PMID- 29936766
TI - [Diagnostic value of protein markers in plasma exosomes of lung squamous cell
carcinoma].
AB - Objective: To investigate the tumor-associated protein molecules carried by
plasma exosomes of patients with lung squamous cell carcinoma before treatment
and analyze their value as clinical markers. Methods: Exosomes from 2 patients
with lung squamous cell carcinoma before treatment and 2 healthy controls were
collected by ultracentrifugation. Proteomics was applied to analyze the protein
expression profiles of exosomes. Candidate molecules were verified in another 30
exosomes samples from lung squamous cell carcinoma and healthy controls using
enzyme-linked immunosorbent assay (ELISA). Results: Electron microscopy and
particle-counting assay showed that high-quality exosomes were collected. The
number of exosomes distributed from 45 to 135 nm in 2 cases of lung cancer
patients were 7.89*10(11)/ml and 9.71*10(11)/ml, respectively, significantly
higher than 2.76*10(11)/ml and 1.41*10(11)/ml in healthy controls. Proteomic
analysis showed that proteins of exosomes in lung squamous cell carcinoma
patients were very different from those of healthy controls, and some proteins
are related to important functions in tumor progression. 14-3-3zeta from exosomes
was selected and further verified as a marker, and the area under the receiver
operating characteristic curve (ROC) was 0.68. The sensitivity and specificity of
14-3-3 zeta from exosomes were 60.0% and 80.0%, respectively, suggested that it
could be used as a diagnostic marker for lung squamous cell carcinoma.
Conclusion: The exosome counts in plasma and the protein molecules from exosomes,
such as 14-3-3zeta, are closely related to the tumorigenesis, which can be used
to assist clinical diagnosis of lung squamous cell carcinoma patients.
PMID- 29936767
TI - [The application of conventional smears and liquid-based cytologic slides of
lymphatic metastasis specimens of lung adenocarcinoma acquired by fine needle
aspiration to detect the expression of anaplastic lymphoma kinase protein].
AB - Objective: To explore the feasibility of conventional smears and liquid-based
cytologic slides of lymphatic metastasis specimens of lung adenocarcinoma
acquired by fine needle aspiration cytology (FNAC) to detect the expression of
anaplastic lymphoma kinase (ALK/D5F3) by immunocytochemistry (ICC) analysis.
Methods: The lymphatic metastasis specimens of 147 lung adenocarcinoma, including
100 liquid-based cytologic slides and 47 conventional smears, were collected in
this study. ALK fusion protein was detected by Roche Ventana ICC technology,
which was compared with the ALK fusion gene assessed by fluorescence in situ
hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR).
Results: The positive rate of ALK (D5F3) fusion protein in advanced lung
adenocarcinoma acquired by FNAC was 11.6% (17/147), and 10.6% (5/47) and 12.0%
(12/100) were reached in conventional smears and liquid-based cytologic slides,
respectively.Among 147 cases, 57 cases including 17 positive cases and 40
negative cases were verified by RT-PCR and FISH. The whole coincidence rate
reached 96.5% (55/57). The sensitivity and specificity of ALK (D5F3) fusion
protein detected in lung adenocarcinoma acquired by FNAC were 94.1% (16/17) and
97.5% (39/40), respectively. The sensitivity and specificity were both 100% (5/5
of sensitivity and 10/10 of specificity) in conventional smears, while 91.7%
(11/12) and 96.7% (29/30) in liquid-based cytologic slides. Conclusion:
Conventional smears and liquid-based cytologic slides of FNAC samples can be used
to perform ICC analysis of ALK (D5F3) expression in advanced lung adenocarcinoma,
especially for patients who have no opportunity for surgery or whose resected
samples are difficult to form cell block.
PMID- 29936768
TI - [Analysis of preoperative predictive factors and clinical characteristics in
patients with parathyroid carcinoma].
AB - Objective: To evaluate the clinical characteristics and preoperative predictive
factors in patients with parathyroid carcinoma. Methods: From January 2010 to
December 2016, 150 patients with pathologically and biochemically confirmed
primary hyperparathyroidism were enrolled in this study. The clinical data were
reviewed to define 28 cases of parathyroid hyperplasia, 14 cases of parathyroid
carcinoma (PC), and 108 cases of parathyroid adenoma (PA). The clinical
characteristics between PC and PA group were compared and analyzed to explore
predictive factors for PC. Results: Patients in PC group were significantly
younger than those in PA group (47.9+/-13.9 vs 57.2+/-14.6 years, P=0.026). The
diameter of tumor in PC group was larger than that in PA group (3.6+/-1.8 vs
2.2+/-1.4 cm, P=0.005). The levels of albumin-corrected serum calcium,
parathyroid hormone (PTH), and alkaline phosphatase (AKP) were all higher in PC
group than those in PA group (3.4+/-0.6 vs 2.9+/-0.3 mmol/l; 1 157.1 vs 201.6
pg/ml; 168 vs 97 IU/L; all P<0.05). PC correlated with age(r=-0.241, P=0.007),
albumin-corrected serum calcium (r=0.324, P<0.001), PTH levels (r=0.301,
P=0.001), serum AKP (r=0.217, P=0.019) and tumor size(r=0.238, P=0.011). Receiver
operator characteristic curve analysis showed that the optimum cut-off values as
follows: albumin-corrected serum calcium 3.15 mmol/L, serum PTH concentration 1
011 pg/ml and tumor diameter 3.35 cm. These indicators can be helpful in the
preoperative diagnosis of PC. Conclusions: Patients with PC were younger than the
patients with PA. Albumin-corrected serum calcium, serum PTH concentration, and
tumor diameter can be helpful in preoperative diagnosis of PC.
PMID- 29936769
TI - [Genetic variations in MLH3 and MSH2 genes are associated with the sensitivity
and prognosis in locally advanced rectal cancer patients receiving preoperative
chemoradiotherapy].
AB - Objective: To investigate the associations between genetic variations in DNA
mismatch repair genes and sensitivity as well as prognosis to preoperative
chemoradiotherapy in patients with locally advanced rectal cancer. Methods:
Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3
and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with
locally advanced rectal cancer who received preoperative chemoradiotherapy. The
associations between genotypes and response to capecitabine-based neoadjuvant
chemoradiotherapy (nCRT) were measured by odds ratios (ORs) and 95% confidence
intervals (CIs), adjusted for sex, age, clinical stages and karnofsky performance
score (KPS) by unconditional logistic regression model. The survival analyses
were performed by the hazard ratios (HRs) and 95% CIs by Cox proportional
regression model. Results: Among 146 cases, 64 patients were nCRT responders with
a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were
associated with the sensitivity to preoperative chemoradiotherapy. Compared with
the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes
was 0.42 (95% CI: 0.19-0.91; P=0.029). Moreover, for rs13019654, the adjusted OR
for patients with the GT or TT genotypes was 0.49 (95% CI: 0.24-0.98; P=0.047)
than those with GG genotype. The remaining 12 SNPs, including rs1540354,
rs4026175, rs1981929, rs2042649, rs2303428, rs3771273, rs4608577, rs4952887,
rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly
associated with therapeutic response to preoperative chemoradiotherapy.
Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall
survival time in locally advanced rectal cancer (HR=0.44, 95% CI: 0.20-0.96,
P=0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were
associated with shorter overall survival time (HR=1.74, 95% CI: 1.06-2.84,
P=0.028; HR=1.64, 95% CI: 1.01-2.66, P=0.046; HR=1.71, 95% CI: 1.01-2.91,
P=0.047, respectively). The remaining 10 SNPs, including rs1540354, rs4026175,
rs1981929, rs2042649, rs2303428, rs4608577, rs4952887, rs6544991, rs6544997 and
rs13019654, were not significantly associated with prognosis. Conclusions:
Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the
nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and
rs10191478 may predict prognosis in patients with locally advanced rectal cancer
who received preoperative chemoradiotherapy. Therefore, these SNPs could be used
as potential genetic markers in the personalized therapy of rectal cancer.
PMID- 29936770
TI - [Clinical application value of combined detection of serum miR-378 and miR-21 in
gastric cancer].
AB - Objective: To investigate the clinical value of combined detection of serum miR
378 and miR-21 in gastric cancer (GC). Methods: Eighty-seven patients with GC and
78 patients with colorectal cancer(CRC) from National Cancer Center/Cancer
Hospital, Chinese Academy of Medical Sciences were selected, 83 individuals
undergoing healthy physical examination were selected as the healthy controls.
The levels of serum miR-378 and miR-21 were detected by quantitative real-time
PCR (RT-qPCR) (result data were transformed as log2 for analysis). Results:
Relative expression levels of miR-378 in the serum were -1.24, -3.25 and -2.73 in
healthy controls, GC and CRC patients, respectively. Compared with the healthy
controls, the levels of serum miR-378 were significantly decreased in GC and CRC
patients (both P<0.05). Relative expression levels of miR-21 in the serum were
0.11, 2.34 and 2.47 in healthy controls, GC and CRC patients, respectively.
Compared with the healthy controls, the levels of serum miR-21 were significantly
up-regulated in GC and CRC patients (both P<0.05). Moreover, the serum level of
miR-378 in GC patients was inversely associated with tumor clinical stage
(P<0.05). However, the level of miR-21 showed no significant differences among
patients with different clinical and pathological characteristics (all P>0.05).
The area under the receiver operating characteristic curve (AUC), sensitivity and
specificity of miRNA-378 to diagnose GC was 0.770, 82.0% and 66.0%, respectively,
and were 0.900, 85.0%, and 88.0% of miR-21, respectively. The AUC, sensitivity
and specificity of combined detection of serum miR-378 and miR-21 to diagnose GC
were 0.930, 92.0% and 87.0%, respectively, while the AUC of combined detection of
serum CEA and CA-199 was 0.767, the AUC of combined all of the four factors was
0.946. Conclusion: The combined detection of serum miR-378 and miR-21 have a
certain effect on diagnosis of GC.
PMID- 29936771
TI - [Prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in locally
advanced non-small cell lung cancer patients treated with thoracic radiation].
AB - Objective: The aim of this retrospective study was to evaluate the prognostic
significance of pretreatment Neutrophil-to-Lymphocyte Ratio(NLR) in locally
advanced non-small cell lung cancer(NSCLC) patients treated with thoracic
radiotherapy. Methods: We retrospectively analyze 420 patients who received
thoracic radiotherapy alone, sequential chemoraiotherapy or concurrent
chemoradiotherapy for locally advanced stage NSCLC from January 2007 to December
2010 of our hospital. The patients were divided into two groups (high NLR group
and low NLR group) with appropriate cutoff point using the receiver operating
characteristic (ROC) curve method. The survival curve was established by Kaplan
Meier method. The Log-rank test was used to compare the survival of the two NLR
groups and the multivariate analysis was carried out by Cox regression model.
Results: Among the 420 patients, 99 received radiotherapy alone, 139 received
sequential chemoradiotherapy and 182 received concurrent chemoradiotherapy. 345
patients died and 75 were still alive. The median follow-up time was 5.2 years
and the median overall survival was 22 months. The cut-off value of pretreatment
NLR was 2.1. The 5-year PFS and OS rates in high NLR group and low NLR group were
10.6% vs 15.7% (P=0.033) and 15.5% vs 22.7% (P=0.012). Multivariate analysis
confirmed that pretreatment NLR (hazard ratio 1.06, P=0.041) was independent
prognostic factor of OS. Conclusions: Our study revealed that the pretreatment
NLR is the independent prognostic factor of OS in patients with locally advanced
stage NSCLC treated with thoracic radiotherapy. However, NLR is still greatly
influenced by patient's condition and treatment which needs further research.
PMID- 29936772
TI - [Clinical characteristics and prognostic analyses of 87 patients with pulmonary
mucoepidermoid carcinoma].
AB - Objective: To investigate the clinicopathological characteristics, therapy and
prognosis of patients with pulmonary mucoepidermoid carcinoma. Methods: The
clinical data of 87 patients diagnosed as pulmonary mucoepidermoid carcinoma at
The First Affiliated Hospital of Zhengzhou University from April 2011 to May 2016
were retrospectively analyzed. The clinicopathological features were summarized
and the prognoses were analyzed. Results: Among the 87 patients with lung
mucoepidermoid carcinoma, 53 were male and 34 were female, the gender ratio
between men and women was 1.56?1.The ages of patients were from 16 to 79 years
and the median age was 52.5 years. Seventeen cases were diagnosed as stage I, 28
cases were stage II, 26 cases were stage III, 16 cases were stage IV.Thirty-six
patients were examined by immunohistochemistry, of which 29 cases were
cytokeratin (CK) 5/6 positive, 29 cases were CK7 positive, 10 cases were CK
positive, 28 cases were p63 positive, 14 cases were p40 positive, 17 cases were
thyroid transcription factor-1 (TTF-1) positive, 11 cases were NapsinA positive,
2 cases were epithelial membrane antigen (EMA) positive, 4 cases were CK8/18
positive, 3 cases were surfactant proteins A (SPA) positive, 1 case was CAM5.2
positive and 1 case was CK14 positive. Among the 87 patients, 34 cases were
treated by operation alone, 23 cases were treated by operation combined with
chemotherapy, 5 cases were treated by radiotherapy combined with chemotherapy, 14
cases were treated by chemotherapy alone, 2 cases were treated by particle
implantation combined with chemotherapy, 2 cases were treated by local
radiofrequency hyperthermia combined with chemotherapy, and 7 cases without
special treatment.Five patients with brain metastasis were treated with cerebral
radiotherapy combined with sequential chemotherapy. The 1-year, 2-year and 5-year
survival rates of 87 patients were 90.7%, 81.6% and 46.3%, respectively. The
median survival time was 60 months. The prognoses of patients with lung
mucoepidermoid carcinoma were related with the clinical stage, smoking and
operative therapy (all P<0.05). Conclusions: The age distribution of patients
with pulmonary mucoepidermoid is a wide range, the incidence of male is higher
than that of female. The diagnosis of pulmonary mucoepidermoid carcinoma mainly
relies on the morphological diagnosis and the immunohistochemical detection is
non-specific. The prognoses of patients with lung mucoepidermoid carcinoma are
related with clinical stage, smoking and operative therapy. For patients who are
inoperable and with single distant metastasis, local radiotherapy, other local
treatment and chemotherapy can significantly improve their prognoses.
PMID- 29936773
TI - [Retrospective analysis of the clinical features and prognostic factors of 370
patients with advanced-stage diffuse large B-cell lymphoma].
AB - Objective: The clinical features and prognosis of diffuse large B-cell lymphoma
(DLBCL) were analyzed to optimize the treatment. Methods: We retrospectively
collected the clinical data of patients with advanced-stage DLBCL from January
2006 to December 2012 in National Cancer Center/Cancer Hospital. The demographic
characteristics, clinical stage, histological diagnosis, treatment and prognostic
characteristics of these patients were analyzed. Results: A total of 370 patients
with median age of 55 years old were recruited in the study. The male-to-female
ratio was 1.3?1. Among the 361 patients who underwent therapy, 280 cases received
chemotherapy alone, 65 cases received chemoradiotherapy, and 16 cases received
chemotherapy combined with autologous hematopoietic stem cell transplantation
(AHSCT). The median follow-up period was 89 months, the 5-year overall survival
(OS) rate of the entire cohort was 42.9%. The 5-year OS rate of chemotherapy
alone, chemoradiotherapy and chemotherapy combined with AHSCT were 36.8%, 58.5%,
87.5%, respectively. The 5-year OS rate were significantly different between
chemoradiotherapy and chemotherapy alone (P=0.001), and between chemotherapy
combined with AHSCT and chemoradiotherapy (P=0.040). Univariate analysis showed
that the age, Eastern Cooperative Oncology Group performance status (ECOG PS)
score, Ann Arbor stage, B symptom, bulky disease, number of extranodal sites, Ki
67 index, lactate dehydrogenase (LDH), beta2-microglobulin (beta2-MG),
international prognostic index (IPI), therapeutic manner and chemotherapy
combined with rituximab were significantly associated with the prognosis of
advanced DLBCL patients (all P<0.05). Multivariate analysis demonstrated that the
age >60 years, Ann Arbor stage IV, with B symptom, with bulky disease, ECOG
PS>=1, Ki-67 index > 90%, CD5 expression, up-regulation of serum LDH and beta2
MG, and chemotherapy without rituximab were related with the poor prognosis of
patients with advanced-stage DLBCL (all P<0.05). Conclusions: Chemotherapy
combined with rituximab can improve the outcome of patients with advanced-stage
DLBCL. The age, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index, CD5
expression, LDH, beta2-MG and chemotherapy combined with rituximab are associated
with the prognosis of these patients.
PMID- 29936774
TI - [Curative effect analysis of postoperative concurrent chemoradiotherapy on early
stage cervical cancer patients with intermediate-risk factors].
AB - Objective: To compare the curative effect of postoperative concurrent
chemoradiotherapy (CCRT) and radiation therapy (RT) alone on early-stage cervical
cancer patients with intermediate-risk factors. Methods: Clinical data of
patients with early stage (IB-IIA) cervical cancer who underwent radical
hysterectomy and pelvic lymphadenectomy in Zhejiang Cancer Hospital between
January 2008 and December 2011 were retrospectively analyzed. Cervical squamous
cell carcinoma patients with more than two intermediate-risk factors, including
lymphatic vascular infiltration, depth of cervical stromal infiltration >1/2 cm
or tumor size >4 cm, were screened. Among them, 80 patients were divided into the
RT group, 137 patients were divided into the CCRT group. The survivals of these
patients were analyzed. Results: At the end of the follow-up period, a total of
22 patients were dead, one patient was alive with neoplasm. There were 23
patients who occurred recurrence/ metastasis, 14 of them were in the RT group and
9 were in the CCRT group. The 5-year progression free survival (PFS) and 5-year
overall survival (OS) rate of the entire cohort were 89.9% and 89.8%,
respectively. The 5-year PFS rate of RT group was 82.4%, the 5-year PFS rate of
CCRT group was 94.1%, and the difference between the two groups was statistically
significant (P=0.013). The 5-year OS rate of RT group was 85.1%, the 5-year OS
rate of CCRT group was 92.7%, and the difference between the two groups was
statistically significant (P=0.049). Univariate analysis showed that therapeutic
modality was associated with the 5-year DFS and OS of early-stage cervical cancer
patients with intermediate-risk factors (P<0.05). The results of multivariate
analysis showed that therapeutic modality was an independent prognostic factor of
favorable PFS (RR=3.741, 95% CI: 1.506-9.289, P=0.004) and OS (RR=2.754,
95%CI=1.143-6.637, P=0.024). Neither of the two groups occurred severe anemia.
However, the incidence of mild and moderate anemia in the CCRT group was higher
than that of RT group (P<0.001). The incidence of leukocytopenia severer than
grade III in the CCRT group was significantly higher than that of RT group
(P<0.001). However, the patients could recover quickly with the treatment of
granulocyte colony-stimulating factor. Conclusion: Postoperative CCRT improves
the survival of early stage cervical cancer patients with two or more
intermediate-risk factors.
PMID- 29936775
TI - [The caregiver burden and related factors on quality of life among caregivers for
patients with lung cancer].
AB - Objective: To explore the influence of caregiver burden on quality of life among
caregivers for patients with lung cancer in Beijing. Methods: From August to
October in 2017, 336 caregivers for patients with primary lung cancer from a
large tertiary hospital were recruited to this survey by convenient sampling
method. The Caregiver Reaction Assessment (CRA) and the WHO Quality of Life-BREF
(WHOQOL-BREF) Instruments were used to evaluate the caregiver burden and quality
of life. The demographic characteristics were evaluated using Pearson chi-square
or Fisher's exact tests. In addition, using the 4 dimensions of quality of life
scale as the dependent variables while the 5 dimensions of caregiver burden and
demographic variables as the explanatory variables, we conducted the multiple
linear stepwise regression analysis (the defaults were 0.15 for FORWARD and
BACKWARD). Results: The scores of family caregivers' esteem, impact on schedule,
impact on finances, impact on health and lack of family support were 4.30+/
0.47,3.55+/-0.74,3.10+/-0.91,2.60+/-0.78,2.32+/-0.73, respectively. Regression
results showed that demographic factors, including marriage, occupation and
relationship with patients and impact on health, caregivers' esteem and impact on
finances dimensions of caregiver burden were the factors which influenced the
quality of life of caregivers. Conclusions: The caregiver burden in patients with
lung cancer is mainly focused on impact on schedule and finances. Impact on
health, finances and caregivers' esteem (seven items were reverse-scored) are
significantly negatively correlated with quality of life of caregivers.
PMID- 29936776
TI - [Ovarian metastasis of small cell lung cancer from left upper lobe: a case
report].
PMID- 29936777
TI - [Association between high risk human papillomavirus DNA load and cervical lesions
in different infection status].
AB - Objective: To explore the relationship between high risk HPV (HR-HPV) DNA load
and cervical lesions in HR-HPV single/ multiple infections. Methods: Two thousand
six hundred and forty-six women from Shanxi, Henan and Xinjiang were recruited
into a cervical cancer screening program. Cervical exfoliated cell specimens
collected from all of the participants were detected by hybrid capture II (HC2),
cytological diagnosis was performed according to the Bethesda System, and
pathological diagnosis was interpreted using cervical intraepithelial neoplasia
(CIN) terminology.Totally 571 cervical specimens were selected and retested to
ascertain the HPV types and single/ multiple infections by liner array, a PCR
based method. Semi-quantitative result of HR-HPV DNA load (pg/ml) was estimated
by HR HC2.According to the taxonomy of "International Human Papillomavirus
Reference Center" , 13 HR-HPVs, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52,
56, 58, 59 and 68, which could be detected by HR HC2 were divided into 4
subgroups. Results: The positive rate of HR-HPV in normal cervix (436 cases),
CIN1 (88 cases), CIN2+ (47 cases) group were 29.82%, 85.23% and 100%,
respectively. The overall prevalence and median viral load increased coordinating
with the pathological degree of cervical lesions (P<0.001). The positive rate and
viral load of single infection with HR-HPV belongs to alpha9 species increased
coordinating with the pathological degree of cervical lesions (P<0.05). The viral
load of single infection with HR-HPV belongs to alpha7 species in CIN1 group was
higher than those of normal group and CIN2+ group, but without statistical
significance (P=0.130). The viral load of multiple infections in CIN1 group was
559.13 pg/ml, significantly higher than 37.73 pg/ml of normal histology
(P=0.025), but without significant difference of 332.91 pg/ml of CIN2+ group
(P=0.790). The median viral load of HPV single infection in CIN1 group was 167.93
pg/ml, significantly lower than 559.73 pg/ml of multiple infections (P=0.044).
The incidence of co-infection with HR-HPVs belong to alpha9 species was 80.56%,
dominated in all patterns of multiple infections and their median viral load
increased coordinating with the pathological degree of cervical lesions, but
without significant difference (P>0.05). The incidence of co-infection with HR
HPVs belong to alpha7 species was 66.67%, their median viral load in CIN1 group
was higher than that of CIN2+ group, but without statistical significance
(P>0.05). Conclusions: Viral loads of single/ multiple infections with HR-HPVs
belong to different species show different tendencies coordinating with the
pathological degree of cervical lesions. Women with high grade of cervical lesion
were dominantly infected with high viral load of HR-HPVs belong to alpha9
species, and the viral load of multiple infections is higher than that of single
infection in low grade of cervical lesion.
PMID- 29936778
TI - Atypical presentation of amniotic fluid embolism in liver and colon.
PMID- 29936779
TI - Joint Spatio-Temporal Shared Component Model with an Application in Iran Cancer
Data
AB - Background: Among the proposals for joint disease mapping, the shared component
model has become morepopular. Another advance to strengthen inference of disease
data is the extension of purely spatial models to includetime aspect. We aim to
combine the idea of multivariate shared components with spatio-temporal modelling
in a jointdisease mapping model and apply it for incidence rates of seven
prevalent cancers in Iran which together account forapproximately 50% of all
cancers. Methods: In the proposed model, each component is shared by different
subsetsof diseases, spatial and temporal trends are considered for each
component, and the relative weight of these trends foreach component for each
relevant disease can be estimated. Results: For esophagus and stomach cancers the
Northernprovinces was the area of high risk. For colorectal cancer Gilan, Semnan,
Fars, Isfahan, Yazd and East-Azerbaijanwere the highest risk provinces. For
bladder and lung cancer, the northwest were the highest risk area. For prostate
andbreast cancers, Isfahan, Yazd, Fars, Tehran, Semnan, Mazandaran and Khorasane
Razavi were the highest risk part.The smoking component, shared by esophagus,
stomach, bladder and lung, had more effect in Gilan, Mazandaran,Chaharmahal and
Bakhtiari, Kohgilouyeh and Boyerahmad, Ardebil and Tehran provinces, in turn. For
overweightand obesity component, shared by esophagus, colorectal, prostate and
breast cancers the largest effect was found forTehran, Khorasane-Razavi, Semnan,
Yazd, Isfahan, Fars, Mazandaran and Gilan, in turn. For low physical
activitycomponent, shared by colorectal and breast cancers North-Khorasan,
Ardebil, Golestan, Ilam, Khorasane-Razavi andSouth-Khorasan had the largest
effects, in turn. The smoking component is significantly more important for
stomachthan for esophagus, bladder and lung. The overweight and obesity had
significantly more effect for colorectal than ofesophagus cancer. Conclusions:
The presented model is a valuable model to model geographical and temporal
variationamong diseases and has some interesting potential features and benefits
over other joint models.
PMID- 29936780
TI - Challenges in Indian Women's Readiness to Quit Smokeless Tobacco Use
AB - Introduction: In India, there are few cessation programs for women smokeless
tobacco (SLT) users who want to quit.This paper uses Fishbein's IM model to
identify women SLT users' challenges to quitting and multilevel correlates
of"readiness to quit". Methods: A survey of SLT use among women of reproductive
age was conducted in 2010-13 in anurban slum community of Mumbai with a
representative sample of 409 married women aged 18 to 40 years using at leastone
type of SLT daily. Data were analyzed using frequencies, bivariate statistics and
logistic regression. Results: Socialinfluences to continue SLT use included
husband's use (71%), family influence and positive beliefs and norms about
use.Pressure to quit from significant others influenced past quit attempts but
media had no effect on reported behavior. Fourgroups represented different
readiness to quit statues based on intention to quit and past quit/reduce
attempts. Seventeenpercent had no intention of quitting or reducing; their
husbands were more likely to be tobacco users. Half of (52%)the sample had
attempted to quit/reduce tobacco and intended to do so in the future. These women
were depressed.Fifteen percent had tried to quit but did not intend to again.
Correlates were positive beliefs and norms about SLT andwithdrawal symptoms.
Conclusions: Cessation programs should be made available to women, addressing
correlates ofwomen's readiness to quit statuses. Results suggest the need for
more complex social/contextual approaches to sustainedcessation of SLT use
including addressing depression and withdrawal, improved media messages and
campaigns tailoredto women, and support from family members.
PMID- 29936781
TI - Comparative Analysis of Modified Liquid-Based Cytology and CytoRich Red
Preparation in Assessment of Serous Effusionfor Cancer Diagnosis
AB - Objective: We aimed to compare the cytomorphological diagnosis in serous effusion
and quality of backgroundbetween modified liquid-based cytology (modified-LBC)
and CytoRich Red (CRR) preservative. Methods: We usedan experimental study
design: 110 fresh serous effusions were received from 50 cases negative for
malignant effusionsand 60 cases positive for malignant effusions. All fresh
serous effusions were processed using both the CRR solutionand the modified-LBC
preparation. Blind sample slides were interpreted for cytomorphological diagnosis
and thequality of background by 2 cytotechnologists. Result: All cases had the
same diagnosis irrespective of the method.There was no statistically significant
difference in the cytological diagnosis between the CRR and modified
LBCpreparations (p>0.999). The quality of the background smear for the CRR
preparation was clean (54%), moderate in42%, and poor in 4%. By comparison, the
modified-LBC preparation was clean in 46%, moderate in 47%, and poor in7%. The
difference between the quality of background smears between the two methods was
not statistically significant(p= 0.527). Conclusion: There was no statistically
significant difference in the diagnosis or quality of backgroundbetween CRR and
modified-LBC preparations. The serous effusion specimen prepared by modified-LBC
solution wasless expensive than CRR. The modified-LBC could be an alternative
preparation when commercial preparations aretoo expensive.
PMID- 29936782
TI - 10 Year Biochemical Failure Free Survival of Men with CD82 Positive Primary
Circulating Prostate Cells Treated by Radical Prostatectomy
AB - Objective: The biological characteristics of circulating prostate cells (CPCs)
are probably more important than theirmere presence. CD82 is a tumor suppressor,
we present the outcome of radical prostatectomy (RP) in men with CD82positive
CPCs. Methods and Patients: consecutive men treated with RP were studied, age,
total PSA, Gleason, stage, thepresence of extra-capsular extension, positive
surgical margens and infiltration of the seminal vesicles and lymph nodeswere
registered. Biochemical failure was defined as a PSA >0.2ng/ml. Immediately
before the RP, 8ml of venous bloodwas taken to detect CPCs. Mononuclear cells
were separated using differential gel centrifugation and CPCs identifiedusing
immunocytochemistry with anti-PSA and anti-CD82. The men were divided into three
groups; 1) CPC (-), 2)CPC (+) CD82 (+) and 3) CPC (+) CD82 (-). The groups were
compared with respect to clinical-pathological findingsand biochemical free
survival using Kaplan Meier and Cox regression models. Results: 285 men, mean age
65.9 yearsparticipated, 61 (21%) were CPC (-); 57 (20%) were CPC (+) CD82 (+) and
167 (59%) were CPC (+) CD82 (-). Group1 had low grade small volume cancer, in
Group 2, low grade but a larger volume than Group 1 and Group 3 high gradecancer.
Kaplan Meier biochemical free survival curves at 36, 60 and 120 months were;
Group 1 98%, 96% and 90%;for Group 2 93%, 93% and 69% and for Group 3 62%, 44%
and 16% respectively. Conclusions: Kaplan Meier survivalcurves for Group 1 and
Group 2 were similar, although Group 2 men had higher PSA values, more advanced
stagingbut a similar Gleason score. Group 3 men had a worse prognosis. The
results support that biological characteristics ofCPCs are more important than
their mere presence identifying men with a high risk of biochemical failure.
PMID- 29936783
TI - Re-Expression of Bone Marrow Proteoglycan-2 by 5-Azacytidine is associated with
STAT3 Inactivation and SensitivityResponse to Imatinib in Resistant CML Cells
AB - Background: Epigenetic silencing of tumor suppressor genes (TSG) is involved in
development andprogression of cancers. Re-expression of TSG is inversely
proportionate with STAT3 signaling pathways.Demethylation of DNA by 5-Azacytidine
(5-Aza) results in re-expression of silenced TSG. Forced expression ofPRG2 by 5
Aza induced apoptosis in cancer cells. Imatinib is a tyrosine kinase inhibitor
that potently inhibits BCR/ABL tyrosine kinase resulting in hematological
remission in CML patients. However, majority of CML patients treatedwith imatinib
would develop resistance under prolonged therapy. Methods: CML cells resistant to
imatinib weretreated with 5-Aza and cytotoxicity of imatinib and apoptosis were
determined by MTS and annexin-V, respectively.Gene expression analysis was
detected by real time-PCR, STATs activity examined using Western blot and
methylationstatus of PRG2 was determined by pyrosequencing analysis. Result:
Expression of PRG2 was significantly higher inK562-R+5-Aza cells compared to K562
and K562-R (p=0.001). Methylation of PRG2 gene was significantly decreasedin K562
R+5-Aza cells compared to other cells (p=0.021). STAT3 was inactivated in K562
R+5-Aza cells which showedhigher sensitivity to imatinib. Conclusion: PRG2 gene
is a TSG and its overexpression might induce sensitivity toimatinib. However,
further studies are required to evaluate the negative regulations of PRG2 on
STAT3 signaling.
PMID- 29936784
TI - Concurrent Chemoradiotherapy for Loco-regionally Advanced Nasopharyngeal
Carcinoma: Treatment Outcomes andPrognostic Factors
AB - Background: We conducted this study to contribute to resolving some controversial
issues on management ofnasopharyngeal carcinoma. Methods: Thirty-two patients
with stage III-IVB nasopharyngeal carcinoma were includedin this retrospective
study. All patients received concurrent chemoradiotherapy with either 3D
conformal radiotherapyor intensity-modulated radiotherapy. We retrospectively
analyzed the survival outcome, prognostic factors for survival,and toxicity
outcome. Results: The 2- and 5-year overall survival rates were 89.9% and 82.6%.
The 2- and 5-yeardistant metastasis-free survival rates were 83.2% and 79.4%. The
2- and 5-year loco-regional recurrence-free survivalrates were 83.3% and 79.5%.
Addition of induction chemotherapy to concurrent chemoradiotherapy did not
improvesurvival outcomes. The survival benefit of intensity-modulated
radiotherapy over 3D conformal radiotherapy was notclear. Intensity-modulated
radiotherapy significantly decreased the development of late toxicities compared
with 3Dconformal radiotherapy. Total RT dose was prognostic factor for overall,
loco-regional recurrence-free, and distantmetastasis-free survival. Temporary RT
interruption was prognostic factor for overall survival. Daily RT dose
wasprognostic factor for distant metastasis-free survival. Conclusions:
Concurrent chemoradiotherapy resulted in highsurvival rates with an acceptable
level of toxicities in patients with loco-regionally advanced nasopharyngeal
carcinoma.To confirm the results of this study, well-designed randomized
prospective trials are warranted.
PMID- 29936785
TI - Comparison Cure Rate Models by DIC Criteria in Breast Cancer Data
AB - Background: One of the malignant tumors is Breast Cancer (BC) that starts in the
cells of breast. There is manymodels for survival analysis of patients such as
Cox PH model, Parametric models etc. But some disease are thatall of patients
will not experience main event then usual survival model is inappropriate. In
addition, In the presence ofcured patients, if researcher can specify
distribution of survival time, usually cure rate models are preferable
toparametric models. Distribution of Survival time can be Weibull, Log normal,
Logistic, Gamma and so. Comparison ofWeibull, Log normal and Logistic
distribution for finding the best distribution of survival time is purpose of
this study.Material and Methods: Among 787 patients with BC by Cancer Research
Center recognized and followed from1985 until 2013. Variables stage of cancer,
age at diagnosis, tumor size and Number of Removed Positive LymphNodes (NRPLN)
for fitting Cure rate model were selected. The best model selected with DIC
criteria. All analysiswere performed using SAS 9.2. Results: Mean (SD) of age was
48.47 (11.49) years and Mean of survival time andMaximum follow up time was 326
and 55.12 months respectively. During following patients, 145 (18.4%)
patientsdied from BC and others survived (censored). Also, 1-year, 5-year and 10
year survival rate was 94, 77 and 56 percentrespectively. Log normal model with
smaller DIC were selected and fitted. All of mentioned variables in the modelwere
significant on cure rate. Conclusion: This study indicated that survival time of
BC followed from Log normaldistribution in the best way.
PMID- 29936786
TI - Mammographic Density Distribution in Ras Al Khaimah (RAK): Relationships with
Demographic and Reproductive Factors
AB - Objective: Mammographic density is an important risk factor for breast cancer and
determines to a large extentmammographic screening efficacy. This study aims to
provide baseline data for mammographic density profiling ofwomen living in Ras Al
Khaimah (RAK) and to identify risk factors associated with high mammographic
density.Methods: A cross-sectional design was used to examine a series of 366
mammography cases. The Breast ImagingReporting and Data System (BI-RADS, 5th
edition) was used to evaluate mammographic density. Pearson'schi-squared, Mann
Whitney U test and multivariate logistic regression were used for statistical
analysis. Results:Most participants (67%) fell into BI-RADS b and c mammographic
density categories. Of the total sample, womenwho were aged <= 45 years (p=0.004,
OR=1.9), weighed <= 71kg (p=<0.0001, OR=4.8), had a body mass index of <= 27kg/m2
(p=<0.0001, OR=5.1) and were of non-Arab descent (p=0.007, OR=1.8) were
significantly more likely to havedenser breast tissue. Adjusted ethnicity
regression analysis showed that Emirati women were significantly less likely
tohave dense breast tissue compared with Western women (p=0.04, OR=0.4). Among
the sample of survey participants,increased odds of having mammographic density
were among women who were full-time workers (p=0.02, OR=2.8),of Christian faith
(p=0.007, OR=4.4), nulliparous (p=0.003, OR=10.8), had three or fewer children
(p=0.03, OR=3.8),and had used oral contraceptives for three years or more
(p=0.01, OR=6.1). Conclusion: This study indicated thatbecause Emirati women have
a low mammographic density profile, screening mammography can be considered as
aneffective early detection imaging modality.
PMID- 29936787
TI - Frequency and Predictors of Axillary Lymph Node Metastases in Iranian Women with
Early Breast Cancer
AB - Background: Axillary lymph node metastasis is the most important predictive
factor for recurrence risk andsurvival in patients with invasive breast
carcinoma. The aim of this study was to determine factors associated
withmetastatic involvement of axillary lymph nodes in Iranian women with early
breast cancer. Methods: This article reportsa retrospective study of 774 patients
with T1-T2 breast cancer who underwent resection of the primary tumor and
axillarystaging by SLNB and/or ALND between 2005 and 2015 at our institution.
Results: Of the 774 patients included in thisstudy, 35.5% (275 cases) had
axillary lymph node involvement at the time of diagnosis. Factors associated with
nodalinvolvement in univariate analyses were tumor size, lymphovascular invasion
(LVI), tumor grade, ER/PR status andHER2 expression. All factors identified with
univariate analyses were entered into a multivariate logistic regressionmodel and
tumor size (OR= 3.01, CI 2.01-4.49, P <0.001), ER/PR positivity (OR = 1.74, CI
1.1.16-2.62, P = 0.007)and presence of LVI (OR = 3.3.8, CI 2.31-4.95, P <0.001)
remained as independent predictors of axillary lymph nodeinvolvement
.Conclusions: In conclusion, the results of this study suggests that positive
hormonal receptor status, LVIand tumor size are predictive factors for ALNM in
Iranian women with early breast cancer.
PMID- 29936788
TI - Diagnostic utility of endobronchial ultrasound features in differentiating
malignant and benign lymph nodes.
AB - Endobronchial ultrasound (EBUS) features have been shown to be useful in
predicting etiology of enlarged malignant lymph nodes. However, there is dearth
of evidence especially from developing countries. We assessed the EBUS
characteristics across various mediastinal and hilar lymphadenopathies. In this
prospective study, all patients with mediastinal and hilar lymphadenopathy on CT
Chest and who were planned for EBUS-FNA (Fine Needle Aspiration) were included.
EBUS features of lymph nodes studied were shape, size, margins, echogenicity,
central hilar structure (CHS), coagulation necrosis sign and colour power doppler
index (CPDI). These were scored and compared between benign and malignant
lymphadenopathies. A total of 86 lymph nodes in 46 patients were prospectively
studied of which 23 (26.7%) were malignant, 27 (31.3%) tuberculosis and 36
(41.8%) sarcoidosis. There was significant difference between malignant and
benign lymph nodes in terms of CHS [central hilar structutre] (p=0.011), margins
(p=0.036) and coagulation necrosis sign (p<0.001). On comparison of features of
malignancy and tuberculosis, there were significant differences in margins
(p=0.016) and coagulation necrosis sign (p 0.001). However, when malignancy and
sarcoidosis was compared, there were differences in echogenicity (p=0.002), CHS
(p=0.009) and coagulation necrosis sign (p<0.001). Only coagulation necrosis sign
was found to be highly consistent with malignant lymph nodes. The other features
cannot be used to distinguish malignant from benign lymph nodes, especially in a
developing country like India where tuberculosis is a common cause of mediastinal
lymphadenopathy.
PMID- 29936789
TI - Psychometric Properties of the Persian Version of the Offspring Cancer Needs
Instrument (OCNI)
AB - Aim: The offspring cancer needs instrument (OCNI) was developed specifically for
assessing unmet psychosocialneeds of adolescents and young adults who have a
parent with cancer. The aim of this study is to examine thepsychometric
properties of the Persian version of this instrument. Methods: For this
methodological study, translationof OCNI into Persian was conducted using
translation and back-translation and revision in line with the developerof the
instrument. Then, face and content validity, construct validity, internal
consistency and stability of the Persianversion of the instrument were examined
with a population of 188 adolescents and young people having a parent withcancer
in five hospitals in Tehran, Iran. Data were analyzed using SPSS version 16 and
LISREL 8.5. Results: The finalPersian version of the instrument demonstrated face
and content validity proven by expert and participant reviews.Confirmatory factor
analysis confirmed construct validity of the instrument and its seven subscales.
Cronbach's alphawas 0.96 for the total instrument and 0.76-0.93 for its seven
subscales. The intraclass correlation coefficient (ICC)calculated to evaluate the
test-retest reliability, was 0.83. Conclusions: The Persian version of OCNI has
acceptablepsychometric properties. It can be used for measuring psychosocial
unmet needs in adolescents and young adults inPersian language populations who
have a parent with cancer.
PMID- 29936790
TI - Characterization and Validation of Hepatocellular Carcinoma (HCC) Xenograft tumor
as a Suitable Liver Cancer Model forPreclinical Mesenchymal Stem Cell Studies
AB - Background: Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer and
the third leading causeof cancer-related death. sorafenib is used as a standard
therapy to treat HCC. mesenchymal stromal cells (MSCs)have also been used to
suppress HCC. Here we investigate the development of a xenograft model of liver
cancer tostudy the homing of hpMSC-GFP cells, tumor kinetics and molecular
characterizations of HCC. Methods: To createxenograft models of HCC, HepG2 cell
lines were inoculated into the flanks of 9 nude mice bilaterally. Animals
werethen divided into three groups: the first group received hpMSC-GFP
systemically, the second received intra-tumoralhpMSC-GFP and the third received
PBS. The first two groups were sacrificed after 72 hours of MSCs injection butthe
third group was followed up for forty days. One tumor from each animal was then
transferred to formalin bufferfor H&E staining and immunohistochemistry analysis
(KI67 and CD34), and the other tumor was used for ex-vivoimaging. Blood samples
were taken from all subjects before sacrificing them. Results: Histopathological
fidelity ofheterotopic HePG2 xenograft models to human HCC tumors was
demonstrated. Biochemical evaluation suggestedthe health of the animal's liver
and kidneys. Ex-vivo imaging illustrated homing of more hpMSC-GFP cells in
tumortissues derived from the group receiving intra-tumoral hpMSC-GFP.
Conclusion: A standard method was used toinoculate tumor cells and the
intervention was shown to be safe to liver and kidneys. Local injection of MSCs
can beused as cell therapy to fight neoplasms.
PMID- 29936791
TI - Lack of Association between Oral Lichen Planus and Hepatitis B and C Virus
Infection - a Report from Southeast Iran
AB - Background: Oral lichen planus (OLP) is a chronic autoimmune disease with an
unknown etiology. Dentistsare usually the first medical practitioners to diagnose
this condition although it also affects body parts other thanthe oral mucosa.
Several studies have reported an association between the OLP and hepatitis B and
C infections.This study aimed to determine the prevalence of hepatitis B virus
(HBV) antigen and hepatitis C virus (HCV) antibodiesin patients with OLP compared
with healthy controls. Methods: In this case-control study, 50 patients with
clinicaland histopathological characteristics of OLP, and 50 age- and sex-matched
healthy controls supplied serum samples(5 mL) for evaluation by ELISA. Data were
analyzed using SPSS Software, version 21. Chi-square test was applied
asappropriate. Results: In this study, the 50 patients with OLP (33 females and
17 males) had a mean age of 42.0 +/- 14.5years, and the 50 healthy subjects (33
females and 17 males) a mean age of 41.9 +/- 13.7 years. None demonstrated
anyevidence of HBV antigen or HCV antibodies. Discussion: We could not detect any
association between OLP and viralhepatitis. This could be attributed to a lower
prevalence of hepatitis viruses compared to other countries or genotypicvariation
or other etiological factors contributing in our cases.
PMID- 29936792
TI - Tristetraprolin Overexpression in Gastric Cancer Cells Suppresses PD-L1
Expression and Inhibits Tumor Progression by Enhancing Antitumor Immunity.
AB - The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich
elements in the 3'-untranslated region of messenger RNAs and facilitates rapid
degradation of the target mRNAs. Therefore, it regulates the expression of
multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP
in cancer cells influences cancer progression and predicts poor survival.
Although the functions of TTP on cancer cells have previously been researched,
the mechanism of TTP on the interaction between cancer cells with their
microenvironment remains undiscovered. In this study, we admed to determine the
role of cancer cell TTP during the interaction between tumor and immune cells,
specifically regulatory T cells (Tregs). We evaluate the capability of TTP to
modulate the antitumor immunity of GC and explored the underlying mechanism. The
overexpression of TTP in GC cells dramatically increased peripheral blood
mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased
cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg
development and infiltration. Surprisingly, we found the stabilization of
programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The
PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to
play a pivotal role in Treg development and functional maintenance in immune
system. Taken together, our results suggest the overexpression of TTP in GC cells
not only affects cell survival and apoptosis but also increases PBMLs -mediated
cytotoxicity against GC cells to decelerate tumor progression. Moreover, we
identified PD-L1 as a critical TTP-regulated factor that contributes to
inhibiting antitumor immunity.
PMID- 29936793
TI - Impaired Taste Associative Memory and Memory Enhancement by Feeding Omija in
Parkinson's Disease Fly Model.
AB - Neurodegeneration can result in memory loss in the central nervous system (CNS)
and impairment of taste and smell in the peripheral nervous system (PNS). The
neurodegeneration seen in Parkinson's disease (PD) is characterized by functional
loss of dopaminergic neurons. Recent studies have also found a role for
dopaminergic neurons in regulating taste memory rewards in insects. To
investigate how taste memories and sugar sensitivity can be affected in PD, we
utilized the DJ-1beta mutant fruit fly, DJ-1betaex54 , as a PD model. We
performed binary choice feeding assays, electrophysiology and taste-mediated
memory tests to explore the function of the DJ-1beta gene in terms of sugar
sensitivity as well as associative taste memory. We found that PD flies exhibited
an impaired ability to discriminate sucrose across a range of sugar
concentrations, with normal responses at only very high concentrations of sugar.
They also showed an impairment in associative taste memory. We highlight that the
taste impairment and memory defect in DJ-1betaex54 can be recovered by the
expression of wild-type DJ-1beta gene in the dopaminergic neurons. We also
emphasized the role of dopaminergic neurons in restoring taste memory function.
This impaired memory property of DJ-1betaex54 flies also allows them to be used
as a model system for finding supplementary dietary foods that can improve memory
function. Here we provide evidence that the associative taste memory of both
control and DJ-1betaex54 flies can be enhanced with dietary supplementation of
the medicinal plant, omija.
PMID- 29936794
TI - Fungal diversity of root vegetables and soil rhizosphere collected from organic
and conventional farms in Eastern Poland.
AB - OBJECTIVE: Determination of the concentration and species composition of
filamentous fungi in root vegetables (carrots and red beetroots), and the
adjacent rhizosphere soil, collected on organic and conventional farms in Eastern
Poland. MATERIAL AND METHODS: During the period 2015-2016, a total number of 80
samples of vegetables and 40 samples of soil were examined. From each type of
farm, 20 samples of vegetables and 20 samples of the adjacent soil were examined.
In addition, the study included 20 samples of vegetables from organic farms and
20 samples of vegetables from conventional farms purchased on the markets in the
city of Lublin in Eastern Poland. In order to determine the concentration and
species composition of filamentous fungi, both in vegetables and soil, the method
of plate dilutions on Malt Agar medium (Difco) with chloramphenicol was used. The
study was conducted in two parallel repetitions. Inoculated media were incubated
at the temperature of 30 degrees C for 72 hours, then at room temperature for 72
hours. The species composition of fungal flora was determined using macroscopic
and microscopic methods, with the help of keys and atlases. RESULTS: It was found
that the mean concentration of fungi was higher in vegetables and soil from
conventional farms than in those from organic farms. In the case of carrots and
soil from conventional farms, this concentration was 4.93 and 5.10
log10 CFU g-1, respectively, whereas from organic farms -
respectively, 3.81 and 4.20 log10 CFU g-1. In the case of
beetroots and soil from conventional farms, the mean concentrations were also
higher compared to organic farms - 5.09 vs. 3.93 and 4.95 vs. 4.23
log10 CFU g-1. In the examined vegetables and rhizosphere
soil, 61 species of filamentous fungi were found, of which 12 belonged to the
genus Penicillium, 4 to the genus Fusarium, and 2 species each to the
genera: Aspergillus, Cladosporium and Trichoderma. As many as 28
(45.9%) fungal species that occurred in vegetables and soil are regarded as
pathogenic for humans.
PMID- 29936795
TI - First molecular characterization of Dobrava-Belgrade virus found in Apodemus
flavicollis in Poland.
AB - INTRODUCTION: Dobrava-Belgrade virus (DOBV) is one of the emerging pathogens
which have been reported during the last decades in Europe and have attracted the
attention of researchers. The course of infection among humans may have a varied
course - from the completely asymptomatic to the more severe forms, such as
haemorrhagic fever with renal syndrome (HFRS). DOBV is hosted and carried by
rodents like Apodemus flavicollis or A. agrarius, which occur commonly in Europe.
OBJECTIVE: To-date, orthohantaviruses have been reported in Poland, both in
humans and animals, but detailed country-scale studies have not yet been carried
out. The aim of the study was molecular characterization of a strain which was
found in A. flavicollis in south-eastern Poland. MATERIAL AND METHODS: The
phylogenetic analysis of the first Dobrava-Belgrade virus found in A. flavicollis
in the subcarpathian region of south-eastern Poland, presented in this study, was
performed after virus proliferation in cell culture and sequencing of specific
PCR products. RESULTS: Based on genetic sequences of fragments of three segments
(S, M and L), the isolated virus was assigned to the Dobrava genotype, taking
into consideration the most current classification of the DOBV species.
CONCLUSIONS: The Dobrava-Belgrade virus strain isolated from A. flavicollis in
the subcarpathian region of south-eastern Poland, has been molecularly
characterized and assigned to Dobrava genotype, thereby the occurrence of that
genotype in Poland has been confirmed by molecular techniques.
PMID- 29936796
TI - First detection and molecular characterization of hepatitis E virus in water from
wastewater treatment plants in Portugal.
PMID- 29936797
TI - Tick distribution along animal tracks: implication for preventative medicine.
AB - INTRODUCTION: Tick abundance and the prevalence of the pathogens they carry have
been increasing worldwide in the last decades, and is projected to increase even
further. Despite the fact that problem is global, there still remain many gaps in
the diagnosis and treatment of tick-borne diseases. The best protection from tick
borne pathogens, therefore, is prevention and avoidance of bites. Ticks mobility
is limited so that their spatial distribution is strongly correlated with the
presence of, especially with large mammals. In this study, the hypothesis was
tested that tick abundance is higher on animal tracks in the forests than in
adjacent habitats. This is an important issue because there are still several
human habits and practices that can decrease the zoonoses risk. For example,
during recreation in forest, people should always walk on the paths (including
narrow animal's tracks) instead of wading through bushes. MATERIAL AND METHODS:
Flagging of animal trails and near control transects were performed
simultaneously. Next, collected ticks were counted, sexed and aged. RESULTS: The
abundance of ticks was almost 5-fold (Ixodes ricinus) and 3-fold (Dermacentor
spp.) higher on animal trails than on adjacent control transects. CONCLUSIONS:
The results obtained support the hypothesis that ticks are more abundant on
pathways than in adjacent habitats. Most likely, the pattern emerges because
large mammals, like deer, which are the most important ticks hosts, use forest
paths to move across the landscape and frequently move along the same routes.
This research sends an important public message that these forest trails are
hotspots of disease risk and should be avoided.
PMID- 29936798
TI - New findings of airborne fungal spores in the atmosphere of Havana, Cuba, using
aerobiological non-viable methodology.
AB - INTRODUCTION: Although airborne fungal diversity in tropical countries is known
to be considerable, aerobiological research to-date has identified only a part of
the fungal mycobiota that may have an impact both on human health and on crops.
Previous studies in Havana city identified only 30 genera and 5 spore types;
therefore,new research is required in these latitudes. This study sought to
investigate airborne spore levels in Havana, with a view to learning more about
local fungal diversity and assessing its influence in quantitative terms.
MATERIAL AND METHODS: A Hirst type volumetric sampler was located on the rooftop
of a building 35 meters above ground level, in a busy area of the city. Sampling
was carried out continuously (operating 24hours/day), at 10 L per minute during
the year 2015. The fungal spores were collected on a Melinex tape coated with a
2% silicone solution. The results were expressed as spores per cubic meter
(spores/m3) of air when to referring to daily values, and spores count
if referring to annual value. RESULTS: Fourteen new genera were identified in the
course of volumetric sampling: six produce ascospores and eight conidia.
Morphobiometric characteristics were noted for all genera, and airborne
concentrations were calculated. These genera accounted for 56.4% of relative
fungal frequency over the study year. CONCLUSIONS: Many airbone fungi are primary
causes of both respiratory disease and crop damage. These new findings constitute
a major contribution to Cuba's aerobiological database.
PMID- 29936799
TI - Cat Scratch Disease in a 1.5-year-old girl - Case report.
AB - INTRODUCTION: The paper is a case report presenting Cat Scratch Disease (CSD) in
a 1.5-year- old girl. Bartoneloses, including CSD, are a group of infectious
diseases which are rarely detected, therefore there are no statistical data
concerning the aetiology, and the incidence of CSD noted in Poland is low in
comparison with other European countries. OBJECTIVE: The purpose of the paper is
to discuss several problems related to CSD. MATERIAL AND METHODS: A 1.5-year-old
girl who was seen in hospital for the sparing use of her left arm when crawling.
X-rays showed osteolytic lesions which radiologists described as multi-ocular
cyst or infection. As neither clinical examination nor laboratory investigations
found pathological signs, the patient was followed-up on an ambulant basis.
Repeated x-ray taken 4 weeks later showed increased periosteal proliferation
accompanied by pain. The baby was admitted to the Clinic but additional
investigations found no pathologies. The baby was consulted by a rheumatologist
and haematologist; however, they did not facilitate a definitive diagnosis. As
the baby developed, because of a thickening of the soft tissues on the dorsal
side of the distal epiphisis in the forearm the doctors decided to inspect the
condition operatively. Macroscopic examination found brownish granulated tissue.
Suction drainage was inserted and a tissue sample was tested for aerobic and
anaerobic bacteria, tuberculosis and borelliosis. The test results were negative.
The baby was in good condition, was not pyrexial and suffered from less pain. The
diagnostics was further expanded and the baby tested for yersinia, chlamydia,
tuberculosis and bartonella, i.e. CSD. The postoperative wound healed soon and
radiological bony lesions began to resolve. After a month, we received a positive
bartonella test result, the baby tested positively for Bartonella henselae
IgG class, which confirmed past or active infection of CSD. A repeated test for
B. henselae taken 6 months later showed a lower level of antibodies.
CONCLUSIONS: It should be remembered that CSD, which is an extremely rare
infection, can be diagnosed despite mediocre clinical and radiological
manifestations. Thus, in the case of infections of unexplained aetiology and
mediocre manifestations diagnostics should include testing for Bartonella
henselae.
PMID- 29936800
TI - Assessment of musculoskeltal system pain complaints reported by forestry workers.
AB - INTRODUCTION: According to the European Occupational Diseases Statistics (EODS
2005) diseases related with musculoskeletal disorders occupy the first position
on the obligatory list of occupational diseases. These disorders most frequently
occur in the agriculture-hunting-forestry sector in such countries as: Finland,
Holland, Germany, France and Spain (data: EU-OSHA). MATERIAL AND METHODS: The
study included a selected group of males - 414 forestry workers, employees of the
State Forests, aged 25-65, mean age 48. The control group were 119 office workers
aged 23-64, mean age 45.8. The basic research instrument was a questionnaire
designed by specialists concerning pain complaints occurring in 7 areas of the
motor system: neck, arms, upper and lower back, hips, knees and feet. RESULTS:
The results of the survey showed that in the selected group of forestry workers,
among 7 investigated areas of the motor system, the most frequently reported pain
complaints involved the lower part of the spine (272 persons, 65.7% of the total
number of respondents). In the control group such pain complaints occurred in
55.5% (66) of office workers (p = 0.04). Forestry workers most often described
this pain as permanent, radiating to the leg, or as an acute pain. According to
the frequency of reporting pain, the area of the knees was placed on the second
position (214 foresters; 51.7%). CONCLUSIONS: The work of a forester which
consist, among other things, in relocation on foot or by vehicle over long
distances along an uneven terrain and in various weather conditions, is a risk
factor of the occurrence of musculosceletal disorders concerning the low back and
knees.
PMID- 29936801
TI - Skin and nasal vestibule colonisation by Staphylococcus aureus and its
susceptibility to drugs in atopic dermatitis patients.
AB - INTRODUCTION: Atopic dermatitis (AD) is a chronic and recurrent disease with an
inflammatory background. Genetic and environmental factors are responsible for
the occurrence and development of this dermatosis. OBJECTIVE: The aim of the
study was to assess the frequency of colonisation of the nasal vestibule and
apparently healthy skin by S. aureus, and to assess dermal lesions for
superinfection with S. aureus in AD patients. MATERIAL AND METHODS: The
research was performed on a population of 100 AD patients. Three smears were
collected for microbiological investigations: from the anterior nares, from
apparently healthy skin and from lesioned skin. On collection, the material was
cultured on mediums provided by the bioMerieux and Argenta companies. The strains
were identified and their sensitivity to antibiotics assessed by means of the
Vitek2 system (bioMerieux). RESULTS: S. aureus was present in at least one
location in 90%. 44% presented S. aureus colonization of apparently
healthy skin and within skin lesions. In the case of 23%, this particular
pathogen was detected only in skin lesions, whereas 6% had a positive result
within the area of apparently healthy skin. In total, S. aureus was
detected in the skin of 73%. In 61%, apparently healthy skin had been colonized
with S. aureus, whereas in 81% colonization was proved within the skin
lesions. S. aureus was detected in the nasal vestibule of 85%. Among the
group with S. aureus in their anterior nares, the pathogen was also found
on the skin surface of 77%. CONCLUSIONS: S. aureus colonises skin in most
AD patients. Most AD patients carry S. aureus in their nasal vestibules.
S. aureus does not seem to colonise healthy skin as often as skin lesions
in young people. The vast majority of S. aureus strains were sensitive to
local antibiotics. Most S. aureus strains produced penicillinase.
PMID- 29936802
TI - Anti-inflammatory effect on genes expression after four days of Qigong training
in peripheral mononuclear blood cells in healthy women.
AB - INTRODUCTION: Some studies have shown the influence of Qigong on gene expression
in different cells, but there is little data associated with the influence of
this kind of therapy on genes expression in pheripheral monocellucar blood cells.
OBJECTIVE: The aim of this study was to evaluate changes in the expression of
genes associated with cellular stress response in peripheral mononuclear blood
cells (PMBC) in healthy women. MATERIAL AND METHODS: The experiment took place at
the Japanese Martial Arts Centre "DOJO" in Stara Wies, Poland, conducted over the
course of a 4-day qigong training session. To evaluate the genes effect of this
training, blood samples were taken before and after the training period. This
experiment involved 20 healthy women (aged 56.2+/-9.01, body height 164.8+/-6.5
and mass 65.5+/-8.2). To determine the expression of HSF-1, HSPA1A, NF-kB, IL10
and CCL2 mRNA, 3 ml of venous blood was collected. The blood samples were placed
in tubes allowing for separation (BD Vacutainer CPT TM) before and
after the 4 days of qigong training. Isolated PMBC were used to determine gene
expression using real-time qRT-PCR (quantitative reverse transcription polymerase
chain reaction). RESULTS: Significant decreases in NF-kB and CCL2 mRNA and
increases in IL10, HSF1 and HSPA1A m-RNA were detected after 4 days of qigong
training. The obtained findings suggest that qigong caused a reduction in the
inflammatory and intensified anti-inflammatory gene expression, as well as a
higher expression of HSF-1 and HSPA1A. CONCLUSIONS: The adaptive response to
qigong training was similar to the adaptive response to physical activity and was
detected through gene expression in PMBC. Furthermore, this kind of training is
especially indicated for women because of their higher susceptibility to
psychosocial stress when compared to men.
PMID- 29936803
TI - Pilot study of Ixodes ricinus ticks preference for human ABO blood groups using a
simple in vitro method.
AB - INTRODUCTION AND OBJECTIVES: The existence of a blood group preference for ticks
is a problem widely discussed among the lay public but often neglected by the
scientific community. The Ixodes ricinus tick transmits serious zoonotic
diseases such as Lyme borreliosis, tick encephalitis, or anaplasmosis. The
preventive strategies include vaccination (if available) and individual measures
including the use of repellents and avoidance of risk areas. MATERIAL AND
METHODS: Since this topic is relatively neglected in the scientific literature, a
simple in vitro method was used. Ticks used in this study were collected
in the suburban region of Ruda in Brno, Czech Republic. One hundred active nymphs
of the collected ticks were tested for preferences for blood groups, using Petri
dishes and blood samples from volunteers. To demonstrate the threat of ticks and
the diseases they transmit, the positivity of one of the most abundant zoonosis,
Lyme borreliosis, was tested using dark-field microscopy. RESULTS: The results
obtained showed that the examined ticks were attracted most by blood group A,
whereas the least preferred was group B, which was proved statistically (p
<0.05). The mean positivity of collected ticks for the presence of spirochaetes
was 9.35%. CONCLUSIONS: The results indicate that the host selection of ticks may
be influenced by the physiological or biochemical profile of an individual, such
as their blood group. This means that a blood group of an individual can be one
of the factors that increase the risk of tick bite and the transmission of
dangerous diseases and thus must not be underestimated.
PMID- 29936804
TI - Chlamydiosis in farmed chickens in Slovakia and zoonotic risk for humans.
AB - INTRODUCTION: Chlamydia psittaci is an obligate intracellular Gram
negative bacterium causing respiratory disease (chlamydiosis) or asymptomatic
carriage in poultry. In humans, it is a zoonotic agent of ornithosis/psittacosis.
Due to low awareness of the disease and variable clinical presentation,
psittacosis is often remains unrecognised as such by general practitioners.
Zoonotic transfer occurs through inhalation of contaminated aerosols, and
originates from feathers, faecal material and respiratory tract exudates.
OBJECTIVE: The aim of this study was to investigate chickens for the presence of
Chlamydia sp. from pharyngeal and cloacal swabs and review the zoonotic
risk for humans. MATERIAL AND METHODS: 138 clinically healthy chickens from farms
in Slovakia were examined for the presence of Chlamydia sp. The age of the
chickens was 6 months. Two different samples were used - pharyngeal swabs and
cloacal swabs. Each sample was examined by the molecular PCR method, and in the
case of a positive result the identity of the obtained sequences was examined by
a BLAST search. RESULTS: Of the total number of 276 examined samples from 138
chickens, 19 (6.9%) showed positivity for C. psittaci infection, 12 (8.7%)
which were positive from pharyngeal swabs and 7 (5.1%) from cloacal swabs. None
of the chickens were positive in both samples. Phylogenetic examination of the 19
isolates identified in the study, based on the 23S rRNA gene sequence, revealed
that the isolates obtained were identical with C. psittaci, and
genetically very close to genotypes B and genotype E. CONCLUSIONS: C.
psittaci infections are apparently emerging in chickens. Chicken-processing
plant employees should be considered a risk group for human psittacosis. There is
a need for higher awareness and for efficient risk assessment and management.
PMID- 29936805
TI - Satisfaction with life among women with breast cancer - selected demographic and
social factors.
AB - OBJECTIVE: The aim of the study was evaluation of satisfaction with life among
women ill with breast cancer, with consideration of selected demographic and
social factors. MATERIAL AND METHODS: In the study participated 121 patients from
the Sub-Carpathian Oncology Centre in Brzozow, Poland, who had undergone surgical
treatment due to breast cancer. The method of a diagnostic survey was used. The
research instruments were an author-constructed questionnaire and the
Satisfaction with Life Scale. RESULTS: Women who received surgical treatment due
to breast cancer evaluated their satisfaction with life on a mediocre level.
Younger patients had a lower satisfaction with life than those who were older.
Women living in urban areas evaluated their satisfaction with life in more
positive terms than rural women. In turn, education level, marital status and
material standard had no effect on the level of satisfaction with life among the
women in the study. CONCLUSIONS: According to the SWLS, women with the diagnosis
of breast cancer obtained a mean result of 5.64 sten scores Younger women
evaluated their satisfaction with life in more positive terms than those who were
older. Women who lived in urban areas obtained a considerably higher result
according to the SWLS, compared to rural inhabitants. Marital status, education
level, material standard and occupational activity of the women were
insignificant in the respondents' evaluation of satisfaction with life.
PMID- 29936806
TI - Impacts of long-term ragweed pollen load and other potential risk factors on
ragweed pollen allergy among schoolchildren in Hungary.
AB - INTRODUCTION AND OBJECTIVE: Hungary is one of the areas in Europe most infected
with ragweed (Ambrosia artemisiifolia L.) and its pollen, and is the most
important cause of seasonal allergic rhinoconjunctivitis in the country. The aim
of the study was to investigate the association between ragweed pollen allergy
and long-term ragweed pollen load, as well as analysis of the the impacts of
additional potential risk factors on health outcomes. MATERIAL AND METHODS: A
modified version of standardized questionnaires, based on the International Study
of Asthma and Allergy in Childhood, were completed by the parents of
schoolchildren aged 8 - 9 attending 3rd grade classes throughout the country.
Pollen load was calculated for each settlement from daily ragweed pollen
concentrations monitored by 19 monitoring stations in the country. Descriptive
and analytical statistical methods were applied. RESULTS: At national level there
was a significant inverse association between prevalence of ragweed allergy and
its pollen load, but significance was lost after excluding data from Budapest,
the capital city, due to the impact of urbanization. In the adjusted model,
parental atopic disease was the strongest risk factor (either parent had atopic
disease aOR=2.60; 95% CI=2.31-2.93 or both parents had atopic disease aOR=4.56;
95% CI=3.71-5.60). Further significant risk factors were male gender (aOR=1.52;
95% CI=1.36-1.71), lower respiratory infection in the first two years of life
(aOR=1.91; 95% CI=1.70-2.16), and unshared children's room (aOR=1.22; 95% CI=1.09
1.37). Allergy was significantly less common among children whose parents
received social aid (aOR=0.83; 95% CI=0.72-0.97) and whose mother smoked during
pregnancy (aOR=0.80; 95% CI=0.64-0.99). CONCLUSIONS: Higher ragweed pollen
exposure was not found to be associated with higher risk of ragweed allergy.
PMID- 29936807
TI - Satisfaction with interpersonal relations among employees of State Forests in
Poland.
AB - INTRODUCTION AND OBJECTIVE: The aim of this study is to assess the interpersonal
relations of employees of State Forests in Poland, as well as to indicate the
factors related to the level of satisfaction with the relations among people
employed in similar positions, and relations with superiors. MATERIAL AND
METHODS: The issues investigated were developed based on research conducted
between 2014-2015 among employees of State Forests in Poland. In each of the 9
forest districts selected, 25 people were selected for testing from 3 groups of
employees: foresters, deputy foresters and supervisors, together with
administrative staff. Altogether, 399 people took part in the study conducted by
means of a questionnaire. RESULTS: The study showed that the overall level of
satisfaction with interpersonal relations among employees of State Forests in
Poland is high. Analysis indicated that the demographic characteristics of
respondents, such as age, gender or place of residence, had no significant
influence on satisfaction with interpersonal relations in the workplace. However,
the level of satisfaction with interpersonal relations was positively affected by
a high level of overall job satisfaction and satisfaction with remuneration.
Decrease in the level of satisfaction was influenced by the accumulation of
stressful life events and employment in administration. CONCLUSIONS: Satisfaction
with interpersonal relationships in the workplace is an important indicator of
employee mental health. Studies have shown the need to broaden the scope of
research into the variables that determine the character and personality of an
employee.
PMID- 29936808
TI - Differences in myoelectric manifestations of fatigue during isometric muscle
actions.
AB - INTRODUCTION: Muscle fatigue has been studied for a long time with the use of a
wide variety of exercise models, protocols and assessment methods, among which
surface electromyography (sEMG) is most commonly used. The main sEMG parameters
(amplitude and frequency) are prevalently used to evaluate the level of muscle
fatigue in static and dynamic contractions. OBJECTIVE: The purpose of this study
is to determine and compare 2 separate indices: IF1 basis of the sEMG
signal amplitude analysis and IF2 basis of the sEMG median frequency
analysis, related to muscles fatigue during an isometric contraction. MATERIAL
AND METHODS: The study was performed on 60 professional runners divided into 2
equal groups. The first group comprised sprinters, competing in short distance
track and field events (100 and 200 meters). The second group consisted of middle
distance runners, competing in middle-distance track and field events (800 and
1,500 meters). The electrical activity of the VMO muscles of the right and left
lower limbs was recorded simultaneously during isometric activity in a squatting
position. The sEMG data was used to determine and compare IF1 and
IF2 indices. RESULTS: During isometric measurement, sprinters
presented a much more significant increase in the mean amplitude of sEMG signal
in comparison to middle-distance runners (mean IF1 difference: 0.228;
p=0.007). Analysis of the median frequency did not show significant differences
between the 2 groups (mean IF2 difference: 0.037; p=0.12).
CONCLUSIONS: Change in sEMG amplitude during isometric exercise may be related to
muscles fatigue. The use of fatigue indices, based on sEMG amplitude, as an
objective indicator of the efficacy of an endurance training programme for
sportsmen requires further research.
PMID- 29936809
TI - Biomonitoring the indoor environment of agricultural buildings.
AB - INTRODUCTION: Agricultural hygiene and biomonitoring helps protect people,
livestock and crops from pests and disease, including insects, parasites,
pathogens and weeds. Optimising the health of animals and crops increases
productivity, minimises animal suffering, and ultimately protects human health by
ensuring that foodstuffs are safe for consumption. A healthy farm environment
also protects the health of the agricultural workers. Ensuring hygiene and health
protection is one of the basic construction requirements. Such requirements are
examined when commissioning new constructions and examining defects in
constructions already in use. One substantial defect is biocorrosion which
represents a synergistic process with a complex variety of factors, caused by
biochemical manifestations of various micro-organisms micromycetes). Micromycetes
producing mycotoxins therefore play an important role regarding the so-called
'Sick Building Syndrome' (SBS) that has become a global problem nowadays.
Therefore, agricultural hygiene and biomonitoring aims to minimise the
introduction of additional pathogens and pests, as well as the spread of
pathogens and pests in farm environments; this helps protect the safety of
foodstuffs further down the supply chain. OBJECTIVE: The aim of the presented
study is to point out the need to address indoor environment monitoring,
summarizing the most commonly used methods for monitoring biological factors, and
characterizing the negative effects of biological agents on humans and animals
exposed to their negative effects.
PMID- 29936810
TI - Analysis of Fraxinus pollen seasons and forecast models based on meteorological
factors.
AB - INTRODUCTION AND OBJECTIVE: The timings of Fraxinus and Betula flowering and
pollen release overlap, which may cause increased allergic reactions in sensitive
people. The aim of the present study was to characterize Fraxinus pollen seasons
in Lublin (central-eastern Poland) and to identify meteorological factors that
most determine the occurrence of airborne pollen of this taxon, as well as obtain
forecast models for the basic characteristics of the pollen season. MATERIAL AND
METHODS: The study was conducted in Lublin during the period 2001-2016, employing
the volumetric method. The seasons were compared by PCA (Principal Component
Analysis). To determine relationships between meteorological conditions and the
pattern of pollen seasons, regression analysis was used. Data for the period 2001
2015 were used to create forecast models by applying regression analysis, while
the 2016 data served to verify these models. RESULTS: Season end date and
seasonal peak date were characterized by the lowest variation. The biggest
differences were found for peak value and total annual pollen sum. The average
dates of occurrence of ash pollen grains in the air of Lublin were between 13
April 13 - 3 May 3, whereas, on average, the pollen peak date occurred on 23
April. The factor loading values for the PC1 variable indicate that it is most
strongly correlated with peak value and total pollen sum, while the PC2 variable
correlated with the pollen season start date and season duration (a negative
correlation). Regression models were developed for the following pollen season
characteristics: season start, end and duration, seasonal peak date, and total
annual pollen sum. CONCLUSIONS: The fit of the forecast models was at the level
of 62-94%. Analysis of the data showed that weather conditions mainly in February
were important factors controlling the Fraxinus pollen season.
PMID- 29936811
TI - Activity of selected essential oils on spoiling fungi cultured from Marzolino
cheese.
AB - Microscopic fungi can be present on a variety of foodstuff, including cheese.
They can be responsible for fungal spoilage, causing sensory changes making food
unacceptable for human consumption, and posing severe health concerns.
Furthermore, some of these organisms are able to resist antimicrobial
preservatives provided for by law. Antifungal activity of 15 chemically defined
EOs, alone and in mixture, were checked by a microdilution test against isolates
of Penicillium funiculosum and Mucor racemosus cultured from rinds of Marzolino,
a typical Italian fresh pecorino cheese. Origanum vulgare yielded the lowest MIC
values, followed by Salvia sclarea, Ocimum basilicum and
Cymbopogon citratus, while Citrus paradisi and Citrus limon
were not active. All mixtures showed antifungal activity at lower concentration
with respect to MIC values of each EO component, when not in combination. This
study is the first to describe the setting up of EOs mixtures to limit spoiling
moulds.
PMID- 29936812
TI - Microbiological analysis of bioaerosols collected from Hospital Emergency
Departments and ambulances.
AB - INTRODUCTION AND OBJECTIVE: The goal of the study was a microbiological,
qualitative and quantitative analysis of bioaerosol at the workplace of medical
personnel (Health Emergency Departments (HEDs), ambulances), and comparative
administration offices with an expected neutral occupational exposure to
biological agents measured with individual Button Sampler. MATERIAL AND METHODS:
Personal sampling was performed with Button Sampler instrument loaded with
gelatine filters in 10 HEDs, in 9 ambulances and in 9 offices to assess the
occupational biological agents' exposure in air. Sampling was conducted from
March until April 2016. Samples were quantitatively assessed for viable and total
number of bacteria and fungi. Routine procedures for microbiological diagnostics
were implemented. Data were analysed using Kruskal-Wallis and Mann-Whitney
statistical tests with alpha=0.05. P value less than 0.05 were considered
significant. RESULTS: At the workplaces assessed, the concentrations of viable
microorganisms in HEDs were 1.3*102 - 4.2*103
CFU/m3 for bacteria, 3.4*100 - 8.1*101
CFU/m3 for fungi; in ambulances 1.3*102 -
1.4*103 CFU/m3 (bacteria), 6.7*100 -
6.5*102 CFU/m3 (fungi) and in offices 4.2*101 -
5.0*103 CFU/m3 (bacteria), 0 - 7.9*102
CFU/m3(fungi). In outdoor air, the number of microorganisms reached
the level: 1.0*102 - 5.9*102 CFU/m3 for bacteria
and 1.5*102 - 8.2*102 CFU/m3 for fungi. The
predominant isolated bacteria were Gram-positive cocci. The prevalent fungi
species belonged to the genus Aspergillus and Penicillium.
CONCLUSIONS: The quantitative assessment of examined indoor air was similar to
control outdoor air, and were relatively low. The level of microbiological
contamination did not exceed 5*103 CFU/m3 which is
recommended as an admissible level in public spaces in Poland.
PMID- 29936813
TI - Extent of protective or allergy-inducing effects in cats and dogs.
AB - OBJECTIVE: The study aimed to assess the effect of fur-bearing pets, including
cats and dogs, on the health of individuals with allergic conditions. MATERIAL
AND METHODS: The study group comprised 18,617 individuals (16,562 from urban and
2,055 from rural areas). The tool used in the study was the European Community
Respiratory Health Survey (ECRHS) and International Study of Asthma and Allergies
in Childhood (ISAAC) study questionnaire, adapted to European conditions (Middle
and Eastern Europe) and used as part of the study Implementation of a System for
the Prevention and Early Detection of Allergic Diseases in Poland. RESULTS: The
factors determining the keeping of fur-bearing pets in a household included a
larger living space and the number of cigarettes smoked, which were observed
especially in urban settings. The keeping of fur-bearing animals in rural areas
acts preventively against allergic conditions, while in urban areas, these
animals were a factor clearly aggravating symptoms of bronchial asthma - the risk
of cough (OR 1.921; CI 10-3.36; P=0.02) and wheezing (OR 2.60; CI 1.22-5.54;
P=0.01). CONCLUSIONS: Fur-bearing animals kept in rural settings exhibit
preventive effects on the development of allergies; whereas in urban areas they
exacerbate allergic symptoms, especially the symptoms of bronchial asthma.
PMID- 29936814
TI - Occupational exposure level of pig facility workers to chemical and biological
pollutants.
AB - OBJECTIVE: The aim of the study was to assess the impact of a fattening season on
the level of airborne chemical and microbial pollutants in the pig fattening
house. MATERIAL AND METHODS: Evaluation of the air composition as well as the
microbiological air quality were made during 2 series, i.e. in the summer and
winter period of fattening. Airborne gaseous pollutants were analyzed by gas
(organic compounds) and liquid (inorganic compounds) chromatography methods. Air
microbial contamination was determined in compliance with the Polish Standard PN
EN 13098:2007. RESULTS: The air/gas composition in the pig unit showed that
irrespective of the fattening season, the level of determined pollutants -
especially ammonia, volatile organic compounds (VOCs), including methanethiol and
total dust - could have an adverse effect on the health of swine facility
workers. The investigated pig building was found to be a source of chemical
pollutants as well as biological agents. The total bacterial count in 1 m3 of air
was 3.6*106 and 4.6*106 cfu, during the winter and summer periods of fattening,
respectively. Gram-positive cocci predominated in both seasons. In the winter,
fungi of the Trichoderma genus were represented equally often. In the summer
period, up to 90% of the isolated fungus was Aspergillus spp. CONCLUSIONS:
Workers engaged in swine rearing and production are occupationally exposed not
only to a high concentration of microbial contamination, but also to irritating
and odorogenous volatile compounds. Thus, activities directed at the promotion of
health prevention strategies, as well as effective guidelines for safe and
hygienic animal housing, should be implemented.
PMID- 29936815
TI - Effect of ambient air temperature and solar radiation on changes in bacterial and
fungal aerosols concentration in the urban environment.
AB - Bioaerosols are particularly sensitive to sterilization processes due to their
biological characteristics. Phenomena occurring in the atmosphere have major
influence on airborne bacteria and fungi concentration levels. The presented
study evaluates the sterilization properties of ambient air temperature and solar
radiation on viable bioaerosols concentration levels in outdoor air in Gliwice,
Poland. Assigned were the breakpoints indicating limited stimulation properties
of the air temperature, which amounted 7.5 degrees C for bacterial aerosol and
16.5 degrees C for fungal aerosol. Also revealed was the influence of solar
radiation properties on decreasing the bioaerosols concentration levels. Both
bacterial and fungal viable aerosol were sensitive to this radiation, although
the phenomenon was more effective for airborne bacteria.
PMID- 29936816
TI - Occupational risks related to vibrations using a brush cutter for green area
management.
AB - INTRODUCTION: Weed control is one of the most important issues in the maintenance
sectors of both agriculture and green areas. Small tools are employed for
controlling grass and other growths on steep verges and river banks. This leads
the operators being exposed to many risks among which vibration is one. The
purpose of this study is to measure and evaluate hand-arm vibration and to verify
the daily exposure to which workers are often subjected while weeding. MATERIAL
AND METHODS: Two cutting heads, a brush knife and a mowing head were compared.
Both were mounted on the same cow-horn brush cutter. The vibration total value
was expressed as the root-mean-square (rms) of three component values according
to the axes X, Y and Z. The signal was frequency weighted using the weighting
curve Wh, as described in the ISO 5349-1 (2001) standard. In addition, the daily
vibration exposure was calculated and compared with the thresholds set by EU
Directive 2002/44/EC (2005). RESULTS: The obtained results showed that the
exposure action value (EAV) of 2.5 ms-2 was exceeded while using both cutting
heads. The exposure limit value (ELV) using the brush knife also exceeded 5 ms-2.
CONCLUSIONS: The results highlighted important aspects in terms of exposure
values that should be considered with the view of preventing the risk of Hand-Arm
Vibration Syndrome (HAVS) to which the operators who frequently use these tools
are exposed. Specific measures should therefore be taken to protect the exposed
workers.
PMID- 29936817
TI - Hepatitis E - A new era in understanding.
AB - Hepatitis E virus [HEV], the last of the five hepatotropic viruses to be
discovered, was originally considered to cause an acute, travel-associated self
limiting illness restricted to humans; however, new research shows that there are
animal reservoirs and zoonotic transmission. Additionally, HEV is now considered
as a major health burden worldwide, leading to significant morbidity and
mortality; therefore, the topic of hepatitis E is of re-emerging importance,
having brought to light important questions such as the transmission of HEV,
especially in developed countries, as well as treatment and vaccination options.
HEV belongs to the genus Hepevirus in the Hepeviridae family. The HEV
genome sequence is relatively stable; however, there is a diversity of genotypes
which are helpful in comprehending the epidemiological phenomena. HEV is
classified based on the nucleotide sequences of the genome and is now
characterised as a single serotype with four major genotypes [HEV 1-4]. Hepatitis
E cases are not clinically distinguishable from other types of acute viral
hepatitis, although diagnosis can be strongly suspected in certain
epidemiological settings. It is imperative to raise awareness among physicians
about the importance of HEV, with the aim of helping recognise, prevent and treat
HEV infections. This review article highlights the current developments of HEV in
microbiology, epidemiology, clinical features, treatment and prophylaxis.
PMID- 29936818
TI - Neurological and mental health outcomes among conventional and organic farmers in
Indiana, USA.
AB - INTRODUCTION: Every farming method, whether conventional or organic, has been
associated with some sort of risky behaviors leading to health issues among
farmers. Substantial evidence is not available in the literature to determine
whether the magnitudes of health outcomes vary between conventional and organic
farmers. The study investigated whether self-reported neurological and mental
health symptoms differ between conventional and organic farmers living in
Indiana, USA. MATERIAL AND METHODS: A self-reported questionnaire survey
collected information from 200 conventional and 157 organic farmers of Indiana on
demographic characteristics, depression and neurological symptoms. Statistical
analyses were conducted to observe the differences in self-reported symptoms by
groups of farmers. RESULTS: It was observed that the conventional farmers had
significantly higher age-adjusted mean neurological symptom score (p<0.01) than
the organic farmers. Regression models revealed positive and significant
associations of conventional farming with total (beta =1.34; p=0.02), sensory
(beta =0.83; p=0.001) and behavioural (beta =0.09; p=0.03) symptoms after
accounting for age, income, education and years in farming. Positive but non
significant associations were also observed in conventional farmers with
cognitive and motor symptoms, and with all subscales of depression symptoms in
the adjusted models. CONCLUSIONS: The findings obtained suggest the importance of
a larger study to further explain the difference in mental and neurological
health effects in these two categories of farmers.
PMID- 29936819
TI - Physical medicine after limb transplantation. Therapeutic effects of physical
procedures in the treatment of limb transplantation after cut-off by a threshing
machine - Case report.
AB - INTRODUCTION: Introduction. The number of accidents in agriculture involving
children as the victims continues to increase year-by-year. Parents often allow
children to perform certain tasks, or even entrust them to perform such tasks as
a duty. CASE REPORT: The paper presents results of treatment using a 3D magnetic
field in a 31-year- old patient after transplantation of the upper extremity of
the arm. Amputation of the extremity had been caused by an accident (hand cut-off
by a threshing machine). The therapeutic cycle for the patient constituted of 3
series of 15 daily procedures, performed for 15 minutes. There was a break of 4
weeks between sessions. Additionally, the patient performed kinesitherapy
exercises in the outpatient clinic. CONCLUSIONS: The results obtained regarding
improvement of the functional condition of the limb showed that in the complex
planning of treatment, the taking into account of the physical medicine
procedures should be indispensable.
PMID- 29936820
TI - Skin lesions in humans bitten by European pigeon tick Argas reflexus
(Fab.) (Ixodida: Argasidae) massively occurring in the Upper Silesian conurbation
of south-west Poland.
AB - INTRODUCTION AND OBJECTIVE: The great number of pigeon populations in many
European cities promotes the spread of the European pigeon tick (Argas
reflexus), the bites of which cause local and systemic reactions. The aim was
to study the occurrence of A. reflexus in several cities of Upper Silesia,
and skin lesions caused by A. reflexus tick bites in humans. MATERIAL AND
METHODS: The results of investigations carried out in 1995-2002 in five cities
located in the Upper Silesian conurbation are presented. Specimens of A.
reflexus were collected for one hour in attics and lofts inhabited by these
ticks. A history of skin lesions caused by bites was taken from residents who had
been infested by A. reflexus. The development of skin lesions was
monitored for three months in two individuals who had been bitten several times
by these arthropods. RESULTS: In the localities, 987 A. reflexus specimens
were collected, including 334 females, 269 males, and 384 various nymphal stages.
Within one hour, 38-109 ticks specimens were collected at the study sites. Cases
of attacks by unengorged A. reflexus were reported in all the habitats
located in the residential buildings; the ticks were also found in residents'
flats and in staircases. Residents who had been repeatedly attacked by European
pigeon ticks developed a strong inflammatory reaction to the components of tick
saliva, and had purple papules with necrosis in the centre of the lesion. The
tick bite areas exhibited scars and hyperpigmentation. CONCLUSIONS: Individuals
attacked by A. reflexus several times are at risk of development of severe
persistent local reactions to bites. Pigeon ticks, trophically associated with
pigeons present abundantly in the Upper Silesian conurbation and other European
urban habitats, pose a serious threat to public health.
PMID- 29936821
TI - Thrombocytopenia resistent to standard therapy in lupus patients - analysis of 3
cases and clinical statement.
AB - Hematologic disorders, including thrombocytopenia, are a common symptom of
systemic lupus - Systemic Lupus Erythematosus (SLE). An important diagnostic and
therapeutic issue is the severe and recurrent thrombocytopenia resistant to
standard treatment. It requires extensive diagnostics and a multi-directional
view on its causes beyond the autoimmune process. Currently, there is no single
treatment regimen for these disorders. Corticosteroids (CS) are the first-line
drugs, but their chronic use is a big problem, they are not always successful and
often generate a number of complications, especially in moderate to high doses.
In the case of thrombocytopenia associated with the activity of SLE,
immunosuppressive therapy is the gold standard and may result in long-term
remission of symptoms and clinical stabilization. The major problem is
thrombocytopenia resulting from other causes, such as infection or medications.
This study discusses severe recurrent thrombocytopenia on the basis of three
clinical cases, analyzing both the various causes of disorders, and providing
ways of management and treatment. Special attention is paid to the correlation of
thrombocytopenia with the clinical and immunological activity of SLE. It seems
that severe and refractory thrombocytopenia may be a critical point and largely
determine the management and treatment possibilities of SLE.
PMID- 29936822
TI - Viral hepatitis C in Poland in the Silesian Province between 2005-2014.
AB - INTRODUCTION AND OBJECTIVE: Viral hepatitis C remains one of the major health and
social problems related to infectious diseases in Poland. The aim of the study
was assessment of the registered changes in the incidence of HCV in the Silesian
Province of western Poland during the last 10 years, including age, gender and
place of residence. MATERIAL AND METHODS: A retrospective analysis was performed
of the HCV incidence between 2005-2014 in the Silesian Province. The crude and
standardized incidence rates were calculated for males and females in each year.
Subsequently, the territorial diversity of the epidemiological situation in the
districts was assessed by calculating the average incidence rate over the entire
study period. RESULTS: Incidence rates calculated according to the case
definition of 2005 ranged between 5.95/100000 in 2005 to 10.36/100000 in 2014.
Analysis of the structure of the incidence showed that during the analyzed
period, the majority of hepatitis C cases were related to males (52.5%) rather
than females (47.5%), and hepatitis C was more prevalent in younger males (aged
20-49) and older females (aged over 50). After excluding the effect of age, the
standardized rates were twice as low, compared to the crude incidence rates.
CONCLUSIONS: An increase in the HCV incidence rate was observed in males and
females. It is obvious that the detection of additional cases will entail the
need to provide funding for the treatment of more patients, which should be
included in the map of regional health needs in the coming years. Our study
demonstrates the temporal and spatial variability of HCV incidence in the
Silesian Province of Poland. The observed increase in the crude and standardized
rates suggests that the current registry system of HCV in Poland is more
effective now. The current situation is comparable with the data in other EU
countries.
PMID- 29936823
TI - Influence of Pb and Cd levels in whole blood of postmenopausal women on the
incidence of anxiety and depressive symptoms.
AB - INTRODUCTION: To-date, the influence of heavy metals such as Pb or Cd on mental
functioning, and especially on the occurrence of depressive and anxiety-related
disorders, has not been well understood. OBJECTIVES: 1) Assessment of Pb and Cd
levels in whole blood of postmenopausal women. 2) Assessment of the severity of
anxiety and depressive symptoms depending on Pb and Cd levels in whole blood of
postmenopausal women. MATERIAL AND METHODS: The survey-based study involved 198
healthy postmenopausal women from West Pomeranian province in Poland. It was
performed using the Primary Care Evaluation of Mental Disorders (PRIME-MD),
Beck's Depression Inventory (BDI), and the State-Trait Anxiety Inventory (STAI).
The second part of the study was based on biochemical analysis of the levels of
heavy metals (Pb, Cd). RESULTS: The mean level of Pb was 19.85 +/- 8.99 ug/l and
Cd 0.87+/-0.98 ug/l; these levels were within normal ranges. Analysis of the mean
levels of Pb and Cd in whole blood of postmenopausal women in relation to the
severity of depressive symptoms did not reveal statistically significant
differences. Correlation analysis demonstrated a statistically significant
(p<0.05) negative correlation (-0.22) between the level of Pb and the severity of
anxiety as a state. Correlations between the levels of Pb and Cd and the severity
of anxiety as a trait were not statistically significant. CONCLUSIONS: The mean
Pb and Cd levels in whole blood of healthy postmenopausal women did not exceed
acceptable limits. The study did not confirm a relationship between the levels of
selected heavy metals and the severity of anxiety and depressive symptoms in
healthy women. However, there was a relationship between the level of Pb and the
severity of anxiety as a state.
PMID- 29936824
TI - Evaluation of trace metals in follicular fluid in ICSI-treated patients.
AB - This study investigated the influence of cadmium (Cd), copper (Cu), iron (Fe),
lead (Pb), selenium (Se), and zinc (Zn) in follicular fluid on the effectiveness
of in vitro fertilization (IVF) treatment and the dynamics of embryo development.
The study involved 221 women aged 25-35 years in whom intracytoplasmic sperm
injection (ICSI) was performed. Analysis of the effects of the average
concentrations of Se, Zn, and Cu on the evelopmental dynamics of embryos showed
that higher concentrations of these metals were accompanied by shorter lead times
for each of the various stages of development, while the reverse was true in the
case of cadmium and lead. No relationship was observed between the mean
concentrations of Fe and the dynamics of the human embryo. In order to discover
whether the fact of becoming pregnant is affected by the investigated variables,
a logistic regression model was applied. The dependent variable was the fact of
achieving pregnancy, and the independent variable tested was the level of trace
metals. Ultimately, only one variable remained statistically significant in the
model: the level of Se.
PMID- 29936825
TI - Pulmonary actinomycosis - the great imitator.
AB - Pulmonary localisation represents only 15% of all cases of actinomycosis. The
clinical symptoms and radiological changes of this disease are non-specific and
sometimes it can be misdiagnosed, usually as tuberculosis, lung cancer or lung
abscess. In the reported case, what might look like the lung cancer, finally
turned out to be actinomycosis. The interesting case is presented of lung
actinomycosis in a 77-year-old farmer, admitted to the Department of
Pneumonology, Oncology and Allegology in Lublin due to a massive haemoptysis. CT
scan of the chest showed, apart from other changes, the spicular consolidation in
the right lung which aroused oncology vigilance. The diagnostic path, which was a
real medical challenge, led to the diagnosis of actinomycosis. The process of
diagnosis and consequent treatment, which led to the complete regression of
clinical and radiological changes, is presented.
PMID- 29936826
TI - Utilisation of peptides against microbial infections - a review.
AB - The emergence of resistance in microorganisms on a global scale has made it
necessary to search for new antimicrobial factors. Antimicrobial peptides (AMPs)
seem to meet these expectations. AMPs are produced by bacteria, viruses, plants,
and animals, and may be considered as a new class of drugs intended for the
prophylaxis and treatment of both systemic and topical infections. The aim of
this study is to review the results of studies on the use of peptides to combat
infections in vivo. Antimicrobial peptides may be applied topically and
systemically. Among the peptides used topically, a very important area for their
application is ophthalmology. AMPs in ophthalmology may be used mainly for the
protection of contact lenses from ocular pathogens. Many AMPs are in clinical
trials for application in the therapy of local infections. There may be mentioned
such preparations as: pexiganan (magainin analogue), MX-226 (based on
indolicidin), NEUPREX (isolated from human BPI (bactericidal/permeability
increasing) protein), IB-367 (variant of porcine protegrin), P113 (based on
histatin), daptomycin, polymyxins, as well as peptidomimetics. In the combat
against systemic infections are used such peptides as: P113D (modified P113
peptide containing D-amino acids), colistin, peptoids, and peptides containing
non-typical amino acids or non-peptide elements. AMPs are also used as
antiprotozoal, antifungal, antitoxic and immunostimulatory agents. The
limitations in the use of peptides in the treatment of infections, such as
susceptibility to proteolysis, and resistance of microorganisms to the peptides,
are also discussed. AMPs are a promising strategy in the fight against microbial
infections.
PMID- 29936827
TI - Deciphering Protein O-Glycosylation: Solid-Phase Chemoenzymatic Cleavage and
Enrichment.
AB - Glycosylation plays a critical role in the biosynthetic-secretory pathway in the
endoplasmic reticulum (ER) and Golgi apparatus. Over 50% of mammalian cellular
proteins are typically glycosylated; this modification is involved in a wide
range of biological functions such as barrier formation against intestinal
microbes and serves as signaling molecules for selectins and galectins in the
innate immune system. N-linked glycosylation analysis has been greatly
facilitated owing to a range of specific enzymes available for their release.
However, system-wide analysis on O-linked glycosylation remains a challenge due
to the lack of equivalent enzymes and the inherent structural heterogeneity of O
glycans. Although O-glycosidase can catalyze the removal of core 1 and core 3 O
linked disaccharides from glycoproteins, analysis of other types of O-glycans
remains difficult, particularly when residing on glycopeptides. Here, we describe
a novel chemoenzymatic approach driven by a newly available O-protease and solid
phase platform. This method enables the assignment of O-glycosylated peptides, N
glycan profile, sialyl O-glycopeptides linkage, and mapping of heterogeneous O
glycosylation. For the first time, we can analyze intact O-glycopeptides
generated by O-protease and enriched using a solid-phase platform. We establish
the method on standard glycoproteins, confirming known O-glycosites with high
accuracy and confidence, and reveal up to 8-fold more glycosites than previously
reported with concomitant increased heterogeneity. This technique is further
applied for analysis of Zika virus recombinant glycoproteins, revealing their
dominant O-glycosites and setting a basis set of O-glycosylation tracts in these
important viral antigens. Our approach can serve as a benchmark for the
investigation of protein O-glycosylation in diseases and other biomedical
contexts. This method should become an indispensable tool for investigations
where O-glycosylation is central.
PMID- 29936828
TI - Tyrosine Sulfation Restricts the Conformational Ensemble of a Flexible Peptide,
Strengthening the Binding Affinity for an Antibody.
AB - Protein tyrosine sulfation (PTS) is a post-translational modification regulating
numerous biological events. PTS generally occurs at flexible regions of proteins,
enhancing intermolecular interactions between proteins. Because of the high
flexibility associated with the regions where PTS is generally encountered, an
atomic-level understanding has been difficult to achieve by X-ray crystallography
or nuclear magnetic resonance techniques. In this study, we focused on the
conformational behavior of a flexible sulfated peptide and its interaction with
an antibody. Molecular dynamics simulations and thermodynamic analysis indicated
that PTS reduced the main-chain fluctuations upon the appearance of sulfate
mediated intramolecular H-bonds. Collectively, our data suggested that one of the
mechanisms by which PTS may enhance protein-protein interactions consists of the
limitation of conformational dynamics in the unbound state, thus reducing the
loss of entropy upon binding and boosting the affinity for its partner.
PMID- 29936829
TI - Reaction-Based Detection of Chemical Warfare Agent Mimics with Affinity Ionic
Liquids.
AB - We are demonstrating here the successful development of an ionic liquid device
based on affinity ionic liquids AIL 1-6 tailored for chemoselective detection of
gaseous chemical warfare agent (CWA) mimics on a quartz crystal microbalance
(QCM) as well as on disposable filter papers. In the QCM platform, the negligible
vapor pressure of ionic liquids ensures that AILs do not dry out on quartz chips
and are used free of leakage during the measurements. This lack of vapor pressure
makes these ionic liquid devices highly attractive for gas analysis. In the
present study, chemoselective CWA mimic vapor detection by QCM occurs when gas
rapidly diffuses into the AIL thin film and accordingly the nucleophilic
substitution reaction emerges under the experimental conditions developed. Our
initial results give credence to three important conclusions: (i) AILs could be
prepared in short synthetic steps and are remarkable in detecting CWA mimics,
(ii) the analysis of gaseous CWA mimics on QCM is label-free and chemoselective,
and (iii) the detection of CWA mimic vapor by AILs on filter paper discs is
colorimetric and portable, and, once used, the paper disc can be disposed. To the
best of our knowledge, this is the first report in the literature based on the
CWA mimic vapor detection in ionic liquids on a QCM.
PMID- 29936830
TI - Multiparametric Sensing of Membrane Bilayer Properties with a Highly Environment
Susceptible Fluorophore.
AB - Push-pull type fluorophores are often exploited as a biological probe because of
their high environment-sensitivity nature. Herein, we report the potentiality of
a push-pull fluorophore, 2-formyl-5-(4'- N, N-dimethylaminophenyl)thiophene, as a
membrane probe. This molecule exhibits strong absorbance in the violet region
(~400 nm) and a high emission quantum yield (<=0.6). The emission is highly
sensitive to the surrounding environment, and a high Stokes shift (>7000 cm-1)
appears in strong polar solvents. The molecule is highly susceptible to the
fluorescence quenching by protic solvents. The neutral probe efficiently senses
aprotic environments such as lipid bilayer membranes through all six fluorescence
parameters: emission maxima, intensity, and anisotropy as well as the
corresponding time-dependent parameters. The small and flat shape, nonemissive
nature in the aqueous medium along with the high susceptibility to all six
fluorescence parameters of the molecule strongly suggests a promising
fluorescence probe for biological medium.
PMID- 29936831
TI - Dramatic Enhancement of Quantum Cutting in Lanthanide-Doped Nanocrystals
Photosensitized with an Aggregation-Induced Enhanced Emission Dye.
AB - Applications of multiphoton processes in lanthanide-doped nanophosphors (NPs) are
often limited by relatively weak and narrow absorbance. Here, the concept of an
ultimate photosensitization by aggregation-induced enhanced emission (AIEE) dyes
to overcome this limitation is introduced. Because AIEE dyes do not suffer from
concentration quenching, they can fully cover the NP surface at high density to
maximize absorbance while passivating the surface. This concept is applied to
multiphoton down-conversion by quantum cutting. Specifically, coating Yb3+/Tb3+
doped NPs with an AIEE dye designed for efficient energy transfer and attachment
to the NPs produces a 2260-fold enhancement of multiphoton down-conversion by
quantum cutting with remarkable photostability. In a prototypical application,
the quantum cutting of UV photons to near-infrared photons that are matched to
the band gap of a silicon solar cell produces an average 4% increase in
efficiency under concentrated solar illumination. This provides a general
strategy for NP photosensitization that can be applied to both multiphoton up-
and down-conversion.
PMID- 29936832
TI - Total Synthesis of Isodihydrokoumine, (19 Z)-Taberpsychine, and (4 R)
Isodihydroukoumine N4-Oxide.
AB - We report the total synthesis of the natural products isodihydrokoumine and (19
Z)-taberpsychine in 11 steps each and (4 R)-isodihydrokoumine N4-oxide in 12
steps from commercially available starting materials. The key reactions include
an intramolecular [3 + 2] nitrone cycloaddition and Lewis acid mediated
cyclizations of a common intermediate to provide the core structures of either
taberpsychine or isodihydrokoumine.
PMID- 29936834
TI - Identification of the Histidine Residue in Vitamin D Receptor That Covalently
Binds to Electrophilic Ligands.
AB - We designed and synthesized vitamin D analogues with an electrophile as covalent
modifiers for the vitamin D receptor (VDR). Novel vitamin D analogues 1-4 have an
electrophilic enone group at the side chain for conjugate addition to His301 or
His393 in the VDR. All compounds showed specific VDR-binding potency and
agonistic activity. Covalent bond formations of 1-4 with the ligand-binding
domain (LBD) of VDR were evaluated by electrospray ionization mass spectrometry.
All compounds were shown to covalently bind to the VDR-LBD, and the abundance of
VDR-LBD corresponding conjugate adducts of 1-4 increased with incubation time.
Enone compounds 1 and 2 showed higher reactivity than the ene-ynone 3 and dienone
4 compounds. Furthermore, we successfully obtained cocrystals of VDR-LBD with
analogues 1-4. X-ray crystallographic analysis showed a covalent bond with His301
in VDR-LBD. We successfully synthesized vitamin D analogues that form a covalent
bond with VDR-LBD.
PMID- 29936833
TI - Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of
Site-Specific Quantitative O-GlcNAcomics.
AB - The dynamic posttranslational modification O-linked beta- N-acetylglucosamine
glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins
in the brain. Like phosphorylation, O-GlcNAcylation is inducible and plays
important functional roles in both physiology and disease. Recent advances in
mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of
O-GlcNAcylation events to individual sites in proteins. However, our
understanding of which glycosylation events are necessary for regulating protein
function and controlling specific processes, phenotypes, or diseases remains in
its infancy. Given the sheer number of O-GlcNAc sites, methods for identifying
promising sites and prioritizing them for time- and resource-intensive functional
studies are greatly needed. Revealing sites that are dynamically altered by
different stimuli or disease states will likely go a long way in this regard.
Here, we describe advanced methods for identifying O-GlcNAc sites on individual
proteins and across the proteome and for determining their stoichiometry in vivo.
We also highlight emerging technologies for quantitative, site-specific MS-based
O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O
GlcNAcylation dynamics at individual sites. These cutting-edge technologies are
beginning to bridge the gap between the high-throughput cataloguing of O
GlcNAcylated proteins and the relatively low-throughput study of individual
proteins. By uncovering the O-GlcNAcylation events that change in specific
physiological and disease contexts, these new approaches are providing key
insights into the regulatory functions of O-GlcNAc in the brain, including their
roles in neuroprotection, neuronal signaling, learning and memory, and
neurodegenerative diseases.
PMID- 29936835
TI - Gold Nanoparticle Layers on Polystyrene Microspheres of Controlled Structure and
Electrokinetic Properties.
AB - Formation of positively charged gold nanoparticle layers on polystyrene
microparticles (PSMs600) was studied using the electrokinetic and the
concentration depletion methods based on atomic force microscopy (AFM) and
scanning electron microscopy (SEM) imaging. Primarily, the dependence of
electrophoretic mobility of microparticles on the gold nanoparticle concentration
in the suspension was measured. These results were quantitatively interpreted in
terms of the three-dimensional electrokinetic model. This allowed to derive a
formula for calculating the coverage of nanoparticles under in situ conditions
whose validity was confirmed by direct SEM imaging of deposited gold
nanoparticles (AuNPs). Additionally, the maximum coverage of gold nanoparticles
for various ionic strengths was determined using a concentration depletion method
based on AFM imaging of residual particles deposited on the silica substrate. The
maximum coverage increased with ionic strength attaining a value of 0.35 for the
ionic strength of 3 * 10-3 M. This effect was attributed to the decreasing range
of lateral electrostatic interactions among deposited particles. The
electrokinetic properties of the gold nanoparticle layers were also evaluated in
pH cycling experiments that confirmed their stability. Beyond significance to
basic science, the new data acquired in this work confirm the feasibility of
preparing gold nanoparticle layers on polymer microparticles characterized by a
controlled structure, coverage, and electrokinetic properties.
PMID- 29936836
TI - Conformational and Organizational Insights into Serum Proteins during Competitive
Adsorption on Self-Assembled Monolayers.
AB - Physicochemical interactions of proteins with surfaces mediate the interactions
between the implant and the biological system. Surface chemistry of the implant
is crucial as it regulates the events at the interface. The objective of this
study was to explore the performance of modified surfaces for such interactions
relevant to various biomedical applications. Because of a wide range of surface
wettability, we aimed to study protein behavior (i.e., conformational changes and
their packing) during competitive protein adsorption. Three serum proteins
(bovine serum albumin, BSA; fibrinogen, FB; and immunoglobulin G, IgG) were
tested for their conformational changes and orientation upon adsorption on
hydrophilic (COOH and amine), moderately hydrophobic (mixed and hybrid), and
hydrophobic (octyl) surfaces generated via silanization. Modified surfaces were
characterized using Fourier-transform infrared spectroscopy, contact angle, and
atomic force microscopy (AFM) techniques. Adsorbed masses of proteins from single
and binary protein solutions on different surfaces were quantified along with
their secondary structure analyses. Maximum adsorbed protein masses were found to
be on negatively charged and hydrophobic (octyl) surfaces because of ionic and
hydrophobic interactions between protein molecules and surfaces, respectively.
Side-on and end-on orientations of adsorbed protein molecules were analyzed using
theoretical and AFM analyses. We observed compact and elongated forms of BSA
molecules on hydrophilic and hydrophobic surfaces, respectively. We further found
a linear increase in the alpha-helix content of BSA and beta-sheet contents of FB
and IgG proteins with the increasing side-on (%)-oriented protein molecules on
the surfaces. This indicates that side-on orientations of adsorbed FB and IgG
lead to the formation of beta-sheets. Sodium dodecyl sulfate polyacrylamide gel
electrophoresis was employed to quantify the protein types and their ratio in
competitively adsorbed proteins on different surfaces. A theoretical analysis was
also used to determine the % secondary structures of competitively adsorbed
proteins from BSA/FB and BSA/IgG solutions, which very well agreed with
experimental results. The competitive protein adsorption from both BSA/FB and
BSA/IgG solutions was found to be entropy-driven, as revealed by thermodynamic
studies performed using isothermal titration calorimetry.
PMID- 29936837
TI - Ab Initio Molecular Dynamics Reveal Spectroscopic Siblings and Ion Pairing as New
Challenges for Elucidating Prenucleation Aluminum Speciation.
AB - The characterization of prenucleation species is essential to understand
crystallization mechanisms across many chemical systems and often involves the
use of vibrational spectroscopy. Nowhere is this more evident than in the
development of "green" aluminum processing technologies, where detailed
understanding of the speciation of aluminum and its polynuclear analogues in
highly alkaline, low water solutions is elusive. The aluminate anion Al(OH)4-
predominates in alkaline conditions, yet equilibrium with dimeric species, either
MU-oxo Al2O(OH)62- or di-MU-hydroxo Al2(OH)82-, can be assumed. Using ab initio
molecular dynamics with full solvation and the presence of counterions, this work
reconciles previous contradictory studies that had concluded only a single
species under relevant solution conditions. We reveal that the two dimers are
energetically separated by 2 kcal/mol in pure water but that the stability of
each can be reversed by ion pairing expected in saturated salt solutions.
Simulated Raman and IR spectra for each species (accounting for anharmonicity and
the fluctuating solvating environment) provide the first proof that the
considered species are "spectroscopic siblings", whose multiple overlapping bands
prevent definitive assertions in terms of speciation when compared to the
experimental spectra. These observations are likely to hold in higher order
aluminate oligomers and as such present a massive challenge toward understanding
the crystallization mechanisms relevant to aluminum processing.
PMID- 29936838
TI - Assessing the Impact of Point Defects on Molecular Diffusion in ZIF-8 Using
Molecular Simulations.
AB - Because defects are ubiquitous in materials, they may play an important role in
affecting the performance of materials in practical applications. Here, we
investigate the influence of point defects on the diffusion of molecules
including water, hydrocarbons, and acid gases in zeolitic imidazolate framework-8
(ZIF-8) using molecular simulations. To make these simulations possible, we
introduce a force field that extends previous descriptions of pristine ZIF-8 to
include experimentally relevant point defects. In general, the point defects we
examined increase the local hopping rate for molecular diffusion, suggesting that
low concentrations of these defects will not dominate long-range molecular
diffusion in ZIF-8.
PMID- 29936840
TI - Synthesis of 1,4-Thiazepines.
AB - An efficient, general, and unprecedented methodology for the synthesis of 2
methylene-2,3-dihydro-1,4-thiazepines from N-propargylic beta-enaminones is
described. Initially, N-propargylic beta-enaminones were thionated with
Lawesson's reagent in good to high yields, and then the resulting N-propargylic
beta-enaminothiones were subjected to electrophilic cyclization. When treated
with zinc chloride in refluxing chloroform, N-propargylic beta-enaminothiones
underwent electrophilic cyclization to yield 2-methylene-2,3-dihydro-1,4
thiazepines in good to high yields. A general trend was observed for all N
propargylic beta-enaminothiones, and the cyclization proceeded with high
efficiency and large functional group tolerance. This process is also applicable
to the cyclization of internal alkyne-tethered N-propargylic beta-enaminothiones.
This operationally simple and facile method may represent a very rapid entry to a
library of functionalized 1,4-thiazepines in the area of pharmaceuticals.
PMID- 29936839
TI - Highly Regio- and Stereoselective Catalytic Synthesis of Conjugated Dienes and
Polyenes.
AB - Conjugated dienes and polyenes are typically synthesized by sequential
introduction of C?C bonds. Here, we report a practical and scalable, catalytic
dienylation that is highly regio- and stereoselective for both C?C bonds. The
reaction is enabled by a stereoselective palladium-catalyzed cross-coupling that
is preceded by a regioselective base-induced ring opening of readily available
sulfolenes. The dienylation reaction is particularly useful for the synthesis of
synthetically challenging dienes containing cis double bonds. We also show that
the reaction can serve as a synthetic platform for the construction of conjugated
polyenes.
PMID- 29936841
TI - Tailored-BODIPY/Amphiphilic Cyclodextrin Nanoassemblies with PDT Effectiveness.
AB - Amphiphilic cyclodextrins (aCDs) are an intriguing class of carrier systems
which, recently, have been proposed to deliver porphyrinoids and anticancer drugs
or combined dose of both for dual therapeutic applications. The design of
nanoassemblies based on aCD and photosensitizers (PSs) aims to preserve the
photodynamic therapy (PDT) efficacy of PS, reducing the tendency of PS to self
aggregate, without affecting the quantum yield of singlet oxygen (1O2)
production, and, not less importantly, minimizing dark toxicity and reducing
photosensitization effects. With this idea in mind, in this paper, we focus on
nanoassemblies between a non-ionic aCD (SC6OH) and halo-alkyl tailored iodinated
boron-dipyrromethenes (BODIPY) dye, a class of molecules which recently have been
successfully proposed as a stimulating alternative to porphyrinoids for their
high photodynamic efficacy. Nanoassemblies of BODIPY/aCD (BL01I@SC6OH) were
prepared in different aqueous media by evaporation of mixed organic film of aCD
and BODIPY, hydration, and sonication. The nanostructures were characterized,
measuring their hydrodynamic diameter and xi-potential and also evaluating their
time-stability in biological relevant media. Taking advantage of emissive
properties of the not-iodinated BODIPY analogue (BL01), nanoassemblies based on
aCD and BL01 were investigated as model system to get insight on entanglement of
BODIPY in the amphiphile in aqueous dispersion, pointing out that BODIPY is well
entrapped in monomeric form (tau ? 6.5 ns) within the colloidal carriers. Also
morphology and fluorescence emission properties were elucidated after casting the
solution on glass. BL01@SC6OH is easily detectable in cytoplasm of HCT116 cell
lines, evidencing the remarkable intracellular penetration of this nanoassembly
similar to free BODIPY. On the same cell lines, the photodynamically active
assembly BL01I/aCD shows toxicity upon irradiation. Despite the fact that free
BL01I is more PDT active than its assembly, aCD can modulate the cell uptake of
BODIPY, pointing out the potential of this system for in vivo PDT application.
PMID- 29936842
TI - Hydrophobic Polyampholytes and Nonfreezing Cold Temperature Stimulate
Internalization of Au Nanoparticles to Zwitterionic Liposomes.
AB - Nanomedicine relies on the effective internalization of nanoparticles combined
with polymeric nanocarriers into living cells. Thus, exploration of
internalization is essential for improving the efficacy of nanoparticle-based
strategies in clinical practice. Here, we investigated the physicochemical
internalization of gold nanoparticles (AuNPs) conjugated with hydrophobic
polyampholytes into cell-sized liposomes at a low but nonfrozen temperature. The
hydrophobic polyampholytes localized in the disordered phase of the membrane, and
internalization of AuNPs was enhanced in the presence of hydrophobic
polyampholytes together with incubation at -3 degrees C as compared to 25
degrees C. These results contribute toward a mechanistic understanding for
developing a model nanomaterials-driven delivery system based on hydrophobic
polyampholytes and low temperature.
PMID- 29936843
TI - Electron Transfer in Spacer-Free DNA Duplexes Tethered to Gold via dA10 Tags.
AB - Electrical properties of DNA critically depend on the way DNA molecules are
integrated within the electronics, particularly on DNA-electrode immobilization
strategies. Here, we show that the rate of electron transport in DNA duplexes
spacer-free tethered to gold via the adenosine terminal region (a dA10 tag) is
enhanced compared to the hitherto reported DNA-metal electrode tethering
chemistries. The rate of DNA-mediated electron transfer (ET) between the
electrode and methylene blue intercalated into the dA10-tagged DNA duplex
approached 361 s-1 at a ca. half-monolayer DNA surface coverage GammaDNA (with a
linear regression limit of 670 s-1 at GammaDNA -> 0), being 2.7-fold enhanced
compared to phosphorothioated dA5* tethering (6-fold for the C6-alkanethiol
linker representing an additional ET barrier). X-ray photoelectron spectroscopy
evidenced dA10 binding to the Au surface via the purine N, whereas dA5*
predominantly coordinated to the surface via sulfur atoms of phosphothioates. The
latter apparently induces the DNA strand twist in the point of surface attachment
affecting the local DNA conformation and, as a result, decreasing the ET rates
through the duplex. Thus, a spacer-free DNA coupling to electrodes via dA10 tags
thus allows a perspective design of DNA electronic circuits and sensors with
advanced electronic properties and no implication from more expensive, synthetic
linkers.
PMID- 29936844
TI - Nondegenerate Chiral Phonons in Graphene/Hexagonal Boron Nitride Heterostructure
from First-Principles Calculations.
AB - Triggered by the recent successful observation of previously predicted phonon
chirality in the monolayer tungsten diselenide [ Science 2018 , 359 , 579 ], we
systematically study the chiral phonons in the classical heterostructure of
graphene/hexagonal boron nitride (G/ h-BN) by first-principles calculations. It
is found that the broken inversion symmetry and the interlayer interaction of G/
h-BN not only open the phononic gaps but also lift the degeneracy of left-handed
and right-handed chiral phonons at the first-Brillouin-zone corners (valleys). At
valleys, the hybridization makes chiral phonon modes solely contributed from one
individual layer. Moreover, we demonstrate that the vertical stress is effective
to tune the degenerated phononic gap while keeping the valley-phonon chirality of
G/ h-BN heterostructure, which is favorable for the Raman or ultrafast infrared
spectroscopy measurement. We also analyze the pseudoangular momentum of valley
phonon modes, which provide important references for the excitation and
measurement of the chiral phonons in the process of electronic intervalley
scattering. Collectively, our results on the chiral phonons in the G/ h-BN
heterostructure system could stimulate more experimental and theoretical studies
and promote the future applications on the phonon-chirality-based phononics.
PMID- 29936845
TI - Applications of Pyrene Fluorescence to the Characterization of Hydrophobically
Modified Starch Nanoparticles.
AB - Several aspects of pyrene fluorescence were applied to gain an insight into the
nature of the microdomains in hydrophobically modified starch nanoparticles (HM
SNPs), prepared by reacting SNPs with propionic and hexanoic anhydride to yield
C3- and C6-SNPs, respectively. The fluorescence experiments took advantage of the
inherent hydrophobicity of pyrene to bind onto the hydrophobic domains generated
by the HM-SNPs, and its specific response to the polarity of its environment, to
probe its accessibility to quenchers such as oxygen or nitromethane dissolved in
water. The equilibrium constant KB for the binding of pyrene onto HM-SNPs, the
ratio ( I1/ I3)o describing the relative hydrophobicity of the microenvironment
experienced by pyrene, its lifetime (tauSNP), and the rate constant of quenching
of pyrene bound to the HM-SNPs by water-soluble nitromethane ( kqSNP) were
determined as a function of the degree of substitution and weight fraction (wt %)
of the hydrophobic modifier. The C3- and C6-SNPs yielded similar parameters at
low levels of hydrophobic modification, indicating higher hydrophobicity of the
modified SNPs with increasing modification level. However, SNPs modified with
more than 5 wt % of hexanoyl pendants all displayed enhanced hydrophobicity for
the C6-SNPs relative to the C3-SNPs. This substantial enhancement is attributed
to the formation of larger hydrophobic microdomains by the hexanoyl pendants of
the C6-SNPs above the 5 wt % C6-modification threshold, which did not occur with
the C3-SNPs. Finally, the size of the SNPs did not appear to influence their
relative hydrophobicity. These experiments demonstrate how the fluorescence of
pyrene can be harnessed to provide information about the relative hydrophobicity
of HM-SNPs.
PMID- 29936846
TI - Folate Ligand Orientation Optimized during Cell Membrane Mimetic Micelle
Formation for Enhanced Tumor Cell Targeting.
AB - Nanocarriers with strong tumor cell targeting ability have been expected to
overcome limitations of cancer chemotherapy. Herein, cell membrane mimetic
micelles were prepared from a random copolymer (PMNCF) containing cell membrane
phosphorylcholine zwitterion, cholesterol, and tumor cell targeting folic acid
(FA) at the side chain ends. Surface orientation of the FA ligand was optimized
during PMNCF micelle preparation by controlling solvent solubility for FA. The
out-oriented ligands on the micelles were immobilized by the strongly associated
hydration layer around the closely packed phosphorylcholine zwitterions. The
doxorubicin (DOX) loaded PMNCF micelles were demonstrated to reduce normal cell
toxicity to less than 20%. More significantly, HeLa and MCF-7 tumor cell killing
efficacy of the optimized formulation was enhanced to 160% compared with that of
free DOX. The excellent performances of the drug loaded PMNCF micelles on both
tumor cell killing and normal cell toxicity reducing efficacies reveal great
potential for developing advanced drug delivery system.
PMID- 29936847
TI - Photoinduced Surface Zwitterionization for Antifouling of Porous Polymer
Substrates.
AB - Surface functionalization of polymeric porous substrates is one of the most
important requirements to enhance their applications in the biomedical field. In
this study, we achieved photoinduced surface modification using a highly
efficient reaction of hydrophilic polymers bearing phosphorylcholine groups.
Polymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) units and 2-(
N-ethylanilino)ethyl methacrylate units were synthesized with attention to the
polymer architectures. The surface modification of the porous polyethylene (PE)
substrates was carried out by the coating of the MPC polymers with a
photochemical radical generator, followed by photoirradiation for a few minutes.
Surface analysis by attenuated total reflectance Fourier transform IR
spectroscopy and X-ray photoelectron spectroscopy indicated that the MPC polymer
layer was generated on the PE surface. Cross-sectional confocal microscopy images
showed that the MPC polymers were coated on the polymer surface, even inside the
porous structure of the PE substrate. After modification, the porous PE
substrates showed a significant increase in hydrophilicity and the water
penetration rate through the pores. Furthermore, the amount of protein adsorbed
on the PE substrate was reduced significantly by the surface modification. These
functionalities were dependent on the MPC polymer architectures. Thus, we
concluded that the photoreactive polymer system developed furnished the porous
substrates with antifouling properties.
PMID- 29936848
TI - DNA Oligonucleotide-Functionalized Liposomes: Bioconjugate Chemistry,
Biointerfaces, and Applications.
AB - Interfacing DNA with liposomes has produced a diverse range of programmable soft
materials, devices, and drug delivery vehicles. By simply controlling liposomal
composition, bilayer fluidity, lipid domain formation, and surface charge can be
systematically varied. Recent development in DNA research has produced not only
sophisticated nanostructures but also new functions including ligand binding and
catalysis. For noncationic liposomes, a DNA is typically covalently linked to a
hydrophobic or lipid moiety that can be inserted into lipid membranes. In this
article, we discuss fundamental biointerfaces formed between DNA and noncationic
liposomes. The methods to prepare such conjugates and the interactions at the
membrane interfaces are also discussed. The effect of DNA lateral diffusion on
fluid bilayer membranes and the effect of membrane on DNA assembly are
emphasized. DNA hybridization can be programmed to promote fusion of lipid
membranes. Representative applications of this conjugate for drug delivery,
biosensor development, and directed assembly of materials are briefly described
toward the end. Some future research directions are also proposed to further
understand this biointerface.
PMID- 29936849
TI - Investing in the Future.
PMID- 29936850
TI - Gambling disorder and obsessive-compulsive personality disorder: A frequent but
understudied comorbidity.
AB - Background and aims Epidemiological data have suggested that the prevalence of co
occurring personality disorders is particularly high in people with gambling
disorder (GD). Among the personality disorders, obsessive-compulsive personality
disorder (OCPD) appears to be the most common problem. The objective of this
study was to investigate the clinical presentation of GD with and without co
occurring OCPD. Methods We studied 25 subjects with current GD and lifetime
diagnosis of OCPD. They were matched for age and gender with 25 individuals with
current GD but no lifetime diagnosis of any personality disorder. Results
Subjects with GD and OCPD demonstrated (a) lower severity of gambling symptoms,
(b) slower progression from recreational gambling to full-blown GD, (c) preferred
individual forms of betting, (d) identified more triggers to gambling (specially
the availability of money and stress); and (e) reported less negative impact on
relational problems due to GD. Conclusions Our research provides further insight
on GD co-occurring with OCPD, such as increasing social support and improvement
of coping skills, especially to deal with financial difficulties and stress. Our
findings may lead to more customized and effective therapeutic approaches to this
frequent comorbidity.
PMID- 29936851
TI - Conceptualizing gambling disorder with the process model of emotion regulation.
AB - Introduction Nowadays, gambling disorder (GD) is a worldwide health issue and
there is a growing need to both improve our understanding of this disorder and to
tailor specific interventions for its treatment. Moreover, theoretical models and
preliminary empirical results suggest that difficulty in regulating emotional
states might be involved in GD. However, literature describing clinical and
theoretical aspects of emotional dysregulation among pathological gamblers (PGs)
shows a lack of systematic description. Objectives We aimed to provide, within an
exhaustive theoretical framework of emotion regulation (ER) processing, empirical
evidence supporting a conceptual model of GD as an ER affliction. Methods We
commented on empirical evidence on the relationship between ER and GD in the
light of two main conceptual models of emotion (dys)regulation. Results The
results suggest there are actual deficits of ER processing among PGs, manifesting
themselves through different ways and in different steps of the ER timeline. In
addition, dysregulation of positive emotions may play a central role in GD. From
a clinical point of view, we pointed out that deficits in ER might be multiple in
nature and an assessment for GD should be accurate to identify the specific
components accounting for the development and maintenance of the disorder. It
should also orientate the clinician in selecting therapeutic objectives.
Conclusions The nature of emotional states that are difficult to regulate might
account for the GD severity and indicate the subtype of PGs the patient belongs
to. Treatment programs should be tailored on the specificity of PGs.
PMID- 29936852
TI - Association between cardiac autonomic nervous dysfunction and the severity of
coronary lesions in patients with stable coronary artery disease.
AB - Objective Autonomic dysfunction is recognized in patients with coronary artery
disease (CAD) and is related to worse cardiovascular outcome. This study aimed to
evaluate cardiac autonomic nervous function by heart rate recovery (HRR) and
heart rate variability (HRV), and demonstrate their relationship with the
severity of coronary lesions in patients with stable CAD (SCAD). Methods
Consecutive patients without CAD (controls, n = 65) and those with SCAD (n = 63)
were included in this study. Patients with SCAD were further divided into single-
or two-/three-vessel disease, as well as <70% or >=70% stenosis subgroups. The
association between HRR/HRV and coronary lesions was analysed. Results HRR and
HRV values were significantly lower in the SCAD group compared with the control
group. Multivariate logistic regression analysis showed that abnormal HRR and HRV
were risk factors of SCAD. Moreover, delayed HRR was a risk factor of the
severity of coronary lesions. Conclusions Our results show that autonomic
function is impaired in patients with SCAD and delayed HRR is closely related to
the severity of coronary lesions.
PMID- 29936853
TI - [Laudation to the midwives. Midwives and the puerperal fever].
AB - Originally published in the Hungarian Postgraduate Journal of Gynecology and
Obstetrics (2016; 18: 209-2013). Reprint with the contribution and permission of
the Professional Publishing Hungary Kft., Budapest. Orv Hetil. 2018; 159(26):
1079-1083.
PMID- 29936854
TI - ?
PMID- 29936855
TI - [Ignac Semmelweis and the Hungarian Medical Weekly Journal].
AB - Ignac Semmelweis did not publish his discovery in Vienna - i.e., that the
puerperal fever may be prevented by careful washing of the hand in chlorine
solution (asepsis) - for ten years. The Medical Weekly started its publications
edited by Lajos Markusovszky in Pest in 1857. Semmelweis as a professor of
theoretical and practical obstetrics at the University of Pest published a study
about puerperal fever in the first volume, and Hungarian physicians became
familiar with Semmelweis' opinion from this medical journal. Semmelweis was not
only an author of the Medical Weekly, but he also edited a supplement of the
Medical Weekly entitled Gynaecology and Paediatry. The Medical Weekly published
regular accounts of the work of the clinic written by lecturers of Semmelweis and
articles describing the most interesting cases of the clinic. Orv Hetil. 2018;
159(26): 1065-1070.
PMID- 29936856
TI - [Semmelweis - a contemplating human. Scientific historical lessons].
AB - In this article we examine why Semmelweis's seemingly simple, logical and
practical discovery was categorically dismissed by the majority of his
contemporaries, and why even many years after his death it was accepted with such
reservation. We invoke wherever possible Semmelweis's own words citing from the
series of articles appearing in the 'Orvosi Hetilap' [Hungarian Medical Weekly
Journal] published in 1858 in Hungary, and also from the German language summary
of the Journal published in 1860. We came to the conclusion that although
Semmelweis did everything in his power to show the causal relationship between
the development of puerperal fever (childbed fever) and some infectious substance
on the hands of examining doctors and medical students, this was not convincing
enough. The predominant theory at the time held that infection was caused by
miasma transmitted in the air and therefore stubbornly precluded any notion of
infectious matter physically transmitted on unclean hands. We also concluded that
the causal sequence observed by Semmelweis was missing an essential empirical
element: visual proof of the infectious agent he correctly postulated as
physically transmitted. Visually demonstrating the presence of the infectious
agent by means of a microscope would have made his case. This finally did occur
but only two years after Semmelweis's death. Had the renowned Hungarian
obstetrician realized the significance of taking advantage of the opportunity
afforded by David Gruby who was conducting experiments in the same town, a more
convincing argument could have been made for his theory. In the 1840s and 1850s,
David Gruby was experimenting with various microscopic techniques and their
application with success in Vienna before continuing his work in France. Gruby's
work, especially that of microscopic observations of tissues, received
international acceptance. Therefore, the involvement of Gruby and his work with
microscopes to support Semmelweis's observations would most probably have
forestalled much of the criticism and rejection his theory was initially awarded
(among which perhaps Virchow's rejection proved the most damaging). Had
Semmelweis utilized microscopic techniques, he would have been celebrated among
the first to discover bacterial pathogens, contributing to the development of the
currently predominant germ theory. Failure to utilize the microscope was the root
cause leading to the tragedy of Semmelweis's rejection by the medical
establishment of the time. Despite the increasing numbers of scientists utilizing
the microscope at the University of Pest, offered to corroborate his daims with
microscopic observations. Efforts have been made have since been to rehabilitate
him as the key figure who not only discovered the method of transmission of
infectious disease, but also implemented measures of prevention. Elevating him
among the ranks of the ten greatest doctors who ever lived is certainly
recognition due, but sadly denied to him in his lifetime. Orv Hetil. 2018;
159(26): 1055-1064.
PMID- 29936857
TI - [Ignac Semmelweis, the Hungarian icon of perinatology was born 200 years ago].
PMID- 29936858
TI - [Recollection of the great predecessor by a late successor leader].
AB - Between 1990 and 2007, being the eighth successor leader following Ignac
Semmelweis at the university department of obstetrics in Baross Street, what
interested me mainly were the following: the lucky coincidences needed for the
great discovery, the doctor's hopeless struggles, the circumstances of his death,
his five burials and fourfold exhumations, the Hungarianization of his name and
the deliberate or unintentional mistakes related to him. In the recollection, my
impressions and experiences related to the great predecessor will be reviewed.
Orv Hetil. 2018; 159(26): 1071-1078.
PMID- 29936859
TI - [The savior of mothers and newborns, whom we shall always be proud of: Ignac
Semmelweis (1818-1865). One who defeated the disease, yet could not convince the
people, Doctor of Medical Sciences and Surgery, Master of Obstetrics, Professor
of Theoretical and Practical Obstetrics at the Pest Royal Hungarian University of
Sciences].
AB - Semmelweis finally achieved results from his persistent research work. Those
being the scientific analysis of clinical statistical data and his animal
experiments, which recognized the dreadful disease of puerperal fever and its
prevention. "He not only discovered the real cause of puerperal fever but he also
created antiseptic prophylaxis, which he introduced in obstetrics and laid the
foundations of modern surgery (asepsis). The theory and practice of asepsis
stemmed from the discovery of the etiology of puerperal fever and therefore
originating from the genius idea of Semmelweis. The discoveries of bacteriology
by Lister, Pasteur and Koch only provided a scientific proof of the intuitive
statements of Semmelweis." Semmelweis was a pioneer of clinical etiological
research whose findings were aggressively disapproved by his colleagues due to
earlier medical misunderstandings. Semmelweis is given due respect by posterity
as a remuneration, to all the bitterness that he had suffered throughout his
life. Semmelweis is considered the savior of mothers and infants. The Hungarian
nation is very proud of him as he is one of our models whose oeuvre is
acknowledged not only in Hungary but throughout the world. The message of his
short, tragic yet effective life is eternal. The figure of Ignac Semmelweis is
depicted as a statue and is placed in Chicago among the statues of the most
innovative doctors and health care professionals of the world. The statue of
Semmelweis is next to the statues of Louis Pasteur and Wilhelm Conrad Rontgen.
"Semmelweis reflex" is a new expression which appeared and spread in English
speaking countries. The word does not relate to a medical phenomenon but
describes a social phenomenon when experts or the whole society automatically
rejects discoveries and new recognitions without examination or justification.
This phenomenon frequently occurs, even in our times. Orv Hetil. 2018; 159(26):
1041-1054.
PMID- 29936860
TI - [The Public Hospital Medical Society and Ignac Semmelweis].
PMID- 29936861
TI - Ranpirnase Reduces HIV-1 Infection and Associated Inflammatory Changes in a Human
Colorectal Explant Model.
AB - Ranpirnase (RNP) is a low molecular weight type III endoribonuclease, which
demonstrates broad antiviral and antitumor properties. We sought to characterize
the antiviral activity of RNP against HIV-1 and to determine whether RNP
modulates local inflammatory changes associated with HIV infection in the
colorectal explant model. Colorectal explants were incubated for 2 h with HIV
1BaL, in the presence of increasing concentrations of RNP (0-60 MUg/mL). After
washing, explants were cultured for 14 days, with supernatant collected at days
3, 7, 10, and 14. All samples were assayed for HIV-1 p24. Additionally, 30
soluble inflammatory biomarkers were assayed in the day 3 supernatant sample.
Other biopsies were stimulated with lipopolysaccharides (LPS) (10 MUg/mL) in the
presence of RNP and soluble biomarkers assayed at day 3. RNP inhibited productive
infection of the colorectal explants with HIV-1BaL and induced a dose-dependent
decrease in 15/30 biomarkers. Affected biomarkers included IP-10, MDC, MIP
1alpha, MIP-1beta, TARC, IL12-p40, IL-15, IL-17, IL-1alpha, IL-7, IFNgamma, IL12
p70, IL-1beta, IL-4, IL-5, and TNF-beta. Similarly, RNP dose-dependent inhibition
was demonstrated in 7/30 biomarkers after LPS stimulation, all of which
overlapped with HIV-1BaL-induced biomarker changes. The ability of RNP to inhibit
both colorectal explant HIV-1BaL infection and inflammatory changes associated
with HIV-1 infection makes RPN a promising agent for topical rectal pre-exposure
prophylaxis.
PMID- 29936862
TI - Implementation and Impact of a Hospital-Wide Instrument Set Review: Early
Experiences at a Multisite Tertiary Care Academic Institution.
AB - A multidisciplinary team of nurses, sterile processing technicians, and surgeons
reviewed 609 otolaryngology-head and neck surgery (OHNS) surgical instrument sets
at the study institution's 3 hospitals. Implementation of the 4-phase instrument
review resulted in decreased OHNS surgical instrument set types from 261 to 234
sets, and a decreased number of instruments in these sets from 18 952 to 17 084.
The instrument set review resulted in an estimated savings of $35 665 in sterile
processing costs for the OHNS department. Instrument review applied to all 10
surgical specialties at the institution would result in an estimated annual
savings of $425 378. Through effective leadership, multidisciplinary
participation of all key stakeholders, and a systematic approach, this study
demonstrates that a hospital-wide quality improvement intervention for instrument
set optimization can be successfully performed in a large, multisite tertiary
care academic hospital.
PMID- 29936864
TI - Guided Intra-articular Corticosteroid Injections in the Midfoot.
AB - BACKGROUND: Intra-articular corticosteroid injections are used for both their
therapeutic and diagnostic function. There is a paucity of literature
investigating the efficacy of intra-articular corticosteroid injections into the
midfoot. The aim of the study was to identify the efficacy of image guided intra
articular corticosteroid (Methylprednisolone) injections for midfoot
osteoarthritis The null hypothesis of this study was there would be no benefit or
increase of the Self-reported Foot and Ankle Score (SEFAS) from an intra
articular corticosteroid injection. METHODS: SEFAS was collected at 4 and 12
months postinjection. A total of 37 consecutive patients who had 67 midfoot
injections were recruited into the study over a 6-month period. RESULTS: The mean
SEFAS score preinjection was 17.0, at 4 months postinjection was 31.8 ( P <
.001), and 12 months postinjection 21.3 ( P < .14). There was a statistically
significant improvement in postinjection SEFAS ( P < .001) at 4 months. The null
hypothesis of this study was rejected. Response to the injection was varied but
patients with BMI less than 30 had a sustained ( P < .04) symptomatic improvement
at 12 months when compared to the obese patients. CONCLUSION: Our findings
support the use of corticosteroid injections as a viable diagnostic and
therapeutic option following failed conservative treatment options prior to
operative intervention. The results at 4 months were statistically significant
with an additional finding of a difference observed between obese and nonobese
patients. This may have implications for further educating the patient in
effective weight loss that may improve symptom relief from intra-articular
injection. LEVEL OF CLINICAL EVIDENCE: Level III, comparative study.
PMID- 29936863
TI - Early Presence of HIV-1 Subtype C in Washington, D.C.
AB - The presence of non-B HIV subtypes in the USA has been documented during the
epidemic, although the timing of early introductions of different subtypes
remains uncertain. Subtype C, the most common HIV variant worldwide, was first
reported in the USA in 1996-97, after subtype C had expanded greatly in sub
Saharan Africa. In this study, we report a patient with subtype C infection
acquired by mother-to-child transmission, born in the USA in 1990 to a
Washington, D.C. resident who never traveled outside the USA, demonstrating that
subtype C was present in the USA much earlier. Comparative analysis of the
sequence from this patient and subtype C sequences in the USA and elsewhere
suggest multiple independent introductions of this subtype into the USA have
taken place, many of which are traced to sub-Saharan or East Africa. These data
indicate subtype C HIV was already present in the USA years earlier than
previously reported, and during the early period of subtype C expansion.
PMID- 29936865
TI - Correlation between symptoms and functioning in psychiatric patients and temporal
patterns of medication refills derived from pharmacy prescription claims.
AB - OBJECTIVES:: Pharmacy dispensing claims data provide longitudinal records of
prescriptions and refill events. Previous studies in psychiatric patients have
utilised these data to derive indicators of medication adherence based on
information regarding the amount of medication supplied and its dosage. An
alternative approach was developed in which the regularity of medication refill
events was analysed as a potential indicator of psychiatric patient symptoms and
functioning. METHODS:: A method to quantify the regularity of medication refills
was developed and subsequently used to investigate how the resulting regularity
index (RI), derived from retrospective prescription refill records, correlated
with symptomatic and functional assessments of 89 psychiatric patients after
adjusting for covariates. RESULTS:: A two-step hierarchical regression model
indicated that variances explained by prior hospitalisation and the RI were
significant for patient scores on the Kessler 10 Psychological Distress Scale
(K10), standard beta value 0.22, p < 0.05, for the SF-12 MC, standard beta value
0.31, p < 0.01, and the Work and Social Adjustment Scale (WSAS), standard beta
value 0.31, p < 0.01. CONCLUSIONS:: This method to quantify the regularity of
medication refills using prescription supply date alone may provide valuable
information about patients' symptoms and functioning.
PMID- 29936866
TI - Costs of relapsed diffuse large B-cell lymphoma among Medicare patients.
AB - While health care costs can be considerable in individuals with diffuse large B
cell lymphoma (DLBCL), the degree to which health care expenditures vary
following first-line treatment for non-relapsed versus relapsed DLBCL is unknown.
Using 100% Medicare claims, we identified beneficiaries with DLBCL treated with
first-line therapy between 1 January 2010 and 30 June 2014. We then compared
health care expenditures of patients who received a second-line
immunochemotherapy (relapse cohort) to those who did not begin a second-line
therapy during follow-up (non-relapse cohort). After propensity score matching,
the relapsed cohort incurred significantly higher health care costs ($6998 vs
$3314 per month; p < .001), driven by inpatient ($2548 vs $1943 per month; p <
.001) and outpatient office visit costs ($3581 vs $753 per month; p < .001). Our
analysis confirms older adults with relapsed DLBCL incur higher medical costs and
suggests improved first-line treatment would not only reduce the likelihood of
relapse, but also contain health care costs.
PMID- 29936867
TI - Progress in gene and cell therapies for the neuronal ceroid lipofuscinoses.
AB - INTRODUCTION: The neuronal ceroid lipofuscinoses (NCLs) are a subset of lysosomal
storage diseases (LSDs) that cause myoclonic epilepsy, loss of cognitive and
motor function, degeneration of the retina leading to blindness, and early death.
Most are caused by loss-of-function mutations in either lysosomal proteins or
transmembrane proteins. Current therapies are supportive in nature. NCLs
involving lysosomal enzymes are amenable to therapies that provide an exogenous
source of protein, as has been used for other LSDs. Those that involve
transmembrane proteins, however, require new approaches. Areas covered: This
review will discuss potential gene and cell therapy approaches that have been,
are, or may be in development for these disorders and those that have entered
clinical trials. Expert opinion: In animal models, gene therapy approaches have
produced remarkable improvements in neurological function and lifespan. However,
a complete cure has not been reached for any NCL, and a better understanding of
the limits of the current crop of vectors is needed to more fully address these
diseases. The prospects for gene therapy, particularly those that can be
delivered systemically and treat both the brain and peripheral tissue, are high.
The future is beginning to look bright for NCL patients and their families.
PMID- 29936868
TI - Renal denervation achieved by endovascular delivery of ultrasound in RADIANCE-HTN
SOLO or by radiofrequency energy in SPYRAL HTN-OFF and SPYRAL-ON lowers blood
pressure.
PMID- 29936869
TI - Eurasianism versus IndoGermanism: Linguistics and mythology in the 1930s'
controversies over European prehistory.
AB - In 1935, the Russian linguist Prince Nicolai S. Trubetskoi and the French
mythologist Georges Dumezil engaged in a vicious debate over a seemingly obscure
subject: the structure of Northwest Caucasian languages. Based on unknown
archival material in French, German, and Russian, this essay uses the debate as a
pathway into the 1930s scientific and political stakes of IndoEuropeanism - the
belief that European cultures emerged through the spread of a single IndoEuropean
people out of a single "motherland." Each of the two authors held strong
commitments to visions of European order and its origins - in "Eurasia" for
Trubetskoi and a Northern European Heimat for Dumezil. The North Caucasus, long a
privileged site for Russian and European scholars, now became key to the
renegotiation of the origins and reach of imagined prehistoric IndoEuropean
conquerors, but also the 1930s' debate over the value of different disciplines
(linguistics, mythology, archaeology, folklore studies) for the origins of
language, myth, and the European deep past. As a moment in the history of modern
speculations about prehistory, pursued in the shadow of Nazi scholarship, the
debate transformed fields of research - notably linguistics, comparative
mythology, and structuralism - and the assumptions about the shape of Europe.
PMID- 29936870
TI - Polyacanthoside A, a new oleanane-type triterpenoid saponin with cytotoxic
effects from the leaves of Acacia polyacantha (Fabaceae).
AB - The chemical investigation of the leaves and stem bark of Acacia polyacantha
(Fabaceae) led to the isolation of a new oleanane-type triterpenoid saponin named
polyacanthoside A 1 together with fifteen known compounds. Their structures were
established from spectral , mainly HRESIMS, 1D NMR and 2D NMR and by comparison
with literature data. The cytotoxicity of compound 1 and the analogues 8 as well
as doxorubicin was determined in a panel of 9 cancer cell lines including
sensitive and drug resistant phenotypes. Unlike the analogue 8, compound 1 as
well as doxorubicin displayed cytotoxic effects in all the 9 tested cancer cell
lines with IC50 values ranged from 8.90 MUM (towards CCRF-CEM leukemia cells) to
35.21 MUM (towards HepG2 hepatocarcinoma cells) for compound 1 and from 0.02 MUM
(towards CCRF-CEM leukemia cells) to 66.83 MUM (against CEM/ADR5000 leukemia
cells) for doxorubicin.
PMID- 29936871
TI - Regulatory convergence of medical devices: a case study using ISO and IEC
standards.
AB - INTRODUCTION: Achieving regulatory convergence is important in providing safe and
effective medical devices to patients in a timely manner. The use of standards
set by the International Organization for Standardization (ISO) and the
International Electrotechnical Commission (IEC), may be an important tool for
regulatory convergence. The International Medical Device Regulators Forum (IMDRF)
published a survey and statements regarding the use of these standards in each
IMDRF jurisdiction, which showed that each jurisdiction proactively uses these
standards in its regulation. Areas covered: This review describes the current
situation by comparing the ISO and IEC standards with regulations in the European
Union, the USA, and Japan on the basis of third-party certification in Japan.
Expert Commentary: Our results show that ISO and IEC standards may be important
tools for regulatory convergence. However, the corresponding Technical Committees
and publication editions vary in each regulation. Furthermore, there are cases in
which inconsistencies between the requirements of these standards and regulation
may arise. Considering this background, it is important that jurisdictions have
common consensus about which Technical Committees are appropriate for the
regulation of medical devices and the importance of involving standards
development at an early stage to reflect regulatory opinions.
PMID- 29936872
TI - Atorvastatin-loaded lipid nanoparticles: antitumor activity studies on MCF-7
breast cancer cells.
AB - Atorvastatin is a synthetic statin commonly used in the treatment of
hypercholesterolemia. Apart from this, statins appear to have pleiotropic
effects, including modulation of cell growth, apoptosis. Through modulation of
these pathways, statins have the potential to influence a wide range of disease
processes, including cancer. However, poor aqueous solubility (0.1 mg/mL) and
poor oral bioavailability has limited therapeutic application of atorvastatin.
Present work is an attempt to improve tumor targeting of atorvastatin by
incorporating in nanostructured lipid carriers (NLCs) and studying its anticancer
activity on MCF-7 cell lines. NLCs of atorvastatin were formulated by high-speed
homogenization followed by probe sonication method. The optimized batch of NLCs
had a mean size of 130.02 +/- 3.1 nm and entrapment efficiency of 90.42 +/- 3.7%.
The in vitro drug release study by dialysis method indicated that drug entrapped
in the NLCs remains entrapped at acidic pH as well as in phosphate buffer of pH
7.4 for a prolonged period of time as compared to plain drug. In vitro
cytotoxicity studies on MCF-7 (mammary adenocarcinoma human cell lines) cell
lines showed that concentration of drug required for total growth inhibition
(TGI) and 50% growth inhibition (GI50) of MCF-7 cells was found to be 27.4 ug/mL
and <10 ug/mL respectively, in case of atorvastatin- NLCs which is less than that
required in case of plain atorvastatin and almost similar to that of adriamycin.
All these findings reinforce the fact that atorvastatin loaded NLCs are promising
novel delivery system for treating breast cancer.
PMID- 29936873
TI - Relationship between knee alignment in asymptomatic subjects and flexibility of
the main muscles that are functionally related to the knee.
AB - Objective To assess the relationship between static frontal knee alignment in
asymptomatic subjects and flexibility of the main muscles functionally related to
the knee. Methods A descriptive cross-sectional study was performed in 33 healthy
adults (19-31 years). The frontal knee angle (valgus/varus angle) was measured by
photogrammetry and it was measured in the lateral side. Therefore, high values
were assigned for genu varum and low values for genu valgum. Iliopsoas, gluteus
maximus and medius, rectus femoris, biceps femoris, vastus of the quadriceps, and
gastrocnemius muscles were stretched. Muscles were classified as normal, reflex
hypomobile, or structural hypomobile. Results Women had significantly greater
valgus than did men (right angle, women: 174.41 degrees /men: 177.41 degrees ;
left angle, women: 174.20 degrees /men: 178.70 degrees ). The right frontal plane
knee angle was higher in women with structural hypomobile vastus. The left
frontal plane knee angle was higher in women with structural hypomobile
iliopsoas. No relationships were found in men. Conclusions A tighter vastus of
the quadriceps and tighter iliopsoas are related to greater genu varum in adult
women. Stretching the vastus of the quadriceps and iliopsoas when there is a
tendency for excess varus in the knee, to prevent overuse injury or early
osteoarthritis, might be clinically relevant.
PMID- 29936874
TI - Amphotericin B-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid
carrier (NLCs): effect of drug loading and biopharmaceutical characterizations.
AB - The aim of this study was to further investigate the effect of drug loading, drug
entrapment efficiency, the drug release profiles and biopharmaceutical point of
views of amphotericin B (AmB) lipid formulations, that is, degree of aggregation
by UV-spectroscopy, in vitro hemolytic and antifungal activities. The optimum
drug loading was 2.5% by weight corresponded to lipid fraction in formulation.
Increasing of the drug entrapment was achieved by blending small amount of
phospholipid in solid lipid nanoparticle (SLN) dispersions. All AmB lipid
dispersions were less aggregated species and hemolytic response than Fungizone(r)
indicating that lipid nanoparticles could reduce its toxicity. The sustained
release profiles of AmB formulations depended on its aggregated form and
entrapment efficiency. Too high AmB loaded (5% w/w) showed a biphasic drug
release profile probably due to some amounts of drug deposited on the nanosphere
surface including in continuous phase which promptly released. For in vitro
antifungal testing, all AmB lipid formulations were equal and more effective than
both AmB itself and Fungizone(r). These observations suggested that AmB loaded
SLNs, nanostructured lipid carriers and modified SLNs by blending lecithin could
enhance AmB solubility, prolong release characteristics, reduce toxicity and
improve antifungal activity.
PMID- 29936876
TI - Role of Dimensionality in Predicting the Spontaneous Behavior of the Brain Using
the Classical Ising Model and the Ising Model Implemented on a Structural
Connectome.
AB - There is accumulating evidence that spontaneous fluctuations of the brain are
sustained by a structural architecture of axonal fiber bundles. Various models
have been used to investigate this structure-function relationship. In this work,
we implemented the Ising model using the number of fibers between each pair of
brain regions as input. The output of the Ising model simulations on a structural
connectome was then compared with empirical functional connectivity data. A
simpler two-dimensional classical Ising model was used as the baseline model for
comparison purpose. Thermodynamic properties, such as the magnetic susceptibility
and the specific heat, illustrated a phase transition from an ordered phase to a
disordered phase at the critical temperature. Despite the differences between the
two models, the lattice Ising model and the Ising model implemented on a
structural connectome (the generalized Ising model) exhibited similar patterns of
global properties. To study the behavior of the generalized Ising model around
criticality, calculation of the dimensionality and critical exponents was
performed for the first time, by introducing a new concept of distance based on
structural connectivity. Same value inside the fitting error was found for the
dimensionality in both models suggesting similar behavior of the models around
criticality.
PMID- 29936877
TI - Usefulness of metagenomic analysis in differential diagnosis for pyoderma
gangrenosum.
AB - Pyoderma gangrenosum (PG) is a rare ulcerative inflammatory dermatosis easily
confused with wound infection following surgery. There have been seven case
reports of PG occurring after total knee arthroplasty (TKA), all of which used
routine tissue culture for differential diagnosis. Notably, all previous cases
involved delayed diagnosis. We report a case of PG after TKA where we used
shotgun metagenomics for differential diagnosis. Metagenomic analysis is a new
method that can be used for pathogen detection; it is fast and sensitive,
compared with traditional culture. Early application of metagenomic analysis in
cases of suspicious wound infection after surgery can detect the pathogen of the
infection for target therapy; it can also exclude infection for differential
diagnosis of non-infectious diseases, such as autoimmune disorders. This case is
presented to support the use of metagenomic analysis by surgeons and physicians
for early and rapid differential diagnosis in patients who exhibit postoperative
wound infections.
PMID- 29936878
TI - Future applications of FGF/FGFR inhibitors in cancer.
AB - INTRODUCTION: Deregulation of the fibroblast growth factor (FGF)/FGF receptor
(FGFR) network occurs frequently in tumors due to gene amplification, activating
mutations, and oncogenic fusions. Thus, the development of FGF/FGFR-targeting
therapies is the focus of several basic, preclinical, and clinical studies. Areas
covered: This review will recapitulate the status of current FGF/FGFR-targeted
drugs. Expert commentary: Non-selective FGF/FGFR inhibitors have been approved
for cancer treatment but evidence highlights various complications affecting
their use in the clinical practice. It appears mandatory to identify FGF/FGFR
alterations and appropriate biomarkers that may predict and monitor response to
treatment, to establish the contribution of the FGF/FGFR system to the onset of
mechanisms of drug resistance, and to develop effective combinations of FGF/FGFR
inhibitors with other targeted therapies.
PMID- 29936879
TI - Treatment and outcomes of urethral recurrence after orthotopic neobladder
replacement in patients with bladder cancer - practice in a single centre.
AB - Objectives To report on the treatment of urethral recurrence after orthotopic
urinary diversion at our institution. Methods We retrospectively reviewed
clinical information of urethral recurrence in patients who underwent radical
cystectomy and orthotopic urinary diversion between January 1998 and January
2013. Results Of 341 patients, 282 presented for follow-up (median follow-up: 56
months; range: 1-174 months). Eight patients developed local recurrence of
urothelial cancer after radical cystectomy. The rate of urethral recurrence
(1.4%) in female patients who underwent orthotopic urinary diversion was lower
than in male patients (3.3%). The median (range) time to recurrence was 33 (6
120) months after radical cystectomy and orthotopic urinary diversion.
Recurrences were treated by transurethral resection of tumour, urethrectomy,
neobladder resection, revision of urinary diversion, adjuvant chemotherapy, or
radiation therapy, based on individual circumstances. Survival analysis showed
that 5-year cancer-specific survival was significantly higher in patients with
urethral recurrence alone (83.3%), compared with patients with other recurrences,
including pelvic/abdomen recurrence and distant metastasis (26.8%). Conclusions
En bloc urethrectomy and revision of urinary diversion remain the principle
surgical choices. Selection of transurethral tumour resection was based on tumour
stage and was used in carefully chosen patients. Cancer-specific survival might
depend on multidisciplinary therapy.
PMID- 29936880
TI - Brain Network Connectivity and Executive Function in Long-Term Survivors of
Childhood Acute Lymphoblastic Leukemia.
AB - Chemotherapeutic agents used to treat acute lymphoblastic leukemia (ALL), the
most common cancer affecting young children, have been associated with long-term
cognitive impairments that reduce quality of life. Executive dysfunction is one
of the most consistently observed deficits and can have substantial and pervasive
effects on academic success, occupational achievement, psychosocial function, and
psychiatric status. We examined the neural mechanisms of executive dysfunction by
measuring structural and functional connectomes in 161 long-term survivors of
pediatric ALL, age 8-21 years, who were treated on a single contemporary
chemotherapy-only protocol for standard/high- or low-risk disease. Lower global
efficiency, a measure of information exchange and network integration, of both
structural and functional connectomes was found in survivors with executive
dysfunction compared with those without dysfunction (p < 0.046). Patients with
standard/high- versus low-risk disease and those who received greater number of
intrathecal treatments containing methotrexate had the lowest network
efficiencies. Patients with executive dysfunction also showed hyperconnectivity
in sensorimotor, visual, and auditory-processing regions (p = 0.037) and poor
separation between sensorimotor, executive/attention, salience, and default mode
networks (p < 0.0001). Connectome disruption was consistent with a pattern of
delayed neurodevelopment that may be associated with reduced resilience,
adaptability, and flexibility of the brain network. These findings highlight the
need for interventions that will prevent or manage cognitive impairment in
survivors of pediatric acute lymphoblastic leukemia.
PMID- 29936881
TI - Prognostic roles of preoperative CT findings and air-bone gaps in type 1
tympanoplasty.
AB - BACKGROUND: Although CT has been used widely, the role of preoperative CT
findings including other factors in tympanoplasty has not been elucidated
comprehensively. AIMS/OBJECTIVES: To evaluate relationship of CT findings with
other factors and audiological results in type 1 tympanoplasty. MATERIAL AND
METHODS: A cohort of consecutive 175 patients with type 1 tympanoplasty was
enrolled. Addition of mastoidectomy was based on the presence of soft tissue in
antrum on CT. Postoperative air-bone gap (ABG) and reperforation rate were
analyzed. RESULTS: Positive soft tissue in antrum on CT was found in 52 (29.7%)
patients and showed larger preoperative ABG than the negative group. Successful
ABG closure (<=20 dB) was obtained in 97% when preoperative ABG <=20 dB, but it
decreased as the preoperative ABG increased (83% with preoperative ABG of 21-30
dB, and 0% with preoperative ABG >30 dB). Postoperative reperforation rate was
positively related to the preoperative ABG, but not the presence of soft tissue
in the antrum, the size, or locations of preoperative perforations. CONCLUSIONS
AND SIGNIFICANCE: Our findings showed that temporal bone CT was helpful in
determining addition of mastoidectomy and the presence of soft tissue in the
antrum was associated with large ABG.
PMID- 29936882
TI - Uric acid level may not be reduced in essential tremor.
AB - BACKGROUND: Essential tremor is very common, but characterization is difficult
because of its heterogeneity. Neuropathology is important to elucidate the
characteristics of neurological disorders. However, pathological findings in
essential tremor have been inconsistent among studies. Uric acid is a strong
antioxidant and might be a biomarker in neurodegenerative process. We
hypothesized that uric acid level would be reduced if essential tremor is a
neurodegenerative disease. Our aim was to compare uric acid level between
essential tremor patients and healthy individuals. METHODS: This was a
prospective, case-control, multicenter study with 92 essential tremor patients
and 77 healthy subjects. For homogeneity, the essential tremor group was
subdivided into two groups (hereditary and sporadic). Clinical and laboratory
findings were compared among the essential tremor and healthy groups. RESULTS:
The demographic characteristics were comparable among the groups. The uric acid
level was lower in the essential tremor group than in healthy subjects, but the
difference did not reach statistical significance. There was a negative
correlation between uric acid level and disease duration in the hereditary group
(p = .046) and between uric acid level and age at onset in the sporadic group (p
= .012). The mean values of total cholesterol were significantly lower in the
sporadic group than in the other groups (p = .011). Total cholesterol was
positively correlated with age at onset in the hereditary essential tremor group
(p = .010). CONCLUSIONS: We did not find any evidence that uric acid levels
suggested essential tremor is a neurodegenerative disease. However, further
research with more patients might be needed given the negative correlations of
disease duration and age at onset with uric acid level.
PMID- 29936883
TI - Morphine reverses the effects of 1-methyl-4-phenylpyridinium in PC12 cells
through activating PI3K/Akt.
AB - AIM OF THE STUDY: Parkinson's disease (PD) is a neurodegenerative disorder. It is
caused by the degeneration of dopaminergic neurons and the dopamine (DA) deletion
in the substantia nigra pars compacta (SNpc). Morphine elevates the level of
dopamine in the mesolimbic dopamine system and plays a role in alleviating PD
symptoms. However, the molecular mechanism is still unclear. The aim of the study
is to investigate the mechanism on morphine alleviating PD symptoms. MATERIALS
AND METHODS: The viability of PC12 cells was measured by using MTT assay. The
expressions of tyrosine hydroxylase (TH), thioredoxin-1 (Trx-1), CyclinD1 and
Cyclin-dependent kinase5 (Cdk5) were detected by Western Blot. RESULTS: In
present study, we found that morphine increased the cell viability in PC12 cells.
1-methyl-4-phenylpyridi-nium (MPP+) reduced the cell viability and TH expression,
which were reversed by morphine. MPP+ decreased the expressions of Trx-1,
CyclinD1, Cdk5, which were restored by morphine. Moreover, the role of morphine
in restoring the expressions of Trx-1, CyclinD1 and Cdk5 decreased by MPP+ was
abolished by LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor.
CONCLUSIONS: These results suggest that morphine reverses effects induced by MPP
p through activating PI3K/Akt pathway.
PMID- 29936884
TI - Human and Rat Bone Marrow-Derived Mesenchymal Stem Cells Differ in Their Response
to Fibroblast Growth Factor and Platelet-Derived Growth Factor.
AB - Tissue engineering requires large numbers of cells with enhanced differentiation
properties. Thus, the effect of expansion conditions must be explored. Human and
rat marrow-derived mesenchymal stem cells (hMSCs and rMSCs, respectively) were
comparatively culture expanded through seven passages in the presence of either
fibroblast growth factor-2 (FGF-2) or platelet-derived growth factor BB (PDGF
BB). Proliferation of both hMSCs and rMSCs was enhanced by FGF-2 and PDGF-BB.
Population doubling times for hMSCs were 2.4 days for control and 1.75 and 2.0
days for FGF-2 and PDGF-BB, respectively, and 3.25, 3.06, and 2.95 days for
rMSCs. Supplementation with FGF-2 during cell expansion resulted in significantly
greater in vivo bone formation for hMSCs. Use of PDGF-BB resulted in greater bone
formation than that observed for control conditions, but the differences were
only significant for P1. For rMSCs, significant increases in bone formation were
noted in either FGF-2 or PDGF-BB expanded cells implanted at P4 or P7, but not
for P1. Under in vitro osteogenic stimulation, calcium content was elevated and
bone matrix deposition was enhanced for P1 and P7 rMSCs expanded with FGF-2.
Although culture conditions, including FBS, were held constant, these
observations suggest that medium must be optimized separately for each species of
MSCs.
PMID- 29936885
TI - Peripherally inserted central catheter with intracavitary electrocardiogram
guidance: Malposition risk factors and indications for post-procedural control.
AB - OBJECTIVES: To confirm the feasibility of intracavitary electrocardiogram
guidance to verify tip's position during insertion of peripherally inserted
central catheter and to identify clinical factors or intracavitary
electrocardiogram patterns associated with aberrant tip's position. METHODS: A
prospective study was conducted in our university hospital after authorization of
the ethics committee. All patients addressed for peripherally inserted central
catheter insertion were included and received the insertion using intracavitary
electrocardiogram and electromagnetic guidance. Side of insertion and three
electrocardiogram factors were collected: visualization of P-wave at baseline
(sinusal rhythm), acquisition of the maximal P-wave and the negative deflection.
All patients had a systematic post-procedural chest X-ray. One of the
investigators assessed all chest X-ray, blinded to the results of intracavitary
electrocardiogram, and confirmed whether the tip's position on chest X-ray
matched with the intracavitary electrocardiogram information or if the tip was
malpositioned on chest X-ray (mismatch with intracavitary electrocardiogram or
aberrant position). Factors associated with malposition were described. RESULTS:
From January 2015 to April 2015, 330 patients were eligible, 5 had an
uninterpretable chest X-ray, and 14 were non-sinusal at baseline. Our main
analysis population included 311 patients. We observed a mismatch between
intracavitary electrocardiogram and chest X-ray estimate of the tip's position in
3 cases (1%) and an aberrant tip's position occurred in 3 cases (1%). Incidence
of malposition was higher in the group of patients with non-sinusal rhythm (14%)
and when the catheter was inserted on the left side (7%). CONCLUSION: This study
confirmed the feasibility of intracavitary electrocardiogram for peripherally
inserted central catheter positioning and the limits of chest X-ray. Insertion on
left side may represent risk factor for aberrant position but our study lacked
power to establish a statistical link.
PMID- 29936886
TI - Prices for Physicians' Services in Medicare Advantage and Commercial Plans.
AB - The prices that insurers pay physicians ultimately affect beneficiaries' health
insurance premiums. Using 2014 claims data from three major insurers, we analyzed
the prices insurers paid in their Medicare Advantage (MA) and commercial plans
for 20 physician services, in and out of network, and compared those prices with
estimated amounts that Medicare's fee-for-service (FFS) program would pay for the
same service. MA prices paid by those insurers were close to Medicare FFS prices,
varied minimally, and were similar in and out of network. In contrast, commercial
prices paid by the same insurers were substantially higher than FFS, varied
widely, and were up to three times higher out of network than in network. Those
results suggest that insurers can use statutory limits on out-of-network charges
in MA to negotiate lower in-network prices in those plans. In contrast, without
those limits on out-of-network prices, in-network prices in commercial plans are
much higher.
PMID- 29936887
TI - Commentary: Outcomes of Endovascular Aneurysm Sealing According to the Revised
Nellix Instructions for Use: The Impact on Complications Is Not Yet Apparent.
PMID- 29936888
TI - Commentary: How to Deal With Air Released From Thoracic Endografts: Ignore It or
Fear It?
PMID- 29936889
TI - SLA-11 mutations are associated with litter size traits in Large White and
Chinese DIV pigs.
AB - Litter size is an important economic traits in pigs. SLA-11 gene is a member of
SLA (swine leukocyte antigen) complex. In our previous study, the SLA-11 gene was
differentially expressed in PMSG-hCG stimulated preovulatory ovarian follicles of
Chinese Taihu and Large White sows. Here, we identified two mutations (c.754-132
T > C and c.1421 + 38 T > C) in SLA-11 gene and analyzed the associations of two
SNPs with litter size traits in Large White (n = 263) and DIV (n = 117) sows. The
results showed that in Large White pigs, SLA-11 c.754-132 CC sows produced 0.74
and 0.87 more pigs per litter for TNB and NBA of all parities than did TT sows (p
< .05); In DIV pigs, SLA-11 c.754-132 CC sows produced 1.17 more pigs per litter
for TNB of all parities than did TC sows (p < .05). In Large White pigs, SLA-11
c.1421 + 38 CC sows produced 0.9 more pigs per litter for TNB of all parities
than did TT sows (p < .05), while in DIV pigs SLA-11 c.1421 + 38 CC sows produced
0.84 and 0.7 less pigs per litter for TNB and NBA of all parities than did TT
sows (p < .05). Our research indicated that SLA-11 mutations were potential
molecular markers for improving the litter size traits in pigs.
PMID- 29936890
TI - Women's Cigarette and Marijuana Use in Pregnancy: Identifying the Role of Past
Versus Recent Violence Exposure.
AB - Both cigarette smoking and marijuana use during pregnancy pose serious risks to
healthy fetal development, yet little is known about the comparative contribution
of recent versus past traumatic experiences to women's smoking behavior. The
current study aimed to examine the relative contributions of childhood adversity
and past year intimate partner violence (IPV) to women's cigarette and marijuana
use during pregnancy in a high-risk, low-income sample. Participants ( n = 101)
were interviewed to evaluate past year IPV, childhood adversity, and cigarette
and marijuana use. Results indicated that approximately one in four pregnant
women in the sample reported that they were currently smoking cigarettes. Only a
minority of those who reported prepregnancy smoking (22.5%) were able to quit
smoking once pregnant. Regarding marijuana use, 6.9% of women reported use during
pregnancy, with 68.1% of women using prior to pregnancy ceasing use once
pregnant. Results of multinomial regressions controlling for income and education
indicated that past year physical abuse by a partner was associated with light
cigarette use during pregnancy whereas high rates of childhood adversity were
associated with moderate cigarette use during pregnancy. Sexual IPV was
associated with marijuana use during pregnancy. Comprehensive assessment of
women's history of exposure to violence, including both past and recent exposure,
provides insight into which women may have the most difficulty with unassisted
cessation in the prenatal period. Providing better intervention and support
around cigarette and marijuana cessation for women exposed to violence is a
critical need, especially among groups that are at sociodemographic risk for
substance use in pregnancy.
PMID- 29936891
TI - Differentiating Autism Spectrum Disorder From ADHD Using the Social Communication
Questionnaire.
AB - OBJECTIVE: This study examined the ability of the Social Communication
Questionnaire (SCQ) to differentiate between autism spectrum disorder (ASD),
ADHD, and typically developing (TD) children. METHOD: Children ( Mage = 11.27
years, SDage = 3.28) identified with ASD Severity Levels "1" and/or "2" ( n =
28), ADHD ( n = 44), dual diagnoses of ADHD and ASD ( n = 29), and TD ( n = 61)
were assessed using the SCQ. RESULTS: The SCQ differentiated between ASD and non
ASD groups. Children with ASD had higher total and domain scores on the SCQ than
ADHD and TD children. The optimal cutoff total score of 13 was identified for
differentiating between ASD and ADHD groups (area under the curve [AUC] = .96).
Twenty eight of the 39 items were identified as significant in differentiating
between ASD and ADHD. CONCLUSION: The SCQ continues to be a well-validated
screening tool for ASD and is suitable for determining whether further ASD
assessment is warranted in children with ADHD symptoms.
PMID- 29936892
TI - Effect of Tumor Size and Minimal Extrathyroidal Extension in Patients with
Differentiated Thyroid Cancer.
AB - INTRODUCTION: Risk-stratified treatment strategies have become a focus in the
treatment of differentiated thyroid cancer (DTC). In the 2015 American Thyroid
Association treatment guidelines, adjuvant treatment with radioactive iodine
(RAI) is considered in the presence of minimal extrathyroidal extension (mETE).
This study aimed to investigate the prognostic significance of mETE and tumor
size in patients with DTC. METHODS: A retrospective review was undertaken of 2323
consecutive patients treated surgically for T1-T3 (defined per seventh edition of
the American Joint Committee on Cancer staging criteria) and M0 DTC from 2000 to
2015 at The University of Texas MD Anderson Cancer Center. Patients were divided
into four groups according to the size of the tumor (<=4 cm vs. >4 cm) and the
presence of mETE. Predictors of disease-free survival (DFS), disease-specific
survival, locoregional failure (LRF), and distant metastatic failure (DMF) were
compared using the log-rank test and Cox's proportional hazards models. RESULTS:
There were only seven DTC-related deaths, limiting the clinical significance of
the analysis, especially of overall and disease-specific survival. Following
multivariate analysis, patients with tumors >4 cm did worse than patients with
tumors <=4 cm with respect to DFS (group 3 [>4 cm without mETE] adjusted hazard
ratio (HRadj) = 2.1 [confidence interval (CI) 1.1-3.8]; group 4 [>4 cm with mETE]
HRadj = 2.9 [CI 1.6-5.1]). However, patients did not differ according to DFS,
regardless of the presence of mETE within each size category (group 2 [<=4 cm
with mETE] vs. group 1 [<=4 cm without mETE] HRadj = 1.3 [CI 0.9-1.8]; group 4
[>4 cm without mETE] vs. group 3 [>4 cm with mETE] HRadj = 1.0 [CI 0.5-2.3]). For
LRF and DMF, size but not mETE was also an independent risk factor. CONCLUSION:
Tumor size, but not the presence of mETE, was an independent predictor of DFS,
LRF, and DMF in DTC.
PMID- 29936893
TI - Resisting Unwanted Sexual and Social Advances: Perspectives of College Women and
Men.
AB - This study examines college men's ( N = 635) and women's ( N = 650) reports of
women's resistance against unwanted sexual and social advances. Men completed
surveys to assess (a) initiation of unwanted sexual contact with a female
partner, (b) initiation of unwanted sexual intercourse with a female partner, (c)
sexual situations where a female partner decided she did not want to proceed, (d)
encouraging a woman to drink when they were aware that the woman did not want to,
and (e) attempting to take a woman to an isolated location against her will.
Women completed corresponding questionnaires regarding the receipt of such
unwanted advances, the outcome of the situation, and the resistance tactics
utilized. Many men (5%-46%) and women (15%-38%) initiated or experienced,
respectively, at least one of the five unwanted sexual or social advances.
Unwanted sexual and social advances most often stopped as a result of women's
verbal and physical resistance. Few advances (0%-8%) stopped as a result of
bystander intervention. In addition to decreasing men's likelihood of engaging in
unwanted sexual and social advances, these data highlight the importance of
educating women on the effectiveness of verbal and physical resistance tactics,
and increasing the frequency of prosocial bystander action on college campuses.
PMID- 29936894
TI - Genomic instability and DNA replication defects in progeroid syndromes.
AB - Progeroid syndromes induced by mutations in lamin A or in its interactors - named
progeroid laminopathies - are model systems for the dissection of the molecular
pathways causing physiological and premature aging. A large amount of data, based
mainly on the Hutchinson Gilford Progeria syndrome (HGPS), one of the best
characterized progeroid laminopathy, has highlighted the role of lamins in
multiple DNA activities, including replication, repair, chromatin organization
and telomere function. On the other hand, the phenotypes generated by mutations
affecting genes directly acting on DNA function, as mutations in the helicases
WRN and BLM or in the polymerase poldelta, share many of the traits of progeroid
laminopathies. These evidences support the hypothesis of a concerted implication
of DNA function and lamins in aging. We focus here on these aspects to contribute
to the comprehension of the driving forces acting in progeroid syndromes and
premature aging.
PMID- 29936895
TI - Refugees and Migrants in Greece: An Ethnographic Reflective Case Study.
AB - INTRODUCTION: Greece has experienced a double challenge of being under austerity
for the past decade and also facing an influx of refugees and migrants (R&Ms),
mostly fleeing war zones. The purpose of this case study is to report on a
shelter camp in Greece. METHOD: An ethnographic case study technique was used.
Data were collected via interviews, personal observations, and field notes.
Analytic themes based on the coded data and personal memo writing were created.
The sample consisted of the shelter camps' living social reality. RESULTS:
Analysis revealed five thematic categories: ground rules, makeshift layout, food
and drinks, children, and nursing perspectives. These were subsequently collated
into a coherent "story" about routine daily life in the shelter camp. DISCUSSION:
As camp facilities had been hastily erected, the services were basic and life was
harsh. The need to provide better facilities including social and psychological
support for R&Ms is evident for this particular host facility. IMPLICATIONS FOR
PRACTICE: In Greece, R&Ms and staff cooperation is constantly sought as this new
societal arrangement is a highly complex and volatile mix for everybody involved.
Nurses have both a humanistic and a professional duty to be involved and help
out. As the camp was run by the army, one could question the impact on culturally
conflicting care provision.
PMID- 29936896
TI - The Unintended Consequences of Rape Disclosure: The Effects of Disclosure
Content, Listener Gender, and Year in College on Listener's Reactions.
AB - Rape is prevalent on American college campuses. Rape survivors often disclose
their experience to their peers in hope of receiving support and obtaining
justice (i.e., the intended consequences of disclosure). Yet, rape disclosures
may also lead to unintended consequences, such as stigma. How peers react to
survivors' disclosures of rape greatly influences survivors' recovery and their
decision to press charges against their perpetrators. In this article, we explore
gender differences in responses to rape disclosures. Using an experimental design
( N = 391), we investigate reactions to stigmatizing (versus nonstigmatizing)
rape disclosures. We find that, when controlling for the experimental condition,
college men stigmatize the rape survivor more than college women. However, in
response to a stigmatizing (versus nonstigmatizing) rape disclosure, college
women who have been in college longer, compared with college men, have more
stigmatizing reactions toward the person disclosing that information. Their
reactions then predict increased social distance between the recipient of the
disclosure and rape survivors.
PMID- 29936897
TI - The role of ADAM-like decysin 1 in non-eosinophilic chronic rhinosinusitis with
nasal polyps.
AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is classified into
two subtypes: eosinophilic (ECRSwNP) and non-eosinophilic (NECRSwNP). Although
the inflammatory patterns of ECRSwNP have been elucidated, NECRSwNP is poorly
understood. AIMS/OBJECTIVES: The metalloproteinase ADAM-like decysin 1 (ADAMDEC1)
has been reported to play a role in the early stages of the inflammatory
response. We investigated the role of ADAMDEC1 in the pathogenesis of CRSwNP.
MATERIAL AND METHODS: We compared ADAMDEC1 expression in nasal polyp tissue from
CRS patients using immunohistochemistry and RT-qPCR. Macrophages were cultured
and ADAMDEC1 expression was determined at baseline and after exposure to
lipopolysaccharide (LPS). RESULTS: ADAMDEC1 was virtually undetectable in tissues
from control patients but was highly expressed in the NECRSwNP group compared
with the ECRSwNP group. In nasal polyp tissues, ADAMDEC1 was expressed by CD68
positive cells, with a positive correlation between ADAMDEC1-positive and CD68
positive cells, and also between ADAMDEC1 and CD68 mRNA levels. Furthermore,
stimulation of monocyte-derived macrophages with LPS induced ADAMDEC1 expression.
CONCLUSIONS AND SIGNIFICANCE: This study demonstrates that ADAMDEC1 is involved
in the pathogenesis of NECRSwNP, and also bacterial endotoxin signalling in
macrophages; however, the underlying mechanism remains to be elucidated.
PMID- 29936898
TI - Comparison of electrode position between round window and cochleostomy inserting
approaches among young children: a cone-beam computed tomography study.
AB - BACKGROUND: As the two most commonly used approaches for cochlear implants (CIs),
the round-window insertion (RWI) and cochleostomy are still controversial about
which approach is optimal. The lack of visual observation methods makes it
difficult to compare the electrode position between them. OBJECTIVES: To evaluate
and compare the electrode position between RWI and cochleostomy approaches for CI
among young children. MATERIALS AND METHODS: Twenty-four patients (16 male, 8
female) accepting CI and temporal cone-beam computed tomography (CBCT) scan post
operation in our hospital from January 2016 to July 2017 were analyzed
retrospectively. Operative notes and images were used to identify the surgical
technique. Mainly depending on the round-window exposure, 15 cochleae were
performed with RWI and 11 performed with cochleostomy. RESULTS: Mean age, 2.4
(range 0.8-7) years. The CBCT images showed that all the electrode arrays were
located in scala tympani. There were no significantly statistical differences in
the distance between electrode contacts and modiolus (EMI), intracochlear
insertion length and the angle of electrode arrays at the insertion site of the
cochlea. CONCLUSIONS AND SIGNIFICANCE: Both approaches could insert electrodes
into scala tympani satisfactorily. As electrodes and cochlear structures could be
clearly visualized, CBCT can be applied to assess the electrode position
reliably.
PMID- 29936899
TI - Intention to Participate in Group Prenatal Care: Moving Beyond Yes or No.
AB - Group prenatal care (GPNC) is an alternative model to traditional individual care
and may improve public health outcomes. Prior studies suggest that interest in
GPNC varies widely and few studies have examined characteristics predictive of
interest in this model. The purpose of this study was to inform GPNC recruitment
efforts by examining likelihood of participation delineated by characteristics
and GPNC perceptions. Pregnant participants received information about GPNC then
completed a survey measuring demographic, psychosocial, and reproductive
characteristics, likelihood to participate in GPNC, and factors influencing
selections. Respondents expressed varied levels of likelihood to participate in
GPNC; 16.2% low likelihood, 44.9% moderate likelihood, and 38.9% high likelihood.
Characteristics were similar between groups, and thus their use is not
recommended when targeting recruitment efforts. Benefits outweighed barriers and
threats for the high likelihood category, barriers and threats outweighed
benefits for the low likelihood category, and benefits, barriers, and threats
were balanced for the moderate likelihood category. Accurately assessing
likelihood of participating in GPNC efficiently identifies individuals who are
clearly either going to decline or participate, as well as promotes targeted
recruitment efforts directed at those who are ambivalent. Understanding and
addressing perceived benefits, barriers, and threats supports effective GPNC
recruitment.
PMID- 29936901
TI - CIMAvax-EGF, a therapeutic non-small cell lung cancer vaccine.
AB - INTRODUCTION: Lung cancer represents the most common cause of cancer death
worldwide. While the prognosis remains poor, immunotherapy is giving a positive
impact on survival. Cancer vaccines represent a form of active immunotherapy that
historically has given modest results in terms of efficacy. The overexpression of
the EGFR by tumor cells was reported in more than half of cases of lung cancer,
representing a mechanism of cancerogenesis. CIMAvax-EGF, a therapeutic vaccine
for non-small cell lung cancer (NSCLC) developed in Cuba, consists of a human
recombinant EGF able to induce antibodies against the autologous EGF, resulting
in serum EGF withdrawal and lower EGF-EGFR interaction. Area covered: We
critically reviewed the existing literature about CIMAvax-EGF, from the Pilot
studies to the efficacy controlled studies. We also overviewed the ongoing
trials. Expert opinion: CIMAvax-EGF demonstrated to be safe and immunogenic. In a
phase III randomized study CIMAvax-EGF, used as a switch maintenance treatment
after platinum-based chemotherapy, did not significantly improve survival.
Current data are not sufficient to recommend CIMAvax-EGF as a treatment option
for advanced stage NSCLC. Further studies, conducted in a context of worldwide
standardized clinical practice, are needed to better define if a subpopulation of
patients can benefit from the vaccination.
PMID- 29936902
TI - Prospective memory in clinical populations.
AB - OBJECTIVE: Prospective memory (PM) has emerged as a form of episodic memory that
is frequently impaired in a variety of clinical populations. Neuropsychologists
who routinely evaluate these populations are often unaware of the possibility of
PM deficits or the impact these deficits may have on everyday functioning. The
objective of this special issue is to provide an overview of the nature of
prospective deficits in a range of clinical populations, to discuss
neuropsychological assessment techniques, and to critically evaluate management
strategies. METHOD: We solicited papers from established researchers and issued a
general call for papers for the special issue on PM in clinical populations.
RESULTS: We received submissions from the nine authors that we solicited. These
submissions range from developmental disorders, including autism, attention
deficit hyperactivity disorder, and dyslexia; to disorders of adulthood, such as
schizophrenia, HIV, brain injury, and multiple sclerosis; and finally disorders
that tend to occur at older ages, such as Parkinson's disease and mild cognitive
impairment. In addition, we have included four original research articles that
provide novel data on other populations. These are children and adolescents with
22q11.2 deletion syndrome, first-degree relatives of people with schizophrenia,
individuals with mild brain injury, and individuals with idiopathic REM sleep
behavioral disorder. CONCLUSIONS: The issue highlights the need for clinical
neuropsychologists to be aware of the possible existence of deficits in PM in a
variety of clinical populations and the importance of both assessment and
management strategies to reduce the impact on daily life.
PMID- 29936903
TI - Responding to urgency of need: Initial qualitative stage in the development of a
triage tool for use in palliative care services.
AB - BACKGROUND: Palliative care services face the challenge of a workload increasing
in volume and diversity. An evidence-based triage method to assess urgency of
palliative care needs is required to ensure equitable, efficient and transparent
allocation of specialist resources when managing waiting lists. AIM: As the
initial stage of a mixed-method sequential design, this study aimed to explore
palliative care providers' practices and attitudes towards triaging palliative
care needs and their views regarding the implementation of a standardised
approach. DESIGN: A qualitative study was conducted involving focus groups and
interviews. Transcripts were subjected to deductive thematic analysis.
SETTING/PARTICIPANTS: A total of 20 palliative care providers were purposively
sampled to ensure representation across disciplines (primary, specialist;
medicine, nursing and allied health), service types (inpatient, hospital liaison
and community) and locations (metropolitan and rural). RESULTS: A series of
markers of urgency were identified, including physical and psychological
suffering, caregiver distress, discrepancy between care needs and care
arrangements, mismatch between current site of care and desired site of death
when in terminal phase and complex communication needs. Performance status and
phase of disease were reported to be less informative when considered in
isolation. Interpersonal and system-based barriers to the implementation of a
palliative care triage tool were highlighted. CONCLUSION: The process of triage
in the palliative care setting is complex but can be conceptualised using a
limited number of domains. Further research is required to establish the relative
value clinicians attribute to these domains and thus inform the development of an
acceptable and useful evidence-based palliative care triage tool.
PMID- 29936904
TI - Ethics, emotions and culture: Respecting moral diversity.
PMID- 29936905
TI - Evaluation of a Social Norms Sexual Violence Prevention Marketing Campaign
Targeted Toward College Men: Attitudes, Beliefs, and Behaviors Over 5 Years.
AB - The article evaluates the effectiveness of a 5-year social norms sexual violence
prevention marketing campaign designed specifically for men on a large public
university in the Southeastern United States. From 2010 through 2014, 4,158 men
were asked about their self-reported attitudes, beliefs, and behavior related to
sexual violence as well as their perception of their peers' attitudes, beliefs,
and behaviors. Using social norms theory, a social norms marketing campaign was
developed to target highly discrepant attitudes, beliefs, and behaviors. Results
indicate that both self-reported and perception of peer attitudes and beliefs
improved over time, and the discrepancy between the two reduced over time. In
addition, the frequency of positive and prosocial self-reported behavior
increased on five of the six indicators. This study represents a significant
contribution to the literature, as it uses 5 years of data and includes
behavioral indicators to add evidence for the efficacy of targeting
misperceptions of social norms as a mechanism to engage men in gender-based
violence prevention.
PMID- 29936906
TI - Differences between staff groups in perception of risk assessment and risk
management of inappropriate sexual behaviour in patients with traumatic brain
injury.
AB - This research explored staff perceptions of risk assessment and management of
inappropriate sexual behaviour (ISB) displayed in patients following a Traumatic
Brain Injury (TBI). The primary focus was to determine differences in perceptions
between qualified (N = 40) and direct care staff (N = 47). Vignettes depicting
ISB displayed by a male following a TBI were rated. The vignettes varied in
behaviour (intimate versus non-contact) and age of the victim (child versus
adult). Ratings for causal explanations (poor management, attention seeking,
negative emotion and education), attributions (need for action and increase
awareness) and emotions were analysed alongside risk assessment and management
variables. Intimate contact ISB and ISB directed towards a child were perceived
to be more serious and in need of intervention. Direct care staff perceived ISB
to be due to sexual motivations, poor emotion control and to seek attention. They
elicited greater negative emotions and based their judgements of risk on
seriousness. On the other hand, qualified staff were more concerned about
implementing interventions based on the risk of recurrence. Differences between
staff groups could cause conflict regarding the assessment and management of ISB
in TBI. Training to increase awareness of the behaviour could minimise
differences and produce greater cohesion within clinical practise.
PMID- 29936907
TI - Hot hands, cold feet? Investigating effects of interacting constraints on place
kicking performance at the 2015 Rugby Union World Cup.
AB - Place kicks in Rugby Union present valuable opportunities to score points outside
the spatiotemporal dynamics of open play but are executed under varying
performance constraints. We analysed effects of specific task constraints and
relevant contextual factors on place kick performance in the 2015 Rugby Union
World Cup. Data were collected from television broadcasts for each place kick. In
addition to kick outcomes, contextual factors, including time of the kick in the
match, score margin at the time of the kick, and outcome of the kicker's previous
kick, were recorded. Effects of spatial task constraints were analysed for each
kick, using distance (m) and angle ( degrees ) of the kick to the goalposts. A
binomial logistic regression model revealed that distance from, and angle to, the
goalposts were significant predictors of place kick outcome. Furthermore, the
success percentage of kickers who missed their previous kick was 7% lower than
those who scored their previous kick. Place kick success percentage in the 10
minutes before half-time was 8% lower than the mean tournament success
percentage, which was 75% (95% CI 71-78%). The highest kick success percentage
was recorded when scores were level (83%; 95% CI 72-91%). Our data highlighted
how subtle changes in task constraints and contextual factors can influence
performance outcomes in elite performers in international competition.
Fluctuations in place kick success suggested that individual constraints, such as
thoughts, emotions and fatigue, induced during competition, could interact with
perceptions to influence emergent performance behaviours.
PMID- 29936908
TI - Utility of a minimal skin incision laparotomy technique for removing uterine
leiomyomas at a regional core hospital: a retrospective study.
AB - BACKGROUND: We present a minimal skin wound abdominal myomectomy performed in our
hospital and attempt to identify the optimal range of this technique by
considering the characteristics of target leiomyomas. In this procedure, we
attempted to make the skin wound as small as possible, with a maximum length of
approximately 5 cm. METHODS: In addition to introducing the minimal skin wound
abdominal myomectomy, we retrospectively collected and analyzed the medical
records of 76 patients treated with minimal skin wound abdominal myomectomy
exclusively by the same physician at Maruyama Memorial General Hospital between
January 2007 and December 2016. We statistically investigated relationships
between ten factors, including body mass index; patient's age; patient's parity;
administration of gonadotropin-releasing hormone analogue; presence of anemia;
the uterine leiomyomas' number, size, weight, and location; operation time; and
blood loss. RESULTS: First, we introduce a case in which we performed minimal
skin wound abdominal myomectomy for a 36-year-old Japanese patient with a large
leiomyoma (10 cm in diameter). Then, we assessed the impacts of patient
characteristics and leiomyoma characteristics on operation time and blood loss
for this surgical method. In a multivariate analysis, only the number of resected
leiomyomas significantly affected massive bleeding. Other factors showed no
difference on operation time and the amount of blood loss. CONCLUSIONS: Minimal
skin wound abdominal myomectomy is safe and effective for use in many patients,
because only the number of leiomyomas affects the amount of blood loss. No other
factor affected operation time. We suggest the possibility that the expanded use
of minimal skin wound abdominal myomectomy may reduce the number of patients
waiting for long periods to undergo laparoscopic surgery and may optimize the use
of medical resources in rural areas.
PMID- 29936909
TI - The socioeconomic profile of alcohol-attributable mortality in South Africa: a
modelling study.
AB - BACKGROUND: Globally, illness and life expectancy follow a social gradient that
puts people of lower socioeconomic status (SES) at higher risk of dying
prematurely. Alcohol consumption has been shown to be a factor contributing to
socioeconomic differences in mortality. However, little evidence is available
from low- and middle-income countries. The objective of this study was to
quantify mortality attributable to alcohol consumption in the adult (15+ years)
general population of South Africa in 2015 by SES, age, and sex. METHODS: A
comparative risk assessment was performed using individual and aggregate data
from South Africa and risk relations reported in the literature. Alcohol
attributable fractions (AAFs) and alcohol-attributable mortality rates were
estimated for cause-specific mortality by SES, sex, and age. Monte Carlo
simulation techniques were used to calculate 95% uncertainty intervals (UI).
RESULTS: Overall, approximately 62,300 (95% UI 27,000-103,000) adults died from
alcohol-attributable causes in South Africa in 2015, with 60% of deaths occurring
in people in the low and 15% in the high SES groups. Age-standardized, alcohol
attributable mortality rates per 100,000 adults were highest for the low SES
group (727 deaths, 95% UI 354-1208 deaths) followed by the middle (377 deaths,
95% UI 165-687 deaths) and high SES groups (163 deaths, 95% UI 71-289 deaths).
The socioeconomic differences were highest for mortality from infectious
diseases. People of low SES had a lower prevalence of current alcohol use but
heavier drinking patterns among current drinkers. Among men, AAFs were elevated
at low and middle SES, particularly for the middle and higher age groups (35+).
Among women, AAFs differed less across SES groups and, in the youngest age group
(15-34), women of high SES had elevated AAFs. CONCLUSIONS: Alcohol use
contributed to vast socioeconomic differences in mortality. Where observed,
elevated AAFs for people of low and middle SES arose from higher levels of
consumption among current drinkers and not from the prevalence of current alcohol
use per se. The findings can direct preventive measures and interventions on
those at highest risk. Future research is needed to investigate socioeconomic
differences in the risk functions relating alcohol use to cause-specific
mortality.
PMID- 29936910
TI - Cardiovascular magnetic resonance black-blood thrombus imaging for the diagnosis
of acute deep vein thrombosis at 1.5 Tesla.
AB - BACKGROUND: The aim was to investigate the feasibility of a cardiovascular
magnetic resonance (CMR) black-blood thrombus imaging (BBTI) technique, based on
delay alternating with nutation for tailored excitation black-blood preparation
and a variable flip angle turbo-spin-echo readout, for the diagnosis of acute
deep vein thrombosis (DVT) at 1.5 T. METHODS: BBTI was conducted in 15 healthy
subjects and 30 acute DVT patients. Contrast-enhanced CMR venography (CE-CMRV)
was conducted for comparison and only performed in the patients. Apparent
contrast-to-noise ratios between the thrombus and the muscle/lumen were
calculated to determine whether BBTI could provide an adequate thrombus signal
for diagnosis. Two blinded readers assessed the randomized BBTI images from all
participants and made independent decisions on the presence or absence of
thrombus at the segment level. Images obtained by CE-CMRV were also randomized
and assessed by the two readers. Using the consensus CE-CMRV as a reference, the
sensitivity, specificity, positive and negative predictive values, and accuracy
of BBTI, as well as its diagnostic agreement with CE-CMRV, were calculated.
Additionally, diagnostic confidence and interobserver diagnostic agreement were
evaluated. RESULTS: The thrombi in the acute phase exhibited iso- or hyperintense
signals on the BBTI images. All the healthy subjects were correctly identified
from the participants based on the segment level. The diagnostic confidence of
BBTI was comparable to that of CE-CMRV (3.69 +/- 0.52 vs. 3.70 +/- 0.47). High
overall sensitivity (95.2%), SP (98.6%), positive predictive value (96.0%),
negative predictive value (98.3%), and accuracy (97.7%), as well as excellent
diagnostic and interobserver agreements, were achieved using BBTI. CONCLUSION:
BBTI is a reliable, contrast-free technique for the diagnosis of acute DVT at 1.5
T.
PMID- 29936911
TI - The tip of the iceberg: postpartum suicidality in Israel.
AB - BACKGROUND: Postpartum suicidality, a result of extreme distress or depression,
is a tragedy for the woman, infant, and family. Screening for postpartum
depression (PPD) is mandatory in Israel, including a question on suicidal
ideation. This study presents and analyzes data regarding rates, trends and
characteristics of postpartum women who considered, attempted, or completed
suicide, to help direct services aimed at preventing these occurrences. METHODS:
Suicidal ideation data based on PPD screening was drawn from various publications
and databases. Suicide attempt data was obtained from the Emergency Department
database for 2006-2015 and matched with the National Birth Registry. Cause of
death from the national database for those years were similarly linked to births
to identify postpartum suicides and deaths. Postpartum and non-postpartum suicide
attempt rates were computed by year, and by age and ethnic/immigrant group. A
multivariate logistic model was used to estimate relative risk for postpartum
attempts, controlling for age and ethnic group. RESULTS: Suicidal ideation in
recent years has been reported as 1% or less, with higher rates found in studies
of Arab women. Suicide attempt rates for non-postpartum women were 3-5 times that
of postpartum women, rising over the years, while remaining relatively stable for
postpartum women. Adjusted risk of suicide attempt for non-postpartum women was
significantly higher; adjusted odds ratio was 4.08 (95% CI 3.75-4.44). It was
also significantly higher for Arabs and immigrants from the Former Soviet Union,
compared to Israeli-born Jews/veteran immigrants, and for younger women compared
to those aged 35-44. Seven postpartum suicides were recorded during 2006-2015, a
rate of 0.43 per 100,000 births. CONCLUSION: Postpartum suicidality in Israel is
low relative to other countries. Although relatively rare and lower than among
non-postpartum women, health professionals should be attentive to risk factors,
such as past psychiatric disorders, suicide attempts and current emotional
distress, particularly among higher-risk populations. The universal screening
program for PPD is a valuable opportunity for this, but increased resources
should be allotted to implement and utilize it optimally. Prenatal screening
should be added as an Israeli Quality Indicator, and postpartum completed
suicides should be thoroughly investigated to guide prevention efforts.
PMID- 29936912
TI - Exposure to environmental tobacco smoke in non - smoking adults in Israel:
results of the second Israel biomonitoring survey.
AB - BACKGROUND: Exposure to environmental tobacco smoke (ETS) increases the risk of
heart and respiratory disease, cancer, and premature mortality in non-smoking
individuals. Results from the first Israel Biomonitoring Study in 2011 showed
that over 60% of non-smoking adults are exposed to ETS. The purpose of the
current study was to assess whether policies to restrict smoking in public places
have been associated with reductions in exposure to ETS, and to examine
predictors of exposure. METHODS: We analyzed urinary cotinine and creatinine
concentrations in 194 adult participants in the National Health and Nutrition
(RAV MABAT) Survey in 2015-2016. Study participants were interviewed in person on
smoking status and exposure to ETS. We calculated creatinine-adjusted and
unadjusted urinary cotinine geometric means and medians among smokers and non
smokers. We analyzed associations in univariable analyses, between socio
demographic variables and self - reported exposure, and urinary cotinine
concentrations. RESULTS: There was no reduction in geometric mean urinary
cotinine levels in non-smokers in the current study (1.7 MUg/g) compared to that
in 2011 (1.6 MUg/g). Median cotinine levels among the non - smoking Arab
participants were higher in comparison to the Jewish and other participants (2.97
versus 1.56 MUg/l, p = 0.035). Participants who reported that they were exposed
to ETS at home had significantly higher median levels of creatinine adjusted
urinary cotinine than those reporting they were not exposed at home (4.19 MUg/g
versus 2.9 MUg/g, p = 0.0039). CONCLUSIONS: Despite additional restrictions on
smoking in public places in 2012-2016, over 60% of non-smoking adults in Israel
continue to be exposed to ETS. Urinary cotinine levels in non-smokers have not
decreased compared to 2011. Results indicate higher exposure to ETS in Arab study
participants and those reporting ETS exposure at home. There is an urgent need:
(1) to increase enforcement on the ban on smoking in work and public places; (2)
for public health educational programs and campaigns about the adverse health
effects of ETS; and (3) to develop and disseminate effective interventions to
promote smoke free homes. Periodic surveys using objective measures of ETS
exposure (cotinine) are an important tool for monitoring progress, or lack
thereof, of policies to reduce exposure to tobacco smoke in non-smokers.
PMID- 29936913
TI - Osteolytic lesions (brown tumors) of primary hyperparathyroidism misdiagnosed as
multifocal giant cell tumor of the distal ulna and radius: a case report.
AB - BACKGROUND: Brown tumors represent a rare clinical manifestation reported in
approximately 3% of patients with primary hyperparathyroidism and correspond to
radiologically osteolytic lesions with well-defined borders in different parts of
the skeleton. CASE PRESENTATION: We report the case of a 53-year-old white man
who presented to our hospital with osteolytic lesions of his distal ulna and
radius, causing pain and swelling of 2-month duration. A subsequent biopsy
revealed histological features consistent with giant cell tumor and a complete
resection of his distal ulna was followed, along with curettage and cementoplasty
of the distal radial metaphysis. Two weeks later, he was re-admitted with diffuse
musculoskeletal soreness, anorexia, constipation, nausea, and localized abdominal
pain and multiple osteolytic lesions on plain radiographs. A histopathological
examination of the ulna and radius specimens showed similar findings and, given
the multifocality, brown tumors related to primary or secondary
hyperparathyroidism was included in the differential diagnosis. A laboratory
examination showed high total serum calcium (14.5 mg/dl) and low serum phosphorus
and 25-hydroxyvitamin D levels. Primary hyperparathyroidism was suspected and
confirmed by the elevated parathyroid hormone levels of 1453 pg/mL. At
radiological work-up, using computed tomography, ultrasonography, and parathyroid
subtraction technetium-99m sestamibi scintigraphy, a 4.5 * 2.5 * 3.2 cm mass
emanating from the right lobe of his thyroid gland was detected, displaying
extensive uptake in the right lower parathyroid gland. After appropriate medical
support including hyperhydration and high doses of diuretics and diphosphonates,
his laboratory profile normalized and he underwent total thyroidectomy with
removal of the parathyroid glands. Our patient is now recovering 12 months after
surgery, with normal values of serum parathyroid hormone and calcium levels. The
lytic bone lesions have almost disappeared and no other additional orthopedic
intervention was necessary. CONCLUSIONS: The present case report emphasizes the
need of inclusion of brown tumors in the differential diagnosis of multifocal
osteolytic bone lesions, in order to avoid harmful surgical interventions.
Laboratory testing of serum phosphate, calcium levels, and parathyroid hormone
levels should always be included in the routine survey of patients with
multifocal osteolytic lesions.
PMID- 29936915
TI - Long-Term Cognitive Outcomes in Patients with Autoimmune Encephalitis.
AB - BACKGROUND: A need exists to characterise the long-term cognitive outcomes in
patients who recovered from autoimmune encephalitis and to identify the
modifiable factors associated with improved outcomes. METHODS: We retrospectively
analysed data from patients diagnosed with autoimmune encephalitis in our
outpatient autoimmune encephalitis clinic over a 5-year period, where the
Montreal Cognitive Assessment (MoCA) is routinely administered. RESULTS: In
total, 21 patients met the inclusion criteria, of whom 52% had persistent
cognitive impairment at their latest follow-up (median delay to testing=20
months, range 13-182). Visuospatial and executive abilities, language, attention,
and delayed recall were predominantly affected. Patients with status epilepticus
at presentation had lower total MoCA scores at their last follow-up (median total
score 21, range 15-29) compared with patients without status epilepticus at
presentation (median total score 27.5, range 21-30; r 2=0.366, p=0.004). Patients
who experienced delays of more than 60 days from symptom onset to initiation of
treatment (either immunosuppression or tumour removal) were more likely to have a
MoCA score compatible with cognitive impairment at their last follow-up (r
2=0.253, p=0.0239; z-score=-2.01, p=0.044). CONCLUSIONS: Our study suggests that
the MoCA may be used to evaluate cognition in recovering patients with autoimmune
encephalitis. Delays to treatment shorter than 60 days and absence of status
epilepticus at onset were associated with better performance on the MoCA obtained
more than 1 year after symptom onset, and may predict better long-term cognitive
outcomes.
PMID- 29936914
TI - A North American stem turaco, and the complex biogeographic history of modern
birds.
AB - BACKGROUND: Earth's lower latitudes boast the majority of extant avian species
level and higher-order diversity, with many deeply diverging clades restricted to
vestiges of Gondwana. However, palaeontological analyses reveal that many avian
crown clades with restricted extant distributions had stem group relatives in
very different parts of the world. RESULTS: Our phylogenetic analyses support the
enigmatic fossil bird Foro panarium Olson 1992 from the early Eocene (Wasatchian)
of Wyoming as a stem turaco (Neornithes: Pan-Musophagidae), a clade that is
presently endemic to sub-Saharan Africa. Our analyses offer the first well
supported evidence for a stem musophagid (and therefore a useful fossil
calibration for avian molecular divergence analyses), and reveal surprising new
information on the early morphology and biogeography of this clade. Total-clade
Musophagidae is identified as a potential participant in dispersal via the
recently proposed 'North American Gateway' during the Palaeogene, and new
biogeographic analyses illustrate the importance of the fossil record in
revealing the complex historical biogeography of crown birds across geological
timescales. CONCLUSIONS: In the Palaeogene, total-clade Musophagidae was
distributed well outside the range of crown Musophagidae in the present day. This
observation is consistent with similar biogeographic observations for numerous
other modern bird clades, illustrating shortcomings of historical biogeographic
analyses that do not incorporate information from the avian fossil record.
PMID- 29936916
TI - Vitamin D supplement use and associated demographic, dietary and lifestyle
factors in 8024 South Asians aged 40-69 years: analysis of the UK Biobank cohort.
AB - OBJECTIVE: Vitamin D deficiency (serum 25-hydroxyvitamin D60 years: OR=0.75; 95 %
CI 0.65, 0.86) and in those living outside Greater London (OR=0.53 to 0.77), with
borderline trends for a lower BMI, higher oily fish intake and higher household
income associated with increased odds of vitamin D supplement use. CONCLUSIONS:
Vitamin D supplements were not used by most South Asians and intakes from diet
alone are likely to be insufficient to maintain adequate vitamin D status. Public
health strategies are now urgently required to promote the use of vitamin D
supplements in these specific UK South Asian subgroups.
PMID- 29936917
TI - Cognitive deterioration in schizophrenia: aging and cerebrovascular disease.
AB - Today, cognitive dysfunction is accepted as a feature of schizophrenia. As the
patients age, this dysfunction is higher and harder to evaluate due to the
interaction among aging, other somatic diseases, psychoactive drugs, etc.
PMID- 29936918
TI - Vitamin D supplementation and inflammatory and metabolic biomarkers in patients
with knee osteoarthritis: post hoc analysis of a randomised controlled trial.
AB - The aim of this study was to determine whether vitamin D supplementation and
maintaining vitamin D sufficiency are associated with changes in inflammatory and
metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D
deficiency. A total of 413 participants with symptomatic knee OA and vitamin D
deficiency were enrolled in a randomised, placebo-controlled trial and received
1.25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this
post hoc analysis, 200 participants from one site (ninety-four from the placebo
group and 106 from the vitamin D group; mean age 63.1 (sd 7.3) years, 53.3 %
women) were randomly selected for measurement of serum levels of inflammatory and
metabolic biomarkers at baseline and 24 months using immunoassays. In addition,
participants were classified into two groups according to serum 25-hydroxyvitamin
D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient
(25(OH)D<=50 nmol/l at either month 3 or 24, n 61), and (2) consistently
sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with
placebo, vitamin D supplementation had no significant effect on change in serum
high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin,
resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2
years was also not associated with changes in these biomarkers compared with not
being consistently sufficient. Vitamin D supplementation and maintaining vitamin
D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers
over 2 years in knee OA patients who were vitamin D insufficient, suggesting that
they may not affect systemic inflammation in knee OA patients.
PMID- 29936919
TI - Invited commentary in response to: selenium supplementation lowers insulin
resistance and markers of cardio-metabolic risk in patients with congestive heart
failure: a randomised, double-blind, placebo-controlled trial.
PMID- 29936920
TI - The tissue profile of metabolically active coenzyme forms of vitamin B12 differs
in vitamin B12-depleted rats treated with hydroxo-B12 or cyano-B12.
AB - Recent rat studies show different tissue distributions of vitamin B12 (B12),
administered orally as hydroxo-B12 (HO-B12) (predominant in food) and cyano-B12
(CN-B12) (common in supplements). Here we examine male Wistar rats kept on a low
B12 diet for 4 weeks followed by a 2-week period on diets with HO-B12 (n 9) or CN
B12 (n 9), or maintained on a low-B12 diet (n 9). Plasma B12 was analysed before,
during and after the study. The content of B12 and its variants (HO-B12,
glutathionyl-B12, CN-B12, 5'-deoxyadenosyl-B12 (ADO-B12), and methyl-B12 (CH3
B12)) were assessed in the tissues at the end of the study. A period of 4 weeks
on the low-B12 diet reduced plasma B12 by 58 % (from median 1323 (range 602-1791)
to 562 (range 267-865) pmol/l, n 27). After 2 weeks on a high-B12 diet (week 6 v.
week 4), plasma B12 increased by 68 % (HO-B12) and 131 % (CN-B12). Total B12 in
the tissues accumulated differently: HO-B12>CN-B12 (liver, spleen), HO-B12=50
years) from the Irish Longitudinal Study on Ageing (TILDA) (Wave 1) are presented
here. Measures included plasma total vitamin B12 and folate, whereas predictors
included detailed demographic, socio-economic, geographic, seasonal and
health/lifestyle data. The prevalence of deficient or low B12 status (45 nmol/l)
was observed in 8.9 %, whereas high B12 status was observed in 3.1 % (>601
pmol/l). The largest positive predictor of B12 concentration was self-reported
B12 injection and/or supplement use (coefficient 51.5 pmol/; 95 % CI 9.4, 93.6;
P=0.016) followed by sex and geographic location. The largest negative predictor
was metformin use (-33.6; 95 % CI -51.9, -15.4; P<0.0001). The largest positive
predictor of folate concentration was folic acid supplement use (6.0; 95 % CI
3.0, 9.0 nmol/l; P<0.001) followed by being female and statin medications. The
largest negative predictor was geographic location (-5.7; 95 % CI -6.7, -4.6;
P<0.0001) followed by seasonality and smoking. B-vitamin status in older adults
is affected by health and lifestyle, medication, sampling period and geographic
location. We observed a high prevalence of low B12 and folate status, indicating
that the current policy of voluntary fortification is ineffective for older
adults.
PMID- 29936927
TI - Adherence to the healthy Nordic diet is associated with weight change during 7
years of follow-up.
AB - Studies indicate that the healthy Nordic diet may improve heart health, but its
relation to weight change is less clear. We studied the association between the
adherence to the healthy Nordic diet and long-term changes in weight, BMI and
waist circumference. Furthermore, the agreement between self-reported and
measured body anthropometrics was examined. The population-based DIetary,
Lifestyle and Genetic Determinants of Obesity and Metabolic syndrome Study in
2007 included 5024 Finns aged 25-75 years. The follow-up was conducted in 2014 (n
3735). One-third of the participants were invited to a health examination. The
rest were sent measuring tape and written instructions along with questionnaires.
The Baltic Sea Diet Score (BSDS) was used to measure adherence to the healthy
Nordic diet. Association of the baseline BSDS and changes in BSDS during the
follow-up with changes in body anthropometrics were examined using linear
regression analysis. The agreement between self-reported and nurse-measured
anthropometrics was determined with Bland-Altman analysis. Intra-class
correlation coefficients between self-reported and nurse-measured anthropometrics
exceeded 0.95. The baseline BSDS associated with lower weight (beta=-0.056,
P=0.043) and BMI (beta=-0.021, P=0.031) over the follow-up. This association was
especially evident among those who had increased their BSDS. In conclusion, both
high initial and improved adherence to the healthy Nordic diet may promote long
term weight maintenance. The self-reported/measured anthropometrics were shown to
have high agreement with nurse-measured values which adds the credibility of our
results.
PMID- 29936928
TI - Effects of environmental temperature and dietary zinc on egg production
performance, egg quality and antioxidant status and expression of heat-shock
proteins in tissues of broiler breeders.
AB - To investigate the effects of environmental temperature and dietary Zn on egg
production performance, egg quality and antioxidant status, as well as expression
of heat-shock proteins (HSP) in tissues, of laying broiler breeders, we used a
completely randomised design with a 2*3 factorial arrangement of treatments. The
two environmental temperatures were normal (21+/-1 degrees C, NT) and high (32+/
1 degrees C, HT). The three dietary Zn sources were a Zn-unsupplemented basal
diet (CON), and the basal diet supplemented with 110 mg Zn/kg as either the
inorganic Zn sulphate (iZn) or the organic Zn proteinate with a moderate
chelation strength (oZn). HT decreased (P<0.002) egg weight, laying rate,
eggshell strength, thickness and weight, but increased (P<=0.05) rectal
temperature, broken egg rate, misshapen egg rate, feed:egg ratio, Cu Zn
superoxide dismutase activities in liver and pancreas, as well as metallothionein
(MT) level in pancreas, and HSP70 mRNA levels in liver and pancreas of laying
broiler breeders. Broiler breeders fed the oZn diet had higher (P<0.04) Zn
content in the liver, as well as MT levels in the liver and pancreas, compared
with those fed the CON diet. Under HT, broiler breeders fed the oZn diet had
higher (P<0.05) Zn content in the pancreas compared with those fed the iZn and
CON diets. The results from this study indicated that HT impaired egg production
performance and eggshell quality possibly because of the disturbed redox balance
and HSP homoeostasis, whereas the oZn is more available than the iZn for
pancreatic Zn of heat-stressed laying broiler breeders.
PMID- 29936929
TI - TRRAP stimulates the tumorigenic potential of ovarian cancer stem cells.
AB - Ovarian cancer is the most fatal gynecological malignancy in women and
identification of new therapeutic targets is essential for the continued
development of therapy for ovarian cancer. TRRAP (transformation/transcription
domain-associated protein) is an adaptor protein and a component of histone
acetyltransferase complex. The present study was undertaken to investigate the
roles played by TRRAP in the proliferation and tumorigenicity of ovarian cancer
stem cells. TRRAP expression was found to be up-regulated in the sphere cultures
of A2780 ovarian cancer cells. Knockdown of TRRAP significantly decreased cell
proliferation and the number of A2780 spheroids. In addition, TRRAP knockdown
induced cell cycle arrest and increased apoptotic percentages of A2780 sphere
cells. Notably, the mRNA levels of stemness-associated markers, that is, OCT4,
SOX2, and NANOG, were suppressed in TRRAP-silenced A2780 sphere cells. In
addition, TRRAP overexpression increased the mRNA level of NANOG and the
transcriptional activity of NANOG promoter in these cells. Furthermore, TRRAP
knockdown significantly reduced tumor growth in a murine xenograft
transplantation model. Taken together, the findings of the present study suggest
that TRRAP plays an important role in the regulation of the proliferation and
stemness of ovarian cancer stem cells. [BMB Reports 2018; 51(10): 515-520].
PMID- 29936930
TI - Genomic characterization of clonal evolution during oropharyngeal carcinogenesis
driven by human papillomavirus 16.
AB - Secondary prevention via earlier detection would afford the greatest chance for a
cure in premalignant lesions. We investigated the exomic profiles of non
malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC)
and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in
oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome
(WGS) sequencing were performed on peripheral blood and adjacent non-tumor and
tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next
generation sequencing yielded an average coverage of 94.3* for WES and 35.3* for
WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were
unable to identify common cancer-associated early mutations and copy number
alterations (CNA) except in one pair. Interestingly, in this case, we observed
that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal
under a microscope; however, this tissue also showed weak p16 expression. WGS
revealed the infection and integration of high-risk type HPV16 in this tissue as
well as in the matched tumor. Furthermore, WES identified shared and tumor
specific genomic alterations for this pair. Clonal analysis enabled us to infer
the process by which this transitional crypt epithelium (TrCE) evolved into a
tumor; this evolution was accompanied by the subsequent accumulation of genomic
alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter
amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis
is a stepwise evolutionary process that is consistent with a multistep
carcinogenesis model. Our results highlight the carcinogenic changes driven by
HPV16 infection and provide a basis for the secondary prevention of OPSCC. [BMB
Reports 2018; 51(11): 584-589].
PMID- 29936931
TI - LJ-1888, a selective antagonist for the A3 adenosine receptor, ameliorates the
development of atherosclerosis and hypercholesterolemia in apolipoprotein E knock
out mice.
AB - Cardiovascular diseases arising from atherosclerosis are the leading causes of
mortality and morbidity worldwide. Lipid-lowering agents have been developed in
order to treat hypercholesterolemia, a major risk factor for atherosclerosis.
However, the prevalence of cardiovascular diseases is increasing, indicating a
need to identify novel therapeutic targets and develop new treatment agents.
Adenosine receptors (ARs) are emerging as therapeutic targets in asthma,
rheumatoid arthritis, cancer, ischemia, and inflammatory diseases. This study
assessed whether LJ-1888, a selective antagonist for A3 AR, can inhibit the
development of atherosclerosis in apolipoprotein E knock-out (ApoE-/-) mice who
are fed a western diet. Plaque formation was significantly lower in ApoE-/- mice
administered LJ-1888 than in mice not administered LJ-1888, without any
associated liver damage. LJ-1888 treatment of ApoE-/- mice prevented western diet
induced hypercholesterolemia by markedly reducing low-density lipoprotein
cholesterol levels and significantly increasing high-density lipoprotein
cholesterol concentrations. Reduced hypercholesterolemia in ApoE-/- mice
administered LJ-1888 was associated with the enhanced expression of genes
involved in bile acid biosynthesis. These findings indicate that LJ-1888, a
selective antagonist for A3 AR, may be a novel candidate for the treatment of
atherosclerosis and hypercholesterolemia. [BMB Reports 2018; 51(10): 521-526].
PMID- 29936933
TI - Telomere association of Oryza sativa telomere repeat-binding factor like 1 and
its roles in telomere maintenance and development in rice, Oryza sativa L.
AB - Telomeres are specialized nucleoprotein complexes that function to protect
eukaryotic chromosomes from recombination and erosion. Several telomere binding
proteins (TBPs) have been characterized in higher plants, but their detailed in
vivo functions at the plant level are largely unknown. In this study, we
identified and characterized OsTRFL1 (Oryza sativa Telomere Repeat-binding Factor
Like 1) in rice, a monocot model crop. Although OsTRFL1 did not directly bind to
telomere repeats (TTTAGGG)4 in vitro, it was associated with telomeric sequences
in planta. OsTRFL1 interacted with rice TBPs, such as OsTRBF1 and RTBP1, in yeast
and plant cells as well as in vitro. Thus, it seems likely that the association
of OsTRFL1 with other TBPs enables OsTRFL1 to bind to telomeres indirectly. T-DNA
inserted OsTRFL1 knock-out mutant rice plants displayed significantly longer
telomeres (6-25 kb) than those (5-12 kb) in wild-type plants, indicating that
OsTRFL1 is a negative factor for telomere lengthening. The reduced levels of
OsTRFL1 caused serious developmental defects in both vegetative and reproductive
organs of rice plants. These results suggest that OsTRFL1 is an essential factor
for the proper maintenance of telomeres and normal development of rice. [BMB
Reports 2018; 51(11): 578-583].
PMID- 29936932
TI - Protective effects of Tat-DJ-1 protein against streptozotocin-induced diabetes in
a mice model.
AB - A major feature of type 1 diabetes mellitus (T1DM) is hyperglycemia and
dysfunction of pancreatic beta-cells. In a previous study, we have shown that Tat
DJ-1 protein inhibits pancreatic RINm5F beta-cell death caused by oxidative
stress. In this study, we examined effects of Tat-DJ-1 protein on streptozotocin
(STZ)-induced diabetic mice. Wild type (WT) Tat-DJ-1 protein transduced into
pancreas where it markedly inhibited pancreatic beta-cell destruction and
regulated levels of serum parameters including insulin, alkaline phosphatase
(ALP), and free fatty acid (FFA) secretion. In addition, transduced WT Tat-DJ-1
protein significantly inhibited the activation of NF-kappaB and MAPK (ERK and
p38) expression as well as expression of COX-2 and iNOS in STZ exposed pancreas.
In contrast, treatment with C106A mutant Tat-DJ-1 protein showed no protective
effects. Collectively, our results indicate that WT Tat-DJ-1 protein can
significantly ameliorate pancreatic tissues in STZ-induced diabetes in mice. [BMB
Reports 2018; 51(7): 362-367].
PMID- 29936934
TI - Nitric oxide activation by progesterone suppresses ATP-induced ciliary activity
in oviductal ciliated cells.
AB - Ciliary beat frequency (CBF) regulates the oviductal transport of oocytes and
embryos, which are important components of the reproductive process. Local
release of ATP transiently increases CBF by increasing [Ca2+]i. Ovarian hormones
also regulate ciliary activity and oviductal transport. Progesterone (P4) induces
nitric oxide (NO) production and high P4 concentrations induce ciliary
dysfunction. However, the mechanism by which P4 affects CBF has not been
elucidated. To evaluate the role of P4 in NO production and its effect on ATP
induced increases in CBF, we measured CBF, NO concentrations and [Ca2+]i in
cultures of oviductal ciliated cells treated with P4 or NO signalling-related
molecules. ATP induced a [Ca2+]i peak, followed by an increase in NO
concentrations that were temporally correlated with the decreased phase of the
transiently increased CBF. Furthermore, P4 increased the expression of nitric
oxide synthases (iNOS and nNOS) and reduced the ATP-induced increase in CBF via a
mechanism that involves the NO signalling pathway. These results have improved
our knowledge about intracellular messengers controlling CBF and showed that NO
attenuates oviduct cell functions. Furthermore, we showed that P4 regulates
neurotransmitter (ATP) actions on CBF via the NO pathway, which could explain
pathologies where oviductal transport is altered and fertility decreased.
PMID- 29936943
TI - Dual-Energy Computed Tomography: Technology and Challenges.
AB - Dual-energy computed tomography (CT) is an imaging technique in which the same
axial slice of the patient is scanned with two different X-ray spectra in order
to extract chemical information or improve diagnostic image quality. This method
is useful for the detection or visualization of heavy atoms like iodine but the
differentiation of soft tissue types containing only light atoms is usually not
markedly improved compared with single-energy CT. The commercially available dual
energy CT scanners use different technological approaches that differ in
complexity and result quality.
PMID- 29936944
TI - Dual-Energy Computed Tomography: Image Acquisition, Processing, and Workflow.
AB - Dual energy computed tomography has been available for more than 10 years;
however, it is currently on the cusp of widespread clinical use. The way dual
energy data are acquired and assembled must be appreciated at the clinical level
so that the various reconstruction types can extend its diagnostic power. The
type of scanner that is present in a given practice dictates the way in which the
dual energy data can be presented and used. This article compares and contrasts
how dual source, rapid kV switching, and spectral technologies acquire and
present dual energy reconstructions to practicing radiologists.
PMID- 29936945
TI - Dual-Energy Computed Tomography in Cardiothoracic Vascular Imaging.
AB - Dual energy computed tomography is becoming increasingly widespread in clinical
practice. It can expand on the traditional density-based data achievable with
single energy computed tomography by adding novel applications to help reach a
more accurate diagnosis. The implementation of this technology in cardiothoracic
vascular imaging allows for improved image contrast, metal artifact reduction,
generation of virtual unenhanced images, virtual calcium subtraction techniques,
cardiac and pulmonary perfusion evaluation, and plaque characterization. The
improved diagnostic performance afforded by dual energy computed tomography is
not associated with an increased radiation dose. This review provides an overview
of dual energy computed tomography cardiothoracic vascular applications.
PMID- 29936946
TI - Role of Dual-Energy Computed Tomography in Thoracic Oncology.
AB - Dual-energy CT (DECT) is an emerging technology that has potential to enhance
diagnostic performance and radiologists' confidence in the evaluation of thoracic
malignancies. DECT clinical applications include characterization of solitary
pulmonary nodule, lung masses and mediastinal tumors. DECT-derived iodine uptake
quantification may assist in characterization of tumor differentiation and gene
expression. The use DECT in oncology has potential to improve lung cancer
staging, therapy planning, and assessment of response to therapy as well as
detection of incidental pulmonary embolism.
PMID- 29936947
TI - Practical Applications of Dual-Energy Computed Tomography in the Acute Abdomen.
AB - With new developments in workflow automation, as well as technological advances
enabling faster imaging with improved image quality and dose profile, dual-energy
computed tomography is being used more often in the imaging of the acutely ill
and injured patient. Its ability to identify iodine, differentiate it from
hematoma or calcification, and improve contrast resolution has proven invaluable
in the assessment of organ perfusion, organ injury, and inflammation.
PMID- 29936948
TI - The Role of Dual-Energy Computed Tomography in Assessment of Abdominal Oncology
and Beyond.
AB - The added value and strength of dual energy computed tomography for the
evaluation of oncologic patients revolve around the use of lower energy
reconstructed images and iodine material density images. Lower keV simulated
monoenergetic images optimize soft tissue tumor to nontumoral attenuation
differences and increase contrast to noise ratios to improve lesion detection.
Iodine material density images or maps are helpful from a qualitative standpoint
for image interpretation because they result in improved detection and
characterization of tumors and lymph node involvement, and from a quantitative
assessment by enabling interrogation of specific properties of tissues to predict
and assess therapeutic response.
PMID- 29936949
TI - Advanced Musculoskeletal Applications of Dual-Energy Computed Tomography.
AB - Dual-energy CT (DECT) is a rapidly growing tool in musculoskeletal radiology. It
has been validated as an accurate imaging modality for the assessment of gout and
bone marrow edema. DECT can be used to reduce metal artifacts. A few studies have
shown its ability to calculate bone mineral density and examine pathologic states
in tendons and ligaments. Its capacity for material separation suggests its
emergence as a technique for arthrography, and for the evaluation of
intervertebral discs and other inflammatory arthropathies.
PMID- 29936950
TI - Dual-Energy Computed Tomography: Dose Reduction, Series Reduction, and Contrast
Load Reduction in Dual-Energy Computed Tomography.
AB - Evolution in computed tomography technology and image reconstruction have
significantly changed practice. Dual energy computed tomography is being
increasingly adopted owing to benefits of material separation, quantification,
and improved contrast-to-noise ratio. The radiation dose can match that from
single energy computed tomography. Spectral information derived from a
polychromatic x-ray beam at different energies yields in image reconstructions
that reduce the number of phases in a multiphasic examination and decrease the
absolute amount of contrast media. This increased analytical and image processing
capability provides new avenues for addressing radiation dose and iodine exposure
concerns.
PMID- 29936951
TI - Pearls, Pitfalls, and Problems in Dual-Energy Computed Tomography Imaging of the
Body.
AB - Dual-energy computed tomography (DECT) is an exciting technology that is
increasing in routine use and has the potential for significant clinical impact.
With the advancement of DECT, it is important for radiologists to be aware of
potential challenges with DECT acquisition and postprocessing, and to have a
basic knowledge of unique artifacts and diagnostic pitfalls that can occur when
interpreting DECT scans and DECT postprocessed images. This article serves as a
practical overview of potential problems and diagnostic pitfalls associated with
DECT, and steps that can be taken to avoid them.
PMID- 29936952
TI - Strategies to Improve Image Quality on Dual-Energy Computed Tomography.
AB - Dual-energy computed tomography (DECT) offers several advantages over
conventional single-energy CT. These advantages include improved image quality,
beam hardening correction, and metal artifact reduction. Additionally, DECT
allows derivation of quantitative information through material decomposition
analysis. Although newer third-generation rapid-kilovolt switching and dual
source DECT scanners have significantly improved in image quality and workflow
compared with initial iterations and early scanners, sources of potential image
quality degradation can exist secondary to the inherent capabilities in which the
image acquisition occurs.
PMID- 29936954
TI - Multienergy Computed Tomography: A New Horizon in Computed Tomographic Imaging.
PMID- 29936956
TI - You say "to-ma-to," I say "to-mah-to," you say "covariate," I say....
PMID- 29936957
TI - 50 Years Ago in The Journal of Pediatrics: Significance of Leukemia Clusters.
PMID- 29936958
TI - 50 Years Ago in The Journal of Pediatrics: Platelet Counts in Healthy Premature
Infants.
PMID- 29936959
TI - Negative association between obesity and academic performance-Physical fitness
may help mediate the effects.
PMID- 29936960
TI - Dental caries-something to sink your teeth into.
PMID- 29936961
TI - Psychosocial factors and attrition from weight management.
PMID- 29936962
TI - No answers yet for the prevention of neonatal hypoglycemia.
PMID- 29936963
TI - Prenatal superior to postnatal myelomeningocele surgery.
PMID- 29936964
TI - Fluid overload in critically ill children is associated with increased mortality.
PMID- 29936965
TI - Sudden unexpected infant death rates differ by age at death.
PMID- 29936966
TI - Subthreshold phototherapy during birth hospitalization may prevent readmission
for phototherapy.
PMID- 29936967
TI - Corporal punishment associated with dating violence.
PMID- 29936968
TI - Food Insecurity and Children's Rights to Adequate Nutrition in Europe.
PMID- 29936969
TI - Paracetamol for ductal closure: Inching closer, but cautiously!
PMID- 29936970
TI - Cardiac surgery and hearing loss.
PMID- 29936971
TI - Does learning or encouragement influence results for the 6-minute walk test?
PMID- 29936972
TI - The Elephant in the Examination Room: Addressing Parent and Child Mobile Device
Use as a Teachable Moment.
PMID- 29936973
TI - 50 Years Ago in The Journal of Pediatrics: Mefenamic Acid: An Antipyretic for Use
in Children.
PMID- 29936974
TI - Quantification of rib fractures by different scoring systems.
AB - BACKGROUND: The three known systems for evaluation of patients with rib fractures
are rib fracture score (RFS), chest trauma score (CTS), and RibScore (RS). The
aim was to establish critical values for these systems in different patient
populations. METHODS: Retrospective cohort study included 1089 patients with rib
fractures, from level-1 trauma center; divided into two groups: first group
included 620 nongeriatric patients, and second group included 469 geriatric
patients (>=65 y.o.). Additional variables included mortality, injury severity
score (ISS), hospital and intensive care unit lengths of stay (HLOS, ICULOS),
duration of mechanical ventilation, rate of pneumonia (PN), tracheostomy, and
epidural analgesia. RESULTS: RFS critical values were 10 for nongeriatric and
eight for geriatric patients, CTS were four and six respectively, and RS were one
for both. Nongeriatric patients with RFS >=10 versus RFS <10, had higher
mortality, ISS, HLOS, ICULOS, and tracheostomy (P <0.03). Geriatric patients with
RFS >=8 versus RFS <8, had higher mortality, ISS, HLOS, ICULOS, and PN (P <0.03).
Nongeriatric patients with CTS >=4 versus CTS <4, had higher mortality, ISS,
HLOS, ICULOS, duration of mechanical ventilation, and PN (P < 0.02). Geriatric
patients with CTS >=6 versus CTS <6 had greater values for all variables (P <
0.01). Both groups with RS >=1 versus RS <1, had greater values for all variables
(P < 0.05). In geriatric group, prediction of PN was good by CTS (c = 0.8) and
fair by RFS and RS (c = 0.7). CONCLUSIONS: Physicians should choose score to
match specific population and collected variables. RFS is simple but sensitive in
elderly population. CTS is recommended for geriatric patients as it predicts PN
the best. RS is recommended for assessment of severely injured patients with high
ISS.
PMID- 29936975
TI - Impaired growth outcomes in children with congenital colorectal diseases.
AB - BACKGROUND: Cloaca, Hirschsprung disease, and anorectal malformations (CHARM) are
congenital anomalies of the hindgut. Small series have suggested that children
suffering from one of these anomalies may be at risk for growth impairment. We
sought to expand on these findings in a comprehensive cohort, hypothesizing that
patients with Medicaid insurance or African-American (AA) race would be at higher
risk for poor growth. METHODS: Following Institutional Review Board (IRB)
approval, single-institution retrospective review of children with CHARM
anomalies was performed (2009-2016). Body mass index (BMI) value Z-scores were
obtained using the 2006 World Health Organization (age 0-24 mo) and 2000 Centers
for Disease Control (CDC) (age >2 y) growth charts and calculators (statistical
analysis system). Patient factors and BMI Z-scores were analyzed with descriptive
statistics and Fisher's exact test. RESULTS: One hundred sixty-six patients
(Cloaca n = 16, Hirschsprung disease [HD] n = 71, anorectal malformation [ARM] n
= 79) were identified. The BMI Z-score distribution for the entire CHARM cohort
was lower than controls (P < 0.0001). HD and ARM BMI Z-scores were also lower
versus controls (P < 0.0007, P < 0.0037). Requiring more or less than the average
number of surgeries did not impact BMI Z-score [P = non-significant (NS)].
Patients with Medicaid had lower Z-scores versus private or commercial insurance
(P < 0.0001). AA race BMI Z-score distribution was lower than controls (P <
0.0002), but there was no statistical difference in BMI Z-scores when comparing
AA versus non-AA CHARM patients (P = NS). CONCLUSIONS: Patients born with CHARM
anomalies are at risk for impaired growth. Furthermore study is warranted to
identify modifiable risk factors contributing to this impairment. Longitudinal
follow-up should include interventions to mitigate these risks.
PMID- 29936976
TI - H-index and academic rank in general surgery and surgical specialties in the
United States.
AB - BACKGROUND: H-index serves as an alternative to measure academic achievement. Our
objective is to study the h-index as a measure of academic attainment in general
surgery and surgical specialties. METHODS: A database of all surgical programs in
the United States was created. Publish or Perish software was used to determine
surgeons h-index. RESULTS: A total of 134 hospitals and 3712 surgeons (79% male)
were included. Overall, mean h-index was 14.9 +/- 14.8. H-index increased
linearly with academic rank: 6.8 +/- 6.4 for assistant professors (n = 1557,
41.9%), 12.9 +/- 9.3 for associate professors (n = 891, 24%), and 27.9 +/- 17.4
for professors (n = 1170, 31.5%); P < 0.001. Thoracic surgery and surgical
oncology had the highest subspecialty mean h-indices (18.7 +/- 16.7 and 18.4 +/-
17.6, respectively). Surgeons with additional postgraduate degrees, university
affiliations and male had higher mean h-indices; P < 0.001. Scatterplot analysis
showed a strong correlation between h-index and the number of publications (R2 =
0.817) and citations (R2 = 0.768). CONCLUSIONS: The h-index of academic surgeons
correlates with academic rank and serves a potential tool to measure academic
productivity.
PMID- 29936977
TI - Regional diagnostic rates, treatments, and outcomes among patients with invasive
ductal carcinoma.
AB - BACKGROUND: The association between regional breast cancer diagnostic rates,
treatments, and outcomes is unclear. We sought to investigate the management and
survival of women with invasive ductal carcinoma (IDC) from geographic regions
with variable rates of diagnosis. METHODS: Data on women diagnosed with IDC years
2009-2010 were obtained from the Surveillance, Epidemiology, and End Results
database. Patients were divided into quartiles based on the IDC diagnostic rate
within their county of residence. Chi-square and one-way analysis of variance
(ANOVA) analyses tested the association between patient and clinical
characteristics and the diagnostic rate quartiles. Cox regression analyses
compared survival between the quartiles. RESULTS: Among the 83,375 patients
included, the mean age was 60.8 y and 70.9% were white. Patients residing in
counties with the highest diagnostic rates were more frequently white, employed,
educated, and wealthier and more often received adjuvant radiation following both
partial mastectomy for localized disease and complete mastectomy for advanced
disease compared to patients in counties with the lowest diagnostic rates. The
highest diagnostic rate quartile had 10% decreased odds of death compared to the
lower quartile (hazard ratio: 0.897; 95% confidence interval: 0.832-0.966).
However, after adjustment for socioeconomic variables, survival was comparable
(hazard ratio: 0.916; 95% confidence interval: 0.835-1.003). CONCLUSIONS:
Regional variation in IDC diagnostic rates is associated with differences in
socioeconomic status, grade, stage, and treatment. Patients from regions with the
highest rates of diagnosis may have improved access to evidence-based care and
resultant superior survival. Enhancing access to care may improve outcomes of
patients residing in regions where breast cancer is diagnosed less frequently.
PMID- 29936978
TI - How academically productive are endocrine surgeons in the United States?
AB - BACKGROUND: Many surgical departments in the United States lack endocrine surgery
faculty. Although endocrine surgeons can provide worthwhile clinical services, it
is unclear how they contribute to the overall academic mission of the department.
The present study aims to evaluate the academic productivity of endocrine
surgeons, as defined by the American Association of Endocrine Surgeons (AAES)
membership, when compared with other academic surgical faculty. MATERIALS AND
METHODS: An established database of 4081 surgical department faculty was used for
this study. This database includes surgical faculty of the top 50 National
Institutes of Health (NIH) funded universities and faculty from five outstanding
hospital-based surgical departments. Academic metrics including publication,
citations, H-index, and NIH funding were obtained using publically available data
from websites. The AAES membership status was gathered from the online membership
registry. RESULTS: A total of 110 AAES members were identified in this database,
accounting for 2.7% of this population. Overall, the AAES members outperformed
other academic surgical faculty with respect to publications (66 +/- 94 versus 28
+/- 91, P < 0.001), publication citations (1430 +/- 3432 versus 495 +/- 2955, P <
0.001), and H-index (19 +/- 18 versus 10 +/- 13, P < 0.001). In addition, the
AAES members were more likely to have former/current NIH funding and hold
divisional or departmental leadership positions than their non-AAES member
colleagues. CONCLUSIONS: Based on these data, the AAES members excelled with
respect to publications, citations, and research funding compared with
nonendocrine surgical faculty. These results demonstrate that endocrine surgeons
can contribute enormously to the overall academic mission. Therefore, more
surgical departments in the United States should consider establishing an
endocrine surgery program.
PMID- 29936979
TI - Not all operative experiences are created equal: a 19-year analysis of a single
center's case logs.
AB - BACKGROUND: Although national operative volumes have remained stable, surgical
educators should appreciate the changing experience of today's surgical
residents. We set out to evaluate operative volume trends at our institution and
study the impact of resident learning styles on operative experience. MATERIALS
AND METHODS: The Accreditation Council for Graduate Medical Education operative
log data from 1999 to 2017 for a single general surgery residency program were
examined. All residents completed the Kolb Learning Style Inventory. Statistical
analyses were performed using linear regression analysis, Student's t-test, and
Fischer's exact test. RESULTS: Over the study period, 106 general surgery
residents graduated from our program. There were 87% action learners and 13%
observation learners. Although there was no change in total major, total chief,
or total non-chief cases, a decrease in teaching assistant cases was observed.
Subcategory analysis revealed that there was an increase in operative volume on
graduation in the following categories: skin, soft tissue, and breast; alimentary
tract; abdomen; pancreas; operative trauma; pediatric; basic laparoscopy; complex
laparoscopy; and endoscopy with a concurrent decrease in liver, vascular, and
endocrine. Learning style analysis found that action learners completed
significantly more cases than observation learners in most domains in which
operative volume increased. CONCLUSIONS: While the operative volume at our center
remained stable over the study period, the experience of general surgery
residents has become narrowed toward a less subspecialized, general surgery
experience. These shifts may disproportionally impact trainees as observation
learners operate less than action learners. Residency programs should therefore
incorporate methods such as learning style assessment to identify residents at
risk of a suboptimal experience.
PMID- 29936980
TI - Prolonged operative duration is associated with complications: a systematic
review and meta-analysis.
AB - BACKGROUND: The aim of this study was to systematically synthesize the large
volume of literature reporting on the association between operative duration and
complications across various surgical specialties and procedure types. METHODS:
An electronic search of PubMed, Cochrane Central Register of Controlled Trials,
and Cochrane Database of Systematic Reviews from January 2005 to January 2015 was
conducted. Sixty-six observational studies met the inclusion criteria. RESULTS:
Pooled analyses showed that the likelihood of complications increased
significantly with prolonged operative duration, approximately doubling with
operative time thresholds exceeding 2 or more hours. Meta-analyses also
demonstrated a 14% increase in the likelihood of complications for every 30 min
of additional operating time. CONCLUSIONS: Prolonged operative time is associated
with an increase in the risk of complications. Given the adverse consequences of
complications, decreased operative times should be a universal goal for surgeons,
hospitals, and policy-makers. Future study is recommended on the evaluation of
interventions targeted to reducing operating time.
PMID- 29936981
TI - Facilitating factors in same-day discharge after pediatric laparoscopic
appendectomy.
AB - BACKGROUND: Appendicitis has been cited to be the most common abdominal disorder
that requires acute care surgery in the pediatric population. Enhanced Recovery
After Surgery protocols are multimodal perioperative care pathways designed to
achieve early recovery after surgical procedures by maintaining preoperative
organ function and reducing the profound stress response following surgery. Such
pathways have been found to enhance quality of care for surgical patients as well
as improve recovery and shorten hospital stays. The purpose of this study was to
determine the key factors that facilitate same-day discharge (SDD) and early
return to normal activities after laparoscopic appendectomies in children.
METHODS: This is a single-center retrospective chart review of pediatric patients
(<18 y old) who underwent appendectomies for acute appendicitis from January 2015
to April 2017. The patient population was divided into two groups: those with SDD
and those who were discharged one or more days after surgery. SDD was defined as
discharge less than 24 h of surgical admission. Patient factors, including
prehospital, preoperative, perioperative, and postoperative factors, were
compared and analyzed between the two groups and statistically evaluated using
Fisher's exact test for categorical data and student t-test for continuous
variables. RESULTS: Two hundred forty eight patients were found under
International Classification of Diseases-9 and International Classification of
Diseases-10 codes for acute appendicitis. Of these, 63 were excluded due to
perforated appendicitis, nonoperative management, interval appendectomies, or
misdiagnosis. The remaining 185 had laparoscopic appendectomies; 59.5% (n = 110)
were SDDs and 40.5% (n = 75) stayed more than one day. No significant difference
was found for time between emergency room arrival and surgical admission (5.27
versus 5.4 h; P = 08.) but SDD patients had a significantly shorter time between
surgical admission and operation (5.8 versus 11.4 h; P <0.001). SDD patients and
non-SDD patients had no significant difference in rate of complications (0%
versus 1.3%; P = 0.4). There was no significant difference in readmission rates
between the two groups (2.7% versus 2.7%; P = 1). Total hospital charges, which
indirectly reflect costs, were significantly less for SDD ($29,195 versus
$33,703; P <0.001). CONCLUSIONS: Surgical leadership can be effective in
facilitating SDD without increasing readmission rates or complications and helps
reduce hospital costs, decreases chances of nosocomial infection, and increases
patient and family satisfaction.
PMID- 29936982
TI - Reducing cost and improving operating room efficiency: examination of surgical
instrument processing.
AB - BACKGROUND: Operating room efficiency can be compromised because of surgical
instrument processing delays. We observed that many instruments in a standardized
tray were not routinely used during thyroid and parathyroid surgery at our
institution. Our objective was to create a streamlined instrument tray to
optimize operative efficiency and cost. MATERIALS AND METHODS: Head and neck
surgical instrument trays were evaluated by operating room team leaders.
Instruments were identified as either necessary or unnecessary based on use
during thyroidectomies and parathyroidectomies. The operating room preparation
time, tray weights, number of trays, and number of instruments were recorded for
the original and new surgical trays. Cost savings were calculated using estimated
reprocessing cost of $0.51 per instrument. RESULTS: Three of 13 head and neck
trays were converted to thyroidectomy and parathyroidectomy trays. The starting
head and neck surgical set was reduced from two trays with 98 total instruments
to one tray with 36 instruments. Tray weight decreased from 27 pounds to 10
pounds. Tray preparation time decreased from 8 min to 3 min. The new tray saved
$31.62 ($49.98 to $18.36) per operation in reprocessing costs. Projected annual
savings with hospitalwide implementation is over $28,000.00 for instrument
processing alone. Unmeasured hospital savings include decreased instrument wear
and replacement frequency, quicker operating room setup, and decreased
decontamination costs. CONCLUSIONS: Optimizing surgical trays can reduce cost,
physical strain, preparation time, decontamination time, and processing times,
and streamlining trays is an effective strategy for hospitals to reduce costs and
increase operating room efficiency.
PMID- 29936983
TI - The association between angioembolization and splenic salvage for isolated
splenic injuries.
AB - BACKGROUND: Recent data suggest improved splenic salvage rates when
angioembolization (AE) is routinely employed for high-grade splenic injuries;
however, protocols and salvage rates vary among centers. MATERIALS/METHODS: Adult
patients with isolated splenic injuries were identified using the National Trauma
Data Bank, 2013-2014. Patients were excluded if they underwent immediate
splenectomy or died in the emergency department. To characterize patterns of AE,
trauma centers were grouped into quartiles based on frequency of AE use.
Unadjusted analyses and mixed-effects logistical regression controlling for
center effects were performed. RESULTS: Five thousand and ninety three adult
patients were identified. Overall, 705 (13.8%) underwent AE and 290 (5.7%)
required a splenectomy. In unadjusted comparisons, splenectomy rates were lower
for patients with severe spleen injuries who underwent AE (7% versus 11%, P =
0.02). In mixed-effect logistical regression patients with severe splenic
injuries undergoing AE had a lower odds ratio (OR) for splenectomy (OR = 0.67, P
= 0.04). Patients treated at centers in the highest quartile of AE use had a
lower OR for splenectomy (OR = 0.58, P = 0.02). CONCLUSIONS: The use of AE in
patients with isolated severe splenic injuries is associated with decreased
splenectomy rates. There is an association between centers that perform AE
frequently and reduced splenectomy rates.
PMID- 29936984
TI - Exposure to bile acids alters the intracellular location and function of MnSOD in
Barrett's esophagus.
AB - BACKGROUND: Oxidative stress secondary to bile-acid exposure has been associated
with metaplastic degeneration of normal esophageal mucosa into Barrett's
esophagus (BE) cells and eventually esophageal adenocarcinoma. We previously
reported that the macromolecular response of BE cells to this stress was largely
regulated by the expression of manganese-dependent mitochondrial superoxide
dismutase (MnSOD). As the mitochondrion plays a vital role in MnSOD activation,
this study sought to determine the location and activity of MnSOD within BE cells
after exposure to oxidative stress. METHODS: A human BE cell line, BAR-T cell,
was exposed 0.4 mM concentrations of taurocholic acid (Tau) or a 0.4 mM 1:1
mixture of bile salts for 4 h. Cell viability was performed with 3-(4, 5-dimthyl
thiazol-2-yl)-2, 5-diphenyltetrazolium bromide assays. Proteins were extracted
and separated into mitochondrial, nuclear, and cytoplasmic fractions followed by
analysis by a western blot and enzymatic activities. RESULTS: BAR-T cell showed
resistance to the bile-salt insults. Expression of MnSOD was significantly
increased in the cells exposed to a mixture of bile acids and Tau versus control.
Mitochondria MnSOD is abundant and highly active. Nuclear fraction displayed
presence of both MnSOD and Cu/zinc superoxide dismutase secondary to bile-acid
exposure; however, the MnSOD was inactive in nuclear fraction. CONCLUSIONS: This
is the first study to specifically evaluate cellular fraction MnSOD expression,
increased in BE cells in response to the oxidative stress of bile exposure.
Mitochondrial MnSOD contributes to resistance of BAR-T cells to the bile-salt
insults. Further investigation is required to determine the potential correlation
between bile exposure and BE to adenocarcinoma progression via MnSOD-mediated
cell signaling.
PMID- 29936985
TI - Surgeons have an opportunity to improve teaching quality through feedback
provision.
AB - BACKGROUND: Medical student evaluations of faculty are increasingly incorporated
into promotion and tenure decisions, making it imperative to understand learner
perceptions of quality teaching. Prior work has shown that students value faculty
responsiveness in the form of feedback, but faculty and students differ in their
perceptions of what constitutes sufficient feedback. The innovative minute
feedback system (MFS) can quantify responsiveness to students' feedback requests.
This study assessed how feedback provision via MFS impacts teaching quality
scores. MATERIALS AND METHODS: This retrospective observational study compared
average faculty teaching quality scores with faculty's percentage response to
student feedback requests via the MFS. The data were generated from the core
surgical clerkship for third-year medical students at the University of Michigan
Medical School. The relationship between average teaching quality scores and
response percentage was assessed by weighted regression analysis. RESULTS: Two
hundred thirty-seven medical students requested feedback via MFS, and 104 faculty
were evaluated on teaching quality. The mean faculty feedback response percentage
was 55.78%. The mean teaching quality score was 4.27 on a scale of 1 to 5.
Teaching quality score was significantly correlated with response percentage (P <
0.001); for every 10% increase in response percentage, average teaching quality
score improved by 0.075. Average teaching quality score was not significantly
associated with response time (P = 0.158), gender (P = 0.407), or surgical
service (P = 0.498). CONCLUSIONS: Medical students consider responsiveness to
feedback requests an important component of quality teaching. Furthermore,
faculty development focused on efficient and practical feedback strategies may
have the added benefit of improving their teaching quality.
PMID- 29936986
TI - Detection of free flap pedicle thrombosis by infrared surface temperature
imaging.
AB - BACKGROUND: Reliable detection of any circulatory issue threatening flap
viability after free flap surgery is essential for prompt flap salvage.
Currently, the gold standard of flap monitoring is clinical monitoring. However,
this method presents logistical challenges to insufficient trained personnel.
Auxiliary methods are becoming increasingly vital. MATERIALS AND METHODS: Twelve
swine pedicle myocutaneous flaps were harvested and monitored using infrared
cameras to investigate the developed monitoring parameters and vascular
thrombosis in the free flap model. RESULTS: The mean flap surface temperature
after vein or artery occlusion decreased significantly, but the differences were
relatively small. As a result, the difference between recorded (flap surface
temperature [Ts]) and predicted (estimated surface temperature [Tes]) flap
surface temperature (DeltaT = Ts- Tes) was used as the parameter for pedicle
thrombosis. A DeltaT of <0.86 degrees C was used as a vascular occlusion
criterion; the sensitivity and specificity of this parameter were 90% and 81%,
respectively. The standard deviation of the surface temperature (SDT) was another
indicator of vascular occlusion; the estimated sensitivity and specificity for
vessel occlusion of SDT < 0.48 degrees C were 84% and 73%, respectively.
CONCLUSIONS: Infrared thermal imaging has the advantages of being noninvasive,
contact-free, continuous, and able to detect the whole flap surface area. Two
indicators, DeltaT and SDT, can be used with high sensitivity and specificity for
early prediction of flap pedicle thrombosis. Further human studies are necessary
to validate clinical application of infrared thermal imaging.
PMID- 29936987
TI - Sex-dependent outcomes following elective endovascular aortic repair.
AB - BACKGROUND: Evidence has shown that women derive less benefit from endovascular
aortic repair (EVAR) in large part due to more challenging aortoiliac anatomy.
This study sought to examine whether sex-dependent outcomes exist following
elective EVAR cases. METHODS: An institutional retrospective review was performed
on patients who underwent elective EVAR procedures between 2008 and 2014. Outcome
data collected included procedural and hospital morbidity, mortality, and overall
EVAR durability based on the incidence of unplanned graft-related secondary
interventions (SIs) (e.g., open conversion, proximal or distal extensions, and
coil embolizations). RESULTS: One hundred eighty-one patients (150 men, 31 women)
met the study inclusion criteria. Median follow-up was 40.3 mo. Women had more
challenging anatomy compared to men including smaller overall iliac diameters
(6.8 mm versus 8.0 mm, P < 0.001) and more severe iliac angulation (77% moderate
to severe versus 44%, P < 0.001). Women had increased risk of postoperative
complications compared to men (41.9% versus 11.3%, P = 0.003). There was no
perioperative mortality in our series of elective EVAR cases. Median 5-y survival
following EVAR was 64.4% for men and 76.3% for women (P = 0.599). Late SI rates
following EVAR was 10.5% with 16 (10.7%) men and 3 (9.7%) women needing
interventions (P = 0.870). Overall durability of EVAR extrapolated as time to SIs
was 91% at 2 y and 85% at 5 y. Factors predisposing SIs were iliac tortuosity (P
= 0.046), aortic neck angle (P = 0.022), and endoleak at the follow-up (P =
0.030). CONCLUSIONS: In this study, immediate outcomes following EVAR were
different between men and women, with women having increased rates of
postoperative complications. Mortality and overall long-term durability of EVAR,
however, were the same between sexes despite anatomical differences. EVAR
durability was significantly dependent on the severity of iliac tortuosity,
aortic neck angulation, and presence of endoleak at the follow-up.
PMID- 29936988
TI - Cost and outcomes of open versus laparoscopic cholecystectomy in Mongolia.
AB - BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard of care for biliary
disease in developed countries. LC in resource-limited countries is increasing.
This prospective, observational study evaluates costs, outcomes, and quality of
life (QoL) associated with laparoscopic versus open cholecystectomy (OC) in
Mongolia. METHODS: Patient demographics, outcomes, and total payer and patient
costs were elicited from a convenience sample of patients undergoing
cholecystectomy at four urban and three rural hospitals (February 2016-January
2017). QoL was assessed preoperatively and postoperatively using the five-level
EQ-5D instrument. Perioperative complications, surgical fees, and QoL scores were
evaluated for LC versus OC. Multivariate regression models were generated to
adjust for differences between these groups. RESULTS: Two hundred and fifteen
cholecystectomies were included (LC 122, OC 93). LC patients were more likely to
have attended college and have insurance. Preoperative symptoms were comparable
between groups. Total complication rate was 21.8% (no difference between groups);
LC patients had less superficial infections (0% versus 10.8%). Median hospital
length of stay (HLOS) and days to return to work were shorter after LC. QoL
improved after surgery for both groups. Mean total payer and patient costs were
higher for LC, but not significant (P-value 0.126). After adjustment, LC had
significantly less complications, shorter HLOS, fewer days to return to work,
greater improvement in QoL scores, and no increase in cost. CONCLUSIONS: LC is
safe and beneficial to patients with biliary disease in Mongolia, and cost
effective from the patient's and payer's perspective. Although equipment costs
for LC may be more expensive than OC, there are likely significant cost savings
related to reduced HLOS, shorter time off work, fewer complications, and improved
QoL.
PMID- 29936989
TI - Repair of injured urethras with silk fibroin scaffolds in a rabbit model of onlay
urethroplasty.
AB - BACKGROUND: Preclinical validation of scaffold-based technologies in animal
models of urethral disease is desired to assess wound healing efficacy in
scenarios that mimic the target patient population. This study investigates the
feasibility of bilayer silk fibroin (BLSF) scaffolds for the repair of previously
damaged urethras in a rabbit model of onlay urethroplasty. MATERIALS AND METHODS:
A focal, partial thickness urethral injury was created in adult male rabbits (n =
12) via electrocoagulation and then onlay urethroplasty with 50 mm2 BLSF grafts
was carried out 2 wk after injury. Animals were randomly divided into three
experimental groups and harvested at 2 wk after electrocoagulation (n = 3), and 1
(n = 3) or 3 (n = 6) months after scaffold implantation. Outcome analyses were
performed preoperatively and at 2 wk after injury in all groups as well as at 1
or 3 mo after scaffold grafting and included urethroscopy, retrograde
urethrography (RUG), and histological and immunohistochemical analyses. RESULTS:
At 2 wk after electrocoagulation, urethroscopic and RUG evaluations confirmed
urethral stricture formation in 92% (n = 11/12) of rabbits. Gross tissue
assessments at 1 (n = 3) and 3 (n = 6) mo after onlay urethroplasty revealed host
tissue ingrowth covering the entire implant site. At 3 mo post-op, RUG analyses
of repaired urethral segments demonstrated a 39% reduction in urethral stenosis
detected following electrocoagulation injury. Histological and
immunohistochemical analyses revealed the formation of innervated, vascularized
neotissues with alpha-smooth muscle actin+ and SM22alpha+ smooth muscle bundles
and pan-cytokeratin + epithelium at graft sites. CONCLUSIONS: These results
demonstrate the feasibility of BLSF matrices to support the repair of previously
damaged urethral tissues.
PMID- 29936990
TI - Thyroidectomy in older adults: an American College of Surgeons National Surgical
Quality Improvement Program study of outcomes.
AB - BACKGROUND: The growth of the US geriatric population coupled with the rise in
thyroid nodular disease and cancer will result in an increased number of
thyroidectomies performed in older adults. We aim to evaluate outcomes after
thyroidectomy in older adults as compared with younger adults. METHODS: A
retrospective cohort study using the American College of Surgeons National
Surgical Quality Improvement Program database from 2012-2015 categorized
thyroidectomy patients into three age groups: 18-64 y, 65-79 y, and >=80 y.
Thirty-day perioperative outcomes were analyzed using bivariate chi2 test and
multivariate logistic regression to estimate risk of outcomes. RESULTS: Our study
identified 60,990 patients who underwent thyroidectomy: 47,855 (78.4%) patients
between 18 and 64 y old, 11,716 (19.2%) between 65 and 79 y old, and 1419 (2.3%)
>=80 y. Compared with younger adults, patients aged >=80 y were 2.67 times more
likely to develop a complication (95% confidence interval [CI]: 2.02-3.53, P <
0.001), 1.83 times more likely to be readmitted for any reason (95% CI: 1.40
2.38, P < 0.001), 1.54 times more likely to be readmitted for a reason related to
the thyroidectomy (95% CI: 1.10-2.16, P < 0.05), and 1.66 times more likely to
have an extended hospital stay (95% CI: 1.44-1.91, P < 0.001). Patients aged 65
79 y were 1.40 times more likely to develop a complication (95% CI: 1.19-1.63, P
< 0.001). CONCLUSIONS: Patients aged >=65 y have significantly higher rates of
overall complications. In addition, patients aged >=80 y have higher rates of
total and thyroidectomy-related readmissions and extended length of hospital
stay.
PMID- 29936991
TI - Surgical management of hidradenitis suppurativa: procedural trends and risk
factors.
AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic debilitating cutaneous
disorder. The recalcitrant nature of this disease may require surgery in severe
cases. We aimed to delineate the types of operations performed, the risk factors
associated with these operations, and the surgical services involved based on a
national database. METHODS: Data were collected through the American College of
Surgeons National Surgical Quality Improvement Program from 2011 to 2016. Current
Procedural Terminology (CPT) and International Classification of Disease, Ninth
Revision, (ICD-9) codes were used for data extraction and analysis as type of
surgery and complication rates were extracted. RESULTS: There were 2594 patients
diagnosed with HS: 1405 (54.2%) incision and drainage, 1017 (39.2%) debridement,
31 (1.2%) skin graft, and 141 (5.4%) flap reconstruction. There were significant
differences in transfusion rates and operation time among the four procedures.
Skin graft and flap reconstruction had the highest complications and longest
operation time. Bleeding requiring preoperative transfusion and a number of
comorbidities were significant risk factors for postoperative complications. Flap
reconstructions by plastic surgeons compared to general surgeons had
significantly shorter operation times (134.89 versus 209.82 min, P = 0.022) and
lower transfusion rates (2.2% versus 12.8%, P = 0.024). CONCLUSIONS: The
management of HS can be complex and may require a multidisciplinary approach.
Bleeding requiring preoperative transfusion and other baseline comorbidities are
independent risk factors that should be addressed when definitive surgical
treatment of hidradenitis is planned. Appropriate surgical specialty involvement
may better optimize the surgical outcomes for HS.
PMID- 29936992
TI - Multidisciplinary strategies in bloodless medicine and surgery for patients
undergoing pancreatectomy.
AB - BACKGROUND: Bloodless pancreatic surgery (BPS) is rarely performed and/or
reported. We aim to characterize perioperative and anesthetic strategies in BPS.
MATERIALS AND METHODS: A literature search was performed on MEDLINE looking for
case reports/case series using search terms ("Jehovah's Witness" [All Fields])
AND ("Pancreatic Surgery" [All Fields] OR "Pancreaticoduodenectomy" [All Fields]
OR "Distal Pancreatectomy" [All Fields]). Data regarding categorical variables
are reported as proportions and quantitative continuous variables as medians with
ranges or means with standard deviation. Forty-one patients requiring BPS are
reported in the literature with three additional cases from our institution (n =
44). The data analyzed included clinicopathologic factors, BPS strategies,
patient complications, and in-hospital mortality. RESULTS: The most common
procedure and diagnosis were pancreaticoduodenectomy (n = 34, 77.3%) and
pancreatic ductal adenocarcinoma (n = 12, 27.3%), respectively. Transfusion
reduction strategies in BPS fell into three categories: preoperative,
intraoperative, and postoperative. Preoperative strategies included iron
supplementation (n = 24, 54.5%) and erythropoietin administration (n = 14,
41.2%). Intraoperative strategies included acute normovolemic hemodilution (n =
30, 68%) and cell saver (n = 4, 9.1%). Postoperative strategies included
erythropoietin (n = 16, 48.5%) and iron supplementation (n = 16, 48.5%).
Complications occurred in 21 (60%) patients. There was no in-hospital mortality
among the 44 patients in this cohort. CONCLUSIONS: A broad spectrum of bloodless
medicine and surgery practices were used based on patient selection,
multidisciplinary practice, and preference. With careful perioperative and
anesthetic management, BPS can be performed with good outcomes.
PMID- 29936993
TI - Correlation of payor status and pediatric transfer for acute appendicitis.
AB - BACKGROUND: Tertiary referral centers provide specialty and critical care for
patients presenting to hospitals that lack these resources. There is a notion
among tertiary centers that outside hospitals are more likely to transfer
uninsured or underinsured patients. We examined funding status of patients
transferred to our tertiary pediatric hospital for surgical management of
appendicitis, hypothesizing that transferred patients were more likely to have
unfavorable coverage. MATERIALS AND METHODS: The electronic medical record was
queried for all cases of laparoscopic appendectomy at our hospital between 2011
and 2015. Insurance was grouped into three categories: commercial,
Medicaid/Children's Health Insurance Plan, or none. Transferred patients were
compared to patients who presented directly. RESULTS: A total of 5758 patients
underwent laparoscopic appendectomy during the study period, of which 1683
(29.2%) were transfer patients. Transfer patients were more likely to be older,
with a median age of 10.5 y versus 9.8 y in nontransferred patients (P <=
0.0001), and were more likely to be identified as non-Hispanic (50.0% versus
36.5%; P <= 0.0001). Insurance coverage was similar between groups. However,
subgroup analysis of the hospitals that most frequently used our transfer
services revealed a trend to transfer a higher proportion of Medicaid/Children's
Health Insurance Plan patients. CONCLUSIONS: Overall, pediatric patients
transferred for laparoscopic appendectomy had similar insurance coverage to
patients admitted directly, but subgroup analysis shows that not all centers
follow this trend. Transfer patients were more frequently older and non-Hispanic.
This builds upon the existing literature regarding the correlation of funding and
transfer practices and highlights the need for additional research in this area.
PMID- 29936994
TI - Clinical characteristics and surgical outcomes of dysfunctional quadricuspid
aortic valve.
AB - BACKGROUND: Quadricuspid aortic valve (QAV) is a rare and poorly understood
congenital cardiac abnormality. This study aims to evaluate the clinical features
and surgical outcomes of dysfunctional QAV. METHODS: From January 2011 to May
2017, 36 (mean age 50.7 +/- 11.9 y, 19 males) of a total of 3855 patients who
underwent aortic valve surgery were identified as having dysfunctional QAV
(frequency 0.9%). All patients presented moderate or severe aortic regurgitation,
and nine patients (25.0%) had concomitant aortic stenosis. The ascending aortic
diameter was over 40 mm in seven patients (19.4%) and over 45 mm in two patients
(5.6%). The most common QAV morphology was type B (n = 12, 33.3%) according to
the Hurwitz-Roberts classification. RESULTS: All patients underwent aortic valve
replacement and two required concomitant ascending aortic replacement. The mean
follow-up time was 20.6 +/- 14.2 mo. There was no early or late postoperative
mortality or major complications. Pathological analysis of dilated ascending
aorta demonstrated a relatively normal appearance. The ascending aorta did not
grow after surgery (37.3 +/- 4.1 mm versus 36.1 +/- 2.5 mm, P = 0.084). Both the
end-diastolic (58.1 +/- 7.0 mm versus 50.0 +/- 6.3 mm, P < 0.001) and end
systolic (37.7 +/- 6.7 mm versus 32.8 +/- 6.0 mm, P < 0.001) left ventricular
dimensions were significantly decreased. CONCLUSIONS: Aortic insufficiency is the
predominant pathology in dysfunctional QAV patients. The incidence and extent of
aortic dilation is not significant in QAV and not associated with aortic valve
phenotypes. Short- and mid-term surgical outcomes were found to be satisfactory
in this study.
PMID- 29936995
TI - Clopidogrel bisulfate (Plavix) does not increase bleeding complications in
patients undergoing rubber band ligation for symptomatic hemorrhoids.
AB - BACKGROUND: The incidence of postprocedural bleeding in patients undergoing
rubber band ligation (RBL) for symptomatic internal hemorrhoids while taking
clopidogrel bisulfate is unknown. To determine the postprocedural bleeding risk
of RBL for patients taking clopidogrel compared with age- and sex-matched
controls. MATERIALS AND METHODS: This is a retrospective case-controlled cohort
study analyzing data from 2005 to 2013 conducted at a single tertiary care
academic center. The study included a total of 80 rubber bands placed on 41
patients taking clopidogrel bisulfate and 72 bands placed on 41 control patients
not taking clopidogrel matched for age and sex. The 30-d rates of significant and
insignificant bleeding events after RBL were recorded. A bleeding event was
considered significant if the patient required admission to the hospital,
transfusion of blood products, or additional procedures to stop the bleeding.
Insignificant bleeding was defined as passage of blood or clots per rectum with
spontaneous cessation and no need for additional intervention. RESULTS: There was
no significant difference in the number of bleeding events per band placed in the
clopidogrel group when compared with the control group (3.75% versus 2.78%, P =
0.7387). The rate of significant (2.5% versus 1.39%, P = 0.6244) and
insignificant bleeding events (1.25% versus 1.39%, P = 0.9399) was also similar
between the two groups. Two significant bleeding events occurred in the
clopidogrel group requiring intervention: cauterization in one patient and
colonoscopy and transfusion in the other. CONCLUSIONS: The risk of a bleeding
complication after RBL for hemorrhoids does not appear to be increased in
patients taking clopidogrel. Our results support the practice of continuing
clopidogrel bisulfate in the periprocedural period as the associated risk of
thrombosis is greater than the risk of bleeding.
PMID- 29936996
TI - Population-level outcomes of early versus delayed appendectomy for acute
appendicitis using the American College of Surgeons National Surgical Quality
Improvement Program.
AB - BACKGROUND: The optimal timing of appendectomy for acute appendicitis has been
analyzed with mixed results. We hypothesized that delayed appendectomy would be
associated with increased 30-d morbidity and mortality. MATERIALS AND METHODS:
The American College of Surgeons National Surgical Quality Improvement Program
database was queried for all patients undergoing nonelective appendectomy from
2012 to 2015 with a postoperative diagnosis of appendicitis. Patients were
grouped based on hospital day (HD) of operation. Primary outcomes included 30-d
mortality and major complications. Logistic regression was performed to determine
predictors of major morbidity and mortality. RESULTS: From 2012 to 2015, 112,122
patients underwent appendectomy for acute appendicitis. Appendectomies performed
on HD 3 had significantly worse outcomes as demonstrated by increased 30-d
mortality (0.6%) and all major postoperative complications (8%) in comparison
with operations taking place on HD 1 (0.1%; 3.4%) or HD 2 (0.1%, P < 0.001; 3.6%,
P < 0.001). In subgroup analysis, open operations had significantly higher
mortality and major postoperative complications, including organ/space surgical
site infections (4.6% open versus 2.1% laparoscopic; P < 0.001). Patients with
decreased baseline physical status by the American Society of Anesthesiologists
Physical Status class had the worst outcomes (1.5% mortality; 14% major
complications) when operation was delayed to HD 3. Logistic regression revealed
higher American Society of Anesthesiologists Physical Status class and open
operations as predictors of major complications; however, HD was not (P = 0.2).
CONCLUSIONS: Data from the American College of Surgeons National Surgical Quality
Improvement Program demonstrate similar outcomes of appendectomy for acute
appendicitis when the operation is performed on HD 1 or 2; however, outcomes are
significantly worse for appendectomies delayed until HD 3. Increased
complications in this group are likely not attributable to HD of operation, but
rather decreased baseline health status and procedure type.
PMID- 29936997
TI - Adipose stem cells enhance excisional wound healing in a porcine model.
AB - BACKGROUND: Adipose-derived stem cells (ASCs) are capable of secreting
regenerative growth factors and replacing multiple tissue types. Although current
literature suggests that ASCs accelerate wound healing and reduce scarring, the
dose-response relationship has not been adequately investigated in large animals.
We sought to establish a porcine model to optimize dose and delivery. METHODS:
Four-centimeter circular, full thickness excisional wounds were created on the
backs of Yorkshire pigs. Fluorescently labeled allogeneic porcine ASCs were
injected into the superficial wound bed and around the wound perimeter at high
(3.0 * 106 cells/cm2; n = 8), medium (1.0 * 106 cells/cm2; n = 8), and low (0.3 *
106 cells/cm2; n = 8) doses. Control wounds received saline injections (n = 8) or
no treatment (n = 8). Dressings were changed twice per week, and wound closure
was tracked by surface area tracing. Animals were sacrificed at 1 and 2 wk.
Wounds were harvested for real-time quantitative reverse transcriptase polymerase
chain reaction, immunohistochemistry, and ASC tracking. RESULTS: Labeled ASCs
integrated into treated wounds by 1 wk in a dose-dependent fashion. Epithelial
coverage was achieved by 14 d in all wounds. Wounds receiving high-dose ASCs
exhibited thicker granulating neodermis at 7 d and greater wound contraction at
14 d. real-time quantitative reverse transcriptase polymerase chain reaction
revealed improved collagen 1:collagen 3 (Col1:Col3) ratio in the medium-dose
group and enhanced alpha-smooth muscle actin in the high-dose group at 14 d.
Western blot demonstrated increased cluster of differentiation 31 protein at 2 wk
in wounds receiving >106 cells/cm2. CONCLUSIONS: Doses up to 3.0 * 106 cells/cm2
were well-tolerated. High-dose ASCs accelerate wound contraction, enhance
neovascularization, and may improve scar quality in excisional wounds healing by
secondary intention. Doses greater than those previously used may be necessary to
achieve desired effects.
PMID- 29936998
TI - Effects of different foods on blood glucose and lipid in type 2 diabetes mellitus
in a rat model.
AB - BACKGROUND: This study investigated the effects of duodenal-jejunal bypass (DJB)
and new biliopancreatic diversion (NBPD) on blood glucose and lipid levels in
type 2 diabetes mellitus (T2DM). An additional goal was to explore the potential
mechanism or mechanisms underlying the therapeutic effects of surgery on T2DM.
METHODS: Rats were fed a high-fat, high-glucose diet and then were
intraperitoneally injected with streptozotocin, 35 mg/kg, to induce T2DM. Then,
33 T2DM rats were randomly assigned to one of three groups, a DJB group, an NBPD
group, or a sham group. Fasting body weight, fasting glucose, and 2-h
postprandial glucose were measured before and after surgery. Then, the rats were
intragastrically administered lipid emulsion, peanut oil, glucose, starch, and
Ansul, and blood glucose and lipid levels were measured. RESULTS: One week after
surgery, 2-h postprandial glucose decreased from 24.41 +/- 2.28 mmol/L before
surgery to 19.87 +/- 4.07 mmol/L after surgery in the DJB group, and from 25.88
+/- 1.91 mmol/L before surgery to 20.34 +/- 5.76 mmol/L after surgery in the NBPD
group. After intragastric administration of lipid emulsion, free fatty acid
levels increased from 534.60 +/- 70.99 to 1082.83 +/- 259.67 MUEq/L in the DJB
group and from 648.33 +/- 139.26 to 1258.67 +/- 204.18 MUEq/L in the NBPD group.
After surgery, free fatty acid levels in the DJB group and NBPD group were
significantly lower than those in the sham group. CONCLUSIONS: Postprandial blood
glucose and lipids decreased after DJB and NBPD, which may be ascribed to
postoperative changes in digestion and absorption.
PMID- 29936999
TI - Trauma and hemorrhagic shock activate molecular association of 5-lipoxygenase and
5-lipoxygenase-Activating protein in lung tissue.
AB - BACKGROUND: Post-traumatic lung injury following trauma and hemorrhagic shock
(T/HS) is associated with significant morbidity. Leukotriene-induced inflammation
has been implicated in the development of post-traumatic lung injury through a
mechanism that is only partially understood. Postshock mesenteric lymph returning
to the systemic circulation is rich in arachidonic acid, the substrate of 5
lipoxygenase (ALOX5). ALOX5 is the rate-limiting enzyme in leukotriene synthesis
and, following T/HS, contributes to the development of lung dysfunction. ALOX5
colocalizes with its cofactor, 5-lipoxygenase-activating protein (ALOX5AP), which
is thought to potentiate ALOX5 synthetic activity. We hypothesized that T/HS
results in the molecular association and nuclear colocalization of ALOX5 and
ALOX5AP, which ultimately increases leukotriene production and potentiates lung
injury. MATERIALS AND METHODS: To examine these molecular interactions, a rat
T/HS model was used. Post-T/HS tissue was evaluated for lung injury through both
histologic analysis of lung sections and biochemical analysis of bronchoalveolar
lavage fluid. Lung tissue was immunostained for ALOX5 and ALOX5AP with
association and colocalization evaluated by fluorescence resonance energy
transfer. In addition, rats undergoing T/HS were treated with MK-886, a known
ALOX5AP inhibitor. RESULTS: ALOX5 levels increase and ALOX5/ALOX5AP association
occurred after T/HS, as evidenced by increases in total tissue fluorescence and
fluorescence resonance energy transfer signal intensity, respectively. These
findings coincided with increased leukotriene production and with the
histological changes characteristic of lung injury. ALOX5/ALOX5AP complex
formation, leukotriene production, and lung injury were decreased after
inhibition of ALOX5AP with MK-886. CONCLUSIONS: These results suggest that the
association of ALOX5/ALOX5AP contributes to leukotriene-induced inflammation and
predisposes the T/HS animal to lung injury.
PMID- 29937000
TI - Comparability of histological outcomes in rats and humans in a hernia model.
AB - BACKGROUND: Hernia repair is one of the most frequently performed operations. In
search of the ideal mesh for hernia repair, animal research is required. Although
rats are most often used in experimental mesh experiments, no correlation with
clinical findings in humans has ever been shown. Therefore, the aim of our study
was to investigate whether adhesion formation and foreign body reactions to
meshes in rats are comparable with the reactions in humans. MATERIALS AND
METHODS: A fixed type of mesh was implanted intraperitoneally in a group of 10
rats and 10 patients undergoing elective, temporary stoma formation. In case of
the latter, meshes were placed around the stoma. After a follow-up period of 12
wk in rats and after a median follow-up of 6 mo in humans, samples of the mesh
were collected. Adhesion assessments were performed, and (immuno-) histochemical
evaluation was performed by a specialized experimental pathologist and an
experienced clinical pathologist. RESULTS: After the follow-up period, adhesion
formation did not differ significantly between rats and humans. Moreover, general
inflammation scores were comparable, although granulocytes and giant cells were
more present in rats, compared with humans. On the other hand, the presence of
fibrosis was more evident in humans compared with rats. CONCLUSIONS: To our
knowledge, this is the first study, which showed that a specific animal model,
namely a rat model, correlates with adhesion formation and the foreign body
reaction to meshes in humans. It can be recommended to use rats in future
experimental mesh for incisional hernia research.
PMID- 29937001
TI - Comparison of two different models of sepsis induced by cecal ligation and
puncture in rats.
AB - BACKGROUND: The present study was designed to explore the difference between two
rat models of sepsis and to establish a more stable rat model. MATERIALS AND
METHODS: Sprague-Dawley rats were randomly divided into three groups: sham
operation group, simple cecal ligation and perforation group (SCLP), and cecal
ligation perforation plus drainage group (CLP-DS). The general condition of the
rats was observed, and the time of death and survival rate at 72 h were recorded.
The arterial blood and lung tissue were obtained 9 h after the operation.
RESULTS: The mortality of the CLP-DS group was significantly higher than that of
the SCLP group. The limitation package, intestinal adhesion, and poor drainage
were detected in the SCLP rats, whereas intestinal edema and hyperemia, bloody
water in the abdominal cavity, but no inflammatory package were observed 24 h
after the operation in the CLP-DS rats by autopsy. There were significant
differences in interleukin-6 and tumor necrosis factor-alpha levels between the
SCLP group and the CLP-DS group. Severe pulmonary septal thickening, alveolar
wall vascular congestion, and protein debris deposition in the alveolar cavity
were observed in the SCLP group, whereas pulmonary bullae were observed in the
CLP-DS group using light microscopy, and there were significant difference among
groups in Smith lung injury score. CONCLUSIONS: These results suggested that the
cecal ligation combined with puncture drainage model of sepsis is more stable
than that of the simple cecal ligation and puncture model of sepsis in the rat,
which resolved the problem of puncture wrapped in the traditional CLP model of
sepsis in rat.
PMID- 29937002
TI - CRISPR/Cas and recombinase-based human-to-pig orthotopic gene exchange for
xenotransplantation.
AB - BACKGROUND: Tools for genome editing in pigs are improving rapidly so that making
precise cuts in DNA for the purposes of deleting genes is straightforward.
Development of means to replace pig genes with human genes with precision is very
desirable for the future development of donor pigs for xenotransplantation.
MATERIALS AND METHODS: We used Cas9 to cut pig thrombomodulin (pTHBD) and replace
it with a plasmid containing a promoterless antibiotic selection marker and the
exon for human thrombomodulin. PhiC31 recombinase was used to remove the
antibiotic selection marker to create porcine aortic endothelial cells expressing
human instead of pTHBD, driven by the endogenous pig promoter. RESULTS: The
promoterless selection cassette permitted efficient enrichment of cells
containing correctly inserted transgene. Recombinase treatment of selected cells
excised the resistance marker permitting expression of the human transgene by the
endogenous pTHBD promoter. Gene regulation was maintained after gene replacement
because pig endogenous promoter was kept intact in the correct position.
CONCLUSIONS: Cas9 and recombinase technology make orthotopic human for pig gene
exchange feasible and pave the way for creation of pigs with human genes that can
be expressed in the appropriate tissues preserving gene regulation.
PMID- 29937003
TI - Patterns of opioid use and prescribing for outpatient anorectal operations.
AB - BACKGROUND: Surgery for anorectal diseases is thought to cause significant pain
postoperatively. There is little known regarding standardized opioid-prescribing
trends and patient use following surgery for anorectal diseases. We aimed to
evaluate and analyze opioid-prescribing trends and patient use for outpatient
anorectal operations. MATERIALS AND METHODS: All patients who underwent
outpatient anorectal surgery performed over a 1-y period at a single institution
were eligible. Procedures included hemorrhoidectomy, anal fistula repair/seton,
anal fissure treatment with sphincterotomy, and transanal excision of rectal
tumors. Demographic, operative, and postoperative data were obtained. Patients
were given a survey to determine postoperative pain control with opioid and non
narcotic analgesia use; respondents were included in analysis. RESULTS: Forty-two
outpatient anorectal surgery patients were included: 13 had hemorrhoidectomy, 22
had anal fistula repair/seton, one had sphincterotomy, and six had transanal
excisions. All patients had multimodality treatment with either an anal block
and/or postoperative nonopioid analgesics. Ninety percent were prescribed opioids
postoperatively with a median of 20 pills (range: 0-120 pills). Forty-three
percent (18/42) did not fill their prescription. For those who used opioids, the
median number of pills taken was four. Eighty percent of pills prescribed were
not used. One patient required a refill. Greater than 60% of respondents reported
good to excellent pain control on a five-point scale. CONCLUSIONS: Most patients
had adequate pain control after anorectal surgery with little to no use of
opioids and that more than 80% of opioid pills prescribed were not consumed. We
intend to standardize our prescribing opioid quantities for outpatient anorectal
operations to reflect this reduced use.
PMID- 29937004
TI - Anemia and blood transfusion in elderly trauma patients.
AB - BACKGROUND: The natural history of postinjury among elderly trauma patients has
not been well described. We hypothesized that elderly trauma patients would have
lower admission hemoglobin (Hb) levels, higher transfusion rates, and worse
outcomes than young trauma patients. METHODS: We performed a propensity-matched
retrospective cohort analysis comparing elderly (age >=65 y) to young (age 18-64)
trauma patients matched by sex, mechanism of injury, Injury Severity Score, base
deficit, comorbidities, operative blood loss, and phlebotomy blood loss (n =
41/group). Outcomes included Hb trends, packed red blood cell (PRBC) transfusion,
length of stay, and mortality. RESULTS: Elderly patients had lower admission Hb
(11.3 versus 10.2 g/dL, P = 0.012), received more PRBC transfusions within 24 h
(3.6 versus 1.8 units, P = 0.046), and during admission (6.9 versus 4.3 units, P
= 0.008). Despite receiving more PRBC transfusions and having similar operative
and phlebotomy blood loss, elderly subjects had lower discharge Hb (9.0 versus
9.7 g/dL, P = 0.013). Elderly subjects had fewer ICU-free days (2.0 versus 6.0 d,
P < 0.001) and higher in-hospital mortality (15% versus 0%, P = 0.026).
CONCLUSIONS: Elderly trauma patients had lower admission Hb, received more
transfusions, and had persistently lower Hb on discharge when controlling for
injury severity, comorbid conditions, and blood loss. Aging may have a negative
impact on postinjury anemia.
PMID- 29937005
TI - Programmatic change leads to enhanced resource utilization and efficiency in port
placement.
AB - BACKGROUND: Central venous port (CVP) placement is performed by a variety of
surgeons in different subspecialties, and our previous work suggests that
individual surgeons-regardless of training-are the strongest predictor of
outcomes. We sought to prospectively evaluate a programmatic shift toward a
resource-conscious, patient-focused algorithm for this common and simple surgical
procedure. MATERIALS AND METHODS: After implementation of a systems-level program
for efficient CVP placement, 78 CVPs were placed by a single surgeon. Primary
outcomes were procedure time, total operating room (OR) time, total facility
time, and procedure-related complications. These prospective data were compared
with retrospective cohorts of surgically placed and interventional radiology
placed CVP. Demographic data were analyzed by chi-square analysis, whereas time
data were analyzed by the Wilcoxon rank-sum test. RESULTS: The programmatic
delivery (prospective) set showed significantly shorter procedural (median 16 min
versus 26-40, P <0.05), OR times (median 36 min versus 46-70, P <0.05), and
facility times (median 235 min versus 299-319, P <0.05) except for the
interventional radiology facility time (median 187 versus 235, P <0.05). The
range of OR time savings with the prospective versus comparison groups was 10-34
min, representing 22%-49% reductions in OR time (P <0.05). Complication rates
were not significantly different (P = 0.13). CONCLUSIONS: Through a programmatic
change emphasizing efficiency and patient-centered outcomes,
procedural/OR/facility time can be reduced greatly without changing complication
rates. These data provide compelling evidence that common and ostensibly simple
operative procedures can be substantially improved upon with thoughtful, data
driven systems-level enhancements.
PMID- 29937006
TI - Development of murine bariatric surgery models: lessons learned.
AB - Roux-en-Y gastric bypass (RYGB) improves comorbidities such as diabetes and
hypertension and lowers the risk of obesity-related cancers. To better understand
the physiologic and genetic influences of bariatric surgery, a reliable murine
model is needed that can be extended to genetically engineered mice. Given the
complexity of these procedures, few researchers have successfully implemented
these techniques beyond larger rodent models. The purpose of our study was to
develop a technically feasible and reproducible murine model for RYGB and sleeve
gastrectomy (SG). Mice were converted to liquid diet perioperatively without
fasting and housed in groups on raised wire platforms. SG involved significant
reduction of stomach volume followed by multilayer repair of the gastrotomy. RYGB
procedure consisted of side-to-side, functional end-to-side bowel anastomoses and
exclusion of the stomach medial to the gastroesophageal junction. Sham surgeries
consisted of enterotomies and gastrotomy followed by primary repair without
resection or rerouting. Survival after incorporation of the aforementioned
techniques was 100% in the SG group and 41% in the RYGB group at 1 mo after
surgery. Only 26% of RYGB mortality was attributed to leak, obstruction, or
stricture; the majority of postoperative mortality was due to stress, dumping, or
malnutrition. Much of the survival challenge for this surgical model was related
to perioperative husbandry, which is to be expected given their small stature and
poor response to stress. Utilization of the perioperative and surgical techniques
described will increase survival and feasibility of these technically challenging
procedures, allowing for a better understanding of mechanisms to explain the
beneficial effects of bariatric surgery.
PMID- 29937007
TI - Fetal tracheal occlusion in mice: a novel transuterine method.
AB - BACKGROUND: Fetal tracheal occlusion (TO) is an emerging surgical therapy in
congenital diaphragmatic hernia that improves the fetal lung growth. Different
animal models of congenital diaphragmatic hernia and TO present advantages and
disadvantages regarding ethical issues, cost, surgical difficulty, size, survival
rates, and available genetic tools. We developed a minimally invasive murine
transuterine TO model, which will be useful in defining how TO impacts lung
molecular biology, cellular processes, and overall lung physiology. MATERIALS AND
METHODS: Time-mated C57BL/6 mice underwent laparotomy at embryonic day 16.5
(E16.5) with transuterine TO performed on two fetuses in each uterine horn. At
E18.5, dams were sacrificed and fetuses harvested. The lungs of the TO fetuses
were compared with the nonmanipulated counterparts by morphometric and histologic
analysis. RESULTS: Successful TO was confirmed in 16 of 20 TO fetuses. Twelve of
them survived to E18.5 (75%). Fetal weights were comparable, but lung weights
were significantly greater in TO (28.41 +/- 5.87 versus 23.38 +/- 3.09, P =
0.043). Lung to body weight ratio was also greater (0.26 +/- 0.003 versus 0.22 +/
0.002, P = 0.006). E18.5 TO lungs demonstrated dilated central and distal
airspaces with increased cellularity. DNA/protein and DNA/lung weight ratios were
elevated while protein/lung weight ratio was lower in TO compared to control.
CONCLUSIONS: Mice fetal transuterine TO is feasible with comparable outcomes to
other current animal models. The increase in the lung weight, lung to body weight
ratio and the DNA/protein ratio indicate organized lung growth rather than edema
or cell hypertrophy.
PMID- 29937008
TI - Analysis of risk factors and classification of aortic fistula after
esophagectomy.
AB - BACKGROUND: Aortic fistula after esophagectomy is a rare and serious
complication. The aims of this study were to describe the causes of and classify
the fistulas. MATERIALS AND METHODS: Between January 2008 and December 2017, a
total of 1018 patients underwent esophageal resection, mainly for esophageal
cancer; aortic fistula after esophagectomy was diagnosed in four patients. We
perform a literature review through a database search for similar cases. Aortic
fistulas may be classified into two types based on the site at which they occur
in relation to the alimentary tract and area of anastomosis. Type 1 fistula
occurs within the area of anastomosis, whereas type 2 fistula occurs above or
below the anastomosis. The risk factors and clinical features associated with
aortic fistulas are described, and comparison between the two types is made.
RESULTS: Through a literature search, 39 cases were identified, of which 26 cases
were classified as type 1, and 13 cases were classified as type 2. Of 13 patients
(33.3%) who underwent emergent intervention, seven patients survived.
Approximately 76.9% of aortic fistula were related to anastomotic fistula, which
was more prevalent in type 1 aortic fistula than in type 2 (92% versus 50%, P =
0.005). There was no statistically significant difference in age, gender, side of
thoracotomy, type of anastomosis, the postoperative day the hemorrhage occurred,
warning hemorrhage, chest pain, or the outcome between the two types of fistula.
CONCLUSIONS: Anastomotic fistula is the primary cause of type 1 aortic fistula
after esophagectomy, and early diagnosis and intervention of aortic fistula can
improve prognosis. This classification may be a useful guide in determining the
approach for second-stage alimentary tract reconstruction.
PMID- 29937009
TI - Risk factors for readmission following ileal pouch-Anal anastomosis: an American
College of Surgeons National Surgical Quality Improvement Program analysis.
AB - BACKGROUND: The purpose of this study was to identify preventable reasons for
readmission and to delineate risk factors for readmission in the perioperative
period for patients with chronic ulcerative colitis undergoing ileal pouch-anal
anastomosis (IPAA). METHODS: Patients with a diagnosis of chronic ulcerative
colitis undergoing either total proctocolectomy with IPAA or proctectomy with
IPAA were identified in the American College of Surgeons National Surgical
Quality Improvement Program database from 2012-2015. Unplanned 30-d readmissions
were reviewed and categorized by reason for readmission. The unplanned
readmission rate within 30 d was calculated by the person-days method.
Multivariable Cox proportional hazard regression models determined independent
risk factors for overall 30-d unplanned readmissions and readmissions sorted by
primary readmission diagnosis. RESULTS: Three thousand four hundred one patients
had an IPAA performed during the study period. The overall unplanned readmission
rate was 32.9% per 30 person-days. Leading diagnoses for unplanned readmission
included infectious complications, dehydration, and venous thromboembolism (VTE).
Multivariable analysis found Hispanic white and black/African American
race/ethnicity (both versus non-Hispanic white) to be independently associated
with unplanned 30-d readmission. Obesity, operative time 330+ min (versus <189
min), and Hispanic white race/ethnicity (versus non-Hispanic white) were
associated with readmission for infectious complications. Age 57+ y (versus age
18-32 y) and hypertension requiring medication were associated with readmission
for dehydration. Total proctocolectomy with IPAA (versus proctectomy with IPAA)
was associated with readmission for VTE. CONCLUSIONS: One-third of patients
undergoing IPAA experience an unplanned 30-d readmission. Infectious
complications and dehydration account for most of the unplanned readmissions.
Outpatient pathways to prevent dehydration and the use of extended VTE
prophylaxis after two-stage IPAA may help reduce the rates of readmission
following IPAA.
PMID- 29937010
TI - Scholarly activity in academic plastic surgery: the gender difference.
AB - BACKGROUND: The number of women in medicine has grown rapidly in recent years.
Women constitute over 50% of medical school graduates and hold 38% of faculty
positions at United States medical schools. Despite this, gender disparities
remain prevalent in most surgical subspecialties, including plastic surgery. The
purpose of this study was to analyze gender authorship trends. MATERIALS AND
METHODS: A cross-sectional study of academic plastic surgeons was performed. Data
were collected from departmental websites and online resources. National
Institute of Health (NIH) funding was determined using the Research Portfolio
Online Reporting Tools database. Number of published articles and h-index were
obtained from Scopus (Elsevier Inc, New York, NY). Statistical analysis was
performed in SPSS (SPSS Inc, Chicago, IL). RESULTS: A total of 814 plastic
surgeons were identified in the United States. Compared to men, women had
significantly fewer years in practice (P <0.001), lower academic ranks (P
<0.001), and published less (P <0.001). There was no difference in the number of
PhD degrees between genders; women with PhDs published less than men with PhDs (P
= 0.04). 5.1% of women and 6.9% of men received NIH funding during their career
(P = 0.57). There was no gender difference in scholarly output among NIH-funded
surgeons. Overall, years in practice, academic rank, chief/program director
title, advanced degrees, and NIH funding all positively correlated with academic
productivity. CONCLUSIONS: This study identifies significant gender disparities
in scholarly productivity among plastic surgeons in academia. Future efforts
should focus on improving gender equality and eliminating barriers to academic
development.
PMID- 29937011
TI - Reducing road traffic deaths: where should we focus global health initiatives?
AB - BACKGROUND: Current global surgery initiatives focus on increasing surgical
workforce; however, it is unclear whether this approach would be helpful
globally, as patients in low-resource countries may not be able to reach
hospitals in a timely fashion without formal Emergency Medical Services (EMS). We
hypothesize that increased surgical workforce correlates with decreased road
traffic deaths (RTDs) only in countries with EMS. METHODS: Estimated RTDs were
obtained from the Global Status Report on Road Safety 2013, which estimated the
RTD rate in 2010 (RTD 2010). The classification of EMS was defined by the Global
Status Report on Road Safety 2009. The density of surgeons, anesthesiologists,
and obstetricians (SAO density) and 2010 income classification were accessed from
the World Bank. Multivariable regression analysis was performed adjusting for
different countries, income levels, and trauma system characteristics.
Sensitivity analysis was performed. RESULTS: One-fourth of the countries reported
not having formal EMS (n = 41, 23.4%). On adjusted analysis, SAO density was not
associated with changes in RTD 2010 in countries without EMS (n = 25, P = 0.50).
However, in countries with EMS, each increase in SAO density per 100,000
population decreased RTDs by 0.079 per 100,000 population (n = 97, P <0.001).
Income was the only other factor resulting in reduced mortality rates (P =
0.004). Sensitivity analysis confirmed these findings. CONCLUSIONS: Increases in
surgical workforce reduce RTDs only when EMS exist. Surgical workforce and EMS
must be seen as part of the same system and developed together to maximize their
effect in reducing RTDs. Global health initiatives should be tailored to
individual country need. LEVEL OF EVIDENCE: Level II (Ecological study).
PMID- 29937012
TI - Clinical factors and high-resolution manometry predicting response to surgery for
achalasia in children.
AB - BACKGROUND: Esophageal achalasia is an uncommon condition in children. Although
many interventions exist for the management of this disorder, esophageal (Heller)
myotomy offers one of the most durable treatments. Our institution sought to
review patients undergoing Heller myotomy concentrating on preoperative clinical
factors that might predict postoperative outcomes. MATERIALS AND METHODS: All
patients from January 1, 2007, to December 31, 2016, who underwent surgical
treatment for achalasia at our tertiary pediatric hospital were identified and
included in the study cohort. Electronic medical records for these patients were
reviewed for clinical presentation variables, nonsurgical preoperative treatment,
surgical approach, clinical response to surgery, need for postoperative treatment
for ongoing symptoms, and high-resolution manometry (HRM) data. RESULTS: Twenty
six patients were included in the study, and all underwent myotomy with partial
fundoplication (median age: 14.4 y [interquartile range 11.6-15.5]). At a median
follow-up of 9.75 mo (interquartile range 3.5-21 mo), 16 (61.5%) patients
reported good resolution of their dysphagia symptoms with surgery alone. Two
patients (7.7%) had perforation of the gastrointestinal tract requiring surgical
intervention. Eight patients (30.8%) required additional treatment for achalasia,
with 5 (19.2%) of these undergoing additional surgery or endoscopic treatment.
Patients who had preoperative dilation did not have good resolution of their
dysphagia (n = 2; P = 0.037). Two of four patients undergoing postoperative
dilation had preoperative dilation. None of these patients underwent preoperative
manometry. There was a statistically significant difference in the ages of
patients who required postoperative intervention and those who did not (14.1
versus 15.2 y old, respectively; P = 0.043). In patients who reported improvement
of gastroesophageal reflux disease/reflux type symptoms after Heller myotomy,
lower esophageal residual pressure (29.1 versus 18.7 mmHg; P = 0.018) on
preoperative HRM was significantly higher than in those who did not report
improvement after surgery. Higher upper esophageal mean pressure (66.6 versus
47.8 mmHg; P = 0.05) also predicted good gastroesophageal reflux disease/reflux
symptom response in a similar manner. CONCLUSIONS: Current analysis suggests that
preoperative dilation should be used cautiously and older patients may have a
better response to surgery without need for postoperative treatment. In addition,
preoperative HRM can aid in counseling patients in the risk of ongoing symptoms
after surgery and may aid in determining if a fundoplication should be completed
at the index procedure. Further research is needed to delineate these factors.
LEVEL OF EVIDENCE: Level III.
PMID- 29937013
TI - Is less more? Laparoscopic versus open Ladd's procedure in children with
malrotation.
AB - BACKGROUND: With the advent of minimally invasive techniques, laparoscopic Ladd's
procedure is increasingly used to treat children with malrotation, yet evidence
regarding its safety and efficacy is lacking. We hypothesize that operative and
postoperative outcomes with the open technique are superior to the laparoscopic
Ladd's procedure. METHODS: We conducted a 5-y retrospective chart review of all
patients who underwent Ladd's procedure at our institution from 2010-2015.
Exclusion of patients included those with concomitant conditions, such as poor
gut perfusion, significant reflux, tracheoesophageal fistula, failure to thrive
requiring concomitant gastrostomy, and biliary atresia. Kruskal-Wallis and Mann
Whitney tests were used where appropriate. RESULTS: Between 2010 and 2015, of 130
patients who underwent Ladd's procedure, 77 met inclusion criteria. Sixty-two
patients underwent initial open surgery, 15 patients underwent laparoscopy, seven
of which were converted to open. Patients undergoing open surgery were younger
compared to the laparoscopic groups. Thirty-three of the 77 malrotation patients
(43%) presented with volvulus, 27 underwent open surgery, four had laparoscopic
converted to open procedures, and two patients underwent laparoscopic Ladd's
without incident. Laparoscopy resulted in increased operative time and clinic
visits. Patients undergoing laparoscopic to open surgery had longer operative
times, time to resume diet, and length of hospital stay. No difference was noted
in complications among the groups. CONCLUSIONS: Although minimally invasive
approaches are becoming increasingly used, no evidence supports laparoscopic
superiority over open Ladd's procedure. We found that open surgery was associated
with shorter operating times and fewer clinic visits. Furthermore, laparotomy
remains the favored procedure for patients presenting with volvulus.
PMID- 29937014
TI - Assessment of the predictive value of the International Classification of
Diseases Injury Severity Score for trauma mortality in urban India.
AB - BACKGROUND: Trauma is the cause of 1.2 million deaths in India annually. Injury
severity scores play an important role in trauma research and care because these
scores enable the adjustment of trauma severity when comparing mortality
outcomes. The generalizability of the International Classification of Diseases
Injury Severity Score (ICISS) between different populations is not fully known,
and the validity of the ICISS has not been assessed in the Indian context. The
aim of this study was to assess the predictive performances of three
international versions of the ICISS, derived from data from Australia, New
Zealand and pooled data from seven different high-income countries, in trauma
patients admitted to four public hospitals in urban India. MATERIAL AND METHODS:
We used patient data from an Indian cohort of 16,047 trauma patients. The
patients were assigned an ICISS based on International Classification of Diseases
codes using survival risk ratios from publicly available data sets from Australia
and New Zealand and with pooled data from seven different high-income countries.
Predicted mortality based on the ICISS was compared with observed patient
mortality, and the predictive performance was assessed in terms of discrimination
and calibration. RESULTS: Discrimination and calibration did not reach the
threshold for predictive performance in any of the ICISS versions used. The
threshold value used was 0.8 for discrimination, which was not significantly
different from one for the calibration slope and not significantly different from
zero for the calibration intercept. CONCLUSIONS: None of the international
versions of the ICISS adequately predicted mortality within the study population,
indicating the need for an ICISS version specifically adapted to the Indian
context.
PMID- 29937015
TI - A systematic review of outcomes reported in small bowel obstruction research.
AB - BACKGROUND: Small bowel obstruction (SBO) is a condition which is commonly
treated by general surgeons. The evidence base for treatment of this condition is
limited in part by variable reporting of outcomes in the literature. The aim of
this study was to identify commonly used outcomes in research on SBO. METHODS:
This review was reported in line with Preferred Reporting Items for Systematic
Reviews and Meta-Analyses guidelines and registered with PROSPERO
(CRD42017065538). Searches were performed of MEDLINE, Embase, and Cochrane
Central Register of Controlled Trials databases to identify prospective cohort or
randomized trials reporting outcomes of interventions in SBO. Studies addressing
diagnostics, pediatric populations, and SBO due to malignancy were excluded.
Studies were screened for inclusion. Study and outcome characteristics were
extracted into a -predesigned pro forma and mapped onto the Outcome Measures in
Rheumatology (OMERACT) framework. RESULTS: A total of 1222 studies were screened
for eligibility, 74 full text articles retrieved, and 51 studies included for
synthesis. A total of 50 different outcomes were used. Duration of hospital stay
was the most frequently reported outcome (n = 21 studies). Resolution of SBO was
reported in 12 studies but only defined in eight studies which used six different
definitions. Patient-reported outcomes were reported in only four studies.
CONCLUSIONS: There is a high degree of variation in the outcomes reported in SBO
research. There is a clear need for a core outcome set. Development of a patient
reported outcome measure for this condition should also be explored.
PMID- 29937016
TI - The impact of individual physicians on outcomes after trauma: is it the system or
the surgeon?
AB - BACKGROUND: Benchmarking of mortality outcomes across the country has revealed
major differences in survival based on the trauma center at which a patient
receives care. The role of the individual surgeon in determining trauma outcomes
is unknown. Most believe that differences in outcomes are primarily driven by
system- and process-based variations. Our objective was to determine if variation
in individual surgeon outcomes could help explain difference in survival after
trauma. METHODS: Analysis of trauma patients in the Florida State Inpatient
Database from 2010 to 2014. The presence of unique physician identifiers, in
addition to hospital identifiers, rendered this data set ideal for performance of
multilevel analysis. The amount of the variation attributable to surgeon-level
variation was calculated using multilevel random-effects models controlling for
patient clinical factors (such as injury severity and comorbidities/age) and
hospital-level factors, such as case mix and bed size. RESULTS: There were 31
hospitals, 175 surgeons, and 65,706 admissions. The overall mortality rate was
5.6%. The average mortality rate across surgeons ranged from 0% to 17.4% (mean
0.4%, standard deviation 1.85). At the individual surgeon level, when controlling
for clinical and hospital-level factors, 9% of this variation was attributable
solely to the surgeon. CONCLUSIONS: At the state level, we found that differences
in outcomes among trauma centers are impacted by individual surgeon-level
variation. Implementation of protocolized, system-based trauma care is useful for
improving the overall quality of care for injured patients but does not entirely
negate surgeon-specific variations in management.
PMID- 29937017
TI - Postoperative surgical trainee opioid prescribing practices (POST OPP): an
institutional study.
AB - BACKGROUND: Increasing mortality from opioid overdoses has prompted increased
focus on prescribing practices of physicians. Unfortunately, resident physicians
rarely receive formal education in effective opioid prescribing practices or
postoperative pain management. Data to inform surgical training programs
regarding the utility and feasibility of formal training are lacking. METHODS:
Following Institutional Review Board approval, a single institution's resident
physicians who had completed at least one surgical rotation were surveyed to
assess knowledge of pain management and evaluate opioid prescribing practices.
RESULTS: Fifty-three respondents (68% males and 32% females) completed the
survey. Most respondents denied receiving formal instruction in opioid pain
medication prescribing practices during either medical school (62.3%) or
residency (56.6%); however, nearly all respondents stated they were aware of the
side effects of opioid pain medications, and a majority felt confident in their
knowledge of opioid pharmacokinetics and pharmacodynamics. Of the respondents,
47% either "agreed" or "strongly agreed" that they prescribed more opioid
medications than necessary to patients being discharged following a surgical
procedure. Individual case scenario responses demonstrated variability in the
number of morphine milligram equivalents prescribed across scenarios (P < 0.001).
Male and nonsurgical specialty respondents reported prescribing significantly
fewer overall morphine milligram equivalents in these scenarios. CONCLUSIONS:
This pilot study shows wide variability in opioid prescribing practices and
attitudes toward pain management among surgical trainees, illustrating the
potential utility of formal education in pain management and effective
prescribing of these medications. A broader assessment of surgical trainees'
knowledge and perception of opioid prescribing practices is warranted to
facilitate the development of such a program.
PMID- 29937018
TI - Impact and treatment success of new-onset atrial fibrillation with rapid
ventricular rate development in the surgical intensive care unit.
AB - BACKGROUND: Atrial fibrillation (AF) with rapid ventricular rate (RVR; heart rate
>100) in noncardiac postoperative surgical patients is associated with poor
outcomes. The objective of this study was to evaluate the practice patterns of AF
management in a surgical intensive care unit to determine practices associated
with rate and rhythm control and additional outcomes. MATERIALS AND METHODS:
Adult patients (>=18 y) admitted to the surgical intensive care unit (SICU) from
June 2014 to June 2015 were retrospectively screened for the development of new
onset AF with RVR. Demographics, hospital course, evaluation and treatment of AF
with RVR, and outcome were evaluated and analyzed. RESULTS: Thousand seventy
patients were admitted to the SICU during the study period; 33 met inclusion
criteria (3.1%). Twenty-six patients (79%) had rate and rhythm control within 48
h of AF with RVR onset. beta-Blockers were the most commonly used initial
medication (67%) but were successful at rate and rhythm control in only 27% of
patients (6/22). Amiodarone had the highest rate of success if used initially
(5/6, 83%) and secondarily (11/13, 85%). Failure to control rate and rhythm was
associated with a greater likelihood of comorbidities (100% versus 57%; P =
0.06). CONCLUSIONS: New-onset AF with RVR in the noncardiac postoperative patient
is associated with a high mortality (21%). Amiodarone is the most effective
treatment for rate and rhythm control. Failure to establish rate and rhythm
control was associated with cardiac comorbidities. These results will help to
form future algorithms for the treatment of AF with RVR in the SICU.
PMID- 29937019
TI - Can ultrasound reliably identify complicated appendicitis in children?
AB - BACKGROUND: The ability of ultrasound to identify specific features relevant to
nonoperative management of pediatric appendicitis, such as the presence of
complicated appendicitis (CA) or an appendicolith, is unknown. Our objective was
to determine the reliability of ultrasound in identifying these features.
METHODS: We performed a retrospective study of children who underwent
appendectomy after an ultrasound at four children's hospitals. Imaging,
operative, and pathology reports were reviewed. Sensitivity, specificity,
positive predictive value (PPV), and negative predictive value (NPV) of
ultrasound for identifying CA based on pathology and intraoperative findings and
an appendicolith based on pathology were calculated. CA was defined as a
perforation of the appendix. Equivocal ultrasounds were considered as not
indicating CA. RESULTS: Of 1027 patients, 77.5% had simple appendicitis, 16.2%
had CA, 5.4% had no evidence of appendicitis, and 15.6% had an appendicolith.
Sensitivity and specificity of ultrasound for detecting CA based on pathology
were 42.2% and 90.4%; the PPV and NPV were 45.8% and 89.0%, respectively.
Sensitivity and specificity of ultrasound for detecting CA based on
intraoperative findings were 37.3% and 92.7%; the PPV and NPV were 63.4% and
81.4%, respectively. Sensitivity and specificity of ultrasound for detecting an
appendicolith based on pathology were 58.1% and 78.3%; the PPV and NPV were 33.1%
and 91.0%, respectively. Results were similar when equivocal ultrasound and
negative appendectomies were excluded. CONCLUSIONS: The high specificity and NPV
suggest that ultrasound is a reliable test to exclude CA and an appendicolith in
patients being considered for nonoperative management of simple appendicitis.
PMID- 29937020
TI - Structured box training improves stability of retraction while multitasking in
colorectal surgery simulation.
AB - BACKGROUND: Laparoscopic colorectal surgery has an established role. The ability
to multitask (use a retraction tool with one hand and navigate a laparoscopic
camera with the other) is desired for efficient laparoscopic surgery. Surgical
trainees must learn this skill to perform advanced laparoscopic tasks. The aim
was to determine whether a box-training protocol improves the stability of
retraction while multitasking in colorectal surgery simulation. MATERIALS AND
METHODS: Fifty-eight medical students were recruited to attend a basic
laparoscopic box-training course. Ability to perform steady retraction with and
without multitasking was measured initially and at the conclusion of the course.
RESULTS: Before training, students demonstrated a decrease in performance while
multitasking with a greater maximal exerted force, a greater range of force, and
a greater standard deviation for traction and minimal exerted force, range of
force and a greater standard deviation for countertraction. Statistically
significant improvement (lower maximal exerted force and lower range of force)
was observed for traction while multitasking after training. After the training,
no statistically significant differences were found when the student performed a
single task versus multitasking, both for traction and countertraction.
CONCLUSIONS: A structured box-training curriculum improved the stability of
retraction while multitasking in this colorectal surgery simulation. Although it
did not improve stability of retraction as a single task, it did improve
stability of retraction while multitasking. After training, this enables the
trainee to retract as efficiently while operating the camera as they retract when
only focusing on retraction as a single task.
PMID- 29937021
TI - Postoperative outcomes of esophagectomy for cancer in elderly patients.
AB - BACKGROUND: The number of elderly patients with esophageal cancer is expected to
increase. We aimed to determine the postoperative outcomes of esophagectomy for
esophageal cancer in elderly patients. MATERIAL AND METHODS: A retrospective,
population-based analysis was performed using the National inpatient sample for
the period 2000-2014. Adult patients >=18 years old (yo) diagnosed with
esophageal cancer who underwent esophagectomy during their inpatient
hospitalization were included. Patients were categorized into <70 yo and >=70 yo.
Multivariable linear and logistic regressions were used to assess the potential
effect of age on postoperative complications, inpatient mortality, and hospital
charges. RESULTS: Overall, 5243 patients were included, with 3699 (70.6%) <70 yo
and 1544 (29.5%) >=70 yo. The yearly rate of esophagectomies among patients >=70
yo did not significantly changed during the study period (28.4% in 2000 and 26.3%
in 2014, P = 0.76). Elderly patients were significantly more likely to have
postoperative cardiac failure (odds ratio 1.59, 95% confidence interval [CI]
1.21, 2.09, P = 0.0009) and inpatient mortality (odds ratio 1.84, 95% CI 1.39,
2.45, P < 0.0001). Among the elderly patients, hospital charges were, on average,
$16,320 greater (95% CI $3110, $29,530) than patients <70 yo (P = 0.02). The
predicted probability of mortality increased consistently across age (1.5% in 40
yo, 2.5% in 50 yo, 3.6% in 60 yo, 5.4% in 70 yo, and 7.0% in 80 yo). CONCLUSIONS:
Elderly patients undergoing esophagectomy for cancer have a significantly higher
risk of postoperative mortality and pose a higher financial burden on the health
care system. Elderly patients with esophageal cancer should be carefully selected
for surgery.
PMID- 29937022
TI - Using Bradford's law of scattering to identify the core journals of pediatric
surgery.
AB - BACKGROUND: Bradford's law of scattering defines an exponentially diminishing
return when extending a search for references in journals and can be used to
identify the "core" journals in a field. The purpose of this study was to
identify the core journals of pediatric surgery. METHODS: With Institutional
Review Board approval, we developed bibliometric profiles for the top
academically productive pediatric surgeons in the United States. These profiles
included the total number of publications, journals in which those authors
published their manuscripts, and identification of all articles cited by those
surgeons, along with the journals those references were drawn from. Bradford's
law of scattering was applied to identify the core journals of pediatric surgery.
RESULTS: We identified n = 69 pediatric surgeons (10 +/- 0.2 5-year h-index).
These authors published 10,031 articles (145 +/- 90 per surgeon), which were
cited 250841 times (3635 +/- 413 per surgeon). Pediatric surgeons' articles
contained 199507 references (2891 +/- 176 per surgeon). We analyzed 58,310
references (top 20 journals) cited by pediatric surgeons. Bradford's Law
identified a single core journal for p = 3-10 zones, with P = 3, providing the
best correlation between predicted and actual values (R^2 = 0.9996). The core
journal for pediatric surgery is Journal of Pediatric Surgery. CONCLUSIONS: We
used Bradford's Law to identify the core journals of pediatric surgery. These
core journals include the two leading pediatric surgery-specific journals and the
highest impact factor journals in surgery (Annals of Surgery) and medicine
(NEJM). These findings can help busy pediatric surgeons focus their reading to
stay updated in a rapidly evolving field.
PMID- 29937023
TI - Outpatient curettage and electrocautery as an alternative to primary surgical
closure for pediatric gastrocutaneous fistulae.
AB - BACKGROUND: The development of a gastrocutaneous fistula (GCF) after gastrostomy
tube removal is a frequent complication that occurs 5%-45% of the time.
Conservative therapy with chemical cauterization is frequently unsuccessful, and
surgical GCF repair with open primary layered closure of the gastrotomy is often
required. We describe an alternative approach of GCF closure that is an
outpatient, less invasive procedure that allows patients to avoid the
comorbidities of general endotracheal anesthesia and intraabdominal surgery.
METHODS: This is an Institutional Review Board approved retrospective review of
all patients who underwent GCF closure from January 2010 to July 2016 at a
tertiary care children's hospital. Demographics including age, weight, body mass
index, comorbidities, and initial indication for gastrostomy tube were recorded.
Operative details such as ASA score, operative duration, type of anesthesia, and
airway were noted. Based on surgeon preference, two types of operative closure
were used during that time frame: primary layered closure or curettage and
cautery (C&C). The latter is a procedure in which the fistula tract is first
scraped with a fine curette, and then the fistula opening and tract are
cauterized circumferentially. Finally, the presence of a persistent fistula and
the need for formal reoperation were determined. RESULTS: Sixty-five unique
patients requiring GCF closure were identified. Of those, 44 patients (67.6%)
underwent primary closure and 21 patients (32.3%) underwent C&C. The success rate
of primary closure was 97% with one patient experiencing wound breakdown with
persistent fistula. The overall success rate of C&C was 66.7% (14/21). Among
those 14 patients, 11 (52.4%) GCF patients were closed by 1 mo. An additional two
patients' gastrocutaneous fistulae were closed by 4 mo (61.9%). One GCF was
successfully closed with a second C&C procedure. Seven of the 21 patients (33.3%)
required subsequent formal layered surgical closure. C&C had significantly
shorter operative times (13.5 +/- 14.7 min versus 93.4 +/- 61.8, P <0.0001) and
significantly shorter times in the postanesthesia care unit (101.8 +/- 42.4 min
versus 147 +/- 86, P <0.0001). Patients were intubated with an endotracheal tube
88.6% of the time for primary closure and 23.8% of the time for C&C.Among
patients admitted for an elective procedure, the average length of stay for
primary closure was 1.9 d as compared to 0 d for the C&C group. Among patients
who underwent C&C with a persistent fistula, there were no significant
differences in time since initial creation of gastrostomy, age, body mass index,
or ASA score. CONCLUSIONS: Our study verifies that primary closure remains the
gold standard for persistent GCF. However, C&C is a safe, outpatient procedure
that effectively treats a GCF the majority of the time in children. We suggest
that in select patients, it may be an appropriate initial and definitive
procedure for GCF closure.
PMID- 29937024
TI - The Cost of Putting Fistula First.
PMID- 29937025
TI - Erratum Regarding "Hemodialysis Self-management Intervention Randomised Trial
(HED-SMART): A Practical Low-Intensity Intervention to Improve Adherence and
Clinical Markers in Patients Receiving Hemodialysis" (Am J Kidney Dis.
2018;71[3]:371-381).
PMID- 29937026
TI - Are County Codes More Indicative of Kidney Health Than Genetic Codes?
PMID- 29937027
TI - Hypercalcemia, Acute Kidney Injury, and Esophageal Lymphadenopathy.
PMID- 29937028
TI - The Society for Vascular Surgery practice guidelines on follow-up after vascular
surgery arterial procedures.
PMID- 29937029
TI - Invited commentary.
PMID- 29937030
TI - Invited commentary.
PMID- 29937031
TI - Invited commentary.
PMID- 29937032
TI - Hybrid repair of multiple subclavian and axillary artery aneurysms in a patient
with Marfan syndrome.
PMID- 29937033
TI - The Society for Vascular Surgery practice guidelines on follow-up after vascular
surgery arterial procedures.
AB - Although follow-up after open surgical and endovascular procedures is generally
regarded as an important part of the care provided by vascular surgeons, there
are no detailed or comprehensive guidelines that specify the optimal approaches
with regard to testing methods, indications for reintervention, and follow-up
intervals. To provide guidance to the vascular surgeon, the Clinical Practice
Council of the Society for Vascular Surgery appointed an expert panel and a
methodologist to review the current clinical evidence and to develop
recommendations for follow-up after vascular surgery procedures. For those
procedures for which high-quality evidence was not available, recommendations
were based on observational studies, committee consensus, and indirect evidence.
Recognizing that there are numerous published reports on the role of duplex
ultrasound for surveillance of infrainguinal vein bypass grafts, the Society
commissioned a systematic review and meta-analysis on this topic. The panel
classified the strength of each recommendation and the corresponding quality of
evidence on the basis of the Grading of Recommendations Assessment, Development,
and Evaluation (GRADE) system: recommendations were graded either strong or weak,
and the quality of evidence was graded high, moderate, or low. The resulting
recommendations represent a wide variety of open surgical and endovascular
procedures involving the extracranial carotid artery, thoracic and abdominal
aorta, mesenteric and renal arteries, and lower extremity arterial
revascularization. The panel also identified many areas in which there was a lack
of high-quality evidence to support their recommendations. This suggests that
there are opportunities for further clinical research on testing methods,
threshold criteria, and the role of surveillance as well as on the modes of
failure and indications for reintervention after vascular surgery procedures.
PMID- 29937034
TI - A systematic review and meta-analysis of one-stage versus two-stage
brachiobasilic arteriovenous fistula creation.
AB - BACKGROUND: Long-term patency of arteriovenous fistulas (AVFs) is critical for
hemodialysis vascular access. We compared the efficacy of a one-stage vs two
stage approach to brachiobasilic AVF creation by primarily investigating primary
and secondary patency rates. We hypothesize that the two-stage is superior to the
one-stage procedure in terms of efficacy and safety. METHODS: This review was
performed as per the Preferred Reporting Items for Systematic Reviews and Meta
Analysis guidelines. Searches were performed on MEDLINE, EMBASE, Google Scholar,
and Cochrane Database. Risk of bias and quality assessment scores were both
performed based on previously validated tool. RESULTS: The systematic search
revealed a total of 242 publications for possible inclusion. On the basis of
title and abstract review, two randomized controlled trials and nine case-cohort
series fit our inclusion criteria. There were no statistically significant
differences in failure rates (pooled risk ratio [RR], 1.10; 95% confidence
interval [CI], 0.79-1.55; P = .25), 1-year primary patency rates (RR, 1.31; 95%
CI, 0.83-2.06; P = .24), 1-year secondary patency rates (RR, 0.97; 95% CI, 0.54
1.77) and 2-year secondary patency rates (RR, 1.19; 95% CI, 0.54-2.63; P = .67)
between both groups. However, the two-stage procedure had significantly improved
2-year primary patency rates (RR, 2.50; 95% CI, 1.66-3.74; P < .00001). There
were no differences in steal syndrome, hematoma, infection, pseudoaneuryms, or
stenosis, although there was a trend toward an increased incidence of
postoperative thrombosis (RR, 1.81; 95% CI, 0.95-3.45; P = .07) in one-stage
procedures. CONCLUSIONS: With improved 2-year primary patency rates and the
absence of significant differences in complications, this study suggests
potential benefit of a two-stage over a one-stage procedure for brachiobasilic
AVF creation. However, rather than being a definitive answer, our results merely
highlight the continuing need for an adequately powered, well-designed,
randomized controlled trial to interrogate this question further.
PMID- 29937035
TI - Use and impact of patient relationship modifiers on cost measurement.
PMID- 29937036
TI - Regarding "A novel technique for duplex-guided office-based interventions for
patients with acute arteriovenous fistula occlusion".
PMID- 29937037
TI - Reply.
PMID- 29937038
TI - Regarding "Retroperitoneoscopic lumbar sympathectomy for plantar hyperhidrosis".
PMID- 29937039
TI - Reply.
PMID- 29937040
TI - Invited commentary.
PMID- 29937041
TI - Invited commentary.
PMID- 29937042
TI - Making Mistakes Empowers Cancer Cells.
AB - Lethal cancers have genomes that can reflect a jigsaw puzzle put together in a
hurricane. The missing, misjoined, and extra pieces contribute to the driving
forces behind the cancer phenotypes. But is this the only reason genomic
instability is so prevalent in aggressive cancers? New findings support that the
hurricane winds themselves, not just their aftermath, contribute to the cancer
phenotype of metastasis.
PMID- 29937043
TI - Mining Public Databases for Precision Oncology.
AB - Millions of dollars have been spent on creating public databases. To date these
data reside in isolated 'silos'. Real-world realization of precision oncology,
the right drug for the right patient at the right time, may be possible only if
the right data come to the right clinic at the right time.
PMID- 29937044
TI - MicroRNAs Regulating MicroRNAs in Cancer.
AB - MicroRNAs (miRNA) are capable of self-regulation, termed miRNA to miRNA
interaction. Very little is known about these interactions and their impact on
the cellular milieu. We discuss known miRNA to miRNA interactions, potential
mechanisms, and their role in cancer.
PMID- 29937045
TI - The Value of Outbred Rodent Models in Cancer Research.
AB - Mouse models of breast cancer are valuable research tools, but their usefulness
is restricted by a series of features inherent to their physiology, such as low
endogenous estrogens and genetics (inbred status). Depending on the specific
questions asked, outbred rodents like Peromyscus may provide answers that
laboratory mice cannot.
PMID- 29937046
TI - Tracing Renal Cell Carcinomas back to the Nephron.
AB - Renal cell carcinomas (RCCs) are a heterogeneous group of tumors derived from the
epithelial cells of the nephron. In recent years the genetic landscape of these
tumors has been detailed, leading to progress in mouse modeling of the human
disease. In parallel, substantial advancements have been made in describing the
transcriptional programs of normal nephron cell types and how they respond to
renal insults. Integrating these research fields may provide a deeper
understanding of renal tumor initiation and progression, and provide leads that
can be conveyed into mouse models that faithfully recapitulate the different RCC
subtypes. We summarize here the genetic lesions and molecular pathways that
define RCC subtypes and discuss how these relate to cell-of-origin and renal
repair programs.
PMID- 29937047
TI - Cancer Progression Goes Viral: The Role of Oncoviruses in Aggressiveness of
Malignancies.
AB - Cancer progression is the most relevant phase of carcinogenesis due to the
development of malignant tumors in the host. Some viruses participate in
malignant cell transformation, with recent compelling evidence suggesting that
oncoviruses also have a role in cancer progression. The human hepatitis B (HBV)
and C (HCV) viruses, human papillomaviruses (HPV), Epstein-Barr virus (EBV), and
Kaposi sarcoma herpesvirus (KSHV) are the most important human oncoviruses
currently known. Here, we discuss how oncoviruses can modulate cancer
progression, such as tumor growth, invasion, and cancer metastasis.
PMID- 29937048
TI - Applications of CRISPR-Cas Enzymes in Cancer Therapeutics and Detection.
AB - Cancer is a complex disease caused by combinations of cellular genetic
alterations and heterogeneous microenvironments. The use of the robust and
programmable CRISPR-Cas systems has greatly improved genome editing for precision
cancer modeling and enabled multiplexed genetic manipulation for cancer treatment
and mutation detection. In this review, we outline the current CRISPR-Cas
toolkit, and discuss the promises and hurdles in translating this revolutionary
technology into effective and safe clinical applications for cancer treatment and
diagnosis.
PMID- 29937049
TI - Efficacy of Therapies for Postural Tachycardia Syndrome: A Systematic Review and
Meta-analysis.
AB - OBJECTIVE: To identify the evidence base and evaluate the efficacy of each
treatment for postural tachycardia syndrome (POTS) in light of a recent consensus
statement highlighting the lack of treatment options with clear benefit to risk
ratios for this debilitating condition. METHODS: The CENTRAL (Cochrane Central
Register of Controlled Trials), PubMed, and Embase databases from inception to
May 2017 were searched using the terms postural AND tachycardia AND syndrome. A
total of 135 full-text publications were screened after excluding duplicates
(n=681), conference abstracts (n=467), and records that did not relate to POTS
therapy (n=876). We included 28 studies with at least 4 patients with POTS in
which symptomatic response was reported after more than 4 weeks of therapy. This
review was performed according to the PRISMA (Preferred Reporting Items for
Systematic Reviews and Meta-Analyses) statement. Two investigators independently
performed the data extraction and evaluated the quality of evidence. RESULTS:
This study comprised 25 case series and 3 small randomized controlled trials that
evaluated 755 and 103 patients with POTS, respectively. Interventions directed at
increasing intravascular volume, increasing peripheral or splanchnic vascular
tone, controlling heart rate, and increasing exercise tolerance demonstrate
moderate efficacy (range, 51%-72%). Few data exist on their comparative
effectiveness. Significant heterogeneities were seen in terms of patient age,
symptom severity, and the measures used to evaluate treatment efficacy.
CONCLUSION: The current evidence base to guide optimal management of patients
with POTS is extremely limited. More high-quality collaborative research with
standardized reporting of symptom response and treatment tolerability is urgently
needed.
PMID- 29937050
TI - The Vascularised Chamber as an In Vivo Bioreactor.
AB - Vascularisation is key to developing large transplantable tissue constructs
capable of providing therapeutic benefits. The vascularised tissue engineering
chamber originates from surgical concepts in tissue prefabrication and
microsurgery. It serves as an in vivo bioreactor in the form of a closed,
protected space surgically created and embedded within the body by fitting a
noncollapsible chamber around major blood vessels. This creates a highly
angiogenic environment which facilitates the engraftment and survival of
transplanted cells and tissue constructs. This article outlines the chamber
concept and explores its application in the context of recent advances in
biomedical engineering, and how this can play a role in the future of cell
therapies and regenerative medicine.
PMID- 29937051
TI - CRISPR-Based Technologies for Metabolic Engineering in Cyanobacteria.
AB - In metabolic engineering, the production of industrially relevant chemicals, via
rational engineering of microorganisms, is an intensive area of research. One
particular group of microorganisms that is fast becoming recognized for their
commercial potential is cyanobacteria. Through the process of photosynthesis,
cyanobacteria can use CO2 as a building block to synthesize carbon-based
chemicals. In recent years, clustered regularly interspaced short palindromic
repeats (CRISPR)-dependent approaches have rapidly gained popularity for
engineering cyanobacteria. Such approaches permit markerless genome editing,
simultaneous manipulation of multiple genes, and transcriptional regulation of
genes. The drastically shortened timescale for mutant selection and segregation
is especially advantageous for cyanobacterial work. In this review, we highlight
studies that have implemented CRISPR-based tools for the metabolic engineering of
cyanobacteria.
PMID- 29937052
TI - Polyphasic characterization of four soil-derived phenanthrene-degrading
Acidovorax strains and proposal of Acidovorax carolinensis sp. nov.
AB - Four bacterial strains identified as members of the Acidovorax genus were
isolated from two geographically distinct but similarly contaminated soils in
North Carolina, USA, characterized, and their genomes sequenced. Their 16S rRNA
genes were highly similar to those previously recovered during stable-isotope
probing (SIP) of one of the soils with the polycyclic aromatic hydrocarbon (PAH)
phenanthrene. Heterotrophic growth of all strains occurred with a number of
organic acids, as well as phenanthrene, but no other tested PAHs. Optimal growth
occurred aerobically under mesophilic temperature, neutral pH, and low salinity
conditions. Predominant fatty acids were C16:1omega7c/C16:1omega6c, C16:0, and
C18:1omega7c, and were consistent with the genus. Genomic G+C contents ranged
from 63.6 to 64.2%. A combination of whole genome comparisons and physiological
analyses indicated that these four strains likely represent a single species
within the Acidovorax genus. Chromosomal genes for phenanthrene degradation to
phthalate were nearly identical to highly conserved regions in phenanthrene
degrading Delftia, Burkholderia, Alcaligenes, and Massilia species in regions
flanked by transposable or extrachromosomal elements. The lower degradation
pathway for phenanthrene metabolism was inferred by comparisons to described
genes and proteins. The novel species Acidovorax carolinensis sp. nov. is
proposed, comprising the four strains described in this study with strain NA3T as
the type strain (=LMG 30136, =DSM 105008).
PMID- 29937053
TI - The Value Proposition of Academy Membership.
PMID- 29937054
TI - Changes in the National Diabetes Prevention Program Present Opportunities for
Registered Dietitian Nutritionists to Reduce the Prevalence of Diabetes.
PMID- 29937056
TI - Erratum.
PMID- 29937055
TI - Position of the Academy of Nutrition and Dietetics: Benchmarks for Nutrition in
Child Care.
AB - It is the position of the Academy of Nutrition and Dietetics that early care and
education (ECE) programs should achieve recommended benchmarks to meet children's
nutrition needs and promote children's optimal growth in safe and healthy
environments. Children's dietary intake is influenced by a number of factors
within ECE, including the nutritional quality of the foods and beverages served,
the mealtime environments, and the interactions that take place between children
and their care providers. Other important and related health behaviors that may
influence the development of obesity include children's physical activity, sleep,
and stress within child care. Recent efforts to promote healthy eating and
improve other health behaviors in ECE include national, state, and local policy
changes. In addition, a number of interventions have been developed in recent
years to encourage healthy eating and help prevent obesity in young children in
ECE. Members of the dietetics profession, including registered dietitian
nutritionists and nutrition and dietetics technicians, registered, can work in
partnership with ECE providers and parents to help promote healthy eating,
increase physical activity, and address other important health behaviors of
children in care. Providers and parents can serve as role models to support these
healthy behaviors. This Position Paper presents current evidence and
recommendations for nutrition in ECE and provides guidance for registered
dietitian nutritionists; nutrition and dietetics technicians, registered; and
other food and nutrition practitioners working with parents and child-care
providers. This Position Paper targets children ages 2 to 5 years attending ECE
programs and highlights opportunities to improve and enhance children's healthy
eating while in care.
PMID- 29937057
TI - What Is a National Provider Identifier and Why Does Every Dietetics Practitioner
Need One?
PMID- 29937059
TI - Synthesis and antibacterial activity of novel ketolides with 11,12-quinoylalkyl
side chains.
AB - A series of quinoylalkyl side chains was designed and synthesized, followed by
introduction into ketolides by coupling with building block 6 or 32. The
corresponding targets 7a-n, 33b, and 33e were tested for their in vitro
activities against a series of macrolide-sensitive and macrolide-resistant
pathogens. Some of them showed a similar antibacterial spectrum and comparable
activity to telithromycin. Among them, two C2-F ketolides, compounds 33b and 33e,
displayed excellent activities against macrolide-sensitive and macrolide
resistant pathogens.
PMID- 29937058
TI - Exploration of diphenylalkyloxadiazoles as novel cardiac myosin activator.
AB - To explore novel cardiac myosin activator, a series of diphenylalkyl substituted
1,3,4-oxadiazoles and 1,2,4-oxadiazoles have been prepared and tested for cardiac
myosin ATPase activation in vitro. In all cases, three carbon spacer between the
oxadiazole core and one of the phenyl ring was considered crucial. In case of
1,3,4-oxadiazole, zero to two carbon spacer between oxadiazole core and other
phenyl ring are favorable. Phenyl ring can be replaced by cyclohexyl moiety. In
case of 1,2,4-oxadiazole, zero or one carbon spacer between the oxadiazole and
other phenyl ring are favorable. Introduction of hydrogen bonding donor (NH)
group at the 2nd position of the 1,3,4-oxadiazole enhances the activity.
Substitutions on either of the phenyl rings or change of phenyl ring to other
heterocycle are not tolerated for both the oxadiazoles. The prepared oxadiazoles
showed selective activation for cardiac muscle over smooth and skeleton muscles.
PMID- 29937060
TI - Design and synthesis of bridged piperidine and piperazine isosteres.
AB - We have developed versatile methods toward the synthesis of a variety of
piperidine/piperazine bridged isosteres of pridopidine. The compounds were
assessed against the D2 receptor in agonist and antagonist modes and against the
D4 receptor in agonist mode. hERG Binding and the ADME profiles were studied.
PMID- 29937061
TI - Contact Dermatitis Due to Black Pepper Extract Used to Treat Vitiligo.
PMID- 29937062
TI - Pemphigus Vegetans in the Inguinal Folds.
PMID- 29937063
TI - Clinical, Dermoscopic and Histologic Features of Recurrent Cutaneous Eosinophilic
Vasculitis Cases.
AB - Primary recurrent cutaneous eosinophilic vasculitis is a rare condition
characterized by pruritic, erythematous, purpuric plaques associated to edema. We
compared and analyze the clinical, dermoscopic and histological features of the
disease in 4 patients from our hospital and 13 patients published in the
literature. Seventeen patients were included, with a median age of 56yo, a median
duration of disease of 6 months. Lesions were most frequently generalized (47%)
or localized in lower limbs (41%). The most frequent features were purpuric color
(71%), local edema (65%), necrotizing vasculitis (94%) and eosinophil
infiltration (100%) in histology. Most of the patients (82.4%) were given oral
steroids with a median dose of 30mg. Primary recurrent cutaneous eosinophilic
vasculitis might be an infra-diagnosed condition. The analysis of the patients
allowed us to propose diagnostic criteria for the definition of this disease. We
suggest a therapeutic strategy with high-potency steroids and dapsone, which
might be considered as first-line treatment.
PMID- 29937064
TI - [Penile intra-epithelial neoplasia].
AB - INTRODUCTION: Penile intra-epithelial neoplasia (PIN) are precancerous lesions,
characterized by architectural and cytological abnormalities of the genital
epithelium, from which can arise squamous carcinomas. METHODS: A literature
review was performed on the Medline database, considering the articles listed
between October 2007 and October 2017 dealing with PIN, using the following
keywords "intraepithelial neoplasia" or "Bowen's disease" or "erythroplasia of
Queyrat" or "bowenoid papulosis" and "penis ". Papers were selected according to
their language (English and French) and their relevance. RESULTS: One hundred
seventy four articles related to PIN were listed. Twenty-five of them were
selected for their relevance. The analysis of the references of these articles
identified 6 relevant papers published before October 2007, which were considered
for this review based on a total of thirty-one articles. We describe clinical and
pathological characteristics of PIN, emphasizing treatment modalities.
CONCLUSION: Urologists should distinguish HPV-related and non HPV-related PIN,
both of them sharing clinical presentation, but needing different management.
PMID- 29937065
TI - Surgical Management of Nonallergic Rhinitis.
AB - Nonallergic rhinitis (NAR) describes chronic symptoms of nasal congestion,
obstruction, and rhinorrhea unrelated to a specific allergen based on skin or
serum testing. Vasomotor rhinitis is the most frequent subtype of NAR. Although
medical management is the first-line treatment of NAR, there is a role for
surgical therapy when medications fail to improve symptoms. Surgical options for
NAR include inferior turbinate reduction and botulinum toxin injection as well as
more directed targeting of the autonomic nerve supply to the nasal cavity through
vidian neurectomy, posterior nasal neurectomy, and cryoablation of the posterior
nerve.
PMID- 29937066
TI - Measuring Nasal Obstruction Outcomes.
AB - Methods of measuring nasal obstruction outcomes include both objective anatomic
and physiologic measurements, as well as subjective patient-reported measures.
Anatomic measurements include acoustic rhinometry, imaging studies, and clinician
derived examination findings. Physiologic measures include rhinomanometry, nasal
peak inspiratory flow, and computational fluid dynamics. Patient-reported outcome
measures (PROMs) are self-reported assessments of disease-specific quality-of
life outcomes. Several studies attempted correlation of these outcome measures;
however, few show strong correlation. Expert opinion favors determining
successful surgical outcomes using PROMs. This review provides a summary of
current nasal obstruction outcome measures.
PMID- 29937067
TI - Comparison Between 64Cu-PSMA-617 PET/CT and 18F-Choline PET/CT Imaging in Early
Diagnosis of Prostate Cancer Biochemical Recurrence.
AB - PURPOSE: To evaluate the diagnostic performance of 64Cu-PSMA-617 positron
emission tomography (PET) with computed tomography (CT) for restaging prostate
cancer after biochemical recurrence (BCR) and to compare it with 18F-choline
PET/CT in a per-patient analysis. PATIENTS AND METHODS: An observational study
was performed of 43 patients with BCR after laparoscopic radical prostatectomy
who underwent 64Cu-PSMA-617 PET/CT and subsequently 18F-choline PET/CT for
restaging. The detection rates (DR) of 64Cu-PSMA-617 PET/CT and of 18F-choline
PET/CT were calculated by standardized maximum uptake value (SUVmax) at 4 hours
and SUVmax at 1 hour as reference, respectively. Furthermore, univariate logistic
regression analysis was carried out to identify independent predictive factors of
positivity with 64Cu-PSMA-617 PET/CT. RESULTS: An overall positivity with 64Cu
PSMA-617 PET/CT was found in 32 patients (74.4%) versus 19 (44.2%) with 18F
choline PET/CT. Specifically, after stratifying for prostate-specific antigen
(PSA) values, we found a good performance of 64Cu-PSMA-617 PET/CT at low PSA
levels compared to 18F-choline PET/CT, with a DR of 57.1% versus 14.3% for PSA
0.2-0.5 ng/mL (P = .031), and of 60% versus 30% with PSA 0.5-1 ng/mL. At
univariate binary logistic regression analysis, PSA level was the only
independent predictor of 64Cu-PSMA-617 PET/CT positivity. No significant
difference in terms of DR for both 64Cu-PSMA-617 PET/CT and 18F-choline PET/CT
was found according to different Gleason score subgroups. CONCLUSION: In our
study cohort, a better performance was observed for 64Cu-PSMA-617 PET/CT compared
to 18F-choline PET/CT in restaging after BCR, especially in patients with low PSA
values.
PMID- 29937068
TI - Beyond viral dependence: The pathological consequences of HCV-induced EGF
signaling.
PMID- 29937071
TI - Prospective Evaluation of Predictive Parameters for Urinary Tract Infection in
Patients with Acute Renal Colic.
AB - BACKGROUND: Acute renal colic (ARC) is an emergency that can mostly be treated
conservatively, but can be life threatening in combination with urinary tract
infection (UTI). Assessment for infection includes white blood cell (WBC) count
and C-reactive protein (CRP), but these parameters are often unspecifically
elevated and might lead to antibiotic over-therapy. In times of increasing
antibiotic resistance, however, unnecessary antibiotic therapy should be avoided.
OBJECTIVES: The goal of the study was to investigate the prevalence of UTI proven
by urine culture (UC) in patients with ARC and to identify predictive factors in
the emergency setting. PATIENTS AND METHODS: We prospectively enrolled 200
consecutive patients with ARC and evaluated blood test results, urinalysis, UC,
symptoms suspicious for UTI, and time between symptom onset and admission, as
well as body temperature. Logistic regression analyses were performed to identify
predictive factors. RESULTS: There were 196 patients eligible for statistical
analysis. UTI proven by positive UC was detected in 26 patients (13%). On
multivariate logistic regression analysis, suspicious urinalysis (positive
nitrite or bacteria > 20/high-power field [hpf] or WBC > 20/hpf), patient age >=
54 years and CRP >= 1.5 mg/dL (fivefold increase) were significant predictors for
the presence of UTI. Neither elevated WBC count nor typical UTI symptoms were
associated with UTI. CONCLUSIONS: Based on our results, a routine antibiotic
prophylaxis in patients with ARC does not seem to be appropriate. Patient age and
CRP can help to decide if antibiotic treatment might be indicated, even in case
of a not clearly suspicious urinalysis.
PMID- 29937069
TI - Long-Term Culture of Distal Airway Epithelial Cells Allows Differentiation
Towards Alveolar Epithelial Cells Suited for Influenza Virus Studies.
AB - As the target organ for numerous pathogens, the lung epithelium exerts critical
functions in health and disease. However, research in this area has been hampered
by the quiescence of the alveolar epithelium under standard culture conditions.
Here, we used human distal airway epithelial cells (DAECs) to generate alveolar
epithelial cells. Long-term, robust growth of human DAECs was achieved using co
culture with feeder cells and supplementation with epidermal growth factor (EGF),
Rho-associated protein kinase inhibitor Y27632, and the Notch pathway inhibitor
dibenzazepine (DBZ). Removal of feeders and priming with DBZ and a cocktail of
lung maturation factors prevented the spontaneous differentiation into airway
club cells and instead induced differentiation to alveolar epithelial cells. We
successfully transferred this approach to chicken distal airway cells, thus
generating a zoonotic infection model that enables studies on influenza A virus
replication. These cells are also amenable for gene knockdown using RNAi
technology, indicating the suitability of the model for mechanistic studies into
lung function and disease.
PMID- 29937070
TI - Base Excision Repair Gene Polymorphisms and Wilms Tumor Susceptibility.
AB - Base excision repair (BER) is the main mechanism to repair endogenous DNA lesions
caused by reactive oxygen species. BER deficiency is linked with cancer
susceptibility and premature aging. Single nucleotide polymorphisms (SNPs) within
BER genes have been implicated in various human malignancies. Nevertheless, a
comprehensive investigation of their association with Wilms tumor susceptibility
is lacking. In this study, 145 cases and 531 sex and age-matched healthy controls
were recruited. We systematically genotyped 18 potentially functional SNPs in six
core BER pathway genes, using a candidate SNP approach. Logistic regression was
employed to evaluate odds ratio (OR) and 95% confidence interval (CI) adjusted
for age and gender. Several SNPs showed protective effects against Wilms tumor.
Significant associations with Wilms tumor susceptibility were shown for hOGG1
rs1052133 (dominant: adjusted OR = 0.66, 95% CI = 0.45-0.96, P = .030), FEN1
rs174538 (dominant: adjusted OR = 0.66, 95% CI = 0.45-0.95, P = .027; recessive:
adjusted OR = 0.54, 95% CI = 0.32-0.93 P = .027), and FEN1 rs4246215 (dominant:
adjusted OR = 0.55, 95% CI = 0.38-0.80, P = .002) polymorphisms. Stratified
analysis was performed by age, gender, and clinical stage. Moreover, there was
evidence of functional implication of these significant SNPs suggested by online
expression quantitative trait locus (eQTL) analysis. Our findings indicate that
common SNPs in BER genes modify susceptibility to Wilms tumor.
PMID- 29937072
TI - Regarding the Joint Statement From the American College of Surgeons Committee on
Trauma and the American College of Emergency Physicians Regarding the Clinical
Use of Resuscitative Endovascular Balloon Occlusion of the Aorta.
PMID- 29937073
TI - The gastro-renal effects of intra-abdominal hypertension: Implications for
critical care nurses.
AB - Intra-abdominal hypertension is classified as either primary or secondary -
primary occurs due to intra-abdominal or retro-peritoneal pathophysiology,
whereas secondary results in alterations in capillary fluid dynamics due to
factors, such as massive fluid resuscitation and generalised inflammation. The
renal and gastro-intestinal effects occur early in the progression of intra
abdominal hypertension, and may lead to poor patient outcomes if not identified.
As a direct response to intra-abdominal hypertension, renal function is reduced
with remarkable impairment from pressures of around 10 mmHg, oliguria developing
at 15 mmHg and anuria developing at 30 mmHg. Intestinal micro-circulation is
significantly reduced by up to 50% with intra-abdominal pressures as low as 15
mmHg. Mucosal and submucosal tissue hypo-perfusion causes considerable damage to
the intestinal cells, potentially resulting in bacterial translocation, endotoxin
release, sepsis and multiple organ failure. The critical care nurse plays an
important role in the early identification of intra-abdominal hypertension
however, without this essential knowledge base and comprehension of intra
abdominal hypertension, clinical signs and symptoms may go unnoticed or be
misinterpreted as signs of other critical illnesses.
PMID- 29937074
TI - Experiences of family caregivers the first six months after patient diagnosis of
necrotising soft tissue infection: A thematic analysis.
AB - BACKGROUND: Necrotising soft tissue infection, or necrotising fasciitis, is a
rapidly progressing disease requiring immediate diagnosis and treatment
consisting of antimicrobial therapy, hyperbaric oxygen, debridement surgery and
treatment in the intensive care unit. The harrowing illness trajectory affects
the family caregivers potentially producing long-term psychological issues.
OBJECTIVES: We aimed to explore the experiences and coping strategies of family
caregivers during the first six months after patient diagnosis of necrotising
soft tissue infection. METHODS: Our study had a prospective, explorative,
qualitative design using semi-structured interviews and thematic analysis to
understand necrotising soft tissue infection as an intrinsic and instrumental
case. Family caregivers (n = 25) were recruited at three university hospitals in
Denmark and Sweden. FINDINGS: We identified three chronological themes describing
issues of importance to the family caregivers. In the intensive care unit: Coping
with illness and intensive care; In the ward: Coping with injury and post
intensive care and At home: Coping with recovery and new home life. CONCLUSION:
Challenges facing family caregivers of necrotising soft tissue infections
survivors are still under-recognised. Healthcare professionals need to ensure
that families and stakeholders throughout the patient trajectory have access to
and co-create timely information and care plans to bridge the knowledge gap
across care environments and to relieve family responsibility.
PMID- 29937075
TI - Post-traumatic stress symptoms in family caregivers of intensive care unit
patients: A longitudinal study.
AB - OBJECTIVES: To describe the prevalence and trajectory of family caregivers' post
traumatic stress symptoms during the first year after a patient's admission to
the intensive care unit and identify associations between family caregivers'
background characteristics, hope and post-traumatic stress symptoms. RESEARCH
METHODOLOGY/DESIGNS: Family caregivers of intensive care unit patients (n = 211)
completed questionnaires at patient admission to the intensive care unit and
thereafter at 1, 3, 6, and 12 months. Mixed-model analyses were performed.
SETTING: Four intensive care units in a university hospital in Norway. MAIN
OUTCOME MEASURES: Impact of Event Scale-Revised and Herth Hope Index. RESULTS: On
admission, 54% of family caregivers reported high post-traumatic stress symptom
levels, which decreased during the first six months after patient discharge.
Lower levels of hope, being younger, having more comorbidities and being on sick
leave were associated with higher post-traumatic stress symptom levels. Being the
parent of the patient was associated with decreased post-traumatic stress symptom
levels. CONCLUSIONS: Family caregivers of intensive care unit patients report
high levels of post-traumatic stress symptoms. Higher levels of hope were
associated with fewer post-traumatic stress symptoms.
PMID- 29937076
TI - Stress, stress-related symptoms and social support among Taiwanese primary family
caregivers in intensive care units.
AB - OBJECTIVES: To explore the associations between stress, sleep disturbances,
fatigue severity and social support among primary family caregivers in intensive
care units during the early period of ICU hospitalisation. DESIGN: Cross
sectional, descriptive correlational study. SETTING: Intensive Care Units in a
teaching hospital in Taiwan. MAIN OUTCOME MEASURES: Perceived stress (Impact of
Events Scale-Revised), sleep disturbances (General Sleep Disturbance Scale),
fatigue severity (Lee's Fatigue Scale), social support (Norbeck Social Support
Questionnaire) and one open-ended question. RESULTS: The primary family
caregivers (N = 87) were distressed and experienced poor sleep quality and
fatigue during the early period of ICU hospitalisation. Primary family caregivers
have various social support needs but being updated on the patients' prognosis
was at the top of the list. Perceived ICU hospitalisation stress was the only
significant predictor for fatigue while age along with perceived event stress
were the significant predictors for sleep disturbances. CONCLUSION: Stress-coping
interventions are needed to reduce stress-related symptoms for the primary family
caregivers. Social supports did not buffer stress in this study, which calls for
further research to explore the culture variance and quality of social support.
PMID- 29937077
TI - Developing family-centred care in a neonatal intensive care unit: An action
research study.
AB - AIM: To develop, implement and evaluate family-centred interventions to promote
parental involvement in caregiving in a Neonatal Intensive Care Unit.
METHODOLOGY: A participatory action research approach was used to implement two
changes in practice a) improved skin-to-skin contact b) unlimited parental
presence at the cot-side. The changes were underpinned by a family-centred
philosophy of care and education. Data were collected from staff using a
questionnaire, focus groups and interviews, and from parents using focus groups
and interviews. Qualitative data were analysed using Framework and quantitative
data analysed using descriptive and t-test statistics. SETTING: A Neonatal
Intensive Care Unit in England. FINDINGS: Changes in practice were successfully
implemented. Nurses reported positively on improvements in Family Centred Care;
most notably information-sharing with parents, providing family support, enabling
parental participation in care and improved competence supporting parents in care
giving. These changes were reflected in parental feedback. CONCLUSION:
Understanding the context of the neonatal unit can support cultural change when
change is actively facilitated and owned by the staff concerned. Acknowledging
parents as the main caregiver can be challenging for nurses and they require
support and education to enable them to manage the changes necessary to provide
Family-Centred Care.
PMID- 29937078
TI - Acceptability and feasibility of an interprofessional end-of-life/palliative care
educational intervention in the intensive care unit: A mixed-methods study.
AB - OBJECTIVES: This study aimed to describe a seven hour End-of-Life/Palliative Care
educational intervention including online content related to symptom management,
communication and decision-making capacity and an in-person group integration
activity, from the perspective of the interprofessional team in terms of its
acceptability and feasibility. RESEARCH DESIGN: A mixed-methods study design was
used. SETTING AND SAMPLE: The study was conducted in a medical-surgical Intensive
Care Unit in Montreal, Canada. The sample consisted of 27 clinicians of the
Intensive Care Unit interprofessional team who completed the End-of
Life/Palliative Care educational intervention, and participated in focus groups
and completed a self-administered questionnaire. MAIN OUTCOME MEASURES: The main
outcomes were the acceptability and feasibility of the educational intervention.
FINDINGS: The intervention was perceived to be appropriate and suitable in
providing clinicians with knowledge and skills in symptom management and
communication through self-reflection and self-evaluation, provision of
assessment tools and promotion of interprofessional teamwork. The online format
was more feasible, but the in-person group activity was key for the integration
of knowledge and the promotion of interprofessional discussions. CONCLUSION:
Findings suggest that an interprofessional educational intervention integrating
on-line content with in-person training has the potential to support clinicians
in providing quality End-of-Life/Palliative Care in the Intensive Care Unit.
PMID- 29937080
TI - [Management of medication errors in general medical practice: Study in a
pluriprofessionnal health care center].
AB - BACKGROUND: Medication errors are the most frequent medical care adverse events
in France. Their management process used in hospital remains poorly applied in
primary ambulatory care. OBJECTIVES: The main objective of our study was to
assess medication error management in general ambulatory practice. The secondary
objectives were the characterization of the errors and the analysis of their root
causes in order to implement corrective measures. METHODS: The study was
performed in a pluriprofessionnal health care house, applying the stages and
tools validated by the French high health authority, that we previously adapted
to ambulatory medical cares. RESULTS: During the 3 months study 4712 medical
consultations were performed and we collected 64 medication errors. Most of
affected patients were at the extreme ages of life (9,4 % before 9 years and 64 %
after 70 years). Medication errors occurred at home in 39,1 % of cases, at
pluriprofessionnal health care house (25,0 %) or at drugstore (17,2 %). They led
to serious clinical consequences (classified as major, critical or catastrophic)
in 17,2 % of cases. Drug induced adverse effects occurred in 5 patients, 3 of
them needing hospitalization (1 patient recovered, 1 displayed sequelae and 1
died). In more than half of cases, the errors occurred at prescribing stage. The
most frequent type of errors was the use of a wrong drug, different from that
indicated for the patient (37,5 %) and poor treatment adherence (18,75 %). The
systemic reported causes were a care process dysfunction (in coordination or
procedure), the health care action context (patient home, not planned act,
professional overwork), human factors such as patient and professional condition.
The professional team adherence to the study was excellent. CONCLUSION: Our study
demonstrates, for the first time in France, that medication errors management in
ambulatory general medical care can be implemented in a pluriprofessionnal health
care house with two conditions: the presence of a trained team coordinator, and
the use of validated adapted and simple processes and tools. This study also
shows that medications errors in general practice are specific of the care
process organization. We identified vulnerable points, as transferring and
communication between home and care facilities or conversely, medical
coordination and involvement of the patient himself in his care.
PMID- 29937081
TI - Trajectories of Body Mass Index from Childhood to Young Adulthood among Patients
with Type 1 Diabetes-A Longitudinal Group-Based Modeling Approach Based on the
DPV Registry.
AB - OBJECTIVE: To identify distinct longitudinal patterns of body mass index (BMI) z
score in type 1 diabetes from childhood to young adulthood and secondly to
determine sex differences as well as associated clinical covariates. STUDY
DESIGN: A total of 5665 patients with type 1 diabetes (51% male) with follow-up
from 8 to 20 years of age from the multicenter diabetes prospective registry DPV
were studied (baseline diabetes duration >=1 years, BMI z score aggregated per
year of life). Latent class growth modeling (SAS: PROC TRAJ) was applied to
analyze BMI z score over time. RESULTS: Six distinct BMI z score trajectories
were identified (group 1: 7% of patients, group 2: 22%, group 3: 20%, group 4:
16%, group 5: 25%, and group 6: 10%). Group 1, 2, 5, and 6 had an almost stable
BMI z score, either in the low, near-normal, high stable, or chronic overweight
range. Group 3 (60% girls) increased their BMI during puberty, whereas group 4
(65% boys) had a BMI decrease. Similar patterns were observed for girls only,
whereas boys followed nearly stable trajectories without fluctuation over time.
Between the near-normal and the other groups, significant differences (P < .05)
in sex ratio, migration background, mental health, height z score, glycated
hemoglobin A1c, diabetes treatment, dyslipidemia, hypertension, and smoking were
observed. CONCLUSIONS: In youth with type 1 diabetes, a great heterogeneity of
BMI z score trajectories exists that highlight the importance of personalized sex
specific intervention programs for subjects at risk for unfavorable BMI
development.
PMID- 29937082
TI - Guardians at the Gate: Pediatricians, Colic and Clinical Research.
PMID- 29937083
TI - Multiple Bullae Associated with Human Parvovirus B19.
PMID- 29937084
TI - Hospital Anxiety and Depression Scale (HADS): Validation in Mexican Patients with
Inflammatory Bowel Disease.
AB - INTRODUCTION: The Hospital Anxiety and Depression Scale (HADS) is a self
administered instrument for outpatients, but its behaviour differs according to
the clinical population to which it is applied. In Mexico it is not validated in
patients with Inflammatory Bowel Disease (IBD). OBJECTIVES: To validate the HADS
scale in the Mexican population with IBD. METHODS: 112 patients with IBD from the
"Salvador Zubiran" National Institute of Medical Sciences and Nutrition were
included, to whom the HADS was applied and some demographic and clinical
characteristics of the disease were evaluated. An exploratory factor analysis was
performed and factorial congruence was calculated to determine the construct
validity of the HADS, while reliability was evaluated using Cronbach's alpha.
RESULTS: The result of the varimax rotation of the 14 items of the HADS explained
50.1% of the variance, having two main factors. Ten items showed high factor
loading for the dimensions originally proposed. The internal consistency of the
HADS was high (alpha=0.88) with high values for the congruence coefficients.
CONCLUSIONS: The HADS scale is a valid instrument to detect possible cases of
Anxiety and Depression in Mexican patients with IBD. The validation of this
instrument allows its routine use for the integral evaluation of the patient and
their timely referral to mental health.
PMID- 29937085
TI - Care Should Be Exercised When Titling Articles So as to Not Mislead Readers.
PMID- 29937086
TI - Interpreting the Results in Terms of Clinical Significance: Comment on "Shoe
Orthotics for the Treatment of Chronic Low Back Pain: A Randomized Controlled
Trial".
PMID- 29937087
TI - Response From the Editors.
PMID- 29937088
TI - Complementary Medicine in Parkinson Disease: Once Again, Surprisingly Effective.
PMID- 29937089
TI - Reply to the letter regarding "Population-based survey of inpatient pediatric
tonsillectomy and postoperative hemorrhage in Taiwan, 1997-2012."
PMID- 29937090
TI - Active disturbance rejection boundary control of Timoshenko beam with tip mass.
AB - In this paper, the active disturbance rejection control (ADRC) is utilized to
stabilize the vibration of perturbed Timoshenko beam model with tip mass. The
boundary control design is based on a hybrid PDE-ODE model, and is accompanied
with designing a high-gain extended state observer (ESO) that is used to estimate
the boundary disturbances. By transforming the model into the appropriate state
space, the semigroup theory is employed to prove the well-posedness of the closed
loop system. To this end, it is proved by a frequency domain method that the
semigroup generated by the system operator is exponentially stable, which allows
to conclude the boundedness of perturbed closed-loop system response. The
stability of the closed-loop system is further analyzed using the Lyapunov
approach. Simulation results are presented to illustrate the efficacy of the
suggested method.
PMID- 29937091
TI - Fault tolerant system based on non-integers order observers: Application in a
heat exchanger.
AB - This work presents a fault-tolerant (FT) scheme based on the application of non
integer order observers also called fractional observers, the case of study is a
double pipe countercurrent heat exchanger (HE). The aim of the FT is to detect
sensors faults as soon as possible, and to provide a healthy signal in order to
replace the faulty sensor signal by the fractional observer estimation. To
develop the FT scheme a bank of high gain fractional order observers (HGFOO) is
proposed. The Riemann-Liouville (RL) fractional derivative definition is used to
solve each fractional observer. Experimental measures from a HE were used to test
the performance of the fractional observers and the control scheme. The results
show the robustness of the proposed observers.
PMID- 29937092
TI - Natural Selection Has Differentiated the Progesterone Receptor among Human
Populations.
AB - The progesterone receptor (PGR) plays a central role in maintaining pregnancy and
is significantly associated with medical conditions such as preterm birth that
affects 12.6% of all the births in U.S. PGR has been evolving rapidly since the
common ancestor of human and chimpanzee, and we herein investigated evolutionary
dynamics of PGR during recent human migration and population differentiation. Our
study revealed substantial population differentiation at the PGR locus driven by
natural selection, where very recent positive selection in East Asians has
substantially decreased its genetic diversity by nearly fixing evolutionarily
novel alleles. On the contrary, in European populations, the PGR locus has been
promoted to a highly polymorphic state likely due to balancing selection.
Integrating transcriptome data across multiple tissue types together with large
scale genome-wide association data for preterm birth, our study demonstrated the
consequence of the selection event in East Asians on remodeling PGR expression
specifically in the ovary and determined a significant association of early
spontaneous preterm birth with the evolutionarily selected variants. To
reconstruct its evolutionary trajectory on the human lineage, we observed
substantial differentiation between modern and archaic humans at the PGR locus,
including fixation of a deleterious missense allele in the Neanderthal genome
that was later introgressed in modern human populations. Taken together, our
study revealed substantial evolutionary innovation in PGR even during very recent
human evolution, and its different forms among human populations likely result in
differential susceptibility to progesterone-associated disease conditions
including preterm birth.
PMID- 29937094
TI - WASP (Write a Scientific Paper): Preparing a poster.
AB - A poster is a visual communication tool, but crucially, it is absolutely not a
research paper directly transposed onto a board. It shows the results of research
but it does not explain in detail in the way that a conventional paper does. This
paper will explain how poster creation accedes to newspaper article writing
theory, while adhering to the IMRAD (Introduction, Methods, Results, and
Discussion) format.
PMID- 29937093
TI - Inferring Identical-by-Descent Sharing of Sample Ancestors Promotes High
Resolution Relative Detection.
AB - As genetic datasets increase in size, the fraction of samples with one or more
close relatives grows rapidly, resulting in sets of mutually related individuals.
We present DRUID-deep relatedness utilizing identity by descent-a method that
works by inferring the identical-by-descent (IBD) sharing profile of an
ungenotyped ancestor of a set of close relatives. Using this IBD profile, DRUID
infers relatedness between unobserved ancestors and more distant relatives,
thereby combining information from multiple samples to remove one or more
generations between the deep relationships to be identified. DRUID constructs
sets of close relatives by detecting full siblings and also uses an approach to
identify the aunts/uncles of two or more siblings, recovering 92.2% of real
aunts/uncles with zero false positives. In real and simulated data, DRUID
correctly infers up to 10.5% more relatives than PADRE when using data from two
sets of distantly related siblings, and 10.7%-31.3% more relatives given two sets
of siblings and their aunts/uncles. DRUID frequently infers relationships either
correctly or within one degree of the truth, with PADRE classifying 43.3%-58.3%
of tenth degree relatives in this way compared to 79.6%-96.7% using DRUID.
PMID- 29937095
TI - WASP (Write a Scientific Paper): Presenting scientific work.
AB - The presentation of scientific work resembles popular media narratives far more
than it does the traditional paper writing that scientists are trained in. In the
former, a good 'hook' is essential so as to hang a paper that is presented as a
slide show, an abstract, a poster or text directly addressed to the media, and
this hook must be obvious and apparent up front. A slight element of truthful
sensationalism is therefore often helpful. This set of Best Practice Guidelines
will offer factual and practical guidelines with regard to preparing research in
these formats since self-presentation is essential for career progression. It is
not only what we do but how we are seen to be doing it, acceding to Batman's
aphorism: "it's not who I am underneath but what I do that defines me". Research
preparation and presentation and skills of all sorts are thus increasingly
critical in the increasingly competitive world of academia.
PMID- 29937096
TI - Comparative physiology of the ductus arteriosus among vertebrates.
AB - The ductus arteriosus is typically viewed as a mammalian fetal blood vessel
providing a right-to-left shunt of right ventricular outflow away from the lungs
and to the systemic circuit, that must close at birth. This review provides a
wider comparative examination of the ductus arteriosus in lungfish, reptiles,
birds, and mammals. The ductus arteriosus evolved with the lung in the ancestors
of the lungfish as a connection between the pulmonary arteries and dorsal aorta.
During embryonic development, reptiles, birds, and mammals all possess either one
or two paired ductus arteriosi that provide a fetal shunt of blood away from the
lungs. Differences in the fetal circulatory arrangement are seen between these
groups and this influences the importance of the ductus arteriosus as an
embryonic shunt. The ductus arteriosus from lungfish and tetrapod vertebrates is
an oxygen sensitive blood vessel, with shared conserved pathways involved in
oxygen sensing. By expanding studies into more comparative models such as
lungfish or developing birds a better understanding of the physiology of the
ductus arteriosus can be developed.
PMID- 29937097
TI - Serum neurofilament light chain in progressive supranuclear palsy.
AB - INTRODUCTION: Neurofilament light chain (NfL) is a promising biomarker in
neurodegenerative diseases. Elevated NfL levels in CSF and blood have been
observed in a growing number of neurodegenerative disorders, including
frontotemporal dementia and Alzheimer's disease. We studied serum NfL levels in
patients with progressive supranuclear palsy (PSP) in relation to disease
severity and survival. METHODS: Serum NfL levels were determined cross
sectionally in a retrospective cohort of 131 patients with PSP and 95 healthy
controls. Detailed clinical examination was performed and disease severity was
assessed by several rating scales. RESULTS: We found that serum NfL levels in PSP
were twice as high as those in controls, and that NfL levels correlated with
worse functional, motor and cognitive functioning. During follow-up, 119 PSP
patients had died, and higher NfL levels were associated with a shorter survival.
CONCLUSION: This study provides evidence that serum NfL is a relevant and
promising biomarker in PSP for disease severity, and may be used as a prognostic
tool to predict survival in clinical practice.
PMID- 29937098
TI - Essential tremor: "Plus" or "Minus". Perhaps now is the time to adopt the term
"the essential tremors".
PMID- 29937100
TI - Regulating landfills using measured methane emissions: An English perspective.
AB - Methane emissions from landfills are an important source of greenhouse gases in
the UK and worldwide. This paper considers how measurements of methane emissions
could be used to regulate landfills in England in order to reduce the
contribution of landfilling to climate change. The paper presents the results of
a number of UK studies undertaken to quantify methane emissions from landfills.
The methods used have included the DIAL (Differential Absorption Lidar) technique
and a tracer gas dispersion method. A method based on aerial measurements has
been developed. Methane emission rates were measured at 15 biodegradable waste
landfills. All of the landfills where measurements took place had an active
landfill gas extraction system. A methane collection index (MCI) is calculated
for each landfill using the ratio of the methane collection rate to the sum of
the collection and emission rates. The values of the index in the campaigns
reported here ranged from 0.28 to 0.90. The modern operational landfills surveyed
achieved MCI values with a much narrower range of between 0.64 and 0.90 with an
average of 0.76. This has demonstrated that it is possible for these landfills to
collect a high proportion of the landfill gas. A proposed approach is presented
for regulating landfills using the measured MCI. This would involve an annual
measurement campaign to quantify the methane emissions and the use of the data
provided by these surveys to develop an achievable but challenging MCI limit. A
limit value of 0.75 for the MCI is used to illustrate the approach. An MCI that
falls below the limit would trigger actions to reduce the methane emissions from
the landfill.
PMID- 29937101
TI - Camptocormia: a consensus for grading on a curve.
PMID- 29937099
TI - Retinal changes in Parkinson's disease and glaucoma.
AB - BACKGROUND: The topic of retinal neurodegeneration in PD is controversial,
therefore the objective was to compare macular ganglion cell complex (mGCC) and
peripapillary retinal nerve fiber layer (pRNFL) thickness in PD using 2 Spectral
Domain (SD) Optical Coherence Tomography (OCT) devices. METHODS: In total, 146
eyes of 130 age-similar patients were included, of these 46 eyes of 30 PD
patients, 60 eyes of 60 glaucoma patients and 40 eyes of 40 healthy controls.
Peripapillary RNFL and mGCC were measured. Correlation analyses were performed
for evaluation of association between pRNFL or mGCC and PD severity using the
Movement Disorder Society (MDS)-Unified Parkinson Disease Rating Scale (UPDRS).
Scatterplots were used to evaluate relationships between disease duration,
dopamine dose, olfactory assessment and retinal thickness. RESULTS: No
significant difference was found for both eyes of PD patients compared to healthy
subjects neither for overall mGCC nor each sector. However, the ipsilateral eye
to the most-affected body side with bradykinesia in PD patients had a
statistically significant thinner superior pRNFL compared to healthy controls (P
= 0.03). There was no significant correlation between pRNFL or mGCC and disease
severity; also, the scatterplots did not indicate a correlation between disease
duration, dopamine dose, olfactory testing and OCT results. CONCLUSIONS: Imaging
of the retina revealed thinning of some retinal layers of the ipsilateral eye to
the most-affected body side in PD patients compared to healthy controls.
Peripapillary RNFL and mGCC did not correlate to disease severity; however, this
was a fairly small and heterogeneous group of PD patients.
PMID- 29937102
TI - Developing a Guideline for Endotracheal Suctioning of Adults With Artificial
Airways in the Perianesthesia Setting in China.
AB - PURPOSE: This study aimed to adapt a guideline for endotracheal suctioning of
adults with artificial airways in the perianesthesia setting in China. DESIGN:
This study was guided by the ADAPTE framework. METHODS: The development process
consisted of setup, adaptation, and finalization phases. A heterogeneous
consultant panel that included a patient representative was established to
contribute guidance and suggestions regarding guideline development. Relevant
evidence documents were searched, critically appraised, selected, and synthesized
to develop the draft guideline. After revisions, the adapted guideline was
evaluated by 20 external reviewers. FINDINGS: A 155-page adapted guideline was
developed with 26 key recommendations (including 3 procedure phases and 17 points
of care). CONCLUSIONS: The adapted guideline provided the best evidence for
endotracheal suctioning of adults with artificial airways and supported
practitioner decisions about appropriate endotracheal suctioning practices for
this population. The study also lays the groundwork for future projects on
quality improvement and knowledge translation.
PMID- 29937103
TI - The impact of nasal airflow on sinus mucosa: A radiographic review.
AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a disease of widespread prevalence
and high morbidity. Many suggest that the introduction of toxins and allergens
via nasal airflow plays a significant role in the development of CRS. In patients
who have undergone total laryngectomy, nasal airflow is disrupted, providing an
opportunity to examine the role of nasal airflow in sinonasal pathology. METHODS:
All patients who received a total laryngectomy between 2002 and 2012 with
preoperative and postoperative computed tomography (CT) scans were
retrospectively reviewed. The Lund-Mackay (LM) score for each sinus was recorded
for both scans. The assessment of differences in pre-operative and post-operative
LM scores was analyzed utilizing paired t-tests. RESULTS: 56 patients underwent
total laryngectomy and had both preoperative and postoperative CT scans. There
were no significant differences in the LM scores between pre-operative and post
operative scans within each sinus (frontal sinus, p = 1.0; anterior ethmoid
sinus, p = 0.77; posterior ethmoid sinus, p = 0.45; maxillary sinus, p = 0.90;
sphenoid sinus, p = 0.63; ostiomeatal complex, p = 0.78) or in the total LM
scores (p = 0.97). Furthermore, patients with pre-operative sinonasal mucosal
thickening (total LM score > 0) showed no significant change in their total LM
score post-operatively (p = 0.13). CONCLUSION: In total laryngectomy patients,
studies demonstrate that a disruption in nasal airflow is correlated to altered
sinonasal physiology and decreased subjective symptoms. However, our study shows
that the disruption of nasal airflow results in no significant change in
radiographic evidence of sinonasal mucosal thickening.
PMID- 29937104
TI - Preoperative radiation and complication rates after double free flap
reconstruction of head and neck cancer.
AB - INTRODUCTION: In this study, we explore whether preoperative external beam
radiation affects complication rates in patients that have undergone double
simultaneous free tissue transfer for head and neck defects. STUDY DESIGN,
SETTING, SUBJECTS AND METHODS: Approval was obtained from the JPS Institutional
Review Board. We performed a retrospective analysis of patients who underwent
double free flap reconstruction of head and neck defects between August 1997 and
April 2017. Minimum follow up was 6 months. Patients were grouped according to
preoperative radiation status (XRT vs non-XRT). The chi-squared test was used for
all comparisons. P-values and 95% confidence intervals (CI) were reported as (P,
95% CI). RESULTS: 90 flaps were performed on 45 patients. The most common flap
combination utilized was fibula plus radial forearm free flap (RFF) in 17 out of
45 patients. There were no statistically significant differences in frequency of
flap failure (0.35, -15.9-20.1), wound infection (0.75, -22.1-19.3), hematoma
(0.16, -5.3-36.7), or fistula formation (0.69, -22.5-24.6). There were also no
statistically significant differences in cardiac complications (0.57, -10.3-28.2)
and DVT (0.22, -12.4-25.3). CONCLUSION: Our findings suggest that double free
flap patients who had preoperative radiation are not more likely to have
complications compared to non- radiated patients. Simultaneous double free flaps
should be reserved for the most complex cases. Extensive discussion should be had
with the patient about possible morbidity and mortality.
PMID- 29937105
TI - Embracing early recovery after surgery (ERAS) protocols: Is it time for
otolaryngology to join the parade?
PMID- 29937106
TI - The usefulness of low radiation dose subtraction coronary computed tomography
angiography for patients with calcification using 320-row area detector CT.
AB - BACKGROUND: Although subtraction coronary computed tomography angiography (S
CCTA) has recently been developed to improve the diagnostic ability in patients
with severe calcification, increase in radiation exposure remains a concern. The
usefulness of S-CCTA using a low-radiation dose protocol was investigated.
METHODS: S-CCTA in 320-row area detector CT was performed on 84 consecutive
patients with suspected obstructive coronary artery disease with Agatston score
>=100. Reconstruction and radiation dose were changed according to the slow
filling time (SF) (137.5ms=275ms: full reconstruction with 70% reduction) at a tube voltage
of 100kV. The percentage of patients with non-diagnostic stenosis of calcified
coronary artery lesions was calculated in conventional (C-) CCTA, and S-CCTA was
calculated based on 84 patients (446 segments) bases. In 27 patients (137
segments) examined by invasive coronary angiography (ICA), the diagnostic ability
was investigated regarding the ICA findings as reference standard. RESULTS: The
percentage of non-diagnostic patients and segments on C-CCTA vs. S-CCTA was 40.5%
vs. 9.5% and 16.4% vs. 2.9%, respectively. The Agatston score was 589.3+/-655.3,
and the total effective radiation dose (non-contrast scan and C-CCTA) was 2.7+/
1.1mSv. In the 27 patients, 137 segments area under the curve of S-CCTA (0.939,
95% CI: 0.895-0.983) for the ICA findings as reference standard was significantly
higher than that of C-CCTA (0.785, 95% CI: 0.713-0.858) (p<0.0001). CONCLUSION:
The diagnostic ability of S-CCTA performed following the low-radiation dose
protocol for patients with calcification was superior to that of C-CCTA alone.
PMID- 29937107
TI - Prevalence and outcomes for assisted home feeding in medically complex neonates.
AB - OBJECTIVE: To describe the prevalence and outcome of assisted home feeding (AHF)
in medically complex neonatal intensive care unit (NICU) patients, and to
identify variables associated with AHF in this population. STUDY DESIGN: 1223
infants who survived to discharge from 2013 to 2015 were identified in our single
center, retrospective cohort study at a large tertiary referral NICU. Demographic
and selected disease-specific variables were compared between infants discharged
on full oral feeding (PO) versus AHF. RESULT: 404 (33%) infants were discharged
on AHF (NG = 201, GT = 186, NJ = 17). AHF neonates were born at an earlier
gestational age, lower birth weight, had longer hospital admission, greater post
menstrual age at discharge, and had more associated co-morbidities compared to
the PO group. CONCLUSION: AHF was a frequently used and safe intervention in our
large cohort of infants. LEVEL OF EVIDENCE: Treatment Study Level III.
PMID- 29937108
TI - [The Rouen Expert center in the diagnosis and multidisciplinary management of
endometriosis: A French pilot experiment].
AB - OBJECTIVES: To retrospectively describe the activity of the Diagnosis and
Multidisciplinary Management of Endometriosis Expert Center of Rouen-Normandy,
before and after official identification by French Health Authorities. METHODS:
Retrospective study of the main activities of an Expert Center, from January 2013
to March 2018. RESULTS: The Endometriosis Expert Center of Rouen-Normandy is a
regional network, organised as a pyramid with a Referral Center at the top (the
Rouen University Hospital) leading a network of public and private Expertise
Centers below in Normandy. Ten to 11 Multidisciplinary Team meetings per year
were organised, allowing the study of 15 to 20 cases by physicians coming from up
to 17different places (hospital, clinic or private practice). 2066patients
diagnosed with endometriosis were hospitalised in the Referral Center, among them
615were operated for colorectal endometriosis, among which 607by laparoscopy
(97%). The surgical team was multidisciplinary in 444surgeries (72.2%). 50cycles
of fertility preservation (oocyte freezing) were led. Research activity allowed
the publication of 76scientific articles, among which 41 (53.9 %) in a journal of
rank SIGAPS A or B. Medical training was organised for active health
professionals as well as students, including school nurses. CONCLUSION: The
Endometriosis Expert Center of Rouen-Normandy pilot project has helped improving
the diagnosis and better management of the disease in Normandy. This experiment
could be exported to all the other regions of France, in order to unit health
professionals with the aim of a national fight program against endometriosis.
PMID- 29937109
TI - [Sport: A key element for myometrial contractility and regulation of adipokines
in obese pregnant women?]
AB - Obesity is a major public health problem. Pregnant women are also affected by
this epidemic. In pregnant women, obesity increases obstetric and neonatal
complications, and is associated with alterations in the quality of labor that
could be explained by reduced myometrial contractility. This leads to an increase
in the rate of caesarean sections and postpartum haemorrhages in this population
at risk. Adipokines, hormones secreted by adipose tissue, may have a role in
altering the myometrial contractility. Weight loss in these patients is based on
dietary management and on physical activity, which could be a way to improve
adipokines action and uterine contractility. The objective of this literature
review was to review current knowledge about the role of adipokines on uterine
contractility in obese pregnant women and to assess the interest of sport in
improving contractility and in reducing obstetric complications in these women.
PMID- 29937110
TI - The TEACH trial: Tailored education to assist label comprehension and health
literacy.
AB - BACKGROUND: Prior work demonstrated significantly improved prescription label
comprehension and functional health literacy (FHL) using an educational
intervention and redesigned prescription label. OBJECTIVE: The objective of this
study was to assess the effectiveness of the educational intervention to improve
prescription label understanding using three factors: (1) redesigned prescription
label, (2) previously validated MLT and (3) pillbox fill test. METHODS: English
speaking patrons >=55 years old taking >=2 prescription medications were
recruited in this prospective, multisite, randomized, controlled, pre-post study,
in California, Illinois, and Ohio. Participants completed the MLT (25 points) as
a test of label comprehension and filled a 7 * 4 pillbox (Pillbox test, 35
points) at baseline and 1-month follow-up. The intervention group received
tailored education by a student or pharmacist on how to read the label based on
their response to the MLT and Pillbox Test. RESULTS: Combined data analysis was
conducted of the 92 (63.4%) completed follow-ups from all sites. Baseline
characteristics were comparable between control and intervention groups. Overall,
mean MLT increased in both control and intervention groups (DeltaPre-Post: +0.7
point vs. +0.8 point, p < 0.05). Although not statistically significant, pillbox
test scores increased by 2.0 points in the intervention group compared to a
slight decrease in the control group (-0.8 point, p > 0.05). Significant
correlation between MLT and Pillbox scores was observed (r = 0.63, p < 0.05).
Subgroup analysis between sites revealed that the CA-site had lower educational
background and English proficiency; lower mean MLT and Pillbox Fill pre-scores
compared to the IL- and OH-sites, with a statistically significant effect of
intervention on MLT and Pillbox post-scores. CONCLUSIONS: This study extended
earlier findings that focused education using redesigned Rx labels helped improve
Rx label comprehension and observed action. Larger studies are needed to
determine the impact on patient outcomes. Patients with lower education, English
proficiency, and/or FHL may benefit from education that could translate into
improved medication use behavior.
PMID- 29937111
TI - Improving informed consent in cardiac surgery by enhancing preoperative
education.
AB - OBJECTIVE: To investigate the effect of enhancing preoperative education in
improving recall and understanding of a surgical procedure and its application to
the informed consent process in cardiac surgery. METHODS: Four electronic
database searches were performed from January 2000 to August 2017. A total of 282
articles were identified from which 22 prospective studies assessing an
intervention were selected according to predefined selection criteria. RESULTS:
Most articles that used additional written information and all that used
multimedia presentations to enhance informed consent showed that their
intervention improved risk recall and patient's understanding of the procedure. A
single randomised controlled trial in cardiac surgery showed that audiotaped
consultations improved patient's knowledge of the operation. CONCLUSIONS: Patient
recall and understanding of pre-operative information can significantly improve
with a variety of educational tools. Procedure-specific forms with or without
illustrations as well as interactive multimedia interventions enhance patient
recall and understanding of information. In cardiac surgery patients,
interventions need to meet patients' preferences, be repetitive on crucial points
and consider the nature of the procedure.
PMID- 29937112
TI - What adolescents living with long-term conditions say about being involved in
decision-making about their healthcare: A systematic review and narrative
synthesis of preferences and experiences.
AB - OBJECTIVE: To understand the preferences and experiences of adolescents (age 10
19) with long-term conditions (LTCs) towards involvement in discussions and
decisions regarding management of their condition. METHODS: A systematic review
and narrative synthesis of mixed-methods, quantitative and qualitative and
research was performed. Six databases were searched from inception to March 2017.
The quality of the articles was assessed, and relevant data were extracted and
coded thematically. RESULTS: The search yielded 27 articles which met the
inclusion criteria. Decision-making involvement preferences and experiences were
reported from the adolescents' perspectives. Adolescents often report that they
do not have any choice of treatment options. Variability in preferences and
experiences were found within and between individuals. Mismatches between
preferences and experiences are common, and often with negative emotional
consequences. DISCUSSION: Adolescent preferences for involvement in the decision
making process are situational and individualistic. Healthcare professionals can
encourage involvement by ensuring that adolescents are informed of treatment
options, and aware of the value of their contribution. Future research should
explore adolescent perceived barriers and facilitators to SDM. PRACTICAL
IMPLICATIONS: Interventions are needed to effectively train HCPs in the delivery
of shared decision-making, and to support the participation of adolescents with
LTCs in shared decision-making.
PMID- 29937113
TI - Use of Price Promotions Among U.S. Adults Who Use Electronic Vapor Products.
AB - INTRODUCTION: Sales of electronic vapor products have increased in recent years.
This increase in use may be related to manufacturer price promotions. This study
assessed the use of price-related promotions among current electronic vapor
product users. METHODS: Data from the 2015 and 2016 Summer Styles, an Internet
survey of U.S. adults aged >=18 years, were analyzed in 2017. Current electronic
vapor product users (n=300) were those who reported past 30-day electronic vapor
product use. Price-related promotion use was defined as reported use of coupons,
rebates, discount codes, or other special price-related promotions when
purchasing electronic vapor products (e.g., electronic cigarettes [e-cigarettes],
electronic hookah [e-hookah], or vape pens). Associations between price-related
promotion use and sex, age, race/ethnicity, educational attainment, U.S. region,
cigarette smoking status, electronic vapor product use frequency, place
electronic vapor products were obtained, and survey year were assessed using
multivariable logistic regression. RESULTS: Among current electronic vapor
product users, 15.0% reported using price-related promotions. The adjusted odds
of using price-related promotions was significantly higher among respondents who
obtained electronic vapor products from a gas station, grocery or drug store, or
the Internet (AOR=2.65, 95% CI=1.22, 5.74) versus anywhere else (i.e., mall
kiosks, vape shop, friends/family) and among those who used electronic vapor
products >=15 days in the past 30 days (AOR=2.57, 95% CI=1.18, 5.56) versus <=14
days. CONCLUSIONS: Nearly one in seven current U.S. adult electronic vapor
product users reported using price promotions during 2015-2016, and variations in
price promotion use existed by electronic vapor product use frequency and where
electronic vapor products were obtained. Continued monitoring of the use of price
related promotions could help inform public health policy, planning, and
practice.
PMID- 29937114
TI - Eating, Activity, and Weight-related Problems From Adolescence to Adulthood.
AB - INTRODUCTION: Determining the population-based scope and stability of eating,
activity, and weight-related problems is critical to inform interventions. This
study examines: (1) the prevalence of eating, activity, and weight-related
problems likely to influence health; and (2) the trajectories for having at least
one of these problems during the transition from adolescence to adulthood.
METHODS: Project EAT I-IV (Eating and Activity in Teens and Young Adults)
collected longitudinal survey data from 858 females and 597 males at four waves,
approximately every 5 years, from 1998 to 2016, during the transition from
adolescence to adulthood. Analyses were conducted in 2017-2018. Measures included
high fast-food intake (>=3 times/week), low physical activity (<150
minutes/week), unhealthy weight control, body dissatisfaction, and obesity
status. RESULTS: Among females, the prevalence of having at least one eating,
activity, or weight-related problems was 78.1% at Wave 1 (adolescence) and 82.3%
at Wave 4 (adulthood); in males, the prevalence was 60.1% at Wave 1 and 69.2% at
Wave 4. Of all outcomes assessed, unhealthy weight control behaviors had the
highest prevalence in both genders. The stability of having at least one problem
was high; 60.2% of females and 34.1% of males had at least one problematic
outcome at all four waves. CONCLUSIONS: The majority of young people have some
type of eating, activity, or weight-related problem at all stages from
adolescence to adulthood. Findings indicate a need for wide-reaching
interventions that address a broad spectrum of eating, activity, and weight
related problems prior to and throughout this developmental period.
PMID- 29937115
TI - Biomedical and Behavioral Outcomes of Keep It Up!: An eHealth HIV Prevention
Program RCT.
AB - INTRODUCTION: HIV diagnoses among young men who have sex with men are increasing,
but few effective HIV prevention interventions exist for this population. An RCT
was conducted of the online Keep It Up! intervention to determine if it
significantly reduced condomless anal sex and sexually transmitted infections
compared with an HIV knowledge condition. STUDY DESIGN: From May 2013 to March
2017, a total of 901 participants were enrolled in a double-blinded RCT of Keep
It Up! with 1-year follow-up. After completing baseline surveys and sexually
transmitted infection testing, participants were randomized by an eHealth
platform to the intervention or control condition. SETTING/PARTICIPANTS: HIV
negative men who have sex with men reporting condomless anal sex, aged 18-29
years, were recruited through advertising and from HIV testing sites and outreach
in Atlanta, Georgia; Chicago, Illinois; and New York, New York. INTERVENTION:
Multimedia was used to address HIV knowledge and motivate safer behaviors. The
control condition reflected existing online HIV information. MAIN OUTCOME
MEASURES: Primary outcomes were incident gonorrhea or chlamydia at 12-month
follow-up and self-reported condomless anal sex with casual partners at 3-, 6-,
and 12-month follow-up. RESULTS: In 2017, data were analyzed from 445 (49%)
participants randomized to the intervention and 456 (51%) to the control.
Participants were primarily racial/ethnic minorities (63%). Sexually transmitted
infections at Month 12 was 40% lower for intervention participants (risk
ratio=0.60, 95% CI=0.38, 0.95, p=0.01). For the primary behavioral outcome, both
arms showed reductions over time with 44% of control and 37% of intervention
participants reporting condomless anal sex at Month 12 (prevalence ratio=0.83,
95% CI=0.70, 0.99, p=0.04). CONCLUSIONS: The Keep It Up! intervention resulted in
significantly lower sexually transmitted infection incidence and a small but
significant decrease in condomless anal sex 12 months post-intervention relative
to an online HIV knowledge condition. In addition, this study demonstrated the
feasibility and acceptability of at-home sexually transmitted infection testing
as part of an eHealth intervention. TRIAL REGISTRATION: This study is registered
at www.clinicaltrials.gov NCT01836445.
PMID- 29937116
TI - Effect of lamotrigine on in vivo and in vitro cytokine secretion in murine model
of inflammation.
AB - Alteration in cytokine levels, particularly, IL-6, TNF-alpha, IL-1beta and IL-2,
has been implicated in the pathogenesis of epilepsy and bipolar disorder.
Lamotrigine (LTG), an antiepileptic drug with mood stabilizing properties, has
documented immunomodulatory effects. However, its effect on cytokine secretion in
vivo has not been examined. Besides, studies have reported inconsistent results
of the in vitro effects of LTG on cytokine secretion. Hence, we used murine
models of inflammation to characterize the in vivo and the in vitro effects of
LTG on the secretion of the aforementioned cytokines, using ELISA. LTG
significantly inhibited basal and mitogen-induced IL-6, TNF-alpha and IL-1beta
secretion in vivo and in LPS-treated RAW264.7 cells in vitro. In PMs, LTG
inhibited basal and LPS-induced IL-6 and TNF-alpha secretion. Our findings extend
the current understanding of the anti-inflammatory properties of LTG and may be
relevant to its role in modulating the immune system in epilepsy and bipolar
disorder.
PMID- 29937117
TI - Bi-cruciate substituting total knee arthroplasty provides varus-valgus stability
throughout the midflexion range.
AB - BACKGROUND: Proper soft tissue balance is crucial for a successful clinical
outcome after total knee arthroplasty (TKA). Bi-cruciate substituting (BCS)-TKA
has been developed to more closely approximate normal knee characteristics. The
purpose of the present study was to evaluate midflexion laxity before and after
BCS-TKA using a navigation system, and assess the correlation between
intraoperative laxity and the maximum flexion angle after surgery. METHODS: Fifty
one knees in 46 patients with osteoarthritis replaced with BCS prosthesis were
assessed. Manual mild passive internal-external rotational and varus-valgus
stress was applied to the knees, and the maximum total laxity was measured
automatically by a navigation system before and after TKA. The correlations with
the range of motion (ROM) were evaluated using Spearman's correlation
coefficients (rho). RESULTS: Internal-external stress assessment revealed no
statistically significant difference at each flexion angle before and after BCS
TKA. In contrast, the varus-valgus stress assessment revealed that BCS-TKA had
significantly decreased varus-valgus laxity from preoperative levels at 20-120
degrees flexion angles. Furthermore, the maximum flexion angle at six months
after surgery significantly correlated with the intraoperative laxity at deep
flexion range. CONCLUSION: BCS-TKA stabilized varus-valgus laxity to better than
preoperative levels at midflexion range.
PMID- 29937119
TI - High-performance liquid chromatographic separation of 8-aminopyrene-1,3,6
trisulfonic acid labeled N-glycans using a functional tetrazole hydrophilic
interaction liquid chromatography column.
AB - 8-Aminopyrene-1,3,6-trisulfonate (APTS) is one of the most frequently used
reagent in capillary electrophoresis. Three sulfonate groups in APTS generate
fast electrophoretic mobilities of derivatized glycans, therefore very suitable
for CE-LIF applications. However, these groups also make separation with
partition chromatography difficult. A novel column for hydrophilic interaction
liquid chromatography (HILIC) with an anionic tetrazole functionalized polymer
based silica was examined for the separation of APTS-labeled glycans derived from
specific glycoproteins. This separation mode has enhanced capability for the size
resolution of neutral and acidic oligosaccharides. In addition, specific glycan
isomers, which are usually difficult to separate with HILIC methods, were also
separated. IgG-derived complex-type glycans that have an isomeric pair of
monogalactosylated glycans, as well as differences in the number of galactose
residues, are separable using this mode. We also utilized this column for the
fractionation of APTS-labeled glycans from porcine thyroglobulin and examined
their migration times with CE by co-migration with a mixture of glycoprotein
glycans. Combinational modes of HILIC and anionic repulsion show promise for the
separation and preparation of glycoprotein-derived glycans labeled with APTS.
PMID- 29937120
TI - Needle-based extraction techniques with protected sorbent as powerful sample
preparation tools to gas chromatographic analysis: Trends in application.
AB - Microextraction techniques are widely applied for sample preparation to gas
chromatographic analysis of target compounds in samples with a complex matrix.
Recently, needle-based microextraction techniques have been developed in order to
improve performance of the extraction. The main advantages of these techniques
are miniaturization, automation, high performance, environmentally friendliness
and on-line coupling with analytical instruments. This review focuses on the
three needle-based microextraction techniques including solid-phase dynamic
extraction (SPDE), in-tube extraction (ITEX) and needle trap device extraction
(NTD). The core of the aforementioned techniques is an extraction phase protected
in the stainless steel needle. The application of the sorbent-protected needle
extraction techniques for the gas chromatographic analysis of environmental,
biological and food samples is discussed. The fundamental aspects and development
over the years are also summarized.
PMID- 29937121
TI - Simulation of elution profiles in liquid chromatography - III. Stationary phase
gradients.
AB - A previously developed liquid chromatographic simulator (see parts I and II) [1
3] is extended to allow for simulations of stationary phase gradients with
isocratic and gradient mobile phases. Gradient stationary phases have recently
been proposed as means of engineering unique chromatographic selectivities. In
the present work, the simulator provides retention times and peak widths that
agree with closed form theory for a linear gradient in retention factor and
provides accurate retention time predictions for experimentally implemented
continuous and discontinuous gradients. Calculation of discontinuous gradients
implemented using the commercially available POPLC system have shown good
agreement with experiment, with the largest deviation of the simulated retention
time from experiment of 4.5%. In addition, simulations of a novel continuous
amine gradient column show good agreement with experiment, and give insights into
synergistic interactions on column. With the exception of solutes that show
evidence of synergistic interactions, the simulated retention times are in
agreement with the 95% confidence limits of the experimental values.
PMID- 29937122
TI - Periodic mesoporous organosilica materials as sorbents for solid-phase extraction
of drugs prior to simultaneous enantiomeric separation by capillary
electrophoresis.
AB - Two novel periodic mesoporous organosilica materials were synthesized with a
neutral phenylene-bridged ligand, 1,4-bis(trimethoxysilylethyl)benzene, one of
them using tetraethyl orthosilicate as additional silica source (PMO-TMSEB-1 and
PMO-TMSEB-2). A third material was also synthesized with 1,4
bis(triethoxysilyl)benzene ligand (PMO-TESB-1) which use has scarcely been
reported. The three materials were evaluated as solid-phase extraction (SPE)
sorbents for the off-line extraction of a mixture of seven drugs of different
nature (duloxetine, terbutaline, econazole, propranolol, verapamil, metoprolol,
and betaxolol) from water samples. Subsequent simultaneous enantiomeric analysis
by CE, using sulfated-beta-cyclodextrin (2% w/v) dissolved in a 25 mM phosphate
buffer (pH 3.0) and a voltage of -20 kV (negative polarity) was carried out.
Enantiomeric resolutions ranging from 2.4 to 8.5 were obtained in an analysis
time of 16 min. After optimization of SPE parameters, it was shown that using
just 100 mg of PMO-TESB-1 as sorbent, a preconcentration factor of 400 with 200
mL solution was achieved, allowing recoveries between 80.5 and 103.1% (except for
terbutaline), with good repeatability (% RSD = 2-8 %, n = 5). Analytical
characteristics of the method were evaluated in terms of precision, linearity and
accuracy with method quantitation limits between 5.6 and 21.9 MUg/L. The
developed method was applied to the analysis of spiked wastewater samples
collected in different treatment plants, with recoveries between 73.9 and 102.9%
except for econazole with recovery values ranging between 58.5 and 72.4%.
PMID- 29937124
TI - Editorial.
PMID- 29937123
TI - Thorough study of persistent organic pollutants and halogenated natural products
in sperm whale blubber through preparative sample cleanup followed by
fractionation with countercurrent chromatography.
AB - Marine mammals are top predators of the marine food chain and thus known to
bioaccumulate high concentrations of polyhalogenated compounds. Yet, details of
the organohalogen pattern are largely unknown. For this reason, we isolated the
polyhalogenated compounds from 750 g blubber of a sperm whale (Physeter catodon),
which deceased at the German North Sea coast in January 2016. The sample matrix
was decomposed by sulfuric acid treatment and the polyhalogenated compounds were
then fractionated by countercurrent chromatography (CCC). Seventy-three CCC
fractions were taken and analyzed by gas chromatography with electron capture
negative ion mass spectrometry (GC/ECNI-MS). The bulk of the polyhalogenated
compounds in the sample originated from classic persistent organic pollutants
(POPs). Altogether 90 polychlorinated biphenyl (PCB) congeners were detected in
the sample including all possible octa- to decachloro congeners except one. The
sample also featured 105 toxaphene congeners including 30 chlorobornenes
(contribution ~14% of the total toxaphene content) which were only detected after
the CCC fractionation. In addition, several chlordane and mirex related compounds
were detected which were never or very scarcely described before in biota.
Classic POPs (PCBs, DDT, toxaphene, chlordane, mirex) were predominant, while new
emerging contaminants were scarcely detected. The sample featured several
halogenated natural products (HNPs) some of which were less stable and destroyed
during the sample cleanup involving treatment with sulfuric acid. Sample
fractionation by means of CCC was crucial for the detection and assignment of
many of the uncommon polyhalogenated compounds.
PMID- 29937125
TI - Steps, duration and intensity of usual walking practice during subacute
rehabilitation after stroke: an observational study.
AB - BACKGROUND: Duration of therapy time is an inadequate indicator of stroke
rehabilitation. Steps, duration, and intensity of active therapy time may provide
a better indicator of practice. OBJECTIVE: This study quantified usual walking
practice in terms of steps, duration and intensity of active therapy time, and
distance walked during physical therapy sessions in people with sub-acute stroke
undertaking inpatient rehabilitation and to examine whether usual walking
practice differed depending on walking ability. METHODS: A prospective
observational study was conducted across two metropolitan rehabilitation units in
Australia. Twenty-four stroke survivors were observed over three physical therapy
sessions. Walking ability was categorized as unassisted or assisted based on Item
5 of the Motor Assessment Scale. Walking practice was categorized as basic or
advanced. Steps, duration, intensity and distance walked were measured during
physical therapy sessions. RESULTS: Overall, participants took 560 steps (SD 309)
over 13min (SD 6) at an intensity of steps 44 steps/min (SD 17) and walked 222m
(SD 143) in physical therapy. Unassisted walkers (n=6, 25%) undertook more (or
trended towards more) practice of advanced walking than assisted walkers in terms
of steps (MD 254 steps, 95% CI 48-462), duration (MD 5min, 95% CI 0-10),
intensity (MD 18steps/min, 95% CI -8 to 44) and distance (MD 112m, 95% CI -12 to
236). CONCLUSION: Stroke survivors undergoing inpatient rehabilitation spent
approximately 20% of physical therapy actively engaged in walking practice. Those
able to walk without assistance took more steps for longer, at a higher
intensity. TRIAL REGISTRATION: ACTRN12613000764730
(https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364545).
PMID- 29937126
TI - Unusual Radiographic Presentation of Primary Ewing Sarcoma of the Orbit.
PMID- 29937127
TI - Multimodal Imaging to Monitor Recurrent Serpiginous Choroiditis.
PMID- 29937128
TI - Discriminating the Function(s) of Guard Cell ALMT Channels.
AB - It has been demonstrated that ALMT (ALUMINUM-ACTIVATED MALATE TRANSPORTER)
channels are important players during stomatal movements. Previous investigations
on ALMT family members indicated possible redundancy at the guard cell tonoplast;
however, compelling evidence has recently suggested regulatory mechanisms and
individual roles for specific ALMT proteins in response to diverse environmental
stimuli.
PMID- 29937129
TI - Collateral circulation after thrombosis of the superior vena cava and digestive
hemorrhage.
PMID- 29937130
TI - Thromboembolic disease in orthopaedic surgery and non-surgical trauma.
PMID- 29937131
TI - Intercondylar and central regions of complete discoid lateral meniscus have
different cell and matrix organizations.
AB - BACKGROUND: A complete discoid lateral meniscus (DLM) has a high risk of
horizontal tear. However, cellular phenotypes and extracellular matrix
organizations in complete DLMs are still unclear. The aim of this study was to
investigate histological and cellular biological characteristics in both the
intercondylar and central regions of complete DLM. MATERIALS AND METHODS:
Meniscal samples were obtained from the intercondylar and central regions of
complete DLM (n = 6). Blood vessels and aggregated cell ratio were measured in
each region. Depositions of type I/II collagens and safranin O-stained
proteoglycans in the extracellular matrix were assessed. Experiments in gene
expression, morphology, proliferation, and effect of mechanical stretch were
performed using cultured cells derived from each region. RESULTS: Blood vessel
counts were significantly higher in the intercondylar region than in the central
region. The ratio of aggregated cells was lower in the intercondylar region than
in the central region. Deposition of type I collagen was comparable for both
regions. The central region contained a larger quantity of type II collagen and
safranin O staining density compared with the intercondylar region. Proliferation
of the fibroblastic intercondylar cells was not affected by 5%-stretching.
However, stretching treatments decreased relative proliferation of the
chondrocytic central cells. CONCLUSIONS: This study demonstrated that the central
region of complete DLM had different cellular properties and collagen components
compared with the intercondylar region. Our results suggest that the central
region of complete DLM may have a low healing potential like the inner avascular
region of the meniscus.
PMID- 29937132
TI - Accuracy of powered surgical instruments compared with manual instruments for
pedicle screw insertion: Evaluation using o-arm-based navigation in scoliosis
surgery.
AB - BACKGROUND: Though powered surgical instruments for pedicle screw insertion
combined with navigation have been developed to reduce time taken for spine
surgery, clinical evidence demonstrating the safety and effectiveness of powered
surgical instruments is limited. The goals of the present study were to compare
the accuracy of powered instruments and manual instruments using O-arm-based
navigation in surgery for scoliosis. METHODS: We retrospectively identified 60
consecutive patients with adolescent idiopathic scoliosis who underwent posterior
corrective surgery using O-arm based navigation, collected from Jun 2013 to Feb
2015. Overall, 393 screws were tapped and inserted in 30 patients using manual
instruments (group M) and 547 screws were tapped and inserted in 30 patients
using powered instruments (group P). Postoperative computed tomography was used
to assess screw accuracy using the established Neo classification (Grade 0, no
perforation; Grade 1, perforation <2 mm, Grade 2: perforation >=2 and <4 mm,
Grade 3: perforation >=4 mm). The time to position one screw, including
registration, was calculated. RESULTS: In group M, 331 (84%) of the 393 pedicle
screw placements were categorized as Grade 0, 49 (13%) were Grade 1, 13 (3.3%)
were Grade 2, and 0 were Grade 3. In group P, 459 (84%) of the 547 pedicle screw
placements were categorized as Grade 0, 75 (14%) were Grade 1, 13 (2.4%) were
Grade 2, and 0 were Grade 3. We found no significant difference in the prevalence
of Grade 2-3 perforations between groups. The time to insert one pedicle screw
was 5.4 +/- 1.4 min in group M, but significantly decreased to 3.4 +/- 1.2 min in
group P. CONCLUSIONS: Our results demonstrate that powered instruments using O
arm navigation insert pedicle screws as accurately as conventional manual
instruments using O-arm navigation. The use of powered instruments requires less
time in O-arm surgery for scoliosis.
PMID- 29937134
TI - Frequency, characterization and genotypic analysis of Shiga toxin-producing
Escherichia coli in beef slaughterhouses of Argentina.
AB - The objectives of this study were: (1) to estimate STEC frequency in hide and
carcass samples taken from beef slaughterhouses supplying the domestic market in
Argentina, (2) to establish the pheno-genotypic characteristics of STEC and non
toxigenic Escherichia coli of serogroups O26, O45, O103, O121, O111, O145 or O157
isolated from the analyzed samples and, (3) to study their clonal relatedness.
Sixty hides and 60 carcasses were analyzed. At the screening step, 48% of hide
and 80% of carcass samples tested positive for the stx gene by endpoint PCR. The
STEC isolation rate was 5% for hides and 8% for carcasses. The isolation rate of
STEC-positive for O26, O45, O103, O111, O145 or O157 serogroups was 0% for hides
and 2% for carcasses. With the purpose of studying the clonal relatedness of
isolates, macrorestriction fragment analysis by pulsed-field gel electrophoresis
was performed. The results indicated cross-contamination between hides and
between carcasses of animals in the same lot and, that the origin of carcass
contamination was their own hide, or the hides of other animals in the same lot.
The high detection rate at the screening step, especially in carcasses, and the
evidence of cross-contamination show the need to apply additional in-plant
intervention strategies aimed at preventing carcass contamination.
PMID- 29937133
TI - Medical costs attributable to overweight and obesity in Japanese individuals.
AB - OBJECTIVE: We aimed to reveal the association between body mass index (BMI) and
medical costs in the current Japanese population, and to estimate the population
attributable fraction (PAF) of medical costs due to overweight and obesity.
METHODS: A generalized linear mixed model with log link function and gamma
distribution was used to evaluate the association between BMI and medical costs
in 34,537 beneficiaries of the National Health Insurance aged 40-69 years in
Chiba City. Medical cost data were obtained from insurance claims submitted
between April 2012 and March 2016. PAFs due to overweight (BMI >=25.0 and
<30.0kg/m2) and obesity (BMI >=30.0kg/m2) were calculated. RESULTS: Overweight
and obesity were significant predictors of excessive medical costs in all age and
sex groups. PAF due to overweight and obesity was estimated to be 9.62% (95%
confidence interval, 8.52-10.73%). Additionally, PAFs in 40-59-year-old
individuals (12.76% in men and 11.63% in women) were greater than those in 60-69
year-old subjects (6.55% in men and 7.80% in women) for both sexes. CONCLUSIONS:
In the Japanese population, overweight and obesity are an excessive financial
burden with an estimated PAF of 9.62% of total medical costs.
PMID- 29937135
TI - Endometrial Biopsy in an Outpatient Gynaecological Setting: Overinvestigation.
AB - OBJECTIVE: We reviewed the indications for endometrial biopsy at the general
gynaecology outpatient clinic of the Universite de Montreal Hospital Center and
measured their compliance with the Society of Obstetricians and Gynaecologists of
Canada and other international guidelines. METHODS: Three hundred and seventy-one
files of patients who had an endometrial biopsy between January and October 2015
were reviewed. Indication for endometrial biopsy and pathology results were
noted. Files were separated into four categories. RESULTS: In the postmenopausal
bleeding category, all files complied with the SOGC. We found hyperplasia or
neoplasia in 13% of patients. In the asymptomatic endometrial thickening
category, 9% of the files did not show sufficient indication for biopsy. None of
the patients presented hyperplasia or neoplasia. In the abnormal uterine bleeding
(AUB) - under 41 years old category, there was no indication for biopsy in 23% of
the files. We found hyperplasia or neoplasia in 13% of patients, but only in
patients with an indication for biopsy. In patients with AUB - over 40, non
compliance with SOGC was 3%. But according to international guidelines, 42% of
patients with AUB between 41 and 45 years old did not have an indication for
biopsy and none showed hyperplasia or neoplasia. CONCLUSION: We demonstrated
clinically significant overinvestigation in patients with AUB. Indications should
be reviewed carefully before performing an endometrial biopsy in women under 41.
In addition, the value of endometrial biopsies in patients between 41 and 45
years old with menorrhagia and no additional risk factor should be reevaluated.
PMID- 29937136
TI - Use of Cytomegalovirus-Specific Hyperimmunoglobulins in Pregnancy: A
Retrospective Cohort.
AB - OBJECTIVE: There is no consensus on the use of cytomegalovirus (CMV)-specific
hyperimmunoglobulins (CSHIGs) for suspected congenital CMV infections during
pregnancy, but this therapy is currently used in some countries. The objectives
of this study were to describe tolerability and pregnancy outcome following
treatment with monthly intravenous CSHIG and compare rates of positive PCR and
postnatal symptoms according to whether CSHIGs were given or not. METHODS: This
retrospective cohort study included all pregnant women who were diagnosed with
primary CMV infection or congenital CMV infection at the Centre Hospitalier
Universitaire Sainte-Justine (Montreal, QC) between 2005 and 2016. CSHIG was
discussed with pregnant women who received positive CMV PCR results from amniotic
fluid or if ultrasound anomalies suggested congenital infection and there was
serologic evidence of maternal primary infection (therapeutic group). CSHIG was
also offered as prophylaxis in pregnant women without fetal ultrasound anomalies
but with evidence of maternal primary infection, when amniocentesis either had
negative results or was not performed (prophylactic group). A matched analysis
was performed to control for timing of maternal infection, amniocentesis, and
type and timing of ultrasound anomaly. RESULTS: Sixteen women received CSHIG, and
55 had no CMV-specific treatment. CSHIG treatment was well-tolerated. In
bivariate analyses, the risk of congenital CMV infection and postnatal symptoms
did not significantly decrease with CSHIG treatment, in both the therapeutic and
the prophylactic groups. After matching, there was still no difference in
outcomes between CSHIG-treated and untreated women. CONCLUSION: The effectiveness
of CSHIG in preventing congenital CMV infection and its clinical manifestations
could not be demonstrated.
PMID- 29937137
TI - The effect of dulaglutide on body composition in type 2 diabetes mellitus
patients on hemodialysis.
AB - AIMS: To evaluate the effect of dulaglutide on body composition in type 2
diabetes mellitus (T2DM) patients undergoing hemodialysis (HD). METHODS: Twenty
one T2DM patients on HD, who had been treated with insulin and newly added
teneligliptin (N = 10) or dulaglutide (N = 11), were enrolled. Body composition
changes, such as fat mass (FM) and skeletal muscle mass (SMM), glycated albumin
(GA), and insulin doses were compared before and after six months of treatment
with teneligliptin or dulaglutide. RESULTS: The percentage changes of GA and
insulin doses were comparable between the teneliglipin and dulaglutide groups.
Conversely, although FM and SMM did not change in the teneligliptin group (from
15.7 kg to 14.1 kg, P = 0.63 and 18.6 kg to 18.9 kg, P = 0.16, respectively),
those in the dulaglutide group significantly decreased (from 21.9 kg to 18.9 kg,
P = 0.037 and 21.0 kg to 20.2 kg, P = 0.011, respectively). CONCLUSIONS: Six
months of dulaglutide treatment significantly reduced not only FM but also SMM,
although changes in GA and insulin doses were comparable with those in the
teneligliptin group. Dulaglutide may have the effect of promoting sarcopenia;
therefore, it may be carefully used in T2DM patients on HD.
PMID- 29937138
TI - Lower objectively measured physical activity is linked with perceived risk of
hypoglycemia in type 1 diabetes.
AB - AIMS: Compare physical activity (PA) levels in adults with and without type 1
diabetes and identify diabetes-specific barriers to PA. METHODS: Forty-four
individuals with type 1 diabetes and 77 non-diabetic controls in the Coronary
Artery Calcification in Type 1 Diabetes study wore an accelerometer for 2 weeks.
Moderate-to-vigorous physical activity (MVPA) was compared by diabetes status
using multiple linear regression. The Barriers to Physical Activity in Type 1
Diabetes questionnaire measured diabetes-specific barriers to PA, and the Clarke
hypoglycemia awareness questionnaire measured hypoglycemia frequency. RESULTS:
Individuals with type 1 diabetes engaged in less MVPA, fewer bouts of MVPA, and
spent less time in MVPA bouts per week than individuals without diabetes (all p <
0.05), despite no difference in self-reported PA (p > 0.05). The most common
diabetes-specific barrier to PA was risk of hypoglycemia. Individuals with
diabetes reporting barriers spent less time in MVPA bouts per week than those not
reporting barriers (p = 0.047). CONCLUSIONS: Individuals with type 1 diabetes
engage in less MVPA than those without diabetes despite similar self-reported
levels, with the main barrier being perceived risk of hypoglycemia. Adults with
type 1 diabetes require guidance to meet current PA guidelines and reduce
cardiovascular risk.
PMID- 29937139
TI - Role of plasma glucose level on myocardial perfusion in ST-segment elevation
myocardial infarction patients.
AB - AIMS: Hyperglycemia is frequent in patients with ST elevation myocardial
infarction (STEMI) and is associated with adverse outcome. Aim of our study was
to evaluate the correlation between admission plasma glucose level (PGL) and
coronary arteries flow velocity. METHODS: We enrolled 149 STEMI patients
successfully treated with primary percutaneous coronary intervention (pPCI). The
study population was divided into two groups based on PGL (< or >140 mg/dl) and
on history of diabetes, and the groups compared in terms of corrected TIMI frame
count (cTFC). RESULTS: Hyperglycemic patients had a significantly higher cTFC in
both the culprit (p < 0.0001) and non-culprit vessel (p: 0.0002); diabetes
history impairs as well cTFC of the culprit (p < 0.0001) and non-culprit vessel
(p: 0.0001). Within the subpopulation of diabetic patients hyperglycemic ones
showed higher cTFC in both the culprit (p 0.0013) and non-culprit vessel (p:
0.0006). Moreover in the whole population cTFC values of both arteries increase
linearly with the increment of admission PGL. CONCLUSIONS: Admission PGL affects
coronary flow of both culprit and non-culprit vessel. The impairment of coronary
flow is also demonstrated in known diabetic patients, suggesting to consider
hyperglycemia an additional risk factor. We finally demonstrated for the first
time a positive linear relationship between PGL and cTFC.
PMID- 29937140
TI - Introduction to the SSIB 2017 Annual Meeting Special Issue.
PMID- 29937141
TI - Sleep frequently asked questions: Question 1: What abnormalities do babies with
cleft lip and/or palate have on polysomnography?
PMID- 29937142
TI - High Expression of CD200 and CD200R1 Distinguishes Stem and Progenitor Cell
Populations within Mammary Repopulating Units.
AB - Aiming to unravel the top of the mammary epithelial cell hierarchy, a subset of
the CD49fhighCD24med mammary repopulating units (MRUs) was identified by flow
cytometry, expressing high levels of CD200 and its receptor CD200R1. These
MRUCD200/CD200R1 repopulated a larger area of de-epithelized mammary fat pads
than the rest of the MRUs, termed MRUnot CD200/CD200R1. MRUCD200/CD200R1
maintained a much lower number of divergently defined, highly expressed genes and
pathways that support better cell growth, development, differentiation, and
progenitor activity than their MRUnot CD200/CD200R1 counterparts. A defined
profile of hierarchically associated genes supporting a single-lineage hypothesis
was confirmed by in vitro mammosphere analysis that assembled 114 genes with
decreased expression from MRUCD200/CD200R1 via MRUnot CD200/CD200R1 toward
CD200+CD200R1- and CD200R1+CD200- cells. About 40% of these genes were shared by
a previously published database of upregulated genes in mammary/breast stem cells
and may represent the core genes involved in mammary stemness.
PMID- 29937143
TI - ICAM-1 Deficiency in the Bone Marrow Niche Impairs Quiescence and Repopulation of
Hematopoietic Stem Cells.
AB - The bone marrow niche plays a critical role in controlling the fate of
hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals.
However, the molecular events in the HSC niche remain to be investigated. Here,
we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC
quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1
/-) displayed significant expansion of phenotypic long-term HSCs with impaired
quiescence, as well as favoring myeloid cell expansion. ICAM-1-deficient HSCs
presented normal reconstitution capacity during serial transplantation; however,
reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche
impaired HSC quiescence and repopulation capacity. In addition, ICAM-1 deletion
caused failure to retain HSCs in the bone marrow and changed the expression
profile of stroma cell-derived factors, possibly representing the mechanism for
defective HSCs in ICAM-1-/- mice. Collectively, these observations identify ICAM
1 as a regulator in the bone marrow niche.
PMID- 29937144
TI - Disruption of GRIN2B Impairs Differentiation in Human Neurons.
AB - Heterozygous loss-of-function mutations in GRIN2B, a subunit of the NMDA
receptor, cause intellectual disability and language impairment. We developed
clonal models of GRIN2B deletion and loss-of-function mutations in a region
coding for the glutamate binding domain in human cells and generated neurons from
a patient harboring a missense mutation in the same domain. Transcriptome
analysis revealed extensive increases in genes associated with cell proliferation
and decreases in genes associated with neuron differentiation, a result supported
by extensive protein analyses. Using electrophysiology and calcium imaging, we
demonstrate that NMDA receptors are present on neural progenitor cells and that
human mutations in GRIN2B can impair calcium influx and membrane depolarization
even in a presumed undifferentiated cell state, highlighting an important role
for non-synaptic NMDA receptors. It may be this function, in part, which
underlies the neurological disease observed in patients with GRIN2B mutations.
PMID- 29937145
TI - TGF-beta1 Negatively Regulates the Number and Function of Hematopoietic Stem
Cells.
AB - Transforming growth factor beta1 (TGF-beta1) plays a role in the maintenance of
quiescent hematopoietic stem cells (HSCs) in vivo. We asked whether TGF-beta1
controls the cell cycle status of HSCs in vitro to enhance the reconstitution
activity. To examine the effect of TGF-beta1 on the HSC function, we used an in
vitro culture system in which single HSCs divide with the retention of their
short- and long-term reconstitution ability. Extensive single-cell analyses
showed that, regardless of its concentration, TGF-beta1 slowed down the cell
cycle progression of HSCs but consequently suppressed their self-renewal
potential. Cycling HSCs were not able to go back to quiescence with TGF-beta1.
This study revealed a negative role of TGF-beta1 in the regulation of the HSC
number and reconstitution activity.
PMID- 29937146
TI - Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic
Lineages of Adult Mouse Skeletal Progenitors.
AB - Bone, cartilage, and marrow adipocytes are generated by skeletal progenitors, but
the relationships between lineages and mechanisms controlling their
differentiation are poorly understood. We established mouse clonal skeletal
progenitors with distinct differentiation properties and analyzed their
transcriptome. Unipotent osteogenic and adipogenic cells expressed specific
transcriptional programs, whereas bipotent clones combined expression of those
genes and did not show a unique signature. We tested potential regulators of
lineage commitment and found that in the presence of interferon-gamma (IFNgamma)
adipogenic clones can be induced to osteogenesis and that their adipogenic
capacity is inhibited. Analysis of IFNgamma-regulated genes showed that lineage
signatures and fate commitment of skeletal progenitors were controlled by EGR1
and EGR2. Knockdown experiments revealed that EGR1 is a positive regulator of the
adipogenic transcriptional program and differentiation capacity, whereas EGR2
inhibits the osteogenic program and potency. Therefore, our work revealed
transcriptional signatures of osteogenic and adipogenic lineages and mechanism
triggering cell fate.
PMID- 29937147
TI - OCIAD1 Controls Electron Transport Chain Complex I Activity to Regulate Energy
Metabolism in Human Pluripotent Stem Cells.
AB - Pluripotent stem cells (PSCs) derive energy predominantly from glycolysis and not
the energy-efficient oxidative phosphorylation (OXPHOS). Differentiation is
initiated with energy metabolic shift from glycolysis to OXPHOS. We investigated
the role of mitochondrial energy metabolism in human PSCs using molecular,
biochemical, genetic, and pharmacological approaches. We show that the carcinoma
protein OCIAD1 interacts with and regulates mitochondrial complex I activity.
Energy metabolic assays on live pluripotent cells showed that OCIAD1-depleted
cells have increased OXPHOS and may be poised for differentiation. OCIAD1
maintains human embryonic stem cells, and its depletion by CRISPR/Cas9-mediated
knockout leads to rapid and increased differentiation upon induction, whereas
OCIAD1 overexpression has the opposite effect. Pharmacological alteration of
complex I activity was able to rescue the defects of OCIAD1 modulation. Thus,
hPSCs can exist in energy metabolic substates. OCIAD1 provides a target to screen
for additional modulators of mitochondrial activity to promote transient
multipotent precursor expansion or enhance differentiation.
PMID- 29937148
TI - Intuitive Assessment of Mortality Based on Facial Characteristics: Behavioral,
Electrocortical, and Machine Learning Analyses.
AB - Studies of various characteristics of the human face indicate that it contains a
wealth of information about health status. Most studies involve objective
measurement of facial features as correlated with historical health information.
But some individuals also claim to be adept at intuitively gauging mortality
based solely upon a quick glance at a person's photograph. To test this claim, we
invited 12 such individuals to see if they could tell if a person was alive or
dead based solely on a brief examination of his or her photograph. All photos
used in the experiment were transformed into a uniform gray scale and
counterbalanced across eight categories as follows: gender, age, gaze direction,
glasses, head position, smile, hair color, and image resolution. Participants
examined 404 photographs displayed on a computer monitor, one photo at a time,
each shown for a maximum of 8seconds. Half of the individuals in the photos were
deceased, and half were alive at the time the experiment was conducted.
Participants were asked to indicate if they thought the person in a photo was
living or deceased by pressing an appropriate button. Overall, mean accuracy on
this task was 53.6%, where 50% was expected by chance (P = .005, two tail).
Statistically significant accuracy was independently obtained in 5 of the 12
participants. We also collected 32-channel electrocortical recordings and
observed a robust difference between images of deceased individuals correctly vs.
incorrectly classified in the early event related potential at 100ms post
stimulus onset. We then applied machine learning techniques to classify the
photographs based on 11 image characteristics; both random forest and logistic
regression machine learning approaches were used, and both classifiers failed to
achieve accuracy above chance level. Our results suggest that some individuals
can intuitively assess mortality based on some as-yet unknown features of the
face.
PMID- 29937149
TI - Corrigendum to "AHR and CYP1A expression link historical contamination events to
modern day development in the American alligator" [Environ. Pollut. 230 (2017)
1050-1061].
PMID- 29937150
TI - Outcomes of the TrapEase inferior vena cava filter over 10 years at a single
health care system.
AB - PURPOSE: To retrospectively investigate the safety, efficacy, and complications
associated with TrapEase inferior vena cava filters. METHODS: All patients who
received a TrapEase filter at a single institution between April 2003 and January
2013 were identified, and outcomes were reviewed and analyzed. RESULTS: During
the study period, 594 patients (278 women; mean age, 68.9 +/- 13.6 years; range,
19.2-96.3 years) received a TrapEase filter. The duration of this study was 88
months, with a median clinical follow-up of 3.6 months (range, 0-148.3 months).
During follow-up, 489 of 594 patients (82.3%) died and 105 remained alive with
filters in situ. Nine cases of breakthrough pulmonary embolism occurred among the
582 patients with clinical follow-up (1.5%). Among 128 patients with imaging that
contained the filter, there were 17 cases of filter fracture (13.3%). Of the 39
patients with available computed tomography scans, eight had filling defects
within the filter suggestive of thrombus or embolus (20.5%), including two
patients with complete caval occlusion. Recurrent deep vein thrombosis occurred
in 109 out of 582 patients (18.7%) with clinical follow-up. CONCLUSIONS: Most
patients who received TrapEase filters died during follow-up, possibly because
operators chose to implant a permanent filter in patients with known terminal
illnesses. The filter fracture rate seemed to be high, but there were no
instances of free fracture fragment or distant migration. Although the filter may
theoretically be effective in preventing thrombus migration owing to the double
basket design, pulmonary embolism breakthrough rates were comparable with rates
seen with other filters.
PMID- 29937151
TI - Convulsive status epilepticus management in adults and children: Report of the
Working Group of the Polish Society of Epileptology.
AB - INTRODUCTION: The Working Group was established at the initiative of the General
Board of the Polish Society of Epileptology (PSE) to develop an expert position
on the treatment of convulsive status epilepticus (SE) in adults and children in
Poland. Generalized convulsive SE is the most common form and also represents the
greatest threat to life, highlighting the importance of the choice of appropriate
therapeutic treatment. AIM OF GUIDELINE: We present the therapeutic options
separately for treatment during the early preclinical (>5-30min), established (30
60min), and refractory (>60min) SE phases. This division is based on time and
response to AEDs, and indicates a practical approach based on pathophysiological
data. RESULTS: Benzodiazepines (BZD) are the first-line drugs. In cases of
ineffective first-line treatment and persistence of the seizure, the use of
second-line treatment: phenytoin, valproic acid or phenobarbital is required. SE
that persists after the administration of benzodiazepines and phenytoin or
another second-line AED at appropriate doses is defined as refractory and drug
resistant and requires treatment in the intensive care unit (ICU). EEG monitoring
is essential during therapy at this stage. Anesthesia is typically continued for
an initial period of 24h followed by a slow reversal and is re-established if
seizures recur. Anesthesia is usually administered either to the level of the
"burst suppression pattern" or to obtain the "EEG suppression" pattern.
CONCLUSIONS: Experts agree that close and early cooperation with a neurologist
and anesthetist aiming to reduce the risk of pharmacoresistant cases is an
extremely important factor in the treatment of patients with SE. This report has
educational, practical and organizational aspects, outlining a standard plan for
SE management in Poland that will improve therapeutic efficacy.
PMID- 29937152
TI - Use of combined hormonal contraceptives for the treatment of endometriosis
related pain: a systematic review of the evidence.
AB - OBJECTIVE: To review the available clinical evidence on the use of combined
hormonal contraceptive (CHC) agents (estrogen [E]-progestin combinations) for the
treatment of endometriosis-related pain. DESIGN: A systematic review of the
MEDLINE, Embase, and Derwent Drug File databases for prospective clinical
studies. SETTING: Not applicable. PATIENT(S): Women with endometriosis diagnosed
by validated means. INTERVENTION(S): Combined hormonal contraceptive agents,
active comparators, placebo, or no treatment. MAIN OUTCOME MEASURE(S):
Endometriosis-related pain (dysmenorrhea, pelvic pain, and dyspareunia).
RESULT(S): Nine randomized controlled trials and nine observational studies met
the inclusion criteria. The quality of data was low: only two of the nine
randomized trials were placebo controlled, and most trials were not blinded. The
CHC agents were reported to significantly reduce dysmenorrhea, pelvic pain, and
dyspareunia from baseline in most studies; continuous administration seemed to be
more useful than cyclic administration. The effectiveness of CHC agents for pain
reduction was similar to or less than that of oral progestins and GnRH agonists.
CONCLUSION(S): The available literature suggests that CHC treatment is effective
for relief of endometriosis-related dysmenorrhea, pelvic pain, and dyspareunia;
however, the supportive data are of low quality. Furthermore, insufficient data
exist to reach conclusions about the overall superiority of any given CHC
therapy, and the relative benefit in comparison to other approaches. Additional
high-quality studies are needed to clarify the role of CHC agents and other
treatments in women with endometriosis-related pain.
PMID- 29937153
TI - Transvaginal natural orifice transluminal endoscopic surgery tubal reanastomosis:
a novel route for tubal surgery.
AB - OBJECTIVE: To demonstrate how a transvaginal natural orifice transluminal
endoscopic surgery (NOTES) tubal reanastomosis is a novel route for tubal
surgery. The surgical technique is a combination of traditional vaginal surgery
with single-site surgical skills. DESIGN: The surgical technique is explained in
a stepwise fashion with the use of surgical video footage. The video uses a
surgical case to demonstrate the specific techniques necessary to perform a NOTES
tubal reanastomosis. SETTING: Teaching university. PATIENT(S): A 42-year-old
female G2P2 with a history of tubal ligation 11 years before presentation
requesting a tubal recanalization. INTERVENTION(S): Transvaginal NOTES tubal
reanastomosis was initiated with a posterior colpotomy. A single-site gelport was
placed. The fallopian tubes were hydrodissected, the blocked portion of each tube
was removed, an epidural catheter was threaded through each lumen, and the two
remaining segments of each tube were sutured together in an end-to-end fashion
using single-site suturing skills. MAIN OUTCOME MEASURE(S): Transvaginal NOTES
tubal reanastomosis as an alternative route for tubal reanastomosis. RESULT(S):
The bilateral fallopian tubes were recanalized with bilateral tubal patency. This
was confirmed 8 weeks postoperatively with a three-dimensional sonohystogram,
which showed patency of the bilateral fallopian tubes. CONCLUSION(S): The current
preferred technique for reversal of a tubal sterilization is to perform a
minimally invasive surgery with an end-to-end anastomosis. This gives the patient
a 60%-90% intrauterine pregnancy rate postoperatively. NOTES has the benefits of
a fast recovery, no abdominal incisional pain, and an extremely cosmetic outcome.
Current research has shown a 0%-3.1% range for the risk of pelvic infection in
transvaginal NOTES if prophylactic antibiotics are administered during the
surgery. The NOTES tubal reanastomosis combines the traditional vaginal surgery
technique of creating a posterior colpotomy with single-site surgical skills like
suturing and knot tying. The surgery is completed through a single transvaginal
port without an abdominal incision. In the hands of a skilled minimally invasive
surgeon, transvaginal NOTES tubal reanastomosis is a feasible and alternative
route for this procedure.
PMID- 29937154
TI - On how to define and measure SDM.
PMID- 29937155
TI - Letter to the Editor on "The Safety of Tranexamic Acid in Total Joint
Arthroplasty: A Direct Meta-Analysis".
PMID- 29937156
TI - Orbital presentation of Rosai-Dorfman disease.
AB - OBJECTIVE: To report a case of orbital mass and proptosis, diagnosed as Rosai
Dorfman disease (RDD). METHODS: Clinical case report based on the review of
clinical charts, radiological images, and histopathology. RESULTS: A 42-year-old
male with orbital mass and proptosis of the right eye. A surgical biopsy was
performed, and the diagnosis of RDD was established using microscopy and
immunohistochemistry. Definitive management included open tumour cytoreduction,
with good response. DISCUSSION: The RDD is a rare, benign, proliferative
condition of unknown origin. It rarely affects the cranial cavities, with the
orbital presentation being very unusual. Diagnostic confirmation is essential for
the best surgical management.
PMID- 29937157
TI - Response to tocilizumab treatment in Graves' ophthalmopathy by measuring rectus
muscle thickness and chemosis using optical coherence tomography.
AB - PURPOSE: To assess the extraocular muscle thickness and chemosis after treatment
with tocilizumab in patients with active Graves' ophthalmopathy by optical
coherence tomography. METHODS: Case series of five patients with active Graves'
ophthalmopathy (clinical activity score >=4/10) treated with 4 doses of
tocilizumab. These patients had been previously treated with corticosteroids with
no response. Spectral-domain optical coherence tomography was employed to
determine lateral and medial rectus muscle thickness and chemosis before and
after 4 doses of tocilizumab given monthly. Scanning was performed at 3 and 9
o'clock (nasal and temporal). RESULTS: The study included four women and one man
with a median age of 52 years (range: 38-73). Median Graves' ophthalmopathy
activity duration was 17 months (12-18). Median medial rectus and determine
lateral thicknesses pre-treatment were 249MUm (174-366) and 337MUm (142-443),
respectively. Median chemosis was 409MUm (290-610). After tocilizumab treatment,
median muscle thicknesses reduced to 157MUm (88-187) and 197MUm (99-290),
respectively (P=.043; Wilcoxon) and chemosis to 59MUm (0-78). Median clinical
activity score decreased from 5 (4-8) to 1 (0-3). CONCLUSIONS: A reduction in
extraocular muscle thickness and chemosis was observed after treatment with
tocilizumab in Graves' ophthalmopathy patients using an optical coherence
tomography, so this technique could be a useful complementary technique to assess
the therapeutic responses.
PMID- 29937158
TI - Are all patients subject to the same follow-up after type A dissection repair?
PMID- 29937159
TI - A novel combined ex vivo and in vivo lentiviral interleukin-10 gene delivery
strategy at the time of transplantation decreases chronic lung allograft
rejection in mice.
AB - OBJECTIVE: Our objective was to develop a rapid-onset and durable gene-delivery
strategy that is applicable at the time of transplant to determine its effects on
both acute rejection and chronic lung allograft fibrosis using a mouse orthotopic
lung transplant model. METHODS: C57BL/6 mice received an orthotopic left lung
transplant from syngeneic donors or C57BL/10 donors. By using syngeneic lung
transplantation, we established a novel gene transfer protocol with lentivirus
luciferase intrabronchial administration to the donor lung ex vivo before
transplantation. This strategy was applied in allogeneic lung transplantation
with lentivirus engineering expression of human interleukin-10 or lentivirus
luciferase (control). RESULTS: Bioluminescent imaging revealed that the highest
early transgene expression was achieved when lentivirus luciferase was
administered both directly into the donor lung graft ex vivo before implantation
and subsequently to the recipient in vivo daily on post-transplant days 1 to 4,
compared with post-transplant in vivo administration only (days 0 to 4). Our
previous work with adenoviral interleukin-10 gene therapy indicates that early
interleukin-10 expression in the allograft is desirable. Therefore, we selected
the combined protocol for human interleukin-10 encoding lentiviral vector
therapy. In the allogeneic transplant setting, ex vivo and in vivo human
interleukin-10 encoding lentiviral vector therapy reduced acute rejection grade
(2.0 vs 3.0, P < .05) at day 28. The percentage of fibrotic obliterated airways
was reduced in the human interleukin-10 encoding lentiviral vector-treated group
(10.9% +/- 7.7% vs 40.9% +/- 9.3%, P < .05). CONCLUSIONS: Delivery of lentiviral
interleukin-10 gene therapy, using a novel combined ex vivo and in vivo delivery
strategy, significantly improves acute and chronic rejection in the mouse lung
transplant model.
PMID- 29937160
TI - Comparing laparoscopic surgery with open surgery for long-term outcomes in
patients with stage I to III colon cancer.
AB - BACKGROUND: Although the short-term advantages of laparoscopy for colon cancer
(CC) over open surgery have been clearly demonstrated, there is little evidence
available concerning the long-term outcomes. This study aimed to compare the long
term results of laparoscopic surgery versus open surgery in a cohort of CC
patients from a single center. METHODS: A series of 443 patients consecutively
operated on for stage I to III CC between January 2006 and December 2013 were
followed up. Patients were divided into two groups according to the surgical
technique and were compared for disease-free survival (DFS) and overall survival
(OS) before and after 1:1 propensity score matching. RESULTS: Due to exclusions
and drop-outs, the statistical analysis of the study is based on 398 patients.
Open surgery was performed in 133 patients, and laparoscopic surgery was
performed in 265. After propensity score matching, two comparable groups of 89
patients each were obtained. The 5-year DFS was 64.3% and 78.2% for patients in
the open and laparoscopic resection groups, respectively [hazard ratio (HR) 0.63,
95% confidence interval (CI) 0.33-1.19; P = 0.148]. A 5-year OS of 72.1% and
86.8% was observed in the open and laparoscopic resection groups, respectively
(HR 0.43, 95%CI 0.20-0.94; P = 0.026). The multivariate survival analysis
demonstrated better results of laparoscopy compared with open surgery for both
DFS (HR 0.43, 95%CI 0.23-0.78; P = 0.004) and OS (HR 0.28, 95%CI 0.14-0.59; P <
0.001). CONCLUSIONS: Despite the limitations of a retrospective analysis, our
study confirms better results for laparoscopic surgery in terms of DFS and OS
compared with open surgery in CC treatment.
PMID- 29937161
TI - Prognostic impact of perineural invasion in early stage oral tongue squamous cell
carcinoma: Results from a prospective randomized trial.
AB - BACKGROUND: Although perineural invasion (PNI) has been recognized as a poor
prognostic factor for oral cancer, few studies have focused on tongue squamous
cell carcinoma (TSCC). Using a prospective randomized trial, this study
investigated the role of PNI in the regional control and survival of the patients
with cT1-2N0 TSCC, and clarified the benefit of neck management based on PNI
status. METHODS: PNI status was reviewed under H&E staining in tumors of 221
patients with cT1-2N0 TSCC, who were randomly assigned into elective neck
dissection (END) group (n = 111) and observation group (n = 110). Oncologic and
survival outcomes were analyzed by multivariate regression and Kaplan-Meier
analyses. RESULTS: PNI was identified in 34 patients and multivariate analyses
revealed that PNI remained an independent predictor for cervical lymph node
metastasis (CLNM), local relapse, neck relapse and disease-specific survival
(DSS) after controlling for T stage and pathologic differentiation. END could not
improve the benefit for patients. Stratified analysis revealed that END also
could not improve neck control or DSS among patients with PNI. CONCLUSIONS: This
study demonstrated that PNI was an invaluable pathological parameter to
independently predict cervical metastasis, local relapse, neck relapse and poor
survival outcomes, but END could not improve benefits compared to observation for
the PNI-positive patients.
PMID- 29937162
TI - Beyond T, N and M: The impact of tumor deposits on the staging and treatment of
colorectal and gastric carcinoma.
AB - This review aims to describe the results of the most recent studies on the
prognostic value of TDs and highlight the impact of TDs on the staging and
treatment of colorectal and gastric carcinoma. For colorectal carcinoma TDs have
an adverse prognostic effect that is at least similar to that of positive
regional lymph nodes. However, support is growing in favor of including of TDs in
the M category, rather than the N or T categories of the TNM classification.
Moreover, TDs seem to have an adverse effect on outcomes not only in patients
without lymph node involvement but also in patients with nodal involvement.
Although the prognostic impact of TDs in gastric cancer appears to be undeniable,
the actual prognostic determinants of TDs, particularly in relation to the
number, size and histological types, remain to be established. Although the 7th
and 8th Edition of the TNM classification of colorectal and gastric carcinoma
includes TDs in the N category, no current procedures or methods to assess
preoperative or intraoperative N-status allow TD detection. After neoadjuvant
treatment for advanced rectal carcinoma, the presence of TDs may indicate
incomplete eradication of the main tumor and not discontinuous tumor foci. TDs
have an undeniable prognostic impact but no algorithm of staging and strategy of
treatment has been conformed to this prognostic factor to overcome the classical
T,N, and M prognostic categories. Staging and treatment of colorectal and gastric
cancers should be reconsidered in light of the emerging prognostic value of TDs.
PMID- 29937163
TI - Robotic salvage lymph node dissection for nodal-only recurrences after radical
prostatectomy: Perioperative and early oncological outcomes.
AB - BACKGROUND: Salvage lymph node dissection (sLND) - performed open or minimally
invasive - is a treatment modality that can be offered to patients with nodal
recurrence after radical prostatectomy (RP), especially in times where modern
imaging methods like choline- or PSMA-PET/CT are available. Yet, there are only
very limited data on the safety and oncological effectiveness of robotic sLND.
METHODS: We retrospectively identified patients who underwent robotic sLND at our
institution between 2013 and 2017 for nodal recurrence after RP, which had been
diagnosed either by 18F-choline- or 68Ga-PSMA-PET/CT. We analyzed perioperative
data and early oncological outcomes with a focus on the comparison of patients
with preoperative choline- vs. those with preoperative PSMA-PET/CT. RESULTS: We
identified 36 patients who underwent robotic sLND at a median time of 45.3 months
[range 3.1;228.6] after RP, with nodal recurrences detected in 25 patients by
PSMA- and in 11 by choline-PET/CT. Median preoperative PSA, operation time and
blood loss were 1.98 ng/ml [range 0.09;35.15], 129.5 min [range 65;202] and 50 ml
[range 0;400], respectively. No high-grade complications occurred. A median
number of 6.5 [range 1;25] lymph nodes were removed with a median of 1 [range
0;9] tumor-occupied node. None of the patients received any adjuvant treatment.
Median postoperative PSA-change was -57% [range -100; +58] in the PSMA- and +10%
[range -91; +95] in the choline-group (p = 0.015). 44% of patients in the PSMA-
and 18% of patients in the choline-group experienced complete biochemical
response (cBCR; PSA <0.2 ng/ml). Median time from sLND to the initiation of
further therapy was 12 months [range 2;21.5] in the PSMA-group and 4.7 months
[range 2.2;18.9] in the choline-group (p = 0.001). CONCLUSIONS: This is the
hitherto largest series on robotic sLND for nodal recurrence after RP. Robotic
sLND is a feasible therapeutic option with low morbidity, which can at least
delay the initiation of further therapy - in some patients up to several years.
However, the extend of sLND has to be standardized and randomized trials are
needed to finally define the oncological effectiveness of this approach.
PMID- 29937164
TI - External validation of a modified 8th AJCC TNM system for advanced gastric
cancer: Long-term results in southern China.
AB - BACKGROUND: The 8th edition of AJCC TNM staging manual for gastric cancer (GC)
has been validated by several studies. A modified staging system based on it and
total harvested number of lymph nodes (LNs; cutoff: 30) is suggested to improve
predictive capacities for advanced GC. This study is designed to validate the
modified method using a single-center database in Southern China. METHODS:
Clinical data from 684 GC patients with stage II and III according to the 7th
edition between 2001 and 2012 were reviewed. A modified staging system was
applied to restage the cohort. The three staging systems were compared in terms
of prognostic performance on long-term survival. RESULTS: The median follow-up
period of this cohort was 52 (range, 6-180) months, with a median 5-year overall
survival rate of 52.4%. Stage migration was observed in 159 (23.2%) patients
according to the 8th edition of TNM staging, and another migration was observed
in 108 (15.8%) patients according to the modified TNM staging system. Compared
with the modified staging system, both 7th and 8th edition of AJCC TNM staging
systems did not prove survival concordance on stage IIIA (7th edition) and stage
IIIC (8th edition) when <30 LNs were examined. The survival performance between
two AJCC staging systems had no significant improvement (c-index, 0.607 vs.
0.609), with the best prognostic stratification obtained using the modified
staging method (c-index, 0.631). CONCLUSIONS: The modified staging system on
basis of the 8th AJCC classification and the number of harvested LNs could
provide an optimal predictive capacities for advanced gastric cancer.
PMID- 29937165
TI - Psoas/iliacus muscle invasion from mucinous appendiceal neoplasm. Radiologic
appearance and outcome of treatment in 3 patients.
AB - BACKGROUND: Mucinous appendiceal neoplasms have a pattern of metastases that is
different from the other gastrointestinal cancers. The first site for cancer
dissemination is the peritoneal space surrounding the primary tumor and this is
followed by increasingly extensive peritoneal spread. Invasion of the psoas and
iliacus muscle is an unusual phenomenon. METHOD: From a prospective database of
appendiceal mucinous neoplasms treated by cytoreductive surgery (CRS) and
perioperative hyperthermic chemotherapy (HIPEC), patients with psoas muscle
invasion were reviewed. Their clinical features and treatments were tabulated.
RESULTS: Three patients with ages 33, 60, and 63 were identified. Two patients
had disease progression into the psoas muscle 33 and 95 months after CRS plus
HIPEC. One had dissecting mucinous tumor into psoas, iliacus and quadratus
lumborum muscle at the time of diagnosis of the appendiceal mucinous neoplasm.
All three survived at least five years from their initial treatment. CONCLUSION:
Despite the fact that mucinous tumor invasion was outside the peritoneal cavity,
long term benefit from psoas muscle resection with a mucinous appendiceal
neoplasm is possible and resection possibly with HIPEC should be considered.
PMID- 29937166
TI - Risk scoring system for predicting axillary response after neoadjuvant
chemotherapy in initially node-positive women with breast cancer.
AB - BACKGROUND: One of the current therapeutic challenges for women with breast
cancer receiving neoadjuvant chemotherapy (NAC) is distinguishing women with
complete axillary nodal response from those with axillary residual disease to
promote a personalized therapeutic strategy including sparing axillary surgery.
This study set out to develop a risk scoring system (RSS) for predicting
probability of nodal pathological complete response (pCR) in women presenting
with cN1 breast cancer who received NAC. METHODS: Data of 116 women with cN1
breast cancer who received NAC between January 2009 and December 2013 were
abstracted from our prospectively maintained database. A risk model based on
factors impacting nodal axillary was developed. RESULTS: The overall nodal
conversion rate was 36.2% (42/116). Axillary nodal response was associated with
three variables: menopausal status [Odds ratio (OR) = 0.23; 95% confidence
interval (CI) 0.09-0.60], the radiological % of breast tumour shrinkage >=50% (OR
= 3.71; 95% CI 1.51-9.10), and negative hormone receptors (ER-, PR-) (OR = 2.41;
95% CI 0.99-5.87). These variables were included in the RSS and assigned scores
ranging from 0 to 2. The discrimination of the RSS was 0.78 [95% confidence
interval (CI) 0.69-0.86]. A total score of 3 points corresponded to the optimal
threshold of the RSS. The diagnostic accuracy was 74.1%. CONCLUSIONS: This study
shows that the probability of axillary nodal pCR after NAC can be accurately
predicted so that women at high probability may be spared of axillary surgery.
PMID- 29937167
TI - The risk of thyroid cancer and obesity: A nationwide population-based study using
the Korea National Health Insurance Corporation cohort database.
AB - INTRODUCTION: In recent years, the incidence of thyroid cancer and obesity has
increased rapidly worldwide. Many studies have been conducted on the relationship
between thyroid cancer and obesity; however, the potential mechanisms are not
well understood, and few studies have been performed in Asia. This study aimed to
identify the relationship between the risk of thyroid cancer and obesity in the
Korean population based on a large cohort of data. METHOD: We analyzed clinical
data from a total of 351,402 individuals (males: 181,709, females: 169,693) aged
over 20 years who received medical examinations arranged by the national
insurance program from 2003 to 2008. Newly diagnosed thyroid cancer was
identified using insurance claims data. The median follow-up duration was 7.01
years. RESULTS: The mean body mass index (BMI) of the subjects was 23.6 +/- 3.2
kg/m2 (males, 24 +/- 3; females, 23.1 +/- 3.3). A total of 3308 individuals
(0.94%) developed thyroid cancer during the study period. The risk of thyroid
cancer was higher with increasing BMI in both men and women. Hazard ratios (95%
confidence interval) for obese (25-29.9 kg/m2) and extremely obese (>=30 kg/m2)
groups were 1.23 (1.13-1.34) and 1.26 (1.02-1.50), respectively, compared to the
normal group (18.5-22.9 kg/m2). In particular, the association between the risk
of thyroid cancer and BMI was more remarkable in the male group than female
group. CONCLUSION: Our findings show that higher BMI is positively associated
with the risk of thyroid cancer. Furthermore, this study supports the positive
association between obesity and the increased incidence of thyroid cancer.
PMID- 29937168
TI - Sonographic features of papillary thyroid microcarcinoma predicting high-volume
central neck lymph node metastasis.
AB - OBJECTIVE: To study the correlations between the sonographic features of
papillary thyroid microcarcinoma (PTMC) and the presence of high-volume lymph
node metastasis. METHOD: Medical records of 2363 PTMC patients were reviewed form
October 2013 to December 2015. All the patients with lymph node metastasis
identified by histopathology were included. Preoperative sonographic features,
such as multifocality, tumour size, echogenicity, calcification, vascularity of
papillary microcarcinoma, and capsule invasion, were recorded. Univariate and
multivariate analyses were performed to investigate the relationships between
sonographic features and high-volume lymph node metastasis (number of metastatic
lymph nodes >5). RESULTS: In total, 152 patients had high-volume central lymph
node metastasis (6.4%, 152/2363). Multiple logistic regression analysis showed
that the preoperative ultrasonic features of microcalcifications (OR = 3.33, p =
0.022), larger tumour size (>7 mm) (OR = 2.802, p < 0.001), and capsule invasion
(OR = 2.141, p = 0.006) were independent risk factors for high-volume lymph node
metastasis in the central compartment of PTMC. CONCLUSION: The sonographic
features of primary papillary microcarcinoma of the thyroid are correlated with
high-volume central lymph node metastasis.
PMID- 29937169
TI - Association between robot-assisted surgery and resection quality in patients with
colorectal cancer.
AB - BACKGROUND: Resection quality after robot-assisted surgery for colorectal cancer
have not previously been investigated in a nationwide study. The aim of the study
was to examine the resection quality in robot-assisted versus laparoscopic
surgery for colorectal cancer. Furthermore, 30-day mortality, postoperative
complications, and conversion to open surgery were investigated. METHODS:
Patients undergoing either laparoscopic or robot-assisted surgery for colorectal
cancer between 1 January 2010 and 31 December 2015 were included. The primary
outcome was whether R0 resection was achieved. Secondary outcomes were 30-day
mortality, postoperative complications, and conversions to laparotomy. RESULTS: A
total of 8615 and 3934 patients had a diagnosis of colon cancer and rectal cancer
respectively. Of the patients with colon cancer, 511 patients underwent robot
assisted surgery and of the patients with rectal cancer, 706 patients underwent
robot-assisted surgery. In the multivariate analysis, patients with colon cancer
had an odds ratio (OR) = 0.63 (95%CI 0.45-0.88) for receiving R0 resection in the
robot-assisted group compared to laparoscopy. For patients with rectal cancer,
the OR was 1.20 (95%CI 0.89-1.61). No difference in 30-day mortality or
postoperative complications were observed. The OR of conversion to laparotomy was
lower in the robot-assisted group compared to the laparoscopic group in both
patients with colon - and rectal cancer. CONCLUSIONS: The study showed
significant lower odds of receiving R0 resection in patients with colon cancer
undergoing robot-assisted surgery. In patients with rectal cancer the robot
assisted surgery non-significantly increased the odds of receiving R0 resection.
PMID- 29937170
TI - Clinical significance of internal mammary lymph node metastasis for breast
cancer: Analysis of 337 breast cancer patients.
AB - PURPOSE: Internal mammary nodes (IMNs) is a major pathway of lymphatic drainage
for breast cancer, apart from axillary lymph node (ALN). However, owing to lack
of a feasible and safe biopsy method, management of IMNs is still controversial
in breast surgery. METHODS: From 2005 to 2009, a total of 337 consecutive breast
cancer women patients were recruited. All patients underwent IMNs biopsy through
intercostal space or endoscopic lymphatic chain resection. The ER, PR and HER-2
status were retested according to the current ASCO/CAP guidelines. We analyzed
the relationship between clinical pathological parameters and IMNs metastasis and
investigated the high risk factors and prognostic values of IMNs metastasis in
breast cancer. RESULTS: Among 337 patients, 314 patients underwent intercostal
space IMNs biopsy and 23 patients underwent endoscopic lymphatic chain resection.
A total of 63 (18.69%) patients were pathologically diagnosed with IMNs
metastasis. Among them, 28 (44.44%) patients changed the pathological lymph node
staging, and 15 cases (23.81%) changed the postoperative comprehensive treatment
program and accepted extended postoperative radiotherapy. Multivariate analysis
showed that compared with no ALN involvement, the risk of IMNs metastasis was
significantly increased in patients with 1-3 ALN involvement (OR = 42.097, 95% CI
= 5.225-339.178; P = 0.0004) and >=4 ALN involvement (OR = 82.429, 95%CI = 10.134
670.496; P < 0.0001). The risk of IMNs metastasis in HER-2 positive patients was
significantly higher than that in negative patients (OR = 5.452, 95% CI = 2.353
12.634; P < 0.0001). However, we did not find IMNs involvement was an independent
indicator for both overall survival and disease-free survival. CONCLUSIONS: Our
clinical practice and data indicated that IMNs biopsy through intercostal space
and endoscopic lymphatic chain resection are effective and minimally invasive
methods to detect the IMNs status, which may be helpful for accurate tumor
staging, risk assessment and option of chemotherapy or radiotherapy to improve
the patients' survival.
PMID- 29937171
TI - The effect of intravenous iron therapy on long-term survival in anaemic
colorectal cancer patients: Results from a matched cohort study.
AB - INTRODUCTION: Intravenous iron therapy has been shown to be advantageous in
treating anaemia and reducing the need for blood transfusions. Iron treatment,
however, may also be hazardous by supporting cancer growth. Present clinical
study explores, for the first time, the effect of preoperative intravenous iron
therapy on tumour prognosis in anaemic colorectal cancer patients. METHODS: A
retrospective cohort study was performed on consecutive patients who underwent
surgery for colorectal cancer between 2010 and 2016 in a single teaching
hospital. The primary outcomes were 5-year overall survival (OS) and disease-free
survival (DFS). Survival estimates were calculated using the Kaplan-Meier method
and patients were matched based on propensity score. RESULTS: 320 (41.0%) of all
eligible patients were anaemic, of whom 102 patients received preoperative
intravenous iron treatment (31.9%). After propensity score matching 83 patients
were included in both intravenous and non-intravenous iron group. The estimated 1
, 3-, and 5-year OS (91.6%, 73.1%, 64.3%, respectively) and DFS (94.5%, 86.7%,
83.4%, respectively) in the intravenous iron group were comparable with the non
intravenous iron group (p = 0.456 and p = 0.240, respectively). In comparing
patients with an event (death or recurrence) and no event in the intravenous iron
group, a distinct trend was found for decreased transferrin in the event group
(median 2.53 g/L vs 2.83 g/L, p = 0.052). CONCLUSION: The present study
illustrates that a dose of 1000-2000 mg preoperative intravenous iron therapy
does not have a profound effect on long-term overall and disease-free survival in
anaemic colorectal cancer patients. Future randomised trials with sufficient
power are required to draw definite conclusions on the safety of intravenous iron
therapy.
PMID- 29937172
TI - Low-cost, self-made CAD/CAM-guiding system for mandibular reconstruction.
AB - Facial symmetry, as well as function, remains the big challenge for surgeons who
attempt mandibular reconstruction. Nowadays several studies recommend the use of
computer aided surgery (CAS) and CAD/CAM technology to guide mandibular segmental
osteotomies and reconstruction using free fibula flap. Although these systems
have radically changed the way of doing mandibular reconstructive surgery, they
are expensive and require extended periods of time for prototypation. This may be
an important limitation in case of malignant neoplasms which require short-term
treatment. The aim of our study is to investigate the reliability and efficiency
of a protocol to obtain cutting guides produced in a "homemade" way. This study
includes four consecutive patients who underwent a segmental mandibulectomy and
fibula osteo-cutaneous free flap reconstruction for oral squamous cell carcinoma
between January and September 2016. The CAD/CAM system algorithm proposed was
based on the use of free open source software for digital planning and 3D layer
plastic deposition printer. A cost of about 3 Euro for each case was estimated.
An average mean distance between 3D preoperative and postoperative mesh points of
1.631 mm and a standard deviation of 5.496 mm has been demonstrated by 3D volume
overlay analysis. Overlapping results with much shorter prototyping time was
required with the in-house procedure described as compared to the available
commercial system. In conclusion, we expect that this technique will reduce
operative time and cost however further study and large series are needed to
confirm our results and better define the applicability in everyday surgical
practice.
PMID- 29937173
TI - Whole Blood Gene Expression Profiling in patients undergoing colon cancer surgery
identifies differential expression of genes involved in immune surveillance,
inflammation and carcinogenesis.
AB - INTRODUCTION: Cancer surgery may represent a potential risk of enhanced growth
and metastatic ability of residual cancer cells due to post-operative immune
dysfunction. This study identifies changes in transcription of genes involved in
immune surveillance, immune suppression and carcinogenesis in the post-operative
period of laparoscopic colon-cancer surgery within an ERAS regime. METHODS:
Patients undergoing elective, curatively intended laparoscopic surgery for colon
cancer stage I-III UICC were included in the study. Patients followed standard of
care in an ERAS setting. Whole blood gene expression profiling (WBGP) was
performed on the day prior to surgery and 1, 2, 3 and 10-14 days after surgery.
Samples were collected in Paxgene tubes and Labeled cDNA was fragmented and
hybridized to Affymetrix GeneChipTM 2.0. Results were corrected for multiple
hypothesis testing using the false discovery rate. Pathway analysis was performed
through the Molecular Signature Database. Paired fold changes of gene expression
were calculated for post-operative compared to pre-operative samples. A mixed
effect model was used to test differential gene expression by repeated-measures
ANOVA. RESULTS: WBGP of 33,804 genes at five timepoints in six patients showed
302 significantly differentially expressed genes between samples from the day
prior to surgery and the day after surgery. Pathway gene enrichment analysis
showed a downregulation of immunologically relevant pathways. There was a
significant downregulation of genes involved in T-cell receptor signaling,
antigen presentation and NK-cell activity after surgery. Furthermore, there was
an upregulation of cytokines related to metastatic ability, growth and
angiogenesis. CONCLUSION: Whole blood gene expression profiling revealed
dysregulation of genes involved in immune surveillance, inflammation and
carcinogenesis, after laparoscopic colon cancer surgery.
PMID- 29937174
TI - Oncologic outcomes of preoperative stent insertion first versus immediate surgery
for obstructing left-sided colorectal cancer.
AB - BACKGROUND: Colonic self-expanding metallic stenting (SEMS) is widely used for
the treatment of malignant colonic obstruction as a bridge to elective surgery.
However, the effects of colonic stenting on long-term oncologic outcomes are
debatable. This study aimed to compare the long-term oncologic outcomes of
preoperative SEMS insertion with those of immediate surgery in patients with
obstructing left-sided colorectal cancer. METHODS: A cohort of consecutive
patients who underwent radical surgery for obstructing left-sided colorectal
cancer between 2004 and 2011 in five tertiary referral hospitals were analyzed.
Long-term survivals were analyzed and adjusted using the inverse probability of
treatment weighting method, based on propensity scores, to reduce selection bias.
RESULTS: One hundred and nine patients underwent immediate surgery, and 226
underwent stent insertion before surgery. Disease-free survival did not differ
significantly in both the unadjusted population (hazard ratio [HR] 1.063, 95%
confidence interval [CI] 0.730-1.548; Log-rank, p = 0.746) and the adjusted
population (HR 0.122, 95% CI 0.920-1.987; Log-rank, p = 0.122). Overall survival
also did not differ significantly in both the unadjusted population (HR 0.871,
95% CI 0.568-1.334; Log-rank, p = 0.526) and the adjusted population (HR 1.023,
95% CI 0.665-1.572; Log-rank, p = 0.916). Defunctioning stoma formation was less
in the SEMS insertion group than immediate surgery group (adjusted, 14.6% vs.
41.3%, p < 0.001). CONCLUSION: The 'bridge to surgery' strategy using metallic
stents was oncologically comparable to immediate surgery in patients with
malignant left-sided colorectal obstruction.
PMID- 29937175
TI - Evaluation of optical imaging agents in a fluorescence-guided surgical model of
head and neck cancer.
AB - BACKGROUND: Tumor proliferation often occurs from pathologic receptor
upregulation. These receptors provide unique targets for near-infrared (NIR)
probes that have fluorescence-guided surgery (FGS) applications. We demonstrate
the use of three smart-targeted probes in a model of head and neck squamous cell
carcinoma. METHODS: A dose escalation study was performed using IntegriSense750,
ProSense750EX, and ProSense750FAST in mice (n = 5) bearing luciferase-positive
SCC-1 flank xenograft tumors. Whole body fluorescence imaging was performed
serially after intravenous injection using commercially available open-field
(LUNA, Novadaq, Canada) and closed-field NIR systems (Pearl, LI-COR, Lincoln,
NE). An ex vivo, whole-body biodistribution was conducted. Lastly, FGS was
performed with IntegriSense750 to demonstrate orthotopic and metastatic disease
localization. RESULTS: Disease fluorescence delineation was assessed by tumor-to
background fluorescence ratios (TBR). Peak TBR values were 3.3 for 1 nmol
ProSense750EX, 5.5 for 6 nmol ProSense750FAST, and 10.8 for 4 nmol
IntegriSense750 at 5.5, 3, and 4 d post administration, respectively. Agent
utility is unique: ProSense750FAST provides sufficient contrast quickly (TBR:
1.5, 3 h) while IntegriSense750 produces strong (TBR: 10.8) contrast with
extended administration-to-resection time (96 h). IntegriSense750 correctly
identified all diseased nodes in situ during exploratory surgeries. Ex vivo,
whole-body biodistribution was assessed by tumor-to-tissue fluorescence ratios
(TTR). Agents provided sufficient fluorescence contrast to discriminate disease
from background, TTR>1. IntegriSense750 was most robust in neural tissue (TTR:
64) while ProSense750EX was superior localizing disease against lung tissue (TBR:
13). CONCLUSION: All three agents appear effective for FGS.
PMID- 29937176
TI - Characterization of adrenocortical tumors by 18F-FDG PET/CT: Does steroid hormone
hypersecretion status modify the uptake pattern?
AB - BACKGROUND: adrenal tumor-to-liver uptake value (Tmx:Lmx) on 18F-FDG PET/CT is an
accurate and reproducible PET parameter in the distinction between benign and
malignant adrenal masses. The potential impact of steroid hormone secretion on
18F-FDG uptake is still debatable. The aim of this study was to evaluate this
relationship. METHODS: 2010-2015: 73 patients who underwent adrenalectomy for
adrenocortical tumors [49 secreting/(SA) and 24 non-secreting/(NSA)] were
retrospectively included in the study. Fourteen were malignant. All patients
underwent hormonal evaluation, functional and anatomical imaging, Weiss scoring
and Ki 67 evaluation. RESULTS: malignant tumors exhibit higher SUVmax than benign
tumors (median 7.75 vs 3.06 respectively, p < 0.001) and Tmx:Lmx was 2.7 vs 1.17
for benign tumors, p < 0.001. Tmx:Lmx was positively correlated to Weiss score (p
< 0.001). No significant difference was observed for Tmx:Lmx between SA and NSA
overall (p = 0.851), regardless of the subgroup of tumors analyzed. Tmx:Lmx was
not correlated to tumor size (p < 0.508) or 24 h free urinary cortisol level (p <
0.522). CONCLUSIONS: no correlation was observed between Tmx:Lmx and hormonal
status, however the correlation between ratio, malignancy and Weiss score confirm
the utility of 18F-FDG PET/CT for the differentiation of benign from malignant
adrenal lesions, irrespective of the hormone secretory status of the tumor. 18F
FDG PET/CT is a useful biomarker in the diagnosis of adrenal tumors, regardless
of the secretion status.
PMID- 29937177
TI - NACT and laparoscopic-assisted radical vaginal trachelectomy in young patients
with large (2-5 cm) high risk cervical cancers: Safety and obstetrical outcome.
PMID- 29937178
TI - Do patients with pancreatic body or tail cancer benefit from adjuvant therapy?A
cohort study.
AB - INTRODUCTION: Evidence supporting adjuvant therapy for resected pancreatic cancer
is limited primarily to head tumors. We analyzed data from the National Cancer
Database (NCDB) to evaluate the relationship of tumor site with benefit from
adjunctive (adjuvant, neoadjuvant, perioperative) therapy (Rx). METHODS: All NCDB
patients with clinical stage I and II pancreatic cancer, diagnosed from 2003 to
2013, who underwent surgical resection and had data on site of primary were
included. Overall survival (OS) analyses with hazard ratios (HR), 95% confidence
intervals (CI), and two-sided p-values are presented. RESULTS: A total of 27,930
patients met inclusion criteria; median age 66 years, 51% males, 86% white.
Primary site was coded as head (74.4%), body (9.3%), or tail (16.3%). Pathologic
stage was predominantly stage II (77%); 81% had negative margins. Perioperative
Rx was used in 4%, neoadjuvant in 8%, adjuvant in 48%. Median OS for the cohort
was 24 months; for head, body and tail tumors, it was 21.6, 34.5, and 42.5
months, respectively. In univariable analyses, adjunctive Rx was associated with
improved OS in head tumors (HR, any Rx vs. no Rx: 0.87; 95% CI 0.84-0.91; p <
0.0001) but not in body (1.82; 1.59-2.08; <0.0001) and tail (2.28; 2.05-2.53;
<0.0001) tumors; multivariable models including statistically significant
predictors (Charlson-Deyo comorbidity score, tumor grade and stage, positive
resection margin) confirmed these results. CONCLUSIONS: Our study suggests that
the benefit of adjunctive Rx is restricted to pancreatic head tumors; body and
tail tumors have a much better prognosis. These results warrant further
evaluation in prospective studies.
PMID- 29937179
TI - HIPEC in patients with primary advanced ovarian cancer: Is there a role? A
systematic review of short- and long-term outcomes.
AB - A systematic review of the studies where HIPEC combined with cytoreductive
surgery was used in patients with primary advanced ovarian cancer was performed
to understand is there a role for this treatment modality not only in recurrent
but in primary advanced ovarian cancer. The results are controversial but there
is a strong trend for improvement of the long-term outcomes of patients with
primary advanced ovarian cancer after HIPEC.
PMID- 29937180
TI - Significance of PD-L1 expression in pulmonary metastases from head and neck
squamous cell carcinoma.
AB - BACKGROUND: The mechanism by which tumors escape the immune system has been
actively investigated and is partly explained by the programmed death-1 (PD-1)
and its ligand (PD-L1) pathway. This study is aimed at clarifying the prognostic
significance of PD-L1 expression in patients with surgically resected pulmonary
metastases of head and neck squamous cell carcinoma (HNSCC). PATIENTS AND
METHODS: A retrospective review was conducted of 26 HNSCC patients who underwent
complete resection of pulmonary metastases. PD-L1 expression in both the primary
and metastatic tumors was evaluated using immunohistochemistry (anti-PD-L1
antibody, clone SP263). High PD-L1 expression was defined as >=50% of tumor cells
with positive staining. Survival and prognostic impacts following pulmonary
metastasectomy were analyzed based on the PD-L1 expression level. RESULTS: The
patients included 23 men and 3 women, with a median age of 65 years. Six (23%) of
the pulmonary metastatic cases showed high PD-L1 expression, while their
corresponding primary lesions had low PD-L1 expression. The 5-year overall
survival rate after pulmonary metastasectomy was 57.6% in all cases. The 5-year
overall survival rates were 72.5% and 16.7% in the low and high PD-L1 groups,
respectively (p < 0.001). Multivariate analysis demonstrated that high PD-L1
expression and older age (>65 years) correlated independently with a shorter
overall survival (p < 0.001). CONCLUSIONS: High PD-L1 expression in pulmonary
metastases could be an independent predictor of poor outcome in HNSCC patients
undergoing pulmonary metastasectomy. This is the first report evaluating the
prognostic implication of PD-L1 expression in metastatic HNSCC.
PMID- 29937181
TI - Effects of anesthetic interventions on breast cancer behavior, cancer-related
patient outcomes, and postoperative recovery.
AB - This narrative review will summarize our current understanding of the effects of
perioperative interventions on patients undergoing surgical removal of breast
malignancies. It will focus on how different anesthetic agents and perioperative
interventions might affect both breast cancer behavior and/or tumor recurrence as
well as postoperative recovery. The main objective of this study will be to
describe the evidence and critically analyze preclinical and clinical studies on
the use of intravenous versus inhaled anesthetic agents, opioids, regional
anesthetics, and anesthetic adjuncts in patients undergoing breast cancer
resection. We will look both at the evidence regarding cancer-related outcomes
and postoperative recovery. A search of PubMed, from inception to May 2017 was
performed using Mesh terms Breast Neoplasms [Mesh] OR cancer AND breast AND
Anesthesia [Mesh]; "Anesthetics"[Mesh] AND "Breast Neoplasms/surgery"[Mesh].
Although no optimal anesthetic combination has been identified for patients
undergoing breast cancer resection, it should be noted that based on the
available evidence, an ideal anesthetic in this patient population would involve
a combination of TIVA (propofol), regional anesthesia (paravertebral block)), non
opioid sedatives (clonidine or dexmedetomidine), and COX-2 inhibition
(ketorolac). Based on the current evidence, this combination of anesthetic and
analgesic agents has the best chance of improving cancer-related outcomes and
postoperative recovery.
PMID- 29937182
TI - Rationale for the administration of systemic 5-FU in combination with heated
intraperitonal oxaliplatin.
AB - BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
(HIPEC) with oxaliplatin (OX) is the standard of care for selected patients with
peritoneal carcinomatosis of colorectal origin. Because 5-FU is mandatory to
improve efficacy of OX when used by systemic route, several teams now empirically
combine intravenous (IV) 5-FU with HIPEC OX, but this practice has yet to be
supported by preclinical data. Using a murine model, we studied the impact of IV
5-FU on peritoneal absorption of HIPEC OX. METHODS: Under general anesthesia, 24
Sprague-Dawley rats were submitted to 4 different doses of IV 5-FU (0, 100, 400
and 800 mg/m2) and a fixed dose of HIPEC OX (460 mg/m2) perfused at 40 degrees C
during 25 min. At 25 min, samples in different compartments were harvested
(peritoneum, portal vein and systemic blood) and the concentrations of 5-FU and
OX were measured by high performance liquid chromatography. RESULTS: Peritoneal
absorption of OX was significantly higher (17.0, 20.1, 34.9 and 38.1 nmol/g, p <
0.0001) with increasing doses of 5-FU (0, 100, 400 and 800 mg/m2, respectively).
Peritoneal absorption of OX reached a plateau between 400 and 800 mg/m2 of IV 5
FU. CONCLUSION: IV 5-FU enhances peritoneal absorption of HIPEC OX. The most
efficient dose of IV 5-FU to be used in combination with HIPEC OX seems to be 400
mg/m2.
PMID- 29937183
TI - Clinical significance and prognostic relevance of KRAS, BRAF, PI3K and TP53
genetic mutation analysis for resectable and unresectable colorectal liver
metastases: A systematic review of the current evidence.
AB - BACKGROUND: Hepatic resection is considered the optimal potentially curative
treatment for colorectal liver metastases (CRLM). Following resection, up to two
thirds of patients will develop recurrence within 5-years. Genetic mutation
analysis of CRLM, especially KRAS status, has been proposed as a means to guide
treatment, as well as identifying patients who can derive the most survival
benefit from hepatic resection. METHODS: A systematic review of the literature
was conducted the PubMed, Embase and Cochrane library through February 8th, 2018.
The following algorithm was applied: "(colorectal OR rectal OR colon OR colonic)
AND (liver OR hepatic) AND (metastasis OR metastases) AND (gene OR mutation OR
KRAS OR BRAF OR SMAD4 OR RAS OR TP53 OR P53 OR APC OR PI3K OR MSI OR EGFR OR
MACC1 OR microsatellite)." RESULTS: From the 2404 records retrieved, 78 studies
were finally deemed eligible; 47 studies reported mutational data on patients
with resectable CRLM, whereas 31 studies reported on patients with unresectable
CRLM. Mutational analyses were mostly performed on the CRLM specimen rather than
the primary CRC. The vast majority of studies reported on the KRAS mutational
status (88.5%, n = 69/78). Prevalence of KRAS mutations ranged from 25% to 52%.
Most studies reported that RAS mutation was a negative prognostic factor for
overall (OS) (n = 24) and recurrence-free (RFS) (n = 9) survival; a few reports
noted no effect of RAS mutational status on OS (n = 4) or RFS (n = 6). Twelve
studies reported on BRAF mutations with a prevalence of BRAF mutation ranging
from 0 to 9.1% in resected CRLM specimens. BRAF mutation was strongly associated
with a worse prognosis. TP53 and PIK3CA gene mutations did not affect long-term
outcomes. CONCLUSIONS: The biological status of each tumor provides the basis for
individualized cancer therapeutics. Data on the mutational status on CRLM should
be a part of multidisciplinary discussions to help inform the therapeutic
approach, type of chemotherapy, as well as timing and approach of surgical
resection.
PMID- 29937184
TI - Prehabilitation for radical prostatectomy: A multicentre randomized controlled
trial.
AB - INTRODUCTION: Preoperative exercise and fitness are predictors of surgical
recovery; however, little is known of the effect of preoperative exercise-based
conditioning, known as prehabilitation, in this for men undergoing radical
prostatectomy. Our study examined the feasibility and effects of prehabilitation
on perioperative and postoperative outcomes in men undergoing radical
prostatectomy. METHODS: This feasibility RCT compared prehabilitation (PREHAB)
versus a control condition (CON) in 86 men undergoing radical prostatectomy.
PREHAB consisted of home-based, moderate-intensity exercise prior to surgery.
Both groups received a preoperative pelvic floor training regimen. Feasibility
was assessed via rates of recruitment, attrition, intervention duration and
adherence, and adverse events. Clinical outcomes included surgical complications,
and length of stay. The following outcomes were assessed at baseline, prior to
surgery, and 4, 12, and 26-weeks postoperatively: 6-min walk test (6MWT), upper
extremity strength, quality of life, psychosocial wellbeing, urologic symptoms,
and physical activity volume. RESULTS: The recruitment rate was 47% and attrition
rates were 25% and 33% for PREHAB and CON, respectively. Adherence to PREHAB was
69% with no serious intervention-related adverse events. After the intervention
and prior to surgery, PREHAB participants demonstrated less anxiety (P = 0.035)
and decreased body fat percentage (P = 0.001) compared to CON. Four-weeks
postoperatively, PREHAB participants had greater 6MWT scores of clinical
significance compared to CON (P = 0.006). Finally, compared to CON, grip strength
and anxiety were also greater in the PREHAB at 26-weeks (P = 0.022) and (P =
0.025), respectively. CONCLUSION: While feasible and safe, prehabilitation has
promising benefits to physical and psychological wellbeing at salient timepoints
relative to radical prostatectomy.
PMID- 29937185
TI - Prognostic impact of extranodal extension in stage 1B gastric carcinomas.
AB - BACKGROUND: In addition to the TNM stage, an additional prognostic factor is
needed to assess the prognosis of gastric cancer. Moreover, there is no consensus
on high-risk group of recurrence and adjuvant strategy in stage 1B gastric
cancers. We aimed to investigate the prognostic significance of extranodal
extension (ENE) in stage 1B gastric carcinomas and assess whether ENE can
indicate the need for adjuvant treatment. METHODS: The clinicopathological
characteristics of 1588 patients who underwent curative gastrectomy with more
than D1 plus lymphadenectomy for stage 1B gastric cancer from 2003 to 2010 were
reviewed. A propensity score matching analysis was performed. RESULTS: Age over
65 years and the presence of ENE were found to be poor prognostic factors for
both overall survival (OS) and disease-free survival (DFS). Adjuvant chemotherapy
was related to an increased overall survival. The 5 year OS and DFS rates were
88.7% and 86.2%, respectively. When divided into 3 groups (early gastric cancer
with ENE [T1N1 ENE(+)], early cancer without ENE [T1N1 ENE(-)], and advanced
tumor without nodal metastasis [T2N0]), the OS and DFS rates of the T1N1 ENE(+)
group were significantly worse than those of the other groups (5 year OS rate of
72.7% vs. 88.4% vs. 91.9%, respectively, P < 0.001 and 5 year DFS rate of 67.2%
vs. 85.2% vs. 91.5%, respectively, P < 0.001). CONCLUSION: ENE is an independent
prognostic factor that predicted poor outcomes for stage 1B gastric cancers and
it could be an indicator of the need for adjuvant treatment.
PMID- 29937186
TI - Up-regulated BCAR4 contributes to proliferation and migration of cervical cancer
cells.
AB - OBJECTIVES: Recently, thousands of long non-coding RNAs (lncRNAs) involved in
development and metastasis of malignant tumors have been identified. Long non
coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) has been
proved to promote proliferation and metastasis in multiple tumors. However, the
function and significance of BCAR4 in cervical cancer are still unclear. METHODS:
In this study, we concentrated on the biological function and clinical
significance of BCAR4 in cervical cancer. More specifically, BCAR4 expression was
evaluated in cervical cancer tissues and cell lines by qRT-PCR. Moreover, the
prognostic factors were assessed by Kaplan-Meier analysis and Cox proportional
hazards models. Additionally, functional assays were conducted and the potential
mechanism was explored. RESULTS: Our study showed that BCAR4 expression was
significantly up-regulated in cervical cancer tissue and cell lines. Moreover,
patients with high BCAR4 expression showed worse survival outcomes and
overexpression of BCAR4 might be an independent prognostic factor in cervical
cancer. Furthermore, overexpression of BCAR4 remarkably promoted the
proliferation, motility of cervical cancer cells and silencing BCAR4
significantly suppressed the proliferation, migration and invasion of cervical
cancer cells. Additionally, overexpression of BCAR4 promoted epithelial
mesenchymal transition (EMT) process and silencing BCAR4 suppressed EMT process
in cervical cancer cells. CONCLUSIONS: The results indicated that BCAR4 might
play a crucial role in cervical cancer progression and act as an underlying
biomarker for the diagnosis and prognosis of cervical cancer.
PMID- 29937187
TI - High snail expression predicts a poor prognosis in breast invasive ductal
carcinoma patients with HER2/EGFR-positive subtypes.
AB - BACKGROUND: High Snail expression is known as a poor prognostic factor in breast
cancer. However, its prognostic impact for breast cancer with different molecular
subtypes is still controversial. METHODS: Snail expression was examined by
immunohistochemistry in tissue microarray slides of 85 corresponding tumor
adjacent normal (CTAN) and 247 breast invasive ductal carcinoma (IDC) tissues.
Multivariable Cox regression analysis was used to assess the impact of Snail
expression on survival rate by different molecular subtypes of breast IDC
patients. RESULTS: The level of Snail expression in IDC tumor tissues was
significantly higher than that in CTAN tissues. Moreover, high Snail expression
had direct impacts on poor disease specific survival (DSS) and disease-free
survival (DFS) in breast IDC patients with human epidermal growth factor receptor
2 (HER2)-positive and human epidermal growth factor receptor (EGFR)-positive
statuses as well as the HER2 intrinsic subtype. Additionally, breast IDC patients
with a combination of three prognostic factors, including high Snail expression
and HER2-positive and EGFR-positive statuses, had much poor DSS and DFS with a
statistically significant linear trend. CONCLUSION: High Snail expression could
predict a poor prognosis for breast IDC patients with HER2/EGFR-positive
subtypes.
PMID- 29937188
TI - Spinal metastases in multiple myeloma: A high-risk subgroup for ISS III patients.
AB - BACKGROUND: Patients with multiple myeloma (MM) have an extremely heterogeneous
prognosis. The International Staging System (ISS) is actually the most reliable
staging system and chromosomal abnormalities were integrated in the Revised-ISS.
We wanted to evaluate the prognostic value of spinal secondary localization in
patients with MM and its impact on the ISS. METHODS: Epidemiological and
biological data, as well as treatment protocols and secondary localization were
analyzed for 650 consecutive patients diagnosed with MM from January 2006 to
January 2017. RESULTS: The overall survival (OS) was dependent on the WHO
performance status, ISS and Salmon and Durie stage at diagnosis. Furthermore,
presence of spinal metastases at diagnosis was predictive of a worse outcome (p <
0.0001), while presence of peripheral bone metastases was not. Spinal metastases
had a significant impact on OS for ISS III patients (p < 0.0001). Also, a history
of bone marrow graft was associated with a better OS (p < 0.0001), while
radiotherapy had no significant impact. The multivariate analysis confirmed that
the spinal metastases at diagnosis determined a high-risk subgroup for ISS III
patients with a very poor OS (p < 0.0001). CONCLUSIONS: Spinal metastases are a
negative prognostic factor for patients with MM, especially for ISS III patients,
and are associated with a shorter OS. Spinal metastasis should be systemically
searched for and should be included in a modified staging system to better manage
these patients.
PMID- 29937189
TI - Rectal Cancer Management- no longer a solo sport for surgeons.
PMID- 29937190
TI - Operative Approach to Rectal Cancer: An Anatomical and Technical Description.
PMID- 29937191
TI - Police violence and the built harm of structural racism.
PMID- 29937192
TI - Sepsis and septic shock.
AB - Sepsis is a common condition that is associated with unacceptably high mortality
and, for many of those who survive, long-term morbidity. Increased awareness of
the condition resulting from ongoing campaigns and the evidence arising from
research in the past 10 years have increased understanding of this problem among
clinicians and lay people, and have led to improved outcomes. The World Health
Assembly and WHO made sepsis a global health priority in 2017 and have adopted a
resolution to improve the prevention, diagnosis, and management of sepsis. In
2016, a new definition of sepsis (Sepsis-3) was developed. Sepsis is now defined
as infection with organ dysfunction. This definition codifies organ dysfunction
using the Sequential Organ Failure Assessment score. Ongoing research aims to
improve definition of patient populations to allow for individualised management
strategies matched to a patient's molecular and biochemical profile. The search
continues for improved diagnostic techniques that can facilitate this aim, and
for a pharmacological agent that can improve outcomes by modifying the disease
process. While waiting for this goal to be achieved, improved basic care driven
by education and quality-improvement programmes offers the best hope of
increasing favourable outcomes.
PMID- 29937193
TI - Police killings and their spillover effects on the mental health of black
Americans: a population-based, quasi-experimental study.
AB - BACKGROUND: Police kill more than 300 black Americans-at least a quarter of them
unarmed-each year in the USA. These events might have spillover effects on the
mental health of people not directly affected. METHODS: In this population-based,
quasi-experimental study, we combined novel data on police killings with
individual-level data from the nationally representative 2013-15 US Behavioral
Risk Factor Surveillance System (BRFSS) to estimate the causal impact of police
killings of unarmed black Americans on self-reported mental health of other black
American adults in the US general population. The primary exposure was the number
of police killings of unarmed black Americans occurring in the 3 months prior to
the BRFSS interview within the same state. The primary outcome was the number of
days in the previous month in which the respondent's mental health was reported
as "not good". We estimated difference-in-differences regression models-adjusting
for state-month, month-year, and interview-day fixed effects, as well as age,
sex, and educational attainment. We additionally assessed the timing of effects,
the specificity of the effects to black Americans, and the robustness of our
findings. FINDINGS: 38 993 (weighted sample share 49%) of 103 710 black American
respondents were exposed to one or more police killings of unarmed black
Americans in their state of residence in the 3 months prior to the survey. Each
additional police killing of an unarmed black American was associated with 0.14
additional poor mental health days (95% CI 0.07-0.22; p=0.00047) among black
American respondents. The largest effects on mental health occurred in the 1-2
months after exposure, with no significant effects estimated for respondents
interviewed before police killings (falsification test). Mental health impacts
were not observed among white respondents and resulted only from police killings
of unarmed black Americans (not unarmed white Americans or armed black
Americans). INTERPRETATION: Police killings of unarmed black Americans have
adverse effects on mental health among black American adults in the general
population. Programmes should be implemented to decrease the frequency of police
killings and to mitigate adverse mental health effects within communities when
such killings do occur. FUNDING: Robert Wood Johnson Foundation and National
Institutes of Health.
PMID- 29937194
TI - Personalised recovery after general and gynaecologic surgery.
PMID- 29937196
TI - Struggle with Pharmacotherapy for Underactive Bladder: Could Patients with
Detrusor Underactivity Benefit from Transient Receptor Potential Vanilloid 4
Agonists?
PMID- 29937195
TI - Personalised perioperative care by e-health after intermediate-grade abdominal
surgery: a multicentre, single-blind, randomised, placebo-controlled trial.
AB - BACKGROUND: Instructing and guiding patients after surgery is essential for
successful recovery. However, the time that health-care professionals can spend
with their patients postoperatively has been reduced because of efficiency
driven, shortened hospital stays. We evaluated the effect of a personalised e
health-care programme on return to normal activities after surgery. METHODS: A
multicentre, single-blind, randomised controlled trial was done at seven teaching
hospitals in the Netherlands. Patients aged 18-75 years who were scheduled for
laparoscopic cholecystectomy, inguinal hernia surgery, or laparoscopic adnexal
surgery for a benign indication were recruited. An independent researcher
randomly allocated participants to either the intervention or control group using
computer-based randomisation lists, with stratification by sex, type of surgery,
and hospital. Participants in the intervention group had access to a
perioperative, personalised, e-health-care programme, which managed recovery
expectations and provided postoperative guidance tailored to the patient. The
control group received usual care and access to a placebo website containing
standard general recovery advice. Participants were unaware of the study
hypothesis and were asked to complete questionnaires at five timepoints during
the 6-month period after surgery. The primary outcome was time between surgery
and return to normal activities, measured using personalised patient-reported
outcome measures. Intention-to-treat and per-protocol analyses were done. This
trial is registered in the Netherlands National Trial Register, number NTR4699.
FINDINGS: Between Aug 24, 2015, and Aug 12, 2016, 344 participants were enrolled
and randomly allocated to either the intervention (n=173) or control (n=171)
group. 14 participants (4%) were lost to follow-up, with 330 participants
included in the primary outcome analysis. Median time until return to normal
activities was 21 days (95% CI 17-25) in the intervention group and 26 days (20
32) in the control group (hazard ratio 1.38, 95% CI 1.09-1.73; p=0.007).
Complications did not differ between groups. INTERPRETATION: A personalised e
health intervention after abdominal surgery speeds up the return to normal
activities compared with usual care. Implementation of this e-health programme is
recommended in patients undergoing intermediate-grade abdominal, gynaecological,
or general surgical procedures. FUNDING: ZonMw.
PMID- 29937197
TI - "Don't Let the Perfect Be the Enemy of the Good": Time to Embrace Magnetic
Resonance Imaging Before First Prostate Biopsy.
PMID- 29937198
TI - Active Surveillance for Low-risk Prostate Cancer: The European Association of
Urology Position in 2018.
AB - : Active surveillance (AS) represents a well-recognized management option for
many patients with low- and very low-risk prostate cancer (PCa). AS aims to
reduce overtreatment whilst ensuring curative treatment for those in whom it is
needed, without losing the window of curability. While long-term series have
confirmed the safety of AS in carefully selected patients, this has resulted in
new clinical questions. Can the inclusion criteria be expanded? Is there a role
for biomarkers and multiparametric magnetic resonance imaging at diagnosis or
during AS? What is the optimal follow-up schedule as well as the most meaningful
trigger for definitive treatment? These questions, together with increasingly
adopted heterogeneous protocols in AS, have prompted the European Association of
Urology to produce a position paper corroborated by a summary of the scientific
background on AS. PATIENT SUMMARY: Active surveillance (AS) is becoming a widely
adopted strategy for patients affected by low-risk prostate cancer. While a
formal systematic review on the topic will soon be available, the European
Association of Urology has produced specific statements for different open
questions on AS.
PMID- 29937199
TI - Distinct habitat use strategies of sympatric rorqual whales within a fjord
system.
AB - We used ecosystem sampling during systematic surveys and opportunistic focal
follows, comparison tests, and random forest models to evaluate fin whale
(Balaenoptera physalus) and humpback whale (Megaptera novaeangliae) habitat
associations within an inland feeding ground (Kitimat Fjord System, British
Columbia, Canada). Though these species are sympatric and share a common prey
source, they were attuned to different aspects of the local habitat. The fin
whales were associated with habitat properties reminiscent of the open ocean.
Humpback whales, in contrast, were associated with features more commonly
associated with the inland waters of fjords. Fixed habitat features, such as
seafloor depth and distance from the fjord mouth, were the most important
predictors of fin whale presence, but fixed and dynamic variables, such as
surface properties, predicted humpback whale presence with equal (moderate)
success. With the exception of strong salinity gradients for humpback whales,
habitat conditions were poor predictors of feeding state. Fin whales practiced a
spatially confined, seasonally stable, and thus more predictable use of certain
channels within the fjord system. These findings are compatible with site loyal
behavior, which is interesting in light of the species' historical, unique use of
this fjord system. The relatively lackluster performance of humpback-habitat
models, coupled with the importance of oceanographic properties, makes the
humpback's habitat use strategy more uncertain. The fact that two sympatric
species sharing a common prey source exhibited different habitat use strategies
suggests that at least one species was informed by something in addition to prey.
Given that the two species are attuned to different aspects of the fjord habitat,
their responses to habitat changes, including anthropogenic impacts, would likely
be different in both nature and degree. Our findings highlight the value of
comparative studies and the complexity of rorqual habitat use, which must be
understood in order for critical habitat to be identified and protected.
PMID- 29937201
TI - Too Much Carrot and Not Enough Stick in New Stem Cell Oversight Trends.
AB - Regulators are now more often distinguishing between perceived good citizens and
"bad actors" in stem cell and regenerative medicine clinical research, resulting
in relatively more polar, carrot-and-stick oversight approaches. Here, I discuss
why there may be too much carrot and not enough stick by regulators for effective
enforcement.
PMID- 29937200
TI - Chronic Liver Injury Induces Conversion of Biliary Epithelial Cells into
Hepatocytes.
AB - Chronic liver injury can cause cirrhosis and impaired liver regeneration,
impairing organ function. Adult livers can regenerate in response to parenchymal
insults, and multiple cellular sources have been reported to contribute to this
response. In this study, we modeled human chronic liver injuries, in which such
responses are blunted, without genetic manipulations, and assessed potential
contributions of non-parenchymal cells (NPCs) to hepatocyte regeneration. We show
that NPC-derived hepatocytes replenish a large fraction of the liver parenchyma
following severe injuries induced by long-term thioacetamide (TAA) or 3,5
diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment. Through lineage tracing of
biliary epithelial cells (BECs), we show that BECs are a source of new
hepatocytes and gain an Hnf4alpha+CK19+ bi-phenotypic state in periportal regions
and fibrotic septa. Bi-phenotypic cells were also detected in cirrhotic human
livers. Together, these data provide further support for hepatocyte regeneration
from BECs without genetic interventions and show their cellular plasticity during
severe liver injury.
PMID- 29937202
TI - Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical
Reprogramming.
AB - Chemical reprogramming provides a powerful platform for exploring the molecular
dynamics that lead to pluripotency. Although previous studies have uncovered an
intermediate extraembryonic endoderm (XEN)-like state during this process, the
molecular underpinnings of pluripotency acquisition remain largely undefined.
Here, we profile 36,199 single-cell transcriptomes at multiple time points
throughout a highly efficient chemical reprogramming system using RNA-sequencing
and reconstruct their progression trajectories. Through identifying sequential
molecular events, we reveal that the dynamic early embryonic-like programs are
key aspects of successful reprogramming from XEN-like state to pluripotency,
including the concomitant transcriptomic signatures of two-cell (2C) embryonic
like and early pluripotency programs and the epigenetic signature of notable
genome-wide DNA demethylation. Moreover, via enhancing the 2C-like program by
fine-tuning chemical treatment, the reprogramming process is remarkably
accelerated. Collectively, our findings offer a high-resolution dissection of
cell fate dynamics during chemical reprogramming and shed light on mechanistic
insights into the nature of induced pluripotency.
PMID- 29937203
TI - hPSC Modeling Reveals that Fate Selection of Cortical Deep Projection Neurons
Occurs in the Subplate.
AB - Cortical deep projection neurons (DPNs) are implicated in neurodevelopmental
disorders. Although recent findings emphasize post-mitotic programs in projection
neuron fate selection, the establishment of primate DPN identity during layer
formation is not well understood. The subplate lies underneath the developing
cortex and is a post-mitotic compartment that is transiently and
disproportionately enlarged in primates in the second trimester. The evolutionary
significance of subplate expansion, the molecular identity of its neurons, and
its contribution to primate corticogenesis remain open questions. By modeling
subplate formation with human pluripotent stem cells (hPSCs), we show that all
classes of cortical DPNs can be specified from subplate neurons (SPNs). Post
mitotic WNT signaling regulates DPN class selection, and DPNs in the caudal fetal
cortex appear to exclusively derive from SPNs. Our findings indicate that SPNs
have evolved in primates as an important source of DPNs that contribute to
cortical lamination prior to their known role in circuit formation.
PMID- 29937204
TI - Guillain-Barre syndrome in pregnancy: Successful multidisciplinary approach.
PMID- 29937205
TI - Variational Algorithms for Analyzing Noisy Multistate Diffusion Trajectories.
AB - Single-particle tracking offers a noninvasive high-resolution probe of
biomolecular reactions inside living cells. However, efficient data analysis
methods that correctly account for various noise sources are needed to realize
the full quantitative potential of the method. We report algorithms for hidden
Markov-based analysis of single-particle tracking data, which incorporate most
sources of experimental noise, including heterogeneous localization errors and
missing positions. Compared to previous implementations, the algorithms offer
significant speedups, support for a wider range of inference methods, and a
simple user interface. This will enable more advanced and exploratory
quantitative analysis of single-particle tracking data.
PMID- 29937206
TI - A risk-based approach to development of ultrasound-based high-dose-rate prostate
brachytherapy quality management.
AB - PURPOSE: The purpose of this study was to apply a risk-based approach to the
development of a quality management (QM) program for ultrasound-based high-dose
rate (HDR) prostate brachytherapy (pBT) treatment planning and delivery. METHODS
AND MATERIALS: A QM program was developed by a multidisciplinary team, using both
an in-house risk-and-benefit balance impact template (RABBIT) tool and a failure
modes and effect analysis (FMEA). FMEA scores were determined by three
physicists, one radiation therapist and two radiation oncologists who were
familiar with the protocol. The QM program produced by both risk-based techniques
was then compared and consolidated. RESULTS: The RABBIT tool identified 26
potential risks during the treatment planning and delivery process. During the
FMEA, a total of 35 potential failure modes were identified from the seven major
processes in ultrasound-based HDR pBT. For the 35 potential failure modes, risk
priority number scores ranged from 14 to 267. The highest ranked failure mode was
identified to be mislabeling/connection of the transfer tubes/catheters. From the
risks analyses, a comprehensive QM program was developed. CONCLUSION: Both the
RABBIT tool and process mapping and FMEA were shown to be valuable tools in
developing a QM program for ultrasound-based HDR pBT treatments. A considerable
number of the potential failure modes identified in both tools were related to
human or procedural errors, highlighting the importance of checklists and
protocols in delivering a safe and effective ultrasound-based HDR pBT treatment.
PMID- 29937208
TI - Introduction to the special issue on quality of single-case experimental research
in developmental disabilities.
PMID- 29937207
TI - Multimodality imaging guidance for percutaneous paravalvular leak closure:
Insights from the multi-centre FFPP register.
AB - BACKGROUND: Percutaneous paravalvular leak (PVL) closure has emerged as a
palliative alternative to surgical management in selected high-risk patients.
Percutaneous procedures are challenging, especially for mitral PVL. Accurate
imaging of the morphologies of the defects is mandatory, together with precise
guidance in the catheterization laboratory to enhance success rates. AIMS: To
describe imaging modalities used in clinical practice to guide percutaneous PVL
closure and assess the potential of new imaging tools. METHODS: Data from the
'Fermeture de Fuite paraprothetique' (FFPP) register were used. The FFPP register
is an international multi-institutional collaborative register started in 2017
with a retrospective and a prospective part. A descriptive analysis of
multimodality imaging used to guide PVL closure in clinical practice was
performed. RESULTS: Data from 173 procedures performed in 19 centres from three
countries (France, Belgium and Poland) were collected, which included eight cases
of PVL following transcatheter valve replacement. Transoesophageal
echocardiography was used in 167 cases (96.5%) and 3D echocardiography in 87.4%
of cases. In one case, 3D-echocardiography was fused with fluoroscopy images in
real time using echonavigator software. Details about multimodality imaging were
available from a sample of 31 patients. Cardiac computed tomography (CT) was
performed before 10 of the procedures. In one case, fusion between preprocedural
cardiac CT angiography data and fluoroscopy data was used. In two cases, a 3D
model of the valve with PVL was printed. CONCLUSION: Echocardiography,
particularly the 3D mode, is the cornerstone of PVL imaging. Other imaging
modalities, such as cardiac CT and cardiac magnetic resonance imaging, may be of
complementary interest. New techniques such as imaging fusion and printing may
further facilitate the percutaneous approach of PVLs.
PMID- 29937209
TI - Proton therapy for pediatric malignancies: Fact, figures and costs. A joint
consensus statement from the pediatric subcommittee of PTCOG, PROS and EPTN.
AB - Radiotherapy plays an important role in the management of childhood cancer, with
the primary aim of achieving the highest likelihood of cure with the lowest risk
of radiation-induced morbidity. Proton therapy (PT) provides an undisputable
advantage by reducing the radiation 'bath' dose delivered to non-target
structures/volume while optimally covering the tumor with tumoricidal dose. This
treatment modality comes, however, with an additional costs compared to
conventional radiotherapy that could put substantial financial pressure to the
health care systems with societal implications. In this review we assess the data
available to the oncology community of PT delivered to children with cancer,
discuss on the urgency to develop high-quality data. Additionally, we look at the
advantage of combining systemic agents with protons and look at the cost
effectiveness data published so far.
PMID- 29937210
TI - Harnessing drug/radiation interaction through daily routine practice: Leverage
medical and methodological point of view (MORSE 02-17 study).
AB - BACKGROUND: Safety profile of the interaction between anticancer drugs and
radiation is a recurrent question. However, there are little data regarding the
non-anticancer treatment (NACT)/radiation combinations. The aim of the present
study was to investigate concomitant NACTs in patients undergoing radiotherapy in
a French comprehensive cancer center. METHODS: A prospective cross-sectional
study was conducted. All cancer patients undergoing a palliative or curative
radiotherapy were consecutively screened for six weeks in 2016. Data on NACTs
were collected. RESULTS: Out of 214 included patients, a NACT was concomitantly
prescribed to 155 patients (72%), with a median number of 5 NACTs per patient
(range: 1-12). The most prescribed drugs were anti-hypertensive drugs (101
patients, 47.2%), psychotropic drugs (n = 74, 34.6%), analgesics (n = 78, 36.4%),
hypolipidemic drugs (n = 57, 26.6%), proton pump inhibitors (n = 46, 21.5%) and
antiplatelet drugs (n = 38, 17.8%). Although 833 different molecules were
reported, only 20 possible modifiers of cancer biological pathways (prescribed to
74 patients (34.5%)) were identified. Eight out of the 833 molecules (0.9%),
belonging to six drug families, have been investigated in 28 ongoing or published
clinical trials in combo with radiotherapy. They were prescribed to 63 patients
(29.4%). CONCLUSION: Drug-radiation interaction remains a subject of major
interest, not only for conventional anticancer drugs, but also for NACTs. New
trial designs are thus required.
PMID- 29937211
TI - Long term patient reported swallowing function following chemoradiotherapy for
oropharyngeal carcinoma.
AB - BACKGROUND AND PURPOSE: Limited data are available to inform on long term
swallowing outcomes following concurrent chemoradiotherapy for oropharyngeal
carcinoma. The aims of this study are to determine long term patient-reported
swallowing outcomes across two large UK centres in routine clinical practice and
identify associated factors. MATERIAL AND METHODS: All patients treated for
oropharyngeal squamous cell carcinoma with concurrent chemoradiotherapy, and
irradiation of the bilateral neck, between 2011 and 2013 were identified. Those
requiring therapeutic enteral feeding prior to treatment, or having subsequent
disease relapse, were excluded from the study. Patients were sent postal
invitations to complete the MD Anderson Dysphagia Inventory (MDADI), at least two
years following completion of treatment. RESULTS: Completed MDADI were received
from 201/242 eligible patients (83%) at a median of 3.4 years (range 2-5) post
treatment. Median composite MDADI score was 68.4. 64 (32%) had composite MDADI
<60 classed as 'poor' function, 76 (38%) scores >=60-<80 classed as adequate
function, and 61 (31%) had scores >=80 classed as optimal function. Patients with
normal and abnormal pre-treatment diet had median composite MDADI scores of 70.5
versus 47.4 respectively. Patients who did not require enteral feeding during
treatment and those who did had median composite MDADI scores of 76.3 versus 65.3
respectively. On multivariate analysis poorer performance status, abnormal pre
treatment diet, and use of enteral feeding during radiotherapy were all
significantly associated with lower composite, global and subscale MDADI scores.
CONCLUSIONS: Patient reported swallowing dysfunction remains common in the long
term post-chemoradiotherapy. Impaired pre-treatment diet and use of enteral
feeding during treatment are key factors associated with poorer swallowing
outcomes.
PMID- 29937212
TI - Survival gain with re-Op/RT for recurred high-grade gliomas depends upon risk
groups.
AB - INTRODUCTION: A majority of high-grade gliomas relapse despite combined surgery,
radiotherapy and chemotherapy. There is no consensus on standard treatment for
recurrent high-grade gliomas, or defined efficacy of adjuvant re-RT after re-Op.
This retrospective study evaluated the benefit and safety of re-RT after re-Op
(re-Op/RT). MATERIALS AND METHODS: A total of 84 patients with recurrent high
grade gliomas who underwent reoperation from 2009 to 2015 were analyzed. All
patients received neurosurgical intervention and adjuvant radiotherapy previously
before recurrence. At recurrence and after reoperation, treatment options were
discussed in multidisciplinary clinic or brain tumor joint conference. For re-RT,
cumulative EQD2 (equivalent dose in 2 Gy fractions at alpha/beta = 2) was below
106.9 Gy. RESULT: Median progression free survival (PFS) was 6.5 months; 3.5
months with re-Op, 9.0 months with re-Op/RT (p = 0.025). Age <50, time interval
to recur >=12 months, WHO pathologic grade III, methylated MGMT promotor, and re
RT were factors enhancing PFS in the multivariate analysis. Median overall
survival (OS) was 18.3 months: 12.7 months with re-Op, and 28.1 months with re
Op/RT (p = 0.066). Three risk factors (age >50, WHO grade IV, and unmethylated
promoter of MGMT) were significantly associated with poor OS in multivariate
analysis. Benefit of re-RT in both OS and PFS was established in patients
carrying 2 or more risk factors. During re-RT, 4 patients (8%) had grade 2 or
higher toxicity, and 3 patients (6%) did not complete re-RT. No radionecrosis was
observed. CONCLUSION: Re-RT after re-Op was tolerable with a cumulative median
EQD2 of 99.3 Gy and resulted in clear benefit in PFS and marginal gain in OS.
Survival gain with re-Op/RT was more prominent in patients with two or more risk
factors (age >=50, WHO pathologic grade IV, unmethylated MGMT promoter), and
needs to be validated.
PMID- 29937213
TI - Safety concerns regarding ablative radiotherapy for ventricular tachycardia.
PMID- 29937215
TI - Extracellular DNA in plasma: From marking to dissecting the cell biology of
cardiac transplants.
PMID- 29937214
TI - GLP-2 receptor signaling controls circulating bile acid levels but not glucose
homeostasis in Gcgr-/- mice and is dispensable for the metabolic benefits ensuing
after vertical sleeve gastrectomy.
AB - OBJECTIVE: Therapeutic interventions that improve glucose homeostasis such as
attenuation of glucagon receptor (Gcgr) signaling and bariatric surgery share
common metabolic features conserved in mice and humans. These include increased
circulating levels of bile acids (BA) and the proglucagon-derived peptides
(PGDPs), GLP-1 and GLP-2. Whether BA acting through TGR5 (Gpbar1) increases PGDP
levels in these scenarios has not been examined. Furthermore, although the
importance of GLP-1 action has been interrogated in Gcgr-/- mice and after
bariatric surgery, whether GLP-2 contributes to the metabolic benefits of these
interventions is not known. METHODS: To assess whether BA acting through Gpbar1
mediates improved glucose homeostasis in Gcgr-/- mice we generated and
characterized Gcgr-/-:Gpbar1-/- mice. The contribution of GLP-2 receptor (GLP-2R)
signaling to intestinal and metabolic adaptation arising following loss of the
Gcgr was studied in Gcgr-/-:Glp2r-/- mice. The role of the GLP-2R in the
metabolic improvements evident after bariatric surgery was studied in high fat
fed Glp2r-/- mice subjected to vertical sleeve gastrectomy (VSG). RESULTS:
Circulating levels of BA were markedly elevated yet similar in Gcgr-/-:Gpbar1+/+
vs. Gcgr-/-:Gpbar1-/- mice. Loss of GLP-2R lowered levels of BA in Gcgr-/- mice.
Gcgr-/-:Glp2r-/- mice also exhibited shifts in the proportion of circulating BA
species. Loss of Gpbar1 did not impact body weight, intestinal mass, or glucose
homeostasis in Gcgr-/- mice. In contrast, small bowel growth was attenuated in
Gcgr-/-:Glp2r-/- mice. The improvement in glucose tolerance, elevated circulating
levels of GLP-1, and glucose-stimulated insulin levels were not different in Gcgr
/-:Glp2r+/+ vs. Gcgr-/-:Glp2r-/- mice. Similarly, loss of the GLP-2R did not
attenuate the extent of weight loss and improvement in glucose control after VSG.
CONCLUSIONS: These findings reveal that GLP-2R controls BA levels and relative
proportions of BA species in Gcgr-/- mice. Nevertheless, the GLP-2R is not
essential for i) control of body weight or glucose homeostasis in Gcgr-/- mice or
ii) metabolic improvements arising after VSG in high fat-fed mice. Furthermore,
despite elevations of circulating levels of BA, Gpbar1 does not mediate elevated
levels of PGDPs or major metabolic phenotypes in Gcgr-/- mice. Collectively these
findings refine our understanding of the relationship between Gpbar1, elevated
levels of BA, PGDPs, and the GLP-2R in amelioration of metabolic derangements
arising following loss of Gcgr signaling or after vertical sleeve gastrectomy.
PMID- 29937216
TI - [Ultrasound-guided transversus abdominis plane block in patients undergoing
laparoscopic cholecystectomy: comparison of efficacy of bupivacaine and
levobupivacaine on postoperative pain control].
AB - BACKGROUND AND OBJECTIVE: The use of transversus abdominis plane block with
different local anesthetics is considered as a part of multimodal analgesia
regimen in laparoscopic cholecystectomy patients. However no studies have been
published comparing bupivacaine and levobupivacaine for transversus abdominis
plane block. We aimed to compare bupivacaine and levobupivacaine in ultrasound
guided transversus abdominis plane block in patients undergoing laparoscopic
cholecystectomy. METHODS: Fifty patients (ASA I/II), undergoing laparoscopic
cholecystectomy were randomly allocated into two groups. Following anesthesia
induction, ultrasound-guided bilateral transversus abdominis plane block was
performed with 30mL of bupivacaine 0.25% in Group B (n=25) and 30mL of
levobupivacaine 0.25% in Group L (n=25) for each side. The level of pain was
evaluated using 10cm visual analog scale (VAS) at rest and during coughing 1, 5,
15, 30min and 1, 2, 4, 6, 12 and 24h after the operation. When visual analogue
scale>3, the patients received IV tenoxicam 20mg. If visual analogue scale
remained >3, they received IV. tramadol 1mg.kg-1. In case of inadequate
analgesia, a rescue analgesic was given. The analgesic requirement, time to first
analgesic requirement was recorded. RESULTS: Visual analogue scale levels showed
no difference except first and fifth minutes postoperatively where VAS was higher
in Group L (p<0.05). Analgesic requirement was similar in both groups. Time to
first analgesic requirement was shorter in Group L (4.35+/-6.92min vs. 34.91+/
86.26min, p=0.013). CONCLUSIONS: Bupivacaine and levobupivacaine showed similar
efficacy at TAP block in patients undergoing laparoscopic cholecystectomy.
PMID- 29937217
TI - Corrigendum to "Childhood Adversity and Adult Depression among the Incarcerated:
Differential Exposure and Vulnerability by Race/Ethnicity and Gender." [Child
Abuse and Neglect, 2014, 38: 1409-1420].
PMID- 29937218
TI - Gout and arrhythmias: In search for causation beyond association.
AB - Gout is a systemic disease, characterized by the formation and deposition of
crystals in tissues (mainly in and around the joints) of individuals with
elevated serum uric acid levels. Lately, a considerable number of reports
relating elevated uric acid and/or gout with rhythm disorders, such as atrial
fibrillation, have been published. This review summarizes evidence linking common
arrhythmias and hyperuricemia/gout and discusses questions or controversies that
surround it. Overall, existing evidence may not be overwhelming, but strongly
suggests a positive correlation between uric acid levels and common rhythm
disorders. Needless to say that such a link - as a univariate association between
the two - is to be expected, given the extensive overlap of risk factors and
comorbidities of hyperuricemia/gout and arrhythmias. However, the observed
associations seem to persist - in most studies - after extensive adjustment for
potential confounders. Still, multivariable analyses of epidemiologically
collected data cannot substitute for proof coming from basic and clinical
studies. There is obviously a need for further basic research to establish a
causal relationship between uric acid effects and arrhythmias, as well as
translational studies and clinical trials to investigate the therapeutic
implications of such a relationship. Simply put, we are fairly certain that there
is association, but proof of causation is what we are still in want of.
PMID- 29937219
TI - Comparison of Unmatched Pairs and Possible Impact on Result Interpretation.
PMID- 29937220
TI - Prosthesis-Patient Mismatch: When Should It Be Determined for Prognosis
Implications?
PMID- 29937221
TI - The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2018 Update on
Research: Outcomes Analysis, Quality Improvement, and Patient Safety.
AB - The Society of Thoracic Surgeons Adult Cardiac Database (ACSD) is an
international voluntary registry that provides adult cardiac surgery programs
with risk-adjusted outcome reports for quality improvement. With more than
6,300,000 procedural records in adult cardiac surgery, the ACSD has proven to be
a leading instrument for clinical outcomes research. The ACSD generated numerous
major original contributions that were either published or accepted for
publication in 2017. These works significantly contributed to the practice of
adult cardiac surgery through outcome measurement and quality improvement. This
paper summarizes the recent ACSD contributions to the literature.
PMID- 29937222
TI - Multicenter study establishing the clinical validity of a nucleic-acid
amplification-based assay for the diagnosis of bacterial vaginosis.
AB - The present study sought to validate the clinical performance of a previously
described PCR-based assay for the diagnosis of bacterial vaginosis (BV). A total
of 1579 patients were enrolled in 5 locations; samples were classified as BV
positive (n=538) or negative (n=1,041) based on an algorithm utilizing
quantitative Gram-stain analysis of vaginal discharge and clinical evaluation
(Amsel criteria); a next-generation sequencing (NGS) approach to determining
diversity of vaginal microbiota was used to resolve discordant results between BV
PCR and Nugent/Amsel. BV-PCR demonstrated a sensitivity of 96.0% (483/503) and a
specificity of 90.2% (885/981) when measured against the conventional test
standard, with 95 samples (6.0%) being classified as indeterminate. After
resolution of discordant results by NGS, including elimination of the PCR
indeterminate category, the resolved sensitivity, specificity, and positive and
negative predictive values of the BV-PCR assay were 98.7%, 95.9%, 92.9%, and
96.9%, respectively. The results of this study conclusively demonstrate that a
relatively simple, 3-biomarker, molecular amplification construct can effectively
diagnose BV in symptomatic women. Results generated using this assay were
congruent with those obtained using conventional and molecular reference methods.
PMID- 29937223
TI - mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm
by Tuning Crowding.
AB - Macromolecular crowding has a profound impact on reaction rates and the physical
properties of the cell interior, but the mechanisms that regulate crowding are
poorly understood. We developed genetically encoded multimeric nanoparticles
(GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a
fluorescent protein that self-assemble into bright, stable particles of defined
size and shape. By combining tracking of GEMs with genetic and pharmacological
approaches, we discovered that the mTORC1 pathway can modulate the effective
diffusion coefficient of particles >=20 nm in diameter more than 2-fold by tuning
ribosome concentration, without any discernable effect on the motion of molecules
<=5 nm. This change in ribosome concentration affected phase separation both in
vitro and in vivo. Together, these results establish a role for mTORC1 in
controlling both the mesoscale biophysical properties of the cytoplasm and
biomolecular condensation.
PMID- 29937224
TI - Immunomimetic Designer Cells Protect Mice from MRSA Infection.
AB - Many community- and hospital-acquired bacterial infections are caused by
antibiotic-resistant pathogens. Methicillin-resistant Staphylococcus aureus
(MRSA) predisposes humans to invasive infections that are difficult to eradicate.
We designed a closed-loop gene network programming mammalian cells to
autonomously detect and eliminate bacterial infections. The genetic circuit
contains human Toll-like receptors as the bacterial sensor and a synthetic
promoter driving reversible and adjustable expression of lysostaphin, a
bacteriolytic enzyme highly lethal to S. aureus. Immunomimetic designer cells
harboring this genetic circuit exhibited fast and robust sense-and-destroy
kinetics against live staphylococci. When tested in a foreign-body infection
model in mice, microencapsulated cell implants prevented planktonic MRSA
infection and reduced MRSA biofilm formation by 91%. Notably, this system
achieved a 100% cure rate of acute MRSA infections, whereas conventional
vancomycin treatment failed. These results suggest that immunomimetic designer
cells could offer a therapeutic approach for early detection, prevention, and
cure of pathogenic infections in the post-antibiotic era.
PMID- 29937225
TI - A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.
AB - Transposable elements represent nearly half of mammalian genomes and are
generally described as parasites, or "junk DNA." The LINE1 retrotransposon is the
most abundant class and is thought to be deleterious for cells, yet it is
paradoxically highly expressed during early development. Here, we report that
LINE1 plays essential roles in mouse embryonic stem cells (ESCs) and pre
implantation embryos. In ESCs, LINE1 acts as a nuclear RNA scaffold that recruits
Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a
transcriptional program specific to the 2-cell embryo. In parallel, LINE1 RNA
mediates binding of Nucleolin and Kap1 to rDNA, promoting rRNA synthesis and ESC
self-renewal. In embryos, LINE1 RNA is required for Dux silencing, synthesis of
rRNA, and exit from the 2-cell stage. The results reveal an essential partnership
between LINE1 RNA, Nucleolin, Kap1, and peri-nucleolar chromatin in the
regulation of transcription, developmental potency, and ESC self-renewal.
PMID- 29937226
TI - LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade.
AB - Chromatin regulators play a broad role in regulating gene expression and, when
gone awry, can lead to cancer. Here, we demonstrate that ablation of the histone
demethylase LSD1 in cancer cells increases repetitive element expression,
including endogenous retroviral elements (ERVs), and decreases expression of RNA
induced silencing complex (RISC) components. Significantly, this leads to double
stranded RNA (dsRNA) stress and activation of type 1 interferon, which stimulates
anti-tumor T cell immunity and restrains tumor growth. Furthermore, LSD1
depletion enhances tumor immunogenicity and T cell infiltration in poorly
immunogenic tumors and elicits significant responses of checkpoint blockade
refractory mouse melanoma to anti-PD-1 therapy. Consistently, TCGA data analysis
shows an inverse correlation between LSD1 expression and CD8+ T cell infiltration
in various human cancers. Our study identifies LSD1 as a potent inhibitor of anti
tumor immunity and responsiveness to immunotherapy and suggests LSD1 inhibition
combined with PD-(L)1 blockade as a novel cancer treatment strategy.
PMID- 29937227
TI - The Inner Nuclear Membrane Is a Metabolically Active Territory that Generates
Nuclear Lipid Droplets.
AB - The inner nuclear membrane (INM) encases the genome and is fused with the outer
nuclear membrane (ONM) to form the nuclear envelope. The ONM is contiguous with
the endoplasmic reticulum (ER), the main site of phospholipid synthesis. In
contrast to the ER and ONM, evidence for a metabolic activity of the INM has been
lacking. Here, we show that the INM is an adaptable membrane territory capable of
lipid metabolism. S. cerevisiae cells target enzymes to the INM that can promote
lipid storage. Lipid storage involves the synthesis of nuclear lipid droplets
from the INM and is characterized by lipid exchange through Seipin-dependent
membrane bridges. We identify the genetic circuit for nuclear lipid droplet
synthesis and a role of these organelles in regulating this circuit by
sequestration of a transcription factor. Our findings suggest a link between INM
metabolism and genome regulation and have potential relevance for human
lipodystrophy.
PMID- 29937228
TI - The Effect of the Pain Symptom Cluster on Performance in Women Diagnosed with
Advanced Breast Cancer: The Mediating Role of the Psychoneurological Symptom
Cluster.
AB - BACKGROUND: Pain, depression, anxiety, sleep disturbances, and constipation were
reported in different symptom clusters at different stages of breast cancer.
Managing symptom clusters rather than individual symptoms can improve performance
status. AIM: The study examined the effect of pain symptom cluster (pain and
constipation) on performance when mediated by the psychoneurological symptom
cluster (depression, anxiety, and sleep disturbances) using age as a moderator.
DESIGN: A secondary analysis. SETTINGS: Palliative care center at a tertiary
medical center in northeast Ohio. PARTICIPANTS: Eighty-six women diagnosed with
advanced breast cancer. METHOD: A quantitative cross-sectional approach. RESULTS:
Ordinal logistic regression showed that pain symptom cluster did not have a
significant mediation effect on performance. Odds ratio indicated that subjects
with pain symptom cluster were 63% more likely to be bedridden (odds ratio =
1.63, confidence interval = .69-3.84). Women who reported pain symptom cluster
were 5% more likely to have psychoneurological symptom cluster (odds ratio =
1.05, confidence interval = .400-2.774). Stratified analysis of age showed no
differences in performance. Post-hoc analysis showed that the components of pain
symptom cluster had a significant effect on psychoneurological symptom cluster
(odds ratio: 3 [1.18-7.62]). CONCLUSIONS: Pain, constipation, depression,
anxiety, and sleep disturbances were highly prevalent in women with advanced
breast cancer. However, they tended to cluster in different symptom clusters.
Although some findings were not significant, they all supported the direction of
the tested hypotheses. Variations in symptom clusters research, including
methodology, instruments, statistical tests, and chosen symptom cluster
correlation coefficient, should be addressed.
PMID- 29937229
TI - Postoperative Pain Management: A Bedside Perspective.
AB - PURPOSE: Postoperative pain management is an ongoing challenge in surgical care,
during which inadequate relief can contribute to postoperative complications, and
nurses are key figures in this process. The aim of the present study was to gain
knowledge of how nurses provide postoperative pain management for women
undergoing major surgery for endometriosis. DESIGN: An ethnographic field study,
consisting of semi-structured interviews and participant observations, was
conducted in a setting of 2 gynecological units within a large Scandinavian
university hospital. METHOD: The participants were mainly nurses and patients.
The overall focus for the field observations and interviews was on how the
participants interacted and made care decisions concerning pain. The analysis
focused on nurse-patient interaction in postoperative bedside care. A principal
theme, pain-related nursing practice emerged, together with the sub-themes nurse
patient interaction, interpretation and assessment of pain and pain management,
which represented a circular process, identified in bedside practice.
CONCLUSIONS: To some extend the postoperative pain management was influenced by
unexpressed health beliefs and routine actions, and patient involvement was not
prominent. Furthermore, the existing guidelines for pain management did not seem
useful to the nurses. CLINICAL IMPLICATIONS: There is a need to develop a new and
more practice-oriented postoperative pain management, in ways that also integrate
the patient experience.
PMID- 29937230
TI - Polyphenols at interfaces.
AB - Polyphenols are important molecules in living organisms, particularly in plants,
where they serve as protectants against predators. They are also of fundamental
importance in pharmacology for their antioxidant and antibacterial activities.
Since a few years polyphenols are also used in surface functionalization
mimicking the tannin deposition observed when tea or red wine are in contact with
the surface of cups or glasses respectively. The interaction of polyphenols with
proteins to yield colloids and of polyphenol with surfaces will be reviewed in
this article to provide an overview of such particles and surface
functionalization methods in modern surface science. Particular emphasis will be
given to biological applications of polyphenols at interfaces.
PMID- 29937231
TI - Reply to: Valid assessment of Women's satisfaction with breast cancer screening
programs.
PMID- 29937232
TI - Diabetes Risk in Childhood Cancer Survivors: A Population-Based Study.
AB - OBJECTIVE: With continued improvements in survival following childhood cancer,
the long-term health consequences of cancer treatments are receiving greater
focus. Diabetes is emerging as a potential late effect of cancer therapy;
however, the magnitude of risk has not been well established. The goal of our
study was to evaluate the risk for diabetes in childhood cancer survivors in
Ontario using validated population-based databases. METHODS: We used provincial
administrative health databases to compare the rate of diabetes in childhood
cancer survivors and controls from the general population. Diabetes was measured
using a validated algorithm. We used a cause-specific hazard regression model in
which death and development of another cancer were treated as competing risks.
RESULTS: We identified 10,438 1-year survivors of childhood cancer that were
diagnosed before age 21 between January 1, 1990, and December 31, 2010. The mean
follow up was 11.2 years (standard deviation, 6.9). Cancer survivors had a 55%
increased rate of developing diabetes compared with matched controls (HR 1.51,
95% CI 1.28 to 1.78) in models adjusted for rurality and income. Individuals
treated for cancer between ages 6 and 10 had the highest increased rates of
diabetes (HR 3.89, CI 2.26 to 6.68). Among cancer types, leukemia and lymphoma
were associated with the greatest increased risk for diabetes. CONCLUSIONS: Our
study supports evidence of an increased risk for diabetes in survivors of
childhood cancer. Future research is warranted for better identification of
treatment-related risk factors for diabetes in this population.
PMID- 29937233
TI - The cocaine cutting agent levamisole is frequently detected in cocaine users.
AB - Cocaine use in Australia is increasing, with approximately 2.5% of the surveyed
population having used cocaine. In the USA, levamisole, a widely used anti
helminthic veterinary drug has been increasingly detected as a cutting agent in
cocaine seizures. Levamisole is known to cause agranulocytosis in humans. We
ascertained the prevalence of levamisole-adulterated cocaine, detectable in the
urine from patients that had undergone a pathology request for a urine drug
screen. We assayed routinely requested urines that were positive for cocaine on
immunoassay with liquid chromatography high resolution quadrupole time of flight
mass spectrometry (LC-QToF). We investigated available urine samples from a
period of 2 years that had a positive result for cocaine. In addition, we
examined samples that were below the cut-off for cocaine on immunoassay.
Specimens were analysed for the presence of levamisole and other 'unknown' drugs.
In the period under investigation the laboratory examined 3665 urine samples for
cocaine: 1.4% (n = 51) of the samples were positive for cocaine by immunoassay
and half of these (n = 26, 51%) were further examined by LC-QToF. In addition, we
examined 10 samples that were negative by immunoassay (as defined by AS/NZS
4308:2008). Levamisole was detected in the urine of cocaine users in
approximately 75% of cases. Other illicit drugs were also frequently found in
this cohort. The most common illicit drugs detected were methamphetamine, ecstasy
and cannabis. Australian cocaine is widely adulterated with levamisole. Cocaine
users are at risk of levamisole related health problems in addition to the
problems related to cocaine.
PMID- 29937234
TI - Metastatic spermatocytic tumour with hybrid genetics: breaking the rules in germ
cell tumours.
PMID- 29937235
TI - Liver reirradiation for patients with hepatocellular carcinoma and liver
metastasis.
AB - PURPOSE: This study aimed to assess the safety and efficacy of administering
liver reirradiation to patients with primary liver tumors or liver metastasis.
METHODS AND MATERIALS: A total of 49 patients (with 64 individual tumors) who
received liver reirradiation at our institution between June 2008 and December
2016 were identified for retrospective review. Patients were treated to the same,
different, or a combination of previously treated liver tumors for recurrent
primary (53%) or metastatic (47%) disease using photons or protons. Clinical and
treatment-related factors were compiled and patients were monitored for toxicity
and evidence of classic or nonclassic radiation-induced liver disease. Survival
was estimated with the Kaplan-Meier method and cumulative incidence of local
failure (LF) was used to estimate LF using the Response Evaluation Criteria in
Solid Tumors version 1.1. RESULTS: The median age at the time of reirradiation
was 72 years and the median interval between radiation courses was 9 months. At a
median follow-up of 10.5 months, 36 patients (73%) had died, 9 patients (18%)
were alive, and 4 patients (8%) were lost to follow-up. The median survival for
the cohort was 14 months. The overall 1-year estimate of LF was 46.4%. The 1-year
estimates of LF for liver metastases and hepatocellular carcinoma were 61.0% and
32.5%, respectively. The average prescription dose was similar between the
reirradiation and initial courses (equivalent dose in 2 Gy fractions EQD2: 65.0
vs 64.3 Gyalpha/beta = 10, respectively) but the average dose to the untreated
liver was lower at the time of reirradiation (EQD2: 10.5 vs 13.9 Gyalpha/beta =
3, respectively, P = .01). Among patients with hepatocellular carcinoma, the
average normal liver dose was significantly larger for patients who exhibited a
worsening of Child-Pugh score after reirradiation compared with those who did not
(1210 cGy vs 759 cGy, P = .04). With regard to toxicity, 85.7% of patients
experienced grade 1 to 2 toxicity, 4.1% developed grade 3, and only 2 patients
(4.1%) met the criteria for radiation-induced liver disease after reirradiation.
CONCLUSIONS: Liver reirradiation may be an effective and safe option for select
patients; however, further prospective study is necessary to establish treatment
guidelines and recommended dosing.
PMID- 29937236
TI - Universal screening at age 1-2 years as an adjunct to cascade testing for
familial hypercholesterolaemia in the UK: A cost-utility analysis.
AB - BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is widely
underdiagnosed. Cascade testing (CT) of relatives has been shown to be feasible,
acceptable and cost-effective in the UK, but requires a supply of index cases.
Feasibility of universal screening (US) at age 1-2 years was recently
demonstrated. We examined whether this would be a cost-effective adjunct to CT in
the UK, given the current and plausible future undiagnosed FH prevalence.
METHODS: Seven cholesterol and/or mutation-based US +/- reverse cascade testing
(RCT) alternatives were compared with no US in an incremental analysis with a
healthcare perspective. A decision model was used to estimate costs and outcomes
for cohorts exposed to the US component of each strategy. RCT case ascertainment
was modelled using recent UK CT data, and probabilistic Markov models estimated
lifetime costs and health outcomes for the cohorts screened under each
alternative. 1000 Monte Carlo simulations were run for each model, and average
outcomes reported. Further uncertainty was explored deterministically. Threshold
analysis investigated the association between undiagnosed FH prevalence and cost
effectiveness. RESULTS: A strategy involving cholesterol screening followed by
diagnostic genetic testing and RCT was the most cost-effective modelled
(incremental cost-effectiveness ratio (ICER) versus no US L12,480/quality
adjusted life year (QALY); probability of cost-effectiveness 96.8% at
L20,000/QALY threshold). Cost-effectiveness was robust to both deterministic
sensitivity analyses and threshold analyses that modelled ongoing case
ascertainment at theoretical maximum levels. CONCLUSIONS: These findings support
implementation of universal cholesterol screening followed by diagnostic genetic
testing and RCT for FH, under a UK conventional willingness-to-pay threshold.
PMID- 29937237
TI - Are Corticosteroids Beneficial in the Treatment of Community-Acquired Pneumonia?
PMID- 29937238
TI - A Comparative Effectiveness Study of Two Nontargeted HIV and Hepatitis C Virus
Screening Algorithms in an Urban Emergency Department.
AB - STUDY OBJECTIVE: We compare the effectiveness of 2 nontargeted HIV and hepatitis
C virus screening protocols integrated consecutively into care in an urban
emergency department: a nurse-order HIV/hepatitis C virus screening algorithm
followed by an automated-laboratory-order HIV/hepatitis C virus screening
algorithm programmed into the electronic health record. METHODS: This was a
before-after comparative effectiveness cohort study. All patients aged 18 to 75
years who received treatment during 5-month periods were eligible for
participation. The main outcome measures were the number of patients screened and
the number with newly diagnosed HIV and hepatitis C virus infection. RESULTS: Of
the eligible patients, 6,736 (33.9%) completed HIV screening during the automated
laboratory-order HIV/hepatitis C virus screening algorithm, whereas 4,121 (19.6%)
completed HIV screening during the nurse-order HIV/hepatitis C virus screening
algorithm (difference 14.3%; 95% confidence interval 13.4% to 15.1%); and 6,972
(35.1%) completed hepatitis C virus screening during the automated-laboratory
order HIV/hepatitis C virus screening algorithm, whereas 2,968 (14.2%) completed
hepatitis C virus screening during the nurse-order HIV/hepatitis C virus
screening algorithm (difference 20.9%; 95% confidence interval 20.1% to 21.7%).
More patients had newly diagnosed HIV (23 versus 17) and hepatitis C virus
infection (101 versus 29) during the automated-laboratory-order HIV/hepatitis C
virus screening algorithm than the nurse-order HIV/hepatitis C virus screening
algorithm. Results were more often available before discharge (HIV 87.2% versus
65.1%; hepatitis C virus 90.0% versus 65.4%) and fewer patients underwent
repeated screening (HIV 1.6% versus 5.8%; hepatitis C virus 1.3% versus 4.5%)
during the automated-laboratory-order HIV/hepatitis C virus screening algorithm
than the nurse-order HIV/hepatitis C virus screening algorithm. CONCLUSION: An
electronic health record algorithm that automatically links HIV/hepatitis C virus
screening to laboratory ordering for adult patients is more effective than a
nurse-driven protocol. With widespread use of electronic health record systems,
this model can be easily replicated and should be considered the standard for
future programs.
PMID- 29937239
TI - Personality Traits of Children With Vocal Fold Nodules.
AB - This is a case-control study investigating the personality profiles of children
with vocal fold nodules (VFNs). Personality has been suggested as a contributing
factor to VFN in adults and in children. However, previous studies in children
have focused on psychopathologic traits and have reported contradictory findings.
The aim of our study was to explore whether general, nonpathologic personality
structure predicts the presence of VFN in children. Personality traits were
measured in 34 children with VFN, aged 6.0-13.6, and 34 age- and sex-matched
normophonic controls by means of a pediatric five-factor personality
questionnaire. Children with VFN were found to be significantly more extroverted
than controls (P = 0.022, d = 0.61), and a binary logistic regression showed that
extraversion significantly predicted the presence of VFN in our population (P =
0.027). The clinical implications of the results are discussed.
PMID- 29937240
TI - Satiety and gastrointestinal hormones during a Mixed Meal Tolerance Test after
gastric bypass surgery: association with plasma amino acid concentrations.
AB - BACKGROUND: Circulating amino acids have been associated with both appetite and
the secretion of anorexigenic hormones in healthy and obese populations. This
effect has not been investigated in subjects having undergone Roux-en-Y gastric
bypass surgery (RYGB). OBJECTIVE: To investigate the association between
postprandial plasma concentrations of amino acids and the anorexigenic hormones
glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY), the
orexigenic hormone ghrelin, and satiety and hunger in post-RYGB subjects.
SETTING: A Dutch surgical department. METHODS: Participants after primary RYGB
were studied during a Mixed Meal Tolerance Test (MMTT). Satiety and hunger were
assessed every 30 minutes on visual analogue scales. Blood samples were collected
at baseline, every 10 minutes during the first half hour and every 30 minutes
until 210 minutes after the start. The samples were assessed for 24 amino acids
and 3 gastrointestinal hormones. Incremental areas under the curve (iAUCs) were
calculated. Exploratory analyses were performed in which subjects were divided
into high and low responders depending on the median iAUC. RESULTS: 42 subjects,
aged 48 +/- 11 (mean +/- SD) years, 31 to 76 months post-RYGB and with total
weight loss of 30 +/- 9% completed the MMTT. Subjects with high satiety scores
had more than a 25% higher net iAUC of PYY and GLP-1 and at least a 10% higher
net iAUC of 10 amino acids compared to subjects with low scores (P < 0.05). The
net iAUC of five of these amino acids (i.e. arginine, asparagine, histidine,
serine and threonine) was more than 10% higher in subjects with high responses on
GLP-1 and/or PYY (P < 0.05). CONCLUSIONS: Certain postprandial amino acids were
associated with satiety and anorexigenic hormones and could therefore play a role
in appetite regulation after RYGB; either by a direct effect on satiety,
indirectly through gastrointestinal hormones, or both.
PMID- 29937241
TI - Relationship between bariatric surgery and periodontal status: a systematic
review and meta-analysis.
AB - BACKGROUND: The effects of bariatric surgery can reflect in the oral cavity and
can cause alterations in oral health. This high prevalence of oral alterations in
the pre and post-operative periods has been highlighted in different studies.
OBJECTIVES: To investigate the effect of bariatric surgery on periodontal status
through a systematic review. METHODS: Electronic search was conducted in PubMed,
VHL, Web of Science, Science direct, Scopus, and Cochrane databases through May
2017. Manual search, gray literature, and counter-refence of included articles
were also conducted. Eligibility criteria included observational studies that
reported periodontal outcomes before and after bariatric surgery. RESULTS: Search
strategy resulted in 1878 articles. Following the selection process, nine studies
were included in the qualitative analysis and five in the meta-analysis. Three
cross-sectional studies showed risk of bias score ranging from 5 to 6 stars, and
Cohort studies scored from 6 to 9 stars out of 9 possible stars on the Newcastle
Ottawa scale. The quantitative analysis showed that clinical attachment level
(MD: 0.07; CI95% -0.17 to 0.31), gingival index (MD: -0.28; CI95% -1.68 to 1.11),
percentage of bleeding sites (MD: -0.21; CI95% -0.77 to 0.35), and pocket probing
depth (MD: 0.08 CI95% -0.14 to 0.31) were not different before and after
bariatric surgery. However, the plaque index was lower after than before
bariatric surgery (MD: -1.29; CI 95% -2.34 to -0.24). CONCLUSIONS: Plaque index
can be improved after bariatric surgery. The present systematic review
investigated the association between bariatric surgery and periodontal status
from cross-sectional and longitudinal studies. A systematic search strategy was
developed until May 2017. The results of this systematic review allowed the
conclusion that the plaque index can be improved after bariatric surgery.
PMID- 29937242
TI - Cutaneous metastases from neuroendocrine carcinoma of the cervix-An unusual
metastatic lesion from an uncommon malignancy.
AB - Neuroendocrine carcinoma (NEC) is an uncommon and aggressive type of small cell
cervical cancer. NECs mostly arise from gastro-entero-pancreatic tract and the
lung, but rarely from other organs like cervix. NEC of the cervix is a rare
malignancy and constitutes 0.9%-1.5% of cervical tumors. NECs of cervix are
common in perimenopausal females and present with abnormal vaginal bleeding and
mimic squamous cell cancers, usually with no distinguishing features. On
Immunohistochemistry, presence of chromogranin, synaptophysin, and CD-56 is
necessary to make a diagnosis of small cell carcinoma. These tumors are notorious
for local as well as distant relapses in comparison to their squamous and
adenocarcinoma counterpart. NECs are characterized by highly aggressive clinical
behavior and carry a poor prognosis. They commonly metastases to lung, liver,
brain, and bones even in early stages of the disease. Metastasis to skin is a
rare occurrence. We herein report a case of a NEC of the uterine cervix with
multiple cutaneous metastases. After the initial diagnosis of NEC of cervix, the
patient received concurrent chemoradiation followed by intracavitary
brachytherapy. On subsequent follow-up, the patient developed multiple cutaneous
metastasis along with liver metastases. This case is reported in view of rarity
of the case with skin metastases. To the best of our knowledge, only 3 cases of
cutaneous metastases from NEC of the cervix are reported till date. Being a rare
malignancy, evidence in the literature is in form of case reports and small case
series. Thus, the optimal treatment strategy varies for these patients.
Multimodality management with teamwork is necessary to manage individual
patients.
PMID- 29937243
TI - Lack of impact of rotavirus vaccination on childhood seizure hospitalizations in
England - An interrupted time series analysis.
AB - Observational studies have linked a reduction in childhood seizures (CS) to the
introduction of rotavirus vaccination (RV). England is opportunely placed to
explore this due to well-defined introduction, high uptake of RV and centralised
Hospital Episodes Statistics recording all admissions. We investigated the
association between seizures and vaccine use through interrupted time-series
analysis of all CS admissions in children <3 years old (ICD-10 codes; G40*-G41*,
R56.0*) during 2007-2017. We did not detect a statistically significant
association between the introduction of RV and admission with febrile (p = 0.84),
afebrile (p = 0.83) or all CS (p = 0.93), even when limited to peak rotavirus
seasonality (March). This is the first ecological study in a country that
exclusively uses the monovalent vaccine. Although a negative finding, we would
argue that if an effect cannot be detected at this population level then it is
unlikely to be clinically or economically significant but generates hypotheses of
potential non-specific effects.
PMID- 29937244
TI - Seroprevalence of antibodies against the three serotypes of poliovirus and IPV
vaccine response in adult solid organ transplant candidates.
AB - OBJECTIVES: To assess the prevalence of protective antibody titers to
polioviruses in adults candidates for solid organ transplant (SOT), and to assess
the immunogenic response to inactivated polio vaccine in this population.
METHODS: The study included SOT candidates referred to Immunization Reference
Centre of Evandro Chagas National Institute of Infectious Diseases from March
2013 to January 2016. It was conducted in 2 phases. The first one, a cross
sectional seroprevalence study, followed by an uncontrolled analysis of vaccine
response among patients without protective antibody titers at baseline. Antibody
titers to poliomyelitis were determined by microneutralization assay. RESULTS:
Among 206 SOT candidates included, 156 (76%) had protective antibody titers to
all poliovirus serotypes (95% CI: 70-81%). Proven history of oral vaccination in
childhood was not associated with higher seroprevalence of protective antibody.
In 97% of individuals without protective antibody titers at baseline, there was
adequate vaccine response with one dose of inactivated polio vaccine.
CONCLUSIONS: A relevant proportion of adult candidates for SOT does not have
protective titers of antibodies to one or more poliovirus serotype. One dose of
inactivated vaccine elicited protective antibody titers in 97% of these subjects
and should be routinely prescribed prior to SOT.
PMID- 29937245
TI - Serotype distribution of invasive Streptococcus pneumoniae in adults 65 years of
age and over after the introduction of childhood 13-valent pneumococcal conjugate
vaccination programs in Canada, 2010-2016.
AB - The 13-valent conjugate vaccine (PCV13) was recommended for childhood
immunization programs in 2010 in Canada and has decreased the incidence of
invasive pneumococcal disease (IPD) in children and changed the epidemiology of
IPD in adults. This study investigated the epidemiology of IPD in adults 65 years
of age and older in Canada. A total of 7282 invasive S. pneumoniae isolated from
adults >=65 years old were serotyped from 2010 to 2016 and antimicrobial
susceptibility was performed on 2527 isolates. Serotyping was performed by
Quellung reaction using commercial antisera and antimicrobial susceptibilities
were determined by broth microdilution. PCV7 serotypes decreased non
significantly from 2010 to 2016 from 9.1% (n = 96) to 6.7% (n = 72) while the
additional six PCV13 serotypes declined significantly from 39.5% (n = 418) to
18.6% (n = 201) (p < 0.05). The 23-valent pneumococcal polysaccharide vaccine
(PPV23) and non-vaccine (NVT) serotypes increased from 26.3% (n = 278) to 36.2%
(n = 393) (p < 0.05), and from 25.1% (n = 266) to 38.4% (n = 416) (p < 0.05),
respectively. There were no significant changes in antimicrobial resistance rates
from 2011 to 2016: 24.1% of the IPD from adults >=65 years were resistant to
clarithromycin (n = 609), 10.0% to doxycycline (n = 254), 11.8% to penicillin (n
= 299), 5.2% to cefuroxime (n = 131), 6.6% to clindamycin (n = 168), 6.0% to
trimethoprim-sulfamethoxazole (n = 152), and 0.5% (n = 12) to ceftriaxone.
Although overall incidence of IPD in adults >=65 years has remained relatively
constant from 2010 to 2016, childhood PCV13 vaccination programs have been
successful in indirectly reducing IPD caused by PCV13 serotypes in adults through
herd immunity effects.
PMID- 29937246
TI - In Reply: Diaphragmatic Dysfunction Following Cardiac Surgery: Is There a Role
for Pulmonary Ultrasound?
PMID- 29937247
TI - Ethical adoption: A new imperative in the development of technology for dementia.
AB - INTRODUCTION: Technology interventions are showing promise to assist persons with
dementia and their carers. However, low adoption rates for these technologies and
ethical considerations have impeded the realization of their full potential.
METHODS: Building on recent evidence and an iterative framework development
process, we propose the concept of "ethical adoption": the deep integration of
ethical principles into the design, development, deployment, and usage of
technology. RESULTS: Ethical adoption is founded on five pillars, supported by
empirical evidence: (1) inclusive participatory design; (2) emotional alignment;
(3) adoption modelling; (4) ethical standards assessment; and (5) education and
training. To close the gap between adoption research, ethics and practice, we
propose a set of 18 practical recommendations based on these ethical adoption
pillars. DISCUSSION: Through the implementation of these recommendations,
researchers and technology developers alike will benefit from evidence-informed
guidance to ensure their solution is adopted in a way that maximizes the benefits
to people with dementia and their carers while minimizing possible harm.
PMID- 29937248
TI - Superbugs: An Arms Race Against Bacteria.
PMID- 29937249
TI - Past exposures leave a legacy of pulmonary disease in South Korea.
PMID- 29937250
TI - Atezolizumab in patients with metastatic NSCLC.
PMID- 29937251
TI - The Intersection of Implementation Science and Behavioral Health: An Introduction
to the Special Issue.
PMID- 29937252
TI - Supervision in Community Mental Health: Understanding Intensity of EBT Focus.
AB - The goal of the present study was to examine clinician, supervisor, and
organizational factors that are associated with the intensity of evidence-based
treatment (EBT) focus in workplace-based clinical supervision of a specific EBT,
Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). Supervisors (n = 56) and
clinicians (n = 207) from mental health organizations across Washington State
completed online self-report questionnaires. Multilevel modeling (MLM) analyses
were used to examine the relative influence of nested clinician and supervisor
factors on the intensity of EBT focus in supervision. We found that 33% of the
variance in clinician report of EBT supervision intensity clustered at the
supervisor level and implementation climate was the only significant factor
associated with EBT supervision intensity. While individual clinician and
supervisor factors may play a role in EBT coverage in supervision, our results
suggest that an implementation climate that supports EBT may be the most critical
factor for improving intensity of EBT coverage. Thus, implementation efforts that
address the extent to which EBTs are expected, rewarded, and supported within an
organization may be needed to support greater coverage of EBT during workplace
based supervision.
PMID- 29937253
TI - Teacher Job Stress and Satisfaction in Urban Schools: Disentangling Individual-,
Classroom-, and Organizational-Level Influences.
AB - Schools remain among the most frequent providers of children's mental health
services, particularly in low-income urban settings. Several decades of research
have focused on training teachers to implement evidence-based interventions for
minimizing disruptive behavior. Studies consistently demonstrate robust
improvements in student behavior and learning; however, the impact on teachers'
work-related stress or satisfaction is not well understood. Six urban, high
poverty elementary schools were randomly assigned to a school mental health
services model (Links to Learning; L2L) for referred, disruptive students or to
services and professional development as usual (SAU). Teachers (n = 71, K-4
general education teachers) in L2L schools participated in professional
development and consultation in two universal and two targeted interventions to
reduce disruptive behaviors and promote learning. Teachers (n = 65) in SAU
schools participated in professional development as usual. Multiple regression
models examined teacher reports of individual-level self-efficacy, classroom
level student functioning, and school-level organizational health as predictors
of stress and satisfaction. Findings revealed no significant difference between
conditions on teacher work-related stress or satisfaction. Organizational health
was the strongest predictor of stress and satisfaction. Training on and
implementation of evidence-based classroom interventions did not appear to
significantly impact teachers' work-related stress or satisfaction. Instead,
findings point to organizational climate and teacher connectedness as potential
levers for change, supporting prior work on teacher stress and satisfaction in
schools. The significance of targeting organizational factors may be particularly
significant in urban school districts.
PMID- 29937254
TI - A Mixed Methods Study of the Stages of Implementation for an Evidence-Based
Trauma Intervention in Schools.
AB - A mixed methods study was conducted to examine the implementation process of 26
urban school-based mental health clinics that took part in a training and
implementation support program for an evidence-based school trauma intervention.
Implementation process was observed using the Stages of Implementation Completion
(SIC) measure. Qualitative interviews were conducted with clinic leaders in order
to gain insight into clinic processes related to the SIC. Results showed that
almost all of the clinics engaged in some activities related to pre
implementation (engagement, feasibility, and readiness), but only 31% of the
sites formally started delivering the program to youth. Completing more pre
implementation activities, particularly those related to readiness, predicted
program start-up. Qualitative analysis comparing those that implemented the
program to those that did not revealed critical differences in decision-making
processes, leadership strategies, and the presence of local champions for the
program. This study documented the patterns of clinic behavior that occurs as
part of large-scale training efforts, suggests some unique challenges that occur
in schools, and highlights the importance of engaging in particular
implementation activities (i.e., readiness planning, stakeholder consensus and
planning meetings) as part of program start-up. Findings indicate that pre
implementation and readiness-related consultation should be employed as part of
broad-scale implementation and training efforts.
PMID- 29937255
TI - A Method for Tracking Implementation Strategies: An Exemplar Implementing
Measurement-Based Care in Community Behavioral Health Clinics.
AB - Implementation experts suggest tailoring strategies to the intended context may
enhance outcomes. However, it remains unclear which strategies are best suited to
address specific barriers to implementation, in part because few measurement
methods exist that adhere to recommendations for reporting. In the context of a
dynamic cluster randomized trial comparing a standardized to tailored approach to
implementing measurement-based care (MBC), this study aimed to (a) describe a
method for tracking implementation strategies, (b) demonstrate the method by
tracking strategies generated by teams tasked with implementing MBC at their
clinics in the tailored condition, and (c) conduct preliminary examinations of
the relation between strategy use and implementation outcomes (i.e., self
reported fidelity to MBC). The method consisted of a coding form based on
Proctor, Powell, and McMillen (2013) implementation strategy reporting guidelines
and Powell et al.'s (2012) taxonomy to facilitate specification of the
strategies. A trained research specialist coded digitally recorded implementation
team meetings. The method allowed for the following characterization of strategy
use. Each site generated 39 unique strategies across an average of six meetings
in five months. There was little variability in the use of types of
implementation strategies across sites with the following order of prevalence:
quality management (50.00%), restructuring (16.53%), communication (15.68%),
education (8.90%), planning (7.20%), and financing (1.69%). We identified a new
category of strategies not captured by the existing taxonomy, labeled
"communication." There was no evidence that number of implementation strategies
enacted was statistically significantly associated with changes in self-reported
fidelity to MBC-however, financing strategies were associated with increased
fidelity. This method has the capacity to yield rich data that will inform
investigations into tailored implementation approaches.
PMID- 29937256
TI - Group CBT for Externalizing Disorders in Urban Schools: Effect of Training
Strategy on Treatment Fidelity and Child Outcomes.
AB - Public schools are an ideal setting for the delivery of mental health services to
children. Unfortunately, services provided in schools, and more so in urban
schools, have been found to lead to little or no significant clinical
improvements. Studies with urban school children seldom report on the effects of
clinician training on treatment fidelity and child outcomes. This study examines
the differential effects of two levels of school-based counselor training:
training workshop with basic consultation (C) vs. training workshop plus enhanced
consultation (C+) on treatment fidelity and child outcomes. Fourteen school staff
members (counselors) were randomly assigned to C or C+. Counselors implemented a
group cognitive behavioral therapy protocol (Coping Power Program, CPP) for
children with or at risk for externalizing behavior disorders. Independent coders
coded each CPP session for content and process fidelity. Changes in outcomes from
pre to post were assessed via a parent psychiatric interview and interviewer
rated severity of illness and global impairment. Counselors in C+ delivered CPP
with significantly higher levels of content and process fidelity compared to
counselors in C. Both C and C+ resulted in significant improvement in interviewer
rated impairment; the conditions did not differ from each other with regard to
impairment. Groups did not differ with regard to pre- to- posttreatment changes
in diagnostic severity level. School-based behavioral health staff in urban
schools are able to implement interventions with fidelity and clinical
effectiveness when provided with ongoing consultation. Enhanced consultation
resulted in higher fidelity. Enhanced consultation did not result in better
student outcomes compared to basic consultation. Implications for resource
allocation decisions with staff training in EBP are discussed.
PMID- 29937257
TI - Economic Impact of the Statewide Implementation of an Evidence-Based Treatment:
Multisystemic Therapy in New Mexico.
AB - Several states have made considerable investments into large-scale implementation
of evidence-based treatments (EBTs), yet little is known about key success
indicators for these implementation efforts such as cost and sustainability. To
that end, the present study examined the economic impact of statewide
implementation of multisystemic therapy (MST; Henggeler, Schoenwald, Borduin,
Rowland, & Cuningham, 2009), a family- and community-based behavioral EBT for
serious juvenile offenders in New Mexico. Participants were 1,869 youth who
received MST across 23 teams during the study period. We conducted a cost-benefit
analysis using metrics from state data sources that compared the cost of MST to
its benefits (i.e., avoided expenses from pre- to posttreatment) in two domains:
(a) behavioral health services (i.e., Medicaid claims) and (b) juvenile crime
(i.e., taxpayer expenses, tangible and intangible expenses to crime victims). MST
costs were based on Medicaid claims, which were reimbursed at an enhanced billing
rate that was intended to cover expenses for both clinical and implementation
(e.g., training, quality assurance) activities. Results suggest that
implementation of MST in New Mexico over the 7-year study period may have
produced net benefits, through 2 years posttreatment, of more than $4,643 per
youth in avoided behavioral health claims and $15,019 per youth through
reductions in juvenile crime. Stated differently, every dollar that New Mexico
spent on MST appeared to have returned $3.34 for a total benefit of $64.2 million
over the course of the study. We discuss implications of these findings for
policymakers, administrators, and researchers who are interested in increasing
the sustainability of complex EBTs in community settings.
PMID- 29937259
TI - Predictive Relationship Between Parental Beliefs and Accommodation of Pediatric
Anxiety.
AB - Behavior performed by parents to assist a youth in avoiding or alleviating
anxiety, known as accommodation, is ubiquitous among pediatric anxiety disorders
and strongly related to poor treatment outcome. According to cognitive-behavioral
theory, the beliefs parents hold regarding accommodation should predict parental
accommodating behavior. Unfortunately, little is known about the beliefs parents
hold regarding accommodation, as there exists no validated measure of this
construct. First, the psychometric properties were examined for the Parental
Accommodation Scale (PAS), a novel measure of parental accommodating behavior
frequency (PAS-Behavior scale) and parental beliefs about accommodation (PAS
Belief scale). Second, the relationship between parental beliefs about
accommodation and accommodation frequency was examined. Results provide
preliminary evidence of the internal consistency and convergent validity of the
PAS. Stronger positive beliefs about accommodation significantly predicted
accommodation frequency, even after controlling for youth anxiety severity.
Specifically, beliefs that accommodation prevents youth from losing behavioral
and emotional control significantly predicted accommodation frequency. Therefore,
efforts to decrease accommodation in clinical settings should involve correcting
maladaptive parental beliefs about accommodation, with a particular emphasis on
beliefs regarding the necessity of accommodation in preventing a youth from
losing behavioral and emotional control.
PMID- 29937258
TI - Improved Parent Cognitions Relate to Immediate and Follow-Up Treatment Outcomes
for Children With ADHD-Predominantly Inattentive Presentation.
AB - We investigated treatment effects on parenting self-efficacy and parent cognitive
errors, and whether these parent cognitions are related to short- and long-term
outcomes in parenting behaviors in psychosocial treatment for youth with
attention-deficit/hyperactivity disorder, predominantly inattentive presentation
(ADHD-I). In a randomized controlled trial across two sites (University of
California, San Francisco, and University of California, Berkeley), 199 children
between the ages of 7 and 11 were randomized to the Child Life and Attention
Skills (CLAS; n = 74) program, parent-focused treatment (PFT; n = 74), or
treatment as usual (TAU; n = 51). Parents reported on self-efficacy, cognitive
errors, positive parenting, and negative parenting prior to treatment,
immediately after treatment, and in the next school year at follow-up. Compared
to TAU, CLAS and PFT had higher posttreatment parenting self-efficacy, and CLAS
alone had lower posttreatment parent cognitive errors. At follow-up, only CLAS
had improved parent cognitive errors compared to TAU. No other between-group
differences were found in parenting self-efficacy or cognitive errors. Improved
parenting self-efficacy was associated with improved posttreatment negative
parenting outcomes for PFT and CLAS, and improved parent cognitive errors were
also related to improvements in positive and negative posttreatment parenting
outcomes for CLAS. Posttreatment parenting self-efficacy mediated follow-up
negative parenting outcomes for CLAS and posttreatment parent cognitive errors
mediated improved follow-up positive and negative parenting outcomes for CLAS.
PFT and CLAS led to enhanced parenting self-efficacy, and CLAS appears especially
robust in improving parent cognitive errors both in the short and long term.
Pathways provide support for the possibility of parent cognitions as mediators of
treatment effects on parenting; clinical focus on such cognitions may be useful.
PMID- 29937260
TI - Have Phobias, Will Travel: Addressing One Barrier to the Delivery of an Evidence
Based Treatment.
AB - Although a host of evidence-based treatments exist for youth with anxiety
disorders, less than 30% of youth and their families receive these treatments.
One of the main barriers to receiving these treatments is the lack of access to
care, due largely to the absence of mental health professionals who have
expertise in the delivery of these treatments in certain geographic locales. The
current study examined whether a brief intensive treatment for specific phobias
(SPs), Augmented One-Session Treatment (OST-A), would result in comparable
treatment gains for families who traveled a considerable distance to receive this
treatment when compared to families who resided in our local community.
Participants included 76 youth with a clinically confirmed diagnosis of SP (38
local families and an age- and sex-matched sample of 38 nonlocal families).
Although SP severity at pretreatment was significantly greater for the nonlocal
youth than the local youth, both nonlocal and local youth showed commensurate
improvement and maintenance of treatment gains over a 6-month period across
several clinical outcome measures. Findings from this study show that OST-A is
effective when families choose to travel for treatment, addressing at least one
of the barriers to use of this evidence-based treatment.
PMID- 29937261
TI - Emotion Regulation of Events Central to Identity and Their Relationship With
Concurrent and Prospective Depressive Symptoms.
AB - Dispositional emotion regulation is related to the severity and maintenance of
depressive symptoms. However, whether emotion regulation specific to an event
highly central for an individual's identity is predictive of depressive symptoms
has not been examined. Nonclinical participants (N = 220) reported the extent to
which they employed a selection of emotion regulation strategies when recalling
low- and high-centrality events. Dispositional emotion regulation and depressive
symptoms were also assessed. A 7-week follow-up was conducted. High-centrality
events were associated with more emotion regulation efforts. Greater brooding and
expressive suppression in relation to high-centrality memories predicted
concurrent depressive symptoms after controlling for event valence and
dispostional emotion regulation. Effects were absent for low-centrality memories.
Emotion regulation in response to high-centrality memories did not predict
depressive symptoms at follow-up beyond baseline depressive symptoms. Overall,
the findings showed that maladaptive emotion regulation in response to memories
of high-centrality events is important for explaining depressive symptomatology.
PMID- 29937262
TI - Does Traumatic Brain Injury Attenuate the Exposure Therapy Process?
AB - Research indicates that exposure therapy is efficacious for combat-related
posttraumatic stress disorder (PTSD) comorbid with traumatic brain injury (TBI)
as is shown by reduced PTSD treatment outcome scores. What is unknown, however,
is whether the process of fear extinction is attenuated in veterans with TBI
history. Increased PTSD symptomatology and possible cognitive deficits associated
with TBI sequelae may indicate additional or longer exposure sessions to achieve
habituation and extinction comparable to individuals without TBI history. As
such, a more extensive course of treatment may be necessary to achieve comparable
PTSD treatment outcome scores for individuals with TBI history. Using a sample of
veterans with combat-related PTSD, some of whom were comorbid for TBI, this study
compared process variables considered relevant to successful treatment outcome in
exposure therapy. Individuals with and without TBI demonstrated similar rates of
fear activation, length and number of exposure sessions, within-session
habituation, between-session habituation, and extinction rate; results remained
consistent when controlling for differential PTSD symptomatology. Furthermore,
results indicated that self-perception of executive dysfunction did not impact
the exposure process. Results suggest that individuals with PTSD and TBI history
engage successfully and no differently in the exposure therapy process as
compared to individuals with PTSD alone. Findings further support exposure
therapy as a first-line treatment for combat-related PTSD regardless of TBI
history.
PMID- 29937263
TI - Acceptability, Feasibility, and Effectiveness of Internet-Based Cognitive
Behavioral Therapy for Obsessive-Compulsive Disorder in New York.
AB - Cognitive-behavioral therapy (CBT), consisting of exposure and response
prevention (EX/RP), is both efficacious and preferred by patients with obsessive
compulsive disorder (OCD), yet few receive this treatment in practice. This study
describes the implementation of an Internet-based CBT program (ICBT) developed in
Sweden in individuals seeking OCD treatment in New York. After translating and
adapting the Swedish ICBT for OCD, we conducted an open trial with 40 adults with
OCD. Using the RE-AIM implementation science framework, we assessed the
acceptability, feasibility, and effectiveness of ICBT. The Yale-Brown Obsessive
Compulsive Scale (Y-BOCS) was the primary outcome measure. Of 40 enrolled, 28
participants completed the 10-week ICBT. In the intent-to-treat sample (N = 40),
Y-BOCS scores decreased significantly over time (F = 28.12, df = 2, 49, p < .
001). Depressive severity (F = 5.87, df = 2, 48, p < . 001), and quality of life
(F = 12.34, df = 2, 48, p < . 001) also improved. Sensitivity analyses among
treatment completers (N = 28) confirmed the intent-to-treat results, with a large
effect size for Y-BOCS change (Cohen's d = 1.38). ICBT took less time to
implement than face-to face EX/RP and participants were very to mostly satisfied
with ICBT. On a par with results in Sweden, the adapted ICBT program reduced OCD
and depressive symptoms and improved quality of life among individuals with
moderate to severe OCD. Given its acceptability and feasibility, ICBT deserves
further study as a way to increase access to CBT for OCD in the United States.
PMID- 29937264
TI - Ammonia determines transcriptional profile of microorganisms in anaerobic
digestion.
AB - Anaerobic digestion is important for the management of livestock manure with high
ammonia level. Although ammonia effects on anaerobic digestion have been
comprehensively studied, the molecular mechanism underlying ammonia inhibition
still remains elusive. In this study, based on metatranscriptomic analysis, the
transcriptional profile of microbial community in anaerobic digestion under low
(1500mgL-1) and high NH4+ (5000mgL-1) concentrations, respectively, were
revealed. The results showed that high NH4+ concentrations significantly
inhibited methane production but facilitated the accumulations of volatile fatty
acids. The expression of methanogenic pathway was significantly inhibited by high
NH4+ concentration but most of the other pathways were not significantly
affected. Furthermore, the expressions of methanogenic genes which encode acetyl
CoA decarbonylase and methyl-coenzyme M reductase were significantly inhibited by
high NH4+ concentration. The inhibition of the co-expressions of the genes which
encode acetyl-CoA decarbonylase was observed. Some genes involved in the pathways
of aminoacyl-tRNA biosynthesis and ribosome were highly expressed under high NH4+
concentration. Consequently, the ammonia inhibition on anaerobic digestion mainly
focused on methanogenic process by suppressing the expressions of genes which
encode acetyl-CoA decarbonylase and methyl-coenzyme M reductase. This study
improved the accuracy and depth of understanding ammonia inhibition on anaerobic
digestion.
PMID- 29937265
TI - The effectiveness of lying surfaces in nursing care beds, a comparison of spring
element systems versus conventional systems: A post marketing clinical follow-up
pilot study.
AB - BACKGROUND: Reduced mobility is a strong risk factor for pressure ulcer
development in a nursing home setting. Despite this, there is a surprising lack
of data regarding suitable nursing care beds in general and the prevention of
pressure ulcers provided by lying surface systems in particular. In this context
we aimed to assess the mobility of patients using lying surface systems either
with spring elements (SES) and to compare these to conventional systems (CS;
wooden slats or steel bars). METHODS: This was a prospective, randomized,
controlled study in 29 patients with an age range of 54-95 years. Patients were
randomly assigned to SES (n = 15) or CS (n = 14). The primary objective was to
show a statistically significant difference in the proportion of patients with
normal (up to 4 movements per hour) movements as evaluated by the Mobility
Monitor(r). Pressure distribution of the lying body weight was measured by a full
body pressure mapping system XSensor(r). Comfort, possibility of movement and
recovery of sleep as well as pain at rest were self-rated. RESULTS: We screened a
total of 39 patients of which 29 were eligible to be randomized into the two
groups and 27 were finally analysed (SES = 14; CS = 13). The mean age was 81.7 +/
9.5 years, 81.5% were female and the mean Braden Scale Score 22.4 +/- 1.3. We
observed no statistically significant difference in the primary evaluation
criterion (proportion of patients with a normal number of movements across 14
nights) between the SES group (81.4 +/- 10.8%) and the CS group (72.9 +/- 16.3%;
p = 0.0757). There was a consistent trend for more movements in the normal range
in the SES group however, which was observed when the number of hours with normal
movement was plotted per night (p = 0.0004). Measured pressure values showed
overall higher values for the lateral compared to the dorsal position with the
SES but not the CS forming a "shoulder" between 35-55 mmHg in the dorsal position
and between 35-45 mmHg in the lateral position. Self-rated comfort was
significantly higher with the SES after night 14 (p = 0.0192) than with CS.
CONCLUSIONS: The study is not aimed at the hard endpoint pressure ulcer, but at
the physiological movement profile of patients in bed, which justifies a much
smaller number of cases. For elderly nursing home patients it appears that beds
with spring elements may be associated with higher normality of body movements
and higher self-rated comfort. The presented study could be a contribution to
reduce the care dependency of patients regarding mobility.
PMID- 29937266
TI - What is special about the human arcuate fasciculus? Lateralization, projections,
and expansion.
AB - Evolutionary adaptations of the human brain are the basis for our unique
abilities such as language. An expansion of the arcuate fasciculus (AF), the
dorsal language tract, in the human lineage involving left lateralization is
considered canonical, but this hypothesis has not been tested in relation to
other architectural adaptations in the human brain. Using diffusion-weighted MRI,
we examined AF in the human and macaque and quantified species differences in
white matter architecture and surface representations. To compare surface results
in the two species, we transformed macaque representations to human space using a
landmark-based monkey-to-human cortical expansion model. We found that the human
dorsal AF, but not the ventral inferior fronto-occipital fasciculus (IFO), is
left-lateralized. In the monkey AF is not lateralized. Moreover, compared to the
macaque, human AF is relatively increased with respect to IFO. A comparison of
human and transformed macaque surface representations suggests that cortical
expansion alone cannot account for the species differences in the surface
representation of AF. Our results show that the human AF has undergone critical
anatomical modifications in comparison with the macaque AF. More generally, this
work demonstrates that studies on the human brain specializations underlying the
language connectome can benefit from current methodological advances in
comparative neuroanatomy.
PMID- 29937267
TI - Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS
Program randomised clinical trials.
AB - BACKGROUND: In the Canagliflozin Cardiovascular Assessment Study (CANVAS)
Program, canagliflozin reduced the rates of major adverse cardiovascular events
and the results suggested a renal benefit in patients with type 2 diabetes who
were at high risk for cardiovascular events, compared with those treated with
placebo. Here we report the results of a prespecified exploratory analysis of the
long-term effects of canagliflozin on a range of sustained and adjudicated renal
outcomes. METHODS: The CANVAS Program consists of two double-blind, randomised
trials that assessed canagliflozin versus placebo in participants with type 2
diabetes who were at high risk of cardiovascular events, done at 667 centres in
30 countries. People with type 2 diabetes and an HbA1c of 7.0-10.5% (53-91
mmol/mol) who were aged at least 30 years and had a history of symptomatic
atherosclerotic vascular disease, or who were aged at least 50 years and had at
least two cardiovascular risk factors were eligible to participate. Participants
in CANVAS were randomly assigned (1:1:1) to receive 300 mg canagliflozin, 100 mg
canagliflozin, or matching placebo once daily. Participants in CANVAS-R were
randomly assigned (1:1) to receive canagliflozin or matching placebo, at an
initial dose of 100 mg daily, with optional uptitration to 300 mg from week 13 or
matching placebo. Participants and all study staff were masked to treatment
allocations until study completion. Prespecified outcomes reported here include a
composite of sustained and adjudicated doubling in serum creatinine, end-stage
kidney disease, or death from renal causes; the individual components of this
composite outcome; annual reductions in estimated glomerular filtration rate
(eGFR); and changes in urinary albumin-to-creatinine ratio (UACR). The trials are
registered with ClinicalTrials.gov, numbers NCT01032629 (CANVAS) and NCT01989754
(CANVAS-R). FINDINGS: Between Nov 17, 2009, and March 7, 2011 (CANVAS), and Jan
17, 2014, and May 29, 2015 (CANVAS-R), 15 494 people were screened, of whom 10
142 participants (with a baseline mean eGFR 76.5 mL/min per 1.73 m2, median UACR
12.3 mg/g, and 80% of whom were receiving renin-angiotensin system blockade) were
randomly allocated to receive either canagliflozin or placebo. The composite
outcome of sustained doubling of serum creatinine, end-stage kidney disease, and
death from renal causes occurred less frequently in the canagliflozin group
compared with the placebo group (1.5 per 1000 patient-years in the canagliflozin
group vs 2.8 per 1000 patient-years in the placebo group; hazard ratio 0.53, 95%
CI 0.33-0.84), with consistent findings across prespecified patient subgroups.
Annual eGFR decline was slower (slope difference between groups 1.2 mL/min per
1.73 m2 per year, 95% CI 1.0-1.4) and mean UACR was 18% lower (95% CI 16-20) in
participants treated with canagliflozin than in those treated with placebo. Total
serious renal-related adverse events were similar between the canagliflozin and
placebo groups (2.5 vs 3.3 per 1000 patient-years; HR 0.76, 95% CI 0.49-1.19).
INTERPRETATION: In a prespecified exploratory analysis, canagliflozin treatment
was associated with a reduced risk of sustained loss of kidney function,
attenuated eGFR decline, and a reduction in albuminuria, which supports a
possible renoprotective effect of this drug in people with type 2 diabetes.
FUNDING: Janssen Research & Development.
PMID- 29937268
TI - Renal outcomes in CVOTs: keep calm and carry on.
PMID- 29937269
TI - Assessment of daily activity patterns and biomarkers of pain, inflammation, and
stress in lactating dairy cows diagnosed with clinical metritis.
AB - The objectives of the present case-control study were to assess (1) daily
activity patterns (lying time, number of steps, number of lying bouts, and lying
bout duration), and (2) circulating concentrations of biomarkers of pain
(substance P), inflammation (haptoglobin), and stress (cortisol) in lactating
dairy cows diagnosed with clinical metritis. Lactating dairy cows (n = 200) from
2 commercial dairy herds were enrolled in the present study. Cows diagnosed with
clinical metritis (n = 100) at 7 +/- 3 d in milk were matched according to
lactation and days in milk to cows without clinical metritis (NO-CM; n = 100). On
study d 1, clinical metritis was diagnosed (using a Metricheck device, Simcro
Tech Ltd., Hamilton, New Zealand) by the presence of watery, reddish, or brownish
foul-smelling vaginal discharge, and blood samples were collected for assessment
of circulating concentration of substance P, haptoglobin, cortisol, total
calcium, beta-hydroxybutyrate, and blood cells. In addition, on study d 1 body
condition of cows was visually assessed, and activity monitors were placed on the
hind leg of a subset of cows (CM, n = 56; CON, n = 56) and were kept until study
d 7. Cows showing any other signs of other diseases were not included in the
study. Cows with clinical metritis tended to spend more time lying (CM = 628.92
min/d; NO-CM = 591.23 min/d) compared with NO-CM cows. Activity analysis by
parity revealed that primiparous cows with clinical metritis spent more time
lying compared with primiparous cows without clinical metritis. However, no
differences in daily lying time were observed between multiparous cows with and
without clinical metritis. Furthermore, cows in the CM group had a higher
circulating concentration of substance P (CM = 47.15 pg/mL; NO-CM = 37.73 pg/mL)
and haptoglobin (CM = 233.00 ug/mL; NO-CM = 99.98 ug/mL) when compared with NO-CM
cows. Cows with clinical metritis had lower body condition score, and a greater
proportion of cows in this group had hypocalcemia when compared with cows without
clinical metritis. The circulating concentration of leukocytes and erythrocytes
were decreased in cows with clinical metritis compared with cows without clinical
metritis. Results from this study showed that concentrations of markers of
inflammation, stress, pain, and activity were affected in cows diagnosed with
clinical metritis; thus, strategies aimed to minimize the negative effects
associated with clinical metritis may be required to improve the welfare of dairy
cows.
PMID- 29937270
TI - In-vivo analysis of sliding distance and cross-shear in Bi-cruciate retaining
total knee arthroplasty.
AB - Polyethylene remains the most popular bearing material for total knee
arthroplasty (TKA). Despite its widespread use, wear continue to be one of major
factors implicated in revision surgery. Sliding distance, cross-shear, and
contact stress are the major factors influencing polyethylene wear. As previous
studies have either relied on wear simulations, computational modeling, or in
vitro measurements to quantify sliding distance and cross-shear, in vivo subject
specific sliding distance and cross-shear after bi-cruciate retaining (BCR) TKA
has not been previously reported. The objective of this study was to quantify the
6 degrees -of-freedom (6DOF) in vivo kinematics, sliding distance, and cross
shear in BCR TKA patients during gait. Twenty-nine unilateral BCR TKA patients
performed level walking on a treadmill under dual fluoroscopic imaging system
(DFIS) surveillance. Cumulative normalized sliding distances between the lateral
and medial compartments did not change significantly (p > 0.05) during the gait
cycle. Although the total normalized sliding distance was similar between the
lateral and medial compartments, the cross-shear at the lateral compartment
differed significantly from that at the medial compartment (p < 0.001).
Significant differences in the relative length positions of the peak sliding
distance and cross-shear were found between the lateral and medial bearing
components. The flexion-extension motion of the reconstructed knee was more
associated with the linear displacements (anterior-posterior, R2 = 0.6; lateral
medial, R2 = 0.8, proximal-distal, R2 = 0.7) than the angular displacement (varus
valgus, R2 = 0.18; internal-external rotation, R2 = 0.28). Despite some
differences in peak sliding distance and cross-shear positons, our results
suggest similar articular contact patterns between the lateral and medial
compartments in BCR TKA patients during gait. The data could provide insights
into understanding the potential wear patterns in BCR TKAs.
PMID- 29937271
TI - Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of cGAS to Mediate Immune
Evasion.
AB - The cytosolic DNA sensor cGAS recognizes viral DNA and synthesizes the second
messenger cGAMP upon viral infection. cGAMP binds to the adaptor protein
MITA/STING to activate downstream signaling events, leading to induction of type
I interferons (IFNs) and antiviral effector genes. Here we identify the human
cytomegalovirus (HCMV) protein UL31 as an inhibitor of cGAS. UL31 interacts
directly with cGAS and disassociates DNA from cGAS, thus inhibiting cGAS
enzymatic functions and reducing cGAMP production. UL31 overexpression markedly
reduces antiviral responses stimulated by cytosolic DNA, while knockdown or
knockout of UL31 heightens HCMV-triggered induction of type I IFNs and downstream
antiviral genes. Moreover, wild-type HCMV replicates more efficiently than UL31
deficient HCMV, a phenotype that is reversed in cGAS null cells. These results
highlight the importance of cGAS in the host response to HCMV as well as an
important viral strategy to evade this innate immune sensor.
PMID- 29937273
TI - Cost-effectiveness and Budget Impact of Treatment with Evolocumab Versus Statins
and Ezetimibe for Hypercholesterolemia in Spain.
AB - INTRODUCTION AND OBJECTIVES: To analyze the cost-effectiveness ratio and budget
impact of treatment with evolocumab (PCSK9 inhibitor) for patients in secondary
prevention in the Spanish National Health System. METHODS: A budget impact
analysis, decision tree and Markov models were designed under the public health
system perspective, based on the only study with morbidity and mortality data
(FOURIER). The alternatives compared were evolocumab vs statins, and dual therapy
with ezetimibe in 5% of the population. The measure of effectiveness used was the
number of cardiovascular events avoided. Univariate and probabilistic sensitivity
analyses were performed. RESULTS: The average annual cost of patients receiving
evolocumab was 11 134.78? and 393.83? for standard treatment (statins plus
ezetimibe). The incremental cost-effectiveness ratio was > 600 000 ? per avoided
cardiovascular event for both assessed outcomes (first: cardiovascular death,
myocardial infarction, stroke, and hospitalization due to unstable angina or
coronary revascularization; second: includes the first 3 events). To perform the
10-year Markov model, the average cost of standard treatment was 13 948.45? vs
471 417.37? with evolocumab. Treatment with evolocumab for patients with familial
hypercholesterolemia would cost between 3 and 6.1 million euros, assuming a
difference of 2.5 and 5.1 million euros with the standard treatment (2017). This
difference would be between 204.3 and 1364.7 million euros (2021) for those with
nonfamiliar hypercholesterolemia (secondary prevention). CONCLUSIONS: Treatment
with evolocumab is associated with a lower frequency of cardiovascular events,
but is inefficient for patients suitable to receive this drug in the Spanish
National Health System.
PMID- 29937274
TI - Next day discharge rate has little use as a quality measure for individual
physician performance.
AB - INTRODUCTION: Emergency Department (ED) physicians' next day discharge rate
(NDDR), the percentage of patients who were admitted from the ED and subsequently
discharged within the next calendar day was hypothesized as a potential measure
for unnecessary admissions. The objective was to determine if NDDR has validity
as a measure for quality of individual ED physician performance. METHODS:
Hospital admission data was obtained for thirty-six ED physicians for calendar
year 2015. Funnel plots were used to identify NDDR outliers beyond 95% control
limits. A mixed model logistic regression was built to investigate factors
contributing to NDDR. To determine yearly variation, data from calendar years
2014 and 2016 were analyzed, again by funnel plots and logistic regression.
Intraclass correlation coefficient was used to estimate the percent of total
variation in NDDR attributable to individual ED physicians. RESULTS: NDDR varied
significantly among ED physicians. Individual ED physician outliers in NDDR
varied year to year. Individual ED physician contribution to NDDR variation was
minimal, accounting for 1%. Years of experience in Emergency Medicine practice
was not correlated with NDDR. CONCLUSION: NDDR does not appear to be a reliable
independent quality measure for individual ED physician performance. The percent
of variance attributable to the ED physician was 1%.
PMID- 29937272
TI - Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial
Sepsis.
AB - Sepsis is a life-threatening condition caused by pathogen infection and
associated with pyroptosis. Pyroptosis occurs upon activation of proinflammatory
caspases and their subsequent cleavage of gasdermin D (GSDMD), resulting in GSDMD
N-terminal fragments that form membrane pores to induce cell lysis. Here, we show
that antioxidant defense enzyme glutathione peroxidase 4 (GPX4) and its ability
to decrease lipid peroxidation, negatively regulate macrophage pyroptosis, and
septic lethality in mice. Conditional Gpx4 knockout in myeloid lineage cells
increases lipid peroxidation-dependent caspase-11 activation and GSDMD cleavage.
The resultant N-terminal GSDMD fragments then trigger macrophage pyroptotic cell
death in a phospholipase C gamma 1 (PLCG1)-dependent fashion. Administration of
the antioxidant vitamin E that reduces lipid peroxidation, chemical inhibition of
PLCG1, or genetic Caspase-11 deletion or Gsdmd inactivation prevents
polymicrobial sepsis in Gpx4-/- mice. Collectively, this study suggests that
lipid peroxidation drives GSDMD-mediated pyroptosis and hence constitutes a
potential therapeutic target for lethal infection.
PMID- 29937275
TI - Brain Somatic Mutations in MTOR Disrupt Neuronal Ciliogenesis, Leading to Focal
Cortical Dyslamination.
AB - Focal malformations of cortical development (FMCDs), including focal cortical
dysplasia (FCD) and hemimegalencephaly (HME), are major etiologies of pediatric
intractable epilepsies exhibiting cortical dyslamination. Brain somatic mutations
in MTOR have recently been identified as a major genetic cause of FMCDs. However,
the molecular mechanism by which these mutations lead to cortical dyslamination
remains poorly understood. Here, using patient tissue, genome-edited cells, and
mouse models with brain somatic mutations in MTOR, we discovered that disruption
of neuronal ciliogenesis by the mutations underlies cortical dyslamination in
FMCDs. We found that abnormal accumulation of OFD1 at centriolar satellites due
to perturbed autophagy was responsible for the defective neuronal ciliogenesis.
Additionally, we found that disrupted neuronal ciliogenesis accounted for
cortical dyslamination in FMCDs by compromising Wnt signals essential for
neuronal polarization. Altogether, this study describes a molecular mechanism by
which brain somatic mutations in MTOR contribute to the pathogenesis of cortical
dyslamination in FMCDs.
PMID- 29937276
TI - Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of
Molecular, Genetic, and Clinical Networks by Human Herpesvirus.
AB - Investigators have long suspected that pathogenic microbes might contribute to
the onset and progression of Alzheimer's disease (AD) although definitive
evidence has not been presented. Whether such findings represent a causal
contribution, or reflect opportunistic passengers of neurodegeneration, is also
difficult to resolve. We constructed multiscale networks of the late-onset AD
associated virome, integrating genomic, transcriptomic, proteomic, and
histopathological data across four brain regions from human post-mortem tissue.
We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV
7) from subjects with AD compared with controls. These results were replicated in
two additional, independent and geographically dispersed cohorts. We observed
regulatory relationships linking viral abundance and modulators of APP
metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and
PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and
neuropathological features with viral activity and is consistent with viral
activity constituting a general feature of AD.
PMID- 29937277
TI - Vascular Compartmentalization of Functional Hyperemia from the Synapse to the
Pia.
AB - Functional hyperemia, a regional increase of blood flow triggered by local neural
activation, is used to map brain activity in health and disease. However, the
spatial-temporal dynamics of functional hyperemia remain unclear. Two-photon
imaging of the entire vascular arbor in NG2-creERT2;GCaMP6f mice shows that local
synaptic activation, measured via oligodendrocyte precursor cell (OPC) Ca2+
signaling, generates a synchronous Ca2+ drop in pericytes and smooth muscle cells
(SMCs) enwrapping all upstream vessels feeding the activated synapses.
Surprisingly, the onset timing, direction, and amplitude of vessel diameter and
blood velocity changes vary dramatically from juxta-synaptic capillaries back to
the pial arteriole. These results establish a precise spatial-temporal sequence
of vascular changes triggered by neural activity and essential for the
interpretation of blood-flow-based imaging techniques such as BOLD-fMRI.
PMID- 29937278
TI - A Dynamic Bayesian Observer Model Reveals Origins of Bias in Visual Path
Integration.
AB - Path integration is a strategy by which animals track their position by
integrating their self-motion velocity. To identify the computational origins of
bias in visual path integration, we asked human subjects to navigate in a virtual
environment using optic flow and found that they generally traveled beyond the
goal location. Such a behavior could stem from leaky integration of unbiased self
motion velocity estimates or from a prior expectation favoring slower speeds that
causes velocity underestimation. Testing both alternatives using a probabilistic
framework that maximizes expected reward, we found that subjects' biases were
better explained by a slow-speed prior than imperfect integration. When subjects
integrate paths over long periods, this framework intriguingly predicts a
distance-dependent bias reversal due to buildup of uncertainty, which we also
confirmed experimentally. These results suggest that visual path integration in
noisy environments is limited largely by biases in processing optic flow rather
than by leaky integration.
PMID- 29937279
TI - Enhanced Neural Processing by Covert Attention only during Microsaccades Directed
toward the Attended Stimulus.
AB - Attention can be "covertly" directed without eye movements; yet, even during
fixation, there are continuous microsaccades (MSs). In areas V4 and IT of
macaques, we found that firing rates and stimulus representations were enhanced
by attention but only following a MS toward the attended stimulus. The onset of
neural attentional modulations was tightly coupled to the MS onset. The results
reveal a major link between the effects of covert attention on cortical visual
processing and the overt movement of the eyes.
PMID- 29937282
TI - Discussion.
PMID- 29937280
TI - Layer I Interneurons Sharpen Sensory Maps during Neonatal Development.
AB - The neonatal mammal faces an array of sensory stimuli when diverse neuronal types
have yet to form sensory maps. How these inputs interact with intrinsic neuronal
activity to facilitate circuit assembly is not well understood. By using
longitudinal calcium imaging in unanesthetized mouse pups, we show that layer I
(LI) interneurons, delineated by co-expression of the 5HT3a serotonin receptor
(5HT3aR) and reelin (Re), display spontaneous calcium transients with the highest
degree of synchrony among cell types present in the superficial barrel cortex at
postnatal day 6 (P6). 5HT3aR Re interneurons are activated by whisker stimulation
during this period, and sensory deprivation induces decorrelation of their
activity. Moreover, attenuation of thalamic inputs through knockdown of NMDA
receptors (NMDARs) in these interneurons results in expansion of whisker
responses, aberrant barrel map formation, and deficits in whisker-dependent
behavior. These results indicate that recruitment of specific interneuron types
during development is critical for adult somatosensory function. VIDEO ABSTRACT.
PMID- 29937281
TI - How Diverse Retinal Functions Arise from Feedback at the First Visual Synapse.
AB - Many brain regions contain local interneurons of distinct types. How does an
interneuron type contribute to the input-output transformations of a given brain
region? We addressed this question in the mouse retina by chemogenetically
perturbing horizontal cells, an interneuron type providing feedback at the first
visual synapse, while monitoring the light-driven spiking activity in thousands
of ganglion cells, the retinal output neurons. We uncovered six reversible
perturbation-induced effects in the response dynamics and response range of
ganglion cells. The effects were enhancing or suppressive, occurred in different
response epochs, and depended on the ganglion cell type. A computational model of
the retinal circuitry reproduced all perturbation-induced effects and led us to
assign specific functions to horizontal cells with respect to different ganglion
cell types. Our combined experimental and theoretical work reveals how a single
interneuron type can differentially shape the dynamical properties of distinct
output channels of a brain region.
PMID- 29937283
TI - Financial implications of coding inaccuracies in patients undergoing elective
endovascular abdominal aortic aneurysm repair.
AB - OBJECTIVE: Previous cost analyses have found small to negative margins between
hospitalization cost and reimbursement for endovascular aneurysm repair (EVAR).
Hospitals obtain reimbursement on the basis of Medicare Severity Diagnosis
Related Group (MS-DRG) coding to distinguish patient encounters with or without
major comorbidity or complication (MCC). This study's objective was to evaluate
coding accuracy and its effect on hospital cost for patients undergoing EVAR.
METHODS: A retrospective, single university hospital review of all elective,
infrarenal EVARs performed from 2010 to 2015 was completed. Index procedure
hospitalizations were reviewed for MS-DRG classification, comorbidities,
complications, length of stay (LOS), and hospitalization cost. Patients'
comorbidities and postoperative complications were tabulated to verify accuracy
of MS-DRG classification. Misclassified patients were audited and reclassified as
"standard" or "complex" on the basis of a corrected MS-DRG: standard for 238
(major cardiovascular procedure without MCC) and complex for 237 (major
cardiovascular procedure with MCC). RESULTS: There were 104 EVARs identified,
including 91 standard (original MS-DRG 238, n = 85; MS-DRG 254, n = 6) and 13
complex hospitalizations (original MS-DRG 237, n = 9; MS-DRG 238, n = 3; MS-DRG
253, n = 1). On review, 3% (n = 3) of the originally assigned MS-DRG 238 patients
were undercoded while actually meeting MCC criteria for a 237 designation.
Hospitalizations coded with MS-DRG 253 and 254 were considered billing errors
because MS-DRG 237 and 238 are more appropriate and specific classifications as
major cardiovascular procedures. Overall, there was a 9.6% miscoding rate (n =
10), representing a total lost billing opportunity of $587,799. Mean LOS for
standard and complex hospitalizations was 3.0 +/- 1.5 days vs 7.8 +/- 6.0 days (P
< .001), with respective intensive care unit LOS of 0.4 +/- 0.7 day vs 2.6 +/-
3.1 days (P < .001). Postoperative complications occurred in 23% of patients;
however, not all met the Centers for Medicare and Medicaid Services criteria as
MCC. Miscoded complexity was found to be due to postoperative events in all
patients rather than to missed comorbidities. Mean hospitalization cost for
standard and complex patients was $28,833 +/- $5597 vs $41,543 +/- $12,943 (P <
.001). Based on institutional reimbursement data, this translates to a mean loss
of $5407 per correctly coded patient. Miscoded patients represent an additional
overall reimbursement loss of $140,102. CONCLUSIONS: Our study reveals a large
lost billing opportunity with miscoding of elective EVARs from 2010 to 2015, with
errors in categorization of the procedure as well as miscoding of complexity. The
revenue impact is potentially significant in this population, and additional
reviews of coding practices should be considered.
PMID- 29937284
TI - Management of failed endovascular aortic aneurysm repair with explantation or
fenestrated-branched endovascular aortic aneurysm repair.
AB - OBJECTIVE: The incidence of failed endovascular aneurysm repair (EVAR) is
increasing, and understanding the different methods of management and repair is
paramount. The objective of this study was to evaluate the clinical management
and rescue of failed EVAR by either explantation or fenestrated-branched EVAR
(F/B-EVAR). METHODS: A retrospective analysis (1999-2016) of 247 patients who
underwent either explantation (n = 162) or F/B-EVAR (n = 85) for failed EVAR was
performed. F/B-EVAR was performed under a physician-sponsored investigational
device exemption. Demographics of the patients, clinical presentation and failure
etiology, perioperative management, rate of reinterventions, morbidity, and
mortality were analyzed. Those undergoing surgical explantation were compared
with those undergoing F/B-EVAR conversion. Statistical analysis included
multivariable logistic regressions, Fisher exact test, and chi2 test. RESULTS:
The majority of patients were male (n = 216 [87%]), with a mean age of 75 years
(range, 50-93 years). The mean time from primary EVAR was higher in F/B-EVAR (46
+/- 7 months vs 69 +/- 41 months; P < .001). Graft manufacturer did not differ
between those requiring explantation and those having endovascular rescue (P =
.170). All emergencies (n = 24 [10%]) and infections (n = 28 [11%]) were treated
with open conversion. Endoleak was the most common reason for failure in both
explantation and F/B-EVAR groups (75% vs 64%, respectively; P = .052). Type I
endoleak was the most common endoleak reported in both groups, occurring more
frequently in F/B-EVAR (64% vs 40%; P < .001); type II endoleak was more common
in those undergoing open repair (28% vs 2%; P < .001). Graft migration (12% vs
26%; P = .005) and neck degeneration/disease progression (14% vs 59%; P < .001)
were more prevalent in F/B-EVAR, but aneurysm enlargement was more common in
explantation (68% vs 33%; P < .001). Thirty-day reintervention rates did not
differ between F/B-EVAR and explantation (odds ratio, 0.6258; 95% confidence
interval, 0.2-1.86; P = .4115); however, 30-day mortality was lower in the F/B
EVAR group (5% vs 10%; P = .0192). Similarly, aneurysm-related mortality was also
lower in the F/B-EVAR group (hazard ratio, 0.0683; 95% confidence interval, 0.01
0.44; P = .0048). A subset analysis excluding emergencies and infections did not
alter the lack of difference in terms of freedom from reinterventions (P =
.1175), 30-day mortality (P = .6329), or aneurysm-related mortality (P = .7849).
CONCLUSIONS: Explantation and F/B-EVAR are necessary options in treating patients
with failed EVAR, and both techniques have competitive results. Different modes
of failure may point to a preferred method of treatment; consequently, rescue of
failed EVAR should be individualized according to each patient's presentation and
resources available.
PMID- 29937285
TI - Surgical internal iliac artery preservation associated with endovascular repair
of infrarenal aortoiliac aneurysms to avoid buttock claudication and distal type
I endoleaks.
AB - OBJECTIVE: The objective of this study was to assess outcomes of a hybrid
technique for treatment of abdominal aortic aneurysm (AAA) associated with iliac
aneurysm without distal neck by combining an AAA endovascular repair approach
with open surgery for preservation of the internal iliac artery (IIA). METHODS:
The files of 51 patients operated on between 1998 and 2017 in a single vascular
surgery department were retrospectively analyzed. Inclusion criteria were
patients with AAA associated with uni-iliac or bi-iliac aneurysm without suitable
distal sealing zone. Surgery consisted of deployment of an aortouni-iliac stent
graft combined with an extra-anatomic crossover prosthetic bypass. With use of a
limited retroperitoneal approach, the contralateral proximal common iliac
aneurysm was surgically excluded and the IIA revascularized by direct ilioiliac
anastomosis or terminal common iliac suture, preserving the iliac bifurcation.
RESULTS: The patients' mean age was 74 years (58-88 years), and 92% were men. The
mean follow-up was 5.8 years (0.1-18 years). Twenty-nine patients (57%) had one
or more high-risk criteria for open surgery. Nineteen patients (37.3%) had
aortouni-iliac aneurysms, 19 (37.3%) aortobi-iliac aneurysms, 5 (10%) isolated
iliac aneurysms, and 8 (15.7%) bi-iliac aneurysms without aortic location. Four
patients (7.8%) also had IIA aneurysms. Surgery was successful in all cases. Two
patients (4%) died during the 30 days after surgery. One surgically preserved IIA
occluded within the first month, resulting in buttock claudication. The 5-year
IIA primary patency rate was 96%. Type I proximal endoleaks occurred in two
patients, requiring additional surgery 3 years and 13 years after the initial
surgery, respectively. CONCLUSIONS: This hybrid technique, consisting of AAA
endovascular exclusion combined with open IIA revascularization, is safe and
effective for preservation of pelvic vascularization. It is associated with long
term patency and low morbidity rates. We have been using this technique since
before the advent of branched dedicated devices, allowing preservation of the IIA
with good results. This technique should continue to be proposed, especially in
patients not eligible for endovascular iliac branch repair because of anatomic
contraindications, to avoid pelvic ischemia if the IIA has to be sacrificed.
PMID- 29937286
TI - Another means to meet MIPs requirements: The virtual group.
PMID- 29937287
TI - Peripheral atherectomy practice patterns in the United States from the Vascular
Quality Initiative.
AB - OBJECTIVE: Peripheral atherectomy has been shown to have technical success in
single-arm studies, but clinical advantages over angioplasty and stenting have
not been demonstrated, leaving its role unclear. We sought to describe patterns
of atherectomy use in a real-world U.S. cohort to understand how it is currently
being applied. METHODS: The Vascular Quality Initiative was queried to identify
all patients who underwent peripheral vascular intervention from January 2010 to
September 2016. Descriptive statistics were performed to analyze demographics of
the patients, comorbidities, indication, treatment modalities, and lesion
characteristics. The intermittent claudication (IC) and critical limb ischemia
(CLI) cohorts were analyzed separately. RESULTS: Of 85,605 limbs treated,
treatment indication was IC in 51% (n = 43,506) and CLI in 49% (n = 42,099).
Atherectomy was used in 15% (n = 13,092) of cases, equivalently for IC (15%; n =
6674) and CLI (15%; n = 6418). There was regional variation in use of
atherectomy, ranging from a low of 0% in one region to a high of 32% in another
region. During the study period, there was a significant increase in the
proportion of cases that used atherectomy (11% in 2010 vs 18% in 2016; P <
.0001). Compared with nonatherectomy cases, those with atherectomy use had higher
incidence of prior peripheral vascular intervention (IC, 55% vs 43% [P < .0001];
CLI, 47% vs 41% [P < .0001]), greater mean number of arteries treated (IC, 1.8 vs
1.6 [P < .0001]; CLI, 2.1 vs 1.7 [P < .0001]), and lower proportion of prior leg
bypass (IC, 10% vs 14% [P < .0001]; CLI, 11% vs 17% [P < .0001]). There was lower
incidence of failure to cross the lesion (IC, 1% vs 4% [P < .0001]; CLI, 4% vs 7%
[P < .0001]) but higher incidence of distal embolization (IC, 1.9% vs 0.8% [P <
.0001]; CLI, 3.0% vs 1.4% [P < .0001]) and, in the CLI cohort, arterial
perforation (1.4% vs 1.0%; P = .01). CONCLUSIONS: Despite a lack of evidence for
atherectomy over angioplasty and stenting, its use has increased across the
United States from 2010 to 2016. It is applied equally to IC and CLI populations,
with no identifiable pattern of comorbidities or lesion characteristics,
suggesting that indications are not clearly delineated or agreed on. This study
places impetus on further understanding of the optimal role for atherectomy and
its long-term clinical benefit in the management of peripheral arterial disease.
PMID- 29937288
TI - Discussion.
PMID- 29937289
TI - Lower extremity bypass and endovascular intervention for critical limb ischemia
fail to meet Society for Vascular Surgery's objective performance goals for limb
related outcomes in a contemporary national cohort.
AB - OBJECTIVE: In 2009, the Society for Vascular Surgery (SVS) developed objective
performance goals (OPGs) to define the therapeutic benchmarks in critical limb
ischemia (CLI) based on outcomes from randomized trials of lower extremity bypass
(LEB). Current performance relative to these benchmarks in both LEB and
infrainguinal endovascular intervention (IEI) remains unknown. The objective of
this study was to determine whether LEB and IEI performed for CLI in a
contemporary national cohort met OPG 30-day safety thresholds. METHODS: SVS OPG
criteria were applied to 11,043 revascularizations for CLI performed from 2011 to
2015 in the National Surgical Quality Improvement Program (NSQIP) vascular
targeted modules. Primary 30-day safety OPGs including major adverse
cardiovascular events (MACEs), major adverse limb events (MALEs), and amputation
were calculated for the NSQIP LEB (n = 3833) and IEI (n = 3526) cohorts as well
as for subgroups at "high anatomic risk" (infrapopliteal revascularization) and
"high clinical risk" (age >80 years and tissue loss). These were compared with
SVS OPG benchmarks using chi2 comparisons. RESULTS: Compared with the SVS OPG
cohort, both the NSQIP LEB and IEI cohorts had fewer patients at high anatomic
risk (LEB, 51%; IEI, 27%; SVS OPG, 60%; both P < .0001). The LEB cohort had fewer
patients with high clinical risk than the SVS OPG cohort (LEB, 11%; SVS OPG, 16%;
P < .0001). The 30-day MALE was significantly higher in the NSQIP LEB (9.0% [8.7%
9.2%]) and IEI (9.7% [9.4%-10.0%]) cohorts compared with the SVS OPG cohort (6.1%
[4.7%-9.0%]; both P <= .007), including significantly higher rates of amputation.
MACE was significantly lower in the NSQIP LEB (4.2% [4.1%-4.3%]) and IEI (3.1%
[3.0%-3.2%]) cohorts compared with the SVS OPG cohort (6.1% [4.7%-8.1%]; both P
<= .013). Among patients at high anatomic risk, 30-day MALE was significantly
higher after LEB (9.5% [9.1%-9.8%]) and IEI (11.1% [10.4-11.8%]) compared with
the SVS OPG cohort (6.1% [4.2%-8.6%]; P <= .002). Among patients with high
clinical risk, IEI was associated with lower MACE compared with the SVS OPG
cohort, with similar limb-related outcomes. CONCLUSIONS: In contemporary real
world practice, LEB and IEI for CLI failed to meet SVS OPG limb-related 30-day
safety benchmarks for the entire CLI cohort as well as for the patients at high
anatomic risk. Additional investigation using SVS OPGs as consistent end points
is required to determine why limb-related outcomes after revascularization for
CLI remain suboptimal. LEB and IEI surpassed OPG benchmarks for 30-day
cardiovascular morbidity and mortality. OPGs for cardiovascular morbidity in
patients undergoing revascularization for CLI deserve re-evaluation using
contemporary data.
PMID- 29937290
TI - Choice of a second vascular access in hemodialysis patients whose initial
arteriovenous fistula failed to mature.
AB - OBJECTIVE: We have previously shown that arteriovenous fistulas (AVFs) are more
expensive to create and to maintain than arteriovenous grafts (AVGs) in patients
undergoing their first access. Because those for whom this first access fails may
be a more disadvantaged group, we hypothesized that the cost of a second access
may be different from that in the primary access group. With this in mind, we
compared access costs in patients receiving a secondary AVF or AVG after their
initial AVF failed to mature. METHODS: This was a retrospective cohort study of
92 patients who received a second vascular access (44 AVFs and 48 AVGs) after
their first AVF failed to mature. We quantified the yearly frequency of
percutaneous or surgical access interventions and catheter-related bacteremias
(CRBs) using a computerized vascular access database. The costs associated with
access procedures were quantified using the outpatient prospective payment
schedule, and those related to hospitalization for CRB were determined from the
diagnosis-related groups fee schedule. RESULTS: Patients receiving an AVF had
fewer percutaneous procedures than those receiving an AVG (2.09 [95% confidence
interval, 1.86-2.34] vs 2.61 [2.35-2.88]; P = .004), tended to undergo surgical
interventions more frequently (1.21 [1.04-1.40] vs 1.00 [0.84-1.17]; P = .08),
and experienced a similar yearly frequency of CRB hospitalizations (0.40 [0.31
0.52 vs 0.28 [0.20-0.38]; P = .07). Patients with a secondary AVF vs an AVG had a
similar median yearly cost of percutaneous access interventions ($3567
[interquartile range, $1219-$4680] vs $4989 [$1570-$9752]; P = .14) and surgical
access procedures ($6403 [$3494-$13,127] vs $4728 [$2563-$12,254]; P = .38) but a
higher annual cost for CRBs ($3405 [$0-$12,825] vs $0 [$0-$5477]; P = .04). The
total yearly access-related cost was similar in both groups ($19,477 [$9162
$36,916] vs $18,285 [$6850-$31,768]; P = .56). CONCLUSIONS: Patients undergoing a
secondary AVF required more surgical procedures and sustained more bacteremia
complications than patients undergoing a secondary AVG implantation. There was no
significant difference in the total cost of access care for hemodialysis patients
receiving a secondary AVF vs AVG.
PMID- 29937292
TI - Qualitative Research Process Applied to Organ Donation.
AB - The family interview for organ donation continues to be one of the main concerns
of transplant coordinators. We approach the family because we need to know the
opinion of the person who has just died about the donation of his or her organs.
The objective of this article is to describe how the application of the
qualitative methodology has been followed to perceive what the relatives live in
the moment in which they are informed of the death of their relative and they are
offered the option of organ donation. Phenomenology is a philosophy that deals
with the granting of meanings. It can simply describe or try to interpret them.
Our informants were selected from among donor families until the 11 families were
obtained. We use the Giorgi method because it allows us to identify the essence
of a phenomenon and transform the lived experience into a textual expression of
its essence. The unit of analysis was, each of the statements of the discourse
that describes and interprets a reality, what we call "essence" or "meaning
units." It must be the minimum expression of an episode and the experience in
relation to it. We have detected 24 themes of the meaning units are most
important for families in our area. Families agree on talking about donation,
mourning, death, consolation from the donation, and the importance of the support
received. Phenomenology is adequate to deepen into the feelings and interests of
families in the process of donation.
PMID- 29937291
TI - Obesity Risk Factors in Patients After Kidney Transplantation.
AB - BACKGROUND: Kidney transplantation is currently the best approach for renal
replacement therapy. Compared with dialysis, it provides a better quality of life
and improves patient prognosis. However, some evidence suggests that body
composition could play a role in the complications observed in kidney transplant
recipients (KTRs), and may influence survival. The purpose of this study was to
assess the eating habits and body composition of KTRs. METHODS: Seventy KTRs were
included in this study. Anthropometry and body composition were performed using
electronic-scale, dynamometer, and bioimpedance analyses. Dietary habits were
investigated using the Food Frequency Questionnaire (FFQ6). Biochemical
parameters were also determined. RESULTS: Overweight and obesity were found in
33.8% and 21.1% of KTRs, respectively. High body mass index (BMI, >25) correlated
positively with high body fat (r = 0.8, P < .05) and waist circumference (r =
0.7, P < .05). The mean percentage of body fat was 30.8 +/- 9.3% (range, 13%
52%), fat tissue index was 12.4 +/- 4.9, and lean tissue index (LTI) was 13.2 +/-
2.2. Sarcopenia was recognized based on decreased LTI and decreased handgrip
strength in 33.3% of KTRs with excess body weight. Patients with excess body mass
consumed significantly (P < .05) more sugar and fruits. CONCLUSION: A significant
percentage of KTRs present with sarcopenic obesity. Excess body weight is
associated with many factors, such as immunosuppressive therapy, low physical
activity, and abnormal diet. Results based on the FFQ6 indicate a relationship
between carbohydrate intake and excess body weight among those in the study
group.
PMID- 29937293
TI - Attitude and Knowledge of Medical Students of Tabriz University of Medical
Sciences Regarding Organ Donation.
AB - BACKGROUND: The shortage of organ donation is the key rate-limiting factor for
organ transplantation in Iran. Many strategies have been proposed to increase
donation; one strategy aims to improve awareness of organ donation and
transplantation among medical students. Medical students may play an important
role in the acceptance of organ donation in the population. This requires both a
positive attitude and an appropriate knowledge about the concept of organ
donation and transplantation. The objective of this study was to determine the
knowledge and attitude of the medical students of the largest medical university
in northwestern Iran. METHODS: Four hundred medical students in the 5th and 6th
years of their education were enrolled in this study. They completed a self
administered 3-section questionnaire. Section 1 gathered demographic
characteristics, section 2 covered attitude, and section 3 assessed knowledge
regarding organ donation. RESULTS: The concept of brain death and criteria
involved in organ transplant was understood by 57% of the students. Most of the
students thought that there is a need to increase awareness regarding brain death
and organ donation transplantation (ODT). Eighty-five percent of the students
said that they would donate their organs, but 15% did not, most likely because of
religion and body disfigurement. Seventy-eight percent of students would donate
their organs to their family, relatives, or friends. Sixty-four percent thought
that the family can decide regarding ODT. Seventy percent were willing to donate
the organs of their family members after brain death. Religion and source of
information regarding ODT has a significant effect on knowledge and attitude of
students. CONCLUSIONS: Students had a high level of attitude, but a low level of
basic understanding about organ donation that lacked detailed knowledge. They
accept its importance and desire further teaching to supplement their current
knowledge to be able to understand the issues related to organ donation. The
results of this study supported a greater emphasis on revising the curricula in
medical schools to improve the knowledge of future health care workers. This
strategy may be part of the solution to the chronic shortage of donor organs for
transplantation.
PMID- 29937295
TI - Optimization of biolayer interferometer-based binding assay of the interaction
between the Candida albicans protein Pra1 and complement protein C3.
PMID- 29937294
TI - The Importance of New Generation Sequencing (NGS) HLA Typing in Renal
Transplantation-Preliminary Report.
AB - INTRODUCTION: Thanks to new generation sequencing (NGS) and expansion of HLA
typing with additional loci, it will be possible to increase the effectiveness of
graft survival and to avoid complications related to the immune system. New
pharmacogenetic factors are still being researched to develop better
immunosuppressive treatment. MATERIAL AND METHODS: The incidence of polymorphic
HLA loci variants was established, based on a high-resolution NGS method in
kidney graft recipients. Furthermore, haplotypic analysis between examined loci
was conducted to type additional loci that may influence the transplantation
result. A total of 120 kidney recipients were enrolled in the study. A commercial
DNA extraction kit in Tubes (QIAamp DNA Blood Mini Kit Qiagen, Germany) was used
to isolate DNA from the blood. Sequencing library preparation was done with
TruSight HLA set. The Conexio computer program was used to analyse the results of
HLA typing. RESULTS: The patients with alleles A*02:01:01, B*44:02:01,
C*03:03:01, C*01:02:01, C*05:01:01, C*07:02:01, DQB1*03:03:02, DQB1*06:04:01, or
with haplotypic variation A*25:01:01-B*18:01:01- C*15:01:01 were taking the
highest doses of cyclosporine (CsA), in contrast to patients with allele
B*18:01:01, DQB1*06:02:01, DQB1*02:02:01, or haplotypic variation A*02:01:01-
B*44:02:01-C*01:01:01, who were taking the lowest doses. The highest dose of
tacrolimus (TAC) was administered to patients with alleles A*68:01:02,
A*29:01:01, B*07:02:01, B*35:02:01, B*38:01:01, DRB1*12:01:01, DQB1*05:03:01, or
haplotypic variations A*02:01:01-B*57:01:01-C*07:01:01, A*03:01:01-B*07:02:01
C*13:01:01, A*29:02:01-B*44:03:01- C*07:01:01, and A*01:01:01-B*08:01:01
C*03:01:01. Additionally, it was established that HLA-DRB3, HLA-DRB4, HLA-DRB5,
HLA-DPA1, and HLA-DQA1 show very slight polymorphism, which suggests that there
is no need for their typing for transplantation purposes. Moreover, loci HLA-C,
HLA-DQB1, and HLA-DPB1, which are not routinely examined in recipient-donor
matching, show genetic variability that may increase the risk of transplant
rejection or shortened graft life. CONCLUSIONS: Expanding the qualification
procedure to include allele genotyping could allow clinicians to establish
immunosuppressive treatment schemes that would be optimally suited for
recipients' phenotype.
PMID- 29937297
TI - Laparoscopic approach in complete cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy by CO2 closed system in a low grade pseudomyxoma
peritonei.
PMID- 29937296
TI - Postoperative complications and survival rate of esophageal cancer: Two-period
analysis.
AB - INTRODUCTION: Nowadays, treatment of esophageal cancer requires a
multidisciplinary approach, in which esophagectomy remains the mainstay. The aim
of this report is to assess whether multimodal treatment and minimally invasive
surgery have led to a lower morbidity rate and an improvement in survival rates.
METHODS: Retrospective evaluation of 318 patients diagnosed with esophageal
cancer including 81 esophagectomies. The periods of 2000-2007 and 2008-2015 were
compared, analyzing the prognostic factors that may have an impact in morbidity
and survival rate. RESULTS: Major postoperative complications according to the
Clavien-Dindo classification accounted for 35%, showing a decrease between the
1.st and 2.nd period: 41% morbidity vs. 30%, 27% mortality vs. 9% (p < .001) and
13.5% fistulas vs. 7%. The implementation of thoracoscopic esophagectomy
contributed to the outcome improvement, as shown by 19% morbidity and 5%
mortality rates, with triangularized mechanical anastomosis showing 9% fistula
and 5% stenosis. The overall 5-year survival rate was 19%, with a significant
increase from 11% in the 1.st period to 28% in the 2.nd (p < .001). CONCLUSIONS:
Multidisciplinary assessment of patients with esophageal cancer, as well as
better selection and indication of treatment and the introduction of new
minimally invasive techniques (thoracoscopy and triangularized mechanical
anastomosis), have improved the morbidity and mortality rates of esophagectomies,
resulting in increased survival rates of these patients.
PMID- 29937298
TI - [Chronic intestinal pseudo-obstruction in adults].
AB - Chronic intestinal pseudo-obstruction is a rare disease stemming from numerous
causes characterized by disturbances in gastrointestinal motility. Symptomatology
is often misleading and topography is variable, thus putting the clinician in
serious difficulty. Diagnosis is based on a body of arguments, ranging from the
clinical examination to surgical biopsies in expert centers. Treatment is non
consensual and mostly symptomatic. It is based on the use of prokinetics and
optimal nutritional support. In the most serious cases, surgery can be required.
The etiological treatment should be that of the causal disease when it exists and
when the etiology is identified. Results of such treatment are variable. Chronic
intestinal pseudo-obstruction is a disease which remains poorly understood.
Progress had been made in terms of diagnosis and treatment but it seems obvious
that a better comprehension of physiopathological mechanisms is necessary in
order to improve our practice.
PMID- 29937299
TI - [How to minimize the risk of infection in systemic lupus erythematosus?]
PMID- 29937300
TI - Safety of FFR-guided revascularisation deferral in Anatomically prognostiC
diseasE (FACE: CARDIOGROUP V STUDY): A prospective multicentre study.
AB - BACKGROUND: FFR-guided coronary intervention is recommended for patients with
intermediate stenoses. However, concerns exist with this approach in anatomically
prognostic disease. METHODS: In this prospective, multicentre study, we
consecutively enrolled patients found to have FFR negative lesions in
anatomically significant sites: left main; proximal LAD; last remaining patent
vessel; and multiple vessels with concomitant impaired left ventricular systolic
function (EF < 40%). As per recommendation, revascularisation was deferred, and
patients included into a registry. The primary endpoint was MACE (death,
myocardial infarction and unplanned target lesion revascularization). Secondary
endpoints were the above individual components. Subgroup analyses were performed
for clinical presentation (stable vs. ACS), localization of lesion (ostial vs.
non ostial) and renal function. RESULTS: The registry included 292 patients with
297 deferred stenoses. After 1-year, the primary endpoint occurred in 5% of
patients, mainly driven by TLR (2.7%). Cardiovascular death occurred in 0.8% and
AMI in 0.8%. During a follow-up of 22.2 +/- 11 months, MACE occurred in 11.6%.
Cardiovascular death occurred in 1.8% and AMI in 2.1%. After multivariate
analysis, impaired renal function (OR 1.99; CI 95% 1.74-5.41; p = 0.046) and
ostial disease (OR 2.88; CI 95% 1.04-7.38; p = 0.041) were found to be predictors
of MACE. Impaired renal function also predicted TLR (OR 2.43; CI 95% 1.17-5.02; p
= 0.017). CONCLUSION: FFR-guided revascularisation deferral is safe in the
majority of anatomically prognostic disease. However, further evaluation is
required in the risk stratification of those patients with ostial disease and
renal disease. Registered on ClinicalTrials, NCT02590926.
PMID- 29937301
TI - Definitions of peri-procedural myocardial infarction and the association with one
year mortality: Insights from CHAMPION trials.
AB - BACKGROUND: Controversies exist over the appropriate definition for peri
procedural myocardial infarction (PPMI) and its association with mortality. This
study aims to evaluate one-year survival following percutaneous coronary
intervention (PCI) and the association of different definitions of PPMI with
survival among patients with stable angina (SA) or acute coronary syndrome (ACS)
in the contemporary era. METHODS: We used data from the CHAMPION PLATFORM and
CHAMPION PCI trials of patients undergoing PCI and conducted univariable and
multivariable Cox proportional hazard regression models to evaluate mortality
risk during the first year after PCI. A blinded events committee adjudicated
suspected PPMI defined by biomarker elevations >=3* the upper limit of normal
(ULN) or new Q-waves. We further analyzed PPMI by the magnitude of CK-MB
elevation ([a] 3 to <5* ULN, [b] 5 to <10* ULN, [c] >=10* ULN) or by the 2nd
universal definition of myocardial infarction (UDMICK-MB) excluding patients with
evidence of myocardial infarction (MI) prior to PCI. RESULTS: Of 13,968 patients,
11% initially presented with SA, and 89% with ACS. One-year mortality was 3.4%
(SA: 1.5%; ACS: 3.6%). PPMI occurred in 6.3% of the patients (3 to <5* ULN: 2.5%;
5 to <10* ULN: 2.1%; >=10* ULN: 1.6%; UDMICK-MB: 2.7%). After multivariable
adjustment, a significantly higher risk of one-year mortality was observed for
patients with PPMI compared with patients without PPMI (HR 2.35 [1.74-3.18], p <
0.001; 3 to <5* ULN: 1.55 [0.92-2.62], p = 0.10; 5 to <10* ULN: 1.22 [0.67-2.20],
p = 0.52; >=10* ULN: 4.78 [3.06-7.47], p < 0.001; UDMICK-MB: 2.19 [1.29-3.73], p
= 0.004). CONCLUSION: PPMI occurred in 6.3% of the patients and was associated
with increased risk of death within one year. Survival was not significantly
impacted by PPMI if defined by periprocedural CK-MB elevations <10* ULN alone and
without additional evaluation of symptoms or evidence of ischemia. These findings
highlight the importance of PPMI for long-term outcome in the contemporary era
and of its definition in the planning and interpretation of clinical trials.
PMID- 29937303
TI - [Is the vertical transmission of Chlamydia trachomatis a little known problem in
Spain?]
PMID- 29937302
TI - Molecular imaging of inflammation in atherosclerosis of the carotid arteries.
PMID- 29937304
TI - [Sudden death due to undiagnosed congenital diaphragmatic hernia].
PMID- 29937305
TI - [Pyosalpinx In A Prepubescent Girl With Hirschsprung's Disease].
PMID- 29937306
TI - Young child as a donor of cells for transplantation and lymphocyte based
therapies.
AB - In most cases of hematopoietic cell transplantation (HSCT) in pediatric
recipient, the priority is given to bone marrow as a hematopoietic cell (HSC)
source. The same expectations should be given to pediatric sibling donor. Bone
marrow (BM) harvest is a standard method of HSC collection in pediatric siblings,
however peripheral blood HSC (PBSC) collection is safe in healthy pediatric
donors, and target hematopoietic cell yields can be achieved. Bone marrow or
peripheral blood cell collection, both hematopoietic cells and lymphocytes, in
pediatric sibling donors is safe, however there is a small risk of severe adverse
events (SAE); still the risk of SAE is lower in children than in adults. The
early adverse effects (AE) both after BM and PBSC collection are mild, short-term
and easy to prevent or control, however they can occur in a relatively large
proportion of donors. The risk of mild AE is lower in children than in adults,
except PBSC collection in children <20 kg, who might be at risk of various
complications. Short-term G-CSF administration and PBSC collection in pediatric
donors is safe. No data exist on long-term adverse effects of short-term G-CSF
course. Pediatric donors and their parents must be informed about the risk of
possible complications.
PMID- 29937307
TI - Metagenomics Sheds Light on the Ecology of Marine Microbes and Their Viruses.
AB - Advances brought about by omics-based approaches have revolutionized our
understanding of the diversity and ecological processes involving marine archaea,
bacteria, and their viruses. This broad review discusses recent examples of how
genomics, metagenomics, and ecogenomics have been applied to reveal the ecology
of these biological entities. Three major topics are covered in this revision:
(i) the novel roles of microorganisms in ecosystem processes; (ii) virus-host
associations; and (iii) ecological associations of microeukaryotes and other
microbes. We also briefly comment on the discovery of novel taxa from marine
ecosystems; development of a robust taxonomic framework for prokaryotes;
breakthroughs on the diversity and ecology of cyanobacteria; and advances on
ecological modelling. We conclude by discussing limitations of the field and
suggesting directions for future research.
PMID- 29937308
TI - Disparate genomic characteristics of concurrent endometrial adenocarcinoma and
ovarian granulosa cell tumor, revealed by targeted next-generation sequencing.
AB - Concurrence of both endometrial adenocarcinoma and ovarian adult granulosa cell
tumor (aGCT) is believed to be related to high estrogen milieu, but genomic
alterations of the concurrent endometrial adenocarcinoma and aGCT are not known.
For this, we analyzed an uterine endometrial adenocarcinoma and an ovarian aGCT
in a same patient by a targeted next generation sequencing (NGS). We found a
germline mutation in STK11 (p.L113fs). The endometrial adenocarcinoma harbored
FGFR2 and TP53 mutations and the aGCT harbored a FOXL2 (p.C134 W) mutation. These
germline and somatic mutations have been reported in non-concurrent tumors. These
two tumors harbored 20 CNAs but only one CNA was exactly overlapped in the
tumors. Our findings indicate that the concurrent endometrial adenocarcinoma and
aGCT in this patient might not be genetically related to each other at germline
or somatic level and suggest that such concurrence might be originated from non
genetic backgrounds including stimulated estrogen milieu.
PMID- 29937309
TI - The possible association between the presence of an MPO -463 G > A (rs2333227)
polymorphism and cervical cancer risk.
AB - PURPOSE: The association between myeloperoxidase (MPO) polymorphism and the risk
of cervical cancer is inconclusive. We performed a meta-analysis to clarify if a
correlation exists between MPO polymorphism and the risk for developing cervical
cancer. METHODS: All case-control research studies that determined a relationship
between MPO and cervical cancer reported up until March 1, 2018 in PubMed, Web of
Science, VIP, WanFang, and the CNKI Database were accessed and included. The
strength of association was evaluated with pooled odds ratios (ORs) and their
corresponding 95% confidence intervals (95% CIs). We used sensitivity analysis to
detect the stability of our results, conducted Q-test to evaluate heterogeneity
and applied Begg's funnel plot and Egger's test to investigate any publication
bias among selected studies. RESULTS: In this meta-analysis, we included 5
eligible studies in the final evaluation, which included 1125 patients with
cervical cancer and 1150 cancer-free control patients. A potential association
between the MPO -463 G > A polymorphism and cervical cancer risk was observed
(recessive model: OR = 0.65, 95%, CI: 0.43-0.98, P = 0.038; homozygous model: OR
= 0.65, 95%, CI: 0.43-0.99, P = 0.045), which indicates that genotype AA reduces
the risk of cervical cancer by 35% compared to GG/GA or GG genotypes in our
results. A stratified analysis by ethnicity identified a significant correlation
among Caucasian patients (recessive model: OR = 0.57, 95%, CI: 0.34-0.95, P =
0.029; homozygous model: OR = 0.60, 95%, CI: 0.36-0.99, P = 0.048) and a
stratified analysis by source of control identified a significant correlation
among population-based studies. CONCLUSIONS: Our results suggest that the
presence of polymorphism, -463 G > A in patients might offer them protection
against cervical cancer. By implementing randomized case-control or cohort
studies with larger sample sizes, the clinical significance of our results can be
further strengthened and verified.
PMID- 29937310
TI - Influence of a gel emulsion containing microalgal oil and a blackthorn (Prunus
spinosa L.) branch extract on the antioxidant capacity and acceptability of
reduced-fat beef patties.
AB - The addition of a blackthorn branch extract (Prunus spinosa L.) to a gel emulsion
system containing microalgal oil was examined in order to obtain a functional
ingredient (APG), for use as fat replacer in beef patties. Chromatographic
analysis indicated that catechins were the major polyphenols present in the
Prunus spinosa L. extract. The antioxidant capacity increased as a result of the
extract addition, as shown by the comparison of the gel emulsions, with and
without it (APG and AG, respectively). Beef patties containing APG as fat
replacer (modified patties) had a lower fat content (5.3% versus 10.75%), doubled
the antioxidant activity and the DHA content, and improved the stability against
oxidation by reducing the peroxide content more than two fold when compared to
control patties. In addition, instrumental color measured by the CIE L*a*b*
system showed no significant difference between control and modified raw patties.
Moreover, the sensory acceptability of the new formulation was confirmed by a
like/dislike hedonic test.
PMID- 29937311
TI - On farm factors increasing dark cutting in pasture finished beef cattle.
AB - The on-farm factors increasing the incidence of dark cutting were studied in 3145
pasture raised cattle consigned in 66 lots. Animal, environmental and farm
management factors were recorded and pasture quantity, quality and mycotoxin
concentrations were measured. The relative risk of dark cutting decreased by 26%
in cattle grazing pastures with magnesium concentrations exceeding 0.24%. There
was a 50% increase in relative dark cutting risk of cattle drinking from dams
compared to drinking from troughs. Feeding supplements (hay/silage) in the last 7
days prior to slaughter reduced the relative risk of dark cutting by 25%. A high
prevalence of mycotoxins was detected in pastures across all farms. In this case
pasture ergot alkaloid concentrations above 600PPB increased the relative risk of
dark cutting by 45%, while the presence of FumonisinB1 increased risk by 58%. In
contrast the presence of 3acetyldeoxynivalenol reduced the relative dark cutting
risk by 37%. Sex also affected the incidence of dark cutting, with heifers less
likely to cut dark than steers by 47%.
PMID- 29937312
TI - [The influence of anxiety and depression on COPD exacerbations].
AB - INTRODUCTION: Exacerbations are common during the course of chronic obstructive
pulmonary disease (COPD) and contribute to its morbidity and mortality. COPD is
also associated with high prevalence of anxiety and depression. OBJECTIVES: A
systematic literature review of data on the association between anxiety and/or
depression and COPD exacerbations. DOCUMENTARY SOURCES: Medline search, for the
1980-2017 period, with the following keywords: "chronic obstructive pulmonary
disease" or "COPD" and "exacerbation" and "anxiety" or "depression"; limits:
"title/abstract"; the selected languages were English or French. RESULTS: Among
152 articles, 77 abstracts have been preselected for a dual reading and 30
studies have been finally selected. The prevalence of anxiety and depression
ranged from 6.7 to 58% and 5.5 to 51.5%, respectively. Among the 30 studies
included in this review, 19 (63.3%) revealed positive associations between
anxiety and/or depression and increased risk for exacerbations, although 11
(36.7%) failed to support such an association. The association between anxiety
and/or depression and an increased risk of COPD exacerbations was more frequently
observed in studies using an event-based definition (85.7%) than in those using a
symptom-based definition (14.3%). The main limitation of this review is the high
heterogeneity of the studies included. Another limitation is the low rate of
women included in this review (32.6%). CONCLUSION: Anxiety and/or depression are
associated with a greater risk for exacerbations to occur in COPD. However, a
high heterogeneity across the published studies makes it difficult to draw any
firm conclusions on the amplitude of this increased risk.
PMID- 29937313
TI - [Characteristics of non-pharmacological interventions in the elderly with COPD.
Smoking cessation, pulmonary rehabilitation, nutritional management and patient
education].
AB - Chronic obstructive pulmonary disease (COPD) is a respiratory disorder
responsible for a high mortality and disability. People older than 65 years are
more commonly affected than younger people and tend to present with more symptoms
and a greater level of disability. Non-pharmacological interventions play an
important role in the management of all patients with COPD and this is
particularly true in the elderly. Given the improvement in quality of life and
risk of hospitalization, smoking cessation should be promoted to patients of all
ages. Increased physical activity is associated with reduced respiratory
symptoms. Tests such as the "Short Physical Performance Battery" can be useful in
frailer older people with COPD, while walking tests such as the 6-minute walk
test are used as an assessment before pulmonary rehabilitation. Increased
physical activity should be combined with nutritional management. Screening for
undernutrition by questionnaire, body mass index and albumin quantification is
recommended in the elderly. In case of undernutrition, oral supplementation seems
to reduce the risk of re-admission. All these measures must be included in an
education program adapted to the elderly comorbidities (hearing loss,
isolation...).
PMID- 29937314
TI - [Occurrence of visible molds in French schools and nurseries].
AB - Children exposure to molds in the school and preschool environment is not well
described in France. A nationwide survey was performed in 2009-2011 in 310
schools and nurseries from France including two oversea territories, Reunion and
Martinique. It showed that 5 % of the audited rooms had visible molds, mainly on
the ceiling. These rooms belonged to 34 buildings (11 %). The multivariate
analysis shows that several factors are associated with visible molds in rooms:
the presence of textile wall covering, the location of the building in a suburban
area, the size of the building (less visible molds in large buildings), the
absence of a ventilation system with exhaust located in the room, and the absence
of double-glazed windows. The prevalence of visible molds is comparable to the
one observed in large European studies: 7 % of the 334 classrooms in the frame of
the SINPHONIE project and 11 % of the buildings in 193 elementary schools in the
HITEA study.
PMID- 29937315
TI - Durable response in a woman with recurrent low-grade endometrioid endometrial
cancer and a germline BRCA2 mutation treated with a PARP inhibitor.
AB - A 42-year-old woman with a germline BRCA2 mutation and recurrent low-grade
endometrioid endometrial adenocarcinoma experienced clinical and radiographic
response to the poly (ADP ribose) polymerase (PARP) inhibitor, olaparib.
Molecular and treatment factors are discussed.
PMID- 29937316
TI - Management of established pressure ulcer infections in spinal cord injury
patients.
AB - OBJECTIVES: Pressure ulcers are frequently observed in spinal cord injury (SCI)
patients. They can be life-threatening and are a major medico-economic burden.
Despite their frequency, their pathophysiology and optimal management are still
poorly understood. Most available data comes from non-comparative studies,
especially in terms of antimicrobial use. METHODS: We performed a critical review
of the literature and opinions of infectious disease specialists based in a
French expert center for this disease. We mainly focused on antimicrobial
treatments prescribed in this situation. RESULTS: These infections are usually
clinically diagnosed. Microbiological samples are not the gold standard for this
assessment. Furthermore, reliable microbiological identification is a major
challenge but should help select antimicrobial treatment. Imaging technique could
be helpful but cannot replace the physical examination. The choice of
antimicrobials must consider the potential ecological collateral damages in this
vulnerable population. Antimicrobial therapy should be as short as possible,
adapted to the microbiological identification, and must have suitable
bioavailability. CONCLUSION: Management of infected pressure ulcers is a major
concern in disabled patients already highly exposed to antimicrobial treatment
and multidrug-resistant organisms colonization. Extensive data is required.
PMID- 29937317
TI - Resistin is elevated in cystic fibrosis sputum and correlates negatively with
lung function.
AB - BACKGROUND: Resistin is an immunometabolic mediator that is elevated in several
inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the
recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are
major drivers of cystic fibrosis (CF) lung disease, in part due to the release of
human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to
tissue damage. Here we assessed the relationship of resistin to CF lung disease.
METHODS: Resistin levels were measured in plasma and sputum from three
retrospective CF cohorts spanning a wide range of disease. We also assessed the
ability of neutrophils to secrete resistin upon activation in vitro. Finally, we
constructed a multivariate model assessing the relationship between resistin
levels and lung function. RESULTS: Plasma resistin levels were only marginally
higher in CF than in healthy control subjects. By contrast, sputum resistin
levels were very high in CF, reaching 50-100 fold higher levels than in plasma.
Among CF patients, higher plasma resistin levels were associated with allergic
bronchopulmonary aspergillosis, and higher sputum resistin levels were associated
with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary
granules was concomitant with resistin secretion. Overall, sputum resistin levels
were negatively correlated with CF lung function, independently of other
variables (age, sex, and genotype). CONCLUSIONS: Our data establish relationships
between resistin levels in the plasma and sputum of CF patients that correlate
with disease status, and identify resistin as a novel mechanistic link between
neutrophilic inflammation and lung disease in CF.
PMID- 29937319
TI - The Insidious Number Two.
PMID- 29937320
TI - The Mythical Dual-Process Typology.
PMID- 29937318
TI - AGTR2 absence or antagonism prevents cystic fibrosis pulmonary manifestations.
AB - BACKGROUND: Pulmonary disease remains the primary cause of morbidity and
mortality for individuals with cystic fibrosis (CF). Variants at a locus on the X
chromosome containing the type 2 angiotensin II receptor gene (AGTR2) were
identified by a large GWAS as significantly associating with lung function in CF
patients. We hypothesized that manipulating the angiotensin-signaling pathway may
yield clinical benefit in CF. METHODS: Genetic subset analysis was conducted on a
local CF cohort to extend the GWAS findings. Next, we evaluated pulmonary
function in CF mice with a deleted AGTR2 gene, and in those who were given
subcutaneous injections of PD123,319, a selective AGTR2 antagonist for 12 weeks
beginning at weaning. RESULTS: The genetic subset analysis replicated the initial
GWAS identified association, and confirmed the association of this locus with
additional lung function parameters. Studies in genetically modified mice
established that absence of the AGTR2 gene normalized pulmonary function indices
in two independent CF mouse models. Further, we determined that pharmacologic
antagonism of AGTR2 improved overall pulmonary function in CF mice to near wild
type levels. CONCLUSIONS: These results identify that reduced AGTR2 signaling is
beneficial to CF lung function, and suggest the potential of manipulating the
angiotensin-signaling pathway for treatment and/or prevention of CF pulmonary
disease. Importantly, the beneficial effects were not CF gene mutation dependent,
and were able to be reproduced with pharmacologic antagonism. As there are
clinically approved drugs available to target the renin-angiotensin signaling
system, these findings may be quickly translated to human clinical trials.
PMID- 29937321
TI - Coexistence of syndrome of resistance to thyroid hormones and differentiated
thyroid cancer.
PMID- 29937322
TI - Outcomes of necrotic immature open-apex central incisors treated by MTA
apexification using poly(epsilon-caprolactone) fiber mesh as an apical barrier.
AB - BACKGROUND/PURPOSE: Although unset mineral trioxide aggregate (MTA) has some
cytotoxicity, MTA is still a biocompatible material suitable for doing
apexification. This study assessed the outcomes for 8 necrotic immature open-apex
permanent maxillary central incisors treated by MTA apexification using
poly(epsilon-caprolactone) fiber mesh (PCL-FM) as an apical barrier (so-called
PCL-FM/MTA apexification) to prevent extrusion of MTA materials into the
periapical tissues of open-apex teeth. METHODS: Eight necrotic immature open-apex
permanent maxillary central incisors with the open apices measuring 2.5 mm-3.5 mm
in diameter in 8 patients (6 boys and 2 girls; age range, 8-10 years) were first
cleaned using ultrasonic activated irrigation with 2.5% sodium hypochlorite
solution and then treated by PCL-FM/MTA apexification procedure. RESULTS: All the
8 permanent maxillary central incisors showed successful outcomes after PCL
FM/MTA apexification procedure. The mean duration for apical hard tissue barrier
formation of the 8 incisors was 6.8 +/- 0.5 weeks (range 6-7 weeks). The mean
increased root length was 1.8 +/- 0.7 mm (range 1-3 mm) at 7 weeks and 3.1 +/-
0.6 mm (range 2-4 mm) at 3 months. The mean increased dentinal wall thickness at
the most apical portion of the root was 1.3 +/- 0.5 mm (range 1-2 mm) at 7 weeks
and 2.4 +/- 0.6 mm (range 1.5-3 mm) at 3 months. None of the teeth treated by PCL
FM/MTA apexification showed tooth discoloration after a follow-up period of 3
months. CONCLUSION: PCL-FM/MTA apexification is an excellent technique for
treatment of necrotic immature open-apex permanent maxillary central incisors.
PMID- 29937323
TI - A propensity score-matched comparison of intracorporeal and extracorporeal
techniques for robotic-assisted right colectomy in an Enhanced Recovery Pathway.
AB - INTRODUCTION: There may be short-term outcomes advantages for the intracorporeal
approach to minimally invasive right colectomy. METHODS: This is a retrospective
propensity score-matched comparison of intracorporeal and extracorporeal
techniques for robotic-assisted right colectomy in an Enhanced Recovery
colorectal surgery service. RESULTS: 55 intracorporeal and 55 extracorporeal
cases were compared. Operative time was significantly longer (p < 0.001) and
incision length shorter in the intracorporeal group (p = 0.007). Outcomes
significantly favorable for the intracorporeal group included conversion-to-open
(p = 0.013), time to first flatus (p < 0.001), time to first bowel movement (p =
0.006), and dehydration (p = 0.03). There were more extraction site hernias in
the midline compared to off-midline locations, though this difference did not
reach statistical significance (p = 0.06). CONCLUSION: There are outcomes
advantages for the intracorporeal technique for robotic-assisted right colectomy
when compared to the extracorporeal approach for patients in an Enhanced Recovery
Pathway. Training efforts should continue to advocate the intracorporeal option.
PMID- 29937324
TI - Synoptic operative reporting for laparoscopic cholecystectomy and
pancreaticoduodenectomy: A multi institutional pilot study evaluating
completeness and surgeon perceptions.
AB - BACKGROUND: Synoptic operative reports (SOR) are more accurate than dictated
operative reports (DOR) in a few single institution experiences. We sought to
examine the completeness of SOR for laparoscopic cholecystectomy (LC) and
pancreaticoduodenectomy (PD) in a multi institutional pilot study. METHODS: Six
institutions participated in SOR submission via a web-based survey. One
institution collected DOR and case matched historical dictated operative reports
(HOR) for subset analysis. A checklist evaluated completeness of all reports. A
post-survey assessed participant opinions. RESULTS: 40 PD SORs were 98.5%
complete and 35 LC SORs were 99.7% complete. Single institution subset analysis
respective percent complete were: 11 PD SORs 99%, DORs 70% and HORs 74% and 14 LC
SORs 99.7%, DORs 76%, and HORs 75%. Post-survey results yielded 10 PD and 24 LC
responses. An overwhelming majority agreed that SOR were easy to use and would
prefer to use SOR compared to DOR. CONCLUSION: SOR are more complete than both
study associated DOR and HOR. The majority of surgeons indicated their preference
for SOR and their willingness to use them.
PMID- 29937325
TI - Electroencephalographic biomarkers as predictors of methylphenidate response in
attention-deficit/hyperactivity disorder.
AB - : EEG biomarkers have shown promise in predicting non-response to stimulant
medication in ADHD and could serve as translational biomarkers. This study aimed
to replicate and extend previous EEG biomarkers. The international Study to
Predict Optimized Treatment for ADHD (iSPOT-A), a multi-center, international,
prospective open-label trial, enrolled 336 children and adolescents with ADHD
(11.9 yrs; 245 males; prescribed methylphenidate) and 158 healthy children.
Treatment response was established after six weeks using the clinician rated ADHD
Rating Scale-IV. Theta/Beta ratio (TBR) and alpha peak frequency (APF) were
assessed at baseline as predictors for treatment outcome. No differences between
ADHD and controls were found for TBR and APF. 62% of the ADHD group was
classified as a responder. Responders did not differ from non-responders in age,
medication dosage, and baseline severity of ADHD symptoms. Male-adolescent non
responders exhibited a low frontal APF (Fz: R = 9.2 Hz vs. NR = 8.1 Hz; ES =
0.83), whereas no effects were found for TBR. A low APF in male adolescents was
associated with non-response to methylphenidate, replicating earlier work. Our
data suggest that the typical maturational EEG changes observed in ADHD
responders and controls are absent in non-responders to methylphenidate and these
typical changes start emerging in adolescence. CLINICAL TRIALS REGISTRATION:
www.clinicaltrials.gov; NCT00863499
(https://clinicaltrials.gov/ct2/show/NCT00863499).
PMID- 29937326
TI - Social aversive conditioning in youth at clinical high risk for psychosis and
with psychosis: An ERP study.
AB - BACKGROUND: Social cognition and emotion processing are compromised in
schizophrenia. Disruptions in these domains may also be present during the
psychosis-risk state. Aversive conditioning is an established translational
research paradigm to investigate affective reactivity and learning. Using an
aversive conditioning ERP paradigm with social cues, we examined whether
psychosis patients and at-risk youths differentially respond to aversively
conditioned faces. METHODS: Participants (ages 10-30) were enrolled into three
demographically-matched groups: clinical risk for psychosis (CR, n = 32),
psychosis (PS, n = 26), and healthy control (HC, n = 33). EEGs were recorded
during a delay aversive conditioning task in which three neutral faces were
paired with an aversive tone at 100%, 50% and 0% contingencies. Analysis focused
on group differences in ERP peaks representing visual processing (occipital
P120), emotional valence (frontal VPP), and directed attention (parietal
occipital P300), for dimensions of aversiveness (100% vs. 0%) and
unpredictability (50% vs. 100% + 0%). RESULTS: HC, but not CR or PS, showed
increased P300 amplitude to aversive vs. non-aversive conditioned stimuli. CR,
but not PS or HC, showed increased VPP amplitude to unpredictable vs. predictable
stimuli. CONCLUSIONS: PS and CR both fail to allocate appropriate salience to
social cues that are predictably aversive. CR, but not PS exhibit heightened
emotional reactivity to social cues that are of uncertain salience. Clinical risk
for schizophrenia may involve neural abnormalities distinct from both healthy and
fully-established disease states.
PMID- 29937327
TI - Combination therapy of electroconvulsive therapy and aripiprazole for dopamine
supersensitivity psychosis.
PMID- 29937328
TI - Reply to Mark C. Kendall's Letter to the Editor re: Marc A. Furrer, Adrian
Fellmann, Marc P. Schneider, George N. Thalmann, Fiona C. Burkhard, Patrick Y.
Wuethrich. Impact of Packed Red Blood Cells and Fresh Frozen Plasma Given During
Radical Cystectomy and Urinary Diversion on Cancer-related Outcome and Survival:
An Observational Cohort Study. Eur Urol Focus. In press.
https://doi.org/10.1016/j.euf.2017.09.010.
PMID- 29937329
TI - Hexvix plus Chemo.
AB - While photodynamic diagnosis during transurethral resection of bladder tumor
seems warranted only in seemingly high-risk cases, early intravesical
instillation of chemotherapy is warranted in all low-risk cases. According to the
latest randomized controlled trial, data may make sense also in intermediate- and
high-risk cases.
PMID- 29937330
TI - Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Penile Squamous Cell
Carcinoma Patients Undergoing Inguinal Lymph Node Dissection.
AB - BACKGROUND: Further biomarkers are warranted to improve prognostic stratification
of penile squamous cell carcinoma (PSCC) patients undergoing inguinal lymph node
dissection (ILND). OBJECTIVE: To assess the prognostic value of pretreatment
neutrophil-to-lymphocyte ratio (NLR) in PSCC patients undergoing ILND and to
investigate its role in predicting pathologic node-positive (pN+) disease.
DESIGN, SETTING, AND PARTICIPANTS: In total, 84 consecutive patients undergoing
ILND for PSCC at our institution between 1994 and 2014 were identified. Sixty
eight patients with a complete blood count and differential prior to surgery were
included. Median follow-up was 35.5 mo. OUTCOMES MEASUREMENTS AND STATISTICAL
ANALYSIS: Cut-off point analysis of NLR was performed using the Contal and
O'Quigley method. Estimates of overall survival (OS), cancer-specific survival,
and recurrence-free survival stratified by NLR were provided by the Kaplan-Meier
method. Cox regression models were performed to determine predictors of survival
and recurrence. Logistic regression models were used to identify factors
associated with pathologic node-positivity. RESULTS AND LIMITATIONS: The cut-off
point value was determined to be 3. Median OS was significantly shorter for
patients with NLR >=3 than those with NLR <3 (30 vs 158 mo, p<0.001). NLR >=3 was
an independent predictor of worse OS (hazard ratio=2.48; 95% confidence interval
[CI]: 1.02-6.06, p=0.046). On univariable analysis, NLR >=3 was associated with
an increased risk of pN+ disease (odds ratio [OR]=3.75; 95% CI: 1.30-10.81,
p=0.014). However, on multivariable analysis adjusted for primary tumor grade,
lymphovascular invasion, clinical N stage, and neoadjuvant treatment receipt, the
association between NLR and pN+ disease was no longer significant (OR=3.66; 95%
CI: 0.82-16.42, p=0.091). The retrospective design and limited size of the study
are acknowledged limitations. CONCLUSIONS: Pretreatment NLR is an independent
predictor of OS in PSCC patients undergoing ILND and highlights the association
between systemic inflammation and survival. Our data suggests that a simple
biomarker of inflammation can serve as a prognosticator in PSCC. PATIENT SUMMARY:
Penile cancer is a rare malignancy in North America and Europe. Therefore, there
is a lack of prognostic parameters to help predict oncologic and survival
outcomes. In this report, patients with an elevated neutrophil-to-lymphocyte
ratio had an increased risk of mortality.
PMID- 29937331
TI - Can Health Literacy be Determined From the Nutritional Information on an Ice
Cream Wrapping?
PMID- 29937332
TI - An analytical model to design circumferential clasps for laser-sintered removable
partial dentures.
AB - OBJECTIVE: Clasps of removable partial dentures (RPDs) often suffer from plastic
deformation and failure by fatigue; a common complication of RPDs. A new
technology for processing metal frameworks for dental prostheses based on laser
sintering, which allows for precise fabrication of clasp geometry, has been
recently developed. This study sought to propose a novel method for designing
circumferential clasps for laser-sintered RPDs to avoid plastic deformation or
fatigue failure. METHODS: An analytical model for designing clasps with
semicircular cross-sections was derived based on mechanics. The Euler-Bernoulli
elastic curved beam theory and Castigliano's energy method were used to relate
the stress and undercut with the clasp length, cross-sectional radius, alloy
properties, tooth type, and retention force. Finite element analysis (FEA) was
conducted on a case study and the resultant tensile stress and undercut were
compared with the analytical model predictions. Pull-out experiments were
conducted on laser-sintered cobalt-chromium (Co-Cr) dental prostheses to validate
the analytical model results. RESULTS: The proposed circumferential clasp design
model yields results in good agreement with FEA and experiments. The results
indicate that Co-Cr circumferential clasps in molars that are 13mm long engaging
undercuts of 0.25mm should have a cross-section radius of 1.2mm to provide a
retention of 10N and to avoid plastic deformation or fatigue failure. However,
shorter circumferential clasps such as those in premolars present high stresses
and cannot avoid plastic deformation or fatigue failure. SIGNIFICANCE: Laser
sintered Co-Cr circumferential clasps in molars are safe, whereas they are
susceptible to failure in premolars.
PMID- 29937333
TI - Effect of an acidic sodium salt on the polymerization behavior of self-adhesive
resin cements formulated with different adhesive monomers.
AB - OBJECTIVE: To determine the influence of benzenesulfinic acid sodium salt 98%
(BAS) and the activation mode on the polymerization behavior of experimental self
adhesive resin cements (SARCs) formulated with distinct self-etch methacrylates.
MATERIALS AND METHODS: Three catalyst-pastes using different self-etch
methacrylates (2MP - bis 2-(methacryloyloxy) ethyl phosphate; 4META - 4
methacryloxyethyl trimellitic acid anhydride; and GDMAP - 1,3-glycerol
dimethacrylate phosphate) and four base-pastes were formulated from the
incorporation of different amounts of BAS associated to N-N-dihydroxyethyl-p
toluidine (DHPT). BAS/DHPT ratios were blended respectively based on the
following final weight (wt%): control (0.0;2.0%), BP1 (0.5;1.5%), BP2 (0.8;1.2%)
and BP3 (1.0;1.0%). Real-time polymerization kinetics (KP) was assessed for 10min
by FTIR spectroscopy. Maximum rate of polymerization (Rpmax) was obtained from
the first derivative of the curve conversion versus time. Degree of conversion
(DC) was determined over 10min and after 24h. SARCs were tested in self and dual
activation modes. Data of Rpmax and DC 24h were respectively analyzed by two-way
ANOVA followed by Tukey's method (alpha=0.05). RESULTS: All factors and their
interactions were statistically significant (p<0.01). BAS caused an increase in
DC in the first minutes of the KP analysis, especially in self-activated groups.
After 24h, all groups showed higher DC than those observed in the first 10min. In
general, the addition of BAS increased the Rpmax. The GDMAP-based materials group
showed the highest Rpmax values when exposed to light but self-activated
formulations with GDMAP or 2MP showed the lowest Rpmax. SIGNIFICANCE: The
addition of BAS increased the degree of conversion of SARCs in the first minutes
and 24h after the polymerization reaction. This finding showed the importance of
adding this type of salt during resin cement production to achieve better
polymerization in the first minutes of the luting procedure specially when light
exposure is not possible.
PMID- 29937334
TI - [Genomic characterization of head and neck squamous cell carcinoma: Impact and
challenges for therapeutic management].
AB - Squamous cell carcinomas are the most frequent subgroup among head and neck
malignant tumors (HNSCC). Tobacco (+/-alcohol) and HPV infection, the two main
risk factors, define two entities with distinct anatomo-clinical and genetic
features. HPV-positive, non-tobacco-related HNSCCs are associated with a better
prognosis, a rather simple genomic profile, frequent activating mutations of
genes involved in pi3kinase-pathway, and the scarcity of mutations of tumor
suppressor genes. HPV-negative, tobacco-related HNSCC are genetically more
complex, are characterized by almost mandatory inactivating mutations/deletions
of tumor suppressor genes (TP53, CDKN2A) and the possible, but less frequent,
activating mutations or amplifications of some oncogenes that encode for cell
cycle proteins or receptors with tyrosine kinase activity. This review describes
the genetic features of HNSCC and discusses how these abnormalities could be
incorporated into a therapeutic approach.
PMID- 29937335
TI - ?
PMID- 29937337
TI - Excess Cost and Healthcare Resources Associated With Delayed Diagnosis of Charcot
Foot.
AB - The purpose of the present study was to demonstrate the effect of a delayed
diagnosis of Charcot foot on acute care cost and usage. We used International
Classification of Disease, Ninth Revision, Clinical Modification codes, and the
California Office for Statewide Health Planning and Development 2009 to 2012
public patient discharge files to identify patients with type 2 diabetes mellitus
and Charcot foot. The costs and length of stay were compared for those with a
diagnosis of Charcot foot on admission compared with those who received a delayed
diagnosis of Charcot foot before discharge. Patient demographic data, diagnoses
often mistaken for Charcot foot, and procedures often performed for Charcot foot
were assessed to determine the potential effect on costs and length of stay in
Charcot foot subjects. A delayed Charcot foot diagnosis was associated with 10.8%
greater inpatient costs and 12.1% longer length of stay. These patients required
greater resource usage owing to the significantly greater number of procedures
performed. A significantly greater number of patients underwent lower extremity
amputation when the diagnosis was delayed, resulting in a 30.4% increase in costs
and 31.6% longer length of stay. A greater rate of diabetic foot ulcers, foot
infections, and osteomyelitis was also observed; however, the cost was only
affected by osteomyelitis, and the length of stay was not significantly affected.
A delayed diagnosis of Charcot foot at admission resulted in significantly
increased acute care costs and longer lengths of stay.
PMID- 29937336
TI - [Early postsurgical temozolomide treatment in newly diagnosed bad prognosis
glioblastoma patients: Feasibility study].
AB - INTRODUCTION: Despite the combined adjuvant treatment of radiotherapy plus
chemotherapy with temozolomide (TMZ) followed by 6 cycles of temozolomide after
surgery, the prognosis of patients with glioblastoma remains poor. We conducted a
monocentric prospective study to explore the tolerance and potential efficacy of
an early temozolomide cycle after surgery. METHOD: Patients with newly diagnosed
glioblastoma (unmutated IDH1) and of poor prognosis (age>50 years, biopsy or
partial resection or unmethylated MGMT promoter) were prospectively included from
June 2014 to 2017. They all received a cycle of 5 days of temozolomide between
surgery and the combined adjuvant treatment. RESULTS: Twelve patients of median
age 64.5 years (45-73) were included in the study. The median doses of
temozolomide administered were respectively 265mg (225-300) for the early cycle;
130mg (110-150) for the concomitant treatment and 310mg (225-400) for the
adjuvant one. Side effects during treatment were grade III lymphopenia, grade III
neutropenia, fatigue and nausea/vomiting respectively in 4, 1, 7 and 5 patients.
Progression-free survival and overall survival were respectively 90% and 91.7% at
6 months; 58.3 and 71.3% at 12 months; 31.1 and 71.3% at 18 months. CONCLUSION:
Early postsurgical temozolomide treatment prior to standard adjuvant therapy for
poor prognosis glioblastoma patients in our small prospective series presents
toxicity and survival similar to those published in the literature for the
general population of glioblastoma. These encouraging results should be confirmed
by a multicentric study comparing this regiment with the standard treatment.
PMID- 29937338
TI - Distally Based Medial Plantar Flap: A Classification of the Surgical Techniques.
AB - The proximally based medial plantar flap is considered to be the reference
standard for heel reconstruction. Although less well-studied, a distally based
medial plantar flap is a suitable alternative when used to cover a distal foot
defect, especially of the hallux, first metatarsal, or metatarsophalangeal joint.
Our objective was to provide a complete description and propose a classification
of the different surgical procedures used to harvest this flap. A review of the
data reported in the MEDLINE database until May 2017 concerning the distally
based medial plantar flap was performed. We have illustrated the different
surgical procedures through a case series. Three approaches or "types" of flap
have been described, and we have proposed a classification for reconstructive
surgeons. In type 1, the plantar pedicle is ligatured before division into the
medial and lateral plantar artery. In type 2, the medial plantar pedicle is cut
proximally just after division. In type 3, the flap is harvested to include the
fasciocutaneous perforator vessels, as an advancement flap or a propeller
perforator flap. A distally based medial plantar flap affords adequate and
reliable coverage of the weightbearing zone. Because the donor site drawbacks are
minimal, this flap is a useful option for distal foot reconstruction, and
reconstructive surgeons should remember this flap. The type 1 flap appears to be
associated with a minimal risk of flap necrosis, even in those with diabetes or
arteriopathy, and can cover even the most distal defect.
PMID- 29937339
TI - Reconstruction of Neglected Flexor Hallucis Longus Tendon Rupture: A Case Report.
AB - Isolated rupture of the flexor hallucis longus tendon is an unusual injury. We
present the case of a neglected flexor hallucis longus tendon closed traumatic
rupture at the plantar aspect of the first phalangeal head of the great toe in a
middle-age male. The injury occurred while he was dancing. Because end-to-end
tendon suture was impossible, the ensuing gap was repaired using a free plantaris
tendon graft. We present the operative repair benefit of the flexor hallucis
longus tendon rupture to regain the function and strength of the interphalangeal
joint of the hallux, avoid extension of the distal phalanx, and maintain the
longitudinal arch of the foot.
PMID- 29937340
TI - Contrast-enhanced spectral mammography (CESM).
AB - Contrast-enhanced spectral mammography (CESM) is a valuable tool in the diagnosis
and staging of primary breast cancer. It combines an iodinated contrast agent
with conventional mammography to improve diagnostic accuracy, particularly in
women with denser parenchymal background patterns. This review describes the CESM
technique, reviews performance compared to conventional mammography and magnetic
resonance imaging, assesses its role in the diagnosis and staging of primary
breast cancer, and investigates its potential as a screening tool.
PMID- 29937341
TI - ATRX Promotes DNA Repair Synthesis and Sister Chromatid Exchange during
Homologous Recombination.
AB - ATRX is a chromatin remodeler that, together with its chaperone DAXX, deposits
the histone variant H3.3 in pericentromeric and telomeric regions. Notably, ATRX
is frequently mutated in tumors that maintain telomere length by a specific form
of homologous recombination (HR). Surprisingly, in this context, we demonstrate
that ATRX-deficient cells exhibit a defect in repairing exogenously induced DNA
double-strand breaks (DSBs) by HR. ATRX operates downstream of the Rad51 removal
step and interacts with PCNA and RFC-1, which are collectively required for DNA
repair synthesis during HR. ATRX depletion abolishes DNA repair synthesis and
prevents the formation of sister chromatid exchanges at exogenously induced DSBs.
DAXX- and H3.3-depleted cells exhibit identical HR defects as ATRX-depleted
cells, and both ATRX and DAXX function to deposit H3.3 during DNA repair
synthesis. This suggests that ATRX facilitates the chromatin reconstitution
required for extended DNA repair synthesis and sister chromatid exchange during
HR.
PMID- 29937343
TI - Mechanical Strength of the Proximal Femur After Arthroscopic Osteochondroplasty
for Femoroacetabular Impingement: Finite Element Analysis and 3-Dimensional Image
Analysis.
AB - PURPOSE: To examine the influence of femoral neck resection on the mechanical
strength of the proximal femur in actual surgery. METHODS: Eighteen subjects who
received arthroscopic cam resection for cam-type femoroacetabular impingement
(FAI) were included. Finite element analyses (FEAs) were performed to calculate
changes in simulative fracture load between pre- and postoperative femur models.
The finite element femur models were constructed from computed tomographic
images; thus, the models represented the shape of the original femur, including
the bone resection site. Three-dimensional image analysis of the bone resection
site was performed to identify morphometric factors that affect strength in the
postoperative femur model. Four oblique sagittal planes running perpendicular to
the femoral neck axis were used as reference planes to measure the bone resection
site. RESULTS: At the transcervical reference plane, both the bone resection
depth and the cross-sectional area at the resection site correlated strongly with
postoperative changes in the simulated fracture load (R2 = 0.6, P = .0001).
However, only resection depth was significantly correlated with the simulated
fracture load at the reference plane for the head-neck junction. The resected
bone volume did not correlate with the postoperative changes in the simulated
fracture load. CONCLUSIONS: The results of our FEA suggest that the bone
resection depth measured at the head-neck junction and transcervical reference
plane correlates with fracture risk after osteochondroplasty. By contrast, bone
resection at more proximal areas did not have a significant effect on the
postoperative femur model strength in our FEA. The total volume of resected bone
was also not significantly correlated with postoperative changes in femur model
strength. CLINICAL RELEVANCE: This biomechanical study using FEA suggest that
there is a risk of femoral neck fracture after arthroscopic cam resection,
particularly when the resected lesion is located distally.
PMID- 29937342
TI - Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome
Chaperone Activity of FANCD2.
AB - Components of the Fanconi anemia and homologous recombination pathways play a
vital role in protecting newly replicated DNA from uncontrolled nucleolytic
degradation, safeguarding genome stability. Here we report that histone
methylation by the lysine methyltransferase SETD1A is crucial for protecting
stalled replication forks from deleterious resection. Depletion of SETD1A
sensitizes cells to replication stress and leads to uncontrolled DNA2-dependent
resection of damaged replication forks. The ability of SETD1A to prevent
degradation of these structures is mediated by its ability to catalyze
methylation on Lys4 of histone H3 (H3K4) at replication forks, which enhances
FANCD2-dependent histone chaperone activity. Suppressing H3K4 methylation or
expression of a chaperone-defective FANCD2 mutant leads to loss of RAD51
nucleofilament stability and severe nucleolytic degradation of replication forks.
Our work identifies epigenetic modification and histone mobility as critical
regulatory mechanisms in maintaining genome stability by restraining nucleases
from irreparably damaging stalled replication forks.
PMID- 29937344
TI - The Influence of Bone Loss on Glenoid Version Measurement: A Computer-Modeled
Cadaveric Analysis.
AB - PURPOSE: To characterize how increasing computed tomography (CT)-quantified
glenoid bone loss influences measured version. METHODS: Six embalmed cadaveric
shoulders were used for this study. Glenoid bone defects were computer modeled in
cadaveric shoulders; CT images were obtained and segmented using OsiriX software,
creating 3-dimensional en face glenoids. Glenoid defects were made on CT images
of intact glenoids superimposed with a glenoid clock face viewed en face to
simulate anterior and posterior bone loss. Bony defects in various positions
comprising 3%, 9.5%, and 19.5% were created posteriorly. Best-fit circles were
superimposed to represent 10% and 25% defects anteriorly. Version was measured
using the Friedman method. RESULTS: The average glenoid version measured 4
degrees of retroversion, 2 degrees after 10% anterior bone loss, and neutral
version in the 25% bone loss group. Version was significantly altered when we
compared intact glenoids versus 10% and 25% anterior glenoid bone loss (P <
.001). Increasing from 10% to 25% bone loss showed a significant difference in
measured version (P = .025). Posterior defects from the 6:30 to 8:30 clock-face
position averaged 4.6 degrees of retroversion; from the 6:30 to 9:30 clock-face
position, 6.2 degrees of retroversion; and from the 6:30 to 10:30 clock-face
position, 8.7 degrees of retroversion. When comparing glenoid defects at the
6:30 to 8:30 clock-face position with those involving the 6:30 to 9:30 and 6:30
to 10:30 clock-face positions (P < .001), a 1 degrees correction may be used for
every 5% of bone loss to account for version changes seen with bone loss.
CONCLUSIONS: In this cadaveric analysis, glenoid version was altered in the
setting of increasing posterior and anterior bone loss. A correction factor may
be considered to account for this. When comparing glenoid defects at the 6:30 to
8:30 clock-face position with those involving the 6:30 to 9:30 and 6:30 to 10:30
clock-face positions (P < .001), a 1 degrees correction may be used for every 5%
of bone loss to account for version changes seen with bone loss. CLINICAL
RELEVANCE: This cadaveric study shows that glenoid bone loss alters glenoid
version, as measured by CT, in a meaningful way. This information is important in
managing anterior and posterior shoulder instability, and correction of measured
version should be considered in this setting to provide an accurate and
comprehensive evaluation.
PMID- 29937345
TI - Shoulder Arthroscopy With Versus Without Suprascapular Nerve Release: Clinical
Outcomes and Return to Sport Rate in Elite Overhead Athletes.
AB - PURPOSE: To compare the clinical outcomes and return to sport rate between elite
overhead athletes who underwent shoulder arthroscopy and decompression of the
suprascapular nerve (SSN) versus overhead athletes who underwent shoulder
arthroscopy without SSN release. METHODS: From 2007 to 2014, high-level overhead
athletes diagnosed with a rotator cuff tear and/or a glenoid labral lesion and
SSN entrapment were included in the study if their symptoms did not improve with
nonoperative treatment and if they agreed to undergo surgery and participate.
Their preoperative University of California at Los Angeles (UCLA) shoulder score,
bilateral postoperative Constant scores, postoperative UCLA score, and return to
sport rate were evaluated and compared with those of a group of elite athletes
who had a similar diagnosis but refused to undergo SSN decompression during
shoulder arthroscopy. RESULTS: Thirty-five athletes (25 male, 10 female) were
included in the SSN decompression group (group 1), and 21 athletes were included
in the non-SSN decompression group (group 2). The mean age was 27 years (range:
19-34) and 24 years (range: 21-32) in group 1 and group 2, respectively (P =
.56). The mean follow-up time was 38.4 months (24-50 months) in group 1 and 42.2
months (26-53 months) in group 2 (P = .09). Both groups had significantly
improved UCLA scores after surgery (P < .05). The postoperative UCLA (P = .01)
and Constant scores (P < .001) were significantly higher in the SSN decompression
group. The mean difference in Constant score between the affected and the
unaffected side was 4 points (range: 2-12) in the SSN decompression group and 8
points (range: 4-14) in the non-SSN decompression group postoperatively (P =
.0002). In both groups, 100% of patients reached the patient acceptable symptom
state value for Constant score at follow-up. For the UCLA score, patients who
underwent SSN decompression had significantly higher pre- to postoperative
improvement than the nondecompression group (P = .016). The return to sport rate
was 97% in group 1 and 84% in group 2. The mean length of career was 2.1 years
(range: 1.5-2.4 years) and 2.3 years (range: 1.2-3.2 years) in group 1 and group
2, respectively. CONCLUSIONS: In elite overhead athletes with shoulder pathology
and SSN entrapment, combined shoulder arthroscopy and SSN release yield superior
clinical outcomes, greater improvement in UCLA score, and a higher return to
sport rate than shoulder arthroscopy without SSN decompression. Regardless of SSN
treatment, both groups achieved the patient acceptable symptom state after
shoulder arthroscopy. LEVEL OF EVIDENCE: Level III, comparative case series.
PMID- 29937346
TI - Single-Bundle Versus Double-Bundle Anterior Cruciate Ligament Reconstruction-5
Year Results.
AB - PURPOSE: To compare anatomic single-bundle (SB) with double-bundle (DB) anterior
cruciate ligament reconstruction (ACL-R) and to evaluate the respective clinical
outcome results. METHODS: In a prospective randomized study, 64 patients were
included and separated into 2 groups. Anatomic SB and DB ACL-Rs were performed
with hamstring tendons. Five years after surgery, the follow-up (FU) examination
comprised International Knee Documentation Committee (IKDC) 2000, Laxitester
(ORTEMA Sport Protection, Markgroeningen, Germany) measurement, and radiograph
evaluation. Power calculation was performed to achieve a 95% confidence interval
and 80% power on the base of 7-point IKDC subjective difference between the
groups. RESULTS: A total of 53 patients (83% FU) were examined at 63.2 +/- 4.7
months after surgery: 28 patients in the DB group and 25 patients in the SB
group. IKDC subjective (SB: 92.8 +/- 6.2, DB: 91.6 +/- 7.1; P = .55) and
objective scores (grade A SB/DB 20%/25%, B SB/DB 72%/57%, C SB/DB 8%/18%, D SB/DB
4%/0%; P = .45) showed no differences comparing both groups. The Laxitester
measurements showed no significant difference in regard to anterior-posterior
translation in neutral, internal, and external rotation or to rotation angles (P
= .79). No difference was seen between the groups regarding osteoarthritic
changes and tunnel widening. CONCLUSIONS: At the 5-year FU, no advantage for
either the DB or SB technique in ACL-R can be seen with regard to patient-related
and objective outcome measures. LEVEL OF EVIDENCE: Level I, prospective
randomized controlled clinical trial.
PMID- 29937347
TI - The Earth's Magnetic Field and Visual Landmarks Steer Migratory Flight Behavior
in the Nocturnal Australian Bogong Moth.
AB - Like many birds [1], numerous species of nocturnal moths undertake spectacular
long-distance migrations at night [2]. Each spring, billions of Bogong moths
(Agrotis infusa) escape hot conditions in different regions of southeast
Australia by making a highly directed migration of over 1,000 km to a limited
number of cool caves in the Australian Alps, historically used for aestivating
over the summer [3, 4]. How moths determine the direction of inherited migratory
trajectories at night and locate their destination (i.e., navigate) is currently
unknown [5-7]. Here we show that Bogong moths can sense the Earth's magnetic
field and use it in conjunction with visual landmarks to steer migratory flight
behavior. By tethering migrating moths in an outdoor flight simulator [8], we
found that their flight direction turned predictably when dominant visual
landmarks and a natural Earth-strength magnetic field were turned together, but
that the moths became disoriented within a few minutes when these cues were set
in conflict. We thus conclude that Bogong moths, like nocturnally migrating birds
[9], can use a magnetic sense. Our results represent the first reliable
demonstration of the use of the Earth's magnetic field to steer flight behavior
in a nocturnal migratory insect.
PMID- 29937348
TI - Differential Role of Prefrontal and Parietal Cortices in Controlling Level of
Consciousness.
AB - Consciousness is determined both by level (e.g., being awake versus being
anesthetized) and content (i.e., the qualitative aspects of experience).
Subcortical areas are known to play a causal role in regulating the level of
consciousness [1-9], but the role of the cortex is less well understood. Clinical
and correlative data have been used both to support and refute a role for
prefrontal and posterior cortices in the level of consciousness [10-22]. The
prefrontal cortex has extensive reciprocal connections to wake-promoting centers
in the brainstem and diencephalon [23, 24], and hence is in a unique position to
modulate level of consciousness. Furthermore, a recent study suggested that the
prefrontal cortex might be important in regulating level of consciousness [25]
but causal evidence, and a comparison with more posterior cortical sites, is
lacking. Therefore, to test the hypothesis that prefrontal cortex plays a role in
regulating level of consciousness, we attempted to reverse sevoflurane anesthesia
by cholinergic or noradrenergic stimulation of the prefrontal prelimbic cortex
and two areas of parietal cortex in rat. General anesthesia was defined by loss
of the righting reflex, a widely used surrogate measure in rodents. We
demonstrate that cholinergic stimulation of prefrontal cortex, but not parietal
cortex, restored wake-like behavior, despite continuous exposure to clinically
relevant concentrations of sevoflurane anesthesia. Noradrenergic stimulation of
the prefrontal and parietal areas resulted in electroencephalographic activation
but failed to produce any signs of wake-like behavior. We conclude that
cholinergic mechanisms in prefrontal cortex can regulate the level of
consciousness.
PMID- 29937349
TI - Electrostatic Tuning of a Potassium Channel in Electric Fish.
AB - Molecular variation contributes to the evolution of adaptive phenotypes, though
it is often difficult to understand precisely how. The adaptively significant
electric organ discharge behavior of weakly electric fish is the direct result of
biophysical membrane properties set by ion channels. Here, we describe a voltage
gated potassium-channel gene in African electric fishes that is under positive
selection and highly expressed in the electric organ. The channel produced by
this gene shortens electric organ action potentials by activating quickly and at
hyperpolarized membrane potentials. The source of these properties is a derived
patch of negatively charged amino acids in an extracellular loop near the voltage
sensor. We demonstrate that this negative patch acts by contributing to the
global surface charge rather than by local interactions with specific amino acids
in the channel's extracellular face. We suggest a more widespread role for this
loop in the evolutionary tuning of voltage-dependent channels.
PMID- 29937350
TI - Zebrafish Differentially Process Color across Visual Space to Match Natural
Scenes.
AB - Animal eyes have evolved to process behaviorally important visual information,
but how retinas deal with statistical asymmetries in visual space remains poorly
understood. Using hyperspectral imaging in the field, in vivo 2-photon imaging of
retinal neurons, and anatomy, here we show that larval zebrafish use a highly
anisotropic retina to asymmetrically survey their natural visual world. First,
different neurons dominate different parts of the eye and are linked to a
systematic shift in inner retinal function: above the animal, there is little
color in nature, and retinal circuits are largely achromatic. Conversely, the
lower visual field and horizon are color rich and are predominately surveyed by
chromatic and color-opponent circuits that are spectrally matched to the dominant
chromatic axes in nature. Second, in the horizontal and lower visual field,
bipolar cell terminals encoding achromatic and color-opponent visual features are
systematically arranged into distinct layers of the inner retina. Third, above
the frontal horizon, a high-gain UV system piggybacks onto retinal circuits,
likely to support prey capture.
PMID- 29937351
TI - An Immune-Responsive Cytoskeletal-Plasma Membrane Feedback Loop in Plants.
AB - Cell wall appositions (CWAs) are produced reactively by the plant immune system
to arrest microbial invasion through the local inversion of plant cell growth.
This process requires the controlled invagination of the plasma membrane (PM) in
coordination with the export of barrier material to the volume between the plant
PM and cell wall. Plant actin dynamics are essential to this response, but it
remains unclear how exocytosis and the cytoskeleton are linked in space and time
to form functional CWAs. Here, we show that actin-dependent trafficking to immune
response sites of Arabidopsis thaliana delivers membrane-integrated FORMIN4,
which in turn contributes to local cytoskeletal dynamics. Total internal
reflection fluorescence (TIRF) microscopy combined with controlled induction of
FORMIN4-GFP expression reveals a dynamic population of vesicular bodies that
accumulate to form clusters at the PM through an actin-dependent process.
Deactivation of FORMIN4 and its close homologs partially compromises subsequent
defense and alters filamentous actin (F-actin) distribution at mature CWAs. The
localization of FORMIN4 is stable and segregated from the dynamic traffic of the
endosomal network. Moreover, the tessellation of FORMIN4 at the PM with meso
domains of PEN3 reveals a fine spatial segregation of destinations for actin
dependent immunity cargo. Together, our data suggest a model where FORMIN4 is a
spatial feedback element in a multi-layered, temporally defined sequence of
cytoskeletal response. This positional feedback makes a significant contribution
to the distribution of actin filaments at the dynamic CWA boundary and to the
outcomes of pre-invasion defense.
PMID- 29937352
TI - Multiple Scales of Representation along the Hippocampal Anteroposterior Axis in
Humans.
AB - The ability to represent the world accurately relies on simultaneous coarse and
fine-grained neural information coding, capturing both gist and detail of an
experience. The longitudinal axis of the hippocampus may provide a gradient of
representational granularity in spatial and episodic memory in rodents and humans
[1-8]. Rodent place cells in the ventral hippocampus exhibit significantly larger
place fields and greater autocorrelation than those in the dorsal hippocampus [1,
9-11], which may underlie a coarser and slower changing representation of space
[10, 12]. Recent evidence suggests that properties of cellular dynamics in
rodents can be captured with fMRI in humans during spatial navigation [13] and
conceptual learning [14]. Similarly, mechanisms supporting granularity along the
long axis may also be extrapolated to the scale of fMRI signal. Here, we provide
the first evidence for separable scales of representation along the human
hippocampal anteroposterior axis during navigation and rest by showing (1)
greater similarity among voxel time courses and (2) higher temporal
autocorrelation in anterior hippocampus (aHPC), relative to posterior hippocampus
(pHPC), the human homologs of ventral and dorsal rodent hippocampus. aHPC voxels
exhibited more similar activity at each time point and slower signal change over
time than voxels in pHPC, consistent with place field organization in rodents.
Importantly, similarity between voxels was related to navigational strategy and
episodic memory. These findings provide evidence that the human hippocampus
supports an anterior-to-posterior gradient of coarse-to-fine spatiotemporal
representations, suggesting the existence of a cross-species mechanism, whereby
lower neural similarity supports more complex coding of experience.
PMID- 29937353
TI - Unconventional oil and gas chemicals and wastewater-impacted water samples
promote adipogenesis via PPARgamma-dependent and independent mechanisms in 3T3-L1
cells.
AB - Unconventional oil and natural gas (UOG) operations have contributed to a surge
in domestic oil and natural gas production in the United States, combining
horizontal drilling with hydraulic fracturing to unlock previously inaccessible
fossil fuel deposits. >1000 organic chemicals are used in the production process,
and wastewater is produced following injection and for the life of the producing
well. This wastewater is typically disposed of via injecting into disposal wells
for long-term storage, treatment and discharge from wastewater treatment plants,
and/or storage in open evaporation pits; however, wastewater spill rates are
reported at 2-20% of active well sites across regions, increasing concerns about
the environmental impacts of these wastewaters. This study assessed adipogenic
activity (both triglyceride accumulation and pre-adipocyte proliferation) for a
mixture of 23 commonly used UOG chemicals and a small subset of UOG wastewater
impacted surface water extracts from Colorado and West Virginia, using 3T3-L1
cells and a peroxisome proliferator activated receptor gamma (PPARgamma) reporter
assay. We report potent and efficacious adipogenic activity induced by both a
laboratory-created UOG chemical mixture and UOG-impacted water samples at
concentrations below environmental levels. We further report activation of
PPARgamma at similar concentrations for some samples, suggesting a causative
molecular pathway for the observed effects, but not for other adipogenic samples,
implicating PPARgamma-dependent and independent effects from UOG associated
chemicals. Taken together, these results suggest that UOG wastewater has the
potential to impact metabolic health at environmentally relevant concentrations.
PMID- 29937355
TI - Design, synthesis and biological evaluation of novel series of 2H
benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold derivatives as
PI3Kalpha inhibitors.
AB - The abnormal activation of PI3K signaling pathway leads to the occurrence of
various cancers. The PI3Kalpha is frequently mutated and overexpressed in many
human cancers. Therefore, the PI3Kalpha was considered as a promising target in
therapeutic treatment of cancer. In this study, two series of compounds
containing 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold
were synthesized and evaluated antiproliferative activities against three cancer
cell lines, including HCT-116, MDA-MB-231 and SNU638. Compound 7f with the most
potent antiproliferative activity was selected for further evaluation on normal
cells and PI3K kinase. Studies indicated that compound 7f could decrease the
phospho-Akt (T308) in a dose-dependent manner. Four key hydrogen bonding
interactions were found in the docking of 7f with PI3K enzyme. All the results
suggested that 7f was a potent PI3Kalpha inhibitor.
PMID- 29937356
TI - Toward an Ensemble View of Chromatosome Structure: A Paradigm Shift from One to
Many.
AB - There is renewed interest in linker histone (LH)-nucleosome binding and how LHs
influence eukaryotic DNA compaction. For a long time, the goal was to uncover
"the structure of the chromatosome," but recent studies of LH-nucleosome
complexes have revealed an ensemble of structures. Notably, the reconstituted LH
nucleosome complexes used in experiments rarely correspond to the sequence
combinations present in organisms. For a full understanding of the determinants
of the distribution of the chromatosome structural ensemble, studies must include
a complete description of the sequences and experimental conditions used, and be
designed to enable systematic evaluation of sequence and environmental effects.
PMID- 29937354
TI - Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma
Via Intercellular Transfer of Splicing Factors.
AB - Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic
cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling
between apoptotic and surviving cancer cells remain elusive. In this study, we
demonstrate that apoptotic GBM cells paradoxically promote proliferation and
therapy resistance of surviving tumor cells by secreting apoptotic extracellular
vesicles (apoEVs) enriched with various components of spliceosomes. apoEVs alter
RNA splicing in recipient cells, thereby promoting their therapy resistance and
aggressive migratory phenotype. Mechanistically, we identified RBM11 as a
representative splicing factor that is upregulated in tumors after therapy and
shed in extracellular vesicles upon induction of apoptosis. Once internalized in
recipient cells, exogenous RBM11 switches splicing of MDM4 and Cyclin D1 toward
the expression of more oncogenic isoforms.
PMID- 29937357
TI - Magnesium Activates Microsecond Dynamics to Regulate Integrin-Collagen
Recognition.
AB - Integrin receptors bind collagen via metal-mediated interactions that are
modulated by magnesium (Mg2+) levels in the extracellular matrix. Nuclear
magnetic resonance-based relaxation experiments, isothermal titration
calorimetry, and adhesion assays reveal that Mg2+ functions as both a structural
anchor and dynamic switch of the alpha1beta1 integrin I domain (alpha1I).
Specifically, Mg2+ binding activates micro- to millisecond timescale motions of
residues distal to the binding site, particularly those surrounding the salt
bridge at helix 7 and near the metal ion-dependent adhesion site. Mutagenesis of
these residues impacts alpha1I functional activity, thereby suggesting that Mg
bound alpha1I dynamics are important for collagen binding and consequent
allosteric rearrangement of the low-affinity closed to high-affinity open
conformation. We propose a multistep recognition mechanism for alpha1I-Mg
collagen interactions involving both conformational selection and induced-fit
processes. Our findings unravel the multifaceted role of Mg2+ in integrin
collagen recognition and assist in elucidating the molecular mechanisms by which
metals regulate protein-protein interactions.
PMID- 29937358
TI - Conformational States of ABC Transporter MsbA in a Lipid Environment Investigated
by Small-Angle Scattering Using Stealth Carrier Nanodiscs.
AB - Structural studies of integral membrane proteins (IMPs) are challenging, as many
of them are inactive or insoluble in the absence of a lipid environment. Here, we
describe an approach making use of fractionally deuterium labeled "stealth
carrier" nanodiscs that are effectively invisible to low-resolution neutron
diffraction and enable structural studies of IMPs in a lipidic native-like
solution environment. We illustrate the potential of the method in a joint small
angle neutron scattering (SANS) and X-ray scattering (SAXS) study of the ATP
binding cassette (ABC) transporter protein MsbA solubilized in the stealth
nanodiscs. The data allow for a direct observation of the signal from the
solubilized protein without contribution from the surrounding lipid nanodisc. Not
only the overall shape but also differences between conformational states of MsbA
can be reliably detected from the scattering data, demonstrating the sensitivity
of the approach and its general applicability to structural studies of IMPs.
PMID- 29937359
TI - Short-term glucose variability in adults with Type 1 diabetes does not differ
between insulin pump and multiple daily injection users - a masked continuous
glucose monitoring study in clinical practice.
PMID- 29937360
TI - A SIMPL application to assess oral medicine residents' performance and level of
autonomy.
AB - OBJECTIVES: The aim of this study was to evaluate a smartphone application,
SIMPL, to optimize faculty guidance and oral medicine residents' performance, and
to measure resident-faculty agreement for performance and supervision levels.
STUDY DESIGN: Raters used the 5-level "Performance" scale to assess resident's
readiness for independent practice and the 4-level Zwisch scale to assess faculty
guidance, between June 2016 and June 2017. Junior residents were trainees with
less than 18 months of training, and senior residents had more than 18 months of
training. Descriptive statistics were used to analyze supervision and autonomy.
Performance and supervision agreement was estimated as percentage-agreement and
measured using kappa and 95% confidence intervals. RESULTS: A total of 660
evaluations were performed by 6 residents and 6 faculty members. Senior residents
received higher performance scores compared with junior residents (P for trend <
.01). In terms of complexity of cases and level of supervision, there were no
significant differences between juniors and seniors (P = .69 and P = .39,
respectively). Residents were "practice ready" or greater than for 80% cases.
Residents received meaningful autonomy for 64.8% cases. Faculty-resident
concordance was 86.1% for performance (with kappa of 0.77 [95% CI 66.1%-87.6%])
and 92.4% for supervision (with kappa of 0.84 [95% CI 80%-88%]). CONCLUSIONS:
SIMPL can feasibly be used for real-time assessment of residents' performance and
autonomy.
PMID- 29937361
TI - Frequency and type of ponticulus posticus in a longitudinal sample of
nonorthodontically treated patients: relationship with gender, age, skeletal
maturity, and skeletal malocclusion.
AB - OBJECTIVES: The aim of this study was to assess the frequency and type of
ponticulus posticus and to evaluate its relationship to gender, chronologic age,
skeletal maturity, and skeletal malocclusion. STUDY DESIGN: The sample included
the longitudinal lateral cephalograms of 734 patients (378 males and 356 females)
retrieved from the American Association of Orthodontists Craniofacial Growth
Legacy Collection. The presence of ponticulus posticus (complete and partial
forms) was assessed by visual inspection, and the cervical vertebral maturation
method was used to determine the skeletal maturation stage. The presence and type
(complete or partial) of ponticulus posticus were assessed by gender, age at
first appearance of ponticulus posticus, skeletal maturation stage as determined
by the cervical vertebral maturation method, and skeletal malocclusion. RESULTS:
The overall prevalence of ponticulus posticus was 12.6% (93 of 734) with complete
and partial forms observed respectively in 8.7% (64 of 734) and 3.9% (29 of 734)
of the sample. Both forms of ponticulus posticus occurred mainly in the age range
of 7 to 13 years (P = .04). No differences were found in groups based on gender,
skeletal maturity stages, or skeletal malocclusion (P > .05). However,
approximately 90% of ponticulus posticus occurred before and after the
circumpubertal stage. CONCLUSIONS: Ponticulus posticus should be expected mainly
during childhood and the pubertal age. This may support the theory of a genetic
cause of this vertebral anomaly.
PMID- 29937362
TI - The trapezius perforator flap: Versatility for locoregional reconstruction.
AB - Only a few surgical choices are available for cervical and thoracic spine
coverage. The trapezius perforator flap is relatively unknown and only a few
authors have published on this subject. In this article, we report on four
clinical cases where a trapezius perforator flap was used either as a propeller
flap, as a tunnelized island flap, or as a supercharged flap for cervical spine,
thoracic spine and anterior cervical defects. Harvesting this flap is quite
simple and enables high quality reconstruction with low donor-site morbidity in
complex situations.
PMID- 29937363
TI - answer for the "Diagnosis and staging of solid pseudopapillary neoplasms of the
pancreas: the role of 18 1 F-FDG PET/CT scan".
PMID- 29937364
TI - The adenosine, adrenergic and opioid pathways in the regulation of insulin
secretion, beta cell proliferation and regeneration.
AB - Insulin, a key hormone produced by pancreatic beta cells precisely regulates
glucose metabolism in vertebrates. In type 1 diabetes, the beta cell mass is
destroyed, a process triggered by a combination of environmental and genetic
factors. This ultimately results in absolute insulin deficiency and dysregulated
glucose metabolism resulting in a number of detrimental pathophysiological
effects. The traditional focus of treating type 1 diabetes has been to control
blood sugar levels through the administration of exogenous insulin. Newer
approaches aim to replace the beta cell mass through pancreatic or islet
transplantation. Type 2 diabetes results from a relative insulin deficiency for
the prevailing insulin resistance. Treatments are generally aimed at reducing
insulin resistance and/or augmenting insulin secretion and the use of insulin
itself is often required. It is increasingly being recognized that the beta cell
mass is dynamic and increases insulin secretion in response to beta cell mitogens
and stress signals to maintain glycemia within a very narrow physiological range.
This review critically discusses the role of adrenergic, adenosine and opioid
pathways and their interrelationship in insulin secretion, beta cell
proliferation and regeneration.
PMID- 29937365
TI - Second generation optical coherence tomography: Preliminary experience in
pancreatic and biliary strictures.
AB - INTRODUCTION: Evaluation of indeterminate biliary strictures remains a diagnostic
challenge. Optical coherence tomography (OCT) provides in-vivo, wide-field, cross
sectional imaging at the microstructure level. We present the first preliminary
data using a second-generation OCT system using volumetric laser endomicroscopy
(VLE) in biliary and pancreatic duct strictures. METHODS: 10 consecutive patients
undergoing endoscopic retrograde cholangiopancreatography (ERCP) and OCT for
indeterminate biliary or pancreatic stricture evaluation were captured in a
registry. Following ductal cannulation and guidewire placement, an imaging probe
was advanced into the duct and images were interpreted in-vivo. Tissue sampling
with cytology brushing was performed in all cases. Demographics, procedural
information, imaging data, and histologic findings were collected. RESULTS: 8 had
biliary strictures and 2 had pancreatic duct strictures. VLE was successfully
performed in all patients (100%). Histology revealed malignancy in 3 patients
(cholangiocarcinoma) and benign disease in the remaining 7 patients, including 1
with primary sclerosing cholangitis (PSC). All 3 cholangiocarcinoma patients
demonstrated epithelial thickening with projections, a hyper-reflective surface
with shadowing, and layering effacement (loss of visualization and haziness of
inner mucosal layers). A PSC patient showed onion skin layering and hyper
reflective sub-surface structures but with preserved wall layering. Benign
biliary strictures showed clearly delineated epithelial layer and clear layering
in the inner mucosal layers as well as the presence of dilated hypo-reflective
structures. CONCLUSION: There may be characteristic VLE findings for malignant,
inflammatory, and benign biliary strictures.
PMID- 29937366
TI - Aqueous volume loss associated with occlusion break surge in phacoemulsifiers
from 4 different manufacturers.
AB - PURPOSE: To evaluate aqueous volume losses associated with occlusion breaks at
varying vacuum limits in phacoemulsification systems from 4 different
manufacturers. SETTING: Alcon Research Ltd., Lake Forest, California, USA.
DESIGN: Experimental study. METHODS: The anterior chamber was modeled using the
spring eye model. Systems tested included the Centurion, Whitestar Signature,
Stellaris PC, and EVA. Occlusion breaks were actuated at vacuum limits of 200,
300, 400, 500, and 600 mm Hg and a target intraocular pressure of 55 mm Hg.
RESULTS: The model eye piston reached its measurement limit just below 600 mm Hg
on the EVA and just above 400 mm Hg on the Stellaris PC. Higher vacuum limits
could not be tested on these 2 units. Surge volumes varied from 17 to 77 MUL on
the Centurion, 30 to 103 MUL on the Whitestar Signature, 67 MUL to 163 MUL on the
Stellaris PC, and 47 to 165 MUL on the EVA. Assuming an average phakic eye
aqueous volume of 250 MUL, these MUL values correspond to percent aqueous volume
losses of 7% to 31% on the Centurion, 12% to 41% on the Whitestar Signature, 27%
to 65% on the Stellaris PC, and 19% to 66% on the EVA. Surge responses increased
on all machines with each increment in vacuum limit. The Centurion had the lowest
surge volumes across all vacuum limits. CONCLUSIONS: Occlusion break surge
volumes vary considerably across phacoemulsification platforms. Severe chamber
shallowing might occur if an occlusion break occurs under high vacuum on some
systems.
PMID- 29937367
TI - Are facial injuries really different?
PMID- 29937368
TI - Sentinel lymph node biopsy in melanoma: Which hot nodes should be harvested and
is blue dye really necessary?
AB - OBJECTIVES: The '10% rule' has become widely accepted by surgeons performing
sentinel lymph node biopsy (SLNB) for melanoma. The purpose of this study was to
compare the '10% rule' with alternative node harvesting criteria. In particular,
we were interested to see whether the use of blue dye had any impact on the
sensitivity of the test and whether it is necessary to remove all hot nodes.
METHODS: We reviewed 537 SLNBs performed for primary melanoma from 2009-2015.
SLNB was offered to all patients with 1-4 mm Breslow thickness melanoma and
sentinel nodes were harvested according to the '10% rule'. RESULTS: One hundred
sixteen patients (22%) had at least one positive sentinel node and there were 45
positive nodal basins from which more than one sentinel node had been harvested.
Excluding blue dye and sampling only hot nodes would have enabled a 5% reduction
in nodes harvested, without any compromise in the sensitivity of the test.
However, applying harvesting criteria whereby not all hot nodes are taken was
associated with a loss of sensitivity, with positive sentinel nodes being missed
and patients understaged. CONCLUSIONS: Our data do not support the continued use
of blue dye in SLNB for melanoma, as it does not improve the sensitivity of the
test. This series adds to growing evidence, suggesting that the '10% rule' with
the inclusion of blue nodes should be reconsidered and that radiocolloid tracer
alone is sufficient for sentinel node localisation.
PMID- 29937369
TI - Smartphones for frugal three-dimensional scanning of the external ear with
application to microtia?.
PMID- 29937370
TI - Diagnostic consistency of cases from ADNI cohort metadata: methodological
considerations.
PMID- 29937371
TI - Postnatal quality of life - A content analysis of qualitative results to the
Mother-Generated Index.
AB - BACKGROUND: The Mother-Generated Index (MGI) assesses postnatal quality of life
(QoL) without providing a predefined checklist, thus offering mothers the
opportunity to identify areas of life affected by having a baby. AIM: To
identify: (a) details and particularities of areas of life affected after
childbirth and thus specific domains defining postnatal quality of life; (b)
changes in the importance of domains specifying QoL within the first weeks
postpartum; and (c) the potential role of cultural differences with regard to the
nature of QoL definitions. METHODS: Prospective, cross-cultural, longitudinal
survey. We applied a qualitative content analysis to Mother-Generated Index data
collected in Switzerland and Germany using combined deductively and inductively
category building. RESULTS: Women participated at three days (n=124) and six and
a half weeks (n=82) postpartum. Eleven domains were identified, each with several
subdomains: 'physical well-being' (e.g. fatigue), 'psychological well-being'
(e.g. happiness, emotional confusion), 'general well-being', 'motherhood' (e.g.
bonding with the baby), 'family and partnership' (e.g. time for partner and
children), 'social life' (e.g. friends, being isolated), 'everyday life' (e.g.
organisation daily routine), 'leisure' (e.g. less time), 'work life' (e.g.
worries about job), 'financial issues' (e.g. less money), and further aspects.
The most frequently indicated domains were 'motherhood' and 'family and
partnership'. Differences between the stages of assessment and countries were
identified. DISCUSSION: Mothers faced challenges in defining their new role but
welcomed the slowdown in the rhythm of life and experienced overwhelming maternal
feelings. CONCLUSION: Our findings suggest that postnatal quality of life is a
concept that changes over time and differs between countries.
PMID- 29937372
TI - Mitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling.
AB - Mitochondrial respiratory supercomplexes, comprising complexes I, III, and IV,
are the minimal functional units of the electron transport chain. Assembling the
individual complexes into supercomplexes may stabilize them, provide greater
spatiotemporal control of respiration, or, controversially, confer kinetic
advantages through the sequestration of local quinone and cytochrome c pools
(substrate channeling). Here, we have incorporated an alternative quinol oxidase
(AOX) into mammalian heart mitochondrial membranes to introduce a competing
pathway for quinol oxidation and test for channeling. AOX substantially increases
the rate of NADH oxidation by O2 without affecting the membrane integrity, the
supercomplexes, or NADH-linked oxidative phosphorylation. Therefore, the quinol
generated in supercomplexes by complex I is reoxidized more rapidly outside the
supercomplex by AOX than inside the supercomplex by complex III. Our results
demonstrate that quinone and quinol diffuse freely in and out of supercomplexes:
substrate channeling does not occur and is not required to support respiration.
PMID- 29937373
TI - Deconstructing Adipogenesis Induced by beta3-Adrenergic Receptor Activation with
Single-Cell Expression Profiling.
AB - Recruitment of brown/beige adipocytes (BAs) in white adipose tissue (WAT)
involves proliferation and differentiation of adipocyte stem cells (ASCs) in
concert with close interactions with resident immune cells. To deconvolve stromal
cell heterogeneity in a comprehensive and unbiased fashion, we performed single
cell RNA sequencing (scRNA-seq) of >33,000 stromal/vascular cells from epididymal
WAT (eWAT) and inguinal WAT (iWAT) under control conditions and during beta3
adrenergic receptor (ADRB3) activation. scRNA-seq identified distinct ASC
subpopulations in eWAT and iWAT that appeared to be differentially poised to
enter the adipogenic pathway. ADRB3 activation triggered the dramatic appearance
of proliferating ASCs in eWAT, whose differentiation into BAs could be inferred
from a single time point. scRNA-seq identified various immune cell types in eWAT,
including a proliferating macrophage subpopulation that occupies adipogenic
niches. These results demonstrate the power of scRNA-seq to deconstruct
adipogenic niches and suggest novel functional interactions among resident
stromal cell subpopulations.
PMID- 29937374
TI - Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1.
AB - The circadian clock coordinates behavioral and circadian cues with availability
and utilization of nutrients. Proteasomal degradation of clock repressors, such
as cryptochrome (CRY)1, maintains periodicity. Whether macroautophagy, a quality
control pathway, degrades circadian proteins remains unknown. Here we show that
circadian proteins BMAL1, CLOCK, REV-ERBalpha, and CRY1 are lysosomal targets,
and that macroautophagy affects the circadian clock by selectively degrading
CRY1. Autophagic degradation of CRY1, an inhibitor of gluconeogenesis, occurs in
a diurnal window when rodents rely on gluconeogenesis, suggesting that CRY1
degradation is time-imprinted to maintenance of blood glucose. High-fat feeding
accelerates autophagic CRY1 degradation and contributes to obesity-associated
hyperglycemia. CRY1 contains several light chain 3 (LC3)-interacting region (LIR)
motifs, which facilitate the interaction of cargo proteins with the autophagosome
marker LC3. Using mutational analyses, we identified two distinct LIRs on CRY1
that exert circadian glycemic control by regulating CRY1 degradation, revealing
LIRs as potential targets for controlling hyperglycemia.
PMID- 29937375
TI - Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1beta Loop to Drive Foam
Cell Formation and Accelerate Atherosclerosis.
AB - Pathogen burden accelerates atherosclerosis, but the mechanisms remain
unresolved. Activation of the NLRP3 inflammasome is linked to atherogenesis. Here
we investigated whether Chlamydia pneumoniae (C.pn) infection engages NLRP3 in
promoting atherosclerosis. C.pn potentiated hyperlipidemia-induced inflammasome
activity in cultured macrophages and in foam cells in atherosclerotic lesions of
Ldlr-/- mice. C.pn-induced acceleration of atherosclerosis was significantly
dependent on NLRP3 and caspase-1. We discovered that C.pn-induced extracellular
IL-1beta triggers a negative feedback loop to inhibit GPR109a and ABCA1
expression and cholesterol efflux, leading to accumulation of intracellular
cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in
plaque lesions in Nlrp3-/- mice in both hyperlipidemic and C.pn infection models.
Mature IL-1beta and cholesterol may compete for access to the ABCA1 transporter
to be exported from macrophages. C.pn exploits this metabolic-immune crosstalk,
which can be modulated by NLRP3 inhibitors to alleviate atherosclerosis.
PMID- 29937376
TI - Acute and Repeated Treatment with 5-PAHSA or 9-PAHSA Isomers Does Not Improve
Glucose Control in Mice.
AB - Fatty acid esters of hydroxylated fatty acids (FAHFAs) were discovered as a novel
class of endogenous mammalian lipids whose profound effects on metabolism have
been shown. In the current study, in vitro and in vivo the metabolic effects of
two of these FAHFAs, namely palmitic acid-5- (or -9) -hydroxy-stearic acid (5- or
9-PAHSA, respectively) were profiled. In DIO mice fed with differentially
composed low- or high-fat diets, acute and subchronic treatment with 5-PAHSA and
9-PAHSA alone, or in combination, did not significantly improve the deranged
metabolic status. Neither racemic 5- or 9-PAHSA, nor the enantiomers were able
to: (1) increase basal or insulin-stimulated glucose uptake in vitro, (2)
stimulate GLP-1 release from GLUTag cells, or (3) induce GSIS in rat, mouse, or
human islets or in a human pancreatic beta cell line. Therefore, our data do not
support the further development of PAHSAs or their derivatives for the control of
insulin resistance and hyperglycemia.
PMID- 29937377
TI - The Drosophila Immune Deficiency Pathway Modulates Enteroendocrine Function and
Host Metabolism.
AB - Enteroendocrine cells (EEs) are interspersed between enterocytes and stem cells
in the Drosophila intestinal epithelium. Like enterocytes, EEs express components
of the immune deficiency (IMD) innate immune pathway, which activates
transcription of genes encoding antimicrobial peptides. The discovery of large
lipid droplets in intestines of IMD pathway mutants prompted us to investigate
the role of the IMD pathway in the host metabolic response to its intestinal
microbiota. Here we provide evidence that the short-chain fatty acid acetate is a
microbial metabolic signal that activates signaling through the enteroendocrine
IMD pathway in a PGRP-LC-dependent manner. This, in turn, increases transcription
of the gene encoding the endocrine peptide Tachykinin (Tk), which is essential
for timely larval development and optimal lipid metabolism and insulin signaling.
Our findings suggest innate immune pathways not only provide the first line of
defense against infection but also afford the intestinal microbiota control over
host development and metabolism.
PMID- 29937379
TI - Saving PHACE.
PMID- 29937378
TI - Evidence for a Non-leptin System that Defends against Weight Gain in Overfeeding.
AB - Weight is defended so that increases or decreases in body mass elicit responses
that favor restoration of one's previous weight. While much is known about the
signals that respond to weight loss and the central role that leptin plays, the
lack of experimental systems studying the overfed state has meant little is known
about pathways defending against weight gain. We developed a system to study this
physiology and found that overfed mice defend against increased weight gain with
graded anorexia but, unlike weight loss, this response is independent of
circulating leptin concentration. In overfed mice that are unresponsive to
orexigenic stimuli, adipose tissue is transcriptionally and immunologically
distinct from fat of ad libitum-fed obese animals. These findings provide
evidence that overfeeding-induced obesity alters adipose tissue and central
responses in ways that are distinct from ad libitum obesity and activates a non
leptin system to defend against weight gain.
PMID- 29937380
TI - Evaluation of differences in injury patterns according to seat position in trauma
victims survived traffic accidents.
AB - PURPOSE: Investigation of injury patterns epidemiology among car occupants may
help to develop different therapeutic approach according to the seat position.
The aim of the study was to evaluate and compare differences in the incidence of
serious injuries, between occupants in different locations in private cars.
METHODS: A retrospective study including trauma patients who were involved in
motor vehicle accidents and admitted alive to 20 hospitals (6 level I trauma
centers and 14 level II trauma centers). We examined the incidence of injures
with abbreviated injury score 3 and more, and compared their occurrence between
seat locations. RESULTS: The study included 28,653 trauma patients, drivers
account for 60.8% (17,417). Front passenger mortality was 0.47% higher than in
drivers. Rear seat passengers were at greater risk (10.26%) for traumatic brain
injuries than front seat passengers (7.48%) and drivers (7.01%). Drivers are less
likely to suffer from serious abdominal injuries (3.84%) compared to the
passengers (front passengers - 5.91%, rear passengers - 5.46%). CONCLUSION: Out
of victims who arrived alive to the hospital, highest mortality was found in
front seat passengers. The rate of serious chest injuries was higher as well.
Rear seat passengers are at greater risk for serious traumatic brain injuries.
All passengers have a greater incidence of abdominal injuries. These findings
need to be addressed in order to develop "customized" therapeutic policy in
trauma victims.
PMID- 29937381
TI - Treatment of critical hand ischemia via orbital atherectomy and focal force
balloon angioplasty: A mini-review.
AB - Calcified lesions in below-the-elbow (BTE) arteries are common in patients with
diabetes or end-stage renal disease and can lead to critical hand ischemia (CHI).
Treatment of calcified lesions with atherectomy has proved useful in the lower
extremities, however, atherectomy in the upper extremities and especially BTE, is
not typically considered due to the small vessel size. We review and discuss
these studies along with other CHI-related articles and also present a case of a
severely calcified ulnar artery lesion treated with orbital atherectomy and plain
Chocolate balloon angioplasty.
PMID- 29937382
TI - Iatrogenic atrial septal defect post mitral valve in valve implantation.
AB - A 75 year-old female with symptomatic severe mitral regurgitation of a bio
prosthetic valve secondary to valve leaflet perforation due to endocarditis
underwent a mitral valve in valve replacement in an existing Hancock 27 mm valve
using a trans-femoral/trans-septal approach. The procedure was complicated by an
iatrogenic atrial septal defect post trans-septal puncture causing a severe right
to-left shunt due, possibly, to the combination of severe pulmonary hypertension
and moderate tricuspid regurgitation the patient had suffered from at base line.
Once the sheath was removed an immediate desaturation was observed which required
emergent closure with an AMPLATZER ASD Occluder device (St. Jude Medical/Abbott
Structural, St. Paul, Minnesota, MN). This stabilized the patient and returned
her blood oxygen levels to normal. The case brings forth a rare but important
complication that may occur during trans-septal procedures especially when using
large sheaths. It emphasizes the importance of proper echocardiographic and
hemodynamic evaluation prior to such procedures in order to be prepared for such
complications.
PMID- 29937383
TI - Same versus next day discharge after elective transradial PCI: The RAdial SAme
Day DischArge after PCI trial. (The RASADDA-PCI trial).
AB - BACKGROUND AND PURPOSE: Transradial percutaneous coronary intervention (TR-PCI)
has been increasingly popular over the last decade in the US. Previous studies
have shown that same-day (SD) discharge after elective PCI is as safe as
overnight (ON) observation. Our study was performed to assess the clinical and
financial impact of early discharge in patients undergoing TR-PCI. METHODS: This
is a single center registry of patients undergoing elective TR-PCI. Timing of
discharge was determined by the treating physician. (Groups: Same Day Discharge
SD-; Overnight Stay -ON-). Demographic data, procedural characteristics and
adverse outcomes were recorded. Outcomes included 30 day-MACE and procedure-
related complications, as well as total operative costs in patients from both
groups. Propensity score matching for patient demographics, coronary symptoms and
procedure indicators was used to compare both groups. RESULTS: The entire cohort
included 852 patients (429 in SD group and 423 in ON group) and the propensity
score matched groups of 245 patients in the SD group and 245 patients in the ON
group. The two groups had no significant baseline clinical differences, and had
similar clinical outcomes. Specifically, no significant difference was noted in
procedural complications (3.7% vs 2.5%, p = 0.43), re-hospitalization (4.1% vs
4.1%, p = 0.92), re-intervention (2.5% vs 2.1%, p = 0.77), myocardial infarction
(0% vs 0.08%, p = 0.15), stroke (0% vs 0%, p = 1.0) and all-cause mortality (0%
vs 0%, p = 1.0). SD Group patients had a significant lower procedure-related cost
compared to overnight stay patients ($3,346.45 vs $4,681.99, p < 0.0001) and
lower 30-day post procedure-associated cumulative costs/total operating costs
($4,493.22 vs $7,112.21, p < 0.0001). CONCLUSION: In elective patients undergoing
low risk TR-PCI, same-day discharge seems to be a safe and feasible clinical
practice, with significant potential savings to the US healthcare system.
PMID- 29937384
TI - Recurrent Pericardial Effusion While Receiving Nivolumab for Metastatic Lung
Adenocarcinoma: Case Report and Review of the Literature.
PMID- 29937385
TI - Ventana ALK (D5F3) in the Detection of Patients Affected by Anaplastic Lymphoma
Kinase-positive Non-Small-cell Lung Cancer: Clinical and Budget Effect.
AB - BACKGROUND: To ensure identification of anaplastic lymphoma kinase-positive
(ALK+) patients, the Italian Drug Agency suggested a testing algorithm based on
the use of fluorescence in situ hybridization (FISH) and/or immunohistochemistry.
The aim was to evaluate the clinical and economic effects of adopting an
immunohistochemical test (Ventana ALK D5F3) as an option for detecting ALK
protein expression in advanced non-small cell lung cancer (NSCLC) patients.
MATERIALS AND METHODS: A budget impact model was developed by adopting the
Italian National Health Service (NHS) perspective and a 5-year period to compare
2 scenarios: the current use of D5F3 (28%; current scenario) and increased use of
D5F3 (60%; alternative scenario). The testing cost and the number and cost of the
identified ALK+ patients were evaluated. RESULTS: A more extensive use of D5F3 in
the alternative scenario showed a decrease in diagnostic costs of ~?468,000
compared with current scenario when considering all advanced NSCLC patients. If
these savings were allocated to test more NSCLC patients (75% vs. 53%), an
incremental cost per identified ALK+ patient of ?63 would be required, leading to
an overall survival gain for the alternative scenario compared with the current
scenario (32.4 vs. 27.1 months; relative increase, 20%). CONCLUSION: The use of
D5F3 would provide a cost savings for the NHS owing to a lower acquisition cost
than FISH and a comparable detection rate. The savings could be reinvested to
test a greater number of patients, leading to more efficient identification, use
of targeted therapy, and improvement in clinical outcomes of ALK+ patients.
PMID- 29937386
TI - Screening Patterns and Mortality Differences in Patients With Lung Cancer at an
Urban Underserved Community.
AB - BACKGROUND: The landmark National Lung Screening Trial demonstrated significant
reduction in lung cancer-related mortality. However, European lung cancer
screening (LCS) trials have not confirmed such benefit. We examined LCS patterns
and determined the impact of LCS-led diagnosis on the mortality of newly
diagnosed patients with lung cancer in an underserved community. PATIENTS AND
METHODS: Medical records of patients diagnosed with primary lung cancer in 2013
through 2016 (n = 855) were reviewed for primary care provider (PCP) status and
LCS eligibility and completion, determined using United States Preventative
Services Task Force guidelines. Univariate analyses of patient characteristics
were conducted between LCS-eligible patients based on screening completion.
Survival analyses were conducted using Kaplan-Meier and multivariate Cox
regression. RESULTS: In 2013 through 2016, 175 patients with primary lung cancer
had an established PCP and were eligible for LCS. Among them, 19% (33/175)
completed screening prior to diagnosis. LCS completion was associated with
younger age (P = .02), active smoking status (P < .01), earlier stage at time of
diagnosis (P < .01), follow-up in-network cancer treatment (P = .03), and
surgical management (P < .01). LCS-eligible patients who underwent screening had
improved all-cause mortality compared with those not screened (P < .01).
Multivariate regression showed surgery (hazard ratio, 0.31; P = .04)
significantly affected mortality. CONCLUSION: To our knowledge, this is the first
study to assess LCS patterns and mortality differences on patients with screen
detected lung cancer in an urban underserved setting since the inception of
United States Preventative Services Task Force guidelines. Patients with a LCS
led diagnosis had improved mortality, likely owing to cancer detection at earlier
stages with curative treatment, which echoes the finding of prospective trials.
PMID- 29937387
TI - CLASP Suppresses Microtubule Catastrophes through a Single TOG Domain.
AB - The dynamic instability of microtubules plays a key role in controlling their
organization and function, but the cellular mechanisms regulating this process
are poorly understood. Here, we show that cytoplasmic linker-associated proteins
(CLASPs) suppress transitions from microtubule growth to shortening, termed
catastrophes, including those induced by microtubule-destabilizing agents and
physical barriers. Mammalian CLASPs encompass three TOG-like domains, TOG1, TOG2,
and TOG3, none of which bind to free tubulin. TOG2 is essential for catastrophe
suppression, whereas TOG3 mildly enhances rescues but cannot suppress
catastrophes. These functions are inhibited by the C-terminal domain of CLASP2,
while the TOG1 domain can release this auto-inhibition. TOG2 fused to a
positively charged microtubule-binding peptide autonomously accumulates at
growing but not shrinking ends, suppresses catastrophes, and stimulates rescues.
CLASPs suppress catastrophes by stabilizing growing microtubule ends, including
incomplete ones, preventing their depolymerization and promoting their recovery
into complete tubes. TOG2 domain is the key determinant of these activities.
PMID- 29937388
TI - Local Arrangement of Fibronectin by Myofibroblasts Governs Peripheral Nuclear
Positioning in Muscle Cells.
AB - Skeletal muscle cells (myofibers) are rod-shaped multinucleated cells surrounded
by an extracellular matrix (ECM) basal lamina. In contrast to other cell types,
nuclei in myofibers are positioned just below the plasma membrane at the cell
periphery. Peripheral nuclear positioning occurs during myogenesis and is driven
by myofibril crosslinking and contraction. Here we show that peripheral nuclear
positioning is triggered by local accumulation of fibronectin secreted by
myofibroblasts. We demonstrate that fibronectin via alpha5-integrin mediates
peripheral nuclear positioning dependent on FAK and Src activation. Finally, we
show that Cdc42, downstream of restricted fibronectin activation, is required for
myofibril crosslinking but not myofibril contraction. Thus we identify that local
activation of integrin by fibronectin secreted by myofibroblasts activates
peripheral nuclear positioning in skeletal myofibers.
PMID- 29937390
TI - Pro-inflammatory capacity of Escherichia coli O104:H4 outbreak strain during
colonization of intestinal epithelial cells from human and cattle.
AB - In 2011, Germany was struck by the largest outbreak of hemolytic uremic syndrome.
The highly virulent E. coli O104:H4 outbreak strain LB226692 possesses a blended
virulence profile combining genetic patterns of human adapted enteroaggregative
E. coli (EAEC), rarely detected in animal hosts before, and enterohemorrhagic E.
coli (EHEC), a subpopulation of Shiga toxin (Stx)-producing E. coli (STEC)
basically adapted to the ruminant host. This study aimed at appraising the
relative level of adaptation of the EAEC/EHEC hybrid strain LB226692 to humans
and cattle. Adherence and invasion of the hybrid strain to intestinal (jejunal
and colonic) epithelial cells (IEC) of human and bovine origin was compared to
that of E. coli strains representative of different pathovars and commensal E.
coli by means of light and electron microscopy and culture. Strain-specific host
gene transcription profiles of selected cytokines and chemokines as well as host
induced transcription of bacterial virulence genes were assessed. The release of
Stx upon host cell contact was quantified. The outbreak strain's immunomodulation
was assessed by cultivating primary bovine macrophages with conditioned
supernatants from IEC infection studies with E. coli, serving as model for the
innate immunity of the bovine gut. The outbreak strain adhered to IEC of both,
human and bovine origin. Electron microscopy of infected cells revealed the
strain's particular affinity to human small IEC, in contrast to few interactions
with bovine small IEC. The outbreak strain possessed a high-level of adhesive
power, similar to human-associated E. coli strains and in contrast to bovine
associated STEC strains. The outbreak strain displayed a non-invasive phenotype,
in contrast to some bovine-associated E. coli strains, which were invasive. The
outbreak strain provoked some pro-inflammatory activity in human cells, but to a
lower extent as compared to other pathotypes. In contrasts to bovine-associated
E. coli strains, the outbreak strain induced marked pro-inflammatory activity
when interacting with bovine host cells directly (IEC) and indirectly
(macrophages). Among stx2-positive strains, the human-pathogenic strains
(LB226692 and EHEC strain 86-24) released higher amounts of Stx compared to
bovine-associated STEC. The findings imply that the outbreak strain is rather
adapted to humans than to cattle. However, the outbreak strain's potential to
colonize IEC of both host species and the rather mixed reaction patterns observed
for all strains under study indicate, that even STEC strains with an unusual
genotype as the EHEC O104:H4 outbreak strain, i.e. with an EAEC genetic
background, may be able to conquer other reservoir hosts.
PMID- 29937391
TI - Lysogenic conversion of atypical enteropathogenic Escherichia coli (aEPEC) from
human, murine, and bovine origin with bacteriophage Phi3538 Deltastx2::cat proves
their enterohemorrhagic E. coli (EHEC) progeny.
AB - Bacteriophages play an important role in the evolution of bacterial pathogens. A
phage-mediated transfer of stx-genes to atypical enteropathogenic E. coli (aEPEC)
which are prevalent in different hosts, would convert them to enterohemorrhagic
E. coli (EHEC). We decided to confirm this hypothesis experimentally to provide
conclusive evidence that aEPEC isolated from different mammalian hosts are indeed
progenitors of typical EHEC which gain the ability to produce Shiga-Toxin by
lysogeny with stx-converting bacteriophages, utilizing the model phage Phi3538
Deltastx2::cat. We applied a modified in vitro plaque-assay, using a high titer
of a bacteriophage carrying a deletion in the stx2 gene (Phi3538 Deltastx2::cat)
to increase the detection of lysogenic conversion events. Three wild-type aEPEC
strains were chosen as acceptor strains: the murine aEPEC-strain IMT14505
(sequence type (ST)28, serotype Ont:H6), isolated from a striped field mouse
(Apodemus agrarius) in the surrounding of a cattle shed, and the human aEPEC
strain 910#00 (ST28, Ont:H6). The close genomic relationship of both strains
implies a high zoonotic potential. A third strain, the bovine aEPEC IMT19981, was
of serotype O26:H11 and ST21 (STC29). All three aEPEC were successfully
lysogenized with phage Phi3538 Deltastx2::cat. Integration of the bacteriophage
DNA into the aEPEC host genomes was confirmed by amplification of chloramphenicol
transferase (cat) marker gene and by Southern-Blot hybridization. Analysis of the
whole genome sequence of each of the three lysogens showed that the bacteriophage
was integrated into the known tRNA integration site argW, which is highly
variable among E. coli. In conclusion, the successful lysogenic conversion of
aEPEC with a stx-phage in vitro underlines the important role of aEPEC as
progenitors of EHEC. Given the high prevalence and the wide host range of aEPEC
acceptors, their high risk of zoonotic transmission should be recognized in
infection control measures.
PMID- 29937389
TI - Membrane Flow Drives an Adhesion-Independent Amoeboid Cell Migration Mode.
AB - Cells migrate by applying rearward forces against extracellular media. It is
unclear how this is achieved in amoeboid migration, which lacks adhesions typical
of lamellipodia-driven mesenchymal migration. To address this question, we
developed optogenetically controlled models of lamellipodia-driven and amoeboid
migration. On a two-dimensional surface, migration speeds in both modes were
similar. However, when suspended in liquid, only amoeboid cells exhibited rapid
migration accompanied by rearward membrane flow. These cells exhibited increased
endocytosis at the back and membrane trafficking from back to front. Genetic or
pharmacological perturbation of this polarized trafficking inhibited migration.
The ratio of cell migration and membrane flow speeds matched the predicted value
from a model where viscous forces tangential to the cell-liquid interface propel
the cell forward. Since this mechanism does not require specific molecular
interactions with the surrounding medium, it can facilitate amoeboid migration
observed in diverse microenvironments during immune function and cancer
metastasis.
PMID- 29937392
TI - Chelating and antioxidant properties of l-Dopa containing tetrapeptide for the
treatment of neurodegenerative diseases.
AB - Neurodegenerative diseases share a common pathogenetic mechanism involving
aggregation and deposition of misfolded proteins, oxidative stress, metal
dyshomeostasis, and glutamate exicitotoxicity, which lead to progressive
dysfunction of central nervous system (CNS). A potential strategy to counteract
these deleterious events at neuronal level is represented by the employment of a
novel class of multi-target therapeutic agents that selectively and
simultaneously hit these targets In this paper, we report the metal binding and
antioxidant properties of a novel metal-protein attenuating peptide, GSH-LD, a
tetrapeptide obtained by linking glutathione, a well-known antioxidant
tripeptide, to L-Dopa. Results demonstrated that GSH-LD possesses chelating
capabilities in order to selectively target the excess of metals without
interfere with metal-containing antioxidant enzymes. Moreover, antioxidant assays
revealed a large contribution of GSH-LD to restore the antioxidant defences of
damaged neuronal cells.
PMID- 29937393
TI - Urologists reduce overtreatment in prostate cancer.
PMID- 29937394
TI - New genetic discoveries in prostate cancer.
PMID- 29937395
TI - Outcome feedback technology helps therapists to tailor care.
PMID- 29937396
TI - Feedback-informed treatment versus usual psychological treatment for depression
and anxiety: a multisite, open-label, cluster randomised controlled trial.
AB - BACKGROUND: Previous research suggests that the use of outcome feedback
technology can enable psychological therapists to identify and resolve obstacles
to clinical improvement. We aimed to assess the effectiveness of an outcome
feedback quality assurance system applied in stepped care psychological services.
METHODS: This multisite, open-label, cluster randomised controlled trial was done
at eight National Health Service (NHS) Trusts in England, involving therapists
who were qualified to deliver evidence-based low-intensity or high-intensity
psychological interventions. Adult patients (18 years or older) who accessed
individual therapy with participating therapists were eligible for inclusion,
except patients who accessed group therapies and those who attended less than two
individual therapy sessions. Therapists were randomly assigned (1:1) to an
outcome feedback intervention group or a treatment-as-usual control group by use
of a computer-generated randomisation algorithm. The allocation of patients to
therapists was quasi-random, whereby patients on waiting lists were allocated
sequentially on the basis of therapist availability. All patients received low
intensity (less than eight sessions) or high-intensity (up to 20 sessions)
psychological therapies for the duration of the 1-year study period. An automated
computer algorithm alerted therapists in the outcome feedback group to patients
who were not on track, and primed them to review these patients in clinical
supervision. The primary outcome was symptom severity on validated depression
(Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalised Anxiety
Disorder-7 [GAD-7]) measures after treatment of varying durations, which were
compared between groups with multilevel modelling, controlling for cluster
(therapist) effects. We used an intention-to-treat approach. This trial was
prospectively registered with ISRCTN, number ISRCTN12459454. FINDINGS: In total,
79 therapists were recruited to the study between Jan 8, 2016, and July 15, 2016,
but two did not participate. Of these participants, 39 (51%) were randomly
assigned to the outcome feedback group and 38 (49%) to the control group.
Overall, 2233 patients were included in the trial (1176 [53%] were treated by
therapists in the outcome feedback group, and 1057 [47%] by therapists in the
control group). Patients classified as not on track had less severe symptoms
after treatment if they were allocated to the outcome feedback group than those
in the control group (PHQ-9 d=0.23, B=-1.03 [95% CI -1.84 to -0.23], p=0.012; GAD
7 d=0.19, B=-0.85 [-1.56 to -0.14], p=0.019). INTERPRETATION: Supplementing
psychological therapy with low-cost feedback technology can reduce symptom
severity in patients at risk of poor response to treatment. This evidence
supports the implementation of outcome feedback in stepped care psychological
services. FUNDING: English NHS and Department of Health Sciences, University of
York, York, UK.
PMID- 29937397
TI - When grief has mates: King Lear and the politics of happiness.
PMID- 29937398
TI - Immune-mediated acquired lecithin-cholesterol acyltransferase deficiency: A case
report and literature review.
AB - BACKGROUND: Recessive inherited disorder lecithin-cholesterol acyltransferase
(LCAT) deficiency causes severe hypocholesterolemia and nephrotic syndrome.
Characteristic lipoprotein subfractions have been observed in familial LCAT
deficiency (FLD) with renal damage. OBJECTIVE: We described a case of acquired
LCAT deficiencies with literature review. METHODS: The lipoprotein profiles
examined by gel permeation-high-performance liquid chromatography (GP-HPLC) and
native 2-dimensional electrophoresis before and after prednisolone (PSL)
treatment. RESULTS: Here we describe the case of a 67-year-old man with severely
low levels of cholesterol. The serum LCAT activity was undetectable, and
autoantibodies against it were detected. The patient developed nephrotic syndrome
at the age of 70 years. Renal biopsy revealed not only membranous
glomerulonephritis but also lesions similar to those seen in FLD. We initiated
PSL treatment, which resulted in remission of the nephrotic syndrome. In GP-HPLC
analysis, lipoprotein profile was similar to that of FLD although lipoprotein X
level was low. Acquired LCAT deficiencies are extremely rare with only 7 known
cases including ours. Patients with undetectable LCAT activity levels develop
nephrotic syndrome that requires PSL treatment; cases whose LCAT activity levels
can be determined may also develop nephrotic syndrome, but spontaneously recover.
CONCLUSION: Lipoprotein X may play a role in the development of renal impairment
in individuals with FLD. However, the effect might be less significant in
individuals with acquired LCAT deficiency.
PMID- 29937399
TI - Feasibility and Efficacy of High-Dose Chemotherapy and Autologous Hematopoietic
Cell Transplantation for HIV-Associated Lymphoma: A Single-Institution
Experience.
AB - BACKGROUND: HIV-associated lymphomas (HAL) remain an important cause of morbidity
and mortality in HIV patients, especially in the setting of treatment-refractory
disease. Hematopoietic cell transplantation (HCT) is considered a curative option
for patients with refractory HAL. PATIENTS AND METHODS: We report the efficacy of
autologous HCT in 20 patients with HAL [non-Hodgkin lymphoma = 14 (70%), Hodgkin
lymphoma = 6 (30%)]. At the time of transplantation, the median peripheral blood
CD4+ count was 226 cells/MUL. HIV virus load was undetectable in 14 (70%) of 20
patients. RESULTS: The median follow-up of surviving patients was 47 months
(range, 20-119 months). The median time to neutrophil engraftment was 11 days.
The median progression-free survival and median overall survival have not been
reached. At 4 years after transplantation, progression-free survival and overall
survival were 65% and 70%, respectively. Six patients died from disease relapse
or progression (n = 5) and infection (n = 1). Nonrelapse mortality was 0 and 5%
at 100 days and 4 years after transplantation, respectively. CONCLUSION:
Autologous HCT is an effective therapy for refractory/relapsed HAL with
manageable toxicity, similar to non-HIV patients.
PMID- 29937400
TI - Clinical Outcomes With Ring Sideroblasts and SF3B1 Mutations in Myelodysplastic
Syndromes: MDS Clinical Research Consortium Analysis.
AB - BACKGROUND: Recurrent somatic mutations in SF3B1 have been identified in patients
with myelodysplastic syndromes (MDS) and are associated with ring sideroblasts
(RS) and relatively favorable clinical outcomes. The 2016 World Health
Organization classification categorizes patients with >= 5% RS and SF3B1 mutation
as MDS-RS, in contrast to its prior MDS-RS classification (>= 15% RS, no
genotyping data). Treatment responses in MDS patients with mutated SF3B1 are not
well described. PATIENTS AND METHODS: Patients with MDS and known SF3B1
mutational status were identified from MDS Clinical Research Consortium
institutions and grouped when possible as 5% to 15% or >= 15% RS. Patients with
wild-type versus mutated SF3B1 were matched 2:1 to analyze treatment response.
RESULTS: Of 471 patients identified, 16% showed SF3B1 mutation. More patients
with mutated SF3B1 were lower-risk MDS. We found that 50% were RS-positive
compared to 19% of wild-type patients (P < .001). Having the mutation was
associated with better overall survival (hazard ratio = 0.48, P = .001) and
longer leukemia-free survival (hazard ratio = 0.5, P < .005). Patients with RS
and the mutation had the best outcome. Regarding treatment response, 14 (35%) of
40 erythroid-stimulating agent-treated patients with mutation experienced
response versus 9 (16%) of 56 wild-type patients (P = .032), with no differences
in response to hypomethylating agents or lenalidomide. CONCLUSION: SF3B1
mutations in MDS are commonly associated with RS and show better outcomes, with
mutated/positive RS presence being significantly better than isolated RS or
presence of mutation or neither. Patients with mutation showed better responses
to an erythroid-stimulating agent. A new categorization incorporating SF3B1
mutation status, regardless of RS percentage, shows clinical value.
PMID- 29937401
TI - HDAC6 at Crossroads of Infection and Innate Immunity.
AB - Histone deacetylase 6 (HDAC6) acts by enzyme-dependent and -independent
mechanisms to regulate diverse cellular processes including autophagy, the
ubiquitin proteasome system, and cell migration. HDAC6 also has emerging roles in
innate immunity, including pathogen sensing and destruction, thus placing this
enzyme at the crossroads of infection and innate immunity.
PMID- 29937402
TI - Adverse birth outcomes in relation to maternal marital and cohabitation status in
Canada.
AB - PURPOSE: An increasing percentage of children are born to couples who cohabit but
are not legally married. Using data from a nationally representative Canadian
sample, we estimated associations of maternal marital and cohabitation status
with stillbirth, infant mortality, preterm birth (PTB), and small- and large-for
gestational-age (SGA and LGA) birth. METHODS: The 2006 Canadian Birth-Census
Cohort was created by linking birth registration data with the 2006 long-form
census. We used log-binomial regression to estimate risk ratios (RRs) for adverse
birth outcomes associated with being single or living with a common-law partner.
Analyses were adjusted for maternal age and education. RESULTS: Data were
analyzed for 130,931 singleton births. Adjusted RRs (95% confidence intervals)
for single mothers compared with married mothers were 1.92 (1.51-2.42) for
stillbirth, 2.08 (1.55-2.81) for infant mortality, 1.36 (1.27-1.46) for PTB, 1.31
(1.22-1.39) for SGA birth, and 0.95 (0.90-1.01) for LGA birth. Adjusted RRs for
cohabiting mothers compared with married mothers were 0.93 (0.74-1.16) for
stillbirth, 1.05 (0.81-1.35) for infant mortality, 1.09 (1.03-1.15) for PTB, 1.05
(0.99-1.10) for SGA birth, and 0.96 (0.92-1.00) for LGA birth. CONCLUSIONS: In a
nationally representative Canadian birth cohort, cohabiting and legally married
women experienced similar birth outcomes, but most outcomes for single women were
substantially worse.
PMID- 29937403
TI - Patterns of cleaning product exposures using a novel clustering approach for data
with correlated variables.
AB - PURPOSE: Clustering methods may be useful in epidemiology to better characterize
exposures and account for their multidimensional aspects. In this context,
application of clustering models allowing for highly dependent variables is of
particular interest. We aimed to characterize patterns of domestic exposure to
cleaning products using a novel clustering model allowing for highly dependent
variables. METHODS: To identify domestic cleaning patterns in a large population
of French women, we used a mixture model of dependency blocks. This novel
approach specifically models within-class dependencies, and is an alternative to
the latent class model, which assumes conditional independence. Analyses were
conducted in 19,398 participants of the E3N study (women aged 61-88 years) who
completed a questionnaire regarding household cleaning habits. RESULTS: Seven
classes were identified, which differed with the frequency of cleaning tasks
(e.g., dusting/sweeping/hoovering) and use of specific products (e.g., bleach,
sprays). The model also grouped the variables into conditionally independent
blocks, providing a summary of the main dependencies among the variables.
CONCLUSIONS: The mixture model of dependency blocks, a useful alternative to the
latent class model, may have broader application in epidemiology, in particular,
in the context of exposome research and growing need for data-reduction methods.
PMID- 29937404
TI - A high anticholinergic burden is associated with a history of falls in the
previous year in middle-aged women: findings from the Aberdeen Prospective
Osteoporosis Screening Study.
AB - PURPOSE: To examine the cross-sectional association between anticholinergic
medication burden (ACB) and a history of falls, bone mineral density, and low
trauma fractures in middle-aged women aged under 65 years from the Aberdeen
Prospective Osteoporosis Screening Study. METHODS: ACB (0 = none, 1 = possible,
>=2 = definite) was calculated from medication use for 3883 Caucasian women [mean
age (SD) = 54.3 (2.3) years] attending the second Aberdeen Prospective
Osteoporosis Screening Study visit (1997-2000). Outcomes were examined using
logistic regression. Model adjustments were selected a priori based on expert
opinion. RESULTS: Of 3883 participants, 3293 scored ACB = 0, 328 scored ACB = 1,
and 262 scored ACB >=2. High ACB burden (>=2) was associated with increased odds
(ACB = 0 reference) for falls (fully adjusted odds ratio [95% confidence
intervals] = 1.81 [1.25-2.62]; P = 0.002) and having low bone mineral density
(lowest quintile-20%) at Ward's triangle (3.22 [1.30-7.99]; P = 0.01). A history
of falls over the year prior to the study visit in participants with ACB score
>=2 was 32 per 100. For ACB categories 1 and 0, a history of falls per 100 was 21
and 22, respectively. CONCLUSIONS: The risk of falling associated with ACB
observed in older age may also extend to middle-aged women.
PMID- 29937405
TI - Resistance to Enediyne Antitumor Antibiotics by Sequestration.
AB - The enediynes, microbial natural products with extraordinary cytotoxicities, have
been translated into clinical drugs. Two self-resistance mechanisms are known in
the enediyne producers-apoproteins for the nine-membered enediynes and self
sacrifice proteins for the ten-membered enediyne calicheamicin. Here we show
that: (1) tnmS1, tnmS2, and tnmS3 encode tiancimycin (TNM) resistance in its
producer Streptomyces sp. CB03234, (2) tnmS1, tnmS2, and tnmS3 homologs are found
in all anthraquinone-fused enediyne producers, (3) TnmS1, TnmS2, and TnmS3 share
a similar beta barrel-like structure, bind TNMs with nanomolar KD values, and
confer resistance by sequestration, and (4) TnmS1, TnmS2, and TnmS3 homologs are
widespread in nature, including in the human microbiome. These findings unveil an
unprecedented resistance mechanism for the enediynes. Mechanisms of self
resistance in producers serve as models to predict and combat future drug
resistance in clinical settings. Enediyne-based chemotherapies should now
consider the fact that the human microbiome harbors genes encoding enediyne
resistance.
PMID- 29937406
TI - Inhibition of Flaviviruses by Targeting a Conserved Pocket on the Viral Envelope
Protein.
AB - Viral envelope proteins are required for productive viral entry and initiation of
infection. Although the humoral immune system provides ample evidence for
targeting envelope proteins as an antiviral strategy, there are few
pharmacological interventions that have this mode of action. In contrast to
classical antiviral targets such as viral proteases and polymerases, viral
envelope proteins as a class do not have a well-conserved active site that can be
rationally targeted with small molecules. We previously identified compounds that
inhibit dengue virus by binding to its envelope protein, E. Here, we show that
these small molecules inhibit dengue virus fusion and map the binding site of
these compounds to a specific pocket on E. We further demonstrate inhibition of
Zika, West Nile, and Japanese encephalitis viruses by these compounds, providing
pharmacological evidence for the pocket as a target for developing broad-spectrum
antivirals against multiple, mosquito-borne flavivirus pathogens.
PMID- 29937407
TI - Genetically Encoded Protein Phosphorylation in Mammalian Cells.
AB - Protein phosphorylation regulates diverse processes in eukaryotic cells.
Strategies for installing site-specific phosphorylation in target proteins in
eukaryotic cells, through routes that are orthogonal to enzymatic post
translational modification, would provide a powerful route for defining the
consequences of particular phosphorylations. Here we show that the
SepRSv1.0/tRNAv1.0CUA pair (created from the Methanococcus maripaludis
phosphoseryl-transfer RNA synthetase [MmSepRS]/Methanococcus janaschii
[Mj]tRNAGCACys pair) is orthogonal in mammalian cells. We create a eukaryotic
elongation factor 1 alpha (EF-1alpha) variant, EF-1alpha-Sep, that enhances
phosphoserine incorporation, and combine this with a mutant of eRF1, and
manipulations of the cell's phosphoserine biosynthetic pathway, to enable the
genetically encoded incorporation of phosphoserine and its non-hydrolyzable
phosphonate analog. Using this approach we demonstrate synthetic activation of a
protein kinase in mammalian cells.
PMID- 29937408
TI - Influenza A(H1N1)pdm09 epidemiology in the Eastern Province of Saudi Arabia.
AB - OBJECTIVES: The influenza A(H1N1)pdm09 virus caused a worldwide pandemic in 2009
2010 and has since remained in seasonal circulation. This study was conducted to
determine any variations in the influenza A(H1N1)pdm09 status according to sex,
age group, sample type, or location within the Eastern Province of the Kingdom of
Saudi Arabia. METHODS: Samples from 749 patients with suspected Middle East
respiratory coronavirus who presented to Johns Hopkins Aramco Healthcare
facilities in the Eastern Province of Saudi Arabia were tested reflexively for
influenza A/H1N1 2009 by the Ministry of Health using the RealTime ready
Influenza A/H1N1 Detection Set for real-time PCR. The sample types included
nasopharyngeal swabs (n=677), expectorated deep cough sputum (n=32), induced
sputum (n=17), and tracheal aspirates (n=23). RESULTS: The incidence of influenza
A(H1N1)pdm09 was higher among younger patients; 27.94% of patients in the 0-19
year age group tested positive compared to only 3.51% of patients in the >=80
year age group. The incidence of influenza A(H1N1)pdm09 was higher in Ras Tanura
city compared to other locations in the Eastern Province. CONCLUSIONS: Younger
individuals in the Eastern Province of the Kingdom of Saudi Arabia had a
relatively higher risk of influenza A(H1N1)pdm09 infection. Additionally, an
outbreak of influenza A(H1N1)pdm09 may have occurred in Ras Tanura city between
April 2015 and February 2016.
PMID- 29937409
TI - Converging findings from linkage between periodontal pathogen with atopic and
allergic immune response.
AB - : This study aims to explore a relationship between exposures of whole-cell
Porphyromonas gingivalis in various doses with atopic inflammatory responses at
experimental mice. A pretest-posttest controlled group design, with 16 Wistar
rats (Rattus novergicus) randomized into four groups. Group 1 was the control
group. Group 2 was given low-dose (9 * 107 colony-forming unit) of P. gingivalis.
Group 3 was given medium-dose (9 * 109 colony-forming unit) of P. gingivalis.
Group 4 was given high-dose (9 * 1011 colony-forming unit) of P. gingivalis.
Interleukin-4, Interleukin-5, Interleukin-17F, Interleukin-21, Immunoglobulin-E,
Immunoglobulin-G4, and gamma-Interferon were measured by direct-sandwich ELISA
just before the treatments began, day-4, and day-11 after treatments. There is a
sudden increase of Interleukin-4 in the group 4 (23.79 +/- 0.91 pg/ml to 54.17 +/
0.79 pg/ml; p = 0.01) and slight increase of Interleukin-5 in the group 4
(207.60 +/- 11.15 pg/ml to 243.40 +/- 9.33 pg/ml; p = 0.03). No change was
observed for Interleukin-17F in all groups. Serum concentration of Immunoglobulin
E was decreased in group 2 (-10.44 +/- 8.13 pg/ml), but increased in group 4
(+1.03 +/- 4.57 pg/ml). Taken together, some cytokines are up-regulated and
others are down-regulated after exposure to whole-cell P. gingivalis. Moreover,
study of host responses during periodontal infection may offer critical key
insight that contribute to the development of atopy. CLINICAL IMPLICATIONS: We
introduced and explained the potential role of periodontal pathogen Porphyromonas
gingivalis in systemic immune responses, along with its virulence factor inside
the oral cavity. Our results consider several changes and differences of
cytokines and immunoglobulins following whole-cell Porphyromonas gingivalis
exposure. However, results of the study need to be interpreted with caution due
to its limitations. CAPSULE SUMMARY: Interleukin (IL)-4 and IL-5 had been found
increase after exposure to the periodontal pathogens Porphyromonas gingivalis,
whereas no or minimal change had been found in the level of IL-17F, Ig-G4, and
IFN-gamma. The various cytokines and immunoglobulins shown in this study do not
prove a causal relationship, and the precise role of Porphyromonas gingivalis in
the regulation of atopic immune response warrants further investigation.
Nevertheless, these findings may provide some critical key insight into the host
responses following Porphyromonas gingivalis infection.
PMID- 29937410
TI - Adiponectin signaling and its role in bone metabolism.
AB - Adiponectin, the most prevalent adipo-cytokine in plasma plays critical metabolic
and anti-inflammatory roles is fast emerging as an important molecular target for
the treatment of metabolic disorders. Adiponectin action is critical in multiple
organs including cardio-vascular system, muscle, liver, adipose tissue, brain and
bone. Adiponectin signaling in bone has been a topic of active investigation
lately. Human association studies and multiple mice models of gene
deletion/modification failed to define a clear cause and effect of adiponectin
signaling in bone. The most plausible reason could be the multimeric forms of
adiponectin that display differential binding to receptors (adipoR1 and adipoR2)
with cell-specific receptor variants in bone. Discovery of small molecule agonist
of adipoR1 suggested a salutary role of this receptor in bone metabolism. The
downstream signaling of adipoR1 in osteoblasts involves stimulation of oxidative
phosphorylation leading to increased differentiation via the likely suppression
of wnt inhibitor, sclerostin. On the other hand, the inflammation modulatory
effect of adiponectin signaling suppresses the RANKL (receptor activator of
nuclear factor kappa-B ligand) - to - OPG (osteprotegerin) ratio in osteoblasts
leading to the suppression of osteoclastogenic response. This review will discuss
the adiponectin signaling and its role in skeletal homeostasis and critically
assess whether adipoR1 could be a therapeutic target for the treatment of
metabolic bone diseases.
PMID- 29937411
TI - Authors' Reply: Pulmonary Flow Wave Morphology Characteristics of Pulmonary
Hypertension.
PMID- 29937412
TI - Transcatheter Mitral Valve Implantation in Degenerated Bioprosthetic Valves.
AB - The use of bioprosthetic valves for mitral valve disease has been increasingly
popular with both patients and physicians, and current practice uses these valves
for increasingly younger patients. However, these valves are known to degenerate
over time. Historically, reoperation was the only recourse for a failing
bioprosthetic valve. Today, however, percutaneous options exist with the use of
transcatheter valve implantation. Determining candidacy for this less invasive
option requires careful evaluation with echocardiography. This review is focused
on the echocardiographic evaluation required pre-, intra-, and postprocedurally
during transcatheter mitral valve insertion.
PMID- 29937413
TI - Outcome of end cutaneous ureterostomy (ECU) as a non conservative option in the
management of primary obstructive megaureters (POM).
AB - INTRODUCTION: Primary obstructive megaureters (POM) can be treated with one of
the following options: conservative management with antibiotic chemoprophylaxis
and active observation of the hydroureteronephrosis (HUN) until suspicion of
renal deterioration; refluxing/non-refluxing ureteric reimplantation with
antibiotic suppression; temporary double-J stenting; endoscopic balloon
dilatation; endoureterotomy; and end cutaneous ureterostomy (ECU). OBJECTIVE: To
study the profile of patients with POM and assess the efficacy, safety and
outcome of ECU as an interim procedure. METHODS: A retrospective review was
performed of patients who underwent ECU for POM between January 2004 and December
2014. Demographics, surgical details, and outcomes were studied. RESULTS: A total
of 25 patients (19 males, six females) underwent ECU of 25 renal units for POM at
a mean age of 7 months (range 23 days to 2.5 years). Of these, nine had presented
with radiological worsening of antenatally detected HUN, 12 had symptoms
(urosepsis in nine and palpable hydronephrosis in three), three had a solitary
kidney in renal failure, and one had incidentally diagnosed renal cortical
thinning as shown in Table below. Following diversion, renal failure had resolved
in all, and febrile urinary tract infection (UTI) developed in one while awaiting
reimplantation. Undiversion was performed in 21/25 patients at a mean duration of
12 months after diversion and a mean age of 19 months. In these, the ureteric
size had decreased significantly at reimplantation. In 4/25, undiversion was not
performed due to loss of follow-up in two and a subsequent nephrectomy in two.
Two out of 21 developed febrile UTI after undiversion. The overall mean follow-up
period was 34.2 months (n = 25), while the mean follow-up after undiversion was
41.5 months (n = 21). There was no incidence of stomal complications.
CONCLUSIONS: End cutaneous ureterostomy was a safe and effective temporary
procedure for the treatment of progressive primary obstructive megaureters.
PMID- 29937414
TI - Evolutionary Ecology of Avian Malaria: Past to Present.
AB - Avian malaria is the oldest experimental system for investigating the biology and
transmission of Plasmodium parasites. Recent molecular protocols for detecting
and characterizing avian malaria lineages in the field are providing an ever
growing picture of the prevalence, distribution, host range, and diversity
hotspots of avian malaria across the world. The unparalleled genetic diversity
uncovered rivals anything that has been found in other vertebrate malarias and
seems to be matched by an equally rich phenotypic diversity, providing endless
opportunities for exploring the selective pressures under which hosts and
parasites evolve. We review the most important milestones in avian Plasmodium
research and explain why this is a unique animal model to understand the ecology
and evolution of malaria.
PMID- 29937415
TI - Achievements in colorectal cancer care during 8 years of auditing in The
Netherlands.
AB - INTRODUCTION: The efficacy of auditing is still a subject of debate and concerns
exist whether auditing promotes risk averse behaviour of physicians. This study
evaluates the achievements made in colorectal cancer surgery since the start of a
national clinical audit and assesses potential signs of risk averse behaviour.
METHODS: Data were extracted from the Dutch ColoRectal Audit (2009-2016). Trends
in outcomes were evaluated by uni and multivariable analyses. Patients were
stratified according to operative risks and changes in outcomes were expressed as
absolute (ARR) and relative risk reduction (RRR). To assess signs of risk averse
behaviour, trends in stoma construction in rectal cancer were analysed. RESULTS:
Postoperative mortality decreased from 3.4% to 1.8% in colon cancer and from 2.3%
to 1% in rectal cancer. Surgical and non-surgical complications increased, but
with less reintervention. For colon cancer, the high-risk elderly patients had
the largest ARR for complicated postoperative course (6.4%) and mortality (5.9%).
The proportion of patients receiving a diverting stoma or end colostomy after a
(L)AR decreased 11% and 7%, respectively. In low rectal cancer, patients
increasingly received a non-diverted primary anastomosis (5.4% in 2011 and 14.4%
in 2016). CONCLUSIONS: No signs of risk averse behaviour was found since the
start of the audit. Especially the high-risk elderly patients seem to have
benefitted from improvements made in colon cancer treatment in the past 8 years.
For rectal cancer, trends towards the construction of more primary anastomoses
are seen. Future quality improvement measures should focus on reducing surgical
and non-surgical complications.
PMID- 29937416
TI - Obesity as a determinant of perioperative and postoperative outcome in patients
following colorectal cancer surgery: A population-based study (2009-2016).
AB - BACKGROUND: Obesity is an increasing problem worldwide that can influence
perioperative and postoperative outcomes. However, the relationship between
obesity and treatment-related perioperative and short-term postoperative
morbidity after colorectal resections is still subject to debate. STUDY: Patients
were selected from the DCRA, a population-based audit including 83 hospitals
performing colorectal cancer (CRC) surgery. Data regarding primary resections
between 2009 and 2016 were eligible for analyses. Patients were subdivided into
six categories: underweight, normal weight, overweight and obesity class I, II
and III. RESULTS: Of 71,084 patients, 17.7% with colon and 16.4% with rectal
cancer were categorized as obese. Significant differences were found for the 30
day overall postoperative complication rate (p < 0.001), prolonged
hospitalization (p < 0.001) and readmission rate (colon cancer p < 0.005; rectal
cancer p < 0.002) in obese CRC patients. Multivariate analysis identified BMI
>=30 kg/m2 as independent predictor of a complicated postoperative course in CRC
patients. Furthermore, obesity-related comorbidities were associated with higher
postoperative morbidity, prolonged hospitalization and a higher readmission rate.
No significant differences in performance were observed in postoperative outcomes
of morbidly obese CRC patients between hospitals performing bariatric surgery and
hospitals that did not. CONCLUSION: The real-life data analysed in this study
reflect daily practice in the Netherlands and identify obesity as a significant
risk factor in CRC patients. Obesity-related comorbidities were associated with
higher postoperative morbidity, prolonged hospitalization and a higher
readmission rate in obese CRC patients. No differences were observed between
hospitals performing bariatric surgery and hospitals that did not.
PMID- 29937417
TI - Fine margin between crossed sensory and contralateral sensory loss: A case
report.
AB - The well-known sensory deficit in lateral medullary syndrome (LMS) involves
crossed ipsilateral trigeminal area and contralateral spinothalamic tract area. A
45 year old man was admitted for sudden onset slurring of speech, unsteadiness
and sensory complaints. The diagnosis was right lateral medullary syndrome due to
right Vertebral Artery occlusion. In addition to typical lateral medullary
syndromes, his sensory deficit involved contralateral half of the face, trunk and
limbs. We report this atypical sensory presentation and discuss its
neuroanatomical correlation.
PMID- 29937419
TI - Waitlist mortality and post-transplant survival in patients with cholestatic
liver disease - Impact of changes in allocation policy.
AB - BACKGROUND: This study investigated the impact of Model of end-stage liver
disease (MELD)-score introduction (MELDi) on waitlist mortality and post-liver
transplant (LT) survival in primary biliary cholangitis (PBC) and primary
sclerosing cholangitis (PSC). METHODS: LT candidates with PSC or PBC listed
between January 1983 and March 2016 were included and followed until December
2016. After MELDi in 2004, PBC patients were listed according to labMELD, PSC
patients according to the highest MELD during active cholangitis (chMELD).
RESULTS: In total, 100 PBC and 76 PSC patients were included. Waitlist mortality
in PBC was significantly higher than in PSC (16% vs. 5.3%, p = 0.031), whereas
PSC patients were significantly more often withdrawn from the waitlist due to
improved condition (3.0% vs. 13.2%, p = 0.017). Competing risks analysis
identified MELDi (HR = 4.12) and PBC (HR = 2.95) as significant predictors of
waitlist mortality. Yet, overall 10 y-patient survival increased after MELDi by
18.8% leading to a 1 y-, 5 y-, and 10 y-patient survival of 98.2%, 70.6% and
70.6% in PBC, and 83.3%, 83.3%, and 80.6% in PSC, respectively. CONCLUSIONS: PSC
patients showed significantly lower waitlist mortality irrespective of MELDi,
whereas in PBC waitlist mortality further increased after MELDi. Utility of MELD
and chMELD did not impair post LT outcome.
PMID- 29937418
TI - Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto
Extracellular Vesicles.
AB - Extracellular vesicles are promising delivery vesicles for therapeutic RNAs.
Small interfering RNA (siRNA) conjugation to cholesterol enables efficient and
reproducible loading of extracellular vesicles with the therapeutic cargo. siRNAs
are typically chemically modified to fit an application. However, siRNA chemical
modification pattern has not been specifically optimized for extracellular
vesicle-mediated delivery. Here we used cholesterol-conjugated, hydrophobically
modified asymmetric siRNAs (hsiRNAs) to evaluate the effect of backbone, 5'
phosphate, and linker chemical modifications on productive hsiRNA loading onto
extracellular vesicles. hsiRNAs with a combination of 5'-(E)-vinylphosphonate and
alternating 2'-fluoro and 2'-O-methyl backbone modifications outperformed
previously used partially modified siRNAs in extracellular vesicle-mediated
Huntingtin silencing in neurons. Between two commercially available linkers
(triethyl glycol [TEG] and 2-aminobutyl-1-3-propanediol [C7]) widely used to
attach cholesterol to siRNAs, TEG is preferred compared to C7 for productive
exosomal loading. Destabilization of the linker completely abolished silencing
activity of loaded extracellular vesicles. The loading of cholesterol-conjugated
siRNAs was saturated at ~3,000 siRNA copies per extracellular vesicle.
Overloading impaired the silencing activity of extracellular vesicles. The data
reported here provide an optimization scheme for the successful use of
hydrophobic modification as a strategy for productive loading of RNA cargo onto
extracellular vesicles.
PMID- 29937420
TI - The association between antidepressant use and orthostatic hypotension in older
people: a matched cohort study.
AB - Orthostatic hypotension (OH) is often reported as a significant potential adverse
effect of antidepressant use but the association between phasic blood pressure
(BP) and antidepressants has not yet been investigated. This cross-sectional
study compares continuously measured phasic BP and prevalence of OH in a cohort
of antidepressant users >=50 years compared with an age- and sex-matched cohort
not taking antidepressants. OH was defined as a drop in systolic BP >= 20 mm Hg
or in diastolic BP >= 10 mm Hg at 30 seconds after standing, measured using
continuous beat-to-beat finometry. Multilevel time * group interactions revealed
significantly greater systolic and diastolic BP drop in antidepressant users than
nonusers at 30 seconds after stand. The prevalence of OH among antidepressant
users was 31% (63/206), compared with 17% in nonusers (X2 = 9.7; P = .002).
Unadjusted logistic regression models demonstrated that selective serotonin
reuptake inhibitor use was associated with OH at an odds ratio of 2.11 (95%
confidence interval: 1.25-3.57); P = .005, and this association was not
attenuated when covariates including cardiac disease and depressive symptom
burden were added. There was no statistically significant association between
serotonin noradrenaline reuptake inhibitor or tricyclic antidepressant use and OH
in unadjusted models although the study was not powered to detect changes within
these subgroups. Older people taking antidepressants have a two-fold higher
prevalence of OH than nonusers, highlighting the importance of screening the
older antidepressant user for OH and dizziness and rationalizing medications to
reduce the risk of falls within this vulnerable cohort.
PMID- 29937421
TI - Comparison of abdominal obesity measures in predicting of 10-year cardiovascular
risk in an Iranian adult population using ACC/AHA risk model: A population based
cross sectional study.
AB - BACKGROUND: Several abdominal obesity measures have been used for prediction of
10-year cardiovascular disease (CVD) risk but the superiority of these measures
remains controversial. The objective of this study was to assess the predictive
ability of abdominal obesity measures for risk of CVD events in an Iranian adult
population. METHODS: We analyzed the data of population based cross-section study
of 567 representative samples of adult population aged 40-70 years in Babol, the
north of Iran. The demographic data, the anthropometric measures, lipid profile
and cardiometabolic risk factors were measured with standard methods. Waist to
hip ratio (WHR), waist to height ratio (WHtR), conicity index(CI), abdominal
volume index (AVI) and body mass index(BMI)were calculated. The individual 10
year CVD risk was estimated based on ACC/AHA model. ROC analysis was performed to
assess the diagnostic ability of different abdominal obesity measures and body
mass index (BMI) in predicting of high risk of CVD events. RESULTS: About 42.5%
of men and 15% of women had at least 10% risk of 10-year cardiovascular events
and 21.1% of men and 3.0% of women had >=20% risk. Except WHR for men, all
abdominal obesity measures significant predictors for >=10% risk CVD risk in both
sexes but not BMI. The greater ability of CVD risk prediction was observed by
WHtR and CI in both sexes with higher AUC in females compared with men for >=10%
risk. CONCLUSION: WHtR and CI are superior indexes in predicting of high risk of
CVD events in both sexes.
PMID- 29937422
TI - Functional trajectories before and after a new cancer diagnosis among community
dwelling older adults.
AB - BACKGROUND: To characterize functional trajectories in the year before and after
a new cancer diagnosis among older adults and to identify risk factors for
worsening disability post-diagnosis. METHODS: We identified 170 participants 70+
years with monthly assessments of thirteen basic, instrumental, and mobility
activities and with a new cancer diagnosis from 1998 to 2014. A group-based
trajectory model identified distinct functional trajectories based on a total
disability score during the twelve months pre- and post-diagnosis. We evaluated
associations between potential risk factors at the time of cancer diagnosis and
worsening disability post-diagnosis, explored functional transitions from pre- to
post-diagnosis and identified participants whose functional trajectories
worsened. RESULTS: Three pre-diagnosis functional trajectories were identified
among 170 participants (mean age at diagnosis: 83 years (range: 73-105 years):
mild, moderate, and severe disability. Three post-diagnosis functional
trajectories were identified among 158 non-decedents: mild, moderate, and severe
disability. Most participants (93.9%) with severe disability pre-diagnosis had
severe disability post-diagnosis. Risk factors independently associated with
worsening disability post-diagnosis included moderate or severe disability pre
diagnosis (adjusted risk ratio, aRR: moderate: 2.96; 95%CI: 2.11-4.16; severe:
5.11; 95%CI: 3.07-8.52) vs. mild (reference), poor physical capability (aRR:
1.57; 95%CI: 1.07-2.30), and incurable stage (aRR:1.99; 95%CI: 1.41-2.80). 40% of
participants with a mild or moderate disability trajectory pre-diagnosis
transitioned to a worse functional trajectory post-diagnosis. CONCLUSION: Older
adults followed distinct functional trajectories in the twelve months before and
after cancer diagnosis. Functional trajectory pre-diagnosis, poor physical
capability, and incurable stage were independent risk factors for worsening
disability post-diagnosis.
PMID- 29937424
TI - The discovery of X-rays, the fate of atomic bomb survivors, and the impact on
modern interventional cardiology.
PMID- 29937423
TI - Protein-Protein Interaction Network Analysis of Salivary Proteomic Data in Oral
Cancer Cases
AB - Background: Oral cancer is a frequently encountered neoplasm of the head and neck
region, being the eight mostcommon type of human malignancy worldwide. Despite
improvement in its control, morbidity and mortality rates haveimproved little in
the past decades. Therefore, prevention and/or early detection are a high
priority. Proteomics withnetwork analysis have emerged as a powerful tool to
identify important proteins associated with cancer developmentand progression
that can be potential targets for early diagnosis. In the present study, network-
based protein- proteininteractions (PPI) for oral cancer were identified and then
analyzed for use as key proteins/potential biomarkers.Material and Methods: Gene
expression data in articles which focused on saliva proteomics of oral cancer
werecollected and 74 candidate genes or proteins were extracted. Related protein
networks of differentially expressed proteinswere explored and visualized using
cytoscape software. Further PPI analysis was performed by Molecular
ComplexDetection (MCODE) and BiNGO methods. Results: Network analysis of
genes/proteins related to oral cancer identifiedkininogen-1, angiotensinogen,
annexin A1, IL-8, IgG heavy variable and constant chains, CRP, collagen alpha-1
andfibronectin as 9 hub-bottleneck proteins. In addition, based on clustering
with the MCODE tool, vitronectin, collagenalpha-2, IL-8 and integrin alpha-v were
established as 5 distinct seed proteins. Conclusion: A hub-bottleneck
proteinpanel may offer a potential /candidate biomarker pattern for diagnosis and
treatment of oral cancer disease. Furtherinvestigation and validation of these
proteins are warranted.
PMID- 29937425
TI - Time for caution interpreting coronary physiology in aortic stenosis?
PMID- 29937426
TI - European registry data on LAA closure: advancing the field of interventional
stroke prevention.
PMID- 29937427
TI - No-reflow after percutaneous coronary intervention: a correlate of poor outcome
in both persistent and transient forms.
PMID- 29937428
TI - Percutaneous coronary intervention of saphenous vein grafts: where do we stand?
PMID- 29937429
TI - Transcatheter aortic valve implantation: don't forget the coronary arteries!
PMID- 29937432
TI - Prevalence, Predictors, and Prognostic Value of Residual Tricuspid Regurgitation
in Patients With Left Ventricular Assist Device.
AB - BACKGROUND: Although implantation of a left ventricular assist device (LVAD)
generally improves tricuspid regurgitation (TR) in short-term follow-up, the
clinical significance of residual TR in patients with mid- to long-term LVAD
support is unknown. This study aimed to identify the prevalence, predictors, and
prognostic value of residual TR in LVAD patients in association with tricuspid
valve (TV) deformation. METHODS AND RESULTS: The study cohort consisted of 127
patients who underwent LVAD implantation without TV procedure and were supported
with LVAD at least 1 year. All patients underwent echocardiographic examination
preoperatively and 1 year after LVAD implantation. TR was quantitatively assessed
by ratio of TR color jet area/right atrial area, and significant residual TR was
defined as >=20% of %TR at follow-up echocardiographic examination. Detailed
echocardiographic measurements were also performed, including TV annulus
diameter, TV leaflet displacement, and left ventricular and right ventricular
systolic function. LVAD implantation significantly improved ratio of TR color jet
area/right atrial area as well as left ventricular and right ventricular systolic
function and tethering distance (all P<0.05), whereas it enlarged TV annulus
diameter (P=0.002). Significant residual TR was observed in 30 (23.6%) patients.
Age, preoperative TV annulus diameter, and residual mitral regurgitation were
significantly associated with significant residual TR (all P<0.05), whereas TV
tethering was not. During a mean follow-up of 21+/-17 months, patients with
residual TR had significantly higher mortality than those without residual TR
(log-rank P<0.001). CONCLUSIONS: Significant residual TR was observed in ~25%
patients supported with LVAD over 1 year and was associated with unfavorable
outcome.
PMID- 29937431
TI - HbA1c and Hypoglycemia Reductions at 24 and 52 Weeks With Sotagliflozin in
Combination With Insulin in Adults With Type 1 Diabetes: The European inTandem2
Study.
AB - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of
the dual sodium-glucose cotransporter 1 and 2 inhibitor sotagliflozin compared
with placebo when combined with optimized insulin in adults with type 1 diabetes
(T1D). RESEARCH DESIGN AND METHODS: In a double-blind, 52-week, international
phase 3 trial, adults with T1D were randomized to placebo (n = 258) or once-daily
oral sotagliflozin 200 mg (n = 261) or 400 mg (n = 263) after 6 weeks of insulin
optimization. The primary outcome was change in HbA1c from baseline to 24 weeks.
The first secondary end point was a composite of the proportion of patients with
HbA1c <7.0%, no episode of severe hypoglycemia, and no episode of diabetic
ketoacidosis (DKA) at week 24. Fasting glucose, weight, insulin dose, and safety
end points were assessed through 52 weeks. RESULTS: At 24 weeks, placebo-adjusted
changes in HbA1c from baseline (7.8%) were -0.37% and -0.35% with sotagliflozin
200 and 400 mg, respectively (P < 0.001), and differences were maintained at 52
weeks. At 52 weeks, greater proportions of sotagliflozin-treated patients (200
mg: 25.67%; 400 mg: 26.62%) than placebo-treated patients (14.34%; P <= 0.001)
met the composite end point, and sotagliflozin 400 mg reduced fasting plasma
glucose (-0.87 mmol/L; P = 0.008), weight (-2.92 kg; P < 0.001), and total daily
insulin dose (-8.2%; P = 0.001). In a 24-week continuous glucose monitoring (CGM)
substudy, postprandial glucose decreased (P <= 0.009) and CGM demonstrated up to
3 h more time in the target range of 3.9-10.0 mmol/L with sotagliflozin.
Treatment satisfaction increased and diabetes distress decreased with
sotagliflozin (P < 0.05 vs. placebo). The frequency of documented hypoglycemia
was lower with sotagliflozin, and severe hypoglycemia occurred by week 52 in 13
patients (5.0%), 13 patients (5.0%), and 6 patients (2.3%) treated with placebo
and sotagliflozin 200 and 400 mg, respectively. DKA occurred in 0 of 258
patients, 6 of 261 patients (2.3%), and 9 of 263 patients (3.4%) in these
respective groups. CONCLUSIONS: In a 1-year study, sotagliflozin was associated
with statistically significant HbA1c reductions. More episodes of DKA and fewer
episodes of documented and severe hypoglycemia were observed in patients using
sotagliflozin relative to those receiving placebo (ClinicalTrials.gov,
NCT02421510).
PMID- 29937430
TI - Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1
Diabetes: The North American inTandem1 Study.
AB - OBJECTIVE: Evaluate the efficacy and safety of the dual sodium-glucose
cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with
optimized insulin in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The
inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American
adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or
sotagliflozin 400 mg (n = 262) after 6 weeks of insulin optimization. The primary
end point was HbA1c change from baseline at 24 weeks. HbA1c, weight, and safety
were also assessed through 52 weeks. RESULTS: From a mean baseline of 7.57%,
placebo-adjusted HbA1c reductions were 0.36% and 0.41% with sotagliflozin 200 and
400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all P <
0.001). Among patients with a baseline HbA1c >=7.0%, an HbA1c <7% was achieved by
15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and
sotagliflozin 400 mg, respectively (P <= 0.003 vs. placebo) at 24 weeks. At 52
weeks, mean treatment differences between sotagliflozin 400 mg and placebo were
1.08 mmol/L for fasting plasma glucose, -4.32 kg for weight, and -15.63% for
bolus insulin dose and -11.87% for basal insulin dose (all P < 0.001). Diabetes
Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points
with sotagliflozin versus placebo (P < 0.001) at 24 weeks. Genital mycotic
infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated
diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving
sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo.
Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group
and 26 (9.7%) patients receiving placebo. CONCLUSIONS: In a 1-year T1D study,
sotagliflozin combined with optimized insulin therapy was associated with
sustained HbA1c reduction, weight loss, lower insulin dose, fewer episodes of
severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to
placebo (ClinicalTrials.gov, NCT02384941).
PMID- 29937435
TI - Editorial.
PMID- 29937436
TI - Screening for founder and recurrent BRCA mutations in Hong Kong and US Chinese
populations.
PMID- 29937433
TI - Islet Long Noncoding RNAs: A Playbook for Discovery and Characterization.
AB - Diabetes is a complex group of metabolic disorders that can be accompanied by
several comorbidities, including increased risk of early death. Decades of
diabetes research have elucidated many genetic drivers of normal islet function
and dysfunction; however, a lack of suitable treatment options suggests our
knowledge about the disease remains incomplete. The establishment of long
noncoding RNAs (lncRNAs), once dismissed as "junk" DNA, as essential gene
regulators in many biological processes has redefined the central role for RNA in
cells. Studies showing that misregulation of lncRNAs can lead to disease have
contributed to the emergence of lncRNAs as attractive candidates for drug
targeting. These findings underscore the need to reexamine islet biology in the
context of a regulatory role for RNA. This review will 1) highlight what is known
about lncRNAs in the context of diabetes, 2) summarize the strategies used in
lncRNA discovery pipelines, and 3) discuss future directions and the potential
impact of studying the role of lncRNAs in diabetes.
PMID- 29937437
TI - Genetic screening for familial hypercholesterolaemia in Hong Kong.
PMID- 29937438
TI - Target-enriched massively parallel sequencing for genetic diagnosis of hereditary
hearing loss in patients with normal array CGH result.
PMID- 29937439
TI - Molecular diagnosis of severe combined immunodeficiency using whole-exome
sequencing.
PMID- 29937434
TI - Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors.
AB - Insulin-dependent diabetes may occur in patients with cancers who are treated
with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year
period at two academic institutions and identified 27 patients in whom this
developed, or an incidence of 0.9%. The patients had a variety of solid-organ
cancers, but all had received either anti-PD-1 or anti-PD-L1 antibodies. Diabetes
presented with ketoacidosis in 59%, and 42% had evidence of pancreatitis in the
peridiagnosis period. Forty percent had at least one positive autoantibody and
21% had two or more. There was a predominance of HLA-DR4, which was present in
76% of patients. Other immune adverse events were seen in 70%, and endocrine
adverse events in 44%. We conclude that autoimmune, insulin-dependent diabetes
occurs in close to 1% of patients treated with anti-PD-1 or -PD-L1 CPIs. This
syndrome has similarities and differences compared with classic type 1 diabetes.
The dominance of HLA-DR4 suggests an opportunity to identify those at highest
risk of these complications and to discover insights into the mechanisms of this
adverse event.
PMID- 29937440
TI - Apathy after stroke: potential risk factors and magnetic resonance imaging
markers.
PMID- 29937441
TI - Ictal intracranial electroencephalography using wavelet analysis of high
frequency oscillations in Chinese patients with refractory epilepsy.
PMID- 29937442
TI - Early neurodegenerative biomarkers and clinical outcome in psychiatric patients
with rapid eye movement sleep behaviour disorder: a prospective study.
PMID- 29937443
TI - Association of serum folate level with toxicity of capecitabine in patients with
colorectal cancers: a prospective cohort study.
PMID- 29937444
TI - Vitamin D deficiency among healthy infants in Hong Kong: a pilot study.
PMID- 29937445
TI - Reference range for brachial artery flow-mediated dilation in healthy Chinese
children and adolescents.
PMID- 29937446
TI - Association between childhood primary snoring and cardiovascular health.
PMID- 29937447
TI - Evaluation of a novel clinicopathological marker JK-1 for human oesophageal
carcinoma.
PMID- 29937448
TI - Soluble fms-like tyrosine kinase-1 and placental growth factor in Chinese
pregnant women during second and third trimesters.
PMID- 29937449
TI - Patient-specific seizure detection in long-term EEG using signal-derived
empirical mode decomposition (EMD)-based dictionary approach.
AB - OBJECTIVE: The objective of the work described in this paper is the development
of a computationally efficient methodology for patient-specific automatic seizure
detection in long-term multi-channel EEG recordings. APPROACH: A novel patient
specific seizure detection approach based on a signal-derived empirical mode
decomposition (EMD)-based dictionary approach is proposed. For this purpose, we
use an empirical framework for EMD-based dictionary creation and learning,
inspired by traditional dictionary learning methods, in which the EMD-based
dictionary is learned from the multi-channel EEG data being analyzed for
automatic seizure detection. We present the algorithm for dictionary creation and
learning, whose purpose is to learn dictionaries with a small number of atoms.
Using training signals belonging to seizure and non-seizure classes, an initial
dictionary, termed as the raw dictionary, is formed. The atoms of the raw
dictionary are composed of intrinsic mode functions obtained after decomposition
of the training signals using the empirical mode decomposition algorithm. The raw
dictionary is then trained using a learning algorithm, resulting in a substantial
decrease in the number of atoms in the trained dictionary. The trained dictionary
is then used for automatic seizure detection, such that coefficients of
orthogonal projections of test signals against the trained dictionary form the
features used for classification of test signals into seizure and non-seizure
classes. Thus no hand-engineered features have to be extracted from the data as
in traditional seizure detection approaches. MAIN RESULTS: The performance of the
proposed approach is validated using the CHB-MIT benchmark database, and averaged
accuracy, sensitivity and specificity values of 92.9%, 94.3% and 91.5%,
respectively, are obtained using support vector machine classifier and five-fold
cross-validation method. These results are compared with other approaches using
the same database, and the suitability of the approach for seizure detection in
long-term multi-channel EEG recordings is discussed. SIGNIFICANCE: The proposed
approach describes a computationally efficient method for automatic seizure
detection in long-term multi-channel EEG recordings. The method does not rely on
hand-engineered features, as are required in traditional approaches. Furthermore,
the approach is suitable for scenarios where the dictionary once formed and
trained can be used for automatic seizure detection of newly recorded data,
making the approach suitable for long-term multi-channel EEG recordings.
PMID- 29937450
TI - Efficacy and Safety of Trastuzumab in Combination with S-1 and Cisplatin Therapy
for Japanese Patients with HER2-Positive Advanced Gastric Cancer: Retrospective
Analysis.
AB - The combinations of oral fluoropyrimidines and cisplatin such as capecitabine and
cisplatin (XP) or S-1 and cisplatin (SP) are regarded as a standard therapy
against unresectable, recurrent, or advanced gastric cancer (AGC). Especially, SP
is the most common regimen against AGC in Japan. For patients with human
epidermal growth factor receptor type 2 (HER2)-positive AGC, trastuzumab, a
monoclonal antibody targeting HER2 antibody, is additionally used in combination.
Although trastuzumab in combination with XP (trastuzumab-XP) have been widely
accepted, the efficacy of trastuzumab in combination with SP (trastuzumab-SP)
lacks sufficient verification. The aim of the present study is to validate the
comparability of trastuzumab-SP to trastuzumab-XP. Patients with HER2-positive
AGC were assigned to the trastuzumab-XP or trastuzumab-SP group. We then
retrospectively compared the efficacy and safety between both groups. As a first
line chemotherapy, trastuzumab in combination with XP or SP was administered to
58 patients: 28 with trastuzumab-XP and 30 with trastuzumab-SP. In the
trastuzumab-XP group, response rate (RR), disease control rate (DCR), median
progression-free survival (mPFS), and median overall survival (mOS) were 39.3%,
89.3%, 7.9 months, and 20.0 months, respectively. In the trastuzumab-SP group,
RR, DCR, mPFS and mOS were 50.0%, 86.7%, 6.9 months, and 16.7 months,
respectively. No significant difference in efficacy was observed between both
groups. Severe hand-foot syndrome was observed more frequently in the trastuzumab
XP group than in the trastuzumab-SP group (14.3% vs. 0%, p = 0.05). Trastuzumab
in combination with SP is a potential first-line therapeutic option for patients
with HER2-positive AGC.
PMID- 29937453
TI - Functional comparison of anoctamin 1 antagonists on human uterine smooth muscle
contractility and excitability.
AB - BACKGROUND: Pre-term birth is a major health care challenge throughout the world,
and preterm labor represents a potentially reversible component of this problem.
Current tocolytics do not improve preterm labor beyond 48 h. We have previously
shown that anoctamin 1 (ANO1) channel blockade results in relaxation of pre
contracted human uterine smooth muscle (USM). Three drug classes with reported
medicinal effects in humans also have members with ANO1 antagonism. In this
study, we compared the ability of representatives from these 3 classes to reduce
human USM contractility and excitability. OBJECTIVE: This study sought to examine
the comparative potency of 3 ANO1 antagonists on pregnant human USM relaxation,
contraction frequency reduction, inhibition of intracellular calcium release and
membrane hyperpolarization. METHODS: Experiments were performed using: 1) Ex vivo
organ bath (human pregnant tissue), 2) Oxytocin-induced calcium flux (in vitro
human USM cells) and 3) Membrane potential assay (in vitro human USM cells).
RESULTS: Benzbromarone (BB) demonstrated the greatest potency among the compounds
tested with respect to force, frequency inhibition, reducing calcium elevation
and depolarizing membrane potential. CONCLUSION: While all 3 ANO1 antagonists
attenuate pregnant human uterine tissue contractility and excitability, BB is the
most potent tocolytic drug. Our findings may serve as a foundation for future
structure-function analyses for novel tocolytic drug development.
PMID- 29937454
TI - A Case of Cardiogenic Stroke After Thoracoscopic Left Atrial Appendectomy.
AB - Thoracoscopic left atrial appendectomy is a minimally invasive procedure for left
atrial appendage occlusion in patients with non-valvular atrial fibrillation,
particularly those at a great risk for both stroke and bleeding despite
appropriate oral anticoagulant therapy. It serves as an alternative strategy for
stroke risk reduction. Moreover, the oral anticoagulant therapy can be
discontinued after the operation. However, we encountered a 74-year old male
patient who developed cardiogenic stroke after thoracoscopic left atrial
appendectomy. We report this case to introduce how we evaluate the risk of
postoperative cardiogenic stroke by means of contrast-enhanced cardiac computed
tomography (CT), and how we formulate the postoperative patient management
strategy including short-term oral anticoagulation therapy by using results of
cardiac CT.
PMID- 29937455
TI - GVHD Prevention in 2018: Tried and True or Something New?
AB - Graft-versus-host disease (GVHD) is a major contributor to early and late
morbidity and mortality after allogeneic stem cell transplantation. Despite
results from a randomized controlled trial demonstrating an increased risk of
chronic GVHD with use of growth factor-mobilized peripheral blood stem cells
(PBSC) compared with bone marrow, PBSCs are the most widely used graft source in
allogeneic transplantation for hematologic neoplasms in the U.S. This lecture
will review established, recent, and novel strategies for GVHD prevention in
unrelated donor PBSC transplantation and will highlight ongoing clinical research
at Fred Hutchinson Cancer Research Center. Clinical trials aimed at defining
standard-of-care GVHD prophylaxis after myeloablative and nonmyelablative
conditioning will be presented. In addition, novel pharmacologic agents and graft
manipulation strategies under investigation will be discussed. (Presented at the
1962nd Meeting, May 12, 2018).
PMID- 29937456
TI - The regulatory effect of Genistein on granulosa cell in ovary of rat with PCOS
through Bcl-2 and Bax signaling pathways.
AB - The effect of genistein on Bcl-2 and Bax protein expression in the ovarian tissue
of rats with polycystic ovarian syndrome (PCOS) was evaluated. Sixty rats were
divided into six groups. Rats in the Dose group received genistein at a
concentration of either 5 (L-gen), 10 (M-Gen) or 20 (H-Gen) mg per kg of body
weight per day. The expression of Bcl-2 mRNA and Bax mRNA was determined by in
situ hybridization. Bcl-2 and Bax protein concentration was quantified by ELISA.
The results showed that the expression of Bcl-2 mRNA and Bcl-2 protein was
significantly higher in the high genistein Dose group (H-Gen) when compared to
the Model group (MG) (P<0.05). Genistein induced higher expression of the Bcl-2
gene at the transcriptional and translational level. Treatment with genistein
resulted in an improvement of ovarian function with Bcl-2 expression being
enhanced and Bax expression being suppressed. These alterations may be due to the
structural and functional modifications that take place in these cells, and could
be related to apoptotic changes that occur in rats with PCOS.
PMID- 29937457
TI - Effects of the angiotensin-converting enzyme inhibitor alacepril in dogs with
mitral valve disease.
AB - Alacepril is a relatively novel angiotensin-converting enzyme inhibitor; however,
the safety, tolerance, and efficacy of alacepril in terms of cough suppression in
dogs with mitral valve disease (MVD) remain unknown. The aim of this study was to
investigate the safety, tolerance, and cough suppression efficacy of alacepril in
dogs with MVD. This was a multi-center, prospective study. Forty-two dogs with
echocardiographic or radiographic evidence of cardiac enlargement in addition to
cough were enrolled. Dogs were treated with alacepril (1.0-3.0 mg/kg/day) for at
least 4 weeks. One dog (2.4%) developed complications, including appetite loss,
lethargy, and vomiting. Thirty-six dogs were re-evaluated after 4 weeks of
treatment. Cough resolved or improved in 20 dogs (55.6%) after treatment. Based
on the efficacy of alacepril, the dogs were divided into an effective group
(n=20) and an ineffective group (n=16). After treatment, the left ventricular end
diastolic internal diameter corrected for body weight was significantly increased
from baseline in the ineffective group but was significantly decreased in the
effective group. Univariate binomial logistic regression analyses showed that
high atrial natriuretic peptide level, N-terminal pro-B-type natriuretic peptide
level, and E wave velocity at baseline were significantly correlated with
alacepril inefficacy. Alacepril as treatment for MVD is well tolerated in most
dogs, and different conditions of cardiac loading may influence the effect of the
drug. Alacepril is expected to improve the quality of life of dogs with early
stage MVD.
PMID- 29937458
TI - The first clinical cases of Haemoproteus infection in a snowy owl (Bubo
scandiacus) and a goshawk (Accipiter gentilis) at a zoo in the Republic of Korea.
AB - This study reports two clinical cases of avian haemosporidian infection caused by
a Haemoproteus sp., involving a snowy owl (Bubo scandiacus) and a goshawk
(Accipiter gentilis), at a zoo. The snowy owl died after presenting with
anorexia, depression and lethargy. A blood smear with Wright's staining confirmed
Haemoproteus infection. Necropsy of the snowy owl revealed hypertrophy of the
internal organs, including the liver, gallbladder, kidney and adrenal glands. The
goshawk showed anorexia, depression and a lowered head position, and was
diagnosed with a Haemoproteus infection based on a blood smear. The goshawk was
completely cured by treatment with a combination of atovaquone and proguanil
hydrochloride. Both cases showed decreased erythrocytes, hemoglobin and
hematocrit values on complete blood count.
PMID- 29937459
TI - Therapeutic effects of oral clomiphene citrate in 2 dogs with low plasma
testosterone levels and poor semen quality.
AB - Two dogs with low plasma testosterone (T) levels and poor semen quality were
administered one tablet of 12.5 mg clomiphene citrate orally per day at 2-day
intervals for 4 weeks. Plasma T levels, total sperm count, and sperm motility in
both dogs temporarily increased between 3 and 6 weeks after the start of
treatment. These results indicate that poor semen quality in dogs with low plasma
T level can be improved by oral administration of clomiphene citrate.
PMID- 29937460
TI - Leader gene of Corynebacterium pseudotuberculosis may be useful in vaccines
against caseous lymphadenitis of goats: a bioinformatics approach.
AB - We conducted an in silico analysis to search for important genes in the
pathogenesis of Caseous Lymphadenitis (CL), with prospects for use in formulating
effective vaccines against this disease. For this, we performed a survey of
proteins expressed by Corynebacterium pseudotuberculosis, using protein sequences
collected from the NCBI GenPept database and the keywords "caseous lymphadenitis"
and "Corynebacterium pseudotuberculosis" and "goats". A network was developed
using the STRING 10 database, with a confidence score of 0.900. For every gene
interaction identified, we summed the interaction score of each gene, generating
a combined association score to obtain a single score named weighted number of
links (WNL). Genes with the highest WNL were named "leader genes". Ontological
analysis was extracted from the STRING database through Kyoto Encyclopedia of
Genes and Genomes (KEGG) database. A search in the GenPept database revealed
2,124 proteins. By using and plotting with STRING 10, we then developed an in
silico network model comprised of 1,243 genes/proteins interconnecting through
3,330 interactions. The highest WNL values were identified in the rplB gene,
which was named the leader gene. Our ontological analysis shows that this protein
acts effectively mainly on Metabolic pathways and Biosynthesis of secondary
metabolites. In conclusion, the in silico analyses showed that rplB has good
potential for vaccine development. However, functional assays are needed to make
sure that this protein can potentially induce both humoral and cellular immune
responses against C. pseudotuberculosis in goats.
PMID- 29937461
TI - Cow's milk neutralizes the cytotoxicity of acrolein, a putative carcinogen in
cigarette smoke.
AB - Cigarette smoke is a strong and independent risk factor for esophageal cancer,
while the consumption of cow's milk has been proposed as a protective factor. The
mechanistic role of milk in preventing cancer, however, has not been clarified.
We focused our study on acrolein, an abundant unsaturated aldehyde present in
cigarette smoke. Acrolein is a highly toxic compound and a putative carcinogen.
Using a cell culture system, we found that (1) acrolein caused necrosis in Ramos
Burkitt's lymphoma cells, (2) the necrosis was inhibited by preincubation of
acrolein with milk, and (3) acrolein formed adducts with milk proteins. These
results indicated the protective effects of cow's milk against acrolein-induced
cytotoxicity via protein-acrolein adduct formation.
PMID- 29937462
TI - Lymphoma-associated hemophagocytic syndrome in six dogs.
AB - Hemophagocytic syndrome (HPS) is a clinicopathological entity characterized by
histiocytic proliferation, with marked hemophagocytosis in the
reticuloendothelial organs. HPS caused by lymphoma is termed lymphoma-associated
hemophagocytic syndrome (LAHS), and there are few reports on canine and feline
LAHS. The objective of this study was to examine the clinical, diagnostic, and
clinicopathologic features of LAHS in six dogs. The diagnostic criteria of LAHS
consisted of lymphoma, bicytopenia or pancytopenia in the blood, and increased
hemophagocytosis in the reticuloendothelial organs. In one dog, an ocular form of
lymphoma was recognized. A splenic form was recognized in two dogs, and a
hepatosplenic form was recognized in three dogs. Immunophenotyping revealed T
cell origin in five dogs and B-cell origin in one dog by polymerase chain
reaction for antigen receptor rearrangement analysis. Nonspecific esterase stain
was performed to differentiate between neoplastic lymphocytes and hemophagocytes.
All five dogs with T-cell lymphoma were diagnosed with large granular lymphocyte
(LGL) lymphoma. In three cases, palliative therapy with glucocorticoids was
conducted, while the other three cases received chemotherapy as well. The
survival times for the three dogs with glucocorticoids only were 6, 6, and 10
days and were 30, 54, and 68 days for the three treated with anticancer therapy.
The median survival time for the dogs was 20 days. This report indicates that
canine LAHS is likely to be caused by LGL lymphoma, and it has an aggressive
behavior and poor general prognosis, as seen in humans.
PMID- 29937463
TI - Clinical, behavioral and biochemical alterations due to shearing stress in Ossimi
sheep.
AB - The effects of shearing on behavioral patterns, antioxidants, and inflammatory
and stress biomarkers was investigated in Ossimi sheep. Clinical parameters and
behavioral patterns were recorded, and serum samples were collected pre-shearing
and 1, 5, 10 and 15 days post-shearing from 60 Ossimi sheep. The results revealed
that grooming and standing idle frequencies were significantly (P<0.01) increased
post-shearing. There were significant (P<0.01) increases in IL-6, cortisol, and
MDA detected from the 1st to the 10th day post-shearing compared to pre-shearing
values. IL-2 and TNF-alpha significantly (P<0.01) increased from the 1st until
the 5th day post-shearing compared to pre-shearing values, while significant
(P<0.01) decreases in the values of catalase from the 1st until the 5th day post
shearing compared to pre-shearing values were recorded. Regarding to glutathione
reductase, there was a significant (P<0.01) decrease from the 1st until the 10th
day post-shearing compared to pre-shearing values. Shearing leads to significant
changes in antioxidants, inflammatory, stress biomarkers, and some behaviors in
sheep.
PMID- 29937464
TI - Usefulness of Buddy Wire Technique During Transcatheter Transseptal Mitral Valve
Implantation in Degenerated Mitral Bioprosthesis.
PMID- 29937467
TI - Association among genetic variants in the vitamin D pathway and circulating 25
hydroxyvitamin D levels in Korean adults: results from the Korea National Health
and Nutrition Examination Survey 2011-2012.
AB - Vitamin D deficiency affects >60% of the Korean population. Recent reports in
Caucasian, African American, and Chinese populations indicate an association
between vitamin D status and related single nucleotide polymorphisms (SNPs), but
specific associations differ among study populations. We investigated the
relationship between five SNPs involved in the vitamin D metabolic pathway (DHCR7
rs12785878, GC rs2282679, CYP2R1 rs12794714, CYP2R1 rs10741657, and CYP24A1
rs6013897) and serum 25-hydroxyvitamin D [25(OH)D] status in Koreans using the
Korea National Health and Nutrition Examination Survey, a nationwide database.
Whether the association was modified by demographic and lifestyle factors,
including sex, body mass index (BMI), smoking status, drinking status, physical
activity, and sun exposure, were also investigated. The results showed the serum
level of 25(OH)D was associated with rs12785878, rs2282679, and rs12794714
genotypes, but not with rs10741657 or rs6013897. The genetic risk score (GRS)
calculated by summing the number of alleles of these 5 SNPs was associated with
low circulating levels of 25(OH)D. However, the negative association between
25(OH)D and GRS was modified by obesity and sun exposure. Specifically, negative
associations between 25(OH)D and GRS were present in adults with lower BMI (<25
kg/m2) and longer sun exposure time (>=2 h/day). In conclusion, common variants
of vitamin D-related SNPs are associated with vitamin D status in Koreans, and
this genetic effect was masked when BMI >=25 kg/m2 or sun exposure <2 h/day.
Additionally, seasonal variation must be considered in future studies among
Koreans.
PMID- 29937466
TI - Enduring remission of active and sight-threatening Graves' orbitopathy with
rituximab: report of two cases.
AB - Intravenous (i.v.) glucocorticosteroids (GCs) constitute the first-line treatment
for active and moderate-to-severe Graves' orbitopathy (GO). In cases of
persistent disease, rituximab, a monoclonal anti-CD20 antibody, may be used,
although studies have yielded conflicting results. In case 1, a 50-year-old
female heavy smoker presented with severe bilateral disfiguring eyelid edema of
four months, bilateral exophthalmos and a clinical activity score (CAS) of 5/7.
Laboratory investigation showed thyrotoxicosis and high thyroid-stimulating
immunoglobulin (TSI) levels [32 IU/L (normal <1.75]. After minor improvement by
i.v. methylprednisolone and standard retrobulbar radiotherapy (20 Gy), her visual
acuity progressively declined to "hand motion". Rituximab was administered (two
pulses of 500 mg, two weeks apart), with significant response. At 3 1/2 years of
follow-up, CAS is 0/7 and CD20+ lymphocytes remain at the lower normal range. In
case 2, a 78-year-old non-smoker male was referred for management of severe
active GO, one month after total thyroidectomy for Graves' thyrotoxicosis (TSI:
6.74 IU/L). Over the preceding two-three months, severe GO manifested with
chemosis, constant diplopia, loss of color vision and acuity of 1/10 bilaterally
(CAS: 7/7). Following partial response to i.v. methylprednisolone and concomitant
radiotherapy, rituximab (two pulses of 500 mg each, two weeks apart), was
administered. Vision partially recovered and GO remains in remission one year
later, even after 131I (100 mCi) administration for papillary thyroid carcinoma
(TSI: 0.9 IU/L and CD20+ count at the lower normal range). In conclusion,
rituximab may be an effective second-line therapy in GO patients, providing long
lasting remission.
PMID- 29937465
TI - Heat stress impairs gap junction communication and cumulus function of bovine
oocytes.
AB - The intimate association of cumulus cells with one another and with the oocyte is
important for regulating oocyte meiotic arrest and resumption. The objective of
this study was to determine the effects of heat stress on cumulus cell
communication and functions that may be related to accelerated oocyte meiosis
during early maturation. Bovine cumulus-oocyte complexes underwent in vitro
maturation for up to 6 h at thermoneutral control (38.5 degrees C) or elevated
(40.0, 41.0 or 42.0 degrees C) temperatures. Gap junction communication between
the cumulus cells and the oocyte was assessed using the fluorescent dye calcein
after 4 h of in vitro maturation. Dye transfer was reduced in cumulus-oocyte
complexes matured at 41.0 degrees C or 42.0 degrees C; transfer at 40.0 degrees C
was similar to control (P < 0.0001). Subsequent staining of oocytes with Hoechst
revealed that oocytes matured at 41.0 or 42.0 degrees C contained chromatin at
more advanced stages of condensation. Maturation of cumulus-oocyte complexes at
elevated temperatures reduced levels of active 5' adenosine monophosphate
activated kinase (P = 0.03). Heat stress exposure had no effect on active
extracellular-regulated kinase 1/2 in oocytes (P = 0.67), associated cumulus
cells (P = 0.60) or intact cumulus-oocyte complexes (P = 0.44). Heat-induced
increases in progesterone production by cumulus-oocyte complexes were detected
during the first 6 h of maturation (P = 0.001). Heat-induced alterations in gap
junction communication and other cumulus-cell functions likely cooperate to
accelerate bovine oocyte meiotic progression.
PMID- 29937468
TI - Efficacy of Pericardial Drainage in Annular Rupture and Periaortic Hematoma After
Transcatheter Aortic Valve Replacement.
PMID- 29937469
TI - Contribution of Diabetes to the Incidence and Prevalence of Comorbid Conditions
(Cancer, Periodontal Disease, Fracture, Impaired Cognitive Function, and
Depression): A Systematic Review of Epidemiological Studies in Japanese
Populations.
AB - BACKGROUND: Several epidemiological studies have determined the relationship
between diabetes and the incidence and/or prevalence of recently identified
comorbid conditions (cancer, periodontal disease, fracture, cognitive impairment,
and depression). These relationships may vary by country or race/ethnicity. We
aimed to systematically review studies in this field conducted with the Japanese
population because such a review in the Japanese population has never been
undertaken. METHODS: We conducted systematic literature searches in PubMed and
Ichushi-Web databases for studies published until December 2016. Studies
comparing the incidence and/or prevalence of the comorbidities among the Japanese
population were included. The studies were classified as integrated analyses,
cohort studies, case-control studies, or cross-sectional studies. RESULTS: We
identified 33 studies (cancer: 17, periodontal disease: 5, fracture: 5, cognitive
impairment: 4, and depression: 2). Although several cohort studies and meta
analyses had assessed the development of cancer in diabetes, there was scant
epidemiological evidence for the other conditions. Indeed, only one cohort study
each had been conducted for periodontal disease, fracture, and cognitive
impairment, whereas other evidence was cross-sectional, some of which was induced
from baseline characteristic tables of studies designed for other purposes.
CONCLUSION: In Japan, there is insufficient evidence about the relationship
between diabetes and the incidence/prevalence of periodontal disease, fracture,
cognitive impairment, and depression. By contrast, several cohort studies and
integrated analyses have been conducted for the relationship with cancer. Further
studies should be undertaken to estimate the contribution of diabetes on the
incidence/prevalence of comorbidities that may be specific to the Japanese
population.
PMID- 29937470
TI - Exploring 2.5-Year Trajectories of Functional Decline in Older Adults by Applying
a Growth Mixture Model and Frequency of Outings as a Predictor: A 2010-2013 JAGES
Longitudinal Study.
AB - BACKGROUND: We explored the distinct trajectories of functional decline among
older adults in Japan, and evaluated whether the frequency of outings, an
important indicator of social activity, predicts the identified trajectories.
METHODS: We analyzed data on 2,364 adults aged 65 years or older from the Japan
Aichi Gerontological Evaluation Study. Participants were initially independent
and later developed functional disability during a 31-month follow-up period. We
used the level of long-term care needs certified in the public health insurance
system as a proxy of functional ability and linked the fully tracked data of
changes in the care levels to the baseline data. A low frequency of outings was
defined as leaving one's home less than once per week at baseline. We applied a
growth mixture model to identify trajectories in functional decline by sex and
then examined the association between the frequency of outings and the identified
trajectories using multinomial logistic regression analysis. RESULTS: Three
distinct trajectories were identified: "slowly declining" (64.3% of men and 79.7%
of women), "persistently disabled" (4.5% and 3.7%, respectively), and "rapidly
declining" (31.3% and 16.6%, respectively). Men with fewer outings had 2.14 times
greater odds (95% confidence interval, 1.03-4.41) of being persistently disabled.
The association between outing frequency and functional decline trajectory was
less clear statistically among women. CONCLUSIONS: While the majority of older
adults showed a slow functional decline, some showed persistent moderate
disability. Providing more opportunities to go out or assistance in that regard
may be important for preventing persistent disability, and such needs might be
greater among men.
PMID- 29937471
TI - Cedar Pollinosis and Mortality: A Population-Based Prospective Cohort Study in
Japan.
AB - BACKGROUND: Cedar pollinosis is one of the most prevalent forms of seasonal
allergic reaction in Japan. Only one prospective study has examined the
association between cedar pollinosis and mortality. Using a symptom-based
questionnaire on cedar pollinosis, we investigated the association of cedar
pollinosis with all-cause and cause-specific mortality. METHODS: Data came from
the Takayama Study, which recruited residents aged >=35 years in 1992 from
Takayama city in Gifu Prefecture, Japan. The current study used information on
cedar pollinosis that was obtained from the second survey in 2002. A total of
12,471 persons who were 45-80 years old and had no history of cancer, coronary
heart disease, or stroke responded to a questionnaire asking about four symptoms
related to cedar pollinosis. Mortality and migration data were obtained
throughout the follow-up period up to March 2013. Cox proportional hazard models
were used to examine the relation between cedar pollinosis and mortality.
RESULTS: A total of 1,276 persons died during follow-up period. Among these,
there were 504 neoplasm, 278 cardiovascular, and 181 respiratory deaths. After
adjusting for potential confounders, cedar pollinosis was associated with
significantly lower all-cause mortality (hazard ratio [HR] 0.79; 95% confidence
interval [CI], 0.65-0.95) and respiratory mortality (HR 0.38; 95% CI, 0.18-0.82).
There was no significant association between cedar pollinosis and mortality due
to neoplasm or cardiovascular disease. CONCLUSIONS: We found an inverse
association between cedar pollinosis and the risk of all-cause and respiratory
mortality. Further research is needed to elucidate the association between cedar
pollinosis and mortality.
PMID- 29937472
TI - PINK1 Expression Is Associated with Poor Prognosis in Lung Adenocarcinoma.
AB - PTEN-induced putative kinase protein 1 (PINK1) is a serine/threonine-protein
kinase that phosphorylates mitochondrial proteins and is involved in mitophagy.
Thus, PINK1 may protect cancer cells against mitochondrial dysfunction during
cellular stress. However, the role of PINK1 in lung cancer was rarely explored.
In this study, we immunohistochemically analyzed the expression of PINK1 in 256
patients with non-small-cell lung cancer, consisting of 137 patients with
adenocarcinoma (AC) and 119 patients with squamous cell carcinoma (SCC). In
particular, we focused on the difference in diagnostic or prognostic value of
PINK1 expression between AC patients and SCC patients. The patients with AC or
SCC were divided into high or low PINK1 expression group, according to the
immunohistochemical score that was based on the percentage of PINK1 positive
cells and staining intensity. Among the 137 AC specimens, 52 specimens (37.96%)
were judged as high PINK1 expression, and likewise, among 119 SCC specimens, 42
specimens (35.29%) were judged as high PINK1 expression. Importantly, high PINK1
expression was significantly associated with postoperative chemoresistance of AC,
but not in case of SCC. Moreover, high PINK1 expression was identified as a poor
prognostic factor for AC, but not for SCC. These results may reflect the
biological difference between AC and SCC. In conclusion, high PINK1 expression is
correlated with poor response to chemotherapy and is an independent prognostic
factor for AC, but not for SCC. Our findings suggest that PINK1 detection could
help stratify patients who may have poor response to chemotherapy and guide the
individual treatment.
PMID- 29937473
TI - Protective effect of a mechanistic target of rapamycin inhibitor on an in vivo
model ofcisplatin-induced ovarian gonadotoxicity.
AB - This study aimed to evaluate the protective effect of everolimus, a mechanistic
target of rapamycin (mTOR) inhibitor, on cisplatin chemotherapy-induced ovarian
toxicity. Eighty sexually mature, virgin, female, 7-week-old C57BL/6J mice were
divided into four groups: control, cisplatin (Cis), everolimus (mTORi), and
everolimus plus cisplatin (mTORi+Cis). Mice in the Cis and mTORi+Cis groups were
intraperitoneally injected with 2 mg/kg of cisplatin for 15 d. Mice in the mTORi
and mTORi+Cis groups were orally administered 2.5 mg/kg of everolimus for 29 d,
from one week before the first cisplatin injection to one week after the last
cisplatin injection. Histological examinations were performed 24 h after the last
everolimus administration. The primordial, primary, and antral follicles were
significantly depleted in the Cis group compared with that in the control group,
confirming the gonadotoxicity of cisplatin. The number of primordial, secondary,
and antral follicles was significantly higher in the mTORi+Cis group than in the
Cis group, thereby displaying the effect of mTORi-treatment on ovarian
protection. Primordial, secondary, and antral follicle counts were similar in the
mTORi+Cis and the control groups. The results of this study indicate a protective
effect of an mTOR inhibitor against cisplatin chemotherapy-induced gonadotoxicity
in the ovarian reserve in an in vivo mouse model.
PMID- 29937474
TI - Improvement of inspection system for reduction of small-scale construction site
accident in Korea.
AB - This study analyzed the trend of construction accidents focused on the small
scale construction sites and the correlation between the ratios of official
inspection by government and total fatality injuries per 10,000 people (TFR) by
construction size in Korea. The method is to analyze statistical data for the
construction accidents and official safety inspection system. In construction,
accidents rate and TFR are recently increasing unlike other industries. In
addition, the smaller the scale of construction sites, the higher the TFR, and
vice versa. The smaller the scale of construction sites, the greater the degree
of difference in the TFR for each year, and vice versa. In small-scale
construction sites, which have amounted less than $273,000 (L231,000),
approximately 45.7% of deaths occurred on sites between $36,400 (L30,800) and
$182,000 (L154,000). The ratio of inspection, which represents the ratio of
official inspection proportion to site share, is in inverse proportion to the TFR
by construction size. As the ratio approached zero, TFR became higher, and the
higher the ratio, the lower TFR since the official inspection was mainly carried
out in medium and large-scale construction sites. To get an effect of official
inspection, the focus of official inspection should move onto the small-scale
construction site.
PMID- 29937475
TI - Charge elimination method for a charged roll using a passive type ionizer with an
air assist.
AB - The charge elimination method for moving charged objects was investigated using a
passive type ionizer with an air assist to effectively eliminate the static
charge generated at high speed by the roll-to-roll process. The passive ionizer
has a grounded needle placed horizontally with respect to the moving charged roll
and an air hole to eject an air flow to transport the ions from the grounded
needle. The passive ionizer releases ions from the grounded needle electrode when
the electric field at the tip of the grounded needle exceeds the corona inception
condition. The experimental set up is composed of a moving charged roll, the
passive ionizer and surface voltmeters for evaluating performance. The charge
elimination current Ie, which corresponds to the amount of ions produced per
second was measured for various movement speeds and charge potentials of the
charged roll. Supply of the air flow beneath the needle electrode increased Ie
because the ions were effectively transported to a place where the charge
elimination of the roll did not affect the corona onset condition. The difference
in charge elimination performance between the proposed ionizer and a commercial
active ionizer was clarified in terms of Ie and the charge elimination rate.
PMID- 29937476
TI - Unstable behavior of segmental ring under various pressures and its discrete
element simulation.
AB - In February 2012, a serious accident which resulted in five fatalities happened
during a TBM-tunnel construction under the seabed in Japan. The cause of the
accident appeared to be due to the Key-segment slipping out of the segment ring
by the thrusting tailskin (wire brushes) of the TBM into the segment ring. This
resulted in the collapse of the rings, causing the seabed ground and seawater to
flow into the tunnel. We investigated how thin and thick segments without any
circumferential joints behave under isotropic and anisotropic pressures using
small-scale physical model. In the model tests, pressures were applied to the
surroundings of the segment rings and the strains at each segment were measured
in order to evaluate the damage. In addition, cases where lubrication on the
contact area between the K- and B-segments was present or not were investigated
and their discrete element simulations were also conducted.
PMID- 29937477
TI - Erratum: J Reprod Dev, Vol. 64, No. 2, p. 153-160, Macromolecular crowded
conditions strengthen contacts between mouse oocytes and companion granulosa
cells during in vitro growth.
AB - Figure 7 have been corrected.
PMID- 29937478
TI - Frequency of complications of falling from the walnut tree, as an occupational
seasonal injury.
AB - BACKGROUND: Falling from a tree is one of the major causes of serious injuries in
farmers but it can be prevented. Walnut is one of the most important agricultural
products in Iran and falling from walnut trees is common during the season of
harvest. The aim of this study was to determine the frequency of complications
due to falling from walnut tree in patients referred to the emergency department
of Imam Ali Hospital in Bojnurd City, Iran. METHODS: A descriptive cross
sectional study was conducted on 127 patients with injuries due to falling from
the walnut tree in Bojnurd City, Iran, in the walnut harvest season of August
2013 to November 2014. The tools used for data collection in this study included
a demographic information form, checklists of information about the injury and
the follow-up checklist of treatment. Data were analyzed using descriptive
statistics by the SPSS software version 16. RESULTS: From a total of 127 injured
patients, 120 cases (94.4%) were males with a mean age of 36.49 +/- 15.65 years.
Five patients died on the day of admission. Eighty two patients (64.56%) were
admitted in hospital wards. The most common type of injuries were trunk injuries
(26.19%), followed by spinal cord injuries (18.1%). Also, 7 patients suffered
from complete spinal cord injury. CONCLUSIONS: Injuries caused by falling from
walnut trees are seasonal and impose large financial burden on our health system.
In most cases, young men suffer from varying degrees of disability and experience
financial problems. It is very important to train farmers and workers, so as to
prevent such injuries.
PMID- 29937479
TI - Telomerase Reverse Transcriptase Contains a BH3-Like Motif and Interacts with BCL
2 Family Members.
AB - Upregulation of human telomerase reverse transcriptase (hTERT) expression is an
important factor in the cellular survival and cancer. Although growing evidence
suggests that hTERT inhibits cellular apoptosis by telomere-independent
functions, the mechanisms involved are not fully understood. Here, we show that
hTERT contains a BH3-like motif, a short peptide sequence found in BCL-2 family
proteins, and interacts with anti-apoptotic BCL-2 family proteins MCL-1 and BCL
xL, suggesting a functional link between hTERT and the mitochondrial pathway of
apoptosis. Additionally, we propose that hTERT can be categorized into the
atypical BH3-only proteins that promote cellular survival, possibly due to the
non-canonical interaction between hTERT and antiapoptotic proteins. Although the
detailed mechanisms underlying the hTERT BH3-like motif functions and
interactions between hTERT and BCL-2 family proteins have not been elucidated,
this work proposes a possible connection between hTERT and BCL-2 family members
and reconsiders the role of the BH3-like motif as an interaction motif.
PMID- 29937480
TI - Estimated Burden of Serious Fungal Infections in Mozambique.
AB - Mozambique is a sub-Saharan African country with limited information on the
burden of fungal disease. We estimate the burden of serious fungal infections for
the general healthy population and for those at risk, including those infected
with HIV, patients with asthma, as well as those under intensive care. We consult
the Mozambican National Institute of Statistics Population and Housing Census
report to obtain denominators for different age groups. We use modelling and HIV
data to estimate the burdens of Pneumocystis jirovecii pneumonia (PCP),
Cryptococcal meningitis (CM) and candidiasis. Asthma, chronic obstructive
pulmonary disease and tuberculosis data were used to estimate the burden of
allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary
aspergillosis (CPA). In 2016, the Mozambique population was 26.4 million with 1.8
million people reported to be HIV-infected. Estimated annual incidence of fungal
infections was: 33,380 PCP, 18,640 CM and 260,025 oral and oesophageal
candidiasis cases. Following pulmonary tuberculosis, estimated numbers of people
having chronic pulmonary aspergillosis (prevalence) and allergic bronchopulmonary
aspergillosis complicating asthma are 18,475 and 15,626, respectively. Tinea
capitis is common in children with over 1.1 million probably affected. We also
highlight from studies in progress of high incidences of Histoplasmosis, CM and
Pneumocystis jirovecii in adult HIV-infected patients. Prospective epidemiology
studies with sensitive diagnostics are required to validate these estimates.
PMID- 29937481
TI - Phoma Infections: Classification, Potential Food Sources, and Its Clinical
Impact.
AB - Phoma species are phytopathogens that are widely distributed in the environment,
most commonly found in aquatic systems and soil. Phoma spp. have the potential to
be pathogenic in plants, animals and humans; the latter is a rare occurrence.
However, as our immunocompromised population increases, so do the reports of
these infections. Medical advances have allowed for the increase in solid organ
transplantation; chemotherapies to treat malignancies; and the use of other
immunosuppressive agents, which have resulted in a greater population at risk
when exposed to diverse fungi including Phoma spp. These fungi have been isolated
from water sources, food, and crops; thus acting as opportunistic pathogens when
the right host is exposed. Phoma spp. contaminates common food sources such as
potatoes and maize, a common species isolated being Phoma sorghina. Though there
is potential for causing infection via consumption of contaminated foods, there
is insufficient data detailing what levels of organism can lead to an infection,
and a regulated process for detecting the organism. The spectrum of disease is
wide, depending on the host, ranging from cutaneous infections to invasive
diseases. Mortality, however, remains low.
PMID- 29937482
TI - Microbial Hydrolysis of Racemic beta-Aryl-gamma-ethylidene-gamma-lactones and
Antifeedant Activity of the Products against Alphitobius diaperinus Panzer.
AB - Hydrolysis of (+/-)-β-aryl-γ-ethylidene-γ-lactones by fungal
strain Aspergillus ochraceus AM370 afforded (−)-(S)-γ-ethylidene
γ-lactones 2a-d and (+)-(R)-γ-ketoacids 3a-d. Enantiomeric purity of
the unreacted lactones was strictly related to a size of an aryl substituent at C
4 of γ-lactone ring, with the highest ee (77%) obtained for the (−)
(S)-γ-ethylidene-γ-lactone possessing unsubstituted benzene ring (2a)
and the lowest one (15%) determined for the (−)-(S)-γ-ethylidene
γ-lactone with bulky 1,3-benzodioxole system (2d). Lactones 2a-d, both
racemic and enantiomerically enriched, as well as products of their hydrolysis
showed varying degrees of feeding deterrent activity against lesser mealworm,
Alphitobius diaperinus Panzer, which depended on the structure of the compound
and the developmental stage of the lesser mealworm. In the case of adults, more
active were γ-lactones 2a-d, compared with ketoacids 3a-d. Only in the case
of lactone 2a was the effect of configuration of stereogenic center on the
activity found. Particularly strong deterrents against this stage (T > 180) were
racemic and (−)-(S)-γ-ethylidene-γ-lactone with p
methoxysubstituted phenyl ring (2c).
PMID- 29937484
TI - N-3 Polyunsatured Fatty Acids in Menopausal Transition: A Systematic Review of
Depressive and Cognitive Disorders with Accompanying Vasomotor Symptoms.
AB - Depression is one of the most important health problems worldwide. Women are 2.5
times more likely to experience major depression than men. Evidence suggests that
some women might experience an increased risk for developing depression during
“windows of vulnerability”, i.e., when exposed to intense hormone
fluctuations, such as the menopause transition. Indeed, this period is associated
with different symptoms, including vasomotor, depressive, and cognitive symptoms,
which have all been shown to worsen as women approach menopause. Even though
hormonal therapy represents the most effective treatment, side effects have been
reported by several studies. Therefore, an increased number of women might prefer
the use of alternative medicine for treating menopausal symptoms. N-3 long-chain
polyunsaturated fatty acids (n-3 LCPUFAs) are included among these alternative
treatments. We here provide a review of studies investigating the effects of n-3
LCPUFAs on hot flashes and depressive and cognitive disorders in menopausal
women. The reported results are scattered and heterogeneous. In conclusion, a
beneficial role of n-3 LCPUFAs in hot flashes, and depressive and cognitive
symptoms related to menopausal transition is still far from conclusive.
PMID- 29937483
TI - Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability
Enhancement of Poorly Water-Soluble Drugs.
AB - Over the past decades, a large number of drugs as well as drug candidates with
poor dissolution characteristics have been witnessed, which invokes great
interest in enabling formulation of these active ingredients. Poorly water
soluble drugs, especially biopharmaceutical classification system (BCS) II ones,
are preferably designed as oral dosage forms if the dissolution limit can be
broken through. Minimizing a drug’s size is an effective means to increase
its dissolution and hence the bioavailability, which can be achieved by
specialized dispersion techniques. This article reviews the most commonly used
dispersion techniques for pharmaceutical processing that can practically enhance
the dissolution and bioavailability of poorly water-soluble drugs. Major
interests focus on solid dispersion, lipid-based dispersion (nanoencapsulation),
and liquisolid dispersion (drug solubilized in a non-volatile solvent and
dispersed in suitable solid excipients for tableting or capsulizing), covering
the formulation development, preparative technique and potential applications for
oral drug delivery. Otherwise, some other techniques that can increase the
dispersibility of a drug such as co-precipitation, concomitant crystallization
and inclusion complexation are also discussed. Various dispersion techniques
provide a productive platform for addressing the formulation challenge of poorly
water-soluble drugs. Solid dispersion and liquisolid dispersion are most likely
to be successful in developing oral dosage forms. Lipid-based dispersion
represents a promising approach to surmounting the bioavailability of low
permeable drugs, though the technique needs to traverse the obstacle from liquid
to solid transformation. Novel dispersion techniques are highly encouraged to
develop for formulation of poorly water-soluble drugs.
PMID- 29937485
TI - Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities.
AB - Recent studies suggest that the commensal microbiota affects not only host energy
metabolism and development of immunity but also bone remodeling by positive
regulation of osteoclast activity. However, the mechanism of regulation of bone
cells by the commensal microbiota has not been elucidated. In this study, 8-week
old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms
of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT
analysis showed that SPF mice had larger body size associated with lower bone
mineral density and bone volume fraction in alveolar bones compared with GF mice.
Greater numbers of osteoclasts in alveolar bone and higher serum levels of
tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts
from SPF alveolar bone showed higher levels of cathepsin K, indicating higher
osteoclast activity. SPF alveolar extracts also showed elevated levels of γ
carboxylated glutamic acid-osteocalcin as a marker of mature osteoblasts compared
with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly
isolated from alveolar bone showed that in SPF mice, expression of mRNA of
osteocalcin, which also acts as an inhibitor of bone mineralization, was strongly
enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice
showed reduced mineralization but significantly enhanced expression of mRNAs of
osteocalcin, alkaline phosphatase, insulin-like growth factor-I/II, and decreased
ratio of osteoprotegerin/receptor activator of nuclear factor-kappa B ligand
compared with GF mice. Furthermore, PCR array analyses of transcription factors
in cultured calvarial osteoblasts showed strongly upregulated expression of
Forkhead box g1. In contrast, Gata-binding protein 3 was strongly downregulated
in SPF osteoblasts. These results suggest that the commensal microbiota prevents
excessive mineralization possibly by stimulating osteocalcin expression in
osteoblasts, and enhances both osteoblast and osteoclast activity by regulating
specific transcription factors.
PMID- 29937488
TI - Effects of Blank Quality on Press-Formed PEKK/Carbon Composite Parts.
AB - The causes of delamination and porosities during press forming of pre
consolidated flat laminates (blanks) made of carbon fiber-reinforced poly(ether
ketone ketone) (PEKK) were addressed in this study. In particular, the quality of
the blank laminate was investigated before and after infrared heating. The
consolidation quality was evaluated by thickness measurements, non-destructive
inspection (NDI), and optical microscopy. The experimental results confirmed that
deconsolidation phenomena can be related to residual stresses formed during blank
forming in an autoclave, then released during infrared heating (IR) of the blank,
determining most of the defects in IR heated blanks. These defects, generated at
the pre-heating stage, were not fully removed in the consolidation stage of the
press forming process. An annealing treatment, performed on autoclave
consolidated blanks above the glass transition temperature of the matrix, was
proposed to reduce the formation of defects during IR heating. The stress
relaxation phenomena during annealing were modelled using a simple viscoelastic
model.
PMID- 29937489
TI - Effects of Organic Modification of Montmorillonite on the Properties of
Hydroxypropyl Di-Starch Phosphate Films Prepared by Extrusion Blowing.
AB - The knowledge gained from starch-nanocomposite-film research has not been fully
applied commercially because of the lack of appropriate industrial processing
techniques for nanofillers and starch films. Three organically modified
montmorillonites (OMMTs) were prepared using a semidry kneading method. The
effects of the OMMTs on the structures and properties of starch nanocomposite
films, prepared by extrusion blowing, were investigated. The X-ray diffraction
(XRD) analysis results revealed that the OMMTs with various quaternary ammonium
salts possessed differing layer structures and d-space values. The results of the
XRD and Fourier-transform infrared spectroscopy (FT-IR) showed that the starch
OMMT interaction resulted in a structural change, namely the starch-OMMT films
possessed a balanced exfoliated and intercalated nanostructure, while the starch
MMT film possessed an exfoliated nanostructure with non-intercalated
montmorillonite (MMT). The results of the solid-state nuclear magnetic resonance
(NMR) analysis suggested that the starch-OMMT nanocomposite possessed
comparatively large quantities of single-helix structures and micro-ordered
amorphous regions. The starch-OMMT films exhibited good tensile strength (TS)
(maximum of 6.09 MPa) and water barrier properties (minimum of 3.48 ×
10−10 g·m·m−2·s−1·Pa−1). This
study indicates that the addition of OMMTs is a promising strategy to improve the
properties of starch films.
PMID- 29937487
TI - Evolutionary History of the Glycoside Hydrolase 3 (GH3) Family Based on the
Sequenced Genomes of 48 Plants and Identification of Jasmonic Acid-Related GH3
Proteins in Solanum tuberosum.
AB - Glycoside Hydrolase 3 (GH3) is a phytohormone-responsive family of proteins found
in many plant species. These proteins contribute to the biological activity of
indolacetic acid (IAA), jasmonic acid (JA), and salicylic acid (SA). They also
affect plant growth and developmental processes as well as some types of stress.
In this study, GH3 genes were identified in 48 plant species, including algae,
mosses, ferns, gymnosperms, and angiosperms. No GH3 representative protein was
found in algae, but we identified 4 genes in mosses, 19 in ferns, 7 in
gymnosperms, and several in angiosperms. The results showed that GH3 proteins are
mainly present in seed plants. Phylogenetic analysis of all GH3 proteins showed
three separate clades. Group I was related to JA adenylation, group II was
related to IAA adenylation, and group III was separated from group II, but its
function was not clear. The structure of the GH3 proteins indicated highly
conserved sequences in the plant kingdom. The analysis of JA adenylation in
relation to gene expression of GH3 in potato (Solanum tuberosum) showed that
StGH3.12 greatly responded to methyl jasmonate (MeJA) treatment. The expression
levels of StGH3.1, StGH3.11, and StGH3.12 were higher in the potato flowers, and
StGH3.11 expression was also higher in the stolon. Our research revealed the
evolution of the GH3 family, which is useful for studying the precise function of
GH3 proteins related to JA adenylation in S. tuberosum when the plants are
developing and under biotic stress.
PMID- 29937486
TI - Nutrients, Nutraceuticals, and Xenobiotics Affecting Renal Health.
AB - Chronic kidney disease (CKD) affects 8-16% of the population worldwide. In
developed countries, the most important risk factors for CKD are diabetes,
hypertension, and obesity, calling into question the importance of educating and
acting on lifestyles and nutrition. A balanced diet and supplementation can
indeed support the maintenance of a general health status, including preservation
of renal function, and can help to manage and curb the main risk factors for
renal damage. While the concept of protein and salt restriction in nephrology is
historically acknowledged, the role of some nutrients in renal health and the
importance of nutrition as a preventative measure for renal care are less known.
In this narrative review, we provide an overview of the demonstrated and
potential actions of some selected nutrients, nutraceuticals, and xenobiotics on
renal health and function. The direct and indirect effects of fiber, protein,
fatty acids, curcumin, steviol glycosides, green tea, coffee, nitrates, nitrites,
and alcohol on kidney health are reviewed here. In view of functional and
personalized nutrition, understanding the renal and systemic effects of dietary
components is essential since many chronic conditions, including CKD, are related
to systemic dysfunctions such as chronic low-grade inflammation.
PMID- 29937490
TI - Development of a Fingerprint-Based Scoring Function for the Prediction of the
Binding Mode of Carbonic Anhydrase II Inhibitors.
AB - Carbonic anhydrase II (CAII) is a zinc-containing metalloenzyme whose aberrant
activity is associated with various diseases such as glaucoma, osteoporosis, and
different types of tumors; therefore, the development of CAII inhibitors, which
can represent promising therapeutic agents for the treatment of these
pathologies, is a current topic in medicinal chemistry. Molecular docking is a
commonly used tool in structure-based drug design of enzyme inhibitors. However,
there is still a need for improving docking reliability, especially in terms of
scoring functions, since the complex pattern of energetic contributions driving
ligand-protein binding cannot be properly described by mathematical functions
only including approximated energetic terms. Here we report a novel CAII-specific
fingerprint-based (IFP) scoring function developed according to the ligand
protein interactions detected in the CAII-inhibitor co-crystal structures of the
most potent CAII ligands. Our IFP scoring function outperformed the ability of
Autodock4 scoring function to identify native-like docking poses of CAII
inhibitors and thus allowed a considerable improvement of docking reliability.
Moreover, the ligand-protein interaction fingerprints showed a useful application
in the binding mode analysis of structurally diverse CAII ligands.
PMID- 29937491
TI - Impact of the Familiar Environment in 11-14-Year-Old Minors' Mental Health.
AB - The analysis of the mental health in children under 14 years has become a
research topic of global interest where the family can be a key factor for
protection or risk against mental health problems. With this work, we intend to
determine, employing binary logistic regression analysis, whether parental
acceptance-rejection perceived by boys and girls can predict their mental health.
Seven hundred sixty-two students participated, the average age was 12.23 years;
53.8% (n = 410) girls and 46.2% (n = 352) boys. We have used the Strengths and
Difficulties Questionnaire (SDQ), self-reported version and the Affection Scale
children version (EA-H) for parental acceptance-rejection to assess mental
health. The odds ratio (OR) of the logistic models reports that there is a
greater probability of having mental health problems in boys and girls when they
perceive that they are highly criticized and rejected by their parents. With our
work, we highlight the importance of the environment and family affection on
mental health. The perception of the children about the rejection, aversion, and
criticism of their parents constitutes a risk factor in the manifestation of
mental health problems.
PMID- 29937492
TI - Fat Loss in Continuous Enteral Feeding of the Preterm Infant: How Much, What and
When Is It Lost?
AB - Human milk fat is a concentrated source of energy and provides essential and long
chain polyunsaturated fatty acids. According to previous experiments, human milk
fat is partially lost during continuous enteral nutrition. However, these
experiments were done over relatively short infusion times, and a complete
profile of the lost fatty acids was never measured. Whether this loss happens
considering longer infusion times or if some fatty acids are lost more than
others remain unknown. Pooled breast milk was infused through a feeding tube by a
peristaltic pump over a period of 30 min and 4, 12 and 24 h at 2 mL/h. Adsorbed
fat was extracted from the tubes, and the fatty acid composition was analyzed by
gas chromatography-mass spectrometry. Total fat loss (average fatty acid loss)
after 24 h was 0.6 +/- 0.1%. Total fat loss after 24 h infusion was 0.6 +/- 0.1%
of the total fat infused, although the highest losses occur in the first 30 min
of infusion (13.0 +/- 1.6%). Short-medium chain (0.7%, p = 0.15), long chain
(0.6%, p = 0.56), saturated (0.7%, p = 0.4), monounsaturated (0.5%, p = 0.15),
polyunsaturated fatty (0.7%, p = 0.15), linoleic (0.7%, p = 0.25), and
docosahexaenoic acids (0.6%, p = 0.56) were not selectively adsorbed to the tube.
However, very long chain fatty (0.9%, p = 0.04), alpha-linolenic (1.6%, p = 0.02)
and arachidonic acids (1%, p = 0.02) were selectively adsorbed and, therefore,
lost in a greater proportion than other fatty acids. In all cases, the magnitude
of the loss was clinically low.
PMID- 29937493
TI - Pathogenomics of Endometriosis Development.
AB - For over 100 years, endometriosis, as a chronic, estrogen-dependent,
inflammatory, heritable disease affecting approximately 5-10% of women in
reproductive age has been the focus of clinicians and scientists. In spite of
numerous environmental, genetic, epigenetic, endocrine, and immunological
studies, our knowledge of endometriosis is still fragmentary, and its precise
pathophysiology and pathogenomics remain a mystery. The implementation of new
technologies has provided tremendous progress in understanding the many intrinsic
molecular mechanisms in the development of endometriosis, with progenitor and
stem cells (SCs) of the eutopic endometrium as the starting players and
endometriotic lesions as the final pathomorphological trait. Novel data on the
molecular, genetic, and epigenetic mechanisms of the disease are briefly
outlined. We hypothesize the existence of an endometriosis development genetic
program (EMDP) that governs the origin of endometrium stem cells programmed for
endometriosis (1), their transition (metaplasia) into mesenchymal SCs (2), and
their invasion of the peritoneum and progression to endometriotic lesions (3).
The pros and cons of the recent unifying theory of endometriosis are also
discussed. Complex genomic and epigenetic interactions at different stages of the
endometriosis process result in different forms of the disease, with specific
features and clinical manifestations. The significance of the EMDP in elaborating
a new strategy for endometriosis prediction, prevention, and treatment is
discussed.
PMID- 29937494
TI - Comparative Analysis between the In Vivo Biodistribution and Therapeutic Efficacy
of Adipose-Derived Mesenchymal Stromal Cells Administered Intraperitoneally in
Experimental Colitis.
AB - Mesenchymal stem cells (MSCs) have emerged as a promising treatment for
inflammatory diseases. The immunomodulatory effect of MSCs takes place both by
direct cell-to-cell contact and by means of soluble factors that leads to an
increased accumulation of regulatory immune cells at the sites of inflammation.
Similar efficacy of MSCs has been described regardless of the route of
administration used, the inflammation conditions and the major histocompatibility
complex context. These observations raise the question of whether the migration
of the MSCs to the inflamed tissues is a pre-requisite to achieve their
beneficial effect. To address this, we examined the biodistribution and the
efficacy of intraperitoneal luciferase-expressing human expanded adipose-derived
stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were
stratified according to their response to the Luci-eASC treatment. According to
the stratification criteria, there was a tendency to increase the bioluminescence
signal in the intestine at the expense of a decrease in the bioluminescence
signal in the liver in the “responder” mice. These data thus suggest
that the accumulation of the eASCs to the inflamed tissues is beneficial for
achieving an optimal modulation of inflammation.
PMID- 29937495
TI - Anthocyanins of Coloured Wheat Genotypes in Specific Response to SalStress.
AB - The present study investigated the effect of salt stress on the development of
adaptive responses and growth parameters of different coloured wheat genotypes.
The different coloured wheat genotypes have revealed variation in the anthocyanin
content, which may affect the development of adaptive responses under increasing
salinity stress. In the early stage of treatment with salt at a lower NaCl
concentration (100 mM), anthocyanins and proline accumulate, which shows rapid
development of the stress reaction. A dose-dependent increase in flavonol content
was observed for wheat genotypes with more intense purple-blue pigmentation after
treatment with 150 mM and 200 mM NaCl. The content of Na+ and K+ obtained at
different levels of salinity based on dry weight (DW) was more than 3 times
greater than the control, with a significant increase of both ions under salt
stress. Overall, our results demonstrated that coloured wheat genotypes with high
anthocyanin content are able to maintain significantly higher dry matter
production after salt stress treatment.
PMID- 29937496
TI - Relationship between Physical Activity, Screen Time and Weight Status among Young
Adolescents.
AB - It is well established that lack of physical activity and high bouts of sedentary
behaviour are now associated with all-cause and cardiovascular mortality. The
purpose of this study was to investigate the relationship between physical
activity participation, overall screen time and weight status amongst early Irish
adolescent youth. Participants were a sample of 169 students: 113 boys (mean age
= 12.89 +/- 0.34 years) and 56 girls (mean age = 12.87 +/- 0.61 years). The data
gathered in the present study included physical activity (accelerometry), screen
time (self-report) and anthropometric measurements. Overweight and obese
participants accumulated significantly more minutes of overall screen time daily
compared to their normal-weight counterparts. A correlation between physical
activity and daily television viewing was evident among girls. No significant
interaction was apparent when examining daily physical activity and overall
screen time in the prediction of early adolescents’ body mass index.
Results suggest the importance of reducing screen time in the contribution
towards a healthier weight status among adolescents. Furthermore, physical
activity appears largely unrelated to overall screen time in predicting
adolescent weight status, suggesting that these variables may be independent
markers of health in youth. The existing relationship for girls between moderate
to-vigorous physical activity and time spent television viewing may be a
potential area to consider for future intervention design with adolescent youth.
PMID- 29937497
TI - Phytochemicals: Target-Based Therapeutic Strategies for Diabetic Retinopathy.
AB - Background: A variety of causative factors are involved in the initiation of
diabetic retinopathy (DR). Current antidiabetic therapies are expensive and not
easily accessible by the public. Furthermore, the use of multiple synthetic drugs
leads to severe side effects, which worsen the diabetic patient’s
condition. Medicinal plants and their derived phytochemicals are considered safe
and effective treatment and their consumption can reduce the DR risk. In this
article, we discuss a variety of medicinal plants, and their noteworthy bio
active constituents, that will be utilized as target based therapeutic strategies
for DR. Methods: A broad-spectrum study was conducted using published English
works in various electronic databases including Science Direct, PubMed, Scopus,
and Google Scholar. Results: Targeting the multiple pathological factors
including ROS, AGEs formation, hexosamine flux, PARP, PKC, and MAPK activation
through variety of bioactive constituents in medicinal plants, diabetes
progression can be delayed with improved loss of vision. Conclusions: Data
reveals that traditional herbs and their prominent bioactive components control
and normalize pathological cellular factors involved in DR progression.
Therefore, studies should be carried out to explore the protective retinopathy
effects of medicinal plants using experimental animal and humans models.
PMID- 29937498
TI - Potential Inherent Stimulation of the Innate Immune System by Nucleic Acid
Aptamers and Possible Corrective Approaches.
AB - It is well known that unmethylated 2′-deoxycytidine-phosphate-2′
guanine (CpG) sequences alone or in longer DNA and RNA oligonucleotides can act
like pathogen-associated molecular patterns (PAMPs) and trigger the innate immune
response leading to deleterious cytokine production via Toll-like receptors
(TLRs). Clearly, such CpG or CpG-containing sequences in aptamers intended for
therapy could present very damaging side effects to patients. Previous antisense
oligonucleotide developers were faced with the same basic CpG dilemma and devised
not only avoidance, but other effective strategies from which current aptamer
developers can learn to ameliorate or eliminate damaging CpG effects. These
strategies include obvious methylation of cytosines in the aptamer structure, as
long as it does not affect aptamer binding in vivo, truncation of the aptamer to
its essential binding site, backbone modifications, co-administration of
antagonistic or suppressive oligonucleotides, or other novel drugs under
development to lessen the toxic CpG effect on innate immunity.
PMID- 29937500
TI - On Maximizing the Throughput of Packet Transmission under Energy Constraints.
AB - More and more Internet of Things (IoT) wireless devices have been providing
ubiquitous services over the recent years. Since most of these devices are
powered by batteries, a fundamental trade-off to be addressed is the depleted
energy and the achieved data throughput in wireless data transmission. By
exploiting the rate-adaptive capacities of wireless devices, most existing works
on energy-efficient data transmission try to design rate-adaptive transmission
policies to maximize the amount of transmitted data bits under the energy
constraints of devices. Such solutions, however, cannot apply to scenarios where
data packets have respective deadlines and only integrally transmitted data
packets contribute. Thus, this paper introduces a notion of weighted throughput,
which measures how much total value of data packets are successfully and
integrally transmitted before their own deadlines. By designing efficient rate
adaptive transmission policies, this paper aims to make the best use of the
energy and maximize the weighted throughput. What is more challenging but with
practical significance, we consider the fading effect of wireless channels in
both offline and online scenarios. In the offline scenario, we develop an optimal
algorithm that computes the optimal solution in pseudo-polynomial time, which is
the best possible solution as the problem undertaken is NP-hard. In the online
scenario, we propose an efficient heuristic algorithm based on optimal properties
derived for the optimal offline solution. Simulation results validate the
efficiency of the proposed algorithm.
PMID- 29937499
TI - A Review of Methods for Assessing the Environmental Health Impacts of an
Agricultural System.
AB - (1) Background: Global agricultural production is projected to increase
substantially in the coming decades. Agricultural production provides food and
materials crucial to human survival and well-being and is a critical source of
livelihood, providing employment opportunities and economic benefits. However,
industrialized or intensified agricultural systems, in particular, can have
adverse effects on public health, place pressure on natural resources, and reduce
environmental sustainability. This review attempts to identify and characterize
key environmental health assessment methods for examining a broad array of
potential impacts; (2) Methods: Electronic databases Medline, Scopus, Web of
Science, and GreenLINE were searched for published literature that presented
methods for conducting an environmental health assessment of an agricultural
system; (3) Results: Fifty-three sources were included in the review. Eight
methods were selected to illustrate the wide range of approaches currently
available: health risk assessment methods, health impact assessment,
environmental impact assessment methods, environmental burden of disease,
lifecycle methods, integrated assessment modeling, trade-off analysis, and
economic assessment; (4) Conclusions: This review can provide guidance for
selecting an existing method or for designing a new method for assessing the
environmental health impacts of an agricultural system.
PMID- 29937501
TI - The Changes in the Morphology of Bi-Sb System under Centrifugal Force at Room
Temperature.
AB - In this paper, the morphology evolution in a Bi-Sb system under the centrifugal
force at room temperature is discussed. The rotation speed was 35,000 rotations
per minute and the length of the arm (radii) was 88 mm. It is shown, that after
the centrifugation the phases become oriented in the direction parallel to the
direction of the centrifugal force. Moreover, the voids move in the direction
opposite to the centrifugal force direction. The movements of such voids result
in their coalescence and finally lead to formation of cracks at the interface
between ordered and disordered part of the sample.
PMID- 29937502
TI - Rectification of Images Distorted by Microlens Array Errors in Plenoptic Cameras.
AB - A plenoptic cameras is a sensor that records the 4D light-field distribution of
target scenes. The surface errors of a microlens array (MLA) can cause the
degradation and distortion of the raw image captured by a plenoptic camera,
resulting in the confusion or loss of light-field information. To address this
issue, we propose a method for the local rectification of distorted images using
white light-field images. The method consists of microlens center calibration,
geometric rectification, and grayscale rectification. The scope of its
application to different sized errors and the rectification accuracy of three
basic surface errors, including the overall accuracy and the local accuracy, are
analyzed through simulation of imaging experiments. The rectified images have a
significant improvement in quality, demonstrating the provision of precise light
field data for reconstruction of real objects.
PMID- 29937503
TI - The Direct Involvement of Dark-Induced Tic55 Protein in Chlorophyll Catabolism
and Its Indirect Role in the MYB108-NAC Signaling Pathway during Leaf Senescence
in Arabidopsis thaliana.
AB - The chloroplast relies on proteins encoded in the nucleus, synthesized in the
cytosol and subsequently transported into chloroplast through the protein
complexes Toc and Tic (Translocon at the outer/inner membrane of chloroplasts). A
Tic complex member, Tic55, contains a redox-related motif essential for protein
import into chloroplasts in peas. However, Tic55 is not crucial for protein
import in Arabidopsis. Here, a tic55-II-knockout mutant of Arabidopsis thaliana
was characterized for Tic55 localization, its relationship with other translocon
proteins, and its association with plant leaf senescence when compared to the
wild type. Individually darkened leaves (IDLs) obtained through dark-induced leaf
senescence were used to demonstrate chlorophyll breakdown and its relationship
with plant senescence in the tic55-II-knockout mutant. The IDLs of the tic55-II
knockout mutant contained higher chlorophyll concentrations than those of the
wild type. Our microarray analysis of IDLs during leaf senescence identified
seven senescence-associated genes (SAGs) that were downregulated in the tic55-II
knockout mutant: ASP3, APG7, DIN2, DIN11, SAG12, SAG13, and YLS9. Real-time
quantitative PCR confirmed the reliability of microarray analysis by showing the
same expression patterns with those of the microarray data. Thus, Tic55 functions
in dark-induced aging in A. thaliana by indirectly regulating downstream SAGs
expression. In addition, the expression of four NAC genes, including ANAC003,
ANAC010, ANAC042, and ANAC075 of IDL treated tic55-II-knockout mutant appeared to
be downregulated. Yeast one hybrid assay revealed that only ANAC003 promoter
region can be bound by MYB108, suggesting that a MYB-NAC regulatory network is
involved in dark-stressed senescence.
PMID- 29937504
TI - Dietary Micronutrient and Mineral Intake in the Mediterranean Healthy Eating,
Ageing, and Lifestyle (MEAL) Study.
AB - BACKGROUND: Dietary vitamins and minerals are essential compounds for the proper
functioning of metabolic enzymes, regulation of gene transcription, and powering
the body’s defense against oxidative stress. The aim of the present study
was to investigate micronutrient consumption separately by age and sex, major
dietary sources, and percentage of individuals meeting the recommended
requirements according to Italian (Livelli di Assunzione di Riferimento di
Nutrienti (LARN)) and European (European Food Safety Agency (EFSA)) agencies.
METHODS: Data were obtained from the Mediterranean Healthy Eating, Ageing, and
Lifestyle (MEAL) study, which included a sample of 1838 individuals randomly
collected in the city of Catania, southern Italy. A validated food frequency
questionnaire was used to collect information on diet. RESULTS: Intake of vitamin
A, vitamin C, and vitamin B group (except vitamin B9) was in line with other
reports and was adequate according to the guidelines, while the percentage of
individuals meeting the guidelines for vitamin D, vitamin E, and vitamin B9 was
about 3%, 10%, and 40%, respectively. Among minerals, intake of iron, magnesium,
and selenium was adequate for most of the sample, while the percentage of
individuals meeting the recommendations for calcium, sodium, and potassium intake
was about 20%, 8%, and 35%, respectively. CONCLUSIONS: An important percentage of
the population would benefit from campaigns raising awareness of micronutrient
deficiency or excessive consumption potentially affecting their health.
PMID- 29937505
TI - Pair Distribution Function Analysis of ZrO2 Nanocrystals and Insights in the
Formation of ZrO2-YBa2Cu3O7 Nanocomposites.
AB - The formation of superconducting nanocomposites from preformed nanocrystals is
still not well understood. Here, we examine the case of ZrO2 nanocrystals in a
YBa2Cu3O7−x matrix. First we analyzed the preformed ZrO2 nanocrystals via
atomic pair distribution function analysis and found that the nanocrystals have a
distorted tetragonal crystal structure. Second, we investigated the influence of
various surface ligands attached to the ZrO2 nanocrystals on the distribution of
metal ions in the pyrolyzed matrix via secondary ion mass spectroscopy technique.
The choice of stabilizing ligand is crucial in order to obtain good
superconducting nanocomposite films with vortex pinning. Short, carboxylate based
ligands lead to poor superconducting properties due to the inhomogeneity of metal
content in the pyrolyzed matrix. Counter-intuitively, a phosphonate ligand with
long chains does not disturb the growth of YBa2Cu3O7−x. Even more
surprisingly, bisphosphonate polymeric ligands provide good colloidal stability
in solution but do not prevent coagulation in the final film, resulting in poor
pinning. These results thus shed light on the various stages of the
superconducting nanocomposite formation.
PMID- 29937506
TI - A Dual-Channel Supply Chain Coordination under Carbon Cap-and-Trade Regulation.
AB - We consider a dual-channel supply chain coordination under a carbon cap-and-trade
regulation. The dual-channel refers to the traditional retail channel and the
network direct channel, and both two channels' selling prices can affect the
market demand. We formulate the problem as a supplier-Stackelberg game model and
obtain the optimal pricing decisions and corresponding profits in centralized and
decentralized systems. We explore the effects of cap-and-trade regulation on
optimal decisions and profits. To improve the performance of the decentralized
system, we propose online channel price discount and offline channel price
discount contracts to coordinate dual-channel supply chain and provide a transfer
payment mechanism to make win-win of both sides. Moreover, we investigate how
carbon regulation affects the coordination performance. Numerical examples
illustrate the process to find the appropriate price discount coefficient and
show the coordination effects of two contracts.
PMID- 29937507
TI - Modeling and Characterization of Traffic Flows in Urban Environments.
AB - Currently, one of the main challenges faced in large metropolitan areas is
traffic congestion. To address this problem, adequate traffic control could
produce many benefits, including reduced pollutant emissions and reduced travel
times. If it were possible to characterize the state of traffic by predicting
future traffic conditions for optimizing the route of automated vehicles, and if
these measures could be taken to preventively mitigate the effects of congestion
with its related problems, the overall traffic flow could be improved. This paper
performs an experimental study of the traffic distribution in the city of
Valencia, Spain, characterizing the different streets of the city in terms of
vehicle load with respect to the travel time during rush hour traffic conditions.
Experimental results based on realistic vehicular traffic traces from the city of
Valencia show that only some street segments fall under the general theory of
vehicular flow, offering a good fit using quadratic regression, while a great
number of street segments fall under other categories. Although in some cases
such discrepancies are related to lack of traffic, injecting additional vehicles
shows that significant mismatches still persist. Thus, in this paper we propose
an equation to characterize travel times over a segment belonging to the sigmoid
family; specifically, we apply logistic regression, being able to significantly
improve the curve fitting results for most of the street segments under analysis.
Based on our regression results, we performed a clustering analysis of the
different street segments, showing that they can be classified into three well
defined categories, which evidences a predictable traffic distribution using the
logistic regression throughout the city during rush hours, and allows optimizing
the traffic for automated vehicles.
PMID- 29937508
TI - An Environmental Management Maturity Model of Construction Programs Using the AHP
Entropy Approach.
AB - The accelerating process of urbanization in China has led to considerable
opportunities for the development of construction projects, however,
environmental issues have become an important constraint on the implementation of
these projects. To quantitatively describe the environmental management
capabilities of such projects, this paper proposes a 2-dimensional Environmental
Management Maturity Model of Construction Program (EMMMCP) based on an analysis
of existing projects, group management theory and a management maturity model. In
this model, a synergetic process was included to compensate for the lack of
consideration of synergies in previous studies, and it was involved in the
construction of the first dimension, i.e., the environmental management index
system. The second dimension, i.e., the maturity level of environment management,
was then constructed by redefining the hierarchical characteristics of
construction program (CP) environmental management maturity. Additionally, a
mathematical solution to this proposed model was derived via the Analytic
Hierarchy Process (AHP)-entropy approach. To verify the effectiveness and
feasibility of this proposed model, a computational experiment was conducted, and
the results show that this approach could not only measure the individual levels
of different processes, but also achieve the most important objective of
providing a reference for stakeholders when making decisions on the environmental
management of construction program, which reflects this model is reasonable for
evaluating the level of environmental management maturity in CP. To our
knowledge, this paper is the first study to evaluate the environmental management
maturity levels of CP, which would fill the gap between project program
management and environmental management and provide a reference for relevant
management personnel to enhance their environmental management capabilities.
PMID- 29937509
TI - Mental Health Literacy in Young Adults: Adaptation and Psychometric Properties of
the Mental Health Literacy Questionnaire.
AB - Mental health literacy (MHL) is considered a prerequisite for early recognition
and intervention in mental disorders, and for this reason, it has become a focus
of research over the past few decades. Assessing this construct is relevant for
identifying knowledge gaps and erroneous beliefs concerning mental health issues,
to inform the development of interventions aimed at promoting mental health
literacy as well as the evaluation of these interventions. Recently, we developed
a new self-reporting measure (MHLq) for assessing mental health literacy in young
people (12-14 years-old), meeting the need to assess MHL from a comprehensive
perspective of the construct instead of focusing on a restricted number of mental
disorders or specific dimensions (e.g., knowledge concerning specific disorders;
stigma). The present study aimed to adapt the MHLq for the young adult population
and to examine its psychometric properties, according to the following steps: (1)
item adaptation, using a think aloud procedure (n = 5); (2) data collection (n =
356, aged between 18 and 25 years old; and (3) psychometric analyses (exploratory
factor analysis and internal consistency analysis). The final version of the
questionnaire included 29 items (total scale α = 0.84), organized by four
dimensions: (1) knowledge of mental health problems (α = 0.74); (2)
erroneous beliefs/stereotypes (α = 0.72); (3) help-seeking and first aid
skills (α = 0.71); and (4) self-help strategies (α = 0.60). The
results suggest that the MHLq-adult form is a practical, valid, and reliable
screening tool for identifying gaps in knowledge, beliefs, and behavioral
intentions related to mental health and mental disorders, planning promotion
programs, and evaluating intervention effectiveness.
PMID- 29937510
TI - Rural Households' Livelihood Capital, Risk Perception, and Willingness to
Purchase Earthquake Disaster Insurance: Evidence from Southwestern China.
AB - Earthquake disaster insurance can effectively reduce the impact of earthquake
disasters on rural households. Exploring rural households’ willingness to
purchase earthquake disaster insurance in earthquake disaster areas provides an
understanding of the motivations underlying the implementation of an insurance
policy. However, few studies have examined the perspectives of rural households,
in order to explore the correlations between the rural households’
livelihood capital, their disaster risk perception, and their willingness to
purchase earthquake disaster insurance. A cross-sectional survey data including
241 rural households from the most severe disaster counties (cities) during the 5
• 12 Wenchuan earthquake was examined with regard to rural households’
livelihood and disaster risk perception, and ordinal logistic regression models
were constructed to explore rural households’ willingness to purchase
earthquake disaster insurance, as well as the driving mechanism behind this
willingness. The results showed that 34.44% of rural households were very willing
to purchase earthquake disaster insurance, and 7.05% of rural households were
very reluctant to purchase earthquake insurance. Rural households’
livelihood capital and risk perceptions were the most important factors affecting
their willingness to purchase earthquake disaster insurance. Rural households
with higher scores on natural capital, physical capital, possibility, and worry
were more likely to purchase earthquake disaster insurance. Specifically, keeping
all other variables constant, every one unit increase in nature capital and
physical capital corresponded to an increase in the odds of willingness to
purchase earthquake disaster insurance by a factor of 0.14 and 0.06,
respectively; every one unit increase in possibility and worry corresponded to an
increase in the odds of willingness to purchase earthquake disaster insurance by
a factor of 0.03 and 0.04, respectively. This study contributes to the current
literature by increasing the understanding of the relationships between Chinese
rural households’ livelihood capital and risk perceptions, and their
willingness to purchase earthquake disaster insurance.
PMID- 29937512
TI - A Fast and Robust Non-Sparse Signal Recovery Algorithm for Wearable ECG
Telemonitoring Using ADMM-Based Block Sparse Bayesian Learning.
AB - Wearable telemonitoring of electrocardiogram (ECG) based on wireless body Area
networks (WBAN) is a promising approach in next-generation patient-centric
telecardiology solutions. In order to guarantee long-term effective operation of
monitoring systems, the power consumption of the sensors must be strictly
limited. Compressed sensing (CS) is an effective method to alleviate this
problem. However, ECG signals in WBAN are usually non-sparse, and most
traditional compressed sensing recovery algorithms have difficulty recovering non
sparse signals. In this paper, we proposed a fast and robust non-sparse signal
recovery algorithm for wearable ECG telemonitoring. In the proposed algorithm,
the alternating direction method of multipliers (ADMM) is used to accelerate the
speed of block sparse Bayesian learning (BSBL) framework. We used the famous MIT
BIH Arrhythmia Database, MIT-BIH Long-Term ECG Database and ECG datasets
collected in our practical wearable ECG telemonitoring system to verify the
performance of the proposed algorithm. The experimental results show that the
proposed algorithm can directly recover ECG signals with a satisfactory accuracy
in a time domain without a dictionary matrix. Due to acceleration by ADMM, the
proposed algorithm has a fast speed, and also it is robust for different ECG
datasets. These results suggest that the proposed algorithm is very promising for
wearable ECG telemonitoring.
PMID- 29937511
TI - Antiproliferative and Antimicrobial Activities of Selected Bryophytes.
AB - One-hundred and sixty-eight aqueous and organic extracts of 42 selected bryophyte
species were screened in vitro for antiproliferative activity on a panel of human
gynecological cancer cell lines containing HeLa (cervix epithelial
adenocarcinoma), A2780 (ovarian carcinoma), and T47D (invasive ductal breast
carcinoma) cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay and for antibacterial activity on 11 strains using the disc
diffusion method. A total of 99 extracts derived from 41 species exerted ≥25%
inhibition of proliferation of at least one of the cancer cell lines at 10
μg/mL. In the cases of Brachythecium rutabulum, Encalypta streptocarpa,
Climacium dendroides, Neckera besseri, Pleurozium schreberi, and Pseudoleskeella
nervosa, more than one extract was active in the antiproliferative assay, whereas
the highest activity was observed in the case of Paraleucobryum longifolium. From
the tested families, Brachytheciaceae and Amblystegiaceae provided the highest
number of antiproliferative extracts. Only 19 samples of 15 taxa showed moderate
antibacterial activity, including the most active Plagiomnium cuspidatum, being
active on 8 tested strains. Methicillin-resistant Staphylococcus aureus (MRSA)
and Staphylococcus aureus were the most susceptible to the assayed species. This
is the first report on the bioactivities of these 14 species.
PMID- 29937513
TI - Identification of an Actionable Mutation of KIT in a Case of Extraskeletal Myxoid
Chondrosarcoma.
AB - Extraskeletal myxoid chondrosarcoma (EMC) is an extremely rare soft tissue
sarcoma, marked by a translocation involving the NR4A3 gene. EMC is usually
indolent and moderately sensitive to anthracycline-based chemotherapy. Recently,
we reported on the therapeutic activity of sunitinib in a series of EMC cases,
however the molecular target of sunitinib in EMC is unknown. Moreover, there is
still the need to identify alternative therapeutic strategies. To better
characterize this disease, we performed whole transcriptome sequencing in five
EMC cases. Peculiarly, in one sample, an in-frame deletion (c.1735_1737delGAT
p.D579del) was identified in exon 11 of KIT. The deletion was somatic and
heterozygous and was validated both at DNA and mRNA level. This sample showed a
marked high expression of KIT at the mRNA level and a mild phosphorylation of the
receptor. Sanger sequencing of KIT in additional 15 Formalin Fixed Paraffin
Embedded (FFPE) EMC did not show any other mutated cases. In conclusion, exon 11
KIT mutation was detected only in one out of 20 EMC cases analyzed, indicating
that KIT alteration is not a recurrent event in these tumors and cannot explain
the EMC sensitivity to sunitinib, although it is an actionable mutation in the
individual case in which it has been identified.
PMID- 29937514
TI - Boron: Functions and Approaches to Enhance Its Availability in Plants for
Sustainable Agriculture.
AB - Boron (B) is an essential trace element required for the physiological
functioning of higher plants. B deficiency is considered as a nutritional
disorder that adversely affects the metabolism and growth of plants. B is
involved in the structural and functional integrity of the cell wall and
membranes, ion fluxes (H+, K+, PO43−, Rb+, Ca2+) across the membranes, cell
division and elongation, nitrogen and carbohydrate metabolism, sugar transport,
cytoskeletal proteins, and plasmalemma-bound enzymes, nucleic acid, indoleacetic
acid, polyamines, ascorbic acid, and phenol metabolism and transport. This review
critically examines the functions of B in plants, deficiency symptoms, and the
mechanism of B uptake and transport under limited B conditions. B deficiency can
be mitigated by inorganic fertilizer supplementation, but the deleterious impact
of frequent fertilizer application disrupts soil fertility and creates
environmental pollution. Considering this, we have summarized the available
information regarding alternative approaches, such as root structural
modification, grafting, application of biostimulators (mycorrhizal fungi (MF) and
rhizobacteria), and nanotechnology, that can be effectively utilized for B
acquisition, leading to resource conservation. Additionally, we have discussed
several new aspects, such as the combination of grafting or MF with
nanotechnology, combined inoculation of arbuscular MF and rhizobacteria,
melatonin application, and the use of natural and synthetic chelators, that
possibly play a role in B uptake and translocation under B stress conditions.
PMID- 29937515
TI - Role of T-Helper 9 Cells in Chronic Hepatitis C-Infected Patients.
AB - Hepatitis C virus is a hepatotropic virus that is transmitted parenterally. Viral
infections are usually associated with modulations of the immune cells, leading
to enhanced viral survival and spreading, and accordingly, life-threatening
complications. Recently, it has been proposed that a new subset of T-helper,
named T-helper 9, is involved in the pathogenesis of different immunopathological
conditions, such as allergies, tumors, and viral infections. Some studies
reported a protective role, and others described a pathogenic potential for the T
helper 9 cells. Here, we present evidence that T-helper 9 cells are dynamically
increased with increasing the pathogenic strategy for hepatitis C virus (HCV).
Furthermore, viral clearance is associated with a decrease in T-helper 9. The
increase in T-helper 9 was paralleled with an increase in its receptor
expression. Taken together, our data suggest that T-helper 9 cells play an
important role in the pathogenesis of HCV, and is directly associated with HCV
related complications.
PMID- 29937516
TI - Assessment of the Acute and Subchronic Toxicity and Mutagenicity of Sideritis
scardica Griseb. Extracts.
AB - Sideritis scardica Griseb. has a long history of collection from the wild as a
traditional remedy for respiratory and gastrointestinal complaints. It has also
been investigated for its promising pharmacological activities in the central
nervous system. However, its toxicological data is entirely missing. This study
investigated the acute and repeated-dose oral toxicity of a S. scardica 20% (v/v)
ethanol extract in Sprague Dawley rats, and mutagenicity using the Ames test. No
gross pathological abnormalities and no toxicity signs or mortality were detected
in animals treated with the dose of 2000 mg/kg bw during 14 days of observation.
The tested extract was assigned to category 5 of the GHS. To evaluate a repeated
dose toxicity, an extract has been tested over a 28-day period followed by a 14
day recovery period. No mortality and no changes in body/organ weight or food
consumption have been observed. The no-observed-adverse-effect-level of the
extract was determined at 1000 mg/kg bw. The results of Ames tests conducted on
extracts of different polarity (water; 20% (v/v) ethanol; 50% (v/v) ethanol; n
heptane), were unequivocally negative. The study reveals no toxicity of S.
scardica and no concerns for its mutagenic effects, supports its positive safety
profile, and confirms the acknowledged traditional medicinal use in human.
PMID- 29937517
TI - Synthesis of Mesoporous gamma-Al2O3 with Spongy Structure: In-Situ Conversion of
Metal-Organic Frameworks and Improved Performance as Catalyst Support in
Hydrodesulfurization.
AB - Over the past decades, extensive efforts have been devoted to modulating the
textural properties, morphology and microstructure of γ-Al2O3, since the
physiochemical properties of γ-Al2O3 have close correlations with the
performance of hydrotreating catalysts. In this work, a spongy mesoporous γ
alumina (γ-Al2O3) was synthesized using Al-based metal-organic frameworks
(Al-MOFs) as precursor by two-step pyrolysis, and this Al-MOF-derived γ
Al2O3 was used as hydrodesulfurization (HDS) catalyst support, to explore the
effect of support on the HDS performance. Compared with industrial γ-Al2O3,
the spongy alumina displayed well-developed porosity with relatively high surface
area, large pore volume, and abundant weak Lewis acid sites. Based on catalyst
characterization and performance evaluation, sulfurized molybdenum and cobalt
molecules were able to incorporate and highly disperse into channels of the
spongy mesoporous alumina, increasing the dispersion of active catalytic species.
The spongy γ-Al2O3 was also able to enhance the diffusion efficiency and
mass transfer of reactant molecules due to its improved texture properties.
Therefore, the corresponding catalyst presented higher activities toward HDS of
dibenzothiophene (DBT) than that from industrial alumina. The spongy mesoporous
γ-alumina synthesized by Al-MOFs provides a new alternative to further
develop novel γ-alumina materials with different texture and various
nanoporous structures, considering the diversity of MOFs with different
compositions, topological structures, and morphology.
PMID- 29937520
TI - A Context-Aware Edge-Based VANET Communication Scheme for ITS.
AB - We propose a context-aware edge-based packet forwarding scheme for vehicular
networks. The proposed scheme employs a fuzzy logic-based edge node selection
protocol to find the best edge nodes in a decentralized manner, which can achieve
an efficient use of wireless resources by conducting packet forwarding through
edges. A reinforcement learning algorithm is used to optimize the last two-hop
communications in order to improve the adaptiveness of the communication routes.
The proposed scheme selects different edge nodes for different types of
communications with different context information such as connection-dependency
(connection-dependent or connection-independent), communication type (unicast or
broadcast), and packet payload size. We launch extensive simulations to evaluate
the proposed scheme by comparing with existing broadcast protocols and unicast
protocols for various network conditions and traffic patterns.
PMID- 29937518
TI - The Cyanobacterial Ribosomal-Associated Protein LrtA from Synechocystis sp. PCC
6803 Is an Oligomeric Protein in Solution with Chameleonic Sequence Properties.
AB - The LrtA protein of Synechocystis sp. PCC 6803 intervenes in cyanobacterial post
stress survival and in stabilizing 70S ribosomal particles. It belongs to the
hibernating promoting factor (HPF) family of proteins, involved in protein
synthesis. In this work, we studied the conformational preferences and stability
of isolated LrtA in solution. At physiological conditions, as shown by
hydrodynamic techniques, LrtA was involved in a self-association equilibrium. As
indicated by Nuclear Magnetic Resonance (NMR), circular dichroism (CD) and
fluorescence, the protein acquired a folded, native-like conformation between pH
6.0 and 9.0. However, that conformation was not very stable, as suggested by
thermal and chemical denaturations followed by CD and fluorescence. Theoretical
studies of its highly-charged sequence suggest that LrtA had a Janus sequence,
with a context-dependent fold. Our modelling and molecular dynamics (MD)
simulations indicate that the protein adopted the same fold observed in other
members of the HPF family (β-α-β-β-β-α) at its N
terminal region (residues 1-100), whereas the C terminus (residues 100-197)
appeared disordered and collapsed, supporting the overall percentage of overall
secondary structure obtained by CD deconvolution. Then, LrtA has a chameleonic
sequence and it is the first member of the HPF family involved in a self
association equilibrium, when isolated in solution.
PMID- 29937519
TI - Natural Product-Based Pesticide Discovery: Design, Synthesis and Bioactivity
Studies of N-Amino-Maleimide Derivatives.
AB - Natural products are an important source of pesticide discovery. A series of N
amino-maleimide derivatives containing hydrazone group were designed and
synthesized based on the structure of linderone and methyllinderone which were
isolated from Lindera erythrocarpa Makino. According to the bioassay results,
compounds 2 and 3 showed 60% inhibition against mosquito (Culex pipiens pallens)
at 0.25 µg·mL−1. Furthermore, the results of antifungal tests
indicated that most compounds exhibited much better antifungal activities against
fourteen phytopathogenic fungi than linderone and methyllinderone and some
compounds exhibited better antifungal activities than commercial fungicides
(carbendazim and chlorothalonil) at 50 µg·mL−1. In particular,
compound 12 exhibited broad-spectrum fungicidal activity (>50% inhibitory
activities against 11 phytopathogenic fungi) and compounds 12 and 14 displayed
60.6% and 47.9% inhibitory activity against Rhizoctonia cerealis at 12.5
µg·mL−1 respectively. Furthermore, compound 17 was
synthesized, which lacks N-substituent at maleimide and its poor antifungal
activity against Sclerotinia sclerotiorum and Rhizoctonia cerealis at 50
µg·mL−1 showed that the backbone structure of N-amino
maleimide derivatives containing hydrazone group was important to the antifungal
activity.
PMID- 29937521
TI - Thermal Failure Analysis of Fiber-Reinforced Silica Aerogels under Liquid
Nitrogen Thermal Shock.
AB - Aerogel materials are recognized as promising candidates for the thermal
insulator and have achieved great successes for the aerospace applications.
However, the harsh environment on the exoplanet, especially for the tremendous
temperature difference, tends to affect the tenuous skeleton and performances of
the aerogels. In this paper, an evaluation method was proposed to simulate the
environment of exoplanet and study the influence on the fiber-reinforced silica
aerogels with different supercritical point drying (SPD) technology. Thermal
conductivity, mechanical property and the microstructure were characterized for
understanding the thermal failure mechanism. It was found that structure and
thermal property were significantly influenced by the adsorbed water in the
aerogels under the thermal shocks. The thermal conductivity of CO2-SPD aerogel
increased 35.5% after the first shock and kept in a high value, while that of the
ethanol-SPD aerogel increased only 19.5% and kept in a relatively low value. Pore
size distribution results showed that after the first shock the peak pore size of
the CO2-SPD aerogel increased from 18 nm to 25 nm due to the shrinkage of the
skeleton, while the peak pore size of the ethanol-SPD aerogel kept at ~9 nm
probably induced by the spring-back effect. An 80 °C treatment under vacuum
was demonstrated to be an effective way for retaining the good performance of
ethanol-SPD aerogels under the thermal shock. The thermal conductivity increases
of the ethanol-SPD aerogels after 5 shocks decreased from ~30 to ~0% via vacuum
drying, while the increase of the CO2-SPD aerogels via the same treatments
remains ~28%. The high-strain hardening and low-strain soften behaviors further
demonstrated the skeleton shrinkage of the CO2-SPD aerogel.
PMID- 29937523
TI - Management of Cleft Palate in Puppies Using A Temporary Prosthesis: A Report of
Three Cases.
AB - Cleft palate in dogs is a congenital defect that mostly leads to euthanasia of
the affected puppy. If an attempt is made to raise the puppy, it is generally fed
via an orogastric tube. Here, we describe the management of cleft palate in three
puppies (two Boxers, one Collie) using a customised temporary prosthesis, which
allowed the puppies to be bottle-fed and successfully raised by their owners
(Cases 2 and 3) and the author (Case 1). The temporary palatal prosthesis was
manufactured from a mouthguard intended for human children, which is made of
thermoplastic silicone. The preparation procedure was simple and cost-effective.
All puppies underwent corrective surgery at 5-6 months of age. After surgery, one
of the Boxer puppies showed mandibular mesioclusion, while the other two showed
no aberrations. All puppies gained the same amount of weight as their
littermates, although the weight gain of the two Boxers was slower than that of
their littermates. In summary, this case report describes an easy and effective
way to raise puppies with cleft palate until corrective surgery can be performed.
PMID- 29937522
TI - Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring
Disease Burden in Extramedullary Multiple Myeloma.
AB - Mutational characterisation in extramedullary multiple myeloma (EM-MM) patients
is challenging due to inaccessible EM plasmacytomas, unsafe nature of multiple
biopsies and the spatial and temporal genomic heterogeneity apparent in MM
(Graphical abstract). Conventional monitoring of disease burden is through serum
markers and PET-CT, however these modalities are sometimes inadequate (serum
markers), not performed in a timely manner (PET-CT) and uninformative for
identifying mutations driving disease progression. DNA released into the blood by
tumour cells (ctDNA) contains the predominant clones derived from the multiple
disease foci. Blood-derived ctDNA can, therefore, provide a holistic illustration
of the major drivers of disease progression. In this report, the utility of
ctDNA, as an adjunct to currently available modalities in EM-MM, is presented for
a patient with EM and oligosecretory (OS) disease. Whole exome sequencing of
contemporaneously acquired tumour tissue and matched ctDNA samples revealed the
presence of spatial and temporal genetic heterogeneity and the identification of
pathways associated with drug resistance. Longitudinal monitoring of plasma
samples revealed that ctDNA can be utilised to define the dynamic clonal
evolution co-existent with disease progression and as an adjunct non-invasive
marker of tumour burden.
PMID- 29937524
TI - Genipin-Enhanced Fibrin Hydrogel and Novel Silk for Intervertebral Disc Repair in
a Loaded Bovine Organ Culture Model.
AB - (1) Background: Intervertebral disc (IVD) repair represents a major challenge.
Using functionalised biomaterials such as silk combined with enforced hydrogels
might be a promising approach for disc repair. We aimed to test an IVD repair
approach by combining a genipin-enhanced fibrin hydrogel with an engineered silk
scaffold under complex load, after inducing an injury in a bovine whole organ IVD
culture; (2) Methods: Bovine coccygeal IVDs were isolated from ~1-year-old
animals within four hours post-mortem. Then, an injury in the annulus fibrosus
was induced by a 2 mm biopsy punch. The repair approach consisted of genipin
enhanced fibrin hydrogel that was used to fill up the cavity. To seal the injury,
a Good Manufacturing Practise (GMP)-compliant engineered silk fleece-membrane
composite was applied and secured by the cross-linked hydrogel. Then, IVDs were
exposed to one of three loading conditions: no load, static load and complex load
in a two-degree-of-freedom bioreactor for 14 days. Followed by assessing DNA and
matrix content, qPCR and histology, the injured discs were compared to an
uninjured control IVD that underwent the same loading profiles. In addition, the
genipin-enhanced fibrin hydrogel was further investigated with respect to
cytotoxicity on human stem cells, annulus fibrosus, and nucleus pulposus cells;
(3) Results: The repair was successful as no herniation could be detected for any
of the three loading conditions. Disc height was not recovered by the repair DNA
and matrix contents were comparable to a healthy, untreated control disc. Genipin
resulted being cytotoxic in the in vitro test but did not show adverse effects
when used for the organ culture model; (4) Conclusions: The current study
indicated that the combination of the two biomaterials, i.e., genipin-enhanced
fibrin hydrogel and an engineered silk scaffold, was a promising approach for IVD
repair. Furthermore, genipin-enhanced fibrin hydrogel was not suitable for cell
cultures; however, it was highly applicable as a filler material.
PMID- 29937526
TI - Risk Factors for Ventricular Septal Defects in Murmansk County, Russia: A
Registry-Based Study.
AB - Cardiovascular malformations are one of the most common birth defects among
newborns and constitute a leading cause of perinatal and infant mortality.
Although some risk factors are recognized, the causes of cardiovascular
malformations (CVMs) remain largely unknown. In this study, we aim to identify
risk factors for ventricular septal defects (VSDs) in Northwest Russia. The study
population included singleton births registered in the Murmansk County Birth
Registry (MCBR) between 1 January 2006 and 31 December 2011. Infants with a
diagnosis of VSD in the MCBR and/or in the Murmansk Regional Congenital Defects
Registry (up to two years post-delivery) constituted the study sample. Among the
52,253 infants born during the study period there were 744 cases of septal heart
defects (SHDs), which corresponds to a prevalence of 14.2 [95% confidence
interval (CI) of 13.2-15.3] per 1000 infants. Logistic regression analyses were
carried out to identify VSD risk factors. Increased risk of VSDs was observed
among infants born to mothers who abused alcohol [OR = 4.83; 95% CI 1.88-12.41],
or smoked during pregnancy [OR = 1.35; 95% CI 1.02-1.80]. Maternal diabetes
mellitus was also a significant risk factor [OR = 8.72; 95% CI 3.16-24.07], while
maternal age, body mass index, folic acid and multivitamin intake were not
associated with increased risk. Overall risks of VSDs for male babies were lower
[OR = 0.67; 95% CI 0.52-0.88].
PMID- 29937527
TI - Combined Use of C. butyricum Sx-01 and L. salivarius C-1-3 Improves Intestinal
Health and Reduces the Amount of Lipids in Serum via Modulation of Gut Microbiota
in Mice.
AB - The study was conducted to investigate whether combined use of C. butyricum Sx-01
and L. salivarius C-1-3 could improve the intestinal health and reduce the lipid
levels in sera of mice and whether these benefits were related to regulating the
intestinal microflora. Eighty Kunming male mice were divided into four groups
with five replicates per group and four mice per replicate. Mice in the control
group were administrated with 0.2 mL normal saline; mice in three experimental
groups were daily orally administrated with 4 × 108 cfu of L. salivarius, 4
× 108 cfu of C. butyricum, and a combination thereof (2 × 108 cfu of
L. salivarius, and 2 × 108 cfu of C. butyricum), respectively. The
experiment lasted for 14 days. The results showed that the average daily feed
intake (ADFI) and feed/gain (F/G) ratio of growing mice underwent no significant
changes (p > 0.05); however, the average daily gain (ADG) tended to increase over
short periods of time. The activities of SOD and GSH-Px in serum in the
combination group were significantly increased (p < 0.05); The triglyceride, and
total cholesterol, contents in serum in the combined treatment group were
significantly decreased (p < 0.05); The total volatile fatty acids and butyric
acid in faecal matter of mice in the experimental groups were all significantly
increased at 14 days (p < 0.05); The length of villi, and the mucosal thickness
of colon and caecum (p < 0.05) were significantly improved; The relative
abundance of some bacteria with antioxidant capacity or decomposing cholesterol
capacity or butyrate producing capacity was increased, while the relative
abundance of some pathogenic bacteria was decreased in the colon. Furthermore,
our results showed that the beneficial effects of the combined use of the two
strains was higher than that of single use. Overall, the results demonstrated
that the combined use of C. butyricum Sx-01 and L. salivarius C-1-3 can
significantly improve intestinal health and reduce the amount of lipids in sera
of mice. The reason for these effects might be that besides their own probiotic
effects, combined use of the two strains could regulate the intestinal
microflora.
PMID- 29937528
TI - Removal Behavior of Methylene Blue from Aqueous Solution by Tea Waste: Kinetics,
Isotherms and Mechanism.
AB - Tea waste (biosorbent) was characterized by BET, SEM, FTIR, XPS, solid state 13C
NMR and applied to remove methylene blue (MB) from aqueous solution. The effect
of different factors on MB removal, kinetics, isotherms and potential mechanism
was investigated. The results showed that tea waste contains multiple organic
functional groups. The optimum solid-to-liquid ratio for MB adsorption was 4.0
g·L−1 and the initial pH of the MB solution did not need to be
adjusted to a certain value. The pseudo-second-order model could well fit the
adsorption kinetic process. The adsorption process could be divided into two
stages: a fast adsorption stage and a slow adsorption stage. The adsorption
isotherm could be well described by Langmuir and Temkin isotherm models. The
maximum adsorption amount could reach 113.1461 mg·g−1 based on
Langmuir isotherm fitting. Desorption and reusability experiments showed that MB
adsorption onto tea waste could be stable and could not cause secondary
pollution. The interaction mechanism between tea waste and MB involved
electrostatic attraction, hydrogen bond, ion exchange, π-π binding. The
organic functional groups of tea waste played an important role during the MB
removal process. Therefore, tea waste has the potential to act as an adsorbent to
remove MB from aqueous solution.
PMID- 29937525
TI - Endogenous Antiangiogenic Factors in Chronic Kidney Disease: Potential Biomarkers
of Progression.
AB - Chronic kidney disease (CKD) is a major global health problem. Unless intensive
intervention is initiated, some patients can rapidly progress to end-stage kidney
disease. However, it is often difficult to predict renal outcomes using
conventional laboratory tests in individuals with CKD. Therefore, many
researchers have been searching for novel biomarkers to predict the progression
of CKD. Angiogenesis is involved in physiological and pathological processes in
the kidney and is regulated by the balance between a proangiogenic factor,
vascular endothelial growth factor (VEGF)-A, and various endogenous
antiangiogenic factors. In recent reports using genetically engineered mice, the
roles of these antiangiogenic factors in the pathogenesis of kidney disease have
become increasingly clear. In addition, recent clinical studies have demonstrated
associations between circulating levels of antiangiogenic factors and renal
dysfunction in CKD patients. In this review, we summarize recent advances in the
study of representative endogenous antiangiogenic factors, including soluble fms
related tyrosine kinase 1, soluble endoglin, pigment epithelium-derived factor,
VEGF-A165b, endostatin, and vasohibin-1, in associations with kidney diseases and
discuss their predictive potentials as biomarkers of progression of CKD.
PMID- 29937529
TI - Investigation of the Influence of Pre-Charged Hydrogen on Fracture Toughness of
As-Received 2.25Cr1Mo0.25V Steel and Weld.
AB - Fracture failure caused by hydrogen embrittlement (HE) is a major concern for the
system reliability and safety of hydrogen storage vessels, which are generally
made of 2.25Cr1Mo0.25V steel. Thus, study of the influence of pre-charged
hydrogen on fracture toughness of as-received 2.25Cr1Mo0.25V steel and weld is of
significant importance. In the current work, the influence of hydrogen on
fracture toughness of as-received 2.25Cr1Mo0.25V steel and weld was
systematically studied. Base metal (BM) and weld metal (WM) specimens under both
hydrogen-free and hydrogen-charged conditions were tested using three-point
bending tests. Hydrogen was pre-charged inside specimens by the immersion
charging method. The J-integral values were calculated for quantitatively
evaluating the fracture toughness. In order to investigate the HE mechanisms,
optical microscopy (OM) and scanning electron microscopy (SEM) were used to
characterize the microstructure of BM and WM specimens. The results revealed that
the presence of pre-charged hydrogen caused a significant decrease of the
fracture toughness for both BM and WM specimens. Moreover, the pre-charged
hydrogen led to a remarkable transition of fracture mode from ductile to brittle
pattern in 2.25Cr1Mo0.25V steel.
PMID- 29937530
TI - Boron Nitride Nanosheets/PNIPAM Hydrogels with Improved Thermo-Responsive
Performance.
AB - Thermo-responsive hydrogel is an important smart material. However, its slow
thermal response rate limits the scope of its applications. Boron nitride
nanosheet-reinforced thermos-responsive hydrogels, which can be controlled by
heating, were fabricated by in situ polymerization of N-isopropylacrylamide in
the presence of boron nitride nanosheets. The hydrogels exhibit excellent thermo
responsiveness and much enhanced thermal response rate than that of pure poly(N
isopropylacrylamide) hydrogels. Interestingly, the hydrogels can be driven to
move in aqueous solution by heating. Importantly, the composite hydrogel is
hydrophilic at a temperature below lower critical solution temperature (LCST),
while it is hydrophobic at a temperature above LCST. Therefore, it can be used
for quick absorption and release of dyes and oils from water. All these
properties demonstrate the potential of hydrogel composites for water
purification and treatment.
PMID- 29937531
TI - Four Major South Korea's Rivers Using Deep Learning Models.
AB - Harmful algal blooms are an annual phenomenon that cause environmental damage,
economic losses, and disease outbreaks. A fundamental solution to this problem is
still lacking, thus, the best option for counteracting the effects of algal
blooms is to improve advance warnings (predictions). However, existing physical
prediction models have difficulties setting a clear coefficient indicating the
relationship between each factor when predicting algal blooms, and many variable
data sources are required for the analysis. These limitations are accompanied by
high time and economic costs. Meanwhile, artificial intelligence and deep
learning methods have become increasingly common in scientific research; attempts
to apply the long short-term memory (LSTM) model to environmental research
problems are increasing because the LSTM model exhibits good performance for time
series data prediction. However, few studies have applied deep learning models or
LSTM to algal bloom prediction, especially in South Korea, where algal blooms
occur annually. Therefore, we employed the LSTM model for algal bloom prediction
in four major rivers of South Korea. We conducted short-term (one week)
predictions by employing regression analysis and deep learning techniques on a
newly constructed water quality and quantity dataset drawn from 16 dammed pools
on the rivers. Three deep learning models (multilayer perceptron, MLP; recurrent
neural network, RNN; and long short-term memory, LSTM) were used to predict
chlorophyll-a, a recognized proxy for algal activity. The results were compared
to those from OLS (ordinary least square) regression analysis and actual data
based on the root mean square error (RSME). The LSTM model showed the highest
prediction rate for harmful algal blooms and all deep learning models out
performed the OLS regression analysis. Our results reveal the potential for
predicting algal blooms using LSTM and deep learning.
PMID- 29937532
TI - Development and Evaluation of Surfactant Nanocapsules for Chemical Enhanced Oil
Recovery (EOR) Applications.
AB - The primary objective of this study is the synthesis of nanocapsules (NC) that
allow the reduction of the adsorption process of surfactant over the porous media
in enhanced oil recovery processes. Nanocapsules were synthesized through the
nanoprecipitation method by encapsulating commercial surfactants Span 20 and
Petro 50, and using type II resins isolated from vacuum residue as a shell. The
NC were characterized using dynamic light scattering, transmission electron
microscopy, Fourier transform infrared, solvency tests, softening point
measurements and entrapment efficiency. The obtained NC showed spherical geometry
with sizes of 71 and 120 nm for encapsulated Span 20 (NCS20), and Petro 50
surfactant (NCP50), respectively. Also, the NCS20 is composed of 90% of
surfactant and 10% of type II resins, while the NCP50 material is 94% of
surfactant and 6% of the shell. Nanofluids of nanocapsules dispersed in deionized
water were prepared for evaluating the nanofluid—sandstone interaction from
adsorption phenomena using a batch-mode method, contact angle measurements, and
FTIR analysis. The results showed that NC adsorption was null at the different
conditions of temperatures evaluated of 25, 50, and 70 °C, and stirring
velocities up to 10,000 rpm. IFT measurements showed a reduction from 18 to 1.62
and 0.15 mN/m for the nanofluids with 10 mg/L of NCS20, and NCP50 materials,
respectively. Displacements tests were conducted using a 20 °API crude oil in
a quarter five-spot pattern micromodel and showed an additional oil recovery of
23% in comparison with that of waterflooding, with fewer pore volumes injected
than when using a dissolved surfactant.
PMID- 29937533
TI - Prevalence, Severity and Potential Nutritional Causes of Gastrointestinal
Symptoms during a Marathon in Recreational Runners.
AB - The purpose of the present study was to investigate the prevalence of
gastrointestinal symptoms (GIS) amongst recreational runners during a marathon
race, and potential nutritional factors that may contribute. Recreational runners
of the 2017 Liverpool (n = 66) and Dublin (n = 30) marathons were recruited. GIS
were reported post-marathon and we considered GIS in the 7 days prior to the
marathon and during the marathon using the Gastrointestinal Symptom Rating Scale
(GSRS). Nutritional intake was recorded using food diaries for the day before the
race, morning of the race, and during the race; 43% of participants reported
moderate (≥4) GIS in the 7 days prior to the marathon and 27% reported
moderate symptoms during the marathon with most common symptoms being flatulence
(16%) during training, and nausea (8%) during the marathon race. Correlations
between all nutritional intake and GIS were not statistically significant (p >
0.05). There were significant correlations between total GIS score (r = 0.510, p
< 0.001), upper GIS score (r = 0.346, p = 0.001) and lower GIS score (r = 0.483,
p < 0.001) in training and during the marathon. There appears to be a modest
prevalence of GIS in recreational runners, in the week prior to a marathon and
during marathon running, although there was no association with nutritional
intake before or during the race.
PMID- 29937534
TI - Mechanical Structural Design of a Piezoresistive Pressure Sensor for Low-Pressure
Measurement: A Computational Analysis by Increases in the Sensor Sensitivity.
AB - This paper proposes a novel micro-electromechanical system (MEMS) piezoresistive
pressure sensor with a four-petal membrane combined with narrow beams and a
center boss (PMNBCB) for low-pressure measurements. The stresses induced in the
piezoresistors and deflection of the membrane were calculated using the finite
element method (FEM). The functions of the relationship between the dimension
variables and mechanical performance were determined based on the curve fitting
method, which can provide an approach for geometry optimization of the sensor. In
addition, the values in the equations were varied to determine the optimal
dimensions for the proposed membrane. Then, to further improve the sensitivity of
the sensor, a series of rectangular grooves was created at the position of the
piezoresistors. The proposed diaphragm was compared to existing diaphragms, and a
considerable increase in the sensitivity and a considerable decrease in
nonlinearity error could be achieved by using the proposed sensor. The simulation
results suggest that the sensor with the PMNBCB structure obtained a high
sensitivity of 34.67 mV/kPa and a low nonlinearity error of 0.23% full-scale span
(FSS) for the pressure range of 0-5 kPa. The proposed sensor structure is a
suitable selection for MEMS piezoresistive pressure sensors.
PMID- 29937535
TI - Social Risk Factors of Transportation PPP Projects in China: A Sustainable
Development Perspective.
AB - Public-private partnerships (PPPs) have become increasingly important in
improving the sustainability of society in China, with transportation being the
largest investment area. However, the Social Risk Factors (SRFs) of
transportation PPPs in China, which serve as a useful tool for distinguishing
strengths and weaknesses for effective social risk management (SRM), have not
been clearly identified. A conceptual model including 3 risk dimensions and 15
SRFs was proposed to mitigate social risks and improve the social sustainability
of transportation PPP projects. A questionnaire survey conducted to investigate
stakeholders’ opinions on the proposed SRFs demonstrated that all the SRFs
were important. The SRFs can be used to evaluate social risks from economic,
environmental, and social dimensions. Confirmatory factor analysis (CFA) verified
the classification of the SRFs and indicated that all the risk dimensions
contributed to social risks. The social and environmental impacts on social
sustainability may contribute more to the generation of social risks.
Furthermore, the concept of people-first PPPs was proposed to reduce social risks
from the perspective of different stakeholders, with the interactions among
different stakeholders being prioritized. The identified SRFs and their
relationships can improve our understanding of SRM in the delivery of social
sustainability and improve social resilience.
PMID- 29937536
TI - Allicin Bioavailability and Bioequivalence from Garlic Supplements and Garlic
Foods.
AB - Allicin is considered responsible for most of the pharmacological activity of
crushed raw garlic cloves. However, when garlic supplements and garlic foods are
consumed, allicin bioavailability or bioequivalence (ABB) has been unknown and in
question because allicin formation from alliin and garlic alliinase usually
occurs after consumption, under enzyme-inhibiting gastrointestinal conditions.
The ABB from 13 garlic supplements and 9 garlic foods was determined by bioassay
for 13 subjects by comparing the area under the 32-h concentration curve of
breath allyl methyl sulfide (AMS), the main breath metabolite of allicin, to the
area found after consuming a control (100% ABB) of known allicin content:
homogenized raw garlic. For enteric tablets, ABB varied from 36-104%, but it was
reduced to 22-57% when consumed with a high-protein meal, due to slower gastric
emptying. Independent of meal type, non-enteric tablets gave high ABB (80-111%),
while garlic powder capsules gave 26-109%. Kwai garlic powder tablets, which have
been used in a large number of clinical trials, gave 80% ABB, validating it as
representing raw garlic in those trials. ABB did not vary with alliinase
activity, indicating that only a minimum level of activity is required. Enteric
tablets (high-protein meal) disintegrated slower in women than men. The ABB of
supplements was compared to that predicted in vitro by the dissolution test in
the United States Pharmacopeia (USP); only partial agreement was found. Cooked or
acidified garlic foods, which have no alliinase activity, gave higher ABB than
expected: boiled (16%), roasted (30%), pickled (19%), and acid-minced (66%).
Black garlic gave 5%. The mechanism for the higher than expected ABB for
alliinase-inhibited garlic was explored; the results for an alliin-free/allicin
free extract indicate a partial role for the enhanced metabolism of γ
glutamyl S-allylcysteine and S-allylcysteine to AMS. In conclusion, these largely
unexpected results (lower ABB for enteric tablets and higher ABB for all other
products) provide guidelines for the qualities of garlic products to be used in
future clinical trials and new standards for manufacturers of garlic powder
supplements. They also give the consumer an awareness of how garlic foods might
compare to the garlic powder supplements used to establish any allicin-related
health benefit of garlic.
PMID- 29937537
TI - Trends in Lung Cancer Incidence in Delhi, India 1988-2012: Age-Period-Cohort and
Joinpoint Analyses
AB - Introduction: Lung cancer (LC) has been one of the most commonly diagnosed
cancers worldwide, both in termsof new cases and mortality. Exponential growth of
economic and industrial activities in recent decades in the Delhiurban area may
have increased the incidence of LC. The primary objective of this study was to
evaluate the time trendaccording to gender. Method: LC incidence data over 25
years were obtained from the population based urban Delhicancer registry.
Joinpoint regression analysis was applied for evaluating the time trend of age
standardized incidencerates. The age-period-cohort (APC) model was employed using
Poisson distribution with a log link function and theintrinsic estimator method.
Results: During the 25 years, 13,489 male and 3,259 female LC cases were
registered,accounting for 9.78% of male and 2.53% of female total cancer cases.
Joinpoint regression analysis revealed that LCincidence in males continued to
increase during the entire period, a sharp acceleration being observed starting
from2009. In females the LC incidence rate remained a plateau during 1988-2002
and thereafter increased. The cumulativerisks for 1988-2012 were 1.79% and 0.45%.
The full APC (IE) model showed best fit for an age-period-cohort effecton LC
incidence, with significant increase with age peaking at 70-74 years in males and
65-69 years in females. Arising period effect was observed after adjusting for
age and cohort effects in both genders and a declining cohort effectwas
identified after controlling for age and period effects. Conclusion: The
incidence of LC in urban Delhi showedincreasing trend from 1988-2012. Known
factors such as environmental conservation, tobacco control, physical
activityawareness and medical security should be implemented more vigorously over
the long term in our population.
PMID- 29937538
TI - Pulmonary Fat Embolism and Coronary Amyloidosis.
AB - BACKGROUND Fat embolism syndrome is a well-known complication in orthopedic and
trauma surgery, caused by a massive release of fat into the circulation that can
lead to cardiopulmonary insufficiency and multiorgan failure. CASE REPORT We
present the case of a 72-year-old man with osteoarthritis who underwent an
elective right cementless total hip arthroplasty. Two hours after surgery, the
patient lost consciousness and was found hypotensive and with reduced oxygen
saturation, with a severe right heart dilatation at echocardiographic evaluation.
Death occurred after cardiopulmonary resuscitation attempts. Post-mortem
microscopic examination revealed that the final cause of death was pulmonary fat
embolism associated with coronary amyloidosis and atherosclerosis. CONCLUSIONS
This case called our attention on the sudden onset of fat embolism syndrome after
arthroplasty and the insidious nature of amyloidosis infiltrative disease. The
autopsy findings substantially aided understanding the immediate cause of death.
PMID- 29937540
TI - Culturing the human microbiota and culturomics.
AB - The gut microbiota has an important role in the maintenance of human health and
in disease pathogenesis. This importance was realized through the advent of omics
technologies and their application to improve our knowledge of the gut microbial
ecosystem. In particular, the use of metagenomics has revealed the diversity of
the gut microbiota, but it has also highlighted that the majority of bacteria in
the gut remain uncultured. Culturomics was developed to culture and identify
unknown bacteria that inhabit the human gut as a part of the rebirth of culture
techniques in microbiology. Consisting of multiple culture conditions combined
with the rapid identification of bacteria, the culturomic approach has enabled
the culture of hundreds of new microorganisms that are associated with humans,
providing exciting new perspectives on host-bacteria relationships. In this
Review, we discuss why and how culturomics was developed. We describe how
culturomics has extended our understanding of bacterial diversity and then
explore how culturomics can be applied to the study of the human microbiota and
the potential implications for human health.
PMID- 29937539
TI - Association Between Changes in Splanchnic Hemodynamics and Risk Factors of Portal
Venous System Thrombosis After Splenectomy with Periesophagogastric
Devascularization.
AB - BACKGROUND The purpose of this study was to investigate splanchnic hemodynamic
changes and determine an optimal cutoff value for risk factors of portal venous
system thrombosis (PVST) after splenectomy with periesophagogastric
devascularization (SPD) in cirrhotic patients with esophageal and gastric
variceal bleeding (EGVB) and portal hypertension (PH). MATERIAL AND METHODS Data
on patients who underwent SPD were collected retrospectively from January 2013 to
December 2017. Color Doppler ultrasound was performed to detect hemodynamic
changes of the hepatic artery, splenic artery, splenic vein, and portal vein in
included patients (n=60) and healthy volunteers (n=30). Outcomes were compared
between preoperative and postoperative biochemical indicators. The cutoff values
for hemodynamics were identified using receiver operating characteristic (ROC)
curve analysis, and univariate and multivariate analyses of risk factors of PVST
were performed. RESULTS In our series, hemodynamic indexes of splenic artery,
spleen vein, and portal vein in the study group were significantly higher than
that of the control group (P<0.05). Multivariate analysis revealed that the
portal vein flow and the internal diameter of the portal vein were significantly
correlated with PVST. The ROC analysis revealed that the cutoff points for portal
vein flow and internal diameter of the splenic vein and portal vein were
>=1822.32 ml/min, >=1.37 cm, and >=1.56 cm, respectively. CONCLUSIONS SPD is an
effective treatment in cirrhotic patients with concomitant EGVB and PH by
increasing hepatic artery flow and decreasing portal vein flow. High portal vein
flow and wider diameters of the portal vein and splenic vein are important
markers of PVST.
PMID- 29937541
TI - Autologous Skin-Grafting Surgery for the Prevention of Esophageal Stenosis After
Complete Circular Endoscopic Submucosal Tunnel Dissection.
PMID- 29937542
TI - Non-Invasive Diagnosis of Nonalcoholic Fatty Liver Disease.
PMID- 29937543
TI - Ovarian stimulation for IVF and risk of primary breast cancer in BRCA1/2 mutation
carriers.
AB - BACKGROUND: The effect of in vitro fertilisation (IVF) on breast cancer risk for
BRCA1/2 mutation carriers is rarely examined. As carriers may increasingly
undergo IVF as part of preimplantation genetic diagnosis (PGD), we examined the
impact of ovarian stimulation for IVF on breast cancer risk in BRCA1/2 mutation
carriers. METHODS: The study population consisted of 1550 BRCA1 and 964 BRCA2
mutation carriers, derived from the nationwide HEBON study and the nationwide PGD
registry. Questionnaires, clinical records and linkages with the Netherlands
Cancer Registry were used to collect data on IVF exposure, risk-reducing
surgeries and cancer diagnosis, respectively. Time-dependent Cox regression
analyses were conducted, stratified for birth cohort and adjusted for
subfertility. RESULTS: Of the 2514 BRCA1/2 mutation carriers, 3% (n = 76) were
exposed to ovarian stimulation for IVF. In total, 938 BRCA1/2 mutation carriers
(37.3%) were diagnosed with breast cancer. IVF exposure was not associated with
risk of breast cancer (HR: 0.79, 95% CI: 0.46-1.36). Similar results were found
for the subgroups of subfertile women (n = 232; HR: 0.73, 95% CI: 0.39-1.37) and
BRCA1 mutation carriers (HR: 1.12, 95% CI: 0.60-2.09). In addition, age at and
recency of first IVF treatment were not associated with breast cancer risk.
CONCLUSION: No evidence was found for an association between ovarian stimulation
for IVF and breast cancer risk in BRCA1/2 mutation carriers.
PMID- 29937545
TI - On the mechanisms of secondary flows in a gas vortex unit.
AB - The hydrodynamics of secondary flow phenomena in a disc-shaped gas vortex unit
(GVU) is investigated using experimentally validated numerical simulations. The
simulation using ANSYS FLUENT(r) v.14a reveals the development of a backflow
region along the core of the central gas exhaust, and of a counterflow
multivortex region in the bulk of the disc part of the unit. Under the tested
conditions, the GVU flow is found to be highly spiraling in nature. Secondary
flow phenomena develop as swirl becomes stronger. The backflow region develops
first via the swirl-decay mechanism in the exhaust line. Near-wall jet formation
in the boundary layers near the GVU end-walls eventually results in flow reversal
in the bulk of the unit. When the jets grow stronger the counterflow becomes
multivortex. The simulation results are validated with experimental data obtained
from Stereoscopic Particle Image Velocimetry and surface oil visualization
measurements.
PMID- 29937544
TI - Interaction of WBP2 with ERalpha increases doxorubicin resistance of breast
cancer cells by modulating MDR1 transcription.
AB - BACKGROUND: Surgery combined with new adjuvant chemotherapy is the primary
treatment for early stage invasive and advanced stage breast cancer. Growing
evidence indicates that patients with ERalpha-positive breast cancer show poor
response to chemotherapeutics. However, ERalpha-mediated drug-resistant
mechanisms remain unclear. METHODS: Levels of WW domain-binding protein 2 (WBP2)
and drug-resistant gene were determined by western blotting and RT-PCR,
respectively. Cell viability was measured by preforming MTT assay. CD243
expression and apoptosis rate were evaluated by flow cytometry. Interactions of
WBP2/ERalpha and ERalpha/MDR1 were detected by co-immunoprecipitation and
chromatin immunoprecipitation (ChIP) assay, respectively. RESULTS: There was an
intrinsic link between WBP2 and ERalpha in drug-resistant cancer cells.
Upregulation of WBP2 in MCF7 cells increased the chemoresistance to doxorubicin,
while RNAi-mediated knockdown of WBP2 in MCF7/ADR cells sensitised the cancer
cells to doxorubicin. Further investigation in in vitro and in vivo models
demonstrated that WBP2 expression was directly correlated with MDR1, and WBP2
could directly modulate MDR1 transcription through binding to ERalpha, resulting
in increased chemotherapy drug resistance. CONCLUSIONS: Our finding provides a
new mechanism for the chemotherapy response of ERalpha-positive breast tumours,
and WBP2 might be a key molecule for developing new therapeutic strategies to
treat chemoresistance in breast cancer patients.
PMID- 29937546
TI - Approaches to Identifying the Emerging Innovative Water Technology Industry in
the United States.
AB - Clean water is vital to sustaining our natural environment, human health, and our
economy. As infrastructure continues to deteriorate and water resources become
increasingly threatened, new technologies will be needed to ensure safe and
sustainable water in the future. Though the US water industry accounts for
approximately 1% gross domestic product and regional "clusters" for water
technology exist throughout the country, this emerging industry has not been
captured by recent studies. As use of the term "cluster" becomes more prevalent,
regional mapping efforts have revealed international differences in definition
yet showcase this industry's economic impact. In reality, institutional processes
may inhibit altering industry coding to better describe water technology.
Forgoing the benefits of national economic tracking, alternative data sets are
available, which may support new ways of identifying these clusters. This work
provides cluster definitions; summarizes current approaches to identifying
industry activity using data, interviews, and literature; and sets a foundation
for future research.
PMID- 29937547
TI - Strain-induced modulation of near-field radiative transfer.
AB - In this theoretical study, we present a near-field thermal modulator that
exhibits change in radiative heat transfer when subjected to mechanical
stress/strain. The device has two terminals at different temperatures separated
by vacuum: one fixed and one stretchable. The stretchable side contains one
dimensional grating. When subjected to mechanical strain, the effective optical
properties of the stretchable side are affected upon deformation of the grating.
This results in modulation of surface waves across the interfaces influencing
near-field radiative heat transfer. We show that for a separation of 100 nm, it
is possible to achieve 25% change in radiative heat transfer for a strain of 10%.
PMID- 29937548
TI - The body-space relations of research(ed) on bodies: The experiences of becoming
participant researchers.
AB - This paper heeds calls for reflections on how the research field is defined
through embodied socio-spatial presence and immediacy. Focusing on classroom
"body-training" observations that were part of a larger qualitative research
project, and on the field notes and reflections of three researchers, we explore
the transition from observer-researchers to participant-researchers. That is, we
explore how, by researching others, we unexpectedly became researched on as our
own bodies became instruments in the research process and were used to elicit
knowledge on embodied learning, body-mapping and corporeal trace. As a
methodological intervention, conducting research through the body, the
positioning of bodies and body-to-body interaction, can tell us much about the
often ignored embodied and emotional dimensions of the research field. But, in
addition, it can elucidate the power relations between, and the fluidity of,
researcher and researched positions in the jolting of secured researcher
identity. Here we detail how different researchers performed different embodied
and emotional subjectivities in different training research spaces. We explore
how ontological anxieties of our own placed bodies, based around constructed
notions of femininity, religion and researcher professionalism, shape this
immediate body-to-body encounter and the subsequent research process.
PMID- 29937549
TI - Second Epoch VLBA Calibrator Survey Observations - VCS-II.
AB - Six very successful VLBA calibrator survey campaigns were run between 1994 and
2007 to build up a large list of compact radio sources with positions precise
enough for use as VLBI phase reference calibrators. We report on the results of a
second epoch VLBA Calibrator Survey campaign (VCS-II) in which 2400 VCS sources
were re-observed at X and S bands in order to improve the upcoming third
realization of the International Celestial Reference Frame (ICRF3) as well as to
improve their usefulness as VLBI phase reference calibrators. In this survey,
some 2062 previously detected sources and 324 previously undetected sources were
detected and revised positions are presented. Average position uncertainties for
the re-observed sources were reduced from 1.14 and 1.98 mas to 0.24 and 0.41 mas
in RA and Declination, respectively, or by nearly a factor of 5. Minimum detected
flux values were approximately 15 and 28 mJy in X and S bands, respectively, and
median total fluxes are approximately 230 and 280 mJy. The vast majority of these
sources are flat-spectrum sources, with ~82% having spectral indices greater than
-0.5.
PMID- 29937550
TI - Structural changes in the S3 state of the oxygen evolving complex in photosystem
II.
AB - The S3 state of the Mn4 CaO5 -cluster in photosystem II was investigated by DFT
calculations and compared with EXAFS data. Considering previously proposed
mechanism; a water molecule is inserted into an open coordination site of Mn upon
S2 to S3 transition that becomes a substrate water, we examined if the water
insertion is essential for the S3 formation, or if one cannot eliminate other
possible routes that do not require a water insertion at the S3 stage. The novel
S3 state structure consisting of only short 2.7-2.8 A Mn-Mn distances was
discussed.
PMID- 29937551
TI - Sanitation, Disease Externalities and Anaemia: Evidence From Nepal.
AB - Anaemia impairs physical and cognitive development in children and reduces human
capital accumulation. The prior economics literature has focused on the role of
inadequate nutrition in causing anaemia. This article is the first to show that
sanitation, a public good, significantly contributes to preventing anaemia. We
identify effects by exploiting rapid and differential improvement in sanitation
across regions of Nepal between 2006 and 2011. Within regions over time, cohorts
of children exposed to better community sanitation developed higher haemoglobin
levels. Our results highlight a previously undocumented externality of open
defaecation, which is today practiced by over a billion people worldwide.
PMID- 29937552
TI - The determinants of Italian NEETs and the effects of the economic crisis.
AB - In recent years, the share of young people not in education, employment, or
training (NEETs) has shown a remarkable increase in many European countries, such
as Italy. The wide diffusion of NEETs represents an alarming social issue, as
being NEET predisposes young people to long-term unemployment and social
exclusion. It also has a significant negative impact on the economic growth and
welfare equilibrium of countries. The aim of this paper is to analyze the
determinants of the NEET condition in Italy through a step by step procedure
beginning with the identification of their main characteristics and then
proceeding with a focus on specific homogeneous clusters of NEETs. The
decomposition of the gaps in the probabilities of being NEET between the various
clusters allows verifying how personal characteristics effectively act.
Furthermore, the influence of unobserved factors in the professional condition of
young people has been analysed in more detail through a bivariate selection
probit model on the propensity to look for a job against the condition of being
inactive. The results confirm the crucial role of the education system, as well
as the importance of the economic and social disparities between gender and the
Italian territorial districts.
PMID- 29937553
TI - Does the Type of Higher Education Affect Labor Market Outcomes? Evidence from
Egypt and Jordan.
AB - In Egypt and Jordan there is a substantial mismatch between the output of the
higher education system and the needs of the labor market. Both demand and supply
side factors could be driving this mismatch. This paper tests a key supply-side
issue, whether differences in the institutional structures and incentives in
higher education affect the labor market outcomes of graduates. Specifically, we
ask if the stronger alignment of incentives in private relative to public higher
education institutions produces more employable human capital and better labor
market outcomes. We examine the impact of the type of higher education
institution a person attends on several labor market outcomes while controlling
for his or her pre-enrollment characteristics. The results demonstrate that
supply-side issues and institutional incentives have little impact on labor
market outcomes while family background plays by far the largest role. Proposed
reforms for higher education often suggest increasing the role of the private
sector in provision of higher education. Our findings indicate that this approach
is unlikely to improve labor market outcomes.
PMID- 29937554
TI - Association between Psoriasis and Helicobacter pylori Infection: A Systematic
Review and Meta-analysis.
AB - Background/Purpose: Helicobacter pylori infection has been suggested as a culprit
of various extragastrointestinal (GI) disorders. It is debatable whether H.
pylori infection exacerbates or triggers the pathogenesis of psoriasis. This meta
analysis aimed to explore the association between psoriasis and H. pylori
infection. Materials and Methods: A comprehensive search of the MEDLINE and
EMBASE databases was performed from inception through October 2017. The inclusion
criterion was observational studies evaluating the association between psoriasis
and H. pylori infection. The pooled odds ratio (OR) of H. pylori infection and
their 95% confidence interval (CI) were calculated using a random-effects meta
analysis to compare risk between psoriasis patients and controls. The between
study heterogeneity of effect-size was quantified using the Q statistic and I2.
Results: Data were extracted from nine observational studies involving 1546
individuals. Pooled result demonstrated an increased H. pylori infection in
psoriasis compared with controls (OR=1.58; 95% CI: 1.02-2.46, P =0.04, I2=64%).
Subgroup analysis showed an increased risk of H. pylori infection in psoriasis
measured with H. pylori IgG enzyme-linked immunosorbent assay (OR=3.11; 95% CI:
1.85-5.20, P <0.01, I2=10%) but not active infection measured with urea breath
test (OR=0.88; 95% CI: 0.61-1.27, P =0.49, I2=0%). Conclusion: This meta-analysis
has shown an increased H. pylori infection in patients with psoriasis. H. pylori
infection in the past could play a role in the abnormal immunological cascade in
the pathogenesis of psoriasis. Further studies to elucidate the inflammatory
response in the pathogenesis of psoriasis are warranted.
PMID- 29937555
TI - The Effect of Candida albicans on the Expression Levels of Toll-like Receptor 2
and Interleukin-8 in HaCaT Cells Under High- and Low-glucose Conditions.
AB - Background: The diabetics are prone to skin infections, especially with Candida
albicans. It is important to elucidate the different antifungal abilities of
patients with hyperglycemia and healthy controls for the treatment of this
condition. The toll-like receptor 2 (TLR2) and interleukin (IL)-8 secreted by
keratinocytes counteract C. albicans. Aim: This study aims to explore the
differential expression of toll-like receptor 2 (TLR2) and interleukin (IL)-8
secretion by keratinocytes between controls and diabetic patients when challenged
with C. albicans. Materials and Methods: HaCaT cells were cultured in high
glucose (HG) Dulbecco's modified Eagle's medium (DMEM) and low-glucose (LG) DMEM.
Then, they were exposed to C. albicans hyphae for 24 h. The expression levels of
TLR2 and IL-8 were determined at different periods in both the HG and LG groups.
Real-time polymerase chain reaction analysis, western blotting, and enzyme-linked
immunosorbent assays were performed in this study. The morphological changes of
HaCaT cells under two different glucose concentrations were also observed.
Results: We found that the expression levels of both TLR2 and IL-8 increased and
then decreased in the two groups. Notably, the IL-8 levels in the LG group were
higher than those in the HG group at each time point (P <0.05), and the TLR2
levels in the LG group were higher than those in the HG group at the beginning of
the experiment and after 24 h of treatment with C. albicans (P <0.05). In each
group, the levels of IL-8 and TLR2 at the secretion peak were significantly
different from those in the initial and the last period of observation (P <0.05).
The cellular morphology of HaCaT cells treated with different concentrations of
glucose was also similar. However, with prolonged coculture time, cell death
increased. Conclusion: These observations showed that TLR2 and IL-8 act on the
keratinocytes interacting with C. albicans, and HG status might affect the
function of HaCaT cells by reducing the secretion of IL-8 and TLR2.
PMID- 29937557
TI - Study of S100 Immunostaining in Demonstrating Neural Granulomas in Paucibacillary
Leprosy.
AB - Context: Neural granulomas are hallmark of leprosy. Challenges faced in
diagnosing paucibacillary leprosy include: (i) Difficult visualization of nerve
twigs on hematoxylin and eosin (H and E) sections due to their small size and
(ii) Paucity of organisms on acid-fast bacilli stain. Aims: (1) This study aimed
to test the role of S100 immunostain in demonstrating neural granulomas in skin
biopsies of paucibacillary leprosy, (2) to compare morphology of S100 staining of
nerves inside granulomas among clinicohistologically defined different types of
leprosy, and (3) to test whether the pattern of S100 immunostaining can
distinguish nerve fragmentation/destruction from a normal intact nerve in skin
biopsy. Materials and Methods: Sixty four diagnosed cases of leprosy were
included in this study. Five skin biopsies with no significant pathology (for
studying intact nerve) and nine nonleprosy cutaneous granulomas were also
studied. Results: (i) In demonstrating neural granuloma, sensitivity of H and E
was 48.27% and that of S100 was 100%, (ii) Morphology of nerve fragments on S100
stain for cases of leprosy was fragmented and infiltrated in 37, intact and
infiltrated in 19, reduced, fragmented, and infiltrated in seven, and absent in
one, (iii) There was a significant difference (P <0.001) in the pattern of
staining of S100 on intact nerve and nerves involved by granuloma in leprosy, and
(iv) The probability to differentiate between leprosy and nonleprosy granuloma
was statistically significant (P <0.001). Conclusion: S100 immunostaining showed
to be an effective adjuvant to histopathology in diagnosing paucibacillary
leprosy and differentiating it from nonleprosy cutaneous granuloma.
PMID- 29937556
TI - The Role of Forkhead Box Class O3A and SIRT1 Gene Variants in Early-Onset
Psoriasis.
AB - Background: Psoriasis is a chronic inflammatory skin disorder, which is
characterized by a heightened immunological response. Although the immunogenetics
of this chronic inflammatory disorder is poorly understood, its expression is
known to be dependent on proinflammatory cytokines. It is known that two distinct
subtypes of chronic plaque psoriasis: Early-onset psoriasis (EOP) before the age
of 40 years and late-onset psoriasis after the age of 40 years. Forkhead box
class O3A (FOXO3A) is a transcription factor, which plays an important role in
cell-cycle regulation, apoptosis, oxidative stress, and DNA repair. The silent
information regulator (SIRT) is thought to have a role in skin disorders,
including psoriasis, that are characterized by hyperproliferation and
inflammation. Aim: The aim of this study was to investigate FOXO3A and SIRT1 gene
polymorphisms in EOP. Methods: The study group consisted of 142 EOP patients and
123 unrelated healthy controls. FOXO3A polymorphisms were determined using the
polymerase chain reaction (PCR)-restriction fragment length polymorphism method.
SIRT1 gene polymorphisms were determined by PCR-confronting two-pair primers
methods. Results: The FOXO3A rs4946936 and SIRT1 rs7069102 gene polymorphisms
were positively correlated with EOP and disease severity. The GG genotype
frequency of SIRT1 rs7069102 gene polymorphisms was increased in severe EOP. The
CC frequency of FOXO3A rs4946936 was increased in EOP with nail disorders.
Conclusion: The rs7069102 gene polymorphism of SIRT1 and rs4946936 polymorphism
of FOXO3A are associated with early onset psoriasis; this may be responsible for
increased keratinocyte proliferation in the pathogenesis of psoriasis and disease
severity.
PMID- 29937558
TI - Polymorphism of FAS and FAS Ligand Genes in Alopecia Areata: A Case-control Study
in Egyptian Population.
AB - Background: Alopecia areata (AA) is a common dermatologic disease with suspected
autoimmune etiology. Tumor necrosis factor superfamily member 6 or CD95 (FAS) and
FAS ligand (FASL) are proapoptotic proteins. The relationship between apoptosis
and autoimmunity is well recognized. Inflammatory T cells in AA are cytotoxic and
possess FAS/FASL antigens. Aim: This study aims to investigate the association
between FAS-670 A/G and FASL-124 A/G gene polymorphisms and AA to clarify if
these polymorphisms influence disease occurrence or increase disease risk.
Materials and Methods: A case-control study was conducted on sixty patients with
AA, and 40 age- and sex-matched healthy subjects, as a control group. Disease
severity was assessed by severity of alopecia tool (SALT) Score. FAS 670A/G and
FASL 124A/G gene polymorphisms were investigated by the restriction fragment
length polymorphism polymerase chain reaction. Results: For FAS gene, G/G
genotype was significantly higher in cases than in control group with odds ratio
5.1. G allele was more prevalent among patient group with odds ratio 1.75. For
FASL gene, A/G genotype was significantly higher in cases than in control group
with odds ratio 4.53. G allele was more prevalent among patient group with odds
ratio 1.88. GG genotype of FAS was significantly associated with longer disease
duration (P =0.001), recurrent attacks (P =0.01), higher SALT score (P =0.009),
alopecia universalis (P =0.002), and severe disease (P =0.006). Conclusion: FAS
and FASL gene polymorphisms are associated with AA. Further large-scale studies
on different ethnicities are required for more clarification of their role in
disease development. Therapeutic modalities based on their inhibition could be
promising in the treatment of a common disease like AA.
PMID- 29937559
TI - Serum Zinc Level in Vitiligo: A Case-control Study.
AB - Background: Vitiligo is characterized by the idiopathic destruction of
melanocytes, probably of autoimmune etiology, that results in depigmented patches
of skin and mucosal surfaces. Oxidative stress may contribute to the pathogenesis
of vitiligo. Zinc, a trace element with antiapoptotic properties, plays a major
role in the process of melanogenesis and elimination of free radicals. The
present study was conducted with the aim of comparing serum zinc levels in
patients with vitiligo and in normal controls. Materials and Methods: In this
case-control study, we studied 103 patients with vitiligo and 103 healthy sex-and
age-matched controls. Serum zinc levels were measured in these two groups using
atomic absorption spectrophotometry and compared with each other. Results: The
mean serum zinc level was 92.1 mcg/dl in the focal vitiligo, 81.3 mcg/dl in the
generalized vitiligo, and 91.8 mcg/dl in the control group. A significant
difference in serum zinc levels was observed between the patients with
generalized vitiligo and the controls. Lower serum zinc levels were also
correlated with longer duration of the disease. Furthermore, a negative
relationship was found between serum zinc level and age of patients with
vitiligo. Conclusion: Serum zinc level is low in patients with generalized
vitiligo. In these patients, serum zinc level is in negative correlation with
patient's age and disease duration.
PMID- 29937560
TI - Re-appraisal of Keratinocytes' Role in Vitiligo Pathogenesis.
AB - Background: Vitiligo is a common pigmentary disorder. Studies on its pathogenesis
extensively investigated melanocytes' abnormalities and few studies searched for
keratinocytes' role in disease development. Liver X receptor-alpha (LXR-alpha) is
a member of nuclear hormone receptors that acts as a transcription factor. Its
target genes are the main regulators of melanocyte functions. Aim: The aim of
this study is to investigate keratinocytes' role in vitiligo pathogenesis through
immunohistochemical expression of LXR-alpha in lesional, perilesional, and
distant nonlesional vitiligo skin. Materials and Methods: This case-control study
was carried out on 44 participants. These included 24 patients with vitiligo and
20 age- and sex-matched normal individuals as a control group. Biopsies, from
cases, were taken from lesional, perilesional, and distant nonlesional areas.
Evaluation was done using immunohistochemical technique. Results: Keratinocyte
LXR-alpha expression was upregulated in the lesional and perilesional skin
(follicular and interfollicular epidermis) compared with control skin (P <0.001
for all). There was significant association between higher histoscore (H-score)
in lesional epidermis (P <0.001) and in hair follicle (P =0.001) and the presence
of angiogenesis. There was significant association between higher H-score in
lesional epidermis and suprabasal vacuolization (P =0.02). No significant
association was found between H-score or expression percentage and clinical data
of selected cases. Conclusion: LXR-alpha upregulation is associated with
keratinocyte damage in vitiligo lesional skin that leads to decreased
keratinocyte-derived mediators and growth factors supporting the growth and/or
melanization of surrounding melanocytes. Therefore, melanocyte function and
survival are affected.
PMID- 29937561
TI - Do Prolactin and its Receptor Play a Role in Alopecia Areata?
AB - Context: Studying the link between prolactin and autoimmunity has gained much
ground over the past years. Its role played in alopecia areata (AA) is not clear
yet, as previous reports yielded controversial results. Aims: This study aimed to
measure the serum level of prolactin and to detect the expression of its receptor
in AA, in an attempt to highlight its possible role in the pathogenesis of this
disease. Subjects and Methods: A case-control study of 30 AA patients and 20
controls from outpatient clinic were undertaken. Every patient was subjected to
history taking and clinical examination to determine the severity of alopecia
tool (SALT) score. Blood samples were taken from patients and controls to
determine the serum prolactin level. Scalp biopsies were obtained from the
lesional skin of patients and normal skin of controls for assessment of the
prolactin receptor. Statistical Analysis: Depending upon the type of data, t
test, analysis of variance test, Chi-square, receiver operator characteristic
curve were undertaken. Results: On comparing the serum prolactin level between
patients and controls, no significant difference was found, while the mean tissue
level of prolactin receptor was significantly higher in patients than in
controls. In patients, a significant positive correlation was found between the
prolactin receptor and the SALT score. Conclusions: Prolactin plays a role in AA,
and this role is probably through the prolactin receptors rather than the serum
prolactin level.
PMID- 29937562
TI - Assessment of Heavy Metal and Trace Element Levels in Patients with Telogen
Effluvium.
AB - Background: Despite a multitude of studies, etiology of primary chronic telogen
effluvium (TE) remains incompletely understood. Essential heavy metals are
associated with beneficial effects in humans as well as in other living
organisms. However, they may lead to toxic effects when the exposure exceeds the
higher tolerable limits. We wanted to assess the heavy metal and trace element
levels in patients with chronic TE. Materials and Methods: A total of 40 subjects
with chronic TE were included in the study, and 30 healthy women served as
control. General and dermatological examinations were taken up in all
individuals. Those patients with positive hair pull test were evaluated with the
help of a trichogram. The presence of >20% telogen hair as documented by
trichogram was a requirement for the study inclusion. UNICAM-929
spectrophotometry device was used for determining serum trace element and heavy
metal concentrations. Results: In spite of an absence of significant differences
in terms of average Zn concentration, weight, or height between patients and
controls, significant differences were noted for Cd, Fe, Mg, Mn, Pb, Co, and Cu
(P <0.05). Conclusion: Our results suggest that heavy metals may play a causative
role in the development of chronic TE. However, contrary to previous reports,
zinc did not appear to play an important etiological role, while these patients
had elevated serum iron levels.
PMID- 29937563
TI - Retinol Levels in Serum and Chronic Skin Lesions of Atopic Dermatitis.
AB - Background: Atopic dermatitis (AD) is a common childhood dermatosis and a
distressing cause of morbidity. The pathogenesis of AD is known to be associated
with disorders of immune response and defect in antioxidant defense, genetic
predisposition, environmental triggers, psychosomatic factors, and other
mechanisms. Retinol has immunomodulatory and antioxidant effects, thus may have a
protective role in AD. Objective: The objective of this study was to evaluate the
correlation of retinol levels in skin lesions and serum, with AD. Materials and
Methods: The study was a hospital-based, case-control study. Punch biopsy from
the skin and venous blood of 86 participants (including 43 cases and 43 controls)
were assayed for retinol levels by a reversed-phase high-performance liquid
chromatography method. Analysis of data was performed using appropriate
statistical methods. Results: Skin and serum retinol levels were highly
significantly decreased in patients in respect to that of controls. Conclusion:
Retinol levels were decreased in AD. Retinol estimation may be used as a
promising parameter for the elaboration of treatment strategy and monitoring.
PMID- 29937564
TI - Low Vitamin D in Psoriasis: Reality or Myth?
AB - Context: Psoriasis is a chronic, systemic disease with the beneficial effect of
topical vitamin D3 analogs, known for a long time. Low levels of vitamin D are
increasingly found to be associated with the initial development of some
autoimmune diseases. There are contradictory reports of low serum levels of
vitamin D3 in the pathogenesis of psoriasis. Aims: (1) To determine the serum
levels of vitamin D, calcium and C-reactive protein (CRP) in patients with
psoriasis vulgaris, (2) To compare these levels with the serum levels of
controls, and (3) To correlate them with the severity of the disease. Subjects
and Methods: A hospital-based case-control study with 61 patients of psoriasis
and 61 age- and sex-matched controls was undertaken. A detailed history was taken
and examination including body mass index, Psoriasis Area and Severity Index
(PASI) was done. Estimations of serum vitamin D, serum calcium, and CRP levels
were done. Results: Mean 25(OH) vitamin D level was not significantly different
between persons with and without psoriasis. Mean vitamin D level in cases was
18.41+/-9.41 and that in controls was 17.24+/-13.03 (P =0.63). However, vitamin D
level were significantly lower in females than in males in both cases (P =0.02)
and controls (P =0.006). There was no significant correlation between the
severity of psoriasis and serum levels of vitamin D, serum calcium, and CRP.
Conclusions: Serum level of vitamin D did not correlate with the severity of
psoriasis in our study.
PMID- 29937565
TI - Reed's Syndrome.
AB - Multiple cutaneous and uterine leiomyomatosis (MCUL), also known as Reed's
syndrome, is a rare genodermatosis, with an autosomal dominant pattern of
inheritance. It results from a germline heterozygous mutation of fumarate
hydratase gene, that is classified as a tumor suppressor gene. Hereditary
leiomyomatosis and renal cell cancer is characterized by the association of MCUL
with renal cell carcinoma. We report a case of a 57-year-old woman, with multiple
cutaneous leiomyomas as the presenting sign of Reed's syndrome.
PMID- 29937566
TI - Interstitial Granulomatous Dermatitis due to a Rare Myeloproliferative Neoplasia.
AB - Interstitial granulomatous dermatitis (IGD) was first described in 1993 by
Ackerman as a cutaneous reactive disease in patients with arthritis. Since then,
numerous cases associated with different hematological and rheumatic disorders
have been reported. IGD is a polymorphic entity that usually involves the upper
part of the trunk. Histologically, it is defined as a diffuse dermal histiocytic
infiltrate of different densities surrounded by fragmented collagen. We report
the case of a 56-year-old man with pruritic papules affecting neck, proximal arms
and thorax associated with weight loss and chronic fatigue for six months. Two
punch biopsies were taken and the specimens showed lymphohistiocytic interstitial
infiltrates with fragmented collagen and elastic fibers in dermis. IGD was
diagnosed as first manifestation of a rare chronic myeloproliferative hematologic
disorder (cMPD) with rearrangement of beta-receptor for platelet-derived growth
factor (PDGFRB). After two months of imatinib, lesions regressed completely.
PMID- 29937567
TI - ANCA-associated Vasculitis in a Case of Congenital Leptin Deficiency.
PMID- 29937568
TI - Systemic Retinoids and Thyrotoxicosis in (Multi) Nodular Goiter: Side Effect or
Coincidence?
PMID- 29937569
TI - Onychomadesis: A Rare Skin Sign Occurring after Chickenpox.
PMID- 29937570
TI - Albendazole Induced Easy Bruising in a Patient of Hydatid Cyst of Liver.
PMID- 29937571
TI - Subcutaneous Left Cervical Nodule in an Infant Present since Birth.
PMID- 29937572
TI - Annular and Linear Brown Patches in Axillae.
PMID- 29937573
TI - Organic Synthesis: Wherefrom and Whither? (Some Very Personal Reflections).
AB - This perspective represents a (highly personal) examination of the past, present
and future of synthetic organic chemistry. The central thesis posits that the
confluence of factors that led to the "Golden Age of Natural Product Synthesis"
in the second half of the twentieth century can be traced back to the
identification of the therapeutic potential of steroid hormones culminating in
the introduction of oral contraceptives. The tremendous benefits of those
activities to the development of organic synthesis as a vibrant discipline led to
the exponential increase in strategies and methods and the ability to tackle,
larger and larger molecules of greater and greater complexity. The existential
challenge to the health of organic synthesis is whether a similarly dynamic
future can be anticipated and if so, to what end and how. Musings on potential
answers to those questions are presented.
PMID- 29937574
TI - Fluid flow measurement for diagnosis of ventricular shunt malfunction using
nonlinear responses of microbubbles in the contrast-enhanced ultrasound imaging.
AB - Contrast-enhanced ultrasound imaging utilizing the nonlinear responses of
microbubbles is proposed for identifying ventricular shunt malfunction. The
developed method suppresses the signal from walls of a shunt catheter and
background tissues, and allows accurate measurements of the cerebrospinal fluid
flow within the shunt catheter using a relatively small concentration of
microbubbles. The flow rates estimated in the linear mode were significantly
underestimated (65% at 0.1 ml/min and 5.0% microbubble concentration) while
estimates using the nonlinear mode were not. Overall, the nonlinear responses of
microbubbles improve the estimation of flow rates in a shunt catheter at low
concentrations of microbubbles.
PMID- 29937575
TI - Well Begun, But Aiming Higher: A Review of Vietnam's Education Trends in the Past
20 Years and Emerging Challenges.
AB - Given its modest position as a lower-middle income country, Vietnam stands out
from the rest of the world with its remarkable performance on standardized test
scores, school enrollment, and completed years of schooling. We provide an
overview of the factors behind this exemplary performance both from an
institutional viewpoint and by analyzing several different data sources, some of
which have rarely been used. Some of the highlights are universal primary school
enrollment, higher girls' net enrollment rates, and the role of within-commune
individual factors. We further discuss a host of challenges for the country-most
of which have received insufficient attention to date.
PMID- 29937576
TI - Eye Movements During Visual Speech Perception in Deaf and Hearing Children.
AB - For children who are born deaf, lipreading (speechreading) is an important source
of access to spoken language. We used eye tracking to investigate the strategies
used by deaf (n = 33) and hearing 5-8-year-olds (n = 59) during a sentence
speechreading task. The proportion of time spent looking at the mouth during
speech correlated positively with speechreading accuracy. In addition, all
children showed a tendency to watch the mouth during speech and watch the eyes
when the model was not speaking. The extent to which the children used this
communicative pattern, which we refer to as social-tuning, positively predicted
their speechreading performance, with the deaf children showing a stronger
relationship than the hearing children. These data suggest that better
speechreading skills are seen in those children, both deaf and hearing, who are
able to guide their visual attention to the appropriate part of the image and in
those who have a good understanding of conversational turn-taking.
PMID- 29937577
TI - Taxon-specific contributions to silica production in natural diatom assemblages.
AB - The metabolic activity and growth of phytoplankton taxa drives their ecological
function and contribution to biogeochemical processes. We present the first
quantitative, taxon-resolved silica production rates, growth rates, and silica
content estimates for co-occurring diatoms along two cross-shelf transects off
the California coast using the fluorescent tracer PDMPO (2-(4-pyridyl)-5-((4-(2
dimethylaminoethylaminocarbamoyl)methoxy)phenyl)oxazole), and confocal
microscopy. Taxon contribution to total diatom community silica production was
predominantly a function of the surface area of new frustule that each taxon
created as opposed to cell abundance or frustule thickness. The influential role
of surface area made large diatoms disproportionately important to community
silica production over short time scales (<1 d). In some cases, large taxa that
comprised only ~15% of numerical cell abundance accounted for over 50% of total
community silica production. Over longer time scales relevant to bloom dynamics,
the importance of surface area declines and growth rate becomes the dominant
influence on contribution to production. The relative importance of surface area
and growth rate in relation to silica production was modeled as the time needed
for a smaller, faster-growing taxon to create more surface area than a larger,
slower-growing taxon. Differences in growth rate between the taxa effected the
model outcome more than differences in surface area. Shifts in relative silica
production among taxa are time restricted by finite resources that limit the
duration of a bloom. These patterns offer clues as to how taxa respond to their
environment and the consequences for both species succession and the potential
diatom contribution to elemental cycling.
PMID- 29937578
TI - Avoiding timescale bias in assessments of coastal wetland vertical change.
AB - There is concern that accelerating sea-level rise will exceed the vertical growth
capacity of coastal-wetland substrates in many regions by the end of this
century. Vertical vulnerability estimates rely on measurements of accretion
and/or surface-elevation-change derived from soil cores and/or surface elevation
tables (SETs). To date there has not been a broad examination of whether the
multiple timescales represented by the processes of accretion and elevation
change are equally well-suited for quantifying the trajectories of wetland
vertical change in coming decades and centuries. To examine the potential for
timescale bias in assessments of vertical change, we compared rates of accretion
and surface elevation change using data derived from a review of the literature.
In the first approach, average rates of elevation change were compared with
timescale-averaged accretion rates from six regions around the world where sub
decadal, decadal, centennial, and millennial timescales were represented. Second,
to isolate spatial variability, temporal comparisons were made for regionally
unique environmental categories within each region. Last, comparisons were made
of records from sites where SET-MH stations and radiometric measurements were co
located in close proximity. We find that rates vary significantly as a function
of measurement timescale and that the pattern and magnitude of variation between
timescales are location-specific. Failure to identify and account for temporal
variability in rates will produce biased assessments of the vertical change
capacity of coastal wetlands. Robust vulnerability assessments should combine
accretion rates from multiple timescales with the longest available SET record to
provide long-term context for ongoing monitoring observations and projections.
PMID- 29937579
TI - Two-scale topology optimization in computational material design: An integrated
approach.
AB - In this work, a new strategy for solving multiscale topology optimization
problems is presented. An alternate direction algorithm and a precomputed offline
microstructure database (Computational Vademecum) are used to efficiently solve
the problem. In addition, the influence of considering manufacturable constraints
is examined. Then, the strategy is extended to solve the coupled problem of
designing both the macroscopic and microscopic topologies. Full details of the
algorithms and numerical examples to validate the methodology are provided.
PMID- 29937580
TI - Neurocranial anatomy of the petalichthyid placoderm Shearsbyaspis oepiki Young
revealed by X-ray computed microtomography.
AB - Stem-group gnathostomes reveal the sequence of character acquisition in the
origin of modern jawed vertebrates. The petalichthyids are placoderm-grade stem
group gnathostomes known from both isolated skeletal material and rarer
articulated specimens of one genus. They are of particular interest because of
anatomical resemblances with osteostracans, the jawless sister group of jawed
vertebrates. Because of this, they have become central to debates on the
relationships of placoderms and the primitive cranial architecture of
gnathostomes. However, among petalichthyids, only the braincase of
Macropetalichthys has been studied in detail, and the diversity of neurocranial
morphology in this group remains poorly documented. Using X-ray computed
microtomography, we investigated the endocranial morphology of Shearsbyaspis
oepiki Young, a three-dimensionally preserved petalichthyid from the Early
Devonian of Taemas-Wee Jasper, Australia. We generated virtual reconstructions of
the external endocranial surfaces, orbital walls and cranial endocavity,
including canals for major nerves and blood vessels. The neurocranium of
Shearsbyaspis resembles that of Macropetalichthys, particularly in the morphology
of the brain cavity, nerves and blood vessels. Many characters, including the
morphology of the pituitary vein canal and the course of the trigeminal nerve,
recall the morphology of osteostracans. Additionally, the presence of a
parasphenoid in Shearsbyaspis (previously not known with confidence outside of
arthrodires and osteichthyans) raises some questions about current proposals of
placoderm paraphyly. Our detailed description of this specimen adds to the known
morphological diversity of petalichthyids, and invites critical reappraisal of
the phylogenetic relationships of placoderms.
PMID- 29937581
TI - Characterization of the pathogenicity of strains of Pseudomonas syringae towards
cherry and plum.
AB - Bacterial canker is a major disease of Prunus avium (cherry), Prunus domestica
(plum) and other stone fruits. It is caused by pathovars within the Pseudomonas
syringae species complex including P. syringae pv. morsprunorum (Psm) race 1
(R1), Psm race 2 (R2) and P. syringae pv. syringae (Pss). Psm R1 and Psm R2 were
originally designated as the same pathovar; however, phylogenetic analysis
revealed them to be distantly related, falling into phylogroups 3 and 1,
respectively. This study characterized the pathogenicity of 18 newly genome
sequenced P. syringae strains on cherry and plum, in the field and laboratory.
The field experiment confirmed that the cherry cultivar Merton Glory exhibited a
broad resistance to all clades. Psm R1 contained strains with differential
specificity on cherry and plum. The ability of tractable laboratory-based assays
to reproduce assessments on whole trees was examined. Good correlations were
achieved with assays using cut shoots or leaves, although only the cut shoot
assay was able to reliably discriminate cultivar differences seen in the field.
Measuring bacterial multiplication in detached leaves differentiated pathogens
from nonpathogens and was therefore suitable for routine testing. In cherry
leaves, symptom appearance discriminated Psm races from nonpathogens, which
triggered a hypersensitive reaction. Pathogenic strains of Pss rapidly induced
disease lesions in all tissues and exhibited a more necrotrophic lifestyle than
hemibiotrophic Psm. This in-depth study of pathogenic interactions,
identification of host resistance and optimization of laboratory assays provides
a framework for future genetic dissection of host-pathogen interactions in the
canker disease.
PMID- 29937582
TI - A classification of response scale characteristics that affect data quality: a
literature review.
AB - Quite a lot of research is available on the relationships between survey response
scales' characteristics and the quality of responses. However, it is often
difficult to extract practical rules for questionnaire design from the wide and
often mixed amount of empirical evidence. The aim of this study is to provide
first a classification of the characteristics of response scales, mentioned in
the literature, that should be considered when developing a scale, and second a
summary of the main conclusions extracted from the literature regarding the
impact these characteristics have on data quality. Thus, this paper provides an
updated and detailed classification of the design decisions that matter in
questionnaire development, and a summary of what is said in the literature about
their impact on data quality. It distinguishes between characteristics that have
been demonstrated to have an impact, characteristics for which the impact has not
been found, and characteristics for which research is still needed to make a
conclusion.
PMID- 29937583
TI - Human values and beliefs and concern about climate change: a Bayesian
longitudinal analysis.
AB - The aim of this study was to investigate the influence of human values on beliefs
and concern about climate change using a longitudinal design and Bayesian
analysis. A sample of 298 undergraduate/master students filled out the same
questionnaire on two occasions at an interval of 2 months. The questionnaire
included measures of beliefs and concern about climate change (i.e., perceived
consequences, risk perception, and skepticism) and human values (i.e., the
Portrait Values Questionnaire). After controlling for gender and the respective
baseline score, universalism at Time 1 was associated with higher levels of
perceived consequences of climate change and lower levels of climate change
skepticism. Self-direction at Time 1 predicted Time 2 climate change risk
perception and perceived consequences of climate change. Hedonism at Time 1 was
associated with Time 2 climate change risk perception. The other human values at
Time 1 were not associated with any of the measures of beliefs and concern about
climate change at Time 2. The results of this study suggest that a focus on
universalism and self-direction values seems to be a more successful approach to
stimulate public engagement with climate change than a focus on other human
values.
PMID- 29937584
TI - Conflicting perceptions on participation between citizens and members of local
government.
AB - There is a growing consensus among citizens and members of local government that
citizen participation is desirable for local government. However in practice,
there are differing perceptions between them regarding the level and extent of
citizen participation. As citizen participation is a multi faceted concept, its
meaning is construed differently by both the members of local government and the
citizen groups. This paper attempts to describe the conflicts that arise from
participation. The paper is based on the study of the process of citizen
participation in local government carried out in Torbat-Heydarieh city, Iran. A
qualitative research method is seen as the most suitable approach of collecting
and analyzing the data. The method employed for data collection in this research
is in-depth interviews. In-depth interviews were conducted to gauge the existence
of conflicts regarding participation. The findings reveal four areas that give
rise to conflicts. This study also attempts to highlight two different views
regarding citizen participation; the people-centered view and authority-centered
view.
PMID- 29937585
TI - Saturation in qualitative research: exploring its conceptualization and
operationalization.
AB - Saturation has attained widespread acceptance as a methodological principle in
qualitative research. It is commonly taken to indicate that, on the basis of the
data that have been collected or analysed hitherto, further data collection
and/or analysis are unnecessary. However, there appears to be uncertainty as to
how saturation should be conceptualized, and inconsistencies in its use. In this
paper, we look to clarify the nature, purposes and uses of saturation, and in
doing so add to theoretical debate on the role of saturation across different
methodologies. We identify four distinct approaches to saturation, which differ
in terms of the extent to which an inductive or a deductive logic is adopted, and
the relative emphasis on data collection, data analysis, and theorizing. We
explore the purposes saturation might serve in relation to these different
approaches, and the implications for how and when saturation will be sought. In
examining these issues, we highlight the uncertain logic underlying saturation-as
essentially a predictive statement about the unobserved based on the observed, a
judgement that, we argue, results in equivocation, and may in part explain the
confusion surrounding its use. We conclude that saturation should be
operationalized in a way that is consistent with the research question(s), and
the theoretical position and analytic framework adopted, but also that there
should be some limit to its scope, so as not to risk saturation losing its
coherence and potency if its conceptualization and uses are stretched too widely.
PMID- 29937587
TI - Confounding and collinearity in regression analysis: a cautionary tale and an
alternative procedure, illustrated by studies of British voting behaviour.
AB - Many ecological- and individual-level analyses of voting behaviour use multiple
regressions with a considerable number of independent variables but few
discussions of their results pay any attention to the potential impact of inter
relationships among those independent variables-do they confound the regression
parameters and hence their interpretation? Three empirical examples are deployed
to address that question, with results which suggest considerable problems. Inter
relationships between variables, even if not approaching high collinearity, can
have a substantial impact on regression model results and how they are
interpreted in the light of prior expectations. Confounded relationships could be
the norm and interpretations open to doubt, unless considerable care is applied
in the analyses and an extended principal components method for doing that is
introduced and exemplified.
PMID- 29937586
TI - A mathematical approach to study and forecast racial groups interactions:
deterministic modeling and scenario method.
AB - Globalization and migratory fluxes are increasing the ethnic and racial diversity
within many countries. Therefore, describing social dynamics requires models that
are apt to capture multi-groups interactions. Building on the assumption of a
relationship between multi-racial dynamics and socioeconomic status (SES), we
introduce an aggregate, contextual, and continuous index of SES accounting for
measures of income, employment, expected life, and group numerosity. After,
taking into account that groups' SES assumes the form of a logit model, we
propose a Lotka-Volterra system to study and forecast the interaction among
racial groups. Last, we apply our methodology to describe the racial dynamics in
the US society. In particular, we study the kind and the intensity of Asians
Blacks-Natives-Whites interactions in the US between 2002 and 2013. Moreover, we
forecast the evolution of groups' SES and how interracial relations will unfold
between 2013 and 2018 and in three alternative stylized scenarios.
PMID- 29937588
TI - Periodic Auxetics: Structure and Design.
AB - Materials science has adopted the term of auxetic behavior for structural
deformations where stretching in some direction entails lateral widening, rather
than lateral shrinking. Most studies, in the last three decades, have explored
repetitive or cellular structures and used the notion of negative Poisson's ratio
as the hallmark of auxetic behavior. However, no general auxetic principle has
been established from this perspective. In the present article, we show that a
purely geometric approach to periodic auxetics is apt to identify essential
characteristics of frameworks with auxetic deformations and can generate a
systematic and endless series of periodic auxetic designs. The critical features
refer to convexity properties expressed through families of homothetic
ellipsoids.
PMID- 29937589
TI - Competitive Swimming and Racial Disparities in Drowning.
AB - This paper provides compelling evidence of an inverse relationship between
competitive swimming rates and drowning rates using Centers for Disease Control
and Prevention (CDC) data on fatal drowning rates and membership rates from USA
Swimming, the governing organization of competitive swimming in the United
States. Tobit and Poisson regression models are estimated using panel data by
state from 1999-2007 separately for males, females, African Americans and whites.
The strong inverse relationship between competitive swimming rates and
unintentional deaths through fatal drowning is most pronounced among African
Americans males.
PMID- 29937590
TI - The Production of Black Ph.D.'s in Economics at Harvard University, 1905-1955.
AB - Harvard University's Economics Department produced some of the leading African
American economists between World War I and the Korean War. This essay explores
the factors that contributed to this accomplishment and documents the career
trajectories of the six blacks who obtained the Doctorate in Economics from
Harvard University during the period 1905-1955. The analysis reveals the pivotal
roles of the Rosenwald Fund, Classical High Schools, Black Fraternal
Organizations and former University of Minnesota Applied Economics Professor,
John D. Black. A common outcome of the careers of these six pioneers was a
commitment to black economic empowerment.
PMID- 29937591
TI - An ensemble framework for time delay synchronization.
AB - Synchronization based state estimation tries to synchronize a model with the true
evolution of a system via the observations. In practice, an extra term is added
to the model equations which hampers growth of instabilities transversal to the
synchronization manifold. Therefore, there is a very close connection between
synchronization and data assimilation. Recently, synchronization with time
delayed observations has been proposed, in which observations at future times are
used to help synchronize a system that does not synchronize using only present
observations, with remarkable successes. Unfortunately, these schemes are limited
to small-dimensional problems. In this article, we lift that restriction by
proposing an ensemble-based synchronization scheme. Tests were performed using
the Lorenz'96 model for 20-, 100- and 1000-dimension systems. Results show global
synchronization errors stabilizing at values of at least an order of magnitude
lower than the observation errors, suggesting that the scheme is a promising tool
to steer model states to the truth. While this framework is not a complete data
assimilation method, we develop this methodology as a potential choice for a
proposal density in a more comprehensive data assimilation method, like a fully
nonlinear particle filter.
PMID- 29937592
TI - AN EVOLUTIONARY MODEL OF TUMOR CELL KINETICS AND THE EMERGENCE OF MOLECULAR
HETEROGENEITY DRIVING GOMPERTZIAN GROWTH.
AB - We describe a cell-molecular based evolutionary mathematical model of tumor
development driven by a stochastic Moran birth-death process. The cells in the
tumor carry molecular information in the form of a numerical genome which we
represent as a four-digit binary string used to differentiate cells into 16
molecular types. The binary string is able to undergo stochastic point mutations
that are passed to a daughter cell after each birth event. The value of the
binary string determines the cell fitness, with lower fit cells (e.g. 0000)
defined as healthy phenotypes, and higher fit cells (e.g. 1111) defined as
malignant phenotypes. At each step of the birth-death process, the two phenotypic
sub-populations compete in a prisoner's dilemma evolutionary game with the
healthy cells playing the role of cooperators, and the cancer cells playing the
role of defectors. Fitness, birth-death rates of the cell populations, and
overall tumor fitness are defined via the prisoner's dilemma payoff matrix.
Mutation parameters include passenger mutations (mutations conferring no fitness
advantage) and driver mutations (mutations which increase cell fitness). The
model is used to explore key emergent features associated with tumor development,
including tumor growth rates as it relates to intratumor molecular heterogeneity.
The tumor growth equation states that the growth rate is proportional to the
logarithm of cellular diversity/heterogeneity. The Shannon entropy from
information theory is used as a quantitative measure of heterogeneity and tumor
complexity based on the distribution of the 4-digit binary sequences produced by
the cell population. To track the development of heterogeneity from an initial
population of healthy cells (0000), we use dynamic phylogenetic trees which show
clonal and sub-clonal expansions of cancer cell sub-populations from an initial
malignant cell. We show tumor growth rates are not constant throughout tumor
development, and are generally much higher in the subclinical range than in later
stages of development, which leads to a Gompertzian growth curve. We explain the
early exponential growth of the tumor and the later saturation associated with
the Gompertzian curve which results from our evolutionary simulations using
simple statistical mechanics principles related to the degree of functional
coupling of the cell states. We then compare dosing strategies at early stage
development, mid-stage (clinical stage), and late stage development of the tumor.
If used early during tumor development in the subclinical stage, well before the
cancer cell population is selected for growth, therapy is most effective at
disrupting key emergent features of tumor development.
PMID- 29937593
TI - Application of one-step method to parameter estimation in ODE models.
AB - In this paper, we study application of Le Cam's one-step method to parameter
estimation in ordinary differential equation models. This computationally simple
technique can serve as an alternative to numerical evaluation of the popular non
linear least squares estimator, which typically requires the use of a multistep
iterative algorithm and repetitive numerical integration of the ordinary
differential equation system. The one-step method starts from a preliminary n
consistent estimator of the parameter of interest and next turns it into an
asymptotic (as the sample size n->infinity) equivalent of the least squares
estimator through a numerically straightforward procedure. We demonstrate
performance of the one-step estimator via extensive simulations and real data
examples. The method enables the researcher to obtain both point and interval
estimates. The preliminary n -consistent estimator that we use depends on non
parametric smoothing, and we provide a data-driven methodology for choosing its
tuning parameter and support it by theory. An easy implementation scheme of the
one-step method for practical use is pointed out.
PMID- 29937594
TI - Synthesis of 2-Alkenyl-Tethered Anilines.
AB - Three general routes for the synthesis of (E)-2-alkenyl-tethered anilines have
been developed. The first route involves a 3-aza-Cope rearrangement of N-allylic
anilines in the presence of a Lewis acid. The requisite N-allylic anilines were
prepared by the addition of vinyl-magnesium reagents to the corresponding
aldimines. The second route details a direct cross-metathesis of 2-allylic or 2
homoallylic anilines with styrenes. The third route involves a palladium
catalyzed C-N cross-coupling of aryl halides. Taken together, these three
strategies allowed access to the requisite aniline substrates with pendant
alkenes at the 2-position with excellent trans selectivities.
PMID- 29937595
TI - Defining the habitat niche of Alopecurus myosuroides at the field scale.
AB - The distribution of Alopecurus myosuroides (black-grass) in fields is patchy. The
locations of these patches can be influenced by the environment. This presents an
opportunity for precision management through patch spraying. We surveyed five
fields on various types of soil using a nested sampling design and recorded both
A. myosuroides seedlings in autumn and seed heads in summer. We also measured
soil properties at those sampling locations. We found that the patches of seed
heads within a field were smaller than the seedling patches, suggesting that
techniques for patch spraying based on maps of heads in the previous season could
be inherently risky. We also found that the location of A. myosuroides patches
within fields can be predicted through their relationship with environmental
properties and that these relations are consistent across fields on different
soil types. This improved understanding of the relations between soil properties
and A. myosuroides seedlings could allow farmers to use pre-existing or suitably
supplemented soil maps already in use for the precision application of
fertilisers as a starting point in the creation of herbicide application maps.
PMID- 29937596
TI - Plankton metacommunities in floodplain wetlands under contrasting hydrological
conditions.
AB - Species diversity is affected by processes operating at multiple spatial scales,
although the most relevant scales that contribute to compositional variation and
the temporal shifts of the involved mechanisms remain poorly explored. We studied
spatial patterns of phytoplankton, rotifers and microcrustacean diversity across
scales in a river floodplain system of the Danube in Austria under contrasting
hydrological conditions (post-flood versus low water level).The species turnover
between water sections (beta2) and between wetlands (beta3) was the major
components of regional diversity for all studied groups, with species turnover
between habitats (beta1) as a minor contributor. beta1 diversity and beta2
diversity were lower than expected by chance in most cases, suggesting that
communities are more homogeneous than expected at these scales. beta3 diversity
was higher than expected by chance in many cases, indicating more distinct
communities at the wetland level. Patterns were highly similar under different
hydrological conditions, indicating no major immediate effect of flood
events.Local environmental and spatial factors were similarly important in
structuring phytoplankton, rotifer and microcrustacean communities in both
hydrological conditions. Relevant environmental factors were spatially structured
in post-flood conditions especially between sections, suggesting flood-driven
homogenisation within the wetlands. Under low water level, spatial structuring of
environment decreased and pure environmental factors gained relevance for
phytoplankton and rotifers.Our results suggest that although beta2 diversity
between water sections is a major component of regional diversity, long-term
spatial processes responding to connectivity across the wetland structure
phytoplankton, rotifer and microcrustacean communities. Aquatic sections within
the limited spatial extent of the remaining floodplain areas appear more
homogeneous than expected probably due to flood recurrence over the years.These
results highlight that adequate planning of restoration and conservation
strategies of floodplain wetlands should consider environmental heterogeneity
together with long-term spatial processes.
PMID- 29937597
TI - Synthetic Iron Oxides for Adsorptive Removal of Arsenic.
AB - Removal of arsenic from water reservoirs is the issue of great concern in many
places around the globe. As adsorption is one of the most efficient techniques
for treatment of As-containing media, thus the present study concerns application
of iron oxides-hydroxides (akaganeite) as adsorbents for removal of this harmful
metal from aqueous solution. Two types of akaganeite were tested: synthetic one
(A) and the same modified using hexadecyltrimethylammonium bromide (AM). Removal
of As was tested in batch studies in function of pH, adsorbent dosage, contact
time, and initial arsenic concentration. The adsorption isotherms obey Langmuir
mathematical model. Adsorption kinetics complies with pseudo-second-order kinetic
model, and the constant rates were defined as 2.07 * 10-3and 0.92 * 10-3 g mg-1
min-1 for the samples (A) and (AM), respectively. The difference was caused by
significant decrease in adsorption rate in initial state of the process carried
out for the sample AM. The maximum adsorption capacity achieved for (A) and (AM)
akaganeite taken from Langmuir isotherm was 148.7 and 170.9 mg g-1, respectively.
The results suggest that iron oxides-hydroxides can be used for As removal from
aqueous solutions.
PMID- 29937598
TI - Polycyclic Aromatic Hydrocarbons Content in Contaminated Forest Soils with
Different Humus Types.
AB - The aim of the study was to determine polycyclic aromatic hydrocarbon (PAH)
content in different forest humus types. The investigation was carried out in
Chrzanow Forest District in southern Poland. Twenty research plots with different
humus types (mor and mull) were selected. The samples for analysis were taken
after litter horizons removing from a depth of 0-10 cm (from the Of- and Oh
horizon total or A-horizon). pH, organic carbon and total nitrogen content, base
cations, acidity, and heavy metal content were determined. In the natural
moisture state, the activity of dehydrogenase was determined. The study included
the determination of PAH content. The conducted research confirms strong
contamination of study soil by PAHs and heavy metals. Our experiment provided
evidence that different forest humus types accumulate different PAH amounts. The
highest content of PAHs and heavy metals was recorded in mor humus type. The
content of PAHs in forest humus horizon depends on the content and quality of
soil organic matter. Weaker degradation of hydrocarbons is associated with lower
biological activity of soils. The mull humus type showed lower content of PAHs
and at the same time the highest biological activity confirmed by high
dehydrogenase activity.
PMID- 29937600
TI - Fast Adjustments of the Asian Summer Monsoon to Anthropogenic Aerosols.
AB - Anthropogenic aerosols are a major factor contributing to human-induced climate
change, particularly over the densely populated Asian monsoon region.
Understanding the physical processes controlling the aerosol-induced changes in
monsoon rainfall is essential for reducing the uncertainties in the future
projections of the hydrological cycle. Here we use multiple coupled and
atmospheric general circulation models to explore the physical mechanisms for the
aerosol-driven monsoon changes on different time scales. We show that
anthropogenic aerosols induce an overall reduction in monsoon rainfall and
circulation, which can be largely explained by the fast adjustments over land
north of 20?N. This fast response occurs before changes in sea surface
temperature (SST), largely driven by aerosol-cloud interactions. However, aerosol
induced SST feedbacks (slow response) cause substantial changes in the monsoon
meridional circulation over the oceanic regions. Both the land-ocean asymmetry
and meridional temperature gradient are key factors in determining the overall
monsoon circulation response.
PMID- 29937599
TI - A review of polymeric membranes and processes for potable water reuse.
AB - Conventional water resources in many regions are insufficient to meet the water
needs of growing populations, thus reuse is gaining acceptance as a method of
water supply augmentation. Recent advancements in membrane technology have
allowed for the reclamation of municipal wastewater for the production of
drinking water, i.e., potable reuse. Although public perception can be a
challenge, potable reuse is often the least energy-intensive method of providing
additional drinking water to water stressed regions. A variety of membranes have
been developed that can remove water contaminants ranging from particles and
pathogens to dissolved organic compounds and salts. Typically, potable reuse
treatment plants use polymeric membranes for microfiltration or ultrafiltration
in conjunction with reverse osmosis and, in some cases, nanofiltration. Membrane
properties, including pore size, wettability, surface charge, roughness, thermal
resistance, chemical stability, permeability, thickness and mechanical strength,
vary between membranes and applications. Advancements in membrane technology
including new membrane materials, coatings, and manufacturing methods, as well as
emerging membrane processes such as membrane bioreactors, electrodialysis, and
forward osmosis have been developed to improve selectivity, energy consumption,
fouling resistance, and/or capital cost. The purpose of this review is to provide
a comprehensive summary of the role of polymeric membranes in the treatment of
wastewater to potable water quality and highlight recent advancements in
separation processes. Beyond membranes themselves, this review covers the
background and history of potable reuse, and commonly used potable reuse process
chains, pretreatment steps, and advanced oxidation processes. Key trends in
membrane technology include novel configurations, materials and fouling
prevention techniques. Challenges still facing membrane-based potable reuse
applications, including chemical and biological contaminant removal, membrane
fouling, and public perception, are highlighted as areas in need of further
research and development.
PMID- 29937601
TI - Fat Plumes May Reflect the Complex Rheology of the Lower Mantle.
AB - Recent tomographic imaging of the mantle below major hot spots shows slow seismic
velocities extending down to the core-mantle boundary, confirming the existence
of mantle plumes. However, these plumes are much thicker than previously thought.
Using new laboratory experiments and scaling laws, we show that thermal plumes
developing in a visco-plastic fluid present much larger diameters than plumes
developing in a Newtonian fluid. Such a rheology requiring a yield stress is
consistent with a lower mantle predominantly deforming by pure dislocation climb.
Yield stress values between 1 and 10 MPa, implying dislocation densities between
108 and 1010 m-2, would be sufficient to reproduce the plumes morphology observed
in tomographic images.
PMID- 29937602
TI - Irrigation as a Potential Driver for Anomalous Glacier Behavior in High Mountain
Asia.
AB - Many glaciers in the northwest of High Mountain Asia (HMA) show an almost zero or
positive mass balance, despite the global trend of melting glaciers. This
phenomenon is often referred to as the "Karakoram anomaly," although strongest
positive mass balances can be found in the Kunlun Shan mountain range, northeast
of the Karakoram. Using a regional climate model, in combination with a moisture
tracking model, we show that the increase in irrigation intensity in the lowlands
surrounding HMA, particularly in the Tarim basin, can locally counter the effects
of global warming on glaciers in Kunlun Shan, and parts of Pamir and northern
Tibet, through an increase in summer snowfall and decrease in net radiance.
Irrigation can thus affect the regional climate in a way that favors glacier
growth, and future projections of glacier melt, which may impact millions of
inhabitants surrounding HMA, will need to take into account predicted changes in
irrigation intensity.
PMID- 29937603
TI - Spatial Representativeness Error in the Ground-Level Observation Networks for
Black Carbon Radiation Absorption.
AB - There is high uncertainty in the direct radiative forcing of black carbon (BC),
an aerosol that strongly absorbs solar radiation. The observation-constrained
estimate, which is several times larger than the bottom-up estimate, is
influenced by the spatial representativeness error due to the mesoscale
inhomogeneity of the aerosol fields and the relatively low resolution of global
chemistry-transport models. Here we evaluated the spatial representativeness
error for two widely used observational networks (AErosol RObotic NETwork and
Global Atmosphere Watch) by downscaling the geospatial grid in a global model of
BC aerosol absorption optical depth to 0.1 degrees * 0.1 degrees . Comparing the
models at a spatial resolution of 2 degrees * 2 degrees with BC aerosol
absorption at AErosol RObotic NETwork sites (which are commonly located near
emission hot spots) tends to cause a global spatial representativeness error of
30%, as a positive bias for the current top-down estimate of global BC direct
radiative forcing. By contrast, the global spatial representativeness error will
be 7% for the Global Atmosphere Watch network, because the sites are located in
such a way that there are almost an equal number of sites with positive or
negative representativeness error.
PMID- 29937604
TI - Vulnerability of Southeast Greenland Glaciers to Warm Atlantic Water From
Operation IceBridge and Ocean Melting Greenland Data.
AB - We employ National Aeronautics and Space Administration (NASA)'s Operation
IceBridge high-resolution airborne gravity from 2016, NASA's Ocean Melting
Greenland bathymetry from 2015, ice thickness from Operation IceBridge from 2010
to 2015, and BedMachine v3 to analyze 20 major southeast Greenland glaciers. The
results reveal glacial fjords several hundreds of meters deeper than previously
thought; the full extent of the marine-based portions of the glaciers; deep
troughs enabling warm, salty Atlantic Water (AW) to reach the glacier fronts and
melt them from below; and few shallow sills that limit the access of AW. The new
oceanographic and topographic data help to fully resolve the complex pattern of
historical ice front positions from the 1930s to 2017: glaciers exposed to AW and
resting on retrograde beds have retreated rapidly, while glaciers perched on
shallow sills or standing in colder waters or with major sills in the fjords have
remained stable.
PMID- 29937605
TI - A Century of Stability of Avannarleq and Kujalleq Glaciers, West Greenland,
Explained Using High-Resolution Airborne Gravity and Other Data.
AB - The evolution of Greenland glaciers in a warming climate depends on their depth
below sea level, flow speed, surface melt, and ocean-induced undercutting at the
calving front. We present an innovative mapping of bed topography in the frontal
regions of Sermeq Avannarleq and Kujalleq, two major glaciers flowing into the
ice-choked Torssukatak Fjord, central west Greenland. The mapping combines a mass
conservation algorithm inland, multibeam echo sounding data in the fjord, and
high-resolution airborne gravity data at the ice-ocean transition where other
approaches have traditionally failed. We obtain a reliable, precision (+/-40 m)
solution for bed topography across the ice-ocean boundary. The results reveal a
700 m deep fjord that abruptly ends on a 100-300 m deep sill along the calving
fronts. The shallow sills explain the presence of stranded icebergs, the
resilience of the glaciers to ocean-induced undercutting by warm Atlantic water,
and their remarkable stability over the past century.
PMID- 29937606
TI - Unprecedented 2015/2016 Indo-Pacific Heat Transfer Speeds Up Tropical Pacific
Heat Recharge.
AB - El Nino events are characterized by anomalously warm tropical Pacific surface
waters and concurrent ocean heat discharge, a precursor of subsequent cold La
Nina conditions. Here we show that El Nino 2015/2016 departed from this norm:
despite extreme peak surface temperatures, tropical Pacific (30 degrees N-30
degrees S) upper ocean heat content increased by 9.6 +/- 1.7 ZJ (1 ZJ = 1021 J),
in stark contrast to the previous strong El Nino in 1997/1998 (-11.5 +/- 2.9 ZJ).
Unprecedented reduction of Indonesian Throughflow volume and heat transport
played a key role in the anomalous 2015/2016 event. We argue that this anomaly is
linked with the previously documented intensified warming and associated rising
sea levels in the Indian Ocean during the last decade. Additionally, increased
absorption of solar radiation acted to dampen Pacific ocean heat content
discharge. These results explain the weak and short-lived La Nina conditions in
2016/2017 and indicate the need for realistic representation of Indo-Pacific
energy transfers for skillful seasonal-to-decadal predictions.
PMID- 29937607
TI - Bayesian Analysis of the Glacial-Interglacial Methane Increase Constrained by
Stable Isotopes and Earth System Modeling.
AB - The observed rise in atmospheric methane (CH4) from 375 ppbv during the Last
Glacial Maximum (LGM: 21,000 years ago) to 680 ppbv during the late preindustrial
era is not well understood. Atmospheric chemistry considerations implicate an
increase in CH4 sources, but process-based estimates fail to reproduce the
required amplitude. CH4 stable isotopes provide complementary information that
can help constrain the underlying causes of the increase. We combine Earth System
model simulations of the late preindustrial and LGM CH4 cycles, including process
based estimates of the isotopic discrimination of vegetation, in a box model of
atmospheric CH4 and its isotopes. Using a Bayesian approach, we show how model
based constraints and ice core observations may be combined in a consistent
probabilistic framework. The resultant posterior distributions point to a strong
reduction in wetland and other biogenic CH4 emissions during the LGM, with a
modest increase in the geological source, or potentially natural or anthropogenic
fires, accounting for the observed enrichment of delta13CH4.
PMID- 29937608
TI - Warming and Inhibition of Salinization at the Ocean's Surface by Cyanobacteria.
AB - This paper describes high-resolution in situ observations of temperature and, for
the first time, of salinity in the uppermost skin layer of the ocean, including
the influence of large surface blooms of cyanobacteria on those skin properties.
In the presence of the blooms, large anomalies of skin temperature and salinity
of 0.95 degrees C and -0.49 practical salinity unit were found, but a
substantially cooler (-0.22 degrees C) and saltier skin layer (0.19 practical
salinity unit) was found in the absence of surface blooms. The results suggest
that biologically controlled warming and inhibition of salinization of the
ocean's surface occur. Less saline skin layers form during precipitation, but our
observations also show that surface blooms of Trichodesmium sp. inhibit
evaporation decreasing the salinity at the ocean's surface. This study has
important implications in the assessment of precipitation over the ocean using
remotely sensed salinity, but also for a better understanding of heat exchange
and the hydrologic cycle on a regional scale.
PMID- 29937609
TI - Education and Health: Redrawing the Preston Curve.
PMID- 29937610
TI - Surface Chemistry of Thermal Dry Etching of Cobalt Thin Films Using
Hexafluoroacetylacetone (hfacH).
AB - Amechanism of thermal dry etching process of cobalt thin films by using
1,1,1,5,5,5-hexafluoro-2,4-pentanedione (hexafluoroacetylacetone, hfacH) was
investigated. This process, relevant to atomic layer etching (ALE) technology
directed towards oxidized cobalt films, requires adsorption of molecular organic
precursor, such as hfacH, at moderate temperatures and is often thought of as
releasing water and Co(hfac)2 at elevated temperatures. The reaction was analyzed
in situ by temperature-programmed desorption (TPD) and the resulting surface was
investigated ex situ by X-ray photoelectron spectroscopy (XPS). The changes in
surface morphology during the process were monitored by atomic force microscopy
(AFM) and scanning electron microscopy (SEM). The removal of Co(hfac)2 from the
surface was observed above 650 K, a temperature well above commercially desired
etching conditions, suggesting that the thermal etching process is more complex
than originally envisioned. In addition, the upper limit of thermal treatment is
established at 800 K, as the microscopic techniques clearly indicated surface
morphology changes above this temperature. In addition, the structure of the
surface at the nanoscale is observed to be affected by the presence of surface
bound organic ligands even at room temperature. Thus, further mechanistic studies
should address the kinetic regime and surface morphology to make inroads into
mechanistic understanding of the dry etching process.
PMID- 29937611
TI - Complexity of Secure Sets.
AB - A secure set S in a graph is defined as a set of vertices such that for any X?S
the majority of vertices in the neighborhood of X belongs to S. It is known that
deciding whether a set S is secure in a graph is co-NP -complete. However, it is
still open how this result contributes to the actual complexity of deciding
whether for a given graph G and integer k, a non-empty secure set for G of size
at most k exists. In this work, we pinpoint the complexity of this problem by
showing that it is Sigma2P -complete. Furthermore, the problem has so far not
been subject to a parameterized complexity analysis that considers structural
parameters. In the present work, we prove that the problem is W[1] -hard when
parameterized by treewidth. This is surprising since the problem is known to be
FPT when parameterized by solution size and "subset problems" that satisfy this
property usually tend to be FPT for bounded treewidth as well. Finally, we give
an upper bound by showing membership in XP , and we provide a positive result in
the form of an FPT algorithm for checking whether a given set is secure on graphs
of bounded treewidth.
PMID- 29937612
TI - A qualitative investigation of childbearing and seasonal hunger in peri-urban
Ouagadougou, Burkina Faso.
AB - Poor women who live in peri-urban communities are often faced with food
insecurity due to seasonal variations in food availability and accessibility.
Additionally, in these communities, fertility levels are often elevated despite
geographic proximity to urban areas with low cost contraception. We conducted
five focus group interviews to investigate the lived experiences of childbearing
in peri-urban Ouagadougou, Burkina Faso to understand the behavioral and
biological determinants of fertility outcomes. In the analysis of the interviews
we pay particular attention to seasonal food insecurity experiences and the
biological and behavioral determinants of childbearing. Our results suggest that
there are less optimal times of year for childbearing and that poor, peri-urban
women adjust their behavior accordingly. The results also suggest that there
remain important barriers to contraceptive use even in cases where individuals
associate pregnancy and childbearing with physical and psychological risk. This
paper provides greater depth in understanding the determinants of fertility in
resource-poor, peri-urban communities and points to some barriers for lowering
fertility in similar areas.
PMID- 29937613
TI - Does Child Sponsorship Pay Off In Adulthood? An International Study of Impacts on
Income and Wealth.
AB - We estimate the impact of international child sponsorship on adult income and
wealth of formerly sponsored children using data on 10,144 individuals in six
countries. To identify causal effects, we utilize an age-eligibility rule
followed from 1980 to 1992 that limited sponsorship to children 12 years old or
younger when the program was introduced in a village, allowing comparisons of
sponsored children with older siblings who were slightly too old to be sponsored.
Estimations indicate that international child sponsorship increased monthly
income by $13-17 over an untreated baseline of $75, principally from inducing
higher future labor market participation. We find evidence for positive impacts
on dwelling quality in adulthood, and modest evidence of impacts on ownership of
consumer durables in adulthood, limited to increased ownership of mobile phones.
Finally, our results also show modest effects of child sponsorship on
childbearing in adulthood.
PMID- 29937614
TI - Thermal limits in native and alien freshwater peracarid Crustacea: The role of
habitat use and oxygen limitation.
AB - In order to predict which species can successfully cope with global warming and
how other environmental stressors modulate their vulnerability to climate-related
environmental factors, an understanding of the ecophysiology underpinning thermal
limits is essential for both conservation biology and invasion biology.Heat
tolerance and the extent to which heat tolerance differed with oxygen
availability were examined for four native and four alien freshwater peracarid
crustacean species, with differences in habitat use across species. Three
hypotheses were tested: (1) Heat and lack of oxygen synergistically reduce
survival of species; (2) patterns in heat tolerance and the modulation thereof by
oxygen differ between alien and native species and between species with different
habitat use; (3) small animals can better tolerate heat than large animals, and
this difference is more pronounced under hypoxia.To assess heat tolerances under
different oxygen levels, animal survival was monitored in experimental chambers
in which the water temperature was ramped up (0.25 degrees C min-1). Heat
tolerance (CTmax) was scored as the cessation of all pleopod movement, and
heating trials were performed under hypoxia (5 kPa oxygen), normoxia (20 kPa) and
hyperoxia (60 kPa).Heat tolerance differed across species as did the extent by
which heat tolerance was affected by oxygen conditions. Heat-tolerant species,
for example, Asellus aquaticus and Crangonyx pseudogracilis, showed little
response to oxygen conditions in their CTmax, whereas the CTmax of heat-sensitive
species, for example, Dikerogammarus villosus and Gammarus fossarum, was more
plastic, being increased by hyperoxia and reduced by hypoxia.In contrast to other
studies on crustaceans, alien species were not more heat-tolerant than native
species. Instead, differences in heat tolerance were best explained by habitat
use, with species from standing waters being heat tolerant and species from
running waters being heat sensitive. In addition, larger animals displayed lower
critical maximum temperature, but only under hypoxia. An analysis of data
available in the literature on metabolic responses of the study species to
temperature and oxygen conditions suggests that oxygen conformers and species
whose oxygen demand rapidly increases with temperature (low activation energy)
may be more heat sensitive.The alien species D. villosus appeared most
susceptible to hypoxia and heat stress. This may explain why this species is very
successful in colonizing new areas in littoral zones with rocky substrate which
are well aerated due to continuous wave action generated by passing ships or
prevailing winds. This species is less capable of spreading to other waters which
are poorly oxygenated and where C. pseudogracilis is the more likely dominant
alien species. A http://onlinelibrary.wiley.com/doi/10.1111/1365
2435.13050/suppinfo is available for this article.
PMID- 29937615
TI - Automated classification and quantitative analysis of arterial and venous vessels
in fundus images.
AB - It is known that retinopathies may affect arteries and veins differently.
Therefore, reliable differentiation of arteries and veins is essential for
computer-aided analysis of fundus images. The purpose of this study is to
validate one automated method for robust classification of arteries and veins (A
V) in digital fundus images. We combine optical density ratio (ODR) analysis and
blood vessel tracking algorithm to classify arteries and veins. A matched
filtering method is used to enhance retinal blood vessels. Bottom hat filtering
and global thresholding are used to segment the vessel and skeleton individual
blood vessels. The vessel tracking algorithm is used to locate the optic disk and
to identify source nodes of blood vessels in optic disk area. Each node can be
identified as vein or artery using ODR information. Using the source nodes as
starting point, the whole vessel trace is then tracked and classified as vein or
artery using vessel curvature and angle information. 50 color fundus images from
diabetic retinopathy patients were used to test the algorithm. Sensitivity,
specificity, and accuracy metrics were measured to assess the validity of the
proposed classification method compared to ground truths created by two
independent observers. The algorithm demonstrated 97.52% accuracy in identifying
blood vessels as vein or artery. A quantitative analysis upon A-V classification
showed that average A-V ratio of width for NPDR subjects with hypertension
decreased significantly (43.13%).
PMID- 29937616
TI - Investigation of organ dose variation with adult head size and pediatric age for
neuro-interventional projections.
AB - The purpose of this study was to evaluate the effect of patient head size on
radiation dose to radiosensitive organs, such as the eye lens, brain and spinal
cord in fluoroscopically guided neuro-interventional procedures and CBCT scans of
the head. The Toshiba Infinix C-Arm System was modeled in BEAMnrc/EGSnrc Monte
Carlo code and patient organ and effective doses were calculated in
DOSxynrc/EGSnrc for CBCT and interventional procedures. X-ray projections from
different angles, CBCT scans, and neuro-interventional procedures were simulated
on a computational head phantom for the range of head sizes in the adult
population and for different pediatric ages. The difference of left-eye lens dose
between the mean head size and the mean +/- 1 standard deviation (SD) ranges from
20% to 300% for projection angles of 0 degrees to 90 degrees RAO. The
differences for other organs do not vary as much and is only about 10% for the
brain. For a LCI-High CBCT protocol, the difference between mean and mean +/- 1
SD head size is about 100% for lens dose and only 10% for mean and peak brain
dose; the difference between 20 and 3 year-old mean head size is an increase of
about 200% for the eye lens dose and only 30% for mean and peak brain dose. Dose
for all organs increases with decreasing head size for the same reference point
air kerma. These results will allow size-specific dose estimates to be made using
software such as our dose tracking system (DTS).
PMID- 29937617
TI - The institutional workers of biomedical science: Legitimizing academic
entrepreneurship and obscuring conflicts of interest.
AB - Given growing initiatives incentivizing academic researchers to engage in
'entrepreneurial' activities, this article examines how these academic
entrepreneurs claim value in their entrepreneurial engagements, and navigate
concerns related to conflicts of interest. Using data from qualitative interviews
with twenty-four academic entrepreneurs in Canada, we show how these scientists
value entrepreneurial activities for providing financial and intellectual
resources to academic science, as well as for their potential to create impact
through translation. Simultaneously, these scientists claimed to maintain
academic norms of disinterested science and avoid conflicts of interest. Using
theories of institutional work, we demonstrate how entrepreneurial scientists
engage in processes of institutional change-through-maintenance, drawing on the
maintenance of academic norms as institutional resources to legitimize
entrepreneurial activities. As entrepreneurial scientists work to legitimize new
zones of academic scientific practice, there is a need to carefully regulate and
scrutinize these activities so that their potential harms do not become obscured.
PMID- 29937618
TI - Fonduer: Knowledge Base Construction from Richly Formatted Data.
AB - We focus on knowledge base construction (KBC) from richly formatted data. In
contrast to KBC from text or tabular data, KBC from richly formatted data aims to
extract relations conveyed jointly via textual, structural, tabular, and visual
expressions. We introduce Fonduer, a machine-learning-based KBC system for richly
formatted data. Fonduer presents a new data model that accounts for three
challenging characteristics of richly formatted data: (1) prevalent document
level relations, (2) multimodality, and (3) data variety. Fonduer uses a new deep
learning model to automatically capture the representation (i.e., features)
needed to learn how to extract relations from richly formatted data. Finally,
Fonduer provides a new programming model that enables users to convert domain
expertise, based on multiple modalities of information, to meaningful signals of
supervision for training a KBC system. Fonduer-based KBC systems are in
production for a range of use cases, including at a major online retailer. We
compare Fonduer against state-of-the-art KBC approaches in four different
domains. We show that Fonduer achieves an average improvement of 41 F1 points on
the quality of the output knowledge base-and in some cases produces up to 1.87*
the number of correct entries-compared to expert-curated public knowledge bases.
We also conduct a user study to assess the usability of Fonduer's new programming
model. We show that after using Fonduer for only 30 minutes, non-domain experts
are able to design KBC systems that achieve on average 23 F1 points higher
quality than traditional machine-learning-based KBC approaches.
PMID- 29937619
TI - Using the Annual Social and Economic Supplement as Part of a Current Population
Survey Panel.
AB - The Annual Social and Economic Supplement (ASEC) is the most widely used type of
Current Population Survey (CPS) data, but it is cumbersome to use the ASEC as
part of a longitudinal CPS panel, especially linking to non-March months. In this
paper, we detail the challenges associated with linking the ASEC to monthly CPS
data, outline the creation of an identifier that links the ASEC and the March
Basic Monthly data from 1989 through 2017, and provide substantive examples that
illustrate the value of combining the ASEC with monthly data. The variable,
MARBASECID, which we created to link ASEC and March monthly CPS data, represents
a significant contribution to social and economic data infrastructure, saving
individual researchers from having to duplicate the effort required to create
linkages between ASEC and monthly CPS data.
PMID- 29937620
TI - Dutch Norms for the Eyberg Child Behavior Inventory: Comparisons with other
Western Countries.
AB - The Eyberg Child Behavior Inventory (ECBI) is one of the most widely used and
well-validated parent rating scales for children's disruptive behavior. This
screening instrument is a short, targetted and easy to implement inventory with
good psychometric properties and is normed for different countries, among which
the United States, Spain, Sweden and Norway. The ECBI has been successfully used
for research and clinical purposes, in several countries including The
Netherlands. To date, Dutch studies have relied on Scandinavian or US norm
scores. However, this may be problematic because of cross-cultural differences in
the degree to which certain behaviors are seen as problematic by parents. The
main goal of this paper therefore was to obtain norm scores for The Netherlands
among 6462 Dutch children aged 4 to 8 years (Mage = 6.37 years; SD = 1.32; 50.6%
boys). In line with previous research, we found small differences on the mean sum
scores across children of different ages (intensity scale) and gender (intensity
and problem scale). Therefore, Dutch norm scores were provided age- and gender
specific. Our results showed that disruptive behavior of children in the most
rural areas was reported as occurring less frequently and was seen as less
problematic by parents compared to the disruptive behavior of children in less
rural areas. Finally, we found that Dutch norm scores on the ECBI were
significantly lower than US norm scores, and significantly higher on the
intensity scale (but not the problem scale) than Norwegian and Swedish norm
scores.
PMID- 29937621
TI - Intraindividual Dynamic Network Analysis - Implications for Clinical Assessment.
AB - A network analysis approach to psychopathology regards symptoms as mutually
interacting components of a multifaceted system (Borsboom & Cramer, 2013).
Although several studies using this approach have examined comorbidity between
disorders using cross-sectional samples, a direct application of the network
analysis approach to intraindividual dynamic relations between symptoms in a
complex, comorbid case has not been reported. The current article describes an
intraindividual dynamic network analysis (IDNA) approach to understanding the
psychopathology of an individual using dynamic (over time) lead-lag
interrelations between symptoms. Multivariate time series data were utilized to
create and examine an intraindividual, lag-1 network of the partial, day-to-day
relations of symptoms in an individual with comorbid mood and anxiety disorders.
Characteristics of the network, including centrality indices, stability, dynamic
processes between symptoms, and their implications for clinical assessment are
described. Additional clinical implications and future directions for IDNA,
including the potential incremental validity of this assessment approach for
empirically-based idiographic assessment and personalized treatment planning, are
discussed. This person-specific IDNA approach may be especially useful in complex
and comorbid cases.
PMID- 29937622
TI - Reliable and Valid Coding of Thin Slices of Video Footage: Applicability to the
Assessment of Mother-Child Interactions.
AB - When using behavioral-observation methods for coding video footage, it is unknown
how much time of an interaction needs to be coded to gain results that are
representative for the behavior of interest. The current study examined this
problem using the INTAKT, a standardized observational measure for assessing the
quality of mother-child interactions. Results from coding only 10 min of each
video (i.e., thin slices) were compared with results from coding the remaining
parts (averaging about 40 min) of the interaction. Inter-rater agreement for the
short versions taken from the beginning or the middle, but not the end of the
interactions indicated satisfactory observer accuracy. Coding results did not
differ between short and long video sequences, when sequences were taken from the
middle of the interactions. Importantly, characteristic differences between
different interactive situations were equally well represented in the short and
long video sequences. Therefore, our results show that coding only 10 min of an
interaction is as reliable and valid as coding full-length videos, if those short
sequences are taken from the middle of an interaction. Our findings support the
idea that for every method, it is necessary to individually determine the window
duration that is long enough to gain results that are reliable and valid.
PMID- 29937623
TI - Development of the Spence Children's Anxiety Scale - Short Version (SCAS-S).
AB - The literature provides several examples of anxiety symptoms questionnaires for
children. However, these questionnaires generally contain many items, and might
not be ideal for screening in large populations, or repeated testing in clinical
settings. The Spence Children's Anxiety Scale (SCAS) is an extensively used and
evaluated 44-item questionnaire developed to assess anxiety symptoms in children,
and provides a sound base for the development of an abbreviated anxiety symptoms
questionnaire. Although methodological standards have been presented in how to
develop abbreviated questionnaires, previous studies have often suffered from
several limitations regarding validating procedures. Guided by these
methodological standards, the current study aimed at developing an abbreviated
version of the SCAS, while retaining the content, convergent, and divergent
validity of the original scale. A school-based sample (n = 750) was used to
reduce the number of items, and an independent school-based sample (n = 371)
together with a clinical sample (n = 93), were used to validate the abbreviated
scale. The abbreviated version of the SCAS contained 19 items, it showed a clear
factor structure as evaluated in the independent sample, and it performed as good
as the original questionnaire regarding classification accuracy, convergent, and
divergent validity. In our view, the abbreviated version is a very good
alternative to the original scale especially for younger children, in initial
screening, or in order to reduce response burden.
PMID- 29937624
TI - The Psychometric Properties of an Internet-Administered Version of the Depression
Anxiety and Stress Scales (DASS) in a Sample of Dutch Adults.
AB - Psychometric work on the widely used Depression Anxiety and Stress Scales (DASS)
has mostly used classical psychometrics and ignored common internet-administered
versions. Therefore, the present study used not only classical, but also modern
psychometrics based on item response theory (IRT) to evaluate an internet
administered version of the DASS (Dutch translation). Internet-administered DASS
data were collected as part of a large internet-based study in the Dutch adult
population (n = 7972). Initially, external correlates (i.e. demographics other
measures) and some classical psychometrics (internal consistency,
convergent/divergent validity) of the DASS scales were evaluated. Next, IRT was
used to investigate the scales' dimensionality, discrimination and item
functioning. Finally, the DASS depression scale was further investigated by
linking it to the more clinically-oriented Quick Inventory of Depressive
Symptomatology (QIDS) using item response theory (IRT). Initial classical
psychometric analyses supported the scales' internal consistency (alpha = 0.94
0.98) and convergent/divergent validity. IRT analyses showed that each of the
DASS scales was only suitable to measure variations in a very narrow and rather
mild severity range. Linking the DASS depression scale with the QIDS also showed
that the DASS depression scale discriminated best in the mild-moderate severity
range, but not at higher severity levels that were covered by the QIDS. In
conclusion, the scales of the internet-administered DASS show good internal
consistency and validity. However, users should be aware that the scales
discriminate best at mild-moderate severity ranges in the general population.
PMID- 29937625
TI - Using a Videogame Intervention to Reduce Anxiety and Externalizing Problems among
Youths in Residential Care: an Initial Randomized Controlled Trial.
AB - Residential care is among the most intensive forms of treatment in youth care. It
serves youths with severe behavioral problems and is primarily focused on
targeting externalizing problems. Despite best efforts, effect sizes remain
moderate, which may be due to the disregarding of internalizing symptoms - in
particular anxiety - and to limitations regarding the delivery model of
interventions. This initial randomized controlled trial (n = 37) aimed to examine
the effectiveness of a biofeedback videogame intervention (Dojo) as an addition
to treatment as usual for youths with and without intellectual disability (ID) in
residential care with clinical levels of anxiety and externalizing problems. Dojo
targets both anxiety and externalizing problems, and incorporates the principles
of conventional treatment, while addressing its limitations. Youths were randomly
assigned to play Dojo (eight 30-min gameplay sessions) or to treatment as usual
(TAU). Measurements of anxiety and externalizing problems were conducted at
baseline, posttreatment, and 4-months follow-up through youths' self-report and
mentor-report. Completers-only analyses revealed decreases in self-reported
anxiety and externalizing problems, and mentor-reported anxiety at posttreatment
for participants in the Dojo condition compared to the control condition. Only
mentor-reported anxiety was maintained at follow-up. No effect was found for
mentor-reported externalizing problems. These findings provided preliminary
evidence that Dojo is a promising, innovative intervention that engages high-risk
youths. Practical implications are discussed.
PMID- 29937626
TI - The Role of External Inputs and Internal Cycling in Shaping the Global Ocean
Cobalt Distribution: Insights From the First Cobalt Biogeochemical Model.
AB - Cobalt is an important micronutrient for ocean microbes as it is present in
vitamin B12 and is a co-factor in various metalloenzymes that catalyze cellular
processes. Moreover, when seawater availability of cobalt is compared to
biological demands, cobalt emerges as being depleted in seawater, pointing to a
potentially important limiting role. To properly account for the potential
biological role for cobalt, there is therefore a need to understand the processes
driving the biogeochemical cycling of cobalt and, in particular, the balance
between external inputs and internal cycling. To do so, we developed the first
cobalt model within a state-of-the-art three-dimensional global ocean
biogeochemical model. Overall, our model does a good job in reproducing
measurements with a correlation coefficient of >0.7 in the surface and >0.5 at
depth. We find that continental margins are the dominant source of cobalt, with a
crucial role played by supply under low bottom-water oxygen conditions. The basin
scale distribution of cobalt supplied from margins is facilitated by the activity
of manganese-oxidizing bacteria being suppressed under low oxygen and low
temperatures, which extends the residence time of cobalt. Overall, we find a
residence time of 7 and 250 years in the upper 250 m and global ocean,
respectively. Importantly, we find that the dominant internal resupply process
switches from regeneration and recycling of particulate cobalt to dissolution of
scavenged cobalt between the upper ocean and the ocean interior. Our model
highlights key regions of the ocean where biological activity may be most
sensitive to cobalt availability.
PMID- 29937627
TI - Self-sustained actuation from heat dissipation in liquid crystal polymer
networks.
AB - Liquid crystal polymer networks (LCNs) lead the research geared toward
macroscopic motion of materials. These actuators are molecularly programed to
adapt their shape in response to external stimuli. Non-photo-responsive thin
films of LCNs covered with heat absorbers (e.g., graphene or ink) are shown to
continuously oscillate when exposed to light. The motion is governed by the heat
dissipated at the film surface and the anisotropic thermal deformation of the
network. The influence of the LC molecular alignment, the film thickness, and the
LC matrix on the macroscopic motion is analyzed to probe the limits of the
system. The insights gained from these experiments provide not only guidelines to
create actuators by photo-thermal or pure photo-effects but also a simple method
to generate mechanical oscillators for soft robotics and automated systems. (c)
2018 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published
by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1331
1336.
PMID- 29937628
TI - Social interaction effects: The impact of distributional preferences on risky
choices.
AB - This paper identifies convex distributional preferences as a possible cause for
the empirical observation that agents belonging to the same group tend to behave
similarly in risky environments. We first show theoretically that convex
distributional preferences imply social interaction effects in risky choices in
the sense that observing a peer choose a risky (safe) option increases the
agent's incentive to choose the risky (safe) option as well, even when lotteries
are stochastically independent and the agent can only observe the lottery chosen
by the peer but not the corresponding outcome. We then confirm our theoretical
predictions experimentally.
PMID- 29937629
TI - Large-scale heavy precipitation over central Europe and the role of atmospheric
cyclone track types.
AB - Precipitation patterns over Europe are largely controlled by atmospheric cyclones
embedded in the general circulation of the mid-latitudes. This study evaluates
the climatologic features of precipitation for selected regions in central Europe
with respect to cyclone track types for 1959-2015, focusing on large-scale heavy
precipitation. The analysis suggests that each of the cyclone track types is
connected to a specific pattern of the upper level atmospheric flow, usually
characterized by a major trough located over Europe. A dominant upper level cut
off low (COL) is found over Europe for strong continental (CON) and van Bebber's
type (Vb) cyclones which move from the east and southeast into central Europe.
Strong Vb cyclones revealed the longest residence times, mainly due to circular
propagation paths. The central European cyclone precipitation climate can largely
be explained by seasonal track-type frequency and cyclone intensity; however,
additional factors are needed to explain a secondary precipitation maximum in
early autumn. The occurrence of large precipitation totals for track events is
strongly related to the track type and the region, with the highest value of 45%
of all Vb cyclones connected to heavy precipitation in summer over the Czech
Republic and eastern Austria. In western Germany, Atlantic winter cyclones are
most relevant for heavy precipitation. The analysis of the top 50 precipitation
events revealed an outstanding heavy precipitation period from 2006 to 2011 in
the Czech Republic, but no gradual long-term change. The findings help better
understand spatio-temporal variability of heavy precipitation in the context of
floods and may be used for evaluating climate models.
PMID- 29937630
TI - Benefit transfer challenges: a U.S. Environmental Protection Agency perspective.
PMID- 29937631
TI - Is cloning horses ethical?
AB - This paper assesses whether cloning horses is ethical by reviewing ethical
arguments against cloning of nonequine species and determining whether they apply
to horses, analysing ethical arguments about horse cloning which do not apply to
noncompetitive species and considering the ethical dilemmas faced by
veterinarians involved in horse cloning. The author concludes that concerns about
the health and welfare of cloned horses render the technique ethically
problematic and that the onus is on those providing commercial equine cloning
services to collate data and provide a stronger evidence base for ethical
decision-making.
PMID- 29937632
TI - Implications of Environmental Chores for Schooling: Children's Time Fetching
Water and Firewood in Tanzania.
AB - In many developing countries, children devote substantial time to collecting
firewood and fetching water. Is there a connection between such time-consuming
work and children's schooling? If so, environmental degradation may have serious
detrimental implications for children's education. To explore this question, this
case study set in rural Tanzania uses evidence collected from children and their
mothers about children's environmental chores. Although the sample is small, we
find some descriptive quantitative evidence as well as qualitative evidence from
focus groups with children supporting such a link, consistent with results from
the few econometric analyses set in Africa. We also document substantial demands
by schools for students to fetch water. The proposed conceptual framework takes
into account confounding factors including school-related violence, which
affected more than one-third of children in this study. We make a case for future
research based on larger data collection projects designed to explore these
issues more fully.
PMID- 29937633
TI - What's New in Emergencies, Trauma, and Shock? Using Abdominal Computed Tomography
in Geriatric Patients on Warfarin.
PMID- 29937634
TI - Grace Under Pressure: Leadership in Emergency Medicine.
AB - Physicians in general, including emergency physicians (EPs), are trained in the
diagnostic, therapeutic, and administrative aspects of patient care but not so
much in the theoretical and practical aspects of assuming and delivery of
leadership. EPs are always taught to focus on their performance, to excel and
achieve, to be accountable for their own clinical decisions, and to appreciate
feedback and peer-to-peer review. Currently, if there are some semblances of
formal or semi-formal leadership instruction, the organized theoretical
curriculum often does not formally include very structured and planned
departmental leadership and management elements. Leadership is a process for a
person ("the leader") to lead, influence, and engage a group or organization to
accomplish their objectives and mission. To do this, the leader must understand a
variety of issues of working, interacting, and integrating with people, the
environment and both, the intrinsic and extrinsic factors, and elements that have
an impact on the industry or area he/she is leading in. Leadership in emergency
medicine (EM) is even more challenging, with its unique focus, issues, and
trajectory, moving into the new century, with new considerations. No single
strategy is sufficient to ace EM leadership and no single specific leadership
model is complete. This paper shares some current views on medical/EM leadership.
The author shares her views and some suggested proposals for more formal and
structured leadership, implementation, and succession to help nurture and groom
Eps who will become leaders in EM in the near future.
PMID- 29937636
TI - Utility of Abdominal Computed Tomography in Geriatric Patients on Warfarin with a
Fall from Standing.
AB - Context: Geriatric head trauma resulting from falls has been extensively studied
both in the presence and absence of blood thinners. In this population, however,
the prevalence and extent of abdominal injury resulting from falls are much less
defined. Aim: We aim to evaluate the utility of abdominal computed tomography
(CT) imaging in geriatric patients on Warfarin with a recent history of fall.
Setting and Design: A retrospective analysis was completed of consecutive
geriatric patients who presented to a Level 1 Trauma Center emergency department
after fall from standing while taking Warfarin. Methods: Inclusion criteria
included age 65 years or older and fall while taking Warfarin. Incomplete medical
records were excluded from the study. Data collection included the type of
anticoagulant medications, demographics, physical examination, laboratories, CT/X
ray findings if ordered, and final diagnosis on admission. Categorical variables
were examined using Pearson's Chi-square where appropriate (expected frequency
>5), or Fisher's Exact test. Continuous variables were examined using
nonparametric Wilcoxon rank tests. Results: Eight hundred and sixty-three charts
were reviewed. One hundred and thirty-one subjects met inclusion criteria. Mean
age was 83 years. Nearly 39.6% of patients were male. A total of 48 patients had
abdominal CT imaging. Seven of the 131 patients (5.3%) had an abdominal injury.
Abdominal tenderness was predictive of injury, with 4 of 7 cases with abdominal
injury demonstrating abdominal tenderness versus only 10 of 124 cases without
abdominal injury demonstrating tenderness (P = 0.003). Abdominal CTs were ordered
in 11 of 19 cases of patients that exhibited head trauma yet none of these
patients were shown to have sustained abdominal trauma (P = 0.08). There was no
association between international normalized ratio level and presence of
abdominal injury (P = 0.99). Conclusions: A small percentage of elderly fall
patients on Warfarin have a significant abdominal injury. Anticoagulated
geriatric patients are sometimes subjected to abdominal scans liberally without
supporting physical examination findings such as abdominal tenderness or presence
of a distracting injury. Specifically, the utility of abdominal CT is
questionable in isolated head injury patients. Further, taking Warfarin or other
anticoagulant medications do not seem to increase the risk of intraabdominal
injury.
PMID- 29937635
TI - Guiding Management in Severe Trauma: Reviewing Factors Predicting Outcome in
Vastly Injured Patients.
AB - Trauma is one of the leading causes of death worldwide, with road traffic
collisions, suicides, and homicides accounting for the majority of injury-related
deaths. Since trauma mainly affects young age groups, it is recognized as a
serious social and economic threat, as annually, almost 16,000 posttrauma
individuals are expected to lose their lives and many more to end up disabled.
The purpose of this research is to summarize current knowledge on factors
predicting outcome - specifically mortality risk - in severely injured patients.
Development of this review was mainly based on the systematic search of PubMed
medical library, Cochrane database, and advanced trauma life support Guiding
Manuals. The research was based on publications between 1994 and 2016. Although
hypovolemic, obstructive, cardiogenic, and septic shock can all be seen in multi
trauma patients, hemorrhage-induced shock is by far the most common cause of
shock. In this review, we summarize current knowledge on factors predicting
outcome - more specifically mortality risk - in severely injured patients. The
main mortality-predicting factors in trauma patients are those associated with
basic human physiology and tissue perfusion status, coagulation adequacy, and
resuscitation requirements. On the contrary, advanced age and the presence of
comorbidities predispose patients to a poor outcome because of the loss of
physiological reserves. Trauma resuscitation teams considering mortality
prediction factors can not only guide resuscitation but also identify patients
with high mortality risk who were previously considered less severely injured.
PMID- 29937637
TI - Integration of Point-of-care Ultrasound during Rapid Sequence Intubation in
Trauma Resuscitation.
AB - Introduction: Airway and breathing management play critical role in trauma
resuscitation. Early identification of esophageal intubation and detection of
fatal events is critical. Authors studied the utility of integration of point-of
care ultrasound (POCUS) during different phases of rapid sequence intubation
(RSI) in trauma resuscitation. Methods: It was prospective, randomized single
centered study conducted at the Emergency Department of a level one trauma
center. Patients were divided into ultrasonography (USG) and clinical examination
(CE) arm. The objectives were to study the utility of POCUS in endotracheal tube
placement and confirmations and identification of potentially fatal conditions as
tracheal injury, midline vessels, paratracheal hematoma, vocal cord pathology,
pneumothorax, and others during RSI. Patient >1 year of age were included. Time
taken for procedure, number of incorrect intubations, and pathologies detected
were noted. The data were collected in Microsoft Excel spread sheets and analyzed
using Stata (version 11.2, Stata Corp, Texas, U. S. A) software. Results: One
hundred and six patients were recruited. The mean time for primary survey USG
versus CE arm was (20 +/- 10.01 vs. 18 +/- 11.03) seconds. USG detected four
pneumothorax, one tracheal injury, and one paratracheal hematoma. The mean
procedure time USG versus CE arm was (37.3 +/- 21.92 vs. 58 +/- 32.04) seconds.
Eight esophageal intubations were identified in USG arm by POCUS and two in CE
arm by EtCO2 values. Conclusion: Integration of POCUS was useful in all three
phases of RSI. It identified paratracheal hematoma, tracheal injury, and
pneumothorax. It also identified esophageal intubation and confirmed main stem
tracheal intubation in less time compared to five-point auscultation and
capnography.
PMID- 29937638
TI - A Pilot Study of Viscoelastic Monitoring in Pediatric Trauma: Outcomes and
Lessons Learned.
AB - Background: Examine the characteristics and outcomes of pediatric trauma patients
at risk for coagulopathy following implementation of viscoelastic monitoring.
Materials and Methods: Injured children, aged <18 years, from September 7, 2014,
to December 21, 2015, at risk for trauma-induced coagulopathy were identified
from a single, level-1 American College of Surgeons verified pediatric trauma
center. Patients were grouped by coagulation assessment: no assessment (NA),
conventional coagulation testing alone (CCT), and conventional coagulation
testing with rapid thromboelastography (rTEG). Coagulation assessment was
provider preference with all monitoring options continuously available. Groups
were compared and outcomes were evaluated including blood product utilization,
Intensive Care Unit (ICU) utilization, duration of mechanical ventilation, and
mortality. Results: A total of 155 patients were identified (NA = 78, CCT = 54,
and rTEG = 23). There was no difference in age, gender, race, or mechanism. In
practice, rTEG patients were more severely injured, more anemic, and received
more blood products and crystalloid (P < 0.001). rTEG patients also had increased
mortality with fewer ventilator and ICU-free days. Multivariate logistic
regression and covariance analysis indicated that while rTEG use was not
associated with mortality, it was associated with increased use of blood
products, duration of mechanical ventilation, and ICU length of stay.
Conclusions: Viscoelastic monitoring was infrequently performed, but utilized in
more severely injured patients. Well-designed prospective studies in patients at
high risk of coagulopathy are needed to evaluate goal-directed hemostatic
resuscitation strategies in children.
PMID- 29937639
TI - Validation of Predicting Hyperglycemic Crisis Death Score: A Risk Stratification
Tool for Appropriate Disposition of Hyperglycemic Crisis Patients from the
Emergency Department.
AB - Context: Predicting hyperglycemic crisis death (PHD) score is a simple, rapid
tool with six independent mortality predictors to calculate 30-day mortality and
appropriately dispose patients to Intensive Care Unit (ICU) or ward. Aims: This
study aimed at validating the efficiency of PHD score as a decision rule for
prognosticating 30-day mortality and classifying hyperglycemic crisis patients
for appropriate disposition from the emergency department (ED). Materials and
Methods: This is a prospective, observational study done in the ED of a teaching
hospital over 14 months. All patients aged >18 years and who met the criteria of
hyperglycemic crisis were enrolled. Thirty-day mortality of six independent
predictors was the primary end point. Using PHD, risk scores were calculated and
patients were disposed as per physician's clinical judgment. Finally, the
treating physician's decision and PHD score disposition were compared and the
efficiency of PHD in predicting 30-day mortality was analyzed. Multiple logistic
regression models were used for analysis. Receiver operating characteristic curve
was drawn, and area under the curve along with sensitivity, specificity, positive
predictive value, and negative predictive value was analyzed. P < 0.05 was
considered statistically significant. Results: A total of 133 patients were
included. On applying PHD score, 69, 39, and 25 patients were in the low-,
intermediate-, and high-risk groups, respectively, with a mortality rate of 5.8%,
20.5%, and 56%, respectively. On comparing physician disposition with PHD score,
an increasing mortality was noticed in ICU, and PHD showed equal weight in risk
stratification and appropriate disposition of patients. Conclusion: In adult
patients with hyperglycemic crisis, PHD score is validated as a straightforward,
prompt tool for predicting 30-day mortality and aids in disposition. The
mortality rate in the PHD score Model II was similar to the physician's clinical
decision.
PMID- 29937640
TI - Validation of the Cincinnati Prehospital Stroke Scale.
AB - Background: Early recognition of Stroke is one of the key concepts in the "Chain
of Survival" as described by the American Heart Association/American Stroke
Association Stroke guidelines. The most commonly used tools for prehospital
assessment of stroke are "The Cincinnati Prehospital Stroke Scale," (CPSS) the
"Face, Arm, Speech Test," and "The Los Angeles Prehospital Stroke Screen." The
former two are used to identify stroke using physical findings while the latter
is used to rule out other causes of altered consciousness. Aim: The aim of this
study is to validate the CPSS in the prehospital setting by correlating with
computed tomography scan findings. (1) To determine if these scores can be
implemented in the Indian prehospital setting. (2) To determine if it is feasible
for new emergency departments (EDs) to use these protocols for early detection of
stroke. Methodology: A prospective, observational study from December, 2015 to
March, 2016. Patients with suspected stroke were enrolled. Data were collected
prehospital in patients that arrived to the ED in an ambulance. Sensitivity,
specificity, positive predictive value, and negative predictive value of the
score were calculated using standard formulae. Results: CPSS showed good
sensitivity of 81% (confidence interval [CI] - 68.5%-97%) when combined and a
positive predictive value (PPV) of 100% (CI: 91.9%-100%). Individually, they
showed a sensitivity of 75.8%, 79%, and 74.1%, respectively, with a PPV of 100%
and specificity of 95%-100%. Conclusion: As a prehospital screening tool, CPSS
can be extremely useful as any diagnosis is only provisional until confirmed by
an appropriate investigation in a hospital.
PMID- 29937641
TI - Comparison of Ultrasound and Plain Radiography for the Detection of Long-bone
Fractures.
AB - Objective: To compare emergency medicine (EM) resident physicians' ability to
identify long-bone fractures using ultrasound (US) versus plain radiography (X
ray). Methods: This was an IRB-approved, randomized prospective study. Study
participants included 40 EM residents at a single site. Fractures were
mechanically induced in five chicken legs, and five legs were left unfractured.
Chicken legs were imaged by both modalities. Participants were given 2 min to
view each of the images. Participants were randomized to either US or X-ray
interpretation first and randomized to viewing order within each arm.
Participants documented the presence or absence of fracture and location and type
of fracture when pertinent. Mean proportions and standard deviations (SDs) were
analyzed using paired t-test and linear models. Results: Forty residents (15
postgraduate years (PGY)-1, 12 PGY-2, 13 PGY-3) participated in the study. Thirty
one participants were male, and 19 were randomized to US first. Residents
completed a mean of 185 (SD 95.8) US scans before the study in a variety of
applications. Accurate fracture identification had a higher mean proportion in
the US arm than the X-ray arm, 0.89 (SD 0.11) versus 0.75 (SD 0.11), respectively
(P < 0.001). There was no statistically significant difference in US arm and X
ray arm for endpoints of fracture location and type. Conclusion: EM residents
were better able to identify fractures using US compared to X-ray, especially as
level of US and ED experience increased. These results encourage the use of US
for the assessment of isolated extremity injury, particularly when the injury is
diaphyseal.
PMID- 29937642
TI - Snakebites in Lebanon: A Descriptive Study of Snakebite Victims Treated at a
Tertiary Care Center in Beirut, Lebanon.
AB - Background: Snakebites lead to at least 421,000 envenomations and result in more
than 20,000 deaths per year worldwide. Few reports exist in the Mediterranean
region. This study describes demographic and clinical characteristics, treatment
modalities, and outcomes of snakebites in Lebanon. Materials and Methods: This
was a retrospective chart review of patients who presented with snakebite
complaint to the emergency department between January 2000 and September 2014.
Results: A total of 24 patients were included in this study. The mean age was
34.6 (+/-16.4) years and 58.3% were males. Local manifestations were documented
in 15 (62.5%) patients, systemic effects in 10 (41.7%), hematologic abnormalities
in 10 (41.7%), and neurologic effects in 4 (16.7%) patients. Nine patients
(37.5%) received antivenom. The median amount of antivenom administered was 40 ml
or 4 vials (range: 1-8 vials). About 50% of patients were admitted to the
hospital with 75% to an Intensive Care Unit and 25% to a regular bed. All were
discharged home with a median hospital length of stay of 4 (interquartile range
11) days. Among those admitted, seven patients (58.3%) had at least one
documented complication (compartment syndrome, fasciotomy, intubation, deep vein
thrombosis, coagulopathy, acute respiratory distress syndrome, sepsis, congestive
heart failure, cellulitis, upper gastrointestinal bleeding, and vaginal
bleeding). Conclusion: Victims of snakebites in Lebanon developed local,
systemic, hematologic, or neurologic manifestations. Complications from
snakebites were frequent despite antivenom administration. Larger studies are
needed to assess the efficacy of available antivenom and to possibly create a
local antivenom for the treatment of snakebites in Lebanon.
PMID- 29937643
TI - Bedside Lung Ultrasound in Emergency Protocol as a Diagnostic Tool in Patients of
Acute Respiratory Distress Presenting to Emergency Department.
AB - Objective: The objective of this study is to determine the accuracy of the
bedside lung ultrasound in emergency (BLUE) protocol in giving a correct
diagnosis in patients presenting with acute respiratory distress in emergency
department. Materials and Methods: Patients with acute respiratory distress were
evaluated. Ultrasound findings such as artifacts (A line, B line), lung sliding,
alveolar consolidation or pleural effusion, and venous analysis were recorded.
Ultrasonography findings were correlated with final diagnosis made by the
treating unit. Sensitivity and specificity were calculated. Results: A total 50
patients were evaluated. The A profile (predominant A line with lung sliding)
indicated chronic obstructive pulmonary disease/asthma (n = 14) with 85.17%
sensitivity and 88.88% specificity. B profile (predominant B + lines with lung
sliding) indicated pulmonary edema (n = 13) with 92.30% sensitivity and 100%
specificity. The A/B profile (A line on one side and B + line on other side) and
the C profile (anterior consolidation) and the A profile plus posterolateral
alveolar and/or pleural syndrome indicated pneumonia (n = 17) with 94.11
sensitivity and 93.93% specificity. The A profile plus venous thrombosis
indicated pulmonary embolism (n = 1) with 100% sensitivity and specificity. A'
profile (predominant A line without lung sliding) with lung point indicated
pneumothorax (n = 5) with 80% sensitivity and 100% specificity. Conclusion: BLUE
protocol was successful in average 90.316% cases. BLUE performed in emergency
department is equivalent to computed tomography scan. BLUE protocol aids in
making diagnosis and saves time and cost; avoids the side effects related to
radiation.
PMID- 29937644
TI - True Costs of Medical Clearance: Accuracy and Disagreement between Psychiatry and
Emergency Medicine Providers.
AB - Introduction: Medical clearance is required to label patients with mental illness
as free of acute medical concerns. However, tests may extend emergency department
lengths of stay and increase costs to patients and hospitals. The objective of
this study was to determine how knowledgeable emergency and psychiatric providers
are about the costs of tests used for medical clearance. Materials and Methods:
We surveyed the department of psychiatry (Psych) and department of emergency
medicine (EM) faculty and residents to obtain their estimates of the costs of 18
laboratory/imaging studies commonly used for medical clearance. Survey responses
were analyzed using the Wilcoxon signed-rank test to compare the median cost
estimates between residents and faculty in EM and Psych. Results: A total of 99
physicians (response rate, 47.8%) completed the survey, including 47 faculty (EM
= 28; Psych = 20) and 52 residents (EM = 29; Psych = 23). Across all the groups,
cost estimates for tests were inaccurate, off by several hundred dollars for
three tests, and by $13-$80 for 15. Significant differences between EM and Psych
providers for estimated median costs of specific tests included between residents
for urine drug screens (EM: $800; Psych: $50; P < 0.0001) and ECG (EM: $25;
Psych: $75; P = 0.004); between faculty for urinalysis (EM: $40; Psych: $18; P =
0.020) and urine drug screen (EM: $100; Psych: $10; P < 0.0001); and between all
physicians for urine drug screen (EM: $500; Psych: $50; P < 0.0001). Conclusion:
Further education on the financial costs of medical clearance is needed to inform
workup decisions and consensus between emergency and psychiatric providers.
PMID- 29937645
TI - Measurement of a Novel Biomarker, Secretory Phospholipase A2 Group IIA as a
Marker of Sepsis: A Pilot Study.
AB - Introduction: Early identification of sepsis is critical as early treatment
improves outcomes. We sought to identify threshold values of secretory
phospholipase A2 (sPLA2)-IIA that predict sepsis and bacterial infection compared
to nonseptic controls in an emergency department (ED) population. Materials and
Methods: This is a prospective cohort of consenting adult patients who met two or
more systemic inflammatory response syndrome (SIRS) criteria with clinical
diagnosis of infectious source likely (septic patients). Controls were nonseptic
consenting adults undergoing blood draw for other ED indications. Both groups had
blood drawn, blind-coded, and sent to an outside laboratory for quantitative
analysis of sPLA2-IIA levels. The study investigators reviewed patients'
inpatient medical record for laboratory, imaging, and microbiology results, as
well as clinical course. Results: sPLA2-IIA levels were significantly lower in
control patients as compared to septic patients (median = 0 ng/ml [interquartile
range (IQR): 0-6.5] versus median = 123 ng/ml [IQR 44-507.75]; P < 0.0001). SPLA2
IIA levels were higher in patients with confirmed source (n = 28 patients, median
= 186 ng/ml, 95% confidence interval = 115.1-516.8) as compared to those with no
source identified or a viral source (n = 17, median = 68 ng/ml, 95% confidence
interval = 38.1-122.7; P = 0.04). Using a cutoff value of 25 ng/ml, sPLA2-IIA had
a sensitivity of 86.7% (confidence interval 72.5-94.5) and a specificity of 91.1%
(confidence interval 77.9-97.1) in detecting sepsis. Conclusions: sPLA2-IIA shows
potential as a biomarker distinguishing sepsis from other disease entities.
Further study is warranted to identify predictive value of trends in sPLA-IIA
during disease course in septic patients.
PMID- 29937646
TI - Amitraz Poisoning: The (Un) Common Poisoning.
AB - Pesticide poisoning is always a clinical conundrum for the emergency physician
(EP), the complexity of which increases when the pesticide has no antidote! Over
the past decade, there has been a sharp increase in cases of Amitraz poisoning, a
pesticide routinely used in veterinary medicine, available without a
prescription. The usual presentation includes bradycardia, hypotension, poor
sensorium, and miosis. In the absence of accurate history, these clinical
features can be confused with the cholinergic toxidrome of organophosphorus
poisoning. There is a dearth of literature regarding the presentation and
protocols for the management of Amitraz poisoning with data mostly based on
animal studies and pediatric case reports. Currently, the available medical
literature in the form of case reports and case series form an invaluable source
of information to the EP to formulate a working diagnosis and methodical approach
to this pesticide. Here, we present two case reports highlighting the
characteristic clinical features and bringing to light how an organized approach
to the toxin can give satisfactory results.
PMID- 29937647
TI - Acute Appendicitis as an Unexpected Cause of Inverted Takotsubo Cardiomyopathy.
AB - Takotsubo cardiomyopathy (TTC), also known as transient left ventricular
ballooning syndrome, is a stress-induced-cardiomyopathy. It is precipitated by
emotional or physical stress and is characterized by normal coronary arteries and
transient regional wall motion abnormalities. Variants of TTC include apical
ballooning syndrome and, less commonly, mid, basal, and local variants. New onset
heart failure or acute coronary syndromes are a common presentation of TTC.
Arrhythmias such as VT, VF, and torsade de pointes have also been reported. We
present here a 42-year-old man with an inverted Takotsubo variant with pulmonary
edema and transient accelerated idioventricular rhythm. He was initially admitted
in the Emergency Department for acute and non-complicated appendicitis. Coronary
angiogram showed normal coronary arteries and left ventriculography revealed a
reverse variant of TTC. The patient had completely recovered. Myocarditis was
ruled out by cardiac magnetic resonance imaging.
PMID- 29937648
TI - Inferior Vena Cava Obstruction and Shock.
AB - Shock is one of the most challenging life-threatening conditions with high
mortality and morbidity; the outcomes are highly dependent on the early detection
and management of the condition. Septic shock is the most common type of shock in
the Intensive Care Unit. While not as common as other subsets of shock,
obstructive shock is a significant subtype due to well defined mechanical and
pathological causes, including tension pneumothorax, massive pulmonary embolism,
and cardiac tamponade. We are presenting a patient with obstructive shock due to
inferior vena cava obstruction secondary to extensive deep venous thrombosis.
Chance of survival from obstructive shock in our patient was small; however,
there was complete and immediate recovery after treatment of the obstruction on
recognizing the affected vessels. This case alerts the practicing intensivist and
the emergency medicine physician to consider occlusion of the great vessels other
than the pulmonary artery or aorta as causes of obstructive shock.
PMID- 29937649
TI - Concomitance Acute Cerebral Infarction and Remote Intra-Cerebral Hemorrhaging on
Arrival.
PMID- 29937651
TI - Platelet-rich fibrin: Emerging biomaterial in regeneration.
PMID- 29937650
TI - Mild Traumatic Brain Injury Associated with Internal Carotid Artery Dissection
and Pseudoaneurysm.
PMID- 29937652
TI - Literature review of 86 cases of mandibular ameloblastic carcinoma.
AB - Ameloblastic carcinoma is considered to be a rare epithelial malignant neoplasm
of odontogenic origin occurring mainly in the mandible. Ameloblastic carcinoma
has been a topic of controversy regarding management from past many years. We
reviewed 86 cases of mandibular ameloblastic carcinoma from 1981 to 2014, on the
basis of the electronic search of peer-reviewed journals in MEDLINE (PubMed)
database. Age, sex, tumor size, treatment delivered, recurrence, metastasis,
follow-up period, and dead/alive status are tabulated, and the data are analyzed.
The mean age was 43.47 years with standard deviation +/- 21.09. The age range was
between 15 and 91 years, and male to female ratio was 2.18:1. Knowledge gained
from the present review would help in establishing the best therapeutic options
for ameloblastic carcinoma, and it also encourages the further reporting of
ameloblastic carcinoma.
PMID- 29937653
TI - Correlation of CD133 and Oct-4 expression with clinicopathological and
demographic parameters in oral squamous cell carcinoma patients.
AB - Objective: Squamous cell carcinoma of oral cavity is one of the most common
cancers of Indian subcontinent with the 5-year survival rate of 50% despite the
recent advances in the treatment. The aim of the present study was to study
cancer stem cell markers CD133 and Oct-4 in oral squamous cell carcinoma (OSCC)
patients and their correlation with clinicopathological variables. Materials and
Methods: This was a prospective study which included 50 cases of
histopathologically proven squamous cell carcinoma of oral cavity. Expression of
CD133 and Oct-4 was evaluated by immunohistochemistry (IHC) and their expression
was correlated with various clinicopathological and demographic parameters.
Results: CD133 expression was seen in 20.6% cases of clinical Stage I-II and in
79.4% of clinical stage of III-IV OSCC patients, the difference being
statistically significant with the P = 0.048. There was no statistically
significant association between CD133 expression and any other
clinicopathological or demographic variable. Oct-4 was expressed only in one
case. Conclusions: CD133 expression was significantly seen higher in Stage III-IV
tumors, the stem cells may be responsible for the aggressiveness of the OSCCs and
these stem cells can be potential prognostic markers and targets for the future
targeted therapy.
PMID- 29937654
TI - Probing natural substitute for formalin: Comparing honey, sugar, and jaggery
syrup as fixatives.
AB - Background: Since its discovery in 1859, formalin has been considered as the
"gold standard" in tissue fixation. As formalin is highly toxic and carcinogenic,
the quest for its substitute has started recently. Literature search reveals very
sparse studies on natural substitute for formalin. Here, it is an attempt to
explore eco-friendly, economical, and readily available natural substance for
formalin substitute. Aim: The aim of our study was to evaluate the efficacy of
natural fixatives such as honey, sugar, jaggery, and water in comparison to the
standard fixative used like formalin. Materials and Methods: Fresh goat tissues
(tongue) were fixed separately with buffered 10% formalin (positive control),
honey, sugar syrup, jaggery syrup, and distilled water (negative control). 24 h
fixation was done at room temperature followed by conventional processing and
routine H and E staining. The stained sections were assessed for cytoplasmic and
nuclear detail by three pathologists under light microscope and were graded
accordingly. Results: The results showed statistically significant differences
between jaggery with other natural fixatives for both nuclear details and
cytoplasmic staining. Conclusion: The preservation of tissue by honey, sugar, and
jaggery syrup was comparable to that of formalin. Among the three natural
fixatives, jaggery syrup excelled. Hence, it can be considered as an equally
effective formalin substitute.
PMID- 29937655
TI - A randomized controlled clinical trial evaluating the efficacy of zoledronate gel
as a local drug delivery system in the treatment of chronic periodontitis: A
clinical and radiological correlation.
AB - Background: This study aimed to evaluate the efficacy of local drug delivery
system of zoledronate (ZLN) gel as an adjunct to scaling and root planing (SRP)
for the treatment of human periodontal intrabony defects clinically and
radiographically. Materials and Methods: Forty intrabony defects (three walled
and combined defects without involving furcation) in moderate to severely
affected forty chronic periodontitis patients (range, 30-50 years) were randomly
divided into two groups and treated either with 0.05% ZLN gel (ZLN n = 20; 1
dropout) or placebo gel (control group [CG] n = 20) after SRP. Clinical
parameters such as plaque index (PI), gingival index (GI), tooth-specific pocket
probing depth (Ts PPD), and clinical attachment levels (TsCAL) were assessed at
baseline and at 3 and 6 months using occlusal acrylic stent. Radiographic
parameters were assessed at baseline and 6 months, utilizing "ONIS 2.5
PROFESSIONAL" and "SYNGO" software compatible with DentaScan to measure the
volumetric bone changes in intrabony defects. Results: In intragroup comparisons,
both groups showed significant PI and GI reduction (P < 0.001) after treatment at
3 and 6 months. In intergroup comparisons, Ts PPD reduction and Ts CAL gain were
significant only in ZLN at 6 months from both baseline and 3 months.
Radiographically, significant reduction in defect depth and buccolingual width
with volumetric defect gain of 40.24% +/- 7.44% in ZLN compared to insignificant
gain of 1.60% +/- 4.06% in CG was observed at 6 months. Conclusion: ZLN gel
applied subgingivally in intrabony defects resulted in significant improvements
both clinically and radiographically.
PMID- 29937656
TI - Erich arch bar versus hanger plate technique for intermaxillary fixation in
fracture mandible: A prospective comparative study.
AB - Introduction: Various methods have been described for intermaxillary fixation
(IMF) for treatment of faciomaxillary injuries. Many studies have been described
to evaluate the efficacy of different methods. Hanger plate method has not been
commonly used. The aim of the present study was to compare the advantages and
disadvantages of this method over Erich arch bar in mandibular fracture.
Materials and Methods: Sixty patients of only mandibular fracture presenting to
trauma center requiring open reduction and internal fixation under general
anesthesia were randomly allocated to Group A and Group B comprising thirty
patients in each. Group A included patients who received IMF with Erich arch bar.
Group B included patients who received IMF with hanger plate method. The two
groups were compared for time duration of intermaxillary procedure, total
duration of surgery, oral hygiene score, postoperative occlusion, and
complications. Results: The average time of intermaxillary procedure, total
duration of surgery, and wire prick injuries were more in Group A. Oral hygiene
score was significantly better in Group B. Postoperative occlusion was comparable
between the two groups. There was screw loosening in four patients in Group B,
but none had tooth root injury. The cost of material for IMF was more in Group B.
Conclusion: IMF with hanger plate method is more safe and efficacious compared to
Erich arch bar in the treatment of mandibular fractures.
PMID- 29937657
TI - Immediately placed dental implants in smokers with plasma rich in growth factor
versus without plasma rich in growth factor: A comparison.
AB - Introduction: The placement of implants into fresh extraction sockets was
introduced in 1970. This approach has been reviewed extensively during the past
decade. Immediate postextraction implant placement is a well-accepted protocol.
The concept of placement of dental implants soon after the removal of a tooth in
smokers, however, is still a matter of controversy. Purpose: (i) To access
failure rate of dental implant in smokers (ii) To evaluate added advantage of
plasma rich in growth factors (PRGFs) in immediate placement of dental implants
in smokers. Materials and Methods: The sample of 30 patients was obtained from
the different Outpatient Department of Faculty of Dental Sciences; King George's
Medical University, Lucknow, who had visited for rehabilitation of missing teeth
by implants between April 2013 and July 2015. They were randomly divided into two
groups (without use of PRGF and with use of PRGF) of 15 each. Pre- and
postoperative assessment included a thorough history and clinical examination,
regression of pain and swelling, implant stability by resonance frequency
analysis (RFA), and implant stability according to the bone type as well as
radiographic interpretation for measurement of bone loss on the mesial and distal
surfaces of the implant. Results: In this study, pain and swelling were
significantly (P < 0.05) higher in Group A than in Group B across the time
interval. RFA score for implant stability was lower in Group A across the period
than Group B. At the end of 3 months, RFA score (mean) in Group A was having
72.55 ISQ value, and in Group B, it was 75.71 ISQ value. In this study,
postoperative crestal bone loss was more in patients in Group A as compared to
patients in Group B. There was significant difference in mesial (P = 0.003) and
distal (P = 0.001) crestal bone loss at 6 months between the groups. Conclusion:
The immediate placement of dental implants in smokers with use of PRGF is shown
to be efficient in relation to postoperative pain and swelling, stability,
stability according to bone type, as well as bone loss.
PMID- 29937658
TI - The maxillofacial injuries: A postmortem study.
AB - Objectives: The aim of our study is to evaluate the incidence and etiology of
maxillofacial fractures in autopsy cases of KGMU, Lucknow. Materials and Methods:
The sample consisted of 444 autopsy cases with maxillofacial injuries, who were
brought to the mortuary of KGMU, Lucknow, for postmortem in the last year.
Parameters such as gender, age, cause, type, and site of injury are evaluated.
Result: The results of this study show that road traffic accidents are the main
reason for maxillofacial injuries in the deceased, followed by railway accidents.
Maxillofacial injuries are more common in adult males than in females. Majority
cases also involved maxilla and zygomatic along with mandible. The most common
type of facial fracture was Le Fort-2 fracture. Conclusion: Maxillofacial
injuries are commonly seen in adult males, due to RTA, involving maxilla,
zygomatic and mandible and presenting as Le Fort-2 fracture.
PMID- 29937659
TI - A comparative evaluation of the antimicrobial efficacy of calcium hydroxide,
chlorhexidine gel, and a curcumin-based formulation against Enterococcus
faecalis.
AB - Aim: This study aimed for a comparative evaluation of the antimicrobial efficacy
of calcium hydroxide, chlorhexidine gel, and a curcumin-based formulation against
Enterococcus faecalis. Methods: Thirty single-rooted teeth were taken. Access
preparation was done. Biomechanical preparation was done using Protaper universal
file till F3. Teeth were decoronated to a standardized root length of 14 mm, and
the apical end from outside was sealed using paraffin wax. Teeth were autoclaved
under standard conditions and after autoclaving, Phosphate-buffered saline
solution was introduced into the roots and was incubated for 24 h to check for
the disinfection of roots. Once the disinfection of roots was achieved, the wild
strain of E. faecalis, i.e., ATC 29212 strain, was introduced into the teeth and
allowed to incubate for 24 h. Following bacterial colonization inside the roots,
antimicrobials were introduced and efficacy was checked. The data obtained were
subjected to statistical analysis using paired t-test for significance. Results:
Significant difference was observed between all the test groups. However,
chlorhexidine gel showed the best value of mean difference, indicating it as the
best antibacterial medicament. Conclusion: Within the limitations of this study,
it can be concluded that chlorhexidine gel showed better antimicrobial properties
against E. faecalis than other medicaments.
PMID- 29937661
TI - Salivary hamartoma with a bifid tongue in an adult patient.
AB - Congenital anomalies of tongue are rare disorders usually associated with
syndromes. In present article we describe a case of a non-syndromic adult patient
with bifid tongue with salivary hamartoma on the dorsum of the tongue. We
described the clinical features, problems faced by the patient and management. As
etiology is uncertain we should have proper understanding of embryology.
PMID- 29937660
TI - Oral squamous cell carcinoma profile in North-Eastern regions of India from
habits to histopathology: A hospital-based study.
AB - Background: Head and neck cancers constitute about 5%-8% of total body cancers in
Europe, America, but in India, this figure is somewhat higher. The aim of this
study is to evaluate the current burden of oral cancers in India, particularly
North-East India. Materials and Methods: A full-length study starting from
patient counseling to clinical and histopathological examination and grading was
planned. The study was conducted under the guidance of clinician, oral surgeon,
oral pathologists, and statistician. Results: In the 3 years study, all the
patients with oral lesions are examined clinically, out of them suspected oral
cancer patients were histopathologically confirmed as oral squamous cell
carcinoma patient. The socioeconomic profile of oral cancer patients in relation
to all examined patients was summarized, and results are drawn. Conclusion: The
studied population is heavily indulgent tobacco consumption. Education for cancer
prevention, early detection, and treatment is needed.
PMID- 29937662
TI - Basaloid squamous cell carcinoma - A rare and aggressive variant of squamous cell
carcinoma: A case report and review of literature.
AB - Basaloid squamous cell carcinoma (BSCC) is a rare and aggressive variant of oral
squamous cell carcinoma with a predilection for the tongue and in other
locations, such as floor of the mouth, palate, retromolar trigone, and gingival
mucosa. Here, we present a case of BSCC of oropharynx in a 60-year-old male
patient.
PMID- 29937663
TI - A case of cleft lip and palate with severe maxillary retrognathism treated by
distraction osteogenesis and custom made intraoral rapid maxillary expansion
appliance: A 2-year follow-up of retention.
AB - Herewith, a case is reported of an adolescent female patient with maxillary
retrognathism due to restricted growth arising out of the previous cheiloplasty
and palatoplasty surgeries treated for cleft lip and palate. She also presented
an oroantral fistula in the scarred tissues of the palatal region. There was
anterior crossbite and distorted occlusion in the anterior segment with crowding
and open bite. There is maxillomandibular discrepancy of 6 degrees degrees . The
distraction osteogenesis was performed so as treat the maxillary hypoplasia. This
allows undermanding adaptation of the soft-tissue structures to the modification
in the skeletal structures as a result of surgical procedures and ensures long
term stability. A custom made intraoral rapid maxillary expansion device was
prepared utilizing the hyrax screw for the distraction of the bony segments. At
the end of the treatment and a retention period of 24 months, the patient
exhibited improved facial profile and hence esthetics.
PMID- 29937664
TI - Traumatic pseudoaneurysm of the superficial temporal artery.
AB - Aneurysms of the facial vasculature due to various accidental, violent, and
surgical injuries have been reported since mid-17th century. Approximately 386
pseudoaneurysms of the superficial temporal artery (STA) have been reported in
the literature since 1644. Traumatic pseudoaneurysm of the STA is a rare lesion.
It manifests as a painless pulsatile mass in the temporal region following
trauma. The unusual incidence and confusing presentation require the clinicians
to have a thorough knowledge of its presentation and diagnosis. We present a case
of traumatic pseudoaneurysm of the STA, which developed a few weeks later, after
sustaining blunt trauma to the head. We have also reviewed the anatomical
challenges and pathophysiology that promotes the formation of pseudoaneurysm and
the optimal approach to diagnose and manage the lesion. Pulsatile lesions or
lesions that are continuous with the STA should be regarded with extreme caution.
The sole treatment modality is surgical resection of the pseudoaneurysm. This
will avoid any future complications such as hemorrhage or compression of adjacent
nerves and vessels.
PMID- 29937665
TI - Efficacious use of a Calgigraf Ag foam dressing in complete healing of a
difficult-to-heal, long-standing ulcer of osteoradionecrosis.
AB - A number of dressings containing silver have been recently introduced into the
wound care market as increased resistance to antibiotics has become a problem in
treating infected wounds. A 54-year-old male, with adenoid cystic carcinoma
treated by segmental resection and reconstruction of mandible using
reconstruction plate with concomitant radiotherapy, resulted in a deep extraoral
nonhealing necrotic, exuding, malodorous, and painful wound. Erythema, eczema,
and trophic changes were surrounding the skin. Previous treatment was removal of
exposed reconstruction plate and primary closure. Culture samples reported
methicillin-resistant Staphylococcus aureus positive and sensitivity to
linezolid. Repeated failed attempts to approximate the wound, prompted the use of
Calgigraf Ag foam as dressing for the wound. Evidence of new tissue growth and
subsequent reduction in wound area and exudate were significant. Chronic
nonhealing wounds involving progressive tissue loss give rise to the biggest
challenge to wound-care researchers. Despite proper care, some wounds fail to
heal in normally and become chronic. The use of ionic silver with negative
pressure therapy is safe and effective in difficult nonhealing wounds. This case
illustrates the potential benefit of ionic silver combined with negative pressure
and moist wound healing as management of a patient with long-standing,
nonhealing, and osteoradionecrosis wound. Calgigraf Ag Foam a silver alginate
dressing is optimal for maintaining moist environment vital to promote wound
healing. It needs less frequent dressing changes with additional benefits such
management of excessive exudate minimising malodour and maintaining a moist wound
environment.
PMID- 29937666
TI - Rehabilitation of hemi-maxillectomy with a definite one piece hollow bulb
obturator.
AB - Maxillary intraoral defects due to surgical resection create an open link between
the oral and nasal cavities causing difficulty in deglutition, speech, and an
unaesthetic appearance. Prosthetic innervention is required to restore the needs
of speech, mastication as well as closing the oroantral communication. This
article shows a case report of systematic approach for fabrication of immediate
plate just after surgery, followed by interim feeding plate 2 weeks after
surgery, and finally definitive one piece hollow bulb obturator 6 months after
surgery.
PMID- 29937667
TI - The aberrant extraction of a maxillary canine and two lower incisors.
AB - Extractions are a common place in orthodontics. The present article discusses a
rare case, in which a left maxillary canine along with two lower incisors was
extracted. Atypical extractions such as these need to be duly justified and
thought over before being carried out. In the case mentioned, all these teeth in
question were ectopically erupted. When attempts were made to retract the canine
in its right position, it exhibited gingival recession which would only go on
increasing further as the distance from the transposed position in between the
left central and lateral incisor to the original position was considerably large.
It was planned that the 1st premolar would be converted to canine on completion
of the treatment. The lower incisors too would have shown severe periodontal
damage had attempts to align them was made. Not only were these two teeth
lingually erupted but they also were rotated along their long axis. Derotation
along with labial movement would have caused breakage of the supracrestal and
transseptal fibers resulting in periodontal breakdown leading to mobility of
these teeth. An esthetically and functionally balanced outcome was achieved
following these extractions. In the upper arch, although the midline remained
compromised, it was not worsened. In the lower arch alignment was achieved with
preservation of the intercanine width. Complicated cases such as these require a
thorough scrutiny of all available options. Whatever the treatment plan may be,
the ultimate goal of functional and esthetic balance should be achieved.
PMID- 29937668
TI - An innovative approach to the prosthodontic management of Class III mandibular
defect.
AB - Class III mandibular resection due to surgical treatment of jaw tumor produces a
discontinuity in the mandible which is severely incapacitating to the patient. It
leads to a deviation and rotation of the mandible which depends on the amount of
tissues resected the manner of surgical site closure, loss of proprioceptive
sense of occlusion, the presence, and condition of teeth, and the time of
initiation of prosthodontic therapy. These put together makes the task of
prosthodontic rehabilitation quite arduous. Guide flange prosthesis is a
comparatively simple and cost-effective method of restoring the esthetics and
function to an acceptable level. This clinical report describes an innovative and
simplified approach to impression making (sectional two-step impression) to
minimize trauma to the underlying and circumoral fragile tissues postsurgery, and
to the fabrication of buccal guide flange (wrought wire supported and reinforced
guide flange) for prosthetic rehabilitation of a patient with Class III
mandibular resection.
PMID- 29937669
TI - Maxillofacial injury from a leopard attack.
AB - Although leopards are found worldwide, the incidence of leopard attack on humans
is reported most often from India and Nepal. Usually, leopards avoid contact with
people, but humans may occasionally be targeted as prey. Animal bite wounds may
express as punctures, abrasions, tears, or avulsions. The force and bluntness of
the teeth increase the probability of a crush injury with devitalized tissue. The
clinical presentation and appropriate treatment of infected bite wounds vary
according to extent of the wound. These wounds are considered complex injuries
infected with a unique polymicrobial inoculum. As the bite injuries are commonly
found on the face, an oral and maxillofacial surgeon should be familiar with the
management of animal bites. This article reviews a case of a victim attacked by
the leopard, the treatment provided to the victim, and brief notes on the
management of such facial animal bite injuries.
PMID- 29937670
TI - Marginal resection in a case of juxtacortical chondrosarcoma of the mandible.
AB - Chondrosarcomas usually invite extensive surgical resection. These are malignant
tumors of cartilaginous origin and their involvement in the maxillofacial region
is rare. Juxtacortical chondrosarcoma, a distinct malignant cartilage-forming
tumor arising from the external surface of a bone, is extremely rare in the
mandible. Here, one such case with a relatively good prognosis is presented where
marginal resection as a surgical option yielded good result.
PMID- 29937671
TI - Fine-needle aspiration cytology as a useful diagnostic adjunct in the management
of ameloblastoma: A report of four cases.
AB - Ameloblastoma is a locally aggressive common odontogenic tumor of the jaws.
Although histopathological and radiological findings have been extensively
studied for the diagnosis of ameloblastoma, usefulness of fine-needle aspiration
cytology (FNAC) has not been explored much. Here, we have reported four cases of
ameloblastomas diagnosed by FNAC and subsequently confirmed by histopathology.
PMID- 29937672
TI - Management of mandibular fracture in pediatric patient.
AB - A pediatric mandibular fracture can cause a child severe pain and the parent or
caregiver extreme worry. While the pattern of fractures in children is similar to
adults, however, due to a number of factors, including the anatomical complexity
of the developing mandible, management of such fractures differs from that of
adults and can greatly challenge the pediatric dentist. Various treatment
modalities of managing mandibular fracture are available, such as closed/open cap
splint with circummandibular wiring, arch-bar fixation, and cementation of the
cap splint.
PMID- 29937673
TI - Oral myiasis in paralytic patients with special needs: A report of three cases.
AB - Oral myiasis is invasion of the soft tissues of oral cavity by the parasitic
larvae of the flies. This condition affects debilitated, mentally challenged
individuals. These patients are not physically or mentally endowed to ward off
flies or complain about worms burrowing their way into oral wounds. This study
describes three cases of orofacial myiasis, removal of the live maggots,
supportive treatment, and management of the cases with application of turpentine
oil and also highlights oral health care in the patients with special needs.
PMID- 29937674
TI - Revision flap surgery with compromised airway: Increasing numbers, a concern for
anesthesia.
PMID- 29937675
TI - Development of the International Alcohol Policy and Injury Index.
AB - Objective: The current work develops the International Alcohol Policy Injury
Index (IAPII) to measure the effectiveness of control policies that impact
reduction of alcohol-related injury. Methods: Using cross-sectional data on
alcohol policies from five policy domains (physical availability, drinking
context, pricing, advertising, and vehicular), injury death, and alcohol
attributable fractions (AAFs) for vehicular deaths were accessed from the WHO
database for 156 countries. A composite indicator, the International Alcohol
Policy Injury Index (IAPII), was created to assess the association between policy
and death due to injury. Findings: Controlling for per-capita alcohol
consumption, injury deaths and AAF deaths were inversely associated with four of
the five policy domains. The domains were weighted according to effectiveness and
used to construct the IAPII which produced acceptable sensitivity and
specificity. Regression results, controlling for consumption, demonstrated the
IAPII was significantly associated with AAF vehicular injury death for males, AAF
vehicular injury death for females and overall injury death at p< 0.01.
Conclusion: Findings support the IAPII as a reliable indicator of the
relationship between alcohol policies and injury deaths; the stronger the policy
the less the likelihood of both overall and vehicular injury death. Future work
should test the effectiveness of the IAPII in reducing alcohol-related injury
morbidity, which accounts for a larger share of the global burden of disease than
alcohol-related injury mortality.
PMID- 29937676
TI - Translation Synchronization via Truncated Least Squares.
AB - In this paper, we introduce a robust algorithm, TranSync, for the 1D translation
synchronization problem, in which the aim is to recover the global coordinates of
a set of nodes from noisy measurements of relative coordinates along an
observation graph. The basic idea of TranSync is to apply truncated least
squares, where the solution at each step is used to gradually prune out noisy
measurements. We analyze TranSync under both deterministic and randomized noisy
models, demonstrating its robustness and stability. Experimental results on
synthetic and real datasets show that TranSync is superior to state-of-the-art
convex formulations in terms of both efficiency and accuracy.
PMID- 29937677
TI - Dual targeting agents for Abeta plaque/P-glycoprotein and Abeta plaque/nicotinic
acetylcholine alpha4beta2* receptors-potential approaches to facilitate Abeta
plaque removal in Alzheimer's disease brain.
AB - Alzheimer's disease (AD) affects 10% of people older than 65 and is characterized
by a progressive loss of cognitive function with an abnormal accumulation of
amyloid beta (Abeta ) plaques and neurofibrillary tangles (NFT) in the brain.
Efforts to reduce brain Abeta plaques continue to be investigated as a
therapeutic approach for AD. We report here development of dual targeting agents
with affinity for Abeta plaque/P-glycoprotein (Pgp) and Abeta plaque/alpha4beta
2* nicotinic acetylcholine receptors (nAChR). These novel dual agents may be able
to efflux Abeta plaques via the paravascular (glymphatic) pathways. Ferulic acid
(FA), ferulic acid ethyl ester (FAEE), and curcumin (CUR) were used for Abeta
plaques, fexofenadine (FEX) was used as substrate for Pgp and nifrolidine (NIF)
was used for alpha4beta 2* nAChRs. Abeta plaque/alpha4beta 2* nAChR dual agent,
FA-NIF (GKS-007) exhibited IC50 = 3-6 nM for alpha4beta 2* nAChRs in [3H]cytisine
radiolabeled thalamus and frontal cortex in rat brain slices. In postmortem human
AD frontal cortex, Abeta plaques labeled with [3H]PIB, FEX-CUR showed a 35%
reduction in gray matter (GM)/white matter (WM) [3H]PIB binding, while CUR alone
showed a 50% reduction. In vivo biodistribution studies are required of the Abeta
Pgp and Abeta-alpha4beta 2* nAChRs dual targeting agents in order to evaluate
their potential as therapeutic approaches for reducing brain Abeta plaques.
PMID- 29937678
TI - Executive Functioning Predicts Reflective Functioning in Mothers.
AB - Parental reflective functioning (PRF) describes a parent's capacity for
considering both their own and their child's thoughts, feelings, and behaviors,
which can help parents to guide interactions with children. Given the cognitive
demands of keeping infants in mind whilst caregiving, we examined the association
between aspects of executive function (i.e., working memory and set-shifting) and
PRF (employing the Parental Reflective Functioning Questionnaire) in recent
mothers. In Study 1 (N=50), we found that better working memory was associated
with higher levels of maternal interest and curiosity in their child's feelings.
In Study 2 (N=68), we found that visual working memory and set-shifting capacity
were also associated with higher levels of maternal interest and curiosity in
their child's thoughts and feelings. Our results provide preliminary support for
the association between executive processes and maternal reflective functioning.
The implications of these findings and important future directions are discussed,
including advancing our understanding of executive processes and PRF to support
the broader family system.
PMID- 29937679
TI - Parents' Perspectives on Radicalization: A Qualitative Study.
AB - Radicalization of young people might be influenced by the way parents react
towards the development of political or religious ideals. However, these
reactions have hardly been explored. This study aimed to discover how parents
reacted to the development of extreme ideals, and why they responded in the way
that they did. To gain knowledge about the influence of parents on adolescents
who developed extreme ideals, 82 in-depth interviews were held with adolescents
and young adults who held extreme ideals. Interviews were also held with the
parents or siblings of each adolescent and young adult. In line with parenting
style theory, it was found that parents react in four possible ways: (1) by
rejecting, (2) applauding, (3) ignoring, or (4) discussing the (extreme) ideals
of their children. Few parents discuss ideals and values with their child, and
this paper tries to show why (e.g., powerlessness, disassociation, occupation
with other problems, believing it to be a phase that will pass, or that their
reaction would not help). Most parents struggle to cope with radicalization and
do not know how to react. Support and control are potentially important tools for
parents to use to combat the development of extreme ideology.
PMID- 29937681
TI - Origin and significance of cosmogenic signatures in vesicles of lunar basalt
15016.
AB - Lunar basalt 15016 (~3.3 Ga) is among the most vesicular (50% by volume) basalts
recovered by the Apollo missions. We investigated the possible occurrence of
indigenous lunar nitrogen and noble gases trapped in vesicles within basalt
15016, by crushing several cm-sized chips. Matrix/mineral gases were also
extracted from crush residues by fusion with a CO 2 laser. No magmatic/primordial
component could be identified; all isotope compositions, including those of
vesicles, pointed to a cosmogenic origin. We found that vesicles contained ~0.2%,
~0.02%, ~0.002%, and ~0.02% of the total amount of cosmogenic 21Ne, 38Ar, 83Kr,
and 126Xe, respectively, produced over the basalt's 300 Myr of exposure.
Diffusion/recoil of cosmogenic isotopes from the basaltic matrix/minerals to
intergrain joints and vesicles is discussed. The enhanced proportion of
cosmogenic Xe isotopes relative to Kr detected in vesicles could be the result of
kinetic fractionation, through which preferential retention of Xe isotopes over
Kr within vesicles might have occurred during diffusion from the vesicle volume
to the outer space through microleaks. This study suggests that cosmogenic loss,
known to be significant for 3He and 21Ne, and to a lesser extent for 36Ar (Signer
et al. 1977), also occurs to a negligible extent for the heaviest noble gases Kr
and Xe.
PMID- 29937680
TI - Socio-demographic Correlates of Fathers' and Mothers' Parenting Behaviors.
AB - In the present study, we investigated whether fathers' and mothers' parenting
behavior is differentially related to parental factors (such as age and
employment), child factors (age and gender) as well as social support. Parents
reported on their use of a broad range of parenting behaviors, including
affection, responsivity, explaining, autonomy, support, rewarding, and punishing.
We used survey data from the Netherlands for 1197 mothers and 903 fathers of
children aged 2 to 17. Seemingly unrelated regression analyses were conducted to
combine the regression results on the separate subsamples (fathers and mothers)
and to test for differences in the coefficients between those subsamples. Our
expectation that the parenting behavior of fathers is more dependent on parents'
characteristics, children's characteristics, and social support than that of
mothers was only partly confirmed by the results of our analysis. In general, our
results suggest that fathers' parenting behaviors seem to be associated with
parental and child characteristics and contextual factors in ways that are
similar to how these factors are associated with mothers' parenting behaviors.
Results are discussed in relation to the roles and expectations associated with
motherhood and fatherhood.
PMID- 29937682
TI - Supercritical CO2 extraction in chia oils production: impact of process duration
and co-solvent addition.
AB - This study was conducted to show impact of supercritical fluid extraction using
pure SC-CO2 or SC-CO2 enriched by 2, 6, and 10% of acetone, simultaneously varied
by the extraction time (1 vs. 5 h), on the quality of chia seed oils. Obtained
oils were relatively similar in the fatty acid composition, but they differed in
total content of phytochemicals (from 4956 to 6391 mg/kg of oil). Among them,
three oils were the most different: oil extracted 1 h with pure SC-CO2 (the most
abundant in squalene, sterols, and tocopherols), oil extracted 5 h with pure SC
CO2 (the poorest in squalene, polyphenols, and carotenoids, with medium level of
sterols and tocopherols) and oil extracted 1 h with SC-CO2 enriched by 10%
acetone (the most abundant in polyphenols and carotenoids). Such unique chia oils
can be valuable for special market needs, such as cosmetics, pharmaceuticals,
functional food or diet supplement production.
PMID- 29937683
TI - Dried strawberries as a high nutritional value fruit snack.
AB - The purpose of this study was to determine the possibility of using a chokeberry
juice concentrate as a component of osmotic solution and convection-microwave
vacuum drying applying to obtain dried pro-health-promoting strawberries. The
research material was Honeoye strawberries, which were dehydrated in sucrose and
sucrose with chokeberry juice concentrate addition, and then subjected to
microwave-convection-vacuum or freeze-drying. Analyses were conducted to
determine the influence of the applied processes on vitamin C content, total
polyphenols, antioxidant activity, and sensory properties in dried fruit. Study
results confirmed the possibility of using a chokeberry juice concentrate as a
component of the osmotic solution, especially with regard to polyphenolics
content and antioxidant activity. In addition, convection-microwave-vacuum drying
was shown to be a promising technology for the production of dried strawberries,
with high pro-health potential and acceptable sensory qualities.
PMID- 29937684
TI - The effect of microbial activity on soil water diffusivity.
AB - : In this study, we explored the effects of microbial activity on the evaporation
of water from cores of a sandy soil under laboratory conditions. We applied
treatments to stimulate microbial activity by adding different amounts of
synthetic analogue root exudates. For comparison, we used soil samples without
synthetic root exudates as control and samples treated with mercuric chloride to
suppress microbial activity. Our results suggest that increasing microbial
activity reduces the rate of evaporation from soil. Estimated diffusivities in
soil with the largest amounts of added root exudates were one third of those
estimated in samples where microbial activity was suppressed by adding mercuric
chloride. We discuss the effect of our results with respect to water uptake by
roots. Highlights: We explored effects of microbial activity on the evaporation
of water from cores of a sandy soil.We found the effect of microbial activity on
water release characteristic was small.Increasing microbial activity reduced
evaporation from soil, while microbial suppression increased it.Effect of
microbial activity on root water uptake was estimated to be equivalent to a
change in soil structure.
PMID- 29937685
TI - The Impact of Universal Health Coverage on Households' Consumption and Savings in
Thailand.
AB - This paper studies the impact of Thailand's Universal Health Coverage Scheme
(UCS) on households' consumption and savings by using a synthetic panel data
approach. Using difference-in-differences estimation, this study finds that, in
the short run, the UCS had little or no impact on either households' savings or
households' consumption expenditures. In the long run, the UCS still had no
effect on savings (unless savings is defined to include consumption of durable
goods), but there is evidence of an increase in consumption, especially
consumption of durable goods. These effects are generally consistent with
economic theory. The provision of health care coverage at little or no cost to
previously uninsured households has an income effect that will increase both
savings and consumption and a risk reduction effect that will reduce
precautionary savings and thus increase consumption. These two effects on savings
are of opposite sign and appear to cancel each other out, while both effects on
consumption are positive and so appear to increase consumption, at least in the
long run.
PMID- 29937686
TI - A taxonomy of quality assessment methods for volunteered and crowdsourced
geographic information.
AB - The growing use of crowdsourced geographic information (CGI) has prompted the
employment of several methods for assessing information quality, which are aimed
at addressing concerns on the lack of quality of the information provided by non
experts. In this work, we propose a taxonomy of methods for assessing the quality
of CGI when no reference data are available, which is likely to be the most
common situation in practice. Our taxonomy includes 11 quality assessment methods
that were identified by means of a systematic literature review. These methods
are described in detail, including their main characteristics and limitations.
This taxonomy not only provides a systematic and comprehensive account of the
existing set of methods for CGI quality assessment, but also enables researchers
working on the quality of CGI in various sources (e.g., social media, crowd
sensing, collaborative mapping) to learn from each other, thus opening up avenues
for future work that combines and extends existing methods into new application
areas and domains.
PMID- 29937687
TI - Fracturing the Penal State: State Actors and the Role of Conflict in Penal
Change.
AB - The concept of a penal or carceral state has quickly become a staple in
punishment and criminal justice literature. However, the concept, which suffers
from a proliferation of meanings and is frequently undefined, gives readers the
impression that there is a single, unified, and actor-less state responsible for
punishment. This contradicts the thrust of recent punishment literature, which
emphasizes fragmentation, variegation, and constant conflict across the actors
and institutions that shape penal policy and practice. Using a case study of late
century Michigan, this paper develops an analytical approach that fractures the
penal state, demonstrating that, far from a unified entity, it is a messy, often
conflicted amalgamation of the various branches and actors in charge of
punishment and the ways they resist the aims and policies sought by their fellow
state actors. Ultimately, we argue that fracture is itself a variable that
scholars must measure empirically and incorporate into their accounts of penal
change.
PMID- 29937688
TI - Chemical Glucosylation of Labile Natural Products Using a (2-Nitrophenyl)acetyl
Protected Glucosyl Acetimidate Donor.
AB - The synthesis of (2-nitrophenyl)acetyl (NPAc)-protected glucosyl donors is
described that were designed for the neighboring-group assisted glucosylation of
base-labile natural products also being sensitive to hydrogenolysis.
Glycosylation conditions were optimized using a trichloroacetimidate glucosyl
donor, and cyclohexylmethanol and (+)-menthol as model acceptors. The approach
was then extended to a one-pot procedure for the synthesis of 1,2-trans
glycosides. This method was finally applied for improved synthesis of the masked
mycotoxin T2-O-beta,d-glucoside.
PMID- 29937689
TI - 1,2-Addition of Diethylzinc to a Bis(Imidazolyl)ketone Ligand.
AB - In this study, the selective 1,2-addition of diethylzinc to the ketone
functionality of BMdiPhIK [bis(1-methyl-4,5-diphenylimidazolyl)ketone] is shown.
The reaction product is isolated in a dimeric form with a planar Zn2(u-O)2-motif
keeping the two monomers together. This compound can serve as a model for
reactive intermediates in the catalytic alkylation of ketones with diorganozinc
reagents. Hydrolysis of this binuclear zinc compound leads to isolation of the C
alkylated product in 89 % yield. A reaction pathway is proposed in which BMdiPhIK
initially coordinates to diethylzinc as a bidentate bis(nitrogen) ligand. This is
followed by the homolytic cleavage of the Zn-Et bond and in-cage recombination of
the Et-radical and the Zn-coordinated ligand-centered radical, which is mainly
localized on the carbonyl moiety of the ligand.
PMID- 29937690
TI - Coordination of 3-Methylindole-Based Tripodal Tetraphosphine Ligands to
Iron(+II), Cobalt(+II), and Nickel(+II) and Investigations of their Subsequent
Two-Electron Reduction.
AB - We report the coordination chemistry of indole based tripodal tetraphosphine
ligands to iron(II), cobalt(II) and nickel(II). These complexes are formed by
simple synthetic protocols and were characterized by a combination of
spectroscopic techniques and single-crystal X-ray analysis. The molecular
structures as determined by X-ray diffraction show that the geometry of the
nickel and cobalt complexes are distorted trigonal bipyramidal. The monocationic
iron(II) complexes also have distorted trigonal bipyramidal geometries, but the
dicationic analogue has an octahedral geometry. Two-electron reduction of the
cobalt(+II) and the nickel(+II) complexes in the presence of N2 did not lead to
the coordination of N2. In contrast, two-electron reduction of the iron(+II)
complexes did lead to coordination of dinitrogen to the iron center. The Fe0N2L1H
complex has a trigonal bipyramidal geometry, and the N-N bond length of the
coordinated dinitrogen ligand is longer than that of free dinitrogen, indicating
that coordination to this iron(0) complex results in activation of the N=N bond.
PMID- 29937692
TI - Gravitational waves in modified teleparallel theories of gravity.
AB - Teleparallel theory of gravity and its modifications have been studied
extensively in literature. However, gravitational waves has not been studied
enough in the framework of teleparallelism. In the present study, we discuss
gravitational waves in general theories of teleparallel gravity containing the
torsion scalar T, the boundary term B and a scalar field phi . The goal is to
classify possible new polarizations generalizing results presented in Bamba et
al. (Phys Lett B 727:194-198, arXiv:1309.2698, 2013). We show that, if the
boundary term is minimally coupled to the torsion scalar and the scalar field,
gravitational waves have the same polarization modes of General Relativity.
PMID- 29937691
TI - Nickel-Alkyl Complexes with a Reactive PNC-Pincer Ligand.
AB - Based on previous work related to the design and application of rigid tridentate
phosphine-pyridine-phenyl coordination offered by a PNC-pincer ligand upon
cyclometalation to nickel, the synthesis, spectroscopic and solid state
characterization and redox-reactivity of two NiII(PNC) complexes featuring either
a methyl (2CH3 ) or CF3 co-ligand (2CF3 ) are described. One-electron oxidation
is proposed to furnish C-C reductive elimination, as deduced from a combined
chemical, electrochemical, spectroscopic and computational study. One-electron
reduction results in a ligand-centered radical anion, as supported by
electrochemistry, UV spectroelectrochemistry, EPR spectroscopy, and DFT
calculations. This further attenuates the breadth of chemical reactivity offered
by such PNC-pincer ligands.
PMID- 29937694
TI - Mass probation: Toward a more robust theory of state variation in punishment.
AB - Scholarship on the expansion of the U.S. carceral state has primarily focused on
imprisonment rates. Yet the majority of adults under formal criminal justice
control are on probation, an "alternative" form of supervision. This article
develops the concept of mass probation and builds a typology of state control
regimes that theorizes both the scale and type of punishment states employ.
Drawing on Bureau of Justice Statistics data from 1980 and 2010, I analyze
whether mass probation developed in the same places, affecting the same
demographic groups and driven by the same criminal justice trends, as mass
imprisonment. The results show that mass probation was a unique state
development, expanding in unusual places like Minnesota and Washington. The
conclusions argue for a reimagining of the causes and consequences of the
carceral state to incorporate the expansion of probation.
PMID- 29937695
TI - The Hearing Voices Movement as Postmodern Religion-Making: Meaning, Power,
Sacralization, Identity.
AB - Over the past 40 or 50 years, scholars of religion have frequently attempted to
use the tools of social science to analyse, describe, and explain the relevance
and persistence of religion in the modern world. With the bold predictions of the
secularization thesis as their stimuli, many sociologists and anthropologists
preferred to focus on the under-explored, marginalized, or otherwise unexpected
expressions of religion within those ostensibly secularizing contexts. Such
studies have led to an abundance of theories and accompanying terms: "implicit
religion," "vernacular religion," "vicarious religion," "lived religion,"
"popular religion," and "folk religion." Without choosing any one of these, but
owing much to their shared-arguably postmodern-themes of commonplace sacrality
and personal empowerment, this paper seeks to explore the possibility of the
Hearing Voices Movement (HVM) as an example of religion-making. HVM is a growing
force of "voice-hearers" from at least 28 countries who have formed user-led
networks for activism and mental health recovery. More importantly, it is argued
that HVM blends meaning-making, postmodern notions of identity in relation to
power structures, and ritual embodiment, resulting in a striking example of
sociologist Hans Mol's notion of religion as a sacralizing process.
PMID- 29937693
TI - Genetics-based methods for agricultural insect pest management.
AB - The sterile insect technique is an area-wide pest control method that reduces
agricultural pest populations by releasing mass-reared sterile insects, which
then compete for mates with wild insects. Contemporary genetics-based
technologies use insects that are homozygous for a repressible dominant lethal
genetic construct rather than being sterilized by irradiation.Engineered strains
of agricultural pest species, including moths such as the diamondback moth
Plutella xylostella and fruit flies such as the Mediterranean fruit fly Ceratitis
capitata, have been developed with lethality that only operates on
females.Transgenic crops expressing insecticidal toxins are widely used; the
economic benefits of these crops would be lost if toxin resistance spread through
the pest population. The primary resistance management method is a high
dose/refuge strategy, requiring toxin-free crops as refuges near the insecticidal
crops, as well as toxin doses sufficiently high to kill wild-type insects and
insects heterozygous for a resistance allele.Mass-release of toxin-sensitive
engineered males (carrying female-lethal genes), as well as suppressing
populations, could substantially delay or reverse the spread of resistance. These
transgenic insect technologies could form an effective resistance management
strategy.We outline some policy considerations for taking genetic insect control
systems through to field implementation.
PMID- 29937696
TI - DTI BASED STRUCTURAL DAMAGE CHARACTERIZATION FOR DISORDERS OF CONSCIOUSNESS.
AB - MRI Diffusion Tensor Imaging (DTI) has been recently proposed as a highly
discriminative measurement to detect structural damages in Disorders of
Consciousness patients (Vegetative State/Unresponsive Wakefulness Syndrome
(VS/UWS) and Minimally Consciousness State-MCS). In the DTI analysis, certain
tensor features are often used as simplified scalar indices to represent these
alterations. Those characteristics are mathematically and statistically more
tractable than the full tensors. Nevertheless, most of these quantities are based
on a tensor diffusivity estimation, the arithmetic average among the different
strengths of the tensor orthogonal directions, which is supported on a symmetric
linear relationship among the three directions, an unrealistic assumption for
severely damaged brains. In this paper, we propose a new family of scalar
quantities based on Generalized Ordered Weighted Aggregations (GOWA) to
characterize morphological damages. The main idea is to compute a tensor
diffusitivity estimation that captures the deviations in the water diffusivity
associated to damaged tissue. This estimation is performed by weighting and
combining differently each tensor orthogonal strength. Using these new scalar
quantities we construct an affine invariant DTI tensor feature using regional
tissue histograms. An evaluation of these new scalar quantities on 48 patients
(23 VS/UWS and 25 MCS) was conducted. Our experiments demonstrate that this new
representation outperforms state-of-the-art tensor based scalar representations
for characterization and classification problems.
PMID- 29937697
TI - Just Before I Recognize Myself: The Role of Featural and Multisensory Cues
Leading up to Explicit Mirror Self-Recognition.
AB - Leading up to explicit mirror self-recognition, infants rely on two crucial
sources of information: the continuous integration of sensorimotor and
multisensory signals, as when seeing one's movements reflected in the mirror, and
the unique facial features associated with the self. While visual appearance and
multisensory contingent cues may be two likely candidates of the processes that
enable self-recognition, their respective contribution remains poorly understood.
In this study, 18-month-old infants saw side-by-side pictures of themselves and a
peer, which were systematically and simultaneously touched on the face with a
hand. While watching the stimuli, the infant's own face was touched either in
synchrony or out of synchrony and their preferential looking behavior was
measured. Subsequently, the infants underwent the mirror-test task. We
demonstrated that infants who were coded as nonrecognizers at the mirror test
spent significantly more time looking at the picture of their own face compared
to the other-face, irrespective of whether the multisensory input was synchronous
or asynchronous. Our results suggest that right before the onset of mirror self
recognition, featural information about the self might be more relevant in the
process of recognizing one's face, compared to multisensory cues.
PMID- 29937698
TI - Characterization by Scanning Precession Electron Diffraction of an Aggregate of
Bridgmanite and Ferropericlase Deformed at HP-HT.
AB - Scanning precession electron diffraction is an emerging promising technique for
mapping phases and crystal orientations with short acquisition times (10-20
ms/pixel) in a transmission electron microscope similarly to the Electron
Backscattered Diffraction (EBSD) or Transmission Kikuchi Diffraction (TKD)
techniques in a scanning electron microscope. In this study, we apply this
technique to the characterization of deformation microstructures in an aggregate
of bridgmanite and ferropericlase deformed at 27 GPa and 2,130 K. Such a sample
is challenging for microstructural characterization for two reasons: (i) the
bridgmanite is very unstable under electron irradiation, (ii) under high stress
conditions, the dislocation density is so large that standard characterization by
diffraction contrast are limited, or impossible. Here we show that detailed
analysis of intracrystalline misorientations sheds some light on the deformation
mechanisms of both phases. In bridgmanite, deformation is accommodated by
localized, amorphous, shear deformation lamellae whereas ferropericlase undergoes
large strains leading to grain elongation in response to intense dislocation
activity with no evidence for recrystallization. Plastic strain in ferropericlase
can be semiquantitatively assessed by following kernel average misorientation
distributions.
PMID- 29937699
TI - MERRILL: Micromagnetic Earth Related Robust Interpreted Language Laboratory.
AB - Complex magnetic domain structures and the energy barriers between them are
responsible for pseudo-single-domain phenomena in rock magnetism and contribute
significantly to the magnetic remanence of paleomagnetic samples. This article
introduces MERRILL, an open source software package for three-dimensional
micromagnetics optimized and designed for the calculation of such complex
structures. MERRILL has a simple scripting user interface that requires little
computational knowledge to use but provides research strength algorithms to model
complex, inhomogeneous domain structures in magnetic materials. It uses a finite
element/boundary element numerical method, optimally suited for calculating
magnetization structures of local energy minima (LEM) in irregular grain
geometries that are of interest to the rock and paleomagnetic community. MERRILL
is able to simulate the magnetic characteristics of LEM states in both single
grains, and small assemblies of interacting grains, including saddle-point paths
between nearby LEMs. Here the numerical model is briefly described, and an
overview of the scripting language and available commands is provided. The open
source nature of the code encourages future development of the model by the
scientific community.
PMID- 29937700
TI - Evaluation of marine zooplankton community structure through environmental DNA
metabarcoding.
AB - Zooplankton dominate the abundance and biomass of multicellular animals in
pelagic marine environments; however, traditional methods to characterize
zooplankton communities are invasive and laborious. This study compares
zooplankton taxonomic composition revealed through metabarcoding of the
cytochrome oxidase I (COI) and 18S rRNA genes to traditional morphological
identification by microscopy. Triplicates of three different sample types were
collected from three coral reef sites in the Florida Keys National Marine
Sanctuary: (1) 1 L surface seawater samples prefiltered through 3 MUm filters and
subsequently collected on 0.22 MUm filters for eDNA (PF-eDNA); (2) 1 L surface
seawater samples filtered on 0.22 MUm pore-size filters (environmental DNA;
eDNA), and (3) zooplankton tissue samples from 64 MUm, 200 MUm, and 500 MUm mesh
size net tows. The zooplankton tissue samples were split, with half identified
morphologically and tissue DNA (T-DNA) extracted from the other half. The COI and
18S rRNA gene metabarcoding of PF-eDNA, eDNA, and T-DNA samples was performed
using Illumina MiSeq. Of the families detected with COI and 18S rRNA gene
metabarcoding, 40% and 32%, respectively, were also identified through
morphological assessments. Significant differences in taxonomic composition were
observed between PF-DNA, eDNA, and T-DNA with both genetic markers. PF-eDNA
resulted in detection of fewer taxa than the other two sample types; thus,
prefiltering is not recommended. All dominant copepod taxa (> 5% of total
abundance) were detected with eDNA, T-DNA, and morphological assessments,
demonstrating that eDNA metabarcoding is a promising technique for future
biodiversity assessments of pelagic zooplankton in marine systems.
PMID- 29937701
TI - Coresidence with a child and happiness among older widows in Europe: Does gender
of the child matter?
AB - Both coresidence patterns and the reported well-being of older people vary widely
across Europe for a variety of economic, cultural, and historical factors. We
investigate how far 2 indicators of well-being, happiness and life satisfaction,
vary according to whether or not older women live with their children and, in
particular, with son(s) or daughter(s). We compare outcomes for women who are
unpartnered widows, the great majority of whom will have had children, so those
with and without coresident children may be compared. We use data for 34
countries in Europe by combining 7 waves of the European Social Survey for the
period 2002-2014 (N = 18,500). We control for a range of other variables known to
be associated with well-being including health status, socioeconomic position,
and social support. Results show that widows living with a child were happier
than those living without a child (generally alone) but that in Eastern and
Southern Europe it was only living with a daughter that had this positive effect.
Older age was associated with higher levels of happiness and life satisfaction.
Other associations, and regional differences, were as expected with lower levels
of happiness in Eastern Europe and for those with poorer health and fewer social
resources. These findings indicate the important influence of contextual factors
on associations between living arrangements and the well-being of older people
and a need for further work on possible negative impacts of living alone on the
well-being of older Europeans.
PMID- 29937702
TI - The impact of residential change and housing stability on recidivism: pilot
results from the Maryland Opportunities through Vouchers Experiment (MOVE).
AB - Objectives: This article provides a description and preliminary assessment of the
Maryland Opportunities through Vouchers Experiment (MOVE), a randomized housing
mobility program for former prisoners designed to test whether residential
relocation far away from former neighborhoods, incentivized through the provision
of a housing subsidy, can yield reductions in recidivism. Methods: The MOVE
program was implemented as a randomized controlled trial. Participants were
recruited from four different Maryland prisons and randomly assigned to
experimental groups. In the first iteration of the experiment, treatment group
participants received 6 months of free housing away from their home jurisdiction
and control group participants received free housing back in their home
jurisdiction. In the second iteration of the experiment, the treatment group
remained the same and the control condition was redesigned to represent the
status quo and did not receive free housing. Analyses were conducted of one-year
rearrest rates. Results: With respect to reductions in recidivism, pilot results
suggest that there is some benefit to moving and a benefit to receiving free
housing. Rearrest was lower among the treatment group of movers than the non
movers, and was also lower for non-movers who received free housing versus non
movers who did not receive housing. Conclusions: To the extent that pilot results
can be validated and replicated in a full-scale implementation of the MOVE
program, policies that provide greater access to housing assistance for formerly
incarcerated individuals may yield substantial public safety benefits,
particularly housing opportunities located far away from former neighborhoods.
PMID- 29937703
TI - NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation
reveals treatment-reversible lipid and amino acid metabolism alterations.
AB - Introduction: Elucidating molecular alterations due to mitochondrial Complex I
(CI) mutations may help to understand CI deficiency (CID), not only in
mitochondriopathies but also as it is caused by drugs or associated to many
diseases. Objectives: CID metabolic expression was investigated in Leber's
hereditary optic neuropathy (LHON) caused by an inherited mutation of CI.
Methods: NMR-based metabolomics analysis was performed in intact skin fibroblasts
from LHON patients. It used several datasets: one-dimensional 1H-NMR spectra, two
dimensional 1H-NMR spectra and quantified metabolites. Spectra were analysed
using orthogonal partial least squares-discriminant analysis (OPLS-DA), and
quantified metabolites using univariate statistics. The response to idebenone
(IDE) and resveratrol (RSV), two agents improving CI activity and mitochondrial
functions was evaluated. Results: LHON fibroblasts had decreased CI activity (-
43%, p < 0.01). Metabolomics revealed prominent alterations in LHON including the
increase of fatty acids (FA), polyunsaturated FA and phosphatidylcholine with a
variable importance in the prediction (VIP) > 1 in OPLS-DA, p < 0.01 in
univariate statistics, and the decrease of amino acids (AA), predominantly
glycine, glutamate, glutamine (VIP > 1) and alanine (VIP > 1, p < 0.05). In LHON,
treatment with IDE and RSV increased CI activity (+ 40 and + 44%, p < 0.05). IDE
decreased FA, polyunsaturated FA and phosphatidylcholine (p < 0.05), but did not
modified AA levels. RSV decreased polyunsaturated FA, and increased several AA
(VIP > 1 and/or p < 0.05). Conclusion: LHON fibroblasts display lipid and amino
acid metabolism alterations that are reversed by mitochondria-targeted
treatments, and can be related to adaptive changes. Findings bring insights into
molecular changes induced by CI mutation and, beyond, CID of other origins.
PMID- 29937704
TI - Using the egg parasitoid Anastatus bifasciatus against the invasive brown
marmorated stink bug in Europe: can non-target effects be ruled out?
AB - The brown marmorated stink bug, Halyomorpha halys (Stal) (Hemiptera:
Pentatomidae), has been causing massive damage to various fruit and vegetable
crops after its arrival in the USA, and more recently in Europe. To provide an
alternative control measure to pesticides, the native egg parasitoid Anastatus
bifasciatus (Geoffroy) (Hymenoptera: Eupelmidae) was considered as a candidate
biological control agent for inundative releases in Europe. In the risk
assessment study presented here, all nine heteropteran and 14 out of 19 tested
lepidopteran non-target species produced viable A. bifasciatus offspring. The
proportion of A. bifasciatus females producing offspring did not differ between
non-target and target for 19 out of the 28 non-target species. Larger host eggs
corresponded to increased female-biased sex ratio of the offspring as well as an
increase in size, particularly for females, with hind tibia lengths varying from
645.5 +/- 46 to 1084 +/- 28.5 MUm. Larger females were also found to have higher
offspring production and increased life expectancy. The results of this study
confirmed the polyphagous nature of A. bifasciatus and suggest that a number of
non-target species, including Lepidoptera of conservation interest, may be
attacked in the field. Thus, non-target effects cannot entirely be ruled out, but
more information is needed from semi-field and field studies to fully assess
potential environmental risks due to inundative releases of this native
parasitoid.
PMID- 29937705
TI - Landscape configuration affects herbivore-parasitoid communities in oilseed rape.
AB - It is crucial to consider the effects of large-scale drivers on species presences
and ecological interactions to understand what structures communities. In our
study, we investigated how the species composition and the potential interaction
networks of herbivore and parasitoid communities in oilseed rape fields are
affected by agricultural landscape characteristics. Insect communities of 26
winter oilseed rape fields in southern Sweden were captured in water traps over a
continuous time span of 30 +/- 2 days. In total, 31% of the variation in the
composition of herbivore host communities was explained by a combination of the
surrounding oilseed rape area in the study year and the previous year and
distance to the nearest forest. The oilseed rape area in the study year and
distance to forest also explained 14% of the variation in the composition of
parasitoid communities. Distance to the nearest forest together with the area of
oilseed rape in the previous year explained 45% of the variation in asymmetry of
interaction webs. These results indicate that several measures of landscape
configuration are important both for the composition of host and parasitoid
communities and also for the structure of interaction networks. Our results
support the view that it is an appropriate strategy to cultivate oilseed rape in
landscapes that are far away from forests, in order to minimize recolonization by
pest species and at the same time to attract parasitoid species from the open
landscape.
PMID- 29937706
TI - Chemoenzymatic Approaches to the Synthesis of the Calcimimetic Agent Cinacalcet
Employing Transaminases and Ketoreductases.
AB - Several chemoenzymatic routes have been explored for the preparation of
cinacalcet, a calcimimetic agent. Transaminases (TAs) and ketoreductases (KREDs)
turned out to be useful biocatalysts for the preparation of key optically active
precursors. Thus, the asymmetric amination of 1-acetonaphthone yielded an
enantiopure (R)-amine, which can be alkylated in one step to yield cinacalcet.
Alternatively, the bioreduction of the same ketone resulted in an enantiopure (S)
alcohol, which was easily converted into the previous (R)-amine. In addition, the
reduction was efficiently performed with the KRED and its cofactor co-immobilized
on the same porous surface. This self-sufficient heterogeneous biocatalyst
presented an accumulated total turnover number (TTN) for the cofactor of 675
after 5 consecutive operational cycles. Finally, in a preparative scale synthesis
the TA-based approach was performed in aqueous medium and led to enantiopure
cinacalcet in two steps and 50% overall yield.
PMID- 29937707
TI - A Digital Hardware Realization for Spiking Model of Cutaneous Mechanoreceptor.
AB - Inspired by the biology of human tactile perception, a hardware neuromorphic
approach is proposed for spiking model of mechanoreceptors to encode the input
force. In this way, a digital circuit is designed for a slowly adapting type I
(SA-I) and fast adapting type I (FA-I) mechanoreceptors to be implemented on a
low-cost digital hardware, such as field-programmable gate array (FPGA). This
system computationally replicates the neural firing responses of both afferents.
Then, comparative simulations are shown. The spiking models of mechanoreceptors
are first simulated in MATLAB and next the digital neuromorphic circuits
simulated in VIVADO are also compared to show that obtained results are in good
agreement both quantitatively and qualitatively. Finally, we test the performance
of the proposed digital mechanoreceptors in hardware using a prepared
experimental set up. Hardware synthesis and physical realization on FPGA indicate
that the digital mechanoreceptors are able to replicate essential characteristics
of different firing patterns including bursting and spiking responses of the SA-I
and FA-I mechanoreceptors. In addition to parallel computation, a main advantage
of this method is that the mechanoreceptor digital circuits can be implemented in
real-time through low-power neuromorphic hardware. This novel engineering
framework is generally suitable for use in robotic and hand-prosthetic
applications, so progressing the state of the art for tactile sensing.
PMID- 29937708
TI - Top-Down Cognitive and Linguistic Influences on the Suppression of Spontaneous
Otoacoustic Emissions.
AB - Auditory sensation is often thought of as a bottom-up process, yet the brain
exerts top-down control to affect how and what we hear. We report the discovery
that the magnitude of top-down influence varies across individuals as a result of
differences in linguistic background and executive function. Participants were 32
normal-hearing individuals (23 female) varying in language background (11 English
monolinguals, 10 Korean-English late bilinguals, and 11 Korean-English early
bilinguals), as well as cognitive abilities (working memory, cognitive control).
To assess efferent control over inner ear function, participants were presented
with speech-sounds (e.g., /ba/, /pa/) in one ear while spontaneous otoacoustic
emissions (SOAEs) were measured in the contralateral ear. SOAEs are associated
with the amplification of sound in the cochlea, and can be used as an index of
top-down efferent activity. Individuals with bilingual experience and those with
better cognitive control experienced larger reductions in the amplitude of SOAEs
in response to speech stimuli, likely as a result of greater efferent suppression
of amplification in the cochlea. This suppression may aid in the critical task of
speech perception by minimizing the disruptive effects of noise. In contrast,
individuals with better working memory exert less control over the cochlea,
possibly due to a greater capacity to process complex stimuli at later stages.
These findings demonstrate that even peripheral mechanics of auditory perception
are shaped by top-down cognitive and linguistic influences.
PMID- 29937709
TI - Biochemical, Anatomical, and Pharmacological Characterization of Calcitonin-Type
Neuropeptides in Starfish: Discovery of an Ancient Role as Muscle Relaxants.
AB - Calcitonin (CT) is a peptide hormone released by the thyroid gland that regulates
blood Ca2+ levels in mammals. The CT gene is alternatively spliced, with one
transcript encoding CT and another transcript encoding the CT-like neuropeptide
calcitonin-gene related peptide (alpha-CGRP), which is a powerful vasodilator.
Other CT-related peptides in vertebrates include adrenomedullin, amylin, and
intermedin, which also act as smooth muscle relaxants. The evolutionary origin of
CT-type peptides has been traced to the bilaterian common ancestor of protostomes
and deuterostomes and a CT-like peptide (DH31) has been identified as a diuretic
hormone in some insect species. However, little is known about the physiological
roles of CT-type peptides in other invertebrates. Here we characterized a CT-type
neuropeptide in a deuterostomian invertebrate-the starfish Asterias rubens
(Phylum Echinodermata). A CT-type precursor cDNA (ArCTP) was sequenced and the
predicted structure of the peptide (ArCT) derived from ArCTP was confirmed using
mass spectrometry. The distribution of ArCTP mRNA and the ArCT peptide was
investigated using in situ hybridization and immunohistochemistry, respectively,
revealing stained cells/processes in the nervous system, digestive system, and
muscular organs, including the apical muscle and tube feet. Investigation of the
effects of synthetic ArCT on in vitro preparations of the apical muscle and tube
feet revealed that it acts as a relaxant, causing dose-dependent reversal of
acetylcholine-induced contraction. Furthermore, a muscle relaxant present in
whole-animal extracts of another starfish species, Patiria pectinifera, was
identified as an ortholog of ArCT and named PpCT. Consistent with the expression
pattern of ArCTP in A. rubens, RT-qPCR revealed that in P. pectinifera the PpCT
precursor transcript is more abundant in the radial nerve cords than in other
tissues/organs analyzed. In conclusion, our findings indicate that the
physiological action of CT-related peptides as muscle relaxants in vertebrates
may reflect an evolutionarily ancient role of CT-type neuropeptides that can be
traced back to the common ancestor of deuterostomes.
PMID- 29937710
TI - Pretreatment With Risperidone Ameliorates Systemic LPS-Induced Oxidative Stress
in the Cortex and Hippocampus.
AB - Risperidone (RIS), an atypical antipsychotic has been found to show anti
inflammatory effect against lipopolysaccharide (LPS)-induced inflammation. In
vitro study has revealed that RIS inhibits the LPS-induced reactive oxygen
species (ROS) formation. We investigated the antioxidant effects of RIS on LPS
induced oxidative stress markers in Swiss albino mice. Ten weeks old male Swiss
albino mice (30 +/- 2 g) were pretreated with either distilled water (control) or
RIS (3 mg/kg) for 7 days. On day 8, animals were challenged with a single dose of
LPS (0.8 mg/kg) while control animals received distilled water only. The animals
were sacrificed after 24 h of LPS administration and tissue samples were
collected. RIS administration significantly (p < 0.05) reduced the LPS-induced
elevated levels of lipid peroxidation product malondialdehyde (MDA), advanced
protein oxidation products, and nitric oxide (NO) in the cortex. Catalase (CAT)
and superoxide dismutase (SOD) levels were also diminished while the level of
glutathione (GSH) was enhanced. Hippocampus data showed that RIS significantly (p
< 0.05) reduced the LPS-induced increased levels of MDA and NO, and SOD activity.
Our results suggest that LPS-induced neuronal oxidative damage can be alleviated
by the pretreatment with RIS and the effect is shown presumably by scavenging of
the ROS by risperidone as an antioxidant.
PMID- 29937711
TI - The Role of Gaseous Molecules in Traumatic Brain Injury: An Updated Review.
AB - Traumatic brain injury (TBI) affects millions of people in China each year. TBI
has a high mortality and often times a serious prognosis. The causative
mechanisms of TBI during development and recovery from an injury remain vague,
leaving challenges for the medical community to provide treatment options that
improve prognosis and provide an optimal recovery. Biological gaseous molecules
including nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and
molecular hydrogen (H2) have been found to play critical roles in physiological
and pathological conditions in mammals. Accumulating evidence has found that
these gaseous molecules can execute neuroprotection in many central nervous
system (CNS) conditions due to their highly permeable properties allowing them to
enter the brain. Considering the complicated mechanisms and the serious prognosis
of TBI, effective and adequate therapeutic approaches are urgently needed. These
four gaseous molecules can be potential attractive therapeutic intervention on
TBI. In this review, we will present a comprehensive overview on the role of
these four biological gasses in the development of TBI and their potential
therapeutic applications.
PMID- 29937712
TI - Cortical Excitability and Interhemispheric Connectivity in Early Relapsing
Remitting Multiple Sclerosis Studied With TMS-EEG.
AB - Evoked potentials (EPs) are well established in clinical practice for diagnosis
and prognosis in multiple sclerosis (MS). However, their value is limited to the
assessment of their respective functional systems. Here, we used transcranial
magnetic stimulation (TMS) coupled with electroencephalography (TMS-EEG) to
investigate cortical excitability and spatiotemporal dynamics of TMS-evoked
neural activity in MS patients. Thirteen patients with early relapsing-remitting
MS (RRMS) with a median Expanded Disability Status Scale (EDSS) of 1.0 (range 0
2.5) and 16 age- and gender-matched healthy controls received single-pulse TMS of
left and right primary motor cortex (L-M1 and R-M1), respectively. Resting motor
threshold for L-M1 and R-M1 was increased in MS patients. Latencies and
amplitudes of N45, P70, N100, P180, and N280 TMS-evoked EEG potentials (TEPs)
were not different between groups, except a significantly increased amplitude of
the N280 TEP in the MS group, both for L-M1 and R-M1 stimulation.
Interhemispheric signal propagation (ISP), estimated from the area under the
curve of TEPs in the non-stimulated vs. stimulated M1, also did not differ
between groups. In summary, findings show that ISP and TEPs were preserved in
early-stage RRMS, except for an exaggerated N280 amplitude. Our findings indicate
that TMS-EEG is feasible in testing excitability and connectivity in cortical
neural networks in MS patients, complementary to conventional EPs. However,
relevance and pathophysiological correlates of the enhanced N280 will need
further study.
PMID- 29937713
TI - Cognitive Decline, Dementia, Alzheimer's Disease and Presbycusis: Examination of
the Possible Molecular Mechanism.
AB - The incidences of presbycusis and dementia are high among geriatric diseases.
Presbycusis is the general term applied to age-related hearing loss and can be
caused by many risk factors, such as noise exposure, smoking, medication,
hypertension, family history, and other factors. Mutation of mitochondrial DNA in
hair cells, spiral ganglion cells, and stria vascularis cells of the cochlea is
the basic mechanism of presbycusis. Dementia is a clinical syndrome that includes
the decline of cognitive and conscious states and is caused by many
neurodegenerative diseases, of which Alzheimer's disease (AD) is the most common.
The amyloid cascade hypothesis and tau hypothesis are the two major hypotheses
that describe the AD pathogenic mechanism. Recent studies have shown that
deposition of Abeta and hyperphosphorylation of the tau protein may cause
mitochondrial dysfunction. An increasing number of papers have reported that, on
one hand, the auditory system function in AD patients is damaged as their
cognitive ability declines and that, on the other hand, hearing loss may be a
risk factor for dementia and AD. However, the relationship between presbycusis
and AD is still unknown. By reviewing the relevant literature, we found that the
SIRT1-PGC1alpha pathway and LKB1 (or CaMKKbeta)-AMPK pathway may play a role in
the preservation of cerebral neuron function by taking part in the regulation of
mitochondrial function. Then vascular endothelial growth factor signal pathway is
activated to promote vascular angiogenesis and maintenance of the blood-brain
barrier integrity. Recently, experiments have also shown that their expression
levels are altered in both presbycusis and AD mouse models. Therefore, we propose
that exploring the specific molecular link between presbycusis and AD may provide
new ideas for their prevention and treatment.
PMID- 29937714
TI - Transcriptional Repression of p53 by PAX3 Contributes to Gliomagenesis and
Differentiation of Glioma Stem Cells.
AB - Although there are available therapies as surgery, chemotherapy and radiation,
glioblastoma (GBM) still has been considered as the most common and overwhelming
primary tumor of brain. In GBM, the brain glioma stem cells (BGSCs) were
identified and played a crucial role in resistance of GBM to conventional
therapies described above. PAX3 was previously identified by our group as a
diagnostic/prognostic marker and a therapeutic regulator in the therapy of GBM.
Here, we hypothesized PAX3/p53 axis promoted the process of differentiation,
regulating to the cancer stem cell properties, such as proliferation and
migration. The correlation between PAX3 and p53 in GBM were first clarified.
Immunofluorescence of p53 was shown activated following BGSCs differentiation. We
further identified that PAX3 might specifically bind to the promoter of p53 gene,
and transcriptionally repressed p53 expression. ChIP assay further confirmed that
PAX3/p53 axis regulated the differentiation process of BGSCs. Then, the function
of PAX3 in BGSCs were sequentially investigated in vitro and in vivo. Ectopic
PAX3 expression promoted BGSCs growth and migration while PAX3 knockdown
suppressed BGSCs growth, migration in vitro and in vivo. Similar to PAX3
overexpression, p53 inhibition also showed increase in growth and migration of
differentiated BGSCs. Regarding the functional interaction between PAX3 and p53,
PAX3 knockdown-mediated decrease in proliferation was partially rescued by p53
inhibition. Hypoxia significantly promoted the migration potential of BGSCs. In
addition, hypoxia inducible factor-1alpha (HIF-1alpha) might be a potential
upstream regulator of PAX3 in differentiated BGSCs under hypoxia. Our work may
provide a supplementary mechanism in regulation of the BGSCs differentiation and
their functions, which should provide novel therapeutic targets for GBM in
future.
PMID- 29937716
TI - MicroRNA-26b Regulates the Microglial Inflammatory Response in Hypoxia/Ischemia
and Affects the Development of Vascular Cognitive Impairment.
AB - Background: Microglia play an important role in the central nervous system as
immune cells and are often activated by post-ischemic injury. MicroRNAs are small
endogenous RNAs affecting many complex cellular biological functions that are
involved in neurodegenerative and cerebrovascular diseases. Previous studies have
shown that microRNA-26b (miR-26b) is downregulated in BV-2 cells exposed to
oxygen-glucose deprivation (OGD). Objective: This study aimed to investigate how
miR-26b regulates microglial activation and its neurotoxicity as well as the
effect of miR-26b on vascular cognitive impairment (VCI). Methods: Here, we used
PCR to detect the mRNA expression of miR-26b and cytokines, western blot for the
protein expression of cytokines, and the live/dead assay for neuronal apoptosis.
In addition, we employed a luciferase assay to identify the possible target genes
of miR-26b. Furthermore, we studied the effects of cerebral ischemia by bilateral
common carotid artery occlusion (BCCAO) in rats. We used staining to identify
neurons and microglia, and we tested cognitive function by the T-maze test.
Results: Our results showed that OGD activated microglia and increased the
expression of interleukin (IL)-6 and other cytokines. Similarly, BCCAO activated
microglia and increased the expression of IL-6 in the hippocampal CA1 area. We
further found that miR-26b decreased the number of activated microglia and
targeted IL-6. Moreover, miR-26b expression attenuated microglial activation,
inflammation, neurotoxicity and VCI. Conclusion: Our results suggested that miR
26b is involved in microglial activation and neurotoxicity in hypoxia/ischemia
via IL-6. Therefore, increasing miR-26b expression may improve cognitive
function.
PMID- 29937715
TI - Type 2 Diabetes Leads to Axon Initial Segment Shortening in db/db Mice.
AB - Cognitive and mood impairments are common central nervous system complications of
type 2 diabetes, although the neuronal mechanism(s) remains elusive. Previous
studies focused mainly on neuronal inputs such as altered synaptic plasticity.
Axon initial segment (AIS) is a specialized functional domain within neurons that
regulates neuronal outputs. Structural changes of AIS have been implicated as a
key pathophysiological event in various psychiatric and neurological disorders.
Here we evaluated the structural integrity of the AIS in brains of db/db mice, an
established animal model of type 2 diabetes associated with cognitive and mood
impairments. We assessed the AIS before (5 weeks of age) and after (10 weeks) the
development of type 2 diabetes, and after daily exercise treatment of diabetic
condition. We found that the development of type 2 diabetes is associated with
significant AIS shortening in both medial prefrontal cortex and hippocampus, as
evident by immunostaining of the AIS structural protein betaIV spectrin. AIS
shortening occurs in the absence of altered neuronal and AIS protein levels. We
found no change in nodes of Ranvier, another neuronal functional domain sharing a
molecular organization similar to the AIS. This is the first study to identify
AIS alteration in type 2 diabetes condition. Since AIS shortening is known to
lower neuronal excitability, our results may provide a new avenue for
understanding and treating cognitive and mood impairments in type 2 diabetes.
PMID- 29937717
TI - Direct Reprogramming of Adult Human Somatic Stem Cells Into Functional Neurons
Using Sox2, Ascl1, and Neurog2.
AB - Reprogramming of somatic cells into induced pluripotent stem cells (iPS) or
directly into cells from a different lineage, including neurons, has
revolutionized research in regenerative medicine in recent years. Mesenchymal
stem cells are good candidates for lineage reprogramming and autologous
transplantation, since they can be easily isolated from accessible sources in
adult humans, such as bone marrow and dental tissues. Here, we demonstrate that
expression of the transcription factors (TFs) SRY (sex determining region Y)-box
2 (Sox2), Mammalian achaete-scute homolog 1 (Ascl1), or Neurogenin 2 (Neurog2) is
sufficient for reprogramming human umbilical cord mesenchymal stem cells (hUCMSC)
into induced neurons (iNs). Furthermore, the combination of Sox2/Ascl1 or
Sox2/Neurog2 is sufficient to reprogram up to 50% of transfected hUCMSCs into iNs
showing electrical properties of mature neurons and establishing synaptic
contacts with co-culture primary neurons. Finally, we show evidence supporting
the notion that different combinations of TFs (Sox2/Ascl1 and Sox2/Neurog2) may
induce multiple and overlapping neuronal phenotypes in lineage-reprogrammed iNs,
suggesting that neuronal fate is determined by a combination of signals involving
the TFs used for reprogramming but also the internal state of the converted cell.
Altogether, the data presented here contribute to the advancement of techniques
aiming at obtaining specific neuronal phenotypes from lineage-converted human
somatic cells to treat neurological disorders.
PMID- 29937718
TI - Commentary: Respiration-Entrained Brain Rhythms Are Global but Often Overlooked.
PMID- 29937720
TI - Novel Insights Into the Mechanisms of Abdominal Pain in Obstructive Bowel
Disorders.
AB - Obstructive bowel disorders (OBD) are characterized by lumen distention due to
mechanical or functional obstruction in the gut. Abdominal pain is one of the
main symptoms in OBD. In this article, we aim to critically review the potential
mechanisms for acute and chronic pain in bowel obstruction (BO). While clustered
contractions and associated increase of intraluminal pressure may account for
colicky pain in simple obstruction, ischemia may be involved in acute pain in
severe conditions such as closed loop obstruction. Recent preclinical studies
discovered that visceral sensitivity is increased in BO, and visceral
hypersensitivity may underlie the mechanisms of chronic abdominal pain in BO.
Mounting evidence suggests that lumen distension, as a circumferential mechanical
stretch, alters gene expression (mechano-transcription) in the distended bowel,
and mechano-transcription of nociceptive and inflammatory mediators plays a
critical role in the development of visceral hypersensitivity in BO. Mechano
transcription of nerve growth factor (NGF) in gut smooth muscle cells is found to
increase voltage-gated Na+ channel (Nav) activity of the primary sensory neurons
by up-regulating expression of TTX-resistant Nav1.8, whereas mechanical stretch
induced brain-derived neurotrophic factor (BDNF) reduces Kv currents especially A
type (IA) currents by down-regulating expression of specific IA subtypes such as
Kv1.4. The NGF and BDNF mediated changes in gene expression and channel functions
in the primary sensory neurons may constitute the main mechanisms of visceral
hypersensitivity in OBD. In addition, mechanical stretch-induced COX-2 and other
inflammatory mediators in the gut may also contribute to abdominal pain by
activating and sensitizing nociceptors.
PMID- 29937721
TI - Altered Light Conditions Contribute to Abnormalities in Emotion and Cognition
Through HINT1 Dysfunction in C57BL/6 Mice.
AB - In recent years, the environmental impact of artificial light at night has been a
rapidly growing global problem, affecting 99% of the population in the US and
Europe, and 62% of the world population. The present study utilized a mouse model
exposed to long-term artificial light and light deprivation to explore the impact
of these conditions on emotion and cognition. Based on the potential links
between histidine triad nucleotide binding protein 1 (HINT1) and mood disorders,
we also examined the expression of HINT1 and related apoptosis factors in the
suprachiasmatic nucleus (SCN), prefrontal cortex (PFC), nucleus accumbens (NAc)
and hippocampus (Hip). Mice exposed to constant light (CL) exhibited depressive-
and anxiety-like behaviors, as well as impaired spatial memory, as demonstrated
by an increased immobility time in the tail suspension and forced swimming tests,
less entries and time spent in the open arms of elevated plus-maze, and less
platform site crossings and time spent in the target quadrant in the Morris water
maze (MWM). The effects of constant darkness (CD) partially coincided with long
term illumination, except that mice in the CD group failed to show anxiety-like
behaviors. Furthermore, HINT1 was upregulated in four encephalic regions,
indicating that HINT1 may be involved in mood disorders and cognitive impairments
due to altered light exposure. The apoptosis-related proteins, BAX and BCL-2,
showed the opposite expression pattern, reflecting an activated apoptotic
pathway. These findings suggest that exposure to CL and/or darkness can induce
significant changes in affective and cognitive responses, possibly through HINT1
induced activation of apoptotic pathways.
PMID- 29937722
TI - Modeling Current Sources for Neural Stimulation in COMSOL.
AB - Background: Computational modeling provides an important toolset for designing
and analyzing neural stimulation devices to treat neurological disorders and
diseases. Modeling enables efficient exploration of large parameter spaces, where
preclinical and clinical studies would be infeasible. Current commercial finite
element method software packages enable straightforward calculation of the
potential distributions, but it is not always clear how to implement boundary
conditions to appropriately represent metal stimulating electrodes. By
quantifying the effects of different electrode representations on activation
thresholds for model axons, we provide recommendations for accurate and efficient
modeling of neural stimulating electrodes. Methods: We quantified the effects of
different representations of current sources for neural stimulation in COMSOL
Multiphysics for monopolar, bipolar, and multipolar electrode designs. Results:
We recommend modeling each electrode contact as a thin platinum domain, modeling
the electrode substrate with the conductivity of silicone, and either using a
point current source in the center of each electrode contact or using a boundary
current source. Alternatively, to avoid possible numerical instabilities
associated with a large range of conductivity values (i.e., platinum and
silicone) and to eliminate the small mesh elements required for thin electrode
contacts, the electrode substrate can be assigned the conductivity of platinum by
using insulating boundaries between the substrate and surrounding medium, and
within the substrate to isolate the contacts from each other. When modeling more
than one contact, we recommend using superposition by solving the model once for
each contact, leaving inactive contacts floating, and superposing the resulting
potentials. We computed comparable errors in activation thresholds across the
different implementations in a simplified model (electrode in a homogeneous,
isotropic medium), and in realistic models of rat spinal cord stimulation (SCS)
and human deep brain stimulation, indicating that the recommended approaches are
applicable to different stimulation targets.
PMID- 29937719
TI - The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression-The
Glucocorticoid Deficit Hypothesis.
AB - This review argues for a central role of the lateral hypothalamus in those
deviant forms of aggression, which result from chronic glucocorticoid deficiency.
Currently, this nucleus is considered a key region of the mechanisms that control
predatory aggression. However, recent findings demonstrate that it is strongly
activated by aggression in subjects with a chronically downregulated hypothalamus
pituitary-adrenocortical (HPA) axis; moreover, this activation is causally
involved in the emergence of violent aggression. The review has two parts. In the
first part, we review human findings demonstrating that under certain conditions,
strong stressors downregulate the HPA-axis on the long run, and that the
resulting glucocorticoid deficiency is associated with violent aggression
including aggressive delinquency and aggression-related psychopathologies. The
second part addresses neural mechanisms in animals. We show that the experimental
downregulation of HPA-axis function elicits violent aggression in rodents, and
the activation of the brain circuitry that originally subserves predatory
aggression accompanies this change. The lateral hypothalamus is not only an
integral part of this circuitry, but can elicit deviant and violent forms of
aggression. Finally, we formulate a hypothesis on the pathway that connects
unfavorable social conditions to violent aggression via the neural circuitry that
includes the lateral hypothalamus.
PMID- 29937723
TI - Toward Rigorous Parameterization of Underconstrained Neural Network Models
Through Interactive Visualization and Steering of Connectivity Generation.
AB - Simulation models in many scientific fields can have non-unique solutions or
unique solutions which can be difficult to find. Moreover, in evolving systems,
unique final state solutions can be reached by multiple different trajectories.
Neuroscience is no exception. Often, neural network models are subject to
parameter fitting to obtain desirable output comparable to experimental data.
Parameter fitting without sufficient constraints and a systematic exploration of
the possible solution space can lead to conclusions valid only around local
minima or around non-minima. To address this issue, we have developed an
interactive tool for visualizing and steering parameters in neural network
simulation models. In this work, we focus particularly on connectivity
generation, since finding suitable connectivity configurations for neural network
models constitutes a complex parameter search scenario. The development of the
tool has been guided by several use cases-the tool allows researchers to steer
the parameters of the connectivity generation during the simulation, thus quickly
growing networks composed of multiple populations with a targeted mean activity.
The flexibility of the software allows scientists to explore other connectivity
and neuron variables apart from the ones presented as use cases. With this tool,
we enable an interactive exploration of parameter spaces and a better
understanding of neural network models and grapple with the crucial problem of
non-unique network solutions and trajectories. In addition, we observe a
reduction in turn around times for the assessment of these models, due to
interactive visualization while the simulation is computed.
PMID- 29937724
TI - Affordance Equivalences in Robotics: A Formalism.
AB - Automatic knowledge grounding is still an open problem in cognitive robotics.
Recent research in developmental robotics suggests that a robot's interaction
with its environment is a valuable source for collecting such knowledge about the
effects of robot's actions. A useful concept for this process is that of an
affordance, defined as a relationship between an actor, an action performed by
this actor, an object on which the action is performed, and the resulting effect.
This paper proposes a formalism for defining and identifying affordance
equivalence. By comparing the elements of two affordances, we can identify
equivalences between affordances, and thus acquire grounded knowledge for the
robot. This is useful when changes occur in the set of actions or objects
available to the robot, allowing to find alternative paths to reach goals. In the
experimental validation phase we verify if the recorded interaction data is
coherent with the identified affordance equivalences. This is done by querying a
Bayesian Network that serves as container for the collected interaction data, and
verifying that both affordances considered equivalent yield the same effect with
a high probability.
PMID- 29937725
TI - Hebbian Plasticity in CPG Controllers Facilitates Self-Synchronization for Human
Robot Handshaking.
AB - It is well-known that human social interactions generate synchrony phenomena
which are often unconscious. If the interaction between individuals is based on
rhythmic movements, synchronized and coordinated movements will emerge from the
social synchrony. This paper proposes a plausible model of plastic neural
controllers that allows the emergence of synchronized movements in physical and
rhythmical interactions. The controller is designed with central pattern
generators (CPG) based on rhythmic Rowat-Selverston neurons endowed with neuronal
and synaptic Hebbian plasticity. To demonstrate the interest of the proposed
model, the case of handshaking is considered because it is a very common, both
physically and socially, but also, a very complex act in the point of view of
robotics, neuroscience and psychology. Plastic CPGs controllers are implemented
in the joints of a simulated robotic arm that has to learn the frequency and
amplitude of an external force applied to its effector, thus reproducing the act
of handshaking with a human. Results show that the neural and synaptic Hebbian
plasticity are working together leading to a natural and autonomous
synchronization between the arm and the external force even if the frequency is
changing during the movement. Moreover, a power consumption analysis shows that,
by offering emergence of synchronized and coordinated movements, the plasticity
mechanisms lead to a significant decrease in the energy spend by the robot
actuators thus generating a more adaptive and natural human/robot handshake.
PMID- 29937726
TI - Extrasynaptic Neurotransmission Mediated by Exocytosis and Diffusive Release of
Transmitter Substances.
AB - This review article deals with the mechanisms of extrasynaptic release of
transmitter substances, namely the release from the soma, axon and dendrites in
the absence of postsynaptic counterparts. Extrasynaptic release occurs by
exocytosis or diffusion. Spillover from the synaptic cleft also contributes to
extrasynaptic neurotransmission. Here, we first describe two well-known examples
of exocytosis from the neuronal soma, which may release copious amounts of
transmitter for up to hundreds of seconds after electrical stimulation. The
mechanisms for somatic exocytosis of the low molecular weight transmitter
serotonin, and the peptides oxytocin and vasopressin have been studied in detail.
Serotonin release from leech neurons and oxytocin and vasopressin from rodent
neurons have a common multi-step mechanism, which is completely different from
that for exocytosis from presynaptic endings. Most transmitters and peptides
released extrasynaptically seem to follow this same mechanism. Extrasynaptic
exocytosis may occur onto glial cells, which act as intermediaries for long-term
and long-distance transmission. The second part of this review article focuses on
the release upon synthesis of the representative diffusible molecules nitric
oxide (NO) and endocannabinoids. Diffusible molecules are synthesized "on demand"
from postsynaptic terminals in response to electrical activity and intracellular
calcium elevations. Their effects include the retrograde modulation of
presynaptic electrical activity and transmitter release. Extrasynaptic
neurotransmission is well exemplified in the retina. Light-evoked extrasynaptic
communication sets the gain for visual responses and integrates the activity of
neurons, glia and blood vessels. Understanding how extrasynaptic communication
changes the function of hard-wired circuits has become fundamental to understand
the function of the nervous system.
PMID- 29937728
TI - Lower Expression of Ndfip1 Is Associated With Alzheimer Disease Pathogenesis
Through Decreasing DMT1 Degradation and Increasing Iron Influx.
AB - We have previously reported that high expression of divalent metal transporter 1
(DMT1) plays a crucial role in iron dyshomeostasis and beta-amyloid (Abeta)
peptide generation in the brain of Alzheimer's disease (AD). Recent studies have
shown that Nedd4 family interacting protein 1 (Ndfip1) can degrade DMT1 through
ubiquitination pathway and reduce the accumulation of intracellular iron. The
present study aims to evaluate whether Ndfip1 is involved in AD pathogenesis
through mediating DMT1 degradation and iron metabolism. beta-amyloid precursor
protein/presenilin 1 (APP/PS1) transgenic mouse and Ndfip1 transfected SH-SY5Y
cells were used in this study. Immunohistochemistry and Western blot were
performed to examine the distribution and expression levels of Ndfip1 and DMT1.
In addition, ELISA and calcein fluorescence were carried out for analyzing the
levels of Abeta peptide and iron influx, respectively. The results showed that
Ndfip1 immunoreactivity was decreased in the cortex and hippocampus of APP/PS1
mice, compared with wild type (WT) controls. Colocalization of Ndfip1 and Abeta
within senile plaques could be observed. Immunoblot analyses showed that low
expression of Ndfip1 and high expression of DMT1 proteins were detected in
APP/PS1 mouse brain, compared with age-matched WT animals. Overexpression of
Ndfip1 down-regulated DMT1 expression, and reduced iron influx and Abeta
secretion in SH-SY5Y cells. Further, overexpressed Ndfip1 significantly
attenuated iron-induced cell damage in Ndfip1 transfected cells. The present
study suggests that lower expression of Ndfip1 might be associated with the
pathogenesis of AD, through decreasing DMT1 degradation and increasing iron
accumulation in the brain.
PMID- 29937727
TI - Modeling Neurological Diseases With Human Brain Organoids.
AB - The complexity and delicacy of human brain make it challenging to recapitulate
its development, function and disorders. Brain organoids derived from human
pluripotent stem cells (PSCs) provide a new tool to model both normal and
pathological human brain, and greatly enhance our ability to study brain biology
and diseases. Currently, human brain organoids are increasingly used in modeling
neurological disorders and relative therapeutic discovery. This review article
focuses on recent advances in human brain organoid system and its application in
disease modeling. It also discusses the limitations and future perspective of
human brain organoids in modeling neurological diseases.
PMID- 29937729
TI - Chemical Analysis and Multi-Component Determination in Chinese Medicine
Preparation Bupi Yishen Formula Using Ultra-High Performance Liquid
Chromatography With Linear Ion Trap-Orbitrap Mass Spectrometry and Triple
Quadrupole Tandem Mass Spectrometry.
AB - Bupi Yishen Formula (BYF), a Chinese medicine preparation, has been clinically
applied for the recovery of chronic kidney disease and for delaying its progress.
Nevertheless, the chemical components in BYF have yet to be fully clarified.
Ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass
spectrometry (UHPLC-LTQ-Orbitrap-MSn) and triple-quadrupole tandem mass
spectrometry (UHPLC-TQ-MS/MS) methods were developed for qualitative chemical
profiling and multi-components quantitative analysis in BYF. The chromatographic
separation was performed on a Phenomenex Kinetex C18 column (2.1 * 100 mm i.d.,
1.7 MUm) using gradient elution of water (A) and acetonitrile (B) both containing
0.1% formic acid. Eighty-six compounds, including flavones, saponins, phenolic
acids, and other compounds were authenticated or temporarily deduced according to
their retention behaviors, mass mensuration, and characteristic fragment ions
with those elucidated reference substances or literatures. Among the herbal
medicinal materials of the formula, Astragali Radix, Codonopsis Radix, Salviae
Miltiorrhizae Radix Rhizoma, and Polygoni Multiflori Radix Praeparata contributed
to the bulk of the dissolved metabolites of the formula extraction. In addition,
seven analytes were simultaneously determined by UHPLC-TQ-MS/MS, which was
validated and has managed to determine major components in BYF. The study
indicated that the established qualitative and quantitative methods would be
potent and dependable analytical tools for characterizing multi-constituent in
complex prescriptions decoction and provided a basis for the evaluation of
bioactive components in BYF.
PMID- 29937730
TI - Applying a Global Sensitivity Analysis Workflow to Improve the Computational
Efficiencies in Physiologically-Based Pharmacokinetic Modeling.
AB - Traditionally, the solution to reduce parameter dimensionality in a
physiologically-based pharmacokinetic (PBPK) model is through expert judgment.
However, this approach may lead to bias in parameter estimates and model
predictions if important parameters are fixed at uncertain or inappropriate
values. The purpose of this study was to explore the application of global
sensitivity analysis (GSA) to ascertain which parameters in the PBPK model are
non-influential, and therefore can be assigned fixed values in Bayesian parameter
estimation with minimal bias. We compared the elementary effect-based Morris
method and three variance-based Sobol indices in their ability to distinguish
"influential" parameters to be estimated and "non-influential" parameters to be
fixed. We illustrated this approach using a published human PBPK model for
acetaminophen (APAP) and its two primary metabolites APAP-glucuronide and APAP
sulfate. We first applied GSA to the original published model, comparing Bayesian
model calibration results using all the 21 originally calibrated model parameters
(OMP, determined by "expert judgment"-based approach) vs. the subset of original
influential parameters (OIP, determined by GSA from the OMP). We then applied GSA
to all the PBPK parameters, including those fixed in the published model,
comparing the model calibration results using this full set of 58 model
parameters (FMP) vs. the full set influential parameters (FIP, determined by GSA
from FMP). We also examined the impact of different cut-off points to distinguish
the influential and non-influential parameters. We found that Sobol indices
calculated by eFAST provided the best combination of reliability (consistency
with other variance-based methods) and efficiency (lowest computational cost to
achieve convergence) in identifying influential parameters. We identified several
originally calibrated parameters that were not influential, and could be fixed to
improve computational efficiency without discernable changes in prediction
accuracy or precision. We further found six previously fixed parameters that were
actually influential to the model predictions. Adding these additional
influential parameters improved the model performance beyond that of the original
publication while maintaining similar computational efficiency. We conclude that
GSA provides an objective, transparent, and reproducible approach to improve the
performance and computational efficiency of PBPK models.
PMID- 29937731
TI - Long-Term Intravitreal Ranibizumab as a Potential Additional Risk Factor for
Neurodegeneration in Parkinson's Disease: A Case Report.
AB - In November 2012, a 72-year old patient was diagnosed with left eye wet age
related macular degeneration. The patient received three monthly intravitreal
injections of ranibizumab, with complete resolution of retinal hemorrhage and
edema and reinstatement of visual acuity. In May 2015, symptomatic relapse was
detected. The patient was again treated with intravitreal ranibizumab, with
overall six injections till the end of February 2016. In May 2016, the patient
complained of left hand resting tremor, bradykinesia, and postural rigidity of
head and trunk. A diagnosis of clinically established PD was made based on new
criteria of the Movement Disorders Society. Single Photon Emission Computerized
Tomography of the Dopamine Transporter with (123I) ioflupane documented a low
Dopamine Transporter (DAT) uptake mostly in the right striatum. Due to the
documented protective role of vascular endothelial growth factor (VEGF) on the
dopaminergic neurons, intensive intravitreal injections of the anti-VEGF agent
ranibizumab may have played as an additional risk factor accelerating the
neurodegeneration process related to PD and the onset of the related clinical
signs and symptoms.
PMID- 29937733
TI - Editorial: Safety Pharmacology - Risk Assessment QT Interval Prolongation and
Beyond.
PMID- 29937732
TI - The Effects of Moderate Physical Exercise on Adult Cognition: A Systematic
Review.
AB - Background: Physical exercise is a systematic sequence of movements executed with
a predefined purpose. This muscular activity impacts not only on circulatory
adaptations, but also neuronal integration with the potential to influence
cognition. The aim of this review was to determine whether the literature
supports the idea that physical exercise promotes cognitive benefits in healthy
adults. Methods: A systematic search for relevant articles was performed
according to the Preferred Reporting Items for Systematic Review and Meta
Analysis criteria using available databases (PubMed, LILACS, Scopus, Web of
Science, The Cochrane Library, OpenGrey, Google Scholar and CENTRAL). The search
terms included "humans" or "adults" or "cognition" or "awareness" or "cognitive
dissonance" or "cognitive reserve" or "comprehension" or "consciousness" and
"motor activity" or "exercise" or "physical fitness," and not "aged" or "nervous
system diseases," with the purpose of finding associations between moderate
physical exercise and cognition. A methodological quality and risk of bias unit
assessed the eligibility of articles. Results: A total of 7179 articles were
identified. Following review and quality assessment, three articles were
identified to fulfill the inclusion criteria. An association between moderate
physical exercise and cognition was observed. Improvements in cognitive
parameters such as reduced simple reaction time, improved response precision and
working memory were identified among the included articles. Conclusion: This
systematic review found that moderate physical exercise improves cognition.
PMID- 29937734
TI - MiRNA-155 Regulates the Th17/Treg Ratio by Targeting SOCS1 in Severe Acute
Pancreatitis.
AB - Acute pancreatitis (AP) is a serious condition associated with intestinal barrier
disruption or inflammation of the pancreatic tissue. Specific microRNAs are
involved in the pathogenesis of AP, during which IL-17-producing CD4+ T helper
(Th17) cells accumulate in the pancreas. In this study, significantly increased
levels of miR-155 were detected in clinical samples from patients with AP, and
overexpression of miR-155 correlated with severe AP (SAP). To identify the effect
of miR-155 on T cell differentiation, we isolated CD4+ T lymphocytes and in vitro
experiments showed that inhibition of miR-155 significantly reversed the stress
induced increase in the Th17/Treg ratio. The results also showed that miR-155
increased the Th17-mediated inflammatory response by targeting SOCS1. The
interaction between miR-155 and the 3'-UTR of SOCS1 was confirmed by a dual
luciferase reporter assay and RT-PCR. Experimental AP of varying severity was
induced in BALB/c mice by caerulein hyperstimulation and miR-155 expression was
found to increase with disease progression. Inhibition of miR-155 expression
significantly improved the pathology of the pancreas. We also observed
downregulation of expression of inflammatory factors, IL-17, SOCS1 and
phosphorylated STAT1 after miR-155 inhibition. In summary, miR-155 regulates the
Th17/Treg ratio by targeting SOCS1, most probably via direct binding to its 3'
UTR region, indicating that this microRNA may be a potential biomarker and/or
therapeutic target for AP.
PMID- 29937735
TI - Identification of Boolean Network Models From Time Series Data Incorporating
Prior Knowledge.
AB - Motivation: Mathematical models take an important place in science and
engineering. A model can help scientists to explain dynamic behavior of a system
and to understand the functionality of system components. Since length of a time
series and number of replicates is limited by the cost of experiments, Boolean
networks as a structurally simple and parameter-free logical model for gene
regulatory networks have attracted interests of many scientists. In order to fit
into the biological contexts and to lower the data requirements, biological prior
knowledge is taken into consideration during the inference procedure. In the
literature, the existing identification approaches can only deal with a subset of
possible types of prior knowledge. Results: We propose a new approach to identify
Boolean networks from time series data incorporating prior knowledge, such as
partial network structure, canalizing property, positive and negative unateness.
Using vector form of Boolean variables and applying a generalized matrix
multiplication called the semi-tensor product (STP), each Boolean function can be
equivalently converted into a matrix expression. Based on this, the
identification problem is reformulated as an integer linear programming problem
to reveal the system matrix of Boolean model in a computationally efficient way,
whose dynamics are consistent with the important dynamics captured in the data.
By using prior knowledge the number of candidate functions can be reduced during
the inference. Hence, identification incorporating prior knowledge is especially
suitable for the case of small size time series data and data without sufficient
stimuli. The proposed approach is illustrated with the help of a biological model
of the network of oxidative stress response. Conclusions: The combination of
efficient reformulation of the identification problem with the possibility to
incorporate various types of prior knowledge enables the application of
computational model inference to systems with limited amount of time series data.
The general applicability of this methodological approach makes it suitable for a
variety of biological systems and of general interest for biological and medical
research.
PMID- 29937736
TI - Red Blood Cell Homeostasis: Mechanisms and Effects of Microvesicle Generation in
Health and Disease.
AB - Red blood cells (RBCs) generate microvesicles to remove damaged cell constituents
such as oxidized hemoglobin and damaged membrane constituents, and thereby
prolong their lifespan. Damage to hemoglobin, in combination with altered
phosphorylation of membrane proteins such as band 3, lead to a weakening of the
binding between the lipid bilayer and the cytoskeleton, and thereby to membrane
budding and microparticle shedding. Microvesicle generation is disturbed in
patients with RBC-centered diseases, such as sickle cell disease, glucose 6
phosphate dehydrogenase deficiency, spherocytosis or malaria. A disturbance of
the membrane-cytoskeleton interaction is likely to be the main underlying
mechanism, as is supported by data obtained from RBCs stored in blood bank
conditions. A detailed proteomic, lipidomic and immunogenic comparison of
microvesicles derived from different sources is essential in the identification
of the processes that trigger vesicle generation. The contribution of RBC-derived
microvesicles to inflammation, thrombosis and autoimmune reactions emphasizes the
need for a better understanding of the mechanisms and consequences of
microvesicle generation.
PMID- 29937737
TI - Mangifera indica L. Leaf Extract in Combination With Luteolin or Quercetin
Enhances VO2peak and Peak Power Output, and Preserves Skeletal Muscle Function
During Ischemia-Reperfusion in Humans.
AB - It remains unknown whether polyphenols such as luteolin (Lut), mangiferin and
quercetin (Q) have ergogenic effects during repeated all-out prolonged sprints.
Here we tested the effect of Mangifera indica L. leaf extract (MLE) rich in
mangiferin (Zynamite(r)) administered with either quercetin (Q) and tiger nut
extract (TNE), or with luteolin (Lut) on sprint performance and recovery from
ischemia-reperfusion. Thirty young volunteers were randomly assigned to three
treatments 48 h before exercise. Treatment A: placebo (500 mg of
maltodextrin/day); B: 140 mg of MLE (60% mangiferin) and 50 mg of Lut/day; and C:
140 mg of MLE, 600 mg of Q and 350 mg of TNE/day. After warm-up, subjects
performed two 30 s Wingate tests and a 60 s all-out sprint interspaced by 4 min
recovery periods. At the end of the 60 s sprint the circulation of both legs was
instantaneously occluded for 20 s. Then, the circulation was re-opened and a 15 s
sprint performed, followed by 10 s recovery with open circulation, and another 15
s final sprint. MLE supplements enhanced peak (Wpeak) and mean (Wmean) power
output by 5.0-7.0% (P < 0.01). After ischemia, MLE+Q+TNE increased Wpeak by 19.4
and 10.2% compared with the placebo (P < 0.001) and MLE+Lut (P < 0.05),
respectively. MLE+Q+TNE increased Wmean post-ischemia by 11.2 and 6.7% compared
with the placebo (P < 0.001) and MLE+Lut (P = 0.012). Mean VO2 during the sprints
was unchanged, suggesting increased efficiency or recruitment of the anaerobic
capacity after MLE ingestion. In women, peak VO2 during the repeated sprints was
5.8% greater after the administration of MLE, coinciding with better brain
oxygenation. MLE attenuated the metaboreflex hyperpneic response post-ischemia,
may have improved O2 extraction by the Vastus Lateralis (MLE+Q+TNE vs. placebo, P
= 0.056), and reduced pain during ischemia (P = 0.068). Blood lactate, acid-base
balance, and plasma electrolytes responses were not altered by the supplements.
In conclusion, a MLE extract rich in mangiferin combined with either quercetin
and tiger nut extract or luteolin exerts a remarkable ergogenic effect,
increasing muscle power in fatigued subjects and enhancing peak VO2 and brain
oxygenation in women during prolonged sprinting. Importantly, the combination of
MLE+Q+TNE improves skeletal muscle contractile function during
ischemia/reperfusion.
PMID- 29937738
TI - Reliability, Convergent Validity and Time Invariance of Default Mode Network
Deviations in Early Adult Major Depressive Disorder.
AB - There is substantial variability across studies of default mode network (DMN)
connectivity in major depressive disorder, and reliability and time-invariance
are not reported. This study evaluates whether DMN dysconnectivity in remitted
depression (rMDD) is reliable over time and symptom-independent, and explores
convergent relationships with cognitive features of depression. A longitudinal
study was conducted with 82 young adults free of psychotropic medications (47
rMDD, 35 healthy controls) who completed clinical structured interviews,
neuropsychological assessments, and 2 resting-state fMRI scans across 2 study
sites. Functional connectivity analyses from bilateral posterior cingulate and
anterior hippocampal formation seeds in DMN were conducted at both time points
within a repeated-measures analysis of variance to compare groups and evaluate
reliability of group-level connectivity findings. Eleven hyper- (from posterior
cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD
were obtained with moderate to adequate reliability in all but one cluster (ICC's
range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a
principle component analysis (5 components obtained) to explore these
connectivity components, and were then correlated with cognitive features
(rumination, cognitive control, learning and memory, and explicit emotion
identification). At the exploratory level, for convergent validity, components
consisting of posterior cingulate with cognitive control network
hyperconnectivity in rMDD were related to cognitive control (inverse) and
rumination (positive). Components consisting of anterior hippocampal formation
with social emotional network and DMN hypoconnectivity were related to memory
(inverse) and happy emotion identification (positive). Thus, time-invariant DMN
connectivity differences exist early in the lifespan course of depression and are
reliable. The nuanced results suggest a ventral within-network hypoconnectivity
associated with poor memory and a dorsal cross-network hyperconnectivity linked
to poorer cognitive control and elevated rumination. Study of early course
remitted depression with attention to reliability and symptom independence could
lead to more readily translatable clinical assessment tools for biomarkers.
PMID- 29937739
TI - Community-Based Psychosocial Treatment Has an Impact on Social Processing and
Functional Outcome in Schizophrenia.
AB - Schizophrenic patients have serious impairments in social cognition, which often
persists after significant reduction in clinical symptoms. Community-based
psychosocial treatments aim to recover social functioning for mentally ill
individuals. Our aim was to examine prospective changes in social cognition and
functional outcomes in two groups of schizophrenic patients involved in two forms
of community-based psychosocial treatments namely case management (CM) and
community-based club (CC) compared to a matched, treatment as usual (TAU) group
of patients. We hypothesized that CC and CM groups would exhibit better
functional and social cognitive outcomes after a 6-month long psychosocial
treatment period. Seventy-five patients participated either in CC, CM or TAU.
Both CC and CM took part in community-based psychosocial treatment programs
including trainings, such as communication and assertiveness trainings. In
addition, CC provided group therapeutic treatments and a continuously available
day care where patients had the possibility to participate in various social
interactions. All participants were in remission, and on maintenance
antipsychotic treatment. Participants were assessed on all study variables at two
time points: baseline and after 6 months with a battery of questionnaires that
examined affective face perception, affective prosody perception, pragmatic
language comprehension and ToM. Our results showed that functional outcomes
improved significantly in the CC as well as in the CM groups, in contrast to the
TAU group. While analyzing summary scores of social cognition, it was found that
only the CC group increased its performance in social cognition. In addition, a
significant between-group difference in social cognitive function was found after
6 months between the three groups, with the CC group performing best. When
investigating associations between changes in social cognition and changes in
functional outcomes during a 6-month long treatment period, we found significant
correlations between the two variables both in the CC and in the CM groups. Based
on our results, we suggest that a rich interpersonal network and social support
have highly beneficial effects on social cognition and we would like to emphasize
the necessity of offering community-based psychosocial treatments beside
antipsychotic medications as early as possible as a crucial part of the complex
therapy of schizophrenia.
PMID- 29937740
TI - The Detection of Malingering: A New Tool to Identify Made-Up Depression.
AB - Major depression is a high-prevalence mental disease with major socio-economic
impact, for both the direct and the indirect costs. Major depression symptoms can
be faked or exaggerated in order to obtain economic compensation from insurance
companies. Critically, depression is potentially easily malingered, as the
symptoms that characterize this psychiatric disorder are not difficult to
emulate. Although some tools to assess malingering of psychiatric conditions are
already available, they are principally based on self-reporting and are thus
easily faked. In this paper, we propose a new method to automatically detect the
simulation of depression, which is based on the analysis of mouse movements while
the patient is engaged in a double-choice computerized task, responding to simple
and complex questions about depressive symptoms. This tool clearly has a key
advantage over the other tools: the kinematic movement is not consciously
controllable by the subjects, and thus it is almost impossible to deceive. Two
groups of subjects were recruited for the study. The first one, which was used to
train different machine-learning algorithms, comprises 60 subjects (20 depressed
patients and 40 healthy volunteers); the second one, which was used to test the
machine-learning models, comprises 27 subjects (9 depressed patients and 18
healthy volunteers). In both groups, the healthy volunteers were randomly
assigned to the liars and truth-tellers group. Machine-learning models were
trained on mouse dynamics features, which were collected during the subject
response, and on the number of symptoms reported by participants. Statistical
results demonstrated that individuals that malingered depression reported a
higher number of depressive and non-depressive symptoms than depressed
participants, whereas individuals suffering from depression took more time to
perform the mouse-based tasks compared to both truth-tellers and liars. Machine
learning models reached a classification accuracy up to 96% in distinguishing
liars from depressed patients and truth-tellers. Despite this, the data are not
conclusive, as the accuracy of the algorithm has not been compared with the
accuracy of the clinicians; this study presents a possible useful method that is
worth further investigation.
PMID- 29937741
TI - The Strategic Meaning of CBCA Criteria From the Perspective of Deceivers.
AB - In 2014, Volbert and Steller introduced a revised model of Criteria-Based Content
Analysis (CBCA) that grouped a modified set of content criteria in closer
reference to their assumed latent processes, resulting in three dimensions of
memory-related, script-deviant and strategy-based criteria. In this model, it is
assumed that deceivers try to integrate memory-related criteria-but will not be
as good as truth tellers in achieving this-whereas out of strategic
considerations they will avoid the expression of the other criteria. The aim of
the current study was to test this assumption. A vignette was presented via an
online-questionnaire to inquire how participants (n = 135) rate the strategic
value of CBCA criteria on a five-point scale. One-sample t-tests showed that
participants attribute positive strategic value to most memory-related criteria
and negative value to the remaining criteria, except for the criteria self
deprecation and pardoning the perpetrator. Overall, our results corroborated the
model's suitability in distinguishing different groups of criteria-some which
liars are inclined to integrate and others which liars intend to avoid-and in
this way provide useful hints for forensic practitioners in appraising the
criteria' diagnostic value.
PMID- 29937742
TI - Age-Related Developmental and Individual Differences in the Influence of Social
and Non-social Distractors on Cognitive Performance.
AB - This study sought to examine age-related differences in the influences of social
(neutral, emotional faces) and non-social/non-emotional (shapes) distractor
stimuli in children, adolescents, and adults. To assess the degree to which
distractor, or task-irrelevant, stimuli of varying social and emotional salience
interfere with cognitive performance, children (N = 12; 8-12y), adolescents (N =
17; 13-17y), and adults (N = 17; 18-52y) completed the Emotional Identification
and Dynamic Faces (EIDF) task. This task included three types of dynamically
changing distractors: (1) neutral-social (neutral face changing into another
face); (2) emotional-social (face changing from 0% emotional to 100% emotional);
and (3) non-social/non-emotional (shapes changing from small to large) to index
the influence of task-irrelevant social and emotional information on cognition.
Results yielded no age-related differences in accuracy but showed an age-related
linear reduction in correct reaction times across distractor conditions. An age
related effect in interference was observed, such that children and adults showed
slower response times on correct trials with socially-salient distractors;
whereas adolescents exhibited faster responses on trials with distractors that
included faces rather than shapes. A secondary study goal was to explore
individual differences in cognitive interference. Results suggested that
regardless of age, low trait anxiety and high effortful control were associated
with interference to angry faces. Implications for developmental differences in
affective processing, notably the importance of considering the contexts in which
purportedly irrelevant social and emotional information might impair, vs. improve
cognitive control, are discussed.
PMID- 29937743
TI - P-Value, Confidence Intervals, and Statistical Inference: A New Dataset of
Misinterpretation.
PMID- 29937744
TI - Methods for Evaluating Emotions Evoked by Food Experiences: A Literature Review.
AB - Besides sensory characteristics of food, food-evoked emotion is a crucial factor
in predicting consumer's food preference and therefore in developing new
products. Many measures have been developed to assess food-evoked emotions. The
aim of this literature review is (i) to give an exhaustive overview of measures
used in current research and (ii) to categorize these methods along measurement
level (physiological, behavioral, and cognitive) and emotional processing level
(unconscious sensory, perceptual/early cognitive, and conscious/decision making)
level. This 3 * 3 categorization may help researchers to compile a set of
complementary measures ("toolbox") for their studies. We included 101 peer
reviewed articles that evaluate consumer's emotions and were published between
1997 and 2016, providing us with 59 different measures. More than 60% of these
measures are based on self-reported, subjective ratings and questionnaires
(cognitive measurement level) and assess the conscious/decision-making level of
emotional processing. This multitude of measures and their overrepresentation in
a single category hinders the comparison of results across studies and building a
complete multi-faceted picture of food-evoked emotions. We recommend (1) to use
widely applied, validated measures only, (2) to refrain from using (highly
correlated) measures from the same category but use measures from different
categories instead, preferably covering all three emotional processing levels,
and (3) to acquire and share simultaneously collected physiological, behavioral,
and cognitive datasets to improve the predictive power of food choice and other
models.
PMID- 29937745
TI - Does Sleep Help Prevent Forgetting Rewarded Memory Representations in Children
and Adults?
AB - Sleep fosters the consolidation of rewarded memory representations in adults.
However, sleep and its memory-supporting functions change through healthy
development, and it is unclear whether sleep benefits the consolidation of
rewarded memory representations in children as it does in adults. Based on
previous findings, we expected sleep to benefit the consolidation of rewarded
memory representations in children more than it does in adults. For that reason,
16 children (7-11 years) and 20 adults (21-29 years) participated in this
experiment. During the encoding session, participants were asked to learn the
location of 18 object pairs. Thereafter, one-half of the object locations were
allocated to a high-rewarded condition and the other half to a low-rewarded
condition. In the sleep condition, the encoding session took place in the evening
(for children 7-8 pm, for adults 8-9 pm). After a fixed retention interval of 12
h the retrieval session was conducted the next morning (for children 7-8 am, for
adults 8-9 am). In the wake condition, the time schedule was the same but
reversed: the encoding session started in the morning (for children 7-8 am, for
adults 8-9 am), and retrieval took place in the evening (for children 7-8 pm, for
adults 8-9 pm). Sleep/wake had no impact on the memory performance regarding the
low-rewarded memory items. In contrast, wakefulness in comparison to sleep
reduced the memory performance on high-rewarded memory items. The interaction
between sleep/wake and the degree of reward on memory performance was only
significant in children. These results show that 12 h of wakefulness can
deteriorate the memory performance for high-rewarded representations, whereas
sleep can prevent the forgetting of these rewarded representations. It is
discussed whether ontogenetic changes in sleep may play a role in conserving
relevant but fragile memory representation.
PMID- 29937747
TI - Fostering Children's Connection to Nature Through Authentic Situations: The Case
of Saving Salamanders at School.
AB - The aim of this paper is to explore how children learn to form new relationships
with nature. It draws on a longitudinal case study of children participating in a
stewardship project involving the conservation of salamanders during the school
day in Stockholm, Sweden. The qualitative method includes two waves of data
collection: when a group of 10-year-old children participated in the project
(2015) and 2 years after they participated (2017). We conducted 49 interviews
with children as well as using participant observations and questionnaires. We
found indications that children developed sympathy for salamanders and increased
concern and care for nature, and that such relationships persisted 2 years after
participation. Our rich qualitative data suggest that whole situations of
sufficient unpredictability triggering free exploration of the area, direct
sensory contact and significant experiences of interacting with a species were
important for children's development of affective relationships with the
salamander species and with nature in an open-ended sense. Saving the lives of
trapped animals enabled direct sensory interaction, feedback, increased
understanding, and development of new skills for dynamically exploring further
ways of saving species in an interactive process experienced as deeply
meaningful, enjoyable and connecting. The behavioral setting instilled a sense of
pride and commitment, and the high degree of responsibility given to the children
while exploring the habitat during authentic situations enriched children's
enjoyment. The study has implications for the design of education programs that
aim to connect children with nature and for a child-sensitive urban policy that
supports authentic nature situations in close spatial proximity to preschools and
schools.
PMID- 29937746
TI - The Influence of Fluid Intelligence, Executive Functions and Premorbid
Intelligence on Memory in Frontal Patients.
AB - Objective: It is commonly thought that memory deficits in frontal patients are a
result of impairments in executive functions which impact upon storage and
retrieval processes. Yet, few studies have specifically examined the relationship
between memory performance and executive functions in frontal patients.
Furthermore, the contribution of more general cognitive processes such as fluid
intelligence and demographic factors such as age, education, and premorbid
intelligence has not been considered. Method: Our study examined the relationship
between recall and recognition memory and performance on measures of fluid
intelligence, executive functions and premorbid intelligence in 39 frontal
patients and 46 healthy controls. Results: Recall memory impairments in frontal
patients were strongly correlated with fluid intelligence, executive functions
and premorbid intelligence. These factors were all found to be independent
predictors of recall performance, with fluid intelligence being the strongest
predictor. In contrast, recognition memory impairments were not related to any of
these factors. Furthermore, age and education were not significantly correlated
with either recall or recognition memory measures. Conclusion: Our findings show
that recall memory in frontal patients was related to fluid intelligence,
executive functions and premorbid intelligence. In contrast, recognition memory
was not. These findings suggest that recall and recognition memory deficits
following frontal injury arise from separable cognitive factors. Recognition
memory tests may be more useful when assessing memory functions in frontal
patients.
PMID- 29937748
TI - Older Workers and Affective Job Satisfaction: Gender Invariance in Spain.
AB - Older employees' affective job satisfaction is an aspect that arouses growing
interest among researchers. Among the affective measures of job satisfaction, the
Brief Index of Affective Job Satisfaction (BIAJS) is one of the most used in the
last decade. This study is intended to the test the gender invariance of the
BIAJS in two samples of workers over age 40 in Spain. The first sample, of 300
participants and the second sample, of 399 participants, have been used to test
gender invariance of the BIAJS. In comparison with the original English version,
the Spanish version of the BIAJS has adequate psychometric properties. The
findings allow us to consider it a valid and reliable tool to assess older
people's affective expressions about their work. In addition, this study provides
evidence of its factorial invariance as a function of gender.
PMID- 29937749
TI - Spontaneous Cognition and Epistemic Agency in the Cognitive Niche.
AB - According to Thomas Metzinger, many human cognitive processes in the waking state
are spontaneous and are deprived of the experience of epistemic agency. He
considers mind wandering as a paradigm example of our recurring loss of epistemic
agency. I will enrich this view by extending the scope of the concept of
epistemic agency to include cases of depressive rumination and creative
cognition, which are additional types of spontaneous cognition. Like mind
wandering, they are characterized by unique phenomenal and functional properties
that give rise to varying degrees of epistemic agency. The main claim of this
paper will be that the experience of being an epistemic agent within a certain
time frame is a relational phenomenon that emerges from the organism's capacity
to interact with its cognitive niche. To explore this relation, I develop a new
framework that integrates phenomenological considerations on epistemic agency
with a functional account of the reciprocal coupling of the embodied organism
with its cognitive niche. This account rests upon dynamical accounts of strong
embodied and embedded cognition and recent work on cognitive niche construction.
Importantly, epistemic agency and organism-niche coupling are gradual phenomena
ranging from weak to strong realizations. The emerging framework will be employed
to analyze mind wandering, depressive rumination, and creative cognition as well
as their commonalities and differences. Mind wandering and depressive rumination
are cases of weak epistemic agency and organism-niche coupling. However, there
are also important phenomenological, functional, and neuronal differences. In
contrast, creative cognition is a case of strong epistemic agency and organism
niche coupling. By providing a phenomenological and functional analysis of these
distinct types of spontaneous cognition, we can gain a better understanding of
the importance of organism-niche interaction for the realization of epistemic
agency.
PMID- 29937750
TI - The Effect of Target Sex, Sexual Dimorphism, and Facial Attractiveness on
Perceptions of Target Attractiveness and Trustworthiness.
AB - Facial sexual dimorphism has widely demonstrated as having an influence on the
facial attractiveness and social interactions. However, earlier studies show
inconsistent results on the effect of sexual dimorphism on facial attractiveness
judgments. Previous studies suggest that the level of attractiveness might work
as a moderating variable among the relationship between sexual dimorphism and
facial preference and have often focused on the effect of sexual dimorphism on
general attractiveness ratings, rather than concentrating on trustworthiness
perception. Male and female participants viewed target male and female faces that
varied on attractiveness (more attractive or less attractive) and sexual
dimorphism (masculine or feminine). Participants rated the attractiveness of the
faces and reported how much money they would give to the target person as a
measure of trust. For the facial attractiveness ratings, (a) both men and women
participants preferred masculine male faces to feminine male ones under the more
attractive condition, whereas preferred feminine male faces to masculine male
ones under the less attractive condition; (b) all participants preferred feminine
female faces to masculine female ones under the less attractive condition, while
there were no differences between feminine female faces and masculine female
faces under the more attractive condition. For the target trustworthiness
perception, (a) participants showed no preference between masculine male faces
and feminine male faces, neither under the more attractive condition nor the less
attractiveness condition; (b) however, all the participants preferred masculine
female faces over feminine female faces under the more attractive condition,
exhibiting no preference between feminine female faces and masculine female faces
under the less attractive condition. These findings suggest that the
attractiveness of facial stimulus may be a reason to interpret the inconsistent
results from the previous studies, which focused on the effect of facial sexual
dimorphism on the facial attractiveness. Furthermore, implications about the
effect of target facial sexual dimorphism on participants' trustworthiness
perception were discussed.
PMID- 29937751
TI - Onset Symptoms, Tobacco Smoking, and Progressive-Onset Phenotype Are Associated
With a Delayed Onset of Multiple Sclerosis, and Marijuana Use With an Earlier
Onset.
AB - Background: Age at symptom onset (ASO) is a prognostic factor that could affect
the accrual of disability in multiple sclerosis (MS) patients. Some factors are
known to influence the risk of multiple sclerosis (MS), but their influence on
the ASO is less well-investigated. Objective: Examine the associations between
known or emerging MS risk factors and ASO. Methods: This was a multicenter study,
incident cases (n = 279) with first clinical diagnosis of demyelinating event
aged 18-59 years recruited at four Australian centres (latitudes 27 degrees -43
degrees S), from 1 November 2003 to 31 December 2006. Environmental/behavioral
variables and initial symptoms were recorded at baseline interview. Linear
regression was used to assess the association between risk factors and ASO.
Results: Five factors were significantly associated with ASO: a history of
tobacco smoking was associated with 3.05-years later ASO (p = 0.002); a history
of marijuana use was associated with 6.03-years earlier ASO (p < 0.001);
progressive-onset cases had 5.61-years later ASO (p = 0.001); an initial
presentation of bowel & bladder and cerebral dysfunctional were associated with
3.39 (p = 0.017) and 4.37-years (p = 0.006) later ASO, respectively. Other
factors, including sex, offspring number, latitude of study site, history of
infectious mononucleosis, HLA-DR15 & HLA-A2 genotype, 25(OH)D levels, and
ultraviolet radiation exposure were not associated with ASO. Including all five
significant variables into one model explained 12% of the total variance in ASO.
Conclusion: We found a novel association between a history of tobacco smoking and
later onset, whereas marijuana use was associated with earlier onset. Behavioral
factors seem important drivers of MS onset timing although much of the variance
remains unexplained.
PMID- 29937752
TI - Multiple Sclerosis in the Asia Pacific Region: A Systematic Review of a Neglected
Neurological Disease.
AB - Background: Multiple sclerosis is thought to be relatively uncommon in the Asia
Pacific region with prevalence estimated between 0 and 20 per 100,000. There is
reason to doubt these estimates due to the lack of data from many countries and
the growing evidence of variability in prevalence across small geographic areas.
This study was conducted to systematically review the population prevalence,
incidence, mortality and disability progression estimates of MS within the Asia
Pacific region. Methods: The systematic review was conducted on articles from
1985 till 31st July 2017 within the PubMed/MEDLINE, EMBASE, SCOPUS, and The
Cochrane Library databases. The review included articles that were population
based studies conducted on patients with MS in the Asia Pacific region that
reported either incidence, prevalence, mortality, or disease progression.
Hospital-based studies and non-research articles were excluded to ensure that
only information representative of the population was included for analysis. Data
appraisal and extraction was done by independent reviewers. This review was
registered with PROSPERO (ID: CRD42017082760). Findings: Of the 2,757 articles
found, 16 studies were included. Information on 6 (18.75%) of 32 Asia Pacific
countries was found, with data representing 8% of the total population.
Prevalence estimates were available for 6 countries while estimates for incidence
(3 countries), mortality (4 countries), and disease progression (2 countries)
were limited. Interpretation: The lack of epidemiological data available in the
Asia Pacific region creates a blind spot in the surveillance of MS which obscures
the true burden of MS, causing patients to struggle to receive the resources and
funding that they need.
PMID- 29937753
TI - Pituitary Action of E2 in Prepubertal Grass Carp: Receptor Specificity and Signal
Transduction for Luteinizing Hormone and Follicle-Stimulating Hormone Regulation.
AB - 17beta-estradiol (E2) is an important sex steroid produced by ovary and brain. In
mammals, E2 plays an important role in hypothalamus-pituitary-gonad axis to
regulate puberty onset, however, little is known about the functional role of E2
in teleost pituitary. Using prepubertal grass carp as model, three nuclear
estrogen receptors (nERs: estrogen receptor alpha, estrogen receptor beta 1, and
estrogen receptor beta 2) and two G protein-coupled estrogen receptors (GPER1:
GPER1a and GPER1b) were isolated from grass carp pituitary. Tissue distribution
analysis indicated that both nERs and GPERs were highly detected in grass carp
pituitary, which suggested that E2 should play an important role in grass carp
pituitary. Using primary cultured grass carp pituitary cells as model, high
throughput RNA-seq was used to examine the E2-induced differentially expressed
genes (DEGs). Transcriptomic analysis showed that E2 could significantly
upregulate the expression of 28 genes in grass carp pituitary cells, which were
characterized into different functions including reproduction, gonad development,
and central nervous system development. Further studies confirmed that E2 could
induce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion
and mRNA expression in prepubertal grass carp pituitary in vivo and in vitro. In
the pituitary, LH and FSH regulation by E2 were mediated by both ERbeta and
GPER1. Apparently, E2-induced LHbeta and FSHbeta mRNA expression were mediated by
adenylyl cyclase/cAMP/protein kinase A, phospholipase C/inositol 1,4,5
triphosphate/protein kinase C, and Ca2+/calmodulin/CaM-dependent protein kinase
II pathways. In addition to LH and FSH, E2 could also induce growth regulation by
estrogen in breast cancer 1 (a novel regulator for pituitary development) mRNA
expression in grass carp pituitary cells. These results, as a whole, suggested
that E2 could play an important role in gonadotropin hormone release and
pituitary development in prepubertal grass carp.
PMID- 29937754
TI - Optofluidic Single-Cell Genome Amplification of Sub-micron Bacteria in the Ocean
Subsurface.
AB - Optofluidic single-cell genome amplification was used to obtain genome sequences
from sub-micron cells collected from the euphotic and mesopelagic zones of the
northwestern Sargasso Sea. Plankton cells were visually selected and manually
sorted with an optical trap, yielding 20 partial genome sequences representing
seven bacterial phyla. Two organisms, E01-9C-26 (Gammaproteobacteria),
represented by four single cell genomes, and Opi.OSU.00C, an uncharacterized
Verrucomicrobia, were the first of their types retrieved by single cell genome
sequencing and were studied in detail. Metagenomic data showed that E01-9C-26 is
found throughout the dark ocean, while Opi.OSU.00C was observed to bloom
transiently in the nutrient-depleted euphotic zone of the late spring and early
summer. The E01-9C-26 genomes had an estimated size of 4.76-5.05 Mbps, and
contained "O" and "W"-type monooxygenase genes related to methane and ammonium
monooxygenases that were previously reported from ocean metagenomes. Metabolic
reconstruction indicated E01-9C-26 are likely versatile methylotrophs capable of
scavenging C1 compounds, methylated compounds, reduced sulfur compounds, and a
wide range of amines, including D-amino acids. The genome sequences identified
E01-9C-26 as a source of "O" and "W"-type monooxygenase genes related to methane
and ammonium monooxygenases that were previously reported from ocean metagenomes,
but are of unknown function. In contrast, Opi.OSU.00C genomes encode genes for
catabolizing carbohydrate compounds normally associated with eukaryotic
phytoplankton. This exploration of optofluidics showed that it was effective for
retrieving diverse single-cell bacterioplankton genomes and has potential
advantages in microbiology applications that require working with small sample
volumes or targeting cells by their morphology.
PMID- 29937755
TI - Enhanced Bacterial Fitness Under Residual Fluoroquinolone Concentrations Is
Associated With Increased Gene Expression in Wastewater-Derived qnr Plasmid
Harboring Strains.
AB - Plasmids harboring qnr genes confer resistance to low fluoroquinolone
concentrations. These genes are of significant clinical, evolutionary and
environmental importance, since they are widely distributed in a diverse array of
natural and clinical environments. We previously extracted and sequenced a large
(~185 Kbp) qnrB-harboring plasmid, and several small (~8 Kbp) qnrS-harboring
plasmids, from Klebsiella pneumoniae isolates from municipal wastewater
biosolids, and hypothesized that these plasmids provide host bacteria a selective
advantage in wastewater treatment plants (WWTPs) that often contain residual
concentrations of fluoroquinolones. The objectives of this study were therefore
to determine the effect of residual fluoroquinolone concentrations on the growth
kinetics of qnr plasmid-harboring bacteria; and on the copy number of qnr
plasmids and expression of qnr genes. Electrotransformants harboring either one
of the two types of plasmids could grow at ciprofloxacin concentrations exceeding
0.5 MUg ml-1, but growth was significantly decreased at concentrations higher
than 0.1 MUg ml-1. In contrast, plasmid-free strains failed to grow even at 0.05
MUg ml-1. No differences were observed in plasmid copy number under the tested
ciprofloxacin concentrations, but qnr expression increased incrementally from 0
to 0.4 MUg ml-1, suggesting that the transcription of this gene is regulated by
antibiotic concentration. This study reveals that wastewater-derived qnr plasmids
confer a selective advantage in the presence of residual fluoroquinolone
concentrations and provides a mechanistic explanation for this phenomenon.
PMID- 29937756
TI - Canola Root-Associated Microbiomes in the Canadian Prairies.
AB - Canola is one of the most economically important crops in Canada, and the root
and rhizosphere microbiomes of a canola plant likely impact its growth and
nutrient uptake. The aim of this study was to determine whether canola has a core
root microbiome (i.e., set of microbes that are consistently selected in the root
environment), and whether this is distinct from the core microbiomes of other
crops that are commonly grown in the Canadian Prairies, pea, and wheat. We also
assessed whether selected agronomic treatments can modify the canola microbiome,
and whether this was associated to enhanced yield. We used a field experiment
with a randomized complete block design, which was repeated at three locations
across the canola-growing zone of Canada. Roots and rhizosphere soil were
harvested at the flowering stage of canola. We separately isolated total
extractable DNA from plant roots and from adjacent rhizosphere soil, and
constructed MiSeq amplicon libraries for each of 60 samples, targeting bacterial,
and archaeal 16S rRNA genes and the fungal ITS region. We determined that the
microbiome of the roots and rhizosphere of canola was consistently different from
those of wheat and pea. These microbiomes comprise several putative plant-growth
promoting rhizobacteria, including Amycolatopsis sp., Serratia proteamaculans,
Pedobacter sp., Arthrobacter sp., Stenotrophomonas sp., Fusarium merismoides, and
Fusicolla sp., which correlated positively with canola yield. Crop species had a
significant influence on bacterial and fungal assemblages, especially within the
roots, while higher nutrient input or seeding density did not significantly alter
the global composition of bacterial, fungal, or archaeal assemblages associated
with canola roots. However, the relative abundance of Olpidium brassicae, a known
pathogen of members of the Brassicaceae, was significantly reduced in the roots
of canola planted at higher seeding density. Our results suggest that seeding
density and plant nutrition management modified the abundance of other bacterial
and fungal taxa forming the core microbiomes of canola that are expected to
impact crop growth. This work helps us to understand the microbial assemblages
associated with canola grown under common agronomic practices and indicates
microorganisms that can potentially benefit or reduce the yield of canola.
PMID- 29937757
TI - Fnr and ArcA Regulate Lipid A Hydroxylation in Salmonella Enteritidis by
Controlling lpxO Expression in Response to Oxygen Availability.
AB - Lipid A is the bioactive component of lipopolysaccharide, and presents a dynamic
structure that undergoes modifications in response to environmental signals. Many
of these structural modifications influence Salmonella virulence. This is the
case of lipid A hydroxylation, a modification catalyzed by the dioxygenase LpxO.
Although it has been established that oxygen is required for lipid A
hydroxylation acting as substrate of LpxO in Salmonella, an additional regulatory
role for oxygen in lpxO expression has not been described. The existence of this
regulation could be relevant considering that Salmonella faces low oxygen tension
during infection. This condition leads to an adaptive response by changing the
expression of numerous genes, and transcription factors Fnr and ArcA are major
regulators of this process. In this work, we describe for the first time that
lipid A hydroxylation and lpxO expression are modulated by oxygen availability in
Salmonella enterica serovar Enteritidis (S. Enteritidis). Biochemical and genetic
analyses indicate that this process is regulated by Fnr and ArcA controlling the
expression of lpxO. In addition, according to our results, this regulation occurs
by direct binding of both transcription factors to specific elements present in
the lpxO promoter region. Altogether, our observations revealed a novel role for
oxygen acting as an environment signal controlling lipid A hydroxylation in S.
Enteritidis.
PMID- 29937758
TI - Redox Structures of Humic Acids Derived From Different Sediments and Their
Effects on Microbial Reduction Reactions.
AB - Herein, we investigated the chemical, electrochemical, and spectroscopic
characteristics of humic acids (HAs) extracted from sediments of different origin
[Ling Qiao river, Xi Xi wetland, Qi Zhen lake (QZ), and Hu Zhou pond in Zhejiang
province, China], paying particular attention to their role in the enhancement of
nitrate and FeOOH reduction. Notably, the highest C/N ratio (16.16), O/C ratio
(1.89), and Fe content (11.57 g kg-1 sample) were observed for HAs extracted from
QZ sediment. Cyclic voltammetry analyses confirmed that all HAs contained redox
active groups and exhibited redox potentials between -0.36 and -0.28 V vs. the
standard hydrogen electrode. All HAs showed similar Fourier transform infrared
spectra with variable absorption intensity, the spectra verified the presence of
aromatic C=C, C-H, and C=O of quinone ketones group in HAs. Electron spin
resonance suggested that quinone moieties within HAs are the redox-active
centers. All HAs promoted the microbial reduction of nitrate and amorphous FeOOH
by Shewanella oneidensis strain MR-1, achieving high nitrate reduction extents of
79-98.4%, compared to the biotic and abiotic control values of 29.6 and 0.006%,
respectively. The corresponding extents of Fe(II) production equaled 43.25-60.5%,
exceeding those of biotic and abiotic controls (28.5 and 0.005%, respectively).
In addition to the highest C/N, O/C ratio, and Fe content, HA extracted from QZ
sediment also exhibited the highest nitrate and FeOOH reduction performances.
Although the proportion of organic redox-active carbon is small, the potential
electron-mediating ability is not ignorable. HAs are redox active for enhancing
microbial reduction of nitrate and amorphous FeOOH regardless of the location or
texture of parent sediments, implying their great potential for acting as redox
mediator in enhancing multiple microbial reduction, thereby affecting various
biogeochemical processes (i.e., iron cycle, nitrogen cycle, etc.) as well as in
situ remediation in anaerobic environment.
PMID- 29937759
TI - A Novel Tomato Fusarium Wilt Tolerance Gene.
AB - The reduced mycorrhizal colonization (rmc) tomato mutant is unable to form
mycorrhiza and is more susceptible to Fusarium wilt compared with its wild-type
isogenic line 76R. The rmc mutant has a chromosomal deletion affecting five
genes, one of which is similar to CYCLOPS. Loss of this gene is responsible for
non-mycorrhizality in rmc but not enhanced Fusarium wilt susceptibility. Here, we
describe assessment of a second gene in the rmc deletion, designated
Solyc08g075770 that is expressed in roots. Sequence analyses show that
Solyc08g075770 encodes a small transmembrane protein with putative
phosphorylation and glycosylation sites. It is predicted to be localized in the
plasma membrane and may function in transmembrane ion transport and/or as a cell
surface receptor. Complementation and knock-out strategies were used to test its
function. Some putative CRISPR/Cas-9 knock-out transgenic events exhibited
Fusarium wilt susceptibility like rmc and some putative complementation lines
were 76R-like, suggesting that the tomato Solyc08g075770 functions in Fusarium
wilt tolerance. This is the first study to demonstrate that Solyc08g075770 is the
contributor to the Tfw locus, conferring tolerance to Fusarium wilt in 76R which
was lost in rmc.
PMID- 29937760
TI - Multiple Ribosomal RNA Operons in Bacteria; Their Concerted Evolution and
Potential Consequences on the Rate of Evolution of Their 16S rRNA.
AB - Bacterial species differ greatly in the number and location of the rRNA operons
which may be present in the bacterial chromosomes and plasmids. Most bacterial
species contain more than one ribosomal RNA operon copy in their genomes, with
some species containing up to 15 such copies. We review the number and location
of the rRNA operons and discuss evolution of 16S rRNA (rrs) genes -which are
considered as ultimate chronometers for phylogenetic classification- in bacteria
with multiple copies of these genes. In these bacterial species, the rrs genes
must evolve in concert and sequence changes generated by mutation or horizontal
gene transfer must be either erased or spread to every gene copy to avoid
divergence, as it occurs when they are present in different species. Analysis of
polymorphic sites in intra-genomic rrs copies identifies putative conversion
events and demonstrates that sequence conversion is patchy and occurs in small
conversion tracts. Sequence conversion probably arises by a non-reciprocal
transfer between two or more copies where one copy contributes only a small
contiguous segment of DNA, whereas the other copy contributes the rest of the
genome in a fairly well understood molecular process. Because concerted evolution
implies that a mutation in any of the rrs copies is either eliminated or
transferred to every rrs gene in the genome, this process should slow their
evolution rate relative to that of single copy genes. However, available data on
the rrs genes in bacterial genomes do not show a clear relationship between their
evolution rates and the number of their copies in the genome.
PMID- 29937762
TI - Microbial Interactions With Dissolved Organic Matter Drive Carbon Dynamics and
Community Succession.
AB - Knowledge of dynamic interactions between natural organic matter (NOM) and
microbial communities is critical not only to delineate the routes of NOM
degradation/transformation and carbon (C) fluxes, but also to understand
microbial community evolution and succession in ecosystems. Yet, these processes
in subsurface environments are usually studied independently, and a comprehensive
view has been elusive thus far. In this study, we fed sediment-derived dissolved
organic matter (DOM) to groundwater microbes and continually analyzed microbial
transformation of DOM over a 50-day incubation. To document fine-scale changes in
DOM chemistry, we applied high-resolution Fourier transform ion cyclotron
resonance mass spectrometry (FT-ICR MS) and soft X-ray absorption spectroscopy
(sXAS). We also monitored the trajectory of microbial biomass, community
structure and activity over this time period. Together, these analyses provided
an unprecedented comprehensive view of interactions between sediment-derived DOM
and indigenous subsurface groundwater microbes. Microbial decomposition of labile
C in DOM was immediately evident from biomass increase and total organic carbon
(TOC) decrease. The change of microbial composition was closely related to DOM
turnover: microbial community in early stages of incubation was influenced by
relatively labile tannin- and protein-like compounds; while in later stages the
community composition evolved to be most correlated with less labile lipid- and
lignin-like compounds. These changes in microbial community structure and
function, coupled with the contribution of microbial products to DOM pool
affected the further transformation of DOM, culminating in stark changes to DOM
composition over time. Our study demonstrates a distinct response of microbial
communities to biotransformation of DOM, which improves our understanding of
coupled interactions between sediment-derived DOM, microbial processes, and
community structure in subsurface groundwater.
PMID- 29937761
TI - Epstein-Barr Virus-Induced Metabolic Rearrangements in Human B-Cell Lymphomas.
AB - Tumor metabolism has been the object of several studies in the past, leading to
the pivotal observation of a consistent shift toward aerobic glycolysis (so
called Warburg effect). More recently, several additional investigations proved
that tumor metabolism is profoundly affected during tumorigenesis, including
glucose, lipid and amino-acid metabolism. It is noticeable that metabolic
reprogramming can represent a suitable therapeutic target in many cancer types.
Epstein-Barr virus (EBV) was the first virus linked with cancer in humans when
Burkitt lymphoma (BL) was described. Besides other well-known effects, it was
recently demonstrated that EBV can induce significant modification in cell
metabolism, which may lead or contribute to neoplastic transformation of human
cells. Similarly, virus-induced tumorigenesis is characterized by relevant
metabolic abnormalities directly induced by the oncoviruses. In this article, the
authors critically review the most recent literature concerning EBV-induced
metabolism alterations in lymphomas.
PMID- 29937763
TI - Comparative Transcriptome Analysis Between a Spontaneous Albino Mutant and Its
Sibling Strain of Cordyceps militaris in Response to Light Stress.
AB - Albinism has been used for new variety screening in some edible mushrooms and the
underlying mechanisms are fascinating. Albino fruiting body of Cordyceps
militaris, a well-known edible fungus and model organism for Cordyceps, has the
potential to be a nutraceutical or functional food due to its high content of
metabolites and antioxidant activities. In this study, a spontaneous albino
mutant strain (505) of C. militaris was obtained. In comparison to its normal
sibling strain (498), the albino strain stably remained white in response to
light and had significantly decreased conidia and carotenoid production but
accumulated more cordycepin. Transcriptome analysis of both strains revealed that
all the seven photoreceptors were expressed similarly in response to light.
However, many more genes in the albino strain were differentially expressed in
response to light than its sibling strain. The significantly enriched pathways in
498L vs. 505L were mainly associated with replication and repair. Some secondary
metabolite backbone genes including those encoding DMAT, two NRPS-like proteins,
three NPRS, and lanosterol synthase were differentially expressed in the albino
when compared with that of the normal strains. Transcriptome and real-time
quantitative PCR analyses indicated that some cytochrome P450s and
methyltransferases might be related to the phenotypic differences observed
between the two strains. This study compared the genome-wide transcriptional
responses to light irradiation in a spontaneous albino mutant and its normal
sibling strain of an edible fungus, and these findings potentially pave the way
for further investigation of the pigment biosynthetic pathway.
PMID- 29937764
TI - In Silico Genome-Wide Analysis Reveals the Potential Links Between Core Genome of
Acidithiobacillus thiooxidans and Its Autotrophic Lifestyle.
AB - The coinage "pan-genome" was first introduced dating back to 2005, and was used
to elaborate the entire gene repertoire of any given species. Core genome
consists of genes shared by all bacterial strains studied and is considered to
encode essential functions associated with species' basic biology and phenotypes,
yet its relatedness with bacterial lifestyle of the species remains elusive. We
performed the pan-genome analysis of sulfur-oxidizing acidophile
Acidithiobacillus thiooxidans as a case study to highlight species' core genome
and its relevance with autotrophic lifestyle of bacterial species. The
mathematical modeling based on bacterial genomes of A. thiooxidans species,
including a novel strain ZBY isolated from Zambian copper mine plus eight other
recognized strains, was attempted to extrapolate the expansion of its pan-genome,
suggesting that A. thiooxidans pan-genome is closed. Further investigation
revealed a common set of genes, many of which were assigned to metabolic
profiles, notably with respect to energy metabolism, amino acid metabolism, and
carbohydrate metabolism. The predicted metabolic profiles of A. thiooxidans were
characterized by the fixation of inorganic carbon, assimilation of nitrogen
compounds, and aerobic oxidation of various sulfur species. Notably, several
hydrogenase (H2ase)-like genes dispersed in core genome might represent the novel
classes due to the potential functional disparities, despite being closely
related homologous genes that code for H2ase. Overall, the findings shed light on
the distinguishing features of A. thiooxidans genomes on a global scale, and
extend the understanding of its conserved core genome pertaining to autotrophic
lifestyle.
PMID- 29937765
TI - Comparative Genomics Provides Insights Into the Marine Adaptation in Sponge
Derived Kocuriaflava S43.
AB - Sponge-derived actinomycetes represent a significant component of marine
actinomycetes. Members of the genus Kocuria are distributed in various habitats
such as soil, rhizosphere, clinical specimens, marine sediments, and sponges,
however, to date, little is known about the mechanism of their environmental
adaptation. Kocuria flava S43 was isolated from a coastal sponge. Phylogenetic
analysis revealed that it was closely related to the terrestrial airborne K.
flava HO-9041. In this study, to gain insights into the marine adaptation in K.
flava S43 we sequenced the draft genome for K. flava S43 by third generation
sequencing (TGS) and compared it with those of K. flava HO-9041 and some other
Kocuria relatives. Comparative genomics and phylogenetic analyses revealed that
K. flava S43 might adapt to the marine environment mainly by increasing the
number of the genes linked to potassium homeostasis, resistance to heavy metals
and phosphate metabolism, and acquiring the genes associated with electron
transport and the genes encoding ATP-binding cassette (ABC) transporter,
aquaporin, and thiol/disulfide interchange protein. Notably, gene acquisition was
probably a primary mechanism of environmental adaptation in K. flava S43.
Furthermore, this study also indicated that the Kocuria isolates from various
marine and hyperosmotic environments possessed common genetic basis for
environmental adaptation.
PMID- 29937766
TI - Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death.
AB - Adenosine triphosphate (ATP) is known to induce cell death in T lymphocytes at
high extracellular concentrations. CD4+ and CD8+ T lymphocytes have a
differential response to ATP, which in mice is due to differences in the P2X7
receptor expression levels. By contrast, we observed that the difference in human
CD4+ and CD8+ T lymphocyte response toward the synthetic ATP-analog BzATP is not
explained by a difference in human P2X7 receptor expression. Rather, the BzATP
induced human P2X7 receptor response in naive and immune-activated lymphocyte
subtypes correlated with the expression of another ATP-binding receptor: the
human P2Y11 receptor. In a recombinant expression system, the coexpression of the
human P2Y11 receptor counteracted BzATP-induced human P2X7 receptor-driven
lactate dehydrogenase release (a marker of cell death) and pore formation
independent of calcium signaling. A mutated non-signaling human P2Y11 receptor
had a similar human P2X7 receptor-inhibitory effect on pore formation, thus
demonstrating that the human P2X7 receptor interference was not caused by human
P2Y11 receptor signaling. In conclusion, we demonstrate an important species
difference in the ATP-mediated cell death between mice and human cells and show
that in human T lymphocytes, the expression of the human P2Y11 receptor
correlates with human P2X7 receptor-driven cell death following BzATP
stimulation.
PMID- 29937767
TI - ABCA1, apoA-I, and BTN3A1: A Legitimate Menage a Trois in Dendritic Cells.
AB - Human Vgamma9Vdelta2 T cells have the capacity to detect supra-physiological
concentrations of phosphoantigens (pAgs) generated by the mevalonate (Mev)
pathway of mammalian cells under specific circumstances. Isopentenyl
pyrophosphate (IPP) is the prototypic pAg recognized by Vgamma9Vdelta2 T cells. B
cell derived tumor cells (i.e., lymphoma and myeloma cells) and dendritic cells
(DCs) are privileged targets of Vgamma9Vdelta2 T cells because they generate
significant amounts of IPP which can be boosted with zoledronic acid (ZA). ZA is
the most potent aminobisphosphonate (NBP) clinically available to inhibit
osteoclast activation and a very potent inhibitor of farnesyl pyrophosphate
synthase in the Mev pathway. ZA-treated DCs generate and release in the
supernatants picomolar IPP concentrations which are sufficient to induce the
activation of Vgamma9Vdelta2 T cells. We have recently shown that the ATP-binding
cassette transporter A1 (ABCA1) plays a major role in the extracellular release
of IPP from ZA-treated DCs. This novel ABCA1 function is fine-tuned by physical
interactions with IPP, apolipoprotein A-I (apoA-I), and butyrophilin-3A1
(BTN3A1). The mechanisms by which soluble IPP induces Vgamma9Vdelta2 T-cell
activation remain to be elucidated. It is possible that soluble IPP binds to
BTN3A1, apoA-I, or other unknown molecules on the cell surface of bystander cells
like monocytes, NK cells, Vgamma9Vdelta2 T cells, or any other cell locally
present. Investigating this scenario may represent a unique opportunity to
further characterize the role of BTN3A1 and other molecules in the recognition of
soluble IPP by Vgamma9Vdelta2 T cells.
PMID- 29937768
TI - Monocyte Subsets Have Distinct Patterns of Tetraspanin Expression and Different
Capacities to Form Multinucleate Giant Cells.
AB - Monocytes are able to undergo homotypic fusion to produce different types of
multinucleated giant cells, such as Langhans giant cells in response to M.
tuberculosis infection or foreign body giant cells in response to implanted
biomaterials. Monocyte fusion is highly coordinated and complex, with various
soluble, intracellular, and cell-surface components mediating different stages of
the process. Tetraspanins, such as CD9, CD63, and CD81, are known to be involved
in cell:cell fusion and have been suggested to play a role in regulating
homotypic monocyte fusion. However, peripheral human monocytes are not
homogenous: they exist as a heterogeneous population consisting of three subsets,
classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical
(CD14+CD16+), at steady state. During infection with mycobacteria, the
circulating populations of intermediate and non-classical monocytes increase,
suggesting they may play a role in the disease outcome. Human monocytes were
separated into subsets and then induced to fuse using concanavalin A. The
intermediate monocytes were able to fuse faster and form significantly larger
giant cells than the other subsets. When antibodies targeting tetraspanins were
added, the intermediate monocytes responded to anti-CD63 by forming smaller giant
cells, suggesting an involvement of tetraspanins in fusion for at least this
subset. However, the expression of fusion-associated tetraspanins on monocyte
subsets did not correlate with the extent of fusion or with the inhibition by
tetraspanin antibody. We also identified a CD9High and a CD9Low monocyte
population within the classical subset. The CD9High classical monocytes expressed
higher levels of tetraspanin CD151 compared to CD9Low classical monocytes but the
CD9High classical subset did not exhibit greater potential to fuse and the role
of these cells in immunity remains unknown. With the exception of dendrocyte
expressed seven transmembrane protein, which was expressed at higher levels on
the intermediate monocyte subset, the expression of fusion-related proteins
between the subsets did not clearly correlate with their ability to fuse. We also
did not observe any clear correlation between giant cell formation and the
expression of pro-inflammatory or fusogenic cytokines. Although tetraspanin
expression appears to be important for the fusion of intermediate monocytes, the
control of multinucleate giant cell formation remains obscure.
PMID- 29937769
TI - Gamma Delta T Cell Therapy for Cancer: It Is Good to be Local.
AB - Human gamma delta T cells have extraordinary properties including the capacity
for tumor cell killing. The major gamma delta T cell subset in human beings is
designated Vgamma9Vdelta2 and is activated by intermediates of isoprenoid
biosynthesis or aminobisphosphonate inhibitors of farnesyldiphosphate synthase.
Activated cells are potent for killing a broad range of tumor cells and
demonstrated the capacity for tumor reduction in murine xenotransplant tumor
models. Translating these findings to the clinic produced promising initial
results but greater potency is needed. Here, we review the literature on gamma
delta T cells in cancer therapy with emphasis on the Vgamma9Vdelta2 T cell
subset. Our goal was to examine obstacles preventing effective Vgamma9Vdelta2 T
cell therapy and strategies for overcoming them. We focus on the potential for
local activation of Vgamma9Vdelta2 T cells within the tumor environment to
increase potency and achieve objective responses during cancer therapy. The gamma
delta T cells and especially the Vgamma9Vdelta2 T cell subset, have the potential
to overcome many problems in cancer therapy especially for tumors with no known
treatment, lacking tumor-specific antigens for targeting by antibodies and CAR-T,
or unresponsive to immune checkpoint inhibitors. Translation of amazing work from
many laboratories studying gamma delta T cells is needed to fulfill the promise
of effective and safe cancer immunotherapy.
PMID- 29937770
TI - The Defense-Related Isoleucic Acid Differentially Accumulates in Arabidopsis
Among Branched-Chain Amino Acid-Related 2-Hydroxy Carboxylic Acids.
AB - The branched-chain amino acid (BCAA) related 2-hydroxy carboxylic acid isoleucic
acid (ILA) enhances salicylic acid-mediated pathogen defense in Arabidopsis
thaliana. ILA has been identified in A. thaliana as its glucose conjugate
correlated with the activity of the small-molecule glucosyltransferase UGT76B1,
which can glucosylate both salicylic acid and ILA in vitro. However, endogenous
levels of the ILA aglycon have not yet been determined in planta. To quantify ILA
as well as the related leucic acid (LA) and valic acid (VA) in plant extracts, a
sensitive method based on the derivatization of small carboxylic acids by
silylation and gas chromatography-mass spectrometric analysis was developed. ILA
was present in all species tested including several monocotyledonous and
dicotyledonous plants as well as broadleaf and coniferous trees, whereas LA and
VA were only detectable in a few species. In A. thaliana both ILA and LA were
found. However, their levels varied during plant growth and in root vs. leaves.
ILA levels were higher in 2-week-old leaves and decreased in older plants,
whereas LA exhibited a reverted accumulation pattern. Roots displayed higher ILA
and LA levels compared to leaves. ILA was inversely related to UGT76B1 expression
level indicating that UGT76B1 glucosylates ILA in planta. In contrast, LA was not
affected by the expression of UGT76B1. To address the relation of both 2-hydroxy
acids to plant defense, we studied ILA and LA levels upon infection by
Pseudomonas syringae. LA abundance remained unaffected, whereas ILA was reduced.
This change suggests an ILA-related attenuation of the salicylic acid response.
Collectively, the BCAA-related ILA and LA differentially accumulated in
Arabidopsis, supporting a specific role and regulation of the defense-modulating
small-molecule ILA among these 2-hydroxy acids. The new sensitive method will
pave the way to further unravel their role in plants.
PMID- 29937772
TI - Editorial: Nutrigenomics in Animal Health and Production.
PMID- 29937771
TI - Molecular Profiling of Pierce's Disease Outlines the Response Circuitry of Vitis
vinifera to Xylella fastidiosa Infection.
AB - Pierce's disease is a major threat to grapevines caused by the bacterium Xylella
fastidiosa. Although devoid of a type 3 secretion system commonly employed by
bacterial pathogens to deliver effectors inside host cells, this pathogen is able
to influence host parenchymal cells from the xylem lumen by secreting a battery
of hydrolytic enzymes. Defining the cellular and biochemical changes induced
during disease can foster the development of novel therapeutic strategies aimed
at reducing the pathogen fitness and increasing plant health. To this end, we
investigated the transcriptional, proteomic, and metabolomic responses of
diseased Vitis vinifera compared to healthy plants. We found that several
antioxidant strategies were induced, including the accumulation of gamma
aminobutyric acid (GABA) and polyamine metabolism, as well as iron and copper
chelation, but these were insufficient to protect the plant from chronic
oxidative stress and disease symptom development. Notable upregulation of
phytoalexins, pathogenesis-related proteins, and various aromatic acid
metabolites was part of the host responses observed. Moreover, upregulation of
various cell wall modification enzymes followed the proliferation of the pathogen
within xylem vessels, consistent with the intensive thickening of vessels'
secondary walls observed by magnetic resonance imaging. By interpreting the
molecular profile changes taking place in symptomatic tissues, we report a set of
molecular markers that can be further explored to aid in disease detection,
breeding for resistance, and developing therapeutics.
PMID- 29937773
TI - Epigenetic Discrimination: Emerging Applications of Epigenetics Pointing to the
Limitations of Policies Against Genetic Discrimination.
AB - Over more than two decades, various policies have been adopted worldwide to
restrict the use of individual genetic information for non-medical reasons by
third parties and prevent 'genetic discrimination'. In this paper, we bring
attention to the growing interest for individual epigenetic information by
insurers and forensic scientists. We question whether such interest could lead to
'epigenetic discrimination' - the differential adverse treatment or abusive
profiling of individuals or groups based on their actual or presumed epigenetic
characteristics - and argue that we might already be facing the limitations of
recently adopted normative approaches against genetic discrimination. First, we
highlight some similarities and differences between genetic and epigenetic
modifications, and stress potential challenges to regulating epigenetic
discrimination. Second, we argue that most existing normative approaches against
genetic discrimination fall short in providing oversight into the field of
epigenetics. We conclude with a call for discussion on the issue, and the
development of comprehensive and forward-looking preventive strategies against
epigenetic discrimination.
PMID- 29937775
TI - Advances in diagnosis and non-surgical treatment of Bell's palsy.
AB - Bell's palsy is a commonly seen cranial nerve disease and can result in
compromised facial appearance and functions. Its etiology, prognosis and
treatment are still being debated. This paper is a review of recent development
in the understanding of etiology, diagnosis and non-surgical treatment of Bell's
palsy.
PMID- 29937774
TI - Advances in microvascular decompression for hemifacial spasm.
AB - Primary hemifacial spasm (HFS) is a disorder that causes frequent involuntary
contractions in the muscles on one side of the face, due to a blood vessel
compressing the nerve at its root exit zone (REZ) from the brainstem. Numerous
prospective and retrospective case series have confirmed the efficacy of
microvascular decompression (MVD) of the facial nerve in patients with HFS.
However, while MVD is effective, there are still significant postoperative
complications. In this paper, recent technological advances related to MVD (such
as lateral spread response, brainstem auditory evokes potential, three
dimensional time of flight magnetic resonance angiography, intraoperative
neuroendoscopy) are reviewed for the purposes of improving MVD treatment efficacy
and reducing postoperative complications.
PMID- 29937776
TI - Optimizing CT for the evaluation of vestibular aqueduct enlargement: Inter-rater
reproducibility and predictive value of reformatted CT measurements.
AB - Enlarged vestibular aqueduct (EVA), the most frequent identifiable cause of
congenital hearing loss, is evaluated with high-definition multi-detector CT in
the axial plane. Our purpose was to determine which reformatted CT measurements
are most reproducible. Seven multiplanar reformatted images were created for each
of the 64 temporal bones in patients with EVA. Intraclass correlation
coefficients (ICC) were used to assess inter-observer variability, and both
linear regression and ROC analyses were used to compare the measurements with
severity of hearing loss, as assessed by pure tone audiometry. All seven
measurements had excellent inter-observer variability, with average-measure ICC
ranging from 0.92 to 0.98. There was no statistically significant correlation
between the radiologic degree of aqueduct enlargement and severity of hearing
loss using any of the seven measurements; ROC analyses revealed areas under the
curves ranging from 0.57 to 0.73. Optimal accuracy was obtained with a threshold
of 1.75 mm as measured at the aqueductal aperture in the Poschl plane, with
sensitivity of 0.75 and specificity of 0.63. Although the radiologic measurement
may not serve as a reliable tool for assessing severity of EVA, Poschl plane
reformatting has proven to be better than conventional axial acquisition plane
for identifying patients with clinically significant hearing loss.
PMID- 29937777
TI - The distance between stapedial footplate and incus in otosclerosis surgery.
AB - Background: The measurement of the piston length during stapedotomy is important
and it may have significant effects on the surgical outcome. Objective: To
determine the piston length in a group of otosclerosis patients who underwent
primary stapedotomy. Material and methods: Between Sep 2013 and Sep 2014, 85
patients with diagnosed otosclerosis underwent primary stapedotomy. Teflon
prosthesis of 0.6 mm of diameter was used in all patients. The distance between
medial surface of the long process of incus and center point of the stapedial
footplate measured. The piston length calculated by adding 0.25 mm for the
thickness of footplate and 0.50 mm for placement of the prosthesis into the
vestibule. Results: The distance between stapedial foot plate and incus ranged
from 3.50 to 4.50 mm. The mean distance was 3.95 +/- 0.16 mm. In majority of
cases (74.1%) piston length was 4.75 mm followed by 4.50 mm in 15.3% and 5.00 mm
in 5.9%. Piston length was 4.25 mm in 3.5% and 5.25 mm in only 1.2% of patients.
There was no significant post-operative complication and air bone gap closure
obtained in all patients. Conclusion: The most common distance between foot plate
and incus is 4.00 mm. No case needed a piston longer than 5.25 mm or shorter than
4.25 mm.
PMID- 29937778
TI - Spatial learning and memory deficits in young adult mice exposed to a brief
intense noise at postnatal age.
AB - Noise pollution is a major hazardous factor to human health and is likely harmful
for vulnerable groups such as pre-term infants under life-support system in an
intensive care unit. Previous studies have suggested that noise exposure impairs
children's learning ability and cognitive performance and cognitive functions in
animal models in which the effect is mainly attributed to the oxidant stress of
noise on the cognitive brain. The potential role of noise induced hearing loss
(NIHL), rather than the oxidant stress, has also been indicated by a depression
of neurogenesis in the hippocampus long after a brief noise exposure, which
produces only a tentative oxidant stress. It is not clear if noise exposure and
NIHL during early development exerts a long term impact on cognitive function and
neurogenesis towards adulthood. In the present study, a brief noise exposure at
high sound level was performed in neonatal C57BL/6J mice (15 days after birth) to
produce a significant amount of permanent hearing loss as proved 2 months after
the noise. At this age, the noise-exposed animals showed deteriorated spatial
learning and memory abilities and a reduction of hippocampal neurogenesis as
compared with the control. The averaged hearing threshold was found to be
strongly correlated with the scores for spatial learning and memory. We consider
the effects observed are largely due to the loss of hearing sensitivity, rather
than the oxidant stress, due to the long interval between noise exposure and the
observations.
PMID- 29937779
TI - Imaging assessment of profound sensorineural deafness with inner ear anatomical
abnormalities.
AB - Objective: To explore the value of a combined computed tomography (CT) and
magnetic resonance imaging (MRI) in evaluating profound sensorineural deafness
patients before cochlear implant (CI) surgery. Methods: A retrospective analysis
of 1012 cases of profound sensorineural deafness that received CI was performed.
Results: A total of 96 cases were diagnosed with inner ear abnormalities
including large vestibular aqueduct syndrome (LVAS, n = 61), Michel deformity (n
= 3), cochlear incomplete partition I (n = 2), cochlear incomplete partition II
(n = 6), cochlear hypoplasia with vestibular malformation (n = 3), cochlear
ossification (n = 3), bilateral internal auditory canal obstruction (n = 5) and
internal auditory canal stenosis (n = 2). Conclusion: High resolution CT (HRCT)
can display bony structures while MRI can image the membranous labyrinth in
preoperative evaluation for cochlear implantation. The combination of these two
modalities provides reliable anatomical information regarding the bony and
membranous labyrinths, as well as the auditory nerve.
PMID- 29937780
TI - Measurement and analysis of associated mimic muscle movements.
AB - OBJECTIVE: To measure movements of markers over the primary site and associated
mimic muscles in certain facial expressions, for evaluating facial paresis and
synkinesis. METHODS: Participants included 22 normal subjects aged 45-66 years.
Maximum shift (Smax) and velocity (Vmax) were measured using a custom-designed 3
D dynamic quantitative analysis system of facial motion (3-D ASFM) based on
motion capture technology. Measures were taken from peri-oral muscles during
forceful brow raising and tight eye closure, and from muscles around the eye
during grinning, right/left/bilateral mouth corner raising and smiling. RESULTS:
1) During forceful brow raising, Smax was 3.65-4.46 mm for markers over perioral
muscles, with the marker over the nasolabial fold showing a Vmax greater than
others (60.60 mm/s on left and 62.70 mm/s on right). 2) In tight eye closure,
Smax of perioral muscle markers was 1.58-1.92 mm, with Vmax being 11.40-14.76
mm/s. 3) In grinning, the largest eye muscle marker Smax was seen at the lower
lid (3.93 mm on left and 4.15 mm on right) and the smallest at the inner canthus
(1.59 mm on left and 1.53 mm on right), with the largest Vmax seen at the upper
lid and smallest also at the inner canthus (11.71 mm/s on left and 11.09 mm/s on
right). 4) In smiling, the largest non-oral Smax and Vmax were seen at the upper
lid (3.05 mm and 36.14 mm/s on left and 2.53 mm and 28.90 mm/s on right) and the
smallest also at the inner canthus (0.69 mm and 7.22 mm/s on left and 0.77 mm and
7.80 mm/s on right). 5) In right mouth corner raising, Smax and Vmax at lateral
and medial canthus and at lower lid were greater on right than left, while those
at upper lid and brow were slightly greater on left than right. 6) In left mouth
corner raising, Smax and Vmax at lateral canthus and upper and lower lids were
greater on left than right. CONCLUSIONS: There are no absolute immobile points on
the face when making facial expressions. In addition to the primary movement
site, there are associated movements at other points on the face with consistent
Smax and Vmax. In assessing facial paresis and synkinesis, physiological
associated facial movements should be taken into consideration.
PMID- 29937781
TI - Extrinsic sound stimulations and development of periphery auditory synapses.
AB - The development of auditory synapses is a key process for the maturation of
hearing function. However, it is still on debate regarding whether the
development of auditory synapses is dominated by acquired sound stimulations. In
this review, we summarize relevant publications in recent decades to address this
issue. Most reported data suggest that extrinsic sound stimulations do affect,
but not govern the development of periphery auditory synapses. Overall, periphery
auditory synapses develop and mature according to its intrinsic mechanism to
build up the synaptic connections between sensory neurons and/or interneurons.
PMID- 29937782
TI - Improved hearing in noise using new signal processing algorithms with the
CochlearTM Nucleus(r) 6 sound processor.
AB - Objective: To demonstrate the performance benefit of the Automatic Scene
Classifier (SCAN) algorithm available in the Nucleus(r) 6 (CP900 series) sound
processor over the default processing algorithms of the previous generation
Nucleus 5 (CP810) and Freedom(r) HybridTM sound processors. Methods: Eighty-two
cochlear implant recipients (40 Nucleus 5 processor users and 42 Freedom Hybrid
processor users) listened to and repeated AzBio sentences in noise with their
current processor and with the Nucleus 6 processor. Results: The SCAN algorithm
when enabled yielded statistically significant non-inferior and superior
performance when compared to the Nucleus 5 and Freedom Hybrid sound processors
programmed with ASC + ADRO(r). Conclusion: The results of these studies
demonstrate the superior performance and clinical utility of the SCAN algorithm
in the Nucleus 6 processor over the Nucleus 5 and Freedom Hybrid processors.
PMID- 29937783
TI - One-year experience with the CochlearTM Paediatric Implanted Recipient
Observational Study (Cochlear P-IROS) in New Delhi, India.
AB - Background: Currently, there is a significant lack of data concerning long-term
outcomes following paediatric cochlear implantation in terms of quality of life.
There is a need for a long-term, prospective study in this regard. This study
aims at highlighting the preliminary results, one year post surgery of a five
year prospective study. Methods: The CochlearTM Paediatric Implanted Recipient
Observational Study (P-IROS) is a prospective, patient outcomes registry for
routinely implanted children. The study collects data using questionnaires post
surgery and at regular intervals up to five years. Results: At our Centre, 159
cochlear implant surgery procedures were carried out between January 2014 and
December 2014. Category of Auditory Performance II score increased from '0' to
'3' at six months and to '5' at 12 months for children aged 0-3 years, although
this was not statistically significant. However, the same trend was statistically
significant for the age 3-6 year and age 6-10 year brackets. The quality of life
of the child improved significantly. Analysis of communication mode revealed a
statistically significant overall shift to the auditory-oral mode from total
communication. Conclusion: Cochlear implantation is a life-changing intervention.
The evidence in support of what it can achieve safely is clear. However, the
costs associated with it raise the question if it will remain an effective option
for life in all children. The Cochlear P-IROS is an attempt to answer the same
over a five year period. Our study in New Delhi, so far concludes that cochlear
implantation in a population with limited access to funds is very effective, one
year after surgery.
PMID- 29937784
TI - Standardization of experimental animals temporal bone sections.
AB - Preparation of the temporal bone for light microscopy is an important step in
histological studies of the inner ear. Due to the complexity of structures of the
inner ear, it is difficult to measure or compare structures of interest without a
commonly accepted standardized measure of temporal bone sections. Therefore,
standardization of temporal bone sections is very important for histological
assessment of sensory hair cells and peripheral ganglion neurons in the cochlear
and vestibular systems. The standardized temporal bone sectioning is oriented to
a plane parallel to the outer and internal auditory canals. Sections are
collected from the epitympanum to the hypotympanum to reveal layers in the order
of the crista ampullaris of the superior and lateral semicircular canals, macula
utriculi and macula sacculi, superior vestibular ganglion neurons, macula of
saccule and inferior vestibular ganglion neurons, cochlear modiolus,
endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of
the posterior semicircular canal. Moreover, technical details of preparing for
temporal bone sectioning including fixation, decalcification, whole temporal bone
staining, embedding penetration, and embedding orientation are also discussed.
PMID- 29937785
TI - Standardized surgical approaches to ear surgery in rats.
AB - Objective: To describe several approaches of ear surgeries for experimental
studies in rats. Methods: Anesthetized rats were prepared for demonstration of
various ear surgery approaches designed to optimize experimental outcomes in
studies with specific goals and exposure requirements. The surgical approaches
included the posterior tympanum, superior tympanum, inferior tympanum and
occipital approaches. Results: The middle ear cavity and inner ear were
successfully exposed from different angles via the mentioned surgical approaches.
For example, electrode placement for recording of cochlear bioelectric responses
was easily achieved through the posterior tympanum or inferior tympanum approach.
Alternatively, drug delivery or gene transfection via round window membrane was
most easily accomplished using the posterior tympanum approach. Cochlear
perfusion of protective or ototoxic drugs was best performed using the inferior
tympanum approach. Ossicular chain interruption to induce a prolonged conductive
hearing loss was readily achieved using a superior tympanum approach. Lastly,
surgical destruction of the endolymphatic sac to induce experimental
endolymphatic hydrops was readily performed via an occipital surgical approach.
Conclusion: These standardized surgical approaches can be applied in scientific
studies of the ear with different purposes covering electrophysiology, conductive
hearing loss, intra-cochlear drug perfusion and experimental studies relevant to
Meniere's disease.
PMID- 29937786
TI - A novel mutation in POU3F4 in a Chinese family with X-linked non-syndromic
hearing loss.
AB - Objective: Based on the clinical manifestations of a hearing loss patient, the
POU3F4 gene was tested for diagnosis of etiology. Methods: A comprehensive
physical examination was performed on the proband to exclude abnormalities of
other organs, and detailed audiological testing and temporal bone CT scan were
also performed. Genomic DNA was extracted using the proband's peripheral blood
leukocytes. Polymerase chain reactions (PCR) were performed in the coding
sequence of the POU3F4 gene. Direct DNA sequencing was subsequently applied to
screen the entire coding region of the POU3F4 gene. Results: The proband had
severe sensorineural hearing loss. Temporal CT showed bilateral cochlear
incomplete partition, vestibule dysplasia, internal auditory canal fundus
expansion, and cochlear interlink with the internal auditory canal fundus. A
novel mutation (c.530C > A (p.S177X)) in the POU3F4 gene was found in this
patient, creating an new stop codon and was predicted to result in a truncated
protein lacking normal POU3F4 transcription factor function. Conclusion: Through
analysis of the POU3F4 gene and clinical manifestations in the patient, we
conclude that a novel mutation may have resulted in a premature stop codon,
contributing to the mutation of POU3F4 gene.
PMID- 29937787
TI - Transcript variants and expression profiles analysis of Mitf gene in minipigs.
AB - Object: To identify transcript variants and expression patterns of porcine Mitf.
Materials and methods: A pairwise BLAST search at NCBI database was performed to
deduce the structure of porcine Mitf gene. Subsequently, 5' RACE and fluorescent
quantitative RT-PCR were used to analyze the expression pattern of porcine Mitf
in different tissues. Results: Four transcript variants of porcine Mitf, MITF-A,
MITF-H, MITF-M and MITF-SUS were identified, all sharing high homology with those
in humans, except Mitf-SUS. Conclusion: The sequence of porcine Mitf appear
highly homologous to human MITF. However, only 4 transcript variants of porcine
Mitf were identified in these minipigs, less than the 9 transcript variants in
human MITF.
PMID- 29937788
TI - Recording potentials from scala media, saccule and utricle in mice.
AB - Objective: To describe a protocol for recording electrical potentials from the
scala media, saccule, and utricle in mice. Method: CBA/J mice were used and
potentials were recorded with glass electrodes inserted through the basilar
membrane using a patch clamp system. Results: Resting potentials were
successfully recorded from the scala media, saccule and utricle using described
protocols. Conclusions: With the method described, one can measure resting
potentials from the scala media, saccule and utricle, as well as cochlear
microphonics (CM) and even auditory nerve compound action potentials (CAP), in a
single mouse.
PMID- 29937789
TI - Acceptable noise level as a deciding factor for prescribing hearing aids for
older adults with cochlear hearing loss - A scoping review.
AB - Older adults often find it difficult to perceive speech, especially in noisy
conditions. Though hearing aid is one of the rehabilitative devices available to
older adults to alleviate hearing loss, some of them may experience annoyance
through hearing aid and hence reject it, may be due to circuitry noise and/or
background noise. Acceptable noise level is a direct behavioural measure to
estimate the extent of how much a person is able to put up with noise while
simultaneously listening to speech. Acceptable noise level is a central auditory
measure and it is not influenced by age, gender, presentation level or speaker.
Using this measure, we can quantify the annoyance level experienced by an
individual. This information is of utmost importance and caution should be paid
before setting the parameters in hearing aid, especially for those who are unable
to accept noise. In this review article, an attempt has been made to document how
to optimize the hearing aid program by setting parameters such as noise reduction
circuit, microphone sensitivity and gain. These adjustments of parameters might
help to reduce rejection rate of hearing aids, especially in those individuals
who are annoyed by background noise.
PMID- 29937790
TI - Advances in research on labyrinth membranous barriers.
AB - Integrity of the membranous labyrinth barrier system is of critical importance,
which promotes inner ear homeostasis and maintains its features. The membranous
labyrinth barrier system is divided into several subsets of barriers which,
although independent from each other, are interrelated. The same substance may
demonstrate different permeability characteristics through different barriers and
under different conditions, while different substances can have different
permeability features even in the same barrier under the same condition. All
parts of the membranous labyrinth barrier structure, including their morphology,
enzymes and channel proteins, and theirs permeability characteristics under
various physiological and pathological conditions are reviewed in this paper.
Infections, noise exposure, ototoxicity may all increase permeability of the
barriers and lead to disturbances in inner ear homeostasis.
PMID- 29937791
TI - Advantages of a miniature pig model in research on human hereditary hearing loss.
AB - In medical laboratory animals, the pig is the closest species to human in
evolution, except for primates. As an animal model, the pig is highly concerned
by many scientists, including comparative biology, developmental biology, medical
genetics. Rodents as animal model for human hearing defects has are poor
producibility and reliability, due to differences in anatomical structure,
evolutionary rate and metabolic rate, but these happens to be the advantages of
the pig model. In this paper, we will summarize the application of miniature pig
in the study of human hereditary deafness.
PMID- 29937792
TI - The history of CochlearTM Nucleus(r) sound processor upgrades: 30 years and
counting.
AB - To review developments in sound processors over the past 30 years that have
resulted in significant improvements in outcomes for Nucleus(r) recipients.
PMID- 29937793
TI - Quick repositioning maneuver for horizontal semicircular canal benign paroxysmal
positional vertigo.
AB - Objective: To investigate the efficacy of quick repositioning maneuver for
horizontal semicircular canal benign paroxysmal positional vertigo (H-BPPV).
Methods: Clinical data of 67 patients with H-BPPV who underwent quick
repositioning maneuver in our hospital from July 2009 to November 2014 were
retrospectively analyzed. The maneuver involved rotating the patient in the axial
plane for 180 degrees from the involved side towards contralateral side as
quickly as possible. Results: Complete symptom resolution was achieved in 61
patients (91.0%) at one week and in 64 patients (95.5%) at 3 months post
treatment. During the repositioning maneuver process, there were no obvious
untoward responses except transient nausea with or without vomiting in a few
patients. Conclusion: The results indicate that the quick repositioning maneuver
is an easy and effective alternative treatment in the management of H-BPPV.
PMID- 29937794
TI - Characteristic anatomical structures of rat temporal bone.
AB - As most gene sequences and functional structures of internal organs in rats have
been well studied, rat models are widely used in experimental medical studies. A
large number of descriptions and atlas of the rat temporal bone have been
published, but some detailed anatomy of its surface and inside structures remains
to be studied. By focusing on some unique characteristics of the rat temporal
bone, the current paper aims to provide more accurate and detailed information on
rat temporal bone anatomy in an attempt to complete missing or unclear areas in
the existed knowledge. We also hope this paper can lay a solid foundation for
experimental rat temporal bone surgeries, and promote information exchange among
colleagues, as well as providing useful guidance for novice researchers in the
field of hearing research involving rats.
PMID- 29937795
TI - One-stage coclear implantation via a facial recess approach in children with
otitis media with effusion.
AB - Objective: To investigate surgical indications, operative techniques,
complications and auditory and speech rehabilitation for cochlear implant (CI) in
children with otitis media with effusion (OME). Material and methods: This is a
retrospective review of records of 24children with bilateral profound
sensorineural hearing loss and OME who were implanted during January 2011 to
November 2014 in the Department of Otorhinolaryngology and Head and Neck Surgery
at the PLA Hospital, using one-stage implantation via the facial recess approach
and round window insertion. The incus was removed in 8 cases during the
implantation procedure. Local infiltration of dexamethasone and adrenaline in the
middle ear was also performed. Postoperative complications were examined.
Preoperative and postoperative questionnaires including Categories of Auditory
Performance (CAP), Speech Intelligibility Rating (SIR), and the Meaningful
Auditory Integration Scale (MAIS) were collected. Results: All electrodes were
implanted successfully without any immediate or delayed complications.
Inflammatory changes of middle ear mucosa with effusion were noted in all
implanted ears. The scores of post-implant CAP and SIR increased significantly in
all 24 cases (t = -25.95 and -14.09, respectively for CAP and SIR, p < 0.05).
Conclusions: One-stage CI via the facial recess approach with round window
insertion is safe and effective in cochlear implant candidates with OME, as seen
in the 24 children in our study who achieved improved auditory performance and
speech intelligibility after CI.
PMID- 29937796
TI - Cell junction proteins within the cochlea: A review of recent research.
AB - Cell-cell junctions in the cochlea are highly complex and well organized. The
role of these junctions is to maintain structural and functional integrity of the
cochlea. In this review, we describe classification of cell junction-associated
proteins identified within the cochlea and provide a brief overview of the
function of these proteins in adherent junctions, gap junctions and tight
junctions.
PMID- 29937797
TI - Postaurical injection is a systemic delivery supported by symmetric distribution
of Gd-DOTA in both the ipsilateral and contralateral ears.
AB - Postaurical injection of therapeutics was recently applied in clinical practice
to treat inner ear diseases based on supposed existence of a direct channel from
the postaurical area to the inner ear. Doubting on the associated reports and
aiming to provide evidence on the inner ear uptake mechanism, the present study
tracked the dynamic distribution of gadolinium-tetra-azacyclo-dodecane-tetra
acetic acid (Gd-DOTA) in rat inner ears after postaurical injection using MRI. A
targeted tympanic medial wall delivery was utilized as control. The results
showed that, at the early time points after postaurical injection, Gd-DOTA
distributed mainly in tissues surrounding the bulla, temporal bone and skull and
neck space. In the inner ear, there was gradual uptake of Gd-DOTA on both the
ipsilateral and contralateral sides with equal signal intensities. There was no
sign of direct channel carrying the agent from the postaurical area to the inner
ear. Targeted tympanic medial wall delivery induced significantly greater uptake
of Gd-DOTA in the inner ear than did postaurical injection. At 30 min post
administration, targeted tympanic medial wall delivery yielded 4.6-folds higher
signal intensity than did postaurical injection. The total dose of Gd-DOTA
delivered by the targeted tympanic medial wall approach was only 0.1% of that
delivered by postaurical injection. In conclusion, postaurical injection is a
systemic administration, which is similar to hypodermic injection, rather than a
focal delivery method. By contraries, targeted tympanic medial wall delivery
induces fast and abundant uptake of Gd-DOTA in the ipsilateral inner ear without
significant distribution in unwanted areas.
PMID- 29937798
TI - Inflammasome activation in mouse inner ear in response to MCMV induced hearing
loss.
AB - Objective: To identify presence of inflammasome activated in mouse cochlea with
sensorineural hearing loss (SNHL) caused by cytomegalovirus (CMV) infection.
Method: MCMV was injected into the right cerebral hemisphere in neonatal BALB/c
mice at 2000 pfu virus titers. Auditory brainstem responses (ABRs) were tested to
evaluate hearing at 21 days. Histopathological studies were conducted to confirm
localizations of MCMV infected cells in the inner ear. Expression of inflammasome
related factors was assessed by immunofluorescence, Quantitative real-time PCR
and Western blotting. Results: In the mouse model of CMV induced SNHL,
inflammasome related kinase Caspase-1 and downstream inflammatory factor IL-1beta
and IL-18 were found increased and activated after CMV infection in the cochlea.
These factors could further up-regulate expression of IL-6 and TNF-alpha. These
inflammatory factors are neurotoxicity and may contribute to hearing impairment.
Furthermore, we also detected significantly increased AIM2 protein that
accumulated in the SGN of cochleae with CMV infection. Significance: We have
shown that inflammasome as a novel inherent immunity mechanism may contribute to
hearing impairment. Conclusion: Our data indicate that imflammasome assemble in
mouse inner ear in response to CMV infection. We have revealed a novel pathology
event in CMV induced SNHL involving activation of inflammasome in mouse cochlea.
Additionally, we have shown that inflammasome may be a novel target for
prevention and treatment of CMV related SNHL.
PMID- 29937799
TI - Binaural integration abilities in bilateral cochlear implant user.
AB - Bilateral Cochlear implants (CIs) improved speech intelligibility, speech
perception in background noise, and sound localization in quiet and noisy
situations. However, it is unclear whether these advantages essentially result in
binaural integration of acoustic stimuli from each ear. In this study, we
investigated the effectiveness of binaural integration by bilateral CIs placement
using binaural hearing tests and subjective auditory perceptual assessment. A 61
year-old bilateral CIs subject underwent the following four tests: the Japanese
Hearing in Noise Test (HINT-J), the dichotic listening test (DLT), the Rapidly
Alternating Speech Perception (RASP) test, and subjective auditory perceptual
assessment. The HINT-J score was significantly higher for bilateral CIs than for
a unilateral CI. However, DLT and the RASP test revealed contradictory results.
Subjective auditory perceptual assessment revealed active and bright impressions
for bilateral hearing, which were also noisy and strong compared with those for
unilateral hearing. The results of this study revealed that bilateral CIs
improved speech perception in background noise and an improved auditory
impression, although the bilateral integration abilities were not improved. This
was probably because the patient was required to combine information from the two
ears into a single perception in DLT and the RASP test. More longitudinal data
should be collected and analyzed in future studies to evaluate the long-term
effects of bilateral CIs.
PMID- 29937800
TI - Scala tympani drill-out technique for oval window atresia with malformed facial
nerve: A report of three cases.
AB - Objective: To report a scala tympani drill-out technique for managing malformed
facial nerve covering the entire oval window (OW). Methods: Data from three cases
with OW atresia, malformed stapes and abnormal facial nerve courses were
reported, in which a scala tympani drill-out technique was employed with a TORP
between the tympanic membrane and scala tympani fenestration for hearing
reconstruction. Results: Air conduction hearing improved in two of the three
cases following surgery. In the third case, there was no improvement in air
conduction hearing following a canal wall up mastoidectomy and tympanoplasty.
There were no vertigo, tinnitus or sensorineural hearing loss in the three cases.
Conclusion: The scala tympani drill-out technique, which is basically
fenestration at the initial part of the basal turn, provides a choice in hearing
reconstruction when the OW is completely covered by abarrently coursed facial
nerve.
PMID- 29937801
TI - Skin reactions caused by bone-anchored hearing aid (BAHA) implantation.
AB - Objective: To report a case of intractable skin reactions caused by bone-anchored
hearing aid (BAHA) implantation to improve our understanding and treatment of
BAHA implantation-caused skin reactions. Methods: We reported a case of severe
skin reactions caused by BAHA implantation. Related literature were also
reviewed. Results: We found grade IV skin reactions, including hyperplasia around
the implant, which led to the removal of the BAHA implant 10 months after
implantation. The findings indicated poor skin hygiene, allergy to titanium and
inadequate surgicals skills as the possible causes of the skin reaction.
Conclusion: Skin adverse reactions, usually rare in BAHA implantation patients,
may cause implant removal and implantation failure. We suggest to further
investigate the mechanisms underlying titanium allergy.
PMID- 29937802
TI - En bloc resection for treatment of refractory pre-auricular fistula.
AB - Objective: To report a surgical method for the treatment of pre-auricular fistula
to lower post-operative recurrence rate. Methods: Clinical data of 187 patients
with pre-auricular fistula who underwent en bloc resection at the Affiliated
Hospital of Luzhou Medical College from August 2006 to November 2012 were
retrospectively reviewed. Factors that might affect the prognosis following En
bloc fistula resection bordered by the superficial temporalis fascia, helix
perichondrium and auriculocephalic sulcus were investigated. Results: Of the 187
patients, 181 achieved primary healing and 6 ended up with delayed healing.
During the follow-up period (one to seven years), there were 4 cases of
recurrence (2.1%). Conclusions: Clear demarcation of surgical resection can
facilitate easy and thorough resection of preauricular fistula and lead to low
recurrence rate. Proper timing and careful search for potential fistula branches
are the two crucial factors affecting prognosis.
PMID- 29937803
TI - Safety and outcomes of cochlear implantation in the elderly: A review of recent
literature.
AB - Global demographic changes related to longevity are leading to increasing numbers
of the elderly, for whom hearing loss is a significant cause of morbidity and
disability. Once met with reticence, severely hearing impaired older adults are
increasingly being considered for cochlear implantation (CI). Significant data
indicate that CI in the elderly population is safe, well-tolerated, and
effective. Risks from CI surgery and anesthesia are low and generally comparable
to rates in other age groups. Outcomes studies regarding CI in older adults have
shown excellent improvements to speech perception, quality of life, and even
cognition. Overall, currently available data suggests that advanced age should
not, in itself, be considered a barrier to implantation. This review paper will
highlight selected articles from recent medical literature regarding the safety
and efficacy of CI in the elderly population.
PMID- 29937804
TI - Anti-apoptotic treatment in mouse models of age-related hearing loss.
AB - Age-related hearing loss (AHL), or presbycusis, is the most common
neurodegenerative disorder and top communication deficit of the aged population.
Genetic predisposition is one of the major factors in the development of AHL.
Generally, AHL is associated with an age-dependent loss of sensory hair cells,
spiral ganglion neurons and stria vascularis cells in the inner ear. Although the
mechanisms leading to genetic hearing loss are not completely understood, caspase
family proteases function as important signals in the inner ear pathology. It is
now accepted that mouse models are the best tools to study the mechanism of
genetic hearing loss or AHL. Here, we provide a brief review of recent studies on
hearing improvement in mouse models of AHL by anti-apoptotic treatment.
PMID- 29937805
TI - Arsenic ototoxicity.
AB - High levels of arsenic are found in many parts of the world and more than 100
million people may have been exposed to it. There is growing evidence to indicate
that arsenic has a deleterious effect on the auditory system. This paper provides
the general information of arsenic and its ototoxic effects.
PMID- 29937806
TI - A comparison of effects of systemic and intratympanic steroid therapies for
sudden sensorineural hearing loss: A meta-analysis.
AB - Objective: To evaluate the efficacy and safety of intratympanic and systemic
steroid therapies in the initial treatment of Sudden Sensorineural Hearing Loss
(SSNHL) patients. Methods: A comprehensive search of PubMed, Wanfang database and
CNKI (China National Knowledge Infrastructure) was performed covering the period
from January 1990 to July 2014. A meta-analysis was conducted after filtering by
the criteria of Cochrane Collaboration. Three hundred fifty six subjects in nine
studies allocated to the group of intratympanic steroid therapies and 343
controls receiving systemic steroid therapies met the criteria for meta-analysis.
The data were extracted and analyzed using the RevMan 5.3 meta-analysis software.
Results: The total effectiveness rate in SSNHL patients receiving intratympanic
steroid therapies did not differ statistically from patients receiving systemic
therapies (RR = 1.08, 95%CI = 0.99-1.99, P = 0.10), although the rate of full
hearing recovery in this group differed significantly from patients receiving
systemic therapies (RR = 1.29, 95%CI = 1.00-1.66, P = 0.05). Conclusion: Local
steroid therapy appears to generate higher rate of complete hearing recovery than
systemic steroid treatment as an initial treatment for SSNHL, which may be
especially useful for patients in whom systemic steroids are contraindicated.
PMID- 29937807
TI - New language outcome measures for Mandarin speaking children with hearing loss.
AB - Objective: The paper discusses recent evidence on the assessment of language
outcomes in children with hearing loss acquiring oral language. Methods: Research
emphasizes that language tests must be specific enough to capture subtle deficits
in vocabulary and grammar learning at different developmental ages. The
Diagnostic Receptive and Expressive Assessment of Mandarin (DREAM) was carefully
designed to be a comprehensive standardized Mandarin assessment normed in
Mainland China. Results: This paper summarizes the evidence-based item design
process and validity and reliability results of DREAM. A pilot study reported
here shows that DREAM provided detailed information about hearing impaired
children's language abilities and can be used to aid intervention planning to
maximize progress. Conclusion: DREAM represents an example of translational
science, transferring methods from empirical studies of language acquisition in
research environments into applied domains such as assessment and intervention.
Research on outcomes in China will advance significantly with the availability of
evidence-based comprehensive language tests that measure a sufficient age range
of skills, are normed on Mandarin speaking children in mainland China, and are
designed to capture features central to Mandarin language acquisition.
PMID- 29937808
TI - Climatic variations and benign paroxysmal positional vertigo.
AB - Benign paroxysmal positional vertigo (BPPV) is probably the most common diagnosis
at vertigo clinics. Seasonal cycles of several human illnesses could be
attributed variously to changes in atmospheric or weather conditions. In this
retrospective study, patients with BPPV from January 2010 to December 2012 were
studied, and their charts were reviewed. Statistical analysis revealed a
statistically significant difference in patients' numbers among different months
of the year. Also there is a significant statistical correlation between the
numbers of patients with climatic variations especially the temperature. The
present paper discusses the possible explanations for these results which
confirms the seasonal variations in BPPV, together with a review of literature to
view the possible associations with other disorders that causes such seasonality.
PMID- 29937809
TI - Communication outcomes following cochlear implantation in a child with cystic
cochleovestibular anomaly.
AB - Cochlear implantation is one of the best amongst the various management options
available for children and adults with severe to profound sensorineural hearing
loss. Inner ear and internal auditory canal (IAC) malformations accounts to
approximately 25% of congenital sensorineural hearing loss in children. The
primary goal of this report was to evaluate the communication outcomes after
cochlear implantation in a child with cystic cochleovestibular anomaly (CCVA).
The child was evaluated through various standardized outcome measures at regular
intervals to track the progress in terms of auditory and spoken language skills.
The scores on Categories of Auditory Perception (CAP), Meaningful Auditory
Integration Scale (MAIS), Speech Intelligibility Rating (SIR), Meaningful Use of
Speech Scale (MUSS), and listening and spoken language skills showed a
significant leap in 12 months duration post implantation. The report thus
highlights and correlates the significant progress in auditory and spoken
language skills of the child with congenital malformations to appropriate
auditory rehabilitation and intensive parental training.
PMID- 29937811
TI - Verification and validation of hearing aids: Opportunity not an obstacle.
AB - Verification and validation are objective and subjective measurements of hearing
aid function. Many studies have provided rationales for performing these
measurements as necessary for hearing aid practitioners to provide the highest
level of care. Several researchers have suggested that completing these
measurements as part of routine clinical care will reduce the number of return
visits, reduce the number of aids returned for credit, and increase patient
satisfaction. The purpose of this review article is to provide background, method
and rationale for practitioners to use these measurements to improve their
practice of hearing healthcare.
PMID- 29937810
TI - Current trends in outcome studies for children with hearing loss and the need to
establish a comprehensive framework of measuring outcomes in children with
hearing loss in China.
AB - Since the 1970s, outcome studies for children with hearing loss expanded from
focusing on assessing auditory awareness and speech perception skills to
evaluating language and speech development. Since the early 2000s, the multi
center large scale research systematically studied outcomes in the areas of
auditory awareness, speech-perception, language development, speech development,
educational achievements, cognitive development, and psychosocial development.
These studies advocated the establishment of baseline and regular follow-up
evaluations with a comprehensive framework centered on language development.
Recent research interests also include understanding the vast differences in
outcomes for children with hearing loss, understanding the relationships between
neurocognitive development and language acquisition in children with hearing
loss, and using outcome studies to guide evidence-based clinical practice. After
the establishment of standardized Mandarin language assessments, outcomes
research in Mainland China has the potential to expand beyond auditory awareness
and speech perception studies.
PMID- 29937812
TI - Enhanced auditory evoked potentials in musicians: A review of recent findings.
AB - Auditory evoked potentials serve as an objective mode for assessment to check the
functioning of the auditory system and neuroplasticity. Literature has reported
enhanced electrophysiological responses in musicians, which shows neuroplasticity
in musicians. Various databases including PubMed, Google, Google Scholar and
Medline were searched for references related to auditory evoked potentials in
musicians from 1994 till date. Different auditory evoked potentials in musicians
have been summarized in the present article. The findings of various studies may
support as evidences for music-induced neuroplasticity which can be used for the
treatment of various clinical disorders. The search results showed enhanced
auditory evoked potentials in musicians compared to non-musicians from brainstem
to cortical levels. Also, the present review showed enhanced attentive and pre
attentive skills in musicians compared to non-musicians.
PMID- 29937813
TI - Otolithic organ function in patients with profound sensorineural hearing loss.
AB - Profound sensorineural hearing loss (PSHL) is not uncommonly encountered in
otology. In clinics, there is a high incidence of otolithic damage in patients
with PSHL, but relevant reports are few. Sharing a continuous membranous
structure and similar receptor cell ultrastructures, the cochlea and vestibule
may be susceptible to the same harmful factors. Disorders of the inner ear may
result in a variety of manifestations, including vertigo, spatial disorientation,
blurred vision, impaired articulation, and hearing impairment. Considering the
diversity of clinical symptoms associated with PSHL with otolithic dysfunction,
it may be frequently misdiagnosed, and objective means of testing the function of
otolithic organs should be recommended for hearing-impaired patients. Vestibular
evoked myogenic potentials (VEMPs) via air-conducted sound are of great
importance for the diagnosis of otolithic function. Hearing devices such as
cochlear implants are commonly accepted treatments for PSHL, and early
identification and treatment of vestibular disorders may increase the success
rate of cochlear implantation. Therefore, it is necessary to increase awareness
of otolithic functional states in patients with PSHL.
PMID- 29937814
TI - A novel PIK3CD C896T mutation detected in bilateral sudden sensorineural hearing
loss using next generation sequencing: An indication of primary immunodeficiency.
AB - Objective: To investigate immune-related genetic background in bilateral sudden
sensorineural hearing loss (SSNHL). Case report and methods: The case is a 45
year-old man presenting with a 7-year history of bilateral profound SSNHL. Blood
biochemical testing demonstrated increased levels of total cholesterol (5.88
mmol/L). Tests for hepatitis B showed a positive antibody against the hepatitis B
core antigen. Complement C3 was below the normal value, and complement C4 and IgG
were in the lower range of normal values. CT images showed a normal inner ear and
vestibular aqueduct but round window membranous ossification on both sides. A
total number of 232 immune-associated genes were sequenced using the next
generation sequencing technique. Results: Mutations were detected in 5 genes,
including the phosphoinositide 3-kinase catalytic subunit delta (PIK3CD), caspase
recruitment domain-containing protein 9 (CARD9), complement factor H-related
(CFHR2), immunoglobulin lambda-like polypeptide 1 Protein (IGLL1), and
transmembrane channel-like gene family 8 (TMC8). In the PIK3CD gene, a C896T
substitute in exon 7 was detected. This mutation causes primary immunodeficiency
and is an autosomal dominant disease. Conclusion: The PIK3CD C896T mutation
responsible for primary immunodeficiency may contribute to the onset of bilateral
SSNHL with subsequent rapid progression.
PMID- 29937816
TI - Vestibular-evoked myogenic potentials in miniature pigs.
AB - Objective: To report detection of vestibular-evoked myogenic potentials (VEMPs)
in the miniature pig. Methods: Potentials evoked by 1000 Hz tone bursts were
recorded from neck extensor muscles and the masseter muscles in normal adult Bama
miniature pigs anesthetized with 3% pentobarbital sodium and Carbachol II.
Results: The latency of the first positive wave P from neck extensor muscles was
7.65 +/- 0.64 ms, with an amplitude of 1.66 +/- 0.34 uv and a rate of successful
induction of 75% at 80 dB SPL. The latency of potentials evoked from the masseter
muscles was 7.60 +/- 0.78 ms, with an amplitude of 1.31 +/- 0.28 uv and a rate
successful induction of 66% at 80 dB SPL. Conclusion: The latencies and
thresholds of VEMPs recorded from the neck extensor muscle and the masseter
muscle appear to be comparable in normal adult Bama miniature pigs, although the
amplitude recorded from the neck extensor muscle seems to be higher than that
from the masseter muscle. However, because of their usually relatively
superficial and easily accessible location, as well as their large volume and
strong contractions, masseter muscles may be better target muscles for recording
myogenic potentials.
PMID- 29937815
TI - Polymorphism of the 86th amino acid in CX26 protein and hereditary deafness.
AB - Objective: To investigate the membrane localization function of the CX26 protein
when its 86th amino acid is Thr, Ser or Arg, and its relations to deafness.
Methods: CX26-GFP protein with either Thr, Ser or Arg as the 86th amino acid was
expressed in mouse SGN cells via the GFP fusion type lenti-virus expression
system. The membrane localization of the fusion protein was observed under a
fluorescence microscope. Results: The mutated protein of CX26 T86S was localized
to cell membrane and form gap conjunction structures, showing no difference to
the wild type CX26 protein (with Thr as the 86th amino acid). However, the gap
conjunction structure disappeared when the mutation was CX26 T86A. Conclusion:
These results indicate that the CX26 T86R mutation may be a cause of hearing
loss, but CX26 T86S as a non-pathogenic polymorphism mutation does not affect
functions of the CX26 protein. The results are in accordance with the results of
clinical screening.
PMID- 29937817
TI - Temporal cues and the effect of their enhancement on speech perception in older
adults - A scoping review.
AB - Temporal envelope is a low frequency amplitude modulation conveying segmental and
suprasegmental information during speech perception. Unfortunately, we seldom
find ourselves in completely quiet listening environments and noise, commonly
found in the surrounding environment, obscures both the fine structure cues and
partly the temporal envelope cues in speech. Available temporal content of speech
emanating from noise is often enough to convey required information in normal
hearing individuals. However, the case is different in older adults (with and
without hearing loss) who lack such capabilities due to the impairment in
temporal processing. This calls attention of a researcher to delineate the
importance of temporal enhancement of speech in improving speech perception.
There are many temporal envelope strategies available in the literature, but each
one has its own lacunae. An envelope enhancement by a deep band modulation (DBM)
is found to be beneficial for those individuals who have had a temporal
processing impairment. The reason could be attributed to the 15 dB enhancement in
the temporal envelope bandwidth between 3 and 30 Hz, extracted from each channel,
which significantly increases the modulation depth such that masking of a
consonant by a vowel is minimized. Additionally, output of deep band modulated
speech is rescaled such that its duration increases and it provides relatively
easy access to the word of the lexicon. Thus, in the near future, with more
experiments related to DBM algorithm, it can be utilized in the rehabilitative
devices to lessen the impact of the temporal processing impairment.
PMID- 29937818
TI - Pre-attentive auditory discrimination skill in Indian classical vocal musicians
and non-musicians.
AB - Objective: To test for pre-attentive auditory discrimination skills in Indian
classical vocal musicians and non-musicians. Design: Mismatch negativity (MMN)
was recorded to test for pre-attentive auditory discrimination skills with a pair
of stimuli of /1000 Hz/ and /1100 Hz/, with /1000 Hz/ as the frequent stimulus
and /1100 Hz/ as the infrequent stimulus. Onset, offset and peak latencies were
the considered latency parameters, whereas peak amplitude and area under the
curve were considered for amplitude analysis. Study sample: Exactly 50
participants, out of which the experimental group had 25 adult Indian classical
vocal musicians and 25 age-matched non-musicians served as the control group,
were included in the study. Experimental group participants had a minimum
professional music experience in Indian classic vocal music of 10 years. However,
control group participants did not have any formal training in music. Results:
Descriptive statistics showed better waveform morphology in the experimental
group as compared to the control. MANOVA showed significantly better onset
latency, peak amplitude and area under the curve in the experimental group but no
significant difference in the offset and peak latencies between the two groups.
Conclusion: The present study probably points towards the enhancement of pre
attentive auditory discrimination skills in Indian classical vocal musicians
compared to non-musicians. It indicates that Indian classical musical training
enhances pre-attentive auditory discrimination skills in musicians, leading to
higher peak amplitude and a greater area under the curve compared to non
musicians.
PMID- 29937819
TI - Human otoacariasis: Demographic and clinical outcomes in patients with ear-canal
ticks and a review of literature.
AB - Introduction: Otoacariasis is a rare infestation of the ear canal, which affects
the quality of life especially in rural areas. Different types of ticks and mites
may cause otoacariasis. Although treatment of otoacariasis is simple, diseases
transmitted through ticks and mites should be considered during diagnosis and
treatment. Both local and systemic signs and symptoms of such diseases should be
followed up.A literature review was conducted in PubMed using the following
terms: "otoacariasis," "ticks," "mites," and "outer ear canal infestations."
Demographic, radiologic, and treatment options were discussed. Treatment hints
and pitfalls were also discussed with the literature review. Conclusion: In this
paper, we describe otoacariasis in humans and discuss the appropriate
interventions.
PMID- 29937820
TI - Trimethyltin-induced cochlear degeneration in rat.
AB - Trimethyltin (TMT) is an occupational and environmental health hazard behaving as
a potent neurotoxin known to affect the central nervous system as well as the
peripheral auditory system. However, the mechanisms underlying TMT-induced
ototoxicity are poorly understood. To elucidate the effects of TMT on the
cochlea, a single injection of 4 or 8 mg/kg TMT was administered
intraperitoneally to adult rats. The compound action potential (CAP) threshold
was used to assess the functional status of the cochlea and histological
techniques were used to assess the condition of the hair cells and auditory nerve
fibers. TMT at 4 mg/kg produced a temporary CAP threshold elevation of 25-60 dB
that recovered by 28 d post-treatment. Although there was no hair cell loss with
the 4 mg/kg dose, there was a noticeable loss of auditory nerve fibers
particularly beneath the inner hair cells. TMT at 8 mg/kg produced a large
permanent CAP threshold shift that was greatest at the high frequencies. The CAP
threshold shift was associated with the loss of outer hair cells and inner hair
cells in the basal, high-frequency region of the cochlea, considerable loss of
auditory nerve fibers and a significant loss of spiral ganglion neurons in the
basal turn. Spiral ganglion neurons showed evidence of soma shrinkage and nuclear
condensation and fragmentation, morphological features of apoptotic cell death.
TMT-induced damage was greatest in the high-frequency, basal region of the
cochlea and the nerve fibers beneath the inner hair cells were the most
vulnerable structures.
PMID- 29937821
TI - Label-free visualization of cholesteatoma in the mastoid and tympanic membrane
using CARS microscopy.
AB - Objective: The present study aimed to evaluate the possibility of using coherent
anti-Stokes Raman spectroscopy (CARS) microscopy to determine the specific
molecular morphology of cholesteatoma by detecting the natural vibrational
contrast of the chemical bonds without any staining. Materials and methods:
Specimens from the mastoid and tympanic membrane with and without cholesteatoma
were analyzed using CARS microscopy, two-photon excited fluorescence (TPEF)
microscopy, and the second harmonic generation (SHG) microscopy. Results: In
cholesteatoma tissues from the mastoid, a strong resonant signal at 2845 cm-1 was
observed by CARS, which indicated the detection of the CH2 hydro-carbon lipid
bonds that do not generate visible signals at 2940 cm-1 suggestive of CH3 bonds
in amino acids. A strong resonant signal at 2940 cm-1 appeared in an area of the
same specimen, which also generated abundant signals by TPEF and SHG microscopy
at 817 nm, which was suggestive of collagen. In the tympanic membrane specimen
with cholesteatoma, a strong resonant signal with corrugated morphology was
detected, which indicated the presence of lipids. A strong signal was detected in
the tympanic membrane with chronic otitis media using TPEF/SHG at 817 nm, which
indicated collagen enrichment. The CARS and TPEF/SHG images were in accordance
with the histology results. Conclusion: These results suggest the need to develop
a novel CARS microendoscope that can be used in combination with TPEF/SHG to
distinguish cholesteatoma from inflammatory tissues.
PMID- 29937822
TI - A screening analysis of the GJB2 c.176 del 16 mutation responsible for hereditary
deafness in a Chinese family.
AB - Objective: To determine whether a new-born child from a family carrying a
deafness gene needs cochlear implantation to avoid dysphonia by screening and
sequencing a deafness-related gene. Results: Both screening and sequencing
results confirmed that the new born child had a normal GJB2 gene despite the fact
that she has a brother suffering from hearing loss triggered by an allelic GJB2
c.176 del 16 mutation. We cloned the GJB2 genes derived from their respective
blood genomic DNA into GFP fused plasmids and transfected those plasmids into the
293T cell line to test for gene function. While the mutated GJB2 gene (GJB2 c.176
del 16) of her deaf brother was found to be unable to form the gap junction
structure between two adjacent cells, the baby girl's GJB2 gene ran into no such
problems. Conclusion: The screening and sequencing as well as the GJB2 gene
function tests invariably showed results consistent with the ABR tested hearing
phenotype, which means that the child, with a normal wild type GJB2 gene, does
not need early intervention to prevent her from developing hearing loss and
dysphonia at a later stage in life.
PMID- 29937823
TI - Vestibular-evoked myogenic potentials recorded from miniature pigs and rats.
AB - Objective: To report vestibular evoked myogenic potentials from different
recording sites (neck extensor or masseter muscles) in miniature pigs and rats.
Methods: Potentials were recorded using 1000 Hz tone bursts from the neck
extensor muscle or masseter muscle in normal adult Bama miniature pigs and rats
anesthetized with 3% pentobarbital sodium and Sumianxin II. Results: At 80 dB
SPL, the first positive wave (P wave) of VEMPs was recognizable in 58% of rats
with a latency of 6.45 +/- 0.23 ms and an amplitude of 1.45 +/- 0.49 MUV when
recorded from the neck extensor muscle, and in 50% of rats with a latency of 6.38
+/- 0.34 ms and an amplitude of 1.57 +/- 0.35 MUV when recorded from the masseter
muscle. In miniature pigs, at the same stimulus intensity, P wave was
recognizable in 58% of the animals with a latency of 7.65 +/- 0.64 ms and an
amplitude of 1.66 +/- 0.34 MUV when recorded from the neck extensor muscle, and
in 50% of the animals with a latency of 7.65 +/- 0.64 ms and an amplitude of 0.31
+/- 0.28 MUV when recorded from the masseter muscle. Conclusion: VEMP can be
induced from both neck extensor and masseter muscles in the miniature pig and
rat. For a given species, the site of recording affects P wave induction rate and
amplitude but not latency. Consistency and repeatability analysis suggests that
the masseter muscle is a better recording site in miniature pigs while the
cervical extensor is a better recording site in rats. For a given recording site,
both latency and amplitude of the P wave are slightly greater in miniature pigs
than in rats.
PMID- 29937825
TI - Contemporary solutions for patients with microtia and congenital aural atresia -
Hong Kong experience.
AB - Managing microtia patients is always a challenge. Multidisciplinary approach,
good family support, well established doctor-patient relationship and well
organised patient-support groups are the essential elements for success. With the
advancement of implantable hearing devices, more options will be available for
the microtia patients. Otologists play a leading role in the whole management
process. They not only provide proper guidance to the patients in choosing the
correct path of the treatment, but also play a key role in organising and
maintaining a cost-effective multidisciplinary rehabilitation team for the
microtia patients.
PMID- 29937824
TI - Ototoxic effects and mechanisms of loop diuretics.
AB - Over the past two decades considerable progress has been made in understanding
the ototoxic effects and mechanisms underlying loop diuretics. As typical
representative of loop diuretics ethacrynic acid or furosemide only induces
temporary hearing loss, but rarely permanent deafness unless applied in severe
acute or chronic renal failure or with other ototoxic drugs. Loop diuretic induce
unique pathological changes in the cochlea such as formation of edematous spaces
in the epithelium of the stria vascularis, which leads to rapid decrease of the
endolymphatic potential and eventual loss of the cochlear microphonic potential,
summating potential, and compound action potential. Loop diuretics interfere with
strial adenylate cyclase and Na+/K+-ATPase and inhibit the Na-K-2Cl cotransporter
in the stria vascularis, however recent reports indicate that one of the earliest
effects in vivo is to abolish blood flow in the vessels supplying the lateral
wall. Since ethacrynic acid does not damage the stria vascularis in vitro, the
changes in Na+/K+-ATPase and Na-K-2Cl seen in vivo may be secondary effects
results from strial ischemia and anoxia. Recent observations showing that renin
is present in pericytes surrounding stria arterioles suggest that diuretics may
induce local vasoconstriction by renin secretion and angiotensin formation. The
tight junctions in the blood-cochlea barrier prevent toxic molecules and
pathogens from entering cochlea, but when diuretics induce a transient ischemia,
the barrier is temporarily disrupted allowing the entry of toxic chemicals or
pathogens.
PMID- 29937826
TI - Inner ear barriers to nanomedicine-augmented drug delivery and imaging.
AB - There are several challenges to inner ear drug delivery and imaging due to the
existence of tight biological barriers to the target structure and the dense bone
surrounding it. Advances in imaging and nanomedicine may provide knowledge for
overcoming the existing limitations to both the diagnosis and treatment of inner
ear diseases. Novel techniques have improved the efficacy of drug delivery and
targeting to the inner ear, as well as the quality and accuracy of imaging this
structure. In this review, we will describe the pathways and biological barriers
of the inner ear regarding drug delivery, the beneficial applications and
limitations of the imaging techniques available for inner ear research, the
behavior of engineered nanomaterials in inner ear applications, and future
perspectives for nanomedicine-based inner ear imaging.
PMID- 29937827
TI - Intra-operative hearing monitoring methods in middle ear surgeries.
AB - Hearing loss is a condition affecting millions of people worldwide. Conductive
hearing loss (CHL) is mainly caused by middle ear diseases. The low frequency
area is the pivotal part of speech frequencies and most frequently impaired in
patients with CHL. Among various treatments of CHL, middle ear surgery is
efficient to improve hearing. However, variable success rates and possible needs
for prolonged revision surgery still frustrate both surgeons and patients.
Nowadays, increasing numbers of researchers explore various methods to monitor
the efficacy of ossicular reconstruction intraoperatively, including
electrocochleography (ECochG), auditory brainstem response (ABR), auditory steady
state response (ASSR), distortion product otoacoustic emissions (DPOAE),
subjective whisper test, and optical coherence tomography (OCT). Here, we
illustrate several methods used clinically by reviewing the literature.
PMID- 29937828
TI - Auditory neuropathy in a patient with hemochromatosis.
AB - Objective: To evaluate the auditory function of an individual with genetically
confirmed hemochromatosis. Methods: A 57 year old male with mildly impaired sound
detection thresholds underwent a range of behavioural, electroacoustic and
electrophysiologic assessments. These included the recording of otoacoustic
emissions and auditory brainstem responses, measurement of monaural temporal
resolution and evaluation of binaural speech processing. Findings for this
patient were subsequently compared with those of 80 healthy controls with similar
audiometric thresholds. Results: The patient showed the three cardinal features
of auditory neuropathy, presenting with evidence of normal cochlear outer hair
cell function, disrupted neural activity in the auditory nerve/brainstem and
impaired temporal processing. His functional hearing ability (speech perception)
was significantly affected and suggested a reduced capacity to use localization
cues to segregate signals in the presence of background noise. Conclusion: We
present the first case of an individual with hemochromatosis and auditory
neuropathy. The findings for this patient highlight the need for careful
evaluation of auditory function in individuals with the disorder.
PMID- 29937829
TI - Evaluation of ocular and cervical vestibular evoked myogenic potentials in a
conductive hearing loss model.
AB - Objective: To investigate the effects of conductive hearing loss (CHL) on
vestibular evoked myogenic potentials (VEMPs) using a simulated CHL model, and to
provide the basis for future studies. Methods: Twenty-one healthy subjects were
recruited in this study. We measured ocular VEMPs (oVEMPs) and cervical VEMPs
(cVEMPs) in these subjects by air-conduction sound (ACS) stimulation. CHL was
simulated later by blocking the right external auditory canal with a soundproof
earplug to evaluate its impacts on VEMPs. Subjects' responses before simulated
CHL served as the control, and were compared to their responses following
simulated CHL. Results: oVEMPs following simulated CHL showed decreased response
rate, elevated thresholds, attenuated amplitudes and prolonged N1 latencies
compared with those before simulated CHL, and the differences were statistically
significant. Similarly, cVEMPs following simulated CHL also showed decreased
response rate, elevated thresholds and attenuated amplitudes, with prolonged P1
latencies compared with those before simulated CHL, although only differences in
response rate, threshold and amplitude were significant. Conclusions: Conductive
hearing loss affects the response rate and other response parameters in oVEMPs
and cVEMPs.
PMID- 29937830
TI - After cochlear implantation: Complications related to flap around implants.
AB - Objective: To report complications related to flap around implants after cochlear
implantation, possible causes of such complications and treatments. Methods and
material: We performed a retrospective analysis of children in whom complications
related to flap around implants occurred after undergoing cochlear implantation
in our department from 2005 to 2016. Results: Complications among 1500 cochlear
implantation (CI) recipients by the same surgeon included hematoma (n = 20) and
seroma around implants (n = 15), of which most (n = 10) recovered in 2 weeks
after effective drainage, utility of antibiotics and pressure dressing, but 5
developed flap necrosis and had to undergo contralateral re-implantation. Four
patients developed abscess around implants, of whom 2 recovered after 2 weeks of
drainage, gentamicin irrigation and use of antibiotics, but 2 patients ended up
with flap necrosis and had to receive contralateral reimplantation. Conclusions:
Immediate drainage, pressure dressing and antibiotics can be used to effectively
control seroma around implants. For seroma lasting for more than two weeks
without improvement, surgical drainage may be need.
PMID- 29937831
TI - Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity.
AB - Aminoglycosides (AmAn) are widely used for their great efficiency against gram
negative bacterial infections. However, they can also induce ototoxic hearing
loss, which has affected millions of people around the world. As previously
reported, individuals bearing mitochondrial DNA mutations in the 12S rRNA gene,
such as m.1555A>G and m.1494C>T, are more prone to AmAn-induced ototoxicity.
These mutations cause human mitochondrial ribosomes to more closely resemble
bacterial ribosomes and enable a stronger aminoglycoside interaction.
Consequently, exposure to AmAn can induce or worsen hearing loss in these
individuals. Furthermore, a wide range of severity and penetrance of hearing loss
was observed among families carrying these mutations. Studies have revealed that
these mitochondria mutations are the primary molecular mechanism of genetic
susceptibility to AmAn ototoxicity, though nuclear modifier genes and
mitochondrial haplotypes are known to modulate the phenotypic manifestation.
PMID- 29937832
TI - Clinically relevant human temporal bone measurements using novel high-resolution
cone-beam CT.
AB - Objective: To test the feasibility of measuring fine temporal bone structures
using a newly established cone-beam computed tomography (CBCT) system. Materials
and methods: Six formalin-fixed human cadaver temporal bones were imaged using a
high-resolution CBCT system that has 900 frames and copper + aluminum filtration.
Fine temporal bone structures, including those of the facial nerve canal and
vestibular structures, were identified and measured. Results: The fine structures
of the middle ear, including the tympanic membrane, tendon of the tensor tympani,
cochleariform process of the semicanal of the tensor tympani, pyramidal eminence,
footplate of the stapes, full path of the facial nerve within the temporal bone,
supralabyrinthine space, semicircular canals, pathway of the subarcuate canal,
and full path of the vestibular aqueduct, were clearly demonstrated. The
vestibular aqueduct has a midpoint width of 0.4 +/- 0.0 mm and opercular width of
0.5 +/- 0.1 mm (mean +/- SD). The length of the internal acoustic meatus was 10.6
+/- 1.2 mm (mean +/- SD), and the diameter of the internal acoustic meatus was
3.7 +/- 0.3 mm (mean +/- SD). Conclusion: This novel high-resolution CBCT system
has potentially broad applications in the diagnosis of inner ear disease and in
monitoring associated pathological changes, surgical planning, navigation for the
ear surgery, and temporal bone training.
PMID- 29937833
TI - Suprathreshold compound action potential amplitude as a measure of auditory
function in cochlear implant users.
AB - Electrically evoked compound action potential (eCAP) amplitudes elicited at
suprathreshold levels were assessed as a measure of the effectiveness of cochlear
implant (CI) stimulation. Twenty-one individuals participated; one was excluded
due to facial stimulation during eCAP testing. For each participant, eCAPs were
elicited with stimulation from seven electrodes near the upper limit of the
individual's electrical dynamic range. A reduced-channel CI program was created
using those same seven electrodes, and participants performed a vowel
discrimination task. Consistent with previous reports, eCAP amplitudes varied
across tested electrodes; the profiles were unique to each individual. In 6
subjects (30%), eCAP amplitude variability was partially explained by the
impedance of the recording electrode. The remaining amplitude variability within
subjects, and the variability observed across subjects could not be explained by
recording electrode impedance. This implies that other underlying factors, such
as variations in neural status across the array, are responsible. Across-site
mean eCAP amplitude was significantly correlated with vowel discrimination scores
(r2 = 0.56). A single eCAP amplitude measured from the middle of the array was
also significantly correlated with vowel discrimination, but the correlation was
weaker (r2 = 0.37), though not statistically different from the across-site mean.
Normalizing each eCAP amplitude by its associated recording electrode impedance
did not improve the correlation with vowel discrimination (r2 = 0.52). Further
work is needed to assess whether combining eCAP amplitude with other measures of
the electrode-neural interface and/or with more central measures of auditory
function provides a more complete picture of auditory function in CI recipients.
PMID- 29937834
TI - Electrocochleographic recording in Asian adults: Preliminary normative data and
demographic analyses.
AB - Objective: Electrocochleography (ECochG) is valuable to diagnose Meniere's
disease objectively. The aim of the present study was to provide preliminary
normative data for ECochG among Asian adults. The influences of ethnicity (Malay
versus Chinese) and gender on ECochG results were also studied. Methods: Twenty
two Malay adults (10 men and 12 women) and twenty Chinese participants (10 men
and 10 women) aged between 20 and 49 years participated in this study.
Extratympanic ECochG (ET-ECochG) was recorded according to standard non-invasive
procedure. Summating potential (SP) amplitude, action potential (AP) amplitude
and SP/AP ratio were analyzed accordingly. Results: ET-ECochG results were found
to be comparable between left and right ears (p > 0.05). No notable differences
in ET-ECochG results were found between Malay and Chinese groups (p > 0.05). No
significant influence of gender on ET-ECochG outcomes was also noted (p > 0.05).
The derived normative data for Asian adults (84 ears) are consistent with
previous reports. Conclusion: The present study provides preliminary normative
data for ET-ECochG among Asian adults. The ECochG components do not appear to be
influenced by either ethnicity or gender. The derived normative data can be used
for clinical applications and as the reference for future studies involving Asian
population.
PMID- 29937835
TI - Auditory deprivation modifies the expression of brain-derived neurotrophic factor
and tropomyosin receptor kinase B in the rat auditory cortex.
AB - The development and plasticity of central auditory system can be influenced by
the change of peripheral neuronal activity. However, the molecular mechanism
participating in the process remains elusive. Brain-derived neurotrophic factor
(BDNF) binding with its functional receptor tropomyosin receptor kinase B (TrkB)
has multiple effects on neurons. Here we used a rat model of auditory deprivation
by bilateral cochlear ablation, to investigate the changes in expression of BDNF
and TrkB in the auditory cortex after auditory deprivation that occurred during
the critical period for the development of central auditory system. Reverse
transcription-quantitative polymerase chain reaction (RT-qPCR) and
immunohistochemistry methods were adopted to detect the mRNA and protein
expression levels of BDNF and TrkB in the auditory cortex at 2, 4, 6 and 8 weeks
after surgery, respectively. The change in the expression of BDNF and TrkB mRNAs
and proteins followed similar trend. In the bilateral cochlear ablation groups,
the BDNF-TrkB expression level initially decreased at 2 weeks but increased at 4
weeks followed by the reduction at 6 and 8 weeks after cochlear removal, as
compared to the age-matched sham control groups. In conclusion, the BDNF-TrkB
signaling is involved in the plasticity of auditory cortex in an activity
dependent manner.
PMID- 29937836
TI - A child with severe inner ear malformations with favorable hearing utilization
and balance functions after wearing hearing aids.
AB - Infants with congenital deafness caused by severe bilateral inner ear
malformations frequently suffer from severe hearing loss and poor balance.
Unfortunately, the use of hearing aids is usually ineffective in recovering
hearing, necessitating cochlear implants. We report a case of a 6-year-old boy
with congenital deafness and bilateral inner ear malformations (right side,
incomplete partition type I [IP-I]; left side, common cavity deformity). Hearing
aids had a remarkable effect in this patient, enabling sufficient and favorable
hearing recovery such as to allow the patient to engage in daily conversations.
Per-rotatory nystagmus was recorded on an electronystagmogram for both right and
left rotations in a damped rotational chair test. It is rare for deaf children
with severe bilateral inner ear malformation to demonstrate favorable development
in hearing and good equilibrium function. Our findings suggest that auditory
vestibular hair cells in this patient may have been partially preserved despite
IP-I in the right ear and common cavity deformity of the left ear.
PMID- 29937838
TI - The potential of miR-183 family expression in inner ear for regeneration,
treatment, diagnosis and prognosis of hearing loss.
AB - miRNA-183 family, in normal biology, is expressed in a harmonious and stable
manner in the neurosensory organs and cells. Studies have also shown that miRNA
183 family, in different pathways, affects the neurosensory development,
maintenance, survival and function. In addition, it has potential neuroprotective
effects in response to neurosensory destructive stimulations. miRNA-96 mutation
causes hereditary deafness in humans and mice, and therefore affects the inner
ear activity and its maintenance. Certain roles have been identified for miR-96
in the maintenance and function of the inner ear. The comparison of the target
genes of family-183 in transcriptomes of newborn and adult hair cells shows that
hundreds of target genes in this family may affect development and maintenance of
the ears. Identifying the genes that are regulated by miRNA-183 family provides
researchers with important information about the complex development and
environmental regulation of the inner ear, and can offer new approaches to the
maintenance and regeneration of hair cells and auditory nerve.
PMID- 29937839
TI - Endoscopic tympanoplasty.
AB - Middle ear surgery is usually performed using a surgical microscope. Initially,
in otorhinolaryngology practice, endoscopes were used for paranasal sinus
surgeries. It was only later that they were applied in the area of otology. In
otologic surgeries, endoscopes were first used to visualize the middle ear,
before being used to assist with visualization of instruments during
cholesteatoma surgeries, although they are still not used alone in various
otologic surgeries. As in other surgical fields, there is also a trend towards
minimally invasive intervention in the field of otorhinolaryngology. Smaller
incisions performed under the guidance of endoscopes are preferred over
conventional large incisions. Using this approach, improved outcomes can be
achieved and postoperative morbidities can be reduced. In addition, the outcomes
of grafts performed using the endoscopic approach are similar to that achieved by
the microscopic approach. Therefore, endoscopic ear surgery implementations are
becoming increasingly popular.
PMID- 29937837
TI - Histone deacetylases in hearing loss: Current perspectives for therapy.
AB - Hearing loss is one of the most frequent health issues in industrialized
countries. The pathogenesis and molecular mechanisms of hearing loss are still
unclear. Histone deacetylases (HDACs) are emerging as key enzymes in many
physiological processes, including chromatin remodeling, regulation of
transcription, DNA repair, metabolism, genome stability and protein secretion.
Recent studies indicated that HDACs are associated with the development and
progression of hearing loss. Dysfunction of HDACs could promote the oxidative
stress and aging in the inner ear. In light of considering the current stagnation
in the development of therapeutic options, the need for new strategies in the
treatment of hearing loss has never been so pressing. In this review, we will
summarize the reported literatures for HDACs in hearing loss and discuss how HDAC
family members show different performances for the possibility of process of
diseases development. The possibility of pharmacological intervention on hearing
loss opens a novel path in the treatment of hearing loss.
PMID- 29937840
TI - Normative data for TM electrocochleography measures.
AB - Objective: Establish normative data for tympanic electrocochleography (TM ECochG)
parameters in normal hearing adults without Meniere's disease's (MD) symptoms.
Describe TM ECochG variables that help to distinguish normal from MD ears.
Material and methods: We enrolled 100 subjects (N = 200 ears), 59 females, aged
between 19 and 71 years from 09/2010 to 04/2014. Inclusion criteria: normal
otomicroscopy, hearing thresholds <=25 dB nHL from 250 to 4000 Hz, normal
tympanogram, no symptoms of MD according to the AAO-HNS 1995 criteria and
Gibson's score <7. We excluded subjects with dizziness, aural fullness or other
symptoms of endolymphatic hydrops. The following parameters were analyzed: SP/AP
amplitude ratio, SP/AP area ratio and the difference between AP latency with
rarefaction and condensation stimuli. Results: There was no significant
difference between right and left ears (Intraclass correlation coefficient <
0.6). SP/AP amplitude ratio varied between 0.084 and 0.356 and SP/AP area ratio
between 0.837 and 1.671 (percentiles 5 and 95). The AP latency difference to
rarefaction and condensation clicks was between 0.0 and 0.333 ms. Conclusion:
Normative data for TM ECochG parameters were established in 100 normal hearing
subjects without MD. These data can be used to distinguish normal from
pathological findings and in follow-up of MD patients.
PMID- 29937841
TI - Disagreement in middle ear volume estimation between tympanometry and three
dimensional volume reconstruction in the context of tympanic membrane
perforation.
AB - Introduction: Middle ear volume (MEV) is a clinically relevant parameter across
middle ear diseases. MEV values between these techniques have never before been
tested for agreement in ears with perforated tympanic membranes (TMs). Methods:
Middle ears were identified from 36 patients ranging 18-89 years of age with TM
perforations who underwent tympanometry and temporal bone computed tomography
(CT) between 2005 and 2015. MEVs calculated by both tympanometry and three
dimensional volume reconstruction (3DVR) were analyzed for agreement using Bland
Altman plots. The differences between tympanometric and 3DVR MEV values for each
given middle ear were characterized across MEV quartiles (1 = smallest; 4 =
largest) and across increasing states of middle ear disease using Kruskal-Wallis
and Wilcoxon testing with Bonferroni correction. Results: Bland Altman plots
demonstrated significant disagreement between MEV measurement techniques.
Differences between tympanometric (T) and 3DVR MEV values were significantly
greater with increasing average (i.e. (T+3DVR)/2)) MEV per linear regression (p <
0.0001). Significance was demonstrated between fourth and first average MEV
quartiles (p = 0.0024), fourth and second quartiles (p = 0.0024), third and first
quartiles (p = 0.0048), and third and second quartiles (p = 0.048). Absolute MEV
difference was not significantly different across varying states of middle ear
disease (p = 0.44). Conclusion: Statistically and clinically significant
disagreement was demonstrated between tympanometric and 3DVR MEV values. Studies
that vary in MEV estimation techniques may be expected to demonstrate
significantly different results. These preliminary results suggest that
clinicians should endeavor to seek further confirmation when interpreting high
tympanometric MEV values.
PMID- 29937842
TI - Value of section plane, MPR, and 3D-CTVR techniques in the fine differential
diagnosis of ossicular chain in the case of conductive hearing loss with intact
tympanic membrane.
AB - Aim: To assess the quality of high-resolution CT section planes (HRCT), multi
planar reformation (MPR) and 3-dimensional volume rendered computer tomography
(3D-CTVR) were here used in the fine differential diagnosis of ossicular chain in
the case of conductive hearing loss with intact tympanic membrane. Methods: Here,
17 cases of otosclerosis and 22 cases of ossicular chain deformity were selected.
All patients had normal external ear canals, intact tympanic membranes,
conductive hearing loss, type A tympanograms, and negative Gelle's tests. The
respective radiological reports of the status of the ossicles via 3 protocols
were compared to surgical findings. The quantitative assessments of the
representation of different segments of the ossicular chain were based on a 3
point scoring system. Results: MPR and CTVR imaging both showed the integrity of
whole ossicular chain well. MPR and CTVR imaging were found to be superior to
section planes with respect to showing the superstructure of the stapes and
malformations (P > 0.05). Conclusion: CTVR and MPR imaging were found to be
better able to show the whole ossicular chain in the conductive hearing loss with
normal tympanic membranes. Furthermore, the use of these techniques can have
profound contributive value in the differential diagnosis of otosclerosis and
ossicular chain absence or malformation.
PMID- 29937843
TI - Speech, language, and hearing function in twins with Alport syndrome: A seven
year retrospective case report.
AB - Alport syndrome is an X-linked syndrome that results in nephritis, renal failure,
sensorineural hearing loss, and eye deficits. As a result of sensorineural
hearing loss, these individuals are likely to experience difficulties in the area
of speech and language. While studies in the past have examined the speech and
language characteristics of children with syndromic sensorineural hearing loss,
to our knowledge there are no previous studies to have documented the speech and
language characteristics of these children on a long-term basis. The current
study addresses this limitation by reporting speech, language, hearing, and
function of twin brothers with X-linked Alport syndrome across a seven-year
period. Information was collected by examining the medical records of the
participants as well as through a verbal interview with the participants'
guardian. Results revealed that the participants' hearing abilities gradually
deteriorated over the seven-year period which affected their speech and language
development as well. The kidney function tests revealed significant presence of
hematuria (blood in the urine) as well as proteinuria (protein in the urine)
suggesting chronic kidney dysfunction. This longitudinal study demonstrates the
functional relationship between the kidneys and the cochlea, although they appear
to be independent of one another. As individuals with Alport syndrome exhibit
systemic complications, interdisciplinary collaboration is essential among health
care providers including audiologists, speech-language pathologists,
nephrologists, and ophthalmologist to promote evidence-based practice.
PMID- 29937844
TI - Auditory perceptual efficacy of nonlinear frequency compression used in hearing
aids: A review.
AB - Many patients with sensorineural hearing loss have a precipitous high-frequency
loss with relatively good thresholds in the low frequencies. This present paper
briefly introduces and compares the basic principles of four types of frequency
lowering algorithms with emphasis on nonlinear frequency compression (NLFC). A
review of the effects of the NLFC algorithm on speech and music perception and
sound quality appraisal is then provided. For vowel perception, it seems that the
benefits provided by NLFC are limited, which are probably related to the
parameter settings of the compression. For consonant perception, several studies
have shown that NLFC provides improved perception of high-frequency consonants
such as /s/ and /z/. However, a few other studies have demonstrated negative
results in consonant perception. In terms of sentence recognition, persistent use
of NLFC might provide improved performance. Compared to the conventional
processing, NLFC does not alter the speech sound quality appraisal and music
perception as long as the compression setting is not too aggressive. In the
subsequent section, the relevant factors with regard to NLFC settings, time
course of acclimatization, listener characteristics, and perceptual tasks are
discussed. Although the literature shows mixed results on the perceptual efficacy
of NLFC, this technique improved certain aspects of speech understanding in
certain hearing-impaired listeners. Little research is available on speech
perception outcomes in languages other than English. More clinical data are
needed to verify the perceptual efficacy of NLFC in patients with precipitous
high-frequency hearing loss. Such knowledge will help guide clinical
rehabilitation of those patients.
PMID- 29937845
TI - Retraction pocket excision with cartilage grafting as a preventive surgery for
cholesteatoma.
AB - Aims: The goal of the present study is to summarize our experience on surgical
management of retraction pockets (RP) as a preventive tool against
cholesteatomas. Methods: Twenty-five ears have been followed up for a mean period
of 6.16 +/- 4.35 years (from 1 to 17 years). The sample presented a mean age of
47.56 +/- 19.11 years (from 16 to 73 years). All patients underwent cartilage
graft surgery. Furthermore 10 (40%) underwent tympanoplasty (TPL) type I, 14
(56%) TPL type II and 1 (4%) TPL type V. Results: Eleven ears (44%) showed
cholesteatoma: all these cases were stage III according to Charachon staging, and
stage IV or V according to Gersdorff classification. Twelve patients (48%) showed
erosion of the ossicular chain. Of these, five were associated with cholesteatoma
and seven only with retraction. The recurrence rate of cholesteatoma was 12%.
None of the patients with a stage II or III RP (according to Gersdorff
classification) developed cholesteatoma. The recurrence of RP was 0%.In regards
to literature review, seven references were selected. These studies showed a
success rate ranging from 79.1% to 88%, while recurrences of RP varied from 6.4%
to 13%. Only one study specified a recurrence rate of cholesteatoma of 28%.
Conclusions: Surgical treatment of stages II and III RP is an effective tool to
prevent cholesteatoma formation. The presence of keratin accumulation and
cholesteatoma at the RP (stages IV and V, according to Gersdorff) are the real
predictors of poor prognosis.
PMID- 29937846
TI - Intratympanic corticosteroids in Meniere's disease: A mini-review.
AB - This article reviews the effectiveness of intratympanic corticosteroids for
vertigo control in Meniere's disease at 2-years follow-up according to the
guidelines expressed by the American Academy of Otolaryngology-Head & Neck
Surgery. Despite the increased use of intratympanic corticosteroids for vertigo
control in Meniere's disease there is debate as to their effectiveness,
particularly compared to gentamicin. Even so, after just a single course of
injections, corticosteroids can reliably provide complete vertigo control (Class
A) at 2-years in about 50% of cases as indicated in a recent double-blind
randomized controlled clinical trial (Patel et al., 2016). But the effectiveness
of intratympanic corticosteroids truly increases when treatment is provided 'as
needed', whereby complete vertigo control is established in up to 91% of cases.
On the basis of available literature, there is good evidence to recommend the use
of intratympanic steroid treatment for vertigo control in Meniere's disease, but
patients must be monitored for non-response. The rationale for treating patients
as-needed and the possible reasons for corticosteroid non-response are discussed.
PMID- 29937847
TI - The anatomic determinants of conductive hearing loss secondary to tympanic
membrane perforation.
AB - Objectives: Recent studies have introduced middle ear volume (MEV) as a novel
determinant of perforation-induced conductive hearing loss (CHL) in a mechanism
driven by trans-tympanic membrane pressure differences. The primary aims of this
preliminary report are to: 1) correlate CHL with perforation size; 2) describe
the relationship between CHL and MEV; and 3) compare CHL across a range of
cholesteatoma involvement. Design: A retrospective pilot study was performed in
31 subjects with audiometry indicative of conductive hearing loss, temporal bone
CT scans, and no prior middle ear surgery. Perforation size and MEV were analyzed
with respect to CHL in a cohort of 10 perforated ears with no cholesteatoma. CHLs
were compared in 3 groups defined by extent of cholesteatoma involvement.
Results: Ears with large and small perforations showed mean ABG values of 32.0 +/
15.7 dB and 16.0 +/- 16.4 dB, respectively. A direct relationship was observed
between MEV and CHL for ears with large perforations across all frequencies,
whereas this relationship for small perforations was frequency-dependent.
Finally, a statistically significant increase in CHL was found across ears with
increasing cholesteatoma involvement at 1000 Hz (chi2(2) = 9.786, p = 0.008),
2000 Hz (chi2(2) = 8.455, p = 0.015), and 4000 Hz (chi2(2) = 8.253, p = 0.016).
Conclusions: These pilot data suggest that greater perforation-induced conductive
hearing losses may be associated with larger perforation sizes and cholesteatoma.
The correlation between MEV and CHL may require additional study.
PMID- 29937848
TI - Auditory symptoms and psychological characteristics in adults with auditory
processing disorders.
AB - Most adults with auditory processing disorder (APD) often have trouble at work.
It is possible that these listening problems in adults with APD influence their
mental health. Thus, we have to take the subject's personality and mental status
into consideration when supporting subjects with APD. However, studies on APD in
adults are comparatively rare. In this study, we aimed to evaluate the
relationships between the results of auditory tests, APD symptoms, and
psychological status in subjects with APD. This study included 22 adults who
complained of listening problems in everyday life, and they underwent auditory
processing tests and were questioned regarding their psychological
characteristics. From the results of the auditory processing tests, all subjects
showed low scores on at least one test; therefore, they were suspected of having
APD. Especially, the scores were low on the auditory memory test. Furthermore,
subjects with APD show relatively similar psychological characteristics to each
other. However, there was no significant relationship between the results of the
auditory processing tests and psychological characteristics. We have to take
notice of a subject's psychological state when they perceive their listening
difficulties as a large-scale problem and feel anxious as a result. For this
purpose, we should take psychological characteristics into consideration at the
time of the medical examination interview before audio-psychological testing.
PMID- 29937849
TI - Cochlear implantation outcomes in children with common cavity deformity; a
retrospective study.
AB - Objective: A common cavity deformity (CCD) is a deformed inner ear in which the
cochlea and vestibule are confluent forming a common rudimentary cystic cavity
that results in profound hearing loss. There are few studies paying attention to
common cavity. Our group is engrossed in observing the improvement of auditory
and verbal abilities in children who have received cochlear implantation (CI),
and comparing these targets between children with common cavity and normal inner
ear structure. Material and methods: A retrospective study was conducted in 12
patients with profound hearing loss that were divided into a common cavity group
and a control group, six in each group matched in sex, age and time of
implantation, based on inner ear structure. Categories of Auditory Performance
(CAP) and speech intelligibility rating (SIR) scores and aided hearing thresholds
were collected and compared between the two groups. All patients wore CI for more
than 1 year at the Cochlear Center of Anhui Medical University from 2011 to 2015.
Results: Postoperative CAP and SIR scores were higher than before operation in
both groups (p < 0.05), although the scores were lower in the CCD group than in
the control group (p < 0.05). The aided threshold was also lower in the control
group than in the CCD group (p < 0.05). Conclusion: Even though audiological
improvement in children with CCD was not as good as in those without CCD, CI
provides benefits in auditory perception and communication skills in these
children.
PMID- 29937850
TI - Assessment of auditory and vestibular functions in vitiligo patients.
AB - Objectives: To evaluate audiological and vestibular functions via basic
audiological evaluation, otoacoustic emissions and videonystagmography (VNG) in
vitiligo patients. Material and methods: 30 vitiligo patients (8 acrofacial and
22 mixed types) as the study group and 30 normal healthy adults as the control
group were included in the study. All participants were submitted to basic
audiological evaluation, transient and distortion product otoacoustic emmisions
(TEOAEs and DPOAEs), vestibular assessment including history taking, office tests
and videonystagmography (VNG) and dermatological assessment to determine type,
percent of body surface area involvement and duration of vitiligo. Results: This
study showed statistically significant difference between control and study
groups in pure tone audiometry (PTA) and otoacoustic emissions results. Fifty
percent of vitiligo patients had peripheral vestibular disorders (10 vestibular
neuritis and 5 posterior canal benign paroxysmal positional vertigo. Conclusion:
The results in this study showed that 50% of vitiligo patients suffered from
peripheral vestibular disorders in addition to auditory affection. Vitiligo
patients require routine monitoring for auditory and vestibular functions for
early identification and monitoring of changes as the disease progress.
PMID- 29937851
TI - Apoptosis in inner ear sensory hair cells.
AB - Apoptosis, or controlled cell death, is a normal part of cellular lifespan. Cell
death of cochlear hair cells causes deafness; an apoptotic process that is not
well understood. Worldwide, 1.3 billion humans suffer some form of hearing loss,
while 360 million suffer debilitating hearing loss as a direct result of the
absence of these cochlear hair cells (Worldwide Hearing, 2014). Much is known
about apoptosis in other systems and in other cell types thanks to studies done
since the mid-20th century. Here we review current literature on apoptosis in
general, and causes of deafness and cochlear hair cells loss as a result of
apoptosis. The family of B-cell lymphoma (Bcl) proteins are among the most
studied and characterized. We will review current literature on the Bcl2 and Bcl6
protein interactions in relation to apoptosis and their possible roles in
vulnerability and survival of cochlear hair cells.
PMID- 29937852
TI - Treatment of benign paroxysmal positional vertigo. A clinical review.
AB - Benign paroxysmal positional vertigo (BPPV) is the most frequent episodic
vestibular disorder. It is due to otolith rests that are free into the canals or
attached to the cupulas. Well over 90% of patients can be successfully treated
with manoeuvres that move the particles back to the utriculus. Among the great
variety of procedures that have been described, the manoeuvres that are supported
by evidenced-based studies or extensive series are commented in this review. Some
topics regarding BPPV treatment, such as controlling the accuracy of the
procedures or the utility of post-manoeuvre restrictions are also discussed.
PMID- 29937854
TI - Temporal bone anatomy characteristics in superior semicircular canal dehiscence.
AB - Introduction: Superior semicircular canal dehiscence (SCD) remains difficult to
diagnose despite advances in high-resolution computed tomography (HRCT) imaging.
We hypothesize possible associations between gross temporal bone anatomy and sub
millimeter pathology of the semicircular canals, which may supplement imaging and
clinical suspicion. This pilot study investigates differences in gross temporal
bone anatomic parameters between temporal bones with and without SCD. Methods:
Records were reviewed for 18 patients referred to an otology clinic complaining
of dizziness with normal caloric stimulation results indicative of non-vestibular
findings. Eleven patients had normal temporal bone anatomy while seven had SCD.
Three-dimensional reconstruction of every patient's temporal bone anatomy was
created from patient-specific computational tomography images. Surface area (SA),
volume (V), and SA to V ratios (SA:V) were computed across temporal bone
anatomical parameters. Results: SCD temporal bones have significantly smaller V,
and larger temporal bone SA. Mean (+/-SD) V was 21,484 +/- 3,921 mm3 in temporal
bones without SCD and 16,343 +/- 34,471 mm3 for those with SCD. Their respective
SA were 13,733 +/- 1,603 mm2 and 18,073 +/- 3,002 mm2. Temporal bone airspaces
and lateral semicircular canals did not demonstrate significant differences where
SCD was and was not present. Plots of MVwarm response against computed SCD
temporal bone anatomic parameters (SA, V and SA:V) showed moderate to strong
correlations: temporal bone SA:V (r = 0.64), temporal bone airspace V (r = 0.60),
temporal bone airspace SA (r = 0.55), LSCC SA (r = 0.51), and LSCC-to-TM Distance
(r = 0.65). Conclusions: This analysis demonstrated that SCD is associated with
decreased temporal bone volume and density. The defect in SCD does not appear to
influence caloric responses.
PMID- 29937853
TI - "Wait and scan" management of patients with vestibular schwannoma and the
relevance of non-contrast MRI in the follow-up.
AB - Vestibular schwannoma (VS) is a slow-growing benign neoplasm. There has been an
evolution in the management of VS from active treatments (microsurgery and
stereotactic radiotherapy) to conservative management (wait and scan). Regular
MRI scanning is necessary to monitor tumor progression. Conservative management
causes significantly less complications and offers a higher quality of life
compared with active treatments. The mean growth rate of VS varies from 0.4 to
2.9 mm/year, and spontaneous shrinkage is observed in 3.8 percent of tumors
during observation. If significant growth occurs, active treatment is considered.
Significant growth is defined as an increase of at least 3 mm in the largest
extrameatal diameter in any plane between the first and last available scans. The
vestibulocochlear nerve is surrounded by cerebrospinal fluid, which provides
natural contrast for MRI; thus, gadolinium may not be needed to detect VS.
Specific sequences have high sensitivity, specificity, and accuracy for detection
of progression. Hypointense signal in the ipsilateral inner ear fluid might be a
useful sign to distinguish VS from meningioma. In this paper, we summarize the
current status of research on conservative management and non-contrast MRI for
the detection of VS.
PMID- 29937855
TI - Hearing evaluation after successful myringoplasty.
AB - Objectives: To assess postoperative hearing level, and factors that may have
influence hearing improvement after myringoplasty. Methods: Twenty six cases of
successful myringoplasty were included in this prospective study. Patient
parameters including age, gender, size and site of the perforation, mastoid
status, and etiology were evaluated. Hearing levels were assessed as the mean air
conduction (AC), and air-bone gap (ABG) at 500, 1000, and 2000 Hz, and their
relation with aforementioned parameters were analyzed. Results: The mean AC
hearing gain was 22.373 dB and mean ABG reduction was 20.733 dB. The maximum AC
hearing gain was 25.93 dB for subtotal perforation and 26.24 dB for big central
perforation, and the maximum ABG reduction was 25.63 dB for subtotal perforation
and 24.20 for big central perforation. Mean AC hearing gain was 23.01 dB, 22.72
dB, and 21.39 dB for 500, 1000, and 2000 Hz, respectively, and mean ABG reduction
was 21.52 dB, 20.79 dB, and 19.86 dB for 500, 1000, and 2000 Hz, respectively.
Patient age, gender, mastoid status and etiology did not seem to have any bearing
on postoperative hearing improvement. Conclusion: While patient parameters do not
seem to correlate with hearing improvement following myringoplasty, the size and
location of perforation appear to have an impact on postoperative hearing
outcomes. Most hearing improvement appears to occur at 500 Hz.
PMID- 29937856
TI - Does dyslipidemia worsen the hearing level in diabetics?
AB - Objective: To identify the effect of dyslipidemia on auditory function detected
by Pure Tone Audiometry. To check if dyslipidemia worsens the hearing level in
diabetics. Design: This was a comparative study where 120 subjects between the
age group of 20 and 50 years underwent pure tone audiometry, lipid profile and
blood sugars. Group 1 consisted of 30 subjects with type 2 diabetes and
dyslipidemia; Group 2 had 30 subjects with isolated diabetes; Group 3 had 30 with
isolated dyslipidemia and Group 4 included 30 normal subjects as control.
Results: Significant hearing loss was seen only in the group with isolated
diabetes (63%). The most common type of hearing loss was high frequency
sensorineural hearing loss. When comparison was made between the combinations of
different lipid profiles, no association was found to the level of hearing.
Conclusions: Diabetics are more prone to high frequency hearing loss. Altered
lipid profile has no role in causing hearing loss.
PMID- 29937857
TI - A case of auditory neuropathy revealed by OTOF gene mutation analysis in a junior
high school girl.
AB - Objective: Congenital auditory neuropathy (AN) affects hearing and speech
development. The degree of hearing difficulty in congenital AN varies as a
function of pathology at the inner ear hair cell (IHC) synapses or the auditory
nerve. We report a case of a Chinese girl with AN revealed by OTOF (otoferlin)
gene mutation analysis who had only a mild hearing loss. Patient: A 13-year-old
Chinese girl was diagnosed as having congenital AN on the basis of OTOF gene
mutation analysis. She manifest a mild sensorineural hearing loss with 50%
maximum monosyllable speech discrimination rate, normal DPOAEs (distortion
product otoacoustic emissions) beyond ambient noise levels, only SPs (summating
potentials) evoked during ECoG (electrocochleography) and absent ABRs (auditory
evoked brainstem responses) bilaterally to clicks presented at 100 dBnHL. She was
able to effectively communicate with others by speech reading owing to her mild
hearing loss. Moreover, bilateral hearing aids helped her to communicate.
Conclusions: Our patient was demonstrated to have a mutation on the OTOF gene.
Nevertheless, she was able to communicate using auditory visual speech reading in
spite of a mild auditory threshold elevation probably due to partial pathology at
the IHC synapses or in the auditory nerve.
PMID- 29937858
TI - An update on hearing impairment in patients with rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is a systemic, autoimmune disease that present with
intra-articular and extra-articular manifestations. Auditory system may be
involved during the course of RA disease due to numbers of pathologies. The link
between hearing impairment and RA has been discussed in the previous literature.
In this study we provide an update on the clinical aspect of hearing impairment
in RA. We suggest to test hearing in all newly diagnosed RA patients at diagnosis
as well as regularly during the course of disease.
PMID- 29937859
TI - Age predicts the absence of caloric-induced vertigo.
AB - Introduction: The absence of vertigo during the caloric test, despite a robust
response, has been suggested to represent a central vestibular system phenomenon.
The purpose of this investigation was to determine the prevalence of absent
caloric-induced vertigo perception in an unselected group of patients and to
assess possible predicting variables. Methods: Prospective investigation of 92
unselected patients who underwent caloric testing. Inclusion criteria were that
each patient generate a maximum slow phase velocity (maxSPV) >= 15 deg/sec and a
caloric asymmetry of <=10%. Following the caloric, patients were asked, "Did you
have any sensation of motion?" Results: Results showed 75% of patients reported
motion with a mean age of 56.51 years compared to a mean age of 66.55 in the 25%
of patients reporting an absence of motion. A logistic regression was performed
and the overall model was statistically significant accounting for 29% of the
variance in caloric perception. The significant predictor variables were patient
age and maxSPV of the caloric response. The effect size for both variables was
small with an odds ratio of .9 for maxSPV and 1.06 for age. Conclusions: The
current investigation showed that both age and maxSPV of the caloric response
were significant predictors of vertigo perception during the caloric exam.
However, the association between age and caloric perception is not conclusive.
Although there is evidence to suggest that these findings represent age-related
changes in the central processing of vestibular system stimulation, there are
additional unmeasured factors that influence the perception of caloric-induced
vertigo.
PMID- 29937860
TI - Assessment of auditory functions in chronic hepatitis C patients treated by
sofosbuvir.
AB - Objective: Evaluating the auditory function in patients with chronic hepatitis C
treated with sofosbuvir and ribavirin. Methods: This study involved 80 patients
with chronic hepatitis C who agreed to receive sofosbuvir and ribavirin. All
participants were subjected to baseline otological and audiological assessment
just before treatment. The audiological assessment included standard pure tone
audiometry, extended high-frequency audiometry, immitancemetry and otoacoustic
emissions (OAEs) (transient and distortion product). According to baseline
hearing threshold measurements, the study population was divided into 2 groups.
Group 1 included 42 patients with normal hearing sensitivity (250-8000 Hz), and
Group 2 included 38 patients with sensorineural hearing loss. After 24 weeks of
therapy, otological and audiological assessments were repeated and compared
between the two groups and before and after therapy. Results: Post-treatment
hearing threshold evaluation showed no significant difference from pretreatment
evaluation at all tested frequencies. There was no statistically significant
difference between pre and post-treatment otoacoustic emissions results.
Conclusion: Therapy with sofosbuvir and ribavirin in chronic hepatitis C has no
noticeable effects on cochlear functions.
PMID- 29937861
TI - A study on vestibular-evoked myogenic potentials via galvanic vestibular
stimulation in normal people.
AB - Objectives: The aim of our study is to examine vestibular-evoked myogenic
potentials (VEMPs) elicited by the galvanic vestibular stimulation in the
sternocleidomastoid muscle (SCM) in healthy subjects for clinical applications of
auditory neuropathy or vestibular neuropathy in the future. Methods: We enrolled
sixteen healthy subjects to record the average responses of SCM to galvanic
vestibular stimulation (GVS) [current 3 mA; duration 1 ms] by electromyography
(EMG). SPSS18.0 software was used to analyze the obtained data for mean and
standard deviation. Results: In all healthy subjects mastoid-forehead galvanic
vestibular stimulation produced a positive-negative biphasic EMG responses on SCM
ipsilateral to the cathodal electrode. The latency of p13 was 11.7 +/- 3.0 ms.
The latency of n23 was 17.8 +/- 3.4 ms. The amplitude of p13-n23 was 147.0 +/-
69.0 MUV. The interaural asymmetry ratio (AR) of p13, n23 latency and the
amplitude was respectively 0.12 +/- 0.09, 0.08 +/- 0.08 and 0.16 +/- 0.10.
Discussions: Galvanic vestibular stimulation could elicit biphasic EMG responses
from SCM via the vestibular nerve but not from the otolith organs. Galvanic
stimulation together with air conducted sound (ACS) or bone conducted vibration
(BCV) can elicit VEMPs and may enable the differentiation of retrolabyrinthine
lesions from labyrinthine lesions in vestibular system.
PMID- 29937862
TI - Does the use of recombinant TSH in preparation for I-131 scintigraphy scan affect
hearing function?
AB - Objective: The objective of this study was to examine the effect of
hypothyroidism on hearing function in patients surgically treated for
differentiated thyroid cancer and subsequently experienced hypothyroidism during
preparation for follow up I-131 scintigraphy scan by either recombinant human
thyroid stimulating hormone (rhTSH) treatment or thyroid hormone withdrawal
(THW). Methods: A total of 55 patients undergoing I-131 scintigraphy scan
following surgeries for differentiated thyroid cancer were included in the study,
including 25 patients prepared by administration of recombinant TSH (rhTSH Group)
and 30 patients by thyroid hormone withdrawal (THW Group). Results: Air
conduction thresholds at 1, 2 and 4 kHz for both ears were higher during
hypothyroid period than during euthyroid period for patients in the THW group (p
< 0.05) but not for patients in the rhTSH group. Conclusion: Sensorineural
hearing loss was detected, especially at low frequencies, in patients with DTC
after surgical treatment whose hormone replacement therapy was withdrawn but not
in those receiving rhTSH. It is therefore preferred to use rhTSH when preparing
for I-131 scintigraphy scan in patients at risk for hearing loss.
PMID- 29937863
TI - Application of high resolution computer tomography in external ear canal
cholesteatoma diagnosis.
AB - Objective: To evaluate High Resolution Computer Tomography (HRCT) in the
diagnosis of external ear canal cholesteatoma. Methods: In this retrospective
study, HRCTs of 27 patients with external ear canal cholesteatoma were reviewed.
The changes in the external ear canal, tympanic membrane (TM), scutum, tympanum
and mastoid were measured and categorized. Results: Fourteen patients showed no
or mild destruction in the external ear canal (stage I group). Eight patients had
obvious enlargement in the external ear canal (stage II group) but showed limited
destructions of the mastoid bone and no damage of the tympanums. Five patients
had serious destruction of the mastoid bone and damage of the tympanum (stage III
group). All patients in the stage III group showed a compression of manubriums
and TMs, with 3 having damages on ossicular chain. Bone destruction of the
vertical section of facial nerve canal was discovered in one case in the stage
III group. Conclusion: HRCT can provide detail information about the extent of
external ear canal cholesteatoma. Such information can be used to identify
special situations with serious complications and to differentiate external ear
canal cholesteatoma from middle ear cholesteatoma.
PMID- 29937864
TI - Impairment of extra-high frequency auditory thresholds in subjects with elevated
levels of fasting blood glucose.
AB - This study was performed to assess whether there is an association between
elevated Fasting Blood Glucose (FBG) and hearing impairment in Bangladeshi
population. A total of 142 subjects (72 with elevated FBG; 70 control) were
included in the study. The mean auditory thresholds of the control subjects at 1,
4, 8 and 12 kHz frequencies were 6.35 +/- 0.35, 10.07 +/- 0.91, 27.57 +/- 1.82,
51.28 +/- 3.01 dB SPL (decibel sound pressure level), respectively and that of
the subjects with elevated FBG were 8.33 +/- 0.66, 14.37 +/- 1.14, 38.96 +/-
2.23, and 71.11 +/- 2.96 dB, respectively. The auditory thresholds of the
subjects with elevated FBG were significantly (p < 0.05) higher than the control
subjects at all the above frequencies, although hearing impairment was most
evidently observed at an extra-high (12 kHz) frequency. Subjects with a long
duration of diabetes (>10 years) showed significantly (p < 0.05) higher level of
auditory thresholds at 8 and 12 kHz, but not at 1 and 4 kHz frequencies, compared
to subjects with shorter duration of diabetes (<=10 years). In addition, based on
the data of odds ratio, more acute impairment of hearing at the extra-high
frequency was observed in diabetic subjects of both older (>40 years) and younger
(<=40 years) age groups compared to the respective controls. The binary logistic
regression analysis showed a 5.79-fold increase in the odds of extra-high
frequency hearing impairment in diabetic subjects after adjustment for age,
gender and BMI. This study provides conclusive evidence that auditory threshold
at an extra-high frequency could be a sensitive marker for hearing impairment in
diabetic subjects.
PMID- 29937865
TI - The effect of interrupted anti-retroviral treatment on the reconstitution of
memory and naive T cells during tuberculosis treatment in HIV patients with
active pulmonary tuberculosis.
AB - Background: The reconstitution of cellular immune components contributes to
clinical outcome of HIV and Mycobacterium tuberculosis (MTB) infection.
Interruption of anti-retroviral therapy (ART) could lead to perturbations in
reconstitution of T cells in HIV/ tuberculosis (TB) patients. Objectives: To
ascertain the effect of interrupted ART on reconstitution of CD4+ and CD8+ T sub
sets in TB patients. Methods: Participants with HIV (CD4>350 cells/uL) and TB
were recruited under a larger phase 3 open label randomised controlled clinical
trial. The CD45RO and CD62L markers were measured on CD4+ and CD8+ cells by flow
cytometry. Samples were analysed at baseline, 3, 6, 12 months. Results: There was
a significant increase of naive CD8+ cells (p = 0.003) and a decrease in effector
CD8+ cells (p = 0.004) among participants in ART/TB treatment arm during the
first 6 months. Withdrawing ART led to naive CD8+ cells reduction (p=0.02) to
values close to baseline. An increase of naive CD8+ cells after 6 months of TB
treatment in TB alone treatment arm (p=0.01) was observed. A trend towards
increment of naive CD4+ sub sets in either treatment arms was observed.
Conclusion: Interrupting ART alters CD8+ but not CD4+ sub-sets in patients with
less advanced HIV infection and TB.
PMID- 29937866
TI - Prevalence and predictors of unknown HIV status among women delivering in Mulago
National Referral Hospital, Kampala, Uganda.
AB - Introduction: Knowledge of a person's HIV status during pregnancy is critical for
prevention of mother to child transmission of HIV. Objectives: To determine the
prevalence and factors associated with unknown HIV status among women delivering
in Mulago Hospital. Methods: This was a cross-sectional study of women that had
just delivered. The women's demographic characteristics, health seeking
behaviour, health system-related factors and knowledge on PMTCT were collected.
Fisher's exact test, Wilcoxon rank sum test and logistic regression were used to
test associations. Results: The prevalence of unknown HIV status was 2.6%
(10/382). Attending ANC at higher level facilities (OR =0.1 95% CI 0.0 - 0.4) and
having been counselled for HIV testing during ANC (OR=0.1, 95% CI 0.0 - 0.4) were
associated with likelihood of having a known HIV status. Out of the ten women
with unknown HIV status, 4/6 who attended ANC in public/government accredited
health facilities "opted out" of HIV testing due to personal reasons. Among the
four who attended ANC in private clinics, two were not offered HIV testing and
one "opted out". Conclusion: Most participants had a known HIV status at labour
(97%). Private clinics need to be supported to provide free quality HCT services
in ANC.
PMID- 29937867
TI - Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected
patients attending an urban HIV clinic in Uganda.
AB - Background: Co-infection with hepatitis B (HBV) and hepatitis D (HDV) is common
among human immunodeficiency virus (HIV) infected individuals in developing
countries and it aggressively accelerates progression of liver disease to
cirrhosis and other complications. There is scarcity of data on HDV in sub
Saharan Africa .We investigated the sero-prevalence and factors associated with
HDV antibody among HIV/HBV co-infected patients attending a large urban HIV
clinic in Uganda. Methods: We screened 189 HIV/HBV co-infected individuals for
anti-HDV immunoglobulin G (IgG) and performed logistic regression to determine
the associated factors. Socio-demographic, clinical data, immunological status,
and liver fibrosis (as determined by the Aspartate transaminase to platelet ratio
index and transient elastography) were included. Results: Participants were
predominately young and of sound immunologic status (median age 40 years, median
CD4 440 cells/ul). 98% were on ART regimens containing anti-HBV active
medications (95.2% were on TDF/3TC while 4.8% on 3TC containing regimen). Median
duration on ART was 36 months (IQR 22-72). Anti-HDV was detected in 6/198, 3.2%
(95% CI 1.14-6.92%), associated with male gender and a duration of more than 5
years since HIV diagnosis. Conclusions: The sero-prevalence of HDV antibodies
among the HIV/HBV co-infected patients is low in a Ugandan urban cohort.
PMID- 29937868
TI - The association between client type and condom use with steady and unsteady
partners among persons seeking HIV testing and counseling services in Kenya.
AB - Background: Approximately 70% of global HIV infections are located in sub-Saharan
Africa, and the prevalence of HIV infection in Kenya remains high. Objectives:
This study examined the association between client type (general population,
commercial sex worker [CSW], or truck driver) and consistent condom use with
steady and unsteady partners. Methods: Self-reported data included in the Kenyan
Ministry of Health 2010-2011 National HIV Testing and Counseling Registry were
used (n=11,567). Odds ratios (ORs) and 95% confidence intervals (CIs) were
obtained using logistic regression. Results: After adjustment, CSWs and truck
drivers had decreased odds of consistent condom use with steady partners compared
to the general population (OR=0.52; 95% CI: 0.41-0.67 and OR=0.29; 95% CI: 0.13
0.63; respectively). CSWs had 1.95 times the odds of consistent condom use (95%
CI: 1.58-2.42) and truck drivers had 0.64 times the odds of consistent condom use
with unsteady partners (95% CI: 0.45-0.91) compared to the general population.
Conclusion: Although CSWs consistently use condoms with their unsteady partners,
truck drivers do not consistently use condoms with any partners. Future HIV
prevention efforts should target CSWs and truck drivers to increase consistent
condom use with all partners. Such efforts may decrease the prevalence of HIV in
Kenya.
PMID- 29937869
TI - Angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility
to Kawasaki disease: a meta-analysis.
AB - Background: The angiotensin-converting enzyme (ACE) I/D polymorphism has been
reported to be associated with Kawasaki disease (KD), but studies to date present
conflicting results. Objectives: The aim of this study is to derive a more
precise estimation of the association between the ACE I/D polymorphism and KD
risk. Methods: PubMed, EMBASE, CNKI and Wangfang databases were retrievaled to
identify for relevant studies from inception to May 2017. Pooled odds ratios (OR)
with 95% confidence intervals (CI) were calculated using Stata 12.0 software.
Results: A total of 6 case-control studies comprising 634 patients and 458
controls were included in the meta-analysis, and we found a significant
association between the ACE I/D polymorphism and KD risk (D vs I:OR = 0.81, 95%CI
= 0.31-2.11;DD vs II: OR = 1.03, 95%CI = 0.42-2.54; DI vs II: OR = 1.44, 95%CI =
1.09-1.90; dominant model: OR = 1.43, 95%CI = 1.11-1.85; recessive model: OR =
1.21, 95%CI = 0.44-3.29 ). When stratified by sample size>200, this polymorphism
is associated with an increased the risk of KD. Conclusion: The I/D polymorphism
in the ACE gene may be associated with susceptibility to KD.
PMID- 29937870
TI - Prevalence of mecA gene among staphylococci from clinical samples of a tertiary
hospital in Benin City, Nigeria.
AB - Background: The staphylococci have increasingly been associated with infections
worldwide and anti-microbial resistance has made these versatile pathogens more
recalcitrant in the hospital setting. Objectives: This study sought to
investigate the occurrence and distribution of Staphylococcus species as well as
determine the prevalence of methicillin resistant Staphylococcus aureus (MRSA)
and methicillin resistant coagulase negative staphylococci (MRCoNS) among
clinical samples from University of Benin Teaching Hospital (UBTH) in Benin City.
Methods: Ninety one (91) clinical isolates comprising S. aureus and Coagulase
Negative staphylococci (CoNS) were recovered from routine clinical specimens and
anti-microbial susceptibility tests were carried out. Polymerase Chain Reaction
(PCR) was thereafter carried out on these isolates to detect mecA gene. Results:
Staphylococcus species had its highest prevalence from infected wounds of
patients (28.8%) while urine samples showed the least (5.4%). The highest level
of resistance was to ceftazidime (S. aureus - 68%, CoNS - 75.6%) while the least
resistance was observed for meropenem (S. aureus- 26%, CoNS- 46.3%). Using
phenotypic method (with 1ug oxacillin antibiotic disc), the distribution of MRSA
and MRCoNS was 44.0% and 46.3% respectively. PCR analysis showed that 38.0% of S.
aureus and 41.5% of the CoNS had mecA gene respectively; wound swabs showed the
highest prevalence with 30.5% of staphylococcal isolates being mecA gene
positive. There was also no significant association between the Staphylococcal
isolates and their isolation rate, isolation site and mecA gene distribution (p >
0.05). Conclusion: This study draws attention on the increase in the prevalence
of mecA gene (39.6%) and an increase in multidrug resistant staphylococci when
compared to previous studies in our country; it recommends laboratory guidance
and periodic review to stem the tide of resistance.
PMID- 29937871
TI - Evaluation and improvement of LAMP assays for detection of Escherichia coli
serogroups O26, O45, O103, O111, O121, O145, and O157.
AB - : Escherichia coli serogroups O26, O45, O103, O111, O121, O145, and O157 are the
causative agents of human diseases, and LAMP assays have been developed for
detection of the seven leading STEC serogroups. Objective: To evaluate existing
LAMP assays for detection of the seven STEC serogroups, if necessary, to improve
these assays and to promote their practical application. Methods: Pure DNA
extract from 23 strains reserved in our lab was used to evaluate the existing
LAMP assays. The existing LAMP assays were modified via adding 1% tetramethylene
sulfoxide and 5% dimethyl sulfoxide as well as optimizing reaction temperature.
Results: The detection limit of the modified LAMP assays was 0.1-1 pg per
reaction, equivalent to 25-250 cfu per reaction, the non-specific amplification
can completely be eliminated with optimal amplifying temperature, and the
modified LAMP assays can specifically and sensitivly amplify targeted O serogroup
specific gene (wzx or wzy) of any concerned Escherichia coli serogroup as
commercial kit Isothermal Master Mix did. Conclusion: In conclusion, the LAMP
assays were highly susceptible to non-specific amplification caused by primer
dimers, and these modified methods were free of non-specific amplification and
can rapidly and reliably detect the seven major Shiga toxin-producing E. coli
serogroups.
PMID- 29937872
TI - Seroprevalence of hepatitis E in swine abattoir workers.
AB - Background: Hepatitis E (HE) caused by Hepatitis E virus (HEV) is an emerging
global public health threat. It has been identified as potentially zoonotic and
swine act as main reservoirs. Objectives: The objective of this study was to
determine the seroprevalence and risk factors associated with HEV in swine
abattoir workers. Methods: This was a cross-sectional study where 45 workers were
sampled (N=50), serum collected and tested for presence of anti HEV IgM using
ELISA. Results: A seroprevalence of 13.3% was obtained with the highest 50% among
slaughterers and the lowest amongst sanitary cleaner, cloth cleaners and
inspector. Those in direct contact with live pigs, their carcasses and tissues
were at a higher risk compared to those in indirect contact. Seroprevalence was
seen to increase with age, with the highest rate among those above 24 years.
Conclusion: There is silent HE virus infection in abattoir workers at Wambizi as
reflected by presence anti HEV IgM in 13% of the tested serum. However, no single
case of HE has ever been reported in swine abattoir workers or general population
in Kampala city. This silent maintenance of HEV infection amongst swine abattoir
workers is an occupational risk that could challenge public health systems.
PMID- 29937873
TI - Plasma ACTH concentration and pituitary gland histo-pathology in rats infected
with Trypanosoma brucei brucei.
AB - Background: Human African trypanosomiasis is one of the neglected and re-emerging
infectious diseases in Africa with over 60 million people being at risk of
contracting the disease. Objective: To investigate the effects of Trypanosoma
brucei brucei infection on secretion of adrenocorticotropic hormone (ACTH) and
histology of the pituitary gland and paraventricular nucleus in rats. Methods:
Rats were randomly divided into two groups, control and experimental.
Experimental rats were injected intraperitonially with 0.2ml of blood containing
1.0 * 104 live T.b.brucei parasites. Tail blood samples were collected weekly for
the determination of plasma concentration of ACTH. The pituitary gland and
coronal section of brain were processed histologically and observed
microscopically. Results: There was a significant difference (p = 0.0190) in
plasma ACTH concentration between the control and experimental rats. Histological
alterations were observed in both the pituitary and paraventricular nucleus of
experimental rats. Conclusion: T.b.brucei infection causes histological changes
in both the paraventricular nucleus and pituitary gland in rats. These
histological changes could account for the decrease in corticotropin releasing
hormone (CRH) and ACTH production in the infected rats.
PMID- 29937875
TI - Mammographic classification of breast lesions amongst women in Enugu, South East
Nigeria.
AB - Objectives: The study was to classify lesions identified on mammograms using
Breast Imaging Reporting and Data System (BIRADS) grading method. This was in
view of ascertaining the rate of occurrence of breast malignancy of the studied
population. Methods: A retrospective cohort study of 416 mammographic reports of
women was undertaken. The reports were written by consultant radiologists of 10
years' experience and above. The reports were evaluated and characterised using
Breast Imaging Reporting and Data system (BIRADS). Demographic data of patients
were sourced from the request cards. The data was entered into a proforma and
analysed using SPSS version 17. All request cards with incomplete data were
excluded from the study. Results: Using the BI-RADS Classification, the
mammographic reports shows that 29.57% of the lesions were benign, and 4.57% were
suspicious and biopsy recommended, while 3.60% were highly suggestive of
malignancy. The right breast was predominantly affected with 42.7% of the
patients (P<0.05). Conclusion: Classification of breast lesion using BI-RADS
grading system is a veritable tool in the diagnosis of the breast lesion. The
present study shows that 3.6% of the population has a high index of malignancy.
PMID- 29937874
TI - Breast cancer metastasis to thyroid: a retrospective analysis.
AB - Background: Breast cancers metastasizing to thyroid gland are relatively uncommon
in clinical practice. Objective: Retrospective analysis of data from breast
cancer patients with thyroid metastasis (TM). Methods: The US suspected, fine
needle aspiration cytology (FNAC) confirmed TM in breast cancer patients, treated
between 2005 and 2015 at our hospital, was retrospectively analyzed. The data
were re-evaluated by the pathologist and radiologist who were blinded to the
patients' data. Results: FNAC and immunohistochemistry confirmed the
ultrasonography (US) suspected TM in eight breast cancer patients. Clinically
both unilateral and bilateral TM was seen, which were symptomless and
metachronously (6-121 months) metastasized. Six of eight cases exhibited
recurrence/distant metastasis and were treated with chemotherapy/thyroidectomy of
which two cases passed away. The remaining two patients had no
recurrences/distant metastases and were treated with partial/total thyroidectomy.
Post-chemotherapy US showed more homogenous thyroid parenchyma with gathering of
calcification that reduced in size, revealing the sensitiveness of TM to
chemotherapy. Conclusion: US was useful in screening TM in breast cancer
patients. Both partial and total thyroidectomy was effective in disease free
survival of isolated TM cases, with controlled primary condition. TM responded
well to chemotherapy in most of the recurrent breast cancer cases with or without
distant metastasis.
PMID- 29937876
TI - Gastrointestinal malignancies at five regional referral hospitals in Uganda.
AB - Background: There is a paucity of published data regarding the trend and
distribution of gastrointestinal malignancies in Uganda. Objectives: To study the
trend and distribution of gastrointestinal malignancies over a 10 year period at
five regional referral hospitals in Uganda. Methods: Patient's charts with
histologically confirmed diagnoses of gastrointestinal malignancies for the
period 2002-2011 were identified. Case information, which included age at
diagnosis, sex, and year of diagnosis, primary anatomic site of the tumour and
hospitals attended, was retrospectively abstracted. Patient's clinical and
demographic features were compared. Results: Oesophageal cancer was the most
common (28.8%) followed by liver (25.8%), stomach (18.4%) and colorectal (14.3%).
The mean age at diagnosis for all the cancers was not significantly different in
both sexes 54.1, (SD16.1) versus 53.6, (SD 14.7). The highest mean annual number
of cases of oesophageal and stomach cancers was 21.8, (SD 15.5) and 16.6, (SD
13.0) respectively from Mbarara Hospital; Lacor had the highest mean annual
number of liver cancer cases (21, SD 17.7) followed by Mbale (11.4, SD 8.3). The
mean annual number of colorectal cancers was highest in Mbale Hospital (10.3, SD
8.1) followed by Lacor (4.9, SD 3.9). The distribution of oesophageal, liver,
stomach and colorectal cancers diagnosed per year across the five referral
hospitals was different, P<0.001. Conclusion: Oesophageal, liver, stomach and
colorectal cancer remain the most common gastrointestinal malignancies and their
rate is increasing in Uganda. There is a need for awareness, endoscopic and
radiological assessment of symptomatic individuals and a need for screening of
high index patients.
PMID- 29937877
TI - Analysis of SNPs of MC4R, GNB3 and FTO gene polymorphism in obese Saudi subjects.
AB - Background: The goal of this study was to analyze the association between the FTO
rs17817449 (G>T), G protein beta3 subunit (GNB3) C825T and Melanocortin 4
receptor (MC4R) A822G single nucleotide polymorphism (SNP) with obesity in Saudi
subjects. Methods: The subjects were divided into 2 groups according to BMI:
Obese (BMI> 29.9) and non- obese control (BMI<24.9). Genotyping of the target
genes were determined by polymerase chain reaction (PCR) followed by restriction
fragment length polymorphism analysis (RFLP). Results: We demonstrated the
association of the FTO genotype TT with increased weight, BMI and leptin levels
in both males and females. However, there was no association of genotype TT with
fasting blood glucose, triglycerides and cholesterol levels. Regarding GNB3
rs5443 polymorphism, the likelihood of obesity was linked to the TT genotype
which was also associated with increased leptin levels. On the other hand, the
SNP of MC4R A822G did not exhibit any significant association with obesity among
studied subjects and showed only the presence of homozygous AA genotype.
Conclusion: The polymorphism of FTO gene rs17817449 and GNB3 gene rs5443 (C825T)
may be a genetic determinant of obesity in Saudi population whereas impact of
MC4R Asn274Ser change could not be detected.
PMID- 29937878
TI - Cardiovascular risk factors in adult general out-patient clinics in Nigeria: a
country analysis of the Africa and Middle East Cardiovascular Epidemiological
(ACE) study.
AB - Background: With globalization and rapid urbanization, demographic and
epidemiologic transitions have become important determinants for the emergence of
cardiovascular disease (CVD). Objective: To estimate the prevalence of CVD risk
factors in adult out-patients attending general practice and non-specialist
clinics in urban and rural Nigeria. Methods: As part of the Africa and Middle
East Cardiovascular Epidemiological (ACE) study, a cross-sectional epidemiologic
study was undertaken for the presence of hypertension, diabetes mellitus,
dyslipidemia, obesity, smoking and abdominal obesity in Nigeria. Results: In
total, 303 subjects from 8 out-patient general practice clinics were studied, 184
(60.7%) were female and 119 (39.3%) were male. Mean age was 42.7+/-13.1 years;
51.8% were aged <45 years; 4% >=65 years. Over 90% of subjects had >=1 of 6
selected modifiable cardiovascular risk factors: 138 (45.6%) had 1-2; 65 (21.5%)
had 3; 60 (19.8%) had 4; and 11 (3.6%) had 5 concurrent risk factors. Screening
identified 206 subjects (68.0%) with dyslipidemia who did not have a prior
diagnosis. Conclusion: Cardiovascular risk factors are highly prevalent in
Nigerian subjects attending out-patient clinics. Moreover, many subjects were
undiagnosed and therefore unaware of their cardiovascular risk status.
Opportunistic screening alongside intensive national, multisectoral education or
risk factor education is needed, should be scaled up nationwide and rolled out in
both urban and rural communities in Nigeria.
PMID- 29937879
TI - Oral dysbacteriosis in type 2 diabetes and its role in the progression to
cardiovascular disease.
AB - Background: Salivary changes and proliferation of specific bacterial communities
are known to result in oral disease which may adversely impact on systemic
conditions like diabetes and cardiovascular diseases. Objectives: This study
reports on the changes in oral ecology of healthy and diseased adults and the
possible role in disease causation. Methods: The study comprised 150 participants
divided into control (healthy), diabetic and cardiac groups. After dental
examination for (Decayed Missing Filled Teeth (DMFT) and Oral Rating Index (ORI),
stimulated saliva was sampled to determine flow rate and buffering capacity.
Salivary microbial load of Streptococcus mutans and Lactobacilli were
subsequently quantified. Results: DMFT, ORI, buffering capacity and flow rate
were inferior for both diabetic and cardiac patients, who had higher bacterial
counts (p<0.05). Long standing diabetics harboured a higher load of Streptococcus
mutans. The microbial load of Streptococcus mutans in cardiac patients was double
that of diabetics. Conclusion: Disruption in the salivary environment and changes
in microbial ecology with increased load of cariogenic bacteria were found in
diabetic and cardiac patients. This study brings forward new evidence of a
markedly higher load of Streptococcus mutans in cardiac patients which may
underlie the progression of diabetes to cardiovascular disease in this
population.
PMID- 29937880
TI - QTc prolongation in Black diabetic subjects with cardiac autonomic neuropathy.
AB - Background: Prolonged corrected QT (QTc) has been identified as a risk factor for
malignant arrhythmias and sudden cardiac death. Caucasian studies have shown a
definite relationship between QTc prolongation and Cardiac Autonomic Neuropathy
(CAN) in diabetic subjects. Objective: To determine the prevalence of prolonged
QTc in Black diabetic individuals with CAN and to ascertain how prolonged QTc
correlated with the severity of CAN among these patients. Methods: A total of 176
adult diabetic subjects were studied, 87 males and 89 females. There was a
control group of non-diabetic individuals. Cardiac autonomic function was
assessed using five cardiovascular autonomic function tests. CAN was diagnosed if
2 or more of these tests were abnormal. Severity of CAN was determined according
to the number of abnormal tests. QTc > 0.440 was regarded as prolonged. Results:
Fifty-one out of the 176 diabetic subjects (29%) had CAN. The prevalence of
prolonged QTc in diabetic subjects with CAN was 12%. QTc was prolonged in 1.6%
and 0.6% of diabetic individuals without CAN and controls respectively. Although
QTc correlated strongly with cardiac autonomic function neuropathy, there was no
definite relationship between QTc prolongation and severity of CAN. Conclusion:
This study in a Black population is in agreement with the well-known relationship
between QTc prolongation and CAN reported in Caucasian studies. In view of the
wide variability of QTc in this study population, it is suggested that relative
QTc increase may be a better indicator of CAN than a definite QTc prolongation of
greater than 0.440.
PMID- 29937881
TI - Role of offending out-door aero-allergen and CD14 C(-159)T polymorphism in
development and severity of asthma in a Kolkata patient population.
AB - Objective: Present study involved identification of offending out-door aero
allergens and associated genetic pathway in nasso-bronchial asthma among Kolkata
population. Methods: Skin-prick test was done among 950 asthmatic patients
against 11 common aero-allergens and total serum IgE concentration was measured.
PCR-RFLP was done in patients and non-asthmatic control (n=220 in each) to
characterize functional polymorphism, C(-159)T, of CD14, a positional candidate
gene for allergy. Association of genetic polymorphisms was made with clinico
pathological conditions. Results: We identified Cocos nucifera as the most common
aero-allergen sensitizer among atopic patients in Kolkata. Patients with
childhood-onset asthma were significantly more sensitive towards aero-allergens
and had significantly higher serum IgE level than those of adult-onset (p<
0.0001). No significant difference was found in distribution of SNP genotypes of
CD14 among case and control (p=0.178). However among patients, frequency of C
allele is significantly higher in childhood-onset group than that of adult-onset
and concordantly in former CC genotype was associated with significant higher
level of serum IgE than CT and TT. Conclusion: In Kolkata, pollen is a common out
door aero-allergen and Cocos nucifera is predominant among pollens. Childhood
onset and adult-onset of asthma showed significant difference in allergen
sensitivity as well as genetic background with respect to CD14 polymorphism.
PMID- 29937882
TI - The prevalence of and factors associated with tobacco smoking behavior among long
distance drivers in Lagos, Nigeria.
AB - Background: Factors associated with tobacco smoking are useful in designing
tobacco control programs. Objectives: To estimate the prevalence of and factors
associated with tobacco smoking among long-distance drivers. Methods: A cross
sectional study. Stratified cluster sampling approach was used to select drivers
based on if they received annual health screening (AHS) or not (non-AHS). We used
a structured questionnaire to obtain information and weighted the resulting
observations to derive population based estimates. Association between tobacco
smoking and socio-demographic factors was explored in multivariate models.
Results: A total of 414 male drivers, with a mean age of 43.6 (standard error
0.6) years were studied. Population weighted prevalence of current smoking was
18.9% (95% CI: 14.3-23.4) all drivers, 6.5% (95% CI: 2.6-10.4) of AHS drivers and
19.5 (95% CI: 14.7-24.2) of non-AHS drivers (p<0.001). In multivariate models,
having close friends that smoked (OR= 6.36, 95% CI= 2.49 - 16.20) cargo driving
(OR= 2.58, 95% CI= 1.29 - 5.15) and lower education levels (OR for post-secondary
education vs. Primary education or less= 0.17, 95% CI= 0.04 - 0.81) were
associated with current smoking. Conclusion: Prevalence of tobacco smoking is
higher among non-AHS compared to AHS drivers. Having close friends that smoked,
cargo driving, and lower education levels were associated with current smoking.
PMID- 29937884
TI - Common childhood kidney diseases in Uganda and their prevention.
PMID- 29937883
TI - Abnormalities of the external genitalia and groins among primary school boys in
Bida, Nigeria.
AB - Background: Abnormalities of the male external genitalia and groin, a set of
lesions which may be congenital or acquired, are rather obscured to many kids and
their parents and Nigerian health care system has no formal program to detect
them. Objectives: To identify and determine the prevalence of abnormalities of
external genitalia and groin among primary school boys in Bida, Nigeria. Methods:
This was a cross-sectional study of primary school male pupils in Bida. A
detailed clinical examination of the external genitalia and groin was performed
on them. Results: Abnormalities were detected in 240 (36.20%) of the 663 boys,
with 35 (5.28%) having more than one abnormality. The three most prevalent
abnormalities were penile chordee (37, 5.58%), excessive removal of penile skin
(37, 5.58%) and retractile testis (34, 5.13%). The prevalence of complications of
circumcision was 15.40% and included excessive residual foreskin, excessive
removal of skin, skin bridges and meatal stenosis. Undescended testes were seen
in 6 (0.90%) boys, with median age of 9 years and 2 were bilateral. Also,
micropenis was detected in 27 (4.07%) of the pupils. Conclusion: Inguino
penoscrotal abnormalities are common in our community (36.20%). Screening of pre
school and school children to detect them should be introduced into the school
health programs in Nigeria.
PMID- 29937885
TI - Idiopathic nephrotic syndrome in South African children.
AB - Background: Different histo-pathological types and treatment response patterns of
Idiopathic nephrotic syndrome (INS) have been associated with differences in
ethnicity and geographical location. Objective: To provide an update on the
steroid response and renal histo-pathological pattern in children treated for
INS. Method: Medical records of children with INS treated at the Charlotte Maxeke
Johannesburg Academic Hospital were reviewed. Results: Mean age was 5.3 years +/-
2.8. The majority (68.1%) of the 163 children were of the black racial group. The
highest rate of INS was seen in the 2-6 year age group (71.2%). The black racial
group had the highest rate (42/111; 37.8%) of focal segmental glomerulosclerosis
(FSGS), and the white race had the highest rate (9/14; 64.3%) of minimal change
disease (MCD). Ninety four (57.7%) patients were steroid sensitive (SSNS) while
69 patients (42.3%) were steroid resistant (SRNS). Minimal change disease was the
most common histo-pathological type seen in SSNS (60%), while FSGS was the most
common observed in patients who had SRNS (65.2%). Conclusion: There appears to be
a higher rate of FSGS in all the racial groups, and also a higher rate of MCD in
the black race group, when compared to previous reports.
PMID- 29937887
TI - The reality of every day communication for a deaf child using sign language in a
developing country.
AB - Background: Research that focuses on the communication between deaf children and
their hearing families is scarce despite the majority of deaf children being born
into hearing families where a common communication mode needs to be forged.
Objective: The aim of the study was to explore, describe and compare the nature
of communication across typical daily contexts of a deaf child who uses South
African Sign Language (SASL) and who is born into a hearing family with no prior
experience of SASL. Methods: A case study design which included quantitative and
qualitative components was used to observe a nine year old grade one child with
profound hearing loss. Spontaneous communication was observed with 13
communication partners in the home context and these included the mother, a
sibling and peers. Two educators and 11 peers were observed in the educational
context. Surveillance cameras were used to obtain 27 hours of video-recording in
the home and 19 hours at the school. Interviews were conducted with the mother,
siblings, educators, and the deaf child. Results: It was observed that
communication using SASL, albeit minimal, home signs, natural gestures and oral
communication were used extensively. Due to a mismatch in the communication mode
in the home context communication interactions were fewer and predominantly oral,
impoverished and with frequent breakdowns whereas the communication interactions
in the school were characterized by SASL, was meaningful and had fewer
communication breakdowns. Conclusion: Communication for deaf children within the
home is problematic as communication partners are not fluent in SASL.
PMID- 29937886
TI - Long term effect of a school based intervention to prevent chronic diseases in
Tunisia, 2009-2015.
AB - Background & Objectives: We aimed to evaluate the long term effect of school
based intervention to prevent non- communicable disease risk factors. Methods: It
was a quasi experimental study conducted during the period of 2009-2015. We
involved school children aged from 11 to 16 years old. For the assessment of the
program's effectiveness, subjects in both groups were examined at baseline, at
the end of the 3-year intervention period and at the follow-up, one year after
program's cessation. Results: In the intervention group, the prevalence of school
children who reported to be eating 5 fruits and vegetable sdaily increased
significantly from 30.0% at pre-assessment to 33.2% at post-assessment, one year
after (p=0.02, p=0.41 respectively). For the control group, this prevalence had
significantly decreased from 40.2% at baseline to 35.0% at post-intervention, at
the follow up, this proportion increased to 44.5%(p=0.001, p<10-3 respectively).
Concerning smoking habits, we observed a decreasing trend in the intervention
group from 5.7% at pre-assessment, to 4.8% at post-assessment and to 3.4% at the
follow-up (p=0.19 and p=0.25 respectively). There was also a significant decrease
in school children who did recommended physical activity in the same group.
Conclusion: The present work showed that interventions promoting healthy
lifestyles should be maintained. Developing countries should be encouraged and
supported to design, conduct, and evaluate robust preventive interventions.
PMID- 29937888
TI - Characteristics of astigmatism in Black South African high school children.
AB - Background: Astigmatism impairs vision at various distances and causes symptoms
of asthenopia which negatively impacts reading efficiency. Objective: The aim of
conducting this study was to determine the prevalence and distribution of
astigmatism and its relationship to gender, age, school grade levels and
spherical ametropia. Methods: Using a multi-stage random cluster sampling, 1589
children who included 635 (40%), males, and 954 (60%), females were selected from
13 out of a sample frame of 60 schools. Their ages ranged between 13 and 18 years
with a mean of 15.81+/-1.56 years. The parameters evaluated included visual
acuity using the LogMAR chart and refractive errors measured using an
autorefractor and then refined subjectively. Axis of astigmatism was presented in
the vector method where positive values of J0 indicated with-the-rule, negative
values described against-the-rule and J45 represented oblique astigmatism.
Results: The mean cylinder power was -0.09 +/- 0.27 and mainly with-the-rule, J0
= 0.01 +/- 0.11. The overall prevalence of clinically significant astigmatism (<=
- 0.75 cylinder) in the sample was 3.1% [(95% Confidence interval = 2.1-4.1%)].
Cylinder of at least - 0.25 power was considered to classify astigmatism types.
Thus, the estimated distributions of types of astigmatism were: axis- 11.5%,
sphero-astigmatism 10.1% and magnitude-astigmatism 11.2% while 67.2% had no
cylinder of any magnitude. Conclusion: The prevalence of astigmatism is
relatively low in this population studied. Older children and those in high
school grade levels were more likely to have with-the-rule or against-the-rule
astigmatism. The prevalence of astigmatism were comparable within but not across
regions.
PMID- 29937889
TI - Suicidal ideation and associated factors among school going adolescents in
Swaziland.
AB - Background and objective: Suicide among children has been a major issue and the
statistics are considerably alarming. However, no studies have been conducted in
Swaziland on suicidal ideation which is a starting point for committing suicide.
The objective of the study was to determine the prevalence of suicidal ideation
and its correlates. Methods: A secondary analysis of data was conducted using
data collected in a Swaziland 2013 Global School-based Student Health Survey
(GSHS). The survey assessed among other factors, mental health of the students
using a self-administered questionnaire. We considered factors that have been
reported to be associated with suicidal ideation in the literature. Unadjusted
odds ratios (OR) and adjusted odds ratios (AOR) together with their 95 confidence
intervals (CI) are reported. Results: The overall proportions of students who
considered suicide were 18.3% of 1866 females and 15.6% of 1672 males. In
bivariate models the risk factors for suicidal ideation were feeling lonely,
anxiety, using drugs and smoking marijuana. In multivariate model to include age,
gender, food security, close friends, truancy, bullied, attacked, physical fight,
drugs, marijuana, parental understanding anxiety and loneliness, all the
considered factors were significantly associated with suicide except close
friends. Conclusion: The rate of suicidal ideation was high among adolescents in
Swaziland and intervention considering violence, social support from friends and
parents, and drug abuse should be designed to prevent suicidal thoughts.
PMID- 29937890
TI - Intestinal candidiasis and antibiotic usage in children: case study of Nsukka,
South Eastern Nigeria.
AB - Background: Overgrowth of candida results from factors that disrupt the
intestinal microbial balance, such as the use of antibiotics. Unregulated
antibiotic use and rampant practice of self-medication in Nigeria, is a cause for
concern. Methods: A total of 314 stool specimens were collected from children <1
to 12 years of age in Nsukka, South Eastern Nigeria and screened for candida
species using standard methods. Questionnaires were used to collect relevant
information on the participants. Results: Out of the 314 participants, 31.2% had
candidiasis, indicated by growth of >=105 CFU/ml. Four different species of
candida were identified. Candida albicans had the highest prevalence (59.0%),
while Candida krusei had the least prevalence (6.0%). Of the 314 participants,
46.5% had diarrhoea, out of which 58.9% had intestinal candidiasis while only
14.3% of the non-diarrhoeic children had candidiasis. Of 208 participants who had
taken antibiotics within three weeks of the study, 42.3% had candidiasis compared
to 20.8% of those with no recent history of antibiotic use. Conclusion: The
results of this study showed a high prevalence of intestinal candidiasis among
children in Nsukka. Strong associations were observed between the presence of
intestinal candidiasis and diarrhoea, age and use of antibiotics (p<0.001).
PMID- 29937891
TI - Assessing regional variations in the effect of the removal of user fees on
facility-based deliveries in rural Zambia.
AB - Background: Maternal health remains a concern in sub-Saharan Africa, where
maternal mortality averages 680 per 100,000 live births and almost 50% of the
approximately 350,000 annual maternal deaths occur. Improving access to skilled
birth assistance is paramount to reducing this average, and user fee reductions
could help. Objective: The aim of this research was to analyse the effect of user
fee removal in rural areas of Zambia on the use of health facilities for
childbirth. The analysis incorporates supply-side factors, including quantitative
measures of service quality in the assessment. Method: The analysis uses
quarterly longitudinal data covering 2003 (q1)-2008 (q4) and controls for
unobserved heterogeneity, spatial dependence and quantitative supply-side factors
within an Interrupted Time Series design. Results: User fee removal was found to
initially increase aggregate facility-based deliveries. Drug availability, the
presence of traditional birth attendants, social factors and cultural factors
also influenced facility-based deliveries at the national level. Conclusion:
Although user fees matter, to a degree, service quality is a relatively more
important contributor to the promotion of facility-based deliveries. Thus, in the
short-term, strengthening and improving community-based interventions could lead
to further increases in facility-based deliveries.
PMID- 29937893
TI - World Medical Association Declaration of Geneva.
PMID- 29937892
TI - The market dynamics of selective serotonin re-uptake inhibitors: a private sector
study in South Africa.
AB - Objective: The objective of this study was to analyse the market share of generic
vs originator selective serotonin re-uptake inhibitors (SSRIs), and also compare
market share of different SSRIs in the private health care sector in South
Africa, over a period of 4 years. Methodology: This was a retrospective,
descriptive study that measured generic market volume as a percentage of the
total private SSRI market volume. Retail private sector sales data for six SSRIs
available in the private sector in South Africa was evaluated. Sales data were
obtained from various stages in the pharmaceutical supply chain, June 2009 - May
2013. Results: Generics constituted 86% and originators 14% of the private sector
market volume of SSRIs. The share of the market volume of generic medicines
increased by 29.93% over this 4-year period, while an overall increase of 27.86%
in the ratio of generics to originators was observed. Conclusion: In line with
policies, generic SSRIs hold a larger volume of the market in the private sector
in South Africa.
PMID- 29937894
TI - Changes in erythrocyte ATPase activity under different pathological conditions.
AB - Background: Studies have shown that Na+-K+ ATPase activity was altered in
disrupted red blood cell membranes and this enzyme is believed to be the site of
active transport of Na+ and K+ in intact red blood cells. The enzyme is often
referred to as Na+-K+ pump because it pumps Na+ out and K+ into the cell against
gradients with the concomitant hydrolysis of intracellular ATP. Objective: The
aim of this study was to find out the possibility of using Na+-K+-ATPase activity
as a biomarker for the diagnosis of individuals with different physiological
conditions. Materials and methods: The activity of Na+-K+ ATPase was determined
in blood samples collected from different pathological and physiological
conditions such as pregnancy, smoking, diabetes and renal dysfunction compared
with healthy subjects matched for age and sex. Results: The Na+-K+ ATPase
activity in pregnancy (0.094 +/- 0.0051 uM Pi/min. mg protein), smoking (0.064 +/
0.0011 uM), diabetes (0.047 uM 0.002 uM) and kidney disease (0.069 +/- 0.0014
uM) was higher compared to the measurements in healthy individuals (0.0081 +/-
0.0031 uM). Conclusion: Na+-K+ATPase specific activity is a biomarker for the
diagnosis of individuals with different physiological diseases.
PMID- 29937895
TI - Neurocalcin-delta: a potential memory-related factor in hippocampus of obese rats
induced by high-fat diet.
AB - Introduction: Aberrant protein expression within the hippocampus has recently
been implicated in the pathogenesis of obesity-induced memory impairment.
Objectives: The objective of the current study was to search for specific memory
related factors in the hippocampus in obese rats. Methods: Sprague-Dawley (SD)
rats were fed either a high-fat (HF) diet or normal-fat (NF) diet for 10 weeks to
obtain the control (CON), diet-induced obese rats (DIO) and diet-resistant (DR)
rats. D-galactose was injected subcutaneously for 10 weeks to establish model
(MOD) rats with learning and memory impairment. After the hippocampus of the rats
sampling, the proteome analysis was conducted using two-dimensional get
electrophoresis (2-DE) combined with peptide mass fingerprinting (PMF). Results:
We found 15 differential proteins that expressed in the hippocampus in rats
induced by HF diet from the 2-DE map. In addition, Neurocalcin-delta (NCALD) was
nearly down-regulated in the DR rats compared with CON rats and MOD rats, which
was further confirmed by Western blot, real-time PCR and ELISA results.
Conclusion: Our data demonstrates that the differential memory-related proteins
were a reflection of the HF diet, but not potential factors in obesity proneness
or obesity resistance. Furthermore, NCALD is proved to be a potential hippocampus
memory related factor related to obesity.
PMID- 29937896
TI - Reproducibility of corneal, macular and retinal nerve fiber layer thickness
measurements using the iVue-100 optical coherence tomography.
AB - Purpose: To determine the intra-session and inter-session reproducibility of
corneal, macular and retinal nerve fiber layer thickness (RNFL) measurements with
the iVue-100 optical coherence tomography in normal eyes. Methods: These
parameters were measured in the right eyes of 50 healthy participants with normal
vision. Six scans each for corneal thickness, macular and optic nerve head were
taken on one day (intra-session), followed by similar repeated measures on five
separate days (inter-session). Reproducibility was computed using intra-class
correlation coefficient (ICC), coefficient of variation (COV), and test-retest
variability (TRV). Results: For intra-session reproducibility, the ICC, COV and
TRV values for mean corneal thickness were 0.924, 2.82%, and 3.06 um
respectively. For the mean macular thickness, they were 0.978, 4.64% and 4.51 um
respectively, while for mean RNFL thickness they were 0.946, 3.19%, and 5.66 um
respectively. Inter-session values for mean corneal thickness were 0.926, 2.65%
and 3.48 um, and 0.916, 2.24% and 2.03 um for mean macular thickness. For mean
RNFL thickness, they were 0.962, 2.21%, and 4.72 um respectively. Conclusion:
There was good reproducibility of all measured parameters. However, mean RNFL
thickness measurements were the most reproducible, suggesting that this may be
the best parameter to use to determine measured changes over time.
PMID- 29937897
TI - Sub-clinical middle ear malfunctions in elderly patients; prevalence, pattern and
predictors.
AB - Background: Little is known about functioning of the middle ear with advancing
age. Objectives: To estimate the prevalence and describe tympanometric patterns
of sub-clinical middle ear malfunctions,( S-MEM) in elderly patients. It also
assessed clinical factors that could predict S-MEM. Methods: Cross-sectional,
analytical study of patients aged >= 60 years in a tertiary hospital in Nigeria
between 2011-2014. Pure tone audiometry (PTA), tympanometry and acoustic reflexes
were recorded. S-MEM was based on audiometric and tympanometric evident
abnormalities. Descriptive, univariate and multivariate analyses performed to
detect independent clinical predictors of S-MEM at p-value of <0.05. Results: 121
patients , M: F of 1.1:1. Mean age was 70.1 +/- 6.2 years, 77.7% were married.
Prevalence of S-MEM was 21.5%. Abnormal tympanometric tracings were type
AS>C>B>AD. The parameters that were statistically-significant on univariate
analyses were subjected to logistic regression analysis which confirmed previous
head injury, diabetes, osteoarthritis of knee joint, and absent acoustic reflex
as clinical predictors for S-MEM. Conclusion: 21.5% of elderly Africans had
subclinical abnormalities in their middle ear functioning, mostly with type AS
tympanogram. Independent clinical predictors of S-MEM included previous head
injury, diabetes, history of osteoarthritis of knee joints, and absent acoustic
reflex.
PMID- 29937898
TI - Bowel injury following gynecological laparoscopic surgery.
AB - Background: Bowel injury remains a serious complication of gynecological
laparoscopic surgery. We aimed to review the literature on this topic, combined
with personal experiences, so as to give recommendations on how to avoid and
manage this complication. Methods: We performed a narrative review on bowel
injury following gynecological laparoscopic surgery using PubMed covering
prevention, diagnosis, and management. Search terms used were laparoscopy,
gynaecology, injury, bowel, prevention, treatment. Results: Important principles
of prevention include proper pre-operative evaluation and increased laparoscopic
surgical skills and knowledge. High clinical suspicion is crucial for early
diagnosis. Diagnostic workup of suspected cases includes serial abdominal
examination, measuring inflammatory markers, and performing imaging studies
including abdominal ultrasound and CT scan. When bowel injury is recognized
during the first laparoscopic procedure then laparoscopic primary suturing could
be tried although laparotomy may be needed. When diagnosis is delayed, then
laparotomy is the treatment of choice. The role of robotic surgery and three
dimensional laparoscopic gynecological surgery on bowel injury needs to be
further assessed. Conclusion: Early recognition of bowel injury is crucial for a
favorable clinical outcome. A combined collaboration between gynecologists and
general surgeons is important for timely and proper decisions to be made.
PMID- 29937899
TI - An erroneous opinion on a cause of death in a forensic autopsy: a case report.
AB - Background: The quality of autopsies is always questioned in courts, especially
in developing countries. Wrong decisions or misjudgments are undesirable in
medicine, but they are very dangerous in forensic medicine. If a wrong opinion is
given, either a culprit can be acquitted or an innocent person can be sentenced.
Therefore, an expert opinion is always required before the announcement of a
judgment. Objective: To highlight the problem of accuracy in determining the
cause of death in forensic autopsy. Case history: A 19- year old young adult male
(Mr E), who had a history of alcohol abuse, was brought to a hospital casualty
department by police, on an allegation of theft. He was unconscious and died
within two hours of arrival. A post-mortem report was requested by a private
attorney for an expert opinion. A post-mortem examination was conducted and
multiple superficial injuries were recorded on his body. Head injury was given as
a cause of death. The author seeks to critically analyze the post-mortem findings
in relation to the cause and manner of death. Conclusion: An erroneous opinion
was reached regarding cause and manner of death in this autopsy report.
PMID- 29937900
TI - HIV and NCDs: inevitable interaction in resource limited settings.
PMID- 29937901
TI - Serum procollagen type 1 N propeptide: A novel diagnostic test for diabetic foot
osteomyelitis - A case-control study.
AB - Background: The objective of the study was to determine whether serum levels of
procollagen type 1 N propeptide (P1NP), a bone formation turnover marker, differs
between diabetic foot ulcer with osteomyelitis (DFO) and diabetic foot ulcers
without osteomyelitis serving as controls. It was also aimed to assess the
usefulness of P1NP in diagnosing DFO compared to other common inflammatory
markers. Materials and Methods: A case-control study was designed comparing the
aforementioned groups. Patients were classified as osteomyelitis and controls
based on the International Working Group diagnostic criteria. Serum P1NP and
three other inflammatory markers, namely, C-reactive protein (CRP), white blood
cells (WBC), and platelets were analyzed on patients with DFO and controls.
Results: The mean serum P1NP levels were significantly higher in the DFO group
(n: 16), 10.5 +/- 5.2 (ng/ml), than the control group (n: 11) 3.1 +/- 2.8
(ng/ml), P = 0.001. P1NP showed the highest sensitivity/specificity 86.7%/80%
compared to 70.6%/80%, 56.2%/45.4%, and 50%/37% for CRP, WBC and platelets,
respectively. Receiver operator characteristic curves showed the best value of
area under the curve of 0.9 for P1NP compared to 0.85, 0.54, and 0.46 for CRP,
WBC, and platelets. Conclusion: We found marked elevation of serum P1NP in
diabetic foot ulcer with bone infection with potential value in using it to
diagnose DFO.
PMID- 29937903
TI - Medical diagnostic self-examination application: Applied medical informatics
technology for supporting primary self-care.
PMID- 29937902
TI - Doppler assessment of children with liver cirrhosis and portal hypertension in
comparison with a healthy control group: An analytical cross-sectional study.
AB - Background: Doppler ultrasonography (Doppler US) plays an important role in
evaluating patients with liver cirrhosis. This study aims to investigate the
hemodynamic alterations of hepatic artery and portal vein among children with
liver cirrhosis and portal hypertension (esophageal varices). Materials and
Methods: We conducted an analytical cross-sectional study in Imam Hossein
Children's Hospital, Isfahan, Iran, in 2016. A number of 33 cirrhotic children
with or without esophageal varices were selected through convenience sampling
method to be compared with 19 healthy children as controls using color and
spectral Doppler US. Results: Portal vein mean velocities were 15.03 +/- 7.3 cm/s
in cirrhotics, 16.47 +/- 6.4 cm/s in controls (P = 0.51), 11.6 +/- 4.7 cm/s in
patients with varices, and 17.9 +/- 7.3 cm/s in patients without varices (P =
0.015). Mean diameters of caudate lobe, portal vein, and splenic vein, as well as
the mean values of liver and spleen span, were significantly higher in cirrhotic
children. The frequency of flow reversal (hepatofugal flow) was not detected
significantly different in cirrhotics. Peak systolic velocity, end diastolic
velocity, pulsatility index, and resistive index for hepatic artery as well as
liver vascular index were not significantly different in cirrhotics in comparison
with controls. Conclusion: Alterations in Doppler parameters of portal vein
including diameter and velocity may be the helpful indicators of liver cirrhosis
and esophageal varices in children, respectively. Parameters of hepatic artery
may not differentiate children with liver cirrhosis.
PMID- 29937904
TI - HLA-DRB1 gene polymorphisms in Iranian children with Henoch-Schonlein purpura.
AB - Background: People of all ages can suffer from Henoch-Schonlein purpura (HSP),
but it is the most common vasculitis in childhood. The most important involving
gene is located on chromosome 6p21.3, a region coding for human leukocyte
antigens (HLAs). Among HLA genes, because of the high rate of polymorphisms, HLA
DRB1 is estimated to have a strong association with HSP. In this study, we aimed
to assess the association of HLA-DRB1 alleles with HSP in Iranian children.
Materials and Methods: This study consisted of thirty Iranian children with HSP
and 35 healthy controls. Genomic DNA was extracted, and HLA typing was performed
by polymerase chain reaction with sequence-specific primers technique. Results:
The results have shown that HLA-DRB1*01 and HLA-DRB1*11 (P = 0.002, odds ratio
[OR] = 7.579, confidence interval [CI] = 1.934-29.697 and P = 0.039, OR = 3.333,
CI = 1.030-10.788), respectively, are the most frequent alleles associated with
HSP in Iranian children population. The frequency of other alleles was not
significantly different in both groups. The results also show no correlation
between HLA types and disease manifestations. Conclusion: According to these
results, there is an association between HLA-DRB1*01 and HLA-DRB1*11 gene
polymorphisms and susceptibility to HSP in our study group.
PMID- 29937905
TI - Advanced glycation end products and risk of hypertension in Iranian adults:
Tehran lipid and glucose study.
AB - Background: Elevated blood pressure is still one of the major risk factors for
diseases and disabilities and also a public health challenge worldwide. In the
present longitudinal study, we aimed to evaluate the association between risk of
hypertension and dietary advanced glycation end products (AGEs) as a recently
discussed potential risk factor. Materials and Methods: Dietary assessment of
1775 participants in the third phase of Tehran lipid and glucose study to obtain
dietary intake of AGEs was performed using a validated semi-quantitative food
frequency questionnaire, and they were followed up for a mean duration of
approximately 6 years. To determine the incidence of hypertension across
quartiles of AGEs intake, logistic regression models with adjustment for
potential confounding variables were used. All statistical analyses were
conducted using SPSS, and P < 0.05 was considered statistically significant.
Results: Higher hypertension occurrence risk was generally attributed to higher
AGEs intake quartiles after adjusting for age in men (odds ratio [OR] = 1.48, 95%
confidence interval [CI] = 1.11-1.52, P = 0.038) and additional adjustment for
smoking, drugs, and physical activity in women (OR = 1.38%-95% CI = 1.09-1.42, P
= 0.042). Moreover, across the increasing trend of dietary AGEs intake, the
percentage of fat intake increased and that of carbohydrate significantly
decreased (P < 0.0001). Conclusion: In conclusion, it is highly recommended to
limit dietary AGEs consumption to prevent and manage hypertension and its
complications.
PMID- 29937906
TI - Retinol-binding protein 4 versus albuminuria as predictors of estimated
glomerular filtration rate decline in patients with type 2 diabetes.
AB - Background: Since the increase in some tubular damage biomarkers can be observed
at the early stage of diabetic nephropathy, even in the absence of albuminuria,
we aimed to investigate if urinary albumin is superior than tubular damage
marker, such as serum retinol-binding protein 4 (RBP4), in predicting renal
function decline (defined as estimated glomerular filtration rate [eGFR] <60
mL/min/1.73 m2) in the cohort of patients with type 2 diabetes mellitus (T2D).
Materials and Methods: A total of 106 sedentary T2D patients (mean [+/- standard
deviation] age 64.9 [+/-6.6] years) were included in this cross-sectional study.
Anthropometric and biochemical parameters (fasting glucose, glycated hemoglobin
[HbA1c], lipid parameters, creatinine, RBP4, high sensitivity C-reactive protein
[hsCRP], urinary albumin excretion [UAE]), as well as blood pressure were
obtained. Results: HsCRP (odds ratio [OR] =0.754, 95% confidence interval [CI]
(0.603-0.942), P = 0.013) and RBP4 (OR = 0.873, 95% CI [0.824-0.926], P < 0.001)
were independent predictors of eGFR decline. Moreover, although RBP4 and UAE as
single diagnostic parameters of renal impairment showed excellent clinical
accuracy (area under the curve [AUC] = 0.900 and AUC = 0.940, respectively), the
Model which included body mass index, HbA1c, triglycerides, hsCRP, and RBP4
showed statistically same accuracy as UAE, when UAE was used as a single
parameter (AUC = 0.932 vs. AUC = 0.940, respectively; P for AUC difference =
0.759). As well, the Model had higher sensitivity and specificity (92% and 90%,
respectively) than single predictors, RBP4, and UAE. Conclusion: Although serum
RBP4 showed excellent clinical accuracy, just like UAE, a combination of markers
of tubular damage, inflammation, and traditional markers has the higher
sensitivity and specificity than UAE alone for prediction renal impairment in
patients with T2D.
PMID- 29937907
TI - Full colonoscopy in patients under 50 years old with lower gastrointestinal
bleeding.
AB - Background: Lower gastrointestinal (GI) bleeding is a common clinical problem in
young patients. The management of this disease in patients is challenging. The
aim of this study is to compare sigmoidoscopy with full colonoscopy in these
patients. Materials and Methods: In this cross-sectional study, 120 eligible
patients under 50 years old with acute rectal bleeding were enrolled. After
cleaning the colon, initially the patients underwent sigmoidoscopy. Pain, the
comfort of the test by physician and patient, duration of the procedure, and
pathologic findings were recorded. The procedure continued until the splenic
flexure passed in the ileocecal valve, and this stage was considered as proximal
colonoscopy. Pain, easy performance by physician and the patient, duration of
procedure, and pathologic findings were recorded in this stage too. The variables
in the two stages were compared with each other. Results: There were 66 women
(55%) and 54 men (45%) and the mean of age was 41 +/- 7.9 years. Proximal
colonoscopy from splenic flexure to reach cecum was relatively easier for the
physician and the patient than sigmoidoscopy (P < 0.001). Furthermore, the time
spent to carry out proximal colonoscopy was less than the time taken for
sigmoidoscopy (P < 0.001). Pathologic findings recorded in full colonoscopy were
more than sigmoidoscopy (P < 0.001). Therefore, full colonoscopy that includes
sigmoidoscopy and proximal colonoscopy is relatively easier than sigmoidoscopy
for patients, and it also proves more advantageous than sigmoidoscopy for
physicians to perform in Iranian patients because of more tortuous and elongated
sigmoid colon in these patients. Conclusion: It is advised to perform full
colonoscopy than sigmoidoscopy in young patients with lower GI bleeding.
PMID- 29937908
TI - Hyperimmunoglobulin E syndrome.
PMID- 29937909
TI - The effect of FADS2 gene rs174583 polymorphism on desaturase activities, fatty
acid profile, insulin resistance, biochemical indices, and incidence of type 2
diabetes.
AB - Background: In this study, we investigated the associations of erythrocytes fatty
acid composition, activities of delta-5 desaturase (D5D) and delta-6 desaturase
(D6D), and other metabolic risk factors, with type 2 diabetes (T2D) risk to
determine if rs174583 polymorphism of FADS2 gene had any effect on these
associations. Materials and Methods: Fatty acid profile of erythrocytes was
determined using gas chromatography-mass spectrometry in 95 T2D patients and 95
apparently healthy participants. The genotypes of single-nucleotide polymorphism
(SNP) of FADS2 gene were determined using the polymerase chain reaction
restriction fragment length polymorphism technique. Other biochemical parameters
were measured in the serum using standard analytical procedures. Results: D6D
activity was increased (P < 0.001) and D5D activity was decreased in T2D patients
(P < 0.001) compared to controls. Homeostatic model assessment insulin resistance
(HOMA-IR) index was positively correlated with D6D (r = 0.34, P < 0.001) and
negatively correlated with D5D (r = -0.19, P = 0.02). Palmitic acid (P < 0.001)
and dihomo-gamma-linolenic acid (P = 0.03) were higher and linoleic acid (P <
0.001) and arachidonic acid (AA) (P < 0.001) were lower in T2D patients. The
distribution of rs174583 genotypes which includes C/T, C/C, and T/T was not
different in the two groups (P = 0.63). Conclusion: In the population studied,
there was a strong association in the erythrocytes fatty acid composition, D5D
and D6D activities and other metabolic risk factors between non-T2D and T2D
patients. In addition, there was a strong association in erythrocytes DGLA and AA
contents and D5D activities between rs174583 genotypes in all participants.
However, the distribution of rs174583 genotypes did not differ significantly
between T2D patient and controls, and it did not appear to be an association
between rs174583 SNP and incident of T2D.
PMID- 29937910
TI - Platelet distribution width as a novel indicator of disease activity in systemic
lupus erythematosus.
AB - Background: Significance of platelet distribution width (PDW) and mean platelet
volume (MPV) in assessing disease activity of systemic lupus erythematosus (SLE)
remains unclear. This study was aimed to evaluate PDW and MPV as potential
disease activity markers in adult SLE patients. Materials and Methods: A total of
204 study participants, including 91 SLE patients and 113 age- and gender-matched
healthy controls, were selected in this cross-sectional study. They were
classified into three groups: control group (n = 113), active SLE group (n = 54),
and inactive SLE group (n = 37). Demographic, clinical, and laboratory data were
analyzed. Results: In patient group, PDW was statistically higher than that in
control group (13.54 +/- 2.67 vs. 12.65 +/- 2.34, P = 0.012), and in active
group, PDW was significantly increased compared to inactive group (14.31 +/- 2.90
vs. 12.25 +/- 1.55, P < 0.001). However, MPV was significantly lower in SLE group
than in control group (10.74 +/- 0.94 vs. 11.09 +/- 1.14, P = 0.016). PDW was
positively correlated with SLE disease activity index (P < 0.001, r = 0.529) and
erythrocyte sedimentation rate (P = 0.002, r = 0.321) and negatively correlated
with C3 (P < 0.001, r = -0.419). However, there was no significant association
between MPV and these study variables. A PDW level of 11.85% was determined as a
predictive cutoff value of SLE diagnosis (sensitivity 76.9%, specificity 42.5%)
and 13.65% as cutoff of active stage (sensitivity 52.6%, specificity 85.3%).
Conclusion: This study first associates a higher PDW level with an increased SLE
activity, suggesting PDW as a novel indicator to monitor the activity of SLE.
PMID- 29937911
TI - Effects of DA-5513 on alcohol metabolism and alcoholic fatty liver in rats.
AB - Hangover is characterized by a number of unpleasant physical and mental symptoms
that occur after heavy alcohol drinking. In addition, consistently excessive
alcohol intake is considered as a major reason causes liver disease. The present
study investigated the in vivo effects of DA-5513 (Morning care(r) Kang Hwang) on
biological parameters relevant to hangover relief and alcoholic fatty liver.
Blood alcohol and acetaldehyde concentrations were determined in rats
administered a single dose of alcohol and treated with DA-5513 or commercially
available hangover relief beverages (Yeomyung(r) and Ukon(r)). The effects of DA
5513 on alcoholic fatty liver were also determined in rats fed alcohol-containing
Lieber-DeCarli diets for 4 weeks. Serum liver function markers (aspartate and
alanine aminotransferase activities) and serum/liver lipid levels were assessed.
Blood alcohol and acetaldehyde concentrations were lower in the groups treated
with DA-5513 or Yeomyung(r), as compared with control rats. However, Ukon(r) did
not produce any significant effects on these parameters. Treatment with DA-5513
significantly reduced serum aspartate and alanine aminotransferase activities and
markedly reduced serum cholesterol and triglyceride levels, as compared with
control rats. Histological observations using Oil Red O staining found that DA
5513 delayed the development of alcoholic fatty liver by reversing hepatic fat
accumulation. These findings suggest that DA-5513 could have a beneficial effect
on alcohol-induced hangovers and has the potential to ameliorate alcoholic fatty
liver.
PMID- 29937912
TI - Decrease in glucose transporter 1 levels and translocation of glucose transporter
3 in the dentate gyrus of C57BL/6 mice and gerbils with aging.
AB - In the present study, we compared the cell-specific expression and changes
protein levels in the glucose transporters (GLUTs) 1 and 3, the major GLUTs in
the mouse and gerbil brains using immunohistochemistry and Western blot analysis.
In both mouse and gerbils, GLUT1 immunoreactivity was mainly found in the blood
vessels in the dentate gyrus, while GLUT3 immunoreactivity was detected in the
subgranular zone and the molecular layer of the dentate gyrus. GLUT1
immunoreactivity in blood vessels and GLUT1 protein levels were significantly
decreased with age in the mice and gerbils, respectively. In addition, few GLUT3
immunoreactive cells were found in the subgranular zone in aged mice and gerbils,
but GLUT3-immunoreactivity was abundantly found in the polymorphic layer of
dentate gyrus in mice and gerbils with a dot-like pattern. Based on the double
immunofluorescence study, GLUT3-immunoreactive structures in gerbils were
localized in the glial fibrillary acidic protein-immunoreactive astrocytes in the
dentate gyrus. Western blot analysis showed that GLUT3 expression in the
hippocampal homogenates was slightly, although not significantly, decreased with
age in mice and gerbils, respectively. These results indicate that the reduction
in GLUT1 in the blood vessels of dentate gyrus and GLUT3 in the subgranular zone
of dentate gyrus may be associated with the decrease in uptake of glucose into
brain and neuroblasts in the dentate gyrus. In addition, the expression of GLUT3
in the astrocytes in polymorphic layer of dentate gyrus may be associated with
metabolic changes in glucose in aged hippocampus.
PMID- 29937913
TI - Effects of dietary lipid-coated zinc on the antioxidant defense system in the
small intestine and liver of piglets.
AB - The purpose of the study was to investigate the effects of lipid-coated ZnO (LCZ)
and the level of LCZ compared with ordinary zinc oxide (ZnO) on antioxidant
defense system in the intestine and liver of piglets. A total of forty piglets
(n=8) were fed a diet supplemented with 100 ppm Zn with ZnO (ZnO-1), 2,500 ppm Zn
with ZnO (ZnO-2), 100 ppm Zn as LCZ (LCZ-1), 200 ppm Zn as LCZ (LCZ-2), or 400
ppm Zn as LCZ (LCZ-3) for 14-d, respectively. The LCZ-3 group resulted in higher
(P<0.05) mRNA expressions and activities of CuZn-superoxide dismutase (SOD),
glutathione peroxidase (GPX), catalase (CAT), and glutathione S-transferase (GST)
in jejunal mucosa compared with the ZnO-1 and LCZ-1 groups, while no difference
was observed in the mRNA level of antioxidant genes between the ZnO-1 and ZnO-2
groups. Within the LCZ groups, the LCZ level linearly and quadratically (P<0.01)
increased antioxidant enzymes in the jejunum. The maximum response of jejunal
antioxidant enzymes to Zn supplementation was achieved by 400 ppm of LCZ. Hepatic
mRNA expression of antioxidant enzymes was unaffected by Zn source and level,
while hepatic SOD and GST activities were greater (P<0.05) in the LCZ-3 group
than in the ZnO-1 group. No difference was observed in lipid peroxidation of the
jejunum and liver and the total antioxidant power of plasma among groups. In
conclusion, a supplementation with 400 ppm of LCZ resulted in a maximum increase
in antioxidant enzymes, indicating that LCZ may affect antioxidant defense system
more profoundly than ZnO.
PMID- 29937914
TI - Anti-Helicobacter pylori activity and inhibition of gastritis by Allium hookeri
extract.
AB - Allium hookeri is widely consumed plant as a vegetable and herbal medicine in
southeastern Asia. Allium hookeri has been reported antioxidant, improvement of
bone health and antidiabetic effects. In the present study, we investigated the
potential inhibitory effect of Allium hookeri extract (AHE) on Helicobacter
pylori. The in vitro anti-bacterial activities of AHE were determined by disk
agar diffusion method. Also, the inhibition effect of the AHE on H. pylori
infection was investigated using a mouse model. H. pylori colonization was
confirmed by rapid urease tests, as described previously. Mucosal damage was
evaluated grossly and histologically according to previously described criteria.
As the results of the disk agar diffusion assay, CLR, AMX and MTZ inhibited the
bacterial growth with inhibition zone of 19.2, 15.2 and 7.5 mm, respectively. AHE
100 ug/mL showed an inhibition zone value of 20.6 mm. Rapid urease tests of the
mice stomachs demonstrated a significant reduction in H. pylori colonization. In
addition to the therapeutic effect against H. pylori infection, the AHE reduced
mucosal inflammation and epithelial damages in the stomach of H. pylori-infected
mice. These results demonstrate that the AHE successfully cured an H. pylori
infection and treated the H. pylori infection. This AHE could be a promising
treatment for patients with gastric complaints including gastritis caused by H.
pylori.
PMID- 29937915
TI - Elimination half-lives of interleukin-6 and cytokine-induced neutrophil
chemoattractant-1 synthesized in response to inflammatory stimulation in rats.
AB - The elimination half-lives of in Interleukin-6 (IL-6) and cytokine-induced
neutrophil chemoattractant-1 (CINC-1) in rats after inflammatory stimulation were
investigated. Five male Sprague-Dawley rats were used (age, 9 weeks; body weight,
235-375 g). Turpentine oil was intramuscularly injected at a dose of 2 mL/kg body
weight to induce acute inflammation. Blood was collected pre-injection and 6, 12,
24, 36, 48, 60, 72, 84, and 96 h after the turpentine oil injection. Serum
concentrations of IL-6, CINC-1, and alpha2-macroglobulin (alpha2M) were measured
by enzyme-linked immunosorbent assay. Half-lives were calculated as
0.693/elimination rate constant. The serum concentration of alpha2M peaked at 48
h after turpentine oil injection. Serum concentrations of IL-6 and CINC-1
increased and peaked at 12 and 24 h, respectively. The terminal elimination half
lives of IL-6 and CINC-1 were 15.5 and 29.9 h, respectively. The half-life of
CINC-1 was significantly longer than that of IL-6 (P=0.006). These results
suggested that these cytokines synthesized in response to inflammatory
stimulation were rapidly eliminated in rats. The serum concentrations of these
cytokines should be measured at an early stage if these cytokines will be used as
surrogate inflammatory markers instead of acute-phase proteins.
PMID- 29937916
TI - Retropharyngeal SOL: An unusual presentation of a multifaceted entity.
PMID- 29937917
TI - Cytologic features, immunocytochemical findings, and DNA ploidy in four rare
cases of epithelioid hemangioendothelioma involving effusions.
AB - Background: Epithelioid hemangioendothelioma (EHE) involving serous effusion is
extremely rare, and the diagnosis can be challenging. DNA ploidy quantitation of
EHE in effusion fluids has not been previously described in the English-language
literature. Methods: Specimens of cytological diagnosed with EHE in effusion
fluids between 2002 and 2009 were retrieved from the pathology files at MD
Anderson Cancer Center. A total of four cases of EHE involving or arising from
effusion fluids were found, and we reviewed cytospin, smears, cell block
sections, and immunostained slides. DNA image analysis for ploidy and
proliferation evaluation was performed on a destained, papanicolaou-stained slide
from each case. Results: The tumor cells were epithelioid with prominent
cytoplasmic vacuolization and intracytoplasmic inclusions, which could resemble
reactive mesothelial cells, mesothelioma, or adenocarcinoma. The tumor cells were
positive for endothelial markers. DNA image analysis in three of the four cases
revealed predominantly diploid and tetraploid subpopulations, with few aneuploid
cells and fairly low proliferation indices, and these patients had fairly
prolonged survival. Conclusions: DNA image analysis is useful for differentiating
EHE from reactive mesothelial cells and high-grade carcinoma. For accurate
diagnosis of EHE in effusion fluids, cytologic features should be considered
together with clinical history and ancillary studies.
PMID- 29937919
TI - Episodic creep events on the San Andreas Fault caused by pore-pressure
variations.
AB - Recent seismic and geodetic observations indicate that interseismic creep rate
varies in both time and space. The spatial extent of creep pinpoints locked
asperities, while its temporary accelerations, known as slow-slip events, may
trigger earthquakes. Although the conditions promoting fault creep are well
studied, the mechanisms for initiating episodic slow-slip events are enigmatic.
Here we investigate surface deformation measured by radar interferometry along
the central San Andreas Fault between 2003 and 2010 to constrain the temporal
evolution of creep. We show that slow-slip events are ensembles of localized
creep bursts that aseismically rupture isolated fault compartments. Using a rate
and state friction model, we show that effective normal stress is temporally
variable on the fault, and support this using seismic observations. We propose
that, compaction-driven elevated pore fluid pressure in hydraulically isolated
fault zone and subsequent frictional dilation cause the observed slow slip
episodes. We further suggest that the 2004 Mw6 Parkfield earthquake might have
been triggered by a slow-slip event, which increased the Coulomb failure stress
by up to 0.45 bar per year. This implies that while creeping segments are
suggested to act as seismic rupture barriers, slow-slip events on these zones
might promote seismicity on adjacent locked segments.
PMID- 29937920
TI - Native Seed Supply and the Restoration Species Pool.
AB - Globally, annual expenditure on ecological restoration of degraded areas for
habitat improvement and biodiversity conservation is approximately $18bn. Seed
farming of native plant species is crucial to meet restoration goals, but may be
stymied by the disconnection of academic research in seed science and the lack of
effective policies that regulate native seed production/supply. To illustrate
this problem, we identified 1,122 plant species important for European grasslands
of conservation concern and found that only 32% have both fundamental seed
germination data available and can be purchased as seed. The "restoration species
pool," or set of species available in practice, acts as a significant
biodiversity selection filter for species use in restoration projects. For
improvement, we propose: (1) substantial expansion of research and development on
native seed quality, viability, and production; (2) open-source knowledge
transfer between sectors; and (3) creation of supportive policy intended to
stimulate demand for biodiverse seed.
PMID- 29937918
TI - Innate immune receptors drive dengue virus immune activation and disease.
AB - Dengue is a worldwide disease with 400 million annual infections that can lead to
septic shock and viral hemorrhagic fever with internal bleeding. These symptoms
are the result of uncontrolled immune activation. Macrophages and dendritic cells
are the main target of dengue virus (DENV) and the cellular source of cytokines
associated with this immune activation. Macrophages and dendritic cells express
several innate immune receptors that have been implicated in DENV immune
activation, of which, CLEC5A, RIG-I and MDA5 are most important. Notably,
activation of these receptors have profound effects on adaptive immune responses
against DENV. This review will focus on how innate immune receptors drive DENV
immune activation by inducing inflammatory cytokines and by activating adaptive
immune responses.
PMID- 29937921
TI - Contribution of volatile organic compound fluxes to the ecosystem carbon budget
of a poplar short-rotation plantation.
AB - Biogenic volatile organic compounds (BVOCs) are major precursors of both ozone
and secondary organic aerosols (SOA) in the troposphere and represent a non
negligible portion of the carbon fixed by primary producers, but long-term
ecosystem-scale measurements of their exchanges with the atmosphere are lacking.
In this study, the fluxes of 46 ions corresponding to 36 BVOCs were continuously
monitored along with the exchanges of mass (carbon dioxide and water vapor) and
energy (sensible and latent heat) for an entire year in a poplar (Populus) short
rotation crop (SRC), using the eddy covariance methodology. BVOC emissions mainly
consisted of isoprene, acetic acid, and methanol. Total net BVOC emissions were
19.20 kg C ha-1 yr-1, which represented 0.63% of the net ecosystem exchange
(NEE), resulting from -23.59 Mg C ha-1 yr-1 fixed as CO 2 and 20.55 Mg C ha-1 yr
1 respired as CO 2 from the ecosystem. Isoprene emissions represented 0.293% of
NEE, being emitted at a ratio of 1 : 1709 mol isoprene per mol of CO 2 fixed.
Based on annual ecosystem-scale measurements, this study quantified for the first
time that BVOC carbon emissions were lower than previously estimated in other
studies (0.5-2% of NEE) on poplar trees. Furthermore, the seasonal and diurnal
emission patterns of isoprene, methanol, and other BVOCs provided a better
interpretation of the relationships with ecosystem CO 2 and water vapor fluxes,
with air temperature, vapor pressure deficit, and photosynthetic photon flux
density.
PMID- 29937922
TI - Considering climate in studies of fertility and reproductive health in poor
countries.
AB - Understanding the links between climate and fertility and reproductive health
outcomes in poor countries is a major ethical and policy imperative. However,
doing so will require researchers in population sciences and in earth and climate
sciences to merge their expertise. To this end, the dominant theoretical
frameworks and readily available geospatial population data used by social
scientists provide a starting point for climate and physical scientists to think
about the mechanisms that link climate and weather to fertility and reproductive
health, and available climate data and analytic strategies can be used to develop
research that considers different scales of influence.
PMID- 29937923
TI - Religious Beliefs and Depression: Psychosocial Factors Affecting HIV Treatment
Outcomes in South Africa.
AB - Analyzing factors associated with virological failure (VF) may improve
antiretroviral therapy (ART) outcomes for individuals living with HIV. The Risk
Factors for Virological Failure (RFVF) study compared 158 cases with VF (viral
load, VL, >1,000 copies/mL) and 300 controls with virological suppression (VL
<=1,000 copies/mL) after >=5 months on their first ART regimen at McCord Hospital
in Durban, South Africa between October 2010 and June 2012. RFVF participants
completed a battery of various psychosocial measures. Using multivariate logistic
regression stratified for gender, the association of various psychosocial factors
with VF was assessed. It was found that not all factors were equally significant
for both genders. The factors that were significantly associated with VF for both
genders were younger age, shorter treatment duration and reporting depressive
symptoms. The factors associated with VF that differed by gender were religious
inactivity, having HIV+ family members, and status disclosure to friends.
PMID- 29937924
TI - A quantitative proteomic response of hepatocellular carcinoma Hep3B cells to
danusertib, a pan-Aurora kinase inhibitor.
AB - Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, but the
overall prognosis remains disappointing especially in the advanced-stage
patients. Aberration expression of Aurora kinases is tumorigenic and thus it has
attracted interests as therapeutic targets in cancer treatment. Here, we
investigated the proteomic response of HCC Hep3B cells to danusertib (Danu), a
pan-Aurora kinase inhibitor, and then validated the proteomic results based on
stable-isotope labeling by amino acids in cell culture (SILAC). The proteomic
data identified that Danu modulated the expression of 542 protein molecules (279
up-regulated; 260 down-regulated; 3 stable). Ingenuity pathway analysis (IPA) and
KEGG pathway analysis identified 107 and 24 signaling pathways were regulated by
Danu, respectively. IPA analysis showed cellular growth and proliferation, and
cell death and survival were among the top five molecular and cellular functions
regulated by Danu. The verification experiments showed that Danu inhibited the
proliferation of Hep3B cells with a 24-hr IC50 value of 22.03 uM. Danu treatment
also arrested Hep3B cells in G2/M phase via regulating the expression of key cell
cycle regulators and induced apoptosis via mitochondria-dependent pathway in a
dose-dependent manner. Besides, Danu induced a marked autophagy, and inhibition
of autophagy enhanced the anticancer effects of Danu, indicating a cyto
protective role of Danu-induced autophagy. Our proteomic data and Western
blotting assays showed the PI3K/Akt/mTOR signaling pathway was involved in the
inducing effect of Danu on apoptosis and autophagy. Collectively, our findings
have demonstrated that the Aurora kinases inhibition with danusertib results in
global proteomic response and exerts anticancer effects in Hep3B cells involving
regulation of cell cycle, apoptosis and autophagy and associated signaling
pathways.
PMID- 29937926
TI - Copy number variation and high expression of DNA topoisomerase II alpha predict
worse prognosis of cancer: a meta-analysis.
AB - Background: Increasing numbers of literatures have investigated the association
between TOP2A and cancer prognosis. But the results of the relationship between
the two were inconclusive. The aim of this meta-analysis was to elucidate whether
TOP2A could predict prognosis of cancer. Materials and Methods: A systematically
searching for potentially valuable literature was conducted through electronic
databases containing PubMed and Web of Science. Hazard Ratio (HR) and their 95%
confidence interval (CI) were used to assess the strength of association between
TOP2A and cancer prognosis. Results: Finally twenty-five studies were included in
this meta-analysis. High expression of TOP2A was associated with shorter disease
free survival (DFS) of cancer prognosis compared with low expression of TOP2A
(HR= 1.36, 95% CI= 1.18-1.57, P<0.001). Amplification of TOP2A gene showed no
significant association with overall survival (OS), disease free survival (DFS)
or relapse free survival (RFS) compared with non-amplification of TOP2A (OS: HR=
0.96, 95%CI= 0.75-1.22, P= 0.735; DFS: HR= 0.93, 95%CI= 0.70-1.23, P= 0.621; RFS:
HR= 0.97, 95%CI= 0.71-1.34, P= 0.867). In the subgroup of regions, TOP2A
amplification was associated with longer overall survival (HR= 0.66, 95%CI= 0.46
0.96, P= 0.029) in Australia. Alteration (amplification or deletion) of TOP2A
gene demonstrated shorter survival according to OS and RFS compared with those
with normal TOP2A status (OS: HR= 1.37, 95%CI= 1.22-1.55, P<0.001; RFS: HR= 1.26,
95%CI= 1.12-1.41, P<0.001). Conclusion: High TOP2A expression suggested
significant relationship with worse cancer prognosis. Alteration (amplification
or deletion) of TOP2A gene was also significantly related to shorter survival of
cancer patients. Therefore, TOP2A might be used as an indicator for poor
prognosis of cancer in the future.
PMID- 29937925
TI - Histone methylation in DNA repair and clinical practice: new findings during the
past 5-years.
AB - DNA double-strand breaks (DSBs) are highly toxic lesions that can impair cellular
homeostasis and genome stability to result in tumorigenesis for inappropriate
repair. Although DSBs are repaired by homologous recombination (HR) or non
homologous end-joining (NHEJ), the related mechanisms are still incompletely
unclear. Indeed, more and more evidences indicate that the methylation of histone
lysine has an important role in choosing the pathways of DNA repair. For example,
tri-methylated H3K36 is required for HR repair, while di-methylated H4K20 can
recruit 53BP1 for NHEJ repair. Here, we reviewed the recent progress in the
molecular mechanisms by which histone methylation functions in DNA double-strand
breaks repair (DSBR). The insight into the mechanisms of histone methylation
repairing DNA damage will supply important cues for clinical cancer treatment.
PMID- 29937927
TI - Assessment of the Long-term Diagnostic Performance of a New Serological Screening
Scheme in Large-scale Nasopharyngeal Carcinoma Screening.
AB - Background: Nasopharyngeal carcinoma (NPC) remains as a major public health
burden in Southern China. Over the last decade, Epstein-Barr virus (EBV)
serological detection has been the most promising tool used for NPC screening.
The present study aims to evaluate the long-term diagnostic performance of a new
NPC screening scheme (probability of NPC units [logit P], PROB>=0.65), and
compare this with other EBV seromarkers used within 2009-2015. Methods: Enzyme
linked immunosorbent assay (ELISA) for EBV capsid antigen (VCA/IgA) and nuclear
antigen-1 (EBNA1/IgA) was performed in 16,712 subjects, who were within 30-59
years old.All subjects were followed up for six years. The area under the
receiver operating characteristic curve (AUC) and correlation analyses were
preformed to evaluate the diagnostic value of different measures. Furthermore,
the rates of early diagnosis in NPC patients were statistically analyzed.
Results: The new NPC screening scheme (PROB>=0.65) and the four strategies
(VCA/IgA, EBNA1/IgA, VCA/IgA and EBNA1/IgA, and VCA/IgA or EBNA1/IgA) had
comparable rates of early diagnosis for NPC (no significant difference was
found), but the sensitivity of the new scheme (95.7%) was higher than that of the
others. The top three seromarkers with the largest AUC were PROB>=0.65
(AUC:0.926, 95% CI: 0.885-0.966), VCA/IgA or EBNA1/IgA (AUC:0.883, 95% CI:0.824
0.942), and EBNA1/IgA (AUC: 0.866, 95% CI: 0.794-0.938). Conclusion: The new NPC
screening scheme (PROB>=0.65) based on VCA/IgA and EBNA1/IgA outperforms the
other seromarkers, and making it the preferred serodiagnostic strategy for long
term NPC screening in high-incidence areas.
PMID- 29937928
TI - A Nomogram for Distinction and Potential Prediction of Liver Metastasis in Breast
Cancer Patients.
AB - Liver metastasis from breast cancer has poor prognosis. We aimed at developing a
reliable tool for making a distinction and prediction for liver metastasis in
breast cancer patients, thus helping clinical diagnosis and treatment. In this
study, totally 6238 patients from SEER database with known distant metastasis
status and clinicopathologic variables were enrolled and divided randomly into
training and validating groups. Logistic regression was used to screen variables
and a nomogram was constructed. After multivariate logistic regression, sex,
histology type, N stage, grade, age, ER, PR, HER2 status as significant variables
for constructing the nomogram. The nomogram for distinguishing and predicting
liver metastasis in breast cancer passed the calibration and validation steps and
the areas under the receiver operating characteristic curve of the training set
and the validation set were 0.6602 and 0.6511 respectively. Our nomogram is a
reliable and robust tool for the distinction and prediction of liver metastasis
in breast cancer patients, thus helping better choose medical examinations and
optimize therapeutic regimen under the cooperation among medical oncologists and
surgeons.
PMID- 29937929
TI - A Prognostic Nomogram Incorporating Depth of Tumor Invasion to Predict Long-term
Overall Survival for Tongue Squamous Cell Carcinoma With R0 Resection.
AB - Purpose: To establish a useful prognostic nomogram to predict long-term overall
survival for patients with tongue squamous cell carcinoma (TSCC) after R0
resection. Patients and Methods: The nomogram was developed using a retrospective
cohort of 235 TSCC patients from Sun Yat-sen University Cancer Center between 1
January 2000 and 31 December 2007. An independent dataset of 223 patients was
used for external validation. Multivariate Cox proportional hazards model
(backward selection; the Akaike information criteria) was applied to select
variables for construction of the nomogram. Discrimination and calibration were
performed using the area under the receiver operating characteristic (ROC) curve
(AUC) and calibration plots. Results: Using the backward selection of clinically
relevant variables, depth of invasion (hazard ratio [HR], 3.55; P < 0.001), pN
(HR, 3.48; P = 0.01), age (HR, 1.03; P < 0.01) and neck dissection (HR, 0.53; P =
0.04) were selected as independent predictive factors of survival. A nomogram was
thus established to predict survival of TSCC patients after R0 resection. The
calibration curve demonstrated that the nomogram was able to accurately predict 5
year overall survival (OS). In addition, our data showed the AUC of the nomogram
were 0.78 and 0.71 based on the internal and external validation, which were
significantly better than the 7th TNM stage (0.64/0.55). Conclusion: The proposed
nomogram resulted in accurate prognostic prediction of the 5-year OS for TSCC
patients with R0 resection.
PMID- 29937930
TI - Methylation patterns of RASA3 associated with clinicopathological factors in
hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is the sixth most common tumor worldwide. The
relationship between the gene methylation accumulation and HCC has been widely
studied. In our study, we used the Sequenom EpiTYPER assay to investigate the
methylation levels of the RASA3 in 164 HCC samples and paired adjacent non
cancerous tissues, and the association between methylation level and
clinicopathological features. The methylation level of the RASA3 in HCC samples
was found significantly lower than that in the adjacent non-cancerous tissues
(P<0.0001). Moreover, the hypomethylation of RASA3 in HCC samples was connected
with the presence of tumornecrosis (P=0.029) and alcohol intake (P=0.002).
Furthermore, it was found that the expression of RASA3 was significantly
decreased in tumor tissues (P=0.0053), which was also correlated with the
methylation levels of RASA3 gene. Thus, RASA3 hypomethylation is a common feature
in HCC, and may be a potential mechanism for HCC development, and serves as a
useful biomarker for the early detection, especially in alcohol-associated HCCs.
PMID- 29937931
TI - Angiotensin-converting Enzyme Inhibitors Decrease the Incidence of Radiation
induced Pneumonitis Among Lung Cancer Patients: A Systematic Review and Meta
analysis.
AB - Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin
receptor blockers (ARBs) have been demonstrated to mitigate radiation-induced
lung damage in animal models and preclinical studies. Our study aims to evaluate
whether ACEIs or ARBs reduce the incidence of radiation-induced pneumonitis (RP)
in lung cancer patients. Methods: Publications were searched from EMBASE, PubMed
and Web of Science databases. Seven studies published from April 2000 to August
2016 met inclusion criteria and included 1412 patients in total. Only patients
with grade 2 and above pneumonitis within 12 months after radiotherapy were
analyzed. Results: Patients taking ACEIs had a lower risk of developing radiation
pneumonitis compared with non-users (OR = 0.46, 95%CI = 0.31-0.67, p < 0.0001).
While the use of ARBs couldn't reduce the incidence of RP (OR = 1.42, 95%CI =
0.94-2.14, p = 0.10). Elderly patients (age >= 70) benefited more from ACEIs (OR
= 0.12, 95%CI = 0.02-0.67, p = 0.02). In addition, smokers were found to have a
lower risk of developing RP than non-smokers (OR = 0.49, 95%CI = 0.30-0.81, p =
0.005), but sex and the use of statin or NSAID had no influence on the appearance
of RP (p = 0.59, p = 0.70, p = 0.40, respectively). Conclusions: ACE inhibitors
could decrease the incidence of symptomatic RP among lung cancer patients.
However, the use of ARBs has a slight trend to develop RP but not above
statistical significance. Elderly patients (age >= 70) benefited the most from
ACEIs.
PMID- 29937932
TI - Combined Use of the Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios as a
Prognostic Predictor in Patients with Operable Soft Tissue Sarcoma.
AB - Background: Preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to
lymphocyte ratio (PLR) are associated with poor prognosis in soft tissue sarcoma
(STS). The aim of the present study is to determine whether the combination of
NLR and PLR (CNP) can better predict patient survival after resection for STS.
Methods: We included 310 STS patients in this retrospective study. Preoperative
CNP was calculated as follows: patients with both elevated NLR (>2.51) and PLR
(>191.1) were given a score of 2; patients showing an increase in one or neither
were allocated a score of 1 or 0, respectively. Results: Cut-off values of 2.51
and 191.1 were defined as elevated NLR and PLR, respectively. Elevated CNP was
significantly associated with older age (P=0.034), larger tumor size (P=0.025),
deeper tumor location (P=0.044), higher tumor grade (P=0.028), a more advanced
stage according to the American Joint Committee on Cancer (AJCC) (P=0.005),
shorter overall survival (OS) (P=0.000) and shorter disease-free survival (DFS)
(P=0.000). Multivariate analysis indicated CNP but not NLR or PLR to be an
independent prognostic factor for OS and DFS (P=0.000 and P=0.001, respectively).
Conclusions: Preoperative CNP is associated with tumor progression and can be
considered an independent marker of postoperative survival in patients with STS.
PMID- 29937933
TI - Current Smoking has a Detrimental Effect on Survival for Epidermal Growth Factor
Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) negative Advanced non
squamous Non-small Cell Lung Cancer (NSCLC) Patients Treated with Pemetrexed
Continuation Maintenance.
AB - Objectives: The aim of this study is to investigate the predictive value of
smoking history on treatment outcomes of pemetrexed continuation maintenance
therapy in advanced non-squamous NSCLC patients without EGFR mutations and ALK
rearrangements. Methods: 71 consecutive EGFR and ALK negative advanced non
squamous NSCLC patients who had received pemetrexed continuation maintenance
therapy at least two cycles were retrospectively analyzed in our single center.
The enrolled patients were categorized into two groups as never-/former light
smokers and current smokers according to their smoking history. Results: In the
71 non-squamous NSCLC patients, 30 (42.3%) were never-/former light smokers and
41 (57.7%) were current smokers. The objective response rate (ORR) of never
/former light smokers was significantly higher than that of current smokers
(26.7% vs. 7.3%, p = 0.026). Never-/former light smokers showed significantly
longer progression free survival (PFS) (6.6 [95% CI 5.3-7.9] months vs. 5.1 [95%
CI 3.5-6.7] months; HR: 0.557, 95% CI 0.339-0.915, p = 0.021) and overall
survival (OS) (17.3 [95% CI 14.4-20.2] months vs. 15.7 [95% CI 12.0-19.4] months;
HR: 0.578, 95% CI 0.338-0.986, p = 0.044) than current smokers. Multivariate
analysis identified smoking history was an independent predictive factor for PFS
and OS. Conclusions: Current smoking is an independent negative predictive factor
of outcomes for pemetrexed continuation maintenance therapy in advanced non
squamous NSCLC patients without EGFR mutations and ALK rearrangements.
PMID- 29937935
TI - Long non-coding RNA CDKN2B antisense RNA 1 gene inhibits Gemcitabine sensitivity
in bladder urothelial carcinoma.
AB - Objective: To investigate the clinical significance of long noncoding RNA
(lncRNA) CDKN2B antisense RNA 1 (CDKN2B-AS) gene and its effects on Gemcitabine
sensitivity in BUC. Materials and Methods: The expression of CDKN2B-AS gene was
examined with real-time quantitative PCR. The cell proliferation and the half
maximal inhibitory concentration (IC50) of Gemcitabine were detected with
enhanced CCK-8 assay. The apoptosis rate was examined using Annexin V-FITC/PI
double-staining apoptosis kit. The protein expression was examined with western
blotting. The activity of Wnt signaling pathway was examined with TOP/FOP
luciferase assay. Results: CDKN2B-AS gene was high-expressed in BUC tissues and
J82, T24 cells compared with paracancerous normal urothelial tissues and SV-HUC-1
cells. Furthermore, the high-expression of CDKN2B-AS gene was related with high
pathological grade and low Gemcitabine sensitivity of BUC tissues. The expression
of CDKN2B-AS gene in Gemcitabine-resistant T24/Gem cells was much higher than
that in T24 cells. Knockdown of CDKN2B-AS gene sensitized T24/Gem cells to
Gemcitabine, promoted Gemcitabine-induced cytotoxicity. Knockdown of CDKN2B-AS
gene inactivated Wnt signaling pathway, and Wnt signaling pathway mediated the
effects on Gemcitabine sensitivity induced by CDKN2B-AS knockdown in T24/Gem
cells. Conclusion: LncRNA CDKN2B-AS is high-expressed in BUC and related to low
Gemcitabine sensitivity of BUC. CDKN2B-AS inhibited Gemcitabine sensitivity
through Wnt signaling pathway in BUC.
PMID- 29937934
TI - MicroRNA-30b targets Snail to impede epithelial-mesenchymal transition in
pancreatic cancer stem cells.
AB - Snail-mediated epithelial-mesenchymal transition (EMT) process plays a
fundamental role in facilitating pancreatic ductal adenocarcinoma (PDAC) stemness
and metastasis. In the present study, we revealed that microRNA-30 (miR-30)
members, especially miR-30b, were remarkably downregulated in triple-positive
(CD24+, CD44+, EpCAM+) pancreatic cancer stem cells (PCSCs). In addition, we
revealed that miR-30b suppressed EMT process in PCSCs. Overexpression of miR-30b
led to reduced expression of mesenchymal marker N-cadherin and the upregulation
of epithelial marker E-cadherin. Moreover, both of TargetScan and PicTar
algorithms predicted that miR-30b directly targeted Snail 3'UTR. Luciferase
reporter assay showed that miR-30b could specifically reduce the translational
activity of Snail wild-type 3'UTR, but not its mutant form. In line with these
results, transwell assay demonstrated that overexpression of miR-30b mimic
impaired migratory and invasive capacities of PCSCs. Furthermore, miR-30b
overexpression suppresses in vivo tumorigenic potential of PDACs. Finally, a
negative correlation between the expression of miR-30b and Snail was uncovered.
Low level of miR-30b and high Snail expression both predict dismal prognosis in
PDAC patients. Taken together, these findings implicate that miR-30b may suppress
PCSC phenotype and PDAC metastasis through posttranscriptionally suppressing
Snail expression, highlighting that miR-30b may serve as a therapeutic agent in
the treatment of PDAC.
PMID- 29937936
TI - Does the Preoperative Prognostic Nutritional Index Predict Survival in Patients
with Liver Metastases from Colorectal Cancer Who Underwent Curative Resection?
AB - Purpose: The prognostic nutritional index (PNI) has been correlated with long
term outcomes in various cancer patients. However, the relationship between the
PNI and long-term outcomes in patients with colorectal cancer liver metastasis
(CRLM) who have undergone liver surgery have not been fully investigated. In this
study, we aimed to identify the impact of the preoperative PNI on the long-term
oncologic outcomes of patients with CRLM who have undergone curative hepatic
resection. Methods: A total of 243 CRLM patients who underwent curative hepatic
resection for liver metastases in the Sun Yat-sen University Cancer Center
between September 1999 and July 2015 were enrolled, and their medical records
were analyzed retrospectively. The preoperative PNI was calculated as 10* the
serum albumin concentration (g/dL) + 0.005 * the total lymphocyte count (per
mm3). The PNI was compared according to the statuses of clinicopathological
features. In addition, the regression-free survival (RFS) and overall survival
(OS) were analyzed according to the preoperative PNI using univariate and
multivariate analyses. Results: The optimal cut-off value of the preoperative PNI
was set at 48.5 using the X-tile software. Older patients and those who had
undergone synchronous hepatic resection were more likely to belong to the low PNI
group (<=48.5) (all P < 0.05). In multivariate analyses, PNI > 48.5 was
associated with markedly better survival outcomes as an independent factor, both
for OS and RFS. Conclusion: For patients with CRLM undergoing curative hepatic
resection, preoperative PNI is a simple and efficient indicator (cut-off
value=48.5) for preoperative estimation of oncologic outcomes.
PMID- 29937937
TI - AMPH-1 is critical for breast cancer progression.
AB - Amphiphysin 1 (AMPH-1) is a nerve terminals-enriched protein involved in
endocytosis, and we observe that its expression is increased in breast cancer
tumor in compared with normal breast. However, its function in breast cancer is
unknown. Here we aim to explore the role of AMPH-1 in breast cancer cells.
Knockdown of AMPH-1 in breast cancer cells promotes cell proliferation, cell
cycle progression and cell migration, and attenuates cell apoptosis. Of note,
knockdown of AMPH-1 promotes breast cancer progression in xenograft mouse model.
These oncogenic phenotypes may be partially due to the activated EMT and ERK
pathways after inhibition of AMPH-1. Oncomine analyses of multiple breast cancer
patient datasets show that reduced AMPH-1 mRNA level is significantly associated
with breast cancer patients having metastatic events, advanced stage, poor
clinical outcomes, and Paclitaxel+FEC treatment resistance. In summary, our
results identified the anti-oncogenic function of AMPH-1 in breast cancer in
vitro and in vivo. Activation of AMPH-1 may be a promising approach to treat
breast cancer patients.
PMID- 29937938
TI - Unique Responses of Hepatocellular Carcinoma and Cholangiocarcinoma Cell Lines
toward Cantharidin and Norcantharidin.
AB - The present study aimed to investigate whether cell lines from human gastric and
liver cancers respond differently toward cantharidin (CTD) and norcantharidin
(NCTD) than other types of cancer cells. We first established the half maximal
inhibitory concentrations (IC50s) of CTD for a large panel of cancer cell lines
representing the 12 major types of human cancers and the mode of cell death
induced by the two compounds. We next compared the growth inhibitory effects as
well as the corresponding modes of action of CTD and NCTD. The IncuCyte ZOOM
system was used as a semi-high throughput means to define IC50s and 90%
inhibitory doses (IC90s) as a reference for the maximal tolerable doses (MTDs)
for the two compounds in 72 cancer cell lines. Classical clonogenic survival
assay was used to assess the anti-proliferative effect of CTD on selected cell
lines of interest. In addition, DNA content-based flow was used to interrogate
the modes of cell death following CTD or NCTD exposure. The results of these
experiments led to several findings. 1). Cell lines representing hepatocellular
carcinomas (HCCs) and cholangiocarcinomas (CCs) were among the most sensitive
toward CTD, consistent with the previous clinical study of this compound and its
source of origin, Mylabris. 2). Among the individual cell lines of a given cancer
types, the sensitivity trends for CTD and NCTD did not exhibit a good
correlation. 3) CTD and NCTD caused distinctive cytotoxic effects on HepG2 cells.
Specifically, while a cytostatic effect is the primary cause of growth inhibition
of CTD, cytotoxic effect is the main contributing factor for the growth
inhibition of NTCD. These results indicate that liver cancer cell lines are among
the most sensitive to CTD and that CTD and NCTD exhibit their effects through
distinct mechanisms.
PMID- 29937939
TI - Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated
Immune Response in Prostate Cancer.
AB - Introduction: The androgen receptor (AR) regulates immune-related epithelial-to
mesenchymal transition (EMT), and prostate cancer (PCa) metastasis. Primary tumor
infiltrating lymphocytes (TILs) [CD3+, CD4+, and CD8+ TILs] are potential
prognostic indicators in PCa, and variations may contribute to racial disparities
in tumor biology and PCa outcomes. Aim: To assess the technical feasibility of
tumor microarray (TMA)-based methods to perform multi-marker TIL profiling in
primary resected PCa. Methods: Paraffin-embedded tissue cores of
histopathologically-confirmed primary PCa (n = 40; 1 TMA tissue specimen loss)
were arrayed in triplicate on TMAs. Expression profiles of AR, CD3+, CD4+, and
CD8+ TILs in normal prostate, and the center and periphery of both the tumor
dominant nodule and highest Gleason grade were detected by IHC and associated
with clinical and pathological data using standard statistical methodology. An
independent pathologist, blinded to the clinical data, scored all samples
(percent and intensity of positive cells). Results: TMAs were constructed from 21
(53.8%) Black and 18 (46.2%) White males with completely-resected, primarily pT2
stage PCa [pT2a (n = 3; 7.7%); pT2b (n = 2; 5.1%); pT2c (n = 27; 69.2%); pT3a (n
= 5; 12.8%); mean pre-op PSA = 8.17 ng/ml]. The CD3, CD4, CD8, and CD8/CD3
cellular protein expression differed from normal in the periphery of the dominant
nodule, the center of the highest Gleason grade, and the periphery of the highest
Gleason grade (P < 0.05). Correlations between TIL expression in the center and
periphery of the dominant nodule, with corresponding center and periphery of the
highest Gleason grade, respectively, were robust, and the magnitude of these
correlations differed markedly by race (P < 0.05). Conclusions: Multi-marker (AR,
CD3, CD4, CD8) profiling with IHC analysis of TMAs consisting of primary, non
metastatic resected prostate cancer is technically feasible in this pilot study.
Future studies will evaluate primary tumor immunoscore using semi-quantitative,
IHC-based methodology to assess differences in the spectrum, quantity, and/or
localization of TILs, and to gain insights into racial disparities in PCa tumor
biology and clinical outcomes.
PMID- 29937940
TI - Predicting hepatocellular carcinoma development for cirrhosis patients via
methylation detection of heparocarcinogenesis-related genes.
AB - Background: Most hepatocellular carcinoma (HCC) patients have undergone a
progression from chronic hepatitis, then liver cirrhosis (LC), and finally to
carcinoma. The objective of this study was to elucidate risk factors to predict
HCC development for cirrhosis patients. Methods: Multiple methylated specific PCR
(MSP) was applied to determine methylation status of heparocarcinogenesis-related
genes in 396 tissue and plasma specimens and multivariate cox model was used to
analyze the relationship between risk variables and HCC development among
cirrhosis patients, followed up in a median period of 30 months. Results: Among
105 LC cases, HCC incidence rate at 30 months was 30.48% (32/105), which were
statistically associated with patients' age and aberrant methylation of p16,
SFRP, and LINE1 (p<0.05). Receiver operating characteristic (ROC) curve showed
the overall predictive accuracy reached the highest (90.7%) if the four risk
variables were concurrent to predict HCC development. Moreover, along with the
growth of age from 0-40, 40-55, to 55-70 years or the increased number of
aberrantly-methylated gene from 0-1 to 2-3, the HCC incidence rate of cirrhosis
patients rised from 10.00%, 12.28% to 82.14% and 17.44% to 89.47%, separately.
Thus, based on combined analysis with diverse age and number of aberrantly
methylated gene, 105 cases were divided into five groups and computed their
respective HCC incidecne rate to categorize them into different risk groups. Of
note, A significant lifting of HCC incidence rate in the high-risk group (40-55
years coupled with 2-3 aberrantly-methylated genes, 55-70 years coupled with 0-1
aberrantly-methylated gene, 55-70 years coupled with 2-3 aberrantly-methylated
genes; n=33) was observed compared with the low-risk group (0-40 years coupled
with 0-1 aberrantly-methylated gene, 40-55 years coupled with 0-1 aberrantly
methylated gene; (n=72) (p<0.01). Conclusions: Ultimately, high-risk cirrhosis
patients with 55-over years or 2-3 aberrantly-methylated genes should be paid
more attention to be regularly screened with HCC development.
PMID- 29937941
TI - Multiple Myeloma Index for Risk of Infection.
AB - Based on our earlier research into the main characteristics and risk factors for
infections in hospitalized patients with multiple myeloma, we created the
numerical Multiple Myeloma Index for Risk of Infection (MMIRI) to predict
infection in myeloma patients. The included factors that could influence the
pathogenesis and incidence of infections were sex, performance status, Durie
Salmon stage of disease, International Staging System, serum creatinine level,
immune paresis, neutropenia, serum ferritin level, the presence of any catheters,
disease duration, stable/progressive disease, and type of therapy. For each of
these parameters, the strength of association with infection was statistically
estimated and specific number of points was assigned to each of these parameters,
proportional to the strength of the association. When designing the MMIRI, we
included only those parameters that we determined were pathophysiologically
associated with the infection. After further statistical analysis, we identified
an optimal cutoff score of 6 or above as indicating a significant risk for
infection, with a sensitivity of 93.2% and specificity of 80.2%. The scoring
system in the retrospective receiver operating characteristic analysis showed an
area under the curve of 0.918. The potential value of the MMIRI is the
possibility of identifying those patients who would benefit from the prophylactic
administration of antibiotics and other anti-infective measures while minimizing
the contribution to antibiotic resistance related to the overuse of these drugs.
As far as we know, this index represents the first attempt to create such an
instrument for predicting the occurrence of infections in myeloma patients.
PMID- 29937942
TI - Salvage Carbon Ion Radiation Therapy for Locally Recurrent or Radiation-Induced
Second Primary Sarcoma of the Head and Neck.
AB - Purpose: Salvage radiation therapy (RT) is a potentially curative treatment
option for head and neck sarcomas (HNS) that did not respond to previous
treatment(s). We report the first clinical experience of carbon ion radiotherapy
(CIRT) for salvage treatment of locally recurrent (LR) or RT-induced secondary
HNS after surgery and/or radiotherapy. Methods and Materials: A retrospective
analysis of the ongoing prospective data registries from the Shanghai Proton and
Heavy Ion Center was conducted. Patients with LR-HNS who underwent surgery and/or
RT and those with RT-induced second primary HNS were included. Acute and late
toxicities were evaluated using the Common Terminology Criteria for Adverse
Events version 4.0 and the Radiation Therapy Oncology Group late radiation
toxicity scoring system, respectively. The actuarial 12-month local progression
free and overall survival rates (LPFS and OS) were calculated using the Kaplan
Meier method. Results: Between 10/2015 and 7/2017, 19 consecutive and non
selected patients with LR-HNS or RT-induced secondary HNS received definitive
doses of CIRT delivered with pencil beam scanning technology for salvage. Six
patients had locally recurrent soft-tissue sarcoma, and another 6 had
chondrosarcoma. Among these 12 patients, 4 had received one prior course of RT.
Seven additional patients had an RT-induced second primary soft tissue sarcoma
(STS)/osteosarcoma after RT. The median time between the completion of initial
treatment (either surgery only or surgery followed by adjuvant RT) and salvage
CIRT was 30.6 months. The median follow-up time was 13.1 (range 1.6-41.1) months.
All patients except one (for re-irradiation) completed the planned CIRT for
salvage. The median dose of salvage CIRT was 60 GyE. Three patients developed
local progression, and another 3 developed distant metastasis after salvage CIRT.
Deaths occurred (3 patients) only in patients with radiation-induced second
primary sarcoma at the time of analysis. The actuarial 12-month LPFS, DMFS and OS
rates were 74.6%, 82.6% and 86.5%, respectively. Two patients irradiated for a
second primary sarcoma had Grade 4 bleeding during CIRT, including one who
experienced the rupture of an optic artery aneurysm unrelated to his disease or
the salvage treatment. No patient had Grade 5 toxicity during treatment. Except
for one patient who died of hemorrhage 3.5 months after the completion of CIRT,
no moderate or severe late toxicities were observed. Conclusions: With few
observed acute and late toxicities, salvage CIRT can provide effective short-term
tumor control. Further research, preferably in a prospective fashion, will be
required to confirm the efficacy and safety of salvage CIRT in this patient
population.
PMID- 29937943
TI - PD-L1 Expression On tumor Cells Was Associated With Unfavorable Prognosis In
Esophageal Squamous Cell Carcinoma.
AB - Background: Evidence about the association between programmed cell death ligand 1
(PD-L1) expression and prognosis of esophageal squamous cell carcinoma (ESCC)
were limited and controversial. Thus, the present study aims to investigate the
prognostic value of tumor immune microenvironment (TIM) based on PD-L1 expression
and CD8+ T cell infiltration in ESCC tissues. Methods: From September 2008 to
March 2010, a total of 146 ESCC patients received radical esophagectomy were
retrospectively analyzed in our present study. PD-L1 expression and CD8+ T cell
infiltration were evaluated through immunohistochemistry. The clinicopathological
characteristics and survival were analyzed. Results: There were 111 male and 35
female. The median age was 59.1 years (37-78 years). The positive rate of PD-L1
expression was 61.7%. The rate of high CD8+ T cell infiltration was 33%. No
significant differences were found between clinicopathological features and PD-L1
expression or CD8+ T cell infiltration. PD-L1 expression was significantly
associated with poor overall survival (P=0.010). However, CD8+ T cell
infiltration was not a prognostic risk factor. Type of TIM was significantly
associated with the prognosis of ESCC patients (P=0.021). Conclusions: PD-L1
expression was an independent risk factor for the prognosis of ESCC patients.
Immunotherapy may achieve promising outcomes in ESCC patients with type I TIM.
PMID- 29937944
TI - Cooperative Surface-Particle Catalysis: The Role of the "Active Doughnut" in
Catalytic Oxidation.
AB - We consider the factors that govern the activity of bifunctional catalysts
comprised of active particles supported on active surfaces. Such catalysts are
interesting because the adsorption and diffusion steps, which are often
discounted in "conventional" catalytic scenarios, play a key role here. We
present an intuitive model, the so-called "active doughnut" concept, defining an
active catalytic region around the supported particles. This simple model
explains the role of adsorption and diffusion steps in cascade catalytic cycles
for active particles supported on active surfaces. The concept has two important
practical implications. First, the reaction rate is no longer proportional to the
number of active sites, but rather to the number of "communicative" active sites
those available to the reaction intermediates during their respective lifetimes.
Second, it generates an important testable prediction concerning the dependence
of the total reaction rate on the particle size. With these tools at hand, we
examine six experimental examples of catalytic oxidation from the literature, and
show that the active doughnut concept gives valuable insight even when detailed
mechanistic information is hard to come by.
PMID- 29937945
TI - Social Policy and Cognitive Enhancement: Lessons from Chess.
AB - Should the development of pharmacological cognitive enhancers raise worries about
doping in cognitively demanding activities? In this paper, we argue against using
current evidence relating to enhancement to justify a ban on cognitive enhancers
using the example of chess. It is a mistake to assume that enhanced cognitive
functioning on psychometric testing is transferable to chess performance because
cognitive expertise is highly complex and in large part not merely a function of
the sum specific sub-processes. A deeper reason to doubt that pharmacological
cognitive enhancers would be as significant in mind sports is the misleading
parallel with physical enhancement. We will make the case that cognitive
performance is less mechanical in nature than physical performance. We draw
lessons from this case example of chess for the regulation of cognitive
enhancement more generally in education and the professions. Premature regulation
runs the risk of creating a detrimental culture of suspicion that ascribes
unwarranted blame.
PMID- 29937947
TI - Higher and Lower Pleasures Revisited: Evidence from Neuroscience.
AB - This paper discusses J.S. Mill's distinction between higher and lower pleasures,
and suggests that recent neuroscientific evidence counts against it.
PMID- 29937948
TI - Is the Personal Identity Debate a "Threat" to Neurosurgical Patients? A Reply to
Muller et al.
AB - In their article in this journal, Sabine Muller, Merlin Bittlinger, and Henrik
Walter launch a sweeping attack against what they call the "personal identity
debate" as it relates to patients treated with deep brain stimulation (DBS). In
this critique offered by Muller et al., the personal identity debate is said to:
(a) be metaphysical in a problematic way, (b) constitute a threat to patients,
and (c) use "vague" and "contradictory" statements from patients and their
families as direct evidence for metaphysical theories. In this response, I
critically evaluate Muller et al.'s argument, with a special focus on these three
just-mentioned aspects of their discussion. My conclusion is that Muller et al.'s
overall argument is problematic. It overgeneralizes criticisms that may apply to
some, but certainly not to all, contributions to what they call the personal
identity-debate. Moreover, it rests on a problematic conception of what much of
this debate is about. Nor is Muller et al.'s overall argument fair in its
assessment of the methodology used by most participants in the debate. For these
reasons, we should be skeptical of Muller et al.'s claim that the "personal
identity debate" is a "threat to neurosurgical patients".
PMID- 29937949
TI - Focus on carbon-neutral energy science and technology.
PMID- 29937946
TI - Ethics of Deep Brain Stimulation in Adolescent Patients with Refractory Tourette
Syndrome: a Systematic Review and Two Case Discussions.
AB - Introduction: Tourette Syndrome (TS) is a childhood onset disorder characterized
by vocal and motor tics and often remits spontaneously during adolescence. For
treatment refractory patients, Deep Brain Stimulation (DBS) may be considered.
Methods and Results: We discuss ethical problems encountered in two adolescent TS
patients treated with DBS and systematically review the literature on the topic.
Following surgery one patient experienced side effects without sufficient
therapeutic effects and the stimulator was turned off. After a second series of
behavioural treatment, he experienced a tic reduction of more than 50%. The
second patient went through a period of behavioural disturbances that interfered
with optimal programming, but eventually experienced a 70% tic reduction. Sixteen
DBS surgeries in adolescent TS patients have been reported, none of which pays
attention to ethical aspects. Discussion: Specific ethical issues arise in
adolescent TS patients undergoing DBS relating both to clinical practice as well
as to research. Attention should be paid to selecting patients fairly, thorough
examination and weighing of risks and benefits, protecting the health of children
and adolescents receiving DBS, special issues concerning patient's autonomy, and
the normative impact of quality of life. In research, registration of all TS
cases in a central database covering a range of standardized information will
facilitate further development of DBS for this indication. Conclusion: Clinical
practice should be accompanied by ongoing ethical reflection, preferably covering
not only theoretical thought but providing also insights in the views and
perspectives of those concerned, that is patients, family members and
professionals.
PMID- 29937950
TI - Augmented longitudinal acoustic trap for scalable microparticle enrichment.
AB - We introduce an acoustic microfluidic device architecture that locally augments
the pressure field for separation and enrichment of targeted microparticles in a
longitudinal acoustic trap. Pairs of pillar arrays comprise "pseudo walls" that
are oriented perpendicular to the inflow direction. Though sample flow is
unimpeded, pillar arrays support half-wave resonances that correspond to the
array gap width. Positive acoustic contrast particles of supracritical diameter
focus to nodal locations of the acoustic field and are held against drag from the
bulk fluid motion. Thus, the longitudinal standing bulk acoustic wave (LSBAW)
device achieves size-selective and material-specific separation and enrichment of
microparticles from a continuous sample flow. A finite element analysis model is
used to predict eigenfrequencies of LSBAW architectures with two pillar
geometries, slanted and lamellar. Corresponding pressure fields are used to
identify longitudinal resonances that are suitable for microparticle enrichment.
Optimal operating conditions exhibit maxima in the ratio of acoustic energy
density in the LSBAW trap to that in inlet and outlet regions of the
microchannel. Model results guide fabrication and experimental evaluation of
realized LSBAW assemblies regarding enrichment capability. We demonstrate
separation and isolation of 20 MUm polystyrene and ~10 MUm antibody-decorated
glass beads within both pillar geometries. The results also establish several
practical attributes of our approach. The LSBAW device is inherently scalable and
enables continuous enrichment at a prescribed location. These features benefit
separations applications while also allowing concurrent observation and analysis
of trap contents.
PMID- 29937951
TI - Manipulation of micro-objects using acoustically oscillating bubbles based on the
gas permeability of PDMS.
AB - This paper presents a novel manipulation method for micro-objects using
acoustically oscillating bubbles with a controllable position based on the gas
permeability of polydimethylsiloxane. The oscillating bubble trapped within the
side channel attracts the neighboring micro-objects, and the position of the air
liquid interface is controlled by generating temporary pressure difference
between the side channel and the air channel. To demonstrate the feasibility of
the method in technological applications, polystyrene microparticles of 10 MUm in
diameter were successfully captured, transported, and released. The influence of
pressure difference on the movement speed of the air-liquid interface was
demonstrated in our experiments, and the manipulation performance was also
characterized by varying the frequency of the acoustic excitation and the
pressure difference. Since the bubble generation and the air-liquid interface
movement in our manipulation method do not need any electrochemical reaction and
any high temperature, this on-chip manipulation method provides a controllable,
efficient, and noninvasive tool for handling micro-objects such as particles,
cells, and other entities. The whole manipulation process, including capturing,
transporting, and releasing of particles, spent less than 1 min. It can be used
to select the cells and particles in the microfluidic device or change the cell
culture medium.
PMID- 29937952
TI - Statistics for real-time deformability cytometry: Clustering, dimensionality
reduction, and significance testing.
AB - Real-time deformability (RT-DC) is a method for high-throughput mechanical and
morphological phenotyping of cells in suspension. While analysis rates exceeding
1000 cells per second allow for a label-free characterization of complex
biological samples, e.g., whole blood, data evaluation has so far been limited to
a few geometrical and material parameters such as cell size, deformation, and
elastic Young's modulus. But as a microscopy-based technology, RT-DC actually
generates and yields multidimensional datasets that require automated and
unbiased tools to obtain morphological and rheological cell information. Here, we
present a statistical framework to shed light on this complex parameter space and
to extract quantitative results under various experimental conditions. As model
systems, we apply cell lines as well as primary cells and highlight more than 11
parameters that can be obtained from RT-DC data. These parameters are used to
identify sub-populations in heterogeneous samples using Gaussian mixture models,
to perform a dimensionality reduction using principal component analysis, and to
quantify the statistical significance applying linear mixed models to datasets of
multiple replicates.
PMID- 29937953
TI - Analysis of adhesion kinetics of cancer cells on inflamed endothelium using a
microfluidic platform.
AB - Metastasis is the ultimate cause of death among the vast majority of cancer
patients. This process is comprised of multiple steps, including the migration of
circulating cancer cells across microvasculature. This trans-endothelial
migration involves the adhesion and eventual penetration of cancer cells to the
vasculature of the target organ. Many of these mechanisms remain poorly
understood due to poor control of pathophysiological conditions in tumor models.
In this work, a microfluidic device was developed to support the culture and
observation of engineered microvasculature with systematic control of the
environmental characteristics. This device was then used to study the adhesion of
circulating cancer cells to an endothelium under varying conditions to delineate
the effects of hemodynamics and inflammations. The resulting understanding will
help to establish a quantitative and biophysical mechanism of interactions
between cancer cells and endothelium.
PMID- 29937954
TI - Acupuncture and Magnets: Is There a Clinical Role?
PMID- 29937955
TI - Battlefield Acupuncture: My Story.
PMID- 29937956
TI - Acupuncture and Integrative Medicine in Pediatrics.
PMID- 29937958
TI - Abstracts and Commentaries on Key Articles in the Literature.
PMID- 29937957
TI - How Do You Treat Asthma in Your Practice?
PMID- 29937959
TI - The Ninth International Symposium on Auriculotherapy: Building on the Past for
the Future.
PMID- 29937960
TI - Dedication to Dr. Marco Romoli.
PMID- 29937961
TI - A First in Singapore: East Meets West at the 2017 International Auriculotherapy
Symposium.
PMID- 29937962
TI - Neurology, Auriculotherapy, and Medical Education.
PMID- 29937963
TI - Application of Polyvagal Theory to Auricular Acupuncture.
PMID- 29937964
TI - Enchantment and Enhancement in the Land of the Merlion.
PMID- 29937965
TI - Auriculotherapy in Neurology as an Evidence-Based Medicine: A Brief Overview.
AB - This article provides a brief overview of the use of auriculotherapy in the
treatment of various neurologic conditions. This overview is not comprehensive
and is meant to be primarily informative. It is based on the premise that
auricular acupuncture is an evidence-based medicine.
PMID- 29937966
TI - An Analysis of the Development of Auricular Acupuncture in China in the Past 10
Years.
AB - Objective: The aim of this research was to analyze recent developments of
auricular acupuncture in China during the past 10 years, from 2007 to 2016.
Methods: The articles evaluated related to auricular acupuncture studies
published in the last 10 years, from 2007 to 2016. The articles were retrieved
from the China National Knowledge Infrastructure (CNKI) full-text journal
database and from Tsinghua Tongfang, the Chinese Knowledge net. The history of
auricular acupuncture, the overall status of the research, and the current use of
standardization were analyzed and summarized. Results: The literature research of
auricular acupuncture in China revealed that there was a high frequency of
publications over the last 10 years. Conclusions: Development of more auricular
acupuncture research teams, improvement of the level and quality of the research,
and basic and clinical research investigations on auricular acupuncture in China
have demonstrated continuous improvement in the past 10 years. It is hoped that
this research will continue into the future, offering greater contributions to
the development of auricular acupuncture for the health care of human beings.
PMID- 29937967
TI - Auricular Medicine in Neonatal Care.
AB - This article explores the possibilities of applying ear acupuncture to newborn
infants. In addition to the use of needle acupuncture, there are also noninvasive
applications that are preferred for patients in this particular age group. Based
on the limited literature, ear acupuncture could be an effective nonpharmacologic
approach for the treatment of pain in newborn infants and for addressing symptoms
of neonatal abstinence syndrome. However, studies on safety, side-effects, and
other indications are still lacking.
PMID- 29937969
TI - Auricular Chromotherapy in the Treatment of Psychologic Trauma, Phobias, and
Panic Disorder.
AB - Auricular chromotherapy has shown promising results in the treatment of
psychologic trauma and anxiety disorders, such as phobias and panic attacks. With
its relatively easy and quick technical application, this procedure could be an
indispensable tool for physicians. However, its mechanism of action is not yet
understood completely. Objective: To treat patients suffering from trauma,
phobia, and panic attack with auricular chromotherapy. Materials and Methods: The
protocol was applied in 160 patients (135 who experienced traumas; 15 patients
with specific phobias and 10 patients with panic disorder). They are 134 women,
26 men, ages 20-60. Results: The treatment showed 93% of positive response.
Conclusion: This procedure shows the possibility of drawing a path from the
external ear to traumatic memories, anxiety disorders and phobias.
PMID- 29937970
TI - Active Ear Acupuncture Points in Neonates: Initial Results in a New Research
Field.
AB - Background: Little is known about active ear acupuncture points (EAP) in
neonates. Previous unblinded studies by Stahler van Amerongen et al. showed that
neonates have detectable active EAP, and that sick neonates could have more EAP
relative to healthy neonates. EAP was investigated in an unblinded trial
involving neonates with neonatal abstinence syndrome (NAS). Furthermore, a
blinded, controlled observational trial was conducted to compare active EAP
present in healthy neonates with EAP of sick neonates. Materials and Methods: An
electrical point search device (PS3, Silberbauer, Vienna, Austria) was used to
detect EAP. Active EAP were detected with an integrated optical and acoustical
signal, and readings were transferred to a standardized ear map. A Mann-Whitney-U
test and Spearman's correlation were used for statistical analysis. Results: A
total of 94 neonates were enrolled across both trials. EAP were detectable in all
healthy and sick neonates. In the blinded trial, sick neonates had a
significantly higher number of active EAP than did healthy neonates. Conclusions:
A notable difference in the number of active EAP was detected between healthy and
sick neonates. More trials with larger sample sizes are needed to confirm the
diagnostic power of EAP in neonates.
PMID- 29937968
TI - Anatomo-Physiologic Basis for Auricular Stimulation.
AB - Introduction: Stimulation of cranial nerves modulates central nervous system
(CNS) activity via the extensive connections of their brainstem nuclei to higher
order structures. Clinical experience with vagus-nerve stimulation (VNS)
demonstrates that it produces robust therapeutic effects, however, posing
concerns related to its invasiveness and side-effects. Discussion: Trigeminal
nerve stimulation (TNS) has been recently proposed as a valid alternative to VNS.
The ear presents afferent vagus and trigeminal-nerve distribution; its
innervation is the theoretical basis of different reflex therapies, including
auriculotherapy. An increasing number of studies have shown that several
therapeutic effects induced by invasive VNS and TNS, can be reproduced by
noninvasive auricular-nerve stimulation. However, the sites and neurobiologic
mechanisms by which VNS and TNS produce their therapeutic effects are not clear
yet. Conclusions: Accumulating evidence suggests that VNS and TNS share multiple
levels and mechanisms of action in the CNS.
PMID- 29937971
TI - Painless Laser Acupuncture for Smoking Cessation.
AB - Objective: Traditional Chinese Medicine (TCM) in healthcare is based on the
holistic concept of smooth energy flow. The energy helps maintain the circulation
of Blood and bodily processes. An efficient supply of consistent energy and good
circulation helps support the body's homeostasis. In therapeutics, low-level
laser energy can be transferred to the body (via the auricle) to activate or
maintain homeostasis through specifically appropriate auricular sites. The goal
of this research was to track the effects of painless laser acupuncture (PLA) on
a group of highly motivated patients who wanted to quit smoking. Materials and
Methods: Executives in their early 30s-50s, who were highly motivated and
stressed individuals were treated. Most of these 175 patients smoked 1 pack of
cigarettes per day (20 cigarettes), with a few patients smoking more than 1 pack
per day. The treatment consisted of PLA applied to both auricular and body
acupuncture points in a total of 7 sessions. Results: There was general
satisfaction among the patients about the treatment. Of 24 females (13.72%), 21
(87.50%) did not smoke after completing the 7 sessions. Two women reported that
despite not having real cravings to smoke, they smoked 1-2 cigarettes per day.
One woman (4.12%) reported that she smoked 2-3 cigarettes. Conclusions: The PLA
technique for smoking cessation, combined with the principles of TCM, not only
helps smokers stop smoking but also restores their homeostasis and good health.
By selecting the optimal auricular and body acupuncture points and meridian
channels and applying laser energy dosages, the homeostatic hence healing process
can be synergized.
PMID- 29937972
TI - Nonrotating Convective Self-Aggregation in a Limited Area AGCM.
AB - We present nonrotating simulations with the Goddard Earth Observing System (GEOS)
atmospheric general circulation model (AGCM) in a square limited area domain over
uniform sea surface temperature. As in previous studies, convection spontaneously
aggregates into humid clusters, driven by a combination of radiative and moisture
convective feedbacks. The aggregation is qualitatively independent of resolution,
with horizontal grid spacing from 3 to 110 km, with both explicit and
parameterized deep convection. A budget for the spatial variance of column moist
static energy suggests that longwave radiative and surface flux feedbacks help
establish aggregation, while the shortwave feedback contributes to its
maintenance. Mechanism-denial experiments confirm that aggregation does not occur
without interactive longwave radiation. Ice cloud radiative effects help support
the humid convecting regions but are not essential for aggregation, while liquid
clouds have a negligible effect. Removing the dependence of parameterized
convection on tropospheric humidity reduces the intensity of aggregation but does
not prevent the formation of dry regions. In domain sizes less than (5,000 km)2,
the aggregation forms a single cluster, while larger domains develop multiple
clusters. Larger domains initialized with a single large cluster are unable to
maintain them, suggesting an upper size limit. Surface wind speed increases with
domain size, implying that maintenance of the boundary layer winds may limit
cluster size. As cluster size increases, large boundary layer temperature
anomalies develop to maintain the surface pressure gradient, leading to an
increase in the depth of parameterized convective heating and an increase in
gross moist stability.
PMID- 29937973
TI - Monthly ENSO Forecast Skill and Lagged Ensemble Size.
AB - The mean square error (MSE) of a lagged ensemble of monthly forecasts of the Nino
3.4 index from the Climate Forecast System (CFSv2) is examined with respect to
ensemble size and configuration. Although the real-time forecast is initialized 4
times per day, it is possible to infer the MSE for arbitrary initialization
frequency and for burst ensembles by fitting error covariances to a parametric
model and then extrapolating to arbitrary ensemble size and initialization
frequency. Applying this method to real-time forecasts, we find that the MSE
consistently reaches a minimum for a lagged ensemble size between one and eight
days, when four initializations per day are included. This ensemble size is
consistent with the 8-10 day lagged ensemble configuration used operationally.
Interestingly, the skill of both ensemble configurations is close to the
estimated skill of the infinite ensemble. The skill of the weighted, lagged, and
burst ensembles are found to be comparable. Certain unphysical features of the
estimated error growth were tracked down to problems with the climatology and
data discontinuities.
PMID- 29937974
TI - Current Innovations in Medicinal Chemistry and Chemical Biology.
PMID- 29937975
TI - Expansion of cat-ELCCA for the Discovery of Small Molecule Inhibitors of the Pre
let-7-Lin28 RNA-Protein Interaction.
AB - Dysregulation of microRNA (miRNA) expression has been linked to many human
diseases; however, because of the challenges associated with RNA-targeted drug
discovery, additional approaches are needed for probing miRNA biology. The
emerging regulatory role of miRNA-binding proteins in miRNA maturation presents
such an alternative strategy. Exploiting our laboratory's click chemistry-based
high-throughput screening (HTS) technology, catalytic enzyme-linked click
chemistry assay or cat-ELCCA, we have designed a modular method by which to
discover new chemical tools for manipulating pre-miRNA-miRNA-binding protein
interactions. Using the pre-let-7d-Lin28 interaction as proof-of-concept, the
results presented demonstrate how HTS using cat-ELCCA can enable the discovery of
small molecules targeting RNA-protein interactions.
PMID- 29937976
TI - Why Decreasing Lipophilicity Alone Is Often Not a Reliable Strategy for Extending
IV Half-life.
AB - The optimization of the pharmacokinetic profile of a drug is one of the crucial
aspects of medicinal chemistry campaigns. When efficacy is driven by a continuous
coverage of the minimum efficacious plasma concentration, half-life must be
optimized to achieve the optimal pharmacokinetic profile. The consensus in the
field is that decreasing clearance, as opposed to increasing volume of
distribution, is a better strategy to prolong half-life. While both the
pharmacokinetic theory and the need for an optimal safety profile support this
approach, this needs to be integrated with practical indications concerning the
strategy to optimize clearance. This work presents an extensive analysis of
Genentech's in vitro and in vivo rat pharmacokinetic data, which highlights how
half-life optimization through simple modulation of lipophilicity is generally
not a successful strategy. Decreasing lipophilicity without addressing a
metabolic soft-spot will often lead to both lower clearance and lower volume of
distribution without extending half-life.
PMID- 29937977
TI - Strategy for Extending Half-life in Drug Design and Its Significance.
AB - Preclinical optimization of compounds toward viable drug candidates requires an
integrated understanding of properties that impact predictions of the clinically
efficacious dose. The importance of optimizing half-life, unbound clearance, and
potency and how they impact dose predictions are discussed in this letter. Modest
half-life improvements for short half-life compounds can dramatically lower the
efficacious dose. The relationship between dose and half-life is nonlinear when
unbound clearance is kept constant, whereas the relationship between dose and
unbound clearance is linear when half-life is kept constant. Due to this
difference, we show that dose is more sensitive to changes in half-life than
changes in unbound clearance when half-lives are shorter than 2 h. Through
matched molecular pair analyses, we also show that the strategic introduction of
halogens is likely to increase half-life and lower projected human dose even
though increased lipophilicity does not guarantee extended half-life.
PMID- 29937978
TI - Synthesis of Thymoquinone-Artemisinin Hybrids: New Potent Antileukemia,
Antiviral, and Antimalarial Agents.
AB - A series of hybrid compounds based on the natural products artemisinin and
thymoquinone was synthesized and investigated for their biological activity
against the malaria parasite Plasmodium falciparum 3D7 strain, human
cytomegalovirus (HCMV), and two leukemia cell lines (drug-sensitive CCRF-CEM and
multidrug-resistant subline CEM/ADR5000). An unprecedented one-pot method of
selective formation of C-10alpha-acetate 14 starting from a 1:1 mixture of C
10alpha- to C-10beta-dihydroartemisinin was developed. The key step of this
facile method is a mild decarboxylative activation of malonic acid mediated by
DCC/DMAP. Ether-linked thymoquinone-artemisinin hybrids 6a/b stood out as the
most active compounds in all categories, while showing no toxic side effects
toward healthy human foreskin fibroblasts and thus being selective. They
exhibited EC50 values of 0.2 MUM against the doxorubicin-sensitive as well as the
multidrug-resistant leukemia cells and therefore can be regarded as superior to
doxorubicin. Moreover, they showed to be five times more active than the standard
drug ganciclovir and nearly eight times more active than artesunic acid against
HCMV. In addition, hybrids 6a/b possessed excellent antimalarial activity (EC50 =
5.9/3.7 nM), which was better than that of artesunic acid (EC50 = 8.2 nM) and
chloroquine (EC50 = 9.8 nM). Overall, most of the presented thymoquinone
artemisinin-based hybrids exhibit an excellent and broad variety of biological
activities (anticancer, antimalarial, and antiviral) combined with a low
toxicity/high selectivity profile.
PMID- 29937979
TI - Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of
CDK8.
AB - Cortistatin A is a natural product isolated from the marine sponge Corticium
simplex and was found to be a potent and selective inhibitor of CDK8. Many
synthetic groups have reported total syntheses of Cortistatin A; however, these
syntheses require between 16 and 30 steps and report between 0.012-2% overall
yields, which is not amenable to large-scale production. Owing to similarities
between the complex core of Cortistatin A and the simple steroid core, we
initiated a campaign to design simple, more easily prepared CDK8 inhibitors based
on a steroid scaffold that would be more convenient for large-scale synthesis.
Herein, we report the discovery and optimization of JH-VIII-49, a potent and
selective inhibitor of CDK8 with a simple steroid core that has an eight-step
synthesis with a 33% overall yield, making it suitable for large-scale
preparation. Using this scaffold, we then developed a bivalent small molecule
degrader, JH-XI-10-02, that can recruit the E3 ligase CRL4Cereblon to promote the
ubiquitination and proteosomal degradation of CDK8.
PMID- 29937981
TI - Riluzole-Triazole Hybrids as Novel Chemical Probes for Neuroprotection in
Amyotrophic Lateral Sclerosis.
AB - Despite intense attention from biomedical and chemical researchers, there are few
approved treatments for amyotrophic lateral sclerosis (ALS), with only riluzole
(Rilutek) and edaravone (Radicava) currently available to patients. Moreover, the
mechanistic basis of the activity of these drugs is currently not well-defined,
limiting the ability to design new medicines for ALS. This Letter describes the
synthesis of triazole-containing riluzole analogues, and their testing in a novel
neuroprotective assay. Seven compounds were identified as having neuroprotective
activity, with two compounds having similar activity to riluzole.
PMID- 29937980
TI - Homogeneous Assay for Target Engagement Utilizing Bioluminescent Thermal Shift.
AB - Protein thermal shift assays (TSAs) provide a means for characterizing target
engagement through ligand-induced thermal stabilization. Although these assays
are widely utilized for screening libraries and validating hits in drug discovery
programs, they can impose encumbering operational requirements, such as the
availability of purified proteins or selective antibodies. Appending the target
protein with a small luciferase (NanoLuc) allows coupling of thermal denaturation
with luminescent output, providing a rapid and sensitive means for assessing
target engagement in compositionally complex environments such as permeabilized
cells. The intrinsic thermal stability of NanoLuc is greater than mammalian
proteins, and our results indicate that the appended luciferase does not alter
thermal denaturation of the target protein. We have successfully applied the
NanoLuc luciferase thermal shift assay (NaLTSA) to several clinically relevant
protein families, including kinases, bromodomains, and histone deacetylases. We
have also demonstrated the suitability of this assay method for library screening
and compound profiling.
PMID- 29937982
TI - Chemical Proteomic Characterization of a Covalent KRASG12C Inhibitor.
AB - The KRASG12C protein product is an attractive, yet challenging, target for small
molecule inhibition. One option for therapeutic intervention is to design small
molecule ligands capable of binding to and inactivating KRASG12C via formation of
a covalent bond to the sulfhydryl group of cysteine 12. In order to better
understand the cellular off-target interactions of Compound 1, a covalent
KRASG12C inhibitor, we have completed a series of complementary chemical
proteomics experiments in H358 cells. A new thiol reactive probe (TRP) was
designed and used to construct a cellular target occupancy assay for KRASG12C. In
addition, the thiol reactive probes allowed us to profile potential off-target
interactions of Compound 1 with over 3200 cysteine residues. In order to
complement the TRP data we designed Compound 2, an alkyne containing version of
Compound 1, to serve as bait in competitive chemical proteomics experiments.
Herein, we describe and compare data from both the TRP and the click chemistry
probe pull down experiments.
PMID- 29937983
TI - Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed
by Activity-Based Protein Profiling.
AB - Wnt proteins are secreted morphogens that play critical roles in embryonic
development and tissue remodeling in adult organisms. Aberrant Wnt signaling
contributes to diseases such as cancer. Wnts are modified by an unusual O-fatty
acylation event (O-linked palmitoleoylation of a conserved serine) that is
required for binding to Frizzled receptors. O-Palmitoleoylation of Wnts is
introduced by the porcupine (PORCN) acyltransferase and removed by the serine
hydrolase NOTUM. PORCN inhibitors are under development for oncology, while NOTUM
inhibitors have potential for treating degenerative diseases. Here, we describe
the use of activity-based protein profiling (ABPP) to discover and advance a
class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively
inhibit NOTUM. An optimized NHH carbamate inhibitor, ABC99, preserves Wnt
mediated cell signaling in the presence of NOTUM and was also converted into an
ABPP probe for visualizing NOTUM in native biological systems.
PMID- 29937984
TI - Azithromycin-Induced Changes to Bacterial Membrane Properties Monitored in Vitro
by Second-Harmonic Light Scattering.
AB - We present a nonlinear light scattering method for monitoring, with real-time
resolution and membrane specificity, changes in molecular adsorption, and
transport at bacterial membranes induced by an antimicrobial compound.
Specifically, time-resolved second-harmonic light scattering (SHS) is used to
quantify azithromycin-induced changes to bacterial membrane permeability in
colloidal suspensions of living Escherichia coli. Variations in membrane
properties are monitored through changes in the adsorption and transport rates of
malachite green, a hydrophobic cation that gives SHS signal. Regardless of
concentration, instantaneous treatment with azithromycin showed no significant
changes in membrane permeability. However, 1 h pretreatment with subminimum
inhibitory concentrations of azithromycin induced an order-of-magnitude
enhancement in the permeability of both the outer membrane and, through
facilitation of a new transport mechanism, the cytoplasmic membrane of the
bacteria as well. This study illustrates SHS as a novel tool for monitoring
antimicrobial-induced changes to membrane properties in living bacteria.
PMID- 29937985
TI - Intraoperative radiation therapy as part of planned monotherapy for early-stage
breast cancer.
AB - Introduction: Adjuvant whole breast radiation therapy has developed into the
standard of care for patients following a lumpectomy for early-stage breast
cancer. However, there is recent interest in intraoperative radiation therapy
(IORT) to minimize toxicity while still improving local control beyond surgical
resection and anti-estrogen therapy alone. Materials and methods: All patients
were evaluated pre-operatively in a multidisciplinary clinic setting at a
community hospital for suitability for breast conservation therapy. A total of
109 patients were reviewed receiving 110 IORT treatments. Patients were followed
with clinical breast examinations and mammography as clinically indicated.
Results: At a median follow-up of 29.9 months, 2/110 (1.8%) patients experienced
a local failure. One patient (0.9%) experienced a regional failure. Local
control, disease-free survival and overall survival at 3 years were 98.9% (95%CI
92.2-99.8), 97.2% (95%CI 88.9-99.3), and 96.0% (95%CI 84.9-99.0), respectively.
Five-year local control, disease-free survival, and overall survival rates were
96.3% (95%CI 84.7-99.2), 94.6% (95%CI 83.2-98.3), and 92.5% (95%CI 80.4-97.3),
respectively. Patient self-reported cosmetic outcome was available for 51
patients, with all patients reporting being either very pleased, pleased, or
satisfied with their cosmetic outcome, and no patients reported being
dissatisfied or worse. Conclusions: The results of our series suggest the
feasibility of utilizing IORT in a community-based cancer center with a high
degree of local control, and patient satisfaction with regard to cosmesis. While
the results of this series suggest that IORT may be a promising modality, longer
follow-up is warranted to better understand exactly which clinicopathological
features can predict long-term locoregional disease control.
PMID- 29937986
TI - Effect of BioZorb(r) surgical marker placement on post-operative radiation boost
target volume.
AB - Objective: BioZorb(r) is a tumor bed marker placed during partial mastectomy for
targeted post-operative radiation. This study was designed to evaluate BioZorb(r)
effect on radiation boost clinical target volume (CTV), planning target volume
(PTV), median dose to ipsilateral lung (Gy), and heart irradiation in left-sided
cancers. Methods: Data was collected via a retrospective cohort study with two
study arms: BioZorb(r) intra-operative placement versus no BioZorb(r) placement.
Patients were stratified by BMI, age, tumor laterality and volume, and cancer
stage. Mean, standard deviation, median, range of cubic centimeters of clinical
and planning target volume, cardiac dose in left-sided cancers, ipsilateral lung
dose, and volume of ipsilateral lung receiving 20 Gy were reported. Results: Of
143 patients, median CTV (cm3) was 8.7 and 14.2 (P = 0.0048), median PTV (cm3)
was 53.2 and 79.6 (P = 0.0010), median ipsilateral lung Gy was 7.53 and 6.74 (P =
0.0099) and volume (cc) of ipsilateral radiation lung at 20 Gy was 13.4 and 12 (P
= 0.008), and median heart Gy in left-sided cancers was 2.01 and 2.21 (P =
0.9952) in BioZorb(r) and non-BioZorb(r) arms, respectively. Patients with BMIs
of 25-30 had CTV medians of 7.8 and 11.1 in BioZorb(r) and non-BioZorb(r) arms,
respectively (P = 0.0293). Conclusion: The BioZorb(r) arm showed statistically
significant reductions in CTV and PTV but not ipsilateral lung or heart
irradiation.
PMID- 29937987
TI - XIAP at the crossroads of cell death and inflammation.
PMID- 29937988
TI - Genetic polymorphisms in ataxin-3 and liver cirrhosis risk related to aflatoxin
B1.
AB - Background: Altered expression of ataxin-3 (AT3) can modify DNA repair capacity
and is observed in human diseases. The genetic polymorphisms of this gene in
aflatoxin B1 (AFB1)-related liver cirrhosis (LC) have not yet been elucidated.
Materials and Methods: We conducted a hospital-based case-control study,
including 384 patients with LC and 851 controls without any liver diseases, to
assess the association between 264 polymorphisms in AT3 and AFB1-related LC risk.
Genotype were tested using TaqMan-PCR or sequencing technique. Results: We found
three differentially distributed SNPs (rs8021276, rs7158733, and rs10146249) via
the screening analysis; however, only rs8021276 polymorphism was further
identified to modify the risk of LC. Compared with the homozygote of rs8021276 A
alleles (rs8021276-AA), the genotypes of rs8021276 G alleles (rs8021276-AG or
GG) increased LC risk (OR: 2.48 and 6.98; 95% CI: 1.84-3.33 and 4.35-11.22,
respectively). Significant interactive effects between risk genotypes and AFB1
exposure status were also observed in the joint effects analysis. Additionally,
rs8021276 polymorphism was also associated with down-regulation of AT3 mRNA
expression and increasing AFB1-DNA adducts in liver tissues with cirrhosis.
Conclusions: These results suggest AT3 polymorphisms may be risk biomarkers of
AFB1-related LC, and rs8021276 is a potential candidate.
PMID- 29937989
TI - A pilot study of circulating microRNAs as potential biomarkers of Fabry disease.
AB - Patients suffering from Fabry disease (FD), a lysosomal storage disorder, show a
broad range of symptoms and the diagnosis followed by the therapeutic decision
remains a great challenge. The biomarkers available today have not proven to be
useful for predicting the evolution of the disease and for assessing response to
therapy in many patients. Here, we used high-throughput microRNA profiling
methodology to identify a specific circulating microRNA profile in FD patients.
We discovered a pattern of 10 microRNAs able to identify FD patients when
compared to healthy controls. Notably, two of these: the miR199a-5p and the miR
126-3p are able to discriminate FDs from the control subjects with left
ventricular hypertrophy, a frequent but non-specific FD symptom. These same
microRNAs are also sensitive to enzyme replacement therapy showing variation in
the subjects under treatment. Furthermore, two other microRNAs of the profile,
the miR-423-5p and the miR-451a, seem useful to highlight cardiac involvement in
FD patients. A literature and database search revealed that miR-199a-5p, miR-126
3p, miR-423-5p and miR-451a are known to be linked to pathological states that
occur during the FD development. In particular, miR-199a-5p, and miR-126-3p are
involved in endothelial dysfunction and miR-423-5p and miR-451a in myocardial
remodeling. In conclusion, in this study we identified a common plasma microRNA
profile in FD patients, useful not only for the correct classification of Fabry
patients regardless of sex and age, but also to evaluate the response to therapy.
Furthermore, our observations suggest that some microRNAs of this profile
demonstrate prognostic qualities.
PMID- 29937990
TI - Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors.
AB - Lung cancer is the main cancer killer in both men and women, mostly due to the
rapid development of drug resistant metastatic disease. Here, we evaluate the
potential involvement of SRC family kinases (SFK) in lung cancer biology and
assess the possible benefits of their inhibition as a therapeutic approach. We
demonstrated that various SRC family members, including LYN and LCK, normally
expressed solely in hematopoietic cells and neural tissues, are overexpressed and
activated in a panel of SCLC and NSCLC cell lines. This was clinically relevant
as LYN and FYN are also overexpressed in lung cancer clinical specimens.
Moreover, LYN overexpression correlated with decreased patient survival on
univariate and multivariate analysis. Dasatinib (BMS-354825), a SRC/ABL
inhibitor, effectively blocked SFK activation at nanomolar concentrations which
correlated with a significant decrease in cell numbers of multiple lung cancer
cell lines. This effect was matched by a decrease in DNA synthesis, but only
moderate induction of apoptosis. Indeed, dasatinib as well as PP2, another SFK
inhibitor, strongly induced autophagy that likely prevented apoptosis. However,
inhibition of this autophagic response induced robust apoptosis and sensitised
lung cancer cells to dasatinib in vitro and in vivo. Our results provide an
explanation for why dasatinib failed in NSCLC clinical trials. Furthermore, our
data suggest that combining SFK inhibitors with autophagy inhibitors could
provide a novel therapeutic approach in this disease.
PMID- 29937991
TI - Identification, characterization and application of a new peptide against
anterior gradient homolog 2 (AGR2).
AB - The cancer-associated protein Anterior Gradient 2 (AGR2) has been described,
predominantly in adenocarcinomas. Increased levels of extracellular AGR2 (eAGR2)
have been correlated with poor prognosis in cancer patients, making it a
potential biomarker. Additionally, neutralizing AGR2 antibodies showed
preclinical effectiveness in murine cancer models suggesting eAGR2 may be a
therapeutic target. We set out to identify a peptide by mRNA display that would
serve as a theranostic tool targeting AGR2. This method enables the selection of
peptides from a complex (>1011) library and incorporates a protease incubation
step that filters the selection for serum stable peptides. We performed six
successive rounds of enrichment using a 10-amino acid mRNA display library and
identified several AGR2 binding peptides. One of these peptides (H10),
demonstrated high affinity binding to AGR2 with a binding constant (KD) of 6.4
nM. We developed an AGR2 ELISA with the H10 peptide as the capture reagent. Our
H10-based ELISA detected eAGR2 from cancer cell spent media with a detection
limit of (20-50 ng/ml). Furthermore, we investigated the therapeutic utility of
H10 and discovered that it inhibited cell viability at IC50 (9-12 MUmoles/L) in
cancer cell lines. We also determined that 10 MUg/ml of H10 was sufficient to
inhibit cancer cell migration in breast and prostate cancer cell lines. A control
peptide did not show any appreciable activity in these cells. The H10 peptide
showed promise as both a novel diagnostic and a potential therapeutic peptide.
PMID- 29937992
TI - Neoadjuvant chemotherapy in breast cancer: a dose-dense schedule in real life and
putative role of PIK3CA mutations.
AB - Background: Dose-dense chemotherapy is one of the treatments of choice for
neoadjuvant therapy in breast cancer (BC). Activating mutations in PIK3CA gene
predict worse response to neoadjuvant chemotherapy for HER2-positive patients,
while their role is less clearly defined for HER2-negative tumors. Methods: We
conducted a phase I/II study of neoadjuvant, sequential, dose-dense
anthracycline/taxane chemotherapy, plus trastuzumab in HER2-positive patients and
investigated the correlation of pre-treatment PIK3CA mutation status with
pathologic complete response (pCR) and long-term outcome in a real-life setting.
Results: we established a dose-dense docetaxel recommended dose of 60 mg/m2 and
65 mg/m2, with or without trastuzumab, respectively, according to HER2-status,
following dose-dense epirubicin-cyclophosphamide (90/600 mg/m2), every 2 weeks.
The overall pCR rate was 21.4%; median disease-free survival (DFS) was 52 months
and median overall survival (OS) was not yet reached. PIK3CA mutation status was
not significantly associated with the pCR rate: 18% for both mutated and wild
type patients. The pCR rate was: 25% in the mutated and 24% in the wild-type (p
0.560) cohort of the HER2-positive subgroup; 33% both in the mutant and wild-type
cohort of the triple-negative subgroup; no pCR neither in the mutant nor in the
wild-type cohort of the HR-positive/HER2-negative subgroup. Among the HER2
positive population, a trend toward worse DFS was observed in case of mutation,
as opposed to the triple negative population. Conclusions: This study proposes an
effective and safe neoadjuvant dose-dense anthracycline/taxane schedule and
suggests that PIK3CA mutation analysis can be usefully performed in real-life
clinical practice.
PMID- 29937993
TI - Cytogenetic damage analysis in mice chronically exposed to low-dose internal
tritium beta-particle radiation.
AB - The aim of this study was to carry out a comprehensive examination of potential
genotoxic effects of low doses of tritium delivered chronically to mice and to
compare these effects to the ones resulting from equivalent doses of gamma
irradiation. Mice were chronically exposed for one or eight months to either
tritiated water (HTO) or organically bound tritium (OBT) in drinking water at
concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal beta
particle resulting from such tritium treatments were calculated and matching
external gamma-exposures were carried out. We measured cytogenetic damage in bone
marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium
doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs,
as well as its relative biological effectiveness (RBE). Neither tritium, nor
gamma exposures produced genotoxic effects in bone marrow. However, significant
increases in chromosome damage rates in PBLs were found as a result of chronic
OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an
external acute gamma-exposure ex vivo, the RBE of OBT for chromosome aberrations
induction was evaluated to be significantly higher than 1 at cumulative tritium
doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the
genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be
higher than currently assumed.
PMID- 29937994
TI - The landscape of somatic mutation in sporadic Chinese colorectal cancer.
AB - Colorectal cancer is the fifth prevalent cancer in China. Nevertheless, a large
scale characterization of Chinese colorectal cancer mutation spectrum has not
been carried out. In this study, we have performed whole exome-sequencing
analysis of 98 patients' tumor samples with matched pairs of normal colon tissues
using Illumina and Complete Genomics high-throughput sequencing platforms.
Canonical CRC somatic gene mutations with high prevalence (>10%) have been
verified, including TP53, APC, KRAS, SMAD4, FBXW7 and PIK3CA. PEG3 is identified
as a novel frequently mutated gene (10.6%). APC and Wnt signaling exhibit
significantly lower mutation frequencies than those in TCGA data. Analysis with
clinical characteristics indicates that APC gene and Wnt signaling display lower
mutation rate in lymph node positive cancer than negative ones, which are not
observed in TCGA data. APC gene and Wnt signaling are considered as the key
molecule and pathway for colorectal cancer initiation, and these findings greatly
undermine their importance in tumor progression for Chinese patients. Taken
together, the application of next-generation sequencing has led to the
determination of novel somatic mutations and alternative disease mechanisms in
colorectal cancer progression, which may be useful for understanding disease
mechanism and personalizing treatment for Chinese patients.
PMID- 29937995
TI - Identifying patients with an unfavorable prognosis in early stages of colorectal
carcinoma.
AB - Background: In recent years, the concept of liquid biopsy diagnostics in
detection and progress monitoring of malignant diseases gained significant
awareness. We here report on a semi-quantitative real-time cytokeratin 20 RT-PCR
based assay, for detecting circulating tumor cells within a fraction of
peripheral blood mononuclear cells in colorectal cancer patients. Methods: In
total, 381 patients were included. Prior to surgical tumor resection, a
peripheral blood sample was drawn. Mononuclear cells were isolated by Ficoll
centrifugation and a cytokeratin 20 qRT-PCR assay was performed. Quantitative PCR
data was assessed regarding histopathological characteristics and patients'
clinical outcome. Results: A cut-off value was determined at >= 2.77 [EU].
Stratifying patients by this cut-off, it represents a statistically highly
significant prognostic marker for both the overall and disease-free survival in
the entire cohort UICC I-IV (both p<0.001) and in early tumor stages UICC I+II
(overall survival p=0.003 and disease-free survival p=0.005). In multivariate
analysis, the cut-off value stands for an independent predictor of significantly
worse overall and disease-free survival (p=0.035 and p=0.047, respectively).
Conclusion: We successfully established a highly sensitive real-time qRT-PCR
assay by which we are able to identify colorectal cancer patients at risk for an
unfavorable prognosis in UICC I and II stages.
PMID- 29937996
TI - Synuclein gamma expression enhances radiation resistance of breast cancer cells.
AB - Resistance to therapy is a major obstacle for the effective treatment of cancer.
Expression of synuclein-gamma (SNCG) has been associated with poor prognosis and
resistance to therapy. While reports on SNCG overexpression contributing to
chemoresistance exist, limited information is available on the relationship
between SNCG and radioresistance of cancer cells. Here we investigated the role
of SNCG in radiation resistance in breast cancer cells. siRNA mediated knockdown
of SNCG (siSNCG) markedly reduced SNCG protein level compared to scrambled siRNA
(siScr) treatment. Furthermore, siSNCG treatment sensitized Estrogen Receptor
positive breast cancer cells (MCF7 and T47D) to ionizing radiation at 4 to 12 Gy
as evidenced by the significant increase of apoptotic or senescent cells and
reduction in clonogenic cell survival in siSNCG treated cells compared to siScr
treated cells. On the other hand, we established an in vitro model of SNCG
ectopic expression by using a triple-negative breast cancer cell line (SUM159PT)
to further investigate the radioprotective effect of SNCG. We showed that ectopic
expression of SNCG significantly decreased apoptosis of SUM159PT cells and
enhanced clonogenic cell survival after radiation treatment. At the molecular
level, after irradiation, the p53 pathway was less activated when SNCG was
present. Conversely, p21Waf1/Cip1 expression was upregulated in SNCG-expressing
cells. When p21 was down-regulated by siRNA, radiosensitivity of SNCG-expressing
SUM159PT cells was dramatically increased. This suggested a possible connection
between p21 and SNCG in radioresistance in these cells. In conclusion, our data
provide for the first time experimental evidence for the role of SNCG in the
radioresistance of breast cancer cells.
PMID- 29937997
TI - Metronomic combination of Vinorelbine and 5Fluorouracil is able to inhibit triple
negative breast cancer cells. Results from the proof-of-concept VICTOR-0 study.
AB - Triple Negative Breast Cancer (TNBC) is an aggressive neoplasia with median
Overall Survival (OS) less than two years. Despite the availability of new drugs,
the chance of survival of these patients did not increase. The combination of low
doses of drugs in a metronomic schedule showed efficacy in clinical trials,
exhibiting an anti-proliferative and anti-tumour activity. In Victor-2 study we
recently evaluated a new metronomic combination (mCHT) of Capecitabine (CAPE) and
Vinorelbine (VNR) in breast cancer patients showing a disease control rate with a
median Progression-Free Survival (PFS) of 4.7 months in 28 TNBC patients. Here in
Victor-0 study, we examined the effect of mCHT vs standard (STD) schedule of
administration of different combinations of 5-Fluorouracil (5FU), the active
metabolite of CAPE, and VNR in TNBC cell lines MDA-MB-231 and BT-549. A
significant anti-proliferative activity was observed in cells treated with
metronomic vs STD administration of 5FU or VNR alone. Combination of the two
drugs showed an additive inhibitor effect on cell growth in both cell lines.
Moreover, after exposure of cells to 5FU and VNR under mCHT or conventional
schedule of administration we also observed a downregulation of chemoresistance
factor Bcl-2, changes in pro-apoptotic protein Bax and in cleaved effector
caspase-3 and increased expression of LC3A/B autophagy protein. Our results
therefore suggest that molecular mechanisms implicated in apoptosis and autophagy
as well as the cross-talk between these two forms of cell death in MDA-MB-231 and
BT-549 cells treated with 5FU and VNR is dose- and schedule-dependent and provide
some insights about the roles of autophagy and senescence in 5FU/VNR-induced cell
death.
PMID- 29937998
TI - PD-L1 is expressed on human platelets and is affected by immune checkpoint
therapy.
AB - Cancer immunotherapy has been revolutionised by drugs that enhance the ability of
the immune system to detect and fight tumors. Immune checkpoint therapies that
target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown
unprecedented rates of durable clinical responses in patients with various cancer
types. However, there is still a large fraction of patients that do not respond
to checkpoint inhibitors, and the challenge remains to find cellular and
molecular cues that could predict which patients would benefit from these
therapies. Using a series of qualitative and quantitative methods we show here
that PBMCs and platelets from smokers and patients with head and neck squamous
cell carcinoma (HNSCC) or lung cancer express and up-regulate PD-L1 independently
of tumor stage. Furthermore, treatment with Atezolizumab, a fully humanised
monoclonal antibody against PD-L1, in 4 patients with lung cancer caused a
decrease in PD-L1 expression in platelets, which was restored over 20 days.
Altogether, our findings reveal the expression of the main therapeutic target in
current checkpoint therapies in human platelets and highlight their potential as
biomarkers to predict successful therapeutic outcomes.
PMID- 29937999
TI - Target amplicon exome-sequencing identifies promising diagnosis and prognostic
markers involved in RTK-RAS and PI3K-AKT signaling as central oncopathways in
primary central nervous system lymphoma.
AB - Exome-sequencing for somatic mutation detection and copy number variation
analysis are effective and valid methods for evaluating human cancers in current
molecular medicine. We conducted target amplicon exome-sequencing analyses using
PCR target enrichment and next-generation sequencing on Ion Proton semiconductor
sequencers. Twenty-seven primary central nervous system lymphoma (PCNSL)
specimens and their corresponding noncancerous tissues were used for multiplex
PCR amplification to obtain targeted coverages of the entire coding regions of
409 cancer-related genes. The average of the total numbers of somatic mutations
including single-nucleotide variations and insertion/deletion mutations in each
specimen was 13.3. Of these, the average of the ratios of nonsynonymous
substitutions in each specimen was 74.8%. The most frequent mutations in 27
specimens were in PIM1, MYD88, CD79B, DST, IRF4, ERBB3, MYH11, DCC, and KMT2D.
Furthermore, somatic mutations of MYH11 were related to poor prognoses in PCNSL
patients. Copy number variations were also duplicated and/or deleted from deep
sequencing in segmental genomic islands. In addition to these prognostic marker
candidates, analysis of RTK-RAS-MAPK signaling and the PTEN-PI3K-AKT proapoptotic
pathway showed that somatic activations and aberrations, respectively, may be
involved in a promising central oncopathway harboring mTOR, c-Myc, FOXO1, and
p53. This study provides a foundation for molecular targeted therapies based on
genome diagnostics and prognosis in PCNSL.
PMID- 29938001
TI - Sensitivity of pretargeted immunoPET using 68Ga-peptide to detect colonic
carcinoma liver metastases in a murine xenograft model: Comparison with 18FDG PET
CT.
AB - Purpose: The aim of this study was to compare the performances pretargeted
immunoPET 68Ga-PETimaging (68Ga-pPET) with anti carcino-embryonic antigen (CEA)
and anti-histamine-succinyl-glycine (HSG) recombinant humanized bispecific
monoclonal antibody (TF2) and 68Ga-labeled HSG peptide (IMP288) to conventional
18FDG-PET in an orthotopic murine model of liver metastases of human colonic
cancer. Methods: Hepatic tumor burden following intra-portal injection of
luciferase-transfected LS174T cells in nude mice was confirmed using
bioluminescence. One group of animals was injected intravenously with TF2 and
with 68Ga-IMP288 24 hours later (n=8). Another group received 18FDG (n=8), and a
third had both imaging modalities (n=7). PET acquisitions started 1 hour after
injection of the radioconjugate. Biodistributions in tumors and normal tissues
were assessed one hour after imaging. Results: Tumor/organ ratios were
significantly higher with 68Ga-pPET compared to 18FDG-PET (P<0.05) with both
imaging and biodistribution data. 68Ga-pPET sensitivity for tumor detection was
67% vs. 31% with 18FDG PET (P=0.049). For tumors less than 200 mg, the
sensitivity was 44% with 68Ga-pPET vs. 0% for 18FDG PET (P=0.031). A strong
correlation was demonstrated between tumor uptakes measured on PET images and
biodistribution analyses (r2=0.85). Conclusion: 68Ga-pPET was more sensitive than
18FDG-PET for the detection of human colonic liver metastases in an orthotopic
murine xenograft model. Improved tumor/organ ratios support the use of
pretargeting method for imaging and therapy of CEA-expressing tumors.
PMID- 29938000
TI - Anti-cancer binary system activated by bacteriophage HK022 integrase.
AB - The binary system presented in this work is based on the bacteriophage HK022
integrase recombinase that activates the expression of a silenced Diphtheria
toxin gene, both controlled by the cancer specific hTERT promoter. Using a lung
cancer mice model, assays of different apoptotic and anti-apoptotic factors have
demonstrated that the Integrase based binary system is highly specific towards
cancer cells and more efficient compared to the conventional mono system whose
toxin is directly expressed under hTERT. In a mice survival test, this binary
system demonstrated longer persistence compared to the untreated and the mono
treated ones. The reason underlying the advantage of this binary system over the
mono system seems to be an overexpression of various hTERT suppressing factors
induced by the mono system.
PMID- 29938002
TI - Protein expression patterns in cancer-associated fibroblasts and cells undergoing
the epithelial-mesenchymal transition in ovarian cancers.
AB - Recent studies have shown that cancer-associated fibroblasts (CAFs) and the
epithelial-mesenchymal transition (EMT) contribute to invasive and metastatic
abilities of ovarian cancer (OC) cells. In the present study, we attempted to
identify the role of CAF- and EMT-related proteins in OCs, including serous
carcinoma, mucinous carcinoma, endometrioid carcinoma and clear cell carcinoma
using an immunohistochemical approach. The following CAF-related markers were
used: CD10, podoplanin, fibroblast activating protein (FAP), platelet derived
growth factor receptor (PDGFRalpha), PDGFRbeta, S100A4 and alpha-smooth muscle
actin (alpha-SMA). In addition, the following EMT-related markers were
investigated: Slug, TWIST1 and ZEB1We performed hierarchical cluster analysis to
group the samples according to their scoring. Subgroup 1 was characterized by
high expression of CD10, podoplanin, alpha-SMA, Slug and ZEB1, whereas subgroup 2
was closely associated with high expression of podoplanin, PDGFRalpha, PDGFRbeta,
alpha-SMA, and Slug. In addition, marked expression of CD10 was observed in
subgroup 3. High expression of alpha-SMA was a distinctive feature in subgroup 4,
and expression of podoplanin and alpha-SMA characterized subgroup 5. Each
subgroup was correlated with a histological type. The fact that different
histological types were associated with different subgroups suggests the presence
of distinct and heterogeneous subpopulations of CAFs in OC.
PMID- 29938003
TI - Genetic alterations detected by comparative genomic hybridization in BRCAX breast
and ovarian cancers of Brazilian population.
AB - Background: About 5-10% of breast/ovarian cancers are hereditary. However, for a
large proportion of cases (around 50%), the genetic cause remains unknown. These
cases are grouped in a separated BRCAX category. The aim of this study was to
identify genomic alterations in BRCA1/BRCA2 wild-type tumor samples from women
with family history strongly suggestive of hereditary breast/ovarian cancer.
Results: A cohort of 31 Brazilian women was included in the study. Using the
GISTIC algorithm, we identified 20 regions with genomic gains and 31 with losses.
The most frequent altered regions were 1q21.2, 6p22.1 and 8p23.3 in breast tumors
and Xq26 and Xp22.32-22.31 among the ovarian cancer cases. An interesting
association identified was the loss of 22q13.31-13.32 and the presence of ovarian
cancer cases. Among the genes present in the frequently altered regions, we found
FGFR1, NSMCE2, CTTN, CRLF2, ERBB2, STARD3, MIR3201 and several genes of RAET and
ULBP family. Conclusions: In conclusion, our results suggest that alterations on
chromosomes 1, 6, 8 and X are common on BRCAX tumors and that the loss on 22q can
be associated with the presence of ovarian cancer. Methods: DNA copy number
alterations were analyzed by 60K array comparative genomic hybridization in
breast and ovarian FFPE tumors.
PMID- 29938004
TI - High miR-100 expression is associated with aggressive features and modulates
TORC1 complex activation in lung carcinoids.
AB - Purpose: Mammalian target of rapamycin (mTOR) is a promising therapeutic target
in advanced lung carcinoid patients. However, the mechanisms of mTOR modulation
and of responsiveness to mTOR inhibitors are largely unclear. Our aim was to
analyze the expression and functional role of specific miRNAs in lung carcinoids
as an alternative mechanism targeting mTOR pathway. Experimental design: Seven
miRNAs, selected by bioinformatic tools and literature search, were analyzed in
142 lung neuroendocrine neoplasms (92 carcinoids and a control group of 50 high
grade neuroendocrine carcinomas), and compared with mTOR mRNA expression and
clinical/pathological parameters. Tissue results were validated in vitro in two
lung carcinoid cell lines by specific RNA interference and
biological/pharmacological tests. Results: Tissutal expression of five miRNAs
(miR-99b, miR-100, miR-155, miR-193a-3p, miR-193a-5p) was inversely correlated
with mTOR mRNA expression, supporting their role in the negative regulation of
mTOR transcription. High expression of miR-100, miR-193a-3p and miR-193a-5p was
associated with aggressive features and, for the former two, with shorter time to
progression. In H727 and UMC11 lung carcinoid cells, miR-100 modulated mTOR RNA
and TORC1 complex protein expression, positively promoted cell migration and
negatively influenced cell proliferation. Moreover, miR-100 directly influenced
responsiveness of H727 and UMC11 cells to rapamycin. Conclusions: MiR-100
actively participates to the regulation of mTOR expression in lung carcinoids and
represents a novel candidate prognostic biomarker for this tumor type; moreover,
inhibition of its expression is associated to increased responsiveness to mTOR
inhibitors and might represent a novel strategy to sensitize lung carcinoids to
these target agents.
PMID- 29938005
TI - MutT homolog 1 counteracts the effect of anti-neoplastic treatments in adult and
pediatric glioblastoma cells.
AB - Glioblastoma, a fatal disease in both adult and pediatric patients, currently has
limited treatment options that offer no more than temporary relief. Our
experiments with adult and pediatric glioblastoma cell lines showed that
radiation induces a dose-dependent increase in the level of MutT homolog 1 (MTH1)
- an enzyme that hydrolyzes oxidized purine nucleoside triphosphates. Similarly,
the combination of vorinostat, which is a histone deacetylase inhibitor, and ABT
888, which is a PARP-1 inhibitor, enhanced clonogenic death and increased the
MTH1 level, relative to each treatment alone. This result suggests that the MTH1
level is directly related to the damage that is inflicted upon the cells, and its
activity protects them against anti-neoplastic therapy. Indeed, the MTH1
inhibitor TH588 and MTH1 siRNA increased glioblastoma's response to both
radiation and the combination of vorinostat and ABT-888. TH588 also inhibited
glioblastoma's capacity for migration and invasion. In normal fibroblasts, low
radiation doses and the combination of vorinostat and ABT-888 decreased the level
of the enzyme. TH588 did not alter the fibroblasts' response to radiation and
only mildly affected their response to the combination of vorinostat and ABT-888.
In summary, the inhibition of MTH1 is required to better realize the therapeutic
potential of anti-neoplastic treatments in glioblastoma.
PMID- 29938006
TI - Fertility-sparing surgery of malignant transformation arising from mature cystic
teratoma of the ovary.
AB - Background: The purpose of this study was to evaluate the long-term clinical
outcome of young women with malignant transformation arising from mature cystic
teratoma of the ovary (MT-MCT) by comparing radical surgery and fertility-sparing
surgery (FSS). Patients and methods: All patients treated with radical surgery or
FSS for MT-MCT in multiple institutions were registered in this analysis.
Univariate and multivariate analyses were performed to evaluate clinical outcome,
including overall survival (OS) and disease-free survival (DFS). Results: From
1986 to 2016, 62 patients with MT-MCT were treated in our group. The median
follow-up period was 38.0 (2.0-227.9) months, and the median age was 54 (17-82)
years old. Multivariate analysis revealed that only advanced stage was
significantly correlated with poorer prognosis of patients [hazard ratio (HR) for
death: 6.58, 95% confidence interval (CI): 1.82-24.78, P = 0.0048; HR for
recurrence: 5.59, 95% CI: 1.52-21.83, P = 0.01]. Of a total of 13 women with
stage I-II disease at less than 45 years old, 7 were treated with FSS, and there
was no recurrence except for in one woman with stage II MT-MCT. There was no
significant difference in long-term oncological outcome between radical surgery
and FSS. Conclusion: FSS may be indicated for patients with stage I MT-MCT, who
hope to preserve fertility, as no relapse was found after FSS.
PMID- 29938007
TI - CD300A promotes tumor progression by PECAM1, ADCY7 and AKT pathway in acute
myeloid leukemia.
AB - CD300A is a member of the CD300 glycoprotein family of cell surface proteins
involved in immune response signaling pathways. There is evidence that CD300A
plays a role in autophagy and angiogenesis, while, no studies have been reported
which investigated the role of CD300A in tumors. CD300A was found to be highly
expressed with statistical significance in acute myeloid leukemia (AML), as well
as associated with prognosis, through the analysis of differential expression
genes using the TCGA and GTEx database. A decrease in CD300A expression could
promote apoptosis and inhibit proliferation and migration of AML cell line U937,
as well as promote the activation of the AKT/mTOR pathway. These results
demonstrated that CD300A operated as a tumor promoter in AML cells. We further
analyzed coexpression genes of CD300A and then screened two genes, ADCY7 and
PECAM1, which were both overexpressed and associated with poor prognosis in AML.
Meanwhile, CD300A increased the expression of PECAM1 and ADCY7 in U937 cells.
Furthermore, we demonstrated that PECAM1 promoted the proliferation and migration
and inhibited the apoptosis of U937 cells. ADCY7 participated in the regulation
of proliferation and migration, but not apoptosis, in U937 cells. Both PECAM1 and
ADCY7 promoted tumor progression through the AKT pathway, showing the same
molecular mechanism as CD300A. To summarize, we, for the first time, confirmed
that CD300A promoted tumor progression by increase PECAM1 and ADCY7 expression,
and activating the AKT/mTOR signaling pathway in AML. It is suggested CD300A is
an oncogene and potential therapeutic target for AML.
PMID- 29938008
TI - Correction: 6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells
by activating PPAR-gamma.
AB - [This corrects the article DOI: 10.18632/oncotarget.16719.].
PMID- 29938009
TI - Application of data pooling to longitudinal studies of early post-traumatic
stress disorder (PTSD): the International Consortium to Predict PTSD (ICPP)
project.
AB - Background: Understanding the development of post-traumatic stress disorder
(PTSD) is a precondition for efficient risk assessment and prevention planning.
Studies to date have been site and sample specific. Towards developing
generalizable models of PTSD development and prediction, the International
Consortium to Predict PTSD (ICPP) compiled data from 13 longitudinal, acute-care
based PTSD studies performed in six different countries. Objective: The
objectives of this study were to describe the ICPP's approach to data pooling and
harmonization, and present cross-study descriptive results informing the
longitudinal course of PTSD after acute trauma. Methods: Item-level data from 13
longitudinal studies of adult civilian trauma survivors were collected.
Constructs (e.g. PTSD, depression), measures (questions or scales), and time
variables (days from trauma) were identified and harmonized, and those with
inconsistent coding (e.g. education, lifetime trauma exposure) were recoded.
Administered in 11 studies, the Clinician Administered PTSD Scale (CAPS) emerged
as the main measure of PTSD diagnosis and severity. Results: The pooled data set
included 6254 subjects (39.9% female). Studies' average retention rate was 87.0%
(range 49.1-93.5%). Participants' baseline assessments took place within 2 months
of trauma exposure. Follow-up durations ranged from 188 to 1110 days. Reflecting
studies' inclusion criteria, the prevalence of baseline PTSD differed
significantly between studies (range 3.1-61.6%), and similar differences were
observed in subsequent assessments (4.3-38.2% and 3.8-27.0% for second and third
assessments, respectively). Conclusion: Pooling data from independently collected
studies requires careful curation of individual data sets for extracting and
optimizing informative commonalities. However, it is an important step towards
developing robust and generalizable prediction models for PTSD and can exceed
findings of single studies. The large differences in prevalence of PTSD
longitudinally cautions against using any individual study to infer trauma
outcome. The multiplicity of instruments used in individual studies emphasizes
the need for common data elements in future studies.
PMID- 29938010
TI - The Parent Trauma Response Questionnaire (PTRQ): development and preliminary
validation.
AB - Background: Following a child's experience of trauma, parental response is
thought to play an important role in either facilitating or hindering their
psychological adjustment. However, the ability to investigate the role of
parenting responses in the post-trauma period has been hampered by a lack of
valid and reliable measures. Objectives: The aim of this study was to design, and
provide a preliminary validation of, the Parent Trauma Response Questionnaire
(PTRQ), a self-report measure of parental appraisals and support for children's
coping, in the aftermath of child trauma. Methods: We administered an initial set
of 78 items to 365 parents whose children, aged 2-19 years, had experienced a
traumatic event. We conducted principal axis factoring and then assessed the
validity of the reduced measure against a standardized general measure of
parental overprotection and via the measure's association with child post-trauma
mental health. Results: Factor analysis generated three factors assessing
parental maladaptive appraisals: (i) permanent change/damage, (ii) preoccupation
with child's vulnerability, and (iii) self-blame. In addition, five factors were
identified that assess parental support for child coping: (i) behavioural
avoidance, (ii) cognitive avoidance, (iii) overprotection, (iv) maintaining pre
trauma routines, and (v) approach coping. Good validity was evidenced against the
measure of parental overprotection and child post-traumatic stress symptoms. Good
test-retest reliability of the measure was also demonstrated. Conclusions: The
PTRQ is a valid and reliable self-report assessment of parenting cognitions and
coping in the aftermath of child trauma.
PMID- 29938011
TI - The enemy in the mirror: self-perception-induced stress results in dissociation
of psychological and physiological responses in patients with dissociative
disorder.
AB - Background: Patients suffering from dissociative disorders (DD) are characterized
by an avoidance of aversive stimuli. Clinical experience has shown that DD
patients typically avoid the confrontation with their own faces in a mirror
(CFM). Objective: To investigate potential CFM-associated self-reported and
psychophysiological stress reactions of DD patients, which most likely inform on
the still unknown pathophysiology of dysfunctional self-perception in DD. Method:
Eighteen DD patients and 18 healthy controls (HCs) underwent CFM. They were
assessed for CFM-induced subjective self-reported stress, acute dissociative
symptoms and sympathetic and parasympathetic drive using impedance cardiography.
Results: DD patients experienced more subjective stress and acute dissociation
than HCs upon CFM. Their psychological stress response did not activate the
sympathetic and parasympathetic nervous system. Conclusions: In DD patients, CFM
constitutes serious self-reported stress and is associated with a blunted
autonomic reactivity. Therapeutic approaches promoting self-perception and self
compassion, in particular by using CFM, might serve as goal-oriented diagnostic
and therapeutic tools in DD.
PMID- 29938012
TI - Correction for bias in meta-analysis of little-replicated studies.
AB - Meta-analyses conventionally weight study estimates on the inverse of their error
variance, in order to maximize precision. Unbiased variability in the estimates
of these study-level error variances increases with the inverse of study-level
replication. Here, we demonstrate how this variability accumulates asymmetrically
across studies in precision-weighted meta-analysis, to cause undervaluation of
the meta-level effect size or its error variance (the meta-effect and meta
variance).Small samples, typical of the ecological literature, induce big
sampling errors in variance estimation, which substantially bias precision
weighted meta-analysis. Simulations revealed that biases differed little between
random- and fixed-effects tests. Meta-estimation of a one-sample mean from 20
studies, with sample sizes of 3-20 observations, undervalued the meta-variance by
c. 20%. Meta-analysis of two-sample designs from 20 studies, with sample sizes of
3-10 observations, undervalued the meta-variance by 15%-20% for the log response
ratio (lnR); it undervalued the meta-effect by c. 10% for the standardized mean
difference (SMD).For all estimators, biases were eliminated or reduced by a
simple adjustment to the weighting on study precision. The study-specific
component of error variance prone to sampling error and not parametrically
attributable to study-specific replication was replaced by its cross-study mean,
on the assumptions of random sampling from the same population variance for all
studies, and sufficient studies for averaging. Weighting each study by the
inverse of this mean-adjusted error variance universally improved accuracy in
estimation of both the meta-effect and its significance, regardless of number of
studies. For comparison, weighting only on sample size gave the same improvement
in accuracy, but could not sensibly estimate significance.For the one-sample mean
and two-sample lnR, adjusted weighting also improved estimation of between-study
variance by DerSimonian-Laird and REML methods. For random-effects meta-analysis
of SMD from little-replicated studies, the most accurate meta-estimates obtained
from adjusted weights following conventionally weighted estimation of between
study variance.We recommend adoption of weighting by inverse adjusted-variance
for meta-analyses of well- and little-replicated studies, because it improves
accuracy and significance of meta-estimates, and it can extend the scope of the
meta-analysis to include some studies without variance estimates.
PMID- 29938013
TI - Analysis of nectar from low-volume flowers: A comparison of collection methods
for free amino acids.
AB - Floral nectar is a reward offered by flowering plants to visiting pollinators.
Nectar chemistry is important for understanding plant nutrient allocation and
plant-pollinator interactions. However, many plant species are difficult to
sample as their flowers are small and produce low amounts of nectar.We compared
the effects of different methods of nectar collection on the amino acid
composition of flowers with low volumes of nectar. We used five methods to
collect nectar from 60 (5 * 12) Calluna vulgaris flowers: microcapillary tubes, a
low-volume flower rinse (the micro-rinse method, using 2 MUl water), filter
paper, a high-volume flower rinse (2 ml water) and a flower wash (2 ml water). We
analysed the samples for free amino acids using quantitative UHPLC methods .We
found that the micro-rinse method (rinsing the nectary with enough water to only
cover the nectary) recovered amino acid proportions similar to raw nectar
extracted using microcapillary tubes. The filter paper, 2 ml rinse and 2 ml wash
methods measured significantly higher values of free amino acids and also altered
the profile of amino acids. We discuss our concerns about the increased
contamination risk of the filter paper and high-volume rinse and wash samples
from dried nectar across the floral tissue (nectar unavailable to floral
visitors), pollen, vascular fluid and cellular fluid.Our study will enable
researchers to make informed decisions about nectar collection methods depending
on their intended chemical analysis. These methods of sampling will enable
researchers to examine a larger array of plant species' flowers to include those
with low volumes of nectar.
PMID- 29938014
TI - TreeSimGM: Simulating phylogenetic trees under general Bellman-Harris models with
lineage-specific shifts of speciation and extinction in R.
AB - Understanding macroevolutionary processes using phylogenetic trees is a
challenging and complex process that draws on mathematics, computer science and
biology. Given the development of complex mathematical models and the growing
computational processing power, simulation tools are becoming increasingly
popular.In order to simulate phylogenetic trees, most evolutionary biologists are
forced to build their own algorithms or use existing tools built on different
platforms and/or as standalone programmes. The absence of a simulation tool
accommodating for user-chosen model specifications limits, amongst others, model
testing and pipelining with approximate Bayesian computation methods or other
subsequent statistical analysis.We introduce "TreeSimGM," an r-package simulation
tool for phylogenetic trees under a general Bellman and Harris model. This
package allows the user to specify any desired probability distribution for the
waiting times until speciation and extinction (e.g. age-dependent
speciation/extinction). Upon speciation, the user can specify whether one
descendant species corresponds to the ancestor species inheriting its age or
whether both descendant species are new species of age 0. Moreover, it is
possible to scale the waiting time to speciation/extinction for newly formed
species. Thus, "TreeSimGM" not only allows the user to simulate stochastic
phylogenetic trees assuming several popular existing models, such as the Yule
model, the constant-rate birth-death model, and proportional to distinguishable
arrangement models, but it also allows the user to formulate new models for
exploration. A short explanation of the supported models and a few examples of
how to use our package are presented here.As an r-package, "TreeSimGM" allows
flexible and powerful stochastic phylogenetic tree simulations. Moreover, it
facilitates the pipelining of outputs or inputs with other functions in r.
"TreeSimGM" contributes to the tools available to the r community in the fields
of ecology and evolution, is freely available under the GPL-2 licence and can be
downloaded at https://cran.r-project.org/web/packages/TreeSimGM.
PMID- 29938015
TI - A fast likelihood solution to the genetic clustering problem.
AB - The investigation of genetic clusters in natural populations is an ubiquitous
problem in a range of fields relying on the analysis of genetic data, such as
molecular ecology, conservation biology and microbiology. Typically, genetic
clusters are defined as distinct panmictic populations, or parental groups in the
context of hybridisation. Two types of methods have been developed for
identifying such clusters: model-based methods, which are usually computer
intensive but yield results which can be interpreted in the light of an explicit
population genetic model, and geometric approaches, which are less interpretable
but remarkably faster.Here, we introduce snapclust, a fast maximum-likelihood
solution to the genetic clustering problem, which allies the advantages of both
model-based and geometric approaches. Our method relies on maximising the
likelihood of a fixed number of panmictic populations, using a combination of
geometric approach and fast likelihood optimisation, using the Expectation
Maximisation (EM) algorithm. It can be used for assigning genotypes to
populations and optionally identify various types of hybrids between two parental
populations. Several goodness-of-fit statistics can also be used to guide the
choice of the retained number of clusters.Using extensive simulations, we show
that snapclust performs comparably to current gold standards for genetic
clustering as well as hybrid detection, with some advantages for identifying
hybrids after several backcrosses, while being orders of magnitude faster than
other model-based methods. We also illustrate how snapclust can be used for
identifying the optimal number of clusters, and subsequently assign individuals
to various hybrid classes simulated from an empirical microsatellite dataset.
snapclust is implemented in the package adegenet for the free software R, and is
therefore easily integrated into existing pipelines for genetic data analysis. It
can be applied to any kind of co-dominant markers, and can easily be extended to
more complex models including, for instance, varying ploidy levels. Given its
flexibility and computer-efficiency, it provides a useful complement to the
existing toolbox for the study of genetic diversity in natural populations.
PMID- 29938016
TI - How to use (and not to use) movement-based indices for quantifying foraging
behaviour.
AB - Movement-based indices such as moves per minute (MPM) and proportion time moving
(PTM) are common methodologies to quantify foraging behaviour. We explore
fundamental drawbacks of these indices that question the ways scientists have
been using them and propose new solutions.To do so, we combined analytical and
simulation models with lizards foraging data at the individual and species
levels.We found that the maximal value of MPM is constrained by the minimal
durations of moves and stops. As a result, foragers that rarely move and those
that rarely stop are bounded to similar low MPM values. This implies that (1) MPM
has very little meaning when used alone, (2) MPM and PTM are interdependent, and
(3) certain areas in the MPM-PTM plane cannot be occupied. We also found that MPM
suffers from inaccuracy and imprecision.We introduced a new bias correction
formula for already published MPM data, and a novel index of changes per minute
(CPM) that uses the frequency of changes between move and stop bouts. CPM is very
similar to MPM, but does not suffer from bias. Finally, we suggested a new
foraging plane of average move and average stop durations. We hope that our
guidelines of how to use (and not to use) movement-based indices will add rigor
to the study of animals' foraging behaviour.
PMID- 29938018
TI - Update on WSAVA's work on hereditary diseases.
PMID- 29938017
TI - Field methods for sampling tree height for tropical forest biomass estimation.
AB - Quantifying the relationship between tree diameter and height is a key component
of efforts to estimate biomass and carbon stocks in tropical forests. Although
substantial site-to-site variation in height-diameter allometries has been
documented, the time consuming nature of measuring all tree heights in an
inventory plot means that most studies do not include height, or else use generic
pan-tropical or regional allometric equations to estimate height.Using a pan
tropical dataset of 73 plots where at least 150 trees had in-field ground-based
height measurements, we examined how the number of trees sampled affects the
performance of locally derived height-diameter allometries, and evaluated the
performance of different methods for sampling trees for height measurement.Using
cross-validation, we found that allometries constructed with just 20 locally
measured values could often predict tree height with lower error than regional or
climate-based allometries (mean reduction in prediction error = 0.46 m). The
predictive performance of locally derived allometries improved with sample size,
but with diminishing returns in performance gains when more than 40 trees were
sampled. Estimates of stand-level biomass produced using local allometries to
estimate tree height show no over- or under-estimation bias when compared with
biomass estimates using field measured heights. We evaluated five strategies to
sample trees for height measurement, and found that sampling strategies that
included measuring the heights of the ten largest diameter trees in a plot
outperformed (in terms of resulting in local height-diameter models with low
height prediction error) entirely random or diameter size-class stratified
approaches.Our results indicate that even limited sampling of heights can be used
to refine height-diameter allometries. We recommend aiming for a conservative
threshold of sampling 50 trees per location for height measurement, and including
the ten trees with the largest diameter in this sample.
PMID- 29938019
TI - An eccentric rod-like linear connection of two heterocycles: synthesis of
pyridine trans-tetrafluoro-lambda6-sulfanyl triazoles.
AB - The trans-tetrafluoro-lambda6-sulfane (SF4) group has been utilized as a unique
three-dimensional building block for the linear connection of two independent N
heterocycles, pyridines and triazoles. The linearly connected heterocyclic
compounds were synthesized by thermal Huisgen 1,3-dipolar cycloaddition between
previously unknown pyridine SF4-alkynes and readily available azides, providing a
series of rod-like SF4-connected N-heterocycles in good to excellent yields. X
ray crystallographic analysis of the target products revealed the trans-geometry
of the SF4 group, which linearly connects two independent N-heterocycles. This
research will open the field of chemistry of SF4-connected heterocyclic
compounds.
PMID- 29938020
TI - A high spatiotemporal study of somatic exocytosis with scanning electrochemical
microscopy and nanoITIES electrodes.
AB - Extra-synaptic exocytosis is an essential component of cellular communication. A
knowledge gap exists in the exocytosis of the non-redox active transmitter
acetylcholine. Using the nano-interface between two immiscible electrolyte
solutions and scanning electrochemical microscopy (SECM), a high resolution
spatiotemporal study of acetylcholine exocytosis is shown from an individual
neuronal soma. The nanoelectrode was positioned ~140 nm away from the release
sites on the soma using an SECM. The quantitative study enables the obtaining of
key information related to cellular communication, including extracellular
concentration of the neurotransmitter, cellular permeability, Ca2+ dependence on
somatic release, vesicle density, number of molecules released and the release
dynamics. Measurements were achieved with a high signal to noise ratio of 6-19.
The released neurotransmitter with a concentration of 2.7 (+/-1.0) MUM was
detected at the nanoelectrodes with radii of 750 nm to 860 nm.
PMID- 29938021
TI - Controllable fabrication of bio-bar codes for dendritically amplified sensing of
human T-lymphotropic viruses.
AB - Human T-lymphotropic virus type II (HTLV-II) is an important type-C retrovirus,
closely related to a variety of human diseases. Here, we demonstrate for the
first time the controllable fabrication of bio-bar codes for dendritically
amplified sensing of low-abundant HTLV-II DNA by the integration of terminal
deoxynucleotidyl transferase (TdT)-catalyzed template-free polymerization
extension with bio-bar-code amplification (BCA). HTLV-II DNA hybridizes with
magnetic microparticle (MMP)-modified capture probe 1, forming a stable DNA
duplex with a protruding 3'-hydroxylated sequence which may function as a primer
to initiate the TdT-catalyzed first-step polymerization extension for the
generation of a poly-thymidine (T) sequence. The resultant poly-T products may
hybridize with poly-adenine (A) capture probe 2, inducing the self-assembly of
multiple capture probe 2-/reporter probe-functionalized Au nanoparticles (AuNPs)
onto the MMP. Subsequently, the reporter probes may act as the primers to
initiate the TdT-catalyzed second-step polymerization extension, producing large
numbers of G-rich DNAzymes for the generation of an enhanced chemiluminescence
signal. Taking advantage of the efficient polymerization extension reaction
catalyzed by TdT, the high amplification efficiency of BCA, and the intrinsically
high sensitivity of G-rich DNAzyme-driven chemiluminescence, this method exhibits
ultrahigh sensitivity with a limit of detection of as low as 0.50 aM and a large
dynamic range of 9 orders of magnitude from 1 aM to 1 nM. Moreover, this method
can be applied for the discrimination of a single-base mismatch and the
measurement of HTLV-II DNA in both human serum and human T-lymphocytic leukemia
cells, holding great potential in biomedical research and clinical diagnosis.
PMID- 29938022
TI - A flexible, redox-active macrocycle enables the electrocatalytic reduction of
nitrate to ammonia by a cobalt complex.
AB - The cobalt macrocycle complex [Co(DIM)Br2]+ (DIM = 2,3-dimethyl-1,4,8,11
tetraazacyclotetradeca-1,3-diene) is an electrocatalyst for the selective
reduction of nitrate to ammonia in aqueous solution. The catalyst operates over a
wide pH range and with very high faradaic efficiency, albeit with large
overpotential. Experimental investigations, supported by electronic structure
calculations, reveal that catalysis commences when nitrate binds to the two
electron reduced species CoII(DIM-), where cobalt and the macrocycle are each
reduced by a single electron. Several mechanisms for the initial reduction of
nitrate to nitrite were explored computationally and found to be feasible at room
temperature. The reduced DIM ligand plays an important role in these mechanisms
by directly transferring a single electron to the bound nitrate substrate,
activating it for further reactions. These studies further reveal that the DIM
macrocycle is critical to nitrate reduction, specifically its combination of
redox non-innocence, hydrogen-bonding functionality and flexibility in
coordination mode.
PMID- 29938023
TI - Molecularly precise self-assembly of theranostic nanoprobes within a single
molecular framework for in vivo tracking of tumor-specific chemotherapy.
AB - Structural heterogeneity and the lack of in vivo real-time tracking of drug
release are the utmost barriers for nanocarrier-mediated prodrugs in targeted
therapy. Herein, we describe the strategy of molecularly precise self-assembly of
monodisperse nanotheranostics for BP n -DCM-S-CPT (n = 0, 5 and 20) with fixed
drug loadings (36%, 23% and 16%) and constant release capacities, permitting in
vivo real-time targeted therapy. We focus on regulating the hydrophilic fragment
length to construct stable, well-defined nanostructured assemblies. Taking the
bis-condensed dicyanomethylene-4H-pyran (DCM) derivative as the activatable near
infrared (NIR) fluorophore, it makes full use of two terminal conjunctions: the
hydrophobic disulfide-bridged anticancer prodrug camptothecin (CPT) and the
hydrophilic oligomer-bridged biotin segment serving as an active targeting unit.
From the rational design, only BP20-DCM-S-CPT forms uniform and highly stable
self-assemblies (ca. 80 nm, critical micelle concentration = 1.52 MUM) with
several advantages, such as structural homogeneity, fixed drug loading
efficiency, real-time drug release tracking and synergistic targeting (passive,
active and activatable ability). More importantly, in vitro and in vivo
experiments verify that the surface-grafted biotins of nanoassemblies are
directly exposed to receptors on cancer cells, thus markedly facilitating
cellular internalization. Notably, through synergistic targeting, BP20-DCM-S-CPT
displays excellent tumor-specific drug release performance in HeLa tumor-bearing
nude mice, which has significantly enhanced in vivo antitumor activity and nearly
eradicates the tumor (IRT = 99.7%) with few side effects. For the first time, the
specific molecularly precise self-assembly of BP20-DCM-S-CPT within a single
molecular framework has successfully achieved a single reproducible entity for
real-time reporting of drug release and cancer therapeutic efficacy in living
animals, providing a new insight into amphiphilic nanotheranostics for clinical
translation.
PMID- 29938024
TI - Kekule diradicaloids derived from a classical N-heterocyclic carbene.
AB - The direct double carbenylation of 1,4-diiodobenzene and 4,4'-dibromobiphenyl
with a classical N-heterocyclic carbene, SIPr (1) (SIPr = :C{N(2,6
iPr2C6H3)}2CH2CH2), by means of nickel catalysis gives rise to 1,3-imidazolinium
salts [(SIPr)(C6H4)(SIPr)](I)2 (2) and [(SIPr)(C6H4)2(SIPr)](Br)2 (3) as off
white solids. Two-electron reduction of 2 and 3 with KC8 cleanly yields Kekule
diradicaloid compounds [(SIPr)(C6H4)(SIPr)] (4) and [(SIPr)(C6H4)2(SIPr)] (5),
respectively, as crystalline solids. Structural parameters and DFT as well as
CASSCF calculations suggest the closed-shell singlet ground state for 4 and 5.
Calculations reveal a very low singlet-triplet energy gap DeltaES-T for 5 (10.7
kcal mol-1), while DeltaES-T for 4 (29.1 kcal mol-1) is rather large.
PMID- 29938025
TI - Cobalt-catalysed alkene hydrogenation: a metallacycle can explain the hydroxyl
activating effect and the diastereoselectivity.
AB - Bis(phosphine)cobalt dialkyl complexes have been reported to be highly active in
the hydrogenation of tri-substituted alkenes bearing hydroxyl substituents.
Alkene substrates containing ether, ester, or ketone substituents show minimal
reactivity, indicating an activating effect of the hydroxyl group. The
mechanistic details of bis(phosphine)cobalt-catalysed hydrogenation were recently
evaluated computationally (X. Ma, M. Lei, J. Org. Chem. 2017, 82, 2703-2712) and
a Co(0)-Co(ii) redox mechanism was proposed. However, the activating effect of
the hydroxyl substituent and the accompanying high diastereoselectivity were not
studied. Here we report a computational study rationalizing the role of the
hydroxyl group through a key metallacycle species. The metallacycle is part of a
non-redox catalytic pathway proceeding through Co(ii) intermediates throughout.
The preference for alcohol over ether substrates and the high
diastereoselectivity of terpinen-4-ol hydrogenation are correctly predicted in
computations adopting the new pathway, whereas the alternative redox mechanism
predicts ethers rather than alcohols to be more reactive substrates. Additional
experimental evidence supports the role of the hydroxyl group in the metallacycle
mechanism. Our work highlights the importance of employing known substrate
preferences and stereoselectivities to test the validity of computationally
proposed reaction pathways.
PMID- 29938026
TI - Direct evidence of catalyst reduction on dye and catalyst co-sensitized NiO
photocathodes by mid-infrared transient absorption spectroscopy.
AB - Co-sensitization of molecular dyes and catalysts on semiconductor surfaces is a
promising strategy to build photoelectrodes for solar fuel production. In such a
photoelectrode, understanding the charge transfer reactions between the molecular
dye, catalyst and semiconductor material is key to guide further improvement of
their photocatalytic performance. Herein, femtosecond mid-infrared transient
absorption spectroscopy is used, for the first time, to probe charge transfer
reactions leading to catalyst reduction on co-sensitized nickel oxide (NiO)
photocathodes. The NiO films were co-sensitized with a molecular dye and a proton
reducing catalyst from the family of [FeFe](bdt)(CO)6 (bdt = benzene-1,2
dithiolate) complexes. Two dyes were used: an organic push-pull dye denoted E2
with a triarylamine-oligothiophene-dicyanovinyl structure and a coumarin 343 dye.
Upon photo-excitation of the dye, a clear spectroscopic signature of the reduced
catalyst is observed a few picoseconds after excitation in all co-sensitized NiO
films. However, kinetic analysis of the transient absorption signals of the dye
and reduced catalyst reveal important mechanistic differences in the first
reduction of the catalyst depending on the co-sensitized molecular dye (E2 or
C343). While catalyst reduction is preceded by hole injection in NiO in C343
sensitized NiO films, the singly reduced catalyst is formed by direct electron
transfer from the excited dye E2* to the catalyst in E2-sensitized NiO films.
This change in mechanism also impacts the lifetime of the reduced catalyst, which
is only ca. 50 ps in E2-sensitized NiO films but is >5 ns in C343-sensitized NiO
films. Finally, the implication of this mechanistic study for the development of
better co-sensitized photocathodes is discussed.
PMID- 29938028
TI - Thermodynamic and reactivity studies of a tin corrole-cobalt porphyrin
heterobimetallic complex.
AB - A heterobimetallic complex, (TPFC)Sn-Co(TAP) (TPFC = 5,10,15
tris(pentafluorophenyl)corrole, TAP = 5,10,15,20-tetrakis(p
methoxyphenyl)porphyrin), was synthesized. The complex featured a Sn-Co bond with
a bond dissociation enthalpy (BDE) of 30.2 +/- 0.9 kcal mol-1 and a bond
dissociation Gibbs free energy (BDFE) of 21.0 +/- 0.2 kcal mol-1, which underwent
homolysis to produce the (TPFC)Sn radical and (TAP)CoII under either heat or
visible light irradiation. The novel tin radical (TPFC)Sn, being the first four
coordinate tin radical observed at room temperature, was studied
spectroscopically and computationally. (TPFC)Sn-Co(TAP) promoted the
oligomerization of aryl alkynes to give the insertion products (TPFC)Sn-(CH
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Co(TAP) (n = 1, 2, or 3) as well as 1,3,5-triarylbenzenes. Mechanistic studies
revealed a radical chain mechanism involving the (TPFC)Sn radical as the key
intermediate.
PMID- 29938027
TI - Cu-catalyzed enantioselective synthesis of tertiary benzylic copper complexes and
their in situ addition to carbonyl compounds.
AB - Catalytic chemo- and enantioselective generation of tertiary benzylic copper
complexes from Cu-B(pin) (pin = pinacolato) additions to 1,1-disubstituted
alkenes followed by in situ reactions with ketones and carboxylic acid phenol
esters to construct multifunctional alkylboron compounds that contain quaternary
stereogenic centers is presented. The method is distinguished by the
unprecedented reaction mode of tertiary benzylic Cu complexes, allowing reaction
with a wide range of carbonyl electrophiles in good yields and with high chemo-,
site-, diastereo- and enantioselectivity. The catalytic protocol was performed
with easily accessible chiral ligands and copper salts at ambient temperature.
Functionalization of multifunctional alkylboron products provides useful building
blocks that are otherwise difficult to access.
PMID- 29938029
TI - Trimerisation of carbon suboxide at a di-titanium centre to form a pyrone ring
system.
AB - The reaction of the syn-bimetallic bis(pentalene)dititanium complex
Ti2(MU:eta5,eta5-Pn?)2 (Pn? = C8H4(1,4-SiiPr3)2) 1 with carbon suboxide (O
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results in trimerisation of the latter and formation of the structurally
characterised complex [{Ti2(MU:eta5,eta5-Pn?)2}{MU-C9O6}]. The trimeric bridging
C9O6 unit in the latter contains a 4-pyrone core, a key feature of both the
hexamer and octamer of carbon suboxide which are formed in the body from trace
amounts of C3O2 and are, for example, potent inhibitors of Na+/K+-ATP-ase. The
mechanism of this reaction has been studied in detail by DFT computational
studies, which also suggest that the reaction proceeds via the initial formation
of a mono-adduct of 1 with C3O2. Indeed, the carefully controlled reaction of 1
with C3O2 affords [Ti2(MU:eta5,eta5-Pn?)2 (eta2-C3O2)], as the first structurally
authenticated complex of carbon suboxide.
PMID- 29938030
TI - A supramolecular radical cation: folding-enhanced electrostatic effect for
promoting radical-mediated oxidation.
AB - We report a supramolecular strategy to promote radical-mediated Fenton oxidation
by the rational design of a folded host-guest complex based on cucurbit[8]uril
(CB[8]). In the supramolecular complex between CB[8] and a derivative of 1,4
diketopyrrolo[3,4-c]pyrrole (DPP), the carbonyl groups of CB[8] and the DPP
moiety are brought together through the formation of a folded conformation. In
this way, the electrostatic effect of the carbonyl groups of CB[8] is fully
applied to highly improve the reactivity of the DPP radical cation, which is the
key intermediate of Fenton oxidation. As a result, the Fenton oxidation is
extraordinarily accelerated by over 100 times. It is anticipated that this
strategy could be applied to other radical reactions and enrich the field of
supramolecular radical chemistry in radical polymerization, photocatalysis, and
organic radical battery and holds potential in supramolecular catalysis and
biocatalysis.
PMID- 29938032
TI - Electrical and SERS detection of disulfide-mediated dimerization in single
molecule benzene-1,4-dithiol junctions.
AB - We applied a combination of mechanically controllable break junction (MCBJ) and
in situ surface enhanced Raman spectroscopy (SERS) methods to investigate the
long-standing single-molecule conductance discrepancy of prototypical benzene-1,4
dithiol (BDT) junctions. Single-molecule conductance characterization, together
with configuration analysis of the molecular junction, suggested that disulfide
mediated dimerization of BDT contributed to the low conductance feature, which
was further verified by the detection of S-S bond formation through in situ SERS
characterization. Control experiments demonstrated that the disulfide-mediated
dimerization could be tuned via the chemical inhibitor. Our findings suggest that
a combined electrical and SERS method is capable of probing chemical reactions at
the single-molecule level.
PMID- 29938031
TI - Formation of a new type of uranium(iv) poly-oxo cluster {U38} based on a
controlled release of water via esterification reaction.
AB - A new strategy for the synthesis of large poly-oxo clusters bearing 38
tetravalent uranium atoms {U38} has been developed by controlling the water
release from the esterification reaction between a carboxylic acid and an
alcohol. The molecular entity [U38O56Cl40(H2O)2(ipa)20].(ipa) x (ipa =
isopropanol) was crystallized from the solvothermal reaction of a mixture of UCl4
and benzoic acid in isopropanol at temperature ranging from 70 to 130 degrees C.
Its crystal structure reveals the molecular assembly of the UO2 fluorite-like
inner core {U14} with oxo groups bridging the uranium centers. The {U14} core is
further surrounded by six tetrameric sub-units of {U4} to form the {U38} cluster.
Its surface is decorated by either bridging- and terminal chloride anions or
terminal isopropanol molecules. Another synthesis using the same reactant mixture
at room temperature resulted in the crystallization of a discrete dinuclear
complex [U2Cl4(bz)4(ipa)4].(ipa)0.5 (bz = benzoate), in which each uranium center
is coordinated by two chlorine atoms, four oxygen atoms from carboxylate groups
and two additional oxygen atoms from isopropanol. The slow production of water
released from the esterification of isopropanol allows the formation of the giant
cluster with oxo bridges linking the uranium atoms at a temperature above 70
degrees C, whereas no such oxo groups are present in the dinuclear complex formed
at room temperature. The kinetics of {U38} crystallization as well as the ester
formation are analyzed and discussed. SAXS experiments indicate that the {U38}
species are not dominant in the supernatant, but hexanuclear entities which are
closely related to the [U6O8] type are formed.
PMID- 29938033
TI - A DFT-based mechanistic proposal for the light-driven insertion of dioxygen into
Pt(ii)-C bonds.
AB - The photocatalyzed insertion of dioxygen into the Pt(ii)-methyl bond in
terpyridine platinum complexes has been shown to proceed efficiently, but its
mechanism remains a challenge. In particular, there are serious counter-intuitive
differences in the reactivity of structurally similar complexes. M06 calculations
in solvent with a valence double-zeta basis set supplemented by polarization and
diffusion shells (benchmarked against omegaB97x-D calculations with a larger
basis set) are able to provide a satisfactory mechanistic answer. The proposed
mechanism starts with the absorption of a photon by the metal complex, which then
evolves into a triplet state that reacts with the triplet dioxygen fragment. A
variety of possible reaction paths have been identified, some leading to the
methylperoxo product and others reverting to the reactants, and the validity of
some of these paths has been confirmed by additional experiments. The balance
between the barriers towards productive and unproductive paths reproduces the
diverging experimental behavior of similar complexes and provides a general
mechanistic picture for these processes.
PMID- 29938034
TI - Bithiazolidinylidene polymers: synthesis and electronic interactions with
transition metal dichalcogenides.
AB - We describe the synthesis of electron acceptors consisting of
bithiazolidinylidene (BT) derivatives incorporated into solution processible
polymers. Novel BT-containing polymers displayed p-doping behavior when in
contact with the n-type transition metal dichalcogenide (TMDC) MoS2. A work
function (WF) increase of MoS2, resulting from contact with BT polymers, was
measured by Kelvin probe force microscopy (KPFM), representing the first example
of polymer p-doping of MoS2, which is beneficial for advancing the design of
electronically tailored TMDCs.
PMID- 29938035
TI - Enantioselective synthesis of amines by combining photoredox and enzymatic
catalysis in a cyclic reaction network.
AB - Visible light-driven reduction of imines to enantioenriched amines in aqueous
solution is demonstrated for the first time. Excitation of a new water-soluble
variant of the widely used [Ir(ppy)3] (ppy = 2-phenylpyridine) photosensitizer in
the presence of a cyclic imine affords a highly reactive alpha-amino alkyl
radical that is intercepted by hydrogen atom transfer (HAT) from ascorbate or
thiol donors to afford the corresponding amine. The enzyme monoamine oxidase (MAO
N-9) selectively catalyzes the oxidation of one of the enantiomers to the
corresponding imine. Upon combining the photoredox and biocatalytic processes
under continuous photo-irradiation, enantioenriched amines are obtained in
excellent yields. To the best of our knowledge, this is the first demonstration
of a concurrent photoredox- and enzymatic catalysis leading to a light-driven
asymmetric synthesis of amines.
PMID- 29938036
TI - Metal-free borylative dearomatization of indoles: exploring the divergent
reactivity of aminoborane C-H borylation catalysts.
AB - While the dearomatization of indoles by carbon-boron bond forming reactions is
new and quite promising, they are so far mainly metal-catalyzed. Here, we
establish the use of metal-free catalysts in promoting such reactions in an atom
efficient way. The in situ generated ambiphilic aminoborane catalyst (1-Pip-2-BH2
C6H4)2 (Pip = piperidyl) promotes borylative dearomatization of various 1
arylsulfonyl indoles with pinacolborane in a syn addition fashion, with H and
Bpin groups added respectively to the 2 and 3 positions of indoles. Catalysis
proceeds with good to excellent conversion and essentially with complete regio-
and diastereoselectivity. From mechanistic insights and DFT computations, we
realized and established that prototypical boranes can also catalyze this
borylative dearomatization.
PMID- 29938037
TI - The chemical identity, state and structure of catalytically active centers during
the electrochemical CO2 reduction on porous Fe-nitrogen-carbon (Fe-N-C)
materials.
AB - We report novel structure-activity relationships and explore the chemical state
and structure of catalytically active sites under operando conditions during the
electrochemical CO2 reduction reaction (CO2RR) catalyzed by a series of porous
iron-nitrogen-carbon (FeNC) catalysts. The FeNC catalysts were synthesized from
different nitrogen precursors and, as a result of this, exhibited quite distinct
physical properties, such as BET surface areas and distinct chemical N
functionalities in varying ratios. The chemical diversity of the FeNC catalysts
was harnessed to set up correlations between the catalytic CO2RR activity and
their chemical nitrogen-functionalities, which provided a deeper understanding
between catalyst chemistry and function. XPS measurements revealed a dominant
role of porphyrin-like Fe-N x motifs and pyridinic nitrogen species in catalyzing
the overall reaction process. Operando EXAFS measurements revealed an unexpected
change in the Fe oxidation state and associated coordination from Fe2+ to Fe1+.
This redox change coincides with the onset of catalytic CH4 production around
0.9 VRHE. The ability of the solid state coordinative Fe1+-N x moiety to form
hydrocarbons from CO2 is remarkable, as it represents the solid-state analogue to
molecular Fe1+ coordination compounds with the same catalytic capability under
homogeneous catalytic environments. This finding highlights a conceptual bridge
between heterogeneous and homogenous catalysis and contributes significantly to
our fundamental understanding of the FeNC catalyst function in the CO2RR.
PMID- 29938038
TI - Rhodium-catalyzed asymmetric hydroamination and hydroindolation of keto
vinylidenecyclopropanes.
AB - We reported a highly regio- and enantioselective hydroamination and
hydroindolation of keto-vinylidenecyclopropanes via cationic Rh(i) catalysis in
this context. The combination of various secondary amines and indoles with keto
vinylidenecyclopropanes afforded the corresponding hydrofunctionalization
products in good to excellent yields with outstanding ee values under mild
conditions. A new TMM-Rh model complex was proposed, providing an atom economical
Rh-pi-allyl precursor at the same time. Moreover, the resulting products could
easily be transformed into more complex polyheterocycles upon further synthetic
manipulation.
PMID- 29938039
TI - Enantioselective radical process for synthesis of chiral indolines by
metalloradical alkylation of diverse C(sp3)-H bonds.
AB - A new C-C bond formation strategy based on enantioselective radical alkylation of
C(sp3)-H bonds via Co(ii)-based metalloradical catalysis has been demonstrated
for stereoselective synthesis of chiral indolines. The Co(ii)-based system
enables activation of aryldiazomethanes as radical precursors at room temperature
for enantioselective intramolecular radical alkylation of broad types of C-H
bonds, constructing 2-substituted indolines in high yields with excellent
enantioselectivities. In addition to chemoselectivity and regioselectivity, this
Co(ii)-catalyzed alkylation features tolerance to functional groups and
compatibility with heteroaryl substrates. Detailed mechanistic studies provide
insight into the underlying stepwise radical pathway.
PMID- 29938040
TI - The robust, readily available cobalt(iii) trication [Co(NH2CHPhCHPhNH2)3]3+ is a
progenitor of broadly applicable chirality and prochirality sensing agents.
AB - When NMR spectra of chiral racemic organic molecules containing a Lewis basic
functional group are recorded in the presence of air and water stable salts of
the cobalt(iii) trication [Co((S,S)-NH2CHPhCHPhNH2)3]3+ (23+), separate signals
are usually observed for the enantiomers (28 diverse examples, >12 functional
groups). Several chiral molecules can be simultaneously analyzed, and
enantiotopic groups in prochiral molecules differentiated (16 examples).
Particularly effective are the mixed bis(halide)/tetraarylborate salts Lambda-23+
2X-BArf- (X = Cl, I; BArf = B(3,5-C6H3(CF3)2)4), which are applied in CD2Cl2 or
CDCl3 at 1-100 mol% (avg 34 and 14 mol%). Job plots establish 1 : 1 binding for
Lambda-23+ 2Cl-BArf- and 1-phenylethyl acetate (4) or 1-phenylethanol (10), and
ca. 1 : 2 binding with DMSO (CD2Cl2). Selected binding constants are determined,
which range from 7.60-2.73 M-1 for the enantiomers of 10 to 28.1-22.6 M-1 for the
enantiomers of 4. The NH moieties of the C2 faces of the trication are believed
to hydrogen bond to the Lewis basic functional groups, as seen in the crystal
structure of a hexakis(DMSO) solvate of Lambda-23+ 3I-. These salts rank with the
most broadly applicable chirality sensing agents discovered to date.
PMID- 29938041
TI - Curved pi-conjugated corannulene dimer diradicaloids.
AB - So far, most reported open-shell singlet diradicaloids are based on planar pi
conjugated molecules. Herein, we report the bridged corannulene dimer
diradicaloids, Cor-D1 and Cor-D2, both showing a three-dimensional curved pi
conjugated structure. Cor-D1 has a small diradical character (y0 = 5.4%) and
behaves more like a closed-shell quinoidal compound at room temperature, while
Cor-D2 is a typical open-shell diradicaloid with a larger diradical character (y0
= 16.9%). Both compounds exhibited paramagnetic activity at elevated
temperatures, with a singlet-triplet energy gap (DeltaES-T) of -8.4 and -3.0 kcal
mol-1, respectively. X-ray crystallographic analysis revealed that both molecules
have a dumbbell-shaped geometry, with the two terminal corannulene bowls bent to
opposite directions. The spin is largely delocalized onto the two bowls in Cor-D2
and there are multiple [CH...pi] interactions between the neighboring bowls.
Chemical oxidation/reduction to their respective dications/dianions results in
global aromaticity with [4n + 2] pi-electrons delocalized through the periphery
of the whole framework.
PMID- 29938042
TI - Extraordinary water adsorption characteristics of graphene oxide.
AB - The laminated structure of graphene oxide (GO) confers unique interactions with
water molecules which may be utilised in a range of applications that require
materials with tuneable hygroscopic properties. The precise role of the
expandable interlayer spacing and functional groups in GO laminates has not
completely been understood to date. Herein, we report the experimental and
theoretical investigations on the adsorption and desorption behaviour of water in
GO laminates as a function of relative pressure. We observed that GO imparts high
water uptake capacity of up to 0.58 gram of water per gram of GO (g g-1), which
is significantly higher than silica gel as a conventional desiccant material.
More interestingly, the adsorption and desorption kinetics of GO is five times
higher than silica gel. The observed extraordinary adsorption/desorption rate can
be attributed to the high capillary pressure in GO laminates as well as micro
meter sized tunnel-like wrinkles located at the surface.
PMID- 29938043
TI - Blue light-promoted photolysis of aryldiazoacetates.
AB - Aryldiazoacetates can undergo photolysis under blue light irradiation (460-490
nm) at room temperature and under air in the presence of numerous trapping
agents, such as styrene, carboxylic acids, amines, alkanes and arenes, thus
providing a straighforward and general platform for their mild functionalization.
PMID- 29938044
TI - Pop-Inference: An educational application to evaluate statistical differences
among populations.
AB - Pop-Inference is an educational tool designed to help teaching of hypothesis
testing using populations. The application allows for the statistical comparison
of demographic parameters among populations. Input demographic data are
projection matrices or raw demographic data. Randomization tests are used to
compare populations. The tests evaluate the hypothesis that demographic
parameters differ among groups of individuals more that should be expected from
random allocation of individuals to populations. Confidence intervals for
demographic parameters are obtained using the bootstrap. Tests may be global or
pairwise. In addition to tests on differences, one-way life table response
experiments (LTRE) are available for random and fixed factors. Planned (a priori)
comparisons are possible. Power of comparison tests is evaluated by constructing
the distribution of the test statistic when the null hypothesis is true and when
it is false. The relationship between power and sample size is explored by
evaluating differences among populations at increasing population sizes, while
keeping vital rates constant.
PMID- 29938045
TI - Which is more biased: Standardized weather stations or microclimatic sensors?
AB - Linked Article: https://doi.org/10.1002/ece3.3972.
PMID- 29938046
TI - Accurate near surface air temperature measurements are necessary to gauge large
scale ecological responses to global climate change.
AB - Linked Article: https://doi.org/10.1002/ece3.3965.
PMID- 29938047
TI - Quantification of pathogen levels is necessary to compare responses to pathogen
exposure: Comment on Davy et al. "The other white-nose syndrome transcriptome".
AB - When studying host responses to the presence of pathogens, the pathogen levels
should be verified within the samples. The RNA-Seq samples from Davy et al.
(2017) do not contain detectable Pseudogymnoascus destructans pathogen levels
compared to other studies. Future studies will be necessary to determine how
hosts resistant to white-nose syndrome respond differently than susceptible hosts
at the whole-transcriptome level. Linked Article:
https://doi.org/10.1002/ece3.4035.
PMID- 29938048
TI - Environmentally persistent pathogens present unique challenges for studies of
host-pathogen interactions: Reply to Field (2018).
AB - Linked article: https://doi.org/10.1002/ece3.4034.
PMID- 29938049
TI - Symbiotic flagellate protists as cryptic drivers of adaptation and invasiveness
of the subterranean termite Reticulitermes grassei Clement.
AB - Changes in flagellate protist communities of subterranean termite Reticulitermes
grassei across different locations were evaluated following four predictions: (i)
Rural endemic (Portugal mainland) termite populations will exhibit high diversity
of symbionts; (ii) invasive urban populations (Horta city, Faial island, Azores),
on the contrary, will exhibit lower diversity of symbionts, showing high
similarity of symbiont assemblages through environmental filtering; (iii) recent
historical colonization of isolated regions-as the case of islands-will imply a
loss of symbiont diversity; and (iv) island isolation will trigger a change in
colony breeding structure toward a less aggressive behavior. Symbiont flagellate
protist communities were morphologically identified, and species richness and
relative abundances, as well as biodiversity indices, were used to compare
symbiotic communities in colonies from urban and rural environments and between
island invasive and mainland endemic populations. To evaluate prediction on the
impact of isolation (iv), aggression tests were performed among termites
comprising island invasive and mainland endemic populations. A core group of
flagellates and secondary facultative symbionts was identified. Termites from
rural environments showed, in the majority of observed colonies, more diverse and
abundant protist communities, probably confirming prediction (i). Corroborating
prediction (ii), the two least diverse communities belong to termites captured
inside urban areas. The Azorean invasive termite colonies had more diverse
protist communities than expected and prediction (iii) which was not verified
within this study. Termites from mainland populations showed a high level of
aggressiveness between neighboring colonies, in contrast to the invasive colonies
from Horta city, which were not aggressive to neighbors according to prediction
(iv). The symbiotic flagellate community of R. grassei showed the ability to
change in a way that might be consistent with adaptation to available conditions,
possibly contributing to optimization of the colonization of new habitats and
spreading of its distribution area, highlighting R. grassei potential as an
invasive species.
PMID- 29938050
TI - A biogeographical profile of the sand cockroach Arenivaga floridensis and its
bearing on origin hypotheses for Florida scrub biota.
AB - Florida scrub is a xeric ecosystem associated with the peninsula's sand ridges,
whose intermittent Pliocene-Pleistocene isolation is considered key to scrub
endemism. One scrub origin hypothesis posits endemics were sourced by the
Pliocene dispersal of arid-adapted taxa from southwestern North America; a second
invokes Pleistocene migration within eastern North America. Only one study to
date has explicitly tested these competing hypotheses, supporting an eastern
origin for certain scrub angiosperms. For further perspective, we conducted a
genetic analysis of an endemic arthropod, the Florida sand cockroach (Arenivaga
floridensis), with two aims: (1) to reconstruct the peninsular colonization and
residence history of A. floridensis and (2) determine whether its biogeographic
profile favors either origin hypothesis. We sequenced the cox2 mitochondrial gene
for 237 specimens (65 populations) as well as additional loci (cox1, nuclear H3)
for a subset of Florida roaches and congeners. Using Network and Bayesian
inference methods, we identified three major lineages whose genetic
differentiation and phylogeographical structure correspond with late Pliocene
peninsula insularization, indicating Arenivaga was present and broadly
distributed in Florida at that time. Stem and crown divergence estimates (6.36
Ma; 2.78 Ma) between A. floridensis and western sister taxa span a period of
extensive dispersal by western biota along an arid Gulf Coast corridor. These
phylogeographical and phylogenetic results yield a biogeographic profile
consistent with the western origin hypothesis. Moreover, age estimates for the
roach's peninsular residence complement those of several other endemics, favoring
a Pliocene (or earlier) inception of the scrub ecosystem. We argue that eastern
versus western hypotheses are not mutually exclusive; rather, a composite history
of colonization involving disparate biotas better explains the diverse endemism
of Florida scrub.
PMID- 29938051
TI - Effects of increased temperature on plant communities depend on landscape
location and precipitation.
AB - Global climate change is affecting and will continue to affect ecosystems
worldwide. Specifically, temperature and precipitation are both expected to shift
globally, and their separate and interactive effects will likely affect
ecosystems differentially depending on current temperature, precipitation
regimes, and other biotic and environmental factors. It is not currently
understood how the effects of increasing temperature on plant communities may
depend on either precipitation or where communities lie on soil moisture
gradients. Such knowledge would play a crucial role in increasing our predictive
ability for future effects of climate change in different systems. To this end,
we conducted a multi-factor global change experiment at two locations, differing
in temperature, moisture, aspect, and plant community composition, on the same
slope in the northern Mongolian steppe. The natural differences in temperature
and moisture between locations served as a point of comparison for the
experimental manipulations of temperature and precipitation. We conducted two
separate experiments, one examining the effect of climate manipulation via open
top chambers (OTCs) across the two different slope locations, the other a
factorial OTC by watering experiment at one of the two locations. By combining
these experiments, we were able to assess how OTCs impact plant productivity and
diversity across a natural and manipulated range of soil moisture. We found that
warming effects were context dependent, with the greatest negative impacts of
warming on diversity in the warmer, drier upper slope location and in the
unwatered plots. Our study is an important step in understanding how global
change will affect ecosystems across multiple scales and locations.
PMID- 29938052
TI - Estimation of fitness from energetics and life-history data: An example using
mussels.
AB - Changing environments have the potential to alter the fitness of organisms
through effects on components of fitness such as energy acquisition, metabolic
cost, growth rate, survivorship, and reproductive output. Organisms, on the other
hand, can alter aspects of their physiology and life histories through phenotypic
plasticity as well as through genetic change in populations (selection).
Researchers examining the effects of environmental variables frequently
concentrate on individual components of fitness, although methods exist to
combine these into a population level estimate of average fitness, as the per
capita rate of population growth for a set of identical individuals with a
particular set of traits. Recent advances in energetic modeling have provided
excellent data on energy intake and costs leading to growth, reproduction, and
other life-history parameters; these in turn have consequences for survivorship
at all life-history stages, and thus for fitness. Components of fitness alone
(performance measures) are useful in determining organism response to changing
conditions, but are often not good predictors of fitness; they can differ in both
form and magnitude, as demonstrated in our model. Here, we combine an energetics
model for growth and allocation with a matrix model that calculates population
growth rate for a group of individuals with a particular set of traits. We use
intertidal mussels as an example, because data exist for some of the important
energetic and life-history parameters, and because there is a hypothesized
energetic trade-off between byssus production (affecting survivorship), and
energy used for growth and reproduction. The model shows exactly how strong this
trade-off is in terms of overall fitness, and it illustrates conditions where
fitness components are good predictors of actual fitness, and cases where they
are not. In addition, the model is used to examine the effects of environmental
change on this trade-off and on both fitness and on individual fitness
components.
PMID- 29938053
TI - Influence of invasion history on rapid morphological divergence across island
populations of an exotic bird.
AB - There is increasing evidence that exotic populations may rapidly differentiate
from those in their native range and that differences also arise among
populations within the exotic range. Using morphological and DNA-based analyses,
we document the extent of trait divergence among native North American and exotic
Hawaiian populations of northern cardinal (Cardinalis cardinalis). Furthermore,
using a combination of historical records and DNA-based analyses, we evaluate the
role of founder effects in producing observed trait differences. We measured and
compared key morphological traits across northern cardinal populations in the
native and exotic ranges to assess whether trait divergence across the Hawaiian
Islands, where this species was introduced between 1929 and 1931, reflected
observed variation across native phylogeographic clades in its native North
America. We used and added to prior phylogenetic analyses based on a
mitochondrial locus to identify the most likely native source clade(s) for the
Hawaiian cardinal populations. We then used Approximate Bayesian Computation
(ABC) to evaluate the role of founder effects in producing the observed
differences in body size and bill morphology across native and exotic
populations. We found cardinal populations on the Hawaiian Islands had
morphological traits that diverged substantially across islands and overlapped
the trait space of all measured native North American clades. The phylogeographic
analysis identified the eastern North American clade (C. cardinalis cardinalis)
as the most likely and sole native source for all the Hawaiian cardinal
populations. The ABC analyses supported written accounts of the cardinal's
introduction that indicate the original 300 cardinals shipped to Hawaii were
simultaneously and evenly released across Hawaii, Kauai, and Oahu. Populations on
each island likely experienced bottlenecks followed by expansion, with cardinals
from the island of Hawaii eventually colonizing Maui unaided. Overall, our
results suggest that founder effects had limited impact on morphological trait
divergence of exotic cardinal populations in the Hawaiian archipelago, which
instead reflect postintroduction events.
PMID- 29938054
TI - Comparing the rates of speciation and extinction between phylogenetic trees.
AB - Over the past decade or so it has become increasingly popular to use
reconstructed evolutionary trees to investigate questions about the rates of
speciation and extinction. Although the methodology of this field has grown
substantially in its sophistication in recent years, here I will take a step back
to present a very simple model that is designed to investigate the relatively
straightforward question of whether the tempo of diversification (speciation and
extinction) differs between two or more phylogenetic trees, without attempting to
attribute a causal basis to this difference. It is a likelihood method, and I
demonstrate that it generally shows type I error that is close to the nominal
level. I also demonstrate that parameter estimates obtained with this approach
are largely unbiased. As this method can be used to compare trees of unknown
relationship, it will be particularly well-suited to problems in which a
difference in diversification rate between clades is suspected, but in which
these clades are not particularly closely related. As diversification methods can
easily take into account an incomplete sampling fraction, but missing lineages
are assumed to be missing at random, this method is also appropriate for cases in
which we have hypothesized a difference in the process of diversification between
two or more focal clades, but in which many unsampled groups separate the few of
interest. The method of this study is by no means an attempt to replace more
sophisticated models in which, for instance, diversification depends on the state
of an observed or unobserved discrete or continuous trait. Rather, my intention
is to provide a complementary approach for circumstances in which a simpler
hypothesis is warranted and of biological interest.
PMID- 29938055
TI - When phylogeny and ecology meet: Modeling the occurrence of Trichoptera with
environmental and phylogenetic data.
AB - Ecological studies are increasingly considering phylogenetic relationships among
species. The phylogeny is used as a proxy or filter to improve statistical tests
and retain evolutionary elements, such as niche conservation. We used the
phylogenetic topology to improve the model for occurrence of Trichoptera genera
in Cerrado (Brazilian Savanna) streams. We tested whether parameters generated by
logistic models of occurrence, using phylogenetic signals, are better than models
generated without phylogenetic information. We used a model with Bayesian
updating to examine the influence of stream water pH and phylogenetic
relationship among genera on the occurrence of Trichoptera genera. Then, we
compared this model with the logistic model for each Trichoptera genus. The
probability of occurrence of most genera increased with water pH, and the
phylogeny-based explicit logistic model improved the parameters estimated for
observed genera. The inferred relationship between genera occurrence and stream
pH improved, indicating that phylogeny adds relevant information when estimating
ecological responses of organisms. Water with elevated acidity (low pH values)
may be restrictive for the occurrence of Trichoptera larvae, especially if the
regional streams exhibit neutral to alkaline water, as is observed in the Cerrado
region. Using phylogeny-based modeling to predict species occurrence is a
prominent opportunity to extend our current statistical framework based on
environmental conditions, as it enables a more precise estimation of ecological
parameters.
PMID- 29938056
TI - Insights into the phylogenetic and molecular evolutionary histories of Fad and
Elovl gene families in Actiniaria.
AB - The biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs, >= C20) is
reliant on the action of desaturase and elongase enzymes, which are encoded by
the fatty acyl desaturase (Fad) and elongation of very long-chain fatty acid
(Elovl) gene families, respectively. In Metazoa, research investigating the
distribution and evolution of these gene families has been restricted largely to
Bilateria. Here, we provide insights into the phylogenetic and molecular
evolutionary histories of the Fad and Elovl gene families in Cnidaria, the sister
phylum to Bilateria. Four model cnidarian genomes and six actiniarian
transcriptomes were interrogated. Analysis of the fatty acid composition of a
candidate cnidarian species, Actinia tenebrosa, was performed to determine the
baseline profile of this species. Phylogenetic analysis revealed lineage-specific
gene duplication in actiniarians for both the Fad and Elovl gene families. Two
distinct cnidarian Fad clades clustered with functionally characterized Delta5
and Delta6 proteins from fungal and plant species, respectively. Alternatively,
only a single cnidarian Elovl clade clustered with functionally characterized
Elovl proteins (Elovl4), while two additional clades were identified, one
actiniarian-specific (Novel ElovlA) and the another cnidarian-specific (Novel
ElovlB). In actiniarians, selection analyses revealed pervasive purifying
selection acting on both gene families. However, codons in the Elovl gene family
show patterns of nucleotide variation consistent with the action of episodic
diversifying selection following gene duplication events. Significantly, these
codons may encode amino acid residues that are functionally important for Elovl
proteins to target and elongate different precursor fatty acids. In A. tenebrosa,
the fatty acid analysis revealed an absence of LC-PUFAs > C20 molecules and
implies that the Elovl enzymes are not actively contributing to the elongation of
these LC-PUFAs. Overall, this study has revealed that actiniarians possess Fad
and Elovl genes required for the biosynthesis of some LC-PUFAs, and that these
genes appear to be distinct from bilaterians.
PMID- 29938057
TI - A spatial genetics approach to inform vector control of tsetse flies (Glossina
fuscipes fuscipes) in Northern Uganda.
AB - Tsetse flies (genus Glossina) are the only vector for the parasitic trypanosomes
responsible for sleeping sickness and nagana across sub-Saharan Africa. In
Uganda, the tsetse fly Glossina fuscipes fuscipes is responsible for transmission
of the parasite in 90% of sleeping sickness cases, and co-occurrence of both
forms of human-infective trypanosomes makes vector control a priority. We use
population genetic data from 38 samples from northern Uganda in a novel
methodological pipeline that integrates genetic data, remotely sensed
environmental data, and hundreds of field-survey observations. This
methodological pipeline identifies isolated habitat by first identifying
environmental parameters correlated with genetic differentiation, second,
predicting spatial connectivity using field-survey observations and the most
predictive environmental parameter(s), and third, overlaying the connectivity
surface onto a habitat suitability map. Results from this pipeline indicated that
net photosynthesis was the strongest predictor of genetic differentiation in G.
f. fuscipes in northern Uganda. The resulting connectivity surface identified a
large area of well-connected habitat in northwestern Uganda, and twenty-four
isolated patches on the northeastern margin of the G. f. fuscipes distribution.
We tested this novel methodological pipeline by completing an ad hoc sample and
genetic screen of G. f. fuscipes samples from a model-predicted isolated patch,
and evaluated whether the ad hoc sample was in fact as genetically isolated as
predicted. Results indicated that genetic isolation of the ad hoc sample was as
genetically isolated as predicted, with differentiation well above estimates made
in samples from within well-connected habitat separated by similar geographic
distances. This work has important practical implications for the control of
tsetse and other disease vectors, because it provides a way to identify isolated
populations where it will be safer and easier to implement vector control and
that should be prioritized as study sites during the development and improvement
of vector control methods.
PMID- 29938058
TI - Phylogenetic signal in tooth wear dietary niche proxies.
AB - In the absence of independent observational data, ecologists and paleoecologists
use proxies for the Eltonian niches of species (i.e., the resource or dietary
axes of the niche). Some dietary proxies exploit the fact that mammalian teeth
experience wear during mastication, due to both tooth-on-tooth and food-on-tooth
interactions. The distribution and types of wear detectible at micro- and
macroscales are highly correlated with the resource preferences of individuals
and, in turn, species. Because methods that quantify the distribution of tooth
wear (i.e., analytical tooth wear methods) do so by direct observation of facets
and marks on the teeth of individual animals, dietary inferences derived from
them are thought to be independent of the clade to which individuals belong.
However, an assumption of clade or phylogenetic independence when making species
level dietary inferences may be misleading if phylogenetic niche conservatism is
widespread among mammals. Herein, we test for phylogenetic signal in data from
numerous analytical tooth wear studies, incorporating macrowear (i.e., mesowear)
and microwear (i.e., low-magnification microwear and dental microwear texture
analysis). Using two measures of phylogenetic signal, heritability (H2) and
Pagel's lambda, we find that analytical tooth wear data are not independent of
phylogeny and failing to account for such nonindependence leads to overestimation
of discriminability among species with different dietary preferences. We suggest
that morphological traits inherited from ancestral clades (e.g., tooth shape)
influence the ways in which the teeth wear during mastication and constrain the
foods individuals of a species can effectively exploit. We do not suggest that
tooth wear is simply phylogeny in disguise; the tooth wear of individuals and
species likely varies within some range that is set by morphological constraints.
We therefore recommend the use of phylogenetic comparative methods in studies of
mammalian tooth wear, whenever possible.
PMID- 29938059
TI - Can the narrow red bands of dragonflies be used to perceive wing interference
patterns?
AB - Despite numerous studies of selection on position and number of spectral vision
bands, explanations to the function of narrow spectral bands are lacking. We
investigate dragonflies (Odonata), which have the narrowest spectral bands
reported, in order to investigate what features these narrow spectral bands may
be used to perceive. We address whether it is likely that narrow red bands can be
used to identify conspecifics by the optical signature from wing interference
patterns (WIPs). We investigate the optical signatures of Odonata wings using
hyperspectral imaging, laser profiling, ellipsometry, polarimetric modulation
spectroscopy, and laser radar experiments. Based on results, we estimate the
prospects for Odonata perception of WIPs to identify conspecifics in the
spectral, spatial, intensity, polarization, angular, and temporal domains. We
find six lines of evidence consistent with an ability to perceive WIPs. First,
the wing membrane thickness of the studied Odonata is 2.3 MUm, coinciding with
the maximal thickness perceivable by the reported bandwidth. Second, flat wings
imply that WIPs persist from whole wings, which can be seen at a distance. Third,
WIPs constitute a major brightness in the visual environment only second after
the solar disk. Fourth, WIPs exhibit high degree of polarization and polarization
vision coincides with frontal narrow red bands in Odonata. Fifth, the angular
light incidence on the Odonata composite eye provides all prerequisites for
direct assessment of the refractive index which is associated with age. Sixth,
WIPs from conspecifics in flight make a significant contribution even to the
fundamental wingbeat frequency within the flicker fusion bandwidth of Odonata
vision. We conclude that it is likely that WIPs can be perceived by the narrow
red bands found in some Odonata species and propose future behavioral and
electrophysiological tests of this hypothesis.
PMID- 29938060
TI - Dietary choices are influenced by genotype, mating status, and sex in Drosophila
melanogaster.
AB - Mating causes many changes in physiology, behavior, and gene expression in a wide
range of organisms. These changes are predicted to be sex specific, influenced by
the divergent reproductive roles of the sexes. In female insects, mating is
associated with an increase in egg production which requires high levels of
nutritional input with direct consequences for the physiological needs of
individual females. Consequently, females alter their nutritional acquisition in
line with the physiological demands imposed by mating. Although much is known
about the female mating-induced nutritional response, far less is known about
changes in males. In addition, it is unknown whether variation between genotypes
translates into variation in dietary behavioral responses. Here we examine mating
induced shifts in male and female dietary preferences across genotypes of
Drosophila melanogaster. We find sex- and genotype-specific effects on both the
quantity and quality of the chosen diet. These results contribute to our
understanding of sex-specific metabolism and reveal genotypic variation that
influences responses to physiological demands.
PMID- 29938061
TI - The genetic network of greater sage-grouse: Range-wide identification of keystone
hubs of connectivity.
AB - Genetic networks can characterize complex genetic relationships among groups of
individuals, which can be used to rank nodes most important to the overall
connectivity of the system. Ranking allows scarce resources to be guided toward
nodes integral to connectivity. The greater sage-grouse (Centrocercus
urophasianus) is a species of conservation concern that breeds on spatially
discrete leks that must remain connected by genetic exchange for population
persistence. We genotyped 5,950 individuals from 1,200 greater sage-grouse leks
distributed across the entire species' geographic range. We found a small-world
network composed of 458 nodes connected by 14,481 edges. This network was
composed of hubs-that is, nodes facilitating gene flow across the network-and
spokes-that is, nodes where connectivity is served by hubs. It is within these
hubs that the greatest genetic diversity was housed. Using indices of network
centrality, we identified hub nodes of greatest conservation importance. We also
identified keystone nodes with elevated centrality despite low local population
size. Hub and keystone nodes were found across the entire species' contiguous
range, although nodes with elevated importance to network-wide connectivity were
found more central: especially in northeastern, central, and southwestern Wyoming
and eastern Idaho. Nodes among which genes are most readily exchanged were mostly
located in Montana and northern Wyoming, as well as Utah and eastern Nevada. The
loss of hub or keystone nodes could lead to the disintegration of the network
into smaller, isolated subnetworks. Protecting both hub nodes and keystone nodes
will conserve genetic diversity and should maintain network connections to ensure
a resilient and viable population over time. Our analysis shows that network
models can be used to model gene flow, offering insights into its pattern and
process, with application to prioritizing landscapes for conservation.
PMID- 29938062
TI - Molecular signatures of host specificity linked to habitat specialization in
Exaiptasia sea anemones.
AB - Rising ocean temperatures associated with global climate change induce breakdown
of the symbiosis between coelenterates and photosynthetic microalgae of the genus
Symbiodinium. Association with more thermotolerant partners could contribute to
resilience, but the genetic mechanisms controlling specificity of hosts for
particular Symbiodinium types are poorly known. Here, we characterize wild
populations of a sea anemone laboratory model system for anthozoan symbiosis,
from contrasting environments in Caribbean Panama. Patterns of anemone abundance
and symbiont diversity were consistent with specialization of holobionts for
particular habitats, with Exaiptasia pallida/S. minutum (ITS2 type B1) abundant
on vertical substrate in thermally stable, shaded environments but E.
brasiliensis/Symbiodinium sp. (ITS2 clade A) more common in shallow areas subject
to high temperature and irradiance. Population genomic sequencing revealed a
novel E. pallida population from the Bocas del Toro Archipelago that only harbors
S. minutum. Loci most strongly associated with divergence of the Bocas-specific
population were enriched in genes with putative roles in cnidarian symbiosis,
including activators of the complement pathway of the innate immune system,
thrombospondin-type-1 repeat domain proteins, and coordinators of endocytic
recycling. Our findings underscore the importance of unmasking cryptic diversity
in natural populations and the role of long-term evolutionary history in
mediating interactions with Symbiodinium.
PMID- 29938063
TI - Genetic diversity and colony structure of Tapinoma melanocephalum on the islands
and mainland of South China.
AB - Aim: Tapinoma melanocephalum is listed as one of the most important invasive pest
species in China. Information regarding the patterns of invasion and effects of
geographic isolation on the population genetics of this species is largely
lacking. Location: South China. Methods: To address this problem, we genotyped 39
colonies (two colonies were collapsed due to genetic similarity) using
microsatellite markers and mitochondrial DNA sequencing to compare colony genetic
structure of T. melanocephalum on the mainland and islands of South China.
Results: An analysis of the colony genotypes showed that the genetic diversity of
the mainland population was slightly higher than that of the island populations
but not significantly so. However, the observed heterozygosity on Shangchuan
Island (SCD) was significantly lower than that of the other colonies. We also
found six haplotypes in 111 mitochondrial DNA COI sequences. The relatedness (r)
value between colonies of SCD was 0.410, higher than that of the other
populations. The genetic clusters among colonies were not related to geographic
locations and exhibited admixture likely due to frequent human-mediated dispersal
associated with trade between the mainland population and the islands. Pairwise
FSTs between populations showed differentiation among mainland populations, while
SCD displayed high levels of divergence (FST > 0.15) from most mainland
populations. There was no significant isolation by distance among colonies. Most
populations showed signs of a bottleneck effect. Main conclusions: Our study
suggests that there was no significant difference in the genetic diversity among
the islands and the mainland; however, the lower genetic diversity, the higher
degree of genetic divergence from other colonies, and the higher relatedness
among nestmates made the SCD population stand out from all the others.
PMID- 29938065
TI - Does reproductive isolation reflect the segregation of color forms in Spiranthes
sinensis (Pers.) Ames complex (Orchidaceae) in the Chinese Himalayas?
AB - Isolation between species, or taxa sharing a common lineage, depends primarily on
the relative strengths of various reproductive barriers. Previous studies on
reproductive isolation between orchids emphasized mechanical and ethological
barriers in flowers of species showing food and/or sexual mimicry. In this study,
we investigated and quantified a series of prepollination and postpollination
barriers between pink and white forms of Spiranthes sinensis sl, a nectar
secreting complex. We generated ML trees based on trnS-G and matK to explore
phylogenetic relationships in this species complex. Spiranthes sinensis sl
segregated from some other congeners, but the white form constituted a distinct
clade in relation to the pink form. The white form secreted 2-Phenylethanol as it
is a single-scent compound and was pollinated almost exclusively by native, large
bodied Apis cerana and Bombus species (Apidae). Apis cerana showed a high floral
constancy to this form. The scentless, pink form was pollinated primarily by
smaller bees in the genera Ceratina (Apidae), and members of the family
Halictidae, with infrequent visits by A. cerana and Bombus species. Fruit set and
the production of large embryos following interform pollination treatments were
significantly lower compared to intraform pollination results for the white form.
Our results suggested that pollinator isolation, based on color and scent cues,
may result in greater floral constancy in white populations when both forms are
sympatric as two different, guilds of pollinators forage selectively preventing
or reducing prospective gene flow. Postpollination barriers appear weaker than
prepollination barriers but they also play a role in interform isolation,
especially in the white form. Our findings suggest that floral color forms in S.
sinensis do not represent an unbalanced polymorphism. Interpretations of the
evolutionary status of these forms are discussed.
PMID- 29938066
TI - Studying the quantity component of seed dispersal effectiveness from exclosure
treatments and camera trapping.
AB - The quantity component of effectiveness of seed dispersal by animals is
determined by two events: fruit removal (intensity of the interaction) and animal
visitation to the plant (frequency of interactions). Considering dispersal of
Prosopis flexuosa seeds as case study, this work aimed at investigating the
strengths and weaknesses of the two methods for assessing the quantity component
of seed dispersal effectiveness: exclosures and camera traps. Prosopis fruits
were offered for 48 hr. Exclosure treatments were performed using two types of
wire-screen cages, allowing access to ants ("closed exclosure") and to small
mammals up to 100 g ("open to small mammals"), and a treatment without exclosure
("open to all removers"). The camera trapping experiment was carried out using
vertically oriented cameras placed at approximately 1.80 m height and focused on
the fruits. The cameras were set in "motion detect mode," taking series of three
consecutive photographs. The exclosures largely allowed estimation of fruit
removal by size-based groups of animals, but did not provide information on
species identity. In contrast, camera traps were able to identify all visitors to
species level and could not only determine the number of visits by each species
but also the proportion of visits, which resulted in removal of fruits. Camera
trapping allowed discriminating among small mammals playing different roles,
without underestimating fruit removal by scatter-hoarding species. The quality of
estimation of the quantity component of seed dispersal is remarkably better when
the camera trapping method is applied. Additional information obtained, such as
activity patterns of visitors, can contribute to a better understanding of the
seed dispersal process.
PMID- 29938064
TI - Wolbachia enhances insect-specific flavivirus infection in Aedes aegypti
mosquitoes.
AB - Mosquitoes transmit a diverse group of human flaviviruses including West Nile,
dengue, yellow fever, and Zika viruses. Mosquitoes are also naturally infected
with insect-specific flaviviruses (ISFs), a subgroup of the family not capable of
infecting vertebrates. Although ISFs are not medically important, they are
capable of altering the mosquito's susceptibility to flaviviruses and may alter
host fitness. Wolbachia is an endosymbiotic bacterium of insects that when
present in mosquitoes limits the replication of co-infecting pathogens, including
flaviviruses. Artificially created Wolbachia-infected Aedes aegypti mosquitoes
are being released into the wild in a series of trials around the globe with the
hope of interrupting dengue and Zika virus transmission from mosquitoes to
humans. Our work investigated the effect of Wolbachia on ISF infection in wild
caught Ae. aegypti mosquitoes from field release zones. All field mosquitoes were
screened for the presence of ISFs using general degenerate flavivirus primers and
their PCR amplicons sequenced. ISFs were found to be common and widely
distributed in Ae. aegypti populations. Field mosquitoes consistently had higher
ISF infection rates and viral loads compared to laboratory colony material
indicating that environmental conditions may modulate ISF infection in Ae.
aegypti. Surprisingly, higher ISF infection rates and loads were found in
Wolbachia-infected mosquitoes compared to the Wolbachia-free mosquitoes. Our
findings demonstrate that the symbiont is capable of manipulating the mosquito
virome and that Wolbachia-mediated viral inhibition is not universal for
flaviviruses. This may have implications for the Wolbachia-based DENV control
strategy if ISFs confer fitness effects or alter mosquito susceptibility to other
flaviviruses.
PMID- 29938067
TI - An exploration of differences in the scaling of life history traits with body
mass within reptiles and between amniotes.
AB - Allometric relationships linking species characteristics to body size or mass
(scaling) are important in biology. However, studies on the scaling of life
history traits in the reptiles (the nonavian Reptilia) are rather scarce,
especially for the clades Crocodilia, Testudines, and Rhynchocephalia (single
extant species, the tuatara). Previous studies on the scaling of reptilian life
history traits indicated that they differ from those seen in the other amniotes
(mammals and birds), but so far most comparative studies used small species
samples and also not phylogenetically informed analyses. Here, we analyzed the
scaling of nine life history traits with adult body mass for crocodiles (n = 22),
squamates (n = 294), turtles (n = 52), and reptiles (n = 369). We used for the
first time a phylogenetically informed approach for crocodiles, turtles, and the
whole group of reptiles. We explored differences in scaling relationships between
the reptilian clades Crocodilia, Squamata, and Testudines as well as differences
between reptiles, mammals, and birds. Finally, we applied our scaling
relationships, in order to gain new insights into the degree of the
exceptionality of the tuatara's life history within reptiles. We observed for
none of the life history traits studied any difference in their scaling with body
mass between squamates, crocodiles, and turtles, except for clutch size and egg
weight showing small differences between these groups. Compared to birds and
mammals, scaling relationships of reptiles were similar for time-related traits,
but they differed for reproductive traits. The tuatara's life history is more
similar to that of a similar-sized turtle or crocodile than to a squamate.
PMID- 29938069
TI - Habitat connectivity is determined by the scale of habitat loss and dispersal
strategy.
AB - Understanding factors that ameliorate the impact of habitat loss is a major focus
of conservation research. One key factor influencing species persistence and
evolution is the ability to disperse across increasingly patchy landscapes. Here
we ask whether interpatch distance (a proxy for habitat loss) and dispersal
strategy can interact to form thresholds where connectivity breaks down. We
assayed dispersal across a range of interpatch distances in fruit flies carrying
allelic variants of a gene known to underlie differences in dispersal strategy.
Dispersal-limited flies experienced a distinct negative threshold in connectivity
at greater interpatch distances, and this was not observed in more dispersive
flies. Consequently, this differential response of dispersal-limited and more
dispersive flies to decreasing connectivity suggests that habitat loss could have
important implications on the evolution and maintenance of genetic variation
underlying dispersal strategy.
PMID- 29938068
TI - Gene(s) and individual feeding behavior: Exploring eco-evolutionary dynamics
underlying left-right asymmetry in the scale-eating cichlid fish Perissodus
microlepis.
AB - The scale-eating cichlid fish Perissodus microlepis is a textbook example of
bilateral asymmetry due to its left or right-bending heads and of negative
frequency-dependent selection, which is proposed to maintain this stable
polymorphism. The mechanisms that underlie this asymmetry remain elusive. Several
studies had initially postulated a simple genetic basis for this trait, but this
explanation has been questioned, particularly by reports observing a unimodal
distribution of mouth shapes. We hypothesize that this unimodal distribution
might be due to a combination of genetic and phenotypically plastic components.
Here, we expanded on previous work by investigating a formerly identified
candidate SNP associated to mouth laterality, documenting inter-individual
variation in feeding preference using stable isotope analyses, and testing their
association with mouth asymmetry. Our results suggest that this polymorphism is
influenced by both a polygenic basis and inter-individual non-genetic variation,
possibly due to feeding experience, individual specialization, and intraspecific
competition. We introduce a hypothesis potentially explaining the simultaneous
maintenance of left, right, asymmetric and symmetric mouth phenotypes due to the
interaction between diverse eco-evolutionary dynamics including niche
construction and balancing selection. Future studies will have to further tease
apart the relative contribution of genetic and environmental factors and their
interactions in an integrated fashion.
PMID- 29938070
TI - Nightjars may adjust breeding phenology to compensate for mismatches between
moths and moonlight.
AB - Phenology match-mismatch usually refers to the extent of an organism's ability to
match reproduction with peaks in food availability, but when mismatch occurs, it
may indicate a response to another selective pressure. We assess the value of
matching reproductive timing to multiple selective pressures for a migratory
lunarphilic aerial insectivore bird, the whip-poor-will (Antrostomus vociferus).
We hypothesize that a whip-poor-will's response to shifts in local phenology may
be constrained by long annual migrations and a foraging mode that is dependent on
both benign weather and the availability of moonlight. To test this, we monitored
daily nest survival and overall reproductive success relative to food
availability and moon phase in the northern part of whip-poor-will's breeding
range. We found that moth abundance, and potentially temperature and moonlight,
may all have a positive influence on daily chick survival rates and that the
lowest chick survival rates for the period between hatching and fledging occurred
when hatch was mismatched with both moths and moonlight. However, rather than
breeding too late for peak moth abundance, the average first brood hatch date
actually preceded the peak moth abundance and occurred during a period with
slightly higher available moonlight than the period of peak food abundance. As a
result, a low individual survival rate was partially compensated for by
initiating more nesting attempts. This suggests that nightjars were able to
adjust their breeding phenology in such a way that the costs of mismatch with
food supply were at least partially balanced by a longer breeding season.
PMID- 29938071
TI - Shrimp ponds lead to massive loss of soil carbon and greenhouse gas emissions in
northeastern Brazilian mangroves.
AB - Mangroves of the semiarid Caatinga region of northeastern Brazil are being
rapidly converted to shrimp pond aquaculture. To determine ecosystem carbon
stocks and potential greenhouse gas emissions from this widespread land use, we
measured carbon stocks of eight mangrove forests and three shrimp ponds in the
Acarau and Jaguaribe watersheds in Ceara state, Brazil. The shrimp ponds were
paired with adjacent intact mangroves to ascertain carbon losses and potential
emissions from land conversion. The mean total ecosystem carbon stock of
mangroves in this semiarid tropical landscape was 413 +/- 94 Mg C/ha. There were
highly significant differences in the ecosystem carbon stocks between the two
sampled estuaries suggesting caution when extrapolating carbon stock across
different estuaries even in the same landscape. Conversion of mangroves to shrimp
ponds resulted in losses of 58%-82% of the ecosystem carbon stocks. The mean
potential emissions arising from mangrove conversion to shrimp ponds was 1,390 Mg
CO2e/ha. Carbon losses were largely from soils which accounted for 81% of the
total emission. Losses from soils >100 cm in depth accounted for 33% of the total
ecosystem carbon loss. Soil carbon losses from shrimp pond conversion are
equivalent to about 182 years of soil carbon accumulation. Losses from mangrove
conversion are about 10-fold greater than emissions from conversion of upland
tropical dry forest in the Brazilian Caatinga underscoring the potential value
for their inclusion in climate change mitigation activities.
PMID- 29938072
TI - Biofilm formation and toxin production provide a fitness advantage in mixed
colonies of environmental yeast isolates.
AB - Microbes can engage in social interactions ranging from cooperation to warfare.
Biofilms are structured, cooperative microbial communities. Like all cooperative
communities, they are susceptible to invasion by selfish individuals who benefit
without contributing. However, biofilms are pervasive and ancient, representing
the first fossilized life. One hypothesis for the stability of biofilms is
spatial structure: Segregated patches of related cooperative cells are able to
outcompete unrelated cells. These dynamics have been explored computationally and
in bacteria; however, their relevance to eukaryotic microbes remains an open
question. The complexity of eukaryotic cell signaling and communication suggests
the possibility of different social dynamics. Using the tractable model yeast,
Saccharomyces cerevisiae, which can form biofilms, we investigate the
interactions of environmental isolates with different social phenotypes. We find
that biofilm strains spatially exclude nonbiofilm strains and that biofilm
spatial structure confers a consistent and robust fitness advantage in direct
competition. Furthermore, biofilms may protect against killer toxin, a warfare
phenotype. During biofilm formation, cells are susceptible to toxin from nearby
competitors; however, increased spatial use may provide an escape from toxin
producers. Our results suggest that yeast biofilms represent a competitive
strategy and that principles elucidated for the evolution and stability of
bacterial biofilms may apply to more complex eukaryotes.
PMID- 29938073
TI - Cracking the case: Seed traits and phylogeny predict time to germination in
prairie restoration species.
AB - Traits are important for understanding how plant communities assemble and
function, providing a common currency for studying ecological processes across
species, locations, and habitat types. However, the majority of studies relating
species traits to community assembly rely upon vegetative traits of mature
plants. Seed traits, which are understudied relative to whole-plant traits, are
key to understanding assembly of plant communities. This is particularly true for
restored communities, which are typically started de novo from seed, making seed
germination a critical first step in community assembly and an early filter for
plant establishment. We experimentally tested the effects of seed traits (mass,
shape, and embryo to seed size ratio) and phylogeny on germination response in 32
species commonly used in prairie grassland restoration in the Midwestern USA,
analyzing data using time-to-event (survival) analysis. As germination is also
influenced by seed dormancy, and dormancy break treatments are commonly employed
in restoration, we also tested the effects of two pretreatments (cold
stratification and gibberellic acid application) on time to germination. Seed
traits, phylogeny, and seed pretreatments all affected time to germination. Of
all traits tested, variables related to seed shape (height and shape variance)
best predicted germination response, with high-variance (i.e., pointier and
narrower) seeds germinating faster. Phylogenetic position (the location of
species on the phylogenetic tree relative to other tested species) was also an
important predictor of germination response, that is, closely related species
showed similar patterns in time to germination. This was true despite the fact
that all measured seed traits showed phylogenetic signal, therefore phylogeny
provided residual information that was not already captured by measured seed
traits. Seed traits, phylogenetic position, and germination pretreatments were
important predictors of germination response for a suite of species commonly used
in grassland restoration. Shape traits were especially important, while mass,
often the only seed trait used in studies of community assembly, was not a strong
predictor of germination timing. These findings illustrate the ecological
importance of seed traits that are rarely incorporated into functional studies of
plant communities. This information can also be used to advance restoration
practice by guiding restoration planning and seed mix design.
PMID- 29938074
TI - Guano exposed: Impact of aerobic conditions on bat fecal microbiota.
AB - Bats and their associated guano microbiota provide important terrestrial and
subterranean ecosystem services and serve as a reservoir for a wide range of
epizootic and zoonotic diseases. Unfortunately, large-scale studies of bats and
their guano microbiotas are limited by the time and cost of sample collection,
which requires specially trained individuals to work at night to capture bats
when they are most active. Indirectly surveying bat gut microbiota through guano
deposits could be a more cost-effective alternative, but it must first be
established whether the postdefecation exposure to an aerobic environment has a
large impact on the guano microbial community. A number of recent studies on
mammalian feces have shown that the impact of aerobic exposure is highly species
specific; therefore, it is difficult to predict how exposure will affect the bat
guano microbiota without empirical data. In our study, we collected fresh guano
samples from 24 individuals of 10 bat species that are common throughout the arid
environments of the American southwest and subjected the samples to 0, 1, and 12
hr of exposure. The biodiversity decreased rapidly after the shift from an
anaerobic to an aerobic environment-much faster than previously reported in
mammalian species. However, the relative composition of the core guano microbiota
remained stable and, using highly sensitive targeted PCR methods, we found that
pathogens present in the original, non-exposed samples could still be recovered
after 12 hr of exposure. These results suggest that with careful sample analysis
protocols, a more efficient passive collection strategy is feasible; for example,
guano could be collected on tarps placed near the roost entrance. Such passive
collection methods would greatly reduce the cost of sample collection by allowing
more sites or roosts to be surveyed with a fraction of trained personnel, time,
and effort investments needed.
PMID- 29938075
TI - Quantifying natural seasonal variation in mutation parameters with mutation
accumulation lines.
AB - Mutations create novel genetic variants, but their contribution to variation in
fitness and other phenotypes may depend on environmental conditions. Furthermore,
natural environments may be highly heterogeneous. We assessed phenotypes
associated with survival and reproductive success in over 30,000 plants
representing 100 mutation accumulation lines of Arabidopsis thaliana across four
temporal environments at a single field site. In each of the four assays,
environmental variance was substantially larger than mutational variance. For
some traits, whether mutational variance was significantly varied between
seasons. The founder genotype had mean trait values near the mean of the
distribution of the mutation accumulation lines in all field experiments. New
mutations also contributed more phenotypic variation than would be predicted,
given phenotypic and sequence-level divergence among natural populations of A.
thaliana. The combination of large environmental variance with a mean effect of
mutation near zero suggests that mutations could contribute substantially to
standing genetic variation.
PMID- 29938076
TI - Canopy bird assemblages are less influenced by habitat age and isolation than
understory bird assemblages in Neotropical secondary forest.
AB - Secondary forest habitats are increasingly recognized for their potential to
conserve biodiversity in the tropics. However, the development of faunal
assemblages in secondary forest systems varies according to habitat quality and
species-specific traits. In this study, we predicted that the recovery of bird
assemblages is dependent on secondary forest age and level of isolation, the
forest stratum examined, and the species' traits of feeding guild and body mass.
This study was undertaken in secondary forests in central Panama; spanning a
chronosequence of 60-, 90-, and 120-year-old forests, and in neighboring old
growth forest. To give equal attention to all forest strata, we employed a novel
method that paired simultaneous surveys in canopy and understory. This survey
method provides a more nuanced picture than ground-based studies, which are
biased toward understory assemblages. Bird reassembly varied according to both
habitat age and isolation, although it was challenging to separate these effects,
as the older sites were also more isolated than the younger sites. In
combination, habitat age and isolation impacted understory birds more than canopy
dwelling birds. Proportions of dietary guilds did not vary with habitat age, but
were significantly different between strata. Body mass distributions were similar
across forest ages for small-bodied birds, but older forest supported more large
bodied birds, probably due to control of poaching at these sites. Canopy
assemblages were characterized by higher species richness, and greater variation
in both dietary breadth and body mass, relative to understory assemblages. The
results highlight that secondary forests may offer critical refugia for many bird
species, particularly specialist canopy-dwellers. However, understory bird
species may be less able to adapt to novel and isolated habitats and should be
the focus of conservation efforts encouraging bird colonization of secondary
forests.
PMID- 29938077
TI - A land classification protocol for pollinator ecology research: An urbanization
case study.
AB - Land-use change is one of the most important drivers of widespread declines in
pollinator populations. Comprehensive quantitative methods for land
classification are critical to understanding these effects, but co-option of
existing human-focussed land classifications is often inappropriate for
pollinator research. Here, we present a flexible GIS-based land classification
protocol for pollinator research using a bottom-up approach driven by reference
to pollinator ecology, with urbanization as a case study. Our multistep method
involves manually generating land cover maps at multiple biologically relevant
radii surrounding study sites using GIS, with a focus on identifying land cover
types that have a specific relevance to pollinators. This is followed by a three
step refinement process using statistical tools: (i) definition of land-use
categories, (ii) principal components analysis on the categories, and (iii)
cluster analysis to generate a categorical land-use variable for use in
subsequent analysis. Model selection is then used to determine the appropriate
spatial scale for analysis. We demonstrate an application of our protocol using a
case study of 38 sites across a gradient of urbanization in South-East England.
In our case study, the land classification generated a categorical land-use
variable at each of four radii based on the clustering of sites with different
degrees of urbanization, open land, and flower-rich habitat. Studies of land-use
effects on pollinators have historically employed a wide array of land
classification techniques from descriptive and qualitative to complex and
quantitative. We suggest that land-use studies in pollinator ecology should
broadly adopt GIS-based multistep land classification techniques to enable robust
analysis and aid comparative research. Our protocol offers a customizable
approach that combines specific relevance to pollinator research with the
potential for application to a wide range of ecological questions, including
agroecological studies of pest control.
PMID- 29938078
TI - How to map forest structure from aircraft, one tree at a time.
AB - Forest structure is strongly related to forest ecology, and it is a key parameter
to understand ecosystem processes and services. Airborne laser scanning (ALS) is
becoming an important tool in environmental mapping. It is increasingly common to
collect ALS data at high enough point density to recognize individual tree crowns
(ITCs) allowing analyses to move beyond classical stand-level approaches. In this
study, an effective and simple method to map ITCs, and their stem diameter and
aboveground biomass (AGB) is presented. ALS data were used to delineate ITCs and
to extract ITCs' height and crown diameter; then, using newly developed
allometries, the ITCs' diameter at breast height (DBH) and AGB were predicted.
Gini coefficient of DBHs was also predicted and mapped aggregating ITCs
predictions. Two datasets from spruce dominated temperate forests were
considered: one was used to develop the allometric models, while the second was
used to validate the methodology. The proposed approach provides accurate
predictions of individual DBH and AGB (R2 = .85 and .78, respectively) and of
tree size distributions. The proposed method had a higher generalization ability
compared to a standard area-based method, in particular for the prediction of the
Gini coefficient of DBHs. The delineation method used detected more than 50% of
the trees with DBH >10 cm. The detection rate was particularly low for trees with
DBH below 10 cm, but they represent a small amount of the total biomass. The Gini
coefficient of the DBH distribution was predicted at plot level with R2 = .46.
The approach described in this work, easy applicable in different forested areas,
is an important development of the traditional area-based remote sensing tools
and can be applied for more detailed analysis of forest ecology and dynamics.
PMID- 29938079
TI - Discovering variation of secondary metabolite diversity and its relationship with
disease resistance in Cornus florida L.
AB - Understanding intraspecific relationships between genetic and functional
diversity is a major goal in the field of evolutionary biology and is important
for conserving biodiversity. Linking intraspecific molecular patterns of plants
to ecological pressures and trait variation remains difficult due to environment
driven plasticity. Next-generation sequencing, untargeted liquid chromatography
mass spectrometry (LC-MS) profiling, and interdisciplinary approaches integrating
population genomics, metabolomics, and community ecology permit novel strategies
to tackle this problem. We analyzed six natural populations of the disease
threatened Cornus florida L. from distinct ecological regions using genotype-by
sequencing markers and LC-MS-based untargeted metabolite profiling. We tested the
hypothesis that higher genetic diversity in C. florida yielded higher chemical
diversity and less disease susceptibility (screening hypothesis), and we also
determined whether genetically similar subpopulations were similar in chemical
composition. Most importantly, we identified metabolites that were associated
with candidate loci or were predictive biomarkers of healthy or diseased plants
after controlling for environment. Subpopulation clustering patterns based on
genetic or chemical distances were largely congruent. While differences in
genetic diversity were small among subpopulations, we did observe notable
similarities in patterns between subpopulation averages of rarefied-allelic and
chemical richness. More specifically, we found that the most abundant compound of
a correlated group of putative terpenoid glycosides and derivatives was
correlated with tree health when considering chemodiversity. Random forest
biomarker and genomewide association tests suggested that this putative iridoid
glucoside and other closely associated chemical features were correlated to SNPs
under selection.
PMID- 29938080
TI - The puzzling phylogeography of the haplochromine cichlid fish Astatotilapia
burtoni.
AB - Astatotilapia burtoni is a member of the "modern haplochromines," the most
species-rich lineage within the family of cichlid fishes. Although the species
has been in use as research model in various fields of research since almost
seven decades, including developmental biology, neurobiology, genetics and
genomics, and behavioral biology, little is known about its spatial distribution
and phylogeography. Here, we examine the population structure and phylogeographic
history of A. burtoni throughout its entire distribution range in the Lake
Tanganyika basin. In addition, we include several A. burtoni laboratory strains
to trace back their origin from wild populations. To this end, we reconstruct
phylogenetic relationships based on sequences of the mitochondrial DNA (mtDNA)
control region (d-loop) as well as thousands of genomewide single nucleotide
polymorphisms (SNPs) derived from restriction-associated DNA sequencing. Our
analyses reveal high population structure and deep divergence among several
lineages, however, with discordant nuclear and mtDNA phylogenetic inferences.
Whereas the SNP-based phylogenetic hypothesis uncovers an unexpectedly deep split
in A. burtoni, separating the populations in the southern part of the Lake
Tanganyika basin from those in the northern part, analyses of the mtDNA control
region suggest deep divergence between populations from the southwestern
shoreline and populations from the northern and southeastern shorelines of Lake
Tanganyika. This phylogeographic pattern and mitochondrial haplotype sharing
between populations from the very North and the very South of Lake Tanganyika can
only partly be explained by introgression linked to lake-level fluctuations
leading to past contact zones between otherwise isolated populations and large
scale migration events.
PMID- 29938081
TI - Assessment of a livestock GPS collar based on an open-source datalogger informs
best practices for logging intensity.
AB - Ecologists have used Global Positioning Systems (GPS) to track animals for 30
years. Issues today include logging frequency and precision in estimating space
use and travel distances, as well as battery life and cost. We developed a low
cost (~US$125), open-source GPS datalogger based on Arduino. To test the system,
we collected positions at 20-s intervals for several 1-week durations from cattle
and sheep on rangeland in North Dakota. We tested two questions of broad interest
to ecologists who use GPS collars to track animal movements: (1) How closely do
collared animals cluster in their herd? (2) How well do different logging
patterns estimate patch occupancy and total daily distance traveled? Tested
logging patterns included regular logging (one position every 5 or 10 min), and
burst logging (positions recorded at 20-s intervals for 5 or 10 min per hour
followed by a sleep period). Collared sheep within the same pasture spent 75% of
daytime periods within 51 m of each other (mean = 42 m); collared cattle were
within 111 m (mean = 76 m). In our comparison of how well different logging
patterns estimate space use versus constant logging, the proportion of positions
recorded in 1- and 16-ha patches differed by 2%-3% for burst logging and 1% for
regular logging. Although all logging patterns underestimated total daily
distance traveled, underestimations were corrected by multiplying estimations by
regression coefficients estimated by maximum likelihood. Burst logging can extend
battery life by a factor of 7. We conclude that a minimum of two collars
programmed with burst logging robustly estimate patch use and spatial
distribution of grazing livestock herds. Research questions that require
accurately estimating travel of individual animals, however, are probably best
addressed with regular logging intervals and will thus have greater battery
demands than spatial occupancy questions across all GPS datalogger systems.
PMID- 29938082
TI - Different patterns of colonization of Oxalis alpina in the Sky Islands of the
Sonoran desert via pollen and seed flow.
AB - Historical factors such as climatic oscillations during the Pleistocene epoch
have dramatically impacted species distributions. Studies of the patterns of
genetic structure in angiosperm species using molecular markers with different
modes of inheritance contribute to a better understanding of potential
differences in colonization and patterns of gene flow via pollen and seeds. These
markers may also provide insights into the evolution of reproductive systems in
plants. Oxalis alpina is a tetraploid, herbaceous species inhabiting the Sky
Island region of the southwestern United States and northern Mexico. Our main
objective in this study was to analyze the influence of climatic oscillations on
the genetic structure of O. alpina and the impact of these oscillations on the
evolutionary transition from tristylous to distylous reproductive systems. We
used microsatellite markers and compared our results to a previous study using
chloroplast genetic markers. The phylogeographic structure inferred by both
markers was different, suggesting that intrinsic characteristics including the
pollination system and seed dispersal have influenced patterns of gene flow.
Microsatellites exhibited low genetic structure, showed no significant
association between geographic and genetic distances, and all individual
genotypes were assigned to two main groups. In contrast, chloroplast markers
exhibited a strong association between geographic and genetic distance, had
higher levels of genetic differentiation, and were assigned to five groups. Both
types of DNA markers showed evidence of a northward expansion as a consequence of
climate warming occurring in the last 10,000 years. The data from both types of
markers support the hypothesis for several independent transitions from tristyly
to distyly.
PMID- 29938083
TI - Reproductive ecology of interior least tern and piping plover in relation to
Platte River hydrology and sandbar dynamics.
AB - In a recent study, Farnsworth et al. (2017) used distributions of nest initiation
dates drawn mostly from human-created, off-channel habitats and a model of
emergent sandbar habitat to evaluate the hypothesis that least terns (Sternula
antillarum) and piping plovers (Charadrius melodus) are physiologically adapted
to initiate nests concurrent with the cessation of spring river flow rises on two
sections of the Platte River, Nebraska. The study by Farnsworth et al. (2017) has
several shortcomings which bring into question the authors' principal assertion
that interior least tern and piping plovers are not adapted to occupying and
nesting on river sandbars on the Platte River system. We identify these
shortcomings and provide information, which, we suggest, would change their
conclusions if incorporated. Linked Article: https://doi.org/10.1002/ece3.4097.
PMID- 29938084
TI - Reproductive ecology of interior least tern and piping plover in relation to
Platte river hydrology and sandbar dynamics: Response to the letter to the
editor.
AB - This is a response to the Alexander, Jorgensen, and Bomberger-Brown (Ecology and
Evolution, XX, 2018, XX; hereafter, AJB) Letter to the Editor critiquing
Farnsworth et al. (Ecology and Evolution, 7, 2017, 3579; hereafter, our study),
which investigates the reproductive ecology of interior least terns and piping
plover in relation to Platte River hydrology and sandbar dynamics. Herein, we
address each of AJBs' technical arguments, demonstrating that our technical
approach and model assumptions were reasonable and provide a conservatively high
estimate of the potential for reproductive success when compared to observed nest
inundation events. We conclude with a description of the realities faced by the
Platte River Recovery Implementation Program (PRRIP) as we integrate learning to
adjust management actions. Linked Article: https://doi.org/10.1002/ece3.4109.
PMID- 29938085
TI - Insights from modeling studies on how climate change affects invasive alien
species geography.
AB - Climate change and biological invasions are threatening biodiversity and
ecosystem services worldwide. It has now been widely acknowledged that climate
change will affect biological invasions. A large number of studies have
investigated predicted shifts and other changes in the geographic ranges of
invasive alien species related to climate change using modeling approaches. Yet
these studies have provided contradictory evidence, and no consensus has been
reached. We conducted a systematic review of 423 modeling case studies included
in 71 publications that have examined the predicted effects of climate change on
those species. We differentiate the approaches used in these studies and
synthesize their main results. Our results reaffirm the major role of climate
change as a driver of invasive alien species distribution in the future. We found
biases in the literature both regarding the taxa, toward plants and
invertebrates, and the areas of the planet investigated. Despite these biases, we
found for the plants and vertebrates studied that climate change will more
frequently contribute to a decrease in species range size than an increase in the
overall area occupied. This is largely due to oceans preventing terrestrial
invaders from spreading poleward. In contrast, we found that the ranges of
invertebrates and pathogens studied are more likely to increase following climate
change. An important caveat to these findings is that researchers have rarely
considered the effects of climate change on transport, introduction success, or
the resulting impacts. We recommend closing these research gaps, and propose
additional avenues for future investigations, as well as opportunities and
challenges for managing invasions under climate change.
PMID- 29938086
TI - Genetic differentiation of Rubus chamaemorus populations in the Czech Republic
and Norway after the last glacial period.
AB - The population structure of cloudberry (Rubus chamaemorus L.), collected from
Krkonose Mountains (the Czech Republic), continental Norway and Spitsbergen, was
examined using microsatellite analyses (SSR). Among 184 individuals, 162
different genotypes were identified. The overall unbiased gene diversity was high
( h^=0.463 ). A high level of genetic differentiation among populations (FST =
0.45; p < .01) indicated restricted gene flow between populations. Using a
Bayesian approach, six clusters were found which represented the genetic
structure of the studied cloudberry populations. The value of correlation index
between genetic and geographical distances (r = .44) indicates that gene flow,
even over a long distance, could exist. An exact test of population
differentiation showed that Rubus chamaemorus populations from regions (Krkonose
Mountains, continental Norway and Spitsbergen) are differentiated although some
individuals within populations share common alleles even among regions. These
results were confirmed by AMOVA, where the highest level of diversity was found
within populations (70.8%). There was no difference between 87 pairs of
populations (18.7%) mostly within cloudberry populations from continental Norway
and from Spitsbergen. Based on obtained results, it is possible to conclude that
Czech and Norwegian cloudberry populations are undergoing differentiation, which
preserves unique allele compositions most likely from original populations during
the last glaciation period. This knowledge will be important for the creation and
continuation of in situ and ex situ conservation of cloudberry populations within
these areas.
PMID- 29938087
TI - Long-term regeneration of a tropical plant community after sand mining.
AB - Sandy coastal plant communities in tropical regions have been historically under
strong anthropic pressure. In Brazil, these systems shelter communities with
highly plastic plant species. However, the potential of these systems to
regenerate without human assistance after disturbances has hardly been examined.
We determined the natural regeneration of a coastal sandy plain vegetation
(restinga) in Brazil, 16 years after the end of sand removal. We inventoried 38
plots: 20 within a sand-mined site and 18 in an adjacent undisturbed site. We
expected lower diversity values in the sand-mined site compared to the
undisturbed site, but similar species composition between the two sites due to
the spatial proximity of the two sites and the high plasticity of restinga
species. Species were ranked using abundance and importance value index in both
sites, and comparisons were performed using Renyi entropy profiles, rarefaction
curves, principal component analysis, and redundancy analysis. Species
composition and dominant species differed markedly between the two sites.
Bromeliads and Clusia hilariana, well-known nurse plants, dominated the
undisturbed site but were almost absent in the regenerating site. Species
richness did not differ between both sites, but diversity was higher in the
undisturbed site. Within-site composition differences in the mined area were
associated with field characteristics. Interestingly, species classified as
subordinate or rare in the undisturbed site became dominants in the regenerating
site. These newer dominants in the sand-mined site are not those known as nurse
plants in other restingas, thus yielding strong implications for restoration.
PMID- 29938088
TI - The combination of arbuscular mycorrhizal fungi inoculation (Glomus versiforme)
and 28-homobrassinolide spraying intervals improves growth by enhancing
photosynthesis, nutrient absorption, and antioxidant system in cucumber (Cucumis
sativus L.) under salinity.
AB - Salinity is one of the major obstacles in the agriculture industry causing huge
losses in productivity. Several strategies such as plant growth regulators with
arbuscular mycorrhizal fungi (AMF) have been used to decrease the negative
effects of salt stress. In our experiment, 28-homobrassinolide (HBL) with
spraying intervals was combined with AMF (Glomus versiforme) in cucumber
cultivars Jinyou 1# (salt sensitive) and (Changchun mici, in short, CCMC, salt
tolerant) under NaCl (100 mmol/L). Studies have documented that the foliar
application of HBL and AMF colonization can enhance tolerance to plants under
stress conditions. However, the mechanism of the HBL spraying intervals after 15
and 30 days in combination with AMF in cucumber under salt stress is still
unknown. Our results revealed that the HBL spraying interval after 15 days in
combination with AMF resulted in improved growth, photosynthesis, and decreased
sodium toxicity under NaCl. Moreover, the antioxidant enzymes SOD (superoxide
dismutase; EC 1.15.1.1) and POD activity (peroxidase; EC 1.11.1.7) showed a
gradual increase after every 10 days, while the CAT (catalase; EC 1.11.1.6)
increased after 30 days of salt treatments in both cultivars. This research
suggests that the enhanced tolerance to salinity was mainly related to elevated
levels of antioxidant enzymes and lower uptake of Na+, which lowers the risk of
ion toxicity and decreases cell membrane damage.
PMID- 29938089
TI - Testing the effects of heterozygosity on growth rate plasticity in the seaweed
Gracilaria chilensis (Rhodophyta).
AB - Heterozygosity has been positively associated with fitness and population
survival. However, the relationship between heterozygosity and adaptive
phenotypic plasticity (i.e., plasticity which results in fitness homeostasis or
improvement in changing environments) is unclear and has been poorly explored in
seaweeds. In this study, we explored this relationship in the clonal red seaweed,
Gracilaria chilensis by conducting three growth rate plasticity experiments under
contrasting salinity conditions and by measuring heterozygosity with five
microsatellite DNA markers. Firstly, we compared growth rate plasticity between
the haploid and diploid phases. Secondly, we compared growth rate plasticity
between diploids with different numbers of heterozygous loci. Finally, we
compared growth rate plasticity between diploid plants from two populations that
are expected to exhibit significant differences in heterozygosity. We found that,
(i) diploids displayed a higher growth rate and lower growth rate plasticity than
haploids, (ii) diploids with a higher number of heterozygous loci displayed lower
growth rate plasticity than those exhibiting less heterozygosity, and (iii)
diploid sporophytes from the population with higher heterozygosity displayed
lower growth rate plasticity than those with lower heterozygosity. Accordingly,
this study suggests that heterozygosity is inversely related to growth rate
plasticity in G. chilensis. However, better genetic tools in seaweeds are
required for a more definitive conclusion on the relationship between
heterozygosity and phenotypic plasticity.
PMID- 29938090
TI - Predator-prey mass ratio drives microbial activity under dry conditions in
Sphagnum peatlands.
AB - Mid- to high-latitude peatlands are a major terrestrial carbon stock but become
carbon sources during droughts, which are increasingly frequent as a result of
climate warming. A critical question within this context is the sensitivity to
drought of peatland microbial food webs. Microbiota drive key ecological and
biogeochemical processes, but their response to drought is likely to impact these
processes. Peatland food webs have, however, been little studied, especially the
response of microbial predators. We studied the response of microbial predators
(testate amoebae, ciliates, rotifers, and nematodes) living in Sphagnum moss
carpet to droughts, and their influence on lower trophic levels and on related
microbial enzyme activity. We assessed the impact of reduced water availability
on microbial predators in two peatlands using experimental (Linje mire, Poland)
and natural (Forbonnet mire, France) water level gradients, reflecting a sudden
change in moisture regime (Linje), and a typically drier environment (Forbonnet).
The sensitivity of different microbial groups to drought was size dependent;
large sized microbiota such as testate amoebae declined most under dry conditions
(-41% in Forbonnet and -80% in Linje). These shifts caused a decrease in the
predator-prey mass ratio (PPMR). We related microbial enzymatic activity to PPMR;
we found that a decrease in PPMR can have divergent effects on microbial
enzymatic activity. In a community adapted to drier conditions, decreasing PPMR
stimulated microbial enzyme activity, while in extreme drought experiment, it
reduced microbial activity. These results suggest that microbial enzymatic
activity resulting from food web structure is optimal only within a certain range
of PPMR, and that different trophic mechanisms are involved in the response of
peatlands to droughts. Our findings confirm the importance of large microbial
consumers living at the surface of peatlands on the functioning of peatlands, and
illustrate their value as early warning indicators of change.
PMID- 29938091
TI - Consistent pollen nutritional intake drives bumble bee (Bombus impatiens) colony
growth and reproduction across different habitats.
AB - Foraging behavior is a critical adaptation by insects to obtain appropriate
nutrients from the environment for development and fitness. Bumble bees (Bombus
spp.) form annual colonies which must rapidly increase their worker populations
to support rearing reproductive individuals before the end of the season.
Therefore, colony growth and reproduction should be dependent on the quality and
quantity of pollen resources in the surrounding landscape. Our previous research
found that B. impatiens foraging preferences to different plant species were
shaped by pollen protein:lipid nutritional ratios (P:L), with foragers preferring
pollen species with a ~5:1 P:L ratio. In this study, we placed B. impatiens
colonies in three different habitats (forest, forest edge, and valley) to
determine whether pollen nutritional quality collected by the colonies differed
between areas that may differ in resource abundance and diversity. We found that
habitat did not influence the collected pollen nutritional quality, with colonies
in all three habitats collecting pollen averaging a 4:1 P:L ratio. Furthermore,
there was no difference in the nutritional quality of the pollen collected by
colonies that successfully reared reproductives and those that did not. We found
however, that "nutritional intake," calculated as the colony-level intake rate of
nutrient quantities (protein, lipid, and sugar), was strongly related to colony
growth and reproductive output. Therefore, we conclude that B. impatiens colony
performance is a function of the abundance of nutritionally appropriate floral
resources in the surrounding landscape. Because we did not comprehensively
evaluate the nutrition provided by the plant communities in each habitat, it
remains to be determined how B. impatiens polylectic foraging strategies helps
them select among the available pollen nutritional landscape in a variety of
plant communities to obtain a balance of key macronutrients.
PMID- 29938092
TI - When beggars are choosers-How nesting of a solitary bee is affected by temporal
dynamics of pollen plants in the landscape.
AB - Wild bees are declining in intensively farmed regions worldwide, threatening
pollination services to flowering crops and wild plants. To halt bee declines, it
is essential that conservation actions are based on a mechanistic understanding
of how bee species utilize landscapes. We aimed at teasing apart how foraging
resources in the landscape through the nesting season affected nesting and
reproduction of a solitary bee in a farmland region. We investigated how
availability of floral resources and potentially resource-rich habitats
surrounding nests affected nest provisioning and reproduction in the solitary
polylectic bee Osmia bicornis. The study was performed in 18 landscape sectors
dominated by agriculture, but varying in agricultural intensity in terms of
proportion of organic crop fields and seminatural permanent pastures. Pasture
rich sectors contained more oak (Quercus robur), which pollen analysis showed to
be favored forage in early season. More oaks <=100 m from nests led to higher
proportions of oak pollen in nest provisions and increased speed of nest
construction in early season, but this effect tapered off as flowering decreased.
Late-season pollen foraging was dominated by buttercup (Ranunculus spp.), common
in various noncrop habitats. Foraging trips were longer with more oaks and
increased further through the season. The opposite was found for buttercup. Oak
and buttercup interacted to explain the number of offspring; buttercup had a
positive effect only when the number of oaks was above the mean for the studied
sectors. The results show that quality of complex and pasture-rich landscapes for
O. bicornis depends on preserving existing and generating new oak trees. Lignose
plants are key early-season forage resources in agricultural landscapes.
Increasing habitat heterogeneity with trees and shrubs and promoting suitable
late-flowering forbs can benefit O. bicornis and other wild bees active in spring
and early summer, something which existing agri-environment schemes seldom
target.
PMID- 29938093
TI - Carbon allocation and competition maintain variation in plant root mutualisms.
AB - Plants engage in multiple root symbioses that offer varying degrees of benefit.
We asked how variation in partner quality persists using a resource-ratio model
of population growth. We considered the plant's ability to preferentially
allocate carbon to mutualists and competition for plant carbon between mutualist
and nonmutualist symbionts. We treated carbon as two nutritionally
interchangeable, but temporally separated, resources-carbon allocated
indiscriminately for the construction of the symbiosis, and carbon preferentially
allocated to the mutualist after symbiosis establishment and assessment. This
approach demonstrated that coexistence of mutualists and nonmutualists is
possible when fidelity of the plant to the mutualist and the cost of mutualism
mediate resource competition. Furthermore, it allowed us to trace symbiont
population dynamics given varying degrees of carbon allocation. Specifically,
coexistence occurs at intermediate levels of preferential allocation. Our
findings are consistent with previous empirical studies as well the application
of biological market theory to plantroot symbioses.
PMID- 29938094
TI - Following the water? Landscape-scale temporal changes in bat spatial distribution
in relation to Mediterranean summer drought.
AB - Understanding how the spatial distribution of ecological resources shapes
species' diversity and abundance in human-modified landscapes is a central theme
in conservation biology. However, studies often disregard that such patterns may
vary over time, thereby potentially missing critical environmental constraints to
species persistence. This may be particularly important in highly mobile species
such as bats, which are able to track temporal variations in spatial resource
distribution. Here we test the hypothesis that bats in Mediterranean landscapes
are strongly affected by the progressive reduction in water availability during
the seasonal summer drought. We analyzed the effects of landscape composition and
structure on bat diversity and activity, during pregnancy, lactation, and
postlactation periods, and identified the most influential variables within and
across periods. Water bodies showed the strongest positive effect on bats,
followed by riparian habitats and areas with steeper (>30%) slopes. However,
while during pregnancy, there were only small landscape effects, these increased
during lactation and postlactation, highlighting a progressively stronger
association with water habitats during the summer drought. The spatial projection
of habitat models showed that the landscape distribution of bat diversity and
activity hotspots changed markedly over time. During pregnancy, the spatial
pattern of hotspot distribution was weakly defined, while during lactation and
particularly postlactation, there was a concentration of hotspots along
permanently flowing watercourses. Our study highlights that permanently flowing
watercourses are critical for bat conservation in Mediterranean landscapes,
calling for measures to counteract their ongoing degradation due in particular to
climate change, water abstraction and damming. More generally, our study
underlines the importance of considering the temporal dimension in habitat
selection studies, without which there is the risk of overlooking the importance
of habitats that are key for species persistence only at certain times of the
year.
PMID- 29938095
TI - Altered spring phenology of North American freshwater turtles and the importance
of representative populations.
AB - Globally, populations of diverse taxa have altered phenology in response to
climate change. However, most research has focused on a single population of a
given taxon, which may be unrepresentative for comparative analyses, and few long
term studies of phenology in ectothermic amniotes have been published. We test
for climate-altered phenology using long-term studies (10-36 years) of nesting
behavior in 14 populations representing six genera of freshwater turtles
(Chelydra, Chrysemys, Kinosternon, Malaclemys, Sternotherus, and Trachemys).
Nesting season initiation occurs earlier in more recent years, with 11 of the
populations advancing phenology. The onset of nesting for nearly all populations
correlated well with temperatures during the month preceding nesting. Still,
certain populations of some species have not advanced phenology as might be
expected from global patterns of climate change. This collection of findings
suggests a proximate link between local climate and reproduction that is
potentially caused by variation in spring emergence from hibernation, ability to
process food, and thermoregulatory opportunities prior to nesting. However, even
though all species had populations with at least some evidence of phenological
advancement, geographic variation in phenology within and among turtle species
underscores the critical importance of representative data for accurate
comprehensive assessments of the biotic impacts of climate change.
PMID- 29938096
TI - Males, but not females, perform strategic mate searching movements between host
plants in a leaf beetle with scramble competition polygyny.
AB - Mate searching is assumed to be performed mostly by males, but when females
benefit from multiple mating or are under risk of failing to mate, they may also
perform mate searching. This is especially important in scramble competition
polygynies, in which mate searching is the main mechanism of mate competition.
Typically, more mobile individuals are expected to achieve higher mating success
because mobility increases their probability of finding mates. If we assume
individual movements are mainly explained by mate searching in scramble
competition polygynies, we can investigate searching strategies by asking when
individuals should leave their location and where they should go. We hypothesize
that individuals will leave their locations when mating opportunities are scarce
and will seek spatially close sites with better mating opportunities. We tested
these hypotheses for males and females of Leptinotarsa undecimlineata, a leaf
beetle with scramble competition polygyny in which both sexes are promiscuous.
Individuals mate and feed exclusively on Solanum plants, and thus, individual
movements can be described as switches between plants. Females were less likely
than males to leave isolated plants, and both males and females moved
preferentially to neighboring plants. Males were more likely to leave when the
local number of females was low, and the number of males was high. They moved to
plants with more females, a behavior consistent with a mate searching strategy.
Females were more likely to move to plants with fewer males and many females, a
behavior consistent with male harassment avoidance. Strategic movement is widely
considered in foraging context, but seldom in a mate searching context.
Considering that selection to minimize searching costs, maximize mating success,
and minimize harassment may be ubiquitous in nature, we argue that strategic
movements by mate searching individuals are likely to occur in many species.
PMID- 29938097
TI - A nuclear DNA barcode for eastern North American oaks and application to a study
of hybridization in an Arboretum setting.
AB - DNA barcoding has proved difficult in a number of woody plant genera, including
the ecologically important oak genus Quercus. In this study, we utilized
restrictionsite-associated DNA sequencing (RAD-seq) to develop an economical
single nucleotide polymorphism (SNP) DNA barcoding system that suffices to
distinguish eight common, sympatric eastern North American white oak species. Two
de novo clustering pipelines, PyRAD and Stacks, were used in combination with
postclustering bioinformatic tools to generate a list of 291 potential SNPs, 80
of which were included in a barcoding toolkit that is easily implemented using
MassARRAY mass spectrometry technology. As a proof-of-concept, we used the
genotyping toolkit to infer potential hybridization between North American white
oaks transplanted outside of their native range (Q. michauxii, Q. montana, Q
muehlenbergii/Q. prinoides, and Q. stellata) into a horticultural collection
surrounded by natural forests of locally native trees (Q. alba and Q. macrocarpa)
in the living collection at The Morton Arboretum (Lisle, IL, USA). Phylogenetic
and clustering analyses suggested low rates of hybridization between cultivated
and native species, with the exception of one Q. michauxii mother tree, the
acorns of which exhibited high admixture from either Q. alba or Q. stellata and
Q. macrocarpa, and a hybrid between Q. stellata that appears to have backcrossed
almost exclusively to Q. alba. Together, RAD-seq and MassARRAY technologies allow
for efficient development and implementation of a multispecies barcode for one of
the more challenging forest tree genera.
PMID- 29938098
TI - The indestructible insect: Velvet ants from across the United States avoid
predation by representatives from all major tetrapod clades.
AB - Velvet ants are a group of parasitic wasps that are well known for a suite of
defensive adaptations including bright coloration and a formidable sting. While
these adaptations are presumed to function in antipredator defense, observations
between potential predators and this group are lacking. We conducted a series of
experiments to determine the risk of velvet ants to a host of potential predators
including amphibians, reptiles, birds, and small mammals. Velvet ants from across
the United States were tested with predator's representative of the velvet ants
native range. All interactions between lizards, free-ranging birds, and a mole
resulted in the velvet ants survival, and ultimate avoidance by the predator. Two
shrews did injure a velvet ant, but this occurred only after multiple failed
attacks. The only predator to successfully consume a velvet ant was a single
American toad (Anaxyrus americanus). These results indicate that the suite of
defenses possessed by velvet ants, including aposematic coloration,
stridulations, a chemical alarm signal, a hard exoskeleton, and powerful sting
are effective defenses against potential predators. Female velvet ants appear to
be nearly impervious to predation by many species whose diet is heavily derived
of invertebrate prey.
PMID- 29938099
TI - Woodland caribou habitat selection patterns in relation to predation risk and
forage abundance depend on reproductive state.
AB - The ideal free distribution assumes that animals select habitats that are
beneficial to their fitness. When the needs of dependent offspring differ from
those of the parent, ideal habitat selection patterns could vary with the
presence or absence of offspring. We test whether habitat selection depends on
reproductive state due to top-down or bottom-up influences on the fitness of
woodland caribou (Rangifer tarandus caribou), a threatened, wide-ranging
herbivore. We combined established methods of fitting resource and step selection
functions derived from locations of collared animals in Ontario with newer
techniques, including identifying calf status from video collar footage and
seasonal habitat selection analysis through latent selection difference
functions. We found that females with calves avoided predation risk and proximity
to roads more strongly than females without calves within their seasonal ranges.
At the local scale, females with calves avoided predation more strongly than
females without calves. Females with calves increased predation avoidance but not
selection for food availability upon calving, whereas females without calves
increased selection for food availability across the same season. These
behavioral responses suggest that habitat selection by woodland caribou is
influenced by reproductive state, such that females with calves at heel use
habitat selection to offset the increased vulnerability of their offspring to
predation risk.
PMID- 29938101
TI - Three-dimensional digitization of the arid land plant Haloxylon ammodendron using
a consumer-grade camera.
AB - Plant structural parameters are important for ecological studies and for
monitoring the environment. Terrestrial laser scanning has become a widely
accepted technique for acquiring accurate high-density three-dimensional
information about plant surfaces; however, this instrument is expensive,
technically challenging to operate, heavy, and difficult to transport to hard-to
reach areas such as dense forests and undeveloped areas without easy vehicle
access. Using Haloxylon ammodendron, a plant widely distributed in arid lands, as
an example, we used a consumer-grade handheld camera to take a series of
overlapping images of this plant. Computer vision and photogrammetric software
were used to reconstruct highly detailed three-dimensional data of the plant
surface. This surface data was compared to the point cloud of the plant acquired
from concomitant terrestrial laser scanning. We demonstrated that the accuracy
and degree of completeness of the image-derived point clouds are comparable to
that of laser scanning. Plant structural parameters (such as tree height and
crown width) and three-dimensional models extracted from the point clouds also
agree well with a relative difference of less than 5%. Our case study shows that
a common camera and image processing software can be an affordable, highly
portable, and viable option for acquiring accurate and detailed high-density and
high-resolution three-dimensional information about plant structure in the
environment. This digitization technique can record the plant and its surrounding
environment effectively and efficiently, and it can be applied to many ecological
fields and studies.
PMID- 29938102
TI - Effects of experimental N addition on plant diversity in an old-growth temperate
forest.
AB - Temperate forest ecosystems have experienced mounting negative effects due to
increasing levels of nitrogen (N) deposition. We examined the effects of
experimental N addition on plant diversity in an old-growth temperate forest to
test the following hypothesis: Long-term excessive N addition decreases plant
diversity by affecting the growth of plants, which results from changes in the
soil nutrient content and a decrease in the soil pH in temperate forests.
Experimental N additions were administered at the following levels since 2008:
control (0 kg N ha-1 year-1), low N (30 kg N ha-1 year-1), medium N (60 kg N ha-1
year-1), and high N (120 kg N ha-1 year-1). Additionally, plant diversity was
studied from 2014 to 2016. The results showed that the experimental N additions
had significant effects on plant diversity and soil properties in an old-growth
temperate forest. The high-N treatment decreased the density, cover, and
diversity of understory plants, and some herbs even appeared to undergo premature
aging, whereas the species diversity of herbs and ferns in the low-N treatment
plots showed a slight increasing tendency. This may have been because the old
growth temperate forest is an N-limited ecosystem, so the moderate N input did
not show a large influence on plant diversity. However, the long-term high-N
treatment ultimately reduced plant diversity by changing the soil nutrient
contents, decreasing the pH values, and damaging plant growth. Our results
suggested that the long-term excessive N addition negatively affected the forest
ecosystem in an N-limited temperature forest.
PMID- 29938100
TI - Genotyping by sequencing reveals contrasting patterns of population structure,
ecologically mediated divergence, and long-distance dispersal in North American
palms.
AB - Comparative studies can provide powerful insights into processes that affect
population divergence and thereby help to elucidate the mechanisms by which
contemporary populations may respond to environmental change. Furthermore,
approaches such as genotyping by sequencing (GBS) provide unprecedented power for
resolving genetic differences among species and populations. We therefore used
GBS to provide a genomewide perspective on the comparative population structure
of two palm genera, Washingtonia and Brahea, on the Baja California peninsula, a
region of high landscape and ecological complexity. First, we used phylogenetic
analysis to address taxonomic uncertainties among five currently recognized
species. We resolved three main clades, the first corresponding to W. robusta and
W. filifera, the second to B. brandegeei and B. armata, and the third to B.
edulis from Guadalupe Island. Focusing on the first two clades, we then delved
deeper by investigating the underlying population structure. Striking differences
were found, with GBS uncovering four distinct Washingtonia populations and
identifying a suite of loci associated with temperature, consistent with
ecologically mediated divergence. By contrast, individual mountain ranges could
be resolved in Brahea and few loci were associated with environmental variables,
implying a more prominent role of neutral divergence. Finally, evidence was found
for long-distance dispersal events in Washingtonia but not Brahea, in line with
knowledge of the dispersal mechanisms of these palms including the possibility of
human-mediated dispersal. Overall, our study demonstrates the power of GBS
together with a comparative approach to elucidate markedly different patterns of
genomewide divergence mediated by multiple effectors.
PMID- 29938103
TI - Density-dependent and density-independent drivers of population change in Barton
Springs salamanders.
AB - Understanding population change is essential for conservation of imperiled
species, such as amphibians. Worldwide amphibian declines have provided an
impetus for investigating their population dynamics, which can involve both
extrinsic (density-independent) and intrinsic (density-dependent) drivers acting
differentially across multiple life stages or age classes. In this study, we
examined the population dynamics of the endangered Barton Springs Salamander
(Eurycea sosorum) using data from a long-term monitoring program. We were
interested in understanding both the potential environmental drivers (density
independent factors) and demographic factors (interactions among size classes,
negative density dependence) to better inform conservation and management
activities. We used data from three different monitoring regimes and multivariate
autoregressive state-space models to quantify environmental effects (seasonality,
discharge, algae, and sediment cover), intraspecific interactions among three
size classes, and intra-class density dependence. Results from our primary data
set revealed similar patterns among sites and size classes and were corroborated
by our out-of-sample data. Cross-correlation analysis showed juvenile abundance
was most strongly correlated with a 9-month lag in aquifer discharge, which we
suspect is related to inputs of organic carbon into the aquifer. However,
sedimentation limited juvenile abundance at the surface, emphasizing the
importance of continued sediment management. Recruitment from juveniles to the
sub-adult size class was evident, but negative density-dependent feedback
ultimately regulated each size class. Negative density dependence may be an
encouraging sign for the conservation of E. sosorum because populations that can
reach carrying capacity are less likely to go extinct compared to unregulated
populations far below their carrying capacity. However, periodic population
declines coupled with apparent migration into the aquifer complicate assessments
of species status. Although both density-dependent and density-independent
drivers of population change are not always apparent in time series of animal
populations, both have important implications for conservation and management of
E. sosorum.
PMID- 29938104
TI - Edge effects in fire-prone landscapes: Ecological importance and implications for
fauna.
AB - Edges are ecologically important environmental features and have been well
researched in agricultural and urban landscapes. However, little work has been
conducted in flammable ecosystems where spatially and temporally dynamic fire
edges are expected to influence important processes such as recolonization of
burnt areas and landscape connectivity. We review the literature on fire, fauna,
and edge effects to summarize current knowledge of faunal responses to fire edges
and identify knowledge gaps. We then develop a conceptual model to predict faunal
responses to fire edges and present an agenda for future research. Faunal
abundance at fire edges changes over time, but patterns depend on species traits
and resource availability. Responses are also influenced by edge architecture
(e.g., size and shape), site and landscape context, and spatial scale. However,
data are limited and the influence of fire edges on both local abundance and
regional distributions of fauna is largely unknown. In our conceptual model,
biophysical properties interact with the fire regime (e.g., patchiness,
frequency) to influence edge architecture. Edge architecture and species traits
influence edge permeability, which is linked to important processes such as
movement, resource selection, and species interactions. Predicting the effect of
fire edges on fauna is challenging, but important for biodiversity conservation
in flammable landscapes. Our conceptual model combines several drivers of faunal
fire responses (biophysical properties, regime attributes, species traits) and
will therefore lead to improved predictions. Future research is needed to
understand fire as an agent of edge creation; the spatio-temporal flux of fire
edges across landscapes; and the effect of fire edges on faunal movement,
resource selection, and biotic interactions. To aid the incorporation of new data
into our predictive framework, our model has been designed as a Bayesian Network,
a statistical tool capable of analyzing complex environmental relationships,
dealing with data gaps, and generating testable hypotheses.
PMID- 29910945
TI - Finding indexes of spontaneous brain-to-brain communications when looking for a
cause of the similarity of qualia assumed across individuals.
AB - Qualia, the individual instances of subjective conscious experience, are private
events. However, in everyday life, we assume qualia of others and their
perceptual worlds, to be similar to ours. One way this similarity is possible is
if qualia of others somehow contribute to the production of qualia by our own
brain and vice versa. To test this hypothesis, we focused on the mean voltages of
event-related potentials (ERPs) in the time-window of the P600 component, whose
amplitude correlates positively with conscious awareness. These ERPs were
elicited by stimuli of the international affective picture system in 16 pairs of
friends, siblings or couples going side by side through hyperscanning without
having to interact. Each of the 32 members of these 16 pairs faced one half of
the screen and could not see what the other member was presented with on the
other half. One stimulus occurred on each half simultaneously. The sameness of
these stimulus pairs was manipulated as well as the participants' belief in that
sameness by telling subjects' pairs that they were going to be presented with the
same stimuli in two blocks and with different ones in the two others. In the P600
time window, belief, and thus social cognition, was found to have an effect on
ERPs only at left anterior electrode sites. In contrast, ERPs were more positive
at all electrode subsets for stimulus pairs that were inconsistent with the
belief than for those that were consistent. In the N400 time window, at frontal
electrode sites, ERPs were again more positive for inconsistent than for
consistent stimuli. As participants had no way to see the stimulus their partner
was presented with, and thus no way to detect inconsistence, we proposed that
these data could support the existence of spontaneous brain-to-brain
communications. Such communications might provide a research avenue when trying
to explain the similarity of qualia across individuals, which is assumed in
virtually all instants of every day life.
PMID- 29938105
TI - Current challenges in distinguishing climatic and anthropogenic contributions to
alpine grassland variation on the Tibetan Plateau.
AB - Quantifying the impact of climate change and human activities on grassland
dynamics is an essential step for developing sustainable grassland ecosystem
management strategies. However, the direction and magnitude of climate change and
human activities in driving alpine grassland dynamic over the Tibetan Plateau
remain under debates. Here, we systematically reviewed the relevant studies on
the methods, main conclusions, and causes for the inconsistency in distinguishing
the respective contribution of climatic and anthropogenic forces to alpine
grassland dynamic. Both manipulative experiments and traditional statistical
analysis show that climate warming increase biomass in alpine meadows and
decrease in alpine steppes, while both alpine steppes and meadows benefit from an
increase in precipitation or soil moisture. Overgrazing is a major factor for the
degradation of alpine grassland in local areas with high level of human activity
intensity. However, across the entire Tibetan Plateau and its subregions, four
views characterize the remaining controversies: alpine grassland changes are
primarily due to (1) climatic force, (2) nonclimatic force, (3) combination of
anthropogenic and climatic force, or (4) alternation of anthropogenic and
climatic force. Furthermore, these views also show spatial inconsistencies.
Differences on the source and quality of remote sensing products, the structure
and parameter of models, and overlooking the spatiotemporal heterogeneity of
human activity intensity contribute to current disagreements. In this review, we
highlight the necessity for taking the spatiotemporal heterogeneity of human
activity intensity into account in the models of attribution assessment, and the
importance for accurate validation of climatic and anthropogenic contribution to
alpine grassland variation at multiple scales for future studies.
PMID- 29910945
TI - Looking for effects of qualia on event-related brain potentials of close others
in search for a cause of the similarity of qualia assumed across individuals.
AB - Qualia, the individual instances of subjective conscious experience, are private
events. However, in everyday life, we assume qualia of others and their
perceptual worlds, to be similar to ours. One way this similarity is possible is
if qualia of others somehow contribute to the production of qualia by our own
brain and vice versa. To test this hypothesis, we focused on the mean voltages of
event-related potentials (ERPs) in the time-window of the P600 component, whose
amplitude correlates positively with conscious awareness. These ERPs were
elicited by images of the international affective picture system in 16 pairs of
friends, siblings or couples going side by side through hyperscanning without
having to interact. Each of the 32 members of these 16 pairs faced one half of
the screen and could not see what the other member was presented with on the
other half. One stimulus occurred on each half simultaneously. The sameness of
these stimulus pairs was manipulated as well as the participants' belief in that
sameness by telling subjects' pairs that they were going to be presented with the
same stimuli in two blocks and with different ones in the two others. ERPs were
more positive at all electrode subsets for stimulus pairs that were inconsistent
with the belief than for those that were consistent. In the N400 time window, at
frontal electrode sites, ERPs were again more positive for inconsistent than for
consistent stimuli. As participants had no way to see the stimulus their partner
was presented with and thus no way to detect inconsistence, these data might
reveal an impact of the qualia of a person on the brain activity of another. Such
impact could provide a research avenue when trying to explain the similarity of
qualia across individuals.
PMID- 29938108
TI - A biochemical logarithmic sensor with broad dynamic range.
AB - Sensory perception often scales logarithmically with the input level. Similarly,
the output response of biochemical systems sometimes scales logarithmically with
the input signal that drives the system. How biochemical systems achieve
logarithmic sensing remains an open puzzle. This article shows how a biochemical
logarithmic sensor can be constructed from the most basic principles of chemical
reactions. Assuming that reactions follow the classic Michaelis-Menton kinetics
of mass action or the more generalized and commonly observed Hill equation
response, the summed output of several simple reactions with different
sensitivities to the input will often give an aggregate output response that
logarithmically transforms the input. The logarithmic response is robust to
stochastic fluctuations in parameter values. This model emphasizes the simplicity
and robustness by which aggregate chemical circuits composed of sloppy components
can achieve precise response characteristics. Both natural and synthetic designs
gain from the power of this aggregate approach.
PMID- 29938109
TI - Finding the right connection: what makes a successful decision support system?
AB - Farmers require evidence-based guidance to make optimal decisions, enabling them
to reduce costs by increasing the efficiency of input use. We discuss how
decision support systems could be improved and made more useful for the farmer.
PMID- 29938111
TI - "An example for corporate social responsibility": British American Tobacco's
response to criticism of its Myanmar subsidiary, 1999-2003.
AB - In 2013, British American Tobacco (BAT) returned to Myanmar a decade after it had
left the country under pressure from civil society, international organizations,
and the government of the United Kingdom. The company's involvement in a joint
venture with an investment branch of the country's military government between
1999 and 2003 resulted in intense scrutiny and criticism based on the military's
record of human rights abuses. BAT argued that corporations could not be held
accountable for actions of governments in countries in which it operated, and
that its presence in Myanmar contributed to economic and social development. It
also maintained that its Myanmar subsidiary provided a model of responsible
business conduct. The controversy that surrounded BAT's Myanmar subsidiary
between 1999 and 2003 has increasing relevance to the current situation in
Myanmar, and potential implications for foreign corporations operating in the
country.
PMID- 29938110
TI - Construction of a network describing asparagine metabolism in plants and its
application to the identification of genes affecting asparagine metabolism in
wheat under drought and nutritional stress.
AB - A detailed network describing asparagine metabolism in plants was constructed
using published data from Arabidopsis (Arabidopsis thaliana) maize (Zea mays),
wheat (Triticum aestivum), pea (Pisum sativum), soybean (Glycine max), lupin
(Lupus albus), and other species, including animals. Asparagine synthesis and
degradation is a major part of amino acid and nitrogen metabolism in plants. The
complexity of its metabolism, including limiting and regulatory factors, was
represented in a logical sequence in a pathway diagram built using yED graph
editor software. The network was used with a Unique Network Identification
Pipeline in the analysis of data from 18 publicly available transcriptomic data
studies. This identified links between genes involved in asparagine metabolism in
wheat roots under drought stress, wheat leaves under drought stress, and wheat
leaves under conditions of sulfur and nitrogen deficiency. The network represents
a powerful aid for interpreting the interactions not only between the genes in
the pathway but also among enzymes, metabolites and smaller molecules. It
provides a concise, clear understanding of the complexity of asparagine
metabolism that could aid the interpretation of data relating to wider amino acid
metabolism and other metabolic processes.
PMID- 29938112
TI - Novel application of cryobiopsy in the diagnosis of pulmonary alveolar
proteinosis.
AB - Pulmonary alveolar proteinosis (PAP) is a rare disease diagnosed pathologically
by the build up of surfactant in the alveolar spaces. Establishing a diagnosis
usually requires invasive procedures such as bronchoalveolar lavage and forceps
biopsy to obtain tissue specimens. Infrequently, surgery is required when
histopathological results from other modalities are equivocal. Cryobiopsy has
emerged as a novel technique for obtaining lung tissues in pulmonary diseases.
Recently, cryobiopsy has been used to diagnose diffuse parenchymal lung disease,
but it has rarely been used for the diagnosis of PAP. Here, we describe a 54-year
old male businessman presenting with intermittent coughing with yellowish sputum
and dyspnoea upon exertion for half a year. Tissues from forceps biopsy fail to
yield a specific diagnosis, whereas those from cryobiopsy confirm the diagnosis
of PAP. Cryobiopsy offers several diagnostic advantages compared to conventional
techniques and appears to be a potential diagnostic tool for diagnosing PAP.
PMID- 29938113
TI - The G protein-coupled estrogen receptor agonist, G-1, attenuates BK channel
activation in cerebral arterial smooth muscle cells.
AB - The G protein-coupled estrogen receptor (GPER) is a significant modulator of
arterial contractility and blood flow. The GPER-specific activator, G-1, has been
widely used to characterize GPER function in a variety of tissue types. Large
conductance, calcium (Ca2+)-activated K+ (BK) channels are sensitive to 17beta
estradiol (17beta-E2) and estrogenic compounds (e.g., tamoxifen, ICI 182 780)
that target estrogen receptors. The purpose of this study was to investigate the
effects of G-1 on BK channel activation and function in cerebral arterial
myocytes. Inside-out and perforated patch clamp were utilized to assess the
effects of G-1 (50 nmol.L-1-5 MUmol.L-1) on BK channel activation and currents in
cerebral arterial myocytes. Pressurized artery myography was used to investigate
the effects of G-1 on vasodilatory response and BK channel function of cerebral
resistance size arteries. G-1 reduced BK channel activation in cerebral arterial
myocytes through elevations in BK channel mean close times. Depressed BK channel
activation following G-1 application resulted in attenuated physiological BK
currents (transient BK currents). G-1 elicited vasodilation, but reduced BK
channel function, in pressurized, endothelium-denuded cerebral arteries. These
data suggest that G-1 directly suppresses BK channel activation and currents in
cerebral arterial myocytes, BK channels being critically important in the
regulation of myocyte membrane potential and arterial contractility. Thus, GPER
mediated vasodilation using G-1 to activate the receptor may underestimate the
physiological function and relevance of GPER in the cardiovascular system.
PMID- 29938114
TI - Synergism in aluminum and mercury neurotoxicity.
AB - Aluminum and mercury are common neurotoxic contaminants in our environment - from
the air we breathe to the water that we drink to the foods that we eat. It is
remarkable that to date neither of these two well-established environmental
neurotoxins (i.e. those having a general toxicity towards brain cells) and
genotoxins (those agents which exhibit directed toxicity toward the genetic
apparatus) have been critically studied, nor have their neurotoxicities been
evaluated in human neurobiology or in cells of the human central nervous system
(CNS). In this paper we report the effects of added aluminum [sulfate; Al2(SO4)3]
and/or mercury [sulfate; HgSO4] to human neuronal-glial (HNG) cells in primary co
culture using the evolution of the pro-inflammatory transcription factor NF-kB
(p50/p65) complex as a critical indicator for the onset of inflammatory
neurodegeneration and pathogenic inflammatory signaling. As indexed by
significant induction of the NF-kB (p50/p65) complex the results indicate: (i) a
notable increase in pro-inflammatory signaling imparted by each of these two
environmental neurotoxins toward HNG cells in the ambient 20-200 nM range; and
(ii) a significant synergism in the neurotoxicity when aluminum (sulfate) and
mercury (sulfate) were added together. This is the first report on the neurotoxic
effects of aluminum sulfate and/or mercury sulfate on the initiation of
inflammatory signaling in human brain cells in primary culture. The effects
aluminum+mercury together on other neurologically important signaling molecules
or the effects of other combinations of common environmental metallic neurotoxins
to human neurobiology currently remain not well understood but certainly warrant
additional investigation and further study in laboratory animals, in human
primary tissue cultures of CNS cells, and in other neurobiologically realistic
experimental test systems.
PMID- 29938115
TI - The anticoagulant properties of cadmium telluride quantum dots.
AB - The size-dependent optical properties of quantum dots (QDs) are frequently
exploited for use in medical imaging and labelling applications. Similarly,
presented here, they also elicit profound size-dependent anticoagulant
properties. Cadmium telluride quantum dot (QDs) (3.2 nm) were shown to have a
dramatic anticoagulant effect centred on around the intrinsic coagulation
pathway, compared to their 3.6 nm counterparts. Several clinically relevant
diagnostic tests were carried out over a concentration range of the QDs and
demonstrated that the 3.2 nm QDs elicited their response on the intrinsic pathway
as a whole, yet the activity of the individual intrinsic coagulation factors was
not affected. The mechanism appears also to be strongly influenced by the
concentration of calcium ions and not cadmium ions leached from the QDs. Static
and shear-based primary haemostasis assays were also carried out, demonstrating a
profound anticoagulant effect which was independent of platelets and
phospholipids. The data presented here suggest that the physical-chemical
properties of the QDs may have a role in the modulation of haemostasis and the
coagulation cascade, in a yet not fully understood mechanism. This study has
implications for the use of similar QDs as diagnostic or therapeutic tools in
vivo, and for the occupational health and safety of those working with such
materials.
PMID- 29938116
TI - Improved Hydrological Decision Support System for the Lower Mekong River Basin
Using Satellite-Based Earth Observations.
AB - Multiple satellite-based earth observations and traditional station data along
with the Soil & Water Assessment Tool (SWAT) hydrologic model were employed to
enhance the Lower Mekong River Basin region's hydrological decision support
system. A nearest neighbor approximation methodology was introduced to fill the
Integrated Multi-satellite Retrieval for the Global Precipitation Measurement
mission (IMERG) grid points from 2001 to 2014, together with the Tropical
Rainfall Measurement Mission (TRMM) data points for continuous precipitation
forcing for our hydrological decision support system. A software tool to access
and format satellite-based earth observation systems of precipitation and minimum
and maximum air temperatures was developed and is presented. Our results suggest
that the model-simulated streamflow utilizing TRMM and IMERG forcing data was
able to capture the variability of the observed streamflow patterns in the Lower
Mekong better than model-simulated streamflow with in-situ precipitation station
data. We also present satellite-based and in-situ precipitation adjustment maps
that can serve to correct precipitation data for the Lower Mekong region for use
in other applications. The inconsistency, scarcity, poor spatial representation,
difficult access and incompleteness of the available in-situ precipitation data
for the Mekong region make it imperative to adopt satellite-based earth
observations to pursue hydrologic modeling.
PMID- 29938117
TI - An MM and QM Study of Biomimetic Catalysis of Diels-Alder Reactions Using
Cyclodextrins.
AB - We performed a computational investigation of the mechanism by which
cyclodextrins (CDs) catalyze Diels-Alder reactions between 9-anthracenemethanol
and N-cyclohexylmaleimide. Hydrogen bonds (Hbonds) between N-cyclohexylmaleimide
and the hydroxyl groups of cyclodextrins were suggested to play an important role
in this catalytic process. However, our free energy calculations and molecular
dynamics simulations showed that these Hbonds are not stable, and quantum
mechanical calculations suggested that the reaction is not promoted by these
Hbonds. The binding of 9-anthracenemethanol and N-cyclohexylmaleimide to
cyclodextrins was the key to the catalytic process. Cyclodextrins act as a
container to hold the two reactants in the cavity, pre-organize them for the
reactions, and thus reduce the entropy penalty to the activation free energy.
Dimethyl-beta-CD was a better catalyst for this specific reaction than beta-CD
because of its stronger van der Waals interaction with the pre-organized
reactants and its better performance in reducing the activation energy. This
computational work sheds light on the mechanism of the catalytic reaction by
cyclodextrins and introduces new perspectives of supramolecular catalysis.
PMID- 29938118
TI - An Overview of Network-Based and -Free Approaches for Stochastic Simulation of
Biochemical Systems.
AB - Stochastic simulation has been widely used to model the dynamics of biochemical
reaction networks. Several algorithms have been proposed that are exact solutions
of the chemical master equation, following the work of Gillespie. These
stochastic simulation approaches can be broadly classified into two categories:
network-based and -free simulation. The network-based approach requires that the
full network of reactions be established at the start, while the network-free
approach is based on reaction rules that encode classes of reactions, and by
applying rule transformations, it generates reaction events as they are needed
without ever having to derive the entire network. In this study, we compare the
efficiency and limitations of several available implementations of these two
approaches. The results allow for an informed selection of the implementation and
methodology for specific biochemical modeling applications.
PMID- 29938120
TI - A Marketing Plan for Scientists: Building Effective Products and Connecting with
Stakeholders in Meaningful Ways.
PMID- 29938119
TI - Predicting Men's Immediate Reactions to a Simulated Date's Sexual Rejection: The
Effects of Hostile Masculinity, Impersonal Sex, and Hostile Perceptions of the
Woman.
AB - Objective: Aggression is a common response to many types of social rejection. Men
who respond aggressively to a woman's sexual rejection are likely to score high
on risk factors associated with sexual aggression and to convince themselves that
she is at fault. This study investigated how sexual dominance motivation and
casual sex attitudes interact with "in the moment" hostile perceptions of the
woman to predict the likelihood of an aggressive response. Method: Male
participants (N = 77) completed an online survey including self-report measures
of sexual dominance motivation and casual sex attitudes. In a separate session,
participants completed a laboratory study in which they interacted with a female
agent in a dating simulation, allowing them to make nonsexual choices, sexual
choices that were accepted, and sexual choices that were rejected. Immediate
responses to sexual rejection were categorized as aggressive (n = 25) or
nonaggressive (n = 52). After the simulation ended, participants answered
questions about their perceptions of the situation and the woman. Moderated
multiple logistic regression analyses were used to test the hypotheses. Results:
The hypothesized interactions were found such that men with high scores on sexual
dominance motivation and positive attitudes about casual sex had a greater
probability of responding aggressively when they formed extremely hostile
perceptions of the woman who rejected them. Conclusions: These findings provide
insight into the processes by which men respond aggressively to women's refusals,
and highlight the need for training that encourages benevolent attributions and
nonviolent strategies to deal with sexual rejection.
PMID- 29938121
TI - Iron(II)-Catalyzed Azidotrifluoromethylation of Olefins and N-Heterocycles for
Expedient Vicinal Trifluoromethyl Amine Synthesis.
AB - We report herein an iron-catalyzed azidotrifluoromethylation method for expedient
vicinal trifluoromethyl primary-amine synthesis. This method is effective for a
broad range of olefins and N-heterocycles, and it facilitates efficient synthesis
of a wide variety of vicinal trifluoromethyl primary amines, including those that
prove difficult to synthesize with existing approaches. Our preliminary
mechanistic studies revealed that the catalyst-promoted azido-group transfer
proceeds through a carbo-radical instead of a carbocation species.
Characterization of an active iron catalyst through X-ray crystallographic
studies suggests that in situ generated, structurally novel iron-azide complexes
promote the oxidant activation and selective azido-group transfer.
PMID- 29938122
TI - Chip-scale high Q-factor glassblown microspherical shells for magnetic sensing.
AB - A whispering gallery mode resonator based magnetometer using chip-scale glass
microspherical shells is described. A neodynium micro-magnet is elastically
coupled and integrated on top of the microspherical shell structure that enables
transduction of the magnetic force experienced by the magnet in external magnetic
fields into an optical resonance frequency shift. High quality factor optical
microspherical shell resonators with ultra-smooth surfaces have been successfully
fabricated and integrated with magnets to achieve Q-factors of greater than 1.1 *
107 and have shown a resonance shift of 1.43 GHz/mT (or 4.0 pm/mT) at 760 nm
wavelength. The main mode of action is mechanical deformation of the microbubble
with a minor contribution from the photoelastic effect. An experimental limit of
detection of 60 nT Hz-1/2 at 100 Hz is demonstrated. A theoretical
thermorefractive limited detection limit of 52 pT Hz-1/2 at 100 Hz is calculated
from the experimentally derived sensitivity. The paper describes the mode of
action, sensitivity and limit of detection is evaluated for the chip-scale
whispering gallery mode magnetometer.
PMID- 29938123
TI - Discovery of a stem-like multipotent cell fate.
AB - Adipose derived stem cells (ASCs) can be obtained from lipoaspirates and induced
in vitro to differentiate into bone, cartilage, and fat. Using this powerful
model system we show that after in vitro adipose differentiation a population of
cells retain stem-like qualities including multipotency. They are lipid (-),
retain the ability to propagate, express two known stem cell markers, and
maintain the capacity for trilineage differentiation into chondrocytes,
adipocytes, and osteoblasts. However, these cells are not traditional stem cells
because gene expression analysis showed an overall expression profile similar to
that of adipocytes. In addition to broadening our understanding of cellular
multipotency, our work may be particularly relevant to obesity-associated
metabolic disorders. The adipose expandability hypothesis proposes that inability
to differentiate new adipocytes is a primary cause of metabolic syndrome in
obesity, including diabetes and cardiovascular disease. Here we have defined a
differentiation-resistant stem-like multipotent cell population that may be
involved in regulation of adipose expandability in vivo and may therefore play
key roles in the comorbidities of obesity.
PMID- 29938124
TI - Comparing stemness gene expression between stem cell subpopulations from
peripheral blood and adipose tissue.
AB - Cell therapy presents a promising alternative for the treatment of degenerative
diseases. The main sources of adult stem cells are bone marrow, adipose tissue
and peripheral blood. Within those tissues, there are cell subpopulations that
share pluripotential characteristics. Nevertheless, there is insufficient data to
determine which of these stem cell subtypes would have a better possibility to
differentiate to a specific tissue. The objective of this research was to analyze
and compare the stemness genes expression from peripheral blood and adipose
tissue of plastic adherent cells, and those immune-selected by the CD133+ and
CD271+ membrane markers. On all cell subpopulation groups, self-renew capacity,
the membranes markers CD73, CD90 and CD105, as well as the stemness genes NANOG,
OCT4, SOX2, REX1, NOTCH1 and, NESTIN expression were analyzed. Results showed
that all samples presented the minimal criteria to define them as human stem
cells. All cell subpopulation were capable of self-renewal. Nevertheless, the
subpopulation cell types showed differences on the time needed to reach
confluence. The slowest doubling times were for those cells bearing the CD133
marker from both sources. Surface markers determined by flow cytometry were
positive for CD73, CD90 and, CD105, and negative for CD45. The stemness gene
expression was positive in all subpopulation. However, there were significant
differences in the amount and pattern of expression among them. Those differences
could be advantageous in finding the best option for their application on cell
therapy. Cells with high expression of OCT4 gene could be a better opportunity
for neuron differentiation like CD133+ blood cells. On the other hand, lowest
expression of NOTCH1 on CD271+ cells from the same source could be a better
possibility for myoblast differentiation. The observed differences could be used
as an advantage to find which cell type and from the different source; this
represents the best option for its application on cell therapy. Experiments
focused on the best response to specific differentiation, are conducted in order
to confirm those possibilities.
PMID- 29938125
TI - Analysis of the regulation pathways via microarray and miRNA studies: human
embryonic stem cells to treat diabetes mellitus type-II.
AB - Diabetes mellitus occurs either due to an autoimmune destruction of beta cells
(Type 1) or resistance to insulin effects (Type 2). Diverse conventional
medications are used for treatment of diabetes, which is associated with long
term complications such as kidney failure, blindness, and stroke. We recently
showed the potential of human embryonic stem cells (hESCs) in 95 patients with
type 2 diabetes. In the present study, we use the microarray and miRNA studies to
prove why hESCs are effective in diabetes. Three samples of hESCs were cultured
and microarray technology was used for the analysis of diabetic pathways. The
gene targets for miRNA were analyzed using gene ontology (GO) and DAVID database.
Genes involved in the diabetic pathways were classified in accordance with GO
analysis. Pathways for these genes were determined using Reactome and Panther
databases. The up and down-regulation of all the genes involved were confirmed
with the significant p-values. Pathways for insulin secretion, binding and its
positive regulation were up-regulated while the pathways for negative regulation
of insulin were significantly down-regulated. hESCs cultured at our facility have
the capability to regenerate the pancreatic beta cells after transplantation; as
the insulin secretion pathways were significantly up-regulated.
PMID- 29938126
TI - Differential Effect of LPS on Glucose, Lactate and Inflammatory Markers in the
Lungs of Normal and Diabetic Mice.
AB - Elevation of blood glucose results in increased glucose in the fluid that lines
the surface of the airways and this is associated with an increased
susceptibility to infection with respiratory pathogens. Infection induces an
inflammatory response in the lung, but how this is altered by hyperglycemia and
how this affects glucose, lactate and cytokine concentrations in the airway
surface liquid is not understood. We used Wild Type (WT) and glucokinase
heterozygote (GK+/-) mice to investigate the effect of hyperglycemia, with and
without LPS-induced inflammatory responses, on airway glucose, lactate,
inflammatory cells and cytokines measured in Bronchoalveolar Lavage Fluid (BALF).
We found that glucose and lactate concentrations in BALF were elevated in GK+/-
compared to WT mice and that there was a direct correlation between blood glucose
and BALF glucose concentrations. LPS challenge increased BALF inflammatory cell
numbers and this correlated with decreased glucose and increased lactate
concentrations although the effect was less in GK+/- compared to WT mice. All
cytokines measured (except IL-2) increased in BALF with LPS challenge. However,
concentrations of TNFalpha, INFgamma, IL-1beta and IL-2 were less in GK+/-
compared to WT mice. This study shows that the normal glucose/lactate environment
of the airway surface liquid is altered by hyperglycemia and the inflammatory
response. These data indicate that inflammatory cells utilize BALF glucose and
that production of lactate and cytokines is compromised in hyperglycemic GK+/-
mice.
PMID- 29938127
TI - Using a participatory approach to develop and implement the UK ME/CFS Biobank.
PMID- 29938128
TI - Intrauterine Inflammation, Epigenetics, and Microbiome Influences on Preterm
Infant Health.
AB - Purpose of Review: Significant research reveals that the microbiome modulates
perinatal and postnatal health. This review aims to examine mechanisms by which
intrauterine infection, the epigenome, and microbiome specifically influence
preterm infant health outcomes. Recent Findings: Intrauterine infection is a
primary cause of preterm birth and can cause alterations in gene expression and
epigenetic programming as well as postnatal inflammatory responses in the
offspring. Insights from our own studies demonstrate epigenetic modifications of
TLRs associated with exposure to intrauterine inflammation, as well as a cross
talk between host epigenome and microbiome. Lastly, the gut microbiome modulates
maturation of inflammatory pathways, which influences the development of preterm
infants. Summary: We present a unifying theme that preterm infant outcomes are
associated with modulation of host immune and inflammatory responses, which are
influenced by acute intrauterine infection, epigenetic, and microbiome factors.
PMID- 29938129
TI - Mechanisms of Pathology-Induced Neural Stem Cell Plasticity and Neural
Regeneration in Adult Zebrafish Brain.
AB - Purpose of the Review: The purpose of this study is to review the current
knowledge on the damage-induced molecular programs that underlie the regenerative
ability in zebrafish brain. Recent Findings: Neural stem cells are the reservoir
for new neurons during development and regeneration of the vertebrate brains.
Pathological conditions such as neurodegenerative diseases hamper neural stem
cell plasticity and neurogenic outcome in humans, whereas adult zebrafish brain
can enhance proliferation and neurogenic capacity of its neural stem cells
despite the incipient pathology. Evidence suggests that zebrafish uses damage
induced molecular programs to enable neural stem cells to efficiently initiate
regeneration. Since this aptitude may be harnessed for regenerative therapies in
human brain, understanding the molecular programs regulating neural stem cell
proliferation and quiescence in zebrafish is of utmost importance for clinical
efforts. Summary: Specific molecular programs that are different than those in
the homeostatic conditions regulate adult zebrafish neural stem cell plasticity
and the regenerative capacity after injury and neurodegeneration. These programs
can serve as candidates for stem cell-based regenerative therapies in humans.
PMID- 29938130
TI - Characterization of the ATPase FlaI of the motor complex of the Pyrococcus
furiosus archaellum and its interactions between the ATP-binding protein FlaH.
AB - The archaellum, the rotating motility structure of archaea, is best studied in
the crenarchaeon Sulfolobus acidocaldarius. To better understand how assembly and
rotation of this structure is driven, two ATP-binding proteins, FlaI and FlaH of
the motor complex of the archaellum of the euryarchaeon Pyrococcus furiosus, were
overexpressed, purified and studied. Contrary to the FlaI ATPase of S.
acidocaldarius, which only forms a hexamer after binding of nucleotides, FlaI of
P. furiosus formed a hexamer in a nucleotide independent manner. In this hexamer
only 2 of the ATP binding sites were available for binding of the fluorescent ATP
analog MANT-ATP, suggesting a twofold symmetry in the hexamer. P. furiosus FlaI
showed a 250-fold higher ATPase activity than S. acidocaldarius FlaI. Interaction
studies between the isolated N- and C-terminal domains of FlaI showed
interactions between the N- and C-terminal domains and strong interactions
between the N-terminal domains not previously observed for ATPases involved in
archaellum assembly. These interactions played a role in oligomerization and
activity, suggesting a conformational state of the hexamer not observed before.
Further interaction studies show that the C-terminal domain of PfFlaI interacts
with the nucleotide binding protein FlaH. This interaction stimulates the ATPase
activity of FlaI optimally at a 1:1 stoichiometry, suggesting that hexameric
PfFlaI interacts with hexameric PfFlaH. These data help to further understand the
complex interactions that are required to energize the archaellar motor.
PMID- 29938131
TI - Ecotoxicity of disinfectant benzalkonium chloride and its mixture with
antineoplastic drug 5-fluorouracil towards alga Pseudokirchneriella subcapitata.
AB - Background: Benzalkonium chloride (BAC) is one of the most common ingredients of
the disinfectants. It is commonly detected in surface and wastewaters where it
can interact with the residues of pharmaceuticals that are also common wastewater
pollutants. Among the latter, the residues of antineoplastic drugs are of
particular concern as recent studies showed that they can induce adverse effect
in aquatic organisms at environmentally relevant concentrations. Methods:
Ecotoxicity of BAC as an individual compound and in a binary mixture with an
antineoplastic drug 5-fluorouracil (5-FU) was determined towards alga
Pseudokirchneriella subcapitata, a representative of primary producers. The
toxicity of the BAC+5-FU binary mixture was predicted by the two basic models:
concentration addition (CA) and independent action (IA), and compared to the
experimentally determined toxicity. Additionally combination index (CI) was
calculated to determine the type of interaction. Results: After 72 h exposure to
BAC a concentration dependent growth inhibition of P. subcapitata was observed
with an EC50 0.255 mg/L. Comparing the predicted no effect concentration to the
measured concentrations in the surface waters indicate that BAC at current
applications and occurrence in aquatic environment may affect algal populations.
The measured toxicity of the mixture was higher from the predicted and calculated
CI confirmed synergistic effect on the inhibition of algal growth, at least at
EC50 concentration. The observed synergism may have impact on the overall
toxicity of wastewaters, whereas it is less likely for general environments
because the concentrations of 5-FU are several orders of magnitude lower from its
predicted no effect concentration. Discussion: These results indicate that
combined effects of mixtures of disinfectants and antineoplastic drugs should be
considered in particular when dealing with environmental risk assessment as well
as the management of municipal and hospital wastewaters.
PMID- 29938132
TI - Is perfectionism associated with academic burnout through repetitive negative
thinking?
AB - Academic burnout is prevalent among university students, although understanding
of what predicts burnout is limited. This study aimed to test the direct and
indirect relationship between two dimensions of perfectionism (Perfectionistic
Concerns and Perfectionistic Strivings) and the three elements of Academic
Burnout (Exhaustion, Inadequacy, and Cynicism) through Repetitive Negative
Thinking. In a cross-sectional survey, undergraduate students (n = 126, Mage =
23.64, 79% female) completed well-validated measures of Perfectionism, Repetitive
Negative Thinking, and Academic Burnout. Perfectionistic Concerns was directly
associated with all elements of burnout, as well as indirectly associated with
Exhaustion and Cynicism via Repetitive Negative Thinking. Perfectionistic
Strivings was directly associated with less Inadequacy and Cynicism; however,
there were no indirect associations between Perfectionistic Strivings and
Academic Burnout operating through Repetitive Negative Thinking. Repetitive
Negative Thinking was also directly related to more burnout Exhaustion and
Inadequacy, but not Cynicism. It is concluded that future research should
investigate whether interventions targeting Perfectionistic Concerns and
Repetitive Negative Thinking can reduce Academic Burnout in university students.
PMID- 29938133
TI - Comparison of cryptobenthic reef fish communities among microhabitats in the Red
Sea.
AB - Knowledge of community structure within an ecosystem is essential when trying to
understand the function and importance of the system and when making related
management decisions. Within the larger ecosystem, microhabitats play an
important role by providing inhabitants with a subset of available resources. On
coral reefs, cryptobenthic fishes encompass many groups and make up an important
proportion of the biodiversity. However, these fishes are relatively small,
exhibit extreme visual or behavioral camouflage, and, therefore, are often
overlooked. We examined the differences in fish community structure between three
common reef microhabitats (live hard coral, dead coral rubble, and sand) using
ichthyocide stations in the central Red Sea. Using a combination of morphological
and genetic (cytochrome oxidase I (COI) barcoding) techniques, we identified 326
individuals representing 73 species spread across 17 families, from fifteen 1 m2
quadrats. Fish assemblages in the three microhabitats were significantly
different from each other. Rubble microhabitats yielded the highest levels of
fish abundance, richness, and diversity, followed by hard coral, and then sand.
The results show that benthic composition, even at a small scale, influences
cryptobenthic communities. This study also provides new COI sequence data to
public databases, in order to further the research of cryptobenthic fishes in the
Red Sea region.
PMID- 29938134
TI - Availability of Nanopore sequences in the genome taxonomy for Vibrionaceae
systematics: Rumoiensis clade species as a test case.
AB - Whole genome sequence comparisons have become essential for establishing a robust
scheme in bacterial taxonomy. To generalize this genome-based taxonomy, fast,
reliable, and cost-effective genome sequencing methodologies are required.
MinION, the palm-sized sequencer from Oxford Nanopore Technologies, enables rapid
sequencing of bacterial genomes using minimal laboratory resources. Here we
tested the ability of Nanopore sequences for the genome-based taxonomy of
Vibrionaceae and compared Nanopore-only assemblies to complete genomes of five
Rumoiensis clade species: Vibrio aphrogenes, V. algivorus, V. casei, V.
litoralis, and V. rumoiensis. Comparison of overall genome relatedness indices
(OGRI) and multilocus sequence analysis (MLSA) based on Nanopore-only assembly
and Illumina or hybrid assemblies revealed that errors in Nanopore-only assembly
do not influence average nucleotide identity (ANI), in silico DNA-DNA
hybridization (DDH), G+C content, or MLSA tree topology in Vibrionaceae. Our
results show that the genome sequences from Nanopore-based approach can be used
for rapid species identification based on the OGRI and MLSA.
PMID- 29938135
TI - Unusually low genetic divergence at COI barcode locus between two species of
intertidal Thalassaphorura (Collembola: Onychiuridae).
AB - Species classification is challenging when taxa display limited morphological
differences. In this paper, we combined morphology and DNA barcode data to
investigate the complicated taxonomy of two Onychiurid Collembolan species.
Thalassaphorura thalassophila and Thalassaphorura debilis are among the most
common arthropod species in intertidal ecosystems and are often considered to be
synonymous. Based on morphological and barcode analyses of fresh material
collected in their type localities, we redescribed and compared the two species.
However, their morphological distinctiveness was supported by a molecular
divergence much smaller than previously reported at the interspecific level among
Collembola. This divergence was even smaller than inter-population divergences
recognized in the related edaphic species T. zschokkei, as well as those known
between MOTUs within many Collembolan species. Our results may indicate a link
between low genetic interspecific divergence and intertidal habitat, as the only
biological peculiarity of the two species of interest compared to other
Collembolan species analyzed to date is their strict intertidal life.
PMID- 29938136
TI - Safe exposure distances for transcranial magnetic stimulation based on computer
simulations.
AB - The results of a computer simulation examining the compliance of a given
transcranial magnetic stimulation device to the 2010 International Commission on
Non-Ionizing Radiation Protection (ICNIRP) guidelines are presented. The
objective was to update the safe distance estimates with the most current safety
guidelines, as well as comparing these to values reported in previous
publications. The 3D data generated was compared against results available in the
literature, regarding the MCB-70 coil by Medtronic. Regarding occupational
exposure, safe distances of 1.46 m and 0.96 m are derived from the simulation
according to the 2003 and 2010 ICNIRP guidelines, respectively. These values are
then compared to safe distances previously reported in other studies.
PMID- 29938137
TI - Individual-based simulation of the spatial and temporal dynamics of
macroinvertebrate functional groups provides insights into benthic community
assembly mechanisms.
AB - The complexity and scales of the processes that shape communities of marine
benthic macroinvertebrates has limited our understanding of their assembly
mechanisms and the potential to make projections of their spatial and temporal
dynamics. Individual-based models can shed light on community assembly
mechanisms, by allowing observed spatiotemporal patterns to emerge from first
principles about the modeled organisms. Previous work in the Rance estuary
(Brittany, France) revealed the principal functional components of its benthic
macroinvertebrate communities and derived a set of functional relationships
between them. These elements were combined here for the development of a dynamic
and spatially explicit model that operates at two spatial scales. At the fine
scale, modeling each individual's life cycle allowed the representation of
recruitment, inter- and intra-group competition, biogenic habitat modification
and predation mortality. Larval dispersal and environmental filtering due to the
tidal characteristics of the Rance estuary were represented at the coarse scale.
The two scales were dynamically linked and the model was parameterized on the
basis of theoretical expectations and expert knowledge. The model was able to
reproduce some patterns of alpha- and beta-diversity that were observed in the
Rance estuary in 1995. Model analysis demonstrated the role of local and regional
processes, particularly early post-settlement mortality and spatially restricted
dispersal, in shaping marine benthos. It also indicated biogenic habitat
modification as a promising area for future research. The combination of this
mechanism with different substrate types, along with the representation of
physical disturbances and more trophic categories, could increase the model's
realism. The precise parameterization and validation of the model is expected to
extend its scope from the exploration of community assembly mechanisms to the
formulation of predictions about the responses of community structure and
functioning to environmental change.
PMID- 29938138
TI - Intein-mediated backbone cyclization of entolimod confers enhanced
radioprotective activity in mouse models.
AB - Background: Entolimod is a Salmonella enterica flagellin derivate. Previous work
has demonstrated that entolimod effectively protects mice and non-human primates
from ionizing radiation. However, it caused a "flu-like" syndrome after
radioprotective and anticancer clinical application, indicating some type of
immunogenicity and toxicity. Cyclization is commonly used to improve the in vivo
stability and activity of peptides and proteins. Methods: We designed and
constructed cyclic entolimod using split Nostoc punctiforme DnaE intein with
almost 100% cyclization efficiency. We adopted different strategies to purify the
linear and circular entolimod due to their different topologies. Both of linear
and circular entolimod were first purified by Ni-chelating affinity
chromatography, and then the linear and circular entolimod were purified by size
exclusion and ion-exchange chromatography, respectively. Results: The circular
entolimod showed significantly increased both the in vitro NF-kappaB signaling
and in vivo radioprotective activity in mice. Conclusion: Our data indicates that
circular entolimod might be a good candidate for further clinical investigation.
PMID- 29938139
TI - Comparative demography of commercially-harvested snappers and an emperor from
American Samoa.
AB - The age-based life history of two commercially-important species of snapper
(Lutjanidae) and one emperor (Lethrinidae) were characterized from the nearshore
fishery of Tutuila, American Samoa. Examination of sagittal otoliths across
multiple months and years confirmed the annual deposition of increments and
highlighted marked variation in life-history patterns among the three meso
predator species. The humpback red snapper Lutjanus gibbus is a medium-bodied
gonochoristic species which exhibits striking sexual dimorphism in length-at-age
and consequent growth trajectories and has a life span estimated to be at least
27 years. The yellow-lined snapper Lutjanus rufolineatus is a small-bodied
gonochore with weak sexual dimorphism, early maturation, and a short life span of
at least 12 years. The yellow-lip emperor Lethrinus xanthochilus is a large
bodied species with a moderate life span (estimated to be at least 19 years in
this study), rapid initial growth, and a more complex sexual ontogeny likely
involving pre- or post-maturational sex change, although this remains unresolved
at present. Ratios of natural to fishing mortality indicate a low level of
prevailing exploitation for all three species, which is supported by low
proportions of immature female length classes captured by the fishery. However,
considerable demographic variability among the three species highlights the value
of detailed age-based information as a necessary component for informing
monitoring efforts and future management decisions.
PMID- 29938141
TI - A Case of Pancreatic Pseudocyst Complicated by Pseudoaneurysm.
AB - Pancreatic pseudocyst is a complication that can arise in both acute and chronic
pancreatitis. Overtime, this encapsulated enzyme-rich fluid collection may erode
into surrounding vasculature and result in the formation of a pseudoaneurysm.
Pseudoaneurysms can rupture into the gastrointestinal tract and present as upper,
lower, and biliary bleeding. Evaluation of pancreatic pseudocysts involves
computed tomography imaging or magnetic resonance imaging for both identification
and monitoring. Esophagogastroduodenoscopy (EGD) and endoscopic ultrasound (EUS)
can be done to further visualize the lesion. In the presence of gastrointestinal
bleed, management involves the combination of interventional radiology and
surgery.
PMID- 29938140
TI - Transcriptomic evidence for involvement of reactive oxygen species in Rhizoctonia
solani AG1 IA sclerotia maturation.
AB - Rhizoctonia solani AG1 IA is a soil-borne fungal phytopathogen that can
significantly harm crops resulting in economic loss. This species overwinters in
grass roots and diseased plants, and produces sclerotia that infect future crops.
R. solani AG1 IA does not produce spores; therefore, understanding the molecular
mechanism of sclerotia formation is important for crop disease control. To
identify the genes involved in this process for the development of disease
control targets, the transcriptomes of this species were determined at three
important developmental stages (mycelium, sclerotial initiation, and sclerotial
maturation) using an RNA-sequencing approach. A total of 5,016, 6,433, and 5,004
differentially expressed genes (DEGs) were identified in the sclerotial
initiation vs. mycelial, sclerotial maturation vs. mycelial, and sclerotial
maturation vs. sclerotial initiation stages, respectively. Moreover, gene
ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses showed
that these DEGs were enriched in diverse categories, including oxidoreductase
activity, carbohydrate metabolic process, and oxidation-reduction processes. A
total of 12 DEGs were further verified using reverse transcription quantitative
PCR. Among the genes examined, NADPH oxidase 1 (NOX1) and superoxide dismutase
(SOD) were highly induced in the stages of sclerotial initiation and maturation.
In addition, the highest reactive oxygen species (ROS) production levels were
detected during sclerotial initiation, and enzyme activities of NOX1, SOD, and
catalase (CAT) matched with the gene expression profiles. To further evaluate the
role of ROS in sclerotial formation, R. solani AG1 IA was treated with the CAT
inhibitor aminotriazole and H2O2, resulting in the early differentiation of
sclerotia. Taken together, this study provides useful information toward
understanding the molecular basis of R. solani AG1 IA sclerotial formation and
maturation, and identified the important role of ROS in these processes.
PMID- 29938142
TI - Soil Carbon Dynamics in Soybean Cropland and Forests in Mato Grosso, Brazil.
AB - Climate and land use models predict that tropical deforestation and conversion to
cropland will produce a large flux of soil carbon (C) to the atmosphere from
accelerated decomposition of soil organic matter (SOM). However, the C flux from
the deep tropical soils on which most intensive crop agriculture is now expanding
remains poorly constrained. To quantify the effect of intensive agriculture on
tropical soil C, we compared C stocks, radiocarbon, and stable C isotopes to 2 m
depth from forests and soybean cropland created from former pasture in Mato
Grosso, Brazil. We hypothesized that soil disturbance, higher soil temperatures
(+2 degrees C), and lower OM inputs from soybeans would increase soil C turnover
and deplete C stocks relative to nearby forest soils. However, we found reduced C
concentrations and stocks only in surface soils (0-10 cm) of soybean cropland
compared with forests, and these differences could be explained by soil mixing
during plowing. The amount and Delta14C of respired CO2 to 50 cm depth were
significantly lower from soybean soils, yet CO2 production at 2 m deep was low in
both forest and soybean soils. Mean surface soil delta13C decreased by 0.50/00
between 2009 and 2013 in soybean cropland, suggesting low OM inputs from
soybeans. Together these findings suggest the following: (1) soil C is relatively
resistant to changes in land use and (2) conversion to cropland caused a small,
measurable reduction in the fast-cycling C pool through reduced OM inputs,
mobilization of older C from soil mixing, and/or destabilization of SOM in
surface soils.
PMID- 29938143
TI - Soil Moisture-Temperature Coupling in a Set of Land Surface Models.
AB - The land surface controls the partitioning of water and energy fluxes and
therefore plays a crucial role in the climate system. The coupling between soil
moisture and air temperature, in particular, has been shown to affect the
severity and occurrence of temperature extremes and heat waves. Here we study
soil moisture-temperature coupling in five land surface models, focusing on the
terrestrial segment of the coupling in the warm season. All models are run off
line over a common period with identical atmospheric forcing data, in order to
allow differences in the results to be attributed to the models' partitioning of
energy and water fluxes. Coupling is calculated according to two semiempirical
metrics, and results are compared to observational flux tower data. Results show
that the locations of the global hot spots of soil moisture-temperature coupling
are similar across all models and for both metrics. In agreement with previous
studies, these areas are located in transitional climate regimes. The magnitude
and local patterns of model coupling, however, can vary considerably. Model
coupling fields are compared to tower data, bearing in mind the limitations in
the geographical distribution of flux towers and the differences in
representative area of models and in situ data. Nevertheless, model coupling
correlates in space with the tower-based results (r = 0.5-0.7), with the
multimodel mean performing similarly to the best-performing model. Intermodel
differences are also found in the evaporative fractions and may relate to errors
in model parameterizations and ancillary data of soil and vegetation
characteristics.
PMID- 29938144
TI - LOFAR Lightning Imaging: Mapping Lightning With Nanosecond Precision.
AB - Lightning mapping technology has proven instrumental in understanding lightning.
In this work we present a pipeline that can use lightning observed by the LOw
Frequency ARray (LOFAR) radio telescope to construct a 3-D map of the flash. We
show that LOFAR has unparalleled precision, on the order of meters, even for
lightning flashes that are over 20 km outside the area enclosed by LOFAR antennas
(~3,200 km2), and can potentially locate over 10,000 sources per lightning flash.
We also show that LOFAR is the first lightning mapping system that is sensitive
to the spatial structure of the electrical current during individual lightning
leader steps.
PMID- 29938145
TI - Drought Persistence Errors in Global Climate Models.
AB - The persistence of drought events largely determines the severity of
socioeconomic and ecological impacts, but the capability of current global
climate models (GCMs) to simulate such events is subject to large uncertainties.
In this study, the representation of drought persistence in GCMs is assessed by
comparing state-of-the-art GCM model simulations to observation-based data sets.
For doing so, we consider dry-to-dry transition probabilities at monthly and
annual scales as estimates for drought persistence, where a dry status is defined
as negative precipitation anomaly. Though there is a substantial spread in the
drought persistence bias, most of the simulations show systematic underestimation
of drought persistence at global scale. Subsequently, we analyzed to which degree
(i) inaccurate observations, (ii) differences among models, (iii) internal
climate variability, and (iv) uncertainty of the employed statistical methods
contribute to the spread in drought persistence errors using an analysis of
variance approach. The results show that at monthly scale, model uncertainty and
observational uncertainty dominate, while the contribution from internal
variability is small in most cases. At annual scale, the spread of the drought
persistence error is dominated by the statistical estimation error of drought
persistence, indicating that the partitioning of the error is impaired by the
limited number of considered time steps. These findings reveal systematic errors
in the representation of drought persistence in current GCMs and suggest
directions for further model improvement.
PMID- 29938146
TI - An Uncertainty Data Set for Passive Microwave Satellite Observations of Warm
Cloud Liquid Water Path.
AB - The first extended comprehensive data set of the retrieval uncertainties in
passive microwave observations of cloud liquid water path (CLWP) for warm oceanic
clouds has been created for practical use in climate applications. Four major
sources of systematic errors were considered over the 9-year record of the
Advanced Microwave Scanning Radiometer-EOS (AMSR-E): clear-sky bias, cloud-rain
partition (CRP) bias, cloud-fraction-dependent bias, and cloud temperature bias.
Errors were estimated using a unique merged AMSR-E/Moderate resolution Imaging
Spectroradiometer Level 2 data set as well as observations from the Cloud-Aerosol
Lidar with Orthogonal Polarization and the CloudSat Cloud Profiling Radar. To
quantify the CRP bias more accurately, a new parameterization was developed to
improve the inference of CLWP in warm rain. The cloud-fraction-dependent bias was
found to be a combination of the CRP bias, an in-cloud bias, and an adjacent
precipitation bias. Globally, the mean net bias was 0.012 kg/m2, dominated by the
CRP and in-cloud biases, but with considerable regional and seasonal variation.
Good qualitative agreement between a bias-corrected AMSR-E CLWP climatology and
ship observations in the Northeast Pacific suggests that the bias estimates are
reasonable. However, a possible underestimation of the net bias in certain
conditions may be due in part to the crude method used in classifying
precipitation, underscoring the need for an independent method of detecting rain
in warm clouds. This study demonstrates the importance of combining visible
infrared imager data and passive microwave CLWP observations for estimating
uncertainties and improving the accuracy of these observations.
PMID- 29938147
TI - Is Black Carbon an Unimportant Ice-Nucleating Particle in Mixed-Phase Clouds?
AB - It has been hypothesized that black carbon (BC) influences mixed-phase clouds by
acting as an ice-nucleating particle (INP). However, the literature data for ice
nucleation by BC immersed in supercooled water are extremely varied, with some
studies reporting that BC is very effective at nucleating ice, whereas others
report no ice-nucleating ability. Here we present new experimental results for
immersion mode ice nucleation by BC from two contrasting fuels (n-decane and
eugenol). We observe no significant heterogeneous nucleation by either sample.
Using a global aerosol model, we quantify the maximum relative importance of BC
for ice nucleation when compared with K-feldspar and marine organic aerosol
acting as INP. Based on the upper limit from our laboratory data, we show that BC
contributes at least several orders of magnitude less INP than feldspar and
marine organic aerosol. Representations of its atmospheric ice-nucleating ability
based on older laboratory data produce unrealistic results when compared against
ambient observations of INP. Since BC is a complex material, it cannot be
unambiguously ruled out as an important INP species in all locations at all
times. Therefore, we use our model to estimate a range of values for the density
of active sites that BC particles must have to be relevant for ice nucleation in
the atmosphere. The estimated values will guide future work on BC, defining the
required sensitivity of future experimental studies.
PMID- 29938148
TI - Mineralogical Diversity and Geology of Humboldt Crater Derived Using Moon
Mineralogy Mapper Data.
AB - Moon Mineralogy Mapper (M3) spectroscopic data and high-resolution imagery data
sets were used to study the mineralogy and geology of the 207 km diameter
Humboldt crater. Analyses of M3 data, using a custom-made method for M3 spectra
continuum removal and spectral parameters calculation, reveal multiple pure
crystalline plagioclase detections within the Humboldt crater central peak
complex, hinting at its crustal origin. However, olivine, spinel, and glass are
observed in the crater walls and rims, suggesting these minerals derive from
shallower levels than the plagioclase of the central peak complex. High-calcium
pyroxenes are detected in association with volcanic deposits emplaced on the
crater's floor. Geologic mapping was performed, and the age of Humboldt crater's
units was estimated from crater counts. Results suggest that volcanic activity
within this floor-fractured crater spanned over a billion years. The felsic
mineralogy of the central peak complex region, which presumably excavated deeper
material, and the shallow mafic minerals (olivine and spinel) detected in
Humboldt crater walls and rim are not in accordance with the general view of the
structure of the lunar crust. Our observations can be explained by the presence
of a mafic pluton emplaced in the anorthositic crust prior to the Humboldt
forming impact event. Alternatively, the excavation of Australe basin ejecta
could explain the observed mineralogical detections. This highlights the
importance of detailed combined mineralogical and geological remote sensing
studies to assess the heterogeneity of the lunar crust.
PMID- 29938149
TI - The Effect of Alongcoast Advection on Pacific Northwest Shelf and Slope Water
Properties in Relation to Upwelling Variability.
AB - The Northern California Current System experiences highly variable seasonal
upwelling in addition to larger basin-scale variability, both of which can
significantly affect its water chemistry. Salinity and temperature fields from a
7 year ROMS hindcast model of this region (43 degrees N-50 degrees N), along with
extensive particle tracking, were used to study interannual variability in water
properties over both the upper slope and the midshelf bottom. Variation in slope
water properties was an order of magnitude smaller than on the shelf.
Furthermore, the primary relationship between temperature and salinity anomalies
in midshelf bottom water consisted of variation in density (cold/salty versus
warm/fresh), nearly orthogonal to the anomalies along density levels (cold/fresh
versus warm/salty) observed on the upper slope. These midshelf anomalies were
well-explained (R2 = 0.6) by the combination of interannual variability in local
and remote alongshore wind stress, and depth of the California Undercurrent (CUC)
core. Lagrangian analysis of upper slope and midshelf bottom water shows that
both are affected simultaneously by large-scale alongcoast advection of water
through the northern and southern boundaries. The amplitude of anomalies in
bottom oxygen and dissolved inorganic carbon (DIC) on the shelf associated with
upwelling variability are larger than those associated with typical variation in
alongcoast advection, and are comparable to observed anomalies in this region.
However, a large northern intrusion event in 2004 illustrates that particular,
large-scale alongcoast advection anomalies can be just as effective as upwelling
variability in changing shelf water properties on the interannual scale.
PMID- 29938150
TI - Land Ice Freshwater Budget of the Arctic and North Atlantic Oceans: 1. Data,
Methods, and Results.
AB - The freshwater budget of the Arctic and sub-polar North Atlantic Oceans has been
changing due, primarily, to increased river runoff, declining sea ice and
enhanced melting of Arctic land ice. Since the mid-1990s this latter component
has experienced a pronounced increase. We use a combination of satellite
observations of glacier flow speed and regional climate modeling to reconstruct
the land ice freshwater flux from the Greenland ice sheet and Arctic glaciers and
ice caps for the period 1958-2016. The cumulative freshwater flux anomaly
exceeded 6,300 +/- 316 km3 by 2016. This is roughly twice the estimate of a
previous analysis that did not include glaciers and ice caps outside of Greenland
and which extended only to 2010. From 2010 onward, the total freshwater flux is
about 1,300 km3/yr, equivalent to 0.04 Sv, which is roughly 40% of the estimated
total runoff to the Arctic for the same time period. Not all of this flux will
reach areas of deep convection or Arctic and Sub-Arctic seas. We note, however,
that the largest freshwater flux anomalies, grouped by ocean basin, are located
in Baffin Bay and Davis Strait. The land ice freshwater flux displays a strong
seasonal cycle with summer time values typically around five times larger than
the annual mean. This will be important for understanding the impact of these
fluxes on fjord circulation, stratification, and the biogeochemistry of, and
nutrient delivery to, coastal waters.
PMID- 29938151
TI - The Role of Oceanic Transform Faults in Seafloor Spreading: A Global Perspective
From Seismic Anisotropy.
AB - Mantle anisotropy beneath mid-ocean ridges and oceanic transforms is key to our
understanding of seafloor spreading and underlying dynamics of divergent plate
boundaries. Observations are sparse, however, given the remoteness of the oceans
and the difficulties of seismic instrumentation. To overcome this, we utilize the
global distribution of seismicity along transform faults to measure shear wave
splitting of over 550 direct S phases recorded at 56 carefully selected seismic
stations worldwide. Applying this source-side splitting technique allows for
characterization of the upper mantle seismic anisotropy, and therefore the
pattern of mantle flow, directly beneath seismically active transform faults. The
majority of the results (60%) return nulls (no splitting), while the non-null
measurements display clear azimuthal dependency. This is best simply explained by
anisotropy with a near vertical symmetry axis, consistent with mantle upwelling
beneath oceanic transforms as suggested by numerical models. It appears therefore
that the long-term stability of seafloor spreading may be associated with
widespread mantle upwelling beneath the transforms creating warm and weak faults
that localize strain to the plate boundary.
PMID- 29938152
TI - Global Ionospheric and Thermospheric Effects of the June 2015 Geomagnetic
Disturbances: Multi-Instrumental Observations and Modeling.
AB - By using data from multiple instruments, we investigate ionospheric/thermospheric
behavior during the period from 21 to 23 June 2015, when three interplanetary
shocks (IS) of different intensities arrived at Earth. The first IS was
registered at 16:45 UT on 21 June and caused ~50 nT increase in the SYM-H index.
The second IS arrived at 5:45 UT on 22 June and induced an enhancement of the
auroral/substorm activity that led to rapid increase of thermospheric neutral
mass density and ionospheric vertical total electron content at high latitudes.
Several hours later, topside electron content and electron density increased at
low latitudes on the nightside. The third and much larger IS arrived at 18:30 UT
on 22 June and initiated a major geomagnetic storm that lasted for many hours.
The storm provoked significant effects in the thermosphere and ionosphere on both
dayside and nightside. In the thermosphere, the dayside neutral mass density
exceeded the quiet time levels by 300-500%, with stronger effects in the summer
hemisphere. In the ionosphere, both positive and negative storm effects were
observed on both dayside and nightside. We compared the ionospheric observations
with simulations by the coupled Sami3 is Also a Model of the Ionosphere/Rice
Convection Model (SAMI3/RCM) model. We find rather good agreement between the
data and the model for the first phase of the storm, when the prompt penetration
electric field (PPEF) was the principal driver. At the end of the storm main
phase, when the ionospheric effects were, most likely, driven by a combination of
PPEF and thermospheric winds, the modeling results agree less with the
observations.
PMID- 29938153
TI - Wave Phenomena and Beam-Plasma Interactions at the Magnetopause Reconnection
Region.
AB - This paper reports on Magnetospheric Multiscale observations of whistler mode
chorus and higher-frequency electrostatic waves near and within a reconnection
diffusion region on 23 November 2016. The diffusion region is bounded by crescent
shaped electron distributions and associated dissipation just upstream of the X
line and by magnetic field-aligned currents and electric fields leading to
dissipation near the electron stagnation point. Measurements were made southward
of the X-line as determined by southward directed ion and electron jets. We show
that electrostatic wave generation is due to magnetosheath electron beams formed
by the electron jets as they interact with a cold background plasma and more
energetic population of magnetospheric electrons. On the magnetosphere side of
the X-line the electron beams are accompanied by a strong perpendicular electron
temperature anisotropy, which is shown to be the source of an observed rising
tone whistler mode chorus event. We show that the apex of the chorus event and
the onset of electrostatic waves coincide with the opening of magnetic field
lines at the electron stagnation point.
PMID- 29938155
TI - Study of the Equatorial and Low-Latitude Electrodynamic and Ionospheric
Disturbances During the 22-23 June 2015 Geomagnetic Storm Using Ground-Based and
Spaceborne Techniques.
AB - We use a set of ground-based instruments (Global Positioning System receivers,
ionosondes, magnetometers) along with data of multiple satellite missions (Swarm,
C/NOFS, DMSP, GUVI) to analyze the equatorial and low-latitude electrodynamic and
ionospheric disturbances caused by the geomagnetic storm of 22-23 June 2015,
which is the second largest storm in the current solar cycle. Our results show
that at the beginning of the storm, the equatorial electrojet (EEJ) and the
equatorial zonal electric fields were largely impacted by the prompt penetration
electric fields (PPEF). The PPEF were first directed eastward and caused
significant ionospheric uplift and positive ionospheric storm on the dayside, and
downward drift on the nightside. Furthermore, about 45 min after the storm
commencement, the interplanetary magnetic field (IMF) Bz component turned
northward, leading to the EEJ changing sign to westward, and to overall decrease
of the vertical total electron content (VTEC) and electron density on the
dayside. At the end of the main phase of the storm, and with the second long-term
IMF Bz southward turn, we observed several oscillations of the EEJ, which led us
to conclude that at this stage of the storm, the disturbance dynamo effect was
already in effect, competing with the PPEF and reducing it. Our analysis showed
no significant upward or downward plasma motion during this period of time;
however, the electron density and the VTEC drastically increased on the dayside
(over the Asian region). We show that this second positive storm was largely
influenced by the disturbed thermospheric conditions.
PMID- 29938154
TI - Multiscale Currents Observed by MMS in the Flow Braking Region.
AB - We present characteristics of current layers in the off-equatorial near-Earth
plasma sheet boundary observed with high time-resolution measurements from the
Magnetospheric Multiscale mission during an intense substorm associated with
multiple dipolarizations. The four Magnetospheric Multiscale spacecraft,
separated by distances of about 50 km, were located in the southern hemisphere in
the dusk portion of a substorm current wedge. They observed fast flow
disturbances (up to about 500 km/s), most intense in the dawn-dusk direction.
Field-aligned currents were observed initially within the expanding plasma sheet,
where the flow and field disturbances showed the distinct pattern expected in the
braking region of localized flows. Subsequently, intense thin field-aligned
current layers were detected at the inner boundary of equatorward moving flux
tubes together with Earthward streaming hot ions. Intense Hall current layers
were found adjacent to the field-aligned currents. In particular, we found a Hall
current structure in the vicinity of the Earthward streaming ion jet that
consisted of mixed ion components, that is, hot unmagnetized ions, cold E * B
drifting ions, and magnetized electrons. Our observations show that both the near
Earth plasma jet diversion and the thin Hall current layers formed around the
reconnection jet boundary are the sites where diversion of the perpendicular
currents take place that contribute to the observed field-aligned current pattern
as predicted by simulations of reconnection jets. Hence, multiscale structure of
flow braking is preserved in the field-aligned currents in the off-equatorial
plasma sheet and is also translated to ionosphere to become a part of the
substorm field-aligned current system.
PMID- 29938156
TI - Survey of ionospheric Pc3-5 ULF wave signatures in SuperDARN high time resolution
data.
AB - Ionospheric signatures of ultra-low frequency (ULF) wave in the Pc3-5 band (1.7
40.0 mHz) were surveyed using ~6 s resolution data from Super Dual Auroral Radar
Network (SuperDARN) radars in the northern hemisphere from 2010 to 2016.
Numerical experiments were conducted to derive wave period dependent thresholds
for automated detection of ULF waves using the Lomb-Scargle periodogram
technique. The spatial occurrence distribution, frequency characteristics,
seasonal effects, solar wind condition and geomagnetic activity level dependence
have been studied. Pc5 wave events were found to dominate at high and polar
latitudes with a most probable frequency of 2.08 +/- 0.07 mHz while Pc3-4 waves
were relatively more common at midlatitudes on the nightside with a most probable
frequency of 11.39 +/- 0.14 mHz. At high latitudes, the occurrence rate of Pc4-5
waves maximizes in the dusk sector and during winter. These events tend to occur
during low geomagnetic activity and northward interplanetary magnetic field
(IMF). For the category of radially bounded but longitudinally extended Pc4
events in the duskside ionosphere, an internal driving source is suggested. At
midlatitudes, the Pc3-4 occurrence rate maximizes premidnight and during equinox.
This tendency becomes more prominent with increasing auroral electrojet (AE)
index and during southward IMF, which suggests many of these events are Pi2 and
Pc3-4 pulsations associated with magnetotail dynamics during active geomagnetic
intervals. The overall occurrence rate of Pc3-5 wave events is lowest in summer,
which suggests that the ionospheric conductivity plays a role in controlling ULF
wave occurrence.
PMID- 29938157
TI - Extractive purification of recombinant thermostable lipase from fermentation
broth of Escherichia coli using an aqueous polyethylene glycol impregnated resin
system.
AB - This study aimed at recovery of thermostable lipase from Escherichia coli BL21
using porous glass beads grafted with polyethylene glycol (PEG) in aqueous
impregnated resins system (AIRS). The influencing parameters such as
concentration and pH of extraction solution, concentration of NaCl, size of the
beads, and pH of the desorption solution on the partition behaviour of lipase
were evaluated. Smaller adsorbent (4 mm) had a 65.5% of recovery yield with
approximately two-fold higher purification factor compared to that obtained with
the larger adsorbent. Recombinant lipase was purified successfully using AIRS
with a purification factor of 7.6 and yield of 78.4% under optimum conditions of
18% (w/w) PEG 4000, 10% (w/w) of potassium citrate at pH 9 with 3% (w/w) of NaCl.
Optimum desorption was obtained with 4.0 mm of porous glass beads at pH 9.
PMID- 29938158
TI - A Multiple Stimuli-Sensitive Low-Molecular-Weight Gel with an Aggregate-Induced
Emission Effect for Sol-Gel Transition Detection.
AB - A low-molecular-weight gel (LMWG) with a hydrazone moiety and an aggregate
induced emission (AIE) unit was fabricated; the self-assembly and disassembly of
the LMWG under different stimuli conditions were studied. The LMWG exhibited
multiple stimuli sensitivity with temperature, light, ions, and ionic strength.
The hydrazone was integrated into the gelator to act as ion sensing sites and
hydrogen bond donor groups to fulfil the task of ion recognition of Ni2+, BH4-,
and OH-, as well as ion-controlled reversible sol-gel recovery by adding H+ for
deprotonation; it also broke under UV irradiation to evoke light-sensitivity. In
addition, the sol-gel transition of the gel was detected by the AIE effect. The
research provided an effective strategy in fabricating multiple stimuli-sensitive
LMWGs for potential biomedical applications.
PMID- 29938160
TI - Memory of Chirality as a Prominent Pathway for the Synthesis of Natural Products
through Chiral Intermediates.
AB - The ability of a chiral molecule to be able to transform from one structure to
another, whilst remembering its original molecular information by means of an
appropriate transition state is an abstract notion that may very well play a key
role in important synthetic processes, and has thus attracted a considerable
amount of attention among the chemistry community. Here, we have highlighted this
concept of "memory of chirality" (MOC) and extended it beyond the case of a
simple molecule to larger and more complex natural products. Updated approaches
that have recently been elucidated to obtain these asymmetric natural products
are described, some of which may, until now, have been overcomplicated or
overlooked.
PMID- 29938159
TI - Hydrogen Bonding Regulates the Rigidity of Liposome-Encapsulated Chlorin
Photosensitizers.
AB - Liposomal formulations facilitate the administration of hydrophobic drugs,
avoiding precipitation and aggregation phenomena when injected in polar solvents.
The integration of the photosensitizer into the liposome may alter the fluidity
of the system and, thus, modify the delivery process of the drug. Such a change
has been observed for the liposomal formulation of Temoporfin, which is one of
the most potent chlorin photosensitizers employed in photodynamic therapy. Here,
all-atom molecular dynamics simulations have been performed to identify the
nature of the intermolecular interactions that might be responsible of the
different lipids freedom of motion when the drug is introduced in the bilayer. It
is found that Temoporfin participates as a hydrogen donor in strong hydrogen
bonding interactions with the polar groups of the phospholipids. The theoretical
analysis suggests that the rigidity of drug/liposome complexes can be modulated
by considering the different hydrogen-bond ability of the photosensitizer and the
carrier material.
PMID- 29938161
TI - Mechanical Energy Harvesting Performance of Ferroelectric Polymer Nanowires Grown
via Template-Wetting.
AB - Nanowires of the ferroelectric co-polymer poly(vinylidenefluoride-co
triufloroethylene) [P(VDF-TrFE)] are fabricated from solution within nanoporous
templates of both "hard" anodic aluminium oxide (AAO) and "soft" polyimide (PI)
through a facile and scalable template-wetting process. The confined geometry
afforded by the pores of the templates leads directly to highly crystalline P(VDF
TrFE) nanowires in a macroscopic "poled" state that precludes the need for
external electrical poling procedure typically required for piezoelectric
performance. The energy-harvesting performance of nanogenerators based on these
template-grown nanowires are extensively studied and analyzed in combination with
finite element modelling. Both experimental results and computational models
probing the role of the templates in determining overall nanogenerator
performance, including both materials and device efficiencies, are presented. It
is found that although P(VDF-TrFE) nanowires grown in PI templates exhibit a
lower material efficiency due to lower crystallinity as compared to nanowires
grown in AAO templates, the overall device efficiency was higher for the PI
template-based nanogenerator because of the lower stiffness of the PI template as
compared to the AAO template. This work provides a clear framework to assess the
energy conversion efficiency of template-grown piezoelectric nanowires and paves
the way towards optimization of template-based nanogenerator devices.
PMID- 29938162
TI - Nanofabricated Ultraflexible Electrode Arrays for High-Density Intracortical
Recording.
AB - Understanding brain functions at the circuit level requires time-resolved
simultaneous measurement of a large number of densely distributed neurons, which
remains a great challenge for current neural technologies. In particular,
penetrating neural electrodes allow for recording from individual neurons at high
temporal resolution, but often have larger dimensions than the biological matrix,
which induces significant damage to brain tissues and therefore precludes the
high implant density that is necessary for mapping large neuronal populations
with full coverage. Here, it is demonstrated that nanofabricated ultraflexible
electrode arrays with cross-sectional areas as small as sub-10 um2 can overcome
this physical limitation. In a mouse model, it is shown that these electrodes
record action potentials with high signal-to-noise ratio; their dense arrays
allow spatial oversampling; and their multiprobe implantation allows for
interprobe spacing at 60 um without eliciting chronic neuronal degeneration.
These results present the possibility of minimizing tissue displacement by
implanted ultraflexible electrodes for scalable, high-density
electrophysiological recording that is capable of complete neuronal circuitry
mapping over chronic time scales.
PMID- 29938163
TI - Hard X-Ray Nanoholotomography: Large-Scale, Label-Free, 3D Neuroimaging beyond
Optical Limit.
AB - There have been great efforts on the nanoscale 3D probing of brain tissues to
image subcellular morphologies. However, limitations in terms of tissue coverage,
anisotropic resolution, stain dependence, and complex sample preparation all
hinder achieving a better understanding of the human brain functioning in the
subcellular context. Herein, X-ray nanoholotomography is introduced as an
emerging synchrotron radiation-based technology for large-scale, label-free,
direct imaging with isotropic voxel sizes down to 25 nm, exhibiting a spatial
resolution down to 88 nm. The procedure is nondestructive as it does not require
physical slicing. Hence, it allows subsequent imaging by complementary
techniques, including histology. The feasibility of this 3D imaging approach is
demonstrated on human cerebellum and neocortex specimens derived from paraffin
embedded tissue blocks. The obtained results are compared to hematoxylin and
eosin stained histological sections and showcase the ability for rapid
hierarchical neuroimaging and automatic rebuilding of the neuronal architecture
at the level of a single cell nucleolus. The findings indicate that
nanoholotomography can complement microscopy not only by large isotropic
volumetric data but also by morphological details on the sub-100 nm level,
addressing many of the present challenges in brain tissue characterization and
probably becoming an important tool in nanoanatomy.
PMID- 29938164
TI - Tailoring Surface Frustrated Lewis Pairs of In2O3-x (OH)y for Gas-Phase
Heterogeneous Photocatalytic Reduction of CO2 by Isomorphous Substitution of In3+
with Bi3.
AB - Frustrated Lewis pairs (FLPs) created by sterically hindered Lewis acids and
Lewis bases have shown their capacity for capturing and reacting with a variety
of small molecules, including H2 and CO2, and thereby creating a new strategy for
CO2 reduction. Here, the photocatalytic CO2 reduction behavior of defect-laden
indium oxide (In2O3-x (OH) y ) is greatly enhanced through isomorphous
substitution of In3+ with Bi3+, providing fundamental insights into the
catalytically active surface FLPs (i.e., In-OH...In) and the experimentally
observed "volcano" relationship between the CO production rate and Bi3+
substitution level. According to density functional theory calculations at the
optimal Bi3+ substitution level, the 6s2 electron pair of Bi3+ hybridizes with
the oxygen in the neighboring In-OH Lewis base site, leading to mildly increased
Lewis basicity without influencing the Lewis acidity of the nearby In Lewis acid
site. Meanwhile, Bi3+ can act as an extra acid site, serving to maximize the
heterolytic splitting of reactant H2, and results in a more hydridic hydride for
more efficient CO2 reduction. This study demonstrates that isomorphous
substitution can effectively optimize the reactivity of surface catalytic active
sites in addition to influencing optoelectronic properties, affording a better
understanding of the photocatalytic CO2 reduction mechanism.
PMID- 29938165
TI - Acorn Barnacles Secrete Phase-Separating Fluid to Clear Surfaces Ahead of Cement
Deposition.
AB - Marine macrofoulers (e.g., barnacles, tubeworms, mussels) create underwater
adhesives capable of attaching themselves to almost any material. The difficulty
in removing these organisms frustrates maritime and oceanographic communities,
and fascinates biomedical and industrial communities seeking synthetic adhesives
that cure and hold steadfast in aqueous environments. Protein analysis can reveal
the chemical composition of natural adhesives; however, developing synthetic
analogs that mimic their performance remains a challenge due to an incomplete
understanding of adhesion processes. Here, it is shown that acorn barnacles
(Amphibalanus (=Balanus) amphitrite) secrete a phase-separating fluid ahead of
growth and cement deposition. This mixture consists of a phenolic laden
gelatinous phase that presents a phase rich in lipids and reactive oxygen species
at the seawater interface. Nearby biofilms rapidly oxidize and lift off the
surface as the secretion advances. While phenolic chemistries are ubiquitous to
arthropod adhesives and cuticles, the findings demonstrate that A. amphitrite
uses these chemistries in a complex surface-cleaning fluid, at a substantially
higher relative abundance than in its adhesive. The discovery of this critical
step in underwater adhesion represents a missing link between natural and
synthetic adhesives, and provides new directions for the development of
environmentally friendly biofouling solutions.
PMID- 29938166
TI - Fever-Inspired Immunotherapy Based on Photothermal CpG Nanotherapeutics: The
Critical Role of Mild Heat in Regulating Tumor Microenvironment.
AB - Although there have been more than 100 clinical trials, CpG-based immunotherapy
has been seriously hindered by complications in the immunosuppressive
microenvironment of established tumors. Inspired by the decisive role of fever
upon systemic immunity, a photothermal CpG nanotherapeutics (PCN) method with the
capability to induce an immunofavorable tumor microenvironment by casting a fever
relevant heat (43 degrees C) in the tumor region is developed. High-throughput
gene profile analysis identifies nine differentially expressed genes that are
closely immune-related upon mild heat, accompanied by IL-6 upregulation, a
pyrogenic cytokine usually found during fever. When treated with intratumor PCN
injection enabling mild heating in the tumor region, the 4T1 tumor-bearing mice
exhibit significantly improved antitumor immune effects compared with the control
group. Superb efficacy is evident from pronounced apoptotic cell death, activated
innate immune cells, enhanced tumor perfusion, and intensified innate and
adaptive immune responses. This work highlights the crucial role of mild heat in
modulating the microenvironment in optimum for improved immunotherapy, by
converting the tumor into an in situ vaccine.
PMID- 29938167
TI - Tailoring TiO2 Nanotube-Interlaced Graphite Carbon Nitride Nanosheets for
Improving Visible-Light-Driven Photocatalytic Performance.
AB - Rapid recombination of photoinduced electron-hole pairs is one of the major
defects in graphitic carbon nitride (g-C3N4)-based photocatalysts. To address
this issue, perforated ultralong TiO2 nanotube-interlaced g-C3N4 nanosheets
(PGCN/TNTs) are prepared via a template-based process by treating g-C3N4 and TiO2
nanotubes polymerized hybrids in alkali solution. Shortened migration distance of
charge transfer is achieved from perforated PGCN/TNTs on account of cutting
redundant g-C3N4 nanosheets, leading to subdued electron-hole recombination. When
PGCN/TNTs are employed as photocatalysts for H2 generation, their in-plane holes
and high hydrophilicity accelerate cross-plane diffusion to dramatically promote
the photocatalytic reaction in kinetics and supply plentiful catalytic active
centers. By having these unique features, PGCN/TNTs exhibit superb visible-light
H2-generation activity of 1364 umol h-1 g-1 (lambda > 400 nm) and a notable
quantum yield of 6.32% at 420 nm, which are much higher than that of bulk g-C3N4
photocatalysts. This study demonstrates an ingenious design to weaken the
electron recombination in g-C3N4 for significantly enhancing its photocatalytic
capability.
PMID- 29938168
TI - Green-Light-Activated Photoreaction via Genetic Hybridization of Far-Red
Fluorescent Protein and Silk.
AB - Fluorescent proteins often result in phototoxicity and cytotoxicity, in
particular because some red fluorescent proteins produce and release reactive
oxygen species (ROS). The photogeneration of ROS is considered as a detrimental
side effect in cellular imaging or is proactively utilized for ablating cancerous
tissue. As ancient textiles or biomaterials, silk produced by silkworms can
directly be used as fabrics or be processed into materials and structures to host
other functional nanomaterials. It is reported that transgenic fusion of far-red
fluorescent protein (mKate2) with silk provides a photosensitizer hybridization
platform for photoinducible control of ROS. Taking advantage of green (visible)
light activation, native and regenerated mKate2 silk can produce and release
superoxide and singlet oxygen, in a comparable manner of visible light-driven
plasmonic photocatalysis. Thus, the genetic expression of mKate2 in silk offers
immediately exploitable and scalable photocatalyst-like biomaterials. It is
further envisioned that mKate2 silk can potentially rule out hazardous concerns
associated with foreign semiconductor photocatalytic nanomaterials.
PMID- 29938169
TI - Laminated Hybrid Junction of Sulfur-Doped TiO2 and a Carbon Substrate Derived
from Ti3C2 MXenes: Toward Highly Visible Light-Driven Photocatalytic Hydrogen
Evolution.
AB - TiO2 is an ideal photocatalyst candidate except for its large bandgap and fast
charge recombination. A novel laminated junction composed of defect-controlled
and sulfur-doped TiO2 with carbon substrate (LDC-S-TiO2/C) is synthesized using
the 2D transition metal carbides (MXenes) as a template to enhance light
absorption and improve charge separation. The prepared LDC-S-TiO2/C catalyst
delivers a high photocatalytic H2 evolution rate of 333 umol g-1 h-1 with a high
apparent quantum yield of 7.36% at 400 nm and it is also active even at 600 nm,
resulting into a 48 time activity compared with L-TiO2/C under visible light
irradiation. Further theoretical modeling calculation indicates that such novel
approach also reduces activation energy of hydrogen production apart from
broadening the absorption wavelength, facilitating charge separation, and
creating a large surface area substrate. This synergic effect can also be applied
to other photocatalysts' modification. The study provides a novel approach for
synthesis defective metal oxides based hybrids and broaden the applications of
MXene family.
PMID- 29938170
TI - Painful Terminal Neuroma Prevention by Capping PRGD/PDLLA Conduit in Rat Sciatic
Nerves.
AB - Neuroma formation after amputation as a long-term deficiency leads to spontaneous
neuropathic pain that reduces quality of life of patients. To prevent neuroma
formation, capping techniques are implemented as effective treatments. However,
an ideal, biocompatible material covering the nerves is an unmet clinical need.
In this study, biocompatible characteristics presented by the poly(D,L-lactic
acid)/arginylglycylaspartic acid (RGD peptide) modification of poly{(lactic acid)
co- [(glycolic acid)-alt-(L-lysine)]} (PRGD/PDLLA) are evaluated as a nerve
conduit. After being capped on the rat sciatic nerve stump in vivo, rodent
behaviors and tissue structures are compared via autotomy scoring and
histological analyses. The PRGD/PDLLA capped group gains lower autotomy score and
improves the recovery, where inflammatory infiltrations and excessive collagen
deposition are defeated. Transmission electron microscopy images of the
regeneration of myelin sheath in both groups show that abnormal myelination is
only present in the uncapped rats. Changes in related genes (MPZ, MBP, MAG, and
Krox20) are monitored quantitative real-time polymerase chain reaction (qRT-PCR)
for mechanism investigation. The PRGD/PDLLA capping conduits not only act as
physical barriers to inhibit the invasion of inflammatory infiltration in the
scar tissue but also provide a suitable microenvironment for promoting nerve
repairing and avoiding neuroma formation during nerve recovery.
PMID- 29938171
TI - Room-Temperature Nanoseconds Spin Relaxation in WTe2 and MoTe2 Thin Films.
AB - The Weyl semimetal WTe2 and MoTe2 show great potential in generating large spin
currents since they possess topologically protected spin-polarized states and can
carry a very large current density. In addition, the intrinsic non-centrosymmetry
of WTe2 and MoTe2 endows with a unique property of crystal symmetry-controlled
spin-orbit torques. An important question to be answered for developing
spintronic devices is how spins relax in WTe2 and MoTe2. Here, a room-temperature
spin relaxation time of 1.2 ns (0.4 ns) in WTe2 (MoTe2) thin film using the time
resolved Kerr rotation (TRKR) is reported. Based on ab initio calculation, a
mechanism of long-lived spin polarization resulting from a large spin splitting
around the bottom of the conduction band, low electron-hole recombination rate,
and suppression of backscattering required by time-reversal and lattice symmetry
operation is identified. In addition, it is found that the spin polarization is
firmly pinned along the strong internal out-of-plane magnetic field induced by
large spin splitting. This work provides an insight into the physical origin of
long-lived spin polarization in Weyl semimetals, which could be useful to
manipulate spins for a long time at room temperature.
PMID- 29938172
TI - Advanced GeSn/SiGeSn Group IV Heterostructure Lasers.
AB - Growth and characterization of advanced group IV semiconductor materials with
CMOS-compatible applications are demonstrated, both in photonics. The
investigated GeSn/SiGeSn heterostructures combine direct bandgap GeSn active
layers with indirect gap ternary SiGeSn claddings, a design proven its worth
already decades ago in the III-V material system. Different types of double
heterostructures and multi-quantum wells (MQWs) are epitaxially grown with
varying well thicknesses and barriers. The retaining high material quality of
those complex structures is probed by advanced characterization methods, such as
atom probe tomography and dark-field electron holography to extract composition
parameters and strain, used further for band structure calculations. Special
emphasis is put on the impact of carrier confinement and quantization effects,
evaluated by photoluminescence and validated by theoretical calculations. As
shown, particularly MQW heterostructures promise the highest potential for
efficient next generation complementary metal-oxide-semiconductor (CMOS)
compatible group IV lasers.
PMID- 29938173
TI - Trojan-Horse-Like Stimuli-Responsive Microcapsules.
AB - Multicompartment microcapsules, with each compartment protected by a distinct
stimuli-responsive shell for versatile controlled release, are highly desired for
developing new-generation microcarriers. Although many multicompartmental
microcapsules have been created, most cannot combine different release styles to
achieve flexible programmed sequential release. Here, one-step template synthesis
of controllable Trojan-horse-like stimuli-responsive microcapsules is reported
with capsule-in-capsule structures from microfluidic quadruple emulsions for
diverse programmed sequential release. The nested inner and outer capsule
compartments can separately encapsulate different contents, while their two
stimuli-responsive hydrogel shells can individually control the content release
from each capsule compartment for versatile sequential release. This is
demonstrated by using three types of Trojan-horse-like stimuli-responsive
microcapsules, with different combinations of release styles for flexible
programmed sequential release. The proposed microcapsules provide novel advanced
candidates for developing new-generation microcarriers for diverse, efficient
applications.
PMID- 29938174
TI - How Low Nucleation Density of Graphene on CuNi Alloy is Achieved.
AB - CuNi alloy foils are demonstrated to be one of the best substrates for
synthesizing large area single-crystalline graphene because a very fast growth
rate and low nucleation density can be simultaneously achieved. The fast growth
rate is understood to be due the abundance of carbon precursor supply, as a
result of the high catalytic activity of Ni atoms. However, a theoretical
understanding of the low nucleation density remains controversial because it is
known that a high carbon precursor concentration on the surface normally leads to
a high nucleation density. Here, the graphene nucleation on the CuNi alloy
surfaces is systematically explored and it is revealed that: i) carbon atom
dissolution into the CuNi alloy passivates the alloy surface, thereby drastically
increasing the graphene nucleation barrier; ii) carbon atom diffusion on the CuNi
alloy surface is greatly suppressed by the inhomogeneous atomic structure of the
surface; and iii) a prominent increase in the rate of carbon diffusion into the
bulk occurs when the Ni composition is higher than the percolation threshold.
This study reveals the key mechanism for graphene nucleation on CuNi alloy
surfaces and provides a guideline for the catalyst design for the synthesis of
graphene and other 2D materials.
PMID- 29938176
TI - FeO x -Based Materials for Electrochemical Energy Storage.
AB - Iron oxides (FeO x ), such as Fe2O3 and Fe3O4 materials, have attracted much
attention because of their rich abundance, low cost, and environmental
friendliness. However, FeO x , which is similar to most transition metal oxides,
possesses a poor rate capability and cycling life. Thus, FeO x -based materials
consisting of FeO x , carbon, and metal-based materials have been widely
explored. This article mainly discusses FeO x -based materials (Fe2O3 and Fe3O4)
for electrochemical energy storage applications, including supercapacitors and
rechargeable batteries (e.g., lithium-ion batteries and sodium-ion batteries).
Furthermore, future perspectives and challenges of FeO x -based materials for
electrochemical energy storage are briefly discussed.
PMID- 29938177
TI - Triazatruxene: A Rigid Central Donor Unit for a D-A3 Thermally Activated Delayed
Fluorescence Material Exhibiting Sub-Microsecond Reverse Intersystem Crossing and
Unity Quantum Yield via Multiple Singlet-Triplet State Pairs.
AB - By inverting the common structural motif of thermally activated delayed
fluorescence materials to a rigid donor core and multiple peripheral acceptors,
reverse intersystem crossing (rISC) rates are demonstrated in an organic material
that enables utilization of triplet excited states at faster rates than Ir-based
phosphorescent materials. A combination of the inverted structure and multiple
donor-acceptor interactions yields up to 30 vibronically coupled singlet and
triplet states within 0.2 eV that are involved in rISC. This gives a significant
enhancement to the rISC rate, leading to delayed fluorescence decay times as low
as 103.9 ns. This new material also has an emission quantum yield ~1 and a very
small singlet-triplet gap. This work shows that it is possible to achieve both
high photoluminescence quantum yield and fast rISC in the same molecule. Green
organic light-emitting diode devices with external quantum efficiency >30% are
demonstrated at 76 cd m-2.
PMID- 29938175
TI - Application of the CRISPR/Cas9 System to Drug Resistance in Breast Cancer.
AB - Clinical evidence indicates that drug resistance is a great obstacle in breast
cancer therapy. It renders the disease uncontrollable and causes high mortality.
Multiple mechanisms contribute to the development of drug resistance, but the
underlying cause is usually a shift in the genetic composition of tumor cells. It
is increasingly feasible to engineer the genome with the clustered regularly
interspaced short palindromic repeats (CRISPR)/associated (Cas)9 technology
recently developed, which might be advantageous in overcoming drug resistance.
This article discusses how the CRISPR/Cas9 system might revert resistance gene
mutations and identify potential resistance targets in drug-resistant breast
cancer. In addition, the challenges that impede the clinical applicability of
this technology and highlight the CRISPR/Cas9 systems are presented. The
CRISPR/Cas9 system is poised to play an important role in preventing drug
resistance in breast cancer therapy and will become an essential tool for
personalized medicine.
PMID- 29938178
TI - In Situ Atomic-Scale Study of Particle-Mediated Nucleation and Growth in
Amorphous Bismuth to Nanocrystal Phase Transformation.
AB - Understanding classical and nonclassical mechanisms of crystal nucleation and
growth at the atomic scale is of great interest to scientists in many
disciplines. However, fulfilling direct atomic-scale observation still poses a
significant challenge. Here, by taking a thin amorphous bismuth (Bi) metal
nanosheet as a model system, direct atomic resolution of the crystal nucleation
and growth initiated from an amorphous state of Bi metal under electron beam
inside an aberration-corrected transmission electron microscope is provided. It
is shown that the crystal nucleation and growth in the phase transformation of Bi
metal from amorphous to crystalline structure takes place via the particle
mediated nonclassical mechanism instead of the classical atom-mediated mechanism.
The dimension of the smaller particles in two contacted nanoparticles and their
mutual orientation relationship are critical to governing several coalescence
pathways: total rearrangement pathway, grain boundary migration-dominated
pathway, and surface migration-dominated pathway. Sequential strain analyses
imply that migration of the grain boundary is driven by the strain difference in
two Bi nanocrystals and the coalescence of nanocrystals is a defect reduction
process. The findings may provide useful information to clarify the nanocrystal
growth mechanisms of other materials on the atomic scale.
PMID- 29938179
TI - Primitive Photosynthetic Architectures Based on Self-Organization and Chemical
Evolution of Amino Acids and Metal Ions.
AB - The emergence of light-energy-utilizing metabolism is likely to be a critical
milestone in prebiotic chemistry and the origin of life. However, how the
primitive pigment is spontaneously generated still remains unknown. Herein, a
primitive pigment model based on adaptive self-organization of amino acids
(Cystine, Cys) and metal ions (zinc ion, Zn2+) followed by chemical evolution
under hydrothermal conditions is developed. The resulting hybrid microspheres are
composed of radially aligned cystine/zinc (Cys/Zn) assembly decorated with
carbonate-doped zinc sulfide (C-ZnS) nanocrystals. The part of C-ZnS can work as
a light-harvesting antenna to capture ultraviolet and visible light, and use it
in various photochemical reactions, including hydrogen (H2) evolution, carbon
dioxide (CO2) photoreduction, and reduction of nicotinamide adenine dinucleotide
(NAD+) to nicotinamide adenine dinucleotide hydride (NADH). Additionally, guest
molecules (e.g., glutamate dehydrogenase, GDH) can be encapsulated within the
hierarchical Cys/Zn framework, which facilitates sustainable photoenzymatic
synthesis of glutamate. This study helps deepen insight into the emergent
functionality (conversion of light energy) and complexity (hierarchical
architecture) from interaction and reaction of prebiotic molecules. The primitive
pigment model is also promising to work as an artificial photosynthetic
microreactor.
PMID- 29938180
TI - Microstructured Elastomer-PEG Hydrogels via Kinetic Capture of Aqueous Liquid
Liquid Phase Separation.
AB - Heterogeneous hydrogels with desired matrix complexity are studied for a variety
of biomimetic materials. Despite the range of such microstructured materials
described, few methods permit independent control over microstructure and
microscale mechanics by precisely controlled, single-step processing methods.
Here, a phototriggered crosslinking methodology that traps microstructures in
liquid-liquid phase-separated solutions of a highly elastomeric resilin-like
polypeptide (RLP) and poly(ethylene glycol) (PEG) is reported. RLP-rich domains
of various diameters can be trapped in a PEG continuous phase, with the kinetics
of domain maturation dependent on the degree of acrylation. The chemical
composition of both hydrogel phases over time is assessed via in situ
hyperspectral coherent Raman microscopy, with equilibrium concentrations
consistent with the compositions derived from NMR-measured coexistence curves.
Atomic force microscopy reveals that the local mechanical properties of the two
phases evolve over time, even as the bulk modulus of the material remains
constant, showing that the strategy permits control of mechanical properties on
micrometer length scales, of relevance in generating mechanically robust
materials for a range of applications. As one example, the successful
encapsulation, localization, and survival of primary cells are demonstrated and
suggest the potential application of phase-separated RLP-PEG hydrogels in
regenerative medicine applications.
PMID- 29938182
TI - Smart Surgical Catheter for C-Reactive Protein Sensing Based on an Imperceptible
Organic Transistor.
AB - Organic field-effect transistors (OFETs)-based sensors have a great potential to
be integrated with the next generation smart surgical tools for monitoring
different real-time signals during surgery. However, allowing ultraflexible OFETs
to have compatibility with standard medical sterilization procedures remains
challenging. A novel capsule-like OFET structure is demonstrated by utilizing the
fluoropolymer CYTOP to serve both encapsulation and peeling-off enhancement
purposes. By adapting a thermally stable organic semiconductor, 2,10
diphenylbis[1]benzothieno[2,3-d;2',3'-d']naphtho[2,3-b;6,7-b']dithiophene (DPh
BBTNDT), these devices show excellent stability in their electrical performance
after sterilizing under boiling water and 100 degrees C-saturated steam for 30
min. The ultrathin thickness (630 nm) enables the device to have superb
mechanical flexibility with smallest bending radius down to 1.5 um, which is
essential for application on the highly tortuous medical catheter inside the
human body. By immobilizing anti-human C-reactive protein (CRP) (an inflammation
biomarker) monoclonal antibody on an extended gate of the OFET, a sensitivity for
detecting CRP antigen down to 1 ug mL-1 can be achieved. An ecofriendly water
floatation method realized by employing the wettability difference between CYTOP
and polyacrylonitrile (PAN) can be used to transfer the device on a ventricular
catheter, which successfully distinguishes an inflammatory patient from a healthy
one.
PMID- 29938181
TI - Progress and Promise of Nitric Oxide-Releasing Platforms.
AB - Nitric oxide (NO) is a highly potent radical with a wide spectrum of
physiological activities. Depending on the concentration, it can enhance
endothelial cell proliferation in a growth factor-free medium, mediate
angiogenesis, accelerate wound healing, but may also lead to tumor progression or
induce inflammation. Due to its multifaceted role, NO must be administered at a
right dose and at the specific site. Many efforts have focused on developing NO
releasing biomaterials; however, NO short half-life in human tissues only allows
this molecule to diffuse over short distances, and significant challenges remain
before the full potential of NO can be realized. Here, an overview of platforms
that are engineered to release NO via catalytic or noncatalytic approaches is
presented, with a specific emphasis on progress reported in the past five years.
A number of NO donors, natural enzymes, and enzyme mimics are highlighted, and
recent promising developments of NO-releasing scaffolds, particles, and films are
presented. In particular, key parameters of NO delivery are discussed: 1) NO
payload, 2) maximum NO flux, 3) NO release half-life, 4) time required to reach
maximum flux, and 5) duration of NO release. Advantages and drawbacks are
reviewed, and possible further developments are suggested.
PMID- 29938183
TI - Mucoadhesive Cationic Polypeptide Nanogel with Enhanced Penetration for Efficient
Intravesical Chemotherapy of Bladder Cancer.
AB - Initially, chemotherapy is effective for treatment of bladder cancer after
transurethral resection of the bladder. However, certain patients progressively
become unresponsive after multiple treatment cycles, which results from the rapid
and almost complete excretion of clinically used formulations of antineoplastic
agents with urinary voiding. Improving the mucoadhesiveness and penetrability of
chemotherapeutic drugs are key factors in treatment of advanced bladder cancer.
Here, a smart disulfide-crosslinked polypeptide nanogel of poly(l-lysine)-poly(l
phenylalanine-co-l-cystine) (PLL-P(LP-co-LC)) is developed to deliver 10
hydroxycamptothecin (HCPT) for treatment of orthotopic bladder cancer. The
positively charged PLL-P(LP-co-LC) can significantly prolong the retention period
and enhance the tissue permeability of HCPT within the bladder wall of rat.
Moreover, the reduction-responsive polypeptide nanogel (i.e., NG/HCPT) possesses
the capability to accurately and rapidly deliver HCPT in bladder cancer cells.
NG/HCPT can significantly inhibit proliferation of human bladder cancer 5637
cells in vitro and enhance antitumor activity toward an orthotopic rat bladder
cancer model in vivo. This work demonstrates that the smart polypeptide nanogel
may function as a promising drug-delivery system for local chemotherapy of
bladder cancer with unprecedented clinical benefits.
PMID- 29938184
TI - Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment-Responsive Drug
Delivery System for Targeted Cancer Therapy.
AB - The tumor microenvironment (TME) plays a crucial role in tumorigenesis and cancer
cell metastasis. Accordingly, a drug-delivery system (DDS) that is capable of
targeting tumor and releasing drugs in response to TME-associated stimuli should
lead to potent antitumor efficacy. Here, a cancer targeting, reactive oxygen
species (ROS)-responsive drug delivery vehicle as an example of a TME-targeting
DDS is reported. Tumor targeting is achieved using biotin as a ligand for "biotin
transporter"-overexpressing malignant tumors, and bilirubin-based nanoparticles
(BRNPs) are used as a drug-delivery carrier that enables ROS-responsive drug
release. Doxorubicin-loaded, biotinylated BRNPs (Dox@bt-BRNPs) with size of ~100
nm are prepared by a one-step self-assembly process. Dox@bt-BRNPs exhibit
accelerated Dox-release behavior in response to ROS and show specific binding as
well as anticancer activity against biotin transporter-overexpressing HeLa cells
in vitro. bt-BRNPs labeled with cypate, near-infrared dye, show much greater
accumulation at tumor sites in HeLa tumor-bearing mice than BRNPs lacking the
biotin ligand. Finally, intravenous injection of Dox@bt-BRNPs into HeLa tumor
bearing mice results in greater antitumor efficacy compared with free Dox, bt
BRNPs only, and Dox@BRNPs without causing any appreciable body weight loss.
Collectively, these findings suggest that bt-BRNPs hold potential as a new TME
responsive DDS for effectively treating various tumors.
PMID- 29938185
TI - Compartmentalized Microhelices Prepared via Electrohydrodynamic Cojetting.
AB - Anisotropically compartmentalized microparticles have attracted increasing
interest in areas ranging from sensing, drug delivery, and catalysis to
microactuators. Herein, a facile method is reported for the preparation of
helically decorated microbuilding blocks, using a modified electrohydrodynamic
cojetting method. Bicompartmental microfibers are twisted in situ, during
electrojetting, resulting in helical microfibers. Subsequent cryosectioning of
aligned fiber bundles provides access to helically decorated microcylinders. The
unique helical structure endows the microfibers/microcylinders with several novel
functions such as translational motion in response to rotating magnetic fields.
Finally, microspheres with helically patterned compartments are obtained after
interfacially driven shape shifting of helically decorated microcylinders.
PMID- 29938186
TI - 3D Visible-Light Invisibility Cloak.
AB - The concept of an invisibility cloak is a fixture of science fiction, fantasy,
and the collective imagination. However, a real device that can hide an object
from sight in visible light from absolutely any viewpoint would be extremely
challenging to build. The main obstacle to creating such a cloak is the coupling
of the electromagnetic components of light, which would necessitate the use of
complex materials with specific permittivity and permeability tensors. Previous
cloaking solutions have involved circumventing this obstacle by functioning
either in static (or quasistatic) fields where these electromagnetic components
are uncoupled or in diffusive light scattering media where complex materials are
not required. In this paper, concealing a large-scale spherical object from human
sight from three orthogonal directions is reported. This result is achieved by
developing a 3D homogeneous polyhedral transformation and a spatially invariant
refractive index discretization that considerably reduce the coupling of the
electromagnetic components of visible light. This approach allows for a major
simplification in the design of 3D invisibility cloaks, which can now be created
at a large scale using homogeneous and isotropic materials.
PMID- 29938187
TI - Multidimensional Evolution of Carbon Structures Underpinned by Temperature
Induced Intermediate of Chloride for Sodium-Ion Batteries.
AB - Different dimensions of carbon materials with various features have captured
numerous interests due to their applications on the tremendous fields. Restricted
by the raw materials and devices, the controlling of their morphology is a major
challenge. Utilizing the catalytic features of the intermediates from the low
cost salts and polymerization of 0D carbon quantum dots (CQDs), 0D CQDs are
expected to self-assemble into 1/2/3D carbon structures with the assistance of
temperature-induced intermediates (e.g., ZnO, Ni, and Cu) from the salts (ZnCl2,
NiCl2, and CuCl). The formation mechanisms are illustrated as follows: 1) the
"orient induction" to evoke "vine style" growth mechanism of ZnO; 2) the
"dissolution-precipitation" of Ni; and 3) the "surface adsorption self-limited"
of Cu. Subsequently, the degree of graphitization, interlayer distance, and
special surface area are investigated in detail. 1D structure from 700 degrees C
as anode displays a high Na-storage capacity of 301.2 mAh g-1 at 0.1 A g-1 after
200 cycles and 107 mAh g-1 at 5.0 A g-1 after 5000 cycles. Quantitative kinetics
analysis confirms the fundamentals of the enhanced rate capacity and the
potential region of Na-insertion/extraction. This elaborate work opens up an
avenue toward the design of carbon with multidimensions and in-depth
understanding of their sodium-storage features.
PMID- 29938188
TI - Atomic Scale Modulation of Self-Rectifying Resistive Switching by Interfacial
Defects.
AB - Higher memory density and faster computational performance of resistive switching
cells require reliable array-accessible architecture. However, selecting a
designated cell within a crossbar array without interference from sneak path
currents through neighboring cells is a general problem. Here, a highly doped n++
Si as the bottom electrode with Ni-electrode/HfO x /SiO2 asymmetric self
rectifying resistive switching device is fabricated. The interfacial defects in
the HfO x /SiO2 junction and n++ Si substrate result in the reproducible
rectifying behavior. In situ transmission electron microscopy is used to
quantitatively study the properties of the morphology, chemistry, and dynamic
nucleation-dissolution evolution of the chains of defects at the atomic scale.
The spatial and temporal correlation between the concentration of oxygen
vacancies and Ni-rich conductive filament modifies the resistive switching
effect. This study has important implications at the array-level performance of
high density resistive switching memories.
PMID- 29938189
TI - Efficient Planar Perovskite Solar Cells Using Passivated Tin Oxide as an Electron
Transport Layer.
AB - Planar perovskite solar cells using low-temperature atomic layer deposition (ALD)
of the SnO2 electron transporting layer (ETL), with excellent electron extraction
and hole-blocking ability, offer significant advantages compared with high
temperature deposition methods. The optical, chemical, and electrical properties
of the ALD SnO2 layer and its influence on the device performance are
investigated. It is found that surface passivation of SnO2 is essential to reduce
charge recombination at the perovskite and ETL interface and show that the
fabricated planar perovskite solar cells exhibit high reproducibility, stability,
and power conversion efficiency of 20%.
PMID- 29938190
TI - Uncovering the Binding Specificities of Lectins with Cells for Precision
Colorectal Cancer Diagnosis Based on Multimodal Imaging.
AB - There is a high desire for novel targets/biomarkers to diagnose and treat
colorectal cancer (CRC). Here, an approach starting from a polyacrylamide
hydrogel-based lectin microarray is presented to screen the high expression of
glycans on the CRC cell surface and to identify new lectin biomarkers for CRC.
Three common CRC cell lines (SW480, SW620, and HCT116) and one normal colon cell
line (NCM460) are profiled on the microarray with 27 lectins. The experimental
results reveal that CRC cells highly express the glycans with d-galactose, d
glucose, and/or sialic acid residues, and Uelx Europaeus Agglutinin-I (UEA-I)
exhibits reasonable specificity with SW480 cells. After conjugation of UEA-I with
silica-coated NaGdF4:Yb3+, Er3+@NaGdF4 upconversion nanoparticles, the follow-up
in vitro and in vivo experiments provide further evidence on that UEA-I can serve
as tumor-targeting molecule to diagnose SW480 tumor by multimodal imaging
including upconversion luminescence imaging, T1-weighted magnetic resonance
imaging, and X-ray computed tomography imaging.
PMID- 29938191
TI - In Situ One-Pot Synthesis of MOF-Polydopamine Hybrid Nanogels with Enhanced
Photothermal Effect for Targeted Cancer Therapy.
AB - Herein, a simple one-pot way is designed to prepare a type of multifunctional
metal-organic framework (MOF)-based hybrid nanogels by in situ hybridization of
dopamine monomer in the skeleton of MnCo. The resultant hybrid nanoparticles
(named as MCP) show enhanced photothermal conversion efficiency in comparison
with pure polydopamine or MnCo nanoparticles (NPs) synthesized under a similar
method and, therefore, show great potential for photothermal therapy (PTT) in
vivo. The MCP NPs are expected to possess T1 positive magnetic resonance imaging
ability due to the high-spin Mn-N6 (S = 5/2) in the skeleton of MnCo. To improve
the therapy efficiency as a PTT agent, the MCP NPs are further modified with
functional polyethylene glycol (PEG) and thiol terminal cyclic arginine-glycine
aspartic acid peptide, respectively: the first one is to increase the stability,
biocompatibility, and blood circulation time of MCP NPs in vivo; the second one
is to increase the tumor accumulation of MCP-PEG NPs and improve their
therapeutic efficiency as photothermal agent.
PMID- 29938192
TI - A New Nonfullerene Acceptor with Near Infrared Absorption for High Performance
Ternary-Blend Organic Solar Cells with Efficiency over 13.
AB - A new acceptor-donor-acceptor (A-D-A) type nonfullerene acceptor, 3TT-FIC, which
has three fused thieno[3,2-b]thiophene as the central core and difluoro
substituted indanone as the end groups, is designed and synthesized. 3TT-FIC
exhibits broad and strong absorption with extended onset absorption to 995 nm and
a low optical bandgap of 1.25 eV. The binary device based on 3TT-FIC and the
polymer PTB7-Th exhibits a power conversion efficiency (PCE) of 12.21% with a
high short circuit current density ( Jsc) of 25.89 mA cm-2. To fine-tune the
morphology and make full use of the visible region sunlight, phenyl-C71
butyricacid-methyl ester (PC71BM) is used as the third component to fabricate
ternary devices. In contrast to the binary devices, the ternary blend organic
solar cells show significantly enhanced EQE ranging from 300 to 700 nm and thus
an improved Jsc with a high value of 27.73 mA cm-2. A high PCE with a value of
13.54% is achieved for the ternary devices, which is one of the highest
efficiencies in single junction organic solar cells reported to date. The results
provide valuable insight for the ternary devices in which the external quantum
efficiency (EQE) induced by the third component is evidently observed and
directly contributed to the enhancement of the device efficiency.
PMID- 29938193
TI - A Nacre-Like Carbon Nanotube Sheet for High Performance Li-Polysulfide Batteries
with High Sulfur Loading.
AB - Lithium-sulfur (Li-S) batteries are considered as one of the most promising
energy storage systems for next-generation electric vehicles because of their
high-energy density. However, the poor cyclic stability, especially at a high
sulfur loading, is the major obstacles retarding their practical use. Inspired by
the nacre structure of an abalone, a similar configuration consisting of layered
carbon nanotube (CNT) matrix and compactly embedded sulfur is designed as the
cathode for Li-S batteries, which are realized by a well-designed unidirectional
freeze-drying approach. The compact and lamellar configuration with closely
contacted neighboring CNT layers and the strong interaction between the highly
conductive network and polysulfides have realized a high sulfur loading with
significantly restrained polysulfide shuttling, resulting in a superior cyclic
stability and an excellent rate performance for the produced Li-S batteries.
Typically, with a sulfur loading of 5 mg cm-2, the assembled batteries
demonstrate discharge capacities of 1236 mAh g-1 at 0.1 C, 498 mAh g-1 at 2 C and
moreover, when the sulfur loading is further increased to 10 mg cm-2 coupling
with a carbon-coated separator, a superhigh areal capacity of 11.0 mAh cm-2 is
achieved.
PMID- 29938194
TI - Erratum: Self-Stabilized Hyaluronate Nanogel for Intracellular Codelivery of
Doxorubicin and Cisplatin to Osteosarcoma.
AB - [This corrects the article DOI: 10.1002/advs.201700821.].
PMID- 29938195
TI - Novel Therapeutic Targets in Axial Spondyloarthritis.
AB - Purpose of review: Axial spondyloarthritis remains an area of significant unmet
clinical need with only two immune pathways currently targeted by licenced
therapies compared to other immune-mediated inflammatory joint disorders such as
rheumatoid arthritis where a multitude of therapeutic options are available. This
review will look at emerging therapeutic targets in axial spondyloarthritis
beyond the neutralisation of IL-17A and TNF by monoclonal antibodies. Recent
findings: Several promising targets are in various stages of pre-clinical and
clinical development in axial spondyloarthritis. These include small molecule
approaches to target transcription factors, epigenetic modification and
intracellular modulation of cytokine signalling by kinase inhibition. GM-CSF has
also emerged as a potential driver of inflammation. Summary: A number of novel
and promising therapeutic options are in various stages of development in axial
spondyloarthritis. The Janus kinase inhibitors have shown great promise in other
immune-mediated inflammatory disorders and will be an exciting addition to the
axial spondyloarthritis field as the first oral disease-modifying agents. GM-CSF
blockade also shows great promise since antibodies for neutralising this cytokine
are safe in patients and have shown efficacy in other immune-mediated
inflammatory diseases.
PMID- 29938197
TI - Non-monetary valuation using Multi-Criteria Decision Analysis: Sensitivity of
additive aggregation methods to scaling and compensation assumptions.
AB - Analytical methods for Multi-Criteria Decision Analysis (MCDA) support the non
monetary valuation of ecosystem services for environmental decision making. Many
published case studies transform ecosystem service outcomes into a common metric
and aggregate the outcomes to set land use planning and environmental management
priorities. Analysts and their stakeholder constituents should be cautioned that
results may be sensitive to the methods that are chosen to perform the analysis.
In this article, we investigate four common additive aggregation methods: global
and local multi-attribute scaling, the analytic hierarchy process, and compromise
programming. Using a hypothetical example, we explain scaling and compensation
assumptions that distinguish the methods. We perform a case study application of
the four methods to re-analyze a data set that was recently published in
Ecosystem Services and demonstrate how results are sensitive to the methods.
PMID- 29938196
TI - Synthesis, Radiolabelling and In Vitro Imaging of Multifunctional Nanoceramics.
AB - Molecular imaging has become a powerful technique in preclinical and clinical
research aiming towards the diagnosis of many diseases. In this work, we address
the synthetic challenges in achieving lab-scale, batch-to-batch reproducible
copper-64- and gallium-68-radiolabelled metal nanoparticles (MNPs) for cellular
imaging purposes. Composite NPs incorporating magnetic iron oxide cores with
luminescent quantum dots were simultaneously encapsulated within a thin silica
shell, yielding water-dispersible, biocompatible and luminescent NPs. Scalable
surface modification protocols to attach the radioisotopes 64Cu (t1/2=12.7 h) and
68Ga (t1/2=68 min) in high yields are reported, and are compatible with the time
frame of radiolabelling. Confocal and fluorescence lifetime imaging studies
confirm the uptake of the encapsulated imaging agents and their cytoplasmic
localisation in prostate cancer (PC-3) cells. Cellular viability assays show that
the biocompatibility of the system is improved when the fluorophores are
encapsulated within a silica shell. The functional and biocompatible SiO2 matrix
represents an ideal platform for the incorporation of 64Cu and 68Ga radioisotopes
with high radiolabelling incorporation.
PMID- 29938198
TI - Evidence of No Association Between Human Papillomavirus and Breast Cancer.
AB - Background: Globally, breast cancer is the most frequent cancer among women.
Studies reported an increased risk of breast cancer among women with prior
cervical dysplasia. This study aimed to describe the prevalence of human
papillomavirus (HPV) in breast cancer and explore if women with prior cervical
neoplasia carry an increased risk of HPV-positive breast cancer compared to women
without. Methods: This case-control study identified 193 Danish women diagnosed
with breast cancer (1998-2012) at Aarhus University Hospital or Copenhagen
University Hospital Herlev. Cases were 93 women with cervical intraepithelial
neoplasia grade 3 or worse (CIN3+) prior to breast cancer. Controls were 100
women without prior cervical dysplasia. HPV testing and genotyping were done
using SPF10 PCR-DEIA-LiPA25 and an in-house semi-Q-PCR assay. Results: Overall
HPV prevalence in breast cancer for the assays was 1.55% (95% CI 0.32-4.48) and
0.52% (95% CI 0.01-2.85). There was no difference in HPV prevalence between cases
and controls (2.15 vs. 1.00%, p = 0.61 and 1.08 vs. 0.00%, p = 0.48). HPV
prevalence in CIN3+ was 94.62% (95% CI 0.88-0.98). Concordance between the assays
was 98.60%. Conclusion: HPV prevalence in breast cancer is very low suggesting no
etiological correlation between HPV and breast cancer.
PMID- 29938199
TI - Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel-Lindau-Deficient
Renal Cancer.
AB - The most common type of the renal cancers detected in humans is clear cell renal
cell carcinomas (ccRCCs). These tumors are usually initiated by biallelic gene
inactivation of the Von Hippel-Lindau (VHL) factor in the renal epithelium, which
deregulates the hypoxia-inducible factors (HIFs) HIF1alpha and HIF2alpha, and
provokes their constitutive activation irrespective of the cellular oxygen
availability. While HIF1alpha can act as a ccRCC tumor suppressor, HIF2alpha has
emerged as the key HIF isoform that is essential for ccRCC tumor progression.
Indeed, preclinical and clinical data have shown that pharmacological inhibitors
of HIF2alpha can efficiently combat ccRCC growth. In this review, we discuss the
molecular basis underlying the oncogenic potential of HIF2alpha in ccRCC by
focusing on those pathways primarily controlled by HIF2alpha that are thought to
influence the progression of these tumors.
PMID- 29938200
TI - Use of Haploid Model of Candida albicans to Uncover Mechanism of Action of a
Novel Antifungal Agent.
AB - Antifungal agents for the treatment of Candida albicans infections are limited.
We recently discovered a novel antifungal small molecule, SM21, with promising in
vivo activity. Herein, we employed the newly developed C. albicans haploid
toolbox to uncover the mechanism of action of SM21. Comprehensive RNA-Seq
analyses of the haploid susceptible GZY803 strain revealed significant gene
expression changes related to mitochondria when exposed to SM21. Mitochondrial
structure visualization and measurement of ATP generation, reactive oxygen
species (ROS) levels, and the antioxidant potential of SM21-treated and untreated
GZY803, mitochondrial structure defective haploid mutant (dnm1Delta), and wild
type diploid SC5314 strains confirmed defects in mitochondria. Exploiting the
advantage of C. albicans haploids as a single ploidy model, we further exposed
GZY803 to repetitive treatments of SM21 in order to generate resistant mutants.
Three colonies designated S3, S5 and S6, which displayed resistance to SM21, were
isolated. All resistant strains exhibited enhanced transcriptomic responses for
peptide and protein metabolism and secreted aspartate proteases (SAPs) activity
under SM21 treatment compared to the parent strain GZY803. Consistently,
supplementing the resistant strains, GZY803, and SC5314 with peptone, a form of
digested peptides, decreased susceptibility to SM21. The present study
demonstrates the usefulness of haploid C. albicans model in antifungal drug
discovery. The findings will be invaluable to develop SM21 as a novel antifungal
agent, which will benefit millions of patients suffering from Candida infections.
PMID- 29938202
TI - Lipid A Has Significance for Optimal Growth of Coxiella burnetii in Macrophage
Like THP-1 Cells and to a Lesser Extent in Axenic Media and Non-phagocytic Cells.
AB - Lipid A is an essential basal component of lipopolysaccharide of most Gram
negative bacteria. Inhibitors targeting LpxC, a conserved enzyme in lipid A
biosynthesis, are antibiotic candidates against Gram-negative pathogens. Here we
report the characterization of the role of lipid A in Coxiella burnetii growth in
axenic media, monkey kidney cells (BGMK and Vero), and macrophage-like THP-1
cells by using a potent LpxC inhibitor -LPC-011. We first determined the
susceptibility of C. burnetii LpxC to LPC-011 in a surrogate E. coli model. In E.
coli, the minimum inhibitory concentration (MIC) of LPC-011 against C. burnetii
LpxC is < 0.05 MUg/mL, a value lower than the inhibitor's MIC against E. coli
LpxC. Considering the inhibitor's problematic pharmacokinetic properties in vivo
and Coxiella's culturing time up to 7 days, the stability of LPC-011 in cell
cultures was assessed. We found that regularly changing inhibitor-containing
media was required for sustained inhibition of C. burnetii LpxC in cells. Under
inhibitor treatment, Coxiella has reduced growth yields in axenic media and
during replication in non-phagocytic cells, and has a reduced number of
productive vacuoles in such cells. Inhibiting lipid A biosynthesis in C. burnetii
by the inhibitor was shown in a phase II strain transformed with chlamydial kdtA.
This exogenous KdtA enzyme modifies Coxiella lipid A with an alpha-Kdo-(2 -> 8)
alpha-Kdo epitope that can be detected by anti-chlamydia genus antibodies. In
inhibitor-treated THP-1 cells, Coxiella shows severe growth defects characterized
by poor vacuole formation and low growth yields. Coxiella progenies prepared from
inhibitor-treated cells retain the capability of normally infecting all tested
cells in the absence of the inhibitor, which suggests a dispensable role of lipid
A for infection and early vacuole development. In conclusion, our data suggest
that lipid A has significance for optimal development of Coxiella-containing
vacuoles, and for robust multiplication of C. burnetii in macrophage-like THP-1
cells. Unlike many bacteria, C. burnetii replication in axenic media and non
phagocytic cells was less dependent on normal lipid A biosynthesis.
PMID- 29938203
TI - Impact of Glutathione on Wines Oxidative Stability: A Combined Sensory and
Metabolomic Study.
AB - This paper is a comprehensive study regarding the role of glutathione as a
natural antioxidant on white wines aging potential. It includes sensory and
ultrahigh resolution mass spectrometry (FTICR-MS) metabolomics of aged chardonnay
wines from 2008 to 2009 vintages, made after glutathione spiking at alcoholic
fermentation or bottling. The closure effect was also considered. The sensory
analysis revealed a clear vintage, closure and glutathione effect on wines
oxidative character after several years of bottle aging. Spearman rank
correlation was applied to link the sensory analysis and the exact mass
information from FT-ICR-MS. FTICR-MS along with multivariate statistical analyses
put in evidence that glutathione efficiency against wines sensory oxidative
stability is related to wines antioxidant metabolome consisting of N- and S-
containing compounds like amino acids, aromatic compounds and peptides. The
chemical composition and origin of wines antioxidant metabolome suggests that its
management since the very beginning of the vinification process is a key factor
to estimate wines aging potential.
PMID- 29938205
TI - Age at First Sexual Intercourse and Multiple Sexual Partnerships Among Women in
Nigeria: A Cross-Sectional Analysis.
AB - Background: Little is known about sexual behavior such as first sexual
intercourse and number of sexual partnerships among women in Nigeria. Early
sexual debut is a widely recognized public health issue due to its influence on
higher lifetime sexual partners which in turn is associated with increased
vulnerability to pregnancy complications, HIV/AIDS and other and sexually
transmitted diseases. In the present study, we attempted to explore the patterns
of age of sexual debut and multiple sexual partnerships among women of
reproductive age in Nigeria. Methods: Women who responded to the questions about
the age at first sex and number of lifetime sex partners were selected from two
latest rounds Nigeria Demographic and Health Survey (DHS). In total 60,611 women
aged between 15 and 49 years were selected for this analysis. Age at sexual debut
was used as the predictor of multiple sexual partnerships which was assessed by
multinomial regression models with logit link function in complex sample analysis
mode. Results: The median age at first sex was 16 years (Interquartile range 16
24). Age at first sexual intercourse below the age of 19 years was reported by
30.8% of the women. Respectively 45.4% (95%CI = 42.9-47.9) 49.8% (95%CI = 47.8
51.7) of the women reported experiencing first intercourse before reaching 15 and
17 years, whereas 46.9% (95%CI = 45.2-48.7) of the women reported being
monogamous and 47.2% (95%CI = 45.6-48.8) and 47.6% (95%CI = 43.8-51.3) had 2-3
and >3 lifetime sexual partners. In multivariable analysis after adjusting for
confounding factors, women having sexual debut below 18 years were found to be
significantly more likely to have 2-3 and more than 3 lifetime sexual partner.
Conclusion: The study concludes that an increasing proportion of Nigerian women
are experiencing sexual debut before reaching 15 years. The findings suggest that
early sexual debut is associated with multiple sexual partnerships which may
increase the risk of STIs. Stakeholders in health care system need to be aware
that early sexual debut can be associated with successive unsafe sexual practices
which can lead to adverse health outcomes including HIV infection and STIs, early
marriage, unwanted pregnancy, and abortion. Therefore, it is important to design
effective interventions to encourage women delay sexual debut to help prevent
unintended pregnancies and decrease the disproportionate burden of adverse health
outcomes.
PMID- 29938206
TI - Comparing the Performance of Bread and Breakfast Cereals, Dairy, and Meat in
Nutritionally Balanced and Sustainable Diets.
AB - Objective: To quantify the performance of food products in a sustainable diet
based on the balance of their contribution to nutrient intake and environmental
impact, within the context of the Dutch diet. Design: While fixing the quantity
of a specific food group at different levels, optimized diets that met nutrient
requirements and stayed as close as possible to the current Dutch diet were
calculated, in order to understand its potential environmental impact and its
nutritional quality. Bread & breakfast cereals, dairy, and meat were compared
between 0 and 250% of current intake. Their performance is expressed in the
relationship between the quantity of these food products and (1) the
environmental impact of diets and (2) the nutrient balance of the diets. Setting:
The Netherlands. Subjects: Women aged 31-50. Results: The amount of bread &
breakfast cereals in the optimized diets were inversely correlated with their
environmental impact. The nutrient balance of the optimized diets was maintained
despite varying cereal content, with the expected improvement over the current
diet. Increasing amounts of dairy in the optimized diet were associated with an
increase in environmental impact and meat with a steep increase. The nutrient
balance of optimized diets with varying dairy and meat contents was also
maintained at high levels, even at 0% content. Conclusions: Bread and breakfast
cereals are sources of nutrients with a better environmental performance compared
to dairy or meat within the context of the Dutch diet. It is possible to optimize
diets for environmental impact whilst maintaining a high nutrient balance.
PMID- 29938204
TI - The Induction of Bone Formation: The Translation Enigma.
AB - A paradigmatic shift in the way of thinking is what bone tissue engineering
science requires to decrypt the translation conundrum from animal models into
human. The deductive work of Urist (1965), who discerned the principle of bone
induction from the pioneering works of Senn, Huggins, Lacroix, Levander, and
other bone regenerative scientists, provided the basis that has assisted future
bone tissue regenerative scientists to extend the bone tissue engineering field
and its potential uses for bone regenerative medicine in humans. However, major
challenges remain that are preventing the formation of bone by induction
clinically. Growing experimental evidence is indicating that bone inductive
studies are non-translatable from animal models into a clinical environment. This
is preventing bone tissue engineering from reaching the next phase in
development. Countless studies are trying to discern how the formation of bone by
induction functions mechanistically, so as to try and solve this enigmatic
problem. However, are the correct questions being asked? Why do bone inductive
animal studies not translate into humans? Why do bone induction principles not
yield the same extent of bone formation as an autogenous bone graft? What are
bone tissue engineering scientists missing? By critically re-assessing the past
and present discoveries of the bone induction field, this review article attempts
to re-discover the field of bone formation by induction, identifying some key
features that may have been missed. These include a detailed library of all
proteins in bones and their arrangement in the 3D superstructure of the bone
together with some other important criteria not considered by tissue engineering
scientists. The review therefore not only re-iterates possible avenues of
research that need to be re-explored but also seeks to guide present and future
scientists in how they assess their own research in light of experimental design
and results. By addressing these issues bone formation by induction without
autografts might finally become clinically viable.
PMID- 29938201
TI - Staphylococcus aureus CC30 Lineage and Absence of sed,j,r-Harboring Plasmid
Predict Embolism in Infective Endocarditis.
AB - Staphylococcus aureus induces severe infective endocarditis (IE) where embolic
complications are a major cause of death. Risk factors for embolism have been
reported such as a younger age or larger IE vegetations, while methicillin
resistance conferred by the mecA gene appeared as a protective factor. It is
unclear, however, whether embolism is influenced by other S. aureus
characteristics such as clonal complex (CC) or virulence pattern. We examined
clinical and microbiological predictors of embolism in a prospective multicentric
cohort of 98 French patients with monomicrobial S. aureus IE. The genomic
contents of causative isolates were characterized using DNA array. To preserve
statistical power, genotypic predictors were restricted to CC, secreted virulence
factors and virulence regulators. Multivariate regularized logistic regression
identified three independent predictors of embolism. Patients at higher risk were
younger than the cohort median age of 62.5 y (adjusted odds ratio [OR] 0.14; 95%
confidence interval [CI] 0.05-0.36). S. aureus characteristics predicting
embolism were a CC30 genetic background (adjusted OR 9.734; 95% CI 1.53-192.8)
and the absence of pIB485-like plasmid-borne enterotoxin-encoding genes sed, sej,
and ser (sedjr; adjusted OR 0.07; 95% CI 0.004-0.457). CC30 S. aureus has been
repeatedly reported to exhibit enhanced fitness in bloodstream infections, which
might impact its ability to cause embolism. sedjr-encoded enterotoxins, whose
superantigenic activity is unlikely to protect against embolism, possibly acted
as a proxy to others genes of the pIB485-like plasmid found in genetically
unrelated isolates from mostly embolism-free patients. mecA did not independently
predict embolism but was strongly associated with sedjr. This mecA-sedjr
association might have driven previous reports of a negative association of mecA
and embolism. Collectively, our results suggest that the influence of S. aureus
genotypic features on the risk of embolism may be stronger than previously
suspected and independent of clinical risk factors.
PMID- 29938207
TI - HMGA1a Induces Alternative Splicing of the Estrogen Receptor-alphalpha Gene by
Trapping U1 snRNP to an Upstream Pseudo-5' Splice Site.
AB - Objectives: The high-mobility group A protein 1a (HMGA1a) protein is known as a
transcription factor that binds to DNA, but recent studies have shown it exerts
novel functions through RNA-binding. We were prompted to decipher the mechanism
of HMGA1a-induced alternative splicing of the estrogen receptor alpha (ERalpha)
that we recently reported would alter tamoxifen sensitivity in MCF-7 TAMR1 cells.
Methods: Endogenous expression of full length ERalpha66 and its isoform ERalpha46
were evaluated in MCF-7 breast cancer cells by transient expression of HMGA1a and
an RNA decoy (2'-O-methylated RNA of the HMGA1a RNA-binding site) that binds to
HMGA1a. RNA-binding of HMGA1a was checked by RNA-EMSA. In vitro splicing assay
was performed to check the direct involvement of HMGA1a in splicing regulation.
RNA-EMSA assay in the presence of purified U1 snRNP was performed with psoralen
UV crosslinking to check complex formation of HMGA1a-U1 snRNP at the upstream
pseudo-5' splice site of exon 1. Results: HMGA1a induced exon skipping of a
shortened exon 1 of ERalpha in in vitro splicing assays that was blocked by the
HMGA1a RNA decoy and sequence-specific RNA-binding was confirmed by RNA-EMSA. RNA
EMSA combined with psoralen UV crosslinking showed that HMGA1a trapped purified
U1 snRNP at the upstream pseudo-5' splice site. Conclusions: Regulation of
ERalpha alternative splicing by an HMGA1a-trapped U1 snRNP complex at the
upstream 5' splice site of exon 1 offers novel insight on 5' splice site
regulation by U1 snRNP as well as a promising target in breast cancer therapy
where alternative splicing of ERalpha is involved.
PMID- 29938208
TI - Pulmonary Artery Size in Interstitial Lung Disease and Pulmonary Hypertension:
Association with Interstitial Lung Disease Severity and Diagnostic Utility.
AB - Purpose: It is postulated that ILD causes PA dilatation independent of the
presence of pulmonary hypertension (PH), so the use of PA size to screen for PH
is not recommended. The aims of this study were to investigate the association of
PA size with the presence and severity of ILD and to assess the diagnostic
accuracy of PA size for detecting PH. Methods: Incident patients referred to a
tertiary PH centre underwent baseline thoracic CT, MRI and right heart
catheterisation (RHC). Pulmonary artery diameter was measured on CT pulmonary
angiography and pulmonary arterial areas on MRI. A thoracic radiologist scored
the severity of ILD on CT from 0 to 4, 0 = absent, 1 = 1-25%, 2 = 26-50%, 3 = 51
75%, and 4 = 76-100% extent of involvement. Receiver operating characteristic
analysis and linear regression were employed to assess diagnostic accuracy and
independent associations of PA size. Results: 110 had suspected PH due to ILD
(age 65 years (SD 13), M:F 37:73) and 379 had suspected PH without ILD (age 64
years (SD 13), M:F 161:218). CT derived main PA diameter was accurate for
detection of PH in patients both with and without ILD - AUC 0.873, p =< 0.001,
and AUC 0.835, p =< 0.001, respectively, as was MRI diastolic PA area, AUC 0.897,
p =< 0.001, and AUC 0.857, p =< 0.001, respectively Significant correlations were
identified between mean pulmonary arterial pressure (mPAP) and PA diameter in ILD
(r = 0.608, p < 0.001), and non-ILD cohort (r = 0.426, p < 0.001). PA size was
independently associated with mPAP (p < 0.001) and BSA (p = 0.001), but not with
forced vital capacity % predicted (p = 0.597), Transfer factor of the lungs for
carbon monoxide (TLCO) % predicted (p = 0.321) or the presence of ILD on CT (p =
0.905). The severity of ILD was not associated with pulmonary artery dilatation
(r = 0.071, p = 0.459). Conclusions: Pulmonary arterial pressure elevation leads
to pulmonary arterial dilation, which is not independently influenced by the
presence or severity of ILD measured by FVC, TLCO, or disease severity on CT.
Pulmonary arterial diameter has diagnostic value in patients with or without ILD
and suspected PH.
PMID- 29938209
TI - Impacts and Uncertainties of +2 degrees C of Climate Change and Soil Degradation
on European Crop Calorie Supply.
AB - Even if global warming is kept below +2 degrees C, European agriculture will be
significantly impacted. Soil degradation may amplify these impacts substantially
and thus hamper crop production further. We quantify biophysical consequences and
bracket uncertainty of +2 degrees C warming on calories supply from 10 major
crops and vulnerability to soil degradation in Europe using crop modeling. The
Environmental Policy Integrated Climate (EPIC) model together with regional
climate projections from the European branch of the Coordinated Regional
Downscaling Experiment (EURO-CORDEX) was used for this purpose. A robustly
positive calorie yield change was estimated for the EU Member States except for
some regions in Southern and South-Eastern Europe. The mean impacts range from
+30 Gcal ha-1 in the north, through +25 and +20 Gcal ha-1 in Western and Eastern
Europe, respectively, to +10 Gcal ha-1 in the south if soil degradation and heat
impacts are not accounted for. Elevated CO2 and increased temperature are the
dominant drivers of the simulated yield changes in high-input agricultural
systems. The growth stimulus due to elevated CO2 may offset potentially negative
yield impacts of temperature increase by +2 degrees C in most of Europe. Soil
degradation causes a calorie vulnerability ranging from 0 to 50 Gcal ha-1 due to
insufficient compensation for nutrient depletion and this might undermine climate
benefits in many regions, if not prevented by adaptation measures, especially in
Eastern and North-Eastern Europe. Uncertainties due to future potentials for crop
intensification are about 2-50 times higher than climate change impacts.
PMID- 29938210
TI - Biogeophysical Impacts of Land-Use Change on Climate Extremes in Low-Emission
Scenarios: Results From HAPPI-Land.
AB - The impacts of land use have been shown to have considerable influence on
regional climate. With the recent international commitment to limit global
warming to well below 2 degrees C, emission reductions need to be ambitious and
could involve major land-use change (LUC). Land-based mitigation efforts to curb
emissions growth include increasing terrestrial carbon sequestration through
reforestation, or the adoption of bioenergy crops. These activities influence
local climate through biogeophysical feedbacks, however, it is uncertain how
important they are for a 1.5 degrees climate target. This was the motivation for
HAPPI-Land: the half a degree additional warming, prognosis, and projected
impacts-land-use scenario experiment. Using four Earth system models, we present
the first multimodel results from HAPPI-Land and demonstrate the critical role of
land use for understanding the characteristics of regional climate extremes in
low-emission scenarios. In particular, our results show that changes in
temperature extremes due to LUC are comparable in magnitude to changes arising
from half a degree of global warming. We also demonstrate that LUC contributes to
more than 20% of the change in temperature extremes for large land areas
concentrated over the Northern Hemisphere. However, we also identify sources of
uncertainty that influence the multimodel consensus of our results including how
LUC is implemented and the corresponding biogeophysical feedbacks that perturb
climate. Therefore, our results highlight the urgent need to resolve the
challenges in implementing LUC across models to quantify the impacts and consider
how LUC contributes to regional changes in extremes associated with sustainable
development pathways.
PMID- 29938211
TI - Trial of infographics in Northern Ireland (TINI): Preliminary evaluation and
results of a randomized controlled trial comparing infographics with text.
AB - : Infographics represent a potential means of improving public knowledge about
cancer. However, there is little experimental evidence of their efficacy. This
preliminary study investigates whether infographics are superior to text for the
communication of information about cancer risk in old age via a three armed
randomized controlled trial. Trial involved allocation concealment and block
randomization of 30 male participants aged over 50 to receive text information
(control) or one of two infographics (interventions). Participants who viewed an
infographic were more likely to know the correct association between cancer risk
and old age compared with those viewing text information (risk ratio = 3.0, 95%
confidence interval 0.82-10.90). Participants had limited understanding of the
phrases "cancer incidence" and "cancer prevalence" but good understanding of the
phrases "cancer risk factor" and "cancer stage." Possession of good numerical
skills appears to be a key determinant of ability to extract meaning from
statistical information provided; regardless of format. Initial results suggest
icon array infographics may be more effective communication mediums than text but
further study with more participants and an updated infographic is necessary to
confirm this finding. TRIAL REGISTRATION NUMBER: ISRCTN33951209.
PMID- 29938212
TI - Patient Portal Usage in Pediatric Urology: Is it Meaningful Use for Everyone?
AB - Introduction: The Affordable Care Act promotes multiple directives for meaningful
use of the Electronic Health Record, such as patient/provider portals, to
increase patient engagement. Although portal use is common within adult
healthcare, little information exists regarding pediatric portal use. We examined
pediatric urology patient portal enrollment and activation patterns at a tertiary
pediatric hospital in Southern California by race/ethnicity, preferred language,
gender, and residential region. Methods: Retrospective Electronic Health Record
analysis of enrollment in patient portal from January 2010 to May 2016 among
10,464 patients with at least one outpatient urology clinic visit. Differences in
adoption rates were examined using logistic regression for the following
categories: activated (or caregiver activated); code accepted not activated;
declined; or activated/then deactivated. Results: Overall, 46.5% of
patients/caregivers activated the portal. Primarily Spanish-speaking patients
were less likely to activate (OR 0.25, p <.001) than English-speaking patients.
Males (OR 0.89, p =.004); those self-identifying racially as Other (not White,
Asian, or African American) (OR 0.47, p <.001); and Hispanic patients (OR 0.49, p
<.001) were less likely to activate. Suburban patients were up to 3 times more
likely to activate portals than central urban patients depending on the region
(OR 2.94, p <.001). Multivariate logistic regression demonstrated Spanish
speaking patients were 3 times less likely to activate while controlling for
demographic and region variables. Conclusions: Primary language and socioeconomic
factors may be significant barriers to portal adoption. Patient education to
reduce these barriers may increase portal acceptance and increase meaningfulness
to the portal for patients/parents and providers.
PMID- 29938213
TI - Validation and Reliability of the 12-item Zarit Burden Interview among Informal
Caregivers of Elderly Persons in Nigeria.
AB - Research on ageing in Nigeria has shown that informal care places economic and
psychological strain on the caregivers of the elderly persons. However, objective
method of assessment of the burden of care for the elderly among caregivers is
lacking. This study was aimed at validating the 12-item Zarit Burden Interview
(ZBI) among caregivers of elderly persons in Nigeria in correlation with the Katz
Index of Independence in Activities of Daily Living (Katz-ADL), the General
Health Questionnaire (GHQ-12) and the Modified Conflicts Tactics Scale for Elder
Abuse (MCTS). Eighty primary caregivers of community-dwelling elders were
selected using a two-stage cluster sampling from two communities. Principal
component analysis with varimax rotation was used to determine the factor
structure of the ZBI. Construct validity was assessed using Spearman's
correlations between the ZBI, the GHQ-12, Katz ADL and MCTS. Internal consistency
and instrument reliability were examined with the Cronbach's alpha split-half
correlation. Three factors with eigenvalues greater than 1.0 were extracted on
the exploratory factor analysis comprising all 12 items accounting for 68.0% of
the total item variance. The reliability analysis gave a Cronbach's alpha of 0.90
and a split-half correlation coefficient of 0.84. Spearman's correlation (rs)
showed good correlation between the ZBI scores and GHQ-12 (rs=0.44, p<0.001),
MCTS (rs=0.43, p<0.001) and Katz ADL (rs= -0.50, p <0.001). The 12-item ZBI is a
valid and reliable tool for assessing burden in informal settings among
caregivers of elderly persons. The tool can be used to assess burden of care
among caregivers of elderly persons in community settings.
PMID- 29938214
TI - Neural Correlates of Odor Learning in the Presynaptic Microglomerular Circuitry
in the Honeybee Mushroom Body Calyx.
AB - The mushroom body (MB) in insects is known as a major center for associative
learning and memory, although exact locations for the correlating memory traces
remain to be elucidated. Here, we asked whether presynaptic boutons of olfactory
projection neurons (PNs) in the main input site of the MB undergo neuronal
plasticity during classical odor-reward conditioning and correlate with the
conditioned behavior. We simultaneously measured Ca2+ responses in the boutons
and conditioned behavioral responses to learned odors in honeybees. We found that
the absolute amount of the neural change for the rewarded but not for the
unrewarded odor was correlated with the behavioral learning rate across
individuals. The temporal profile of the induced changes matched with odor
response dynamics of the MB-associated inhibitory neurons, suggestive of activity
modulation of boutons by this neural class. We hypothesize the circuit-specific
neural plasticity relates to the learned value of the stimulus and underlies the
conditioned behavior of the bees.
PMID- 29938215
TI - Locomotor- and Reward-Enhancing Effects of Cocaine Are Differentially Regulated
by Chemogenetic Stimulation of Gi-Signaling in Dopaminergic Neurons.
AB - Dopamine plays a key role in the cellular and behavioral responses to drugs of
abuse, but the implication of metabotropic regulatory input to dopaminergic
neurons on acute drug effects and subsequent drug-related behavior remains
unclear. Here, we used chemogenetics [Designer Receptors Exclusively Activated by
Designer Drugs (DREADDs)] to modulate dopamine signaling and activity before
cocaine administration in mice. We show that chemogenetic inhibition of
dopaminergic ventral tegmental area (VTA) neurons differentially affects
locomotor and reward-related behavioral responses to cocaine. Stimulation of Gi
coupled DREADD (hM4Di) expressed in dopaminergic VTA neurons persistently reduced
the locomotor response to repeated cocaine injections. An attenuated locomotor
response was seen even when a dual-viral vector approach was used to restrict
hM4Di expression to dopaminergic VTA neurons projecting to the nucleus accumbens.
Surprisingly, despite the attenuated locomotor response, hM4Di-mediated
inhibition of dopaminergic VTA neurons did not prevent cocaine sensitization, and
the inhibitory effect of hM4Di-mediated inhibition was eliminated after
withdrawal. In the conditioned place-preference paradigm, hM4Di-mediated
inhibition did not affect cocaine-induced place preference; however, the
extinction period was extended. Also, hM4Di-mediated inhibition had no effect on
preference for a sugar-based reward over water but impaired motivation to work
for the same reward in a touchscreen-based motivational assay. In addition, to
support that VTA dopaminergic neurons operate as regulators of reward motivation
toward both sugar and cocaine, our data suggest that repeated cocaine exposure
leads to adaptations in the VTA that surmount the ability of Gi-signaling to
suppress and regulate VTA dopaminergic neuronal activity.
PMID- 29938216
TI - dSTIM- and Ral/Exocyst-Mediated Synaptic Release from Pupal Dopaminergic Neurons
Sustains Drosophila Flight.
AB - Manifestation of appropriate behavior in adult animals requires developmental
mechanisms that help in the formation of correctly wired neural circuits. Flight
circuit development in Drosophila requires store-operated calcium entry (SOCE)
through the STIM/Orai pathway. SOCE-associated flight deficits in adult
Drosophila derive extensively from regulation of gene expression in pupal
neurons, and one such SOCE-regulated gene encodes the small GTPase Ral. The
cellular mechanism by which Ral helps in maturation of the flight circuit was not
understood. Here, we show that knockdown of components of a Ral effector, the
exocyst complex, in pupal neurons also leads to reduced flight bout durations,
and this phenotype derives primarily from dopaminergic neurons. Importantly,
synaptic release from pupal dopaminergic neurons is abrogated upon knockdown of
dSTIM, Ral, or exocyst components. Ral overexpression restores the diminished
synaptic release of dStim knockdown neurons as well as flight deficits associated
with dSTIM knockdown in dopaminergic neurons. These results identify Ral-mediated
vesicular release as an effector mechanism of neuronal SOCE in pupal dopaminergic
neurons with functional consequences on flight behavior.
PMID- 29938217
TI - Extensive marine anoxia during the terminal Ediacaran Period.
AB - The terminal Ediacaran Period witnessed the decline of the Ediacara biota (which
may have included many stem-group animals). To test whether oceanic anoxia might
have played a role in this evolutionary event, we measured U isotope compositions
(delta238U) in sedimentary carbonates from the Dengying Formation of South China
to obtain new constraints on the extent of global redox change during the
terminal Ediacaran. We found the most negative carbonate delta238U values yet
reported (-0.95 per mil), which were reproduced in two widely spaced coeval
sections spanning the terminal Ediacaran Period (551 to 541 million years ago).
Mass balance modeling indicates an episode of extensive oceanic anoxia, during
which anoxia covered >21% of the seafloor and most U entering the oceans was
removed into sediments below anoxic waters. The results suggest that an expansion
of oceanic anoxia and temporal-spatial redox heterogeneity, independent of other
environmental and ecological factors, may have contributed to the decline of the
Ediacara biota and may have also stimulated animal motility.
PMID- 29938219
TI - Macroeconomic evidence suggests that asylum seekers are not a "burden" for
Western European countries.
AB - This paper aims to evaluate the economic and fiscal effects of inflows of asylum
seekers into Western Europe from 1985 to 2015. It relies on an empirical
methodology that is widely used to estimate the macroeconomic effects of
structural shocks and policies. It shows that inflows of asylum seekers do not
deteriorate host countries' economic performance or fiscal balance because the
increase in public spending induced by asylum seekers is more than compensated
for by an increase in tax revenues net of transfers. As asylum seekers become
permanent residents, their macroeconomic impacts become positive.
PMID- 29938218
TI - Immunity drives TET1 regulation in cancer through NF-kappaB.
AB - Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA
demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5
hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in
basal-like breast cancer (BLBC), genome-wide 5hmC changes related to TET1
regulation. We further demonstrate that TET1 repression is associated with high
expression of immune markers and high infiltration by immune cells. We identify
in BLBC tissues an anticorrelation between TET1 expression and the major
immunoregulator family nuclear factor kappaB (NF-kappaB). In vitro and in mice,
TET1 is down-regulated in breast cancer cells upon NF-kappaB activation through
binding of p65 to its consensus sequence in the TET1 promoter. We lastly show
that these findings extend to other cancer types, including melanoma, lung, and
thyroid cancers. Together, our data suggest a novel mode of regulation for TET1
in cancer and highlight a new paradigm in which the immune system can influence
cancer cell epigenetics.
PMID- 29938220
TI - Eavesdropping on the Arctic: Automated bioacoustics reveal dynamics in songbird
breeding phenology.
AB - Bioacoustic networks could vastly expand the coverage of wildlife monitoring to
complement satellite observations of climate and vegetation. This approach would
enable global-scale understanding of how climate change influences phenomena such
as migratory timing of avian species. The enormous data sets that autonomous
recorders typically generate demand automated analyses that remain largely
undeveloped. We devised automated signal processing and machine learning
approaches to estimate dates on which songbird communities arrived at arctic
breeding grounds. Acoustically estimated dates agreed well with those determined
via traditional surveys and were strongly related to the landscape's snow-free
dates. We found that environmental conditions heavily influenced daily variation
in songbird vocal activity, especially before egg laying. Our novel approaches
demonstrate that variation in avian migratory arrival can be detected
autonomously. Large-scale deployment of this innovation in wildlife monitoring
would enable the coverage necessary to assess and forecast changes in bird
migration in the face of climate change.
PMID- 29938221
TI - Age and performance at fledging are a cause and consequence of juvenile mortality
between life stages.
AB - Should they stay or should they leave? The age at which young transition between
life stages, such as living in a nest versus leaving it, differs among species
and the reasons why are unclear. We show that offspring of songbird species that
leave the nest at a younger age have less developed wings that cause poorer
flight performance and greater mortality after fledging. Experimentally delayed
fledging verified that older age and better developed wings provide benefits of
reduced juvenile mortality. Young are differentially constrained in the age that
they can stay in the nest and enjoy these fitness benefits because of differences
among species in opposing predation costs while in the nest. This tension between
mortality in versus outside of the nest influences offspring traits and
performance and creates an unrecognized conflict between parents and offspring
that determines the optimal age to fledge.
PMID- 29938223
TI - The Chinese import ban and its impact on global plastic waste trade.
AB - The rapid growth of the use and disposal of plastic materials has proved to be a
challenge for solid waste management systems with impacts on our environment and
ocean. While recycling and the circular economy have been touted as potential
solutions, upward of half of the plastic waste intended for recycling has been
exported to hundreds of countries around the world. China, which has imported a
cumulative 45% of plastic waste since 1992, recently implemented a new policy
banning the importation of most plastic waste, begging the question of where the
plastic waste will go now. We use commodity trade data for mass and value,
region, and income level to illustrate that higher-income countries in the
Organization for Economic Cooperation have been exporting plastic waste (70% in
2016) to lower-income countries in the East Asia and Pacific for decades. An
estimated 111 million metric tons of plastic waste will be displaced with the new
Chinese policy by 2030. As 89% of historical exports consist of polymer groups
often used in single-use plastic food packaging (polyethylene, polypropylene, and
polyethylene terephthalate), bold global ideas and actions for reducing
quantities of nonrecyclable materials, redesigning products, and funding domestic
plastic waste management are needed.
PMID- 29938222
TI - A transgenic mouse for imaging activity-dependent dynamics of endogenous Arc mRNA
in live neurons.
AB - Localized translation plays a crucial role in synaptic plasticity and memory
consolidation. However, it has not been possible to follow the dynamics of memory
associated mRNAs in living neurons in response to neuronal activity in real time.
We have generated a novel mouse model where the endogenous Arc/Arg3.1 gene is
tagged in its 3' untranslated region with stem-loops that bind a bacteriophage
PP7 coat protein (PCP), allowing visualization of individual mRNAs in real time.
The physiological response of the tagged gene to neuronal activity is identical
to endogenous Arc and reports the true dynamics of Arc mRNA from transcription to
degradation. The transcription dynamics of Arc in cultured hippocampal neurons
revealed two novel results: (i) A robust transcriptional burst with prolonged ON
state occurs after stimulation, and (ii) transcription cycles continue even after
initial stimulation is removed. The correlation of stimulation with Arc
transcription and mRNA transport in individual neurons revealed that stimulus
induced Ca2+ activity was necessary but not sufficient for triggering Arc
transcription and that blocking neuronal activity did not affect the dendritic
transport of newly synthesized Arc mRNAs. This mouse will provide an important
reagent to investigate how individual neurons transduce activity into
spatiotemporal regulation of gene expression at the synapse.
PMID- 29938224
TI - Heterogeneity of spontaneous DNA replication errors in single isogenic
Escherichia coli cells.
AB - Despite extensive knowledge of the molecular mechanisms that control mutagenesis,
it is not known how spontaneous mutations are produced in cells with fully
operative mutation-prevention systems. By using a mutation assay that allows
visualization of DNA replication errors and stress response transcriptional
reporters, we examined populations of isogenic Escherichia coli cells growing
under optimal conditions without exogenous stress. We found that spontaneous DNA
replication errors in proliferating cells arose more frequently in subpopulations
experiencing endogenous stresses, such as problems with proteostasis, genome
maintenance, and reactive oxidative species production. The presence of these
subpopulations of phenotypic mutators is not expected to affect the average
mutation frequency or to reduce the mean population fitness in a stable
environment. However, these subpopulations can contribute to overall population
adaptability in fluctuating environments by serving as a reservoir of increased
genetic variability.
PMID- 29938226
TI - Upper and lower plate controls on the great 2011 Tohoku-oki earthquake.
AB - The great 2011 Tohoku-oki earthquake [moment magnitude (Mw) 9.0)] is the best
documented megathrust earthquake in the world, but its causal mechanism is still
in controversy because of the poor state of knowledge on the nature of the
megathrust zone. We constrain the structure of the Tohoku forearc using seismic
tomography, residual topography, and gravity data, which reveal a close
relationship between structural heterogeneities in and around the megathrust zone
and rupture processes of the 2011 Tohoku-oki earthquake. Its mainshock nucleated
in an area with high seismic velocity, low seismic attenuation, and strong
seismic coupling, probably indicating a large asperity (or a cluster of
asperities) in the megathrust zone. Strong coseismic high-frequency radiations
also occurred in high-velocity patches, whereas large afterslips took plate in
low-velocity areas, differences that may reflect changes in fault friction and
lithological variations. These structural heterogeneities in and around the
Tohoku megathrust originate from both the overriding and subducting plates, which
controlled the nucleation and rupture processes of the 2011 Tohoku-oki
earthquake.
PMID- 29938227
TI - Pulse Oximetry Targets in Extremely Premature Infants and Associated Mortality:
One-Size May Not Fit All.
AB - Oxygen saturation targets in premature infants have been investigated in multiple
international randomized controlled trials. Some trials have shown increased
mortality with targeting lower (85% to 89%) compared to higher (91% to 95%)
oxygen saturation ranges, while others have not. We will review the mortality
outcomes of the largest multi-centered trials and a post hoc study that observed
increased mortality at lower target ranges among small for gestational age
infants. The planned Neonatal Oxygen Prospective Meta-analysis (NeOProM)
collaborative will hopefully provide further insight into patient-specific risks,
which include growth status.
PMID- 29938225
TI - The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves
survival of preclinical brain tumor models.
AB - Poor survival rates of patients with tumors arising from or disseminating into
the brain are attributed to an inability to excise all tumor tissue (if
operable), a lack of blood-brain barrier (BBB) penetration of
chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance.
Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA damage
response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing
radiation (IR). ATM genetic ablation or pharmacological inhibition results in
tumor cell hypersensitivity to IR. We report the primary pharmacology of the
clinical-grade, exquisitely potent (cell IC50, 0.78 nM), highly selective
[>10,000-fold over kinases within the same phosphatidylinositol 3-kinase-related
kinase (PIKK) family], orally bioavailable ATM inhibitor AZD1390 specifically
optimized for BBB penetration confirmed in cynomolgus monkey brain positron
emission tomography (PET) imaging of microdosed 11C-labeled AZD1390 (Kp,uu,
0.33). AZD1390 blocks ATM-dependent DDR pathway activity and combines with
radiation to induce G2 cell cycle phase accumulation, micronuclei, and apoptosis.
AZD1390 radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma
cells generally being more radiosensitized than wild type. In in vivo syngeneic
and patient-derived glioma as well as orthotopic lung-brain metastatic models,
AZD1390 dosed in combination with daily fractions of IR (whole-brain or
stereotactic radiotherapy) significantly induced tumor regressions and increased
animal survival compared to IR treatment alone. We established a pharmacokinetic
pharmacodynamic-efficacy relationship by correlating free brain concentrations,
tumor phospho-ATM/phospho-Rad50 inhibition, apoptotic biomarker (cleaved caspase
3) induction, tumor regression, and survival. On the basis of the data presented
here, AZD1390 is now in early clinical development for use as a radiosensitizer
in central nervous system malignancies.
PMID- 29938228
TI - A Rare Case Presentation: Intravesical Catheter Knotting.
AB - Urethral catheterization is a common invasive procedure applied for several
purposes on children. Voiding cystourethrogram (VCUG) is a diagnostic
fluoroscopic procedure, which is commonly used in assessing urinary tract
infections in children and which requires urethral catheterization. We report a
case of intravesical catheter knotting, which is a rare complication of VCUG.
PMID- 29938229
TI - Retrograde Endoscopic Management of Completely Transected Ureter Discovered
Postoperatively.
AB - Inadvertent injury of the ureter is a known risk of pelvic surgery. If the injury
is noticed intraoperatively, the treatment is relatively straightforward.
However, if the discovery of the injury is delayed, the treatment is more
difficult and less assured. We encountered a case of a completely transected
ureter that had occurred during laparoscopic sigmoid colectomy and was diagnosed
on the 8th postoperative day. The patient was treated with minimally invasive
retrograde endoscopic realignment with excellent results. Therefore, we decided
to report this case and perform a literature review on this subject.
PMID- 29938230
TI - Management of Suspected Bladder Injury and Capsular Perforation After Holmium
Laser Enucleation of the Prostate.
AB - Background: Holmium laser enucleation of the prostate (HoLEP) is an attractive
and well-studied alternative to transurethral resection of the prostate and open
prostatectomy for the treatment of benign prostatic hyperplasia. There remains an
established steep learning curve with relatively few complications described in
the literature. A unique risk of HoLEP is injury of the bladder during
morcellation of the adenoma and potential iatrogenic intraperitoneal bladder
rupture. We present a rare complication of HoLEP demonstrated by two patients in
which capsular perforation resulted in subsequent abdominal distention secondary
to a large amount of irrigation fluid that leaked into the extraperitoneal space.
Uniquely, these cases were managed differently, and serve as guidance to the
HoLEP practitioner in postoperative management. Case Presentations: The first
case involved a 74-year-old male who was found to have significant abdominal
distention at the end of the procedure. Given an acute change in stability and
concern for bladder injury during morcellation, a minilaparotomy was performed
only to reveal extraperitoneal extravasation without intraperitoneal bladder
injury or perforation. In the second case, a 78-year-old male undergoing HoLEP
had a similar presentation of significant abdominal distention at the conclusion
of morcellation. Given a low suspicion for any bladder injury, the patient was
managed conservatively with diuretics. He was subsequently discharged on
postoperative day 1. Conclusion: Capsular perforation is not a rare phenomenon
that occurs during HoLEP. Rarely, perforations can lead to extravasation of
irrigation fluid into the extraperitoneal space masquerading as a potential
bladder injury related to morcellation because of the associated abdominal
distention. This presentation can occur in large glands or early in a surgeon's
learning curve when operative times are longer. When there is clear evidence to
suggest there is no bladder injury, these cases can be managed conservatively and
avoid the morbidity of an abdominal exploration.
PMID- 29938231
TI - A Performing Arts Intervention Improves Cognitive Dysfunction in 50 Hospitalized
Older Adults.
AB - Background and Objectives: Arts in medicine programs have emerged as a patient
centered approach that aims to improve health-related quality of life for
patients in U.S. hospitals. Storytelling and poetry/monologue recitation are
forms of arts-based experiences designed to enhance healing and are delivered by
an artist-in-residence. We evaluated the effect of a storytelling/poetry
experience on delirium screening scores and patient satisfaction in hospitalized
older adults. Research Design and Methods: We conducted an observational pre-post
study with a control group in the Acute Care for the Elders (ACE) unit at an
academic medical center. A convenience sample of 50 participants was recruited to
participate and complete two questionnaires measuring pain, anxiety, general well
being, and distress at hospital admission and at hospital discharge.
Multivariable regression models were used to compare delirium screening score
(primary outcome) between the control and intervention groups and to adjust for
the differences in baseline characteristics between groups. Results: At baseline
participants in the intervention group were younger and had significantly lower
cognitive impairment compared with those in the control group. Participants
exposed to the storytelling/poetry intervention had a lower delirium screening
score at hospital discharge compared with those in the control group. The result
remained significant after adjusting for age, baseline cognitive impairment, and
general well-being. Participants in the intervention group reported a high level
of satisfaction with the interaction with the artist delivering the intervention.
Discussion and Implications: An artist in residence-delivered storytelling/poetry
experience was associated with a lower delirium score at discharge in this pilot
study. Further larger studies in diverse inpatient settings are needed to examine
whether storytelling/poetry interventions or other types of arts in medicine
programs can prevent or reduce delirium in hospitalized older adults.
PMID- 29938232
TI - A Comprehensive Analysis of Morbidity Life Expectancies Among Older Hispanic
Subgroups in the United States: Variation by Nativity and Country of Origin.
AB - Background and Objectives: Although a clear advantage in mortality has been
documented among older Hispanic subgroups, particularly the foreign-born,
research examining health selectivity in morbidity life expectancies among older
Hispanics are scarce. Differences in sociocultural characteristics among Hispanic
subgroups may influence racial/ethnic and nativity disparities in morbidity.
Research examining the heterogeneity among older Hispanic subgroups may further
our understanding of why some Hispanics are able to preserve good health in old
age, while others experience a health disadvantage. Thus, the primary goal of
this analysis is to examine racial/ethnic, nativity, and country of origin
differences in morbidity life expectancies among older adults in the United
States. Research Design and Methods: We used individual-level data (1999-2015)
from the National Health Interview Survey to estimate Sullivan-based life tables
of life expectancies with morbidity and without morbidity by gender for U.S.-born
Mexicans, foreign-born Mexicans, U.S.-born Puerto Ricans, island-born Puerto
Ricans, foreign-born Cubans, and whites in mid-life (age 50), and late-life (age
65). Results: Hispanics are heterogeneous in morbidity life expectancies. Among
females, U.S.-born Mexicans, foreign-born Mexicans, and island-born Puerto Ricans
spent more late-life years with morbidity than whites. For men, U.S.-born Puerto
Ricans were the only Hispanic subgroup disadvantaged in the number of years lived
with morbidity. Conversely, foreign-born Cubans exhibited the healthiest outcomes
of all groups, regardless of gender. Discussion and Implications: Reducing the
risk for late-life morbidity must be informed by a comprehensive understanding of
a wide range of factors that shape health among older adults. Research should
avoid pan-ethnic groupings that overlook important differences in chronic disease
risk profiles among Hispanic subgroups. Recognizing the various sociocultural and
environmental processes that underlie Hispanic subpopulations is important for
development and implementation of social and public health policies aimed at
ameliorating negative health outcomes of late-life morbidity among minority and
immigrant groups.
PMID- 29938233
TI - Impact of erythrocyte species on assays for influenza serology.
AB - The influenza viruses have the ability to agglutinate erythrocytes by binding to
sialic acid receptors on the host cell. Human influenza viruses preferentially
bind to sialic acid linked to galactose by alpha 2.6 linkage, while avian
influenza viruses preferentially bind to sialic acid linked to Gal by alpha 2.3
linkage. There is a close correlation between the ability of influenza A viruses
to agglutinate erythrocytes from different animal species and their receptor
specificity. The haemagglutination and haemagglutination inhibition assays are
influenced by the species of erythrocytes. To provide an overview of the
expression of sialic acid receptors on different erythrocytes, avian (turkey,
chicken, pigeon) and mammalian (sheep, horse, human) species have been analysed
by flow cytometry. Chicken, turkey and human erythrocytes display both types of
linkages. Horse and sheep erythrocytes show almost exclusively alpha 2.3 Gal
linkages, while pigeon erythrocytes express almost exclusively alpha 2.6 Gal
linkages. The erythrocytes from the same avian and mammalian species have been
evaluated by haemagglutination and haemagglutination inhibition assays with
seasonal and avian strains. Chicken and turkey erythrocytes seem to be the most
appropriate for both assays with seasonal influenza strains, in addition to
pigeon erythrocytes, particularly for the B strains. In the case of the avian
strain, chicken erythrocytes are suitable for haemagglutination assay and horse
erythrocytes for haemagglutination inhibition assay. The choice of erythrocytes
has a significant impact on the titres measured by both assays.
PMID- 29938234
TI - Measles outbreak from February to August 2017 in Messina, Italy.
AB - Introduction: Measles continues to be a major public health issue worldwide, with
high morbidity and mortality rates. The disease remains endemic in 14 European
countries, including Italy where, from 2013 to 2016, over 5,000 cases have been
reported. In 2017, many Italian regions, including Sicily, have reported many
cases of measles. In this study, we described the latest measles outbreak in the
city of Messina, from 1st February to 31st August 2017. Methods: We considered
all reported measles cases that came to the "Public Health, Epidemiology and
Preventive Medicine" Operative Unit of the Messina Provincial Health Agency
Prevention Department, which receives all reported cases of measles in the
Messina province. Results: From 1st February to 31st August 2017, a total of 59
measles cases were reported, of which 44 were confirmed, nine were classified as
possible, four were probable and two cases were discarded. Of the 57 possible,
probable and confirmed cases, 31 (54%) were males and 26 (46%) were females.
Moreover, 54 (95%) had not been previously vaccinated while the remaining cases
had documented evidence of one (two cases) or two doses (one case). Genotype B3
was identified in 39/44 cases (88,6%) by the regional reference laboratory in
Palermo. Conclusions: Despite the development of an effective vaccination,
unfortunately measles continues to threaten the lives of millions of children
worldwide each year. The suboptimal immunization level in Italy has led to an
increase in the transmission of measles with detrimental effects on both public
health and ongoing measles elimination efforts.
PMID- 29938235
TI - "PErCEIVE in Umbria": evaluation of anti-influenza vaccination's perception among
Umbrian pharmacists.
AB - Vaccines recommendations are available for both healthcare professionals and the
general public, but although the vaccination is the most effective method to
prevent infectious diseases, the coverage is still behind the recommended rate.
In Italy, according to a recent study, the anti-flu vaccination rate among
healthcare worker range between 9% to 30%. The aim of our study was to identify
knowledge, attitude and behaviours regarding influenza vaccination among
community pharmacists in order to increase the coverage rate among healthcare
professional. "PErCEIVE (Pharmacist Perception on Influenza Vaccine) in Umbria"
was a cross sectional survey among community pharmacists in Umbria conducted
between 16th November 2015 to 29th February 2016. The questionnaire was
anonymous, on-line self-administered survey. Statistical analysis were performed
using STATA/SE 12 software. The response rate was 28.91% (n = 72/249). Among the
studied population 76.39% (n = 55) had never performed influenza vaccine during
the previous 5 years. Regarding source of information, only 15.28% of the
subjects (n = 11) consulted the scientific publications, vs 52.78% (n = 38) who
did not show any kind of interest upon the influenza vaccine. Our results show a
low attitude to be vaccinated among pharmacists together with a low grade of
awareness regarding the important role that pharmacists might play in order to
reduce influenza burden, to promote health literacy among their patients and to
decrease the risk of patients infection. Pharmacists might be crucial healthcare
workers involved in health promotion, in vaccines' uptake and practices
progression.
PMID- 29938236
TI - Perceived barriers to breast cancer screening among Saudi women at primary care
setting.
AB - Introduction: Screening for breast cancer (BC) is of low rate in Saudi Arabia;
although it is provided in the country free of charge to the population. This
cross-sectional study aimed at investigating the perceived barriers towards BC
screening in Al Hassa, Saudi Arabia.Participants and methods. A total of 816
adult Saudi women aged >= 30 years attending for routine primary health services
or accompanying patients at the selected primary health care centers (PHCs) were
randomly selected from 12 PHCs (8 urban and four rural) using multi-stage
sampling method. Participants were invited to personal interview using semi
structured data collection instrument including inquiries about socio
demographics, reproductive history, previous histories of diagnosed breast
lesions and breast cancer. The perceived individual barriers towards screening,
their attitudes, the reasons for not attending previously held screening
campaigns in Al Hassa, were also included. Results: Low utilization of BC
screening being significantly positively associated with woman's age, higher
educational status, higher family income, using hormonal contraception and
positive history of previous breast as shown by the results of the logistic
regression model. Exploratory factor analysis showed that personal fears
(especially fear of doctors/examiners, fear of hospitals and health facilities
and fear of consequences/results) were the major factors that hinder women from
utilizing the free of charge BC screening with high loading eigenvalue of 3.335,
explaining 30.4% of the barriers. Conclusions: Educational interventions aim at
improving breast cancer knowledge and addressing barriers should be incorporated
as core component of the screening program in Saudi Arabia.
PMID- 29938237
TI - Awareness and knowledge about cervical cancer prevention methods among Tunisian
women.
AB - Introduction: Epidemiological and biological arguments put papillomavirus
infection (HPV) as a determining factor in the etiology of cervical cancer. The
main objective of this study is to assess the knowledge, attitudes and practices
related to HPV prevention and cervical cancer screening among women living in the
city of Sousse, Tunisia. Methods: Five hundred Tunisian women were interviewed
face to face between May and June 2016. The questionnaire consisted in 14
questions relating participants' socio-demographic information, their awareness
level, attitudes and practices regarding HPV and cervical cancer, including their
understanding of the underlying cervical cancer etiology and preventive actions
such as the Pap Smear test, and finally their acceptability and willingness to
receive the anti-HPV vaccine under certain circumstances. Multivariate analyses
were conducted to identify predictive factors of good acceptability of cervical
cancer prevention methods. Results: Four hundred fifty-two questionnaires were
completed and included in the analysis. The awareness of a sexually transmitted
infection as an etiological agent for cervical cancer was expressed by 175
(38.7%) participants, the correct finality of the Pap Smear test by 308 (68%) and
its recommended frequency by 176 (38.9%) respondents. Among all participants, 125
(27.7%) had undertaken the Pap Smear test at least once in their lifetime, 363
(80.3%) were interested in receiving the anti-HPV vaccine for themselves, 387
(86%) for their daughters and 405 (90%) approved the introduction of the anti-HPV
vaccine in the Tunisian national program of vaccination. Conclusions: The
knowledge and awareness of HPV infection and cervical cancer among Tunisian women
was found to be moderate (around 40%) and the acceptability of the anti-HPV
vaccine was found to be high (over 80%). These results are concordant with the
results of other studies conducted in other MENA countries.
PMID- 29938238
TI - Current data in Greek children indicate decreasing trends of obesity in the
transition from childhood to adolescence; results from the National Action for
Children's Health (EYZHN) program.
AB - Introduction: The aim of the study is to present the most recent estimates of
obesity (total and central) prevalence in Greek children and associated risk
factors. Methods: Population data are derived from a yearly, school-based health
survey polled in 2015 on 336,014 (51% boys) children aged 4 to 17 years old from
almost 40% of all schools of primary and secondary education in Greece.
Anthropometric and physical fitness measurements were obtained by trained
investigators. Dietary habits, physical activity status, sedentary activities and
sleeping hours were assessed through self-completed questionnaires. The gender
and age-specific Body Mass Index (BMI) cut-off points were used in order to
define BMI groups. Results: The prevalence of overweight and obesity in the whole
population was 22.2% and 9.0% in boys and 21.6% and 7.5% in girls, respectively.
Obesity presented decreasing trends in the transition from childhood to
adolescence. Central obesity was diagnosed in 95.3% and 93.5% of the simple obese
boys and girls, respectively, in almost two to three of overweight children
(68.6% of boys and 64.3% of girls), and in 12% of normal weight children. Age,
physical fitness, low adherence to Mediterranean diet, insufficient sleeping
hours, inadequate physical activity levels and increased screen time were all
associated with higher odds of total and central obesity. Conclusions: Serious
and urgent actions need to be taken from public health policy makers in order not
only to prevent a further increase in obesity rates but, more important, to treat
obesity and/or the obesity associated co-morbidities.
PMID- 29938239
TI - A screening focusing on aftereffects of alcohol consumption in a student
population. A National cross-sectional survey.
AB - Introduction: Students overestimate alcohol consumption of those around them and
underestimate their own, so that quantitative approach may not be the most
relevant to assess students' drinking. The main objective was to provide an
appropriate tool for screening for students with potential drinking problems.
Methods: A multicentre cross-sectional survey was conducted by internet between
February and June, 2013 in France. Thirteen questions explored alcohol
consumption, including 8 concerning after-effects of drinking episodes (4 items
of the AUDIT) and alcohol behaviour (CAGE test). A multiple correspondence
analysis (MCA) was conducted to identify profiles of student's alcohol
consumption. Partitioning methods were used to group students by mode of alcohol
use. The most relevant items included in the MCA were identified. Three questions
were identified as most pertinent among the students with potential drinking
problems and ranked by a decision tree with the Chi-square Automatic Interaction
Detector method. Finally, we assessed the generalisation of the model. Results: A
total of 36,427 students participated in the survey: 25,679 were women (70.5% of
respondents), sex ratio 0.42 and mean aged 21.2 (sd 3.7 years). Among those who
had experimented with alcohol (N = 33,113), three consumption profiles were
identified: "simple/non-use" (66.9%), "intermediate consumption" (25.9%) and
"problem drinking" (7.2%). For the latter group, the three most relevant items
were (Q20) "not able to stop drinking after starting", (Q21) "failed to do what
was normally expected", and (Q23) "unable to remember what happened the night
before". Conclusions: These results provide healthcare professionals with a 3
item screening tool for students "problem drinking".
PMID- 29938240
TI - Energy drink and ginseng consumption by Italian university students: a cross
sectional study.
AB - Introduction: The consumption of energy drinks (ED) and ginseng by young people
to enhance their mental and physical performance has become widespread. Reported
side-effects of ED have raised doubts regarding their safety. This cross
sectional study investigates the phenomenon. Methods: An anonymous questionnaire
was administered to a representative sample of Verona university students. The
resulting data were analyzed with Excel 2013, STATA 13 software. Results: ED and
ginseng consumption was reported by 38.6% and 37.4% of the students,
respectively. More than 70% of ED and ginseng users were 18 to 22 years old.
Excluding non-responders, ED consumers were mostly males (51.8% vs 33.0%),
contrary to ginseng consumers (females 40.4% vs 30.9%). Being a working student
was significantly positively associated both to EDs (OR 1.5) and ginseng use (OR
1.4). The most frequently reported academic and other reasons for ED use were:
"to study longer" (47.5%), and "to socialize" (29.1%). The most often used
combinations were ED containing alcohol (65.6%) and ginseng-coffee beverages
(71.8%). Conclusions: The diffusion of ED and ginseng consumption warrants
prevention and monitoring measures, and deserves further analysis.
PMID- 29938241
TI - Energy drink consumption: a survey in high school students and associated
psychological effects.
AB - Introduction: Energy drinks represent an emerging health problem among young
people. Energy drinks generally refer to a class of beverages containing sugars
and various combinations of bioactive ingredients such as caffeine, taurine etc.
Also the mix of energy drinks with alcohol is fairly frequent among young people
and could be associated with dangerous effects. Methods: In 2016-2017, a cross
sectional study was conducted in 1581 students attending eight high school in the
Marche Region. Data were collected via an anonymous self-administered
questionnaire. Results: The 27.7% of students use energy drinks and the majority,
corresponding with the 93.0%, are aware of the main ingredients contained in
energy drinks. The main activities for which young people use these drinks are:
sport, leisure, pleasure, study. Young people who admit to using alcohol mixed
with energy drinks more than 4 times a month are an alarming fact. Conclusions:
This research confirms that energy drinks are used more by young males and
especially by those who practice sports. Furthermore, the use these beverages to
increase the concentration in the study and to be more brilliant in free time, is
confirmed.
PMID- 29938242
TI - Mental and physical effects of energy drinks consumption in an Italian young
people group: a pilot study.
AB - Introduction: The primary consumers of energy drinks were athletes, to combat
fatigue, but in reality, thanks to their fast expansion and economic growth,
young adults and teenagers represent the new target market. Consumption of energy
drinks by both recreational and competitive athletes has increased dramatically
in recent years, though they are often unaware of what is being ingested,
believing to improve their physical and psychological performance. The literature
shows contradictions about the capacity of energy drinks to enhance
psychophysical results. In relation to probable adverse effects induced by the
irregular consumption of energy drinks, which in several cases are not so clear,
we decided to investigate the possible relationship between the intake of energy
drinks and the presence of mental and physical stress in young people and
athletes. Methods: Two experimental sessions, separated at least by 1 week,
according to a randomized cross-over design, following this protocol were
conducted: in the first session a mental and physical stress was conducted
without the consumption of energy drinks, the second after energy drinks
consumption. BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory II)
test have been used to test the mental stress, and a "cycle ergometer test" to
test the physical stress. Results: BAI and BDI tests results showed that before
the consumption of energy drinks, subjects are considered in the range of
"minimal level of anxiety", (10 and 60 percentiles) and do not report a level of
depression. After the energy drinks consumption, a "mild level of anxiety" has
been recorded, and the BDI showed a case with a pathological profile. The
physical test recorded a small increase in the maximum heart rate was verified
with the intake of an energetic beverage. Conclusions: The stimulating effect of
Energy Drinks EDs on nervous system and cardiovascular system, must be checked
and studied in deeper detail, because it may represent a risk for the health of
young athletes.
PMID- 29938243
TI - Effects of anticoagulation therapy with vitamin K antagonists on hospitalizations
and emergency room accesses in Grosseto (Italy).
AB - Introduction: A lot of drug groups are associated with preventable drug-related
admissions. Coumarin derivatives, prescribed for the treatment and prevention of
deep vein thrombosis or pulmonary embolism or prevention of systemic embolism or
stroke in patients with prosthetic heart valves or atrial fibrillation, are often
associated with bleeding. The aim of our study was to analyze how the
anticoagulant therapy with VKAs could affects the hospitalizations and the visits
to emergency room in the elderly population (> 65 years old). Methods: In 2013 we
conducted a cross sectional study analyzing the database of all pharmaceutical
prescriptions, selecting patients living in Grosseto (Italy), which received at
least two prescriptions of coumarin derivatives in 2012. We analyzed the
admissions to hospital and the accesses to the emergency rooms (ERs) made by each
patient, focusing especially on those related to bleeding. For each access to ER
we recorded the date, time of stay, diagnosis and outcome. For each
hospitalization the information we recorded were the date of admission and
discharge diagnosis. Results: 3684 patients were included in our study. 261
(7.1%) patients visited the emergency room for bleeding; 37 (1%) for intracranial
bleeding. The accesses made by men were higher than those made by women. The
average time of stay in ER was 349 minutes. The admissions to hospital were 96
(2.6%); 42 (1.1%) were admitted to hospital with a diagnosis of major vascular
event. 53 patients (20.3%), accessed to the ER more than one time. The 11.5% was
admitted to the hospital more than one time. Conclusions: Our study showed that
VKAs are responsible of an increase of the accesses to ER and of the admissions
to hospital. However, it would be interesting to enlarge the sample size
including patients living in other provinces or in other regions, with a lower
age and treated also with TSOACs, in order to evaluate the real cost
effectiveness of anticoagulant therapy.
PMID- 29938244
TI - Knowledge, attitude and practice about leptospirosis prevention among town
service workers in northeastern Malaysia: a cross sectional study.
AB - Introduction: Many efforts have been done to reduce leptospirosis infections in
Malaysia especially among high risk groups including town service workers. Town
service workers are more likely to be exposed to the leptospiral infection
resulting from their occupational activities. Methods: A cross sectional study
was conducted in northeastern Malaysia involving 321 town service workers who
were subjected to answer an interviewer-guided validated questionnaire which
consists of sociodemographic, knowledge, attitude and practice information. Data
were entered and analyzed using SPSS Version 20. Results: All of the respondents
were Malay with mean (SD) age of 40.6 (10.28) years old. The mean (SD) duration
of employment was 12.1 (9.62) years. Fifty four respondents (16.8%) had never
heard of leptospirosis. Among the respondents, 215 (67.0%) of them had poor
knowledge on leptospirosis. Meanwhile, 167 (52.0%) and only 128 (39.9%) of them
had satisfactory attitude and practice respectively. It was found that knowledge
on risk factors for leptospirosis was lacking. There were high risk attitudes
such as drinking habit and protective equipment used during working with the
favourable answers ranged from 67.3% to 89.1%. The weakest area identified in
their practice was also on the use of protective equipment. Conclusions: The
workers' level of knowledge and practice were relatively poor despite an overall
good practice on leptospirosis. This finding might expose them to an increased
risk of contracting leptospirosis. Identified weak areas in their knowledge,
attitude and practice will assist the policy makers to develop a focused and well
directed intervention program on leptospirosis infection.
PMID- 29938245
TI - Overview of Japanese encephalitis disease and its prevention. Focus on IC51
vaccine (IXIARO(r)).
AB - Japanese encephalitis (JE) is a vector-borne disease caused by the Japanese
encephalitis virus (JEV). JEV is transmitted by mosquitoes to a wide range of
vertebrate hosts, including birds and mammals. Domestic animals, especially pigs,
are generally implicated as reservoirs of the virus, while humans are not part of
the natural transmission cycle and cannot pass the virus to other hosts. Although
JEV infection is very common in endemic areas (many countries in Asia), less than
1% of people affected develop clinical disease, and severe disease affects about
1 case per 250 JEV infections. Although rare, severe disease can be devastating;
among the 30,000-50,000 global cases per year, approximately 20-30% of patients
die and 30-50% of survivors develop significant neurological sequelae. JE is a
significant public health problem for residents in endemic areas and may
constitute a substantial risk for travelers to these areas. The epidemiology of
JE and its risk to travelers have changed, and continue to evolve. The rapid
economic growth of Asian countries has led to a surge in both inbound and
outbound travel, making Asia the second most-visited region in the world after
Europe, with 279 million international travelers in 2015. The top destination is
China, followed by Thailand, Hong Kong, Malaysia and Japan, and the number of
travelers is forecast to reach 535 million by 2030 (+ 4.9% per year). Because of
the lack of treatment and the infeasibility of eliminating the vector,
vaccination is recognized as the most efficacious means of preventing JE. The
IC51 vaccine (IXIARO(r)) is a purified, inactivated, whole virus vaccine against
JE. It is safe, well tolerated, efficacious and can be administered to children,
adults and the elderly. The vaccination schedule involves administering 2 doses
four weeks apart. For adults, a rapid schedule (0-7 days) is available, which
could greatly enhance the feasibility of its use. Healthcare workers should
inform both short- and long-term travelers of the risk of JE in each period of
the year and recommend vaccination. Indeed, it has been shown that short-term
travelers are also at risk, not only in rural environments, but also in cities
and coastal towns, especially in tourist localities where excursions to country
areas are organized.
PMID- 29938246
TI - The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular
Disease.
AB - The B-cell lymphoma 2-associated anthanogene (BAG3) protein is expressed most
prominently in the heart, the skeletal muscle, and in many forms of cancer. In
the heart, it serves as a co-chaperone with heat shock proteins in facilitating
autophagy; binds to B-cell lymphoma 2, resulting in inhibition of apoptosis;
attaches actin to the Z disk, providing structural support for the sarcomere; and
links the alpha-adrenergic receptor with the L-type Ca2+ channel. When BAG3 is
overexpressed in cancer cells, it facilitates prosurvival pathways that lead to
insensitivity to chemotherapy, metastasis, cell migration, and invasiveness. In
contrast, in the heart, mutations in BAG3 have been associated with a variety of
phenotypes, including both hypertrophic/restrictive and dilated cardiomyopathy.
In murine skeletal muscle and vasculature, a mutation in BAG3 leads to critical
limb ischemia after femoral artery ligation. An understanding of the biology of
BAG3 is relevant because it may provide a therapeutic target in patients with
both cardiac and skeletal muscle disease.
PMID- 29938247
TI - Baseline Predictors for Five-Year Visual Acuity Outcomes in the Comparison of AMD
Treatment Trials.
AB - Purpose: To determine baseline predictors of visual acuity (VA) outcomes at 5
years after initiating treatment with ranibizumab or bevacizumab for neovascular
age-related macular degeneration (AMD). Design: Secondary analysis of data from a
cohort study. Participants: Patients enrolled in the Comparison of AMD Treatments
Trials (CATT) who completed a 5-year follow-up visit. Methods: Participants were
randomly assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens.
After two years, patients were released from the clinical trial protocol, and
were recalled for examination at 5 years. Trained readers evaluated baseline
lesion features, fluid and thickness. Baseline predictors were determined using
univariate and multivariate regression analysis. Main Outcome Measures: VA score
and change from baseline, >=3-line gain, and VA 20/200 or worse at 5 years.
Results: Among 647 patients with VA measured at 5 years, mean VA score in the
study eye was 58.9 letters (~20/63), mean decrease from baseline was 3.3 letters,
17.6% eyes gained >=3 lines, and 19.9% had VA of 20/200 or worse. In multivariate
analysis, worse baseline VA was associated with worse VA, more VA gain, higher
percentage with >=3-line gain, and higher percentage with 20/200 or worse at 5
years (all p<0.001). Larger baseline CNV lesion area was associated with worse
VA, greater VA loss, and higher percentage with 20/200 or worse at 5 years (all
p<0.05). Absence of baseline subretinal fluid was associated with worse VA
(p=0.03) and more VA loss (p=0.03). Female gender, bevacizumab treatment in the
first 2 years, and absence of RPE elevation were associated with higher
percentage with >=3-line gain. Cigarette smoking was associated with a higher
percentage with 20/200 or worse. None of the 21 SNPs evaluated were associated
with VA outcomes. Conclusions: Five years after initiating treatment with
ranibizumab or bevacizumab in CATT participants, worse baseline VA, larger
baseline CNV lesion area, and presence of baseline RPE elevation remained
independently associated with worse VA at 5 years. In addition, male gender,
cigarette smoking, absence of subretinal fluid and treatment with ranibizumab in
the first 2 years were independently associated with worse vision outcomes at 5
years.
PMID- 29938248
TI - Charcoal Disrupts Soil Microbial Communication through a Combination of Signal
Sorption and Hydrolysis.
AB - The presence of charcoal in soil triggers a range of biological effects that are
not yet predictable, in part because it interferes with the functioning of
chemical signals that microbes release into their environment to communicate. We
do not fully understand the mechanisms by which charcoal alters the biologically
available concentrations of these intercellular signals. Recently, charcoal has
been shown to sorb the signaling molecules that microbes release, rendering them
ineffective for intercellular communication. Here, we investigate a second,
potentially more important mechanism of interference: signaling-molecule
hydrolysis driven by charcoal-induced soil pH changes. We examined the effects of
10 charcoals on the bioavailable concentration of an acyl-homoserine lactone
(AHL) used by many Gram-negative bacteria for cell-cell communication. We show
that charcoals decrease the level of bioavailable AHL through sorption and pH
dependent hydrolysis of the lactone ring. We then built a quantitative model that
predicts the half-lives of different microbial signaling compounds in the
presence of charcoals varying in pH and surface area. Our model results suggest
that the chemical effects of charcoal on pH-sensitive bacterial AHL signals will
be fundamentally distinct from effects on pH-insensitive fungal signals,
potentially leading to shifts in microbial community structures.
PMID- 29938251
TI - Do the labour market returns to university degrees differ between high and low
achieving youth? Evidence from Australia.
AB - In almost all developed countries there has been substantial growth in university
education over the last half-century. This growth has raised concerns that the
benefits of university education are declining and that university education is
not appropriate for students who, without the expansion, would not have been
admitted. For such students, vocational education or direct entry to the labour
market may be more appropriate. The purpose of this study is to examine the
effects of university and vocational qualifications, net of other influences on a
variety of labour market outcomes for Australian youths up to age 25; and if the
benefits of university degrees differ across the achievement continuum.
Achievement is measured by test scores in the OECD's PISA assessments. The six
labour market outcomes investigated are: occupational status, hourly and weekly
earnings, employment, unemployment and full-time work. The study finds that
university degrees provide substantially superior labour market outcomes which
are not confined to high and average achievers, at least for this cohort in their
formative years in the labour market.
PMID- 29938249
TI - Duodenal-Jejunal Flexure GI Stromal Tumor Frequently Heralds Somatic NF1 and
Notch Pathway Mutations.
AB - Purpose: GI stromal tumors (GISTs) are commonly associated with somatic mutations
in KIT and PDGFRA. However, a subset arises from mutations in NF1, most commonly
associated with neurofibromatosis type 1. We define the anatomic distribution of
NF1 alterations in GIST. Methods: We describe the demographic/clinicopathologic
features of 177 patients from two institutions whose GISTs underwent next
generation sequencing of >=315 cancer-related genes. Results: We initially
identified six (9.7%) of 62 GISTs with NF1 genomic alterations from the first
cohort. Of these six patients, five (83.3%) had unifocal tumors at the duodenal
jejunal flexure (DJF). Two additional patients with DJF GISTs had non-NF1 (KIT
and BRAF) genomic alterations. After excluding one DJF GIST with an NF1 single
nucleotide polymorphism, four (57.1%) of seven sequenced DJF tumors demonstrated
deleterious NF1 alterations, whereas only one (1.8%) of 55 sequenced non-DJF
GISTs had a deleterious NF1 somatic mutation (P < .001). One patient with DJF
GIST had a germline NF1 variant that was associated with incomplete penetrance of
clinical neurofibromatosis type 1 features along with a somatic NF1 mutation. Of
the five DJF GISTs with any NF1 alteration, three (60%) had KIT mutations, and
three (60%) had Notch pathway mutations (NOTCH2, MAML2, CDC73). We validated
these findings in a second cohort of 115 GISTs, where two (40%) of five unifocal
NF1-mutated GISTs arose at the DJF, and one of these also had a Notch pathway
mutation (EP300). Conclusion: Broad genomic profiling of adult GISTs has revealed
that NF1 alterations are enriched in DJF GISTs. These tumors also may harbor
concurrent activating KIT and/or inactivating Notch pathway mutations. In some
cases, germline NF1 genetic testing may be appropriate for patients with DJF
GISTs.
PMID- 29938252
TI - Urokinase-type Plasminogen Activator Promotes Synaptic Recovery in the Ischemic
Brain.
AB - Synaptic dysfunction underlies the development of neurological impairment
following an acute ischemic stroke. Unfortunately, to this date there is no
therapeutic approach to protect and repair the synapse that has suffered an
ischemic injury. However, recent research with in vitro models of hypoxia, in
vivo models of cerebral ischemia and different neuroradiological techniques has
revealed that during the recovery phase from a hypoxic injury neurons release the
serine proteinase urokinase-type plasminogen activator (uPA) and astrocytes
recruit its receptor (uPAR) to their plasma membrane; and that binding of
neuronal uPA to astrocytic uPAR promotes the recovery of the "tripartite synapse"
that has suffered an acute ischemic injury. The translational relevance of these
findings is underscored by the fact that intravenous treatment with recombinant
uPA promotes synaptic recovery and functional improvement following an acute
ischemic stroke.
PMID- 29938253
TI - 3D-2D heterostructure of PdRu/NiZn oxyphosphides with improved durability for
electrocatalytic methanol and ethanol oxidation.
AB - The rational design and engineering of bimetallic Pd-based nanocatalysts with
both high activity and durability are of paramount significance for the practical
applications of fuel cells. Herein, a new class of well-defined 2D NiZn
oxyphosphide nanosheets (NiZnP NSs) have been successfully engineered to support
unique 3D PdRu nanoflowers (PdRu NFs) via a facile strategy. Such nanohybrids
with abundant surface active areas and modified electronic structure exhibit a
great enhancement in electrocatalytic activity for the methanol oxidation
reaction (MOR) and ethanol oxidation reaction (EOR), whose mass/specific
activities are 1739.5 mA mg-1/4.5 mA cm-2 and 4719.8 mA mg-1/12.3 mA cm-2, which
are 8.3/9.0 and 8.3/9.5 times higher than those of commercial Pd/C catalysts,
respectively. More interestingly, with the remarkable promotional effect of NiZnP
NSs, such 3D-2D PdRu/NiZn oxyphosphide nanohybrids can even retain 72.4% and
70.1% of initial catalytic activity toward MOR and EOR for 1000 potential cycles
with negligible morphological or compositional variations. The successful
construction of this new class of electrocatalysts opens up a new way for
designing 3D-2D nanohybrids with high performance for electrochemical reactions
and beyond.
PMID- 29938250
TI - Use of Mobile Devices to Measure Outcomes in Clinical Research, 2010-2016: A
Systematic Literature Review.
AB - Background: The use of mobile devices in clinical research has advanced
substantially in recent years due to the rapid pace of technology development.
With an overall aim of informing the future use of mobile devices in
interventional clinical research to measure primary outcomes, we conducted a
systematic review of the use of and clinical outcomes measured by mobile devices
(mobile outcomes) in observational and interventional clinical research. Method:
We conducted a PubMed search using a range of search terms to retrieve peer
reviewed articles on clinical research published between January 2010 and May
2016 in which mobile devices were used to measure study outcomes. We screened
each publication for specific inclusion and exclusion criteria. We then
identified and qualitatively summarized the use of mobile outcome assessments in
clinical research, including the type and design of the study, therapeutic focus,
type of mobile device(s) used, and specific mobile outcomes reported. Results:
The search retrieved 2,530 potential articles of interest. After screening, 88
publications remained. Twenty-five percent of the publications (n = 22) described
mobile outcomes used in interventional research, and the rest (n = 66) described
observational clinical research. Thirteen therapeutic areas were represented.
Five categories of mobile devices were identified: (1) inertial sensors, (2)
biosensors, (3) pressure sensors and walkways, (4) medication adherence monitors,
and (5) location monitors; inertial sensors/accelerometers were most common
(reported in 86% of the publications). Among the variety of mobile outcomes,
various assessments of physical activity were most common (reported in 74% of the
publications). Other mobile outcomes included assessments of sleep, mobility, and
pill adherence, as well as biomarkers assessed using a mobile device, including
cardiac measures, glucose, gastric reflux, respiratory measures, and intensity of
head-related injury. Conclusion: Mobile devices are being widely used in clinical
research to assess outcomes, although their use in interventional research to
assess therapeutic effectiveness is limited. For mobile devices to be used more
frequently in pivotal interventional research - such as trials informing
regulatory decision-making - more focus should be placed on: (1) consolidating
the evidence supporting the clinical meaningfulness of specific mobile outcomes,
and (2) standardizing the use of mobile devices in clinical research to measure
specific mobile outcomes (e.g., data capture frequencies, placement of device).
To that aim, this manuscript offers a broad overview of the various mobile
outcome assessments currently used in observational and interventional research,
and categorizes and consolidates this information for researchers interested in
using mobile devices to assess outcomes in interventional research.
PMID- 29938254
TI - Eliminating the solvent blocking requirement of interconnection layers in polymer
tandem solar cells by thin-film transfer technique.
AB - Interconnection layers (ICLs) for polymer tandem solar cells reported so far are
limited in materials' choice and layer structure, because of a requirement that
the ICLs must prevent the penetration of solvents used for the top cells. In this
research, it is demonstrated that depositing the active layer of the top subcell
using a dry thin-film transfer technique allows for incorporation of an ICL
composed of vacuum deposited materials in a polymer tandem cell, providing a
large degree of freedom in ICL design. Specifically, a polymer tandem solar cell
was fabricated using an ICL composed of bathocuproine:silver/silver
islands/1,4,5,8,9,11-hexaazatriphenylene hexacarbonitrile (BCP:Ag/Ag islands/HAT
CN), where the thicknesses of the BCP:Ag and Ag island layers are precisely
controlled at the nanoscale to facilitate the transport of electrons generated in
the bottom subcell and to ensure their efficient recombination with holes
generated in the top subcell. Consequently, the tandem device featuring the
optimized ICL, whose active layers are composed of poly(3-hexylthiophene):[6,6]
phenyl-C61-butyric acid methyl ester (P3HT:PC61BM) and poly[2,6-(4,4-bis-(2
ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3
benzothiadiazole)]:[6,6]-phenyl-C71-butyric acid methyl ester (PCPDTBT:PC71BM),
exhibits an open-circuit voltage of 1.20 V, which is equal to the sum of the open
circuit voltages of the two subcells, with a fill factor (FF) of 0.60 almost
identical to the FFs of the subcells.
PMID- 29938255
TI - Chemical sensing with 2D materials.
AB - During the last decade, two-dimensional materials (2DMs) have attracted great
attention due to their unique chemical and physical properties, which make them
appealing platforms for diverse applications in opto-electronic devices, energy
generation and storage, and sensing. Among their various extraordinary
properties, 2DMs possess high surface area-to-volume ratios and ultra-high
surface sensitivity to the environment, which are key characteristics for
applications in chemical sensing. Furthermore, 2DMs' superior electrical and
optical properties, combined with their excellent mechanical characteristics such
as robustness and flexibility, make these materials ideal components for the
fabrication of a new generation of high-performance chemical sensors. Depending
on the specific device, 2DMs can be tailored to interact with various chemical
species at the non-covalent level, making them powerful platforms for fabricating
devices exhibiting a high sensitivity towards detection of various analytes
including gases, ions and small biomolecules. Here, we will review the most
enlightening recent advances in the field of chemical sensors based on atomically
thin 2DMs and we will discuss the opportunities and the challenges towards the
realization of novel hybrid materials and sensing devices.
PMID- 29938256
TI - Influence of the Ge distribution on the first order magnetic transition of the
MnFe(P,Ge) magnetocaloric material.
AB - MnFe(P,Ge) is a promising magnetocaloric material for potential refrigeration
applications near room temperature. However, its relatively large hysteresis and
large temperature/field range of two-phase [paramagnetic (PM) and ferromagnetic
(FM)] coexistence displayed in the cyclic first order magnetic transition (FOMT)
cause energy losses and reduce the energy conversion efficiency. In this work, we
explore the underlying causes of phase coexistence, hysteresis and structural
transformation based on determination of the Ge distribution in MnFeP1-xGex (0.10
< x < 0.50) materials. We find that all the samples crystallize in the Fe2P-type
structure [P6[combining macron]2m (No. 189), Z = 3] and Ge displays a strong
preference for the 2c site. First principles total energy calculations confirm
this site preference of Ge, and Ge entering the 2c site changes the electronic
structures and enhances the Fe and Mn 3d exchange splitting across the Fermi
level as well as the FM exchange interactions, consequently leading to a linear
increase in the transition temperature with increasing Ge content. Scanning
electron microscopy and energy-dispersive spectroscopy reveal the inhomogeneous
distribution of Ge in grains, which makes the grains with larger Ge content
transform from the PM to the FM phase first when cooling and thus causes the
phase coexistence. Maximum entropy method electron-densities show that weakening
the coplanar Fe-P/Ge(2c) and Mn-P(1b) bonding strengths across the PM to FM phase
transition can release some 3d-electrons to enhance the Fe-Mn FM exchange
interaction and result in coupling between the magnetic and structural degrees of
freedom. This provides first direct evidence for the dominant role of Fe-Mn
exchange interaction in the ferromagnetic ordering and may provide a method to
observe the exchange interaction. Diminishing the variances in covalent bonding
strengths across the FOMT gives rise to an exponential decay in the heat
hysteresis when increasing the Ge occupancy at the 2c site. To the best of our
knowledge, this is the first time a relationship between the variances in
covalent bonding strengths and hysteresis is proposed. This material thus
provides an example of a FOMT and hysteresis driven by reversible weakening and
strengthening of covalent bonds. Based on these, a strategy of designing better
magnetocaloric materials is suggested.
PMID- 29938258
TI - Two-dimensional pentagonal CrX (X = S, Se or Te) monolayers: antiferromagnetic
semiconductors for spintronics and photocatalysts.
AB - Two dimensional (2D) materials with hexagonal building blocks have received
tremendous interest in recent years and show promise as nanoscale devices for
versatile applications. Herein, we propose a new family of 2D pentagonal CrX (X =
S, Se or Te) monolayers (penta-CrX) for applications in electronics, spintronics
and photocatalysis. We find that the 2D penta-CrX monolayers are thermally,
structurally and mechanically stable. The penta-CrX monolayers are
antiferromagnetic and semiconducting. We show that the magnetism is attributed to
the super-exchange induced by the ionic interactions between the Cr and X atoms
and can be enhanced upon applying tension. We further show that the penta-CrS and
penta-CrSe monolayers show good redox potentials versus a normal hydrogen
electrode, and their band gaps are comparable to the energy of a photon in the
visible light region, indicating their capability of maximal utilization of solar
energy for water splitting. With intrinsic semiconducting and controllable
magnetic properties, the proposed penta-CrX monolayers may hold promise as
flexible spintronics and photocatalysts.
PMID- 29938257
TI - Anti-thrombotic strategies for microfluidic blood processing.
AB - The redundant mechanisms involved in blood coagulation are crucial for rapid
hemostasis. Yet they also create challenges in blood processing in medical
devices and lab-on-a-chip systems. In this work, we investigate the effects of
both shear stress and hypothermic blood storage on thrombus formation in
microfluidic processing. For fresh blood, thrombosis occurs only at high shear,
and the glycoprotein IIb/IIIa inhibitor tirofiban is highly effective in
preventing thrombus formation. Blood storage generally activates platelets and
primes them towards thrombosis via multiple mechanisms. Thrombus formation of
stored blood at low shear can be adequately inhibited by glycoprotein IIb/IIIa
inhibitors. At high shear, von Willebrand factor-mediated thrombosis contributes
significantly and requires additional treatments with thiol-containing
antioxidants-such as N acetylcysteine and reduced glutathione-that interfere with
von Willebrand factor polymerization. We further demonstrate the effectiveness of
these anti-thrombotic strategies in microfluidic devices made of cyclic olefin
copolymer, a popular material used in the healthcare industry. This work
identifies effective anti-thrombotic strategies that are applicable in a wide
range of blood- and organ-on-a-chip applications.
PMID- 29938259
TI - Tuneable spheroidal hydrogel particles for cell and drug encapsulation.
AB - The need to better mimic native tissues has accompanied research in tissue
engineering and controlled drug delivery. The development of new platforms for
cell and drug encapsulation followed the same trend, and studying the influence
of the delivery material system's geometry has been gaining momentum. Aiming to
investigate how an increase in surface area and varying particle shape could
impact drug release and cell viability, a novel method was developed to produce
spheroidal hydrogel particles with adjustable circularity, aiming to tune drug
delivery. For this purpose, droplets of hydrogel precursor were squeezed between
two superamphiphobic surfaces separated with spacers with different height, and
then photo-crosslinked to maintain the acquired shape after "de-sandwiching".
Numerical modelling studies were performed to study the polymeric droplet
geometry deformation process, which were consistent with experimentally obtained
results. The spheroidal particles were produced under mild conditions using
methacrylated chitosan, capable of encapsulating proteins or cells. Likely due to
their higher surface area to volume-ratio, compared to spherical-shaped ones,
spheroids presented an improved viability of encapsulated cells due to enhanced
nutrient diffusion to the core, and led to a significantly faster drug release
rate from the polymer network. These results were also assessed numerically, in
which the drug release rate was computed for different spheroidal-like
geometries. Hence, the described method can be used to manufacture spheroidal
particles with tailored geometry that can be broadly applied in the biomedical
field, including for drug delivery or as cell encapsulation platforms.
PMID- 29938260
TI - A computationally-derived model for the solvatochromism of p-phenolates with high
predictive power.
AB - We report that the positive, reverse or negative solvatochromism of p-phenolate
based dyes is highly correlated with the multireferential (MR) character of their
ground-state wave function, with negative compounds presenting the highest
degeneracy. CASSCF/NEVPT2 calculations show that the high MR character of the
wave-function in negative dyes allows those systems to increase the dipole moment
of the ground state by breaking the degeneracy as a response to the field of a
polar solvent. The resulting stabilization of the ground-state with increasing
solvent polarity leads to the observed negative solvatochromic behavior. A
computational indicator based on our results has been successfully used for
determining the direction of the solvatochromic shift of 24 dyes. Thus, our work
sheds light on the physical-chemical basis for solvatochromism while providing
experimental chemists with a practical tool for the design of novel negative,
positive or reverse solvatochromic dyes.
PMID- 29938261
TI - Switching on the proton transport pathway of a lanthanide metal-organic framework
by one-pot loading of tetraethylene glycol for high proton conduction.
AB - A one-pot hydrothermal approach has been developed to introduce tetraethylene
glycol (TEG) molecules into a two-dimensional (2D) layered lanthanide metal
organic framework ([Sm(H5C2P2O7)(H2O)2].Guest, denoted SmHEDP-Guest). Through the
straightforward loading of TEG, the proton conductivity of SmHEDP-TEG (1.21 * 10
3 S cm-1) is increased by 3 orders of magnitude compared with its analogue SmHEDP
H2O (1.22 * 10-6 S cm-1) under 100% relative humidity at room temperature. More
excitingly, SmHEDP-TEG exhibits very high proton conductivity of 9.17 * 10-2 S cm
1, even higher than commercial Nafion, when the temperature is increased to 333
K, which is significantly higher than SmHEDP-H2O (3.38 * 10-5 S cm-1). The single
crystal XRD reveals that the adjacent water molecules located in the channels of
SmHEDP-H2O are isolated without hydrogen bonding interactions owing to their long
distances. However, interestingly, the guest TEG molecules of SmHEDP-TEG behave
as hydrogen bonded connected bridges, which switch on the proton transport
pathway to promote proton hopping. This discovery may provide a facile strategy
to design and synthesize more promising candidates for novel proton conductors.
PMID- 29938262
TI - Layered ferrimagnets constructed from charge-transferred paddlewheel [Ru2] units
and TCNQ derivatives: the importance of interlayer translational distance in
determining magnetic ground state.
AB - A donor (D)/acceptor (A) assembly reaction using the paddlewheel-type
diruthenium(ii,ii) complex [Ru2(3,5-F2PhCO2)4(THF)2] (3,5-F2PhCO2- = 3,5
difluorobenzoate; abbreviated hereafter as [Ru2]) as D and 7,7,8,8-tetracyano-p
quinodimethane derivatives (TCNQRx; 2,5-R-substituted TCNQ) as A in a DCM/TCE or
DCE solvent system (DCM = dichloromethane, TCE = 1,1,2,2-tetrachloroethane, DCE =
1,2-dichloroethane) led to the formation of D2A-type two-dimensional layered
compounds [{Ru2(3,5-F2PhCO2)4}2{TCNQRx}].nsolv (Rx = H2 (1), Rx = Me2, (2), and
Rx = (OEt)2 (3)). All the compounds had similar two-dimensional fishnet-type
structures, where the two [Ru2] units were fully coordinated with the four cyano
groups of TCNQRx. The compounds 1-3 were categorized as a one-electron
transferred ionic state (1e-I) with D+-A--D formulation (D+[triple bond, length
as m-dash][RuII,III2]+; A-[triple bond, length as m-dash]TCNQRx-). This subunit
state formally derived a ferrimagnetically ordered state composed of up-spins
with S = 1 for [RuII,II2] and S = 3/2 for [RuII,III2]+ and a down-spin of S = 1/2
for TCNQRx-, with antiferromagnetic superexchange interactions in each layer.
Eventually, 1-3 became three-dimensional ferrimagnets with Curie temperatures TC
= 93, 93, and 92 K, respectively, owing to the presence of interlayer
ferromagnetic interactions. The interlayer translational distances (l2) for the
three compounds were 10.56, 10.54, and 10.84 A, respectively, which agreed with
the empirical prediction based on the threshold value of l2 > 10.3 A for a valid
ferromagnetic interaction.
PMID- 29938263
TI - On the measurement of relaxation times of acoustic vibrations in metal nanowires.
AB - The mechanical resonances of metal nanostructures are strongly affected by their
environment. In this paper the way the breathing modes of single metal nanowires
are damped by liquids with different viscosities was studied by ultrafast pump
probe microscopy experiments. Both nanowires supported on a glass substrate and
nanowires suspended over trenches were investigated. The measured quality factors
for liquid damping for the suspended nanowires are in good agreement with
continuum mechanics calculations for an inviscid fluid that assume continuity in
stress and displacement at the nanowire-liquid interface. This shows that liquid
damping is controlled by radiation of sound waves into the medium. For the
nanowires on the glass surface the quality factors for liquid damping are
approximately 60% higher than those for the suspended nanowires. This is
attributed to a shadowing effect. The nanowires in our measurements have
pentagonal cross-sections. This produces two different breathing modes and also
means that one of the faces for the supported nanowires is blocked by the
substrate, which reduces the amount of damping from the liquid. Comparing the
supported and suspended nanowires also allows us to estimate the effect of the
substrate on the acoustic mode damping. We find that the substrate has a weak
effect, which is attributed to poor mechanical contact between the nanowires and
the substrate.
PMID- 29938264
TI - Dual-catalytic decarbonylation of fatty acid methyl esters to form olefins.
AB - The homogeneous dehydrative decarbonylation of fatty acid methyl esters (FAMEs)
to form olefins is reported. In order to facilitate cleavage of the unactivated
acyl C-O bond of the alkyl ester, a one pot dual-catalytic directing group
strategy was developed through optimization of the individual transesterification
and decarbonylation reaction steps.
PMID- 29938265
TI - Using X-rays in photodynamic therapy: an overview.
AB - Photodynamic therapy is a therapeutic option to treat cancer and other diseases.
PDT is used every day in dermatology, and recent developments in the treatment of
glioblastoma, mesothelioma or prostate have demonstrated the efficacy of this
modality. In order to improve the efficacy of PDT, different strategies are under
development, such as the use of targeted PS or nanoparticles to improve
selectivity and the design of light devices to better monitor the light dose. Due
to the low penetration of light into tissue, another way to improve the efficacy
of PDT to treat deep tumors is the use of upconversion NPs or bi-photon
absorption compounds. These compounds can be excited in the red part of the
spectrum. A relatively new approach, which we will call PDTX, is the use of X
rays instead of UV-visible light for deeper penetration into tissue. The
principle of this technique will be described, and the state-of-art literature
concerning this modality will be discussed. First, we will focus on various
photosensitizers that have been used in combination with X-ray irradiation. To
improve the efficacy of this modality, nanoparticles have been designed that
allow the conversion of high-energy ionizing radiation into UV-visible light;
these are potential candidates for the PDTX approach. They will be discussed at
the end of this review.
PMID- 29938266
TI - Allosteric cooperativity in ternary complexes with low symmetry.
AB - Two new naphthotubes with ester linkers were synthesized and characterized. With
the syn isomers of an ester naphthotube and an ether naphthotube, strong positive
allosteric cooperativity in a ternary complex with two different hosts on one
guest was achieved. This paves the way to construct robust supramolecular
architectures with high complexity and diversity.
PMID- 29938267
TI - Rupture of granular rafts: effects of particle mobility and polydispersity.
AB - Reversible encapsulation of liquid materials is a technical challenge in many
applications such as for the transport and controlled delivery of active
ingredients. In contrast to most state-of-the-art processes, capillary adsorbed
solid particles can achieve chemical-reaction-free encapsulation by forming dense
rafts which isolate the liquid from its surroundings. While the production
conditions of such capsules have been characterized, the control of the armor
robustness remains poorly described and understood. In this paper, we probe the
armor robustness via impacts of droplets on encapsulated materials. Thereby, we
establish the mechanisms and conditions of armor rupture and derive models that
predict the rupturing thresholds or probabilities. Using monodisperse sized
particles and gradually increasing the impacting drop velocity, a sharp
transition from sustained to coalescing drops is observed. On mobile rafts made
of particles at the water/air interface, the velocity threshold increases with
increasing particle diameter while an opposite trend is observed on immobile
rafts made of particles trapped at a gelified interface. Two models based on
particle pair and triplet interactions, respectively, quantitatively match the
experiments. Assembling rafts with particles of two different sizes significantly
smoothens the coalescence transition, regardless of particle mobility. Beyond
apparent similarities, rationalizing the rupturing probability of mobile and
immobile armor evidences very different sensitivity to heterogeneities. On
immobile armor, drop coalescence remains random and thus well described by the
statistical particle distribution while on mobile armor the ruptures are
preferably localized at the non-percolated parts of the granular network.
PMID- 29938268
TI - Asymmetric synthesis of the fully functionalized six-membered ring of trigoxyphin
A.
AB - An asymmetric synthesis strategy of the fully functionalized six-membered ring of
trigoxyphin A, a daphnane-type diterpenoid, has been accomplished concisely from
a d-tartrate derivative. Key elements of this synthesis involve the tandem
ozonization/intramolecular HWE reaction to construct the alpha,beta-unsaturated
cyclohexenone skeleton, the radical cyclization to introduce the C8 chirality and
sequential Kumada cross-coupling/hydroboration-oxidation to introduce the C11
chirality. The target substructure could be synthetically achieved on a multi
gram scale.
PMID- 29938269
TI - A first-principles study of the electrically tunable band gap in few-layer penta
graphene.
AB - The structural and electronic properties of bilayer (AA- and AB-stacked) and tri
layer (AAA-, ABA- and AAB-stacked) penta-graphene (PG) have been investigated in
the framework of density functional theory. The present results demonstrate that
the ground state energy in AB stacking is lower than that in AA stacking, whereas
ABA stacking is found to be the most energetically favorable, followed by AAB and
AAA stackings. All considered model configurations are found to be
semiconducting, independent of the stacking sequence. In the presence of a
perpendicular electric field, their band gaps can be significantly reduced and
completely closed at a specific critical electric field strength, demonstrating a
Stark effect. These findings show that few-layer PG will have tremendous
opportunities to be applied in nanoscale electronic and optoelectronic devices
owing to its tunable band gap.
PMID- 29938270
TI - Artificial sweetener saccharin disrupts intestinal epithelial cells' barrier
function in vitro.
AB - SCOPE: Consumption of non-nutritive sweeteners (NNS) is a dietary practice used
by those who wish to lose weight or by patients on a sugar-restricted diet such
as those with DM2. Although these substances are safe, possible biological
interactions with the digestive tract, particularly in relation to intestinal
permeability, have not been studied. Thus, the current work sought to investigate
the action of different NNS on intestinal permeability using an in vitro Caco-2
cell model. METHODS AND RESULTS: Caco-2 cells were incubated with acesulfame K,
aspartame, saccharin, or sucralose at equimolar concentrations. Acesulfame K,
aspartame, and sucralose did not disrupt monolayer integrity in the cells.
However, saccharin increased paracellular permeability and decreased
transepithelial electrical resistance (TEER) via a non-cytotoxic mechanism. The
levels of the tight junction protein claudin-1 were reduced in Caco-2 cells that
had previously been exposed to saccharin. The inhibition of nuclear factor-kappaB
(NF-kappaB) was able to prevent the reduction in TEER induced by saccharin
treatment. Thalidomide, as an inhibitor of ubiquitin ligase, was able to prevent
the decrease in claudin-1 protein expression and the TEER reduction in Caco-2
cells. CONCLUSIONS: Saccharin disrupts monolayer integrity and alters
paracellular permeability in a Caco-2 cell monolayer model, via a mechanism
involving NF-kappaB activation, resulting in the ubiquitination of the tight
junction protein claudin-1. Saccharin consumption may potentially alter the
intestinal integrity in humans.
PMID- 29938271
TI - Granular chain escape from a pore in a wall in the presence of particles on one
side: a comparison to polymer translocation.
AB - Escape of a granular chain from a pore in a wall in the presence of diffusing
granular particles on one side of the wall is studied experimentally. The escape
time shows power-law behavior as a function of the chain length (tau ? Nalpha). A
Langevin dynamics simulation of a polymer chain in a similar geometry is also
performed and similar results to those for a granular system are obtained. A
simple scaling argument and an energetic argument (based on the Onsager
principle) are introduced which explain our results very well. Experiments
(simulations) show that by increasing the number of particles on one side of the
wall from zero, the exponent alpha decreases from 2.6 +/- 0.1 (3.1 +/- 0.1) to
about 2. Both scaling and the Onsager principle argument predict alpha = 2 at
high particle concentration, in agreement with the experiments and simulations.
In the absence of particles, the scaling predicts tau = N2.5 (in agreement with
the experimental result for the granular chain) and the Onsager principle
predictstau = N3 ln N, supporting the simulation result for the polymer chain.
Experiments, simulations, scaling, and the Onsager principle confirm an inverse
relation between tau and the density of particles on one side of the wall.
PMID- 29938272
TI - Nanomaterials properties tuned by their environment: integrating supramolecular
concepts into sensing devices.
PMID- 29938273
TI - An efficient dye-sensitized NIR emissive lanthanide nanomaterial and its
application in fluorescence-guided peritumoral lymph node dissection.
AB - The luminescence intensity of near-infrared (NIR) emitting lanthanide
nanoparticles (LnNPs) is usually limited, owing to their small absorption cross
section. Although dye sensitization has been proven to be an effective way to
improve the luminescence intensity of LnNPs, the sensitization effect is fairly
limited, owing to the simplicity of the sensitizers used and the complexity of
the energy transfer process, typically involving three steps. In this study, a
more efficient sensitizer (Cy7) was chosen to replace a commonly used one (ICG)
and the energy transfer process was also optimized through using Yb3+ ions as
emitter ions and Nd3+ ions as intermediate ions. With Cy7 as a sensitizer, the
sensitization effect was assessed to be better than with ICG, owing to the higher
quantum yield of Cy7. Meanwhile, the Cy7-sensitized NIR lanthanide nanomaterial
was proven to be good for deep tissue penetration and low-power excitation
bioimaging. Furthermore, the highly-enhanced NIR signal was successfully used in
blood vessel imaging and fluorescence-guided peritumoral lymph node dissection in
a mouse model.
PMID- 29938274
TI - Dynamics of water in conical solvation shells around a benzene solute under
different thermodynamic conditions.
AB - Water molecules in different parts of the anisotropic hydration shell of an
aromatic molecule experience different interactions. In the present study, we
investigate the anisotropic dynamics of water molecules in different non
overlapping conical shells around a benzene solute at sub- and supercritical
conditions by means of molecular dynamics simulations using both non-polarizable
and polarizable models. In addition to the dynamical properties, the effects of
polarizability on the hydration structure of benzene at varying thermodynamic
conditions are also investigated in the current study. The presence of piH
bonding in the solvation shell is found to be an important factor that influences
the anisotropic dynamics of the benzene hydration shell. The water molecules
located axial to the benzene plane are found to be maximally influenced by the
piH-bonding. The extent of piH-bonding is found to be somewhat reduced on
inclusion of polarizability. The piH-bonded water molecules are found to reorient
through large-amplitude angular jumps where the jump-angle amplitude increases at
higher temperatures and lower densities. For both non-polarizable and polarizable
models, it is found that the water molecules in the axial conical shells possess
faster orientational and hydrogen bond dynamics compared to those in the
equatorial plane. Water molecules in the axial conical shells are also found to
diffuse at a faster rate than bulk molecules due to the relatively weaker benzene
water piH-bonding interactions in the axial region of the hydration shell. The
residence dynamics of water molecules in different conical solvation shells
around the solute is also investigated in the current study.
PMID- 29938275
TI - Surface heterogeneity in Li0.5CoO2 within a porous composite electrode.
AB - Surface phase heterogeneity within a fully charged LiCoO2 (LCO) composite
electrode before and after thermal decomposition has been shown to strongly
depend on the distribution of the binder and carbon additives, but be independent
of the crystalline facet and size of LCO, as revealed by X-ray photoemission
electron microscopy (X-PEEM). The obtained new insights deepen the understanding
of thermal stability in a real composite electrode, which would be valuable for
further development of long-life and safe cathodes for lithium-ion batteries.
PMID- 29938276
TI - DNA-templated nanoparticle complexes for photothermal imaging and labeling of
cancer cells.
AB - In situ monitoring of the photothermal (PT) effect at the cellular level is of
great importance in the photothermal (PT) treatment of cancer. Herein, we report
a class of DNA-templated gold nanoparticle (GNP)-quantum dot (QD) complexes (GQC)
for PT sensing in solution and in cancer cells in vitro. Specifically, the QD
photoluminescence (PL) could be activated at elevated temperature with a wide
thermo-responsive range between 45 degrees C and 70 degrees C, which fits the
temperature threshold for effective cancer cell ablation. The general
applicability of GQC for intracellular PT sensing is explored using three types
of PT agents (gold nanorods (GNRs), gold nanostars (GNSs), and Prussian blue
nanoparticles (PBNPs)) with various PT performances. We show that the
intracellular QD PL is gradually activated with increasing near-infrared (NIR)
irradiation time, providing a good correlation with the surrounding medium
temperature for PT sensing. Moreover, we demonstrate that the GQC sensor could be
used for specific photothermal labeling and imaging of cancer cells. The QD PL
signal is retained in the cells post-treatment, thereby potentially enabling
persistent photothermal labeling of cancer cells for post-treatment cell tracking
and imaging-guided therapy evaluation.
PMID- 29938277
TI - Hierarchically porous composite microparticles from microfluidics for
controllable drug delivery.
AB - Abdominal wall defect repair remains a major clinical need, and a particle-based
controllable drug delivery system offers a solution to this problem. Here, we
present a new type of hierarchically porous microparticles (HPMs) composed of
poly(lactic-co-glycolic acid) (PLGA) and hollow mesoporous silica nanoparticles
(HMSNs) for the delivery. The HPMs are generated by drying microfluidic emulsion
templates of HMSNs-dispersed PLGA solution. The resultant HPMs have tailorable
porous structures, that provide a three-hierarchy architecture for the controlled
release of actives. The first hierarchy is formed for controlling the drug
release via physical absorption as a result of the presence of the HMSNs in the
HPMs. The second hierarchy channels with small pores scattered throughout the
surface of the HPMs are formed during evaporation of the solvent. The third
hierarchy with openings on the surface of the HPMs is formed as a result of the
inner droplets leaking out of the double emulsion templates during the PLGA
solidification. Thus, by manipulating the flow of solutions during the
microfluidic emulsification, the porous structures of HPMs can be easily and
precisely adjusted, and the loaded drugs are delivered at the required rate.
These features of the HPMs make them ideal for repairing abdominal wall defects.
PMID- 29938278
TI - A nanoporous sulfur-bridged hexaazatrinaphthylene framework as an organic cathode
for lithium ion batteries with well-balanced electrochemical performance.
AB - Some inherent drawbacks of organic cathode materials include low conductivity and
high solubility in electrolytes, which lead to low rate capability and low
cycling stability. Herein, a novel nanoporous sulfur-bridged
hexaazatrinaphthylene (NSHATN) framework has been developed. The sulfur-bridged
aromatic framework has good electrical conductivity and is insoluble in
electrolytes. The well-defined nanoporous structure with the pore size dominant
at 1.26 nm endows the framework with good ionic conductivity. With that, the
NSHATN cathode for lithium ion batteries gives well-balanced electrical
performances in capacity, cycling stability and rate capability.
PMID- 29938279
TI - Palladium catalyzed chloroethoxylation of aromatic and heteroaromatic chlorides:
an orthogonal functionalization of a chloroethoxy linker.
AB - A novel disconnection based on cross-coupling chemistry was designed to access
pharmaceutically relevant aryl-aminoethyl ethers. The developed palladium
catalyzed functionalization of aryl- and heteroaryl chlorides with a sodium
tetrakis-(2-chloroethoxy) borate salt is orthogonal to the simple nucleophilic
replacement of the chloro function of the ethylene linker. The transformation
enables efficient 2-chloroethoxylation in the absence of an additional external
base. Subsequent amine substitution of the alkyl halide affords 2-aminoethoxy
arenes. The applicability of this method was demonstrated through the synthesis
of various aryl- and heteroaryl-alkyl ethers, including the intermediates of
marketed drug molecules.
PMID- 29938280
TI - Multiplexed discrimination of microRNA single nucleotide variants through triplex
molecular beacon sensors.
AB - Herein, we develop a new nanopore sensing strategy for the selective detection of
microRNAs and single nucleotide variants (SNVs) based on triplex molecular beacon
sensors. This sensing system shows very high specificity in discriminating
microRNA SNVs and can be applied for the simultaneous detection of several
microRNAs of the same family in a mixture.
PMID- 29938281
TI - Auto-oxidation promoted sp3 C-H arylation of glycine derivatives.
AB - An auto-oxidation promoted sp3 C-H arylation reaction between N-aryl glycine
derivatives and electron-rich arenes, leading to the formation of N-aryl alpha
aryl alpha-amino acid derivatives, is described. This atom-economical and
environmentally benign reaction proceeds smoothly under mild reaction conditions
and requires only Bronsted acid and oxygen (balloon). A plausible radical
involved mechanism is proposed.
PMID- 29938282
TI - Misconceptions in electronic energy transfer: bridging the gap between chemistry
and physics.
AB - Many treatments of energy transfer (ET) phenomena in current literature employ
incorrect arguments and formulae and are not quantitative enough. This is
unfortunate because we witness important breakthroughs from ET experiments in
nanoscience. This review aims to clarify basic principles by focusing upon
Forster-Dexter electric dipole-electric dipole (ED-ED) ET. The roles of ET in
upconversion, downconversion and the antenna effect are described and the cliches
and simple formulae to be avoided in ET studies are highlighted with alternative
treatments provided.
PMID- 29938283
TI - Time-resolved FTIR study of light-driven sodium pump rhodopsins.
AB - Light-driven sodium ion pump rhodopsin (NaR) is a new functional class of
microbial rhodopsin. A previous flash photolysis study of Krokinobacter eikastus
rhodopsin 2 (KR2) revealed the presence of three kinetically distinct
intermediates: K, L/M, and O. Previous low-temperature Fourier-transform infrared
(FTIR) spectroscopy of KR2 showed that photoisomerization from the all-trans to
the 13-cis form is the primary event of the Na+ pumping photocycle, but
structural information on the subsequent intermediates is limited. Here, we
applied step-scan time-resolved FTIR spectroscopy to KR2 and Nonlabens
dokdonensis rhodopsin 2 (NdR2). Both low-temperature static and time-resolved
FTIR spectra resolved a K-like intermediate, and the corresponding spectra showed
few differences. Strong hydrogen-out-of-plane (HOOP) vibrations, which appeared
in the K intermediate, are common among other rhodopsins. It is, however, unique
for NaR that such HOOP bands are persistent in late intermediates, such as L and
O intermediates. This observation strongly suggests similar chromophore
structures for the K, L, and O intermediates. In fact, an isotope-labeled study
that used 12,14-D2 retinal revealed that the chromophore configuration of the O
intermediate in NaR is 13-cis. In contrast to the vibrations of the chromophore,
those of the protein differ among intermediates, and this is related to the
sodium-pumping function. The molecular mechanism of the light-driven sodium pump
is discussed on the basis of the present time-resolved FTIR results.
PMID- 29938284
TI - Ferromagnetic nanoparticle-embedded hybrid nanogenerator for harvesting
omnidirectional vibration energy.
AB - A new form of generator known as the triboelectric nanogenerator (TENG) has
recently been suggested as a simple and low-cost solution to scavenge ambient
mechanical energy. Although there have been substantial advances in TENGs over
the past few years, the power efficiency of TENGs must be enhanced further before
they can be practically applied. In the present study, we report a ferromagnetic
nanoparticle-embedded hybrid nanogenerator (FHNG) which operates based on both
triboelectricity and electromagnetic induction. A TENG and an electromagnetic
generator (EMG) efficiently cooperate to generate electrical energy from the same
motion, i.e., the vibration of a synthesized nanoparticle. A surface
functionalized ferric oxide nanoparticle, which has strong ferromagnetism and
high triboelectricity, was produced by a simple surface-coating process. The
measured electrical characteristics revealed that the output voltage of both the
TENG and the EMG components increased by approximately 50 times and by twofold,
respectively, after the surface functionalization step. Moreover, when constant
vibration of 3 Hz is applied to the fabricated FHNG, the TENG and EMG components
correspondingly generated output power of 133.2 MUW at a load resistance of 100
MOmega and 6.5 MUW at a load resistance of 200 Omega. The output power per unit
mass from the FHNG is greater than that according to the arithmetic sum of the
individual TENG and EMG components, demonstrating synergy between the two
components. Furthermore, the device can generate stable output under various
vibration directions, amplitudes, and frequencies due to the fluid-like
characteristics of the powder. The packaged structure also securely protects the
device from external humidity and dust. Connected to a rationally designed power
management circuit, a digital clock was turned on solely by the fabricated FHNG.
PMID- 29938285
TI - Multi-step phase-cycling in a free-electron laser-powered pulsed electron
paramagnetic resonance spectrometer.
AB - Electron paramagnetic resonance (EPR) is a powerful tool for research in
chemistry, biology, physics and materials science, which can benefit
significantly from moving to frequencies above 100 GHz. In pulsed EPR
spectrometers driven by powerful sub-THz oscillators, such as the free electron
laser (FEL)-powered EPR spectrometer at UCSB, control of the duration, power and
relative phases of the pulses in a sequence must be performed at the frequency
and power level of the oscillator. Here we report on the implementation of an all
quasioptical four-step phase cycling procedure carried out directly at the kW
power level of the 240 GHz pulses used in the FEL-powered EPR spectrometer. Phase
shifts are introduced by modifying the optical path length of a 240 GHz pulse
with precision-machined dielectric plates in a procedure we call phase cycling
with optomechanical phase shifters (POPS), while numerical receiver phase cycling
is implemented in post-processing. The POPS scheme was successfully used to
reduce experimental dead times, enabling pulsed EPR of fast-relaxing spin systems
such as gadolinium complexes at temperatures above 190 K. Coherence transfer
pathway selection with POPS was used to perform spin echo relaxation experiments
to measure the phase memory time of P1 centers in diamond in the presence of a
strong unwanted FID signal in the background. The large excitation bandwidth of
FEL-EPR, together with phase cycling, enabled the quantitative measurement of
instantaneous electron spectral diffusion, from which the P1 center concentration
was estimated to within 10%. Finally, phase cycling enabled saturation-recovery
measurements of T1 in a trityl-water solution at room temperature - the first FEL
EPR measurement of electron T1.
PMID- 29938286
TI - Magnetic field effects in nematic and smectic liquid crystals probed by time
resolved observation of orientation relaxation of the spin probe.
AB - The kinetics of reorientation of the liquid crystal HOPOOB in nematic and smectic
phases in the magnetic field was studied by the spin probe technique. The time
evolution of the EPR spectrum shape in the course of reorientation in the nematic
phase indicates that the mechanism of alignment comprises redistribution between
domains of different orientations rather than the turn of the orientation
distribution function. A microscopic model of domain structure rearrangement is
provided to qualitatively describe the experimental data. In the smectic C phase,
partial reorientation is observed upon the action of the magnetic field. A
possible mechanism of this process is the reorientation of tilt direction within
the smectic layers. It is shown that this process is constrained, and the value
of the corresponding elastic constant is estimated.
PMID- 29938287
TI - Dehydration-triggered shape morphing based on asymmetric bubble hydrogel
microfibers.
AB - Inspired by nature, scientists have been engaged in developing deformable
artificial systems. Here, we propose an innovative method to realize controllable
deformations using asymmetric bubble hydrogel microfibers produced by
microfluidic cascaded coaxial devices. Asymmetric geometries, coupled with the
mismatched shrinkage ratio, contribute to deformations upon dehydration. The
dynamic process can be controlled by regulating bubble sizes, distances and
packing modes. Various 4D structures have been constructed. Combined with the 3D
printing technique, this proof-of-concept study may open new avenues for bio
engineering and beyond.
PMID- 29938288
TI - Bright, stable, and tunable solid-state luminescence of carbon nanodot
organogels.
AB - Despite the sustained enthusiastic interest in fluorescent carbon nanodots
(FCNDs), it is still challenging to achieve bright and widely tunable solid-state
luminescence. Herein, organogels embedded with FCNDs were simply synthesized via
a one-pot pyrolysis method. Subsequently, the excitation of a single ultraviolet
(UV) excitation line results in tunable solid-state luminescence ranging from
blue to red with quantum yields (QYs) >14%. In this study, N and S elements were
co-doped to regulate the aggregation of FCNDs, which consequently modulated the
Stokes shift of the photoluminescence (PL) by managing the degree of photon
reabsorption. Notably, without compact aggregations, the dispersions of FCNDs in
the organogel matrix indeed render bright fluorescence, which results from the
suppression of excessive photon reabsorption and nonradiative resonant energy
transfer (NRET).
PMID- 29938289
TI - Steric vs. electronic stereocontrol in syndio- or iso-selective ROP of functional
chiral beta-lactones mediated by achiral yttrium-bisphenolate complexes.
AB - Origins of stereoselectivity in ROP of racemic chiral cyclic esters promoted by
achiral yttrium complexes, resulting in the formation of highly heterotactic
polylactide, and highly syndiotactic or, more uniquely, highly isotactic poly(3
hydroxybutyrate)s, are discussed. A close interplay between the nature of the
cyclic ester, most particularly of the exocyclic functional chain installed on
the chiral center of beta-lactones, and the ortho-substituents installed on the
phenolate rings of the ligand, results in various determining secondary
interactions of steric and also electronic nature.
PMID- 29938290
TI - Hydrodynamics of shape-driven rigidity transitions in motile tissues.
AB - In biological tissues, it is now well-understood that mechanical cues are a
powerful mechanism for pattern regulation. While much work has focused on
interactions between cells and external substrates, recent experiments suggest
that cell polarization and motility might be governed by the internal shear
stiffness of nearby tissue, deemed "plithotaxis". Meanwhile, other work has
demonstrated that there is a direct relationship between cell shapes and tissue
shear modulus in confluent tissues. Joining these two ideas, we develop a
hydrodynamic model that couples cell shape, and therefore tissue stiffness, to
cell motility and polarization. Using linear stability analysis and numerical
simulations, we find that tissue behavior can be tuned between largely
homogeneous states and patterned states such as asters, controlled by a composite
"morphotaxis" parameter that encapsulates the nature of the coupling between
shape and polarization. The control parameter is in principle experimentally
accessible, and depends both on whether a cell tends to move in the direction of
lower or higher shear modulus, and whether sinks or sources of polarization tend
to fluidize the system.
PMID- 29938291
TI - Correction: Synthesis and spectroscopic characterization of group 4 post
metallocenes bearing (sigma-aryl)-2-phenolate-6-pyridyl and -isoquinolinyl
auxiliaries.
AB - Correction for 'Synthesis and spectroscopic characterization of group 4 post
metallocenes bearing (sigma-aryl)-2-phenolate-6-pyridyl and -isoquinolinyl
auxiliaries' by Jerry C. Y. Lo et al., Dalton Trans., 2015, 44, 15905-15913.
PMID- 29938292
TI - Temperature-dependent insertion and adsorption of lithium on spinel
Li4Ti5O12(111) thin films - an angle-resolved XPS study.
AB - Aiming at a detailed understanding of the Li adsorption and insertion behavior
on/into lithium titanate (Li4Ti5O12, LTO), which is a promising anode material in
Li-ion batteries, we have investigated the interaction of vapor deposited Li with
LTO in the temperature range between 80 K and room temperature by angle-resolved
X-ray photoelectron spectroscopy (ARXPS). The experiments were performed under
ultrahigh vacuum (UHV) conditions, and the presence of additional Li species was
detected by the formation of Ti3+ in the Ti 2p core level signal due to charge
transfer from adsorbed/inserted Li to Ti. Even at 80 K most of the deposited Li
diffuses into the bulk of LTO, reflecting the facile insertion and diffusion of
Li into and in LTO. Deposition of up to 3 monolayers equivalent (MLE) of Li at 80
K results in an increase in Li concentration in the surface region (topmost 6
nm), up to a stoichiometry of Li4+xTi5O12 with x > 0.3, and slightly lower values
in the near-surface region (topmost 1 nm). For higher Li doses, the amount of Li
in the near-surface region, including adsorbed Li, increases more than the
concentration in the underlying surface region. This is attributed to the
blocking of diffusion channels by inserted Li at a stoichiometry of Li4.3Ti5O12
and above. Upon increasing the temperature, Li+ starts to diffuse into the LTO
bulk at temperatures between 120 K and 175 K, depending on the concentration in
the surface region. It has completely disappeared at 260 K. The consequences of
these results for the understanding of physical Li insertion will be discussed.
PMID- 29938293
TI - Hexacene generated on passivated silicon.
AB - On-surface synthesis represents a successful strategy to obtain designed
molecular structures on an ultra-clean metal substrate. While metal surfaces are
known to favor adsorption, diffusion, and chemical bonding between molecular
groups, on-surface synthesis on non-metallic substrates would allow the
electrical decoupling of the resulting molecule from the surface, favoring
application to electronics and spintronics. Here, we demonstrate the on-surface
generation of hexacene by surface-assisted reduction on a H-passivated Si(001)
surface. The reaction, observed by scanning tunneling microscopy and
spectroscopy, is probably driven by the formation of Si-O complexes at dangling
bond defects. Supported by density functional theory calculations, we investigate
the interaction of hexacene with the passivated silicon surface, and with single
silicon dangling bonds.
PMID- 29938294
TI - Frustrated Lewis pairs in ionic liquids and molecular solvents - a neutron
scattering and NMR study of encounter complexes.
AB - The presence of the weakly-associated encounter complex in the model frustrated
Lewis pair solution (FLP): tris(tert-butyl)phosphine (P(tBu)3) and
tris(pentafluorophenyl)borane (BCF) in benzene, was confirmed via PB correlation
analysis from neutron scattering data. On average, ca. 5% of dissolved FLP
components were in the associated state. NMR spectra of the FLP in benzene gave
no evidence of such association, in agreement with earlier reports and the
transient nature of the encounter complex. In contrast, the corresponding FLP
solution in the ionic liquid, 1-decyl-3-methylimidazolium bistriflamide,
[C10mim][NTf2], generated NMR signals that can be attributed to formation of
encounter complexes involving over 20% of the dissolved species. The low
diffusivity characteristics of ionic liquids is suggested to enhance high
populations of encounter complex. The FLP in the ionic liquid solution retained
its ability to split hydrogen.
PMID- 29938295
TI - Bifunctional mannoside-glucosinolate glycoconjugates as enzymatically triggered
isothiocyanates and FimH ligands.
AB - Glucosinolates are sulfur-containing secondary metabolites found in plants of the
Brassicale order. They are precursors of isothiocyanate species, resulting from C
S hydrolysis catalysed by the thioglucohydrolase myrosinase. We describe the
synthesis of bifunctional glucosinolate-mannoside glycoconjugates combining both
the structural features of a substrate of myrosinase and a ligand of the lectin
FimH. We show that these glycoconjugates serve as enzyme substrates and that
myrosinase can indeed hydrolyze the glucosinolate moiety with affinities (KM,
Vmax) comparable to the natural substrates glucomoringin and sinigrin. This
enzymatic hydrolysis of the thioglycosidic bond led to the efficient formation of
an isothiocyanate which was assessed by the formation of the corresponding
dithiocarbamate derivatives. Finally, we show that our synthetic bifunctional
glycoconjugates also serve as FimH ligands where the glucosinolate moiety does
not hamper the interaction with the lectin. Our findings set the stage for an
original bioconjugation tool, allowing for myrosinase-triggered specific
labelling of lectins using glucosinolate glycoconjugates as non-toxic, water
soluble isothiocyanate precursors.
PMID- 29938296
TI - Mobility trends of psychiatric trainees in Turkey: hard to leave, harder to stay?
PMID- 29938298
TI - Bridging the Gap in Global Advanced Radiation Oncology Training: Impact of a Web
Based Open-Access Interactive Three-Dimensional Contouring Atlas on Radiation
Oncologist Practice in Russia.
AB - Radiation oncologists in Russia face a number of unique professional difficulties
including lack of standardized training and continuing medical education. To
combat this, under the auspices of the Russian Society of Clinical Oncology
(RUSSCO), our group has developed a series of ongoing in-person interactive
contouring workshops that are held during the major Russian oncology conferences
in Moscow, Russia. Since November 2016 during each workshop, we utilized a web
based open-access interactive three-dimensional contouring atlas as part of our
didactics. We sought to determine the impact of this resource on radiation
oncology practice in Russia. We distributed an IRB-approved web-based survey to
172 practicing radiation oncologists in Russia. We inquired about practice
demographics, RUSSCO contouring workshop attendance, and the clinical use of open
access English language interactive contouring atlas (eContour). The survey
remained open for 2 months until November 2017. Eighty radiation oncologists
completed the survey with a 46.5% response rate. Mean number of years in practice
was 13.7. Sixty respondents (75%) attended at least one RUSSCO contouring
workshop. Of those who were aware of eContour, 76% were introduced during a
RUSSCO contouring workshop, and 81% continue to use it in their daily practice.
The greatest obstacles to using the program were language barrier (51%) and
internet access (38%). Nearly 90% reported their contouring practices changed
since they started using the program, particularly for delineation of clinical
target volumes (57%) and/or organs at risk (46%). More than 97% found the
clinical pearls/links to cooperative group protocols in the software helpful in
their daily practice. The majority used the contouring program several times per
month (43%) or several times per week (41%). Face-to-face contouring instruction
in combination with open-access web-based interactive contouring resource had a
meaningful impact on perceived quality of radiation oncology contours among
Russian practitioners and has the potential to have applications worldwide.
PMID- 29938297
TI - Role of osteopontin in bone remodeling and orthodontic tooth movement: a review.
AB - In this review, most of the known and postulated mechanisms of osteopontin (OPN)
and its role in bone remodeling and orthodontic tooth movement are discussed
based on available literature. OPN, a multifunctional protein, is considered
crucial for bone remodeling, biomineralization, and periodontal remodeling during
mechanical tension and stress (orthodontic tooth movement). It contributes to
bone remodeling by promoting osteoclastogenesis and osteoclast activity through
CD44- and alphavbeta3-mediated cell signaling. Further, it has a definitive role
in bone remodeling by the formation of podosomes, osteoclast survival, and
osteoclast motility. OPN has been shown to have a regulatory effect on
hydroxyapatite crystal (HAP) growth and potently inhibits the mineralization of
osteoblast cultures in a phosphate-dependent manner. Bone remodeling is vital for
orthodontic tooth movement. Significant compressive and tensional forces on the
periodontium induce the signaling pathways mediated by various osteogenic genes
including OPN, bone sialoprotein, Osterix, and osteocalcin. The signaling
pathways involved in the regulation of OPN and its effect on the periodontal
tissues during orthodontic tooth movement are further discussed in this review. A
limited number of studies have suggested the use of OPN as a biomarker to assess
orthodontic treatment. Furthermore, the association of single nucleotide
polymorphisms (SNPs) in OPN coding gene Spp1 with orthodontically induced root
resorption remains largely unexplored. Accordingly, future research directions
for OPN are outlined in this review.
PMID- 29938299
TI - Electroporation of germinated conidia and young mycelium as an efficient
transformation system for Acremonium chrysogenum.
AB - Three different transformation strategies were tested and compared in an attempt
to facilitate and improve the genetic transformation of Acremonium chrysogenum,
the exclusive producer of the pharmaceutically relevant beta-lactam antibiotic
cephalosporin C. We investigated the use of high-voltage electric pulse to
transform germinated conidia and young mycelium and compared these procedures
with traditional PEG-mediated protoplast transformation, using phleomycin
resistance as selection marker in all cases. The effect of the field strength and
capacitance on transformation frequency and cell viability was evaluated. The
electroporation of germinated conidia and young mycelium was found to be
appropriate for transforming A. chrysogenum with higher transformation
efficiencies than those obtained with the conventional protoplast-based
transformation procedures. The developed electroporation strategy is fast, simple
to perform, and highly reproducible and avoids the use of chemicals toxic to
cells. Electroporation of young mycelium represents an alternative method for
transformation of fungal strains with reduced or no sporulation, as often occurs
in laboratory-developed strains in the search for high-yielding mutants for
industrial bioprocesses.
PMID- 29938302
TI - Enhancement of low-quality fetal electrocardiogram based on time-sequenced
adaptive filtering.
AB - Extraction of a clean fetal electrocardiogram (ECG) from non-invasive abdominal
recordings is one of the biggest challenges in fetal monitoring. An ECG allows
for the interpretation of the electrical heart activity beyond the heart rate and
heart rate variability. However, the low signal quality of the fetal ECG hinders
the morphological analysis of its waveform in clinical practice. The time
sequenced adaptive filter has been proposed for performing optimal time-varying
filtering of non-stationary signals having a recurring statistical character. In
our study, the time-sequenced adaptive filter is applied to enhance the quality
of multichannel fetal ECG after the maternal ECG is removed. To improve the
performance of the filter in cases of low signal-to-noise ratio (SNR), we enhance
the ECG reference signals by averaging consecutive ECG complexes. The performance
of the proposed augmented time-sequenced adaptive filter is evaluated in both
synthetic and real data from PhysioNet. This evaluation shows that the suggested
algorithm clearly outperforms other ECG enhancement methods, in terms of
uncovering the ECG waveform, even in cases with very low SNR. With the presented
method, quality of the fetal ECG morphology can be enhanced to the extent that
the ECG might be fit for use in clinical diagnostics. Graphical abstract The
extracted fetal ECG signals from non-invasive abdominal recordings still contain
a substantial amount of noise. The time-sequenced adaptive filter provides a
relatively accurate estimate of the underlying fetal ECG signal when the quality
of the reference channels is enhanced prior to filtering.
PMID- 29938301
TI - Dynamics of tissue ingrowth in SIKVAV-modified highly superporous PHEMA scaffolds
with oriented pores after bridging a spinal cord transection.
AB - While many types of biomaterials have been evaluated in experimental spinal cord
injury (SCI) research, little is known about the time-related dynamics of the
tissue infiltration of these scaffolds. We analyzed the ingrowth of connective
tissue, axons and blood vessels inside the superporous poly (2-hydroxyethyl
methacrylate) hydrogel with oriented pores. The hydrogels, either plain or seeded
with mesenchymal stem cells (MSCs), were implanted in spinal cord transection at
the level of Th8. The animals were sacrificed at days 2, 7, 14, 28, 49 and 6
months after SCI and histologically evaluated. We found that within the first
week, the hydrogels were already infiltrated with connective tissue and blood
vessels, which remained stable for the next 6 weeks. Axons slowly and gradually
infiltrated the hydrogel within the first month, after which the numbers became
stable. Six months after SCI we observed rare axons crossing the hydrogel bridge
and infiltrating the caudal stump. There was no difference in the tissue
infiltration between the plain hydrogels and those seeded with MSCs. We conclude
that while connective tissue and blood vessels quickly infiltrate the scaffold
within the first week, axons show a rather gradual infiltration over the first
month, and this is not facilitated by the presence of MSCs inside the hydrogel
pores. Further research which is focused on the permissive micro-environment of
the hydrogel scaffold is needed, to promote continuous and long-lasting tissue
regeneration across the spinal cord lesion.
PMID- 29938303
TI - Intramedullary cervical abscess mimicking a spinal cord tumor in a 10-year-old
girl: a case-based review.
AB - BACKGROUND: Intramedullary spinal cord abscesses (ISCA) are a rare pathological
entity with very few cases reported in the world and may be confused with an
intramedullary tumor. Cervical location is the least frequently affected, except
for cryptogenic spread, mostly seen in adult patients. Meticulous study of
contrast-enhanced MRI pictures has a key role in the diagnosis. METHOD AND
RESULTS: We present a case of a spontaneous cervical ISCA, mimicking a spinal
cord tumor, in a pediatric patient with good outcome. A review of the literature
shows that this is a life-threatening condition with high chances of rupture and
subsequent meningitis. CONCLUSIONS: We point out that if a solitary cervical
spinal cord lesion is surrounded by significant medullar edema associated with
fast onset of symptoms, fever, and elevation of WBC, the possibility of a spinal
cord abscess should be considered prior to surgery.
PMID- 29938300
TI - Guidelines on nuclear medicine imaging in neuroblastoma.
AB - Nuclear medicine has a central role in the diagnosis, staging, response
assessment and long-term follow-up of neuroblastoma, the most common solid
extracranial tumour in children. These EANM guidelines include updated
information on 123I-mIBG, the most common study in nuclear medicine for the
evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and
68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical
practice. Indications, advantages and limitations are presented along with
recommendations on study protocols, interpretation of findings and reporting
results.
PMID- 29938304
TI - Outcomes in children with central nervous system tumors disseminated at
presentation: a large single-center experience.
AB - PURPOSE: Children with disseminated central nervous system (CNS) tumors have
worse outcomes than those with solitary disease, but outcomes of disease
dissemination at initial presentation have not been systematically studied and
compared across tumor groups to date. We evaluated the impact of tumor
dissemination at presentation on management and clinical outcomes in a cohort of
consecutively treated children in a single neurosurgical unit over a 14-year
period. METHODS: Method used was a retrospective review of data on children
presenting to Great Ormond Street Hospital, London, UK, with medulloblastoma,
primitive neuroectodermal tumor, atypical teratoid rhabdoid tumor, pilocytic
astrocytoma, and ependymoma between 2003 and 2016 inclusive. Uni- and multi
variate analyses were performed to evaluate a range of outcome measures. RESULTS:
Three-hundred sixty-one children were identified in total, 53 with disease
dissemination at presentation (M:F = 34:19, median age = 3.8 years, range = 7
days-15.6 years) and 308 with solitary tumors (M:F = 161:147, median age = 5.8
years, range = 1 day-16.9 years). Median follow-up was similar irrespective of
dissemination status (disseminated tumor 64.0 months, range = 5.2-152.0 months;
solitary tumor 74.5 months, range = 4.7-170.1 months; P > 0.05). In multivariate
analyses, tumor type and dissemination status at presentation were significantly
associated with overall survival (P < 0.0001), risk of recurrence/disease
progression (P < 0.01), and event-free survival (P < 0.0001). Subtotal resection
was associated with shorter time to recurrence/disease progression (P < 0.01) and
worse event-free (P < 0.0001) but not overall survival, whereas treatment with
chemotherapy and radiotherapy were associated with improved overall (Ps < 0.0001)
and event-free survival (Ps < 0.05). Differences between tumor groups were
evident. CONCLUSIONS: Dissemination status at initial presentation significantly
affects outcomes in children with CNS tumors.
PMID- 29938306
TI - What occurs in the other 20% of cancer patients with chemotherapy-induced nausea
and vomiting (CINV)? A single-institution qualitative study.
AB - PURPOSE: Despite recent advances in prophylaxis and management, 20% of patients
who receive moderately to severely emetogenic chemotherapy continue to experience
nausea and vomiting. Relying on patients' own words, this study sought to capture
and characterize the lived experience with chemotherapy-induced nausea and
vomiting (CINV) for this important subgroup of patients. METHODS: Solid tumor
patients with a history of poorly controlled CINV provided informed consent and
participated in a semi-structured interview, which was audio-recorded and
transcribed. After data saturation, enrollment ceased, and inductive, qualitative
analytic methods were employed. RESULTS: The median age of the 20 enrolled
patients was 56 years (range 27-83) with an equal gender split; half had
gastrointestinal cancers. Two themes emerged. First, CINV is severe and
multidimensional: "It's like shredding your muscles... It's doing it over and
over again." This symptom complex has psychosocial implications: "Isolation is a
big thing." Financial toxicity is also implicated: "I use [an antiemetic] when I
feel like it is absolutely necessary because it is so expensive I cannot afford
it anyway." The second theme is underreporting of symptoms. Patients seemed to
accept N/V as part of treatment and were therefore less forthcoming: "God, if
you're pumping poison in your system, you gotta expect some side effects."
CONCLUSIONS: These vivid data should motivate investigators to continue
conducting clinical trials CINV and should remind healthcare providers about the
importance of patient education on the availability of therapy for breakthrough
symptomatology.
PMID- 29938305
TI - Characterization of methanthelinium binding and function at human M1-M5
muscarinic acetylcholine receptors.
AB - Firstly, it was determined whether methanthelinium bromide (MB) binds to human M1
M5 (hM1-hM5) muscarinic acetylcholine receptors in comparison to the classical
muscarinic antagonist N-methylscopolamine (NMS). [3H]NMS dissociation binding
experiments revealed an allosteric retardation of dissociation at 100 MUM of MB
ranging from none in hM3 to 4.6-fold in hM2 receptors. Accordingly, global non
linear regression analysis of equilibrium inhibition binding curves between
[3H]NMS (0.2 and 2.0 nM) and MB was applied and compared using either an
allosteric or a competitive model. The allosteric cooperativity of MB binding
within MB/NMS/hM receptor complexes was strongly negative and undistinguishable
from a competitive interaction throughout all subtypes. Applying the competitive
model to the equilibrium binding data of MB and NMS, suggested competition at all
hM subtypes: logKI (+/- S.E.) hM3 = 8.71 +/- 0.15, hM1 = 8.68 +/- 0.14, hM5 =
8.58 +/- 0.07, hM2 = 8.27 +/- 0.07 to hM4 = 8.25 +/- 0.11. Secondly, the effects
of MB on acetylcholine (ACh) induced hM receptor function showed very strong
negative allosteric cooperativity at all subtypes pointing against an allosteric
antagonism of MB with ACh. Competition with ACh was characterized by logKB: hM1 =
9.53 +/- 0.05, hM4 = 9.33 +/- 0.05, hM5 = 8.80 +/- 0.05, hM2 = 8,79 +/- 0.06, to
hM3 = 8.43 +/- 0.04. In conclusion, MB, below 1 MUM, binds competitively and non
selectively (except for the difference between hM3 vs. hM4) to all five hM
receptor subtypes with nanomolar affinity and is able to functionally inhibit ACh
responses in a competitive fashion, with a slight subtype preference for hM1 and
hM4.
PMID- 29938307
TI - Correction to: The ESSKA-AFAS international consensus statement on peroneal
tendon pathologies.
AB - Unfortunately, the spelling of the names Daniel Haverkamp and Akos Kynsburg were
incorrect in the original online publication of the article.
PMID- 29938308
TI - Sleep Apnea Is a Risk Factor for Stroke and Vascular Dementia.
AB - PURPOSE OF REVIEW: In this article, we review the cerebrovascular complications
of sleep apnea (SA). SA is the major sleep disorder associated with stroke and
vascular dementia. RECENT FINDINGS: Sleep apnea syndrome of moderate to severe
intensity affects 17% of 50-70-year-old men and 9% of 50-70-year-old women,
making SA a notorious and prevalent disorder. SA increases the risk of
hypertension, stroke, myocardial infarction, and atrial fibrillation (AF) and is
closely linked to vascular dementia. In addition, SA may worsen the neurologic
outcome in acute stroke patients and interferes with rehabilitation after stroke.
Proper management of SA may decrease the clinical impact of stroke risk factors,
improve neurologic outcome after stroke, and lessen the progression of
subcortical ischemic vascular disease. In this article, we will cover the most
salient pathologies that associate SA and cerebrovascular pathology.
PMID- 29938309
TI - Low frequency of CD3+CD4+CD161+ T cells correlates with the occurrence of
infections in refractory/relapsed multiple myeloma patients receiving
lenalidomide plus low-dose dexamethasone treatment.
AB - The aim of this study was to explore the predictive implications of the
composition of immune cell populations prior to lenalidomide plus high-dose
dexamethasone (Len-Dex) initiation for the occurrence of infections. We
prospectively examined immune cell populations in peripheral blood taken at
baseline of lenalidomide plus low-dose dexamethasone (Len-dex) therapy and
reviewed clinical and microbiology records in 90 patients with
refractory/relapsed multiple myeloma (RRMM). Risk factors for infection were
analyzed using logistic regression. During a median of 11 cycles of Len-dex
treatment, 52 (57.8%) patients experienced at least 1 infection episode. Of a
total of 92 episodes of infection, 58 (63%) episodes were clinically defined, 29
(31.5%) episodes were microbiologically defined, and 5 (5.4%) episodes were fever
of unknown origin. Severe episodes were more frequently observed during the first
3 cycles. After adjusting for risk factors for infection based on univariate
analyses, multivariate analyses showed that lower Hb (< 10 g/dL) was a clinically
independent factor associated with occurrence of infections. Lower frequency (P =
0.044) and absolute count (P = 0.014) of circulating CD3+CD4+CD161+ cells prior
to Len-dex treatment were also associated with the occurrence of infection,
especially during the first 3 cycles of Len-dex therapy. In addition to several
clinical predictive factors, we found that CD3+CD4+CD161+ cells may provide
additional information for predicting the occurrence of infection in the early
period of Len-dex therapy.
PMID- 29938310
TI - Functional cargo delivery into mouse and human fibroblasts using a versatile
microfluidic device.
AB - Efficient intracellular cargo delivery is a key hurdle for the translation of
many emerging stem cell and cellular reprogramming therapies. Recently, a
microfluidic-based device constructed from silicon was shown to transduce
macromolecules into cells via shear-induced formation of plasma membrane pores.
However, the scalability and widespread application of the current platform is
limited since physical deformation-mediated delivery must be optimized for each
therapeutic application. Therefore, we sought to create a low-cost, versatile
device that could facilitate rapid prototyping and application-specific
optimization in most academic research labs. Here we describe the design and
implementation of a microfluidic device constructed from Polydimethylsiloxane
(PDMS) that we call Cyto-PDMS (Cytoplasmic PDMS-based Delivery and Modification
System). Using a systematic Cyto-PDMS workflow, we demonstrate intracellular
cargo delivery with minimal effects on cellular viability. We identify specific
flow rates at which a wide range of cargo sizes (1-70 kDa) can be delivered to
the cell interior. As a proof-of-principle for the biological utility of Cyto
PDMS, we show (i) F-actin labeling in live human fibroblasts and (ii)
intracellular delivery of recombinant Cre protein with appropriate genomic
recombination in recipient fibroblasts. Taken together, our results demonstrate
that Cyto-PDMS can deliver small-molecules to the cytoplasm and biologically
active cargo to the nucleus without major effects on viability. We anticipate
that the cost and versatility of PDMS can be leveraged to optimize delivery to a
broad array of possible cell types and thus expand the potential impact of
cellular therapies.
PMID- 29938311
TI - Molecular dynamics simulations of a DMSO/water mixture using the AMBER force
field.
AB - Due to its protective properties of biological samples at low temperatures and
under desiccation, dimethyl sulfoxide (DMSO) in aqueous solutions has been
studied widely by many experimental approaches and molecular dynamics (MD)
simulations. In the case of the latter, AMBER is among the most commonly used
force fields for simulations of biomolecular systems; however, the parameters for
DMSO published by Fox and Kollman in 1998 have only been tested for pure liquid
DMSO. We have conducted an MD simulation study of DMSO in a water mixture and
computed several structural and dynamical properties such as of the mean density,
self-diffusion coefficient, hydrogen bonding and DMSO and water ordering. The
AMBER force field of DMSO is seen to reproduce well most of the experimental
properties of DMSO in water, with the mixture displaying strong and specific
water ordering, as observed in experiments and multiple other MD simulations with
other non-polarizable force fields. Graphical abstract Hydration structure within
hydrogen-bonding distance around a DMSOmolecule.
PMID- 29938312
TI - Prevalence and topographical characteristics of keratoconus in patients with
refractive errors in the Egyptian delta.
AB - PURPOSE: To study the prevalence of keratoconus (KC) and the topographical
characteristics of the affected corneas in patients with refractive errors who
were seeking refractive surgery in the Egyptian delta. METHODS: A retrospective
study covering four and half years (Jan 2012-June 2016) where the topographical
data of 8124 participants were obtained from the records of a refractive center
in the Nile delta region, Egypt. The diagnosis of KC was based on the Holladay
criteria in one or both eyes, using the Pentacam scans, whereas grading of KC was
based on the Amsler-Krumeich classification. RESULTS: The prevalence of KC was
1.12% (91/8124 participants) with 95% confidence interval 0.91-1.3. Of all the
affected cases, 5 cases (5.5%) had unilateral, and the other 86 cases (94.5%) had
bilateral KC. The affected and unaffected subjects did not show any significant
difference regarding gender. Sixty-eight (38.4%) eyes had stage 1 KC, 53 eyes
(29.9%) had stage 2, 27 eyes (15.3%) had stage 3, and 29 eyes (16.4%) had stage 4
KC. It was most prevalent (1.2%) among cases with astigmatism (P < 0.001).
CONCLUSION: Keratoconus was found in 1.12% of patients seeking refractive
surgery, with no gender preference. Most cases had bilateral affection.
Astigmatism was the most common refractive error to be associated with
keratoconus.
PMID- 29938313
TI - The Effect of BSA-Based Curcumin Nanoparticles on Memory and Hippocampal MMP-2,
MMP-9, and MAPKs in Adult Mice.
AB - Although high rate of curcumin consumption has been suggested to decrease the
prevalence of Alzheimer's disease (AD), its administration has no effect on the
progression of AD in humans and this has been attributed to its poor
bioavailability. Using nanotechnology to break down curcumin increases its
bioavailability and improves its effect on the brain. BSA, as a non-toxic protein
with high binding capacity, was used to break curcumin to nanosize and to explore
the effect of nanocurcumin on passive avoidance memory and hippocampal MMP-2 and
9 and MAPKs. BSA-based nanocurcumin was produced by desolvation method. In this
study, 15 and 20 mg/kg/p.o. nanocurcumin (based on our preliminary studies) were
administered to male NMRI mice weighing 20-25 g for 10 days. Passive avoidance
training was performed on day 10 and 24 h after, a retention trial was done. Upon
completion of behavioral studies, the hippocampi were isolated and western blot
analysis was performed on MMP-2, MMP-9, and MAPKs (JNK, ERK, and p38). The
results showed that BSA-based nanocurcumin administered at 15 and 20 mg/kg doses
resulted in a significantly improved performance in passive avoidance memory test
while its equivalent doses of natural curcumin did not produce a similar effect.
In addition, this effect was accompanied with an increase in MMP-2, MMP-9, and p
ERK and a decrease in p-JNK. This study indicates that breaking curcumin to
nanosize produces improved effects on passive avoidance memory in adult mice
accompanied with MMP-2, MMP-9, p-ERK, and p-JNK changes in the hippocampus.
PMID- 29938314
TI - Role of poly(ethylene oxide) in copper-containing composite used for intrauterine
contraceptive devices.
AB - Copper-containing composite is a cupric ions release system to prepare a novel
copper intrauterine devices (Cu-IUDs), its biocompatibility and weight of the
prepared composite Cu-IUDs are directly relevant to its such side-effects as pain
and bleeding. To improve its biocompatibility and reduce its weight of such a
composite Cu-IUDs, a copper-containing composite based on polymer alloy of
poly(ethylene oxide) (PEO) and low-density polyethylene (LDPE) is developed. Here
the role of its PEO in this novel cupric ions release system is reported. The
results show that its cupric ions release rate can be adjusted easily by only
changing its PEO content, and it increases remarkably with the increase of its
PEO content. Our study also show that this influence is caused by the improvement
of its hydrophilicity and the formation of its porous structure owing to the
introduction of PEO. The improvement of its hydrophilicity make it easier for the
surrounding aqueous solution to infiltrate into the composite, and the formation
of its porous structure provide more routes for entry of the aqueous solution and
diffusion of the released cupric ions. All these results indicate that the
Cu/PEO/LDPE composite is a potential material that can be used to prepare such
cupric ions release micro-devices as Cu-IUDs with slighter side-effects through
its smaller weight.
PMID- 29938315
TI - Comparison of photosynthetic performances of marine picocyanobacteria with
different configurations of the oxygen-evolving complex.
AB - The extrinsic PsbU and PsbV proteins are known to play a critical role in
stabilizing the Mn4CaO5 cluster of the PSII oxygen-evolving complex (OEC).
However, most isolates of the marine cyanobacterium Prochlorococcus naturally
miss these proteins, even though they have kept the main OEC protein, PsbO. A
structural homology model of the PSII of such a natural deletion mutant strain
(P. marinus MED4) did not reveal any obvious compensation mechanism for this
lack. To assess the physiological consequences of this unusual OEC, we compared
oxygen evolution between Prochlorococcus strains missing psbU and psbV (PCC 9511
and SS120) and two marine strains possessing these genes (Prochlorococcus sp.
MIT9313 and Synechococcus sp. WH7803). While the low light-adapted strain SS120
exhibited the lowest maximal O2 evolution rates (Pmax per divinyl-chlorophyll a,
per cell or per photosystem II) of all four strains, the high light-adapted
strain PCC 9511 displayed even higher PChlmax and PPSIImax at high irradiance
than Synechococcus sp. WH7803. Furthermore, thermoluminescence glow curves did
not show any alteration in the B-band shape or peak position that could be
related to the lack of these extrinsic proteins. This suggests an efficient
functional adaptation of the OEC in these natural deletion mutants, in which PsbO
alone is seemingly sufficient to ensure proper oxygen evolution. Our study also
showed that Prochlorococcus strains exhibit negative net O2 evolution rates at
the low irradiances encountered in minimum oxygen zones, possibly explaining the
very low O2 concentrations measured in these environments, where Prochlorococcus
is the dominant oxyphototroph.
PMID- 29938316
TI - A high-fat diet induced NMRI mouse model of metabolic syndrome: focus on brain
derived neurotrophic factor (BDNF).
AB - The association of brain-derived neurotrophic factor (BDNF) as a member of
neurotrophin family and metabolic syndrome (MetS) has been proposed, however
basic evidence necessary to prove (or disprove) this association in non-genetic
animal model is rare. Therefore, we investigated the alteration of encephalic
BDNF gene expression in a mouse model of high-fat diet (HFD) induced MetS. To
translate MetS, male NMRI mice (9 weeks old; N = 13) fed on a HFD including suet
powder (37.50%) and granulated sugar (19.85%) while control mice were fed a diet
contained suet powder (6.25%) and granulated sugar (49.09%). We monitored the
development of MetS by measuring fasting blood sugar (FBS) and lipid (total
cholesterol (TC) and triacylglycerol (TGs)) and lipoprotein (high-density
lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL
C)) profiles, atherogenic index (AI), and somatic indices after 1 and 3 months of
dietary interventions. The HFD intake led to increased body weight, liver weight,
FBS, TC, and decreased HDL-C as compared to chow diet in mice after first month
of dietary intervention. The increased FBS, body weight, abdominal fat mass, TGs,
TC, and VLDL-C and decreased HDL-C were observed in HFD-fed mice as compared to
those of chow-fed mice at 3th month. The statistical comparison of two HFD groups
in two time intervals of 1st and 3th month confirmed that our HFD-induced MetS
model was reliable because FBS, TGs and VLDL-C, TC, and AI have been increased
significantly during selected time intervals. The AI increased significantly in
HFD-fed mice compared to chow-fed mice after 3 months. The AI in HFD-fed mice
treated with HFD for 3 months was increased significantly as compared to mice fed
HFD for 1 month. Our diet-induced model more closely mimics the changes observed
in human MetS and showed that encephalic BDNF gene in mice fed HFD was under
expressed by 0.30 fold with respect to chow-fed mice after 3 months of dietary
intervention.
PMID- 29938317
TI - Identification and metabolomic analysis of chemical elicitors for tacrolimus
accumulation in Streptomyces tsukubaensis.
AB - Tacrolimus is a widely used immunosuppressive agent in the treatment of various
clinical diseases. However, the low fermentation yield seriously limits its
further application. To stimulate tacrolimus synthesis, nine chemical elicitors
of five groups were evaluated for their effects on tacrolimus accumulation in S.
tsukubaensis. The results showed that sodium butyrate (SB), dimethylsulfoxide
(DMSO), and LaCl3 could increase tacrolimus accumulation by more than 30%.
Cumulative effects of different chemical elicitors exhibited that the highest
tacrolimus yield was improved by 64.7% (303.60 mg/L) in DMSO and La treatment,
compared to the control. To decipher possible response mechanism, a weighted
correlation network analysis (WGCNA) based on metabolomics was employed and
datasets showed 13 distinct metabolic modules and 16 hub metabolites were
possibly related to the stimulatory roles of DMSO, La, SB, and their combination
treatments. The pathway analysis further exhibited that central carbon
metabolism, amino acid metabolism, and fatty acid metabolism showed significant
differences in the above chemical elicitor treatments. Thereinto, the
carboxylation of propionyl-CoA from isoleucine and methionine degradation was
first confirmed to be the main source of methylmalonyl-CoA by RT-PCR analysis in
DMSO and La treatment. By further strengthening of the supply of methylmalonyl
CoA precursor in DMSO and La treatment, the final tacrolimus yield could reach to
372.12 mg/L, 2.02-fold higher than the control. To our knowledge, this is the
first study to unveil the potential mechanism of different chemical elicitor
stresses in S. tsukubaensis based on metabolomics, and the established
information provide valuable guidance for further improving tacrolimus
production.
PMID- 29938318
TI - Bispecific affibody molecule targeting HPV16 and HPV18E7 oncoproteins for
enhanced molecular imaging of cervical cancer.
AB - High-risk human papillomavirus (HPV16 and HPV18) are now widely recognized as
responsible for cervical cancer, which remains to be the most common gynecologic
malignancy in women worldwide. It is well known that viral oncoproteins E6/E7
play key roles in HPV-associated cervical carcinogenesis. Thus, in vivo detection
of the two oncoproteins may provide important diagnostic information influencing
patient management. More recently, affibody molecules have been demonstrated to
be a promising candidate for development as molecular imaging probes. Based on
the two monomeric affibody molecules (ZHPV16E7 and ZHPV18E7) generated in our
laboratory, here, we used a peptide linker (Gly4Ser)3 to link ZHPV16E7 and
ZHPV18E7 to develop a novel heterodimeric affibody ZHPV16E7-(Gly4Ser)3-ZHPV18E7.
Both biosensor and immunofluorescence assays have proved that the heterodimeric
affibody molecule targeted simultaneously HPV16 and HPV18E7 proteins by binding
to the viral oncoproteins. In vivo tumor-imaging experiments using the Dylight755
labeled heterodimeric affibody revealed that strongly high-contrast tumor
retention of the heterodimers occurred in both HPV16- and HPV18-derived tumors of
nude mice 0.5 h post-injection. The accumulation of Dylight755-labeled
heterodimers in tumors was achieved over 48 h. Therefore, we believe that this
novel heterodimeric affibody molecule has great potential utility in molecular
imaging in vivo and diagnosis of HPV-associated cervical cancers.
PMID- 29938319
TI - The LuxS/AI-2 system of Streptococcus suis.
AB - Quorum sensing (QS) is an important protective mechanism that allows bacteria to
adapt to its environment. A limited number of signal molecules play the key role
of transmitting information in this mechanism. Signals are transmitted between
individual bacterium through QS systems, resulting in the expression of specific
genes. QS plays an important role in a variety of bacterial processes, including
drug resistance, biofilm formation, motility, adherence, and virulence. Most Gram
positive and Gram-negative bacteria possess QS systems, mainly the LuxS/AI-2
mediated QS system. Evidence has been brought that LuxS/AI-2 system controls
major virulence determinants in Streptococcus suis and, as such, the ability of
this bacterial species to cause infections in humans and pigs. Understanding the
S. suis LuxS/AI-2 system may open up novel avenues for decreasing the drug
resistance and infectivity of S. suis. This article focuses on the progress made
to date on the S. suis LuxS/AI-2-mediated QS system.
PMID- 29938320
TI - Aroma compounds production by solid state fermentation, importance of in situ gas
phase recovery systems.
AB - Flavour and fragrance compounds are extremely important for food, feed, cosmetic
and pharmaceutical industries. In the last decades, due to the consumer's
increased trend towards natural products, a great interest in natural aroma
compounds has arisen to the detriment of chemically synthesised ones. Recently,
solid state fermentation (SSF) has been applied in the production of many
metabolites. Aroma compounds can be produced by SSF with a higher yield compared
to submerged fermentation (SmF). In SSF processes, aroma compounds can be
produced in the solid matrix or in the headspace, but they can be lost or
stripped when aeration is required. This review focuses on the production of
aroma compounds by SSF processes with a special highlight on in situ systems to
recover the volatiles released in the gaseous phase and stripped due to aeration.
Following a brief presentation of specificities of SSF processes concerning the
choice of microorganisms and the solid matrix used for the production of aroma
compounds, bioreactor aspects, factors affecting production of aroma compounds
and in situ gas phase aroma recovery systems in aerated SSF bioreactors are
discussed.
PMID- 29938321
TI - Prevention of Cardiotoxicities With Traditional and Novel Chemotherapeutic
Agents.
AB - PURPOSE OF REVIEW: This review will discuss strategies to prevent cardiotoxicity
associated with chemotherapeutics. Forty years ago, investigators identified dose
dependent cardiotoxicity related to anthracycline-based regimens. Over recent
decades, the development of more selective, mechanism-based chemotherapeutics has
been associated with both on-target and off-target adverse cardiovascular
sequelae. RECENT FINDINGS: Strategies to prevent or attenuate cardiotoxicities
include limitation of anthracycline dose, appropriate patient selection,
referral/access to cardio-oncology programs, early recognition of cardiac side
effects, active cardio-surveillance, cardio-protective medical therapy, treatment
specific concerns, and follow-up. The importance of accurate diagnosis of
cardiotoxicity is important as false-positive testing may result in inappropriate
holding or stopping potentially life-saving chemotherapy. Data to support use of
cardio-protective medical therapy to prevent chemotherapy-related cardiotoxicity
is modest at best, limited by marginal effect size, small patient numbers, and
short follow-up. The rapid growth in cardio-oncology clinics may facilitate
larger multi-center randomized controlled trials in this area.
PMID- 29938323
TI - Co-infection: the outcome of Plasmodium infection differs according to the time
of pre-existing helminth infection.
AB - Although helminth-Plasmodium coinfections are common in tropical regions, the
implications of this co-existence for the host immune response are poorly
understood. In order to understand the effect of helminth infection at different
times of coinfection on the immune response against Plasmodium infection, BALB/c
mice were intraperitoneally infected with Taenia crassiceps (Tc). At 2 (Tc2) or 8
(Tc8) weeks post-infection, mice were intravenously infected with 1 * 103
Plasmodium yoelii (Py) 17XL-parasitized red blood cells. Py 17XL-single-infected
mice developed cachexia, splenomegaly, and anemia, and died at 11 days post
infection. Importantly, Tc2 + Py-coinfected mice showed increased survival of 58%
on day 11, but developed pathology (cachexia and splenomegaly) and succumbed on
day 18 post-coinfection, this latter associated with high levels of IL-1beta and
IL-12, and reduced IFN-gamma in serum compared with Py 17XL-single-infected mice.
Interestingly, Tc8 + Py-coinfected mice showed increased survival up to 80% on
day 11 and succumbed on day 30 post-coinfection. This increased survival rate
conferred by chronic helminth infection was associated with a decreased pathology
and mixed inflammatory-type 1/anti-inflammatory-type 2 immune profile as
evidenced by the production of high levels of IL-12 and IL-10, and reduced TNF
alpha from macrophages, high levels of IL-4 and IL-10, and low levels of IFN
gamma from spleen cells. Also high serum levels of IL-1beta, TNF-alpha, IL-12, IL
4, and IL-10, but a significant reduction of IFN-gamma were observed. Together,
these data indicate that polarization of the cell-mediated response modulated by
a pre-existing helminth infection differentially impacts on the host immune
response to Py 17XL in a time-dependent manner.
PMID- 29938322
TI - Decompensated Heart Failure With Ventricular Arrhythmia: How Useful Is VT
Ablation?
AB - PURPOSE OF REVIEW: Ventricular arrhythmias are common in patients with heart
failure. Their management especially in the context of decompensated heart
failure poses a clinical challenge to modern cardiologists. In this review
article, we aim to summarise the current evidence on the epidemiology,
pathophysiology, and management of ventricular tachycardia in heart failure,
focusing primarily on the use of catheter ablation. RECENT FINDINGS: The
evolution of electro-anatomical mapping techniques and ablation catheter
technology in the recent years has paved the path for the successful application
of catheter ablation in the treatment of ventricular arrhythmias. The efficacy of
catheter ablation in the management of ventricular tachycardia in patients with
chronic heart failure has recently been the epicentre of a number of randomised
controlled trials, demonstrating promising results with regard to arrhythmia
suppression and all-cause mortality. The usefulness of catheter ablation in
decompensated heart failure has been explored to a lesser degree, primarily in
the setting of an electrical storm. Implantable cardiac defibrillators play the
most important role in improving prognosis and preventing sudden cardiac death in
patients with heart failure. Catheter ablation for the treatment of recurrent VT
in patients with chronic heart failure is an efficacious strategy that can be
applied adjunctively to or in instead of antiarrhythmic therapy, and it is highly
successful at preventing recurrent ventricular tachycardia, ICD shocks. Its
efficacy in the context of decompensated heart failure requires further research,
with current evidence rendering its use promising.
PMID- 29938324
TI - Computed tomography findings and preoperative risk factors for mortality of total
anomalous pulmonary venous connection.
AB - Detailed preoperative imaging of total anomalous pulmonary venous connection
(TAPVC) is critical to ensuring adequate surgical planning and preoperative
decision making. The purpose of this study was to describe the computed
tomography findings of TAPVC and identify morphologic death risk factors. We
conducted a retrospective study included 70 patients with TAPVC between May 2014
and June 2017 in Hunan Children's Hospital. All available clinical data and
computed tomography imaging were reviewed, and survival time was followed-up.
Life Tables analysis was used to estimate survival rates. Patient survival was
described with Kaplan-Meier curves. Cox Regression model was used to test the
potential risk factors. TAPVC was subdivided into four types. Of 70 cases, 42
(60%) had supracardiac, 13 (18.6%) had cardiac, 8 (11.4%) had infracardiac, and 7
(10%) had mixed type. Pulmonary venous obstruction (PVO) was found in 30 (42.9%)
of 70 patients in this group. Of all concurrent abnormalities, atrial septal
defect (ASD) was the most common (98.6%), followed by patent ductus arteriosus
(PDA; 31, 44.3%), and persistent left superior vena cava (PLSVC; 5, 7.1%). 1, 3,
6 and 12-month survival rates were 76, 61, 49, and 38% respectively. Risk factors
for mortality in multivariable analysis comprised PVO, McGoon index (MGI), and
mode of delivery. Various concurrent abnormalities and great morphological
heterogeneity were observed in patients with TAPVC. Patients with TAPVC had a
highest mortality in the neonatal period. PVO, smaller MGI and caesarean are
important predictors for mortality.
PMID- 29938325
TI - In vivo performances of pure Zn and Zn-Fe alloy as biodegradable implants.
AB - The disadvantage of current biodegradable metals such as Mg and Fe is the release
of hydrogen gas in vivo that can cause gas embolism and the production of
voluminous iron oxide that can cause inflammation, respectively. Such
considerations have turned focus towards Zn as an alternative. This is based on
the fact that Zn plays a crucial role in many physiological processes, as well as
potentially being biocompatible and capable of with biodegradation. As such, the
purpose of the present study was to evaluate the in vivo performance of pure Zinc
and Zn-2%Fe implants. The use of iron as an alloying element was aimed at
accelerating the corrosion rate of pure zinc by a micro-galvanic effect so as to
maintain the post-implantation biodegradation characteristics of the implant. In
vivo assessment was carried out using cylindrical disks implanted in the back
midline of 16 male Wistar rats for up to 24 weeks. Post-implantation evaluation
included monitoring the well-being of rats, weekly examination of hematological
parameters: serum Zn levels, red and white blood cell counts and hemoglobin
levels, X-ray radiography, histological analysis and corrosion rate assessment.
The results obtained in terms of well-being, hematological tests and histological
analysis of the rats indicate that the in vivo behavior of pure Zn and Zn-2%Fe
implants was adequate and in line with the results obtained by the control group
containing inert Ti-6Al-4V alloy implants. The corrosion rate of Zn-2%Fe alloy in
in vivo conditions was relatively increased compared to pure Zn due to micro
galvanic corrosion.
PMID- 29938326
TI - Potentially toxic elements in fly ash dependently of applied technology of hard
coal combustion.
AB - Coal combustion is one of the most significant anthropogenic sources of thallium
in the environment. This study presents the results of determination of thallium
and some toxic elements (Pb, Cd, As, Ni, Zn, and Cu) concentration in fly ash
produced in the coal combustion in conventional furnaces (pulverized coal furnace
and grate furnace), in a fluidized-bed furnace with circulation bed, and in a
home furnace. The high content of thallium was determined in ash produced in the
grate furnace (on average 10.7 mg/kg) and fluidized-bed furnace with circulation
bed (6.6 mg/kg). The average content of Tl in the fly ash of the pulverized coal
furnace and in the home furnace is 1.7 and 2.4 mg/kg, respectively. There was a
strong relationship between the occurrence of Tl and As, Cd, Pb, Cu, and Zn in
ash from grate and pulverized coal furnace.
PMID- 29938327
TI - Ultrastructural changes in endometrial desmosomes of desmoglein 2 mutant mice.
AB - The intercellular binding of desmosomal junctions is mediated by cadherins of the
desmoglein (Dsg) and desmocollin (Dsc) type. Dsg2 mutant mice with deletion of a
substantial segment of the extracellular EC1-EC2 domain, which is believed to
participate in homo- and heterophilic desmosomal cadherin interactions, develop
cardiac fibrosis and ventricular dilation. Widening of the intercellular cleft
and complete intercalated disc ruptures can be observed in the hearts of these
mice. Since a reduced litter size of homozygous Dsg2 mutant mice was noted and a
functional correlation between desmosomes and embryo implantation has been
deduced from animal studies, we looked for an alteration of desmosomes in uterine
endometrial epithelium. Shape and number of desmosomes as well as the expression
of Dsg2 and the desmosomal plaque protein desmoplakin (Dsp) were investigated by
electron microscopy and immunohistochemistry in 12 oestrous-dated mice (7 wild
type and 5 homozygous Dsg2 mutant mice) at the age of 9-17 weeks. The
immunohistochemical detection of Dsg2 was diminished in the mutants and the
number of desmosomes was significantly reduced as revealed by electron
microscopy. In addition, the intercellular desmosomal space measured in electron
micrographs was considerably widened in the Dsg2 mutants. The increased
intercellular spacing can be explained by the partial deletion of the
extracellular EC1-EC2 domain of Dsg2. Whether these changes explain the reduced
number of offspring of homozygous Dsg2 mutant mice remains to be further
investigated.
PMID- 29938329
TI - What indeed can be tested with an instrumental variable?
PMID- 29938328
TI - Treatment of pediatric spinal deformity with use of recombinant human bone
morphogenetic protein-2.
AB - In pediatric spine surgery nonunion is a challenging issue. Instability may cause
neurological impairment and lead to numerous surgeries in order to achieve
fusion. The use of rhBMP-2 for pediatric spinal fusion has not been widely
reported. In this study, a series of 13 children (14 procedures) that underwent
spinal rhBMP-2 application were analyzed in order to measure clinical and
radiographic outcome. Therefore, patient data, diagnosis, construct of
instrumentation, type of bone graft, quantity of BMP used, and fusion outcome
were reviewed. The study cohort included four female and nine male patients with
a mean age of 11.2 years (range 2.6-19.2 years) at the time of rhBMP-2
application. Rh-BMP-2 was used in both primary (n = 6) and revision surgery (n =
8) in patients with a high risk for the development of nonunion. The mean follow
up was 51 months (range 12-108 months). Fusion occurred in 11 patients.
Complications that may be due to application of rhBMP-2 were seen after four
operations. Three patients had an increased body temperature and in one case
prolonged wound secretion was evident, treated by local wound care or
observation. In one of these patients an extensive postoperative hematoma
occurred, necessitating surgical treatment. In conclusion, we could detect high
fusion rates following the use of rhBMP-2 in pediatric spine surgery without an
increased complication rate attributable to its application. Therefore we
consider recombinant human BMP-2 to be an option in selected pediatric spinal
procedures, especially in cases with compromised bone healing due to congenital,
systemic, or local conditions.
PMID- 29938330
TI - Nutritional status in patients with head and neck cancer undergoing radiotherapy:
a longitudinal study.
AB - PURPOSE: Patients with head and neck cancers are susceptible to malnutrition
during radiotherapy. This study aimed to determine the changes in the nutritional
status and its determinants in patients with head and neck cancer during
radiotherapy. METHODS: This prospective observational study was performed in an
outpatient Radiation Oncology clinic with a sample of 54 patients. An interview
form (including anthropometric and laboratory parameters), the Patient-Generated
Subjective Global Assessment to assess nutritional status, quality of life
scales, and toxicity criteria were used for data collection at the baseline, the
end of radiotherapy and 1 and 3 months after radiotherapy. RESULTS: While the
majority of the patients (90%) were well nourished at baseline, most of the
patients (74%) were malnourished at the end of radiotherapy (p < 0.001). During
radiotherapy, patients developed malnutrition, reflected in a decrease in food
intake, approximately 5% loss of body weight, a reduction in mid-arm upper
circumference and mid-arm muscle mass, and reduced serum protein and albumin
levels. The nutritional status was worse in oropharyngeal cancers (p = 0.021),
advanced stage (p = 0.004), use of concomitant chemotherapy (p = 0.041), and
worse toxicity (p < 0.001). Furthermore, the nutritional status was strongly
associated with the quality of life. CONCLUSIONS: This study demonstrated
negative impact of radiotherapy on the nutritional status of patients with head
and neck cancer. The study also showed the association of the nutritional status
and the quality of life. The nutritional status should be assessed during
different periods in the trajectory of treatment due to its significant
contribution to the quality of life.
PMID- 29938331
TI - Bilateral adrenal abnormalities: imaging review of different entities.
AB - Bilateral adrenal abnormalities are not infrequently encountered during routine
daily radiology practice. The differential diagnoses of bilateral adrenal
abnormalities include neoplastic and non-neoplastic entities. The bilateral
adrenal tumors include metastasis, lymphoma, neuroblastoma, pheochromocytoma,
adenoma, and myelolipoma. Non-neoplastic bilateral adrenal masses include
infectious processes and haematomas. There are different diffuse bilateral
adrenal changes such as adrenal atrophy, adrenal enlargement, adrenal
calcifications, and altered adrenal enhancement. In this pictorial review
article, we will discuss the imaging features of these entities with emphasis on
their clinical implications.
PMID- 29938332
TI - Penicillium purpurogenum Produces a Set of Endoxylanases: Identification,
Heterologous Expression, and Characterization of a Fourth Xylanase, XynD, a Novel
Enzyme Belonging to Glycoside Hydrolase Family 10.
AB - The fungus Penicillium purpurogenum grows on a variety of natural carbon sources
and secretes a large number of enzymes which degrade the polysaccharides present
in lignocellulose. In this work, the gene coding for a novel endoxylanase has
been identified in the genome of the fungus. This gene (xynd) possesses four
introns. The cDNA has been expressed in Pichia pastoris and characterized. The
enzyme, XynD, belongs to family 10 of the glycoside hydrolases. Mature XynD has a
calculated molecular weight of 40,997. It consists of 387 amino acid residues
with an N-terminal catalytic module, a linker rich in ser and thr residues, and a
C-terminal family 1 carbohydrate-binding module. XynD shows the highest identity
(97%) to a putative endoxylanase from Penicillium subrubescens but its highest
identity to a biochemically characterized xylanase (XYND from Penicillium
funiculosum) is only 68%. The enzyme has a temperature optimum of 60 degrees C,
and it is highly stable in its pH optimum range of 6.5-8.5. XynD is the fourth
biochemically characterized endoxylanase from P. purpurogenum, confirming the
rich potential of this fungus for lignocellulose biodegradation. XynD, due to its
wide pH optimum and stability, may be a useful enzyme in biotechnological
procedures related to this biodegradation process.
PMID- 29938333
TI - Saponins of Tribulus terrestris attenuated neuropathic pain induced with
vincristine through central and peripheral mechanism.
AB - The study comprises exploring the effects of saponins from Tribulus terrestris
(TT) in attenuating the neuropathic pain caused by vincristine (100 MUg/ml i.p.)
for 10 days (in two 5 day cycles with 2 days pause). Mechanical hyperalgesia and
allodynia were assessed by Randall-Sellitto and electronic von Frey tests,
respectively. Chemical- induced nociception was assessed by formalin test.
Neurophysiological effect of the extract was evaluated by recording sciatic
functional index (SFI) on the test days (7, 10, 14, and 21) and sciatic nerve
conduction velocity test (SNCV) on the last day. Inflammatory mediators (TNF
alpha, IL-1beta, and IL-6) in both sciatic nerve and brain and brain
neurotransmitters, glutamate and aspartate, were measured to support the
behavioral response. The saponins of TT-treated group were found to be effective
in the behavioral experiments, implying its activity both centrally and
peripherally in attenuating pain. The inflammatory mediators in both sciatic
nerve and brain (TNF-alpha, IL-1beta, and IL-6) were found to be attenuated with
TT saponin treatment in comparison to vincristine-treated group, indicating its
anti-inflammatory property. The excitatory neurotransmitters, L-glutamic acid and
L-aspartic acid, were also found to be attenuated with TT saponins, implying
restoration of neuronal damage and synaptic activity caused by high amount of
glutamate due to excess TNF-alpha in brain and reversing the nociceptive
threshold lowered due to aspartate. Thus, TT(S) is peripherally and centrally
active in lowering the inflammatory mediators, reversing the neuronal damage and
increasing the nociceptive threshold caused due to peripheral neuropathy.
PMID- 29938335
TI - Vestibular neuritis selectively involving posterior canal and utricle.
PMID- 29938334
TI - An important step towards a prevascularized islet macroencapsulation device
effect of micropatterned membranes on development of endothelial cell network.
AB - The development of immune protective islet encapsulation devices could allow for
islet transplantation in the absence of immunosuppression. However, the immune
protective membrane / barrier introduced there could also impose limitations in
transport of oxygen and nutrients to the encapsulated cells resulting to limited
islet viability. In the last years, it is well understood that achieving
prevascularization of the device in vitro could facilitate its connection to the
host vasculature after implantation, and therefore could provide sufficient blood
supply and oxygenation to the encapsulated islets. However, the microvascular
networks created in vitro need to mimic well the highly organized vasculature of
the native tissue. In earlier study, we developed a functional macroencapsulation
device consisting of two polyethersulfone/polyvinylpyrrolidone (PES/PVP)
membranes, where a bottom microwell membrane provides good separation of
encapsulated islets and the top flat membrane acts as a lid. In this work, we
investigate the possibility of creating early microvascular networks on the lid
of this device by combining novel membrane microfabrication with co-culture of
human umbilical vein endothelial cell (HUVEC) and fibroblasts. We create thin
porous microstructured PES/PVP membranes with solid and intermittent line
patterns and investigate the effect of cell alignment and cell interconnectivity
as a first step towards the development of a stable prevascularized layer in
vitro. Our results show that, in contrast to non-patterned membranes where HUVECs
form unorganized HUVEC branch-like structures, for the micropatterned membranes,
we can achieve cell alignment and the co-culture of HUVECs on a monolayer of
fibroblasts attached on the membranes with intermittent line-pattern allows for
the creation of HUVEC branch-like structures over the membrane surface. This
important step towards creating early microvascular networks was achieved without
the addition of hydrogels, often used in angiogenesis assays, as gels could block
the pores of the membrane and limit the transport properties of the islet
encapsulation device.
PMID- 29938336
TI - The effect of fingolimod on focal and diffuse grey matter damage in active MS
patients.
AB - INTRODUCTION: The mechanism of action of fingolimod within the central nervous
system and its efficacy in reducing/preventing both focal and diffuse grey matter
(GM) damage in active multiple sclerosis (MS) are not completely understood.
METHODS: In this longitudinal, 2-year prospective, phase IV, single-blind study,
40 MS patients treated with fingolimod and 39 untreated age, gender, and
disability-matched MS patients were enrolled. Each patient underwent a
neurological examination every 6 months and a 3T MRI at the beginning of the
treatment and after 24 months. The accumulation of new cortical lesions (CLs) and
the progression of regional GM atrophy were compared between the two groups.
RESULTS: At the end of the study (T24), the percentage of patients with new CLs
(13.5 vs. 89%, p < 0.001) and the percentage of GM volume change was lower in the
treated group (p < 0.001). The regional analysis revealed that the treated group
had also less volume loss in thalamus, caudatus, globus pallidus, cingulate
cortex, and hippocampus (p < 0.001), as well as in, cerebellum, superior frontal
gyrus, and insular-long gyrus (p < 0.05). Patients with no evidence of disease
activity were 60% in the treated group and 10% in the untreated group (p <
0.001). CONCLUSIONS: These results suggest a possible protective effect of
fingolimod on focal and diffuse GM damage.
PMID- 29938337
TI - Myelin oligodendrocyte glycoprotein-positive optic neuritis masquerading as
pseudotumor cerebri at presentation.
AB - Optic neuritis (ON) is a common clinical manifestation in myelin oligodendrocyte
glycoprotein (MOG) antibody-associated disease. Other clinical manifestations
include acute demyelinating encephalomyelitis, transverse myelitis and
neuromyelitis optica spectrum disorders. Uncommon presentations of MOG-positive
disease have recently been reported. ON in MOG-positive disease commonly involves
the anterior portion of both optic nerves, leading to bilateral disc swelling.
During the early stages of ON, in the setting of bilateral disc swelling and
pain, patients may initially be suspected as pseudotumor cerebri (PTC). In this
study, we report five cases presenting early in the course of MOG-IgG-related ON,
which were misdiagnosed as PTC in the emergency department. MOG-IgG-positive ON
requires timely treatment to prevent RNFL and vision loss secondary to the high
relapse rate associated with these antibodies. Our aim is to increase the
awareness of the unique findings of MOG-IgG-positive ON, which may initially
mimic PTC, thereby delaying treatment.
PMID- 29938338
TI - Calculation algorithms for breath-by-breath alveolar gas exchange: the unknowns!
AB - PURPOSE: Several papers (algorithm papers) describe computational algorithms that
assess alveolar breath-by-breath gas exchange by accounting for changes in lung
gas stores. It is unclear, however, if the effects of the latter are actually
considered in literature. We evaluated dissemination of algorithm papers and the
relevant provided information. METHODS: The list of documents investigating
exercise transients (in 1998-2017) was extracted from Scopus database. Documents
citing the algorithm papers in the same period were analyzed in full text to
check consistency of the relevant information provided. RESULTS: Less than 8%
(121/1522) of documents dealing with exercise transients cited at least one
algorithm paper; the paper of Beaver et al. (J Appl Physiol 51:1662-1675, 1981)
was cited most often, with others being cited tenfold less. Among the documents
citing the algorithm paper of Beaver et al. (J Appl Physiol 51:1662-1675, 1981)
(N = 251), only 176 cited it for the application of their algorithm/s; in turn,
61% (107/176) of them stated the alveolar breath-by-breath gas exchange
measurement, but only 1% (1/107) of the latter also reported the assessment of
volunteers' functional residual capacity, a crucial parameter for the application
of the algorithm. Information related to gas exchange was provided consistently
in the methods and in the results in 1 of the 107 documents. CONCLUSION:
Dissemination of algorithm papers in literature investigating exercise transients
is by far narrower than expected. The information provided about the actual
application of gas exchange algorithms is often inadequate and/or ambiguous. Some
guidelines are provided that can help to improve the quality of future
publications in the field.
PMID- 29938339
TI - Creation and evaluation of a cancer survivorship curriculum for pediatric
resident physicians.
AB - PURPOSE: There is a paucity of formal clinician education concerning cancer
survivorship care, which produces care barriers and poorer outcomes for survivors
of childhood cancer. To address this, we implemented a curriculum in childhood
cancer survivorship care for pediatric residents at the University of California,
Los Angeles (UCLA). We examined the efficacy of this curriculum following program
completion. METHODS: A case-based curriculum was created and integrated within
existing educational structures using Kern's model. We utilized the retrospective
pre-posttest method to evaluate participating residents' knowledge, clinical
skills, and attitudes towards cancer survivorship topics before and after
receiving the curriculum. Pre-posttest items were compared using paired t tests
and one-sided binomial tests. We analyzed free-response question items for major
themes using constant comparative methods. RESULTS: Thirty-four residents
completed the curriculum and its evaluation. Each assessment item significantly
increased from pre- to post-curriculum; p < 0.05. Greater than 40% of residents
improved in all but one assessment item post-curriculum; p < 0.05. Residents
reported the curriculum enhanced their pediatric knowledge base (M = 3.24; SD =
0.65) and would recommend it to other residency programs; M = 3.24; SD = 0.69.
Major themes included residents' request for additional oncofertility
information, training in counseling survivors, and cancer survivorship training
opportunities. CONCLUSIONS: A cancer survivorship curriculum can successfully
increase trainees' knowledge, clinical skills, and comfort in discussing topics
relevant to survivorship care. IMPLICATIONS FOR CANCER SURVIVORS: With increasing
numbers of childhood cancer survivors living into adulthood, residents will
likely treat this population regardless of intended career path. This curriculum
represents one method to deliver formal cancer survivorship training.
PMID- 29938340
TI - Investigating the effect of STN-DBS stimulation and different frequency settings
on the acoustic-articulatory features of vowels.
AB - INTRODUCTION: Parkinson's disease (PD) is the second most frequent progressive
neuro-degenerative disorder. In addition to motor symptoms, nonmotor symptoms and
voice and speech disorders can also develop in 90% of PD patients. The aim of our
study was to investigate the effects of DBS and different DBS frequencies on
speech acoustics of vowels in PD patients. METHODS: The study included 16
patients who underwent STN-DBS surgery due to PD. The voice recordings for the
vowels including [a], [e], [i], and [o] were performed at frequencies including
230, 130, 90, and 60 Hz and off-stimulation. The voice recordings were gathered
and evaluated by the Praat software, and the effects on the first (F1), second
(F2), and third formant (F3) frequencies were analyzed. RESULTS: A significant
difference was found for the F1 value of the vowel [a] at 130 Hz compared to off
stimulation. However, no significant difference was found between the three
formant frequencies with regard to the stimulation frequencies and off
stimulation. In addition, though not statistically significant, stimulation at 60
and 230 Hz led to several differences in the formant frequencies of other three
vowels. CONCLUSION: Our results indicated that STN-DBS stimulation at 130 Hz had
a significant positive effect on articulation of [a] compared to off-stimulation.
Although there is not any statistical significant stimulation at 60 and 230 Hz
may also have an effect on the articulation of [e], [i], and [o] but this effect
needs to be investigated in future studies with higher numbers of participants.
PMID- 29938341
TI - Relation between lipoprotein-associated phospholipase A2 mass and incident
ischemic stroke severity.
AB - BACKGROUND: Manifestations of ischemic stroke vary widely, and serum biomarkers
may be useful for stratification of risk of severe stroke. This study evaluated
the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and
initial severity. METHODS: We employed a retrospective analysis on our hospital
based registry and recruited 488 first-onset ischemic stroke patients admitted
within 24 h after onset and with Lp-PLA2 mass measured. Stroke severities
evaluated by National Institutes of Health Stroke Scale (NIHSS) were compared
between Lp-PLA2 categories dichotomized by median. Multivariate logistic
regression was used to detect the independent risk factors of severe stroke
(NIHSS >= 7) and receiver operator curve (ROC) was constructed to detect the
value of addition of Lp-PLA2 to the model of other risk factors for predicting
severe stroke. RESULTS: Of the overall patients, the median admission NIHSS
scores was 3 and 28.1% had severe manifestation. Admission NIHSS scores were
different between patients of Lp-PLA2 above and under the median (median NIHSS 4
vs. 3, P < 0.001). Lp-PLA2 levels was correlated with admission NIHSS (r = 0.268,
P < 0.001). Logistic regression showed Lp-PLA2 category (OR 2.37, 95%CI 1.44
3.90, P < 0.001) and levels per 100 ng/ml (OR 1.69, 95%CI 1.35-2.11, P < 0.001)
were both independently associated with severe stroke. Addition of Lp-PLA2
category and levels to other independent risk factors both increased the area
under curves (from 0.676 to 0.718 with category and 0.734 with levels).
CONCLUSION: Lp-PLA2 was independently related to admission severity in ischemic
stroke patients, implying a potential predictive value of Lp-PLA2 for severe
stroke in prevention.
PMID- 29938342
TI - Delineation of the functional and structural properties of the glutathione
transferase family from the plant pathogen Erwinia carotovora.
AB - Erwinia carotovora, a widespread plant pathogen that causes soft rot disease in
many plants, is considered a major threat in agriculture. Bacterial glutathione
transferases (GSTs) play important roles in a variety of metabolic pathways and
processes, such as the biodegradation of xenobiotics, protection against abiotic
stress, and resistance against antimicrobial drugs. The GST family of canonical
soluble enzymes from Erwinia carotovora subsp. atroseptica strain SCRI1043
(EcaGSTs) was investigated. Genome analysis showed the presence of six putative
canonical cytoplasmic EcaGSTs, which were revealed by phylogenetic analysis to
belong to the well-characterized GST classes beta, nu, phi, and zeta. The
analysis also revealed the presence of two isoenzymes that were phylogenetically
close to the omega class of GSTs, but formed a distinct class. The EcaGSTs were
cloned and expressed in Escherichia coli, and their catalytic activity toward
different electrophilic substrates was elucidated. The EcaGSTs catalyzed
different types of reactions, although all enzymes were particularly active in
reactions involving electrophile substitution. Gene and protein expression
profiling conducted under normal culture conditions as well as in the presence of
the herbicide alachlor and the xenobiotic 1-chloro-2,4-dinitrobenzene (CDNB)
showed that the isoenzyme EcaGST1, belonging to the omega-like class, was
specifically induced at both the protein and mRNA levels. EcaGST1 presumably
participates in counteracting the xenobiotic toxicity and/or abiotic stress
conditions, and may therefore represent a novel molecular target in the
development of new chemical treatments to control soft rot diseases.
PMID- 29938343
TI - Interrogation of a longitudinal, national pharmacy claims dataset to explore
factors that predict the need for add-on therapy in older and socioeconomically
disadvantaged Australians with type 2 diabetes mellitus patients (T2DM).
AB - PURPOSE: The management of type 2 diabetes mellitus (T2DM) is complex. The aim of
this work is to explore factors that predict the need for add-on therapy in
patients with T2DM in the community. METHODS: We accessed longitudinal, pharmacy
payment claim records from the national Pharmaceutical Benefits Scheme (PBS)
(Subsidises costs of medicines: government pays difference between patient co
payments, lower in concessional patients, and additional cost of drug.) for the
period January 2006 to September 2014 (EREC/MI3127) from a 10% random sample of
the Australian population validated to be representative of the population by the
Australian Bureau of Statistics (ABS). Likely, T2DM patients were identified as
those having been dispensed a single anti-hyperglycaemic drug (monotherapy). The
time taken and possible factors that might lead to the addition of a second
therapy were examined. An examination was made of trends in the co-prescription
of either antihypertensive or anti-hyperlipidaemic agents in relation to the time
(+/- 3 years) of initiating an anti-hyperglycaemic agent. RESULTS: Most (83%)
presumed T2DM patients were initiated with metformin. The average time until the
second agent was added was 4.8 years (95% CI 4.7-4.9). Satisfactory adherence,
age, male gender, initiating therapy after 2012 and initiating with a
sulphonylurea drug all were significant risks for add-on therapy. There was no
overall trend in the initiation of antihypertensive and/or anti-hyperlipidaemic
agents with respect to the time of anti-hyperglycaemic initiation. CONCLUSION:
The usefulness of a longitudinal dataset of pharmacy-claim records is
demonstrated. Over half of all older and socioeconmically disadvantaged T2DM
patients captured in this longitudinal claims database will be prescribed a
second anti-hyperglycaemic agent within 5 years of their first drug therapy.
Several factors can predict the risk of prescription of add-on therapy, and these
should be considered when prescribing medications to treat T2DM.
PMID- 29938345
TI - Efficacy of aromatherapy to reduce labor pain.
PMID- 29938344
TI - Association of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast
cancer patients: results of a global screening array.
AB - PURPOSE: Cyclophosphamide and doxorubicin (adjuvant chemotherapy) are commonly
used to treat breast cancer patients. Variation in the genes involved in
pharmacodynamics and pharmacokinetics of these drugs plays an important role in
prediction of drug response and survival. The present study was carried out with
an aim to evaluate the variation in all the genes involved in pharmacokinetic and
pharmacodynamics pathways of cyclophosphamide and doxorubicin, and correlate
specific variants with disease outcome in breast cancer patients from the Malwa
region of Punjab. METHODS: A total of 250 confirmed breast cancer patients were
involved in the study. Genotyping was performed on an Illumina Infinium HD assay
platform using a Global Screening Array (GSA) microchip. GenomeStudio (Illumina,
Inc.) was used for data preprocessing and a p value less than or equal to 5 * 10
8 was considered statistically significant. To rule out the influence of
confounding risk factors, a step-wise multivariate regression analysis was
carried out to evaluate the association of genotype with overall clinical
outcome. RESULTS: Two gene variants, CYP2C19 (G681A) and ALDH1A1*2 (17 bp
deletion), were found to be significantly associated with the disease outcome,
including overall survival, recurrence and metastasis, in breast cancer patients
on adjuvant therapy. Both these genes are involved in the pharmacokinetics of
cyclophosphamide. However, none of the variants in the genes involved in
pharmacokinetics and pharmacodynamics of doxorubicin were found to have any
significant impact on disease outcome in the studied group. CONCLUSION: CYP2C19
(G681A) variant and ALDH1A1*2 emerged as two important biomarkers associated with
bad outcome in breast cancer patients on adjuvant therapy.
PMID- 29938346
TI - Tocolysis with the beta2-sympathomimetic fenoterol does not increase the
occurrence of infantile hemangioma in preterm and term infants.
AB - PURPOSE: beta2-sympathomimetics are used in obstetrics as tocolytic agents,
despite a remarkable profile of side effects. Recently, the beta2-sympathomimetic
tocolytic drug hexoprenaline was identified as an independent risk factor for the
development of infantile hemangioma (IH) in preterm infants. The aim of this
study was to evaluate whether this observed effect was applicable to other beta2
mimetic tocolytic agents like fenoterol. METHODS: Clinical prospectively
collected data of all infants born between 2001 and 2012 and admitted to the
neonatal intensive care unit (NICU) at Heidelberg University Hospital and
respective maternal data were merged. For the current retrospective cohort study,
cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for
birth weight, gestational age, gender and multiple gestations. Prenatal exposure
to fenoterol and perinatal outcome were analyzed in the total cohort and in
subgroups. RESULTS: N = 5070 infants were admitted to our neonatal department,
out of which n = 172 infants with IH were identified and compared to n = 596
matched controls. Exposure to fenoterol was not associated with a higher rate of
IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a
subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR
1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to
glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI
0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared
to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were
confirmed by our large study cohort and included female gender, low birth weight,
preterm birth and multiple gestations (all p < 0.005). CONCLUSIONS: Exposure to
fenoterol during pregnancy does not increase the occurrence of IH. Further
studies are needed to explore differences in the risk profiles of different beta2
sympathomimetic tocolytic drugs.
PMID- 29938347
TI - High-density lipoproteins (HDL) composition and function in preeclampsia.
AB - PURPOSE: To evaluate (a) the properties of high-density lipoproteins
(HDL)/cholesterol, which include apolipoprotein A-1 (ApoA1) and paraoxonase1
(PON1), both are negative predictors of cardiovascular risk and (b) HDL function,
among women with preeclampsia (PE). PE is a multi-system disorder, characterized
by onset of hypertension and proteinuria or other end-organ dysfunction in the
second half of pregnancy. Preeclampsia is associated with increased risk for
later cardiovascular disease. The inverse association between HDL, cholesterol
levels and the risk of developing atherosclerotic cardiovascular disease is well
established. METHODS: Twenty-five pregnant women [19 with PE and 6 with normal
pregnancy (NP)] were recruited during admission for delivery. HDL was isolated
from blood samples. PON1 activity and HDL were analyzed. An in vitro model of
endothelial cells was used to evaluate the effect of HDL on the transcription
response of vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric
oxide synthase (eNOS) mRNA expression. RESULTS: PON1 activity (units/ml serum)
was lower in the PE group compared to normal pregnancy (NP) (6.51 +/- 0.73 vs.
9.98 +/- 0.54; P = 0.015). Increased ApoA1 was released from PE-HDL as compared
to NP-HDL (3.54 +/- 0.72 vs. 0.89 +/- 0.35; P = 0.01). PE-HDL exhibited increased
VCAM-1 mRNA expression and decreased eNOS mRNA expression on TNF-alpha stimulated
endothelial cells as compared to NP-HDL. CONCLUSIONS: HDL from women with PE
reduced PON1 activity and increased ApoA1 release from HDL particles. This
process was associated with increased HDL diameter, suggesting impaired HDL anti
oxidant activity. These changes might contribute to higher long-term
cardiovascular risks among women with PE.
PMID- 29938348
TI - Considerations Related to the Definition, Measurement and Analysis of Perceived
Motor Competence.
AB - The promotion of motor competence is integral to a holistic view of children's
development. Motor development models address the potential role of actual and
perceived motor competence, physical activity and health-related fitness in
children's health. Actual motor competence and optimal levels of perceived motor
competence seem to be key for engaging children and adolescents in physical
activity and sports. Commonly, the assessment of perceived motor competence is
carried out by using instruments originally developed to assess different
constructs of physical self-perception with the consequent error assumed. The aim
of this article is to therefore offer clarification regarding the concept of
perceived motor competence in terms of the conceptual and theoretical framework
used for its explanation. A hierarchical and multidimensional structure of global
self-concept is proposed with perceived motor competence considered as a
subdomain of perceived sport/athletic competence (depending on the age or stage
of development of the child) and subdivided into different subdomains of
perceived competence in stability, locomotion, object control and active play
skills. In order to improve consistency in the approach to assessment, it is
desirable that researchers report an agreed definition for the construct of
perceived motor competence so that readers can recognise the assumptions within
the study accurately. Furthermore, it is suggested that instruments characterised
by an alignment between actual and perceived motor competence assessments will
help us understand more about children's motor perceptions.
PMID- 29938349
TI - Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease:
Implications for Prognosis and Treatment.
AB - PURPOSE OF REVIEW: The increased cardiovascular disease (CVD) risk in subjects
with type 2 diabetes (T2D) is well established. This review collates the
available evidence and assesses the shared genetic background between T2D and
CVD: the causal contribution of common risk factors to T2D and CVD and how
genetics can be used to improve drug development and clinical outcomes. RECENT
FINDINGS: Large-scale genome-wide association studies (GWAS) of T2D and CVD
support a shared genetic background but minimal individual locus overlap.
Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS
of CVD, T2D and their common risk factors provided limited evidence for
individual locus overlap. Distinct but functionally related pathways were
enriched for CVD and T2D genetic associations reflecting the lack of locus
overlap and providing some explanation for the variable associations of common
risk factors with CVD and T2D from MR analyses.
PMID- 29938350
TI - Content of PAHs in soil of a hazel orchard depending on the method of weed
control.
AB - PAHs belong to persistent organic pollutants (POPs) found in the natural
environment. They eventually accumulate in the highest quantities in soil. The
purpose of this study has been to determine quantities of PAHs in soil depending
on the method applied to control weeds in rows of a 4-year plantation of hazel
(mulch fabric, bark chips, sawdust, manure compost, bare fallow, chemical fallow,
grass sward). The highest concentration of PAHs (16 PAHs) was found in soil kept
as bare fallow. The second most abundant concentration of these compounds was
determined in soil under grass sward, followed by soil under sawdust, chemical
fallow, and fabric. Less of these compounds accumulated in soil mulched with bark
chips. The best method for protection of orchard soil against the accumulation of
unwanted and toxic PAHs was mulching with manure compost. In most cases, lower
concentrations of PAHs (total 16) were found in the subsoil (30-60 cm) than in
the topmost soil layer, except the soil covered with mulch fabric, where fourfold
more PAHs accumulated.
PMID- 29938351
TI - Crystal structure, DFT calculations and evaluation of 2-(2-(3,4
dimethoxyphenyl)ethyl)isoindoline-1,3-dione as AChE inhibitor.
AB - Dioxoisoindolines have been included as a pharmacophore group in diverse drug
like molecules with a wide range of biological activity. Various reports have
shown that phthalimide derivatives are potent inhibitors of AChE, a key enzyme
involved in the deterioration of the cholinergic system during the development of
Alzheimer's disease. In the present study, 2-(2-(3,4
dimethoxyphenyl)ethyl)isoindoline-1,3-dione was synthesized, crystallized and
evaluated as an AChE inhibitor. The geometric structure of the crystal and the
theoretical compound (from molecular modeling) were analyzed and compared,
finding a close correlation. The formation of the C6-H6...O19 interaction could
be responsible for the non-negligible out of phenyl plane deviation of the C19
methoxy group, the O3 from the carbonyl group lead to C16-H16...O3i
intermolecular interactions to furnish C(9) and C(14) infinite chains within the
(- 4 0 9) and (- 3 1 1) families of planes. Finally, the biological experiments
reveal that the isoindoline-1,3-dione exerts a good competitive inhibition on
AChE (Ki = 0.33-0.93 mM; 95% confidence interval) and has very low acute toxicity
(LD50 > 1600 mg/kg) compared to the AChE inhibitors currently approved for
clinical use.
PMID- 29938352
TI - ZNF521 Has an Inhibitory Effect on the Adipogenic Differentiation of Human
Adipose-Derived Mesenchymal Stem Cells.
AB - Mesenchymal stem cells (MSCs) are multipotent progenitors present in the bone
marrow stroma and in subcutaneous abdominal fat, an abundant and easily
accessible source of MSCs with the ability to differentiate along multiple
lineage pathways. The stem cell-associated transcription co-factor Zinc Finger
Protein 521 (ZNF521/zfp521) has been implicated in the control of the homeostasis
of hematopoietic, neural and osteo-adipogenic progenitors. Here we document
through the analysis of a panel of human adipose-derived stem cells (hADSCs),
that ZNF521 strongly inhibits the generation of mature adipocytes. Enforced
overexpression of ZNF521 in these cells resulted in a significant delay and
reduction in adipocyte differentiation upon exposure to inducers of adipogenesis.
Of particular relevance, ZNF521 was able to inhibit the expression of ZNF423,
recently identified as an essential commitment factor necessary for the
generation of pre-adipocytes. Conversely, silencing of ZNF521 was found to
significantly enhance the adipogenic differentiation of hADSCs. Inhibition of
adipogenesis by ZNF521 was at least in part due to inhibition of EBF1. Taken
together, these results confirm a role for ZNF521 as a key negative regulator of
adipocyte differentiation of hADSCs.
PMID- 29938353
TI - Doxycycline treatment for Dirofilaria immitis in dogs: impact on Staphylococcus
aureus and Enterococcus antimicrobial resistance.
AB - Doxycycline is an antibiotic that, in addition to the classic antibacterial use,
is also prescribed to fight parasitic diseases, like heartworm disease in dogs.
Despite the concern that the overuse of this antibiotic may decrease
susceptibility of clinically important bacteria, the consequences of the
prolonged doxycycline therapy in heartworm-infected dogs have never been studied
before. We have analyzed the impact of this therapy on Staphylococcus aureus and
Enterococcus antimicrobial resistance. In this study, 17 heartworm-infected dogs
(10 that had completed the doxycycline treatment and 7 dogs that had not yet
begun) were included. Twenty-four isolates of Staphylococcus aureus were obtained
from two locations of each dog. After treatment, 73.3% of isolates were resistant
to at least one antibiotic but only 22.2% of isolates before treatment. Most of
doxycycline resistant isolates were obtained from dogs that have received
treatment. Erythromycin resistance or intermediate susceptibility was detected in
45.6% of isolates, most of them from dogs after treatment. For Enterococci, 48
isolates were obtained from fecal samples (25 before treatment and 23 after
treatment). Before treatment, 32% of isolates were resistant at least to one
antibiotic while after, this data increase up to 65%. Comparing isolates before
and after treatment, a clear increase in resistance to doxycycline (12% against
21.74%) and erythromycin (20% against 39.13%) was observed. Although the present
work is a preliminary research, the results encourages the development of further
studies to determinate the effect of prolonged doxycycline therapy on
antimicrobial resistance.
PMID- 29938354
TI - The effect of ammonia on canine polymorphonuclear cells.
AB - Hyperammonaemia is a common complication of liver disease in dogs. High
concentrations of ammonia can be detrimental to dogs with liver disease for
several reasons, notably by causing hepatic encephalopathy (HE) which describes
the wide range of neurological abnormalities ranging from altered behaviour to
seizures that are well recognised complications in dogs with hepatic disorders.
In human patients with liver disease, hyperammonaemia has also been linked to the
development of other systemic complications such as dysregulation of the innate
immune system. In contrast, the effects of hyperammonaemia on the canine innate
immune system is currently unknown. The aim of this study was to investigate the
effects of ammonia on the oxidative burst activity of canine polymorphonuclear
cells in vitro. Blood obtained from healthy dogs (n = 8) was incubated with
escalating concentrations of ammonia ranging from 0 to 250 MUM, and the
percentage of cells experiencing an oxidative burst was evaluated using a
commercial kit (PhagoburstTM) and flow cytometry. The spontaneous oxidative burst
was evaluated without stimulation and also following stimulation with E coli. The
pH of the blood was also measured at the differing ammonia concentrations. There
was an increase in the percentage of cells experiencing a spontaneous oxidative
burst from ammonia concentrations of 125 MUM (p = <0.05) and above (p = <0.01),
with a 4.9 fold increase at 200 MUM (p = < 0.001). In those cells stimulated with
E coli, incubation with increasing ammonia concentrations did not result in a
significant difference in oxidative burst from baseline (p = 0.953). There was no
statistically significant difference between the pH of the blood at the various
ammonia concentrations (p = 0.2) suggesting that the difference in spontaneous
oxidative burst was due to the ammonia rather than simply a change in pH
conditions. In summary, the spontaneous oxidative burst of neutrophils was
significantly increased from baseline. This supports a potential role of ammonia
in contributing to innate immune system dysfunction in dogs with liver disease,
and may present a future therapeutic target.
PMID- 29938355
TI - Friedreich Ataxia: Diagnostic Yield and Minimal Frequency in South Brazil.
AB - Friedreich ataxia (FRDA) is an autosomal recessive disorder due to mutations in
the FXN gene. FRDA is characterized by the classical triad of ataxia, absent
reflexes, and Babinski sign, but atypical presentations might also occur. Our
aims were to describe the proportion of FRDA diagnoses in suspected families
living in Rio Grande do Sul, South Brazil, and to estimate a minimum frequency of
symptomatic subjects. Subjects that were evaluated by molecular analysis for FRDA
at the Hospital de Clinicas de Porto Alegre were identified in our files.
Patients' clinical manifestation and phenotypes were described and compared. The
number of FRDA subjects alive in the last 5 years was determined. One hundred
fifty-six index cases (families) were submitted to evaluation of GAA repeats at
FXN since 1997: 27 were confirmed as FRDA patients. Therefore, the diagnostic
yield was 17.3%. Proportion of classical, late onset, and retained reflexes
subphenotypes were similar to those described by other studies. A minimum
prevalence was estimated as 0.20:100.000 inhabitants. In conclusion, we verified
that this FRDA population displayed the usual clinical characteristics, but with
a lower period prevalence than those obtained in populations from Europe.
PMID- 29938356
TI - Clinical practice: recognizing child sexual abuse-what makes it so difficult?
AB - : Recognizing child sexual abuse (CSA) in children is difficult, as there can be
many hurdles in the assessment of alleged CSA. With this paper, we try to improve
the recognition of CSA by discussing: (1) the difficulties regarding this matter
and (2) the diagnostic evaluation of alleged CSA, combining both practical
clinical recommendations based on recent research. Children are restrained to
disclose CSA due to various reasons, such as fears, shame, and linguistic or
verbal limitations. Associations between CSA and urogenital or gastrointestinal
symptoms, internalizing and externalizing behavioral problems, post-traumatic
stress symptoms, and atypical sexual behavior in children have been reported.
However, these symptoms are non-specific for CSA. The majority of sexually abused
children do not display signs of penetrative trauma at anogenital examination.
Diagnosing a STI in a child can indicate CSA. However, other transmission routes
(e.g., vertical transmission, auto-inoculation) need to be considered as well.
CONCLUSION: The assessment consists of medical interview and child interview
(parents and child separate and together) with special attention to the child's
development and behavior (problems), psychosocial situation and physical
complaints, the child's mental health, and the child's trauma history; anogenital
examination should be done in all cases of alleged CSA. The examination should be
documented by photo or video graphically. Recent research suggests that
videography may be the preferred method, and testing on STIs. The assessment
should be done multidisciplinary by experienced professionals. Health-care
professionals who care for children need to know how child protective agencies
and law enforcement are organized. In case there are concerns about a child's
safety, the appropriate authorities should be alarmed. What is Known: * Sexual
abuse in children often remains unrecognized in the majority of cases. What is
New: * Research suggests that videographic documentation is preferred above
photographic documentation for anogenital examination; observations of children's
behavioral reactions during examinations might be valuable in the evaluation of
suspected sexual abuse; nucleic acid amplification testing can be used on vaginal
swabs or urine samples for chlamydia and gonorrhea; the CRIES-13 and the CAPS-CA
can be used to assess trauma-symptoms in children after sexual abuse.
PMID- 29938357
TI - Interactions of alcohol and postmenopausal hormone use in regards to mammographic
breast density.
AB - PURPOSE: We investigated the association of alcohol intake with mammographic
breast density in postmenopausal women by their hormone therapy (HT) status.
METHODS: This study included 2,100 cancer-free postmenopausal women within the
Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density
(PD), absolute dense (DA), and non-dense areas (NDA) were measured from digitized
film mammograms using a computer-assisted thresholding technique; all measures
were square root transformed. Alcohol consumption was assessed with a food
frequency questionnaire (0, < 5, and >= 5 g/day). Information regarding breast
cancer risk factors was obtained from baseline or biennial questionnaires closest
to the mammogram date. We used generalized linear regression to examine
associations between alcohol and breast density measures in women with no HT
history, current, and past HT users. RESULTS: In multivariable analyses, we found
no associations of alcohol consumption with PD (p trend = 0.32) and DA (p trend =
0.53) and an inverse association with NDA (beta = - 0.41, 95% CI - 0.73, - 0.09
for >= 5 g/day, p trend < 0.01). In the stratified analysis by HT status, alcohol
was not associated with PD in any of the strata. We found a significant inverse
association of alcohol with NDA among past HT users (beta = - 0.79, 95% CI -
1.51, - 0.07 for >= 5 g/day, p trend = 0.02). There were no significant
interactions between alcohol and HT in relation to PD, DA, and NDA (p interaction
= 0.19, 0.42, and 0.43, respectively). CONCLUSIONS: Our findings suggest that
associations of alcohol with breast density do not vary by HT status.
PMID- 29938358
TI - Imaging the dynamic deposition of cell wall polymer in xylem and phloem in
Populus * euramericana.
AB - MAIN CONCLUSION: Both G units and S units deposited in the whole lignification
process of xylem fiber. The topochemical variations in newly formed xylem and
phloem of Populus * euramericana were investigated by combined microscopic
techniques. During xylem formation, earlier cell wall deposition in vessel and
afterwards in the neighboring fiber was observed in situ. Raman images in xylem
fiber emphasized that cell wall deposition was an ordered process which
lignification started in cell corner following carbohydrates deposition. Higher
deposition speed of carbohydrates was revealed at the beginning of the cell wall
differentiation, and the syringyl (S) units deposition was more pronounced
compared with guaiacyl (G) units at the earlier stage of lignification. The
comparative analysis of cell wall composition in phloem fiber indicated that
phloem formed earlier than xylem and the distribution of lignin monomers varied
significantly with phloem fiber location. Furthermore, an interesting phenomenon
was found that the outermost phloem fiber near the periderm displayed a
multilayered structure with alternating broad and narrow layer, and the broad
lamellae showed higher concentration of carbohydrates and S lignin. The
cytological information including cell wall composition and lignin structure of
xylem and phloem might be helpful to understand the wood growth progresses and
facilitate utilization of woody plants.
PMID- 29938359
TI - Comment on McPhail's (2018) "Age of Onset in Pedohebephilic Interests".
PMID- 29938360
TI - GnRH Antagonist and Antipsychotic Medication for Pedophilia Comorbid with
Schizophrenia and Intellectual Disability.
PMID- 29938361
TI - Painful swelling in the proximal third of the arm.
PMID- 29938362
TI - Polypectomy versus surgery in early colon cancer: size and location of colon
cancer affect long-term survival.
AB - BACKGROUND AND AIMS: The colon cancer survival rate is significantly affected by
location, stage, and size of the cancer. Polypectomy was shown be as equally
effective as surgery in early-stage colon cancer, but there have been no
established clinical guidelines in the management of colon cancer based on the
size of the polyp or the tumor location. The aim of our study was to assess the
early-stage colon cancer-specific survival rate in patients who underwent
endoscopic polypectomy versus surgery, based on size and location of tumor in
early-stage colon cancer. METHODS: This is a population-based nationwide study in
the USA. RESULTS: Of 13,157 patients, 15.5% underwent endoscopic treatment and
84.5% underwent surgical therapy. For early cancer tumors located in the left
colon, polypectomy yielded comparable 5-year survivals to surgery irrespective of
size of the tumors. Five-year early cancer-specific survivals were similar for
tumors located in the right colon that were < 20 mm in size (94.5 vs 94.3%, p
value = 0.94). However, tumors > 20 mm in size that were located in the right
colon had better survivals when treated surgically compared to those treated with
polypectomy (20-39 mm: 91.8 vs 74.2%; >= 40 mm: 92.4 vs 60%, both p values <
0.01). Similar results were obtained on propensity score analysis. CONCLUSIONS:
Polypectomy was as effective as surgical therapy for small tumors. For larger
tumors, surgical therapy is better than polypectomy for right-sided tumors, but
both are equally effective for left-sided tumors.
PMID- 29938363
TI - [Barriers to the German Society for General and Visceral Surgery (DGAV)
accreditation "Center for bariatric and metabolic surgery"].
AB - INTRODUCTION: The certification and accreditation process of the German Society
for General and Visceral Surgery (DGAV) aims to improve the quality of care and
enhance transparency in accredited centers. To achieve these goals a high level
of infrastructural and staffing requirements are set out by the DGAV. AIMS: The
Surgical Working Group on Obesity Treatment and Metabolic Surgery (CAADIP) survey
2017 of the members of the German Bariatric Society aimed to identify the
perceived and encountered barriers in the DGAV accreditation process. METHODS:
Between February and March 2017 an online poll was conducted of all members of
the CAADIP on topics pertaining to the accreditation process. RESULTS: A total of
214 (51%) CAADIP members participated in the poll, 47% reported that they worked
at a non-certified center and 53% worked at a DGAV certified center. Of these,
68% reported employment in a unit with the lowest accreditation level, 21% in an
intermediate level center, 11% reported employment in a unit with the highest
accreditation level (Center of Excellence) and 86% of those currently working in
non-accredited units stated that they aimed for future accreditation. Reasons
stated for not having obtained accreditation were recent establishment of the new
bariatric specialty (54%), lack of bariatric case numbers (71%), lack of human
resources and infrastructure (28% and 13%, respectively). Of those surgeons in
non-accredited centers 24% stated that the hospital management had no interest in
a certification and 12% of the surgeons themselves felt that accreditation was
unnecessary. CONCLUSION: The majority of CAADIP members strived for DGAV
certification. The main barriers encountered and perceived were the specific time
(reference years) and caseload requirements.
PMID- 29938364
TI - Assessment of the cutaneous wound healing efficiency of acidic, neutral and
alkaline bacterial cellulose membrane in rat.
AB - Recent research was conducted to evaluate the healing efficiency of bacterial
cellulose (BC) as a wound dressing in different pHs and its possibility of being
a smart wound dressing that can indicate pHs. BC was produced by environmentally
isolated bacterial strains. After washing the best achieved BC, it was floated in
normal saline with different pHs with phenol red used as a pH indicator. Finally
the wound healing effects of the acidic, neutral and alkaline BC membranes were
evaluated in rat cutaneous wounds. Results showed that one of the isolates which
its partial 16srRNA genome had 95% similarity with Gluconacetobacter intermedius,
had the thickest layer. The microscopic and macroscopic evaluations showed that
the acidic BC had the best healing activity. Although the color of the films
remained unchanged during the experiments because they were transparent and thin,
these changes could not be easily seen. This suggests the use of thicker films
such as the ones which are cross linked with some materials (e.g., sterile
gauze). In conclusion the pH can affect the healing ability of natural BC and
acidic pH had the best wound healing efficiency. In future it is better to use
the acidic BC instead of natural one for different wound healing purposes.
PMID- 29938365
TI - Design, synthesis, antimicrobial and cytotoxicity study on human colorectal
carcinoma cell line of new 4,4'-(1,4-phenylene)bis(pyrimidin-2-amine)
derivatives.
AB - BACKGROUND: Pyrimidine molecules attracted organic chemists very much due to
their biological and chemotherapeutic importance. Their related fused
heterocycles are of interest as potential bioactive molecules so, we have
designed and prepared a new class of 4,4'-(1,4-phenylene)bis(pyrimidin-2-amine)
molecules and screened for their in vitro antibacterial, antifungal and
cytotoxicity studies. RESULTS: The structures of synthesized bis-pyrimidine
molecules were confirmed by physicochemical and spectral means. The synthesized
compounds were further evaluated for their in vitro biological potentials i.e.
antimicrobial activity using tube dilution method and anticancer activity against
human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B assay.
CONCLUSIONS: The biological study demonstrated that compounds s7, s8, s11, s14,
s16, s17 and s18 have shown more promising antimicrobial activity with best MIC
values than the cefadroxil (antibacterial) and fluconazole (antifungal) and
compound s3 found to have better anticancer activity against human colorectal
carcinoma (HCT116) cancer cell line.
PMID- 29938366
TI - Quorum sensing in rhizobia isolated from the spores of the mycorrhizal symbiont
Rhizophagus intraradices.
AB - Most beneficial services provided by arbuscular mycorrhizal fungi (AMF),
encompassing improved crop performance and soil resource availability, are
mediated by AMF-associated bacteria, showing key-plant growth-promoting (PGP)
traits, i.e., the production of indole acetic acid, siderophores and antibiotics,
and activities increasing the availability of plant nutrients by nitrogen
fixation and phosphate mobilization. Such functions may be affected by the
ability of AMF-associated bacteria to communicate through the production and
secretion of extracellular small diffusible chemical signals, N-acyl homoserine
lactone signal molecules (AHLs), that regulate bacterial behavior at the
community level (quorum sensing, QS). This work investigated the occurrence and
extent of QS among rhizobia isolated from AMF spores, using two different QS
reporter strains, Agrobacterium tumefaciens NTL4 pZRL4 and Chromobacterium
violaceum CV026. We also assessed the quorum quenching (QQ) activity among
Bacillus isolated from the same AMF spores. Most rhizobia were found to be quorum
signaling positive, including six isolates producing very high levels of AHLs.
The results were confirmed by microtiter plate assay, which detected 65% of the
tested bacteria as medium/high AHL producers. A 16S rDNA sequence analysis
grouped the rhizobia into two clusters, consistent with the QS phenotype. None of
the tested bacteria showed QQ activity able to disrupt the QS signaling,
suggesting the absence of antagonism among bacteria living in AMF sporosphere.
Our results provide the first evidence of the ability of AMF-associated rhizobia
to communicate through QS, suggesting further studies on the potential importance
of such a behavior in association with key-plant growth-promoting functions.
PMID- 29938367
TI - Use of fiberoductoscopy for the management of patients with pathological nipple
discharge: experience of a single center in Poland.
AB - BACKGROUND: Pathological nipple discharge (PND) is associated with serious
clinical and diagnostic issues. Fiberoductoscopy (FDS) is a new diagnostic option
in PND patients. This study summarizes our initial experience of FDS for the
management of PND patients in a single center in Poland and assesses its safety.
METHODS: A total of 256 women with PND were included in this prospective, case
controlled, single-center study between 2006 and 2014. Of the 250 patients who
underwent FDS, 154 had mammary duct lesions and 96 had no visible lesions.
Subsequently, 129 patients with lesions identified by FDS underwent
microductectomy and the lesions were pathologically evaluated. RESULTS: The mean
duration of FDS examination was 17 min. The most frequent intraductal lesion was
amputation of a duct (35.1%), followed by circular narrowing or hyperplasia
(22.7%). Final histological findings were unremarkable in 11.6% of cases, whereas
mammary duct papilloma, duct ectasia, and ductal carcinoma in situ were detected
in 71.3, 10.9, and 6.2% of cases, respectively. CONCLUSIONS: FDS is an innovative
method for visualizing intraductal mammary lesions and allows accurate selection
of mammary ducts with suspicious lesions that require surgical removal in women
with PND.
PMID- 29938368
TI - A Community Needs Assessment of Urban Utah American Indians and Alaska Natives.
AB - The needs of Urban American Indian/Alaska Native (AI/AN) populations are often
not well understood. In order to inform programs and services, the Urban Indian
Center of Salt Lake (UIC-SL), in cooperation with researchers from the University
of Utah, undertook a community needs assessment of AI/AN living along Utah's
Wasatch Front. A 60-item questionnaire was developed to capture information about
health status, services used, unmet needs, and common sources of information
about AI/AN community events and activities. Study participants (n = 336) were a
convenience sample. Descriptive statistics, including mean, standard deviation,
percentage, and 95% confidence intervals, were calculated. The most common health
provider diagnosed medical conditions included hypertension, obesity, and
diabetes. The prevalence of violence, substance abuse, and mental health
conditions were also high among study participants and their families. Compared
to the general Utah population, study participants experienced disparities
relative to diabetes prevalence, cognitive and visual disabilities, and access to
health care. In addition to health care services, respondents indicated a need
for cultural, social, and educational programs. They also reported high levels of
technology use, suggesting a possible avenue for communicating with this
population. This community-based participatory research project provided rich
information about the unmet needs of this urban AI/AN population. The results
will be used to guide UIC-SL strategic planning, and a database created for this
project will be available for future data collection, allowing for comparison of
results between sites and over time.
PMID- 29938369
TI - Out-of-hours discharge from intensive care, in-hospital mortality and intensive
care readmission rates: a systematic review and meta-analysis.
AB - PURPOSE: Discharge from an intensive care unit (ICU) out of hours is common. We
undertook a systematic review and meta-analysis to explore the association
between time of discharge and mortality/ICU readmission. METHODS: We searched
Medline, Embase, Web of Knowledge, CINAHL, the Cochrane Library and OpenGrey to
June 2017. We included studies reporting in-hospital mortality and/or ICU
readmission rates by ICU discharge "out-of-hours" and "in-hours". Inclusion was
limited to patients aged >= 16 years discharged alive from a non-specialist ICU
to a lower level of hospital care. Studies restricted to specific diseases were
excluded. We assessed study quality using the Newcastle Ottowa Scale. We
extracted published data, summarising using a random-effects meta-analysis.
RESULTS: Our searches identified 1961 studies. We included unadjusted data from
1,191,178 patients from 18 cohort studies (presenting data from 1994 to 2014).
"Out of hours" had multiple definitions, beginning between 16:00 and 22:00 and
ending between 05:59 and 09:00. Patients discharged out of hours had higher in
hospital mortality [relative risk (95% CI) 1.39 (1.24, 1.57) p < 0.0001] and
readmission rates [1.30 (1.19, 1.42), p < 0.001] than patients discharged in
hours. Heterogeneity was high (I2 90.1% for mortality and 90.2% for readmission),
resulting from differences in effect size rather than the presence of an effect.
CONCLUSIONS: Out-of-hours discharge from an ICU is strongly associated with both
in-hospital death and ICU readmission. These effects persisted across all
definitions of "out of hours" and across healthcare systems in different
geographical locations. Whether these increases in mortality and readmission
result from patient differences, differences in care, or a combination remains
unclear.
PMID- 29938371
TI - Lab 4.0: SiLA or OPC UA.
PMID- 29938370
TI - Quantification of total dinutuximab concentrations in neuroblastoma patients with
liquid chromatography tandem mass spectrometry.
AB - Neuroblastoma is one of the most commonly found solid tumors in children. The
monoclonal antibody dinutuximab (DNX) targets the sialic acid-containing
glycosphingolipid GD2 expressed on almost all neuroblastoma tumor cells and
induces cell lysis. However, the expression of GD2 is not limited to tumor cells
only, but is also present on central nerve tissue and peripheral nerve cells
explaining dinutuximab toxicity. The most common adverse reactions are pain and
discomfort, which may lead to discontinuation of the treatment. Furthermore,
there is little to no data available on exposure and effect relationships of
dinutuximab. We, therefore, developed an easy method in order to quantify
dinutuximab levels in human plasma. Ammonium sulfate (AS) was used to precipitate
all immunoglobulins (IgGs) in human plasma. After centrifugation, supernatant
containing albumin was decanted and the precipitated IgG fraction was re
dissolved in a buffer containing 0.5% sodium dodecyl sulfate (SDS). Samples were
then reduced, alkylated, and digested with trypsin. Finally, a signature peptide
in complementarity determining region 1 of DNX heavy chain was quantified on LC
MS/MS using a stable isotopically labeled peptide as internal standard. AS
purification efficiently removed 97.5% of the albumin fraction in the supernatant
layer. The validation performed on DNX showed that within-run and between-run
coefficients of variation (CV) for lower limit of quantification (LLOQ) were 5.5
and 1.4%, respectively. The overall CVs for quality control (QC) low, QC med, and
QC high levels were < 5%. Linearity in the range 1-32 mg/L was excellent (r2 >
0.999). Selectivity, stability, and matrix effect were in concordance with EMA
guidelines. In conclusion, a method to quantify DNX in human plasma was
successfully developed. In addition, the high and robust process efficiency
enabled the utilization of a stable isotopically labeled (SIL) peptide instead of
SIL DNX, which was commercially unavailable. Graphical abstract.
PMID- 29938373
TI - Infanticide and American criminal justice (1980-2018).
AB - Maternal infanticide, or the murder of a child in the first year of life by its
mother, is a subject both compelling and repulsive. The victim is innocent, but
the perpetrator may be a victim too. In the USA, mentally ill women who commit
infanticide may receive long prison sentences or even the death penalty. England,
Canada, Australia, and more than 20 European countries have "infanticide laws,"
which provide more humane treatment and psychiatric care for mentally ill mothers
who kill. One of the reasons for the sentences in the USA lies in our archaic
insanity defense. In addition, the psychiatric community does not recognize
perinatal illness as a formal diagnosis. Furthermore, general forensic
psychiatrists who testify in the courtroom have little knowledge of perinatal
illness. I suggest that it is time to invite psychiatrists and psychologists as
clinicians and scientists to partner with our legal representatives in the
courtroom in order to determine laws based on psychiatric facts and not
conjecture. The voices of perinatal mental health advocates must continue to be
heard in all courtrooms of the USA.
PMID- 29938372
TI - Antifouling and ultrasensitive biosensing interface based on self-assembled
peptide and aptamer on macroporous gold for electrochemical detection of
immunoglobulin E in serum.
AB - Accurate detection of protein biomarkers in complex media remains a challenge due
to severe nonspecific adsorption and biofouling, and sensing interfaces that
combine the high sensitivity and antifouling ability are highly desirable.
Herein, an antifouling sensing interface capable of sensitively assaying
immunoglobulin E (IgE) in biological samples was constructed. The sensing
interface was fabricated through the self-assembly of a zwitterionic peptide and
the IgE aptamer onto a macroporous Au substrate, which was electrochemically
fabricated with the aid of multilayer polystyrene nanospheres self-assembled on
glassy carbon electrode. Due to the huge surface area arising from porous
morphology and high specificity of aptamer, the developed electrochemical
biosensor exhibits ultrahigh sensitivity and selectivity towards IgE, with the
linear range of 0.1-10 pg mL-1, and a very low limit of detection down to 42 fg
mL-1. Interestingly, owing to the presence of the zwitterionic peptide, the
biosensing interface can satisfyingly reduce the nonspecific adsorption and
fouling effect. Consequently, the biosensor was successfully applied to detect
IgE in complex biological samples, indicating great promise of this peptide-based
sensing interface for antifouling assays. Graphical abstract ?.
PMID- 29938375
TI - Reply to: Relationship between LAT1 expression and resistance to chemotherapy in
pancreatic ductal adenocarcinoma.
PMID- 29938374
TI - Greenhouse gas emissions and energy exchange in wet and dry season rice: eddy
covariance-based approach.
AB - Lowland tropical rice-rice system has a unique micrometrological characteristic
that affects both energy component and net ecosystem energy. Periodic and
seasonal variations of methane (CH4), carbon dioxide (CO2), and energy exchange
from irrigated lowland rice-rice ecosystem were studied using open-path eddy
covariance (EC) system during the dry (DS) and wet (WS) seasons in 2015.
Concurrently, the manual chamber method was employed in nitrous oxide (N2O)
measurement efflux. Cumulative net ecosystem carbon exchange (NEE) was observed
highest (- 232.55 g C m-2) during the WS and lowest (- 14.81 g C m-2) during wet
fallow (WF). Similarly, the cumulative net ecosystem methane exchange (NEME) was
found highest (13,456.5 mg CH4 m-2) during the WS and lowest (2014.3 mg CH4 m-2)
during the WF. Surface energy fluxes, i.e., sensible (Hs) and latent heat (LE)
fluxes, showed a similar trend. With the advancement of time, the ratio of
ecosystem respiration (Re) and gross primary production (GPP) increased. The
cumulative global warming potential (GWP) for the two cropping seasons including
two fallows was 13,224.1 kg CO2 equivalent ha-1. The GWP and NEME showed a
similar trend as soil enzymes and labile carbon pools in both seasons (except GWP
at the harvesting stage in the wet season). The mean NEE exhibited a more
negative value with decrease in labile pools from panicle initiation to
harvesting stage in the WS. Soil labile C and soil enzymes can be used as an
indicator of NEE, NEME, and GWP in lowland rice ecology. Graphical abstract
Schematic presentation of GHG emission and energy exchange in lowland rice.
PMID- 29938376
TI - Natural infection in Pampas fox (Lycalopex gymnocercus) by Lagochilascaris major
Leiper, 1910 (Nematoda: Ascarididae) in Buenos Aires, Argentina.
AB - Lagochilascariosis is an emerging parasitic disease limited to the American
continent, caused by nematodes of the genus Lagochilascaris. Its life cycle is
heteroxenous, involving natural definitive hosts (wild carnivores), accidental
hosts (domestic carnivores and humans), and intermediate hosts (rodents). Here we
report, for the first time, the occurrence of Lagochilascaris major in female of
a Pampas fox (Lycalopex gymnocercus) which was found in the Mar Chiquita basin,
Buenos Aires province, Argentina. At necropsy, multiple Lagochilascaris larvae
and several adults (1 female and 5 male) were observed inserted in the mucosa of
the trachea and a male was also collected in the stomach. The diagnosis was made
by observing the different stages with optical microscopy, by scanning electron
microscopy of adult males and coproparasitological analysis. Although cases of
lagochilascariosis have been reported in wildlife in different countries of the
American continent, in Argentina, cases are really rare and were only found in
domestic cats. Graphical abstract ?Lagochilascariosis is an emerging parasitic
disease limited to the American continent. In Argentina, sporadic cases of
Lagochilascariosis were reported in domestic cats but this work represents the
first record in a wild carnivore (L. gymnocercus) naturally infected with L.
major.
PMID- 29938377
TI - Halal slaughtering, welfare, and empathy in farm animals: a review.
AB - Pre-slaughter and slaughter stressors are considered major concerns in animal
welfare. Halal slaughtering method is considered one of the slaughtering
stressors in livestock. This method seems to cause fear followed by stress in
animals mainly due to inhuman handling. In this review, empathy and animal
welfare are discussed in light of Islamic sharia and has further linked with
animal's physiology and behavioral responses during slaughtering. Islam as a
religion forbids slaughtering an animal in front of another animal as through
optic, olfactory, and cochlear senses animals can perceive the stress state of
conspecifics. This suggests and strengthens the hypothesis that animals being
slaughtered in front of each other may produce stress in them. This argument
further leads to a claim that animals can experience empathy of each other
through olfaction of semiochemicals (stress pheromones) emitted from animals
slaughtered in the stressful condition that can be detected by other animals in
abattoirs. Hence, research is needed to find out these specific stress pheromones
and legislation needs to be adopted in slaughterhouses to isolate the areas of
butchery from slaughtering lines to ensure proper guidelines of Halal
slaughtering in slaughterhouses.
PMID- 29938378
TI - Hydrogen peroxide-induced oxidative stress and its impact on innate immune
responses in lung carcinoma A549 cells.
AB - The immune responses, involved in recognition of cancer-specific antigens, are of
particular interest as this may provide major leads towards developing new
vaccines and antibody therapies against cancer. An effective treatment for cancer
is still a challenge because there are many mechanisms through which the tumor
cells can escape the host immune surveillance. Oxidative stress or respiratory
burst which is host's mechanism to kill the foreign particles is used as defense
mechanism by the tumor cells. The tumor cells uses this oxidative stress to form
neo-antigens which in turn makes them undetectable and can escape the host immune
surveillance. The human lung carcinoma (A549) cells were treated using 100 uM
H2O2 to induce oxidative stress, and the extent oxidative modifications were
detected at the level of membrane and proteins in form of lipid peroxidation and
protein carbonyls respectively. Nitric oxide and iNOS levels were estimated by
Griess assay and immunostaining, respectively. The oxidized tumor proteins were
visualized on one-dimensional SDS-PAGE. The H2O2-treated (15 min and 24 h post
treatment) A549 cells were co-cultured with THP-1 cells to subsequently visualize
the phagocytic activity by Giemsa and CFSE staining to understand the role of neo
(oxidized) tumor antigens in eliciting alteration in immune responses. A
significant decline in the percent engulfed cells and decrease in the levels of
reactive oxygen species was observed. Immunohistostaining for p47phox, which is
an important indicator of the oxygen-dependent phagocytosis, showed a decrease in
its levels when cells were treated for only 15 min with 100 uM H2O2, whereas at
24-h post-treatment there was no change in the p47phox levels. The study has
established oxidative stress as a new pathogenic mechanism of carcinogenesis and
will open new avenues for clinical intervention, adjunct therapies for cancer,
and its control at the initial stage by targeting these neo-antigens.
PMID- 29938379
TI - An Augmented Reality Endoscope System for Ureter Position Detection.
AB - Iatrogenic injury of ureter in the clinical operation may cause the serious
complication and kidney damage. To avoid such a medical accident, it is necessary
to provide the ureter position information to the doctor. For the detection of
ureter position, an ureter position detection and display system with the
augmented ris proposed to detect the ureter that is covered by human tissue.
There are two key issues which should be considered in this new system. One is
how to detect the covered ureter that cannot be captured by the electronic
endoscope and the other is how to display the ureter position that provides
stable and high-quality images. Simultaneously, any delayed processing of the
system should disturb the surgery. The aided hardware detection method and target
detection algorithms are proposed in this system. To mark the ureter position, a
surface-lighting plastic optical fiber (POF) with the encoded light-emitting
diode (LED) light is used to indicate the ureter position. The monochrome channel
filtering algorithm (MCFA) is proposed to locate the ureter region more
precisely. The ureter position is extracted using the proposed automatic region
growing algorithm (ARGA) that utilizes the statistical information of the
monochrome channel for the selection of growing seed point. In addition,
according to the pulse signal of encoded light, the recognition of bright and
dark frames based on the aided hardware (BDAH) is proposed to expedite the
processing speed. Experimental results demonstrate that the proposed endoscope
system can identify 92.04% ureter region in average.
PMID- 29938380
TI - Dental pulp stem cells and osteogenesis: an update.
AB - Dental pulp stem cells constitute an attractive source of multipotent mesenchymal
stem cells owing to their high proliferation rate and multilineage
differentiation potential. Osteogenesis is initiated by osteoblasts, which
originate from mesenchymal stem cells. These cells express specific surface
antigens that disappear gradually during osteodifferentiation. In parallel, the
appearance of characteristic markers, including alkaline phosphatase, collagen
type I, osteocalcin and osteopontin characterize the osteoblastic phenotype of
dental pulp stem cells. This review will shed the light on the osteogenic
differentiation potential of dental pulp stem cells and explore the culture
medium components, and markers associated with osteodifferentiation of these
cells.
PMID- 29938381
TI - Critical analysis and mapping of research trends and impact assessment of
polyaromatic hydrocarbon accumulation in leaves: let history tell the future.
AB - The article is basically an attempt to provide a consolidated report on impact
assessment and trends in research pertaining to accumulation and curbing the
menace of polyaromatic hydrocarbon (PAH) accumulation in leaves. Emphasis is
given to understand the consequences of the fact that edible/medicinal plants
cultivated in PAH contaminated soil or close to such places which are potential
liberators of PAHs can virtually act as transporters for direct PAH entry into
biological systems. An attempt has been made to predict the future by digging out
golden facts from history. Extensive Scopus-based data mining has been done to
dig out research data since last 10 years (2006-2016) pertaining to the said
area. Critical analysis of statistical data on research trends highlighting the
different aspects of evaluation of PAH accumulation in leaves has been described.
The concentrate of all researches for the said period have been presented as few
golden principles which shall serve as important facts for researchers and policy
makers for curbing the menace of PAH-induced oxidative stress in plants and shall
also provide start-up ideas for researchers new to the area. Critical analysis of
trends in phytoremediation aspect has also been duly highlighted to measure the
intensity of restoration steps taken by researchers and government to safeguard
the future generations.
PMID- 29938382
TI - Mitigation of NOx and smoke emissions in a diesel engine using novel emulsified
lemon peel oil biofuel.
AB - Lemon peel oil (LPO) is considered to be a viable alternative fuel for diesel
engine applications due to its wider availability, renewable nature, easy
extraction process, almost equivalent calorific value as neat diesel, and low
viscosity. The present work aims to investigate the effect of novel emulsified
LPO in a diesel engine in order to reduce the NOx emission without compromising
the engine performance. A new ionic surfactant is introduced in the present
study, namely methyl-dihydroxy propyl imidazolium chloride due to its higher
hydrophilic-lipophilic balance value which helps to prepare stable water in oil
emulsion. Also, Span 80 has been selected as another suitable surfactant for
water in oil emulsion. Four emulsified fuel samples have been prepared using LPO,
water, and different concentrations of surfactants. All the fuel samples are
tested for their stability through gravitational technique for 7 days. Among the
emulsified samples, 92% LPO + 5% water + 2% Span 80 + 1% methyl-dihydroxy propyl
imidazolium chloride by volume (LPOE2) and 93.5% LPO + 5% water + 1.5% surfactant
Span 80 by volume (LPOE4) have showed better stability when compared to other
emulsion fuel samples. It is also revealed that the stability of LPO emulsion is
improved by the addition of two emulsions. The experimental results showed that
the brake thermal efficiency of LPO emulsion is reduced to 29.87 from 34.58% of
pure LPO at full load condition. Oxides of nitrogen emission and smoke emission
are reduced by 21-32 and 6-15% for the LPO emulsion samples compared to pure LPO.
Moreover, the diesel engine operation with emulsified form of LPO increases the
HC emission about 0.1 g/kWh for LPOE4 and 0.15 g/kWh for LPOE2 fuels from 0.053
g/kW for pure LPO at maximum power output condition. The reformulation of LPO
into emulsified form increases the CO emission by 25-53% compared to pure LPO.
Moreover, the reformulation of LPO into emulsions has resulted in lower cylinder
pressure and heat release rate compared to pure LPO and diesel fuels.
PMID- 29938383
TI - Planning for agricultural return flow allocation: application of info-gap
decision theory and a nonlinear CVaR-based optimization model.
AB - A new methodology is proposed for sizing the required infrastructures for water
and waste load allocation in river systems receiving return flow from
agricultural networks. A nonlinear optimization model with a constraint based on
conditional value at risk (CVaR) is developed to provide water and waste load
allocation policies. The CVaR-based constraint limits the probabilistic losses
due to existing uncertainties in available surface water. The deep uncertainties
of return flow simulation model parameters, which have significant impacts on the
simulated quantity and quality of agricultural return flows, are handled by using
the info-gap theory. Total dissolved solid (TDS) is selected as water quality
indicator and diverting a fraction of return flows to evaporation ponds is
considered to control the TDS load of agricultural waste load dischargers.
Quantity and TDS load of agricultural return flows over a 1-year cultivation
period are simulated by using a calibrated SWAP agro-hydrological model. The
results of many runs of SWAP model for different combinations of important
uncertain parameters in their ranges of variations provide some response (impact)
matrixes which are used in optimization model. The applicability of the proposed
methodology is illustrated by applying it to the PayePol region in the Karkheh
River catchment, southwest Iran. The selected strategy for water and waste load
allocation in the study area is expected to provide total annual benefit of 48.64
million US dollars, while 7.84 million m3 of total return flow should be diverted
to evaporation ponds. The results support the effectiveness of the methodology in
incorporating existing deep uncertainties associated with agricultural water and
waste load allocation problems.
PMID- 29938384
TI - Smoking Is Positively Associated with Antithyroperoxidase Antibodies and
Antithyroglobulin Antibodies in Populations with Mildly Deficient Iodine Intake.
AB - To evaluate the relationship between smoking and both antithyroperoxidase
antibody (TPOAb) and antithyroglobulin antibody (TgAb) positivity in subjects
from Panshan, Zhangwu, and Huanghua with mildly deficient, more than adequate,
and excessive iodine intake, respectively. Smoking-related data were collected by
questionnaire, and laboratory measurements of TPOAb, TgAb, and thyrotropin (TSH)
were determined at baseline and follow-up. (1) A 1.48-fold increased risk of
TPOAb positivity was found in smokers than in non-smokers after adjusting for
confounders (age, sex, and areas) (OR[95% CI] = 1.48[1.12-1.95], p = 0.01). (2)
Among female subjects, the prevalence of thyroid autoantibodies in smokers was
increased than that in non-smokers in Panshan, Zhangwu, and Huanghua (TPOAb):
16.79 vs. 8.89%, 14.14 vs. 11.09%, 19.53 vs. 9.57%; TgAb 15.32 vs. 9.29%, 12.79
vs. 11.94%, 17.19 vs. 10.55%, respectively). The difference was significant in
Panshan after adjusting for age. (3) Female long-term smokers (> 20 years) had an
increased frequency of thyroid autoantibody positivity than non-smokers after
adjusting for confounders (TPOAb OR[95% CI] = 1.60[1.10-2.34]; TgAb OR[95% CI] =
1.31[0.88-1.94]). (4) There was no difference in the incidence of thyroid
autoantibodies among non-smokers, new smokers, and long-term smokers at follow
up. (5) TSH was greater in TPOAb-positive subjects than in seronegative smokers
(1.56 vs. 1.20 mU/L, p < 0.001) and non-smokers (1.97 vs. 1.58 mU/L, p < 0.001).
However, TSH was also greater in non-smokers than in smokers, regardless of
whether subjects were positive (1.97 vs. 1.56 mU/L, p = 0.04) or negative (1.58
vs. 1.20 mU/L, p < 0.001) for TPOAb. Long-term smoking could increase the
prevalence of thyroid autoantibodies in a population with mildly deficient iodine
intake. TSH levels were lesser in smokers than in non-smokers and greater in
subjects with thyroid autoantibody positivity than in seronegative subjects. The
influence of smoking on TSH levels was independent of thyroid autoantibody
levels.
PMID- 29938385
TI - Past, present or future? Word tense and affect in autobiographical narratives of
women with HIV in relation to health indicators.
AB - This study examined how the expression of positive and negative affect words and
word tense in autobiographical narratives of 98 HIV+ women, predominantly African
American, predicted undetectable HIV viral load (UDVL), CD4+ cells/mm3 counts and
antiretroviral therapy medication (ART) adherence assessed concurrently (T1) and
at 3 to 9-month follow-up (T2). Logistic regressions revealed that higher past
tense words predicted worse odds of UDVL, CD4+ cells/mm3 above 350 at T1, and
worse odds of 95% ART adherence at T2. However, using both high past tense words
and high positive affect words predicted better odds of CD4+ cells/mm3 > 350 at
T2. Higher future tense words predicted better odds of CD4+ cells/mm3 > 350 at
T1. Additionally, using both high present tense words and negative affect words
predicted better odds of UDVL at T1. These findings provide preliminary evidence
that the quality of affect expression significantly interacts with temporal
context to relate to the health of women with HIV.
PMID- 29938386
TI - Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth.
AB - Axonal outgrowth and guidance require numerous extracellular cues and
intracellular mediators that transduce signals in the growth cone to regulate
cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond
to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron
expressed RhoGTPase-activating protein, plays an essential role in the inhibition
of initial axon growth by restricting the expansion of the growth cone in a cell
autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream
controller that binds and regulates Porf-2 specifically upon extracellular ephrin
B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP
domain of Porf-2, which inhibits growth cone formation and brakes axon growth.
Our results therefore provide a novel GAP that regulates axon growth and braking
sequentially through Eph receptor-independent and Eph receptor-dependent
pathways.
PMID- 29938388
TI - Crime scene and body alterations caused by arthropods: implications in death
investigation.
AB - The activity of arthropods on corpses has been largely investigated, since they
can produce information to reconstruct the peri-mortem events. However, the
feeding/movement activity of insects around the crime scene, among the clothes
and on the body, can also cause some alterations that can lead to wrong
reconstruction and misinterpretations. This article summarises all the post
mortem arthropods artefacts related to the scene (i.e. fly artefacts and floor
stripes) and the body (i.e. skin and other soft tissue alterations, bone
alterations and hair alterations) that can mislead the forensic pathologist,
discussing macroscopic and microscopic findings derived from forensic casework
and from experimental laboratory studies, in order to provide a useful instrument
to avoid misinterpretations and evaluation errors. Finally, some procedural notes
for the documentation and the interpretation of findings are proposed.
PMID- 29938387
TI - Myotoxicity of local anesthetics is equivalent in individuals with and without
predisposition to malignant hyperthermia.
AB - PURPOSE: Malignant hyperthermia (MH) is an inherited muscle disorder caused by
abnormal elevations of intracellular calcium (Ca2+) in skeletal muscle. There are
several reports of myotoxicity caused by local anesthetics, and the increased
intracellular Ca2+ is considered to be an important cause. However, there is
insufficient evidence regarding myotoxicity in MH-susceptible individuals when
large doses of local anesthetics are administered. This study investigated the
effect of MH predisposition on myotoxicity. METHODS: Human skeletal muscle
samples were obtained from 22 individuals to determine susceptibility to MH, and
were evaluated according to whether their Ca2+-induced Ca2+ release (CICR) rates
were accelerated or not. This study was performed using surplus muscle that
remained after the CICR rate test. We calculated the 50% effective concentration
(EC50) values of three local anesthetics, namely lidocaine, levobupivacaine, and
ropivacaine using the ratiometric dye Fura-2 AM. Significance was tested using
the unpaired t test. RESULTS: In the accelerated and unaccelerated groups,
respectively, the mean +/- SD of the EC50 values were 1.52 +/- 0.72 and 1.75 +/-
0.37 mM for lidocaine (p = 0.42), 0.72 +/- 0.36 and 0.79 +/- 0.46 mM for
levobupivacaine (p = 0.68), and 1.21 +/- 0.35 and 1.62 +/- 0.57 mM for
ropivacaine (p = 0.06). These values were similar in individuals with and without
MH predisposition. CONCLUSION: The myotoxicity of local anesthetics was
equivalent in individuals with and without predisposition to MH.
PMID- 29938389
TI - A BODIPY Based Fluorescent Probe for the Rapid Detection of Hypochlorite.
AB - A new boron-dipyrromethene (BODIPY) fluorescent dye aimed at sensitively
detecting hypochlorite anion (ClO-) has been designed, synthesized and
characterized. The probe is comprised of a BODIPY fluorophore unit and a ClO-
specific reactive group of amidoxime. The addition of hypochlorite results in a
red-shift of absorption and emission spectra of the probe accompanied by a
decrease of intensity and spectra changes (A500 and 1/I512) of the probe can
achieve a good linearity to the concentration of ClO-. The fluorescence probe can
react to ClO- rapidly (within 60 s) in a wide pH range (4-10) with high
sensitivity (detection limit of 6.81 MUM) and selectivity. The reaction mechanism
has been proposed and confirmed by MS analysis, ClO- anion oxidizes amidoxime
moiety to hydroxyl group and hydroxyl group is further oxidized to formyl group
in the formation of a corresponding aldehyde compound. In addition, the probe has
also been successfully applied to detect ClO- in tap water and river water
samples by spiking a known amount of standard ClO-.
PMID- 29938390
TI - Two Photon Spectroscopy Can Serve as a Marker of Protein Denaturation Pathway.
AB - Rhodamine group of molecules are widely used dyes for imaging of biological
molecules. Application of these dyes however includes a limitation that these
molecules absorb in the visible range of the spectrum, which does not fall in the
'biologically transparent window' (BTW). Two photon absorption (TPA) process
could come up with an alternate solution to this as these dyes could be excited
in the near infrared (NIR) window to extract similar information. To validate
this we have investigated TPA cross section (TPACS, sigma2) of two rhodamine
dyes, namely Rhodamine 6G (R6G), Rhodamine B (RhB), site selectively bound with a
model protein, bovine serum albumin (BSA), by exciting at 800 nm. Two photon
spectroscopy and imaging confirms the binding of the dye to the protein. The
decreases in TPACS with increasing temperature at a fixed BSA concentration
excellently follows the temperature induced structural transition of BSA as the
protein transforms from a molten globule to unfolded conformation beyond 60
degrees C, which has previously been established through circular dichroism (CD)
measurements. The thus established resemblance in TPACS and CD measurement trends
thus strongly affirms the suitability of TPA process in protein imaging and as an
alternative marker to tracking its conformational transformations using NIR
radiation.
PMID- 29938391
TI - Left ventricular assist device implantation after plasma exchange for heparin
induced thrombocytopenia.
AB - Treating a patient with heparin-induced thrombocytopenia can be challenging
particularly when the patient requires urgent cardiac surgery that uses heparin
for anticoagulation. We herein report a case of a 61-year-old man with idiopathic
dilated cardiomyopathy associated with heparin-induced thrombocytopenia and who
underwent plasma exchange to remove heparin-induced thrombocytopenia antibodies
before undergoing left ventricular assist device implantation. The surgery was
performed using cardiopulmonary bypass and unfractionated heparin.
PMID- 29938392
TI - Efficacy of regional saturation of oxygen monitor using near-infrared
spectroscopy for lower limb ischemia during minimally invasive cardiac surgery.
AB - Lower limb ischemia with an occlusive cannula is a potential complication of
minimally invasive cardiac surgery (MICS). We evaluated intraoperative local
oxygen supply-demand balance by monitoring regional saturation of oxygen (rSO2)
using near-infrared spectroscopy (NIRS), and analyzed the correlation between
cannula size and fluctuation range of rSO2. Fifty-four patients undergoing MICS
surgery using femoral artery cannulation from April 2015 to August 2016 were
enrolled. The rSO2 of both the cannulated and uncannulated lower limbs were
measured using NIRS. The association between the decline of rSO2 from baseline
(delta-rSO2) and the ratio of the cannula diameter to the femoral artery diameter
(Cd/FAd) was analyzed. Of the 54 patients, 16 (30%) (Group 1) showed values over
0.65 for Cd/FAd, and the remaining 38 (70%) (Group 2) showed values under 0.65.
No patient developed postoperative lower limb ischemia. No patient was treated
with an ipsilateral distal perfusion cannula. There were significant differences
between Group 1 and Group 2 in the decrease of rSO2 at the point of cannulation
on the cannulated limb. In the lower limb on the cannulated side, delta-rSO2
showed a significant decrease in Group 1 compared to Group 2 (Group 1 vs Group 2:
19.9 vs 11.0%; p < 0.001). Delta-rSO2 was significantly correlated with body
surface aera (BSA), but not with gender or age. Decreasing rSO2 correlates with
the Cd/FAd index. Low BSA, Cd/Fad > 0.65 is considered as the risk factor for
decline of rSO2 in cannulated limb in MICS.
PMID- 29938394
TI - Neuroendocrine tumor of the pancreas with rhabdoid feature.
AB - Imaging of a 53-year-old Japanese man revealed two tumors in the liver and a
tumor in the head of the pancreas with a swelling lymph node. A needle biopsy for
the liver tumors was performed, revealing a neuroendocrine tumor. Enucleation,
lymphadenectomy, and partial hepatectomy were performed. The microscopic
examination identified many tumor cells with intracytoplasmic inclusions arranged
in a nested, cord, or tubular fashion. The intracytoplasmic inclusions displayed
densely eosinophilic globules and displaced the nuclei toward the periphery,
which constitutes "rhabdoid" features. The tumor cells were positive for
synaptophysin and weakly positive for NCAM, but negative for chromogranin A.
Epithelial markers (AE1/AE3 and CAM5.2) accentuated intracytoplasmic globules.
Pancreatic neuroendocrine tumors with rhabdoid features are very rare. Generally,
rhabdoid features are aggressive and dedifferentiated characteristics of various
types of tumor. Pancreatic neuroendocrine tumors containing rhabdoid cells tend
to display extrapancreatic spread at the time of presentation, although some of
these tumors with rhabdoid features are not always associated with aggressive
behavior.
PMID- 29938393
TI - Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and
rs2853669 with diabetes mellitus in obese elderly Polish population: results from
the national PolSenior study.
AB - One of the markers of aging is lymphocyte telomere length (LTL), which is
affected by genetic constitution of the organism and environmental conditions,
such as development and diseases, including diabetes. The relationship of the
later seems to be bilateral. The enzyme responsible for the maintenance of
telomere length is a subunit of telomerase-telomerase reverse transcriptase
(TERT). The aims of the present study were to (1) determine the influence of the
TERT promoter sequence SNP variants on relative telomere length (RTL) in an
elderly Polish population and (2) explore the potential associations of the SNPs
with the type 2 diabetes mellitus (T2DM) in the obese individuals. Two highly
homogenous subgroups of PolSenior participants were investigated, the first
constituted 70 relatively healthy respondents and the second 70 individuals with
T2DM. Telomere length ratio (T/S value) was measured; 1.5 kb part upstream of the
transcription start site of the TERT promoter was sequenced, and the frequencies
of polymorphisms were calculated and compared against analysed data. Low
frequency SNPs were evaluated but excluded from further comparative analyses to
RTL and glucose metabolism markers. No significant difference in telomere length
was found between the two studied subgroups. Univariate statistical analyses
showed only a weak association of environmental or genetic factors altering this
marker of aging. Approximate frequency of four SNPs in TERT promoter sequence was
assessed in Polish population aged 65-95 years, but three of them (rs2735940,
rs7712562 and rs2853669) were selected for further analyses. The SNP selection
was based on their minor allele frequencies in general population and on
published data. The univariate analysis has revealed that carriers of CC SNP
(rs2853669) have had the shortest RTL in the T2DM group. Multivariate analysis
has also revealed that the genetic effect of TERT promoter CC SNP was
strengthened by the incidence of T2DM. The additional variation in RTL in paired
groups indicates that in addition to T2DM and genetics, there are other factors
contributing to development of the age-related diseases.
PMID- 29938395
TI - LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat
progressive HER2-positive breast cancer brain metastases.
AB - PURPOSE: HER2 + breast cancer (BC) is an aggressive subtype with high rates of
brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the
PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study
evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and
vinorelbine (V) in patients with HER2 + BCBM. PATIENTS AND METHODS: Eligible
patients had progressive HER2 + BCBM. The primary endpoint was intracranial
response rate (RR); secondary objectives were CNS clinical benefit rate (CBR),
extracranial RR, time to progression (TTP), overall survival (OS), and targeted
sequencing of tumors from enrolled patients. A two-stage design distinguished
intracranial RR of 5% versus 20%. RESULTS: 32 patients were evaluable for
toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was
27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2-5). OS was
12.2 mos (95% CI 0.6-20.2). Grade 3-4 toxicities included neutropenia (41%),
anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in
BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2
amplification was higher in BCBM compared to primary BC; ERBB2 amplification in
the primary BC trended toward worse OS. CONCLUSION: While intracranial RR to ETV
was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar
to historical control. No new toxicity signals were observed. Further analysis of
the genomic underpinnings of BCBM to identify tractable prognostic and/or
predictive biomarkers is warranted. CLINICAL TRIAL: (NCT01305941).
PMID- 29938396
TI - PET imaging for assessing tumor response to therapy.
AB - Positron emission tomography (PET) is a radioisotope imaging technique capable of
quantifying the regional distribution of molecular imaging probes targeted to
biochemical pathways and processes allowing direct measurement of biochemical
changes induced by cancer therapy, including the activity of targeted growth
pathways and cellular populations. In this manuscript, we review the underlying
principles of PET imaging, choices for PET radiopharmaceuticals, methods for
tumor analysis and PET applications for cancer therapy response assessment
including potential future directions.
PMID- 29938397
TI - Carbon stocks, sequestration, and emissions of wetlands in south eastern
Australia.
AB - Nontidal wetlands are estimated to contribute significantly to the soil carbon
pool across the globe. However, our understanding of the occurrence and
variability of carbon storage between wetland types and across regions represents
a major impediment to the ability of nations to include wetlands in greenhouse
gas inventories and carbon offset initiatives. We performed a large-scale survey
of nontidal wetland soil carbon stocks and accretion rates from the state of
Victoria in south-eastern Australia-a region spanning 237,000 km2 and containing
>35,000 temperate, alpine, and semi-arid wetlands. From an analysis of >1,600
samples across 103 wetlands, we found that alpine wetlands had the highest carbon
stocks (290 +/- 180 Mg Corg ha-1 ), while permanent open freshwater wetlands and
saline wetlands had the lowest carbon stocks (110 +/- 120 and 60 +/- 50 Mg Corg
ha-1 , respectively). Permanent open freshwater sites sequestered on average
three times more carbon per year over the last century than shallow freshwater
marshes (2.50 +/- 0.44 and 0.79 +/- 0.45 Mg Corg ha-1 year-1 , respectively).
Using this data, we estimate that wetlands in Victoria have a soil carbon stock
in the upper 1 m of 68 million tons of Corg , with an annual soil carbon
sequestration rate of 3 million tons of CO2 eq. year-1 -equivalent to the annual
emissions of about 3% of the state's population. Since European settlement
(~1834), drainage and loss of 260,530 ha of wetlands may have released between 20
and 75 million tons CO2 equivalents (based on 27%-90% of soil carbon converted to
CO2 ). Overall, we show that despite substantial spatial variability within
wetland types, some wetland types differ in their carbon stocks and sequestration
rates. The duration of water inundation, plant community composition, and
allochthonous carbon inputs likely play an important role in influencing
variation in carbon storage.
PMID- 29938399
TI - Corrigendum.
PMID- 29938398
TI - Perceptions of future health and cancer risk in adult survivors of childhood
cancer: A report from the Childhood Cancer Survivor Study.
AB - BACKGROUND: Survivors of childhood cancer are at significant risk for serious
chronic health conditions and subsequent cancers because of their prior treatment
exposures. However, little is known about survivors' perceptions of their future
health risks. METHODS: This study examined self-reported levels of concern about
future health and subsequent cancer in 15,620 adult survivors of childhood cancer
(median age, 26 years; median time since diagnosis, 17 years) and 3991 siblings
in the Childhood Cancer Survivor Study. The prevalence of concerns was compared
between survivors and siblings, and the impact of participant characteristics and
treatment exposures on concerns was examined with multivariable modified Poisson
regression to estimate relative risks (RRs) and 95% confidence intervals (CIs).
RESULTS: A substantial proportion of survivors were not concerned about their
future health (31%) or developing cancer (40%). The prevalence of concern in
survivors was modestly higher (RR for future health, 1.12; 95% CI, 1.09-1.15) or
similar (RR for subsequent cancer, 1.02; 95% CI, 0.99-1.05) in comparison with
siblings. Survivors exposed to high doses of radiation (>=20 Gy) were more likely
to report concern (RR for future health, 1.13; 95% CI, 1.09-1.16; RR for
subsequent cancer, 1.14; 95% CI, 1.10-1.18), but 35% of these high-risk survivors
were not concerned about developing cancer, and 24% were not concerned about
their future health. CONCLUSIONS: A substantial subgroup of survivors were
unconcerned about their future health and subsequent cancer risks, even after
exposure to treatments associated with increased risk. These survivors may be
less likely to engage in beneficial screening and risk-reduction activities.
Cancer 2018. (c) 2018 American Cancer Society.
PMID- 29938402
TI - Hidden Risks behind Normal Fasting Glucose: Is It Significant?
PMID- 29938400
TI - Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal
origin: A narrative review.
AB - Patients with peritoneal carcinomatosis (PC) from colorectal origin may undergo
cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy
(HIPEC) as a curative approach. One major prognostic factor that affects survival
is completeness of cytoreduction. Molecular Fluorescence Guided Surgery (MFGS) is
a novel intraoperative imaging technique that may improve tumor identification in
the future, potentially preventing over- and under-treatment in these patients.
This narrative review outlines a chronological overview of MFGS development in
patients with PC of colorectal origin.
PMID- 29938403
TI - Letter: Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes
between 2015 and 2016: Difference by Age and Body Mass Index (Diabetes Metab J
2018;42:137-46).
PMID- 29938404
TI - Response: Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes
between 2015 and 2016: Difference by Age and Body Mass Index (Diabetes Metab J
2018;42:137-46).
PMID- 29938405
TI - Corrigendum: Hemorheologic Alterations in Patients with Type 2 Diabetes Mellitus
Presented with an Acute Myocardial Infarction.
AB - This corrects the article on p. 155 in vol. 42, PMID: 29676545.
PMID- 29938406
TI - The Role of Optical Coherence Tomography in the Acute Management of Neuro
Ophthalmic Diseases.
AB - Optical coherence tomography (OCT) can provide high-speed and high-resolution
images of the anatomical structures of the optic nerve head and macula. However,
in neuro-ophthalmic conditions that present acutely, structural changes lag
functional deficits, and the role of OCT in the acute setting has been
challenged. This review aims to summarize the recent literature and evidence
supporting the use of OCT in the acute management of some common neuro-ophthalmic
scenarios, including the differential diagnosis of optic disc swelling, and in
patients with suspected papilledema, optic neuritis, ischemic optic neuropathies,
and Leber hereditary optic neuropathy. The limitations of OCT are also discussed.
PMID- 29938401
TI - A practical guide for the use of indocyanine green and methylene blue in
fluorescence-guided abdominal surgery.
AB - Near-infrared (NIR) fluorescence imaging is gaining clinical acceptance over the
last years and has been used for detection of lymph nodes, several tumor types,
vital structures and tissue perfusion. This review focuses on NIR fluorescence
imaging with indocyanine green and methylene blue for different clinical
applications in abdominal surgery with an emphasis on oncology, based on a
systematic literature search. Furthermore, practical information on doses,
injection times, and intraoperative use are provided.
PMID- 29938407
TI - TRACKING SGDS: Importance Of Disease Registries And Burden Of Disease In
Pakistan.
PMID- 29938408
TI - Pre-Anaesthetic Assessment Of Intracranial Pressure Using Optic Nerve Sheath
Diameter In Patients Scheduled For Elective Tumour Craniotomy.
AB - Background: The objective of study was to determine the pre-anaesthetic status of
intracranial pressure (ICP), using ultrasonographic measurement of optic nerve
sheath diameter (ONSD) inpatient scheduled for elective tumour craniotomy. The
secondary objective was to compare the diagnostic accuracy of ONSD guided rise in
ICP with clinical and radiographic parameters. This is prospective observational
study, conducted at single neurosurgical theatre of The Aga Khan University over
a period of one year. Methods: After getting ethical approval and informed
consent patient fulfilling inclusion criteria and planned for elective tumour
craniotomy were enrolled in study. The clinical and radiographic signs predicting
the status of ICP were recorded. The ultrasonographic measurement of ONSD was
done using liner array probe. Value more than 5 mm was considered as abnormal.
Results: Total 26 cases were enrolled. Seventy percent patients showed rise in
ICP based on clinical parameters, while 65% diagnosed to have raised ICP on the
basis of radiographic findings. The ultrasonographic measurement of ONSD
predicted this rise in 61% of cases. The diagnostic accuracy of ONSD in detecting
raised ICP in comparison to clinical and radiographic evidence was 87.5%
respectively. Conclusions: The ultrasonographic-guided ONSD was used successfully
for predicting the status of ICP in pre-induction phase of anaesthesia. It also
showed good correlation in diagnosing rise in ICP as compared to clinical and
radiographic parameters, which indicates that test can be used reliably in
preoperative period for patients planned for tumour craniotomy.
PMID- 29938409
TI - Medial Sural Artery Perforator Flap: A Versatile Option For Soft Tissue
Reconstruction Of Head And Neck And Limbs.
AB - BACKGROUND: To assess the outcome of Medial Sural Artery Perforator Flap (MSAP
Flap) as an option for the soft tissue reconstruction of head and neck and limbs.
METHODS: This descriptive case series was conducted at Jinnah Burn and
Reconstructive Surgery Center, Lahore during October 2016 to August 2017. All
patients in whom MSAP flap (free and pedicled) was performed for reconstruction
are included. Patients were followed at one week and one month after the
discharge and data was entered into the proformas. RESULTS: In total, 18 patients
were operated with this flap. Free and pedicled MSAP flap were performed for
reconstruction of soft tissue defects in the head and neck and the lower limb.
The maximum dimensions of the flap were 14 cm length and 10 cm width. The maximum
pedicle length was 16cm. All flaps survived and showed good outcome. There was
necrosis of the distal margin of a pedicled flap, but no case of venous
congestion and flap failure was observed. The flap donor site was closed
primarily in 7 patients while split skin graft was used in the rest of the
patients. CONCLUSIONS: The MSAP flap provides a thin skin paddle and has minimal
donor site morbidity as compared to the other options. It is a good addition to
the armamentarium of perforator flaps which are thin and pliable, can be
harvested by two team approaches, under the tourniquet and has a hidden donor
site.
PMID- 29938410
TI - Histological Comparison Of Two Staining Methods In Identification Of
Mycobacterium Tuberculosis In Granulomatous Lymphadenitis.
AB - BACKGROUND: Tuberculosis, among human bacterial infections is very important
disease of modern world and disease has forensic importance. Extra pulmonary
infection is also very common. Histopathology of effected tissue is an important
diagnostic modality. Demonstration of mycobacterium tuberculosis in granulomas is
necessary for definitive diagnosis of tuberculosis, as many different
granulomatous diseases may mimic tuberculosis. Study was conducted to see the
positivity of mycobacterium Tuberculosis in tuberculous lymphadenitis and
comparative difference in two stains. METHODS: A correctional study on
tuberculosis was performed in PGMI Lahore in collaboration with pathology
department Ayub medical college Abbottabad. Fifty cases of formalin fixed
paraffin embedded tissue block previously diagnosed as tuberculous lymphadenitis
on histopathology were selected. Three-micron thick section were taken and
stained with Zn stain and Auramin/ Rhodamin stain. The results were compared;
statistical analysis was done using 2*2 table. RESULTS: Out of 33(66%) female and
17 (34%) male patients ranging from 9-80 years 9 (18%) were positive for
Mycobacterium Tuberculosis with Zn stain and 21 (42%) were positive in Auramine/
Rhodamine staining procedure. CONCLUSIONS: Auramine/ Rhodamine staining procedure
was superior to Zn staining method for tissue staining of Mycobacterium
Tuberculosis.
PMID- 29938411
TI - Comparison Of Frequency Of Post Operative Sensitivity In Amalgam Restorations
Using Copal Varnish And Dentin Adhesive Liner.
AB - BACKGROUND: Micro leakage around the margins of a restoration is believed to be
one of the main causes of postoperative sensitivity. Dental amalgam is a non
insulating material and has the potential to transfer heat and cold causing
irritation of the pulp. Different dentin tubule sealers are used under amalgam
restoration to compensate for this post-operative sensitivity. This study was
conducted to compare the frequency of sensitivity in amalgam restorations using
copal varnish and dentin adhesive liner (dentin bonding agent). METHODS: A total
of 60 patients of either gender, aged 18-40 years having class 1 carries in
posterior teeth were included. Teeth with restorations, dentinal sensitivity and
patients taking analgesic drugs for chronic pain conditions were excluded. The
selected patients were placed randomly into Group A (copal varnish) & Group B
(dentin adhesive liner), by using computer generated table of random numbers.
Restored teeth were evaluated 1-month post operatively for sensitivity. RESULTS:
Mean age was 25.63+/-5.42 years. Out of 60 patients, 68.0% were females and 32.0%
were males with a female to male ratio of 2:1. The mean post-operative pain score
was 2.83+/-2.79 in Group A and in Group B, it was 1.43+/-2.14 with a p-value of
0.03. There was no pain on application of a cold stimulus in 14 (46.7%) patients
in Group A (copal varnish) while in Group B (Dentin adhesive), no pain was seen
in 23 (76.7%) patients with p-value of 0.02. CONCLUSIONS: This study concluded
that dentin adhesive liner (dentin bonding agent) is better than copal varnish in
reducing postoperative sensitivity in amalgam restorations.
PMID- 29938412
TI - Efficacy Of Intravenous Lignocain Vs Sevoflurane In Prevention Of Coughing And
Desaturation At Extubation In Children.
AB - BACKGROUND: Inadvertent coughing and desaturation are the most commonly faced and
feared respiratory complications in post-anaesthesia period. The study was done
to compare the efficacy of intravenous lignocaine versus sevoflurane in
prevention of coughing and desaturation at extubation in children less than 6
years of age. METHODS: This Randomized Control Trial was carried out from May
2013 to May 2016, at Combined Military Hospital Nowshera after obtaining approval
from the hospital ethics committee (IREC-0003/5/13/Aneas). Children aged three
months to six years undergoing surgical procedures requiring the placement of
definitive airway were randomly assigned into two groups. Patients were
anaesthetized by standardized balanced anaesthesia technique. In Group A (n=355),
three minutes prior to extubation lignocaine 2% was used intravenously. In Group
B (n=355), isoflurane was switched off, breathing circuit changed and sevoflurane
started at minimum alveolar concentration (MAC 3-4%) for 3 minutes prior to
extubation. Assessment for extubation was clinical. Oxygen saturation and
severity of coughing were noted for 5 consecutive minutes, after extubation.
RESULTS: In group-A, 156 patients were less than 2 years of age while in group-B,
135 patients were less than 2 years old. In group-A, 199 and in group-B, 220
children were 2-6 years of age respectively. Post stratification the p-value for
weight was 0.17 (p-value >0.05) and t-statistic was 1.36. Post stratification p
value for gender was 0.12 (p-value>0.05) and chi square statistic was 2.49. Group
A had more eventful extubation with 270 cases of cough (76%) as compared to group
B where it was noted in 199 cases (56%). Similarly, desaturation was observed in
85 cases in group-A (24%) as compared to 28 cases (8%) in group-B. The difference
between the groups was statistically significant. CONCLUSIONS: Sevoflurane based
anaesthetic vapours mixture causes statistical significant prevention from events
like coughing episodes and desaturation in post-extubation in children less than
six years of age undergoing elective surgery.
PMID- 29938413
TI - Lip Adhesion- A Viable Alternative To Pre-Surgical Orthodontics For The
Management Of Wide Cleft Lips In Third World Countries.
AB - BACKGROUND: Cleft lip and palate is a relatively common condition presenting a
considerable technical challenge, especially the wide cleft (>8 mm), for the
surgeons. Pre-surgical orthodontics, which reduces the cleft width and
facilitates definitive repair, is expensive and not universally available,
especially in the third world. Lip adhesion could be a cheaper alternative to pre
surgical orthodontics. METHODS: This six-year prospective observational study,
from 2010 to 2016, was conducted at the paediatric surgical units of PNS Shifa
Hospital, Karachi and Military Hospital Rawalpindi. All children with wide (8 mm
or more gap in the alveolus) complete ULCP (unilateral cleft lip and palate) were
included in the study. Lip adhesion with concomitant vomer flap palatal repair
was followed by definitive lip repair once the desired moulding, i.e., alveolar
gap <5 mm or adequate narrowing as per surgeon's subjective assessment during the
3 and 6 monthly follow up, had been achieved. RESULTS: A total of 53 children
with the mean age 4.5+/-1.5 months were subjected to surgery, 32 (60.4 %) were
males and 21 (39.6%) were females. The mean gap in the cleft alveolus was 11.1+/
1.7 mm, which was reduced to a mean of 3.2+/-1.3 mm, after a follow up of 4.3+/
1.1 months. The outcome of the lip repair, based on parental satisfaction, was
excellent in 41 (77.3%), good in 10 (18.9%) and poor in 2 (3.8%) cases.
CONCLUSIONS: Lip adhesion is a safe and effective substitute for pre-surgical
orthodontics in wide ULCP.
PMID- 29938414
TI - Comparison Of Solubility And Water Sorption Of Two Different Soft Lining
Material.
AB - BACKGROUND: Soft denture lining materials play a very important role in Removable
Prosthodontics because of their ability to provide a cushioning effect for
maintaining the health of traumatized, swollen and deformed mucosa through
absorption and equal redistribution of stresses over the entire area covered by
denture, thus eliminating the distortion of oral mucosa. The objective of this
investigation is to quantify and relate the mean solubility and water sorption of
acrylic resin based permanent soft liner with a silicone based permanent soft
liner. METHODS: Two different permanent soft denture liners, i.e., acrylic and
silicone based are selected for this study, 30 samples of each material are
prepared in the form of circular disks of the 30 disks, and three subgroups of
ten disks each are made for the two materials. Initially the processed disks will
be weighed 3 times daily with an analytical balance until a constant weight is
achieved. This initial weight of each specimen is denoted by W1. Each subgroup of
10 specimens is immersed in 250 ml of 37 degrees C distilled water in a sealed
polyethylene container. First subgroup is tested after 1 week, second after 4
weeks and third after 6 weeks of immersion. RESULTS: Ever soft has higher
solubility (1.67mg/cm2 +/-0.26 mg/cm2laboratory-processed) and sorption (0.84
mg/cm2 +/-0.35 mg/cm2laboratory-processed) than Molloplast B (0.40 mg/cm2 +/-0.08
mg/cm2solubility and 0.27 mg/cm2 +/-0.16 mg/cm2 sorption) after 6 weeks of
immersion. CONCLUSIONS: It is therefore concluded that Molloplast B may provide
better clinical success based on its lower solubility and water sorption.
PMID- 29938415
TI - Inter-Rater Reliability Of Objective Structured Long Examination Record.
AB - BACKGROUND: Objective Structured Long Examination Record (OSLER) scale was
introduced in 1997 by Gleeson to improve the long case examination. There is no
psychometric evidence to support reliability of OSLER. This study was done to
analyse inter-rater reliability of OSLER. METHODS: Two groups of examiners
assessed 105 students in long case examination of their final professional
examination, using OSLER scale. Group 1 was composed of actual examiners while
Group 2 was mock examiners. Kappa statistic and intraclass correlation
coefficient (ICC) were used on SPSS 23 to calculate reliability. RESULTS: Mean
score awarded by actual examiners was 55.36 (SD=11.2) whereas mean score by mock
examiners was 57.74 (SD=14.1). Cronbach's alpha was 0.586, Kappa was 0.019
whereas inter-rater reliability on ICC was 0.413. CONCLUSIONS: Although OSLER is
a practical modification of long case examination with good validity, the scale
needs to be more structured to improve its reliability.
PMID- 29938416
TI - Mechanism Of Nephroprotection By Picrorhiza Kurroa.
AB - BACKGROUND: Humans are exposed either deliberately or unintentionally to a
variety of diverse chemicals that harm the kidney. To reduce the alarming high
incidence of nephrotoxicity, some chemical as well as herbal alternatives are
needed. Nimesulide belongs to a group of antiinflammatory drugs that are in
common use in our society. Like all non-steroidal antiinflammatory drugs, it
carries a potential threat of nephrotoxicity especially when other risk factors
are present in user. The objective of this study was to find herbal alternative
with antiinflammatory and nephroprotective qualities and to bring into light its
mechanism of nephroprotection. METHODS: This experimental study was conducted on
mice at National Institute of Health, Islamabad from Feb 2013 to March 2014.
Nimesulide was given in a dosage of 750 mg/kg body weight for 3 days to induce
nephrotoxicity and protective effect of Picrorhiza kurroa was noted in two doses
of 250 mg/kg and 500 mg/kg for 14 days. Renal function tests were done and
urinary PGE2 was measured to assess the effect of nimesulide and Pk on kidneys.
RESULTS: In our study, significant improvement was seen in serum urea and
creatinine levels in mice receiving low and high dose Picrorhiza kurroa. However,
no significant improvement was noted in urinary PGE2 showing that the mechanism
of nephroprotection is not by vasodilatory effect of Pk. CONCLUSIONS: This study
showed nimesulide nephrotoxic potential and Pk is a good herbal antiinflammatory
and nephroprotective alternative for nimesulide but its mechanism of
nephroprotection is not by PGE2.
PMID- 29938417
TI - Assessing Family Planning Service Quality And User Experiences In Social
Franchising Programme - Case Studies From Two Rural Districts In Pakistan.
AB - BACKGROUND: Studies have documented the impact of quality family planning
services on improved contraceptive uptake and continuation, however, relatively
little is known about their quality of service provision especially in the
context of social franchising. This study examined the quality of clinical
services and user experiences among two models in franchised service providers in
rural Pakistan. METHODS: This facility-based assessment was carried out during
May-June 2015 at the 20 randomly selected social franchise providers from Chakwal
and Faisalabad. In our case, a franchise health facility was a private clinic
(mostly) run by a single provider, supported by an assistant. Within the selected
health facilities, a total 39 user-provider interactions were observed and same
users were interviewed separately. RESULTS: Most of the health facilities were in
the private sector. Comparatively, service providers at Greenstar Social
Marketing/Population Services International (GSM/PSI) model franchised facilities
had higher number of rooms and staff employed, with more providers' ownership.
Quality of service indices showed high scores for both Marie Stopes Society (MSS)
and GSM/PSI franchised providers. MSS franchised providers demonstrated
comparative edge in terms of clinical governance, better method mix and they were
more user-focused, while PSI providers offered broader range of non-FP services.
Quality of counselling services were similar among both models. Service providers
performed well on all indicators of interpersonal care however overall low scores
were noted in technical care. For both models, service providers attained an
average score of 6.7 (out of the maximum value of 8) on waste disposal mechanism,
supplies 12.5 (out of the maximum value of 15), user-centred facility 2.7 (out of
the maximum value of 4), and clinical governance 6.5 (out of the maximum value of
11) and respecting clients' privacy. The exit interviews yielded high user
satisfaction in both service models. CONCLUSIONS: The findings seem suggesting
that the MSS and GSM/PSI service providers were maintaining high quality
standards in provision of family planning information, services, and commodities
but overall there was not much difference between the two models in terms of
quality and satisfaction. The results demonstrate that service quality and client
satisfaction are an important determinant of use of clinical contraceptive
methods in Pakistan.
PMID- 29938418
TI - Fluoride Release From Glass Ionomer Cement Containing Fluoroapatite And
Hydroxyapatite.
AB - BACKGROUND: Many investigators reported the amount of fluoride release from glass
ionomer cement. However, the work on fluoride release from GIC containing
fluoroapatite and hydroxyapatite is scarce. Therefore, this study was conducted
to find out the amount of fluoride release from Glass ionomer cement containing
fluoroapatite and hydroxyapatite. METHODS: The study was conducted in the
Department of Materials, Queen Marry University of London. A total of 108 samples
equally divided in to three groups namely fluoroapatite added GIC, Hydroxyapatite
added GIC as an experimental group and unmodified GIC as a control group. The
specimens were prepared by mixing powder and liquid in the ratio of 1:1. Amount
of fluoride released was measured by Ion electrode method at 1, 3, 7, 14, 21 and
28 days. RESULTS: On day 1, the combination of FA +GIC showed the highest amount
of fluoride release followed by the control group (GIC) whereas the combination
of HA+GIC released the least amount of fluoride. On day 7, the amount of fluoride
release started declining in all three groups. The amount of fluoride release
continued decreasing on day 21 in which combination of FA +GIC and the control
group are shown to release equal amount of fluoride whereas the combination of
HA+GIC gave the least activity the amount of fluoride release fall to a minimum
level in all three group by day 28. CONCLUSIONS: It is concluded that addition of
fluoroapatite into GIC has significant effect on the amount of fluoride release
as compared to GIC alone; however, addition of hydroxyapatite into GIC has no
additive effect on the amount of fluoride release.
PMID- 29938419
TI - Factors Influencing Medical Students' Choice For Family Medicine As A Specialty
In Pakistan.
AB - BACKGROUND: Multiple factors influence career selection for medical students. In
developed countries, training in family medicine is essential to start practice
as a general practitioner. In Pakistan, this specialty was introduced by College
of Physicians and Surgeons Pakistan in 90's but it has not been yet
institutionalized. This study was conducted to identify the factors that
influence students' choice for Family medicine as a specialty. METHODS: It was a
sequential (quantitative first) mix method study which was conducted in two
medical colleges (one public sector and other private) of Faisalabad from April
to June 2014. In first phase students' career choices were determined in a sample
of 252 students. In second phase 12 students were selected randomly for
interviews; six students who selected family medicine as a specialty and six
students who had selected some other specialty. In depth interviews and focused
group discussion were used to explore the factors that influenced them for
selecting the respective specialty. RESULTS: Major factor for not selecting
family medicine was lack of awareness about the scope of specialty. Other factors
included personal interest, feasibility and family influence. CONCLUSIONS: Lack
of awareness and scope of family medicine is the predominant factor in
influencing students for choosing family medicine as a career. Career
counselling, role modelling and exposure to this specialty during clinical years
can play an important role in promotion of this field.
PMID- 29938420
TI - Efficacy Of 17- Alpha-Hydroxy-Progestrone In Prevention Of Preterm Labour In High
Risk Pregnant Women.
AB - BACKGROUND: Preterm delivery (before 37 completed weeks of gestation) is a major
determinant of infant mortality. The objective of study was to determine the
efficacy of 17-alpha hydroxyprogesterone in preventing delivery before 37 weeks
of gestation in high risk women. METHODS: This study, a randomized controlled
trial was conducted in Obstetrics OPD, observing all scientific and ethical
protocols. The women with less than 20 weeks gestation and with a past history of
preterm delivery were included. A total of 132 women fulfilled the study
requirements. Two groups made were as follows: Group A (Treatment group received
intramuscular 17-alpha hydroxy-progesterone) and Group B served as control (The
control group revived intramuscular Neurobion). A total of 66 women were assigned
to each group. The data was recorded on a specially designed proforma for
statistical analysis and comparison following the standard procedure. RESULTS:
The criterion was strictly observed. The results showed a statistically
significant (p<0.01) difference between group A as compared to group B.
CONCLUSIONS: 17-alpha- Hydroxyprogesterone was found to be an effective drug in
preventing delivery before 37 weeks in women at risk.
PMID- 29938421
TI - Relationship Of Lipids, C-Reactive Protein And Sialic Acid In The Healthy
Individuals.
AB - BACKGROUND: Raised levels of cholesterol and triglycerides are major risk factors
for atherosclerosis, which can lead to coronary heart disease. Both the CRP and
Sialic Acid levels are elevated in response to acute as well as chronic
inflammatory conditions. This study was conducted to determine the serum lipid
profile, CRP and Sialic Acid levels and their relationship with each other in
healthy individuals. METHODS: This was a cross-sectional study performed by the
Department of Biochemistry, Institute of Basic Medical Sciences (IBMS), Khyber
Medical University (KMU) Peshawar. Two hundred healthy subjects in the age group
of 18-50 years of either gender was recruited through consecutive sampling. Blood
sampling were taken from all the participants and analysed each for serum lipid
profile, CRP and Sialic Acid levels through standardized methods. RESULTS: A
total of 200 individuals were included, 53.5% being male. Mean age was 33.39+/
9.76 years. Mean height was 167.86+/-10.8 cm. Mean weight was 66.87+/-11.39kg.
Mean Hip-Waist ratio was 0.93+/-0.16 whereas mean BMI was 24.12+/-3.65. The
simultaneous raised levels of serum lipids, CRP and Sialic Acid were observed
more commonly in females as compared to males. CRP and Sialic Acid has got
statistically significant correlation with HDL. Sialic Acid had statistically
significant correlation with triglycerides in the study population with a
significant p-value (<0.05), while having a non-significant correlation with
total cholesterol and LDL. CRP had got significant correlation with total
cholesterol and LDL and non-significant correlation with triglycerides.
CONCLUSIONS: The study showed that serum CRP and Sialic Acid had a significant
negative correlation with serum HDL. A significant positive correlation was found
between serum Sialic Acid and triglycerides. CRP and Sialic Acid though expensive
but are useful predictors of atherosclerotic disease.
PMID- 29938422
TI - Undergraduate Implant Dentistry Training In Saudi Dental Schools.
AB - BACKGROUND: Implant dentistry training at the undergraduate level has been
introduced only recently in Saudi dental schools and there is only limited data
available about it. The objective of the present study was to evaluate the
current status of undergraduate dental implant education in Saudi Dental Schools.
METHODS: A two-part questionnaire-based study was conducted in Saudi university
dental schools targeted towards undergraduate program directors to assess the
quantity and quality of implant dentistry training being integrated into the
curriculum. In addition, interns were asked to assess the degree of exposure and
their satisfaction regarding implant dentistry education. RESULTS: Five program
directors (83.3%) and 195 interns (82.9%) responded to the questionnaires.
Implant dentistry was taught to the undergraduate students in multidisciplinary
departments with teaching hours ranging from 22-30 hours. Only three schools
exposed students to laboratory (workshop) or clinical training. There was
agreement among the program directors in respect of the didactic contents.
Majority of the interns reportedly acquired knowledge regarding implant dentistry
based on theoretical (96.1%), laboratory (33.5%) and/or clinical (30%) training.
While 50% of the interns agreed to acquire knowledge by assisting and observing
dental implant procedures, only 52.8% of the interns expressed satisfaction
regarding implant dentistry training obtained during their undergraduate period.
CONCLUSIONS: The present study revealed variability in undergraduate implant
dentistry training offered at Saudi dental schools. In order to optimize this and
to produce competent dentists, learning guidelines for such courses should be
developed and implemented by competent authorities.
PMID- 29938423
TI - Perceptions About Treatment Of Psychiatric Disorders By Faith Healers/
Psychiatrists Among General Public Of Urban And Rural Areas Of Rawalpindi
District.
AB - BACKGROUND: With the passage of time, there has been a drastic increase in
psychiatric disorders in past few decades across the world. Due to lack of
education and awareness in the rural community, a majority of people still have
strong misconceptions about the causation of psychiatric disorders and hence
serve as a barrier for their medical treatment. METHODS: A comparative cross
sectional study was conducted in the urban and rural areas of Rawalpindi district
from March to August 2015, to find out the perception about treatment of
psychiatric disorders among general public. Structured closed ended questionnaire
was used to collect data from the participants and the results were analysed
using SPSS. Chi square test was used to determine the association between
categorical variables among urban and rural areas. RESULTS: The finding of our
study confirmed that people of urban areas tend to choose and seek treatment by
psychiatrists more (74%) as compared to those living in rural area that tends to
select and believe in methodology and treatment provided by faith healers (55%).
Lack of education, poor socioeconomic status, high treatment cost and most
importantly false beliefs were the major contributory factors for people of rural
areas in their inclination towards faith healers. CONCLUSIONS: The study
concluded that most of the people of rural areas seek and trust the treatment by
faith healers more as compared to psychiatrists. The importance of education and
insight for the disorder cannot be denied for proper decision making about
treatment choices.
PMID- 29938424
TI - Smoking Cessation After Counselling In Patients Presenting With Acute Coronary
Syndrome.
AB - BACKGROUND: The long-term cardiovascular health risks associated with cigarette
smoking are well established. It is a major risk factor for all manifestations of
coronary artery disease, stroke, and peripheral vascular disease. Patients with
acute coronary syndrome, who quit smoking, reduce their risk of cardiovascular
events immediately and significantly when compared to those who continue smoking.
The study was conducted to determine the frequency of smoking cessation after
counselling in patients presenting with acute coronary syndrome (ACS). METHODS:
Patients of age 35-80 years of either gender presenting with Acute coronary
syndrome presented in emergency within 12 hours of symptoms having history of
smoking (>1pack year for >5 years) were included in the study. A total 225
patients were enrolled in the study from emergency of Punjab institute of
cardiology, Lahore for the duration of six months. Informed consent was obtained
from all patients. Their demographic information was also noted. Then patients
under went counselling session with researcher himself in presence of
psychiatrist from Department of Psychiatry, Services hospital, Lahore. After
admitting patients in ward, patients received standard in-hospital treatment for
smoking cessation which consisted of an assessment of their smoking behaviour and
a personalized brief quit advice. Then patients were followed-up for 12 weeks. On
weekly visit, patients were counselled for smoking cessation. After 12 weeks,
patients were assessed for cessation of smoking. RESULTS: Smoking cessation was
seen in only 37 (16.4%) in ACS patients. Highest frequency of smoking cessation
was seen in patients >65 years of age, i.e., 35.1%. Highest frequency for smoking
cessation was seen in patients whose BMI was <30 (70.3%), patients with low
socioeconomic status (45.9%) and patients with educational status as under matric
(40.5%). None of these factors were significantly associated with smoking
cessation in patients who presented with ACS. CONCLUSIONS: Results of this study
demonstrate low frequency of smoking cessation among patients presenting with
ACS. However, there is a strong need to identify those factors that were
associated with failure to reduce smoking.
PMID- 29938425
TI - Frequency Of Congenital Hearing Loss In Neonates.
AB - BACKGROUND: Congenital deafness is commonest birth defect and it affects 2-4
neonates among 1000 live births. Detection and intervention especially before 6
months of age prevents severe linguistic, educational and psychosocial
repercussions and helps the deaf child in the development of normal speech and
language. Children who are identified after 6 months of age experience great
difficulties in attaining speech and language.. METHODS: To find out the
frequency of hearing loss in neonates, a hospital based observational study was
conducted in Combined Military Hospital Abbottabad from June-to December 2014.
One thousand new-borns selected by consecutive sampling within a specified period
of time were subjected to Otoacoustic Emission (OAE) testing. Brain Evoked
Response Audiometry (BERA) evaluation was performed in all those who failed OAE
testing to confirm the hearing loss. Children born with microtia, meatal
stenosis, cleft palate, craniofacial abnormalities and syndromic illnesses were
excluded from the study. RESULTS: Of 1000 new-borns screened, 465 were males and
535 were females whereas 632 (63.2%) were delivered through C-section and 368
(36.8%) were born via SVD. Four hundred and ninety-one (49%) babies had a
positive history of consanguinity among the parents. Out of 1000 infants 13 were
having hearing loss which was later on confirmed on BERA evaluation. Among them 7
were males and 6 females, 9 (69%) were born through SVD and 4 (31%) through C
section and 8 (61.5%) new-borns had a positive history of consanguinity among
their parents. In all these 13 patients only 2 (15%) patients had profound while
the remaining 11 (85%) had moderate to severe hearing loss. CONCLUSIONS:
Frequency of hearing loss in neonates is much higher in our study (13 per 1000)
as compared to other parts of the world and demands that more studies should be
undertaken on this subject to confirm this.
PMID- 29938426
TI - Domestic Violence Among Pregnant Women.
AB - BACKGROUND: Domestic violence during pregnancy is an important social & health
issue in all societies. In Muslim world and particularly underdeveloped
countries, domestic violence is often under reported. It is the need of hour to
encourage reporting of such events & implementation of research-based policies
for prevention of women abuse & support of the victims of domestic violence (DV).
The objective of this study was to highlight this neglected social problem of our
society & to identify at risk population. METHODS: This is a cross sectional
study conducted at Ayub Teaching Hospital & Benazir Bhutto Shaheed Teaching
Hospital, Abbottabad (January 2014 to December. 2016). Pregnant women were
inquired regarding history of abuse by husband and sociodemographic
characteristics were noted in a Performa to analyse the risk factors for domestic
violence. RESULTS: The overall prevalence was found to be 35%. Out of 1000
pregnant women, 270 (27%) suffered from simple violence and 60 (6%) were victims
of grievous assault. Violence among pregnant women is found to be more prevalent
among residents of urban areas, women of older age being uneducated & belonging
to poor socioeconomic status. CONCLUSIONS: Domestic violence during pregnancy is
a common & often neglected psychosocial health problem. High risk population
needs to be identified so that preventive strategies can be planned &
implemented.
PMID- 29938427
TI - Initial Experience Of Percutaneous Nephrolithotomy In Hazara Region.
AB - BACKGROUND: Renal stone disease affects a large population of the world and
surgical management is the main stay treatment for larger stones. In comparison
to open procedures, percutaneous nephrolithotomy (PCNL) has been known to offer
almost similar stone clearance with least patient morbidity. The study was done
with the objectives to evaluate our initial experience of PCNL in the management
of nephrolithiasis in Abbottabad. METHODS: A case series study was carried out at
a private hospital, Valley Medical Complex, Abbottabad, including the 35 patients
undergoing PCNL from January 2015 to February 2016. RESULTS: Thirty-five patients
(23 male (65.7%) and 12 female (34.3%) underwent PCNL with a mean age of 35.57
years+/-6.701 and mean renal stones size of 24.49 mm+/-7.098. 28.6% stones (n=10)
were located in the renal pelvis, 28.6% (n=10) in the lower pole of kidney and
42.9% (n=15) had stones in other sites of kidney. 25.7% patients (n=9) had mild,
57.1% (n=20) moderate and 17.1% (n=6) had gross hydronephrosis. 28.6% patients
(n=10) had a single renal stone, 61.4% (n=18) had >=2 stones whereas 7 patients
(20%) had partial stag horn stone. Tract access was gained through upper pole in
8.6% patients (n=3), middle pole in 11.4% (n=2), and lower pole in 85.7% (n=30).
Complete stone clearance was achieved in 30 patients (85.7%) whereas partial
clearance accomplished in 3 patients (8.6%). Two patients had PCNL failure due to
failed tract access. Postoperatively 10 patients (28.6%) had significant pain, 06
patients (17.1%) had fever and 1 patients (2.9%) required blood transfusion.
CONCLUSIONS: PCNL is a safe procedure for management of upper urinary tract
stones and is still in evolution stages in Hazara region.
PMID- 29938428
TI - Success And Safety Of Misoprostol For Treatment Of Early Pregnancy Failure.
AB - BACKGROUND: Early pregnancy failure is a common complication in pregnancies. It
can be managed medically as well as surgically. Lately there has been an emphasis
on medical management of early pregnancy failure. Misoprostol, a Prostaglandin E1
analogue has been found to be safe and effective in treatment of early pregnancy
failure. METHODS: This was a descriptive cross-sectional study that was conducted
at the department of gynaecology and obstetrics, Ayub teaching hospital
Abbottabad from Jan 2015 to Dec 2016. A total of 81 pregnant women with early
pregnancy failure were enrolled in the study. Misoprostol was administered in a
dose of 800 MUg PO and repeated every 3 hours for a maximum of three doses if and
when required. RESULTS: Misoprostol was effective in 60 (74.07%) patients and it
resulted in complete expulsion of products of conception. The remainder needed
surgical evacuation. There was a low incidence of side effects with nausea being
the most common (4.94%) followed by PV bleeding (3.70%), abdominal cramps (3.70%)
and diarrhoea (2.47%). CONCLUSIONS: Misoprostol is a safe and effective treatment
option for the management of early pregnancy failure.
PMID- 29938429
TI - Perception Of Health Professionals Towards The Scope Of Family Medicine In The
Healthcare System Of Pakistan.
AB - BACKGROUND: Background: Primary health care is the backbone of comprehensive
healthcare systems, and family physicians complement horizontal health coverage.
In the developed world family medicine is integral to new doctors' training but,
in the developing world, there are hurdles, e.g., poorly targeted financing, lack
of skills and resources, and little health professionals' interest in the
specialty. METHODS: This study determined perceptions of undergraduate and
postgraduate medical trainees and healthcare professionals in Pakistan about
family medicine. Participants' perceptions were examined via a selfadministered
pre-structured questionnaire about family medicine in developing countries before
and after a targeted seminar. Epi Info software (v.7) was used for statistical
analysis. The p-value <0.05 was considered statistically significant. RESULTS:
One hundred & eight questionnaires were returned postseminar demonstrating raised
participant awareness of family medicine, with the majority (postgraduate 90.00%
and undergraduate 90.91%) believing that health departments should create family
medicine specialist posts to encourage students and post-graduate trainees.
Similarly, 89.77% undergraduates and 95.00% postgraduates believed that
comprehensive family medicine in primary health could be a solution to improve
health care in Pakistan. Of note, when asked pre-seminar "do you feel you would
consider family medicine as career speciality?", 42% undergraduates replied yes;
when asked the same question post-seminar 63% of undergraduates and 90% of
postgraduates replied yes. CONCLUSIONS: Introducing family medicine as a subject
in medical colleges will create awareness and interest towards this speciality;
until then, awareness lectures and seminars by trained family physicians will
help bridge the gap towards encouraging students about its benefits.
PMID- 29938430
TI - Axial Spondyloarthritis In Patients With Chronic Backache Using Assessment Of
Spondyloarthritis International Society Criteria For Axial Spondyloarthritis.
AB - BACKGROUND: Low back pain (LBP) is considered as one of the most frequent health
problems which is responsible for forming a huge worldwide burden. This study was
conducted with the aim to determine the frequency of axial-Spondyloarthropathy
(axSpA) in patients presenting with chronic backache using Assessment of
Spondyloarthritis International Society (ASAS) Criteria for axSpA. METHODS: A
total of 231 participants of either gender were enrolled with complaint of
backache of more than or equal to 3 months duration and younger than 45 years. In
the first stage, patients were interviewed and examined using standard
questionnaire. In the second stage after going through laboratory investigations
and imaging patients were classified into either axSpA (those meeting ASAS
Criteria for axSpA) or non-SpA. RESULTS: There were 65 males and 166 females.
Mean age was 36.26 years. Eighty-nine (39%) patients were found to have axSpA as
per ASAS Criteria. Majority of patients 70 (78.6%) in the imaging arm of ASAS
Criteria were picked via MRI of sacroiliac joints. Peripheral arthritis was seen
in 57 (64%) and Enthesitis in 52 (58.4%). CONCLUSIONS: MRI performed
exceptionally to reveal sacroiliitis highlighting the importance of this imaging
modality in axSpA, which we recommend to be included in diagnostic algorithm in
evaluating patients with chronic backache under 45 years age.
PMID- 29938431
TI - Nutritional Assessment Focusing On Women And Children In Palas Valley-Kohistan.
AB - BACKGROUND: Proper nutrition and health are fundamental rights and nutrition is a
cornerstone that affects and defines the health of all people, rich and poor. The
study was done with the objectives to assess the people of Palas valley with
regard to their nutritional status and dietary habits to devise ways and means to
overcome primary and associated reasons for these problems. METHODS: In this
descriptive cross-sectional study residents of Palas valley of district Kohistan
were included in the study through multistage cluster sampling method. The Palas
valley was divided in to two: Kuz Palas (Lower Palas) and Bar Palas (Upper
Palas). Two union council each from Kuz and Bar Palas were randomly selected
Among the households, one adult male, one woman of childbearing age, one male
child and one female child was selected randomly.. RESULTS: A total of 160 adult
and children were interviewed and assessed for the nutritional status. Out of
total of 80 children 61 (76.25%) had visible BCG scars. Among children 77.5% were
either thinly built or had poor built. Among male adults 95% were of normal
built. In adult females, 60% were either of thin built or poor built. Twenty-two
percent of male children and 30% of female children were found underweight.
Fourteen (35%) males and females have a BMI between 17.1-18.5 while only 6 (15%)
of the females have BMI more than 18.5. CONCLUSIONS: Poverty and illiteracy in
the absence of effective social and health services is playing havoc with the
population of Palas valley. Poor sanitation and poor personal hygiene expose them
to infections and parasitic diseases. Poor availability of food, lack of
awareness and tough customs and traditions expose lead to malnutrition.
PMID- 29938432
TI - Treatment Of Breast Cancer; Review And Updates.
AB - Cancer of the breast is the leading female cancer accounting for one fourth of
the malignancies. The tumour remains the most researched, read and practiced upon
around the Globe. The treatment has substantially improved breast cancer related
outcomes, both for early as well as late stages with substantial improvements in
disease free and overall survival. Therapeutic decisions not only rest on
clinical & tumour characteristics, but also with the evolution of molecular
biology and tissue microarray intrinsic sub-types have been found. Attempts are
being made to translate therapy from genomic architecture of individual breast
cancer. This facilitates customization of treatment avoiding un-necessary
toxicity, costs and inconvenience. Optimizing treatment based on individual
breast biology seems logical and allows unifying treatment. The paper reviews
literature, incorporate updates and also describes immunohistochemistry based
molecular classification: which are found simple to adapt, record, present and
subsequently manage, summarizing clinical practices in management of these
patients.
PMID- 29938433
TI - Aphallia: A Very Rare Congenital Anomaly, With Associated Genitourinary And Ano
Rectal Malformation.
AB - Aphallia or penile agenesis is very rare congenital anomaly of unknown cause
occurring 1 in 30 million live births. Very little has been written in literature
about aphallia. There is absent phallus and urethra may open abnormally in
perineum or into rectum posing various surgical, social and psychological
implications as the child grows. We are presenting 03 cases of aphallia with
associated congenital anomalies such as unilateral renal agenesis, bilateral
undescended testes, anorectal malformation and rectovasical fistula.
PMID- 29938434
TI - Metastatic Cardiac Melanoma With T-Wave Inversions.
AB - A woman in her 70's with a background of ocular malignant melanoma treated more
than a decade ago was admitted to hospital with symptoms of dysphagia and
exertional shortness of breath. Routine ECG showed a grossly abnormal ECG with T
wave inversion in inferolateral leads and some anterior leads. Consequently,
echocardiography and CT demonstrated the presence of a large pericardial tumour
which on biopsy was found to be metastatic melanoma. Patient was treated with
palliative radiotherapy with only temporary initial benefit.
PMID- 29938435
TI - Spontaneous Right Coronary Artery Dissection In A Normotensive Post-Partum
Female.
AB - Acute myocardial infarction following coronary artery dissection during the post
partum period is a rare entity. Greater hemodynamic stress and hormonal changes
increase the risk of developing a coronary artery dissection post-partum. Herein,
we report the first case of a normotensive patient from Pakistan that presented
with inferior wall myocardial infarction following 10-days postpartum due to
right coronary artery dissection. This article highlights the importance of
prompt diagnosis and subsequent life-saving treatment.
PMID- 29938436
TI - Thyroid Abscess In Children: And The World Gets Stranger.
AB - The eminent feature of the thyroid gland in its resistance to infection by virtue
of a rich blood supply and lymphatic drainage. Concomitantly, high iodine content
is also bactericidal. Acute suppurative thyroiditis, which leads to primary
thyroid abscess, is an unusual type of head and neck infection. And above all, if
it is in a paediatric age; it is quite rare. We have the opportunity to present
such a noticeable case which was treated successfully by oral antibiotic therapy.
PMID- 29938437
TI - Rare Case Of Primary Congenital Glaucoma With Hypoplasia Corpus Callosum.
AB - : Primary congenital glaucoma is a rare disease that causes elevated intraocular
pressure within the first three years of life. Few studies have explored the
association of primary congenital glaucoma with malformation of corpus callosum.
We report on a six-month-old female presenting with unilateral primary congenital
glaucoma associated with hypoplasia of corpus callosum in Indonesian infant. The
patient had already undergone trabeculectomy surgery. However, there no obvious
improvement following the procedure given the severity of the condition.
CONCLUSION: The failure rate of surgery in severe primary congenital glaucoma
conditions is still very high, and therapy can usually preserve vision if early
identification of mild or moderate form is made.
PMID- 29938438
TI - Macrophage Activation Syndrome Associated With Adult Onset Still's Disease.
AB - Macrophage activation syndrome (MAS) is a potentially lethal complication of
chronic rheumatological conditions like ankylosing spondylitis, rheumatoid
arthritis, and adult-onset Still's disease (AOSD). It is a multisystem
inflammatory syndrome caused by immense cytokine release from activated
lymphocytes and macrophages. We give an account of the incidence of a twenty
years old Asian girl suffering from non-remitting fever and an evanescent rash
for last ten weeks. Physical examination and laboratory work-up suggested high
grade fever, pancytopenia, hyperferritinemia, hypertriglyceridemia,
hypofibrinogenemia and impaired liver function. Bone marrow biopsy was also done.
It showed active hemophagocytosis. She was diagnosed as a case of Macrophage
Activation Syndrome associated with Adult Onset Still's disease. She was treated
with high dose steroids and cyclosporine and recovered completely.
PMID- 29938439
TI - Forgotten Post Operative Nasal Splint & Oro-Nasal Fistula.
AB - of the oral cavity. It may develop as a congenital defect e.g. cleft palate, or
rarely, consequent to an operative procedure like a sub muco-perichondrial
resection surgery of the nasal septum. After nasal septal corrective surgery,
follow up of the patient with meticulous nasal toilet and detailed examination is
mandatory. In operated patients who do not report to follow up, and later on
present with persisting nasal discharge, pain, nasal blockage and exsanguination
must alert a clinician for any evidence of a possibly retained foreign object.
Inadvertently retained nasal splints can cause long lasting morbidity due to a
possible chronic sinusitis, toxic shock syndrome and palatal perforation.
PMID- 29938440
TI - Gastric Emptying Scintigraphy In Assessment Of Chronic Vomiting.
AB - Gastroparesis being multifocal abnormality is characterized by objective feeling
of prolong time of gastric retention without any evidence of anatomical blockage.
The key symptoms include early satiety, feeling of fullness after meals, nausea,
vomiting, bloating, and upper abdominal pain. Radio isotopic Gastric emptying
study using radiolabelled test food is integrated clinically for evaluation of
functional gastric motility disorders. We present a young female having abdominal
pain and vomiting for two months. She was investigated for anatomical causes and
no abnormality was uncovered. Gastric Emptying scintigraphy revealed delayed lag
phase and half gastric emptying time consistent with the diagnosis of
Gastroparesis.
PMID- 29938441
TI - Resolution Of Gestational Gigantomastia With Termination Of Pregnancy.
AB - Less than 100 cases of gestational gigantomastia have been described in
literature. The aetiology and risk factors are not well-established. Various
treatments have been used with some consensus. We present the case of a 47-year
old female who presented to us with bilateral gigantomastia in her 16th week of
gestation. She had massively enlarged breasts which were very painful. Relevant
laboratory investigations were normal. An incisional biopsy done prior to, and
two trucut samples at presentation to us, showed normal breast tissue
proliferation. In the absence of adequate pain control, it was decided to
electively terminate the pregnancy and give a trial of tamoxifen. She made a
rapid recovery following termination without requiring the use of tamoxifen.
PMID- 29938442
TI - Low hba1c; Is It Dapsone?
AB - A 51-year-old male was referred to the diabetes clinic by the GP with low HbA1c
(13 mmol/mol). His complaints were dizziness and intermittent palpitations for
the last two years. No precipitating cause could be identified. He denied any
chest pain, shortness of breath or syncope. He had a background of schizophrenia,
epilepsy, coeliac disease, depression and dermatitis herpetiformis. He was on
dapsone, venlafaxine, procyclidine, furosemide, diazepam, omeprazole, meloxicam
and folic acid. On examination, his pulse was 82 beats per minute, blood pressure
131/74 mm of Hg, respiratory rate was 14/minute and his saturations on room air
were 94%. Neurologic, cardiovascular, respiratory and abdominal examination was
unremarkable. His investigations showed Hb of 121g/L (130-180) WCC 7.8*10 g/L (4
11), platelets 182*10 (150-400), MCV 83 fl (80-100), TSH 2.53 mU/L (0.4-4.0
mU/L), anti TTG 14.9 (normal). Renal, liver function, serum folate, vitamin B12
and complement levels were within normal limits with a negative ANCA and ANA. His
oral glucose tolerance test was negative for diabetes with fasting and twohour
post prandial blood sugar of 4.8mmol/L and 6.9 mmol/L respectively. Because of
the history of chronic Dapsone use and possibility of drug induced low HbA1C,
patient was investigated along those lines. The low Hba1c was attributed to
haemolysis secondary to dapsone. HbA1c improved to 42 mmol/mol within three
months following discontinuation of dapsone. His haemoglobin level also
normalized (142 g/L). Clinicians should consider haemolysis as a possible factor
falsely reducing HbA1c while interpreting results in these patients. This is of
particular importance in patients with diabetes.
PMID- 29938443
TI - Polio Elimination In Pakistan: Still A Dream?
AB - Pakistan has failed to achieve polio elimination till yet. Poliomyelitis is a
crippling childhood disease, which causes paralysis for life. Aim of this study
is to compare the frequency of polio cases in different provinces of Pakistan
from 2010 till 2017. Results showed that total of 144 cases of polio were
reported in 2010, a rise up to 198 was reported in 2011, a decline in cases was
seen in 2012, i.e., 58, again cases rouse up to 93 cases, in 2013. In 2014, 306
cases were reported the rate declined considerably in 2015, i.e., 54 cases and in
2016 only 20 cases were seen. In 2017 only 8 cases were reported. So, it can be
concluded that progressive improvement is seen in Pakistan regarding polio.
Focused efforts should be continued till its complete elimination from the
country as this will also give a positive message to the world about Pakistan
being a responsible and peaceful nation.
PMID- 29938444
TI - Sample Size Determination In Health Research.
AB - One of frequently asked question by medical and dental students / researchers is
how to determine the sample size. Sample size calculations is necessary for
approval of research projects, clearance from ethical committees, approval of
grant from funding bodies, publication requirement for journals and most
important of all justify the authenticity of study results. Determining the
sample size for a study is a crucial component. The goal is to include sufficient
numbers of subjects so that statistically significant results can be detected.
Using too few subjects' will result in wasted time, effort, money; animal lives
etc. and may yield statistically inconclusive results. There are numerous
situations in which sample size is determined that varies from study to study.
This article will focus on the sample size determination for hypothesis testing
that involves means, one sample t test, two independent sample t test, paired
sample and one-way analysis of variance.
PMID- 29938445
TI - Gut-Brain Axis Hypothesis-An Innovative Way To Cure Parkinson In Pakistan?
PMID- 29938446
TI - A Molar Tooth Brainstem With A Bat-Wing Fourth Ventricle: Joubert Syndrome.
PMID- 29938447
TI - Dermoscopy Of Oral Squamous Cell Carcinoma.
PMID- 29938448
TI - [Progress of fMRI Research on "Deqi" of Acupuncture and Our Considerations About
Further Studies].
AB - The objectification of "Deqi" of acupuncture is a hot topic in acupuncture
research at present, and functional magnetic resonance imaging (fMRI) is one of
the most frequently-used techniques for revealing its brain responses. We
searched literature about "Deqi" from PubMed in recent 10 years by using key
words "Deqi""acupuncture sensation""needling sensation" and fMRI, trying to
expound the central mechanism of "Deqi" and to put forward our understandings.
Acupuncture "Deqi" evoked deactivation of the limbic-paralimbic-neocortical
network (LPNN)/ default mode network (DMN), including medial prefrontal cortex
(frontal pole, anterior cingulate), temporal lobe (amygdala, hippocampus,
parahippocampus gyrus, temporal pole), and apparent activation of brain regions
as the somatosensory cortex, thalamic-somatosensory area-insular lobe,
orbitofrontal cortex, etc., which may enhance the connectivity of brain networks
and function in analgesia, anti-anxiety, anti-depression, etc., but the activated
and deactivated brain regions are different from study to study possibly due to
the stimulated different acupoints, subjects' psychophysical conditions, scanning
parameters, image acquiring sequences, etc. It is recommended that the coming stu
dies should pay more attention to the influence of acupuncture "Deqi" on brain
functions in subjects suffering from diseases, the brain response characteristics
of the longer post-effects and the accumulated effects of acupuncture treatment.
PMID- 29938449
TI - Assessing and managing communication needs in people with serious mental illness.
AB - Effective communication is essential to maintain mental health and resilience.
Communication can be challenging for people who experience serious mental illness
(SMI), which can be a barrier to social, employment and educational
opportunities, as well as increasing their risk of experiencing abuse. Therefore,
it is important that nurses who work with individuals experiencing SMI understand
the assessment and management of specific communication, speech and language
needs. This article focuses on five areas of communication, speech and language -
receptive language, expressive language, speech, social communication and
swallowing - to increase nurses' confidence in assessing communication needs and
making appropriate referrals to speech and language therapy services. The authors
also suggest therapeutic interventions that nurses can use to reduce the effects
of speech and language difficulties among people with SMI.
PMID- 29938450
TI - Non Size Based Morphology Criteria for Assessment of Response in Patients with
Liver Metastases of Gastrointestinal Origin Receiving Systemic Treatment
AB - Background and Aim: Liver is the main site of metastases of gastrointestinal
cancers, chemotherapy with orwithout targeted therapy is the standard treatment.
Radiologic assessment of tumor response is usually done bythe use of Response
Evaluation Criteria in Solid Tumor (RECIST) criteria. RECIST depends on tumor
size changes butit does not address morphologic changes as overall attenuation,
enhancement and tumor liver interface changes whichmay shown early before tumor
size changes. We aimed to evaluate use of contrast enhanced computed
tomography(CECT) new morphologic criteria in assessment of response in patients
with hepatic metastases of gastrointestinalorigin. Methods: This study was
carried out by cooperation between Clinical Oncology and Nuclear Medicine
andRadiodiagnosis Departments, Faculty of Medicine, Menoufia University. During
the period from April 2015 to December2016 forty patients with stage IV
gastrointestinal cancers with hepatic metastases were included, CECT was
donebefore and after systemic treatment, response evaluation was done by RECIST
1.1 and morphology response criteriac.Results: By RECIST, partial response (PR)
observed in 57.5%, stable disease (SD) 22.5% and progressive disease (PD)in 20%
of patients compared to Optimal response 42.5%, incomplete response 35% and no
response in 22.5% of patientsby Morphologic response criteria. Regarding
survival, patients with PR had median survival of 20 months (95% CI,17.988 to
22.012months) versus 11 months (95% CI, 1.235 to 8.580 months) in SD or PD by
RECIST, (P=.002). whileby morphology response criteria the median overall
survival of optimally responded patients 23 months (95% CI, 20.04to 27.81months)
versus 16 months (95% CI, 5.590 to 5.044 months) in patients with incomplete or
no morphologicresponse (P=.001). Conclusion: Morphologic response criteria are
accurate method for assessment of response ofhepatic metastases and correlated
well with patients' survival and better to be incorporated to treatment
evaluation.
PMID- 29938451
TI - Assessment of Depression and Anxiety in Breast Cancer Patients: Prevalence and
Associated Factors
AB - Introduction: Having breast cancer or receiving treatment has been seen as a
traumatic experience for women dueto its impacts on their self-image and sexual
relationship, and may lead to an psychological reactions such as denial,anger, or
intense fear toward their disease and treatment process. Also many of breast
cancer patients have psychiatricmorbidities such as depression and anxiety.
Purpose: The purpose of this study was to assess the prevalence andassociated
factors of depression and anxiety in breast cancer patients, in order to identify
independent predictors of mentalhealth disorders risk. Material and Methods: A
cohort of 152 breast cancer patients who were attending an outpatientoncology
department was recruited. Data were collected with a structured questionnaire
consisted by social, clinicaland demographic information and PHQ-2 and GAD-2
scales. Results: The mean age of the patients was 53.25 years(SD=12.10), 69.7% of
the patients underwent mastectomy and 30.3% ongectomy. Chemotherapy received
46.1% ofpatients as adjuvant therapy, 15.8% radiotherapy and 38.2% received both
chemotherapy and radiotherapy. A largepercentage found to be classified as
depressed (38.2%) and anxious (32.2%) and factors that found to be associatedwere
age, marital status, educational level, stage of cancer from univariate analyses
and place of residence, religion,symptoms burden from multivariate analysis (for
depression and anxiety). Conclusions: Breast cancer patients arein high risk for
developing psychiatric disorders such as depression and anxiety. Being rural
resident, non-OrthodoxChristian and experiencing extend symptom burden can be
predicting factors associated with depression and anxietyin breast cancer
patients.
PMID- 29938452
TI - Efficacy and Safety of UI05MSP015CT in Functional Dyspepsia: A Randomized,
Controlled Trial.
AB - Background/Aims: To evaluate the efficacy and safety of a controlled release,
once-daily formulation of mosapride (UI05MSP015CT) in patients with functional
dyspepsia (FD). Methods: Patients with FD were randomly assigned (1:1) to receive
either UI05MSP015CT (15 mg once a day, study group) or mosapride (5 mg three
times a day, control group) and corresponding placebo for 4 weeks. The primary
endpoint was a change in the gastrointestinal symptom score (GIS) evaluated at
enrollment and after 4 weeks. Secondary endpoints were changes in the Nepean
Dyspepsia Index-Korean version (NDI-K), rate of satisfactory symptom relief, and
rate of adverse events. Results: A total of 138 patients were enrolled (female,
73.9%; mean age, 44.0+/-15.4 years). After excluding patients who violated the
study protocol, 59 and 58 patients from the study and control groups,
respectively, were included in the per-protocol analysis. No difference was
observed in drug compliance between the control and study groups (97.07%+/-4.52%
vs 96.85%+/-6.05%, p=0.870). Changes in GIS scores were -9.69+/-6.44 and -10.01+/
5.92 in the study and control groups. The mean difference in GIS change between
groups was 0.33 (95% confidence interval, -1.75 to 2.41), demonstrating non
inferiority of UI-05MSP015CT (p=0.755). The rate of satisfactory symptom relief
was not different between the study and control groups (39.0% vs 56.9%, p=0.053).
No differences in change in NDI-K score (14.3 vs 16.9, p=0.263) or rates of
adverse events (12.9% vs. 4.4%, p=0.062) were observed between the study and
control groups. Conclusions: Once-daily mosapride is not inferior to conventional
mosapride in efficacy and is safe in patients with FD.
PMID- 29938453
TI - Prospective Multicenter Study of the Challenges Inherent in Using Large Cell-Type
Stents for Bilateral Stent-in-Stent Placement in Patients with Inoperable
Malignant Hilar Biliary Obstruction.
AB - Background/Aims: Although endoscopic bilateral stent-in-stent placement is
challenging, many recent studies have reported promising outcomes regarding
technical success and endoscopic re-intervention. This study aimed to evaluate
the technical accessibility of stent-in-stent placement using large cell-type
stents in patients with inoperable malignant hilar biliary obstruction. Methods:
Forty-three patients with inoperable malignant hilar biliary obstruction from
four academic centers were prospectively enrolled from March 2013 to June 2015.
Results: Bilateral stent-in-stent placement using two large cell-type stents was
successfully performed in 88.4% of the patients (38/43). In four of the five
cases with technical failure, the delivery sheath of the second stent became
caught in the hook-cross-type vertex of the large cell of the first stent, and
subsequent attempts to pass a guidewire and stent assembly through the mesh
failed. Functional success was achieved in all cases of technical success. Stent
occlusion occurred in 63.2% of the patients (24/38), with a median patient
survival of 300 days. The median stent patency was 198 days. The stent patency
rate was 82.9%, 63.1%, and 32.1% at 3, 6, and 12 months postoperatively,
respectively. Endoscopic re-intervention was performed in 14 patients, whereas 10
underwent percutaneous drainage. Conclusions: Large cell-type stents for
endoscopic bilateral stent-in-stent placement had acceptable functional success
and stent patency when technically successful. However, the technical difficulty
associated with the entanglement of the second stent delivery sheath in the hook
cross-type vertex of the first stent may preclude large cell-type stents from
being considered as a dedicated standard tool for stent-in-stent placement.
PMID- 29938454
TI - Frequency and Characteristics of Interval Colorectal Cancer in Actual Clinical
Practice: A KASID Multicenter Study.
AB - Background/Aims: The aims of the present study were to determine the frequency of
interval colorectal cancers (CRCs) after surveillance colonoscopy and to compare
the clinicopathologic features and survival outcomes with those of non-interval
CRCs. Methods: From January 2003 to December 2013, 66,016 follow-up colonoscopies
for 38,412 patients performed within recommended time were reviewed
retrospectively based on data from 11 tertiary hospitals in South Korea. To
compare clinicopathologic features and survival rates for interval CRC, 106
patients with non-interval CRC matched in age and gender were included. Results:
Among the 66,016 colonoscopies performed within the surveillance period, 63 cases
(63/66,016) of interval CRC were detected, and 53 were finally included in the
analysis. The mean age was 69.9+/-8.8 years, and the male to female ratio was
1.94:1. Although the occurrence rate of cancer in the right side colon was higher
than that of non-interval CRC, interval CRCs were predominantly left sided. Other
clinicopathologic features and overall survival were not significantly different
between the two groups. Missed lesion was suspected to be the most common cause
(29 cases, 54.7%). Conclusions: The frequency of interval CRC among patients who
had undergone a surveillance colonoscopy was 0.095%. While sharing some similar
clinical features and survival outcomes, interval CRCs in Korea developed more
often in males and on the left side in contrast to results from Western studies.
PMID- 29938455
TI - Optimal Starting Age for Colorectal Cancer Screening in an Era of Increased
Metabolic Unhealthiness: A Nationwide Korean Cross-Sectional Study.
AB - Background/Aims: The association between metabolic syndrome and colorectal cancer
(CRC) has been suggested as one of causes for the increasing incidence of CRC,
particularly in younger age groups. The present study examined whether the
current age threshold (50 years) for CRC screening in Korea requires modification
when considering increased metabolic syndrome. Methods: We analyzed data from the
National Health Insurance Corporation database, which covers ~97% of the
population in Korea. CRC risk was evaluated with stratification based on age and
the presence/absence of relevant metabolic syndrome components (diabetes,
dyslipidemia, and hypertension). Results: A total of 51,612,316 subjects enrolled
during 2014 to 2015 were analyzed. Among them, 19.3% had diabetes, hypertension,
dyslipidemia, or some combination thereof. This population had a higher incidence
of CRC than did those without these conditions, and this was more prominent in
subjects <40 years of age. The optimal cutoff age for detecting CRC, based on the
highest Youden index, was 45 years among individuals without diabetes,
dyslipidemia, and hypertension. Individuals with at least one of these components
of metabolic syndrome had the highest Youden index at 62 years old, but the value
was only 0.2. Resetting the cutoff age from 50 years to 45 years achieved a 6%
increase in sensitivity for CRC detection among the total population.
Conclusions: Starting CRC screening earlier, namely, at 45 rather than at 50
years of age, may improve secondary prevention of CRC in Korea.
PMID- 29938456
TI - Balloon-Occluded Retrograde Transvenous Obliteration versus Transjugular
Intrahepatic Portosystemic Shunt for the Management of Gastric Variceal Bleeding.
AB - Background/Aims: Gastric varices (GVs) are a major cause of upper
gastrointestinal bleeding in patients with liver cirrhosis. The current
treatments of choice are balloon-occluded retrograde transvenous obliteration
(BRTO) and the placement of a transjugular intrahepatic portosystemic shunt
(TIPS). We aimed to compare the efficacy and outcomes of these two methods for
the management of GV bleeding. Methods: This retrospective study included
consecutive patients who received BRTO (n=157) or TIPS (n=19) to control GV
bleeding from January 2005 to December 2014 at a single tertiary hospital in
Korea. The overall survival (OS), immediate bleeding control rate, rebleeding
rate and complication rate were compared between patients in the BRTO and TIPS
groups. Results: Patients in the BRTO group showed higher immediate bleeding
control rates (p=0.059, odds ratio [OR]=4.72) and lower cumulative rebleeding
rates (log-rank p=0.060) than those in the TIPS group, although the difference
failed to reach statistical significance. There were no significant differences
in the rates of complications, including pleural effusion, aggravation of
esophageal varices, portal hypertensive gastropathy, and portosystemic
encephalopathy, although the rate of the progression of ascites was significantly
higher in the BRTO group (p=0.02, OR=7.93). After adjusting for several
confounding factors using a multivariate Cox analysis, the BRTO group had a
significantly longer OS (adjusted hazard ratio [aHR]=0.44, p=0.01) and a longer
rebleeding-free survival (aHR=0.34, p=0.001) than the TIPS group. Conclusions:
BRTO provides better bleeding control, rebleeding-free survival, and OS than TIPS
for patients with GV bleeding.
PMID- 29938457
TI - Development of a Novel Endoscopic Scoring System to Predict Relapse after Surgery
in Intestinal Behcet's Disease.
AB - Background/Aims: The cumulative surgery rate and postoperative relapse of
intestinal Behcet's disease (BD) have been reported to be high. This study aimed
to establish a scoring system based on follow-up endoscopic findings that can
predict intestinal BD recurrence after surgery. Methods: Fifty-four patients with
intestinal BD who underwent surgery due to bowel complications and underwent
follow-up colonoscopy were retrospectively investigated. Their clinical data,
including colonoscopic findings, were retrieved. Classification and regression
tree analysis was used to develop an appropriate endoscopic classification model
that can explain the postsurgical recurrence of intestinal BD most accurately
based on the following classification: e0, no lesions; e1, solitary ulcer <20 mm
in size; e2, solitary ulcer >=20 mm in size; and e3, multiple ulcers regardless
of size. Results: Clinical relapse occurred in 37 patients (68.5%). Among 38
patients with colonoscopic recurrence, only 29 patients had clinically relapsed.
Multivariate analysis identified higher disease activity index for intestinal BD
at colonoscopy (hazard ratio [HR], 1.013; 95% confidence interval [CI], 1.005 to
1.021; p=0.002) and colonoscopic recurrence (HR, 2.829; 95% CI, 1.223 to 6.545;
p=0.015) as independent risk factors for clinical relapse of intestinal BD.
Endoscopic findings were classified into four groups, and multivariate analysis
showed that the endoscopic score was an independent risk factor of clinical
relapse (p=0.012). The risk of clinical relapse was higher in the e3 group
compared to the e0 group (HR, 6.284; 95% CI, 2.036 to 19.391; p=0.001).
Conclusions: This new endoscopic scoring system could predict clinical relapse in
patients after surgical resection of intestinal BD.
PMID- 29938458
TI - Increased Expression of the Matrix-Modifying Enzyme Lysyl Oxidase-Like 2 in
Aggressive Hepatocellular Carcinoma with Poor Prognosis.
AB - Background/Aims: Lysyl oxidase-like 2 (LOXL2), a collagen-modifying enzyme, has
been implicated in cancer invasiveness and metastasis. Methods: We evaluated the
expression of LOXL2 protein, in addition to carbonic anhydrase IX (CAIX), keratin
19, epithelial cell adhesion molecule, and interleukin 6, in 105 resected
hepatocellular carcinomas (HCCs) by immunohistochemistry. Results: LOXL2
positivity was found in 14.3% (15/105) of HCCs, and it was significantly
associated with high serum alpha-fetoprotein levels, poor differentiation,
fibrous stroma, portal vein invasion, and advanced TNM stage (p<0.05 for all).
Additionally, LOXL2 positivity was significantly associated with CAIX (p=0.005)
and stromal interleukin 6 expression (p=0.001). Survival analysis of 99 HCC
patients revealed LOXL2 positivity to be a poor prognostic factor; its prognostic
impact appeared in progressed HCCs. Furthermore, LOXL2 positivity was shown to be
an independent predictor of overall survival and disease-specific survival
(p<0.05 for all). Interestingly, co-expression of LOXL2 and CAIX was also an
independent predictor for overall survival, disease-specific survival, disease
free survival, and extrahepatic recurrence-free survival (p<0.05 for all).
Conclusions: LOXL2 expression represents a subgroup of HCCs with more aggressive
behavior and is suggested to be a poor prognostic marker in HCC patients.
PMID- 29938459
TI - Real-World Clinical Efficacy and Tolerability of Direct-Acting Antivirals in
Hepatitis C Monoinfection Compared to Hepatitis C/Human Immunodeficiency Virus
Coinfection in a Community Care Setting.
AB - Background/Aims: Limited data exist comparing the safety and efficacy of direct
acting antivirals (DAAs) in hepatitis C virus (HCV) monoinfected and HCV/human
immunodeficiency virus (HIV) coinfected patients in the real-world clinic
practice setting. Methods: All HCV monoinfected and HCV/HIV coinfected patients
treated with DAAs between January 2014 and October 2017 in community clinic
settings were retrospectively analyzed. Pretreatment baseline patient
characteristics, treatment efficacy, factors affecting sustained virologic
response at 12 weeks (SVR12) after treatment, and adverse reactions were compared
between the groups. Results: A total of 327 patients were included in the study,
of which 253 were HCV monoinfected, and 74 were HCV/HIV coinfected. There was a
statistically significant difference observed in SVR12 when comparing HCV
monoinfection and HCV/HIV coinfection (94% and 84%, respectively, p=0.005).
However, there were no significant factors identified as a predictor of a reduced
response. The most common adverse effect was fatigue (27%). No significant drug
interaction was observed between DAA and antiretroviral therapy. None of the
patients discontinued the treatment due to adverse events. Conclusions: In a real
world setting, DAA regimens have lower SVR12 in HCV/HIV coinfection than in HCV
monoinfection. Further studies involving a higher number of HCV/HIV coinfected
patients are needed to identify real predictors of a reduced response.
PMID- 29938460
TI - Clinical Implication and Risk Factors for Malignancy of Atypical Gastric Gland
during Forceps Biopsy.
AB - Background/Aims: Although forceps biopsy is performed for suspicious gastric
tumors during endoscopy, it is difficult to determine treatment strategies for
atypical gastric glands due to uncertainty of the diagnosis. The aim of this
study was to investigate clinical implications and risk factors for predicting
malignancy in atypical gastric glands during forceps biopsy. Methods: We
retrospectively reviewed medical records of 252 patients with a diagnosis of
atypical gastric gland during forceps biopsy. Predictors of malignancy were
analyzed using initial endoscopic findings and clinical data. Results: The final
diagnosis for 252 consecutive patients was gastric cancer in 189 (75%), adenoma
in 26 (10.3%), and gastritis in 37 (14.7%). In the multivariate analysis, lesion
sizes of more than 10 mm (odds ratio [OR], 3.021; 95% confidence interval [CI],
1.480 to 6.165; p=0.002), depressed morphology (OR, 3.181; 95% CI, 1.579 to
6.406, p=0.001), and surface nodularity (OR, 3.432; 95% CI, 1.667 to 7.064,
p=0.001) were significant risk factors for malignancy. Conclusions: Further
evaluation and treatment should be considered for atypical gastric gland during
forceps biopsy if there is a large-sized (>10 mm) lesion, depressed morphology,
or surface nodularity.
PMID- 29938461
TI - Regulatory Dendritic Cells Induced by Mesenchymal Stem Cells Ameliorate Dextran
Sodium Sulfate-Induced Chronic Colitis in Mice.
AB - Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by
mesenchymal stem cells (MSCs), play an important role in inducing and maintaining
homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In
this study, we investigated whether MSCs could differentiate DCs into rDCs and
compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)
induced chronic colitis mice. Methods: Immature DCs (imDCs) and
lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for
48 hours, and then the profiles of surface markers and cytokines and regulatory
roles of these DCs for primary splenocytes were analyzed. In addition, the
therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in
chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated
mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6
(IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN
gamma), was decreased, but that of CD11b, IL-10, and transforming growth factor
beta (TGF-beta) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the
expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In
DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight,
and survival rate and induced histological improvement. Moreover, in the colon
tissues, the expression of IL-6, TNF-alpha, and IFN-gamma decreased, but that of
IL-10, TGF-beta, and Foxp3 increased in the MSC- and MSC-DC-injected groups.
Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which
ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically
useful for the treatment of chronic inflammatory diseases.
PMID- 29938462
TI - Incidence and Overall Survival of Biliary Tract Cancers in South Korea from 2006
to 2015: Using the National Health Information Database.
AB - Background/Aims: There have been no nationwide studies to investigate the trends
in incidence and 5-year survival rates of intra- and extrahepatic bile duct
cancers and gallbladder cancer. Therefore, our study aimed to describe the
incidence and 5-year survival rates of biliary tract cancers by subsites in South
Korea. Methods: A total of 86,134 patients with biliary tract cancers were
selected from the National Health Information Database. Age-standardized
incidence rates and annual percentage changes were calculated. Life-table methods
and log-rank tests were used to determine the differences in survival rates. Cox
proportional hazard models were used to estimate the hazard ratio of the patients
with biliary tract cancers. Results: The incidence rate of intrahepatic bile duct
cancer decreased by 1.3% annually from 8.8 per 100,000 in 2006 to 7.8 per 100,000
in 2015. Extrahepatic bile duct cancer also showed a decreasing trend by 2.2% per
year from 8.7 per 100,000 in 2006 to 6.7 per 100,000 in 2015. Gallbladder cancer
showed the greatest decline, with an annual percentage change of 2.8% from 6.3
per 100,000 to 5.2 per 100,000 during the same period. The 5-year survival rates
were 30.0% in gallbladder cancer, 27.8% in extrahepatic bile duct cancer, and
15.9% in intrahepatic bile duct cancer. Conclusions: The overall incidence rates
of intrahepatic and extrahepatic bile duct cancer and gallbladder cancer
decreased from 2006 to 2015. Among biliary tract cancers, intrahepatic bile duct
cancers exhibited the highest incidence rate and the worst survival rate.
PMID- 29938463
TI - Prevalence and Risk Factors of Functional Dyspepsia in Health Check-up
Population: A Nationwide Multicenter Prospective Study.
AB - Background/Aims: Functional dyspepsia (FD) is one of the most common
gastrointestinal disorders, and FD imposes social and economic burden worldwide.
The aim of this study is to identify the prevalence and risk factors of FD in
health check-up population in tertiary centers in Korea. Methods: A nationwide
multicenter prospective study was performed at 9 tertiary healthcare centers in
Korea between September 2016 and June 2017. A total of 2525 subjects were
investigated based on endoscopic findings and questionnaires with the Rome III
criteria, and Helicobacter pylori serology (IgG). Results: A total of 1714
subjects without organic disease were enrolled. The mean (+/- SD) age was 51.5
(+/- 12.7) years, and 917 patients (53.5%) were female. The proportion of H.
pylori seropositivity was 51.0% (874/1714). The prevalence of FD was 10.3%
(176/1714), and the subtypes of postprandial distress syndrome alone, epigastric
pain syndrome alone, and postprandial distress syndrome-epigastric pain syndrome
overlap were 4.8%, 3.0%, and 2.5%, respectively. Multivariate analysis showed
that female gender (OR, 1.58; 95% CI, 1.14-2.21) and education below college
level (OR, 1.45; 95% CI, 1.01-2.07) were related to FD. Multivariate analysis
based on age 60 showed female gender as a significant (OR, 2.90; 95% CI, 1.06
7.94) factor in the group >= 60 years. Conclusions: The prevalence of FD was
10.3% in the health check-up population in Korea. Female sex and education below
college level were risk factors for FD. Female sex is a risk factor for FD in old
age, underscoring the need for close attention in this age group.
PMID- 29938464
TI - Factors Predictive of Quality of Life among Breast Cancer Patients
AB - Background: Due to progress in medical care, the number of survivors from cancer
has increased significantlyduring recent years and this raises the question of
the quality of life (QoL), especially of the many women treatedfor a breast
cancer. This paper focuses on correlations of QoL with anxiety and depression on
the one hand and withsocio demographic, anatomo-clinical and therapeutic
parameters on the other. Methods: In this cross-sectional study,seventy patients
were enrolled and filled in two auto-questionnaires, both in validated Arabic
versions: The SF-36 forassessment of QoL and the Hospital Anxiety and Depression
Scale (HAD-S) for evaluation of anxiety and depression.The statistical approaches
used to determine predictive factors were bivariate correlations to determine
relationshipsbetween quantitative variables, and T-tests and one-way Anova to
analyze links between qualitative and quantitativevariables. Results: The QoL of
patients was altered with an SF-36 mean total score of 54.0 +/- 22.7, and the
alterationaffects the different aspects. The mean scores for anxiety and
depression in patients were 6.91 +/- 4.72 and 6.24 +/- 3.88,respectively. The
results of this study suggested an association between the QoL and chemotherapy
(p= 0.014) and itsadverse effects (p=0.01), as well as anxiety (p= 0.0001) and
depressive symptoms (p= 0.0001). Socio-demographicfactors, the stage of the
cancer, and surgery, radiotherapy or hormone therapy did not appear to have
significanteffects. Conclusion: The management of breast cancer patients needs a
collaborative approach between oncologists,gynecologists, psychologist and
psychiatrists.
PMID- 29938465
TI - Factors Affecting Long-Survival of Patients with Esophageal Cancer Using Non
Mixture Cure Fraction Model
AB - Objective: Esophageal cancer (EC) is one of the gastrointestinal malignancies
with a very high morbidity andmortality rate due to poor prognosis. This study
aims to assess the effects of risk factors on survival and cure fraction
ofpatients with EC in a population of Iranian patients using a non-mixture cure
fraction model. Methods: This retrospectivecohort study was conducted on 127
patients with EC who were diagnosed during 2009-2010 and were followedup for 5
years in East-Azarbaijan, Iran. Stepwise selection and non-mixture cure fraction
model were used to findthe risk factors of EC survival patients. Results: The
mean (+/-standard deviation) diagnosis age of the EC was66.92(+/-11.95). One,
three and five-year survival probabilities were 0.44 (95% confidence interval
(CI): 0.36-0.54),0.2 (95% CI: 0.14-0.28) and 0.13 (95% CI: 0.08-0.2)
respectively. Female sex (Estimate=-0.99; 95% confidence interval(CI): -1.41,
0.58; p-value<0.001), low level socioeconomic status (Estimate=0.39; 95%CI:
0.12,0.66; p-value=0.043),the group who did not do esophagectomy surgery
(Estimate=0.58; 95%CI: 0.17,0.99; p-value=0.005) and unmarriedgroup
(Estimate=0.58; 95%CI: 0.11-1.05; p-value=0.015) were found as the significant
predictor of survival andcure fraction of the EC patients. Population cure rate
was 0.11 (95%CI: 0.07-0.19) and Cure fraction was estimated5.11 percent.
Conclusion: This study found gender, socioeconomic status, Esophagectomy surgery
and marital statusas the potential risk factors for survival and cure fraction of
Iranian EC patients. Moreover, non- mixture cure fractionprovides more accurate
and more reliable insight into long-term advantages of EC therapy compared to
standard classicsurvival analysis alternatives.
PMID- 29938466
TI - Potential Prophylactic Effect of Berberine against Rat Colon Carcinoma Induce by
1,2-Dimethyl Hydrazine
AB - Introduction: Colon Cancer remains one of the major worldwide causes of cancer
related morbidity and mortalityin both genders. Berberine (BBR), a major
component of alkaloids that possess a variety of pharmacological
properties.Objective: This study shows the ameliorating roles of berberine on 1,2
Di methyl hydrazine (DMH) induced coloncancer in male Swiss albino rats. Methods:
The rats were segregated into four groups: group 1, control rats; group2, rats
were orally received berberine (75 mg/kg b.wt./day) daily for ten weeks; group
3,rats were subcutaneouslyinjected with DMH (20 mg/kg b.wt) once a week for 8
weeks ,group 4, rats were treated firstly with berberine fortwo weeks before DMH
intoxication and concurrently with DMH over 8 weeks. Result: DMH injection
decreasedthe antioxidants levels (GSH and SOD) and increased inflammatory markers
(MPO, MAPK and COX-2). Moreover,it downregulated apoptotic markers (Caspase-3 and
P53) expression that confirmed by colon cell proliferation. Theprophylactic
effect of berberine was noticed as its pre-and co-administration increased
antioxidants status and apoptoticmarkers expression that associated with
inflammatory markers down-regulation with absence of proliferated coloncells.
Conclusion: Therefore, the overall findings proved that the anti-proliferative
effect of berberine return to itsantioxidants and anti-inflammatory properties
that activated the programmed cell death process.
PMID- 29938467
TI - Body-Mind Healing Strategies in Patients with Cancer: a Qualitative Content
Analysis
AB - Background: Cancer is a major health problem around the world. The use of coping
strategies among patientswith cancer depends on several issues. This study was
conducted to determine coping strategies used by patientswith cancer in south
east Iran. Methods: This study is a conventional, qualitative content analysis
with a descriptiveexplorative approach. Data saturation achieved after
interviewing 13 participants in 15 interviews. Using an in-depthindividual semi
structured approach the participants were asked to narrate their experiences of
strategies that they used tocope with cancer. The following were considered: unit
of analysis, meaning unit, condensation, code, sub-category,category, and main
category. Results: Data analysis led to extraction of two main categories of body
mind healingstrategies: being connected to the body and mindfully reconnected to
the self. The first category was explained withreference to two sub-categories,
being aware of intelligence and body nurturing. The second category was
explainedwith the three sub-categories of using embodying knowledge, living for
the moment, and being connected to nature.Conclusion: According to the results of
this qualitative study, it is possible to form discussion groups with peers or
tohave self-reflective practice learning groups to reflect patients' questions
and strategies that they use for body-mindhealing.
PMID- 29938468
TI - Evaluation of Anticancer Activity of Camellia Sinensis in the Caco-2 Colorectal
Cancer Cell Line
AB - Background: Colorectal cancer (CRC) is widespread across the world. While
conventional anticancer treatmentscan help the affected patients, cells of vital
organs such as the kidney, lungs, bladder and nervous system maysuffer from side
effects of chemotherapeutic drugs, so that it is necessary to search for
alternatives. From ancienttimes, attention has focused on medicinal plants and
natural products. In the current work, Camellia sinensis, whoseleaves are used to
produce green tea was evaluated for anticancer effects in cell culture. Materials
and Methods:A hydroalcoholic extract of Camellia sinensis young leaves was
prepared by percolation and compared with Cisplatinas a known anticancer drug for
effects on two cell lines: Caco-2, colon carcinoma cells, and mouse normal
fibroblasts(L929). Cytotoxicity of 50, 100, 200, 400 and 800 MUg/ml of Camellia
sinensis extract was evaluated by MTT assay andaquaporin 5 (AQP5), detected as a
biomarker for surviving cells using immunofluorescence microscopy. Results:
MTTassays with hydroalcoholic extract of Camellia sinensis showed considerable
inhibition of growth of Caco-2 cells,significant at 800 MUg/ml (P<0.05), with
little effect on L929 cells. Levels of aquaporin 5 protein decreased in Caco
2cell culture following green tea extract treatment. Conclusion: According to the
results of the current study, Camelliasinensis is a medicinal plant with potent
anticancer influence which might be specific.
PMID- 29938469
TI - Muslim Husbands' Roles in Women's Health and Cancer: The Perspectives of Muslim
Women in Indonesia
AB - Background: Breast and cervical cancers are the most common cause of cancer death
among women in the world.These cancers are detectable early, however only a few
women participate in cancer screening especially in developingcountries,
including Indonesia. Family, culture and religion can influence why women have
screening. Husbands, inMuslim families have a significant role in the family's
health including their wife's reproductive health. However,information about
Muslim husbands' roles in wife's health especially cancer is limited. Objective:
The purpose ofthis study was to determine Muslim husband's roles in women's
health and cancer from the perspectives of Muslimwomen. Methods: This study was a
qualitative study using a descriptive exploratory approach. Purposive samplingwas
used to recruit 20 Muslim women, 10 from urban areas and 10 from rural areas of
West Java Province, Indonesia.Women were interviewed using a semi-structured
interview schedule. Data from the interviews were analyzed usingthe Comparative
Analysis for Interview technique. Results: The study found two main themes
emerged from the analysis:Muslim husbands' extensive roles in promoting women's
health and Husbands' have limited actions with regard tocancer screening. This
study also found similarities between rural and urban women's opinions that in
general husbandsactively supported promoting women's health. Conclusion: Muslim
husbands focused on encouraging women tohave healthy lifestyles, however, a lack
of support from husbands related to cancer screening. This behaviour couldbe a
hindrance to Muslim women's participation in prevention and the early detection
of cancer. There is a need toimprove Muslim husbands' awareness in women's
cancer.
PMID- 29938470
TI - HPV Could be a Potential Factor of Survival in Laryngeal Cancer: a Preliminary
Study in Mexican Patients
AB - Introduction: In Head and Neck (HN) cancer, the High-Risk Human Papillomavirus
(hr HPV) infection has beenassociated in about 40% of these tumors. The hr HPV
infection is one of the etiological factors of several epithelialtumors; however,
its association with the prognosis has not yet been established for patients with
Laryngeal SquamousCell Carcinoma (LSCC). On the other hand, Epidermal Growth
Factor Receptor (EGFR) is a molecular marker widelystudied in cancer and its
overexpression has been associated with poor prognosis in some types of cancer,
includingthe HN cancer. In the present study, we analyzed EGFR expression and HPV
detection in a cohort of Mexican patientswith LSCC and define their association
with clinical-pathological and survival parameters. Methods: EGFR
expressionanalysis was performed by immunohistochemistry assay. A tissue array
was constructed based on 30 paraffin-embeddedtissue samples. HPV detection was
performed by PCR. The results were then compared with the clinical
pathologicalvariables and outcome measures (Kaplan Meier and Cox analysis).
Results: High expression of EGFR was observedin 43% of the samples and 20% of HPV
detection. The statistical analyses provided evidence of disassociation
betweenclinical-pathological parameters and EGFR expression, but there was an
association with poor prognosis. Interestingly,HPV detection is slightly
associated with good prognosis. Conclusion: Both, EGFR overexpression and HPV
presencecould be associated with an unfavorable prognosis in patients with LSCC,
independently of other clinical-pathologicalfactors.
PMID- 29938471
TI - An Interleukin-6 Single Nucleotide Polymorphism and Susceptibility to Prostate
Adenocarcinoma and Bone Metastasisin an Iranian Population
AB - Objective: Interleukin-6 (IL-6) is an inflammatory cytokine shown to be a strong
factor for growth, proliferation andmetastasis with many malignancies. The
promoter single nucleotide polymorphism (SNPs) -174G>C (rs1800795) canalter the
transcriptional pattern of this gene. The present study was aimed at assessing
effects of the IL-6 (rs1800795)SNP on risk of benign prostate hyperplasia (BPH)
and prostatic adenocarcinoma (PCa). Methods: The project wasperformed on 112 men
with PCa, 118 with BPH and 250 healthy controls. After DNA extraction, genotyping
of IL-6(rs1800795) was performed using PCR TaqMan Allelic Discrimination (ABI
MGB). Results: The G allele frequencyfor rs1800795 of the IL-6 gene was 74.1%,
68.6% and 67% in PCa patients, BPH patients and healthy men, respectively.PCa and
control groups showed significant differences (P =0.030, OR = 1.73, 95% CI: 1.05
2.21). The GG genotypewas more frequent in the PCa group, whereas the GC genotype
was more common in the BPH in comparison to othergroups. Conclusion: The current
study identified IL-6 -174G>C (rs1800795) as a significant predictor of
susceptibilityfor prostate cancer and bone metastasis in a northwest Iranian
population.
PMID- 29938472
TI - HER2 Expression Status and Prognostic, Diagnostic, and Demographic Properties of
Patients with Gastric Cancer: a Single Center Cohort Study from Iran
AB - Background: The fourth most prevalent cancer worldwide and a major cause of death
in developing countries isgastric cancer (GC). Human epidermal growth factor
receptor 2 (HER2), is a proto-oncogene expressed in differentsolid tumors. This
study aimed to evaluate possible associations of HER2 expression status with
survival rate, age,sex, tumor grade, histopathological type, and primary tumor
location in patients with GC. Methods: Subjects wereenrolled in this cohort study
after consideration of inclusion and exclusion criteria. Biopsy specimens were
stained usingimmunohistochemistry. Samples with a score of 3+ were considered to
exhibit HER2 overexpression. The mentionedvariables were extracted from patients'
files as well as by clinical evaluation. The Kaplan-Meier method was appliedfor
analyzing the survival rate and Chi square for possible factor associations.
Results: A total of 210 patients (25.2%female and 74.8% male) were enrolled. In a
5-year follow-up (adherence rate: 45.7%), the average survival was 9.4+/
10.9months. HER2 overexpression was evident in 24%. There was no statistically
significant association found betweenHER2 expression and primary tumor location
(p-value=0.63), histopathological type (p-value=0.72), or tumor grade(p
value=0.051). Furthermore, no statistically significant links were apparent with
tumor grade in either male or femalegroups as well as patients aged >=60 and ?60
years (all p-values >0.05). Moreover, no statistically significant associationwas
detected between HER2 expression status (p-value=0.88), sex (p-value=0.31), and
age (p-value=0.055) with patientsurvival. Conclusions: No statistically
meaningful association was found between all parameters examined and
HER2expression status. Divergence of the results from earlier studies might be
due to genetic variation. Thus, performing ameta-analysis on certain races might
be helpful for clarification.
PMID- 29938473
TI - Willingness to Pay for Colorectal Cancer Screening and Effect of Copayment in
Southern Thailand
AB - Background: The incidence rate of colorectal cancer in Thailand is increasing.
Hence, the nationwide screeningprogramme with copayment is being considered.
There are two proposed screening alternatives: annual fecalimmunochemical test
(FIT) and once-in-10-year colonoscopy. A copayment for FIT is 60 Thai baht (THB)
per test(~ 1.7 USD); a copayment for colonoscopy is 2,300 THB per test (~ 65.5
USD). Methods: The willingness to pay(WTP) technique, which is theoretically
founded on a cost-benefit analysis, was used to assess an effect of copayment
onthe uptake. Subjects were patients aged 50-69 years without cancer or screening
experience. WTP for the proposedtests was elicited. Results: Nearly two thirds of
subjects were willing to pay for FIT. Less than half of subjects werewilling to
pay for colonoscopy. Among them, median WTP for both tests was greater than the
proposed copayments.In a probit model, knowing CRC patient and presence of
companion were associated with non-zero WTP for FIT.Presence of companion,
female, and family history of cancer were associated with non-zero WTP for
colonoscopy.After adjustment for starting price in the linear model, marital
status, drinking behavior, and risk attitude were associatedwith WTP. None of
factors was significant for colonoscopy. Uptake decreased as levels of copayment
increased.At proposed copayments, the uptake rates of 59.8% and 21.6% were
estimated for colonoscopy and FIT respectively.The demand for FIT was price
inelastic; the demand for colonoscopy was price elastic. Estimates of optimal
copaymentwere 62.1 THB for FIT and 460.2 THB for colonoscopy. At the optimal
copayment, uptake rates would be 59.8%for FIT and 42.3% for
colonoscopy.Conclusion(s): More subjects were willing to pay for FIT than for
colonoscopy(59.0% versus 46.5%). The estimated uptake rates were 59.8% and 21.6%
for colonoscopy and FIT at the proposedcopayments.
PMID- 29938474
TI - Frequency of ALK Rearrangement by FISH Testing and its Correlation with ALK-IHC
in Adenocarcinoma of Primary Lung Origin
AB - Anaplastic lymphoma kinase (ALK) gene can be oncogenic either by forming fusion
with other genes, amplificationof the gene or by having mutations. ALK
rearrangement can either be detected by standard "fluorescence in
situhybridization (FISH)" or "immunohistochemistry (IHC)". Objective of this
study was to record the prevalence ofALK rearrangement in adenocarcinoma of
Primary Lung origin and compare it with ALK-IHC staining. Data of64 patients of
lung adenocarcinoma from 2015-2017 was analyzed. All of the FFPE biopsies were
tested for EGFR(qPCR) followed by ALK rearrangement (by FISH and IHC) on EGFR
negative samples. Out of 64 samples, 21.8%(14) showed EGFR mutations and 14%
(7/50) were positive for ALK rearrangement when checked by FISH. In IHCtesting
for ALK (FISH positive) 8% (4/50) showed positivity. In conclusion ALK-FISH
positive cases are higher thanother studies likely due to the relatively small
sample size. FISH testing was found to be more sensitive than IHC; onereason may
be the low level of ALK. Our study warrants that currently FISH remains the gold
standard for screeningof ALK gene rearrangements.
PMID- 29938475
TI - Emerging viral epidemics and pandemics: What will be the next?
PMID- 29938476
TI - Assessment of serum prolactin levels in patients with systemic lupus
erythematosus.
AB - To determine the relationship between hyperprolactinemia levels and clinical
features of patients with systemic lupus erythematosus (SLE), a descriptive,
correlational and cross-sectional study, was performed in female patients over 18
years old, who attended the Rheumatology Clinic at the Hospital Universitario, in
Maracaibo, Venezuela, from November 2012 to June 2013. They underwent a
comprehensive medical history evaluation, based on interviews and physical
examination, with emphasis on the search for clinical manifestations of lupus
activity. Blood samples were taken in order to determine prolactin levels at the
moment of the patient evaluation. Values from 2.1 to 47.6 ng/mL were considered
as normal. The population was classified into two groups: a group formed by 28
women with lupus crisis and another group formed by 22 patients without crisis.
The average prolactin serum level was 39.0 +/- 59.5 ng/dL for the first group and
14.2 +/- 7.2 ng/dL for the second group, indicating statistical significance (p =
0.044). Patients with lupus crisis had prolactin values higher than those of
asymptomatic patients, although only one-seventh of them had absolute
hyperprolactinemia. All asymptomatic patients had normal levels of prolactin. All
patients with hyperprolactinemia were in lupus crisis.
PMID- 29938478
TI - Lip projection analysis in brachycephalic, dolichocephalic and mesocephalic
individuals of a Mexican population.
AB - The aim of this study was to examine the lip projection of brachycephalic,
dolichocephalic and mesocephalic Mexican patients and to analyze the relationship
between dental protrusion and the lip position, to identify if a labial soft
tissue projection exists and to determine what features predominated in this
study. A total of 120 lateral radiographs of the skull were randomly selected
from patients aged 16-25 years. The linear and angular data were measured, the
values of the upper and lower lip projection relative to Ricketts E-line, Steiner
S-line and Arnett TV-line were collected. The angles to be analyzed were the
nasolabial, mandibular plane and interincisal, and the mentolabial groove depth.
The statistical significance was determined by the Student t-test. A significant
difference between mesocephalic and brachycephalic patients was observed
measuring the angle between the Frankfurt plane and the mandibular plane
(P<0.001). Between dolichocephalic and mesocephalic individuals significant
differences were observed in the lower lip to E-line (P<0.031), lower lip to S
line (P<0.010), the interincisal angle (P<0.032) and the mandibular's plane
(P<0.001). A statistical significant difference was shown between brachycephalic
and dolichocephalic individuals: lower lip to E-line (P<0.001), upper lip to S
line (P<0.037), lower lip to S-line (P<0.001), interincisal angle (P<0.034) and
the angle between the mandibular's plane (P<0.001). Lip soft tissue projection
will depend on the population studied; we found some significant differences when
compared with the cephalometric norms.
PMID- 29938477
TI - PAI-1 haplogenotype confers genetic susceptibility for obesity and
hypertriglyceridemia in Mexican children.
AB - The presence of childhood obesity predisposes to the development of
cardiovascular and metabolic diseases, such as coronary artery disease and type 2
diabetes mellitus, in adulthood. The polymorphisms described in PAI-1 gene have
been linked with obesity and metabolic syndrome in several populations. The aim
of this study was to investigate the association of the -844 G/A (rs2227631),
675 4G/5G (rs1799889) and HindIII C/G (rs757716)PAI-1 polymorphisms with obesity
and dyslipidemia in a sample of Mexican children. A cross-sectional study was
performed in 222 children with an age range between 6-11 years; 104 children were
classified as obese and 118 children with normal-weight. The PAI-1 polymorphisms
were analyzed by PCR-RFLP. Linkage disequilibrium (LD) and haplogenotype analysis
among the three polymorphisms were determined. The results showed significant
associations with obesity of the -844 G/A genotype and the A allele (OR= 2.75,
p<0.001 and OR= 1.76, p=0.01, respectively). The -844 G/A polymorphism was found
in LD with -675 4G/5G PAI-1 polymorphism (D'= 0.77). We found that G-4G-C/A-5G-G
is a risk haplogenotype for obesity [OR=2.6; 95% confidence interval (CI) 1.17
4.22; p= 0.01] and with marginal association with hypertriglyceridemia(OR= 2.6;
95% CI 1.04-6.35; p= 0.05). The G-4G-C/A-5G-G PAI-1 haplogenotype may be a
genetic marker of susceptibility for obesity and hypertriglyceridemia in Mexican
children.
PMID- 29938479
TI - Effect of seminal hyperviscosity on acrosomal integrity and sperm motility before
and after cryopreservation.
AB - Semen cryopreservation is a useful tool in assisted reproduction, which may have
impact on sperm characteristics during freezing and thawing. The aim of this
study was to assess the integrity of the acrosome and motility of cryopreserved
and thawed spermatozoos in hyperviscous and no viscous samples. In semen samples
spermiogram, glandular markers, acrosome integrity, culture and the levels
markers accessory glands were measured. Each aliquot of semen was immersed in
cryoprotectant and maintained in a commercial freezer at -196 degrees C. After
30 days, these were thawed and in the cell pellet resuspended, spermatic motility
and acrosomal integrity were evaluated. In thawed samples, there were significant
decreases in progressive motility (p <0.05), vitality (p <0.005) and acrosome
integrity (p <0.05) with respect to fresh sperm, this decline was most evident in
hyperviscous samples. The viscosity of fresh semen was inversely related to
motility and acrosome integrity before and after freezing (p <0.05). Twenty semen
samples showed the presence of microorganisms and C. trachomatis IgA antibodies,
of which fifteen showed hyperviscosity. Biochemical analysis demonstrated that
semen samples with low levels of citric acid had less acrosomal integrity both
before and after freezing (p <0.05). The viscoelasticity and citric acid levels
are associated with prostate dysfunction, low sperm motility and premature
acrosome reaction, which can reduce the fertilizing capacity of sperm. The
etiology of hyperviscosity remains complex; however, to preserve motility and
acrosome integrity, its causes must be investigated previously in the seminal
samples to be subjected to cryopreservation.
PMID- 29938480
TI - Improvement in mood, oxidative stress, fatigue, and insomnia following
supplementary management with Robuvit(r).
AB - BACKGROUND: Oxidative stress (OS) plays a substantial role in inflammatory and
neurodegenerative diseases, causing cellular damage and mitochondrial
dysfunction. OS also contributes to aging and severe neural disorders such as
Alzheimer's and Parkinson's diseases. Previous registries have documented a
reduction in OS levels with Robuvit(r) (Horphag Research, Ltd.), an extract from
wood of the French oak (Quercus robur) that provides a decrease of OS as well as
relief from chronic fatigue syndrome. The aim of the present registry was to
investigate the influence of Robuvit(r) on a group of subjects presenting with
mood disorders, oxidative stress, fatigue, and insomnia. METHODS: Forty patients
were recruited from a selection of patients with high OS levels as assessed with
the d-ROMs test. Twenty-two subjects formed the control group following the
standard management plan. The remaining 18 subjects formed the Robuvit(r)
supplementation group. They received three capsules of Robuvit(r) 100 mg per day,
for 8 weeks. RESULTS: Tolerability to the supplementation with Robuvit(r) was
overall good, and no safety concerns were raised. Mood tests showed a significant
general improvement in 13 out of 16 items of the BMIS (P<0.05) in the active
treatment group. Oxidative stress levels decreased significantly with Robuvit(r)
supplementation after 4 and 8 weeks. Fatigue and insomnia score were also
significantly better in supplemented subjects (P<0.05). No changes were observed
in controls. CONCLUSIONS: The observed decrease in OS levels in our patients is
probably the result of the antioxidative activity of Robuvit(r), and, more
precisely, of its active metabolites, the urolithins and ellagic acid.
PMID- 29938481
TI - Endoscopic washout for medically refractory cerebral ventriculitis.
PMID- 29938482
TI - Simultaneous supratentorial anaplastic and infratentorial low grade ependymomas
with distinct genetic profiles.
PMID- 29938483
TI - Effect of cerebellar adrenomedullin during acute stress.
AB - Adrenomedullin (AM) is a peptide involved in cardiovascular regulation. In the
cerebellum, the density of AM receptors is altered during hypertension,
suggesting a possible role of cerebellar adrenomedulinergic system in the
regulation of blood pressure (BP). The aim of this study was to evaluate the
functional role of AM during acute stress, by in situ administration of AM into
the cerebellar vermis in rats. Adult normotensive Wistar Kyoto (WKY) and Sprague
Dawley (SD) rats and spontaneously hypertensive rats (SHR), were anesthetized and
later, their cerebellar vermis cannulated. Footshock was used as stressor.
Animals were divided into groups that received either AM (0.2 and 200 pmol/5MUL)
or vehicle (physiological saline, 5MUL). The BP was determined, using noninvasive
digital plethysmography, before and after treatment, followed by the application
of footshock (100V, 5 Hz, 10 msec, for 4 minutes). The results show that
microinjection of AM (0.2 and 200 pmol) in situ into the cerebellar vermis in SD,
WKY and SHR rats, significantly decreased the pressor response induced by
footshock stress, suggesting that the hypotensive action is mediated through
regulation of sympathetic outflow. Taken together, our results demonstrate a role
of cerebellar AM in the regulation of cardiovascular response to stress.
PMID- 29938484
TI - Biochemical and nutritional factors associated with blood viscosity in adults
living in a mountain chain, (Imbabura), Ecuador.
AB - The association of blood viscosity (BV) with hypertension and diabetes mellitus
type 2 indicates that it should be considered, especially in populations living
in mountain chains where the hemoglobin and hematocrit values are higher. In
fact, this work analyzed the association of BV with nutritional and biochemical
risk factors in the development of cardio metabolic diseases in healthy adults
(20-60 years old; 46.39% female and 53.61% male) living in the urban Ecuadorian
sierra. The body mass index (BMI) was calculated. The body fat percentage, body
water percentage, waist circumference (WC) and blood pressure were measured.
Determinations of biochemical and hematological parameters were performed using
established methodologies and a validated formula was used to determine the BV.
Hyperviscosity (HV) was present in 14.76% of the population: 10.46% men, 4.3%
women. In this group, 42.8% showed metabolic syndrome (MS) against 33% in the
normoviscosity group (NV). Uric acid (UA) was observed statistically higher in HV
and NV with MS groups. A simple positive linear correlation was found between
glucose (GLU) and triglycerides (TRI) concentrations and BV in HV without MS
group. The multiple linear regression analysis indicated that GLU, UA and
systolic pressure influence to increase BV in the HV without MS group. Glucose
concentration and percentage of water, independently influence the BV in the NV
without MS group. The increase in GLU and UA concentrations are the most
influencing factors on BV in this population.
PMID- 29938485
TI - Control of Concentration of Nonhydrogen-Bonded Hydroxyl Groups in Polymer
Dielectrics for Organic Field-Effect Transistors with Operational Stability.
AB - Poly(4-vinylphenol) (PVP) is a promising gate dielectric material for organic
field-effect transistors (OFETs) and circuits fabricated on plastic substrates.
Thermal cross-linking of PVP with a cross-linker, such as poly(melamine- co
formaldehyde) methylated (PMF), at a high temperature (above 170 degrees C) is
widely considered an effective method to remove residual hydroxyl groups that
induce polarization effects in the dielectric bulk. However, the threshold
voltage shift in transfer characteristics is still observed for an OFET with a
PVP-PMF dielectric when it is operated at a slow gate voltage sweep rate. The
present study examines the cause of the undesired hysteresis phenomenon and
suggests a route to enable a reliable operation. We systematically investigate
the effect of the PVP-PMF weight ratio and their annealing temperature on the
transfer characteristics of OFETs. We discover that the size of the hysteresis is
closely related to the concentration of nonhydrogen-bonded hydroxyl groups in the
dielectric bulk and this is controlled by the weight ratio. At a ratio of 0.5:1,
a complete elimination of hysteresis was observed irrespective of the annealing
temperature. We finally demonstrate a highly reliable operation of small-molecule
based OFETs fabricated on a plastic substrate at a low temperature.
PMID- 29938486
TI - Nanostructured CuO/C Hollow Shell@3D Copper Dendrites as a Highly Efficient
Electrocatalyst for Oxygen Evolution Reaction.
AB - Adoption of bare metal oxides as catalytic materials shows inferior
electrochemical activity because of their poor electrical conductivity. Although
synthetic strategies for the employment of conductive substrates are well
established, the rational design and fabrication of hollow metal oxides
nanostructures on the robust matrix with a high surface area and conductivity
remains challenging. In the present research work, a strategy that transforms a
metal-organic framework thin layer into a nanostructured CuO/C hollow shell to
coat on the 3D nano-dendritic Cu foams as an electrode was successfully
developed. This electrode is claimed to provide an extraordinary electrocatalysis
for oxygen evolution reaction (OER) in alkaline media. The hierarchical complex
presents fast electronic transmission networks and rich redox sites, leading to
the significant enhancement in electrocatalytic OER efficiency. Furthermore, the
spherical porous structure and robust architecture facilitate the high-speed
diffusion of O2 bubbles in a long-term operation. The results of this study may
serve as a reference for the designing of novel class 3D metal/metal oxide
hierarchical structures for gas-involved (i.e., O2, H2, and CO2) electrocatalytic
applications and beyond.
PMID- 29938487
TI - Microelectromechanical Systems from Aligned Cellulose Nanocrystal Films.
AB - Microelectromechanical systems (MEMS) have become a ubiquitous part of a
multitude of industries including transportation, communication, medical, and
consumer products. The majority of commercial MEMS devices are produced from
silicon using energy-intensive and harsh chemical processing. We report that
actuatable standard MEMS devices such as cantilever beam arrays, doubly clamped
beams, residual strain testers, and mechanical strength testers can be produced
via low-temperature fabrication of shear-aligned cellulose nanocrystal (CNC)
films. The devices had feature sizes as small as 6 MUm and anisotropic mechanical
properties. For 4 MUm thick doubly clamped beams with the CNC aligned parallel to
the devices' long axes, the Young's moduli averaged 51 GPa and the fracture
strength averaged 1.1 GPa. These mechanical properties are within one-third of
typical values for polysilicon devices. This new paradigm of producing MEMS
devices from CNC extracted from waste biomass provides the simplicity and
tunability of fluid-phase processing while enabling anisotropic mechanical
properties on the order of those obtained in standard silicon MEMS.
PMID- 29938488
TI - Enhanced Conductivity of Anion-Exchange Membrane by Incorporation of Quaternized
Cellulose Nanocrystal.
AB - High ion conductivity of anion-exchange membrane is essential for the operation
of alkaline anion-exchange membrane fuel cell. In this work, we demonstrated an
effective strategy to enhance the conductivity of anion-exchange membrane (AEM),
by incorporation of quaternized cellulose nanocrystal (QCNC) for the first time.
Morphology observation demonstrated a uniform distribution of QCNC within QPPO
matrix, as well as a clear QCNC network, which led to significant enhancement in
hydroxide conductivities of composite membranes, for example, 2 wt % QCNC/QPPO
membrane possessed a conductivity of 160% (60 mS cm-1, @80 degrees C) of that of
QPPO. Furthermore, H2/O2 cell performance of membrane electrode assembly based on
2 wt % QCNC/QPPO AEM showed an excellent peak power density of 392 mV cm-2 at 60
degrees C without back pressure, whereas that of neat QPPO AEM was only 270 mV cm
2.
PMID- 29938489
TI - Thermal O-H Bond Activation of Water As Mediated by Heteronuclear [Al2Mg2O5]*+:
Evidence for Oxygen-Atom Scrambling.
AB - Mechanistic insight into the thermal O-H bond activation of water by the cubane
like, prototypical heteronuclear oxide cluster [Al2Mg2O5]*+ has been derived from
a combined experimental/computational study. Experiments in the highly diluted
gas phase using Fourier transform ion-cyclotron resonance mass spectrometry show
that hydrogen-atom abstraction from water by the cluster cation [Al2Mg2O5]*+
occurs at ambient conditions accompanied by the liberation of an OH* radical.
Because of a complete randomization of all oxygen atoms prior to fragmentation,
about 83% of the oxygen atoms of the hydroxyl radical released originate from the
oxide cluster itself. The experimental findings are supported by detailed high
level quantum chemical calculations. The theoretical analysis reveals that the
transfer of a formal hydrogen atom from water to the metal-oxide cation can
proceed mechanistically via proton- or hydrogen-atom transfer exploiting
different active sites of the cluster oxide. In addition to the unprecedented
oxygen-atom scrambling, one of the more general and quite unexpected findings
concerns the role of spin density at the hydrogen-acceptor oxide atom. While this
feature is crucial for [M-O]+/CH4 couples, it is much less important in the O-H
bond activation of water.
PMID- 29938490
TI - Flexible Narrowband Ultraviolet Photodetectors with Photomultiplication Based on
Wide Band Gap Conjugated Polymer and Inorganic Nanoparticles.
AB - Lightweight and flexible ultraviolet (UV) photodetectors (PDs) have wide
applications and have attracted more attention. PDs using organic and inorganic
nanocomposites as active layers with a photodiode configuration could achieve
photomultiplication and narrowband photoresponse via the control of
microstructure and thickness of active layers. Here, we fabricated flexible UV
PDs on indium tin oxide-coated poly(ethylene terephthalate) substrates with a
nanocomposite active layer composed of ZnO nanoparticles blended with a wide band
gap conjugated polymer, poly[(9,9-dioctylfluorenyl-2,7-diyl)- alt- co
(bithiophene)] (F8T2). As a result of the wavelength-dependent penetration depth
of light in the active layer, the fabricated flexible UV PDs showed two narrow
response peaks at 360 and 510 nm under reverse biases in the external quantum
efficiency (EQE) spectra with full width at half maximum (FWHM) less than 20 nm.
Both responses exhibited greater than 100% EQE, indicating a photomultiplication
effect, whereas the UV response at 360 nm was 10 times stronger under -15 V bias.
The fabricated flexible UV PDs were bent under both tensile and compressive
stress to a curvature of 2.1 cm-1, each with 50 repetitions. The peak specific
detectivity ( D*) only decreased by about 5% in total, the FWHM was well retained
below 20 nm and the response speed remained almost constant after two types of
bending, demonstrating mechanical flexibility and photoresponse stability of the
fabricated flexible UV PDs. The photodiode configuration with nanocomposite
active layers offers a promising route to make flexible and conformable
narrowband, photomultiplication-type photodetectors for modern applications.
PMID- 29938491
TI - In Situ Growth of ZIF-8 on PAN Fibrous Filters for Highly Efficient U(VI)
Removal.
AB - Global environmental challenges especially nuclear pollution pose a great threat
to human health and public safety. Metal-organic frameworks (MOFs) with high
surface area and excellent stability are potential candidates for the remediation
of nuclear pollution. Herein, a ZIF-8-based polyacrylonitrile (PAN) fibrous
filter was prepared by an in situ hydrothermal treatment of fibrous filters
consisting of PAN, poly(vinylpyrrolidone) (PVP), and zinc ions with an
electrospinning method. In the process of hydrothermal treatment, PVP can be
extracted from the PAN nanofibers and result in porous structures. Benefiting
from these porous structures, the in situ ZIF-8/PAN filters demonstrated a high
adsorption capacity of U(VI) (530.3 mg g-1 at pH = 3.0). The extended X-ray
absorption fine structure revealed that the adsorption mechanism demonstrated
surface complexation between U(VI) and 2-methylimidazole. Furthermore, the
adsorption device was fabricated, and the dynamic adsorption shows that in situ
ZIF-8/PAN is a promising material for treating the nuclear wastewater. The
present work may provide a new strategy to fabricate MOFs into functional devices
to remediate the increasing global environmental concerns.
PMID- 29938492
TI - Detection of Bisphenol A Using DNA-Functionalized Graphene Field Effect
Transistors Integrated in Microfluidic Systems.
AB - Bisphenol A (BPA) detection has attracted much attention recently for its
importance to food safety and environment. The DNA-functionalized solution-gated
graphene transistors are integrated in microfluidic systems and used for
recycling detections of BPA for the first time. In the presence of BPA, both
single- and double-stranded DNA molecules are detached and released from the
graphene surface in aqueous solutions, leading to the change of device electrical
performance. The channel currents of the devices change monotonically with the
concentration of BPA. Moreover, the devices modified with double-stranded DNA are
more sensitive to BPA and show the detection limit down to 10 ng/mL. The highly
sensitive label-free BPA sensors are expected to be used for convenient BPA
detections in many applications.
PMID- 29938493
TI - O-Glycosylation Enabled by N-(Glycosyloxy)acetamides.
AB - A novel glycosylation protocol has been established by using N
(glycosyloxy)acetamides as glycosyl donors. The N-oxyacetamide leaving group in
donors could be rapidly activated in the presence of Cu(OTf)2 or SnCl4 under
microwave irradiation. This glycosylation process afforded the coupled products
in high yields, and the reaction enjoyed a broad substrate scope, even for
disarmed donors and hindered acceptors. The easy availability of the donors, the
high stability of N-(glycosyloxy)acetamides, and the small leaving group make
this method very practical.
PMID- 29938494
TI - Cyclic Regulation of the Sulfilimine Bond in Peptides and NC1 Hexamers via the
HOBr/H2Se Conjugated System.
AB - The sulfilimine bond (-S?N-), found in the collagen IV scaffold, significantly
stabilizes the architecture via the formation of sulfilimine cross-links.
However, precisely governing the formation and breakup process of the sulfilimine
bond in living organisms for better life functions still remains a challenge.
Hence, we established a new way to regulate the breaking and formation of the
sulfilimine bond through hydrogen selenide (H2Se) and hypobromous acid (HOBr),
which can be easily controlled at simulated physiological conditions. This novel
strategy provides a circulation regulation system to modulate the sulfilimine
bond in peptides and NC1 hexamers, which can offer a substantial system for
further study of the physiological function of collagen IV.
PMID- 29938495
TI - The Effects of Immune Modulators on Amodiaquine-Induced Liver Injury.
AB - If idiosyncratic drug-induced liver injury (IDILI) is immune mediated, then it is
logical that immune modulators may be able to affect liver injury caused by a
drug. We have previously shown that modulating the immune system by impairing
programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated
protein 4 (CTLA-4) signaling, both receptors involved in immune tolerance, was
capable of producing an animal model of amodiaquine (AQ) IDILI with
characteristics very similar to IDILI in humans. Other immune modulators may also
increase liver injury caused by drugs that cause IDILI in humans. In this study,
myeloid derived suppressor cells (MDSCs), transforming growth factor beta (TGF
beta), and lymphocyte-activation gene 3 (LAG3) were targeted with antibodies,
with and without PD-1 and CTLA-4 impairment. We found that anti-Gr1 antibodies
used to deplete MDSCs led to a significant increase in AQ-induced liver injury in
wild-type mice; however, the injury was actually less in PD-1-/- mice, with or
without anti-CTLA-4, and it was less than we have previously observed in PD-1-/-
mice combined with anti-CTLA-4 without anti-Gr1. Addition of anti-LAG3 or anti
TGF-beta antibodies produced a small increase ALT in AQ-treated wild-type mice.
There was a significant increase in ALT in PD-1-/- mice co-treated with anti-LAG3
or anti-TGF-beta relative to AQ-treated wild-type mice. In the case of TGF-beta,
this was further increased by the addition of anti-CTLA-4, but if anything, there
appeared to be a paradoxical decrease when anti-CTLA-4 was combined with anti
LAG3. Overall, the results from this study were not always as expected, and they
highlight the complexity of the immune response, in particular immune tolerance,
which appears to be the dominant immune response to drugs that cause IDILI.
PMID- 29938496
TI - Binary Thiolate DNA/Ferrocenyl Self-Assembled Monolayers on Gold: A Versatile
Platform for Probing Biosensing Interfaces.
AB - The properties of DNA self-assembled monolayers (SAMs) have strong influences on
the interfacial DNA-analyte binding behavior, which further affect the
performance of biosensors built upon. In this work, we prepared binary thiolate
DNA/6-ferrocenyl-1-hexanethiol (FcC6SH) SAMs on gold (DNA/FcC6S-Au) for
convenient electrochemical characterization and subsequent data analysis. Our
cyclic voltammetric (CV) studies confirmed that the redox responses of surface
tethered Fc and electrostatically bound [Ru(NH3)6]3+ are capable of providing
quantitative information regarding the DNA film properties, including the surface
density, structural heterogeneity, and molecular orientation under different
preparation and measurement conditions. With the binary thiolate DNA/FcC6S-Au SAM
prepared in the conventional post-assembly exchange protocol as a trial system,
we are demonstrating the capability of introducing redox-active thiols as
passivating and labeling reagents for preparing many other DNA-based biosensing
interfaces via varied assembly steps and under different measurement conditions.
PMID- 29938498
TI - Lipid Bilayer-Enabled Synthesis of Waxberry-like Core-Fluidic Satellite
Nanoparticles: Toward Ultrasensitive Surface-Enhanced Raman Scattering Tags for
Bioimaging.
AB - Herein, we presented waxberry-like core-satellite (C-S) nanoparticles (NPs)
prepared by an in situ growth of satellite gold NPs on spherical phospholipid
bilayer-coated gold cores. The fluidic lipid bilayer cross-linker was reported
for the first time, which imparted several novel morphological and optical
properties to the C-S NPs. First, it regulated the anisotropic growth of the
satellite NPs into vertically oriented nanorods on the core NP surface. Thus, an
interesting waxberry-like nanostructure could be obtained, which was different
from the conventional raspberry-like C-S structures decorated with spherical
satellite NPs. Second, the satellite NPs were "soft-landed" on the lipid bilayer
and could move on the core NP surface under certain conditions. The movement
induced tunable plasmonic features in the C-S NPs. Furthermore, the fluidic lipid
bilayer was capable of not only holding an abundance of reporter molecules but
also delivering them to the hotspots at the junctions between the core and
satellite NPs, which made the C-S NPs an excellent candidate for preparing
ultrasensitive surface-enhanced Raman scattering (SERS) tags. The bioimaging
capabilities of the C-S NP-based SERS tags were successfully demonstrated in
living cells and mice. The developed SERS tags hold great potential for
bioanalysis and medical diagnostics.
PMID- 29938497
TI - Profiles of Volatile Compounds in Blackcurrant ( Ribes nigrum) Cultivars with a
Special Focus on the Influence of Growth Latitude and Weather Conditions.
AB - The volatile profiles of three blackcurrant ( Ribes nigrum L.) cultivars grown in
Finland and their responses to growth latitude and weather conditions were
studied over an 8 year period by headspace solid-phase microextraction (HS-SPME)
followed by gas-chromatographic-mass-spectrometric (GC-MS) analysis. Monoterpene
hydrocarbons and oxygenated monoterpenes were the major classes of volatiles. The
cultivar 'Melalahti' presented lower contents of volatiles compared with 'Ola'
and 'Mortti', which showed very similar compositions. Higher contents of
volatiles were found in berries cultivated at the higher latitude (66 degrees
34' N) than in those from the southern location (60 degrees 23' N). Among the
meteorological variables, radiation and temperature during the last month before
harvest were negatively linked with the volatile content. Storage time had a
negative impact on the amount of blackcurrant volatiles.
PMID- 29938499
TI - Discerning Black Phosphorus Crystal Orientation and Anisotropy by Polarized
Reflectance Measurement.
AB - Strong in-plane anisotropy of atomic layer and thin-film black phosphorus (P)
offers new device perspectives and stimulates increasing interest and
explorations, where precisely determining the black P crystal orientation and
anisotropic axes is a necessity. Here, we demonstrate that the crystal
orientation and intrinsic in-plane optical anisotropy of black P crystals in a
broad thickness range (from ~5 to ~300 nm) can be directly and precisely
determined, by polarized reflectance measurement alone, in visible range.
Combining experiments with modeling of optical anisotropy and multilayer
interference effects, we elucidate the underlying principles and validate these
measurements. The polarized reflectance method is not only easy to implement but
also deterministic, nondestructive, and effective for both on-substrate and
suspended black P atomic layers and thin films.
PMID- 29938500
TI - Tunable Electron and Hole Injection Enabled by Atomically Thin Tunneling Layer
for Improved Contact Resistance and Dual Channel Transport in MoS2/WSe2 van der
Waals Heterostructure.
AB - Two-dimensional (2D) material-based heterostructures provide a unique platform
where interactions between stacked 2D layers can enhance the electrical and opto
electrical properties as well as give rise to interesting new phenomena. Here,
the operation of a van der Waals heterostructure device comprising of vertically
stacked bilayer MoS2 and few layered WSe2 has been demonstrated in which an
atomically thin MoS2 layer has been employed as a tunneling layer to the
underlying WSe2 layer. In this way, simultaneous contacts to both MoS2 and WSe2
2D layers have been established by forming a direct metal-semiconductor to MoS2
and a tunneling-based metal-insulator-semiconductor contacts to WSe2,
respectively. The use of MoS2 as a dielectric tunneling layer results in an
improved contact resistance (80 kOmega MUm) for WSe2 contact, which is attributed
to reduction in the effective Schottky barrier height and is also confirmed from
the temperature-dependent measurement. Furthermore, this unique contact
engineering and type-II band alignment between MoS2 and WSe2 enables a selective
and independent carrier transport across the respective layers. This contact
engineered dual channel heterostructure exhibits an excellent gate control and
both channel current and carrier types can be modulated by the vertical electric
field of the gate electrode, which is also reflected in the on/off ratio of 104
for both electron (MoS2) and hole (WSe2) channels. Moreover, the charge transfer
at the heterointerface is studied quantitatively from the shift in the threshold
voltage of the pristine MoS2 and the heterostructure device, which agrees with
the carrier recombination-induced optical quenching as observed in the Raman
spectra of the pristine and heterostructure layers. This observation of dual
channel ambipolar transport enabled by the hybrid tunneling contacts and strong
interlayer coupling can be utilized for high-performance opto-electrical devices
and applications.
PMID- 29938501
TI - Internal Calibration Potentiometric Aptasensors for Simultaneous Detection of
Hg2+, Cd2+, and As3+ Based on a Screen-Printed Carbon Electrodes Array.
AB - An all-solid-state potentiometric aptasensor array based on a multichannel
disposable screen-printed carbon electrode (SPCE) was demonstrated for the
simultaneous detection of Hg2+, Cd2+, and As3+ by open circuit potential (OCP)
technology. The potential of the channel with an internal calibration DNA
sequence (IC-DNA) was employed as the internal calibration potential (ICP) to
subtract the background signal generated by the detection system, providing a
built-in correction methodology. As a result, the developed aptasensor array
showed high sensitivity and accuracy for detecting Hg2+, Cd2+, and As3+ without
mutual interference or interference from other ions. The linear response ranged
from 2.5 pM to 2.5 MUM, and the detection limits for Hg2+, Cd2+, and As3+ were
2.0, 0.62, and 0.17 pM, respectively. Furthermore, the potentiometric aptasensor
array was successfully applied for the simultaneous detection of three ions in
real samples. The results obtained from the developed approach agreed well with
the results obtained from inductively coupled plasma mass spectrometry.
PMID- 29938502
TI - Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry.
AB - This review is an update on tris(trimethylsilyl)silane, TTMSS, in organic
chemistry, focusing on the advancements of the past decade. The overview includes
a wide range of chemical processes and synthetic strategies under different
experimental conditions, including functional group insertion and
transformations, as well as preparation of complex molecules, natural products,
polymers, surfaces, and new materials. These results reveal how TTMSS has matured
over the past 30 years, and they further establish its value as a free radical
reagent with widespread academic and industrial applications.
PMID- 29938503
TI - PEOz-PEDOT:PSS Composite Layer: A Route to Suppressed Hysteresis and Enhanced
Open-Circuit Voltage in a Planar Perovskite Solar Cell.
AB - The successful commercialization of perovskite solar cells (Pvs-SCs) calls for
the need to find low-temperature processable interlayers with outstanding charge
transport features. In this work, we strategically blend poly(2-ethyl-2
oxazoline) (PEOz) with PEDOT:PSS as the modified hole transport layer (HTL) to
achieve high-efficiency P-I-N CH3NH3PbI3 Pvs-SCs. The PEOz-PEDOT:PSS HTL exhibits
enhanced features over the conventional layer including the following: (1)
promoting perovskite with enlarged grain sizes to decrease the perovskite layer's
recombination, (2) increasing the work function of the HTL, and (3) decreasing
the noncapacitive current in Pvs-SCs. Remarkably, we demonstrate a 17.39% power
conversion efficiency with very low hysteresis and high Voc values of 1.075 V for
Pvs-SCs with PEOz-PEDOT:PSS.
PMID- 29938504
TI - Multipedal DNA Walker Biosensors Based on Catalyzed Hairpin Assembly and
Isothermal Strand-Displacement Polymerase Reaction for the Chemiluminescent
Detection of Proteins.
AB - In this study, two kinds of sensitive biosensors based on a multipedal DNA walker
along a three-dimensional DNA functional magnet particles track for the
chemiluminescent detection of streptavidin (SA) are constructed and compared. In
the presence of SA, a multipedal DNA walker was constructed by a biotin-modified
catalyst as a result of the terminal protection to avoid being digested by
exonuclease I. Then, through a toehold-mediated strand exchange, a "leg" of a
multipedal DNA walker interacted with a toehold of a catalyzed hairpin assembly
(CHA)-H1 coupled with magnetic microparticles (MMPs) and opened its hairpin
structure. The newly open stem in CHA-H1 was hybridized with a toehold of biotin
labeled H2. Via the strand displacement process, H2 displaced one "leg" of a
multipedal DNA walker, and the other "leg" continued to interact with the
neighboring H1 to initiate the next cycle. In order to solve the high background
caused by the hybridization between CHA-H1 and H2 without a CHA-catalyst, the
other model was designed. The principle of the other model (isothermal strand
displacement polymerase reaction (ISDPR)-DNA walker) was similar to that of the
above one. After the terminal protection of SA, a "leg" of a multipedal DNA
walker was triggered to open the hairpin of the ISDPR-H1 conjugated with MMPs.
Then, the biotin-modified primer hybridized with the newly exposed DNA segment,
triggering the polymerization reaction with the assistance of dNTPs/polymerase.
As for the extension of the primer, the "leg" of a multipedal DNA walker was
displaced so that the other "leg" could trigger the proximal H1 to go onto the
next cycle. Due to its lower background and stronger signal, a multipedal DNA
walker based on an ISDPR had a lower limit of detection for SA. The limit of
detection for SA was 6.5 pM, and for expanding the application of the method, the
detections of the folate receptor and thrombin were explored. In addition, these
DNA walker methods were applied in complex samples successfully.
PMID- 29938505
TI - Enhancing the Resolution of Micro Free Flow Electrophoresis through Spatially
Controlled Sample Injection.
AB - Free flow electrophoresis is a versatile technique for the continuous separation
of mixtures with both preparative and analytical applications. Microscale
versions of free flow electrophoresis are particularly attractive strategies
because of their fast separation times, ability to work with small sample
volumes, and large surface area to volume ratios facilitating rapid heat
transfer, thus minimizing the detrimental effects of Joule heating even at high
voltages. The resolution of microscale free flow electrophoresis, however, is
limited by the broadening of the analyte beam in the microfluidic channel, an
effect that becomes especially pronounced when the analyte is deflected
significantly away from its original position. Here, we describe and demonstrate
how restricting spatially the sample injection and collection to the regions
where the gradients in the velocity distribution of the carrier medium are the
smallest allows this broadening effect to be substantially suppressed and hence
the resolution of microscale free flow electrophoresis devices to be increased.
To demonstrate this concept, we fabricated microfluidic free flow electrophoresis
devices with spatially restricted injection nozzles implemented through the use
of multilayer soft-photolithography and further integrated quartz based
observation areas for fluorescent detection and imaging. With these devices, we
demonstrated a 5-fold reduction in the extent of beam broadening relative to
conventional free flow electrophoresis approaches with nonrestricted sample
introduction. The manifold enhancement in the achievable resolution of microscale
free flow electrophoresis devices opens up the possibility of rapid separation
and analysis of complex mixtures.
PMID- 29938506
TI - Rhodamine-Derived Fluorescent Dye with Inherent Blinking Behavior for Super
Resolution Imaging.
AB - Super-resolution microscopy enables imaging of structures smaller than the
diffraction limit. Single-molecule localization microscopy methods, such as
photoactivation localization microscopy and stochastic optical reconstruction
microscopy, reconstruct images by plotting the centroids of fluorescent point
sources from a series of frames in which only a few molecules are fluorescing at
a time. These approaches require simpler instrumentation than methods that depend
on structured illumination and thus are becoming widespread. The functionalized
rhodamine derivative reported in this paper spontaneously converts between a
bright and dark state due to pH-dependent cyclization. At pH 7, less than 0.5% of
the dye molecules are fluorescent at any given time. Blinking occurs on time
scales of seconds to minutes and can therefore be used for single-molecule
localization microscopy without sample treatment or activation. The dye is bright
and straightforward to use, and it is easy to synthesize and functionalize. Thus,
it has potential to become a new and powerful addition to the toolset for super
resolution imaging.
PMID- 29938507
TI - Recent Developments of Stir Bar Sorptive Extraction for Food Applications:
Extension to Polar Solutes.
AB - Stir bar sorptive extraction (SBSE) is a miniaturized and solvent-less sample
preparation method for extraction and concentration of organic compounds from
aqueous samples. The method is based on sorptive extraction, whereby the solutes
are extracted into a polymer, such as polydimethylsiloxane (PDMS), coated on a
stir bar. Using an apolar PDMS coating, SBSE provides high recoveries for apolar
solutes; however, SBSE recoveries for polar solutes are low. Although several
more polar coatings for SBSE were developed, these extraction phases are mostly
not compatible with thermal desorption (TD) and/or have inferior performance
characteristics related to robustness, bleeding, stability, etc. compared to
PDMS. In this perspective, two recently introduced SBSE approaches are described
that can be used to extend the applicability of a PDMS coating to more polar
solutes: (1) SBSE with freeze concentration [ice concentration linked with
extractive stirrer (ICECLES)], which is based on the concentration of analytes by
gradually reducing the phase ratio (sample/extraction phase), and (2) SBSE using
a solvent-swollen PDMS [solvent-assisted SBSE (SA-SBSE)], which is based on a
combination of polarity modification and volume increase by PDMS phase swelling
using certain types of solvents while maintaining the original characteristics of
the PDMS phase.
PMID- 29938508
TI - Near-Infrared Light-Excited Core-Core-Shell UCNP@Au@CdS Upconversion Nanospheres
for Ultrasensitive Photoelectrochemical Enzyme Immunoassay.
AB - A novel photoelectrochemical (PEC) enzyme immunoassay was designed for the
ultrasensitive detection of alpha-fetoprotein (AFP) based on near-infrared (NIR)
light-excited core-core-shell UCNP@Au@CdS upconversion nanospheres. Plasmonic
gold (Au) between the sandwiched layers was not only utilized as an energy
harvester for the collection of the incident light but also acted as an energy
conveyor to transfer the energy from upconversion NaYF4:Yb3+,Er3+ (UCNP) to
semiconductor CdS, thus exciting the efficient separation of electron-hole pairs
by the generated H2O2 of enzyme immunoreaction under the irradiation of a 980 nm
laser. By virtue of high catalytic activity of natural enzymes, gold
nanoparticles heavily functionalized with glucose oxidase (GOx) and polyclonal
anti-AFP antibody were utilized to generate H2O2. A sandwiched immunoreaction was
first carried out in a monoclonal anti-AFP antibody-coated microplate by using an
antibody-labeled gold nanoparticle as secondary antibody. Accompanying the gold
nanoparticle, the carried GOx oxidized glucose in H2O2, thereby resulting in the
enhanced photocurrent via capturing holes on the valence band of CdS to promote
the separation of electron-hole pairs. Under optimum conditions, the NIR light
based PEC immunosensing system exhibited good photocurrent responses toward
target AFP within the dynamic working range of 0.01-40 ng mL-1 at a detection
limit of 5.3 pg mL-1. Moreover, the NIR light-based sensing platform had good
reproducibility and high selectivity. Importantly, good well-matched results
obtained from NIR light-based PEC immunoassay were acquired for the analysis of
human serum specimens by using AFP ELISA kit as the reference.
PMID- 29938509
TI - Identification of Key Root Volatiles Signaling Preference of Tomato over Spinach
by the Root Knot Nematode Meloidogyne incognita.
AB - The root knot nematode, Meloidogyne incognita (Kofoid and White) Chitwood, is a
serious pest of tomato ( Solanum lycopersicum) and spinach ( Spinacea oleracea)
in sub-Saharan Africa. In East Africa these two crops are economically important
and are commonly intercropped by smallholder farmers. The role of host plant
volatiles in M. incognita interactions with these two commodities is currently
unknown. Here, we investigate the olfactory basis of attraction of tomato and
spinach roots by the infective second stage juveniles (J2s) of M. incognita. In
olfactometer assays, J2s were attracted to root volatiles from both crops over
moist sand (control), but in choice tests using the two host plants, volatiles of
tomato roots were more attractive than those released by spinach. Root volatiles
sampled by solid phase microextraction (SPME) fiber and analyzed by gas
chromatography/mass spectrometry (GC/MS) identified a total of eight components,
of which five (2-isopropyl-3-methoxypyrazine, 2-(methoxy)-3-(1
methylpropyl)pyrazine, tridecane, and alpha- and beta-cedrene) occurred in the
root-emitted volatiles of both plants, with three (delta-3-carene, sabinene, and
methyl salicylate) being specific to tomato root volatiles. In a series of
bioassays, methyl salicylate contributed strongly to the attractiveness of
tomato, whereas 2-isopropyl-3-methoxypyrazine and tridecane contributed to the
attractiveness of spinach. M. incognita J2s were also more attracted to natural
spinach root volatiles when methyl salicylate was combined than to spinach
volatiles alone, indicating that the presence of methyl salicylate in tomato
volatiles strongly contributes to its preference over spinach. Our results
indicate that since both tomato and spinach roots are attractive to M. incognita,
identifying cultivars of these two plant species that are chemically less
attractive can be helpful in the management of root knot nematodes.
PMID- 29938510
TI - An Optimized Preparation of 1,1-Dimethylallyl Esters and Their Application to
Solid-Phase Peptide Synthesis.
AB - A one-step preparation of 1,1-dimethylallyl (DMA) esters was optimized for the C
terminal protection of a range of Fmoc-protected amino acids. This preparation is
not sensitive to the scale of reaction and affords the corresponding DMA esters
in 70-99% yield with high regioselectivity. Additionally, these DMA-protected
amino acids were used with the backbone amide linker (BAL) of Albericio and
Barany and found to resist diketopiperazine formation during the synthesis of a
series of tripeptide esters. C-terminal DMA protection is compatible with the BAL
linkage and allows for standard Fmoc-based methods to be used throughout the
synthesis.
PMID- 29938511
TI - Proteomic Analysis and Immuno-Profiling of Eastern India Russell's Viper ( Daboia
russelii) Venom: Correlation between RVV Composition and Clinical Manifestations
Post RV Bite.
AB - The proteomes of Russell's viper venom (RVV) from Burdwan (RVV B) and Nadia (RVV
N), the two districts of West Bengal, eastern India (EI), were investigated by
gel-filtration chromatography (GFC) followed by tandem mass spectrometry of
tryptic fragments of the fractions. A total of 73 and 69 proteins belonging to 15
snake venom protein families were identified in RVV B and RVV N, respectively, by
MS/MS search against Viperidae (taxid 8689) protein entries of the nonredundant
NCBI database. The minor differences in venom composition of both the EI RV were
established unequivocally by their biochemical and pharmacological properties and
by SDS-PAGE, gel filtration chromatography, and LC-MS/MS analyses. The
composition of EI RVVs was well correlated with published reports on the
pathophysiology of RV-envenomed patients from this part of the country. Venom
antivenom cross-reactivity determined by ELISA, Western blotting, and
antivenomics approaches demonstrated poor recognition of low molecular mass (<20
kDa) RVV proteins by commercial polyvalent antivenoms, which was substantiated by
neutralization of RVV enzymes by antivenom.
PMID- 29938512
TI - Bistable Amphoteric Native Defect Model of Perovskite Photovoltaics.
AB - The past few years have witnessed unprecedented rapid improvement of the
performance of a new class of photovoltaics based on halide perovskites. This
progress has been achieved even though there is no generally accepted mechanism
of the operation of these solar cells. Here we present a model based on bistable
amphoteric native defects that accounts for all key characteristics of these
photovoltaics and explains many idiosyncratic properties of halide perovskites.
We show that a transformation between donor-like and acceptor-like configurations
leads to a resonant interaction between amphoteric defects and free charge
carriers. This interaction, combined with the charge transfer from the perovskite
to the electron and hole transporting layers results in the formation of a
dynamic n-i-p junction whose photovoltaic parameters are determined by the
perovskite absorber. The model provides a unified explanation for the outstanding
properties of the perovskite photovoltaics, including hysteresis of J-V
characteristics and ultraviolet light-induced degradation.
PMID- 29938513
TI - Catalytic Enantioselective Allylations of Acetylenic Aldehydes via 2-Propanol
Mediated Reductive Coupling.
AB - Cyclometalated pi-allyliridium C,O-benzoates modified by ( S)-SEGPHOS or ( S)
Cl,OMe-BIPHEP catalyze enantioselective 2-propanol-mediated reductive couplings
of diverse nonmetallic allyl pronucleophiles with the acetylenic aldehyde
TIPSC=CCHO. Absolute stereochemistries of the resulting secondary homoallylic
propargylic alcohols were assigned using Rychnovsky's competing enantioselective
conversion method.
PMID- 29938514
TI - Stereocontrolled Synthesis of Triols Containing Four Asymmetric Centers:
Application of C, O-Chelated Germyl Enolates to a Diastereoselective Aldol
Reaction.
AB - The treatment of alpha,beta-unsaturated ketones with divalent germanium salts
cleanly generated C, O-chelated germyl enolates. The aldol reactions of the
chelated enolates with the aldehydes achieved a high diastereoselectivity in the
construction of the five-membered aldol adducts. Furthermore, the subsequent
transformation of the Ge-C bond in the aldol adduct enabled the stereocontrolled
synthesis of triols bearing four asymmetric centers.
PMID- 29938515
TI - Synthesis of N, N-Alkylated alpha-Tertiary Amines by Coupling of alpha
Aminoalkyltrifluoroborates and Grignard Reagents.
AB - The cross-coupling of alpha-aminoalkyltrifluoroborates and Grignard reagents to
form N, N-substituted alpha-tertiary amines (ATAs) is reported. Key to the
success of this reaction is the unexpected oxidation of the alpha
aminoalkyltrifluoroborate to the corresponding iminium cation by commercially
available Barluenga's reagent. Various Grignard reagents added smoothly, enabling
the synthesis of a variety of ATAs, which are of high value for medicinal
chemistry and drug development. Many of the reported examples are not accessible
by the established methods.
PMID- 29938516
TI - Tumor recurrence after liver transplantation for diffuse biliary papillomatosis
in the absence of invasive carcinoma.
AB - Intraductal papillary neoplasm of the bile duct (IPNB) or biliary papillomatosis
(BP) is a premalignant entity with high risk of malignant transformation. When
the disease extends widely from the intrahepatic to the extrahepatic biliary
tree, liver transplantation (LT) is the only option available. We present the
case of a 43-year-old male who was admitted in our hospital with an acute
cholangitis. He was diagnosed of diffuse biliary and pancreatic papillomatosis.
Firstly, we performed a cephalic pancreaticoduodenectomy, then we completed a
total pancreatectomy, and finally, after confirming the absence of foci of
carcinoma infiltration or lymph nodes involvement, a LT was performed. Foci of
carcinoma infiltration or lymph nodes involvement in the liver were not found.
After a two-year follow-up the patient developed liver recurrence and the biopsy
showed a biliary adenocarcinoma. In 2010, Vibert et al. published a series of
three cases concluding that in the absence of invasive carcinoma and positive
lymph nodes, LT can be performed with success. The present case is the first to
describe recurrence of the disease after LT in the absence of invasive carcinoma
and positive lymph nodes in the literature. When the disease affects widely the
entire biliary duct, small micro-invasive foci may not be detected. Nevertheless,
although we know that it is a recurrent entity, the pathogenesis is unknown, and
we do not know if it is possible that papillomatosis recurs over the new liver.
PMID- 29938517
TI - An Epidemiological Study on Burden of Hearing Loss and Its Associated Factors in
Delhi, India.
AB - INTRODUCTION: Hearing loss is the second most common cause of years lived with
disability (YLD). The present study was conducted with an objective to determine
the prevalence, severity, and sociodemographic correlates of hearing loss among
people aged 3 months and above in selected areas of Delhi, India. MATERIAL AND
METHODS: A community-based cross-sectional study was conducted in selected rural
and urban areas of Delhi among population aged 3 months and above. Of the total
sample size of 664, 85 study subjects (17 households) were taken from the rural
area, and 579 (116 households) were taken from urban areas. The hearing test and
ear examination was carried out using handheld oto-acoustic emission (OAE) in
children <5 years of age and pure tone audiometry in individuals above 5 years of
age. SPSS software was used for data analysis. Chi-square test was used to
analyze difference between proportions. RESULTS: Overall prevalence of hearing
loss was 25.1%. Conductive hearing loss was present among 61 (10.3%) subjects,
mixed hearing loss was found among 5 (0.8%) subjects, and sensorineural hearing
loss among 94 (15.8%) subjects. On OAE, 62 (89.9%) children passed the test, and
7 (10.1%) were referred. Increasing age, female gender, and low education were
significantly associated with hearing loss. CONCLUSION: There was high prevalence
of hearing loss in the study sample. Urgent interventions are required to
identify individuals with hearing loss so that its serious complications can be
reduced.
PMID- 29938518
TI - A Dashboard for Monitoring Opioid-Related Adverse Drug Events Following Surgery
Using a National Administrative Database.
AB - Opioid-related adverse drug events (ORADEs) include a range of complications,
from respiratory arrest to ileus and urinary retention. ORADEs correlate to
morbidity, mortality, and increased costs. The Centers for Medicare & Medicaid
Services database, which represents approximately 35% of hospital discharges. The
authors searched for previously published ICD-9 codes that defined ORADEs. A
group of surgical diagnosis-related groups (DRGs) were selected. Recurring
queries were programmed using these ICD codes and DRGs and used to update an
online dashboard. The dashboard presents an estimate of the burden of ORADEs to
frontline clinicians and hospital leadership and allows users to compare local
data on ORADEs rates to other hospitals. Users are able to refine their search by
surgery type or ORADE type. An interface was created, using national
administrative claims data, to allow hospitals to access their ORADEs and
benchmark local data against national trends.
PMID- 29938519
TI - Hearing Preservation After Translabyrinthine Vestibular Schwannoma Excision:
Audiometry and Electrocochleography Results.
AB - OBJECTIVES: To describe a case of inadvertent hearing preservation following a
classical translabyrinthine resection of a vestibular schwannoma of the internal
auditory canal in an otherwise healthy patient. METHODS: Herein, we describe the
case of an otherwise healthy patient who underwent resection of an
intracanalicular vestibular schwannoma via a translabyrinthine approach.
Furthermore, as part of an ongoing study aimed at characterizing hearing changes
due to intraoperative events, cochlear hair cell and nerve activity were
monitored using electrocochleography throughout surgery. Unexpectedly, the
patient maintained serviceable hearing following surgery. As a result, we are
able to provide electrophysiologic evidence of cochlear hair cell activity at
various stages of this surgery. RESULTS: Hair cell responses across tested
frequencies were detectable prior to and following completion of the
translabyrinthine procedure. Neural integrity of the auditory division of cranial
nerve VIII was maintained throughout. Lastly, postoperative audiometric testing
supported the patient's subjective assertion of serviceable hearing in the
surgical ear. CONCLUSION: Our results suggest that some degree of hair cell and
neural integrity can be maintained throughout the course of the translabyrinthine
approach, and if preservation of the auditory division of cranial nerve VIII is
feasible, a functional amount of hearing preservation is attainable.
PMID- 29938520
TI - Introduction of a Mobile Adverse Event Reporting System Is Associated With
Participation in Adverse Event Reporting.
AB - Physicians underutilize adverse event reporting systems. Web-based platforms have
increased participation; thus, it was hypothesized that a mobile application
would increase adverse event reporting. The authors developed a mobile reporting
application for iOS and Android operating systems and performed a retrospective
review on reporting rates by clinicians in the Department of Anesthesia and
Critical Care. Monthly reporting rates were calculated for the intervention year
and for the 2 prior years (2013-2016). The Wilcoxon rank sum test and chi2 test
were used to evaluate significance. Overall monthly reporting rates for all
clinicians were 15.3 +/- 7 for the first time period, 17.3 +/- 6 for the second
time period, and 27.9 +/- 7 for the third time period ( P = .0035). The majority
of reports in the third time period were submitted using the mobile application
(193/337, 57%, P = .026). Deployment of a mobile application reduced barriers to
adverse event reporting and increased monthly reporting rates for all clinicians.
PMID- 29938521
TI - Hypertrophic Pachymeningitis of the Internal Auditory Canal: A Rare Case of
Unilateral Sudden Sensorineural Hearing Loss.
AB - OBJECTIVES: To describe and increase awareness of a rare cause of unilateral
sudden sensorineural hearing loss. METHODS: Case report and literature review.
RESULTS: We present a 66-year-old female who suffered left-sided sudden
sensorineural hearing loss and dizziness. Diagnostic magnetic resonance imaging
(MRI) did not reveal masses or lesions along the eighth cranial nerve or in the
inner ear. Upon eventual referral to neurotology clinic, hypertrophic
pachymeningitis of her left internal auditory canal and adjacent middle and
posterior fossa dura were identified. The ensuing laboratory workup for
autoimmune and infectious etiology revealed mild elevation of ACE 93 (9-67) but
otherwise normal results. CONCLUSIONS: Idiopathic hypertrophic pachymeningitis is
a diagnosis of exclusion. Neoplastic, infectious, and autoimmune causes must be
ruled out. The prevailing treatment for this condition is high-dose
corticosteroids. This entity should be considered when evaluating MRI scans
obtained in the setting of sudden sensorineural hearing loss.
PMID- 29938522
TI - Number of Unused Medications at the Time of Last Admission: A Prospective
Observational Study in a Single Palliative Care Unit.
AB - BACKGROUND:: Unused medications (UM) are an important issue, with the waste
associated with UM a burden to the health-care system. The aims of this study
were to clarify the amount and costs of UM in patients with advanced cancer at
the time of their last admission to a palliative care unit and to explore the
factors contributing to the cost of UM and how patients dealt with UM. METHODS::
A prospective observational study was conducted in single palliative care unit.
Unused medications were classified into 6 categories and the number and cost of
UM by category calculated per patient. Patients were classified into 2 cost
groups (high and low) based on the total cost of UM, and the number and cost of
UM by category were compared between these 2 groups. RESULTS:: Of 194 consecutive
hospitalized patients, data were analyzed for 90. The mean number and cost of UM
per patient was 440 and US$301, respectively. Opioids accounted for 47% of the
cost of UM. Comparing costs by UM category, the proportion of opioids (51% vs
21%; P < .0001) and oral anticancer drugs (14% vs 3%; P = .02) was higher in the
high- than in the low-cost group. CONCLUSION:: Based on the results of the
present study, the estimated annual waste cost of UM for patients with cancer who
died in Japan was approximately US$110 million. Interventions to educate patients
regarding UM and to eliminate barriers to opioid use may help reduce the cost of
UM, particularly opioids and anticancer drugs.
PMID- 29938523
TI - Spectral Analysis of the Amplified Spontaneous Emission in the Second Positive
System of the N2 Molecule.
AB - The spectrum of the 0-0 band of the [Formula: see text] electronic transition of
the N2 molecule presents a considerable difference in its distribution of
intensities, as a function of the wave number, when the emission spectrum by glow
discharge is compared to an amplified spontaneous emission (ASE) regime spectrum,
commonly known as the N2 "laser". In the present paper, this particularity, due
to gain of the transition, is analyzed from an experimental and theoretical point
of view, and for the first time has its experimental and theoretical intensities
fully compared. An experimental rotational spectrum is obtained for this
transition and a model for the ASE intensities has been carried out in order to
retrieve the experimental conditions. The theoretical calculations of the gain
have been carried out through a model proposed by other authors, as explained in
the article. For the comparison among the ASE experimental and theoretical
intensities, the fast and slow relaxation approximations proposed have been used,
being the first one that best reproduces the experimental spectrum. For the first
time, the experimental and theoretical spectra are compared directly, allowing
the precise determination of the vibrational coefficient of inversion and
temperature, showing the possible problems arising from the approximation. A good
agreement between experimental and theoretical results is observed showing the
reasonable validity of the model for the gain.
PMID- 29938524
TI - Prescribing patterns of oral antiplatelets in Wales: evolving trends from 2005 to
2016.
AB - AIM: Antiplatelets have been used for decades to prevent atherothrombotic
disease, but there is limited 'real-life' prescribing data. We hereby report the
prescribing patterns for oral antiplatelets in Wales, UK. METHODS/RESULTS:
Retrospective analysis of anonymized data in Wales from 2005 to 2016 revealed
differences in prescribing patterns of oral antiplatelets. Aspirin and
dipyridamole use declined with a corresponding increase in clopidogrel
prescription. Costs declined with a sharp decrease coinciding with clopidogrel
coming off patent. Prasugrel and ticagrelor have shown significant cost
contribution (29% of total) despite only forming 1% of total items prescribed in
2016. CONCLUSION: This first-look analysis of real-life antiplatelet data
demonstrates a decrease in the overall prescribing costs with varying patterns.
This may aid policy-makers in reviewing funding strategies.
PMID- 29938526
TI - Why are women with obesity more likely to develop breast cancer.
PMID- 29938525
TI - The role of clinical and molecular factors in low-grade gliomas: what is their
impact on survival?
AB - AIM: To evaluate relevance of clinical and molecular factors in adult low-grade
gliomas (LGG) and to correlate with survival. METHODS: We reviewed records from
adult LGG patients from 1991 to 2015 who received surgery and had sufficient
tissue to molecular biomarkers characterization. RESULTS: 213 consecutive LGG
patients were included: 17.4% were low-risk, according to Radiation Therapy
Oncology Group (RTOG) risk assessment. IDH 1/2 mutation, 1p/19q co-deletion, MGMT
methylation were found in 93, 50.8 and 65.3% of patients. Median follow-up was
98.3 months. In univariate analysis, overall survival was influenced by extent of
resection (p = 0.011), IDH mutation (p < 0.001), 1p/19q co-deletion (p = 0.015)
and MGMT methylation (p = 0.013). In multivariate analysis, RTOG clinical risk (p
= 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated
with overall survival. RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001)
and 1p/19q co-deletion (p = 0.035) correlated with overall survival. CONCLUSION:
Both clinical and molecular factors are essential to determine prognosis and
treatment strategies.
PMID- 29938527
TI - Effects of Controlling Abnormal Joint Movement on Expression of MMP13 and TIMP-1
in Osteoarthritis.
AB - Objective Abnormal joint movement is associated with osteoarthritis (OA).
Previous studies using the controlling abnormal joint movement (CAJM) model of OA
reported delayed cartilage degeneration; however, none of them focused on gait
performance and the localization of matrix metalloproteinase 13 (MMP13) and
tissue inhibitor of metalloproteinase-1 (TIMP-1) in chondrocytes. Therefore, we
aimed to investigate the effect of controlling abnormal joint movement on gait
performance and the localization of MMP13 and TIMP-1, using kinematic and
histological analyses. Design Rats were assigned to 2 groups: anterior cruciate
ligament transection (ACL-T) group and CAJM group ( n = 5/group); contralateral
hind limbs of ACL-T rats were designated as intact. After 1, 2, and 4 weeks, step
length was analyzed, and after 2, 4, and 8 weeks, Safranin O-Fast Green staining
and immunohistochemical staining for MMP13 and TIMP-1 were performed. Results
Step length did not differ significantly between the groups. However,
degeneration of articular cartilage was higher in the ACL-T group than in the
intact group ( P < 0.05). There was no significant difference in the CAJM group
at all time points. Immunohistochemical analysis of the MMP13/TIMP-1 relationship
revealed a significant increase in the expression ratio of MMP13 after 4 weeks in
the ACL-T group compared to the CAJM group ( P < 0.05). Conclusions Controlling
abnormal joint movement may reduce mechanical stress owing to kinematic elements
of small articulation including joint instability and delayed cartilage
degeneration, despite the lack of kinematic change in step length.
PMID- 29938528
TI - Interventionist Acquisition of Incidental Teaching Using Pyramidal Training via
Telehealth.
AB - We investigated the effects of a telehealth pyramidal training package on
participants' implementation of incidental teaching. A total of eight adults
worked with eight children with autism. Coaches were first taught to implement
incidental teaching and then taught subsequent interventionists. The training
package consisted of an online module and delayed video-based feedback provided
via videoconferencing. Following the telehealth training program, coaches and
interventionists reached the preset performance criteria and implemented
incidental teaching with high fidelity. All of the child participants increased
mands above baseline levels. Results suggest that interventionists can be trained
via telehealth in behavior analytic interventions.
PMID- 29938529
TI - A study of measuring participation according to the International Classification
of Functioning, Disability and Health with the Revised Role Checklist.
AB - OBJECTIVE:: To empirically test the hypothesis that the 10 roles on the Revised
Role Checklist are represented in the International Classification of
Functioning, Disability and Health participation areas. DESIGN:: Cross-sectional
survey. SUBJECTS:: Investigators from Japan, Norway, Sweden, Switzerland, the
United Kingdom and the United States recruited a total of 295 adults from the
general population. There were 103 (34.9%) male and 191 (64.7%) female
participants with one participant not indicating gender. The age distribution of
participants was from <25 ( n = 68) to 75+ with a mode of 25-34 years. MAIN
MEASURE:: The Revised Role Checklist Part 1 was used to assess perceived
incumbency in 10 roles. In addition, subjects were asked to provide role
examples. RESULTS:: Of the 7087 examples provided by participants, 6578 (92.8%)
fit the original hypothesis that the roles in the Revised Role Checklist were
covered in participation areas. Fit was determined when the role example was
either named in the associated International Classification of Functioning,
Disability and Health participation area or when the criteria of: "does this
example conceivably fit in the respective area as 'a person's involvement in life
situations' fit relative to each role." Slight modification of the scope of three
roles of the original hypothesis resulted in a 97.6% match. CONCLUSION:: The
roles in the Revised Role Checklist are well represented in the International
Classification of Functioning, Disability and Health categories of participation.
PMID- 29938530
TI - Anti-Inflammatory Effect of Carprofen Is Enhanced by Avocado/Soybean
Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination in Chondrocyte
Microcarrier Spinner Culture.
AB - Objective Osteoarthritis is a painful, chronic joint disease affecting man and
animals with no known curative therapies. Palliative nonsteroidal anti
inflammatory drugs (NSAIDs) are commonly used but they cause adverse side effects
prompting the search for safer alternatives. To address this need, we evaluated
the anti-inflammatory activity of avocado/soybean unsaponifiables (ASU),
glucosamine (GLU), and chondroitin sulfate (CS) with or without the NSAID
carprofen. Design Canine chondrocytes were propagated in microcarrier spinner
culture and incubated with (1) control medium, (2) ASU (8.3 ug/mL) + GLU (11
ug/mL) + CS (20 ug/mL) combination for 24 hours; and/or carprofen (40 ng/mL).
Cultures were next incubated with control medium alone or IL-1beta (10 ng/mL) for
another 24 hours. Production of PGE2, IL-6, IL-8, and MCP-1 (also known as CCL-2)
were measured by ELISA. Results Chondrocytes proliferated in microcarrier spinner
culture and produced type II collagen and aggrecan. Stimulation with IL-1beta
induced significant increases in PGE2, IL-6, IL-8, and MCP-1 production. The
increases in production were suppressed by carprofen as well as [ASU+GLU+CS]. The
combination of carprofen and [ASU+GLU+CS] reduced PGE2 production significantly
more than either preparation alone. The inhibitory effect of carprofen on IL-6,
IL-8, and MCP-1 production was significantly less than that of [ASU+GLU+CS],
whereas the combination did not reduce the production of these molecules
significantly more than [ASU+GLU+CS] alone. Conclusions The potentiating effect
of [ASU+GLU+CS] on low-dose carprofen was identified in chondrocyte microcarrier
spinner cultures. Our results suggest that the combination of low-dose NSAIDs
like carprofen with [ASU+GLU+CS] could offer a safe, effective management for
joint pain.
PMID- 29938531
TI - Culture and psychism: the ethnopsychoanalysis of Georges Devereux.
AB - This paper introduces the significant theoretical contribution of Georges
Devereux (1908-85) on the relationship between culture and psychism, which he
developed in his work at the interface of anthropology, psychoanalysis and
quantum epistemology during the mid-twentieth century. Devereux was one of the
key early contributors to the field of transcultural psychiatry; he was in touch
with its most important exponents, although he remained critical of many of the
popular trends developed in this field of research in the USA, where Devereux
conducted most of his research between 1932 and 1963. As a part of his critique,
he founded a new epistemology: ethnopsychoanalysis, which was largely based on
the concept of complementarity and countertransference.
PMID- 29938532
TI - Relationship between CYP1B1 polymorphisms (c.142C > G, c.355G > T, c.1294C > G)
and lung cancer risk in Polish smokers.
AB - AIM: To determine whether three of CYP1B1 single nucleotide polymorphisms, c.142C
> G, c.355G > T and c.1294C > G are associated with a lung cancer risk. PATIENTS
& METHODS: A total of 112 lung cancer patients and 100 controls were genotyped
using the RFLP-PCR. RESULTS: In the c.142C > G polymorphisms, G allele was more
frequent in lung cancer patients than in controls (p < 0.001), while in the
c.1294C > G polymorphisms, C allele was more frequent in lung cancer patients,
than in controls (p = 0.012). In the c.355G > T polymorphism, the distribution of
alleles in both analyzed groups was similar. The GTC haplotype turned out to be
correlated with the increased lung cancer risk, compared with the most common CGG
haplotype (OR: 2.38; p = 0.001). CONCLUSION: CYP1B1 gene polymorphisms appear to
influence lung cancer susceptibility.
PMID- 29938533
TI - Effect of Ranolazine on Ischemic Myocardium IN Patients With Acute Cardiac
Ischemia (RIMINI-Trial): A Randomized Controlled Pilot Trial.
AB - BACKGROUND: Coronary artery disease is the most prevalent manifestation among
cardiovascular diseases. Despite modern treatment, risk of ischemic complications
in patients with acute coronary syndrome (ACS) remains important. The late Na+
current blocker ranolazine has shown to reduce the risk of recurrent ischemia and
worsening of angina in patients with non-ST-segment elevation ACS by possibly
improving myocardial perfusion, but up to now no trial has addressed whether this
enhanced perfusion also leads to a decrease in ischemic myocardium of patients
with ACS. We designed a pilot trial (Reduction of Ischemic Myocardium with
Ranolazine-Treatment IN patients with acute myocardial Infarction,
ClinicalTrials.gov Identifier: NCT01797484) for feasibility and proof of concept
that a 6-week ranolazine add-on therapy would reduce the area of ischemic
myocardium in patients with ACS. METHODS AND RESULTS: The trial was designed in a
2-armed, controlled and randomized way. Twenty participants with unstable angina,
proof of acute cardiac ischemia, and myocardial dyskinesia by speckle-tracking
echocardiography were included. Ten participants received the study drug
ranolazine additionally to standard treatment. The control group received
standard treatment without additional study medication. Speckle-tracking
echocardiography was performed before coronary intervention, before the first
dose of ranolazine, and after 6 weeks of ranolazine treatment. Ranolazine was
administered safely during acute myocardial infarction. Speckle-tracking
echocardiography proved to be suitable for evaluation of myocardial dyskinesia.
Patients receiving ranolazine showed a trend to higher normal fraction of the
cumulative global strain than patients in the standard treatment group (15% vs
11%). No major complications relating study medication were observed. CONCLUSION:
In conclusion, in this preliminary hypothesis-driven study, 6-week ranolazine
therapy was shown to decrease the area of dyskinetic myocardium in patients with
ACS by trend. Global strain rate measurement using speckle-tracking
echocardiography can be applied measuring those effects and is, compared to other
techniques, safe and harmless. Our data provide a sound basis for a follow-up
trial.
PMID- 29938534
TI - Development and Evaluation of a Physician-Targeted Video to Promote HIV
Screening.
AB - INTRODUCTION: Despite national recommendations, routine opt-out HIV testing has
not been widely adopted by physicians. Guided by previous research on physician
barriers to HIV testing, we developed a physician-targeted video to promote
routine opt-out HIV screening. The objective of this study was to evaluate this
video intervention. METHODS: From June to July 2016, physicians in two primary
care clinics completed an online survey prior to and after watching the video.
Survey items assessed acceptability of the video and HIV testing knowledge,
attitudes, and intention to screen. Descriptive statistics were generated to
analyze data. RESULTS: Of the 53 participants, 90% liked or strongly liked the
video. Pre- to postvideo, significant improvements were seen in the knowledge of
national HIV screening recommendations (45.3% to 67.9%; p = .010) and of the
proportion of unaware Houstonians living with HIV (22.6% to 75.5%; p < .001).
Participant beliefs about the likelihood of patients accepting HIV testing
increased from 47.2% to 84.9% pre- to postvideo ( p < .001). Intention to screen
did not change; participants had high intentions pre- and postvideo. CONCLUSIONS:
Our study found that a video is an acceptable HIV testing promotion medium for
physicians. Our video improved physician HIV testing knowledge and attitudes,
overcoming key barriers to HIV testing.
PMID- 29938535
TI - A Multifaceted Approach to Public Health Career and Professional Development
Training.
AB - The purpose of this article is to describe how a multifaceted approach to career
and professional development training, focused on core competencies, student
driven programming, inter and multidisciplinary collaboration, and cultivating a
community of insight and support, is being implemented by a university Public
Health Career Services office with limited staff and resources and to share these
practices for other public health programs to scale this approach to their own
students' needs. The design of the career and professional development training
program comprised five main approaches: (1) one-on-one career counseling, (2)
peer-to-peer learning workshops, (3) community partnerships and experiential
opportunities, (4) student-driven programming, and (5) accessible training and
digital resources. All programs were tracked to gauge participation and to assess
effectiveness. Noteworthy findings from program evaluations include (1) a large
increase in student confidence levels in professionalism topics, from all of the
school's departments; (2) benefits of student-driven programming and peer-to-peer
learning, and (3) importance of employer and alumni engagement. Rather than use
an optional participation model, it is recommended that a cohort model or
mandatory participation be implemented as the opportunity to build on curriculum
is vital.
PMID- 29938536
TI - Developing a Theoretical Framework for a Complex Maternal-Child Health
Intervention: Health Beginning Initiative.
AB - A theoretical framework serves as a roadmap for the implementation and
application of a complex, health promotion intervention; is used to test
hypotheses; and guides analysis and evaluation of the intervention. The purpose
of this article is to demonstrate how a theoretical framework was developed and
used to guide the implementation of Healthy Beginning Initiative (HBI) to promote
uptake of HIV services in a low-income country. We used the guide for developing
a theoretical framework published in Health Promotion Practice. Developing the
theoretical framework included seven steps: (1) identifying the essential
elements of the intervention; (2) identifying the variables and the context; (3)
listing the postulated mechanisms, mediating variables, and postulated outcomes;
(4) identifying existing theoretical models supporting the theoretical framework
underdevelopment; (5) scripting the theoretical framework into either a figure or
sets of statements; (6) conducting content and face validation of the theoretical
framework; and (7) revising the theoretical framework. The theoretical framework
was developed and used to evaluate HBI's impact on HIV testing, linkage to care
and retention in care for pregnant women, their male partners, and newborns. The
theoretical framework will also be adapted for other screenings and other
settings while remaining true to the essential elements of HBI.
PMID- 29938537
TI - Exoplanet Biosignatures: Observational Prospects.
AB - Exoplanet hunting efforts have revealed the prevalence of exotic worlds with
diverse properties, including Earth-sized bodies, which has fueled our endeavor
to search for life beyond the Solar System. Accumulating experiences in
astrophysical, chemical, and climatological characterization of uninhabitable
planets are paving the way to characterization of potentially habitable planets.
In this paper, we review our possibilities and limitations in characterizing
temperate terrestrial planets with future observational capabilities through the
2030s and beyond, as a basis of a broad range of discussions on how to advance
"astrobiology" with exoplanets. We discuss the observability of not only the
proposed biosignature candidates themselves but also of more general planetary
properties that provide circumstantial evidence, since the evaluation of any
biosignature candidate relies on its context. Characterization of temperate Earth
sized planets in the coming years will focus on those around nearby late-type
stars. The James Webb Space Telescope (JWST) and later 30-meter-class ground
based telescopes will empower their chemical investigations. Spectroscopic
studies of potentially habitable planets around solar-type stars will likely
require a designated spacecraft mission for direct imaging, leveraging
technologies that are already being developed and tested as part of the Wide
Field InfraRed Survey Telescope (WFIRST) mission. Successful initial
characterization of a few nearby targets will be an important touchstone toward a
more detailed scrutiny and a larger survey that are envisioned beyond 2030. The
broad outlook this paper presents may help develop new observational techniques
to detect relevant features as well as frameworks to diagnose planets based on
the observables. Key Words: Exoplanets-Biosignatures-Characterization-Planetary
atmospheres-Planetary surfaces. Astrobiology 18, 739-778.
PMID- 29938539
TI - Prevalence and Risk Factors for Fecal Incontinence in Home Hospice.
AB - INTRODUCTION: We sought to determine the prevalence and risk factors associated
with fecal incontinence (FI) in the home hospice setting. METHODS: We conducted a
retrospective cohort study of patients served by a hospice agency. Data on
patient characteristics were extracted from hospice medical records. The primary
outcome, FI, was assessed routinely during clinical visits to the patient's home.
Descriptive statistics were used to summarize patient characteristics. A Cox
proportional hazards regression model was estimated for FI to examine
associations with sociodemographic and clinical characteristics of patients.
RESULTS: A total of 15 432 patients were eligible. Patients were female (59.0%)
and 75 years or older (23.5% were 75-84; 39.9% were 85+). Most patients with FI
indicated incontinence at the time of hospice admission (64.5%; n = 4314), with
the average onset period being approximately 18 days from admission (mean = 17.9,
standard deviation = 50.6). Increasing age represented a risk factor for FI
(hazard ratio [HR] = 1.01 [confidence interval, CI = 1.01-1.01]). The absence of
a health-care proxy was associated with an increased risk of FI (HR = 1.11 [CI =
1.04-1.19]). Greater risk of FI was observed among patients with dementia (HR =
1.34 [1.24-1.46]) and stroke (HR = 1.42 [1.26-1.60]) compared to patients with
cancer. Patients referred to hospice from settings other than the hospital also
had a greater risk of FI compared to those referred from the hospital (HR = 1.17
[1.11-1.23]). CONCLUSION: Fecal incontinence is a highly prevalent condition
among home hospice patients and most patients indicated FI upon admission (median
time to detection = 18 days). Further studies are needed to identify modifiable
risk factors for FI detection and its symptom management in this patient
population.
PMID- 29938540
TI - Prevalence of carbapenemase-producing organisms at the Kidney Center of
Rawalpindi (Pakistan) and evaluation of an advanced molecular microarray-based
carbapenemase assay.
AB - AIM: A DNA microarray-based assay for the detection of antimicrobial resistance
(AMR) genes was used to study carbapenemase-producing organisms at the Kidney
Center of Rawalpindi, Pakistan. METHODS: The evaluation of this assay was
performed using 97 reference strains with confirmed AMR genes. Testing of 7857
clinical samples identified 425 Gram-negative bacteria out of which 82 appeared
carbapenem resistant. These isolates were analyzed using VITEK-2 for phenotyping
and the described AMR assay for genotyping. RESULTS: The most prevalent
carbapenemase gene was blaNDM and in 12 isolates we detected two carbapenemase
genes (e.g., blaNDM/blaOXA-48). CONCLUSION: Our prevalence data from Pakistan
show that - as in other parts of the world - carbapenemase-producing organisms
with different underlying resistance mechanisms are emerging, and this warrants
intensified and constant surveillance.
PMID- 29938541
TI - Characterizing Employees' Preferences for Incentives for Healthy Behaviors:
Examples to Improve Interest in Wellness Programs.
AB - BACKGROUND: Many employers now incentivize employees to engage in wellness
programs, yet few studies have examined differences in preferences for
incentivizing participation in healthy behaviors and wellness programs. METHOD:
We surveyed 2,436 employees of a large university about their preferences for
incentivizing participation in different types of healthy behaviors and then used
multivariable logistic regression to estimate associations between employees'
socioeconomic and demographic characteristics and their preferences for
incentives for engaging in healthy behaviors. RESULTS: Compared with nonunion
members, union members had higher odds of wanting an incentive for eating
healthily (adjusted odds ratio [AOR] = 1.60, 95% [CI; 1.21, 2.12]), managing
weight (AOR = 1.53, 95% CI [1.14, 2.06]), avoiding drinking too much alcohol (AOR
= 1.41, 95% CI [1.11, 1.78]), quitting tobacco (AOR = 1.37, 95% CI [1.06, 1.77]),
managing stress (AOR = 1.37, 95% CI [1.08, 1.75]), and managing back pain (AOR =
1.64, 95% CI [1.28, 2.10]). Compared with staff, faculty employees reported
higher odds for wanting an incentive for reducing alcohol intake (AOR = 1.34, 95%
CI [1.00, 1.78]) and quitting tobacco (AOR = 1.43, 95% CI [1.04, 1.96]). Women
had lower odds than men (AOR = 0.80, 95% CI [0.64, 0.99]) of wanting an incentive
for managing back pain. CONCLUSIONS: Preferences for incentives to engage in
different types of healthy behaviors differed by employees' socioeconomic and
demographic characteristics. Organizations may consider using survey data on
employee preferences for incentives to more effectively engage higher risk
populations in wellness programs.
PMID- 29938538
TI - Exoplanet Biosignatures: Future Directions.
AB - We introduce a Bayesian method for guiding future directions for detection of
life on exoplanets. We describe empirical and theoretical work necessary to place
constraints on the relevant likelihoods, including those emerging from better
understanding stellar environment, planetary climate and geophysics, geochemical
cycling, the universalities of physics and chemistry, the contingencies of
evolutionary history, the properties of life as an emergent complex system, and
the mechanisms driving the emergence of life. We provide examples for how the
Bayesian formalism could guide future search strategies, including determining
observations to prioritize or deciding between targeted searches or larger lower
resolution surveys to generate ensemble statistics and address how a Bayesian
methodology could constrain the prior probability of life with or without a
positive detection. Key Words: Exoplanets-Biosignatures-Life detection-Bayesian
analysis. Astrobiology 18, 779-824.
PMID- 29938542
TI - Setting up multivariate specifications on critical raw material attributes to
ensure consistent drug dissolution from high drug-load sustained-release matrix
tablet.
AB - The purpose of this study was to describe the raw material variability that
influenced the in-vitro dissolution behavior of high drug-load sustained-release
matrix tablet and to ensure the consistent quality of the final product. The
Panax notoginseng saponins (PNS) - hydroxypropyl methylcellulose - anhydrous
lactose - magnesium stearate (57:20:23:0.5%, w/w) was used as the model
formulation. PNS extract powders with lot-to-lot and source-to-source differences
were collected to cover the common cause variations and their physicochemical
properties were characterized by the chromatographic fingerprints and the SeDeM
expert system. It was found that the release behavior of active pharmaceutical
ingredients (APIs) in PNS from different batches exhibited considerable
variations. Latent variable modeling results demonstrated that the physical
properties of raw materials played major roles in predicting the drug
dissolution. PNS extracts with high specific surface area, the width of particle
size distribution and hygroscopicity or low moisture content led to an increase
in drug release. In order to perform efficient pass/fail judgments for incoming
new materials, multivariate specifications of critical material attributes (CMAs)
were established and the multivariate design space in line with the quality by
design (QbD) principles was explored to achieve the release target.
PMID- 29938543
TI - Biological therapies for eosinophilic asthma.
AB - INTRODUCTION: Severe uncontrolled asthma is by definition refractory to
traditional therapies or can be controlled only with therapies that have
intolerable side effects. Monoclonal antibodies that target interleukin (IL)-5/IL
5Ralpha, IgE, and IL-4Ralpha have shown favorable results in clinical trials,
including reductions in asthma exacerbations and other important clinical
outcomes. These biological agents offer treatment alternatives to patients with
uncontrolled severe eosinophilic asthma. Areas covered: This article reviews how
the shifting emphasis toward identifying distinct asthma phenotypes has led to
the approval of biological therapies that preferentially benefit patients with
severe eosinophilic asthma. The clinical trials that led to the approval of these
biologic treatments are discussed in detail. Expert opinion: Biologic therapies
targeting the IL-5, IgE, IL-4/IL-13 signaling pathways have been successful in
clinical trials in subjects with severe eosinophilic asthma. Some of these agents
have also been successful regardless of peripheral blood eosinophil counts. These
treatments have shown a relatively favorable safety profile in clinical trials,
although long-term safety data for some of these agents are limited. Due to the
high costs associated with these medications, they should be reserved for select
patients where they yield a therapeutic and pharmacoeconomic advantage.
PMID- 29938544
TI - Topical delivery of tetrahydrocurcumin lipid nanoparticles effectively inhibits
skin inflammation: in vitro and in vivo study.
AB - Tetrahydrocurcumin (THC) also referred to as 'white curcumin', is a stable
colorless hydrogenated product of curcumin with superior antioxidant and anti
inflammatory properties. The present study is an attempt to elevate the topical
bioavailability of THC, post-incorporation into a nano-carrier system with its
final dosage as a hydrogel. Lipid nanoparticles of THC (THC-SLNs) prepared by
microemulsification technique were ellipsoidal in shape (revealed in transmission
electron microscopy) with a mean particle size of 96.6 nm and zeta potential of
22 mV. Total drug content and entrapment efficiency of THC-SLNs was 94.51% +/-
2.15% and 69.56% +/- 1.35%, respectively. Differential scanning calorimetry and X
ray diffraction studies confirmed the formation of THC-SLNs. In vitro drug
release studies showed the drug release from THC-SLNs gel to follow Higuchi's
equation revealing a Fickian diffusion. Ex vivo permeation studies indicated a 17
times (approximately) higher skin permeation of THC-SLNs gel as compared with the
free THC gel. Skin irritation, occlusion, and stability studies indicated the
formulation to be nonirritating, and stable with a desired occlusivity.
Pharmacodynamic evaluation in an excision wound mice model clearly revealed the
enhanced anti-inflammatory activity of THC-SLNs gel and was further confirmed
using biochemical and histopathological studies. It is noteworthy to report here
that THC-SLNs gel showed significantly better (p <= 0.001) activity than free THC
in gel. As inflammation is innate to all the skin disorders, the developed
product opens up new therapeutic avenues for several skin diseases. To the best
of our knowledge, this is the first paper elaborating the therapeutic usefulness
of white curcumin-loaded lipidic nanoparticles for skin inflammation.
PMID- 29938545
TI - Janus kinase inhibitors for the treatment of inflammatory bowel diseases:
developments from phase I and phase II clinical trials.
AB - INTRODUCTION: A new pharmacological class, Janus kinases (JAK) inhibitors, has
been shown to be effective and safe for the treatment of inflammatory bowel
diseases (IBDs). The aim of this review is to provide an overview of the JAK
inhibitors currently under investigation in phase I and II clinical trials for
patients with Crohn's disease and ulcerative colitis and the possible future
perspectives for the treatment of IBD patients with this class of drugs. Areas
covered: This review describes the JAK-STAT pathway and analyzes the efficacy and
safety of new small molecules such as filgotinib, upadacitinib, TD-1473,
peficitinib, and Pf-06651600/Pf-06700841, showing data from phase I and II
trials. Expert Opinion: JAK inhibitors, if approved by the regulatory
authorities, could represent a novel and intriguing drug class. In the next
years, the approach to patients with IBD will become increasingly personalized.
PMID- 29938547
TI - How to identify and prioritize procedures suitable for simulation-based training:
Experiences from general needs assessments using a modified Delphi method and a
needs assessment formula.
AB - Simulation-based training (SBT) is a revolutionary addition to the education of
residents in different specialties. However, the selection of training programs
is often reliant on commercially available equipment or on experiential notions,
local interests or coincidence. The first step to developing training programs
should be problem identification and general needs assessment to ensure that
these are aligned with current trainee needs. We describe a stepwise approach to
performing a needs assessment following the Delphi process and using a needs
assessment formula (NAF) to prioritize technical procedures for simulation
training. This technique relies on a panel of experts to gather information and
achieve a convergence of opinion. We used three rounds of survey iterations.
Round 1: A brainstorming phase to gather all procedures that a newly qualified
resident should be able to perform. Round 2: Rating and preliminary
prioritization with a NAF including frequency of the procedure, number of
doctors, impact, and feasibility. Round 3: Elimination and final prioritization
of procedures. The needs assessment identifies and prioritizes procedures for
simulation training. It can guide medical educators in the planning of SBT
programs to address current trainee needs with the aim of improving the education
and training of future doctors.
PMID- 29938546
TI - The dark side of ibuprofen in the treatment of patent ductus arteriosus: could
paracetamol be the solution?
AB - INTRODUCTION: Patent ductus arteriosus (PDA) persistence is associated, in
prematures, to several complications. The optimal PDA management is still under
debate, especially regarding the best therapeutic approach and the time to treat.
The available drugs are not exempt from contraindications and side effects;
ibuprofen itself, although representing the first-choice therapy, can show
nephrotoxicity and other complications. Paracetamol seems a valid alternative to
classic nonsteroidal anti-inflammatory Drugs, with a lower toxicity. Areas
covered: Through an analysis of the published literature on ibuprofen and
paracetamol effects in preterm neonates, this review compares the available
treatments for PDA, analyzing the mechanisms underlining ibuprofen-associated
nephrotoxicity and the eventual paracetamol-induced hepatic damage, also
providing an update of what has been yet demonstrated and a clear description of
the still open issues. Expert Opinion: Paracetamol is an acceptable alternative
in case of contraindication to ibuprofen; its toxicity, in this setting, is very
low. Lower doses may be effective, with even fewer risks. In the future,
paracetamol could represent an efficacious first-line therapy, although its
safety, optimal dosage, and global impact have to be fully clarified through long
term trials, also in the perspective of an individualized and person-based
therapy taking into account the extraordinary individual variability.
PMID- 29938548
TI - CD10, TDAG51, CK20, AR, INSM1, and Nestin Expression in the Differential
Diagnosis of Trichoblastoma and Basal Cell Carcinoma.
AB - BACKGROUND: Trichoblastoma (TB) and basal cell carcinoma (BCC) are 2 different
neoplasms composed of basaloid cells and have overlapping histopathological
features. We compared the immunoexpression of CD10, T-cell death-associated gene
51 (TDAG51), cytokeratin 20 (CK20), androgen receptor (AR), insulinoma-associated
protein 1 (INSM1), and nestin for the differential diagnosis of these tumors.
MATERIALS AND METHODS: We assessed a total of 27 BCC and 27 TB cases, including 4
TB lesions in nevus sebaceous and 3 malignant TB lesions for CD10, TDAG51, CK20,
AR, INSM1, and nestin expression. RESULTS: Staining for CK20, TDAG51, INSM1, and
stromal CD10 was significantly more common in TB cases than in BCC cases ( P <
.001). Epithelial CD10 and AR staining was significantly more common in BCC cases
than in TB cases ( P < .001). The difference between the groups for nestin
staining was not significant ( P > .05). Stromal CD10 staining was the most
sensitive marker (96.3%) and INSM1 the least sensitive (55.6%) marker for TB.
TDAG51 showed 100% specificity for TB. A larger number of CK20 positive cells was
found in the cases associated with nevus sebaceous than in the other TBs.
CONCLUSION: All the selected markers except nestin were useful for the
differential diagnosis between TB and BCC. CD10 and TDAG51 were more useful than
the other markers. The use of CK20 could be preferred in nevus sebaceous lesions.
INSM1 was less effective in highlighting Merkel cells within the lesion than
CK20.
PMID- 29938549
TI - Differential Effects of Simulated Cortical Network Lesions on Synchrony and EEG
Complexity.
AB - Brain function has been proposed to arise as a result of the coordinated activity
between distributed brain areas. An important issue in the study of brain
activity is the characterization of the synchrony among these areas and the
resulting complexity of the system. However, the variety of ways to define and,
hence, measure brain synchrony and complexity has sometimes led to inconsistent
results. Here, we study the relationship between synchrony and commonly used
complexity estimators of electroencephalogram (EEG) activity and we explore how
simulated lesions in anatomically based cortical networks would affect key
functional measures of activity. We explored this question using different types
of neural network lesions while the brain dynamics was modeled with a time
delayed set of 66 Kuramoto oscillators. Each oscillator modeled a region of the
cortex (node), and the connectivity and spatial location between different areas
informed the creation of a network structure (edges). Each type of lesion
consisted on successive lesions of nodes or edges during the simulation of the
neural dynamics. For each type of lesion, we measured the synchrony among
oscillators and three complexity estimators (Higuchi's Fractal Dimension, Sample
Entropy and Lempel-Ziv Complexity) of the simulated EEGs. We found a general
negative correlation between EEG complexity metrics and synchrony but Sample
Entropy and Lempel-Ziv showed a positive correlation with synchrony when the
edges of the network were deleted. This suggests an intricate relationship
between synchrony of the system and its estimated complexity. Hence, complexity
seems to depend on the multiple states of interaction between the oscillators of
the system. Our results can contribute to the interpretation of the functional
meaning of EEG complexity.
PMID- 29938550
TI - Barriers and Facilitators to Effective Mental Health Care in Correctional
Settings.
AB - It is estimated that one third to one half of the 2.3 million individuals inside
U.S. jails and prisons have a mental illness in contrast to 18.3% of the general
population. The implications of this on training mental health professionals to
provide efficacious treatment inside correctional facilities, as well as planning
for the rehabilitation and reintegration of incarcerated individuals, are
significant and numerous. This article will present a brief history and overview
of mental health services in the U.S. correctional system, as well as a
discussion of the barriers to and potential facilitators of providing effective
care in the future.
PMID- 29938551
TI - Risk factors for abnormally invasive placenta: a systematic review and meta
analysis.
AB - : Purpose of the article. To explore the strength of association between
different maternal and pregnancy characteristics and the occurrence of abnormally
invasive placenta (AIP). MATERIALS AND METHODS: Pubmed, Embase, CINAHL databases
were searched. The risk factors for AIP explored were: obesity, age >35 years,
smoking before or during pregnancy, placenta previa, prior cesarean section (CS),
placenta previa and prior CS, prior uterine surgery, abortion and uterine
curettage, in vitro fertilization (IVF) pregnancy and interval between a previous
CS, and a subsequent pregnancy. Random-effect head-to-head meta-analyses were
used to analyze the data. RESULTS: Forty-six were included in the systematic
review. Maternal obesity (Odd ratio, OR: 1.4, 95% CI 1.0-1.8), advanced maternal
age (OR: 3.1, 95% CI 1.4-7.0) and parity (OR: 2.5, 95% CI 1.7-3.6), but not
smoking were associated with a higher risk of AIP. The presence of placenta
previa in women with at least a prior CS was associated with a higher risk of AIP
compared to controls, with an OR of 12.0, 95% CI 1.6-88.0. Furthermore, the risk
of AIP increased with the number of prior CS (OR of 2.6, 95% CI 1.6-4.4 and 5.4,
95% CI 1.7-17.4 for two and three prior CS respectively). Finally, IVF
pregnancies were associated with a high risk of AIP, with an OR of 2.8 (95% CI
1.2-6.8). CONCLUSION: A prior CS and placenta previa are among the strongest risk
factors for the occurrence of AIP.
PMID- 29938552
TI - Isoflurane decreases interleukin-2 production by increasing c-Cbl and Cbl-b
expression in rat peripheral blood mononuclear cells.
AB - Objective To evaluate how isoflurane affects T-cell function by assaying
interleukin (IL)-2 production and the expression of two Casitas B-lineage
lymphoma (Cbl) family proto-oncogenes (c-Cbl and Cbl-b) in rat peripheral blood
mononuclear cells (PBMCs). Methods Adult male Sprague-Dawley rats were randomly
allocated to those that underwent blood collection after brief isoflurane
anesthesia (control group), immediately after 4 hours of isoflurane general
anesthesia (4I group), and 1 day after 4 hours of isoflurane general anesthesia
(1D 4I group). IL-1, IL-2, and IL-6 mRNA levels and c-Cbl and Cbl-b levels in
PBMCs were determined by polymerase chain reaction. Ubiquitination of protein
kinase Ctheta (PKCtheta) and phospholipase C-gamma1 (PLC-gamma1) in PBMCs was
assessed by immunoprecipitation. Results The IL-2 mRNA level in rat PBMCs was
significantly lower in the 4I and 1D 4I groups than in the control group. c-Cbl,
Cbl-b, and ubiquitin expression was significantly increased and zeta-chain
associated protein kinase 70, PLC-gamma1, and PKCtheta protein levels were
significantly decreased in the 4I group. Ubiquitination of PLC-gamma1 and
PKCtheta was significantly increased in the 4I group. Conclusion Isoflurane
influences ubiquitin, c-Cbl, and Cbl-b expression in rat PBMCs, indicating
suppression of receptor tyrosine kinase signaling pathways. These results suggest
that isoflurane suppresses T-cell function.
PMID- 29938553
TI - Plantar Reconstruction Using a Dermal Substitute: Description of 2 Cases.
AB - Acral lentiginous melanoma is the most common subtype among melanomas on the
foot. Reconstruction of a wide surgical defect once it is excised may result in a
challenge that requires replacing the lost tissue with another tissue having
similarly unique physical characteristics. Although reconstructive options such
as skin grafts and either local or distant flaps offer adequate coverage, they
often are subject of contraction, muscle atrophy, and contour abnormalities.
Dermal substitutes provide support and structure and recreates the dermal layer
to ensure a durable reconstruction. We report 2 cases of plantar melanoma in
which adequate reconstruction was achieved using a dermal substitute.
PMID- 29938554
TI - Altering the boundaries of everyday life in a nursing home context.
AB - BACKGROUND: Despite global and local policy frameworks that explicitly aim to
privilege participation and active engagement of older adults living in nursing
homes, this group often has limited possibilities to engage in occupations and to
have influence in their everyday lives. AIM: To explore how older adults'
engagement and influence in an occupation can emerge in everyday life in a
nursing home setting. MATERIAL AND METHODS: A participatory qualitative approach
was applied. Older adults living in a nursing home participated in a Book Club
that was created collaboratively between researchers, residents, and the nursing
home community. FINDINGS: The analysis identified qualities of altering the
boundaries of everyday life and addressing the uncertain conditions for influence
and engagement as processes actualized by the residents when engaging in the Book
Club. Further analysis identified how these processes involved ordinariness,
familiarity, fellowship, and connectedness. CONCLUSION AND SIGNIFICANCE:
Engagement and influence in occupation in a nursing home is possible when
enabling partnerships and resourcefulness among the residents. However, such
enablement is not guaranteed and needs to be actively upheld by the nursing home
community in order to build practices aligned with policy frameworks of
participation.
PMID- 29938555
TI - Specificity of process analytical tools in the monitoring of multicomponent
pharmaceutical powders.
AB - The application of Process Analytical Technologies in pharmaceutical
manufacturing has been the subject of many studies. Active pharmaceutical
ingredient monitoring in real time throughout the manufacturing process is
commonly the target of many such implementations. The tools in place must be
sensitive to, and selective of, the parameter(s) to be monitored, i.e. in the
case of component quantification, they must respond to the component in question
and be robust against all others. In this study, four different ingredients
(riboflavin, ferrous fumarate, ginseng, and ascorbic acid) in a multi-component
blend were monitored by three different tools (near infrared spectroscopy, laser
induced fluorescence and red-green-blue camera) using a full factorial design.
The goal was to develop efficient and robust concentration-reading/prediction
models able to assess and monitor component interference. Despite relatively high
complexity of the blend studied, the three tools demonstrated reasonable
specificity for the tracked ingredients (and showed advantages when combined),
taking into account larger acceptance criteria typical of dietary products. In
certain cases, some interference might lead to biased predictions, highlighting
the importance of good calibration. The tools tested and the methodology proposed
has divulged their potential in monitoring these components, despite the
complexity of the 31-component blend.
PMID- 29938556
TI - Prenatal care and labor in patients with mesenchimal dysplasias (Marfan syndrome,
Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia).
AB - BACKGROUND: Mesenchymal dysplasias or inherited connective tissue diseases are
the group of diseases with deficiency of various components of connective tissue.
Connective tissue disorders can affect different organs: skeleton, sight organ,
skin, lungs, heart. But the most dangerous is vascular wall insufficiency leading
to high risk of hemorrhage, especially during pregnancy and delivery due to
hemodynamic and hormonal effects on the walls of the modified vessels. AIM: To
evaluate the risk of complications during the pregnancy and delivery in patients
with mesenchymal dysplasias. STUDY DESIGN: Fifty-six pregnancies in patients with
mesenchymal dysplasias, including subclinical forms of diseases: 23 with Marfan
syndrome (I group), 22 with Ehlers-Danlos syndrome (II group), and 11 with Osler
Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia) (III group) of the
age from 18 to 36. The study included retrospective analysis (for the period from
1993 to 2005) and prospective study. Results of study showed high risk of life
threatening complications during pregnancy and delivery, especially the risk of
hemorrhage and cardiovascular complications. In all the patients, we observed the
progression of bleeding or development of bleeding in new localizations
(epistaxis in 27 patients, easy brushing in 22, skin and mucosa telangiectasia in
20, gastrointestinal bleedings in 4, hemoptysis in 4, hematomas for minor traumas
in 14, conjunctivas hemorrhages in 5). CONCLUSION: The pathogenesis of bleeding
in such patients has mixed pattern: besides vascular wall pathology coagulation
deficiency plays some role. The preferred delivery method for such patients is
caesarean section. Deep vaginal ruptures and serious hemorrhage accompany vaginal
delivery.
PMID- 29938557
TI - Cognitive Group Therapy Based on Schema-Focused Approach for Reducing Depression
in Prisoners Living With HIV.
AB - Depression is one the most common mental disorders in prisons. People living with
HIV are more likely to develop psychological difficulties when compared with the
general population. This study aims to determine the efficacy of cognitive group
therapy based on schema-focused approach in reducing depression in prisoners
living with HIV. The design of this study was between-groups (or "independent
measures"). It was conducted with pretest, posttest, and waiting list control
group. The research population comprised all prisoners living with HIV in a men's
prison in Iran. Based on voluntary desire, screening, and inclusion criteria, 42
prisoners living with HIV participated in this study. They were randomly assigned
to an experimental group (21 prisoners) and waiting list control group (21
prisoners). The experimental group received 11 sessions of schema-focused
cognitive group therapy, while the waiting list control group received the
treatment after the completion of the study. The various groups were evaluated in
terms of depression. ANCOVA models were employed to test the study hypotheses.
Collated results indicated that depression was reduced among prisoners in the
experimental group. Schema therapy (ST) could reduce depression among prisoners
living with HIV/AIDS.
PMID- 29938558
TI - Characterisation of fused deposition modeling 3D printers for pharmaceutical and
medical applications.
AB - Fused deposition modeling (FDM) is a promising 3D printing technique for the
fabrication of personalized drug dosage forms and patient-specific implants.
However, there are no market products produced by FDM available at this time. One
of the reasons is the lack of a consistent and harmonized approval procedure. In
this study, three FDM printers have been characterised with respect to printing
parameters relevant for pharmaceutical and medical applications, namely the
positioning, hot-end temperature, material residence time, printing velocity and
volumetric material flow. The printers are the Ultimaker 2 (UM2), the PRotos v3
(PR3) as well as an in-house developed printer (IDP). The positioning results
showed discrepancies between the printers, which are mainly based on different
types of drive systems. Due to comparable utilised hot-ends and nozzle
geometries, the results for the temperature and residence time distribution
measurements were quite similar. The IDP has a high positioning accuracy but is
limited with respect to printing velocity, while the achievable material volume
flows were different for all printers. The presented characterisation method aims
to contribute to the development of a harmonized equipment qualification
framework for FDM printers, which could lead to an acceleration and facilitation
of an approval procedure for 3D printed products.
PMID- 29938559
TI - Decomposition of Mediterranean Dietary Pattern on Successful Aging, Among Older
Adults: A Combined Analysis of Two Epidemiological Studies.
AB - OBJECTIVE: To investigate the association of Mediterranean food group consumption
with successful aging (SA), among people more than 50 years old. METHOD: Dietary
habits, as well as several bio-clinical characteristics of the Greek participants
enrolled in the ATTICA ( n = 1,128 men and women from Athens metropolitan area)
and the MEDIS ( n = 2,221 men and women from selected Greek islands) cohort
studies were investigated in relation to SA; SA was measured using a validated 10
scale index. RESULTS: Multivariate discriminant food group analysis revealed that
legumes consumption, followed by vegetables, cereals, and poultry were associated
with higher levels of SA index (explained variability: 7.9%), mainly among
islanders, but not among mainland participants. Further analysis revealed that
alcohol consumption was positively associated with SA for mainlanders (ATTICA
study) but inversely for islanders (MEDIS study; all p's < .05). CONCLUSION: The
differential and hierarchical effect of various foods on SA and the diet
environmental interaction revealed in the present work may help health
professionals to better understand the role of diet on SA, and to prioritize the
nutritional needs of older people for better quality of life.
PMID- 29938560
TI - Experiences, Emotions, and Adjustments of HIV-Infected Men in HIV-Concordant
Marital Relationship in Cambodia.
AB - Although it has been well documented that the HIV infection experience can be
problematic for those affected, the experiences and perceptions of living with
HIV among married males in Cambodia have not yet been examined until now. This
study's purpose was to describe the revelations, emotions, reactions, and
adjustments to HIV diagnosis among infected Cambodian males in seroconcordant
heterosexual relationship. Fifteen qualitative in-depth interviews were conducted
with 15 HIV-positive males using unstructured, open-ended questions and in the
local Khmer language. Conventional content analysis method was employed for
analyzing data. After analysis, four main categories were developed: knowledge of
HIV-positive status; realization of self-deeds; discouraging news for both
partners; and comparative improvement of life. Participants reported the
appearance of physical symptoms as the only reason for pursuing HIV testing.
Feelings ranged from sadness and guilt to acceptance of HIV infection in their
lives. The participants' wives expressed anger and worry about being infected by
their husbands. However, sufficient inspiration from medical personnel and peer
groups, as well as a shared concern for their children, helped couples adjust to
their dyadic relationship. The study results highlight the link between
individual and couple experiences and emotions post-infection, with implications
for designing and implementing coping interventions for this population. The
findings of this study have public health implications in the design of couple
based intervention and counseling programs for HIV prevention and treatment with
the input of the HIV-positive individuals' voices.
PMID- 29938561
TI - Weight change over two years in people prescribed olanzapine, quetiapine and
risperidone in UK primary care: Cohort study in THIN, a UK primary care database.
AB - BACKGROUND: Follow-up studies of weight gain related to antipsychotic treatment
beyond a year are limited in number. We compared weight change in the three most
commonly prescribed antipsychotics in a representative UK General Practice
database. METHOD: We conducted a cohort study in United Kingdom primary care
records of people newly prescribed olanzapine, quetiapine or risperidone. The
primary outcome was weight in each six month period for two years after treatment
initiation. Weight changes were compared using linear regression, adjusted for
age, baseline weight and diagnosis. RESULTS: N = 6338 people received olanzapine,
12,984 quetiapine and 6556 risperidone. Baseline weight was lowest for men
treated with olanzapine (80.8 kg versus 83.5 kg quetiapine, 82.0 kg risperidone)
and women treated with olanzapine (67.7 kg versus 71.5 kg quetiapine 68.4 kg
risperidone. Weight gain occurred during treatment with all three drugs. Compared
with risperidone mean weight gain was higher with olanzapine (adjusted co
efficient +1.24 kg (95% confidence interval: 0.69-1.79 kg per six months) for men
and +0.77 kg (95% confidence interval: 0.29-1.24 kg) for women). Weight gain with
quetiapine was lower in unadjusted models compared with risperidone, but this
difference was not significant after adjustment. CONCLUSION: Olanzapine is more
commonly prescribed to people with lower weight. However, after accounting for
baseline weight, age, sex and diagnosis, olanzapine is still associated with
greater weight gain over two years than risperidone or quetiapine. Baseline
weight does not ameliorate the risks of weight gain associated with antipsychotic
medication. Weight gain should be assertively discussed and managed for people
prescribed antipsychotics, especially olanzapine.
PMID- 29938562
TI - Plasma and serum brain-derived neurotrophic factor (BDNF) levels and their
association with neurocognition in at-risk mental state, first episode psychosis
and chronic schizophrenia patients.
AB - OBJECTIVES: Brain-derived neurotrophic factor (BDNF) is involved in numerous
cognitive processes. Since cognitive deficits are a core feature of psychotic
disorders, the investigation of BDNF levels in psychosis and their correlation
with cognition has received increased attention. However, there are no studies
investigating BDNF levels in individuals with an at-risk mental state (ARMS) for
psychosis. Hence, the aims of the present study were: (1) assessing peripheral
BDNF levels across different (potential) stages of psychosis; (2) investigating
their association with cognition. METHODS: Plasma and serum BDNF levels and
neuropsychological performance were assessed in 16 ARMS, six first-episode
psychosis (FEP), and 11 chronic schizophrenia (CS) patients. Neuropsychological
assessment covered intelligence, verbal memory, working memory, attention and
executive functioning. RESULTS: Both plasma and serum BDNF levels were highest in
CS, intermediate in FEP and lowest in ARMS. Multiple regression analysis revealed
a significant positive association of plasma BDNF levels with planning ability
across all groups. CONCLUSIONS: The lower peripheral BDNF levels in ARMS compared
to FEP and CS might point towards an important drop of this neurotrophin prior to
the onset of frank psychosis. The associations of peripheral BDNF with planning
abilities match previous findings.
PMID- 29938563
TI - Psychedelics and hypnosis: Commonalities and therapeutic implications.
AB - BACKGROUND: Recent research on psychedelics and hypnosis demonstrates the value
of both methods in the treatment of a range of psychopathologies with overlapping
applications and neurophenomenological features. The potential of harnessing the
power of suggestion to influence the phenomenological response to psychedelics
toward more therapeutic action has remained unexplored in recent research and
thereby warrants empirical attention. AIMS: Here we aim to elucidate the
phenomenological and neurophysiological similarities and dissimilarities between
psychedelic states and hypnosis in order to revisit how contemporary knowledge
may inform their conjunct usage in psychotherapy. METHODS: We review recent
advances in phenomenological and neurophysiological research on psychedelics and
hypnosis, and we summarize early investigations on the coupling of psychedelics
and hypnosis in scientific and therapeutic contexts. Results/outcomes: We
highlight commonalities and differences between psychedelics and hypnosis that
point to the potential efficacy of combining the two in psychotherapy. We propose
multiple research paths for coupling these two phenomena at different stages in
the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy
in order to prepare, guide and integrate the psychedelic experience with the aim
of enhancing therapeutic outcomes. CONCLUSIONS/INTERPRETATION: Harnessing the
power of suggestion to modulate response to psychedelics could enhance their
therapeutic efficacy by helping to increase the likelihood of positive responses,
including mystical-type experiences.
PMID- 29938564
TI - The Connections Between Work, Prostate Cancer Screening, Diagnosis, and the
Decision to Undergo Radical Prostatectomy.
AB - Prostate cancer diagnosis can occur at a time when men's work and careers are
central to their masculine identity, sense of purpose, and family life. In
Canada, an aging male population, along with medical advances, has resulted in
increasing numbers of working men being diagnosed with, and treated for, prostate
cancer. Little is known about the linkages between men's work and their
experiences of prostate cancer. In this qualitative study, 24 Western Canadian
men were interviewed to distil the connections between work, prostate cancer
screening, diagnosis, and the decision to undergo radical prostatectomy. Data
were analyzed using constant comparison in the context of masculinities theory.
The findings demonstrated that work was central to men's masculine identities and
afforded financial security, social status, and a sense of personal growth.
However, work-related strain and demands were also found to affect participants'
health and distance them from their families. A diagnosis of prostate cancer
tended to diminish the importance of work, wherein participants focused on
optimizing their health and strengthening family relations. In deciding on
radical prostatectomy as a treatment to eradicate prostate cancer, few men
considered the implications for returning to work. The current study findings
indicate that clinicians and patients should explicitly explore and discuss how
surgery side effects may affect work and career plans during treatment decision
making.
PMID- 29938565
TI - Psychedelic therapy for smoking cessation: Qualitative analysis of participant
accounts.
AB - BACKGROUND: Recent pilot trials suggest feasibility and potential efficacy of
psychedelic-facilitated addiction treatment interventions. Fifteen participants
completed a psilocybin-facilitated smoking cessation pilot study between 2009 and
2015. AIMS: The aims of this study were as follows: (1) to identify perceived
mechanisms of change leading to smoking cessation in the pilot study; (2) to
identify key themes in participant experiences and long-term outcomes to better
understand the therapeutic process. METHODS: Participants were invited to a
retrospective follow-up interview an average of 30 months after initial
psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15
participants. Data were analysed using thematic analysis. RESULTS: Participants
reported gaining vivid insights into self-identity and reasons for smoking from
their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity
persisted beyond the duration of acute drug effects. Participants emphasised that
the content of psilocybin experiences overshadowed any short-term withdrawal
symptoms. Preparatory counselling, strong rapport with the study team, and a
sense of momentum once engaged in the study treatment were perceived as vital
additional factors in achieving abstinence. In addition, participants reported a
range of persisting positive changes beyond smoking cessation, including
increased aesthetic appreciation, altruism, and pro-social behaviour.
CONCLUSIONS: The findings highlight the value of qualitative research in the
psychopharmacological investigation of psychedelics. They describe perceived
connections between drug- and non-drug factors, and provide suggestions for
future research trial design and clinical applications.
PMID- 29938566
TI - Sodium Nitroprusside as a Hyperinflation Drug and Therapeutic Alternatives.
AB - Sodium nitroprusside (SNP) is a generically available and rapid-acting
intravenous (IV) vasodilator that has been used clinically for decades. Prior to
2013, the cost of SNP was relatively low, and SNP was an affordable option for
the treatment of acute hypertension. However, from 2013 to 2017, average
wholesale prices for SNP rose to as high as US$900 per vial, earning the drug its
status as a "hyperinflation drug." Hyperinflation drugs pose a significant
challenge for pharmacy departments. A multidisciplinary effort involving
stakeholders from many backgrounds, including pharmacists, physicians, and
nurses, is key to developing an effective cost containment strategy. A
therapeutic interchange, wherein a drug with similar efficacy is substituted for
another, is often an appropriate strategy to address rising drug costs.
Fortunately, alternative drugs with a solid evidence base exist for the
management of acute hypertension. The dihydropyridine calcium channel blockers,
clevidipine and nicardipine, are IV titratable antihypertensive agents with
favorable pharmacokinetic and safety profiles. Various studies indicate that
clevidipine and nicardipine are effective alternatives to SNP for indications
including hypertensive crisis and postoperative hypertension. Some hospitals have
reported significant cost savings without adverse outcomes by substituting
clevidipine or nicardipine for SNP. This article is intended to serve as a review
of the evidence for clevidipine and nicardipine as potential substitutes for SNP
and to provide strategies to successfully implement this therapeutic interchange.
PMID- 29938568
TI - Gradually Disengaging: Parent-Health care Provider Relationships After a Child's
Death in the Pediatric Intensive Care Unit.
AB - When a child dies in the intensive care unit, many bereaved parents want
relationships with their child's health care staff to continue in the form of
follow-up care. However, the nature of these relationships and how they change
across the parents' bereavement journey is currently unknown. This article
explores early and ongoing relationships between parents and health care staff
when a child dies in intensive care. Constructivist grounded theory methods were
used to recruit 26 bereaved parents from four Australian pediatric intensive care
units into the study. Data were collected via audio-recorded, semistructured
interviews and analyzed using the constant comparative methods and theoretical
memoing. Findings show that these relationships focus on Gradually disengaging,
commonly moving through three phases after the child dies: Saying goodbye, Going
home, and Seeking supports. These findings provide guidance to health care staff
on what families need as they leave the intensive care unit and move through
bereavement.
PMID- 29938567
TI - Global profiling of hnRNP A2/B1-RNA binding on chromatin highlights LncRNA
interactions.
AB - Long noncoding RNAs (lncRNAs) often carry out their functions through
associations with adaptor proteins. We recently identified heterogeneous
ribonucleoprotein (hnRNP) A2/B1 as an adaptor of the human HOTAIR lncRNA. hnRNP
A2 and B1 are splice isoforms of the same gene. The spliced version of HOTAIR
preferentially associates with the B1 isoform, which we hypothesize contributes
to RNA-RNA matching between HOTAIR and transcripts of target genes in breast
cancer. Here we used enhanced cross-linking immunoprecipitation (eCLIP) to map
the direct interactions between A2/B1 and RNA in breast cancer cells. Despite
differing by only twelve amino acids, the A2 and B1 splice isoforms associate
preferentially with distinct populations of RNA in vivo. Through cellular
fractionation experiments we characterize the pattern of RNA association in
chromatin, nucleoplasm, and cytoplasm. We find that a majority of interactions
occur on chromatin, even those that do not contribute to co-transcriptional
splicing. A2/B1 binding site locations on multiple RNAs hint at a contribution to
the regulation and function of lncRNAs. Surprisingly, the strongest A2/B1 binding
site occurs in a retained intron of HOTAIR, which interrupts an RNA-RNA
interaction hotspot. In vitro eCLIP experiments highlight additional exonic B1
binding sites in HOTAIR which also surround the RNA-RNA interaction hotspot.
Interestingly, a version of HOTAIR with the intron retained is still capable of
making RNA-RNA interactions in vitro through the hotspot region. Our data further
characterize the multiple functions of a repurposed splicing factor with isoform
biased interactions, and highlight that the majority of these functions occur on
chromatin-associated RNA.
PMID- 29938570
TI - International Journal of Hyperthermia Editors' Award Winners, 2017.
PMID- 29938569
TI - Editorial.
PMID- 29938571
TI - Reply to letter: Nephrotoxic synergism of cisplatin and mitomycin-C for
hyperthermic intraperitoneal chemotherapy and cytoreductive surgery by Kapoor R,
Robinson K and Badgwell B.
PMID- 29938572
TI - Nephrotoxic synergism of cisplatin and mitomycin-C for hyperthermic
intraperitoneal chemotherapy and cytoreductive surgery.
PMID- 29938573
TI - Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy
in a mouse model of BRCA1-deficient breast cancer.
AB - Breast cancer is a heterogeneous disease, and stratification of patients is
fundamental to the success of treatment modalities. Breast tumors deficient in
BRCA1 are mostly associated with basal-like breast cancers and targeted
therapeutics for this disease subtype are still lacking. In order to address
whether macroautophagy/autophagy inhibition will be effective in BRCA1-deficient
mammary tumors, we generated mice with conditional deletion of an essential
autophagy gene, Rb1cc1, along with Brca1 and Trp53, through utilization of the
K14-Cre transgene. We found that Rb1cc1 deletion suppressed tumorigenesis in the
BRCA1-deficient model when compared to wild type and heterozygous Rb1cc1
controls. However, in contrast to previous studies in the mouse mammary tumor
virus (MMTV)-polyoma middle T antigen (PyMT) model, tumor growth and the
distribution of histological subtypes were not affected by loss of RB1CC1.
Interestingly, loss of RB1CC1 decreased mitochondrial mass and oxidative
respiratory capacity of these tumor cells, along with a decrease in the
phosphorylation of MTOR substrates and transcript levels of genes involved in
mitochondrial biogenesis. Importantly, we observed an increased sensitivity to
mitochondrial disrupting agents upon loss of RB1CC1. Consequently, our data
showed that combination of an autophagy inhibitor, spautin-1, along with a
mitochondrial complex I inhibitor, metformin, was more effective in limiting
oxidative respiratory capacity, colony-forming ability and tumor growth.
Altogether, our results indicate that inhibition of autophagy can increase the
benefits of metformin treatment in BRCA1-deficient breast cancers.
PMID- 29938574
TI - Moral distress and burnout in Iranian nurses: The mediating effect of workplace
bullying.
AB - BACKGROUND: Moral distress and workplace bullying are important issues in the
nursing workplace that appear to affect nurse's burnout. AIM: To investigate the
relationship between moral distress and burnout in Iranian nurses, as mediated by
their perceptions of workplace bullying. Ethical considerations: The research was
approved by the committee of ethics in research of the Urmia University of
Medical Sciences. METHOD: This is a correlation study using a cross-sectional
design with anonymous questionnaires as study instruments (i.e. Moral Distress
Scale-Revised, Maslach Burnout Inventory and The Negative Acts Questionnaire
Revised). Data were collected from 278 nurses from five teaching hospitals in
Urmia, the capital of Western Azerbaijan, northwest of Iran. Structural equation
modeling and bootstrapping procedures were employed to recognize the mediating
role of their perceptions of workplace bullying. RESULTS: The mean score of moral
distress, burnout, and the Negative Acts Questionnaire-Revised Scale among the
participants were 91.02 +/- 35.26, 79.9 +/- 18.27, and 45.4 +/- 15.39,
respectively. The results confirmed our hypothesized model. All the latent
variables of study were significantly correlated in the predicted directions. The
moral distress and bullying were significant predictors of burnout. Perception of
bullying partially mediated the relationship between moral distress and burnout.
The mediating role of the bullying suggests that moral distress increases
burnout, directly and indirectly. CONCLUSION: Nursing administrators should be
conscious of the role of moral distress and bullying in the nursing workplace in
increasing burnout.
PMID- 29938575
TI - Positive psychological interventions for neurological disorders: a systematic
review.
AB - OBJECTIVES: Psychological well-being in people with neurological diseases can be
compromised due to brain damage or psychological reactions towards chronic
disabilities. This systematic review evaluated the efficacy of positive
psychological intervention (PPI) in neurological populations. METHODS: Previous
studies relevant to this topic were identified by searches in PUBMED, EMBASE,
MEDLINE, and PSYCINFO databases from Jan 1980 to August 2017. RESULTS: Of 1361
articles identified, 31 studies were included. Nineteen studies were randomized
controlled trials. Sixteen studies had sample sizes of less than 30. Twelve
studies were rated as high quality using the National Heart, Lung, and Blood
Institute (NHLBI) quality assessment tools. Six therapies were found: mindfulness
based approaches, positive savoring, life summary, expressive-based, hope-based
interventions, and character strengths. These interventions were shown to improve
quality of life, reduce symptomatic distress, and depressive symptoms.
CONCLUSION: PPIs promote well-being among patients with neurological deficits.
For PPIs to be considered as an evidence-based practice, more trials with
adequate statistical power are required.
PMID- 29938576
TI - Carbon nanotubes, but not spherical nanoparticles, block autophagy by a shape
related targeting of lysosomes in murine macrophages.
AB - Nanoparticles (NPs) can be toxic, depending on their physico-chemical
characteristics. Macroautophagy/autophagy could represent a potential underlying
mechanism of this toxicity. We therefore set up a study aimed to characterize in
depth the effects, on autophagy, of macrophage exposure to NPs, with a particular
attention paid to the role of NP physico-chemical characteristics (specifically
chemical composition, shape, size, length, crystal phase, and/or surface
properties). We demonstrate that exposure to carbon nanotubes (CNT) but not to
spherical NPs leads to the blockage of the autophagic flux. We further identified
lysosomal dysfunction, in association with the downregulation of SNAPIN
expression, as the underlying mechanism responsible for the CNT-induced autophagy
blockade. These results identify for the first time the shape as a major
determinant of the interaction of NPs with the autophagy pathway. Moreover,
identifying the lysosomes and SNAPIN as primary targets of MWCNT toxicity opens
new directions in the interpretation and understanding of nanomaterial toxicity.
PMID- 29938578
TI - TaqMan real-time RT-PCR assay for detecting Japanese encephalitis virus in swine
blood samples and mosquitoes.
AB - Japanese encephalitis (JE) is an emerging mosquito-borne zoonotic flaviviral
disease. The present study was undertaken with the objective to develop TaqMan
real-time reverse-transcription polymerase chain reaction (RT-PCR) assay for
rapid detection and quantification of Japanese encephalitis virus (JEV) in swine
blood and mosquito vectors. The amplification of envelope (E) gene was targeted
by designing gene-specific MGB TaqMan fluorescent probe along with the primers.
The best performance in terms of sensitivity was achieved by standardized TaqMan
real-time RT-PCR with a detection limit of 2.8 copies/reaction and it was found
to be 4-log more sensitive than conventional RT-PCR. The applicability of the
standardized TaqMan assay was evaluated by screening representative sets of field
swine blood samples and mosquito pools for JEV. The viral load ranged between
3.32 * 107-4.2 * 102 copies/ml of swine blood samples, and 5.7 * 109-1.3 * 102
copies/pool of mosquitoes. The standardized assay which is highly sensitive,
specific and rapid would aid in screening sentinel swine and mosquitoes under JEV
surveillance programs for effective prevention and control of disease in human
beings.
PMID- 29938579
TI - Does It All Stay in the (Normative) Family? Attitudes About Family Among Female
Jewish and Muslim Health-Profession Students in Israel.
AB - Family individualization occurs, if at all, at a different pace and to a
different extent in various societies and in various parts of society. Its impact
has led to new scholarship in the social and caring professions, for which the
concept of family is central in both professional education and practice. It is
assumed that attitudes toward changing marital norms, family forms, and family
relationships affect professionals' performance. This study, conducted in Israel
in 2014 with 157 female health-profession students-102 (65%) Jews and 55 (35%)
Muslim Arabs-focuses on attitudes about the family. Three patterns of attitudes
emerged: individualized traditionalism-a mix of traditional and individualized
attitudes, present among both the Jewish and the Muslim students; individualized
autonomy, present mostly among the Jewish students; and classic traditionalism,
present mostly among the Muslim students. Implications of these findings for the
education and practice of health care professionals are also discussed.
PMID- 29938577
TI - Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung
inflammation in CF mice.
AB - BACKGROUND: Cystic fibrosis (CF) lung infection is a complex condition where
opportunistic pathogens and defective immune system cooperate in developing a
constant cycle of infection and inflammation. The major pathogen, Pseudomonas
aeruginosa, secretes a multitude of virulence factors involved in host immune
response and lung tissue damage. In this study, we examined the possible anti
inflammatory effects of molecules inhibiting P. aeruginosa virulence factors.
METHODS: Pyocyanin, pyoverdine and proteases were measured in bacterial culture
supernatant from different P. aeruginosa strains. Inhibition of virulence factors
by sub-inhibitory concentrations of clarithromycin and by protease inhibitors was
evaluated. Lung inflammatory response was monitored by in vivo bioluminescence
imaging in wild-type and CFTR-knockout mice expressing a luciferase gene under
the control of a bovine IL-8 promoter. RESULTS: The amount of proteases,
pyocyanin and pyoverdine secreted by P. aeruginosa strains was reduced after
growth in the presence of a sub-inhibitory dose of clarithromycin. Intratracheal
challenge with culture supernatant containing bacteria-released products induced
a strong IL-8-mediated response in mouse lungs while lack of virulence factors
corresponded to a reduction in bioluminescence emission. Particularly, sole
inactivation of proteases by inhibitors Ilomastat and Marimastat also resulted in
decreased lung inflammation. CONCLUSIONS: Our data support the assumption that
virulence factors are involved in P. aeruginosa pro-inflammatory action in CF
lungs; particularly, proteases seem to play an important role. Inhibition of
virulence factors production and activity resulted in decreased lung
inflammation; thus, clarithromycin and protease inhibitors potentially represent
additional therapeutic therapies for P. aeruginosa-infected patients.
PMID- 29938580
TI - Complete mitogenome reveals genetic divergence and phylogenetic relationships
among Indian cattle (Bos indicus) breeds.
AB - Indigenous cattle of India belong to the species, Bos indicus and they possess
various adaptability and production traits. However, little is known about the
genetic diversity and origin of these breeds. To investigate the status, we
sequenced and analyzed the whole mitochondrial DNA (mtDNA) of seven Indian cattle
breeds. In total, 49 single-nucleotide variants (SNVs) were identified among the
seven breeds analyzed. We observed a common synonymous SNV in the COII gene
(m.7583G > A) of all the breeds studied. The phylogenetic analysis and genetic
distance estimation showed the close genetic relationship among the Indian cattle
breeds, whereas distinct genetic differences were observed between Bos indicus
and Bos taurus cattle. Our results indicate a common ancestor for European
Zwergzebu breed and South Indian cattle. The estimated divergence time
demonstrated that the Bos indicus and Bos taurus cattle lineages diverged 0.92
million years ago. Our study also demonstrates that ancestors of present zebu
breeds originated in South and North India separately ~30,000 to 20,000 years
ago. In conclusion, the identified genetic variants and results of the
phylogenetic analysis may provide baseline information to develop appropriate
strategies for management and conservation of Indian cattle breeds.
PMID- 29938582
TI - The testing effect and analogical problem-solving.
AB - Researchers generally agree that retrieval practice of previously learned
material facilitates subsequent recall of same material, a phenomenon known as
the testing effect. There is debate, however, about when such benefits transfer
to related (though not identical) material. The current study examines the
phenomenon of transfer in the domain of analogical problem-solving. In
Experiments 1 and 2, learners were presented a source text describing a problem
and solution to read which was subsequently either restudied or recalled.
Following a short (Experiment 1) or long (Experiment 2) delay, learners were
given a new target text and asked to solve a problem. The two texts shared a
common structure such that the provided solution for the source text could be
applied to solve the problem in the target text. In a combined analysis of both
experiments, learners in the retrieval practice condition were more successful at
solving the problem than those in the restudy condition. Experiment 3 explored
the degree to which retrieval practice promotes cued versus spontaneous transfer
by manipulating whether participants were provided with an explicit hint that the
source and target texts were related. Results revealed no effect of retrieval
practice.
PMID- 29938581
TI - AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to
trigger mitophagic cell death in glioma cells.
AB - : In most cases, macroautophagy/autophagy serves to alleviate cellular stress and
acts in a pro-survival manner. However, the effects of autophagy are highly
contextual, and autophagic cell death (ACD) is emerging as an alternative
paradigm of (stress- and drug-induced) cell demise. AT 101 ([-]-gossypol), a
natural compound from cotton seeds, induces ACD in glioma cells as confirmed here
by CRISPR/Cas9 knockout of ATG5 that partially, but significantly rescued cell
survival following AT 101 treatment. Global proteomic analysis of AT 101-treated
U87MG and U343 glioma cells revealed a robust decrease in mitochondrial protein
clusters, whereas HMOX1 (heme oxygenase 1) was strongly upregulated. AT 101
rapidly triggered mitochondrial membrane depolarization, engulfment of
mitochondria within autophagosomes and a significant reduction of mitochondrial
mass and proteins that did not depend on the presence of BAX and BAK1.
Conversely, AT 101-induced reduction of mitochondrial mass could be reversed by
inhibiting autophagy with wortmannin, bafilomycin A1 and chloroquine. Silencing
of HMOX1 and the mitophagy receptors BNIP3 (BCL2 interacting protein 3) and
BNIP3L (BCL2 interacting protein 3 like) significantly attenuated AT 101
dependent mitophagy and cell death. Collectively, these data suggest that early
mitochondrial dysfunction and HMOX1 overactivation synergize to trigger lethal
mitophagy, which contributes to the cell killing effects of AT 101 in glioma
cells. ABBREVIATIONS: ACD, autophagic cell death; ACN, acetonitrile; AT 101, (-)
gossypol; BAF, bafilomycin A1; BAK1, BCL2-antagonist/killer 1; BAX, BCL2
associated X protein; BH3, BCL2 homology region 3; BNIP3, BCL2 interacting
protein 3; BNIP3L, BCL2 interacting protein 3 like; BP, Biological Process; CCCP,
carbonyl cyanide m-chlorophenyl hydrazone; CC, Cellular Component; Con, control;
CQ, chloroquine; CRISPR, clustered regularly interspaced short palindromic
repeats; DMEM, Dulbecco's Modified Eagle Medium; DTT, 1,4-dithiothreitol; EM,
electron microscopy; ER, endoplasmatic reticulum; FACS, fluorescence-activated
cell sorting; FBS, fetal bovine serum; FCCP, carbonyl cyanide 4
(trifluoromethoxy)phenylhydrazone; GO, Gene Ontology; HAcO, acetic acid; HMOX1,
heme oxygenase 1; DKO, double knockout; LC-MS/MS, liquid chromatography coupled
to tandem mass spectrometry; LPL, lipoprotein lipase, MEFs, mouse embryonic
fibroblasts; mPTP, mitochondrial permeability transition pore; MTG, MitoTracker
Green FM; mt-mKeima, mito-mKeima; MT-ND1, mitochondrially encoded NADH:ubiquinone
oxidoreductase core subunit 1; PBS, phosphate-buffered saline; PE,
phosphatidylethanolamine; PI, propidium iodide; PRKN, parkin RBR E3 ubiquitin
protein ligase; SDS, sodium dodecyl sulfate; SQSTM1/p62, sequestome 1; STS,
staurosporine; sgRNA, single guide RNA; SILAC, stable isotope labeling with amino
acids in cell culture; TFA, trifluoroacetic acid, TMRM, tetramethylrhodamine
methyl ester perchlorate; WM, wortmannin; WT, wild-type.
PMID- 29938583
TI - Phenotyping pulmonary hypertension in systemic sclerosis: a moving target.
PMID- 29938584
TI - Early Shortening of Wrist Flexor Muscles Coincides With Poor Recovery After
Stroke.
AB - BACKGROUND: The mechanism and time course of increased wrist joint stiffness
poststroke and clinically observed wrist flexion deformity is still not well
understood. The components contributing to increased joint stiffness are of
neural reflexive and peripheral tissue origin and quantified by reflexive torque
and muscle slack length and stiffness coefficient parameters. OBJECTIVE: To
investigate the time course of the components contributing to wrist joint
stiffness during the first 26 weeks poststroke in a group of patients, stratified
by prognosis and functional recovery of the upper extremity. METHODS: A total of
36 stroke patients were measured on 8 occasions within the first 26 weeks
poststroke using ramp-and-hold rotations applied to the wrist joint by a robot
manipulator. Neural reflexive and peripheral tissue components were estimated
using an electromyography-driven antagonistic wrist model. Outcome was compared
between groups cross-sectionally at 26 weeks poststroke and development over time
was analyzed longitudinally. RESULTS: At 26 weeks poststroke, patients with poor
recovery (Action Research Arm Test [ARAT] <=9 points) showed a higher predicted
reflexive torque of the flexors ( P < .001) and reduced predicted slack length (
P < .001) indicating shortened muscles contributing to higher peripheral tissue
stiffness ( P < .001), compared with patients with good recovery (ARAT >=10
points). Significant differences in peripheral tissue stiffness between groups
could be identified around weeks 4 and 5; for neural reflexive stiffness, this
was the case around week 12. CONCLUSIONS: We found onset of peripheral tissue
stiffness to precede neural reflexive stiffness. Temporal identification of
components contributing to joint stiffness after stroke may prompt longitudinal
interventional studies to further evaluate and eventually prevent these
phenomena.
PMID- 29938585
TI - The Retrospective Evaluation of Positive and Negative Affect.
AB - A vast amount of literature examined the relationship between retrospective
affective evaluations and evaluations of affective experiences. This literature
has focused on simple momentary experiences, and was based on a unidimensional
concept of affect. The current article examines the relationships between
evaluations of complex experiences, experiences involving both positive and
negative feelings, and the retrospective evaluation of these experiences. Based
on the idea that negative information is better remembered than positive
information, we predict that in comparison with negative retrospective
evaluations, positive evaluations have a stronger correlation with end affect and
a weaker correlation with peak affect. These predictions are tested in two
studies. We explore boundary conditions for these effects and demonstrate the
implications of the asymmetry between positive and negative affect to various
topics that are at the center of affect research: the dimensionality of affective
experiences, the memory-experience gap, and the analysis of net affect.
PMID- 29938587
TI - Genetic diversity of autochthonous pig breeds analyzed by microsatellite markers
and mitochondrial DNA D-loop sequence polymorphism.
AB - The evaluation of the genetic structure of autochthonous pig breeds is very
important for conservation of local pig breeds and preservation of diversity. In
this study, 18 microsatellite loci were used to detect genetic relationship
between autochthonous pig breeds [Black Slavonian (BS), Turopolje pig (TP), and
Croatian wild boar] and to determine phylogenetic relationship among Croatian
autochthonous pig breeds and certain Asian and European pigs using the
mitochondrial DNA (mtDNA) D-loop sequence polymorphism. Relatively high degree of
genetic variation was found between the observed populations. The analysis of
mtDNA showed that haplotypes of the studied pig populations are different from
the other European and Chinese haplotypes. BS pigs showed some similarities with
Mangalitsa and Duroc breeds. The genetic distances of TP can be explained by high
degree of inbreeding during the past century. Despite the European origin of
Croatian pig breeds with some impact of Chinese breeds in the past, the results
of present study show that genetic diversity is still pronounced within
investigated breeds. Furthermore, the genetic diversity is even more pronounced
between Croatian breeds and other European and Chinese pig breeds. Thus,
conservation of Croatian pig breeds will contribute to overall genetic diversity
preservation of pig breeds.
PMID- 29938586
TI - Releasing the tether: Weight normalization following corrective spinal fusion in
cerebral palsy.
AB - PURPOSE: Feeding difficulties are common among patients with cerebral palsy (CP)
and neuromuscular (NM) scoliosis. We theorize that posterior spinal fusion (PSF)
reduces intra-abdominal pressure, resulting in improved feeding and subsequent
weight gain. We hypothesized that, among nonambulatory patients with CP and NM
scoliosis, we would observe significant gain in weight following PSF. METHODS:
Fifty subjects with nonambulatory CP who underwent PSF for NM scoliosis were
included. Age and weight were recorded for the preoperative year; on the day of
surgery; and at 6-month, 1-year, and 2-year follow-up. Weights were converted to
weight percentiles using CP-specific growth charts. The weight percentile
distributions were compared between time points using descriptive statistics as
well as regression analysis. RESULTS: The average change in weight from the day
of surgery to 2-year follow-up was +3.4 percentiles. Patients who started out
under the 50th percentile gained an average of 17.3 percentiles in the first year
after PSF ( p = 0.009). Regression analysis showed that patients with baseline
weight <50th percentile tended to gain in weight percentile over the first
postoperative year ( beta = 1.990, p = 0.001). No trend was present among this
group prior to surgery ( p = 0.692) or during the second postoperative year ( p =
0.945). No trends were noted prior to or after surgery for patients with baseline
weights >=50th percentile. No significant association was observed between curve
severity (measured by preoperative Cobb angle) and weight change. CONCLUSIONS:
This series is the first to document significant weight gain after PSF for NM
scoliosis, supporting the theory that spinal correction improves digestive
function. LEVEL OF EVIDENCE: Prognostic level II.
PMID- 29938588
TI - Key determinants of time to 5 m in different ventral swimming start techniques.
AB - The aim of this study was to determine the biomechanical parameters that explain
ventral start performance in swimming. For this purpose, 13 elite swimmers
performed different variants of the ventral start technique. Two-dimensional
video analyses of the aerial and underwater phases were used to assess 16
kinematic parameters from the starting signal to 5 m, and an instrumented
starting block was used to assess kinetic data. A Lasso regression was used to
reduce the number of parameters, providing the main determinants to starting
performance, revealing different combinations of key determinants, depending on
the variant (r2 >= 0.90), with flight distance being the most relevant to all
variants (r <= -0.80; p < .001). Also, special attention should be given to the
total horizontal impulse in the grab start (r = -0.79; p < .001) and to the back
foot action in the track and kick starts (r <= 0.61; p < .001). In addition, we
provide two equations that could be easily used to predict starting performance
by assessing block time and flight time (r2 = 0.66) or block time and flight
distance (r2 = 0.83). These data provide relevant contributions to the further
understanding of the biomechanics of swimming starts as well as insights for
performance analysis and targeted interventions to improve athlete performance.
PMID- 29938589
TI - Performance monitoring of self and other in a turn-taking piano duet: A dual-EEG
study.
AB - During joint action tasks, expectations for outcomes of one's own and other's
actions are collectively monitored. Recent evidence suggests that trait empathy
levels may also influence performance monitoring processes. The present study
investigated how outcome expectation and empathy interact during a turn-taking
piano duet task, using simultaneous electroencephalography (EEG) recording.
During the performances, one note in each player's part was altered in pitch to
elicit the feedback-related negativity (FRN) and subsequent P3 complex. Pianists
memorized and performed pieces containing either a similar or dissimilar sequence
as their partner. For additional blocks, pianists also played both sequence types
with an audio-only computer partner. The FRN and P3a were larger in response to
self than other, while P3b occurred only in response to self, suggesting greater
online monitoring of self- compared to other-produced actions during turn-taking
joint action. P3a was larger when pianists played a similar sequence as their
partner. Finally, as trait empathy level increased, FRN in response to self
decreased. This association was absent for FRN in response to other. This may
reflect that highly-empathetic musicians during joint performance could use a
strategy to suppress exclusive focus on self-monitoring.
PMID- 29938591
TI - FOXO3 links autophagy to apoptosis.
AB - The molecular machinery linking macroautophagy (autophagy hereafter) to apoptosis
is still being elucidated. A recent study found that the transcription factor
FOXO3/FOXO3A (forkhead box O3), which regulates autophagy, is itself regulated by
basal autophagy to determine apoptosis sensitivity. Autophagy inhibition confers
cell sensitivity to anti-cancer agents, and this effect is explained by the
ability of FOXO3 to transactivate the pro-apoptotic gene BBC3/PUMA. Here, we
discuss the possibility that FOXO3 acts as a cell surveillance mechanism to
correct autophagy perturbations (i.e., autophagy inhibition), and confers
apoptosis sensitization if this autophagy imbalance is not rectified.
PMID- 29938590
TI - Non-invasive right ventricular load adaptability indices in patients with
scleroderma-associated pulmonary arterial hypertension.
AB - Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is associated
with worse outcome than idiopathic pulmonary arterial hypertension (IPAH),
potentially due to worse right ventricular adaptation to load as suggested by
pressure-volume loop analysis. The value of non-invasive load-adaptability
metrics has not been fully explored in SSc-PAH. This study sought to assess
whether patients with incident SSc-PAH have worse echocardiographic load
adaptability metrics than patients with IPAH. Twenty-two patients with incident
SSc-PAH were matched 1:1 with IPAH based on pulmonary vascular resistance.
Echocardiographic load-adaptability indices were divided into: surrogates of
ventriculo-arterial coupling (e.g. right ventricular area change/end-systolic
area), indices reflecting the proportionality of load adaptation (e.g. tricuspid
regurgitation velocity-time integral normalized for average right ventricular
radius), and simple ratios (e.g. tricuspid annular plane systolic excursion/right
ventricular systolic pressure). The prognostic value of these indices for
clinical worsening (i.e. death, transplant, or hospitalization for heart failure)
at one year was explored. The two groups were comprised of patients of similar
age, with similar cardiac index, pulmonary resistance, capacitance and NT-proBNP
levels ( p > 0.10). There was no difference in baseline right ventricular
dimension, function or load-adaptability indices. At one year, eight (36.4%) SSc
PAH patients had experienced clinical worsening (eight hospitalizations and two
deaths) versus one hospitalization in the IPAH group. Load adaptation at one year
in survivors was not worse in SSc-PAH ( p > 0.33). Patients with IPAH responded
better to therapy than SSc-PAH in terms of reduction of right ventricular areas
at one year ( p < 0.05). Right ventricular load-adaptability echocardiographic
indices do not appear to capture the increased risk of negative outcomes at one
year associated with SSc-PAH.
PMID- 29938592
TI - Influence of single nucleotide polymorphisms in pri-miR-124-1 and STAT3 genes on
gastric cancer susceptibility.
AB - INTRODUCTION: MicroRNAs (miRNAs) are small ribonucleic acids that modulate the
expression of downstream target genes. There is considerable evidence of their
involvement in many malignancies, such as oesophageal and gastric. We
hypothesised altered expressions of pri-miR-124-1 rs531564 and STAT3 rs1053023
polymorphisms in gastric cancer. MATERIALS AND METHODS: Genomic DNA was extracted
from peripheral blood of 250 patients with gastric cancer and 310 healthy
individuals. The RFLP method was applied for determination of pri-miR-124
polymorphism and the AS-PCR method for STAT3 polymorphism. RESULTS: The
distribution of rs531564 genotypes in cases and controls was different: the G
allele carriers had a reduced gastric cancer risk (OR = 0.62; 95%CI = 0.49-0.80,
P = 0.0002). Presence of the minor allele of STAT3 (rs1053023) was linked with
higher risk of gastric cancer (OR = 2.29; 95% CI = 1.79-2.93, P < 0.0001).
Compared with the most frequent haplotype C-G [the SNP order was pri-miR-124-1
(rs531564) and STAT3 (rs1053023)] in controls, C-A haplotype was associated with
a significantly increased risk of gastric cancer (OR = 2.28; 95%CI = 1.64-3.09, P
< 0.0001). CONCLUSION: There is a strong link between pri-miR-124-1 rs531564 and
STAT3 rs1053023 and gastric cancer that may be pathogenic, and so worthy of
further investigation.
PMID- 29938593
TI - Macrophage Populations and Expression of Regulatory Inflammatory Factors in
Hepatic Macrophage-depleted Rat Livers under Lipopolysaccharide (LPS) Treatment.
AB - To investigate the significance of the appearance of hepatic macrophages and
expression of inflammatory factors in normal and macrophage-depleted livers,
hepatic macrophages were depleted with liposome (Lipo)-encapsulated clodronate
(CLD; 50 mg/kg, i.v.) followed by lipopolysaccharide (LPS) administration (0.1
mg/kg, i.p.) in F344 rats (CLD + LPS). Vehicle control rats (Lipo + LPS) received
empty-Lipo before LPS. The low dose of LPS did not result in microscopic changes
in the liver in either treatment group but did modulate M1 and M2 macrophage
activity in Lipo + LPS rats without altering repopulating hepatic macrophages in
CLD + LPS rats. LPS treatment in Lipo + LPS rats dramatically increased the M1
(IL-1beta, IL-6, TNF-alpha, and MCP-1) but not M2 macrophage-related factors (IL
4 and CSF-1) compared to CLD + LPS rats. In the CLD + LPS rats, the M2 macrophage
related factors IL-4 and CSF-1 were elevated. In conclusion, low-dose LPS
activated hepatic macrophages in rat livers without causing liver injury or
stimulating repopulating hepatic macrophages. These data suggest that LPS may
alter the liver microenvironment by modulating M1 or M2 macrophage-related
inflammatory mediators and macrophage-based hepatotoxicity.
PMID- 29938594
TI - A systematic review of the impact of outpatient clinical pharmacy services on
medication-related outcomes in patients receiving anticancer therapies.
AB - BACKGROUND: Patients receiving anticancer therapies are frequently prescribed
complex and high-risk medication regimens, which at times can result in
medication misadventures. The objective of this review was to assess the effect
of outpatient clinical pharmacy services on medication-related outcomes in
patients receiving anticancer therapies, including patients undergoing
radiotherapy. METHODS: A systematic review of original publications indexed in
EMBASE, MEDLINE and Cochrane Library from June 2007 to June 2017. Eligible
studies evaluated outpatient pharmacy clinic services for cancer patients and
reported at least one medication-related quantitative outcome measure. Two
authors independently reviewed full-text articles for inclusion, then extracted
data and performed quality and risk of bias assessments. RESULTS: Of 908
identified publications, 13 met predefined eligibility criteria; 1 randomised
control trial, 2 controlled cohort studies and 10 uncontrolled before-after
studies. Many excluded studies described outpatient pharmacy services but lacked
medication-related outcomes. All included studies had informative practice model
designs, with interventions for drug-related problems including drug dose
optimisation ( n = 8), reduced drug interaction ( n = 6) and adverse drug
reaction reporting ( n = 3). Most studies ( n = 11) reported on symptom
improvement, commonly nausea ( n = 7) and pain ( n = 5). Of four studies in
radiotherapy cohorts, pharmacist involvement was associated with improved
symptoms, satisfaction and wellbeing scores. CONCLUSION: Few studies have
objectively assessed outpatient pharmacy cancer services, even fewer in the
radiotherapy settings. Although the results support these services, significant
heterogeneity and bias in the study designs prohibit robust conclusions and
further controlled trials are required.
PMID- 29938595
TI - Perceptions of Cyberstalking: Impact of Perpetrator Gender and
Cyberstalker/Victim Relationship.
AB - Cyberstalking is a relatively new phenomenon with limited empirical research.
Consequently, despite the seriousness of the crime, prevalence rates are
unreliable and estimates suffer from vast variation. Cyberstalking is likely to
be underreported due to limited community understanding of what behaviors
constitute cyberstalking. There are many factors unique to cyberstalking which
may impact the extent to which the crime is reported, and the extent to which the
perpetrator or victim is held responsible. The current study aimed to examine the
impact of perpetrator gender, and the relationship between the perpetrator and
victim (ex-intimate vs. stranger) on perceptions of cyberstalking. Participants
read one of four scenarios, designed for this study, which varied in victim
gender and cyberstalker-victim relationship. Perpetrator gender impacted
perceptions of the scenario, such that the male perpetrator was viewed as more
dangerous. Scenarios with a male perpetrator were perceived as more consistent
with cyberstalking and the behavior as illegal in nature. Victim gender was found
to impact the amount of blame a victim receives, such that the female victim was
attributed less blame than the male victim. Meanwhile, the male victim was blamed
more for the occurrence of the cyberstalking behavior, and their claims as a
victim were taken less seriously and perceived as less legitimate. Finally,
participant gender was found to impact perceptions toward the cyberstalking
scenarios.
PMID- 29938596
TI - Hyperinflation of Vasopressors (Vasopressin, Norepinephrine, Ephedrine, etc).
AB - PURPOSE: Hyperinflation refers to the increasing cost of drugs which occurs due
to continued drug shortages and rebranding. Hyperinflation has significant
implications in increasing overall healthcare costs with reduced reimbursement,
increased patient acuity, and an aging population, but published strategies to
reduce costs and minimize waste are limited. OBJECTIVE: To describe the
hyperinflation and cost mitigation strategies of three vasopressor medications,
vasopressin, epinephrine, and ephedrine. CONCLUSION: The steep increase in
medications is expected to continue, and mitigation strategies to reduce waste
and select the most cost effective therapy to offset the price increase is
crucial for healthcare systems.
PMID- 29938599
TI - Representational Bias in the Radial Axis in Children With Dyslexia: A Landmarks
Alignment Study.
AB - To better identify the distinctive characteristics of space representation in the
radial dimension, we have proposed a new paradigm: the landmarks alignment task
where two parallel aluminum bars were radially presented. Children had to move a
landmark along one bar and place it at the same location as the reference
landmark placed by the examiner on the parallel bar. The major interest of this
task was its capacity to assess space representation in the radial dimension when
considering a spatial landmark that oriented the subject's attention toward the
orthogonal dimension. The most important result showed that in the radial
dimension children with dyslexia exhibited a forward bias on the left bar,
meaning a mental underrepresentation of the leftward peripersonal space and/or a
mental overrepresentation of the rightward peripersonal space. Furthermore,
reading discrepancies were correlated with radial forward bias on the left bar.
The experiment was also conducted in the lateral axis, showing a pseudoneglect
behavior in children without dyslexia. Our landmarks alignment task had the
advantage of being able to assess space representation in a complex environment.
The forward radial representational bias in children with dyslexia could have
implications for spatial orientation in peripersonal workspace in school
situations.
PMID- 29938597
TI - Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research
Excellence: supporting the next generation of autophagy researchers and fostering
international collaborations.
AB - Recently, NIH has funded a center for autophagy research named the Autophagy,
Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence,
located at the University of New Mexico Health Science Center (UNM HSC), with
aspirations to promote autophagy research locally, nationally, and
internationally. The center has 3 major missions: (i) to support junior faculty
in their endeavors to develop investigations in this area and obtain independent
funding; (ii) to develop and provide technological platforms to advance autophagy
research with emphasis on cellular approaches for high quality reproducible
research; and (iii) to foster international collaborations through the formation
of an International Council of Affiliate Members and through hosting national and
international workshops and symposia. Scientifically, the AIM center is focused
on autophagy and its intersections with other processes, with emphasis on both
fundamental discoveries and applied translational research.
PMID- 29938598
TI - Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by
targeting MIR142-TIPARP: implications for cerebral ischemic stroke.
AB - : Circular RNAs (circRNAs) are highly expressed in the central nervous system and
are involved in the regulation of physiological and pathophysiological processes.
However, the potential role of circRNAs in stroke remains largely unknown. Here,
using a circRNA microarray, we showed that circular RNA Hectd1 (circHectd1)
levels were significantly increased in ischemic brain tissues in transient middle
cerebral artery occlusion (tMCAO) mouse stroke models and further validated this
finding in plasma samples from acute ischemic stroke (AIS) patients. Knockdown of
circHectd1 expression significantly decreased infarct areas, attenuated neuronal
deficits, and ameliorated astrocyte activation in tMCAO mice. Mechanistically,
circHECTD1 functions as an endogenous MIR142 (microRNA 142) sponge to inhibit
MIR142 activity, resulting in the inhibition of TIPARP (TCDD inducible poly[ADP
ribose] polymerase) expression with subsequent inhibition of astrocyte activation
via macroautophagy/autophagy. Taken together, the results of our study indicate
that circHECTD1 and its coupling mechanism are involved in cerebral ischemia,
thus providing translational evidence that circHECTD1 can serve as a novel
biomarker of and therapeutic target for stroke. ABBREVIATIONS: 3-MA: 3
methyladenine; ACTB: actin beta; AIS: acute ischemic stroke; AS: primary mouse
astrocytes; BECN1: beclin 1, autophagy related; BMI: body mass index; circHECTD1:
circRNA HECTD1; circRNAs: circular RNAs; CBF: cerebral blood flow; Con: control;
DAPI: 4',6-diamidino-2-phenylindole; ECA: external carotid artery; FISH:
fluorescence in situ hybridization; GAPDH: glyceraldehyde-3-phosphate
dehydrogenase; Gdna: genomic DNA; GFAP: glial fibrillary acidic protein; GO: gene
ontology; HDL: high-density lipoprotein; IOD: integrated optical density; LDL:
low-density lipoprotein; LPA: lipoprotein(a); MAP1LC3B: microtubule-associated
protein 1 light chain 3 beta; MIR142: microRNA 142; mNSS: modified neurological
severity scores; MRI: magnetic resonance imaging; NIHSS: National Institute of
Health Stoke Scale; OGD-R: oxygen glucose deprivation-reperfusion; PCR:
polymerase chain reaction; PFA: paraformaldehyde; SQSTM1: sequestosome 1; TIPARP:
TCDD inducible poly(ADP-ribose) polymerase; tMCAO: transient middle cerebral
artery occlusion; TTC: 2,3,5-triphenyltetrazolium chloride; UTR: untranslated
region; WT: wild type.
PMID- 29938600
TI - A p37-based ELISA used to monitor anti- Mycoplasma hyorhinis IgG in serum from
pigs immunized with inactivated M. hyorhinis vaccines.
AB - Mycoplasma hyorhinis is an important pathogen of swine that can often occur as a
respiratory coinfection with viral pathogens, but can also cause arthritis and
polyserositis in infected animals. To date, no assay is available to assess the
serologic response to M. hyorhinis vaccines, to our knowledge. We used
recombinantly expressed M. hyorhinis p37 protein to monitor the magnitude of the
IgG response in vaccinated animals. The assay was able to distinguish animals
vaccinated with M. hyorhinis from those vaccinated with the other important
Mycoplasma species: M. hyopneumoniae and M. hyosynoviae. When formulated with an
ideal adjuvant, inactivated vaccines designed to protect animals against M.
hyorhinis induced a measurable and dose-dependent antibody response against the
p37 protein. Additionally, the protein appears to be highly conserved between
strains of M. hyorhinis isolated in the United States. The specificity of the
assay as well as the conservation and immunogenicity of the p37 protein make it
an ideal candidate antigen for use in measuring the immune response against M.
hyorhinis after vaccination in weaned pigs.
PMID- 29938601
TI - Grieving Styles of Young Banso Widows.
AB - Grieving is manifested differently around the world depending on culture, social
desirability, and social norms. Little is known about grieving patterns in
Africa. As such, a study of the grieving patterns of young widows of the Banso
tribe of the Cameroon was conducted. This examination used Doka and Martin's
model of grieving styles as the lens for this research. This model delineates a
continuum of grief styles: instrumental on one end, intuitive on the other, and
blended in the middle. This study used the validated Grief Pattern Inventory to
determine if young Banso widows in this sample are intuitive, instrumental, or
blended grievers. The study employed a cross-sectional design. The results
indicated that 47% of the participants were intuitive grievers and 41% were
blended grievers. Policy, research, and clinical implications emerging from the
results were presented.
PMID- 29938602
TI - Constructing and Expanding Suicide Narratives From Gay Men.
AB - In this study, we document life stories of gay men who attempted suicide as
adults. Our goal is to expand the collection of narratives used to understand
this persistent health inequity. We interviewed seven adult gay men, each of whom
had attempted suicide two to four times, and identified five narratives. Pride
narratives resist any connection between sexuality and suicide. Trauma-and-stress
narratives enable coping through acknowledgment of sexual stigma as a fundamental
trauma and cause of subsequent stress and suicidal thoughts. Memorial narratives
prevent suicide by maintaining a strong sense of "permanent" identity. Outing
narratives demand that the listener confronts the legacy of unjust practices of
homosexual surveillance and "outing," which historically resulted in gay
suicides. Finally, postgay narratives warn of the risk of suicide among older
generations of gay men who feel erased from the goals of modern gay movements.
Sexual identity concealment or invisibility featured prominently in all five
narratives.
PMID- 29938603
TI - Robotic Camera Assistance: The Future of Laparoscopic and Thoracoscopic Surgery?
AB - INTRODUCTION: Minimally invasive techniques have become the standard for a
variety of procedures across all surgical specialties. There has been a recent
move to integrate robotic technology into standard laparoscopic and thoracoscopic
surgery with the aim of improving stability of the visual field with the use of
robotic camera assistance. The aim of this study was to report on and examine the
use of a headset-controlled robotic camera holder, FreeHand. METHODS: Between May
2013 and Dec 2016, 105 procedures were observed where the FreeHand robotic camera
assistant was used. Observations were made of 43 consultant surgeons in 30
hospitals performing 21 different surgical procedures. During the surgery, the
number of scope cleans and collisions were quantified, and surgeons were asked to
score from 0 to 5 the setup, ergonomics, usability, and overall experience in a
questionnaire. RESULTS: Overall surgeon satisfaction was rated as "good" for
setup (4.29), ergonomics of the system (4.12), usability (4.39), and overall
experience of the system (4.34). In 8 operations (7.6%), there was a conversion
from robotic camera assistant to manual assistant. There were no reported adverse
events attributable to the use of the system. CONCLUSION: This study demonstrates
the breadth of surgical procedures that can be performed with a robotic camera
assistant. The robotic camera assistant was found to be safe and simple to use
and was positively perceived on assessment in multiple procedures spanning
several surgical specialties. This work suggests that robotic camera assistants
may offer significant benefits to laparoscopic and thoracoscopic surgeons.
PMID- 29938604
TI - Adipose tissue lipolytic inhibition enhances the glucoregulatory properties of
exercise in type 2 diabetes patients.
AB - AIMS: Exercise combined with adipose tissue lipolytic inhibition augments
intramuscular lipid and glycogen use in type 2 diabetes patients. The present
study investigates the impact of adipose tissue lipolytic inhibition during
exercise on subsequent postprandial glycemic control in type 2 diabetes patients.
METHODS: Fourteen male type 2 diabetes patients (age 65 +/- 2 years, HbA1c 6.7 +/
0.1% (50 +/- 2 mmol/mol)) participated in a double-blind placebo-controlled
randomized cross-over study in which subjects performed endurance-type exercise
after being administered 250 mg of a nicotinic acid analogue (acipimox; ACP) or a
placebo (PLA). A control experiment was included in which no exercise was
performed (CON). RESULTS: Sixty minutes of endurance-type exercise (at 45% Wpeak)
did not significantly lower circulating plasma glucose and insulin excursions in
PLA when compared with CON (P = .300). Acipimox administration strongly reduced
circulating plasma FFA concentrations during exercise (P < .001). Circulating
plasma glucose and insulin excursions were substantially lower during 7.5 h of
recovery from exercise (i.e. postprandial) in ACP when compared with either CON
(P = .041 and P = .002, respectively) or PLA (P = .009 and P = .001,
respectively). CONCLUSIONS: Collectively, exercise with adipose tissue lipolytic
inhibition reduces postprandial blood glucose and insulin excursions and, as
such, further improves glycemic control in male type 2 diabetes patients.
PMID- 29938605
TI - Tubular surgery with the assistance of endoscopic surgery via a paramedian or
midline approach for lumbar spinal canal stenosis at the L4/5 level.
AB - BACKGROUND: Lumbar spinal canal stenosis surgery has recently improved with the
use of minimally invasive techniques. Less invasive procedures have emerged, and
microendoscopic decompression through smaller incisions is frequently performed.
Tubular surgery with the assistance of endoscopic surgery procedures has led to
particularly remarkable changes in surgery, with reduced tissue trauma and
morbidity. PURPOSE: The purpose of this study was to compare the clinical
outcomes of two different minimally invasive decompressive surgical techniques
(microendoscopic bilateral decompression surgery using the unilateral approach
[microendoscopic laminectomy (MEL)] and microendoscopy-assisted muscle-preserving
interlaminar decompression (MILD; ME-MILD)) using spinal endoscopy for lumbar
spinal canal stenosis measured using a visual analog scale (VAS), the Japanese
Orthopedic Association (JOA) score, and the JOA Back Pain Evaluation
Questionnaire (JOABPEQ), which is based on a patient-oriented scoring system.
STUDY DESIGN: This study was a retrospective review of prospectively collected
surgical data. METHODS: The study included 81 patients (MEL 39 patients, 20 men
and 19 women, mean age 68.9 years; and ME-MILD 42 patients, 22 men and 20 women,
mean age 73.1 years) with lumbar spinal stenosis (LSS). The indications for
surgery were moderate-to-severe stenosis, persistent neurological symptoms, and
failure of conservative treatment over 3 months, with a JOA score under 15 points
or intermittent claudication at 100 m. This study included patients having LSS at
a single vertebral level (L4/5). RESULTS: Low back pain, buttock-leg pain, and
numbness were significantly improved in terms of the VAS score from 3 months with
both MEL and ME-MILD. In all periods, JOA scores over 3 years of follow-up were
significantly higher than those obtained before surgery with both MEL and ME
MILD, and there were improvements of low back pain and walking function.
CONCLUSIONS: These observations demonstrate that ME-MILD is a safe and very
effective minimally invasive technique for degenerative LSS, similar to MEL.
PMID- 29938607
TI - Reflections on the Use of Audio Diaries to Access Young People's Lived
Experiences of HIV in Zimbabwe.
AB - This methodological article reflects on the contribution audio diaries can make
to accessing important, and commonly silenced, dimensions of the lived experience
of growing up with HIV and their acceptability to children. Audio diaries were
used by 12 young people, aged 11 to 13 years, as part of a longitudinal
qualitative study embedded within the Anti-Retroviral Research for Watoto (ARROW)
clinical trial. The method provided an alternative means for young people to
express detailed reflections on their day-to-day encounters, as well as
ordinarily silenced topics, including hidden and suppressed emotions regarding
the circumstance surrounding their perinatal infection. Although the audio diary
has great potential as method, its efficacy rests on young people's understanding
of how to use it. There are ethical challenges around maintaining confidentiality
while participants are in possession of the diaries and provision of appropriate
support. The technology used in the study was in many ways cumbersome compared
with opportunities increasingly available.
PMID- 29938606
TI - Influence of the AT1 Receptor Antagonists Telmisartan and Losartan on
Reproduction and Offspring After Paternal Exposure to Ionizing Radiation.
AB - This study evaluated the repercussions of paternal exposure to radiation on
reproduction and offspring in rats, as well as whether treatment with the
angiotensin II type 1 (AT1) receptor antagonists telmisartan and losartan has a
mitigating effect. Rats were randomly divided into 6 groups: control, radiation,
telmisartan, losartan, radiation + telmisartan, and radiation + losartan. A
single 5 Gy dose of radiation was administered directly into the scrotum,
followed by treatment with telmisartan (12 mg/kg/d) or losartan (34 mg/kg/2 times
per day) for 60 days in the groups receiving these medications. The reproductive
ability of the test animals was assessed before and after exposure to radiation
via fertility tests. The resulting offspring were analyzed for the presence of
external and internal anomalies. Ionizing radiation significantly affected the
rates of fertility, pre- and postimplantation losses, and implantation.
Telmisartan and losartan did not significantly prevent this radiation-induced
damage. The frequency of fetal anomalies was similar in offspring produced before
and after paternal radiation exposure. Moreover, irradiated rats that received
treatments and were able to generate offspring did not produce fetuses with
morphological changes; this may represent a possible radioprotective effect AT1
antagonists have on offspring development, although few fetuses survived and were
evaluated for malformations. Although the study findings indicate that these
medications have a positive effect, further studies with longer treatment periods
(extending beyond 1 rat spermatogenic cycle) are needed to determine whether
these drugs significantly improve reproductive rates after paternal exposure to
radiation, which may also reflect an increase in the number of viable fetuses.
PMID- 29938608
TI - The Imperative for a Triumph-Over-Tragedy Story in Women's Accounts of Undergoing
Chemotherapy for Ovarian Cancer.
AB - We aimed to examine how women construct their experiences of chemotherapy
treatment for ovarian cancer. Through semistructured interviews, we explored the
accounts of 18 Australian women about their experiences within a broader cultural
imperative-or discourse-to "think positively." By applying a critical realist
lens to the analysis, we identified two discursive themes that shaped women's
accounts. The "feeling different and managing support" theme highlights the
identity challenges women faced because of the lack of formal support for ovarian
cancer. Conversely, the theme "women's reconstructions of difficult experiences"
illustrates the imperative for women to present a positive story as a way of
restoring their position of a lucky and stoic survivor. Such speaking served to
mask some of the underlying difficulties that were part of these women's
experiences. Health care professionals need to consider looking for the hidden
stories of vulnerability that lie beneath the triumphant ones.
PMID- 29938609
TI - Who Is Less Likely to Ostracize? Higher Trait Mindfulness Predicts More
Inclusionary Behavior.
AB - Despite the pain ostracism (being excluded and ignored) causes, researchers have
minimally investigated factors related to reducing its occurrence. We
investigated the association between higher trait mindfulness (the tendency to be
attentive to the present moment) and lower engagement in ostracism. In Study 1,
employed adults scoring higher on trait mindfulness reported ostracizing
coworkers less. In Study 2, participants possessing higher levels of trait
mindfulness demonstrated greater inclusion of a fellow group member being
ostracized by others in the group. Results suggested that attention, rather than
empathy, was the psychological process responsible for greater inclusion of an
ostracized group member by mindful individuals. Study 3 supported this conclusion
because participants responded similarly to those high in trait mindfulness when
they were instructed to pay attention and ensure all players were included
equally. Overall, we found that people with higher levels of trait mindfulness
are more attentive to targets of ostracism.
PMID- 29938610
TI - Coronary Microvascular and Cardiac Dysfunction Due to Homocysteine
Pathometabolism; A Complex Therapeutic Design.
AB - In various metabolic diseases, both the coronary circulation and cardiac
metabolism are altered. Here we summarize the effects of a condition called
hyperhomocysteinemia (HHcy) - which can develop due to genetic and/or
environmental causes - on the function of coronary microvessels and heart. This
metabolic disease is underappreciated, yet even mild or moderate elevation of
plasma concentrations of homocystein (Hcy, plasma Hcy >16 uM), a sulfur
containing amino acid produced via methionine metabolism) leads to coronary and
peripheral artery and even venous vessel diseases, eliciting vasomotor
dysfunction and increased thrombosis, consequently increased morbidity and
mortality. Yet the underlying mechanisms have not yet been revealed. Recent
studies indicated that there are common pathomechanisms, which may affect several
cellular functions. With methionin diet-induced HHcy two main pathomechanisms
were revealed: the dysfunction of nitric oxide (NO) pathway resulting in reduced
dilator responses of arteries and arterioles, and the simultaneously increased
thromboxane A2 (TXA2) activity both in vessels and platelets. These changes are
likely due to an increased production of reactive oxidative species (oxidative
stress) due to increased NADPH oxidase assembly, which eventually lead to
inflammatory processes (indicated by increases in TNFalpha, NFkappabeta, p22phox,
p67phox, and rac-1, levels) and changes in various gene expressions and
morphological remodeling of vessels. Increased superoxide production and reduced
availability of NO alter the regulation of mitochondrial function in the
myocardium. The interactions of these pathomechanisms may explain why HHcy
increases the uptake of glucose and lactate and decreases the uptake of free
fatty acid by the heart. The pathological consequences of HHcy could be worsening
by the simultaneous presence of other risk factors, such as hyperlipidemia,
diabetes mellitus and metabolic syndrome. All in all, HHcy and associated
pathometabolism lead to severe changes and dysfunctions of coronary arterial
vessels and cardiac function, which may not always be apparent in clinical
settings but most likely contribute to the increased prevalence of cardiovascular
diseases and mortality, which however can be reduced by appropriate prevention
and treatments. We believe that HHcy is an underestimated - likely due to
inappropriate clinical trials - but serious disease condition because it promotes
the development of atherosclerosis in large arterial vessels, vasomotor
dysfunction in microvessels, hypertension and thrombosis. In this review, we will
summarize previous functional findings focusing on coronary vessels and cardiac
function and the underlying cellular and molecular mechanisms enabling the
development of novel treatments.
PMID- 29938611
TI - Coronary Microcirculation in Ischemic Heart Disease.
AB - BACKGROUND: Ischemic heart disease has long been considered to be exlusively
caused by stenosis or occlusion. However, the coronary microcirculation too may
play an important role in ischemic conditions. Also, the crucial role of
microvessels in not only regulating blood flow on a local level but also
mediating vascular permeability or inflammatory responses has been recognized.
OBJECTIVE: To review important physiological and pathophysiological mechanisms of
coronary microcirculatory control with focus on heterogeneity of local perfusion,
microvascular permeability and inflammation. METHOD: Selective research of the
literature. RESULTS: Heterogeneity is a characteristic of microvascular networks
and affects structural and functional parameters such as vessel diameter, length,
and connection pattern, flow velocity, wall shear stress, and oxygenation.
Microvascular networks are optimized to meet the metabolic demand of all tissue
compartments. This requires continuous vascular adaptation regulated by local
hemodynamic and metabolic stimuli. Compromising this regulation results in
functional arterio-venous shunting and tissue areas with either hyperperfusion or
hypoxia in close proximity. In ischemia-reperfusion, increased microvascular
permeability may aggravate tissue hypoxia by increasing extravascular pressure
and seems to contribute to adverse myocardial remodeling. Transendothelial
transport mechanisms and deterioration of the endothelial glycocalyx seem to be
major contributors to tissue edema. Also in the context of ischemia-reperfusion,
an inflammatory response mediated by venular endothelium expressing specific
adhesion molecules contributes to tissue injury. However, anti-inflammatory
therapies failed in clinical studies and a multi-targeted approach for cardiac
protection is required. CONCLUSION: Disturbances of the coronary microcirculation
are involved in different pathophysiological aspects of reperfusion injury.
PMID- 29938612
TI - Microcirculation and Heart Failure.
AB - The idea of coronary microcirculation playing a role in the pathophysiology of
heart failure dates from decades ago, with authors hypothesizing that structural
and functional alterations in the coronary microcirculation could potentially
contribute to heart failure. It is known that in a wide range of primary
cardiomyopathies, from dilated to hypertrophic, there are pathological
alterations in myocardial vasculature structure and function, playing a role in
the clinical course of the disease. Needless to say, many patients with normal
epicardial coronary arteries can suffer from coronary microvascular dysfunction,
that could lead to a wide variety of clinical problems - from impaired functional
capacity to stable and unstable angina, Takotsubo syndrome, myocardial infarction
with normal coronary arteries and can also end up with either acute or chronic
heart failure. Furthermore, nowadays, it has been recognized that pathophysiology
of the heart failure with preserved ejection fraction (HFpEF) is mainly due to
the myocardial microcirculatory impairment. In heart failure with reduced
ejection fraction (HFrEF) neurohumoral mechanisms affecting the peripheral
vasculature have been identified as important factors in the development and
progression of heart failure, leading to unfavourable remodelling, and thus some
of them being important treatment targets. Among many new clinical scenarios
where both myocardial and peripheral microcirculation play an important role,
raising field of implantable continuous flow assist devices opens many questions
and implies better understanding of their effects of microcirculation, as they
usually lead to the improvement of end organ dysfunction caused by previous heart
failure, which is probably through the positive effects of peripheral
microcirculation.
PMID- 29938613
TI - Vasospastic Angina and its Relationship with the Coronary Microcirculation.
AB - Vasospastic angina is an important cause of chest pain due to coronary artery
vasospasm that is related to poor quality of life and can lead to myocardial
infarction, arrhythmias and death. Since its first description as "Prinzmetal or
variant angina" which was believed to be a focal spam that occurred in non
obstructed epicardial coronary arteries, physician and researchers were gradually
confronted with the clinical reality and came to the conclusion that the coronary
artery vasospasm was considerably more polymorphic than initially described.
Although mechanism leading to vasospastic angina is not completely understood,
nowadays the medical community acknowledges that it exhibits a large variability
in clinical practice ranging from focal to diffuse epicardial vasospasm. Main
proposed mechanisms are impairment of parasympathetic activity, coronary vascular
and microvascular dysfunction due to blunted response to nitric oxide endothelium
dependent coronary vasodilatation, increased release of vasoconstricts, and
oxidative stress.
PMID- 29938614
TI - Impact of the 719Arg Variant of KIF6 and Major Cardiovascular Events on Patients
who Received Statins: A Systematic Review and Meta-Analysis.
AB - PURPOSE: The purpose of this study was to determine the relationship between
Kinesin like protein 6 (KIF6) gene Trp719Arg and major cardiovascular events
(MACEs) risk in subjects who received statin therapy. METHODS: PubMed, EmBase,
and the Cochrane Library were searched from inception through September 2017. The
selected studies evaluated the association of Trp719Arg with MACEs in individuals
who received statins. Relative risk (RR) and 95% confidence interval (CI) were
used to evaluate the effect of statin therapy on MACEs in subjects carrying
polymorphisms, and the odds ratio (OR) and 95% CI were used to evaluate the
relationship between Trp719Arg and MACE risk in individuals who received statins,
using the random-effects model. RESULTS: Seven studies were included (N=48,885).
Overall, we found that statin therapy significantly reduced the risk for MACEs in
subjects carrying ArgArg (RR: 0.79; 95% CI: 0.69-0.90; P=0.001), ArgTrp (RR:
0.71; 95% CI: 0.60 -0.83; P<0.001), ArgArg+ArgTrp (RR: 0.71; 95% CI: 0.63 -0.81;
P<0.001), and TrpTrp (RR: 0.79; 95% CI: 0.73-0.85; P<0.001). Furthermore, there
was no significant difference between subjects carrying ArgArg and those carrying
TrpTrp (OR: 1.11; 95% CI: 0.92-1.34; P=0.265). However, ArgTrp (OR: 1.29; 95% CI:
1.07-1.55; P=0.007) and ArgArg+ArgTrp (OR: 1.26; 95% CI: 1.05-1.51; P=0.012) were
associated with an increased risk for MACEs when compared with TrpTrp.
CONCLUSIONS: Statin therapy significantly reduced the risk for MACEs in subjects
carrier specific KIF6 gene Trp719Arg polymorphisms. Further, subjects carrying
ArgTrp or ArgArg+ArgTrp had a greater incidence of MACEs as compared with TrpTrp
when they received statins.
PMID- 29938615
TI - Editorial: In Silico Studies in Drug Research Against Neurodegenerative Diseases.
PMID- 29938616
TI - The Role of E-cadherin in Helicobacter pylori-Related Gastric Diseases.
AB - Helicobacter pylori (H. pylori)-related gastric diseases are a series of gastric
mucosal disorders associated with H. pylori infection, including chronic
gastritis, gastric ulcer and gastric cancer (GC) etc. The formation of GC is
widely believed to be a multistep process, evolving from gastritis and gastric
ulcer. Thus, to explore the mechanisms of gastric mucosa from benign to malignant
pathological evolution process is the crux of prevention and treatment of GC. As
an important adhesion molecule of epithelial cells, E-cadherin plays a key role
in the development of gastric diseases. In this review, we provide an overview
about the relationship of E-cadherin and H. pylori, and the role of E-cadherin in
chronic gastritis, gastric ulcer, gastric precancerous lesions and GC, aiming to
seek the characteristic of E-cadherin expression at different stages of gastric
diseases.
PMID- 29938617
TI - Role of Osmolytes and their Transporter Systems in Pathogen Survival and
Pathogenicity.
AB - BACKGROUND: Pathogenic microbes routinely keep encountering different types of
stress in their environment such as high osmolarity, high temperature, pH
fluctuations in host gut etc. They tend to acquire certain small molecular weight
molecules, termed osmolytes, so as to handle these challenges and survive in
harsh conditions. These osmolytes include some which are self-synthesized by the
microorganisms, while majority of them are imbibed from the external environment
via osmolyte transporters. METHODS: In this review, we have discussed work done
on osmolytes and their transport systems, which influence upon sustenance and
virulence of the pathogens under the given stress conditions. RESULTS: Osmolytes
and their transport systems play vital role in efficient maintenance of cell
turgidity and electrolyte levels for proper cell functioning. These molecules
don't disturb normal metabolic processes within the microbial cell at all; it
rather stabilizes the macromolecules, such as nucleic acids and proteins.
Besides, these osmolytes also empower the microbes with the pathogenicity
potential under harsh conditions such as salt, pH, temperature stress, and the
efficient host immunity. CONCLUSION: Exploring avenues with respect to osmolyte
transport systems is the need of the hour especially in this time where we are
facing the evolution of antibiotic resistance in pathogens. Most interestingly, a
detailed study of bacterial stress responses would prove to be useful in
comprehending what these pathogens face in the host microenvironment, whereby we
can manipulate the pathogen survival in human gut, and hence address the menace
of pathogenic resistance in humans as well as animals.
PMID- 29938618
TI - Beneficial Morphofunctional Changes Promoted by Sildenafil in Resistance Vessels
in the Angiotensin II-Induced Hypertension Model.
AB - BACKGROUND: By acting on multiple targets and promoting diverse actions,
angiotensin II (Ang II) plays a pivotal role in vascular function. Recent studies
suggested that phosphodiesterase-5 (PDE-5) inhibitors exhibit therapeutic effects
in cardiovascular diseases. Here, the effects of sildenafil on vascular
disturbances were analyzed in a mouse model of Ang II-induced hypertension.
METHODS AND RESULTS: Male C57BL/6 mice were used as untreated animals (control)
or infused with Ang II (1000 etag/kg/min) for 28 days and treated with sildenafil
(40 mg/kg/min) or vehicle (Ang II) during the last two weeks. After 4 weeks, the
Ang II animals exhibited a high systolic blood pressure (186+/-3 mmHg vs. 127+/-3
mmHg for control mice), which was attenuated by sildenafil (163+/-7 mmHg). The
mesenteric vessels from the Ang II animals revealed damage to the endothelial
layer, an increase in the cross-section area (1.9-fold) and vascular cell
production of peroxynitrite (512+/-13 a.u.), which was ameliorated in the Ang II
Sil group (1.2-fold and 400+/-17 a.u.). Analysis of the vascular responsiveness
showed an increased contractility response to norepinephrine in Ang II animals
(Rmax: 70%), which was abolished by sildenafil through increased nitric oxide
(NO) bioavailability and decreased reactive oxygen species (ROS) and
vasoconstrictor prostanoids. CONCLUSION: Sildenafil attenuates the
morphofunctional deleterious effects of Ang II on resistance vessels. The
benefits of sildenafil seem to occur through restoring the balance of
ROS/NO/eicosanoids. Therefore, this study opened new avenues for further clinical
targeting of the treatment of cardiovascular diseases related to activation of
the renin-angiotensin system.
PMID- 29938619
TI - A Proteomic Analysis of the Virulence Factors of Three Common Bacterial Species
Involved in Periodontitis and Consequent Possible Atherosclerosis: A Narrative
Review.
AB - The incidence of cardiovascular disorders, especially coronary artery disease and
atherosclerosis, is increasing alarmingly. Clarifying the underlying causes is of
the utmost importance and should be elucidated in order to reduce this growing
trend. Periodontitis is known as a chronic destructive disease with sophisticated
pathophysiological mechanisms that slowly impose negative effects not only on the
oral tissues but also on distant organs. Additionally, it has been shown in many
studies that atherosclerosis and periodontitis utilized common inflammatory
signaling pathways and mediators. Several lines of evidence have demonstrated the
signatures of periodontitis-related bacteria in atherosclerotic plaque specimens.
It is proposed that virulent proteins of these bacteria probably accelerate the
initiation or development of plaque formation on the inner walls of the coronary
arteries. Proteomics techniques are very sensitive and have a global point of
view. They can help to discover host factors and pathogenrelated biomarkers. This
review summarizes the studies focused on the three most important bacterial
species involved in both diseases and presents recent findings about the
proteomic evaluation of virulence factors of these bacteria. The known mechanisms
of action of the virulence factors are also described.
PMID- 29938620
TI - Diabetes in menopause: risks and management.
AB - The aim of this review is to present, critically appraise and qualitatively
synthesize current evidence on the risk of type 2 diabetes mellitus (T2DM)
development during menopause, the management of climacteric symptoms in women
with T2DM and the management of T2DM in postmenopausal women. Menopause
represents the end of reproductive life in women, as a result of ovarian aging.
It is characterized by substantial decrease in the endogenous oestrogen
concentrations and it is accompanied by alterations in body weight, adipose
tissue distribution and energy expenditure, as well as insulin secretion, insulin
sensitivity and activity that can predispose to the development of T2DM,
independently of, and additively to, aging. Many women in midlife experience
climacteric symptoms, including hot flushes and night sweats, resulting in an
indication to receive Hormone Replacement Treatment (HRT). HRT has a favourable
effect on glucose homeostasis both in women without and with T2DM. The latter was
considered in the past as a cardiovascular disease (CVD) equivalent, which would
suggest that women with the disease should not receive HRT. However, nowadays
evidence exists to support an individualized approach of women based on their CVD
risk, as some women with T2DM may be excellent candidates for HRT. Regarding T2DM
management for women in menopause, lifestyle intervention, including diet and
exercise, constitutes its cornerstone. However, most of these women will
eventually require pharmacologic therapy. The most suitable agents should be
selected according to their metabolic, cardiovascular and bone effects, taking
into consideration the specific characteristics and comorbidities of each
postmenopausal woman.
PMID- 29938621
TI - A Novel Combination of omega-3 Fatty Acids and Nano-Curcumin Modulates
Interleukin-6 Gene Expression and High Sensitivity C-reactive Protein Serum
Levels in Patients with Migraine: A Randomized Clinical Trial Study.
AB - BACKGROUND: Migraine is a disabling neuroinflammatory condition characterized by
increasing the levels of interleukin (IL)-6, a proinflammatory cytokine and C
reactive protein (CRP) which considered as a vascular inflammatory mediator,
disrupting the integrity of blood-brain barrier and contributing to neurogenic
inflammation, and disease progression. Curcumin and omega-3 fatty acids can exert
neuroprotective effects through modulation of IL-6 gene expression and CRP
levels. The aim of present study is the evaluation of combined effects of omega-3
fatty acids and nano-curcumin supplementation on IL-6 gene expression and serum
level and hs-CRP levels in migraine patients. METHODS: Eighty episodic migraine
patients enrolled in the trial and were divided into four groups as 1)
combination of omega-3 fatty acids (2500 mg) plus nano-curcumin (80 mg), 2) omega
3 (2500 mg), 3) nanocurcumin (80 mg), and 4) the control (omega-3 and nano
curcumin placebo included oral paraffin oil) over a two-month period. At the
beginning and the end of the study, the expression of IL-6 from peripheral blood
mononuclear cells and IL-6 and hs-CRP serum levels were measured, using a real
time PCR and ELISA methods, respectively. RESULTS: The results showed that both
of omega-3 and nano-curcumin down-regulated IL-6 mRAN and significantly decreased
the serum concentration. hs-CRP serum levels significantly decrease in
combination and nano-curcumin within groups (P<0.05). An additive greater
reduction of IL-6 and hs-CRP was observed in the combination group suggested a
possible synergetic relation. CONCLUSION: It seems that omega-3 fatty acids and
curcumin supplementation can be considered a new promising target in migraine
prevention.
PMID- 29938622
TI - Nutrition and Nutraceuticals in Neuroinflammatory and Brain Metabolic Stress:
Implications for Neurodegenerative Disorders.
AB - BACKGROUND AND OBJECTIVE: A steep rise in the incidences of neurodegenerative
disorders could be the combined effect of several non-genetic factors such as
increased life expectancy, environmental pollutants, lifestyle, and dietary
habits, as population-level genetic change require multiple generations. Emerging
evidence suggests that chronic over-nutrition induces brain metabolic stress and
neuroinflammation, and are individually known to promote neurodegenerative
disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and
Huntington's disease (HD). Although the association of metabolic disorders such
as diabetes, hypertension, dyslipidemia, and atherosclerosis with the dietary
habits is well known, neuronal implications of diet and nutritional factors is
still in its infancy. Transcriptomics and proteomics-based studies support the
view that nutraceuticals target multiple neuroprotective pathways in a slow but
effective manner without causing severe adverse effects, and may represent the
future of tackling neurodegenerative disorders. CONCLUSION: In this article we i)
review the diet/dietary supplement connection with brain metabolic stress and
neuroinflammation and ii) summarize current knowledge of the effects of
nutraceuticals on neurodegenerative disorders.
PMID- 29938623
TI - Quantitative Proteomics Reveals Changes in Transporter Protein Abundance in
Liver, Kidney and Brain of Mice by Pregnancy.
AB - BACKGROUND: Few studies have systematically investigated pregnancy-induced
changes in protein abundance of drug transporters in organs important for
drug/xenobiotic disposition. OBJECTIVE: The goal of this study was to compare
protein abundance of important drug/xenobiotic transporters including Abcb1a,
Abcg2, Abcc2, and Slco1b2 in the liver, kidney and brain of pregnant mice on
gestation day 15 to that of non-pregnant mice. METHODS: The mass spectrometry
based proteomics was used to quantify changes in protein abundance of
transporters in tissues from pregnant and non-pregnant mice. RESULTS: The protein
levels of hepatic Abcc2, Abcc3, and Slco1a4 per ug of total membrane proteins
were significantly decreased by pregnancy by 24%, 72%, and 70%, respectively. The
protein levels of Abcg2, Abcc2, and Slco2b1 per ug of total membrane proteins in
the kidney were significantly decreased by pregnancy by 43%, 50%, and 46%,
respectively. After scaling to the whole liver with consideration of increase in
liver weight in pregnant mice, the protein abundance of Abcb1a, Abcg2, Abcc2,
Abcb11, Abcc4, Slco1a1, and Slco1b2 in the liver was ~50-100% higher in pregnant
mice, while those of Abcc3 and Slco1a4 were ~40% lower. After scaling to the
whole kidney, none of the transporters examined were significantly changed by
pregnancy. Only Abcg2 and Abcb1a were quantifiable in the brain and their
abundance in the brain was not influenced by pregnancy. CONCLUSION: Protein
abundance of drug transporters can be significantly changed particularly in the
liver by pregnancy. These results will be helpful to understand pregnancy-induced
changes in drug/xenobiotic disposition in the mouse model.
PMID- 29938624
TI - Interfacial Phenomenon Based Biocompatible Alginate-Chitosan Nanoparticles
Containing Isoniazid and Pyrazinamide.
AB - BACKGROUND: Tuberculosis (TB) is one of the major health challenge in the world.
The current treatment of TB needs daily administration of combined drug therapy
for six or more months. Sometime non-adherence and less bioavailability from
current therapy develops multidrug resistance, as a result, high dose requirement
and subsequent intolerable toxicity are seen. Therefore, nanotechnology gained
special attention as it has potential to improve patient compliance,
bioavailability and reduction in dosing frequency. OBJECTIVE: The aim of this
study is to fabricate alginate-chitosan nanoparticles (AL-CS NPs) under
appropriate conditions using ionic gelation method. The use of natural polymers
in nanoparticle fabrication has a vast application due to their biodegradability,
biocompatibility and nontoxic nature. Ionic gelation method involves the
interaction between macromolecules with opposite charged ionizable groups forming
polyelectrolyte complex. Hence, it is rational to formulate natural polymerbased
sustained release nano-particulate matrix to improve patient adherence, reducing
dose frequency and drug toxicity. METHOD: The formulations were based on 32
factorial designs. Nanoparticles of combined drug (Isoniazid- INH and
Pyrazinamide-PYZ) were fabricated using natural polymer. Formulation process
involved the use of pregelated sodium alginate by ionic gelation method.
Pregelation of sodium alginate included calcium chloride. The effects of sodium
alginate concentration and chitosan concentration on particle size, zeta
potential, entrapment efficiency and in vitro drug release were studied. RESULTS:
Optimized Batch-3s showed particle size 539.7 +/- 2.33 nm, zeta potential -26.4
+/- 0.55 mV, and entrapment efficiency is 70.21 +/- 0.24 % and 73.45 +/- 0.21% of
INH and PYZ respectively. Dissolution release study of Batch-3s in 7.4 pH
phosphate buffer exhibited the initial burst of 5.04+/-0.45 % and19.68 +/-
0.87 % at 0.25 hrs followed by slow, sustained release of drug 74.53 +/-
2.53and 57.87 +/- 2.04 % at 10 hrs of INH and PYZ, respectively. CONCLUSION: It
concluded that chitosan (CS) and sodium alginate (AL) concentration are rate
limiting factors in formulation development. Natural polymer based combined drug
nano-particulate system could be an innovative and optimistic approach in the
treatment of TB.
PMID- 29938625
TI - Gullibility may be a warning sign of Alzheimer's disease dementia.
AB - : ABSTRACTBackground:Theory of Mind reasoning, which plays a pivotal role in
social interaction, is required to detect deception. Empirically, those with
cognitive decline are vulnerable to deception. METHODS: Participants were 45
healthy elderly adults with clinical dementia rating (CDR) 0, and 76 outpatients:
25 with amnestic mild cognitive impairment (aMCI, CDR 0.5), 34 with mild
Alzheimer's disease dementia (ADD, CDR 1), and 17 with moderate ADD (CDR 2). The
task consisted of two single-frame cartoons that depicted a character with an
intention to deceive another character using social signs of gaze and pointing,
and participants are provided clue questions to detect the character's
intentions. RESULTS: The percentage of participants who detected the character's
intention decreased with ADD progression (CDR 0, 82.2%; CDR 0.5, 48.0%; CDR 1,
29.4%; and CDR 2, 0%). Total score (0-6) also decreased with ADD progression (CDR
0, 4.4 +/-1.1; CDR 0.5, 3.0 +/-1.3; CDR 1, 2.9 +/-1.5; and CDR 2, 1.6 +/-0.9).
DISCUSSION AND CONCLUSIONS: The present study demonstrated that those with aMCI
have difficulty in detecting other's deceiving intentions, when the intention was
shown implicitly using social signs. In a previous study, we have reported that
mild ADD showed difficulties in detecting intention, while aMCI succeeded in
detection when the intention was depicted explicitly. These results together
suggested that those with aMCI is vulnerable to deception when the intention was
shown implicitly using non-verbal cues, while ADD may fail to detect the
intention even when the intention was shown explicitly.
PMID- 29938626
TI - An Experimental Investigation into the Effect of State-Anxiety on State-Paranoia
in People Experiencing Psychosis.
AB - BACKGROUND: There is strong evidence to suggest that anxiety is associated with
paranoia in clinical and non-clinical samples. However, no research to date has
directly manipulated anxiety to investigate if state-anxiety has a causal role in
state-paranoia in clinical populations. AIMS: To investigate whether an anxious
mood induction leads to greater paranoia than a neutral-mood induction in people
experiencing psychosis and paranoia and, if so, whether this is predicted by
anxiety over and above other variables. METHOD: 22 participants with a psychosis
spectrum diagnosis took part in a two condition cross-over experimental design.
Participants underwent a neutral-mood and an anxious-mood induction with levels
of state-anxiety, state-affect and state-paranoia being measured before and after
each condition. RESULTS: State-paranoia was significantly higher after the
anxious condition compared with the neutral condition. State-anxiety and negative
affect were significant predictors of levels of state-paranoia after the anxious
condition. When both predictors were included in a regression model, only
negative-affect was a significant predictor of state-paranoia after the anxious
condition. There were a number of methodological limitations. CONCLUSIONS: State
anxiety and negative-affect may both be involved in the maintenance of paranoia
in clinical populations, as predicted by cognitive models. Negative-affect may be
the strongest predictor of state-paranoia in clinical populations. Reasons for
this are discussed, as well as the implications. Interventions that seek to
reduce negative state-affect may be beneficial in managing state-paranoia.
Further research is warranted to explore the suggested clinical and theoretical
implications of these findings.
PMID- 29938627
TI - Conceptual Models of Early and Involuntary Retirement among Canadian Registered
Nurses and Allied Health Professionals.
AB - : ABSTRACTAvailability of health professionals is fundamental to population
health. Multiple trends contribute to provider shortages. PURPOSE: Develop and
validate conceptual models of early and involuntary retirement among registered
nurses (RNs) and allied health professionals (AHPs). METHOD: A review of
retirement literature (n = 23 studies). Any factor reported as predictive of
early or involuntary retirement was incorporated into a model. To achieve face
validity, we conducted interviews with Canadian RNs/AHPs (n = 14). RESULTS: The
conceptual model of early retirement had eight categories (38 variables):
workplace characteristics, socio-demographics, attitudes/beliefs, broader
context, organizational factors, family, lifestyle/health, and work-related. The
model of involuntary retirement had four categories (eight variables): broader
context, socio-demographics, lifestyle/health, and family. Caregiving
responsibilities (variable) was added based on interview data. DISCUSSION:
RNs/AHPs consider many factors when contemplating retirement; some are sensitive
to intercession, which generates possibilities for extending the work lives of
older RNs and AHPs.
PMID- 29938628
TI - Nosocomial impact of prevalent beta-lactamases from the community
enterobacteriaceae: what to do when the resistance doesn't go your way.
PMID- 29938629
TI - [A family with a congenital DICER1 mutation].
AB - Germ line DICER1 mutations predispose to a syndrome associated with increased
risk of e.g. multinodular goitre (MNG), pleuropulmonary blastoma and Sertoli
Leydig cell tumour (SLCT). This is a case report about a family with a nonsense
DICER1 mutation, c.988C>T, affecting six family members. The proband had once
undergone a unilateral oophorectomy and a thyroidectomy due to SLCT and MNG,
respectively. The proband has two children with the mutation but with no
manifestations. Given this circumstance, we discuss the prospects of an
implementation of screening programmes for children with predisposed cancerous
syndromes.
PMID- 29938630
TI - [Asbestosis and pleural plaques].
AB - Asbestos was used in numerous products until its total ban in Denmark in 1988.
The prevalence of asbestosis and pleural plaques does not yet appear to be
falling. Unfortunately the statistics are unreliable due to errors in the Danish
translation of the ICD-10 codes of the disease. In this review, clinical and
radiologic diagnostic criteria of asbestosis and pleural plaques and
recommendations for follow-up of patients are described. Typical changes on a
high-resolution CT scan combined with relevant asbestos exposure is essential for
the diagnosis. Asbestosis and pleural plaques are both notifiable in Denmark.
PMID- 29938631
TI - [Surgical treatment for lymphoedema].
AB - Lymphoedema is a frequent condition after surgical treatment for breast cancer.
Lymphoedema causes great discomfort for the patients and is primarily treated
conservatively with compression garments and physical therapy. Recently, surgical
interventions have gained popularity in the form of lympho-lymphatic anastomoses,
lympho-venous anastomoses and autologous lymph node transplantation, either as
stand-alone treatment or in combination with secondary breast reconstruction. In
Denmark, lympho-venous anastomoses is currently the primary surgical treatment
for lymphoedema.
PMID- 29938632
TI - [Intersection syndrome in a tetraplegic hand cyclist].
AB - Wrist tendinopathies are common overuse injuries in athletes and often associated
with activities such as rowing, riding or racket sports. Correctly diagnosing the
various tendinopathies is essential for management of cases refractory to initial
treatment. Easily mistaken for de Quervain's tenosynovitis, the intersection
syndrome may be effectively managed by simple taping negating the need for
corticosteroid injection and tendon release surgery. We present an unusual case
report of intersection syndrome in a tetraplegic hand cyclist following a 24-hour
endurance race.
PMID- 29938633
TI - [Treatment of stable chronic obstructive pulmonary disease].
AB - In 2012, The Danish Society of Respiratory Medicine gave birth to their most
recent guideline regarding chronic obstructive pulmonary disease (COPD). Much has
happened since, and in late 2017 an update has been published. Chapters have been
deleted, and new ones added. The major alteration has been in the section
concerning treatment with inhalation medication - now aiming at an easy stepwise
up-titration of long-acting medicine as well as a guide of how to down-titrate
inhaled corticosteroids. This review mainly focuses on how to treat stable COPD
according to The Danish Society of Respiratory Medicine.
PMID- 29938635
TI - ?
PMID- 29938634
TI - [Rectal carcinoma in a 24-year-old man with Hirschsprung's disease].
AB - This case report presents an incident of rectal carcinoma in a 24-year-old man
with Hirschsprung's disease, for which he was operated in his early childhood,
with a Soave pull-through procedure. No direct association between Hirschsprung's
disease and rectal cancer was found in our review of the literature. However,
several case reports of rectal cancers following pull-through procedures exist. A
low threshold for further clinical investigations is recommended, if these
patients are presenting with gastrointestinal symptoms.
PMID- 29938636
TI - ?
PMID- 29938637
TI - ?
PMID- 29938638
TI - [Death criteria - now and in the future].
AB - Death can be pronounced on both circulatory and brain criteria. In both cases,
irreversible loss of brain function is essential in understanding finale death,
as irreversible loss of breathing - a brainstem function - is mandatory. Brain
function ceases irreversibly as a consequence of lack of blood supply to the
brain, caused by circulatory arrest or by raised intracranial pressure. Brain
function is central in death, which must be reflected in a future death
criterion, stated in WHO's new death criterion based on irreversible loss of
capacity for consciousness and loss of brainstem function.
PMID- 29938639
TI - [Treating scars with lipofilling].
AB - Hypertrophic, keloidal and contracted scars can be cosmetically and functionally
debilitating, and by patients this is often perceived as traumatising.
Psychological and social impairments are common in these types of scars.
Currently, autologous lipofilling, with or without enrichment with stem cells, is
performed to improve scar quality. In this review, we evaluate the evidence on
lipofilling as a treatment of scars. The literature mainly consists of studies of
low-level evidence, i.e. they lack controls and randomisation. Nevertheless, all
studies indicate, that lipofilling may improve the quality of scars.
PMID- 29938640
TI - [Rickets and anaemia caused by coeliac disease in a three-year-old girl].
AB - We present a case report of a three-year-old girl of Pakistani origin with
coeliac disease. The first symptom was spontaneous fracture of the fibula.
Vitamin D deficiency rickets and iron deficiency anaemia were demonstrated. An
intestinal biopsy and elevated antibody levels confirmed the coeliac disease.
Rickets is a known but rare presentation of coeliac disease, but this case report
illustrates, how coeliac disease in children often presents with non
gastrointestinal symptoms. The importance of investigations for malabsorp-tion,
if iron deficiency is not easily corrected with sufficient iron supplements, is
underlined as well as the importance of screening for coeliac disease.
PMID- 29938641
TI - [Danish public research investments in clinical trials].
AB - Clinical trials are important to ensure that patients and society benefit from
healthcare interventions. Among the Danish public research investments in medical
sciences the main part of funding is given to preclinical and translational
research, and less than ten per cent is given to clinical trials. This imbalance
may have negative consequences for patients and society, because public
investment in clinical trials is likely to ensure broader availability of tested
interventions independent of diseases, patient groups, caregivers and clinical
settings.
PMID- 29938642
TI - [Transorbital penetrating injury without sequlae].
AB - A 33-year-old man was admitted to hospital with a butter knife stuck in his head
after having attempted to commit suicide by forcing the knife through his skull.
Physical examination revealed a stable patient with only minimal associated
haemorrhage. A CT scan revealed, that the penetrating knife had passed through
the sphenoid bone, the posterior orbit and the ethmoid cells and ended in the
contralateral nasal cavity. The knife was removed by its own trajectory. After
surgery, the patient was neurologically intact with normal sight and well
functioning eye movements, and he made a full recovery.
PMID- 29938643
TI - [Reduced risk of diabetes and cardiovascular disease after bariatric surgery].
AB - The worldwide incidence of obesity, defined as a BMI >= 30 kg/m2, has more than
doubled during the past four decades. Bariatric/metabolic surgery provides the
largest and most sustainable degree of weight loss. This review briefly
summarises the emerging randomised evidence of the superiority of these
procedures over conventional treatment, in achieving glycaemic control and
inducing remission in patients with type 2 diabetes as well as the observational
evidence suggesting improvements in the long-term risks of cardiovascular
outcomes and mortality.
PMID- 29938644
TI - [Return to play after anterior cruciate ligament reconstruction].
AB - After anterior cruciate ligament (ACL) reconstruction, 30% of the patients aged
20 years and younger experience a second injury. Studies imply, that with the
right rehabilitation and testing many of these injuries can be prevented. Return
to play should not be allowed until nine months after surgery at the earliest and
should be based on relevant testing of strength, function and mental readiness.
PMID- 29938645
TI - [Two immigrant children with vitamin D poisoning].
AB - The Danish National Board of Health recommends vitamin D supplement for children
under two years, regardless of race or nutrition source. Danish studies have
found, that 50-80% of children of Palestinian and Pakistani origin of the ages 0
16 years had vitamin D deficiency. This case report of vitamin D poisoning in two
immigrant children shows, that there is a group of people, who are not aware of
the correct dosage. Doctors as well as healthcare practitioners should be aware
of the problem.
PMID- 29938646
TI - [Schizophrenia is a clinically and biologically heterogeneous syndrome].
AB - Currently psychiatric diagnoses are solely based on clinical psychopathological
criteria, and do not involve objective biological markers. However, a wealth of
neuropsychiatric research supports, that schizophrenia is both clinically and
biologically a heterogeneous syndrome. Perspectives for neurobiological
subgrouping of patients with schizophrenia, targeted treatment regimens as well
as clarification of early causal risk factors envision, that in the coming years
objective neuropsychiatric paradigms will be implemented in clinical practice.
PMID- 29938648
TI - Editorial.
PMID- 29938649
TI - Chinese calligraphic writing to enhance cognitive performance and emotional
calmness in older adults with mild cognitive impairment.
PMID- 29938647
TI - Histone H3 threonine 11 phosphorylation by Sch9 and CK2 regulates chronological
lifespan by controlling the nutritional stress response.
AB - Upon nutritional stress, the metabolic status of cells is changed by nutrient
signaling pathways to ensure survival. Altered metabolism by nutrient signaling
pathways has been suggested to influence cellular lifespan. However, it remains
unclear how chromatin regulation is involved in this process. Here, we found that
histone H3 threonine 11 phosphorylation (H3pT11) functions as a marker for
nutritional stress and aging. Sch9 and CK2 kinases cooperatively regulate H3pT11
under stress conditions. Importantly, H3pT11 defective mutants prolonged
chronological lifespan (CLS) by altering nutritional stress responses. Thus, the
phosphorylation of H3T11 by Sch9 and CK2 links a nutritional stress response to
chromatin in the regulation of CLS.
PMID- 29938650
TI - Brief integrated sleep-focused treatment for persistent sleep disturbance in
residual depression: an assessor-blind, parallel group, randomised controlled
study.
PMID- 29938651
TI - Effect of health empowerment intervention for stroke self-management on behaviour
and health in stroke rehabilitation patients.
PMID- 29938652
TI - Chronic disease self-management and cognitive training programme to improve
diabetic control in older outpatients with memory complaints: a randomised trial.
PMID- 29938653
TI - Adoption of the reference framework for diabetes care by primary care physicians.
PMID- 29938654
TI - Improving early risk stratification in patients presenting to emergency
department with suspected acute coronary syndrome.
PMID- 29938655
TI - Assessment of long-term functional outcome in patients who sustained moderate or
major trauma: a 4-year prospective cohort study.
PMID- 29938656
TI - Home-based interactive e-health educational intervention for middle-aged adults
to improve total exercise, adherence rate, exercise efficacy, and outcome: a
randomised controlled trial.
PMID- 29938657
TI - Perceived unmet supportive care needs and determinants of quality of life among
survivors of head and neck cancer.
PMID- 29938658
TI - Voice performance in tonal language speakers with glottal insufficiency due to
unilateral vocal fold paralysis after injection laryngoplasty: a multidimensional
study of Cantonese patients.
PMID- 29938659
TI - Effectiveness of a multidisciplinary approach to geriatric hip fractures in
improving clinical outcomes and cost of care.
PMID- 29938660
TI - Hong Kong domestic health spending: financial years 1989/90 to 2013/14.
PMID- 29938661
TI - Editorial.
PMID- 29938662
TI - Prevalence and characteristics of hardcore smokers in Hong Kong.
PMID- 29938663
TI - A brief, tailored smoking cessation intervention for smokers with diabetes
mellitus in Hong Kong.
PMID- 29938664
TI - Auditory-based cognitive training programme for attention and memory in older
people at risk of progressive cognitive decline: a randomised controlled trial.
PMID- 29938665
TI - Transcranial Doppler ultrasonography for detection of cerebral white matter
changes in a high-risk population.
PMID- 29938666
TI - Association of wheeze during the first 18 months of life with indoor nitrogen
dioxide, formaldehyde, and family history of asthma: a prospective cohort study.
PMID- 29938667
TI - Long-term efficacy of an education programme in improving adherence with
continuous positive airway pressure treatment for obstructive sleep apnoea.
PMID- 29938668
TI - Electroacupuncture and wrist splinting for carpal tunnel syndrome: a randomised
trial.
PMID- 29938669
TI - Bipolar transurethral vapourisation versus monopolar transurethral resection of
prostate: a randomised controlled trial.
PMID- 29938670
TI - Effect of weight reduction on severity of lower urinary tract symptoms in obese
men with benign prostatic hyperplasia.
PMID- 29938671
TI - Quality of life and symptom measurement in Chinese women with pelvic floor
disorders: validation study of Pelvic Floor Distress Inventory and Pelvic Floor
Impact Questionnaire.
PMID- 29938672
TI - Pelvic floor disorders related to pregnancy: a prospective observational study.
PMID- 29938673
TI - Bone marrow mesenchymal stem cells modified pathological changes and
immunological responses in ovalbumin-induced asthmatic rats possibly by the
modulation of miRNA155 and miRNA133.
AB - In the current experiment, we investigated the immune-modulatory potential of
mesenchymal stem cells (MSCs) and conditioned media (CM) in attenuating of
chronic asthmatic changes in a rat model. Male rats were divided into control (C)
and ovalbumin-sensitized (S) groups, which further allocated into three
subgroups; rats received systemically 50 MUl volume of PBS (C and S groups), CM
(CSV and SSV groups) and rats received intravenous infusion of 2 * 106 bone
marrow-derived mesenchymal stem cells (rBMMSCs) (CCV and SCV groups). Two weeks
later, the expression of interleukin (IL)-4, IL-13, and IL-10, miRNA133, and
miRNA155 was measured by real-time PCR. Pathological changes and the recruitment
of rBMMSCs into pulmonary parenchyma were evaluated by histopathological and
immunofluorescence analyses, respectively. The systemic injection of rBMMSCs, but
not CM, decreased the levels of IL-4, IL-13, IL-10, miRNA133, miRNA155 and
reduced pathological changes in sensitized rats as compared with other sensitized
groups (p < 0.001 to p < 0.05). rBMMSCs transmigrated to lung tissue in cell
administrated rats, albeit intensity of asthmatic changes, in turn, affected the
amount of recruited cells. Collectively, our data suggest the potential role of
MSCs, but not CM, in reducing pathological changes possibly via the modulation of
miRNA133 and miRNA155 during asthmatic changes.
PMID- 29938674
TI - Analysis of Fos expression in the rat olfactory neurogenic region following
single exposure to maternal separation during different neonatal stages.
AB - Accumulating evidence confirms that the exposure of neonatal rats to maternal
separation can significantly alter individual processes of postnatal neurogenesis
in the olfactory neurogenic region - the subventricular zone (SVZ) and the
rostral migratory stream (RMS). To establish the stressful influence of MS on
postnatal neurogenesis we have investigated whether altered olfactory environment
caused by short-term MS induces expression of Fos protein in the SVZ/RMS and in
the olfactory cortical area - anterior olfactory nucleus (AON) of neonatal rats.
Pups were separated from mothers for 2 hours at the postnatal days 7, 14 and 21.
Immunohistochemically labeled Fos protein was assessed. Our results revealed that
single exposure to MS is a stressful event that selectively and in age-dependent
manner stimulates cellular activity in the SVZ and AON. A few Fos+ cells were
found in the SVZ of P21 control animals and MS significantly increased their
number. This suggests that some SVZ cells are included in the circuitry, which is
activated by MS and that these cells have complete equipment for the Fos signal
transduction. MS significantly increased the number of Fos+ cells in the AON in
all age stages examined suggesting that its effect is mediated by olfaction.
PMID- 29938675
TI - Comparison of training and detraining on redox state of rats: gender specific
differences.
AB - Given the fact that oxidative stress response induced by training/detraining has
still not been clarified and may be influenced by gender, the aim of our
investigation was to compare the effects of swimming training and detraining on
oxidative and antioxidative parameters in rats, with a special focus on sex
differences. Wistar albino rats (n = 64) were divided into 4 groups: control,
trained group, groups exposed to 2 and 4 weeks of detraining. Each group included
two subgroups: males and females. After sacrificing, hearts were isolated and
retrogradely perfused according to Langendorff technique. Levels of superoxide
anion radical, hydrogen peroxide, nitrites and thiobarbituric acid reactive
substances were measured in plasma and coronary venous effluent, while reduced
glutathione, activities of superoxide dismutase and catalase were measured in
erythrocytes. Our results indicate that swimming training doesn't promote
oxidative damage, nor act protectively within the heart. However, 2 and 4 weeks
of detraining led to a partial lost in exercise-induced adaptation. It seems that
moderate-intensity physical exercise of sufficient duration leads to beneficial
adaptations, which may be partially lost during detraining period. Positive
antioxidative effects of training remained longer in males. Findings of present
study may help in elucidation of training and detraining effects on modulation of
redox homeostasis, especially from aspect of gender differences.
PMID- 29938676
TI - Exercise training increased gene expression of LDL-R and PCSK9 in intestine: link
to transintestinal cholesterol excretion.
AB - Transintestinal cholesterol excretion (TICE) is known as an alternate non-biliary
route of cholesterol excretion from the body. The aim of this study was to
determine whether exercise training has effects on intestinal membrane receptors
involved in TICE in intact and ovariectomized (Ovx) rats. Sprague-Dawley rats
were first divided into 4 groups: Sham operated and Ovx rats fed a standard diet
(Sham-SD; Ovx-SD), or a high cholesterol diet (Sham-Chol; Ovx-Chol). These 4
groups were subsequently subdivided into either sedentary or voluntary wheel
running groups for 6 weeks. The cholesterol diet resulted in increased hepatic
cholesterol accumulation (p< 0.001) in both Sham and Ovx rats. Exercise training
increased (p < 0.01) transcripts of intestinal low density lipoprotein receptor
(LDL-R) and proprotein convertase subtilisin/kexin type 9 (PCSK9), which are
involved in trans-intestinal cholesterol uptake from circulation, in both Sham
and Ovx rats compared to rats remaining sedentary in all diet conditions. The up
regulation of intestinal gene expression of LDL-R and PCSK9 following voluntary
wheel running in intact and Ovx rats suggests that exercise training may
contribute to elimination of cholesterol through the TICE pathway.
PMID- 29938677
TI - The effect of ellagic acid on photodynamic therapy in leukemia cells.
AB - Ellagic acid (EA) is a naturally phenolic acid presented in different foods. It
has a variety of biological activities including antioxidant, anti-inflammatory,
anti-microbiological and anti-cancer properties. On account of its antioxidant
activity, EA might protect cancer cells from free radical damage in photodynamic
therapy (PDT) during which reactive oxygen species (ROS) production was
stimulated leading to irreversible tumor cell injury. In this study, the
influence of EA on K562 cells in 5-aminolevulinic acid (ALA)-based PDT is
demonstrated. Cell apoptosis was assayed by flow cytometry. Oxidative damage
induced by PDT was investigated by measurement of malondialdehyde (MDA). Comet
assay was used to evaluate the potential genotoxic effect induced by PDT on the
cells. The results showed that EA supplementation alone did not affect the lipid
peroxidation, DNA damage and apoptosis in K562 cells. It increases the lipid
peroxidation, DNA damage, apoptosis and decreases the survival rate in K562 cells
induced by ALA-PDT. The singlet oxygen quencher sodium azide suppresses
apoptosis, lipid peroxidation and DNA damage induced by EA in PDT. In conclusion,
EA consumption during PDT did not decrease the effectiveness of cancer therapy on
malignant cells. The effect of antioxidants on PDT maybe was determined by its
sensitization ability to singlet oxygen.
PMID- 29938678
TI - The effect of curcumin and PI3K/Akt inhibitor on monosodium glutamate-induced rat
thymocytes toxicity.
AB - Monosodium glutamate (MSG), the sodium salt of glutamic acid, is widely used in
modern nutrition as flavor enhancer. However, it has been shown that curcumin has
ability to induce apoptosis in the cells of the immune system. In the present
study, we evaluate the potential protective effects of curcumin in MSG-induced
apoptosis and signaling pathway which may be involved. Rat thymocytes were
treated with increased (1, 10, 50 mM) MSG concentrations and/or curcumin (3 MUM).
Cell apoptosis rate, reactive oxygen species (ROS) production, mitochondrial
membrane potential (MMP), Bcl-2, Bax protein expression and caspase-3 activity
were determined after 24 hours of incubation. Treatment with MSG resulted with
increased apoptosis, ROS production and caspase-3 activity, followed with
decreased MMP and Bcl-2/Bax protein ratio. Inhibition of caspase-3 and caspase-9
activity reduced cell apoptosis, indicating the involvement of mitochondrial
apoptotic pathway. Co-treatment with curcumin markedly reduced apoptosis and ROS
production, together with increased MMP and Bcl2/Bax protein ratio. Inhibition of
PI3K/Akt signaling pathway abolished protective effect of curcumin in MSG-induced
toxicity in rat thymocytes. Obtained findings suggest that curcumin may attenuate
the MSG-induced apoptosis through PI3K/Akt signaling pathway which could be
useful in preventing the potential deficiencies in T cell-mediated immunity.
PMID- 29938679
TI - Antitussive activity of alcoxyphenyl carbamic acid analogues.
AB - In this study we report pharmacological evaluation of four newly synthetized
analogues of alcoxyphenyl carbamic acid, structurally related to butamirate
citrate that is frequently used as cough suppressing drug, and marked as ATK 231,
ATK 241, ATK 251 and ATK 261. These agents with various modifications of the
molecular structure have been tested for antitussive activity in cough induced by
inhalation of aerosol of citric acid (0.3 M) over 3 minutes using conscious
guinea pigs. Results revealed significant cough suppressing activity without
significant influence on specific airways resistances in all tested substances.
ATK 231 and ATK241 showed significantly higher total antitussive activities when
compared to both codeine phosphate and butamirate citrate, while ATK 251 only
comparing to butamirate citrate. We did not observe any notable adverse effects
and these compounds could thus potentially represent promising new non-narcotic
antitussives suitable for further studies.
PMID- 29938680
TI - Acute sleep deprivation induces cardioprotection against ischemia/ reperfusion
injury through reducing inflammatory responses: the role of central GABA-A
receptors.
AB - Sleep is considered as a physiological regulator in the body. Gamma-aminobutyric
acid (GABA) is a neurotransmitter that modulates sleep and affects cardiac
functions. We evaluated effects of acute sleep deprivation (SD) on cardiac
hemodynamic parameters, expression of pro-inflammatory cytokines, and Heat shock
protein (Hsp70), serum level of lactate dehydrogenase (LDH) and
prooxidant/antioxidant balance (PAB). Male Wistar rats were bilaterally
cannulated in the central nucleus of amygdala (CeA) and saline or bicuculline was
injected 24 hours prior to induction of 30 minute ischemia following 120 minute
reperfusion. Forty-eight animals were randomly divided into four groups: Control
(CONT), bicuculline (BIC), acute SD and bicuculline + acute sleep deprivation
(BIC+SD). Animals in SD and BIC+SD groups were put in an aquarium for inducing
sleep deprivation. SD attenuated LDH, pro-inflammatory cytokines and PAB;
improved cardiac hemodynamic parameters and increased Hsp70 in non-infarcted area
as compared to CONT. Administration of bicuculline increased LDH, pro
inflammatory cytokines and PAB, reduced cardiac hemodynamic parameters and Hsp70
as compared to CONT. Furthermore, bicuculline administration prior to acute sleep
induction decreased SD effects on LDH, PAB, Hsp70, cardiac hemodynamic parameters
and pro-inflammatory cytokines. Induction of SD prior to ischemia/reperfusion
induces cardioprotection through suppressing inflammatory responses.
PMID- 29938681
TI - Overexpression of the ABCB1 drug transporter in acute myeloid leukemia cells is
associated with downregulation of latrophilin-1.
AB - Finding new markers with appropriate prognostic levels for the differential
diagnosis of neoplastic diseases represents an important issue for biomedical
research. Recently, latrophilin-1 (LPHN1) was reported to be expressed in human
monocytic leukemia cell lines and in primary human acute myeloid leukemia (AML)
cells. However, this expression was found to be absent in healthy leukocytes.
LPHN1 was therefore considered a novel biomarker of human AML. In previous
papers, we established two P-gp-positive variants (SKM-1/VCR and MOLM-13/VCR) of
AML cell lines derived from parental human AML cells SKM-1 and MOLM-13 by
selection with VCR. The present paper addresses the measurement of LPHN1
expression in SKM-1 and MOLM-13 cells and their P-gp-positive variants. Both
parental AML lines were positive for LPHN1 expression at the mRNA and protein
levels. However, the expression of LPHN1 at both the mRNA and protein levels was
reduced in both P-gp-positive SKM-1/VCR and MOLM-13/VCR variants of AML cells.
Interestingly, we observed an elevation of the latrophilin-3 transcript in P-gp
positive variants of AML cell lines. The combined results suggest that
alterations in latrophilin expression occur in AML cells expressing P-gp.
PMID- 29938682
TI - Links between brain cortical regions and EEG recording sites derived from forward
modelling.
AB - Electroencephalography (EEG) provides no direct link between electrode positions
and underlying signal generators. Inferences based on spatial proximity between
scalp positions and cortical structures are not reliable. More accurate source
localization is obtained by solving both the forward and the inverse problem, but
is technically challenging. In this paper, we provide a reference table of
correspondence between EEG sensors and cortical anatomical regions based on a
realistic head model. We also present a universal algorithm to compute the
solution by using a forward model to determine the sensitivity for electrodes of
any defined electrode positioning system and cortical anatomical parcellation.
PMID- 29938683
TI - An in silico performance characterization of respiratory motion guided 4DCT for
high-quality low-dose lung cancer imaging.
AB - This work aims to characterize the performance of an improved 4DCT technique
aiming to overcome irregular breathing-related image artifacts. To address this,
we have developed respiratory motion guided (RMG) 4DCT, which uses real-time
breathing motion analysis to prospectively gate scans based on detection of
irregular breathing. This is the first investigation of RMG-4DCT using a real
time software prototype, testing the hypothesis that it can reduce breathing
irregularities during imaging, reduce image oversampling and improve image
quality compared to a 'conventional' 4DCT protocol without breathing guidance.
RMG-4DCT scans were simulated based on 100+ hours of breathing motion acquired
for 20 lung cancer patients. Scan performance was quantified in terms of the beam
on time (a surrogate for imaging dose), total scan time and the breathing
irregularity during imaging (via RMSE of the breathing motion during
acquisition). A conventional 4DCT protocol was also implemented using the same
software prototype for a direct comparator to the RMG-4DCT results. We
investigated the impact of key RMG-4DCT parameters such as gating tolerance,
gantry rotation time and the use of baseline drift correction. Using a
representative set of algorithm parameters, RMG-4DCT achieved significant mean
reductions in estimated imaging dose (-17.8%, p < 0.001) and breathing RMSE
during imaging (-12.6%, p < 0.001) compared to conventional 4DCT. These
improvements came with increased scan times, roughly doubled on average (104%, p
< 0.001). Image quality simulations were performed using the deformable digital
XCAT phantom, with image quality quantified based on the normalized cross
correlation (NCC) between axial slices. RMG-4DCT demonstrated qualitative image
quality improvements for three out of 10 phase bins, however the improvement was
not significant across all 10 phases (p = 0.08) at a population level. In
choosing RMG-4DCT scan parameters, the trade-off between gating sensitivity and
scan time may be optimized, demonstrating potential for RMG-4DCT as a viable
pathway to improve clinical 4DCT imaging.
PMID- 29938684
TI - Performance evaluation of the MOLECUBES beta-CUBE-a high spatial resolution and
high sensitivity small animal PET scanner utilizing monolithic LYSO scintillation
detectors.
AB - The MOLECUBES beta-CUBE scanner is the newest amongst commercially available
preclinical PET scanners for dedicated small animal imaging. The scanner is
compact, lightweight and utilizes a small footprint to facilitate bench-top
imaging. It can be used individually, or in combination with the X-CUBE CT
scanner, which provides the ability to perform all necessary PET data corrections
and provide fully quantitative PET images. The PET detector comprises of an 8 mm
thick monolithic LYSO scintillator read-out by an array of 3 mm * 3 mm
Hamamatsu silicon photomultipliers. The monolithic scintillator provides the
ability to measure depth-of-interaction which aids in the development of such a
compact scanner. With a scanner diameter of 7.6 cm and axial length of 13 cm it
is suitable for imaging both whole-body mice and rats. This paper presents the
design and imaging performance of the beta-CUBE scanner. NEMA NU4-2008
characterization and a variety of phantom and animal imaging studies to
demonstrate the quantitative imaging performance of the PET scanner are
presented. Spatial resolution of 1 mm is measured with a filtered-back projection
reconstruction algorithm at the center of the scanner and DOI measurement helps
maintain the excellent spatial resolution over the entire imaging FOV. An
absolute peak sensitivity of 12.4% is measured with a 255-765 keV energy window.
The scanner demonstrates good count-rate performance, with a peak NEC of 300 kcps
and 160 kcps measured with ~900 uCi in the NEMA mouse and rat phantoms,
respectively. Imaging data with the NEMA image quality phantom and Micro Derenzo
phantoms demonstrate the ability to achieve good image quality and accurate
quantitative data. Image uniformity of 7.4% and spill-over ratio of 8% were
measured. The superior spatial resolution, excellent energy resolution and
sensitivity also provide superior contrast recovery, with ~70% recovery for the 2
mm rods. While current commercial preclinical PET scanners have spatial
resolution in the 1-2 mm range, the 1 mm3 volumetric resolution presents
significant improvement over current commercially available preclinical PET
scanners. In combination with the X-CUBE scanner it provides the ability to
perform fully quantitative imaging with spatially co-registered high-resolution
3D PET-CT images.
PMID- 29938685
TI - ReAsH/tetracystein-based correlative light-electron microscopy for HIV-1 imaging
during the early stages of infection.
AB - Visualization of viruses in the host cell during the course of infection by
correlative light-electron microscopy (CLEM) requires a specific labelling of the
viral structures in order to recognize the nanometric viral cores in the
intracellular environment. For Human immunodeficiency virus type 1 (HIV-1), the
labelling approaches developed for fluorescence microscopy are generally not
suited for transmission electron microscopy (TEM), so that imaging of HIV-1
particles in infected cells by CLEM is not straightforward. Herein, we adapt the
labeling approach with a tetracystein tag (TC) and a biarsenical resorufin-based
label (ReAsH) for monitoring the HIV-1 particles during the early stages of HIV-1
infection by CLEM. In this approach, the ReAsH fluorophore triggers the photo
conversion of 3,3-diaminobenzidine tetrahydrochloride (DAB), generating a
precipitate sensitive to osmium tetroxide staining that can be visualized by
transmission electron microscopy. The TC tag is fused to the nucleocapsid protein
NCp7, a nucleic acid chaperone that binds to the viral genome. HeLa cells,
infected by ReAsH-labeled pseudoviruses containg NCp7-TC proteins exhibit strong
fluorescent cytoplasmic spots that overlap with dark precipitates in the TEM
sections. The DAB precipitates corresponding to single viral cores are observed
all over the cytoplasm, and notably near microtubules and nuclear pores. This
work describes for the first time a specific contrast given by HIV-1 viral
proteins in TEM images and opens new perspectives for the use of CLEM to monitor
the intracellular traffic of viral complexes.
PMID- 29938686
TI - Compressed sensing based CT reconstruction algorithm combined with modified Canny
edge detection.
AB - Given that the computed tomography (CT) reconstruction algorithm based on
compressed sensing (CS) results in blurred edges, we propose a modified Canny
operator that assists the CS algorithm to accurately capture an object's edge, to
preserve and further enhance the contrasts in the reconstructed image, thereby
improving image quality. We modified two procedures of the traditional Canny
operator, namely non-maximum suppression and edge tracking by hysteresis
according to the characteristics of low-dose CT reconstruction, and proposed two
major modifications: double-response edge detection and directional edge
tracking. The newly modified Canny operator was combined with the CS
reconstruction algorithm to become an edge-enhanced CS (EECS). Both a 2D Shepp
Logan phantom and a 3D dental phantom were used to conduct reconstruction
testing. Root-mean-square error, peak signal-to-noise ratio, and universal
quality index were employed to verify the reconstruction results. Qualitative and
quantitative results of EECS reconstruction showed its superiority over
conventional CS or CS combined with different edge detection techniques, such as
Laplacian, Prewitt, Sobel operators, etc. The experiments verified that the
proposed modified Canny operator is able to effectively detect the edge location
of an object during low-dose reconstruction, enabling EECS to reconstruct images
with better quality than those produced by other algorithms.
PMID- 29938687
TI - Exciton-plasmon hybrids for surface catalysis detected by SERS.
AB - Surface plasmons (SPs), in which the free electrons are collectively excited on
the metal surface, have been successfully used in chemical analysis and signal
detection. Generally, SPs possess two types of decay channels. SPs decay either
nonradiatively via the generation of hot electrons or radiatively through re
emitted photons, which can trigger surface chemical reactions when the molecules
are adsorbed on the surface of metal nanoparticles. An excitation light with a
special wavelength is irradiated on the surface of the plasmonic nanostructure,
the strong coupling interaction between electrons and light will then occur on
this, and this is followed by the development of a series of unique properties.
2D materials have been a hot topic of research for more than a decade, since
graphene was found in 2004. Recently, the combination of graphene with metal NPs
has been shown to possess many supernormal advantages, such as high stability and
catalytic activity, which have been successfully applied in plasmon-exciton co
driven chemical reactions.
PMID- 29938688
TI - A hybrid simulation framework for computer simulation and modelling studies of
grating-based x-ray phase-contrast images.
AB - Clinical studies performed using computer simulation are inexpensive, flexible
methods that can be used to study aspects of a proposed imaging technique prior
to a full clinical study. Typically, lesions are simulated into (experimental)
data to assess the clinical potential of new methods or algorithms. In grating
based phase-contrast imaging (GB-PCI), full wave simulations are, however,
computationally expensive due to the high periodicity of the gratings and
therefore not practically applicable when large data sets are required. This work
describes the development of a hybrid modelling platform that combines analytical
and empirical input data for a more rapid simulation of GB-PCI images with little
loss of accuracy. Instead of an explicit implementation of grating details,
measured summary metrics (i.e. visibility, flux, noise power spectra, presampling
modulation transfer function) are applied in order to generate transmission and
differential phase images with large fields of view. Realistic transmission and
differential phase images were obtained with good quantitative accuracy. The
different steps of the simulation framework, as well as the methods to measure
the summary metrics, are discussed in detail such that the technique can be
easily customized for a given system. The platform offers a fast, accurate
alternative to full wave simulations when the focus switches from grating/system
design and set up to the generation of GB-PCI images for an established system.
PMID- 29938689
TI - Detection of dose delivery variations on TomoTherapy using on-board detector
based verification.
AB - A clinical case of delivery dose deviations on a TomoTherapy treatment was
discovered during a patient specific treatment quality assurance (QA)
verification. An in-house developed QA system, MCLogQA, for TomoTherapy has been
implemented in our clinic for patient specific treatment QA. The MCLogQA system
utilizes the log file and detector-based multileaf collimator (MLC) leaf opening
time (LOT) to assess accuracy of treatment plan delivery. Recently, the MCLogQA
system discovered >10% dose deviation for a low dose/fraction treatment plan. To
verify the adequacy of the MCLogQA result, a delivery quality assurance (DQA)
plan was created and performed. The treatment plan was also transferred to a
second TomoTherapy unit and planning system to investigate if the plan-delivery
deviation was unit dependent. Further testing was carried out in phantom plans.
MCLogQA showed MLC LOT was on average 2.4% higher than the planned LOT, resulting
in 3.5% increase in mean dose, and 14% increase in dose to 1 cc volume of max
dose in PTV. Independent DQA verification confirmed the MCLogQA result. For the
transferred treatment plan delivery, the MCLogQA also showed an average increase
of 6.6% in MLC LOT, resulting in increases in mean dose by 9.3% and dose to 1 cc
volume of max dose in PTV by 16%. The inaccurate MLC LOT was a result of a poor
latency model at very small LOT. Phantom testing confirmed low LOT will result in
relatively large dosimetric variation, and detector-based MCLogQA will detect
differences in planned and measured LOT. Accuracy in TomoTherapy treatment
delivery can be susceptible to LOT uncertainty. Using MCLogQA for QA verification
not only validates the treatment delivery, but also provides information on LOT
variation and comprehensive dose distribution. This information can help decision
making when large plan-delivery deviation occurs.
PMID- 29938690
TI - Association of Bone Morphogenetic Protein (BMP)/Smad Signaling Pathway with
Fracture Healing and Osteogenic Ability in Senile Osteoporotic Fracture in Humans
and Rats.
AB - BACKGROUND To investigate the effect of the BMP/Smad signaling pathway on
fracture healing and osteogenic ability in senile osteoporotic fracture on humans
and rats. MATERIAL AND METHODS Sixty-two patients and well-matched normal
controls were enrolled for clinical observation. A rat model of senile
osteoporotic fracture was established. Serum BMP2 and Smad4 levels, as well as
alkaline phosphatase (ALP) activity, were detected by ELISA. Fracture healing was
observed by X-ray radiography and bone formation was analyzed by micro-CT.
RESULTS Serum BMP2 and Smad4 levels in patients with senile osteoporotic fracture
were significantly lower than those in normal controls (all P<0.01). BMP2 was
highly positively correlated with Smad4 in patients with senile osteoporotic
fracture (r=0.738). Compared with patients with low serum BMP2 and Smad4 levels,
visual analog scale scores decreased, bone mineral density (BMD) increased, and
duration of fracture healing was shortened in patients with high levels (all
P<0.05). Compared with the Model group, serum BMP2 and Smad4 levels increased,
fracture healing was improved, BMD, trabecular bone volume (TBV), tissue volume
(TV), bone volume fraction (BV/TV), mean trabecular thickness (Tb. Th), and mean
number of trabecular bone (Tb. N) were increased, and ALP activity increased in
the BMP2 overexpression group (all P<0.05), while each index in the NC group
showed no statistical difference relative to rats in the Model group (all
P>0.05). CONCLUSIONS BMP2 overexpression can promote fracture healing and
osteogenic ability in senile osteoporotic fractures through activating the
BMP/Smad signaling pathway.
PMID- 29938691
TI - [Polio and post-polio syndrome, viewed by patients and health professionals in
primary care].
AB - OBJECTIVE: Polio affects the quality of life of those who have suffered from it
and causes health problems including the post-polio syndrome. The main goals of
this work were to know the patients perspective of how they have been affected by
the disease and establish the knowledge of post-polio syndrome among patients and
primary health care professionals. METHODS: Interpretive qualitative research
based on the Grounded Theory carried out in two health-care centers in the city
of Malaga, one of them with care-rural clinics. Four focal groups were
established with the participation of thirteen patients and two focus groups with
twenty-six professional participants. Intentional sampling is performed until
saturation. The analysis follows an inductive strategy using the Atlas Ti5.2
software. RESULTS: The people affected by polio reports their personal histories
of suffering counteracted by strong family support and an active coping attitude,
marked by great effort exertion, willpower and endurance. These people made a
positive assessment of their lives minimising the limitations. They presented
compatible symptoms with post-polio syndrome, which remain unidentified due to
the lack of knowledge of it among patients and health-care professionals. The
health care provided was considered deficient due to several causes as for
instance lack of involvement, communication problems. CONCLUSIONS: The day-to-day
polio experience is focused on personal overcoming with major roles played by
family support, difficult relationships with the healthcare system and lack of
knowledge of the post-polio syndrome.
PMID- 29938692
TI - Publisher Correction: Demonstration of qubit operations below a rigorous fault
tolerance threshold with gate set tomography.
AB - This corrects the article DOI: 10.1038/ncomms14485.
PMID- 29938693
TI - Publisher Correction: Abrupt cooling over the North Atlantic in modern climate
models.
AB - This corrects the article DOI: 10.1038/ncomms14375.
PMID- 29938694
TI - Publisher Correction: Giant heat transfer in the crossover regime between
conduction and radiation.
AB - This corrects the article DOI: 10.1038/ncomms14475.
PMID- 29938695
TI - Author Correction: Thermogenesis-triggered seed dispersal in dwarf mistletoe.
AB - This corrects the article DOI: 10.1038/ncomms7262.
PMID- 29938696
TI - Publisher Correction: Intensity-dependent modulation of optically active signals
in a chiral metamaterial.
AB - This corrects the article DOI: 10.1038/ncomms14602.
PMID- 29938698
TI - 2017 Reviewer acknowledgments.
PMID- 29938697
TI - Publisher Correction: Study of radiative heat transfer in Angstrom- and nanometre
sized gaps.
AB - This corrects the article DOI: 10.1038/ncomms14479.
PMID- 29938699
TI - NICU Network Neurobehavioral Scale: 1-month normative data and variation from
birth to 1 month.
AB - BackgroundThe Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
is a standardized method for infant neurobehavioral assessment. Normative values
are available for newborns, but the NNNS is not always feasible at birth.
Unfortunately, 1-month NNNS normative data are lacking.AimsTo provide normative
data for the NNNS examination at 1 month and to assess birth-to-one-month changes
in NNNS summary scores.Study designThe NNNS was administered at birth and at 1
month within a longitudinal prospective study design.SubjectsA cohort of 99
clinically healthy full-term infants were recruited from a well-child
nursery.Outcome measuresBirth-to-1-month NNNS variations were evaluated and the
association of neonatal and sociodemographic variables with the rate of change of
NNNS summary scores were investigated.Results and conclusionsNNNS scores from the
10th to the 90th percentile represent a range of normative performance at 1
month. A complex pattern of stability and change emerged comparing NNNS summary
scores from birth to 1 month. Orienting, Regulation, and Quality of movements
significantly increased, whereas Lethargy and Hypotonicity significantly
decreased. Birth-to-1-month changes in NNNS performance suggest improvements in
neurobehavioral organization. These data are useful for research purposes and for
clinical evaluation of neurobehavioral performance in both healthy and at-risk 1
month-old infants.
PMID- 29938701
TI - A Comprehensive Development Agenda on Tenofovir Alafenamide in Clinical Practice.
AB - The introduction of tenofovir (TFV) alafenamide (TAF) into clinical practice will
be a further revolution in antiretroviral therapy. Currently available HIV-1
regimens are wide enough to allow diversified usage in different settings.
Despite the fact that TAF is not capillary accessible, even in industrialized
countries, ultimate International Guidelines have already included TAF in
backbone or in single-tablet regimens. Due to a better safety profile, TAF will
progressively replace TFV disoproxil fumarate, both in naive and experienced
patients. However, therapeutic innovations have to deal with budget constraints
and different global spending-review patterns. The aim of this article is to give
a comprehensive agenda of TAF use in naive and experienced HIV-1 infected
patients, providing a full review of the studies present in the literature and
contextualizing these findings into daily clinical practice.
PMID- 29938702
TI - Is UNAIDS 90-90-90 target a Dream or a Reality for Middle East and North Africa
Region on Ending the AIDS Epidemic? A Review Study.
AB - Middle East and North Africa (MENA) region is lagging far behind the global
average to reach 90-90-90 targets. This study uses the UNAIDS 90-90-90 program to
evaluate the HIV current situation in MENA countries, and understand the
challenges that exist in the way of approaching the program goals. All articles
and publications were searched based on the 90-90-90 program indexes among
national and international data resources such as official national reports and
online scientific databases such as PubMed, Medline, and Scopus up to December
2017. The data were categorized into four main stages: (1) estimated number of
HIV-positive people (people living with HIV [PLWH]); (2) PLWH who know their
status; (3) PLWH receiving antiretroviral therapy (ART); and (4) virally
suppressed PLWH. A total of 41 papers were included in the study. 19 out of 24
MENA countries have met the inclusion criteria. The proportion of diagnosed
people ranges from 6% in Pakistan to 76% in Algeria. The percentage of diagnosed
people receiving ART ranges between 7% in Pakistan and 86% in Algeria. Viral
suppression levels vary from 4% to 72% in Pakistan and Kuwait, respectively. Lack
of appropriate surveillance systems, low access to HIV-care facilities along with
complicated socioeconomic and geopolitical situation of the region have made it
challenging for MENA countries to reach 90-90-90 goals by 2020. To achieve these
goals, the foremost strategy is global effort to establish peace in this region
and rebuild the infrastructure in the countries involved in war and to setup
comprehensive surveillance systems in the majority of the MENA countries.
PMID- 29938703
TI - The Role of HIV in the Progression through the Stages of the Human Papillomavirus
to Cervical Cancer Pathway.
AB - Globally, an estimated 36.9 million persons are living with HIV/AIDS, and
approximately 291 million women worldwide are carriers of human papillomavirus
(HPV). A large number of women currently infected with either or both viruses
constitute a large burden on the national health care system. Women with HIV have
significantly higher rates of HPV infections than women without HIV.
Approximately 77% of women with HIV are carriers of HPV. While research has
established a linkage between HIV and progression to cervical cancer in general,
there are currently no review articles exploring the role HIV has in the
progression from HPV to each stage of carcinogenesis that leads to cervical
cancer. The objective of this review is to examine the relationship between HIV
and progression from HPV to each stage of carcinogenesis related to cervical
cancer. The findings of the review support the conclusion that HIV infection
increases the likelihood of progression to each stage of the HPV to cervical
cancer pathway.
PMID- 29938704
TI - HIV/AIDS in Sierra Leone: Characterizing the Hidden Epidemic.
AB - Sierra Leone is a low-income West African country that has dealt with waves of
economic, political, and public health challenges in its recent past, including a
decade-long brutal civil war and the Ebola epidemic of 2014-2016. The HIV/AIDS
epidemic, which has raged on in the country since 1987, has long been
characterized as stable. The latest UNAIDS report estimates a countrywide HIV
prevalence rate of 1.7% in 2016 among adults aged 15-49 years. However, there are
indications that the epidemic may be in fact escalating and unless arrested
urgently, has the potential to deteriorate into a major public health emergency.
Although there are high levels of HIV awareness among adults (over 94%), uptake
in voluntary HIV testing has remained low (<30%), and under one-third (29%) of
the country's 60,000 people living with HIV/AIDS were on antiretroviral therapy
in 2015. This review attempts to address the paucity of scientific information on
the subject by presenting the historical and epidemiological background to the
HIV/AIDS epidemic in Sierra Leone. Other aspects of the HIV/AIDS epidemic in
Sierra Leone are examined, including routine HIV screening and diagnosis, linkage
to and retention in HIV care, clinical characteristics and molecular
epidemiology, treatment coverage, and prevention strategies. Finally, we identify
four key areas of challenge that are hampering current efforts attempting to
bring the epidemic under control, and perspective is offered on the way forward.
PMID- 29938705
TI - Prevalence of Tuberculosis in HIV-positive Prisoners: A Systematic Review and
Meta-analysis.
AB - : Tuberculosis (TB) and HIV constitute the main burden of infectious diseases
worldwide. Imprisonment is an important risk factor for contracting TB,
especially among those living with HIV. This systematic review summarizes the
available data on the prevalence of TB among HIV-positive prisoners; which may
support improved targeted TB/HIV prevention plans. We electronically examined
published studies up to December 2017 with the aim of finding articles that
investigated the prevalence of TB in HIV-positive prisoners. MEDLINE, SCOPUS,
Embase, and Web of Science electronic databases were searched with no restriction
on language or time. A random effects model was used to conduct the meta-analysis
and generate a summary estimate for the global prevalence of TB among HIV
positive prisoners; and subgroup estimates by continent. The meta-analysis
included 22 studies published from 1992 to 2016. In total, 2,465 articles were
retrieved and 22 papers met inclusion criteria. Eligible papers contained 220,101
prisoners, with 1,611 cases of TB in 6,126 HIV-positive subjects. Globally, the
pooled prevalence of TB in HIV-positive prisoners was 32.6% [95% confidence
interval (CI): 27.5% to 38.2%; p-value for heterogeneity=0.001]. Results of the
subgroup analysis by continent were as follows: Africa, 14% (CI: 8% to 24%);
North/South America, 37% (CI: 31% to 44%); Asia, 35% (CI: 12% to 68%); and
Europe, 25% (CI: 12% to 45%). CONCLUSIONS: The prevalence of TB among HIV
positive prisoners is high worldwide. Screening of TB in this population is
essential for the treatment of both diseases. Syndemics of TB and HIV in
prisoners during the past three decades have created an alarming situation across
the world. Hence, coordinated policies are essential for the early identification
and effective treatment of this vulnerable population.
PMID- 29938706
TI - Hot News: Hepatitis B Gene Therapy Coming to Age.
AB - The major pandemics caused by chronic viral infections is produced by HIV,
hepatitis C virus (HCV), and hepatitis B virus (HBV), with estimates of 38, 70,
and 250 million people worldwide, respectively (Fig. 1). During the last couple
of years, the advent of direct oral antivirals has allowed pursuing global HCV
eradication. In an unprecedented manner, these drugs cure more than 95% of
hepatitis C patients when given for only 2-3 months. The enthusiasm on HCV has
renewed the interest for curative strategies for both HIV and HBV. However,
important biological differences between all three viruses may preclude
envisioning a similar rapid success for either HIV or HBV than for HCV infection.
As shown in figure 1, once infection of targeted cells has occurred, the viral
genetic material only replicates in the cytosol for HCV whereas it enters the
nucleus and integrates into the chromosomes as provirus for HIV or is converted
in a circular covalently closed form (cccDNA) for HBV (Fig. 1). Blocking viral
nucleic acid replication for a minimum lag of time allows definitive clearance of
HCV infection, with degradation of residual cytoplasmic HCV-RNA strands. In
contrast, blocking viral replication has only a transient effect on HIV or HBV,
as mRNA expression resumes following treatment discontinuation, given the
stability of the HIV provirus or the HBV cccDNA, respectively. The European Liver
meeting took held in Paris on April 2018. A relatively large number of
presentations addressed distinct new hepatitis B therapeutic strategies. Table 1
summarizes some of the molecules that have been investigated so far with more
promising results, grouping them into distinct drug classes (Soriano et al. Exp
Op Inv Drugs 2017;26:843-51), based on their distinct mechanism of action and
targeted steps in the HBV life cycle (Fig. 2). Considering the pros and cons of
novel HBV therapeutic candidates, it has become apparent new HBV gene therapies
among the most attractive. Several advances have contributed to position gene
therapy in front within the experimental HBV armamentarium. First, progresses in
delivery systems, including the use of polymers and nanoformulations have allowed
developing easier forms of administration that now are becoming subcutaneous and
monthly. Second, the synthetic production of oligonucleotide formulations has
reduced costs. Third, the specificity against HBV is higher than for other
experimental agents, as immune modulators that enhance innate immunity, such as
TLR agonists (i.e., GS-9620) or checkpoint inhibitors (i.e., nivolumab). Fourth,
significant declines in serum hepatitis B surface antigen (HBsAg) are
demonstrated during gene therapy, which have never been seen using the most
potent polymerase inhibitors (i.e., tenofovir or entecavir). Finally,
unanticipated significant reductions in cccDNA are seen with HBV gene therapy,
most likely as prove of an indirect benefit of waning the immunosuppressive
effect of large over amounts of HBsAg released by infected hepatocytes that
contributes to T-cell exhaustion. In a pioneering study, Roche was the first to
publish the potent effect of an oral small molecule that blocked HBV gene
expression (Mueller et al. J Hepatol 2018;68:412-20). The drug belonged to the
dihydroquinolizinone class, and directly or indirectly modified viral RNAs,
promoting their degradation. This posttranscriptional silencing was accompanied
by rapid drops in HBV-DNA and more importantly in serum HBsAg in the humanized
mice. However, Roche decided to discontinue any further clinical development of
the drug. Nowadays, two major groups of agents are being developed as HBV gene
therapies. At this time, interference RNA (iRNA) molecules and nucleic acid
polymers (NAPs) are the most promising. Overall, iRNA is double-stranded RNA
molecules, 20 nucleotides long. One strand matches a segment of specific HBV mRNA
and induces its degradation. Several iRNA molecules have entered into Phase II
clinical trials (Flisiak et al. Exp Op Biol Ther, in press), including ARB-1467
and AB-729 (Arbutus), ARO-HBV (Arrowhead), ALN-HBV (Alnylam), and IONIS-HBVRx
(Ionis). In most cases, they are tested as part of combination therapy with
nucleos(t)ide analogs and/or peginterferon. NAPs are phosphorothioate 40 length
oligonucleotides that no map any HBV sequence. However, they interact with a
liver host target protein (apolipoprotein-like) and result in specific inhibition
of HBV mRNAs. This is followed by rapid suppression of HBsAg release (Roehl et
al. Mol Ther Nuc Acids 2017;8:1-12). In a pilot study with intravenous REP-2139,
investigators from Replicor demonstrated strong reductions in HBV-DNA along with
significant drops in HBsAg and seroconversion in some patients. More
interestingly was the recognition of significant reductions in hepatic cccDNA,
most likely a result of an indirect effect following the removal of large amounts
of HBsAg from the bloodstream that contributes to impaired T-cell responses in
chronic hepatitis B patients (Bazinet et al. EASL, Paris 2018; abstract FRI-343).
An improved NAP, named REP-2165 and subcutaneous administration are currently
being tested.
PMID- 29938707
TI - Hot News: Dr. Robert Redfield Appointed as New CDC Director.
AB - Well-known AIDS researcher Robert Redfield picked to lead the CDC on March 2018.
He is one of the HIV/AIDS pioneers in the United States. During two decades at
the Walter Reed Army Institute of Research, in Bethesda, MD, he made pivotal
contributions, highlighting the importance of heterosexual HIV transmission,
developing the Walter Reed staging system for HIV infection, and demonstrating
that active HIV replication takes place during all stages of HIV disease. In
1996, he was one of the cofounders of the Institute of Human Virology in
Baltimore, MD. Nowadays, he was running a treatment network for HIV and hepatitis
C patients. With this background, he would be well prepared to combat one of the
DHHS and CDC's top priorities, the opioid epidemic (Kolodny et al. JAMA
2017;318:1537-8). In an interview, Robert Gallo, director of the Institute of
Human Virology, said "Redfield is a dedicated and compassionate physician who
truly cares about his patients and is deeply committed to ensuring patients
receive the highest quality of care possible. Dr. Redfield has served his country
well, and consistently demonstrates strong public health instincts that are
grounded in science and clinical medicine. In my view, despite the loss to our
institute, I believe this makes him the ideal candidate to direct the CDC".
PMID- 29938708
TI - Findings of Research Misconduct.
PMID- 29938709
TI - A Case of Refractory Pulmonary Coccidioidomycosis Successfully Treated with
Posaconazole Therapy.
AB - Coccidioidomycosis is an endemic fungal infection caused by the inhalation of the
spores of Coccidioides species. Patients with underlying immunosuppressive
illness can contract chronic or disseminated disease which requires prolonged
systemic therapy. Pulmonary coccidioidomycosis remains as an illusory and
abstruse disease, with increased prevalence that poses as a challenge for
clinicians in developing an effective strategy for treatment. Here, we report
successful treatment of a refractory case of chronic relapsing pulmonary
coccidioidomycosis in a 50-year old woman with a thin-walled cavitary lung lesion
who was ultimately treated with posaconazole.
PMID- 29938710
TI - Surface fluid registration and multivariate tensor-based morphometry in newborns
the effects of prematurity on the putamen.
AB - Many disorders that affect the brain can cause shape changes in subcortical
structures, and these may provide biomarkers for disease detection and
progression. Automatic tools are needed to accurately identify and characterize
these alterations. In recent work, we developed a surface multivariate tensor
based morphometry analysis (mTBM) to detect morphological group differences in
subcortical structures, and we applied this method to study HIV/AIDS, William's
syndrome, Alzheimer's disease and prematurity. Here we will focus more
specifically on mTBM in neonates, which, in its current form, starts with
manually segmented subcortical structures from MRI images of a two subject
groups, places a conformal grid on each of their surfaces, registers them to a
template through a constrained harmonic map and provides statistical comparisons
between the two groups, at each vertex of the template grid. We improve this
pipeline in two ways: first by replacing the constrained harmonic map with a new
fluid registration algorithm that we recently developed. Secondly, by optimizing
the pipeline to study the putamen in newborns. Our analysis is applied to the
comparison of the putamen in premature and term born neonates. Recent whole-brain
volumetric studies have detected differences in this structure in babies born
preterm. Here we add to the literature on this topic by zooming in on this
structure, and by generating the first surface-based maps of these changes. To do
so, we use a dataset of manually segmented putamens from T1-weighted brain MR
images from 17 preterm and 18 term-born neonates. Statistical comparisons between
the two groups are performed via four methods: univariate and multivariate tensor
based morphometry, the commonly used medial axis distance, and a combination of
the last two statistics. We detect widespread statistically significant
differences in morphology between the two groups that are consistent across
statistics, but more extensive for multivariate measures.
PMID- 29938711
TI - Multimodal Ambulatory Sleep Detection.
AB - Inadequate sleep affects health in multiple ways. Unobtrusive ambulatory methods
to monitor long-term sleep patterns in large populations could be useful for
health and policy decisions. This paper presents an algorithm that uses
multimodal data from smartphones and wearable technologies to detect sleep/wake
state and sleep episode on/offset. We collected 5580 days of multimodal data and
applied recurrent neural networks for sleep/wake classification, followed by
cross-correlation-based template matching for sleep episode on/offset detection.
The method achieved a sleep/wake classification accuracy of 96.5%, and sleep
episode on/offset detection F1 scores of 0.85 and 0.82, respectively, with mean
errors of 5.3 and 5.5 min, respectively, when compared with sleep/wake state and
sleep episode on/offset assessed using actigraphy and sleep diaries.
PMID- 29938712
TI - Identifying Relationships in Functional and Structural Connectome Data Using a
Hypergraph Learning Method.
AB - The brain connectome provides an unprecedented degree of information about the
organization of neuronal network architecture, both at a regional level, as well
as regarding the entire brain network. Over the last several years the
neuroimaging community has made tremendous advancements in the analysis of
structural connectomes derived from white matter fiber tractography or functional
connectomes derived from time-series blood oxygen level signals. However,
computational techniques that combine structural and functional connectome data
to discover complex relationships between fiber density and signal
synchronization, including the relationship with health and disease, has not been
consistently performed. To overcome this shortcoming, a novel connectome feature
selection technique is proposed that uses hypergraphs to identify connectivity
relationships when structural and functional connectome data is combined. Using
publicly available connectome data from the UMCD database, experiments are
provided that show SVM classifiers trained with structural and functional
connectome features selected by our method are able to correctly identify autism
subjects with 88 % accuracy. These results suggest our combined connectome
feature selection approach may improve outcome forecasting in the context of
autism.
PMID- 29938713
TI - Statistical analysis of relative pose of the thalamus in preterm neonates.
AB - Preterm neonates are at higher risk of neurocognitive and neurosensory
abnormalities. While numerous studies have looked at the effect of prematurity on
brain anatomy, none to date have attempted to understand the relative pose of
subcortical structures and to assess its potential as a biomarker of abnormal
growth. Here, we perform the first relative pose analysis on a point distribution
model (PDM) of the thalamus between 17 preterm and 19 term-born healthy neonates.
Initially, linear registration and constrained harmonic registration were
computed to remove the irrelevant global pose information and obtain
correspondence in vertices. All the parameters for the relative pose were then
obtained through similarity transformation. Subsequently, all the pose parameters
(scale, rotation and translation) were projected into a log-Euclidean space,
where univariate and multivariate statistics were performed. Our method detected
relative pose differences in the preterm birth for the left thalamus. Our results
suggest that relative pose in subcortical structures is a useful indicator of
brain injury, particularly along the anterior surface and the posterior surface.
Our study supports the concept that there are regional thalamic asymmetries in
the preterm that may be related to subtle white matter injury, have prognostic
significance, or be related to preterm birth itself.
PMID- 29938714
TI - Identifying High Order Brain Connectome Biomarkers via Learning on Hypergraph.
AB - The functional connectome has gained increased attention in the neuroscience
community. In general, most network connectivity models are based on correlations
between discrete-time series signals that only connect two different brain
regions. However, these bivariate region-to-region models do not involve three or
more brain regions that form a subnetwork. Here we propose a learning-based
method to explore subnetwork biomarkers that are significantly distinguishable
between two clinical cohorts. Learning on hypergraph is employed in our work.
Specifically, we construct a hypergraph by exhaustively inspecting all possible
subnetworks for all subjects, where each hyperedge connects a group of subjects
demonstrating highly correlated functional connectivity behavior throughout the
underlying subnetwork. The objective function of hypergraph learning is to
jointly optimize the weights for all hyperedges which make the separation of two
groups by the learned data representation be in the best consensus with the
observed clinical labels. We deploy our method to find high order childhood
autism biomarkers from rs-fMRI images. Promising results have been obtained from
comprehensive evaluation on the discriminative power and generality in diagnosis
of Autism.
PMID- 29938715
TI - Influence of number of drugs on olfaction in the elderly.
AB - BACKGROUND: The etiology of age-related olfactory loss is still unclear, but it
has been claimed that polypharmacotherapy may contribute to olfactory
dysfunction, particularly in the elderly, who are more likely to need multiple
drugs. The present pilot study investigated the relationship between smell and
the number and type of drugs taken in a group of elderly. METHODOLOGY: 50 elderly
volunteers (over 64 years old) who were healthy from the sinonasal standpoint
(SNOT-22 under 1) and had no cognitive impairments [Mini Mental State Examination
(MMSE over 18) were administered the Screening 12 test and tested on their n
butanol olfactory threshold. Their olfactory performance was then connected with
the number and type of drugs participants used. RESULTS: The mean age of the
included volunteers was 74 plus/minus 7 years. No association emerged between
odor identification and number of drugs taken. The number of drugs taken
correlated directly with a worse olfactory threshold and with a worse MMSE score,
meaning a worse cognitive status. Odor identification significantly worsened with
age. Comparing those volunteers taking only one drug known to not influence
olfaction with another sub-group of volunteers taking five or more drugs, it was
evident that subjects taking only one drug scored significantly better in
olfactory threshold test and MMSE, and marginally better in olfactory
identification test. For what concerns the difference between male and female
volunteers, no difference in olfactory test result was shown, both for threshold
and identification. Univariate analysis showed a direct correlation between the
consumption of calcium channel blockers, beta-blockers, acetylsalicylic acid and
olfactory threshold, meaning a worse sense of smell. Acetylsalicylic acid also
correlated inversely with odor identification, meaning again a worse sense of
smell, and so did potassium-sparing diuretics. Multivariate analysis showed that
MMSE scores correlated with a better sense of smell, that is a lower olfactory
threshold, and that beta-blockers and acetylsalicylic acid negatively affected
olfactory threshold, meaning a worse sense of smell. Acetylsalicylic acid also
correlated inversely with odor identification, meaning again a worse sense of
smell. CONCLUSIONS: The number of drugs taken demonstrated to be significantly
correlated with a worse olfactory threshold and worse MMSE. Larger studies on
elderly volunteers are needed to confirm these preliminary findings.
PMID- 29938720
TI - Effects of tuning the applied voltage pulse periods on the electroluminescence
spectra of host-guest white light-emitting electrochemical cells.
AB - Solid-state white light-emitting electrochemical cells (LECs) are potential
candidates in solid-state lighting due to their promising advantages of simple
device structure, low-voltage operation and compatibility with inert cathode
metals. Adjusting the correlated color temperature (CCT) of background
illumination is highly desired for modern smart lighting systems. In this work, a
novel technique to tune the CCT of electroluminescence (EL) from white LECs is
proposed. Color tuning is based on adjusting the applied voltage pulse period on
the host-guest white LECs and the working mechanism is illustrated. A shorter
voltage pulse period is insufficient to completely charge the capacitive LEC
device and thus the effective voltage applied on the device is lower. Since the
host-guest energy level offsets favor carrier trapping, a lower effective applied
voltage results in a more pronounced guest emission, rendering redder white EL
with a lower CCT. On the other hand, a longer voltage pulse period facilitates
more complete charging and the effective voltage applied on the white LEC is
higher. A higher bias facilitates direct exciton formation on the host molecule
and subsequent partial host-guest energy transfer generates bluer white EL with a
higher CCT. By tuning the voltage pulse period from 0.2 to 20 ms, the CCT of EL
resulting from white LECs ranges from 2482 to 5723 K. The CCT tuning range is
sufficient for general lighting applications. In contrast to color tuning of
white LECs under constant-voltage driving, in which >10* brightness enhancement
is accompanied by higher-CCT white EL, the discharging half-period in pulse
voltage driving provides relaxation time to turn off the device and reduces the
average brightness of the white LECs driven under a longer voltage pulse period.
Therefore, similar brightness can be achieved for white EL with different CCTs.
No additional optical filtering device is needed for this novel color tuning
technique and it has potential for use in solid-state lighting.
PMID- 29938721
TI - Small-angle X-ray scattering study on nano-scale structures controlled by water
content in a binary water/ionic liquid system.
AB - We report the water-in-ionic-liquid microemulsions (ME) formed in a binary
water/ionic liquid system, without organic solvents, using a surfactant ionic
liquid (SAIL) based on 1-butyl-3-methylimidazolium (C4mIm+) as the cation and
dioctyl sulfosuccinate (AOT-) as the anion. Small-angle X-ray scattering (SAXS)
revealed that MEs were stably formed in the binary water/SAIL solutions in the
low water content region (water volume fraction, phiw < 0.1), and the ME size
systematically increased with increasing phiw. We further investigated the
nanostructures of the high phiw region using a combination of SAXS and
rheological measurements and found that the MEs changed to a stacked lamellar
structure comprising SAIL bilayers and water phases at phiw > 0.12. At the
largest water content, phiw = 0.99, vesicle structures were obtained.
PMID- 29938722
TI - Silkworm silk-based materials and devices generated using bio-nanotechnology.
AB - Silks are natural fibrous protein polymers that are spun by silkworms and
spiders. Among silk variants, there has been increasing interest devoted to the
silkworm silk of B. mori, due to its availability in large quantities along with
its unique material properties. Silk fibroin can be extracted from the cocoons of
the B. mori silkworm and combined synergistically with other biomaterials to form
biopolymer composites. With the development of recombinant DNA technology, silks
can also be rationally designed and synthesized via genetic control. Silk
proteins can be processed in aqueous environments into various material formats
including films, sponges, electrospun mats and hydrogels. The versatility and
sustainability of silk-based materials provides an impressive toolbox for
tailoring materials to meet specific applications via eco-friendly approaches.
Historically, silkworm silk has been used by the textile industry for thousands
of years due to its excellent physical properties, such as lightweight, high
mechanical strength, flexibility, and luster. Recently, due to these properties,
along with its biocompatibility, biodegradability and non-immunogenicity,
silkworm silk has become a candidate for biomedical utility. Further, the FDA has
approved silk medical devices for sutures and as a support structure during
reconstructive surgery. With increasing needs for implantable and degradable
devices, silkworm silk has attracted interest for electronics, photonics for
implantable yet degradable medical devices, along with a broader range of utility
in different device applications. This Tutorial review summarizes and highlights
recent advances in the use of silk-based materials in bio-nanotechnology, with a
focus on the fabrication and functionalization methods for in vitro and in vivo
applications in the field of tissue engineering, degradable devices and
controlled release systems.
PMID- 29938727
TI - Fast synthesis of Co1.8V1.2O4/rGO as a high-rate anode material for lithium-ion
batteries.
AB - A fast and facile approach to synthesize ultrasmall Co1.8V1.2O4 nanoparticles
with an average size of 8.4 nm grown on rGO was successfully developed. The novel
Co1.8V1.2O4/rGO composite anode exhibits excellent rate performance for lithium
ion batteries, delivering a high discharge capacity of 628 mA h g-1 at 2000 mA g
1.
PMID- 29938725
TI - A catalytic allylic cation-induced intermolecular allylation-semipinacol
rearrangement.
AB - A catalytic intermolecular semipinacol rearrangement induced by allylic
carbocations has been realized. This tandem reaction is highly efficient under
the catalysis of ZnBr2, generating a wide range of alpha-homoallyl substituted
ketones which contain all-carbon quaternary centres in good to excellent yields
(up to 98%) with moderate to high diastereoselectivities (up to >20 : 1).
Synthetic application of this novel methodology in the construction of core
structures of natural products is also reported.
PMID- 29938729
TI - Coordination of the biliverdin D-ring in bacteriophytochromes.
AB - Phytochrome proteins translate light into biochemical signals in plants, fungi
and microorganisms. Light cues are absorbed by a bilin chromophore, leading to an
isomerization and a rotation of the D-ring. This relays the signal to the protein
matrix. A set of amino acids, which is conserved across the phytochrome
superfamily, holds the chromophore in the binding pocket. However, the functional
role of many of these amino acids is not yet understood. Here, we investigate the
hydrogen bonding network which surrounds the D-ring of the chromophore in the
resting (Pr) state. We use UV/vis spectroscopy, infrared absorption spectroscopy
and X-ray crystallography to compare the photosensory domains from Deinococcus
radiodurans, the phytochrome 1 from Stigmatella aurantiaca, and a D. radiodurans
H290T mutant. In the latter two, an otherwise conserved histidine next to the D
ring is replaced by a threonine. Our infrared absorption data indicate that the
carbonyl of the D-ring is more strongly coordinated by hydrogen bonds when the
histidine is missing. This is in apparent contrast with the crystal structure of
the PAS-GAF domain of phytochrome 1 from S. aurantiaca (pdb code 4RPW), which did
not resolve any obvious binding partners for the D-ring carbonyl. We present a
new crystal structure of the H290T mutant of the PAS-GAF from D. radiodurans
phytochrome. The 1.4 A-resolution structure reveals additional water molecules,
which fill the void created by the mutation. Two of the waters are significantly
disordered, suggesting that flexibility might be important for the
photoconversion. Finally, we report a spectral analysis which quantitatively
explains why the histidine-less phytochromes do not reach equal Pfr-type
absorption in the photoequilibrium compared to the Deinococcus radiodurans wild
type protein. The study highlights the importance of water molecules and the
hydrogen bonding network around the chromophore for controlling the isomerization
reaction and spectral properties of phytochromes.
PMID- 29938730
TI - A bifunctional cationic metal-organic framework based on unprecedented
nonanuclear copper(ii) cluster for high dichromate and chromate trapping and
highly efficient photocatalytic degradation of organic dyes under visible light
irradiation.
AB - A bifunctional cationic metal-organic framework {[Cu9(OH)6Cl2(itp)6(1,4
bdc)3](NO3)2(OH)2.20H2O}n (1-NO3-OH.20H2O) was synthesized and characterized (itp
= 1-imidazol-1-yl-3-(1,2,4-triazol-4-yl)propane, 1,4-bdc = 1,4
benzenedicarboxylate). In 1-NO3-OH.20H2O, three [Cu3(MU3-OH)(MU2-OH)] trimeric
clusters are bridged by two MU3-Cl and form a [Cu9(MU3-OH)3(MU2-OH)3(MU3-Cl)2]
cluster. Such a nonanuclear copper(ii) cluster [Cu9(MU3-OH)3(MU2-OH)3(MU3-Cl)2]
has not been reported till now, at least to the best of our knowledge. 1-NO3
OH.20H2O showed a 6-connected 2D 36-hxl net based on a nonanuclear copper(ii)
cluster [Cu9(MU3-OH)3(MU2-OH)3(MU3-Cl)2]. 1-NO3-OH.20H2O is also the first 2D 36
hxl net-based nonanuclear cluster. 1-NO3-OH (guest-free phase) showed fast and
highly efficient Cr2O72- and CrO42- trapping, and good recyclability for
capturing Cr2O72- and CrO42-. The adsorption capacities of 1-NO3-OH to capture
Cr2O72- and CrO42- were 1.762 mol mol-1 (154.8 mg g-1) and 1.896 mol mol-1 (89.5
mg g-1), respectively, at a molar ratio of 1 : 2 (1-NO3-OH to 2.5 * 10-3 mol L-1
Cr2O72- or CrO42-). 1-NO3-OH exhibited the selective sorption of Cr2O72- or CrO42
from a solution containing a mixture of Cr2O72- or CrO42- and a ten-fold molar
amount of ClO4-, NO3-, Cl-, BF4- or a five-fold molar amount of mol L-1 SO42-. 1
NO3-OH could capture 87.9% dilute Cr2O72- or 91.8% dilute CrO42- at an equimolar
1-NO3-OH to 20 ppm Cr2O72- or CrO42-. 1-NO3-OH.20H2O exhibited a highly efficient
photocatalytic degradation of the cationic organic dyes methylene blue (MB) and
rhodamine B (RhB) under visible light irradiation, and was shown to be a good
photocatalyst for photocatalytic degradation of the cationic organic dyes.
PMID- 29938731
TI - Engineering strategies for rational polyketide synthase design.
AB - Covering: mid 1990s to 2018 Over the last two decades, diverse approaches have
been explored to generate new polyketides by engineering polyketide synthases
(PKSs). Although it has been proven possible to produce new compounds by designed
PKSs, engineering strategies failed to make polyketides available via widely
applicable rules and protocols. Still, organic synthetic routes have to be
employed whenever new polyketides are needed for applications in medicine,
agriculture, and industry. In light of the rising demand for commodity products
from feedstock and for fast and cheap access to pharmaceutical compounds, the
need for harnessing PKSs to produce such molecules is more urgent than ever
before. In this review, we focus on a multitude of approaches to engineer modular
PKSs by swapping and replacing PKS modules and domains, which we analyze in the
light of recent structural and biochemical data. We conclude with an outlook on
possible strategies on how to increase success rates of PKS engineering in
future.
PMID- 29938735
TI - Encapsulating propeller-like columnar liquid crystals with an aromatic outer
shell: influence of phenoxy-terminated side chains on the phase behaviour of
triphenylbenzenes.
AB - Tailoring of phase transition temperatures of columnar liquid crystals by side
chain variation is often associated with an undesired change in the mesophase
type and/or geometry. To overcome this problem phenoxy-terminated side chains
rather than alkyl side chains were grafted onto triphenylbenzenes, which resulted
in reduced clearing points, while melting points were little affected. More
importantly, helical columnar self-assembly was not compromised.
PMID- 29938737
TI - Total synthesis and structural revision of (+/-)-nidemone.
AB - Total synthesis of the revised structure of (+/-)-nidemone has been accomplished
from 6-bromo-2-hydroxybenzaldehyde (5) in either six or eight synthetic steps in
6% and 10% overall yield, respectively, without using any protecting group. The
revised structure of nidemone was confirmed by single-crystal X-ray diffraction
analysis. Sonogashira coupling, regioselective hydrogenation, and an
intramolecular Stetter reaction were the key steps in the synthesis.
PMID- 29938738
TI - High progesterone levels on the day of HCG administration do not affect the
embryo quality and the reproductive outcomes of frozen embryo transfers.
AB - OBJECTIVES: The aim of this study was to evaluate the impact of pre- mature
progesterone rise on the day of human chorionic gonadotropin (hCG) administration
on the outcome of in vitro fertilization (IVF) of frozen embryo transfer (FET)
cycles using cleavage-stage embryos. METHODS: This was a retrospective, cohort
study of 131 ovarian stimulation cycles followed by cleavage-stage frozen embryo
transfers. The first group consisted of women undergoing FET due to premature
luteinization during controlled ovarian stimulation (n = 56, P >=1.2 ng/ml). The
controls were represented by women undergoing FET not complicated by high
progesterone levels at induction (n = 75, P < 1.2 ng/ml). For both groups, the
progesterone was measured on the day of hCG administration and the fertilization
rate, cleavage rate, implantation rate, clinical pregnancy rate, ongoing
pregnancy rate and Top-Quality Embryos (TQE) rates were compared. RESULTS: The
increase of progesterone in patients of the Group A had no significant effects on
the number of oocytes retrieved or available for the insemination. The
fertilization rate, cleavage rate and implantation rates, as well as the clinical
pregnancy rate and ongoing pregnancy were very similar in both study groups. The
analysis of TQE rates between the two groups indicated a roughly comparable
result. CONCLUSIONS: The results of this study showed that progesterone elevation
on the day of hCG administration did not affect the outcomes of IVF with frozen
embryos at cleavage stage. This study therefore confirms that for patients with
high progesterone levels the right way to obtain a healthy pregnancy should be to
delay the embryo transfer at a successive FET cycle, not associated with the
ovarian stimulation.
PMID- 29938739
TI - Fatigue Resistance of New and Used Nickel-Titanium Rotary Instruments: a
Comparative Study.
AB - OBJECTIVES: Aim of the present study was twofold. First, to evaluate in vitro,
the performance of two different NiTi rotary instruments in one molar case; then,
to evaluate their resistance to cyclic fatigue, compared to new ones. MATERIAL
AND METHODS: 25 ProTaper Next (PTN) nickel-titanium (NiTi) instruments (Maillefer
Dentsply, Baillagues, CH) for each of the following two sizes: X1 (17.04 ) and X2
(25.06) were randomly divided into two groups. The first group (n = 10)
immediately under- went to a cyclic fatigue test. The second group (n = 15) was
initially used to prepare 15 extracted molar teeth and then subjected to a cyclic
fatigue test. Same was done for 25 Horizen (HZ) instruments (Kerr Endodontics,
Orange, Ca) for each of the following two sizes: 20.04 and 25.06. Instruments
were rotated in curved artificial canal until fracture occurred and times to
fracture were recorded. All data were collected and statistically analyzed using
a variance test (confidence interval CI = 95%). RESULTS: HZ reached working
length more rapidly than PTN, and with less deformations. For the fatigue tests,
all the new instruments were significantly more resistant than the used ones. The
HZ instru- ments were significantly more resistant in all sizes than PTN, both
when new and used instruments were tested. CONCLUSIONS: Since in previous studies
ProTaper Next demonstra- ted a better resistance to cyclic fatigue than most of
nickel-titanium instruments, Horizen's performance put them in a high rank
amongst the most resistant nickel-titanium rotary instruments.
PMID- 29938740
TI - Medical Cannabis in Patients with Chronic Pain: Effect on Pain Relief, Pain
Disability, and Psychological aspects. A Prospective Non randomized Single Arm
Clinical Trial.
AB - BACKGROUND: There is an increasing interest in the medical use of cannabis,
particularly in the treatment of chronic pain. OBJECTIVES: The aim is to evaluate
the effects of cannabis use and the associated benefits reported by patients with
various chronic pain diagnoses. MATERIAL AND METHODS: A total of 338 patients
with different chro- nic pain conditions were treated with a Cannabis Flos 19%
decoction for 12 months, in addition to their pharmacological therapy. Baseline
levels for pain medications, pain intensity, pain disability, anxiety and
depression were recorded at 1, 3, 6 and 12 months. RESULTS: Pain intensity
records a statistically significant reduction from Baseline to 12 months follow
up (X2 61.375; P<0,001); the im- provements from Baseline to 12 months follow up
are also recorded in pain disability (X2 39.423; P<0,001) and in anxiety and
depression symptoms (X230.362; P<0,001; X227.786; P<0,001). CONCLUSIONS: Our
study suggest that Cannabis therapy, as an adjun- ct a traditional analgesic
therapy, can be an efficacious tool to make more effective the management of
chronic pain and its consequences on functional and psychological dimension.
Further randomized, controlled trials are needed to confirm our conclusions.
PMID- 29938741
TI - Reproductive medicine between advancement and ethics.
AB - Over the past five decades, sweeping changes have occurred in the realm of
childbirth. Thanks to medically assisted procreation, child- birth as an event
has come to be characterized by the interweaving of biological as well as social
elements. Research has been forging ahead, the first uterus transplant has been
carried out and the experimental cloning of apes has taken place in China. All
such innovations entail a wide array of ethical and medical issues, involving
different parties in the process of generating new life: parents, children and
gamete donors.
PMID- 29938742
TI - Continuous non-invasive measurement of stroke volume and cardiac index in infants
and children: comparison of Impedance Cardiography NICaS(r) vs CardioQ(r) method.
AB - BACKGROUND: Non-invasive measurement of cardiac output (CO) and cardiac index
(CI) may become an important modality of moni- toring in pediatrics. Among the
several methods proposed, impedance cardiography (ICG) has gained attention among
the scientists. There are 2 basic technologies of ICG: thoracic body bioimpedance
(TEB) and whole body electrical bioimpedance (WBEB). PURPOSE: The present study
is aimed to test in infants and children the effectiveness of the Non-Invasive
Cardiac System (NICaS(r)), a new ICG device working with a wrist-to-ankle
configuration vs Car- dioQ(r) transesophageal doppler, a minimally invasive
cardiac output monitor. METHODS: Whole-body bioimpedance measurements were
obtained before and during the surgery with NICaS(r) and simultaneously with
CardioQ(r), demographic data were sampled, basement life monitoring were
performed. RESULTS: Total of 42 patients aged from new born to 16 years old, were
included in this study to evaluate heart rate (HR), stroke volume (SV), cardiac
output (CO), cardiac index (CI), total peripheral resi- stance index (TPRI),
total body water (TBW) and cardiac power index (CPI). 81 measurements were taken
simultaneously by both devices from forty-two patients, with CardioQ(r) serving
as the gold-standard for this evaluation and with NICaS(r). The average values of
CI in the study subjects for CardioQ(r) cardiac index (Q-CI) and NICaS(r) cardiac
index (NI-CI) were 2.9+/-0.9 L/min/m2 and 2.8+/-1.0 L/min/m2 respecti- vely
(P<0.01). Overall, 2-tailed Pearson's correlation between NI-CI and Q-CI was r =
0.85. The Bland-Altman 1.96-standard deviation limit of agreement was -0.77 L/min
and 0.87 L/min/m2 with a small bias of 0.05 L/min/m2. CONCLUSIONS: Good
correlation was observed in pediatric patients for CI measured with NICaS(r) in
comparison with CardioQ(r) device. Continuous non-invasive monitoring of NI-CI
can be particularly in- teresting for the pediatric population.
PMID- 29938743
TI - Stress at work: development of the Stress Perception Questionnaire of Rome
(SPQR), an ad hoc questionnaire for multidimensional assessment of work related
stress.
AB - Stress is an emotional condition, mostly experienced as negative, initially
identified and defined by Selye in the mid-thirties of the last Century. Since
the first definition, stress concerns the adaptation pro- cess mostly related to
environmental changes. An application of stress focuses on the evaluation of its
interference on work conditions, and the scientific evidence on work related
stress is very ample and rich. We are proposing a new ad hoc questionnaire for
the multidimensional assessment of work related stress, called Stress Perception
Question- naire of Rome (SPQR) composed of 50 items. The development of this
questionnaire is based on a multi-step process: a) Identification of all the
relevant topics to work related stress and areas in the scientific evidence and
their transformation on specific contents of 60 tentative items; b) Exploratory
factor analysis aimed to identify the best items (50) which could guarantee the
maximum convergence on single scales (8), and the minimum redundancy between
scales; c) Validation of the 8 scales' structure by a confirmatory factor
analysis (fully achieved); d) Factor analysis for a second level factor resulting
in a single factor identified as the questionnaire total score (Stress Score); d)
Reliability analysis of the questionnaire total score and the single scale scores
(at optimum level); e) Validation by external criteria of work related stress
identified in the presence of personal violence episodes experienced by a group
of health workers with different professional profiles and from two different
hospitals in Rome. Our results show that the SPQR is a useful and sensitive tool
for assessing the presence of emotional stress related problems identifiable in a
work environment. The advantage of this questionnaire is that it allows for a
multidimensional description of the different components of this problematic area
besides its ability to quantify the overall stress level of those who have been
administered the SPQR.
PMID- 29938744
TI - Errors in Medicine: perception of healthcare professionals in the Lazio Region.
AB - INTRODUCTION: The error in medicine is always the subject of debate in the
scientific debates. The purpose of this study is to evaluate the degree
knowledge, attitudes and behaviors of health workers towards the error in the
health sector. METHODS: A survey was carried out involving 435 health profes-
sionals working in health facilities of the Lazio region, of which 312 females
(71%) and 123 males (28%) with an age between 21 and 68 years. A structured
questionnaire was administered for investigating the experiences and opinions
about the errors found in medical prac- tice, the causes underlying them and the
mistakes that should never be committed. Data were collected, stratified by sex,
age, marital status, year of graduation, years of service and the workplace
(medical or surgical). The statistical significance was set at p<=0.05. RESULTS:
The 5 errors found more frequently in the clinical prac- tice by health
professionals were as follows: errors related to the request for examination
(60.9%); errors in the collection of samples (37.5%); errors relating to the
delivery of the reports (35.2%); errors due to reporting of examinations (31.7%);
errors of history (29.2%). The five cases considered to be the most frequently
responsible for such errors were: disorganization (52%); fast (46.4%); tiredness
due to excessive workloads, stress (44.6%); negligence and carelessness (41.6%);
inattention (41.1). With regard to the errors that you should never commit they
were more frequently: exchange of patient or misidentification of the patient
(49.2%); administration errors of therapies or medications (47.6%); errors
related to surgery (41.6%); errors of prescription therapies or medications
(39.3); errors in the reporting of exams (33.6%). CONCLUSIONS: The results of
this study shows the importance of a culture of error in medicine among
healthcare professionals, those who have already gained practical experience in
health care and therefore better able to perform a critical analysis and
evaluation of the errors that occur every day. The continuous training of health
professionals is fundamental for promoting patient safety and quality in the
healthcare sector.
PMID- 29938745
TI - Munchausen Syndrome by Proxy: balancing ethical and clinical challenges for
healthcare professionals Ethical consideration in factitious disorders.
AB - Munchausen syndrome by proxy is a relatively rare behavioral disorder affecting a
child's primary caregiver, typically the mother. Ethical dilemmas that physicians
may face in such situations mainly concern the medical options for best
protecting the child's welfare, that are important, in clinical pediatric
practice, because critical conflicts might arise between health professionals and
parents. In such cases, the physician's primary obligation is to protect the
children involved, whose family environment may be essential to their wellbeing.
Ev- ery ethical choice should be tailored to a given child's story, which should
be viewed as a whole, considering the possible consequences for the family
balance, and taking the complexity of the emotional and psychological dimensions
of children's relationship with their parents into account. Specific protocols,
discussion of clinical cases, open communi- cation of feelings will help doctors
to deal more effectively with the families involved and ensure that treatment
decisions are made in the child's best interest.
PMID- 29938746
TI - The missing link between philosophy and psychopathology.
AB - INTRODUCTION: The uncertainty regarding the scientific status of psychiatry
arises from psychiatry's involvement with some unsolved problems, or put in
another way, from its enmeshment in certain points of transition of contemporary
science. There is, in primis, the unsolved problem of the relationship between
the mind and the body and, moreo- ver, the intricate relationship of
connection/disjunction among biology, social science, anthropology, philosophy,
etc. To speak about what psychopathology can expect from philosophy is, above
all, to immerse oneself in a debate about the conditions of possibility of
psychiatry as a science. This debate is especially concerned with the models of
knowledge that have, until now, been proposed to psychiatry. Those models
oscillate between the Dilthey's paradigms of the "Science of Nature" and the
"Science of Spirit". METHODS: It is certain that psychopathology, as already
indicated by Jaspers, is a discipline which is among the most involved regard-
ing the use of the two different cognitive strategies. The first strategy
concerns the concept of "explanation" and its rigid approach to the objective and
ultimate cause of the phenomenon. The second strategy is the "comprehensive"
approach. This model, which the hermeneutic thought defines "interpretative",
theorizes the provisional character, the subjectiveness and the finiteness of
every cognitive project. RESULTS: The interest of the authors is orientated
towards the hermeneutic side (comprehensive-interpretative) of psychiatry, that
which deals with the specificity of every clinical history, with the continuity
of sense, and with intrinsic narrative intelligibility of every human event,
psychopathological or not. CONCLUSIONS: This approach to psychopathology is based
on the statement: "a clinical history is a text which must be interpreted". From
this perspective, every clinical history should be perceived as a text to
decipher but, above all, as a "text" to listen to, in the persevering expectation
that it could disclose its particular "project of world". When speaking about
psychiatry, we always face a problem which dominates all the others: the unsolved
problem of the relation- ship between typicalness and singularity of subjective
events. B.B. Mandelbrot, theorist of "fractals", sums this dilemma up clearly. He
suggests that the innumerable variety of the configurations of Nature is a
challenge to investigate the morphology of that which is "irregu- lar" in order
to discover in it, as far as possible, a rule.
PMID- 29938747
TI - Models to crack the code of organ regeneration.
AB - In recent years, there has been a growing, widespread interest in tissue
regeneration, with all its medical and social implications, such as, for example,
the recovery from illness and wellbeing of humans. Yet, some of the most
noticeable features of regeneration were discovered using a purely biological
perspective with experimental biology on animal models. We are proud to introduce
this Special Issue of The International Journal of Developmental Biology (Int. J.
Dev. Biol.) on Regeneration Biology, which is devoted to the different animal
models currently used to study regeneration. We also have tailored this Special
Issue to include the different achievements that are today the state-of-the art
in tissue and organ regeneration. The animal model perspective allows us to
identify common and specific traits, summarize the most relevant advances,
establish knowledge for the new "kids-on-the-block" and provide a framework to
explore the open questions that researchers in the field are pursuing.
PMID- 29938748
TI - Regeneration: sooner rather than later.
AB - The explosive growth of information from genetics and genomics has led to an
appreciation of the conservation of gene regulatory networks between organisms,
and between development and regeneration. With ever increasing knowledge, it will
be possible to intervene therapeutically to regulate these networks, which will
lead to new therapies to induce regeneration. The question then becomes how to do
this, rather then when to try. Our thesis is that the time is now, and that this
feat can be achieved by combining the insights provided by developmental
biologists with the technologies being developed by biomaterial engineers, to
achieve the goal of engineering regeneration. We thus envision regenerative
engineering as the next step toward achieving the goal of human regeneration.
Among the most important discoveries about regeneration from studies of
salamanders that regenerate exceptionally well, is that both pattern-following
and pattern-forming cells are required. Much progress is being made toward
understanding the former cells, but little is known about the cells that control
positional information and pattern formation. Within the near future, it will
become possible to provide the information needed for regeneration exogenously in
the form of an engineered extracellular matrix that is a biomimetic of the
endogenous information. Since growth factors (morphogens) can control pattern
formation, an engineered grid could be based on spatially organized patterns of
sulfation of glycosaminoglycans that control the behavior of cells by modulating
morphogen activity. Progress in engineering the positional information grid for
regeneration will necessitate learning the sulfation codes associated with
successful regeneration in animals such as salamanders.
PMID- 29938749
TI - The evolution of regeneration - where does that leave mammals?
AB - This brief review considers the question of why some animals can regenerate and
others cannot and elaborates the opposing views that have been expressed in the
past on this topic, namely that regeneration is adaptive and has been gained or
that it is a fundamental property of all organisms and has been lost. There is
little empirical evidence to support either view, but some of the best comes from
recent phylogenetic analyses of regenerative ability in Planarians which reveals
that this property has been lost and gained several times in this group. In
addition, a non-regenerating species has been induced to regenerate by altering
only one signaling pathway. Extrapolating this to mammals it may be the case that
there is more regenerative ability in mammals than has typically been thought to
exist and that inducing regeneration in humans may not be as impossible as it may
seem. The regenerative abilities of mammals is described and it turns out that
there are several examples of classical epimorphic regeneration involving a
blastema as exemplified by the regenerating Urodele limb that can be seen in
mammals. Even the heart can regenerate in mammals which has long been considered
to be a property unique to Urodeles and fish and several recent examples of
regeneration have come from recent studies of the spiny mouse, Acomys, which are
discussed here. It is suggested that a much more thorough phylogenetic analysis
of mammalian regeneration would likely reveal some important insights into the
evolution of regeneration.
PMID- 29938750
TI - Non-developmental dimensions of adult regeneration in Hydra.
AB - An essential dimension of 3D regeneration in adult animals is developmental, with
the formation of organizers from somatic tissues. These organizers produce
signals that recruit surrounding cells and drive the restoration of the missing
structures (organs, appendages, body parts). However, even in animals with a high
regenerative potential, this developmental potential is not sufficient to achieve
regeneration as homeostatic conditions at the time of injury need to be "pro
regenerative". In Hydra, we identified four distinct homeostatic properties that
provide a pro-regenerative framework and we discuss here how these non
developmental properties impact regeneration. First, both the epithelial and the
interstitial-derived cells are highly plastic along the animal body, a plasticity
that offers several routes to achieve regeneration. Second, the abundant stocks
of continuously self-renewing adult stem cells form a constitutive pro-blastema
in the central body column, readily activated upon bisection. Third, the
autophagy machinery in epithelial cells guarantees a high level of fitness and
adaptation to detrimental environmental conditions, as evidenced by the loss of
regeneration in animals where autophagy is dysfunctional. Fourth, the
extracellular matrix, named mesoglea in Hydra, provides a dynamically-patterned
environment where the molecular and mechanical signals induced by injury get
translated into a regenerative process. We claim that these homeostatic pro
regenerative features contribute to define the high regenerative potential of
adult Hydra.
PMID- 29938751
TI - Can broken hearts be mended? Ken Poss, a pioneer on heart regeneration research.
AB - In 2002, Ken Poss discovered that zebrafish, at that time an emerging vertebrate
model organism in basic research, were able to regenerate their heart upon
resection of the ventricular apex. This finding set in motion a new field of
research on heart regeneration, which has recently expanded in other model
organisms including mammals. We interviewed Ken Poss to find out more about his
motivation and vision for the future of tissue regeneration research.
PMID- 29938752
TI - Elly Tanaka's passion for exploring animal regeneration.
AB - This interview, performed by the guest editors of this Int. J. Dev. Biol. Special
Issue on Regeneration, narrates the story of Elly M. Tanaka on her regeneration
research journey. The main goal is to get a glimpse of the thoughts and
scientific history of this leading figure in regeneration biology. In addition to
her scientific history, we will learn about her captivating determination to ask
relevant questions in science and her use of animal models for solving complex
problems.
PMID- 29938753
TI - Role of the immune response in initiating central nervous system regeneration in
vertebrates: learning from the fish.
AB - The mammalian central nervous system is not able to regenerate neurons lost upon
injury. In contrast, anamniote vertebrates show a remarkable regenerative
capacity and are able to replace damaged cells and restore function. Recent
studies have shown that in naturally regenerating vertebrates, such as zebrafish,
inflammation is a key processes required for the initiation of regeneration.
These findings are in contrast to many studies in mammals, where the central
nervous system has long been viewed as an immune-privileged organ with
inflammation considered one of the key negative factors causing lack of neuronal
regeneration. In this review, we discuss similarities and differences between
naturally regenerating vertebrates, and those with very limited to non-existing
regenerative capacity. We will introduce neural stem and progenitor cells in
different species and explain how they differ in their reaction to acute injury
of the central nervous system. Next, we illustrate how different organisms
respond to injuries by activation of their immune system. Important immune cell
types will be discussed in relation to their effects on neural stem cell
behavior. Finally, we will give an overview on key inflammatory mediators
secreted upon injury that have been linked to activation of neural stem cells and
regeneration. Overall, understanding how species with regenerative potential
couple inflammation and successful regeneration will help to identify potential
targets to stimulate proliferation of neural stem cells and subsequent
neurogenesis in mammals and may provide targets for therapeutic intervention
strategies for neurodegenerative diseases.
PMID- 29938754
TI - Kidney regeneration in fish.
AB - Age-related diseases, such as kidney diseases, are becoming more prevalent in
aging societies. Currently, patients with reduced kidney function require
dialysis or organ transplants. Those who suffer from kidney disease would benefit
from regenerative therapies. Thus, one of the ultimate goals of regeneration
research is to enhance an individual's capacity of self-repairing damaged tissue;
something that fish models can contribute towards. Kidney structures are
conserved among vertebrates highlighting the opportunities for fish to act as
human disease models. Here, different species can offer respective advantages. An
understanding of the different modes of regeneration can help to visualize the
differences in mammalian and fish regenerative capacity. The remarkable
regenerative capacity of fish is well known, but kidney regeneration is an
understudied area. The kinetics of kidney regeneration allows one to investigate
early damage responses, as well as the initiation and completion of repair. Age
related reductions in regeneration are an additional societal problem; again an
area where fish models can be of help. Age-matched experiments between varied
vertebrate species will help us to learn from those that do or do not exhibit age
related phenotypes. The goal of such experiments is not only to outline important
age-related factors and pathways, but, in addition, to see if age-related
decreases in regenerative capacity can be reduced. Widening our knowledge of this
very complex process will help to address many of the unanswered questions in the
field.
PMID- 29938755
TI - Plasticity of human adipose-derived stem cells - relevance to tissue repair.
AB - In contrast to cold blooded vertebrates, the ability to regenerate
morphologically and functionally complex structures is limited in adult mammals.
Recruitment of progenitor cells is a key step in the regenerative process. The
possibility of repairing missing or diseased tissues in humans has been
potentiated by the increasing understanding of somatic stem cells, their
plasticity and the possibility of modulating it, that could be harnessed either
to stimulate endogenous repair or to engineer the required tissue. Here, we focus
on human mesenchymal stem cells (MSCs), important players in tissue homeostasis
in healthy organisms, with a particular emphasis on those derived from the
adipose tissue (ADSCs). While a mark of MSC identity is the ability to
differentiate into osteoblasts, chondrocytes and adipocytes, there is evidence
that their potential goes beyond these three mesenchymal lineages. We discuss
some differentiation and modulatory properties of MSCs and provide an overview of
our recent work on ADSCs from paediatric patients (pADSCs) that has shown their
ability to give raise to non-mesenchymal cells, consistent with a significant
plasticity. Finally, we present novel data indicating that both mesenchymal
lineages (adipogenic, chondrogenic and osteogenic) and neural and epithelial
lineages can originate from clonal lines that like the parental line express
markers of pluripotency as well as the stromal cell marker, GREM1. Together these
data support the existence of pADSC multipotent stem cells.
PMID- 29938756
TI - Revisiting the liver: from development to regeneration - what we ought to know!
AB - The liver is structurally and functionally heterogeneous and complex, and it
accomplishes crucial functions for the organism. Its most remarkable potential is
its capacity to regenerate after injury in order to maintain whole body
homeostasis and guarantee the survival of the individual. Under normal
conditions, liver regeneration (LR) is attributed to adult hepatocytes, the main
cells in the liver which are able to proliferate in response to different stimuli
or injuries. Nevertheless, when liver injury is severe and/or hepatocytes are
prevented from proliferation, liver stem/progenitor cells (LS/PCs) participate
directing LR to maintain liver mass and functions. Different mechanisms have been
shown to guide this second line of LR, such as intrahepatic and extrahepatic
liver progenitor cells, as well as transdifferentiation processes between
hepatocytes and other liver cells. For this reason, many efforts have been made
to elucidate the specific molecular mechanisms which orchestrate this process;
this in turn would improve the prognosis and treatment of liver diseases. In this
review, we revisit the fascinating process of LR, also with a short overview
about liver development, the process from which arises the concept of LS/PCs
participating in LR, and very important nowadays when considering cell therapy
and tissue bioengineering for the treatment of patients suffering from liver
disease.
PMID- 29938757
TI - The triumvirate of beta-cell regeneration: solutions and bottlenecks to curing
diabetes.
AB - On 11 January 1922 insulin injection was used for the first time in the treatment
of diabetes. Even today, daily insulin injections are the life-saving treatment
for patients with Type 1 diabetes and advanced Type 2 diabetes. However, insulin
injections often fail to achieve full glucose control, which in the long-term
leads to multiple complications and mortality. Beta-cells, the natural producers
and secretors of insulin, remain the gold-standard in regulating blood glucose
levels. In this review, we focus on three strategies aiming at counteracting beta
cell loss in order to gain insulin independence: replacement, replication and
protection. The three approaches, together termed as the triumvirate of beta-cell
regeneration, may constitute the basis for a future cure for diabetes.
PMID- 29938758
TI - Reservoirs for repair? Damage-responsive stem cells and adult tissue regeneration
in Drosophila.
AB - Adult stem cells in mammals are important for normal tissue renewal (homeostasis)
and regeneration after injury. In the past ten years, different types of
homeostatic adult stem cells have also been identified in the genetically
accessible fruit fly (Drosophila melanogaster), among which intestinal stem cells
have taken centre stage. Recent studies provide evidence that adult fly tissues
may also harbor quiescent stem cells, which can enter cell cycle upon injury to
regenerate compromised tissue. Such damage-responsive stem cells have been
described in flight muscles, the adult brain and in a narrow region of the fly
hindgut. Strikingly, many mammalian tissues have also been shown to maintain
quiescent, but regeneration-competent, stem cells. However, little is known about
the injury-induced signals that lead to their activation. Here, we provide a
brief overview of active and damage-responsive adult stem cells in the fruit fly
and focus on injury-dependent signalling events. We highlight the potential of
Drosophila to model damage-induced stem cell activation to deepen our molecular
understanding of how dormant stem cells can be efficiently recruited for tissue
repair after injury.
PMID- 29938759
TI - Linking wound response and inflammation to regeneration in the zebrafish larval
fin.
AB - The study of regenerative biology aims to elucidate the innate ability of
organisms to replace tissues or organs after they have been removed or damaged.
The zebrafish is a powerful model for the analysis of intracellular signalling
and cell behaviour and as such has made major contributions to our understanding
of regenerative biology. The larval fin fold is an emerging model to understand
how different signalling pathways interact to coordinate regeneration. Tissue
damage causes the immediate release of signals that initiate wound closure and
inflammation. Following this, regenerative cells proliferate and migrate to the
damaged area. Each of these processes has been analysed using the larval fin fold
model to provide a framework for how fin regeneration takes place. This review
gives an overview of the current state of this field with particular emphasis on
the different signalling networks that are required during fin fold regeneration.
PMID- 29938760
TI - Crawling wounded: molecular genetic insights into wound healing from Drosophila
larvae.
AB - For animals, injury is inevitable. Because of this, organisms possess efficient
wound healing mechanisms that can repair damaged tissues. However, the molecular
and genetic mechanisms by which epidermal repair is accomplished remain poorly
defined. Drosophila has become a valuable model to study epidermal wound healing
because of the comprehensive genetic toolkit available in this organism and the
similarities of wound healing processes between Drosophila and vertebrates. Other
reviews in this Special Issue cover wound healing assays and pathways in
Drosophila embryos, pupae and adults, as well as regenerative processes that
occur in tissues such as imaginal discs and the gut. In this review, we will
focus on the molecular/genetic control of wound-induced cellular processes such
as inflammation, cell migration and epithelial cell-cell fusion in Drosophila
larvae. We will give a brief overview of the three wounding assays, pinch,
puncture, and laser ablation, and the cellular responses that ensue following
wounding. We will highlight the actin regulators, signaling pathways and
transcriptional mediators found so far to be involved in larval epidermal wound
closure and what is known about how they act. We will also discuss wound-induced
epidermal cell-cell fusion and possible directions for future research in this
exciting system.
PMID- 29938762
TI - Regenerative response of different regions of Drosophila imaginal discs.
AB - Thanks to the introduction of new methods to induce massive damage under
controlled conditions, much information about regeneration in Drosophila imaginal
discs has accumulated in recent years. In this review, we discuss results
concerning primarily the wing disc, putting emphasis on the different
regenerative responses of the wing appendage, which exhibits a robust
regenerative potential, and the trunk region, the notum, which regenerates very
poorly. The wing disc may be a paradigm of a tissue in which a common original
lineage generates cells with distinct regenerative potential. We argue that a key
factor in those differences is the activity of the Jun N-terminal Kinase (JNK)
pathway, which functions differently in the appendage and the body trunk.
PMID- 29938763
TI - The cellular and molecular bases of the sponge stem cell systems underlying
reproduction, homeostasis and regeneration.
AB - The evolution of multicellular organisms is generally thought (and seems likely)
to have been accompanied by the evolution of a stem cell system. Sponges, some of
the early-evolved metazoans, have totipotent/pluripotent stem cells. Thus,
uncovering the cellular and molecular bases of the sponge stem cells will not
only be crucial for understanding the ancestral gene repertoire of animal stem
cells, but will also give us clues to understanding the evolution of molecular
mechanisms for maintaining multipotency (pluripotency) and differentiation
ability during animal evolution. Sponges (Porifera) are a large phylum that
includes an enormous number of species, whose cellular compositions and life
cycles show striking variations. In the last decade, methodologies for molecular
studies and sequencing resources have dramatically advanced and made it possible
to clearly define stem cells in sponges in cellular and molecular terms. In this
review, together with recent studies of sponges in various classes, the following
issues will be discussed: i) recent findings that revealed that the previously
proposed model that "archeocytes and choanocytes are the two types of stem cells"
originally based on work in demosponges can be applied as a unified view of the
stem cell system in sponges that have various cellular organizations, ii) the
fact that sponge cells are more plastic than previously thought, as shown by
recent studies of sponge regeneration both from dissociated cells and upon
injury, and iii) the importance of transdifferentiation in sponge stem cell
systems and regeneration.
PMID- 29938764
TI - Myths vs. FACS: what do we know about planarian stem cell lineages?
AB - Historically, planarian neoblasts were thought to be a homogeneous population of
pluripotent stem cells; however, recent population and single-cell level analyses
have refuted this idea. Evidence for lineage commitment at the neoblast level has
been provided via a number of independent studies using a variety of methods. In
situ hybridization experiments first demonstrated the co-expression of lineage
specific markers in neoblasts (marked by piwi-1 expression) isolated by FACS.
Subsequently, single cell transcriptomic analyses of FACS-isolated neoblasts
uncovered broad lineage-primed neoblast classes based on the clustering of
transcriptional profiles and expression of known tissue-specific markers.
Additionally, single neoblast pluripotency (and fate restriction) has been
demonstrated by single cell transplantation experiments into neoblast-void
animals. Here we look to recount the current status of the planarian neoblast
field and offer discussion on the caveats of neoblast biology and how to address
them experimentally.
PMID- 29938765
TI - Rebuilding a planarian: from early signaling to final shape.
AB - Why some animals can regenerate and others not has fascinated biologists since
the first examples of regeneration were reported. Although many animal phyla
include species with some regenerative ability, mainly restricted to particular
cell types or tissues, there are some other species capable of regenerating
complex structures, such as the vertebrate limb and heart. More remarkably, there
are some examples of animals that can regenerate the whole body from a tiny piece
of them. Understanding how regeneration is triggered and achieved in these
animals is fundamental not only to understand this fascinating primary biological
question, but also because of its implications for the field of regenerative
medicine. Here, we discuss one of the models with higher regenerative
capabilities: the freshwater planarians. Two key features make planarians an
attractive model to study regeneration: the presence of adult pluripotent stem
cells and the permanent activation of the morphogenetic mechanisms that instruct
cell fate. Here, we revise our current knowledge of key events that lead to
successful regeneration including: how heterogeneous is the stem cell population;
what are the immediate changes at the gene level after amputation and what
triggers the regenerative response; how is axial polarity re-established; how do
the different cell types differentiate from lineage-committed progenitors and how
is size and organ proportionality controlled. Finally, we point out some open
questions that the field needs to address in the near future.
PMID- 29938761
TI - Wound healing, cellular regeneration and plasticity: the elegans way.
AB - Regeneration and wound healing are complex processes that allow organs and
tissues to regain their integrity and functionality after injury. Wound healing,
a key property of epithelia, involves tissue closure that in some cases leads to
scar formation. Regeneration, a process rather limited in mammals, is the
capacity to regrow (parts of) an organ or a tissue, after damage or amputation.
What are the properties of organs and the features of tissue permitting
functional regrowth and repair? What are the cellular and molecular mechanisms
underlying these processes? These questions are crucial both in fundamental and
applied contexts, with important medical implications. The mechanisms and cells
underlying tissue repair have thus been the focus of intense investigation. The
last decades have seen rapid progress in the domain and new models emerging.
Here, we review the fundamental advances and the perspectives that the use of C.
elegans as a model have brought to the mechanisms of wound healing and cellular
plasticity, axon regeneration and transdifferentiation in vivo.
PMID- 29938766
TI - The regenerative flatworm Macrostomum lignano, a model organism with high
experimental potential.
AB - Understanding the process of regeneration has been one of the longstanding
scientific aims, from a fundamental biological perspective, as well as within the
applied context of regenerative medicine. Because regeneration competence varies
greatly between organisms, it is essential to investigate different experimental
animals. The free-living marine flatworm Macrostomum lignano is a rising model
organism for this type of research, and its power stems from a unique set of
biological properties combined with amenability to experimental manipulation. The
biological properties of interest include production of single-cell fertilized
eggs, a transparent body, small size, short generation time, ease of culture, the
presence of a pluripotent stem cell population, and a large regeneration
competence. These features sparked the development of molecular tools and
resources for this animal, including high-quality genome and transcriptome
assemblies, gene knockdown, in situ hybridization, and transgenesis. Importantly,
M. lignano is currently the only flatworm species for which transgenesis methods
are established. This review summarizes biological features of M. lignano and
recent technological advances towards experimentation with this animal. In
addition, we discuss the experimental potential of this model organism for
different research questions related to regeneration and stem cell biology.
PMID- 29938767
TI - Molecular mechanisms of limb regeneration: insights from regenerating legs of the
cricket Gryllus bimaculatus.
AB - This review summarizes recent advances in leg regeneration research, focusing on
the cricket Gryllus bimaculatus. Recent studies have revealed molecular
mechanisms on blastema formation, establishment of positional information, and
epigenetic regulation during leg regeneration. Especially, these studies have
provided molecular bases in classical conceptual models such as the polar
coordinate model, the intercalation model, the boundary model, the steepness
model, etc., which were proposed to interpret regeneration processes of the
cockroach legs. When a leg is amputated, a blastema is formed through the
activation of the Janus-kinase (Jak)/Signal-Transduction-and-Activator-of
Transcription (STAT) pathway. Subsequently, the
Hedgehog/Wingless/Decapentaplegic/Epidermal-growth-factor pathways instruct
distalization in the blastema, designated as the molecular boundary model.
Downstream targets of this pathway are transcription factors Distal-less (Dll)
and dachshund (dac), functioning as key regulators of proximodistal pattern
formation. Dll and dac specify the distal and proximal regions in the blastema,
respectively, through the regulation of tarsal patterning genes. The expression
of leg patterning genes during regeneration may be epigenetically controlled by
histone H3K27 methylation via Enhancer-of-zeste and Ubiquitously-transcribed
tetratricopeptide-repeat-gene-X-chromosome. For the molecular mechanism of
intercalation of the missing structures between the amputated position and the
most distal one, Dachsous/Fat (Ds/Ft) steepness model has been proposed, in which
the Ds/Ft pathway maintains positional information and determines leg size
through dac expression. This model was theoretically verified to interpret the
experimental results obtained with cricket legs. Availability of whole-genome
sequence information, regeneration-dependent RNA interference, and genome editing
technique will have the cricket be an ideal model system to reveal gene functions
in leg regeneration.
PMID- 29938769
TI - New mechanisms driving muscle stem cell regenerative decline with aging.
AB - Stem cells must preserve their function in order to sustain organ and tissue
formation, homeostasis and repair. Adult stem cells, particularly those resident
in tissues with little turnover, remain quiescent for most of their life,
activating only in response to regenerative demands. Among the best studied long
lived quiescent stem cells are skeletal muscle stem cells, which are fully
equipped to sustain repair in response to tissue trauma. Recent evidence
indicates that the preservation of muscle stem-cell quiescence and regenerative
capacity depends on intracellular networks linking metabolism and protein
homeostasis. Here, we review recent research into how these networks control stem
cell function and how their dysregulation contributes to aging, with a particular
focus on senescence entry in extreme old age. We also discuss the implications of
these new findings for anti-aging research in muscle stem-cell-based regenerative
medicine.
PMID- 29938770
TI - Cellular senescence in tissue repair: every cloud has a silver lining.
AB - Cellular senescence, a form of stable cell cycle arrest induced by cellular
stress, constitutes a major factor leading to the promotion of pathologies and
physiological decays that take place during ageing. However, in recent years
evidence has started to emerge supporting a positive role for senescent cells in
various physiological processes, from embryonic development to tissue injury
responses such as wound healing and tissue repair. Here, we provide an overview
of cellular senescence, its negative as well as positive outcomes, with a focus
on its impact on tissue repair. Furthermore, we discuss the possibility that cell
senescence could contribute to the regeneration of complex structures and explore
recent findings with respect to their potential for therapeutic application.
PMID- 29938768
TI - Homeostasis, regeneration and tumour formation in the mammalian epidermis.
AB - The epidermis is the outer covering of the skin and provides a protective
interface between the body and the environment. It is well established that the
epidermis is maintained by stem cells that self-renew and generate differentiated
cells. In this review, we discuss how recent technological advances, including
single cell transcriptomics and in vivo imaging, have provided new insights into
the nature and plasticity of the stem cell compartment and the differing roles of
stem cells in homeostasis, wound repair and cancer.
PMID- 29938771
TI - Elevated serum interleukin-29 levels in patients with Henoch-Schonlein purpura.
PMID- 29938773
TI - Assessment of skin temperature during regional anaesthesia-What the
anaesthesiologist should know.
AB - Body temperature homeostasis is accurately regulated by complex feedback-driven
neuronal mechanisms, which involve a multitude of thermoregulatory pathways.
Thus, core temperature is constantly maintained within a narrow range. As one of
the most effective regulatory systems skin temperature is dependent on skin blood
flow. Skin blood flow in turn is highly dependent on sympathetic activity.
Regional anaesthesia leads to blockade not only of somatosensory and motor nerve
fibres but also of sympathetic fibres. As a consequence, vasoconstrictor tonic
activity is abrogated and a vasodilation leads to an increase in skin blood flow
and temperature. The aim of this review was to summarize the general physiology
of thermoregulation and skin temperature as well as the alterations during
regional anaesthesia. The main focus was the usefulness of measuring skin
temperature as an indicator of regional anaesthesia success. According to the
available literature, assessment of skin temperature can indeed serve to predict
success of regional anaesthesia. Hence, it is important to realize that relevant
and reliable temperature increase is only seen in the most distal body parts, ie
fingers and toes. More proximally, temperature changes are frequently small and
inconsistent, which means that assessment of block levels is not possible by
temperature measurement. Furthermore, relevant skin temperature increases will
only be observed in patients, which are initially vasoconstricted. In conclusion,
measurement of skin temperature represents a reliable and feasible diagnostic
tool to assess and predict the success or failure of regional anaesthesia
procedures, especially in patients in which sensory testing is impossible.
PMID- 29938772
TI - Twice-weekly ixazomib in combination with lenalidomide-dexamethasone in patients
with newly diagnosed multiple myeloma.
AB - Weekly ixazomib with lenalidomide-dexamethasone (Rd) is feasible and has shown
activity in newly diagnosed multiple myeloma (NDMM) patients. This phase 1/2
study (NCT01383928) evaluated the recommended phase 2 dose (RP2D),
pharmacokinetics, safety and efficacy of twice-weekly ixazomib plus Rd in NDMM;
64 patients were enrolled across both phases. Patients received twice-weekly oral
ixazomib 3.0 or 3.7 mg plus lenalidomide 25 mg and dexamethasone 20 mg (10 mg in
cycles 9-16) for up to sixteen 21-day cycles, followed by maintenance with twice
weekly ixazomib alone. No dose-limiting toxicities were reported in cycle 1; the
RP2D was 3.0 mg based on overall tolerability across multiple cycles. In 62
evaluable patients, the confirmed overall response rate was 94% (68% >=very good
partial response; 24% complete response). Median progression-free survival was
24.9 months. Responses (median duration 36.9 months for patients receiving the
RP2D) deepened during treatment. Grade 3 drug-related adverse events (AEs)
occurred in 64% of patients, including: rash, 13%; peripheral neuropathy, 8%;
hyperglycaemia, 8%. There were no grade 4 drug-related AEs. Thirteen patients
discontinued due to AEs. Twice-weekly ixazomib-Rd offers substantial activity
with promising long-term outcomes in NDMM patients but may be associated with
greater toxicity compared with weekly ixazomib-Rd in this setting.
PMID- 29938774
TI - Daratumumab proves safe and highly effective in AL amyloidosis.
PMID- 29938775
TI - Expression profile of the amino acid transporters SLC7A5, SLC7A7, SLC7A8 and the
enzyme TDO2 in basal cell carcinoma.
AB - BACKGROUND: The incidence of basal cell carcinoma (BCC) is increasing and the
costs for care rising. Therefore, the need for simplified and cost-effective
treatment choices is substantial. Aberrant signalling in several pathways,
induced by ultraviolet radiation, is of importance in the development of BCC.
Alterations in tumour metabolic activity are part of general carcinogenesis;
however, these alterations are only partially recognized in skin cancer.
OBJECTIVES: To study expression profiles in BCCs compared with individually
matched nontumour skin, with a focus on finding differences associated with
tumour metabolism. MATERIALS AND METHODS: Gene expression in biopsies from BCCs
(n = 14) compared with biopsies from nontumour gluteal skin was analysed with
microarrays (n = 4 + 4) and/or quantitative real-time polymerase chain reaction
(qPCR, n = 14 + 14). Protein expression and localization was assessed using
immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded BCC samples.
RESULTS: Microarray analysis revealed increased expression of the amino acid
transporters SLC7A5, SLC7A7 and SLC7A8 as well as the cytosolic enzyme tryptophan
2,3-dioxygenase (TDO) 2 in BCC. Higher expression of SLC7A5 (P < 0.001), SLC7A8
(P < 0.001) and TDO2 (P = 0.002), but not SLC7A7 (P = 0.50), was confirmed by
qPCR, and IHC demonstrated correlating tumour cell protein expression of SLC7A5
and SLC7A8. Protein expression of SLC7A7 was observed in the stratum granulosum,
and TDO2 in immune cells. CONCLUSIONS: This study highlights the upregulation of
SLC7A5, SLC7A8 and TDO2 in BCC compared with nontumour skin. Our findings imply
that amino acid transporters may be further explored as potential targets for
future medical treatment.
PMID- 29938776
TI - Meta-analytic findings reveal lower means but higher variances in visuospatial
ability in dyslexia.
AB - Conflicting empirical and theoretical accounts suggest that dyslexia is
associated with either average, enhanced, or impoverished high-level visuospatial
processing relative to controls. Such heterogeneous results could be due to the
presence of wider variability in dyslexic samples, which is unlikely to be
identified at the single study level, due to lack of power. To address this, this
study reports a meta-analysis of means and variances in high-level visuospatial
ability in 909 non-dyslexic and 956 dyslexic individuals. The findings suggest
that dyslexia is associated not only with a lower mean performance on
visuospatial tasks but also with greater variability in performance. Through
novel meta-analytic techniques, we demonstrate a negative effect size for mean
differences (-.457), but a positive effect size for SD differences (+.118; SD
ratio = 1.107). In doing so, this is the first study to demonstrate impoverished
visuospatial processing of the majority of individuals with dyslexia in addition
to greater variance in performance in this group. The findings advocate for
further consideration of both the presence of, and reasons for, increased
variance in perception, attention, and memory across neurodevelopmental
disorders.
PMID- 29938777
TI - Genetic characterization and therapeutic targeting of MYC-rearranged T cell acute
lymphoblastic leukaemia.
PMID- 29938779
TI - Advances in understanding iron metabolism and its crosstalk with erythropoiesis.
AB - Recent years have witnessed impressive advances in our understanding of iron
metabolism. A number of studies of iron disorders and of their animal models have
provided landmark insights into the mechanisms of iron trafficking, distribution
and homeostatic regulation, the latter essential to prevent both iron deficiency
and iron excess. Our perception of iron metabolism has been completely changed by
an improved definition of cellular and systemic iron homeostasis, of the
molecular pathogenesis of iron disorders, the fine tuning of the iron hormone
hepcidin by activators and inhibitors and the dissection of the components of the
hepcidin regulatory pathway. Important for haematology, the crosstalk of
erythropoiesis, the most important iron consumer, and the hepcidin pathway has
been at least partially clarified. Novel potential biomarkers are available and
novel therapeutic targets for iron-related disorders have been tested in murine
models. These preclinical studies provided proofs of principle and are laying the
ground for clinical trials. Understanding iron control in tissues other than
erythropoiesis remains a challenge for the future.
PMID- 29938778
TI - Oxidative stress and phosphatidylserine exposure in red cells from patients with
sickle cell anaemia.
AB - Phosphatidylserine (PS) exposure increases as red cells age, and is an important
signal for the removal of senescent cells from the circulation. PS exposure is
elevated in red cells from sickle cell anaemia (SCA) patients and is thought to
enhance haemolysis and vaso-occlusion. Although precise conditions leading to its
externalisation are unclear, high intracellular Ca2+ has been implicated. Red
cells from SCA patients are also exposed to an increased oxidative challenge, and
we postulated that this stimulates PS exposure, through increased Ca2+ levels. We
tested four different ways of generating oxidative stress: hypoxanthine and
xanthine oxidase, phenazine methosulphate, nitrite and tert-butyl hydroperoxide,
together with thiol modification with N-ethylmaleimide (NEM), dithiothreitol and
hypochlorous acid (HOCl), in red cells permeabilised to Ca2+ using bromo-A23187.
Unexpectedly, our findings showed that the four oxidants significantly reduced
Ca2+ -induced PS exposure (by 40-60%) with no appreciable effect on Ca2+
affinity. By contrast, NEM markedly increased PS exposure (by about 400%) and
slightly but significantly increased the affinity for Ca2+ . Dithiothreitol
modestly reduced PS exposure (by 25%) and HOCl had no effect. These findings
emphasise the importance of thiol modification for PS exposure in sickle cells
but suggest that increased oxidant stress alone is not important.
PMID- 29938780
TI - The presence of mutated and deleted PTEN is associated with an increased risk of
relapse in childhood T cell acute lymphoblastic leukaemia treated with AIEOP-BFM
ALL protocols.
AB - Notwithstanding the improvement in treatment results for paediatric T cell acute
lymphoblastic leukaemia (T-ALL) it remains important to understand if genetic
aberrations influence therapy response. PTEN tumour suppressor gene inactivation
is a frequent event in T-ALL but its effect on patient therapy response is
debatable. We analysed the effect of the presence of mutated PTEN on outcome in
257 children with T-ALL treated with Associazione Italiana di Ematologia e
Oncologia Pediatrica (AIEOP)-Berlin-Frankfurt-Munster (BFM) protocols. PTEN
mutations were present in 31 (12.1%) patients and were significantly associated
with increased risk of relapse. PTEN mutations also indicate a poor prognosis in
T-ALL patients in the absence of NOTCH1 mutations or in the group of patients
with co-presence of PTEN mutation and deletions. These results indicate that PTEN
genomic aberrations and the biologically consequential PTEN inactivation
contribute to adverse therapy response in T-ALL patients; PTEN status as a
biomarker may contribute to the development of new molecularly-defined
stratification algorithms.
PMID- 29938781
TI - Insights into the musculature of the bonobo hand.
AB - The human hand is well known for its unique dexterity which is largely
facilitated by a highly mobile, long and powerful thumb that enables both tool
manufacturing and use, a key component of human evolution. The bonobo (Pan
paniscus), the closest extant relative to modern humans together with the
chimpanzee (Pan troglodytes), also possesses good manipulative capabilities but
with a lower level of dexterity compared with modern humans. Despite the close
phylogenetic relationship between bonobos and humans, detailed quantitative data
of the bonobo forelimb musculature remains largely lacking. To understand how
morphology may influence dexterity, we investigated the functional anatomy of the
bonobo hand using a unique sample of eight bonobo cadavers, along with one
chimpanzee and one human (Homo sapiens) cadaver. We performed detailed
dissections of unembalmed specimens to collect quantitative datasets of the
extrinsic and intrinsic hand musculature, in addition to qualitative descriptions
of the forelimb muscle configurations, allowing estimation of force-generating
capacities for each functional group. Furthermore, we used medical imaging to
quantify the articular surface of the trapeziometacarpal joint to estimate the
intra-articular pressure. Our results show that the force-generating capacity for
most functional groups of the extrinsic and intrinsic hand muscles in bonobos is
largely similar to that of humans, with differences in relative importance of the
extensors and rotators. The bonobo thumb musculature has a lower force-generating
capacity than observed in the human specimen, but the estimated maximal intra
articular pressure is higher in bonobos. Most importantly, bonobos show a higher
degree of functional coupling between the muscles of the thumb, index and lateral
fingers than observed in humans. It is conceivable that differentiation and
individualization of the hand muscles rather than relative muscle development
explain the higher level of dexterity of humans compared with that of bonobos.
PMID- 29938782
TI - Mexican-Origin Youth's Cultural Orientations and Values: Do Older Sisters and
Brothers Matter?
AB - Family is an important context for cultural development, but little is known
about the contributions of siblings. This study investigated whether older
siblings' cultural orientations and familism values predicted changes in younger
siblings' cultural orientations and familism values across 2 years and tested
sibling characteristics and younger siblings' modeling as moderators.
Participants were 246 Mexican-origin younger (Mage = 17.72; SD = 0.57) and older
siblings (Mage = 20.65; SD = 1.57) and their parents. Findings revealed that
older siblings' Anglo orientations and familism values interacted with younger
siblings' modeling: When younger siblings reported high modeling, older siblings'
Anglo orientations and values predicted increases in younger siblings' Anglo
orientations and values. Discussion highlights the importance of siblings in
cultural socialization.
PMID- 29938784
TI - Brain derived neurotropic factor single nucleotide polymorphism Val66Met and
serum protein levels are associated with development of vincristine-induced
peripheral neuropathy in patients with lymphoma.
PMID- 29938783
TI - Scleroderma-like cutaneous lesions during treatment with paclitaxel and
gemcitabine in a patient with pancreatic adenocarcinoma. Review of literature.
AB - BACKGROUND: Chemotherapy-induced skin sclerosis is generally not associated with
other manifestations of systemic sclerosis. It is featured by skin sclerosis
without visceral involvement (i.e., Raynaud's phenomenon, esophageal dysmotility,
and pulmonary fibrosis), temporal association with chemotherapy administration,
and the absence of detectable autoantibodies. The clinical course of scleroderma
like changes induced by paclitaxel or gemcitabine are refractory to treatment and
commonly progressive, even after discontinuation of the triggering drugs.
OBJECTIVE: Report a case of scleroderma-like cutaneous lesions during combination
treatment with nab-paclitaxel and gemcitabine in a patient with pancreatic
adenocarcinoma and determine other published cases of scleroderma-like skin
changes following treatment with nab-paclitaxel, paclitaxel, or gemcitabine
through the period from 2002 to 2018. METHODS: Literature search from the year
2002 onwards using combinations of "Scleroderma" AND "paclitaxel," AND/OR
"gemcitabine." RESULTS: Additional to our case report we reviewed 14 other cases
in the literature. Most of these cases share three prominent features: skin
sclerosis without systemic involvement, temporal association with chemotherapy
administration, and absence of detectable scleroderma-specific autoantibodies.
CONCLUSION: To our knowledge, this is the first case report of scleroderma-like
cutaneous lesions during combination treatment with nab-paclitaxel and
gemcitabine in a patient with pancreatic adenocarcinoma. However, given the
current literature, these scleroderma-like lesions are most likely induced by nab
paclitaxel or paclitaxel, rather than by gemcitabine.
PMID- 29938785
TI - Family socioeconomic status and emotional adaptation among rural-to-urban migrant
adolescents in China: The moderating roles of adolescent's resilience and
parental positive emotion.
AB - Low family socioeconomic status (SES) is closely related to increased risk of
emotional maladaptation among adolescents. Although previous studies have found
that low family SES is a significant and common experience for most rural-to
urban migrant adolescents in China, little research has examined the association
between family SES and emotional adaptation or identified the protective factors
that may minimise emotional maladaptation among these adolescents. The present
study examined the associations between family SES and three indices of emotional
adaptation (emotion regulation, life satisfaction and depression) and the
moderating effects of adolescents' resilience and parental positive emotion (PE)
among 486 Chinese rural-to-urban migrant adolescents. The results suggest that
family SES was significantly associated with migrant adolescents' emotional
outcomes, to varying degrees. Moreover, both adolescents' resilience and PE
moderated the associations between family SES and emotional outcomes, although
the protective effects of the two moderators differed on the three emotional
outcomes. These findings shed light into designing intervention and prevention
programs to reduce emotional maladaptation among migrant adolescents.
PMID- 29938786
TI - Victimization Disparities Between Heterosexual and Sexual Minority Youth From
Ages 9 to 15.
AB - Mental health disparities between heterosexual and sexual minority youth are
partly explained by the higher rates of victimization experienced by sexual
minority youth. The onset and progression of these victimization disparities,
however, are poorly understood. Using multirater longitudinal data, trajectories
of victimization starting at age 9 were compared among youth who did and did not
report same-sex attraction at age 15 (N = 310). Self and teacher, but not primary
caregivers, reported victimization was significantly higher among sexual minority
youth starting at age 9, but did not vary across time. The findings underscore
the importance of understanding homophobic experiences of sexual minority youth
during late childhood and early adolescence in order to inform prevention
programs.
PMID- 29938787
TI - Inbreeding intensifies sex- and age-dependent disease in a wild mammal.
AB - The mutation accumulation theory of senescence predicts that age-related
deterioration of fitness can be exaggerated when inbreeding causes homozygosity
for deleterious alleles. A vital component of fitness, in natural populations, is
the incidence and progression of disease. Evidence is growing for natural links
between inbreeding and ageing; between inbreeding and disease; between sex and
ageing; and between sex and disease. However, there is scant evidence, to date,
for links among age, disease, inbreeding and sex in a single natural population.
Using ecological and epidemiological data from a long-term longitudinal field
study, we show that in wild European badgers (Meles meles) exposed naturally to
bovine tuberculosis (bTB), inbreeding (measured as multilocus homozygosity)
intensifies a positive correlation between age and evidence of progressed
infection (measured as an antibody response to bTB), but only among females. Male
badgers suffer a steeper relationship between age and progressed infection than
females, with no influence of inbred status. We found no link between inbreeding
and the incidence of progressed infection during early life in either sex. Our
findings highlight an age-related increase in the impact of inbreeding on a
fitness-relevant trait (disease state) among females. This relationship is
consistent with the predictions of the mutation accumulation theory of
senescence, but other mechanisms could also play a role. For example, late-life
declines in condition, arising through mechanisms other than mutation
accumulation might have increased the magnitude of inbreeding depression in late
life. Whichever mechanism causes the observed patterns, we have shown that
inbreeding can influence age-dependent patterns of disease and, by extension, is
likely to affect the magnitude and timing of the late-life declines in components
of fitness that characterise senescence. Better understanding of sex-specific
links between inbreeding, disease and ageing provides insights into population
level pathogen dynamics and could influence management strategies for wildlife
reservoirs of zoonotic disease.
PMID- 29938788
TI - Index of host habitat preference explored by movement-based simulations and trap
captures.
AB - Animal species likely have different strengths of host habitat preference (HHP)
that might be characterized by a standardized index ranging from 0 (no
preference) to 1 (maximum preference). We hypothesized that in some species, HHP
may result from individuals dispersing out of the host habitat having a
probability of turning back at the boundary, or after entering host habitat by
reducing speed or increasing size of turning angles. Computer simulations of
individuals moving between various sized patches of host and nonhost habitat were
conducted based on these three behaviours hypothesized to affect HHP. In the
rebounding model, simulations resulted in equilibria of animal numbers inside and
outside of host habitat that depend on sizes of these areas, initial number and
the rebounding probability. Curvilinear regression of simulation results
suggested an equation that predicted numbers in the host habitat and was solved
for rebounding probability. A modified equation that sampled population densities
(e.g., insect pheromone trap catches) inside and outside host habitat areas gave
the rebounding probability, an index of HHP, without requiring the sizes of the
areas. Simulations with traps and moving animals verified that the modified
equation could predict the index correctly. The modified equation also estimates
an index of HHP from sampled densities due to speed reductions and a combination
of this and rebounding. Changes in angular turning size upon entering host
habitat, however, did not affect habitat preference. Using pheromone trap
captures, we found that the lesser date moth Batrachedra amydraula has a HHP for
date Phoenix dactylifera plantations of 0.96. Host habitat preference indexes
also were calculated from sampled insect densities reported in the literature.
The new index of HHP is useful to characterize habitat patches of many organisms
and aid understanding of animal spatial distributions and speciation processes.
In addition, the index can be applied in studies of invasive species, trap crops
of pest insects and conservation management.
PMID- 29938789
TI - Antibiotics for exacerbations of asthma.
AB - BACKGROUND: Asthma is a chronic respiratory condition that affects over 300
million adults and children worldwide. It is characterised by wheeze, cough,
chest tightness, and shortness of breath. Symptoms typically are intermittent and
may worsen over a short time, leading to an exacerbation. Asthma exacerbations
can be serious, leading to hospitalisation or even death in rare cases.
Exacerbations may be treated by increasing an individual's usual medication and
providing additional medication, such as oral steroids. Although antibiotics are
sometimes included in the treatment regimen, bacterial infections are thought to
be responsible for only a minority of exacerbations, and current guidance states
that antibiotics should be reserved for cases in which clear signs, symptoms, or
laboratory test results are suggestive of bacterial infection. OBJECTIVES: To
determine the efficacy and safety of antibiotics in the treatment of asthma
exacerbations. SEARCH METHODS: We searched the Cochrane Airways Trials Register,
which contains records compiled from multiple electronic and handsearched
resources. We also searched trial registries and reference lists of primary
studies. We conducted the most recent search in October 2017. SELECTION CRITERIA:
We included studies comparing antibiotic therapy for asthma exacerbations in
adults or children versus placebo or usual care not involving an antibiotic. We
allowed studies including any type of antibiotic, any dose, and any duration,
providing the aim was to treat the exacerbation. We included parallel studies of
any duration conducted in any setting and planned to include cluster trials. We
excluded cross-over trials. We included studies reported as full-text articles,
those published as abstracts only, and unpublished data. DATA COLLECTION AND
ANALYSIS: At least two review authors screened the search results for eligible
studies. We extracted outcome data, assessed risk of bias in duplicate, and
resolved discrepancies by involving another review author. We analysed
dichotomous data as odds ratios (ORs) or risk differences (RDs), and continuous
data as mean differences (MDs), all with a fixed-effect model. We described
skewed data narratively. We graded the results and presented evidence in 'Summary
of findings' tables for each comparison. Primary outcomes were intensive care
unit/high dependence unit (ICU/HDU) admission, duration of
symptoms/exacerbations, and all adverse events. Seconday outcomes were mortality,
length of hospital admission, relapse after index presentation, and peak
expiratory flow rate (PEFR). MAIN RESULTS: Six studies met our inclusion criteria
and included a total of 681 adults and children with exacerbations of asthma.
Mean age in the three studies in adults ranged from 36.2 to 41.2 years. The three
studies in children applied varied inclusion criteria, ranging from one to 18
years of age. Five studies explicitly excluded participants with obvious signs
and symptoms of bacterial infection (i.e. those clearly meeting current guidance
to receive antibiotics). Four studies investigated macrolide antibiotics, and two
studies investigated penicillin (amoxicillin and ampicillin) antibiotics; both
studies using penicillin were conducted over 35 years ago. Five studies compared
antibiotics versus placebo, and one was open-label. Study follow-up ranged from
one to twelve weeks. Trials were of varied methodological quality, and we were
able to perform only limited meta-analysis.None of the included trials reported
ICU/HDU admission, although one participant in the placebo group of a study
including children with status asthmaticus experienced a respiratory arrest and
was ventilated. Four studies reported asthma symptoms, but we were able to
combine results for only two macrolide studies of 416 participants; the MD in
diary card symptom score was -0.34 (95% confidence interval (CI) -0.60 to -0.08),
with lower scores (on a 7 point scale) denoting improved symptoms. Two macrolide
studies reported symptom-free days. One study of 255 adults authors reported the
percentage of symptom-free days at 10 days as 16% in the antibiotic group and 8%
in the placebo group. In a further study of 40 children study authors reported
significantly more symptom-free days at all time points in the antibiotic group
compared with the usual care group. The same study reported the duration in days
of the index asthma exacerbation, again favouring the antibiotic group. One study
of a penicillin including 69 participants reported asthma symptoms at hospital
discharge; the between-group difference for both studies was reported as non
significant.We combined data for serious adverse events from three studies
involving 502 participants, but events were rare; the three trials reported only
10 events: five in the antibiotic group and five in the placebo group. We
combined data for all adverse events (AEs) from three studies, but the effect
estimate is imprecise (OR 0.99, 95% CI 0.69 to 1.43). No deaths were reported in
any of the included studies.Two studies investigating penicillins reported
admission duration; neither study reported a between-group difference. In one
study (263 participants) of macrolides, two participants in each arm were
reported as experiencing a relapse, defined as a further exacerbation, by the six
week time points. We combined PEFR endpoint results at 10 days for two macrolide
studies; the result favoured antibiotics over placebo (MD 23.42 L/min, 95% CI
5.23 to 41.60). One study in children reported the maximum peak flow recorded
during the follow-up period, favouring the clarithromycin group, but the
confidence interval includes no difference (MD 38.80, 95% CI -11.19 to
88.79).Grading of outcomes ranged from moderate to very low quality, with quality
of outcomes downgraded for suspicion of publication bias, indirectness,
imprecision, and poor methodological quality of studies. AUTHORS' CONCLUSIONS: We
found limited evidence that antibiotics given at the time of an asthma
exacerbation may improve symptoms and PEFR at follow-up compared with standard
care or placebo. However, findings were inconsistent across the six heterogeneous
studies included, two of the studies were conducted over 30 years ago and most of
the participants included in this review were recruited from emergency
departments, limiting the applicability of findings to this population. Therefore
we have limited confidence in the results. We found insufficient evidence about
several patient-important outcomes (e.g. hospital admission) to form conclusions.
We were unable to rule out a difference between groups in terms of all adverse
events, but serious adverse events were rare.
PMID- 29938790
TI - Automated monitoring compared to standard care for the early detection of sepsis
in critically ill patients.
AB - BACKGROUND: Sepsis is a life-threatening condition that is usually diagnosed when
a patient has a suspected or documented infection, and meets two or more criteria
for systemic inflammatory response syndrome (SIRS). The incidence of sepsis is
higher among people admitted to critical care settings such as the intensive care
unit (ICU) than among people in other settings. If left untreated sepsis can
quickly worsen; severe sepsis has a mortality rate of 40% or higher, depending on
definition. Recognition of sepsis can be challenging as it usually requires
patient data to be combined from multiple unconnected sources, and interpreted
correctly, which can be complex and time consuming to do. Electronic systems that
are designed to connect information sources together, and automatically collate,
analyse, and continuously monitor the information, as well as alerting healthcare
staff when pre-determined diagnostic thresholds are met, may offer benefits by
facilitating earlier recognition of sepsis and faster initiation of treatment,
such as antimicrobial therapy, fluid resuscitation, inotropes, and vasopressors
if appropriate. However, there is the possibility that electronic, automated
systems do not offer benefits, or even cause harm. This might happen if the
systems are unable to correctly detect sepsis (meaning that treatment is not
started when it should be, or it is started when it shouldn't be), or healthcare
staff may not respond to alerts quickly enough, or get 'alarm fatigue' especially
if the alarms go off frequently or give too many false alarms. OBJECTIVES: To
evaluate whether automated systems for the early detection of sepsis can reduce
the time to appropriate treatment (such as initiation of antibiotics, fluids,
inotropes, and vasopressors) and improve clinical outcomes in critically ill
patients in the ICU. SEARCH METHODS: We searched CENTRAL; MEDLINE; Embase;
CINAHL; ISI Web of science; and LILACS, clinicaltrials.gov, and the World Health
Organization trials portal. We searched all databases from their date of
inception to 18 September 2017, with no restriction on country or language of
publication. SELECTION CRITERIA: We included randomized controlled trials (RCTs)
that compared automated sepsis-monitoring systems to standard care (such as paper
based systems) in participants of any age admitted to intensive or critical care
units for critical illness. We defined an automated system as any process capable
of screening patient records or data (one or more systems) automatically at
intervals for markers or characteristics that are indicative of sepsis. We
defined critical illness as including, but not limited to postsurgery, trauma,
stroke, myocardial infarction, arrhythmia, burns, and hypovolaemic or
haemorrhagic shock. We excluded non-randomized studies, quasi-randomized studies,
and cross-over studies . We also excluded studies including people already
diagnosed with sepsis. DATA COLLECTION AND ANALYSIS: We used the standard
methodological procedures expected by Cochrane. Our primary outcomes were: time
to initiation of antimicrobial therapy; time to initiation of fluid
resuscitation; and 30-day mortality. Secondary outcomes included: length of stay
in ICU; failed detection of sepsis; and quality of life. We used GRADE to assess
the quality of evidence for each outcome. MAIN RESULTS: We included three RCTs in
this review. It was unclear if the RCTs were three separate studies involving
1199 participants in total, or if they were reports from the same study involving
fewer participants. We decided to treat the studies separately, as we were unable
to make contact with the study authors to clarify.All three RCTs are of very low
study quality because of issues with unclear randomization methods, allocation
concealment and uncertainty of effect size. Some of the studies were reported as
abstracts only and contained limited data, which prevented meaningful analysis
and assessment of potential biases.The studies included participants who all
received automated electronic monitoring during their hospital stay. Participants
were randomized to an intervention group (automated alerts sent from the system)
or to usual care (no automated alerts sent from the system).Evidence from all
three studies reported 'Time to initiation of antimicrobial therapy'. We were
unable to pool the data, but the largest study involving 680 participants
reported median time to initiation of antimicrobial therapy in the intervention
group of 5.6 hours (interquartile range (IQR) 2.3 to 19.7) in the intervention
group (n = not stated) and 7.8 hours (IQR 2.5 to 33.1) in the control group (n =
not stated).No studies reported 'Time to initiation of fluid resuscitation' or
the adverse event 'Mortality at 30 days'. However very low-quality evidence was
available where mortality was reported at other time points. One study involving
77 participants reported 14-day mortality of 20% in the intervention group and
21% in the control group (numerator and denominator not stated). One study
involving 442 participants reported mortality at 28 days, or discharge was 14% in
the intervention group and 10% in the control group (numerator and denominator
not reported). Sample sizes were not reported adequately for these outcomes and
so we could not estimate confidence intervals.Very low-quality evidence from one
study involving 442 participants reported 'Length of stay in ICU'. Median length
of stay was 3.0 days in the intervention group (IQR = 2.0 to 5.0), and 3.0 days
(IQR 2.0 to 4.0 in the control).Very low-quality evidence from one study
involving at least 442 participants reported the adverse effect 'Failed detection
of sepsis'. Data were only reported for failed detection of sepsis in two
participants and it wasn't clear which group(s) this outcome occurred in.No
studies reported 'Quality of life'. AUTHORS' CONCLUSIONS: It is unclear what
effect automated systems for monitoring sepsis have on any of the outcomes
included in this review. Very low-quality evidence is only available on automated
alerts, which is only one component of automated monitoring systems. It is
uncertain whether such systems can replace regular, careful review of the
patient's condition by experienced healthcare staff.
PMID- 29938791
TI - Drivers of individual niche variation in coexisting species.
AB - Although neglected by classic niche theory, individual variation is now
recognized as a prevalent phenomenon in nature with evolutionary and ecological
relevance. Recent theory suggests that differences in individual variation across
competitors can affect species coexistence and community patterns. However, the
degree of individual variation is flexible across wild populations and we still
know little about the ecological drivers of this variation across populations of
single species and, especially, across coexisting species. Here, we aimed to (a)
elucidate the major drivers of individual niche variation in natural communities
and (b) to determine how consistent this variation is across coexisting species
and communities. We analysed natural patterns of individual-level niche variation
in four species of coexisting generalist frogs across a wide range of tropical
communities. Specifically, we used gut contents and stable isotopes (delta13 C
and delta15 N) from frog species and their prey to quantify individual niche
specialization. Then, we combined data on local community structure, availability
of prey, phylogenetic relationships and predator-prey size models to test how
this variation is related to four ecological factors which are predicted to be
key drivers of individual specialization: intraspecific competition,
interspecific competition, ecological opportunity (i.e., diversity of resources)
and predation. We found that the degree of individual trophic specialization
varied by up to ninefold across populations within the same species. This sizable
variation in trophic specialization across populations was at least partially
explained by gradients of density of competitors (both conspecifics and
heterospecifics) and intraguild predation. However, the specific relationships
between individual specialization and these ecological gradients were strongly
species-specific. As consequences, the identity of the species with more
individual variation changed among sites and there was typically no spatial
correlation in the degree of individual specialization across coexisting species.
Our results show that individual niche specialization within and across species
can be strongly context-dependent and that hierarchies of individual variation
among coexisting species are not necessarily consistent across communities.
Recent theory suggests that this pattern could lead to concurrent changes in
competitive interactions across sites and thereby could play a key role in
species coexistence at the landscape level. Our results suggest that individual
variation across and within coexisting species has the potential to affect not
only species coexistence at local communities, but also regional diversity
patterns.
PMID- 29938792
TI - Evidence for HNRNPH1 being another gene for Bain type syndromic mental
retardation.
AB - The HNRNPH2-associated disease (mental retardation, X-linked, syndromic, Bain
type [MRXSB, MIM #300986]) is caused by de novo mutations in the X-linked HNRNPH2
gene. MRXSB has been described in six female patients with dysmorphy,
developmental delay, intellectual disability, autism, hypotonia and seizures. The
reported HNRNPH2 mutations were clustered in the small domain encoding nuclear
localization signal; in particular, the p.Arg206Trp was found in four independent
de novo events. HNRNPH1 is a conserved autosomal paralogue of HNRNPH2 with a
similar function in regulation of pre-mRNAs splicing but so far it has not been
associated with human disease. We describe a boy with a disease similar to MRXSB
in whom a novel de novo mutation c.616C>T (p.Arg206Trp) in HNRNPH1 was found (ie,
the exact paralogue of the recurrent HNRNPH2 mutation). We propose that defective
function of HNRNPH2 and HNRNPH1 nuclear localization signal has similar clinical
consequences. An important difference between the two diseases is that the
HNRNPH1-associated syndrome may occur in boys (as in the case of our proband)
which is well explained by the autosomal (chr5q35.3) rather than X-linked
localization of the HNRNPH2 gene.
PMID- 29938793
TI - In vivo virulence and genomic comparison of infectious Salmon Anaemia Virus
isolates from Atlantic Canada.
AB - The infectious salmon anaemia virus (ISAV) is capable of causing a significant
disease in Atlantic salmon, which has resulted in considerable financial losses
for salmon farmers around the world. Since the first detection of ISAV in Canada
in 1996, it has been a high priority for aquatic animal health management and
surveillance programmes have led to the identification of many genetically
distinct ISAV isolates of variable virulence. In this study, we evaluated the
virulence of three ISAV isolates detected in Atlantic Canada in 2012 by doing in
vivo-controlled disease challenges with two sources of Atlantic salmon. We
measured viral loads in fish tissues during the course of infection. Sequences of
the full viral RNA genomes of these three ISAV isolates were obtained and
compared to a high-virulence and previously characterized isolate detected in the
Bay of Fundy in 2004, as well as a newly identified ISAV NA-HPR0 isolate. All
three ISAV isolates studied were shown to be of low to mid-virulence with fish
from source A having a lower mortality rate than fish from source B. Viral load
estimation using an RT-qPCR assay targeting viral segment 8 showed a high degree
of similarity between tissues. Through genomic comparison, we identified various
amino acid substitutions unique to some isolates, including a stop codon in the
segment 8 ORF2 not previously reported in ISAV, present in the isolate with the
lowest observed virulence.
PMID- 29938794
TI - Age-related changes in cardiac electrophysiology and calcium handling in response
to sympathetic nerve stimulation.
AB - KEY POINTS: Ageing results in changes to cardiac electrophysiology, Ca2+
handling, and beta-adrenergic responsiveness. Sympathetic neurodegeneration also
occurs with age, yet detailed action potential and Ca2+ handling responses to
physiological sympathetic nerve stimulation (SNS) in the aged heart have not been
assessed. Optical mapping in mouse hearts with intact sympathetic innervation
revealed reduced responsiveness to SNS in the aged atria (assessed by heart rate)
and aged ventricles (assessed by action potentials and Ca2+ transients).
Sympathetic nerve density and noradrenaline content were reduced in aged
ventricles, but noradrenaline content was preserved in aged atria. These results
demonstrate that reduced responsiveness to SNS in the atria may be primarily due
to decreased beta-adrenergic receptor responsiveness, whereas reduced
responsiveness to SNS in the ventricles may be primarily due to
neurodegeneration. ABSTRACT: The objective of this study was to determine how age
related changes in sympathetic structure and function impact cardiac
electrophysiology and intracellular Ca2+ handling. Innervated hearts from young
(3-4 months, YWT, n = 10) and aged (20-24 months, AGED, n = 11) female mice
(C57Bl6) were optically mapped using the voltage (Vm ,)- and calcium (Ca2+ )
sensitive indicators Rh237 and Rhod2-AM. Sympathetic nerve stimulation (SNS) was
performed at the spinal cord (T1-T3). beta-Adrenergic responsiveness was assessed
with isoproterenol (1 MUM, ISO). Sympathetic nerve density and noradrenaline
content were also quantified. Stimulation thresholds necessary to produce a
defined increase in heart rate (HR) with SNS were higher in AGED vs. YWT hearts
(5.4 +/- 0.4 vs. 3.8 +/- 0.4 Hz, P < 0.05). Maximal HR with SNS was lower in AGED
vs. YWT (20.5 +/- 3.41% vs. 73.0 +/- 7.63% increase, P < 0.05). beta-Adrenergic
responsiveness of the atria (measured as percentage increase in HR with ISO) was
decreased in AGED vs. YWT hearts (75.3 +/- 22.5% vs. 148.5 +/- 19.8%, P < 0.05).
SNS significantly increased action potential duration (APD) in YWT but not AGED.
Ca2+ transient durations and rise times were unchanged by SNS, yet AGED hearts
had an increased susceptibility to Ca2+ alternans and ventricular arrhythmias.
beta-Adrenergic responsiveness of all ventricular parameters were similar between
AGED and YWT. Sympathetic nerve density and noradrenaline content were decreased
in the AGED ventricle, but not atria, compared to YWT. These data suggest that
decreased responsiveness to SNS in the aged atria may be primarily due to
decreased beta-adrenergic responsiveness, whereas decreased responsiveness to SNS
in the aged ventricles may be primarily due to nerve degeneration.
PMID- 29938795
TI - Effects of dietary supplementation with oregano essential oil on prevention of
the ectoparasitic protozoans Ichthyobodo salmonis and Trichodina truttae in
juvenile chum salmon Oncorhynchus keta.
AB - The present study performed three experiments to establish a practical prevention
strategy for the ectoparasitic flagellate Ichthyobodo salmonis and ciliate
Trichodina truttae in hatchery-reared juvenile chum salmon Oncorhynchus keta
using dietary supplementation with oregano essential oil. Experiment 1 showed
that a diet supplemented for 3 weeks with 0.02% oregano essential oil
significantly prevented infection with I. salmonis and T. truttae in juveniles
reared in small tanks. Experiment 2, in outdoor hatchery ponds, demonstrated that
the oregano treatment completely prevented I. salmonis infection for 52 days and
T. truttae infection for 38 days. Oregano-treated juvenile mortality attributable
to infection with these protozoans also decreased to 7.6% of control juvenile
mortality, confirming the utility of this treatment in cultured O. keta.
Physiological analyses of the oregano-treated juveniles elucidated the
treatment's safety in relation to their metabolism, osmoregulation, natural
immunity and olfactory responses and also detected carvacrol (a major component
of oregano essential oil which shows antimicrobial activity) on the skin. In
experiment 3, exposure of the two protozoans to oregano essential oil revealed a
weak antiparasitic action on the body surface of the juvenile O. keta. The
overall results demonstrate that dietary oregano supplementation is a practical
prevention strategy for I. salmonis and T. truttae in hatchery-reared juvenile O.
keta and suggest the possibility that its anti-parasitic action is attributable
to a component of the oil that emerges onto the skin of the body of the fish.
PMID- 29938796
TI - Climate change leads to accelerated transformation of high-elevation vegetation
in the central Alps.
AB - High mountain ecosystems and their biota are governed by low-temperature
conditions and thus can be used as indicators for climate warming impacts on
natural ecosystems, provided that long-term data exist. We used data from the
largest alpine to nival permanent plot site in the Alps, established in the frame
of the Global Observation Research Initiative in Alpine Environments (GLORIA) on
Schrankogel in the Tyrolean Alps, Austria, in 1994, and resurveyed in 2004 and
2014. Vascular plant species richness per plot increased over the entire period,
albeit to a lesser extent in the second decade, because disappearance events
increased markedly in the latter period. Although presence/absence data could
only marginally explain range shift dynamics, changes in species cover and plant
community composition indicate an accelerating transformation towards a more
warmth-demanding and more drought-adapted vegetation, which is strongest at the
lowest, least rugged subsite. Divergent responses of vertical distribution groups
of species suggest that direct warming effects, rather than competitive
displacement, are the primary causes of the observed patterns. The continued
decrease in cryophilic species could imply that trailing edge dynamics proceed
more rapidly than successful colonisation, which would favour a period of
accelerated species declines.
PMID- 29938797
TI - Two methods for reducing moving metal artifacts in cone-beam CT.
AB - PURPOSE: In image-guided radiation therapy, fiducial markers or clips are often
used to determine the position of the tumor. These markers lead to streak
artifacts in cone-beam CT (CBCT) scans. Standard inpainting-based metal artifact
reduction (MAR) methods fail to remove these artifacts in cases of large motion.
We propose two methods to effectively reduce artifacts caused by moving metal
inserts. METHODS: The first method (MMAR) utilizes a coarse metal segmentation in
the image domain and a refined segmentation in the rawdata domain. After an
initial reconstruction, metal is segmented and forward projected giving a coarse
metal mask in the rawdata domain. Inside the coarse mask, metal is segmented by
utilizing a 2D Sobel filter. Metal is removed by linear interpolation in the
refined metal mask. The second method (MoCoMAR) utilizes a motion compensation
(MoCo) algorithm [Med Phys. 2013;40:101913] that provides us with a motion-free
volume (3D) or with a time series of motion-free volumes (4D). We then apply the
normalized metal artifact reduction (NMAR) [Med Phys. 2010;37:5482-5493] to these
MoCo volumes. Both methods were applied to three CBCT data sets of patients with
metal inserts in the thorax or abdomen region and a 4D thorax simulation. The
results were compared to volumes corrected by a standard MAR1 [Radiology.
1987;164:576-577]. RESULTS: MMAR and MoCoMAR were able to remove all artifacts
caused by moving metal inserts for the patients and the simulation. Both new
methods outperformed the standard MAR1, which was only able to remove artifacts
caused by metal inserts with little or no motion. CONCLUSIONS: In this work, two
new methods to remove artifacts caused by moving metal inserts are introduced.
Both methods showed good results for a simulation and three patients. While the
first method (MMAR) works without any prior knowledge, the second method
(MoCoMAR) requires a respiratory signal for the MoCo step and is computationally
more demanding and gives no benefit over MMAR, unless MoCo images are desired.
PMID- 29938798
TI - Protein hydrolysates and ultrafiltered < 1 KDa fractions from Phaseolus lunatus,
Phaseolus vulgaris and Mucuna pruriens exhibit antihyperglycemic activity,
intestinal glucose absorption and alpha-glucosidase inhibition with no acute
toxicity in rodents.
AB - BACKGROUND: Protein hydrolysates from food plants, such as legumes, have emerged
as a new alternative to treat hyperglycemia, an important risk factor
contributing to the development of type 2 diabetes mellitus (T2DM) and its
complications. The aim of this work was to assess the antihyperglycemic activity
and inhibition of alpha-glucosidase, and intestinal glucose absorption, and acute
toxicity of total hydrolysates and < 1 kDa fractions from Phaseolus lunatus L.,
Phaseolus vulgaris L., and Mucuna pruriens (L.) DC., obtained by hydrolysis with
Alcalase(r)-Flavourzyme(r) or pepsine-pancreatin enzymatic systems. RESULTS: In
vivo results showed that three of six total hydrolysates and four of six < 1 kDa
fractions suppressed starch-induced postprandial hyperglycemia (ED50 range
between 1.4 and 93 mg kg-1 ). In vitro, total hydrolysates and fractions,
particularly from M. pruriens, inhibited carbohydrate intestinal absorption (from
19.2 to 40%), and alpha-glucosidase activity (IC50 from 0.86 to 75 mg mL-1 ).
Finally, none of the hydrolysates and fractions tested did not show any signs of
toxicity (LD50 > 5000 mg kg-1 ). CONCLUSION: These results suggest that
hydrolysates and < 1 kDa fractions from P. lunatus, P. vulgaris and M. pruriens
are suitable candidates to treat or prevent T2DM. (c) 2018 Society of Chemical
Industry.
PMID- 29938799
TI - Repeated sublethal freshwater exposures reduce the amoebic gill disease parasite,
Neoparamoeba perurans, on Atlantic salmon.
AB - Freshwater bathing is one of the main treatment options available against amoebic
gill disease (AGD) affecting multiple fish hosts in mariculture systems.
Prevailing freshwater treatments are designed to be long enough to kill
Neoparamoeba perurans, the ectoparasite causing AGD, which may select for
freshwater tolerance. Here, we tested whether using shorter, sublethal freshwater
treatment durations are a viable alternative to lethal ones for N. perurans (2-4
hr). Under in vitro conditions, gill-isolated N. perurans attached to plastic
substrate in sea water lifted off after >=2 min in freshwater, but survival was
not impacted until 60 min. In an in vivo experiment, AGD-affected Atlantic salmon
Salmo salar subjected daily to 30 min (sublethal to N. perurans) and 120 min
(lethal to N. perurans) freshwater treatments for 6 days consistently reduced N.
perurans cell numbers on gills (based on qPCR analysis) compared to daily 3 min
freshwater or seawater treatments for 6 days. Our results suggest that targeting
cell detachment rather than cell death with repeated freshwater treatments of
shorter duration than typical baths could be used in AGD management. However, the
consequences of modifying the intensity of freshwater treatment regimes on
freshwater tolerance evolution in N. perurans populations require careful
consideration.
PMID- 29938801
TI - Mathematical Disease Progression Modeling in Type 2/3 Spinal Muscular Atrophy.
AB - INTRODUCTION: We propose a mathematical model to empirically describe spinal
muscular atrophy (SMA) progression assessed by the 3 domains of the motor
function measure (MFM) scale. The model implements development and deterioration
of muscle function. METHODS: Nonlinear mixed-effects modeling was applied to data
from 2 observational studies and 1 prospective clinical efficacy study comprising
190 healthy participants and 277 patients with type 2/3 SMA. RESULTS: The model
evidenced correlations between parameter estimates for different MFM domains.
Slower development in MFM domain D1 (standing and transfers) was associated with
faster deterioration for MFM domains D2 (proximal and axial motricity) and D3
(distal motor function). DISCUSSION: The model describes all individual data
well, although sparseness and variability of observational data prevented
numerically stable estimation of parameters. Treatment duration in clinical
studies was too limited to determine a proper drug-effect model that could
differentiate between symptomatic and disease modifying effects. Muscle Nerve 58:
528-535, 2018.
PMID- 29938800
TI - High V-PPase activity is beneficial under high salt loads, but detrimental
without salinity.
AB - The membrane-bound proton-pumping pyrophosphatase (V-PPase), together with the V
type H+ -ATPase, generates the proton motive force that drives vacuolar membrane
solute transport. Transgenic plants constitutively overexpressing V-PPases were
shown to have improved salinity tolerance, but the relative impact of increasing
PPi hydrolysis and proton-pumping functions has yet to be dissected. For a better
understanding of the molecular processes underlying V-PPase-dependent salt
tolerance, we transiently overexpressed the pyrophosphate-driven proton pump
(NbVHP) in Nicotiana benthamiana leaves and studied its functional properties in
relation to salt treatment by primarily using patch-clamp, impalement electrodes
and pH imaging. NbVHP overexpression led to higher vacuolar proton currents and
vacuolar acidification. After 3 d in salt-untreated conditions, V-PPase
overexpressing leaves showed a drop in photosynthetic capacity, plasma membrane
depolarization and eventual leaf necrosis. Salt, however, rescued NbVHP
hyperactive cells from cell death. Furthermore, a salt-induced rise in V-PPase
but not of V-ATPase pump currents was detected in nontransformed plants. The
results indicate that under normal growth conditions, plants need to regulate the
V-PPase pump activity to avoid hyperactivity and its negative feedback on cell
viability. Nonetheless, V-PPase proton pump function becomes increasingly
important under salt stress for generating the pH gradient necessary for vacuolar
proton-coupled Na+ sequestration.
PMID- 29938802
TI - Accelerated tattoo removal with acoustic shock wave therapy in conjunction with a
picosecond laser.
AB - BACKGROUND: Conventional tattoo removal consists of single-pass treatments,
spaced 7-8 weeks apart, for a total of 7-10 sessions. A major limiting factor of
this procedure is the development of cavitation bubbles and vacuoles within the
epidermis and dermis that result from the rapid heating of tattoo particles by
the laser. While multiple-pass methods using the R20 protocol or the PFD patch
enhance tattoo removal through epidermal clearance, they have no effect on deep
intradermal pigment associated vacuoles that arise from treatment with lasers
such as the Q-switched laser. METHODS: A 28-year-old female with Fitzpatrick skin
Type V presented for treatment of a 6-year-old professional black tattoo on the
left ventral wrist. She underwent three treatment sessions at 6-8 week intervals
using a commercial 1,064-nm picosecond Nd:YAG laser (PicoWay; Candela, Wayland,
MA) and a perfluorodecalin (PFD) patch (Merz; Raleigh, NC). At each treatment
session, she received two passes with 1,064-nm, 4-mm spot size, a fluence ranging
from 2.8 to 3.2 J/cm2 and a laser repetition rate of 2 Hz. Between laser passes
and following the final laser pass, the medial portion of the tattoo was treated
with acoustic shock wave therapy (ASWT) using the Zwave device (Zimmer Medizin
Systems; Irvine, CA) with 90 mJ, 22 Hz, and 1,200 pulses. RESULTS: After three
treatment sessions, there was 80% clearance of the medial portion of the tattoo
that received the ASWT compared with 60% clearance of the lateral portion of the
tattoo that was treated with the picosecond 1,064-nm Nd:YAG laser and PFD patch
alone. In the days following each treatment session, the patient noted
consistently less edema, erythema and epidermal crusting on the portion of the
tattoo that received the ASWT. CONCLUSION: We report a case of 80% tattoo
clearance with ASWT in a patient with Fitzpatrick type V skin compared with 60%
clearance with the picosecond 1064-nm Nd:YAG laser and PFD patch alone. The
concurrent use of the PFD patch, which facilitated multi-pass treatments, may
have also increased tattoo fading in this patient. ASWT may enhance tattoo
clearance by increasing lymphatic drainage and increasing metabolic activity in
the treated area, thereby accelerating the clearance of dermal pigment vacuoles
produced by the picosecond laser and minimizing epidermal side effects such as
erythema, edema, and crusting. Lasers Surg. Med. 50:890-892, 2018. (c) 2018 Wiley
Periodicals, Inc.
PMID- 29938803
TI - Reactivity of recombinant Toxocara canis TES-30/120 in experimentally infected
mice.
AB - AIM: While the use of recombinant antigens is being widely investigated in the
diagnosis of human toxocariasis, relatively little attention has been given to
animal diagnostic models. For this reason, this study aimed to investigate the
diagnosis potential of Toxocara canis TES-30 and TES-120 recombinant antigens in
mice, the animal model for toxocariasis studies. METHODS AND RESULTS: Serum
samples obtained from mice infected with T. canis or Toxocara cati were tested by
indirect ELISA using T. canis TES-30 and TES-120 recombinant antigens produced in
Escherichia coli. 90% of the samples reacted with rTES-30, whereas there was
almost no reactivity with rTES-120. CONCLUSION: Despite rTES-120 being a good
antigen for diagnosis in humans, it could not reproduce its reactivity in this
animal model. As rTES-30 has good reactivity in mice, it is a valuable tool for
diagnosis.
PMID- 29938804
TI - Potential use of soilborne lytic Podoviridae phage as a biocontrol agent against
Ralstonia solanacearum.
AB - A new podovirus RsPod1EGY Ralstonia phage (GenBank accession no MG711516) with a
specific action against R. solanacearum phylotype IIa, sequevar I (race 3, biovar
2) was isolated from Egyptian soil. The potential efficacy of the isolated phage
to be used as biocontrol agent was evaluated in vitro and under greenhouse
conditions. The podovirus phage produced a plaque size of 3.0-4.0 mm in diameter
and completed its infection cycle in 180 min after infection with a burst size of
~27 virions per infected cell. On the basis of restriction endonuclease analysis,
the genome size of the phage was about 41 kb of double-stranded DNA. In vitro
studies showed that RsPod1EGY is stable at higher temperatures (up to 60 degrees
C), and at a wide pH range (5-9). SDS-PAGE analysis indicated the major
structural protein to be approximately 32 kDa. Bacteriolytic activity of
RsPod1EGY against R. solanacearum was detected at different multiplicity of
infection (MOI). RsPod1EGY proved to be effective in reduction and prevention of
formation of surface polysaccharides of R. solanacearum, during the exponential
growth phase of the latter. Interestingly, RsPod1EGY was effective in suppression
of R. solanacearum under greenhouse conditions. All Phage-treated tomato plants
showed no wilt symptoms or any latent infection during the experimental period,
whereas all untreated plants have wilted by 10 days post-infection. The lytic
stability of RsPod1EGY phage at higher temperature as well as its effective
suppression of wilting symptoms under greenhouse conditions would contribute to
biocontrol the bacterial wilt disease in Egypt under field conditions.
PMID- 29938806
TI - May the Fittest Protein Evolve: Favoring the Plant-Specific Origin and Expansion
of NAC Transcription Factors.
AB - Plant-specific NAC transcription factors (TFs) evolve during the transition from
aquatic to terrestrial plant life and are amplified to become one of the biggest
TF families. This is because they regulate genes involved in water conductance
and cell support. They also control flower and fruit formation. The review
presented here focuses on various properties, regulatory intricacies, and
developmental roles of NAC family members. Processes controlled by NACs depend
majorly on their transcriptional properties. NACs can function as both activators
and/or repressors. Additionally, their homo/hetero dimerization abilities can
also affect DNA binding and activation properties. The active protein levels are
dependent on the regulatory cascades. Because NACs regulate both development and
stress responses in plants, in-depth knowledge about them has the potential to
help guide future crop improvement studies.
PMID- 29938805
TI - Feather degrading, phytostimulating, and biocontrol potential of native
actinobacteria from North Eastern Indian Himalayan Region.
AB - Twelve actinobacterial strains were isolated from tomato rhizospheric soil from
Manipur, a state in North East Indian Himalayan Region and screened for
keratinolytic and plant growth promoting traits. Nine promising isolates were
identified as Streptomyces species using partial 16S rRNA gene sequencing. Among
the seven isolates showing chicken feather degradation activity, three
keratinolytic strains RCM-SSR-2, -6, and -12 were found to be the most efficient
feather degrading strains achieving 90% feather weight loss within 48 h of
incubation. They also showed maximum keratinase and soluble peptide production.
Strain RCM-SSR-2, -5, -6, -8, and -11 showed positive results for all plant
growth promoting traits tested. Maximum indole-3-acetic acid production was
exhibited by RCM-SSR-6. Strain RCM-SSR-1, -2, -5, -6, -9, and -11 showed
antagonistic activity against three important plant pathogens. Feather
hydrolysate of RCM-SSR-6 was also evaluated for in vitro seed germination test
using garden pea seeds. Higher concentration of feather protein hydrolysate (3 mg
ml-1 ) inhibited shoot and root length of the germinating embryo. However, lower
concentration (0.01 mg ml-1 ) of feather protein hydrolysate promoted seed
germination. Among the 12 strains, four isolates namely RCM-SSR-1, -2, -5, and -6
were found to be promising as multi-traits plant growth promoting rhizobacteria
for development of organic fertilizer, phytostimulator, and biocontrol agents.
PMID- 29938807
TI - Isolation and molecular characterization of biosurfactant producing yeasts from
the soil samples contaminated with petroleum derivatives.
AB - In this study, 65 yeast strains were isolated from different environmental
samples contaminated with various petroleum hydrocarbons such as activated
sludges and soil samples from automobile workshops. The yeast isolates were
tested for biosurfactant production using various screening methods such as
parafilm M test, oil displacement assay, drop collapse assay, determination of
surface tension reduction, and emulsification index. Nineteen of the isolates
were found positive for biosurfactant production and their molecular
characterizations were carried out by sequencing analysis of the ITS1-5.8S-ITS2
region and D1/D2 domain of 26S rDNA. The results indicated that these strains
were from a wide range of yeast genera including Rhodotorula, Candida, Yarrowia,
Geotrichum, Galactomyces, and Cystobasidium. The studies to determine the
emulsification index revealed that the biosurfactants produced by Yarrowia
lipolytica strains (TEMGS33, TEMOS12, and TEMOS14) and Apiotrichum loubieri
strain (TEMOS16) were the most potent and capable of forming stable emulsions
with emulsion index (E24 ) up to 68%. In addition, quantitative measurements of
the surface tension reduction of the biosurfactants produced by these strains
were carried out by Du Nouy ring method. Biosurfactants produced from Yarrowia
lipolytica strain TEMGS33 and Apiotrichum loubieri strain TEMOS16 gave the best
results reducing the surface tension to 34.7 +/- 1.15 and 35.3 +/- 0.55 mN m-1 ,
respectively. Based on these data, biosurfactants from Yarrawia lipolytica
strains (TEMGS33, TEMOS12, and TEMOS14) and Apiotrichum loubieri strain (TEMOS16)
showed promising results and might be implemented in numerous industrial fields
such as bioremediation and food industry.
PMID- 29938808
TI - First detection of yellow head virus genotype 3 (YHV-3) in cultured Penaeus
monodon, mainland China.
PMID- 29938809
TI - Antimicrobial-producing Pseudoalteromonas from the marine environment of Panama
shows a high phylogenetic diversity and clonal structure.
AB - Pseudoalteromonas is a genus of marine bacteria often found in association with
other organisms. Although several studies have examined Pseudoalteromonas
diversity and their antimicrobial activity, its diversity in tropical
environments is largely unexplored. We investigated the diversity of
Pseudoalteromonas in marine environments of Panama using a multilocus
phylogenetic approach. Furthermore we tested their antimicrobial capacity and
evaluated the effect of recombination and mutation in shaping their phylogenetic
relationships. The reconstruction of clonal relationships among 78 strains
including 15 reference Pseudoalteromonas species revealed 43 clonal lineages,
divided in pigmented and non-pigmented strains. In total, 39 strains displayed
moderate to high activity against Gram-positive and Gram-negative bacteria and
fungi. Linkage disequilibrium analyses showed that the Pseudoalteromonas strains
of Panama have a highly clonal structure and that, although present,
recombination is not frequent enough to break the association among alleles. This
clonal structure is in contrast to the high rates of recombination generally
reported for aquatic and marine bacteria. We propose that this structure is
likely due to the symbiotic association with marine invertebrates of most strains
analyzed. Our results also show that there are several putative new species of
Pseudoalteromonas in Panama to be described.
PMID- 29938810
TI - Cells in the Non-Uniform Magnetic World: How Cells Respond to High-Gradient
Magnetic Fields.
AB - Imagine cells that live in a high-gradient magnetic field (HGMF). Through what
mechanisms do the cells sense a non-uniform magnetic field and how such a field
changes the cell fate? We show that magnetic forces generated by HGMFs can be
comparable to intracellular forces and therefore may be capable of altering the
functionality of an individual cell and tissues in unprecedented ways. We
identify the cellular effectors of such fields and propose novel routes in cell
biology predicting new biological effects such as magnetic control of cell-to
cell communication and vesicle transport, magnetic control of intracellular ROS
levels, magnetically induced differentiation of stem cells, magnetically assisted
cell division, or prevention of cells from dividing. On the basis of experimental
facts and theoretical modeling we reveal timescales of cellular responses to high
gradient magnetic fields and suggest an explicit dependence of the cell response
time on the magnitude of the magnetic field gradient.
PMID- 29938811
TI - Interspecific and sexual differences in riverine distribution of tropical eels
Anguilla spp.
AB - A total of 261 individuals of the four tropical eel species, Anguilla
celebesensis, Anguilla marmorata, Anguilla bicolor pacifica and Anguilla
interioris, were collected from 12 locations around Sulawesi Island, Indonesia,
to gain knowledge about the riverine distribution of tropical eels. Anguilla
marmorata was predominant in the lower reaches of Poso River (94.4% of total eel
catch in the sampling area), Poso Lake (93.3%), three small inlet rivers of
Tomini Bay (100%) and Laa River (92.3%). Anguilla celebesensis occurred
frequently in the inlet rivers of Poso Lake (63.5%). Anguilla bicolor pacifica
and Anguilla interioris were rare (1.5 and 0.4%, respectively). Otolith Sr:Ca
ratio electron-probe micro analysis (EPMA) for individual migratory histories
revealed that 15 A. celebesensis caught in Poso Lake and its inlet rivers were
categorized into 14 river eels (Sr:Ca < 2.5) showing upstream migration seemingly
at their elver stage and only one sea eel (Sr:Ca >= 6.0) that stayed in the
marine habitat for the majority of its life after recruiting to Sulawesi Island
before its late upstream migration. In A. marmorata, 19 examined eels from Poso
Lake and its inlet rivers were all river eels, while 17 eels from the lower
reaches of Poso River were two river eels, six sea eels and nine estuarine eels
(2.5 <= Sr:Ca < 6.0) that mostly lived in the brackish water. The sex ratio of A.
celebesensis was highly skewed towards a dominance of females (99%). In A.
marmorata, females were predominant in Poso Lake (95.2%), its inlet rivers
(94.7%) and Laa River (100%), while males were more frequent in the lower reaches
of Poso River (76.5%) and small inlet rivers of Tomini Bay (94.1%). These results
indicate that the riverine distribution pattern of tropical eels differs among
species and between sexes.
PMID- 29938812
TI - The effects of a small hydropower scheme on the migratory behaviour of Atlantic
salmon Salmo salar smolts.
AB - The potential effects of a hydropower scheme on the migratory behaviour of
Atlantic salmon Salmo salar smolts was studied on the River Frome, southern
England. The potential delay to migration at the intake of the hydropower scheme
was assessed, together with the effects of passage through the turbine on the
temporal and spatial migration of the fish in the river and estuary. The
migratory behaviour of the emigrating S. salar smolts was monitored using
miniature acoustic transmitters and an array of acoustic receivers positioned at
the hydropower scheme and in the river and estuary. The majority of the smolts
bypassed the hydropower scheme with only 8.1% of the fish moving downstream
through the turbine. Movement was nocturnal and occurred during elevated river
flows. There was no apparent delay at the turbine intake or at the adjacent weir.
The subsequent migration of all smolts through the estuary of the River Frome
occurred during both day and night and there was a distinct ebb-tide migration
through the estuary and into the coastal zone. There was no difference in the
rate of migration between smolts that moved through the turbine or over the weir.
The detection of smolts during both the freshwater migration and the transition
from the freshwater to the marine environments was high (91.8 and 73.3%,
respectively). A laboratory investigation on the de-scaling of smolts indicated
that removal of 1, 5 and 10% of scales had no significant effect on saltwater
survival or the measured physiological parameters (gill Na+ -K+ -ATPase activity,
plasma osmolality and chloride concentrations). Smolt passage through the turbine
was assessed and resulted in either no damage to the integument or scale loss or
between 20 and 80% of total body area of recaptured smolts. It is estimated that
1.53% of the smolt population would suffer significant damage after passage
through the turbine. The implications of the hydropower scheme on the population
of salmon in the River Frome are discussed.
PMID- 29938813
TI - Fibromyalgia and small-fiber polyneuropathy: What's in a name?
PMID- 29938814
TI - Fentanyls and the safety of first responders: Science and recommendations.
AB - Opioids have many beneficial uses in medicine, but, taken inappropriately, they
can cause life-threatening health effects. The increasing use of physician
prescribed and illicit opioids, including highly potent fentanyl and its analogs,
have contributed to a significant increase in opioid-related drug overdoses in
the United States, leading to a public health emergency. There have been a number
of reports describing adverse health effects experienced by police officers, fire
fighter emergency medical services providers, and private sector ambulance
personnel when responding to drug overdose incidents. Several sets of exposure
prevention recommendations for first responders are available from government and
the private sector. Understanding the scientific basis for these recommendations,
increasing awareness by responders of the potential risks associated with opioid
exposure during a response, and educating responders about safe work practices
when exposure to opioids is suspected or confirmed are all critical prevention
measures that can keep first responders safe.
PMID- 29938815
TI - Mathematical modeling of intracrine androgen metabolism in prostate cancer:
Methodological aspects.
AB - BACKGROUND: Progression of castration-recurrent/resistant prostate cancer (CRPC)
relies in part on dihydrotestosterone derived from intratumoral androgen
metabolism. Mathematical modeling provides a valuable tool for studies of
androgen metabolism in CRPC. This modeling approach integrates existing knowledge
about complex biologic systems and provides a means of interrogating the effects
of various interventions. We sought to model a single reaction in the androgen
biosynthesis network, namely the oxidation of androsterone (AND) to
androstanedione (5alpha-dione) by four 3alpha-oxidoreductase enzymes, as an
initial effort to establish the feasibility of our modeling approach. METHODS:
Models were constructed for two cell culture systems, a non-prostate cancer cell
line (CV-1) and a prostate cancer cell line (LAPC-4), using the SimBiology app
(version 5.3) in MATLAB (version 8.6). The models included components for
substrate (AND), product (5alpha-dione), each of the four enzymes, and each of
the four enzyme-substrate complexes. Each enzymatic reaction consisted of a
reversible enzyme-substrate binding step and an irreversible catalysis step.
Rates of change for each component were described using ordinary differential
equations. RESULTS: Mathematical models were developed with model parameter
values derived from literature sources or from existing experimental data, which
included gene expression measurements and substrate and product concentrations
determined using liquid chromatography-tandem mass spectrometry. The models for
both cell lines adequately described substrate and product concentrations
observed after 12 h treatment with AND. CONCLUSIONS: This modeling approach
represents an adaptable, extensible and mechanistic framework that reflects
androgen metabolism. The models can be expanded systematically to describe the
complex androgen metabolic pathways important for study of novel therapies for
CRPC.
PMID- 29938816
TI - A class of semiparametric tests of treatment effect robust to confounder
measurement error.
AB - When assessing the presence of an exposure causal effect on a given outcome,
measurement error of a confounder can inflate the type I error rate of a
treatment effect in even the simplest of settings. In this paper, we develop a
large class of semiparametric test statistics of an exposure causal effect, which
are completely robust to additive unbiased measurement error of a subset of
confounders. A unique and appealing feature of our proposed methodology is that
it requires no external information such as validation data or replicates of
error-prone confounders. We present a doubly robust form of this test that
requires the exposure mean model to be linear in the mismeasured confounders, and
only one of two models involving error-free confounders to be correctly specified
for the resulting test statistic to have correct type I error rate. We
demonstrate validity within our class of test statistics through simulation
studies. We apply the methods to a multi-US-city time-series data set to test for
an effect of temperature on mortality while adjusting for atmospheric particulate
matter with diameter of 2.5 micrometres or less, which is known to be measured
with error.
PMID- 29938817
TI - Bayesian design of a survival trial with a cured fraction using historical data.
AB - In this paper, we develop a general Bayesian clinical trial design methodology,
tailored for time-to-event trials with a cured fraction in scenarios where a
previously completed clinical trial is available to inform the design and
analysis of the new trial. Our methodology provides a conceptually appealing and
computationally feasible framework that allows one to construct a fixed,
maximally informative prior a priori while simultaneously identifying the minimum
sample size required for the new trial so that the design has high power and
reasonable type I error control from a Bayesian perspective. This strategy is
particularly well suited for scenarios where adaptive borrowing approaches are
not practical due to the nature of the trial, complexity of the model, or the
source of the prior information. Control of a Bayesian type I error rate offers a
sensible balance between wanting to use high-quality information in the design
and analysis of future trials while still controlling type I errors in an
equitable way. Moreover, sample size determination based on our Bayesian view of
power can lead to a more adequately sized trial by virtue of taking into account
all the uncertainty in the treatment effect. We demonstrate our methodology by
designing a cancer clinical trial in high-risk melanoma.
PMID- 29938818
TI - Heterogeneity in Short-Term Suicidal Ideation Trajectories: Predictors of and
Projections to Suicidal Behavior.
AB - OBJECTIVE: Little is known about suicidal ideation stability, including whether
stability is heterogeneous or homogeneous between individuals. Studies of this
kind are necessary to understand the progression from suicidal ideation to
action. METHOD: This study examined suicidal ideation trajectories, using growth
mixture modeling, in a sample of 359 past/current military service members (M age
= 32.1 years, SD = 7.7; 88.3% male). Self-reported suicidal ideation information
was collected at baseline and follow-up sessions at months 1, 3, 6, and 12.
Following extraction of the best-fitting solution, predictors of trajectory
status were examined and trajectory status was used to predict suicidal behavior
between baseline and month 12 assessments. RESULTS: Results revealed four
trajectories, Low-Stable (n = 125), Moderate-Stable (n = 101), High-Stable (n =
76), and High-Rapidly Declining (n = 57). In general, the High-Stable trajectory
had the highest levels of perceived burdensomeness, thwarted belongingness, PTSD
symptoms, and drug use. The High- and Moderate-Stable trajectories had the
highest rates of suicidal behavior between baseline and month 12. CONCLUSIONS:
Suicidal ideation, even in individuals with elevated ideation, is not a
homogeneous construct over time. Stability of suicidal ideation might be an
important risk factor, even if ideation is only moderately elevated.
PMID- 29938819
TI - Essential oils rich in monoterpenes are unsuitable as additives to boar semen
extender.
AB - Despite the development of efficient boar semen extenders, there is still room
for improvement of new formulas using new molecules that could increase
fertilisation outcomes and substitute cryoprotectants and antibiotics. The goal
of this work was to evaluate if the essential oils from the leaves of Myrrhinium
atropurpureum and Cymbopogon citratus are suitable as additives in boar semen
extender. The major compounds found in the essential oils from M. atropurpureum
were 1,8-cineole (37.37%) and terpinolene (19.18%); and geranial (49.8%) and
neral (33.24%) in essential oil of C. citratus. The addition of 1% and 0.1% of
both essential oils to extended semen had immediate spermicidal effects (p <
0.05). Lower concentrations were tested and no cytotoxic effect was observed when
M. atropurpureum essential oil was added at 0.001%. Differently, essential oil
from C. citratus reduced sperm motility, membrane functionality and integrity and
mitochondrial membrane potential even in concentrations as low as 0.001%. Also,
addition of essential oils in low concentrations had no inhibitory effect against
Escherichia coli and Pseudomonas aeruginosa growth. We conclude that the
essential oils from C. citratus and M. atropurpureum, rich in monoterpenes, are
cytotoxic to swine spermatozoa, therefore unsuitable as semen extender additives.
PMID- 29938820
TI - Oral health and performance impacts in elite and professional athletes.
AB - OBJECTIVES: To measure dental caries, erosive tooth wear (ETW), periodontal
health, self-reported oral health problems and performance impacts in a
representative sample of UK elite athletes from different sports using
standardized conditions clearly defined clinical indices and a measure of impact
on performance with evidence of validity in sport. METHODS: Cross-sectional
study, with single, calibrated examiner, conducted in the local facilities of
elite and professional UK athletes (UCL ethics number 6388/001). Main oral
measures: dental caries (ICDAS), erosive tooth wear (BEWE), periodontal health
(BPE) and athlete-reported performance impacts. RESULTS: We recruited 352
athletes from eleven sports. The mean age was 25 years (range 18-39), and 67.0%
were male. We found caries (ICDAS code >=3) in 49.1% of athletes, ETW (BEWE score
of >=7) in 41.4%, gingival bleeding on probing/presence of calculus (BPE score 1
or 2) in 77.0% and pocket probing depths of at least 4 mm (BPE score 3 or 4) in a
further 21.6%. One in five athletes reported previous wisdom teeth problems. The
odds of having caries were 2.4 times greater in team sport than endurance sport
(95% CI 1.3-3.2). The odds of having erosion were 2.0 times greater in team sport
than endurance sport (95% CI 1.3-3.1). Overall, 32.0% athletes reported an oral
health-related impact on sport performance: oral pain (29.9%), difficulty
participating in normal training and competition (9.0%), performance affected
(5.8%) and reduction in training volume (3.8%). Other impacts were difficulty
with eating (34.6%), relaxing (15.1%) and smiling (17.2%). Several oral health
problems were associated with performance impacts. CONCLUSIONS: This is the first
large representative sample study of oral health in athletes from different
sports at elite level. Although experience of oral disease differs by sport, the
prevalence, in UK elite and professional athletes, is substantial, with common
self-reported performance impacts. Regular screening and use of effective oral
health promotion strategies may minimize performance impacts from poor oral
health.
PMID- 29938821
TI - Effects of microsurgical varicocelectomy on semen analysis and sperm function
tests in patients with different grades of varicocele: Role of sperm functional
tests in evaluation of treatments outcome.
AB - It seems that varicocele play a role in male infertility, as such, their
prevalence increases from 15% in the normal population to 80% in secondary
infertility subjects. Varicoceles may have negative effects on semen quality. Our
goal was to assess the effects of microsurgical varicocelectomy on semen analysis
and sperm functional tests in men with different grades of varicoceles. Thirty
infertile men with different grades of varicoceles (grades 1 to 3) were enrolled
in our study. Semen quality was assessed by semen analysis according to the WHO
guideline (WHO, 1999) and four different sperm functional tests (aniline blue,
toluidine blue, chromomycin A3 and TUNEL test) were carried out before and 3
months after microsurgical varicocelectomy (M-varicocelectomy). When considered
all three grades together, we showed that M-varicocelectomy had statistically
significant effects on all four types of sperm functional tests (p value<0.05).
It also had positive effects on conventional semen parameters, although the
effects were not statistically significant for some parameters (for example sperm
count). When analysed separately (based on varicocele grades) the surgery,
although caused improvements in semen quality, but may have more statistically
significant effects on patients with varicocele of higher grade. In addition, in
varicocele of lower grade (for example grade 2), sperm function test may be a
better predictor of surgical success than the conventional semen analysis. Thus,
we show that not only M-varicocelectomy has significant positive effect on semen
quality but also if sperm functional tests become more affordable in the future,
because they yield more precise results, their use in daily practice may increase
significantly in patients with varicoceles.
PMID- 29938822
TI - Clinical features of haematospermia associated with seminal vesicle calculi
versus posterior urethral haemangioma.
AB - To compare the clinical features of seminal vesicle calculi(SVC) versus posterior
urethral haemangioma(PUH) to assist urologists in differentiating and diagnosing
the causes of haematospermia. Patients with SVC or PUH were included. Patient
age, disease duration, hospital stay, operation time, symptoms, surgical
approach, pathological results and postoperative complications were recorded. A
total of seven patients with SVC and 15 patients with PUH involved have an
average age of 34.1 and 44.5 years separately. Patients with SVC complained of
recurrent haematospermia; patients with PUH complained of recurrent
haematospermia and urethral opening bleeding after sexual arousal. SVC manifested
as a dark red blood-semen mixture with ejaculation pain and no blood clots; the
condition could improve after anti-infective treatment. PUH manifested as no
visible blood-semen mixture, bright red semen with blood clots and no ejaculation
pain; the condition did not respond to anti-infective treatment. SVC was treated
with holmium laser lithotripsy under a transurethral seminal vesiculoscopy. PUH
was treated with transurethral resection and fulguration. Postoperative follow-up
showed that the clinical symptoms gradually disappeared, with no postoperative
complications. Both SVC and PUH can result in recurrent haematospermia.
Therefore, urologists should treat haematospermia differently according to the
cause.
PMID- 29938823
TI - Mothers' perspectives of the experience and impact of caring for their child with
a life-limiting neurodevelopmental disability.
AB - BACKGROUND: This study explored mothers' perspectives of the experiences and
impact on themselves and their family when their child has a life-limiting
neurodevelopmental disability. METHODS: Twelve mothers were interviewed and
topics included mothers' experiences of caring, the impact on themselves and
their family of care provision, and the management of day-to-day life. Data were
analysed using thematic analysis. RESULTS: Four themes were identified. "Starting
Out" relates to mothers' experiences of the birth of their child and the
aftermath. "Keeping the Show on the Road" describes the strategies families
employ to manage life day to day and the resources they use. "Shouldering the
Burden" describes the range of physical, psychological, and social consequences
of the situation for mothers and the family. "The Bigger Picture" relates to the
world outside the family and how this is navigated. CONCLUSIONS: Findings suggest
mothers' overall experiences are characterized by a constant struggle, with
evidence of negative impacts on family life, though there is also evidence of
resilience and coping. Implications regarding the provision of services are
discussed.
PMID- 29938824
TI - Investigating US medical students' motivation to respond to lapses in
professionalism.
AB - CONTEXT: As unprofessional behaviour in physicians can compromise patient safety,
all physicians should be willing and able to respond to lapses in
professionalism. Although students endorse an obligation to respond to lapses,
they experience difficulties in doing so. If medical educators knew how students
respond and why they choose certain responses, they could support students in
responding appropriately. OBJECTIVES: The aim of this study was to describe
medical students' responses to professionalism lapses in peers and faculty staff,
and to understand students' motivation for responding or not responding. METHODS:
We conducted an explorative, qualitative study using template analysis, in which
three researchers independently coded transcripts of semi-structured, face-to
face interviews. We purposefully sampled 18 student representatives convening at
a medical education conference. Preliminary open coding of a data subset yielded
an initial template, which was applied to further data and modified as necessary.
All transcripts were coded using the final template. Finally, three sensitising
concepts from the Expectancy-Value-Cost model were used to map participants'
responses. RESULTS: Students mentioned having observed lapses in professionalism
in both faculty staff and peers. Students' responses to these lapses were
avoiding, addressing, reporting or initiating policy change. Generally, students
were not motivated to respond if they did not know how to respond, if they
believed responding was futile and if they feared retaliation. Students were
motivated to respond if they were personally affected, if they perceived the
individual as approachable and if they thought that the whole group of students
could benefit from their actions. Expectancy of success, value and costs each
appeared to be influenced by (inter)personal and system factors. CONCLUSIONS: The
Expectancy-Value-Cost model effectively explains students' motivation for
responding to lapses. The (inter)personal and system factors influencing
students' motivation to respond are modifiable and can be used by medical
educators to enhance students' motivation to respond to lapses in professionalism
observed in medical school.
PMID- 29938825
TI - Maternal insulin resistance, triglycerides and cord blood insulin are not
determinants of offspring growth and adiposity up to 5 years: a follow-up study.
AB - AIMS: Metabolic dysregulation in utero may influence fetal metabolism and early
growth. We previously investigated relationships between maternal indices of
glucose homeostasis and triglycerides as well as cord blood insulin with
offspring anthropometry up to 2 years. The aim of this analysis was to follow
these relationships up to the age of 5 years. METHODS: Associations between
maternal metabolic variables of glucose and lipid metabolism measured at 32
weeks' gestation and cord blood insulin with growth and body composition of 162
offspring aged 3-5 years were explored. Both indirect (i.e. body weight, BMI
percentiles, sum of four skinfold thicknesses) and direct (i.e. ultrasonography,
magnetic resonance imaging in a subgroup) measurement techniques were employed.
RESULTS: Maternal metabolic indices were largely unrelated to child body
composition. Cord blood insulin was negatively associated with fat mass and lean
body mass at 3 years in unadjusted analyses, and the sum of four skinfold
thicknesses and body fat percentage in adjusted analyses, whereas the association
with lean body mass was no longer observed. An inverse relationship between cord
blood insulin and weight gain up to 5 years was observed in girls only with small
effect sizes. CONCLUSIONS: Results from this follow-up do not provide convincing
evidence that these markers are independently related to offspring growth and
adiposity in early childhood. Although cord blood insulin was weakly inversely
related to weight gain in girls at 5 years, we cannot conclude that the observed
changes in outcomes are clinically meaningful. (Clinical Trials Registry No:
NCT00362089).
PMID- 29938826
TI - Visual, musculoskeletal and balance symptoms in individuals with visual
impairment.
AB - BACKGROUND: Visual impairment is globally among the most prevalent disabilities.
Research concerning the health consequences of visual deficits is challenged by
confounding effects of age, because visual impairment becomes more prevalent with
age. This study investigates the influence of visual deficits on visual,
musculoskeletal and balance symptoms in adults with and without visual
impairment, while controlling for age effects. METHODS: Thirty-nine patients with
visual impairment, aged 18-72 years, were compared to 37 age-matched controls
with normal vision, allocated to two age groups: < 45 and >= 45 years. Self
reported symptoms were measured using the Visual, Musculoskeletal and Balance
Symptoms Questionnaire and compared with demographic and optometric variables.
RESULTS: In total, patients with visual impairment reported more symptoms than
age-matched normally sighted controls. Younger adults in the control group were
almost free from symptoms, whereas younger adults with visual impairment reported
levels of symptoms equal to older adults with visual impairment. Multiple
logistic regression modelling identified use of eyeglasses, magnifying aids and
presence of anisometropia to be the most influential risk factors for reporting
visual, musculoskeletal and balance symptoms, with accentuated influence on
balance symptoms. CONCLUSIONS: People with visual impairments and people with age
related normal visual deficits are both predisposed to report visual,
musculoskeletal and balance symptoms relative to people without visual defects or
need for eye-wear correction. Age-related variations in symptoms were observed in
the control groups but not in the visual impairment groups, with younger visual
impairment patients reporting as many symptoms as older visual impairment
patients. These findings indicate a need for a wider interdisciplinary
perspective on eye care concerning people with visual impairment and people with
need for habitual daily use of eye wear correction.
PMID- 29938827
TI - Pembrolizumab-induced sarcoidal infusion site reaction.
PMID- 29938828
TI - The safety and feasibility of minimal invasive plate osteosynthesis (MIPO) of the
posterior aspect of the humerus: A cadaveric study.
AB - The aim of this study was to determine the feasibility of applying MIPO of the
humerus via the posterior approach and to observe the tension of the radial nerve
in different elbow positions. Two separate incisions were made on the posterior
aspect of the humerus in ten fresh cadavers (20 humeri). The radial nerve was
identified at the proximal incision and the distances through which the nerve
could be elevated from the bone with the elbow in flexion and extension were
measured. A 10-hole extra-articular distal humeral locking compression plate was
inserted and fixed through the submuscular tunnel. The tunnel was then explored
to identify any entrapment of the radial nerve and to observe the anatomical
relationship of the radial nerve to the plate and bone. There was no entrapment
of the radial nerve or its branches. The distances through which the radial nerve
could be elevated were greater with the elbow in extension than in flexion (P <
0.01). The radial nerve crossed the medial and lateral borders of the posterior
surface of the humerus at 80.1-132 mm (average 104.7 mm) and 116.6-175.5 mm
(average 142.7 mm) of its total length, respectively. The axillary nerve was
located at 38.7-61.7 mm (average 47.9 mm) of total humeral length. MIPO of the
humerus using the posterior approach is an alternative option for treating distal
humeral shaft fracture. The risk of radial nerve injury can be minimized by
careful dissection in the proximal incision. Clin. Anat., 2018. (c) 2018 Wiley
Periodicals, Inc.
PMID- 29938829
TI - MicroRNA-383 acts as a tumor suppressor in colorectal cancer by modulating
CREPT/RPRD1B expression.
AB - CREPT (Cell-cycle-related and expression-elevated protein in tumor)/RPRD1B, a
novel protein that enhances the transcription of Cyclin D1 to promote cell
proliferation during tumorigenesis, was demonstrated highly expressed in most of
tumors. However, it remains unclear how CREPT is regulated in colorectal cancers.
In this study, we report that miR-383 negatively regulates CREPT expression. We
observed that CREPT was up-regulated but the expression of miR-383 was down
regulated in both colon cancer cell lines and colon tumor tissues. Intriguingly,
we found that enforced expression of miR-383 inhibited the expression of CREPT at
both the mRNA and protein level. Using a luciferase reporter, we showed that miR
383 targeted the 3'-UTR of CREPT mRNA directly. Consistently we observed that
over expression of miR-383 shortened the half-life of CREPT mRNA in varieties of
colorectal cancer cells. Furthermore, restoration of miR-383 inhibited cell
growth and colony formation of colon cancer cells accompanied by inhibition of
expression of CREPT and related downstream genes. Finally, we demonstrated that
stable over expression of miR-383 in colon cancer cells decreased the growth of
the tumors. Our results revealed that the abundant expression of CREPT in
colorectal cancers is attributed to the decreased level of miR-383. This study
shed a new light on the potential therapeutic therapy strategy for colorectal
cancers using introduced miRNA.
PMID- 29938830
TI - Topographical study of the connections of the rami communicantes from the first
to the fifth thoracic sympathetic ganglia.
AB - This study investigated the morphological variations and histological patterns of
the rami communicantes (RCs) arising from the first to the fifth thoracic
sympathetic ganglia, and considered the clinical significance of these
variations. Fifty upper thoracic portions from 26 adult Korean cadavers were used
in this study. There were 731 RCs arising from the first to the fifth thoracic
sympathetic ganglia. They were classified into three types depending on the
connection between the sympathetic ganglion and the intercostal nerves: in type
I, the RCs connected the ganglion to the corresponding intercostal nerve, and in
types II and III, respectively, they connected it to the nerve one level above or
below the corresponding intercostal nerve. Some RCs of types I and II could not
be observed without additional preliminary surgical procedures. Diverse
combinations of RC types arose from the first to the fifth thoracic sympathetic
ganglia, combinations of types I and III being the most common (70%) in the first
sympathetic ganglion and those comprising only type I being most frequent in the
other ganglia. The RCs could not be identified by the naked eye in either fresh
or fixed cadavers, so they were confirmed on the basis of their histological
appearance. These results are expected to improve knowledge of morphological
variations of the RCs in the upper five thoracic sympathetic ganglia, and to
provide helpful information for clinical management in this region. Clin. Anat.,
2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29938831
TI - Beyond hands-on and hands-off: supervisory approaches and entrustment on the
inpatient ward.
AB - CONTEXT: The concept of entrustment has garnered significant attention in medical
specialties, despite variability in supervision styles and entrustment decisions.
There is a need to further study the enactment of supervision on inpatient wards
to inform competency-based assessment design. METHODS: Attending physicians,
while supervising on clinical teaching inpatient wards, were invited to describe
a recent moment of enacting supervision with an internal medicine resident.
Constructivist grounded theory guided data collection and analysis. Interview
transcripts were analysed in iterative cycles to inform data collection. Constant
comparison was used to build a theory of supervision from the identified themes.
RESULTS: In 2016-2017, 23 supervisors from two Canadian universities with
supervision reputations ranging from very involved to less involved participated
in one or two interviews (total: 28). Supervisors were not easily dichotomised
into styles based on behaviour because all used similar oversight strategies.
Supervisors described adjusting between 'hands-on' (e.g. detail oriented) and
'hands-off' (e.g. less visible on ward) styles depending on the context. All also
contended with the competing roles of clinical teacher and care provider.
Supervisors made a distinction between the terms 'entrust' and 'trust', and did
not grant complete entrustment to senior residents. CONCLUSIONS: We propose that
a supervisor's perceived responsibility for the ward underlies adjustments
between 'hands-on' (i.e. personal ward responsibility) and 'hands-off' (i.e.
shared ward responsibility) styles. Our approaches to clinical supervision model
combines this responsibility tension with the tension between patient care and
teaching to illustrate four supervisory approaches, each with unique priorities
influencing entrustment. Given the fluidity in supervision, documenting changes
in oversight strategies, rather than absolute levels of entrustment, may be more
informative for assessment purposes. Research is needed to determine if there is
sufficient association between the supervision provided, the entrustment decision
made and the supervisor's trust in a trainee to use these as proxies in assessing
a trainee's competence.
PMID- 29938832
TI - Assessment of Bayesian expected power via Bayesian bootstrap.
AB - The Bayesian expected power (BEP) has become increasingly popular in assessing
the probability of success for a future trial. While the traditional power
assumes a single value for the unknown effect size Delta and is thus highly
dependent on the assumed value, the BEP embraces the uncertainty around Delta
given the prior information and is therefore a less subjective measure for the
probability of success than the traditional power especially when the prior
information is not rich. Current methods for assessing BEP are often based in a
parametric framework by imposing a model on the pilot data to derive and sample
from the posterior distributions of Delta. The model-based approach can be
analytically challenging and computationally costly especially for multivariate
data sets, and it also runs the risk of generating misleading BEP if the model is
misspecified. We propose an approach based on the Bayesian bootstrap (BBS)
technique to simulate future trials in the presence of individual-level pilot
data, based on which the empirical BEP can be calculated. The BBS approach is
model-free with no assumptions about the distribution of the prior data and also
circumvents the analytical and computational complexity associated with obtaining
the posterior distribution of the Delta. Information from multiple pilot studies
is also straightforward to combine. We also propose the double bootstrap
technique, a frequentist counterpart to the BBS, that shares similar properties
and achieves the same goal as the BBS for BEP assessment. Simulation and case
studies are presented to demonstrate the implementation of the BBS technique and
the double bootstrap technique and to compare the BEP results with model-based
approach.
PMID- 29938833
TI - Estimation of exposure-attributable fractions from time series: A simulation
study.
AB - Burden analysis in public health often involves the estimation of exposure
attributable fractions from observed time series. When the entire population is
exposed, the association between the exposure and outcome must be carefully
modelled before the attributable fractions can be estimated. This article derives
asymptotic convergences for the estimation of attributable fractions for commonly
used time series models (ARMAX, Poisson, negative binomial, and Serfling), using
for the most part the delta method. For the Poisson regression, the estimation of
the attributable fraction is achieved by a Monte Carlo algorithm, taking into
account both an estimation and a prediction error. A simulation study compares
these estimations in the case of an epidemic exposure and highlights the
importance of thorough analysis of the data: When the outcome is generated under
an additive model, the additive models are satisfactory, and the multiplicative
models are poor, and vice versa. However, the Serfling model performs poorly in
all cases. Of note, a misspecification in the form or delay of the association
between the exposure and the outcome leads to mediocre estimation of the
attributable fraction. An application to the fraction of French outpatient
antibiotic use attributable to influenza between 2003 and 2010 illustrates the
asymptotic convergences. This study suggests that the Serfling model should be
avoided when estimating attributable fractions while the model of choice should
be selected after careful investigation of the association between the exposure
and outcome.
PMID- 29938834
TI - Clinical applicability of the Saccadic Vector Optokinetic Perimeter in children
with and without visual impairment.
AB - BACKGROUND: Common paediatric perimetry techniques require central fixation and
subjective responses, which may be challenging for young or cognitively impaired
children. The Saccadic Vector Optokinetic Perimeter (SVOP) was designed to
overcome these challenges by using infra-red eye tracking to assess the visual
field. This study assessed the clinical feasibility of SVOP in children without
visual impairment, comparing it to current paediatric techniques, and in children
with visual impairment. METHODS: Participants were recruited into two cohorts:
children without visual impairment (visual acuity >= 6/7.5) and children with
visual impairment (visual acuity <= 6/18). Children without visual impairment
attempted the Goldmann perimeter, confrontation method, and SVOP. Children with
visual impairment attempted SVOP, when clinically indicated, as part of a full
ophthalmic assessment. Visual field results and test length were recorded.
RESULTS: Twenty-three children without visual impairment (4-14 years old)
attempted all three visual field assessments. Full results were recorded for 91
per cent of children with SVOP, 87 per cent with Goldmann, and 100 per cent with
confrontation SVOP was significantly faster than Goldmann (p < 0.001) and
confrontation (p = 0.003). Thirty-five children with visual impairment (3-19
years old) with visual acuity ranging from 6/9.5 to worse than 6/360 (mean of 0.8
+/- 0.4 logMAR) attempted SVOP, with 26 children able to complete SVOP.
DISCUSSION: This is the largest study to date of the clinical applicability of
SVOP in children without visual impairment, as well as assessing the utility of
SVOP in children with visual impairment. Further research is needed to assess the
accuracy of SVOP in a range of paediatric ocular disorders. SVOP may potentially
offer a visual field assessment method for children previously unable to complete
current paediatric perimetry techniques.
PMID- 29938835
TI - Colocalization of Bunina bodies and TDP-43 inclusions in a case of sporadic
amyotrophic lateral sclerosis with Lewy body-like hyaline inclusions.
AB - Sporadic amyotrophic lateral sclerosis (sALS) is characterized pathologically by
loss of upper and lower motor neurons with occurrence of transactivation response
DNA-binding protein 43 kDa (TDP-43)-immunoreactive skein-like and round hyaline
inclusions. Lewy body-like hyaline inclusions (LBHIs) are also found in a small
proportion of sALS cases as well as in individuals with familial ALS with
mutations in the Cu/Zu superoxide dismutase (SOD1) gene. LBHIs in sALS are
immunopositive for TDP-43, but not for SOD1. The occurrence of Bunina bodies
(BBs) is another key pathological feature of sALS. BBs are immunonegative for TDP
43 but immunopositive for cystatin C, transferrin, peripherin and sortilin
related receptor CNS expressed 2 (SorCS2). Despite differences between BBs and
TDP-43 inclusions in terms of protein constituents and ultrastructure, the two
inclusions are known to be linked. We recently encountered a case of sALS of 10
months duration in which many round hyaline inclusions, LBHIs and BBs were found
in the anterior horn cells of the spinal cord. Our immunohistochemical and
ultrastructural examinations revealed the presence of BBs within the skein-like
and round hyaline inclusions, and in the LBHIs. Colocalization of BB-related
proteins (cystatin C, transferrin and SorCS2) and TDP-43 was also confirmed in
the halo of LBHIs as well as in the marginal portion of the skein-like and round
hyaline inclusions. These findings suggest that there is some relationship
between BBs and TDP-43-immunoreactive inclusions in terms of their formation
processes.
PMID- 29938836
TI - The human IL-17A/F heterodimer regulates psoriasis-associated genes through
IkappaBzeta.
AB - Antagonists of IL-17A and its receptor have proven to be highly effective in the
treatment of psoriasis. However, many of the underlying molecular mechanisms
involved in the pathogenesis of psoriasis are still to be determined. IkappaBzeta
(encoded by the NFKBIZ gene) plays a key role in the development of psoriasis by
mediating IL-17A- and IL-17F-driven effects. Both IL-17A and IL-17F expression
are increased in lesional psoriatic skin. IL-17A/A and IL-17F/F homodimers as
well as the IL-17A/F heterodimer signal through the same receptors. The aim of
this study was to characterize the role of the IL-17A/F heterodimer in the
regulation of NFKBIZ expression and in the regulation of selected psoriasis
associated genes. We demonstrated that IL-17A/F stimulation of human
keratinocytes significantly induced NFKBIZ expression. Moreover, silencing
IkappaBzeta by siRNA revealed that IkappaBzeta is a key regulator of IL-17A/F
inducible psoriasis-associated genes, including CCL20, DEFB4, IL-8, CHI3L1 and
S100A7. In addition, IL-17A/F-induced NFKBIZ expression was mediated by a
mechanism involving the p38 MAPK and NF-kappaB signalling pathways. In
conclusion, we present IkappaBzeta as a novel key regulator of IL-17A/F-driven
effects in psoriasis. Thus, antagonists to IL-17A/F or IkappaBzeta may present a
targeted approach for treating psoriasis.
PMID- 29938837
TI - Preservation of common carp germ cells under hypothermic conditions: Whole tissue
vs isolated cells.
AB - The aim of this study was to optimize the conditions for hypothermic storage of
spermatogonial stem cells (SSCs) and oogonial stem cells (OSCs) of common carp
Cyprinus carpio. This was conducted by storing gonadal tissue or isolated cells
for 24 hr under hypothermic conditions in the first experiment and by testing two
different storage media (L-15 or DMEM supplemented with 10% FBS and 25 mM HEPES)
and regular medium change (every 4 days) during two weeks of hypothermic storage
in the second experiment. During the first 24 hr, isolated cells showed no
decrease in viability, while cells obtained from hypothermically stored tissues
displayed significantly lower viability after only 6 hr (Tukey's HSD, p < 0.01)
indicating that hypothermic storage of isolated cells is superior to storing
tissue pieces. The 2-week trial demonstrated that storage media have a profound
influence, while regular medium exchange does not have a positive effect on cell
viability. Viability of SSCs and OSCs after two weeks was approximately 40% and
25%, respectively; however, survival of ~70% was obtained after 10 days of
storage for SSCs and 7 days for OSCs. Hypothermic storage developed in this study
has many practical applications during the development of surrogate broodstock
technologies for common carp, but also in carp hatcheries and for the
conservation of genetic resources of closely related cyprinid species.
PMID- 29938838
TI - Evaluation of a new T2 Magnetic Resonance assay for rapid detection of emergent
fungal pathogen Candida auris on clinical skin swab samples.
AB - Candida auris is a multidrug-resistant pathogenic yeast whose recent emergence is
of increasing public-health concern. C. auris can colonise multiple body sites,
including patients' skin, and survive for weeks in the health care environment,
facilitating patient-to-patient transmission and fueling health care-associated
outbreaks. Rapid and accurate detection of C. auris colonisation is essential for
timely implementation of infection control measures and to prevent transmission.
Currently, axilla/groin composite swabs, used to assess colonisation status, are
processed using a culture-based method that is sensitive and specific but
requires 14 days. This delay limits the opportunity to respond and highlights the
need for a faster alternative. The culture-independent T2 Magnetic Resonance
(T2MR) system is a rapid diagnostic platform shown to detect target pathogens of
interest from unprocessed blood samples in <5 hours. In this study, a new C.
auris-specific T2 assay was evaluated for screening of the skin surveillance
samples. Inclusivity and limit of detection of the T2 C. auris assay were
assessed with spiked samples in a representative skin flora background. The T2 C.
auris assay recognised isolates from each of the 4 known clades of C. auris and
consistently detected cells at 5 CFU/mL. Finally, 89 clinical axilla/groin swab
samples were processed with the T2 C. auris assay. The culture-based diagnostic
assay was used as a gold standard to determine performance statistics including
sensitivity (0.89) and specificity (0.98). Overall, the T2 C. auris assay
performed well as a rapid diagnostic and could help expedite the detection of C.
auris in patient skin swabs.
PMID- 29938839
TI - Fabrication of Millimeter-Scale, Single-Crystal One-Third-Hydrogenated Graphene
with Anisotropic Electronic Properties.
AB - Periodically hydrogenated graphene is predicted to form new kinds of crystalline
2D materials such as graphane, graphone, and 2D Cx Hy , which exhibit unique
electronic properties. Controlled synthesis of periodically hydrogenated graphene
is needed for fundamental research and possible electronic applications. Only
small patches of such materials have been grown so far, while the experimental
fabrication of large-scale, periodically hydrogenated graphene has remained
challenging. In the present work, large-scale, periodically hydrogenated graphene
is fabricated on Ru(0001). The as-fabricated hydrogenated graphene is highly
ordered, with a ?3 * ?3/R30 degrees period relative to the pristine graphene. As
the ratio of hydrogen and carbon is 1:3, the periodically hydrogenated graphene
is named "one-third-hydrogenated graphene" (OTHG). The area of OTHG is up to 16
mm2 . Density functional theory calculations demonstrate that the OTHG has two
deformed Dirac cones along one high-symmetry direction and a finite energy gap
along the other directions at the Fermi energy, indicating strong anisotropic
electrical properties. An efficient method is thus provided to produce large
scale crystalline functionalized graphene with specially desired properties.
PMID- 29938840
TI - Zero Linear Compressibility in Nondense Borates with a "Lu-Ban Stool"-Like
Structure.
AB - Discovering materials that exhibit zero linear compressibility (ZLC) behavior
under hydrostatic pressure is extremely difficult. To date, only a handful of ZLC
materials have been found, and almost all of them are ultrahard materials with
densified structures. Here, to explore ZLC in nondense materials, a structural
model analogous to the structure of the "Lu-Ban stool," a product of traditional
Chinese woodworking invented 2500 years ago, is proposed. The application of this
model to borates leads to the discovery of ZLC in AEB2 O4 (AE = Ca and Sr) with
the unique "Lu-Ban stool"-like structure, which can obtain a subtle mechanical
balance between pressure-induced expansion and contraction effects. Coupled with
the very wide ultraviolet transparent windows, the ZLC behavior of AEB2 O4 may
result in some unique but important applications. The applications of the "Lu-Ban
stool" model open a new route for pursuing ZLC materials in nondense structural
systems.
PMID- 29938841
TI - Polyclonal antibodies to Paracoccidioides brasiliensis are able to recognise
antigens from different strains from Paracoccidioides species complex, including
Paracoccidioides lutzii LDR2.
AB - Since the new species Paracoccidioides lutzii emerged in 2009, much has been
researched on strains previously considered atypical. Still, there is no
consensus about recognition of antigens from P. lutzii by antibodies directed to
other Paracoccidioides species, which can have great impact on
Paracoccidioidomycosis (PCM) diagnosis. Current research investigated soluble
protein/carbohydrate epitopes from P. lutzii LDR2, Paracoccidioides restrepiensis
B339 and Paracoccidioides americana LDR3 recognised by IgG directed to
Paracoccidioides brasiliensis. Cell free antigens (CFA) were analysed by:
(a)silver and periodic acid-Schiff staining of SDS-PAGE; (b)immunoblot (IB) with
rabbit IgG anti-P. brasiliensis Pb18; (c)IB and ELISA with a pool of PCM
patients' sera before and after treatment with sodium metaperiodate (SMP) to
oxidise carbohydrate epitopes. Both rabbit and human immune sera recognised
several antigens of P. lutzii LDR2, P. restrepiensis B339 and P. americana LDR3.
P. lutzii's gp43 was not observed in IB or silver/PAS staining. SMP treatment
affected reactions with all 3 CFAs, but more intensely with antigens from P.
lutzii LDR2. In conclusion, antibodies directed to P. brasiliensis recognised
antigens from P. lutzii LDR2. The use of any of the recognised antigens in a
broad spectrum diagnostic model for Paracoccidioides species complex needs to be
further investigated.
PMID- 29938842
TI - Cryptic Aspergillus from clinical samples in the USA and description of a new
species in section Flavipedes.
AB - BACKGROUND: In the last few decades there has been an emergence of cryptic
Aspergillus as agents of human infections due to the increase in
immunocompromised population and to the improvement of identification tools.
METHODS: Continuing our study on Aspergillus isolates from clinical origin
deposited in a mycological reference centre in the United States, we selected 37
isolates belonging to less common sections of the genus, to study their species
diversity and detect cryptic species by using a polyphasic approach. RESULTS:
From this set of isolates, a total of 16 species were identified; the most
frequent being A. calidoustus (48.6%, section Usti), A. terreus (13.5%, section
Terrei), and A. nidulans (5.7%, section Nidulantes). The remaining isolates
corresponded to 13 species of rare or cryptic Aspergillus, i.e. A. europaeus
(section Cremei); A. iizukae, A. micronesiensis, A. spelaeus (section
Flavipedes); A. pachycristatus, A. quadrilineatus, A. spinulosporus, A. unguis
(section Nidulantes); A. alabamensis, A. carneus, A. hortai (section Terrei), A.
granulosus (section Usti); and the new species A. suttoniae (section Flavipedes),
which is described here. CONCLUSIONS: Correct identification of cryptic species
is crucial to reveal new potential pathogens, to gather accurate epidemiological
data and to choose an appropriate treatment.
PMID- 29938844
TI - Comparing the values of progesterone in the blood of bitches as measured with a
chemiluminescence immunoassay and a radioimmunoassay.
AB - A 125 I radioimmunoassay (RIA) has long been used to determine the value of
progesterone in serum or plasma of bitches but was discontinued in 2014. A
chemiluminescence immunoassay (CLIA) gained prominence since 2003 to determine
the value of progesterone in serum of bitches but the assay changed in 2012. This
study assessed the agreement between progesterone values obtained with RIA in
plasma (progRIA) and with the post-2012 CLIA (progCLIA) in the serum of bitches.
ProgCLIA was determined in 110 serum samples from 40 bitches in pro-oestrus or
early oestrus and compared to progRIA in plasma samples collected from the same
bitches at the same time, where progRIA had a uniform distribution between 0.5
and 25 nmol/L. Two replicate analyses of each serum or plasma sample were
simultaneously done in the same assay. For RIA and CLIA, the intra-assay CVs were
5.85% and 6.70% and the interassay CVs 8.45% and 9.16%. For RIA and CLIA the
progesterone values obtained with replicate analyses differed by as much as 11%
31% in 25% of samples. On average, the value of progCLIA was 85% of that of
progRIA (95% CI 58%-112%, n = 110), with 88% of progCLIAs being lower than the
progRIAs. This study shows that RIA and CLIA may yield replicate values that
differ by as much as 11%-30% in about a quarter of samples analysed,
necessitating replicate analyses if precise values are required. The study
provides an equation by which to estimate progCLIA from progRIA.
PMID- 29938843
TI - Ion-Migration Inhibition by the Cation-pi Interaction in Perovskite Materials for
Efficient and Stable Perovskite Solar Cells.
AB - Migration of ions can lead to photoinduced phase separation, degradation, and
current-voltage hysteresis in perovskite solar cells (PSCs), and has become a
serious drawback for the organic-inorganic hybrid perovskite materials (OIPs).
Here, the inhibition of ion migration is realized by the supramolecular cation-pi
interaction between aromatic rubrene and organic cations in OIPs. The energy of
the cation-pi interaction between rubrene and perovskite is found to be as strong
as 1.5 eV, which is enough to immobilize the organic cations in OIPs; this will
thus will lead to the obvious reduction of defects in perovskite films and
outstanding stability in devices. By employing the cation-immobilized OIPs to
fabricate perovskite solar cells (PSCs), a champion efficiency of 20.86% and
certified efficiency of 20.80% with negligible hysteresis are acquired. In
addition, the long-term stability of cation-immobilized PSCs is improved
definitely (98% of the initial efficiency after 720 h operation), which is
assigned to the inhibition of ionic diffusions in cation-immobilized OIPs. This
cation-pi interaction between cations and the supramolecular pi system enhances
the stability and the performance of PSCs efficiently and would be a potential
universal approach to get the more stable perovskite devices.
PMID- 29938845
TI - Combinatorial Synthesis of Macromolecular Arrays by Microchannel Cantilever
Spotting (uCS).
AB - Surface-bound microarrays of multiple oligo- and macromolecules (e.g., peptides,
DNA) offer versatile options in biomedical applications like drug screening, DNA
analysis, or medical diagnostics. Combinatorial syntheses of these molecules in
situ can save significant resources in regard to processing time and material
use. Furthermore, high feature densities are needed to enable high-throughput and
low sample volumes as generally regarded in combinatorial chemistry. Here, a
scanning-probe-lithography-based approach for the combinatorial in situ synthesis
of macromolecules is presented in microarray format. Feature sizes below 40 um
allow for the creation of high-density arrays with feature densities of 62 500
features per cm2 . To demonstrate feasibility of this approach for biomedical
applications, a multiplexed array of functional protein tags (HA- and FLAG-tag)
is synthesized, and selective binding of respective epitope recognizing
antibodies is shown. This approach uses only small amounts of base chemicals for
synthesis and can be further parallelized, therefore, opening up a route to
flexible, highly dense, and cost-effective microarrays.
PMID- 29938846
TI - Developmental competence of in vitro matured ovine oocytes vitrified in solutions
with different concentrations of trehalose.
AB - This study aimed to determine the optimum concentration of trehalose in solutions
used for vitrification of in vitro matured (IVM) ovine oocytes. IVM oocytes were
randomly divided into four experimental (vitrified) and one control (fresh)
groups. Experimental groups were treated with different concentrations (0.0,
0.25, 0.5 and 1.0 M) of trehalose. After warming, some viable oocytes were
exposed to 0.25% pronase to test zona pellucida hardening, whereas the others
were fertilized and cultured in vitro for 8 days to evaluate their developmental
competence. Blastocysts quality was assessed by differential staining and TUNEL
test. Survival and developmental rates of oocytes vitrified in the presence of
0.5 M trehalose were significantly higher than those of the other vitrified
groups. Furthermore, there was a significant difference between fresh and
vitrified groups in total blastocyst rate. Analysis of blastocysts quality also
revealed a significant difference between the group treated with 0.5 M trehalose
and other groups in terms of apoptotic index. Furthermore,zona pellucida
digestion time period was longer in trehalose-free (0.0 M) group compared to
other groups. In conclusion, we found that IVM ovine oocytes vitrified in
solutions containing 0.5 M trehalose are fertilization-competent and are able to
produce good-quality blastocysts with an apoptotic index comparable to that of
the fresh oocytes. Therefore, 0.5 M may be considered the optimum concentration
of trehalose to be used in solutions prepared for vitrification of oocytes.
PMID- 29938847
TI - Organic Photovoltaics over Three Decades.
AB - The development of organic semiconductors for photovoltaic devices, over the last
three decades, has led to unexpected performance for an alternative choice of
materials to convert sunlight to electricity. New materials and developed
concepts have improved the photovoltage in organic photovoltaic devices, where
records are now found above 13% power conversion efficiency in sunlight. The
author has stayed with the topic of organic materials for energy conversion and
energy storage during these three decades, and makes use of the Hall of Fame now
built by Advanced Materials, to present his view of the path travelled over this
time, including motivations, personalities, and ambitions.
PMID- 29938848
TI - Effect of parental origin on early life history traits of European eel.
AB - Establishment of European eel (Anguilla anguilla) hatchery production will rely
on selectively bred individuals that produce progeny with the best traits in
successive generations. As such, this study used a quantitative genetic breeding
design, between four females and nine males (four wild-caught and five cultured),
to investigate the effect of paternal origin (wild-caught vs. cultured) and
quantify the relative importance of parental effects, including genetic
compatibility, on early life history (ELH) performance traits (i.e. fertilization
success, embryonic survival at 32 hr post-fertilization, hatch success and larval
deformities at 2 days post-hatch) of European eel. Wild-caught males had higher
(56%) spermatocrit values than cultured males (45%), while fertilization success,
embryonic survival, hatch success and larval deformities were not significantly
impacted by paternal origin. This demonstrates that short-term domestication of
male eels does not negatively affect offspring quality and enables the
consideration of cultured male broodstock in future breeding programmes.
Moreover, paternity significantly explained 9.5% of the variability in embryonic
survival, providing further evidence that paternal effects need to be taken into
consideration in assisted reproduction protocols. Furthermore, maternity
significantly explained 54.8% of the variation for fertilization success, 61.7%
for embryonic survival, 88.1% for hatching success and 62.8% for larval
deformities, validating that maternity is a major factor influencing these
"critical" ELH traits. At last, the parental interaction explained 12.8% of the
variation for fertilization success, 8.3% for embryonic survival, 4.5% for hatch
success and 20.5% for larval deformities. Thus, we conclude that eggs of one
female can develop more successfully when crossed with a compatible male,
highlighting the importance of mate choice for successful propagation of high
quality offspring. Together, this knowledge will improve early offspring
performance, leading to future breeding programmes for this critically endangered
and economically important species.
PMID- 29938849
TI - Validation of body composition using bioelectrical impedance analysis in children
according to the degree of obesity.
AB - This study aimed to validate body composition analysis using bioelectrical
impedance analysis (BIA) against dual-energy X-ray absorptiometry (DXA) in
children with obesity and to compare agreement between BIA and DXA according to
their degree of obesity. Three hundred and sixteen children aged 6-17 years
participated in the Intervention for Childhood and Adolescents Obesity via
Activity and Nutrition study. We divided participants by body mass index (BMI)
percentile (group 1: mild to moderate obesity; group 2: severe obesity) and
compared body composition variables, eg, percentage of body fat (%BF), fat mass
(FM), and fat-free mass (FFM) using BIA and DXA. The %BF and FM of BIA were
significantly lower (-1.8% and -0.8 kg, respectively), and the FFM of BIA was
significantly higher (1.4 kg) than those of DXA. There were significant negative
relationships between the absolute value of differences from BIA and DXA and BMI
z-scores in %BF, FM, and FFM (regression coefficient [beta]: -1.39, 95%
confidence interval [CI]: -1.81 to -0.97; beta: -0.34, 95%CI: -0.61 to -0.06;
beta: -0.73, 95%CI: -1.03 to -0.44, respectively). The gap of body compositions
between BIA and DXA decreased as participants became more obese, and the
differences of FM in boys with severe obesity and the differences of %BF and FFM
in girls with severe obesity were much less than those in children with mild to
moderate obesity. In conclusion, the agreement between DXA and BIA was better for
children with severe obesity than for children with mild to moderate obesity.
PMID- 29938850
TI - Population density and proximity to junior developmental teams affect the
development of National Hockey League draftees.
AB - Inconsistencies in community size effects found between and within countries
(Baker et al Eur J Sport Sci. 2009;9:329-339; Bruner et al J Sports Sci.
2011;29:1337-1344; Wattie et al J Sports Sci. 2018;36:436-444) suggest population
size may not be an accurate predictor of athlete development and that other
proxies of early environmental characteristics are needed. Researchers have begun
to explore the influence of population density and proximity to local sport clubs
on athlete development in European countries; however, similar analysis remains
to be conducted in Canadian ice hockey. The current study focused on National
Hockey League (NHL) draftees and explored whether population density and
proximity to Canadian Hockey League teams were associated with the number of
draftees produced. Linear regression analyses showed a significant positive
relationship between population density and the development of draftees in all
provincial regions; however, a significant negative relationship between
proximity to CHL teams and NHL draftee development was observed in four out of
six provincial regions (British Columbia, Ontario, Quebec, and the Atlantic
Provinces). Moreover, population density appeared to be a better predictor of NHL
talent development than proximity to CHL teams. Future research may benefit from
exploring the effects of these two variables within population size categories,
as well as between different regions within provinces.
PMID- 29938851
TI - Comparison of sample preparation techniques and data analysis for the LC-MS/MS
based identification of proteins in human follicular fluid.
AB - The proteomic analysis of complex body fluids by liquid chromatography tandem
mass spectrometry (LC-MS/MS) analysis requires the selection of suitable sample
preparation techniques and optimal parameter settings in data analysis software
packages to obtain reliable results. Proteomic analysis of follicular fluid, as a
representative of a complex body fluid similar to serum or plasma, is difficult
as it contains a vast amount of high abundant proteins and a variety of proteins
with different concentrations. However, the accessibility of this complex body
fluid for LC-MS/MS analysis is an opportunity to gain insights into the status,
the composition of fertility-relevant proteins including immunological factors or
for the discovery of new diagnostic and prognostic markers for, for example, the
treatment of infertility. In this study, we compared different sample preparation
methods (FASP, eFASP and in-solution digestion) and three different data analysis
software packages (Proteome Discoverer with SEQUEST, Mascot and MaxQuant with
Andromeda) combined with semi- and full-tryptic databank search options to obtain
a maximum coverage of the follicular fluid proteome. We found that the most
comprehensive proteome coverage is achieved by the eFASP sample preparation
method using SDS in the initial denaturing step and the SEQUEST-based semi
tryptic data analysis. In conclusion, we have developed a fractionation-free
methodical workflow for in depth LC-MS/MS-based analysis for the standardized
investigation of human follicle fluid as an important representative of a complex
body fluid. Taken together, we were able to identify a total of 1392 proteins in
follicular fluid.
PMID- 29938852
TI - Diurnal profile of interstitial glucose following dexamethasone prophylaxis for
chemotherapy treatment of gynaecological cancer.
AB - AIMS: Hyperglycaemia, a side-effect of acute glucocorticoid exposure, is
associated with poor outcome in those undergoing chemotherapy. The incidence,
risk factors and diurnal profile of glucocorticoid-induced glucose dysregulation
in the context of chemotherapy treatment remain incompletely understood. METHODS:
Blinded continuous interstitial glucose monitoring was performed on 16 women
without diabetes for 24 h prior to and 5 days following carboplatin/paclitaxel
chemotherapy combined with dexamethasone treatment for gynaecological cancer. At
the end of the treatment period, glucose data were analysed and integrated with
baseline metabolic and anthropomorphic variables. RESULTS: 15/16 (94%) women
exhibited elevated glucose levels (> 11.1 mmol/l). Peak glucose levels were
highest on the day of treatment (median 14.45 mmol/l, range 10.2-22.2 mmol/l) and
total time spent with an elevated interstitial glucose level was highly variable
(median 3.6 h, range 0.0-55.1 h). Peak interstitial glucose levels occurred
predominantly, but not exclusively, in the afternoon (13.00-15.00) and evening
(19.00-22.00); however elevated levels were noted throughout the 24-h period.
Baseline HbA1c was independently associated with severity and duration of
elevated glucose levels in a regression adjusted for baseline BMI. CONCLUSIONS:
These data report for the first time that high glucose levels are encountered by
nearly all women following this regimen, the severity and duration of which are
independently associated with HbA1c . Further work is required to determine if
controlling glucose levels during treatment influences outcome.
PMID- 29938853
TI - Sensitive monitoring of taurine biomarker in unprocessed human plasma samples
using a novel nanocomposite based on poly(aspartic acid) functionalized by
graphene quantum dots.
AB - The rapid and accurate determination of the level of taurine biomarker in various
tissues and body fluids can be of great interest in the early diagnosis of
several important pathologies and diseases. For the first time, this study
reports on the electropolymerization of a low toxic and biocompatible
nanocomposite "poly(aspartic acid)-graphene quantum dots (GQDs)" as a novel
strategy for surface modification of glassy carbon electrode and preparation a
new interface for measurement of taurine. Electrochemical deposition, as a well
controlled synthesis procedure, has been used for subsequently layer-by-layer
preparation of GQDs nanostructures on poly(aspartic acid) using cyclic
voltammetry techniques in the regime of -1.5 to 2 V. The field emission scanning
electron microscopy indicated immobilization of uniformly GQDs onto poly(aspartic
acid) film. The modified electrode appeared as an effective electroactivity for
detection of taurine biomarker using cyclic voltammetry, chronoamperometry, and
differential pulse voltammetry. Enhancement of peak currents is ascribed to the
fast heterogeneous electron transfer kinetics that arise from the synergistic
coupling between the excellent properties of poly(aspartic acid) as
semiconducting polymer, GQDs as high density of edge plane sites, and subtle
electronic characteristics to chemical modification. Under the optimized analysis
conditions, the prepared sensor for detection of taurine showed a low limit of
quantification 0.001mM. Finally, the resulting prepared sensor allow the
quantification of these biomarkers directly in biological samples without need of
derivatization schemes or sample pretreatment.
PMID- 29938854
TI - Designing Metal-Free Frustrated Lewis Pairs Catalyst for the Efficient
Dehydrogenation of Ammonia Borane.
AB - Ammonia borane (AB) has been in the spotlight for the chemical storage of
hydrogen over the past decade. However, the development of methods for efficient
and controlled hydrogen release from AB under mild conditions is still underway.
Herein, using density functional theory (DFT) computations, we designed a metal
free frustrated Lewis pair (FLP) catalyst o-(BPh2 )C6 H4 (NiPr2 ) (M1) that can
efficiently dehydrogenate AB to release more than two equivalents of H2 under
mild conditions. Catalyst M1 can dehydrogenate not only AB to H2 N=BH2 (AOB) and
H2 , but also oligomers of AOB with rather low free-energy barriers. The high
dehydrogenation activity of M1 is the key of new oligomerization routes to the
efficient dehydrogenation of AB to borazine (BZ) or H2 B-(NH=BH)n -NH2 (PIB) and
finally to polyborazylene (PBZ) so that more than two equivalents of H2 can be
released. A first-principle kinetic Monte Carlo (KMC) study reveals that the
activity of our catalytic system can be tuned by varying the initial
concentration of M1 and AB. This work can guide the design of catalyst for the
highly efficient utilization of AB as a hydrogen storage material.
PMID- 29938855
TI - Programmed death-ligand 1 immunoexpression in matched biopsy and liquid-based
cytology samples of advanced stage non-small cell lung carcinomas.
AB - OBJECTIVE: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is
essential in patients of advanced non-small-cell lung cancer to determine
eligibility for immunotherapy. PD-L1 IHC assays have been clinically validated
only on formalin-fixed paraffin-embedded tissue; however, lung cancer is
frequently diagnosed on cytology. PD-L1 immunocytochemistry (ICC) has shown high
concordance of immunoexpression between cytology samples and paired small
biopsies. Feasibility of liquid-based cytology (LBC) smears for PD-L1 ICC has not
been analysed previously. METHODS: PD-L1 ICC and IHC (clone SP263) were performed
on paired LBC smears and small biopsies, respectively, in patients with advanced
non-small-cell lung cancer. Cases with fewer than 100 viable tumour cells on LBC
smear/biopsy were excluded from analysis. PD-L1 was interpreted positive when 25%
or more tumour cells showed membranous and/or cytoplasmic protein expression of
any intensity greater than background staining. RESULTS: A total of 26 patients,
harbouring adenocarcinomas (50%) and squamous cell carcinomas (50%), had
available bronchial brushings/washings processed as LBC smears and concurrently
obtained endobronchial biopsies. PD-L1 IHC was interpreted positive in 46%
(12/26) biopsies. PD-L1 ICC was interpreted positive in 35% (9/26) LBC smears,
all of which were IHC-positive. No IHC-negative case was positive on cytology.
The overall concordance between LBC smears and small biopsies was 88.4%.
CONCLUSION: PD-L1 ICC can be performed on LBC processed smears, with certain
challenges in interpretation inherent to LBC smears and their processing methods.
Nevertheless, they represent a potential resource for ICC, especially when
alternate histology material is not available. Future studies are required to
validate the predictive value of PD-L1 ICC on LBC smears.
PMID- 29938857
TI - Assessments of tumor metabolism with CEST MRI.
AB - Chemical exchange saturation transfer (CEST) is a relatively new contrast
mechanism for MRI. CEST MRI exploits a specific MR frequency (chemical shift) of
a molecule while generating an image with good spatial resolution using standard
MRI techniques, combining the specificity of MRS with the spatial resolution of
MRI. Many CEST MRI acquisition methods have been developed to improve analyses of
tumor metabolism. GluCEST, CrCEST, and LATEST can map glutamate, creatine, and
lactate, which are important metabolites involved in tumor metabolism. GlucoCEST
MRI tracks the pharmacokinetics of glucose transport and cell internalization
within tumors. CatalyCEST MRI detects enzyme catalysis that changes a substrate
CEST agent. AcidoCEST MRI measures extracellular pH of the tumor microenvironment
by exploiting a ratio of two pH-dependent CEST signals. This review describes
each technique, the technical issues involved with CEST MRI and each specific
technique, and the merits and challenges associated with applying each CEST MRI
technique to study tumor metabolism.
PMID- 29938856
TI - Activity of preparations from Spilanthes oleracea, propolis, Nigella sativa, and
black garlic on different microorganisms involved in oral diseases and on total
human salivary bacteria: A pilot study.
AB - Due to continuous rise in antibiotic resistance, there is a need for alternative
treatment options to reduce the levels of oral pathogens for the maintenance of
oral as well as overall health. The aim of this study was to evaluate the in
vitro antibacterial potential of tinctures of Spilanthes oleracea and propolis,
Nigella seed oil, and an ethanolic extract of black garlic on microorganisms
involved in oral diseases. Both the minimum inhibitory concentration assay and
the minimum bactericidal/fungicidal concentration assay were used in this study.
Inhibition effects against total human salivary bacteria were also determined.
Our results show that all of the preparations tested had potent antimicrobial
activities. When measured 10 min after exposure, even low concentrations of the
propolis tincture were found to have killed more than 99% of salivary bacteria,
whereas Spilanthes tincture and black garlic extract killed more than 90% and
Nigella seed oil more than 60% of the pathogens. This suggests that all
preparations are promising candidates for the use in oral health care products
and that all have the potential to control biofilm associated infections.
PMID- 29938859
TI - The Peer Relationships of Those Who Have Experienced Adoption or Foster Care: A
Meta-Analysis.
AB - This meta-analytic review examines the presence and quality of close peer
relationships for adoptees and individuals with foster care experience. Results
indicate that adoptees show difficulty forming close peer relationships compared
with biologically reared individuals, but they do not differ in the quality of
these relationships. In contrast, those with foster care experience report lower
quality peer relationships than biologically reared individuals. Additionally,
this meta-analysis includes prevalence rates of close peer relationships that
illustrate most adoptees and foster youth report having high-quality peer
relationships. These findings have important implications for intervention and
prevention efforts and offer directions for future research on peer relationships
among adoptees and foster youth, but should be considered in light of the
presence of some publication bias.
PMID- 29938858
TI - Runx1 Role in Epithelial and Cancer Cell Proliferation Implicates Lipid
Metabolism and Scd1 and Soat1 Activity.
AB - The role of lipid metabolism in epithelial stem cell (SC) function and
carcinogenesis is poorly understood. The transcription factor Runx1 is known to
regulate proliferation in mouse epithelial hair follicle (HF) SCs in vivo and in
several mouse and human epithelial cancers. We found a novel subset of in vivo
Runx1 HFSC target genes related to lipid metabolism and demonstrated changes in
distinct classes of lipids driven by Runx1. Inhibition of lipid-enzymes Scd1 and
Soat1 activity synergistically reduces proliferation of mouse skin epithelial
cells and of human skin and oral squamous cell carcinoma cultured lines. Varying
Runx1 levels induces changes in skin monounsaturated fatty acids (e.g., oleate, a
product of Scd1) as shown by our lipidome analysis. Furthermore, varying Runx1
levels, the inhibition of Scd1, or the addition of Scd1-product oleate,
individually affects the plasma membrane organization (or fluidity) in mouse
keratinocytes. These factors also affect the strength of signal transduction
through the membranes for Wnt, a pathway that promotes epithelial (cancer) cell
proliferation and HFSC activation. Our working model is that HFSC factor Runx1
modulates the fatty acid production, which affects membrane organization,
facilitating signal transduction for rapid proliferation of normal and cancer
epithelial cells. Stem Cells 2018;36:1603-1616.
PMID- 29938860
TI - A transatlantic cooperation for enriched neuroscience training.
PMID- 29938861
TI - The enigma of a pulmonary papillary lesion.
PMID- 29938862
TI - Use of radiography, ultrasonography, and computed tomography in the diagnosis of
a pyogranulomatous ureteral mass in a cat.
AB - An 8-year-old, spayed female, domestic short haired cat, with diabetes mellitus,
was presented to the University of Florida Veterinary Medical Center for an acute
onset of vomiting and inappetence. Abdominal radiographs showed mild
retroperitoneal effusion and asymmetric left-sided renomegaly. Subsequently, on
abdominal ultrasound, a hypoechoic left ureteral mass with left hydronephrosis
and hydroureter was identified. An abdominal computed tomography revealed a
heterogeneously contrast-enhancing mass circumferentially surrounding the mid to
distal left ureter, mild retroperitoneal effusion, left-sided hydronephrosis and
hydroureter, and a distally located ureteral calculus at the level of the
ureterovesicular junction. The patient was diagnosed with left-sided
pyogranulomatous ureteritis via surgical biopsy and histopathology.
PMID- 29938863
TI - Effect of migration and environmental heterogeneity on the maintenance of
quantitative genetic variation: a simulation study.
AB - The paradox of high genetic variation observed in traits under stabilizing
selection is a long-standing problem in evolutionary theory, as mutation rates
appear too low to explain observed levels of standing genetic variation under
classic models of mutation-selection balance. Spatially or temporally
heterogeneous environments can maintain more standing genetic variation within
populations than homogeneous environments, but it is unclear whether such
conditions can resolve the above discrepancy between theory and observation.
Here, we use individual-based simulations to explore the effect of various types
of environmental heterogeneity on the maintenance of genetic variation (VA ) for
a quantitative trait under stabilizing selection. We find that VA is maximized at
intermediate migration rates in spatially heterogeneous environments and that the
observed patterns are robust to changes in population size. Spatial environmental
heterogeneity increased variation by as much as 10-fold over mutation-selection
balance alone, whereas pure temporal environmental heterogeneity increased
variance by only 45% at max. Our results show that some combinations of spatial
heterogeneity and migration can maintain considerably more variation than
mutation-selection balance, potentially reconciling the discrepancy between
theoretical predictions and empirical observations. However, given the narrow
regions of parameter space required for this effect, this is unlikely to provide
a general explanation for the maintenance of variation. Nonetheless, our results
suggest that habitat fragmentation may affect the maintenance of VA and thereby
reduce the adaptive capacity of populations.
PMID- 29938865
TI - Diminished circulating concentration of interleukin-35 in Helicobacter pylori
infected patients with peptic ulcer: Its association with FOXP3 gene
polymorphism, bacterial virulence factor CagA, and gender of patients.
AB - BACKGROUND: IL-35 modulates immune and inflammatory responses during infections.
Here, we investigated IL-35 levels and a single nucleotide polymorphism,
rs3761548, in FOXP3 gene in Helicobacter pylori-infected patients with peptic
ulcer (PU), to clarify possible associations. MATERIALS AND METHODS: This study
includes 100 H. pylori-infected PU patients, 100 H. pylori-infected asymptomatic
subjects (AS), and 100 noninfected healthy subjects (NHSs). Serum IL-35 levels
and the genotyping were determined using ELISA and RFLP-PCR methods,
respectively. RESULTS: In PU patients, the IL-35 levels were lower than AS and
NHS groups (P < .001). The IL-35 levels in CagA+ H. pylori-infected participants
from PU and AS groups were lower than individuals infected with CagA- strains (P
< .02 and P < .04, respectively). Women had higher IL-35 levels than men among
PU, AS, and NHS groups (P < .0001). In PU patients, AA genotype and A allele at
rs3761548 were more frequent than total healthy subjects (AS + NHS groups) and
associated with an increased PU risk (AA genotype: OR = 5.51, P < .0001; A
allele: OR = 3.857, P < .002). In PU and AS groups, IL-35 levels were lower in
subjects displaying AA genotype or A allele than subjects displaying CC genotype
or C allele, respectively (P < .0001 and P < .03 for PU patients; P < .001 and P
< .02 for AS group, respectively). CONCLUSIONS: Decreased IL-35 levels could be
involved in PU development in H. pylori-infected individuals. IL-35 levels are
affected by CagA status of H. pylori, participants gender, and genetic variations
at rs3761548. The AA genotype and A allele at rs3761548 could represent a risk
factor for PU development.
PMID- 29938866
TI - Association of QRS-T angle and heart rate variability with major cardiac events
and mortality in hemodialysis patients.
AB - INTRODUCTION: Mortality in hemodialysis (HD) patients is high with significant
proportion attributed to fatal arrhythmias. In a pilot study, we showed that
intradialytic electrocardiographic (ECG) monitoring can yield stable profiles of
selected repolarisation descriptors and heart rate variability (HRV) parameters.
This study investigated the relationship of these ECG markers with major adverse
cardiac events (MACE) and mortality. METHODS: Continuous ECGs were obtained
during HD and repeated five times at 2-week intervals. The QRS-T angle calculated
as Total Cosine R to T (TCRT) and T-wave morphology dispersion (TMD) were
calculated in overlapping 10 s ECG segments. High- (HF) and low (LF)-frequency
components and the LF/HF ratio of HRV were calculated every 5 min. These indices
were averaged during the first hour of dialysis and subsequently overall
recordings in each subject. RESULTS: All ECG parameters were available in 72
patients aged 61 +/- 15, 23 (31.9%) females and 26 (36.1%) diabetics. After a
median follow up of 54.8 months, 16 patients died, 20 were transplanted, and 9
suffered MACE. TCRT (in degrees) was higher and LF/HF was lower in patients who
died compared to survivors (112 +/- 30 vs. 73 +/- 35, p = 0.000 and 0.222 +/-
0.418 vs. 0.401 +/- 0.274, p = 0.000, respectively) and in MACE positive compared
to negative (117 +/- 40 vs. 77 +/- 34, p = 0.017 and 0.125 +/- 0.333 vs.0.401 +/-
0.274, p = 0.007 respectively). In multivariate Cox regression analysis of
mortality risk adjusted for age, diabetes mellitus, and coronary artery disease,
TCRT and LF/HF remained significant predictors (p < 0.05). CONCLUSION: QRS-T
angle and HRV may serve risk assessment in future prospective studies in HD
patients.
PMID- 29938864
TI - Helicobacter pylori infection reduces the risk of Barrett's esophagus: A meta
analysis and systematic review.
AB - INTRODUCTION: The prevalence of Helicobacter pylori infection (HPI) has been
decreasing in developed countries, with an increasing prevalence of Barrett's
esophagus (BE) and esophageal adenocarcinoma (EAC) at the same time. The aim of
our meta-analysis was to quantify the risk of BE in the context of HPI. METHODS:
A systematic search was conducted in 3 databases for studies on BE with data on
prevalence of HPI from inception until December 2016. Odds ratios for BE in HPI
were calculated by the random effects model with subgroup analyses for
geographical location, presence of dysplasia in BE, and length of the BE segment.
RESULTS: Seventy-two studies were included in the meta-analysis, including 84 717
BE cases and 390 749 controls. The overall analysis showed that HPI reduces the
risk of BE; OR = 0.68 (95% CI: 0.58-0.79, P < .001). Subgroup analyses revealed
risk reduction in Asia OR = 0.53 (95% CI: 0.33-0.84, P = .007), Australia OR =
0.56 (95% CI: 0.39-0.80, P = .002), Europe OR = 0.77 (95% CI: 0.60-0.98, P =
.035), and North-America OR = 0.59 (95% CI: 0.47-0.74, P < .001). The risk was
significantly reduced for dysplastic BE, OR = 0.37 (95% CI: 0.26-0.51, P < .001)
for non-dysplastic BE, OR = 0.51 (95% CI: 0.35-0.75, P = .001), and for long
segment BE, OR = 0.25 (95% CI: 0.11-0.59, P = .001) in case of HPI. CONCLUSIONS:
This extensive meta-analysis provides additional evidence that HPI is associated
with reduced risk of BE. Subgroup analyses confirmed that this risk reduction is
independent of geographical location. HPI is associated with significantly lower
risk of dysplastic, non-dysplastic, and long segment BE.
PMID- 29938867
TI - Neurotensin, substance P, and insulin enhance cell migration.
AB - Neurotensin, substance P, and insulin have been demonstrated to improve wound
healing in vivo. However, the mechanism behind their effect is still not fully
understood. This study investigates the effects leading to enhanced scratch
closure by these peptides in vitro. The skin keratinocyte cell line, HaCaT, was
used to test scratch closure effects of the peptides and alterations of cytokine
levels. HUVEC cells were used to test the angiogenic effect of the peptides.
Furthermore, clinical isolates of Staphylococcus lugdunensis were used to examine
the potential antimicrobial activity of each peptide. Our results demonstrate
that neurotensin, substance P, and insulin had significant migratory effects in
scratch assays were neurotensin had the lowest effect. Furthermore, we
investigated use of the peptides in combination. When substance P was used in
combination with neurotensin, the cell migratory capacity was decreased, and the
peptides showed a negative correlation (r = -0.298, P < .001). Neurotensin and
insulin significantly increased levels of monocyte chemoattractant protein-1 (P <
.001) secreted from white blood cells, whereas substance P showed a tendency.
Interestingly, neurotensin increased the level of monocyte chemoattractant
protein-1 significantly compared to substance P (P < .01). Additionally, the
peptides decreased TNFalpha mRNA levels (P < .001) in HaCaT cells, whereas only
neurotensin and insulin decreased IL-8 mRNA (P < .001) but had no significant
effect on IL-6 mRNA levels. Surprisingly, substance P increased IL-6 mRNA 9-fold
(P < .001). Furthermore, we demonstrate that the peptides increased angiogenesis
in the HUVEC cells (P < .001). Finally, S. lugdunensis isolates were not
susceptible to the peptides. We demonstrate that the peptides worked differently
on HaCaT cells, but substance P acted differently than neurotensin on cytokine
levels expression as well as on migration of HaCaT cells. On the contrary,
neurotensin and insulin worked similarly. All of these aspects are crucial for
proper wound healing, and the results suggest multiple mechanisms for wound
healing properties of these peptides.
PMID- 29938868
TI - The presence of atrial fibrillation in Takotsubo cardiomyopathy is predictive of
mortality: Systematic review and meta-analysis.
AB - INTRODUCTION: Atrial fibrillation (AF) is known as the most common arrhythmia and
an independent risk factor for mortality. Recent studies suggest that AF is
associated with morbidity and mortality in Takotsubo cardiomyopathy (TTC).
However, a systematic review and meta-analysis of the literature have not been
done. We assessed the association between AF in patients with TTC and mortality
by a systematic review of the literature and a meta-analysis. METHODS: We
comprehensively searched the databases of MEDLINE and EMBASE from inception to
January 2018. Included studies were published prospective or retrospective cohort
studies that compared all-cause mortality in TTC with AF versus without AF. Data
from each study were combined using the random-effects, generic inverse variance
method of DerSimonian and Laird to calculate risk ratios and 95% confidence
intervals. RESULTS: Five studies from August 2008 to October 2017 were included
in this meta-analysis involving 2,321 subjects with TTC (243 with AF and 2,078
without AF). The presence of AF was associated with all-cause mortality (pooled
odds ratio = 2.19, 95% confidence interval: 1.57-3.06, p < 0.001, I 2 = 0%).
CONCLUSION: Atrial fibrillation increased all-cause mortality by double among
patients with TTC compared to without it. Our study suggests that the presence of
AF in TTC is prognostic for all-cause mortality.
PMID- 29938869
TI - A New Halophilic Heterolobosean Flagellate, Aurem hypersalina gen. n. et sp. n.,
Closely Related to the Pleurostomum-Tulamoeba Clade: Implications for Adaptive
Radiation of Halophilic Eukaryotes.
AB - Halophilic protozoa are independently scattered across the molecular phylogeny of
eukaryotes; most of which are assigned to Heterolobosea. Here, we isolated a
biflagellate from a hypersaline water of 3420/00 salinity. This isolate shared
several morphological features with typical halophilic heterolobosean
flagellates. In addition, molecular phylogenetic trees of the 18S rRNA gene
sequences clearly indicated flagellate is a heterolobosean species closely
related to the halophilic Tulamoebidae. However, the flagellate was not
accommodated to any described genus. Cells were ovoid-shaped, and no amoebae were
observed. The two unequal flagella beat heterodynamically. An ear-like bulge at
the margin of a cytostomal groove was observed. Flagellates could grow at 100
2000/00 salinity, suggesting an obligately halophilic species. Currently, it
appears that the new halophilic Aurem hypersalina forms a strong clade with
Tulamoebidae, and is sister to the Tulamoebidae, indicating that this new clade
is composed almost entirely of obligate halophilic taxa. Thus, A. hypersalina and
the Tulamoebidae clade currently represent a unique adaptive radiation of
halophilic eukaryotes.
PMID- 29938870
TI - Survival analysis of multiple peptide vaccination for the selection of correlated
peptides in urological cancers.
AB - Peptide-based cancer vaccines are able to induce strong immune responses, but
their clinical results are unsatisfactory. To determine clinically correlated
peptides, we analyzed survival data from urological cancer patients treated by
personalized peptide vaccination (PPV), in which different multiple peptides were
used for individual patients based on human leukocyte antigen (HLA) type and pre
existing immunity. Survival data were obtained from a database of 265 urological
cancer patients treated in 5 clinical PPV trials comprising 154 patients with
castration-resistant prostate cancer (CRPC) and 111 patients with advanced
urothelial cancer (UC). Expression of tumor-associated antigens (TAA) was
evaluated in 10 prostate cancer tissues, 4 metastatic lymph nodes from prostate
cancer, and 10 UC tissues using immunohistochemical staining. Clinical efficacy
of individual peptides for overall survival was evaluated by the Cox proportional
hazards regression model. All TAA coding candidate peptides used in PPV treatment
were expressed in tumor cells from prostate cancer and UC samples except for
p56Lck in both, and prostate-specific antigen (PSA), prostatic acid phosphatase
(PAP) and prostate-specific membrane antigen (PSMA) in the UC samples. Patients
with the following peptides had a significantly longer survival than patients
without the peptides (hazard ratio <1.0, 95% confidence intervals <1.0 and P <
.05): SART3-109, PTHrP-102, HNPRL-140, SART3-302 and Lck-90 in CRPC patients, and
EGF-R-800, Lck-486, PSMA-624, CypB-129 and SART3-734 in advanced UC patients,
respectively. Correlated peptides selected using both survival data and pre
existing immunity for PPV treatment may enhance the clinical benefits for
urological cancer patients.
PMID- 29938871
TI - Alcohol overuse and intracerebral hemorrhage: characteristics and long-term
outcome.
AB - BACKGROUND AND PURPOSE: Alcohol overuse (AOu) is considered an important risk
factor for spontaneous intracerebral hemorrhage (ICH). The clinical and outcome
characteristics of these patients (AOu-ICH) are not well known. METHODS: All
patients with ICH admitted to a single university tertiary stroke center were
prospectively studied from May 2005 to May 2015. Demographic profiles, radiologic
characteristics and clinical outcomes of patients with acute ICH and previous AOu
(>40 g/day or >300 g/week) were analyzed. RESULTS: During the study period, 555
patients with spontaneous primary ICH met the inclusion criteria. A total of 81
patients (14.6%) reported AOu (24.3% of men vs. 3.1% of women; P < 0.0001; mean
age, 63 years old for AOu vs. 74 years old for non-AOu; P < 0.0001). Of the
classic cardiovascular risk factors, only smoking was associated with AOu (63%
vs. 12.2% of non-AOu; P < 0.0001). Initial severity and hematoma volume were
similar in both groups, with no observed differences in stroke care or in
hospital medical complications. Patients with AOu had worse outcome (modified
Rankin Scale score, 3-6 points) than patients without AOu at 3 months [odds ratio
(OR), 2.50; 95% confidence interval (CI), 1.32-4.75; P = 0.005] and 12 months
(OR, 2.47; 95% CI, 1.23-5.00; P = 0.011). A similar trend was observed at 5 years
(OR, 2.48; 95% CI, 0.96-6.39; P = 0.059). CONCLUSIONS: Alcohol overuse was
present in 14.6% of patients with ICH, who were predominantly male, smokers and a
mean of 11 years younger than the non-AOu group. Despite a lack of differences in
initial clinical severity, stroke care and early medical complications, patients
with AOu had worse short- and long-term outcomes.
PMID- 29938872
TI - Immunoexpression of SOX-2 in oral leukoplakia.
AB - OBJECTIVE: This study was conducted to correlate and compare the immunoexpression
of sex-determining region Y-box 2 (SOX-2) in oral leukoplakia (OL) lesions with
that in normal buccal mucosa (control). MATERIALS AND METHODS: In this
observational study, OL with low-risk (n = 34) and high-risk (n = 33) dysplasia
and control samples (n = 25) were subjected to immunohistochemical analysis for
SOX-2. In the epithelium, SOX-2 positive and negative cells, as well as
semiautomatic segmentation of the immunopositive nuclear area were counted.
Statistical tests included chi-square, one-way analysis of variance, Tukey, and
Games-Howell. The level of significance was 5%. RESULTS: Groups with OL lesions
(low and high-risk) showed higher mean numbers of SOX-2 positive cells (63.47 +/-
25.70 and 68.18 +/- 21.17) compared to the control group (45.85 +/- 27.38) (p =
0.00). Groups with OL lesions (low and high-risk) exhibited higher mean positive
nuclear area (0.24 +/- 0.47 and 1.09 +/- 2.06) compared to the control group
(0.00 +/- 0.01) (p = 0.01). CONCLUSION: Oral leukoplakia lesions showed a higher
expression of SOX-2, suggesting its contribution to the pathogenesis of OL.
PMID- 29938873
TI - Status epilepticus due to acute encephalitis: NORSE does not necessarily mean
worse.
PMID- 29938874
TI - Parent-directed commentaries during children's hearing habilitation appointments:
a practice in family-centred care.
AB - BACKGROUND: Family-centred care (FCC) is recognized as best practice in the
delivery of early intervention services for children with hearing loss (HL) and
their families. However, there has been little research involving direct
observation of family-centred communication practices in paediatric hearing
habilitation appointments, which means little is currently known about how family
members are involved within appointments, and how FCC is accomplished by health
professionals through their interactions with families. AIMS: To examine the
interaction between hearing healthcare professionals, children with HL, and their
parents within video-recorded paediatric hearing habilitation appointments
(including both audiology and speech and language therapy appointments), with a
particular focus on how parents were involved in the interaction. METHODS &
PROCEDURES: The data for this study involved a corpus of 48 video-recorded
paediatric hearing habilitation appointments from three clinical sites (including
33 audiology appointments and 15 speech pathology appointments). Participants
included 14 audiologists, 8 speech and language therapists, 41 children with HL
(aged 18 months and over) and 48 of their attending family members (e.g.,
parents/carers). The data were analyzed using conversation analysis. OUTCOMES &
RESULTS: Analysis revealed one specific practice that health professionals used
to engage parents in the interaction during child-directed assessment and therapy
tasks: that of 'parent-directed commentaries', where health professionals shifted
their attention to the parent(s) to describe or evaluate what they were observing
during appointment tasks. Health professionals were observed to produce two types
of parent-directed commentaries: (1) a positive evaluation of the child's just
prior response; and (2) an account for the child's prior behaviour (sometimes
also accompanied by a positive evaluation). These commentaries appeared at
systematic points in the interaction when the child had been displaying
difficulty with their response to the health professional. The parent-directed
commentaries accomplished several important functions: they engaged the parent's
attention in the interaction; focused the parent's attention on positive
responses from the child (while shrouding less positive responses); played down
potential negative perceptions of the child's previous missed/incorrect
responses; and provided parents with reassurance of their child's progress during
the ongoing task. CONCLUSIONS & IMPLICATIONS: The parent-directed commentaries
identified in this study provide an example of the practical, interactional
resources that health professionals can draw on within paediatric appointments to
facilitate FCC with parents.
PMID- 29938875
TI - Association of ADHD with recurrent hypoglycemia in type 1 DM.
AB - OBJECTIVE: Data regarding the association between hypoglycemia and attention
deficit hyperactivity disorder (ADHD) in children and adolescents with type 1
diabetes mellitus (T1DM) are limited. This study investigated whether
hypoglycemia was associated with the risk of ADHD in young people with type 1
diabetes mellitus T1DM. METHODS: Children and adolescents with a diagnosis of
T1DM were identified from the Longitudinal National Health Insurance Database in
Taiwan from 1998-2011. Among them who were newly diagnosed with hypoglycemia
during 2000-2007 were selected for the hypoglycemia cohort. The hypoglycemia
diagnosis date was defined as the index date. Those who were diagnosed with ADHD
before the index date were excluded. The main outcome was the development of
ADHD. In total, 726 participants with hypoglycemia and 2,852 participants without
hypoglycemia were included in this study. RESULTS: The overall incidence density
of ADHD was markedly increased among cohort with hypoglycemia compared with
cohort without hypoglycemia (4.74 vs. 1.65 per 1,000 person-years), with an
adjusted hazard ratio (aHR) of 2.73 (95% confidence interval [CI] = 1.50-4.98).
Cohort with hypoglycemia who had experienced a hypoglycemic coma had a
significantly higher risk of ADHD (aHR = 6.54, 95% CI = 1.89-22.7) compared with
cohort without hypoglycemia. CONCLUSIONS: Hypoglycemia, especially hypoglycemic
coma, is significantly associated with a subsequent risk of ADHD in young people
with T1DM. This article is protected by copyright. All rights reserved.
PMID- 29938876
TI - Migraine disability complicated by medication overuse.
PMID- 29938877
TI - Neural representations of the body in 60-day-old human infants.
AB - The organization of body representations in the adult brain has been well
documented. Little is understood about this aspect of brain organization in human
infancy. The current study employed electroencephalography (EEG) with 60-day-old
infants to test the distribution of brain responses to tactile stimulation of
three different body parts: hand, foot, and lip. Analyses focused on a prominent
positive response occurring at 150-200 ms in the somatosensory evoked potential
at central and parietal electrode sites. The results show differential
electrophysiological signatures for touch of these three body parts. Stimulation
of the left hand was associated with greater positive amplitude over the lateral
central region contralateral to the side stimulated. Left foot stimulation was
associated with greater positivity over the midline parietal site. Stimulation of
the midline of the upper lip was associated with a strong bilateral response over
the central region. These findings provide new insights into the neural
representation of the body in infancy and shed light on research and theories
about the involvement of somatosensory cortex in infant imitation and social
perception.
PMID- 29938878
TI - The Existence of Nitrate Radicals in Irradiated TiO2 Aqueous Suspensions in the
Presence of Nitrate Ions.
AB - Evidence of the existence of nitrate radical in irradiated aqueous TiO2
suspensions in the presence of nitrate ions are reported for the first time. The
joint use of UV/Vis and EPR spectroscopy showed that nitrate radicals are formed
by hole induced oxidation of nitrate ions. Photocatalytic degradation of a model
alkene compound allowed to highlight the presence of an intermediate organic
nitrate deriving from nitrate radical attack to the double bond of the substrate.
These results not only allow deeper understanding of photocatalytic processes,
but open the route to new green photocatalytic syntheses initiated by nitrate
radicals and to new insights in the field of atmospheric chemistry.
PMID- 29938879
TI - A tale of two formulas: Differentiation of subtle anterior MI from benign ST
segment elevation.
AB - BACKGROUND: It may sometimes be difficult to differentiate subtle ST-segment
elevation (STE) due to anterior myocardial infarction (MI) from benign variant
(BV) STE. Recently, two related formulas were proposed for this purpose. However,
they have never been tested in an external population. MATERIALS AND METHODS:
Consecutive patients from May 2017 to January 2018, who were admitted with the
diagnosis of acute anterior STEMI, were enrolled. Electrocardiograms were
systematically reviewed and only subtle ones were included. First 200 consecutive
patients with noncardiac chest pain were also enrolled as a control group.
Relevant electrocardiographic parameters were measured. RESULTS: A total of 379
anterior MI and 200 BV-STE cases were enrolled during study period. A total of
241 patients in STEMI group were excluded for not matching subtleness criteria,
four patients in control group were also excluded because of prior left-anterior
descending artery intervention. The three-variable formula, with recommended cut
point of 23.5, had a sensitivity, specificity, and diagnostic accuracy of 73.9%,
86.7%, and 81.4%, respectively. The four-variable formula, with the published cut
point of 18.2, had a sensitivity, specificity, and diagnostic accuracy of 83.3%,
87.7%, and 85.9%, respectively. CONCLUSION: Three- and four-variable formulas
with recommended cutoffs have a reasonable sensitivity, specificity, and
diagnostic accuracy in differentiating subtle STEMI with BV-STE. Although both
perform well, the four-variable formula has a higher sensitivity, specificity,
and diagnostic accuracy and should be preferred.
PMID- 29938880
TI - Systematic review of the evidence for sustained efficacy of dietary interventions
for reducing appetite or energy intake.
AB - We assessed evidence for changes in efficacy of food-based interventions aimed at
reducing appetite or energy intake (EI), and whether this could be used to
provide guidance on trial design. A systematic search identified randomized
controlled trials testing sustained efficacy of diets, foods, supplements or food
ingredients on appetite and/or EI. Trials had to include sufficient exposure
duration (>=3 days) with appetite and/or EI measured after both acute and
repeated exposures. Twenty-six trials met the inclusion criteria and reported
data allowing for assessment of the acute and chronic effects of interventions.
Most (21/26) measured appetite outcomes and over half (14/26) had objective
measures of EI. A significant acute effect of the intervention was retained in 10
of 12 trials for appetite outcomes, and six of nine studies for EI. Initial
effects were most likely retained where these were more robust and studies
adequately powered. Where the initial, acute effect was not statistically
significant, a significant effect was later observed in only two of nine studies
for appetite and none of five studies for EI. Maintenance of intervention effects
on appetite or EI needs to be confirmed but seems likely where acute effects are
robust and replicable in adequately powered studies.
PMID- 29938881
TI - Animal Sound Identifier (ASI): software for automated identification of vocal
animals.
AB - Automated audio recording offers a powerful tool for acoustic monitoring schemes
of bird, bat, frog and other vocal organisms, but the lack of automated species
identification methods has made it difficult to fully utilise such data. We
developed Animal Sound Identifier (ASI), a MATLAB software that performs
probabilistic classification of species occurrences from field recordings. Unlike
most previous approaches, ASI locates training data directly from the field
recordings and thus avoids the need of pre-defined reference libraries. We apply
ASI to a case study on Amazonian birds, in which we classify the vocalisations of
14 species in 194 504 one-minute audio segments using in total two weeks of
expert time to construct, parameterise, and validate the classification models.
We compare the classification performance of ASI (with training templates
extracted automatically from field data) to that of monitoR (with training
templates extracted manually from the Xeno-Canto database), the results showing
ASI to have substantially higher recall and precision rates.
PMID- 29938882
TI - Competition and coexistence in plant communities: intraspecific competition is
stronger than interspecific competition.
AB - Theory predicts that intraspecific competition should be stronger than
interspecific competition for any pair of stably coexisting species, yet previous
literature reviews found little support for this pattern. We screened over 5400
publications and identified 39 studies that quantified phenomenological
intraspecific and interspecific interactions in terrestrial plant communities. Of
the 67% of species pairs in which both intra- and interspecific effects were
negative (competitive), intraspecific competition was, on average, four to five
fold stronger than interspecific competition. Of the remaining pairs, 93%
featured intraspecific competition and interspecific facilitation, a situation
that stabilises coexistence. The difference between intra- and interspecific
effects tended to be larger in observational than experimental data sets, in
field than greenhouse studies, and in studies that quantified population growth
over the full life cycle rather than single fitness components. Our results imply
that processes promoting stable coexistence at local scales are common and
consequential across terrestrial plant communities.
PMID- 29938883
TI - Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2
inhibitors on the risk of hospitalization for heart failure and amputation in
patients with type 2 diabetes mellitus: A real-world meta-analysis of 4
observational databases (OBSERVE-4D).
AB - AIMS: Sodium glucose co-transporter 2 inhibitors (SGLT2i) are indicated for
treatment of type 2 diabetes mellitus (T2DM); some SGLT2i have reported
cardiovascular benefit, and some have reported risk of below-knee lower extremity
(BKLE) amputation. This study examined the real-world comparative effectiveness
within the SGLT2i class and compared with non-SGLT2i antihyperglycaemic agents.
MATERIALS AND METHODS: Data from 4 large US administrative claims databases were
used to characterize risk and provide population-level estimates of
canagliflozin's effects on hospitalization for heart failure (HHF) and BKLE
amputation vs other SGLT2i and non-SGLT2i in T2DM patients. Comparative analyses
using a propensity score-adjusted new-user cohort design examined relative
hazards of outcomes across all new users and a subpopulation with established
cardiovascular disease. RESULTS: Across the 4 databases (142 800 new users of
canagliflozin, 110 897 new users of other SGLT2i, 460 885 new users of non
SGLT2i), the meta-analytic hazard ratio estimate for HHF with canagliflozin vs
non-SGLT2i was 0.39 (95% CI, 0.26-0.60) in the on-treatment analysis. The
estimate for BKLE amputation with canagliflozin vs non-SGLT2i was 0.75 (95% CI,
0.40-1.41) in the on-treatment analysis and 1.01 (95% CI, 0.93-1.10) in the
intent-to-treat analysis. Effects in the subpopulation with established
cardiovascular disease were similar for both outcomes. No consistent differences
were observed between canagliflozin and other SGLT2i. CONCLUSIONS: In this large
comprehensive analysis, canagliflozin and other SGLT2i demonstrated HHF benefits
consistent with clinical trial data, but showed no increased risk of BKLE
amputation vs non-SGLT2i. HHF and BKLE amputation results were similar in the
subpopulation with established cardiovascular disease. This study helps further
characterize the potential benefits and harms of SGLT2i in routine clinical
practice to complement evidence from clinical trials and prior observational
studies.
PMID- 29938885
TI - Intrinsic Triple Order in A-site Columnar-Ordered Quadruple Perovskites: Proof of
Concept.
AB - There is an emerging topic in the science of perovskite materials: A-site
columnar-ordered A2 A'A''B4 O12 quadruple perovskites, which have an intrinsic
triple order at the A sites. However, in many examples reported so far, A' and
A'' cations are the same, and the intrinsic triple order is hidden. Here, we
investigate structural properties of Dy2 CuMnMn4 O12 (1) and Ho2 MnGaMn4 O12 (2)
by neutron and X-ray powder diffraction and prove the triple order at the A
sites. The cation distributions determined are [Ho2 ]A [Mn]A' [Ga0.66 Mn0.34 ]A''
[Mn3.66 Ga0.34 ]B O12 and [Dy2 ]A [Cu0.73 Mn0.27 ]A' [Mn0.80 Dy0.20 ]A'' [Mn1.89
Cu0.11 ]B1 [Mn2 ]B2 O12 . There are clear signatures of Jahn-Teller distortions
in 1 and 2, and the orbital pattern is combined with an original type of charge
ordering in 1. Columnar-ordered quadruple perovskites represent a new playground
to study complex interactions between different electronic degrees of freedom. No
long-range magnetic order was found in 2 by neutron diffraction, and its magnetic
properties in low fields are dominated by an impurity with negative magnetization
or magnetization reversal. On the other hand, 1 shows three magnetic transitions
at 21, 125, and 160 K.
PMID- 29938884
TI - Running on mixed fuel-dual agonistic approach of GLP-1 and GCG receptors leads to
beneficial impact on body weight and blood glucose control: A comparative study
between mice and non-human primates.
AB - AIM: We performed acute and chronic studies in healthy and diet-induced obese
animals using mouse-specific or monkey-specific dual GLP-1R/GCGR agonists to
investigate their effects on food intake, body weight, blood glucose control and
insulin secretion. The selective GLP-1R agonist liraglutide was used as
comparator. METHODS: The mouse-specific dual agonist and liraglutide were tested
in lean wild type, GLP-1R knockout and diet-induced obese mice at different
doses. A chronic study was performed in DIO mice to investigate the effect on
body weight, food consumption and total energy expenditure (TEE) in obese and
diabetic monkeys with a focus on body weight and energy intake. RESULTS: The
mouse-specific dual agonist and liraglutide similarly affected glycaemic control.
A higher loss in body weight was measured in dual agonist-treated obese mice. The
dual agonist significantly enhanced plasma glucose excursion in overnight fed GLP
1R-/- mice, probably reflecting a potent GCGR agonist activity. It increased TEE
and enhanced fat and carbohydrate oxidation, while liraglutide produced no effect
on TEE. In obese and diabetic monkeys, treatment with the monkey-specific dual
agonist reduced total energy intake to 60%-70% of baseline TEI during chronic
treatment. A decrease in body weight and significant improvement in glucose
tolerance was observed. CONCLUSIONS: In DIO mice and non-human primates, dual
agonists elicited robust glycaemic control, similar to the marketed GLP-1R
agonist, while eliciting greater effects on body weight. Results from DIO mice
suggest that the increase in TEE is caused not only by increased fat oxidation
but also by an increase in carbohydrate oxidation.
PMID- 29938886
TI - Modern-day palliative chemotherapy for metastatic colorectal cancer: does colonic
resection affect survival?
AB - BACKGROUND: Patients with metastatic colorectal cancer (mCRC) with surgically
incurable metastases would be recommended for palliative chemotherapy (PC). The
role of surgical intervention is debatable with no conclusive evidence for
routine primary tumour resection (PTR) or stoma creation. We aimed to study if
surgical intervention conferred a survival benefit in patients with mCRC who
received upfront systemic therapy. METHODS: A retrospective review of a
prospectively collected database in a single centre was performed. Patients
diagnosed with mCRC from January 2004 to December 2014 were included. We excluded
patients who had an upfront surgical intervention, had no treatment with systemic
therapy or had attained curative resection. The decision for surgery was based on
the outcome of a multidisciplinary tumour board. Demographic,
clinicopathological, treatment and follow-up data were collected. Univariate and
multivariate analyses were performed. RESULTS: Out of 408 patients with mCRC with
incurable metastases, we analysed 124 patients who had upfront PC. Twenty-nine
had PC + PTR (group A), 10 had PC + stoma (group B) and 85 had PC only (group C).
Undergoing PTR led to significant improvement in overall survival (OS; 30.8
versus 13.4 versus 11.0 months, P < 0.001). With multivariate analysis,
undergoing PTR and receiving biologics were independent good prognostic
variables. Surgical resection was safe with minimal complications. CONCLUSIONS:
PTR was found to increase OS while stoma creation had no impact on OS. The
benefits and safety of undergoing PTR may be a result of selection bias. Further
prospective studies are required to confirm the observations of this study.
PMID- 29938887
TI - Clinical outcomes in real-world patients with type 2 diabetes switching from
first- to second-generation basal insulin analogues: Comparative effectiveness of
insulin glargine 300 units/mL and insulin degludec in the DELIVER D+ cohort
study.
AB - AIMS: To compare clinical outcomes in patients with type 2 diabetes (T2D)
switching from insulin glargine 100 units/mL (Gla-100) or insulin detemir (IDet)
to insulin glargine 300 units/mL (Gla-300) or insulin degludec (IDeg). MATERIALS
AND METHODS: We conducted a retrospective, observational study of electronic
medical records for Gla-300/IDeg adult switchers (March 1, 2015 to January 31,
2017) with active records for 12-month baseline (glycated haemoglobin [HbA1c]
used a 6-month baseline period) and 6-month follow-up periods. Gla-300 and IDeg
switchers were propensity score-matched using baseline demographic and clinical
characteristics. Outcomes were HbA1c change and goal attainment (among patients
with HbA1c captured at follow-up), and hypoglycaemia with fixed follow-up
(intention-to-treat [ITT]; 6 months) and variable follow-up (on-treatment [OT];
to discontinuation or 6 months). RESULTS: Each matched cohort comprised 1592
patients. The mean decrease in HbA1c and HbA1c goal (<7.0% [53 mmol/mol] and
<8.0% [64 mmol/mol]) attainment rates were similar for Gla-300 (n = 742) and IDeg
(n = 727) switchers. Using fixed follow-up (ITT method), hypoglycaemia incidence
decreased significantly from baseline with Gla-300 (all hypoglycaemia: 15.6% to
12.7%; P = .006; hypoglycaemia associated with inpatient/emergency department
[ED] encounter: 5.3% to 3.5%; P = .007), but not with IDeg. After adjusting for
baseline hypoglycaemia, no significant differences in hypoglycaemia incidence and
event rate were found at follow-up (ITT) for Gla-300 vs IDeg. Using variable
follow-up (OT), hypoglycaemia incidence was similar in both groups, but Gla-300
switchers had a lower inpatient/ED hypoglycaemia event rate at follow-up
(adjusted rate ratio 0.56; P = .016). CONCLUSIONS: In a real-world setting,
switching from Gla-100 or IDet to Gla-300 or IDeg was associated with similar
improvements in glycaemic control and hypoglycaemia in adult patients with T2D.
PMID- 29938888
TI - Global dung webs: high trophic generalism of dung beetles along the latitudinal
diversity gradient.
AB - At the global scale, species diversity is known to strongly increase towards the
equator for most taxa. According to theory, a higher resource specificity of
consumers facilitates the coexistence of a larger number of species and has been
suggested as an explanation for the latitudinal diversity gradient. However, only
few studies support the predicted increase in specialisation or even showed
opposite results. Surprisingly, analyses for detritivores are still missing.
Therefore, we performed an analysis on the degree of trophic specialisation of
dung beetles. We summarised 45 studies, covering the resource preferences of a
total of 994503 individuals, to calculate the dung specificity in each study
region. Our results highlighted a significant (4.3-fold) increase in the
diversity of beetles attracted to vertebrate dung towards the equator. However,
their resource specificity was low, unrelated to diversity and revealed a highly
generalistic use of dung resources that remained similar along the latitudinal
gradient.
PMID- 29938889
TI - Carryover effects from natal habitat type upon competitive ability lead to trait
divergence or source-sink dynamics.
AB - Local adaptation to rare habitats is difficult due to gene flow, but can occur if
the habitat has higher productivity. Differences in offspring phenotypes have
attracted little attention in this context. We model a scenario where the rarer
habitat improves offspring's later competitive ability - a carryover effect that
operates on top of local adaptation to one or the other habitat type. Assuming
localised dispersal, so the offspring tend to settle in similar habitat to the
natal type, the superior competitive ability of offspring remaining in the rarer
habitat hampers immigration from the majority habitat. This initiates a positive
feedback between local adaptation and trait divergence, which can thereafter be
reinforced by coevolution with dispersal traits that match ecotype to habitat
type. Rarity strengthens selection on dispersal traits and promotes linkage
disequilibrium between locally adapted traits and ecotype-habitat matching
dispersal. We propose that carryover effects may initiate isolation by ecology.
PMID- 29938890
TI - Switching the Statistical C3 /C1 Ratio in the Threefold Aromatic Substitution of
Tribenzotriquinacenes towards the C3 Isomer.
AB - Tribenzotriquinacene (TBTQ) is a bowl-shaped molecule that has been widely used
as a molecular building block in supramolecular and materials chemistry.
Especially C3 -symmetric threefold-substituted TBTQs are interesting for these
purposes. Until now a general and selective synthetic approach to those C3
symmetric products was lacking, mainly because the typically used electrophilic
aromatic substitution reactions of the parent TBTQ hydrocarbons produce
predominantly the C1 isomer over the C3 isomer (3:1 statistical ratio). Herein we
introduce a threefold borylation of TBTQ with the C3 isomer as the main product
(2.6:1 C3 /C1 ratio). The borylated TBTQ can be converted in good yields into
other C3 -symmetric TBTQs, thus allowing straightforward synthetic access to new
building blocks for supramolecular and materials chemistry.
PMID- 29938892
TI - Perceptual and arterial occlusion responses to very low load blood flow
restricted exercise performed to volitional failure.
AB - PURPOSE: Studies examining perceptual and arterial occlusion responses between
blood flow restricted exercise and high load exercise often prescribe an
arbitrary number of repetitions, making it difficult for direct comparisons.
Therefore, the purpose of this study was to compare these protocols when
performed to volitional failure. METHODS: Individuals completed four exercise
conditions varying in load and pressure: (i) 15% 1RM; no restrictive pressure,
(ii) 15% 1RM; 40% arterial occlusion pressure, (iii) 15% 1RM; 80% arterial
occlusion pressure, and (iv) 70% 1RM; no pressure. Four sets of knee extension
exercises were performed until volitional failure (or until 90 repetitions per
set) was completed. RESULTS: A total of 23 individuals completed the study. While
all conditions increased arterial occlusion pressure, the greatest increases
(~30%) were observed in the blood flow restriction conditions. All lower load
conditions resulted in greater RPE and discomfort than that of the high load
condition, but only discomfort was increased further when adding blood flow
restriction. CONCLUSION: High load exercise will likely be perceived more
favourably than lower load exercise to volitional failure; however, those who are
incapable or unwilling to lift heavier loads may use blood flow restriction to
help reduce the volume needed to reach volitional failure, although this will
likely increase discomfort.
PMID- 29938893
TI - Toxicology Meets Pharmacodynamics and Pharmacokinetics - New Concepts, Models and
In Vitro Approaches and Tools.
PMID- 29938891
TI - Measuring beverage consumption in US children and adolescents: a systematic
review.
AB - Beverage consumption habits are associated with weight outcomes for children and
adolescents. Many studies have examined youth's beverage consumption, but little
is known about what methods are commonly used to assess youth beverage
consumption and whether these strategies are valid and reliable. This study aimed
to systematically review articles assessing beverage consumption among children
and adolescents. We searched PubMed and Scopus for English-language articles
published between February 2007 and February 2017 that measured and reported on
American youth's (ages 2-18 years) beverage consumption. Searches yielded 17,165
articles, of which 589 articles describing 615 measures were extracted. We
examined the types of assessment methods used, characteristics of these methods
(e.g. validity, reliability, and literacy level), characteristics of study
samples, and beverages assessed. The most common assessment methods were
questionnaires/screeners (used by 65.4% of articles) and recalls (24.4%). About
three-quarters of articles did not address validity (70.5%) or reliability
(79.5%) of any measures used. Study populations were diverse: 54.7% of articles
included low-income children, and 90.2% included non-White children. The most
commonly assessed beverage category was sugar-sweetened beverages. Findings
suggest that improved measurement techniques and reporting are both needed to
track progress towards a goal of ensuring all youth have healthy beverage
consumption.
PMID- 29938894
TI - Erythematous-violaceous plaques on the trunk and extremities of a child.
PMID- 29938895
TI - IgG4-related disease with skin, submaxillary and pulmonary involvement.
PMID- 29938896
TI - Expansion microscopy: enabling single cell analysis in intact biological systems.
AB - There is a need for single cell analysis methods that enable the identification
and localization of different kinds of biomolecules throughout cells and intact
tissues, thereby allowing characterization and classification of individual cells
and their relationships to each other within intact systems. Expansion microscopy
(ExM) is a technology that physically magnifies tissues in an isotropic way,
thereby achieving super-resolution microscopy on diffraction-limited microscopes,
enabling rapid image acquisition and large field of view. As a result, ExM is
well-positioned to integrate molecular content and cellular morphology, with the
spatial precision sufficient to resolve individual biological building blocks,
and the scale and accessibility required to deploy over extended 3-D objects like
tissues and organs.
PMID- 29938897
TI - 34-year-old patient with blackish macules on the dorsa of the hands and forearms.
PMID- 29938898
TI - Offset Analgesia and The Impact of Treatment with Oxycodone and Venlafaxine: A
Placebo-Controlled, Randomized Trial in Healthy Volunteers.
AB - Offset analgesia (OA) is a pain-modulating mechanism described as a
disproportionately large decrease in pain intensity evoked by a discrete decrease
in stimulus temperature. The role of the opioidergic, serotonergic and
noradrenergic systems on OA remains unclear. The aim of this study was to
evaluate whether OA is modulated by an opioid (oxycodone) and a serotonin and
noradrenaline reuptake inhibitor (venlafaxine) in terms of psychophysical
assessments. In this randomized, double-blinded, placebo-controlled cross-over
study, 20 healthy male participants (mean age: 24.6 +/- 2.5 years) received 10 mg
oxycodone, 37.5 mg venlafaxine or placebo twice daily for 5 days in three
periods. OA was induced by noxious thermal stimulation on the forearm at baseline
and last day of treatment. A control session of constant stimulus intensity was
included for comparison. OA magnitude was unaffected by oxycodone and venlafaxine
(p = 0.20 and p = 0.90, respectively). Oxycodone affected the control paradigm
where a decreased rating of pain intensity was observed compared to placebo (p =
0.001). OA could not be modulated by oxycodone or venlafaxine and may be a robust
phenomenon in healthy volunteers and not suitable for exploring pharmacological
mechanisms of analgesia in human beings.
PMID- 29938899
TI - Plant phenolics mediated bottom-up effects of elevated CO2 on Acyrthosiphon pisum
and its parasitoid Aphidius avenae.
AB - Elevated concentrations of atmospheric CO2 can alter plant secondary metabolites,
which play important roles in the interactions among plants, herbivorous insects
and natural enemies. However, few studies have examined the cascading effects of
host plant secondary metabolites on tri-trophic interactions under elevated CO2
(eCO2 ). In this study, we determined the effects of eCO2 on the growth and
foliar phenolics of Medicago truncatula and the cascading effects on two color
genotypes of Acyrthosiphon pisum (pink vs. green) and their parasitoid Aphidius
avenae in the field open-top chambers. Our results showed that eCO2 increased
photosynthetic rate, nodule number, yield and the total phenolic content of M.
truncatula. eCO2 had contrasting effects on two genotypes of A. pisum; the green
genotype demonstrated increased population abundance, fecundity, growth and
feeding efficiency, while the pink genotype showed decreased fitness and these
were closely associated with the foliar genstein content. Furthermore, eCO2
decreased the parasitic rate of A. avenae independent of aphid genotypes. eCO2
prolonged the emergence time and reduced the emergence rate and percentage of
females when associated with the green genotype, but little difference, except
for increased percentage of females, was observed in A. avenae under eCO2 when
associated with the pink genotype, indicating that parasitoids can perceive and
discriminate the qualities of aphid hosts. We concluded that eCO2 altered plant
phenolics and thus the performance of aphids and parasitoids. Our results
indicate that plant phenolics vary by different abiotic and biotic stimuli and
could potentially deliver the cascading effects of eCO2 to the higher trophic
levels. Our results also suggest that the green genotype is expected to perform
better in future eCO2 because of decreased plant resistance after its infestation
and decreased parasitic rate.
PMID- 29938900
TI - Novel Mechanism of Fatty Acid Sensing in Enteroendocrine Cells: Specific
Structures in Oxo-Fatty Acids Produced by Gut Bacteria Are Responsible for CCK
Secretion in STC-1 Cells via GPR40.
AB - SCOPE: The secretion of gut hormones, such as cholecystokinin (CCK) is stimulated
by fatty acids. Although a chain length-dependent mechanism has been proposed,
other structural relationships to releasing activity remain unclear. We aimed to
elucidate specific structures in fatty acids that are responsible for their CCK
releasing activity, and related sensing mechanisms in enteroendocrine cells.
METHODS AND RESULTS: CCK secretory activities were examined in a murine CCK
producing cell line STC-1 by exposing the cells to various modified fatty acids
produced by gut lactic acid bacteria. The effects of fatty acids on gastric
emptying rate as a CCK-mediated function were examined using acetaminophen and
phenol red methods in rats. Out of more than 30 octadecanoic-derived fatty acids
tested, 5 oxo-fatty acids potently stimulated CCK secretion without cytotoxic
effects in STC-1 cells. Three fatty acids had a distinct specific structure
containing one double bond, whereas the other two had two double bonds, nearby an
oxo residue. CCK secretion induced by representative fatty acids (10-oxo-trans-11
18:1 and 13-oxo-cis-9,cis-15-18:2) was attenuated by a fatty acid receptor G
protein coupled receptor 40 antagonist. Oral administration of 13-oxo-cis-9,cis
15-18:2 lowered the gastric emptying rate in rats in a dose- and structure
dependent manner. CONCLUSION: These results reveal a novel fatty acid-sensing
mechanism in enteroendocrine cells.
PMID- 29938901
TI - Physical activity modulates arterial stiffness in children with congenital heart
disease: A CHAMPS cohort study.
AB - : Children with congenital heart disease are at risk for developing increased
arterial stiffness and this may be modulated by physical activity. OBJECTIVE: To
compare arterial stiffness in high- and low-physically active children with
congenital heart disease and healthy age- and sex-matched controls. PATIENTS:
Seventeen children with congenital heart disease (12 +/- 2 years; females = 9),
grouped by low- and high-physical activity levels from accelerometry step count
values, and 20 matched controls (11 +/- 3 years; females = 9) were studied.
OUTCOME MEASURES: Carotid-radial pulse wave velocity was assessed with
applanation tonometry to determine arterial stiffness. Body composition and 6-min
walk test measures were performed. Data were analyzed using analysis of variance
and multiple regression. Significance was P < .05. RESULTS: Arterial stiffness
was increased in low-physically active children with congenital heart disease
(9.79 +/- 0.97 m/s) compared to high-physically active children with congenital
heart disease (7.88 +/- 0.71 m/s; P = .002) and healthy-matched controls (8.67 +/
1.28 m/s; P = .015). There were no differences in body composition measures
between groups (all P > .05), but 6-min walk test distance was less in both
congenital heart disease groups (high-physically active: 514 +/- 40 m; low
physically active: 539 +/- 49 m) versus controls (605 +/- 79 m; all P < .05).
Average daily step count significantly predicted arterial stiffness in children
with congenital heart disease (R2 = 0.358) with a negative correlation (R =
0.599, P = .011), while % fat mass (P = .519) and % lean mass (P = .290) did not
predict arterial stiffness. CONCLUSIONS: Low-physically active children with
congenital heart disease have increased arterial stiffness compared to high
physically active children with congenital heart disease and healthy-matched
controls. Regular physical activity in children with congenital heart disease may
modulate arterial stiffness.
PMID- 29938902
TI - Psychosocial distress and desire for support among skin cancer patients - impact
of treatment setting.
AB - BACKGROUND: Diagnosis and treatment of malignancies are frequently associated
with a variety of problems for affected individuals and their relatives. In order
to ensure adequate psycho-oncological and social care, it is recommended to
routinely assess patients' psychosocial distress. While psychosocial services for
inpatients have been expanded in recent years, the outpatient care structure in
terms of psycho-oncological support is far from satisfactory, especially in
Mecklenburg-Western Pomerania. We therefore set out to investigate the following
questions: Does the need for psychosocial care vary in relation to (a) the
treatment setting (inpatients vs. outpatients) and (b) the diagnosis? (c) Do
patients experiencing psychological distress desire support? PATIENTS AND
METHODS: We asked both inpatients and outpatients to rate their psychosocial
situation using the Hornheide Questionnaire. Patients were also asked about their
desire for psychological support and the preferred contact person. RESULTS: (a)
The treatment setting had no impact on the need for psychosocial care and the
desire for support. (b) Depending on the type of skin cancer, there were
significant differences in the need for such care among the 251 patients
surveyed. (c) Despite a certain discrepancy, there was a significant correlation
between psychosocial distress (39.0 %; n = 98/251) and desire for support (14.3
%; n = 35/245). (d) Patients experiencing distress primarily chose physicians (n
= 21) and psychologists (n = 20) as potential contact persons. CONCLUSIONS: (1)
In addition to the level of distress, the desire for support should be inquired.
(2) Recommendations by physicians represent an important means of access to
psycho-oncological services. (3) Services for outpatient support should be
expanded.
PMID- 29938903
TI - Fermented Soybean Suppresses Visceral Fat Accumulation in Mice.
AB - SCOPE: Mice are fed a soybean diet before or after fermentation in the present
work to allow direct comparison of the antiobesity effect of fermentation.
METHODS: C57BL6J mice were fed high-fat diets containing boiled soybeans
(prefermentation) or Natto (postfermentation) for 4 weeks. Prefermented cooked
soybeans or Natto was added at levels of 2.5 and 5%, which are the amounts that
can be ingested in a normal diet once and twice a day. In addition, mice gut
microbiota from fecal samples were analyzed to explore the mechanisms of effects
caused by fermentation. RESULTS: Natto intake significantly reduced visceral fat
in a dose-dependent manner, inhibited hypertrophy of adipocytes, improved
carbohydrate metabolism, and reduced oxidative stress. These effects were seen in
mice fed soybeans before fermentation, but were stronger in mice fed Natto.
Therefore, soybean intake has beneficial effects and fermentation of soybeans
enhances these effects. Natto was found to suppress fatty acid synthesis and
promote fatty acid catabolism in the liver. These effects were also stronger with
Natto compared with soybeans before fermentation. In addition, Natto had more
potent beneficial effects on gut microbiota compared to soybeans. CONCLUSIONS:
These results suggest that Natto intake supports maintenance of health.
PMID- 29938904
TI - Experimental and theoretical study between cefoxitin and Escherichia coli 5
protein on selection of bioactive molecules against resistant strain.
AB - The Penicillin Binding Proteins (PBPs) are important biological target for new
antibacterial drugs development. This study focused on molecular interaction
between cefoxitin and the Escherichia coli PBP5 by molecular dynamics (MD) by
using hybrid quantum mechanics/molecular mechanics (QM/MM) simulations approach,
searching to develop a computational simulations prototype method on
antimicrobial susceptibility of gram-negative bacteria against antibiotics. E.
coli ATCC 8739 strain susceptibility for the drugs used in the antimicrobial
susceptibility testing and selection of bioactive molecules against resistant
strain. The protonation revealed a deprotonate state for His146, His151, His216
and His320 residues. The complex was stabilized after 0.6 ns of MD simulation.
The global interaction means for inhibition zone diameters of E. coli ATCC8739
strain and cefoxitin was 24.33 mm no showing significant difference between
computational and experimental methods. Our computational simulation method can
reliably be performed as a molecular modeling prototype for gram-negative
antimicrobial susceptibility testing bacteria. This article is protected by
copyright. All rights reserved.
PMID- 29938905
TI - CRISPR/Cas9-based mutation reveals Argonaute 1 is essential for pigmentation in
Ostrinia furnacalis.
AB - Ostrinia furnacalis (Lepidoptera: Pyralidae) is one of the most destructive
agricultural pests in Asia. Traditional pest-management methods include sex
pheromone capture, transgenic crops that produce Bacillus thuringiensis toxin,
and pesticides. Although these strategies control pest populations effectively,
they also cause negative side effects, including dramatically increased pesticide
resistance, severe pollution, and hazards for human health. Recently developed
genome editing tools provide new prospects for pest management and have been
successfully used in several species. However, few examples have been reported in
the agricultural pest O. furnacalis due to a lack in genomic information. In this
report, we identified only one transcript of O. furnacalis Argonaute 1 (OfAgo1)
gene from the genome and cloned the open reading frame. OfAgo1 presented the
maximum expression at the embryo stage or in the fat body during the larval
stages. To understand its function, an OfAgo1 mutant was constructed using the
Clustered Regularly Interspaced Short Palindromic Repeat/RNA-guided Cas9 nuclease
(CRISPR/Cas9). Mutagenesis of OfAgo1 disrupted cuticle pigmentation by down
regulating micro RNAs and pigmentation-related genes. This is the first report
for the cloning and functional analysis of OfAgo1, revealing a role of OfAgo1 in
cuticle pigmentation. The current report also established a CRISPR/Cas9 system in
O. furnacalis, providing a new insight for pest management.
PMID- 29938906
TI - Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein
Synthesis but Activated Autophagy during Anorexia-Induced Malnutrition in Mice.
AB - Anorexia nervosa is an eating disorder often associated with intestinal
disorders. To explore the underlying mechanisms of these disorders, the colonic
proteome was evaluated during activity-based anorexia. Female C57Bl/6 mice were
randomized into three groups: Control, Limited Food Access (LFA) and Activity
Based Anorexia (ABA). LFA and ABA mice had a progressive limited access to food
but only ABA mice had access to an activity wheel. On colonic mucosal protein
extracts, a 2D PAGE-based comparative proteomic analysis was then performed and
differentially expressed proteins were identified by LC-ESI-MS/MS. Twenty-seven
nonredundant proteins that were differentially expressed between Control, LFA,
and ABA groups were identified. ABA mice exhibited alteration of several
mitochondrial proteins involved in energy metabolism such as dihydrolipoyl
dehydrogenase and 3-mercaptopyruvate sulfurtransferase. In addition, a
downregulation of mammalian target of rapamycin (mTOR) pathway was observed
leading, on the one hand, to the inhibition of protein synthesis, evaluated by
puromycin incorporation and mediated by the increased phosphorylation of
eukaryotic elongation factor 2, and on the other hand, to the activation of
autophagy, assessed by the increase of the marker of autophagy, form LC3
phosphatidylethanolamine conjugate/Cytosolic form of Microtubule-associated
protein 1A/1B light chain 3 (LC3II/LC3I) ratio. Colonic mucosal proteome is
altered during ABA suggesting a downregulation of energy metabolism. A decrease
of protein synthesis and an activation of autophagy were also observed mediated
by mTOR pathway.
PMID- 29938907
TI - Inter-arm systolic blood pressure dependence on hand dominance.
AB - Inter-arm systolic blood pressure differences (SBP-DIFF) >= 10 mmHg have been
reported useful to predict future cardiovascular-related morbidities. Although
well studied in patients, there is little information on healthy young adults and
the role of hand-dominance as a factor affecting SBP-DIFF. As dominant arms (DOM)
tend to have greater girth and muscle development than nondominant arms (NDOM) it
was reasoned that cuff pressures needed to obtain SBP may be greater on DOM
causing DOM SBP to be greater. To test this hypothesis and also provide typical
values, SBP was measured in left and right-handers (29.4 +/- 10.4 years) in whom
handedness was clearly defined. Handedness was determined by a multi-question
form in 90 young adults (45 male) and SBP-DIFF determined via simultaneous
measurements done in triplicate on seated subjects. The percentage of left
handers in male and female sub-groups were equal at 37.8%. Results show that the
absolute SBP-DIFF in left-handers (mean +/- SD) was 4.4 +/- 3.8 mmHg and for
right-handers was 5.0 +/- 4.2 mmHg (P = 0.362). There was also no statistically
significant difference among 1st, 2nd and 3rd measured SBP-DIFF for either right
or left-handers or differences between right and left-handers. Results show no
evidence of a higher SBP in DOM and thus clarifies the hand-dominance issue as a
factor not generally needing to be considered in clinical assessments. A
potentially useful secondary outcome was the finding that 14.8% of this group had
at least one measured SBP-DIFF >= 10 mmHg a fact that may have future relevance.
PMID- 29938908
TI - Atypical Antipsychotic Administration in Schizophrenic Patients Leads to Elevated
Lipoprotein-Associated Phospholipase A2 Levels and Increased Cardiovascular Risk:
A Retrospective Cohort Study.
AB - The prevalence of cardiovascular disease (CVD) is higher in patients with
schizophrenia than in the general population. We aimed to investigate whether
atypical antipsychotics (AAP) increase the levels of lipoprotein-associated
phospholipase A2 (Lp-PLA2), thereby increasing the risk of CVD. The data were
from inpatients aged 18-60 years with a diagnosis of schizophrenia according to
ICD-10 at the Affiliated Brain Hospital of Nanjing Medical University who
underwent physical examination between 1 October 2014 and 30 September 2016. A
retrospective cohort study was used to analyse the correlation between AAP, Lp
PLA2 levels and the CVD risk (it was determined that Lp-PLA2 values >200 ng/mL
were defined as high CVD risk) in patients treated with monotherapy, olanzapine,
clozapine or quetiapine. Data were collected for 452 patients with eligible
schizophrenia: 163 treated with clozapine, 186 treated with olanzapine, 47
treated with quetiapine and 56 receiving no medication. Compared with the no
medication patients, AAP administration in patients with olanzapine, clozapine or
quetiapine had higher serum Lp-PLA2 levels when age, sex, BMI and fasting glucose
level were matched. AAP were significantly associated with serum Lp-PLA2 level by
Spearman's correlation coefficients. The results of logistic regression analysis
showed that AAP administration was an independent factor of CVD risk when
adjusted by potential confounding factors. This study is the first to confirm
that AAP administration, especially clozapine and olanzapine, could increase Lp
PLA2 levels and CVD risk, independent of drug-induced weight gain in
schizophrenia. The extent and the factors of increasing Lp-PLA2 level and CVD
risk in olanzapine, clozapine and quetiapine are discrepant. The possible effects
of AAP on Lp-PLA2 in schizophrenia patients are involved in pro-inflammatory
cytokines and hormones.
PMID- 29938909
TI - The role of regional prenatal cardiac screening for congenital heart disease: A
single center experience.
AB - BACKGROUND: Accurate prenatal diagnosis of congenital heart disease (CHD) allows
for appropriate delivery and postnatal management. Geographic constraints limit
access to fetal cardiology subspecialists. In our approach, general pediatric
cardiologists are first line in regional prenatal cardiac screening. We aim to
demonstrate the utility of this approach in diagnosing CHD requiring cardiac
interventions within 30 days of life. METHODS: This is a retrospective review of
fetal echocardiograms performed at Seattle Children's Hospital regional
cardiology sites (SCH-RC) from December 2008 to December 2015. Referrals to
Seattle Children's Hospital Prenatal Program (SCH-PNP) were evaluated for
referral timing, indication, diagnostic accuracy, and postnatal care. Diagnostic
accuracy was determined using the initial postnatal echocardiogram as the gold
standard. Major discrepancy was defined as one resulting in change in surgical
management. RESULTS: Of 699 fetuses evaluated at regional sites throughout
Washington and Alaska, a small subset (n = 48; 6.9%) required referral to SCH
PNP. Need for relocation was confirmed in 31 subjects, of which 27 required
cardiac intervention within 30 days of life. Of those not referred to SCH-PNP (n
= 643, 91.9%), none required neonatal cardiac intervention. There were 22
regional diagnostic discrepancies (31% major, 7% minor). Referral to SCH-PNP
improved diagnostic accuracy (2% major, 0% minor). CONCLUSIONS: Regional prenatal
cardiac screening demonstrated 100% sensitivity and 98.9% specificity for
identifying critical CHD. Utilizing regional pediatric cardiologists as first
line in prenatal screening in geographically remote regions may improve access to
care and outcomes in neonates with critical CHD while improving resource
utilization.
PMID- 29938910
TI - Interventions and social functioning in youth at risk of psychosis: A systematic
review and meta-analysis.
AB - AIM: Youth at clinical high risk (CHR) for psychosis often exhibit difficulties
in social functioning and poorer social functioning may be predictive of
transition to a psychotic disorder. Therefore, the primary objective of this
systematic review was to summarize the impact of all interventions on social
functioning in CHR samples. METHOD: Electronic databases PsycINFO, CINAHL,
Embase, EBM, and MEDLINE were searched from 1951 to June 2017. Studies were
selected if they included any intervention that reported changes in social
functioning in youth at CHR. Data were evaluated using random effects pairwise
meta-analyses, stratified by time, and reported as the standardized mean
difference (SMD). RESULTS: Nineteen studies met our inclusion criteria, including
a total of 1513 CHR participants. The mean age was 20.5 years and 47% were male.
Cognitive behavioural therapy (4 studies) did not significantly improve social
functioning at 6 months (SMD = 0.06; 95% confidence interval [CI] = -0.35, 0.46),
12 months (SMD = -0.15; 95% CI = -0.38, 0.08) and 18 months (SMD = 0.20; 95% CI =
-0.10, 0.50). Omega-3 (2 studies) did not significantly improve social
functioning at 6 months (SMD = 0.01; 95% CI = -0.21, 0.24) and 12 months (SMD =
0.08; 95% CI = -0.33, 0.17). Lastly, cognitive remediation (3 studies) did not
significantly improve social functioning at 2- to 3-month follow-up (SMD = 0.13,
95% CI = -0.18, 0.43). CONCLUSIONS: This systematic review and meta-analysis
demonstrated that no treatment significantly improved social functioning in youth
at CHR. Future randomized control trials are required that are designed to target
and improve social functioning in youth at CHR for psychosis.
PMID- 29938911
TI - Clinicopathological profile of paroxysmal nocturnal haemoglobinuria clone
positive aplastic anaemia paediatric patients-A single centre study from North
India.
AB - INTRODUCTION: There is a paucity of literature related to the prevalence of
Paroxysmal Nocturnal haemoglobinuria (PNH) clones in paediatric aplastic anaemia
(AA) patients. METHODS: We performed a retrospective analysis over a period of 42
months to study the prevalence of PNH clones in paediatric (age less than 18
years) AA cases, using Fluorescein-labelled proaerolysin-based flow cytometric
screening and analysed their clinico-pathological features. RESULTS: PNH clone
was identified in 100 (33.2%) of the 301 patients screened. These were comprised
of 51 cases of non-severe AA, 33 cases of severe AA and 16 cases of very severe
AA. The median age was 13 years with an M:F ratio of 2.5:1. The median clone size
(taken as the proportion of PNH-positive neutrophils) was 2.15% (range: 0.05%
93.1%). Although a majority of patients (n = 77) had a clone size of less than
10%, a significant proportion (n = 23) did harbour a clone size of more than 10%.
Evidence of haemolysis was observed in 3 patients, all of them having a clone
size of more than 10%. Interestingly, 1 patient with dural sinus thrombosis
harboured a clone size of 1.25% only. Chromosomal breakage analysis was performed
in 61 patients, none of which was positive. Complete and partial response to
immunosuppressive therapy was found in 55.1% patients (16/29). CONCLUSION: There
is a high prevalence of PNH clones in paediatric AA patients, which in a majority
of cases are of small clone sizes. The use of immunosuppressive therapy does not
show a better outcome as compared to PNH-negative cases.
PMID- 29938912
TI - The second life of ion transporters as signal transducers.
PMID- 29938913
TI - Pigmentation abnormalities in nucleotide excision repair disorders: Evidence and
hypotheses.
AB - Skin pigmentation abnormalities are manifested in several disorders associated
with deficient DNA repair mechanisms such as nucleotide excision repair (NER) and
double-strand break (DSB) diseases, a topic that has not received much attention
up to now. Hereditary disorders associated with defective DNA repair are valuable
models for understanding mechanisms that lead to hypo- and hyperpigmentation.
Owing to the UV-associated nature of abnormal pigmentary manifestations, the
outcome of the activated DNA damage response (DDR) network could be the effector
signal for alterations in pigmentation, ultimately manifesting as pigmentary
abnormalities in repair-deficient disorders. In this review, the role of the DDR
network in the manifestation of pigmentary abnormalities in NER and DSB disorders
is discussed with a special emphasis on NER disorders.
PMID- 29938914
TI - Population-representative analysis of dietary supplementation among Americans
with diabetes mellitus.
AB - BACKGROUND: Few population-representative studies have examined dietary
supplement use among Americans with diabetes mellitus (DM). This investigation
analyzed dietary supplementation and DM data from the 2013-2014 National Health
and Nutrition Examination Survey (NHANES). METHODS: Data from 5040 adult
participants were analyzed, including 639 participants reporting a diagnosis of
DM (Method 1), which increased to 1036 after including participants reporting
"borderline" DM or prediabetes (Method 2). Participants reported dietary
supplements used over the past month. The prevalence of supplementation was
compared among participants with and without DM using the Rao-Scott likelihood
Chi-squared test; multivariate logistic regression was used to examine whether DM
was an independent predictor of supplementation. RESULTS: Regardless of whether
Method 1 or Method 2 was used, dietary supplementation was more prevalent among
participants with DM (Method 1, 61.4% vs. 54.4%, P = 0.024; Method 2, 62.7% vs.
53.5%, P < 0.001). After adjusting for a variety of demographic and health
related variables, the presence of DM was no longer associated with
supplementation for Method 1 (odds ratio [OR] 1.01; 95% confidence interval [CI]
0.78-1.32; P = 0.925) or Method 2 (OR 1.13; 95% CI 0.91-1.41; P = 0.238).
Approximately four of every five products taken for the purpose of managing DM
were self-prescribed, the most common being multivitamins-minerals, cinnamon
containing supplements, and chromium-containing supplements. CONCLUSIONS:
Slightly more than six out of 10 Americans with DM use dietary supplements each
month and, although this is higher than Americans without DM, it does not appear
to be due to DM per se.
PMID- 29938915
TI - IGF-1 in exercise-induced enhancement of episodic memory.
PMID- 29938916
TI - Bioinspired Mineral-Organic Bioresorbable Bone Adhesive.
AB - Bioresorbable bone adhesives have potential to revolutionize the clinical
treatment of the human skeletal system, ranging from the fixation and
osteointegration of permanent implants to the direct healing and fusion of bones
without permanent fixation hardware. Despite an unmet need, there are currently
no bone adhesives in clinical use that provide a strong enough bond to wet bone
while possessing good osteointegration and bioresorbability. Inspired by the
sandcastle worm that creates a protective tubular shell around its body using a
proteinaceous adhesive, a novel bone adhesive is introduced, based on
tetracalcium phosphate and phosphoserine, that cures in minutes in an aqueous
environment and provides high bone-to-bone adhesive strength. The new material is
measured to be 10 times more adhesive than bioresorbable calcium phosphate cement
and 7.5 times more adhesive than non-resorbable poly(methyl methacrylate) bone
cement, both of which are standard of care in the clinic today. The bone adhesive
also demonstrates chemical adhesion to titanium approximately twice that of its
adhesion to bone, unlocking the potential for adherence to metallic implants
during surrounding bony incorporation. Finally, the bone adhesive is shown to
demonstrate osteointegration and bioresorbability over a 52-week period in a
critically sized distal femur defect in rabbits.
PMID- 29938917
TI - Exogenous/Endogenous-Triggered Mesoporous Silica Cancer Nanomedicine.
AB - Recent advances in nanomedicine-based theranostic platforms have catalyzed the
generation of new theranostic modalities for pathological abnormalities, such as
cancer. Mesoporous silica-based nanomedicines, which feature unique
physicochemical properties and specific applicability, are extensively explored
for numerous oncological applications. Due to the well-defined morphology,
specific surface area, and pore volume, mesoporous silica nanoparticle (MSN)
based theranostic platforms have provided unprecedented opportunities for the
development of next-generation cancer nanomedicine. However, current
understanding on the underlying mechanisms of how these feasible theranostic
platforms interact with exogenous/endogenous triggers and how this unique
responsiveness for optimized cancer therapy can be taken advantage of is still
preliminary. In this progress report, efforts are made to give a comprehensive
overview of the development of MSN-based "smart" theranostic platforms, from
exogenous physical irradiation-triggered platforms for localized therapy to
endogenous biological stimulus-triggered platforms for tumor microenvironment
responsiveness. It is highly expected that these elaborately fabricated MSN-based
nanoformulations will play an indispensable role in the efficient cancer therapy
based on their high therapeutic outcome and reduced side effects.
PMID- 29938918
TI - Catalyst-Free Synthesis of Alkylpolyglycosides Induced by High-Frequency
Ultrasound.
AB - The irradiation of concentrated feeds of carbohydrates in alcoholic solution by
high-frequency ultrasound (550 kHz) induces the formation of alkylpolyglycosides
(APGs). This work is distinct from previous reports in that it does not involve
any (bio)catalyst or activating agent, it takes place at only 40 degrees C, thus
avoiding degradation of carbohydrates, and it selectively yields APGs with a
degree of polymerization in a window of 2-7, an important limitation of the
popular Fischer glycosylation. This ultrasound-based technology proved successful
with a range of different valuable carbohydrates and alkyl alcohols. The
elucidation of the structure of all the produced glycosides strongly suggests
that 1,6-anhydrosugars formed in situ are key intermediate species.
PMID- 29938919
TI - Mini Review of TiO2 -Based Multifunctional Nanocomposites for Near-Infrared Light
Responsive Phototherapy.
AB - Phototherapy with the properties of specific spatial/temporal selectivity and
minimal invasiveness has been acknowledged as one of the most promising cancer
therapy types. Among all the photoactive substance for phototherapy, titanium
dioxide (TiO2 ) nanomaterials are paid more and more attention due to their
outstanding photocatalytic properties, prominent biocompatibility, and excellent
chemical stability. However, the wide bandgap (3.0-3.2 eV) of TiO2 limits its
absorption only to the ultraviolet (UV) light region. For a long time, UV light
stimulated TiO2 was applied in the phototherapy researches of tumors located in
the skin layer, while it is unsatisfactory for most deep-tissue tumors. Due to
the maximum penetration into tissue existing in the near-infrared (NIR) region,
how to use NIR light to trigger photochemical reaction of TiO2 remains a big
challenge. In this review, two strategies to develop and construct NIR-triggered
TiO2 -based nanocomposites (NCs) for phototherapy are summarized, and the
relevant mechanism and background knowledge of TiO2 -based phototherapy are also
given in order to better understand the application value and current situation
of TiO2 in phototherapy. Finally, the challenges and research directions of TiO2
in the future clinic phototherapy application are also discussed.
PMID- 29938920
TI - Influence of agro-environmental pollutants on a biocontrol strain of Bacillus
velezensis.
AB - Metal- and pesticide-tolerant biocontrol agents are preferred in integrated pest
management, as such strains can be applied in combination with different
pesticides. The Bacillus velezensis strain SZMC 6161J proved to be sensitive to
copper, nickel, zinc, and cadmium, while manganese elevated its growth. At
concentrations higher than 1 mmol L-1 , zinc and iron inhibited the chymotrypsin
like activity of this strain. In addition, trypsin-like protease and palmitoyl
esterase activities were insensitive to all tested heavy metals in the applied
concentration range. We studied the effects of some widely used herbicides and
fungicides on the growth of this strain. The presence of sulfonylurea herbicides,
like bensulfuron-methyl, cinosulfuron, chlorsulfuron, ethoxysulfuron,
triasulfuron, and primisulfuron-methyl strongly inhibited the biomass production
of the strain even at the concentration of 6.25 mg L-1 . Glyphosate also
inhibited the growth above 30 mg L-1 . Similarly, contact fungicides like captan,
maneb, mancozeb, and thiram resulted in total inhibition at the concentration as
low as 6.25 mg L-1 . Interestingly, the sterol-biosynthesis-inhibiting fungicides
imazalil, fenarimol, penconazole, and tebuconazole also proved to be potent
inhibitors. Heavy metal- and fungicide-tolerant strains were isolated from the
parental strain and their antagonistic abilities were evaluated. There was no
substantial difference between the antagonism capability of wild-type strain and
the resistant mutants.
PMID- 29938921
TI - Prevalence and Characteristics of Persistent Clonal T Cell Large Granular
Lymphocyte Expansions in Rheumatoid Arthritis: A Comprehensive Analysis of 529
Patients.
AB - OBJECTIVE: Up to one-third of patients with T cell large granular lymphocyte (T
LGL) leukemia display symptoms of rheumatoid arthritis (RA). In Crohn's disease
and psoriasis, treatment with tumor necrosis factor (TNF) inhibitors is
associated with hepatosplenic gammadelta T cell lymphoma and with clonal
expansion of gammadelta T cells, respectively. This study was undertaken to
determine the prevalence of clonal T-LGL cells in patients with RA and define
risk factors for this rare hematologic malignancy. METHODS: A total of 529 RA
patients were recruited between November 2013 and August 2015. Eight-color flow
cytometry (fluorescence-activated cell sorting [FACS]) was performed to screen
for aberrant T cell populations of LGLs. Molecular analysis of the T cell
receptor was used to confirm the diagnosis in patients with suggestive FACS
findings. Electronic patient files were used to determine risk factors. Patients
with clonal populations were monitored prospectively for up to 4 years. RESULTS:
The median patient age was 61 years, and 74% were female. The median duration of
RA was 12 years. The median Disease Activity Score in 28 joints was 2.8, and
69.9% of patients had ever been treated with biologic disease-modifying
antirheumatic drugs. We identified clonal T-LGL expansions in 19 patients,
equaling a prevalence of 3.6%. The T-LGL cell clone was constant over time in
most patients and was significantly associated with the duration of the exposure
to TNF-blocking agents (P = 0.01). No other risk factors could be detected.
CONCLUSION: RA patients with long-term exposure to TNF-blocking agents were at a
greater risk of developing clonal expansions of LGLs. This finding may prompt
clinicians to refrain from using these substances in RA patients with known T
cell aberrations.
PMID- 29938922
TI - Eligibility for cardiac resynchronization therapy in patients hospitalized with
heart failure.
AB - AIMS: Recent guidelines recommend cardiac resynchronization therapy (CRT) in
mildly symptomatic heart failure (HF) but favour left bundle branch block (LBBB)
morphology in patients with moderate QRS prolongation (120-150 ms). We defined
how many patients hospitalized with HF fulfil these criteria. METHODS AND
RESULTS: A single-centre retrospective cohort study of 363 consecutive patients
hospitalized with HF (438 admissions) was performed. Electronic imaging,
electrocardiograms, and records were reviewed. Overall, 153 patients (42%) had
left ventricular ejection fraction (LVEF) <= 35%, and 34% of patients had QRS
prolongation. Eighty patients (22%) were potentially eligible with LVEF <= 35%
and QRS >= 120 ms or existing CRT. The majority (68 of 80) had a Class I or IIa
recommendation according to international guidelines (LBBB or non-LBBB QRS >= 150
ms or right ventricular pacing). Only a minority (12 of 80) had moderate QRS
prolongation of non-LBBB morphology. One-quarter (n = 22) of patients fulfilling
criteria were ineligible for reasons including dementia, co-morbidities, or
palliative care. A further eight patients required optimization of medical
therapy. CRT was therefore immediately indicated in 50 patients. Of these, 29
were implanted or had existing CRT systems. Twenty-one of the 80 patients
eligible for CRT were not identified or treated (6% of the total hospitalized
cohort). CONCLUSIONS: Twenty-two per cent of elderly real-life patients
hospitalized with HF fulfil LVEF and QRS criteria for CRT, most having a Class I
or IIa indication. However, a large proportion is ineligible owing to co
morbidities or requires medical optimization. Although uptake of CRT was
reasonable, there remain opportunities for improvement.
PMID- 29938923
TI - Subcellular localization and stability of MITF are modulated by the bHLH-Zip
domain.
AB - Microphthalmia-associated transcription factor (MITF) is a member of the basic
helix-loop-helix leucine zipper (bHLH-Zip) family and functions as the master
regulator of the melanocytic lineage. MITF-M is the predominant isoform expressed
in melanocytes and melanoma cells, and, unlike other MITF isoforms, it is
constitutively nuclear. Mutational analysis revealed three karyophilic signals in
the bHLH-Zip domain of MITF-M, spanning residues 197-206, 214-217, and 255-265.
Structural characterization of the MITF protein showed that basic residues within
these signals are exposed for interactions in the absence of DNA. Moreover, our
data indicate that neither DNA binding nor dimerization of MITF-M are required
for its nuclear localization. Finally, dimerization-deficient MITF-M mutants
exhibited a significantly reduced stability in melanoma cells when compared to
the wild-type protein. Taken together, we have shown that, in addition to its
well-established role in DNA binding and dimer formation, the bHLH-Zip domain of
MITF modulates the transcription factor's subcellular localization and stability.
PMID- 29938924
TI - Flexible-Device Injector with a Microflap Array for Subcutaneously Implanting
Flexible Medical Electronics.
AB - Implantable electronics in soft and flexible forms can reduce undesired outcomes
such as irritations and chronic damages to surrounding biological tissues due to
the improved mechanical compatibility with soft tissues. However, the same
mechanical flexibility also makes it difficult to insert such implants through
the skin because of reduced stiffness. In this paper, a flexible-device injector
that enables the subcutaneous implantation of flexible medical electronics is
reported. The injector consists of a customized blade at the tip and a microflap
array which holds the flexible implant while the injector penetrates through soft
tissues. The microflap array eliminates the need of additional materials such as
adhesives that require an extended period to release a flexible medical
electronic implant from an injector inside the skin. The mechanical properties of
the injection system during the insertion process are experimentally
characterized, and the injection of a flexible optical pulse sensor and
electrocardiogram sensor is successfully demonstrated in vivo in live pig animal
models to establish the practical feasibility of the concept.
PMID- 29938925
TI - Reduction of CD83 Expression on B Cells and the Genetic Basis for Rheumatoid
Arthritis: Comment on the Article by Thalayasingam et al.
PMID- 29938926
TI - "A waste of time without patients": The views of patient representatives
attending a workshop in evidence-based practice.
AB - BACKGROUND: Shared decision-making is a central element of evidence-based
practice (EBP). Training in EBP has traditionally focused on providers, but there
is an increasing interest in developing such educational resources for patients.
The aim of this study is to explore the views of patient representatives
attending a workshop in EBP. METHODS: We conducted three focus groups with
participants attending EBP workshops in 2013, 2014, and 2015. We used the
framework method for content analysis. We reviewed the transcribed interviews
independently and assigned initial codes and final categories to the
transcriptions. We created an analytical framework and a flow diagram to
visualize the category hierarchy and the relationship between categories.
RESULTS: We identified two main themes; "How to facilitate training in evidence
based practice for patients," and "Outputs of training in evidence based practice
for patients." Training in EBP for patient representatives "should reflect the
principles EBP," and include interaction with both health professionals and other
representatives. The educational needs of representatives are much the same as
those of health professionals, and the training should therefore be "on a par
with professionals." The relevance of such training may depend on the
representatives' mandate, and costs might be an important barrier. Important
outputs of such training include "becoming a knowledge manager," "enabling
participation and informed decisions" and "re-defining the patient
representatives' role." CONCLUSIONS: The findings of this study suggest that
training in EBP is attractive to patient representatives with outputs perceived
important. Organizers should consider the principles of EBP when planning such
training.
PMID- 29938927
TI - Developmental plasticity in reptiles: Critical evaluation of the evidence for
genetic and maternal effects on temperature-dependent sex determination.
AB - We critically review literature that examines variation in temperature-dependent
sex determination (TSD) within species. Although variation in sex ratio among
clutches of eggs from different females is common in reptiles with TSD, the
underlying mechanism that causes this variation is not clear. Authors have made
claims about genetic variation in TSD and maternal effects on TSD. The latter
type of study usually focuses on maternally derived steroids in egg yolk. Here,
we outline the types of experiments and data required to unequivocally
demonstrate that variation in sex ratio among clutches (1) has a genetic basis,
(2) is caused by maternally derived steroids, or (3) is influenced by both
factors. To date, few studies have met these requirements.
PMID- 29938928
TI - High prevalence of house dust mite sensitization in children with severe asthma
living at high altitude in a tropical country.
AB - BACKGROUND: Some studies, mainly in Europe, have shown a low level of
sensitization to house dust mite (HDM) allergens at high altitude (HA).
Differently, some others in tropical countries have shown a higher level. The aim
of this study was to evaluate allergens sensitization, including HDM, in children
with severe asthma (SA), residents at HA in a tropical middle-income developing
country. METHODS: Observational, analytical, cross-sectional study in children
aged 6-15 years old with SA at HA (2640 m). Skin prick tests (SPT), serum IgE,
exhaled fraction of nitric oxide (FENO ), spirometry, and asthma questionnaire
(ACT) were performed. Associations were explored by Pearson or Spearman
coefficients. RESULTS: We included 61 children. Most patients were male (61.3%),
median age: 10 years (Interquartile range [IQR]: 8-12), median BMI: 17 kg/m2
(IQR: 16-20); Median of positive SPT: 2 (IQR: 2-3). At least one SPT was positive
in 88.7% of patients and 87.9% were positive for at least one HDM. Serum IgE: 348
UI/mL (IQR: 154-760) and FENO : 22 ppb (IQR: 9-41). Prebronchodilator values were
(% predicted): FVC: 109.7% (+/-15.5%), FEV1 : 98.4% (+/-16.3); FEV1 /FVC: 82% (+/
8%). SPT were inversely correlated with the FEV1 /FVC (Rho: -0.34; 95% CI: -0.55
a -0.09; P = 0.008). CONCLUSIONS: These children with SA living at HA in a
tropical middle-income developing country have a high prevalence of HDM
sensitization. One explanation for this might be that tropical conditions, such
as temperature and humidity, could modify the effect of the altitude on asthma.
PMID- 29938929
TI - Thermal plasticity due to parental and early-life environments in the jacky
dragon (Amphibolurus muricatus).
AB - Developmental plasticity creates marked variation in individual phenotypes when
the environment is patchy, such as when the thermal environment varies.
Plasticity may occur in response to the environment experienced during an
individual's lifetime or to the environment experienced by parents
(transgenerational plasticity), and may be adaptive if it enhances fitness. In
particular, plasticity in thermal traits, such as preferred temperatures and
thermal limits, may improve performance and fitness based on temperatures in the
local environment. This study examined the influence of parental and offspring
thermal environments (duration of access to a basking lamp) on offspring thermal
traits (preferred temperatures and panting threshold) in jacky dragons (Agamidae:
Amphibolurus muricatus). Long-bask parental environments led, indirectly, to
higher preferred temperatures of offspring due to increased offspring body mass
compared to offspring of short-bask parents. The increase in median temperature
preference was associated with a higher voluntary minimum body temperature and a
narrower preference range, suggesting tradeoffs in thermal behavior and a
matching of offspring preferences to the parental environment. Parental thermal
treatment did not influence offspring panting threshold. Instead, the panting
threshold tended to be higher in offspring that were reared in the long-bask
treatment compared to those in the short-bask treatment, suggesting longer
basking environments increased thermal tolerance. Parental and offspring thermal
environment did not exhibit any interactive effect on thermal traits. The results
indicate that thermal environments experienced by lizards can have both
transgenerational and within-generation impacts on thermal traits, thus
influencing how populations respond to fluctuating or changing climates.
PMID- 29938930
TI - The effects of thermal stress on the early development of the lizard Anolis
sagrei.
AB - Across the globe terrestrial ectotherms-amphibians and non-avian reptiles-are
facing a range of emerging challenges. Increasing global temperatures, in
particular, are affecting all aspects of ectotherm biology and life history.
Embryonic development is a thermally sensitive period of the organismal
lifecycle, yet the impacts of thermal stress on the early development of
ectotherms have significantly lagged behind studies of later stages and adult
thermal physiology. Morphogenesis, the stage where the major anatomical systems
are actively forming, is particularly sensitive to thermal stress, yet is not
studied as often as later stages where growth is the primary process happening
within the egg. Here, we focus on the effects of thermal stress on the first 12
days of development, the stages of morphogenesis, in the lizard Anolis sagrei. We
examine the resiliency of the early developmental stages to heat stress by
incubating eggs at temperatures that parallel conditions observed today and
predicted over the next 50-100 years of projected climate change. Our results
suggest that some anole nests are currently at the thermal limits for which the
early embryonic stages can properly develop. Our results emphasize the importance
of studying early embryonic stages of development and the importance of studying
stage-specific effects of thermal stress on squamate development.
PMID- 29938931
TI - Urethral mobility and Point Aa of the Pelvic Organ Prolapse Quantification (POP
Q) system before and after midurethral sling operation.
AB - OBJECTIVE: The aim of the present study was to verify the usefulness of Point Aa
as a substitute marker of the Q-tip angle and urethral mobility before and after
midurethral sling operation for the treatment of stress urinary incontinence
(SUI) in women. METHODS: In this study, 118 women presenting with SUI who
underwent the tension-free vaginal tape obturator (TVTO) procedure were
prospectively examined and followed-up for >=6 months after operation. Spearman's
correlation coefficient was used to assess the degree of correlation between
Point Aa of the Pelvic Organ Prolapse Quantification system and Q-tip angles
before and after midurethral sling surgery. RESULTS: There were significant
postoperative changes in Point Aa (from -0.4 +/- 1.9 to -2.7 +/- 0.6; P = .001)
and Q-tip angle (from 58.7 +/- 19.4 to 15.4 +/- 17.5 degrees; P =.001) compared
with preoperative values. A fair correlation between Point Aa position and
straining Q-tip angle was found before (r = 0.45, P = .05) and after (r = 0.49, P
= .04) the procedure, with no significant difference in values before and after
the procedure (P = .62). CONCLUSIONS: The results of the present study show fair
correlation between the Point Aa position and straining Q-tip angle before and
after midurethral sling surgery. Point Aa could be used as an indicator of
urethral mobility after the TVTO procedure in women with SUI.
PMID- 29938932
TI - Modifiable cardiovascular risk factors in adolescents and adults with congenital
heart disease.
AB - OBJECTIVE: Individuals with congenital heart disease (CHD) may be at higher risk
of acquired cardiovascular disease than the general population due to their
underlying physiology and/or surgical sequelae. We sought to assess the
prevalence of cardiovascular disease risk factors in youth and adults with CHD.
METHODS: We assessed cardiovascular health as per the Cardiovascular Health in
Ambulatory Care Research Team (CANHEART) health index in patients with CHD aged
15+ years who attended cardiology outpatient clinics. Participants self-reported
smoking behavior, fruit and vegetable consumption, physical activity, and whether
they had diabetes and hypertension. Individual health indices were categorized
into ideal/not ideal, and sum of individual health indices was categorized as
poor, intermediate or ideal cardiovascular health as per CANHEART criteria.
RESULTS: We included n = 102 adults (35.4 +/- 12.9 years, 46% female) and n = 88
youth (17.2 +/-1.1 years, 41% female). Most individuals reported to be nonsmokers
(88% youth vs 86% adults) and to consume >=5 servings of fruit and vegetables per
day (83% vs 85%, respectively). More adults than youth were overweight/obese (52%
vs 22%, p < 0.001) though more adults than youth reported meeting age-specific
physical activity guidelines (84% vs 55%, p < 0.001). According to CANHEART
health index criteria, 32% of youth and 27% of adults were in ideal
cardiovascular health. CONCLUSIONS: A low proportion of individuals with CHD are
in ideal cardiovascular health, suggesting a need to promote healthy lifestyles
during adolescence and throughout adulthood in these individuals.
PMID- 29938933
TI - To beat, or not to beat, that is question! The spectrum of ciliopathies.
AB - Cilia are widely distributed throughout the human body, and have numerous roles
in physiology, development, and disease. Ciliary ultrastructure is complex,
consisting of nine parallel microtubules doublets, with or without motor dynein
arms and a central pair of microtubules. Classification of cilia has evolved over
time, and currently, four main classes are described: motile and non-motile cilia
with a "9 + 2" structure, and motile and non-motile cilia with a "9 + 0"
structure, which depend on the presence or absence of dynein arms and a central
pair. Ciliopathies are inherited multisystem disorders of cilia, and may present
with a varied spectrum of genotypes and phenotypes. Motor and sensory
ciliopathies were historically considered as distinct dysfunctions of motile and
non-motile cilia, but recent data indicate that the classical features of motor
and sensory cilia may overlap.
PMID- 29938934
TI - Stratification of Systemic Lupus Erythematosus Patients Into Three Groups of
Disease Activity Progression According to Longitudinal Gene Expression.
AB - OBJECTIVE: The highly heterogeneous clinical presentation of systemic lupus
erythematosus (SLE) is characterized by the unpredictable occurrence of disease
flares and organ damage. Attempts to stratify lupus patients have been limited to
classification based on clinical information, leading to unsuccessful clinical
trials and controversial research results. This study was undertaken to develop
and validate a robust method to stratify patients with lupus according to
longitudinal disease activity and whole-genome gene expression data in order to
establish subgroups of patients who share disease progression mechanisms.
METHODS: We used a cluster-based approach to stratify SLE patients based on the
correlation between disease activity scores and longitudinal gene expression
information. Clustering robustness was evaluated by the bootstrap method, and the
clusters were characterized in terms of clinical and functional features.
RESULTS: We observed a clear partition into 3 different disease clusters in 2
independent sets of patients, one pediatric and one adult, which was not
influenced by treatment, race, or other source of bias. Two of the clusters
differentiated into a group showing a correlation between the percentage of
neutrophils and disease activity progression and a group showing a correlation
between the percentage of lymphocytes and disease activity progression. The third
cluster, in which the percentage of neutrophils correlated to a lesser degree
with disease activity, was functionally more heterogeneous. Patients in the
neutrophil-driven clusters had an increased risk of developing proliferative
nephritis. CONCLUSION: Our findings indicate that SLE patients can be stratified
into 3 subgroups of patients who show different mechanisms of disease progression
and are clinically differentiated. Our results have important implications for
treatment options, the design of clinical trials, our understanding of the
etiology of the disease, and the prediction of severe glomerulonephritis.
PMID- 29938935
TI - Fibrin sealants in cardiac surgery: The last five years of their development and
application.
AB - This review article describes the use of fibrin glue or fibrin sealants and their
development over the past 5 years, with a focus on cardiac surgery. The roles of
various types of sealants that are available in hemostasis control are reviewed
briefly, together with the various potential risks and side effects of their use.
The results of experimental work reported during the last 5 years, clinical data
from the same period and the safety aspects of fibrin-based glues and sealants
are summarized, showing many advantages of their clinical application over the
use of synthetic glues or sealants that may be stronger in some cases, but less
safe. It can be concluded that the widespread use of fibrin sealants is fully
justified, as it benefits the patient as well as the surgeon through the improved
control of hemostasis without increasing any adverse effects or complications
during surgical procedures.
PMID- 29938936
TI - Genetic aspects of primary hyperaldosteronism.
AB - Primary hyperaldosteronism (PHA) is the most common form of secondary
hypertension of hormonal origin. It affects about 10% of all hypertensive
patients. It is connected with increased morbidity and mortality from
cardiovascular diseases (CVD) compared to patients with essential hypertension of
a similar age. Usually, it is an effect of bilateral adrenal hyperplasia (BAH) or
aldosterone-producing adenoma (APA), more rare causes of PHA are: unilateral
adrenal hyperplasia, aldosterone-producing adrenocortical carcinoma, ectopic
aldosterone-producing tumors and familial hyperaldosteronism. Recent genetic
studies have thrown a new light on the pathogenesis of PHA, classifying it as a
channelopathy. Several mutations within the ion channels encoding genes have been
identified. A possible link between primary hyperaldosteronism and polymorphism
of aldosterone synthase gene and ion channel genes is still being investigated.
In this manuscript, we focus on genetic aspects of primary hyperaldosteronism,
and present an up-to-date compilation of available data with the widened
pathogenetic approach.
PMID- 29938937
TI - Ovarian cancer stem cells: A target for oncological therapy.
AB - According to numerous studies, failures in treatment of ovarian cancer, i.e., a
relapse and metastases, result from a small population of cancer stem cells
(CSCs). They may also be responsible for tumor initiation. Cancer stem cells are
resistant to chemoand radiotherapy. Eradication of CSCs may involve the
application of salinomycin, metformin and Clostridium perfringens; the effect of
anti-angiogenic factors remains controversial. Salinomycin is an antibiotic
isolated from Streptomyces albus bacteria. Its CSC-eradicating effect has been
demonstrated both in ovarian cancer cell lines and in women with breast cancer.
Clostridium perfringens enterotoxin (CPE) has been demonstrated to destroy CSCs
in ovarian cancer both in vivo and in vitro. Metformin, apart from its
hypoglycemic effect, reduces the CSC population and inhibits the proliferation of
neoplastic cells and angiogenesis. Cancer stem cells with expression of VEGFR1+
have been described as affecting circulating cancer cells and influencing the
formation of metastases. Both positive and negative effects of anti-angiogenic
therapy on the CSC population have been documented.
PMID- 29938938
TI - [Prediction of seizures in sleep based on power spectrum].
AB - Seizures during sleep increase the probability of complication and sudden death.
Effective prediction of seizures in sleep allows doctors and patients to take
timely treatments to reduce the aforementioned probability. Most of the existing
methods make use of electroencephalogram (EEG) to predict seizures, which are not
specific developed for the sleep. However, EEG during sleep has its
characteristics compared with EEG during other states. Therefore, in order to
improve the sensitivity and reduce the false alarm rate, this paper utilized the
characteristics of EEG to predict seizures during sleep. We firstly constructed
the feature vector including the absolute power spectrum, the relative power
spectrum and the power spectrum ratio in different frequencies. Secondly, the
separation criterion and branch-and-bound method were applied to select features.
Finally, support vector machine classifier were trained, which is then employed
for online prediction. Compared with the existing method that do not consider the
characteristics of sleeping EEG (sensitivity 91.67%, false alarm rate 9.19%), the
proposed method was superior in terms of sensitivity (100%) and false alarm rate
(2.11%). This method can improve the existing epilepsy prediction methods and has
important clinical value.
PMID- 29938939
TI - [Effects of low frequency repetitive transcranial magnetic stimulation on
Electroencephalograph rhythm of children with autism].
AB - Autism spectrum disorders (ASD) is a complex developmental disorder characterized
by impairments in social communication and stereotyped behaviors.
Electroencephalograph (EEG), which can measure neurological changes associated
with cortical synaptic activity, has been proven to be a powerful tool for
detecting neurological disorders. The main goal of this study is to explore the
effects of repetitive transcranial magnetic stimulation (rTMS) on behavioral
response and EEG. We enrolled 32 autistic children, rTMS group ( n = 16) and
control group ( n = 16) and calculated the relative power of the delta, theta,
alpha, beta rhythms in each brain area by fast Fourier transform and Welch's
method. We also compared Autism Behavior Checklist (ABC) scores of the patients
before and after rTMS. The results showed a significant decrease in the relative
power of the delta band on right temporal region and parietal region and also a
decreased coherence on frontal region after rTMS intervention. The study proves
that rTMS could have positive effects on behavior of attention, execution
ability, and language ability of children and could reduce their stereotyped
behavior and radical behavior.
PMID- 29938940
TI - [Study on feature modulation of electroencephalogram induced by motor imagery
under multi-modal stimulation].
AB - Event-related desynchronization (ERD) is the basic feature of
electroencephalogram (EEG), and the brain-computer interface based on motor
imagery (MI-BCI) with the foundation of the analysis of ERD is of great
significance in motor function recovery. The valid ERD characteristics extracted
from EEG are the key to the performance of the BCI, so the study of which kind of
stimulation mode can prompt subjects to generate more obvious characteristics of
ERD is crucial. Four different stimulation modes are designed in this paper, and
the effects of motion imagery tasks under static text stimulation, grip video
stimulation, serial motion video stimulation of fingers as well as serial motion
video stimulation of fingers with sound on the characteristics of ERD are
analyzed. Combining the analysis of time-frequency spectrum, the power spectral
density curve, ERD value and brain topographic map, it is shown that the ERD
under serial motion video stimulation of fingers and serial motion video
stimulation of fingers with sound modes is much stronger and has wider range of
activation, and the BCI based on the analysis of ERD will have a better effect on
practical application. As a result, the recognition and acceptance of the users
of BCI system are improved in some extent.
PMID- 29938941
TI - [Research on the correlation of brain function based on improved phase locking
value].
AB - The phase lock value(PLV) is an effective method to analyze the phase
synchronization of the brain, which can effectively separate the phase components
of the electroencephalogram (EEG) signal and reflect the influence of the signal
intensity on the functional connectivity. However, the traditional locking
algorithm only analyzes the phase component of the signal, and can't effectively
analyze characteristics of EEG signal. In order to solve this problem, a new
algorithm named amplitude locking value (ALV) is proposed. Firstly, the improved
algorithm obtained intrinsic mode function using the empirical mode
decomposition, which was used as input for Hilbert transformation (HT). Then the
instantaneous amplitude was calculated and finally the ALV was calculated. On the
basis of ALV, the instantaneous amplitude of EEG signal can be measured between
electrodes. The data of 14 subjects under different cognitive tasks were
collected and analyzed for the coherence of the brain regions during the
arithmetic by the improved method. The results showed that there was a negative
correlation between the coherence and cognitive activity, and the central and
parietal areas were most sensitive. The quantitative analysis by the ALV method
could reflect the real biological information. Correlation analysis based on the
ALV provides a new method and idea for the research of synchronism, which offer a
foundation for further exploring the brain mode of thinking.
PMID- 29938942
TI - [A gradient-based direct aperture optimization].
AB - Aiming at the disadvantages of traditional direct aperture optimization (DAO)
method, such as slow convergence rate, prone to stagnation and weak global
searching ability, a gradient-based direct aperture optimization (GDAO) is
proposed. In this work, two different optimization methods are used to optimize
the shapes and the weights of the apertures. Firstly, in order to improve the
validity of the aperture shapes optimization of each search, the traditional
simulated annealing (SA) algorithm is improved, the gradient is introduced to the
algorithm. The shapes of the apertures are optimized by the gradient based SA
method. At the same time, the constraints between the leaves of multileaf
collimator (MLC) have been fully considered, the optimized aperture shapes are
meeting the requirements of clinical radiation therapy. After that, the weights
of the apertures are optimized by the limited-memory BFGS for bound-constrained
(L-BFGS-B) algorithm, which is simple in calculation, fast in convergence rate,
and suitable for solving large scale constrained optimization. Compared with the
traditional SA algorithm, the time cost of this program decreased by 15.90%; the
minimum dose for the planning target volume was improved by 0.29%, the highest
dose for the planning target volume was reduced by 0.45%; the highest dose for
the bladder and rectum, which are the organs at risk, decreased by 0.25% and
0.09%, respectively. The results of experiment show that the new algorithm can
produce highly efficient treatment planning a short time and can be used in
clinical practice.
PMID- 29938943
TI - [Medical computer-aided detection method based on deep learning].
AB - This paper performs a comprehensive study on the computer-aided detection for the
medical diagnosis with deep learning. Based on the region convolution neural
network and the prior knowledge of target, this algorithm uses the region
proposal network, the region of interest pooling strategy, introduces the multi
task loss function: classification loss, bounding box localization loss and
object rotation loss, and optimizes it by end-to-end. For medical image it
locates the target automatically, and provides the localization result for the
next stage task of segmentation. For the detection of left ventricular in
echocardiography, proposed additional landmarks such as mitral annulus,
endocardial pad and apical position, were used to estimate the left ventricular
posture effectively. In order to verify the robustness and effectiveness of the
algorithm, the experimental data of ultrasonic and nuclear magnetic resonance
images are selected. Experimental results show that the algorithm is fast,
accurate and effective.
PMID- 29938944
TI - [The acceleration algorithm for projection decomposition of dual-energy computed
tomography image reconstruction based on projection matching].
AB - Dual-energy computed tomography (CT) reconstruction imaging technology is an
important development direction in the field of CT imaging. The mainstream model
of dual-energy CT reconstruction algorithm is the basis material decomposition
model, and the projection decomposition is the crucial technique. The projection
decomposition algorithm based on projection matching was a general method. With
establishing the energy spectrum lookup table, we can obtain the stable solution
by the least squares matching method. But the computation cost will increase
dramatically when size of lookup table enlarges and it will slow down the
computer. In this paper, an acceleration algorithm based on projection matching
is proposed. The proposed algorithm makes use of linear equations and plane
equations to fit the lookup table data, so that the projection value of the
decomposition coefficients can be calculated quickly. As the result of simulation
experiment, the acceleration algorithm can greatly shorten the running time of
the program to get the stable and correct solution.
PMID- 29938945
TI - [Noninvasive numerical simulation of coronary fractional flow reserve based on
lattice Boltzmann method].
AB - In order to investigate the application of lattice Boltzmann method (LBM) in the
numerical simulation of computed tomography angiography-derived fractional flow
reserve (FFR CT), an idealized narrowed tube model and two coronary stenosis
arterymodels are studied. Based on the open source code library (Palabos), the
relative algorithm program in the development environment (Codeblocks) was
improved. Through comparing and analyzing the results of FFR CT which is
simulated by LBM and finite element analysis software ANSYS, and the feasibility
of the numerical simulation of FFR CT by LBM was verified . The results show that
the relative error between the results of LBM and finite element analysis
software ANSYS is about 1%, which vertifies the feasibility of simulating the
coronary FFR CT by LBM. The simulation of this study provides technical support
for developing future FFR CT application software, and lays the foundation for
the calculation of clinical FFR CT.
PMID- 29938946
TI - [Experimental study on the in vivo continuous measurement of pressure difference
between the anterior and the posterior chambers].
AB - A set of device for the in vivo measurement of the pressure difference between
the anterior and the posterior chambers (PDAP) was designed to investigate the
temporal varying rules of PDAP in the anterior segment of rabbit eyes. A platform
was established for the in vivo measurement of PDPA according to the mechanism of
joint implement. Rabbit models with high intraocular pressure (IOP) were
constructed by means of injecting Carbomer into anterior chamber to increase IOP.
The in vivo 24 hours continuous measurements of PDAP were performed for normal
rabbit eye and eye with high IOP. The developed device could sensitively response
to the small pressure difference in eye. The pressure difference in the normal
rabbit eye varied with time, and the variation range during a whole day was 5.84
96.84 Pa which reflected the existence of physiological rule. For the rabbit eye
with high IOP, pressure in anterior chamber was higher than that in posterior
chamber which was in consistence with the theory of self-adaptation adjustment.
The present study indicates that the approaches and device designed in this paper
can well implement the measurement of PDAP as well as the temporal varying rules
of PDAP in the anterior segment during a whole day.
PMID- 29938947
TI - [Non-leaching, broad-spectrum antibacterial poly (epsilon-caprolactone)/gelatin
QAS nanofiberous membranes for wound dressing].
AB - 5-20 wt% trimethoxysilylpropyl octadecyldimethyl ammonium chloride (QAS) was used
to modify Poly (epsilon-caprolactone) (PCL)-gelatin hybrid to fabricate non
leaching antibacterial nanofiber membranes (PG-Q) by electrospinning. The results
from scanning electron microscopy (SEM) and transmission electron microscopy
(TEM) indicated that the QAS leaded to phase separation between the QAS and PCL.
Hydrophilic test demonstrated that the PG-Q nanofiber membranes had hydrophobic
surface, which was help for peeling off the dressing from the wound.
Additionally, the physical and chemical cross-linking between the QAS/PCL and
QAS/gelatin were confirmed by Fourier transform infrared (FTIR), which were good
for long lasting antibacterial effect. The PG-Q membranes also showed excellent
cell-biocompatibility. Furthermore, compared with pure PCL nanofiber membrane,
the PG-Q nanofiber membranes, especially PG-Q15 (QAS: 15 wt%) and PG-Q20 (QAS: 20
wt%), showed a considerable increase in the bacteriostatic rate of S. aureus and
P. aeruginosa (more than 99% after 12 h). Therefore, electrospinning non-leaching
antibacterial nanofiber membranes could be an optimal choice for antibacterial
wound dressing.
PMID- 29938948
TI - [Preparation and properties of paclitaxel-loaded self-assembling nano-micelles of
cholesterol-bearing gamma-Polyglutamic acid].
AB - Paclitaxel (PTX)-loaded self-assembling nano-micelles (PTX/NMs) were prepared
based on amphiphilic cholesterol-bearing gamma-polyglutamic acid (gamma-PGA-graft
CH). The properties of PTX/NMs in vitro and in vivo were investigated. The
results indicated that PTX could be entrapped in gamma-PGA-graft-CH NMs. PTX/NMs
was characterized with a size of (343.5 +/- 7.3) nm, drug loading content of
26.9% +/- 0.8% and entrapment efficiency of 88.6% +/- 1.7% at the optimized
drug/carrier ratio of 1/10, and showed a pH-sensitive sustainable drug-release
and less cytotoxicity in vitro. In vivo release and the pharmacokinetics study in
mice showed that the elimination half-life ( t1/2 beta ) and area under curve
(AUC) of PTX/NMs were significantly higher than those of PTX/polyoxyethylene
castor oil (PTX/PCO), and less clearance (CL) of PTX/NMs was also observed.
PTX/NMs were distributed higher in liver and tumor than PTX/PCO, and showed a
good tumor-inhibiting activity in tumor-bearing mice. This study would lay a
foundation on the potential application of gamma-PGA-graft-CH NMs were the
antitumor drug-delivery.
PMID- 29938949
TI - [The preliminary study on biomechanical properties of four synthetic implants for
reconstructive surgery of pelvic floor dysfunction].
AB - This study aimed to investigate biomechanical properties of synthetic implants
for reconstructive surgery of pelvic floor dysfunction. In this dissertation, we
chose four synthetic implants, i.e. total pelvic floor repair system (PROLIFT),
gynecone TVT obtutator system (TVT-O), intra-vaginal sling placement device (IVS)
and acellular dermal matrix (Renov), for tensile test respectively. The
biomechanical properties of four synthetic implants were measured and analyzed
using a material testing machine (Instron 4302 versatile material testing
machine). The biomechanical parameters included ultimate stress strength, modulus
of elasticity, maximum load and maximum elongation. The results showed that the
maximum load of the four symthetic implants was TVT-O > IVS > PROLIFT > Renov,
and the maximum load of TVT-O was significantly higher than PROLIFT and Renov ( P
< 0.05). The ultimate stress strength was TVT-O > IVS > PROLIFT > Renov, with no
significant differences among them ( P > 0.05). The maximum elongation of the
four implants was TVT-O > PROLIFT > IVS > Renov, and the maximum elongation of
TVT-O and PROLIFT were both significantly higher than Renov ( P < 0.05). The
modulus of elasticity was IVS > Renov > TVT-O > PROLIFT, with no significant
differences among them ( P > 0.05). Taken together, the present study
demonstrates that the modulus of elasticity of IVS was the highest in the four
synthetic implants; TVT-O had the highest mechanical strength; The maximum load,
ultimate stress strength and maximum elongation of Renov were all the lowest; The
mechanical properties of PROLIFT was the most stable, and its modulus of
elasticity was the lowest in the four synthetic implants, which had good
extensibility and elasticity. Therefore, it is necessary to pay attention to the
biomechanical properties of new pelvic reconstructive materials for the clinical
pelvic reconstructive surgery.
PMID- 29938950
TI - [A multi-parameter resting-state functional magnetic resonance imaging study of
brain intrinsic activity in attention deficit hyperactivity disorder children].
AB - A great number of studies have demonstrated functional abnormalities in children
with attention-deficit/hyperactivity disorder (ADHD), although conflicting
results have also been reported. And few studies analyzed homotopic functional
connectivity between hemispheres. In this study, resting-state functional
magnetic resonance imaging (MRI) data were recorded from 45 medication-naive ADHD
children and 26 healthy controls. The regional homogeneity (ReHo), degree
centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) values were
compared between the two groups to depict the intrinsic brain activities. We
found that ADHD children exhibited significantly lower ReHo and DC values in the
right middle frontal gyrus and the two values correlated with each other;
moreover, lower VMHC values were found in the bilateral occipital lobes of ADHD
children, which was negatively related with anxiety scores of Conners' Parent
Rating Scale (CPRS-R) and positively related with completed categories of
Wisconsin Card Sorting Test (WCST). Our results might suggest that less
spontaneous neuronal activities of the right middle frontal gyrus and the
bilateral occipital lobes in ADHD children.
PMID- 29938951
TI - [A mechanical impedance-based measurement system for quantifying Parkinsonian
rigidity].
AB - At present the parkinsonian rigidity assessment depends on subjective judgment of
neurologists according to their experience. This study presents a parkinsonian
rigidity quantification system based on the electromechanical driving device and
mechanical impedance measurement method. The quantification system applies the
electromechanical driving device to perform the rigidity clinical assessment
tasks (flexion-extension movements) in Parkinson's disease (PD) patients, which
captures their motion and biomechanical information synchronously. Qualified
rigidity features were obtained through statistical analysis method such as least
squares parameter estimation. By comparing the judgments from both the
parkinsonian rigidity quantification system and neurologists, correlation
analysis was performed to find the optimal quantitative feature. Clinical
experiments showed that the mechanical impedance has the best correlation
(Pearson correlation coefficient r = 0.872, P < 0.001) with the clinical unified
Parkinson's disease rating scale (UPDRS) rigidity score. Results confirmed that
this measurement system is capable of quantifying parkinsonian rigidity with
advantages of simple operation and effective assessment. In addition, the
mechanical impedance can be adopted to help doctors to diagnose and monitor
parkinsonian rigidity objectively and accurately.
PMID- 29938952
TI - [A water maze for testing the motion of aquatic animal robots].
AB - The existing mazes are mainly used to study the learning and memory of animals.
However, there is still a lack of corresponding maze and method in the aspect of
the observation and test of aquatic animal robots. For this purpose, the authors
have developed a three-dimensional water maze combined with bilayer multi-channel
which equips with stratified lines and tick marks. This device is a rectangular
structure composed of one square bottom and four rectangular side walls, and the
channels of every side wall are composed of one upper channel and two lower
channels. The center of the upper channels is in the vertical center line of
every side wall, and the two uper channels of adjacent side walls are at 90
degrees degrees with each other, and the two lower channels of adjacent side
walls are at 45 degrees degrees with each other. There are stratified lines and
tick marks on the side wall to test the spatial location and movement
trajectories of aquatic animals. The carp robot was put into the water maze for
the underwater experimental detection. The success rates of left and right
steering at 135, 90 and 45 degrees as well as forward motion of the carp robots (
n = 10) were over 60%. This study showed that the device could be used to observe
and test the motion of the carp robot.
PMID- 29938953
TI - [A nucleus location method based on distance estimation].
AB - To locate the nuclei in hematoxylin-eosin (HE) stained section images more
simply, efficiently and accurately, a new method based on distance estimation is
proposed in this paper, which shows a new mind on locating the nuclei from a
clump image. Different from the mainstream methods, proposed method avoids the
operations of searching the combined singles. It can directly locate the nuclei
in a full image. Furthermore, when the distance estimation built on the matrix
sequence of distance rough estimating (MSDRE) is combined with the fact that a
center of a convex region must have the farthest distance to the boundary, it can
fix the positions of nuclei quickly and precisely. In addition, a high accuracy
and efficiency are achieved by this method in experiments, with the precision of
95.26% and efficiency of 1.54 second per thousand nuclei, which are better than
the mainstream methods in recognizing nucleus clump samples. Proposed method
increases the efficiency of nuclear location while maintaining the location's
accuracy. This can be helpful for the automatic analysis system of HE images by
improving the real-time performance and promoting the application of related
researches.
PMID- 29938954
TI - [Recognition of fatigue status of pilots based on deep contractive auto-encoding
network].
AB - We proposed a new deep learning model by analyzing electroencephalogram signals
to reduce the complexity of feature extraction and improve the accuracy of
recognition of fatigue status of pilots. For one thing, we applied wavelet packet
transform to decompose electroencephalogram signals of pilots to extract the
delta wave (0.4-3 Hz), theta wave (4-7 Hz), alpha wave (8-13 Hz) and beta wave
(14-30 Hz), and the combination of them was used as de-nosing
electroencephalogram signals. For another, we proposed a deep contractive auto
encoding network-Softmax model for identifying pilots' fatigue status. Its
recognition results were also compared with other models. The experimental
results showed that the proposed deep learning model had a nice recognition, and
the accuracy of recognition was up to 91.67%. Therefore, recognition of fatigue
status of pilots based on deep contractive auto-encoding network is of great
significance.
PMID- 29938955
TI - [Study on the center-driven multiple degrees of freedom upper limb rehabilitation
training robot].
AB - With the aging of the society, the number of stroke patients has been increasing
year by year. Compared with the traditional rehabilitation therapy, the
application of upper limb rehabilitation robot has higher efficiency and better
rehabilitation effect, and has become an important development direction in the
field of rehabilitation. In view of the current development status and the
deficiency of upper limb rehabilitation robot system, combined with the
development trend of all kinds of products of the upper limb rehabilitation
robot, this paper designed a center-driven upper limb rehabilitation training
robot for cable transmission which can help the patients complete 6 degrees of
freedom (3 are driven, 3 are underactuated) training. Combined the structure of
robot with more joints rehabilitation training, the paper choosed a cubic
polynomial trajectory planning method in the joint space planning to design two
trajectories of eating and lifting arm. According to the trajectory equation, the
movement trajectory of each joint of the robot was drawn in MATLAB. It laid a
foundation for scientific and effective rehabilitation training. Finally, the
experimental prototype is built, and the mechanical structure and design
trajectories are verified.
PMID- 29938956
TI - [Study on the inverse problem of electrical impedance tomography based on self
diagnosis regularization].
AB - The inverse problem of electrical impedance tomography (EIT) is seriously ill
posed, which restricts the clinical application of EIT. Regularization is an
important numerical method to improve the stability of the EIT inverse problem as
well as the resolution of the imaging. This paper proposes a self-diagnosis
regularization method based on Tikhonov regularization and diagonal weight
regularization method (DWRM). Firstly, the ill-posedness of the inverse problem
is analyzed by sensitivity. Then, the performance of the self-diagnosis
regularization is analyzed through the singular value theory. Finally, some
simulated experiments including simulations and flume experiment are carried out
and verify that the self-diagnosis regularization has better image quality and
anti-noise ability than those of traditional regularization methods. The self
diagnosis regularization method weakens the ill-posedness of inverse problem of
EIT and can prompt the practical application of EIT.
PMID- 29938957
TI - [Review of high-resolution peripheral quantitative computed tomography for the
assessment of bone microstructure and strength].
AB - Trabecular microstructure is an important factor in determining bone strength and
physiological function. Normal X-ray and computed tomography (CT) cannot
accurately reflect the microstructure of trabecular bone. High-resolution
peripheral quantitative computed tomography (HR-pQCT) is a new imaging technique
in recent years. It can qualitatively and quantitatively measure the three
dimensional microstructure and volume bone mineral density of trabecular bone in
vivo. It has high precision and relative low dose of radiation. This new imaging
tool is helpful for us to understand the trabecular microstructure more deeply.
The finite element analysis of HR-pQCT data can be used to predict the bone
strength accurately. We can assess the risk of osteoporosis and fracture with
three-dimensional reconstructed images and trabecular microstructure parameters.
In this review, we summarize the technical flow, data parameters and clinical
application of HR-pQCT in order to provide some reference for the popularization
and extensive application of HR-pQCT.
PMID- 29938958
TI - [Review of the research of spiking neuron network based on memristor].
AB - The rapid development of artificial intelligence put forward higher requirements
for the computational speed, resource consumption and the biological
interpretation of computational neuroscience. Spiking neuron networks can carry a
large amount of information, and realize the imitation of brain information
processing. However, its hardware is an important way to realize its powerful
computing ability, and it is also a challenging technical problem. The memristor
currently is the electronic devices that functions closest to the neuron synapse,
and able to respond to spike voltage in a highly similar spike timing dependent
plasticity (STDP) mechanism with a biological brain, and has become a research
hotspot to construct spiking neuron networks hardware circuit in recent years.
Through consulting the relevant literature at home and abroad, this paper has
made a thorough understanding and introduction to the research work of the
spiking neuron networks based on the memristor in recent years.
PMID- 29938959
TI - [A review of automatic liver tumor segmentation based on computed tomography].
AB - Liver cancer is a common type of malignant tumor in digestive system. At present,
computed tomography (CT) plays an important role in the diagnosis and treatment
of liver cancer. Segmentation of tumor lesions based on CT is thus critical in
clinical diagnosis and treatment. Due to the limitations of manual segmentation,
such as inefficiency and subjectivity, the automatic and accurate segmentation
based on advanced computational techniques is becoming more and more popular. In
this review, we summarize the research progress of automatic segmentation of
liver cancer lesions based on CT scans. By comparing and analyzing the results of
experiments, this review evaluate various methods objectively, so that
researchers in related fields can better understand the current research progress
of liver cancer segmentation based on CT scans.
PMID- 29938960
TI - [Research progress on artificial meniscus implants].
AB - Meniscus injury has been one of the most common knee injuries in current society.
The research on artificial meniscus implants as substitutes in meniscus
reconstruction therapy has become global focus in order to solve clinical
problems such as irreparable meniscus injury and symptoms after full or partial
meniscectomy. At present, researches on artificial meniscus implants mainly focus
on biodegradable meniscus scaffolds and non-biodegradable meniscus substitutes.
Although the commercialized meniscal implants, such as CMI (r), Actifit (r) and
NUsurface (r), have been applied in the clinical, none of them can perfectively
restore or permanently replace the natural meniscus tissue, effectively solve the
symptoms after meniscectomy, and prevent cartilage degenerative diseases. The
research progress, application, advantages and disadvantages of different kinds
of artificial meniscus implants are reviewed in this manuscript, and the prospect
is provided.
PMID- 29938961
TI - [Research progress on mechanical performance evaluation of artificial
intervertebral disc].
AB - The mechanical properties of artificial intervertebral disc (AID) are related to
long-term reliability of prosthesis. There are three testing methods involved in
the mechanical performance evaluation of AID based on different tools: the
testing method using mechanical simulator, in vitro specimen testing method and
finite element analysis method. In this study, the testing standard, testing
equipment and materials of AID were firstly introduced. Then, the present status
of AID static mechanical properties test (static axial compression, static axial
compression-shear), dynamic mechanical properties test (dynamic axial
compression, dynamic axial compression-shear), creep and stress relaxation test,
device pushout test, core pushout test, subsidence test, etc. were focused on.
The experimental techniques using in vitro specimen testing method and testing
results of available artificial discs were summarized. The experimental methods
and research status of finite element analysis were also summarized. Finally, the
research trends of AID mechanical performance evaluation were forecasted. The
simulator, load, dynamic cycle, motion mode, specimen and test standard would be
important research fields in the future.
PMID- 29938963
TI - Venezuelan Biomedical editors in crisis.
PMID- 29938962
TI - Identification of Nef-HIV-1 domains involved in p22-phox interaction and
superoxide production.
AB - Nef -HIV-1 has been shown to be involved in NADPH complex interaction and
superoxide production. The aim of this work was to study the domains involved in
the interaction between Nef and p22-phox. Two approaches were used: 1) in silico
modelling, to determine the potential binding motifs and design Nef truncated
forms and 2) functional assays. The results showed that GFPVT 68-72, FPDW 121-124
and REVLE 179-183 on Nef are critical for p22-phox (RPQIG 142-146 and PGGP 181
184) docking. However, only the region containing FPDW 121-124 on Nef is able to
induce superoxide production. Understanding the molecular mechanisms involved in
generating oxidative stress during HIV infection, is critical for therapeutic
intervention, in order to minimize viral replication and dissemination.
PMID- 29938964
TI - Association of the ELMO1 gene (snp rs1345365) with development of type 2 diabetes
mellitus in the Mexican mestizo population.
AB - The g.37190613 locus on 7p14.2-14.1 in the ELMO1 gene has a G>A polymorphism (SNP
rs1345365) that has been associated with diabetic nephropathy in different
populations. The genetic-association studies in type 2 diabetes mellitus (DM2) on
the Mexican population are limited. The aim of this study was to estimate whether
the polymorphism G>A of ELMO1 gene is associated with the development of DM2. We
included 148 DM2 individuals, 156 individuals with cardiovascular risk factors
without diabetes and 269 healthy proband without DM2. The polymorphism was
identified byPCR amplification specific allele (PASA), PAGE and silver staining.
The association was established by genetic epidemiological models; the dominant
model showed a positive association (p=0.0006) as a protective factor, and the
para-dominant model to heterozygous, as risk factor. In conclusion, this study
revealed the association of the SNP rs1345365 of the ELMO1 gene in a Mexican
population.
PMID- 29938965
TI - Biological effect of nutritional recovery on serum concentrations of inflammation
cytokines in the malnourished child.
AB - Children with severe malnutrition have a dysfunction of the immune response that
can significantly increase morbidity and mortality from infections. The aim of
this investigation was to evaluate the effect of nutritional recovery in serum
measurements of inflammatory cytokines; such as interleukin 12 (IL-12),
interleukin 17 (IL-17), interferon gamma (IFN-gamma) and tumor necrosis factor
alpha (TNF-alpha). In a prospective and longitudinal study, 24 severe
malnourished children aged between 1 and 2 years-old, who were part of a program
of nutritional recovery, were selected based on clinical and anthropometric
criteria. Serum measurements of cytokines were determined before and after
dietary treatment, using the technique of sandwich Enzyme-Linked ImmunoSorbent
Assay (ELISA). For comparisons, Student's t test was used, considered p <0.05 as
statistically significant. Adifference was observed in the concentrations of IL
12, IL-17, IFN-gamma and TNF-alpha before and after treatment (p <0.05), which
suggests that malnutrition provokes an inflammatory state and two months of
intensive nutritional support, not only promotes the clinical recovery of severe
malnourished children, but also the recovery of the immune response with regard
to the production of soluble mediators, such as cytokines.
PMID- 29938966
TI - Oral mucosal lesions in patients of Merida,Venezuela.
AB - There are very few epidemiological studies of oral mucosal lesions in Venezuela.
None of these studies has been conducted in the state of Merida. The aim of this
study was to determine the prevalence of oral mucosal lesions in a population
from Merida, Venezuela, describe their oral lesions' characteristics and analyze
the influence of parameters such as oral hygiene habits, harmful habits or
parafunctional habits. Of the 8640 patients seen in public and private dental
centers from Merida during one year, 120 (1.39%) had oral mucosal lesions. The
oral mucosal lesions most frequently found were: traumatic ulcers (17.5%),
recurrent herpes labialis (11.7%), denture stomatitis (10%), erythematous
candidiasis (10%) and recurrent aphthous stomatitis (9.2%). The main features of
these oral mucosal lesions were: more frequent in females and, main location on
the gingiva. Moreover, most of them were acute lesions (< 7 days), non-recurring
and painful lesions. Neither harmful habits nor parafunctional habits had
influence on the clinical features of the lesion.
PMID- 29938967
TI - Neuroprotective action of valproic acid accompanied of the modification on the
expression of Bcl-2 and activated caspase-3 in the brain of rats submitted to
ischemia/reperfusion.
AB - Valproic acid, apart from being known as an anti-epileptic drug, has been
proposedin the past few years, as a neuroprotective agent. The purpose of this
study was to investigatefirstly, if valproic acid protects the neurons from the
damage produced by oxidative stress inducedby ischemia-reperfusion in the brain
of healthy rats, under the transitory occlusion of the rightmiddle cerebral
artery. Secondly it was studied if this antiepileptic drug induces changes on
theexpression of Bcl-2 and activated caspase-3 as a possible mechanism of action
on apoptosis. Theneurological evaluation of the animals that were subject to
ischemia-reperfusion and receivedvalproic acid was better than the ones who
didn't receive it. On another subject, the levels ofmalondialdehyde on the right
cerebral hemisphere in the rats treated with valproic acid werebelow the levels
of the control group in the same hemisphere, whereas the amount of
carbonylatedproteins was reduced by 67% compared to the control group. Besides,
it was found by westernblot, that in homogenized brain tissue of the animals
under ischemia-reperfusion which receivedvalproic acid, there was a rise on the
density of the bands corresponding to Bcl-2, and a reductionof activated 3-capase
in comparison to the ones who were not treated with the antiepileptic drug.It's
concluded that the treatment with valproic acid prevented the neurological
deficit in healthyrats under Ischemia-reperfusion, blocking the effect of free
radicals on lipids and proteins ofthe affected brain cortex, and it is suggested
that the same drug intervenes on apoptosis inducedduring this type of damage,
being able to be a therapeutic alternative in the treatment of cerebralischemia.
PMID- 29938968
TI - Overweight-obesity and cardiometabolic risk factors in adolescents from Merida
city, Venezuela.
AB - To establish the prevalence of overweight-obesity and cardiometabolic risk
factors(CRF) (sedentary lifestyle, dyslipidemia, hypertension and impaired
carbohydrate metabolism) inchildren and adolescents in the city of Merida,
Venezuela, we studied 922 children and adolescentsfrom 9 to 18 years of age, from
different educational institutions. Anthropometric measurementsand arterial blood
pressure were recorded. Body mass index was calculated. Fasting blood
glucose,insulin and lipids levels, and glucose and insulin 2 h post-load glucose
were measured. HOMA-IRwas calculated. In order of frequency, sedentary lifestyle
was observed in 49.3% of participants,dyslipidemia in 28.3%, overweight-obesity
in 17.4% (7.9% obesity and 9.5% overweight), prehypertensionand hypertension
(PreHT/HT) in 8.8%, prediabetes in 4%, insulin resistance in 3.9%and metabolic
syndrome (MS) in 2.5%. CRF's were associated with overweight-obesity, beingthe
most common, dyslipidemia (50.3% vs 23.7% in normal weight) and PreHT/HT (23.8%
vs5.7%; p=0.0001 for both). The risk of PreHT/HT, dyslipidemia, and MS were 5.14,
3.26 and119.56 times more in overweight-obesity, than in low-normal weight
respectively (p=0.0001 forall). In conclusion, the frequency of overweight and
obesity in Merida has increased over time.Given its clear association with CRF,
it is recommended to provide the appropriated education toimprove nutritional
status.
PMID- 29938969
TI - Facial diplegia as unusual variant of Guillain-Barre syndrome: first case
reported in Venezuela.
AB - The Guillain-Barre syndrome (GBS) is the most common cause of acutegeneralized
paralysis. GBS is an acute inflammatory demyelinating polyradiculoneuropathy.
Itusually presents as a paralysis that starts in the lower limbs and then
progresses symmetricallyupward. The present study reports a case of bilateral
facial palsy as the initial manifestation ofGBS. This is a report of a case of a
37-year-old male, diabetic, that eight days after having sufferedacute sinusitis,
gradually presented with right hemicranial headache, dysarthria and
sialorrhea.The neurological examination disclosed the absence of the bilateral
frontal folds, accompaniedby epiphora, bilateral lagophthalmos, bilateral Bell
sign and salivary drooling through bothcommissures of lips. At 48 hours after
hospital admission the patient showed paresis in both upperlimbs. The
cerebrospinal fluid analysis reported 1.1cells/mm3, fully represented by
lymphocytesof normal aspect and total proteins were 196.9 mg/dL. The
electromyography was consistentwith acute demyelinating polyneuropathy, with a
predominant motor component and a majorfacial involvement. With the clinical and
laboratory findings, a diagnosis of GBS was established.Treatment was started
with plasmapheresis and intravenous immunoglobulin, with the
subsequentimprovement of the clinic. The facial diplegia is part of the regional
variants of GBS. Althoughabout 60% of GBS patients present with facial weakness,
it is usually preceded by weakness inthe limbs. This case makes evident that GBS
may present clinically as a facial diplegia.
PMID- 29938970
TI - ["We all have reason to envy you the rich experience you are having". Walter
Fritz Seemann's stay in Chicago as reflected in his correspondence with Alexander
Mitscherlich].
AB - "We all have reason to envy you the rich experience you are having". Walter-Fritz
Seemann's stay in Chicago as reflected in his correspondence with Alexander
Mitscherlich. W. F. Seemann was a "special student" at the Institute of
Psychoanalysis in Chicago from No-vember 1948 until June 1949 thanks to a
Fellowship from the Rockefeller Foundation, which had originally been granted to
his wife, Ursula Seemann-de Boor, who had been a poli-tical prisoner under the
Nazis. Based on a close reading of the correspondence between Seemann and
Alexander Mitscherlich the author outlines precisely the way in which
professional knowledge and experience were transmitted to post-war Germany, which
had been devastated by nationalsocialism and World War II. Seemann, as one of the
first non-emigrant Germans received into an analytic institute in the USA, was
given a surpri-singly friendly welcome. He profited from the rich libraries, the
cooperative style of the scientific community and some training analysis with
Fritz Moellenhoff, an immigrant from Berlin. Seemann conveyed his experience back
to Mitscherlich and post-war Ger-many by sending much-needed research literature
and by making contact with analysts who would agree to publish their work in the
newly founded Psyche. After his return to Germany Seemann became one of
Mitscherlich's closest colleagues in Heidelberg. However from 1954 onwards
Seemann stroke out on his own professionally.
PMID- 29938971
TI - ?
PMID- 29938973
TI - Coccidioidomycosis: current status of the endemic in Venezuela.
AB - Coccidioidomycosis is a systemic fungal infection endemic in the Americas, caused
by a dimorphic fungus. Inhalation of arthroconidia transported by wind colonize
lung tissue causing mycosis. Diagnosis is made through epidemiological and
mycological study, complemented by histopathological, molecular and immune
response. In Venezuela it has been reported since 1948 when Dr. Humberto Campins
described the first case in Barquisimeto, Lara state. The fungal diseases in
Venezuela are not mandatory notification,so that t6here is a serious
underreporting in the annual statistics of the country; however, the working
groups in Mycology manage to keep the data of the cases. The information provided
by bioclimatic and environmental variables in endemic areas can contribute to the
pursuit of ecological niches of the fungus in order to strengthen eco
epidemiological surveillance of clinical cases and research subclinical cases,
strengthening the preventive health system and appropriate medical management of
mycosis.
PMID- 29938974
TI - [Psychoanalysis in the service of a new social order].
AB - Max Horkheimer and Theodor W. Adorno, the proponents of a "critical theory of
society" exemplified an historical/ philosophical scepticism regarding the place
of the Subject in a capitalistic society, as well as towards the explanatory
value of Psychoanalysis. In spite of this they were very active in supporting the
reestablishment of Psychoanalysis in postwar Germany. These efforts were
evidenced in practice within the setting of the so called "reeducation"
programme, designed to overcome national-social attitudes in education and
culture. During their American exile both Horkheimer and Adorno worked
extensively with psychoanalysts. On the basis of this experience they organised
many lectures and congresses on Psy-choanalysis when they returned to Frankfurt.
This paper examines more closely their cooperation with Friedrich Hacker,
Alexander Mitscherlich, Heinrich Meng and Bruno Bettelheim.
PMID- 29938975
TI - Leptin's role in oral physiology and physiopathology.
AB - Leptin was characterized for the first time 20 years ago as an anorexigenic
peptidethat acts on the hypothalamus and has since been described as having a key
role in the functioningof a great number of tissues. The mouth is one of the
areas of the body where this peptide influencesprocesses, such as growth
induction and differentiation of various dental and periodontal
tissues,modulation of sweet tastes' perception in the taste buds, swallowing
regulation and immuneresponse activation. Moreover, leptin also plays an
important role in mediating the response todifferent oral aggressors, such as
periodontopathic bacteria and alcohol, as well as its involvementin certain types
of mouth cancer. This review aims to provide an overview of leptin's known
roleson the oral cavity to date, ranging from its function in a healthy mouth to
its involvement in oralphysiopathology.
PMID- 29938972
TI - Current aspects in sepsis approach. Turning things around.
AB - The incidence and prevalence of sepsis depend on the definitions and records that
we use and we may be underestimating their impact. Up to 60% of the cases come
from the community and in 30-60% we obtain microbiological information. Sometimes
its presentation is ambiguous and there may be a delay in its detection,
especially in the fragile population. Procalcitonin is the most validated
biomarker for bacterial sepsis and the one that best discriminates the non
infectious cause. Presepsin and pro-adrenomedullin are useful for early
diagnosis, risk stratification and prognosis in septic patients. The combination
of biomarkers is even more useful to clarify an infectious cause than any
isolated biomarker. Resuscitation with artificial colloids has worse results than
crystalloids, especially in patients with renal insufficiency. The combination of
saline solution and balanced crystalloids is associated with a better prognosis.
Albumin is only recommended in patients who require a large volume of fluids. The
modern molecular methods on the direct sample or the identification by MALDI-TOF
on positive blood culture have helped to shorten the response times in diagnosis,
to optimize the antibiotic treatment and to facilitate stewardship programs. The
hemodynamic response in neonates and children is different from that in adults.
In neonatal sepsis, persistent pulmonary hypertension leads to an increase in
right ventricular afterload and heart failure with hepatomegaly. Hypotension,
poor cardiac output with elevated systemic vascular resistance (cold shock) is
often a terminal sign in septic shock. Developing ultra-fast Point-of-Care tests
(less than 30 minutes), implementing technologies based on omics, big data or
massive sequencing or restoring "healthy" microbiomes in critical patients after
treatment are the main focuses of research in sepsis. The main benefits of
establishing a sepsis code are to decrease the time to achieve diagnosis and
treatment, improve organization, unify criteria, promote teamwork to achieve
common goals, increase participation, motivation and satisfaction among team
members, and reduce costs.
PMID- 29938976
TI - Overwiew of the Coagulation System and laboratory tests for its study.
AB - In the sixties, the clotting cascade was proposed, which describes thecoagulation
process as a sequence of enzymatic events initiated by two different pathways,the
intrinsic and the extrinsic pathways, converging on a common pathway, to generate
amultifunctional enzyme, thrombin, whose main function is to convert fibrinogen
into fibrin,a protein that polymerizes spontaneously to form the building block
of a hemostatic clot.Later, it was proposed a cell-based model of the hemostasis
according to that coagulationdoes not occur as a consequence of linear sequential
enzyme activation pathways, but rathervia a network of simultaneous interactions
between plasmatic and transmembrane proteins,as well as several cellular types,
that allow the formation of highly efficient enzymaticcomplexes that lead to
thrombin generation. In this review, we summarize these twoapproaches
highlighting the functions of thrombin within the hemostasis and the
inhibitionmechanisms that regulate the blood coagulation. Moreover, we described
different teststhat are used to assess the function of the coagulation system,
such as: activated partialthromboplastin time, prothrombin time, thrombin time,
reptilase time, ecarin clotting time,and the use of chromogenic substrates to
evaluate individual coagulation factors. Finally,because of thrombin generation
is a fundamental part of the blood coagulation and, anestimation of how well a
particular individual can generate thrombin may correlate witheither a risk of
bleeding or thrombosis, we also include the existing methods to evaluate
thepotential of thrombin generation in an individual.
PMID- 29938978
TI - Considerations on reviewers and authors from papers received for publication in
Investigacion Clinica.
PMID- 29938979
TI - ["It would also be cowardly to leave the field here to the enemies of
Psychoanalysis." The correspondence between Richard and Edith Sterba and Anna
Freud 1946-1962].
AB - This artic-le describes the fate of the Viennese psychoanalysts Richard and Edith
Sterba after their emigration to the United States. The author examines the
correspondence between the Sterbas and Anna Freud which is to be found amongst
the Anna Freud papers in the Lib-rary of Congress in Washington. The letters
illustrate Richard Sterbas ardent admiration for both Sigmund and Anna Freud. The
Sterbas tried to persuade Anna Freud to move to the United States permanently.
The correspondence also gives insights into very per-sonal views of both the
Sterbas and Anna Freud about colleagues and historical events. The paper in
addition depicts the events which eventually led to the dissolution of the
Detroit Psychoanalytic Society and demonstrates how the Sterbas thereby lost
important professional positions. When psychoanalytic training was resumed in
Detroit the Sterbas were ignored both as teachers and as training analysts.
PMID- 29938977
TI - ["Dear Max, how much we are one, I was only clearly aware the day after leaving
my last letter to you." Max Horkheimer and Karl Landauer as the first
psychoanalyst at the Frank-furt Institute for Social Research].
AB - The Frankfurt School is known to be the first institution in Germany that in 1929
has officially related psychoanalysis to a university. The most important person
in this process was Karl Landauer. With him Fromm, Horkheimer and others
completed their training analyzes, he decisively worked in the Institute and the
first volumes of the Journal of Social Research. Landauer and Horkheimer
regularly ex-change information in the time of emigration and discuss their texts
together. Landauer is also responsible for the reception of psychoanalysis in
Horkheimer's further programs he writes for the Institute, as in his programmatic
essay "Egoism and freedom-movement" from 1936. When he was murdered in
concentration camp in 1945, it was a great per-sonal and theoretical loss for
Horkheimer which he hardly could overcome. Also the known dispute between Adorno
and Fromm at the Institute for Social Research has as a backbone an old rivalry
between the psychoanalytic institutes from Berlin and Frankfurt, which is
exacerbated during the emigration and the Gleichschaltung in fascist Germany.
PMID- 29938980
TI - Antimicrobial efficacy of orthodontic primer added with silver nanoparticles.
Cross-sectional in vitro study.
AB - The antimicrobial efficacy of the silver nanoparticles (NPsAg), incorporated into
the adhesive (primer) placed in the enamel adjacent to fixed orthodontic
appliances (brackets), was evaluated. An experimental study was performed on 40
premolars in vitro, which were divided into two groups with brackets, one
cemented with conventional primer and another added with NPsAg, placed in culture
media previously inoculated with Streptococcus mutans, and sampled for culturing
and counting colony forming units (UFC) on days 1, 15 and 30. A decrease in the
presence of Streptococcus mutans in the samples after 15 days with nanoparticle
aggregation was observed, and a reduction in the effect of said nanoparticles
after 30 days. This reduction of the nanoparticles effects can be due to the
absence of mechanical cleaning, which favored the bacterial aggregation on the
biofilm, affecting its antimicrobial effect. This suggest the need for realizing
studies in "vivo" which will allow the observation of the behavior of the
biometals on the buccal medium. The NPsAg added to the primer are an effective
tool to prevent the demineralization of the enamel around the fixed orthodontic
appliances.
PMID- 29938981
TI - BRCA1 expression in benign and malignant breast lesions.
AB - The majority of breast cancers are sporadic cancers; however, there is an
estima!ted proportion of 5% to 10%, where a hereditary predisposition appears,
mainly associated with germline mutations in the BRCA1 and BRCA2 genes. Such
mutations increase the predis-position to develop the disease during the course
of life. The overall objective of this work was to evaluate the expression of the
BRCA1 gene by immunohistochemistry (IHC). The study was conducted in women
diagnosed with benign lesions or invasive breast ductal carcinoma in follow-up
care at the Institute of Oncology "Dr. Miguel Perez Carreno" in Valencia,
Venezuela. Expression of the BRCA1 protein was analyzed and the results were
compared with the benign lesions classification given by DuPont and Page and the
intrinsic molecular subtypes defined by IHC. From this analysis it was found that
in both, non-infiltrative lesions (proliferative and carcinoma in situ), as well
as in infiltrating carcinomas, predominated the cases with BRCA1 nuclear labeling
by IHC (<=10 %). Furthermore, the relationship of expression of BRCA1 with the
average overall survival, showed a poor prognostic value obtained when the
nuclear and cytoplasmic expression of BRCA1 was <=10%, with p<0.05. Finally,
based on the results, it is suggested that the assessment of BRCA1 expression by
IHC should be included in the approach algorithm of women at risk of developing
breast cancer.
PMID- 29938982
TI - [Biographical discoveries and supplements around the 3rd psychoanalytic congress
in Weimar 1911, Part II: Maria von Stach, Georg Wanke ? and the photographer
Franz Valtl].
AB - In the first section of this paper Andreas Peglau presents new material on the
vicissitudes of the life of publicist and feminist Maria v. Stach. Of particular
interest is her longtime relationship to Karen Horney, both as patient and as
friend. ? Michael Schroter adds new information about Georg Wanke, director of a
sanatorium in Thuringia, who came to psychoanalysis from hypnotism. In
September/October 1911 he (1) visited the Weimar Congress, (2) presented a paper
on psychoanalysis to his psychiatric colleagues, and (3) joined the Berlin
Psychoanalytic Association. His 1924 book contains some remarkable ideas on
euthanasia which seem to have been directly approved by Freud. - Last but not
least A. Peglau provides a portrait of the man who created the Weimar photo,
Franz Valtl.
PMID- 29938984
TI - ?
PMID- 29938983
TI - Miocarditis inducida por clozapina durante la evaluacion observacional,
transversal y ongitudinal: comparacion con otros antipsicoticos en ambientes
naturalisticos.
AB - Myocarditis occurs more frequently during clozapine (CLZ) administration than
during treatment with other antipsychotic drugs (APs). In this observational
study, we transversally screened outpatients for myocarditis by comparing a CLZ
group of 132 subjects, with a non-CLZ group taking other APs (n = 371) only, and
in 21 CLZ-treated patients and 18 subjects treated with other APs who had been
followed for more than one year. The protocol included a) assessment of symptoms
such as dyspnea, tachycardia, chest discomfort, fever, cough, and edema, b) blood
pressure and heart auscultation; c) a standard electrocardiogram after a 5-minute
rest, d) white cell count, and qualitative determination of troponin I, creatine
kinase-MB and myoglobin, and e) a cardiologist evaluation of subjects with
suspected myocarditis. Only one case of myocarditis was detected, providing an
approximation of the frequency of myocarditis of 1.6% in the first month of
treatment. This was a 30-year-old man with schizophrenia who developed symptoms
at day 6 after starting a treatment with 200 mg of CLZ a day without titration.
Myocarditis was not observed during prolonged CLZ or other AP administration.
These results support the proposal of starting CLZ treatment with a low dose and
the feasibility of a simple protocol for myocarditis detection in psychiatry
primary care.
PMID- 29938985
TI - High prevalence and poor control of hypertension in five venezuelan populations:
the VEMSOLS study.
AB - The prevalence of hypertension in multiple regions of Venezuela is unknown. The
objective of this study was to estimate the prevalence of hypertension in five
populations from three regions. During 2006 to 2010, 1392 subjects aged 20 or
older were selected by multistage stratified random sampling from all households
in five municipalities from: Lara State (Western region), Merida State (Andean
region), and Capital District (Capital region). Anthropometric measurements,
blood pressure, and biochemical analysis were obtained from each participant.
Mean age was 45.2 +/- 0.4 years and 68% were females. The overall prevalence of
hypertension was 31.3% (CI 95% 28.9 - 33.8), it was higher in men than women
(38.1% [33.5 - 42.8] vs. 28.2% [25.4 - 31.2], respectively; p <0.001). The
hypertensive participants were older, with higher body mass index (BMI), glucose,
total cholesterol, LDL-c, and triglycerides; and lower values of HDL-c, than pre
hypertensive and normotensive participants (p < 0.05). In women, hypertension
prevalence increased linearly for every decade of life and by category of BMI;
whereas in men it increased until the fifth decade of life, and was similar in
patients with overweight and obesity. The risk of hypertension increased with
age, the presence of obesity, diabetes, overweight and family history of
hypertension. Only 17.7% of the hypertensive subjects were both treated and
controlled. In conclusion, about one third of the subjects evaluated had
hypertension and about one fifth of them had their hypertension under control. In
Venezuela, hypertension is a serious public health problem exacerbated by age and
overweight.
PMID- 29938986
TI - ?
PMID- 29938987
TI - Detection of F8 mutations in carriers and patients with severe hemophilia A.
Identification of a novel mutation.
AB - The molecular diagnosis of haemophilia A (HA) patients has many benefits
including diagnosis confirmation and inhibitor risk development prediction. In
female carries of a mutation, the molecular diagnosis allows for genetic
counseling and prenatal diagnosis, which have become part of the comprehensive
care for HA in many countries. Therefore, the aim of this study was to determine
the F8 mutations in severe HA (sHA) patients and female carriers. In 12 patients
with sHA, the presence of the intron 22 and intron 1 inversions was investigated
using an inverse and a conventional PCR method, respectively. In patients
negative for the inversions, the F8 gene was screened through conformation
sensitive gel electrophoresis (CSGE) and further sequencing. The causative
mutation was successfully identified in 6/12 patients, including the novel
mutation p.G190C. The mothers of these six patients and those of seven other sHA
patients molecularly diagnosed in a previous work were investigated for the
presence of the genetic alterations found in their sons. All mothers were found
to be carriers. This is the first study conducted in Venezuela which directly
analyzes the F8 gene in potential carrier mothers to specifically identify the
presence of the mutation that was detected in their sons, and complements a
previous study on sHA patients. Our findings will facilitate the implementation
of regular screening of HA carriers in our country and will allow a better care
of bleeding symptoms and genetic counseling.
PMID- 29938988
TI - PAGOD syndrome and vascular anomalies: is a defect embryonic angiogenesis? A case
report and review.
AB - PAGOD Syndrome is an acronym for lung and pulmonary arteries hypoplasia,
agonadism, omphalocele / diaphragmatic defect and dextrocardia. A series of 21
patients is described, where 90.5% had a 46,XY karyotype and only two cases
46,XX; 66.6% exhibited a female phenotype and 28.6% ambiguous genitalia. The
occurrence of two patients 46,XX excludes the Y chromosome as a carrier of the
genetic defect and raises the possibility of a recessive X-linked inheritance,
without ruling out that the observed cases in siblings may be due to mutations in
other genes as Stra6, VEGFA, VEGFB, VEGFC, and alternative splicing of
transcripts VEGFA, HIF1, HIF2, among others. Congenital malformations were
observed in patients' genitals and gonads 85.7%, 66.6% in diaphragm and abdominal
wall , heart 80.9%, 71.4% lungs, blood vessels 80.9% and 42.8% in abdomen. The
review of patients has demonstrated a high degree of variability in the
expression of malformations of organs and organ systems. Vascular malformations
represent an important and characteristic component of PAGOD syndrome and whose
base morphogenetic syndrome may be due to a defect in early embryonic
angiogenesis with impact on organogenesis and system development. Among genes
related to vascular remodeling during embryogenesis, tissue regeneration and
carcinogenesis, the Endothelial Growth Factor D Vascular (VEGFD), located in the
Xp22.31 region, with expression in lung, heart, small intestine, uterus, breast,
neuroblastoma and neural tissue, represents a strong candidate for molecular
analysis as a cause of the syndrome.
PMID- 29938989
TI - Molecular identification of multidrug resistant Enterobacter hormaechei in
Venezuela.
AB - Besides the importance of Enterobacter cloacae species complex as a nosocomial
pathogen, little is known about the frequency of each species/genotype. Here, we
describe a strain of E. hormaechei subsp. hormaechei isolated from a bronchial
secretion of a patient, in the Intensive Care Unit at the General Hospital of
Cumana, Venezuela, who died due to complications of his infection. The molecular
identification was done by sequencing the 16S rRNA gene and comparing it to
sequences from the GenBank. This strain showed resistance to multiple families of
antibiotics (MDR), and the genes blaKPC and blaVIM were detected by PCR. This is
the first time E. hormaechei has been identified in Venezuela.
PMID- 29938990
TI - Psychotherapists: Should we meet Arthur Schopenhauer?.
AB - Arthur Schopenhauer (1788-1860) is known as the pessimist philosopherand the
psychologist of the will. He anticipated some features of cognitive neuroscience,
psychoanalysisand evolutionary psychology, but he is relatively unfamiliar to
most contemporarymental health professionals. Schopenhauer conceived the will as
the universe's essence; purposefulhuman actions are a small part of it. We do not
directly perceive the will, but only itsphenomena through the 'Veil of Maya',
which, in contemporary terms, refers to the cognitiveand perceptual limits
imposed by our own biological species. This is why Schopenhauer positsthat we
have a representation (idea) of the world. We have a direct access to the will by
perceivingour body's desires. The will is insatiable and selfish. Because of
these will's features,there is no possibility of collective or global salvation.
However, individual or existential salvationmay occur by denying the will through
a path that includes: 1) an aesthetic experienceparticularly with the aid of art,
that allows contemplation of the 'Platonic Ideas', lesseningdesire and promoting
knowledge through contemplation,; 2) the ethical experience refers tothe insight
about the unity of the universe, particularly by realizing the ubiquity of
sufferingand neediness, and 3) the metaphysical step which promotes compassion
and asceticism. Thesephilosophical principles may add to specific
psychotherapeutic techniques in expanding theindividual's awareness beyond
herself/himself, and thus arise and improve the psychologicaloutcome.
PMID- 29938991
TI - Oropouche Virus: what is it and how it is transmitted?
PMID- 29938992
TI - From the editors: bringing the Joslin Clinical Guidelines to the diabetes care
community.
PMID- 29938993
TI - Joslin Diabetes Center Clinical Oversight Committee.
PMID- 29938994
TI - CHAPTER 1. Clinical guideline for adults with diabetes.
PMID- 29938995
TI - CHAPTER 2. Clinical nutrition guideline for overweight and obese adults with type
2 diabetes (T2D) or prediabetes, or those at high risk for developing T2D.
PMID- 29938996
TI - CHAPTER 3. Guideline for detection and management of diabetes in pregnancy.
PMID- 29938997
TI - CHAPTER 4. Guideline for the care of the older adult with diabetes.
PMID- 29938998
TI - CHAPTER 5. Clinical guideline for pharmacological management of adults with type
2 diabetes.
PMID- 29938999
TI - Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolated from
patients in two public hospitals in Carabobo and Zulia states, Venezuela.
AB - Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria (K. pneumonia
carbapenemase) are the most important causative agents of nosocomial infections
worldwide. These isolates have been identified in Venezuela, but little is known
about their local spread. The aim of this study was to perform molecular
epidemiology of KPC-producing K. pneumoniae isolated from two public hospitals in
the Carabobo and Zulia states of Venezuela. Thirty-two K. pneumoniaei solates,
phenotypically classified as KPC producers were subjected to PCR to detect the
presence of blaKPC genes and their location within transposon Tn4401, and the
blaKPC product was sequenced to identify the KPC allele. Genotypic analysis was
performed using repeated extragenic palindromic PCR (rep-PCR) and Multi Locus
Sequence Typing (MLST). Finally, a conjugation assay determined whether the
blaKPC genes were carried on transferable plasmids. The results indicate that the
32 isolates contained the blaKPC-2 variant associated with isoform Tn4401b, and
were distributed in nine sequence types (ST), one of which was new. Conjugation
assays indicate that 87.5% of the isolates contain the gene blaKPC on mobilizable
plasmids. In these hospitals, the blaKPC-2 gene is spreading through the plasmids
carrying the transposon Tn4401b. The most common ST belongs to Clonal Complexes
CC258 and CC147, which play an important role in the dispersion of resistance
tocarbapenems worldwide.
PMID- 29939000
TI - Inotropic and chronotropic effects of propranolol in isolated atrium of rats with
fructose-induced insulin-resistance
AB - Insulin resistance (IR) is a metabolic deficiency associated with type 2 diabetes
and commonly related to the pathogenesis of cardiovascular diseases, being the
determining factor of the metabolic syndrome. This research aims to understand
the chronotropic and inotropic effects of Propranolol in isolated atrium of rats
with fructose-induced insulin-resistance. For this reason, 16 male Sprague-Dawley
rats were assigned to two groups and given ad libitum access to one of the
following diets: Perrarina(r) dog chow or Perrarina(r) dog chow supplemented with
vegetable shortening and with fructose (20%) and sucrose (20%) added to the water
supply. Both groups were maintained on their respective dietary regimens for
eight months. Atthe end of this period insulin resistance was verified by routine
blood test. The rat hearts were rapidly removed, and the atria were dissected and
kept in Krebs solutions (37oC, pH 7.4; 95% O2 - 5% CO2) in an isolated organ bath
Letica(r), connected to a polygraph Grass(r), registering atria frequency. The
Student's t-test was used to evaluate statistical differences between the two
groups (p<0.05). Cumulative dose-response curves with isoproterenol were
established in basal condition, and after fifteen minutes of pre-incubation with
propranolol (1x10-6 M). A significant positive chronotropic effect was observed
in IR rats (68.92+/-4.16 vs 44.92+/-4.08 beats/sec of control; p<0.001). The
maximum force of atrial contraction after pre-incubation with propranolol was
significantly higher in the IR group (91.67+/-2.10 vs 42.6 +/- 3.5; p<0.001).
These findings suggest that a blunted response of atrial beta-adrenoceptor to
propranolol exists in rats with fructose- induced insulin-resistance.
PMID- 29939001
TI - Prehipertension: influence of psychological stress in adolescents.
AB - The article examines the association between psychological stress (PS)
andprehypertension (PH) in 690 adolescents, 260 males and 430 females, whose
average age was15.2 years (SD = 1.5). Their blood pressure (BP) was measured on
separate days at school, bythe oscillometric method (Dinamap) in a seating
position. All of them completed a survey assessinglife events and social
readjustment (both scales associated with life stressors in
adolescence).Participants were classified according to BP levels in
prehypertensive (PH) and normotensive(N). The presence of PS was evaluated as
severe stressful life events. The Chi-square testwas used to study the
association between PS and the presence of PH. The results showed thepresence of
PH in 9.2% (n = 24) in males and 3.5% (n = 15) in females, while the presence
ofPS ocurred in 70 males (26.9%) and 155 females (36.0%).When applied to the
whole data, theChi-square statistical test showed no association between PS and
the condition of prehypertension[PH with PS = 15 vs. N with PS = 24, (P= 0.42)].
However, when subjects were classifiedby gender, there was a significant
association between PS and PH in female adolescents [PHwith PS = 9 vs N with PS =
6 (P = 0.04)]. This result suggests that, at early ages, female adolescentsmay be
more vulnerable than males to PS as a determining factor to the condition of PH.
PMID- 29939002
TI - Fabricating 3D Macroscopic Graphene-Based Architectures with Outstanding
Flexibility by the Novel Liquid Drop/Colloid Flocculation Approach for Energy
Storage Applications.
AB - Inspired by "water ripples" in nature and the flocculation phenomenon in colloid
chemistry, a novel liquid drop/colloid flocculation approach is developed to
fabricate an extremely flexible and compressible 3D macroscopic graphene-based
architecture (hydrogels or aerogels), via a new coagulation-induced self-assembly
mechanism. This facile and universal technique can be achieved in a neutral,
acidic, or basic coagulation bath, producing microsized hydrogels with various
structures, such as mushroom, circle, disc shapes, etc. The method also allows us
to introduce various guest materials in the graphene matrix using transition
metal salts as the coagulating bath. A mushroom-shaped NiCo oxide/GS hybrid
aerogel (diameter: 3 mm) is prepared as an example, with ultrathin NiCo oxide
nanosheets in situ grown onto the surface of graphene. By employing as binder
free electrodes, these hybrid aerogels exhibit a specific capacitance of 858.3 F
g-1 at 2 A g-1, as well as a good rate capability and cyclic stability. The
asymmetric supercapacitor, assembling with the hybrid aerogels as cathode and
graphene hydrogels as anode materials, could deliver an energy density of 21 Wh
kg-1 at power density of 4500 W kg-1. The ease of synthesis and the feasibility
of obtaining highly flexible aerogels with varied morphologies and compositions
make this method a promising one for use in the field of biotechnology,
electrochemistry, flexible electronics, and environment applications.
PMID- 29939004
TI - Emerging Biomimetic Applications of DNA Nanotechnology.
AB - Re-engineering cellular components and biological processes has received great
interest and promised compelling advantages in applications ranging from basic
cell biology to biomedicine. With the advent of DNA nanotechnology, the
programmable self-assembly ability makes DNA an appealing candidate for rational
design of artificial components with different structures and functions. This
Forum Article summarizes recent developments of DNA nanotechnology in mimicking
the structures and functions of existing cellular components. We highlight key
successes in the achievements of DNA-based biomimetic membrane proteins and
discuss the assembly behavior of these artificial proteins. Then, we focus on the
construction of higher-order structures by DNA nanotechnology to recreate cell
like structures. Finally, we explore the current challenges and speculate on
future directions of DNA nanotechnology in biomimetics.
PMID- 29939003
TI - Perovskite Photovoltaic Integrated CdS/TiO2 Photoanode for Unbiased
Photoelectrochemical Hydrogen Generation.
AB - Photoelectrolysis of water using solar energy into storable and environment
friendly chemical fuel in the form of hydrogen provides a potential solution to
address the environmental concerns and fulfill future energy requirements in a
sustainable manner. Achieving efficient and spontaneous hydrogen evolution in
water using solar light as the only energy input is a highly desirable but a
difficult target. In this work, we report perovskite solar cell integrated CdS
based photoanode for unbiased photoelectrochemical hydrogen evolution. An
integrated tandem device consisting of mesoporous CdS/TiO2 photoanode paired with
a triple-cation perovskite (Cs0.05(MA0.17FA0.83)0.95Pb(I0.83Br0.17)3) solar cell
is developed via a facile fabrication route. The proposed photovoltaic integrated
photoanode presents an efficient tandem configuration with high optical
transparency to long-wavelength photons and strong photoelectrochemical
conversions from short-wavelength photons. On the basis of this integrated tandem
device, an unbiased photocurrent density of 7.8 mA/cm2 is demonstrated under
AM1.5G illumination.
PMID- 29939005
TI - Atomically Thin p-n/p-n Nanodevices by Surface Charge Transfer Doping of
Arsenene/Antimonene Heterostructures.
AB - Surface charge transfer doping (SCTD) is a promising technique to construct high
performance nanodevices because of its high reproducibility and high spatial
selectivity and because it does little harm to the host semiconductor. Here, we
performed a first-principles theoretical investigation to assess the effects of
SCTD on the properties of two-dimensional (2D) arsenene, antimonene, and
arsenene/antimonene van der Waals heterostructure as well. It was found that
doping O or S on the surfaces of arsenene and antimonene could achieve efficient
p-type doping, while doping Cs2CO3 on them could achieve n-type doping.
Furthermore, when O and Cs2CO3 were co-doped on the two sides of the
arsenene/antimonene heterostructure, a typical type-ii energy band alignment can
be formed in O-arsenene/Cs2CO3-antimonene heterostructure, which effectively
extends the range of the light absorption into the near-infrared region and
facilitates the spatial separation of photogenerated electron-hole pairs. O- or S
doped arsenene and antimonene have tunable band gaps varying from 1.20 to 0.54 eV
because of the doping-induced change of the conduction band minima (CBM), and
Cs2CO3-doped arsenene and antimonene have band gaps of 2.02 and 1.36 eV,
respectively, because of the changes of both valence band maxima and CBMs. This
work offers a way to design p-n junctions with a tunable character, and the 2D p
n/p-n O-arsenene/Cs2CO3-antimonene heterostructure might be applied to electronic
and optoelectronic nanodevices.
PMID- 29939006
TI - Solution-Plasma-Assisted Bimetallic Oxide Alloy Nanoparticles of Pt and Pd
Embedded within Two-Dimensional Ti3C2T x Nanosheets as Highly Active
Electrocatalysts for Overall Water Splitting.
AB - Exploiting high-efficiency and low-cost bifunctional electrocatalysts for the
hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) has been
actively encouraged because of their potential applications in the field of clean
energy. In this paper, we reported a novel electrocatalyst based on an exfoliated
two-dimensional (2D) MXene (Ti3C2T x) loaded with bimetallic oxide alloy
nanoparticles (NPs) of Pt and Pd (represented by PtO aPdO bNPs@Ti3C2T x), which
was synthesized via solution plasma (SP) modification. The prepared materials
were then utilized as highly efficient bifunctional electrocatalysts toward the
HER and OER in alkaline solution. At a high plasma input power (200 W),
bimetallic oxide alloy nanoparticles of Pt and Pd or nanoclusters with different
metallic valence states were deposited onto the Ti3C2T x nanosheets. Because of
the synergism of the noble-metal NPs and the Ti3C2T x nanosheets, the
electrocatalytic results revealed that the as-prepared PtO aPdO bNPs@Ti3C2T x
nanosheets under the plasma input power of 200 W for 3 min only required a low
overpotential to attain 10 mA cm-2 for the HER (-26.5 mV) in 0.5 M H2SO4 solution
and OER (1.54 V) in 0.1 M KOH solution. Moreover, water electrolysis using this
catalyst achieved a water splitting current density of 10 mA cm-2 at a low cell
voltage of 1.53 V in 1.0 M KOH solution. These results suggested that the
hybridization of the extremely low usage of PtO a/PdO b NPs (1.07 MUg cm-2) and
Ti3C2T x nanosheets by SP will expand the applications of other clean energy
reactions to achieve sustainable energy.
PMID- 29939007
TI - Highly Thermally Conductive Composite Films Based on Nanofibrillated Cellulose in
Situ Coated with a Small Amount of Silver Nanoparticles.
AB - In this paper, a freestanding flexible nanofibrillated cellulose (NFC)/silver
(Ag) composite film with high thermal conductivity (TC) was prepared using the
NFC that was in situ coated with a small amount of Ag nanoparticles through
mussel-inspired chemistry of dopamine. The results demonstrated that Ag
nanoparticles were homogeneously coated on the surface of NFC nanofibers and
their incorporation had little influence on the film-forming ability of NFC. The
NFC decorated with Ag nanoparticles could easily form thermally conductive
pathways in the composite films, and the resultant films containing only 2.0 vol
% of Ag showed a high in-plane TC value of 6.0 W/(m.K), which was 4 times that of
pure NFC film. Moreover, the composite films exhibited relatively high strength
and flexibility. The highly thermally conductive NFC/Ag composite films possess
potential applications as lateral heat spreaders in flexible electronic
equipment.
PMID- 29939008
TI - Critical Impact of Solvent Evaporation on the Resolution of Inkjet Printed
Nanoparticles Film.
AB - We first verify the critical role of solvent evaporation on the resolution of
inkjet printing. To confirm our hypothesis, we adjusted the evaporation rate
gradient along the surface of adjacent droplets by controlling the drying
microenvironment. Uneven solvent evaporation flux caused thermocapillary surface
flow inward the space of micrometer-sized droplets and increase the air pressure,
which prevented the neighboring droplets from coalescence. When reducing the
droplet distance by the solvent evaporation-based method, a uniform profile could
be obtained at the same time. This work brings us a step closer to resolving one
of the critical bottlenecks to commercializing printed electronic goods.
PMID- 29939009
TI - Engineering the Slow Photon Effect in Photoactive Nanoporous Anodic Alumina
Gradient-Index Filters for Photocatalysis.
AB - In this study, we explore for the first time the capabilities of nanoporous
anodic alumina gradient-index filters (NAA-GIFs) functionalized with titanium
dioxide (TiO2) photoactive layers to enhance photon-to-electron conversion rates
and improve the efficiency of photocatalytic reactions by "slow photon" effect. A
set of NAA-GIFs was fabricated by sinusoidal pulse anodization, in which a
systematic modification of various anodization parameters (i.e., pore widening
time, anodization period, and anodization time) enables the fine-tuning of the
photonic stopband (PSB) of these nanoporous photonic crystals (PCs) across the
spectral regions. The surface of NAA-GIFs was chemically modified with
photoactive layers of TiO2 to create a composite photoactive material with
precisely engineered optical properties. The photocatalytic performance of TiO2
functionalized NAA-GIFs was assessed by studying the photodegradation of three
model organic dyes (i.e., methyl orange, Rhodamine B, and methylene blue) with
well-defined absorption bands across different spectral regions under simulated
irradiation conditions. Our study demonstrates that when the edges of
characteristic PSB of TiO2-modified NAA-GIFs are completely or partially aligned
with the absorption band of the organic dyes, the photodegradation rate is
enhanced due to "slow photon" effect. A rational design of the photocatalyst
material with respect to the organic dye is demonstrated to be optimal to speed
up photocatalytic reactions by an efficient management of photons from high
irradiance spectral regions. This provides new opportunities to develop high
performing photocatalytic materials for efficient photocatalysis with broad
applicability.
PMID- 29939010
TI - Correction to Twists and Turns of Orbiting and Spinning Metallic Microparticles
Powered by Megahertz Ultrasound.
PMID- 29939011
TI - Correction to Compartment-Specific Labeling of Bacterial Periplasmic Proteins by
Peroxidase-Mediated Biotinylation.
PMID- 29939012
TI - Ionic Current Behaviors of Dual Nano- and Micropipettes.
AB - Ionic current rectification (ICR) phenomena within dual glass pipettes are
investigated for the first time. We demonstrate that the ionic flow presents
different behaviors in dual nano- and micropipettes when the two channels are
filled with the same electrolyte KCl and hung in air. Bare dual nanopipettes
cannot rectify the ionic current because of their geometric symmetry, but the ICR
can be directly observed based on bare dual micropipettes. The phenomena based on
dual micropipettes could be explained by the simulation of the Poisson-Nernst
Plank equation. After modification with different approaches, the dual
nanopipettes have asymmetric charge patterns and show various ICR behaviors. They
have been successfully employed to fabricate various nanodevices, such as ionic
diodes and bipolar junction transistors. Due to the simple and fast fabrication
with high reproducibility, these dual pipettes can provide a novel platform for
controlling ionic flow in nano- and microfluidics, fabrication of novel
nanodevices, and detection of biomolecules.
PMID- 29939013
TI - Probe-Sample Interaction-Independent Atomic Force Microscopy-Infrared
Spectroscopy: Toward Robust Nanoscale Compositional Mapping.
AB - Nanoscale topological imaging using atomic force microscopy (AFM) combined with
infrared (IR) spectroscopy (AFM-IR) is a rapidly emerging modality to record
correlated structural and chemical images. Although the expectation is that the
spectral data faithfully represents the underlying chemical composition, the
sample mechanical properties affect the recorded data (known as the probe-sample
interaction effect). Although experts in the field are aware of this effect, the
contribution is not fully understood. Further, when the sample properties are not
well-known or when AFM-IR experiments are conducted by nonexperts, there is a
chance that these nonmolecular properties may affect analytical measurements in
an uncertain manner. Techniques such as resonance-enhanced imaging and
normalization of the IR signal using ratios might improve fidelity of recorded
data, but they are not universally effective. Here, we provide a fully analytical
model that relates cantilever response to the local sample expansion which opens
several avenues. We demonstrate a new method for removing probe-sample
interaction effects in AFM-IR images by measuring the cantilever responsivity
using a mechanically induced, out-of-plane sample vibration. This method is then
applied to model polymers and mammary epithelial cells to show improvements in
sensitivity, accuracy, and repeatability for measuring soft matter when compared
to the current state of the art (resonance-enhanced operation). Understanding of
the sample-dependent cantilever responsivity is an essential addition to AFM-IR
imaging if the identification of chemical features at nanoscale resolutions is to
be realized for arbitrary samples.
PMID- 29939014
TI - Combining Mass Spectrometry, Surface Acoustic Wave Interaction Analysis, and Cell
Viability Assays for Characterization of Shiga Toxin Subtypes of Pathogenic
Escherichia coli Bacteria.
AB - Shiga toxin (Stx)-producing Escherichia coli (STEC) and enterohemorrhagic E. coli
(EHEC) as a human pathogenic subgroup of STEC are characterized by releasing Stx
AB5-toxin as the major virulence factor. Worldwide disseminated EHEC strains
cause sporadic infections and outbreaks in the human population and swine
pathogenic STEC strains represent greatly feared pathogens in pig breeding and
fattening plants. Among the various Stx subtypes, Stx1a and Stx2a are of eminent
clinical importance in human infections being associated with life-threatening
hemorrhagic colitis and hemolytic uremic syndrome, whereas Stx2e subtype is
associated with porcine edema disease with a generalized fatal outcome for the
animals. Binding toward the glycosphingolipid globotriaosylceramide (Gb3Cer) is a
common feature of all Stx subtypes analyzed so far. Here, we report on the
development of a matched strategy combining (i) miniaturized one-step affinity
purification of native Stx subtypes from culture supernatant of bacterial wild
type strains using Gb3-functionalized magnetic beads, (ii) structural analysis
and identification of Stx holotoxins by electrospray ionization ion mobility mass
spectrometry (ESI MS), (iii) functional Stx-receptor real-time interaction
analysis employing the surface acoustic wave (SAW) technology, and (iv) Vero cell
culture assays for determining Stx-caused cytotoxic effects. Structural
investigations revealed diagnostic tryptic peptide ions for purified Stx1a,
Stx2a, and Stx2e, respectively, and functional analysis resulted in
characteristic binding kinetics of each Stx subtype. Cytotoxicity studies
revealed differing toxin-mediated cell damage ranked with Stx1a > Stx2a > Stx2e.
Collectively, this matched procedure represents a promising clinical application
for the characterization of life-endangering Stx subtypes at the protein level.
PMID- 29939015
TI - On-Capillary Surface-Enhanced Raman Spectroscopy: Determination of Glutathione in
Whole Blood Microsamples.
AB - Oxidative stress monitoring in the neonatal period supports early outcome
prediction and treatment. Glutathione (GSH) is the most abundant antioxidant in
most cells and tissues, including whole blood, and its usefulness as a biomarker
has been known for decades. To date, the available methods for GSH determination
require laborious sample processing and the use of sophisticated laboratory
equipment. To the best of our knowledge, no tools suitable for point-of-care
(POC) sensing have been reported. Surface-enhanced Raman spectroscopy (SERS),
performed in a microvolume capillary measurement cell, is proposed in this study
as a robust approach for the quantification of GSH in human whole blood samples.
The use of a silver colloid allowed a highly selective signal enhancement for GSH
providing analytical enhancement factors of 3 to 4 orders of magnitude. A highly
accurate determination of GSH in whole blood samples with recoveries ranging from
99 to 107% and relative standard deviations less than or equal to 18% were
achieved by signal normalization with the intensity of an isotopically labeled
internal standard. GSH concentrations were retrieved within 4 min using small
volume blood samples (2 MUL). The developed procedure was applied to the analysis
of blood of 20 healthy adults and 36 newborns, obtaining comparable results
between literature and those found by SERS and a reference method. The
characteristics of this novel tool are suitable for its implementation in a
portable optical sensor device enabling POC testing of oxidative stress levels in
newborns.
PMID- 29939016
TI - Graphite Intercalation by Mg Diamine Complexes.
AB - The first structural and compositional details of a low-stage graphite
interaction compound (GIC) containing Mg are reported, with the GIC obtained by
combining magnesium metal and graphite powder in ethylenediamine (en) at 100
degrees C under an inert atmosphere. Thermal analyses indicate the bottle-green
stage 1 product has a composition of [Mg(en)1.0]C13. X-ray diffraction shows a c
axis expansion of 0.55 nm, indicating the presence of intercalate monolayers with
the en cointercalate oriented perpendicular to the encasing graphene layers.
Redox titration indicates two electrons are transferred per Mg. A structural
model is proposed with dimeric [Mg2(en)2]2+ intercalate species.
PMID- 29939018
TI - Cancer Metabolism: Current Understanding and Therapies.
AB - Dysregulation of cancer cell metabolism contributes to abnormal cell growth, the
biological end point of cancer. We review here numerous affected oncogenes and
metabolic pathways common in cancer and how they contribute to cancer
pathogenesis and malignancy. This review also discusses various pharmacological
manipulations that take advantage of these metabolic abnormalities and the
current targeted therapies that have arisen from this research.
PMID- 29939019
TI - Conformational Dynamics of thiM Riboswitch To Understand the Gene Regulation
Mechanism Using Markov State Modeling and the Residual Fluctuation Network
Approach.
AB - Thiamine pyrophosphate (TPP) riboswitch is a cis-regulatory element in the
noncoding region of mRNA. The aptamer domain of TPP riboswitch detects the high
abundance of coenzyme thiamine pyrophosphate (TPP) and modulates the gene
expression for thiamine synthetic gene. The mechanistic understanding in
recognition of TPP in aptamer domain and ligand-induced compactness for folding
of expression platform are most important to designing novel modulators. To
understand the dynamic behavior of TPP riboswitch upon TPP binding, molecular
dynamics simulations were performed for 400 ns in both apo and TPP bound forms of
thiM riboswitch from E. coli and analyzed in terms of eRMSD-based Markov state
modeling and residual fluctuation network. Markov state models show good
correlations in transition probability among metastable states from simulated
trajectory and generated models. Structural compactness in TPP bound form is
observed which is correlated with SAXS experiment. The importance of junction of
P4 and P5 is evident during dynamics, which correlates with FRET analysis. The
dynamic nature of two sensor forearms is due to the flexible P1 helix, which is
its intrinsic property. The transient state in TPP-bound form was observed in the
Markov state model, along with stable states. We believe that this transient
state is responsible to assist the influx and outflux of ligand molecule by
creating a solvent channel around the junction region of P4 and P5 and such a
structure was anticipated in FRET analysis. The dynamic nature of riboswitch is
dependent on the interaction between residues on distal loops L3 and L5/P3 and
junction P4 and P5, J3/2 which stabilize the J2/4. It helps in the transfer of
allosteric information between J2/4 and P3/L5 tertiary docking region through the
active site residues. Understanding such information flow will benefit in
highlighting crucial residues in highly dynamic and kinetic systems. Here, we
report the residues and segments in riboswitch that play vital roles in providing
stability and this can be exploited in designing inhibitors to regulate the
functioning of riboswitches.
PMID- 29939020
TI - Impact of Disordered Guest-Framework Interactions on the Crystallography of Metal
Organic Frameworks.
AB - It is a general and common practice to carry out single-crystal X-ray diffraction
experiments at cryogenic temperatures in order to obtain high-resolution data. In
this report, we show that this practice is not always applicable to metal-organic
frameworks (MOFs), especially when these structures are highly porous.
Specifically, two new MOFs are reported here, MOF-1004 and MOF-1005, for which
the collection of the diffraction data at lower temperature (100 K) did not give
data of sufficient quality to allow structure solution. However, collection of
data at higher temperature (290 K) gave atomic-resolution data for MOF-1004 and
MOF-1005, allowing for structure solution. We find that this inverse behavior,
contrary to normal practice, is also true for some well-established MOFs (MOF-177
and UiO-67). Close examination of the X-ray diffraction data obtained for all
four of these MOFs at various temperatures led us to conclude that disordered
guest-framework interactions play a profound role in introducing disorder at low
temperature, and the diminishing strength of these interactions at high
temperatures reduces the disorder and gives high-resolution diffraction data. We
believe our finding here is more widely applicable to other highly porous MOFs
and crystals containing highly disordered molecules.
PMID- 29939021
TI - Total Synthesis of Aplysiasecosterol A.
AB - Aplysiasecosterol A (1) is a structurally unusual 9,11-secosteroid isolated from
the sea hare Aplysia kurodai. We have accomplished the first and asymmetric total
synthesis of 1 in a convergent fashion. The left-hand segment bearing three
adjacent stereocenters was constructed through desymmetrizing reduction,
ketalization, and radical cyclization. A strategy of asymmetric 2-bromoallylation
followed by spontaneous desymmetrizing lactolization enabled a more expeditious
access to this segment. The right-hand segment was prepared through two different
approaches: one featuring Myers alkylation and Suzuki-Miyaura coupling and the
other relying upon Aggarwal lithiation-borylation and Zweifel-Evans olefination.
The two fragments were coupled by a Reformatsky type reaction. The three
consecutive stereocenters embedded in the central domain of 1 were generated by
an iron-mediated, hydrogen atom transfer based radical cyclization reaction.
PMID- 29939022
TI - Sonochemical Synthesis of Small Boron Oxide Nanoparticles.
AB - The synthesis of small boron oxide nanoparticles (NPs) is reported. A
sonochemical approach in the presence of a capping agent was employed to produce
approximately 4-5-nm-sized B2O3 NPs, including the 10B isotopically enriched
form. The morphology and composition of the NPs were established using
transmission electron microscopy and diffraction, respectively. X-ray
photoelectron and Fourier transform infrared spectroscopies provided information
about surface functionalization of the B2O3 NPs, which can be further modified
through a facile, one-step ligand-exchange process. The toxicity of the
synthesized NPs was investigated in Chinese hamster ovarian cells, indicating
that these systems were nontoxic up to 1.7 mM concentrations.
PMID- 29939023
TI - Complexes Bearing Protic N-Heterocyclic Carbene Ligands.
AB - Complexes bearing protic N-heterocyclic carbenes (protic NHCs, pNHCs), defined as
cyclic carbenes stabilized by two heteroatoms including at least one NH group,
have been less explored in comparison to the conventional N,N'-disubstituted
NHCs. The small and reactive NH group of the pNHCs differentiates this class of
compounds from the classical NR,NR-NHCs with regard to their properties and
reactivity. While the free pNHCs have so far eluded isolation due to
isomerization to the azole tautomer, a significant number of transition-metal
pNHC complexes have by now been prepared by a variety of methods. This article
reviews the coordination chemistry of the pNHCs. Synthetic approaches toward
complexes of pNHCs are first described, followed by a discussion of the
properties and reactivity of pNHC complexes with emphasis on the Bronsted-acidic
nature of the NH wingtip. Involvement of the pNHC ligands in catalytically active
intermediates and in cooperative catalysis is also discussed.
PMID- 29939024
TI - Chiral Diaryliodonium Phosphate Enables Light Driven Diastereoselective alpha
C(sp3)-H Acetalization.
AB - C(sp3)-H bond functionalization has emerged as a robust tool enabling rapid
construction of molecular complexity from simple building blocks, and the
development of asymmetric versions of this reaction creates a powerful
methodology to access enantiopure sp3-rich materials. Herein, we report the
stereoselective functionalization of C(sp3)-H bonds of cyclic ethers employing a
photochemically active diaryliodonium salt in combination with an anionic phase
transfer catalyst. The synthetic strategy outlined herein allows for regio- and
stereochemical control in the alpha-C-H acetalization of furans and pyrans using
alcohol nucleophiles, thus providing the ability to control the configuration at
the stereogenic exocyclic acetal carbon.
PMID- 29939025
TI - PGK1 Promoter Library for the Regulation of Acetate Ester Production in
Saccharomyces cerevisiae during Chinese Baijiu Fermentation.
AB - Appropriate concentrations and proportion of acetate esters and higher alcohols
improve the quality of Chinese Baijiu. To regulate the concentrations of acetate
esters in Chinese Baijiu, we constructed a PGK1 promoter library through error
prone PCR. Then, we used an enhanced green fluorescent protein as a reporter to
characterize the activities of PGK1p mutants. The PGK1p library contained 28
PGK1p mutants and spanned an activity that ranged between 0.1% and 141% of wild
type PGK1p. Seven PGK1p mutants were characterized by an additional reporter beta
galactosidase and then used for the overexpression of ATF1 with BAT2 deletion in
Saccharomyces cerevisiae a45. The production of ethyl acetate in strains A8, A17,
A18, A27, A22, A25, A28, and AWT were 1.66-, 3.09-, 10.59-, 13.07-, 15.99-, 22.67
, 24.06-, and 27.22-fold higher than that of the parental strain. The results on
alcohol acetyltransferase (AATase) activity showed that the PGK1p library
precisely controlled ATF1 expression and regulated the acetate esters production.
PMID- 29939026
TI - High Accuracy Quantum Chemical and Thermochemical Network Data for the Heats of
Formation of Fluorinated and Chlorinated Methanes and Ethanes.
AB - Reliable heats of formation are reported for numerous fluorinated and chlorinated
methane and ethane derivatives by means of an accurate thermochemical protocol,
which involves explicitly correlated coupled-cluster calculations augmented with
anharmonic, scalar relativistic, and diagonal Born-Oppenheimer corrections. The
theoretical results, along with additional experimental data, are further
enhanced with the help of the thermochemical network approach. For 28 species,
out of 50, this study presents the best estimates, and discrepancies with
previous reports are also highlighted. Furthermore, the effects of the less
accurate theoretical data on the results yielded by thermochemical networks are
discussed.
PMID- 29939027
TI - N-Monomethylation of Aromatic Amines with Methanol via PNHP-Pincer Ru Catalysts.
AB - The use of methanol for the selective methylation of aromatic amines with
RuHCl(CO)(PNHP) (PNHP = bis(2-diphenylphosphinoethyl)amine) is reported. Various
aromatic amines were transformed into their corresponding monomethylated
secondary amines in high yields at 150 degrees C with a very low catalyst
loading (0.02-0.1 mol %) in the presence of KO tBu (20-60 mol %). The catalyst
precursor, RuHCl(CO)(PNHP), was converted to [RuH(CO)2(PNHP)]+ under the
catalytic conditions and also serves as a highly effective catalyst. The
robustness of this catalyst contributes to its outstanding catalytic activity,
even under reaction conditions, in which CO is liberated from methanol.
PMID- 29939028
TI - Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo
Analgesic Activity.
AB - TRPM8 has been implicated in nociception and pain and is currently regarded as an
attractive target for the pharmacological treatment of neuropathic pain
syndromes. A series of analogues of N, N'-dibenzyl tryptamine 1, a potent TRPM8
antagonist, was prepared and screened using a fluorescence-based in vitro assay
based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells.
The tryptophan derivative 14 was identified as a potent (IC50 0.2 +/- 0.2 nM) and
selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in
both an icilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold
allodynia (at 0.1-1 MUg s.c.) mice models. Molecular modeling studies identified
the putative binding mode of these antagonists, suggesting that they could
influence an interaction network between the S1-4 transmembrane segments and the
TRP domains of the channel subunits. The tryptophan moiety provides a new
pharmacophoric scaffold for the design of highly potent modulators of TRPM8
mediated pain.
PMID- 29939030
TI - Thermoinduced Free-Radical C-H Acyloxylation of Tertiary Enaminones: Catalyst
Free Synthesis of Acyloxyl Chromones and Enaminones.
AB - In this paper, the direct acyloxylation of the alpha-C(sp2)-H bond in tertiary
beta-enaminones is accomplished under catalyst-free conditions and ambient
temperature by using aroyl peroxides as coupling partners. By means of a
thermoinduced free-radical pathway, the present method enables facile and
efficient synthesis of both acyloxylated chromones and enaminones.
PMID- 29939029
TI - Metabolic Profiling of Chloroacetanilide Herbicides in Earthworm Coelomic Fluid
Using 1H NMR and GC-MS.
AB - Earthworms ( Eisenia fetida) are vital members of the soil environment. Because
of their sensitivity to many contaminants, monitoring earthworm metabolism may be
a useful indicator of environmental stressors. Here, metabolic profiles of
exposure to five chloroacetanilide herbicides and one enantiomer (acetochlor,
alachlor, butachlor, racemic metolachlor, S-metolachlor, and propachlor) are
observed in earthworm coelomic fluid using proton nuclear magnetic resonance
spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS). Multiblocked
orthogonal partial least-squares-discriminant analysis (MB-OPLS-DA) and
univariate analysis were used to identify metabolic perturbations in carnitine
biosynthesis, carbohydrate metabolism, lipid metabolism, nitrogen metabolism, and
the tricarboxylic acid cycle. Intriguingly, stereospecific metabolic responses
were observed between racemic metolachlor and S-metolachlor exposed worms. These
findings support the utility of coelomic fluid in monitoring metabolic
perturbations induced by chloroacetanilide herbicides in nontarget organisms and
reveal specificity in the metabolic impacts of herbicide analogues in earthworms.
PMID- 29939031
TI - Rhodium(I)-Catalyzed Coupling-Cyclization of C?O Bonds with alpha-Diazoketones.
AB - An unprecedented intermolecular nucleophilic attack of C?X bonds (X = O and S) on
the rhodium(I)-carbenes has been developed. This transformation allows for the
coupling-cyclization of aroylamides with alpha-diazoketones and provides concise
access to 2,4,5-trisubstituted 1,3-oxazoles and 1,3-thiazoles with a broad
tolerance of functional groups.
PMID- 29939032
TI - Base-Mediated Cascade Cyclization: Stereoselective Synthesis of Benzooxazocinone.
AB - A new strategy for the synthesis of the oxa-azabicyclo[3.3.1]nonane subunit, a
component of the naucleamide E core structure, has been developed. This
annulation reaction between 1-substituted 3,4-dihydroisoquinolines and coumarin
derivatives conveniently affords the oxa-azabicyclo[3.3.1]nonane framework via a
base-mediated cascade cyclization under aqueous conditions. The value of this
work lies in the efficient formation of the oxa-azabicyclo[3.3.1]nonane skeleton
via a process whereby all the C-C, C-O, and C-N bond formations occur in a single
chemical operation. In addition, the subsequent ring opening of these compounds
furnished pyridoisoquinoline derivatives.
PMID- 29939033
TI - Synthesis of the Aminocyclitol Core of Jogyamycin via an Enantioselective Pd
Catalyzed Trimethylenemethane (TMM) Cycloaddition.
AB - The use of beta-nitroenamines as a new class of acceptors in the enantioselective
Pd-catalyzed trimethylenemethane cycloaddition afforded differentiated 1,2
dinitrogen bearing cyclopentanes with three contiguous stereocenters. The utility
of these acceptors was demonstrated with the efficient construction of the core
of jogyamycin and aminocyclopentitols. Further elaboration of the cycloadducts
provided a concise synthetic approach toward joygamycin.
PMID- 29939034
TI - Correction to Total Syntheses of 7,20-Oxa-Bridged Dinorditerpenes: Antihepatitis
C Virus Active (+)-Elevenol from Flueggea virosa and (+)-Przewalskin.
PMID- 29939035
TI - Nonlinear consequences of promotive and prohibitive voice for managers'
responses: The roles of voice frequency and LMX.
AB - Departing from past research on managers' responses to employee voice, we propose
and examine a nonlinear linkage between promotive/prohibitive voice and managers'
evaluations of voicers (i.e., manager-rated voicers' promotability and overall
performance). Drawing from social persuasion theory, we theorize that managers
tend to give more positive evaluations to employees who engage in a moderate
frequency of promotive/prohibitive voice than those who either rarely speak up or
speak up very frequently. In Study 1, based on a sample from a Chinese bank, we
found that leader-member exchange quality (LMX) moderated the inverted U-shaped
linkage of prohibitive voice with manager-rated promotability of voicers, whereas
the frequency of promotive voice was not related to promotability, irrespective
of levels of LMX. In Study 2, using employee-reported voice frequency, rather
than the manager-rated measures adopted in Study 1, we largely replicated the
main findings of Study 1 based on a sample from an information technology firm in
the United States. In Study 3, using another U.S. sample, from a financial
services firm, we found that manager-perceived voice constructiveness mediated
the curvilinear interactive effect of prohibitive voice (rather than promotive
voice) and LMX on managers' evaluations of employees' overall performance.
(PsycINFO Database Record (c) 2018 APA, all rights reserved).
PMID- 29939036
TI - Good actors but bad apples: Deviant consequences of daily impression management
at work.
AB - Impression management (IM) refers to behaviors employees use to create and
maintain desired images in the workplace. Prior studies have shown that the
successful use of IM relates to a number of important outcomes for employees
(e.g., higher performance evaluations), but this work has tended to compare IM
usage between individuals, ignoring the fact that employees likely adjust their
use of IM depending on the situations they face at work on a given day. In this
paper, we argue that managing impressions on a daily basis can be draining,
thereby leaving employees susceptible to the temptation to engage in subsequent
harmful behaviors at work. To better understand the nature and within-person
consequences of IM, we examine the daily use of two supervisor-focused IM tactics
ingratiation and self-promotion-among 75 professionals in China over the course
of two work weeks. Our results indicate that there is significant within-person
variance in employees' use of ingratiation and self-promotion aimed at
supervisors. Moreover, our findings suggest that the use of ingratiation, but not
self-promotion, depletes employees' self-control resources. In the case of
ingratiation, this depletion is positively associated with employee deviance, and
the indirect effect is stronger among employees with low political skill.
Overall, this research contributes to our understanding of the dynamic, within
person nature of IM, the consequences of IM for employees, and the dark side of
IM for organizations. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29939037
TI - Changing experiences of work dirtiness, occupational disidentification, and
employee withdrawal.
AB - Research and theory concerning "dirty work" has largely focused on how employees
cope with stable features of their jobs. From a study of employees' experiences
across 6 weekly repeated measurements, we found that within-person increases in
experienced dirtiness were positively related to their withdrawal behaviors and
job change propensity indirectly through occupational disidentification. Assessed
at the between-subjects level, team-oriented leadership moderated the indirect
within-person effects of work dirtiness experiences on these outcomes. The
relationships between elevations in experienced work dirtiness and occupational
disidentification were more strongly positive at lower levels of team-oriented
leadership. Analyses also showed that individuals' perceptions of occupational
stigma independently moderated the within-person relationship between experienced
dirtiness and occupational disidentification. We discuss theoretical implications
for the literature on dirty work and practical implications for mitigating the
adverse outcomes associated with experienced work dirtiness. (PsycINFO Database
Record (c) 2018 APA, all rights reserved).
PMID- 29939038
TI - Cohort effects in children's delay of gratification.
AB - In the 1960s at Stanford University's Bing Preschool, children were given the
option of taking an immediate, smaller reward or receiving a delayed, larger
reward by waiting until the experimenter returned. Since then, the "Marshmallow
Test" has been used in numerous studies to assess delay of gratification. Yet, no
prior study has compared the performance of children across the decades. Common
wisdom suggests children today would wait less long, preferring immediate
gratification. Study 1 confirmed this intuition in a survey of adults in the
United States (N = 354; Mdn age = 34 years). To test the validity of this
prediction, Study 2 analyzed the original data for average delay-of-gratification
times (out of 10 min) of 840 typically developing U.S. children in three birth
cohorts from similar middle-high socioeconomic backgrounds in the late 1960s,
1980s, and 2000s, matched on age (3 to 5 years) at the time of testing. In
contrast to popular belief, results revealed a linear increase in delay over time
(p < .0001, etap2 = .047), such that children in the 2000s waited on average 2
min longer than children in the 1960s, and 1 min longer than children in the
1980s. This pattern was robust with respect to age, sex, geography and sampling
effects. We posit that increases in symbolic thought, technology, preschool
education, and public attention to executive function skills have contributed to
this finding, but caution that more research in diverse populations is needed to
examine the generality of the findings and to identify causal factors. (PsycINFO
Database Record
PMID- 29939039
TI - Reassessing the good judge of personality.
AB - Are some people truly better able to accurately perceive the personality of
others? Previous research suggests that the good judge may be of little practical
importance and individual differences minimal. In four large samples we assessed
whether expressive accuracy (the good target) is a necessary condition for
perceptive accuracy (the good judge) to emerge. As predicted from Funder's (1995)
realistic accuracy model, assessments of the good judge predicted increased
impression accuracy in the context of judgments of the good target. In contrast,
evaluative tendencies for judges did not evidence a similar interaction; the
positivity of impressions did not reliably increase as a function of how
positively targets tend to be viewed. The present results suggest the good judge
does indeed exist-some individuals are much better able to detect and utilize
valid cues from targets-but this is only strongly evident when perceiving a good
target. (PsycINFO Database Record
PMID- 29939040
TI - Examining the reliability and factor structure of the Malay version of the
Recovery Self-Assessment in a sample of individuals with schizophrenia.
AB - OBJECTIVE: Without a reliable and valid tool, it is neither possible to gauge
recovery orientation of persons with serious mental illness nor to evaluate
whether existing mental health system encourages recovery in both its policies
and current practice in Malaysia. Therefore, the aim of this study was to examine
the reliability and factor structure of the Malay version of the Recovery Self
Assessment (RSA-PIRV-M) in a psychiatric sample. METHOD: Psychiatric patients
were eligible for recruitment to the study, when they fulfilled the following
criteria: a diagnosis of schizophrenia, were aged between 18- and 65-years-old,
and were able to give consent themselves. We recruited 118 individuals with
schizophrenia. They were selected via systematic random sampling technique. All
RSA-PIRV-M items were derived from the parent scale. These items were translated
based on established procedures. The reliability estimates of the RSA-PIRV-M were
based on Cronbach's alpha. We performed confirmatory factor analyses to examine
the factor structure of the RSA-PIRV-M. RESULTS: All Cronbach's alphas for the
RSA-PIRV-M subscales were at least .70. With respect to the factor structure of
the RSA-PIRV-M, our structural equation modeling findings suggest a five-factor
model encompassing life goals, involvement, diversity of treatment options,
choice, and individually-tailored services. CONCLUSIONS AND IMPLICATIONS FOR
PRACTICE: The interpretation of our findings is limited by small sample size,
unique sample characteristics, and lack of further evidence for convergent
validity. Notwithstanding these limitations, the RSA-PIRV-M is a promising tool
in bridging gaps between our knowledge on recovery orientation and existing
mental health service provision in Malaysia. (PsycINFO Database Record (c) 2018
APA, all rights reserved).
PMID- 29939041
TI - Marital processes linking economic hardship to mental health: The role of
neurotic vulnerability.
AB - Both enduring neurotic vulnerabilities and economic hardship have been shown to
negatively influence marital behaviors, which have physical and mental health
consequences. However, because most previous research is fragmented and has
focused on the early years of marriage or relatively short periods of time, their
long-term effects are unclear. Using data from the Iowa Midlife Transitions
Project, with a sample of 370 married couples providing data from 1991 to 2001,
we assessed enduring personal and couple vulnerabilities, trajectories of family
economic hardship, and couples' marital hostility using a comprehensive dyadic
model to ascertain their influence on subsequent mental health. Couple marital
hostility trajectories and neurotic vulnerabilities (both additively and
interactively) were associated with changes in both spouses' depressive symptoms.
Results also indicated that couples' marital hostility trajectories link
trajectories of family economic hardship to subsequent changes in husbands' and
wives' depressive symptoms. Last, associations between economic hardship
trajectories, marital hostility trajectories, and depressive symptoms were
moderated by couples' neurotic vulnerability as captured by a product term of
husbands' and wives' neurotic vulnerability. In general, these associations were
amplified for couples with a high level of couple vulnerability and weakened (or
altogether absent) for those with a low level of vulnerability. (PsycINFO
Database Record (c) 2018 APA, all rights reserved).
PMID- 29939042
TI - Patterns of stepfamily relationship quality and adolescents' short-term and long
term adjustment.
AB - Stepfamilies experience unique dynamics, with implications for family functioning
and youth well-being. Emerging research is incorporating a holistic perspective
whereby stepfamily dynamics are viewed more comprehensively, and constellations
of stepfamily relationship quality are identified. In the current study, we
examined short-term and long-term associations between latent patterns of
stepfamily relationships (including the quality of mother-child, stepfather
child, nonresident father-child, and stepcouple dyads) and youth adjustment
(i.e., depression, delinquency, self-esteem) across three stages of youth
development: adolescence, emerging adulthood, and young adulthood. Using a
representative sample of adolescents from the National Longitudinal Study of
Adolescent to Adult Health (Harris et al., 2009), results from longitudinal
structural equation models and latent-growth curve models indicated that youth
adjustment over time is optimized among youth in a residence-centered (i.e., high
quality relationships among mother-child, stepfather-child, and stepcouple dyads)
or inclusive (i.e., high-quality relationships across all dyads, including the
nonresident father) pattern, as compared with youth in an unhappy-couple (i.e.,
low-quality stepcouple relationship) or parent-child disconnection (i.e., low
quality relationships between youth and each parental figure) pattern. The
results point to many similarities between male and female youth in terms of
adjustment responses to patterns of stepfamily relationships, although some
differences became apparent. In the context of stepfamily relationships marked by
low-quality relationships, male youth might exhibit greater initial levels of
externalizing problems than female youth, whereas female youth might exhibit
greater initial levels of internalizing problems than male youth. Implications
for future research and intervention and prevention efforts are discussed.
(PsycINFO Database Record
PMID- 29939043
TI - Risks and rewards of school-based mentoring relationships: A reanalysis of the
student mentoring program evaluation.
AB - In the United States, school-based mentoring programs are a large and widely
funded form of mentoring. Despite widespread support, meta-analyses indicate that
the effects of school-based mentoring programs are small. One hypothesis for
these results is that school-based mentors are not able to develop a sufficiently
high-quality relationship with mentees to produce the hypothesized positive
effects. This study presents a reanalysis of a large randomized controlled trial
of school-based mentoring and examines the estimated effect of mentoring as a
function of mentee-reported relationship quality using a novel statistical
approach. Although we found that average effect sizes were near zero and
consistent with researchers' original findings, our findings also indicate that
low relationship quality is associated with some harmful effects, particularly on
misconduct, and that as relationship quality improves, so do effects. However, we
found that this association decelerates and resulted in small, positive effects
for some outcomes. These results suggest that that poor relationship quality may
produce harmful effects and a strong relationship may not be sufficient to
produce moderate, positive academic and behavioral outcomes in a school-based
mentoring context. (PsycINFO Database Record
PMID- 29939044
TI - Modeling intraindividual variation in unsafe driving in a naturalistic commuting
environment.
AB - Commuting to work by car is a frequently occurring activity that poses a salient
risk to worker safety. Although general stress perceptions have been linked to
indicators of unsafe commuting in cross-sectional studies, little is known about
whether and how day-to-day variability in stressor exposure and subjective and
affective strain reactions covary with intraindividual variability in unsafe
driving while commuting over time. A major contributor to this knowledge gap is
the lack of a validated methodology to link subjective self-report variables to
objective driving performance criteria in a naturalistic commuting environment.
Data were collected from university staff employees (N = 50) over a 2-week sample
of daily experiences and objective recordings of unsafe driving behaviors. We
applied a multilevel methodology to evaluate a model in which exposure to daily
hindering and challenging components of work stress, end-of-workday psychological
distress, and end-of-workday negative affect influence objectively monitored
unsafe driving behaviors in a naturalistic commuting environment. Results
indicated that employees were less likely to drive unsafely during their postwork
commute on days in which they encountered more challenge stressors at work (odds
ratio = .63). However, employees who experienced heightened negative affective
spillover were more likely to drive unsafely during their postwork commute (odds
ratio = 1.96). We discuss the theoretical, practical, and methodological
implications of our findings for research on employee commuting safety. (PsycINFO
Database Record
PMID- 29939045
TI - With a little help from my boss: The impact of workplace mental health training
on leader behaviors and employee resource utilization.
AB - Mental health problems are among the costliest issues facing organizations in the
developed world. In response to the mounting burdens surrounding poor employee
mental health, many organizations have introduced mental health promotion
programs and resources (e.g., employee assistance programs). Despite the rise in
available options, very few employees use these resources to their full
potential. Using a wait-list control design with random assignment, we evaluate
the impact of a leader-focused mental health training on employees' (N = 82;
51.25% response rate) resource use and leaders' (N = 37; 56.92% response rate)
communication about mental health and mental health resources. Based on other
report data from employees, leaders who received training shared more information
about mental health and mental health resources, were more supportive of
employees' mental health issues, and actively encouraged employees to use
available resources. Employees whose leaders attended the training also reported
increased willingness to seek out and use available resources. For leaders who
attend training and complete three waves of data collection, results suggest that
a 3-hr mental health training may lead to significant behavioral change up to 3
months posttraining. (PsycINFO Database Record
PMID- 29939046
TI - Initial development of pathological personality trait domain measures using the
Personality Assessment Inventory (PAI).
AB - This study set out to create measures of the five personality disorder trait
domains outlined in Section III of the Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition (American Psychiatric Association, 2013) from the
Personality Assessment Inventory items (Morey, 2007). Rasch rating scale model
analyses and classical test theory analyses were applied to existing data sets (N
= 3,877; community, clinical, offender, college) to identify relevant items. Five
scales were created that had acceptable unidimensionality and generally conformed
to Rasch model expectations. The ability of the items to cover the underlying
construct and their differential item function by sex were acceptable, though a
few of the proposed scales had weaknesses in these areas. Internal consistency
was acceptable for all scales and the factor structure was generally consistent
with expectations, but some scales had concerning cross-loadings. Preliminary
analyses demonstrated validity of the scales in relation to history of mental
health treatment/current symptoms, substance abuse, and, for one scale, violent
rearrests. There were small-to-moderate associations with noncorresponding
traits, suggesting a degree of saturation with general personality impairment.
The relevance of the proposed scales for the assessment of Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition personality disorder is
discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
PMID- 29939047
TI - Intrinsic whole number bias in humans.
AB - Humans have great difficulty comparing quotients including fractions,
proportions, and probabilities and often erroneously isolate the whole numbers of
the numerators and denominators to compare them. Some have argued that the whole
number bias is a compensatory strategy to deal with difficult comparisons. We
examined adult humans' preferences for gambles that differed only in numerosity,
and not in factors that influence their expected value (probabilities and
stakes). Subjects consistently preferred gambles with more winning balls to ones
with fewer, even though the probabilities were mathematically identical,
replicating prior results. In a second experiment, we found that subjects
accurately represented the relative probabilities of the choice options during
rapid nonverbal probability judgments but nonetheless showed biases based on
whole numbers. We mathematically formalized and quantitatively evaluated
cognitive rules based on existing hypotheses that attempt to explain subjects'
whole number biases during quotient comparisons. The results show that the whole
number bias is intrinsic to the way humans solve quotient comparisons rather than
a compensatory strategy. (PsycINFO Database Record
PMID- 29939048
TI - Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) and R(-) MDMA on
actigraphy-based daytime activity and sleep parameters in rhesus monkeys.
AB - 3,4-Methylenedioxymethamphetamine (MDMA) affects monoaminergic pathways that play
a critical role in sleep-wake cycles. Dopaminergic mechanisms are thought to
mediate the sleep-disrupting effects of stimulant drugs. However, the mechanisms
underlying the effects of MDMA on sleep-wake cycles and the effects of R(-) MDMA,
a stereoisomer that lacks dopaminergic activity, on sleep remain unknown. The aim
of the present study was to investigate the effects of racemic MDMA and R(-) MDMA
on daytime activity and sleep-like parameters evaluated with actigraphy in adult
rhesus macaques (Macaca mulatta, n = 6). Actiwatch monitors were attached to the
monkeys' collars and actigraphy recording was conducted during baseline
conditions and after the administration of acute intramuscular injections of
saline (vehicle), racemic MDMA (0.3, 1.0, or 1.7 mg/kg), or R(-) MDMA (0.3, 1.0,
or 1.7 mg/kg) at 9 or 16 h (3 h before "lights off"). Morning treatments had no
effects on sleep-like parameters. Racemic MDMA decreased general daytime activity
during the first hour after injection and increased daytime activity at 3 hr
posttreatment. Although afternoon administration of racemic MDMA increased sleep
latency, it improved other sleep parameters, decreasing wake time after sleep
onset (WASO) and increasing sleep efficiency for subjects with low baseline sleep
efficiency. Afternoon treatment with R(-) MDMA improved sleep measures,
increasing sleep efficiency and decreasing sleep latency and WASO, while having
no effects on daytime activity. The stimulant and sleep-disrupting effects of
racemic MDMA are likely mediated by dopaminergic and noradrenergic mechanisms,
while serotonergic pathways appear to be involved in the sleep-promoting effects
of MDMA. (PsycINFO Database Record
PMID- 29939049
TI - Interim buprenorphine treatment during delays to comprehensive treatment: Changes
in psychiatric symptoms.
AB - Prevalence of depression, anxiety, and mood disorders among individuals with
opioid use disorder far exceeds that of the general population. While psychiatric
symptoms often improve upon entry into opioid treatment, this has typically been
seen with treatments involving psychosocial counseling. In this secondary
analysis, we examined changes in psychiatric symptoms during a randomized
clinical trial evaluating an interim buprenorphine treatment without counseling
among individuals awaiting entry into comprehensive treatment. Waitlisted adults
with opioid use disorder (N = 50) were randomized to one of two 12-week
conditions: interim buprenorphine treatment (IBT; n = 25) consisting of
buprenorphine maintenance using a computerized medication dispenser, with
bimonthly clinic visits and technology-assisted monitoring, or waitlist control
(WLC; n = 25), wherein participants remained on the waitlist of their local
clinic. All participants completed assessments of psychiatric symptoms at intake
and Study Weeks 4, 8, and 12. We examined changes on the Beck Anxiety Inventory
(BAI), Beck Depression Inventory-II (BDI-II), Brief Symptom Inventory (BSI), and
Psychiatric subscale of the Addiction Severity Index (ASI). Significant group-by
time interactions were observed for all measures of psychiatric severity
examined: BAI (p < .05), BDI-II (p < .01), 5 BSI subscales (ps < .05), and the
ASI Psychiatric subscale (p < .05). On all measures, IBT participants reported
significantly reduced psychiatric severity at the 4-, 8-, and 12-week assessments
relative to baseline. In contrast, there were no significant changes in
psychiatric symptoms among WLC participants. IBT without counseling may improve
psychiatric distress among waitlisted individuals with opioid use disorder.
(PsycINFO Database Record
PMID- 29939050
TI - Impact of child and informant gender on parent and teacher ratings of attention
deficit/hyperactivity disorder.
AB - Attention-deficit/hyperactivity disorder (ADHD) rating scales typically provide
normative tables arranged according to child age, child gender, and type of
informant, which facilitates addressing the fifth edition of the Diagnostic and
Statistical Manual of Mental Health Disorders developmental deviance requirement
for diagnosing ADHD. Missing, however, is any consideration of the gender of the
informant. The purpose of this paper was to conduct an exploratory examination of
informant gender via secondary analyses of a large data set used to standardize
the ADHD Rating Scale-5. Two (informant gender) by two (child gender) ANOVAs were
conducted separately for parents and teachers using inattention (IN) symptoms,
hyperactive-impulsive (HI) symptoms, the total impairment score related to IN,
and the total impairment score for HI as dependent variables. Results showed that
female parents rated male children significantly higher on both IN symptoms and
impairment related to IN than did male parents. Female teacher ratings were also
significantly higher than male teacher ratings for male children in terms of HI
symptoms and with respect to impairment ratings related to both HI and IN. A
significantly higher percentage of female parents (7.7%) identified male children
as being at risk for ADHD relative to male parents (4.1%). This same pattern
emerged for female teachers (11.9%) versus male teachers (5.3%). Such results
suggest that informant gender may play a clinically meaningful role in assessing
ADHD in children and adolescents, which is consistent with the developmental
literature addressing gender stereotypes in children. Future research is needed
to determine whether similar informant gender differences exist in other rating
scale measures of ADHD. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29939051
TI - Brief mindfulness training for negative affectivity: A systematic review and meta
analysis.
AB - OBJECTIVE: Over the last 10 years, there has been a dramatic increase in
published randomized controlled trials (RCTs) of brief mindfulness training (from
single-session inductions to multisession interventions lasting up to 2 weeks),
with some preliminary indications that these training programs may improve mental
health outcomes, such as negative affectivity. This meta-analysis aimed to
evaluate whether brief mindfulness training reliably reduces negative
affectivity. METHOD: PubMed, PsycINFO, and the Mindfulness Research Monthly
Newsletter were systematically searched for brief mindfulness intervention RCTs
assessing negative affectivity outcomes (e.g., depression, rumination, anxiety,
stress). Sixty-five RCTs, including 5,489 participants predominantly without
experience in meditation (64.64% female, mean age = 24.62), qualified for the
meta-analytic review. RESULTS: The meta-analysis revealed a small but significant
effect of brief mindfulness training on reducing negative affectivity compared to
control programs (g = .21, p < .001). The overall effect size was significantly
moderated by participant characteristics: community samples (g = .41, p < .001)
produced larger training effects compared to student samples (g = .14, p = .001;
Qbetween p = .03). No significant effect size differences were found between
clinical and nonclinical samples. However, when accounting for publication bias,
the overall effect size of brief mindfulness training programs on negative
affectivity was significantly reduced (g = .04). CONCLUSIONS: Brief mindfulness
training programs are increasingly popular approaches for reducing negative
affectivity. This meta-analysis indicates that brief mindfulness training
modestly reduces negative affectivity. Quantitative analyses indicated the
presence of publication bias (i.e., unpublished null effect studies),
highlighting the need to continue rigorous evaluation of brief mindfulness
interventions. (PsycINFO Database Record
PMID- 29939052
TI - Common change factors and mediation of the alliance-outcome link during treatment
of depression.
AB - OBJECTIVE: Alliance, Mastery/Self-Efficacy, Problem Actualization, and Problem
Clarification exemplify common or nonspecific factors of change in psychotherapy
(Grawe, 1997). In this study, we tested the hypothesis that other change factors
mediate the alliance-outcome link on a within-person level over the treatment
course. METHOD: Our sample consisted of 193 patients with major depression
undergoing intensive inpatient cognitive-behavioral-based therapy. Each week, we
assessed depressive symptoms (using the Beck Depression Inventory-II) and change
factors during individual therapy. Multilevel mediation models were used to test
our hypothesis. RESULTS: As expected, within-person change in Alliance
(differentiated into Emotional Bond and Contentment with the Therapist) as well
as Mastery/Self-Efficacy and Problem Clarification predicted symptom change over
the course of therapy. Moreover, the relation between Contentment with the
Therapist and subsequent change in depression was mediated by increased
Mastery/Self-Efficacy on a within-person level. CONCLUSIONS: Our data suggest
that within-person change of alliance and other general change factors precede
symptom change in depressive patients, and that the link between alliance and
outcome may be partially mediated by enhanced Mastery/Self-Efficacy. Future
studies should further elucidate the mechanisms responsible for the alliance
outcome link. (PsycINFO Database Record
PMID- 29939053
TI - Emotion regulation and spillover of interpersonal stressors to postsession
insight among depressed and suicidal adolescents.
AB - OBJECTIVE: Little is known about the extent to which previous weeks' stressful
events spill over and influence adolescents' abilities to derive insight from
treatment sessions. Even less is known about factors that moderate clients'
vulnerabilities to these spillover effects. The current study examined the
spillover of negative interpersonal events to postsession insight and the role of
difficulties in emotion regulation in this spillover effect. METHOD: Participants
were 129 adolescents with moderate to severe depressive symptoms and suicidal
ideation (Mage = 14.96, 83% female, 56% African American/Black) participating in
a comparative efficacy trial of Attachment-Based Family Therapy (ABFT) and Family
Enhanced Nondirective Supportive Therapy (FE-NST). A within-subject mediation
model tested presession negative affect as a mediator of spillover of past week's
events on postsession insight. We then examined baseline difficulties in emotion
regulation (DERS) as a between-subjects moderator of the mediation model.
RESULTS: Negative affect partially mediated (44%) the spillover of the past
week's negative events on adolescents' ratings of postsession insight (p = .03,
95% confidence interval, CI [-.09., -.002]). Baseline DERS increased adolescents'
vulnerabilities to spillover effects (p = .01, 95% CI [-.28, -.03]). Negative
interpersonal events from the past week influence presession negative affect and
spill over to adolescents' abilities to gain insight from their treatment
sessions. Adolescents who began treatment with greater DERS were particularly
vulnerable to these spillover effects. Findings indicate the need for therapists
to adapt sessions to individual differences in depressed and suicidal
adolescents' exposure to negative interpersonal events preceding treatment and in
their vulnerabilities to spillover and emotion dysregulation. (PsycINFO Database
Record
PMID- 29939054
TI - Mothers' posttraumatic stress and child adjustment problems in families seeking
services for intimate partner violence.
AB - OBJECTIVE: This study examines whether fluctuation in mothers' posttraumatic
stress symptoms (PTSSs) predicts fluctuation in child adjustment problems in
families seeking services for intimate partner violence (IPV). METHOD:
Participants were 300 mothers (mean age = 30.65 years) of children (mean age =
6.88 years; 49% female) who were seeking shelter or legal services because of
IPV. Most mothers identified as Hispanic (57%), followed by Black/African
American (26%). Mothers reported PTSSs on a 7-item screening measure and reported
child externalizing and internalizing problems on the Child Behavior Checklist.
Mother and child functioning were assessed shortly after the mothers' requested
services and then every 4 months for a 5-year period. RESULTS: Eighty-one percent
of mothers reported clinical levels of PTSSs at the initial assessment. As
hypothesized, fluctuation in mothers' PTSSs predicted fluctuation in child
externalizing and internalizing problems during the ensuing 4-month period. These
relations, however, occurred within subjects but not between subjects. The within
subject associations emerged after accounting for IPV and mothers' depressive
symptoms and were stronger for older children than younger children. The strength
of the associations decreased over time. CONCLUSIONS: Addressing women's trauma
symptoms at the point of seeking services for IPV has possible implications for
child mental health. Attempting to reduce mothers' PTSSs may have positive
effects for women as well as their children. (PsycINFO Database Record
PMID- 29939055
TI - Measuring fear change within exposures: Functionally-defined habituation predicts
outcome in three randomized controlled trials for pediatric OCD.
AB - OBJECTIVE: This study measured a variety of within-exposure fear changes and
tested the relationship of each with treatment outcomes in exposure therapy.
METHOD: We coded 459 videotaped exposure tasks from 111 participants in 3
clinical trials for pediatric obsessive-compulsive disorder (OCD; POTS trials).
Within exposures, fear level was observed continuously and alongside exposure
process. Fear change metrics of interest were selected for relevance to
mechanistic theory. Fear decreases were classified by function; nonhabituation
decreases were associated with observed nonlearning processes (e.g., avoidance),
whereas habituation decreases appeared to result from an internal and indirect
process. Outcomes were posttreatment change in symptom severity, global
improvement, and treatment response. RESULTS: Greater cumulative habituation
across treatment was associated with larger reductions in symptom severity,
greater global improvement, and increased odds of treatment response. Fear
activation, fear variability, and nonhabituation fear decreases did not predict
any outcomes. Exploratory analyses examined fear changes during habituation and
nonhabituation exposures; higher peak fear during nonhabituation exposures was
associated with attenuated global improvement. CONCLUSIONS: Habituation is
conceptually consistent with multiple mechanistic theories and should continue to
be investigated as a practical marker of initial extinction learning and possible
moderator of the relationship between fear activation and outcome. Results
support the importance of functional and frequent fear measurement during
exposures, and discussion considers implications of these findings for future
studies aiming to understand learning during exposure and improve exposure
delivery. (PsycINFO Database Record
PMID- 29939056
TI - Cluster randomized trial of the classroom SCERTS intervention for elementary
students with autism spectrum disorder.
AB - OBJECTIVE: This cluster randomized trial (CRT) evaluated the efficacy of the
Classroom Social, Communication, Emotional Regulation, and Transactional Support
(SCERTS) Intervention (CSI) compared with usual school-based education with
autism training modules (ATM). METHOD: Sixty schools with 197 students with
autism spectrum disorder (ASD) in 129 classrooms were randomly assigned to CSI or
ATM. Mean student age was 6.79 years (SD 1.05) and 81.2% were male. CSI teachers
were trained on the model and provided coaching throughout the school year to
assist with implementation. A CRT, with students nested within general and
special education classrooms nested within schools, was used to evaluate student
outcomes. RESULTS: The CSI group showed significantly better outcomes than the
ATM group on observed measures of classroom active engagement with respect to
social interaction. The CSI group also had significantly better outcomes on
measures of adaptive communication, social skills, and executive functioning with
Cohen's d effect sizes ranging from 0.31 to 0.45. CONCLUSION: These findings
support the preliminary efficacy of CSI, a classroom-based, teacher-implemented
intervention for improving active engagement, adaptive communication, social
skills, executive functioning, and problem behavior within a heterogeneous sample
of students with ASD. This makes a significant contribution to the literature by
demonstrating efficacy of a classroom-based teacher-implemented intervention with
a heterogeneous group of students with ASD using both observed and reported
measures. (PsycINFO Database Record
PMID- 29939058
TI - Multivariate associations of ideal affect with clinical symptoms.
AB - Prior research has indicated that ideal affect (i.e., the affective states that
people value and would ideally like to experience) may be relevant to mental
health outcomes. Studies to date, however, have not used comprehensive
multivariate models that account for covariation among facets of ideal affect and
incorporate multiple clinical outcomes. In the present studies, we used
structural equation modeling to examine the multivariate effects of ideal affect
on symptoms of depression, anxiety, and alcohol abuse in 2 moderately large
samples of undergraduates (N = 293 and N = 146). Exploratory results of Study 1
indicated that valuation of high arousal positive affective states was
significantly associated with lower depression symptoms but higher anxiety and
alcohol abuse symptoms and that valuation of high arousal negative states was
specifically associated with greater anxiety symptoms. These results were shown
to be structurally invariant across samples and ethnicities in Study 2, which
also found that ideal-actual affect discrepancies were significantly associated
with symptoms of depression and anxiety. These findings support and extend the
hypothesis that ideal affect is implicated in clinical outcomes by highlighting
the importance of jointly considering multiple facets of ideal and actual affect
as they relate to a range of clinical syndromes. (PsycINFO Database Record
PMID- 29939057
TI - Cognition in older patients with multiple sclerosis compared to patients with
amnestic mild cognitive impairment and healthy older adults.
AB - OBJECTIVE: Progress in the treatment of multiple sclerosis (MS) has resulted in
larger numbers of patients living to an advanced age, but little is known about
the cognitive status of these individuals. The primary purpose of this study was
to identify differences in the cognitive performance between elderly individuals
with MS and those with amnestic mild cognitive impairment (aMCI). METHOD: Three
groups ranging in age from 60 to 80 were compared: patients with MS (n = 64),
patients with aMCI (n = 58), and healthy adults (n = 70). All participants
completed a standard neuropsychological test battery that evaluated domains of
attention, processing speed, executive function, memory, language, and visual
spatial function. RESULTS: Compared to age- and gender-matched healthy controls,
elderly MS patients exhibited a pattern of cognitive impairment centering on
information processing speed and memory that was consistent with the deficits
observed in other studies of MS patients regardless of age. Compared to aMCI
patients, the MS patients exhibited worse performance on measures of processing
speed, but better performance on a measure of memory under cued conditions
(Selective Reminding Test), a nonspeeded measure of language (Boston Naming
Test), and measures of executive function with processing speed statistically
controlled (Trail Making Test, Stroop Test). CONCLUSIONS: Differences on
neuropsychological measures can serve to distinguish aMCI from MS-related
cognitive impairment in older patients, but it is essential that these measures
control for the deficit in processing speed that is such a primary feature of MS.
(PsycINFO Database Record
PMID- 29939059
TI - Trait emotional intelligence, coping, and occupational distress among
resettlement workers.
AB - OBJECTIVE: Trait emotional intelligence has recently emerged as a negative
predictor of work-related distress. However, research that considers the
mechanisms underlying the relationship between trait emotional intelligence and
distress is lacking, in particular among workers with emotionally intensive
occupations. The purpose of this study was to analyze the mediating pathway of
coping behaviors in the relations between trait emotional intelligence, and work
related distress outcomes, namely secondary traumatic stress and job burnout in a
sample of refugee resettlement workers. METHOD: Participants were 210
resettlement workers from six organizations in the United States who completed a
questionnaire. Questions included self-reported measures of secondary traumatic
stress, burnout, trait emotional intelligence, coping behaviors, and history of
trauma. The majority of participants identified as White (64.9%) and female
(73.6%). The average participant was 32.96 years old (SD = 10.22) and was
employed in the same position for 2.64 years (SD = 4.67). RESULTS: Unhealthy
coping (e.g., substance use and denial), emerged as a significant mediator of the
relations between trait emotional intelligence and the outcomes, with 43% and 64%
of the total effects for secondary traumatic stress and burnout mediated.
Specifically, trait emotional intelligence negatively related to secondary
traumatic stress and burnout via a reduction in unhealthy coping behaviors,
rather than an increase in healthy coping ones. CONCLUSIONS: Training programs
promoting the psychological well-being of employees often focus on the promotion
of healthy coping practices. These results suggest the potential value of
including trait emotional intelligence training in the development of such
programs. (PsycINFO Database Record
PMID- 29939060
TI - Posttraumatic stress disorder symptoms improve after an integrated brief alcohol
intervention for OEF/OIF/OND veterans.
AB - OBJECTIVE: Although brief alcohol interventions (BAIs) that incorporate
personalized feedback demonstrate efficacy for reducing the frequency and
quantity of alcohol consumption in veteran samples, little research has explored
the influence of BAIs in reducing symptoms of posttraumatic stress disorder
(PTSD). The goal of this investigation was to understand whether PTSD symptom
severity and diagnostic status changed after exposure to an intervention that
targeted alcohol misuse and integrated feedback on PTSD. METHOD: Sixty-eight
combat veterans (8.8% female; 27.9% African American) who screened positive for
hazardous drinking were recruited from a Veterans Affairs Medical Center.
Participants received a 1-session brief intervention that primarily targeted
alcohol misuse but also included personalized feedback and psychoeducation on
PTSD symptoms and coping. Participants were randomized to receive personalized
written feedback either with or without a motivational interview. RESULTS: A
mixed-model repeated measures analysis revealed that PTSD symptom severity was
significantly lower at the 6-week (M = 41.47, SD = 28.94) and 6-month (M = 35.56
SD = 26.99) follow-up appointments relative to baseline (M = 51.22, SD = 26.67),
F(2, 127.24) = 38.32, p < .001. Regression analyses demonstrate that the percent
change in alcohol use was related to the change in PTSD severity. Further,
results indicated that a motivational-interviewing-style counseling session
accompanying the feedback was not significantly more efficacious than receiving
feedback only. CONCLUSION: A brief alcohol intervention that integrates
information on PTSD has the potential to reduce PTSD severity. Personalized
alcohol and PTSD feedback may be useful as an opportunistic intervention for
OEF/OIF veterans. (PsycINFO Database Record
PMID- 29939061
TI - A novel dissemination effort for prolonged exposure: Practice and dissemination
curriculum.
AB - OBJECTIVES: This study examines the effectiveness of a novel dissemination and
implementation curriculum for prolonged exposure (PE). Predoctoral clinical
psychology interns completed a sequential, four-part curriculum that culminated
in a community-based practicum during which interns conducted a PE workshop. We
hypothesized that workshop participants would report more favorable attitudes
regarding PE after completing the intern-led workshop than endorsed at the outset
of the workshop. METHOD: A total of 53 workshop participants attended and
completed questionnaires. The majority of workshop participants had a master's
level degree or educational specialist degree (n = 28; 57.1%) and were currently
a counselor or psychosocial rehabilitation worker (n = 21; 42.9%). We examined
changes between pre- and posttraining time points for five self-report items
related to negative attitudes toward PE and three self-report items related to
intent to use PE. RESULTS: There was a significant effect of workshop training on
four out of five items related to negative attitudes toward PE. The
nonsignificant result of the fifth item may be due to a ceiling effect given that
baseline scores for this item were very positive. There was a significant effect
of workshop training on all three items related to intent to use PE. CONCLUSIONS:
Results suggested that this sequential four-part curriculum may be an effective
way of combining education, training, and dissemination efforts. Future research
should examine if similar results can be achieved with a controlled research
design and whether outcomes would generalize to actual PE delivery skills in
routine clinical care. (PsycINFO Database Record
PMID- 29939062
TI - Defendant stereotypicality moderates the effect of confession evidence on
judgments of guilt.
AB - This research examined whether criminal stereotypes-i.e., beliefs about the
typical characteristics of crime perpetrators-influence mock jurors' judgments of
guilt in cases involving confession evidence. Mock jurors (N = 450) read a trial
transcript that manipulated whether a defendant's ethnicity was stereotypic or
counterstereotypic of a crime, and whether the defendant had confessed to the
crime or not. When a confession was present, the transcript varied whether the
confession had been obtained using high-pressure or low-pressure interrogation
tactics. Consistent with the hypothesis, the presence of a confession (relative
to no confession) increased perceptions of the defendant's guilt when the
defendant was stereotypic of the crime, regardless of the interrogation tactics
that had been used to obtain it. When the defendant was counterstereotypic of the
crime, however, the presence of a confession did not significantly increase
perceptions of guilt, even when the confession was obtained using low-pressure
interrogation tactics. These findings demonstrate the potentially powerful
effects of criminal stereotypes on legal judgments and suggest that individuals
who fit a criminal stereotype may be disadvantaged over the course of the
criminal justice process. (PsycINFO Database Record
PMID- 29939063
TI - Closing with emotion: The differential impact of male versus female attorneys
expressing anger in court.
AB - Emotion expression is a key part of trial advocacy. Attorneys are advised to gain
credibility with juries by demonstrating conviction through anger expression. In
3 experiments, we tested whether expressing anger in court makes attorneys more
effective and whether this depends on their gender. We randomly assigned
participants (n = 120 undergraduates) to view a male or female attorney
presenting the same closing argument in either a neutral or angry tone
(Experiment 1). They reported their impressions of the attorney and how likely
they would be to hire the attorney. People used the positive aspects of anger
(e.g., conviction, power), to justify hiring an angry male attorney. Yet, they
used the negative aspects of anger (e.g., shrill, obnoxious), to justify not
hiring a female attorney. We replicated this effect in Experiment 2 with a
community sample (n = 294). Experiment 3 (n = 273) demonstrated that the attorney
anger by gender interaction generalized to perceptions of effectiveness across a
set of additional attorney targets. Finally, a high-powered analysis collapsing
across experiments confirmed that when expressing anger relative to when calm,
female attorneys were seen as significantly less effective, while angry male
attorneys were seen as significantly more effective. Women might not be able to
harness the persuasive power of expressing anger in the courtroom, which might
prevent female attorneys from advancing in their careers. (PsycINFO Database
Record
PMID- 29939064
TI - Does anyone else look familiar? Influencing identification decisions by asking
witnesses to re-examine the lineup.
AB - Two experiments were conducted to see if asking witnesses to take another look at
the lineup after they voiced their identification decisions would alter their
choices, and if confirming feedback could then be used to solidify the selections
they shifted to. Participants watched a simulated crime and were asked to
identify the culprit from a photographic lineup. After voicing their
identification decisions, participants were prompted to re-examine the lineup.
Half of the participants then received confirming feedback for their decisions,
regardless of whether they shifted to a new picture or not. Later on, a different
experimenter escorted participants to a second room and administered the same
lineup again. In Experiment 1 (N = 432), biased instructions were used to
encourage choosing, and when participants were prompted to re-examine the lineup,
70% changed their identification decisions and selected a different picture. When
that new selection was reinforced with feedback and participants were given a
second opportunity to identify the culprit at a later time, 72% selected the
picture they shifted to as the culprit. Participants who made their decisions
more quickly were less likely to shift, but accuracy did not predict shifting.
This general pattern of findings was replicated using unbiased instructions in
Experiment 2 (N = 237). Results suggest that prompting witnesses to re-examine
the lineup can often lead witnesses to change their identification decisions, and
when the altered choice is reinforced, they will often stay with that influenced
decision over time, asserting it with a high degree of confidence. (PsycINFO
Database Record
PMID- 29939065
TI - Within-treatment change in antisocial attitudes and reoffending in a large sample
of custodial and community offenders.
AB - This study tested evidence for antisocial attitudes as a mechanism of change in
offender treatment by examining whether the Measures of Antisocial Attitudes and
Associates (MCAA) and within-treatment change in scores on this scale have
predictive validity for risk of reoffending. Pretreatment and posttreatment
scores on the MCAA were obtained from a large sample of 1,858 offenders who had
completed offender treatment programs while in custody (n = 854) or in the
community (n = 1,004). Individual within-treatment change was calculated with
simple difference scores as well as categorizations of clinically significant
change. Results showed that discrete scores on a number of MCAA measures were
associated with reoffending hazard at pretreatment and at posttreatment. Change
over treatment was also highly significant at the group level whereas a modest
proportion of offenders achieved clinically significant change. None of the
measures of within-treatment change were significantly associated with
reoffending, however. The results suggest that self-reported antisocial attitudes
may not be a valid indicator of causal mechanisms of treatment or change in
offenders' risk of reoffending as a result of completing treatment. (PsycINFO
Database Record
PMID- 29939066
TI - Interviewing witnesses: Eliciting coarse-grain information.
AB - Eyewitnesses to crimes sometimes report inaccurate fine-grain details but fail to
report accessible and potentially accurate coarse-grain details. We asked college
students and community members (aged 17 to 62 years) who viewed a video of a
simulated crime to answer interviewers' questions at coarse- and fine-grained
levels of detail and measured the quantity and accuracy of their responses. Three
experiments (overall N = 219) also (a) provided comparative data for participants
who were interviewed using the open-ended Self-Administered Interview (Gabbert,
Hope, & Fisher, 2009) or one of two "report everything" open-ended procedures,
(b) tested the efficacy of the procedure using both written and verbal
interviews, and (c) examined the generality of the findings across different
encoding stimuli which required variations in the types of cued recall questions
asked. Coarse-grain reporting seldom occurred under the free recall interview
conditions. Witnesses provided abundant coarse-grain details when required to
respond to probes about specific details (i.e., cued recall forced report
conditions)-without obvious cost to overall accuracy relative to accuracy of
similar detail reported under free recall conditions-regardless of whether they
responded on a written questionnaire or in a face-to-face individual interview.
These experiments suggest that a procedure that requires cued recall forced
reporting of coarse-grain detail may offer potential in certain investigative
situations as an adjunct to the widely recommended open-ended forensic
interviewing techniques. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29939067
TI - "A cross-language study of decontextualized vocabulary comprehension in
toddlerhood and kindergarten readiness": Correction to Friend et al. (2018).
AB - Reports an error in "A cross-language study of decontextualized vocabulary
comprehension in toddlerhood and kindergarten readiness" by Margaret Friend, Erin
Smolak, Yushuang Liu, Diane Poulin-Dubois and Pascal Zesiger (Developmental
Psychology, Advanced Online Publication, Apr 05, 2018, np). In the article, the
reference for Legacy, Zesiger, Friend, & Poulin-Dubois (2016) should be Legacy,
Zesiger, Friend, & Poulin-Dubois (2018). The correct reference for the article is
listed below: Legacy, J., Zesiger, P., Friend, M., & Poulin-Dubois, D. (2018).
Vocabulary size and speed of word recognition in very young French-English
bilinguals: A longitudinal study. Bilingualism: Language and Cognition, 21, 137
149. https://doi.org/10.1017/S1366728916000833. All versions of this article have
been corrected. (The following abstract of the original article appeared in
record 2018-13949-001.) Recent studies demonstrate that emerging literacy depends
on earlier language achievement. Importantly, most extant work focuses on parent
reported production prior to 30 months of age. Of interest is whether and how
directly assessed vocabulary comprehension in the 2nd year of life supports
vocabulary and kindergarten readiness in the 4th year. We first contrasted
orthogonal indices of parent-reported production and directly assessed vocabulary
comprehension and found that comprehension was a stronger predictor of child
outcomes. We then assessed prediction from vocabulary comprehension controlling
for maternal education, preschool attendance, and child sex. In 3 studies early,
decontextualized vocabulary comprehension emerged as a significant predictor of
4th year language and kindergarten readiness accounting for unique variance above
demographic control variables. Further we found that the effect of early
vocabulary on 4th year kindergarten readiness was not mediated by 4th year
vocabulary. This pattern of results emerged in English monolingual children (N =
48) and replicated in French monolingual (N = 58) and French-English bilingual
children (N = 34). Our findings suggest that early, decontextualized vocabulary
may provide a platform for the establishment of a conceptual system that supports
both later vocabulary and kindergarten readiness, including the acquisition of a
wide range of concepts including print and number. Differences between parent
reported and directly assessed vocabulary and the mechanisms by which
decontextualized vocabulary may contribute to conceptual development are
discussed. (PsycINFO Database Record
PMID- 29939068
TI - Detection of volatile organic compounds in exhaled breath to screen lung cancer:
a systematic review.
AB - To evaluate the clinical value of volatile organic compounds (VOCs) in exhaled
breath for lung cancer (LC) screening, a systematic review was performed.
Systematic search for studies about exhaled VOCs for LC screening was conducted
according to PRISMA. Thirty eight studies with 4873 participants met the criteria
for inclusion in this systematic review. Generally speaking, the results suggest
that exhaled VOCs have potential to screen LC and more studies are needed in the
future.
PMID- 29939069
TI - Rectal radiation dose-reduction techniques in prostate cancer: a focus on the
rectal spacer.
AB - Prostate cancer is the most common cancer in men. External beam radiotherapy by a
variety of methods is a standard treatment option with excellent disease control.
However, acute and late rectal side effects remain a limiting concern in
intensification of therapy in higher-risk patients and in efforts to reduce
treatment burden in others. A number of techniques have emerged that allow for
high-radiation dose delivery to the prostate with reduced risk of rectal
toxicity, including image-guided intensity-modulated radiation therapy,
endorectal balloons and various forms of rectal spacers. Image-guided radiation
therapy, either intensity-modulated radiation therapy or stereotactic ablative
radiation therapy, in conjunction with a rectal spacer, is an efficacious means
to reduce acute and long-term rectal toxicity.
PMID- 29939071
TI - Attending to the biopsychosocial approach in Australia's mental health agenda.
PMID- 29939070
TI - Supervisory board process: Evidence from French public hospitals.
AB - We mobilize theories of corporate governance and the theory of the social
psychology of decision-making small groups to understand the operational process
of the public hospital supervisory board. More precisely, we empirically test the
mediation relationship of the decision-making process (effort norms, use of
knowledge and skills, and conflict cognitive) between its structure (size, the
composition, and diversity) and the performance of its roles (strategy, control,
and service). A total of 320 questionnaires coming from members of the French
public hospital supervisory board were collected. The aggregation of these
individual answers generates a sample of 159 public hospital supervisory boards.
The results of the tests of the assumptions of the research model confirm the
fact that the structure of the supervisory board does not influence the
performance of its roles. However, supervisory board effort norms positively
affect the performance of its roles positively. Only effort norms and the use of
knowledge and the skills partially play the role of mediator between the
supervisory board structure and the performance of its roles. Practical and
theoretical implications are exposed in the discussion.
PMID- 29939072
TI - Serum heat shock protein 90alpha have an advantage in diagnosis of colorectal
cancer at early stage.
AB - AIM: We investigated HSP90alpha as screening biomarker for early colorectal
cancer (CRC). METHODS & RESULTS: Seventy-seven CRC patients and 78 healthy
controls were enrolled. Plasma HSP90alpha was significantly higher in CRC
patients than in healthy controls (p < 0.05). levels were higher in late (stages
III and IV) CRC than in early (stages I and II) CRC (p = 0.022). HSP90alpha
conferred an advantage in the diagnosis of early CRC. Combination of HSP90alpha
and carcinoembryonic antigen improved the diagnostic sensitivity (84.4%) and
specificity (89.5%) for CRC (area under the curve: 0.968); for early CRC, the
sensitivity was 82.5% and specificity was 89.5% (area under the curve: 0.955).
CONCLUSION: HSP90 is a potential biomarker for the diagnosis of early CRC.
PMID- 29939073
TI - Transcutaneous bone conductive implants in patients with conductive/mixed hearing
loss: audiological outcomes in noise condition.
AB - BACKGROUND: Recently, the use of transcutaneous bone conduction implants (BCIs)
has been increased. However, scarce data about BCI hearing recovery in noise
conditions have been reported. OBJECTIVES: To investigate the audiological
benefits obtained with transcutaneous BCI-Sophono Alpha System in noise
conditions. To evaluate post-implantation clinical outcomes and patient
satisfaction levels. MATERIALS AND METHODS: Fourteen patients suffering from
conductive or mixed hearing loss implanted with the Sophono Alpha System were
evaluated. Patients underwent physical examination, free-field pure-tone and
speech audiometry both in unaided and aided conditions. The matrix sentence test
was employed with fixed noise at 65 dB, and with a fluctuating primary signal, in
three different conditions of noise presentations (S0/N0, S0/Ncontra, S0/Nipsi).
RESULTS: Hearing gain, expressed as the difference between pre-implant AC and
post-implant SAS free field, was on average 26.7 dB. The unaided speech
recognition score in quiet conditions had a mean value of 64.6%, and improved
after SAS implantation, achieving mean values of 98.2%. SRT50 with the matrix
sentence test improved in all three conditions of noise presentation.
CONCLUSIONS: Sophono Alpha System devices represent a valid treatment option for
hearing rehabilitation of patients with conductive or mixed hearing loss. The
audiological results regarding hearing gain in noise conditions were good.
PMID- 29939074
TI - Comparative analysis of differentially expressed genes related to triglyceride
metabolism between intramuscular fat and abdominal fat in broilers.
AB - 1. Lipid metabolism is an indispensable process in an organism, though little is
known about the regulatory mechanisms of fat deposition in different types of
adipose tissues. 2. The differentially expressed genes related to triglyceride
(TG) metabolism between abdominal and intramuscular fat (IMF) of Beijing-You
chickens were investigated in this study. 3. TG content in abdominal fat (AF)
(349.7 mg/g) was significantly higher (P < 0.01) than in the breast and thigh
(12.3 mg/g and 24.8 mg/g, respectively). 4. Using Agilent chicken gene-expression
profiling in adipose tissues between AF and muscle (breast and thigh), certain
representative genes related to fatty acid metabolism, lipoprotein catabolism and
esterification reactions were significantly upregulated (P < 0.05 or P < 0.01).
5. Genes involved in fatty acid oxidation or carbohydrate utilisation were
significantly up- or downregulated (P < 0.05 or P < 0.01), including those
involved with highly enriched pathways of lipid metabolism (PPAR, Wnt pathway and
inositol phosphate metabolism), cell junctions (focal adhesion and regulation of
actin cytoskeleton) and muscle contraction. 6. Overall, higher TG levels were
observed in AF tissue than in adipose tissues of breast and thigh, which could be
regulated through gene expression of pathways related to lipid metabolism (PPAR,
Wnt pathway and inositol phosphate metabolism), cell junctions (focal adhesion
and regulation of actin cytoskeleton) and muscle contraction. These results
provide clues to understanding the molecular mechanisms of TG metabolism between
abdominal and IMF.
PMID- 29939075
TI - Short-term 2.1 GHz radiofrequency radiation treatment induces significant changes
on the auditory evoked potentials in adult rats.
AB - PURPOSE: There is a growing interest in the usage of radiofrequency radiation
(RF) as a noninvasive brain stimulation method. Previously reported data
demonstrated that RF exposure caused a change in brain oscillations. Therefore,
we aimed to investigate effects of RF on brain oscillation by measuring the
auditory response of different brain regions in rats. MATERIALS AND METHODS: Rats
were randomly divided into three groups (n = 12 per each group): Cage control
(C), sham rats (Sh), and rats exposed to 2.1 GHz RF for 2 h/day for 7 days. At
the end of the exposure, auditory evoked potentials (AEPs) were recorded at
different locations in rats. Latencies and amplitudes of AEPs, evoked power,
inter-trial phase synchronization, and auditory evoked gamma responses were
obtained in response to an auditory stimulus. Furthermore, TBARS levels and 4
HNE, GFAP, iNOS, and nNOS expressions were evaluated in all groups. RESULTS: Peak
to-peak amplitudes of AEPs were significantly higher in the RF group compared
with the Sh group. There is no significant difference in peak latencies of AEPs
between groups. Beside, evoked power, inter-trial phase synchronization, and
auditory evoked gamma responses were significantly higher in the RF group
compared with the Sh group. In addition, the RF group had significantly lower
TBARS and 4-HNE levels than the Sh group. There were no significant differences
between groups for GFAP, nNOS, and iNOS levels, and between the C and RF groups
for all parameters. CONCLUSIONS: Our present findings suggest that short-term RF
treatment under chosen experimental conditions have statistically significant
effect on neuronal networks of rats by probably reducing oxidative damage.
However, this effect must be further studied for possible noninvasive brain
stimulation.
PMID- 29939076
TI - Neuroprotective effect of epigallocatechin-3-gallate (EGCG) on radiation-induced
damage and apoptosis in the rat hippocampus.
AB - PURPOSE: This study investigated the potential neuroprotective effect of
epigallocatechin-3-gallate (EGCG) on radiation-induced cell death and damage in
the hippocampus. MATERIALS AND METHODS: Adult male Wister rats received oral
treatment with EGCG at doses of 2.5 and 5 mg/kg/d for 3 d before 4 Gy gamma
irradiation. RESULTS: The pretreatment of irradiated rats with EGCG significantly
ameliorated the increased plasma levels of homocysteine, amyloid beta, TNF-alpha
and IL-6 levels and the decrease of dopamine and serotonin. Pretreatment with
EGCG also significantly ameliorated the irradiation-induced increase in the 4-HNE
and protein carbonyl levels and the decreased antioxidants including glutathione
level, and the activities of glutathione peroxidase and glutathione reductase in
the hippocampus. EGCG treatment prior to radiation exposure protected against DNA
damage and apoptosis in the hippocampus. The increase in the levels of p53,
Cytochrome-c, Bax and caspases 3 and 9 in the hippocampus were significantly
ameliorated with a significant increase in Bcl-2. These changes were supported by
marked protection of the dentate gyrus that exhibited a similar histological
structure of the control animals. CONCLUSIONS: EGCG can attenuate the severity of
radiation-induced damage and cell death in hippocampus recommending polyphenols
as successful option for protecting against radiation-induced hippocampal damage.
PMID- 29939078
TI - Echocardiographic evaluation of paediatric athlete's heart.
PMID- 29939077
TI - The role of matricellular proteins and tissue stiffness in breast cancer: a
systematic review.
AB - Malignancies consist not only of cancerous and nonmalignant cells, but also of
additional elements, as extracellular matrix. The aim of this review is to
summarize meta-analyses, describing breast tissue stiffness and risk of breast
carcinoma (BC) assessing the potential relationship between matricellular
proteins (MPs) and survival. A systematic computer-based search of published
articles, according to PRISMA statement, was conducted through Ovid interface.
Mammographic density and tissue stiffness are associated with the risk of BC
development, suggesting that MPs may influence BC prognosis. No definitive
conclusions are available and additional researches are required to definitively
clarify the role of each MP, mammographic density and stiffness in BC development
and the mechanisms involved in the onset of this malignancy.
PMID- 29939079
TI - Low systolic blood pressure for predicting all-cause mortality in patients
hospitalised with heart failure: a systematic review and meta-analysis.
PMID- 29939080
TI - Home and office blood pressure measurements as determinants of kidney disease in
the general population: The Finn-Home Study.
PMID- 29939081
TI - Physical activity modifies the risk of atrial fibrillation in obese individuals:
The HUNT3 study.
AB - Background Atrial fibrillation is the most common heart rhythm disorder, and high
body mass index is a well-established risk factor for atrial fibrillation. The
objective of this study was to examine the associations of physical activity and
body mass index and risk of atrial fibrillation, and the modifying role of
physical activity on the association between body mass index and atrial
fibrillation. Design The design was a prospective cohort study. Methods This
study followed 43,602 men and women from the HUNT3 study in 2006-2008 until first
atrial fibrillation diagnosis or end of follow-up in 2015. Atrial fibrillation
diagnoses were collected from hospital registers and validated by medical
doctors. Cox proportional hazard regression analysis was performed to assess the
association between physical activity, body mass index and atrial fibrillation.
Results During a mean follow-up of 8.1 years (352,770 person-years), 1459 cases
of atrial fibrillation were detected (4.1 events per 1000 person-years).
Increasing levels of physical activity were associated with gradually lower risk
of atrial fibrillation ( p trend 0.069). Overweight and obesity were associated
with an 18% (hazard ratio 1.18, 95% confidence interval 1.03-1.35) and 59%
(hazard ratio 1.59, 95% confidence interval 1.37-1.84) increased risk of atrial
fibrillation, respectively. High levels of physical activity attenuated some of
the higher atrial fibrillation risk in obese individuals (hazard ratio 1.53, 95%
confidence interval 1.03-2.28 in active and 1.96, 95% confidence interval 1.44
2.67 in inactive) compared to normal weight active individuals. Conclusion
Overweight and obesity were associated with increased risk of atrial
fibrillation. Physical activity offsets some, but not all, atrial fibrillation
risk associated with obesity.
PMID- 29939082
TI - Novel multidisciplinary approaches in the management of metastatic epidural
spinal cord compression.
PMID- 29939083
TI - Avelumab: is it time to get excited?
PMID- 29939084
TI - Quantitative evaluation of the relative apparent diffusion coefficient values on
multiparametric magnetic resonance imaging to predict higher Gleason score
prostate cancer.
AB - INTRODUCTION: Apparent diffusion coefficient (ADC) values on multiparametric
magnetic resonance imaging (mpMRI) have been reported to correlate with high
Gleason score (GS) prostate cancer. However, the relative ADC values between
tumor lesions and normal tissue have been suggested as more suitable than the
absolute ADC values for evaluation of diffusion abnormalities, because absolute
ADC values are susceptible to differences in scanners or scanner settings. The
present study evaluated the usefulness of the relative assessment of ADC values
between tumor lesions and normal tissue on preoperative mpMRI for the prediction
of high-risk prostate cancer on radical prostatectomy specimens. MATERIALS AND
METHODS: A retrospective analysis of 48 men who underwent radical prostatectomy
between January 2013 and December 2014 was conducted. MpMRI was performed with a
3.0-T scanner using b-values of 0 and 1500 s/mm2. ADC values of the tumor
(ADCTUMOR) and normal prostate and the relative ADC tumor/normal ratio (ADCTNR)
were evaluated by two radiologists. RESULTS: The inter-rater reliability between
two radiologists for ADCTUMOR measurement was high, with Pearson's r = 0.982.
There was no difference in ADCTUMOR between GS <=7 and GS >=8. In contrast,
ADCTNR was significantly lower in GS >=8 than in GS <=7. ROC curves of ADCTNR to
predict higher GS (>=8) showed better classification performance (AUC = 0.8243, p
= .0012 by radiologist A and AUC = 0.7961, p = .0031 by radiologist B) than of
ADCTUMOR. CONCLUSIONS: The relative assessment of ADC values between tumor
lesions and normal tissue could improve the detection rate of high-risk prostate
cancers.
PMID- 29939086
TI - It is a problem and it is not a problem: Dilemmatic talk of the psychological
effects of female genital cutting.
AB - This qualitative study aimed to explore the psychological effects of female
genital cutting in the United Kingdom within a systemic psychological framework.
Semi-structured interviews were carried out with 13 women who had experienced
female genital cutting. Four key themes emerged from thematic analysis of the
data: (1) wholeness contested, (2) sexuality milestones and female genital
cutting awareness, (3) salvaging family relationships and (4) for our own good.
Findings highlight the importance of recognising the relational nature of how
women perceive the psychological effects of female genital cutting and how these
reactions are negotiated in their social sphere.
PMID- 29939085
TI - Post-exposure prophylaxis (PEP) for rabies with purified chick embryo cell
vaccine: a systematic literature review and meta-analysis.
AB - INTRODUCTION: Fifteen million people each year receive post-exposure prophylaxis
(PEP) to prevent rabies, yet the disease remains neglected and highly under
reported. Areas covered: In this systematic literature review, we assessed the
immunogenicity, efficacy, and safety of a purified chick embryo cell-culture
rabies vaccine (PCECV) for PEP against rabies by intramuscular (IM) or
intradermal (ID) administration. We performed meta-analyses to compare
immunogenicity according to the route of vaccine administration, study
population, and PEP regimen, such as number of doses, and concomitant rabies
immunoglobulin. Expert commentary: There were 54 estimates of immune responses to
vaccination, which showed that in the overall population, after starting PEP with
PCECV by the IM or ID route (>=2.5 IU per dose), almost all individuals had
rabies virus neutralizing antibody (RVNA) titers above the World Health
Organization (WHO) recommended serological threshold for an adequate immune
response to vaccination (RVNA >=0.5 IU/ml by day 14). In the overall population,
PCECV had an acceptable safety profile. However, given that there are 59,000
human rabies deaths reported annually, the challenge is to improve access to
PCECV for PEP against human rabies.
PMID- 29939087
TI - Absolute bioluminescence imaging at the single-cell level with a light signal at
the Attowatt level.
AB - Bioluminescence imaging (BLI) demonstrates cellular events as a light signal at
the single-cell level using a highly sensitive, cooled CCD camera. However, BLI
signals are relative values and thus, images taken on different days or using
different equipment cannot be compared directly. We established a reference LED
light source that was characteristic of the total flux and light distribution and
calibrated the BLI system as an absolute light signal. This calibrated BLI system
revealed that the average light signal of beetle luciferase was at an attowatt
level per sec at the single cell level.
PMID- 29939088
TI - A PAGE screening approach for identifying CRISPR-Cas9-induced mutations in
zebrafish.
AB - The introduction of CRISPR-Cas9 technology for targeted mutagenesis has
revolutionized reverse genetics and made genome editing a realistic option in
many model organisms. One of the difficulties with this technique is screening
for mutations in large numbers of samples. Many screening approaches for
identifying CRISPR-Cas9 mutants have been published; however, in practice these
methods are time consuming, expensive, or often yield false positives. This
report describes a PCR-based screening approach using non-denaturing PAGE. This
approach does not depend on the formation of heteroduplexes and reliably detects
changes as small as 1 base-pair (bp) in nucleic acid length at the target site.
This approach can be used to identify novel mutations and is also useful as a
routine genotyping method.
PMID- 29939089
TI - CRISPR/Cas9: the gold standard of genome editing?
PMID- 29939090
TI - A simple microfluidic device for live cell imaging of Arabidopsis cotyledons,
leaves, and seedlings.
AB - One of the challenges of performing live-cell imaging in plants is establishing a
system for securing the sample during imaging that allows for the rapid addition
of treatments. Here we report how a commercially available device called a
HybriWellTM can be repurposed to create an imaging chamber suitable for
Arabidopsis seedlings, cotyledons and leaves. Liquid in the imaging chamber can
be rapidly exchanged to introduce chemical treatments via microfluidic passive
pumping. When used in conjunction with fluorescent biosensors, this system can
facilitate live-cell imaging studies of signal transduction pathways triggered by
different treatments. As a demonstration, we show how the HybriWell can be used
to monitor flg22-induced calcium transients using the R-GECO1 calcium indicator
in detached Arabidopsis leaves.
PMID- 29939091
TI - A stainless-steel mortar, pestle and sleeve design for the efficient
fragmentation of ancient bone.
AB - Different types of milling equipment - such as oscillating ball mills, freezer
mills, mortar and pestle - can be used to fragment ancient bone prior to DNA
extraction. However, each of these tools is associated with practical drawbacks.
Here, we present the design for a stainless-steel mortar and pestle, with a
removable sleeve to contain bone material. The tool is easy to clean, practical
and its simplicity allows university workshops equipped with a lathe, boring
tools and a milling machine to make these components at local expense. This
design allows for the efficient fragmentation of ancient bone and improves sample
throughput. This design is recommended as a useful, economical addition to
existing laboratory equipment for the handling of ancient bone.
PMID- 29939092
TI - Thanking BioTechniques' advertisers for making print possible.
PMID- 29939093
TI - The flash-small-pool PCR: how to transform blotting and numerous hybridization
steps into a simple denatured PCR.
AB - Numerous human diseases are associated with abnormal expansion of unstable
trinucleotide repeats (TNRs). TNR instability mechanisms are complex, and remain
only partially understood. Small-pool-PCR (SP-PCR) is the reference method to
assess TNR instability. SP-PCR amplifies a low number of DNA molecules and is
followed by Southern blot. However, SP-PCR remains expensive and time consuming.
Here, we describe an optimized SP-PCR that can be done in a day, which reduces
cost and experimental biases: the flash-small-pool PCR (FSP-PCR). This method
consists of a fluorescent PCR on a few DNA molecules, followed by an alkaline gel
electrophoresis revealed with a near infra-red detector system. With reduced
experimental steps, cost, and time consumption, microsatellite analysis will
become more accessible due to FSP-PCR.
PMID- 29939094
TI - Determination of polyurethane-grafted peptide (GSGREDVGSG) using bicinchoninic
acid assay.
AB - The goal in the presented study was to develop a simple, fast and accurate method
for measuring the surface density of a short peptide sequence bound to a
polymeric substrate. We analyzed polyurethane samples chemically modified with
acrylic acid and polyurethane-grafted peptide (GSGREDVGSG) and investigated the
possibility of using the bicinchoninic acid (BCA) assay to determine surface
density of the solid-supported peptide. We set the conditions (temperature, time)
under which the test should be conducted. We also studied the interaction of the
BCA reagent with polyurethane substrate and the effect of drying conditions as
well as material type and form on the test response. We have proposed potential
factors that might interfere with the BCA assay and chosen the proper control
materials.
PMID- 29939095
TI - SEER study of ablation versus partial nephrectomy in cT1A renal cell carcinoma.
AB - AIM: Compare ablation versus partial nephrectomy (PN) in T1A renal cell carcinoma
(RCC) treatment, using the SEER database. METHODS: Patients with diagnosed T1A
RCC from 2004 to 2013 were identified. Propensity matching paired subjects with
similar background variables. Kaplan-Meier and Cox proportional hazards
regression were performed before and after matching. RESULTS: Cohort included
4592 patients (809 ablation, 3783 PN). PN compared with ablation group had
significantly increased overall survival (OS; 93.6% vs 81.9% 5-year survival; p <
0.0001) and cancer-specific survival (CSS; p < 0.0001). After matching (1222
pairs), PN group had significantly increased OS (91.0% vs 86.3% 5-year survival;
p = 0.0457) but similar CSS (p = 0.4023). CONCLUSION: Ablation offers similar CSS
but lower OS as PN for T1A RCC in this SEER database.
PMID- 29939096
TI - No food for thought: Food insecurity is related to poor mental health and lower
academic performance among students in California's public university system.
AB - This study examined the relationships between food insecurity, mental health, and
academic performance among college students in a California public university
system ( N = 8705). Structural equation modeling was performed to examine a
direct path from food insecurity to student grade point average and an indirect
path through mental health, controlling for demographic characteristics. Food
insecurity was related to lower student grade point average directly and
indirectly through poor mental health. These findings support the need for future
interventions and policy on the importance of providing students with the basic
needs to succeed both academically and in the future.
PMID- 29939097
TI - Reliability of pressure pain, vibration detection, and tactile detection
threshold measurements in lower extremities in subjects with knee osteoarthritis
and healthy controls.
AB - OBJECTIVES: Quantitative sensory testing (QST) is a method to assess
somatosensory function in osteoarthritis (OA), but reliability data on the
performance of different QST modalities on different joint structures are
missing. The main aims of our study were to assess intertester and intratester
reliability of tactile detection thresholds (TDTs), vibration detection
thresholds (VDTs), and pressure pain thresholds (PPTs) on different knee joint
structures. METHOD: In total, 32 subjects with knee OA and 32 volunteers with
healthy knees participated. TDTs, VDTs, and PPTs were examined on the medial
tibial condyle, medial tibiofemoral joint line, and rectus femoris muscle twice
on the first visit and once after 1-3 weeks. RESULTS: The intratester and
intertester intraclass correlation coefficients (ICCs) of PPT measurements varied
from 0.60 to 0.90 on different joint structures, showing good to excellent
reliability. Intratester reliability (ICC 0.64-0.76) of VDT measurements was
higher than intertester reliability (0.48-0.75). The intertester reliability of
TDT measurements was excellent in subjects with knee OA (ICC 0.84-0.86) and good
in controls (0.67) on the medial tibial condyle. Intratester reliability of TDT
measurements varied greatly. CONCLUSION: PPT testing is a reliable tool for
measuring pain thresholds on different joint structures. The VDT measurement is
reliable when taken by the same evaluator. The reliability of TDT measurements
depends on the site of the measurement.
PMID- 29939098
TI - Biomarker imprecision in precision medicine.
PMID- 29939099
TI - Combination effect of anti-rheumatic medications for coronary artery diseases
risk in rheumatoid arthritis: a nationwide population-based cohort study.
AB - OBJECTIVES: To determine whether a combination of anti-rheumatic drugs is
associated with the risk of coronary artery diseases (CAD) in incident rheumatoid
arthritis (RA) patients. METHODS: This population-based cohort study used
administrative data to identify 6260 newly-diagnosed patients with RA (age >=20
years) as the study group. The study end-point was occurrence of CAD according to
the ICD-9-CM codes. Exposure to different combinations of drugs and the risk of
CAD was assessed. These included different combinatiosn of celecoxib (Cx),
hydroxychloroquine (HCQ), methotrexate (MTX), and sulfasalazine (SSZ). Patients
who never used Cx, HCQ, MTX, or SSZ were used as a reference group. A Cox
proportional hazards model was used to estimate the hazard ratio (HR) of disease
after controlling for demographic and other co-morbidities. When the
proportionality assumption was violated, the spline curve of the Scaled
Schoenfeld residuals was fitted to demonstrate the estimated effect on CAD over
time for drug usage. RESULTS: Among RA patients, the adjusted HR (95% confidence
interval) of CAD for "Cx only", "Cx and HCQ ever", and "Cx, HCQ, MTX, and SSZ
ever", were 0.29 (0.19-0.44), 0.46 (0.24-0.88), and 0.42 (0.24- 0.75),
respectively, during the first period of 0-3, 4, or 7 years. However, they became
1.04 (0.78-1.38), 1.16 (0.62-2.19), and 0.59 (0.32-1.08), respectively, during
the second time period of 3, 4, or 7-10 years. The adjusted HR (95% CI) of CAD
for "Cx, MTX, and SSZ ever" remains constant at 0.12 (0.02-0.89). CONCLUSIONS:
Celecoxib-DMARDs drug combinations were associated with reduced CAD risk on
incident RA patients, and some of them exhibited the time-varying drug effect.
PMID- 29939100
TI - Identification of a complex population of chromatin-associated proteins in the
European sea bass (Dicentrarchus labrax) sperm.
AB - A very common conception about the function of the spermatozoon is that its
unique role is to transmit the paternal genome to the next generation. Most of
the sperm genome is known to be condensed in many species by protamines, which
are small and extremely positively charged proteins (50-70% arginine) with the
functions of streamlining the sperm cell and protecting its DNA. However, more
recently, it has been shown in mammals that 2-10% of its mature sperm chromatin
is also associated to a complex population of histones and chromatin-associated
proteins differentially distributed in the genome. These proteins are transferred
to the oocyte upon fertilization and may be involved in the epigenetic marking of
the paternal genome. However, little information is so far available on the
additional potential sperm chromatin proteins present in other protamine
containing non-mammalian vertebrates detected through high-throughput mass
spectrometry. Thus, we started the present work with the goal of characterizing
the mature sperm proteome of the European sea bass, with a particular focus on
the sperm chromatin, chosen as a representative of non-mammalian vertebrate
protamine-containing species. Proteins were isolated by acidic extraction from
purified sperm cells and from purified sperm nuclei, digested with trypsin, and
subsequently the peptides were separated using liquid chromatography and
identified through tandem mass spectrometry. A total of 296 proteins were
identified. Of interest, the presence of 94 histones and other chromatin
associated proteins was detected, in addition to the protamines. These results
provide phylogenetically strategic information, indicating that the coexistence
of histones, additional chromatin proteins, and protamines in sperm is not
exclusive of mammals, but is also present in other protamine-containing
vertebrates. Thus, it indicates that the epigenetic marking of the sperm
chromatin, first demonstrated in mammals, could be more fundamental and conserved
than previously thought. Abbreviations: AU-PAGE: acetic acid-urea polyacrylamide
gel electrophoresis; CPC: chromosomal passenger complex; DTT: dithiothreitol;
EGA: embryonic genome activation; FDR: false discovery rate; GO: Gene Ontology;
IAA: iodoacetamide; LC: liquid chromatography; LC-MS/MS: liquid chromatography
coupled to tandem mass spectrometry; MS: mass spectrometry; MS/MS: tandem mass
spectrometry; MW: molecular weight; PAGE: polyacrylamide gel electrophoresis;
PBS: phosphate buffered saline; SDS: sodium dodecyl sulfate; SDS-PAGE: sodium
dodecyl sulfate polyacrylamide gel electrophoresis; TCA: trichloroacetic acid.
PMID- 29939101
TI - Odors and incontinence: What does the nose know?
AB - The fear of producing malodors that can be detected by others is a daily cause of
anxiety for millions of people with incontinence. For many, the risk-whether real
or imagined-that leaked waste products will be detectable by odor is sufficiently
concerning to result in limitations on many types of activities. However, worry
about personal odors can sensitize our olfactory system and cause us to be more
aware of odors that may otherwise not be perceptible. In addition, heightened
olfactory attention can often lead to odor misattributions, such as when we
erroneously identify our body as the source of an odor that may simply be present
in the environment. Odors produced by our bodies (endogenous odors) do enjoy a
greater access to emotional brain centers and are processed faster than general
odors. Here we provide examples from both everyday life and laboratory studies to
explain how and why the olfactory system is unique among our sensory systems and
how this knowledge can provide insights to our concerns about smell and
incontinence and inform the development of products and solutions for
incontinence.
PMID- 29939103
TI - The impact of motives for Facebook use on Facebook addiction among ordinary users
in Jordan.
AB - BACKGROUND: Facebook has become the most popular social networking site with more
than 2.07 billion monthly active users. However, this popularity has its pains
too reflected by some addictive behavior among its users. Although researchers
have recently started to examine the factors that influence Facebook addiction,
little research examined the links between motives for Facebook use and Facebook
addiction. These studies mainly concentrate on students too. Also, little
research has explored this issue among general public in general and among people
in Jordan in particular. AIMS: This study therefore examined the impact of
motives for Facebook use on Facebook addiction among ordinary users in Jordan.
METHOD: A sample of 397 ordinary users is employed to achieve the study
objective. RESULTS: Results showed that 38.5% of the participants were addicted
to Facebook. Facebook addiction was significantly associated with six motives,
namely exhibitionism and companionship, entertainment, escapism and passing time,
social curiosity, relationships formation and relationships maintenance.
CONCLUSION: Among these six motives, escapism and passing time, exhibitionism and
companionship, and relationships maintenance were the strong predictors of
Facebook addiction.
PMID- 29939102
TI - Sequential treatment with riociguat and balloon pulmonary angioplasty for
patients with inoperable chronic thromboembolic pulmonary hypertension.
AB - Riociguat is the treatment of choice for inoperable patients with chronic
thromboembolic pulmonary hypertension (CTEPH). We addressed here whether
additional balloon pulmonary angioplasty (BPA) provides further benefits. A
prospective series of 36 consecutive patients with inoperable CTEPH were treated
with riociguat at least three months before BPA. All patients underwent
diagnostic workup at baseline, before BPA treatments, and six months after final
intervention. The main outcome measures were pulmonary hemodynamic parameters and
World Health Organization (WHO) functional class (FC). Significant improvements
in pulmonary hemodynamics and physical capacity were observed for riociguat
treatment, and subsequent BPA interventions yielded further benefits. With
targeted medication, WHO FC improved by at least one class in 13 (36.1%) patients
( P = 0.01). Hemodynamic assessment showed significant improvements in mean
pulmonary arterial pressure (mPAP) (49 +/- 12 mmHg vs. 43 +/- 12 mmHg; P = 0.003)
and PVR (956 +/- 501 dyn.s.cm-5 vs. 517 +/- 279 dyn.s.cm-5; P = 0.0001).
Treatment with a combination of targeted medication and BPA resulted in WHO FC
improvement in 34 (94.4%) patients. Hemodynamic assessment showed significant
improvement in mPAP (43 +/- 12 mmHg vs. 34 +/- 14 mmHg; P = 0.0001) and PVR (517
+/- 279 dyn.s.cm-5 vs. 360 +/- 175 dyn.s.cm-5; P = 0.0001). These findings
provide, for the first time, support for the therapeutic strategy recommended by
current guidelines.
PMID- 29939104
TI - Effects of prolonged paradoxical sleep deprivation with or without acute cold
stress on hemodynamic perturbations in rats.
AB - Prolonged paradoxical sleep deprivation (PSD) and cold stress (CS) are known to
cause sympathoexcitation and increase the risk of cardiovascular disease. The
present study examined the effect of PSD with CS on hemodynamic perturbations by
investigating blood pressure and heart rate variability (BPV and HRV) in
conscious rats. Adult male Sprague-Dawley rats were divided into three groups (n
= 10, each): normal sleep (NS), PSD of 72 h, and recovery sleep of 7 days after
PSD. When compared with NS, PSD increased systolic blood pressure in all three
conditions: before CS (PreCS), CS, and after CS (PostCS). The PSD also increased
heart rate in both PreCS and PostCS. Furthermore, spectral power changes were
observed throughout the experiment. The PSD increased very-low-frequency BPV in
PreCS, decreased very-low-frequency HRV in CS, and increased low-frequency BPV in
all three conditions. The PSD increased low-frequency HRV in PreCS, increased
high-frequency BPV in both CS and PostCS, and also increased high-frequency HRV
in both PreCS and CS but decreased that in PostCS. On the other hand, when
compared with PSD, recovery sleep has reversed most cardiovascular changes in PSD
toward the NS level. However, when compared with NS, spectral powers of very-low
frequency BPV in the recovery phase showed a lower level. These results showed
that in the resting condition, PSD might evoke sympathoexcitation with a tendency
to increase both very-low-frequency BPV and very-low-frequency HRV, as the
intensified myogenic oscillations. However, in the CS condition, PSD evoked the
sympathoexcitation yet might attenuate such myogenic oscillations.
PMID- 29939105
TI - Bridging the Great Divide: What Can Neurology Learn From Psychiatry?
AB - Neurology and psychiatry share common historical origins and rely on similar
tools to study brain disorders. Yet the practical integration of medical and
scientific approaches across these clinical neurosciences remains elusive.
Although much has been written about the need to incorporate emerging systems
level, cellular-molecular, and genetic-epigenetic advances into a science of mind
for psychiatric disorders, less attention has been given to applying clinical
neuroscience principles to conceptualize neurologic conditions with an integrated
neurobio-psycho-social approach. In this perspective article, the authors briefly
outline the historically interwoven and complicated relationship between
neurology and psychiatry. Through a series of vignettes, the authors then
illustrate how some traditional psychiatric conditions are being reconceptualized
in part as disorders of neurodevelopment and awareness. They emphasize the
intersection of neurology and psychiatry by highlighting conditions that cut
across traditional diagnostic boundaries. The authors argue that the divide
between neurology and psychiatry can be narrowed by moving from lesion-based
toward circuit-based understandings of neuropsychiatric disorders, from
unidirectional toward bidirectional models of brain-behavior relationships, from
exclusive reliance on categorical diagnoses toward transdiagnostic dimensional
perspectives, and from silo-based research and treatments toward
interdisciplinary approaches. The time is ripe for neurologists and psychiatrists
to implement an integrated clinical neuroscience approach to the assessment and
management of brain disorders. The subspecialty of behavioral neurology &
neuropsychiatry is poised to lead the next generation of clinicians to merge
brain science with psychological and social-cultural factors. These efforts will
catalyze translational research, revitalize training programs, and advance the
development of impactful patient-centered treatments.
PMID- 29939106
TI - Epidemiology and Natural History of Psychiatric Disorders After TBI.
AB - This article outlines the epidemiology of psychiatric disorders in individuals
with traumatic brain injury (TBI), with a focus on DSM axis I disorders diagnosed
on the basis of structured clinical interview. The epidemiology of psychiatric
disorders in the general population is described as a basis for understanding the
disorders that occur before and after TBI. For each disorder category, including
mood disorders, anxiety disorders, acute stress disorder, posttraumatic stress
disorder (PTSD), substance use disorders, psychotic disorders, eating disorders,
somatoform disorders, and adjustment disorders, the evidence from retrospective,
cross-sectional and prospective studies is reviewed, showing the frequency, time
course, and predictors of the disorders. Studies show elevated rates of
depressive and anxiety disorders after TBI, most commonly major depressive
disorder and PTSD, usually emerging in the first year postinjury but with delayed
onset in severe injury cases. Although individuals with a preinjury history are
more likely to develop these disorders, the nature of the disorders may change
after injury, and novel psychiatric disorders are also common. Even though the
frequency of anxiety disorders diminishes over the years postinjury, depressive
disorders are more persistent during postinjury years. Substance use-while high
before injury-declines after injury. The frequency of psychotic, eating,
somatoform, and adjustment disorders do not exceed population rates.
PMID- 29939107
TI - Assessing the predictive value of a neuropsychological model on concurrent
function in acute stroke recovery and rehabilitation.
AB - OBJECTIVE: Few studies have examined the relationship between cognition and
function for acute stroke inpatients utilizing comprehensive methods. This study
aimed to assess the relationship of a neuropsychological model, above and beyond
a baseline model, with concurrent functional status across multiple domains in
the early weeks of stroke recovery and rehabilitation. METHOD: Seventy-four acute
stroke patients were administered a comprehensive neuropsychological assessment.
Functional domains of ability, adjustment, and participation were assessed using
the Mayo-Portland Adaptability Inventory - 4 (MPAI-4). Hierarchical linear
regression was used to assess a neuropsychological model comprised of cognitive
tests scores on domains of executive function, memory, and visuospatial
constructional skills (VSC), after accounting for a baseline model comprised of
common demographic and stroke variants used to predict outcome. RESULTS: The
neuropsychological model was significantly associated, above and beyond the
baseline model, with MPAI-4 Ability, Participation, and Total scores (all p
values < .05). The strength of association varied across functional domains.
Analyzing tests of executive function, the Color Trails Test-Part 2 predicted
MPAI-4 Participation (beta = -.46, p = .001), and Total score (beta = -.32, p =
.02). CONCLUSION: Neuropsychological assessment contributes independently to the
determination of multiple domains of functional function, above and beyond common
medical variants of stroke, in the early weeks of recovery and rehabilitation.
Multiple tests of executive function are recommended to develop a greater
appreciation of a patient's concurrent functional abilities.
PMID- 29939108
TI - Investigations on fine fraction of aged municipal solid waste recovered through
landfill mining: Case study of three dumpsites from India.
AB - Reclamation of the dumps/landfills having huge quantities of decades-old garbage
(aged waste or legacy waste) in an environmentally sound manner is one of the
major challenges faced by the developing nations in general and in particular by
urban local bodies in India. The article presents the feasibility of landfill
mining operation specifically to recover soil-like material at old dumpsites of
India for re-use in geotechnical applications. Aged municipal solid waste was
collected from three dumpsites of India and initial tests were conducted on the
soil-like material of the municipal solid waste. Initial tests results of grain
size distribution, compositional analysis, organic content, total dissolved
solids, elemental analysis, heavy metal analysis and colour of the leached water
from finer fraction of aged municipal solid waste are presented. From the
preliminary investigation, it was found that organic content in 15-20-year-old
dumpsites varies between 5%-12%. The total dissolved solids ranges between 1.2%
1.5%. The dark coloured water leaching out from aged waste, with reference to
local soil, is one of the objectionable parameters and depends on the organic
content. The concentration of heavy metals of the finer fraction were compared
with the standards. It was found that copper, chromium and cadmium are present at
elevated levels in all the three dumpsites. The study concluded that the bulk of
the soil-like material from aged municipal solid waste landfills can be used as
cover material for landfills at the same site. However, some treatment in terms
of washing, thermal treatment, blending with local soil, biological treatment,
etc., is required before it can be re-used in other geotechnical applications.
PMID- 29939109
TI - Efficiency improvement by navigated safety inspection involving visual clutter
based on the random search model.
AB - Navigated inspection seeks to improve hazard identification (HI) accuracy. With a
tight inspection schedule, HI also requires efficiency. However, lacking
quantification of HI efficiency, navigated inspection strategies cannot be
comprehensively assessed. This work aims to determine inspection efficiency in
navigated safety inspection, controlling for HI accuracy. Based on a cognitive
method of the random search model (RSM), an experiment was conducted to observe
the HI efficiency in navigation, for a variety of visual clutter (VC) scenarios,
while using eye-tracking devices to record the search process and analyze the
search performance. The results show that the RSM is an appropriate instrument,
and VC serves as a hazard classifier for navigation inspection in improving
inspection efficiency. This suggests a new and effective solution for addressing
the low accuracy and efficiency of manual inspection through navigated inspection
involving VC and the RSM. It also provides insights into the inspectors' safety
inspection ability.
PMID- 29939110
TI - Progressive flaccid paraparesis with albuminocytologic dissociation: It's not
always Gullain-Barre syndrome.
AB - CONTEXT: Spondylodiscitis, or vertebral osteomyelitis, is an unusual infection of
the vertebral bodies and intervertebral discs that can occasionally present with
neurological signs. FINDINGS: We present a patient with subacute flaccid
paraparesis with associated albuminocytologic dissociation who was eventually
diagnosed with spondylodiscitis. CONCLUSION: The case presented depicts a
diagnostic difficulty encountered in clinical practice: Albuminocytologic
dissociation in CSF is not always attributed to Guillain-Barre syndrome and other
possible causes such as obstructive spinal cord lesions must always be
considered.
PMID- 29939111
TI - Peter Singer's Ethics: A Critical Appraisal.
PMID- 29939112
TI - Potential industrial utilization of pre-treated municipal solid waste
incineration fly ash.
AB - This study sought to establish the effectiveness of water washing pre-treatment
on the quality of municipal solid waste incineration (MSWI) fly ash (FA) for
reuse and solidification or stabilization (S/S). Initial analysis of the FA
sample shows that it did not meet the USEPA-1311 toxicity characteristic leaching
procedure (TCLP) regulatory limits of 2011. As a result, a two-stage water
washing process was carried out an attempt to improve the quality of the MSWI FA.
After the washing pre-treatment, the heavy metals in the FA sample met the
regulatory limits, thereby making it non-toxic for reuse or safe disposal. The
leachate from the washing process also passed regulatory standards of China (GB
8978 - 1996) and the 2011 USEPA-1311. The washing process successfully removed
more than 98% of each heavy metal under study. The process was excellent at
removing cadmium (99.99%) and very good at removing the rest of the heavy metals.
The 28-day compressive strength increased as the quantity of FA decreased. Also,
all the heavy metals in the samples prepared with the pre-treated FA met the
USEPA-1311 TCLP regulatory limit for reuse and safe disposal. The heavy metals
leachability and compressive strength tests showed that the effect of cement
based S/S was largely influenced by its quantity in the samples. The highest
compressive strength was attained by using 55% of the FA as replacement for
cement. However, FA replacements of up 70% also yielded good results that met the
1989 USEPA standard of 0.34 MPa (50 psi).
PMID- 29939115
TI - Peer-Reviewed SymposiaAn F denotes Fellow status in SHAPE America as of December
2017.
PMID- 29939118
TI - Peer-Reviewed Symposia: Part IIAn F denotes Fellow status in SHAPE America as of
December 2017.
PMID- 29939119
TI - Laypeople roles at road traffic crash scenes: a systematic review.
AB - This study aimed to identify the roles of laypeople at road traffic injuries
(RTIs). A systematic review was conducted according to the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The key words
of 'laypeople', 'layman', 'layperson', 'bystander', 'first responder', 'lay first
responder', 'road traffic', 'road traffic injury', 'crash injury', 'crash scene',
'emergency', 'trauma care', and 'prehospital trauma care' were used in
combination with the Boolean operators OR and AND. We did electronic search on
Google Scholar, PubMed, ISI Web of Science, CINAHL, Science Direct, Scopus,
ProQuest. Based on the reviewed studies, some factors such as cultural
conditions, knowledge, relief agencies, and demographic factors affect the
interventions of laypeople at the crash scene in functional areas. Regarding the
permanent presence of people at the crash scene, the present study can provide an
opportunity to reduce different side effects of RTIs imposed on the society.
PMID- 29939120
TI - Polynucleobacter hirudinilacicola sp. nov. and Polynucleobacter campilacus sp.
nov., both isolated from freshwater systems.
AB - Strains MWH-EgelM1-30-B4T and MWH-Feld-100T were isolated from the water columns
of two freshwater systems. Both strains represent delicate bacteria not easy to
work with in laboratory experiments. Phylogenetic analyses of the 16S rRNA genes
suggested that both strains were affiliated with the genus Polynucleobacter. Both
strains share 16S rRNA gene sequence similarities of >99 % with eight free-living
Polynucleobacter type strains, all affiliated with the cryptic species complex
PnecC. The full-length 16S rRNA gene sequences of the two strains differ only in
two and three positions, respectively, from the sequence of the closest related
Polynucleobacter type strain. Genome sequencing of both strains revealed
relatively small genome sizes of 2.0 Mbp and G+C contents of 45 mol%.
Phylogenetic analyses based on nucleotide sequences of 319 shared protein
encoding genes consistently placed the two strains in taxon PnecC but did not
suggest an affiliation with one of the previously described species. Pairwise
analyses of whole genome average nucleotide identities (gANI) with
representatives of all previously described Polynucleobacter species resulted in
both cases throughout in values <80 %. Pairwise comparison of the genomes of the
two new strains resulted in gANI values of 83.3 %. All gANI analyses clearly
suggested that strains MWH-EgelM1-30-B4T and MWH-Feld-100T represent two novel
Polynucleobacter species. We propose for these novel species the names
Polynucleobacter hirudinilacicola sp. nov. and Polynucleobacter campilacus sp.
nov. and strains MWH-EgelM1-30-B4T (=DSM 23911T=LMG 30144T) and MWH-Feld-100T
(=DSM 24007T=LMG 29705T) as the type strains, respectively.
PMID- 29939121
TI - Actinophytocola glycyrrhizae sp. nov. isolated from the rhizosphere of
Glycyrrhiza inflata.
AB - A Gram-stain-positive, aerobic actinomycete, designated strain BMP B8152T, was
isolated from the rhizosphere of Glycyrrhiza inflata collected ashore, in Kashi,
Xinjiang province, northwest PR China. A polyphasic approach was used to
establish the taxonomic position of this strain. BMP B8152T was observed to form
non-fragmented substrate mycelium, and relatively scanty aerial mycelium with rod
shaped spores. Cell-wall hydrolysates contained meso-diaminopimelic acid,
galactose, arabinose, glucose and rhamnose (trace). Mycolic acids were not
detected. The diagnostic phospholipids were identified as diphosphatidylglycerol,
phosphatidylethanolamine, hydroxyphosphatidylethanolamine, ninhydrin-positive
phosphoglycolipid and phosphatidylinositol. The predominant menaquinone and fatty
acid were MK-9(H4) and iso-branched hexadecanoate (iso-C16 : 0), respectively.
The phylogenetic analyses based on the 16S rRNA gene sequences indicated that BMP
B8152T formed a distinct monophyletic clade clustered with Actinophytocola
timorensisID05-A0653T (98.8 % 16S rRNA gene sequence similarity), Actinophytocola
oryzaeGMKU 367T (98.6 %), Actinophytocola corallinaID06-A0464T (98.2 %) and
Actinophytocola burenkhanensisMN08-A0203T (97.5 %). In addition, DNA-DNA
hybridization values between BMP B8152T and A. timorensisID05-A0653T(44.2+/-3.6
%) and A. oryzaeGMKU 367T(36.7+/-2.3 %) were well below the 70 % limit for
species identification. The combined phenotypic and genotypic data indicate that
the isolate represents a novel species of the genus Actinophytocola, for which
the name Actinophytocola glycyrrhizae sp. nov., is proposed, with the type strain
BMP B8152T (=KCTC 49002T=CGMCC 4.7433T).
PMID- 29939122
TI - Solimicrobium silvestre gen. nov., sp. nov., isolated from alpine forest soil.
AB - A Gram-stain-negative, rod-shaped, motile, catalase and cytochrome c oxidase
positive bacterial strain, designated S20-91T, was isolated from alpine forest
soil. Growth occurred within a temperature range of 0-25 degrees C. Yeast
extract was required for growth. Phylogenetic analysis based on 16S rRNA gene
sequencing showed that strain S20-91T was related to the genus Herminiimonas and
had the highest 16S rRNA gene sequence similarity to Herminiimonas arsenicoxydans
ULPAs1T (96.5 %). The strain contained ubiquinone 8 as the predominant
respiratory quinone and phosphatidylethanolamine, phosphatidylglycerol and
diphosphatidylglycerol as the major polar lipids. The major cellular fatty acids
(>10 %) were C16 : 1omega7c (55.3 %) and C16 : 0 (25.6 %). The genomic DNA G+C
content was 47.6 mol%. Combined data of genomic, phylogenetic, phenotypic and
chemotaxonomic analyses demonstrated that strain S20-91T represents a novel genus
and species, for which the name Solimicrobium silvestre gen. nov., sp. nov. is
proposed. The type strain is S20-91T (=DSM 104733T=LMG 30010).
PMID- 29939123
TI - Identification and characterization of novel mosquito-borne (Kammavanpettai
virus) and tick-borne (Wad Medani) reoviruses isolated in India.
AB - In 1954, a virus named Wad Medani virus (WMV) was isolated from Hyalomma
marginatum ticks from Maharashtra State, India. In 1963, another virus was
isolated from Sturnia pagodarum birds in Tamil Nadu, India, and named
Kammavanpettai virus (KVPTV) based on the site of its isolation. Originally these
virus isolates could not be identified with conventional methods. Here we
describe next-generation sequencing studies leading to the determination of their
complete genome sequences, and identification of both virus isolates as
orbiviruses (family Reoviridae). Sequencing data showed that KVPTV has an AT-rich
genome, whereas the genome of WMV is GC-rich. The size of the KVPTV genome is 18
234 nucleotides encoding proteins ranging 238-1290 amino acids (aa) in length.
Similarly, the size of the WMV genome is 16 941 nucleotides encoding proteins
ranging 214-1305 amino acids in length. Phylogenetic analysis of the VP1 gene,
along with the capsid genes VP5 and VP7, revealed that KVPTV is likely a novel
mosquito-borne virus and WMV is a tick-borne orbivirus. This study focuses on the
phylogenetic comparison of these newly identified orbiviruses with mosquito-,
tick- and Culicoides-borne orbiviruses isolated in India and other countries.
PMID- 29939125
TI - How myeloid cells contribute to the pathogenesis of prominent emerging zoonotic
diseases.
AB - Up to 75 % of emerging human diseases are zoonoses, spread from animals to
humans. Although bacteria, fungi and parasites can be causative agents, the
majority of zoonotic infections are caused by viral pathogens. During the past 20
years many factors have converged to cause a dramatic resurgence or emergence of
zoonotic diseases. Some of these factors include demographics, social changes,
urban sprawl, changes in agricultural practices and global climate changes. In
the period between 2014-2017 zoonotic viruses including ebola virus (EBOV),
chikungunya virus (CHIKV), dengue virus (DENV) and zika virus (ZIKV), caused
prominent outbreaks resulting in significant public health and economic burdens,
especially in developing areas where these diseases are most prevalent. When a
viral pathogen invades a new human host, it is the innate immune system that
serves as the first line of defence. Myeloid cells are especially important to
help fight viral infections, including those of zoonotic origins. However,
viruses such as EBOV, CHIKV, DENV and ZIKV have evolved mechanisms that allow
circumvention of the host's innate immune response, avoiding eradication and
leading to severe clinical disease. Herein, the importance of myeloid cells in
host defence is discussed and the mechanisms by which these viruses exploit
myeloid cells are highlighted. The insights provided in this review will be
invaluable for future studies looking to identify potential therapeutic targets
towards the treatment of these emerging diseases.
PMID- 29939124
TI - Mycobacterium shigaense sp. nov., a slow-growing, scotochromogenic species, is a
member of the Mycobacterium simiae complex.
AB - Among non-tuberculous mycobacteria (NTM), the Mycobacterium simiae complex is one
of the largest groups, consisting of 18 species of slow-growing mycobacteria. In
2009, a case of NTM-associated infectious skin disease was reported in Shiga
Prefecture, Japan. The patient presented with scattered nodules on the chest,
back and extremities, and an M. simiae-like organism was isolated from skin
biopsy specimens obtained from one of these lesions. Based on several
assessments, including multiple-gene analyses, biochemical characterization and
drug susceptibility testing, we concluded that this isolate represented a novel
species of NTM, and proposed the name 'Mycobacterium shigaense'. Since 2009, five
more cases of NTM-associated infectious disease in which there was a suspected
involvement of 'M. shigaense' have been reported. Interestingly, four of these
six cases occurred in Shiga Prefecture. Here we performed multiple-gene
phylogenetic analyses, physiological and biochemical characterization tests, drug
susceptibility tests, and profiling of proteins, fatty acids and mycolic acids of
eight clinical isolates from the six suspected 'M. shigaense' cases. The results
confirmed that all of the clinical isolates were 'M. shigaense', a slow-growing,
scotochromogenic species. Here M. shigaense is validly proposed as a new member
of the M. simiae complex, with the type strain being UN-152T (=JCM 32072T=DSM
46748T).
PMID- 29939126
TI - Simplicispira suum sp. nov., isolated from a dust collector at a pig farm.
AB - A novel Gram-stain-negative, strictly aerobic, polar-flagellated and rod-shaped
bacterium, designated SC1-8T, was isolated from a dust collector at a pig farm
located in Wanju-gun, Jeollabuk-do, Republic of Korea. The strain grew within a
temperature range of 4-37 degrees C (optimum, 28-30 degrees C), at pH 7.0-9.0
(pH 7.0-8.0) and with 0-2 % (w/v) NaCl (0 %). Colonies were white-beige, circular
and convex after 4 days of incubation on Reasoner's 2A agar. Based on the 16S
rRNA gene sequence analysis, strain SC1-8T was a member of the genus
Simplicispira, revealing the highest sequence similarities to Simplicispira limi
EMB325T (97.9 %), Simplicispira psychrophila DSM 11588T (97.4 %), Acidovorax
defluvii BSB411T (97.3 %), Simplicispira piscis RSG39T (97.1 %) and Simplicispira
metamorpha DSM 1837T (97.0 %). The predominant respiratory quinone was Q-8. The
polar lipids were phosphatidylethanolamone, diphosphatidylglycerol and
phosphatidylglycerol. The major fatty acids (>10 % of the total fatty acids) were
composed of C16 : 0 and summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c).
The DNA G+C content was 63.3 mol%. On the basis of phenotypic, genotypic and
phylogenetic evidence, strain SC1-8T is presented as a novel species, for which
the name Simplicispira suum sp. nov. is proposed. The type strain is SC1-8T
(=KACC 19329T=NBRC 113111T).
PMID- 29939128
TI - Viruses of invasive Argentine ants from the European Main supercolony:
characterization, interactions and evolution.
AB - The Argentine ant (Linepithema humile) is a highly invasive pest, yet very little
is known about its viruses. We analysed individual RNA-sequencing data from 48
Argentine ant queens to identify and characterisze their viruses. We discovered
eight complete RNA virus genomes - all from different virus families - and one
putative partial entomopoxvirus genome. Seven of the nine virus sequences were
found from ant samples spanning 7 years, suggesting that these viruses may cause
long-term infections within the super-colony. Although all nine viruses
successfully infect Argentine ants, they have very different characteristics,
such as genome organization, prevalence, loads, activation frequencies and rates
of evolution. The eight RNA viruses constituted in total 23 different virus
combinations which, based on statistical analysis, were non-random, suggesting
that virus compatibility is a factor in infections. We also searched for virus
sequences from New Zealand and Californian Argentine ant RNA-sequencing data and
discovered that many of the viruses are found on different continents, yet some
viruses are prevalent only in certain colonies. The viral loads described here
most probably present a normal asymptomatic level of infection; nevertheless,
detailed knowledge of Argentine ant viruses may enable the design of viral
biocontrol methods against this pest.
PMID- 29939127
TI - Cell-wall dyes interfere with Cryptococcus neoformans melanin deposition.
AB - Melanization is an intrinsic characteristic of many fungal species, but details
of this process are poorly understood because melanins are notoriously difficult
pigments to study. While studying the binding of cell-wall dyes, Eosin Y or
Uvitex, to melanized and non-melanized Cryptococcus neoformans cells we noted
that melanization leads to reduced fluorescence intensity, suggesting that
melanin interfered with dye binding to the cell wall. The growth of C. neoformans
in melanizing conditions with either of the cell-wall dyes resulted in an
increase in supernatant-associated melanin, consistent with blockage of melanin
attachment to the cell wall. This effect provided the opportunity to characterize
melanin released into culture supernatants. Released melanin particles appeared
mostly as networked structures having dimensions consistent with previously
described extracellular vesicles. Hence, dye binding to the cell wall created
conditions that resembled the 'leaky melanin' phenotype described for certain
cell-wall mutants. In agreement with earlier studies on fungal melanins
biosynthesis, our observations are supportive of a model whereby C. neoformans
melanization proceeds by the attachment of melanin nanoparticles to the cell wall
through chitin, chitosan, and various glucans.
PMID- 29939129
TI - Bactericidal efficacy of molybdenum oxide nanoparticles against antimicrobial
resistant pathogens.
AB - Multidrug-resistant bacteria pose a major threat to effective antibiotics and
alternatives to fight multidrug-resistant pathogens are needed. We synthetized
molybdenum oxide (MoO3) nanoparticles (NP) and determined their antibacterial
activity against 39 isolates: (i) eight Staphylococcus aureus, including
representatives of methicillin-resistant S. aureus epidemic clones; (ii) six
enterococci, including vancomycin-resistant isolates; and (iii) 25 Gram-negative
isolates (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa,
Acinetobacter baumannii, Enterobacter cloacae), including extended spectrum beta
lactamases and carbapenemases producers. All isolates showed a MoO3 NP MIC of 700
800 mg l-1. MoO3 NP produced a clear inhibition zone for S. aureus and all Gram
negative isolates at concentrations >=25 mg ml-1 and >=50 mg ml-1 for
enterococci. When the NP solutions were adjusted to pH ~7, the biocidal activity
was completely abolished. MoO3 NP create an acidic pH and show a universal
antimicrobial activity against susceptible and resistant isolates belonging to
the most relevant bacterial species responsible for hospital-acquired infections.
PMID- 29939132
TI - Dupilumab: A New Paradigm for the Treatment of Allergic Diseases.
AB - Moderate and severe forms of allergic diseases such as atopic dermatitis and
asthma are a challenge for clinicians. In these conditions, which severely affect
the quality of life of the patient and frequently have associated allergic
comorbidities, the therapeutic options are often very limited. Treatment with
systemic corticosteroids and immunosuppressants has adverse effects in the long
term, and a significant proportion of patients remain refractory to therapy. In
this context, the emerging biological drugs constitute a truly innovative
therapeutic approach. A leading example is dupilumab, a monoclonal antibody
targeting the alpha chain of the interleukin (IL)-4 receptor. Dupilumab inhibits
the biological effects of the cytokines IL-4 and IL-13, which are key drivers in
the TH2 response. The efficacy and safety profile of dupilumab in the treatment
of allergic diseases has been tested for more than 10 years in a variety of large
clinical trials in atopic dermatitis, asthma, chronic rhinosinusitis with nasal
polyposis, and eosinophilic esophagitis. In 2017, the United States Food and Drug
Administration and the European Medicines Agency approved the use of dupilumab
for the treatment of adult patients with moderateto-severe atopic dermatitis
whose disease is not adequately controlled with prescribed topical treatment. The
results of phase III clinical studies of dupilumab in patients with persistent,
uncontrolled asthma have been highly promising. The safety and tolerability
profile of dupilumab has proven to be very favorable in long-term clinical
trials. In this review, we focus on the mechanism of action of dupilumab, its
development, and its impact on daily clinical practice in allergic diseases.
PMID- 29939130
TI - A stable mode of bookmarking by TBP recruits RNA polymerase II to mitotic
chromosomes.
AB - Maintenance of transcription programs is challenged during mitosis when chromatin
becomes condensed and transcription is silenced. How do the daughter cells re
establish the original transcription program? Here, we report that the TATA
binding protein (TBP), a key component of the core transcriptional machinery,
remains bound globally to active promoters in mouse embryonic stem cells during
mitosis. Using live-cell single-molecule imaging, we observed that TBP mitotic
binding is highly stable, with an average residence time of minutes, in stark
contrast to typical TFs with residence times of seconds. To test the functional
effect of mitotic TBP binding, we used a drug-inducible degron system and found
that TBP promotes the association of RNA Polymerase II with mitotic chromosomes,
and facilitates transcriptional reactivation following mitosis. These results
suggest that the core transcriptional machinery promotes efficient transcription
maintenance globally.
PMID- 29939131
TI - Comment on 'YcgC represents a new protein deacetylase family in prokaryotes'.
AB - Lysine acetylation is a post-translational modification that is conserved from
bacteria to humans. It is catalysed by the activities of lysine
acetyltransferases, which use acetyl-CoA as the acetyl-donor molecule, and lysine
deacetylases, which remove the acetyl moiety. Recently, it was reported that YcgC
represents a new prokaryotic deacetylase family with no apparent homologies to
existing deacetylases (Tu et al., 2015). Here we report the results of
experiments which demonstrate that YcgC is not a deacetylase.
PMID- 29939133
TI - Alergologica 2015: A National Survey on Allergic Diseases in the Adult Spanish
Population.
AB - BACKGROUND AND OBJETIVE: The frequency of allergic diseases is increasing
worldwide, particularly in industrialized countries. From a clinical, management,
and public heath perspective, it is important to determine the reasons for
consulting an allergist, the distribution by frequency of allergic diseases, and
how health care is provided. Objective: Alergologica 2015 was carried out to
obtain information on clinical practice in allergy departments in Spain, and
compare it with the previous study editions. METHODS: The data cover the year
2014 and the first quarter of 2015. The target sample was 6000 patients seen at
public and private centers throughout Spain. A total of 500 allergists were
invited to participate. Data were collected on an electronic case report form.
Data were compared with the Alergologica surveys for 1992 and 2005 to identify
differences. RESULTS: The final study population comprised 2914 patients (mean
age 33.6 [18.9] years, 58% women, 17% children), of whom 6.1% were foreign-born.
The frequency distribution was as follows: rhinitis, 62%; asthma, 23.4%; drug
allergy, 17.7%; urticaria/angioedema, 11.5%; food allergy, 10.4%; contact
dermatitis, 4%; atopic dermatitis, 3%; insect venom allergy, 2%. A statistically
significant increase was observed between data from 2005 and from 2015 with
respect to the prevalence for allergic rhinitis, food allergy and drug
hypersensitivity. An increase in the prevalence of a personal history of asthma,
rhinitis, conjunctivitis, and eczema/atopic dermatitis were also observed.
Besides, the number of relevant allergens in the same patient also increased.
Most patients were referred from primary care, although a considerable percentage
were referred by ENT specialists and dermatologists. CONCLUSIONS: Increasing
trends were observed for allergic rhinitis, drug allergy, and food allergy, and a
decreasing trend was observed for asthma. Findings for other diseases remained
practically unchanged. Allergic patients are increasingly complex and present
with a myriad of atopic manifestations.
PMID- 29939134
TI - Common Proteins Located in Pigeon, Budgerigar, and Hen Droppings Related to Bird
Fancier's Lung.
PMID- 29939135
TI - Fixed Drug Eruption Due to Lorazepam.
PMID- 29939136
TI - Effects of Ole e 1 on Human Bronchial Epithelial Cells Cultured at the Air-Liquid
Interface.
PMID- 29939137
TI - Resolution of Type IV Hypersensitivity After Bone Marrow Transplantation.
PMID- 29939138
TI - Eosinophilic Esophagitis: Treatment With Different Doses of Omeprazole in
Children Under 16 Years.
PMID- 29939139
TI - Prevalence of Clonal Mast Cell Disorders in Patients Presenting With Hymenoptera
Venom Anaphylaxis Might Be Higher Than Expected.
PMID- 29939140
TI - Prevalence of Severe Atopic Dermatitis in Adults in 3 Areas of Spain.
PMID- 29939141
TI - A Case of Work-Related Donkey Milk Allergy.
PMID- 29939142
TI - Cutaneous Pseudolymphoma Secondary to Exogenous Pigment in a Polychrome Tattoo.
PMID- 29939143
TI - Delayed Hypersensitivity Reaction to Oral Dimethyl Fumarate.
PMID- 29939144
TI - Late Diagnosis of Anaphylactic Reaction to Gadolinium-Based Contrast Media by
Skin Tests 10 Years After Onset.
PMID- 29939145
TI - Hymenoptera Venom Immunotherapy: How to Safely Switch to the Same Venom From a
Different Manufacturer.
PMID- 29939146
TI - Urticaria Induced by Ingestion of Anemonia sulcata.
PMID- 29939147
TI - Blood Eosinophils, Fraction of Exhaled Nitric Oxide, and Serum Eosinophil
Cationic Protein as Surrogate Markers for Sputum Eosinophils in Asthma: Influence
of Treatment With Inhaled Corticosteroids.
PMID- 29939148
TI - Epidemiological Study of the Allergic Population in the North of Gran Canaria.
PMID- 29939149
TI - Clinical use of intracoronary imaging. Part 1: guidance and optimization of
coronary interventions. An expert consensus document of the European Association
of Percutaneous Cardiovascular Interventions.
AB - This Consensus Document is the first of two reports summarizing the views of an
expert panel organized by the European Association of Percutaneous Cardiovascular
Interventions (EAPCI) on the clinical use of intracoronary imaging including
intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first
document appraises the role of intracoronary imaging to guide percutaneous
coronary interventions (PCIs) in clinical practice. Current evidence regarding
the impact of intracoronary imaging guidance on cardiovascular outcomes is
summarized, and patients or lesions most likely to derive clinical benefit from
an imaging-guided intervention are identified. The relevance of the use of IVUS
or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and
planning the procedural strategy is discussed. Regarding post-implantation
imaging, the consensus group recommends key parameters that characterize an
optimal PCI result and provides cut-offs to guide corrective measures and
optimize the stenting result. Moreover, routine performance of intracoronary
imaging in patients with stent failure (restenosis or stent thrombosis) is
recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI
and assessing stent failures and areas that warrant further research are
critically discussed.
PMID- 29939150
TI - Magnetoresistance and valley degree of freedom in bulk bismuth.
AB - In this paper, we first review fundamental aspects of magnetoresistance in multi
valley systems based on the semiclassical theory. Then we will review
experimental evidence and theoretical understanding of magnetoresistance in an
archetypal multi-valley system, where the electric conductivity is set by the sum
of the contributions of different valleys. Bulk bismuth has three valleys with an
extremely anisotropic effective mass. As a consequence the magnetoconductivity in
each valley is extremely sensitive to the orientation of the magnetic field.
Therefore, a rotating magnetic field plays the role of a valley valve tuning the
contribution of each valley to the total conductivity. In addition to this simple
semiclassical effect, other phenomena arise in the high-field limit as a
consequence of an intricate Landau spectrum. In the vicinity of the quantum
limit, the orientation of magnetic field significantly affects the distribution
of carriers in each valley, namely, the valley polarization is induced by the
magnetic field. Moreover, experiment has found that well beyond the quantum
limit, one or two valleys become totally empty. This is the only case in
condensed matter physics where a Fermi sea is completely dried up by a magnetic
field without a metal-insulator transition. There have been two long-standing
problems on bismuth near the quantum limit: the large anisotropic Zeeman
splitting of holes, and the extra peaks in quantum oscillations, which cannot be
assigned to any known Landau levels. These problems are solved by taking into
account the interband effect due to the spin-orbit couplings for the former, and
the contributions from the twinned crystal for the latter. Up to here, the whole
spectrum can be interpreted within the one-particle theory. Finally, we will
discuss transport and thermodynamic signatures of breaking of the valley symmetry
in this system. By this term, we refer to the observed spontaneous loss of
threefold symmetry at high magnetic field and low temperature. Its theoretical
understanding is still missing. We will discuss possible explanations.
PMID- 29939151
TI - Towards developing principles of protein folding and dynamics in the cell.
AB - Proteins must fold and function in the immensely complex environment of a cell,
i.e. the cytoplasm-this is far from the ideal test-tube setting of a dilute
solution. Here we review the advances in protein folding and dynamics inside the
cell. In developing principles of protein behavior in vivo, we also begin to
understand the organization and dynamics of the cytoplasm, unifying the single
protein scale with the many-protein architectures at the subcellular scale. Our
group has significantly contributed to this frontier by characterizing the effect
of macromolecular crowding on the distribution of protein conformations.
Additionally, we provide a personal perspective on becoming a theoretical
biological physicist in the era of interdisciplinary research that has been
greatly influenced by Dr Kamal Shukla. We also share our view on the future
direction of protein folding inside a cell.
PMID- 29939152
TI - Friction-limited cell motility in confluent monolayer tissue.
AB - Mechanical forces are important factors in the development, coordination and
collective motion of cells. Based on a continuum-scale model, we consider the
influence of substrate friction on cell motility in confluent living tissue. We
test our model on the experimental data of endothelial and cancer cells. In
contrast to the commonly used drag friction, we find that solid friction best
captures the cell speed distribution. From our model, we quantify a number of
measurable physical tissue parameters, such as the ratio between the viscosity
and substrate friction.
PMID- 29939153
TI - Reflectance and fast polarization dynamics of a GaN/Si nanowire ensemble.
AB - Optical phenomena in an ensemble of high-quality GaN nanowires (NWs) grown on a
Si substrate have been studied by reflectance and time-resolved luminescence.
Such NWs form a structure that acts as a virtual layer that specifically reflects
and polarizes light and can be characterized by an effective refractive index. In
fact we have found that the NW ensembles of high NW density (high filling
fraction) behave rather like a layer of effective medium described by the Maxwell
Garnett approximation. Moreover, light extinction and strong depolarization are
observed that we assign to scattering and interference of light inside the NW
ensemble. The wavelength range of high extinction and depolarization correlates
well with transverse localization wavelength estimated for such an ensemble of
NWs, so we suppose that these effects are due to Anderson localization of light.
We also report results of time-resolved measurements of polarization of
individual emission centers including free and bound excitons (D0XA, 3.47 eV),
inversion domain boundaries (IDB, 3.45 eV) and stacking faults (SF, 3.42 eV). The
emission of the D0XA and SF lines is polarized perpendicular to GaN c-axis while
the 3.45 eV line is polarized along the c-axis which supports a hypothesis that
this line is emitted from IDBs. Time-dependent depolarization of luminescence is
observed during the first 0.1 ns after excitation and is interpreted as the
result of interaction of the emission centers with hot particles existing for a
short time after excitation.
PMID- 29939154
TI - Surface enhanced Raman scattering substrates prepared by thermal evaporation on
liquid surfaces.
AB - We present an effective surface-enhancement Raman scattering (SERS) substrate
enabled by depositing metallic film on a liquid surface at room temperature.
Thermal evaporation is used to deposit Au atoms on silicone oil surface and then
form quasi-continuous films. Due to the isotropic characteristics of the liquid
surface, this film consists of substantial nanoparticles with uniform diameter,
which is different from films fabricated on solid substrates and can be served as
an applicable substrate for SERS detection. With the assistance of this
substrate, SERS signals of rhodamine 6G were significantly enhanced, the
dependence between SERS spectra and film thickness was investigated. Analytical
simulation results confirm the experimental observations and the superiorities of
our proposed method for preparation of SERS substrate. This work provides a
potential application of metallic film deposition on free-sustained surface and
holds promise as an efficient sensor in rapid trace detection of small molecule
analytes.
PMID- 29939155
TI - Anatomy of filamentary threshold switching in amorphous niobium oxide.
AB - The threshold switching behavior of Pt/NbO x /TiN devices is investigated as a
function device area and NbO x film thickness and shown to reveal important
insight into the structure of the self-assembled switching region. The devices
exhibit combined selector-memory (1S1R) behavior after an initial voltage
controlled forming process, but exhibit symmetric threshold switching when the
RESET and SET currents are kept below a critical value. In this mode, the
threshold and hold voltages are independent of the device area and film thickness
but the threshold current (power), while independent of device area, decreases
with increasing film thickness. These results are shown to be consistent with a
structure in which the threshold switching volume is confined, both laterally and
vertically, to the region between the residual memory filament and the TiN
electrode, and where the memory filament has a core-shell structure comprising a
metallic core and a semiconducting shell. The veracity of this structure is
demonstrated by comparing experimental results with the predictions of a simple
circuit model, and more detailed finite element simulations. These results
provide further insight into the structure and operation of NbO x threshold
switching devices that have application in emerging memory and neuromorphic
computing fields.
PMID- 29939156
TI - Sensitization of TiO2 nanosheets with Cu-biphenylamine framework to enhance
photocatalytic degradation performance of toxic organic contaminants: synthesis,
mechanism and kinetic studies.
AB - TNS/Cu(X) composite materials were firstly synthesized via simple overnight
stirring of TNS in the methanolic solution of Cu complexes. The developed
TNS/Cu(X) composites had a well-designed nanostructure, in which the TNS and Cu
complexes were closely bounded with each other. The biphenylamine complexes fixed
on the TNS surface in form of nanocapsules, which were confirmed by TEM and SEM,
thus improving the surface area and subsequently charge separation. Innovatively
merged photocatalysts of Cu complexes with TNS were successfully verified for
photocatalytic mineralization of colored and colorless organic contaminants under
the visible light degradation. As compared to original TNS, TNS/Cu(BA) showed
prominent improvement in the catalytic actions. Kinetics i.e. t 1/2 (half-life
times period), K app, and R 2 (linear regression co-efficient) were also studied.
The amended materials created charge separation, by means of electrons gathering
at the higher CB, and holes gathering at the lower level valence band of the Cu
complex, therefore improving mineralization efficiency of the electrons and
holes. TNS/Cu(BA) degrade 99%-99.6% of methyl orange (MO) and rhodamine B (RhB)
dyes at 120 min, and 160 min, respectively, and 68% of phenol and 53% of TCP were
destroyed in 180 min. The resilient holes can directly destroy MO, RhB, phenol,
and TCP.
PMID- 29939157
TI - Blister-based-laser-induced-forward-transfer: a non-contact, dry laser-based
transfer method for nanomaterials.
AB - We show that blister-based-laser-induced forward-transfer can be used to cleanly
desorb and transfer nano- and micro-scale particles between substrates without
exposing the particles to the laser radiation or to any chemical treatment that
could damage the intrinsic electronic and optical properties of the materials.
The technique uses laser pulses to induce the rapid formation of a blister on a
thin metal layer deposited on glass via ablation at the metal/glass interface.
Femtosecond laser pulses are advantageous for forming beams of molecules or small
nanoparticles with well-defined velocity and narrow angular distributions. Both
fs and ns laser pulses can be used to cleanly transfer larger nanoparticles
including relatively fragile monolayer 2D transition metal dichalcogenide
crystals and for direct transfer of nanoparticles from chemical vapour deposition
growth substrates, although the mechanisms for inducing blister formation are
different.
PMID- 29939158
TI - Atomic-scale study of stacking faults in Zr hydrides and implications on hydride
formation.
AB - We performed atomic-scale ab initio calculations to investigate the stacking
fault (SF) properties of the metastable zeta-Zr2H zirconium hydride. The effect
of H near the SF was found to entail the existence of negative SF energies,
showing that the zeta compound is probably unstable with respect to shearing in
the basal plane. The effect of temperature on SFs was investigated by means of
free energy calculations in the quasiharmonic approximation. This evidenced
unexpectedly large temperature effects, confirming the main conclusions drawn at
0 K, in particular the zeta mechanical instability. The complex behaviour of H
atoms during the shear process suggested zeta-hcp -> Zr2H[Formula: see text]
fcc as a plausible shear path leading to an fcc compound with same composition as
zeta. Finally, as shown by an analysis based on microelasticity, this
Zr2H[Formula: see text]-fcc intermediate compound may be relevant for better
interpreting the currently intricate issue of hydride habit planes in zirconium.
PMID- 29939159
TI - Enhancement of stem cell engraftment on a WHIM.
AB - WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a
genetic autoimmune disorder that results from gain-of-function mutations in the
gene encoding chemokine receptor CXCR4. A previous study characterized a patient
with WHIM who underwent a chromothriptic event that resulted in spontaneous
deletion of the WHIM allele in a single hematopoietic stem cell and subsequent
cure of the disease. In this issue of the JCI, Gao et al. extend this work and
show that Cxcl4-haplosufficient bone marrow has a selective advantage for long
term engraftment in murine WHIM models. Moreover, successful engraftment occurred
without prior conditioning of recipients. Together, these results have important
implications for improving hematopoietic stem/progenitor cell transplant not only
for patients with WHIM but also for all patients who may require the procedure.
PMID- 29939160
TI - Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk
neuroblastoma.
AB - High-risk neuroblastoma is a devastating malignancy with very limited therapeutic
options. Here, we identify withaferin A (WA) as a natural ferroptosis-inducing
agent in neuroblastoma, which acts through a novel double-edged mechanism. WA
dose-dependently either activates the nuclear factor-like 2 pathway through
targeting of Kelch-like ECH-associated protein 1 (noncanonical ferroptosis
induction) or inactivates glutathione peroxidase 4 (canonical ferroptosis
induction). Noncanonical ferroptosis induction is characterized by an increase in
intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which
is sufficient to induce ferroptosis. This double-edged mechanism might explain
the superior efficacy of WA as compared with etoposide or cisplatin in killing a
heterogeneous panel of high-risk neuroblastoma cells, and in suppressing the
growth and relapse rate of neuroblastoma xenografts. Nano-targeting of WA allows
systemic application and suppressed tumor growth due to an enhanced accumulation
at the tumor site. Collectively, our data propose a novel therapeutic strategy to
efficiently kill cancer cells by ferroptosis.
PMID- 29939161
TI - HSD3B1(1245A>C) variant regulates dueling abiraterone metabolite effects in
prostate cancer.
AB - BACKGROUND: A common germline variant in HSD3B1(1245A>C) encodes for a
hyperactive 3beta-hydroxysteroid dehydrogenase 1 (3betaHSD1) missense that
increases metabolic flux from extragonadal precursor steroids to DHT synthesis in
prostate cancer. Enabling of extragonadal DHT synthesis by HSD3B1(1245C) predicts
for more rapid clinical resistance to castration and sensitivity to extragonadal
androgen synthesis inhibition. HSD3B1(1245C) thus appears to define a subgroup of
patients who benefit from blocking extragonadal androgens. However, abiraterone,
which is administered to block extragonadal androgens, is a steroidal drug that
is metabolized by 3betaHSD1 to multiple steroidal metabolites, including 3-keto
5alpha-abiraterone, which stimulates the androgen receptor. Our objective was to
determine if HSD3B1(1245C) inheritance is associated with increased 3-keto-5alpha
abiraterone synthesis in patients. METHODS: First, we characterized the
pharmacokinetics of 7 steroidal abiraterone metabolites in 15 healthy volunteers.
Second, we determined the association between serum 3-keto-5alpha-abiraterone
levels and HSD3B1 genotype in 30 patients treated with abiraterone acetate (AA)
after correcting for the determined pharmacokinetics. RESULTS: Patients who
inherit 0, 1, and 2 copies of HSD3B1(1245C) have a stepwise increase in
normalized 3-keto-5alpha-abiraterone (0.04 ng/ml, 2.60 ng/ml, and 2.70 ng/ml,
respectively; P = 0.002). CONCLUSION: Increased generation of 3-keto-5alpha
abiraterone in patients with HSD3B1(1245C) might partially negate abiraterone
benefits in these patients who are otherwise more likely to benefit from CYP17A1
inhibition. FUNDING: Prostate Cancer Foundation Challenge Award, National Cancer
Institute.
PMID- 29939162
TI - The COPII cargo adapter SEC24C is essential for neuronal homeostasis.
AB - SEC24 family members are components of the coat protein complex II (COPII)
machinery that interact directly with cargo or with other adapters to ensure
proper sorting of secretory cargo into COPII vesicles. SEC24C is 1 of 4 mammalian
SEC24 paralogs (SEC24A-D), which segregate into 2 subfamilies on the basis of
sequence homology (SEC24A/SEC24B and SEC24C/SEC24D). Here, we demonstrate that
postmitotic neurons, unlike professional secretory cells in other tissues, are
exquisitely sensitive to loss of SEC24C. Conditional KO of Sec24c in neural
progenitors during embryogenesis caused perinatal mortality and microcephaly,
with activation of the unfolded protein response and apoptotic cell death of
postmitotic neurons in the murine cerebral cortex. The cell-autonomous function
of SEC24C in postmitotic neurons was further highlighted by the loss of cell
viability caused by disrupting Sec24c expression in forebrain neurons of mice
postnatally and in differentiated neurons derived from human induced pluripotent
stem cells. The neuronal cell death associated with Sec24c deficiency was rescued
in knockin mice expressing Sec24d in place of Sec24c. These data suggest that
SEC24C is a major cargo adapter for COPII-dependent transport in postmitotic
neurons in developing and adult brains and that its functions overlap at least
partially with those of SEC24D in mammals.
PMID- 29939163
TI - Fibrin films: overlooked hemostatic barriers against microbial infiltration.
AB - The hemostatic response to vascular injury culminates in a fibrin clot network
that forms an initial barrier to blood loss and also contributes to microbial
host defense. Fibrinogen is cleaved by thrombin into fibrin monomers that
spontaneously polymerize into protofibrils and form the extensive fiber networks
characteristic of blood clots. In this issue of the JCI, Macrae and colleagues
characterize an alternative fibrin structure in which fibrinogen and fibrin
assemble into a continuous 2D film at the exterior face of the fibrin clot
network. Fibrin films connect to the underlying fiber network through tethering
fibers and provide a protective barrier to microbial infiltration. These findings
shed new light on a previously overlooked mechanism of fibrin assembly at the
clot surface and provide a link between hemostasis and innate immunity.
PMID- 29939164
TI - Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis.
AB - Genetic testing is the most reliable test for hereditary transthyretin related
amyloidosis and should be performed in most cases of transthyretin amyloidosis
(ATTR). ATTR is a rare but fatal disease with heterogeneous phenotypes;
therefore, the diagnosis is sometimes delayed. With increasing attention and
broader recognition on early manifestations of ATTR as well as emerging
treatments, appropriate diagnostic studies, including the transthyretin (TTR)
genetic test, to confirm the types and variants of ATTR are therefore fundamental
to improve the prognosis. Genetic analyses with polymerase chain reaction (PCR)
methods confirm the presence of TTR point mutations much more quickly and safer
than conventional methods such as southern blot. Herein, we demonstrate genetic
confirmation of the ATTR Ala97Ser mutation, the most common endemic mutation in
Taiwan. The protocol comprises four main steps: collecting whole blood specimen,
DNA extraction, genetic analysis of all four TTR exons with PCR, and DNA
sequencing.
PMID- 29939165
TI - Generation and Coherent Control of Pulsed Quantum Frequency Combs.
AB - We present a method for the generation and coherent manipulation of pulsed
quantum frequency combs. Until now, methods of preparing high-dimensional states
on-chip in a practical way have remained elusive due to the increasing complexity
of the quantum circuitry needed to prepare and process such states. Here, we
outline how high-dimensional, frequency-bin entangled, two-photon states can be
generated at a stable, high generation rate by using a nested-cavity, actively
mode-locked excitation of a nonlinear micro-cavity. This technique is used to
produce pulsed quantum frequency combs. Moreover, we present how the quantum
states can be coherently manipulated using standard telecommunications components
such as programmable filters and electro-optic modulators. In particular, we show
in detail how to accomplish state characterization measurements such as density
matrix reconstruction, coincidence detection, and single photon spectrum
determination. The presented methods form an accessible, reconfigurable, and
scalable foundation for complex high-dimensional state preparation and
manipulation protocols in the frequency domain.
PMID- 29939166
TI - Characterization of Aquatic Biofilms with Flow Cytometry.
AB - Biofilms are dynamic consortia of microorganism that play a key role in
freshwater ecosystems. By changing their community structure, biofilms respond
quickly to environmental changes and can be thus used as indicators of water
quality. Currently, biofilm assessment is mostly based on integrative and
functional endpoints, such as photosynthetic or respiratory activity, which do
not provide information on the biofilm community structure. Flow cytometry and
computational visualization offer an alternative, sensitive, and easy-to-use
method for assessment of the community composition, particularly of the
photoautotrophic part of freshwater biofilms. It requires only basic sample
preparation, after which the entire sample is run through the flow cytometer. The
single-cell optical and fluorescent information is used for computational
visualization and biological interpretation. Its main advantages over other
methods are the speed of analysis and the high-information-content nature. Flow
cytometry provides information on several cellular and biofilm traits in a single
measurement: particle size, density, pigment content, abiotic content in the
biofilm, and coarse taxonomic information. However, it does not provide
information on biofilm composition on the species level. We see high potential in
the use of the method for environmental monitoring of aquatic ecosystems and as
an initial biofilm evaluation step that informs downstream detailed
investigations by complementary and more detailed methods.
PMID- 29939167
TI - Preparation of Drosophila Larval Samples for Gas Chromatography-Mass Spectrometry
(GC-MS)-based Metabolomics.
AB - Recent advances in the field of metabolomics have established the fruit fly
Drosophila melanogaster as a powerful genetic model for studying animal
metabolism. By combining the vast array of Drosophila genetic tools with the
ability to survey large swaths of intermediary metabolism, a metabolomics
approach can reveal complex interactions between diet, genotype, life-history
events, and environmental cues. In addition, metabolomics studies can discover
novel enzymatic mechanisms and uncover previously unknown connections between
seemingly disparate metabolic pathways. In order to facilitate more widespread
use of this technology among the Drosophila community, here we provide a detailed
protocol that describes how to prepare Drosophila larval samples for gas
chromatography-mass spectrometry (GC-MS)-based metabolomic analysis. Our protocol
includes descriptions of larval sample collection, metabolite extraction,
chemical derivatization, and GC-MS analysis. Successful completion of this
protocol will allow users to measure the relative abundance of small polar
metabolites, including amino acids, sugars, and organic acids involved in
glycolysis and the TCA cycles.
PMID- 29939168
TI - Intracavernosal Pressure Recording to Evaluate Erectile Function in Rodents.
AB - Erectile dysfunction (ED) is defined as the inability to attain or keep an
erection of the penis, and this has become a prevalent male sexual disorder.
Rodents are employed by many studies to research the physiology/pathology of
erectile function. Erectile function in rodents can be evaluated by measuring the
intracavernosal pressure (ICP). In practice, ICP can be monitored following
electrical stimulation of the cavernous nerves (CNs). The arterial pressure of
the carotid artery (the mean arterial pressure) is used as the reference for ICP.
Using ICP recording protocols, many key parameters of erectile function can be
measured from the ICP response curve. The ICP measurement provides more
information than the apomorphine-induced penile erection test, and is cheaper
than telemetric monitoring of the corpus spongiosum penis, making this method the
most popular one to evaluate erectile function. However, compared to the easily
performed APO-induced erectile function test, successful ICP recordings require
attention to detail, practice, and adherence to the operation method. In this
work, an introduction to ICP recording in rats is provided to complement the
procedure efficiently.
PMID- 29939169
TI - Obtaining 3D Chemical Maps by Energy Filtered Transmission Electron Microscopy
Tomography.
AB - Energy filtered transmission electron microscopy tomography (EFTEM tomography)
can provide three-dimensional (3D) chemical maps of materials at a nanometric
scale. EFTEM tomography can separate chemical elements that are very difficult to
distinguish using other imaging techniques. The experimental protocol described
here shows how to create 3D chemical maps to understand the chemical distribution
and morphology of a material. Sample preparation steps for data segmentation are
presented. This protocol permits the 3D distribution analysis of chemical
elements in a nanometric sample. However, it should be noted that currently, the
3D chemical maps can only be generated for samples that are not beam sensitive,
since the recording of filtered images requires long exposure times to an intense
electron beam. The protocol was applied to quantify the chemical distribution of
the components of two different heterogeneous catalyst supports. In the first
study, the chemical distribution of aluminum and titanium in titania-alumina
supports was analyzed. The samples were prepared using the swing-pH method. In
the second, the chemical distribution of aluminum and silicon in silica-alumina
supports that were prepared using the sol-powder and mechanical mixture methods
was examined.
PMID- 29939171
TI - The TreadWheel: Interval Training Protocol for Gently Induced Exercise in
Drosophila melanogaster.
AB - The incidence of complex metabolic diseases has increased as a result of a
widespread transition towards lifestyles of increased caloric intake and lowered
activity levels. These multifactorial diseases arise from a combination of
genetic, environmental, and behavioral factors. One such complex disease is
Metabolic Syndrome (MetS), which is a cluster of metabolic disorders, including
hypertension, hyperglycemia, and abdominal obesity. Exercise and dietary
intervention are the primary treatments recommended by doctors to mitigate
obesity and its subsequent metabolic diseases. Exercise intervention, in
particular aerobic interval training, stimulates favorable changes in the common
risk factors for Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD),
and other conditions. With the influx of evidence describing the therapeutic
effect exercise has on metabolic health, establishing a system that models
exercise in a controlled setting provides a valuable tool for assessing the
effects of exercise in an experimental context. Drosophila melanogaster is a
great tool for investigating the physiological and molecular changes that result
from exercise intervention. The flies have short lifespans and similar mechanisms
of metabolizing nutrients when compared to humans. To induce exercise in
Drosophila, we developed a machine called the TreadWheel, which utilizes the
fly's innate, negative geotaxis tendency to gently induce climbing. This enables
researchers to perform experiments on large cohorts of genetically diverse flies
to better understand the genotype-by-environment interactions underlying the
effects of exercise on metabolic health.
PMID- 29939170
TI - Probing the Roles of Physical Forces in Early Chick Embryonic Morphogenesis.
AB - Embryonic development is traditionally studied from the perspective of
biomolecular genetics, but the fundamental importance of mechanics in
morphogenesis is becoming increasingly recognized. In particular, the embryonic
chick heart and brain tube, which undergo drastic morphological changes as they
develop, are among the prime candidates to study the role of physical forces in
morphogenesis. Progressive ventral bending and rightward torsion of the tubular
embryonic chick brain happen at the earliest stage of organ-level left-right
asymmetry in chick embryonic development. The vitelline membrane (VM) constrains
the dorsal side of the embryo and has been implicated in providing the force
necessary to induce torsion of the developing brain. Here we present a
combination of new ex-ovo experiments and physical modeling to identify the
mechanics of brain torsion. At Hamburger-Hamilton stage 11, embryos are harvested
and cultured ex ovo (in media). The VM is subsequently removed using a pulled
capillary tube. By controlling the level of the fluid and subjecting the embryo
to a fluid-air interface, the fluid surface tension of the media can be used to
replace the mechanical role of the VM. Microsurgery experiments were also
performed to alter the position of the heart to find the resultant change in the
chirality of brain torsion. Results from this protocol illustrate the fundamental
roles of mechanics in driving morphogenesis.
PMID- 29939172
TI - Collecting Hair Samples for Hair Cortisol Analysis in African Americans.
AB - The hormone cortisol is typically assessed in saliva, serum, or urine samples.
More recently, cortisol has been successfully extracted from hair, including
humans. The advantage of hair cortisol concentration is that it reflects a
retrospective representation of hypothalamic-pituitary-adrenal (HPA) axis
function over time, much like hemoglobin A1C represents glycemic control.
However, obtaining hair samples can be challenging, due to the cultural beliefs
and hair care practices of minority participants. For example, African Americans
may be reluctant to provide samples. Additionally, few researchers are trained to
collect hair samples from African Americans. The purpose of this paper is to
present a culturally informed protocol to help researchers obtain hair samples
from African Americans. To illustrate the representative results of this protocol
implementation, de-identified data from African Americans that participated in a
community-based study on chronic stress are provided. Hair practice preferences
are assessed. The participants are made comfortable by showing pictures of hair
samples prior to cutting their hair. The single strain twist and gently pull
method is used to collect approximately 30 - 50 strands of hair from the
posterior vertex region of the scalp. This protocol will significantly improve
collection of hair samples from African Americans.
PMID- 29939173
TI - CRISPR-mediated Loss of Function Analysis in Cerebellar Granule Cells Using In
Utero Electroporation-based Gene Transfer.
AB - Brain malformation is often caused by genetic mutations. Deciphering the
mutations in patient-derived tissues has identified potential causative factors
of the diseases. To validate the contribution of a dysfunction of the mutated
genes to disease development, the generation of animal models carrying the
mutations is one obvious approach. While germline genetically engineered mouse
models (GEMMs) are popular biological tools and exhibit reproducible results, it
is restricted by time and costs. Meanwhile, non-germline GEMMs often enable
exploring gene function in a more feasible manner. Since some brain diseases
(e.g., brain tumors) appear to result from somatic but not germline mutations,
non-germline chimeric mouse models, in which normal and abnormal cells coexist,
could be helpful for disease-relevant analysis. In this study, we report a method
for the induction of CRISPR-mediated somatic mutations in the cerebellum.
Specifically, we utilized conditional knock-in mice, in which Cas9 and GFP are
chronically activated by the CAG (CMV enhancer/chicken beta-actin) promoter after
Cre-mediated recombination of the genome. The self-designed single-guide RNAs
(sgRNAs) and the Cre recombinase sequence, both encoded in a single plasmid
construct, were delivered into cerebellar stem/progenitor cells at an embryonic
stage using in utero electroporation. Consequently, transfected cells and their
daughter cells were labeled with green fluorescent protein (GFP), thus
facilitating further phenotypic analyses. Hence, this method is not only showing
electroporation-based gene delivery into embryonic cerebellar cells but also
proposing a novel quantitative approach to assess CRISPR-mediated loss-of
function phenotypes.
PMID- 29939174
TI - Determination of the Settling Rate of Clay/Cyanobacterial Floccules.
AB - The mechanisms underpinning the deposition of fine-grained, organic-rich
sediments are still largely debated. Specifically, the impact of the interaction
of clay particles with reactive, planktonic cyanobacterial cells to the
sedimentary record is under studied. This interaction is a potentially major
contributor to shale depositional models. Within a lab setting, the flocculation
and sedimentation rates of these materials can be examined and measured in a
controlled environment. Here, we detail a protocol for measuring the
sedimentation rate of cyanobacterial/clay mixtures. This methodology is
demonstrated through the description of two sample experiments: the first uses
kaolin (a dehydrated form of kaolinite) and Synechococcus sp. PCC 7002 (a marine
coccoid cyanobacteria), and the second uses kaolin and Synechocystis sp. PCC 6803
(a freshwater coccoid cyanobacteria). Cyanobacterial cultures are mixed with
varying amounts of clay within a specially designed tank apparatus optimized to
allow continuous, real-time video and photographic recording. The sampling
procedures are detailed as well as a post-collection protocol for precise
measurement of chlorophyll a from which the concentration of cyanobacterial cells
remaining in suspension can be determined. Through experimental replication, a
profile is constructed that displays sedimentation rate.
PMID- 29939175
TI - Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference
Paradigm.
AB - The present protocol describes the Conditioned Place Preference (CPP) as a model
of relapse in drug addiction. In this model, animals are first trained to acquire
a conditioned place preference in a drug-paired compartment, and after the post
conditioning test, they perform several sessions to extinguish the established
preference. The CPP permits the evaluation of the conditioned rewarding effects
of drugs related to environmental cues. Then, the extinguished CPP can be
robustly reinstated by the non-contingent administration of a priming dose of the
drug, and by exposure to stressful stimuli. Both methods will be explained here.
When the animal reinitiates the behavioral response, a reinstatement of the
conditioned reward is considered to have taken place. The main advantages of this
protocol are that it is non-invasive, inexpensive, and simple with good validity
criteria. In addition, it allows the study of different environmental
manipulations, such as stress or diet, which can modulate relapse into drug
seeking behaviors. However, one limitation is that if the researcher aims to
explore the motivation and primary reinforcing effects of the drug, it should be
complemented with self-administration procedures, as they involve operant
responses of animals.
PMID- 29939176
TI - A Yeast 2-Hybrid Screen in Batch to Compare Protein Interactions.
AB - Screening for protein-protein interactions using the yeast 2-hybrid assay has
long been an effective tool, but its use has largely been limited to the
discovery of high-affinity interactors that are highly enriched in the library of
interacting candidates. In a traditional format, the yeast 2-hybrid assay can
yield too many colonies to analyze when conducted at low stringency where low
affinity interactors might be found. Moreover, without a comprehensive and
complete interrogation of the same library against different bait plasmids, a
comparative analysis cannot be achieved. Although some of these problems can be
addressed using arrayed prey libraries, the cost and infrastructure required to
operate such screens can be prohibitive. As an alternative, we have adapted the
yeast 2-hybrid assay to simultaneously uncover dozens of transient and static
protein interactions within a single screen utilizing a strategy termed DEEPN
(Dynamic Enrichment for Evaluation of Protein Networks), which incorporates high
throughput DNA sequencing and computation to follow the evolution of a population
of plasmids that encode interacting partners. Here, we describe customized
reagents and protocols that allow a DEEPN screen to be executed easily and cost
effectively.
PMID- 29939177
TI - CMAP Scan MUNE (MScan) - A Novel Motor Unit Number Estimation (MUNE) Method.
AB - Like other methods for motor unit number estimation (MUNE), compound muscle
action potential (CMAP) scan MUNE (MScan) is a non-invasive electrophysiologic
method to estimate the number of functioning motor units in a muscle. MUNE is an
important tool for the assessment of neuropathies and neuronopathies. Unlike most
MUNE methods in use, MScan assesses all the motor units in a muscle, by fitting a
model to a detailed stimulus-response curve, or CMAP scan. It thereby avoids the
bias inherent in all MUNE methods based on extrapolating from a small sample of
units. Like 'Bayesian MUNE,' MScan analysis works by fitting a model, made up of
motor units with different amplitudes, thresholds, and threshold variabilities,
but the fitting method is quite different, and completed within five minutes,
rather than several hours. The MScan off-line analysis works in two stages:
first, a preliminary model is generated based on the slope and variance of the
points in the scan, and second, this model is then refined by adjusting all the
parameters to improve the fit between the original scan and scans generated by
the model. This new method has been tested for reproducibility and recording time
on 22 amyotrophic lateral sclerosis (ALS) patients and 20 healthy controls, with
each test repeated twice by two blinded physicians. MScan showed excellent intra-
and inter-rater reproducibility with ICC values of >0.98 and a coefficient of
variation averaging 12.3 +/- 1.6%. There was no difference in the intra-rater
reproducibility between the two observers. Average recording time was 6.27 +/-
0.27 min. This protocol describes how to record a CMAP scan and how to use the
MScan software to derive an estimate of the number and sizes of the functioning
motor units. MScan is a fast, convenient, and reproducible method, which may be
helpful in diagnoses and monitoring disease progression in neuromuscular
disorders.
PMID- 29939178
TI - A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible
Electroporation.
AB - Pancreatic cancer (PC), a disease which kills approximately 40,000 patients each
year in the US, has successfully evaded several therapeutic approaches including
the promising immunotherapeutic strategies. Irreversible electroporation (IRE) is
a non-thermal ablation technique that induces tumor cell death without
destruction of adjacent collagenous structures, thus enabling the procedure to be
performed in tumors very close to blood vessels. Unlike thermal ablation
techniques, IRE results in gradual apoptotic cell death, along with immediate
ablation induced necrosis, and is currently in clinical use for selected patients
with locally advanced PC. An ablative, non-target specific procedure like IRE can
induce a myriad of responses in the tumor microenvironment. A few studies have
addressed the effects of IRE on tumor growth in other tumor types, but none have
focused on PC. We have developed a syngeneic mouse model of PC in which
subcutaneous (SQ) and orthotopic tumors can be successfully treated with IRE in a
highly controlled setting, facilitating various longitudinal studies post
procedure. This animal model serves as a robust system to study the effects of
IRE and ways to improve the clinical efficacy of IRE.
PMID- 29939179
TI - Dried Blood and Serum Spots As A Useful Tool for Sample Storage to Evaluate
Cancer Biomarkers.
AB - Blood sample quality is crucial to ensure accurate downstream analyses such as
real-time PCR or ELISA. Correct storage of biological materials is the starting
point to achieve reproducible and reliable results. All samples should be treated
in the same way from blood collection to storage. Depending on the analyses to be
performed, whole blood and serum samples should be stored at -20 degrees C or
80 degrees C until use. Blood/serum samples should also be aliquoted to avoid
multiple freeze-thawing. Another important issue is the sample conditions during
shipment from one laboratory to another. If dry ice is not available or the
shipment takes longer than a few days, alternative approaches are needed. One
option is to use filter paper for blood collection. Here, we propose a method for
blood and serum sample collection that takes advantage of dried blood spots (DBS)
and dried serum spots (DSS). We developed the procedure to extract DNA from DBS
for the downstream evaluation of some single nucleotide polymorphisms (SNPs) by
real time PCR. We also optimized an ELISA assay starting from proteins eluted
from DSS. This method can be used with other ELISA assays or procedures
evaluating proteins.
PMID- 29939180
TI - Enrichment and Characterization of the Tumor Immune and Non-immune
Microenvironments in Established Subcutaneous Murine Tumors.
AB - The tumor immune microenvironment (TIME) has recently been recognized as a
critical mediator of treatment response in solid tumors, especially for
immunotherapies. Recent clinical advances in immunotherapy highlight the need for
reproducible methods to accurately and thoroughly characterize the tumor and its
associated immune infiltrate. Tumor enzymatic digestion and flow cytometric
analysis allow broad characterization of numerous immune cell subsets and
phenotypes; however, depth of analysis is often limited by fluorophore
restrictions on panel design and the need to acquire large tumor samples to
observe rare immune populations of interest. Thus, we have developed an effective
and high throughput method for separating and enriching the tumor immune
infiltrate from the non-immune tumor components. The described tumor digestion
and centrifugal density-based separation technique allows separate
characterization of tumor and tumor immune infiltrate fractions and preserves
cellular viability, and thus, provides a broad characterization of the tumor
immunologic state. This method was used to characterize the extensive spatial
immune heterogeneity in solid tumors, which further demonstrates the need for
consistent whole tumor immunologic profiling techniques. Overall, this method
provides an effective and adaptable technique for the immunologic
characterization of subcutaneous solid murine tumors; as such, this tool can be
used to better characterize the tumoral immunologic features and in the
preclinical evaluation of novel immunotherapeutic strategies.
PMID- 29939181
TI - A Protocol to Acquire the Degenerative Tenocyte from Humans.
AB - Tendinopathy, a painful condition that develops in response to tendon
degeneration, is on the rise in the developed world due to increasing physical
activity and longer life expectancy. Despite its increasing prevalence, the
underlying pathogenesis still remains unclear, and treatment is generally
symptomatic. Recently, numerous therapeutic options, including growth factors,
stem cells, and gene therapy, were investigated in hopes of enhancing the healing
potency of the degenerative tendon. However, the majority of these research
studies were conducted only on animal models or healthy human tenocytes. Despite
some studies using pathological tenocytes, to the best of our knowledge there is
currently no protocol describing how to obtain human degenerative tenocytes. The
aim of this study is to describe a standard protocol for acquiring human
degenerative tenocytes. Initially, the tendon tissue was harvested from a patient
with lateral epicondylitis during surgery. Then biopsy samples were taken from
the extensor carpi radialis brevis tendon corresponding to structural changes
observed at the time of surgery. All of the harvested tendons appeared to be
dull, gray, friable, and edematous, which made them visually distinct from the
healthy ones. Tenocytes were cultured and used for experiments. Meanwhile, half
of the harvested tissues were analyzed histologically, and it was shown that they
shared the same key features of tendinopathy (angiofibroblastic dysplasia or
hyperplasia). A secondary analysis by immunocytochemistry confirmed that the
cultured cells were tenocytes with the majority of the cells having positive
stains for mohawk and tenomodulin proteins. The qualities of the degenerative
nature of tenocytes were then determined by comparing the cells with the healthy
control using a proliferation assay or qRT-PCR. The degenerative tenocyte
displayed a higher proliferation rate and similar gene expression patterns of
tendinopathy that matched previous reports. Overall, this new protocol might
provide a useful tool for future studies of tendinopathy.
PMID- 29939182
TI - Homochronic Transplantation of Interneuron Precursors into Early Postnatal Mouse
Brains.
AB - Neuronal fate determination and maturation requires an intricate interplay
between genetic programs and environmental signals. However, disentangling the
roles of intrinsic vs. extrinsic mechanisms that regulate this differentiation
process is a conundrum for all developmental neurobiologists. This issue is
magnified for GABAergic interneurons, an incredibly heterogeneous cell population
that is born from transient embryonic structures and undergo a protracted
migratory phase to disperse throughout the telencephalon. To explore how
different brain environments affect interneuron fate and maturation, we developed
a protocol for harvesting fluorescently labeled immature interneuron precursors
from specific brain regions in newborn mice (P0-P2). At this age, interneuron
migration is nearly complete and these cells are residing in their final resting
environments with relatively little synaptic integration. Following collection of
single cell solutions via flow cytometry, these interneuron precursors are
transplanted into P0-P2 wildtype postnatal pups. By performing both homotopic
(e.g., cortex-to-cortex) or heterotopic (e.g., cortex-to-hippocampus)
transplantations, one can assess how challenging immature interneurons in new
brain environments affects their fate, maturation, and circuit integration.
Brains can be harvested in adult mice and assayed with a wide variety of posthoc
analysis on grafted cells, including immunohistochemical, electrophysiological
and transcriptional profiling. This general approach provides investigators with
a strategy to assay how distinct brain environments can influence numerous
aspects of neuron development and identify if specific neuronal characteristics
are primarily driven by hardwired genetic programs or environmental cues.
PMID- 29939183
TI - Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naive-like
State with Improved Multilineage Differentiation Potency.
AB - Naive human pluripotent stem cells (N-hPSC) with improved functionality may have
a wide impact in regenerative medicine. The goal of this protocol is to
efficiently revert lineage-primed, conventional human pluripotent stem cells
(hPSC) maintained on either feeder-free or feeder-dependent conditions to a naive
like pluripotency with improved functionality. This chemical naive reversion
method employs the classical leukemia inhibitory factor (LIF), GSK3beta, and
MEK/ERK inhibition cocktail (LIF-2i), supplemented with only a tankyrase
inhibitor XAV939 (LIF-3i). LIF-3i reverts conventional hPSC to a stable
pluripotent state adopting biochemical, transcriptional, and epigenetic features
of the human pre-implantation epiblast. This LIF-3i method requires minimal cell
culture manipulation and is highly reproducible in a broad repertoire of human
embryonic stem cell (hESC) and transgene-free human induced pluripotent stem cell
(hiPSC) lines. The LIF-3i method does not require a re-priming step prior to the
differentiation; N-hPSC can be differentiated directly with extremely high
efficiencies and maintain karyotypic and epigenomic stabilities (including at
imprinted loci). To increase the universality of the method, conventional hPSC
are first cultured in the LIF-3i cocktail supplemented with two additional small
molecules that potentiate protein kinase A (forskolin) and sonic hedgehog (sHH)
(purmorphamine) signaling (LIF-5i). This brief LIF-5i adaptation step
significantly enhances the initial clonal expansion of conventional hPSC and
permits them to be subsequently naive-reverted with LIF-3i alone in bulk
quantities, thus obviating the need for picking/subcloning rare N-hPSC colonies
later. LIF-5i-stabilized hPSCs are subsequently maintained in LIF-3i alone
without the need of anti-apoptotic molecules. Most importantly, LIF-3i reversion
markedly improves the functional pluripotency of a broad repertoire of
conventional hPSC by decreasing their lineage-primed gene expression and erasing
the interline variability of directed differentiation commonly observed amongst
independent hPSC lines. Representative characterizations of LIF-3i-reverted N
hPSC are provided, and experimental strategies for functional comparisons of
isogenic hPSC in lineage-primed vs. naive-like states are outlined.
PMID- 29939184
TI - Methods of Ex Situ and In Situ Investigations of Structural Transformations: The
Case of Crystallization of Metallic Glasses.
AB - We demonstrate the use of two nuclear-based analytical methods that can follow
the modifications of microstructural arrangement of iron-based metallic glasses
(MGs). Despite their amorphous nature, the identification of hyperfine
interactions unveils faint structural modifications. For this purpose, we have
employed two techniques that utilize nuclear resonance among nuclear levels of a
stable 57Fe isotope, namely Mossbauer spectrometry and nuclear forward scattering
(NFS) of synchrotron radiation. The effects of heat treatment upon
(Fe2.85Co1)77Mo8Cu1B14 MG are discussed using the results of ex situ and in situ
experiments, respectively. As both methods are sensitive to hyperfine
interactions, information on structural arrangement as well as on magnetic
microstructure is readily available. Mossbauer spectrometry performed ex situ
describes how the structural arrangement and magnetic microstructure appears at
room temperature after the annealing under certain conditions (temperature,
time), and thus this technique inspects steady states. On the other hand, NFS
data are recorded in situ during dynamically changing temperature and NFS
examines transient states. The use of both techniques provides complementary
information. In general, they can be applied to any suitable system in which it
is important to know its steady state but also transient states.
PMID- 29939185
TI - Characterization of Synthetic Polymers via Matrix Assisted Laser Desorption
Ionization Time of Flight (MALDI-TOF) Mass Spectrometry.
AB - There are many techniques that can be employed in the characterization of
synthetic homopolymers, but few provide as useful of information for end group
analysis as matrix-assisted laser desorption ionization time of flight mass
spectrometry (MALDI-TOF MS). This tutorial demonstrates methods for optimization
of the sample preparation, spectral acquisition, and data analysis of synthetic
polymers using MALDI-TOF MS. Critical parameters during sample preparation
include the selection of the matrix, identification of an appropriate
cationization salt, and tuning the relative proportions of the matrix, cation,
and analyte. The acquisition parameters, such as mode (linear or reflector),
polarization (positive or negative), acceleration voltage, and delay time, are
also important. Given some knowledge of the chemistry involved to synthesize the
polymer and optimizing both the data acquisition parameters and the sample
preparation conditions, spectra should be obtained with sufficient resolution and
mass accuracy to enable the unambiguous determination of the end groups of most
homopolymers (masses below 10,000) in addition to the repeat unit mass and the
overall molecular weight distribution. Though demonstrated on a limited set of
polymers, these general techniques are applicable to a much wider range of
synthetic polymers for determining mass distributions, though end group
determination is only possible for homopolymers with narrow dispersity.
PMID- 29939186
TI - Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational
Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry.
AB - Living organisms regularly need to cope with fluctuating environments during
their life cycle, including changes in temperature, pH, the accumulation of
reactive oxygen species, and more. These fluctuations can lead to a widespread
protein unfolding, aggregation, and cell death. Therefore, cells have evolved a
dynamic and stress-specific network of molecular chaperones, which maintain a
"healthy" proteome during stress conditions. ATP-independent chaperones
constitute one major class of molecular chaperones, which serve as first-line
defense molecules, protecting against protein aggregation in a stress-dependent
manner. One feature these chaperones have in common is their ability to utilize
structural plasticity for their stress-specific activation, recognition, and
release of the misfolded client. In this paper, we focus on the functional and
structural analysis of one such intrinsically disordered chaperone, the bacterial
redox-regulated Hsp33, which protects proteins against aggregation during
oxidative stress. Here, we present a toolbox of diverse techniques for studying
redox-regulated chaperone activity, as well as for mapping conformational changes
of the chaperone, underlying its activity. Specifically, we describe a workflow
which includes the preparation of fully reduced and fully oxidized proteins,
followed by an analysis of the chaperone anti-aggregation activity in vitro using
light-scattering, focusing on the degree of the anti-aggregation activity and its
kinetics. To overcome frequent outliers accumulated during aggregation assays, we
describe the usage of Kfits, a novel graphical tool which allows easy processing
of kinetic measurements. This tool can be easily applied to other types of
kinetic measurements for removing outliers and fitting kinetic parameters. To
correlate the function with the protein structure, we describe the setup and
workflow of a structural mass spectrometry technique, hydrogen-deuterium exchange
mass spectrometry, that allows the mapping of conformational changes on the
chaperone and substrate during different stages of Hsp33 activity. The same
methodology can be applied to other protein-protein and protein-ligand
interactions.
PMID- 29939187
TI - A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish.
AB - The genetically accessible adult zebrafish (Danio rerio) has been increasingly
used as a vertebrate model for understanding human diseases such as
cardiomyopathy. Because of its convenience and amenability to high throughput
genetic manipulations, the generation of acquired cardiomyopathy models, such as
the doxorubicin-induced cardiomyopathy (DIC) model in adult zebrafish, is opening
the doors to new research avenues, including discovering cardiomyopathy modifiers
via forward genetic screening. Different from the embryonic zebrafish DIC model,
both initial acute and later chronic phases of cardiomyopathy can be determined
in the adult zebrafish DIC model, enabling the study of stage-dependent signaling
mechanisms and therapeutic strategies. However, variable results can be obtained
with the current model, even in the hands of experienced investigators. To
facilitate future implementation of the DIC model, we present a detailed protocol
on how to generate this DIC model in adult zebrafish and describe two alternative
ways of intraperitoneal (IP) injection. We further discuss options on how to
reduce variations to obtain reliable results and provide suggestions on how to
appropriately interpret the results.
PMID- 29939188
TI - Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI
Application in Premanifest Huntington's Disease.
AB - Recent advances in MRI offer a variety of useful markers to identify
neurodegenerative diseases. In Huntington's disease (HD), regional brain atrophy
begins many years prior to the motor onset (during the "premanifest" period), but
the spatiotemporal pattern of regional atrophy across the brain has not been
fully characterized. Here we demonstrate an online cloud-computing platform,
"MRICloud", which provides atlas-based whole-brain segmentation of T1-weighted
images at multiple granularity levels, and thereby, enables us to access the
regional features of brain anatomy. We then describe a regression model that
detects statistically significant inflection points, at which regional brain
atrophy starts to be noticeable, i.e. the "change-point", with respect to a
disease progression index. We used the CAG-age product (CAP) score to index the
disease progression in HD patients. Change-point analysis of the volumetric
measurements from the segmentation pipeline, therefore, provides important
information of the order and pattern of structural atrophy across the brain. The
paper illustrates the use of these techniques on T1-weighted MRI data of
premanifest HD subjects from a large multicenter PREDICT-HD study. This design
potentially has wide applications in a range of neurodegenerative diseases to
investigate the dynamic changes of brain anatomy.
PMID- 29939189
TI - Automated 90Sr Separation and Preconcentration in a Lab-on-Valve System at Ppq
Level.
AB - A quick, automated and portable system for the separation and determination of
radiostrontium in aqueous samples, using Sr-resin and multi sequential flow
injection analysis, has been developed. The concentrations of radioactive
strontium were determined by flow scintillation counting, allowing for on-line
and also on-site determination. The proposed system can determine radioactive
strontium at industrial relevant levels without further modification using
overall analysis time of less than 10 min per aqueous sample. The limit of the
detection is 320 fg.g-1 (1.7 Bq/g).
PMID- 29939190
TI - Quantifying Microglia Morphology from Photomicrographs of Immunohistochemistry
Prepared Tissue Using ImageJ.
AB - Microglia are brain phagocytes that participate in brain homeostasis and
continuously survey their environment for dysfunction, injury, and disease. As
the first responders, microglia have important functions to mitigate neuron and
glia dysfunction, and in this process, they undergo a broad range of morphologic
changes. Microglia morphologies can be categorized descriptively or,
alternatively, can be quantified as a continuous variable for parameters such as
cell ramification, complexity, and shape. While methods for quantifying microglia
are applied to single cells, few techniques apply to multiple microglia in an
entire photomicrograph. The purpose of this method is to quantify multiple and
single cells using readily available ImageJ protocols. This protocol is a summary
of the steps and ImageJ plugins recommended to convert fluorescence and bright
field photomicrographs into representative binary and skeletonized images and to
analyze them using software plugins AnalyzeSkeleton (2D/3D) and FracLac for
morphology data collection. The outputs of these plugins summarize cell
morphology in terms of process endpoints, junctions, and length as well as
complexity, cell shape, and size descriptors. The skeleton analysis protocol
described herein is well suited for a regional analysis of multiple microglia
within an entire photomicrograph or region of interest (ROI) whereas FracLac
provides a complementary individual cell analysis. Combined, the protocol
provides an objective, sensitive, and comprehensive assessment tool that can be
used to stratify between diverse microglia morphologies present in the healthy
and injured brain.
PMID- 29939191
TI - Label-free Neutrophil Enrichment from Patient-derived Airway Secretion Using
Closed-loop Inertial Microfluidics.
AB - Airway secretions contain a large number of immune-related cells, e.g.,
neutrophils, macrophages, and lymphocytes, which can be used as a major resource
to evaluate a variety of pulmonary diseases, both for research and clinical
purposes. However, due to the heterogeneous and viscous nature of patient mucus,
there is currently no reliable dissociation method that does not damage the host
immune cells in the patient airway secretion. In this research, we introduce a
sample preparation method that uses inertial microfluidics for the patient's
immune assessment. Regardless of the heterogeneous fluidic properties of the
clinical samples, the proposed method recovers more than 95% of neutrophils from
airway secretion samples that are diluted 1,000-fold with milliliters of clean
saline. By recirculating the concentrated output stream to the initial sample
reservoir, a high concentration, recovery, and purity of the immune cells are
provided; recirculation is considered a trade-off to the single-run syringe-based
operation of inertial microfluidics. The closed-loop operation of spiral
microfluidics provides leukocytes without physical or chemical disturbance, as
demonstrated by the phorbol 12-myristate 13-acetate (PMA)-induced elastase
release of sorted neutrophils.
PMID- 29939197
TI - Disease classification: from phenotypic similarity to integrative genomics and
beyond.
AB - A fundamental challenge of modern biomedical research is understanding how
diseases that are similar on the phenotypic level are similar on the molecular
level. Integration of various genomic data sets with the traditionally used
phenotypic disease similarity revealed novel genetic and molecular mechanisms and
blurred the distinction between monogenic (Mendelian) and complex diseases.
Network-based medicine has emerged as a complementary approach for identifying
disease-causing genes, genetic mediators, disruptions in the underlying cellular
functions and for drug repositioning. The recent development of machine and deep
learning methods allow for leveraging real-life information about diseases to
refine genetic and phenotypic disease relationships. This review describes the
historical development and recent methodological advancements for studying
disease classification (nosology).
PMID- 29939192
TI - Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand
DNA Breaks by Immunofluorescence Microscopy.
AB - The repair of double-stranded breaks (DSBs) in DNA is a highly coordinated
process, necessitating the formation and resolution of multi-protein repair
complexes. This process is regulated by a myriad of proteins that promote the
association and disassociation of proteins to these lesions. Thanks in large part
to the ability to perform functional screens of a vast library of proteins, there
is a greater appreciation of the genes necessary for the double-strand DNA break
repair. Often knockout or chemical inhibitor screens identify proteins involved
in repair processes by using increased toxicity as a marker for a protein that is
required for DSB repair. Although useful for identifying novel cellular proteins
involved in maintaining genome fidelity, functional analysis requires the
determination of whether the protein of interest promotes localization,
formation, or resolution of repair complexes. The accumulation of repair proteins
can be readily detected as distinct nuclear foci by immunofluorescence
microscopy. Thus, association and disassociation of these proteins at sites of
DNA damage can be accessed by observing these nuclear foci at representative
intervals after the induction of double-strand DNA breaks. This approach can also
identify mis-localized repair factor proteins, if repair defects do not
simultaneously occur with incomplete delays in repair. In this scenario, long
lasting double-strand DNA breaks can be engineered by expressing a rare cutting
endonuclease (e.g., I-SceI) in cells where the recognition site for the said
enzyme has been integrated into the cellular genome. The resulting lesion is
particularly hard to resolve as faithful repair will reintroduce the enzyme's
recognition site, prompting another round of cleavage. As a result, differences
in the kinetics of repair are eliminated. If repair complexes are not formed,
localization has been impeded. This protocol describes the methodology necessary
to identify changes in repair kinetics as well as repair protein localization.
PMID- 29939198
TI - Clinical, genetic and neuropathological characterization of spinocerebellar
ataxia type 37.
AB - The autosomal dominant spinocerebellar ataxias (SCAs) consist of a highly
heterogeneous group of rare movement disorders characterized by progressive
cerebellar ataxia variably associated with ophthalmoplegia, pyramidal and
extrapyramidal signs, dementia, pigmentary retinopathy, seizures, lower motor
neuron signs, or peripheral neuropathy. Over 41 different SCA subtypes have been
described evidencing the high clinical and genetic heterogeneity. We previously
reported a novel spinocerebellar ataxia type subtype, SCA37, linked to an 11-Mb
genomic region on 1p32, in a large Spanish ataxia pedigree characterized by
ataxia and a pure cerebellar syndrome distinctively presenting with early-altered
vertical eye movements. Here we demonstrate the segregation of an unstable
intronic ATTTC pentanucleotide repeat mutation within the 1p32 5' non-coding
regulatory region of the gene encoding the reelin adaptor protein DAB1,
implicated in neuronal migration, as the causative genetic defect of the disease
in four Spanish SCA37 families. We describe the clinical-genetic correlation and
the first SCA37 neuropathological findings caused by dysregulation of cerebellar
DAB1 expression. Post-mortem neuropathology of two patients with SCA37 revealed
severe loss of Purkinje cells with abundant astrogliosis, empty baskets,
occasional axonal spheroids, and hypertrophic fibres by phosphorylated
neurofilament immunostaining in the cerebellar cortex. The remaining cerebellar
Purkinje neurons showed loss of calbindin immunoreactivity, aberrant dendrite
arborization, nuclear pathology including lobulation, irregularity, and
hyperchromatism, and multiple ubiquitinated perisomatic granules immunostained
for DAB1. A subpopulation of Purkinje cells was found ectopically mispositioned
within the cerebellar cortex. No significant neuropathological alterations were
identified in other brain regions in agreement with a pure cerebellar syndrome.
Importantly, we found that the ATTTC repeat mutation dysregulated DAB1 expression
and induced an RNA switch resulting in the upregulation of reelin-DAB1 and
PI3K/AKT signalling in the SCA37 cerebellum. This study reveals the unstable
ATTTC repeat mutation within the DAB1 gene as the underlying genetic cause and
provides evidence of reelin-DAB1 signalling dysregulation in the spinocerebellar
ataxia type 37.
PMID- 29939199
TI - MetaPOAP: Presence or Absence of Metabolic Pathways in Metagenome-Assembled
Genomes.
AB - Summary: Genome-resolved metagenomics allows the construction of draft microbial
genomes from short-read shotgun metagenomics (Metagenome-Assembled Genomes, or
MAGs); however, even high-quality MAGs are typically somewhat incomplete and
contain a small amount of contaminant sequence, making accurate prediction of
metabolic potential challenging. Here we describe MetaPOAP, an algorithm for
probabalistic assessment of the statistical likelihoods for the presence or
absence of metabolic pathways in MAGs. Availability and Implementation: MetaPOAP
is available as a Python script on GitHub or directly from the Fischer lab
webpage. Supplementary information: Example implementation of MetaPOAP is
available as Supplemental Information.
PMID- 29939200
TI - Using multivariate mixed-effects selection models for analyzing batch-processed
proteomics data with non-ignorable missingness.
AB - In quantitative proteomics, mass tag labeling techniques have been widely adopted
in mass spectrometry experiments. These techniques allow peptides (short amino
acid sequences) and proteins from multiple samples of a batch being detected and
quantified in a single experiment, and as such greatly improve the efficiency of
protein profiling. However, the batch-processing of samples also results in
severe batch effects and non-ignorable missing data occurring at the batch level.
Motivated by the breast cancer proteomic data from the Clinical Proteomic Tumor
Analysis Consortium, in this work, we developed two tailored multivariate MIxed
effects SElection models (mvMISE) to jointly analyze multiple correlated
peptides/proteins in labeled proteomics data, considering the batch effects and
the non-ignorable missingness. By taking a multivariate approach, we can borrow
information across multiple peptides of the same protein or multiple proteins
from the same biological pathway, and thus achieve better statistical efficiency
and biological interpretation. These two different models account for different
correlation structures among a group of peptides or proteins. Specifically, to
model multiple peptides from the same protein, we employed a factor-analytic
random effects structure to characterize the high and similar correlations among
peptides. To model biological dependence among multiple proteins in a functional
pathway, we introduced a graphical lasso penalty on the error precision matrix,
and implemented an efficient algorithm based on the alternating direction method
of multipliers. Simulations demonstrated the advantages of the proposed models.
Applying the proposed methods to the motivating data set, we identified
phosphoproteins and biological pathways that showed different activity patterns
in triple negative breast tumors versus other breast tumors. The proposed methods
can also be applied to other high-dimensional multivariate analyses based on
clustered data with or without non-ignorable missingness.
PMID- 29939202
TI - Negative Social Evaluation Impairs Executive Functions in Adolescents With Excess
Weight: Associations With Autonomic Responses.
AB - Background: Adolescents with excess weight suffer social stress more frequently
than their peers with normal weight. Purpose: To examine the impact of social
stress, specifically negative social evaluation, on executive functions in
adolescents with excess weight. We also examined associations between subjective
stress, autonomic reactivity, and executive functioning. Methods: Sixty
adolescents (aged 13-18 years) classified into excess weight or normal weight
groups participated. We assessed executive functioning (working memory,
inhibition, and shifting) and subjective stress levels before and after the Trier
Social Stress Task (TSST). The TSST was divided into two phases according to the
feedback of the audience: positive and negative social evaluation. Heart rate and
skin conductance were recorded. Results: Adolescents with excess weight showed
poorer executive functioning after exposure to TSST compared with adolescents
with normal weight. Subjective stress and autonomic reactivity were also greater
in adolescents with excess weight than adolescents with normal weight. Negative
social evaluation was associated with worse executive functioning and increased
autonomic reactivity in adolescents with excess weight. Conclusions: The findings
suggest that adolescents with excess weight are more sensitive to social stress
triggered by negative evaluations. Social stress elicited deterioration of
executive functioning in adolescents with excess weight. Evoked increases in
subjective stress and autonomic responses predicted decreased executive function.
Deficits in executive skills could reduce cognitive control abilities and lead to
overeating in adolescents with excess weight. Strategies to cope with social
stress to prevent executive deficits could be useful to prevent future obesity in
this population.
PMID- 29939201
TI - Modulation of dietary methionine intake elicits potent, yet distinct, anticancer
effects on primary versus metastatic tumors.
AB - Methionine dependency describes the characteristic rapid in vitro death of most
tumor cells in the absence of methionine. Combining chemotherapy with dietary
methionine deprivation [methionine-deficient diet (MDD)] at tolerable levels has
vast potential in tumor treatment; however, it is limited by MDD-induced toxicity
during extended deprivation. Recent advances in imaging and irradiation delivery
have created the field of stereotactic body radiotherapy (SBRT), where fewer
large-dose fractions delivered in less time result in increased local-tumor
control, which could be maximally synergistic with an MDD short course.
Identification of the lowest effective methionine dietary intake not associated
with toxicity will further enhance the cancer therapy potential. In this study,
we investigated the effects of MDD and methionine-restricted diet (MRD) in
primary and metastatic melanoma models in combination with radiotherapy (RT). In
vitro, MDD dose-dependently sensitized mouse and human melanoma cell lines to RT.
In vivo in mice, MDD substantially potentiated the effects of RT by a significant
delay in tumor growth, in comparison with administering MDD or RT alone. The
antitumor effects of an MDD/RT approach were due to effects on one-carbon
metabolism, resulting in impaired methionine biotransformation via downregulation
of Mat2a, which encodes methionine adenosyltransferase 2A. Furthermore, and
probably most importantly, MDD and MRD substantially diminished metastatic
potential; the antitumor MRD effects were not associated with toxicity to normal
tissue. Our findings suggest that modulation of methionine intake holds
substantial promise for use with short-course SBRT for cancer treatment.
PMID- 29939203
TI - Intronic pentanucleotide TTTCA repeat insertion in the SAMD12 gene causes
familial cortical myoclonic tremor with epilepsy type 1.
AB - Familial cortical myoclonic tremor with epilepsy is an autosomal dominant
neurodegenerative disease, characterized by cortical tremor and epileptic
seizures. Although four subtypes (types 1-4) mapped on different chromosomes
(8q24, 2p11.1-q12.2, 5p15.31-p15.1 and 3q26.32-3q28) have been reported, the
causative gene has not yet been identified. Here, we report the genetic study in
a cohort of 20 Chinese pedigrees with familial cortical myoclonic tremor with
epilepsy. Linkage and haplotype analysis in 11 pedigrees revealed maximum two
point logarithm of the odds (LOD) scores from 1.64 to 3.77 (LOD scores in five
pedigrees were >3.0) in chromosomal region 8q24 and narrowed the candidate region
to an interval of 4.9 Mb. Using whole-genome sequencing, long-range polymerase
chain reaction and repeat-primed polymerase chain reaction, we identified an
intronic pentanucleotide (TTTCA)n insertion in the SAMD12 gene as the cause,
which co-segregated with the disease among the 11 pedigrees mapped on 8q24 and
additional seven unmapped pedigrees. Only two pedigrees did not contain the
(TTTCA)n insertion. Repeat-primed polymerase chain reaction revealed that the
sizes of (TTTCA)n insertion in all affected members were larger than 105 repeats.
The same pentanucleotide insertion (ATTTCATTTC)58 has been reported to form RNA
foci resulting in neurotoxicity in spinocerebellar ataxia type 37, which suggests
the similar pathogenic process in familial cortical myoclonic tremor with
epilepsy type 1.
PMID- 29939204
TI - Landscape of the long non-coding RNA transcriptome in human heart.
AB - Long non-coding RNAs (lncRNAs) have been revealed to play essential roles in the
human cardiovascular system. However, information about their mechanisms is
limited, and a comprehensive view of cardiac lncRNAs is lacking from a multiple
tissues perspective to date. Here, the landscape of the lncRNA transcriptome in
human heart was summarized. We summarized all lncRNA transcripts from publicly
available human transcriptome resources (156 heart samples and 210 samples from
29 other tissues) and systematically analysed all annotated and novel lncRNAs
expressed in heart. A total of 7485 lncRNAs whose expression was elevated in
heart (HE lncRNAs) and 453 lncRNAs expressed in all 30 analysed tissues (EIA
lncRNAs) were extracted. Using various bioinformatics resources, methods and
tools, the features of these lncRNAs were discussed from various perspectives,
including genomic structure, conservation, dynamic variation during heart
development, cis-regulation, differential expression in cardiovascular diseases
and cancers as well as regulation at transcriptional and post-transcriptional
levels. Afterwards, all the features discussed above were integrated into a user
friendly resource named CARDIO-LNCRNAS (http://bio-bigdata.hrbmu.edu.cn/CARDIO
LNCRNAS/ or http://www.bio-bigdata.net/CARDIO-LNCRNAS/). This study represents
the first global view of lncRNAs in the human cardiovascular system based on
multiple tissues and sheds light on the role of lncRNAs in developments and heart
disorders.
PMID- 29939205
TI - Acute inability to mobilise resulting from probable donepezil-induced myoclonus.
AB - Donepezil is a commonly prescribed cholinesterase inhibitor in Alzheimer's
dementia. We present a case of probable donepezil-induced generalised myoclonus
causing total inability to mobilise in a 93-year-old woman.
PMID- 29939206
TI - "Physiological Dysregulation" as Promising Measure of Robustness and Resilience
in Aging Studies and New Indicator of Preclinical Disease.
AB - Recently suggested novel implementation of the statistical distance measure (DM)
for evaluating "physiological dysregulation" (PD) in aging individuals (based on
measuring deviations of multiple biomarkers from baseline/normal physiological
states) allows reducing high-dimensional biomarker space into a single PD
estimate. Here we constructed DM using biomarker profiles from FRAMCOHORT
(Framingham Heart Study) and CHS (Cardiovascular Health Study) Research Materials
obtained from the NHLBI Biologic Specimen and Data Repository Information
Coordinating Center, and estimated effect of PD on total survival, onset of
unhealthy life (proxy for "robustness") and survival following the onset of
unhealthy life (proxy for "resilience"). We investigated relationships between PD
and declines in stress resistance and adaptive capacity not directly observed in
data. PD was more strongly associated with the onset of unhealthy life than with
survival after disease suggesting that declines in robustness and resilience with
age may have overlapping as well as distinct mechanisms. We conclude that
multiple deviations of physiological markers from their normal states (reflected
in higher PD) may contribute to increased vulnerability to many diseases and
precede their clinical manifestation. This supports potential use of PD in health
care as a preclinical indicator of transition from healthy to unhealthy state.
PMID- 29939207
TI - A descriptive marker gene approach to single-cell pseudotime inference.
AB - Motivation: Pseudotime estimation from single-cell gene expression data allows
the recovery of temporal information from otherwise static profiles of individual
cells. Conventional pseudotime inference methods emphasise an unsupervised
transcriptome-wide approach and use retrospective analysis to evaluate the
behaviour of individual genes. However, the resulting trajectories can only be
understood in terms of abstract geometric structures and not in terms of
interpretable models of gene behaviour. Results: Here we introduce an orthogonal
Bayesian approach termed "Ouija" that learns pseudotimes from a small set of
marker genes that might ordinarily be used to retrospectively confirm the
accuracy of unsupervised pseudotime algorithms. Crucially, we model these genes
in terms of switch-like or transient behaviour along the trajectory, allowing us
to understand why the pseudotimes have been inferred and learn informative
parameters about the behaviour of each gene. Since each gene is associated with a
switch or peak time the genes are effectively ordered along with the cells,
allowing each part of the trajectory to be understood in terms of the behaviour
of certain genes. We demonstrate that this small panel of marker genes can
recover pseudotimes that are consistent with those obtained using the entire
transcriptome. Furthermore, we show that our method can detect differences in the
regulation timings between two genes and identify "metastable" states - discrete
cell types along the continuous trajectories - that recapitulate known cell
types. Availability: An open source implementation is available as an R package
at http://www.github.com/kieranrcampbell/ouija and as a Python/TensorFlow package
at http://www.github.com/kieranrcampbell/ouijaflow. Supplementary information:
Supplementary text, figures, and tables are available at Bioinformatics online.
PMID- 29939209
TI - Temporally dependent accelerated failure time model for capturing the impact of
events that alter survival in disease mapping.
AB - The introduction of spatial and temporal frailty parameters in survival models
furnishes a way to represent unmeasured confounding in the outcome of interest.
Using a Bayesian accelerated failure time model, we are able to flexibly explore
a wide range of spatial and temporal options for structuring frailties as well as
examine the benefits of using these different structures in certain settings. A
setting of particular interest for this work involved using temporal frailties to
capture the impact of events of interest on breast cancer survival. Our results
suggest that it is important to include these temporal frailties when there is a
true temporal structure to the outcome and including them when a true temporal
structure is absent does not sacrifice model fit. Additionally, the frailties are
able to correctly recover the truth imposed on simulated data without affecting
the fixed effect estimates. In the case study involving Louisiana breast cancer
specific mortality, the temporal frailty played an important role in representing
the unmeasured confounding related to improvements in knowledge, education, and
disease screenings as well as the impacts of Hurricane Katrina and the passing of
the Affordable Care Act. In conclusion, the incorporation of temporal, in
addition to spatial, frailties in survival analysis can lead to better fitting
models and improved inference by representing both spatially and temporally
varying unmeasured risk factors and confounding that could impact survival.
Specifically, we successfully estimated changes in survival around the time of
events of interest.
PMID- 29939210
TI - SOPanG: online text searching over a pan-genome.
AB - Motivation: The many thousands of high-quality genomes available nowadays imply a
shift from single genome to pan-genomic analyses. A basic algorithmic building
brick for such a scenario is online search over a collection of similar texts, a
problem with surprisingly few solutions presented so far. Results: We present
SOPanG, a simple tool for exact pattern matching over an elastic-degenerate
string, a recently proposed simplified model for the pan-genome. Thanks to bit
parallelism, it achieves pattern matching speeds above 400MB/s, more than an
order of magnitude higher than of other software. Availability: SOPanG is
available for free from: https://github.com/MrAlexSee/sopang. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29939208
TI - Impacts of older people's patient and public involvement in health and social
care research: a systematic review.
AB - Background: patient and public involvement (PPI) in research has been linked with
numerous beneficial impacts, however, evidence for older people's involvement is
limited. Objectives: to evaluate the impacts of involving older people in health
and social care research on older co-researchers, academic researchers, and
research processes and outcomes. A secondary aim was to explore critical success
factors and future considerations for PPI. Design: systematic review. Methods:
six databases were searched for English language articles published between 2006
and 2017. A supplementary search was conducted. Two authors independently
retrieved articles using standardised inclusion criteria and data extraction
forms. Articles reporting formal evaluation of older people's involvement were
included. Results: nine articles, all using qualitative methodology, were
included. Benefits for older co-researchers included psychological and social
benefits, new learning, and activism and career opportunities, while challenging
impacts comprised demanding workloads, difficult relationships and
dissatisfaction with level of involvement. Benefits for academic researchers
entailed new learning and shared workloads; challenges related to demanding
workloads and difficult relationships. Both positive and negative effects on
research quality and impact were observed. Benefits for participants and the
community were demonstrated. Building relationships, facilitating communication
and breaking down barriers to participation were identified as critical success
factors. Conclusions: evidence for the impacts of older people's involvement is
mixed although benefits appear to outweigh the challenges. Future considerations
for PPI include matching older people's skills and motivations to the project and
level of involvement, and establishing an iterative research process in which
evaluation is embedded.
PMID- 29939211
TI - Left temporal lobe language network connectivity in temporal lobe epilepsy.
AB - Impairment of naming function is a critical problem for temporal lobe epilepsy
patients, yet the neural correlates of the disruption of temporal lobe language
networks are poorly understood. Using functional MRI, we investigated the
activation and task-related functional connectivity of left temporal lobe
language networks and their relation to clinical naming performance and disease
characteristics. We studied 59 adult patients with temporal lobe epilepsy (35
left temporal lobe epilepsy) and 32 healthy controls with auditory and visual
naming functional MRI tasks. Time series of activation maxima in the left
posterior inferior temporal lobe were extracted to create a psychophysiological
interaction regressor for subsequent seed-based whole-brain task-related
functional connectivity analyses. Correlational analyses were performed to assess
the association of functional MRI activation and functional connectivity with
clinical naming scores, age of onset of epilepsy, and duration of epilepsy.
Auditory naming elicited activation in the left posterior inferior temporal gyrus
and visual naming in the left fusiform gyrus across all groups. Activations in
the left inferior temporal gyrus, left thalamus and left supplementary motor
region during auditory naming as well as left fusiform activations during picture
naming correlated with better clinical naming performance. Functional
connectivity analyses indicated coupling of left posterior inferior temporal
regions to bilateral anterior and posterior temporal lobe regions and the
bilateral inferior precentral gyrus as well as contralateral occipital cortex.
Stronger functional connectivity was associated with better clinical naming
performance in all groups. In patients with left temporal lobe epilepsy only,
functional connectivity increased with later age of onset of epilepsy and shorter
disease duration. This suggests that onset of seizures early in life and
prolonged disease duration lead to disrupted recruitment of temporal lobe
networks ipsilateral to the seizure focus, which might account for naming
deficits in temporal lobe epilepsy.
PMID- 29939212
TI - Zero-inflated generalized Dirichlet multinomial regression model for microbiome
compositional data analysis.
AB - There is heightened interest in using high-throughput sequencing technologies to
quantify abundances of microbial taxa and linking the abundance to human diseases
and traits. Proper modeling of multivariate taxon counts is essential to the
power of detecting this association. Existing models are limited in handling
excessive zero observations in taxon counts and in flexibly accommodating complex
correlation structures and dispersion patterns among taxa. In this article, we
develop a new probability distribution, zero-inflated generalized Dirichlet
multinomial (ZIGDM), that overcomes these limitations in modeling multivariate
taxon counts. Based on this distribution, we propose a ZIGDM regression model to
link microbial abundances to covariates (e.g. disease status) and develop a fast
expectation-maximization algorithm to efficiently estimate parameters in the
model. The derived tests enable us to reveal rich patterns of variation in
microbial compositions including differential mean and dispersion. The advantages
of the proposed methods are demonstrated through simulation studies and an
analysis of a gut microbiome dataset.
PMID- 29939213
TI - runibic: a Bioconductor package for parallel row-based biclustering of gene
expression data.
AB - Motivation: Biclustering is an unsupervised technique of simultaneous clustering
of rows and columns of input matrix. With multiple biclustering algorithms
proposed, UniBic remains one of the most accurate methods developed so far.
Results: In this paper we introduce a Bioconductor package called runibic with
parallel implementation of UniBic. For the convenience the algorithm was
reimplemented, parallelized, and wrapped within an R package called runibic. The
package includes: (1) a couple of times faster parallel version of the original
sequential algorithm, (2) much more efficient memory management, (3) modularity
which allows to build new methods on top of the provided one, and (4) integration
with the modern Bioconductor packages such as SummarizedExperiment, ExpressionSet
and biclust. Availability: The package is implemented inR(3.4) and is available
from Bioconductor (3.6) at the following URL
http://bioconductor.org/packages/runibic with installation instructions and
tutorial. Supplementary information: Supplementary informations are available in
vignette of the package.
PMID- 29939214
TI - Depressive Symptoms and their Relation to Age and Chronic diseases among middle
aged and Older Adults in rural South Africa.
AB - Background: Understanding how depression is associated with chronic conditions
and socio-demographic characteristics can inform the design and effective
targeting of depression screening and care interventions. In this study, we
present some of the first evidence from sub-Saharan Africa on the association
between depressive symptoms and a range of chronic conditions (diabetes, HIV,
hypertension, and obesity) as well as socio-demographic characteristics. Methods:
A questionnaire was administered to a population-based simple random sample of
5,059 adults aged 40 years in Agincourt, South Africa. Depressive symptoms were
measured using a modified version of the eight-item Center for Epidemiological
Studies Depression screening tool. Diabetes was assessed using a capillary blood
glucose measurement and HIV using a dried blood spot. Results: 17.0% (95% CI:
15.9% - 18.1%) of participants had at least three depressive symptoms. None of
the chronic conditions were significantly associated with depressive symptoms in
multivariable regressions. Older age was the strongest correlate of depressive
symptoms with those aged 80 years and older having on average 0.63 (95% CI: 0.40
0.86; p<0.001) more depressive symptoms than those aged 40-49 years. Household
wealth quintile and education were not significant correlates. Conclusions: This
study provides some evidence that the positive associations of depression with
diabetes, HIV, hypertension, and obesity that are commonly reported in high
income settings might not exist in rural South Africa. Our finding that
increasing age is strongly associated with depressive symptoms suggests that
there is a particularly high need for depression screening and treatment among
the elderly in rural South Africa.
PMID- 29939215
TI - Versatile interactions and bioinformatics analysis of noncoding RNAs.
AB - Advances in RNA sequencing technologies and computational methodologies have
provided a huge impetus to noncoding RNA (ncRNA) study. Once regarded as
inconsequential results of transcriptional promiscuity, ncRNAs were later found
to exert great roles in various aspects of biological functions. They are
emerging as key players in gene regulatory networks by interacting with other
biomolecules (DNA, RNA or protein). Here, we provide an overview of ncRNA
repertoire and highlight recent discoveries of their versatile interactions. To
better investigate the ncRNA-mediated regulation, it is necessary to make full
use of innovative sequencing techniques and computational tools. We further
describe a comprehensive workflow for in silico ncRNA analysis, providing up-to
date platforms, databases and tools dedicated to ncRNA identification and
functional annotation.
PMID- 29939216
TI - A Prospective Pilot Study Comparing Rate of Processing Techniques in Autologous
Fat Grafting.
AB - Background: Autologous fat grafting (AFG) is increasing in popularity to address
a variety of defects. There is interest in developing techniques to harvest,
process and inject fat to improve clinical outcomes as well as operative
efficiency. Objectives: The purpose of this pilot study is to compare the rate of
graft processing of two commercially available systems for graft preparation.
Methods: Twenty consecutive cases using an active filtration system-AF were
observed followed by twenty consecutive cases using a passive filtration system
PF to compare efficiency rate. Fat processing rate was quantified in
milliliters/minute. Results: Forty patients underwent autologous fat grafting
with no differences in patient characteristics between the groups. There was one
incidence of palpable fat necrosis per group (5%). For all patients, this was the
first fat grafting procedure; 20% of patients (n=4 per group) had additional fat
grafting. Overall, the rate of adipose tissue preparation was significantly
higher with the active system-AF compared to the passive system-PF (19.8 ml/min
vs 5.3 ml/min, p <=0.001). The resulting percent of graftable fat was comparable
(AF: 41% vs. PF: 42%; p=0.83). Conclusions: Time and motion studies such as this
provide a means to systematically document each of the steps involved in fat
grafting in a reliable fashion. The authors demonstrate significantly higher rate
of lipoaspirate processing using an active filtration system compared to a
passive system. Further large-scale studies of the efficacy and cost analysis of
autologous fat grafting are a necessary component of determining best practices
in the field.
PMID- 29939217
TI - Practical Dynamic de Bruijn Graphs.
AB - Motivation: The de Bruijn graph is fundamental to the analysis of next generation
sequencing data and so, as datasets of DNA reads grow rapidly, it becomes more
important to represent de Bruijn graphs compactly while still supporting fast
assembly. Previous implementations of compact de Bruijn graphs have not supported
node or edge deletion, however, which is important for pruning spurious elements
from the graph. Results: Belazzougui et al. (2016b) recently proposed a compact
and fully dynamic representation, which supports exact membership queries and
insertions and deletions of both nodes and edges. In this paper, we give a
practical implementation of their data structure, supporting exact membership
queries and fully dynamic edge operations, as well as limited support for dynamic
node operations. We demonstrate experimentally that its performance is comparable
to that of state-of-the-art implementations based on Bloom filters. Availability
and Implementation: Our source-code is publicly available at
https://github.com/csirac/dynamicDBG under an open-source license.
PMID- 29939218
TI - rs401681 and rs402710 confer lung cancer susceptibility by regulating TERT
expression instead of CLPTM1L in East Asian populations.
AB - Lung cancer is a common cancer in human and has presented significant genetic
predisposition. Previous genome-wide association study observed that rs401681
within CLPTM1L (CLPTM1 like) was significantly associated with lung cancer. By
analyzing 1000 genomes data for East Asian, we identified only one SNP in nearby
region, rs402710, in high linkage disequilibrium with rs401681, which was also
associated with lung cancer. However, the real causal SNP and mechanism for the
association were still not clear. The following plasmid construction,
mutagenesis, transient transfection and luciferase reading indicated that both
SNPs could regulate gene expression in lung/bronchial epithelium Beas-2B cell
line. By chromosome conformation capture, it was identified that the segment
containing these two SNPs could interact with TERT (telomerase reverse
transcriptase) promoter, thus indicating that these SNPs confer lung cancer risk
by regulating TERT expression instead of CLPTM1L. Through chromatin
immunoprecipitation, the transcript factors HNF4A (hepatocyte nuclear factor 4
alpha) and MAF1 (MAF1 homolog, negative regulator of RNA polymerase III) were
recognized for the regions spanning rs401681 and rs402710, respectively. Our
results uncovered a complete link between these two SNPs and lung cancer.
PMID- 29939220
TI - Erratum to: Minimal shortening of leukocyte telomere length across age groups in
a cross-sectional study for carriers of a longevity-associated FOXO3 allele.
PMID- 29939219
TI - Robust clustering of noisy high-dimensional gene expression data for patients
subtyping.
AB - Motivation: One of the most important research areas in personalized medicine is
the discovery of disease sub-types with relevance in clinical applications. This
is usually accomplished by exploring gene expression data with unsupervised
clustering methodologies. Then, with the advent of multiple omics technologies,
data integration methodologies have been further developed to obtain better
performances in patient separability. However, these methods do not guarantee the
survival separability of the patients in different clusters. Results: We propose
a new methodology that first computes a robust and sparse correlation matrix of
the genes, then decomposes it and projects the patient data onto the first m
spectral components of the correlation matrix. After that, a robust and adaptive
to noise clustering algorithm is applied. The clustering is set up to optimize
the separation between survival curves estimated cluster-wise. The method is able
to identify clusters that have different omics signatures and also statistically
significant differences in survival time. The proposed methodology is tested on
five cancer datasets downloaded from The Cancer Genome Atlas repository. The
proposed method is compared with the Similarity Network Fusion (SNF) approach,
and model based clustering based on Student's t-distribution (TMIX). Our method
obtains a better performance in terms of survival separability, even if it uses a
single gene expression view compared to the multi-view approach of the SNF
method. Finally, a pathway based analysis is accomplished to highlight the
biological processes that differentiate the obtained patient groups. Availability
and implementation: Our R source code is available online at
https://github.com/angy89/RobustClusteringPatientSubtyping. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29939222
TI - Tightly Integrated Genomic and Epigenomic Data Mining Using Tensor Decomposition.
AB - Motivation: Complex diseases such as cancers often involve multiple types of
genomic and/or epigenomic abnormalities. Rapid accumulation of multiple types of
omics data demands methods for integrating the multidimensional data in order to
elucidate complex relationships among different types of genomic and epigenomic
abnormalities. Results: In the present study, we propose a tightly integrated
approach based on tensor decomposition. Multiple types of data, including mRNA,
methylation, copy number variations, and somatic mutations, are merged into a
high-order tensor which is used to develop predictive models for overall
survival. The weight tensors of the models are constrained using
CANDECOMP/PARAFAC (CP) tensor decomposition and learned using support tensor
machine regression (STR) and ridge tensor regression (RTR). The results
demonstrate that the tensor decomposition based approaches can achieve better
performance than the models based individual data type and the concatenation
approach. Availability: N/A. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29939221
TI - Abeta inhibits mesenchymal stem cell-pericyte transition through MAPK pathway.
AB - Multiple independent reports have demonstrated pericyte loss in both the
hippocampus and cortex in human Alzheimer's disease (AD). The differentiation and
recruitment of pericytes are the essential steps in vasculature development.
However, the role of amyloid beta (Abeta) in pericyte differentiation has not yet
been fully elucidated. In this study, we investigated the interaction between
Abeta and differentiation of mesenchymal stem cells (MSCs) toward pericytes in
culture. Our results showed that mice overexpressing Abeta-precursor protein
(APP/PS1) exhibited the loss of pericytes compared with the control group mice,
evidenced by the lack of desmin expression in the cortex of 12-month-old mice.
Interestingly, we further found that both Abeta40 and Abeta42 inhibited the
expressions of pericyte markers (alpha-SMA, desmin, and PDGFRbeta) in cultured
MSCs which can be differentiated into mature pericytes. Mechanistically, the
inhibitory effects of Abetas on MSC-pericyte transition is mediated by the
activation of the ERK1/2 MAPK signal pathway. These new insights into the roles
of Abeta in pericyte differentiation may help to develop more effective
strategies for the treatment of AD.
PMID- 29939223
TI - Unravelling immune cell complexity in atherosclerosis.
PMID- 29939224
TI - Contribution of BKCa channels to vascular tone regulation by PDE3 and PDE4 is
lost in heart failure.
AB - Aims: Regulation of vascular tone by 3',5'-cyclic adenosine monophosphate (cAMP)
involves many effectors, including the large conductance, Ca2+-activated, K+
(BKCa) channels. In arteries, cAMP is mainly hydrolyzed by type 3 and 4
phosphodiesterases (PDE3, PDE4). Here, we examined the specific contribution of
BKCa channels to tone regulation by these PDEs in rat coronary arteries, and how
this is altered in heart failure. Methods and Results: Concomitant application of
PDE3 (cilostamide) and PDE4 (Ro-20-1724) inhibitors increased BKCa unitary
channel activity in isolated myocytes from rat coronary arteries. Myography was
conducted in isolated, U46619-contracted coronary arteries. Cilostamide or Ro-20
1724 induced a vasorelaxation that was greatly reduced by iberiotoxin, a BKCa
channel blocker. Ro-20-1724 and cilostamide potentiated the relaxation induced by
the beta-adrenergic agonist isoprenaline or the adenylyl cyclase activator L
858051. Iberiotoxin abolished the effect of PDE inhibitors on isoprenaline but
did not on L-858051. In coronary arteries from rats with heart failure induced by
aortic stenosis, contractility and response to acetylcholine were dramatically
reduced compared to arteries from sham rats, but relaxation to PDE inhibitors was
retained. Interestingly, however, iberiotoxin had no effect on Ro-20-1724- and
cilostamide-induced vasorelaxations in heart failure. Expression of the BKCa
channel alpha-subunit, of a 98 kDa PDE3A and of a 80 kDa PDE4D were lower in
heart failure compared to sham coronary arteries while that of a 70 kDa PDE4B was
increased. Proximity ligation assays demonstrated that PDE3 and PDE4 were
localized in the vicinity of the channel. Conclusion: BKCa channels mediate the
relaxation of coronary artery induced by PDE3 and PDE4 inhibition. This is
achieved by co-localization of both PDEs with BKCa channels, enabling tight
control of cAMP available for channel opening. Contribution of the channel is
prominent at rest and on beta-adrenergic stimulation. This coupling is lost in
heart failure.
PMID- 29939225
TI - CD1d-dependent natural killer T cells attenuate angiotensin II-induced cardiac
remodeling via IL-10 signaling in mice.
AB - Aims: Cd1d is a member of the cluster of differentiation 1 (CD1) family of
glycoproteins expressed on the surface of various antigen-presenting cells, which
is recognized by natural killer T (NKT) cells. CD1d-dependent NKT cells play an
important role in immune-mediated diseases; but the role of these cells in
regulating cardiac remodeling remains unknown. Methods and Results: Cardiac
remodeling was induced by angiotensin (Ang) II infusion for 2 weeks. Ang II
induced increase in hypertension, cardiac performance, hypertrophy and fibrosis,
inflammatory response and activation of the NF-kB and TGF-beta1/Smad2/3 pathways
was significantly aggravated in CD1d knockout (CD1dko) mice compared with wild
type (WT) mice, but these effects were markedly abrogated in WT mice treated with
alpha-galactosylceramide (alphaGC), a specific activator of NKT cells. Adoptive
transfer of CD1dko bone marrow cells to WT mice further confirmed the deleterious
effect of CD1d knockout. Moreover, IL-10 expression was significantly decreased
in CD1dko hearts but increased in alphaGC-treated mice. Co-culture experiments
revealed that CD1dko dentritic cells (DCs) significantly reduced IL-10 mRNA
expression from NKT cells. Administration of recombinant murine IL-10 to CD1dko
mice improved hypertension, cardiac performance and adverse cardiac remodeling
induced by Ang II, and its cardioprotective effect was possibly associated with
activation of STAT3, and inhibition of the TGF-beta1 and NF-kB pathways.
Conclusion: These findings revealed a previously undefined role for CD1d
dependent NKT cells in Ang II-induced cardiac remodeling, hence activation of NKT
cells may be a novel therapeutic target for hypertensive cardiac disease.
PMID- 29939226
TI - Chinese Women's Drinking Patterns Before and After the Hong Kong Alcohol Policy
Changes.
AB - Aims: To examine the patterns of alcohol consumption in Hong Kong Chinese women
before and after a period of major alcohol policy amendments. Short summary: This
study compared alcohol consumption patterns in Hong Kong Chinese women before and
after a period of major alcohol policy amendments and found increased drinking
among certain subgroups, particularly middle-aged women. These increases are
likely due to personal factors (e.g. changing perceptions) as well as
environmental influences (e.g. greater marketing). Methods: Cross-sectional
telephone surveys were conducted on adult Chinese women prior to the 2007-2008
beer and wine tax eliminations in 2006 (n = 4946) and in 2011 (n = 2439).
Results: Over the study period, only women in the 36-45 year age stratum reported
significant increases in all three drinking patterns: past-year drinking (38.1
45.2%), past-month binge drinking (2.3-5.2%) and weekly drinking (4.0-7.3%) (P <
0.05); middle-aged women, unemployed or retired women and those ascribing to
alcohol's health benefits emerged as new binge drinking risk groups. In 2011,
3.5% of all drinking-aged women (8.8% of past-year drinkers, 20.7% of binge
drinkers and 23.1% of weekly drinkers) reported an increased drinking frequency
after the tax policy changes. The main contexts of increased drinking were social
events and with restaurant meals; moreover, beliefs of alcohol's health benefits
were common to all contexts of increased drinking. Of women who increased their
drinking frequency, the largest proportion attributed it to peer effects/social
environment conducive to drinking, and brand marketing/advertising influences.
Conclusions: Increased drinking among certain subgroups of Hong Kong Chinese
women may be due to combined influences of: increased societal acceptance of
social drinking, aggressive marketing promotions and personal beliefs in the
health benefits of drinking that have recently emerged in the region. Hence,
multi-prong strategies are required to combat potential drinking harms in these
women.
PMID- 29939227
TI - Predicting miRNA-disease association based on inductive matrix completion.
AB - Motivation: It has been shown that microRNAs (miRNAs) play key roles in variety
of biological processes associated with human diseases. In Consideration of the
cost and complexity of biological experiments, computational methods for
predicting potential associations between miRNAs and diseases would be an
effective complement. Results: This paper presents a novel model of Inductive
Matrix Completion for MiRNA-Disease Association prediction (IMCMDA). The
integrated miRNA similarity and disease similarity are calculated based on miRNA
functional similarity, disease semantic similarity and Gaussian interaction
profile kernel similarity. The main idea is to complete the missing miRNA-disease
association based on the known associations and the integrated miRNA similarity
and disease similarity. IMCMDA achieves AUC of 0.8034 based on leave-one-out
cross-validation and improved previous models. In addition, IMCMDA was applied to
five common human diseases in three types of case studies. In the first type,
respectively, 42, 44, 45 out of top 50 predicted miRNAs of Colon Neoplasms,
Kidney Neoplasms, Lymphoma were confirmed by experimental reports. In the second
type of case study for new diseases without any known miRNAs, we chose Breast
Neoplasms as the test example by hiding the association information between the
miRNAs and Breast Neoplasms. As a result, 50 out of top 50 predicted Breast
Neoplasms-related miRNAs are verified. In the third type of case study, IMCMDA
was tested on HMDD V1.0 to assess the robustness of IMCMDA, 49 out of top 50
predicted Esophageal Neoplasms-related miRNAs are verified. Availability: The
code and dataset of IMCMDA are freely available at
https://github.com/IMCMDAsourcecode/IMCMDA. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29939228
TI - Temporal Transcriptomic Analysis of Metabolic Genes in Maternal Organs and
Placenta During Murine Pregnancy.
AB - Maternal pregnancy adaptation is crucial for fetal development and long-term
health. Complex interactions occur between maternal digestive and excretory
systems as they interface with the developing fetus through the placenta, and
transcriptomic regulation in these organs throughout pregnancy is poorly
understood. Our objective is to characterize transcriptomic changes across
gestation in maternal organs and placenta. Gene expression was quantified in the
kidney, liver and small intestine harvested from non-pregnant and pregnant FVB
mice at 4 time points and placenta at 3 time points (N = 5/time point) using
Affymetrix Mouse Gene 1.0 ST arrays. In maternal organs, we identified 476 genes
in the liver, 207 genes in the kidney, and 27 genes in the small intestine that
were differentially expressed across gestation (FDR adjusted q < 0.05). The
placenta had a total of 1576 differentially expressed genes between the placenta
at either/gd15 or gd19 compared to gd10. We identified a number of pathways
enriched for genes differentially expressed across gestation, including 5
pathways in the placenta, 9 pathways in the kidney, and 28 pathways in the liver,
including the citrate cycle, retinol metabolism, bile acid synthesis and steroid
bile synthesis, which play functional roles in fetal development and pregnancy
maintenance. Characterization of normal longitudinal changes that occur in
pregnancy, provides context to understand how perturbations in these biochemical
pathways and perturbations in nutrient signaling may impact pregnancy.
PMID- 29939229
TI - Comparison of endoscopic vacuum therapy versus endoscopic stenting for esophageal
leaks: systematic review and meta-analysis.
AB - Esophageal leaks remain a life-threatening postoperative complication of
esophagectomy. Currently, self-expanding metal stents (SEMS) represent the
endoscopic mainstay of treatment. Recently, endoscopic vacuum therapy (EVT) has
emerged and shown promising results in these patients. We conducted an electronic
systematic search using MEDLINE databases (PubMed, EMBASE, and Web of Science)
looking for studies comparing EVT and SEMS for the treatment of esophageal leak
and/or perforation. Four studies including 163 patients matched the inclusion
criteria. Esophageal leak closure rate is significantly higher with EVT than SEMS
[pooled odds ratio 5.51 (95% CI 2.11-14.88; P < 0.001)]. Additionally, EVT has a
shorter treatment duration [pooled mean difference -9.0 days (95% CI 16.6-1.4; P
= 0.021)], lower major complication (P = 0.011), and in-hospital mortality (P =
0.002) rate compared to SEMS. EVT for esophageal leak is feasible and safe. It
has the potential to become the new gold standard in the endoscopic treatment of
esophageal leaks and perforations. However, further comparative studies with SEMS
are needed to strengthen the current evidence.
PMID- 29939230
TI - Predictors of dropout in the school-based multi-component intervention, 'Mexa
se'.
AB - To identify the predictors of dropout in the 'Mexa-se' intervention according to
the body mass index (BMI) category. This was a controlled, non-randomized study.
The intervention included: (i) increase in the intensity of physical activities
(PA) in physical education (PE) classes; (ii) active recess; (iii) educational
sessions on PA, nutrition and body image; and (iv) educational materials. Dropout
was considered when students dropped out of intervention, or did not reach 75%
attendance in PE classes. The independent variables were gender, age, study
period, socioeconomic status, BMI, PA, screen time, food consumption, health
perception, attitudes toward PA, self-efficacy for PA, perception of the school
environment, body image and self-esteem. Binary logistic regression analysis was
used. The dropout rate was 26.8%. In the total sample and among students with an
adequate BMI, there was a greater probability of dropout with an increase in age.
For overweight students, increased age and socioeconomic status, and studying in
the afternoon period were predictors of dropout from the intervention. Socio
demographic factors were predictors of dropout from the 'Mexa-se' intervention;
the associated factors differed based on the BMI category.
PMID- 29939231
TI - Histological Risk Factors to Predict Clinical Relapse in Ulcerative Colitis With
Endoscopically Normal Mucosa.
AB - Background and Aims: The current goal of treatment for ulcerative colitis [UC] is
endoscopic and ultimately histological mucosal healing. However, there is no
consensus on the definition of histological mucosal healing. We evaluated
histological risk factors for clinical relapse in UC patients with endoscopically
normal mucosa to focus on the importance of histological evaluation. Methods :
Patients with UC who underwent colonoscopy confirming Mayo endoscopic subscore
[MES] <= 1 with biopsies were enrolled into this retrospective cohort. Three
expert pathologists evaluated the presence or absence of chronic inflammatory
cell infiltrate, breaches in the surface epithelium, crypt abscesses, mucin
depletion, crypt architectural irregularities and basal plasmacytosis. Clinical
relapse was defined as partial Mayo score >= 3 or modification of induction
treatment. Prediction models of clinical relapse were generated, especially in
patients with MES 0. Results: A total of 194 UC patients were enrolled.
Histological abnormalities existed more frequently in patients with MES 1 than
those with MES 0, while the vast majority of patients still possessed at least
one abnormality. There was no significant difference in time to relapse between
MES 0 and 1. Crypt architectural irregularities and mucin depletion were
associated with time to relapse in patients with MES <= 1. In patients with MES
0, the presence of mucin depletion was the only factor significantly and
independently associated with the risk of relapse (hazard ratio, 2.18 [1.16
5.82]; p = 0.03). Conclusions: Mucin depletion was shown to be a histological
risk factor for clinical relapse in UC patients with MES 0.
PMID- 29939232
TI - Structural and functional analysis of Alg1 beta-1,4 mannosyltransferase reveals
the physiological importance of its membrane topology.
AB - In eukaryotes, the biosynthesis of a highly conserved dolichol-linked
oligosaccharide (DLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol)
begins on the cytoplasmic face of the endoplasmic reticulum (ER) and ends within
the lumen. Two functionally distinguished heteromeric glycosyltransferase (GTase)
complexes are responsible for the cytosolic DLO assembly. Alg1, a beta-1, 4
mannosyltransferase (MTase) physically interacts with Alg2 and Alg11 proteins to
form the multienzyme complex which catalyzes the addition of all five mannose to
generate the Man5GlcNAc2-PP-Dol intermediate. Despite the fact that Alg1 plays a
central role in the formation of the multi-MTase has been confirmed, the
topological information of Alg1 including the molecular mechanism of membrane
association are still poorly understood. Using a combination of bioinformatics
and biological approaches, we have undertaken a structural and functional study
on Alg1 protein, in which the enzymatic activities of Alg1 and its variants were
monitored by a complementation assay using the GALpr-ALG1 yeast strain, and
further confirmed by a liquid chromatography-mass spectrometry-based in vitro
quantitative assay. Computational and experimental evidence confirmed Alg1 shares
structure similarity with Alg13/14 complex, which has been defined as a membrane
associated GT-B GTase. Particularly, we provide clear evidence that the N
terminal transmembrane domain including the following positively charged amino
acids and an N-terminal amphiphilic-like alpha helix domain exposed on the
protein surface strictly coordinate the Alg1 orientation on the ER membrane. This
work provides detailed membrane topology of Alg1 and further reveals its
biological importance at the spatial aspect in coordination of cytosolic DLO
biosynthesis.
PMID- 29939233
TI - Blank Canvas: The Case for Descriptive Taxonomy.
AB - Describing species is fundamental to understanding the biosphere and the origins
of biodiversity. Without descriptions, we miss many of the most improbable,
interesting, and informative aspects of species, higher taxa, and evolutionary
history. Further, descriptive taxonomy opens a treasure trove of nature-inspired
solutions for creating a sustainable future.
PMID- 29939234
TI - Primary Care Physicians' Perceived Barriers to Optimal Dementia Care: A
Systematic Review.
AB - Background and Objectives: Primary care physicians (PCPs) have a key role in
providing care for people with dementia and their carers, however, a range of
barriers prevent them from delivering optimal care. We reviewed studies on PCPs'
perceptions of barriers to providing optimal dementia care, including their
methodological quality, whether they focused on barriers related to diagnosis
and/or management, and the patient-, provider-, and system-level barriers
identified. Research Design and Methods: Studies were included if they were
quantitative studies published since 2006 which reported on PCPs' perceptions of
the barriers to providing dementia care. The methodological quality of identified
studies was assessed using an adapted version of accepted rating criteria for
quantitative studies. Data were extracted from studies which were rated as
"moderate" or "strong" quality. Results: A total of 20 studies were identified,
16 of which were rated as "moderate" or "strong" methodological quality. Patient
related barriers included a reluctance to acknowledge cognitive decline and
patient nonadherence to management plans. Provider-related barriers included a
lack of training and confidence. System-related barriers included a lack of time
during consultations and lack of support services. Discussion and Implications:
This review highlights a range of barriers to dementia diagnosis and management
from studies rated as being methodologically adequate. Future studies should also
utilize theory-driven approaches to exploring a comprehensive range of barriers
to optimal dementia care across the care trajectory.
PMID- 29939235
TI - Reply to 'Comment on Sarcopenia is a Novel Predictor of the Need for Rescue
Therapy in Hospitalized Ulcerative Colitis Patients'.
PMID- 29939237
TI - Questioning the obvious: does dyspnoea really matter in heart failure?
PMID- 29939239
TI - Implementing alcohol screening and brief interventions in primary health care:
study protocol for a pilot cluster randomized controlled trial.
AB - Background: Alcohol is one of the most important risk factors contributing to the
global burden of disease. Screening and brief interventions in primary care
settings are effective in reducing alcohol consumption. However, implementation
of such interventions in routine practice has been proven difficult. Most
programmes in practice and research have lacked a theoretical rationale for how
they would change practitioner behaviour. Objective: To determine whether a
theory-based behaviour change intervention delivered to primary care practices
significantly increases delivery of alcohol screening. Methods: We will conduct a
two-arm, cluster-randomized controlled, parallel, open trial. Twelve primary care
practices will be randomized to one of two groups: training and support; and
waiting-list control. Family physicians, nurses and receptionists will be
eligible to participate. The intervention will be a training and support
programme. The intervention will be tailored to the barriers and facilitators for
implementing alcohol screening and brief interventions following the principles
of the Behaviour Change Wheel approach. The primary outcome will be the
proportion of patients screened with the Alcohol Use Disorders Identification
Test. Conclusion: This study will test whether a theory-driven implementation
programme increases alcohol screening rates in primary care. Results from this
trial will provide a useful addition to existing evidence by informing
implementation researchers what areas of behaviour change are critical to
increasing alcohol screening rates. Trial registration: clinicaltrials.gov
NCT02968186.
PMID- 29939236
TI - Corpus Callosum White Matter Diffusivity Reflects Cumulative Neurological
Comorbidity in Tuberous Sclerosis Complex.
AB - INTRODUCTION: Neurological manifestations in Tuberous Sclerosis Complex (TSC) are
highly variable. Diffusion tensor imaging (DTI) may reflect the neurological
disease burden. We analyzed the association of autism spectrum disorder (ASD),
intellectual disability (ID) and epilepsy with callosal DTI metrics in subjects
with and without TSC. METHODS: 186 children underwent 3T MRI DTI: 51 with TSC (19
with concurrent ASD), 46 with non-syndromic ASD and 89 healthy controls (HC).
Subgroups were based on presence of TSC, ASD, ID, and epilepsy. Density-weighted
DTI metrics obtained from tractography of the corpus callosum were fitted using a
2-parameter growth model. We estimated distributions using bootstrapping and
calculated half-life and asymptote of the fitted curves. RESULTS: TSC was
associated with a lower callosal fractional anisotropy (FA) than ASD, and ASD
with a lower FA than HC. ID, epilepsy and ASD diagnosis were each associated with
lower FA values, demonstrating additive effects. In TSC, the largest change in FA
was related to a comorbid diagnosis of ASD. Mean diffusivity (MD) showed an
inverse relationship to FA. Some subgroups were too small for reliable data
fitting. CONCLUSIONS: Using a cross-disorder approach, this study demonstrates
cumulative abnormality of callosal white matter diffusion with increasing
neurological comorbidity.
PMID- 29939240
TI - Interaction Between Linepithema micans (Hymenoptera: Formicidae) and the Vine
Mealybug Planococcus ficus (Hemiptera: Pseudococcidae): Trophobiosis or
Predation?
AB - The mealybug Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae) has
recently been detected in vineyards in southern Brazil. The ant Linepithema
micans (Forel) (Hymenoptera: Formicidae) is the most abundant and frequent
species in these vineyards, acting mainly as a disperser of the native soil
scale, the ground pearl Eurhizococcus brasiliensis (Wille) (Hemiptera:
Margarodidae). This study evaluated the interactions (dispersal and predation) of
L. micans with P. ficus. The first experiment evaluated the interaction between
L. micans and P. ficus in a greenhouse, using Paulsen 1103 rootstock (Vitis
berlandieri * Vitis rupestris) planted in pots. Plants were infested by 1) adult
females of P. ficus, and 2) adult females of P. ficus and L. micans, and all
mealybugs remaining after the experimental period were counted. To evaluate P.
ficus predation by L. micans, two laboratory experiments were conducted (25
degrees C, 80% relative humidity). In the first experiment, sprouted potatoes
were infested with ovisacs, first-instar nymphs and adult females of P. ficus and
evaluated in three treatments: 1) L. micans fed with carbohydrate and protein, 2)
L. micans without food, and 3) without ants present. In the second, potatoes were
infested only with first-instar nymphs of P. ficus and were exposed in two
treatments: 1) L. micans without food, and 2) without ants present. The results
were evaluated by counting the remaining mealybugs, with and without ants. The
results showed that L. micans does not transport P. ficus, and predates on first
instar nymphs of the mealybug.
PMID- 29939241
TI - Delayed cardiac tamponade after catheter ablation therapy due to a Valsalva
manoeuvre.
AB - A 23-year-old man, diagnosed with Wolff-Parkinson-White syndrome and who had
undergone several catheter ablations, presented 2 months after the most recent
ablation with cardiac tamponade following physical exertion. Emergency surgery
revealed a perforation between the inferior vena cava and the right atrium. This
perforation was repaired with a bovine pericardium patch. To our knowledge, this
is the first case of delayed cardiac tamponade after catheter ablation due to a
Valsalva manoeuvre (such as weightlifting) in a patient with a normal
international normalized ratio and normal platelet count.
PMID- 29939242
TI - The effect of a multidisciplinary intervention program for overweight and obese
children on cardiorespiratory fitness and blood pressure.
AB - Background: Multidisciplinary intervention programs for overweight and obese
children mainly focus on reducing bodyweight and body mass index (BMI), but they
may also positively impact blood pressure (BP), and cardiorespiratory fitness
(CRF), which is a stronger predictor for all-cause mortality than BMI. Objective:
To evaluate whether Kids4Fit, a multidisciplinary weight reduction program, has a
positive effect on CRF and BP in overweight and obese children in socially
deprived areas. Methods: A quasi-experimental study design with a waiting list
control period including children who participated in a multidisciplinary
intervention program of 12 weeks was set-up. Blood pressure measurements and
shuttle-run test (SRT) were performed at baseline, at the start of the
intervention, at the end of intervention and after 52 weeks. The effect of
Kids4Fit on BP and on SRT scores were analyzed using mixed models. Results: A
total of 154 children were included [mean age 8.5 years (SD 1.8)]. No significant
change was seen in systolic BP percentiles at 52 weeks after start of the
Kids4Fit intervention (beta 0.08, (95%CI -0.06, 0.22)). Diastolic BP percentiles
increased significantly over time (beta 0.20 (0.08, 0.31)). Effect plots showed
an initial significant increase of the SRT scores but this effect diluted after
the intervention. Conclusion: A local multidisciplinary intervention program in
deprived areas had a significant positive effect on CRF, but this effect diluted
after the intervention. Diastolic BP percentiles significantly increased over
time. However, systolic BP did not change over time.
PMID- 29939243
TI - Pre-exposure intradermal rabies vaccination: a non-inferiority trial in healthy
adults on shortening the vaccination schedule from 28 to 7 days.
AB - Background: The existing four-week pre-exposure rabies vaccination schedule is
costly and often not practicable. Shorter effective schedules would result in
wider acceptance. Methods: We conducted a non-inferiority trial in 500 healthy
adults comparing the safety and immunogenicity of a two-visit (day 0 and day 7)
intradermal (ID) primary vaccination (two doses of 0.1 ml ID of the human diploid
cell culture rabies vaccine (HDCV) at day 0 and 7) versus a standard three-visit
schedule (single dose of 0.1 mL ID at day 0, 7, and 28). One to three years after
primary vaccination, a single booster dose of 0.1 mL ID of HDCV was given to
evaluate the anamnestic rabies antibody response. The primary endpoint for
immunogenicity was the percentage of subjects with an adequate antibody level
>0.5 IU/mL seven days after the booster injection. The safety endpoint was the
proportion of participants developing adverse reactions following the primary
vaccination and/or booster dose. Results: All subjects in both study groups
possessed a rabies antibody titer >0.5 IU/mL on day 7 following the booster dose.
Following the booster dose, subjects exposed to the double-dose two-visit ID
schedule had a geometric mean titer of 37 IU/ml versus 25 IU/ml for the single
dose three-visit schedule (p<0.001). Local reactions at the injection site
following primary vaccination were mild and transient. Conclusion: In healthy
adults, ID administration of a double dose of 0.1 ml of HDCV over two-visits (day
0 and day 7) was safe and not inferior to the single-dose three-visit schedule.
PMID- 29939244
TI - PtRFdb: a database for plant transfer RNA-derived fragments.
AB - Transfer RNA-derived fragments (tRFs) represent a novel class of small RNAs
(sRNAs) generated through endonucleolytic cleavage of both mature and precursor
transfer RNAs (tRNAs). These 14-28 nt length tRFs that have been extensively
studied in animal kingdom are to be explored in plants. In this study, we
introduce a database of plant tRFs named PtRFdb (www.nipgr.res.in/PtRFdb), for
the scientific community. We analyzed a total of 1344 sRNA sequencing datasets of
10 different plant species and identified a total of 5607 unique tRFs (758 tRF-1,
2269 tRF-3 and 2580 tRF-5), represented by 487 765 entries. In PtRFdb, detailed
and comprehensive information is available for each tRF entry. Apart from the
core information consisting of the tRF type, anticodon, source organism, tissue,
sequence and the genomic location; additional information like PubMed identifier
(PMID), Sample accession number (GSM), sequence length and frequency relevant to
the tRFs may be of high utility to the user. Two different types of search
modules (Basic Search and Advanced Search), sequence similarity search (by BLAST)
and Browse option with data download facility for each search is provided in this
database. We believe that PtRFdb is a unique database of its kind and it will be
beneficial in the validation and further characterization of plant tRFs.Database
URL: http://www.nipgr.res.in/PtRFdb/.
PMID- 29939245
TI - Mineralocorticoid receptor antagonists for heart failure: lost in translation?
PMID- 29939246
TI - Variation in preoperative antithrombotic strategy, severe bleeding, and use of
blood products in coronary artery bypass grafting: results from the multicentre E
CABG registry.
AB - Aims: No data exists on inter-institutional differences in terms of adherence to
international guidelines regarding the discontinuation of antithrombotics and
rates of severe bleeding in coronary artery bypass grafting (CABG). Methods and
results: This is an analysis of 7118 patients from the prospective multicentre
European CABG (E-CABG) registry who underwent isolated CABG in 15 European
centres. Preoperative pause of P2Y12 receptor antagonists shorter than that
suggested by the 2017 ESC guidelines (overall 11.6%) ranged from 0.7% to 24.8%
between centres (adjusted P < 0.0001) and increased the rate of severe-massive
bleeding [E-CABG bleeding grades 2-3, OR 1.66, 95% confidence interval (CI) 1.27
2.17; Universal Definition of Perioperative Bleeding (UDPB) bleeding grades 3-4,
OR 1.50, 95% CI 1.16-1.93]. The incidence of resternotomy for bleeding (overall
2.6%) ranged from 0% to 6.9% (adjusted P < 0.0001), and surgical site bleeding
(overall 59.6%) ranged from 0% to 84.6% (adjusted P = 0.003). The rate of the
UDPB bleeding grades 3-4 (overall 8.4%) ranged from 3.7% to 22.3% (P < 0.0001),
and of the E-CABG bleeding grades 2-3 (overall 6.5%) ranged from 0.4% to 16.4%
between centres (P < 0.0001). Resternotomy for bleeding (adjusted OR 5.04, 95% CI
2.85-8.92), UDPB bleeding grades 3-4 (adjusted OR 6.61, 95% CI 4.42-9.88), and E
CABG bleeding grades 2-3 (adjusted OR 8.71, 95% CI 5.76-13.15) were associated
with an increased risk of hospital/30-day mortality. Conclusions: Adherence to
the current guidelines on the early discontinuation of P2Y12 receptor antagonists
is of utmost importance to reduce excessive bleeding and early mortality after
CABG. Inter-institutional variation should be considered for a correct
interpretation of the results in multicentre studies evaluating perioperative
bleeding and use of blood products.
PMID- 29939247
TI - Bacterial and fungal communities in boreal forest soil are insensitive to changes
in snow cover conditions.
AB - The northern regions are experiencing considerable changes in winter climate
leading to more frequent warm periods, rain-on-snow events and reduced snow pack
diminishing the insulation properties of snow cover and increasing soil frost and
freeze-thaw cycles. In this study, we investigated how the lack of snow cover,
formation of ice encasement and snow compaction affect the size, structure and
activities of soil bacterial and fungal communities. Contrary to our hypotheses,
snow manipulation treatments over one winter had limited influence on microbial
community structure, bacterial or fungal copy numbers or enzyme activities.
However, microbial community structure and activities shifted seasonally among
soils sampled before snow melt, in early and late growing season and seemed
driven by substrate availability. Bacterial and fungal communities were dominated
by stress-resistant taxa such as the orders Acidobacteriales, Chaetothyriales and
Helotiales that are likely adapted to adverse winter conditions. This study
indicated that microbial communities in acidic northern boreal forest soil may be
insensitive to direct effects of changing snow cover. However, in long term, the
detrimental effects of increased ice and frost to plant roots may alter plant
derived carbon and nutrient pools to the soil likely leading to stronger
microbial responses.
PMID- 29939248
TI - Science in the Public Eye: Leveraging Partnerships-An Introduction.
AB - With stories of struggle and dramatic breakthroughs, science has incredible
potential to interest the public. However, as the rhetoric of outrage surrounds
controversies over science policy there is an urgent need for credible, trusted
voices that frame science issues in a way that resonates with a diverse public. A
network of informal educators, park rangers, museum docents and designers, and
zoo and aquarium interpreters are prepared to do so during millions of visits a
year; just where science stories are most meaningfully told-in the places where
members of the public are open to learning. Scientific researchers can benefit
from partnerships with these intermediaries who are accorded status for their
trustworthiness and good will, who have expertise in translating the science
using language, metaphors, encounters, and experiences that are appropriate for
non-experts. In this volume, we describe and probe examples wherein scientists
work productively with informal educators and designers, artists, staff of
federal agencies, citizen scientists, and volunteers who bring science into the
public eye.
PMID- 29939249
TI - The Comparative Biology of Mitochondrial Function and the Rate of Aging.
AB - The mitochondrial hypothesis of aging evolved from the rate-of-living theory.
That theory posited that the rate of aging was largely determined by the rate of
energy expenditure. The mechanistic link between energy expenditure and aging was
hypothesized to be oxidative stress. As both energy expenditure and reactive
oxygen species (ROS) centered on the mitochondria that organelle became a central
focus of aging research. Until about the turn of the 21st century available
evidence largely supported the efficiency of mitochondrial function as a key
contributor to aging. However as methods for investigating mitochondrial oxidant
production and tissue level oxidative damage improved, evidentiary support for
the theory weakened. Recently, direct disruption of mitochondrial function has
been shown not to shorten life or health as expected, but in many cases in
multiple laboratory species disrupted mitochondrial function has lengthened life,
sometimes without apparent tradeoffs. Does this mean that mitochondrial function
plays no role in aging as had been posited for many years? One key consideration
is that experiments under laboratory conditions can be misleading about
physiological processes that occur in the uncertain conditions of nature. Before
we discard the mitochondrial hypothesis of aging, more field experiments targeted
at that hypothesis need to be performed. Fortunately, emerging technology is
making such experiment more possible than ever before.
PMID- 29939250
TI - A disintegrin and metalloproteinase 15-mediated glycocalyx shedding contributes
to vascular leakage during inflammation.
AB - Aims: Endothelial hyperpermeability exacerbates multiple organ damage during
inflammation or infection. The endothelial glycocalyx, a protective matrix
covering the luminal surface of endothelial cells (ECs), undergoes enzymatic
shedding during inflammation, contributing to barrier hyperpermeability. A
disintegrin and metalloproteinase 15 (ADAM15) is a sheddase capable of cleaving
the ectodomains of membrane-bound molecules. Herein, we tested whether and how
ADAM15 is involved in glycocalyx shedding and vascular leakage during sepsis.
Methods and results: Dextran-150kD exclusion assay revealed lipopolysaccharide
(LPS) significantly reduced glycocalyx thickness in mouse cremaster microvessels.
Consistently, shedding products of glycocalyx constituents, including CD44
ectodomain, were detected with an increased plasma level after cecal ligation and
puncture (CLP)-induced sepsis. The direct effects of CD44 ectodomain on
endothelial barrier function were evaluated, which revealed CD44 ectodomain dose
dependently reduced transendothelial electrical resistance (TER) and caused cell
cell adherens junction disorganization. Furthermore, we examined the role of
ADAM15 in CD44 cleavage and glycocalyx shedding. An in vitro cleavage assay
coupled with liquid chromatography-tandem mass spectrometry confirmed ADAM15
cleaved CD44 at His235-Thr236 bond. In ECs with ADAM15 knockdown, LPS-induced
CD44 cleavage and TER reduction were greatly attenuated, whereas, ADAM15
overexpression exacerbated CD44 cleavage and TER response to LPS. Consistently,
ADAM15 knockout in mice attenuated CLP-induced increase in plasma CD44.
Intravital and electron microscopic images revealed ADAM15 deficiency prevented
LPS-induced glycocalyx injury in cremaster and pulmonary microvasculatures.
Functionally, ADAM15-/- mice with better-preserved glycocalyx exhibited
resistance to LPS-induced vascular leakage, as evidenced by reduced albumin
extravasation in pulmonary and mesenteric vessels. Importantly, in intact,
functionally vital human lungs, perfusion of LPS induced a significant up
regulation of ADAM15, accompanied by elevated CD44 in the effluent and increased
vascular permeability to albumin. Conclusion: Together, our data support the
critical role of ADAM15 in mediating vascular barrier dysfunction during
inflammation. Its mechanisms of action involve CD44 shedding and endothelial
glycocalyx injury.
PMID- 29939251
TI - Metabolic Scaling of Stress Hormones in Vertebrates.
AB - Glucocorticoids (GCs) are stress hormones that can strongly influence physiology,
behavior, and an organism's ability to cope with environmental change. Despite
their importance, and the wealth of studies that have sought to understand how
and why GC concentrations vary within species, we do not have a clear
understanding of how circulating GC levels vary within and across the major
vertebrate clades. New research has proposed that much interspecific variation in
GC concentrations can be explained by variation in metabolism and body mass.
Specifically, GC concentrations should vary proportionally with mass-specific
metabolic rates and, given known scaling relationships between body mass and
metabolic rate, GC concentrations should scale to the -1/4 power of body mass and
to the power of 1 with mass-specific metabolic rate. Here, we use HormoneBase,
the newly compiled database that includes plasma GC concentrations from free
living and unmanipulated vertebrates, to evaluate this hypothesis. Specifically,
we explored the relationships between body mass or mass-specific metabolic rate
and either baseline or stress-induced GC (cortisol or corticosterone)
concentrations in tetrapods. Our phylogenetically-informed models suggest that,
whereas the relationship between GC concentrations and body mass across tetrapods
and among mammals is close to -1/4 power, this relationship does not exist in
amphibians, reptiles, and birds. Moreover, with the exception of a positive
association between stress-induced GC concentrations and mass-specific metabolic
rate in birds, we found little evidence that GC concentrations are linked to
metabolic rate, although the number of species sampled was quite limited for
amphibians and somewhat so for reptiles and mammals. Nevertheless, these results
stand in contrast to the generally accepted association between the two and
suggest that our observed positive association between body mass and GC
concentrations may not be due to the well-established link between mass and
metabolism. Large-scale comparative approaches can come with drawbacks, such as
pooling and pairing observations from separate sources. However, these broad
analyses provide an important counterbalance to the majority of studies examining
variation in GC concentrations at the population or species level, and can be a
powerful approach to testing both long-standing and new questions in biology.
PMID- 29939252
TI - Pouchitis as an Indication for Ileal Pouch Surgical Revision.
PMID- 29939253
TI - Experience with fully covered self-expandable metal stents for anastomotic
stricture following esophageal atresia repair.
AB - There is a lack of experience with fully covered self-expandable metal stents
(SEMSs) for the treatment of benign esophageal conditions in the pediatric
population. This is the evaluation of our institutional experience of placing
SEMSs for anastomotic stricture (AS) formation following esophageal atresia (EA)
repair. Patients were jointly managed from the Department of Pediatric Surgery
and Central Interdisciplinary Endoscopy at our institution. Thirteen children (8
male, 5 female) with a median age of 4 months (range: 1-32 months) who underwent
treatment with SEMSs for a postoperative AS following EA repair between February
2006 and April 2016 were recruited into this retrospective study. SEMSs that are
originally designed for other organs such as trachea, bronchus, biliary tract, or
colon were inserted under general anesthesia via endoscopic guidance.
Simultaneous fluoroscopy was not required in any case. In five infants, the
stents were inserted primarily without previous therapy. Seven patients underwent
stenting following dilatation with or without adjuncts (e.g. Mitomycin C,
Triamcinolone). In one case with an AS and a simultaneous persistent
tracheoesophageal fistula (TEF), multiple SEMSs were applied after failure to
close the fistula with fibrin glue.The median duration of individual stent
placement was 30 days (range: 5-91 days). In five children up to four different
biliary, bronchial or colonic SEMSs were placed successively over time. There
were no problems noted at stent insertion or removal. Eight children (62%)
developed complications associated with stenting. At follow-up, in eight patients
(62%) AS was resolved, including all of those five cases, who had their stents
inserted without previous therapy. Five children (38%), who underwent dilatation
prior to stenting did not improve their AS and required further intervention.
Overall, the cohort exhibited a slight, but not significant weight gain between
stent insertion and (final) stent removal.Insertion of SEMSs for AS following EA
repair is safe and often successful with only one single application. It can be
used as a primary procedure (without previous therapy) or after failed
dilatations.There was one death in this study that was unrelated to stenting and
occurred 12 months after stent removal. Because of the absence of manufactured,
age-related devices, SEMSs that are originally designed for other organs can be
applied. Establishment of a standardized management including stent placement for
the treatment of AS following EA repair in the pediatric population is required.
PMID- 29939255
TI - Surgical repair of huge ascending aortic and arch aneurysms with aortic
dissection combined with pulmonary artery dissection and aortopulmonary artery
fistula.
AB - An aortopulmonary artery fistula combined with aortic and pulmonary artery
dissection is extremely rare, and very few cases have been reported to date.
Herein, we present a 38-year-old man with huge ascending aortic, arch and thoraco
abdominal aneurysms with chronic aortic dissection, pulmonary artery dissection
and aortopulmonary fistula. Surgery was performed to replace the ascending aorta
and the entire arch combined with a conventional elephant trunk implantation to
correct the pulmonary artery dissection and repair the aortopulmonary fistula
under selective cerebral perfusion with deep hypothermic circulatory arrest. The
patient recovered uneventfully. A second-stage operation will be needed to
replace the thoraco-abdominal aorta.
PMID- 29939254
TI - Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with
Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE
2.
AB - Background and Aims: Adalimumab has been shown to be more effective than placebo
in healing fistulae in adults with moderately to severely active Crohn's disease.
The efficacy and safety of adalimumab in healing fistulae in children/adolescents
with Crohn's disease from the 52-week IMAgINE 1 clinical trial, and its open
label extension IMAgINE 2, are reported. Methods: Children/adolescents with
perianal fistulae at baseline of IMAgINE 1 were assessed for fistula closure and
improvement during IMAgINE 1 [Weeks 0-52] and from Week 0 of IMAgINE 2 [Week 52
of IMAgINE 1] through to Week 240 of IMAgINE 2 using non-responder imputation.
Results: A total of 36 children/adolescents had fistulae at baseline of IMAgINE 1
and were included in the analysis. Fistula closure and improvement were observed
in 44.4% and 52.8%, respectively, at Week 12. Rates of closure and improvement
were maintained throughout the analysis period to Week 292. No new safety signals
were identified. Conclusions: In children/adolescents with moderately to severely
active, fistulizing Crohn's disease, adalimumab induced perianal fistula closure
and improvement within 12 weeks of treatment, with rates that were sustained for
more than 5 years. The safety profile of adalimumab in patients with fistulae at
baseline was similar to that of the overall population in IMAgINE 1/2.
ClinicalTrials.gov identifiers: IMAgINE 1 (NCT00409682); IMAgINE 2 (NCT00686374).
PMID- 29939256
TI - Subcutaneous implantable cardioverter-defibrillator: is it ready for use in
children and young adults? A single-centre study.
AB - Aims: Use of the subcutaneous implantable cardioverter-defibrillator (S-ICD) to
prevent sudden cardiac death is increasing. Few data exist on S-ICD in young
patients. We reviewed our single-centre experience in order to assess the
effectiveness and safety of S-ICD implantation, and to identify potential factors
associated with complications. Methods and results: Observational, non
randomized, standard-of-care study on S-ICD implantation/follow-up in young
patients with inherited arrhythmias (IA), cardiomyopathies, and congenital heart
defects (CHD). Fifteen patients (6 CHD, 8 cardiomyopathies, and 1 IA), median age
15 years (25th-75th centiles, 14-28), 10 of them <18 years, with body mass index
(BMI) 22.6 +/- 3.4, underwent S-ICD implantation (primary prevention 93%). The
first six patients underwent a standard implantation procedure (three surgical
incisions), the following nine a two-incision procedure. No intraoperative
complications occurred. Over 12 (7-24) months follow-up, two patients received
appropriate shocks and one (7%) inappropriate shock. Four patients had device
related complications requiring surgical intervention: three skin erosions at the
superior parasternal incision, one pocket infection. A higher risk of
complications was seen in patients who underwent standard procedures [hazard
ratio (HR) 4.98, 95% confidence interval (CI) 1.53-47.36; P = 0.0482] and those
with BMI <20 (HR 9.44, 95% CI 0.95-93.23; P = 0.0169). Conclusion: S-ICD
implantation was safe and effective in young patients with low rates of
inappropriate shock. However, the risk of device-related complications during
follow-up remains substantial in patients with low BMI. To prevent possible
complications, a two-incision technique should be preferred.
PMID- 29939257
TI - Clutch cutter is a safe device for performing endoscopic submucosal dissection of
superficial esophageal neoplasms: a western experience.
AB - Although the endoscopic submucosal dissection (ESD) has been established to be
more efficacious in the treatment of superficial gastrointestinal neoplasia than
the piecemeal resection, its use is still limited due to the concern about
serious adverse events particularly in the west. Newer ESD knives have been
developed that have been said to be safer than the first-generation devices. We
aimed to report a Western single center experience regarding the initial safety
and performance of ESD for superficial esophageal neoplasia treated with the
Clutch Cutter (DP2618DT; Fujifilm Corporation, Tokyo, Japan). Our main outcome
was safety in terms of bleeding or perforation. Secondary outcomes included en
bloc resection and the R0 resection. Fourteen patients with superficial
esophageal neoplasia underwent 15 ESDs using the Clutch Cutter. The mean age was
65 +/- 16.7 years and 10 (71.4%) males. Eight (57%) patients had esophageal
adenocarcinoma, 3 (21.4%) had high-grade dysplasia, 1 (7%) had nodular low-grade
dysplasia, and 2 (14.3%) had squamous cell carcinoma. Mild anticipated
intraprocedural bleeding was present with most procedures. However, no
significant postoperative bleeding or perforation was encountered. One patient
had mild chest pain postprocedure. En bloc resection was achieved in all lesions
100%. Histological R0 was achieved in 5/12 lesions (41.6%). The mean length of
the resected area was 24.8 +/- 13 mm (IQR: 17-30 mm). All patients were safely
discharged home after overnight observation. In conclusion, this is the largest
series of esophageal ESD using the multimodal Clutch Cutter in the United States;
we found that the device effectively achieved en bloc resection of superficial
esophageal neoplasia without significant adverse events. The use of the Clutch
Cutter should be considered as one option to minimize adverse events during ESD
in the Western population.
PMID- 29939258
TI - A rare cardiovascular malformation of a multilobulated arch aneurysm with
localized aortic dissection.
PMID- 29939259
TI - Epidemiologic Investigation of Chemical Burns in Southwestern China from 2005 to
2016.
AB - The epidemiological characteristics of chemical burns vary in different regions
of the world. This study aims to survey the epidemiology, outcomes, and costs of
chemical burns in southwest China, to determine associated risk factors and to
obtain data for developing an effective approach to prevent and treat chemical
burns. This retrospective study includes 410 cases with chemical burns admitted
to the Institute of Burn Research of Southwest Hospital from 2005 to 2016. Data,
including demographic, etiology, outcomes, and costs, were collected and
analyzed. A total of 410 cases admitted to our burn center were included. The
average age of the burn patients was 38.58 +/- 14.66 years. The incidence of
chemical burns peaked in autumn. The most common etiology were acids. Limbs were
the most common burn sites (59.51%). Average total body surface area (TBSA) was
12.37 +/- 18.67%. The percentage of patients who underwent procedures and the
number of procedures were significantly greater for TBSA and full-thickness
burns. The mortality of chemical burns was 1.22%. The median length of stay (LOS)
and cost were 21 days and 65,852 CNY, respectively. The major risk factors for
cost were the number of procedures, TBSA and full-thickness burns, the major risk
factors for LOS were the number of procedures and outcome. Chemical burns mainly
occurred in adult males with occupational exposures to chemical agents due to
inappropriate operation. Emphasis on safety education for the public and
professional pre-employment training for workers should become key preventive
targets to reduce the incidence of chemical burns.
PMID- 29939260
TI - Cohort Profile: Ifanadiana Health Outcomes and Prosperity longitudinal Evaluation
(IHOPE).
PMID- 29939261
TI - The effect of lactic acid bacteria inoculation, molasses or wilting on the
fermentation quality and nutritive value of amaranth (Amaranthus hypochondriaus)
silage.
AB - This study assessed the influence of wilting, lactobacillus (LAB) and / or
molasses on the chemical composition, phenolic compounds, in situ degradability
and in vitro ruminal fermentation parameters of amaranth (var. Maria) silage
using a randomized complete block design with 6 replicates. Treatments were fresh
amaranth forage (FAF), ensiled amaranth without additive (EA), EA inoculated with
LAB (EAB), EA + 5% of molasses (EAM), EA inoculated with LAB + 5% of molasses
(EABM) and 24-h wilted EA (WEA). The ensiled materials were stored anaerobically
for a period of 45 d. Chemical composition, oxalic acid and nitrate levels,
silage fermentation characteristics, DM disappearance (DMD), OM disappearance
(OMD), in vitro ruminal ammonia-N, VFA, cellulolytic bacteria and protozoa
counts, and in situ DM and CP degradability were determined. Compared with FAF,
EA had a lesser values of water-soluble carbohydrates (P = 0.023), nitrate (P =
0.001), total phenolics (P = 0.04), total tannins (P = 0.01), DMD (P = 0.01),
ruminal cellulolytic bacteria (P = 0.02), soluble and very rapidly degradable
fraction (P = 0.014), and effective degradability (P = 0.01). The EA had lesser
OMD and CP degradability compared with FAF (P < 0.05). Adding molasses to EA
resulted in increased ash and lactate concentrations and decreased ammonia (P <
0.05), but had no effect on OMD. The WEA had lesser ammonia and greater lactate
compared to EA (P < 0.05). Overall, fresh amaranth var. Maria can be preserved as
a valuable silage to feed ruminants. Ensiling amaranth var. Maria decreased the
anti-quality compounds, and molasses addition improved the fermentation quality
of the silage.
PMID- 29939262
TI - Dim light at night: physiological effects and ecological consequences for
infectious disease.
AB - Light pollution has emerged as a pervasive component of land development over the
past century. Several detrimental impacts of this anthropogenic influence have
been identified in night shift workers, laboratory rodents, and a plethora of
wildlife species. Circadian, or daily, patterns are interrupted by the presence
of light at night and have the capacity to alter rhythmic physiological or
behavioral characteristics. Indeed, biorhythm disruption can lead to metabolic,
reproductive, and immunological dysfunction depending on the intensity, timing,
duration, and wavelength of light exposure. Light pollution, in many forms and by
many pathways, is thus apt to affect the nature of host-pathogen interactions.
However, no research has yet investigated this possibility. The goal of this
manuscript is to outline how dim light at night, a relevant and common form of
light pollution, may affect disease dynamics by interrupting circadian rhythms
and regulation of immune responses as well as opportunities for host-parasite
interactions and subsequent transmission risk including spillover into humans. We
close by proposing some promising interventions including alternative lighting
methods or vector control efforts.
PMID- 29939263
TI - Pregnancy complications following fertility treatment-disentangling the role of
multiple gestation.
AB - Background: To assess the extent to which multiple gestations mediate risk of
pregnancy complications from fertility treatment and to address possible
confounding by the underlying infertility. Methods: From the nearly 1.8 million
pregnancies recorded in the Swedish Medical Birth Register between 1996 and 2013,
we selected the 9.9% (N = 174 067) that occurred to couples with known trouble
conceiving (clinical infertility). Fertility treatment was identified from self
reports, medical records and procedural information from fertility clinics. We
used logistic regression to estimate odds ratios (ORs) and their 95% confidence
intervals (CIs), and decomposed the total effect into direct and mediated effects
to estimate the proportion mediated by multiple gestations. Results: Compared
with pregnancies achieved without any assistance, those having received some
treatment had higher odds of all studied complications except gestational
diabetes. Associations with placenta previa (OR 2.17, 95% CI 1.95-2.40) and
placental abruption (OR 1.77, 95% CI 1.54-2.03) were almost entirely independent
of multiple gestations. In contrast, the majority of the associations with
preterm birth (OR 1.69, 95% CI 1.62-1.77), caesarean delivery (RR 1.15, 95% CI
1.13-1.17) and pre-eclampsia (OR 1.17, 95% CI 1.11-1.22) were mediated by
multiple gestations (87%, 62% and 91% of the effect mediated, respectively). Both
direct and mediated pathways contributed to the remaining positive associations
with chorioamnionitis, labour induction and postpartum haemorrhage. Results were
similar when considering primi- and multi-parous women separately, and after
restriction to assisted reproductive technologies only. Conclusion: Multiple
gestations are responsible for a large proportion of pregnancy complications
associated with fertility treatment, suggesting that interventions to restrict
the occurrence of multiples could reduce excess risk of pre-eclampsia, preterm
birth and caesarean delivery after fertility treatment. However, the elevated
risk of serious placental complications after fertility treatment appears to be
largely independent of multiple gestations.
PMID- 29939265
TI - Commentary: The impact of military service on the children of veterans: A problem
not to be ignored despite the uncertainties.
PMID- 29939264
TI - Suicidal Ideation and Suicidal Behavior as Rare Adverse Events of Antidepressant
Medication: Current Report from the AMSP Multicenter Drug Safety Surveillance
Project.
AB - Background: Suicidal ideations, suicide attempts, and fatal suicides are rare
adverse drug reactions to antidepressant drugs, but they essentially are
clinically relevant. Drawing on a larger dataset of the European drug
surveillance program, the present naturalistic study updates a previous
contribution (Stubner et al., 2010). Methods: First an analysis of the
comprehensive data collected in 81 psychiatric hospitals from 1993 to 2014 by the
European drug surveillance program Arzneimittelsicherheit in der Psychiatrie was
made. All documented single cases of suicidal ideations or behavior judged as
adverse drug reactions to antidepressant drugs were carefully assessed as to
their clinical features and drug prescriptions. Results: Among 219,635 adult
hospitalized patients taking antidepressant drugs under surveillance, 83 cases of
suicidal adverse drug reactions occurred (0.04%): 44 cases of suicidal ideation,
34 attempted suicides, and 5 committed suicides were documented. Restlessness was
present in 42 patients, ego-dystonic intrusive suicidal thoughts or urges in 39
patients, impulsiveness in 22 patients, and psychosis in 7 patients. Almost all
adverse drug reactions occurred shortly after beginning antidepressant drug
medication or increasing the dosage. Selective serotonin reuptake inhibitors
caused a higher incidence of suicidal ideation and suicidal behavior as adverse
drug reactions than noradrenergic and specific serotonergic antidepressants or
tricyclic antidepressants, as did monotherapy consisting of one antidepressant
drug, compared to combination treatments. Conclusions: The study supports the
view that antidepressant drug-triggered suicidal ideation and suicidal behavior
(primarily with selective serotonin reuptake inhibitors) are rare. Special
clinical features (restlessness, ego-dystonic thoughts or urges, impulsiveness)
may be considered as possible warning signs. A combination therapy might be
preferable to antidepressant drug monotherapy when beginning treatment.
PMID- 29939266
TI - Kelch-like protein 14 promotes B-1a but suppresses B-1b cell development.
AB - B-1 cells are innate-like B-cell population and produce natural antibodies that
contribute to the first line of host defense. There are two subsets of B-1 cells:
B-1a and B-1b. B-1a cells are the main producer of poly-reactive and autoreactive
natural IgM antibodies, whereas B-1b cells can respond specifically to T-cell
independent antigens. Despite the functional significance of B-1a and B-1b cells,
little information is available about what regulates the development of these two
subsets. We found that Kelch-like protein 14 (KLHL14) was expressed at high
levels in B cells but only at low levels in a few non-lymphoid tissues. Although
mice lacking KLHL14 died right after birth, the heterozygotes developed normally
with no gross abnormalities by appearance. B-cell development in the bone marrow
and maturation and activation in the spleen were not affected in the heterozygous
mice. However, the number of peritoneal B-1a cells was significantly reduced
while B-1b cells were increased in Klhl14 heterozygous mice compared with wild
type (WT) mice. Consistently, Rag1-/- mice reconstituted with Klhl14-/- fetal
liver cells had a more severe reduction of B-1a and an increase of B-1b cells in
the peritoneal cavity. KLHL14 did not affect the turnover or apoptosis of B-1a
and B-1b cells in vivo. Moreover, Klhl14-/- fetal liver contained a similar
proportion and absolute numbers of the B-1 progenitor cells as did WT fetal
liver. These results suggest that KLHL14 promotes B-1a development in mice.
PMID- 29939267
TI - Ceftazidime/avibactam versus standard-of-care agents against carbapenem-resistant
Enterobacteriaceae harbouring blaKPC in a one-compartment
pharmacokinetic/pharmacodynamic model.
AB - Background: 'Last-line' antimicrobial usage has promoted the emergence of MDR
bacteria. Production of Klebsiella pneumoniae carbapenemases (KPCs) is
increasingly common and leads to resistance to most antimicrobials. However,
ceftazidime/avibactam demonstrates activity against KPC-producing strains.
Ceftazidime/avibactam in the empirical setting remains unknown. Methods: Strains
underwent genetic analysis evaluating blaKPC presence/production and MICs were
determined. Four strains were assessed in an in vitro, one-compartment
pharmacokinetic (PK)/pharmacodynamic (PD) model for 96 h. The following bolus
dosing exposures were tested: 2.5 g of ceftazidime/avibactam every 8 h, 2 g of
meropenem every 8 h, 1.25 mg/kg polymyxin B every 12 h, amikacin 'once-daily
dosing' (peak of 70-80 mg/L), tigecycline at 200 mg *1 dose followed by 100 mg
every 12 h, and a drug-free growth control. Results: Thirty blaKPC-producing
strains were evaluated; 97% of strains were ceftazidime/avibactam susceptible
with MIC50/MIC90 values of 0.38/1.5 mg/L (range 0.032-16 mg/L). Two K. pneumoniae
strains, one Klebsiella oxytoca strain and one Citrobacter freundii strain
underwent further analysis in PK/PD models. Ceftazidime/avibactam displayed
potent activity with a reduction of 4.23 +/- 0.42 cfu/mL from the initial
inoculum at 96 h. Against susceptible isolates, amikacin displayed similar
activity compared with ceftazidime/avibactam at 96 h, although this was not
demonstrated against all strains. Polymyxin B produced comparable activity to
ceftazidime/avibactam against two strains. Neither meropenem nor tigecycline
produced effective killing and were comparable to the drug-free growth control at
96 h. Conclusions: blaKPC-producing organisms demonstrated susceptibility to
ceftazidime/avibactam and bactericidal activity was observed in the PK/PD model.
Based on these data, ceftazidime/avibactam is a valuable agent for treating KPC
producing organisms and should be considered for treatment of infections caused
by these pathogens.
PMID- 29939268
TI - Evaluating large-scale propensity score performance through real-world and
synthetic data experiments.
AB - Background: Propensity score adjustment is a popular approach for confounding
control in observational studies. Reliable frameworks are needed to determine
relative propensity score performance in large-scale studies, and to establish
optimal propensity score model selection methods. Methods: We detail a propensity
score evaluation framework that includes synthetic and real-world data
experiments. Our synthetic experimental design extends the 'plasmode' framework
and simulates survival data under known effect sizes, and our real-world
experiments use a set of negative control outcomes with presumed null effect
sizes. In reproductions of two published cohort studies, we compare two
propensity score estimation methods that contrast in their model selection
approach: L1-regularized regression that conducts a penalized likelihood
regression, and the 'high-dimensional propensity score' (hdPS) that employs a
univariate covariate screen. We evaluate methods on a range of outcome-dependent
and outcome-independent metrics. Results: L1-regularization propensity score
methods achieve superior model fit, covariate balance and negative control bias
reduction compared with the hdPS. Simulation results are mixed and fluctuate with
simulation parameters, revealing a limitation of simulation under the
proportional hazards framework. Including regularization with the hdPS reduces
commonly reported non-convergence issues but has little effect on propensity
score performance. Conclusions: L1-regularization incorporates all covariates
simultaneously into the propensity score model and offers propensity score
performance superior to the hdPS marginal screen.
PMID- 29939269
TI - Effect of a Hydrolyzed Mannan and Glucan Rich Yeast Fraction on Performance and
Health Status of Newly received Feedlot Cattle.
AB - A two-part experiment was conducted to determine the effects of a blend of
specialized mannan rich and glucan rich fractions of yeast (Select-TC, Alltech
Inc.) on the health status and performance of steers during the first two months
of the feedlot period. Eighty crossbred steers were acquired from commercial sale
barns in Mississippi and Georgia, and transported to Purdue University. All
animals were fed a corn silage based receiving diet, and were checked and treated
daily for respiratory disease as needed following established treatment
protocols. In Exp. 1, 64 steers (246.5 +/- 4.7 kg initial weight) were blocked by
body weight (BW) and randomly allocated to 2 treatments to determine the impact
of supplementation of a hydrolyzed mannan and glucan rich yeast fraction for 56 d
on BW, average daily gain (ADG), daily dry matter intake (DMI), and gain:feed:
hydrolyzed yeast fed at 13 g (as-fed)/steer daily (TC) or non-supplemented
control (CON). Steers in Exp. 1 were housed in bedded pens with 2 animals/pen (n
= 16 pens [32 steers]/treatment). In Exp. 2, 16 steers (247.1 +/- 5.4 kg initial
BW) were similarly allotted to two treatments (CON and TC), individually penned,
and subjected to a lipopolysaccharide (LPS) endotoxin challenge on d 62 or 63
after the start of the study to determine the animal's response to an
inflammatory agent. Serum samples and rectal temperatures were taken every half
an hour from -2 to 8 h relative to LPS injection from steers in Exp. 2. Data were
analyzed as a complete randomized block design using the MIXED procedure of SAS.
Morbidity for both experiments did not differ (P >= 0.16). Weight, ADG, DMI and
gain:feed, did not differ among treatments (P >= 0.32) in Exp. 1. After the LPS
infusion in Exp. 2, rectal temperatures (P = 0.03) and serum non-esterified fatty
acid (NEFA) concentration (P = 0.04) were decreased in TC compared to CON steers.
Concentrations of blood urea nitrogen (P = 0.31), glucose (P = 0.70), insulin (P
= 0.57) and cortisol (P = 0.77) did not differ by treatment after LPS
administration. Serum interleukin-6 concentrations were decreased (P < 0.0001)
and interferon-gamma concentrations tended to be greater (P = 0.07) in TC
compared to CON steers after LPS infusion. Serum cytokine and metabolite results
indicate that Select TC improved health and metabolic status of LPS-challenged
cattle, but this did not result in quantifiable improvements in performance in
the conditions observed in this study.
PMID- 29939270
TI - Low birthweight and preterm birth: trends and inequalities in four population
based birth cohorts in Pelotas, Brazil, 1982-2015.
AB - Background: Despite positive changes in most maternal risk factors in Brazil,
previous studies did not show reductions in preterm birth and low birthweight. We
analysed trends and inequalities in these outcomes over a 33-year period in a
Brazilian city. Methods: Four population-based birth cohort studies were carried
out in the city of Pelotas in 1982, 1993, 2004 and 2015, with samples ranging
from 4231 to 5914 liveborn children. Low birthweight (LBW) was defined as <2500
g, and preterm birth as less than 37 weeks of gestation. Information was
collected on family income, maternal skin colour and other risk factors for low
birthweight. Multivariable linear regression was used to estimate the
contribution of risk factors to time trends in birthweight. Results: Preterm
births increased from 5.8% (1982) to 13.8% (2015), and LBW prevalence increased
from 9.0% to 10.1%, being higher for boys and for children born to mothers with
low income and brown or black skin colour. Mean birthweight remained stable,
around 3200 g, but increased from 3058 to 3146 g in the poorest quintile and
decreased from 3307 to 3227 g in the richest quintile. After adjustment for risk
factors for LBW, mean birthweight was estimated to have declined by 160 g over
1982-2015 (reductions of 103 g in the poorest and 213 g in the richest
quintiles). Conclusions: Data from four birth cohorts show that preterm births
increased markedly. Mean birthweights remained stable over a 33-year period.
Increased prevalence of preterm and early term births, associated with high
levels of obstetric interventions, has offset the expected improvements due to
reduction in risk factors for low birthweight.
PMID- 29939272
TI - STAT4 is required for the generation of Th1 and Th2, but not Th17 immune
responses during monophosphoryl lipid A adjuvant activity.
PMID- 29939271
TI - The national cost of adverse drug events resulting from inappropriate medication
related alert overrides in the United States.
AB - Objective: To estimate the national cost of ADEs resulting from inappropriate
medication-related alert overrides in the U.S. inpatient setting. Materials and
Methods: We used three different regression models (Basic, Model 1, Model 2) with
model inputs taken from the medical literature. A random sample of 40 990 adult
inpatients at the Brigham and Women's Hospital (BWH) in Boston with a total of 1
639 294 medication orders was taken. We extrapolated BWH medication orders using
2014 National Inpatient Sample (NIS) data. Results: Using three regression
models, we estimated that 29.7 million adult inpatient discharges in 2014
resulted in between 1.02 billion and 1.07 billion medication orders, which in
turn generated between 75.1 million and 78.8 million medication alerts,
respectively. Taking the basic model (78.8 million), we estimated that 5.5
million medication-related alerts might have been inappropriately overridden,
resulting in approximately 196 600 ADEs nationally. This was projected to cost
between $871 million and $1.8 billion for treating preventable ADEs. We also
estimated that clinicians and pharmacists would have jointly spent 175 000 hours
responding to 78.8 million alerts with an opportunity cost of $16.9 million.
Discussion and Conclusion: These data suggest that further optimization of
hospitals computerized provider order entry systems and their associated clinical
decision support is needed and would result in substantial savings. We have erred
on the side of caution in developing this range, taking two conservative cost
estimates for a preventable ADE that did not include malpractice or litigation
costs, or costs of injuries to patients.
PMID- 29939273
TI - Commentary: War: the mental health costs to our children.
PMID- 29939274
TI - Analysis of multicentre epidemiological studies: contrasting fixed or random
effects modelling and meta-analysis.
AB - Multicentre studies are common in epidemiological research aiming at identifying
disease risk factors. A major advantage of multicentre over single-centre studies
is that, by including a larger number of participants, they allow consideration
of rare outcomes and exposures. Their multicentric nature introduces some
complexities at the step of data analysis, in particular when it comes to
controlling for confounding by centre, which is the focus of this tutorial.
Commonly, epidemiologists use one of the following options: pooling all centre
specific data and adjusting for centre using fixed effects; adjusting for centre
using random effects; or fitting centre-specific models and combining the results
in a meta-analysis. Here, we illustrate the similarities of and differences
between these three modelling approaches, explain the reasons why they may
provide different conclusions and offer advice on which model to choose depending
on the characteristics of the study. Two key issues to examine during the
analyses are to distinguish within-centre from between-centre associations, and
the possible heterogeneity of the effects (of exposure and/or confounders) by
centre. A real epidemiological study is used to illustrate a situation in which
these various options yield different results. A synthetic dataset and R and
Stata codes are provided to reproduce the results.
PMID- 29939275
TI - Potential role of T2Candida in the management of empirical antifungal treatment
in patients at high risk of candidaemia: a pilot single-centre study.
AB - Objectives: We estimated the diagnostic accuracy of T2Candida, with blood culture
(BC) as the gold standard, and compared turnaround time between these two
techniques in order to investigate the potential role of T2Candida in the
management of empirical antifungal treatment (EAT). Methods: We performed a
single-centre prospective observational study in patients with severe sepsis or
septic shock and multiple risk factors for candidaemia. Results: We analysed 46
out of 50 screened patients. All patients received an echinocandin as EAT; the
median EAT duration was 7 days (IQR 4-13 days). BCs were negative in 31 (67.4%)
patients, positive for bacteria in 14 (30.4%) patients and positive for Candida
albicans in 1 (2.2%) patient. T2Candida was negative, invalid and positive in 37,
5 and 4 patients, respectively. T2Candida and BC results were concordant in all
but three patients, where T2Candida was positive and BCs were negative. Two of
them were on antifungal prophylaxis at the time of enrolment. T2Candida reduced
time to a negative result by 5 days. T2Candida performance was: sensitivity =
100% (95% CI 2.5%-100%), specificity = 91.8% (95% CI 78%-98%), positive
predictive value = 25% (95% CI 0.63%-80.6%) and negative predictive value = 100%
(95% CI 89.7%-100%). Conclusions: In patients with multiple risk factors for
candidaemia and severe sepsis or septic shock, T2Candida may be helpful to reduce
the length of EAT.
PMID- 29939276
TI - Not feeling ready to go home: a qualitative analysis of chronically ill patients'
perceptions on care transitions.
AB - Quality problem: Unplanned hospital readmissions frequently occur and have
profound implications for patients. This study explores chronically ill patients'
experiences and perceptions of being discharged to home and then acutely
readmitted to the hospital to identify the potential impact on future care
transition interventions. Initial assessment and implementation: Twenty-three
semistructured interviews were conducted with chronically ill patients who had an
unplanned 30-day hospital readmission at a university teaching hospital in the
Netherlands. Choice of solution: A constructive grounded theory approach was used
for data analysis. Evaluation: The core category identified was 'readiness for
hospital discharge,' and the categories related to the core category are
'experiencing acute care settings' and 'outlook on the recovery period after
hospital discharge.' Patients' readiness for hospital discharge was influenced by
the organization of hospital care, patients' involvement in decision-making and
preparation for discharge. The experienced difficulties during care transitions
might have influenced patients' ability to cope with challenges of recovery and
dependency on others. Lessons learned: The results demonstrated the importance of
assessing patients' readiness for hospital discharge. Health care professionals
are recommended to recognize patients and guide them through transitions of care.
In addition, employing specifically designated strategies that encourage patient
centered communication and shared decision-making can be vital in improving care
transitions and reduce hospital readmissions. We suggest that health care
professionals pay attention to the role and capacity of informal caregivers
during care transitions and the recovery period after hospital discharge to
prevent possible postdischarge problems.
PMID- 29939277
TI - Methylene Blue Treatment of Grafts During Cold Ischemia Time Reduces the Risk of
Hepatitis C Virus Transmission.
AB - Background: Although organ shortage is a rising problem, organs from hepatitis C
virus (HCV) ribonucleic acid (RNA)-positive donors are not routinely transplanted
in HCV-negative individuals. Because HCV only infects hepatocytes, other organs
such as kidneys are merely contaminated with HCV via the blood. In this study, we
established a protocol to reduce HCV virions during the cold ischemic time.
Methods: Standard virological assays were used to investigate the effect of
antivirals, including methylene blue (MB), in different preservation solutions.
Kidneys from mini pigs were contaminated with Jc1 or HCV RNA-positive human
serum. Afterwards, organs were flushed with MB. Hypothermic machine perfusion was
used to optimize reduction of HCV. Results: Three different antivirals were
investigated for their ability to inactivate HCV in vitro. Only MB completely
inactivated HCV in the presence of all perfusion solutions. Hepatitis C virus
contaminated kidneys from mini pigs were treated with MB and hypothermic machine
perfusion without any negative effect on the graft. Human liver-uPA-SCID mice did
not establish HCV infection after inoculation with flow through from these
kidneys. Conclusions: This proof-of-concept study is a first step to reduce
transmission of infectious HCV particles in the transplant setting and might
serve as a model for other relevant pathogens.
PMID- 29939278
TI - Calling and Mating Behavior of Diaphania angustalis (Lepidoptera: Crambidae).
AB - Diaphania angustalis Snellen (Lepidoptera: Crambidae) has emerged as a very
important pest of blackboard tree, Alstonia scholaris (L.) R. Br. (Apocynaceae),
in China during the last two decades. Understanding its biology and behavior is
crucial for designing effective and environmentally friendly pest management
strategies. Under laboratory conditions [25-28 degrees C, 12:12 (L:D) h, 75-80%
RH], adults emerged during both light and dark hours with peak emergence
occurring between the first and fifth hours of scotophase, and unmated males and
females lived for a mean (+/-SE) 5.4 +/- 0.4 and 5.3 +/- 0.7 d, respectively.
Female calling behavior was observed only during scotophase (peaking in the fifth
hour) by 1- to 5-d-old females, and mating activities occurred 2-5 d after
emergence, peaking on day 3. These behavioral characteristics could inform
control programs targeting adults.
PMID- 29939280
TI - Erratum.
PMID- 29939279
TI - IL-1 Antagonism in Men With Metabolic Syndrome and Low Testosterone: A Randomized
Clinical Trial.
AB - Context: Hypogonadism is highly prevalent among obese men with metabolic
syndrome. Chronic low-grade inflammation is suspected to be a major cause for low
testosterone levels in obese individuals. Objectives: To test the inflammatory
hypothesis of testosterone deficiency in metabolic syndrome. Design, Setting,
Participants, and Intervention: In this randomized, placebo-controlled, double
blind trial involving men with metabolic syndrome, we randomly assigned 33
patients to receive 100 mg of anakinra (recombinant human IL-1 receptor
antagonist) subcutaneously twice daily for 4 weeks and 34 patients to receive
placebo. Main Outcome Measures: The primary endpoint was the change from baseline
in total testosterone levels after 4 weeks. Results: The mean age was 54 years
and baseline total testosterone levels were 9.3 nmol/L (95% CI, 8.7 to 10.0). At
4 weeks, total testosterone levels increased by 1.2 nmol/L (95% CI, 0.3 to 2.0; P
= 0.01) in the anakinra group as compared with no change in the placebo group
(0.01 nmol/L; 95% CI, -0.5 to 0.5; P = 0.99), resulting in a between-group
difference of 0.96 nmol/L (95% CI, 0.3 to 1.9; P = 0.04). The effects were most
pronounced with baseline C-reactive protein >2 mg/L (between-group difference
2.14 nmol/L; 95% CI, 0.11 to 4.17; P = 0.04) and body mass index >40 kg/m2
(between-group difference 2.64 nmol/L; 95% CI, 0.19 to 5.09; P = 0.04). Anakinra
treatment did not exert benefits on fatigue and sexual dysfunction, but it
improved grip strength of nondominant hand by 3.5 kg (95% CI 0.23 to 6.81; P =
0.04) and reduced mean arterial blood pressure by 2.9 mm Hg (95% CI, -5.99 to
0.19; P = 0.07). Conclusions: Anti-inflammatory treatment with an antagonist of
IL-1 led to an increase in testosterone levels in obese men with testosterone
deficiency.
PMID- 29939281
TI - Molecular Characterization of a Mitochondrial Manganese Superoxide Dismutase From
Chilo suppressalis (Lepidoptera: Crambidae).
AB - In insects, superoxide dismutases (SODs) play a critical role in the scavenging
of harmful reactive oxygen species (ROS) and protecting against oxidative stress
induced by various environmental stresses. The Asiatic rice borer, Chilo
suppressalis (Walker) (Lepidoptera: Crambidae), is an economically important
insect pest of rice crops. In this study, a mitochondrial manganese SOD (Cs
mMnSOD) gene was characterized in C. suppressalis. The deduced Cs-mMnSOD protein
has typical highly conserved features of mitochondrial manganese SODs, including
four manganese binding residues, the signature DVWEHAYY peptide, and a
mitochondrial-targeting sequence at the N-terminus. Transcription of Cs-mMnSOD
was detectable at all developmental stages, but highest in pupae. Furthermore,
the mRNA level of Cs-mMnSOD was strongly upregulated (more than twofold increase)
following exposure to low and high temperatures (4, 30 and 35 degrees C),
insecticides (chlorpyrifos and chlorantraniliprole), and chemical reagents
(cumene hydroperoxide, paraquat, H2O2 and CdCl2), but slightly elevated (less
than twofold increase) in response to 8 degrees C, abamectin and CuSO4.
Additionally, the Cs-mMnSOD transcription results were consistent with the
enzymatic activity data of the protein product. Purified recombinant Cs-mMnSOD
protein expressed in Escherichia coli displayed SOD activity and thermostability.
Furthermore, E. coli cells overexpressing Cs-mMnSOD exhibited long-term
resistance to the oxidative inducers cumene hydroperoxide and paraquat. Our
findings indicate that Cs-mMnSOD plays an important role in protecting C.
suppressalis against oxidative damage.
PMID- 29939282
TI - Telling the truth about antibiotics: benefits, harms and moral duty in
prescribing for children in primary care.
AB - Antimicrobial resistance represents a growing threat to global health, yet
antibiotics are frequently prescribed in primary care for acute childhood
illness, where there is evidence of very limited clinical effectiveness. Moral
philosophy supports the need for doctors to consider wider society, including
future patients, when treating present individuals, and it is clearly wrong to
waste antibiotics in situations where they are largely clinically ineffective at
the expense of future generations. Doctors should feel confident in applying
principles of antibiotic stewardship when treating children in primary care, but
they must explain these to parents. Provision of accurate, accessible information
about the benefits and harms of antibiotics is key to an ethical approach to
antimicrobial stewardship and to supporting shared decision making. Openness and
honesty about drivers for antibiotic requests and prescribing may further allow
parents to have their concerns heard and help clinicians to develop with them an
understanding of shared goals.
PMID- 29939283
TI - Filling Voids in Subterranean Termite (Blattodea: Rhinotermitidae) Bait Stations
With Soil or Clay Improves Preference and Performance.
AB - Subterranean termites often transport soil into bait stations. In this study, we
hypothesize that adding soil or clay material in the bait may affect preference
and performance of termites. Choice and no-choice tests were conducted in the
laboratory to investigate the aggregation and feeding preference, survivorship,
wood consumption, and body water percentage of termites in response to food
containers (here we simulated the bait station by placing a wood block into a
bigger plastic box with termite-entering holes on the wall) with the void space
filled with soil (sandy clay loam), clay material (sodium bentonite), or remained
unfilled. Choice tests showed that under low-moisture conditions, food containers
filled with clay attracted significantly more termites (Coptotermes formosanus
Shiraki (Blattodea: Rhinotermitidae) and Reticulitermes guangzhouensis Ping
(Blattodea: Rhinotermitidae)) compared to food containers filled with soil, or
unfilled. Under medium-moisture conditions, however, the percentages of termites
that aggregated in the food containers filled with soil or clay were similar, and
both were significant higher than the percentages in unfilled ones. In no-choice
tests, the highest survivorship and wood consumption in C. formosanus were
recorded under medium-moisture conditions and when food containers were filled
with clay, whereas the lowest survivorship and wood consumption were recorded
under low-moisture conditions and when food containers were filled with soil.
Interestingly, presence of clay increased the body water percentage of termites.
Our study enhances the understanding of the foraging ecology of subterranean
termites, and may contribute to the improvement of termite-baiting technologies.
PMID- 29939284
TI - Lessons From the West Africa Ebola Epidemic: A Systematic Review of
Epidemiological and Social and Behavioral Science Research Priorities.
AB - This systematic literature review compared the epidemiological (EPI) research and
the qualitative social and behavioral science (SBS) research published during the
West Africa Ebola virus disease (EVD) epidemic. Beginning with an initial capture
of over 2000 articles, we extracted 236 EPI and 171 SBS studies to examine how
disciplinary priorities affected research conducted during the EVD response, with
implications for epidemic response effectiveness. Building on this research, we
set forth a roadmap for the closer integration of EPI and SBS research in all
aspects of epidemic preparedness and response that incorporates the lessons of
the West Africa EVD outbreak. Key priorities include the following: (1)
developing the capacity to systematically quantify qualitative sociocultural
variables; (2) establishing interdisciplinary collaborations to improve "risk
segmentation" practices; (3) creating and prepositioning qualitative indicators
and composite sociocultural indexes for rapid deployment in outbreaks; (4)
integrating novel systems with community resources; (5) developing new techniques
for modeling social mobilization and community engagement; (6) prioritizing good
data and complex analyses early in emergencies; and (7) learning from past
experiences. Our findings support a program of action that situates data
collection and analysis in real-time, recursive, integrated efforts to move
community attitudes, behaviors, and responses into epidemiological research. We
offer recommendations to improve coordinated, multidisciplinary approaches to
health emergencies.
PMID- 29939286
TI - Susceptibility to price discounting of soda by neighbourhood educational status:
an ecological analysis of disparities in soda consumption using point-of-purchase
transaction data in Montreal, Canada.
AB - Introduction: Price discounting is a marketing tactic used frequently by food
industries and retailers, but the extent to which education modifies the effect
of discounting on the purchasing of unhealthy foods has received little
attention. We investigated whether there was a differential association of price
discounting of soda with store-level soda purchasing records between 2008 and
2013 by store-neighbourhood education in Montreal, Canada. Methods: Using data on
grocery purchase transactions from a sample of supermarkets, pharmacies,
supercentres and convenience stores, we performed an ecological time-series
analysis, modelling weekly store-level sales of soda as a function of store-level
price discounting, store- and neighbourhood-level confounders and an interaction
term between discounting and categorical education in the neighbourhood of each
store. Results: Analysis by store type (n = 18 743, 12 437, 3965 and 49 533 store
weeks for superstores, pharmacies, supercentres and convenience stores,
respectively) revealed that the effect measure modification of discounting by
neighbourhood education on soda purchasing was lower in stores in the more
educated neighbourhoods, most notably in pharmacies: -0.020 [95% confidence
interval (CI): -0.028, -0.012] and -0.038 (95% CI: -0.051, -0.025), for middle-
and high-education categories, respectively). Weaker effect modification was
observed in convenience stores. There was no evidence of effect modification in
supercentres or superstores. Conclusions: Price discounting is an important
environmental risk factor for soda purchasing and can widen education
inequalities in excess sugar intake across levels of education. Interventions to
regulate price discounting warrant further investigation as a public health
strategy to improve population nutrition, particularly in lower-education
neighbourhoods.
PMID- 29939285
TI - Outcome and prognostic factors in metastatic urothelial carcinoma patients
receiving second-line chemotherapy: an analysis of real-world clinical practice
data in Japan.
AB - Objectives: The objective of the present study was to investigate the survival
outcome and prognostic factors of metastatic urothelial carcinoma patients
treated with second-line systemic chemotherapy in real-world clinical practice.
Methods: Overall, 114 patients with metastatic urothelial carcinoma undergoing
second-line systemic chemotherapy were included in this retrospective analysis.
The dominant second-line chemotherapy was a paclitaxel-based combination regimen
(60%, 68/114). We assessed the progression-free survival and overall survival
times using the Kaplan-Meier method. The Cox proportional hazards model was
applied to identify the factors affecting overall survival. Results: The median
progression-free survival and overall survival times were 4 and 9 months,
respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group
performance status score greater than 0 at presentation, C-reactive protein level
?1 mg/dl and poor response to prior chemotherapy were adverse prognostic
indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median
overall survival of 17, 12, 7 and 3 months, respectively. Conclusions: The
Eastern Cooperative Oncology Group performance status at presentation, C-reactive
protein level and response to prior chemotherapy were prognostic factors for
metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In
the future, this information might help guide the choice of salvage treatment,
such as second-line chemotherapy or immune checkpoint inhibitors, after the
failure of first-line chemotherapy.
PMID- 29939288
TI - HDSS Profile: Mlomp Health and Demographic Surveillance System (Mlomp HDSS),
Senegal.
PMID- 29939287
TI - EVI1 carboxy-terminal phosphorylation is ATM-mediated and sustains
transcriptional modulation and self-renewal via enhanced CtBP1 association.
AB - The transcriptional regulator EVI1 has an essential role in early hematopoiesis
and development. However, aberrantly high expression of EVI1 has potent oncogenic
properties and confers poor prognosis and chemo-resistance in leukemia and solid
tumors. To investigate to what extent EVI1 function might be regulated by post
translational modifications we carried out mass spectrometry- and antibody-based
analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the
carboxy-terminal S858/S860 SQS motif. In the presence of genotoxic stress EVI1-WT
(SQS), but not site mutated EVI1-AQA was able to maintain transcriptional
patterns and transformation potency, while under standard conditions carboxy
terminal mutation had no effect. Maintenance of hematopoietic progenitor cell
clonogenic potential was profoundly impaired with EVI1-AQA compared with EVI1-WT,
in particular in the presence of genotoxic stress. Exploring mechanistic events
underlying these observations, we showed that after genotoxic stress EVI1-WT, but
not EVI1-AQA increased its level of association with its functionally essential
interaction partner CtBP1, implying a role for ATM in regulating EVI1 protein
interactions via phosphorylation. This aspect of EVI1 regulation is
therapeutically relevant, as chemotherapy-induced genotoxicity might
detrimentally sustain EVI1 function via stress response mediated phosphorylation,
and ATM-inhibition might be of specific targeted benefit in EVI1-overexpressing
malignancies.
PMID- 29939289
TI - Broad Neutralizing Activity Against Ebolaviruses Lacking the Mucin-Like Domain in
Convalescent Plasma Specimens From Patients With Ebola Virus Disease.
AB - Background: In Ebola virus (EBOV) infection, the specific neutralizing activity
of convalescent plasma against other members of the Ebolavirus genus has not been
extensively analyzed. Methods: We measured the neutralizing activity in plasma
from 3 survivors of the recent outbreak due to the Makona variant of EBOV and
tested its neutralizing potency against other variants of EBOV (ie, Mayinga and
Kikwit) and against Sudan virus (SUDV), Bundibugyo virus (BDBV), and Reston virus
(RESTV), using a glycoprotein (GP)-pseudotyped lentiviral system both with full
length GP and in vitro-cleaved GP (GPCL). Results: Convalescent plasma specimens
from survivors of EBOV infection showed low neutralizing activity against full
length GPs of SUDV, BDBV, RESTV, and EBOV variants Mayinga and Kikwit. However,
broad and potent neutralizing activity was observed against the GPCL forms of
SUDV, BDBV, and RESTV. Discussion: Removal of the mucin-like domain and glycan
cap from the GP of members of the Ebolavirus genus presumably exposes conserved
epitopes in or in the vicinity of the receptor binding site and internal fusion
loop that are readily amenable to neutralization. These types of broad
neutralizing antibodies could be induced by using immunogens mimicking GPCL.
PMID- 29939291
TI - Morphometric Variation of the Aedes albifasciatus (Diptera: Culicidae) Wings in
Three Populations From Different Ecoregions of Argentina.
AB - Shape variability among individuals is important to understand some ecological
relationships, since it provides the nexus between the genotype and the
environment. Geometric morphometrics based on generalized procrustes analysis was
applied on 17 landmarks of the wings of Aedes albifasciatus (Macquart 1838)
(Diptera: Culicidae) females collected from three ecoregions of Argentina (Delta
and islands of the Parana River, Pampa, and Patagonian steppe). This methodology
was used to discriminate the shapes of individuals belonging to different
regions. The population of the Patagonian steppe, which was the most
geographically distant, showed the most dissimilar shape. Different local
variations in wing shape could have been selected according to the environmental
characteristics and maintained by geographic isolation. The individuals of the
two ecoregions closest to each other (Delta and islands of the Parana River and
Pampa) showed differences in shape that can be explained by a lower gene flow due
to the effect of geographic isolation (by the Parana River) and the limited
dispersive capacity of Ae. albifasciatus. The results allow concluding that both
environmental diversity and geographic barriers could contribute to local
variations in wing shape.
PMID- 29939290
TI - Post-transcriptional regulation of Pabpn1 by the RNA binding protein HuR.
AB - RNA processing is critical for proper spatial and temporal control of gene
expression. The ubiquitous nuclear polyadenosine RNA binding protein, PABPN1,
post-transcriptionally regulates multiple steps of gene expression. Mutations in
the PABPN1 gene expanding an N-terminal alanine tract in the PABPN1 protein from
10 alanines to 11-18 alanines cause the muscle-specific disease oculopharyngeal
muscular dystrophy (OPMD), which affects eyelid, pharynx, and proximal limb
muscles. Previous work revealed that the Pabpn1 transcript is unstable,
contributing to low steady-state Pabpn1 mRNA and protein levels in vivo,
specifically in skeletal muscle, with even lower levels in muscles affected in
OPMD. Thus, low levels of PABPN1 protein could predispose specific tissues to
pathology in OPMD. However, no studies have defined the mechanisms that regulate
Pabpn1 expression. Here, we define multiple cis-regulatory elements and a trans
acting factor, HuR, which regulate Pabpn1 expression specifically in mature
muscle in vitro and in vivo. We exploit multiple models including C2C12 myotubes,
primary muscle cells, and mice to determine that HuR decreases Pabpn1 expression.
Overall, we have uncovered a mechanism in mature muscle that negatively regulates
Pabpn1 expression in vitro and in vivo, which could provide insight to future
studies investigating therapeutic strategies for OPMD treatment.
PMID- 29939292
TI - Pea Ferritin Stability under Gastric pH Conditions Determines the Mechanism of
Iron Uptake in Caco-2 Cells.
AB - Background: Iron deficiency is an enduring global health problem that requires
new remedial approaches. Iron absorption from soybean-derived ferritin, an ~550
kDa iron storage protein, is comparable to bioavailable ferrous sulfate (FeSO4).
However, the absorption of ferritin is reported to involve an endocytic
mechanism, independent of divalent metal ion transporter 1 (DMT-1), the
transporter for nonheme iron. Objective: Our overall aim was to examine the
potential of purified ferritin from peas (Pisum sativum) as a food supplement by
measuring its stability under gastric pH treatment and the mechanisms of iron
uptake into Caco-2 cells. Methods: Caco-2 cells were treated with native or
gastric pH-treated pea ferritin in combination with dietary modulators of nonheme
iron uptake, small interfering RNA targeting DMT-1, or chemical inhibitors of
endocytosis. Cellular ferritin formation, a surrogate measure of iron uptake, and
internalization of pea ferritin with the use of specific antibodies were
measured. The production of reactive oxygen species (ROS) in response to
equimolar concentrations of native pea ferritin and FeSO4 was also compared.
Results: Pea ferritin exposed to gastric pH treatment was degraded, and the
released iron was transported into Caco-2 cells by DMT-1. Inhibitors of DMT-1 and
nonheme iron absorption reduced iron uptake by 26-40%. Conversely, in the absence
of gastric pH treatment, the iron uptake of native pea ferritin was unaffected by
inhibitors of nonheme iron absorption, and the protein was observed to be
internalized in Caco-2 cells. Chlorpromazine (clathrin-mediated endocytosis
inhibitor) reduced the native pea ferritin content within cells by ~30%, which
confirmed that the native pea ferritin was transported into cells via a clathrin
mediated endocytic pathway. In addition, 60% less ROS production resulted from
native pea ferritin in comparison to FeSO4. Conclusion: With consideration that
nonheme dietary inhibitors display no effect on iron uptake and the low oxidative
potential relative to FeSO4, intact pea ferritin appears to be a promising iron
supplement.
PMID- 29939293
TI - Surveillance for Ixodes scapularis (Acari Ixodidae) and Borrelia burgdorferi in
Eastern South Dakota State Parks and Nature Areas.
AB - Ixodes scapularis (Acari: Ixodidae) is the principal vector of Borrelia
burgdorferi (the etiologic agent of Lyme disease) in the eastern and midwestern
United States. Recent efforts have documented the first established population of
I. scapularis in South Dakota, representing a western expansion of the known
species distribution. Our goal was to describe the current distribution of I.
scapularis in eastern South Dakota and to survey for the presence of B.
burgdorferi in questing I. scapularis. We surveyed for the presence of adult and
nymphal I. scapularis in seven counties within South Dakota, including 13 locales
from 2016 to 2017. We then tested all I. scapularis, including those collected in
2015 from a previous study, for the presence of B. burgdorferi sensu stricto, via
quantitative and conventional polymerase chain reaction. Here, we document the
presence of I. scapularis in four new counties in South Dakota, and report the
first instance of B. burgdorferi in a questing tick in South Dakota. Coupled with
data from the Centers for Disease Control and Prevention and Companion Animal
Parasite Council our data show that the risk of contracting Lyme disease in South
Dakota is low, but existent and should be an important consideration with regard
to public health, pets, and wildlife.
PMID- 29939294
TI - Antibody Repertoire of Human Polyclonal Antibodies Against Ebola Virus
Glycoprotein Generated After Deoxyribonucleic Acid and Protein Vaccination of
Transchromosomal Bovines.
AB - Several Ebola vaccines and therapeutics are under clinical development. However,
limited knowledge exists on the quality of antibody response generated by
different Ebola vaccines. In this study, antibody repertoire induced by
vaccination of transchromosomal bovine (TcB) with Ebola virus (EBOV) glycoprotein
([GP]; recombinant GP [rGP]) encoded by either deoxyribonucleic acid (DNA) or
nanoparticle-based vaccine platform was analyzed using EBOV genome fragment phage
display library and surface plasmon resonance (SPR)-based real-time kinetics
assay to measure antibody affinity maturation to both native and partially
denatured Ebola GP as well as GP containing the receptor binding domain but
lacking the mucin-like domain. Immunoglobulin (IgG) obtained from rGP
nanoparticle-vaccinated TcB demonstrated ~4-fold higher binding affinity compared
with DNA-vaccinated TcB-induced IgG against the native rGP's. The rGP
nanoparticle vaccine generated a more robust and diverse antibody immune response
to the native EBOV-GP compared with the DNA vaccine, which may explain the
protective efficacy observed for these antibody preparations.
PMID- 29939295
TI - LGP2 virus sensor regulates gene expression network mediated by TRBP-bound
microRNAs.
AB - Here we show that laboratory of genetics and physiology 2 (LGP2) virus sensor
protein regulates gene expression network of endogenous genes mediated by TAR-RNA
binding protein (TRBP)-bound microRNAs (miRNAs). TRBP is an enhancer of RNA
silencing, and functions to recruit precursor-miRNAs (pre-miRNAs) to Dicer that
processes pre-miRNA into mature miRNA. Viral infection activates the antiviral
innate immune response in mammalian cells. Retinoic acid-inducible gene I (RIG-I)
like receptors (RLRs), including RIG-I, melanoma-differentiation-associated gene
5 (MDA5), and LGP2, function as cytoplasmic virus sensor proteins during viral
infection. RIG-I and MDA5 can distinguish between different types of RNA viruses
to produce antiviral cytokines, including type I interferon. However, the role of
LGP2 is controversial. We found that LGP2 bound to the double-stranded RNA
binding sites of TRBP, resulting in inhibition of pre-miRNA binding and
recruitment by TRBP. Furthermore, although it is unclear whether TRBP binds to
specific pre-miRNA, we found that TRBP bound to particular pre-miRNAs with common
structural characteristics. Thus, LGP2 represses specific miRNA activities by
interacting with TRBP, resulting in selective regulation of target genes. Our
findings show that a novel function of LGP2 is to modulate RNA silencing,
indicating the crosstalk between RNA silencing and RLR signaling in mammalian
cells.
PMID- 29939296
TI - Postexposure Efficacy of Recombinant Vesicular Stomatitis Virus Vectors Against
High and Low Doses of Marburg Virus Variant Angola in Nonhuman Primates.
AB - A recombinant vesicular stomatitis virus (rVSV) expressing the Marburg virus
(MARV) Musoke variant glycoprotein fully protects macaques against 2 MARV
variants and Ravn virus as a preventive vaccine and MARV variant Musoke as a
postexposure treatment. To evaluate postexposure efficacy against the most
pathogenic MARV variant, Angola, we engineered rVSVs expressing homologous Angola
glycoprotein. Macaques were challenged with high or low doses of variant Angola
and treated 20-30 minutes after exposure. A total of 25% and 60%-75% of treated
macaques survived the high-dose and low-dose challenges, respectively. The more
rapid disease progression of variant Angola versus variant Musoke may account for
the incomplete protection observed.
PMID- 29939297
TI - The investigation study using a questionnaire about the employment of Japanese
breast cancer patients.
AB - Background: Breast cancer is the most common cancer among women, and its survival
rate has improved. As the number of cancer survivors increases, it is important
to support their social comeback during and after treatment. Methods:
Questionnaires were distributed to breast cancer patients treated in Aichi Cancer
Center Hospital between June and November 2014. Responders were categorized
according to adjuvant therapy (Group A: none, Group B: endocrine therapy, Group
C: chemotherapy), or if they had advanced or recurrent breast cancer (Group D).
Results: A total of 279 patients returned questionnaires (62, 79, 92 and 46
patients in Groups A, B, C and D, respectively). In adjuvant treatment groups, 43
patients (18.5%) quit their job during or after treatment. Most patients had quit
their jobs at the time of diagnosis (7.5%), followed by those undergoing
chemotherapy (5.6%) and those at the time of operation (4.9%). Quit rate from the
workplace in which patients worked at the time of diagnosis was highest in Group
C (30%), followed by Group B (20%) and Group A (13%). At the time of operation,
127 patients (57%) were absent from work. In Group D, 16 patients (35%) quit
their job during treatment. Rates for patients currently working who had anxiety
were 62, 30, 26 and 9% in Groups D, C, B and A, respectively. Conclusions: In
adjuvant treatment groups, in which quit rate was highest at the time of
diagnosis, consultation about working is necessary immediately after diagnosis.
Patients treated most heavily had higher quit rates and experienced more anxiety
about working.
PMID- 29939298
TI - Establishment of Aedes albopictus (Diptera: Culicidae) in the Florida Keys, 2001
2017.
AB - The presence of Aedes albopictus (Skuse) was first reported in the Florida Keys
in 1993. Despite extensive surveillance, the Florida Keys Mosquito Control
District (FKMCD) only collected specimens occasionally on a few islands, some
years finding no evidence of the invasive species. In 2013-2017, FKMCD witnessed
a sudden increase in population size and geographic extent of Ae. albopictus.
Samples of Ae. albopictus have now been identified on 30 different islands in the
Florida Keys. Three islands in particular (Key Largo, Big Pine Key, and Stock
Island) have produced multiple positive samples during at least 4 of the last 5
yr, suggesting establishment of the invasive species. FKMCD continues to monitor
Ae. albopictus throughout the Keys and make extensive efforts to reduce
population abundance and geographic extent of this disease vector.
PMID- 29939299
TI - Surgical Trauma Exacerbates Cognitive Deficits and Neuroinflammation in Aged
Rats: The Role of CX3CL1-CX3CR1 Signaling.
AB - Age is the most prominent risk factor for the development of postoperative
cognitive dysfunction. The present study investigated the role of CX3CL1-CX3CR1
signaling in age-related differences in surgery-induced cognitive deficits and
neuroinflammation. Adult and aged male Sprague-Dawley rats were subjected to
partial hepatectomy or partial hepatectomy with intracerebroventricular infusion
of CX3CL1. On postoperative days 3, 7, and 14, the rats were subjected to an open
field test and the Morris water maze test. Hippocampal interleukin-1beta, CX3CL1,
CX3CR1, brain derived neurotrophic factor (BDNF), ionized calcium-binding adapter
molecule 1 (Iba-1), and Arginase-1 (Arg1) levels were measured. Age exacerbated
cognitive impairment and increased neuroinflammation following surgery. Surgery
induced decreases in CX3CL1 and CX3CR1 proteins were accompanied by increased
microglial activation, as indicated by increased Iba-1 expression. Corresponding
decline in Arg1 and BDNF levels were observed. Treatment with CX3CL1 decreased
proinflammatory cytokines expression, increased BDNF and Arg1 levels in the
brain, and enhanced behavioral recovery. The surgery-induced decreases in CX3CL1
and CX3CR1 expression exacerbated postoperative cognitive deficits and
exaggerated neuroinflammatory responses in this rodent model. Treatment with
CX3CL1 attenuated these effects, at least partly by inhibiting microglial
activation, decreasing the associated production of proinflammatory cytokines,
and enhancing BDNF expression.
PMID- 29939300
TI - High particulate matter 2.5 levels and ambient temperature are associated with
acute lung edema in patients with nondialysis Stage 5 chronic kidney disease.
AB - Background: Numerous studies have shown that exposure to air pollution,
especially particulate matter (PM) with a diameter <2.5 MUm (PM2.5), was
associated with various diseases. We tried to determine the impact of PM2.5 and
other weather factors on acute lung edema in patients with Stage 5 nondialysis
chronic kidney disease (CKD Stage 5-ND). Methods: In total, 317 CKD Stage 5-ND
(estimated glomerular filtration rate 6.79 +/- 4.56 mL/min) patients residing in
central Taiwan who developed acute lung edema and initiated long-term dialysis
were included in this case-crossover study. Pearson's correlation test was used
to examine the relationship of acute lung edema cases with PM2.5 levels and
ambient temperature separately. Results: The average PM2.5 level within the 7-day
period correlated with acute lung edema incidence in the fall [adjusted odds
ratio (OR) 3.23, P = 0.047] and winter (adjusted OR 1.99, P < 0.001). In winter,
even a 3-day exposure to PM2.5 was associated with increased risk (adjusted OR
1.55, P < 0.001). The average temperatures within 3 days in spring and summer
were correlated positively with the risk (adjusted OR 2.77 P < 0.001 and adjusted
OR 2.72, P < 0.001, respectively). In the fall and winter, temperatures were
correlated negatively with the risk (adjusted OR 0.36, P < 0.001 and adjusted OR
0.54, P < 0.001, respectively). Conclusions: A high PM2.5 level was associated
with an increased risk of acute lung edema. High ambient temperature in hot
seasons and low ambient temperature in cold seasons were also associated with
increased risk. It is essential to educate these patients to avoid areas with
severe air pollution and extreme ambient temperature.
PMID- 29939301
TI - Trends in work-related mental disorders by sector in France.
AB - Background: Notifications of work-related mental disorders (WRMDs) are increasing
while little data are available on trends by industrial sector. Aims: To assess
WRMD notifications and trends from 2001 to 2011 by industrial sector using data
collected by the French National Network for Occupational Disease Vigilance and
Prevention (RNV3P) network. Methods: We calculated standardized notification
ratios (SNRs) per sector. To analyse trends over time, we used odds ratios,
analysed by logistic regression, including time as a discrete variable or as a
continuous variable. Results: We found higher than expected WRMD notifications in
manufacturing; paper and book (SNR = 2.16; 95% CI [1.88-2.48]), chemical and
pharmaceutical (SNR = 1.79; 95% CI [1.58-2.03]), textile and clothing (SNR =
1.27; 95% CI [1.04-1.54]). In the trade sectors, retail (SNR = 1.60; 95% CI [1.52
1.68]), motor vehicle and cycle trade and repair (SNR = 1.19; 95% CI [1.05
1.34]). In the services sector personal (SNR = 2.09; 95% CI [1.83-2.38]),
information technology (SNR = 1.54; 95% CI [1.36-1.74]), financial and insurance
(SNR = 1.42; 95% CI [1.31-1.53]), post and telecommunication (SNR = 1.44; 95% CI
[1.30-1.60]), human health and social work (SNR = 1.29; 95% CI [1.24-1.34]). We
found an increase in notifications in agriculture, post-telecommunication
services and the human health/social work sectors and a decrease in
chemical/pharmaceutical, metal, and paper and book manufacturing sectors (P <
0.05). Conclusions: These results reveal trends in notifications for WRMDs by
industrial sector. This highlights the importance of monitoring trends in WRMDs
in specific worker subsets, using specialized networks such as the RNV3P.
PMID- 29939302
TI - Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney
disease patients: a randomized controlled trial.
AB - Background: Microbial-derived uremic toxins, p-cresyl sulfate (PCS), indoxyl
sulfate (IS) and indole 3-acetic acid (IAA), have been associated with the burden
of chronic kidney disease (CKD). Prebiotics have emerged as an alternative to
modulate the gut environment and to attenuate toxin production. This trial aims
to investigate the effect of a prebiotic fructooligosaccharide (FOS) on uremic
toxins of non-dialysis-dependent CKD (NDD-CKD) patients. Methods: A double-blind,
placebo-controlled, randomized trial was conducted for 3 months. In all, 50
nondiabetic NDD-CKD patients [estimated glomerular filtration rate (eGFR) <45
mL/min/1.73 m2], aged 18-80 years, were allocated to prebiotic (FOS, 12 g/day) or
placebo (maltodextrin, 12 g/day) groups. Primary outcomes were changes in serum
(total and free) and urinary (total) PCS. Secondary outcomes included changes in
IS, IAA, serum markers of intestinal permeability (zonulin), gut-trophic factors
(epidermal growth factor and glucagon-like peptide-2), eGFR, inflammation (high
sensitive c-reactive protein and interleukin-6), homeostatic model assessment
insulin resistance, lipid profile and gastrointestinal symptoms. Results: From 50
participants (54% men, 57.3 +/- 14.6 years and eGFR 21.4 +/- 7.6 mL/min/1.73 m2),
46 completed the follow-up. No changes in dietary intake or gastrointestinal
symptoms were observed. There was a trend in the difference of serum total
DeltaPCS (treatment effect adjusted for baseline levels: -12.4 mg/L; 95%
confidence interval (-5.6 to 0.9 mg/L; P = 0.07) and serum-free Delta%PCS
[intervention -8.6 (-41.5 to 13.9%) versus placebo 3.5 (-28.8 to 85.5%); P =
0.07] between the groups. The trend in the difference of serum total DeltaPCS was
independent of eGFR and dietary protein:fiber ratio intake. No difference was
found in urinary PCS. Aside from the decreased high-density lipoprotein
cholesterol in the intervention, no differences were observed in the change of
IS, IAA or other secondary outcome between the groups. Conclusions: Our result
suggests the potential of FOS in reducing serum total and free PCS in nondiabetic
NDD-CKD patients.
PMID- 29939304
TI - The impact of symptoms on health-related quality of life in elderly pre-dialysis
patients: effect and importance in the EQUAL study.
AB - Background: Quality of life (QoL) is an important outcome in chronic kidney
disease (CKD). Patients feel that symptoms are an important determinant of QoL.
However, this relation is unknown. The aims of this study were to investigate the
impact of the number and severity of symptoms on QoL in elderly pre-dialysis
patients, assessed by both the effect of symptoms and their importance relative
to kidney function, and other clinical variables on QoL. Methods: The European
Quality study (EQUAL study) is an ongoing European prospective follow-up study in
late Stage 4/5 CKD patients aged >=65 years. We used patients included between
March 2012 and December 2015. Patients scored their symptoms with the Dialysis
Symptom Index, and QoL with the research and development-36 (RAND-36) item Health
Survey (RAND-36). The RAND-36 results in a physical component summary (PCS) and a
mental component summary (MCS). We used linear regression to estimate the
relation between symptoms and QoL at baseline and after 6 months, and to
calculate the variance in QoL explained by symptoms. Results: The baseline
questionnaire was filled in by 1079 (73%) patients (median age 75 years, 66%
male, 98% Caucasian), and the follow up questionnaire by 627 (42%) patients. At
baseline, every additional symptom changed MCS with -0.81 [95% confidence
interval (CI): -0.91 to -0.71] and PCS with -0.50 (95% CI: -0.62 to -0.39). In
univariable analyses, number of symptoms explained 22% of MCS variance and 11% of
PCS variance, whereas estimated glomerular filtration rate only explained 1%.
Conclusions: In elderly CKD Stage 4/5 patients, symptoms have a substantial
impact on QoL. This indicates symptoms should have a more prominent role in
clinical decision-making.
PMID- 29939305
TI - Sudomotor dysfunction independently predicts incident cardiovascular-renal events
and all-cause death in type 2 diabetes: the Joint Asia Diabetes Evaluation
register.
AB - Background: Early detection and risk factor control prevent chronic kidney
disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may
detect incident cardiovascular-renal events in type 2 diabetes (T2D). Methods:
SUDOSCAN, a non-invasive tool, provides an age-adjusted electrochemical skin
conductance (ESC) composite score incorporating hands/feet ESC measurements, with
a score <=53 indicating sudomotor dysfunction. A consecutive cohort of 2833
Chinese adults underwent structured diabetes assessment in 2012-13; 2028
participants without preexisting cardiovascular disease (CVD) and CKD were
monitored for incident cardiovascular-renal events until 2015. Results: In this
prospective cohort {mean age 57.0 [standard deviation (SD) 10.0] years; median
T2D duration 7.0 [interquartile range (IQR) 3.0-13.0] years; 56.1% men; 72.5%
never-smokers; baseline ESC composite score 60.7 (SD 14.5)}, 163 (8.0%) and 25
(1.2%) participants developed incident CKD and CVD, respectively, after 2.3 years
of follow-up. The adjusted hazard ratios (aHRs) per 1-unit decrease in the ESC
composite score for incident CKD, CVD and all-cause death were 1.02 [95%
confidence interval (CI) 1.01-1.04], 1.04 (1.00-1.07) and 1.04 (1.00-1.08),
respectively. Compared with participants with an ESC composite score >53, those
with a score <=53 had an aHR of 1.56 (95% CI 1.09-2.23) for CKD and 3.11 (95% CI
1.27-7.62) for CVD, independent of common risk markers. When added to clinical
variables (sex and duration of diabetes), the ESC composite score improved
discrimination of all outcomes with appropriate reclassification of CKD risk.
Conclusions: A low ESC composite score independently predicts incident
cardiovascular-renal events and death in T2D, which may improve the screening
strategy for early intervention.
PMID- 29939303
TI - Identification of Combinations of Approved Drugs With Synergistic Activity
Against Ebola Virus in Cell Cultures.
AB - Background: A need to develop therapeutics to treat Ebola virus disease patients
in remote and resource-challenged settings remains in the wake of the 2013-2016
epidemic in West Africa. Toward this goal, we screened drugs under consideration
as treatment options and other drugs of interest, most being small molecules
approved by the Food and Drug Administration. Drugs demonstrating in vitro
antiviral activity were advanced for evaluation in combinations because of
advantages often provided by drug cocktails. Methods: Drugs were screened for
blockade of Ebola virus infection in cultured cells. Twelve drugs were tested in
all (78 pair-wise) combinations, and 3 were tested in a subset of combinations.
Results: Multiple synergistic drug pairs emerged, with the majority comprising 2
entry inhibitors. For the pairs of entry inhibitors studied, synergy was
demonstrated at the level of virus entry into host cells. Highly synergistic
pairs included aripiprazole/piperacetazine, sertraline/toremifene,
sertraline/bepridil, and amodiaquine/clomiphene. Conclusions: Our study shows the
feasibility of identifying pairs of approved drugs that synergistically block
Ebola virus infection in cell cultures. We discuss our findings in terms of the
theoretic ability of these or alternate combinations to reach therapeutic levels.
Future research will assess selected combinations in small-animal models of Ebola
virus disease.
PMID- 29939307
TI - Work-family life conflict and mental well-being.
AB - Background: The promotion and maintenance of workers' mental health is an
increasingly important issue, both for employers and society. Previous research
has shown that job characteristics (i.e. demands, control and support) are
significantly associated with employees' mental well-being. However, changes in
work characteristics have given rise to the emergence of new job demands, leading
to work-family life conflict. Aims: To investigate the association between work
family life conflict and employee mental well-being. Methods: A cross-sectional
study with two samples: one sample comprising clothes store sales employees and
the other comprising call centre operators. Logistic regression models were used
to examine the effects of work-family life conflict on employee well-being.
Results: After controlling for job demands, job control, supervisory support and
co-workers support, work-family life conflict was associated with employee mental
well-being. Conclusions: Work-family life conflict is an important factor to
explain employee well-being and productivity and should be addressed as well as
work factors.
PMID- 29939306
TI - Long-term results of neoadjuvant chemoradiotherapy using cisplatin and 5
fluorouracil followed by esophagectomy for resectable, locally advanced
esophageal squamous cell carcinoma.
AB - This study retrospectively evaluated the long-term results of neoadjuvant
chemoradiotherapy (NCRT) followed by esophagectomy for the patients with
resectable, locally advanced esophageal squamous cell carcinoma (ESCC).
Altogether, 49 patients treated from 2008 to 2012 were analyzed. Chemotherapy
consisted of 5-fluorouracil and cisplatin. Radiotherapy was performed with a
total dose of 40 Gy in 20 fractions for primary tumor, metastatic lymph nodes,
and elective nodal area. Subsequently, transthoracic esophagectomy with extensive
lymphadenectomy was performed. The median follow-up time for the survivors was 86
(range, 55-111) months. Pathological complete response from NCRT was observed in
17 (35%) patients. The 5-year overall survival and relapse-free survival rates
were 56% [95% confidence interval (CI): 43-71%] and 55% (95% CI: 41-69%),
respectively. The 5-year locoregional control rate was 84% (95% CI: 74-95%).
Multivariate analyses revealed body mass index, N-factor, and %DeltaSUVmax as
significant factors for overall survival. Recurrences and within-irradiation
field failure were observed in 16 (31%) and 4 (8%) patients, respectively.
Toxicities of NCRT were generally mild. Postoperative Grade IIIb or worse
complications were seen in 14% of patients, including one Grade V case (2%). The
5-year incidence rate of late complications of Grade 3 or worse was 22% (95% CI:
7-36%). The cumulative 5-year incidence rate of metachronous malignancies was 13%
(95% CI: 1-26%). NCRT followed by esophagectomy for patients with resectable,
locally advanced ESCC showed favorable locoregional control and overall survival,
with acceptable postoperative complications. Long-term careful follow-up for late
complications and metachronous malignancies is needed.
PMID- 29939308
TI - Association of high sensitivity C-reactive protein with diet composition in
Mexican school children.
AB - The high-Sensitivity C-Reactive Protein (hs-CRP) is a cardiovascular riskmarker.
In healthy Mexican children, there islittle evidence that shows any relationship
betweenserum levels of this marker with diet. The objective of this studywas to
associate serumlevels of hs-CRP with the diet composition in Mexican school
children. The cross-sectionalstudy included 300 seemingly healthy children of 10
to 12 years of age, 53.7% were girls and46.3% boys.hs-CRP quantification was
determined by nephelometry. The diet was quantifiedwith a validated food
frequency questionnaire. A descriptive statistical analysis, correlation
andmultivariate regression models were performed by using the SPSS v18
statistical software. Themedian of the hs-CRP was 0.3 mg / L (range: 0.3 to 6.8
mg / L). A significant direct correlationwas found between serum hs-CRP with
protein intake (rho=0.126, p=0.029), total fatty acids(rho = 0.128, p = 0.027)
and saturated fatty acids (rho = 0.159, p = 0.006). hs-CRP was associatedwith the
intake of protein (beta = 0.203, p = 0.037) by multiple regression analysis,
andinversely with whole grains (beta = -0.175, p = 0,002). No significant
association was found withthe rest of the other variables. The serum
concentration of hs-CRP was directly associated withthe consumption of protein,
total and saturated fatty acids and was indirectly proportional withthe
consumption of whole grains.
PMID- 29939310
TI - Specificity of the DNA Mismatch Repair System (MMR) and Mutagenesis Bias in
Bacteria.
AB - The mutation rate of an organism is influenced by the interaction of evolutionary
forces such as natural selection and genetic drift. However, the mutation
spectrum (i.e., the frequency distribution of different types of mutations) can
be heavily influenced by DNA repair. Using mutation-accumulation lines of the
extremophile bacterium Deinococcus radiodurans DeltamutS1 and the model soil
bacterium Pseudomonas fluorescens wild-type and MMR- (Methyl-dependent Mismatch
Repair-deficient) strains, we report the mutational features of these two
important bacteria. We find that P. fluorescens has one of the highest MMR repair
efficiencies among tested bacteria. We also discover that MMR of D. radiodurans
preferentially repairs deletions, contrary to all other bacteria examined. We
then, for the first time, quantify genome-wide efficiency and specificity of MMR
in repairing different genomic regions and mutation types, by evaluating the P.
fluorescens and D. radiodurans mutation data sets, along with previously reported
ones of Bacillus subtilis subsp. subtilis, Escherichia coli, Vibrio cholerae, and
V. fischeri. MMR in all six bacteria shares two general features: 1) repair
efficiency is influenced by the neighboring base composition for both transitions
and transversions, not limited to transversions as previously reported; and 2)
MMR only recognizes indels <4 bp in length. This study demonstrates the power of
mutation accumulation lines in quantifying DNA repair and mutagenesis patterns.
PMID- 29939311
TI - Estimation of the medical need for carbon-ion radiotherapy in Korea.
AB - The Korea Heavy Ion Medical Accelerator project focuses on the development of
medical accelerator facilities for delivering carbon-ion beams to cancer
patients. The purpose of the present study was to estimate the clinical need for
carbon-ion therapy in Korea. Seven tumor sites, namely head and neck, liver,
lung, colon and rectum, prostate, bone and soft tissue, and pancreas were
selected as eligible sites for receiving carbon-ion radiotherapy (RT) by
radiation oncologists of the Korea Institute of Radiological and Medical
Sciences. Cancer incidence data for the selected tumor sites were obtained from
the Korea National Cancer Incidence Database in order to estimate the potential
medical need for carbon-ion RT. The carbon-ion RT adaption rate was assessed
based on the clinical experience of other carbon-ion therapy facilities. An
estimation model was constructed for estimating the medical need for carbon-ion
RT, and from this, 25 606 patients were deemed to be potential candidates for
carbon-ion RT. This estimated potential need corresponded to 10% of newly
diagnosed cancer patients in Korea. The realistic estimation was calculated as
ranging between 4000 and 6300 patients, depending on the carbon-ion RT adaptation
rate. This estimated medical need corresponded to 2-3% of newly diagnosed cancer
patients in Korea. Taken together, our findings suggest that there is a clear
medical need for carbon-ion RT in Korea, with at least 4000 potential patients
per year.
PMID- 29939309
TI - Temperature-induced changes in the wheat phosphoproteome reveal temperature
regulated interconversion of phosphoforms.
AB - Wheat (Triticum ssp.) is one of the most important human food sources. However,
this crop is very sensitive to temperature changes. Specifically, processes
during wheat leaf, flower, and seed development and photosynthesis, which all
contribute to the yield of this crop, are affected by high temperature. While
this has to some extent been investigated on physiological, developmental, and
molecular levels, very little is known about early signalling events associated
with an increase in temperature. Phosphorylation-mediated signalling mechanisms,
which are quick and dynamic, are associated with plant growth and development,
also under abiotic stress conditions. Therefore, we probed the impact of a short
term and mild increase in temperature on the wheat leaf and spikelet
phosphoproteome. In total, 3822 (containing 5178 phosphosites) and 5581
phosphopeptides (containing 7023 phosphosites) were identified in leaf and
spikelet samples, respectively. Following statistical analysis, the resulting
data set provides the scientific community with a first large-scale plant
phosphoproteome under the control of higher ambient temperature. This community
resource on the high temperature-mediated wheat phosphoproteome will be valuable
for future studies. Our analyses also revealed a core set of common proteins
between leaf and spikelet, suggesting some level of conserved regulatory
mechanisms. Furthermore, we observed temperature-regulated interconversion of
phosphoforms, which probably impacts protein activity.
PMID- 29939312
TI - Intestinal barrier disruption and dysregulated mucosal immunity contribute to
kidney fibrosis in chronic kidney disease.
AB - Background: Emerging evidence suggests that intestinal dysbiosis is associated
with diverse pathological processes. In this study we demonstrated intestinal
barrier disruption and aberrant mucosal immunity in 5/6 nephrectomized mice and
the effect of probiotics on chronic kidney disease (CKD). Methods: CKD was
induced in 6-week-old mice by 5/6 nephrectomy. They were fed a lactobacilli
mixture for 8 weeks. Serum, urine and stool samples were collected for renal
function assessments and gut microbiome analyses. Gut permeability, colon heat
shock protein 70 (HSP70) and colon epithelial integrity were evaluated and
cytokine levels in colon and kidney were measured. Colon leukocytes were analyzed
by flow cytometry and bone marrow-derived cells were cocultured with lactobacilli
mixture. Results: In CKD mice, 'leaky gut' was accompanied by decreased colon
HSP70 and claudin-1 expression, whereas it increased pore-forming claudin-2
expression and apoptosis. Although the percentage of regulatory T cells did not
differ between CKD and control mice, cytokine expression and the ratio of
CX3CR1intermediate:CX3CR1high pro-inflammatory/resident macrophages increased in
the colon of CKD mice. Orally administered lactobacilli partially mitigated the
CKD-induced 'leaky gut'; restored colon epithelial HSP70, claudin-1 and claudin-2
expression and decreased apoptosis. Probiotic treatment also restored the
CX3CR1intermediate:CX3CR1high macrophage ratio and increased circular dichroism
(CD)103+CD11c+ regulatory dendritic cells in the colon. These changes suppressed
systemic inflammation and kidney fibrosis. Conclusions: Our results suggest that
intestinal dysbiosis-associated gut barrier disruption and aberrant mucosal
immunity are important for the systemic inflammation and progressive fibrosis of
CKD. Targeting the intestine might provide novel therapeutic opportunities for
CKD.
PMID- 29939313
TI - Rasch measurement in rheumatoid arthritis: deriving psychometrically optimal
measures from the Rasch Everyday Activity Limitation item bank.
AB - Objective: Recently we developed the Rasch Everyday Activity Limitations (REAL)
generic item bank for measuring physical function. In this study we evaluate the
REAL item bank in 209 RA patients and demonstrate how computerized adaptive
testing (CAT) and Optimal Test Assembly methods can be used to derive measures
from the REAL item bank with superior measurement performance compared with the
HAQ Disability Index (HAQ-DI). Methods: Structural validity of the item bank was
assessed using confirmatory factor analysis. The validity of the REAL score
metric in RA was evaluated by examining differential item functioning against the
general population calibration sample. Besides the REAL-CAT, a 6-item short form
(REAL-6) was developed using Optimal Test Assembly that was optimized with
respect to common disability levels in RA, content and reading ease. Measurement
precision of the different instruments was examined using item response theory
methods. Construct validity was evaluated by testing hypothesized correlations
with external measures. Results: Good model-data fit was observed for a one
dimensional model and only two items showed differential item functioning of
substantial magnitude. The REAL-CAT had superior measurement precision compared
with HAQ-DI and REAL-6. REAL-6 outperformed HAQ-DI across all but the very lowest
level of physical function. All three instruments demonstrated good construct
validity (>75% of hypotheses affirmed) and only HAQ-DI had a ceiling effect
(23.9%). Conclusion: This study supports the validity of the REAL item bank and
illustrates the potential of CAT and OTA applications based on the REAL item bank
for assessing physical function in RA.
PMID- 29939314
TI - Safety and Tolerability of Moxifloxacin in Children.
AB - Objectives: Moxifloxacin is not approved by the US Food and Drug Administration
for pediatric use. Although its use might be indicated under certain conditions,
data regarding its safety and tolerability in pediatric patients are limited. The
primary objective of this study was to evaluate the safety of systemic
moxifloxacin therapy in children. Methods: We conducted a retrospective
observational study of patients aged <18 years who received oral or intravenous
moxifloxacin at our institution between January 2011 and July 2016. Patient
demographics, clinical characteristics, indication for moxifloxacin use, and
adverse events (AEs) were extracted via chart review. The attribution of AEs to
moxifloxacin use was adjudicated in consultation with a pediatric infectious
disease (ID) pharmacist. Results: We identified 221 patients who received 300
courses of moxifloxacin. The average age at moxifloxacin initiation was 10.4
years. One or more AEs occurred during 195 (65%) of the courses. Of the 463
distinct AEs, 46 (9.9%) were attributed to moxifloxacin. AEs attributed to
moxifloxacin included corrected QT interval (QTc) prolongation (18 [6%] courses),
transaminase level elevation (7 [2.3%] courses), and increased bilirubin level (3
[1%] courses). AEs led to moxifloxacin discontinuation in 18 (6%) courses. ID
consultation was associated with QTc (P < .001) and transaminase (P = .002)
monitoring. Conclusions: AEs that occur during pediatric moxifloxacin therapy are
relatively common but rarely serious enough to require premature discontinuation.
The drug might be used safely in most children with monitoring, including
evaluation for QTc prolongation, and guidance from ID specialists.
PMID- 29939315
TI - Quality over quantity? Association of skeletal muscle myosteatosis and
myofibrosis on physical function in chronic kidney disease.
AB - Background: Chronic kidney disease (CKD) is characterized by adverse changes in
body composition, which are associated with poor clinical outcome and physical
functioning. Whilst size is the key for muscle functioning, changes in muscle
quality specifically increase in intramuscular fat infiltration (myosteatosis)
and fibrosis (myofibrosis) may be important. We investigated the role of muscle
quality and size on physical performance in non-dialysis CKD patients. Methods:
Ultrasound (US) images of the rectus femoris (RF) were obtained. Muscle quality
was assessed using echo intensity (EI), and qualitatively using Heckmatt's visual
rating scale. Muscle size was obtained from RF cross-sectional area (RF-CSA).
Physical function was measured by the sit-to-stand-60s (STS-60) test, incremental
(ISWT) and endurance shuttle walk tests, lower limb and handgrip strength,
exercise capacity (VO2peak) and gait speed. Results: A total of 61 patients (58.5
+/- 14.9 years, 46% female, estimated glomerular filtration rate 31.1 +/- 20.2
mL/min/1.73 m2) were recruited. Lower EI (i.e. higher muscle quality) was
significantly associated with better physical performance [STS-60 (r = 0.363) and
ISWT (r = 0.320)], and greater VO2peak (r = 0.439). The qualitative rating was
closely associated with EI values, and significant differences in function were
seen between the ratings. RF-CSA was a better predictor of performance than
muscle quality. Conclusions: In CKD, increased US-derived EI was negatively
correlated with physical performance; however, muscle size remains the largest
predictor of physical function. Therefore, in addition to the loss of muscle
size, muscle quality should be considered an important factor that may contribute
to deficits in mobility and function in CKD. Interventions such as exercise could
improve both of these factors.
PMID- 29939316
TI - Design of a clinical risk calculator for major clinical outcomes in patients with
atherosclerotic renovascular disease.
AB - Background: Risk stratification in atherosclerotic renovascular disease (ARVD)
can influence treatment decisions and facilitate patient selection for
revascularization. In this study, we aim to use variables with the best
predictive value to design a risk calculator that can assist clinicians with risk
stratification and outcome prediction. Methods: Patients with a radiological
diagnosis of ARVD referred to our tertiary renal centre were recruited into this
prospective cohort study between 1986 and 2014. Primary clinical endpoints
included: death, progression to end-stage kidney disease and cardiovascular
events (CVE). A stepwise regression model was used to select variables with the
most significant hazard ratio for each clinical endpoint. The risk calculator was
designed using Hypertext Markup Language. Survival and CVE-free survival were
estimated at 1, 5 and 10 years. Results: In total, 872 patients were recruited
into the Salford ARVD study with a median follow-up period of 54.9 months
(interquartile range 20.2-96.0). Only models predicting death and CVE showed good
performance (C-index >0.80). Survival probabilities obtained from the risk
calculator show that most patients with ARVD have reduced long-term survival.
Revascularization improved outcomes in patients with higher baseline estimated
glomerular filtration rate and lower proteinuria but not in those with co
existing comorbidities and higher levels of baseline proteinuria. Conclusions:
Although this risk calculator requires further independent validation in other
ARVD cohorts, this study shows that a small number of easily obtained variables
can help predict clinical outcomes and encourage a patient-specific therapeutic
approach.
PMID- 29939317
TI - Macroglossia and amyloidosis.
PMID- 29939319
TI - Broadening our horizons: are medical humanities an essential part of medical
education?
PMID- 29939318
TI - Role of Antibodies in Protection Against Ebola Virus in Nonhuman Primates
Immunized With Three Vaccine Platforms.
AB - Background: Several vaccine platforms have been successfully evaluated for
prevention of Ebola virus (EBOV) disease (EVD) in nonhuman primates and humans.
Despite remarkable efficacy by multiple vaccines, the immunological correlates of
protection against EVD are incompletely understood. Methods: We systematically
evaluated the antibody response to various EBOV proteins in 79 nonhuman primates
vaccinated with various EBOV vaccine platforms. We evaluated the serum
immunoglobulin (Ig)G titers against EBOV glycoprotein (GP), the ability of the
vaccine-induced antibodies to bind GP at acidic pH or to displace ZMapp, and
virus neutralization titers. The correlation of these outcomes with survival from
EVD was evaluated by appropriate statistical methods. Results: Irrespective of
the vaccine platform, protection from EVD strongly correlated with anti-GP IgG
titers. The GP-directed antibody levels required for protection in animals
vaccinated with virus-like particles (VLPs) lacking nucleoprotein (NP) was
significantly higher than animals immunized with NP-containing VLPs or adenovirus
expressed GP, platforms that induce strong T-cell responses. Furthermore,
protective immune responses correlated with anti-GP antibody binding strength at
acidic pH, neutralization of GP-expressing pseudovirions, and the ability to
displace ZMapp components from GP. Conclusions: These findings suggest key
quantitative and qualitative attributes of antibody response to EVD vaccines as
potential correlates of protection.
PMID- 29939320
TI - Distinct phenotype of kidney stone formers with renal phosphate leak.
AB - Background: Hypercalciuria is the most frequent metabolic disorder encountered in
kidney stone formers (SF). Reduced renal phosphate reabsorption (i.e. renal
phosphate leak) was proposed to be a driver of hypercalciuria in calcium SF.
However, the phenotype of SF with renal phosphate leak remains poorly defined and
the association of renal phosphate leak with stone history, stone composition and
bone mineral density (BMD) has not been studied. Methods: To fill these knowledge
gaps, we conducted a cross-sectional analysis in a cohort of 555 idiopathic
calcareous SF. The ratio of tubular maximum reabsorption of phosphate to
glomerular filtration rate (TmP/GFR) was used to evaluate renal phosphate
transport. Results: Multivariable regression analyses revealed a negative
association of parathyroid hormone (PTH), a positive association of 25-hydroxy
vitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) but no association
of fibroblast growth factor 23 (FGF23) with TmP/GFR. SF with low TmP/GFR had
their first stone event at a younger age and were more likely to have a positive
family history of kidney stones. In addition, urinary calcium excretion and
prevalence of brushite stones were significantly higher in SF with low TmP/GFR.
However, BMD, measured by dual-energy X-ray absorptiometry, was not associated
with TmP/GFR in SF. Conclusions: Renal phosphate handling has a strong heritable
component in SF and correlates with PTH, 25(OH)D and 1,25(OH)2D, but not with
FGF23 levels. Furthermore, a low TmP/GFR (i.e. a renal phosphate leak) is
associated with higher urinary calcium excretion and an increased prevalence of
brushite stones.
PMID- 29939322
TI - OsYSL16 is Required for Preferential Cu Distribution to Floral Organs in Rice.
AB - Deficiency of copper (Cu) causes low fertility in many plant species, but the
molecular mechanisms underlying distribution of Cu to the floral organs are
poorly understood. Here, we found that a member of yellow-stripe like (YSL)
family, YSL16 encoding the Cu-nicotianamine (Cu-NA) transporter, was highly
expressed in the rachilla, with less expression in the palea and lemma of rice
(Oryza sativa). beta-Glucuronidase (GUS) staining of transgenic rice carrying the
OsYSL16 promoter-GUS showed that OsYSL16 was mainly expressed in vascular bundles
of the rachilla as well as the palea and lemma. Knockout of OsYSL16 resulted in
decreased Cu distribution to the stamens, but increased distribution to the palea
and lemma. A short-term (24 h) 65Cu labeling experiment confirmed increased Cu
concentration of palea and lemma in the mutant. Furthermore, we found that
redistribution of Cu from the palea and lemma was impaired in the osysl16 mutant
after exposure to Cu-free solution. The osysl16 mutant showed low pollen
germination, but this was rescued by addition of Cu in the medium. Our results
indicate that OsYSL16 expressed in the vascular bundles of the rachilla is
important for preferential distribution of Cu to the stamens, while OsYSL16 in
vascular bundles of the palea and lemma is involved in Cu redistribution under Cu
limited conditions in rice.
PMID- 29939323
TI - Avoiding hypoglycemia: the use of insulin pump combined with continuous glucose
monitor in type 1 diabetes crossing a Rocky Gorge.
AB - Background: Continuous subcutaneous insulin infusion (CSII) and continuous
glucose monitoring systems (CGMS) have been proven very effective in diabetes
management. Aim: This study evaluated the usefulness of these devices during
prolonged, intense physical activity in an uncontrolled natural environment away
from the clinical research center. Design: Non-randomized, prospective and
observational study. Methods: During the summer, 38 participants with type 1
diabetes crossed the Samaria gorge, the second largest gorge in Europe (17 km).
Twenty subjects on CSII combined with real-time CGMS and 18 on multiple daily
injections (MDI) combined with professional (retrospective) CGMS participated in
the program. All participants were unsupervised during the event. Results: All 38
participants managed to reach the destination point safely. There were no
episodes of severe hypoglycemia. The duration of the exercise (mean +/-SD) was
6.4 +/- 1.3 h. The CSII group exhibited significantly lower hypoglycemic episodes
during exercise (0.1 +/- 0.3 vs. 0.4 +/- 0.6; P = 0.047) as well as lower AUC
below 70 mg/dl compared with the MDI, during the 24 h (0.61 +/- 0.78 vs. 1.84 +/-
1.55; P = 0.007). Individuals on CSII were significantly less likely to develop a
hypoglycemic episode during exercise (P = 0.038). Exercise induced nocturnal
hypoglycemia was not prevented effectively in neither group. Conclusions: CSII
combined with CGMS is effective in controlling blood glucose levels in type 1
diabetics who perform prolonged strenuous exercise. The use of insulin pump
technology in regions with hot Mediterranean climates is safe and can provide
protection against exercise-induced hypoglycemia. Development of precise
instructions for T1DM who occasionally get involved in exercise activities,
requires further studies.
PMID- 29939324
TI - Identification of Genomic and Molecular Traits that Present Therapeutic
Vulnerability to HGF-targeted therapy in Glioblastoma.
AB - Background: Cancer is a complex disease with profound genomic alterations and
extensive heterogeneity. Recent studies on a large-scale genomics have shed
lights on the impact of core oncogenic pathways which are frequently dysregulated
in a wide spectrum of cancer types. Aberrant activation of hepatocyte growth
factor (HGF) signaling axis has been associated with promoting various oncogenic
programs during tumor initiation, progression, and treatment resistance. As a
result, HGF-targeted therapy has emerged as an attractive therapeutic approach.
However, recent clinical trials involving HGF-targeted therapies have
demonstrated rather disappointing results. Thus, an alternative, in-depth
assessment of new patient stratification is necessary to shift the current
clinical course. Methods: To address such challenges, we have evaluated
therapeutic efficacy of YYB-101, a HGF neutralizing antibody, in a series of
primary glioblastoma stem cells (GSCs) both in vitro and in vivo. Furthermore, we
performed genome and transcriptome analysis to determine genetic and molecular
traits that exhibit vulnerability to HGF-mediated therapy. Results: We have
identified differentially expressed genes, including MET, KDR, and SOX3 which are
associated with tumor invasiveness, malignancy, and unfavorable prognosis in
glioblastoma patients. We also demonstrated HGF-MET signaling axis as a key
molecular determinant in GSC invasion and also discovered that a significant
association in HGF expression existed between mesenchymal phenotype and immune
cell recruitment. Conclusions: Up-regulation of MET and mesenchymal cellular
state are essential in generating HGF-mediated therapeutic responses. Our results
provide an important framework for evaluating HGF-targeted therapy in future
clinical settings.
PMID- 29939325
TI - Immune suppression and reversal of the suppressive tumor microenvironment.
AB - Most tumors employ multiple strategies to attenuate T-cell-mediated immune
responses. In particular, immune suppression surrounding the tumor is achieved by
interfering with antigen-presenting cells and effector T cells. Controlling both
the tumor and the tumor microenvironment (TME) is critical for cancer treatment.
Checkpoint blockade therapy can overcome tumor-induced immune suppression, but
more than half of the patients fail to respond to this treatment; therefore, more
effective cancer immunotherapies are needed. Generation of an anti-tumor immune
response is a multi-step process of immune activation against the tumor that
requires effector T cells to recognize and exert toxic effects against tumor
cells, for which two strategies are employed-inhibition of various types of
immune suppressor cells, such as myeloid cells and regulatory T cells, and
establishment of anti-tumor immune surveillance including, activation of natural
killer cells and cytotoxic T cells. It was recently shown that anti-cancer drugs
not only directly kill tumor cells, but also influence the immune response to
cancer by promoting immunogenic cell death, enhancing antigen presentation or
depleting immunosuppressive cells. Herein, we review the mechanisms by which
tumors exert immune suppression as well as their regulation. We then discuss how
the complex reciprocal interactions between immunosuppressive and
immunostimulatory cells influence immune cell dynamics in the TME. Finally, we
highlight the new therapies that can reverse immune suppression in the TME and
promote anti-tumor immunity.
PMID- 29939326
TI - Apparent and standardized ileal digestibility of AA and starch in hybrid rye,
barley, wheat, and corn fed to growing pigs.
AB - An experiment was conducted to determine the apparent ileal digestibility (AID)
of AA and starch and the standardized ileal digestibility (SID) of AA in three
varieties of hybrid rye and in one source of barley, wheat, and corn. Seven
growing barrows (initial BW = 26.1 +/- 2.4 kg) were randomly allotted to a 7 * 7
Latin square design with seven periods and seven experimental diets. Six diets
included one of the grains as the sole source of AA, and an N-free diet was used
to determine basal endogenous losses of CP and AA. In each period, ileal digesta
were collected for 8 h on days 6 and 7 following a 5-d adaptation period. At the
conclusion of the experiment, all ingredients, diets, and ileal digesta samples
were analyzed for starch, CP, and AA. The AID of starch was greater (P < 0.05) in
wheat and corn than in barley or hybrid rye, but all grains had AID values for
starch that were above 95%. Wheat and barley contained more CP and indispensable
AA than hybrid rye, but hybrid rye contained more indispensable AA compared with
corn. The SID of CP and all indispensable AA was greater (P < 0.05) in barley,
wheat, and corn than in the three varieties of rye. However, because of the
greater concentration of AA in hybrid rye than in corn, the quantities of
standardized ileal digestible CP and AA were not different between corn and
hybrid rye. In conclusion, hybrid rye has greater concentrations of most AA than
corn, but the digestibility of AA in rye is less than in other cereal grains. It
is likely that the reason for the reduced SID of AA in rye is that rye contains
more fructans and soluble dietary fiber than other cereal grains, which may
increase viscosity and reduce the efficiency of endogenous peptidases.
PMID- 29939327
TI - ON THE CONVERSION COEFFICIENT FROM AIR KERMA TO AMBIENT DOSE EQUIVALENT VALID FOR
A CS-137 PHOTON FIELD-A CRITICAL REVIEW.
AB - In radiation protection, the quantity ambient dose equivalent, in short H*(10),
is very important in the field of area dosimetry, because this quantity is used
to estimate the effective dose to human beings, whose permissible limits are
restricted by law. The conversion coefficient from air kerma to H*(10), valid for
a 137Cs photon field, is essential as it enters the realization of the quantity
H*(10) as well as every (directly or indirectly) related calibration. The basic
calibration factor of any dose rate instrument is usually related to a
calibration in a 137Cs photon field, which underlines the importance of the
conversion coefficient discussed in this article. Because different values of
this coefficient are used in different calibration facilities, a harmonized best
value will be proposed based on detailed investigations on the origin of the
values recommended in the past. The newly recommended value differs by almost 1%
from the value used by most institutes, at the moment, which is large in
comparison with the typical uncertainties in primary fields. The goal of this
article is to interpret known ICRU/ICRP data adequately, not to calculate new
data.
PMID- 29939328
TI - Reframing Aging: Effect of A Short-Term Framing Intervention on Implicit Measures
of Age Bias.
AB - Objectives: Evidence suggests that ageist biases may operate implicitly (i.e.
automatically and unconsciously) to affect discriminatory attitudes and behaviors
toward older adults. However, few studies have tested the malleability of
implicit age bias. The present study tests the effect of a framing intervention
on implicit age bias in a nationally-representative sample of American adults.
Method: Participants (N=767) were randomly assigned to read one of three framed
messages, to an unframed message about aging, or to a control message unrelated
to aging. Framed messages emphasized (i) the contributions of older adults to
society; (ii) aging as a process of accumulating wisdom and energy; (c)
mechanisms through which prejudice against older adults operates. Participants
subsequently completed an Aging Implicit Association Test (IAT) to assess
implicit bias. Results: Relative to the control condition, participants in the
three framed message conditions displayed lower implicit age bias. No differences
were observed between participants in the control condition and those who read
the unframed message. Discussion: Findings indicate that reframing messages about
aging can decrease implicit bias against older adults. This study highlights ways
for communicators to promote a positive understanding of the aging process,
thereby mitigating sources of implicit prejudice.
PMID- 29939329
TI - 'Modernization of Our Hospital System': The National Health Service, the Hospital
Plan, and the 'Harness' Programme, 1962-77.
AB - This article augments the literature on the British experience of planning by
examining attempts to plan the hospital system between 1962 and 1977. The
Hospital Plan for England and Wales of 1962 proposed the construction of a suite
of new 'District General Hospitals'. Underpinning this proposal was a belief in
the value of standardized designs and construction methods, both of which were
subsequently investigated in detail by the Ministry of Health and the Department
of Health and Social Security (DHSS). The history of this project reveals the
challenges of putting centralized planning into practice. Yet while the
standardization programme was scaled back in 1975, the article suggests that the
drive to 'plan' modern Britain perhaps lasted longer than might initially be
thought, into the 1980s, with implications for the way that the broader history
of this period is framed.
PMID- 29939330
TI - Evaluation of a Train-the-trainer Program to Build Capacity for Training Tobacco
Treatment Specialists.
AB - Introduction: Tobacco treatment specialists (TTSs) and high quality TTS training
programs are needed to improve access to evidence-based tobacco dependence
treatment. To meet this demand, the University of Massachusetts (UMass) Medical
School developed the Train the Trainer in Tobacco Treatment (T4) program to build
a cadre of trainers to deliver the accredited UMass TTS training programs. This
paper reports on the feasibility and quality of TTS trainings led by Certified
UMass TTS Trainers (Trainer-led) compared with trainings led by UMass staff (On
site). Methods: Data were collected between September 2014 and June 2017.
Feasibility included the number of Trainers, Trainer-led programs and
participants. Quality compared participant exam results and evaluations of the
two training program types. Results: Fifty-three Trainers were certified during
2014-2017, and conducted 26 TTS trainings with 351 participants. There were no
significant differences in participant mean exam scores [On-site=86.33 (SD=7.83);
Trainer-led=86.15 (SD=8.47)], and a similar percentage of participants obtained a
passing score on the exam (On-site 94.4%, Trainer-led 94.0%). There were no
significant differences in increased self-efficacy in delivering effective
tobacco treatment services [On-site=2.92, Trainer-led=2.93; p=0.52 (3-point
Likert scale, 1=not at all, 3=a great deal)] or in overall satisfaction with the
training [On-site=3.84; Trainer-led=3.81; p=.072 (4-point Likert scale, 1=very
dissatisfied, 4=very satisfied)]. Conclusions: The Trainer-led model expanded the
number of UMass-trained TTSs with equivalent participant knowledge and perceived
improvement in ability to deliver effective tobacco dependence treatment compared
to the gold-standard training model. It offers a potentially more accessible
option for training TTSs compared to the On-site model. Implications: Train the
Trainer in Tobacco Treatment (T4) has increased the capacity to deliver high
quality training to healthcare providers who might not otherwise have access to
an accredited Tobacco Treatment Specialist training program. Certified Trainers
effectively identified potential participants and delivered training that was
equivalent in quality to the standard UMass TTS Core Training program. There were
no significant differences between the training models in two critical measures:
1) participant exam scores, and 2) participants' rating of improvement in their
ability to deliver effective tobacco dependence treatment. Organizations can now
choose from two equally effective models for delivering TTS training based on
their unique needs and training populations.
PMID- 29939332
TI - Brennan GP, Hunter SJ, Snow G, Minick KI. Responsiveness to change of functional
limitation reporting: cross-sectional study using the Intermountain ROMS Scale in
outpatient rehabilitation. Phys Ther. 2017;97:1182-1189.
PMID- 29939331
TI - Don't Assume the Control Group Is Normal-People with Asymptomatic Tendon
Pathology Have Higher Pressure Pain Thresholds.
AB - Objective: Pain pressure thresholds (PPT) are used to study peripheral and
central pain processing. In the tendon, pathological changes may exist without
pain. This pilot study aimed to compare PPT between individuals with normal
tendons and asymptomatic tendon pathology, and between individuals with and
without a history of tendon pain. Methods: The patellar, Achilles, and
supraspinatus tendons of 128 asymptomatic participants were examined with
ultrasound. Global PPT average was determined using a digital algometer at the
patellar tendon, quadriceps muscle, L3 spinous process, and deltoid muscle
insertion. Participants were separated into three groups: (1) healthy control
group (no pathology, no history of pain), (2) tendon pathology at any site
without a history of pain, (3) history of tendon pain anywhere. Results: There
were 92 controls, seven with asymptomatic pathology and 29 with a history of
tendon pain. Asymptomatic tendon pathology at any site (without a history of
pain) was associated with globally increased PPTs compared with controls (P <
0.001, pathology N = 7, N = 92 controls). Matched pair analysis remained
significant (P < 0.004). A history of tendon pain was associated with globally
increased PPTs compared with the control group (P = 0.026). Matched pair analysis
was not significant (P = 0.122). Conclusions: Asymptomatic tendon pathology is
associated with higher PPTs. These findings point toward central nervous system
adaptations but in a novel way-central desensitization. This challenges the
validity of conclusions drawn from PPT studies that do not verify normal
structure in the control group; artificial inflation of control group data may
incorrectly indicate decreased PPTs in the comparison group.
PMID- 29939333
TI - Scholarships, Fellowships, and Grants.
PMID- 29939334
TI - Erratum.
PMID- 29939336
TI - Optimising diagnostic strategies in emphysematous osteomyelitis.
PMID- 29939335
TI - The resilient brain: psychological resilience mediates the effect of amplitude of
low-frequency fluctuations in orbitofrontal cortex on subjective well-being in
young healthy adults.
AB - Psychological resilience reflects the capacity to bounce back from stress, which
plays an important role in health and well-being. However, less is known about
the neural substrate for psychological resilience and the underlying mechanism
for how psychological resilience enhances subjective well-being in the healthy
brain. To investigate these issues, we employed fractional amplitude of low
frequency fluctuations (fALFF) measured with resting-state fMRI in 100 young
healthy adults. The correlation analysis found that higher psychological
resilience was related to lower fALFF in the left orbitofrontal cortex (OFC),
which is involved in reward-related processing and emotion regulation.
Furthermore, the mediation analysis indicated that psychological resilience acted
as a full mediator of the association between the fALFF in left OFC and
subjective well-being indicators (i.e. life satisfaction and hedonic balance).
Importantly, these results remained significant after controlling for the effect
of gray matter volume and regional homogeneity in the region. Overall, the
present study provides the further evidence for functional neural substrates of
psychological resilience and reveals a potential mechanism that psychological
resilience mediates the effect of spontaneous brain activity on subjective well
being.
PMID- 29939337
TI - Impact of Perfluorooctane Sulfonate on Reproductive Ability of Female Mice
through Suppression of Estrogen Receptor alpha-Activated Kisspeptin Neurons.
AB - Perfluorooctane sulfonate (PFOS) is used extensively in industrial and household
applications. High exposure to PFOS has been associated with increased odds of
irregular and long menstrual cycles in women. However, the underlying mechanisms
remain to be elucidated. Herein, we show that adult female mice appeared
prolongation of diestrus and reduction of corpora luteum within a week of oral
administration of PFOS (10 mg/kg), which are associated with decreases in the
levels of serum progesterone, LH and hypothalamic GnRH. The number of AVPV
kisspeptin neurons and the AVPV-kisspeptin expression were increased in proestrus
mice or OVX-mice treated with high-dose estradiol benzoate (0.05 mg/kg), which
were suppressed by the administration of PFOS. The administration of PFOS or
GPR54 antagonist P234 prevented the generation of LH-surge in OVX-mice treated
with high-dose E2. In hypothalamic slices incubated in 100 nM E2 for 4 h, the
AVPV-kisspeptin expression was significantly enhanced, which was inhibited by
PFOS in a dose-dependent manner or estrogen receptor alpha (ERalpha) antagonist
MPP, but not ERbeta antagonist PHTPP. The incubation of ERalpha agonist PPT
rather than ERbeta agonist DPN could increase the level of AVPV-kisspeptin
expression, which was sensitive to the treatment with PFOS. The administration of
GPR54 agonist kisspeptin-10 in PFOS-mice could correct the prolongation of
diestrus and reduction of corpora luteum, and recover the LH-surge and the levels
of LH and GnRH. The results indicate that exposure to PFOS suppressed ERalpha
induced activation of AVPV-kisspeptin neurons leads to diestrus prolongation and
ovulation reduction.
PMID- 29939338
TI - Disconnected and Hyperactive: A Replication of Sensorimotor Cortex Abnormalities
in Patients With Schizophrenia During Proactive Response Inhibition.
AB - Inhibitory failure represents a core dysfunction in patients with schizophrenia
(SP), which has predominantly been tested in the literature using reactive (ie,
altering behavior after a stimulus) rather than proactive (ie, purposefully
changing behavior before a stimulus) response inhibition tasks. The current study
replicates/extends our previous findings of SP exhibiting sensorimotor cortex
(SMC) hyperactivity and connectivity abnormalities in independent samples of
patients and controls. Specifically, 49 clinically well-characterized SP and 54
matched healthy controls (HC) performed a proactive response inhibition task
while undergoing functional magnetic resonance imaging and resting-state data
collection. Results indicated that the majority of SP (84%) and HC (88%)
successfully inhibited all overt motor responses following a cue, eliminating
behavioral confounds frequently present in this population. Observations of left
SMC hyperactivity during proactive response inhibition, reduced cortical
connectivity with left SMC, and increased connectivity between left SMC and
ventrolateral thalamus were replicated for SP relative to HC in the current
study. Similarly, negative symptoms (eg, motor retardation) were again associated
with SMC functional and connectivity abnormalities. In contrast, findings of a
negative blood oxygenation level-dependent response in the SMC of HC did not
replicate. Collectively, current and previous findings suggest that SMC
connectivity abnormalities may be more robust relative to evoked hemodynamic
signals during proactive response inhibition. In addition, there is strong
support that these SMC abnormalities are a key component of SP pathology, along
with dysfunction within other sensory cortices, and may be associated with
certain clinical deficits such as negative symptoms.
PMID- 29939339
TI - VEGF-C sustains VEGFR2 activation under bevacizumab therapy and promotes
glioblastoma maintenance.
AB - Background: Glioblastoma ranks among the most lethal cancers, with current
therapies offering only palliation. Paracrine vascular endothelial growth factor
(VEGF) signaling has been targeted using anti-angiogenic agents, whereas
autocrine VEGF/VEGF receptor 2 (VEGFR2) signaling is poorly understood.
Bevacizumab resistance of VEGFR2-expressing glioblastoma cells prompted
interrogation of autocrine VEGF-C/VEGFR2 signaling in glioblastoma. Methods:
Autocrine VEGF-C/VEGFR2 signaling was functionally investigated using RNA
interference and exogenous ligands in patient-derived xenograft lines and primary
glioblastoma cell cultures in vitro and in vivo. VEGF-C expression and
interaction with VEGFR2 in a matched pre- and post-bevacizumab treatment cohort
were analyzed by immunohistochemistry and proximity ligation assay. Results: VEGF
C was expressed by patient-derived xenograft glioblastoma lines, primary cells,
and matched surgical specimens before and after bevacizumab treatment. VEGF-C
activated autocrine VEGFR2 signaling to promote cell survival, whereas targeting
VEGF-C expression reprogrammed cellular transcription to attenuate survival and
cell cycle progression. Supporting potential translational significance,
targeting VEGF-C impaired tumor growth in vivo, with superiority to bevacizumab
treatment. Conclusions: Our results demonstrate VEGF-C serves as both a paracrine
and an autocrine pro-survival cytokine in glioblastoma, promoting tumor cell
survival and tumorigenesis. VEGF-C permits sustained VEGFR2 activation and tumor
growth, where its inhibition appears superior to bevacizumab therapy in improving
tumor control.
PMID- 29939341
TI - Optimal rates for phylogenetic inference and experimental design in the era of
genome-scale datasets.
AB - With the rise of genome- scale datasets there has been a call for increased data
scrutiny and careful selection of loci appropriate for attempting the resolution
of a phylogenetic problem. Such loci are desired to maximize phylogenetic
information content while minimizing the risk of homoplasy. Theory posits the
existence of characters that evolve under such an optimum rate, and efforts to
determine optimal rates of inference have been a cornerstone of phylogenetic
experimental design for over two decades. However, both theoretical and empirical
investigations of optimal rates have varied dramatically in their conclusions:
spanning no relationship to a tight relationship between the rate of change and
phylogenetic utility. Here we synthesize these apparently contradictory views,
demonstrating both empirical and theoretical conditions under which each is
correct. We find that optimal rates of characters-not genes-are generally robust
to most experimental design decisions. Moreover, consideration of site rate
heterogeneity within a given locus is critical to accurate predictions of
utility. Factors such as taxon sampling or the targeted number of characters
providing support for a topology are additionally critical to the predictions of
phylogenetic utility based on the rate of character change. Further, optimality
of rates and predictions of phylogenetic utility are not equivalent,
demonstrating the need for further development of comprehensive theory of
phylogenetic experimental design.
PMID- 29939340
TI - Brain structural thickness and resting state autonomic function in adolescents
with major depression.
AB - Major depressive disorder (MDD) has been associated with abnormalities in
cortical thickness and autonomic function. Adolescence is a time notable for
brain development and MDD onset. In healthy adolescents, greater resting state
vagal activity (RVA) is associated with lower cortical thickness. The
relationship between brain structural thickness and RVA in adolescents with MDD
has not previously been studied. This secondary analysis drew on a sample of 37
non-depressed controls and 53 adolescents with MDD. Resting state heart rate and
two indices of RVA (HF-HRV and RMSSD) were recorded during a neuroimaging
session. Cortical thickness within fronto-limbic regions of interest was measured
using Freesurfer analysis of T1-weighted high-resolution structural images. Self
reports of depression severity showed a significant interaction with cortical
thickness of the right insula in predicting RMSSD [t = 2.22, P=0.030, beta =
5.44; model fit of the interaction term as indicated by the 'Bayes Factor' (BF):
7.58] and HF-HRV (t = 2.09, P=0.041, beta = 4.72; BF: 7.94). Clinician ratings of
depression severity showed further interactions. Findings underscore the
important relationships between RVA and cortical development, suggesting two
possible explanations: (i) in adolescent MDD, greater fronto-limbic thickness is
compensatory for deficits in autonomic regulation or (ii) increased autonomic
arousal results in delayed fronto-limbic maturation. Longitudinal research is
necessary to further clarify the nature of the relationship between autonomic
functioning and cortical development.
PMID- 29939342
TI - The Organophosphorus Pesticide Chlorpyrifos Induces Sex-Specific Airway
Hyperreactivity in Adult Rats.
AB - Occupational and environmental exposures to organophosphorus pesticides (OPs) are
associated with increased incidence of asthma and other pulmonary diseases.
Although the canonical mechanism of OP neurotoxicity is inhibition of
acetylcholinesterase (AChE), it was previously reported that the OP chlorpyrifos
(CPF) causes airway hyperreactivity (AHR) in guinea pigs at levels that do not
inhibit lung or brain AChE. The guinea pig is considered to have inherently
hyperresponsive airways, thus, cross-species validation is needed to confirm
relevance to humans. Additionally, sex differences in asthma incidence have been
demonstrated in the human population, but whether OP-induced AHR is sex-dependent
has not been systematically studied in a preclinical model. In this study, 8-week
old male and female Sprague Dawley rats were administered CPF at doses causing
comparable AChE inhibition in whole lung homogenate (30 mg/kg in males, 7 mg/kg
in females, sc) prior to assessing pulmonary mechanics in response to electrical
stimulation of the vagus nerves at 24 h, 48 h, 72 h, 7 d or 14 d post-exposure in
males, and 24 h or 7 d post-exposure in females. CPF significantly potentiated
vagally induced airway resistance and tissue elastance at 7 d post-exposure in
males, and at 24 h and 7 d post-exposure in females. These effects occurred
independent of significant AChE inhibition in cerebellum, blood, trachealis, or
isolated airway, suggesting that AChE independent OP-induced airway
hyperreactivity is a cross-species phenomenon. These findings have significant
implications for assessing the risk posed by CPF, and potentially other OPs, to
human health and safety.
PMID- 29939343
TI - The Role of Movement Specific Reinvestment in vIsuo-motor Control of Walking by
Older Adults.
AB - Objectives: The aim of this study was to examine the association between
conscious monitoring and control of movements (i.e., movement specific
reinvestment) and visuo-motor control during walking by older adults. Method: The
Movement Specific Reinvestment Scale (MSRS; Masters, Eves, & Maxwell, 2005) was
administered to ninety-two community-dwelling older adults, aged 65-81 years, who
were required to walk along a 4.8-meter walkway and step on the middle of a
target as accurately as possible. Participants' movement kinematics and gaze
behavior were measured during approach to the target and when stepping on it.
Results: High scores on the MSRS were associated with prolonged stance and double
support times during approach to the stepping target, and less accurate foot
placement when stepping on the target. No associations between MSRS and gaze
behavior were observed. Discussion: Older adults with a high propensity for
movement specific reinvestment seem to need more time to "plan" future stepping
movements, yet show worse stepping accuracy than older adults with a low
propensity for movement specific reinvestment. Future research should examine
whether older adults with a higher propensity for reinvestment are more likely to
display movement errors that lead to falling.
PMID- 29939344
TI - Stereotype-based stressors facilitate emotional memory neural network
connectivity and encoding of negative information to degrade math self
perceptions among women.
AB - Stress engendered by stereotype threatening situations may facilitate encoding of
negative, stereotype confirming feedback received during a performance among
women in science, technology, engineering and mathematics (STEM). It is unclear,
however, whether this process is comprised of the same neurophysiological
mechanisms evident in any emotional memory encoding context, or if this encoding
bias directly undermines positive self-perceptions in the stigmatized domain. A
total of 160 men and women completed a math test that provided veridical positive
and negative feedback, a memory test for feedback, and math self-enhancing and
valuing measures in a stereotype threatening or neutral context while continuous
electroencephalography activity and startle probe responses to positive and
negative feedback was recorded. Indexing amygdala activity to feedback via
startle responses and emotional memory network connectivity elicited during
accurate recognition of positive and negative feedback via graph analyses, only
stereotype threatened women encoded negative feedback better when they exhibited
increased amygdala activity and emotional memory network connectivity in response
to said feedback. Emotional memory biases, in turn, predicted decreases in
women's self-enhancing, math valuing and performance. Findings provide an
emotional memory encoding-based mechanism for well-established findings
indicating that women have more negative math self-perceptions compared with men
regardless of actual performance.
PMID- 29939346
TI - Response to Dr. Jolobe: "Optimising diagnostic strategies in emphysematous
osteomyelitis".
PMID- 29939345
TI - Assault-related self-blame and its association with PTSD in sexually assaulted
women: an MRI inquiry.
AB - Sexual assault is a frequent interpersonal trauma, which often leads to post
traumatic stress disorder (PTSD). Among other postassault characteristics, self
blame attributions were suggested to play an important role in sexually assaulted
individuals' coping and were consistently associated with PTSD in this
population. The present study aimed to elucidate the neural underpinnings that
may associate self-blame and PTSD in women who experienced sexual assault at
adulthood, using structural and resting-state functional MRI. Thirty-eight
sexually assaulted women and 24 non-exposed matched controls were studied (mean
age: 25 years). Among the sexually assaulted participants, assault-related self
blame was negatively correlated with gray matter volume (GMV) bilaterally in the
lingual gyrus and adjacent intracalcarine cortex. GMV in this cluster was also
predicted by intrusion symptoms and negative social reactions. Resting-state
functional connectivity (rs-FC) of this cluster with the left anterior temporal
fusiform cortex significantly differed between PTSD and non-PTSD sexually
assaulted participants, and was inversely correlated with intrusion symptoms and
with peritraumatic dissociation. Finally, lingual cluster's GMV and rs-FC with
the anterior fusiform mediated the association between self-blame and intrusion
symptoms across sexually assaulted participants. These findings link assault
related self-blame, disrupted postassault recovery and the neural circuitry
involved in the processing of traumatic memories.
PMID- 29939347
TI - OX40 ligand is inhibitory during the effector phase of crescentic
glomerulonephritis.
AB - Background: The functional relevance of OX40 ligand (OX40L) in the effector phase
of crescentic glomerulonephritis (GN) is unknown. These studies defined the role
of endogenous OX40L during the effector stage of murine crescentic GN. Methods:
GN was induced by immunization with sheep globulin/adjuvant on Day 0 and
injection of sheep anti-mouse glomerular basement membrane immunoglobulin (Ig) on
Day 10. Rat IgG or neutralizing anti-OX40L antibody was administered on Days 10
18 and immune responses and renal injury assessed on Day 20. Results: Compared
with naive animals, OX40L was upregulated in the lymph nodes (LNs) and on
leucocytes and resident non-immune cells in the kidneys of mice with GN.
Inhibition of OX40L in GN augmented renal injury, as indicated by increased
crescent formation, proteinuria and glomerular leucocyte accumulation. In line
with increased injury, anti-OX40L treatment increased proliferation and decreased
apoptosis of CD4 T cells in the LNs, without affecting LN CD4 cytokine production
and CD8 T-cell responses. Blockade of OX40L decreased LN regulatory T-cell (Treg)
proliferation, transforming growth factor beta production and foxp3 expression.
OX40L inhibition did not affect B cell expansion or circulating antibody levels.
In the kidney, neutralization of OX40L augmented interferon gamma (IFNgamma)
expression by CD4 and CD8 T cells and shifted macrophage polarization towards the
pro-inflammatory M1 phenotype. Conclusions: OX40L is protective during the
effector phase of murine crescentic GN by reducing the expansion of CD4 T cells
and enhancing Treg responses in the LNs, and by locally inhibiting T-cell
IFNgamma production and pro-inflammatory macrophage phenotype in the kidney.
PMID- 29939348
TI - Genetically high plasma vitamin C and urate: a Mendelian randomization study in
106 147 individuals from the general population.
AB - Objective: Gout is the most common form of inflammatory arthritis and is caused
by hyperuricaemia. Some studies have found a reduction in plasma urate with
vitamin C supplementation. We tested the hypothesis that high plasma vitamin C is
causally associated with low plasma urate and low risk of hyperuricaemia, using a
Mendelian randomization approach. Methods: We measured plasma urate and genotyped
for the SLC23A1 rs33972313 vitamin C variant in 106 147 individuals from the
Copenhagen General Population Study, of which 24 099 had hyperuricaemia. We
measured plasma vitamin C in 9234 individuals and genotyped for the SLC2A9
rs7442295 urate variant in 102 345 individuals. Results: Each 10 umol/l higher
plasma vitamin C was associated with a -2.3(95%CI: -0.69 to -3.9) umol/l lower
plasma urate after multivariable adjustments. The SLC23A1 rs33972313 GG genotype
was associated with a 9% (5.6%, 11.9%) higher plasma vitamin C compared with AA
and AG combined but was not associated with plasma urate (P = 0.31). Likewise,
for each 10 umol/l higher plasma vitamin C the odds ratios for hyperuricaemia
were 0.92 (0.86, 0.98) observationally after multivariable adjustments, but 1.01
(0.84, 1.23) genetically. Conclusion: High plasma vitamin C was associated with
low plasma urate and with low risk of hyperuricaemia. However, the SLC23A1
genetic variant causing lifelong high plasma vitamin C was not associated with
plasma urate levels or with risk of hyperuricaemia. Thus, our data do not support
a causal relationship between high plasma vitamin C and low plasma urate.
PMID- 29939349
TI - "Brain Connectivity Deviates by Sex and Hemisphere in the First Episode of
Schizophrenia"-A Route to the Genetic Basis of Language and Psychosis?
AB - Schizophrenia is genetic in origin and associated with a fecundity disadvantage.
The deficits in schizophrenia have been attributed to variation related to the
human capacity for language or brain laterality. How sex influences the relative
connectivity of the 2 hemispheres is a route to understanding these 2 functions.
Using resting-state functional magnetic resonance imaging (fMRI) we searched for
sex- and hemisphere-specific changes in whole-brain functional-connectivity in
multi-site datasets (altogether 672 subjects including 286 patients, all right
handed) in the first-episode schizophrenia (illness duration <= 1 year, mostly
drug naive) and in chronic stages of schizophrenia (illness duration > 1 year),
respectively. We used meta-analyses to integrate data from different sources
concerning individuals at the same illness stage. We found first-episode male
patients are predominantly left-lateralized in aberrant connectivity with a focus
on Broca's area. Female patients show a lesser degree of lateralization than
males, but to the right particularly in orbital frontal cortex. In the chronic
stage, the focus of aberrant connectivity shifted from anterior to posterior
structures with prominent involvement of the thalamus and pre- and post-central
gyri bilaterally and in both sexes. While the "deviant connectivity" is right
sided in both the first-episode and the chronic stages in females, in males there
is a shift between stages from the left to the right hemisphere. We hypothesized
that the pathophysiology of schizophrenia may lie in the interaction between sex
and lateralization, ie, in genetic mechanisms located on the X and Y chromosomes,
intrinsic to the evolution of language.
PMID- 29939351
TI - Intensity Specific Repetitive Mild Traumatic Brain Injury Evokes an Exacerbated
Burden of Neocortical Axonal Injury.
AB - Mild traumatic brain injury (mTBI) has been linked to enduring neurological
damage following repetitive injury. Previously, we reported that intensity
specific, repetitive mTBI exacerbated microvascular and axonal damage in
brainstem. For a more rigorous and global assessment, we assessed the burden of
neocortical diffuse axonal injury (DAI) evoked by repetitive mTBI. Mice were
subjected to mild central fluid percussion injuries at 1.4 and 1.6 atm with or
without repetitive insult at a 3-hour interval and killed at 24 hours postinjury.
Neocortical DAI within layer V was quantitatively assessed by double-labeling p-c
Jun and NeuN to identify both the axotomized and total neuronal population. Both
confocal and electron microscopic findings revealed no apparent evidence of
neuronal death. Repetitive mTBI of 1.6 atm group, but not of 1.4 atm group,
demonstrated a significantly higher proportion of axotomized neurons. These
results demonstrate that different intensities of mTBI induced different burdens
of DAI after repetitive insult. Interestingly, the parallel loss of the righting
reflex reflected differences in injury intensity, yet the duration of this reflex
was not elongated by the repetitive insult. These data highlight some of the
complex issues surrounding repetitive mTBI and its associated morbidity,
mandating the need for continued exploration.
PMID- 29939350
TI - The effect of Crude Protein Reduction on Performance and Nitrogen Metabolism in
Piglets (four to nine weeks of age) Fed two Dietary Lysine Levels.
AB - Lowering the CP level in piglet diets reduces the risk of post-weaning diarrhea
and N excretion to the environment. The question remains at what point CP becomes
limiting. An experiment was designed with 2 standardized ileal digestible (SID)
Lys levels (10 and 11 g) and 6 CP levels (140, 150, 160, 170, 180, 190 g/kg) in a
2 x 6 factorial design (with 6 pens of 6 animals each per treatment). Linear and
quadratic (QP) mixed models of performance in function of CP were fitted to study
the effect of Lys and CP and their interaction. To determine optima, QP models
and broken line models with linear (BLL) or quadratic (BLQ) ascending portions
were fitted through the data. It was hypothesized 1) that the response to a
decreasing digestible CP level could be described with broken line models and 2)
that the breakpoint of these models is dependent on the dietary SID Lys level.
Decreasing the CP level decreased ADG (P < 0.001). For G:F, the effect of
decreasing CP level depended on the SID Lys level (P of the interaction = 0.028
in the linear model and P = 0.002 in the QP model). According to the BLL model,
with 11 g SID Lys in the diet, G:F started to decline with CP levels below 176 g
CP (SID Lys:apparent total tract digestible (ATTD) CP = 0.077), and with 10 g SID
Lys, CP levels below 165 g/kg (SID Lys:ATTD CP = 0.075) depressed performance.
Serum creatinine levels showed a linear decrease with increasing Lys:CP levels (P
< 0.001). Across both SID Lys levels, when fitting a BLL model, minimal serum
urea levels were reached at a Lys:CP ratio of 0.064. This seems to be the point
where CP and not Lys limits muscle deposition. The small difference in breakpoint
between serum urea level and performance suggests that the composition of
nonessential AA may be also at stake. The effect of decreasing CP level depends
on SID Lys and using a maximal SID Lys:CP ratio may be useful for optimizing the
AA profile of dietary CP. When the Lys:CP ratio exceeds 0.064 (SID Lys:ATTD CP
above 0.079), protein and not individual AA limits growth in most piglets between
4 and 9 weeks of age.
PMID- 29939352
TI - Signatures of microevolutionary processes in phylogenetic patterns.
AB - Phylogenetic trees are representations of evolutionary relationships among
species and contain signatures of the processes responsible for the speciation
events they display. Inferring processes from tree properties, however, is
challenging. To address this problem we analysed a spatially-explicit model of
speciation where genome size and mating range can be controlled. We simulated
parapatric and sympatric (narrow and wide mating range, respectively) radiations
and constructed their phylogenetic trees, computing structural properties such as
tree balance and speed of diversification. We showed that parapatric and
sympatric speciation are well separated by these structural tree properties.
Balanced trees with constant rates of diversification only originate in sympatry
and genome size affected both the balance and the speed of diversification of the
simulated trees. Comparison with empirical data showed that most of the
evolutionary radiations considered to have developed in parapatry or sympatry are
in good agreement with model predictions. Even though additional forces other
than spatial restriction of gene flow, genome size, and genetic
incompatibilities, do play a role in the evolution of species formation, the
microevolutionary processes modeled here capture signatures of the
diversification pattern of evolutionary radiations, regarding the symmetry and
speed of diversification of lineages.
PMID- 29939354
TI - IGF2-derived miR-483-3p contributes to macrosomia through regulating trophoblast
proliferation by targeting RB1CC1.
AB - STUDY QUESTION: What is the role of insulin-like growth factor 2 (IGF2)-derived
miR-483-3p in macrosomia? SUMMARY ANSWER: IGF2-derived intronic miR-483-3p is
overexpressed in macrosomia placentas, and miR-483-3p prompts HTR-8/SVneo
extravillous trophoblast cell line proliferation through down-regulation of its
target RB1 inducible coiled-coil 1 (RB1CC1). WHAT IS KNOWN ALREADY: Macrosomia is
a common pregnancy-associated disease and causes a number of adverse maternal and
perinatal outcomes. The development of macrosomia is reportedly attributable to
over proliferation of the placental cells. MicroRNAs (miRNAs) play an important
role in the development of fetal and placenta by regulating their target genes.
Here, we investigated the role of IGF2-derived intronic miR-483-3p in macrosomia.
STUDY DESIGN, SIZE, DURATION: The expression of IGF2, miR-483-3p and its target
gene in placental tissues from 30 pregnant women who had macrosomia was compared
to those of 30 gestation-matched healthy pregnant controls. For in vitro studies,
the human first trimester extravillous trophoblast cell line, HTR-8/SVneo cell
was used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placenta tissues were
collected from pregnant women who had macrosomia without diabetes or other
complications (n = 30) and healthy pregnant controls (n = 30). HTR-8/SVneo cells
were transfected with specific miRNA mimics or inhibitors. MiRNA and mRNA
isolated from placenta tissues or cells were measured by quantitative real-time
PCR. Protein was measured by western blot. Cell proliferation was assayed using a
colorimetric proliferation assay method. Cell cycle and apoptosis were analyzed
by flow cytometry. The putative targets of miR-483-3p were predicted using the
TargetScan, miRanda, miRDB and DIANA algorithms. Dual luciferase reporter assay
was used to measure the relationship of miR-483-3p and RB1CC1. MAIN RESULTS AND
THE ROLE OF CHANCE: IGF2-derived miR-483-3p was overexpressed in macrosomia
placentas. miR-483-3p promoted proliferation in HTR-8/SVneo cells and had a
positive relationship with its host gene IGF2. Subsequently, RB1CC1 was confirmed
as a direct target of miR-483-3p, which may be an important mediator of cell
growth regulation for miR-483-3p. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR
CAUTION: The level of IGF2 and its intronic miR-483-3p in the serum of these
participants was not investigated. Further studies are required to understand the
mechanisms underlying the cause of the increase of IGF2 and miR-483-3p in
macrosomia. WIDER IMPLICATIONS OF THE FINDINGS: These findings give a new insight
into the role of intronic miRNA and its host gene in the development of
macrosomia. Furthermore, it may offer a new target for prognostic and therapeutic
intervention for macrosomia. STUDY FUNDING/COMPETING INTEREST(S): This work was
supported by awards from National Natural Science Foundation of China (Nos.
81401213, 81673217, 81703260), Jiangsu Provincial Medical Youth Talent (No.
QNRC2016110), Jiangsu Overseas Visiting Scholar Program for University Prominent
Young & Middle-aged Teachers and Presidents, the Priority Academic Program for
the Development of Jiangsu Higher Education Institutions (Public Health and
Preventive Medicine), the Education Department of Jiangsu Province (No.
16KJB330010), the Science and Technology Department of Jiangsu Province (No.
BK20160227), the China Postdoctoral Science Foundation funded project (No.
2016M601892). The authors declare no competing financial interests.
PMID- 29939355
TI - Nephrotoxicity and Renal Pathophysiology: A Contemporary Perspective.
AB - The kidney consists of numerous cell types organized into the nephron, which is
the basic functional unit of the kidney. Any stimuli that induce loss of these
cells can induce kidney damage and renal failure. The cause of renal failure can
be intrinsic or extrinsic. Extrinsic causes include cardiovascular disease,
obesity, diabetes, sepsis, and lung and liver failure. Intrinsic causes include
glomerular nephritis, polycystic kidney disease, renal fibrosis, tubular cell
death, and stones. The kidney plays a prominent role in mediating the toxicity of
numerous drugs, environmental pollutants and natural substances. Drugs known to
be nephrotoxic include several cancer therapeutics, drugs of abuse, antibiotics,
and radiocontrast agents. Environmental pollutants known to target the kidney
include cadmium, mercury, arsenic, lead, trichloroethylene, bromate, brominated
flame retardants, diglycolic acid, and ethylene glycol. Natural nephrotoxicants
include aristolochic acids and mycotoxins such as ochratoxin, fumonisin B1, and
citrinin. There are several common characteristics between mechanisms of renal
failure induced by nephrotoxicants and extrinsic causes. This common ground
exists primarily due to similarities in the molecular mechanisms mediating renal
cell death. This review summarizes the current state of the field of
nephrotoxicity. It emphasizes integrating our understanding of nephrotoxicity
with pathological-induced renal failure. Such approaches are needed to address
major questions in the field, which include the diagnosis, prognosis and
treatment of both acute and chronic renal failure, and the progression of acute
kidney injury to chronic kidney disease.
PMID- 29939353
TI - Mice Lacking the Cytochrome P450 1B1 Gene Are Less Susceptible to Hyperoxic Lung
Injury Than Wild Type.
AB - Supplemental oxygen is a life-saving intervention administered to individuals
suffering from respiratory distress, including adults with acute lung injury
(ALI) and acute respiratory distress syndrome (ARDS). Despite the clinical
benefit, supplemental oxygen can create a hyperoxic environment that increases
reactive oxygen species, oxidative stress, and lung injury. We have previously
shown that cytochrome P450 (CYP)1A enzymes decrease susceptibility to hyperoxia
induced lung injury. In this investigation, we determined the role of CYP1B1 in
hyperoxic lung injury in vivo. Eight- to ten-week old C57BL/6 wild type (WT) and
Cyp1b1-/- mice were exposed to hyperoxia (>95% O2) for 24-72 h or maintained in
room air (21% O2). Lung injury was assessed by histology and lung weight to body
weight (LW/BW) ratios. Extent of inflammation was determined by assessing
pulmonary neutrophil infiltration and cytokine levels. Lipid peroxidation markers
were quantified by gas chromatography mass spectrometry, and oxidative DNA
adducts were quantified by 32P-postlabeling as markers of oxidative stress. We
found that Cyp1b1-/- mice displayed attenuation of lung weight and pulmonary
edema, particularly after 48-72 h of hyperoxia compared with WT controls.
Further, Cyp1b1-/- mice displayed decreased levels of pulmonary oxidative DNA
adducts and pulmonary isofurans after 24 h of hyperoxia. Cyp1b1-/- mice also
showed increased pulmonary CYP1A1 and 1A2 and mRNA expression. In summary, our
results support the hypothesis that Cyp1b1-/- mice display decreased hyperoxic
lung injury than wild type counterparts and that CYP1B1 may act as a pro-oxidant
during hyperoxia exposure, contributing to increases in oxidative DNA damage and
accumulation of lipid hydroperoxides.
PMID- 29939356
TI - Erratum to "High-Throughput H295R Steroidogenesis Assay: Utility as an
Alternative and a Statistical Approach to Characterize Effects on
Steroidogenesis".
PMID- 29939357
TI - Association between long-term exposure to air pollution and sleep disorder in
Chinese children: the Seven Northeastern Cities study.
AB - Study Objectives: There is limited knowledge regarding the effects of air
pollution on sleep disorders, particularly in children. The aim of this study is
to investigate this association in Chinese children. Methods: During 2012-2013,
59754 children aged 2-17 years were randomly selected from 27 districts in seven
northeastern Chinese cities. All participants' sleep was evaluated with the Sleep
Disturbance Scale for Children. Four year average concentrations of pollutants
were calculated for particles with an aerodynamic diameter of <=1 um (PM1), <=2.5
um (PM2.5) from a spatial statistical model, and <=10 um (PM10), sulfur dioxide
(SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO) from
monitoring stations. To examine the effects, two-level regression analysis was
used, controlling for covariates. Results: We observed that sleep disorder was
generally associated with all air pollutants, with the highest odds among PM1
exposure for male (odds ratio [OR] 1.55; 95% confidence interval [95% CI] 1.36
1.76) and female (OR 1.50; 95% CI 1.30-1.72) children. The overall strongest
association with sleep disorder symptom was exposure to PM1 and Disorders of
Excessive Somnolence (OR 1.43; 95% CI 1.30-1.58). PM1 and PM2.5 were strongly
associated with all sleep disorder symptoms in females (ORs ranged for PM1 from
1.19 to 1.49; and PM2.5 1.18 to 1.44). The association between air pollutants and
total sleep score was generally greater in female than in male children.
Conclusions: Our findings suggest that exposure to air pollutants increases the
odds of sleep disorder in children and point to the need to make reducing
exposure to air pollutants a public health priority.
PMID- 29939358
TI - Effect of Pb Exposure on Synaptic Scaling Through Regulation of AMPA Receptor
Surface Trafficking.
AB - Homeostatic synaptic plasticity (HSP) helps to stabilize the neuronal network
activity, which is essential for optimal information coding. Synaptic scaling is
a form of homeostatic plasticity that stabilizes neuronal firing in response to
activity blockade. Lead (Pb) is a ubiquitous environmental neuro-toxicant and can
impair the input-specific Hebbian type synaptic plasticity, but whether Pb exerts
effects in HSP remains unknown. We previously reported that blocking L-type
calcium channel induces synaptic scaling, which stimulates the synthesis of all
trans retinoic acid (RA) and the expression of GluA2-lacking alpha-amino-3
hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Given Pb is a potent
blocker of calcium channel, we hypothesized Pb may participate in synaptic
scaling accompanied by RA synthesis and AMPA receptor trafficking. In this study,
cultured hippocampal neurons were treated with Pb (1 MUM 5 min, 15 min, 4 h, 24
h, and 10 MUM 24 h) alone or in combination with tetrodotoxin (TTX, 1 MUM, 24 h).
The results showed that Pb alone, either at 1 MUM or 10 MUM, cannot induce
synaptic scaling. But Pb participated in synaptic scaling when concurrent with
TTX (10 MUM Pb + 1 MUM TTX, 24 h). Further results showed that surface
heteromeric GluA1 and GluA2 AMPA receptors were increased in TTX+ Pb-induced
synaptic scaling. In addition, RA was proved not to participate in TTX+ Pb
mediated synaptic scaling. Taken together, our work supported that TTX+ Pb could
induce synaptic scaling and enhance synaptic accumulation of AMPAR GluA1 and
GluA2 during synaptic up scaling. Our study would help for elucidation of the Pb
induced neuronal network instability mechanism.
PMID- 29939359
TI - JMCB in the 10th year: call for changes.
PMID- 29939360
TI - Prognostic nutritional index and early mortality with percutaneous endoscopic
gastrostomy.
AB - Background: Although percutaneous endoscopic gastrostomy (PEG) is a well-accepted
and less invasive method of feeding tube placement in patients with swallowing
difficulties, complications and early death after PEG have been reported. Aim:
This study aimed to evaluate predictive factors associated with 30-day mortality
after PEG, and to assess the utility of nutritional supporting period before PEG
in reducing early mortality following PEG. Design: An observational study.
Methods: We retrospectively analyzed 268 patients who underwent PEG at Sapporo
Shirakaba-dai Hospital from 2006 to 2010, using clinical and laboratory data to
analyze predictive factors associated with early death after PEG. Then, we
prospectively assessed 152 consecutive patients assessed for eligibility for PEG
from 2011 to 2014. We assessed the patients' nutritional condition using
Onodera's prognostic nutritional index (PNI), and supported nutrition for more
than 10 days before PEG in patients with a poor nutritional index (PNI < 37).
Results: In both univariate and multivariate analyses in the retrospective study,
Onodera's PNI of less than 37 was the only predictive factor for early mortality.
In the second study, among the 115 patients who finally underwent PEG, early
mortality rates improved to 1.7% from 5.2% in the first study. Conversely, 32% of
patients with malnutrition who did not undergo PEG died within 30 days.
Conclusion: Nutritional status might be a predictive factor for early mortality
after PEG. In patients with poor nutritional status, nutritional supporting
period before PEG might improve the outcomes and reduce unnecessary PEG.
PMID- 29939361
TI - The Multiple Dimensions of Insight in Schizophrenia-Spectrum Disorders.
AB - The concept of insight is used to indicate the propensity of patients with
schizophrenia and other severe mental disorders to recognize their illness and
engage in treatment. Thus, insight may have notable consequences for the ill
individual: Those who lack insight are at higher risk of nonadherence to
treatments, negative clinical outcomes, and worse community functioning. Although
insight is an intuitive concept, its essence remains difficult to capture.
However, many rating scales are available to aid assessment, both for clinical
and research purposes. Insight cannot be reduced to a symptom, a psychological
mechanism, or a neuropsychological function. It is likely to have dynamic
relationships with all these dimensions and with responses to personal events and
contextual factors. In particular, social consequences of mental illness and
explanatory models that are alternative to the medical model may fundamentally
shape insight and treatment choice. Moreover, the cultural or individual
stigmatization of mental illness may turn the acquisition of insight into a
painful event and increase the risk of depression. Clinicians need to carefully
evaluate and promote insight through a personalized approach to aid patient
process of care and personal growth.
PMID- 29939362
TI - Education, education, education-now more than ever?
AB - The generation of scientists and physicians that took part in starting the whole
era of modern-assisted reproduction is currently close to retirement or has
already left research. A new generation is about to take over and the profession
is facing a massive transgenerational transition. Since current treatments have
reached a plateau in success rates and costs, new research and development is
required to further advance the field. Today, multi-disciplinary platforms
including numerous research areas, not previously integrated in our field, are
fundamental to achieve new clinical approaches. Structured, broader and
purposeful education of young researchers should be intensified and prioritized,
and innovative educational initiatives are needed to facilitate 'thinkers' and
advance developments in the field of assisted reproduction.
PMID- 29939363
TI - Effects of Military Service on Marital Stability Among World War II U.S. Veterans
of Japanese Descent.
AB - Introduction: This study had two goals. First, we investigated how World War II
(WW II) military service impacted marital stability during men's young and middle
adulthood in a large community sample of American men of Japanese descent.
Second, within a subgroup of WW II veterans, we assessed how the level of combat
exposure affected marital stability. Material and Methods: The Honolulu Heart
Program and later Honolulu-Asia Aging Project were longitudinal, community-based
studies of Japanese-American men living in Hawai'i. This study is a secondary
data analysis of 1,249 male WW II veterans and 3,489 men of Japanese descent who
were civilians during WW II, born 1910-1919, who completed interviews at the
first (1965-1968) and third (1971-1975) exams. Data from a subsample of veterans
who completed a military service interview during the sixth exam (1997-1999) also
were used. In the first set of analyses, we compared veterans to civilians on
three marital outcomes for ages 15-59: (1) likelihood of never marrying, (2) age
at first marriage, and (3) likelihood of divorce. Next, we investigated the
negative consequences of increasing combat exposure on the same marital outcomes.
All analyses controlled for age in 1941 and occupation. Results: Overall, 88% of
the sample remained in their first marriage with no differences between veterans
and civilians. We found no effects of military service on the timing of first
marriages on the likelihood of divorce during young and middle adulthood.
However, among those who had not married before WW II, veterans were
significantly more likely to remain unmarried compared with civilians; odds ratio
= 1.52 (1.10, 2.09). The level of combat exposure did not predict any of the
three marital outcomes among WW II veterans. In fact, none of the other military
service characteristics assessed (i.e., age of military induction, years of
service, and service-connected disability) predicted marital outcomes. We found
that age at the beginning of WW II impacted the timing and stability of marriage
in both veterans and civilians. Finally, we identified cultural effects on the
likelihood of marriage between Nisei and Kibei groups with Nisei men being less
likely to marry. Conclusion: Similar to other groups in this era, long-term
marriage with one partner was the norm for both veterans and civilians. For a
small portion of American men of Japanese descent, military service seemed to
impact the transition into marriage. However, we found no differences in the
timing of marriage or the likelihood of divorce based on military service or
level of combat exposure. While our findings are inconsistent with previous
research on the impact of military service and combat exposure, much of that
research was conducted with mainland veterans, usually of European descent. There
appears to be little long-term disruption of life course events. Results
highlight the importance of studying diverse groups of veterans to understand how
experiences in the military interact with pre-military factors in defining long
term responses to military service.
PMID- 29939364
TI - Functional limitations in workers with hand-arm vibration syndrome (HAVS).
AB - Background: Hand-arm vibration syndrome (HAVS) is a chronic occupational disease
affecting workers exposed to hand-transmitted vibration. However, limited
information exists on task-related disability experienced by workers with HAVS.
Aims: This study was conducted to characterize the impact of HAVS on task-related
disability and daily life activities. Methods: A retrospective chart review was
undertaken of difficulty in carrying out activities reported by workers with HAVS
who had been assessed in an Occupational Medicine clinic in 2015. Prior to their
clinical assessment, the workers had been asked to complete an open-ended
questionnaire regarding activities they were having difficulty performing in the
domains of personal care, household activities and recreational activities or
hobbies. Results: Data from 107 workers diagnosed with HAVS were obtained through
the retrospective chart review. The activities most affected included: getting
dressed (n = 72), lawn maintenance (n = 61), fishing (including ice fishing) (n =
56), snow removal (n = 36), washing the car (n = 26) and doing the dishes (n =
25). Conclusions: These findings reported in an open-ended fashion by workers
with HAVS provide a better understanding of the impact of HAVS on specific
activities of daily living in comparison to highly structured questionnaires
lacking any open-ended responses. Understanding the implications of HAVS on
activities of daily living will contribute to the provision of patient-centred
care, by enabling health care providers to effectively support HAVS patients,
based on workers' actual experiences of functional limitations.
PMID- 29939366
TI - Beauchamp MK, Lee A, Ward RF, et al. Do exercise interventions improve
participation in life roles in older adults? A systematic review and meta
analysis. Phys Ther. 2017;97:964-974.
PMID- 29939365
TI - Patients First: Toward a Patient-Centered Instrument to Measure Impact of Chronic
Pain.
AB - Background: Numerous instruments are available to measure the impact of chronic
pain, yet most have been developed with little or no patient involvement. This
study seeks to start bridging that gap by determining which health aspects or
attributes (to be included in a future instrument) are considered most important
by people with chronic pain. Objective: The goal of this study was to reveal
which attributes reflecting impact of chronic pain are considered most important
by people with chronic pain and to analyze differences in importance according to
gender, age categories, diagnostic subgroups, and pain intensity categories.
Design: This study used a sequential explanatory mixed-methods design: literature
search, focus group meetings, and online survey. Methods: First, a literature
search was performed to identify the attributes in existing instruments. In 68
instruments meeting inclusion criteria, 155 unique attributes were identified, 85
of which remained after applying the exclusion criteria. Second, 2 focus group
meetings, with 6 and 4 patients, respectively, were held to verify that no
attributes had been missed. Three attributes were subsequently added. Third,
individuals with chronic pain were then sent an online survey through several
patient organizations. Results: A total of 939 patients were asked to select the
8 attributes they deemed most important, which resulted in the following list:
fatigue, social life, cramped muscles, sleeping, housekeeping, concentration, not
being understood, and control over pain. The importance assigned to these 8
attributes varied slightly according to age, gender, and diagnostic subgroup.
Limitations: Participation rate could not be established because of the online
survey. Conclusions: Attributes reflecting impact of chronic pain deemed most
important by patients are revealed. Importance of impact differs according to
subgroups. The "patients-first" methodology used here revealed attributes that
were not comprehensively covered in currently available instruments for measuring
the impact of chronic pain.
PMID- 29939368
TI - Bronchogenic cyst.
PMID- 29939367
TI - Efficacy of PRIME, a Mobile App Intervention Designed to Improve Motivation in
Young People With Schizophrenia.
AB - The onset of schizophrenia occurs during a period critical for development of
social relationships and functional independence. As such, interventions that
target the early course of illness have the potential to stave off functional
decline and restore functioning to pre-illness levels. In this entirely remote
study, people with recent-onset schizophrenia spectrum disorders (SSDs)
participated in a 12-week randomized controlled trial to determine the efficacy
of PRIME (personalized real-time intervention for motivational enhancement), a
mobile-based digital health intervention designed to improve motivation and
quality of life. Participants were randomized into the PRIME (n = 22) or
treatment-as-usual/waitlist (TAU/WL) condition (n = 21) and completed assessments
at baseline, post-trial (12 wk), and for people in the PRIME condition, 3 months
after the end of the trial. After 12-weeks, WL participants received PRIME,
resulting in a total sample of 38 participants completing PRIME. In PRIME,
participants worked towards self-identified goals with the support of a virtual
community of age-matched peers with schizophrenia-spectrum disorders as well as
motivation coaches. Compared to the WL condition, people in the PRIME condition
had significantly greater improvements in self-reported depression, defeatist
beliefs, self-efficacy, and a trend towards motivation/pleasure negative symptoms
post-trial, and these improvements were maintained 3 months after the end of
trial. We also found that people in the PRIME condition had significantly greater
improvements in components of social motivation post-trial (anticipated pleasure
and effort expenditure). Our results suggest that PRIME has the potential to be
an effective mobile-based intervention for improving aspects of mood and
motivation in young people with SSDs.
PMID- 29939369
TI - 'J' waves and hypothermia.
PMID- 29939370
TI - Sulfur nutrition stimulates lead accumulation and alleviates its toxicity in
Populus deltoides.
AB - Sulfur (S) can modulate plant responses to toxic heavy metals, but the underlying
physiological and transcriptional regulation mechanisms remain largely unknown.
To investigate the effects of S supply on lead (Pb)-induced toxicity in poplars,
Populus deltoides monilifera (Aiton) Eckenw. saplings were exposed to 0 or 50 MUM
Pb together with one of the three S concentrations (0 (low S), 100 (moderate S)
or 1500 (high S) MUM Na2SO4). Populus deltoides roots absorbed Pb and it was
partially translocated to the aerial organs, thereby decreasing the CO2
assimilation rate and leaf growth. Lead accumulation in poplars caused the
overproduction of O2- and H2O2 to induce higher levels of total thiols (T-SH) and
glutathione (GSH). Lead uptake by the roots and its accumulation in the aerial
organs were repressed by low S application, but stimulated by high S supply. Lead
induced O2- and H2O2 production were exacerbated by S limitation, but alleviated
by high S supply. Moreover, the concentrations of S-containing antioxidants
including T-SH and GSH were reduced in S-deficient poplars, but increased in high
S-treated plants, which corresponded well to the changes in the activities of
enzymes involved in S assimilation and GSH biosynthesis. The transcript levels of
both genes encoding sulfate transporters, i.e., SULTR1.1 and SULTR2.2, were
elevated by low S application or high S supply in the roots, and the
transcriptional upregulation of both genes was more pronounced under Pb exposure.
Furthermore, the mRNA levels of several genes involved in S assimilation and the
biosynthesis of GSH and phytochelatins, i.e., ATPS1, ATPS3, GSHS1, GSHS2 and
PCS1, were upregulated in poplar roots with high S supply, particularly under Pb
exposure. These results indicate that a high S supply can stimulate Pb
accumulation and reduce its toxicity in poplars by improving S assimilation and
stimulating the biosynthesis of S-containing compounds including T-SH and GSH.
PMID- 29939371
TI - The Ben Pimlott Memorial Lecture 2017: The Geopolitical Is Personal: India,
Britain, and American Foreign Correspondents in the 1930s and 1940s.
AB - This lecture explores the shared terrain between the new international history
and the history of emotions. In the summer and fall of 1942, American foreign
correspondents played a key role in sparking a furore over British rule in India.
Drawing on their own first-hand reporting from India, they depicted the British
Empire as retrograde and abusive, a dangerous, destabilizing force and a threat
to the post-war peace. Diagnosing what it called 'a new landslide of anti-British
feeling', the British Ministry of Information spearheaded the formation of high
level, interdepartmental, secret committee charged with the task of figuring out
how to reconcile Americans to the British Empire. What they found was that the
job itself was impossible: a significant proportion of Americans 'whose views,
they concluded, were driven in large measure by emotion' would not under any
circumstances soften their opinions about the British Empire.
PMID- 29939373
TI - The Prairie Home Companion Approach to Beginning and Ending a Manuscript.
PMID- 29939372
TI - Cadmium Activates Noncanonical Wnt Signaling to Impair Hematopoietic Stem Cell
Function in Mice.
AB - Cadmium (Cd) is a toxic heavy metal that impairs the development of hematopoietic
stem cells (HSCs) in mice, yet the mechanism of how Cd influences HSC remains
elusive. Herein, we show that Cd activated non-canonical Wnt signaling pathway to
impair HSC function in mice. After exposure to 10 ppm Cd chloride (CdCl2) via
drinking water for 3 months, C57BL/6 mice displayed aberrant HSC function, in
that HSC from Cd-treated mice were less efficient in rescue of lethally
irradiated hosts and less competitive under mixed chimeric condition. Further
analyses indicated that the small GTPase cdc42 was activated and its distribution
pattern was depolarized in HSC by Cd exposure, and inhibition of cdc42 by casin,
a selective chemical inhibitor, recovered the HSC capacity in rescue assay and
their potential for lymphopoiesis under competitive mixed chimeric assay. Cd
interaction with HSC was sufficient to promote noncanonical Wnt signaling
pathway, but not canonical Wnt signaling pathway, to drive cdc42 activation and
further increase the expression of C/EBPalpha and decrease the expression of
Hhex. Moreover, Cd-induced activation of non-canonical Wnt signaling pathway in
HSC did not persist long-termly in the presence of a normal niche without Cd, in
that the elevated non-canonical Wnt signaling by Cd was diminished in HSC in the
BM of normal recipients receiving purified HSC from Cd-treated mice after 6
months posttransplantation. Taken together, our study suggests that Cd activates
cdc42 of noncanonical Wnt signaling pathway to impair HSC function, a previously
unknown mechanism for Cd toxicity on HSC.
PMID- 29939374
TI - An Update on Kirkpatrick's Model of Evaluation: Part Two.
AB - Since Kirkpatrick first published his evaluation model, many continuing nursing
education providers have used it. The model has stood the test of time. In 2016,
the model was updated by Kirkpatrick's son and daughter-in-law through the
addition of five simple principles that can serve as a blueprint to maximize
stakeholders and organizational investments, while validating the value of
provider units. J Contin Educ Nurs. 2018;49(7):292-293.
PMID- 29939375
TI - Practical Tips for Facilitating Research in Clinical Nursing Practice.
AB - Nursing research improves patient care, and clinical nurses have unique
leadership perspectives regarding patient care and institutional needs. Clinical
nurses involved in research are curious, are innovative, and implement the best
practices. Many clinical nurses report lack of understanding of the research
process, time, and institutional support as barriers to their involvement in
research. This article presents practical strategies to encourage clinical nurses
to develop and use research skills. J Contin Educ Nurs. 2018;49(7):294-296.
PMID- 29939376
TI - Creating Interprofessional Teams.
AB - In an era where collaboration is integral to effective care of patients and
families, staff development educators can have a powerful effect on
interprofessional team development. This first article in a five-part Teaching
Tips series emphasizes the work of creating competencies for such teams. It is
neither effective nor advisable to create a group of people and tell them to go
be a team. Knowledge, skills, and tools are helpful in creating such teams, which
will be a focus of these next several Teaching Tips articles. J Contin Nurs Educ.
2018;49(7):297-298.
PMID- 29939377
TI - A Qualitative Description of Nurses' Experiences With Incorporating Research Into
Practice.
AB - BACKGROUND: Baccalaureate-prepared nurses should be competent in accessing,
evaluating, and implementing research evidence into nursing practice. The purpose
of this study was to gain insight into nurses' experiences in accessing,
evaluating, and implementing research into practice. METHOD: Researchers
conducted a qualitative descriptive study. Data were collected through in-depth
interviews and field notes. RESULTS: Thirteen nurses participated in individual
interviews. Themes that emerged included awareness, motivation-empowering change,
and barriers to evidence-based practice implementation (EBP). Several experienced
nurses expressed the importance of EBP in practice but could not provide clear
definitions of EBP. Personal and organizational barriers negatively influence EBP
implementation in clinical practice. Nurses could be motivated to use EBP if it
were translated in an easy way to understand. CONCLUSION: The information derived
from this study can be used to design learning opportunities that prepare
practicing nurses to appropriately appraise research and integrate evidence into
practice. J Contin Educ Nurs. 2018;49(7):299-306.
PMID- 29939378
TI - "I Am Surprised at the Change in Me": What Is It Like for Nurses to Be in the
Process of Completing a Baccalaureate Degree in Nursing?
AB - BACKGROUND: The percentage of nurses with a baccalaureate degree in nursing (BSN)
affects patient morbidity and mortality, so health care organizations are
encouraging staff nurses to finish their BSN degree. However, there is little
data related to what it is like for RNs to return to school. METHOD: In this
qualitative, descriptive study, 16 RN-to-BSN students were interviewed using
naturalistic inquiry processes to gain an understanding of what it is like for
students in the midst of an RN-to-BSN program. RESULTS: Students encountered
financial and work-life barriers to seeking BSN completion yet found it to be
worth the effort. Indeed, they are "surprised at the change in" themselves.
CONCLUSION: Support that could benefit RN-to-BSN students is detailed, including
from employers (e.g., flexible scheduling), faculty (e.g., rapid feedback and
grading), and students themselves (e.g., understand personal time constraints).
More research is needed to determine the priorities of support that facilitates
RN-to-BSN students. J Contin Educ Nurs. 2018;49(7):307-314.
PMID- 29939379
TI - An Educational Intervention to Evaluate Nurses' Knowledge of Heart Failure.
AB - BACKGROUND: Nurses are the main providers of patient education in inpatient and
outpatient settings. Unfortunately, nurses may lack knowledge of chronic medical
conditions, such as heart failure. METHOD: The purpose of this one-group pretest
posttest intervention was to determine the effectiveness of teaching intervention
on nurses' knowledge of heart failure self-care principles in an ambulatory care
setting. The sample consisted of 40 staff nurses in ambulatory care. Nurse
participants received a focused education intervention based on knowledge
deficits revealed in the pretest and were then resurveyed within 30 days. Nurses
were evaluated using the valid and reliable 20-item Nurses Knowledge of Heart
Failure Education Principles Survey tool. RESULTS: The results of this project
demonstrated that an education intervention on heart failure self-care principles
improved nurses' knowledge of heart failure in an ambulatory care setting, which
was statistically significant (p < .05). CONCLUSION: Results suggest that a
teaching intervention could improve knowledge of heart failure, which could lead
to better patient education and could reduce patient readmission for heart
failure. J Contin Educ Nurs. 2018;49(7):315-321.
PMID- 29939380
TI - Rural Mentorships in Health Care: Factors Influencing Their Development and
Sustainability.
AB - BACKGROUND: The need to recruit and retain health care providers remains a
concern in rural communities. This project aimed to better understand what health
care providers and senior leaders value in mentorship and determine the best way
to implement a mentorship program in rural western Canada. METHOD: Health care
providers and senior leaders from a rural health region were recruited through
convenience and snowball sampling. Participants were interviewed using a
semistructured interview guide, and data were analyzed using thematic analysis.
RESULTS: Two main themes were revealed: rural mentorship challenges and
facilitators. Challenges included administrative, scope of practice, and
interpersonal, whereas facilitators included mentorship as a recruitment and
retention strategy, openness and commitment, structured mentorship programs, and
community influence. CONCLUSION: This information will enable administrators and
educators to more successfully implement mentorship programs for a variety of
health care professionals working within rural environments and facilitate staff
development, recruitment, and retention. J Contin Educ Nurs. 2018;49(7):322-328.
PMID- 29939382
TI - Erratum for "Global Health Nursing: Making Connections by Embracing the Other".
PMID- 29939381
TI - Benefits of Health Care Communication Training for Nurses Conducting Bedside
Handovers: An Australian Hospital Case Study.
AB - BACKGROUND: This study aimed to examine the effects of communication training on
nurses' ability to conduct bedside handovers in hospital. METHOD: Of the 26
participating nurses, 13 had recently completed specialized training in bedside
handovers using the Connect, Ask, Respond, and Empathize (CARE) and Past,
Present, and Future (PPF) of the patient journey and condition protocols for
health care communication. The other 13 nurses did not participate in this
training. Researchers videotaped and evaluated these nurses' handover practices
using the Bedside Handover Evaluation Form. RESULTS: Nurses who had received the
specific training in bedside handovers interacted with their patients to a far
greater extent, asked more questions, and stated more complete information about
their patient's medical journey. CONCLUSION: Nurses who participate in health
care communication training on bedside handovers subsequently demonstrate a
significantly better ability to lead these clinical interactions. This is
evidenced by their articulation of more detailed medical information, their more
respectful and multifaceted interactions with patients, and their more inclusive
approach to all participants in the handover. J Contin Educ Nurs. 2018;49(7):329
336.
PMID- 29939384
TI - Analysing the effects of working period on psychophysiological states of
seafarers.
AB - BACKGROUND: Human factor has become a critical issue due to the fact that all
operational processes in maritime transportation have been accelerated with
technological innovations. Irregular and long working hours, rapid change of
working environments and other organisational and/or individual factors have
negative impact on the performance of the seafarers as well as other
transportation workers and/or shift workers. Seafarers working under the
influence of these stressor factors, naturally, are affected from
psychophysiological and cognitive aspects, which in return decrease their overall
performances. The study mainly aimed to investigate which of the above mentioned
affecting factors had greater impact on seafarers' performances. MATERIALS AND
METHODS: For this purpose, data for 14 healthy male seafarers on board different
vessels was collected. The collected data included the number of port visits,
frequency of change of circadian rhythm, total working hours and watchkeeping
periods in the recent month. In order to analyse the psychophysiological effect
of working period, electrodermal activity and heart rate variability measurements
for arousal mood and data from 2-choice reaction time tests for cognitive
performance were collected from the seafarers. RESULTS: Obtained data was
analysed in SPSS software programme applying multiple regression with factor
analysis to model the dependence between psychophysiological states of seafarers
and working periods. CONCLUSIONS: According to the results, it was determined
that the change of circadian rhythm is the main determinant factor for seafarers.
The results showed that when seafarer's circadian rhythm is changed more
frequently, they experience more drowsiness.
PMID- 29939383
TI - Cruise ship pathologies in remote regions.
AB - BACKGROUND: Navigations on cruise ships are rising and tend to spread to remote
areas like polar regions. Our aim was to assess the prevalence of pathologies
encountered on a cruise ship navigating in remote areas including Polar Seas.
MATERIALS AND METHODS: A prospective observational, descriptive and cross
sectional study was conducted aboard a cruise ship with an overall capacity of
200-264 passengers and 140 crewmembers, sailing in remote areas as the Arctic
Ocean and the Antarctic Peninsula over a period of 205 days. The database was
built on all first consultations for passengers and crewmembers done by the
onboard physician. Each symptom and diagnosis was coded according to the
"International Classification of Primary Care, 2nd edition". For statistical
analysis, the quantitative data were expressed as mean +/- standard deviation and
qualitative data as percentages. The percentages were compared using a c2 test
corrected according to the Yates' method or by a Fisher test when appropriate.
RESULTS: A total of 446 diagnoses were studied on the 910 consultations
originally included (13.7% of the people on board). The median age for the
passengers and the crewmembers was respectively 68 (age ranging from 12 to 90)
years and 31 (18-62) years. Likewise, the sex ratio (male/female) was 0.98 and
3.23. Infectious diseases were predominant (prevalence of 43.7%). Among them,
respiratory infections were the most common and gastroenteritis seemed to be more
frequent in passengers (prevalence of 11.5% vs. 5%, p = 0.10). Cutaneous
pathologies were more frequent in crewmembers (prevalence of 26.6% vs. 18.7%, p =
0.04) and allergic dermatitis was the second most frequent in this group of
patients (prevalence of 7.2%). Cardiovascular diseases, more common in passengers
(p = 0.05), represented 4% of all diagnoses. Two cases of phlebitis, one stroke
and one subacute heart failure were diagnosed. Among traumatic injuries,
cutaneous traumas were the commonest (prevalence of 76.5%). Musculoskeletal
traumas were more common in passengers (p = 0.04). An acute gastrointestinal
haemorrhage required a medical evacuation from the Antarctic Peninsula.
CONCLUSIONS: The physician should be prepared to face emergency cases by
developing personal expertise specific to maritime medicine in remote areas.
Highlighting the particularity of cases handled in remote areas, our results
should also pave the way of the development of medical protocols for ships
lacking physician.
PMID- 29939385
TI - Violations of safe diving practices among 122 diver fatalities.
AB - BACKGROUND: Diving is a popular recreation with an excellent safety record, with
an estimated 1.8 deaths per 1 million dives. This study investigated the
relationship between intentional deviation from accepted diving practices
(violations) and diver fatalities. MATERIALS AND METHODS: The authors examined
119 incidents/122 diver fatalities that did not involve diver training in North
America and the Caribbean, and identified the presence of violations of accepted
diving safety practices, as well as if the death was associated with an acute
medical event such as heart attack. RESULTS: Of the 122 fatalities, 57% (n = 70)
were associated with a medical event and 43% (n = 52) were non-medical.
Violations were found in 45% of fatalities (n = 55) overall. Violations were
recorded for 23% of the 70 medical and 75% of the 52 non-medical fatalities.
Divers who died from something other than a medical cause were 7 times as likely
to have one or more violations associated with the fatality (OR 7.3, 95% CI 2.3
23.2). The odds of dying from something other than a medical condition increased
approximately 60% for each additional 10 metres of depth. The odds of a death
being associated with a medical condition increased approximately 9% per year of
age, or 2.4 times for every 10 years older a diver was. CONCLUSIONS: Medical
events are associated with over half of the non-training related diver fatalities
in North America and the Caribbean, with the odds of death being associated with
a medical condition doubling each decade of additional age. These data support
recommendations that divers stay physically fit and have regular medical
checkups, particularly as they get older. They also strongly support the safety
benefit of adhering to established safe diving practices.
PMID- 29939386
TI - Causes and circumstances of maritime casualties and crew fatalities in British
merchant shipping since 1925.
AB - BACKGROUND: To determine the causes and circumstances of vessel accidents that
led to fatalities in British merchant shipping since 1925, and among British
seafarers who were employed in non-United Kingdom shipping since 1985. Secondly,
to establish trends in vessel accidents and crew fatalities, and associations
with type of casualty and location, type of ship, cargo carried and season.
MATERIALS AND METHODS: Reviews of annual mortality returns, marine accident
investigation reports, death inquiry files, Lloyd's casualty returns, online
newspapers, shipwreck websites and other searches over the period from 1925 to
2017 but excluding 1939 to 1946. RESULTS: The study identified 362 ship accidents
in British shipping that led to 2760 crew and 605 passenger fatalities. There
have been large reductions in both ship casualty and crew fatality rates, which
have been greatest for vessels that were stranded, wrecked or foundered,
particularly small coastal trading cargo ships. Reductions since the 1980s have
coincided with proportionate increases in ship accidents and consequential crew
fatalities among British seafarers employed in 'open register' shipping. Strong
seasonal and geographical patterns show that most fatalities through foundering
or wrecking occurred during winter months around Europe. CONCLUSIONS: Reductions
in ship accidents and crew fatalities reflect major developments and improvements
in ship navigational aids, improvements in rescue services and ship designs, and
reductions in the volume of small coastal trading ships. Some disasters in 'open
registry' shipping occurred in controversial circumstances, suggesting that
substandard shipping has been flagged out or that lower cost but less competent
crews have been employed.
PMID- 29939387
TI - Occupational safety and health in maritime sector in Morocco 60 years after
independence: current state, constraints and prospects.
AB - BACKGROUND: The aim of this study was to evaluate the situation 60 years after
independence, to assess the current state, to highlight the constraints and to
propose recommendations for improving occupational health in the maritime sector.
MATERIALS AND METHODS: This study was based on collecting data of: 1) Legislative
texts on occupational health and safety; 2) Statistics from administrations
(Ministry of Health and Ministry of Marine Fisheries), general medical council of
Morocco, scientific societies and associations of occupational health and
maritime medicine; 3) Analysis of a self-questionnaire sent to 22 physicians
working in fishermen's health services and listed in the yearbook 2017 of the
Moroccan Society of Maritime Medicine. It included five sections: socio
demographic and professional characteristics, training, assessment of activities,
constraints in their exercise and ten priority recommendations to improve the
situation. RESULTS: Health and safety in maritime sector are progressing since
the Labour Code of 2004 and the Convention of December 27, 1996 between the
Ministry of Health and the Ministry of Marine Fisheries. It concerns the
organisation of a fishermen's health prevention with the establishment of the
fishermen's health office at central level and fishermen's health services at the
main ports. However, medical coverage is still insufficient. Maritime medicine
remains an unattractive specialty because the physicians are a poorly paid and
have some difficult working conditions. CONCLUSIONS: The absence of up-to-date
synthetic data on safety and health in maritime sectors led us to carry out this
study, which showed some dysfunctions and deficiencies that hinder the promotion
of workers' health in this sector. The recommendations proposed by the physicians
should be the backbone of any improvement related to occupational health and
safety. It is the practitioners themselves who, faced with their practice, are
the best able to disseminate a reflection qualified as ethical, which cannot be
dissociated from their everyday activities.
PMID- 29939388
TI - Prevalence of consumption of psychoactive substances amongst dockers.
AB - BACKGROUND: Dockers in the port facilities are exposed to significant
psychosocial risks (stress, suffering at work, etc.) related to heavy
organisational, environmental, physical, chemical constraints, etc. These workers
are particularly affected by the consumption of psychoactive substances because
of the dangerousness and complexity of their work. To what extent can these
numerous occupational risks be at the origin of behaviour favouring the
consumption of psychoactive substances? However, in our country no study has
investigated toxic habits in this population. The aim of this study was to
determine the prevalence of the use and misuse of psychoactive substances amongst
dockers, and to appreciate the poly-consumption according to socio-demographic
and occupational characteristics. MATERIALS AND METHODS: This cross-sectional
study was conducted amongst 665 dockers. The interview took place at the
occupational health service and lasted between 15 and 20 minutes for each person
respecting the confidentiality. The questionnaire covered socio-demographic
characteristics, socio-professional characteristics, and toxic habits (tobacco,
alcohol, cannabis and others psychotropic substances). The misuse was assessed by
specific tests: Fagerstrom test for tobacco smoking, Cannabis Abuse Screening
Test (CAST) and Alcohol Use Disorders Identification Test (AUDIT). RESULTS: The
prevalence of use was 30.5% for tobacco smoking, 9.1% for cannabis smoking, and
16.5% for alcohol consumption. The prevalence of toxic habits was significantly
higher in handlers than in machinery operators: tobacco smoking (39.7% vs. 27%; p
= 0.002), snuff tobacco (12.5% vs. 4.6%; p = 0.001), hookah (7.6% vs. 2%; p =
0.001), cannabis smoking (20.6% vs. 4.5%; p = 0.001) and alcohol consumption
(22.3% vs. 14.3%; p = 0.019). Amongst consumers, the prevalence of dependence or
misuse was 45.3% for tobacco smoking, 56.7% for cannabis smoking and 44.5% for
alcohol consumption. Fifty-two point five per cent had no toxic habit, 36.7% had
one toxic habit, 9.9% two toxic habits, and 0.9% three toxic habits. The most
frequent associations were tobacco-alcohol (6.5%), and tobacco-cannabis (3%).
CONCLUSIONS: Occupational health professionals have to play a key role in raising
awareness and fighting against consumption of psychoactive substances amongst
dockers.
PMID- 29939389
TI - Management of a polytrauma in the maritime environment.
AB - BACKGROUND: A polytraumatised person is a severely injured patient with an
association of several injuries including at least one life-threatening. In an
isolated and hostile environment like the maritime environment, the principles of
early care and fast evacuation of a polytraumatised person are sometimes
difficult to apply. CLINICAL CASE: We report the story of a patient with a
bilateral fracture of the lower extremities following an accident on board a
Moldavian tugboat off the coasts of Djibouti. He received a medical treatment
thanks to the intervention of a French military frigate after receiving a message
of assistance by very high frequency, and then a helicopter evacuation to the
Medicine and Surgery "Bouffard" Hospital. The pre-hospital care of a
polytraumatised patients with limb injuries and the specificities of an
intervention in a maritime environment are described. The maritime international
conventions relating to rescue at sea as well as the specificities of the
management of an injured person on a ship sailing under the Moldavian flag are
explained. Emphasis is placed on the importance of watchkeeping at sea and the
presence on board of trained first-aid personnel. Finally, a point is made on the
French organisation of health support for ships, through the Maritime Medical
Consultation Centre and the Regional Operational Centres for Surveillance and
Rescue. CONCLUSIONS: This case illustrates that the solidarity of the seafarers
allows a seriously wounded person to maintain, despite a degraded and isolated
situation, the chances of successful management and preserve the functional
prognosis.
PMID- 29939390
TI - Training needs among maritime professionals: a cross sectional study.
AB - BACKGROUND: Maritime medical practice includes assessment of fitness, management
of medical emergencies and healthcare on board and ashore. A better response to
seagoing professionals' health requirements can be achieved when all the
respective stakeholders have a common understanding. Training is a powerful tool
to raise awareness and in particular continuing professional development is very
significant in sustaining competencies of these professionals. The objective of
the study was to identify maritime professionals' perceived training needs.
MATERIALS AND METHODS: A cross-sectional study was conducted among maritime
professionals participated in the 14th International Symposium on Maritime
Health. Fifty responses with the response rate of 42.7% were received with
medical doctors representing 78% of the sample. Descriptive statistics were used
to describe the basic characteristics of the data needs using STATA 15.1.
RESULTS: Among the 23 themes, the ranking of perceived training needs was highest
for fitness evaluation and examination guidelines and working conditions (both
with the same percentage 86%), onboard medicine 82%, rules and regulations and
health and safety at work (with the same percentage 80%). The lowest was on
gender issues 32%. CONCLUSIONS: The finding suggests the planning and effective
implementation of further training for the maritime health professionals in a
variety of topics including financing and management issues. Highest importance
of training was expressed by those over 40 years and by medical doctors with more
than 10 years of practice. These findings could usefully be combined with a
qualitative study to gain in-depth results and may help the respective
authorities to organise relevant training.
PMID- 29939391
TI - Hepatitis E virus seroprevalence in Polish soldiers serving in harsh
environmental conditions.
AB - BACKGROUND: Hepatitis E virus (HEV) is an under-recognised aetiological factor of
viral hepatitis; it is most commonly transmitted via the oral-faecal route, but
can also be transmitted by blood or blood products, vertically from an infected
mother to the foetus or by transplanted organs. The aim of the study was to
present the current seroprevalence of HEV among soldiers from the Polish Special
Forces deployed on military operations carried out in harsh environmental
conditions. MATERIALS AND METHODS: The research conducted between October and
November 2016 involved 253 active duty soldiers, 237 men and 16 women, aged 26
57, without clinical symptoms of infection, participants in military operations
in Asia and Africa. Accurate HEV diagnosis required the implementation of a two
phase diagnostic protocol. During the first phase, immunoenzymatic ELISA method
was used to detect specific anti-HEV antibodies (IgM and IgG) in blood serum
samples indicating contact with an infectious agent in the past. During the
second phase, serum samples obtained from subjects with positive or inconclusive
test results were tested again using confirmatory recomLine HEV IgM/IgG
immunoassay. RESULTS: Immunoenzymatic assay found anti-HEV antibodies (IgM and/or
IgG) in blood serum samples obtained from 18 soldiers. Confirmatory tests were
carried out among soldiers tested positive with ELISA or those with inconclusive
test results; the confirmatory tests showed anti-HEV antibodies (IgM and/or IgG)
in 16 of the studied soldiers, i.e. 6.3% of the study group. CONCLUSIONS: The
occurrence of HEV infections in Polish soldiers justifies the need for the
introduction of screening tests for HEV in the military environment, especially
among blood donors and in cases of whole blood or blood products transfusion.
PMID- 29939392
TI - Awareness of health risks and communicable diseases among undergraduate maritime
students.
AB - BACKGROUND: In case of an emergency related to crew's health the first
responsible person on board is the appointed officer of the ship. Sometimes these
officers aren't just the only responsible person but also the only available
option. Therefore, they are expected to handle various types of cases from
disease outbreaks to food poisoning. However, officers on board aren't
particularly trained or prepared for such extreme circumstances. Services like
Telemedical Assistances may provide great help in such moments, but the first
identification and contamination of various diseases might not be possible
without previously acquired knowledge and awareness. This study aims to examine
and discover the basic health knowledge and risk awareness of undergraduate
maritime students and assess the needs for improved health training for future
maritime officers. MATERIALS AND METHODS: The study was conducted by proposing an
anonymous questionnaire to the undergraduate students of maritime faculties
located in Turkey. Questionnaire form was adapted from the study of Grappasonni
et al. This questionnaire examines the awareness of health risks and risks of
contracting communicable diseases among seafarers. A total of 266 Turkish
participants joined the study. RESULTS: Basic health knowledge of the maritime
students seems to be well acquired expect for the communicable diseases and food
hygiene. General risk perception for most health issues especially for the
communicable diseases is low for all participants. Findings note that most
maritime students get their health and disease information from Internet sources.
Several differences between Marine Transportation Engineering and Marine
Engineering students are found, related to concerns they feel on board for health
issues. All maritime students are more concerned about the risks of psychological
problems due to isolation. A risk, perception and in some cases awareness shift
is observed between classes. All results are limited with participants'
nationality. CONCLUSIONS: Seafarers should be educated and trained according the
conditions they face on board. An improved training method should be adopted.
This way, the future officers will be qualified to intervene in emergency
situations.
PMID- 29939393
TI - Chikungunya virus infection, immunosuppression and respiratory tract infections:
are they associated?
PMID- 29939394
TI - Managing medical emergencies: risks and responses.
PMID- 29939395
TI - Good neighbors make good defenses: associational refuges reduce defense
investment in African savanna plants.
AB - Intraspecific variation in plant defense phenotype is common and has wide-ranging
ecological consequences. Yet prevailing theories of plant defense allocation,
which primarily account for interspecific differences in defense phenotype, often
fail to predict intraspecific patterns. Furthermore, although individual
variation in defense phenotype is often attributed to ecological interactions,
few general mechanisms have been proposed to explain the ubiquity of variable
defense phenotype within species. Here, we show experimentally that associational
refuges and induced resistance interact to create predictable intraspecific
variation in defense phenotype in African savanna plants. Physically defended
species from four families (Acanthaceae, Asparagaceae, Cactaceae, and Solanaceae)
growing in close association with spinescent Acacia trees had 39-78% fewer spines
and thorns than did isolated conspecifics. For a subset of these species, we used
a series of manipulative experiments to show that this variability is maintained
primarily by a reduction in induced responses among individuals that seldom
experience mammalian herbivory, whether due to association with Acacia trees or
to experimental herbivore exclusion. Unassociated plants incurred 4- to 16-fold
more browsing damage than did associated individuals and increased spine density
by 16-38% within one month following simulated browsing. In contrast,
experimental clipping induced no net change in spine density among plants growing
beneath Acacia canopies or inside long-term herbivore exclosures. Associated and
unassociated individuals produced similar numbers of flowers and seeds, but
seedling recruitment and survival were vastly greater in refuge habitats,
suggesting a net fitness benefit of association. We conclude that plant-plant
associations consistently decrease defense investment in this system by reducing
both the frequency of herbivory and the intensity of induced responses, and that
inducible responses enable plants to capitalize on such associations in
heterogeneous environments. Given the prevalence of associational and induced
defenses in plant communities worldwide, our results suggest a potentially
general mechanism by which biotic interactions might predictably shape
intraspecific variation in plant defense phenotype.
PMID- 29939396
TI - Practitioner Review: Therapeutics of unipolar major depressions in adolescents.
AB - BACKGROUND: Over the past two decades new and key randomized controlled trials
have reported the efficacy, clinical and cost effectiveness of psychological and
pharmacological treatments for adolescents with major depression. METHODS: The
literature was searched through pubmed, psychinfo, scopus and web of science for
randomized controlled trials of current major depression together with meta
analyses and systematic reviews of trials between 2000 and 2017. Those specific
to the adolescent years (11-18 years) were taken as the primary source for this
narrative review. Additional selected studies in adults were used to illustrate
methodological issues. RESULTS: Manualized psychological therapies and the SSRI
fluoxetine are more effective than active placebo in the treatment of major
depressions. Mild to moderate illnesses attending community-based services are
likely to benefit from psychological treatment alone. Moderately to severely ill
patients attending clinic and hospital services are likely to benefit from
monotherapies or combining psychological and pharmacological treatment.
Antidepressants carry a small but significant side-effect risk including
increased suicidality. Side effects from psychotherapies are somewhat lower but
specific negative consequences remain less well characterized. There is some
evidence that CBT-based approaches prevent onset of major depression episode in
well adolescents at high-risk. Other psychological interventions have not been
adequately studied. There has been only limited identification of treatment
moderators and no clear understanding of therapeutic mechanisms. CONCLUSIONS:
There is now a range of clinically effective treatments for depressed
adolescents. Future research needs to reveal moderators of and mechanisms for
individual differences to treatment response, determine psychotherapies of value
for milder depressions, enhance our understanding of safety and side-effects for
all treatments, and consider how to reduce and treat treatment-resistant cases.
PMID- 29939398
TI - Ulcerative epidermal lesions in a koi fish.
PMID- 29939397
TI - Systematic review of prostaglandin analogues for retained placenta.
AB - BACKGROUND: Medical management of retained placenta could be a safe alternative
to manual removal. OBJECTIVE: To evaluate the efficacy of prostaglandin analogues
for retained placenta. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, ICTRP, LILACS,
and OpenSIGLE were searched without language restrictions from inception to
January 31, 2017, by combining terms for retained placenta and prostaglandin
analogues. SELECTION CRITERIA: Randomized controlled trials comparing
prostaglandin analogues with any other intervention. DATA COLLECTION AND
ANALYSIS: Trials were independently assessed for inclusion, data extraction, and
risk of bias. Data were extracted for meta-analyses. GRADE was used to evaluate
the quality of data. MAIN RESULTS: Seven randomized controlled trials (851
patients) were included. Prostaglandins did not increase the placenta expulsion
rate (relative risk [RR] 1.40, 95% confidence interval [CI] 0.83-2.36) or
decrease maternal transfusion (RR 0.72, 95% CI 0.43-1.22). In comparison with
oxytocin, prostaglandins did not modify the expulsion rate (RR 1.26, 95% CI 0.90
1.78), maternal transfusion (RR 1.05, 95% CI 0.27-4.09), or time for delivery of
placenta (mean difference -1.56 minutes, 95% CI, -9.25-6.13). Three trials
comparing prostaglandins with oxytocin agonists, ergometrine, and manual removal
reported similar results. CONCLUSIONS: Prostaglandin analogues do not offer an
effective alternative for management of retained placenta.
PMID- 29939399
TI - Zinc oxide nanoparticles as contrast-enhancing agents for microwave imaging.
AB - PURPOSE: Microwave imaging/sensing is an emerging technology that shows potential
for healthcare diagnostic applications, particularly in breast cancer detection.
This technique estimates the anatomically variant dielectric properties of the
breast. Similar to other imaging modalities, nanoparticles (NPs) could
potentially be utilized as contrast agents to increase contrast between healthy
and malignant tissues. METHODS: In this study, aqueous suspensions of NPs such as
surface-modified single-walled carbon nanotubes, zinc oxide, and silicon dioxide
are studied to assess their potential effective contrast for microwave imaging.
Morphology characterization of the NPs has been achieved using atomic force
microscopy (AFM) and scanning electron microscopy (SEM). The size and stability
of colloidal dispersions have been characterized by dynamic light scattering
technique (DLS) and Ultraviolet-visible spectrophotometry (UV-Vis). The
dielectric characterization of the aqueous-based colloidal suspensions is
recorded over the microwave frequency range between 1 and 4 GHz. RESULTS: Zinc
oxide NP dispersion has shown an increase in the dielectric constant compared to
the background medium. Furthermore, PEGylation of ZnO NPs can achieve a valid
increase in the dielectric constant compared to water, which was shown to be
concentration dependent. CONCLUSION: These results suggest that ZnO nanomaterials
have the potential to be used in biomedical applications such as breast imaging
to improve diagnostic capabilities.
PMID- 29939401
TI - Prague Special Issue.
PMID- 29939400
TI - Cushing's disease in older patients: Presentation and outcome.
AB - BACKGROUND: To define the symptoms, signs and treatment outcomes in a population
of older patients with Cushing's disease (CD). METHODS: We analysed the clinical
presentation and treatment outcomes in 45 CD patients older than 60 years, in
comparison with 90 CD patients younger than 60, and a control group of 45 older
patients with nonfunctioning pituitary adenomas. We reviewed preoperative
clinical characteristics, medical comorbidities, imaging findings and endocrine
testing as well as surgical and endocrine outcomes. RESULTS: Older CD patients
had significantly lower body mass index (BMI) (P = 0.031), were more likely to
have muscle wasting (P = 0.006) and women were less likely to have hirsutism (P =
0.033). Older patients with CD had more medical comorbidities than younger
patients, which correlated with a higher ASA grade (P < 0.001), but the surgical
complication rates were similar in both groups. Surgical remission was achieved
in 38/45 (84.4%) older patients and 78/90 (86.7%) younger patients (P = NS).
Recurrent disease was more frequent in younger patients (19.2%) in comparison
with older patients (2.6%, P = 0.019). CONCLUSIONS: Older patients with CD appear
to have a distinct phenotype with a more catabolic picture, including a lower BMI
and greater prevalence of muscle wasting. Surgical outcomes are similar without a
significant age-related increase in complications.
PMID- 29939402
TI - Count statistics of nonparalyzable photon-counting detectors with nonzero pulse
length.
AB - PURPOSE: Photon-counting detectors are expected to be the next big step in the
development of medical computed tomography (CT). Accurate modeling of the
behavior of photon-counting detectors in both low and high count rate regimes is
important for accurate image reconstruction and detector performance evaluations.
The commonly used ideal nonparalyzable (delta pulse) model is built on crude
assumptions that make it unsuitable for predicting the behavior of photon
counting detectors at high count rates. The aim of this work is to present an
analytical count statistics model that better describes the behavior of photon
counting detectors with nonzero pulse length. METHODS: An analytical statistical
count distribution model for nonparalyzable detectors with nonzero pulse length
is derived using tools from statistical analysis. To validate the model, a
nonparalyzable photon-counting detector is simulated using Monte Carlo methods
and compared against. Image performance metrics are computed using the Fisher
information metric and a comparison between the proposed model, approximations of
the proposed model, and those made by the ideal nonparalyzable model is presented
and analyzed. RESULTS: It is shown that the presented model agrees well with the
results from the Monte Carlo simulation and is stable for varying x-ray beam
qualities. It is also shown that a simple Gaussian approximation of the
distribution can be used to accurately model the behavior and performance of
nonparalyzable detectors with nonzero pulse length. Furthermore, the comparison
of performance metrics show that the proposed model predicts a very different
behavior than the ideal nonparalyzable detector model, suggesting that the
proposed model can fill an important gap in the understanding of pileup effects.
CONCLUSIONS: An analytical model for the count statistics of a nonparalyzable
photon-counting detector with nonzero pulse length is presented. The model agrees
well with results obtained from Monte Carlo simulations and can be used to
improve, speed up and simplify modeling of photon-counting detectors.
PMID- 29939403
TI - Glatiramer acetate-specific antibody titres in patients with relapsing /
remitting multiple sclerosis and in experimental autoimmune encephalomyelitis.
PMID- 29939404
TI - Enzymatic Modification of Rice Bran Polysaccharides by Enzymes from Grifola
Frondosa: Natural Killer Cell Cytotoxicity and Antioxidant Activity.
AB - : Rice bran polysaccharides (RBPSs) are the major active constituents of rice
bran (RB). In this study, we utilized intracellular enzymes from Grifola frondosa
to modify RBPSs, which were extracted from RB using ultrasound. To enhance the
effect on natural killer (NK) cell cytotoxicity of modified polysaccharides
(mRBPSs) generated from RBPSs, an orthogonal test (L9 [3]4 ) was employed to
optimize the modification conditions. Based on the results of a single-factor
test, the enzyme to polysaccharide ratio, reaction temperature, reaction pH, and
reaction time were the main factors affecting mRBPSs-enhanced NK-cell
cytotoxicity. The best conditions were determined to be an enzyme to
polysaccharide ratio of 1:5, a reaction temperature of 40 degrees C, a reaction
pH of 4, and a reaction time of 4 hr. By optimizing the conditions, the NK-cell
cytotoxicity induced by mRBPSs6 was the highest, increasing by 12.01% +/- 0.08%.
Gas chromatographic analysis revealed that mRBPSs6 consists of rhamnose,
arabinose, xylose, mannose, glucose, and galactose at a molar ratio of
7:21:6:5:53:48, which was 8:13:8:5:44:44 before modification. High-performance
liquid chromatography results indicated molecular weights for the RBPSs of
approximately 106 Da, which decreased to 104 to 105 Da after modification.
Antioxidant activity tests revealed high capacity of mRBPSs6 for scavenging 1,1
diphenyl-2-picrylhydrazyl radicals and hydroxyl free radicals at 1.0 mg/mL.
PRACTICAL APPLICATION: Rice bran polysaccharides (RBPSs) contain compounds with
many biological activities. However, these polysaccharides difficult to absorb
due to high molecular weights and unexposed active sites, which are the main
factors that limit their use in functional foods. The results of this study
demonstrate that modification of RBPSs using intracellular enzymes from an edible
fungus alters the molecular weights and monosaccharide composition of RBPSs. In
addition, immune and antioxidant activities of RBPSs were increased. The findings
provide a new and beneficial application for rice bran.
PMID- 29939405
TI - Bruno Kyewski 1950-2018.
PMID- 29939406
TI - Botulinum toxins for the prevention of migraine in adults.
AB - BACKGROUND: Migraine occurs in around 15% of adults and is ranked as the seventh
most disabling disease amongst all diseases globally. Despite the available
treatments many people suffer prolonged and frequent attacks which have a major
impact on their quality of life. Chronic migraine is defined as 15 or more days
of headache per month, at least eight of those days being migraine. People with
episodic migraine have fewer than 15 headache days per month. Botulinum toxin
type A has been licensed in some countries for chronic migraine treatment, due to
the results of just two trials. OBJECTIVES: To assess the effects of botulinum
toxins versus placebo or active treatment for the prevention or reduction in
frequency of chronic or episodic migraine in adults. SEARCH METHODS: We searched
CENTRAL, MEDLINE & MEDLINE in Process, Embase, ClinicalTrials.gov and World
Health Organization International Clinical Trials Registry (to December 2017). We
examined reference lists and carried out citation searches on key publications.
We sent correspondence to major manufacturers of botulinum toxin. SELECTION
CRITERIA: Randomised, double-blind, controlled trials of botulinum toxin (any
sero-type) injections into the head and neck for prophylaxis of chronic or
episodic migraine in adults. Eligible comparators were placebo, alternative
prophylactic agent or different dose of botulinum toxin. DATA COLLECTION AND
ANALYSIS: Two review authors independently selected trials and extracted data.
For continuous outcomes we used mean change data when available. For dichotomous
data we calculated risk ratios (RRs). We used data from the 12-week post
treatment follow-up time point. We assessed the evidence using GRADE and created
two 'Summary of findings' tables. MAIN RESULTS: Description of trialsWe found 90
articles describing 28 trials (4190 participants), which were eligible for
inclusion. The longest treatment duration was three rounds of injections with
three months between treatments, so we could not analyse long-term effects. For
the primary analyses, we pooled data from both chronic and episodic participant
populations. Where possible, we also separated data into chronic migraine,
episodic migraine and 'mixed group' classification subgroups. Most trials (21 out
of 28) were small (fewer than 50 participants per trial arm). The risk of bias
for included trials was low or unclear across most domains, with some trials
reporting a high risk of bias for incomplete outcome data and selective outcome
reporting.Botulinum toxin versus placeboTwenty-three trials compared botulinum
toxin with placebo. Botulinum toxin may reduce the number of migraine days per
month in the chronic migraine population by 3.1 days (95% confidence interval
(CI) -4.7 to -1.4, 4 trials, 1497 participants, low-quality evidence). This was
reduced to -2 days (95% CI -2.8 to -1.1, 2 trials, 1384 participants; moderate
quality evidence) when we removed small trials.A single trial of people with
episodic migraine (N = 418) showed no difference between groups for this outcome
measure (P = 0.49).In the chronic migraine population, botulinum toxin reduces
the number of headache days per month by 1.9 days (95% CI -2.7 to -1.0, 2 trials,
1384 participants, high-quality evidence). We did not find evidence of a
difference in the number of migraine attacks for both chronic and episodic
migraine participants (6 trials, N = 2004, P = 0.30, low-quality evidence). For
the population of both chronic and episodic migraine participants a reduction in
severity of migraine rated during clinical visits, on a 10 cm visual analogue
scale (VAS) of 3.3 cm (95% CI -4.2 to -2.5, very low-quality evidence) in favour
of botulinum toxin treatment came from four small trials (N = 209); better
reporting of this outcome measure from the additional eight trials that recorded
it may have improved our confidence in the pooled estimate. Global assessment and
quality-of-life measures were poorly reported and it was not possible to carry
out statistical analysis of these outcome measures. Analysis of adverse events
showed an increase in the risk ratio with treatment with botulinum toxin over
placebo 30% (RR 1.28, 95% CI 1.12 to 1.47, moderate-quality evidence). For every
100 participants 60 experienced an adverse event in the botulinum toxin group
compared with 47 in the placebo group.Botulinum toxin versus other prophylactic
agentThree trials studied comparisons with alternative oral prophylactic
medications. Meta-analyses were not possible for number of migraine days, number
of headache days or number of migraine attacks due to insufficient data, but
individually trials reported no differences between groups for a variety of
efficacy measures in the population of both chronic and episodic migraine
participants. The global impression of disease measured using Migraine Disability
Assessment (MIDAS) scores were reported from two trials that showed no difference
between groups. Compared with oral treatments, botulinum toxin showed no between
group difference in the risk of adverse events (2 trials, N = 114, very low
quality evidence). The relative risk reduction (RRR) for withdrawing from
botulinum toxin due to adverse events compared with the alternative prophylactic
agent was 72% (P = 0.02, 2 trials, N = 119).Dosing trialsThere were insufficient
data available for the comparison of different doses.Quality of the evidenceThe
quality of the evidence assessed using GRADE methods was varied but mostly very
low; the quality of the evidence for the placebo and active control comparisons
was low and very low, respectively for the primary outcome measure. Small trial
size, high risk of bias and unexplained heterogeneity were common reasons for
downgrading the quality of the evidence. AUTHORS' CONCLUSIONS: In chronic
migraine, botulinum toxin type A may reduce the number of migraine days per month
by 2 days compared with placebo treatment. Non-serious adverse events were
probably experienced by 60/100 participants in the treated group compared with
47/100 in the placebo group. For people with episodic migraine, we remain
uncertain whether or not this treatment is effective because the quality of this
limited evidence is very low. Better reporting of outcome measures in published
trials would provide a more complete evidence base on which to draw conclusions.
PMID- 29939407
TI - Evidence of altered depression and dementia-related proteins in the brains of
young rats after ovariectomy.
AB - Menopause, a risk factor for brain dysfunction in women, is characterized by
neuropsychological symptoms including depression and dementia, which are closely
related to alterations in different brain regions after menopause. However,
little is known about the variability in pathophysiologic changes associated with
menopause in the brain. Here, we observed that menopause in rats induced by
bilateral ovariectomy (OVX) showed depressive and dementia-related behaviors
along with neuronal loss in the prefrontal cortex (PFC), hippocampus (HIP),
hypothalamus (HYP), and amygdala (AMY) by Nissl staining. Meanwhile, by
immunohistochemical staining, increased microglia in the HIP and AMY and
increased astrocytes in the PFC, HYP, and AMY were shown. Using quantitative
proteomics, we identified 146 differentially expressed proteins in the brains of
OVX rats, for example, 20 in the PFC, 41 in the HIP, 17 in the HYP, and 79 in the
AMY, and performed further detection by western blotting. A link between neuronal
loss and apoptosis was suggested, as evidenced by increases in adenylate kinase 2
(AK2), B-cell lymphoma 2 associated X (Bax), cleaved caspase 3, and
phosphorylated p53 and decreases in Huntingtin-interacting protein K, hexokinase,
and phosphorylated B-cell lymphoma 2 (Bcl-2), and apoptosis might be triggered by
endoplasmic reticulum stress (probed by increased glucose-regulated protein 78
(GRP78), cleaved caspase 12, phosphorylated protein kinase R (PKR)-like
endoplasmic reticulum kinase, inositol-requiring enzyme-1 and activating
transcription factor 6), and mitochondrial dysfunction (probed by increased
cytochrome c and cleaved caspase 3 and decreased sideroflexin-1 (SFXN1) and NADH
dehydrogenase (ubiquinone) 1 alpha subcomplex 11 (NDUFA11)). Activation of
autophagy was also indicated by increased autophagy-related 7, gamma-aminobutyric
acid (GABA) receptor-associated protein-like 2, and oxysterol-binding protein
related protein 1 and confirmed by increased microtubule-associated protein light
chain 3 (LC3II/I), autophagy-related 5, and Beclin1 in the HIP and AMY. In the
AMY, which is important in emotion, higher GABA transporter 3 and lower vesicular
glutamate transporter 1 levels indicated an imbalance between excitatory and
inhibitory neurotransmission, and the increased calretinin and decreased
calbindin levels suggested an adjustment of GABAergic transmission after OVX. In
addition, cytoskeletal abnormalities including tau hyperphosphorylation,
dysregulated Ca2+ signals, and glutamic synaptic impairments were observed in the
brains of OVX rats. Collectively, our study showed the changes in different brain
regions related to depression and dementia during menopause.
PMID- 29939409
TI - Editorial: real-life data confirm efficacy of elbasvir/grazoprevir in HCV
patients with severe kidney disease-Author's reply.
PMID- 29939408
TI - Letter: impact of HBV genotypes and PC/BCP mutations on serum HBsAg levels in
Chinese HBeAg-negative patients.
PMID- 29939410
TI - Editorial: real-life data confirm efficacy of elbasvir/grazoprevir in HCV
patients with severe kidney disease.
PMID- 29939411
TI - Letter: unlikely liver bedfellows-alpha-1 antitrypsin deficiency and
granulomatosis with polyangiitis.
PMID- 29939413
TI - Letter: direct-acting anti-viral (DAA) therapy needs strong safety and efficacy
check.
PMID- 29939412
TI - Letter: impact of HBV genotypes and PC/BCP mutations on serum HBsAg levels in
Chinese HBeAg negative patients-Authors' reply.
PMID- 29939414
TI - Letter: direct-acting anti-viral (DAA) therapy needs strong safety and efficacy
check-authors' reply.
PMID- 29939415
TI - Editorial: self-dilation for refractory oesophageal strictures is worth
considering-author's reply.
PMID- 29939416
TI - Editorial: frequency of surveillance and survival in hepatocellular carcinoma.
PMID- 29939417
TI - Editorial: frequency of surveillance and survival in hepatocellular carcinoma
authors' reply.
PMID- 29939418
TI - Editorial: self-dilation for refractory oesophageal strictures is worth
considering.
PMID- 29939419
TI - Letter: unlikely liver bedfellows-alpha-1 antitrypsin deficiency and
granulomatosis with polyangiitis. Author's reply.
PMID- 29939421
TI - The time lag prior to the rise in glucose requirements to maintain stable
glycaemia during moderate exercise in a fasted insulinaemic state is of short
duration and unaffected by the level at which glycaemia is maintained in Type 1
diabetes.
AB - AIMS: To determine the duration of the low hypoglycaemia risk period after the
start of moderate-intensity exercise performed under basal insulinaemic
conditions and whether this period is affected by the level at which glycaemia is
maintained under these conditions. METHODS: This was a prospective, randomized
counterbalanced study. Eight participants with Type 1 diabetes (mean +/- sd age
21.5 +/- 4.0 years) underwent either a euglycaemic (5-6 mmol/l) or hyperglycaemic
clamp (9-10 mmol/l) on separate days and were infused with insulin at basal rates
and [6,6-2 H]glucose while cycling for 40 min at 50% maximum oxygen consumption
rate. The main outcome measures were the glucose infusion rates required to
maintain stable glycaemia and glucoregulatory hormone levels, and rates of
glucose appearance and disappearance. RESULTS: During the first 20 min of
exercise, the glucose infusion rate did not increase significantly, irrespective
of the level at which glycaemia was maintained, but increased acutely between 20
and 25 min under both conditions. Maintaining higher glycaemia resulted in higher
glucose infusion rate during, but not early post-exercise. With the exception of
epinephrine, the glucoregulatory hormone levels and rates of glucose appearance
and disappearance were similar between conditions. CONCLUSION: Irrespective of
the levels at which glycaemia is maintained, there is a 20-min low exogenous
glucose demand period during which the exogenous glucose requirements to maintain
stable glycaemia do not increase during moderate exercise performed at basal
insulin level.
PMID- 29939422
TI - Long-term effects and recovery of streams from acid mine drainage and evaluation
of toxic metal threshold ranges for macroinvertebrate community reassembly.
AB - Monitoring of benthic invertebrates in streams receiving acidic metal
contaminated water over an 18-yr period revealed both degraded conditions and
recovery along a network of downstream locations. Compared with reference
streams, and over the course of clean-up remediation efforts below an abandoned
open-pit sulfur mine in the central Sierra Nevada of California, improving water
quality was accompanied by recovery of benthic communities at some sites. Years
of high flow resulted in degraded biological status when acid mine drainage
capture was incomplete and metal loading had increased with runoff. Seasonal
patterns of recovery evident in the fall after the summer treatment season
reverted in the next spring after overwinter periods when sources were not
captured. As the metal load has been reduced, phased recovery of community
structure, function, and similarity progressed toward that of reference
assemblage taxonomic composition. From impacted communities dominated by
relatively tolerant midges, reassembly involved an increase in density, return of
long-lived taxa, an increased ratio of sensitive-to-tolerant forms, then overall
diversity and community composition, and eventually large predators and grazers
reappearing along with mayfly, stonefly, and caddisfly richness. Threshold effect
levels defined using several analysis methods showed that the response range of
biological indicators corresponds to US Environmental Protection Agency
guidelines of predicted effects utilizing cumulative criterion units (CCUs) of
metal toxicity (i.e., CCU ~ 1). All sites have shown improved function with
increased density of some or all trophic groups over time. Although recovery is
progressing, year-around treatment may be necessary to fully restore biological
integrity in streams nearest the mine. Environ Toxicol Chem 2018;37:2575-2592.
(c) 2018 SETAC.
PMID- 29939423
TI - Emerging areas of opioid pharmacology.
AB - : This themed section of the British Journal of Pharmacology stems from an
International Narcotics Research Conference (INRC) meeting held in July 2016 at
The Assembly Rooms in Bath, UK. LINKED ARTICLES: This article is part of a themed
section on Emerging Areas of Opioid Pharmacology. To view the other articles in
this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.
PMID- 29939425
TI - Tough Hydrogels with Fast, Strong, and Reversible Underwater Adhesion Based on a
Multiscale Design.
AB - Hydrogels have promising applications in diverse areas, especially wet
environments including tissue engineering, wound dressing, biomedical devices,
and underwater soft robotics. Despite strong demands in such applications and
great progress in irreversible bonding of robust hydrogels to diverse synthetic
and biological surfaces, tough hydrogels with fast, strong, and reversible
underwater adhesion are still not available. Herein, a strategy to develop
hydrogels demonstrating such characteristics by combining macroscale surface
engineering and nanoscale dynamic bonds is proposed. Based on this strategy,
excellent underwater adhesion performance of tough hydrogels with dynamic ionic
and hydrogen bonds, on diverse substrates, including hard glasses, soft
hydrogels, and biological tissues is obtained. The proposed strategy can be
generalized to develop other soft materials with underwater adhesion.
PMID- 29939426
TI - Effects of regional enamel and prism orientations on bovine enamel bond strength
and cohesive strength.
AB - This study investigated the regional microtensile bond strength (MTBS) and
cohesive strength of bovine enamel. The crowns of bovine incisors were sectioned,
either horizontally along incisal and cervical thirds to produce horizontal and
tangential segments, or longitudinally along the midline to produce longitudinal
segments. Half of the horizontal and longitudinal segments were prepared using a
45 degrees bevel. Then, the differently sectioned enamel surfaces were treated
with one- or two-step self-etch adhesives (Clearfil SE Bond or Clearfil S3 Bond)
and a composite resin (Clearfil Majesty) was placed. Resin-bonded enamel samples
were cut into beams for use in the MTBS tests. Labial horizontal and longitudinal
segments of pure enamel beams were prepared for cohesive strength tests. Enamel
microstructures were analyzed by scanning electron microscopy. Three-way anova
followed by Tukey's post-hoc HSD multiple comparisons procedure showed that a 45
degrees bevel cut did not statistically significantly improve enamel MTBS, which
varied with the different regions. The longitudinally sectioned resin-bonded
enamel samples had the lowest MTBS, and the horizontal enamel cohesive strength
was weaker than that of the longitudinal enamel. The scanning electron microscopy
fractographs indicated that rows of parallel prisms were detached from the
fractured surfaces. In conclusion, the regional enamel MTBS and the cohesive
strength are strongly related to the enamel microstructures and prism
orientations.
PMID- 29939427
TI - Lanthanide Contraction as a Design Factor for High-Performance Half-Heusler
Thermoelectric Materials.
AB - Forming solid solutions, as an effective strategy to improve thermoelectric
performance, has a dilemma that alloy scattering will reduce both the thermal
conductivity and carrier mobility. Here, an intuitive way is proposed to decouple
the opposite effects, that is, using lanthanide contraction as a design factor to
select alloying atoms with large mass fluctuation but small radius difference
from the host atoms. Typical half-Heusler alloys, n-type (Zr,Hf)NiSn and p-type
(Nb,Ta)FeSb solid solutions, are taken as paradigms to attest the validity of
this design strategy, which exhibit greatly suppressed lattice thermal
conductivity and maintained carrier mobility. Furthermore, by considering
lanthanide contraction, n-type (Zr,Hf)CoSb-based alloys with high zT of ~1.0 are
developed. These results highlight the significance of lanthanide contraction as
a design factor in enhancing the thermoelectric performance and reveal the
practical potential of (Zr,Hf)CoSb-based half-Heusler compounds due to the
matched n-type and p-type thermoelectric performance.
PMID- 29939429
TI - Co-occurrence of astrocytoma and astroblastoma: Case report and literature
review.
AB - A 41-year-old man presented to us with left arm and leg weakness and mild word
finding difficulties. His preoperative magnetic resonance imaging (MRI)
demonstrated abnormal T1 and T2 signal changes in the right temporal lobe and
basal ganglia, indicative of possible glioma. An awake craniotomy for right
temporal lobectomy was performed and the tumor was resected. Full pathologic
workup later revealed the patient had two distinct tumors occurring
simultaneously, anaplastic astrocytoma and astroblastoma. We review the
literature regarding the treatment of anaplastic astrocytoma and astroblastoma
and discuss their co-occurrence.
PMID- 29939428
TI - Highly Branched VS4 Nanodendrites with 1D Atomic-Chain Structure as a Promising
Cathode Material for Long-Cycling Magnesium Batteries.
AB - Rechargeable magnesium batteries have attracted increasing attention due to the
high theoretical volumetric capacities, dendrite formation-free characteristic
and low cost of Mg metal anodes. However, the development of magnesium batteries
is seriously hindered by the lack of capable cathode materials with long cycling
life and fast solid-state diffusion kinetics for highly-polarized divalent Mg2+
ions. Herein, vanadium tetrasulfide (VS4 ) with special one-dimensional atomic
chain structure is reported to be able to serve as a favorable cathode material
for high-performance magnesium batteries. Through a surfactant-assisted solution
phase process, sea-urchin-like VS4 nanodendrites are controllably prepared.
Benefiting from the chain-like crystalline structure of VS4 , the S22- dimers in
the VS4 nanodendrites provide abundant sites for Mg2+ insertion. Moreover, the
VS4 atomic-chains bonded by weak van der Waals forces are beneficial to the
diffusion kinetics of Mg2+ ions inside the open channels of VS4 . Through a
series of systematic ex situ characterizations and density functional theory
calculations, the magnesiation/demagnesiation mechanism of VS4 are elucidated.
The VS4 nanodendrites present remarkable performance for Mg2+ storage among
existing cathode materials, exhibiting a remarkable initial discharge capacity of
251 mAh g-1 at 100 mA g-1 and an impressive long-term cyclability at large
current density of 500 mA g-1 (74 mAh g-1 after 800 cycles).
PMID- 29939430
TI - Enantiomeric separation of beta-blockers and tryptophan using heparin as
stationary and pseudostationary phases in capillary electrophoresis.
AB - The separation methods of the enantiomers of two beta-blockers and tryptophan
were studied using capillary electrochromatography with heparin covalently as
well as non-covalently, bonded onto the capillary inner wall as stationary phase
and electrokinetic chromatography with heparin as pseudostationary phase. In the
case of heparin, used as a stationary phase, the method was unable to resolve
enantiomers in both cases beta-blockers and tryptophan. On the other hand, when
heparin was used as a pseudostationary phase, the resolution of the enantiomers
was obtained only with 3-aminopropyltriethoxysilane which were immobilised onto
the inner phase of the capillary. The results of this study let us infer that the
electrostatic, hydrophobic, and steric interactions were involved in the
separation mechanisms. The separation was achieved in less than 10 minutes under
the optimized conditions: 30 mM phosphate buffer (pH 2.5) with the adding of 15
mg/mL of heparin at 15 degrees C and 10 kV. The usefulness of heparin as a chiral
selector both in electrokinetic chromatography using 3-aminopropyltriethoxysilane
attached to the capillary was demonstrated for the first time. The developed
method was powerful, sensitive, and fast, and it could be considered an important
alternative to conventional methods used for chiral separation.
PMID- 29939431
TI - Sugar Acetonides are a Superior Motif for Addressing the Large, Solvent-Exposed
Ribose-33 Pocket of tRNA-Guanine Transglycosylase.
AB - The intestinal disease shigellosis caused by Shigella bacteria affects over 120
million people annually. There is an urgent demand for new drugs as resistance
against common antibiotics emerges. Bacterial tRNA-guanine transglycosylase (TGT)
is a druggable target and controls the pathogenicity of Shigella flexneri. We
report the synthesis of sugar-functionalized lin-benzoguanines addressing the
ribose-33 pocket of TGT from Zymomonas mobilis. Ligand binding was analyzed by
isothermal titration calorimetry and X-ray crystallography. Pocket occupancy was
optimized by variation of size and protective groups of the sugars. The
participation of a polycyclic water-cluster in the recognition of the sugar
moiety was revealed. Acetonide-protected ribo- and psicofuranosyl derivatives are
highly potent, benefiting from structural rigidity, good solubility, and
metabolic stability. We conclude that sugar acetonides have a significant but not
yet broadly recognized value in drug development.
PMID- 29939432
TI - Synthesis and Field-Effect Transistor Application of pi-Extended Lactam-Fused
Conjugated Oligomers obtained by Tandem Direct Arylation.
AB - Five pi-extended lactam-fused conjugated oligomers (5FO, 5FS, 4FPO, 4FPS, and R
4FPO) were synthesized by the tandem direct arylation. The intermolecular
oxidative direct arylation was applied in the second step. These conjugated
oligomers had fine-tuned FMO energies predictable by the theoretical calculation
and excellent thermal stabilities. 4FPO and 4FPS bearing tetrafluoropyridine
exhibited lower LUMO energy levels (-3.20 eV and -3.39 eV, respectively) compared
with others. Based on the X-ray crystallography, 4FPO was found to have a
herringbone crystal packing and a considerably large electron transfer integral
value (137 meV). 4FPO-based bottom-gate, bottom-contact FET device demonstrated
an electron mobility of 5.2*10-3 cm2 V-1 s-1 as a result of an edge-on
alignment on the SiO2 substrate.
PMID- 29939433
TI - A Silica-Aerogel-Reinforced Composite Polymer Electrolyte with High Ionic
Conductivity and High Modulus.
AB - High-energy all-solid-state lithium (Li) batteries have great potential as next
generation energy-storage devices. Among all choices of electrolytes, polymer
based systems have attracted widespread attention due to their low density, low
cost, and excellent processability. However, they are generally mechanically too
weak to effectively suppress Li dendrites and have lower ionic conductivity for
reasonable kinetics at ambient temperature. Herein, an ultrastrong reinforced
composite polymer electrolyte (CPE) is successfully designed and fabricated by
introducing a stiff mesoporous SiO2 aerogel as the backbone for a polymer-based
electrolyte. The interconnected SiO2 aerogel not only performs as a strong
backbone strengthening the whole composite, but also offers large and continuous
surfaces for strong anion adsorption, which produces a highly conductive pathway
across the composite. As a consequence, a high modulus of ~0.43 GPa and high
ionic conductivity of ~0.6 mS cm-1 at 30 degrees C are simultaneously achieved.
Furthermore, LiFePO4 -Li full cells with good cyclability and rate capability at
ambient temperature are obtained. Full cells with cathode capacity up to 2.1 mAh
cm-2 are also demonstrated. The aerogel-reinforced CPE represents a new design
principle for solid-state electrolytes and offers opportunities for future all
solid-state Li batteries.
PMID- 29939434
TI - Four-Oil Lipid Emulsion (Smoflipid) as a Tool in Managing Parenteral Nutrition
Shortages.
PMID- 29939435
TI - Interlayer-Spacing-Regulated VOPO4 Nanosheets with Fast Kinetics for High
Capacity and Durable Rechargeable Magnesium Batteries.
AB - Owing to the low-cost, safety, dendrite-free formation, and two-electron redox
properties of magnesium (Mg), rechargeable Mg batteries are considered as
promising next-generation secondary batteries with high specific capacity and
energy density. However, the clumsy Mg2+ with high polarity inclines to sluggish
Mg insertion/deinsertion, leading to inadequate reversible capacity and rate
performance. Herein, 2D VOPO4 nanosheets with expanded interlayer spacing (1.42
nm) are prepared and applied in rechargeable magnesium batteries for the first
time. The interlayer expansion provides enough diffusion space for fast kinetics
of MgCl+ ion flux with low polarization. Benefiting from the structural
configuration, the Mg battery exhibits a remarkable reversible capacity of 310
mAh g-1 at 50 mA g-1 , excellent rate capability, and good cycling stability (192
mAh g-1 at 100 mA g-1 even after 500 cycles). In addition, density functional
theory (DFT) computations are conducted to understand the electrode behavior with
decreased MgCl+ migration energy barrier compared with Mg2+ . This approach,
based on the regulation of interlayer distance to control cation insertion,
represents a promising guideline for electrode material design on the development
of advanced secondary multivalent-ion batteries.
PMID- 29939436
TI - Enlarged Co?O Covalency in Octahedral Sites Leading to Highly Efficient Spinel
Oxides for Oxygen Evolution Reaction.
AB - Cobalt-containing spinel oxides are promising electrocatalysts for the oxygen
evolution reaction (OER) owing to their remarkable activity and durability.
However, the activity still needs further improvement and related fundamentals
remain untouched. The fact that spinel oxides tend to form cation deficiencies
can differentiate their electrocatalysis from other oxide materials, for example,
the most studied oxygen-deficient perovskites. Here, a systematic study of spinel
ZnFex Co2-x O4 oxides (x = 0-2.0) toward the OER is presented and a highly active
catalyst superior to benchmark IrO2 is developed. The distinctive OER activity is
found to be dominated by the metal-oxygen covalency and an enlarged Co?O
covalency by 10-30 at% Fe substitution is responsible for the activity
enhancement. While the pH-dependent OER activity of ZnFe0.4 Co1.6 O4 (the optimal
one) indicates decoupled proton-electron transfers during the OER, the
involvement of lattice oxygen is not considered as a favorable route because of
the downshifted O p-band center relative to Fermi level governed by the spinel's
cation deficient nature.
PMID- 29939437
TI - The association of insomnia and depressive symptoms with all-cause mortality
among middle-aged and old adults.
AB - OBJECTIVES: Insomnia and depressive symptoms are commonly reported by adults and
have independently been found to be associated with mortality, though contrasting
findings are reported. Given the high comorbidity and interrelatedness between
these symptoms, we tested whether insomnia symptoms explain risk of death
independent of depressive symptoms. We examined insomnia symptoms and depressive
symptoms, in addition to other health and demographic covariates, as predictors
of all-cause mortality. METHODS: The sample included 15 418 adults aged 51 and
older drawn from a nationally representative, population-based study of adults in
the United States, the Health and Retirement Study. Cox survival models were used
to analyze time to death between the 2002 and 2014 study waves (5 waves).
Controlling for health and demographic covariates, in 3 separate models,
depressive symptoms and insomnia symptoms were independently and then together
considered as risk factors for all-cause mortality (drawn from the National Death
Index). RESULTS: After adjustment for covariates, insomnia symptoms (HR = 1.10,
CI:1.07-1.13) and depressive symptoms (HR = 1.14, CI:1.12-1.16) each were
associated with a greater hazard of death. When considered together, however,
depressive symptoms fully accounted for the association between insomnia symptoms
and mortality. CONCLUSION: Though their effects are small relative to health and
demographic characteristics, both insomnia symptoms and depressive symptoms were
associated with a greater hazard of death. Yet depressive symptoms accounted for
the insomnia association when both were considered in the model. Screening for
depression and providing validated treatments may reduce mortality risk in old
adults with depressive symptoms.
PMID- 29939438
TI - Overcoming the Inertness of Iridium(III) in a Facile Single-Crystal to Single
Crystal Reaction of Iodine Vapor with a Cyclometalated Chloride Monomer.
AB - Iridium(III) is often considered to be one of the most inert octahedral metal
ions. Herein we present a phenanthroimidazole-based bis-cyclometalated
iridium(III) chloride undergoing a facile chloro ligand exchange with iodine, in
a gas-solid reaction under ambient conditions. Monitoring the progress of the
reaction by X-ray diffraction analysis reveals the crystal-packing-induced
exceptional stereoselectivity of this topochemical transformation. The results
provide excellent opportunities to modulate the geometry and kinetic properties
of cyclometalated iridium(III) complexes that may be very promising in catalysis
and design of anticancer agents.
PMID- 29939439
TI - Lessons learned from lifestyle prevention trials in gestational diabetes
mellitus.
AB - Gestational diabetes mellitus (GDM) is associated with an increased risk of
adverse outcomes for mother and infant both at birth and later in life. A large
body of evidence is now available relating to antenatal prevention of GDM.
Overall, despite some individual trials of a variety of lifestyle interventions
revealing benefit, many more have shown no effect from the second trimester
onwards, even with significant gestational weight gain limitation. At-risk women
often seem reluctant to engage in lifestyle changes and frequently cannot adhere
to recommended interventions even within a clinical trial setting. Many trials
have not considered the heterogeneity of diabetes first discovered in pregnancy,
something of importance into the future. Future work should focus on designing
interventions acceptable to the population at risk, whether those taking place
before or during the first trimester of pregnancy are effective, and whether
greater individualization can identify those women most likely to benefit.
PMID- 29939440
TI - Lamellar Liquid Crystals of In-Plane Lying Rod-Like Mesogens with Designer Side
Chains: The Case of Sliding versus Locked Layers.
AB - The dimensionality of self-assembled nanostructures plays an essential role for
their properties and applications. Herein, an understanding of the transition
from weakly to strongly coupled layers in soft matter systems is provided
involving in-plane organized pi-conjugated rods. For this purpose,
bolaamphiphilic triblock molecules consisting of a rigid biphenyl core, polar
glycerol groups at the ends, and a branched (swallow-tail) or linear alkyl or
semiperfluoroalkyl chain in lateral position have been synthesized and
investigated. Besides weakly coupled lamellar isotropic (LamIso ), lamellar
nematic (LamN ) and sliding lamellar smectic phases (LamSm ), a sequence of three
distinct types of strongly coupled (correlated) lamellar smectic phases with
either centered (c2mm) or non-centered rectangular (p2mm) lattice and an
intermediate oblique lattices (p2) were observed depending on chain length, chain
branching and degree of chain fluorination. This new sequence is explained by the
strengthening of the layer coupling and the competition between energetic packing
constraints and the entropic contribution of either longitudinal or tangential
fluctuations. This example of directed side chain engineering of small generic
model compounds provides general clues for morphological design of two
dimensional and three-dimensionally coupled lamellar systems involving larger pi
conjugated molecular rods and molecular or supramolecular polymers, being of
actual interest in organic electronics and nanotechnology.
PMID- 29939442
TI - A Novel Sc(OTf)3 -Catalyzed (2+2+1)-Cycloannulation/Aza-Friedel-Crafts Alkylation
Sequence toward Multicyclic 2-Pyrrolines.
AB - The rapid assembly of molecular complexity continues to be at the forefront of
novel reaction development. In the pursuit of that goal, we herein report a novel
Sc(OTf)3 -catalyzed, one-pot multicomponent reaction that furnishes complex
multicyclic 2-pyrrolines with excellent overall yields and perfect
diastereocontrol. This process is based on our previously established (2+2+1)
cycloannulation of in situ generated 1-azaallyl cations, 1,3-dicarbonyls and
primary amines. The newly formed and highly reactive aminal moiety is readily
substituted with indoles and pyrroles both as external and internal pi
nucleophiles to provide densely functionalized N-heterocycles with four new sigma
bonds and two vicinal quaternary stereogenic centers. In addition, DFT
calculations have been conducted to further characterize the intermediate 1
azaallyl cations.
PMID- 29939441
TI - Atomic Cobalt Covalently Engineered Interlayers for Superior Lithium-Ion Storage.
AB - With the unique-layered structure, MXenes show potential as electrodes in energy
storage devices including lithium-ion (Li+ ) capacitors and batteries. However,
the low Li+ -storage capacity hinders the application of MXenes in place of
commercial carbon materials. Here, the vanadium carbide (V2 C) MXene with
engineered interlayer spacing for desirable storage capacity is demonstrated. The
interlayer distance of pristine V2 C MXene is controllably tuned to 0.735 nm
resulting in improved Li-ion capacity of 686.7 mA h g-1 at 0.1 A g-1 , the best
MXene-based Li+ -storage capacity reported so far. Further, cobalt ions are
stably intercalated into the interlayer of V2 C MXene to form a new interlayer
expanded structure via strong V-O-Co bonding. The intercalated V2 C MXene
electrodes not only exhibit superior capacity up to 1117.3 mA h g-1 at 0.1 A g-1
, but also deliver a significantly ultralong cycling stability over 15 000
cycles. These results clearly suggest that MXene materials with an engineered
interlayer distance will be a rational route for realizing them as superstable
and high-performance Li+ capacitor electrodes.
PMID- 29939443
TI - Strategies for Reversible Guest Uptake and Release from Metallosupramolecular
Architectures.
AB - The cavities of metallosupramolecular cages can be used to mimic the central
spaces of naturally occurring proteins and bind a wide variety of molecular
guests. A range of potential applications have arisen from this capacity for host
guest chemistry. However, to truly harness the opportunities thus afforded,
methodologies to controllably allow the release and reuptake of guests from the
cavities of metallosupramolecular cages are required. Methods to accomplish this
have centered upon reversibly altering the character of either the guest or host.
This minireview outlines the current approaches used to carry out the binding and
release of guests from metallosupramolecular hosts using important examples from
the field.
PMID- 29939444
TI - Excitation-Wavelength-Dependent Emission and Delayed Fluorescence in a Proton
Transfer System.
AB - Manipulating the relaxation pathways of excited states and understanding
mechanisms of photochemical reactions present important challenges in chemistry.
Here we report a unique zinc(II) complex exhibiting unprecedented interplay
between the excitation-wavelength-dependent emission, thermally activated delayed
fluorescence (TADF) and excited state intramolecular proton transfer (ESIPT). The
ESIPT process in the complex is favoured by a short intramolecular OH???N
hydrogen bond. Synergy between the excitation-wavelength-dependent emission and
ESIPT arises due to heavy zinc atom favouring intersystem crossing (isc). Reverse
intersystem crossing (risc) and TADF are favoured by a narrow singlet-triplet
gap, DeltaEST ~10 kJ mol-1 . These results provide the first insight into how a
proton-transfer system can be modified to show a synergy between the excitation
wavelength-dependent emission, ESIPT and TADF. This strategy offers new
perspectives for designing ESIPT and TADF emitters exhibiting tunable excitation
wavelength-dependent luminescence.
PMID- 29939445
TI - The JAK1/JAK2- inhibitor ruxolitinib inhibits mast cell degranulation and
cytokine release.
AB - BACKGROUND: Mastocytosis is characterized by the accumulation of aberrant mast
cells (MC). Patients suffering from mastocytosis suffer from a wide range of
symptoms due to increased levels of MC mediators. It would therefore be of great
benefit to inhibit MC mediator release. However, to date there are few drugs
available that are known to effectively lower MC mediator levels. The evidence
for the involvement of the janus kinase 2 (JAK2)-signal transducer and activation
of transcription 5 (STAT5) signalling pathway in MC activation is slowly
accumulating. Interference with the JAK2-STAT5 pathway might inhibit MC mediator
release. Ruxolitinib, a JAK1/JAK2 inhibitor, indeed decreases symptoms like
pruritus and fatigue in patients with myeloproliferative neoplasms. Yet, detailed
studies on how ruxolitinib affects human mast cell activity are lacking.
OBJECTIVE: To investigate the effect of JAK1/2-inhibition with ruxolitinib in the
human mast cell lines LAD2 and HMC1. METHODS: LAD2 and HMC1 were stimulated with
substance P, codeine or the calcium ionophore A23817. The effect of ruxolitinib
on mast cell degranulation (via measurement of beta-hexosaminidase, histamine
release and CD63 membrane expression) and IL-6, IL-13, MCP-1 and TNF-alpha
production was investigated. The involvement of STAT5 activation was explored
using the selective STAT5 inhibitor pimozide. RESULTS: Ruxolitinib effectively
inhibited codeine- and substance P-induced degranulation in a concentration
dependent manner. Ruxolitinib also significantly inhibited the production of IL
6, TNF-alpha and MCP-1 as induced by A23817 and substance P. Selective STAT5
inhibition with pimozide resulted in diminished degranulation and inhibition of
cytokine production as induced by A23817 and substance P. CONCLUSIONS & CLINICAL
RELEVANCE: This study demonstrates that the JAK1/JAK2 inhibitor ruxolitinib can
inhibit MCactivity, possibly through prevention of STAT5 activation. This renders
the JAK-STAT pathway as an interesting target for therapy to release symptom
burden in mastocytosis and many other MC mediator-related diseases.
PMID- 29939446
TI - Experience of care for Parkinson's disease in European countries: a survey by the
European Parkinson's Disease Association.
AB - BACKGROUND: Few studies report on the experience of care for patients with
Parkinson's disease (PD) from their own point of view. METHODS: An analysis was
carried out of a survey in 11 European countries on self-reported access to
services and satisfaction with different aspects of care. RESULTS: In all, 1775
people with PD (PwP) participated with disease duration ranging from <1 to 42
years. When referred to a specialist most were seen within 3 months but
medication reviews occurred every 3 months in only 10%, every 6 months in 37%,
once a year in 40% and every 2 years or less frequently in 13%. Waiting times to
therapists were usually >=4 months. Satisfaction with care was highest for
involvement of PwP in decisions (63% of respondents satisfied) and involvement of
family/carer (62%) followed by communication with PwP (57%), information received
(54%), frequency of treatment reviews (52%) and suitability of treatment for the
individual condition and circumstances (52%), but lowest for availability and
accessibility of treatment when needed (48%) and collaborations between
healthcare professionals in delivering care (41% satisfied). The main factors
associated with overall satisfaction scores with care were the overall
satisfaction with initial consultation (r = 0.26, P < 0.0001), the sensitivity
with which the diagnosis was communicated, the quantity of information provided
(both r = 0.24, P < 0.0001) and the frequency of medication review (r = 0.17, P <
0.0001). CONCLUSION: More coordinated and responsive care, tailored to the
individual, with regular and timely medication reviews and information provision,
is likely to improve satisfaction with care in current healthcare pathways.
PMID- 29939447
TI - The choice of universal primers and the characteristics of the species mixture
determine when DNA metabarcoding can be quantitative.
AB - DNA metabarcoding is a technique used to survey biodiversity in many ecological
settings, but there are doubts about whether it can provide quantitative results,
that is, the proportions of each species in the mixture as opposed to a species
list. While there are several experimental studies that report quantitative
metabarcoding results, there are a similar number that fail to do so. Here, we
provide the rationale to understand under what circumstances the technique can be
quantitative. In essence, we simulate a mixture of DNA of S species with a
defined initial abundance distribution. In the simulated PCR, each species
increases its concentration following a certain amplification efficiency. The
final DNA concentration will reflect the initial one when the efficiency is
similar for all species; otherwise, the initial and final DNA concentrations
would be poorly related. Although there are many known factors that modulate
amplification efficiency, we focused on the number of primer-template mismatches,
arguably the most important one. We used 15 common primers pairs targeting the
mitochondrial COI region and the mitogenomes of ca. 1,200 insect species. The
results showed that some primers pairs produced quantitative results under most
circumstances, whereas some other primers failed to do so. In conclusion,
depending on the primer pair used in the PCR amplification and on the
characteristics of the mixture analysed (i.e., high species richness, low
evenness), DNA metabarcoding can provide a quantitative estimate of the relative
abundances of different species.
PMID- 29939448
TI - Chemical Modification of Dehydrated Amino Acids in Natural Antimicrobial Peptides
by Photoredox Catalysis.
AB - Dehydroalanine (Dha) and dehydrobutyrine (Dhb) are remarkably versatile non
canonical amino acids often found in antimicrobial peptides. This work presents
the selective modification of Dha and Dhb in antimicrobial peptides through
photocatalytic activation of organoborates under the influence of visible light.
Ir(dF(CF3 )ppy)2 (dtbbpy)PF6 was used as a photoredox catalyst in aqueous
solutions for the modification of thiostrepton and nisin. The mild conditions and
high selectivity for the dehydrated residues show that photoredox catalysis is a
promising tool for the modification of peptide-derived natural products.
PMID- 29939449
TI - Cell electrofusion to improve efficacy and thermotolerance of the
entomopathogenic fungus, Beauveria bassiana.
AB - AIMS: The aim of this study was to optimize the potential of Beauveria bassiana
through cell electrofusion technique with emphasis on improving its
thermotolerance and virulence against western flower thrips, Frankliniella
occidentalis (Thysanoptera: Thripidae) (WFT). METHODS AND RESULTS: Nine B.
bassiana isolates were tested against western flower thrips, F. occidentalis
(Thysanoptera: Thripidae) (WFT) to estimate their pathogenicity and speed of
infection under laboratory conditions. The isolates were also exposed to 25, 36,
38 and 40 degrees C, for 24, 48, 72 and 120 h. Two isolates with the highest
virulence against WFT and highest thermotolerance were selected and paired using
a cell electrofusion technique to obtain a single strain that was both highly
virulent and thermotolerant. To determine the hybrid conidia among the fusion
cells, each selected isolate was loaded with a different nuclei-staining
fluorescent dye before the fusion process. Hybridized fungal strains were
acquired by a series of sequential dilutions and were tested for thermotolerance
and virulence against WFT. Those that demonstrated both characteristics (high
thermotolerance and virulence) similar to or greater than the parental isolates
were considered hybrids. CONCLUSIONS: The results demonstrated that genetic
transformation using cell electrofusion can be used to obtain hybrid isolates of
fungal pathogens that contain the desired genes from selected isolates. Further
DNA-based analysis is required to determine the genetic variation between hybrids
and the parental isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the
first study to demonstrate genetic transformation in B. bassiana by use of cell
electrofusion and it could be developed to create superior hybrid isolates with
various desired properties for integrated pest management and industrial uses in
the future.
PMID- 29939450
TI - A Simple, Broad-Scope Nickel(0) Precatalyst System for the Direct Amination of
Allyl Alcohols.
AB - The preparation of allylic amines is traditionally accomplished by reactions of
amines with reactive electrophiles, such as allylic halides, sulfonates, or
oxyphosphonium species; such methods involve hazardous reagents, generate
stoichiometric waste streams, and often suffer from side reactions (such as
overalkylation). We report here the first broad-scope nickel-catalysed direct
amination of allyl alcohols: An inexpensive NiII /Zn couple enables the
allylation of primary, secondary, and electron-deficient amines without the need
for glove-box techniques. Under mild conditions, primary and secondary aliphatic
amines react smoothly with a range of allyl alcohols, giving secondary and
tertiary amines efficiently. This "totally catalytic" method can also be applied
to electron-deficient nitrogen nucleophiles; the practicality of the process was
demonstrated in an efficient, gram-scale preparation of the calcium antagonist
drug substance flunarizine (Sibelium(r)).
PMID- 29939451
TI - Engineered nanoparticles interact with nutrients to intensify eutrophication in a
wetland ecosystem experiment.
AB - Despite the rapid rise in diversity and quantities of engineered nanomaterials
produced, the impacts of these emerging contaminants on the structure and
function of ecosystems have received little attention from ecologists. Moreover,
little is known about how manufactured nanomaterials may interact with nutrient
pollution in altering ecosystem productivity, despite the recognition that
eutrophication is the primary water quality issue in freshwater ecosystems
worldwide. In this study, we asked two main questions: (1) To what extent do
manufactured nanoparticles affect the biomass and productivity of primary
producers in wetland ecosystems? (2) How are these impacts mediated by nutrient
pollution? To address these questions, we examined the impacts of a citrate
coated gold nanoparticle (AuNPs) and of a commercial pesticide containing Cu(OH)2
nanoparticles (CuNPs) on aquatic primary producers under both ambient and
enriched nutrient conditions. Wetland mesocosms were exposed repeatedly with low
concentrations of nanoparticles and nutrients over the course of a 9-month
experiment in an effort to replicate realistic field exposure scenarios. In the
absence of nutrient enrichment, there were no persistent effects of AuNPs or
CuNPs on primary producers or ecosystem productivity. However, when combined with
nutrient enrichment, both NPs intensified eutrophication. When either of these
NPs were added in combination with nutrients, algal blooms persisted for >50 d
longer than in the nutrient-only treatment. In the AuNP treatment, this shift
from clear waters to turbid waters led to large declines in both macrophyte
growth and rates of ecosystem gross primary productivity (average reduction of
52% +/- 6% and 92% +/- 5%, respectively) during the summer. Our results suggest
that nutrient status greatly influences the ecosystem-scale impact of two
emerging contaminants and that synthetic chemicals may be playing an under
appreciated role in the global trends of increasing eutrophication. We provide
evidence here that chronic exposure to Au and Cu(OH)2 nanoparticles at low
concentrations can intensify eutrophication of wetlands and promote the
occurrence of algal blooms.
PMID- 29939452
TI - Waste to Chemicals for a Circular Economy.
AB - The implementation of a circular economy is a fundamental step to create a
greater and more sustainable future for a better use of resources and energy.
Wastes and in particular municipal solid waste represent an untapped source of
carbon (and hydrogen) to produce a large range of chemicals from methane to
alcohols (as methanol or ethanol) or urea. The waste to chemical process and
related economics are assessed in this concept article to show the validity of
such solution both from an economic point of view and from an environmental
perspective considering the sensible reduction in greenhouse gas emissions with
respect to conventional production from fossil fuels.
PMID- 29939453
TI - Health and broader community benefit of parkrun-An exploratory qualitative study.
AB - ISSUE ADDRESSED: parkrun is a free, weekly, timed, international mass community 5
km walk/run event. Unlike other paid events, parkrun attracts populations harder
to engage in physical activity (PA) (eg, women, those with overweight/obesity or
illness/injury/disability). This exploratory qualitative study investigated the
individual, social and environmental factors associated with parkrun's broad
appeal in Australia. METHODS: Tasmanian parkrunners who completed a quantitative
survey (2016) were purposively recruited for a 2017 interview study.
Semistructured interviews focused on reasons for parkrun participation. Data
saturation was achieved by the tenth interview. Data were analysed thematically.
RESULTS: Four themes emerged: (a) participation facilitators and barriers; (b) PA
gain and broader community benefit; (c) social connections/networks; and (d)
organisational issues. Appealing characteristics of parkrun included strong
social support, performance gain opportunities, socialising, inclusivity (eg, all
ages/abilities), sense of community, positive atmosphere and accessibility (eg,
no cost and convenience). Some participants reported that parkrun had stimulated
gains in their total PA (not always limited to walking/running) and that parkrun
may also result in other community benefits (eg, supporting local businesses, fee
based running club/event participation and "parkrun tourism"). Most participants
first attended parkrun because of encouragement from their social networks, and
participants subsequently encouraged others to attend. Participants found parkrun
events well organised, but identified some potential threats (eg, local
politics). CONCLUSIONS: Social factors appeared critical in driving initial and
ongoing parkrun participation. parkrun may lead to wider community benefits
beyond that gained through increased individual PA. These findings highlight the
"success factors" driving parkrun participation and provide insights for other
community-based PA promotion activities.
PMID- 29939454
TI - Nanofluidic Ion Transport and Energy Conversion through Ultrathin Free-Standing
Polymeric Carbon Nitride Membranes.
AB - Ions transport through confined space with characteristic dimensions comparable
to the Debye length has many applications, for example, in water desalination,
dialysis, and energy conversion. However, existing 2D/3D smart porous membranes
for ions transport and further applications are fragile, thermolabile, and/or
difficult to scale up, limiting their practical applicability. Now, polymeric
carbon nitride alternatively allows the creation of an ultrathin free-standing
carbon nitride membrane (UFSCNM), which can be fabricated by simple CVD
polymerization and exhibits excellent nanofluidic ion-transport properties. The
surface-charge-governed ion transport also endows such UFSCNMs with the function
of converting salinity gradients into electric energy. With advantages of low
cost, facile fabrication, and the ease of scale up while supporting high ionic
currents, UFSCNM can be considered as an alternative for energy conversion
systems and new ionic devices.
PMID- 29939455
TI - Forest restoration as a strategy to mitigate climate impacts on wildfire,
vegetation, and water in semiarid forests.
AB - Climate change and wildfire are interacting to drive vegetation change and
potentially reduce water quantity and quality in the southwestern United States,
Forest restoration is a management approach that could mitigate some of these
negative outcomes. However, little information exists on how restoration combined
with climate change might influence hydrology across large forest landscapes that
incorporate multiple vegetation types and complex fire regimes. We combined
spatially explicit vegetation and fire modeling with statistical water and
sediment yield models for a large forested landscape (335,000 ha) on the Kaibab
Plateau in northern Arizona, USA. Our objective was to assess the impacts of
climate change and forest restoration on the future fire regime, forest
vegetation, and watershed outputs. Our model results predict that the combination
of climate change and high-severity fire will drive forest turnover, biomass
declines, and compositional change in future forests. Restoration treatments may
reduce the area burned in high-severity fires and reduce conversions from
forested to non-forested conditions. Even though mid-elevation forests are the
targets of restoration, the treatments are expected to delay the decline of high
elevation spruce-fir, aspen, and mixed conifer forests by reducing the occurrence
of high-severity fires that may spread across ecoregions. We estimate that
climate-induced vegetation changes will result in annual runoff declines of up to
10%, while restoration reduced or reversed this decline. The hydrologic model
suggests that mid-elevation forests, which are the targets of restoration
treatments, provide around 80% of runoff in this system and the conservation of
mid- to high-elevation forests types provides the greatest benefit in terms of
water conservation. We also predict that restoration treatments will conserve
water quality by reducing patches of high-severity fire that are associated with
high sediment yield. Restoration treatments are a management strategy that may
reduce undesirable outcomes for multiple ecosystem services.
PMID- 29939456
TI - Bronsted Base Assisted Photoredox Catalysis: Proton Coupled Electron Transfer for
Remote C-C Bond Formation via Amidyl Radicals.
AB - The synthesis of alkyne- and alkene-decorated lactams has been achieved through a
photoredox-initiated radical cascade reaction. The developed Bronsted base
assisted, photoredox-catalyzed, intramolecular 5-exo-trig
cyclization/intermolecular radical addition/elimination reaction provides facile
access to functionalized gamma-lactams, with good functional group tolerance and
high yields.
PMID- 29939457
TI - A Fluorescent G-Quadruplex Sensor for Chemical RNA Copying.
AB - Non-enzymatic RNA replication may have been one of the processes involved in the
appearance of life on Earth. Attempts to recreate this process in a laboratory
setting have not been successful thus far, highlighting a critical need for
finding prebiotic conditions that increase the rate and the yield. Now a highly
parallel assay for template directed RNA synthesis is presented that relies on
the intrinsic fluorescence of a 2-aminopurine modified G-quadruplex. The
application of the assay to examine the combined influence of multiple variables
including pH, divalent metal concentrations and ribonucleotide concentrations on
the copying of RNA sequences is demonstrated. The assay enables a direct survey
of physical and chemical conditions, potentially prebiotic, which could enable
the chemical replication of RNA.
PMID- 29939458
TI - KinITC-One Method Supports both Thermodynamic and Kinetic SARs as Exemplified on
FimH Antagonists.
AB - Affinity data, such as dissociation constants (KD ) or inhibitory concentrations
(IC50 ), are widely used in drug discovery. However, these parameters describe an
equilibrium state, which is often not established in vivo due to pharmacokinetic
effects and they are therefore not necessarily sufficient for evaluating drug
efficacy. More accurate indicators for pharmacological activity are the kinetics
of binding processes, as they shed light on the rate of formation of protein
ligand complexes and their half-life. Nonetheless, although highly desirable for
medicinal chemistry programs, studies on structure-kinetic relationships (SKR)
are still rare. With the recently introduced analytical tool kinITC this
situation may change, since not only thermodynamic but also kinetic information
of the binding process can be deduced from isothermal titration calorimetry (ITC)
experiments. Using kinITC, ITC data of 29 mannosides binding to the bacterial
adhesin FimH were re-analyzed to make their binding kinetics accessible. To
validate these kinetic data, surface plasmon resonance (SPR) experiments were
conducted. The kinetic analysis by kinITC revealed that the nanomolar affinities
of the FimH antagonists arise from both (i) an optimized interaction between
protein and ligand in the bound state (reduced off-rate constant koff ) and (ii)
a stabilization of the transition state or a destabilization of the unbound state
(increased on-rate constant kon ). Based on congeneric ligand modifications and
structural input from co-crystal structures, a strong relationship between the
formed hydrogen-bond network and koff could be concluded, whereas electrostatic
interactions and conformational restrictions upon binding were found to have
mainly an impact on kon .
PMID- 29939459
TI - Chirality Enhancement of Porphyrin Supramolecular Assembly Driven by a Template
Preorganization Effect.
AB - Cationic polylysine promotes, under neutral conditions, the spontaneous
aggregation of opposite charged ZnTPPS in water. Spectroscopic investigations
evidence a different preorganization of ZnTPPS onto the polypeptide matrix
depending on the chain length. Spinodal decomposition theory in confined geometry
is used to model this mechanism by considering the time evolution of a
homogeneous distribution of randomly adsorbed particles (porphyrins) onto a
rodlike polyelectrolyte (polymer) of variable length L.
PMID- 29939460
TI - Habitat-contingent responses to disturbance: impacts of cattle grazing on ant
communities vary with habitat complexity.
AB - Predicting community responses to disturbance is a major challenge for both
ecology and ecosystem management. A particularly challenging issue is that the
same type and intensity of disturbance can have different impacts in different
habitats. We investigate how habitat contingency influences ant community
responses to disturbance in arid Australia, testing the hypothesis that
disturbance has a greater impact in more complex habitats. We also assess the
effectiveness of a highly simplified ant assessment protocol that considers
larger species only. We sampled ants at 46 sites from two habitats (Chandler, low
chenopod shrubland; and mulga, low woodland) with contrasting complexity, using
distance from water as a surrogate for variation in grazing intensity. We
assessed variation in habitat structural variables (basal area of perennial
grass, and cover of herbs, litter, and bare ground) and ant communities in
relation to habitat and distance from water, first using data from the entire ant
community and then for larger ants (>4 mm body length) only. Site species
richness was almost twice as high in mulga, the more structurally complex
habitat, than in Chandler, and ant communities in mulga showed far more variation
in relation to distance from water. Litter cover was the key environmental
variable associated with the interaction between grazing and habitat: it
increased with increasing distance from water in mulga and was virtually absent
from Chandler. Analysis of only larger species revealed the same patterns of
variation in ant abundance, species richness and composition in relation to
habitat and grazing as shown by entire ant communities. Our findings support the
hypothesis that disturbance impacts on faunal communities increase with
increasing habitat complexity. An appreciation of such habitat contingency is
important for a predictive understanding and therefore effective management of
disturbances such as rangeland grazing. Our findings also show that simplified
assessment can provide robust information on the responses of highly diverse ant
communities to disturbance, which enhances their feasibility for use as bio
indicators in land management.
PMID- 29939462
TI - Thinking Outside the Box-Novel Antibacterials To Tackle the Resistance Crisis.
AB - The public view on antibiotics as reliable medicines changed when reports about
"resistant superbugs" appeared in the news. While reasons for this resistance
development are easily spotted, solutions for re-establishing effective
antibiotics are still in their infancy. This Review encompasses several aspects
of the antibiotic development pipeline from very early strategies to mature
drugs. An interdisciplinary overview is given of methods suitable for mining
novel antibiotics and strategies discussed to unravel their modes of action.
Select examples of antibiotics recently identified by using these platforms not
only illustrate the efficiency of these measures, but also highlight promising
clinical candidates with therapeutic potential. Furthermore, the concept of
molecules that disarm pathogens by addressing gatekeepers of virulence will be
covered. The Review concludes with an evaluation of antibacterials currently in
clinical development. Overall, this Review aims to connect select innovative
antimicrobial approaches to stimulate interdisciplinary partnerships between
chemists from academia and industry.
PMID- 29939461
TI - Diversity of hepatitis E virus genotype 3.
AB - Hepatitis E virus genotype 3 (HEV-3) can lead to chronic infection in
immunocompromised patients, and ribavirin is the treatment of choice. Recently,
mutations in the polymerase gene have been associated with ribavirin failure but
their frequency before treatment according to HEV-3 subtypes has not been studied
on a large data set. We used single-molecule real-time sequencing technology to
sequence 115 new complete genomes of HEV-3 infecting French patients. We analyzed
phylogenetic relationships, the length of the polyproline region, and mutations
in the HEV polymerase gene. Eighty-five (74%) were in the clade HEV-3efg, 28
(24%) in HEV-3chi clade, and 2 (2%) in HEV-3ra clade. Using automated
partitioning of maximum likelihood phylogenetic trees, complete genomes were
classified into subtypes. Polyproline region length differs within HEV-3 clades
(from 189 to 315 nt). Investigating mutations in the polymerase gene, distinct
polymorphisms between HEV-3 subtypes were found (G1634R in 95% of HEV-3e, G1634K
in 56% of HEV-3ra, and V1479I in all HEV-3efg, clade HEV-3ra, and HEV-3k
strains). Subtype-specific polymorphisms in the HEV-3 polymerase have been
identified. Our study provides new complete genome sequences of HEV-3 that could
be useful for comparing strains circulating in humans and the animal reservoir.
PMID- 29939463
TI - Self-Assembly of Functional Discrete Three-Dimensional Architectures in Water.
AB - Construction of discrete, self-assembled architectures in water has gained
significant interest in recent years as a wide range of applications arises from
their defined 3D structure. In this review we jointly discuss the efforts of
supramolecular chemists and biotechnologists who previously worked independently,
to tackle discipline-specific challenges associated with construction of
assemblies from synthetic and bio-derived components, respectively. Going
forward, a more interdisciplinary research approach will expedite development of
complexes with real-world applications that exploit the benefits of
compartmentalisation. In support of this, we summarise advances made in the
development of discrete, water-soluble assemblies, with particular focus on their
current and prospective applications. Areas where understanding and methodologies
can be transferred from one sector to the adjacent field are highlighted in
anticipation this will yield advances not possible from either field alone.
PMID- 29939464
TI - Designing Deep-UV Birefringent Crystals by Cation Regulation.
AB - Two new alkaline earth metal fluorooxoborates, CaB4 O6 F2 and SrB4 O6 F2 , have
been synthesized and characterized. The title compounds are isostructural and
crystallize in centrosymmetric space group P1? (No. 2). Structurally, the
fundamental building blocks, B4 O8 F2 groups, are connected by B-O bonds to form
[B4 O6 F2 ]infinity layers, which stack parallelly along the c axis. In addition,
BaB4 O6 F2 , a known fluorooxoborate with different crystal structure, was also
synthesized and characterized for comparison. The cation size influence on the
structure of this MB4 O6 F2 (M=Ca, Sr, Ba) family is discussed in detail. The
diffuse-reflectance spectroscopy measurements indicate that the cutoff edges of
title compounds are below 190 nm. Moreover, first-principle calculation results
demonstrate that MB4 O6 F2 (M=Ca, Sr, Ba) have large birefringence of 0.091,
0.089, and 0.085 at 1064 nm. Both experimental and theoretical studies suggest
that MB4 O6 F2 (M=Ca, Sr, Ba) are promising birefringent materials for deep-UV
applications.
PMID- 29939465
TI - Realizing the Potential of Acetylenedicarboxylate by Functionalization to
Halofumarate in ZrIV Metal-Organic Frameworks.
AB - A strategy was developed to obtain from acetylenedicarboxylic acid either an
acetylenedicarboxylate-based ZrIV metal-organic framework (MOF) with fcu topology
or a halo-functionalized-MOF-801 through in situ ligand hydrohalogenation. The
new materials feature exceptionally high hydrophilicity and CO2 /H2 adsorption
energetics. The acetylenedicarboxylate linker and its functionalizable triple
bond discloses its potential in the engineering of microporous materials with
targeted properties.
PMID- 29939466
TI - Ultrafast Iron-Catalyzed Reduction of Functionalized Ketones: Highly
Enantioselective Synthesis of Halohydrines, Oxaheterocycles, and Aminoalcohols.
AB - A molecularly defined chiral boxmi iron alkyl complex catalyzes the hydroboration
of various functionalized ketones and provides the corresponding chiral
halohydrines, oxaheterocycles (oxiranes, oxetanes, tetrahydrofurans, and
dioxanes) and amino alcohols with excellent enantioselectivities (up to >99 %ee)
and conversion efficiencies at low catalyst loadings (as low as 0.5 mol %).
Turnover frequencies of greater than 40000 h-1 at -30 degrees C highlight the
activity of this earth-abundant metal catalyst which tolerates a large number of
functional groups.
PMID- 29939467
TI - Luminescence from Lanthanide(III) Ions Bound to the Glycocalyx of Chinese Hamster
Ovary Cells.
AB - Lanthanide(III) ions bind to the glycocalyx of Chinese Hamster Ovary (CHO) cells
and give rise to a unique luminescent fingerprint. Following direct excitation of
terbium(III) and europium(III) ions in the visible part of the spectrum, we are
able to collect emission spectra pixel-by-pixel in images of CHO cells. Following
data analysis that removes the background signal, the fine structure of the
europium(III) luminescence indicate that the lanthanide(III) ions are bound to a
single structure of the CHO cell glycocalyx. This was deduced from the fact that
the structure-sensitive emission spectrum of europium is unchanged throughout the
investigated samples.
PMID- 29939468
TI - Precision Switching in a Discrete Supramolecular Assembly: Alkali Metal Ion
Carboxylate Selectivities and the Cationic Hofmeister Effect.
AB - A cavitand host has been shown to switch from a dimeric assembly to a tetrameric
assembly in the presence of cations. Induced by pseudo-specific cation binding
attenuating the net negative charge of each host, switching was shown to be
highly cation selective. Thus, the concentration of cation required to induce
assembly switching ranged from 2 mM in the case of N(n-Bu)4+ to ~80 mM in the
case of Na+ . Overall cation affinity was found to be essentially the reverse of
Collins' law of matching water affinities, which predicts Na+ to have the
strongest affinity for carboxylate groups. Combined with previous data, these
results highlight the point that cation affinity for carboxylates are in large
part dictated by context.
PMID- 29939469
TI - Cobalt-Catalyzed Cross-Couplings between Alkenyl Acetates and Aryl or Alkenyl
Zinc Pivalates.
AB - CoBr2 (5 mol %) in the presence of 2,2'-bipyridyl (5 mol %) enables electrophilic
alkenylations between easily accessible alkenyl acetates or tosylates and various
functionalized aryl zinc pivalates at ambient temperature. This cobalt-catalyzed
process was further applicable to alkenyl zinc pivalates to provide substituted
1,3-dienes.
PMID- 29939470
TI - Diet Enriched with Olive Oil Attenuates Placental Dysfunction in Rats with
Gestational Diabetes Induced by Intrauterine Programming.
AB - SCOPE: Offspring from rats with mild diabetes develop gestational diabetes
mellitus (GDM). We tested the hypothesis that an olive oil-supplemented diet
attenuates placental oxidative stress/inflammation, activation of mTOR signaling,
and inhibition of peroxisome proliferator-activated receptor gamma (PPARgamma)
and fetal overgrowth in GDM offspring from mild diabetic rats. METHODS AND
RESULTS: Female offspring from rats with mild diabetes (group that developed GDM)
and controls were fed with either a standard diet or a 6% olive oil-supplemented
diet during pregnancy. On day 21 of pregnancy, plasma glucose levels in mothers
and fetuses were increased in the GDM group independently of the diet. Fetal
overgrowth and activation of placental mTOR signaling were partially prevented in
the olive oil-treated GDM group. Placental PPARgamma protein expression was
decreased in GDM rats, independently of the diet. However, increases in placental
lipoperoxidation, connective tissue growth factor, and matrix metalloproteinase 2
levels were prevented by the olive oil-enriched diet. CONCLUSION: Diets enriched
with olive oil attenuate placental dysfunction and fetal overgrowth in rats with
GDM induced by intrauterine programming.
PMID- 29939471
TI - Maintaining T cell tolerance of alloantigens: Lessons from animal studies.
AB - Achieving host immune tolerance of allogeneic transplants represents the ultimate
challenge in clinical transplantation. It has become clear that different cells
and mechanisms participate in acquisition versus maintenance of allograft
tolerance. Indeed, manipulations which prevent tolerance induction often fail to
abrogate tolerance once it has been established. Hence, elucidation of the
immunological mechanisms underlying maintenance of T cell tolerance to
alloantigens is essential for the development of novel interventions that
preserve a robust and long lasting state of allograft tolerance that relies on T
cell deletion in addition to intra-graft suppression of inflammatory immune
responses. In this review, we discuss some essential elements of the mechanisms
involved in the maintenance of naturally occurring or experimentally induced
allograft tolerance, including the newly described role of antigen cross-dressing
mediated by extracellular vesicles.
PMID- 29939472
TI - SnO2 : A Wonderful Electron Transport Layer for Perovskite Solar Cells.
AB - The highest power conversion efficiency of perovskite solar cells is beyond 22%.
Charge transport layers are found to be critical for device performance and
stability. A traditional electron transport layer (ETL), such as TiO2 , is not
very efficient for charge extraction at the interface, especially in planar
structure. In addition, the devices using TiO2 suffer from serious degradation
under ultraviolet illumination. SnO2 owns a better band alignment with the
perovskite absorption layer and high electron mobility, which is helpful for
electron extraction. In this Review, recent progresses in efficient and stable
perovskite solar cells using SnO2 as ETL are summarized.
PMID- 29939473
TI - Co-production: Power, problems and possibilities.
PMID- 29939474
TI - Hamsters Are a Better Model System than Rats for Evaluating the
Hypocholesterolemic Efficacy of Potential Probiotic Strains.
AB - SCOPE: Rats and hamsters are the most commonly used animal models for evaluating
the hypocholesterolemic activity of potential probiotic strains, whereas little
or no information has been reported on whether the animal models would affect the
experimental conclusions regarding the hypocholesterolemic efficacy of the
strains. METHODS AND RESULTS: Both high-cholesterol-fed rats and hamsters were
intragastrically administered viable cells of bile salt hydrolase-active
Lactobacillus acidophilus K16 once daily (1 * 1010 CFU per kg body weight) for 28
d. It was found that the strain did not significantly (p > 0.05) affect the serum
and hepatic cholesterol levels in rats, whereas it significantly decreased (p <
0.01 or p < 0.001) the serum total and non-HDL-cholesterol as well as hepatic
free, esterified, and total cholesterol levels in hamsters by 29.6%, 38.8%,
15.8%, 36.2%, and 34.0%, respectively. CONCLUSION: These data suggest that the
hypocholesterolemic efficacy of L. acidophilus K16 is substantially different
between high-cholesterol-fed hamsters and rats and that hamsters are a better
model system than rats for evaluating the hypocholesterolemic efficacy of
potential probiotic strains due to their similarity to humans in biliary bile
acid composition, including types of bile acids and their conjugation form.
PMID- 29939475
TI - Reconstructing phylogeny from reduced-representation genome sequencing data
without assembly or alignment.
AB - Reduced-representation genome sequencing such as RADseq aids the analysis of
genomes by reducing the quantity of data, thereby lowering both sequencing costs
and computational burdens. RADseq was initially designed for studying genetic
variation across genomes at the population level, but has also proved to be
suitable for interspecific phylogeny reconstruction. RADseq data pose challenges
for standard phylogenomic methods, however, due to incomplete coverage of the
genome and large amounts of missing data. Alignment-free methods are both
efficient and accurate for phylogenetic reconstructions with whole genomes and
are especially practical for nonmodel organisms; nonetheless, alignment-free
methods have not been applied with reduced genome sequencing data. Here, we test
a full-genome assembly- and alignment-free method, AAF, in application to RADseq
data and propose two procedures for reads selection to remove reads from
restriction sites that were not found in taxa being compared. We validate these
methods using both simulations and real data sets. Reads selection improved the
accuracy of phylogenetic construction in every simulated scenario and the two
real data sets, making AAF as good or better than a comparable alignment-based
method, even though AAF had much lower computational burdens. We also
investigated the sources of missing data in RADseq and their effects on phylogeny
reconstruction using AAF. The AAF pipeline modified for RADseq or other reduced
representation sequencing data, phyloRAD, is available on github
(https://github.com/fanhuan/phyloRAD).
PMID- 29939476
TI - One Second Formation of Large Area Graphene on a Conical Tip Surface via Direct
Transformation of Surface Carbide.
AB - Graphene functionalized nanotips are expected to possess promising potential for
various applications based on the outstanding electrical and mechanical
properties of graphene. However, current methods, usually requiring a high growth
temperature and identical crystal surface to match graphene lattice, are suitable
for graphene formation on a flat surface. It remains a big challenge to grow
graphene on a nanosized convex surface and fabricate functionalized nanotips with
high quality graphene at the apex. In this work, a novel ultrafast annealing
method is developed for growing large area graphene on Ni nanotips within 1-2 s.
Few layered or multiple layered graphene is presented on the apex or sidewall of
the conical tip surface. Direct experimental evidences support that thus-produced
graphene is formed via the direct conversion of nickel carbide at the outer
surface under the instantaneous high temperature, which is different from the
conventional segregation mechanism. This newly developed ultrafast method
provides a new route to produce graphene efficiently and economically, promising
for both convex surfaces and flat substrates. Moreover, the graphene
functionalized nanotips exhibit a great potential for nanoelectrical measurements
and conductive scanning probe microscopy (SPM) applications.
PMID- 29939477
TI - Surface property alterations and osteoblast attachment to contaminated titanium
surfaces after different surface treatments: An in vitro study.
AB - BACKGROUND: Studies have reported a high prevalence of peri-implantitis. The
etiology of peri-implantitis remains unclear and no available treatments result
in total resolution of established peri-implantitis. PURPOSE: To investigate the
factors that interfere with osteoblast adhesion to contaminated titanium surfaces
after different surface treatments. MATERIALS AND METHODS: Grade 4 titanium discs
were randomly divided into 5 groups and each group was divided into 2 subgroups,
with one contaminated with Aggregatibacter actinomycetemcomitans (A.
actinomycetemcomitans), and the other contaminated with Porphyromonas gingivalis
(P. gingivalis). Group 1 did not receive bacterial inoculation or surface
debridement and served as a control. Group 2 received A. actinomycetemcomitans or
P. gingivalis inoculation, separately. Group 3 received bacterial inoculation and
titanium curette debridement, followed by normal saline irrigation. Group 4
received bacterial inoculation, curette debridement, normal saline irrigation,
and ultrasonication. Group 5 received bacterial inoculation, curette debridement,
normal saline irrigation, and placement in 0.12% chlorhexidine. After various
surface treatments, the surface roughness and hydrophilicity of the titanium
surface were measured, the number of adhered osteoblast cells was calculated, and
the amount of residual lipopolysaccharide (LPS) was quantified. RESULTS: A.
actinomycetemcomitans and P. gingivalis biofilms noticeably reduced surface
hydrophilicity. Groups 3-5 showed decreased hydrophilicity and fewer adhered
osteoblast cells compared with the control group. Although ultrasonication was
more effective in removing LPS than curette debridement and chlorhexidine, cell
adhesion was not as high as with clean titanium discs. CONCLUSIONS: The non
surgical treatment used in this study was not effective in removing LPS from
titanium surfaces and increasing osteoblast adhesion. A more effective method to
remove LPS completely is required to enhance the treatment outcome of peri
implantitis.
PMID- 29939478
TI - Muscle PGC-1alpha in exercise and fasting-induced regulation of hepatic UPR in
mice.
AB - AIM: To provide a detailed time course of hepatic autophagy and all UPR branches
in response to an acute bout of exercise and 24 hours of fasting and test the
hypothesis that muscle-specific PGC-1alpha overexpression dampens the UPR and
autophagy responses to these metabolic challenges. METHODS: Muscle-specific PGC
1alpha overexpression (TG) and wild-type (WT) mice (a) performed a single bout of
exercise, where the liver was obtained immediately after exercise, 2, 6 or 10
hours into recovery as well as from resting mice or (b) fasted for 24 hours or
remained fed and the liver was obtained. RESULTS: In both genotypes, hepatic PERK
and eIF2alpha phosphorylation increased immediately after exercise, with no
change in IRE1alpha phosphorylation and cleaved ATF6 protein. Fasting decreased
PERK, eIF2alpha and IRE1alpha phosphorylation as well as increased cleaved ATF6
protein in both genotypes. Hepatic p62 was unchanged, while LC3II/LC3I ratio
increased immediately after exercise and LC3II protein increased in response to
fasting in both genotypes. TG mice had lower eIF2alpha phosphorylation after
exercise, a blunted fasting-induced CHOP and HSP72 mRNA response and in fasted
mice lower GADD34 and BiP mRNA as well as FAS protein in the liver than WT mice.
CONCLUSION: This study provides for the first time evidence for transient pathway
specific activation of hepatic UPR and increase in markers of autophagy in the
liver with acute exercise. On the other hand, fasting both increased and
decreased UPR branches and seemed to increase autophagy. In addition, muscle PGC
1alpha seemed to dampen some of these responses.
PMID- 29939479
TI - Tailoring Thin-Film Piezoelectrics for Crash Sensing.
AB - Crash sensing and its assessment play a pivotal role in autonomous vehicles for
preventing fatal casualties. Existing crash sensors are severely bottlenecked by
sluggish response time, rigid mechanical components, and space constraints.
Miniaturized sensors embedded with custom-tailored nanomaterials upholds
potential to overcome these limitations. In this article, piezoelectric Zinc
Oxide thin film as a crash sensing layer is integrated onto a flexible metal
alloy cantilever. Material characterization studies are conducted to confirm
piezoelectric property of sputtered ZnO film. The piezoelectric d 31 coefficient
value of ZnO film was 7.2 pm V-1 . The ZnO sensing element is firmly mounted on a
scaled car model and used in a crash sensing experimental set-up. A comprehensive
theoretical analysis for two different real scenarios (nearly elastic and nearly
inelastic collision) of crash events followed by experimental study is discussed.
The crash sensor's output exhibits a linear relationship with magnitude of impact
forces experienced at crash events. The response time of ZnO crash sensor is 18.2
ms, and it exhibits a sensitivity of 28.7 mV N-1 . The developed crash sensor has
potential to replace bulk material sensors owing to its faster response time,
high sensitivity, and compactness as the demand for crash sensors in next
generation automobile industries is progressively growing.
PMID- 29939480
TI - HHV-6 and septic shock: Tenuous proof of causation.
PMID- 29939481
TI - Cell- and Tissue-Based Proteome Profiling and Bioimaging with Probes Derived from
a Potent AXL Kinase Inhibitor.
AB - AXL has been defined as a novel target for cancer therapeutics. However, only a
few potent and selective inhibitors targeting AXL are available to date.
Recently, our group has developed a lead compound, 9im, capable of displaying
potent and specific inhibition of AXL. To further identify the cellular on/off
targets, in this study, competitive affinity-based proteome profiling was carried
out, leading to the discovery of several unknown cellular targets such as BCAP31,
LPCAT3, POR, TM9SF3, SCCPDH and CANX. In addition, trans-cyclooctene (TCO) and
acedan-containing probes were developed to image the binding between 9im and its
target proteins inside live cells and tumor tissues. These probes would be useful
tools in the detection of AXL in various biosystems.
PMID- 29939482
TI - A Platinum(II) Complex of Heptamethine Cyanine for Photoenhanced Cytotoxicity and
Cellular Imaging in Near-IR Light.
AB - Controlled generation of cytotoxic agents with near-IR light is a current focus
of photoactivated cancer therapy, including that involving cytotoxic platinum
species. A heptamethine cyanine scaffolded PtII complex, IR797-Platin exhibits
unprecedented Pt-O bond scission and enhancement in DNA platination in near-IR
light. This complex also displayed significant singlet oxygen quantum yield
thereby qualifying as a near-IR photodynamic therapeutic agent. The complex
showed 30-60 fold enhancement of cytotoxicity in near-IR light in various cancer
cell lines. The cellular imaging properties were also leveraged to observe its
significant co-localization in cytoplasmic organelles. This is the first
demonstration of a near-IR light-initiated therapy involving the cytotoxic
effects of both active cisplatin and singlet oxygen.
PMID- 29939483
TI - Same-day antiretroviral therapy (ART) initiation in pregnancy is not associated
with viral suppression or engagement in care: A cohort study.
AB - INTRODUCTION: Many prevention of mother-to-child HIV transmission programmes
across Africa initiate HIV-infected (HIV positive) pregnant women on lifelong
antiretroviral therapy (ART) on the first day of antenatal care ("same-day"
initiation). However, there are concerns that same-day initiation may limit
patient preparation before starting ART and contribute to subsequent non
adherence, disengagement from care and raised viral load. We examined if same-day
initiation was associated with viral suppression and engagement in care during
pregnancy. METHODS: Consecutive ART-eligible pregnant women making their first
antenatal care (ANC) visit at a primary care facility in Cape Town, South Africa
were enrolled into a prospective cohort between March 2013 and June 2014. Before
July 2013, ART eligibility was based on CD4 cell count <=350 cells/MUL ("Option
A"), with a 1 to 2 week delay from the first ANC visit to ART initiation for
patient preparation; thereafter all women were eligible regardless of CD4 cell
count ("Option B+") and offered ART on the same day as first ANC visit. Women
were followed with viral load testing conducted separately from routine ART
services, and engagement in ART services was measured using routinely collected
clinic, pharmacy and laboratory records through 12 months postpartum. RESULTS:
Among 628 HIV-positive women (median age, 28 years; median gestation at ART
start, 21 weeks; 55% newly diagnosed with HIV), 73% initiated ART same-day; this
proportion was higher under Option B+ versus Option A (85% vs. 20%). Levels of
viral suppression (viral load <50 copies/mL) at delivery (74% vs. 82%) and 12
months postpartum (74% vs. 71%) were similar under same-day versus delayed
initiation respectively. Findings were consistent when viral suppression was
defined at <1000 copies/mL, after adjustment for demographic/clinical measures
and across subgroups of age, CD4 and timing of HIV diagnosis. Time to first viral
rebound following initial suppression did not differ by timing of ART initiation
nor did engagement in care through 12 months postpartum (same-day = 73%, delayed
= 73%, p = 0.910). CONCLUSIONS: These data suggest that same-day ART initiation
during pregnancy is not associated with lower levels of engagement in care or
viral suppression through 12 months post-delivery in this setting, providing
reassurance to ART programmes implementing Option B+.
PMID- 29939484
TI - Enhanced Cytosolic Delivery and Release of CRISPR/Cas9 by Black Phosphorus
Nanosheets for Genome Editing.
AB - A biodegradable two-dimensional (2D) delivery platform based on loading black
phosphorus nanosheets (BPs) with Cas9 ribonucleoprotein engineered with three
nuclear localization signals (NLSs) at C terminus (Cas9N3) is successfully
established. The Cas9N3-BPs enter cells effectively via membrane penetration and
endocytosis pathways, followed by a BPs biodegradation-associated endosomal
escape and cytosolic releases of the loaded Cas9N3 complexes. The Cas9N3-BPs thus
provide efficient genome editing and gene silencing in vitro and in vivo at a
relatively low dose as compared with other nanoparticle-based delivery platforms.
This biodegradable 2D delivery platform offers a versatile cytosolic delivery
approach for CRISPR/Cas9 ribonucleoprotein and other bioactive macromolecules for
biomedical applications.
PMID- 29939485
TI - Covalent Chemical Cochaperones of the p300/CBP GACKIX Domain.
AB - The GACKIX activator binding domain has been a compelling target for small
molecule probe discovery because of the central role of activator-GACKIX
complexes in diseases ranging from leukemia to memory disorders. Additionally,
GACKIX is an ideal model to dissect the context-dependent function of activator
coactivator complexes. However, the dynamic and transient protein-protein
interactions (PPIs) formed by GACKIX are difficult targets for small molecules.
An additional complication is that activator-binding motifs, such as GACKIX, are
found in multiple coactivators, making specificity difficult to attain. In this
study, we demonstrate that the strategy of tethering can be used to rapidly
discover highly specific covalent modulators of the dynamic PPIs between
activators and coactivators. These serve as both ortho- and allosteric
modulators, enabling the tunable assembly or disassembly of the activator
coactivator complexes formed between the KIX domain and its cognate activator
binding partners MLL and CREB. The molecules maintain their function and
selectivity, even in human cell lysates and in bacterial cells, and thus, will
ultimately be highly useful probes for cellular studies.
PMID- 29939486
TI - The Red-/Green-Switching GAF3 of Cyanobacteriochrome Slr1393 from Synechocystis
sp. PCC6803 Regulates the Activity of an Adenylyl Cyclase.
AB - Cyanobacteriochromes (CBCRs) are photoreceptors in cyanobacteria that present a
bilin chromophore-binding GAF domain as a photochromic element to control the
activity of a downstream enzyme or regulator. CBCR Slr1393 from Synechocystis PCC
6803 carries three GAF domains, but only the third one binds phycocyanobilin
covalently. Slr1393 shows photochromicity between red and green absorbing states
and regulates a C-terminally located histidine kinase. In this work, we fused
this third GAF domain to an adenylyl cyclase (AC) from Microcoleus chthonoplastes
PCC7420 that in its genuine form is under blue-light control from a LOV domain. A
series of RGS-AC variants were constructed with various lengths of the linkers
between RGS and AC. Assays in vitro and in living Escherichia coli cells (AC
deletion mutant) demonstrated that the activity of AC was light regulated,
namely, the red-light-converted form of RGSDelta14-Delta4AC (in vitro) was about
three times more active than the green-light-converted form. Expression of the
fusion protein RGSDelta14-Delta4AC in vivo again showed highest light regulation
with at least threefold amplification of the AC function. In some experiments,
even tenfold higher activity was observed, which indicated that the protein, if
expressed under in vivo conditions, was part of the E. coli physiological
conditions and thereby subjected to more complex and variable regulation through
other E. coli inherent factors.
PMID- 29939487
TI - Amiloride resolves resistant edema and hypertension in a patient with nephrotic
syndrome; a case report.
AB - Sodium and fluid retention is a hallmark and a therapeutic challenge of the
nephrotic syndrome (NS). Studies support the "overfill" theory of NS with
pathophysiological proteolytic activation of the epithelial sodium channel (ENaC)
which explains the common observation of suppressed renin -angiotensin system and
poor therapeutic response to ACE inhibitors. Blockade of ENaC by the diuretic
amiloride would be a rational intervention compared to the traditionally used
loop diuretics. We describe a 38-year-old male patient with type1 diabetes who
developed severe hypertension (200/140 mmHg), progressive edema (of at least 10
L), and overt proteinuria (18.5 g/24 h), despite combined administration of five
antihypertensive drugs. Addition of amiloride (5 mg/day) to treatment resulted in
resolution of edema, weight loss of 7 kg, reduction in blood pressure (150/100
125/81 mmHg), increased 24 h urinary sodium excretion (127-165 mmol/day),
decreased eGFR (41-29 mL/min), and increased plasma potassium concentration (4.6
7.8 mmol/L). Blocking of ENaC mobilizes nephrotic edema and lowers blood pressure
in NS. However, acute kidney injury and dangerous hyperkalemia is a potential
risk if amiloride is added to multiple other antihypertensive medications as ACEi
and spironolactone. The findings support that ENaC is active in NS and is a
relevant target in adult NS patients.
PMID- 29939489
TI - When human intelligence meets artificial intelligence.
PMID- 29939488
TI - Prevention paradox: Medical students are less inclined to prescribe HIV pre
exposure prophylaxis for patients in highest need.
AB - INTRODUCTION: Despite healthcare providers' growing awareness of pre-exposure
prophylaxis (PrEP), prescription rates remain low. PrEP is an efficacious HIV
prevention strategy recommended for use with condoms but still protective in
their absence. Concern about the impact of PrEP on condom use and other risk
behaviour is, nonetheless, among the barriers to prescription commonly reported.
To understand the implications of this concern for PrEP access, we examined how
medical students' willingness to prescribe PrEP varied by patients' condom use
and partnering practices. We also assessed the perceived acceptability of various
reasons for condom discontinuation with PrEP. METHODS: An online survey was
distributed to 854 medical students in the Northeastern US in 2015. Participants
(n = 111) were surveyed about their willingness to prescribe PrEP for each of six
male patients who systematically differed in their reported condom use (sustained
use, sustained nonuse, or discontinuation with PrEP) and partnering practices
(single male partner with untreated HIV or multiple male partners of unknown HIV
status). Participants also reported perceived acceptability of four reasons for
condom discontinuation: pleasure, sexual functioning, intimacy, and conception.
RESULTS: Willingness to prescribe PrEP was inconsistent with patient risk: When
the patient used condoms and planned to sustain condom use, most participants
were willing to prescribe PrEP - 93% if the patient had a single partner and 86%
if the patient had multiple partners. Fewer were willing to prescribe if the
patient did not use condoms and planned to sustain nonuse (53% and 45%,
respectively) or used condoms but planned to discontinue use (27% and 28%).
Significantly fewer participants were willing to prescribe for a patient with
multiple partners versus a single partner when the patient reported sustained
condom use or sustained condom nonuse. The number of participants who were
willing to prescribe was similarly low for a patient with multiple partners
versus a single partner when the patient reported that he planned to discontinue
condom use. More participants accepted a patient discontinuing condoms for
conception (69%) than for intimacy (23%), pleasure (14%), or sexual functioning
(13%). CONCLUSION: Medical students' clinical judgments were misaligned with
patient risk and suggest misconceptions or personal values may undermine
provision of optimal HIV prevention services.
PMID- 29939490
TI - Older men display elevated levels of senescence-associated exercise-responsive
CD28null angiogenic T cells compared with younger men.
AB - Aging is associated with elevated cardiovascular disease risk. As a result of
aging, endothelial dysfunction develops, partly due to a reduction in vascular
regenerative ability. CD31+ T cells (angiogenic T cells; TANG ) possess highly
angiogenic capabilities; however, these cells are significantly reduced in older
populations. In addition, older populations possess significantly higher
senescent and highly differentiated T-cell levels in circulation, and these are
reported to be highly exercise responsive. We investigated whether older adults
display greater levels of circulating senescent (CD28null ) TANG cells and
whether these cells were more exercise responsive than CD28+ TANG cells. Young
(18-25 years; n = 9) and older (60-75 years; n = 10) healthy men undertook a 30
min cycling bout at 70% VO2 peak, with circulating TANG cells (CD3+ CD31+
CD28+/null ; including CD4+ and CD8+ subsets) measured preexercise, postexercise,
and 1 h post exercise by flow cytometry. Older adults displayed reduced basal
levels of TANG cells (mean +/- SEM: 410 +/- 81 vs. 784 +/- 118 cells.MUL, P =
0.017), despite a greater proportion of these cells being CD28null (26.26 +/-
5.08 vs. 13.36 +/- 2.62%, P = 0.044). Exercise significantly increased the
circulating number of TANG cells in both young and older men. However, in older
men alone, exercise preferentially mobilized CD28null CD8+ TANG cells compared
with CD28+ TANG cells (time * phenotype interaction: P = 0.022; Delta74 +/- 29
vs. Delta27 +/- 15 cells.MUL, P = 0.059), with no such difference observed
between these phenotypes in the young population. In conclusion, this is the
first study to demonstrate that despite observing lower circulating numbers of
TANG cells, older adults display greater levels of senescent TANG cells in
comparison with younger individuals, and these cells are more exercise responsive
than CD28+ TANG cells. Lower number of circulating TANG and greater levels of
senescent-associated CD28null TANG may contribute to greater CVD risk with
advancing age.
PMID- 29939491
TI - Behavioral variation in nesting phenology may offset sex-ratio bias in tuatara.
AB - The nest environment for eggs of reptiles has lifelong implications for offspring
performance and success, and, ultimately, for population viability and species
distributions. However, understanding the various abiotic and biotic drivers of
nesting is complex, particularly regarding variation in nesting behavior of
females and consequences for sex ratios in species with temperature-dependent sex
determination (TSD). We investigated how nest construction and nesting phenology
affect the incubation environment of a reptile with TSD, the tuatara (Sphenodon
punctatus), a species that is at risk from climate-mediated male bias in
population sex ratios. Using longitudinal behavioral data, we addressed the
following questions. (1) Does nesting behavior vary with seasonal or location
cues? (2) Does variation in nesting phenology or nest construction affect the
incubation environment? We aimed to investigate whether female tuatara could
modify nesting behavior to respond to novel environments, including a warming
climate, allowing for successful incubation and balanced population sex ratios,
maintaining population viability throughout their historic range. We predicted
that earlier nesting after warm winters increased the likelihood that females
will be produced, despite the sex determining system where males are produced
from warmer temperatures. Further research is needed to understand the extent to
which nesting behavior varies by individual through time, and across the range of
tuatara, and the importance of habitat variability in maintaining production of
females under future climate warming.
PMID- 29939492
TI - Potassium channels contribute to activity-dependent regulation of dendritic
inhibition.
AB - GABAergic inhibition plays a critical role in the regulation of neuronal
activity. In the neocortex, inhibitory interneurons that target the dendrites of
pyramidal cells influence both electrical and biochemical postsynaptic signaling.
Voltage-gated ion channels strongly shape dendritic excitability and the
integration of excitatory inputs, but their contribution to GABAergic signaling
is less well understood. By combining 2-photon calcium imaging and focal GABA
uncaging, we show that voltage-gated potassium channels normally suppress the
GABAergic inhibition of calcium signals evoked by back-propagating action
potentials in dendritic spines and shafts of cortical pyramidal neurons.
Moreover, the voltage-dependent inactivation of these channels leads to
enhancement of dendritic calcium inhibition following somatic spiking.
Computational modeling reveals that the enhancement of calcium inhibition
involves an increase in action potential depolarization coupled with the
nonlinear relationship between membrane voltage and calcium channel activation.
Overall, our findings highlight the interaction between intrinsic and synaptic
properties and reveal a novel mechanism for the activity-dependent regulation of
GABAergic inhibition.
PMID- 29939493
TI - A three-dimensional (3D) two-way coupled fluid-structure interaction (FSI) study
of peristaltic flow in obstructed ureters.
AB - Obstruction in the ureter flow path is one of the most common problems in urinary
related diseases. As the ureter transports the urine using the expansion bolus
created by the peristaltic pulses, an obstruction in its path can cause unwanted
backflow and can also result in damage to the wall. But in order to understand
this further, and specifically to quantify and parametrize the effect of the
obstruction in the ureter, a detailed study investigating various level of
obstructions in peristaltic ureter flow is necessary. In the current study, full
3D numerical simulations of peristalsis in an obstructed ureter are carried out
using a finite element solver along with a two-way coupling between the fluid and
structural domain with the arbitrary Eulerian-Lagrangian method. Analysis of the
results shows that the larger the obstruction, the higher the wall shear stress
and pressure gradient in the fluid. In addition, the amount of backflow increases
with increase in the obstruction.
PMID- 29939494
TI - Activation of the beta-common receptor by erythropoietin impairs acetylcholine
mediated vasodilation in mouse mesenteric arterioles.
AB - Clinically, erythropoietin (EPO) is known to increase systemic vascular
resistance and arterial blood pressure. However, EPO stimulates the production of
the potent vasodilator, nitric oxide (NO), in culture endothelial cells. The
mechanism by which EPO causes vasoconstriction despite stimulating NO production
may be dependent on its ability to activate two receptor complexes, the
homodimeric EPO (EPOR2 ) and the heterodimeric EPOR/beta-common receptor
(betaCR). The purpose of this study was to investigate the contribution of each
receptor to the vasoactive properties of EPO. First-order, mesenteric arteries
were isolated from 16-week-old male C57BL/6 mice, and arterial function was
studied in pressure arteriographs. To determine the contribution of each receptor
complex, EPO-stimulating peptide (ESP), which binds and activates the
heterodimeric EPOR/betaCR complex, and EPO, which activates both receptors, were
added to the arteriograph chamber 20 min prior to evaluation of endothelium
dependent (acetylcholine, bradykinin, A23187) and endothelium-independent (sodium
nitroprusside) vasodilator responses. Only ACh-induced vasodilation was impaired
in arteries pretreated with EPO or ESP. EPO and ESP pretreatment abolished ACh
induced vasodilation by 100% and 60%, respectively. EPO and ESP did not affect
endothelium-independent vasodilation by SNP. Additionally, a novel betaCR
inhibitory peptide (betaIP), which was computationally developed, prevented the
impairment of acetylcholine-induced vasodilation by EPO and ESP, further
implicating the EPOR/betaCR complex. Last, pretreatment with either EPO or ESP
did not affect vasoconstriction by phenylephrine and KCl. Taken together, these
findings suggest that acute activation of the heterodimeric EPOR/betaCR in
endothelial cells leads to a selective impairment of ACh-mediated vasodilator
response in mouse mesenteric resistance arteries.
PMID- 29939495
TI - Identification of Comprehensive Metabotypes Associated with Cardiometabolic
Diseases in the Population-Based KORA Study.
AB - SCOPE: "Metabotyping" describes the grouping of metabolically similar
individuals. We aimed to identify valid metabotypes in a large cohort for
targeted dietary intervention, for example, for disease prevention. METHODS AND
RESULTS: We grouped 1729 adults aged 32-77 years of the German population-based
KORA F4 study (2006-2008) using k-means cluster analysis based on 34 biochemical
and anthropometric parameters. We identified three metabolically distinct
clusters showing significantly different biochemical parameter concentrations.
Cardiometabolic disease status was determined at baseline in the F4 study and at
the 7 year follow-up termed FF4 (2013/2014) to compare disease prevalence and
incidence between clusters. Cluster 3 showed the most unfavorable marker profile
with the highest prevalence of cardiometabolic diseases. Also, disease incidence
was higher in cluster 3 compared to clusters 2 and 1, respectively, for
hypertension (41.2%/25.3%/18.2%), type 2 diabetes (28.3%/5.1%/2.0%),
hyperuricemia/gout (10.8%/2.3%/0.7%), dyslipidemia (19.2%/18.3%/5.6%), all
metabolic (54.5%/36.8%/19.7%), and all cardiovascular (6.3%/5.5%/2.3%) diseases
together. CONCLUSION: Cluster analysis based on an extensive set of biochemical
and anthropometric parameters allows the identification of comprehensive
metabotypes that were distinctly different in cardiometabolic disease occurrence.
As a next step, targeted dietary strategies should be developed with the goal of
preventing diseases, especially in cluster 3.
PMID- 29939496
TI - Human tissue kallikrein 1 ameliorates erectile function via modulation of
macroautophagy in aged transgenic rats.
AB - Previously, we have demonstrated that human tissue kallikrein 1 (hKLK1) improves
age-related erectile dysfunction (ED). Autophagy has been implicated in age
related diseases, including ED. However, the molecular mechanisms underlying
hKLK1-mediated amelioration of age-related ED via regulation of autophagy remains
unknown. To explore the potential mechanism, male wild-type Sprague-Dawley rats
(WTR) and transgenic rats harboring human KLK1 (TGR) were bred till 4 or 18
months of age and divided into three groups: young WTR (yWTR) as the control
group, aged WTR (aWTR) group, and aged TGR (aTGR) group. The erectile function of
each rat was evaluated using cavernous nerve electrostimulation. The ratio of
intracavernous pressure/mean arterial pressure (ICP/MAP) and total ICP were also
measured. Western blotting, immunohistochemistry, and transmission electron
microscopy were performed to detect the levels of autophagy. The expression
levels of related signaling pathways were determined by western blotting and
immunohistochemistry. We found that hKLK1 improved the impaired erectile function
of aged rats. Compared to the yWTR and aTGR groups, the aWTR group showed reduced
smooth muscle/collagen ratio, fewer autophagosomes, and lower expression of
Beclin 1 and LC3-II, which indicate impaired smooth muscle function and low level
of autophagy in the smooth muscle cells. Moreover, the PI3K/Akt/mTOR signaling
pathway, which is considered to be a negative regulator of autophagy, was
upregulated in the aWTR group. hKLK1 may partially restore erectile function in
aged transgenic rats by upregulating protective autophagy via the PI3K/Akt/mTOR
pathway. These observations indicate that hKLK1 is a potential gene therapy
candidate for age-related ED.
PMID- 29939497
TI - Aromatherapy: Activating olfactory calcium-sensing receptors impairs renal
hemodynamics via sympathetic nerve-mediated vasoconstriction.
AB - AIM: This study determines whether the activation of olfactory calcium-sensing
receptor initiates a sympathetic activation-dependent neurovascular reflex
subsequently contributing to renal hemodynamic depression. METHODS:
Immunohistochemistry and nose-loading calcium-sensitive dye were used to explore
the location and function of calcium-sensing receptor on the olfactory sensory
neuron. The renal sympathetic nervous activity, renal hemodynamics and the
microcirculation of kidney, liver and intestine were evaluated after liquid-phase
intranasal administrations of saline, lidocaine, calcium-sensing receptor
agonists and antagonist in sham and bilateral renal denervated rats. Real-time
renal glomerular filtration rate was measured by a magnetic resonance renography.
RESULTS: Calcium-sensing receptors were expressed on the cilia the olfactory
sensory neuron and their activation depolarized olfactory sensory neuron and
induced the calcium influx in the terminal side on olfactory glomeruli.
Activating olfactory calcium-sensing receptors significantly increased arterial
blood pressure and renal sympathetic nervous activities and subsequently
decreased renal blood flow, renal, hepatic and enteral microcirculation.
Cotreatments with calcium-sensing receptor antagonist or lidocaine inhibited
these physiological alterations. The renal hemodynamic depressions by olfactory
calcium-sensing receptor activation were significantly blocked by bilateral renal
denervation. The intranasal manganese administration decreased the glomerular
filtration rate. CONCLUSION: Calcium-sensing receptor acts as a functional
chemosensory receptor on olfactory sensory neuron, and its activation causes the
global sympathetic enhancement contributing to systematic vasoconstriction and
subsequently depresses renal blood flow and glomerular filtration rate. These
data implicate a possibly clinical aspect that several environmental stimuli may
activate olfactory calcium-sensing receptors to evoke a sympathetic nervous
system-mediated neurovascular reflex to depress renal hemodynamics.
PMID- 29939499
TI - Corrected whole blood biomarkers - the equation of Dill and Costill revisited.
AB - An exercise bout or a dehydration often causes a reduction in plasma volume,
which should be acknowledged when considering the change in biomarkers before and
after the plasma changing event. The classic equation from Dill and Costill
(1974, J. Appl. Physiol., 37, 247-248) for plasma volume shift is usually
utilized in such a case. Although this works well with plasma and serum
biomarkers, we argue in this note that this traditional approach gives misleading
results in the context of whole blood biomarkers, such as lactate, white cells,
and thrombocytes. In this study, we demonstrate that to calculate the change in
the total amount of circulating whole blood biomarker, one should utilize a
formula [Formula: see text] Here Hb and BM are, respectively, the concentrations
for the hemoglobin and for the inspected whole blood biomarker before (pre) and
after (post) the plasma changing incident.
PMID- 29939498
TI - Transcriptome analysis of Porphyromonas gingivalis and Acinetobacter baumannii in
polymicrobial communities.
AB - Acinetobacter baumannii is a nosocomial, opportunistic pathogen that causes
several serious conditions including meningitis, septicemia, endocarditis, and
pneumonia. It can be found in the oral biofilm, which may be a reservoir for
pneumonia and chronic obstructive pulmonary disease. Subgingival colonization by
A. baumannii is associated with chronic and aggressive periodontitis as well as
refractory periodontal disease. Porphyromonas gingivalis, a keystone periodontal
pathogen localized to subgingival plaque, is also implicated in several chronic
conditions including aspiration pneumonia. Although both bacteria are found
together in subgingival plaque and can cause multiple polymicrobial infections,
nothing is known about the interactions between these two important human
pathogens. In this study, we used RNA sequencing to understand the
transcriptional response of both species as they adapt to heterotypic
communities. Among the differentially regulated genes were those encoding a
number of important virulence factors for both species including adhesion,
biofilm formation, and protein secretion. Additionally, the presence of A.
baumannii increased the abundance of P. gingivalis in model dual-species
communities. Collectively these results suggest that both P. gingivalis and A.
baumannii adapt to each other and have synergistic potential for increased
pathogenicity. In identifying the mechanisms that promote pathogenicity and
refractory disease, novel approaches to mitigate polymicrobial synergistic
interactions may be developed to treat or prevent associated diseases.
PMID- 29939500
TI - Cardio-Metabolic Health Venezuelan Study (EVESCAM): Design and Implementation.
AB - The EVESCAM (EstudioVenezolano de Salud Cardio-Metabolica) is the first national,
population survey in Venezuela, designed to examine the prevalence of diabetes
and cardio-metabolic risk factors and its relationship with lifestyle. It is a
cross-sectional, cluster sampling study, which recruited 4454 participants aged
>= 20 years. The data were collected in community health-care centers by trained
health professionals and medical students. Thedata collected from each subject
included, after informed consent, structured questionnaires (clinical,
demographic, physical activity, nutritional and psychological), anthropometric
measurements (weight, height and waist circumference), body fat by bioelectrical
impedance, hand grip, blood pressure, electrocardiogram, and biochemical
measurements (standard 75 g oral glucose tolerance test, total cholesterol, HDL
cholesterol, LDL-cholesterol and triglycerides). The data will be used to
estimate the prevalence of overweight, obesity, prediabetes, diabetes,
hypertension, dyslipidemias, sarcopenia and metabolic syndrome; and to examine
their relationships with lifestyle factors. The risk of coronary heart disease
and impaired glucose regulation will be estimated using the Framingham Coronary
Heart Disease Risk Score and the Latin America adaptation of the Finnish Diabetes
Risk Score (LA-FINDRISC), respectively. These results will guide national
cardiovascular and diabetes prevention strategies, and will be available for
government agencies to help in the implementation of public health policies.
PMID- 29939501
TI - Initial results of a lung cancer screening demonstration project: a local program
evaluation.
AB - OBJECTIVES: To describe participation rates, results, and lessons learned from a
lung cancer screening (LCS) demonstration project. STUDY DESIGN: Prospective
observational study at 1 of 8 centers participating in a national Veterans Health
Administration LCS demonstration project. METHODS: An electronic health record
(EHR) algorithm and tobacco pack-year (TPY) information prompt identified
patients potentially eligible for LCS. LCS invitation was planned to consist of
shared decision-making materials, an invitation letter to call the LCS manager, a
reminder letter, and an outreach phone call for nonresponders. The outreach call
was subsequently dropped due to time constraints on the LCS manager. Lung nodules
and incidental findings on LCS low-dose computed tomography (LDCT) were recorded
in templated radiology reports and tracked with EHR notes. RESULTS: Of 6133
potentially eligible patients, we identified 1388 patients with eligible TPY
information: 918 were invited for LCS and 178 (19%) completed LCS. LCS completion
was more likely in patients in the mailing-plus-call outreach group (phase I)
compared with the mail-only group (phase II) (22% vs 9%; P <.001). Among those
completing an LDCT, 61% had lung nodules requiring follow-up: 43% of the nodules
were less than 4 mm in diameter, 12 patients required further diagnostic
evaluation, and 2 had lung malignancies. There were 179 incidental LDCT findings
in 116 patients, and 20% were clinically significant. CONCLUSIONS: Important
considerations in LCS are accurate identification of eligible patients, balancing
invitation approaches with resource constraints, and establishing standardized
methods for tracking numerous small lung nodules and incidental findings detected
by LDCT.
PMID- 29939502
TI - Prevalence and predictors of hypoglycemia in South Korea.
AB - OBJECTIVES: This study aimed to identify the prevalence and predictors of
hypoglycemia in patients with type 2 diabetes (T2D) using South Korea's
nationwide healthcare database. STUDY DESIGN: Retrospective cohort and nested
case-control analyses were conducted to estimate the prevalence and predictors of
hypoglycemia, respectively. METHODS: A cohort of 2,273,481 patients with T2D was
followed to estimate the 1-year prevalence of hypoglycemia. Total hypoglycemia
was identified using outpatient, inpatient, or emergency department visit data
containing a diagnosis code for hypoglycemia. Severe hypoglycemia was defined as
an event with inpatient admission or emergency care. Within the T2D cohort, cases
with hypoglycemia were identified, and up to 4 controls were randomly selected
after matching by sex, age, and cohort entry date. Possible predictive factors
included insurance type, medical institution type, hypoglycemic history,
antidiabetic drugs, Charlson Comorbidity Index score, and diabetic complications.
We conducted conditional logistic regression analyses to estimate adjusted odds
ratios (aORs) and 95% CIs to identify predictors of hypoglycemia. RESULTS: The
prevalences of total and severe hypoglycemia were 1.38% and 0.96%, respectively.
Those with a history of hypoglycemia had the highest risk for a further
hypoglycemic event (aOR, 16.71; 95% CI, 15.62-17.88). Use of combination therapy
with insulin and sulfonylurea was highly associated with severe hypoglycemia
(aOR, 15.09; 95% CI, 13.60-16.74). Among diabetic complications, the presence of
nephropathy was the greatest predictive factor (aOR, 1.79; 95% CI, 1.73-1.85).
CONCLUSIONS: Patients with a history of hypoglycemia or receiving combined
antidiabetic therapy must be appropriately managed to achieve optimal glycemic
control without significant risk of hypoglycemia.
PMID- 29939503
TI - Physician practice variation under orthopedic bundled payment.
AB - OBJECTIVES: To describe the extent of and longitudinal changes in physician
practice variation with respect to implant costs, institutional postacute care
(PAC) provider utilization, and total episode payments, as well as to evaluate
the association between physician volume and quality and these outcomes. STUDY
DESIGN: Observational study. METHODS: We combined claims and internal hospital
cost data for 34 physicians responsible for 3614 joint replacement episodes under
bundled payment at Baptist Health System (BHS). Multilevel multivariable
generalized linear models were employed and the intraclass correlation (ICC) was
used to quantify between-physician variation. RESULTS: There was significant
between-physician variation in implant costs, institutional PAC provider
utilization, and total episode payments not explained by observable variables (P
<.001 for all). Over 5 years, the ICC decreased from 0.26 to 0.06, 0.15 to 0.13,
and 0.12 to 0.10 for implant costs, institutional PAC provider utilization, and
total episode payments, respectively, but differences were not statistically
significant. Both higher physician case volume and quality were associated with
decreased total episode payments and institutional PAC provider utilization, but
not with changes in implant costs. CONCLUSIONS: Considerable physician practice
variation was observed under bundled payment at BHS and decreased to a greater
degree for implant costs than institutional PAC provider utilization or total
episode payments. Institutional PAC provider utilization and total episode
payments were associated with physician volume and quality. Although some
organizational strategies achieve gains by reducing physician practice variation,
variation reduction is not an absolute requisite for success under bundled
payment.
PMID- 29939504
TI - A longitudinal examination of the asthma medication ratio in children.
AB - OBJECTIVES: The asthma medication ratio (AMR) (number of controller medications /
[number of controller medications + number of rescue medications]) can be
calculated using claims data. This measure has not previously been studied
longitudinally. Our objective is to conduct a longitudinal examination of the AMR
in a large national cohort of children with asthma. STUDY DESIGN: Retrospective
analysis of pharmacy and medical claims data. METHODS: Using 2013-2014
TruvenHealth MarketScan data, we identified children with asthma. Beginning with
the month of first controller claim, we calculated an AMR for each rolling 3
month period and each rolling 6-month period and examined the proportion who had
AMRs classified as low-risk (>=0.5), high-risk (<0.5), and missing for each
period. Using logistic regression, we tested how a rolling AMR predicted a
child's hospitalization or emergency department (ED) visit for asthma. RESULTS:
We identified 197,316 patients aged 2 to 17 years with a claim for a controller.
AMRs were relatively stable over time, with the majority of patients remaining in
the same AMR category through a 12-month period. Using both the rolling 3-month
and 6-month AMRs, a higher proportion of patients with high-risk AMRs (9.6% and
9.5%, respectively) had an ED visit or hospitalization compared with patients
with low-risk (5.0% and 5.7%) and missing (3.5% and 3.2%) AMRs (P <.0001). Using
logistic regression, the 3-month AMR is more strongly associated with subsequent
ED visit or hospitalization than the 6-month AMR. CONCLUSIONS: AMR-based risk
assignment is relatively stable over time. Three-month AMR calculation periods
appear to provide the most accurate assessment of risk. Children with missing
AMRs likely have inactive asthma and are at the lowest risk for emergent asthma
visits.
PMID- 29939505
TI - Simply delivered meals: a tale of collaboration.
AB - Western medicine is undergoing a transition toward transparency of quality and
costs, and healthcare systems are striving to achieve the Triple Aim, a framework
for improving the patient experience of care, improving the health of
populations, and reducing the per capita cost of healthcare. Meanwhile, there is
growing recognition of the impact of social determinants of health and a new
federal requirement for nonprofit hospitals to implement prevention strategies. A
specialized meal delivery program called Simply Delivered for ME (SDM) was formed
in an effort to improve care and reduce 30-day hospital readmission rates.The
Maine Medical Center (MMC) partnered with the Southern Maine Agency on Aging to
offer SDM on a voluntary basis to high-risk Medicare patients already enrolled in
the Community-based Care Transition Program (CCTP) at MMC. We report the results
of the 2-year intervention in terms of 30-day hospital readmission rates and cost
measures (ie, return on investment and cost savings).Of the 622 MMC patients who
received SDM during the 24 months, the 30-day readmission rate was 10.3%
(compared with the 16.6% 30-day rate of hospital readmission at baseline [ie,
before the adoption of CCTP]) for all-cause readmissions. The cost savings for
reduced readmissions were $212,160. The return on investment was 387%, or a
benefit-cost ratio of $3.87 for every $1.00 spent on meals. Programs such as SDM
may reduce the rate of hospital readmission among high-risk older adults and,
thereby, yield lower healthcare costs.
PMID- 29939506
TI - Identifying children at risk of asthma exacerbations: beyond HEDIS.
AB - OBJECTIVES: Asthma is a costly and variable disease necessitating routine
population health monitoring. Insurance claims represent all paid pharmacy,
diagnostic, outpatient, inpatient, and emergency care; however, current claims
based identification tools may be overly specific. We sought to determine how
various definitions of asthma may improve detection of patients at risk of asthma
exacerbations. STUDY DESIGN: A statistical analysis of private insurance claims
for patients in a pediatric primary care network in Massachusetts. METHODS: We
performed a retrospective statistical analysis for patients aged 2 to 18 years
with 3 years of continuous enrollment. Multiple potential definitions were
constructed and tested on 2 years of data against their ability to identify
patients having an exacerbation in the third year. Definitions tested utilized
patterns of medication fills and visits billed with a diagnosis of asthma,
wheeze, or cough. We calculated the sensitivity and specificity of each
definition and constructed a receiver operating characteristic curve. RESULTS: In
a cohort of 28,363 patients, a definition identifying patients with 1 or more
clinician visits with a diagnosis of asthma or wheeze over 2 years was most
efficient in detecting patients with an exacerbation in the subsequent year
(sensitivity, 0.78; specificity, 0.84). When tested on the same cohort, the
Healthcare Effectiveness Data and Information Set (HEDIS) persistent asthma
criteria were less sensitive but more specific (sensitivity, 0.20; specificity,
0.99). CONCLUSIONS: Population health registries and quality measurement may
benefit from using a claims-based definition of pediatric patients at risk of
asthma exacerbations that is not as restrictive as the HEDIS persistent asthma
criteria.
PMID- 29939507
TI - Placement of selected new FDA-approved drugs in Medicare Part D formularies, 2009
2013.
AB - OBJECTIVES: To assess formulary decisions by Part D plans for selected newly
approved drugs. STUDY DESIGN: Retrospective cohort study. METHODS: Formulary
placement and restrictions were identified for 33 drugs in 8 therapeutic classes
(antihyperglycemics, anticoagulants, antiplatelets, disease-modifying agents for
multiple sclerosis [MS] and rheumatoid arthritis [RA], chronic obstructive
pulmonary disease [COPD] drugs, antiepileptics, and antipsychotics) in 863 Part D
plans with continuous CMS contracts between 2009 and 2013. Multivariable models
estimated the impact of drug characteristics and Part D plan characteristics on
probability of drug adoption and, for adopters, evaluated factors associated with
months to adoption and requirements for prior authorization (PA) or step therapy
(ST). RESULTS: First Part D formulary placements varied from 2 to 14 months post
FDA approval. On average, 56.7% of plans placed each drug within 6 months and
64.1% placed within 1 year of the National Drug Code assignment date. The most
rapid adoption was for antipsychotics and antiepileptics. The slowest was for
COPD drugs. More than 90% of disease-modifying agents for MS and RA were subject
to PA. ST was uncommon except for antihyperglycemic agents. In adjusted analyses,
enhanced benefit plans had a 4% higher probability of formulary placement (P
<.01), and each additional star in the CMS star rating system increased the
probability of adoption by 4% (P <.01). Overall, Medicare Advantage prescription
drug plans had higher placement rates due to greater reliance on enhanced plan
offerings and higher star ratings. CONCLUSIONS: We found significant
heterogeneity in formulary placement and restrictions for 33 new drugs in the
Part D marketplace between 2009 and 2013. Further research is necessary to
determine whether this pattern applies to other drug classes.
PMID- 29939508
TI - Cost sharing for antiepileptic drugs: medication utilization and health plan
costs.
AB - OBJECTIVES: To examine the association between health plan out-of-pocket (OOP)
costs for antiepileptic drugs and healthcare utilization (HCU) and overall plan
spending among US-based commercial health plan beneficiaries with epilepsy. STUDY
DESIGN: Retrospective cohort. METHODS: The Truven MarketScan Commercial Claims
database for January 1, 2009, to June 30, 2015, was used. Patients 65 years or
younger with epilepsy and at least 12 months of continuous enrollment before
index (date meeting first epilepsy diagnostic criteria) were included. Analyses
were adjusted for age group, gender, beneficiary relationship, insurance plan
type, and Charlson Comorbidity Index score. Primary outcomes included proportion
of days covered (PDC), HCU, and healthcare spending in 90-day postindex periods.
Associations between OOP costs and mean PDC, HCU, and plan healthcare spending
per 90-day period were estimated. RESULTS: Across 5159 plans, 187,241
beneficiaries met eligibility criteria; 54.3% were female, 41.7% were aged 45 to
65 years, and 62.4% were in preferred provider organization plans. Across
postindex 90-day periods, mean (SD) PDC, epilepsy-specific hospitalizations,
outpatient visits, and emergency department visits were 0.85 (0.26), 0.02 (0.13),
0.34 (0.47), and 0.05 (0.22), respectively. Median (interquartile range) spending
per 90-day period was $1488 ($459-$4705); median epilepsy-specific spending was
$139 ($18-$623). Multivariable linear regression without health plan fixed
effects revealed that higher OOP spending was associated with a decrease in PDC
(coefficient, -0.008; 95% CI, -0.009 to -0.006; P <.001) and an increase in
overall spending (218.6; 95% CI, 47.9-389.2; P = .012). Health plan fixed effects
model estimates were similar, except for epilepsy-specific spending, which was
significant (120.6; 95% CI, 29.2-211.9; P = .010). CONCLUSIONS: Increases in
beneficiaries' OOP costs led to higher overall spending and lower PDC.
PMID- 29939509
TI - Assessing markers from ambulatory laboratory tests for predicting high-risk
patients.
AB - OBJECTIVES: This exploratory study used outpatient laboratory test results from
electronic health records (EHRs) for patient risk assessment and evaluated
whether risk markers based on laboratory results improve the performance of
diagnosis- and pharmacy-based predictive models for healthcare outcomes. STUDY
DESIGN: Observational study of a patient cohort over 2 years. METHODS: We used
administrative claims and EHR data over a 2-year period for a population of
continuously insured patients in an integrated health system who had at least 1
ambulatory visit during the first year. We performed regression tree analyses to
develop risk markers from frequently ordered outpatient laboratory tests. We
added these risk markers to demographic and Charlson Comorbidity Index models and
3 models from the Johns Hopkins Adjusted Clinical Groups system to predict
individual cost, inpatient admission, and high-cost patients. We evaluated the
predictive and discriminatory performance of 5 lab-enhanced models. RESULTS: Our
study population included 120,844 patients. Adding laboratory markers to base
models improved R2 predictions of costs by 0.1% to 3.7%, identification of high
cost patients by 3.4% to 121%, and identification of patients with inpatient
admissions by 1.0% to 188% for the demographic model. The addition of laboratory
risk markers to comprehensive risk models, compared with simpler models, resulted
in smaller improvements in predictive power. CONCLUSIONS: The addition of
laboratory risk markers can significantly improve the identification of high-risk
patients using models that include age, gender, and a limited number of
morbidities; however, models that use comprehensive risk measures may be only
marginally improved.
PMID- 29939510
TI - Satisfaction with care after reducing opioids for chronic pain.
AB - OBJECTIVES: An epidemic of opioid overuse has resulted in nationwide efforts to
decrease prescribing, but there is concern that implementing these
recommendations will cause patients who are accustomed to opioids for chronic
pain to be dissatisfied with care. STUDY DESIGN: Retrospective cohort study of
satisfaction scores for patients prescribed opioids for noncancer chronic pain
for at least 6 consecutive months from 2009 to 2014. METHODS: We used mixed
effects regression to examine the association between opioid dose reduction and
the frequency of unfavorable patient satisfaction scores. Subgroup analysis
compared the effect of dose reduction on satisfaction scores for encounters
between patients and their assigned primary care provider (PCP) versus encounters
between patients and an unassigned provider. RESULTS: Included were 2492
encounters involving patients with high-dose chronic opioid use for noncancer
pain. A reduction in opioid prescribing occurred in 29% of encounters, and most
of these resulted in favorable satisfaction scores (86.4%). After adjustment, the
odds of an unfavorable score in the dose reduction group were just marginally
higher and not significant (odds ratio [OR], 1.31; 95% CI, 1.00-1.73). Stratified
by different encounter types, opioid dose reduction was not associated with
unfavorable scores for visits with an assigned PCP (OR, 1.16; 95% CI, 0.79-1.70),
but the odds of an unfavorable score were higher for encounters with an
unassigned provider (OR, 1.50; 95% CI, 1.01-2.23). CONCLUSIONS: Overall, reducing
opioid use for chronic pain is not associated with lower patient satisfaction
scores, but encounters with unassigned providers may be associated with slightly
lower satisfaction when opioids are reduced.
PMID- 29939511
TI - A c.3037G>A mutation in FBN1 gene causing Marfan syndrome with an atypically
severe phenotype.
AB - Marfan syndrome is a pleiotropic connective tissue disease inherited as
anautosomal dominant trait, mostly caused by mutations in the FBN1 gene, which is
located onchromosome 15q21.1 and encoding fibrillin 1. We report a case of Marfan
syndrome presentingwith severe ocular and systemic manifestations, such as
cardiac congenital anomalies.The patient underwent a multidisciplinary approach
and his clinical diagnosis was associatedwith a c.3037G>A mutation in the FBN1
gene. Identification of this genetic alteration shouldinstigate a prompt
multidisciplinary assessment and monitoring, in order to prevent
devastatingconsequences such as cardiac and ocular phenotype. Molecular modeling
of the mutationhighlighted the importance of the preservation of the calcium
dependent structure of an epidermal-growth-factor-like domain of fibrillin-1 and
consequently the microfibrillar formationprocess. This report aims to highlight
the importance of an early clinical and molecular diagnosisand once more, the
importance of the multidisciplinary approach of this genetic entity.
PMID- 29939512
TI - Evidences about combination use of acetylsalicylic acid (aspirin) and clopidogrel
in acute coronary syndrome.
AB - Thromboembolic diseases remain one of the most important causes of morbidity and
mortality worldwide. The pathophysiologic mechanism underlying the acute coronary
syndromes is coronary thrombosis. That is why the basis of its treatment has
focused on antiplatelet, fibrinolytic and anticoagulant drugs. In a significant
number of individuals, additional measures must be used, such as, for example,
the coronary percutaneous intervention (angioplasty and placement of the so
called intracoronary stents). Aspirin has been regarded as the drug of first
choice in the prevention of thromboembolic diseases. The combination aspirin
clopidogrel has represented a highly efficient therapeutic measure for
thromboembolic events. The introduction of fixed combination tablets represents a
step forward in order to facilitate therapeutic compliance.
PMID- 29939513
TI - The Experience of Plague in East Kent, 1636-38.
AB - On 2 July 1637 43-year-old Elizabeth Burgess, from Canterbury, was buried at
Birchington, Kent, having died of the plague in the hamlet of Wood in that
parish. She was the first victim of an outbreak of plague in 1637. This article
firstly examines that outbreak in Birchington in detail; then it considers how
far the parish's experience matched that in nearby Faversham and Sandwich. It
finally discusses the extent to which the infection spread to the surrounding
area.
PMID- 29939514
TI - Urban Family Reconstitution-A Worked Example.
AB - Family reconstitutions have been undertaken only rarely in urban settings due to
the high mobility of historical urban populations, in both life and death.
Recently Gill Newton has outlined a methodology for the reconstitution of urban
populations and we applied a modified version of this method to the large
Westminster parish of St. Martin in the Fields between 1752 and 1812, a period
that posed particular difficulties for family reconstitution because of the rapid
lengthening of the interval between birth and baptism. The extraordinary richness
of the records for St. Martin in the Fields made it possible to investigate
burial and baptismal practices in great detail, and the extent and impact of
residential mobility. We found that short-range, inter-parochial movement was so
frequent that it was necessary to confine the reconstitution sample to windows in
which families registered events at a single street address. Using birth interval
analysis and the frequencies of twin births it was possible to demonstrate that
the registration of birth events was fairly complete, but that many infant and
child burials were missed. These missing burials probably resulted from the
unreported export of corpses for burial in other parishes, a phenomenon for which
we had considerable evidence. The limitations of family reconstitution in this
highly mobile and heterogeneous urban population is discussed and we demonstrate
some checks and corrections that can be used to improve the quality of such
reconstitutions.
PMID- 29939515
TI - A Study of Bigamists in Pre-Victorian London.
AB - This article explores the potential reasons for and extent of bigamy in London in
the early nineteenth century. The nature of the criminal offence is considered,
examining the evidence required to secure a conviction, and the penalties
imposed. Based largely on records of Old Bailey convictions, together with
associated newspaper reports, the varied personal circumstances of those involved
are noted. Some were victims of the system; others were exploited targets of
their callous partner. Gender distinctions are considered and the sentences
imposed analysed to ascertain how they reflected society's view of the particular
misconduct.
PMID- 29939695
TI - Perimortem Cesarean Section.
PMID- 29939696
TI - The NuMask(r) is as Effective as the Face Mask in Achieving Maximal
Preoxygentation.
AB - Background: Preoxygenation before anesthetic induction is a widely accepted
maneuver toincrease oxygen reserves and delay desaturation during apnea. There is
limited data regarding theuse of the NuMask(r) in the perioperative setting, and
no data as to its efficacy in achieving maximalpreoxygenation. We hypothesize
that the NuMask(r) may be a useful alternative to the face mask inachieving
maximal preoxygenation.Methods: After IRB approval, the NuMask(r) was compared
with the classic face maskwith respect to achieving maximal pre-oxygenation in 30
healthy volunteers using tidal volumebreathing. All volunteers were tested for
three periods of 5 minutes intervals and the followingparameters were recorded
every 30 seconds: inspired, and end-tidal oxygen concentration and endtidalcarbon
dioxide concentration.Results: The mean ETO2 of >=90% was achieved with both
masks at 3.5 minutes (SD =1.62 and 1.98 for facemask and NuMask(r) respectively)
and thereafter the ETO2 remained above90%. There were no statistical differences
noted in FiO2 and ETO2 between the face mask and theNuMask(r) in the same time
periods. ETCO2 values were also not statistically different between thetwo
masks.Conclusions: The study showed that the NuMask(r) is as effective as the
classic face mask inachieving maximal pre-oxygenation during tidal volume
breathing.Introduction
PMID- 29939697
TI - Effect of induced acute mild arterial hypertension on postoperative analgesic
requirements after laparoscopic ovarian cystectomy: a randomized double blinded
study.
AB - Objective: To evaluate the effectiveness of inducing acute hypertension during
laparoscopicovarian cystectomy on postoperative nalbuphine analgesic
requirements. Methods: The total dose of nalbuphine used in the hypertension
group was significantly lowerthan that in the control group (p <0.001). The VAS
score was significantly lower in the hypertensiongroup on arrival to PACU and
during the period between 1 and 6 hours postoperatively. Results: The total dose
of nalbuphine used in the hypertension group was significantly lowerthan that in
the control group (p <0.001). The VAS score was significantly lower in the
hypertensiongroup on arrival to PACU and during the period between 1 and 6 hours
postoperatively. Conclusion: This study demonstrates that pharmacologically
induced mild acuteintraoperative hypertension significantly reduces postoperative
nalbuphine consumption and painscores following laparoscopic ovarian cystectomy.
Trial registration in Pan African Clinical TrialRegistry: identification number
for the registry is PACTR201508001247179.
PMID- 29939698
TI - Analgetic Efficacy of Flurbiprofen Axcetil in Rigid Cystoscopy for Men: a
Prospective Study.
AB - Objective: To evaluate the analgesic effect of preprocedural flurbiprofen axetil
on rigidcystoscopy-associated pain for men. Methods: Fifty-two men scheduled for
cystoscopy were recruited in this study. The effectsof oxybuprocaine jelly alone
or in combination with preprocedural flurbiprofen axetil, werecompared. The pain
intensity was assessed using visual analogue scale (VAS) scores duringinjecting
oxybuprocaine jelly into the urethra, during inserting rigid cystoscope into the
urethra,during viewing inside the urinary bladder, at the first urination after
cystoscopy and at the firsturination on the following morning at home. Results:
VAS scores with preprocedural flurbiprofen axetil were significantly lower
ascompared with the control group at the time periods of inserting rigid
cystoscope into the urethra,viewing inside the urinary bladder, the first
urination after cystoscopy and at the first urination onthe following morning at
home. No side effects associated with flurbiprofen axetil were observed.
Conclusion: Preprocedural flurbiprofen axetil can decrease cystoscopy-associated
pain.
PMID- 29939700
TI - Nasotracheal Intubation with Parker Flex-Tip Versus Preformed Nasal Endotracheal
Tubes for Children Undergoing Adenotonsillectomy.
AB - Abstract: The design of the endotracheal tube might be an important factor in the
incidence of injurious complications during nasotracheal intubation. Aim of the
work: Primary aim: to compare the parker flex tip (PFT) and the preformed
nasal(PNT) tubes regarding the ease of insertion during nasotracheal intubation
in children undergoingadenotonsillectomy. Secondary aim: to verify the incidence
of traumatic complications of bothtypes of tubes during nasotracheal intubation
in children undergoing adenotonsillectomy. Patients and methods: 100 patients
aged between 4 and 10 years ASA physical status I-IIscheduled for
adenotonsillectomy were divided into two groups; Group PFT: Patients were
nasallyintubated using the parker flex-tip endotracheal tube, Group PNT: Patients
were nasally intubatedusing the preformed nasal tube. Ease of insertion of the
ETT, degree of trauma and the time ofintubation was measured. Results: ETT was
easily inserted without any resistance in 24% of patients of the PFT groupversus
12% of patients in the PNT group. ETT could not be passed through the right or
left nostrilsin 20% of patients of the PNT group relative to only 4% of patients
of the PFT group. Incidence oftrauma to the nasal mucosa was significantly higher
in patients of the PNT group than patients ofthe PFT group. Duration of
intubation was statistically significantly longer among patients of thePNT group
than patients of the PFT group. Conclusions: It seems that the flexible tapered
tip of the PFT tube has led to easierinsertion through the nasal passages as well
as less trauma to the nasal mucosa in children havingnasopharyngeal pathology in
the form of adenoids. At the same time, the duration of intubation wasless in the
PFT group relative to the control group in spite of the more familiarity of the
investigatorwith the standard portex tube.
PMID- 29939701
TI - Effects of Circuit Leak Development Over Time and Response During Low-Flow Volume
and Pressure-Controlled Ventilation.
AB - Study Objective: To study the effects of circuit leak development over time and
response during volume and pressure controlled ventilation using low flow in
human patient simulator and to examine the minimum fresh gas flow needed to
compensate for such a leak.Design/Setting: Prospective study using a patient
Simulation Lab at Wayne State University.Measurements: A human patient simulator
was endotracheally intubated. The endotrachealtube (ETT) was connected to the
Datex-Ohmeda AS/3 Anesthesia machine. The tidal volume wasset to 500ml in the
volume controlled trial and the pressure to 6cm H2O in the pressure
controlledtrial. A hole was created in each experiment placed 10 cm after the
inspiratory valve. Leaks weresimulated from holes using 4 different needle
diameters: 25, 21, 18 and 16G. A series of data werecollected using fresh gas
flow at 4 different flow rates (0.5, 1, 1.5 and 2 liters.min-1). Data wasmeasured
at different time points (baseline, 1, 3 and 5 minutes) in the series of
simulated leakingbreathing circuits.Results: Leak alarms were only detected with
16G hole at 5 minutes in the volume controlmode versus leaks at 3 minutes with
16G hole and at 5 minutes with 18G hole in the pressurecontrol mode.Conclusion:
When a very low flow of 0.5 L/min is used, volume control is safer than pressure
control modes.
PMID- 29939702
TI - Clinical exposure and organization of the Critical Care rotation during the Hajj
periods in 1434-1435; perspectives of Arabian Saudi AnesthesiologyProgram
Residents.
AB - Background: Background: The nature of massive mass gathering during Hajj was
expected to provide achallenging and stimulating working experience for
anesthesiology training program residents. Annew rotation arrangement was reached
between the Ministry of Health and the Saudi Commissionof Health Specialties to
recruit anesthesia resident to provide critical care services during the
Hajjseasons in 1434 and 1435. Objectives: This study aimed to explore the
perspectives of anesthesia residents on theirexperience working among critical
care teams during Hajj seasons in 1434H and 1435H at variouslocations of Makkah
city and Al-Mashaer. Subjects and methods: This cross-sectional study was
conducted using a self-administeredquestionnaire distributed to all residents (n
= 35) enrolled in anesthesia residency training programof the SCFHS and
participated in critical care areas as locum during the Hajj seasons of 1434H
and1435H. Data was analyzed by using the statistical package of social science.
Results: The mean score of residents agreement on being treated with respect from
bothnurses and administration was the highest among the surveyed item (6.13 and
6.22 respectively). Itwas observed that, satisfaction of the residents with the
direct observations and feedback providedto them (p = 0.01), the adequacy of the
services components (p = 0.01) being treated with respectby the senior doctors
and nurses (p = 0.03, p = 0.002) was significantly increased in the year
1435compared to that of the year 1434. The satisfaction was generally higher in
Makkah hospitals whencompared to that of Al-Mashaer (Arafat and Menna) hospitals
although this difference was of no statistical significance. Conclusion: Hajj
critical care rotations in 1434 and 1435 were well perceived by
anesthesiaresidents. They found them useful as they give them the chance to gain
self-confidence andexperience the provision of healthcare services for mass
gathering sessions.
PMID- 29939703
TI - Ultrasound Guided In-Plane Penile Nerve Block for Circumcision: A New, Modified
Technique Suggests Lower Anesthetic Volume and Narcotic Use.
AB - Context: Circumcision is one of the most common surgical procedures in pediatric
males.Anesthesia is often the classic dorsal penile nerve block (DPNB), which is
based on landmarkidentification and tactile feel of tissue resistance during
needle advancement. However, thistechnique is associated with technical failures
and vascular complications. Objective: We used an ultrasound-guided in-plane
technique to avoid injury of penilevascular and neural tissues during DPNB. The
aims of this retrospective study were to compare thesuccess rate and efficacy of
these two penile block techniques. Methods: Male pediatric patients undergoing
circumcision received general anesthesiabefore the penis and surrounding area
were prepared with 0.5% chlorhexidine in 70% alcohol.Sixteen patients underwent
classic DPNB, and 16 underwent the modified ultrasound-guided inplanetechnique.
The ultrasound machine was adjusted to the musculoskeletal setting, and a
linearultrasound probe with a frequency range of 5 to 10 MHz was placed
transversely along the base of the penis, which received gentle traction.
Results: Though not statistically significant, patients who underwent the classic
DPNB wereapproximately 1.8 times more likely to require rescue analgesia and
approximately 2 times morelikely to have a complication than those in the
ultrasound-guided group. Results also showed lowervolume requirements for local
anesthetic and intraoperative narcotics, longer time until rescueanalgesic, and
lower incidence of vomiting in the ultrasound-guided group than in the landmark
guided group. Conclusions: The ultrasound-guided DPNB technique appears to offer
advantages overclassic DPNB and warrants a prospective controlled trial to
confirm these findings.
PMID- 29939704
TI - Dose-Dependent Anti-Inflammatory Effect of Ketamine in Liver Ischemia-Reperfusion
Injury.
AB - Introduction: Hepatic ischemia-reperfusion (I/R) injury is commonly observed in
severesepsis, hemorrhagic shock, liver transplantation, hepatic resection, and
major trauma. Ketaminesuppresses the production of cytokines, such as IL-6 and
TNF-alpha, via NF-kappaB inhibition. Weinvestigated the anti-inflammatory effects
of ketamine in liver I/R injury. Materials and Methods: Female Wistar-Albino rats
(n = 18), weighing 150-200g, weredivided into three groups (n = 6 each). Group I
underwent reperfusion for 4h following 30 minof ischemia. Group II received 2.5
mg/kg ketamine IM following 30 min of ischemia and 4h ofreperfusion and Group III
received 10 mg/kg ketamine IM following 30 min of ischemia and 4h ofreperfusion.
Blood samples were obtained before and after ischemia and reperfusion. MDA,
AST,ALT, TNF-alpha, IL-1beta, IL-6, and NO levels were determined. Liver tissue
samples were evaluatedhistologically. Results: Increased TNF-alpha, IL-1beta, and
IL-6 levels were observed in all groups post-ischemiaversus pre-ischemia (p
<0.05). The TNF-alpha, IL-1beta, and IL-6 levels in Group III increased less
thanthey did in Groups I and II (p <0.05). Higher MDA, NO, AST, and ALT levels
were found duringthe ischemia and reperfusion periods compared with during the
pre-ischemia period in all groups (p<0.05). The MDA, NO, AST, and ALT levels of
rats that received ketamine increased less than didthose of Group I (p <0.05).
Significantly less injury was observed in the histopathological analysisof livers
of rats administered ketamine (p <0.05). Conclusions: Ketamine showed a dose
dependent anti-inflammatory effect in I/R injury inthe liver when administered
after ischemia.
PMID- 29939705
TI - Anesthetic Management of Advanced Stage Ludwig's Angina: A Case Report and Review
With Emphasis on Compromised Airway Management.
AB - Ludwig's angina, although uncommon, remains a potentially life-threatening
condition because of the risk of impending airway obstruction. Effective
treatment is based on early recognition of the clinical process, with the
appropriate use of parenteral antibiotics, securing the airway, and formal
surgical drainage of the infection. Awake fiberoptic intubation under topical
anesthesia may be the preferred method to secure the airway. Flexible
nasotracheal intubation requires skill and experience. When fiberoptic
bronchoscopy is not feasible, not available, or has failed, an elective awake
cricothyrotomy and tracheostomy are the options. Furthermore, the introduction of
newer advanced airway techniques, such as video-assissted laryngoscopy, may allow
the clinician additional flexibility in nonsurgical airway management. We present
a recent case of a patient with Ludwig's angina, successfully managed at our
hospital, with a brief review of airway management options.
PMID- 29939706
TI - Post-Partum Malignant Hypertension in a Patient with Preeclampsia and Abruptio
Placenta.
PMID- 29939707
TI - The Use of Flexible Fiberoptic Cystoscope for Difficult Endotracheal Intubation
in TMJ Ankylosis Patients: A Case Series.
AB - Background: Fiberoptic bronchoscopes might be vital for the safe performance of
difficultendotracheal intubations. However, many hospitals in low or middle
income countries are unableto afford the equipment. We describe the use of a
flexible fiberoptic cystoscope, as an alternativeto a bronchoscope, for difficult
nasoendotracheal intubation in patients with temporomandibular joint ankyloses.
Methods: Eight Jordanian patients (five females and three males) with severe
restriction ofmouth opening, due to ankylosis of the temporomandibular joint,
underwent awake nasoendotrachealintubation using a flexible fiberoptic cystoscope
under local anesthesia. Results: The procedure was successful and well tolerated
in all eight patients. Conclusion: A flexible cystoscope can be a successful
alternative to a flexible bronchoscope,for difficult nasoendotracheal intubation
in hospitals at rural areas in low-or middle-income countries with limited
financial resources.
PMID- 29939708
TI - Biological Self-Assembly and Recognition Used to Synthesize and Surface Guide
Next Generation of Hybrid Materials.
AB - Free-standing, high aspect ratio sulfur-doped carbon nanodot-based hybrid
nanowires with a microtubular aspect were synthesized using self-recognition and
self-assembly processes of tubulin, a biological molecule precursor of the
cytoskeletal microtubule. Physicochemical characterizations (e.g., morphology,
diameter, spectral characteristics, etc.) of such user-synthesized hybrid
bionanowires were performed using classical atomic and spectroscopic techniques,
whereas bioactivity and functionality testing was demonstrated by mimicking
cellular transport based on kinesin, a motor protein capable to recognize, and
move on the microtubules. Our results indicate that user-synthesized hybrid
nanowires could be manipulated in vitro under constant chemical energy of
adenosine triphosphate and have the potential to be implemented in the next
generation of synthetic applications from drug delivery to diagnosis systems, and
photocatalytic to optical devices.
PMID- 29939709
TI - Development of a High-Throughput, In Vivo Selection Platform for NADPH-Dependent
Reactions Based on Redox Balance Principles.
AB - Bacteria undergoing anaerobic fermentation must maintain redox balance. In vivo
metabolic evolution schemes based on this principle have been limited to
targeting NADH-dependent reactions. Here, we developed a facile, specific, and
high-throughput growth-based selection platform for NADPH-consuming reactions in
vivo, based on an engineered NADPH-producing glycolytic pathway in Escherichia
coli. We used the selection system in the directed evolution of a NADH-dependent
d-lactate dehydrogenase from Lactobacillus delbrueckii toward utilization of
NADPH. Through one round of selection, we obtained multiple enzyme variants with
superior NADPH-dependent activities and protein expression levels; these mutants
may serve as important tools in biomanufacturing d-lactate as a renewable polymer
building block. Importantly, sequence analysis and computational protein modeling
revealed that diverging evolutionary paths during the selection resulted in two
distinct cofactor binding modes, which suggests that the high throughput of our
selection system allowed deep searching of protein sequence space to discover
diverse candidates en masse.
PMID- 29939710
TI - Redox Engineering of Cytochrome c using DNA Nanostructure-Based Charged
Encapsulation and Spatial Control.
AB - Three-dimensional (3D) DNA nanostructures facilitate the directed self-assembly
of various objects with designed patterns with nanometer scale addressability.
Here, we report the enhancement of cytochrome c (cyt c) redox activity by using a
designed 3D DNA nanostructure attached to a gold electrode to spatially control
the position of cyt c within the tetrahedral framework. Charged encapsulation and
spatial control result in the significantly increased redox potential and
enhanced electron transfer of this redox protein when compared to cyt c directly
adsorbed on the gold surface. Two different protein attachment sites on one
double stranded edge of a DNA tetrahedron were used to position cyt c inside and
outside of the cage. Cyt c at both binding sites show similar redox potential
shift and only slight difference in the electron transfer rate, both orders of
magnitude faster than the cases when the protein was directly deposited on the
gold electrode, likely due to an effective electron transfer pathway provided by
the stabilization effect of the protein created by the DNA framework. This study
shows great potential of using structural DNA nanotechnology for spatial control
of protein positioning on electrode, which opens new routes to engineer redox
proteins and interface microelectronic devices with biological function.
PMID- 29939711
TI - Bone Targeted Delivery of SDF-1 via Alendronate Functionalized Nanoparticles in
Guiding Stem Cell Migration.
AB - Stem cells are well-known for their great capacity for tissue regeneration. This
provides a promising source for cell-based therapies in treating various bone
degenerative disorders. However, the major hurdles for their application in
transplantation are the poor bone marrow homing and engraftment efficiencies.
Stromal cell-derived factor 1 (SDF-1) has been identified as a major stem cell
homing factor. With the aims of bone targeted SDF-1 delivery and regulating MSCs
migration, alendronate modified liposomal nanoparticles (Aln-Lipo) carrying SDF-1
gene were developed in this study. Alendronate modification significantly
increased the mineral binding affinity of liposomes, and facilitated the gene
delivery to osteoblastic cells. Up-regulated SDF-1 expression in osteoblasts
triggered MSCs migration. Systemic infusion of Aln-Lipo-SDF-1 with fluorescence
labeling in mice showed the accumulation in osseous tissue by biophotonic
imaging. Corresponding to the delivered SDF-1, the transplanted GFP+ MSCs were
attracted to bone marrow and contributed to bone regeneration. This study may
provide a useful technique in regulating stem cell migration.
PMID- 29939712
TI - Melanin Nanoparticle-Incorporated Silk Fibroin Hydrogels for the Enhancement of
Printing Resolution in 3D-Projection Stereolithography of Poly(ethylene glycol)
Tetraacrylate Bio-ink.
AB - It is not easy to design structures with transparent solutions, especially in
light projection three-dimensional (3D) printing, since the penetration of light
in solution is limitless. Here, silk fibroin incorporated with melanin
nanoparticles (SFM) is used as a transparency modifier of poly(ethylene glycol)
tetraacrylate (PEG4A) solution. The incorporation of melanin into the SF hydrogel
is performed in the range of 0.05-0.2% (w/v), and the SFM was added to the PEG4A
precursor solution at 0.25-1.0% (w/v). The printing accuracy was examined by
comparing the printed and designed feature sizes. The addition of 1.0% (w/v) SFM
to a 4% (w/v) PEG4A (PEG4A/SFM) precursor solution effectively reduces the
transparency of the solution and improves the printing resolution by confining
the light beam to a designed region. This enables the fabrication of hard-to
express features such as hollow blood vessels or vacant tubes. Furthermore, the
elastic modulus of the printed PEG4A/SFM composite hydrogel increases 2.5-fold
higher than the PEG4A hydrogel without SFM. For the bio-ink, PEG4A/SFM-containing
cells show non-cytotoxicity and improve the proliferation rate of embedded cells,
confirming the high biocompatibility of PEG4A/SFM hydrogels.
PMID- 29939713
TI - Hybrid Polymer/Metal-Organic Framework Films for Colorimetric Water Sensing over
a Wide Concentration Range.
AB - Because of their extraordinary surface areas and tailorable porosity, metal
organic frameworks (MOFs) have the potential to be excellent sensors of gas-phase
analytes. MOFs with open metal sites are particularly attractive for detecting
Lewis basic atmospheric analytes, such as water. Here, we demonstrate that thin
films of the MOF HKUST-1 can be used to quantitatively determine the relative
humidity (RH) of air using a colorimetric approach. HKUST-1 thin films are spin
coated onto rigid or flexible substrates and are shown to quantitatively
determine the RH within the range of 0.1-5% RH by either visual observation or a
straightforward optical reflectivity measurement. At high humidity (>10% RH), a
polymer/MOF bilayer is used to slow the transport of H2O to the MOF film,
enabling quantitative determination of RH using time as the distinguishing
metric. Finally, the sensor is combined with an inexpensive light-emitting diode
light source and Si photodiode detector to demonstrate a quantitative humidity
detector for low humidity environments.
PMID- 29939714
TI - Fine Tuning of Emission Behavior, Self-Assembly, Anion Sensing, and Mitochondria
Targeting of Pyridinium-Functionalized Tetraphenylethene by Alkyl Chain
Engineering.
AB - Compared to the many studies that focus on the development of novel molecular
frameworks pertaining to functionalized fluorescent materials, there is lesser
emphasis on side chains even though they have a significant impact on the
properties and applications of fluorescent materials. In this study, a series of
pyridinium-functionalized tetraphenylethene salts (TPEPy-1 to TPEPy-4) possessing
different alkyl chains are synthesized, and the influence of chain length on
their optical performance and applications is thoroughly investigated. By
changing the alkyl chain, the fluorogens exhibit opposite emission behavior in
aqueous media because of their distinct hydrophobic nature, and their solid-state
emission can be fine-tuned from green to red owing to their distinct molecular
configuration. In addition, by increasing the chain length, the microstructure of
the self-assembled fluorogens converts from microplates to microrods with various
emission colors. Moreover, TPEPy-1 exhibits dual-mode fluorescence "turn-on"
response toward NO3- and ClO4- in aqueous media because the anions induce the
self-assembly of fluorogens. Furthermore, the fluorogens display cellular uptake
selectivity while the proper alkyl chain impels the fluorogens to penetrate the
cell membrane and accumulate in the mitochondria with high specificity.
PMID- 29939715
TI - Super Antiwetting Surfaces for Mitigating Drag-Out of Deep Eutectic Solvents.
AB - Deep eutectic solvents (DESs) are, at room temperature, about dozens to hundreds
of times more viscous than water, which brings pretty thick residues on solid
surfaces, for example, causing drag-out and weight loss in the transfer process.
Unfortunately, until now little work had been done for solving this knotty
problem. In this study, the super antiwetting surface, i.e., super-DES-phobic
surface (defined as DES contact angle > 150 degrees ) is proposed and fabricated
successfully by a facile coating technique. Hierarchical silver dendrites on
copper foam substrate provide effective dual-roughness surfaces showing stable
superDESphobicity. The superDESphobic surface can repel the DESs and their
derived solutions even under elevated temperature of about 120 degrees C and the
impact attack of drops. It is also found that the superDESphobic surface can
significantly delay the DESs freezing and reduce the adhesion strength of the
frozen DESs. Interestingly, the superDESphobic surface can be applied as an
effective tool for gauging the density of DES using an ~2 MUL droplet in virtue
of its super antiwetting property. The super antiwetting surfaces show promise
for potential applications in DES self-cleaning and antifreezing.
PMID- 29939716
TI - Utilizing a Mini-Humidifier To Deposit Matrix for MALDI Imaging.
AB - MALDI mass spectrometry imaging (MALDI-MSI) is a powerful tool to study
endogenous metabolites. The process of matrix deposition is crucial for a high
quality imaging result. Commercial instruments for matrix deposition are
expensive. Low-cost methods like airbrushing will generate matrix crystals that
are too large for high-spatial-resolution imaging. Sublimation may cause some
compounds to go undetected because of the lack of solvent. Herein, we utilized a
mini-humidifier, costing less than 5 dollars, to deposit matrix for MALDI-MSI.
Compared with Imageprep, a commercialized instrument, our device based on the
humidifier provided higher sensitivity and much smaller matrix crystals with
diameters of less than 10 MUm. High-quality ion images with 10 MUm spatial
resolution were obtained using our method. The enhancement of sensitivity by the
humidifier could provide a sufficient amount of ions to perform tandem mass
imaging. We also performed MALDI-MS/MS imaging to separate two lipids in mouse
brain.
PMID- 29939717
TI - Low Thermal Boundary Resistance Interfaces for GaN-on-Diamond Devices.
AB - The development of GaN-on-diamond devices holds much promise for the creation of
high-power density electronics. Inherent to the growth of these devices, a
dielectric layer is placed between the GaN and diamond, which can contribute
significantly to the overall thermal resistance of the structure. In this work,
we explore the role of different interfaces in contributing to the thermal
resistance of the interface of GaN/diamond layers, specifically using 5 nm layers
of AlN, SiN, or no interlayer at all. Using time-domain thermoreflectance along
with electron energy loss spectroscopy, we were able to determine that a SiN
interfacial layer provided the lowest thermal boundary resistance (<10 m2K/GW)
because of the formation of an Si-C-N layer at the interface. The AlN and no
interlayer samples were observed to have TBRs greater than 20 m2K/GW as a result
of a harsh growth environment that roughened the interface (enhancing phonon
scattering) when the GaN was not properly protected.
PMID- 29939718
TI - Atomic Scale Photodetection Enabled by a Memristive Junction.
AB - The optical control of atomic relocations in a metallic quantum point contact is
of great interest because it addresses the fundamental limit of "CMOS scaling".
Here, by developing a platform for combined electronics and photonics on the
atomic scale, we demonstrate an optically controlled electronic switch based on
the relocation of atoms. It is shown through experiments and simulations how the
interplay between electrical, optical, and light-induced thermal forces can
reversibly relocate a few atoms and enable atomic photodetection with a digital
electronic response, a high resistance extinction ratio (70 dB), and a low OFF
state current (10 pA) at room temperature. Additionally, the device introduced
here displays an optically induced pinched hysteretic current (optical
memristor). The photodetector has been tested in an experiment with real optical
data at 0.5 Gbit/s, from which an eye diagram visualizing millions of detection
cycles could be produced. This demonstrates the durability of the realized atomic
scale devices and establishes them as alternatives to traditional photodetectors.
PMID- 29939719
TI - Mapping the Conductance of Electronically Decoupled Graphene Nanoribbons.
AB - With the advent of atomically precise synthesis and consequent precise tailoring
of their electronic properties, graphene nanoribbons (GNRs) have emerged as
promising building blocks for nanoelectronics. Before being applied as such, it
is imperative that their charge transport properties are investigated. Recently,
formation of a molecular junction through the controlled attachment of
nanoribbons to the probe of a scanning tunneling microscope (STM) and subsequent
lifting allowed for the first conductance measurements. Drawbacks are the
perturbation of the intrinsic electronic properties through interaction with the
metal surface, as well as the risk of current-induced defect formation which
largely restricts the measurements to low bias voltages. Here, we show that
resonant transport-essential for device applications-can be measured by lifting
electronically decoupled GNRs from an ultrathin layer of NaCl. By varying the
applied voltage and tip-sample distance, we can probe resonant transport through
frontier orbitals and its dependence on junction length. This technique is used
for two distinct types of GNRs: the 7 atom wide armchair GNR and the 3,1-chiral
GNR. The features in the conductance maps can be understood and modeled in terms
of the intrinsic electronic properties of the ribbons as well as capacitive
coupling to tip and substrate. We demonstrate that we can simultaneously measure
the current decay with increasing junction length and bias voltage by using a
double modulation spectroscopy technique. The strategy described in this work is
widely applicable and will lead to a better understanding of electronic transport
through molecular junctions in general.
PMID- 29939720
TI - Exploring the Nonconserved Sequence Space of Synthetic Expression Modules in
Bacillus subtilis.
AB - Increasing protein expression levels is a key step in the commercial production
of enzymes. Predicting promoter activity and translation initiation efficiency
based solely on consensus sequences have so far met with mixed results. Here, we
addressed this challenge using a "brute-force" approach by designing and
synthesizing a large combinatorial library comprising ~12 000 unique synthetic
expression modules (SEMs) for Bacillus subtilis. Using GFP fluorescence as a
reporter of gene expression, we obtained a dynamic expression range that spanned
5 orders of magnitude, as well as a maximal 13-fold increase in expression
compared with that of the already strong veg expression module. Analyses of the
synthetic modules indicated that sequences at the 5'-end of the mRNA were the
most important contributing factor to the differences in expression levels,
presumably by preventing formation of strong secondary mRNA structures that
affect translation initiation. When the gfp coding region was replaced by the
coding region of the xynA gene, encoding the industrially relevant B. subtilis
xylanase enzyme, only a 3-fold improvement in xylanase production was observed.
Moreover, the correlation between GFP and xylanase expression levels was weak.
This suggests that the differences in expression levels between the gfp and xynA
constructs were due to differences in 5'-end mRNA folding and consequential
differences in the rates of translation initiation. Our data show that the use of
large libraries of SEMs, in combination with high-throughput technologies, is a
powerful approach to improve the production of a specific protein, but that the
outcome cannot necessarily be extrapolated to other proteins.
PMID- 29939721
TI - Metals in the European Marine Strategies Legislation: A Challenge for the
Managers and Decision-Makers.
PMID- 29939722
TI - Air-Seawater Gas Exchange and Dry Deposition of Chlorinated Paraffins in a
Typical Inner Sea (Liaodong Bay), North China.
AB - As a group of new persistent organic pollutants, short-chain chlorinated
paraffins (SCCPs) and medium-chain CP (MCCPs) have attracted extensive worldwide
interest in recent years. However, the data regarding to the environmental
behavior, especially in atmospheric transfer and air-seawater exchange, are still
sparse. In this study, seasonal marine boundary layer air and seawater samples
were collected from Chinese Bohai sea and a fugacity model was built to evaluate
the air-seawater diffusion and deposition flux of CPs. Generally, the total CP
levels in atmosphere and seawater samples in summer were higher than those in
spring, and CPs existed mostly in the gaseous phase in air and the dissolved
phase in seawater. For SCCPs, C10 and C11 components were the most abundant
homologue groups. For MCCPs, the C14 homologue dominated in the particle phase of
atmosphere and particulate phase of seawater. The logarithmic fugacity ratios
(log fa/ fw) of higher chlorinated congeners (Cl8 to Cl10: 0.71 to 1.32 in May
and 1.38 to 2.29 in August) indicated that net deposition was the predominant
process, whereas lower chlorinated congeners, especially Cl5 homologue groups in
August, showed a trend of net volitization (log fa/ fw < -0.5). The results of
diffusion and dry deposition fluxes indicated that air-seawater gas exchange of
CPs was significantly higher than dry deposition in the sampling areas.
PMID- 29939723
TI - Strategy to Enhance the Luminescence of Lanthanide Ions Doped MgWO4 Nanosheets
through Incorporation of Carbon Dots.
AB - Highly fluorescent nanomaterials have shown great potential application in optics
area. However, further improving their fluorescence properties especially for
nanomaterials still remains a challenge. Specifically, luminescence of lanthanide
(Ln) ions doped two-dimensional (2D) nanosheets is seldom studied. Herein,
MgWO4:Ln3+ (Ln = Eu, Tb) nanosheets were successfully synthesized via a simple
hydrothermal method, and the luminescence properties of these nanosheets are
obviously improved through incorporation of fluorescent carbon dots (CDs) onto
the surface of MgWO4:Ln3+ (CDs@MgWO4:Ln3+) nanosheets. The obtained MgWO4:Ln3+
samples have a 2D nanosheet morphology with triclinic phase, and the morphology
and phase structure can be maintained after incorporating CDs onto the
nanosheets' surface. Under the excitation of UV light, the obtained MgWO4:Ln3+
nanosheets exhibit the characteristic emission of the doping ions, and the
emission intensity of CDs@MgWO4:Eu3+ and CDs@MgWO4:Tb3+ nanosheets increases 2-
and 7-fold compared to the corresponding samples without incorporation of CDs,
respectively. This luminescent enhancement mechanism might be due to the
capturing electrons by CDs and energy transfer from CDs to luminescent Ln3+. The
fluorescence enhancement through incorporation of CDs provides a simple and
environment-friendly strategy for further improving luminescence property of
other lanthanide ions doped nanomaterials.
PMID- 29939724
TI - Key Residues Affecting Transglycosylation Activity in Family 18 Chitinases:
Insights into Donor and Acceptor Subsites.
AB - Understanding features that determine transglycosylation (TG) activity in
glycoside hydrolases is important because it would allow the construction of
enzymes that can catalyze controlled synthesis of oligosaccharides. To increase
TG activity in two family 18 chitinases, chitinase D from Serratia proteamaculans
( SpChiD) and chitinase A from Serratia marcescens ( SmChiA), we have mutated
residues important for stabilizing the reaction intermediate and substrate
binding in both donor and acceptor sites. To help mutant design, the crystal
structure of the inactive SpChiD-E153Q mutant in complex with chitobiose was
determined. We identified three mutations with a beneficial effect on TG
activity: Y28A (affecting the -1 subsite and the intermediate), Y222A (affecting
the intermediate), and Y226W (affecting the +2 subsite). Furthermore, exchange of
D151, the middle residue in the catalytically important DXDXE motif, to
asparagine reduced hydrolytic activity <=99% with a concomitant increase in
apparent TG activity. The combination of mutations yielded even higher degrees of
TG activity. Reactions with the best mutant, SpChiD-D151N/Y226W/Y222A, led to
rapid accumulation of high levels of TG products that remained stable over time.
Importantly, the introduction of analogous mutations at the same positions in
SmChiA (Y163A equal to Y28A and Y390F similar to Y222A) had similar effects on TG
efficiency. Thus, the combination of the decreasing hydrolytic power, subsite
affinity, and stability of intermediate states provides a powerful, general
strategy for creating hypertransglycosylating mutants of retaining glycoside
hydrolases.
PMID- 29939725
TI - Nickel-Based Membrane Electrodes Enable High-Rate Electrochemical Ammonia
Recovery.
AB - Wastewater contains significant amounts of nitrogen that can be recovered and
valorized as fertilizers and chemicals. This study presents a new membrane
electrode coupled with microbial electrolysis that demonstrates very efficient
ammonia recovery from synthetic centrate. The process utilizes the electrical
potential across electrodes to drive NH4+ ions toward the hydrophilic nickel top
layer on a gas-stripping membrane cathode, which takes advantage of surface pH
increase to realize spontaneous NH3 production and separation. Compared with a
control configuration with conventionally separated electrode and hydrophobic
membrane, the integrated membrane electrode showed 40% higher NH3-N recovery rate
(36.2 +/- 1.2 gNH3-N/m2/d) and 11% higher current density. The energy consumption
was 1.61 +/- 0.03 kWh/kgNH3-N, which was 20% lower than the control and 70-90%
more efficient than competing electrochemical nitrogen recovery processes (5-12
kWh/kgNH3-N). Besides, the negative potential on membrane electrode repelled
negatively charged organics and microbes thus reduced fouling. In addition to
describing the system's performance, we explored the underlying mechanisms
governing the reactions, which confirmed the viability of this process for
efficient wastewater-ammonia recovery. Furthermore, the nickel-based membrane
electrode showed excellent water entry pressure (~41 kPa) without leakage, which
was much higher than that of PTFE/PDMS-based cathodes (~1.8 kPa). The membrane
electrode also showed superb flexibility (180 degrees bend) and can be easily
fabricated at low cost (<20 $/m2).
PMID- 29939726
TI - Insights into the Structures of Superoxide Reductases from the Symbionts
Ignicoccus hospitalis and Nanoarchaeum equitans.
AB - Superoxide reductases (SORs) are enzymes that detoxify the superoxide anion
through its reduction to hydrogen peroxide and exist in both prokaryotes and
eukaryotes. The substrate is transformed at an iron catalytic center,
pentacoordinated in the ferrous state by four histidines and one cysteine. SORs
have a highly conserved motif, (E)(K)HxP-, in which the glutamate is associated
with a redox-driven structural change, completing the octahedral coordination of
the iron in the ferric state, whereas the lysine may be responsible for
stabilization and donation of a proton to catalytic intermediates. We aimed to
understand at the structural level the role of these two residues, by determining
the X-ray structures of the SORs from the hyperthermophilic archaea Ignicoccus
hospitalis and Nanoarchaeum equitans that lack the quasi-conserved lysine and
glutamate, respectively, but have catalytic rate constants similar to those of
the canonical enzymes, as we previously demonstrated. Furthermore, we have
determined the crystal structure of the E23A mutant of I. hospitalis SOR, which
mimics several enzymes that lack both residues. The structures revealed distinct
structural arrangements of the catalytic center that simulate several catalytic
cycle intermediates, namely, the reduced and the oxidized forms, and the
glutamate-free and deprotonated ferric forms. Moreover, the structure of the I.
hospitalis SOR provides evidence for the presence of an alternative lysine close
to the iron center in the reduced state that may be a functional substitute for
the "canonical" lysine.
PMID- 29939727
TI - Cellular Uptake Kinetics of Neutral and Charged Chemicals in in Vitro Assays
Measured by Fluorescence Microscopy.
AB - Cellular uptake kinetics are key for understanding time-dependent chemical
exposure in in vitro cell assays. Slow cellular uptake kinetics in relation to
the total exposure time can considerably reduce the biologically effective dose.
In this study, fluorescence microscopy combined with automated image analysis was
applied for time-resolved quantification of cellular uptake of 10 neutral,
anionic, cationic, and zwitterionic fluorophores in two reporter gene assays. The
chemical fluorescence in the medium remained relatively constant during the 24-h
assay duration, emphasizing that the proteins and lipids in the fetal bovine
serum (FBS) supplemented to the assay medium represent a large reservoir of
reversibly bound chemicals with the potential to compensate for chemical
depletion by cell uptake, growth, and sorption to well materials. Hence FBS plays
a role in stabilizing the cellular dose in a similar way as polymer-based passive
dosing, here we term this process as serum-mediated passive dosing (SMPD).
Neutral chemicals accumulated in the cells up to 12 times faster than charged
chemicals. Increasing medium FBS concentrations accelerated uptake due to FBS
facilitated transport but led to lower cellular concentrations as a result of
increased sorption to medium proteins and lipids. In vitro cell exposure results
from the interaction of several extra- and intracellular processes, leading to
variable and time-dependent exposure between different chemicals and assay
setups. The medium FBS plays a crucial role for the thermodynamic equilibria as
well as for the cellular uptake kinetics, hence influencing exposure. However,
quantification of cellular exposure by an area under the curve (AUC) analysis
illustrated that, for the evaluated bioassay setup, current in vitro exposure
models that assume instantaneous equilibrium between medium and cells still
reflect a realistic exposure because the AUC was typically reduced less than 20%
compared to the cellular dose that would result from instantaneous equilibrium.
PMID- 29939728
TI - Light-Activated Electron Transfer and Turnover in Ru-Modified Aldehyde
Deformylating Oxygenases.
AB - Conversion of biological molecules into fuels or other useful chemicals is an
ongoing chemical challenge. One class of enzymes that has received attention for
such applications is aldehyde deformylating oxygenase (ADO) enzymes. These
enzymes convert aliphatic aldehydes to the alkanes and formate. In this work, we
prepared and investigated ADO enzymes modified with RuII(tris-diimine)
photosensitizers as a starting point for probing intramolecular electron transfer
events. Three variants were prepared, with RuII-modification at the wild type
(WT) residue C70, at the R62C site in one mutant ADO, and at both C62 and C70 in
a second mutant ADO protein. The single-site modification of WT ADO at C70 using
a cysteine-reactive label is an important observation and opens a way forward for
new studies of electron flow, mechanism, and redox catalysis in ADO. These Ru-ADO
constructs can perform the ADO catalytic cycle in the presence of light and a
sacrificial reductant. In this work, the Ru photosensitizer serves as a tethered,
artificial reductase that promotes turnover of aldehyde substrates with different
carbon chain lengths. Peroxide side products were detected for shorter chain
aldehydes, concomitant with less productive turnover. Analysis using
semiclassical electron transfer theory supports proposals for hopping pathway for
electron flow in WT ADO and in our new Ru-ADO proteins.
PMID- 29939729
TI - Irradiation Temperature Dependence of the Photomagnetic Mechanisms in a Cyanido
Bridged CuII2MoIV Trinuclear Molecule.
AB - We report a new bimetallic cyanido-bridged trinuclear complex
[CuII(enpnen)]2[MoIV(CN)8].6.75H2O (1) (enpnen = N,N'-bis(2-aminoethyl)-1,3
propanediamine) that shows reversible photomagnetic effect. The photo-induced
increase of magnetization is characterized by the irradiation temperature
dependent shapes of the chiM T( T) plots and different magnetization values at
low temperature in high magnetic field, suggesting multiple photoexcited states.
The photomagnetic effect in 1 is explained through two possible processes
simultaneously: the light-induced metal-to-metal charge transfer (MMCT) in the
CuII-NC-MoIV pair and the light-induced excited spin-state trapping (LIESST)
effect in MoIV center. A numerical model assuming the simultaneous existence of
three possible states after irradiation: the MMCT CuI-NC-MoV-CN-CuII state, the
LIESST CuII-NC-MoIVHS-CN-CuII state, and the ground-state CuII-NC-MoIVLS-CN-CuII
was applied to the data and resulted in Cu-Mo exchange coupling constants J1MMCT
= 11 cm-1 and J2LIESST = 109 cm-1 for the MMCT and LIESST mechanisms induced
states, respectively. Fractions of respective states after irradiations at
different temperatures were also calculated, shedding light on the influence of
irradiation temperature on the photomagnetic mechanism. The proposed model can
provide the interpretative framework for testing and refinement of the mechanism
of photomagnetic effect in other coordination networks with cyanido-bridged Cu
[Mo(CN)8]4- linkages.
PMID- 29939730
TI - Oxidation of the 14-Membered Macrocycle Dibenzotetramethyltetraaza[14]annulene
upon Ligation to the Uranyl Ion.
AB - Reaction of Li2(tmtaa) (tmtaaH2 = dibenzotetramethyltetraaza[14]annulene) with 1
equiv of [UO2Cl2(THF)3], in an attempt to form cis-[UO2(tmtaa)], affords the
bis(uranyl) complex [Li(THF)3][Li(THF)2][(UO2Cl2)2(tmtaa)] (1) as a red-brown
crystalline solid in modest yield. Complex 1 can be synthesized rationally by
reaction of Li2(tmtaa) with 2 equiv of [UO2Cl2(THF)3]. Under these conditions, it
can be isolated in 44% yield. In the solid state, complex 1 features two [UO2Cl2]
fragments that are bridged by a highly puckered (tmtaa)2- ligand. Both uranyl
fragments feature normal uranyl metrical parameters (U-O (av.) = 1.78 A, O-U-O =
176.8(3) degrees and 178.0(3) degrees ). The most notable structural feature of
1, however, is the presence of a lithium cation that coordinates to an oxo ligand
from each uranyl fragment. In contrast to the Li2(tmtaa) reaction, addition of
[K(DME)]2[tmtaa] to 1 equiv of [UO2Cl2(THF)3] results in formation of the 2e-
oxidation products of (tmtaa)2-. Three isomers of C22H22N4 (compounds 2, 3, and
4) were isolated as a mixture of orange crystals in 41% combined yield. All three
isomers were characterized by X-ray crystallography. We hypothesize that these
ligand oxidation products are formed upon decomposition of the unobserved cis
uranyl intermediate, cis-[UO2(tmtaa)], which undergoes a facile intramolecular
redox reaction.
PMID- 29939731
TI - Stereoisomer-Specific Trophodynamics of the Chiral Brominated Flame Retardants
HBCD and TBECH in a Marine Food Web, with Implications for Human Exposure.
AB - Stereoisomers of 1,2,5,6,9,10-hexabromocyclododecane (HBCD) and 1,2-dibromo-4
(1,2-dibromoethyl)-cyclohexane (TBECH) were determined in sediments and 30 marine
species in a marine food web to investigate their trophic transfer. Lipid content
was found to affect the bioaccumulation of SigmaHBCD and SigmaTBECH in these
species. Elevated biomagnification of each diastereomer from prey species to
marine mammals was observed. For HBCD, biota samples showed a shift from gamma-
to alpha-HBCD when compared with sediments and technical mixtures; trophic
magnification potential of (-)-alpha- and (+)-alpha-HBCD were observed in the
food web, with trophic magnification factors (TMFs) of 11.8 and 8.7,
respectively. For TBECH, the relative abundance of gamma- and delta-TBECH
exhibited an increasing trend from abiotic matrices to biota samples; trophic
magnification was observed for each diastereomer, with TMFs ranging from 1.9 to
3.5. The enantioselective bioaccumulation of the first eluting enantiomer of
delta-TBECH in organisms at higher TLs was consistently observed across samples.
This is the first report on the trophic transfer of TBECH in the food web. The
estimated daily intake of HBCD for Hong Kong residents was approximately 16-times
higher than that for the general population in China, and the health risk to
local children was high, based on the relevant available reference dose.
PMID- 29939732
TI - Fluid Flow Model for Predicting the Intrusion Rate of Subsurface Contaminant
Vapors into Buildings.
AB - A new method is presented for calculating a building-specific subslab to indoor
air attenuation factor for use in assessing subsurface vapor intrusion to indoor
air. The technique includes (1) subslab gas extraction with flow and vacuum
measurements and mathematical modeling to characterize the bulk average vertical
gas conductivity of the floor slab, (2) monitoring of the ambient pressure
gradient across the floor slab with a micromanometer, (3) calculating the
volumetric flow of soil gas into the building ( Qsoil), and (4) dividing Qsoil by
the building ventilation rate ( Qbuilding) to calculate a building-specific
attenuation factor. Sample calculations using order statistics from 121
individual tests are comparable to the U.S. Environmental Protection Agency
empirical attenuation factors for residential buildings and the U.S. Navy
empirical attenuation factors for commercial/industrial buildings. A case study
of a commercial building shows encouraging agreement between the attenuation
factors calculated via this method and via conventional subslab and indoor air
sampling.
PMID- 29939733
TI - Metal-Coordination-Induced Fusion Creates Hollow Crystalline Molecular
Superstructures.
AB - In this work, we report the formation of superstructures assembled from organic
tubular crystals mediated by metal-coordination chemistry. This template-free
process involves the crystallization of molecules into crystals having a
rectangular and uniform morphology, which then go on to fuse together into
multibranched superstructures. The initially hollow and organic crystals are
obtained under solvothermal conditions in the presence of a copper salt, whereas
the superstructures are subsequently formed by aging the reaction mixture at room
temperature. The mild thermodynamic conditions and the favorable kinetics of this
unique self-assembly process allowed us to ex-situ monitor the superstructure
formation by electron microscopy, highlighting a pivotal and unusual role for
copper ions in their formation and stabilization.
PMID- 29939734
TI - Influence of Plasmonic Effect on the Upconversion Emission Characteristics of
NaYF4 Hexagonal Microrods.
AB - The influence of plasmonic effect on the upconversion emission characteristics of
Yb3+-Er3+-Tm3+ tridoped beta-NaYF4 hexagonal microrods is studied. Upconversion
spontaneous emission can be improved by 10 times if the microrod is deposited on
an Ag-coated substrate. The enhancement is also dependent on the emission
wavelength and the polarization of the excitation source. Furthermore,
upconversion lasing is supported by the geometry of the microrods via the
formation of whispering gallery modes. The corresponding excitation threshold can
also be reduced by 50% through the influence of plasmonic effect, the coupling
between the whispering gallery modes and the surface plasmonic resonance modes.
PMID- 29939735
TI - Tetra-, Hexa-, Dodeca-Nuclear Ir Supramolecules via Bridge-Driven Self-Assembly
of Tetrazolyl Ligands.
AB - Herein, we report the formation of multinuclear Ir4, Ir6, and Ir12 supramolecular
complexes via the bridge-driven self-assembly of tetrazolyl ligands. The
synthesis of dimeric half-sandwich Ir units was made by the reaction of half
sandwich Ir units and tetrazolyl ligands in a molar ratio of 1:2. The use of
different ligands containing multiple tetrazolyl units resulted in the formation
of different Ir supramolecular architectures. The reaction of [Cp*IrCl2]2, AgOTf,
and 1,2- or 1,3-ditetrazolyl benzene in a molar ratio of 1:3:1 resulted in the
formation of rectangular tetranuclear or truncated trigonal pyramidal hexanuclear
Ir complexes, respectively. On the other hand, the reaction of [Cp*IrCl2]2,
AgOTf, and 1,3,5-tritetrazolyl benzene in a molar ratio of 6:18:4 produced a
supramolecular dodecanuclear iridium complex. The molecular structure of the
complex resembled a truncated tetrahedral structure with a large inner cavity, as
determined by X-ray crystallography.
PMID- 29939736
TI - Low-Spin Fe(III) Macrocyclic Complexes of Imidazole-Appended 1,4,7
Triazacyclononane as Paramagnetic Probes.
AB - Two macrocyclic complexes of 1,4,7-triazacyclononane (TACN), one with N-methyl
imidazole pendants, [Fe(Mim)]3+, and one with unsubstituted NH imidazole
pendants, [Fe(Tim)]3+, were prepared with a view toward biomedical imaging
applications. These low-spin Fe3+ complexes produce moderately paramagnetically
shifted and relatively sharp 1H NMR resonances for paraSHIFT and paraCEST
applications. The [Fe(Tim)]3+ complex undergoes pH-dependent changes in NMR
spectra in solution that are consistent with the consecutive deprotonation of all
three imidazole pendant groups at high pH values. N-Methylation of the imidazole
pendants in [Fe(Mim)]3+ produces a complex that dissociates more readily at high
pH in comparison to [Fe(Tim)]3+, which contains ionizable donor groups. Cyclic
voltammetry studies show that the redox potential of [Fe(Mim)]3+ is invariant
with pH ( E1/2 = 328 +/- 3 mV vs NHE) between pH 3.2 and 8.4, unlike the Fe(III)
complex of Tim which shows a 590 mV change in redox potential over the pH range
of 3.3-12.8. Magnetic susceptibility studies in solution give magnetic moments of
0.91-1.3 cm3 K mol-1 (MUeff value = 2.7-3.2) for both complexes. Solid-state
measurements show that the susceptibility is consistent with a S = 1/2 state over
the temperature range of 0 to 300 K, with no crossover to a high-spin state under
these conditions. The crystal structure of [Fe(Mim)](OTf)3 shows a six-coordinate
all-nitrogen bound Fe(III) in a distorted octahedral environment. Relativistic ab
initio wave function and density functional theory (DFT) calculations on
[Fe(Mim)]3+, some with spin orbit coupling, were used to predict the ground spin
state. Relative energies of the doublet, quartet, and sextet spin states were
consistent with the doublet S = 1/2 state being the lowest in energy and
suggested that excited states with higher spin multiplicities are not thermally
accessible. Calculations were consistent with the magnetic susceptibility
determined in the solid state.
PMID- 29939737
TI - A New Fluorogenic Small-Molecule Labeling Tool for Surface Diffusion Analysis and
Advanced Fluorescence Imaging of beta-Site Amyloid Precursor Protein-Cleaving
Enzyme 1 Based on Silicone Rhodamine: SiR-BACE1.
AB - beta-site APP-cleaving enzyme 1 (BACE1) is a major player in the pathogenesis of
Alzheimer's disease. Structural and functional fluorescence microscopy offers a
powerful approach to learn about the physiology and pathophysiology of this
protease. Up to now, however, common labeling techniques require genetic
manipulation, use large antibodies, or are not compatible with live cell imaging.
Fluorescent small molecules that specifically bind to the protein of interest can
overcome these limitations. Herein, we introduce SiR-BACE1, a conjugate of the
BACE1 inhibitor S-39 and SiR647, as a novel fluorogenic, tag-free, and antibody
free label for BACE1. We present its chemical development, characterize its
photophysical and pharmacologic properties, and evaluate its behavior in
solution, in overexpression systems, and in native brain tissue. We demonstrate
its applicability in confocal, stimulated emission depletion and dynamic single
molecule microscopy. The first functional studies with SiR-BACE1 on the surface
mobility of BACE1 revealed a markedly confined diffusion pattern.
PMID- 29939738
TI - Thermochemical and Kinetics of the CH3OH + (4S)N Reactional System.
AB - The reaction of methanol (CH3OH) with atomic nitrogen was studied considering
three elementary reactions, the hydrogen abstractions from the hydroxyl or methyl
groups (R1 and R3, respectively) and the C-O bond break (R2). Thermochemical
properties were obtained using ab initio methods and density functional theory
approximations with aug-cc-pVXZ (X = T and Q) basis sets. The minimum energy path
was built with a dual-level methodology using the BB1K functional as the low
level and the CCSD(T) as the high-level. This surface was used to calculate the
thermal rate constants in the frame of variational transitional state theory
considering the tunneling effects. Our results indicate the dehydrogenation of
the methyl group (R3) as the dominant path with k R3 = 7.5 * 10-27 cm3.molecule
1.s-1 at 300 K. The thermal rate constants were fitted to a modified Arrhenius
equation for use in mechanism studies of the methanol decomposition.
PMID- 29939739
TI - Impact of the Keto-Enol Tautomeric Equilibrium on the BODIPY Chromophore.
AB - An intramolecular tautomeric fluorescent BODIPY sensor has been designed and
synthesized. The obtained BODIPY dye is a combination of the 4-bora- 3a, 4a-diaza
s-indacene core and a diketone fragment. The study of conformational equilibria
in the ground and excited states has been completed for a broad range of solvent
polarity by steady state and NMR methods as well as by DFT and TD-DFT
calculations. The interpretation of the unique emission observed in hydrogen bond
accepting solvents upon the excitation of the fluorescent dye in the S0-S2
transition has been accomplished. The Jablonski diagram has been analyzed for the
observed processes in the BODIPY dye studied on the basis of DFT and TD-DFT
calculations.
PMID- 29939741
TI - Linfuranones B and C, Furanone-Containing Polyketides from a Plant-Associated
Sphaerimonospora mesophila.
AB - Two new furanone-containing polyketides, linfuranones B and C, were isolated from
a plant-associated actinomycete of the genus Sphaerimonospora. Their structures
were determined by NMR and MS spectroscopic analyses, and the absolute
configurations were established by anisotropic methods and chemical degradation
approaches. In silico analysis of biosynthetic genes suggested that linfuranone B
is generated from linfuranone C by oxidative cleavage of the polyketide chain.
Linfuranones B and C induced preadipocyte differentiation into matured adipocytes
at 20-40 MUM without showing cytotoxicity.
PMID- 29939740
TI - Efficient alpha-Glucosylation of Epigallocatechin Gallate Catalyzed by
Cyclodextrin Glucanotransferase from Thermoanaerobacter Species.
AB - The glycosylation of plant polyphenols may modulate their solubility and
bioavailability and protect these molecules from oxygen, light degradation, and
during gastrointestinal transit. In this work, the synthesis of various alpha
glucosyl derivatives of (-)-epigallocatechin gallate, the predominant catechin in
green tea, was performed in water at 50 degrees C by a transglycosylation
reaction catalyzed by cyclodextrin glycosyltransferase from Thermoanaerobacter
sp. The molecular weight of reaction products was determined by high-performance
liquid chromatography coupled to mass spectrometry. Using hydrolyzed potato
starch as a glucosyl donor, two main monoglucosides were obtained with conversion
yields of 58 and 13%, respectively. The products were isolated and chemically
characterized by combining two-dimensional nuclear magnetic resonance methods.
The major derivative was epigallocatechin gallate 3'- O-alpha-d-glucopyranoside
(1), and the minor derivative was epigallocatechin gallate 7- O-alpha-d
glucopyranoside (2).
PMID- 29939742
TI - Targeting Myeloid Differentiation Using Potent 2-Hydroxypyrazolo[1,5- a]pyridine
Scaffold-Based Human Dihydroorotate Dehydrogenase Inhibitors.
AB - Human dihydroorotate dehydrogenase ( hDHODH) catalyzes the rate-limiting step in
de novo pyrimidine biosynthesis, the conversion of dihydroorotate to orotate.
hDHODH has recently been found to be associated with acute myelogenous leukemia,
a disease for which the standard of intensive care has not changed over decades.
This work presents a novel class of hDHODH inhibitors, which are based on an
unusual carboxylic group bioisostere 2-hydroxypyrazolo[1,5- a]pyridine, that has
been designed starting from brequinar, one of the most potent hDHODH inhibitors.
A combination of structure-based and ligand-based strategies produced compound 4,
which shows brequinar-like hDHODH potency in vitro and is superior in terms of
cytotoxicity and immunosuppression. Compound 4 also restores myeloid
differentiation in leukemia cell lines at concentrations that are one log digit
lower than those achieved in experiments with brequinar. This Article reports the
design, synthesis, SAR, X-ray crystallography, biological assays, and
physicochemical characterization of the new class of hDHODH inhibitors.
PMID- 29939743
TI - Ultrafast Raman Loss Spectroscopy Unravels the Dynamics in Entangled Singlet and
Triplet States in Thioxanthone.
AB - Thioxanthone (TX), an aromatic ketone, exhibits significant solvent-dependent
photophysical properties. Herein, we employed time-resolved ultrafast Raman loss
spectroscopy (URLS) to decipher the solvent-dependent structural dynamics in
entangled singlet and triplet states of photoexcited TX. The evolution of the
vibrational spectrum reveals structural changes that occur during the intersystem
crossing (ISC) process and the subsequent energy dissipation to the surrounding
solvent. The C?O stretch (~1320 cm-1) of TX in the excited state acts as the
marker band as it undergoes a red shift with time constants of ~45 and ~5 ps in
acetonitrile and methanol, respectively. Such a red shift is an indicator of the
softening of the bond due to the change in the electronic spin states. We also
observed a blue shift in Raman frequencies corresponding to the C?C stretch and
the C?O stretching modes of TX in acetonitrile and methanol, indicating
vibrational cooling in the excited singlet and triplet states. In the case of TX
in cyclohexane, vibrational modes at 190 and 415 cm-1 exhibit a blue shift with a
time constant of ~700 fs, which represents the structural distortion during
internal conversion (S2 -> S1) process. The kinetics of amplitudes of these modes
follows biexponential growth with time constants of ~3 and ~14 ps representing
the time scales for the ISC process and the planarization process in the triplet
state, respectively. The URLS study therefore provides a direct measure of the
various stages of the solvent-dependent structural dynamics in the excited state
of TX.
PMID- 29939744
TI - Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional
Selectivity Relationships (SFSRs) and Therapeutic Potential.
AB - G protein-coupled receptors (GPCRs) signal through both G-protein-dependent and G
protein-independent pathways, and beta-arrestin recruitment is the most
recognized one of the latter. Biased ligands selective for either pathway are
expected to regulate biological functions of GPCRs in a more precise way,
therefore providing new drug molecules with superior efficacy and/or reduced side
effects. During the past decade, biased ligands have been discovered and
developed for many GPCRs, such as the MU opioid receptor, the angiotensin II
receptor type 1, the dopamine D2 receptor, and many others. In this Perspective,
recent advances in this field are reviewed by discussing the structure-functional
selectivity relationships (SFSRs) of GPCR biased ligands and the therapeutic
potential of these molecules. Further understanding of the biological functions
associated with each signaling pathway and structural basis for biased signaling
will facilitate future drug design in this field.
PMID- 29939745
TI - Excited State Decay Pathways of 2'-Deoxy-5-methylcytidine and Deoxycytidine
Revisited in Solution: A Comprehensive Kinetic Study by Femtosecond Transient
Absorption.
AB - Methylated cytosine is proved to have an important role as an epigenetic signal
in gene regulation and is often referred to "the fifth base of DNA". A
comprehensive understanding of the electronic excited state relaxation in
cytosine and its methylated derivatives is crucial for revealing UV-induced
photodamage to the biological genome. Because of the existence of multiple
closely lying "bright" and "dark" excited states, the decay pathways in these DNA
nucleosides are the most complex and the least understood so far. In this study,
femtosecond transient absorption with different excitation wavelengths (240-296
nm) was used to study the relaxation of excited electronic states of 5
methylcytosine (5mC) and 2'-deoxy-5-methylcytidine (5mdCyd) in phosphate buffered
aqueous solution and in acetonitrile solution. Two distinct nonradiative decay
channels were directly observed. The first one is a several picosecond internal
conversion channel that involves two bright pipi* states (pipi*2 and pipi*1) when
pipi*2 state is initially populated. The second channel contains the lower energy
pipi*1 state and a so far experimental unidentified long-lived state which
exhibits a several nanosecond lifetime. The long-lived state can only be accessed
by the initially excited pipi*1 state. Inspired by this new discovery in 5mC and
5mdCyd, we revisited the decay of excited state of 2'-deoxycytidine (dCyd),
revealing very similar decay pathways. Additionally, a well-known dark nOpi*
state (carbonyl lone pair) with ~30 ps lifetime is present in both decay channels
in dCyd. With our detailed experimental results, we successfully reconcile the
long history debate of cytosine excited state relaxation mechanism by pointing
out that the reason for the complex dynamics under traditional 266 nm excitation
is mixed signals from the above-mentioned two distinct decay pathways. Our
findings lead to a dramatically different and new picture of electronic energy
relaxation in 5mdCyd/dCyd and could help to understand photostability as well as
UV-induced photodamage of these nucleotides and related DNAs.
PMID- 29939746
TI - Synthesis and Evaluation of a Novel Bivalent Selective Antagonist for the Mu
Delta Opioid Receptor Heterodimer that Reduces Morphine Withdrawal in Mice.
AB - A major limitation in the study of the mu-delta opioid receptor heterodimer
(MDOR) is that few selective pharmacological tools exist and no heteromer
selective antagonists. We thus designed a series of variable-length (15-41 atoms)
bivalent linked peptides with selective but moderate/low-affinity pharmacophores
for the mu and delta opioid receptors. We observed a U-shaped MDOR
potency/affinity profile in vitro, with the 24-atom spacer length (D24M)
producing the highest MDOR potency/affinity (<1 nM) and selectivity (>=89-fold).
We further evaluated D24M in mice and observed that D24M dose-dependently
antagonized tail flick antinociception produced by the MDOR agonists CYM51010 and
Deltorphin-II, without antagonizing the monomer agonists DAMGO and DSLET. We also
observed that D24M sharply reduced withdrawal behavior in models of acute and
chronic morphine dependence. These findings suggest that D24M is a first-in-class
high-potency MDOR-selective antagonist both in vitro and in vivo.
PMID- 29939747
TI - Merging In-Solution X-ray and Neutron Scattering Data Allows Fine Structural
Analysis of Membrane-Protein Detergent Complexes.
AB - In-solution small-angle X-ray and neutron scattering (SAXS/SANS) have become
popular methods to characterize the structure of membrane proteins, solubilized
by either detergents or nanodiscs. SANS studies of protein-detergent complexes
usually require deuterium-labeled proteins or detergents, which in turn often
lead to problems in their expression or purification. Here, we report an approach
whose novelty is the combined analysis of SAXS and SANS data from an unlabeled
membrane protein complex in solution in two complementary ways. First, an
explicit atomic analysis, including both protein and detergent molecules, using
the program WAXSiS, which has been adapted to predict SANS data. Second, the use
of MONSA which allows one to discriminate between detergent head- and tail-groups
in an ab initio approach. Our approach is readily applicable to any detergent
solubilized protein and provides more detailed structural information on protein
detergent complexes from unlabeled samples than SAXS or SANS alone.
PMID- 29939748
TI - Synthesis and Porous SiO2 Nanofilm Formation of the Silsesquioxane-Containing
Amphiphilic Block Copolymer.
AB - We describe the synthesis, Langmuir-Blodgett (LB) film formation, and photo
oxidation of an organic-inorganic hybrid block copolymer consisting of N-dodecyl
acrylamide (DDA) and silsesquioxane (SQ) comonomers [p(DDA/SQ26)- b-pDDA]. The
copolymer was synthesized by reversible addition fragmentation chain transfer
polymerization of DDA and SQ. Higher monolayer stability at the air-water
interface was confirmed for p(DDA/SQ26)- b-pDDA. The p(DDA/SQ26)- b-pDDA
monolayer was deposited onto solid substrates with a monolayer thickness of 2.3
nm. The photo-oxidized SiO2 nanofilm revealed its porous structure, which
reflects phase-separated structures of p(DDA/SQ26)- b-pDDA, as confirmed using
atomic force microscopy, quartz crystal microbalance, and cyclic voltammetry
measurements. These results demonstrate that this preparation method using photo
oxidation of the organic-inorganic hybrid block copolymer LB film is promising
for manipulating pore formations of inorganic oxide nanofilms.
PMID- 29939749
TI - Biluminescence via Fluorescence and Persistent Phosphorescence in Amorphous
Organic Donor(D4)-Acceptor(A) Conjugates and Application in Data Security
Protection.
AB - Purely organic biluminescent materials are of great interest due to the
involvement of both singlet and long-lived triplet emissions, which have been
rarely reported in bioimaging and organic light-emitting diodes. We show two
molecules 3,4,5,6-tetraphenyloxy-phthalonitrile (POP) and 3,4,5,6-tetrakis- p
tolyloxy-phthalonitrile (TOP), in which POP was found to exhibit fluorescence and
persistent room-temperature green phosphorescence (pRTGP) in the amorphous powder
and crystal states. Both POP and TOP show aggregation-induced emission in a
tetrahydrofuran-water mixture. We found in single-crystal X-ray analysis that
intra- and intermolecular lp(O)...pi interactions along with pi(C = C)...pi(C=N),
hydrogen bond (H-B), and C-H...pi interactions induce a head-to-tail slipped
stack arrangement in POP. In addition, the X-ray structure of TOP with a slipped
stack arrangement induced by only pi(C?C)...pi(C=N) and H-B interactions shows
dim afterglow only in crystals. These indicate that more noncovalent interactions
found in POP may reinforce relatively efficient intersystem crossing that leads
to pRTGP. Given the unique green afterglow feature in amorphous powder of POP,
document security protection application is achievable.
PMID- 29939752
TI - Graphene Translucency and Interfacial Interactions in the Gold/Graphene/SiC
System.
AB - Integration of graphene into electronic circuits through its joining with
conventional metal electrodes (i.e., gold) appears to be one of the main
technological challenges nowadays. To gain insight into this junction, we have
studied the physicochemical interactions between SiC-supported graphene and a
drop of molten gold. Using appropriate high-temperature experimental conditions,
we perform wetting experiments and determine contact angles for gold drops
supported on graphene epitaxially grown on 4H-SiC. The properties of the
metal/graphene interface are analyzed using a wide variety of characterization
techniques, along with computational simulations based on density functional
theory. In contrast with the established literature, our outcomes clearly show
that graphene is translucent in the gold/graphene/SiC interface, and therefore
its integration into electronic circuits primarily depends on the right choice of
the support to produce favorable wetting interactions with liquid gold.
PMID- 29939750
TI - Redox-Annulations of Cyclic Amines with 2-(2-Oxoethyl)malonates.
AB - Amines such as 1,2,3,4-tetrahydroisoquinoline undergo redox-neutral annulations
with 2-(2-oxoethyl)malonates in the presence of catalytic amounts of benzoic
acid. These reactions install a fully saturated five-membered ring and provide
access to structures closely related to the natural products crispine A and
harmicine.
PMID- 29939751
TI - Single, Double Electronic Excitations and Exciton Effective Conjugation Lengths
in pi-Conjugated Systems.
AB - The 21Ag and 11Bu excited states of two prototypical pi-conjugated compounds,
polyacetylene and polydiacetylene, are investigated with the recently developed
particle-particle random phase approximation (pp-RPA) method combined with the
B3LYP functional. The polymer-limit transition energies are estimated as 1.38 and
1.72 eV for the 21Ag and 11Bu states, respectively, from an extrapolation of the
computed excitation energies of model oligomers. These values increase to 1.95
and 2.24 eV for the same transitions when ground-state structures with ~33%
larger bond length alternation are adopted. Applying the pp-RPA to the vertical
excitation energies in oligodiacetylene, the polymer-limit transition energies of
the 21Ag and 11Bu states are computed to be 2.06 and 2.28 eV, respectively. These
results are in good agreement with experimental values or theoretical best
estimates, indicating that the pp-RPA method shows great promise for
understanding many photophysical phenomena involving both single and double
excitations.
PMID- 29939753
TI - Insight into Water-Soluble Highly Fluorescent Low-Dimensional Host-Guest
Supramolecular Polymers: Structure and Energy-Transfer Dynamics Revealed by
Polarized Fluorescence Spectroscopy.
AB - Water-soluble, highly fluorescent host-guest chromophore-cucurbit[8]uril
supramolecular polymer bundles are investigated by polarized time-resolved
photoluminescence spectroscopy, structural methods, and quantum chemistry to
fully reveal structural organization and heterogeneity but, in particular, energy
transfer dynamics, being of crucial importance for the design of supramolecular
artificial light-harvesting systems.
PMID- 29939754
TI - Thiol-Ene Alginate Hydrogels as Versatile Bioinks for Bioprinting.
AB - Bioprinting is a powerful technique that allows precise and controlled 3D
deposition of biomaterials in a predesigned, customizable, and reproducible
manner. Cell-laden hydrogel ("bioink") bioprinting is especially advantageous for
tissue engineering applications as multiple cells and biomaterial compositions
can be selectively dispensed to create spatially well-defined architectures.
Despite this promise, few hydrogel systems are easily available and suitable as
bioinks, with even fewer systems allowing for molecular design of mechanical and
biological properties. In this study, we report the development of a norbornene
functionalized alginate system as a cell-laden bioink for extrusion-based
bioprinting, with a rapid UV-induced thiol-ene cross-linking mechanism that
avoids acrylate kinetic chain formation. The mechanical and swelling properties
of the hydrogels are tunable by varying the concentration, length, and structure
of dithiol PEG cross-linkers and can be further modified by postprinting
secondary cross-linking with divalent ions such as calcium. The low
concentrations of alginate needed (<2 wt %), coupled with their rapid in situ
gelation, allow both the maintenance of high cell viability and the ability to
fabricate large multilayer or multibioink constructs with identical bioprinting
conditions. The modularity of this bioink platform design enables not only the
rational design of materials properties but also the gel's biofunctionality (as
shown via RGD attachment) for the expected tissue-engineering application. This
modularity enables the creation of multizonal and multicellular constructs
utilizing a chemically similar bioink platform. Such tailorable bioink platforms
will enable increased complexity in 3D bioprinted constructs.
PMID- 29939755
TI - A Glutamine-Rich Carrier Efficiently Delivers Anti-CD47 siRNA Driven by a
"Glutamine Trap" To Inhibit Lung Cancer Cell Growth.
AB - It is not efficient enough using the current approaches for tumor-selective drug
delivery based on the EPR effect and ligand-receptor interactions, and they have
largely failed to translate into the clinic. Therefore, it is urgent to explore
an enhanced strategy for effective delivery of anticancer agents. Clinically,
many cancers require large amounts of glutamine for their continued growth and
survival, resulting in circulating glutamine extraction by the tumor being much
greater than that for any organs, behaving as a "glutamine trap". In the present
study, we sought to elucidate whether the glutamine-trap effect could be
exploited to deliver therapeutic agents to selectively kill cancer cells. Here, a
macromolecular glutamine analogue, glutamine-functionalized branched
polyethylenimine (GPI), was constructed as the carrier to deliver anti-CD47 siRNA
for the blockage of CD47 "don't eat me" signals on cancer cells. The GPI/siRNA
glutamine-rich polyplexes exhibited remarkably high levels of cellular uptake by
glutamine-dependent lung cancer cells, wild-type A549 cells (A549WT), and its
cisplatin-resistant cells (A549DDP), specifically under glutamine-depleted
conditions. It was noted that the glutamine transporter ASCT2 was highly
expressed both on A549WT and A549DDP but with almost no expression in normal
human lung fibroblasts cells. Inhibition of ASCT2 significantly prevented the
internalization of GPI polyplexes. These findings raised the intriguing
possibility that the glutamine-rich GPI polyplexes utilize the ASCT2 pathway to
selectively facilitate their cellular uptake by cancer cells. GPI further
delivered anti-CD47 siRNA efficiently both in vitro and in vivo to downregulate
the intratumoral mRNA and protein expression levels of CD47. CD47 functions as a
"don't eat me" signal and binds to the immunoreceptor SIRPalpha inducing evasion
of phagocytic clearance. GPI/anti-CD47 siRNA polyplexes achieved significant
antitumor activities both on A549WT and A549DDP tumor-bearing nude mice. Notably,
it had no adverse effect on CD47-expressing red blood cells and platelets, likely
because of selective delivery. Therefore, the glutamine-rich carrier GPI driven
by the glutamine-trap effect provides a promising new strategy for designing
anticancer drug delivery systems.
PMID- 29939756
TI - Electrostatics Generated by a Supramolecular Capsule Stabilizes the Transition
State for Carbon-Carbon Reductive Elimination from Gold(III) Complex.
AB - Tetrahedral assemblies of stoichiometry M4L6 have been proven to catalyze a range
of chemical reactions including the carbon-carbon reductive elimination reaction
from transition metals such as gold. Here, we perform quantum chemical
calculations of Gold(III) transition metal complexes in vacuum, and encapsulated
in Ga4L612- or Si4L68- assemblies within both a reaction field continuum solvent
and in an aqueous molecular environment with counterions, to rationalize the rate
enhancements observed experimentally for the reductive elimination reaction. We
find that the Ga4L612- assembly lowers the energy barrier of the reaction
compared to Si4L68-, which is consistent with kinetic trends observed
experimentally. We have determined that the primary factor for catalytic rate
acceleration stems from the electrostatic environment emanating from the Ga4L612-
capsule as opposed to the water or counterions.
PMID- 29939757
TI - Xanthatin Promotes Apoptosis via Inhibiting Thioredoxin Reductase and Eliciting
Oxidative Stress.
AB - Xanthatin (XT), a naturally occurring sesquiterpene lactone presented in
cocklebur ( Xanthium strumarium L.), is under development as a potential
anticancer agent. Despite the promising anticancer effect of XT, the molecular
mechanism underlying its cellular action has not been well elucidated. The
mammalian thioredoxin reductase (TrxR) enzymes, the essential seleno
flavoproteins containing a penultimate selenocysteine (Sec) residue at the C
terminus, represent a promising target for cancer chemotherapeutic agents. In
this study, XT inhibits both the purified TrxR and the enzyme in cells. The
possible binding mode of XT with the TrxR protein is predicted by the covalent
docking method. Mechanism studies reveal that XT targets the Sec residue of TrxR
and inhibits the enzyme activity irreversibly. Simultaneously, the inhibition of
TrxR by XT promotes the oxidative stress-mediated apoptosis of HeLa cells.
Importantly, the knockdown of the enzyme sensitizes the cells to XT treatment.
Targeting TrxR thus discloses a novel molecular mechanism in accounting for the
cellular action of XT and provides insights into the development of XT as an
anticancer agent.
PMID- 29939758
TI - Switchable Selectivity in the Pd-Catalyzed Alkylative Cross-Coupling of Esters.
AB - The Pd-catalyzed cross-coupling of phenyl esters and alkyl boranes is disclosed.
Two reaction modes are rendered accessible in a selective fashion by interchange
of the catalyst. With a Pd-NHC system, alkyl ketones can be prepared in good
yields via a Suzuki-Miyaura reaction proceeding by activation of the C(acyl)-O
bond. Use of a Pd-dcype catalyst enables alkylated arenes to be synthesized by a
modified pathway with extrusion of CO. Applications of this divergent coupling
strategy and the origin of the switchable selectivity are discussed.
PMID- 29939759
TI - Enantiomers of Single-Wall Carbon Nanotubes Show Distinct Coating Displacement
Kinetics.
AB - It is known that specific oligomers of single-stranded DNA (ssDNA) can show
remarkable selectivity when coating different structural species of single-wall
carbon nanotubes (SWCNTs). We report that (ATT)4 ssDNA coatings strongly
distinguish between the two optical isomers of (7,5) SWCNTs. This causes
resolvable shifts in their fluorescence spectra and differences of 2 orders of
magnitude in the room temperature rates of coating displacement, as monitored
through changes in nanotube fluorescence wavelength and intensity on exposure to
sodium deoxycholate. During coating displacement, the enantiomer with high
affinity for the ssDNA oligomer is deduced to form an intermediate hybrid that is
not observed for the low affinity enantiomer. These results reveal that
enantiomeric differences in SWCNTs complexed with ssDNA are more diverse and
dramatic than previously recognized.
PMID- 29939760
TI - Sorting Metal Nanoparticles with Dynamic and Tunable Optical Driven Forces.
AB - Precise sorting of colloidal nanoparticles is a challenging yet necessary task
for size-specific applications of nanoparticles in nanophotonics and
biochemistry. Here we present a new strategy for all-optical sorting of metal
nanoparticles with dynamic and tunable optical driven forces generated by phase
gradients of light. Size-dependent optical forces arising from the phase
gradients of optical line traps can drive nanoparticles of different sizes with
different velocities in solution, leading to their separation along the line
traps. By using a sequential combination of optical lines to create differential
trapping potentials, we realize precise sorting of silver and gold nanoparticles
in the diameter range of 70-150 nm with a resolution down to 10 nm. Separation of
the nanoparticles agrees with the analysis of optical forces acting on them and
with simulations of their kinetic motions. The results provide new insights into
all-optical nanoparticle manipulation and separation and reveal that there is
still room to sort smaller nanoparticle with nanometer precision using dynamic
phase-gradient forces.
PMID- 29939761
TI - A comparison of the cutaneous microvascular properties of the Spontaneously
Hypertensive and the Wistar-Kyoto rats by Spectral analysis of Laser Doppler.
AB - This work was aimed to study skin blood perfusion, vasomotion and vascular
responses of the Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats
(SHR) in different stages of age using spectral. Laser-Doppler flowmetry (LDF)
was used to examine the ears and limbs of WKY (12 and 48 weeks old) and SHR (12
and 48 weeks old). The skin blood flow oscillations (SBFOs) were studied by
wavelet spectral analysis of LDF tracings. Then, we observed that old groups
showed decreased perfusion and SBFO in the ears of both SHR and WKY. The SHR
showed obviously lower postocclusive reactive hypera (PORH) ratio at the same
age. A decreased peak-time occurred in the SHR of old age group. After PORH test,
a statistically significant increase was observed within all subintervals in the
absolute amplitude of 12-week WKY and only within IV and III subintervals in the
absolute amplitude of 12-week SHR. But, the absolute amplitude of 48-week WKY and
SHR showed no statistically significant increase within all subintervals. Results
indicated that local regulating function of peripheral vascular was impaired in
rat with hypertension and aging. Abbreviations LDF: Laser-Doppler flowmetry; SBF:
Skin blood flow; SBFO: Skin blood flow oscillation; PORH: Postocclusive reactive
hyperemia; SHR: Spontaneously hypertensive rats; WKY: Wistar-Kyoto rats; LDF:
Laser-Doppler flowmetry; LDI: Laser Doppler Imaging; BP: Blood pressure.
PMID- 29939762
TI - Swallow and Aspiration in Chronic Obstructive Pulmonary Disease.
PMID- 29939763
TI - The neurobiology of adaptation to seasons: Relevance and correlations in bipolar
disorders.
AB - Bipolar disorders (BDs) are severe and common psychiatric disorders. BD
pathogenesis, clinical manifestations and relapses are associated with numerous
circadian rhythm abnormalities. In addition, infradian fluctuations of mood,
social activity, weight and sleep patterns are very frequent in BD. Disease
course with a seasonal pattern (SP) occurs in approximately 25% of depressive and
15% of manic episodes, which is coupled to a more severe disease symptomatology.
The pathophysiological mechanisms of seasonal effects in BD await clarification,
with likely important clinical consequences. This review aims at synthesizing
available data regarding the underlying pathophysiological mechanisms of
seasonality in BD patients, with implications for future research directions in
the study of seasonality in BD. Three factors are suggested to play significant
roles in BD with SP, namely the suprachiasmatic nuclei, as well as the
melatonergic and photoperiodism systems. It is proposed that BD with SP may be
considered as a complex disorder resulting from the interaction of clock gene
vulnerabilities and biological clock neuroplasticity, with environmental factors,
such as the response to light. Light seems to play a key role in BD with SP,
mainly due to two seasonal signaling pathways: a light to cortex serotonin
transporter pathway, as well as a pathway connecting light to melatonin
synthesis. This provides a theoretical framework for BD with SP, including for
future research and clinical management. The review proposes that future research
should explore markers of seasonality in BD, such as plasma melatonin, sleep-wake
rhythms (with actigraphy) and genetic or epigenetic variants within the melatonin
synthesis pathway. The role of light in driving BD with SP is an active area of
research. Seasonality may also be intimately linked to wider aspects of BD,
including via interactions with the gut microbiome, the gut-liver axis,
cholesterol regulation, aspects of metabolic syndrome, vitamin D, decreased
longevity, suicide risk and medication treatment targets. Further research on the
role of seasonality in BD is likely to clarify the etiology, course and treatment
of BD more widely.
PMID- 29939764
TI - The Effect of Cognitive Load and Task Complexity on Automation Bias in Electronic
Prescribing.
AB - OBJECTIVE: Determine the relationship between cognitive load (CL) and automation
bias (AB). BACKGROUND: Clinical decision support (CDS) for electronic prescribing
can improve safety but introduces the risk of AB, where reliance on CDS replaces
vigilance in information seeking and processing. We hypothesized high CL
generated by high task complexity would increase AB errors. METHOD: One hundred
twenty medical students prescribed medicines for clinical scenarios using a
simulated e-prescribing system in a randomized controlled experiment. Quality of
CDS (correct, incorrect, and no CDS) and task complexity (low and high) were
varied. CL, omission errors (failure to detect prescribing errors), and
commission errors (acceptance of false positive alerts) were measured. RESULTS:
Increasing complexity from low to high significantly increased CL, F(1, 118) =
71.6, p < .001. CDS reduced CL in high-complexity conditions compared to no CDS,
F(2, 117) = 4.72, p = .015. Participants who made omission errors in incorrect
and no CDS conditions exhibited lower CL compared to those who did not, F(1,
636.49) = 3.79, p = .023. CONCLUSION: Results challenge the notion that AB is
triggered by increasing task complexity and associated increases in CL. Omission
errors were associated with lower CL, suggesting errors may stem from an
insufficient allocation of cognitive resources. APPLICATION: This is the first
research to examine the relationship between CL and AB. Findings suggest
designers and users of CDS systems need to be aware of the risks of AB.
Interventions that increase user vigilance and engagement may be beneficial and
deserve further investigation.
PMID- 29939765
TI - Differences in the treatment and control of hypertension in urban and rural
residents of the northeastern region of the People's Republic of China: a cross
sectional study.
AB - BACKGROUND: Hypertension is a significant global public health problem and an
important risk factor for cardiovascular diseases. We aimed to determine
treatment and control rates of hypertension and to explore related risk factors
by urban and rural areas. METHODS: A cross-sectional survey of 14,956
participants (>= 15 years) was conducted in Jilin Province, China from July 2014
to December 2015 using questionnaire forms and physical measurements. RESULTS:
Total rates of hypertension treatment, control, and controlled blood pressure
among treated subjects were 31.7%, 8.8%, and 27.9% in the Jilin Province. Rates
of hypertension treatment, control, and controlled blood pressure among treated
subjects were 35.9%, 13.7%, and 38.3% in urban areas and 28.4%, 5.0%, and 17.5%
in rural areas, respectively. Higher treatment of hypertension was associated
with older age, female sex, other races (except Han), and higher body fat
percentage in both areas. Among urban residents, higher education was
additionally associated with higher treatment of hypertension; among rural
residents, a family history of coronary artery disease and unemployment were
associated with higher treatment of hypertension. Higher control of hypertension
was associated with unemployment, married status, higher education, healthy body
mass index, lower abdominal waist circumference, non-smoking status, and lower
visceral adiposity index in urban residents; higher control of hypertension was
associated with younger age in rural residents. CONCLUSION: Treatment and control
rates of hypertension in urban and rural areas were lower than the national
average; blood pressure control in patients taking antihypertensive drugs needs
further improvement.
PMID- 29939766
TI - Development and evaluation of fluorescent gold nanoparticles.
AB - OBJECTIVE: It is difficult to identify the gold nanoparticles (AuNPs)
intracellularly due to their non-fluorescent nature. Although gold can quench the
fluorescence of any fluorophore, hence it is also difficult to combine gold with
a fluorophore such as a semiconductor quantum dots (QDs). The aim of this study
was to prepare a single fluorescent stable AuNPs combined with QDs (QDs-Au-NPs)
which can be easily detected intracellularly. METHODS: QDs-Au-NPs were prepared
via a simple one-step process through controlling the spacing between them using
polyethylene glycol (PEG) as space linker in the form of PEGylated QDs.
Furthermore, the applicability of this system was evaluated after coating the
particles with somatostatin citrate, SST, to active target somatostatin receptors
(SSTRs), and identification of the internalized particles via confocal laser
scanning spectroscopy. RESULTS: The results showed that the produced Au shell has
a thickness of 2.0 +/- 0.2 nm and QDs-Au-NPs showed the same fluorescence
intensity compared to the unmodified QDs. Additionally, a stable monodisperse QDs
Au-NPs coated with SST were prepared after coating with 11-Mercaptoundecanoic
acid. Moreover, cellular uptake study in Human Caucasian breast adenocarcinoma
cell lines showed that QDs-Au-SST-NPs could be detected easily using the confocal
microscope. In addition, they showed a significant (p <= .05) internalization per
cell compared to untreated QDs-Au-NPs as detected by flow cytometry. CONCLUSION:
It could be concluded that the produced QDs-Au-NPs has a strong fluorescence
property like QDs which enable them to be easily detected after cells
internalization.
PMID- 29939767
TI - Redundant Automation Monitoring: Four Eyes Don't See More Than Two, if Everyone
Turns a Blind Eye.
AB - BACKGROUND: In safety-critical and highly automated environments, more than one
person typically monitors the system in order to increase reliability. OBJECTIVE:
We investigate whether the anticipated advantage of redundant automation
monitoring is lost due to social loafing and whether individual performance
feedback can mitigate this effect. METHOD: In two experiments, participants
worked on a multitasking paradigm in which one task was the monitoring and cross
checking of an automation. Participants worked either alone or with a team
partner on this task. The redundant group was further subdivided. One subgroup
was instructed that only team performance would be evaluated, whereas the other
subgroup expected to receive individual performance feedback after the
experiment. RESULTS: Compared to participants working alone, those who worked
collectively but did not expect individual feedback performed significantly less
cross-checks and found 25% fewer automation failures. Due to this social loafing
effect, even the combined team performance did not surpass the performance of
participants working alone. However, when participants expected individual
performance feedback, their monitoring behavior and failure detection performance
was similar to participants working alone and a team advantage became apparent.
CONCLUSION: Social loafing in redundant automation monitoring can negate the
expected gain, if individual performance feedback is not provided. APPLICATION:
These findings may motivate safety experts to evaluate whether their
implementation of human redundancy is vulnerable to social loafing effects.
PMID- 29939768
TI - Contrast in the circadian behaviors of an electrodermal activity and bioimpedance
spectroscopy.
AB - Probing the electrical response of the human body is minimally invasive and a
promising area of investigation for future health care. The electrical responses
of individuals may vary depending on daily physiological rhythms or environmental
changes, which may hamper their prediction for pathological status. In this
study, we observed circadian expressions via both alternating current (AC) and
direct current (DC) electrical responses of the human body using bioelectrical
impedance analysis (BIA) and electrodermal activity (EDA). In total, 14 healthy
adults (9 males and 5 females) participated and were hospitalized for 2 nights
with controlled caloric intake, sleep hours and residential conditions. The EDA
data showed a significant circadian rhythm, but the BIA data did not show
significant modulations during the measurement period. No difference was found
between circadian changes in male and female participants. The acrophase of the
EDA voltage response showed similar behavior with variations in the heart rate
variability, with a resistance minimum occurring at approximately 4 pm, implying
that the behavior of the EDA is probably affected by the sympathetic nerve
response. Moreover, the resistance of the EDA varied by up to 15% from its mean
value, which suggests that circadian variations cannot be neglected for the
correct diagnosis of pathological conditions. In contrast, the BIA method did not
show this circadian variation but showed independent results over the measurement
period. This difference in performance implies that the DC and AC responses of
the human body contain different electrophysiological information.
PMID- 29939769
TI - Endobronchial Lung Volume Reduction in Severe Emphysema. Time to Translate
Randomized Controlled Trial Results into Routine Clinical Practice?
PMID- 29939771
TI - Antihypertensive drug reduction for treated hypertensive patients during the
summer.
AB - Seasonal winter-summer variation in blood pressure (BP) has been reported, but
there are few reports on the reduction of antihypertensive medication during the
summer. We aimed to investigate the prevalence and details of drug reduction
during the summer among outpatients. Among 667 patients, 90 patients (13.5%) had
their medication reduced during the summer. The highest rate of drug reduction
was for diuretics (17.5%). The patients whose medications were reduced (Group R)
took a larger number of drugs and more frequently took diuretics compared with
the subjects whose medications were unchanged (N = 559; with no reduction or
increase in drugs, Group UC). Moreover, both the office BP and morning home BP of
the patients in Group R were significantly lower compared with those of the
patients in Group UC. These results suggest that doctors tend to reduce
antihypertensive drugs to avoid an excessive decrease in BP especially in
patients receiving combination therapy including diuretics.
PMID- 29939770
TI - Effect of strength training combined with antioxidant supplementation on muscular
performance.
AB - This was a placebo-controlled randomized study that aimed to investigate the
effects of strength training (ST) combined with antioxidant supplementation on
muscle performance and thickness. Forty-two women (age, 23.8 +/- 2.7 years; body
mass, 58.7 +/- 11.0 kg; height, 1.63 +/- 0.1 m) were allocated into 3 groups:
vitamins (n = 15), placebo (n = 12), or control (n = 15). The vitamins and
placebo groups underwent an ST program, twice a week, for 10 weeks. The vitamins
group was supplemented with vitamins C (1 g/day) and E (400 IU/day) during the ST
period. Before and after training, peak torque (PT) and total work (TW) were
measured on an isokinetic dynamometer, and quadriceps muscle thickness (MT) was
assessed by ultrasound. Mixed-factor ANOVA was used to analyze data and showed a
significant group * time interaction for PT and TW. Both the vitamins (37.2 +/-
5.4 to 40.3 +/- 5.6 mm) and placebo (39.7 +/- 5.2 to 42.5 +/- 5.6 mm) groups
increased MT after the intervention (P < 0.05) with no difference between them.
The vitamins (146.0 +/- 29.1 to 170.1 +/- 30.3 N.m) and placebo (158.9 +/- 22.4
to 182.7 +/- 23.2 N.m) groups increased PT after training (P < 0.05) and PT was
higher in the placebo compared with the control group (P = 0.01). The vitamins
(2068.3 +/- 401.2 to 2295.5 +/- 426.8 J) and placebo (2165.1 +/- 369.5 to 2480.8
+/- 241.3 J) groups increased TW after training (P < 0.05) and TW was higher in
the placebo compared with the control group (P = 0.01). Thus, chronic antioxidant
supplementation may attenuate peak torque and total work improvement in young
women after 10 weeks of ST.
PMID- 29939772
TI - Methods for investigating crash risk: Comparing case control with responsibility
analysis.
AB - OBJECTIVE: There are two primary methods for establishing relative risk: case
control studies where crash and matched control data are collected separately,
and responsibility analysis, which exploits a single existing crash database by
using non-responsible drivers as an "induced exposure" control group (which is
less expensive and therefore more feasible for examining the large number of
substances that can impact driving behavior). Though both approaches are
scientifically sound and methodologically valid, each approach has its own
inherent obstacles to overcome. In this effort, we examine in detail how
different criteria for the development of control cases influence the accuracy of
crash-risk estimates for drivers with positive BACs. METHODS: We applied
responsibility analysis to crash-involved drivers in a recent crash case-control
study, thereby providing two sets of control cases: those from responsibility
analysis and those from the case control study. RESULTS: Case control and
responsibility analysis crash risk curves did not differ significantly,
indicating that both systems generate valid estimates of the relative crash risk
of drivers on the road. CONCLUSIONS: The results suggest that when researchers
are faced with finance or time constraints that make case-control studies
infeasible, responsibility analysis should be considered a viable alternate
methodological approach.
PMID- 29939773
TI - How far have biological therapies come in regenerative sports medicine?
AB - INTRODUCTION: Regular engagement in sports produces many health benefits, but
also exposes to increased injury risk. The quality of medical care available is
crucial not only for sports trauma but also to avoid overuse syndromes and post
traumatic degenerative conditions. Areas covered: We provide background
information on some clinical needs in sport injuries and describe the main
families of biological products used in clinical practice. We also discuss
limitations of the current clinical experience. Expert opinion: Sport and
exercise impairment affects different segments of the population with different
needs. The exceptional demands of elite athletes and subsequent media coverage
have created hype around regenerative therapies. Statistical evidence, whether
weak (cell products) or moderate (PRPs), is not enough to drive medical decisions
because of the heterogeneity of the biological products available and their
application procedures. Moreover, the specific needs of the different segments of
the population along with the available clinical evidence for each
musculoskeletal condition should be considered in the decision-making process.
There is urgent need to develop regenerative protocols combined with post
intervention rehabilitation, and gather meaningful clinical data on the safety
and efficacy of these interventions in the different populations segments.
PMID- 29939774
TI - Retinal Pericytes: Characterization of Vascular Development-Dependent Induction
Time Points in an Inducible NG2 Reporter Mouse Model.
AB - : Purpose/aim of the study: In the retina, defects in pericytes (PCs)
function/loss are associated with various complications; however, the exact
pathological mechanisms are still not fully elucidated. Following the behavior of
retina-resident PCs during health and disease will reveal new insights for both
the understanding of pathological mechanisms and the development of new
regenerative therapies for the treatment of retinopathies. The main goal of this
study is to determine whether the NG2-reporter mouse (NG2CreERTM-eGFP) is a
suitable model to study the fate of retina-resident PCs. MATERIAL AND METHODS:
Vascular development-dependent reporter induction in retinal PCs was evaluated at
different time points [(a) > P21, (b) < P21, and (c) P1 to > P21)] and
additionally four different modes of application were tested. Reporter expression
was evaluated by enhanced green fluorescent protein (eGFP) immunofluorescence by
confocal microscopy and induction efficiency was calculated by analyzing NG2
expressing PCs in comparison to eGFP-labeled PCs in the three capillary layers.
RESULTS: eGFP-positive PCs were detected in the three retinal capillary layers at
all time points and administration routes tested. Multiple tamoxifen (TAM)
applications in adult (> P21) NG2CreERTM-eGFP mice resulted in 3.59% eGFP
positive PCs. 2.37% eGFP-labeled PCs were detected after single intraperitoneal
TAM injections at early postnatal days (P2/P5); however, just 1.61% PCs revealed
reporter expression upon activation via the lactating mother (P4-P7). The highest
number of eGFP-labeled PCs (7.09%) was detected following triple TAM
administrations (P10-P12). The number of reporter-positive PCs doubled using
homozygous animals. CONCLUSION: Despite low recombination efficiency in the used
PC-specific fate mapping mouse model, changes in NG2 promoter activity of PCs
during vascular development are indicated by single and multiple TAM inductions
at different developmental time points. Nevertheless, these findings need further
confirmation in up-coming studies by using homozygous NG2CreERTM-eGFP mice and
additionally by mating the NG2CreERTM with a different reporter mouse to increase
the low recombination efficiency.
PMID- 29939775
TI - Primary Descemet's Membrane Endothelial Keratoplasty for Fuchs Endothelial
Dystrophy versus Bullous Keratopathy: Histopathology and Clinical Results.
AB - PURPOSE: To investigate functional and anatomical results up to 12 months after
Descemet's membrane endothelial keratoplasty (DMEK) for Fuchs' endothelial
dystrophy (FED) versus bullous keratopathy (BK) in consideration of morphologic
characteristics on host's endothelium-Descemet's membranes (EDM). METHODS: In a
prospective consecutive case series, 119 eyes underwent a primary DMEK for FED or
BK. Intraoperatively obtained EDM were investigated immunohistologically.
Clinical and morphological parameters were compared between FED and BK. RESULTS:
Overall, the 12-months best-corrected visual acuity (BCVA) was 0.14 logMAR, and
0.10 logMAR in eyes without vision-limiting comorbidities; thereby no differences
were revealed between eyes with FED and BK up to 12 months postoperative (p =
0.186 and p = 0.095, respectively). Correspondingly, the mean central corneal
thickness (CCT) measured 520 vs. 529 um and the mean endothelial cell density
(ECD) was 1743 vs. 1457 cells/mm2 for FED and BK, 12 months postoperative.
Regarding CCT and ECD, no differences were observed between the groups (p = 0.181
and p = 0.112, respectively). The overall detachment rate was 40% (48/119).
Comparing FED and BK the detachment rates did not differ, which were 41% vs. 39%
and 43% vs. 35%, in pseudophakic eyes (p = 0.554 and p = 0.601, respectively).
Yet, the distribution of recurring graft detachments differed between FED and BK;
secondary re-detachments were more frequent in the FED group (7 cases). Regarding
histologic investigations, a lower ECD was found in specimens with BK, no
differences were revealed for EDM and anterior banded layer thicknesses.
Immunohistologically, differences in the distribution of fibronectin and
cytokeratin were observed. A rarification of matrix proteins was found in EDM
complexes with FED. CONCLUSIONS: DMEK produces similar results for FED and BK.
However, the postoperative course may differ with regard to the recurrence of
secondary graft detachments that may be associated by histopathologic
particularities.
PMID- 29939776
TI - Mutation Survey of Candidate Genes and Genotype-Phenotype Analysis in 20
Southeastern Chinese Patients with Axenfeld-Rieger Syndrome.
AB - : Purpose/aim of the study: To conduct a survey spectrum of the PITX2, FOXC1, and
PRDM5 genes to reveal genotype-phenotype correlations in a cohort of Southeastern
Chinese patients with Axenfeld-Rieger syndrome (ARS). MATERIALS AND METHODS: A
total of 20 probands with ARS were recruited in Southeast China. All patients
underwent full ocular and systemic examinations. Sanger sequencing was used to
analyze all coding regions of and regions adjacent to PITX2, FOXC1, and PRDM5 and
13 upstream regulatory elements of PITX2. Multiplex ligation-dependent probe
amplification was performed to detect gross insertions and deletions in PITX2 and
FOXC1. Quantitative polymerase chain reaction was used to detect copy number
variations in regulatory elements of PITX2. A bioinformatics analysis was
conducted to evaluate the pathogenicity of variants. RESULTS: Eleven mutations,
including eight novel mutations, were identified in PITX2. Seven of the mutations
were truncations. A genotype-phenotype correlation analysis showed that 81.8%
(9/11) of patients with mutations in PITX2 developed glaucoma before reaching 10
years old. The proportion of patients without detected mutations was only 33.3%
(3/9, P = 0.0399). In patient G1399, ultrasound biomicroscopy revealed that the
left eye exhibited a phenotype similar to aniridia with complete angle closure
and a remaining stub of iris tissue. CONCLUSION: This is the first genetic study
of a cohort of Southeastern Chinese patients with ARS. Eight novel mutations were
detected, expanding the mutation spectrum of PITX2. PITX2 may be a major
candidate gene for ARS in Southeastern Chinese patients. Truncations may be the
primary mutation type in PITX2. Glaucoma onset may be earlier in patients with
mutations in PITX2 than in those without mutations in PITX2 and FOXC1. A block of
the anterior chamber angle by the end of the iris might represent the main factor
influencing the development of glaucoma in ARS patients with an asymmetric
aniridia phenotype.
PMID- 29939777
TI - Immunohistochemical Expression of p16 in Melanocytic Lesions: An Updated Review
and Meta-analysis.
AB - CONTEXT: - Making an accurate diagnosis for melanocytic lesions has always been
challenging for pathologists, especially when dealing with difficult-to-diagnose
cases. Misdiagnosis of melanoma and melanocytic lesions in general has tremendous
medical-legal implications, often leading to unnecessary and excessive use of
adjunctive tests. Although molecular testing is of much interest and there is
great support for its development, currently, for most melanocytic lesions,
immunohistochemical studies remain the most practical method for assistance in
the routine diagnosis of melanocytic lesions for the average pathologist.
OBJECTIVES: - To review the practical use of p16 immunohistochemistry for
evaluating melanocytic lesions, particularly for differentiating benign from
malignant tumors, and to perform a meta-analysis of primary studies evaluating
p16 immunohistochemistry in melanocytic lesions. DATA SOURCES: - A PubMed
database search for literature reporting melanocytic lesions and p16
immunohistochemistry was performed. Essential information from each study (number
of samples, antibody used, collection dates, overall p16 immunohistochemistry
results, and general method of interpretation) was tabulated and analyzed.
Examples of representative cases showing p16 immunostaining pattern are also
illustrated. CONCLUSIONS: - Incorporation of p16 immunohistochemistry for the
diagnosis of melanocytic lesions is of limited use, especially for the purpose of
differentiating benign from malignant lesions. Evaluation of multiple studies
reveals a wide range of results. However, there appears to be some value for the
use of p16 in distinguishing nodal nevi from metastatic melanoma within nodes.
The method of interpretation (nuclear versus cytoplasmic staining) also appears
to give differing results, as studies considering only nuclear staining appeared
to show more consistent results from study to study.
PMID- 29939779
TI - Keeping Up With Testing Guidelines in Lung Cancer.
PMID- 29939778
TI - Management of a Hospital Transfusion Service During a Nationwide Blood Product
Shortage.
PMID- 29939780
TI - Liposuction-Induced Fat Embolism Syndrome: A Brief Review and Postmortem
Diagnostic Approach.
AB - Lipoplasty, or liposuction, the surgical process of removing excess fat, is an
elective procedure with rising frequency in the United States. Fat embolism
syndrome is a clinical diagnosis and is defined as fat in the circulation with an
identifiable clinical pattern of signs and symptoms (eg, hypoxemia, respiratory
insufficiency, neurologic impairment, and petechial rash) that occur in the
appropriate clinical context. Fat embolism syndrome following liposuction is a
life-threatening complication, although its incidence is low. Currently, there is
no specific therapy for fat embolism syndrome, so prevention, early detection,
and supportive therapy are critical. Many cases of fat embolism syndrome are
undiagnosed or misdiagnosed; however, postmortem examination can provide the
means for appropriate diagnosis. Therefore, a pathologist must keep a keen eye,
as microscopic fat emboli are difficult to appreciate with routine tissue
processing and staining.
PMID- 29939781
TI - The 16th Spring Seminar of the Korean Pathologists Association of North America.
PMID- 29939782
TI - Meningothelial-like Nodules of the Lung Show SSTR2a Immunohistochemical Staining.
PMID- 29939783
TI - The Effect of Hypoxia on Cardiovascular Disease: Friend or Foe?
AB - Savla, Jainy J., Benjamin D. Levine, and Hesham A. Sadek. The effect of hypoxia
on cardiovascular disease: Friend or foe? High Alt Med Biol. 19:124-130, 2018.
Over 140 million people reside at altitudes exceeding 2500 m across the world,
resulting in exposure to atmospheric (hypobaric) hypoxia. Whether this chronic
exposure is beneficial or detrimental to the cardiovascular system, however, is
uncertain. On one hand, multiple studies have suggested a protective effect of
living at moderate and high altitudes for cardiovascular risk factors and
cardiovascular disease (CVD) events. Conversely, residence at high altitude comes
at the tradeoff of developing diseases such as chronic mountain sickness and high
altitude pulmonary hypertension and worsens outcomes for diseases such as chronic
obstructive pulmonary disease. Interestingly, recently published data show a
potential role for severe hypoxia as a unique and unexpected therapy after
myocardial infarction. In this review, we will discuss the current literature
evaluating the effects of altitude exposure and the accompanying hypoxia on
health and the potential therapeutic applications of hypoxia on CVD.
PMID- 29939784
TI - Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by
activating the C/EBPbeta-related signaling pathway.
AB - Methamphetamine (Meth) is a widely abused psychoactive drug that primarily
damages the nervous system, notably causing dopaminergic neuronal apoptosis.
CCAAT-enhancer binding protein (C/EBPbeta) is a transcription factor and an
important regulator of cell apoptosis and autophagy. Insulin-like growth factor
binding protein (IGFBP5) is a proapoptotic factor that mediates Meth-induced
neuronal apoptosis, and Trib3 (tribbles pseudokinase 3) is an endoplasmic
reticulum (ER) stress-inducible gene involved in autophagic cell death through
the mammalian target of rapamycin (mTOR) signaling pathway. To test the
hypothesis that C/EBPbeta is involved in Meth-induced IGFBP5-mediated neuronal
apoptosis and Trib3-mediated neuronal autophagy, we measured the protein
expression of C/EBPbeta after Meth exposure and evaluated the effects of
silencing C/EBPbeta, IGFBP5, or Trib3 on Meth-induced apoptosis and autophagy in
neuronal cells and in the rat striatum after intrastriatal Meth injection. We
found that, at relatively high doses, Meth exposure increased C/EBPbeta protein
expression, which was accompanied by increased neuronal apoptosis and autophagy;
triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)
related mitochondrial apoptotic signaling pathway; and stimulated the Trib3
mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also
found that autophagy is an early response to Meth-induced stress upstream of
apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These
results suggest that Meth exposure induces C/EBPbeta expression, which plays an
essential role in the neuronal apoptosis and autophagy induced by relatively high
doses of Meth; however, relatively low concentrations of Meth did not change the
expression of C/EBPbeta in vitro. Further studies are needed to elucidate the
role of C/EBPbeta in low-dose Meth-induced neurotoxicity.-Xu, X., Huang, E., Luo,
B., Cai, D., Zhao, X., Luo, Q., Jin, Y., Chen, L., Wang, Q., Liu, C., Lin, Z.,
Xie, W.-B., Wang, H. Methamphetamine exposure triggers apoptosis and autophagy in
neuronal cells by activating the C/EBPbeta-related signaling pathway.
PMID- 29939785
TI - Oxytocin-like signaling in ants influences metabolic gene expression and
locomotor activity.
AB - Ants are emerging model systems to study cellular signaling because distinct
castes possess different physiologic phenotypes within the same colony. Here we
studied the functionality of inotocin signaling, an insect ortholog of mammalian
oxytocin (OT), which was recently discovered in ants. In Lasius ants, we
determined that specialization within the colony, seasonal factors, and
physiologic conditions down-regulated the expression of the OT-like signaling
system. Given this natural variation, we interrogated its function using RNAi
knockdowns. Next-generation RNA sequencing of OT-like precursor knock-down ants
highlighted its role in the regulation of genes involved in metabolism. Knock
down ants exhibited higher walking activity and increased self-grooming in the
brood chamber. We propose that OT-like signaling in ants is important for
regulating metabolic processes and locomotion.-Liutkeviciute, Z., Gil-Mansilla,
E., Eder, T., Casillas-Perez, B., Di Giglio, M. G., Muratspahic, E., Grebien, F.,
Rattei, T., Muttenthaler, M., Cremer, S., Gruber, C. W. Oxytocin-like signaling
in ants influences metabolic gene expression and locomotor activity.
PMID- 29939787
TI - Regenerating the kidney using human pluripotent stem cells and renal progenitors.
AB - INTRODUCTION: Chronic kidney disease is a major health-care problem worldwide and
its cost is becoming no longer affordable. Indeed, restoring damaged renal
structures or building a new kidney represents an ambitious and ideal alternative
to renal replacement therapy. Streams of research have explored the possible
application of pluripotent stem cells (SCs) (embryonic SCs and induced
pluripotent SCs) in different strategies aimed at regenerate functioning nephrons
and at understanding the mechanisms of kidney regeneration. Areas covered: In
this review, we will focus on the main potential applications of human
pluripotent SCs to kidney regeneration, including those leading to rebuilding new
kidneys or part of them (organoids, scaffolds, biological microdevices) as well
as those aimed at understanding the pathophysiological mechanisms of renal
disease and regenerative processes (modeling of kidney disease, genome editing).
Moreover, we will discuss the role of endogenous renal progenitors cells in order
to understand and promote kidney regeneration, as an attractive alternative to
pluripotent SCs. Expert opinion: Opportunities and pitfalls of all these
strategies will be underlined, finally leading to the conclusion that a deeper
knowledge of the biology of pluripotent SCs is mandatory, in order to allow us to
hypothesize their clinical application.
PMID- 29939786
TI - Lipin-1 regulates Bnip3-mediated mitophagy in glycolytic muscle.
AB - Autophagy of mitochondria (mitophagy) is essential for maintaining muscle mass
and healthy skeletal muscle. Patients with heritable phosphatidic acid
phosphatase lipin-1-null mutations present with severe rhabdomyolysis and muscle
atrophy in glycolytic muscle fibers, which are accompanied with mitochondrial
aggregates and reduced mitochondrial cytochrome c oxidase activity. However, the
underlying mechanisms leading to muscle atrophy as a result of lipin-1 deficiency
are still not clear. In this study, we found that lipin-1 deficiency in mice is
associated with a marked accumulation of abnormal mitochondria and autophagic
vacuoles in glycolytic muscle fibers. Our studies using lipin-1-deficient
myoblasts suggest that lipin-1 participates in B-cell leukemia (BCL)-2 adenovirus
E1B 19 kDa protein-interacting protein 3 (Bnip3)-regulated mitophagy by
interacting with microtubule-associated protein 1A/1B-light chain (LC)3, which is
an important step in the recruitment of mitochondria to nascent autophagosomes.
The requirement of lipin-1 for Bnip3-mediated mitophagy was further verified in
vivo in lipin-1-deficient green fluorescent protein-LC3 transgenic mice (lipin-1
/--GFP-LC3). Finally, we showed that lipin-1 deficiency in mice resulted in
defective mitochondrial adaptation to starvation-induced metabolic stress and
impaired contractile muscle force in glycolytic muscle fibers. In summary, our
study suggests that deregulated mitophagy arising from lipin-1 deficiency is
associated with impaired muscle function and may contribute to muscle
rhabdomyolysis in humans.-Alshudukhi, A. A., Zhu, J., Huang, D., Jama, A., Smith,
J. D., Wang, Q. J., Esser, K. A., Ren, H. Lipin-1 regulates Bnip3-mediated
mitophagy in glycolytic muscle.
PMID- 29939788
TI - Efficacy of Antimicrobial Agents for Food Contact Applications: Biological
Activity, Incorporation into Packaging, and Assessment Methods: A Review.
AB - Interest in the utilization of antimicrobial active packaging for food products
has increased in recent years. Antimicrobial active packaging involves the
incorporation of antimicrobial compounds into packaging materials, with the aim
of maintaining or extending food quality and shelf life. Plant extracts,
essential oils, organic acids, bacteriocins, inorganic substances, enzymes, and
proteins are used as antimicrobial agents in active packaging. Evaluation of the
antimicrobial activity of packaging materials using different methods has become
a critical issue for both food safety and the commercial utilization of such
packaging technology. This article reviews the different types of antimicrobial
agents used for active food packaging materials, the main incorporation
techniques, and the assessment methods used to examine the antimicrobial activity
of packaging materials, taking into account their safety as food contact
materials.
PMID- 29939789
TI - Effectiveness of Several Antimicrobials Used in a Postchill Decontamination Tank
against Salmonella and Campylobacter on Broiler Carcass Parts.
AB - New microbial performance standards for chicken parts necessitate postchill
antimicrobial interventions to make poultry parts safer for consumers. This
research was conducted to determine the effectiveness of antimicrobials (0.003%
chlorine; 0.07% acidified sodium chlorite [ASC], 0.07 or 0.1% peracetic acid
[PAA], and 0.35 or 0.60% cetylpyridinium chloride [CPC]) when used in a postchill
decontamination tank to reduce Salmonella and Campylobacter on broiler chicken
parts (including breasts, thighs, wings, and drumsticks) and to determine the
sensory attributes of the treated samples. Samples ( n = 90, 9 treatments * 5
samples * 2 replications) were inoculated with Salmonella Typhimurium (108
CFU/mL) and Campylobacter jejuni (108 CFU/mL). After a 30-min attachment time,
chicken parts were rinsed with various antimicrobials in a decontamination tank
for 23 s. Salmonella and Campylobacter reduction was determined by sampling parts
after the treatments were applied. Sensory evaluation of skin-on (drumettes) and
skin-off (breast meat) parts were conducted by untrained panelists by using an 8
point hedonic scale. CPC (0.35 or 0.60%), provided a reduction of 2.5 or 3.5 log
CFU/mL on Salmonella and a reduction of 4 or 5 log CFU/mL on Campylobacter,
respectively. Both concentrations of PAA (0.07 or 0.1%) provided a 1.5-log
reduction on Salmonella and Campylobacter. Chlorine at 0.003% and ASC at 0.07%
were the least effective antimicrobials, providing <1-log reduction for both
pathogens, which did not differ from the reduction provided by a water rinse
alone. Sensory attributes were unaffected in drumettes, and skinless breast
fillets received the most acceptable scores ( P <= 0.05) for texture, juiciness,
and overall acceptability when treated with 0.07% PAA and 0.35% CPC. Results from
this study indicated that using PAA and CPC in a postchill decontamination tank
are effective treatments for reducing Salmonella and Campylobacter on chicken
parts, with minimal effects on product quality.
PMID- 29939790
TI - Surface pH of Fresh Beef as a Parameter To Validate Effectiveness of Lactic Acid
Treatment against Escherichia coli O157:H7 and Salmonella.
AB - The U.S. beef industry must provide documentation to the U.S. Department of
Agriculture, Food Safety and Inspection Service (USDA-FSIS) that the
antimicrobial interventions implemented or any subsequent changes in the process
are effective under the actual conditions that apply in its operation. The main
objective of this study was to determine whether surface pH after application of
diluted lactic acid solution on surfaces of fresh meat can be used as a control
measure indicator for the reduction of E. coli O157:H7 and Salmonella. Samples
(240 each) of lean and adipose beef tissues were inoculated with cocktail
mixtures of Escherichia coli O157:H7 and Salmonella. Application parameters were
varied such that lean and adipose tissues were spray treated with either 2 or
4.5% lactic acid solution at either 38 or 60 degrees C for 1 to 10 s. Lean and
adipose tissues were collected before and after spray treatments for enumeration
of the pathogens. Based on the conditions of this study, there was no difference
between spray treatments at 38 or 60 degrees C, but 4.5% lactic acid solution
reduced pathogens more effectively ( P <= 0.05) than did 2% lactic acid solution.
Spray treatment with lactic acid solution for 1 to 10 s reduced surface pH values
of lean tissues (3 to 3.8) and adipose tissues (2.75 to 3.65). At surface pH
values of 3.0 and 2.75, lactic acid reduced E. coli O157:H7 on surfaces of lean
and adipose tissues by approximately 1.60 and 1.54 log CFU/cm2, respectively. At
surface pH values of 3.8 and 3.65, lactic acid reduced E. coli O157:H7 on lean
and adipose tissues by approximately 0.3 and 0.42 log CFU/cm2, respectively. The
surface pH values after lactic acid treatment and the reductions of both
pathogens showed a strong linear relationship; this indicates that a surface pH
of 3.1 would provide at least 1-log reduction of E. coli O157:H7 and Salmonella,
regardless of lactic acid application parameters. Therefore, surface pH after
spray treatment with lactic acid could be used to validate pathogen reduction.
PMID- 29939791
TI - Identification of Biological Hazards in Produce Consumed in Industrialized
Countries: A Review.
AB - Microbial contamination of fresh produce (fresh fruits and vegetables) poses
serious public health concerns worldwide. This study was conducted as a
comprehensive analysis of biological hazards in the global fresh produce chain.
Data about produce-related outbreaks and illness were collected from the annual
reports and databases of foodborne outbreak surveillance systems in different
regions and countries from 2010 to 2015. The global patterns of and regional
differences in documented outbreaks and cases were analyzed, and produce
commodities and pathogens of greatest concern were identified. Data on sporadic
illnesses were also collected through a comprehensive literature review of case
control studies. We found 988 produce-related outbreaks (with known agents) and
45,723 cases in all regions and countries. The numbers of produce-related
outbreaks per million person-years were approximately 0.76, 0.26, 0.25, 0.13,
0.12, and 0.05 in New Zealand, Australia, the United States, the European Union,
Canada, and Japan, respectively. The top three food categories and pathogens
contributing to produce-related outbreaks were vegetables and nonfruits (i.e.,
food other than fruits; 27.0%), unspecified vegetables (12.2%), and vegetable row
crops (11.7%) and norovirus (42.4%), Salmonella enterica (19.9%), and
Staphylococcus aureus (7.9%), respectively. Produce consumption was identified as
a protective factor, a risk factor, and either a protective or risk factor for
sporadic illnesses in 11, 5, and 5 studies, respectively, among 21 case-control
studies. Risks associated with produce consumption in the United States and the
European Union have been linked to various factors such as irrigation water,
cross-contamination, storage time and temperature abuse, infected food handlers,
and unprocessed contaminated ingredients. The results of the current study
indicate the complexity of produce products consumed across the globe and the
difficulty in tracing illnesses back to specific food ingredients.
PMID- 29939792
TI - A Comparative Study on the Effects of Quinic Acid and Shikimic Acid on Cellular
Functions of Staphylococcus aureus.
AB - Quinic acid (QA) and shikimic acid (SA), two kinds of natural organic acids, have
been reported to exhibit potent antibacterial activity against Staphylococcus
aureus. In this study, the effects of QA and SA on the cellular functions of S.
aureus were investigated by measuring the intracellular pH, intracellular and
extracellular ATP concentrations, succinate dehydrogenase activity, DNA content,
and interactions between SA and QA with S. aureus DNA. Studies of the cellular
functions demonstrated that QA could significantly decrease the intracellular pH,
whereas SA had no effect on intracellular pH. QA and SA reduced succinate
dehydrogenase activity and caused a significant decrease in intracellular ATP
concentration but no proportional increase in extracellular ATP. Moreover, QA and
SA both could remarkably reduce the DNA content of S. aureus and directly
interact with genomic DNA. The results suggested that the effects of QA and SA on
cellular functions were distinguishable, although the chemical structures of
these two compounds were similar. In conclusion, the results of the present
research suggested that SA and QA could be used as antibacterial agents in food
preservation.
PMID- 29939793
TI - Validation and Application of a Real-Time PCR Assay Based on the CRISPR Array for
Serotype-Specific Detection and Quantification of Enterohemorrhagic Escherichia
coli O157:H7 in Cattle Feces?.
AB - Several real-time quantitative PCR (qPCR) assays have been developed for
detection and quantification of Escherichia coli O157:H7 in complex matrices by
targeting genes for serogroup-specific O-antigen ( rfbEO157), H7 antigen, and one
or more major virulence factors (Shiga toxin and intimin). A major limitation of
such assays is that coamplification of H7 and virulence genes in a sample does
not signal association of those genes with the O157 serogroup. Clusters of
regularly interspaced short palindromic repeats (CRISPR) polymorphisms are highly
correlated with certain enterohemorrhagic E. coli (EHEC) serotypes, including
O157:H7, and the presence of genes for Shiga toxin ( stx1 and stx2) and intimin (
eae). Our objectives were to develop and validate a qPCR assay targeting the
CRISPR array for the detection and quantification of EHEC O157:H7 in cattle feces
and to evaluate the applicability of the assay for detection of and comparison
with a four-plex qPCR assay targeting rfbEO157, stx1, stx2, and eae genes and a
culture method. Detection limits of the CRISPRO157:H7 qPCR assay for cattle feces
spiked with pure cultures were 2.1 * 103 and 2.3 * 100 CFU/g before and after
enrichment, respectively. Detection of E. coli O157 in feedlot cattle fecal
samples ( n = 576) was compared among the CRISPRO157:H7 qPCR assay, culture
method, and four-plex qPCR assay. The CRISPRO157:H7 qPCR detected 42.2% of the
samples (243 of 576 samples) as positive for E. coli O157:H7, compared with 30.4%
(175 samples) by the culture method. Nearly all samples (97.2%; 560 samples) were
positive for rfbEO157 by the four-plex PCR, but 21.8% (122 of 560 samples) were
negative for the stx and/or eae genes, making it unlikely that EHEC O157:H7 was
present in these samples. Cohen's kappa statistic indicated a fair and poor
agreement beyond that due to chance between the CRISPR assay and the culture
method and four-plex assay, respectively. This novel qPCR assay can detect the
EHEC O157:H7 serotype in cattle feces by targeting CRISPR polymorphisms.
PMID- 29939794
TI - Metal Concentrations in Wild-Harvested Phaeophyta Seaweed from the Atlantic Ocean
(Canary Islands, Spain).
AB - Seaweeds are being consumed more often worldwide and are a source of essential
minerals, fiber, vitamins, amino acids, and various bioactive compounds that have
many beneficial effects on human health. However, marine pollution and the high
capacity of seaweed to absorb metals may mean this food can also be dangerous to
human health. The concentrations of some trace elements (B, Ba, Fe, Ni, Li, and
V) and toxic metals (Al, Cd, and Pb) were determined in various species of wild
seaweeds in the Phaeophyta group of brown algae from the Atlantic Ocean.
Inductively coupled plasma atomic emission spectrometry revealed high
concentrations of Al (256 mg/kg dry weight), Pb (3.92 mg/kg dry weight), and Cd
(0.20 mg/kg dry weight) in Padina pavonica. Pb contributed the most to the
tolerable daily intake (TDI) of toxic metals in these samples; 57.2 and 45.3% of
the TDI for Pb was found in 5 g of dehydrated P. pavonica and Halopteris
scoparia, respectively. This percent contribution is half of the recommended TDI
for this metal, which is 34.24 MUg/day; therefore, high consumption of these
species is discouraged. The maximum TDIs established by various institutions for
the other metals were not exceeded from the daily consumption of 5 g of the other
dehydrated seaweeds evaluated in this study.
PMID- 29939795
TI - Fluid reasoning and reading difficulties among children with ADHD.
AB - BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD)
commonly experience difficulties in reading and in fluid reasoning (Gf).
According to Cattell's Investment Theory (1987), Gf is a causal factor in the
development of crystallized knowledge (Gc) and academic skills; therefore, the co
occurrence of reading and Gf difficulties within ADHD may not be coincidental.
METHODS: In the present study with children with both ADHD and reading
difficulties (n = 187; 61% male; Mage = 9.2), we utilized mediation analyses to
test direct and indirect (through Gc, phonemic awareness, and rapid automatized
naming [RAN]) effects of Gf on four basic reading skills: untimed word
recognition, untimed phonemic decoding, word reading efficiency, and phonemic
decoding efficiency. RESULTS: The direct effect of Gf on all reading skills was
nonsignificant; however, significant indirect effects were observed.
Specifically, Gf exerted an effect indirectly onto all reading skills through a
serial and joint mechanism comprised of Gc and phonemic awareness (i.e., Gf -> Gc
-> phonemic awareness -> reading achievement). Gf also exerted an effect
indirectly onto untimed word recognition and phonemic decoding through phonemic
awareness (i.e., Gf -> phonemic awareness -> untimed word recognition/untimed
phonemic decoding). CONCLUSION: Results build upon Cattell's Investment Theory by
linking Gf with reading difficulties among children with ADHD, suggesting that
such difficulties may arise from weaknesses in Gf and insufficient investment of
Gf into reading through Gc and phonemic awareness.
PMID- 29939796
TI - Are there prototypical associations between time frames and aspectual values?
Evidence from Greek aphasia and healthy ageing.
AB - Time reference, which has been found to be selectively impaired in agrammatic
aphasia, is often interwoven with grammatical aspect. A recent study on Russian
aphasia found that time reference and aspect interact: Past reference was less
impaired when tested within a perfective aspect context (compared to when tested
within an imperfective aspect context), and reference to the non-past was less
impaired when tested within an imperfective aspect context (compared to when
tested within a perfective aspect context). To explain this pattern, the authors
argued that there are prototypical associations between time frames and aspectual
values. The present study explores the relationship between time reference and
aspect focusing on Greek aphasia and healthy ageing and using a sentence
completion task that crosses time reference and aspect. The findings do not
support prototypical matches between different time frames and aspectual values.
Building on relevant studies, we propose that patterns of performance of healthy
or language-impaired speakers on constrained tasks tapping different combinations
of time frames with aspectual values should reflect the relative frequency of
these combinations in a given language. The analysis of the results at the
individual level revealed a double dissociation, which indicates that a given
time frame-aspectual value combination may be relatively easy to process for some
persons with aphasia but demanding for some others.
PMID- 29939797
TI - Adaptation of commercial biomarker kits and proposal for 'drug development kits'
to support bioanalysis: call for action.
AB - There has been an increased use of commercial kits for biomarker measurement,
commensurate with the increased demand for biomarkers in drug development.
However, in most cases these kits do not meet the quality attributes for use in
regulated environment. The process for adaptation of these kits can be
frustrating, time consuming and resource intensive. In addition, a lack of
harmonized guidance for the validation of biomarker poses a significant challenge
in the adaptation of kits in a regulated environment. The purpose of this
perspective is to propose a tiered approach to commercial drug development kits
with clearly defined quality attributes and to demonstrate how these kits can be
adapted to perform analytical validation in a regulated environment.
PMID- 29939798
TI - Definitive profiling of plasma bile acids as potential biomarkers for human liver
diseases using UPLC-HRMS.
AB - AIM: Investigation of bile acids (BAs) as biomarkers for liver and kidney
diseases has gained momentum recently to fulfill the needs in drug development
and clinical practice, but a thorough and rapid profiling of BAs in human plasma
has been hindered by the large interindividual variability and lack of selective
methods. RESULTS: A selective and efficient UPLC-high resolution mass
spectrometry method was developed and fully validated for the definitive
profiling of 26 BAs in human plasma with a curve rage of 1-1000 ng/ml and a
runtime of 7.2 min. CONCLUSION: Four BA combinations with good sensitivity and
specificity show potential biomarker applications for liver injury and diseases.
PMID- 29939799
TI - Biomarker assay validation.
PMID- 29939800
TI - The effects of a laser-guided postural reeducation program on pain, neck active
range of motion, and functional improvement in a 75-year-old patient with
cervical dystonia.
AB - BACKGROUND AND PURPOSE: Limited research exists regarding physical therapy
management for patients with cervical dystonia (CD). The purpose of this case
report is to describe the clinical management of a patient with CD using manual
techniques, cervical traction, and laser-guided postural reeducation. CASE
DESCRIPTION: The patient was a 75-year-old female with CD, diagnosed 40 years
prior, with a 10-year history of botulinum neurotoxin injections. She reported a
1-year history of worsening neck pain and cervical range of motion loss which was
significantly affecting her ability to sleep and drive. The patient was seen for
12 visits over a 6-week period. OUTCOMES: Discharge scores indicated marked
improvements in active range of motion, neck disability index, and the CDIP-58
questionnaire. Improvement in motor control as measured during the SenMorCorTM
Laser Functional Error Assessment was demonstrated in the motions of "looking
right" (53%) and up (48%). DISCUSSION: This case report indicates that a physical
therapy program consisting of a daily laser-guided home program for head postural
reeducation in conjunction with classic physical therapy techniques may be an
option for patients with CD; however, further research is needed prior to
adoption of these techniques as standard of care for patients with CD.
PMID- 29939801
TI - The host response as a tool for infectious disease diagnosis and management.
AB - INTRODUCTION: A century of advances in infectious disease diagnosis and treatment
changed the face of medicine. However, challenges continue to develop including
multi-drug resistance, globalization that increases pandemic risks, and high
mortality from severe infections. These challenges can be mitigated through
improved diagnostics, and over the past decade, there has been a particular focus
on the host response. Since this article was originally published in 2015, there
have been significant developments in the field of host response diagnostics,
warranting this updated review. Areas Covered: This review begins by discussing
developments in single biomarkers and pauci-analyte biomarker panels. It then
delves into 'omics, an area where there has been truly exciting progress.
Specifically, progress has been made in sepsis diagnosis and prognosis;
differentiating viral, bacterial, and fungal pathogen classes; pre-symptomatic
diagnosis; and understanding disease-specific diagnostic challenges in
tuberculosis, Lyme disease, and Ebola. Expert Commentary: As 'omics have become
faster, more precise, and less expensive, the door has been opened for academic,
industry, and government efforts to develop host-based infectious disease
classifiers. While there are still obstacles to overcome, the chasm separating
these scientific advances from the patient's bedside is shrinking.
PMID- 29939802
TI - Update on trends in varicella mortality during the varicella vaccine era-United
States, 1990-2016.
AB - We reported previously that the annual average mortality rate in the United
States in 2008-2011 for varicella listed as the underlying cause declined 87%
compared with the prevaccine period (1990-1994). Here, we update the analysis
with five additional years of data. We used varicella death data from the 2012
2016 Mortality Multiple Cause-of Death records to calculate mortality rates
during 2012-2016 and trends since the prevaccine period and end of 1-dose
vaccination program (2005-2007). The annual average age-adjusted mortality rate
for varicella as the underlying cause was 0.03 per million population during 2012
2016, a 94% reduction from prevaccine years and a 47% reduction from 2005-2007.
Varicella deaths continue to decline due to the varicella vaccination program in
the United States.
PMID- 29939803
TI - Heavy menstrual bleeding: a global survey of health care practitioners'
perceptions.
AB - OBJECTIVES: This study sought to assess the perceptions of health care
practitioners (HCPs) regarding heavy menstrual bleeding (HMB). METHODS: We
developed an online survey for HCPs administered in 10 countries (Brazil, Canada,
China, France, Germany, Korea, Russia, Spain, UK and USA), in order to assess
their perceptions regarding HMB. RESULTS: We received 1032 responses. Most HCPs
considered more than 7 days of bleeding abnormal. There was a significant
difference in the definition of HMB between countries (p < .001). Most HCPs
measured menstrual blood loss by the number of sanitary pads or tampons needed,
followed by the impact on patients' daily activities. The majority of HMB
patients (61%) were diagnosed as having a non-structural disorder with no
causative identifiable coagulopathy. Patient acceptance and compliance were each
relevant for the treatment decisions of half of the HCPs. Treatment options for
idiopathic HMB featured mainly oral contraceptives and the levonorgestrel
releasing intrauterine system. Surgery was mentioned as a treatment option for
idiopathic HMB by 44% of HCPs. CONCLUSION: The definition of HMB and HCP
perceptions of HMB regarding diagnostic and therapeutic issues varied between
countries. Surgery was mentioned as a treatment for idiopathic HMB by nearly half
of HCPs. Clinician education is greatly needed to improve the management of women
with HMB.
PMID- 29939804
TI - Fertility management experiences of women with polycystic ovary syndrome in
Australia.
AB - BACKGROUND: Women with polycystic ovary syndrome (PCOS) are usually told that the
condition is associated with fertility difficulties. However, little is known
about their fertility management including contraceptive use, childbearing
desires, and pregnancy outcomes. AIM: To compare the fertility management
experiences and outcomes of Australian women with and without PCOS. METHOD: The
2013 Australian electoral roll was used to identify a random sample of 18- to 50
year-old women who were sent the Understanding Fertility Management in Australia
survey to be completed anonymously. Factors associated with fertility management
and outcomes were identified in multivariable analyses. RESULTS: Among the 1543
women who completed and returned the survey, 113 (7.3%) reported having PCOS.
Women with PCOS reported a similar rate of current contraceptive use as women
without PCOS (50.4% vs. 52.6%, p = .66). However, they were significantly younger
at first pregnancy (24.9 vs. 26.8 years, p = .015), more likely to have consulted
a health professional about fertility management (OR: 3.86, 95% CI: 2.50-5.96, p
< .001), and perceive that it would be difficult to conceive (OR: 2.31, 95% CI:
1.41-3.79, p = .001) than women without PCOS. There were no significant
differences in the number of desired children, unintended pregnancies, live
births, abortions or miscarriages between women with and without PCOS.
CONCLUSION: These findings indicate that women with PCOS need more nuanced
information about their fertility potential. While they may experience fertility
difficulties because of their condition, they should also be informed that they
can conceive spontaneously and need reliable contraception to avoid pregnancy
when it is not wanted.
PMID- 29939805
TI - "I enjoy the treadmill very much": Moving beyond traditional understandings of
self-efficacy in anti-obesity interventions.
AB - The last decade has seen increased focus on self-efficacy approaches in anti
obesity interventions. Self-efficacy approaches stemming from Bandura's social
cognitive theory involve enhancing the patient's self-efficacy to ensure behavior
change through exercise and dietary changes as well as weight-loss control.
Inspired by Barad's theory of agential realism, this study explores self-efficacy
by acknowledging that also non-human entities have agency. Drawing on one
adolescent's experiences of testing herself while running on a treadmill, we put
Barad's concept of "intra-acting" into play. Acknowledging the treadmill's agency
as well as the agency of the program itself enables us to see the becoming nature
of self-efficacy. As such, reading Bandura's concept of self-efficacy through
Barad helps us discover more clearly the contingent and fluid process of self
efficacy, a process of becoming that needs to account for both human and non
human actors. Regarding how adolescents' anti-obesity programs can be designed
and implemented to enhance self-efficacy, we argue that physiotherapists must
understand the intra-active processes involved in such programs.
PMID- 29939806
TI - Facilitating patient participation in physiotherapy: Symptom-talk during exercise
therapy from an Asian context.
AB - BACKGROUND AND PURPOSE: Patient participation is the cornerstone for effective
physiotherapy intervention. The aim was to analyze how patients and
physiotherapists negotiate symptoms during exercise therapy and describe
patients' participation during this process. METHODS: Nineteen consultations with
sixteen patients and six physiotherapists were video-recorded in two Hong Kong
outpatient settings. Conversation Analysis was used to uncover interactional
aspects of symptom-talk, focusing on turn-taking, sequence organization, and
vocabulary. RESULTS: Physiotherapists explored patients' symptoms only minimally
and their frequent use of closed-ended questions allowed limited opportunity for
participation. For patient-initiated symptom-talk, less than half elicited
actions from physiotherapists, whose minimal acknowledgments were often accepted.
Yet, some patients achieved a more substantial contribution through: (1) pausing
the exercise-in-progress; (2) gazing at the physiotherapist; (3) pointing at the
painful area; and (4) interrupting the physiotherapist, thereby challenging the
social order. While discussion about symptoms was often initiated by
physiotherapists, some patients participated actively by engaging in certain
communicative strategies. CONCLUSIONS: Patient participation can be improved by
physiotherapists offering a supportive environment (i.e., question design,
responding to patients' initiations, and promoting health literacy), and by
patients embracing action-engendering communicative strategies. The fine details
of interaction shed light onto the subtleties of symptom-talk initiated by
patients or physiotherapists in physiotherapy.
PMID- 29939807
TI - A potential role for protein O-fucosylation during pollen-pistil interactions.
AB - Putative protein O-fucosyltransferases (POFTs) represent a large family of
Glycosyl Transferase family 65 domain-containing proteins in land plants, with at
least 39 proposed members in the Arabidopsis thaliana genome alone. We recently
identified a member of this family, AtOFT1 (At3g05320), in which loss-of-function
mutants display impaired sexual reproduction that was linked to a defective male
gamete. Specifically, oft1 mutant pollen tubes are ineffective at penetrating the
stigma-style interface leading to a drastic reduction in seed set and a nearly
2000-fold reduction in pollen transmission. Our findings establish that AtOFT1
plays a critical role in pollen tube penetration through the stigma/style in
Arabidopsis and further suggest an important role for protein O-glycosylation
events that potentially influence pollen tube mechanical strength or the ability
to respond to positional guidance cues during the process of tube growth and
fertilization.
PMID- 29939808
TI - Implementation to Optimization: A Tailored, Data-Driven Approach to Improve
Provider Efficiency and Confidence in Use of the Electronic Medical Record.
AB - PURPOSE: Nine months after the implementation of a new electronic medical record
(EMR) system at a single institution, physicians (MDs), nurse practitioners
(NPs), and physician assistants (PAs) expressed frustration with its use. We
aimed to test if an individually tailored training approach reduced time spent
with the EMR and increased confidence. MATERIALS AND METHODS: Two hours of
training were conducted in a one-on-one manner with a trainer. Content was
individualized according to the following: provider survey, EMR utilization
profile, and shadowing in clinic. Surveys assessed confidence before training and
immediately after training. Changes in time spent in various EMR activities
before training and after training were compared. RESULTS: Three trainers
delivered one-on-one training to 133 MDs, 42 NPs, and 10 PAs who specialized in
medical oncology. Participants reported an increase in confidence across all
activities, and almost all providers (98%) who responded to our survey agreed
that the training enhanced their efficiency. A non-statistically significant
trend toward reduction in the overall time in the system was observed. Time in
system was reduced primarily in activities such as documentation and ordering of
laboratory tests, imaging, medications, and chemotherapy. CONCLUSION: A
personalized and data-driven training approach was highly regarded by providers.
EMR usage reports provided extensive data to identify and prioritize training
content and were valuable to measure the impact of training on provider time in
system. With the growth of EMR implementation and the reported relationship of
EMR use to burnout, continuous and personalized training after EMR implementation
is effective to reduce the time in system and increase confidence.
PMID- 29939809
TI - Hydrogen Peroxide Might Bleach Natural Dentin by Oxidizing Phosphoprotein.
AB - Recent studies suggested that bleaching agents may whiten teeth by oxidizing the
fluorescent materials, which are the proteins located in the organic-inorganic
interface. Therefore, we postulated that fluorescence of dentin came from dentin
phosphoprotein (DPP) and that bleaching agents might bleach dentin by oxidizing
DPP. Fifty-six specimens were randomly divided into 4 groups and exposed to
distilled water, hydrogen peroxide (HP), ethylenediamine tetraacetic acid
disodium salt (EDTA), and acetic acid for 24 h. After measuring the organic and
inorganic components, fluorescence, and color characteristics of dentin before
and after exposure, we found that when DPP was removed from dentin by EDTA,
fluorescent intensity declined proportionally with the reduction in Raman
relative intensity, and dentin was whitened considerably, with an Delta E value 6
times higher than that of the distilled water group. On the contrary, due to the
incapability of acetic acid to dissolve DPP during decalcification, fluorescent
intensity values and tooth color remained nearly unchanged after exposure to
acetic acid. Dentin exposed to neutral HP showed no obvious morphologic and
organic/inorganic component changes except for the destruction of DPP. Similarly,
dramatically decreased fluorescent intensity and lightened color were found in
the HP group. Moreover, DPP solution of the HP group exhibited decreased
ultraviolet absorbance, especially between 250 and 300 nm, which arose from
aromatic amino acids. The results indicated that DPP was responsible for the
fluorescent properties of dentin and that HP might bleach dentin by the
oxidization of aromatic amino acids in DPP. These findings are of great
significance in promoting our further understanding of the mechanism of tooth
bleaching and the fluorescent property of normal dentin.
PMID- 29939810
TI - Implementation of the comprehensive care for joint replacement model: A post
acute physical therapy case report.
AB - BACKGROUND: The Centers for Medicare and Medicaid services has specifically
targeted total joint replacements with a retrospective bundled payment program
called the Comprehensive Care for Joint Replacement (CJR) model to improve
collaboration between providers and decrease costs associated with the surgery
and subsequent rehabilitation. The purpose of this report is to describe the
physical therapy post-acute episode of care of a patient receiving services under
the CJR model and illustrate the impact of facility policy changes on physical
therapy service delivery, length of stay, cost of care, and patient outcomes in a
post-acute environment. CASE DESCRIPTION: The patient was a 78-year-old woman who
underwent an elective total knee arthroplasty (TKA). She had moderate mobility
impairments (total activities of daily living [ADL] score of 6) and was a high
fall risk as scored by the Physical Mobility Scale and Tinetti Mobility Test,
respectively. Physical therapy interventions focused on exercises to decrease
activity limitations and participation restrictions. OUTCOMES: The patient
demonstrated significant improvements in physical function after 22 total
physical therapy visits spanning her Skilled Nursing Facility and subsequent
outpatient treatment resulting in an intrafacility cost reduction of 52%.
Compared with the average number of visits and costs for post-acute care
following a TKA, this patient's care, under the CJR model, involved less cost and
required fewer visits. CONCLUSIONS: This case report supports some of the
proposed benefits of the CJR model for Medicare beneficiaries undergoing TKA.
PMID- 29939811
TI - Sport simulation as a form of implicit motor training in a geriatric athlete
after stroke: a case report.
AB - BACKGROUND AND PURPOSE: To describe the use of sport simulation activities as a
form of implicit motor learning training with a geriatric former athlete
following a stroke. CASE REPORT: An active 76-year-old former professional male
softball player presented to outpatient physical therapy with medical history of
right stroke with left hemiparesis 2 weeks following onset of symptoms of
impaired balance, coordination, gait, and motor planning. Initial physical
therapy included gait, balance, and coordination training. Additional sport
related balance and coordination activities were later added to the treatment
plan. OUTCOMES: After approximately 3 weeks of treatment, the patient was able to
return to work and had dramatically improved balance, coordination, and gait with
sport simulation activities. DISCUSSION: Implicit motor learning techniques were
incorporated through sport and job task simulation activities along with task
oriented neuromuscular reeducation. The patient demonstrated improvements with
gait, balance, gross motor function, and decreased fall risk.
PMID- 29939812
TI - Intelligent prescription system combined with a national pharmacloud for
geriatrics care.
AB - INTRODUCTION: The elderly are high risk for chronic diseases and multiple drug
use - two problems that make geriatric medication use more complex; as a result,
the possibility of duplicate prescriptions and drug interactions increase,
affecting patient safety. The objective of this study was to develop an
Intelligent Prescription System Combined with a National PharmaCloud for
Geriatrics Care (IPSPcG) that can reduce the occurrence of duplicate
prescriptions. METHODS: The system was implemented in a teaching hospital in
Taiwan. The IPSPcG consists of two major components: (1) the collection module
and (2) Intelligent Knowledge-base Module. Data on medication prescription
behaviors and medication-blocking rates were gathered from January 2015 to
December 2017. RESULTS: Overall, during the study period, the IPSPcG system
included 39,678 prescriptions. Antihypertensive medications were included at the
highest proportion (8962, 22.6%). The system changed physician's prescription
behavior (p < .001) and decreased potential duplicate prescription times (14%).
CONCLUSION: The results of this study show that integrating appropriate
recommendations from drug messages can reduce repeated drug prescriptions. Due to
the diversity of diseases, the diversity and accuracy of medical advice must
improve. The results of the 'Comprehensive Prescription Information' provided by
this system can serve as a reference for future research.
PMID- 29939813
TI - Radiosensitizer effect of usnic acid on Biomphalaria glabrata embryos.
AB - PURPOSE: Some phytochemicals have shown the potential of being radiomodifiers,
especially phenolic compounds, such as lichenic secondary metabolites. To
evaluate the phytochemical usnic acid as a radiomodifier, embryonic cells of
molluscs have been used due to their ease of collection, high sensitivity to
physical and chemical agents, well-known embryology and low cost for analysis.
MATERIALS AND METHODS: This study aimed to assess the radiosensitizing action of
usnic acid on Biomphalaria glabrata embryos. Samples were irradiated with 4 Gy of
gamma rays from a 60Co source (dose rate 2.906 Gy/h). An acute toxicity test was
performed using B. glabrata embryos in the blastula stage, in order to determine
the toxicity of usnic acid and to establish the lethal Concentration for 50%
(LC50). Subsequently, the radiomodifing capacity of usnic acid was estimated
using assays with B. glabrata embryos. RESULTS: Irradiation increased the number
of non-viable embryos compared to unirradiated controls. Additionally, it was
observed that embryos exposed to a non-toxic concentration of usnic acid (0.6
ug/mL) before irradiation showed a further enhancement in non-viable embryos when
compared with exposure to ionizing radiation alone. CONCLUSION: The results
presented here indicate that usnic acid makes cells more sensitive to the
damaging effects of radiation.
PMID- 29939814
TI - Tissue proteomics studies in the investigation of prostate cancer.
AB - INTRODUCTION: Prostate cancer (PCa) is one of the leading causes of death in the
male population worldwide. Various clinical samples such as urine, blood serum,
and prostatic fluid have been commonly used for the identification of PCa
associated molecular changes. Tissue, the site of oncogenesis, is increasingly
gaining more attention as a study material for studies aimed at the discovery of
biomarkers for predicting the disease outcome and therapeutic targets. Areas
covered: This review is the output of a systematic literature search on PubMed to
retrieve articles relevant to the proteomic analysis of tissues for the study of
PCa. Studies performed during the last 10 years using human tissues are
summarized. Expert commentary: Multiple proteomics studies were performed in the
past 10 years focusing on PCa initial diagnosis and staging. Even though some
reproducible findings have been reported, many studies lacked adequate validation
of findings and relied on relatively lower-resolution proteomics techniques
compared to the current state of the art. Incorporation of high-resolution
proteomics techniques, including investigations of protein post-translational
modifications (PTMs), is expected in the near future to complement other -omics
and enhance current efforts toward the molecular subtyping of PCa for patient
stratification.
PMID- 29939815
TI - Human mesenchymal stem cell therapy in the management of luminal and perianal
fistulizing Crohn's disease - review of pathomechanism and existing clinical
data.
AB - INTRODUCTION: Crohn's disease (CD) is a chronic, recurring, idiopathic disease
which is associated with imbalanced mucosal immune response, manifesting as a
chronic inflammation of any location throughout the gastrointestinal tract. The
purpose of currently available therapy is to suppress the heightened immune
response. However, these treatments have no direct influence on the healing
process of damaged tissues. The mesenchymal stem cell (MSC) therapy may represent
a new alternative solution in both luminal and fistulizing CD, as it is able to
inhibit the inflammation and promote the regeneration process at the same time.
Areas covered: Aim of this review is to summarize the existing clinical data
about the clinical impact of MSC therapy in luminal and perianal fistulizing CD.
Expert opinion: Clinical trials demonstrated that MSC transplantation has an
outstanding, durable efficacy with low fistula recurrence in biological therapy
refractory fistulizing CD; however, further clinical trials are required to
confirm its effectiveness in luminal CD. Unlike to biological therapy, MSCs are
able to promote the regeneration process of damaged tissues as well. This
additional benefit besides their sustained immunosuppressive effect with no
decrease of efficiency over time makes MSCs a new, highly potential therapeutic
approach in the management of inflammatory bowel disease.
PMID- 29939816
TI - HcTOK1 participates in the maintenance of K+ homeostasis in the ectomycorrhizal
fungus Hebeloma cylindrosporum, which is essential for the symbiotic K+ nutrition
of Pinus pinaster.
AB - Most land plants rely on root symbioses to complement or improve their mineral
nutrition. Recent researches have put forward that mycorrhizal fungi efficiently
absorb and transfer potassium (K+) from the soil to host plant roots, but the
molecular mechanisms involved are not completely elucidated yet. We have recently
revealed that K+ is likely released from the fungal Hartig net to the plant by
TOK channels in the ectomycorrhizal model Hebeloma cylindrosporum - Pinus
pinaster. H. cylindrosporum harbours three TOK members. Herein, we report that
one of them, HcTOK1, has similar features than the yeast ScTOK1. Moreover, we
propose a role for this channel in the transport of K+ from the medium to
ectomycorrhizal roots under K+ starvation.
PMID- 29939818
TI - Ser-Gln sites of SOG1 are rapidly hyperphosphorylated in response to DNA double
strand breaks.
AB - : The DNA damage response system (DDR) is crucial in addressing DNA double-strand
breaks (DSBs), which pose a severe threat to genomic integrity. The SOG1
transcription factor is a master regulator of the Arabidopsis thaliana DDR. We
previously showed that hyperphosphorylation of five Ser-Gln sites of SOG1 is the
molecular switch to activate the DDR. In this study, we determined that SOG1 is
hyperphosphorylated within 20 minutes following DSB-inducing treatment, followed
by activation of several SOG1 target genes. Using SOG1 phosphorylation mutants,
we demonstrated that although the hyperphosphorylation sites remain unchanged
over time, the amount of hyperphosphorylation gradually increases. These
observations suggest that rapid SOG1 hyperphosphorylation is limited by the
amount of active kinases. ABBREVIATIONS: SOG1, suppressor of gamma response; ATM,
Ataxia telangiectasia mutated; ATR, ATM and Rad3-related.
PMID- 29939817
TI - Interaction of sulfur with phytohormones and signaling molecules in conferring
abiotic stress tolerance to plants.
AB - Sulfur (S) is a macronutrient for the plant, which has an immense role in basic
plant processes and regulation of several metabolic pathways. It has also a major
role in providing protection against adverse conditions. Sulfur-containing amino
acids and metabolites maintain plant cell mechanisms to improve stress tolerance.
It interacts with several biomolecules such as phytohormones, polyamines, nitric
oxide (NO), and even with other plant nutrients, which can produce some
derivatives those are essential for abiotic stress tolerance. Different S
derivatives stimulate signaling cascades, for the upregulation of different
cellular messengers such as abscisic acid, Ca2+, and NO. Sulfur is also known to
interact with some essential plant nutrients by influencing their uptake and
transport, hence, confers nutrient homeostasis efficiencies. This review focuses
on how S is interacted with several signaling molecules like NO, glutathiones,
phytohormones, hydrogen sulfide, polyamines, etc. This is a concise summary aimed
at guiding the researchers to study S-related plant processes in the light of
abiotic stress tolerance.
PMID- 29939819
TI - Contraceptive use among migrant women with a history of induced abortion in
Finland.
AB - BACKGROUND: Women's contraceptive choices may change after an induced abortion,
due to contraceptive counselling or a behavioural change prompted by the
experience. The effect may vary between women; sociocultural background, for
example, may affect their subsequent reproductive choices. OBJECTIVE: We examined
whether women's current contraceptive use was differently associated with a
history of induced abortion among immigrant groups in Finland (Russian, Kurdish
and Somali) and the general Finnish population. METHODS: We analysed data from
two surveys, the Migrant Health and Wellbeing study and the Health 2011 study,
linked to the Finnish register of induced abortions. Propensity score weighted
logistic regression was used to analyse the data. RESULTS: The likelihood of
using contraceptives after an abortion varied depending on women's sociocultural
background. A history of induced abortion increased contraceptive use among all
groups, except Russian women, in whom there was no effect. The effect was
particularly strong for Kurdish women. CONCLUSION: Sociocultural background was
an important determinant of post-abortion contraceptive use. Some immigrants may
struggle to navigate the Finnish health care system due to language or literacy
issues. Attention should be paid to improving access to family planning among
these groups.
PMID- 29939821
TI - Pharmacological interventions for anxiety in Parkinson's disease sufferers.
AB - INTRODUCTION: Anxiety disorders are a common non-motor symptom of Parkinson's
disease (PD) with a reported prevalence ranging from 20% to 50%. Although anxiety
is associated with Parkinson's disease, anxiety disorders can begin before the
onset of motor symptoms, and have been linked to a possible abnormality of
dopaminergic, serotonergic, and adrenergic neurons that precedes motor
disturbance. Area covered: Several studies have reported the pharmacological
treatment of depression in PD, but none have been randomized clinical trials with
a primary outcome measure of anxiety. Two trials showed that pharmacological
intervention with tricyclic antidepressants or selective serotonin reuptake
inhibitors proved beneficial in treating anxiety in PD. However, the effect size
was modest. Anxiety is associated with off-periods and improved by L-Dopa,
especially in patients with high levels of anxiety. Expert opinion: Decreasing
off-periods is important for managing anxiety in patients with motor
fluctuations. Minor suggestive data indicate that tricyclic antidepressants and
selective serotonin reuptake inhibitors can be helpful with modest effect sizes,
but the former can cause additional side effects. Only one study has examined the
use of benzodiazepines to treat anxiety in PD, and benzodiazepines cannot be
recommended because they increase the risk of falling. Further clinical studies
for pharmacological intervention against anxiety are required.
PMID- 29939822
TI - Case series: effect of dermis-fat implants in different late onset socket
problems encountered in retinoblastoma patients.
AB - BACKGROUND: Cosmetic dissatisfaction, pain, and chronic discharge may present
months till years after enucleation in patients operated because of
retinoblastoma. If noninvasive treatment modalities are insufficient, socket
reconstruction can be considered. In this study, we discuss the results of dermis
fat exchange to treat these problems. METHOD: Four patients with late onset post
enucleation socket problems with a request for treatment were included in this
prospective study. Socket inspection was documented and pictures at baseline and
at a follow-up of at least 6 months were taken. To quantify the problem 'pain', a
VAS score at baseline and at follow up was used. For the problem 'cosmetic
dissatisfaction' standardized questionnaires were used. RESULTS: Two patients
were included because of cosmetic dissatisfaction; one was included with chronic
pain and one with chronic discharge. Reconstruction of the socket using
autologous dermis-fat insertion was done in all four. In one of them, severe
shrinking of the fat developed. This patient was treated with additional
injectable fillers. Both of them, ultimately, had satisfactory results.
Autologous fat transplantation also solved the problem of chronic discharge and
pain in the two other patients. CONCLUSION: Socket reconstruction by autologous
dermis-fat exchange may solve different post enucleation socket problems.
However, shrinking of the transplanted fat may occur and require additional
procedures.
PMID- 29939820
TI - Gag and env conserved element CE DNA vaccines elicit broad cytotoxic T cell
responses targeting subdominant epitopes of HIV and SIV Able to recognize virus
infected cells in macaques.
AB - HIV sequence diversity and the propensity of eliciting immunodominant responses
targeting inessential variable regions are hurdles in the development of an
effective AIDS vaccine. We developed a DNA vaccine comprising conserved elements
(CE) of SIV p27Gag and HIV-1 Env and found that priming vaccination with CE DNA
is critical to efficiently overcome the dominance imposed by Gag and Env variable
regions. Here, we show that DNA vaccinated macaques receiving the CE
prime/CE+full-length DNA co-delivery booster vaccine regimens developed broad,
potent and durable cytotoxic T cell responses targeting conserved protein
segments of SIV Gag and HIV Env. Gag CE-specific T cells showed robust anamnestic
responses upon infection with SIVmac239 which led to the identification of CE
specific cytotoxic lymphocytes able to recognize epitopes covering distinct CE on
the surface of SIV infected cells in vivo. Though not controlling infection
overall, we found an inverse correlation between Gag CE-specific CD8+ T cell
responses and peak viremia. The T cell responses induced by the HIV Env CE
immunogen were recalled in some animals upon SIV infection, leading to the
identification of two cross-reactive epitopes between HIV and SIV Env based in
sequence homology. These data demonstrate that a vaccine combining Gag and Env CE
DNA subverted the normal immunodominance patterns, eliciting immune responses
that included subdominant, highly conserved epitopes. These vaccine regimens
augment cytotoxic T cell responses to highly conserved epitopes in the viral
proteome and maximize response breadth. The vaccine-induced CE-specific T cells
were expanded upon SIV infection, indicating that the predicted CE epitopes
incorporated in the DNA vaccine are processed and exposed by infected cells in
their natural context within the viral proteome.
PMID- 29939823
TI - Abscisic acid-mediated phytochrome B signaling promotes primary root growth in
Arabidopsis.
AB - Plant photomorphogenic responses have been studied mostly using the shoots, the
core part of plant architecture that perceives light for photosynthesis and
influences the overall processes of growth and development. While the roots are
also known to respond to aboveground light through multiple routes of light
signal transduction, root photomorphogenesis has been less highlighted until
recently. A long-standing, critical question was how the underground roots are
capable of sensing aerial light and how the root-sensed light signals trigger
root photomorphogenesis. When the roots are directly exposed to light, reactive
oxygen species (ROS) are rapidly produced to promote primary root elongation,
which helps the roots to escape from the abnormal growth conditions. However,
severe or long-term exposure of the roots to light causes ROS burst, which impose
oxidative damages, leading to a reduction of root growth. We have recently found
that phytochrome B (phyB) promotes abscisic acid (ABA) biosynthesis in the shoots
and the shoot-derived ABA signals mediate ROS detoxification in the roots,
lessening the detrimental effects of light on root growth. On the basis of these
observations we propose that the phyB-mediated ABA signaling contributes to the
shoot-root synchronization that is essential for optimal growth and performance
in plants.
PMID- 29939824
TI - Vitamin A in Stargardt disease-an evidence-based update.
AB - BACKGROUND: High intake of vitamin A is suspected to be a risk factor for the
progression of Stargardt disease (STGD1) and many health authorities recommend
Stargardt patients not to use oral vitamin A supplements outside that provided
naturally in the food. The present study provides the first systematic review of
the current level of evidence regarding the role of supplementary vitamin A in
STGD1. MATERIALS AND METHODS: We conducted a systematic scientific literature
search in the Pubmed database on studies reporting on the effect of oral vitamin
A or serum retinol on visual function. RESULTS: In animal studies neither high
nor low serum retinol in an Abca4 knockout mouse model of Stargardt showed any
effect on electroretinography (ERG). In humans, significantly better visual
function was reported in a cross-sectional study of patients with a low dietary
intake of vitamin A, whereas a prospective study did not find any correlation
between vitamin A supplementation and visual acuity. A newly introduced vitamin A
substitute (C20-D(3)-vitamin A) has shown promising effects on ERG in a Stargardt
mouse model. CONCLUSIONS: There are few studies on the effect of vitamin A in
STGD1. The scarcity and inconclusiveness of evidence available impel further
research efforts to reach a more confident conclusion. Currently, recommendations
to avoid vitamin A dietary supplementation rely mainly on a theoretical
background. Animal studies on vitamin A substitute as a possible therapeutic
approach in preventing or slowing vision loss in STGD1 seems promising but
further clinical trials are needed to verify the results.
PMID- 29939825
TI - Defence cascade in Verticillium-infected grafted tomato.
AB - In tomato the Ve1-gene provides resistance to the vascular pathogen, Verticillium
dahliae, race 1; ve1 plants are susceptible. Reciprocal grafts of resistant and
susceptible tomato near-isolines were used to examine proteomic changes and, in
particular, the effect of the Ve1-gene on the defence/stress protein cascade
induced during Verticillium wilt. Based on label-free LC-MS, the results indicate
that this defence response is cell-specific, correlates with overall fungal
colonization and is mitigated by Ve1 function. The influence of the Ve1-gene in
resistant tissues, however, is not actually transferred to susceptible tissues in
the grafted plant.
PMID- 29939826
TI - Botulinum toxin-B injection into the lacrimal gland and posterior cricoarytenoid
muscle for the treatment of epiphora and abductor spasmodic dysphonia secondary
to Parkinson's disease.
AB - In ophthalmology, there have been few reports of botulinum toxin type-A (BTX-A)
injection into the lacrimal gland to treat epiphora. In ENT, adductor and
abductor (ABSD) spasmodic dysphonia are often treated with BTX-A injections into
the respective overacting vocal cord muscles. We describe a 53-year old male with
Parkinson's disease who did not respond to BTX-A injections to either the
lacrimal gland, for epiphora secondary to Parkinsonian-related blink
lagophthalmos, or posterior cricoarytenoid (PCA) muscles for ABSD. Subsequent BTX
type-B (BTX-B) injections into the lacrimal gland remarkably improved his
epiphora. BTX-B injections into the PCA muscle also greatly improved his
dysphonia. We describe the first reported case of (1) BTX-B injection into the
lacrimal gland for epiphora, (2) use of Botox in treating epiphora due to blink
lagophthalmos/reduced blink frequency secondary to Parkinson's disease, (3) BTX-B
use in treating ABSD, and (4) association between ABSD and Parkinson's disease.
PMID- 29939827
TI - The effects of a relaxation program featuring aquatic therapy and autogenic
training among people with cervical dystonia (a pilot study).
AB - Classic physical interventions for cervical dystonia (CD) have focused on
treating motor components or, on motor components and relaxation programs.
However, no CD treatment study has focused on a relaxation program alone. We
developed a pilot study to assess whether a therapy completely based on a
relaxation program could improve the physical and mental symptomatologies of
patients with CD. Fifteen persons were included in the experimental group, which
received individual sessions of aquatic (Watsu) therapy (WT) and autogenic
training (AT). In addition, 12 persons were included in passive control group. We
administered different questionnaires related to quality of life (SF-36), pain
(Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Visual Analog
Scale (VAS)) and mood (Beck Depression Inventory (BDI-II) and State-Trait Anxiety
Inventory (STAI)). A significant interaction was observed between treatment and
time with regard to the SF-36, VAS, and TWSTRS within the experimental group (p <
0.01). The BDI-II showed depression decrease as a simple effect (p < 0.05), and
the STAI did not change. No effects were found with regard to the control group.
In this exploratory study, we found that a therapy based on whole body relaxation
improved the symptoms of patients with CD. This knowledge enables a disease
management strategy that uses a holistic perspective and moves beyond the
dystonic focus.
PMID- 29939828
TI - Optimal threshold selection methods under tree or umbrella ordering.
AB - Receiver operating characteristic (ROC) curve is a popular tool for evaluating
diagnostic accuracy of biomarkers. In ROC framework, there exist several optimal
threshold selection methods for binary classification. For diseases with multi
classes, an important category of scenarios is tree or umbrella ordering in which
the marker measurement for one particular class is lower or higher than those for
the rest classes. Tree or umbrella ordering has important clinical applications,
especially in the molecular diagnostics of cancer subtypes. The ROC curve has
been extended to a typical ROC framework for tree or umbrella ordering (denoted
as TROC). In this paper, we investigate several methods for optimal threshold
selection under tree or umbrella ordering. Simulation studies are carried out to
explore the performance of these threshold selection methods. A real microarray
data set on lung cancer is analyzed using the proposed methods.
PMID- 29939830
TI - Neuromuscular anomalies following oral exposure to 3-nitro-1,2,4-triazol-5-one
(NTO) in a one-generation study with Japanese quail (Coturnix japonica).
AB - Substances used as explosives in munitions by the military often result in
environmental releases through manufacturing, testing, training, and combat
activities. The toxicity of 3-nitro-1,2,4-triazol-5-one (nitrotriazolone or NTO)
was evaluated following oral exposure in Japanese quail (Coturnix japonica) to
determine if environmental releases result in unacceptable risks to avian
populations. In an acute test at the limit dose (2000 mg/kg), one female was
ataxic, exhibited tremors, and showed signs of neurological toxicity
approximately 24 h after dosing. In a subsequent one-generation study, parental
generation (F0) birds were exposed orally to 1000, 500, 100, or 20mg/kg-day NTO
suspended in corn oil. After 5 consecutive days of dosing, 2-week-old birds
receiving 1000 mg/kg-day displayed ataxia, convulsions, backward arching of the
neck (opisthotonos), and alternated between prostrate inactivity and ataxic wing
activity. Birds in the 500 mg/kg-day group exhibited neuromuscular anomalies
after 17 days exposure. Ultimately, all of the 1000 mg/kg-day birds and all but
one of the 500 mg/kg-day birds met euthanasia criteria and were humanely
euthanized prior to behavioral and reproductive evaluation. As such, first
generation (F1) birds were exposed to 100 or 20 mg/kg-day NTO. Mild neuromuscular
anomalies occurred in 10% of F1 birds from the 100 mg/kg-day group, but not in
birds from 20 mg/kg-day or controls in either generation. Vacuolization of
cerebellum and/or the brainstem was observed on histopathologic examination in a
dose-dependent manner. Therefore, brain vacuoles and neuromuscular anomalies were
identified as critical endpoints in this study. A mean Benchmark Dose (BMD) for
brain vacuoles of 62 mg/kg-day was derived for male and female F0-generation
quail, which corresponded to a Benchmark Dose Low (BMDL10) of 35 mg/kg-day.
PMID- 29939829
TI - Fungal bioaerosols in biomethanization facilities.
AB - Biomethanization is a new technology used for green-waste valorization where
organic waste is biodegraded by microbial communities under anaerobic conditions.
The main product of this type of anaerobic digestion is a biogas used as an
energy source. Moving and handling organic waste may lead to the emission of high
concentrations of bioaerosols. High exposure levels are associated with adverse
health effects amongst green environment workers. Fungal spores are suspected to
play a role in many respiratory illnesses. There is a paucity of information
related to the detailed fungal diversity in biomethanization facilities. The aim
of this study was to provide an in-depth description of fungal bioaerosols in
biomethanization work environments using a next-generation sequencing approach
combined with real-time polymerase chain reaction (PCR). Two biomethanization
facilities treating different wastes were visited during the sampling campaign (n
= 16). Quantification of Penicillium/Aspergillus and Aspergillus fumigatus
revealed a greater exposure risk during summer for both facilities visited.
Concentrations of Penicillium and Aspergillus were similar in all work areas in
both biomethanization facilities. Taxonomy analyses showed that the type of waste
treated affects the fungal diversity of aerosols emitted. Although eight classes
were evenly distributed in all samples, Eurotiomycetes were more dominant in the
first facility and Agaricomycetes were dominant in the second one. A large
diversity profile was observed in bioaerosols from both facilities showing the
presence of pathogenic fungi. The following fungi detected are known allergens
and/or are opportunistic pathogens: Aspergillus, Malassezia, Emericella,
Fusarium, Acremonium, and Candida. Daily exposure to these fungi may put workers
at risk. The information from this study can be used as a reference for
minimizing occupational exposure in future biomethanization facilities.
Implications: Biomethanization is a new technology used for green-waste
valorization where organic waste is biodegraded by microbial communities.
Effective waste management is increasingly recognized as a strategic approach for
achieving newly created regulations concerning the disposal of organic residues;
therefore, an expansion of facilities is expected. Workers' exposure to diverse
fungal communities is certain, as fungi are ubiquitous and necessary in organic
matter decomposition. Monitoring this occupational exposure is important in order
to prevent workers' health problems.
PMID- 29939831
TI - Cupuacu (Theobroma grandiflorum) residue and its potential application in the
bioremediation of 17-Alpha-ethinylestradiol as a Pycnoporus sanguineus laccase
inducer.
AB - Bioremediation is a strategy to mitigate environmental impacts of hazardous
pollutants from anthropogenic sources. Natural byproducts, including
agroindustrial wastes (AW) can be used to induce enzyme biosynthesis, leading up
to enhancement of pollutants degradation process. Therefore, this study aimed to
evaluate the use of cupuacu, Theobroma grandiflorum AW as Pycnoporus sanguineus
Laccase (Lac) inducer in order to promote 17-alpha-ethinylestradiol (EE2)
bioremediation. The macro and micro-nutrients levels of cupuacu AWs were
evaluated in order to establish further correlations with enzymatic biosynthesis
induction. The fungus was cultivated for 7 days in temperature of 28 +/- 2
degrees C and agitation of 150 rpm. For bioremediation, Lac enzymatic extract was
added to EE2 solution (10 ug mL-1) and the percentage of removal was evaluated by
HPLC after 1-24 hr of reaction. At optimized conditions, the enzyme extract
production was remarkably enhanced by adding only 1% (w/v) of cupuacu AW. Lac
activity reached 1642 U mL-1 on the 6th day of culture, which was higher than
positive control (511 U mL-1). 86% of EE2 removal was reached after 4 hr, and
after 8 hr of reaction, 96.5% was removed. Analysis by direct infusion in MS-ESI
TOF exhibited intermediary compounds formed by radical hydroxilation.
PMID- 29939833
TI - Team mentored reflective practice in gerontological social work education.
AB - Attracting students to gerontological social work has long been difficult. A
possible strategy is to provide students with experiential learning opportunities
with older adults that provide them with support while reflecting on this work.
Our Team Mentored Reflective Practice model represents an effort to enhance
students' reflective practice skills in the context of a clinical research
project in which both instructors and students form a supportive team. Students
reported a number of benefits that included the development of meaningful
relationships with older clients, clinical skills that related to memory loss,
and the integration of research and practice. Students who were engaged in the
team mentored process of reflection evidenced changes in how they were thinking
about clients. These new understandings have the potential to impact the ways in
which students work with older adults.
PMID- 29939832
TI - Nitric oxide regulates lateral root formation through modulation of ACC oxidase
activity in sunflower seedlings under salt stress.
AB - Nitric oxide (NO) is established as a modulator of various developmental
processes in plants through its interaction with multiple enzymatic and non
enzymatic biomolecules. Lateral root (LR) induction and extension in sunflower
(Helianthus annuus L.) has been observed to be governed by a probable crosstalk
between NO and ethylene biosynthesizing enzyme-ACC oxidase. NaCl (120 mM) stress
not only lowers LR induction but also reduces their extension growth. Quenching
of endogenous NO by raising seedlings in presence of 40 uM hemoglobin in the
growth medium does not affect LR induction but lowers their extension growth.
NaCl stress and NO depletion have additive effects on the enhancement of ACC
oxidase activity, leading to enhanced ethylene biosynthesis. Role of NO has been
further confirmed by raising sunflower seedlings in the presence of 20-60 uM of
two NO donors, sodium nitroprusside (SNP) and diethylenetriamine NONOate (DETA).
LR extension growth was higher with DETA than SNP as NO donor at 40 uM. Iron
deficiency also promoted LR proliferation. It also significantly lowered ACC
oxidase activity in the seedling roots in response to salt stress. Based on the
present findings it is proposed that salt stress-mediated LR proliferation is
regulated by NO through its binding with ACC oxidase (an iron-containing enzyme).
This results in the formation of a stable ternary complex (ACC-ACC oxidase-NO)
which leads to the reduction in ethylene biosynthesis. Lesser availability of
ethylene consequently brings about enhanced LR formation.
PMID- 29939835
TI - Monoclonal Antibody MAb SZ-189 Against Recombinant Human CLEC-2 Protein.
PMID- 29939834
TI - Enhanced doxorubicin production by Streptomyces peucetius using a combination of
classical strain mutation and medium optimization.
AB - Doxorubicin (DXR), which is produced by Streptomyces peucetius, is an important
anthracycline-type antibiotic used for the treatment of various cancers. However,
due to the low DXR productivity of wild-type S. peucetius, it is difficult to
produce DXR by one-step fermentation. In this study, a DXR-resistance screening
method was developed to screen for DXR high-producing mutants. Then, S. peucetius
SIPI-11 was treated several times with UV and ARTP (atmospheric and room
temperature plasma) to induce mutations. Treated strains were screened by
spreading on a DXR-containing plate, isolating a mutant (S. peucetius 33-24) with
enhanced DXR yield (570 mg/L vs. 119 mg/L for the original strain). The
components of the fermentation medium, including the carbon and nitrogen sources,
were optimized to further enhance DXR yield (to 850 mg/L). The pH of the
fermentation medium and culture temperature were also optimized for effective DXR
production. Finally, DXR production by S. peucetius 33-24 was investigated in
flask culture and a fermenter. The yield of DXR was as high as 1100 mg/L in a 5-L
fermenter, which is the highest DXR productivity reported thus far, suggesting
that S. peucetius 33-24 has the potential to produce DXR by direct fermentation.
PMID- 29939836
TI - Thinking Cancer.
AB - Evolutionary theories are necessarily invoked for understanding cancer
development at the level of species, at the level of cells and tissues, and for
developing effective therapies. It is crucial to view cancer in a Darwinian
light, where the differential survival of individual cells is based on heritable
variations. In the process of this somatic evolution, multicellularity controls
are overridden by cancer cells, which become increasingly autonomous. Ecological
epigenetics also helps understand how rogue cells that have basically the same
DNA as their normal cell counterpart overcome the tissue homeostasis. As we
struggle to wrap our minds around the complexity of these phenomena, we apply
often times anthropomorphic terms, such as subversion, hijacking, or hacking, to
describe especially the most complex among them-the interaction of tumors with
the immune system. In this commentary we highlight examples of the
anthropomorphic thinking of cancer and try to put into context the relative
meaning of terms and the mechanisms that are oftentimes invoked to justify those
terms.
PMID- 29939837
TI - Differential pulmonary in vitro toxicity of two small-sized polyvinylpyrrolidone
coated silver nanoparticles.
AB - Silver nanoparticles (AgNP), with their important properties, are being used in a
range of sectors from industry to medicine, leading to increased human exposure.
Hence, their toxicity potential needs to be comprehensively evaluated. It was
postulated that within small-sized (<=20 nm) polyvinylpyrrolidone-coated silver
nanoparticles (PVP-AgNP), minor size differences may significantly induce
different toxicity profiles and involve varying cellular pathways. Therefore, the
aim of this study was to examine the influence of differing size AgNP with 10 nm
(AgNP10) and 20 nm (AgNP20) (up to 100 ug/ml), as well as to ionic silver as
AgNO3 for 24 and 48 h, using the human lung cell line A549. The effects on cell
viability, proliferation, apoptosis, DNA damage and cell cycle dynamics were
assessed. Results for both time periods showed that for low concentrations (<5
ug/ml), AgNP20 were more cytotoxic than AgNP10, however, at higher doses, AgNP10
exhibited higher toxicity. For concentrations >50 ug/ml, AgNP10 induced severe
DNA damage (comet class 3-4), cell cycle arrest at G2 phase and late-stage
apoptosis, while AgNP20 induced cell cycle arrest at S phase and an increase in
the percentage sub-G1, which did not recover after 48 h, and late-stage
apoptosis/necrosis. In longer-term exposures, the greater impairment in colony
formation due to AgNP exposure than to silver ion supports that nanotoxicity is
not exclusively due to the released ion. Data suggest that toxicity mediated by
small AgNP (<=20 nm) in lung cells is not only dependent on the level of particle
internalization, but also on AgNP size and concentration, which may involve
varying pathways as targets.
PMID- 29939838
TI - Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor
Receptor 2-Positive Breast Cancer: ASCO Clinical Practice Guideline Update.
AB - Purpose To update evidence-based guideline recommendations for practicing
oncologists and others on systemic therapy for patients with human epidermal
growth factor receptor 2 (HER2)-positive advanced breast cancer to 2018. Methods
An Expert Panel conducted a targeted systematic literature review (for both
systemic treatment and CNS metastases) and identified 622 articles. Outcomes of
interest included overall survival, progression-free survival, and adverse
events. Results Of the 622 publications identified and reviewed, no additional
evidence was identified that would warrant a change to the 2014 recommendations.
Recommendations HER2-targeted therapy is recommended for patients with HER2
positive advanced breast cancer, except for those with clinical congestive heart
failure or significantly compromised left ventricular ejection fraction, who
should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane
for first-line treatment and trastuzumab emtansine for second-line treatment are
recommended. In the third-line setting, clinicians should offer other HER2
targeted therapy combinations or trastuzumab emtansine (if not previously
administered) and may offer pertuzumab if the patient has not previously received
it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum
response, depending on toxicity and in the absence of progression. HER2-targeted
therapy can continue until time of progression or unacceptable toxicities. For
patients with HER2-positive and estrogen receptor-positive/progesterone receptor
positive breast cancer, clinicians may recommend either standard first-line
therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy
or endocrine therapy alone. Additional information is available at
www.asco.org/breast-cancer-guidelines .
PMID- 29939839
TI - Infiltrating the Blood-Brain Barrier in ALK-Positive Lung Cancer.
PMID- 29939840
TI - Recommendations on Disease Management for Patients With Advanced Human Epidermal
Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases: ASCO
Clinical Practice Guideline Update.
AB - Purpose To update the formal expert consensus-based guideline recommendations for
practicing oncologists and others on the management of brain metastases for
patients with human epidermal growth factor receptor 2-positive advanced breast
cancer to 2018. Methods An Expert Panel conducted a targeted systematic
literature review (for both systemic treatment and CNS metastases) and identified
622 articles. Outcomes of interest included overall survival, progression-free
survival, and adverse events. In 2014, the American Society of Clinical Oncology
(ASCO) convened a panel of medical oncology, radiation oncology, guideline
implementation, and advocacy experts, and conducted a systematic review of the
literature. When that failed to yield sufficiently strong quality evidence, the
Expert Panel undertook a formal expert consensus-based process to produce these
recommendations. ASCO used a modified Delphi process. The panel members drafted
recommendations, and a group of other experts joined them for two rounds of
formal ratings of the recommendations. Results Of the 622 publications identified
and reviewed, no additional evidence was identified that would warrant a change
to the 2014 recommendations. Recommendations Patients with brain metastases
should receive appropriate local therapy and systemic therapy, if indicated.
Local therapies include surgery, whole-brain radiotherapy, and stereotactic
radiosurgery. Treatments depend on factors such as patient prognosis, presence of
symptoms, resectability, number and size of metastases, prior therapy, and
whether metastases are diffuse. Other options include systemic therapy, best
supportive care, enrollment in a clinical trial, and/or palliative care.
Clinicians should not perform routine magnetic resonance imaging to screen for
brain metastases, but rather should have a low threshold for magnetic resonance
imaging of the brain because of the high incidence of brain metastases among
patients with HER2-positive advanced breast cancer. Additional information is
available at www.asco.org/breast-cancer-guidelines .
PMID- 29939841
TI - Methicillin-Resistant Staphylococcus aureus Parotitis Leading to Mortality in an
Adolescent Male.
AB - A case of toxic shock syndrome associated with methicillin-resistant
Staphylococcus aureus parotitis in a 13-year-old male is presented. He was
initially diagnosed with left-sided parotitis by his primary care physician, was
started on sulfamethoxazole/trimethoprim, and became severely ill the following
day. He was transported to the hospital after a syncopal episode at home and was
found to have altered mental status, hypotension, and hypoxia. He was transferred
to a larger care facility and died en route despite aggressive resuscitation. At
autopsy, he was found to have a severe left-sided parotitis, severe pulmonary
congestion, edema, and pneumonia, as well as bilateral lower limb hemorrhagic
lesions. Blood cultures from the time of admission and at autopsy grew
methicillin-resistant Staphylococcus aureus, which is rarely reported as the sole
cause of parotitis. In addition, although S. aureus bacteremia is not necessarily
a rare complication of a parotid gland infection, it is exceedingly rare in an
immunocompetent adolescent.
PMID- 29939842
TI - Sudden Death as a Sequel of Ruptured Giant Coronary Artery Aneurysm in Kawasaki
Disease.
AB - This article reports a case of Kawasaki disease (KD) and its rapid fatal course
in a 5-year-old boy, who 3 days before hospitalization demonstrated fever and
diffuse erythema in the face, neck, and torso, as well as swelling and pain below
the right earlobe. During the admission, he was diagnosed with mumps and
suspected scarlet fever. Abnormal laboratory findings included elevated values of
procalcitonin, C-reactive protein, and interleukin 6. Sudden death occurred 8
days after admission. Autopsy confirmed the cause of death to be pericardial
tamponade due to a ruptured, inflamed aneurysm of the left anterior descending
coronary artery. We believe that any typical clinical sign of KD whenever
associated with elevated indices of inflammation should set off suspicion of KD
and further permit cardiovascular examination. This would contribute to
distinguishing KD from other diseases with similar clinical signs in order to
accelerate appropriate treatment.
PMID- 29939844
TI - Should Asymptomatic Patients With Cervical Spinal Cord Compression and Spinal
Cord Signal Change Undergo Surgical Intervention?
PMID- 29939845
TI - Is there a Correlation Between Degree of Radiologic Lumbar Spinal Stenosis and
its Clinical Manifestation?
AB - STUDY DESIGN: This was an observational cross-sectional study. OBJECTIVE: The
purpose of this study was to evaluate whether the degree of stenosis on magnetic
resonance imaging (MRI) relates to the severity of clinical symptoms, disability,
or neurological deficit in patients with symptomatic central lumbar spinal
stenosis (LSS). SUMMARY OF BACKGROUND DATA: The relationship between radiologic
findings and the clinical manifestations of LSS remains unclear. MATERIALS AND
METHODS: A total of 84 patients (42 men, median age 70 y) with neurogenic
claudication and central degenerative LSS were included in the study. The MRI
parameters describing severity (anteroposterior diameter of dural sac, cross
sectional area of the dural sac, stenosis ratio, and Schizas qualitative
morphologic classification were evaluated at maximum stenotic level) and the
extent of stenosis (the number of central stenotic levels) were correlated to
symptoms (pain intensity, walking capacity), functional disability (measured in
terms of the Oswestry Disability Index), and neurological signs of LSS
(neurological status was evaluated and scored by Neurological Impairment Score in
LSS). RESULTS: A statistically significant correlation emerged only between the
Neurological Impairment Score in LSS and Schizas morphologic classification
(P=0.006). Pain intensity, walking capacity, and functional disability displayed
no correlation with the MRI parameters of LSS. CONCLUSIONS: LSS is a
clinicoradiologic syndrome with complex relationships between degree of
radiologic stenosis disclosed by MRI and clinical manifestations. Neurological
impairment in the lower extremities reflects the degree of morphologic LSS on
MRI. This study did not identify any association between the degree of stenosis
and functional disability, pain intensity, or walking capacity. LEVEL OF
EVIDENCE: Level II.
PMID- 29939843
TI - Motion Analysis in Lumbar Spinal Stenosis With Degenerative Spondylolisthesis: A
Feasibility Study of the 3DCT Technique Comparing Laminectomy Versus Bilateral
Laminotomy.
AB - STUDY DESIGN: This was a randomized radiologic biomechanical pilot study in vivo.
OBJECTIVE: The objectives of this study was to evaluate if 3-dimensional computed
tomography is a feasible tool in motion analyses of the lumbar spine and to study
if preservation of segmental midline structures offers less postoperative
instability compared with central decompression in patients with lumbar spinal
stenosis with degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: The
role of segmental instability after decompression is controversial. Validated
techniques for biomechanical evaluation of segmental motion in human live
subjects are lacking. METHODS: In total, 23 patients (mean age, 68 y) with
typical symptoms and magnetic resonance imaging findings of spinal stenosis with
degenerative spondylolisthesis (>3 mm) in 1 or 2 adjacent lumbar levels from L3
to L5 were included. They were randomized to either laminectomy (LE) or bilateral
laminotomy (LT) (preservation of the midline structures). Documentation of
segmental motion was made preoperatively and 6 months postoperatively with CT in
provoked flexion and extension. Analyses of movements were performed with
validated software. The accuracy for this method is 0.6 mm in translation and 1
degree in rotation. Patient-reported outcome measures were collected from the
Swespine register preoperatively and 2-year postoperatively. RESULTS: The mean
preoperative values for 3D rotation and translation were 6.2 degrees and 1.8 mm.
The mean increase in 3D rotation 6 months after surgery was 0.25 degrees after LT
and 0.7 degrees after LE (P=0.79) while the mean increase in 3D translation was
0.15 mm after LT and 1.1 mm after LE (P=0.42). Both surgeries demonstrated
significant improvement in patient-reported outcome measures 2 years
postoperatively. CONCLUSIONS: The 3D computed tomography technique proved to be a
feasible tool in the evaluation of segmental motion in this group of older
patients. There was negligible increase in segmental motion after decompressive
surgery. LE with removal of the midline structures did not create a greater
instability compared with when these structures were preserved.
PMID- 29939846
TI - Anticoagulation in a patient with antiphospholipid syndrome and a mechanical
heart valve: a case study.
AB - : A case report of a patient with antiphospholipid syndrome (APS) with positive
lupus anticoagulant and a mechanical mitral valve replacement (MVR) who presented
with a thrombosis and difficult-to-control INRs. Current literature on
anticoagulation options for patients who present with these conditions as well as
alternate laboratory assays are reviewed. APS can present a unique complexity and
challenge to appropriate anticoagulation on warfarin. Although there are emerging
data regarding the use of novel oral anticoagulants to treat this condition, they
do not justify their use in a patient with APS and an MVR because of a current
lack of evidence. CFX testing may be used to calibrate INRs when there is a
concern for false readings because of lupus anticoagulant interaction with INR
assays.
PMID- 29939847
TI - Maternal Body Mass Index and Use of Labor Neuraxial Analgesia: A Population-based
Retrospective Cohort Study.
AB - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
BACKGROUND:: Neuraxial labor analgesia may benefit obese women by optimizing
cardiorespiratory function and mitigating complications related to emergency
general anesthesia. We hypothesized that obese women have a higher rate of
neuraxial analgesia compared with nonobese parturients. METHODS: Using U.S.
natality data, our cohort comprised 17,220,680 deliveries, which accounts for
61.5% of 28 million births in the United States between 2009 and 2015. We
examined the relationships between body mass index class and neuraxial labor
analgesia, adjusting for sociodemographic, antenatal, pregnancy, and peripartum
factors. RESULTS: The study cohort comprised 17,220,680 women; 0.1% were
underweight, 12.7% were normal body mass index, 37% were overweight, and 28.3%,
13.5%, and 8.4% were obesity class I, II, and III, respectively. Rates of
neuraxial analgesia by body mass index class were as follows: underweight, 59.7%
(9,030/15,128); normal body mass index, 68.1% (1,487,117/2,182,797); overweight,
70.3% (4,476,685/6,368,656); obesity class I, 71.8% (3,503,321/4,881,938);
obesity class II, 73.4% (1,710,099/2,330,028); and obesity class III, 75.6%
(1,089,668/1,442,133). Compared to women with normal body mass index, the
likelihood of receiving neuraxial analgesia was slightly increased for overweight
women (adjusted relative risk, 1.02; 95% CI, 1.02 to 1.02), obese class I
(adjusted relative risk, 1.04; 95% CI, 1.04 to 1.04), obese class II (adjusted
relative risk, 1.05; 95% CI, 1.05 to 1.05), and obese class III (adjusted
relative risk, 1.06; 95% CI, 1.06 to 1.06). CONCLUSIONS: Our findings suggest
that the likelihood of receiving neuraxial analgesia is only marginally increased
for morbidly obese women compared to women with normal body mass index.
PMID- 29939848
TI - Bempedoic Acid (ETC-1002): ATP Citrate Lyase Inhibitor: Review of a First-in
Class Medication with Potential Benefit in Statin-Refractory Cases.
AB - Bempedoic acid (BA; ETC-1002) is a new agent that reduces cholesterol synthesis
through inhibition of adenosine triphosphate citrate lyase, an enzyme upstream
from 3-hydroxy-3-methylglutaryl-coenzyme A. In animal models, BA also influences
fatty acid synthesis, but in humans, its role is limited primarily to lowering
low-density lipoprotein cholesterol (LDL-C). In early clinical trials, BA was
well tolerated and without major side effects. Alone or in various combinations
with atorvastatin and/or ezetimibe, LDL-C lowering ranged from 17% to 64%. In
addition, BA lowers levels of non-high-density lipoprotein cholesterol, C
reactive protein, and apolipoprotein B. Statins are first-line agents for primary
and secondary prevention of cardiovascular disease. However, muscle-related side
effects and other problems such as elevated liver enzymes may limit their use. In
addition, LDL-C lowering beyond that provided by statin therapy alone may be
needed. BA may be useful in either of these scenarios, as it is relatively free
of muscle-related side effects and appears to enhance LDL-C lowering beyond that
achieved with statin monotherapy. Phase 3 trials and one outcomes study are
currently under way to better define this agent's potential clinical role.
PMID- 29939849
TI - Functional Mitral Regurgitation: An Interventional Cardiologist's Perspective.
AB - Functional mitral regurgitation (FMR) is common in patients with heart failure
and portends a poor prognosis. The etiology is secondary to nonischemic or
ischemic (postmyocardial infarction) adverse remodeling. Treatment includes
guideline-directed medical therapy, cardiac resynchronization therapy, and in
some cases, surgical repair or replacement. Transcatheter mitral valve (MV)
repair with the MitraClip device is approved in patients with degenerative MR and
is currently under investigation for use in FMR, as are several transcatheter MV
replacement devices. This review discusses the basis of FMR pathophysiology,
classification, and prognosis; provides an overview of current therapeutic
approaches; examines the available literature on the use of MitraClip in patients
with FMR; and provides insight into ongoing clinical trials and new
investigational devices for the treatment of FMR.
PMID- 29939850
TI - Emerging therapeutic options for management of anaemia in with patients with
chronic kidney disease.
PMID- 29939851
TI - Adverse events related to Trendelenburg position during laparoscopic surgery:
recommendations and review of the literature.
AB - PURPOSE OF REVIEW: Laparoscopy is routinely performed for the treatment and
management of gynaecologic disorders. During gynaecologic laparoscopy, the
patient is placed in the Trendelenburg position to optimize visualization and
access to the pelvis. The Trendelenburg position may result in complications in
many organ systems. RECENT FINDINGS: Trendelenburg positioning may cause rare,
potentially life-threatening complications of the respiratory and cardiovascular
systems. Case reports of visual field loss and cognitive aberrations following
Trendelenburg positioning have been published. Few intervention studies have been
performed evaluating attenuation of changes in intraocular pressure and
haemodynamics. SUMMARY: This review summarizes possible complications related to
the Trendelenburg position and current evidence regarding interventions to
minimize the risk of complications.
PMID- 29939852
TI - Hysteroscopic myomectomy: a comparison of techniques and review of current
evidence in the management of abnormal uterine bleeding.
AB - PURPOSE OF REVIEW: Submucosal uterine leiomyomas are a common benign pelvic tumor
that can cause abnormal uterine bleeding and may contribute to infertility and
miscarriage. Hysteroscopic myomectomy is the treatment of choice to alleviate
bleeding from these myomas and to normalize the uterine cavity. This review
discusses the techniques and recent evidence for hysteroscopic myomectomy and
examines the two primary surgical tools employed today: the bipolar resectoscope
and hysteroscopic mechanical morcellator. RECENT FINDINGS: Hysteroscopic
myomectomy has been a popular treatment for symptomatic submucosal fibroids for
decades; it is a minimally invasive, low-cost, low-risk procedure, and is
associated with high patient satisfaction. There have been rapid advances in the
surgical technology available for this procedure. Both the bipolar resectoscope
and the hysteroscopic mechanical morcellator are appropriate tools to remove
submucosal myomas. Although the hysteroscopic morcellators have been associated
with shortened operative time and a decreased learning curve, the data are
limited for their use on type 2 fibroids. The strength of the bipolar
resectoscope lies in its ability to resect deeper type 2 fibroids. SUMMARY: The
evidence suggests that no one technique should be used for all patients, but
rather a choice of technique should be taken on a case-by-case basis, depending
on the myoma number, size, type, and location. Gynecologists must become
knowledgeable about each of these techniques and their associated risks to safely
offer these surgeries to their patients.
PMID- 29939853
TI - Is oculofacial surgery complex ... or merely complicated?
AB - PURPOSE OF REVIEW: There is confusion in all of healthcare, including oculofacial
surgery, as to what is 'complex' and what is 'merely complicated'. Although in
common usage, these terms tend to be interchangeable, the distinction is more
than trivial. A different and somewhat unfamiliar toolset is needed to
successfully navigate complex problems. This review will explore a methodology
for the physician to understand what is complex in oculofacial surgery, the tools
needed to optimize performance in a complex healthcare system and successfully
manage patients with complex diseases. RECENT FINDINGS: A specific understanding
of complexity science in oculofacial surgery is only in its nascent beginnings at
this point. Nevertheless, recent advances in closely related fields can provide
concrete applications. The practice of oculofacial surgery is optimized within a
healthcare network of supporting professionals. Moreover, a newer understanding
of the 'complex' nature of disease common to oculofacial surgery, such as
neoplasia and inflammation, will direct the physician to recognize the most
appropriate therapies. SUMMARY: Oculofacial surgery, like all of medicine, is a
fluid mixture of problems that are complex and those that are merely complicated.
As a different toolset is needed to deal with each, physicians need to recognize
these differences and acquire those tools.
PMID- 29939855
TI - Skin Ceramide Profile in Children With Atopic Dermatitis.
AB - BACKGROUND: Atopic dermatitis (AD) is a common disease, which involves a
disruption of the skin barrier function. Skin ceramide (CER) composition, which
plays crucial roles in maintaining the barrier function of the stratum corneum,
is changed in patients with AD. OBJECTIVE: The aim of this study was to identify
and quantify skin CER subclasses in association with disease severity in
pediatric patients with AD. METHODS: Two hundred thirteen patients were entered
into the observational study. We compared their CER profiles using normal-phase
high-performance liquid chromatography coupled with dynamic multiple reaction
monitoring mass spectrometry. RESULTS: In total, 12 subclasses of CERs were
identified. We found that 2 subclasses, that is, CER[AS] and CER[NS], were
elevated (P = 0.007 and 0.012, respectively) and correlated with Severity Scoring
of Atopic Dermatitis (P = 0.004 and 0.004, respectively). CONCLUSIONS: Skin CER
abundances are changed in children with AD compared with control subjects.
PMID- 29939856
TI - Why Seek a Doctorate-Prepared Nurse to Join Your Team?
AB - Increasing numbers of doctoral-prepared nurses are joining interprofessional
health care teams. Interestingly, the evolving doctoral programs for nurse
leaders can be confusing to other health care professionals. Advanced education
for nursing leaders is driven by a growing need for cost-effective implementation
of evidence-based practices. Professional nursing organizations and nursing
education programs have redefined education to respond to the call for
knowledgeable experts to lead evidence-based quality improvements. As
interprofessional health care management teams face the daunting task of
selecting team members, an understanding of the differences in nursing doctoral
programs is needed. A doctor of nursing practice degree-prepared nurse can
strengthen the health care team by providing a skill set that includes not only
the ability to translate evidence into best practice, but also the ability to
communicate effectively with all members of the interprofessional team.
PMID- 29939854
TI - Chemokine Signaling in Allergic Contact Dermatitis: Toward Targeted Therapies.
AB - Allergic contact dermatitis (ACD) is a common skin disease that results in
significant cost and morbidity. Despite its high prevalence, therapeutic options
are limited. Allergic contact dermatitis is regulated primarily by T cells within
the adaptive immune system, but also by natural killer and innate lymphoid cells
within the innate immune system. The chemokine receptor system, consisting of
chemokine peptides and chemokine G protein-coupled receptors, is a critical
regulator of inflammatory processes such as ACD. Specific chemokine signaling
pathways are selectively up-regulated in ACD, most prominently CXCR3 and its
endogenous chemokines CXCL9, CXCL10, and CXCL11. Recent research demonstrates
that these 3 chemokines are not redundant and indeed activate distinct
intracellular signaling profiles such as those activated by heterotrimeric G
proteins and beta-arrestin adapter proteins. Such differential signaling provides
an attractive therapeutic target for novel therapies for ACD and other
inflammatory diseases.
PMID- 29939857
TI - The regularity of orthosis use and the reasons for disuse in stroke patients.
AB - This is a Retrospective descriptive study. Orthoses and walking aids are used
frequently in stroke rehabilitation to facilitate ambulation. The aim was to
describe the regularity of orthosis use and the reasons for disuse in stroke
after discharge from inpatient rehabilitation. The study included 64 (43 men, 21
women) subacute stroke patients who had been discharged from our clinic in the
last 6 months. Demographic and clinical findings, proposed orthoses and walking
aids, frequency of usage for the proposed orthoses, reasons for disuse, and the
ambulation levels were recorded. A total of 54 (84.4%) patients had an ankle-foot
orthosis and 10 (15.6%) patients had a knee-ankle-foot orthosis. The orthosis
frequency of use was every day in 38 (59.4%) patients and one to seven times a
week in seven (10.9%) patients, whereas 19 (29.7%) did not use them. The reasons
for orthosis disuse were finding them unnecessary in seven (27%) patients, usage
difficulties in six (23%) patients, pressure sensation in five (19.2%) patients,
the belief that they did not make life easier in five (19.2%) patients, lack of a
suitable environment in one (3.8%) patient, orthosis wear in one (3.8%) patient,
and systemic disease in one (3.8%) patient. Age, sex, residence, the disease
duration, and recommended orthosis duration (how long the prescribed orthosis was
used), recommended orthosis, range of motion limitation in the lower extremities,
presence of spasticity, type of orthosis, and the ambulation level were not
statistically significantly associated with the frequency of orthosis use
(P>0.05). The only significant clinical factor for the frequency of orthosis use
was the lower extremity Brunnstrom neurophysiological recovery stage (P<0.008).
Orthosis use had been discontinued by 29% of the patients. The most common
reasons reported for discontinuing orthosis use were that the patients found it
unnecessary, usage difficulty, pressure sensation, not making life easier, lack
of a suitable environment, and orthosis wear. The only significant clinical
factor for the frequency of orthosis use was the lower extremity Brunnstrom
neurophysiological recovery stage.
PMID- 29939858
TI - Paroxysmal Sympathetic Hyperactivity and Clinical Considerations for Patients
with Acquired Brain Injuries: A Narrative Review.
AB - The term "storming" has often been used colloquially to characterize brain
injured patients who showed signs and symptoms of elevated heart rate, blood
pressure, respiratory rate, temperature, and motor posturing. Recently, the term
paroxysmal sympathetic hyperactivity (PSH) has been used as the unifying term to
describe these acute episodes of elevated sympathetic hyperactivity. Various
pharmaceutical and management options are available, but no single drug or
protocol has been deemed superior to the others. Data on prognosis and recovery
in relation to PSH are limited, but point toward poorer functional outcome and
increased mortality. Overall, the phenomenon of PSH requires further research to
aid rehabilitative efforts so that patients can effectively participate in
therapy. A review of the literature has revealed sparse information on the
management of sympathetic storming within rehabilitation facilities. This
narrative review seeks to provide an up-to-date synopsis and recommendations on
the management of rehabilitation inpatients with PSH.
PMID- 29939859
TI - Management of patients with metastatic teratoma with malignant somatic
transformation.
AB - PURPOSE OF REVIEW: The purpose of this review is to examine the historical
context alongside contemporary studies in order to provide the most current
recommendations for the management of patients with metastatic teratoma with
malignant somatic transformation (MST). RECENT FINDINGS: The main themes in the
recent literature covered herein include prognostic features, the management of
early-stage disease, recommended chemotherapeutic and surgical strategies as well
as recognized patterns of late relapse. SUMMARY: Recent literature, combined with
a significant contribution from historical studies, suggests that while MST is
uncommon, its aggressive nature coupled with its resistance with traditional germ
cell tumor chemotherapies makes it very difficult to manage. The key message is
that surgery is recommended in all resectable MST from primary retroperitoneal
lymph node dissection for clinical stage I, to radical removal of disease after
chemotherapy and when chemotherapy fails. In advanced cases with documented
spread of the transformed histologic subtype, systemic therapies targeted to the
identified tumor type should be considered.
PMID- 29939860
TI - Medical treatment of urinary stones.
AB - PURPOSE OF REVIEW: To identify the latest progression on medical treatment of
urinary stones. RECENT FINDINGS: Nonsteroidal anti-inflammatory drugs should be
the preferred analgesic option for patients presenting to the emergency
department with renal colic. A-blockers could be of patient benefit when used for
distal ureteral stones more than 5 mm in size. However, the quality of the
randomized controlled studies on medical expulsive therapy (MET) is still low
based on the Consolidated Standards for Reporting Trials (CONSORT) criteria. MET
should be used with caution in children and pregnant women. In patients with
renal stones, the evaluation of the comorbidities of developing chronic Kidney
Disease (CKD) or End Stage Renal Disease (ESRD) is mandatory. It is highly
recommended to follow the European Association of Urology Urolithiasis Guidelines
Panel Diagnostic and Therapeutic algorithms to prevent stone recurrence. SUMMARY:
Medical treatment of urinary stone disease should be supported by well designed
higher level of evidence clinical research.
PMID- 29939861
TI - Cancer incidence in Mozambique in 2015-2016: data from the Maputo Central
Hospital Cancer Registry.
AB - There is scarce information on cancer incidence in Mozambique. We aimed to
describe cancer incidence data from the Cancer Registry of the Maputo Central
Hospital (MCH) in 2015-2016, for Maputo City dwellers, and to compare the
incidence rates with those observed in 1956-1961. Cancers with incidence data in
2015-2016 were identified by the Cancer Registry of the MCH. Crude and age
standardized incident rates (ASIR, per 100 000) - direct method, world standard
population - were computed for Maputo City, under the assumption that most cancer
cases among this population were identified at the MCH. A total of 1707 incident
cases in Maputo City dwellers were registered (76.6% confirmed histologically).
Prostate cancer, Kaposi sarcoma, and liver cancer were the most frequent in men
(ASIR: 24.5, 19.8, and 13.3, respectively). Cervical and breast cancers, and
Kaposi sarcoma were the most common among women (ASIR: 32.4, 11.8, and 9.5,
respectively). Compared with the data from 1956 to 1961, the most pronounced
declines in ASIR were for bladder and liver cancers, in both sexes, and increases
were greater for prostate cancer among men (172.2%) and breast cancer (237.1%)
among women. Our study highlights the high frequency of infection-related cancers
in Maputo, but also of those related to the ongoing demographic and socioeconomic
transition.
PMID- 29939862
TI - Do Personality Factors Assessed Before Cochlear Implantation Predict Hearing
Related Quality Of Life After Cochlear Implantation in Postlingually Deafened
Adults?
AB - BACKGROUND: Studies have shown that cochlear implants improve deaf patients'
hearing-related quality of life (hrQoL), but the degree of improvement varies
considerably between patients. This study investigated whether personality
factors contribute to hrQoL outcome after cochlear implantation. METHOD: Fifty
adult patients with postlingual hearing loss who received a unilateral cochlear
implant were administered the Neuroticism-Extraversion-Openness Five-Factor
Inventory (NEO-FFI; a personality inventory) and the Nijmegen Cochlear Implant
Questionnaire (NCIQ; a hrQoL questionnaire). The NEO-FFI was administered only
before implantation; the NCIQ was administered before implantation and 12 months
after implant activation. A linear regression analysis was computed to detect
whether NCIQ scores at 12 months were predicted by the NEO-FFI personality
factors (i.e., Extraversion, Neuroticism, Openness to Experience, Agreeableness,
and Conscientiousness) assessed before implantation. RESULTS: HrQoL scores had
significantly improved 12 months after cochlear implantation in all subdomains of
the NCIQ. Of the five personality factors, solely Neuroticism was negatively
associated to the NCIQ subdomain self-esteem (beta = -0.34; p = 0.013) at 12
months after cochlear implantation. CONCLUSIONS: While significant improvement of
hrQoL was seen 12 months after implant activation, this improvement was barely
predicted by the Big-Five personality traits measured before implantation. Only
Neuroticism was found to moderately influence postimplantation hrQoL in our
patients, in the way that higher degrees of Neuroticism tend to go along with
lower degrees of self-esteem (as conceptualized by the NCIQ). The failure to
detect personality effects on hrQoL could partly be due to the low levels of
Extraversion and Openness to Experience observed in our sample of patients with
hearing loss.
PMID- 29939863
TI - SHANK3 variant as a cause of nonsyndromal autism in an 11-year-old boy and a
review of published literature.
AB - Autism spectrum disorder (ASD) encompasses a spectrum of pervasive
neuropsychiatric disorders characterized by deficits in social interaction,
communication, unusual and repetitive behaviours. The aetiology of ASD is
believed to involve complex interactions between genetic and environmental
factors; it can be further classified as syndromic or nonsyndromic, according to
whether it is the primary diagnosis or secondary to an existing condition where
both common and rare genetic variants contribute to the development of ASD or are
clearly causal. The prevalence of ASD in children is increasing with higher rates
of diagnosis and an estimated one in 100 affected in the UK. Given that
heritability is a major contributing factor, we aim to discuss research findings
to-date in the context of a high-risk autism candidate gene, SHANK3 (SH3 and
multiple ankyrin repeat domain 3), with its loss resulting in synaptic function
disruption. We present a 10-year-old patient with a pathogenic de novo
heterozygous c.1231delC, p.Arg411Val frameshift variant in SHANK3. He presented
with severe autism, attention deficit hyperactivity disorder and pathological
demand avoidance, on a background of developmental impairment and language
regression. The number of genes associated with autism is ever increasing. It is
a heterogeneous group of disorders with no single gene conferring pathogenesis in
the majority of cases. Genetic abnormalities can be detected in ~15% of ASD and
these range from copy number variants in 16p11.2 and 15q13.2q13.3 to several well
known genetic disorders including tuberous sclerosis and fragile X syndrome.
Further, high confidence autism genes include but are not limited to NRXN, NLGN3,
NLGN4, SHANK2 and SHANK3.
PMID- 29939864
TI - Interstitial lung abnormalities: prognostic stratification of subtle radiological
findings.
AB - PURPOSE OF REVIEW: The purpose of this review is to provide the radiological
description of interstitial lung abnormalities (ILA) as an increasingly reported
entity on high-resolution computed tomography (HRCT), and to discuss their
prospective interpretation. RECENT FINDINGS: Elementary findings consistent with
ILA are described on HRCT, yet the diagnostic confidence for the interpretation
of these subtle features might be challenging and further hampered by
interobserver variability. Quantitative analysis is expected to provide
standardized and reproducible description of ILA. There is affinity between ILA
morphology and histopathological pattern, either fibrosis or atypical adenomatous
hyperplasia. Beyond radiology, there are predictors of risk of ILA, such as: age,
smoking habit, circulating biomarkers, and genetic sequencing. ILA with fibrotic
morphology show prognostic impact including progression to interstitial lung
disease, mortality from respiratory disease, and all-cause mortality. The
association between ILA and susceptibility to lung damage further includes the
interlacing connection between interstitial findings and lung cancer, both as a
risk factor for diagnosis and as a predictor of survival. SUMMARY: ILA are a
(minor) finding on HRCT and they should be reported by radiologists for optimal
management within the specific clinic-functional scenario. ILA encompass a number
of semiological characteristics associated with either fibrotic or nonfibrotic
disease.
PMID- 29939865
TI - Nutrition and corticosteroids in the treatment of sarcoidosis.
AB - PURPOSE OF REVIEW: Sarcoidosis is a chronic disease, which is routinely treated
with corticosteroids. Steroid resistance or steroid-induced adverse effects
require alternatives. Other immune-modulating pharmacological treatments have
been developed, and therefore expanded tremendously. Until now, the role of
nutrition in the overall management of sarcoidosis has been neglected although
anti-inflammatory properties of nutritional components have been known for many
years now. New nutritional possibilities emerge from already existing data and
offer new therapeutic avenues in the treatment of sarcoidosis. RECENT FINDINGS:
Various dietary components have been shown to reduce pulmonary inflammatory
processes. It is increasingly recognized, however, that the specificity and
magnitude of the effect of nutrition differs from pharmacological interventions.
Conventional randomized clinical trials are less suitable to test the effect of
nutrition in comparison with testing drugs. Mechanistic knowledge on the action
of dietary components in conjunction with an increasing understanding of the
molecular processes underlying steroid resistance (as investigated in asthma and
COPD and unfortunately hardly in sarcoidosis) lead to exciting suggestions on
combinations of nutrition/nutritional bioactive compounds and corticosteroids
that may benefit sarcoidosis patients. SUMMARY: In order to understand the
effects of nutrition in chronic disease, it is important to elucidate mechanisms
and pathways of effects. Several complementing lines of evidence should be
integrated in order to be able to advise sarcoidosis patients on a healthy diet
as such or in combination with prescribed anti-inflammatory therapy.
PMID- 29939866
TI - Natural History of Structural Hip Abnormalities and the Potential for Hip
Preservation.
AB - Hip osteoarthritis (OA) exerts a significant burden on society, affecting 3% of
Americans aged >30 years. Recent advances in the understanding of the
pathoanatomy and pathomechanics of the hip have led to treatment options for
young adults with hip pain. Femoroacetabular impingement, specifically cam-type
femoroacetabular impingement, hip dysplasia, and the sequelae of pediatric hip
disease can predispose the hip to early OA. However, many patients with abnormal
anatomic findings do not develop early OA, suggesting that there exist other
patient characteristics that are protective despite abnormal bony anatomy.
Outcome studies show that arthroscopic and open hip procedures improve pain and
function in patients with symptomatic hips. However, there is currently limited
evidence that these procedures extend the life of the patient's natural hip.
Additional studies are needed to determine protective or adaptive factors in
patients with abnormal anatomy who do not develop early OA and to determine
whether joint preserving hip surgery extends the life of the native hip joint.
PMID- 29939867
TI - Role of Advanced Imaging in the Diagnosis and Management of Active Legg-Calve
Perthes Disease.
AB - Since the first description of Legg-Calve-Perthes disease a century ago, the
diagnosis, staging, prognosis, and treatment decisions have been based on plain
radiographs. The goal of treatment is prevention of femoral head deformity, yet
radiographic prognostic classifications are applied in the fragmentation stage,
often after deformity occurs. These classifications are assigned too late in the
progression of the disease to maximize the effects of intervention. Thus,
alternative mechanisms to determine femoral head involvement earlier in the
disease course are warranted. Increasingly, MRI has been used in the study of the
disease. Gadolinium-enhanced and diffusion-weighted MRI has shown promising
results that correlate with radiographic classifications and the early
radiographic outcome. Advanced imaging has improved the assessment of hinge
abduction, yet the exact definition remains controversial. The role of imaging in
the management of Legg-Calve-Perthes disease is rapidly evolving. New or refined
imaging techniques may eventually allow earlier prognosis and treatment.
PMID- 29939868
TI - Screening of hepatitis C virus infection in adult general population in Spain.
AB - PURPOSE: The aim was to estimate seroprevalence and prevalence of hepatitis C
virus (HCV) infection in a small health area of the Valencian Community, Spain.
PATIENTS AND METHODS: This is a descriptive cross-sectional study aimed at
estimation of HCV infection prevalence in the whole adult population (25-70 years
old), that is, a pilot study for an eventual population-based screening program.
RESULTS: A total of 5849 participants aged 25-70 years (51% male) were invited to
participate by regular mail. Overall, 143 letters were returned owing to errors
in the addresses. Of 5706 participants, 2637 (46.2%) participated in the study.
Rapid test of anti-HCV antibody detection was positive in 30 cases (HCV
seroprevalence 1.14%, 95% confidence intervals: 0.73-1.55%). Of those, seven were
not aware of their condition. Participants who had a positive result in the rapid
test of anti-HCV detection were given a confirmatory test by enzyme immune assay,
and all had a positive result. RNA-HCV determination by quantitative PCR in
positive anti-HCV patients showed positive viremia in 13 (43.3%) cases, of which
five were not aware of the disease. Of the 17 patients who had negative viremia,
two were unaware of their HCV status, one was a carrier of anti-HCV and was
already aware of his condition, and 14 had been previously treated with
satisfactory results. Regarding fibrosis, of the seven patients who were unaware
of HCV infection, none of them had significant fibrosis. Moreover, 26 (86.7%)
anti-HCV positive patients were reported to have one or more risk factors for HCV
infection. CONCLUSION: HCV screening strategies applied to the general population
are good means to diagnose and treat patients who are not aware of their
infection, avoiding new transmissions as well as disease progression.
PMID- 29939869
TI - Promoting early expression of breast milk in mothers of preterm infants in a
neonatal unit: a best practice implementation project.
AB - OBJECTIVES: The aim of this implementation project was to optimize lactation
success in mothers of preterm infants by ensuring early (as soon as possible and
within six hours) and frequent (eight to 12 times/day) milk expression.
INTRODUCTION: Evidence suggests that breast milk improves enteral feeding
tolerance and neurodevelopmental outcomes and decreases the risk of necrotising
enterocolitis and late onset sepsis in preterm infants. It is widely accepted
that breast milk expression should commence as soon as possible and within six
hours of delivery. RESULTS: Following implementation of the breast milk
expression information pack and staff education program, compliance to clinical
guideline recommendations improved considerably. An increase from 5/20 (25%) to
17/20 (85%) of women expressing milk within six hours of delivery was observed.
The average expression times also increased: from 2.6 (2.0) to 6.1 (2.7) times in
the first 24 hours and from 4.6 (1.7) to 7.8 (1.7) times between 24-48 hours. The
compliance rate for milk expression within six hours of delivery and expression
of eight to 12 times daily in the first 48 hours increased from 1/20 (5%) at
baseline to 10/20 (50%) in the follow-up audit. CONCLUSION: The implementation of
the breast milk information pack and staff education led to improvements in the
milk expression practices of mothers who had preterm infants. As a result of this
project, the information packs are now routinely given to all women at risk of
delivering preterm or who have babies in the neonatal unit. Further audits will
be undertaken in the future to determine sustainability of practice changes.
PMID- 29939870
TI - Abdominal Obesity is More Predictive of Advanced Colorectal Neoplasia Risk Than
Overall Obesity in Men: A Cross-sectional Study.
AB - GOALS: We aimed to ascertain whether waist circumference (WC) is associated with
risk of colorectal neoplasia (CRN), independent of body mass index (BMI).
BACKGROUND: Although several studies have reported the association between
abdominal obesity, measured by WC, and CRN, it remains unclear whether their
association is biased by BMI. STUDY: A cross-sectional study was performed on
154,552 asymptomatic examinees who underwent colonoscopy for a health check-up.
RESULTS: The mean age was 42.6 years, and the proportion of males was 65.2%. The
prevalence rate of CRN in subjects in WC quartiles 1, 2, 3, and 4 was 15.6%,
18.1%, 20.4%, and 22.0% among men and 7.8%, 9.4%, 12.2%, and 15.8% among women,
respectively. WC and BMI were independent risk factors for overall CRN and
nonadvanced CRN in both men and women. In men, the association of BMI with
advanced CRN was attenuated to null after adjusting for WC [Q2, Q3, and Q4 vs.
Q1; odds ratios (95% confidence intervals), 0.93 (0.79-1.10), 0.85 (0.71-1.03),
and 0.99 (0.80-1.22), respectively; Ptrend=0.822], whereas the association of WC
with advanced CRN significantly persisted even after adjusting for BMI [Q2, Q3,
and Q4 vs. Q1; 1.20 (1.02-1.42), 1.45 (1.20-1.75), and 1.64 (1.32-2.04),
respectively; Ptrend<0.001]. In women, neither WC nor BMI was associated with the
risk of advanced CRN. CONCLUSIONS: Abdominal obesity is associated with an
increased risk of advanced CRN, independent of overall obesity (BMI) in men. Our
findings suggest that abdominal obesity is more strongly predictive of advanced
CRN than overall obesity in men.
PMID- 29939871
TI - Amputation Outcomes in Congenital Pseudarthrosis of the Tibia.
AB - BACKGROUND: Successful radiographic union in the treatment of congenital
pseudarthrosis of the tibia (CPT) may be complicated by persistent pain,
recurrent fracture, and poor function necessitating further intervention,
including amputation. The long-term functional, radiographic, and clinical
outcomes of patients who have undergone amputation as treatment for CPT are
unknown. METHODS: A retrospective study of patients with a diagnosis of CPT
secondary to neurofibromatosis and eventual treatment with amputation were
included. Clinical and radiographic data, including initial Crawford
classification, type of amputation, subsequent operative procedures, and evidence
of radiographic healing were collected. RESULTS: A total of 17 patients with a
mean age of 4.5 years (range, 0.7 to 9.2 y) at the time of amputation met
inclusion criteria. Clinical follow-up averaged 11.1 years (range, 2.1 to 18.4
y), with radiographic follow-up averaging 9.1 years (range, 2.1 to 16.4 y). The
mean number of surgeries before amputation was 2.2 procedures. Four patients
underwent amputation as the primary procedure (3 Boyd, 1 below knee amputation
(BKA)). At the time of amputation, a Boyd amputation was performed in 13 patients
with stabilization of the pseudoarthrosis achieved with retrograde Rush rodding
of the tibia and local autograft. A transtibial amputation (BKA) was performed in
4.After the Boyd procedure, 4 of the 13 patients (31%) demonstrated persistent
nonunion of the pseudoarthrosis and required secondary procedures to gain union.
At the most recent follow-up, 12 of 13 patients demonstrated successful
radiographic healing of the pseudoarthrosis. Two patients, one for persistent
pain and the other for refracture, were later converted to a BKA during the late
teen years. All patients functioned well with the use of prosthetic devices.
CONCLUSIONS: Union of the pseudoarthrosis occurred in >90% of cases following
amputation. However, secondary procedures were required in 13 of the 17 patients
(76%). Early amputation in the treatment of CPT provides a stable extremity and
potential for a high level of function with the use of an adequate prosthesis.
LEVEL OF EVIDENCE: Level IV-case series.
PMID- 29939872
TI - Homocysteine sensitizes the mouse neuromuscular junction to oxidative stress by
nitric oxide.
AB - Homocysteine (HCY), a redox-active metabolite of the methionine cycle, is of
particular clinical interest because of its association with various
neurodegenerative diseases including amyotrophic lateral sclerosis. It has been
previously established that HCY exacerbates damage to motor neurons from reactive
oxygen species (ROS) such as hydrogen peroxide. To assess the role of HCY at the
mammalian neuromuscular junction, neurotransmission was monitored by
electrophysiology at the mouse epitrochleoanconeus muscle. Preparations were
preincubated in HCY before inducing ROS and recordings were taken before and
after ROS treatment. In this study, HCY was observed to sensitize the
neuromuscular junction to ROS-induced depression of spontaneous transmission
frequency, an effect we found to be mediated by a N-methyl-D-aspartate receptor
(NMDAR) and nitric oxide (NO). The NMDAR antagonist D, L-2-amino-5
phosphonopentanoic acid prevented the HCY-induced sensitization to oxidative
stress. Disrupting NO activity with either the nitric oxide synthase I antagonist
Nomega-nitro-L-arginine methyl ester hydrochloride or the NO scavenger 2-(4
carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide potassium salt also
prevented sensitization. Moreover, replacing HCY with the exogenous NO donor
Diethylamine NONOate diethylammonium was sufficient to reconstitute the effects
of HCY-induced sensitization to ROS. Interestingly, a novel secondary effect was
observed where HCY itself depresses quantal content, an effect found to be
mediated by NMDARs independently of nitric oxide and ROS. Collectively, these
data present a novel model of two distinct pathways through which HCY alters
neurotransmission at the neuromuscular junction. Characterizing HCY's mechanism
of action is of particular clinical relevance as many treatments for amyotrophic
lateral sclerosis are centered on mitigating HCY-induced pathologies.
PMID- 29939873
TI - Who Leaves Early? Factors Associated With Against Medical Advice Discharge During
Alcohol Withdrawal Treatment.
AB - OBJECTIVE: To determine if certain patient, clinical, and disease factors are
associated with against medical advice (AMA) discharge among patients admitted
for treatment of alcohol withdrawal. METHODS: Data from admissions to a dedicated
unit for treatment of substance withdrawal were collected over a 6-month period.
Patients with AMA and planned discharge were compared with regard to
demographics, clinical data, and substance use disorder disease characteristics.
A stepwise logistic regression was used to find the best model. RESULTS: The
study population included 655 patient encounters. A total of 93 (14%) discharges
were AMA. Bivariate analysis showed patients with AMA discharge were younger
(mean age 43 vs 46 years; P < 0.05), more likely to leave on a Tuesday to
Thursday, and to have an initial withdrawal score at or above the median (AMA 69%
vs planned 56%; P = 0.02). Emergency department (ED) admissions had an AMA
discharge rate of 21% compared with 10% of community admissions (P < 0.05).
Regression analysis found AMA discharge was significantly associated with
admission from the ED (odds ratio [OR] 2.03, confidence interval [CI] 1.27-3.25)
and younger age (OR 0.97, CI 0.95-0.99). There was no significant difference in
discharge disposition among patients with concurrent opioid use disorder who were
on opioid agonist therapy. CONCLUSIONS: AMA discharges occurred in 1 of every 7
admissions. Being admitted from the ED and younger age was associated with AMA
discharge. No other patient or clinical factors were found to be associated with
AMA discharge.
PMID- 29939874
TI - Patients With Substance Use Disorders Leaving Against Medical Advice: Strategies
for Improvement.
AB - : In this issue of the Journal of Addiction Medicine, 2 studies fill an important
gap in knowledge by examining predictors of leaving against medical advice from
inpatient withdrawal management settings. The studies identify important risk
factors for leaving against medical advice and highlight important areas for
inpatient withdrawal management. These include the use of substance specific
standardized protocols and initiation of opioid agonist treatment instead of
opioid detoxification given harms associated with opioid withdrawal. Further need
for increased training in addiction medicine for primary care physicians, and use
of inpatient addiction medicine consult services as part of early intervention
for substance withdrawal are also discussed.
PMID- 29939875
TI - Predictors of Leaving an Inpatient Medical Withdrawal Service Against Medical
Advice: A Retrospective Analysis.
AB - OBJECTIVES: The purpose of this study was to determine the frequency and
predictors of patients leaving an inpatient medical withdrawal unit against
medical advice (AMA). METHODS: This study used a case-control design to compare
patients who were discharged AMA (n = 164) with those who completed treatment (n
= 678). Logistic regression analysis was used to determine which variables were
independent predictors of patients leaving AMA. RESULTS: We found that being
admitted through the emergency department (odds ratio [OR] 3.17, confidence
interval [CI] 1.66-6.08), having gamma-hydroxybutyrate (OR 7.61, CI 1.81-32.09)
as a primary substance of concern compared to alcohol, and having multiple axis I
psychiatric diagnoses (OR 2.20, CI 1.16-4.18) or depression (OR 2.86, CI 1.32
6.17) compared with no psychiatric diagnosis increased the odds of leaving
inpatient medical withdrawal AMA. By contrast, not being dependent on nicotine
(OR 0.45, CI 0.23-0.88) and increasing time since admission (OR 0.42, CI 0.36
0.48) reduced the odds of leaving AMA. CONCLUSIONS: The findings of this study
reveal novel information about patients who leave inpatient medical withdrawal
AMA and can inform targeted interventions to prevent vulnerable patients from
terminating treatment early and improve healthcare service utilization.
PMID- 29939876
TI - Incidence of Basal Cell Carcinoma and Squamous Cell Carcinoma in Patients on
Antiprogrammed Cell Death-1 Therapy for Metastatic Melanoma.
AB - Systemic melanoma therapies have the potential to affect basal cell carcinoma
(BCC) and cutaneous squamous cell carcinoma (cuSCC) development. In this study,
we aim to compare the incidence of BCC and cuSCC in patients with metastatic
melanoma treated with antiprogrammed cell death-1 (anti-PD1), BRAF inhibitor
(BRAFi) monotherapy or dabrafenib and trametinib combination therapy (CombiDT)
with a group of control patients having similar risk factors. We reviewed the
records of melanoma patients on anti-PD1, BRAFi, or CombiDT, and patients from
the High-Risk Melanoma Clinic, Westmead Hospital. We also performed an
immunohistochemical analysis of BCCs under anti-PD1 compared with controls using
PD1, PD-L1, CD3, CD8, and CD20 stains. For the results, in all, 340 patients were
included; 82 on anti-PD1, 134 on BRAFi, 69 on CombiDT, and 55 controls. BRAFi had
the highest incidence of BCC (12.7%), followed by CombiDT (10.1%) and anti-PD1
(2.4%). The incidence of BCC was significantly lower in patients on anti-PD1
(2.4% vs. 19.4%; P<0.001) compared with controls. Patients on anti-PD1 were 8.54
times less likely to develop BCC than the controls [hazard ratio, 0.117 (95%
confidence interval, 0.026-0.526), P=0.005]. BRAFi and CombiDT showed no
significant differences in BCC incidence compared with controls. BRAFi had the
highest cuSCC incidence (23.9%), followed by anti-PD1 (7.3%) and CombiDT (2.9%).
The incidence of cuSCC was significantly higher in patients on BRAFi (23.9% vs.
3.5%; P<0.001) compared with controls, but anti-PD1 and CombiDT showed no
differences in cuSCC incidence compared with controls. Immunohistochemistry
analysis of 10 BCC from under anti-PD1 and 8 BCC from controls patients showed
that while all BCC had negative PD-L1 staining, the percentage of PD1 staining in
anti-PD1 group is significantly lower than that of the control group (independent
t test, 8% vs. 26%; P<0.001). In conclusion, our study suggests that anti-PD1
therapy decreases the incidence of BCC, as a result of the PD1/PD-L1 blockade.
Future studies investigating the role of anti-PD1 in suppressing or treating BCC
may be warranted.
PMID- 29939877
TI - Cytokine Release Syndrome During Sequential Treatment With Immune Checkpoint
Inhibitors and Kinase Inhibitors for Metastatic Melanoma.
AB - Switching from immunotherapy to targeted therapy in metastasized melanoma can be
complicated by a cytokine release syndrome (CRS). CRS is a serious complication,
which is induced by high levels of circulating cytokines, associated with T-cell
engagement and proliferation, and results in a constellation of symptoms with
variable organ involvement. We report 2 patients with BRAF V600 mutant melanoma
who were previously treated with anti-PD-1+/-anti-LAG-3 antibodies and were
switched to BRAF/MEK-inhibitors because of progressive disease. Both cases depict
the complexity of interactions occurring during sequential treatment with immune
checkpoint inhibitors and kinase inhibitors. Early identification and management
of CRS is crucial to decrease its toxicity and improve safety of further drugs to
be given in a therapeutic ladder.
PMID- 29939878
TI - Management of the Critically Ill Adult Chimeric Antigen Receptor-T Cell Therapy
Patient: A Critical Care Perspective.
AB - OBJECTIVES: Chimeric antigen receptor T-cell therapy, a type of immune effector
therapy for cancer, has demonstrated encouraging results in clinical trials for
the treatment of patients with refractory hematologic malignancies. Nevertheless,
there are toxicities specific to these treatments that, if not recognized and
treated appropriately, can lead to multiple organ failure and death. This article
is a comprehensive review of the available literature and provides, from a
critical care perspective, recommendations by experienced intensivists in the
care of critically ill adult chimeric antigen receptor T-cell patients. DATA
SOURCES: PubMed and Medline search of articles published from 2006 to date. STUDY
SELECTION: Clinical studies, reviews, or guidelines were selected and reviewed by
the authors. DATA EXTRACTION: Not available. DATA SYNTHESIS: Not available.
CONCLUSIONS: Until modifications in chimeric antigen receptor T-cell therapy
decrease their toxicities, the intensivist will play a leading role in the
management of critically ill chimeric antigen receptor T-cell patients. As this
novel immunotherapeutic approach becomes widely available, all critical care
clinicians need to be familiar with the recognition and management of
complications associated with this treatment.
PMID- 29939879
TI - Dynamic Hyperinflation Impairs Cardiac Performance During Exercise in COPD.
AB - PURPOSE: To investigate the correlation between a plateau in minute ventilation
VE during cardiopulmonary exercise tests (CPETs) and its impact on cardiac
performance. METHODS: This retrospective study analyzed 2575 CPETs of patients
with chronic obstructive pulmonary disease. The study randomly selected 10
patients with a plateau in the VE curve, suggesting dynamic hyperinflation, 10
patients with normal pattern for the VE curve, and 10 healthy persons. Classic
CPET variables, the new ventilation hyperinflation index, and the dynamic cardiac
constraint index were analyzed. RESULTS: The patients with dynamic hyperinflation
presented with lower ventilation at 100% work rate (P < .0001), without
significant differences in VE at 50% and 100% work rate. Patients with dynamic
hyperinflation also presented with a lower oxygen pulse (O2 pulse) at 100% (P <
.0001), without significant difference in O2 pulse at 50% and 100% work rate. The
subjects with dynamic hyperinflation had a higher ventilation hyperinflation
index (P < .0001) and dynamic cardiac constraints index (P < .0001). The
ventilation hyperinflation index correlated with the dynamic cardiac constraints
index (r = 0.81, P < .0001); oxygen pulse variation (r =-0.63, P < .001); VE/VCO2
slope (r =-0.57, P < .01); work rate (r =-0.86, P < .0001); VO2 (r =-0.80, P <
.0001), and VE (r =-0.83, P < .0001). CONCLUSION: There is a correlation between
a plateau in the VE during CPET, suggesting hyperinflation, and it has an impact
on cardiac performance.
PMID- 29939880
TI - Spontaneous Coronary Artery Dissection (SCAD): FEMALE SURVIVORS' EXPERIENCES OF
STRESS AND SUPPORT.
AB - PURPOSE: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic
type of acute myocardial infarction that primarily affects young, healthy women
without typical risk factors for heart disease. Few investigations have examined
psychosocial variables in this population and none have looked at patient
perceptions of the experience and stresses associated with having a SCAD event or
the resources currently available to SCAD survivors. This investigation describes
survivors' subjective experiences of SCAD. Participants also provided information
about types and helpfulness of resources available to them post-SCAD, including
cardiac rehabilitation. METHODS: Participants were recruited online and completed
a one-time questionnaire. RESULTS: Participants (n = 409) completed a
questionnaire concerning their experiences with their SCAD event in the 1 y and 2
wk prior to the SCAD event. Their responses reflected moderate to high
perceptions of stress. Participants experienced the SCAD event as highly
stressful and frightening and their heart health presents as a moderate-severe
source of current, post-diagnosis stress. Spontaneous coronary artery dissection
based informational support was frequently rated as inadequate, whereas other
supportive resources varied in their helpfulness and accessibility. Participants
reported positive experiences in cardiac rehabilitation and strong interest in
SCAD-specific, professionally led, online patient education and support groups.
CONCLUSIONS: This study is the largest to date investigation of SCAD survivors
and their experiences in this understudied and perhaps underrecognized condition.
Opportunities for researchers and providers to develop, tailor, and disseminate
SCAD-specific interventions are discussed.
PMID- 29939881
TI - Mothers at Risk: Factors Affecting Maternal Postpartum Length of Stay.
AB - Perinatal complications linked to maternal comorbidities contribute to increased
healthcare utilization through an extended postpartum length of stay (LOS).
Understanding factors influencing postpartum LOS may minimize the adverse effects
associated with comorbidities and complications. The purpose of this study was to
identify risk factors with the greatest odds of increasing postpartum LOS. Linked
2008-2009 hospital discharge and birth certificate data were used to examine
comorbidities and complication codes in 1 015 424 births. The overall rate for an
extended LOS (vaginal: >5 days/cesarean: >6 days) was 3.63 per 1000 live births.
Complications were present in 17% of pregnancies; multiple complications were
seen in 1%. Chronic hypertension was associated with an extended stay for both
vaginal and cesarean births (odds ratio [OR] = 5.89 [95% CI, 4.39-7.88]; OR =
3.57 [95% CI, 3.05-4.17], respectively). Puerperal infections (OR = 6.86 [95% CI,
5.73-8.21]), eclampsia (OR = 17.07 [95% CI, 13.76-21.17]), and transfusions (OR =
11.66 [95% CI, 9.20-14.75]) occurred most frequently and conferred the highest
odds of an extended stay for vaginal births. Cerebrovascular conditions (OR =
15.32 [95% CI, 11.90-19.60]) and infection (OR = 15.35 [95% CI, 10.11-23.32])
conferred the highest odds of an extended LOS for cesarean births. The earlier
risk factors are recognized, the sooner processes can be initiated to optimize
organizational preparation, thus decreasing adverse maternal outcomes and
extended hospital stays.
PMID- 29939882
TI - Caring about Preemies' Safe Sleep (CaPSS): An Educational Program to Improve
Adherence to Safe Sleep Recommendations by Mothers of Preterm Infants.
AB - Preterm infants born before 37 weeks' gestation die of sudden infant death
syndrome (SIDS) at a rate more than double that of term infants. There is a need
for SIDS prevention programs tailored to the specific needs of parents of high
risk infants. The purpose of this study was to pilot test an online educational
module addressing SIDS risk-reduction recommendations (RRRs) for parents of
preterm infants. This study was conducted in a 44-bed transitional care unit at a
level IV NICU in the Midwest. A repeated-measures design was used. Two weeks
before discharge, mothers completed a survey, addressing knowledge and plans for
caring for their baby at home. Mothers then viewed the 5-section Caring about
Preemies' Safe Sleep (CaPSS) education module and completed the postmodule
evaluation. A discharge survey was completed 4 weeks postdischarge. Fifteen
mothers, mean age 26.4 years, participated; 8 (53%) returned the postdischarge
survey. Module evaluation rated clarity and completeness of information high.
Mothers' ratings of SIDS knowledge were significantly higher after viewing the
module (P = .000) and 4 weeks after discharge home (P = .012). Mothers found the
use of a pacifier at sleep times to be new information and changed their plans
for caring for their infant, with 28.6% of mothers always offering a pacifier
before sleep after discharge compared with the 6.7% who had planned to do this
before discharge. However, only 71% of infants slept in parents' room after
discharge and only 41% were receiving at least some breast milk, which are not
consistent with SIDS RRRs.
PMID- 29939884
TI - Design Thinking: Can it enhance nursing research?
PMID- 29939883
TI - Optimal timing of fluorine-18-fluoromisonidazole positron emission
tomography/computed tomography for assessment of tumor hypoxia in patients with
head and neck squamous cell carcinoma.
AB - OBJECTIVES: The aim of this study was to identify the optimal timing of fluorine
18-fluoromisonidazole (F-MISO) PET/CT imaging to assess hypoxia in patients with
head and neck squamous cell carcinoma. PATIENTS AND METHODS: Eighteen patients
underwent pretreatment F-MISO PET/CT imaging after providing written informed
consent. PET scans were acquired at 1, 3, and 5 h after injection of the
radionuclide. The mean standardized uptake value (SUV) within a spherical region
of interest placed on the contralateral neck musculature at the level of the
largest tumor dimension was labeled as background. A value 1.5 times the
background was deemed the threshold for significant hypoxia. Using this
threshold, volumetric regions of interest encompassing the tumor were placed and
hypoxic tumor volume (HTV) was generated for the primary tumor. Repeated-measures
analysis of variance was used to compare the F-MISO PET/CT metrics across the
three time-points. The volume of the primary tumor was also correlated with HTV.
RESULTS: The mean SUV of the background decreased consistently over time,
resulting in increased focality of F-MISO uptake in the tumor tissues. Analysis
of variance showed statistically significant differences in the mean SUV
measurements of the background between the 1-h and the 3-h time-points (P=0.034)
as well as the 1-h and the 5-h time-points (P=0.034). In parallel, the mean HTV
increased from 1.72 cm at 1 h after injection to 6.52 cm at 3 h and further to
7.24 cm at 5 h, with a statistically significant difference between the 1-h and
the 3-h scans (P=0.023) and the 1-h and the 5-h scans (P=0.023). There was a
moderately good positive correlation between gross tumor volume on planning
computed tompography (CT) and HTV at 3 h on the F-MISO scan (Pearson's
correlation co-efficient 'r'=+0.753; P<0.0001). CONCLUSION: The contrast
resolution of F-MISO PET/CT scans in head and neck squamous cell carcinoma is
suboptimal with early image acquisition, but improves significantly after delayed
imaging. Increasing volume of tumor at the primary site is associated with an
increase in hypoxia.
PMID- 29939885
TI - Effect of Polyhexamethylene Biguanide Solution on Bacterial Load and Biofilm in
Venous Leg Ulcers: A Randomized Controlled Trial.
AB - PURPOSE: The purpose of this study was to investigate the effect of
polyhexamethylene biguanide (PHMB) solution as a wound cleanser on bacterial load
and bacterial biofilm in venous leg ulcers. DESIGN: Randomized controlled trial.
SUBJECTS AND SETTING: The target population was adults attending the dermatology
outpatient clinic of the Clinical Hospital of the Federal University of Minas
Gerais, Brazil. The sample comprised 44 patients with venous leg ulcers recruited
over a 6-month period. METHODS: Participants were divided into 2 groups: the
intervention group had their wounds cleansed with PHMB, and the control group had
their wound cleansed with a 0.9% saline solution. Tissue fragments of the wounds
were collected for bacteriological analysis; transmission electron microscopy was
used to identify the presence of biofilm. RESULTS: The bacterial load was reduced
in both groups compared to baseline values; no significant difference was found
when groups were compared. Correlation analysis between wound duration (months),
wound area (cm2), necrosis (%), variables, and bacterial count (colony forming
units [CFUs]/g) after cleansing showed a significant relationship between area of
the wound and CFUs/g (P = .0070, r = 0.51). Transmission electron microscopy
revealed the presence of bacterial biofilm in the wounds after cleansing with
both solutions. CONCLUSIONS: The results of this study indicate that both PHMB
and saline solution are effective in reducing the bacterial load in venous leg
ulcers. However, bacterial biofilm was present after cleansing with both
solutions. These findings provide important evidence regarding effectiveness of 2
common wound cleansers on bacterial presence in wounds.
PMID- 29939886
TI - Perforation of Palate in Granulomatosis With Polyangiitis.
PMID- 29939887
TI - Malignant Multiple Myeloma of the Pleura.
PMID- 29939888
TI - Convex Probe EBUS-guided Fiducial Placement for Malignant Central Lung Lesions.
AB - BACKGROUND: Stereotactic body radiotherapy (SBRT) had become a therapeutic
modality in patients with primary tumors, locally recurrent as well as
oligometastasis involving the lung. Some modalities of SBRT require fiducial
marker (FM) for dynamic tumor tracking. Previous studies have focused on
evaluating bronchoscopic-guided FM placement for peripheral lung nodules. We
describe the safety and feasibility of placing FM using real-time convex probe
endobronchial ultrasound (CP-EBUS) for SBRT in patients with centrally located
hilar/mediastinal masses or lymph nodes. METHODS: This is a retrospective review
of patients who were referred to Beth Israel Deaconess Medical Center's
multidisciplinary thoracic oncology program for FM placement to pursue SBRT.
RESULTS: Thirty-seven patients who underwent real-time CP-EBUS were included.
Patients had a median age of 71 years [interquartile range (IQR), 59.5 to 80.5].
The median size of the lesion was 2.2 cm (IQR, 1.4 to 3.3 cm). The median
distance from the central airway was 2.4 cm (IQR, 0 to 3.4 cm). A total of 51 FMs
(median of 1 per patient) were deployed in 37 patients. At the time of SBRT
planning, 46 (90.2%) were confirmed radiologically in 32 patients. Patients with
unsuccessful fiducial deployment (n=5) underwent a second procedure using the
same technique. Of those, 3 patients had a successful fiducial placement via
bronchoscopy, 1 patient required FM placement by percutaneous computed tomography
guided approach and 1 patient required FM placement through EUS by
gastroenterology. CONCLUSION: CP-EBUS-guided FM placement for patients with
malignant lymph nodes and central parenchymal lung lesions appears to be safe and
feasible.
PMID- 29939889
TI - A review and study of aspirin utilization for the primary prevention of
cardiovascular events in a psychiatric population.
AB - In April 2016, the US Preventive Service Task Force (USPSTF) updated the aspirin
guidelines for the primary prevention of cardiovascular disease (CVD) and
colorectal cancer. This review assesses the importance of appropriate use of
aspirin for the primary prevention of CVD and, specifically, how individuals with
psychiatric disorders may benefit from such use. This study examined how current
prescribing practices of aspirin in a state psychiatric hospital align with these
new guidelines and how inappropriate prescribing may jeopardize patient safety. A
retrospective chart review of 93 patients was performed to evaluate whether
aspirin therapy would be recommended for primary prevention of CVD based on the
new USPSTF guidelines. A secondary analysis of these data was performed using the
2009 USPSTF recommendations to strengthen the assumption that practitioners were
no longer using the old guidelines. Drug interactions between aspirin and
concurrently prescribed pharmacotherapy were classified based on of severity, and
the past events of bleeding were quantified. Based on the 2016 guidelines, 25 of
the 93 patients included in this study were identified as potential candidates
who would benefit from aspirin use for the primary prevention of CVD; of whom 22
(88%) were not prescribed aspirin. The remaining 68 patients did not meet the
criteria for aspirin use for primary prevention, although 11 (16.2%) of these
patients were taking low-dose aspirin. Based on the 2009 guidelines, 49 of the 93
patients included in our study would have been identified as potential candidates
who would benefit from the use of aspirin for the primary prevention of CVD; 41
(83.7%) of whom were not prescribed aspirin. The remaining 44 patients did not
meet the previous criteria for aspirin use for primary prevention, although six
(13.6%) of these individuals were taking low-dose aspirin daily. The results
above indicate a difference between prescribing practices of aspirin use for the
primary prevention of CVD. We identified a similar rate of underuse; however,
there was a slight increase in the appropriate prescribing according to the 2016
guidelines compared with the 2009 guidelines (88 vs. 83.7%, respectively). Also,
there was a higher incidence of unnecessary prescribing (overutilization) of
aspirin for the primary prevention of CVD in 2016 compared with 2009 despite the
more restrictive criteria (and smaller candidate pool) published in these newer
guidelines. There were 47 drug interactions identified when patients' aspirin and
concurrent medication regimens were reviewed for our entire sample population.
These interactions could potentially lead to an adverse drug reaction in the
future. Our safety analysis revealed that none of the patients who were
prescribed aspirin had any bleeding events while on therapy within the period of
this study. Inappropriate omission of aspirin (underutilization) was more
prevalent in our psychiatric institution than overutilization; however, the
overall percentage of both underuse and overuse were greater when patients were
evaluated according to the 2016 guidelines and then compared with the 2009
statistics. Overutilization did not pose a serious risk for those on aspirin
therapy in this sample, as there were no major episodes of bleeding. However,
future harm from aspirin still exists based on the significant number of major
and moderate potential drug interactions with aspirin and the increased risk of
decreased adherence to critical psychiatric medications due to increased pill
burden and regimen complexity. Our findings demonstrate that there is an
opportunity to educate prescribers on the updated 2016 USPSTF guidelines to
improve preventive care and patient safety, which include harm reduction by
initiating aspirin in those who are at a risk of cardiovascular events,
continuing aspirin in those who are currently receiving aspirin appropriately,
and discontinuing aspirin in those who are not considered to be at a high risk of
CVD and who may also be at a risk of experiencing an increased risk of bleeding.
PMID- 29939891
TI - Stair climbing exercise as a novel health intervention for menopause:
cardiovascular and skeletal muscle implications.
PMID- 29939890
TI - The conundrum of depression clinical trials: one size does not fit all.
AB - In this paper we review the history of antidepressant (AD) development, since the
discovery of imipramine in 1957 to the present day. Through this exploration we
will show that the increasing placebo response is likely a red herring and that a
higher magnitude of placebo response is not an adequate explanation for AD
trials' high failure rates. As a better explanation for their lack of success, we
will examine some of the fundamental flaws of AD clinical trials and their
origins in historical forces. We focus on underpowering, which occurs as a
consequence of unrealistic expectations for AD performance. In addition, we
describe the lack of precision in the depression outcome measurements for the
past 40 years and show how these measures contrast with those used in clinical
trials of other chronic diseases, which use simpler outcome measures. Finally, we
describe the role of regulatory agencies in influencing clinical trial design and
how the assumption that 'one size fits all' for the past 60 years has led to
flawed design of AD clinical trials.
PMID- 29939892
TI - Factors associated with knowledge about menopause and hormone therapy in middle
aged Brazilian women: a population-based household survey.
AB - OBJECTIVES: The aim of the study was to evaluate knowledge about menopause and
hormone therapy (HT) among middle-aged Brazilian women and identify the factors
associated with the level of knowledge. METHODS: A cross-sectional study was
conducted with 749 women aged 45 to 60 years, residing in the Metropolitan Region
of Campinas, Brazil. The dependent variable was knowledge about menopause and HT
evaluated using a numerical score based on the answers given to three questions
that had several response options. The independent variables were
sociodemographic characteristics, personal habits, and health conditions.
Statistical analysis was carried out by Mann-Whitney, Kruskal-Wallis, and a
generalized linear model. RESULTS: The mean age was 52.5 (+/-4.4) years. Most of
the women were postmenopausal (68%) and 19.5% had a history of current or
previous use of HT. The final score for knowledge about menopause ranged from +1
to +11, with a mean of 4.59 (+/-1.86) and a median of 4. Women with higher levels
of schooling (coefficient = 0.64, P < 0.001); with higher socioeconomic status
(coefficient = 0.47, P < 0.002); with vaginal dryness (coefficient = 0.47, P =
0.003); who consumed alcohol (coefficient = 0.61, P = 0.006); who use or had ever
used any type of treatment to counteract menopausal symptoms (coefficient = 0.41,
P = 0.008); with anxiety (coefficient = 0.35, P = 0.037); and with depression
(coefficient = 0.31, P = 0.043) possessed greater knowledge about menopause and
HT. Women with a higher number (>=3) of vaginal deliveries (coefficient = -0.61,
P < 0.001) and a higher body mass index (coefficient = -0.02, P = 0.046)
possessed less knowledge about menopause and HT. CONCLUSIONS: The knowledge about
menopause and HT demonstrated by the interviewees was low and possibly related to
the time of exposure to qualified information.
PMID- 29939893
TI - Prostate-specific membrane antigen for prostate cancer theranostics: from imaging
to targeted therapy.
AB - PURPOSE OF REVIEW: In recent years, major advances in molecular imaging of
prostate cancers (PCa) were made with the development and clinical validation of
highly accurate PET tracers to stage and restage the disease. Prostate-specific
membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and
its expression has led to the development of PSMA-binding radiopharmaceuticals
for molecular imaging or radioligand therapy (RLT). We herein review the recent
literature published on diagnostic and therapeutic (i.e. theranostic) PSMA
tracers. RECENT FINDINGS: Development in small PSMA-targeted molecules labeled
with gallium-68 and fluorine-18 show promising results for primary staging and
detection of disease at biochemical recurrence using PET/computed tomography
(PET/CT). Studies show a higher sensitivity and specificity, along with an
improved detection rate over conventional imaging (CT scan and bone scan) or
choline PET tracers, especially for restaging after prostate-specific antigen
failure following loco-regional therapy. In addition, some PSMA tracers can be
labeled with beta-minus and alpha particle emitters, yielding encouraging
response rates and low toxicity, and potentially offering a new line of targeted
therapy for metastatic castration-resistant PCa. SUMMARY: PSMA-targeted tracers
have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given
their specific biodistribution toward PCa tissue, PSMA RLT now offers new
therapeutic possibilities to target metastatic PCa. Prospective multicenter
randomized studies investigating the clinical impact of PSMA-targeted molecules
are urgently needed.
PMID- 29939894
TI - No Clinically Important Difference in Pain Scores After THA Between Periarticular
Analgesic Injection and Placebo: A Randomized Trial.
AB - BACKGROUND: Periarticular analgesic injection (PAI) is being used more commonly
for pain relief after orthopaedic surgeries. However, there is conflicting
evidence regarding the effectiveness of PAI for post-THA pain relief.
QUESTIONS/PURPOSES: In a double-blind, randomized, controlled trial among
patients undergoing same-day bilateral THA, with each patient serving as his or
her own control, we asked: (1) Did the pain score as measured on a 100-mm VAS
differ between the hips that received PAI versus placebo? (2) Were there
differences in complications between the treatment and control hips in these
patients? METHODS: Over a 1-year period at one center, 45 patients underwent same
day bilateral THA; three were excluded for prespecified reasons, and two declined
participation in this randomized, controlled trial, leaving 40 patients (80 THAs)
in the study. Patients randomly received PAI in one hip and placebo in the
contralateral hip; patients, surgeons, and nurses were blinded in terms of which
hip received the PAI and which hip received a placebo saline injection. The PAI
solution included ropivacaine, morphine hydrochloride hydrate,
methylprednisolone, ketoprofen, and epinephrine. The primary outcome was the VAS
for pain at rest 24 hours after THA, measured using a 100-mm horizontal VAS. The
VAS score was compared between two groups and assessed to reach the reported
threshold values for the minimum clinically important difference (MCID) of 20 mm
for the postoperative VAS score. No patients were lost to followup, and there
were no missing data for the primary outcome. Complications that occurred during
the trial were recorded prospectively with emphasis on infection, wound
complications, nerve palsy and allergic reactions to the injections. RESULTS:
There were no clinically important differences between hips treated with the PAI
and those treated with the placebo injection at any point. The hips that received
PAI had less pain than those receiving placebo 24 hours after THA (16 +/- 17 mm
versus 22 +/- 20 mm; mean difference, 6 mm; 95% confidence interval [CI], 2-9 mm;
p = 0.006), but this effect size was below the MCID of 20 mm and thus is unlikely
to be clinically important. The hips that received PAI also had better VAS scores
in the recovery room (38 +/- 29 mm versus 52 +/- 33 mm; mean difference 14 mm;
95% CI, 5-23 mm; p = 0.004) and 3 hours after THA than placebo controls (28 +/-
22 mm versus 37 +/- 24 mm; mean difference 9 mm; 95% CI, 2-16 mm; p = 0.010).
Neither of these differences exceeded the MCID and likewise were unlikely to be
clinically important. No complications, including surgical site infections, were
observed in either group. CONCLUSIONS: Periarticular analgesic injection for pain
control after THA did not result in a clinically important reduction in pain at
any point examined. Given the expense associated with this PAI mixture and the
lack of effectiveness outside this timeframe, we cannot recommend its use. Other
mixtures or concentrations of drugs may be helpful in short-stay admissions for
THA, but this will require further research. LEVEL OF EVIDENCE: Level I,
therapeutic study.
PMID- 29939896
TI - CORR Insights(r): Has Self-reported Marijuana Use Changed in Patients Undergoing
Total Joint Arthroplasty After the Legalization of Marijuana?
PMID- 29939895
TI - Intravenous Tranexamic Acid Reduces Postoperative Blood Loss After High Tibial
Osteotomy.
AB - BACKGROUND: Medial opening wedge high tibial osteotomy (HTO) entails extensive
soft tissue release that may lead to substantial perioperative bleeding. Although
tranexamic acid (TXA) is a well-established blood-conserving agent in total joint
arthroplasty, its potential to reduce blood loss in patients undergoing HTO has
not been studied extensively. QUESTIONS/PURPOSES: (1) Does TXA reduce total
estimated blood loss in HTO? (2) Does TXA use in HTO affect in-hospital endpoints
as measured by visual analog scale (VAS) pain scores at rest the day after
surgery, wound complications in the immediate postoperative period, blood
transfusions, or symptomatic deep vein thrombosis? METHODS: Between January 2015
and May 2017, a single surgeon performed 156 HTOs, all of which were done using
the medial opening wedge technique. We began using intravenous TXA for all HTOs
in June 2016. This left us with 89 patients who were treated during a time when
no TXA was used and 67 patients who were treated when all patients received TXA.
Two patients in the control group had simultaneous TKA in the contralateral leg
and one patient in each group had missing data so these patients were excluded,
leaving 86 (97%) patients in the control group and 66 (98.5%) in the TXA group
available for analysis in this retrospective study. There were no demographic
differences between the groups in terms of age, sex, body mass index, and
baseline hemoglobin values. Total estimated blood loss was the primary outcome
variable, which was calculated using total blood volume and decrease in
hemoglobin values. Secondary outcome variables included pain VAS at rest the day
after surgery, wound complications in the immediate postoperative period,
allogeneic blood transfusions, and occurrence of symptomatic thromboembolic
manifestations. The decision on when to transfuse was based on predetermined
criteria. An orthopaedic surgeon not involved in patient care collected the
patient data from electronic medical records and did chart review. RESULTS: The
TXA group had less total blood loss (372 +/- 36 mL versus 635 +/- 53 mL, mean
difference 263 mL [95% confidence interval, 248-278]; p < 0.001). Between groups,
differences in VAS pain scores at rest the day after surgery favored the TXA
group but were small and unlikely to be clinically important. There were two
wound complications in the control group (one hematoma and one superficial wound
infection) and none in the TXA group. No patients in either group received a
blood transfusion, and no symptomatic thromboembolic events were detected in
either group. CONCLUSIONS: This study demonstrates that the systemic
administration of TXA reduces postoperative blood loss in medial opening wedge
HTO; however, insofar as no transfusions were administered to patients even
before the routine use of TXA in this series, and no clinically important
differences in pain scores were identified, the clinical benefit of routine use
of TXA in patients undergoing HTO is uncertain. Our study was too small to make
safety-related claims on rare endpoints such as wound complications or
thromboembolic events. Larger, and preferably randomized, trials are needed to
help define whether it is important to use TXA in this setting. Our data can help
inform sample size calculations for such studies. LEVEL OF EVIDENCE: Level III,
therapeutic study.
PMID- 29939897
TI - Effects of Pre-race Apneas on 400-m Freestyle Swimming Performance.
AB - Robertson, C, Lodin-Sundstrom, A, O'Hara, J, King, R, Wainwright, B, and Barlow,
M. Effects of pre-race apneas on 400-m freestyle swimming performance. J Strength
Cond Res XX(X): 000-000, 2018-This study aimed to establish whether a series of 3
apneas before a 400-m freestyle time-trial affected swimming performance when
compared with and combined with a warm-up. Nine (6 males and 3 females) regional
to national standard swimmers completed four 400-m freestyle time-trials in 4
randomized conditions: without warm-up or apneas (CON), warm-up only (WU), apneas
only (AP), and warm-up and apneas (WUAP). Time-trial performance was
significantly improved after WUAP (275.79 +/- 12.88 seconds) compared with CON
(278.66 +/- 13.31 seconds, p = 0.035) and AP (278.64 +/- 4.10 seconds, p =
0.015). However, there were no significant differences between the WU (276.01 +/-
13.52 seconds, p > 0.05) and other interventions. Spleen volume compared with
baseline was significantly reduced after the apneas by a maximum of ~45% in the
WUAP and by ~20% in WU. This study showed that the combination of a warm-up with
apneas could significantly improve 400-m freestyle swim performance compared with
a control and apnea intervention. Further investigation into whether long-term
apnea training can enhance this response is justified.
PMID- 29939898
TI - Differences in Maturity, Morphological, and Fitness Attributes Between the Better
and Lower-Ranked Male and Female U-14 Portuguese Elite Regional Basketball
Teams.
AB - Ramos, S, Volossovitch, A, Ferreira, AP, Barrigas, C, Fragoso, I, and Massuca, L.
Differences in maturity, morphological and fitness attributes between the better-
and lower-ranked male and female U-14 Portuguese elite regional basketball teams.
J Strength Cond Res XX(X): 000-000, 2018-During a national championship, the
anthropometric, physiological, and maturation attributes of 13-14-year-old
players of regional selection basketball teams and their association with team's
final classification were analyzed. Body parameters (weight, height, skinfolds,
and lengths) were measured and physiological capacities assessed by sprint (20
m), agility, jump, and upper-body strength tests. Chronological age, maturity
offset (years from age at peak height velocity; YAPHV), and predicted age at peak
height velocity were calculated. In both sexes, no significant differences were
found for maturity. Anthropometric and physiological analysis indicated that male
players from finalist's teams were significantly faster, were more agile, threw
the medicine ball longer, and showed lower percentages of body fat than players
from lower-ranked teams. Further, semifinalists were faster than lower-ranked
players. In the same sense, female players from semifinalist teams demonstrated
to be significantly faster, more agile, and threw the medicine ball longer than
female players from lower-ranked teams. In addition, discriminant analysis showed
that speed (in boys) and the combination of speed and upper limb strength (in
girls) could successfully discriminate players with different performances in a
championship. In conclusion, speed and upper limb strength appear to be the
physical attributes associated with better team performance in youth basketball.
Coaches should be aware of the relationship between the improvement of these
physical attributes and the teaching-learning process of the basketball game.
PMID- 29939899
TI - Identification of Maximal Running Intensities During Elite Hurling Match-Play.
AB - Young, D, Malone, S, Beato, M, Mourot, L, and Coratella, G. Iidentification of
maximal running intensities during elite hurling match-play. J Strength Cond Res
XX(X): 000-000, 2018-The current study aimed to describe the duration-specific
running intensities of elite hurling players during competition with respect to
position using a rolling average method. Global positioning systems (10-Hz Viper;
STATSport, Viper, Newry, Northern Ireland) were used to collect data from 36
elite hurling players across 2 seasons. Players were categorized according to
playing positions (full-backs, half-backs, midfielders, half-forwards, and full
forwards). A total of 230 full match samples were obtained from 22 competitive
games for analysis. The velocity-time curve was analyzed using a rolling average
method, in which the maximum relative total distance (TD; m.min), high-speed
running distance (HSR; m.min), and sprint distance (SD; m.min) intensities were
calculated across 10 different rolling time durations (1-10 minutes) within each
game. There were large to very large (effect sizes [ES] = 0.66-4.33) differences
between 1 minute rolling averages and all other durations for TD, HSR, and SD.
However, pairwise comparisons between 6 and 10 minutes for TD, HSR, and SD were
smaller and more variable (ES = 0.07, trivial to ES = 0.85, moderate). Half
backs, midfielders, and half-forwards achieved a higher maximal relative TD and
HSR in all duration-specific fields when compared with full-backs and full
forwards. No positional difference was observed in 1- and 2-minute durations for
SD. Because the rolling average duration increased the maximum TD, HSR and SD
running intensities decreased across all positions. These data provide knowledge
of the peak running intensities of elite hurling competition and can be used to
design training activities to sufficiently prepare players for these "worst-case
scenarios."
PMID- 29939900
TI - High-Intensity Interval vs. Continuous Endurance Training: Preventive Effects on
Hormonal Changes and Physiological Adaptations in Prediabetes Patients.
AB - Safarimosavi, S, Mohebbi, H, and Rohani, H. High-intensity interval vs.
continuous endurance training: Preventive effects on hormonal changes and
physiological adaptations in prediabetes patients. J Strength Cond Res XX(X): 000
000, 2018-The aim of this study was to examine the effects of a 12-week high
intensity interval training (HIIT) intervention, or an isocaloric continuous
endurance training (CET) intervention on insulin resistance indices and change in
irisin and preptin in patients with prediabetes. Thirty-two prediabetic male
patients (age = 38.7 +/- 4; body mass index = 26.9 +/- 1.4 kg.m; and V[Combining
Dot Above]O2peak = 2.49 +/- 0.22 L.min) were randomly assigned into 3 training
groups (N = 8). These groups were matched based on the required energy
expenditure (EE) for completing each protocol: (a) HIIT (10 * 60 seconds at 90%
peak oxygen uptake [V[Combining Dot Above]O2peak], 1: 1 work to recovery at 50
W), (b) CET at an intensity equivalent to maximal fat oxidation (Fatmax) (CETFAT)
(pedaling for a duration that expends an equivalent EE to an HIIT session [E ~
HIIT]), (c) CET at an intensity equivalent to anaerobic threshold (CETAT) (E ~
HIIT), and (d) the control group (CON): continued to perform their daily
activities. After intervention, blood glucose levels were significantly (p <
0.05) lower in the HIIT group compared with CETAT group. Exercise training
improved the insulin resistance index by 35, 28, and 37% in CETFAT, CETAT, and
HIIT groups, respectively. Irisin concentrations in the HIIT and CETAT groups was
significantly (p < 0.05) decreased compared with the pre-training values. Also,
HIIT and CETFAT resulted in significant (p < 0.05) changes in preptin
concentration compared with baseline. This study demonstrated that both HIIT and
CETFAT protocols had similar effects on the insulin resistance index of
prediabetic patients. Also, the intensity and type of exercise were effective
factors in changing irisin and preptin concentrations.
PMID- 29939901
TI - Characterization of Heart Rate Responses, Duration, and Distances Traveled in
Youth Participating in Recreational Skateboarding at Community Skateparks.
AB - Furr, HN, Nessler, JA, and Newcomer, SC. Characterization of heart rate
responses, duration, and distances traveled in youth participating in
recreational skateboarding at community skateparks. J Strength Cond Res XX(X):
000-000, 2018-Recreational skateboarding continues to gain popularity in youth
within the United States and abroad. Surprisingly, there is a paucity of research
regarding the cardiovascular responses of youth participating in recreational
skateboarding. Therefore, the purpose of this study was to test the hypothesis
that skateboarding would elicit heart rates and durations consistent with the
American College of Sports Medicine (ACSM) and Center for Disease Control and
Prevention (CDC) recommendations for cardiovascular fitness in youth. Seventy-one
recreational skateboarders (boys: 63 and girls: 8) between the ages of 6 and 17
years participated in this study. Data were acquired at 9 skateparks in the local
community. After parental consent, participants completed a questionnaire and
were instrumented with a heart rate monitor (Polar V800 GPS Sports Watch), which
recorded heart rate, duration, and distance traveled. Participants were
instructed to engage in typical skateboarding activities, with the duration and
intensity of activity determined by the individual. Participants were 10.6 +/-
2.9 years old and had participated in skateboarding for 3.1 +/- 2.4 years. On
average, subjects skateboarded 55.5 +/- 28.4 minutes, at an average heart rate of
140.4 +/- 16.1 b.min, and traveled an average distance of 2.65 +/- 1.87 km.
Results from this study suggest that youth participating in recreational
skateboarding at community skateparks attain exercise intensities and durations
that are comparable with the ACSM's and CDC's exercise recommendations for
cardiovascular fitness in youth. These findings may hold implications for city
planners considering the impact of community skateparks on physical activity in
youth and overall public health.
PMID- 29939902
TI - Validity of Heart Rate-Based Models for Estimating Oxygen Uptake During Tennis
Play.
AB - Baiget, E, Iglesias, X, and Rodriguez, FA. Validity of heart rate-based models
for estimating oxygen uptake during tennis play. J Strength Cond Res XX(X): 000
000, 2018-This study aimed to assess the validity of an on-court tennis test
(specific endurance tennis test [SET-Test]) and 2 heart rate (HR)-based methods
for estimating oxygen uptake (V[Combining Dot Above]O2) in competitive tennis
players. Thirty-five male players performed a SET-Test to relate test duration
(minutes) and V[Combining Dot Above]O2. Two weeks later, 16 players performed a
simulated match play set where HR and V[Combining Dot Above]O2 (V[Combining Dot
Above]O2-PLAY, criterion value) were measured and then compared with V[Combining
Dot Above]O2 values predicted from the HR/V[Combining Dot Above]O2 linear
regression equations derived from the SET-Test (pV[Combining Dot Above]O2-TEST)
and from the one set match play (pV[Combining Dot Above]O2-PLAY). Test duration
and V[Combining Dot Above]O2-TEST were strongly correlated (r = 0.821, p < 0.001,
SEE = 5.6 ml.kg.min), indicating that SET-Test outcome is a somewhat good
indicator of aerobic fitness in tennis players, likely to be useful for training
purposes. pV[Combining Dot Above]O2-PLAY and V[Combining Dot Above]O2-PLAY
(criterion value) were strongly correlated (r = 0.832, p < 0.001) and SEE was
moderate (3.5 ml.kg.min = 11.5%). pV[Combining Dot Above]O2-TEST differed from
the criterion (32.4 +/- 10.7 vs. 30.8 +/- 8.6 ml.kg.min, p < 0.001) and, although
strongly correlated (r = 0.689, p < 0.001), an overestimation occurred (mean
Delta = 1.6 ml.kg.min = 4.9%), yielding a high SEE (4.8 ml.kg.min = 15.6%). We
conclude that (a) SET-Test performance is a valid and moderately accurate
predictor of V[Combining Dot Above]O2; and (b) the individual HR-V[Combining Dot
Above]O2 regression equation generated during tennis match play predicts
V[Combining Dot Above]O2 with greater accuracy than the regression derived from
the SET-Test.
PMID- 29939903
TI - Reliability, Sensitivity, and Minimal Detectable Change of a New Specific
Climbing Test for Assessing Asymmetry in Reach Technique.
AB - Cular, D, Dhahbi, W, Kolak, I, Iacono, AD, Beslija, T, Laffaye, G, and Padulo, J.
Reliability, sensitivity, and minimal detectable change of a new specific
climbing test for assessing asymmetry in reach technique. J Strength Cond Res
XX(X): 000-000, 2018-The aims of this study were to establish intertrial and
intersession reliability, sensitivity, and minimal detectable change of a new
climbing test specifically for assessing asymmetry in reach technique (TEST).
Twenty-four young climbers (16 males and 8 females) participated in this study.
The protocol consisted of performing, in counterbalanced random order, 3 tests;
TEST, maximum handgrip force, and squat on the bench, in 2 sessions (with 3
trials for each session). TEST performance was expressed as: TEST performance for
left hand (TESTL), TEST performance for right hand (TESTR), and absolute symmetry
index (ASI). For intertrial and intersession reliability assessment, TESTL and
TESTR showed excellent reliability (intraclass correlation coefficients ranged:
0.96-1.00; SEM% ranged: 0.07-1.23; and coefficient of variation-CV%: 1.28-2.53).
In addition, SEMs were smaller than the smallest worthwhile change (SWC) values
(SWC% = 1.07 and 0.99 for TESTL and TESTR, respectively), and the minimal
detectable change (MDC95) for both sides was small (<4.36 cm). An exception was
ASI, which showed low absolute reliability and marginal sensitivity (SEM% = 15.13
> SWC% = 8.40 and CV% = 41.98). Pairwise test comparisons revealed no difference
between sides. Considering the high reliability and the satisfactory sensitivity,
TEST can be used to define individual asymmetry in the performance of the reach
technique to the left or the right body side in climbers. However, interpreting
data using the ASI index requires caution because it had poor absolute
reliability and marginal sensitivity.
PMID- 29939904
TI - Influence of Reactive and Maximum Strength Indicators on Sprint Performance.
AB - Healy, R, Smyth, C, Kenny, IC, and Harrison, AJ. Influence of reactive and
maximum strength indicators on sprint performance. J Strength Cond Res XX(X): 000
000, 2018-The primary aim of this study was to assess the relationship between
reactive and maximal strength measures with 40 m sprint performance and
mechanical properties. Fourteen male and 14 female sprinters participated in this
study. On the first day, subjects performed 40 m sprints with 10-m split times
recorded in addition to maximal theoretical velocity, maximal theoretical force
and peak horizontal power, which were calculated from force-velocity
relationships. On the second day, subjects performed isometric midthigh pulls
(IMTPs) with peak force (PF) and relative PF calculated, drop jumps (DJs) and
vertical hopping where the reactive strength index (RSI) was calculated as jump
height (JH) divided by contact time (CT). Pearson correlations were used to
assess the relationships between measures and independent samples t-tests were
used to assess the differences between men and women. No significant correlations
were found between DJ and hopping RSI and sprint measures. A significant strong
positive correlation was found between IMTP PF and peak horizontal power in men
only (r = 0.61). The male sprinters performed significantly better in all
recorded measures apart from hopping (CT, JH and RSI) and DJ CT where no
significant differences were found. The lack of association between reactive and
maximal strength measures with sprint performance is potentially because of the
test's prolonged CTs relative to sprinting and the inability to assess the
technical application of force. Several methods of assessing reactive strength
are needed that can better represent the demands of the distinct phases of
sprinting e.g., acceleration, maximum velocity.
PMID- 29939905
TI - Risk Factors and Number of Falls as Determinants of Quality of Life of Community
Dwelling Older Adults.
AB - BACKGROUND AND PURPOSE: In older adults, the psychological impact and effects
related to the loss of functional capacity are directly related to perceived
quality of life (QOL). The predictors of better QOL are increased physical
activity, lower prevalence of overweight, lower cases of depression, and lower
rate of reported alcohol abuse. On the contrary, the predictors of decreased QOL
are female gender, comorbidity, deficient nutritional condition, polypharmacy,
loss of mobility, depression and dependency, poor economic conditions, and social
isolation and loneliness. Furthermore, QOL in older adults is more dependent on
the number of falls than comorbidity. The objective was to investigate the
determinants of perceived QOL among independent community-dwelling older adults
and to quantify the influence of number of falls and number of risk factors on
QOL. METHODS: This is a cross-sectional study of 572 older adults (>70 years of
age) seen in 10 primary care centers in La Ribera, Valencia, Spain. Comprehensive
geriatric assessment was done by 4 nurses in primary care centers. Functional
status and sociodemographic and clinical variables were collected. Quality of
life was assessed by EQ-5D scale. RESULTS: Females predominated (63.3%). Mean age
(standard deviation) was 76.1 (3.9) years. The male gender (beta= .09; 95%
confidence interval [CI]: 0.05-0.13) was found to be predictive of better QOL,
together with physical activity (beta= .04; 95% CI: 0.02-0.06), while the use of
drugs affecting the central nervous system (beta=-.08; 95% CI: -0.12 to -0.03),
overweight (beta=-.06; 95% CI: 0.1 to - 0.02), comorbidity (beta=-.09; 95% CI:
0.13 to -0.05), the presence of fall risk factors (beta=-.02; 95% CI: -0.03 to
0.01), and the number of previous falls (beta=-.03; 95% CI: -0.06 to 0.01) had a
negative impact upon the EQ-5D Index score. CONCLUSIONS: If perceived QOL is used
as an indicator of the success of intervention programs, certain factors
accompanying the adoption of measures for the prevention of falls may mask the
results (failure or success) of the intervention. Because most determinants of
QOL are modifiable and physical activity has the potential to improve QOL, this
research suggests that physical activity programs should be a component of health
care for older adults.
PMID- 29939906
TI - Cerulein-Induced Acute Pancreatitis Affects Sphingomyelin Signaling Pathway in
Rats.
AB - OBJECTIVES: Acute pancreatitis (AP) is a common and severe gastrointestinal
inflammatory disease with poorly understood pathogenesis. We adopted cerulein
induced pancreatitis, a well-established rat model shearing similarities with
human AP, to determine the disease background. Special interest was placed on
sphingolipids, because their signaling pathways are involved in many pathological
states including hepatic steatosis, heart infarction, or pancreatic origin type 1
diabetes. METHODS: Sphingolipid levels in the blood and pancreas were determined
by the means of chromatography (thin-layer and high-performance liquid
chromatography). RESULTS: We found that AP leads to activation of ceramide de
novo synthesis pathway, as evidenced by a significant increment in sphinganine,
that is, ceramide synthesis precursor, content (+3.8-fold). Surprisingly, despite
the reported growth in sphinganine concentration, we observed a reduced (-38%)
ceramide level in the pancreas of rats with AP. The results could be explained by
subsequent hydrolysis of ceramide to other secondary messengers, that is,
sphingosine (+4-fold) or sphingosine-1-phosphate (+3-fold). CONCLUSIONS: Because
it is known that sphingosine-1-phosphate and some of its analogs could have a
protective role against AP complications, our findings may contribute to
elaboration of new therapeutic strategies in the management of this severe
medical condition.
PMID- 29939907
TI - Association Between Opioid Use and Survival Time in Patients With Unresectable
Pancreatic Cancer: 10 Years of Clinical Experience.
AB - OBJECTIVES: Patients with pancreatic cancer generally experience increasing pain
as their disease progresses, making the titration of opioids difficult. This
study aimed to determine a correlation between prescribed opioid doses and
survival time in patients with unresectable pancreatic cancer. METHODS: This
retrospective observational cohort study in a tertiary care institution reviewed
the medical records of patients diagnosed with unresectable pancreatic cancer and
treated over a 10-year period. RESULTS: We screened 1152 patients with
unresectable pancreatic cancer, and 566 were eligible for inclusion in this
study. There was a statistically significant negative correlation between initial
opioid dose and survival time from initial opioid dose (correlation coefficient,
0.184; P < 0.01) and survival time from initial pancreatic cancer diagnosis
(correlation coefficient, -0.177; P < 0.01). In addition, there were 0.8% and
0.6% increases in initial opioid dosage (morphine equivalent daily dose) and rate
of increasing opioid dose (morphine equivalent daily dose per month),
respectively, associated with the risk of early death (<=180 days, P < 0.05).
CONCLUSIONS: Correlations between patient survival, initial opioid dose, final
opioid dose, and the rate of increase of opioid dosage could provide useful
information for clinicians treating unresectable pancreatic cancer patients.
PMID- 29939908
TI - Association Between Hepatitis B Infection and Pancreatic Cancer: A Population
Based Analysis in the United States.
AB - OBJECTIVES: The aim of this study was to assess the role of hepatitis B (HepB)
infection in the causation of pancreatic cancer and the predictors of pancreatic
cancer and mortality. METHODS: We identified pancreatic cancer patients 11 to 70
years of age from the 2013-2014 National Inpatient Sample. Pearson chi test and
Student's t-test were used for categorical and continuous variables,
respectively. We assessed the association of HepB and pancreatic cancer and the
independent mortality predictors by multivariate analyses. RESULTS: Of 69,210
pancreatic cancer patients, 175 patients with a history of HepB and 69,035
patients without a history of HepB were identified. Compared with the pancreatic
cancer-non-HepB group, the pancreatic cancer-HepB group consisted more of younger
(mean, 60.4 [standard deviation, 7.4] years vs 68.2 [standard deviation, 12.1]
years), male, black, and Asian patients with low household income and nonelective
admissions. The odds of developing pancreatic cancer among the HepB patients were
significantly higher (adjusted odds ratio, 1.24; 95% confidence interval, 1.056
1.449; P = 0.008). Black race, age >= 65 years, and male sex demonstrated greater
odds of mortality. CONCLUSIONS: This study concluded up to a 24% increased
likelihood of pancreatic cancer among the HepB patients. Blacks showed greater
odds of pancreatic cancer and related mortality.
PMID- 29939909
TI - Plasma Neurokinin A Levels Predict Survival in Well-Differentiated Neuroendocrine
Tumors of the Small Bowel.
AB - OBJECTIVES: Elevated neurokinin A (NKA) levels are associated with poor prognosis
in patients with small bowel neuroendocrine tumors. We hypothesized that patients
with NKA levels that remain elevated despite treatment with surgical
cytoreduction have a poor prognosis. METHODS: Patients diagnosed with small bowel
neuroendocrine tumors who underwent surgical cytoreduction at our institution
were identified. Demographics, histopathologic characteristics, and biochemical
data were collected. Patients were grouped by the trend of their NKA levels
(group 1, continuously normal; group 2, transiently elevated but normalized after
therapy; group 3, remained elevated despite therapy). Survival rates were
calculated from the date of the patient's first NKA level. RESULTS: Serial NKA
values after surgical cytoreduction were monitored in 267 patients. Kaplan-Meier
2-year, 5-year, and 10-year survival rates were as follows: group 1 (n = 157),
97%, 89%, and 62%; group 2 (n = 78), 99%, 90%, and 78%; and group 3 (n = 32),
88%, 69%, and 0%. Survival rates were statistically significant between groups 1
and 3 and between groups 2 and 3 (P < 0.01). CONCLUSIONS: Serial monitoring of
plasma NKA levels is useful in identifying patients who have a poor prognosis.
Elevated NKA levels can indicate the need for immediate therapeutic intervention.
PMID- 29939910
TI - Quality-adjusted Life Years (QALY) for 15 Chronic Conditions and Combinations of
Conditions Among US Adults Aged 65 and Older.
AB - BACKGROUND: Although the life expectancy for the US population has increased, a
high proportion of this population has lived with >=1 chronic conditions. We have
quantified the burden of disease associated with 15 chronic conditions and
combinations of conditions by estimating quality-adjusted life years (QALYs) for
older US adults. RESEARCH DESIGN: Data were from the Medicare Health Outcomes
Survey Cohort 15 (baseline survey in 2012, follow-up survey 2014, with mortality
follow-up through January 31, 2015). We included individuals aged 65 years and
older (n=96,481). We estimated mean QALY throughout the remainder of the lifetime
according to the occurrence of these conditions. RESULTS: The age-adjusted QALY
was 5.8 years for men and 7.8 years for women. Over 90% respondents reported at
least 1 condition and 72% reported multiple conditions. Respondents with
depression and congestive heart failure had the lowest age-adjusted QALY (1.1-1.5
y for men and 1.5-2.2 y for women), whereas those with hypertension, arthritis,
and sciatica had higher QALY (4.2-5.4 and 6.4-7.2 y, respectively). Having either
depression or congestive heart failure and any 1 or 2 of the other 13 conditions
was associated with the lowest QALY among the possible dyads and triads of
chronic conditions. Dyads and triads with hypertension or arthritis were more
prevalent, but had higher QALY. CONCLUSIONS: Understanding the burden of disease
for common chronic conditions and for combinations of these conditions is useful
for delivering high-quality primary care that could be tailored for individuals
with combinations of chronic conditions.
PMID- 29939911
TI - Associations of CAHPS Composites With Global Ratings of the Doctor Vary by
Medicare Beneficiaries' Health Status.
AB - RESEARCH OBJECTIVE: Care coordination among health care providers is essential
for high-quality care and it is strongly associated with overall ratings of
doctors. Care coordination may be especially important for sicker and chronically
ill patients because of the multiple providers involved in their care. This study
examines whether the association of care coordination with global ratings of
one's personal doctor varies by number of chronic conditions and self-rated
health. STUDY DESIGN: We used nationally representative Medicare Consumer
Assessment of Healthcare Providers and Systems (CAHPS) survey data to evaluate
care coordination, doctor communication, getting needed care, getting care
quickly, count of 6 chronic conditions (angina, cancer, chronic obstructive
pulmonary disease, diabetes, heart attack, stroke), self-rated general health (5
point scale, poor to excellent, scored linearly), and interactions among them as
predictors of the CAHPS global rating of personal doctor (scored 0-100 with 100
being best possible personal doctor) using linear regression models. The analytic
sample included 242,871 Medicare fee-for-service and managed care beneficiaries
in 2013: 56% female; 14% 18-64, 47% 65-74, 27% 75-84, and 11% 85 and older; and
48% high school education or less. RESULTS: The CAHPS composites (of care
coordination, doctor communication, getting needed care, and getting care
quickly) and number of chronic conditions were significantly positively
associated with ratings of personal doctor (P<0.05). Care coordination and doctor
communication had a stronger association with positive ratings of the personal
doctor among those with worse self-rated health (P<0.001). DISCUSSION: Results
were consistent with the hypothesis that patients in worse health weigh care
coordination more heavily in global physician assessments than patients in better
health. Emphasis on improving care coordination, especially for patients in
poorer health, may improve patients' overall assessments of their providers. The
study provides further evidence for the importance of care coordination
experiences in the era of patient-centered care.
PMID- 29939912
TI - Why Effective Interventions Do Not Work for All Patients: Exploring Variation in
Response to a Chronic Disease Management Intervention.
AB - BACKGROUND: Half of all Americans have a chronic disease. Promoting healthy
behaviors to decrease this burden is a national priority. A number of behavioral
interventions have proven efficacy; yet even the most effective of these has high
levels of nonresponse. OBJECTIVES: In this study, we explore variation in
response to an evidence-based community health worker (CHW) intervention for
chronic disease management. RESEARCH DESIGN: We used a convergent parallel design
that combined a randomized controlled trial with a qualitative process evaluation
that triangulated chart abstraction, in-depth interviews and participant
observation. SUBJECTS: Eligible patients lived in a high-poverty region and were
diagnosed with 2 or more of the following chronic diseases: diabetes, obesity,
hypertension or tobacco dependence. There were 302 patients in the trial, 150 of
whom were randomly assigned to the CHW intervention. Twenty patients and their
CHWs were included in the qualitative evaluation. RESULTS: We found minimal
differences between responders and nonresponders by sociodemographic or clinical
characteristics. A qualitative process evaluation revealed that health behavior
change was challenging for all patients and most experienced failure (ie, gaining
weight or relapsing with cigarettes) along the way. Responders seemed to increase
their resolve after failed attempts at health behavior change, while
nonresponders became discouraged and "shut down." CONCLUSIONS: Failure is a
common and consequential aspect of health behavior change; a deeper understanding
of failure should inform chronic disease interventions.
PMID- 29939914
TI - Sexual Assault and Women's Health: Universal Screening or Universal Precautions?
PMID- 29939913
TI - Which Readmissions May Be Preventable? Lessons Learned From a Posthospitalization
Care Transitions Program for High-risk Elders.
AB - BACKGROUND: Care transitions programs have been shown to reduce hospital
readmissions. OBJECTIVES: The main objective of this study was to evaluate
effects of the Mayo Clinic Care Transitions (MCCTs) Program on potentially
preventable and nonpreventable 30-day unplanned readmissions among high-risk
elders. RESEARCH DESIGN: This was a retrospective cohort study of patients
enrolled in MCCT following hospitalization and propensity score-matched controls
receiving usual primary care. SUBJECTS: The subjects were primary care patients,
who were 60 years or older, at high-risk for readmission, and hospitalized for
any cause between January 1, 2011 and June 30, 2013. MEASURES: Hospital
readmission within 30 days. The 3M algorithm was used to identify potentially
preventable readmissions. Readmissions for ambulatory care sensitive conditions,
a subset of preventable readmissions identified by the 3M algorithm, were also
assessed. RESULTS: The study cohort included 365 pairs of MCCT enrollees and
propensity score-matched controls. Patients were similar in age (mean 83 y) and
other baseline demographic and clinical characteristics, including reason for
index hospitalization. MCCT enrollees had a significantly lower all-cause
readmission rate [12.4% (95% confidence interval: CI, 8.9-15.7) vs. 20.1% (15.8
24.1); P=0.004] resulting from a decrease in potentially preventable readmissions
[8.4% (95% CI, 5.5-11.3) vs. 14.3% (95% CI, 10.5-17.9); P=0.01]. Few potentially
preventable readmissions were for ambulatory care sensitive conditions (6.7% vs.
12.0%). The rates of nonpotentially preventable readmissions were similar [4.3%
(95% CI, 2.2-6.5) vs. 6.7% (95% CI, 4.0-9.4); P=0.16]. Potentially preventable
readmissions were reduced by 44% (hazard ratio, 0.56; 95% CI, 0.36-0.88; P=0.01)
with no change in other readmissions. CONCLUSIONS: The MCCT significantly reduces
preventable readmissions, suggesting that access to multidisciplinary care can
reduce readmissions and improve outcomes for high-risk elders.
PMID- 29939915
TI - Ulipristal Acetate for Treatment of Symptomatic Uterine Leiomyomas: A Randomized
Controlled Trial.
PMID- 29939916
TI - In Reply.
PMID- 29939917
TI - Clinical Factors Associated With Presentation Change of the Second Twin After
Vaginal Delivery of the First Twin.
PMID- 29939918
TI - In Reply.
PMID- 29939919
TI - Abnormal Vaginal Bleeding in Women Desiring Contraception Who Are Taking
Anticoagulation Therapy.
PMID- 29939920
TI - In Reply.
PMID- 29939921
TI - Manual Compared With Electric Vacuum Aspiration for Treatment of Molar Pregnancy.
PMID- 29939923
TI - Racial Disparities in Surgical Outcomes During Peripartum Hysterectomy [26J]:
Correction.
PMID- 29939922
TI - In Reply.
PMID- 29939925
TI - Simultaneous Compared With Interval Medical Abortion Regimens Where Home Use Is
Restricted: Correction.
PMID- 29939924
TI - Patient Race/Ethnicity Are Predictors for Peripartum Hysterectomy [27J]:
Correction.
PMID- 29939926
TI - Clinical Factors Associated With Presentation Change of the Second Twin After
Vaginal Delivery of the First Twin: Correction.
PMID- 29939927
TI - Limbo: Correction.
PMID- 29939928
TI - Notice of Retraction: "Sentinel Lymph Node Mapping in Endometrioid Endometrial
Cancer: Does It Work in the Real World? [22A]" (Valieva O, Greer DM, Kram JJF,
Schmit E, Dickson E, Kamelle SA).
PMID- 29939932
TI - ACOG Publications.
PMID- 29939933
TI - ACOG Practice Bulletin No. 196 Summary: Thromboembolism in Pregnancy.
AB - Women who are pregnant or in the postpartum period have a fourfold to fivefold
increased risk of thromboembolism compared with nonpregnant women (1, 2).
Approximately 80% of thromboembolic events in pregnancy are venous (3), with a
prevalence of 0.5-2.0 per 1,000 pregnant women (4-9). Venous thromboembolism
(VTE) is one of the leading causes of maternal mortality in the United States,
accounting for 9.3% of all maternal deaths (10).The prevalence and severity of
this condition during pregnancy and the peripartum period warrant special
consideration of management and therapy. Such therapy includes the treatment of
acute thrombotic events and prophylaxis for those at increased risk of thrombotic
events. The purpose of this document is to provide information regarding the risk
factors, diagnosis, management, and prevention of thromboembolism, particularly
VTE in pregnancy. This Practice Bulletin has been revised to reflect updated
guidance regarding screening for thromboembolism risk and management of
anticoagulation around the time of delivery.
PMID- 29939934
TI - ACOG Practice Bulletin No. 197 Summary: Inherited Thrombophilias in Pregnancy.
AB - Inherited thrombophilias are associated with an increased risk of venous
thromboembolism and have been linked to adverse outcomes in pregnancy. However,
there is limited evidence to guide screening for and management of these
conditions in pregnancy. The purpose of this document is to review common
thrombophilias and their association with maternal venous thromboembolism risk
and adverse pregnancy outcomes, indications for screening to detect these
conditions, and management options in pregnancy. This Practice Bulletin has been
revised to provide additional information on recommendations for candidates for
thrombophilia evaluation, updated consensus guidelines regarding the need for
prophylaxis in women with an inherited thrombophilia during pregnancy and the
postpartum period, and discussion of new published consensus guidelines from the
Society for Obstetric Anesthesia and Perinatology addressing thromboprophylaxis
and neuraxial anesthetic considerations in the obstetric population.
PMID- 29939935
TI - ACOG Committee Opinion No. 742 Summary: Postpartum Pain Management.
AB - Pain and fatigue are the most common problems reported by women in the early
postpartum period. Pain can interfere with a woman's ability to care for herself
and her infant. Untreated pain is associated with a risk of greater opioid use,
postpartum depression, and development of persistent pain. Nonpharmacologic and
pharmacologic therapies are important components of postpartum pain management.
Because 81% of women in the United States initiate breastfeeding during the
postpartum period, it is important to consider the drug effects of all prescribed
medications on the mother-infant dyad. Multimodal analgesia uses drugs that have
different mechanisms of action, which potentiates the analgesic effect. If
opioids are included, a multimodal regimen used in a stepwise approach allows for
administration of lower doses of opioids. Given interindividual variation in
metabolism of opioids, as well as the risk of maternal and neonatal adverse
effects in women who are ultra-rapid metabolizers of codeine, monitoring for
excessive sedation and other adverse effects in infants is prudent for women who
are prescribed opiates. Although the U.S. Food and Drug Administration
recommendations underscore the need for anticipatory guidance regarding opioid
effects in all patients, obstetrician-gynecologists and other obstetric care
providers should ensure that the application of this guidance does not interfere
with pain control or disrupt breastfeeding during the postpartum period. Women
with opioid use disorder, women who have chronic pain, and women who are using
other medications or substances that may increase sedation need additional
support in managing postpartum pain.
PMID- 29939936
TI - ACOG Committee Opinion No. 743 Summary: Low-Dose Aspirin Use During Pregnancy.
AB - Low-dose aspirin has been used during pregnancy, most commonly to prevent or
delay the onset of preeclampsia. The American College of Obstetricians and
Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending
daily low-dose aspirin beginning in the late first trimester for women with a
history of early-onset preeclampsia and preterm delivery at less than 34 0/7
weeks of gestation, or for women with more than one prior pregnancy complicated
by preeclampsia. The U.S. Preventive Services Task Force published a similar
guideline, although the list of indications for low-dose aspirin use was more
expansive. Daily low-dose aspirin use in pregnancy is considered safe and is
associated with a low likelihood of serious maternal, or fetal complications, or
both, related to use. The American College of Obstetricians and Gynecologists and
the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task
Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81
mg/day) prophylaxis is recommended in women at high risk of preeclampsia and
should be initiated between 12 weeks and 28 weeks of gestation (optimally before
16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should
be considered for women with more than one of several moderate risk factors for
preeclampsia. Women at risk of preeclampsia are defined based on the presence of
one or more high-risk factors (history of preeclampsia, multifetal gestation,
renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic
hypertension) or more than one of several moderate-risk factors (first pregnancy,
maternal age of 35 years or older, a body mass index greater than 30, family
history of preeclampsia, sociodemographic characteristics, and personal history
factors). In the absence of high risk factors for preeclampsia, current evidence
does not support the use of prophylactic low-dose aspirin for the prevention of
early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.
PMID- 29939937
TI - ACOG Clinical Updates Summary: Incidental Radiologic Findings: Primary and
Preventive Care Review.
AB - Over the past several decades, the use of cross-sectional imaging has steadily
increased largely because of increasing refinements in imaging technology. The
progressive improvement in both spatial and temporal resolution of imaging
modalities over the years has enabled radiologists to diagnose and characterize
disorders with increasing accuracy. However, improved resolution has led to the
increased detection of imaging findings that may or may not be clinically
relevant. Such incidental findings or "incidentalomas" may be difficult to
differentiate from clinically relevant lesions. Radiologists may provide
disparate recommendations regarding incidental or indeterminate findings when
interpreting results of gynecologic and obstetric imaging examinations in routine
clinical practice. Vague recommendations pose challenges for referring clinicians
who are unable to determine the clinical relevance of such lesions. Therefore, a
general awareness of incidental lesions for any given abdominal or thoracic organ
is important for obstetrician-gynecologists involved in the management of
patients who require imaging studies. The aim of this monograph is to aid
obstetrician-gynecologists in the detection, characterization, and management of
incidentally detected lesions that may be encountered on routine women's imaging
examinations.
PMID- 29939938
TI - ACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy.
AB - Women who are pregnant or in the postpartum period have a fourfold to fivefold
increased risk of thromboembolism compared with nonpregnant women ().
Approximately 80% of thromboembolic events in pregnancy are venous (), with a
prevalence of 0.5-2.0 per 1,000 pregnant women (). Venous thromboembolism (VTE)
is one of the leading causes of maternal mortality in the United States,
accounting for 9.3% of all maternal deaths ().The prevalence and severity of this
condition during pregnancy and the peripartum period warrant special
consideration of management and therapy. Such therapy includes the treatment of
acute thrombotic events and prophylaxis for those at increased risk of thrombotic
events. The purpose of this document is to provide information regarding the risk
factors, diagnosis, management, and prevention of thromboembolism, particularly
VTE in pregnancy. This Practice Bulletin has been revised to reflect updated
guidance regarding screening for thromboembolism risk and management of
anticoagulation around the time of delivery.
PMID- 29939939
TI - ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy.
AB - Inherited thrombophilias are associated with an increased risk of venous
thromboembolism and have been linked to adverse outcomes in pregnancy. However,
there is limited evidence to guide screening for and management of these
conditions in pregnancy. The purpose of this document is to review common
thrombophilias and their association with maternal venous thromboembolism risk
and adverse pregnancy outcomes, indications for screening to detect these
conditions, and management options in pregnancy. This Practice Bulletin has been
revised to provide additional information on recommendations for candidates for
thrombophilia evaluation, updated consensus guidelines regarding the need for
prophylaxis in women with an inherited thrombophilia during pregnancy and the
postpartum period, and discussion of new published consensus guidelines from the
Society for Obstetric Anesthesia and Perinatology addressing thromboprophylaxis
and neuraxial anesthetic considerations in the obstetric population.
PMID- 29939940
TI - ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy.
AB - Low-dose aspirin has been used during pregnancy, most commonly to prevent or
delay the onset of preeclampsia. The American College of Obstetricians and
Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending
daily low-dose aspirin beginning in the late first trimester for women with a
history of early-onset preeclampsia and preterm delivery at less than 34 0/7
weeks of gestation, or for women with more than one prior pregnancy complicated
by preeclampsia. The U.S. Preventive Services Task Force published a similar
guideline, although the list of indications for low-dose aspirin use was more
expansive. Daily low-dose aspirin use in pregnancy is considered safe and is
associated with a low likelihood of serious maternal, or fetal complications, or
both, related to use. The American College of Obstetricians and Gynecologists and
the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task
Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81
mg/day) prophylaxis is recommended in women at high risk of preeclampsia and
should be initiated between 12 weeks and 28 weeks of gestation (optimally before
16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should
be considered for women with more than one of several moderate risk factors for
preeclampsia. Women at risk of preeclampsia are defined based on the presence of
one or more high-risk factors (history of preeclampsia, multifetal gestation,
renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic
hypertension) or more than one of several moderate-risk factors (first pregnancy,
maternal age of 35 years or older, a body mass index greater than 30, family
history of preeclampsia, sociodemographic characteristics, and personal history
factors). In the absence of high risk factors for preeclampsia, current evidence
does not support the use of prophylactic low-dose aspirin for the prevention of
early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.
PMID- 29939941
TI - Novel IL2RG Mutation Causes Leaky TLOWB+NK+ SCID With Nodular Regenerative
Hyperplasia and Normal IL-15 STAT5 Phosphorylation.
AB - X-linked severe combined immunodeficiency disease (SCID) is caused by mutations
in the interleukin (IL)-2 receptor gamma (IL2RG) gene and patients usually
present with a TBNK SCID phenotype. Nevertheless, a minority of these patients
present with a TBNK phenotype, similar to the IL-7R-deficient patients. We report
a patient with a novel missense p.Glu297Gly mutation in the IL2RG gene presenting
with a leaky TBNK SCID with delayed onset, moderate susceptibility to infections,
and nodular regenerative hyperplasia. He presents with preserved STAT5 tyrosine
phosphorylation in response to IL-15 stimulation but not in response to IL-2 and
IL-7, resulting in the NK phenotype.
PMID- 29939942
TI - Home blood pressure variability and subclinical atherosclerosis in multiple
vascular beds: a population-based study.
AB - OBJECTIVE: The mechanism by which higher blood pressure (BP) variability causes
cardiovascular events remains unclear. Experimental results indicate that
alterations in vessel wall tension related to BP variability may initiate
atherosclerosis through oscillatory shear stress. We examined associations of
home BP variability with subclinical atherosclerosis at four anatomically
distinct vascular beds. METHODS: In a cross-sectional population-based study of
1033 Japanese (mean age, 64.0 years; men, 88.7%) without known cardiovascular
disease, we defined SBP and DBP variability as variability independent of the
mean (VIM) across self-measured home BP values during seven consecutive days and
quantified coronary and aortic artery calcification (CAC and AAC) by computed
tomography, carotid intima-media thickness (CIMT) by ultrasonography, and ankle
brachial index (ABI). RESULTS: In multivariable adjusted models including mean
SBP, higher VIM of SBP was associated with CIMT greater than1.0 mm [relative risk
(95% confidence interval) fourth versus first quartile, 1.71 (1.15-2.54)], AAC
score greater than 0 [1.08 (1.02-1.15)], and ABI less than 1.1 [1.49 (1.12
1.97)], and linear trends were also statistically significant. However, there was
no significant association between VIM of SBP and CAC score greater than 0.
Meanwhile, higher VIM of DBP was associated only with AAC score greater than 0.
The associations were similar when modeling subclinical atherosclerosis severity
as continuous outcomes and were consistent across subgroups based on
demographics, behavioural, and cardiovascular risk factors. CONCLUSION: Higher
variability in home BP, particularly in home SBP, was associated with greater
carotid, aortic, and peripheral but not coronary atherosclerosis burdens
independent of the mean home BP.
PMID- 29939943
TI - Comparison of the SphygmoCor XCEL device with applanation tonometry for pulse
wave velocity and central blood pressure assessment in youth.
AB - BACKGROUND: Vascular phenotype by assessing carotid-femoral pulse wave velocity
(cf-PWV) and central SBP (cSP) in the young could be used as an intermediate
cardiovascular outcome measure. Tonometry is considered the gold-standard
technique, but its use is challenging in clinical practice, especially when used
in children. The purpose of this study was to validate cf-PWV and cSP assessment
with novel oscillometric device (SphygmoCor XCEL) in children and adolescents.
METHODS: cf-PWV and cSP were measured in 72 children and adolescents aged 6-20
years. Measurements were performed by applanation tonometry and by the SphygmoCor
XCEL device at the same visit under standardized conditions. Regression analysis
and Bland-Altman plots were used for comparison of the tonometer-based with
oscillometric-based method. RESULTS: Mean cf-PWV measured by applanation
tonometry was 4.85 +/- 0.81 m/s and measured by SpygmoCor XCEL was 4.75 +/- 0.81
m/s. The mean difference between the two devices was 0.09 +/- 0.47 m/s (P = NS).
cSP measured by SpygmoCor XCEL was strongly correlated with cSP measured by
applanation tonometry (R = 0.87, P < 0.001). Mean cSP measured by applanation
tonometry was 103.23 +/- 9.43 mmHg and measured by SpygmoCor XCEL was 103.54 +/-
8.87 mmHg. The mean cSP difference between the two devices was -0.30 +/- 3.34
mmHg (P = NS), and fulfilled the AAMI criterion 1. The estimated intersubject
variability was 2.17 mmHg. CONCLUSION: The new oscillometric SphygmoCor XCEL
device provides equivalent results for cf-PWV and cSP values to those obtained by
tonometry in children and adolescents. Thus, the SphygmoCor XCEL device could be
appropriate for assessing cf-PWV and cSP in the pediatric population.
PMID- 29939944
TI - Transactivation of Met signalling by semaphorin4D in human placenta: implications
for the pathogenesis of preeclampsia.
AB - OBJECTIVE: The signalling of the receptor tyrosine kinase Met is critical in
promoting trophoblast cell invasion, and the deficiency in HGF/Met signalling is
associated with preeclampsia. The semaphorin family member semaphorin4D (sema4D)
and its receptor Plexin-B1 have been reported to control tumour cell invasion by
coupling with Met. We hypothesized that sema4D/Plexin-B1 may promote trophoblast
invasion by activating Met, and downregulation of sema4D/Plexin-B1 may account
for the deficiency in Met signalling in preeclamptic placenta. METHODS: In this
study, Met and Erk activation and the expression of sema4D/Plexin-B1 in normal
and preeclamptic placentas were comparably measured. The role of sema4D in
trophoblast cell invasion and tubulogenesis was examined in vitro using the
Transwell invasion assay and tube formation assay in trophoblast-endothelial cell
co-culture model. RESULTS: Met, sema4D and Plexin-B1 co-localized in various
subtypes of human trophoblast cells, including villous trophoblasts and
extravillous trophoblasts (EVTs). In early-onset preeclampsia (E-PE) placentas,
the phosphorylated Met and Erk as well as sema4D and Plexin-B1 were much lower
than those in gestational week-matched preterm-labour (PTL) placentas. In human
trophoblast HTR8/SVneo cell line, sema4D could promote Met and Erk
phosphorylation as well as enhance trophoblast cell invasion and tubulogenesis
with endothelial cells. Moreover, the effect of sema4D on HTR8/SVneo could be
blocked by knocking down Met with specific siRNA. CONCLUSION: The crosstalk
between sema4D and Met could transactivate Met to promote trophoblast cell
invasion and differentiation, and decreased expression of sema4D and Plexin-B1
may be responsible for the deficiency in Met signalling and the development of
preeclampsia.
PMID- 29939945
TI - Habitual physical activity and central artery stiffening in older adults: the
Atherosclerosis Risk in Communities study.
AB - INTRODUCTION: Regular physical activity appears to attenuate or even reverse age
related arterial stiffening. Yet, it is not clear if the reduced stiffening
associated with habitual physical activity is also observed in community-dwelling
older adults. METHODS: Among 3893 older adults in a prospective cohort study, we
associated physical activity with measures of central arterial stiffness (via
carotid-femoral pulse wave velocity or cfPWV) and pressure pulsatility (via
central pulse pressure or cPP). We also examined the association of long-term
habitual physical activity, measured as persistence in physical activity levels
from mid-life to late-life, with cfPWV and cPP among 1747 participants. RESULTS:
The adjusted mean difference in cfPWV was lower, reflecting less arterial
stiffness, for those with moderate (beta = -0.30 m/s) or high (beta = -0.38 m/s)
physical activity compared with no physical activity. The adjusted mean
difference in cPP was also lower for those with high (beta = -2.49 mmHg) physical
activity, relative to no physical activity. Stronger effect estimates were
observed among those with persistent physical activity from mid-life to late
life. CONCLUSION: Higher physical activity in late-life, and habitual physical
activity from mid-life to late-life, is associated with lower central arterial
stiffness and pressure pulsatility in a large population-based sample of
community-dwelling older adults.
PMID- 29939946
TI - Childhood adiposity, adult adiposity, and the ACE gene insertion/deletion
polymorphism: evidence of gene-environment interaction effects on adult blood
pressure and hypertension status in adulthood.
AB - BACKGROUND: Genetic variants may modify the associations of adiposity measures
with blood pressure (BP) and hypertension. The insertion/deletion (I/D)
polymorphism in the angiotensin-converting enzyme (ACE) gene is an attractive
candidate. AIMS: To examine interaction effects between I/D polymorphism and
adiposity measures (BMI, waist circumference, waist-to-hip ratio, and skinfold
thickness) during childhood and adulthood in relation to adult BP and
hypertension. METHODS: Data were available for 4835 participants from three
prospective cohort studies. Multivariable linear regression models for adult SBP
and DBP, and multivariable logistic regression models for hypertension were fit
that included interaction effects between child or adult adiposity and I/D
polymorphism. RESULTS: Evidence for interaction effects on BP/hypertension were
found across the three studies. Compared with childhood measures, the effect
modification appeared to be more consistent when using adult adiposity. In
particular, the adverse effects of greater adult waist circumference on
increasing adult SBP and DBP appeared to be larger among carriers of ACE DD (or
GG) [adjusted linear regression coefficients 0.26, 95% CI (0.21-0.31) and 0.28
(0.24-0.32) for SBP and DBP, respectively] and ID (or AG) genotypes [0.25 (0.21
0.29) and 0.25 (0.21-0.28), respectively], whereas those with II (or AA)
genotypes had smaller effects [0.15 (0.09-0.21) and 0.19 (0.13-0.23)].
CONCLUSION: ACE genetic variation may modify the effect of adult adiposity on
increasing BP and risk of hypertension in adulthood. Individuals with ACE DD (or
GG) and/or ID (or AG) genotypes, compared with those with II (or AA) genotype,
appear more vulnerable to the impact of excess adiposity.
PMID- 29939947
TI - Bilateral Comparison of Vertical Jump Landings and Step-off Landings From Equal
Heights.
AB - Harry, JR, Silvernail, JF, Mercer, JA, and Dufek, JS. Bilateral comparison of
vertical jump landings and step-off landings from equal heights. J Strength Cond
Res 32(7): 1937-1947, 2018-The purpose of this investigation was to examine
kinetic, kinematic, and temporal parameters during vertical jump landings (VJL)
and step-off landings (STL) from equal heights. Five men (25.0 +/- 1.6 years; 1.7
+/- 0.4 m; 79.7 +/- 7.1 kg) and 5 women (20.8 +/- 1.6 years; 1.6 +/- 0.4 m; 68.5
+/- 7.1 kg) performed 15 VJL and 15 STL. Paired-samples t-tests (alpha = 0.05)
compared impact velocity and the times to the first (F1) and second (F2) peak
vertical ground reaction force magnitudes (tF1 and tF2) and the end of impact.
Two-way analyses of variance (alpha = 0.05) compared limb and task differences in
F1, F2, hip, knee, and ankle joint angles at ground contact, F1, F2, and the end
of impact, and hip, knee, and ankle joint displacements between contact and F1,
F1 and F2, and F2 and the end of impact. Impact velocity was not different
between STL and VJL, although STL produced a greater F1 and a more rapid tF2.
Greater hip, knee, and ankle flexion/dorsiflexion occurred during STL throughout
the majority of impact regardless of limb. Lesser hip, knee, and ankle joint
displacements occurred during STL regardless of limb between F1 and F2, whereas
greater joint displacement occurred between F2 and the end of impact. Lastly,
knee joint angles at ground contact differed between limbs during STL only.
Strength and conditioning professionals aiming to improve an athlete's
performance during sport-specific jump landings should consider the likely impact
attenuation outcomes before selecting STL or VJL in training.
PMID- 29939948
TI - Validity of Retrospective Session Rating of Perceived Exertion to Quantify
Training Load in youth Athletes.
AB - Scantlebury, S, Till, K, Sawczuk, T, Phibbs, P, and Jones, B. Validity of
retrospective session rating of perceived exertion to quantify training load in
youth athletes. J Strength Cond Res 32(7): 1975-1980, 2018-Youth athletes
frequently participate in multiple sports or for multiple teams within the same
sport. To optimize player development and minimize undesirable training outcomes
(e.g., overuse injuries), practitioners must be cognizant of an athlete's
training load within and outside their practice. This study aimed to establish
the validity of a 24-hour (s-RPE24) and 72-hour (s-RPE72) recall of session
rating of perceived exertion (s-RPE) against the criterion measure of s-RPE
collected 30 minutes' post training (s-RPE30). Thirty-eight adolescent athletes
provided a s-RPE30 following the first field based training session of the week.
Approximately 24 hours later subjects were asked to recall the intensity and
duration of the previous days training. The following week subjects once again
provided an s-RPE30 measure after training before recalling the intensity and
duration of the session approximately 72 hours later. A nearly perfect
correlation (0.98 [0.97-0.99]) was found between s-RPE30 and s-RPE24, with a
small typical error of estimate (TEE; 8.3% [6.9-10.5]) and trivial mean bias (
1.1% [-2.8 to 0.6]). Despite a large correlation between s-RPE30 and s-RPE72
(0.73 [0.59-0.82]) and a trivial mean bias (-0.2% [-6.8 to 6.8]), there was a
large TEE (35.3% [29.6-43.9]). s-RPE24 provides a valid measure of
retrospectively quantifying s-RPE; however, the large error associated with s
RPE72 suggests that it is not a suitable method for monitoring training load in
youth athletes.
PMID- 29939949
TI - Association Between Conditioning Capacities and Shooting Performance in
Professional Basketball Players: An Analysis of Stationary and Dynamic Shooting
Skills.
AB - Pojskic, H, Sisic, N, Separovic, V, and Sekulic, D. Association between
conditioning capacities and shooting performance in professional basketball
players: an analysis of stationary and dynamic shooting skills. J Strength Cond
Res 32(7): 1981-1992, 2018-Little is known about the influence of conditioning
capacities on shooting performance in basketball. The aim of this study was to
examine the relationship between different conditioning capacities and shooting
performance in professional basketball players. In this investigation, we
examined 38 males (all perimeter players; height: 185.5 +/- 6.73 cm; mass: 78.66
+/- 10.35 kg). Conditioning capacities were evaluated by tests of muscular
strength, aerobic endurance, jumping and throwing capacities, sprinting speed,
preplanned agility, anaerobic endurance, and fatigue resistance. Shooting
performance was evaluated using game statistics, as well as 6 tests of shooting
performance performed in controlled settings: (a) 3 tests of static (i.e.,
nonfatigued) shooting performance (standardized execution of 1- [S1], 2- [S2] and
3-point shots [S3] in stationary conditions), and (b) 3 tests of dynamic (i.e.,
fatigued) shooting performance (standardized execution of 1- [D1], 2- (D2), and 3
point shots [D3] in dynamic conditions). All 3 dynamic shooting tests and the S1
test were significantly (p <= 0.05) correlated with corresponding game
statistics. Multiple regression indicated that conditioning capacities were
significantly related to D1 (R = 0.36; p = 0.03), D2 (R = 0.44; p = 0.03), S3 (R
= 0.41; p = 0.02), and D3 (R = 0.39; p = 0.03) tests. Players with a higher
fatigue resistance achieved better results on the D1 test (beta = -0.37, p =
0.03). Preplanned agility (beta = -0.33, p = 0.04), countermovement jump (beta =
0.42, p = 0.03), and fatigue resistance (beta = -0.37, p = 0.02) were significant
predictors of D2 performance. The countermovement jump (beta = 0.39, p = 0.04),
medicine ball toss (beta = 0.34, p = 0.04), and anaerobic endurance (beta = 0.46,
p = 0.04) predicted the results of D3 performance. Jumping, throwing, and
anaerobic endurance capacities were good determinants of the skill of dynamic
shooting over a long distance. These findings emphasize the importance of
explosive power and anaerobic capacity as determinants of shooting performance in
high-level basketball players.
PMID- 29939950
TI - Race Profiles of Rowers During the 2014 Youth Olympic Games.
AB - Cerasola, D, Cataldo, A, Bellafiore, M, Traina, M, Palma, A, Bianco, A, and
Capranica, L. Race profiles of rowers during the 2014 Youth Olympic Games. J
Strength Cond Res 32(7): 2055-2060, 2018-Among the different factors affecting
the outcome of elite rowing competitions, pacing strategy plays a relevant role.
The purpose of this study was to analyze the race profiles of youth athletes
competing at the 2014 Youth Olympic Games over a distance of 1,000 m. According
to the competition outcome of sculling and sweep events, 96 youth (17-18 years)
rowers (48 male and 48 female) were divided into winner (W), not winner (NW),
qualified (Q), and not-qualified (NQ) athletes. The time during the 1,000-m race
distance was considered at 0-500 m (T1) and 500-1000 m (T2). The average speed of
T1 and T2 were normalized in relation to the average speed of the whole race. In
both sexes, W rowers showed higher (p > 0.05) T2 values (100.8 +/- 0.9%) with
respect to T1 (99.2 +/- 0.9%) ones. Female athletes showed a higher (p <= 0.05)
T1 with respect to T2 in NW, Q, and NQ, whereas male athletes exhibited a higher
T1 (p <= 0.05) than T2 speed only in NQ. While to be admitted to the final phase
of the competition, the rowers tended to favor a positive race strategy (88%);
during the final phase, a difference (p = 0.43) emerged for outcome, with the
majority of medalists (67%) adopting a negative race strategy. These results
suggest that winners have applied a different race strategy compared with the
other groups in consequence to a higher efficiency of anaerobic metabolism.
PMID- 29939951
TI - Quality and Safety in Health Care, Part XLII: Introduction to the Implantable
Cardioverter Defibrillator Registry.
AB - Implantable cardioverter defibrillators for both primary and secondary prevention
have been successful in decreasing sudden cardiac death. The Implantable
Cardioverter Defibrillator Registry was established partly for reimbursement for
primary prevention. However, the registry also has been helpful in better
understanding the risks and appropriate selection of patients to receive these
devices, serving as an impetus for quality improvement by giving outcome
information to the contributing institutions regarding their performance relative
to the national results, and increasing research. It is also expected to be
helpful to compare results from different devices and provide information to the
public.
PMID- 29939952
TI - Progression of Focal to Diffuse Thyroid Uptake Detected by 18F-FDG PET/CT:
Malignant Metastatic Disease or Benign Thyroiditis?
AB - A 49-year-old man was referred to our department for an assessment of a cerebral
metastasis of unknown primary with F-FDG PET/CT. This imaging led to detection of
a suspected pulmonary primary carcinoma, as well as an incidental left focal
thyroid uptake. An ultrasonography, performed a month later, revealed a
thyroiditis aspect. An anti-PD1 immunotherapy was also proposed 2 months later
after confirmation of a lung adenocarcinoma. A second baseline FDG PET/CT
surprisingly showed a diffuse thyroid uptake. A fine-needle aspiration biopsy of
thyroid parenchyma finally revealed a diffuse involvement from lung
adenocarcinoma (ie, primary lung metastasis to the thyroid gland).
PMID- 29939953
TI - Utility of 68Ga-PSMA-11 PET/CT in Imaging of Glioma-A Pilot Study.
AB - BACKGROUND: Imaging of gliomas remains challenging. The aim of the study was to
assess the feasibility of using Ga-PSMA-11 PET/CT for imaging gliomas. METHODS:
Fifteen patients with glioma from 2 centers were included in the study. Ten
patients were treated cases of glioblastoma with suspected recurrence. Two
patients were sent for assessing the nature (primary lesion/metastasis) of space
occupying lesion in the brain; 3 patients were imaged immediately after surgery
and before radiotherapy. Target-to-background ratios (TBR) for the brain lesions
were calculated using contralateral cerebellar uptake as background. RESULTS:
Among the 10 cases with suspected recurrence, scan was positive in 9, subsequent
surgery was done, and histopathology proved it to be true recurrence. In the scan
negative case on follow-up, no evidence of disease could be made clinically or
radiologically. Among the other cases the presence or absence of disease could be
unequivocally identified on the Ga-PSMA-11 brain scan and correlated with the
histopathology or other imaging. Apart from the visual assessment quantitative
assessment of the lesions with TBR also showed a significantly high TBR value for
those with true disease compared with those with no disease. CONCLUSIONS: In the
evaluation of gliomas, Ga-PSMA-11 PET/CT brain imaging is a potentially useful
imaging tool. The use of Ga-PSMA-11 brain PET/CT in evaluation of recurrent
glioma seems promising. Absence of physiological uptake of Ga-PSMA-11 in the
normal brain parenchyma results in high TBR values and consequently better
visualization of glioma lesions.
PMID- 29939955
TI - Demonstration of Treatment Response to Trans-arterial Radio-embolization (TARE)
on 68Ga-DOTANOC PET/CT in a Patient With Metastatic Neuroendocrine Tumor.
AB - Here we report a 31-year-old man with a peri-ampullary neuroendocrine tumor
(NET), who underwent Ga DOTANOC-PET/CT for recurrence evaluation, which revealed
isolated metastatic lesion in liver segment V. He underwent trans-arterial radio
embolization (TARE) of the isolated hepatic metastasis with Rhenium-microspheres
in a lipiodol matrix. The second Ga DOTANOC-PET/CT was performed one month after
the TARE therapy revealed resolution of the tracer uptake with good retention of
the lipiodol complex replacing the metastasis suggesting a complete response.
PMID- 29939954
TI - 18F-Fluciclovine Uptake by an Incidentally Detected Hepatocellular Carcinoma in a
Case of Biochemically Recurrent Prostate Cancer.
AB - Prostate cancer is one of the most common cancers affecting men worldwide with a
high recurrence rate following therapy. F-fluciclovine, is a US Food and Drug
Administration-approved radiopharmaceutical for PET imaging in biochemically
recurrent prostate cancer. It targets increased amino acid transporters in the
cell membrane of cancer cells. We report a case of incidentally detected
hepatocellular carcinoma showing F-fluciclovine uptake in a 71-year-old man with
biochemically recurrent prostate cancer.
PMID- 29939956
TI - Intramuscular Follicular Lymphoma.
AB - We present an interesting image of a painless growing mass of the right arm in a
76-year-old man. A musculoskeletal MRI of the right arm showed a 7.5 * 3-cm
homogeneous, well-defined mass, elongated along the course of muscle fascias and
independent of the adjacent bone. A core-needle biopsy was performed, and the
diagnosis of low-grade follicular lymphoma was established. Intramuscular
lymphoma should be integrated into the differential diagnosis of tumors
surrounding neurovascular structures, alongside peripheral nerve tumors and soft
tissue sarcoma. MRI and whole-body F-FDG PET/CT features provided useful
information to refine differential diagnosis in this case.
PMID- 29939957
TI - Detection of Metastatic Meningioma to the Liver Using 68Ga-DOTA-Octreotate
PET/CT.
AB - We present a case of metastatic meningioma detected on Ga-DOTA-octreotate PET. A
52-year-old woman presented with multiply recurrent multifocal meningioma. A
staging Ga-DOTATATE PET/CT demonstrated focal radiotracer uptake within the known
intracranial meningiomas. In addition, a DOTATATE-avid mass was found in the
liver that was biopsied, confirming metastatic meningioma. This report suggests
that Ga-DOTATATE PET/CT should be considered whenever screening meningioma
patients for metastases.
PMID- 29939958
TI - Chronic itch impairs mood and HPA axis function in mice: modulation by CRFR1
antagonist.
AB - Chronic itch is clinically correlated with the development of mood disorders such
as anxiety and depression. Nonetheless, whether this relevance exists in rodents
is unknown, and evidence demonstrating chronic itch can affect mood is lacking.
The aim of this study is to characterize the affective consequences of chronic
itch, and explore potential mechanisms and interventional strategy. We subjected
mice to chronic itch by repetitive cutaneous treatment with acetone and
diethylether followed by water (AEW) that models "dry skin." After 3 to 4 weeks
AEW treatment, the mice developed behavioral phenotypes of anxiety and depression
assessed by a battery of behavioral paradigms, such as light-dark box and forced
swim test. These behavioral symptoms of mood disturbance were independent of
cutaneous barrier disruption, but correlated well with the degree of the
irritating itch sensation. Although AEW mice showed normal circadian hypothalamic
pituitary-adrenal (HPA) axis activity, their neuroendocrine functionality was
dampened, including impaired endocrine stress responsivity, altered
neuroendocrine-immune interaction, and blunted corticosterone response to both
dexamethasone and CRF. Parameters of HPA functionality at the level of mRNA
transcripts are altered in stress-related brain regions of AEW mice, implying an
overdrive of central CRF system. Remarkably, chronic treatment of AEW mice with
antalarmin, a CRFR1 antagonist, ameliorated both their mood impairment and stress
axis dysfunction. This is the first evidence revealing mood impairment, HPA axis
dysfunction, and potential therapeutic efficacy by CRFR1 antagonist in mice with
chronic itch, thus providing a preclinical model to investigate the affective
consequence of chronic itch and the underlying mechanisms.
PMID- 29939959
TI - Efficacy of hypnosis on pain, wound-healing, anxiety, and stress in children with
acute burn injuries: a randomized controlled trial.
AB - No randomized controlled trial has investigated the efficacy of hypnosis for
reducing pain and improving wound-healing in children with burns. This randomized
controlled trial aimed to investigate whether hypnosis decreases pain, anxiety,
and stress and accelerates wound-healing in children undergoing burn wound
procedures. Children (4-16 years) with acute burns presenting for their first
dressing change were randomly assigned to a Hypnosis Group who received hypnosis
plus standard care or a Standard Care Group who received standard pharmacological
and nonpharmacological intervention. Repeated measures of pain intensity,
anxiety, stress, and wound-healing were taken at dressing changes until >=95%
wound re-epithelialization. Data for 62 children were analyzed on an intent-to
treat basis using Generalized Estimating Equations (n = 35 Standard Care Group; n
= 27 Hypnosis Group). An effect on the primary outcomes of pain and wound healing
was not supported {self-reported pain intensity largest Mean Difference [MD] =
0.85 (95% confidence interval [CI]: -1.91 to 0.22), P = 0.12; MD for re
epithelialization = -0.46 [95% CI: -4.27 to 3.35], P = 0.81}. Some support was
found for an effect on the secondary outcomes of preprocedural anxiety (MD =
0.80 [95% CI: -1.50 to -0.10], P = 0.03 before the second dressing change) and
heart rate as a measure of stress (MD = -15.20 [-27.20 to -3.20], P = 0.01 and MD
= -15.39 [-28.25 to -2.53], P = 0.02 before and after the third dressing change).
Hypnosis may be effective for decreasing preprocedural anxiety and heart rate in
children undergoing repeated pediatric wound care procedures but not for reducing
pain intensity or accelerating wound healing.
PMID- 29939960
TI - Location-specific responses to nociceptive input support the purposeful nature of
motor adaptation to pain.
AB - Movement is changed in pain, but the mechanisms remain unclear. Key questions are
unresolved such as whether activation can be inhomogeneously distributed within a
muscle in a manner that is specific to the location of noxious input. This study
addressed this question using high-density electromyography (EMG) to study
regional redistribution of muscle activation within the vasti muscles and changes
in knee extension force direction in response to noxious stimulation applied to
muscular and nonmuscular tissues around the knee. Fourteen participants performed
a low-force knee extension contraction at baseline, during, and after pain
induced in 4 locations (infrapatellar fat pad, vastus lateralis, distal vastus
medialis, or proximal vastus medialis). The knee extension force direction was
estimated from a 3-dimensional load cell positioned just above the ankle.
Regional muscle activation was estimated from amplitude of high-density surface
EMG signals from vastus medialis and lateralis. Pain-induced spatial variations
of activation were identified as the position of the 5 channels that showed the
largest decrease (or smallest increase) in amplitude from baseline to pain or
after pain. Knee extension force was produced more medially during pain after
infrapatellar pad injection only (P = 0.01). Preferential reduction of activation
of the distal region of vastus medialis was observed when distal vastus medialis
(P < 0.001) or vastus lateralis (P < 0.05) was injected. Both adaptations
persisted after pain resolution. These results support the hypothesis that
specific adaptation depends on the location of a noxious stimulus and imply that
recovery of pain is not necessarily concomitant with return of the EMG to prepain
patterns.
PMID- 29939961
TI - Efficacy of adding interoceptive exposure to intensive interdisciplinary
treatment for adolescents with chronic pain: a randomized controlled trial.
AB - Fear of pain plays an important role in the maintenance of chronic pain. It may
be reduced through exposure therapy. This 2-arm parallel samples randomized
controlled trial aimed to investigate whether interoceptive exposure (IE) therapy
enhances reductions in fear of pain (primary outcome), pain (pain intensity, pain
related disability, and school absence), and emotional characteristics (anxiety
and catastrophizing) when implemented as an adjunctive treatment in the context
of intensive interdisciplinary pain treatment for pediatric chronic pain
patients. N = 126 adolescents, aged 11 to 17 years, who were receiving standard
intensive interdisciplinary pain treatment were randomly assigned to either
receive additional IE (n = 64) or additional relaxation therapy (RT) (n = 62).
All patients were assessed at admission, discharge, and 3 months after discharge.
The data of N = 104 patients were analyzed. Significant large reductions were
found in the total score and subscale scores of the Fear of Pain Questionnaire
for Children in both study groups (eg, total score [range 0-60; IE/RT]: admission
M = 23.5/24.9; discharge M = 16.0/19.7; P < 0.001, (Equation is included in full
text article.)= 0.27) and mainly large reductions in pain characteristics. There
were no greater decreases in the IE group (P > 0.1). The exploratory analyses
revealed that the patients with high fear of pain before treatment (P < 0.05,
(Equation is included in full-text article.)> 0.03) and the patients with
abdominal pain (P < 0.04, (Equation is included in full-text article.)> 0.25)
showed greater decreases in their fear of pain (total and subscale score) in the
IE group than in the RT group. In conclusion, the results suggest that IE is not
particularly effective for all the pediatric chronic pain patients, but the
patients with high fear of pain before treatment and with abdominal pain strongly
benefit from this intervention.
PMID- 29939962
TI - Involvement of lysophosphatidic acid-induced astrocyte activation underlying the
maintenance of partial sciatic nerve injury-induced neuropathic pain.
AB - We have previously demonstrated that lysophosphatidic acid (LPA) plays key roles
in the initial mechanisms for neuropathic pain (NeuP) development. Here, we
examined whether LPA receptor mechanisms and LPA production are related to the
glial activation at a late stage after partial sciatic nerve ligation (pSNL) by
use of microglial inhibitor, Mac1-saporin or astrocyte inhibitor, and L-alpha
aminoadipate (L-AA). Although single intrathecal injection of LPA1/3 antagonist,
Ki-16425 did not affect the pain threshold at day 7 after the spinal cord injury,
repeated treatments of each compound gradually reversed the basal pain threshold
to the control level. The intrathecal administration of a microglia inhibitor,
Mac-1-saporin reversed the late hyperalgesia and LPA production at day 14 after
the pSNL, whereas L-AA inhibited the hyperalgesia, but had no effect on LPA
production. The involvement of LPA receptors in astrocyte activation in vivo was
evidenced by the findings that Ki-16425 treatments abolished the upregulation of
CXCL1 in activated astrocytes in the spinal dorsal horn of mice at day 14 after
the pSNL, and that Ki-16425 reversed the LPA-induced upregulation of several
chemokine gene expressions in primary cultured astrocytes. Finally, we found that
significant hyperalgesia was observed with intrathecal administration of primary
cultured astrocytes, which had been stimulated by LPA in a Ki-16425-reversible
manner. All these findings suggest that LPA production and LPA1/3 receptor
activation through differential glial mechanisms play key roles in the
maintenance as well as initiation mechanisms in NeuP.
PMID- 29939963
TI - Low- and high-threshold primary afferent inputs to spinal lamina III antenna-type
neurons.
AB - The dorsal horn of the spinal cord (laminae I-VI) processes diverse modalities of
nociceptive and nonnociceptive sensory information. Antenna-type neurons with
cell bodies located in lamina III and large dendritic trees extending from the
superficial lamina I to deep lamina IV are best shaped for the integration of a
wide variety of inputs arising from primary afferent fibers and intrinsic spinal
circuitries. Although the somatodendritic morphology, the hallmark of antenna
neurons, has been well studied, little is still known about the axon structure
and basic physiological properties of these cells. Here, we did whole-cell
recordings in a rat (P9-P12) spinal cord preparation with attached dorsal roots
to examine the axon course, intrinsic firing properties, and primary afferent
inputs of antenna cells. Nine antenna cells were identified from a large sample
of biocytin-filled lamina III neurons (n = 46). Axon of antenna cells showed
intensive branching in laminae III-IV and, in half of the cases, issued dorsally
directed collaterals reaching lamina I. Antenna cells exhibited tonic and
rhythmic firing patterns; single spikes were followed by hyperpolarization or
depolarization. The neurons received monosynaptic inputs from the low-threshold
Abeta afferents, Adelta afferents, as well as from the high-threshold Adelta, and
C afferents. When selectively activated, C-fiber-driven monosynaptic and
polysynaptic excitatory postsynaptic potentials were sufficiently strong to evoke
firing in the neurons. Thus, lamina III antenna neurons integrate low-threshold
and nociceptive high-threshold primary afferent inputs and can function as wide
dynamic range neurons able to directly connect deep dorsal horn with the major
nociceptive projection area lamina I.
PMID- 29939966
TI - Letter.
PMID- 29939964
TI - Influence of neuropathic pain on nicotinic acetylcholine receptor plasticity and
behavioral responses to nicotine in rats.
AB - Tobacco smoking is particularly evident in individuals experiencing chronic pain.
This complex relationship is poorly understood at both molecular and behavioral
levels. Here, we describe experiments aimed at understanding whether a chronic
pain state induces neuroadaptations into the brain or peripheral nerves that
involve nicotinic acetylcholine receptors (nAChRs) and whether these
neuroadaptations directly lead to increased vulnerability to nicotine addiction
or to the development of coping strategies to relieve pain symptoms. We found
that ligation of the rat L5 spinal nerve led to a dramatic downregulation in the
mRNA expression levels of all nAChR subunits examined in dorsal root ganglia and
a time-dependent downregulation of discrete subunits, particularly in the
cingulate cortex and the amygdala. Spinal nerve ligation and sham-operated rats
showed minor or no changes in patterns of acquisition and motivation for nicotine
taking. Spinal nerve ligation rats also showed similar vulnerability to nicotine
seeking as sham animals when reinstatement was induced by nicotine-associated
cues, but failed to reinstate lever pressing when relapse was induced by nicotine
priming. Spinal nerve ligation and sham rats were equally sensitive to nicotine
induced anxiety-like behavior and antinociception; however, nicotine produced a
potent and long-lasting antiallodynic effect in spinal nerve ligation rats. These
results demonstrate that chronic pain leads to plasticity of nAChRs that do not
directly facilitate nicotine addictive behaviors. Instead, nicotine potently
decreases allodynia, an effect that could lead to increased nicotine consumption
in chronic pain subjects.
PMID- 29939967
TI - New approaches in assessing food intake in epidemiology.
AB - PURPOSE OF REVIEW: A promising direction for improving dietary intake measurement
in epidemiologic studies is the combination of short-term and long-term dietary
assessment methods using statistical methods. Thereby, web-based instruments are
particularly interesting as their application offers several potential advantages
such as self-administration and a shorter completion time. The objective of this
review is to provide an overview of new web-based short-term instruments and to
describe their features. RECENT FINDINGS: A number of web-based short-term
dietary assessment tools for application in different countries and age-groups
have been developed so far. Particular attention should be paid to the underlying
database and the search function of the tool. Moreover, web-based instruments can
improve the estimation of portion sizes by offering several options to the user.
SUMMARY: Web-based dietary assessment methods are associated with lower costs and
reduced burden for participants and researchers, and show a comparable validity
with traditional instruments. When there is a need for a web-based tool
researcher should consider the adaptation of existing tools rather than
developing new instruments. The combination of short-term and long-term
instruments seems more feasible with the use of new technology.
PMID- 29939968
TI - Fecal microbial transplantation: an update.
AB - PURPOSE OF REVIEW: The purpose of this article is to provide an update on recent
developments in fecal microbiota transplantation (FMT) in the last year. RECENT
FINDINGS: Although FMT is an accepted treatment for recurrent Clostridium
difficile infection (CDI), recently it is also gaining acceptance for the
treatment of refractory CDI. FMT is showing promise in ulcerative colitis and is
experimental in many other conditions. The optimal practical aspects to enhance
the success of FMT are still being established. SUMMARY: The implication of
current research is that the indications of FMT may be extended to other
conditions in the future.
PMID- 29939969
TI - Taste perception and its effects on oral nutritional supplements in younger life
phases.
AB - PURPOSE OF REVIEW: The current review summarizes the importance of taste
perception with regard to acceptance of oral nutritional supplements (ONS) in
young children. We also shed light on how basic tastes may influence the
orosensory detection of ONS in the light of genetic variations, encoding for
different taste modalities, particularly for sweet and bitter (and fat), in
children. RECENT FINDINGS: Single nucleotide polymorphism (SNP) of bitter and
sweet taste receptor genes, that is, respectively, TAS2R38 and T1R2/T1R3, may
influence orosensory perception of 'bitter-made-sweet' ONS. The SNP of fat taste
receptor gene, that is, CD36, might communicate with bitter taste perception. The
emerging new sixth fat taste may interfere with obesity in children. SUMMARY:
Sweet and bitter taste modalities are innate cues, expressed by children from
birth to adolescence, either by a strong preference or by food aversion. Sweet
and bitter tastes also communicate with each other as sweeteners can mask bitter
phenotype. The fat preference, encoded by specific lingual taste receptors, is
also modulated, via its interaction with phenotype and genotype, by bitter taste.
Sodium salts might interact with bitter taste. Finally, the taste modalities will
impact on the intake of ONS in children as the taste phenotype changes in this
population, irrespective to genotype.
PMID- 29939970
TI - Fructooligosaccharides and appetite.
AB - PURPOSE OF REVIEW: Dietary fiber may play a role in obesity prevention through
reduction of body weight and control of appetite, however, not all fibers are
created equally, and characteristics of fiber such as viscosity, fermentability
and solubility may affect appetite differently. RECENT FINDINGS: Although early
studies supported that fructan fibers, including inulin, fructooligosaccharides,
and oligofructose affected satiety, more recent studies are less supportive. We
found that a higher dose of fiber such as oligofructose (16 g/day) is needed and
for a longer duration (12-16 weeks) to detect differences in appetite and
subsequent energy intake, whereas, practical amounts of fructooligosaccharides,
less than 10 g/day, generally do not affect satiety or food intake. It should be
noted that there are many sources of fructan fibers, both in native foods,
chicory roots, agave, and Jerusalem artichokes and isolated forms that vary in
chain length. SUMMARY: Fructan fibers, which include fructooligosaccharides,
oligofructose, and inulin, provided in low doses (<10 g/day), generally do not
affect measures of human appetite including satiety or food intake and should not
be recommended as a fiber with sole satiating power.
PMID- 29939971
TI - Analysis of mitochondrial respiratory function in tissue biopsies and blood
cells.
AB - PURPOSE OF REVIEW: The review provides an overview on latest methodological
strategies to assess mitochondrial respiratory function in tissue biopsies or
blood cells. In addition, it summarizes the recent literature related to this
topic. RECENT FINDINGS: Today, the study of mitochondrial function in key
metabolic active tissues has been become more relevant, with increasing focus in
clinical applications. In addition, assessment of mitochondrial function in blood
cells by respirometry might be a sensitive biomarker of disease progression. High
Resolution Respirometry provides a modern tool to study mitochondrial respiratory
physiology which allows direct measurement of cellular metabolic function during
health and disease. Moreover, standard operating procedures are required
regarding instrumental settings, sample collection and preparation, protocol
design and respirometric data analysis of mitochondrial respiratory function in
tissue biopsies (such as skeletal muscle, liver and adipose tissue), as well as
isolated blood cells. SUMMARY: Mitochondrial function is a key factor in many
metabolic diseases. Although various analytical approaches are available, certain
well-established protocols for isolated mitochondria are limited for the analysis
of mitochondrial function in tissue biopsies or blood cells. Thus, cautious
considerations in selecting appropriate protocols and analytical endpoints are
crucial for the interpretation of the gained data and to draw robust conclusions.
PMID- 29939972
TI - Comparison of Two Posterior Three-Point Fixation Techniques for Treating
Reducible Atlantoaxial Dislocation.
AB - STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare the outcomes
of C1-C2 transarticular screw combined with C1 laminar hook (TAS+ C1H) and C1-C2
transarticular screw combined with modified Gallie technique (TAS+ G) for
treating reducible atlantoaxial dislocation (AAD). SUMMARY OF BACKGROUND DATA:
Both TAS+ C1H and TAS+ G fixation were 3-point fixation techniques for AAD.
TAS+C1H technique was comparable to TAS+ G technique in biomechanics. However, it
is unknown whether it can achieve same outcomes as TAS+ G technique. METHODS:
Data of the 63 patients who underwent TAS+C1H or TAS+G fixation and fusion
because of AAD were retrospectively reviewed. Bone fusion time was recorded. The
outcomes evaluated by visual analog scale score for neck pain (VASSNP), Nurick
scale, neck stiffness (none/mild/severe), patient satisfaction and Neck
Disability Index (NDI) were compared between two groups. RESULTS: At the final
follow-up, bone graft fusion rates were 100% in both groups (P > 0.05). Nurick
scales were significantly improved in both groups (P < 0.05), but with no
significant differences between groups (P > 0.05). There were no significant
differences between two groups in VASSNP, neck stiffness, patient satisfaction,
or NDI (all P > 0.05). There were no complications related to the surgical
approach and instrumentation in either group. CONCLUSIONS: Both TAS+ C1H and TAS+
G fixation were effective in the treatment of reducible AAD. TAS+ C1H was safer
than TAS+ G because it could potentially reduce the risk of spinal cord and
venous plexus injury associated with sublaminar cables. LEVEL OF EVIDENCE: 3.
PMID- 29939973
TI - Fragility Fracture Risk in Elderly Patients with Cervical Myelopathy.
AB - STUDY DESIGN: Retrospective Review. OBJECTIVE: To identify and compare the
incidences of fragility fractures amongst three elderly populations: the general
population, patients with surgically treated cervical spondylotic myelopathy
(CSM), and patients with CSM not surgically treated. SUMMARY OF BACKGROUND DATA:
CSM is a common disease in the elderly. Progression of myelopathic symptoms,
including gait imbalance, can be a source of morbidity as it can lead to
increased falls. METHODS: Records of elderly patients with Medicare insurance
from 2005 to 2014 were retrospectively reviewed. Three mutually exclusive
populations of patients were identified for analysis, including a cohort of
patients with a diagnosis of CSM who were not treated with surgery; a cohort of
patients with CSM who were treated with surgery; and a group of control patients
who had never been treated with cervical spine surgery nor were diagnosed with
CSM. Incidence of fractures of the distal radius, proximal humerus, proximal
femur, and lumbar spine were assessed and compared between cohorts, adjusted by
age, sex, osteoporosis, dementia, cerebrovascular disease, and Charleson
Comorbidity Index. RESULTS: A total of 891,864 patients were identified, of which
60,332 had a diagnosis of CSM and 24,439 underwent cervical spine surgery.
Compared to general population controls, the 12-month adjusted odds of
experiencing at least one fragility fracture were 1.59 times higher in patients
with CSM who were not treated with surgery (P < 0.001). The analogous odds ratio
was 1.34 (P < 0.001) at 3 years. Compared to non-surgically treated CSM patients,
the odds of experiencing at least one fragility fracture were reduced to 0.89 in
surgically treated patients (P = 0.008). CONCLUSIONS: Fragility fractures are a
significant source of morbidity and mortality in elderly patients. CSM is
associated with increased rates of fragility fractures, though surgical
management of CSM may be protective against risk of fragility fracture. LEVEL OF
EVIDENCE: 3.
PMID- 29939974
TI - Three Methods of Pelvic Fixation for Scoliosis in Children with Cerebral Palsy:
Differences at 5-Year Follow-Up.
AB - STUDY DESIGN: Retrospective review. OBJECTIVE: To assess correction of pelvic
obliquity in children with cerebral palsy (CP) scoliosis postoperatively and 5
years after posterior spinal fusion with pelvic fixation using unit rods, sacral
alar-iliac (SAI) screws, or iliac screws. SUMMARY OF BACKGROUND DATA: There are
multiple options for pelvic fixation in children with scoliosis secondary to CP.
The long-term differences in outcomes between these fixation methods are still
unclear. METHODS: A multicenter review identified records of 70 children with CP
who underwent posterior spinal fusion for scoliosis using unit rods (n = 9), SAI
screws (n = 19), or iliac screws (n = 42). Patients younger than 18 years with 5
year follow-up were included. Pelvic obliquity and major coronal curve
measurements were compared using preoperative, (first erect) postoperative, and 5
year follow-up radiographs. Implant-related complications were noted. Alpha =
0.05. RESULTS: For all groups, there was a significant difference between
preoperative and postoperative pelvic obliquity that was maintained at 5 years.
At 5-year follow-up, pelvic obliquity was significantly higher in the IS group
(12 degrees ) compared with the unit rod group (4 degrees , p = 0.001) and SAI
screw group (6 degrees ) (p = 0.006). Implant-related complications were as
follows: unit rod group, 1 patient (reoperation); SAI screw group, none; iliac
screw group, 6 patients, including 3 cases of loss of connection between the rod
and the iliac screw, 2 prominent screws, and 1 loose screw. CONCLUSION:
Correction of pelvic obliquity for children with CP-related scoliosis was
achieved postoperatively using unit rods, SAI screws, and iliac screws. Implant
related complications and reoperations were most common in the iliac screw group.
At 5-year follow-up, the iliac screw group had loss of major curve correction and
less correction of pelvic obliquity than the unit rod and SAI screw groups. LEVEL
OF EVIDENCE: 3.
PMID- 29939975
TI - Comparison of Postoperative Outcomes between Primary MIS TLIF and MIS TLIF as a
Revision Procedure to Primary Decompression.
AB - STUDY DESIGN: Retrospective Cohort. OBJECTIVE: To compare postoperative
improvements in surgical and patient reported outcomes (PROs) between patients
undergoing minimally invasive laminectomy and minimally invasive transforaminal
lumbar interbody fusion (MIS TLIF) as a primary procedure to patients undergoing
MIS laminectomy and TLIF as a revision to primary lumbar decompression (LD).
SUMMARY OF BACKGROUND DATA: MIS TLIF and LD have demonstrated to be effective
surgical options for lumbar degenerative disease. However, some patients
undergoing LD experience recurrent symptoms and eventually require a revision
decompression with fusion. METHODS: A prospectively-maintained surgical database
of patients who underwent a primary or revision one-level MIS TLIF for
degenerative spinal pathology between 2014-2016 was reviewed. Consecutive
patients undergoing primary MIS TLIF and revision lumbar discectomy and/ or
laminectomy were matched in a 1-to-1 fashion to primary MIS TLIF patients who had
not undergone a previous lumbar decompression by age and preoperative diagnosis.
Differences in patient demographic, comorbidity, and perioperative
characteristics between procedure groups were assessed using Pearson's chi
squared analysis and Student's t-test for categorical and continuous variables,
respectively. Improvements in PROs from preoperative values were compared between
primary and revision cohorts using Student's t-tests. Pearson's chi-squared
analysis was utilized to compare rates of MCID achievement between procedure
groups. Statistical significant was set at p < 0.05. RESULTS: 52 patients were
included in this analysis. 26 underwent primary MIS laminectomy and TLIF and 26
underwent MIS TLIF with a revision decompression. No differences in baseline or
perioperative variables were observed. Revision and primary MIS TLIF patients
experienced similar improvements in PROs at all postoperative time points.
CONCLUSIONS: The results of the present study demonstrate patients undergoing
primary MIS TLIF with LD as a revision to a primary decompression experienced
similar postoperative improvements in PROs as compared to primary MIS TLIF
patients. This indicates a primary decompression does not compromise clinical
outcomes in patients undergoing MIS TLIF. As such, patients should not be
precluded from undergoing MIS TLIF based on the history of a previous lumbar
decompression. LEVEL OF EVIDENCE: 3.
PMID- 29939976
TI - Dilated Pupil as a Diagnostic Component of Brain Death-Does it Really Matter?
PMID- 29939977
TI - Performance of Electrical Velocimetry for Noninvasive Cardiac Output Measurements
in Perioperative Patients After Subarachnoid Hemorrhage.
AB - BACKGROUND: Fluid therapy guided by cardiac output measurements is of particular
importance for adequate cerebral perfusion and oxygenation in neurosurgical
patients. We examined the usefulness of a noninvasive electrical velocimetry (EV)
device based on the thoracic bioimpedance method for perioperative hemodynamic
monitoring in patients after aneurysmal subarachnoid hemorrhage. PATIENTS AND
METHODS: In total, 18 patients who underwent surgical clipping or endovascular
coiling for ruptured aneurysms were examined prospectively. Simultaneous cardiac
index (CI) measurements obtained with EV (CIEV) and reference transpulmonary
thermodilution (CITPTD) were compared. A total of 223 pairs of data were
collected. RESULTS: A significant correlation was found between CIEV and CITPTD
(r=0.86; P<0.001). Bland and Altman analysis revealed a bias between CIEV and
CITPTD of -0.06 L/min/m, with limits of agreement of +/-1.14 L/min/m and a
percentage error of 33%. Although the percentage error for overall data was
higher than the acceptable limit of 30%, subgroup analysis during the
postoperative phase showed better agreement (23% vs. 42% during the
intraprocedure phase). Four-quadrant plot and polar plot analyses showed fair-to
poor trending abilities (concordance rate of 90% to 91%, angular bias of +17
degrees, radial limits of agreement between +/-37 and +/-40 degrees, and polar
concordance rate of 72% to 75%), including the subgroup analysis. CONCLUSIONS:
Absolute CI values obtained from EV and TPTD are not interchangeable with TPTD
for perioperative use in subarachnoid hemorrhage patients. However, considering
the moderate levels of agreement with marginal trending ability during the early
postoperative phase, this user-friendly device can provide an attractive
monitoring option during neurocritical care.
PMID- 29939978
TI - Mortality Risk Using a Pediatric Quick Sequential (Sepsis-Related) Organ Failure
Assessment Varies With Vital Sign Thresholds.
AB - OBJECTIVES: We evaluated adapting the quick Sequential (Sepsis-Related) Organ
Failure Assessment score (fast respiratory rate, altered mental status, low blood
pressure) for pediatric use by selecting thresholds from three commonly used
definitions: Pediatric Logistic Organ Dysfunction 2, Pediatric Advanced Life
Support, and International Pediatric Sepsis Consensus Conference. We examined
their respective performance in identifying children who had a discharge
diagnosis of infection at high risk of mortality using PICU registry data, with
additional focus on the influence of age on performance. DESIGN: Analysis of
retrospective data obtained from the Virtual Pediatric Systems PICU database. The
performance in predicting observed mortality was assessed for the three candidate
approaches using receiver operating characteristics analysis, including age group
effects. SETTING: The Virtual Pediatric Systems database contains data on
diagnosis, clinical markers, and outcomes in prospectively collected clinical
records from 130 participating PICUs in the United States and Canada. PATIENTS:
Children who had a discharge diagnosis of infection in a participating PICU
between 2009 and 2014, for which all required data were available. INTERVENTIONS:
None. MEASUREMENTS AND MAIN RESULTS: Data from 40,228 children revealed an
overall mortality of 4.22%. Area under the receiver operating characteristics
curve (95% CI) was 0.760 (0.749-0.771) for Pediatric Logistic Organ Dysfunction 2
with mechanical ventilation, 0.700 (0.689-0.712) for Pediatric Advanced Life
Support, and 0.709 (0.696-0.721) for International Pediatric Sepsis Consensus
Conference. When split by age group, the performance of Pediatric Logistic Organ
Dysfunction 2 with mechanical ventilation was lowest in the youngest neonates
(under 1 wk old), with an area under the receiver operating characteristics curve
(95% CI) of 0.724 (0.656-0.791), and in the teenagers (13-18 yr), with an area
under the receiver operating characteristics curve of 0.710 (0.682-0.738), yet it
still outperformed Pediatric Advanced Life Support and International Pediatric
Sepsis Consensus Conference in both groups. CONCLUSIONS: Among critically ill
children who had a discharge diagnosis of infection in the PICU, quick Sequential
(Sepsis-Related) Organ Failure Assessment score performs best when using the
Pediatric Logistic Organ Dysfunction 2 age thresholds with mechanical
ventilation, while all definitions performed worse at extremes of pediatric age.
Thus, mortality risk varies with vital sign thresholds, and although Pediatric
Logistic Organ Dysfunction 2 with mechanical ventilation performed marginally
better, it is unlikely to be of use to clinicians. More work is needed to develop
a robust and relevant pediatric sepsis risk score.
PMID- 29939979
TI - Comparison of Ultrasound, Radiography, and Clinical Investigations in the
Diagnosis of Early Rheumatoid Synovitis in Patients with Nonspecific
Musculoskeletal Symptoms: A Multicenter Cross-Sectional Study.
AB - BACKGROUND Early diagnosis and treatment of rheumatoid synovitis can reduce the
progression of rheumatoid arthritis (RA). However, in the early stages of
rheumatoid synovitis, patients may only have non-specific musculoskeletal
symptoms, and plain film radiographs may not detect early synovial changes. The
aim of this study was to compare the sensitivity and specificity of ultrasound
with radiography, and clinical investigations in the detection of rheumatoid
synovitis in patients presenting with nonspecific musculoskeletal symptoms.
MATERIAL AND METHODS This was a non-randomized, cross-sectional, clinical study
that included 189 patients who had nonspecific musculoskeletal symptoms. All
patients underwent clinical investigations, postero-anterior and dorsal
radiographic imaging, and bilateral grey-scale ultrasound examinations of the
third and second metacarpophalangeal (MCP) joints, the third and the second
proximal interphalangeal (PIP) joints, the second and the fifth
metatarsophalangeal (MTP) joints, and the wrist. RESULTS There was no clear
predictive value for detection of early synovitis by clinical investigations
alone. Plain film radiography of patients only provided accurate information of
joint erosions but less information for synovitis. Grey-scale ultrasound was more
effective at detecting early synovitis compared with clinical investigations
(p=0.00015; q=4.548) and compared with plain film radiography (p=0.0002;
q=4.537), and quantified the synovial changes. The predictive values of plain
film radiography and clinical investigations had 0.43 and 0.24 sensitivity and 0
specificity compared with ultrasound. CONCLUSIONS The findings of this study
support the use of grey-scale ultrasound in the detection of early rheumatoid
synovitis of the fingers and the wrist.
PMID- 29939980
TI - Prevention of Hepatitis B Virus Infection in the United States: Recommendations
of the Advisory Committee on Immunization Practices.
AB - HEPATITIS B VIRUS (HBV) IS TRANSMITTED VIA BLOOD OR SEXUAL CONTACT. PERSONS WITH
CHRONIC HBV INFECTION ARE AT INCREASED RISK FOR CIRRHOSIS AND LIVER CANCER AND
REQUIRE MEDICAL CARE. THIS REPORT UPDATES AND SUMMARIZES PREVIOUSLY PUBLISHED
RECOMMENDATIONS FROM THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) AND
CDC REGARDING THE PREVENTION OF HBV INFECTION IN THE UNITED STATES. ACIP
RECOMMENDS TESTING ALL PREGNANT WOMEN FOR HEPATITIS B SURFACE ANTIGEN (HBSAG),
AND TESTING HBSAG-POSITIVE PREGNANT WOMEN FOR HEPATITIS B VIRUS DEOXYRIBONUCLEIC
ACID (HBV DNA); ADMINISTRATION OF HEPB VACCINE AND HEPATITIS B IMMUNE GLOBULIN
(HBIG) FOR INFANTS BORN TO HBV-INFECTED WOMEN WITHIN 12 HOURS OF BIRTH, FOLLOWED
BY COMPLETION OF THE VACCINE SERIES AND POSTVACCINATION SEROLOGIC TESTING;
UNIVERSAL HEPATITIS B VACCINATION WITHIN 24 HOURS OF BIRTH, FOLLOWED BY
COMPLETION OF THE VACCINE SERIES; AND VACCINATION OF CHILDREN AND ADOLESCENTS
AGED <19 YEARS WHO HAVE NOT BEEN VACCINATED PREVIOUSLY. ACIP RECOMMENDS
VACCINATION OF ADULTS AT RISK FOR HBV INFECTION, INCLUDING UNIVERSAL VACCINATION
OF ADULTS IN SETTINGS IN WHICH A HIGH PROPORTION HAVE RISK FACTORS FOR HBV
INFECTION AND VACCINATION OF ADULTS REQUESTING PROTECTION FROM HBV WITHOUT
ACKNOWLEDGMENT OF A SPECIFIC RISK FACTOR. THESE RECOMMENDATIONS ALSO PROVIDE CDC
GUIDANCE FOR POSTEXPOSURE PROPHYLAXIS FOLLOWING OCCUPATIONAL AND OTHER EXPOSURES.
THIS REPORT ALSO BRIEFLY SUMMARIZES PREVIOUSLY PUBLISHED AMERICAN ASSOCIATION FOR
THE STUDY OF LIVER DISEASEST GUIDELINES FOR MATERNAL ANTIVIRAL THERAPY TO REDUCE
PERINATAL HBV TRANSMISSION.
PMID- 29939981
TI - The role of inferior frontal junction in controlling the spatially global effect
of feature-based attention in human visual areas.
AB - Feature-based attention has a spatially global effect, i.e., responses to stimuli
that share features with an attended stimulus are enhanced not only at the
attended location but throughout the visual field. However, how feature-based
attention modulates cortical neural responses at unattended locations remains
unclear. Here we used functional magnetic resonance imaging (fMRI) to examine
this issue as human participants performed motion- (Experiment 1) and color-
(Experiment 2) based attention tasks. Results indicated that, in both
experiments, the respective visual processing areas (middle temporal area [MT+]
for motion and V4 for color) as well as early visual, parietal, and prefrontal
areas all showed the classic feature-based attention effect, with neural
responses to the unattended stimulus significantly elevated when it shared the
same feature with the attended stimulus. Effective connectivity analysis using
dynamic causal modeling (DCM) showed that this spatially global effect in the
respective visual processing areas (MT+ for motion and V4 for color),
intraparietal sulcus (IPS), frontal eye field (FEF), medial frontal gyrus (mFG),
and primary visual cortex (V1) was derived by feedback from the inferior frontal
junction (IFJ). Complementary effective connectivity analysis using Granger
causality modeling (GCM) confirmed that, in both experiments, the node with the
highest outflow and netflow degree was IFJ, which was thus considered to be the
source of the network. These results indicate a source for the spatially global
effect of feature-based attention in the human prefrontal cortex.
PMID- 29939982
TI - Descending pathways generate perception of and neural responses to weak sensory
input.
AB - Natural sensory stimuli frequently consist of a fast time-varying waveform whose
amplitude or contrast varies more slowly. While changes in contrast carry
behaviorally relevant information necessary for sensory perception, their
processing by the brain remains poorly understood to this day. Here, we
investigated the mechanisms that enable neural responses to and perception of low
contrast stimuli in the electrosensory system of the weakly electric fish
Apteronotus leptorhynchus. We found that fish reliably detected such stimuli via
robust behavioral responses. Recordings from peripheral electrosensory neurons
revealed stimulus-induced changes in firing activity (i.e., phase locking) but
not in their overall firing rate. However, central electrosensory neurons
receiving input from the periphery responded robustly via both phase locking and
increases in firing rate. Pharmacological inactivation of feedback input onto
central electrosensory neurons eliminated increases in firing rate but did not
affect phase locking for central electrosensory neurons in response to low
contrast stimuli. As feedback inactivation eliminated behavioral responses to
these stimuli as well, our results show that it is changes in central
electrosensory neuron firing rate that are relevant for behavior, rather than
phase locking. Finally, recordings from neurons projecting directly via feedback
to central electrosensory neurons revealed that they provide the necessary input
to cause increases in firing rate. Our results thus provide the first
experimental evidence that feedback generates both neural and behavioral
responses to low-contrast stimuli that are commonly found in the natural
environment.
PMID- 29939983
TI - Forecasting the effectiveness of indoor residual spraying for reducing dengue
burden.
AB - BACKGROUND: Historically, mosquito control programs successfully helped contain
malaria and yellow fever, but recent efforts have been unable to halt the spread
of dengue, chikungunya, or Zika, all transmitted by Aedes mosquitoes. Using a
dengue transmission model and results from indoor residual spraying (IRS) field
experiments, we investigated how IRS-like campaign scenarios could effectively
control dengue in an endemic setting. METHODS AND FINDINGS: In our model, we
found that high levels of household coverage (75% treated once per year), applied
proactively before the typical dengue season could reduce symptomatic infections
by 89.7% (median of 1000 simulations; interquartile range [IQR]:[83.0%, 94.8%])
in year one and 78.2% (IQR: [71.2%, 88.0%]) cumulatively over the first five
years of an annual program. Lower coverage had correspondingly lower
effectiveness, as did reactive campaigns. Though less effective than preventative
campaigns, reactive and even post-epidemic interventions retain some
effectiveness; these campaigns disrupt inter-seasonal transmission, highlighting
an off-season control opportunity. Regardless, none of the campaign scenarios
maintain their initial effectiveness beyond two seasons, instead stabilizing at
much lower levels of benefit: in year 20, median effectiveness was only 27.3%
(IQR: [-21.3%, 56.6%]). Furthermore, simply ceasing an initially successful
program exposes a population with lowered herd immunity to the same historical
threat, and we observed outbreaks more than four-fold larger than pre
intervention outbreaks. These results do not take into account evolving
insecticide resistance, thus long-term effectiveness may be lower if new,
efficacious insecticides are not developed. CONCLUSIONS: Using a detailed agent
based dengue transmission model for Yucatan State, Mexico, we predict that high
coverage indoor residual spraying (IRS) interventions can largely eliminate
transmission for a few years, when applied a few months before the typical
seasonal epidemic peak. However, vector control succeeds by preventing
infections, which precludes natural immunization. Thus, as a population benefits
from mosquito control, it gradually loses naturally acquired herd immunity, and
the control effectiveness declines; this occurs across all of our modeled
scenarios, and is consistent with other empirical work. Long term control that
maintains early effectiveness would require some combination of increasing
investment, complementary interventions such as vaccination, and control programs
across a broad region to diminish risk of importation.
PMID- 29939984
TI - Exploring the single-cell RNA-seq analysis landscape with the scRNA-tools
database.
AB - As single-cell RNA-sequencing (scRNA-seq) datasets have become more widespread
the number of tools designed to analyse these data has dramatically increased.
Navigating the vast sea of tools now available is becoming increasingly
challenging for researchers. In order to better facilitate selection of
appropriate analysis tools we have created the scRNA-tools database (www.scRNA
tools.org) to catalogue and curate analysis tools as they become available. Our
database collects a range of information on each scRNA-seq analysis tool and
categorises them according to the analysis tasks they perform. Exploration of
this database gives insights into the areas of rapid development of analysis
methods for scRNA-seq data. We see that many tools perform tasks specific to
scRNA-seq analysis, particularly clustering and ordering of cells. We also find
that the scRNA-seq community embraces an open-source and open-science approach,
with most tools available under open-source licenses and preprints being
extensively used as a means to describe methods. The scRNA-tools database
provides a valuable resource for researchers embarking on scRNA-seq analysis and
records the growth of the field over time.
PMID- 29939985
TI - Inactivation of Pichia rhodanensis in relation to membrane and intracellular
compounds due to microchip pulsed electric field (MPEF) treatment.
AB - The effect of microchip pulsed electric field (MPEF) treatment on lethal and
sublethal injury of Pichia rhodanensis (P. rhodanensis) were employed under 100
500 V for 20-100 pulses and the underlying mechanism of MPEF treatment was
investigated as well. A 6.48 log10 reduction of P. rhodanensis was achieved at
500V for 80 pulse. The fluorescent staining with Propidium Iodide (PI) verified
that the rate of sublethal injury cells maximum up to 27.2% under 200 V. MPEF can
cause the damage of cell morphology and ultrastructure, meanwhile causing a
decrease in cellular enzymes, antioxidant enzyme activity and cell membrane
fluidity. The leakage of intracellular compounds (protein, nucleic acid, K+,
Mg2+) and Ca2+-ATPase gradually increased as the growth of voltage, especially
the proportion of protein in the supernatants increased from 2.0% to 26.4%. Flow
cytometry analysis showed that MPEF has significant effect on membrane potential,
but no obvious influence on non-specific esterase. MPEF can cause the changing of
the secondary structure of protein, at the same time, double helix structure of
DNA became loose and unwinding. These results provide a theoretical guidance for
the widespread using of MPEF technology in the application of a non-thermal
processing technique for food.
PMID- 29939986
TI - Visual attention is not deployed at the endpoint of averaging saccades.
AB - The premotor theory of attention postulates that spatial attention arises from
the activation of saccade areas and that the deployment of attention is the
consequence of motor programming. Yet attentional and oculomotor processes have
been shown to be dissociable at the neuronal level in covert attention tasks. To
investigate a potential dissociation at the behavioral level, we instructed human
participants to move their eyes (saccade) towards 1 of 2 nearby, competing
saccade targets. The spatial distribution of visual attention was determined
using oriented visual stimuli presented either at the target locations, between
them, or at several other equidistant locations. Results demonstrate that
accurate saccades towards one of the targets were associated with presaccadic
enhancement of visual sensitivity at the respective saccade endpoint compared to
the nonsaccaded target location. In contrast, averaging saccades, landing between
the 2 targets, were not associated with attentional facilitation at the saccade
endpoint. Rather, attention before averaging saccades was equally deployed at the
2 target locations. Taken together, our results reveal that visual attention is
not obligatorily coupled to the endpoint of a subsequent saccade. Rather, our
results suggest that the oculomotor program depends on the state of attentional
selection before saccade onset and that saccade averaging arises from unresolved
attentional selection.
PMID- 29939987
TI - Heat stress transcripts, differential expression, and profiling of heat stress
tolerant gene TaHsp90 in Indian wheat (Triticum aestivum L.) cv C306.
AB - To generate a genetic resource of heat stress responsive genes/ESTs, suppression
subtractive hybridization (SSH) library was constructed in a heat and drought
stress tolerant Indian bread wheat cultivar C306. Ninety three days old plants
during grain filling stage were subjected to heat stress at an elevated
temperature of 37 degrees C and 42 degrees C for different time intervals (30
min, 1h, 2h, 4h, and 6h). Two subtractive cDNA libraries were prepared with RNA
isolated from leaf samples at 37 degrees C and 42 degrees C heat stress. The ESTs
obtained were reconfirmed by reverse northern dot blot hybridization. A total of
175 contigs and 403 singlets were obtained from 1728 ESTs by gene ontology
analysis. Differential expression under heat stress was validated for a few
selected genes (10) by qRT-PCR. A transcript showing homology to Hsp90 was
observed to be upregulated (7.6 fold) under heat stress in cv. C306. CDS of
TaHsp90 (Accession no. MF383197) was isolated from cv. C306 and characterized.
Heterologous expression of TaHsp90 was validated in E. coli BL21 and confirmed by
protein gel blot and MALDI-TOF analysis. Computational based analysis was carried
out to understand the molecular functioning of TaHsp90. The heat stress
responsive SSH library developed led to identification of a number of heat
responsive genes/ESTs, which can be utilized for unravelling the heat tolerance
mechanism in wheat. Gene TaHsp90 isolated and characterized in the present study
can be utilized for developing heat tolerant transgenic crops.
PMID- 29939988
TI - Integrated approach in the control and management of skin neglected tropical
diseases in Lalo, Benin.
AB - BACKGROUND: Neglected Tropical Diseases (NTDs) are a group of several
communicable diseases prevalent in the tropical and subtropical areas. The co
endemicity of these diseases, the similarity of the clinical signs, and need to
maximize limited financial and human resources have necessitated implementation
of integrated approach. Our study aims to share the lessons of this integrated
approach in the fight against Buruli ulcer (BU), leprosy and yaws in a rural
district in Benin. METHODS: It is a cross-sectional study using a single set of
activities data conducted from May 2016 to December 2016. Health workers and
community health volunteers involved in this study were trained on integrated
approach of the Buruli ulcer, leprosy and yaws. Village chiefs were briefed about
the activity. The trained team visited the villages and schools in the district
of Lalo in Benin. After the education and awareness raising sessions, all persons
with a skin lesion who presented voluntarily to the team were carefully examined
in a well-lit area which respected their privacy. Suspected cases were tested as
needed. The socio-demographic information and the characteristics of the lesions
were collected using a form. A descriptive analysis of the epidemiological,
clinical and laboratory variables of the cases was made using Excel 2013 and SPSS
version 22.00. PRINCIPAL FINDINGS: In the study period, 1106 people were
examined. The median (IQR) age of those examined was 11 (8; 27) years. Of 34
(3.1%) suspected BU cases, 15 (1.4%) were confirmed by PCR. Only three cases of
leprosy were confirmed. The 185 (16.7%) suspected cases of yaws were all negative
with the rapid test. The majority of cases were other skin conditions, including
fungal infections, eczema and traumatic lesions. CONCLUSION: The integrated
approach of skin NTD allows optimal use of resources and surveillance of these
diseases. Sustaining this skin NTD integrated control will require the training
of peripheral health workers not only on skin NTD but also on basic dermatology.
PMID- 29939989
TI - Polymorphisms and haplotypes in the promoter of the TNF-alpha gene are associated
with disease severity of severe fever with thrombocytopenia syndrome in Chinese
Han population.
AB - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious
disease that is caused by a novel bunyavirus, SFTSV. We assessed whether the
single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF
alpha) were associated with risk to severity of SFTS. Five TNF-alpha SNPs (SNP1:
T-1031C; SNP2: C-863A; SNP3: C-857T; SNP4: G-308A; SNP5: G-238A) were genotyped
in 987 hospitalized SFTS patients and 633 asymptomatic/mild SFTSV-infected
subjects of Chinese Han origin. Multivariate logistic regression analysis was
used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95%
CIs). The hospitalized SFTS patients had significantly lower frequency of G-238A
A allele than those with mild/asymptomatic infection (P = 0.006). Furthermore, T
1031C C allele (P < 0.001) and G-238A A allele (P < 0.001) were significantly
associated with decreased risk of death. Multiple haplotypes were significantly
associated with decreased risk of SFTS hospital admission (SNP1-2, CC; SNP1-3,
CCC; SNP1-4, CCCG; SNP1-5, CCCGA; SNP2-4, CCGA; SNP3-5, CGA; SNP4-5, GA) and
death (SNP1-2, CA; SNP1-3, CAG; SNP1-4, CACG; SNP1-5, CACGG; SNP2-3, AC; SNP2-4,
ACG; SNP2-5, ACGG) after correction for multiple comparisons. By using the ELISA
assay, we observed that TNF-alpha concentration of hospitalized patients was
significantly increased in acute phase than in convalescent phase (P < 0.001).
Elevated TNF-alpha concentration was also revealed from fatal patients (P <
0.001). The -238A allele was associated with decreased serum TNF-alpha levels in
SFTS patients in acute phase (P = 0.01). Our findings suggest that polymorphisms
in TNF-alpha gene may play a role in mediating the risk to disease severity of
SFTS in Chinese Han population.
PMID- 29939990
TI - Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker
study.
AB - The biological pathways involved in amyotrophic lateral sclerosis (ALS) remain
elusive and diagnostic decision-making can be challenging. Gene expression
studies are valuable in overcoming such challenges since they can shed light on
differentially regulated pathways and may ultimately identify valuable
biomarkers. This two-stage transcriptome-wide study, including 397 ALS patients
and 645 control subjects, identified 2,943 differentially expressed transcripts
predominantly involved in RNA binding and intracellular transport. When batch
effects between the two stages were overcome, three different models (support
vector machines, nearest shrunken centroids, and LASSO) discriminated ALS
patients from control subjects in the validation stage with high accuracy. The
models' accuracy reduced considerably when discriminating ALS from diseases that
mimic ALS clinically (N = 75), nor could it predict survival. We here show that
whole blood transcriptome profiles are able to reveal biological processes
involved in ALS. Also, this study shows that using these profiles to
differentiate between ALS and mimic syndromes will be challenging, even when
taking batch effects in transcriptome data into account.
PMID- 29939991
TI - Seropositivity of Brucella spp. and Leptospira spp. antibodies among abattoir
workers and meat vendors in the city of Mwanza, Tanzania: A call for one health
approach control strategies.
AB - INTRODUCTION: Brucellosis and leptospirosis are among neglected tropical zoonotic
diseases particularly in the resource limited countries. Despite being endemic in
these countries, there is paucity of information on its magnitude. This study
investigated seropositivity of Brucella spp. and Leptospira spp., and associated
factors among abattoir workers and meat vendors in the city of Mwanza, Tanzania.
METHODOLOGY: A community based cross-sectional study was conducted in Mwanza city
from May to July 2017. Socio-demographic and other relevant information were
collected. Detection of Brucella spp. and Leptospira spp. antibodies were done
using slide agglutination test and microscopic agglutination test, respectively.
Data were analyzed using STATA version 13 Software. FINDINGS: A total of 250
participants (146 abattoir workers and 104 meat vendors) were enrolled with
median age of 31 (IQR: 25-38) years. The overall, seropositivity of Brucella spp.
antibodies was 48.4% (95% Cl: 42-54). Seropositivity of B. abortus was
significantly higher than that of B. melitensis (46.0%, 95%Cl: 39-52 vs. 23.6%,
95% Cl: 18-28, P<0.001) while seropositivity of both species was 21.2% (95%Cl: 16
26). The seropositivity of Leptospira spp. was 10.0% (95% CI: 6-13) with
predominance of Leptospira kirschneri serovar Sokoine which was detected in 7.2%
of the participants. Being abattoir worker (OR: 2.19, 95% CI 1.06-4.54, p =
0.035) and long work duration (OR: 1.06, 95%CI: 1.01-1.11, p = 0.014) predicted
presence of both B.abortus and B. melitensis antibodies. Only being married (p =
0.041) was significantly associated with seropositivity of Leptospira spp.
Primary education was the only factor independently predicted presence of
Brucella spp. antibodies among abattoir workers on sub-analysis of occupational
exposure. None of factors were found to be associated with presence of Brucella
spp. antibodies among meat vendors on sub-analysis. CONCLUSION: Seropositivity of
B.abortus antibodies among abattoir workers and meat vendors is high and seem to
be a function of being abattoir worker, having worked for long duration in the
abattoir and having primary education. In addition, a significant proportion of
abattoir workers and meat vendors in the city was seropositive for Leptospira
kirschneri serovar Sokoine. There is a need to consider 'one health approach' in
devising appropriate strategies to control these diseases in the developing
countries.
PMID- 29939992
TI - Inositol polyphosphates regulate and predict yeast pseudohyphal growth
phenotypes.
AB - Pseudohyphal growth is a nutrient-regulated program in which budding yeast form
multicellular filaments of elongated and connected cells. Filamentous growth is
required for virulence in pathogenic fungi and provides an informative model of
stress-responsive signaling. The genetics and regulatory networks modulating
pseudohyphal growth have been studied extensively, but little is known regarding
the changes in metabolites that enable pseudohyphal filament formation. Inositol
signaling molecules are an important class of metabolite messengers encompassing
highly phosphorylated and diffusible inositol polyphosphates (InsPs). We report
here that the InsP biosynthesis pathway is required for wild-type pseudohyphal
growth. Under nitrogen-limiting conditions that can induce filamentation, InsPs
exhibit characteristic profiles, distinguishing the InsP7 pyrophosphate isoforms
1PP-InsP5 and 5PP-InsP5. Deletion and overexpression analyses of InsP kinases
identify elevated levels of 5PP-InsP5 relative to 1PP-InsP5 in mutants exhibiting
hyper-filamentous growth. Overexpression of KCS1, which promotes formation of
inositol pyrophosphates, is sufficient to drive pseudohyphal filamentation on
medium with normal nitrogen levels. We find that the kinases Snf1p (AMPK), Kss1p,
and Fus3p (MAPKs), required for wild-type pseudohyphal growth, are also required
for wild-type InsP levels. Deletion analyses of the corresponding kinase genes
indicate elevated InsP3 levels and an absence of exaggerated 5PP-InsP5 peaks in
trace profiles from snf1Delta/Delta and kss1Delta/Delta mutants exhibiting
decreased pseudohyphal filamentation. Elevated 5PP-InsP5:1PP-InsP5 ratios are
present in the hyperfilamentous fus3 deletion mutant. Collectively, the data
identify the presence of elevated 5PP-InsP5 levels relative to other inositol
pyrophosphates as an in vivo marker of hyper-filamentous growth, while providing
initial evidence for the regulation of InsP signaling by pseudohyphal growth
kinases.
PMID- 29939994
TI - Removing contaminants from databases of draft genomes.
AB - Metagenomic sequencing of patient samples is a very promising method for the
diagnosis of human infections. Sequencing has the ability to capture all the DNA
or RNA from pathogenic organisms in a human sample. However, complete and
accurate characterization of the sequence, including identification of any
pathogens, depends on the availability and quality of genomes for comparison.
Thousands of genomes are now available, and as these numbers grow, the power of
metagenomic sequencing for diagnosis should increase. However, recent studies
have exposed the presence of contamination in published genomes, which when used
for diagnosis increases the risk of falsely identifying the wrong pathogen. To
address this problem, we have developed a bioinformatics system for eliminating
contamination as well as low-complexity genomic sequences in the draft genomes of
eukaryotic pathogens. We applied this software to identify and remove human,
bacterial, archaeal, and viral sequences present in a comprehensive database of
all sequenced eukaryotic pathogen genomes. We also removed low-complexity genomic
sequences, another source of false positives. Using this pipeline, we have
produced a database of "clean" eukaryotic pathogen genomes for use with
bioinformatics classification and analysis tools. We demonstrate that when
attempting to find eukaryotic pathogens in metagenomic samples, the new database
provides better sensitivity than one using the original genomes while offering a
dramatic reduction in false positives.
PMID- 29939993
TI - Genetic diversity and spatial-temporal distribution of Yersinia pestis in Qinghai
Plateau, China.
AB - BACKGROUND: Plague, caused by the bacterium Yersinia pestis, is a highly
infectious, zoonotic disease. Hundreds of human plague cases are reported across
the world annually. Qinghai Plateau is one of the most severely affected plague
regions in China, with more than 240 fatal cases of Y. pestis in the last 60
years. Conventional epidemiologic analysis has effectively guided the prevention
and control of local plague transmission; however, molecular genetic analysis is
more effective for investigating population diversity and transmission. In this
report, we employed different genetic markers to analyze the population structure
of Y. pestis in Qinghai Plateau. METHODOLOGY/PRINCIPAL FINDING: We employed a two
step hierarchical strategy to analyze the phylogeny of 102 Qinghai Plateau
isolates of Y. pestis, collected between 1954 and 2011. First, we defined the
genealogy of Y. pestis by constructed minimum spanning tree based on 25 key SNPs.
Seven groups were identified, with group 1.IN2 being identified as the dominant
population. Second, two methods, MLVA and CRISPR, were applied to examine the
phylogenetic detail of group 1.IN2, which was further divided into three
subgroups. Subgroups of 1.IN2 revealed a clear geographic cluster, possibly
associated with interaction between bacteriophage and Y. pestis. More recently,
Y. pestis populations appear to have shifted from the east toward the center and
west of Qinghai Plateau. This shift could be related to destruction of the local
niche of the original plague focus through human activities. Additionally, we
found that the abundance and relative proportion of 1.IN2 subgroups varied by
decade and might be responsible for the fluctuations of plague epidemics in
Qinghai Plateau. CONCLUSION/SIGNIFICANCE: Molecular genotyping methods provided
us with detailed information on population diversity and the spatial-temporal
distribution of dominant populations of Y. pestis, which will facilitate future
surveillance, prevention, and control of plague in Qinghai Plateau.
PMID- 29939995
TI - The impact of temporal sampling resolution on parameter inference for biological
transport models.
AB - Imaging data has become an essential tool to explore key biological questions at
various scales, for example the motile behaviour of bacteria or the transport of
mRNA, and it has the potential to transform our understanding of important
transport mechanisms. Often these imaging studies require us to compare
biological species or mutants, and to do this we need to quantitatively
characterise their behaviour. Mathematical models offer a quantitative
description of a system that enables us to perform this comparison, but to relate
mechanistic mathematical models to imaging data, we need to estimate their
parameters. In this work we study how collecting data at different temporal
resolutions impacts our ability to infer parameters of biological transport
models by performing exact inference for simple velocity jump process models in a
Bayesian framework. The question of how best to choose the frequency with which
data is collected is prominent in a host of studies because the majority of
imaging technologies place constraints on the frequency with which images can be
taken, and the discrete nature of observations can introduce errors into
parameter estimates. In this work, we mitigate such errors by formulating the
velocity jump process model within a hidden states framework. This allows us to
obtain estimates of the reorientation rate and noise amplitude for noisy
observations of a simple velocity jump process. We demonstrate the sensitivity of
these estimates to temporal variations in the sampling resolution and extent of
measurement noise. We use our methodology to provide experimental guidelines for
researchers aiming to characterise motile behaviour that can be described by a
velocity jump process. In particular, we consider how experimental constraints
resulting in a trade-off between temporal sampling resolution and observation
noise may affect parameter estimates. Finally, we demonstrate the robustness of
our methodology to model misspecification, and then apply our inference framework
to a dataset that was generated with the aim of understanding the localization of
RNA-protein complexes.
PMID- 29939996
TI - Trends in corneal transplantation at the University Eye Hospital in Tubingen,
Germany over the last 12 years: 2004 - 2015.
AB - PURPOSE: This study aimed to investigate the trends in the surgical methods and
leading indications for corneal transplantations carried out over the last 12
years. METHODS: The data from the corneal graft waiting list and from all
keratoplasties carried out between 2004 and 2015 at the University Eye Hospital
in Tubingen were retrospectively analyzed. RESULTS: A total of 1,185
keratoplasties were performed between 2004 and 2015 at this hospital. The most
common surgical indications for corneal transplantation were Fuchs' endothelial
corneal dystrophy (35.2%) and keratoconus (18.9%) with keratoconus being the
leading cause during early years (from 2004 to 2009) and Fuch's dystrophy being
the leading cause from 2010 to 2015. Overall, the total count of performed
keratoplasties increased, from 385 corneal transplantations during the first 6
year period to 800 corneal transplantations during the second 6-year period (P =
0.008, using Mann-Whitney test). The Descemet's membrane endothelial keratoplasty
has become the favored surgical method for endothelial disorders with the number
of Descemet's membrane endothelial keratoplasties increasing significantly from
2008 to 2015. This increasing trend was statistically significant (P < 0.001
using multivariate adaptive regression splines (MARS). A decreasing trend was
also noted for the rate of penetrating keratoplasty since 2008 (P < 0.001 using
MARS). CONCLUSIONS: This research showed major changes in the preferred corneal
transplantation techniques and leading indications for keratoplasty over the last
12 years. More importantly, it seems that the rapid development and
implementation of endothelial keratoplasty, especially the Descemet's membrane
endothelial keratoplasty, has had a profound effect on and begun a new era in
corneal transplantation.
PMID- 29939997
TI - OFF-responses of interneurons optimize avoidance behaviors depending on stimulus
strength via electrical synapses.
AB - Optimization of the types and timing of avoidance behaviors depending on the
intensity of a noxious stimulus is essential for survival; however, processing in
the central nervous system and its developmental basis are largely unknown. Here,
we report that Caenorhabditis elegans preferentially selects one of three
different types of avoidance behaviors depending on the strength of the noxious
stimulus. We screened 210 neuronal transcription factors using a combination of
optogenetics and RNA interference methods and identified 19 candidates required
for avoidance behaviors. One candidate, gene lin-32 (abnormal cell LINeage 32),
which encodes an atonal homolog, is required for the neural fate determination of
AIB interneurons and functions by regulating the expression of electrical and
chemical synapse genes, namely, inx-1 (innexin 1) and AMPA-type ionotropic
glutamate receptor glr-1. When examined by Ca imaging, AIB showed an OFF calcium
increase to the noxious stimulus. The OFF calcium increase was provoked only by
strong stimulation, suggesting a role for optimization of the avoidance behavior.
However, lin-32 mutants showed an impaired AIB OFF calcium increase, concomitant
with a reduced occurrence of the dynamic avoidance behavior called the "omega
turn". The AIB neural responses may be transferred to downstream inter/motor
neurons projecting to the neck muscles via electrical synapses comprising inx-1.
Finally, we found a correlation between powerful contractions of the neck muscles
and omega turns. Thus, the central regulation of the magnitude and timing of
activation of the AIB interneurons optimizes the probability of omega turn
depending on the stimulus context.
PMID- 29939998
TI - Coding of self-motion-induced and self-independent visual motion in the rat
dorsomedial striatum.
AB - Evolutionary development of vision has provided us with the capacity to detect
moving objects. Concordant shifts of visual features suggest movements of the
observer, whereas discordant changes are more likely to be indicating
independently moving objects, such as predators or prey. Such distinction helps
us to focus attention, adapt our behavior, and adjust our motor patterns to meet
behavioral challenges. However, the neural basis of distinguishing self-induced
and self-independent visual motions is not clarified in unrestrained animals yet.
In this study, we investigated the presence and origin of motion-related visual
information in the striatum of rats, a hub of action selection and procedural
memory. We found that while almost half of the neurons in the dorsomedial
striatum are sensitive to visual motion congruent with locomotion (and that many
of them also code for spatial location), only a small subset of them are composed
of fast-firing interneurons that could also perceive self-independent visual
stimuli. These latter cells receive their visual input at least partially from
the secondary visual cortex (V2). This differential visual sensitivity may be an
important support in adjusting behavior to salient environmental events. It
emphasizes the importance of investigating visual motion perception in
unrestrained animals.
PMID- 29939999
TI - A high precision method for length-based separation of carbon nanotubes using bio
conjugation, SDS-PAGE and silver staining.
AB - Parametric separation of carbon nanotubes, especially based on their length is a
challenge for a number of nano-tech researchers. We demonstrate a method to
combine bio-conjugation, SDS-PAGE, and silver staining in order to separate
carbon nanotubes on the basis of length. Egg-white lysozyme, conjugated
covalently onto the single-walled carbon nanotubes surfaces using carbodiimide
method. The proposed conjugation of a biomolecule onto the carbon nanotubes
surfaces is a novel idea and a significant step forward for creating an indicator
for length-based carbon nanotubes separation. The conjugation step was followed
by SDS-PAGE and the nanotube fragments were precisely visualized using silver
staining. This high precision, inexpensive, rapid and simple separation method
obviates the need for centrifugation, additional chemical analyses, and expensive
spectroscopic techniques such as Raman spectroscopy to visualize carbon nanotube
bands. In this method, we measured the length of nanotubes using different image
analysis techniques which is based on a simplified hydrodynamic model. The method
has high precision and resolution and is effective in separating the nanotubes by
length which would be a valuable quality control tool for the manufacture of
carbon nanotubes of specific lengths in bulk quantities. To this end, we were
also able to measure the carbon nanotubes of different length, produced from
different sonication time intervals.
PMID- 29940000
TI - A cluster of cases of severe fever with thrombocytopenia syndrome bunyavirus
infection in China, 1996: A retrospective serological study.
AB - BACKGROUND: A cluster of eleven patients, including eight family members and
three healthcare workers with fever and thrombocytopenia occurred in Yixing
County, Jiangsu Province, China, from October to November 1996. However, the
initial investigation failed to identify its etiology. Severe fever with
thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS
bunyavirus (SFTSV), which was first discovered in 2009. The discovery of novel
SFTSV resulted in our consideration to test SFTSV on the remaining samples of
this cluster in September 2010. METHODOLOGY/PRINCIPAL FINDINGS: We
retrospectively analyzed the epidemiological and clinical data of this cluster.
The first case, one 55-year-old man with fulminant hemorrhagic diseases, died on
October 14, 1996. His younger brother (the second case) developed similar
hemorrhagic diseases after nursing him and then died on November 3. From November
4 to November 15, nine other patients, including six family members and three
medical staffs, developed fever and thrombocytopenia after exposure to the second
case. The sera of six patients were collected on November 24, 1996. IgM
antibodies against SFTSV were detected in all of the six patients' sera using
enzyme-linked immunosorbent assay (ELISA), while IgG antibodies were detected in
one patient's serum using an indirect immunofluorescence assay (IFA). We also
found that IgG antibodies against SFTSV were still detected in four surviving
patients' sera 14 years after illness onset. CONCLUSIONS AND SIGNIFICANCE: The
mysterious pathogen of the cluster in 1996 was proved to be SFTSV on the basis of
its epidemiological data, clinical data and serological results. It suggests that
SFTSV has been circulating in China for more than 10 years before being
identified in 2009, and SFTSV IgG antibodies can persist for up to 14 years.
PMID- 29940002
TI - Mental health effects caused by red imported fire ant attacks (Solenopsis
invicta).
AB - Susceptible individuals who have suffered painful stings caused by red imported
fire ants, Solenopsis invicta, usually experience physical health effects such as
fever, dizziness, generalized urticaria, or other systemic reactions such as
anaphylactic shock. Whether S. invicta stings also have negative effects on
mental health is not clear. In the present study, the psychological impact of S.
invicta stings was evaluated using a questionnaire that included a previously
published posttraumatic stress disorder (PTSD) checklist, the Patient Health
Questionnaire 9-item (PHQ-9), the Generalized Anxiety Disorder 7-item (GAD-7)
scale, the Beck Anxiety Inventory (BAI), and the Pittsburgh Sleep Quality Index,
5th scale (PSQI(5)). A total of 96 valid questionnaires were obtained; 37
participants were placed in the stung group, and 59 participants were placed in
the unstung group. Our results showed that symptoms of anxiety, depression and
sleep disturbances were not associated with S. invicta stings (for GAD-7 scale,
Pearson Chi-Square test, chi2 = 0.152, df = 1, P = 0.697; for the BAI, chi2 =
2.252, df = 1, P = 0.133; for the PHQ-9, chi2 = 0.098, df = 1, P = 0.754; for the
PSQI(5), chi2 = 0.536, df = 1, P = 0.453). In total, 2 of 83 individuals stung by
S. invicta met the criteria (>50) for PTSD. However, there was no significant
difference on PTSD between those stung by S. invicta in the 30-day group and the
over 30-day group (chi2 = 0.318, df = 1, P = 0.573). Overall, our data do not
show an effect of S. invicta stings on mental health as measured using a range of
indicators.
PMID- 29940001
TI - Functional annotation of hypothetical proteins from the Exiguobacterium
antarcticum strain B7 reveals proteins involved in adaptation to extreme
environments, including high arsenic resistance.
AB - Exiguobacterium antarcticum strain B7 is a psychrophilic Gram-positive bacterium
that possesses enzymes that can be used for several biotechnological
applications. However, many proteins from its genome are considered hypothetical
proteins (HPs). These functionally unknown proteins may indicate important
functions regarding the biological role of this bacterium, and the use of
bioinformatics tools can assist in the biological understanding of this organism
through functional annotation analysis. Thus, our study aimed to assign functions
to proteins previously described as HPs, present in the genome of E. antarcticum
B7. We used an extensive in silico workflow combining several bioinformatics
tools for function annotation, sub-cellular localization and physicochemical
characterization, three-dimensional structure determination, and protein-protein
interactions. This genome contains 2772 genes, of which 765 CDS were annotated as
HPs. The amino acid sequences of all HPs were submitted to our workflow and we
successfully attributed function to 132 HPs. We identified 11 proteins that play
important roles in the mechanisms of adaptation to adverse environments, such as
flagellar biosynthesis, biofilm formation, carotenoids biosynthesis, and others.
In addition, three predicted HPs are possibly related to arsenic tolerance.
Through an in vitro assay, we verified that E. antarcticum B7 can grow at high
concentrations of this metal. The approach used was important to precisely assign
function to proteins from diverse classes and to infer relationships with
proteins with functions already described in the literature. This approach aims
to produce a better understanding of the mechanism by which this bacterium adapts
to extreme environments and to the finding of targets with biotechnological
interest.
PMID- 29940003
TI - Co-fermentation of cellobiose and xylose by mixed culture of recombinant
Saccharomyces cerevisiae and kinetic modeling.
AB - Efficient conversion of cellulosic sugars in cellulosic hydrolysates is important
for economically viable production of biofuels from lignocellulosic biomass, but
the goal remains a critical challenge. The present study reports a new approach
for simultaneous fermentation of cellobiose and xylose by using the co-culture
consisting of recombinant Saccharomyces cerevisiae specialist strains. The co
culture system can provide competitive advantage of modularity compared to the
single culture system and can be tuned to deal with fluctuations in feedstock
composition to achieve robust and cost-effective biofuel production. This study
characterized fermentation kinetics of the recombinant cellobiose-consuming S.
cerevisiae strain EJ2, xylose-consuming S. cerevisiae strain SR8, and their co
culture. The motivation for kinetic modeling was to provide guidance and
prediction of using the co-culture system for simultaneous fermentation of mixed
sugars with adjustable biomass of each specialist strain under different
substrate concentrations. The kinetic model for the co-culture system was
developed based on the pure culture models and incorporated the effects of
product inhibition, initial substrate concentration and inoculum size. The model
simulations were validated by results from independent fermentation experiments
under different substrate conditions, and good agreement was found between model
predictions and experimental data from batch fermentation of cellobiose, xylose
and their mixtures. Additionally, with the guidance of model prediction,
simultaneous co-fermentation of 60 g/L cellobiose and 20 g/L xylose was achieved
with the initial cell densities of 0.45 g dry cell weight /L for EJ2 and 0.9 g
dry cell weight /L SR8. The results demonstrated that the kinetic modeling could
be used to guide the design and optimization of yeast co-culture conditions for
achieving simultaneous fermentation of cellobiose and xylose with improved
ethanol productivity, which is critically important for robust and efficient
renewable biofuel production from lignocellulosic biomass.
PMID- 29940004
TI - A bibliometric analysis of tuberculosis research, 2007-2016.
AB - BACKGROUND: Tuberculosis (TB) research is a key component of the End TB Strategy.
To track research output, we conducted a bibliometric analysis of TB research
from the past decade. METHODS: The Web of Science database was searched for
publications from January 2007 to December 2016 with "tuberculosis" in the title.
References were analysed using the R bibliometrix package. A year-stratified 5%
random subset was drawn to extract funding sources and identify research areas.
FINDINGS: The annual growth rate of publications was 7.3%, and was highest
(13.1%) among Brazil, Russia, India, China and South Africa (BRICS). The USA was
the most productive country, with 18.4% of references, followed by India (9.7%),
China (7.3%), England (6.5%), and South Africa (3.9%). In the subset analysis,
the most common research area was 'fundamental research' (33.8%). Frequently
acknowledged funders were US and EU-based, with China and India emerging as top
funders. Collaborations appeared more frequently between high-income countries
and low/medium income countries (LMICs), with fewer collaborations among LMICs.
CONCLUSION: The past decade has seen a continued increase in TB publications.
While USA continues to dominate research output and funding, BRICS countries have
emerged as major research producers and funders. Collaborations among BRICS would
enhance future TB research productivity.
PMID- 29940005
TI - The prevalence and potential fisheries consequences of Heterosporis sutherlandae
in a Minnesota lake.
AB - Heterosporis sutherlandae is an emerging microsporidian fish parasite in the
Great Lakes region. H. sutherlandae forms lesions in the muscle tissue of fishes
important to aquaculture and sport fishing. These lesions render the filet
inedible and may have fitness consequences. We evaluated the prevalence and
severity of H. sutherlandae among yellow perch (Perca flavescens) in a known
positive Minnesota lake, and used an equilibrium yield model to evaluate impacts
on harvest. Twenty-eight percent of the 400 yellow perch sampled were infected
with H. sutherlandae. Males were 1.5 times more likely to be infected than
females and were more severely infected. The presence of the parasite did not
vary with relative weight or age, but infection severity was highest among older
individuals that were in better condition. These results suggest that males are
more susceptible to infection, and that infection is not associated with maturity
or a gape-limiting food source. These results also suggest that heterosporosis
increases in severity with time or by increased exposure. Our equilibrium yield
model found that a 10% increase in mortality due to H. sutherlandae could result
in 30% and 10% reductions in yield and mean catch weight, respectively. The
results of this study direct future field sampling and laboratory experiments to
further understand and predict the impacts of this parasite.
PMID- 29940006
TI - Light quality characterization under climate screens and shade nets for
controlled-environment agriculture.
AB - Climate screens are typically used inside glass greenhouses to improve control of
humidity and temperature, and thus reduce energy expenditure. Shade nets are more
appropriate to use, either with or without polyethylene cladding, at locations
less-reliant on climate control, but where protection against hail, wind and
excessive solar radiation might be needed. In addition, insect screens and nets
can be employed to hinder insect pests and other invertebrates entering either
type of production environment, and to keep invertebrates used in pest management
contained inside. Screens and nets both transmit sunlight in a wavelength
specific manner, giving them the potential to affect plant morphology and
physiology. Screens and nets of various colours and nominal shading factors have
been described and studied; however, detailed measurements of their spectral
characteristics are scarce. We measured solar spectral photon-irradiance and its
attenuation by climate screens, shade nets, insect nets, greenhouse glass, and
polyethylene covers. Our aim was to elucidate the effects of different patterns,
colours, and shading factors, on light quality in production environments. Our
measurements reveal that there are large differences both in the fraction of
global irradiance attenuated and spectral ratios received under materials that
are otherwise superficially similar in terms of their appearance and texture. We
suggest that the type of spectral characterization that we performed is required
to fully interpret the results of research examining plant responses to different
types of screen and net. These data on spectral irradiance would benefit material
manufacturers, researchers, growers, and horticultural consultants, enabling
material selection to better match the solutions sought by growers and their
desired outcomes regarding plant performance.
PMID- 29940007
TI - Food anticipatory activity on a calorie-restricted diet is independent of Sirt1.
AB - A number of studies have demonstrated that the Sirtuin family member, Sirt1, is a
key integrator of growth, metabolism, and lifespan. Sirt1 directly interacts with
and deacetylates key regulators of the circadian clock, positioning it to be an
important link between feeding and circadian rhythms. In fact, one study suggests
that Sirt1 is necessary for behavioral anticipation of limited daily food
availability, a circadian process termed food anticipatory activity (FAA). In
their study, mice overexpressing Sirt1 had enhanced FAA, while mice lacking Sirt1
had little to no FAA. Based on the supposition that Sirt1 was indeed required for
FAA, we sought to use Sirt1 deletion to map the neural circuitry responsible for
FAA. We began by inactivating Sirt1 using the cell-type specific Cre-driver lines
proopiomelanocortin, but after observing no effect on body weight loss or FAA we
then moved on to more broadly neuronal Cre drivers Ca2+/calmodulin-dependent
protein kinase II and nestin. As neither of these neuronal deletions of Sirt1 had
impaired FAA, we then tested 1) a broad postnatal tamoxifen-inducible deletion,
2) a complete, developmental knockout of Sirt1, and 3) a gene replacement,
catalytically inactive, form of Sirt1; but all of these mice had FAA similar to
controls. Therefore, our findings suggest that FAA is completely independent of
Sirt1.
PMID- 29940008
TI - A geometric model for the human pulmonary valve in its fully open case.
AB - The human pulmonary valve, one of the key cardiac structures, plays an important
role in circulatory system. However, there are few mathematical models to
accurately simulate it. In this paper, we establish a geometric model of the
normal human pulmonary valve from a mathematical perspective in the fully opening
case. Based on the statistical data of the human pulmonary valves, we assume that
the motions of the three cusps are symmetrical in the cardiac cycle. Thus, we
first propose that each cusp is a part of the cylindrical shell according to its
structure and physiological feature. The parameters for the pulmonary valve cusps
in three-dimensional space are obtained by the fitting functions. We verify the
accuracy of our results by comparing the areas of the pulmonary valve and
pulmonary valve flap.
PMID- 29940009
TI - Assessment of the biological quality of port areas: A case study on the three
harbours of La Rochelle: The marina, the fishing harbour and the seaport.
AB - This work was designed to investigate biological impacts at 3 dates (day 0, day 7
and day 21) on black scallops (Mimachlamys varia) in the three ports areas of La
Rochelle town in winter 2017. In order to assess the biological effects on the
wild population of black scallops, bivalves were place in four different
locations: in the three ports (semi-closed areas), and in a marshland
uncontaminated site (closed area). Biomarkers of effects (heavy metals) and
exposure (oxidative stress and immunological effects) were assessed in the
digestive glands of specimens in order to compare two techniques of sampling:
"pool" technique and "inter-subject" technique. Our findings reported in the both
techniques show significant modulation of GST (detoxification), SOD (antioxidant
response) and MDA (lipid peroxidation) in bivalves exposed to a specific
contamination in each port. Laccase-type enzyme also highlighted an important
aspect in terms of biomarker response of the immune function at the 7th day of
exposition. Overall, our study demonstrated that the "pool" technique using the
same quality indicator M. varia could be used to obtain reliable results at lower
costs. In contrast, in fundamental context, the "inter-subject" technique could
bring more precise results to light. However, it requires burdensome and costly
handling.
PMID- 29940010
TI - Validation of a new study skills scale to provide an explanation for depressive
symptoms among medical students.
AB - BACKGROUND: Medical students are faced with enormous academic demands that may
influence their emotional wellbeing. The high rate of depression among medical
students and its negative impact is an impetus to find explanation for the
factors associated with it. Study skills that students possess might be such a
factor. The current tools for the assessment of the study skills may have certain
limitations, particularly for different cultural settings. OBJECTIVES: This study
aimed to develop and validate a Study Skills Inventory (SSI), and to investigate
the relationship between the students' study skills and the extent (severity) of
depressive symptoms, measured using the validated tool. METHOD: The first version
of the SSI was developed through expert consensus. The inventory was then
administered to a randomly selected group of medical students. Confirmatory
factor analysis was conducted for the internal validity. External validation was
conducted by comparing the results of the SSI with the "Approaches and Study
Skills Inventory for Students" (ASSIST). After validation, the correlation
between the SSI total score with the Beck Depression Inventory II (BDI-II) total
score was investigated using the Pearson correlation coefficient. The means of
the total study skills scores for each severity category of depression were
compared using ANOVA. RESULTS: A total of 23 items, representing five sub-scales,
were included in the inventory. Based on 372 student responses (response rate of
93%), the five-factor solution explained a cumulative variance of 52% and Cronach
alpha was 0.84. The SSI total score had a significant negative association with
the BDI-II depression score (Pearson correlation of -.348** and P<0.0001).
CONCLUSION: This study showed evidence for acceptable reliability and validity of
the newly developed SSI. Poor study skills were found to correlate with higher
depressive symptoms. This association needs confirmation in future research and
could open a new door for better understanding of student depression.
PMID- 29940011
TI - Current inventory and changes of the input/output balance of trace elements in
farmland across China.
AB - The inventory and input/output balance of trace elements in farmland play an
important role in risk assessment and soil management, but there is little
information about nationwide changes of the input/output balance of trace
elements in farmland in China. In the present study, the inventory of trace
element inputs to farmland was updated based on the dataset from the literature
published during 2006-2015, and changes of the input/output balance were
investigated. Compared with 1999-2006, net inputs of Cr, Ni, and Zn increased by
52.9%, 59.7%, and 20.6%, respectively. The increases in fossil fuel derived
energy consumption, industrial manufacture, municipal solid waste incineration,
and transportation were the predominant contributors to these increases. Net
inputs of Cd, Cu, and Hg decreased dramatically by 46.7%, 25.2%, and 50.4%,
respectively. The decreases are due to the strict management of feed additives,
fertilizers, and emissions of atmospheric pollutants. Net inputs of As and Pb
still remained relatively stable. These results demonstrated that better
achievements have been gained by administration of air, water and soil in China.
Regulation of atmospheric emission for Cr, Ni, and Zn was recommended as
atmospheric deposition was the predominant source for increases of Cr, Ni, and Zn
inputs to farmland across China.
PMID- 29940012
TI - Performance of the National Tuberculosis Control Program in the post conflict
Liberia.
AB - BACKGROUND: Tuberculosis is a major public health problem in Liberia. According
to the World Health Organization (WHO), the incidence of tuberculosis in Liberia
is significantly increasing from year to year. However, little is known about the
performance of the programme and the challenges after the 14 years of civil war
which ended in 2003.The purpose of the study was to evaluate the performance of
the TB programme of Liberia. METHODS: The study utilised mixed research design;
both quantitative and qualitative methods were used in this study conducted from
2013 to 2014. For the quantitative part of the study, a questionnaire, laboratory
performance and eleven years TB programme data (2003-2013) were used. For the
performance of tuberculosis laboratory testing, all the 107 functional
tuberculosis microscopy centers in Liberia were included. For the qualitative
part of the study, an interview of 10 informants and two focus group discussions
(FGDs) were also conducted, each comprising of eight people. Themes and subthemes
emerged from the two FGDs. Data was analysed in line with the Donabedian model.
Quantitative findings were analysed and presented using both descriptive and
inferential statistics. RESULTS: The study findings pointed out that there was
overall improvement in the performance of the tuberculosis control programme in
Liberia from 2003 to 2013. The percentage of cured patients was 60% in 2005 and
62% in 2013. Percentage of treatment completed was 16% in 2005 and 21% in 2013.
The case detection rate was 57% and treatment success rate 80% in 2013. The
default rate was 11% in 2013. Of the 139 participants, 120 (86%) completed TB
treatment while 19 (14%) did not. CONCLUSION: Between 2003 and 2013, the National
Leprosy and Tuberculosis Control Programme (NLTCP) succeeded in restoring the TB
services and improving some of the TB treatment outcomes including the Directly
observed treatment short courses(DOTS) coverage. Despite these improvements, the
TB treatment, laboratory services and human resource capacity lagged behind. The
TB programme of Liberia needs to develop new strategies to address its
challenges.
PMID- 29940013
TI - Plasma adiponectin levels are associated with circulating inflammatory cytokines
in autoantibody positive first-degree relatives of rheumatoid arthritis patients.
AB - BACKGROUND: Extra-articular manifestations of rheumatoid arthritis (RA),
potentially due to systemic inflammation, include cardiovascular disease and
sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated
in inflammatory processes in RA, but little is known regarding its association
with inflammation in a pre-clinical period. Therefore, we investigated whether
adiponectin was associated with inflammatory markers in individuals at risk for
RA, and whether RA-related autoimmunity modifies these associations. METHODS: We
analyzed samples from 144 first-degree relatives (FDRs) of RA probands, of whom
23 were positive for anti-cyclic citrullinated peptide antibody and/or >= 2
rheumatoid factor isotypes (IgM, IgG or IgA). We called this phenotype the 'high
risk autoantibody profile (HRP)' as it has been shown in prior work to be >96%
specific for future RA. We measured adiponectin, cytokines, and high-sensitivity
C-reactive protein (hsCRP). Using linear mixed effects models, we evaluated
interaction between HRP positivity and adiponectin on inflammatory markers,
adjusting for age, sex, ethnicity, body mass index, pack-years smoking, and use
of cholesterol-lowering medications. RESULTS: In everyone, adiponectin
concentration was inversely associated with hsCRP and IL-1beta in adjusted
models, where a 1% higher adiponectin was associated with a 26% lower hsCRP (p =
0.04) and a 26% lower IL-1beta (p = 0.04). Significant interactions between HRP
and adiponectin for associations with GM-CSF, IL-6, and IL-9 were detected in
fully adjusted models (p = 0.0006, p = 0.006, p = 0.01, respectively). In HRP
positive FDRs but not HRP negative FDRs, a 1% higher adiponectin was associated
with 97% higher GM-CSF, 73% higher IL-6, and 54% higher IL-9 concentrations.
CONCLUSIONS: Adiponectin associates with inflammatory markers, and these
associations differ in individuals with a high-risk autoantibody profile compared
with those without. The interaction between adiponectin and autoimmunity warrants
further investigation into the potential systemic effects of RA-related
autoantibodies and adiponectin on inflammation in the absence of clinically
apparent RA.
PMID- 29940014
TI - Coexpression network and phenotypic analysis identify metabolic pathways
associated with the effect of warming on grain yield components in wheat.
AB - Wheat grains are an important source of human food but current production amounts
cannot meet world needs. Environmental conditions such as high temperature (above
30 degrees C) could affect wheat production negatively. Plants from two wheat
genotypes have been subjected to two growth temperature regimes. One set has been
grown at an optimum daily mean temperature of 19 degrees C while the second set
of plants has been subjected to warming at 27 degrees C from two to 13 days after
anthesis (daa). While warming did not affect mean grain number per spike, it
significantly reduced other yield-related indicators such as grain width, length,
volume and maximal cell numbers in the endosperm. Whole genome expression
analysis identified 6,258 and 5,220 genes, respectively, whose expression was
affected by temperature in the two genotypes. Co-expression analysis using WGCNA
(Weighted Gene Coexpression Network Analysis) uncovered modules (groups of co
expressed genes) associated with agronomic traits. In particular, modules
enriched in genes related to nutrient reservoir and endopeptidase inhibitor
activities were found to be positively associated with cell numbers in the
endosperm. A hypothetical model pertaining to the effects of warming on gene
expression and growth in wheat grain is proposed. Under moderately high
temperature conditions, network analyses suggest a negative effect of the
expression of genes related to seed storage proteins and starch biosynthesis on
the grain size in wheat.
PMID- 29940015
TI - Antioxidant metabolism variation associated with alkali-salt tolerance in thirty
switchgrass (Panicum virgatum) lines.
AB - Soil salinization is a major factor limiting crop growth and development in many
areas. Switchgrass (Panicum virgatum L.) is an important warm-season grass
species used for biofuel production. The objective of this study was to
investigate antioxidant metabolism, proline,and protein variation associated with
alkali-salt tolerance among 30 switchgrass lines and identify metabolic markers
for evaluating alkali-salt tolerance of switchgrass lines. The grass lines were
transplanted into plastic pots containing fine sand. When the plants reached E5
developmental stage, they were subjected to either alkali-salt stress treatment
(150 mM Na+ and pH of 9.5) or control (no alkali-salt stress) for 20 d. The 30
switchgrass lines differed in alkali-salt tolerance as determined by the level of
leaf malondialdehyde (MDA), antioxidant enzyme activity [(superoxide dismutase
(SOD), catalase (CAT), ascorbate peroxidase (APX)], proline and protein. Alkali
salt stress increased MDA, proline, SOD, reduced CAT activity, but its effect on
protein and APX varied depending on lines. Wide variations in the five parameters
existed among the 30 lines. In general, the lines with higher CAT activity and
lower proline content under alkali-salt stress had less MDA, exhibiting better
alkali-salt tolerance. Among the five parameters, CAT can be considered as
valuable metabolic markers for assessment of switchgrass tolerance to alkali-salt
stress.
PMID- 29940016
TI - Caspase recruitment domain-containing protein 9 (CARD9) knockout reduces regional
ischemia/reperfusion injury through an attenuated inflammatory response.
AB - Ischemic heart disease remains a leading cause of morbidity and mortality in the
United States. Interventional reperfusion induces further damage to the ischemic
myocardium through neutrophil infiltration and acute inflammation. As caspase
recruitment domain-containing protein 9 (CARD9) plays a critical role in innate
immune response and inflammation, we hypothesized that CARD9 knockout would
provide protection against ischemia and reperfusion (I/R) injury through
attenuation of acute inflammatory responses. C57BL/6 wild-type (WT) and CARD9-/-
mice were subjected to 45 min left anterior descending (LAD) coronary artery
occlusion followed by 24-h reperfusion. Area at risk (AAR) and infarct size were
measured by Evans blue and triphenyltetrazolium chloride (TTC) staining. Frozen
heart sections were stained with anti-mouse GR-1 antibody to detect infiltrated
neutrophils. Concentrations of cytokines/chemokines TNF-alpha, IL-6, CXCL-1 and
MCP-1 were determined in heart tissue homogenate and serum by ELISA assay.
Western immunoblotting analyses were performed to measure the phosphorylation of
p38 MAPK. Our results indicate that following I/R, infarct size was significantly
smaller in CARD9-/- mice compared to WT. The number of infiltrated neutrophils
was significantly lower in CARD9-/- mice compared to WT. Levels of TNF-alpha, IL
6, CXCL-1 and MCP-1 were significantly reduced in heart tissue and serum from
CARD9-/- mice compared to WT. CARD9-/- mice also exhibited significantly lower
levels of phosphorylated p38 MAPK. Taken together, our results suggest that CARD9
knockout protects the heart from ischemia/reperfusion (I/R) injury, possibly
through reduction of neutrophil infiltration and attenuation of CARD9-associated
acute inflammatory signaling.
PMID- 29940017
TI - Association of cerebral oxygenation with estimated glomerular filtration rate and
cognitive function in chronic kidney disease patients without dialysis therapy.
AB - BACKGROUND: A decline in estimated glomerular filtration rate (eGFR) is
reportedly associated with increased prevalence rates of cognitive impairment.
However, data concerning the association between the cerebral saturation of
oxygen (rSO2) and cognitive function of patients with chronic kidney disease
(CKD) is limited. This study aimed to (i) elucidate the clinical factors
associating with cerebral rSO2 and (ii) investigate the association between
cerebral rSO2 and cognitive assessment in CKD patients. METHODS: A total of 40
CKD patients not requiring dialysis (26 men and 14 women; mean age, 61.0 +/- 2.7
years) were recruited. The numbers of patients at each CKD stage were as follows:
G1, 5; G2, 8; G3a, 6; G3b, 5; G4, 11; and G5, 5. Cerebral rSO2 was monitored at
the forehead using the oxygen saturation monitor INVOS 5100C. The cognitive
function of each patient was confirmed using the Mini-Mental State Examination
(MMSE). RESULTS: Cerebral rSO2 levels were significantly higher in CKD patients
than in hemodialysis patients (63.8 +/- 1.5% vs. 44.9 +/- 2.2%, p < 0.001).
Multiple regression analysis showed that cerebral rSO2 was independently
associated with eGFR (standardized coefficient: 0.530), serum albumin
concentration (standardized coefficient: 0.365), and serum sodium concentration
(standardized coefficient: 0.224). Furthermore, MMSE showed a significantly
positive correlation with cerebral rSO2 (r = 0.624, p < 0.001). CONCLUSIONS:
Cerebral rSO2 was affected by eGFR and serum albumin and sodium concentrations in
CKD patients. Furthermore, cerebral rSO2 monitoring, which reflected MMSE scores,
might be a useful method for assessing cognitive function in CKD patients.
PMID- 29940018
TI - Comparison of 3D printed prostate models with standard radiological information
to aid understanding of the precise location of prostate cancer: A construct
validation study.
AB - BACKGROUND: To investigate the reliability with which healthcare professionals
with different levels of expertise are able to impart the exact location of
prostate cancer (PCA) after (A) reading written magnetic resonance imaging (MRI)
reports, (B) attending MRI presentations in multidisciplinary team meetings
(MDT), and (C) examining 3D printed prostate models, which represents a new
technology to describe the location of PCA lesions. METHODS: We used three
different PCA cases to assess the three information tools. Construct validation
was performed using two healthcare groups with different levels of expertise: (1)
Nine expert urologists in PCA, and (2) nine medical students. After each
information tool, the study participants plotted the tumor location in a 2
dimensional prostate diagram. A scoring system was established to evaluate the
drawings in terms of accuracy of plotting tumor position. Data are shown as
median scores with interquartile range. RESULTS: Within the expert group, no
significant difference was seen in the overall scoring results between the
information tools (p = 0.34). Medical students performed significantly worse with
MDT information (p = 0.03). Experts performed better in all three information
tools compared to students, resulting in a significantly 25% higher overall total
score (25.0[22.3-26.7] vs. 20.0[15.0-24.0], p<0.001). The difference was largest
after MDT information, with experts showing a 49% better scoring (p<0.001), and
second largest with the 3D printed models, showing a 17% better scoring of the
experts (p = 0.07). No difference was found in the written MRI report scoring
results between experts and students. CONCLUSIONS: 3D printed models provided
better orientation guide to medical students compared to MDT MRI presentations.
This indicates that the 3D printed models might be easier to understand than the
current gold standard MDT conferences. Therefore, 3D models may play an
increasingly important role in providing guidance for orientation for less
experienced individuals, such as surgical trainees.
PMID- 29940019
TI - Haploid selection, sex ratio bias, and transitions between sex-determining
systems.
AB - Sex determination is remarkably dynamic; many taxa display shifts in the location
of sex-determining loci or the evolution of entirely new sex-determining systems.
Predominant theories for why we observe such transitions generally conclude that
novel sex-determining systems are favoured by selection if they equalise the sex
ratio or increase linkage with a locus that experiences different selection in
males versus females. We use population genetic models to extend these theories
in two ways: (1) We consider the dynamics of loci very tightly linked to the
ancestral sex-determining loci, e.g., within the nonrecombining region of the
ancestral sex chromosomes. Variation at such loci can favour the spread of new
sex-determining systems in which the heterogametic sex changes (XY to ZW or ZW to
XY) and the new sex-determining region is less closely linked (or even unlinked)
to the locus under selection. (2) We consider selection upon haploid genotypes
either during gametic competition (e.g., pollen competition) or meiosis (i.e.,
nonmendelian segregation), which can cause the zygotic sex ratio to become
biased. Haploid selection can drive transitions between sex-determining systems
without requiring selection to act differently in diploid males versus females.
With haploid selection, we find that transitions between male and female
heterogamety can evolve so that linkage with the sex-determining locus is either
strengthened or weakened. Furthermore, we find that sex ratio biases may increase
or decrease with the spread of new sex chromosomes, which implies that
transitions between sex-determining systems cannot be simply predicted by
selection to equalise the sex ratio. In fact, under many conditions, we find that
transitions in sex determination are favoured equally strongly in cases in which
the sex ratio bias increases or decreases. Overall, our models predict that sex
determination systems should be highly dynamic, particularly when haploid
selection is present, consistent with the evolutionary lability of this trait in
many taxa.
PMID- 29940020
TI - Self-reports from behind the scenes: Questionable research practices and rates of
replication in ego depletion research.
AB - The strength model of self-control is one of the most influential and well
established models of self-regulation in social psychology. However, recent
attempts to replicate the ego depletion effect have sometimes failed. The goal of
this study is to investigate self-reported replication rates and the frequency of
a set of questionable research practices (QRP) in ego depletion research. A
literature search resulted in 1721 researchers who had previously published on
ego depletion. They were invited to participate in an anonymous online survey.
The respondents (n = 277), on average, had published over three papers on ego
depletion, and had completed more than two additional, unpublished studies.
Respondents indicated that in more than 40% of their studies, results were
similar in magnitude to those reported in the existing literature, and more than
60% reported conducting a priori power analyses. 39.2% of respondents were aware
of other researchers who engaged in the surveyed QRP's, while 37.7% affirmed to
have employed said QRP's. These results underline the importance of reducing
QRP's to reliably test the validity of the ego depletion effect.
PMID- 29940021
TI - Intermediate frequency of aversive conditioning best restores wariness in
habituated elk (Cervus canadensis).
AB - In protected areas around the world, wildlife habituate to humans and human
infrastructure, potentially resulting in human-wildlife conflict, and leading to
trophic disruptions through excess herbivory and disconnection of predators from
prey. For large species that threaten human safety, wildlife managers sometimes
attempt to reverse habituation with aversive conditioning. This technique
associates people as a conditioned stimulus with a negative, unconditioned
stimulus, such as pain or fright, to increase wariness and prevent the need for
lethal wildlife management. Resistance to aversive conditioning by some
habituated individuals often results in more frequent conditioning events by
managers, but there are few studies of conditioning frequency with which to
evaluate the usefulness of this management response. We evaluated the effect of
conditioning frequency on the wariness of elk (Cervus canadensis) by subjecting
marked individuals to predator-resembling chases by people over a period of three
months. In that time, animals were subjected to conditioning a total of 3, 4, 5,
6, 7, or 9 times which we analyzed as both an ordinal variable and a binary one
divided into low (3-5) and high (6-9) conditioning frequencies. We measured
wariness before, during, and after the conditioning period using flight response
distances from an approaching researcher. During the conditioning period, overall
wariness increased significantly for elk in both treatment groups, although the
increase was significantly greater in individuals subjected to high conditioning
frequencies. However in the post-conditioning period, wariness gains also
declined most in the high-frequency group, equating to more rapid extinction of
learned behaviour. Across all treatment frequencies, rapid changes in flight
responses also characterized the individuals with the lowest wariness at the
beginning of the study period, suggesting that individuals with greater
behavioural flexibility are more likely to habituate to both people and their
attempts to change wariness via aversive conditioning. Together, our results
imply that aversive conditioning may be most effective at intermediate
frequencies and that its utility might be further increased with proactive
assessment of individual personalities in habituated wildlife.
PMID- 29940022
TI - Effects of phthalates on normal human breast cells co-cultured with different
fibroblasts.
AB - Whether or not phthalates play a role in breast carcinogenesis remains to be
determined. The goal of this study was to explore the effects of phthalates on
the growth of normal MCF-10A breast cells modulated by breast fibroblasts.
Fibroblasts were derived from normal mammary tissue adjacent to both estrogen
receptor (ER) positive and negative primary breast cancers, which were grown
separately from nontumorigenic MCF-10A epithelial cells. MCF-10A co-culture cells
were treated with 10 nM 17beta-estradiol (E2), Butyl benzyl phthalate (BBP), di(n
butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP) (10 and 100 nM).
After incubation for 120 hours, the cells were harvested and extracted for MTT
assay. Western blot analysis was used to evaluate the proliferative pathway
proteins and the effects on ER alpha. Only fibroblasts from ER (+) breast cancer
significantly stimulated proliferation of MCF-10A cells. Exposure of the co
culture to E2, BBP, DBP, DEHP, and E2 combined with one of these phthalates
resulted in significantly increased cell proliferation, as well as proliferating
cell nuclear antigen (PCNA) and ER alpha expressions. The present study
demonstrates that phthalates express a significant influence in fibroblast
epithelial interactions, similarly to the effects of E2 on breast cells. The
effects of phthalates on normal breast cells depend upon ER modulating actions.
In breast carcinogenesis, phthalates should be considered as having endocrine
disrupting potential, even at low concentrations.
PMID- 29940023
TI - Genetic diversity and population structure of African village dogs based on
microsatellite and immunity-related molecular markers.
AB - The village and street dogs represent a unique model of canine populations. In
the absence of selective breeding and veterinary care, they are subject mostly to
natural selection. Their analyses contribute to understanding general mechanisms
governing the genetic diversity, evolution and adaptation. In this study, we
analyzed the genetic diversity and population structure of African village dogs
living in villages in three different geographical areas in Northern Kenya. Data
obtained for neutral microsatellite molecular markers were compared with those
computed for potentially non-neutral markers of candidate immunity-related genes.
The neutral genetic diversity was similar to other comparable village dog
populations studied so far. The overall genetic diversity in microsatellites was
higher than the diversity of European pure breeds, but it was similar to the
range of diversity observed in a group composed of many European breeds,
indicating that the African population has maintained a large proportion of the
genetic diversity of the canine species as a whole. Microsatellite marker
diversity indicated that the entire population is subdivided into three
genetically distinct, although closely related subpopulations. This genetical
partitioning corresponded to their geographical separation and the observed gene
flow well correlated with the communication patterns among the three localities.
In contrast to neutral microsatellites, the genetic diversity in immunity-related
candidate SNP markers was similar across all three subpopulations and to the
European group. It seems that the genetic structure of this particular population
of Kenyan village dogs is mostly determined by geographical and anthropogenic
factors influencing the gene flow between various subpopulations rather than by
biological factors, such as genetic contribution of original migrating
populations and/or the pathogen-mediated selection. On the other hand, the study
of oldest surviving dogs suggested a biological mechanism, i.e. a possible
advantage of the overal heterozygosity marked by the the microsatellite loci
analyzed.
PMID- 29940025
TI - The burden of out of pocket costs and medical debt faced by households with
chronic health conditions in the United States.
AB - INTRODUCTION: To examine the relationship between chronic health conditions and
out-of-pocket costs (OOPC) and medical debt. METHODS: Secondary data from the
2013 Panel Study of Income Dynamics (PSID) was used. Households whose head of
household and spouse (for married households) were 18 to 64 years old were
included. RESULTS: Households with 1 to 3 chronic conditions had higher odds of
having any OOPC compared to households with no chronic conditions (AOR 1.74, 95%
CI 1.39, 2.17) (p < .01). Households with 1 to 3 and 4 or more chronic health
conditions were associated with higher odds of having any medical debt (AOR 2.24,
95% CI 1.75 to 2.87; AOR 5.04, 95% CI 3.04 to 8.34) compared to those with no
chronic conditions (p < 0.01). Similarly, 1 to 3 and 4 or more chronic health
conditions was associated with higher amounts of OOPC (Exponentiated Coefficient
1.18, 95% CI 1.03 to 1.36; Exponentiated Coefficient 1.56, 95% CI 1.17 to 2.07)
and medical debt (Exponentiated Coefficient 1.69, 95% CI 1.23 to 2.34;
Exponentiated Coefficient 2.73, 95% CI 1.19 to 6.25) compared to households with
no chronic conditions (p < 0.05). CONCLUSIONS: Findings from this study show that
the presence of chronic health conditions impose a large financial burden on some
households.
PMID- 29940024
TI - Role of mucosal high-risk human papillomavirus types in head and neck cancers in
Romania.
AB - BACKGROUND: Limited information is available about the involvement of human
papillomavirus (HPV) in head and neck squamous cell carcinomas (HNSCCs) in
Romanian patients. OBJECTIVE: To evaluate the HPV-attributable fraction in HNSCCs
collected in Northeastern Romania. MATERIALS AND METHODS: In total, 189 formalin
fixed paraffin-embedded tissue samples (99 oral cavity tumors, 28 oropharynx, 48
pharynx, and 14 larynx/hypopharynx) were analyzed for HPV DNA and RNA using
Luminex-based assays, and for overexpression of p16INK4a (p16) by
immunohistochemistry. RESULTS: Of the 189 cases, 23 (12.2%) were HPV DNA
positive, comprising half of the oropharyngeal cases (14/28, 50.0%) and 9/161
(5.6%) of the non-oropharyngeal cases. HPV16 was the most prevalent HPV type
(20/23, 86.9%), followed by HPV18 (5/23, 21.7%) and HPV39 (1/23, 4.3%). Only two
(2/189, 1.1%) HNSCC cases were HPV-driven, i.e. positive for both HPV DNA and
RNA. CONCLUSION: A very small subset of HNSCC cases within this cohort from
Northeastern Romania appeared to be HPV-driven.
PMID- 29940027
TI - The trade-off between graduate student research and teaching: A myth?
AB - Many current faculty believe that teaching effort and research success are
inversely correlated. This trade-off has rarely been empirically tested; yet, it
still impedes efforts to increase the use of evidence-based teaching (EBT), and
implement effective teaching training programs for graduate students, our future
faculty. We tested this tradeoff for graduate students using a national sample of
life science PhD students. We characterize how increased training in EBT impacts
PhD students' confidence in their preparation for a research career, in
communicating their research, and their publication number. PhD students who
invested time into EBT did not suffer in confidence in research preparedness,
scientific research communication, or in publication number. Instead, overall,
the data trend towards a slight synergy between investing in EBT and research
preparation. Thus, the tension between developing research and teaching skills
may not be salient for today's graduate students. This work is proof of concept
that institutions can incorporate training in EBT into graduate programs without
reducing students' preparedness for a research career. Although some institutions
already have graduate teaching programs, increasing these programs at scale, and
including training in EBT methods could create a new avenue for accelerating the
spread of evidence-based teaching and improved teaching across higher education.
PMID- 29940026
TI - Health-related quality of life in intensive care survivors: Associations with
social support, comorbidity, and pain interference.
AB - BACKGROUND: Experiences during a stay in the intensive care unit (ICU), including
pain, delirium, physical deterioration, and the critical illness itself, may all
influence survivors' health-related quality of life (HRQOL). However, few studies
have examined the influence of social support, comorbidity, and pain interference
on ICU survivors' HRQOL. OBJECTIVES: To investigate possible associations between
social support, number of comorbidities, and pain interference on HRQOL in ICU
survivors. METHODS: ICU survivors responded to a survey 3 months (n = 118) and 1
year (n = 89) after ICU discharge. HRQOL was measured using the Short Form Health
Survey-12 (v1), social support using the revised Social Provision Scale, pain
interference using the Brief Pain Inventory-Short Form, and comorbidities using
the Self-Administered Comorbidity Questionnaire. RESULTS: Physical and mental
HRQOL were reduced at both 3 months and 1 year in ICU survivors compared with the
general population. This reduction was more pronounced at 3 months for physical
HRQOL, while a small reduction in mental HRQOL was not clinically relevant.
Social support was statistical significantly positively associated with mental
HRQOL at 3 months, while number of comorbidities was statistical significantly
associated with a reduction in physical HRQOL at 3 months and 1 year and mental
HRQOL at 1 year. Lastly pain interference was significantly associated with a
reduction in physical HRQOL at 3 months and 1 year. CONCLUSIONS: ICU survivors
primarily report reduced physical HRQOL. Social support was positively associated
with mental HRQOL, while number of comorbidities, and pain interference were all
significantly associated with a reduction in HRQOL. Pain interference was
associated with the largest reduction in HRQOL.
PMID- 29940028
TI - An optimized methodology for whole genome sequencing of RNA respiratory viruses
from nasopharyngeal aspirates.
AB - Over the last decade, the number of viral genome sequences deposited in available
databases has grown exponentially. However, sequencing methodology vary widely
and many published works have relied on viral enrichment by viral culture or
nucleic acid amplification with specific primers rather than through unbiased
techniques such as metagenomics. The genome of RNA viruses is highly variable and
these enrichment methodologies may be difficult to achieve or may bias the
results. In order to obtain genomic sequences of human respiratory syncytial
virus (HRSV) from positive nasopharyngeal aspirates diverse methodologies were
evaluated and compared. A total of 29 nearly complete and complete viral genomes
were obtained. The best performance was achieved with a DNase I treatment to the
RNA directly extracted from the nasopharyngeal aspirate (NPA), sequence
independent single-primer amplification (SISPA) and library preparation performed
with Nextera XT DNA Library Prep Kit with manual normalization. An average of
633,789 and 1,674,845 filtered reads per library were obtained with MiSeq and
NextSeq 500 platforms, respectively. The higher output of NextSeq 500 was
accompanied by the increasing of duplicated reads percentage generated during
SISPA (from an average of 1.5% duplicated viral reads in MiSeq to an average of
74% in NextSeq 500). HRSV genome recovery was not affected by the presence or
absence of duplicated reads but the computational demand during the analysis was
increased. Considering that only samples with viral load >= E+06 copies/ml NPA
were tested, no correlation between sample viral loads and number of total
filtered reads was observed, nor with the mapped viral reads. The HRSV genomes
showed a mean coverage of 98.46% with the best methodology. In addition, genomes
of human metapneumovirus (HMPV), human rhinovirus (HRV) and human parainfluenza
virus types 1-3 (HPIV1-3) were also obtained with the selected optimal
methodology.
PMID- 29940029
TI - Correction: Population-based study of chlamydial and gonococcal infections among
women in Shenzhen, China: Implications for programme planning.
AB - [This corrects the article DOI: 10.1371/journal.pone.0196516.].
PMID- 29940030
TI - Implementing mental health training programmes for non-mental health trained
professionals: A qualitative synthesis.
AB - INTRODUCTION: Given the prevalence of mental health problems globally, there is
an increasing need for the police and other non-mental health trained
professionals to identify and manage situations involving individuals with mental
health problems. The review aimed to identify and explore qualitative evidence on
views and experiences of non-mental health professionals receiving mental health
training and the barriers and facilitators to training delivery and
implementation. METHODS: A meta-synthesis of qualitative evidence on the
barriers, facilitators and perceived impact of mental health training programmes
for non-mental health trained professionals. Systematic literature searches were
undertaken of the following databases: Criminal Justice Abstracts (CJA); MEDLINE;
Embase; PsycINFO; ASSIA; CENTRAL; SSCI; ERIC; Campbell Library; Social Care
Online and EPOC from 1995 to 2016. Records were independently screened for
eligibility by two researchers, data extraction and quality appraisal of studies
was also undertaken independently by two researchers. The CASP tool was used to
quality appraise included studies. Included studies were synthesised using a meta
ethnographic approach as outlined by Noblit and Hare. RESULTS: 10,282 records
were identified and eight qualitative studies were included. A range of barriers
and facilitators to training were identified and related to the delivery and
content of training; the use of additional resources; and staff willingness to
engage with training and organisational factors. The perceived impact of training
was also discussed in terms of how it affects trainees; perceptions of mental
health; self-perception; responses to situations involving mental health and the
potential of training to reduce injury or physical harm in situations involving
mental health. The value of training and how to measure its impact were also
discussed. CONCLUSION: Findings from this review have implications for those
designing, implementing and evaluating mental health training programmes. It is
recommended that research evaluating mental health training includes a
qualitative component to ensure that the barriers and facilitators to training
and its impact on trainees' perceptions of mental health are understood. PROTOCOL
REGISTRATION NUMBER: PROSPERO: CRD42015015981.
PMID- 29940031
TI - Ligation of Na, K ATPase beta3 subunit on monocytes by a specific monoclonal
antibody mediates T cell hypofunction.
AB - T cells play a crucial role in orchestrating body immune responses. T cell
hyperfunction, however, leads to inflammation and induction of autoimmune
diseases. Understanding of T cell regulation mechanisms and successful modulation
of T cell responses is beneficial in treatment of disease associated to T cell
hyperresponsiveness. Our previous study indicated that monoclonal antibody (mAb)
P-3E10, a mAb to Na, K ATPase beta3 subunit, inhibited anti-CD3-induced PBMC
proliferation. In the current study, we further investigated the mechanism of mAb
P-3E10 in the induction of T cell hypofunction. We demonstrated that mAb P-3E10
decreased T cell proliferation and Th1, Th2 and Th17 cytokine production.
Monocytes were the cells playing a key role in mediation of mAb P-3E10 induced T
cell hypofunction. The inhibition of T cell activation by mAb P-3E10 required
cell contact between monocytes and T cells. The mAb P-3E10 induced the down
expression level of MHC class II and CD86 and increased IL-6, IL-10 and TNF-alpha
production of monocytes. We concluded that ligation of the Na, K ATPase beta3
subunit on monocytes by mAb P-3E10 arbitrated T cell hypofunction. This mAb might
be a promising novel immunotherapeutic antibody for the treatment of
hyperresponsive T cell associated diseases.
PMID- 29940032
TI - Evaluation of the impact of dental prophylaxis on the oral microbiota of dogs.
AB - Periodontal disease is one of the most commonly diagnosed oral diseases in dogs
and can result from undisturbed dental plaque. Dental prophylaxis is a routinely
practiced veterinary procedure, but its effects on both the plaque and oral
microbiota is not fully understood. The objectives of this study were to evaluate
the impact of dental prophylaxis on the composition of the supragingival plaque
and composite oral microbiota in clinically healthy dogs and to determine if
composite sampling could be used in lieu of sampling the plaque microbiota
directly. Thirty dogs received a dental prophylaxis. Supragingival plaque and
composite oral samples were collected just prior to, and one week after dental
prophylaxis. A subsample of 10 dogs was followed, and additional samples were
collected two and five weeks post-prophylaxis. The V4 region of the 16S rRNA gene
was used for Illumina MiSeq next-generation sequencing. Results demonstrate that
decreases in Treponema as well as increases in Moraxella and Neisseria
distinguished the plaque pre- and one week post-prophylaxis timepoints (all
P<0.05). Within the oral microbiota, the initially dominant Psychrobacter (20%
relative abundance) disappeared one week later (P<0.0001), and Pseudomonas became
the dominant taxon one week after treatment (80% relative abundance, P<0.0001). A
rapid transition back towards the pre-dental prophylaxis microbiota by five weeks
post-treatment was seen for both niches, suggesting the canine oral microbiota is
resilient. Direct comparison of the two environments yielded striking
differences, with complete separation of groups. Firmicutes (40%) and
Spirochaetes (22%) predominated in the plaque while Proteobacteria (58%) was
predominant in the oral microbiota. Greater richness was also seen in the plaque
microbiota. This study reveals that prophylaxis had a profound impact on both the
plaque and oral microbiota, and the longitudinal results help elucidate the
pathophysiology of periodontal disease. The results suggest that oral swabs are a
poor proxy for plaque samples and highlight the need to study specific oral
niches.
PMID- 29940033
TI - Binge alcohol and substance use across birth cohorts and the global financial
crisis in the United States.
AB - BACKGROUND: The social and economic consequences of the global financial crisis
(GFC) of 2007-9 has had serious impacts on population health, economic prospects,
and overall wellbeing in all generations, particularly Millennials, Generation X,
and Baby Boomers. The ways in which intergenerational inequality and global
economic crises have affected population health, particularly with respect to
excessive drinking and substance use in disadvantaged population groups has been
understudied. Consequently, in this article, we seek to characterise the effects
of the GFC on national trends in binge alcohol and substance use among
Millennials, Generation X, and Baby Boomers. By doing so, we aim to contribute to
a fuller understanding of the ways in which socioeconomic disadvantage engendered
by the GFC has disparately affected the wellbeing of these generational cohorts.
METHODS AND FINDINGS: We present results from National Survey on Drug Use and
Health from 2007-16 to characterise binge alcohol and substance use among
different generational cohorts in the United States during and after the GFC.
Bivariate descriptive analysis and maximum-likelihood logit regressions focused
on: (a) individual substances and binge drinking, (b) poly-use and (c) any use to
simultaneously model how socioeconomic, demographic, and health characteristics
were related to past-month substance use and to report the social, economic, and
demographic correlates of substance use. Socioeconomic vulnerability was captured
on a five-point scale comprised of: (1) health insurance status, (2) government
assistance, (3) income, (4) self rated health, and (5) employment status.
Millennials showed generally higher risk of binge alcohol and substance use
during 2007-16 than Generation X, while Baby Boomers generally exhibited lower
risk. Comparison of individual and poly-use patterns for the birth cohorts before
and after reveals: Millennials were at significantly increased risk of use of
binge alcohol (AOR = 1.51; 95% CI = 1.46-1.56), cocaine (AOR = 1.19; 95% CI =
1.03-1.37), heroin (AOR = 1.39; 95% CI = 1.01-1.91), and oxycontin (AOR = 2.33;
95% CI = 1.74-3.12) than Gen X while Baby Boomers were at significantly reduced
risk of all substances. Nevertheless, Millennials were at significantly reduced
risk of crack use (AOR = 0.33; 95% CI = 0.25-0.43) and poly-use (AOR = 0.56; 95%
CI = 0.45-0.70) compared to Gen X. These differences may be related to measures
of austerity and socioeconomic vulnerability. Millennials exhibited the highest
vulnerability related to austerity with an average vulnerability score of 0.97
(95% CI = 0.96-0.98) while Baby Boomers exhibited the lowest average
vulnerability score of 0.65 (95% CI = 0.64-0.66) with Generation X in between
with 0.72 (95% CI = 0.71-0.73). Increased social and economic vulnerability after
the 2007 crisis is strongly associated with higher rates of substance use in all
generations. CONCLUSION: Millennials have been especially affected by
socioeconomic changes associated with the GFC as reflected by their heightened
vulnerability and increased use of binge alcohol and other substances compared to
preceding generations. These findings suggest that attention is needed to address
disparities in socioeconomic vulnerability, relationships to substance use and
overall mental health of Millennials to mitigate the potential long term negative
impacts of the GFC. In the context of a continuing international opioid and
heroin crisis, the ways in which Millennials have been differentially affected
warrants much greater attention both from policymakers and from researchers.
PMID- 29940035
TI - Correction: Chronic use of psychotropic medications in breastfeeding women: Is it
safe?
AB - [This corrects the article DOI: 10.1371/journal.pone.0197196.].
PMID- 29940034
TI - Non-linear hierarchy of the quorum sensing signalling pathway in bloodstream form
African trypanosomes.
AB - Trypanosoma brucei, the agents of African trypanosomiasis, undergo density
dependent differentiation in the mammalian bloodstream to prepare for
transmission by tsetse flies. This involves the generation of cell-cycle
arrested, quiescent, stumpy forms from proliferative slender forms. The
signalling pathway responsible for the quorum sensing response has been
catalogued using a genome-wide selective screen, providing a compendium of
signalling protein kinases phosphatases, RNA binding proteins and hypothetical
proteins. However, the ordering of these components is unknown. To piece together
these components to provide a description of how stumpy formation arises we have
used an extragenic suppression approach. This exploited a combinatorial gene
knockout and overexpression strategy to assess whether the loss of developmental
competence in null mutants of pathway components could be compensated by ectopic
expression of other components. We have created null mutants for three genes in
the stumpy induction factor signalling pathway (RBP7, YAK, MEKK1) and evaluated
complementation by expression of RBP7, NEK17, PP1-6, or inducible gene silencing
of the proposed differentiation inhibitor TbTOR4. This indicated that the
signalling pathway is non-linear. Phosphoproteomic analysis focused on one
pathway component, a putative MEKK, identified molecules with altered expression
and phosphorylation profiles in MEKK1 null mutants, including another component
in the pathway, NEK17. Our data provide a first molecular dissection of multiple
components in a signal transduction cascade in trypanosomes.
PMID- 29940036
TI - The culprit insect but not severity of allergic reactions to bee and wasp venom
can be determined by molecular diagnosis.
AB - BACKGROUND: Allergy to bee and wasp venom can lead to life-threatening systemic
reactions. The identification of the culprit species is important for allergen
specific immunotherapy. OBJECTIVES: To determine a panel of recombinant bee and
wasp allergens which is suitable for the identification of bee or wasp as culprit
allergen sources and to search for molecular surrogates of clinical severity of
sting reactions. METHODS: Sera from eighty-seven patients with a detailed
documentation of their severity of sting reaction (Mueller grade) and who had
been subjected to titrated skin testing with bee and wasp venom were analyzed for
bee and wasp-specific IgE levels by ImmunoCAPTM. IgE-reactivity testing was
performed using a comprehensive panel of recombinant bee and wasp venom allergens
(rApi m 1, 2, 3, 4, 5 and 10; rVes v 1 and 5) by ISAC chip technology, ImmunoCAP
and ELISA. IgG4 antibodies to rApi m 1 and rVes v 5 were determined by ELISA and
IgE/IgG4 ratios were calculated. Results from skin testing, IgE serology and
IgE/IgG4 ratios were compared with severity of sting reactions. RESULTS: The
panel of rApi m 1, rApi m 10, rVes v 1 and rVes v 5 allowed identification of the
culprit venom in all but two of the 87 patients with good agreement to skin
testing. Severities of sting reactions were not associated with results obtained
by skin testing, venom-specific IgE levels or molecular diagnosis. Severe sting
reactions were observed in patients showing < 1 ISU and < 2kUA/L of IgE to Api m
1 and/or Ves v 5. CONCLUSION: We identified a minimal panel of recombinant bee
and wasp allergens for molecular diagnosis which may permit identification of bee
and/or wasp as culprit insect in venom-sensitized subjects. The severity of sting
reactions was not associated with parameters obtained by molecular diagnosis.
PMID- 29940037
TI - Correction: Prenatal and Postnatal Exposure to DDT by Breast Milk Analysis in
Canary Islands.
AB - [This corrects the article DOI: 10.1371/journal.pone.0083831.].
PMID- 29940039
TI - Correction: Randomized prospective study evaluating tenofovir disoproxil fumarate
prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients
with rituximab-based regimens to treat hematologic malignancies: The Preblin
study.
AB - [This corrects the article DOI: 10.1371/journal.pone.0184550.].
PMID- 29940038
TI - Interactions between the circadian clock and TGF-beta signaling pathway in
zebrafish.
AB - BACKGROUND: TGF-beta signaling is a cellular pathway that functions in most cells
and has been shown to play a role in multiple processes, such as the immune
response, cell differentiation and proliferation. Recent evidence suggests a
possible interaction between TGF-beta signaling and the molecular circadian
oscillator. The current study aims to characterize this interaction in the
zebrafish at the molecular and behavioral levels, taking advantage of the early
development of a functional circadian clock and the availability of light
entrainable clock-containing cell lines. RESULTS: Smad3a, a TGF-beta signaling
related gene, exhibited a circadian expression pattern throughout the brain of
zebrafish larvae. Both pharmacological inhibition and indirect activation of TGF
beta signaling in zebrafish Pac-2 cells caused a concentration dependent
disruption of rhythmic promoter activity of the core clock gene Per1b. Inhibition
of TGF-beta signaling in intact zebrafish larvae caused a phase delay in the
rhythmic expression of Per1b mRNA. TGF-beta inhibition also reversibly disrupted,
phase delayed and increased the period of circadian rhythms of locomotor activity
in zebrafish larvae. CONCLUSIONS: The current research provides evidence for an
interaction between the TGF-beta signaling pathway and the circadian clock system
at the molecular and behavioral levels, and points to the importance of TGF-beta
signaling for normal circadian clock function. Future examination of this
interaction should contribute to a better understanding of its underlying
mechanisms and its influence on a variety of cellular processes including the
cell cycle, with possible implications for cancer development and progression.
PMID- 29940040
TI - Correction: Cognitive Improvement during Treatment for Mild Alzheimer's Disease
with a Chinese Herbal Formula: A Randomized Controlled Trial.
AB - [This corrects the article DOI: 10.1371/journal.pone.0130353.].
PMID- 29940041
TI - Seedling emergence response of rare arable plants to soil tillage varies by
species.
AB - Very little information is available on emergence of rare arable plants (RAP) in
relation to soil disturbance and seed burial conditions in Europe. This
information is essential to design conservation and soil management strategies to
prevent the decline of these species in agroecosystems. The objective of this
research was to investigate the effect of soil cultivation with burial time on
the emergence and seed persistence of RAP. Seeds of 30 RAP species were collected
from Spanish arable fields and subjected to two tillage treatments: (a) no soil
disturbance, and (b) autumnal soil disturbance down to 10 cm depth every year.
The treatments simulated no-till and tilled (disking), respectively. In plots
under no-till, RAP seeds were sown at 1-cm depth. In the tilled plots, seeds were
sown homogeneously mixed in the top 1-10 cm of soil. The trial was established
every two consecutive seasons, and each trial was maintained for two years.
Annual cumulative plant emergence was calculated each year; whereas the first
trial was monitored for a third year to estimate seed longevity using a
persistence index. The response in emergence of the 30 RAP to annual tillage
varied among species. With burial time (number of years), higher emergence was
observed for seeds sown in tilled soil. This was true across all species, and
with strong season effects. The persistence index was correlated with seed
weight, species with bigger seeds had low persistence indices while no pattern
was observed for small seeded species. Most RAP species, particularly those with
high persistence, showed induction of secondary dormancy processes, highlighting
the importance of tillage to promote RAP emergence, and hence, seed bank
replenishment. Therefore, as time passes the absence of soil tillage may
represent a driver of RAP seed bank decline for those species with secondary
dormancy processes. In conclusion, it is important to design soil management
strategies, such as regular tillage to promote emergence, on a species basis to
preserve RAP in Europe.
PMID- 29940042
TI - Low prevalence of HTLV1/2 infection in a population of immigrants living in
southern Italy.
AB - AIMS: To assess the prevalence of HTLV-1 and HTLV-2 infections in a cohort of
immigrants living in southern Italy. FINDINGS: We screened for antibody to HTLV
1/2 infection 1,498 consecutive immigrants born in endemic areas (sub-Saharan
Africa or southern-Asia) by a commercial chemiluminescent microparticle
immunoassay. If confirmed in a Western blot assay, which differentiates anti-HTLV
1 from anti-HTLV-2, the positive sera were tested for specific HTLV RNA by a home
made PCR. The immigrants investigated were more frequently males (89.05%), young
(median age 26 years), with a low level of education (median schooling 6 years),
born in sub-Saharan Africa (79.70%). They had been living in Italy for a median
period of 5 months. Only one (0.07%) subject was anti-HTLV-1 -positive/HTLV-1 RNA
negative; he was an asymptomatic 27-year-old male from Nigeria with 6 years'
schooling who stated unsafe sexual habits and unsafe injection therapy.
CONCLUSIONS: The data suggest screening for HTLV1 and HTLV-2 infections all blood
donors to Italy from endemic countries at least on their first donation; however,
a cost-effectiveness study is needed to clarify this topic.
PMID- 29940043
TI - Effect of task difficulty on blood-oxygen-level-dependent signal: A functional
magnetic resonance imaging study in a motion discrimination task.
AB - There is much evidence that neural activity in the human brain is modulated by
task difficulty, particularly in visual, frontal, and parietal cortices. However,
some basic psychophysical tasks in visual perception do not give rise to this
expected effect, at least not in the visual cortex. In the current study, we used
functional magnetic resonance imaging (fMRI) to record brain activity while
systematically manipulating task difficulty in a motion discrimination task, by
varying the angular difference between the motion direction of random dots and a
reference direction. We used both a blocked and an event-related design, and
presented stimuli in both central and peripheral vision. The behavioral
psychometric function, across angular differences of 3 degrees , 9 degrees , 15
degrees , or 80 degrees , spanned the full response range, as expected. The mean
blood oxygen level dependent (BOLD) signals were also correlated within
participants between the blocked and event-related designs, across all brain
areas tested. Within the visual cortex, the voxel response patterns correlated
more within-conditions (e.g., 3 degrees and 3 degrees ) than between-conditions
(e.g., 3 degrees and 9 degrees ), in both designs, further attesting to the
reasonable quality of the BOLD data. Nevertheless, the BOLD-o-metric functions
(i.e., BOLD activity as a function of task difficulty) were flat in the whole
brain and region-of-interest (ROI) analyses, including in the visual cortex, the
parietal cortex, in both designs, and in foveal and peripheral visual fields
alike. Indeed, there was little difference between BOLD activity during the 3
degrees and 80 degrees conditions. Some suggestive evidence of difficulty
modulation was revealed only in the superior and inferior frontal gyri for the
blocked design. We conclude that, in motion discrimination, there is no
systematic BOLD modulation that accompanies the standard psychometric function
across different hierarchies of cortical areas, except for the frontal lobe of
the brain.
PMID- 29940044
TI - Correction: Factors affecting forest area change in Southeast Asia during 1980
2010.
AB - [This corrects the article DOI: 10.1371/journal.pone.0197391.].
PMID- 29940045
TI - Correction: Genetic diversity, genetic structure and diet of ancient and
contemporary red deer (Cervus elaphus L.) from north-eastern France.
AB - [This corrects the article DOI: 10.1371/journal.pone.0189278.].
PMID- 29940046
TI - Extracellular matrix surface regulates self-assembly of three-dimensional
placental trophoblast spheroids.
AB - The incorporation of the extracellular matrix (ECM) is essential for generating
in vitro models that truly represent the microarchitecture found in human
tissues. However, the cell-cell and cell-ECM interactions in vitro remains poorly
understood in placental trophoblast biology. We investigated the effects of
varying the surface properties (surface thickness and stiffness) of two ECMs,
collagen I and Matrigel, on placental trophoblast cell morphology, viability,
proliferation, and expression of markers involved in differentiation/syncytial
fusion. Most notably, thicker Matrigel surfaces were found to induce the self
assembly of trophoblast cells into 3D spheroids that exhibited thickness
dependent changes in viability, proliferation, syncytial fusion, and gene
expression profiles compared to two-dimensional cultures. Changes in F-actin
organization, cell spread morphologies, and integrin and matrix metalloproteinase
gene expression profiles, further reveal that the response to surface thickness
may be mediated in part through cellular stiffness-sensing mechanisms. Our
derivation of self-assembling trophoblast spheroid cultures through regulation of
ECM surface alone contributes to a deeper understanding of cell-ECM interactions,
and may be important for the advancement of in vitro platforms for research or
diagnostics.
PMID- 29940048
TI - Correction: Intact memory for local and distal cues in male and female rats that
lack adult neurogenesis.
AB - [This corrects the article DOI: 10.1371/journal.pone.0197869.].
PMID- 29940047
TI - Factors associated with diversity, quantity and zoonotic potential of
ectoparasites on urban mice and voles.
AB - Wild rodents are important hosts for tick larvae but co-infestations with other
mites and insects are largely neglected. Small rodents were trapped at four study
sites in Berlin, Germany, to quantify their ectoparasite diversity. Host
specific, spatial and temporal occurrence of ectoparasites was determined to
assess their influence on direct and indirect zoonotic risk due to mice and voles
in an urban agglomeration. Rodent-associated arthropods were diverse, including
63 species observed on six host species with an overall prevalence of 99%. The
tick Ixodes ricinus was the most prevalent species, found on 56% of the rodents.
The trapping location clearly affected the presence of different rodent species
and, therefore, the occurrence of particular host-specific parasites. In Berlin,
fewer temporary and periodic parasite species as well as non-parasitic species
(fleas, chiggers and nidicolous Gamasina) were detected than reported from rural
areas. In addition, abundance of parasites with low host-specificity (ticks,
fleas and chiggers) apparently decreased with increasing landscape fragmentation
associated with a gradient of urbanisation. In contrast, stationary
ectoparasites, closely adapted to the rodent host, such as the fur mites
Myobiidae and Listrophoridae, were most abundant at the two urban sites. A direct
zoonotic risk of infection for people may only be posed by Nosopsyllus fasciatus
fleas, which were prevalent even in the city centre. More importantly,
peridomestic rodents clearly supported the life cycle of ticks in the city as
hosts for their subadult stages. In addition to trapping location, season, host
species, body condition and host sex, infestation with fleas, gamasid Laelapidae
mites and prostigmatic Myobiidae mites were associated with significantly altered
abundance of I. ricinus larvae on mice and voles. Whether this is caused by
predation, grooming behaviour or interaction with the host immune system is
unclear. The present study constitutes a basis to identify interactions and
vector function of rodent-associated arthropods and their potential impact on
zoonotic diseases.
PMID- 29940049
TI - Notice of Retraction.
AB - The article "Three-Dimensional Bone Augmentation and Immediate Implant Placement
via Transcrestal Sinus Lift: 8-Year Clinical Outcomes," by Rizzo et al, which was
published in the May/June issue (Int J Periodontics Restorative Dent 2018;38:423
429. doi 10.11607/prd.476) has been retracted by the publisher. The article was
published in error.
PMID- 29940050
TI - Hemiarthroplasty Is an Option for Patients Older Than 70 Years With Glenohumeral
Osteoarthritis.
AB - Hemiarthroplasty (HA) of the shoulder has several potential advantages over total
shoulder arthroplasty (TSA), particularly in the elderly population. This study
reviewed long-term results of HA and TSA in patients older than 70 years with
glenohumeral osteoarthritis. During a 30-year period, 403 shoulders had undergone
HA (n=74) or TSA (n=329) for glenohumeral osteoarthritis. Outcome measures
included pain, range of motion, and postoperative modified Neer ratings. All
patients were included in the mortality and revision analyses. A total of 289
shoulders (44 HAs and 245 TSAs; mean patient age, 75 years) with a minimum of 5
years of follow-up or follow-up until revision were included. Both groups showed
significant improvements in pain, abduction, and external rotation. No
significant differences were detected between groups in postoperative pain, range
of motion, or modified Neer ratings. Operative time was significantly lower in
the HA group. There was no statistically significant difference detected in
implant revision-free survival between TSA and HA (hazard ratio, 3.09) or in
overall survival hazard ratio. At long-term follow-up, both HAs and TSAs provided
good function in the elderly population. Patients who underwent TSA and patients
who underwent HA had similar results, but the latter had a shorter operative time
and lower revision rate. Hemiarthroplasty is a reasonable option for patients
older than 70 years with end-stage glenohumeral osteoarthritis. [Orthopedics.
2018; 41(4):222-228.].
PMID- 29940051
TI - Surgical Treatment of Recurrent Lumbar Disk Herniation: A Systematic Review and
Meta-analysis.
AB - Consensus is lacking regarding optimal surgical treatment of recurrent lumbar
disk herniation. A systematic search of multiple databases was conducted for
studies evaluating outcomes after treatment for recurrent lumbar disk herniation.
Treatment options included decompression surgeries and fusion surgeries. Although
fusion surgeries eliminated re-recurrence of disk herniation, this coincided with
higher incidences of complications and reoperation. Decompression surgeries and
fusion surgeries both resulted in improvements in Japanese Orthopaedic
Association, Oswestry Disability Index, and visual analog scale back and leg
scores postoperatively (P<.05). The complication risk profiles of decompression
surgeries and fusion surgeries must be balanced with the risk of disk herniation
re-recurrence, as both procedures lead to improvements in functional outcomes.
[Orthopedics. 2018; 41(4):e457-e469.].
PMID- 29940052
TI - Direct Visualization of Suspensory Fixation Deployment in Knee Ligament
Reconstructions Without Fluoroscopic Imaging.
AB - The authors describe a technique for visualizing the deployment of femoral
suspensory fixation during ligament reconstructions that avoids the need for
intraoperative fluoroscopic radiographs. Many surgeons currently use
intraoperative fluoroscopic radiographs to confirm satisfactory deployment of the
suspensory button on the femur; however, this technique involves prolonged
surgical time, additional costs, and radiation exposure to the surgical team and
patient. The authors' technique uses novel leg and camera positioning to allow
for direct visualization of the button deployment. This technique can greatly
improve operating room efficiency, save money, and decrease radiation exposure
during surgery. [Orthopedics. 2018; 41(4):e587-e590.].
PMID- 29940053
TI - Medical Malpractice in Orthopedic Surgery: A Westlaw-Based Demographic Analysis.
AB - A recent study that evaluated the risk of facing a malpractice claim by physician
specialty found that orthopedic surgeons were at a significantly greater risk of
being sued than other medical specialists. To date, no studies have characterized
trends in orthopedic surgery malpractice claims. The Westlaw legal database was
used to locate state and federal jury verdicts and settlements related to medical
malpractice and orthopedic surgery from 2010 to 2016. Eighty-one cases were
analyzed. The mean age of the affected patients and/or plaintiffs was 53.4 years.
Spine surgery (21 cases; 25.9%), knee surgery (17 cases; 21.0%), and hip surgery
(11 cases; 13.6%) were litigated most often. Procedural error (71 cases; 87.7%)
and negligence (58 cases; 71.6%) were the 2 most commonly cited reasons for
litigation. The jury found in favor of the defendant in most (50 cases; 61.7%) of
the cases. The mean plaintiff (17 cases; 21.0%) verdict payout was $3,015,872,
and the mean settlement (13 cases; 16.0%) value was $1,570,833. Unnecessary
surgery (odds ratio [OR], 12.29; 95% confidence interval [CI], 1.91-108.46;
P=.040) and surgery resulting in death (OR, 26.26; 95% CI, 2.55-497.42; P=.040)
were significant predictors of a verdict in favor of the plaintiff. Patient death
(OR, 0.05; 95% CI, 0.01-0.38; P=.021) and male patient sex (OR, 0.26; 95% CI,
0.09-0.71; P=.033) were significant negative predictors of a verdict in favor of
the defendant. The jury found in favor of the defendant orthopedic surgeon in
most cases. Procedural error and/or negligence were cited most commonly by the
plaintiffs as the bases for the claims. Verdicts in favor of the plaintiffs
resulted in payouts nearly double those of settlements. [Orthopedics. 2018;
41(5):e615-e620.].
PMID- 29940054
TI - Comparison of the Clinical Outcomes of Open Surgery Versus Arthroscopic Surgery
for Chronic Refractory Lateral Epicondylitis of the Elbow.
AB - Numerous surgical options have been introduced for the treatment of chronic
refractory lateral epicondylitis of the elbow, but it remains unclear which
option is superior. The clinical outcomes of an open surgery group and an
arthroscopic surgery group were evaluated, and the results of the 2 procedures
were compared. From among patients with lateral epicondylitis refractory to 6
months of conservative treatment, 68 patients satisfying study criteria were
recruited. Open surgery was performed in 34 cases (group 1), and arthroscopic
surgery was performed in 34 cases (group 2). Compared with preoperatively, the 2
groups had significantly improved values for grip strength, range of motion, and
Disabilities of the Arm, Shoulder and Hand score at 12 months postoperatively.
Group 1 had significantly greater improvements in grip strength and visual analog
scale pain score compared with group 2 (P=.048 vs P=.006). Group 2 had
significantly greater (P=.045) improvement in pronation compared with group 1.
Group 2 returned to work sooner than group 1. On the questionnaire regarding
satisfaction with surgery 24 months postoperatively, 4 patients (12%) in group 2
reported dissatisfaction compared with no patients in group 1. Open surgery and
arthroscopic surgery both yielded good clinical results. Nonetheless, for
patients requiring muscle strength or having severe pain at work, open surgery
would be more effective. [Orthopedics. 2018; 41(4):237-247.].
PMID- 29940055
TI - The Prolonged Analgesic Efficacy of an Ultrasound-Guided Single-Shot Adductor
Canal Block in Patients Undergoing Total Knee Arthroplasty.
AB - In this prospective, randomized, placebo-controlled study, the authors compared
the analgesic efficacy of the single-shot adductor canal block (SS-ACB) vs the
continuous adductor canal block (C-ACB) with intermittent boluses during the 72
hour postoperative period. Seventy-five patients randomly received the following:
a single shot of 20 mL of 0.5% ropivacaine preoperatively followed by
intermittent saline boluses at 12 hours and 24 hours postoperatively (SS-ACB
group); 20 mL of 0.5% ropivacaine preoperatively and 12 hours and 24 hours
postoperatively (C-ACB group); or saline preoperatively and postoperatively
(control group). The primary outcome was visual analog scale pain scores with
movement on postoperative day 1. The dynamic pain scores of the 2 ACB groups were
equivalent and were lower than those of the control group on postoperative day 1.
Compared with the control group, the 2 ACB groups were less likely to use opioids
on the operative day and the first 2 postoperative days. The patients in the
control group and the C-ACB group exhibited less quadriceps muscle strength than
those in the SS-ACB group on postoperative day 1. The time required for an SS-ACB
was markedly shorter than that required for an indwelling adductor canal
catheter. Further, each adductor canal catheter cost $80. Patients who received a
single block reported more satisfaction with their pain-relief treatment. Given
the similar analgesic effect but better quadriceps muscle strength, easier
execution, and higher patient satisfaction, the SS-ACB may be more suitable for
total knee arthroplasty patients than the C-ACB. [Orthopedics. 2018; 41(5):e607
e614.].
PMID- 29940056
TI - Debra Patt on How the Management of Cancer is Changing as Patients Live Longer.
PMID- 29940057
TI - Newly Diagnosed Lung Cancer: Which Molecular Tests Are Needed for Optimal
Treatment Decision Making?
AB - The management of advanced non-small-cell lung cancer (NSCLC) has changed
dramatically over the past few years due to our expanded knowledge of the
molecular basis of lung cancer (driver mutations and immune targets) and drugs
that affect these pathways, namely targeted agents and checkpoint inhibitors.
Consequently, it is important to test patients with newly diagnosed advanced
NSCLC for potentially significant molecular abnormalities prior to the initiation
of treatment. This requires close coordination between the surgical pathologist,
the molecular pathologist, and the medical oncologist to ensure that the biopsy
specimen is used judiciously to get all necessary information. In this article, I
suggest an approach to the diagnostic evaluation of patients with newly diagnosed
advanced NSCLC, in an attempt to identify the best treatment options for each.
PMID- 29940058
TI - How LGL T-Cell Leukemia at 19 Gave Me Empathy for My Patients-and My Colleagues.
PMID- 29940059
TI - Point: Does Chemoimmunotherapy Still Have a Role in CLL? Chemoimmunotherapy With
FCR Is Still an Important Option in CLL.
PMID- 29940060
TI - Counterpoint: Does Chemoimmunotherapy Still Have a Role in CLL? Chemotherapy Can
Be Eliminated in the Management of CLL.
PMID- 29940061
TI - A 35-Year-Old Woman With a Change in HER2 Expression Following Neoadjuvant
Chemotherapy for Invasive Breast Cancer.
PMID- 29940062
TI - How to Decide Which DLBCL Patients Should Receive CNS Prophylaxis.
AB - Secondary central nervous system (CNS) relapse in aggressive non-Hodgkin lymphoma
(NHL) is a dismal diagnosis with poor outcomes. While prophylaxis against
secondary CNS disease is recommended in patients with highly aggressive NHLs,
such as Burkitt lymphoma, patients with diffuse large B-cell lymphoma (DLBCL)
present a challenging clinical dilemma due to an inherently lower risk of CNS
relapse. Current guidelines suggest that prophylaxis may benefit DLBCL patients
at high risk for CNS relapse; however, it has been difficult to define which
patients are truly at high risk. Many studies have attempted to clarify the
issue, with conflicting results. Here we review current prognostic models, risk
factors, and prophylaxis methods to provide a practical approach to preventing
CNS relapse in patients with DLBCL.
PMID- 29940063
TI - Understanding the Benefits of Acupuncture Treatment for Cancer Pain Management.
AB - This article summarizes the current evidence regarding the use of acupuncture for
pain management in cancer patients. It includes a description of how acupuncture
is thought to work and what the intervention entails, data on acupuncture for
managing pain caused by cancer or by cancer treatment (radiation, chemotherapy,
endocrine therapy), how acupuncture is practiced in the US medical system,
discussion of safety issues, and practical tips on how to integrate acupuncture
into cancer care.
PMID- 29940064
TI - Immunotherapy for Prostate Cancer: Where Do We Go From Here?-PART 2: Checkpoint
Inhibitors, Immunotherapy Combinations, Tumor Microenvironment Modulation, and
Cellular Therapies.
AB - Therapeutic approaches that harness the power of the immune system to eliminate
cancer cells have produced a paradigm shift in the management of a variety of
malignancies. Prostate cancer has been a particularly active area of
investigation in cancer immunotherapy, with significant laboratory and clinical
evidence suggesting that this disease can be a viable target for cytotoxic immune
cells. In the first article of this series, we discussed the diverse vaccination
approaches that have been employed to prime native antigen-specific responses
against prostate cancer, highlighting successes such as sipuleucel-T, as well as
the significant challenges that remain. Here we focus on alternative methods of
harnessing both adaptive and innate antitumor immunity to target prostate cancer
cells. Approaches that enhance the activation of T cells, modulation of the tumor
microenvironment to abrogate its inherent immunosuppressive mechanisms, and
engineering of antigen-specific antibody and cellular products to target tumor
cells will be discussed. We will then look ahead to provide a perspective on how
this growing collection of immunotherapeutic approaches may ultimately be
combined to target prostate cancer from a variety of angles.
PMID- 29940065
TI - The Use of Surgery and Radiotherapy as Treatment of Regional Nodes in Breast
Cancer Patients.
AB - Ipsilateral regional nodal status is an important independent prognostic factor
for patients with breast cancer. Several decisions regarding local therapy are
necessary for patients found to have pathologically involved lymph node(s). This
article reviews the role of completion dissection and/or radiation therapy in
patients found to have positive sentinel lymph node(s), taking into consideration
use of mastectomy vs lumpectomy, tumor characteristics, tumor biology, plans for
systemic therapy, and patient preferences. Published literature and current
guidelines are reviewed, with emphasis on controversial topics such as regional
nodal and postmastectomy radiation therapy for patients with one to three
positive nodes. Choice of field design in patients undergoing radiation therapy
will also be highlighted. Unique clinical situations such as locoregional
treatment in patients receiving neoadjuvant chemotherapy and the emerging role of
tumor biology and molecular assays in local therapy decision making will also be
discussed.
PMID- 29940066
TI - A framework for the identification of promising bio-based chemicals.
AB - Recent progress in metabolic engineering and synthetic biology enables the use of
microorganisms for the production of chemicals-"bio-based chemicals." However, it
is still unclear which chemicals have the highest economic prospect. To this end,
we develop a framework for the identification of such promising ones.
Specifically, we first develop a genome-scale constraint-based metabolic modeling
approach, which is used to identify a candidate pool of 209 chemicals (together
with the estimated yield, productivity, and residence time for each) from the
intersection of the high-production-volume chemicals and the KEGG and MetaCyc
databases. Second, we design three screening criteria based on a chemical's
profit margin, market volume, and market size. The total process cost, including
the downstream separation cost, is systematically incorporated into the
evaluation. Third, given the three aforementioned criteria, we identify 32
products as economically promising if the maximum yields can be achieved, and 22
products if the maximum productivities can be achieved. The breakeven titer that
renders zero profit margin for each product is also presented. Comparisons
between extracellular and intracellular production, as well as Escherichia coli
and Saccharomyces cerevisiae systems are also discussed. The proposed framework
provides important guidance for future studies in the production of bio-based
chemicals. It is also flexible in that the databases, yield estimations, and
criteria can be modified to customize the screening.
PMID- 29940067
TI - Rational approach to improve ansamitocin P-3 production by integrating pathway
engineering and substrate feeding in Actinosynnema pretiosum.
AB - Ansamitocin P-3 (AP-3) produced by Actinosynnema pretiosum is an important
antitumor agent for cancer treatment, but its market supply suffers from a low
production titer. The role of AP-3 unusual glycolate unit supply on its
biosynthesis was investigated in this work by overexpressing the responsible gene
cluster asm13-17 in A. pretiosum (WT). As a result, the accumulation of AP-3 and
its intermediate glyceryl-S-ACP in the asm13-17-overexpressed strain (Oasm13-17)
versus WT was enhanced by 1.94 and 1.49-fold, respectively. To provide a higher
supply of another precursor 3-amino-5-hydroxybenzoic acid, asmUdpg was also
overexpressed in Oasm13-17 (Oasm13-17:asmUdpg), and an improved AP-3 titer of
680.5 mg/L was achieved in shake flasks. To further enhance the AP-3 titer, a
rational fed-batch strategy was developed in bioreactor fermentation of Oasm13
17:asmUdpg; and by pulse feeding 15 g/L fructose and 1.64 g/L isobutanol at 60,
96, and 120 hr, the AP-3 production level reached 757.7 mg/L, which is much
higher than ever reported in bioreactors. This work demonstrated that a rational
approach combining precursor pathway engineering with substrate feeding was very
effective in enhancing the AP-3 titer, and this enabling methodology would be
helpful to industrial production of this eye-catching drug.
PMID- 29940069
TI - Enhanced production of poly-gamma-glutamic acid by improving ATP supply in
metabolically engineered Bacillus licheniformis.
AB - Poly-gamma-glutamic acid (gamma-PGA) is an important multifunctional biopolymer
with various applications, for which adenosine triphosphate (ATP) supply plays a
vital role in biosynthesis. In this study, the enhancement of gamma-PGA
production was attempted through various approaches of improving ATP supply in
the engineered strains of Bacillus licheniformis. The first approach is to
engineer respiration chain branches of B. licheniformis, elimination of
cytochrome bd oxidase branch reduced the maintenance coefficient, leading to a
19.27% increase of gamma-PGA yield. The second approach is to introduce
Vitreoscilla hemoglobin (VHB) into recombinant B. licheniformis, led to a 13.32%
increase of gamma-PGA yield. In the third approach, the genes purB and adK in ATP
biosynthetic pathway were respectively overexpressed, with the AdK overexpressed
strain increased gamma-PGA yield by 14.69%. Our study also confirmed that the
respiratory nitrate reductase, NarGHIJ, is responsible for the conversion of
nitrate to nitrite, and assimilatory nitrate reductase NasBC is for conversion of
nitrite to ammonia. Both NarGHIJ and NasBC were positively regulated by the two
component system ResD-ResE, and overexpression of NarG, NasC, and ResD also
improved the ATP supply and the consequent gamma-PGA yield. Based on the above
individual methods, a method of combining the deletion of cydBC gene and
overexpression of genes vgB, adK, and resD were used to enhance ATP content of
the cells to 3.53 MUmol/g of DCW, the mutant WX-BCVAR with this enhancement
produced 43.81 g/L of gamma-PGA, a 38.64% improvement compared to wild-type
strain WX-02. Collectively, our results demonstrate that improving ATP content in
B. licheniformis is an efficient strategy to improve gamma-PGA production.
PMID- 29940068
TI - Resemblance of the human liver sinusoid in a fluidic device with biomedical and
pharmaceutical applications.
AB - Maintenance of the complex phenotype of primary hepatocytes in vitro represents a
limitation for developing liver support systems and reliable tools for biomedical
research and drug screening. We herein aimed at developing a biosystem able to
preserve human and rodent hepatocytes phenotype in vitro based on the main
characteristics of the liver sinusoid: unique cellular architecture, endothelial
biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver
sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic
human or control rat livers and cultured in conventional in vitro platforms or
within our liver-resembling device. Hepatocytes phenotype, function, and response
to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo
sinusoidal environment within our biosystem, primary human and rat hepatocytes
cocultured with functional LSEC maintained morphology and showed high albumin and
urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4)
activity, and maintained expression of hepatocyte nuclear factor 4 alpha
(hnf4alpha) and transporters, showing delayed hepatocyte dedifferentiation. In
addition, differentiated hepatocytes cultured within this liver-resembling device
responded to acute treatment with known hepatotoxic drugs significantly different
from those seen in conventional culture platforms. In conclusion, this study
describes a new bioengineered device that mimics the human sinusoid in vitro,
representing a novel method to study liver diseases and toxicology.
PMID- 29940070
TI - Emotional Distress, Bullying Victimization, and Protective Factors Among
Transgender and Gender Diverse Adolescents in City, Suburban, Town, and Rural
Locations.
AB - PURPOSE: Understanding the root causes of the substantial disparities in risk and
protective factors among transgender and gender diverse (TGD) adolescents is
essential to the development and expansion of resources and supports for this
vulnerable population. This study examines differences in emotional distress,
bullying victimization, and protective factors among TGD high school students in
city, suburban, town, and rural locations. METHODS: Data come from a statewide
school-based survey conducted in Minnesota in 2016 (n = 2,168 TGD youth).
Analysis of covariance models were used to predict the prevalence of multiple
indicators of emotional distress, bullying victimization, and protective factors
across the 4 location categories, with multiple adjustments. FINDINGS:
Significant linear trends were observed for 2 emotional distress outcomes and 2
bullying victimization outcomes, with urban TGD students having the lowest rates
and rural having the highest prevalences. Additional significant differences in
emotional distress were noted, with unexpectedly high rates of depressive
symptoms and suicidal ideation among suburban students. CONCLUSIONS: Helping TGD
adolescents in all types of locations identify resources and supportive
professionals is critical to supporting this population.
PMID- 29940071
TI - Rapid thermal adaptation in a marine diatom reveals constraints and trade-offs.
AB - Rapid evolution in response to environmental change will likely be a driving
force determining the distribution of species across the biosphere in coming
decades. This is especially true of microorganisms, many of which may evolve in
step with warming, including phytoplankton, the diverse photosynthetic microbes
forming the foundation of most aquatic food webs. Here we tested the capacity of
a globally important, model marine diatom Thalassiosira pseudonana, for rapid
evolution in response to temperature. Selection at 16 and 31 degrees C for 350
generations led to significant divergence in several temperature response traits,
demonstrating local adaptation and the existence of trade-offs associated with
adaptation to different temperatures. In contrast, competitive ability for
nitrogen (commonly limiting in marine systems), measured after 450 generations of
temperature selection, did not diverge in a systematic way between temperatures.
This study shows how rapid thermal adaptation affects key temperature and
nutrient traits and, thus, a population's long-term physiological, ecological,
and biogeographic response to climate change.
PMID- 29940073
TI - Early planned removal versus expectant management of peripherally inserted
central catheters to prevent infection in newborn infants.
AB - BACKGROUND: Duration of use may be a modifiable risk factor for central venous
catheter-associated bloodstream infection in newborn infants. Early planned
removal of peripherally inserted central catheters (PICCs) is recommended as a
strategy to reduce the incidence of infection and its associated morbidity and
mortality. OBJECTIVES: To determine the effectiveness of early planned removal of
PICCs (up to two weeks after insertion) compared to an expectant approach or a
longer fixed duration in preventing bloodstream infection and other complications
in newborn infants. SEARCH METHODS: We searched of the Cochrane Central Register
of Controlled Trials (CENTRAL; 2018, Issue 4), Ovid MEDLINE, Embase, Maternity &
Infant Care Database, and the Cumulative Index to Nursing and Allied Health
Literature (CINAHL) (until April 2018), and conference proceedings and previous
reviews. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials
that assessed the effect of early planned removal of umbilical venous catheters
(up to two weeks after insertion) compared to an expectant management approach or
a longer fixed duration in preventing bloodstream infection and other
complications in newborn infants. DATA COLLECTION AND ANALYSIS: Two review
authors assessed trial eligibility independently. We planned to analyse any
treatment effects in the individual trials and report the risk ratio and risk
difference for dichotomous data and mean difference for continuous data, with
respective 95% confidence intervals. We planned to use a fixed-effect model in
meta-analyses and explore potential causes of heterogeneity in sensitivity
analyses. We planned to assess the quality of evidence for the main comparison at
the outcome level using "Grading of Recommendations Assessment, Development and
Evaluation" (GRADE) methods. MAIN RESULTS: We did not identify any eligible
randomised controlled trials. AUTHORS' CONCLUSIONS: There are no trial data to
guide practice regarding early planned removal versus expectant management of
PICCs in newborn infants. A simple and pragmatic randomised controlled trial is
needed to resolve the uncertainty about optimal management in this common and
important clinical dilemma.
PMID- 29940074
TI - MtMOT1.2 is responsible for molybdate supply to Medicago truncatula nodules.
AB - Symbiotic nitrogen fixation in legume root nodules requires a steady supply of
molybdenum for synthesis of the iron-molybdenum cofactor of nitrogenase. This
nutrient has to be provided by the host plant from the soil, crossing several
symplastically disconnected compartments through molybdate transporters,
including members of the MOT1 family. Medicago truncatula Molybdate Transporter
(MtMOT) 1.2 is a Medicago truncatula MOT1 family member located in the endodermal
cells in roots and nodules. Immunolocalization of a tagged MtMOT1.2 indicates
that it is associated to the plasma membrane and to intracellular membrane
systems, where it would be transporting molybdate towards the cytosol, as
indicated in yeast transport assays. Loss-of-function mot1.2-1 mutant showed
reduced growth compared with wild-type plants when nitrogen fixation was required
but not when nitrogen was provided as nitrate. While no effect on molybdenum
dependent nitrate reductase activity was observed, nitrogenase activity was
severely affected, explaining the observed difference of growth depending on
nitrogen source. This phenotype was the result of molybdate not reaching the
nitrogen-fixing nodules, since genetic complementation with a wild-type MtMOT1.2
gene or molybdate-fortification of the nutrient solution, both restored wild-type
levels of growth and nitrogenase activity. These results support a model in which
MtMOT1.2 would mediate molybdate delivery by the vasculature into the nodules.
PMID- 29940075
TI - Nutrition Management of Necrotizing Enterocolitis.
AB - Necrotizing enterocolitis (NEC) is one of the most significant causes of
morbidity and mortality among premature infants. The exact cause is considered
multifactorial and related to gastrointestinal immaturity, inflammation and
enteral feeding. The role of nutrition is vitally important in NEC. The main
modifiable risk factor is the introduction and advancement of enteral feedings.
After an infant has recovered from NEC, enteral feeds should be cautiously
resumed to prevent injury from prolonged use of parenteral nutrition. The
logistics of how, when, and what to feed are somewhat unclear and often depend on
the severity of the disease. For patients with an enterostomy, refeeding the
distal intestine with the small-intestinal ostomy output may improve bowel growth
and prevent long-term complications.
PMID- 29940072
TI - Vascularized microfluidic platforms to mimic the tumor microenvironment.
AB - Microfluidic technology has led to the development of advanced in vitro tumor
platforms that overcome the challenges of in vivo animal and in vitro two
dimensional models. This paper presents platform designs and methods used to
develop complex vascularized in vitro models to mimic the tumor microenvironment.
Features of these platforms include a continuous, aligned endothelium that allows
for cell-cell interactions between vasculature and tumor cells. A novel platform
for fabrication of a single endothelialized microchannel encased within a
collagen platform hosting breast cancer cells was developed and utilized to study
the influence of cellular interaction on transport phenomenon through vasculature
in a hyperpermeable tumor microenvironment. This platform relies on subtractive
tissue engineering fabrication techniques. Through confocal imaging we have
demonstrated that the platform produces enhanced vessel leakiness recapitulating
physiological features of the tumor microenvironment. The influence of tumor
endothelial interactions on transport of particles was also demonstrated.
Additionally, we designed two more complex and intricate endothelialized
microfluidic networks by combining lithographic techniques with additive tissue
engineering methods. We created a network platform consisting of interconnected
microchannels to model a highly vascularized system and successfully perfused the
system with fluorescent particles. Finally, we developed a physiologically
representative in vitro microfluidic platform with vasculature patterned from in
vivo data showing the versatility of these systems to replicate the complex
geometries of tumor microvasculature and dynamically measured particle transport.
Overall, we have shown the ability to develop functional microfluidic vascular
tumor platforms of varying complexities and demonstrated their utility for
studying spatial particle transport within these systems.
PMID- 29940076
TI - A quantitative, risk-based approach to the management of neonatal early-onset
sepsis.
PMID- 29940077
TI - Untangling the mechanism of 3-methyladenine in enhancing the specific
productivity: Transcriptome analysis of recombinant Chinese hamster ovary cells
treated with 3-methyladenine.
AB - 3-Methyladenine (3-MA) is a chemical additive that enhances the specific
productivity (q p ) in recombinant Chinese hamster ovary (rCHO) cell lines.
Different from its widely known function of inhibiting autophagy, 3-MA has
instead shown to increase autophagic flux in various rCHO cell lines. Thus, the
mechanism by which 3-MA enhances the qp requires investigation. To evaluate the
effect of 3-MA on transcriptome dynamics in rCHO cells, RNA-seq was performed
with Fc-fusion protein-producing rCHO cells treated with 3-MA. By analyzing genes
that were differentially expressed following the addition of 3-MA during culture,
the role of 3-MA in the biological processes of rCHO cells was identified. One
pathway markedly influenced by the addition of 3-MA was the unfolded protein
response (UPR). Having a close relationship with autophagy, the UPR reestablishes
protein-folding homeostasis under endoplasmic reticulum (ER) stress. The addition
of 3-MA increased the expression of key regulators of the UPR, such as Atf4,
Ddit3, and Creb3l3, further supporting the idea that the enhancement of ER
capacity acts as a key in increasing the qp . Consequently, the downstream
effectors of UPR, which include autophagy-promoting genes, were upregulated as
well. Hence, the role of 3-MA in increasing UPR pathway could have made a salient
contribution to the increased autophagic flux in rCHO cells. Taken together,
transcriptome analysis improved the understanding of the role of 3-MA in gene
expression dynamics in rCHO cells and its mechanism in enhancing the qp .
PMID- 29940078
TI - Descemet's membrane endothelial keratoplasty (DMEK) versus Descemet's stripping
automated endothelial keratoplasty (DSAEK) for corneal endothelial failure.
AB - BACKGROUND: Corneal endothelial transplantation has become the gold standard for
the treatment of corneal endothelial dysfunctions, replacing full thickness
transplantation, known as penetrating keratoplasty. Corneal endothelial
transplantation has been described using two different techniques: Descemet's
membrane endothelial keratoplasty (DMEK) and Descemet's stripping automated
endothelial keratoplasty (DSAEK). Both are still performed worldwide. OBJECTIVES:
To compare the effectiveness and safety of Descemet's membrane endothelial
keratoplasty (DMEK) versus Descemet's stripping automated endothelial
keratoplasty (DSAEK) for the treatment of corneal endothelial failure in people
with Fuch's endothelial dystropy (FED) and pseudophakic bullous keratopathy
(PBK). SEARCH METHODS: We searched the Cochrane Central Register of Controlled
Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register)
(2017, Issue 7); MEDLINE Ovid; Embase Ovid; LILACS BIREME; the ISRCTN registry;
ClinicalTrials.gov and the World Health Organization (WHO) International Clinical
Trials Registry Platform (ICTRP). The date of the search was 11 August 2017.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non
randomised paired, contralateral-eye studies in any setting where DMEK was
compared with DSAEK to treat people with corneal endothelial failure. DATA
COLLECTION AND ANALYSIS: Two review authors independently screened the search
results, assessed trial quality and extracted data using the standard
methodological procedures expected by Cochrane. Our primary outcome was best
corrected visual acuity (BCVA) measured in logarithm of the Minimum Angle of
Resolution (logMAR). Secondary outcomes were endothelial cell count, graft
rejection, primary graft failure and graft dislocation. We graded the risk of
bias of non-randomised studies (NRSs) using ROBINS-I. MAIN RESULTS: We did not
identify any RCTs but found four non-randomised studies (NRSs) including 72
participants (144 eyes), who had received DSAEK in the first eye followed by DMEK
in the fellow eye. All the studies included adult participants where there was
evidence of FED and endothelial failure requiring a corneal transplant for the
treatment of visual impairment. We did not find any studies that included PBK.
The trials were published between 2011 and 2015, and we assessed them as high
risk of bias due to potential unknown confounding factors since DSAEK preceded
DMEK in all participants. Two studies reported results at 12 months, one at 6
months, and one between 6 and 24 months. At one year, using DMEK in cases of
endothelial failure may result in better BCVA compared with DSAEK (mean
difference (MD) -0.14, 95% confidence interval (CI) -0.18 to -0.10 logMAR, 4
studies, 140 eyes, low-certainty evidence). None of the participants had severe
visual loss (BCVA of 1.0 logMAR or more; very low-certainty evidence). Regarding
endothelial cell count data (4 studies, 134 eyes) it is hard to draw any
conclusions since two studies suggested no difference and the other two reported
that DMEK provides a higher cell density at one year (very low-certainty
evidence). No primary graft failure and only one graft rejection were recorded
over four studies (144 eyes) (very low-certainty evidence). The most common
complications reported were graft dislocations, which were recorded in one or two
out of 100 participants with DSAEK but were more common using DMEK, although this
difference could not be precisely estimated (risk ratio (RR) 5.40, 95% CI 1.51 to
19.3; 4 studies, 144 eyes, very low-certainty evidence). AUTHORS' CONCLUSIONS:
This review included studies conducted on people with corneal endothelium failure
due to FED for whom both DMEK and DSAEK can be considered, and found low
certainty evidence that DMEK provides some advantage in terms of final BCVA, at
the cost of more graft dislocations needing 're-bubbling' (very low-certainty of
evidence).
PMID- 29940079
TI - Constructing citizen engagement in health research priority-setting to attend to
dynamics of power and difference.
AB - Engaging citizens is vital to achieving people-centred health research. This
paper aims to put attention to dynamics of power and dynamics of difference back
at the centre of citizen engagement in health research priority-setting. Without
attention to power and difference, engagement can lead to presence without voice
and voice without influence, particularly for disadvantaged and marginalised
groups. By analysing six key bodies of literature, the paper first identifies the
different components of engagement-who initiates, for what purpose, who
participates, and how they participate-and the dynamics of power and dynamics of
difference relevant to them. For each component of engagement, the ethical
considerations relating to those dimensions of power and dimensions of difference
are characterised for the research priority-setting context and preliminary
guidance on how they might be addressed is provided. An initial framework
comprised of a series of questions reflecting these ethical considerations has
been developed for use by researchers and citizens when designing engagement
processes for research projects. Where researchers and citizens attend to the
framework's questions and then revise their priority-setting processes' design to
better represent diversity and mitigate power disparities, more inclusive citizen
engagement is promoted. Disadvantaged and marginalised groups are more likely to
be present and heard, which, in turn, will help generate research projects with
topics and questions that encompass and more accurately reflect their health
needs.
PMID- 29940081
TI - Ion-dependent metabolic responses of Vicia faba L. to salt stress.
AB - Salt-affected farmlands are increasingly burdened by chlorides, carbonates, and
sulfates of sodium, calcium, and magnesium. Intriguingly, the underlying
physiological processes are studied almost always under NaCl stress. Two faba
bean cultivars were subjected to low- and high-salt treatments of NaCl, Na2 SO4 ,
and KCl. Assimilation rate and leaf water vapor conductance were reduced to
approximately 25-30% without biomass reduction after 7 days salt stress, but this
did not cause severe carbon shortage. The equimolar treatments of Na+ , K+ , and
Cl- showed comparable accumulation patterns in leaves and roots, except for SO42-
which did not accumulate. To gain a detailed understanding of the effects caused
by the tested ion combinations, we performed nontargeted gas chromatography-mass
spectrometry-based metabolite profiling. Metabolic responses to various salts
were in part highly linearly correlated, but only a few metabolite responses were
common to all salts and in both cultivars. At high salt concentrations, only myo
inositol, allantoin, and glycerophosphoglycerol were highly significantly
increased in roots under all tested conditions. We discovered several metabolic
responses that were preferentially associated with the presence of Na+ , K+ , or
Cl- . For example, increases of leaf proline and decreases of leaf fumaric acid
and malic acid were apparently associated with Cl- accumulation.
PMID- 29940080
TI - Multispecies activity screening of microcin J25 mutants yields antimicrobials
with increased specificity toward pathogenic Salmonella species relative to human
commensal Escherichia coli.
AB - Modern large-scale agricultural practices that incorporate high density farming
with subtherapeutic antibiotic dosing are considered a major contributor to the
rise of antibiotic-resistant bacterial infections of humans with species of
Salmonella being a leading agriculture-based bacterial infection. Microcin J25, a
potent and highly stable antimicrobial peptide active against Enterobacteriaceae,
is a candidate antimicrobial against multiple Salmonella species. Emerging
evidence supports the hypothesis that the composition of the microbiota of the
gastrointestinal tract prevents a variety of diseases by preventing infectious
agents from proliferating. Reducing clearance of off-target bacteria may decrease
susceptibility to secondary infection. Of the Enterobacteriaceae susceptible to
microcin J25, Escherichia coli are the most abundant within the human gut. To
explore the modulation of specificity, a collection of 207 mutants encompassing
12 positions in both the ring and loop of microcin J25 was built and tested for
activity against Salmonella and E. coli strains. As has been found previously,
mutational tolerance of ring residues was lower than loop residues, with 22% and
51% of mutations, respectively, retaining activity toward at least one target
within the target organism test panel. The multitarget screening elucidated
increased mutational tolerance at position G2, G3, and G14 than previously
identified in panels composed of single targets. Multiple mutations conferred
differential response between the different targets. Examination of specificity
differences between mutants found that 30% showed significant improvements to
specificity toward any of the targets. Generation and testing of a combinatorial
library designed from the point-mutant study revealed that microcin J25I13T
reduces off-target activity toward commensal human-derived E. coli isolates by
81% relative to Salmonella enterica serovar Enteritidis. These in vitro
specificity improvements are likely to improve in vivo treatment efficacy by
reducing clearance of commensal bacteria in the gastrointestinal tract of hosts.
PMID- 29940082
TI - Rural Status, Suicide Ideation, and Telemental Health: Risk Assessment in a
Clinical Sample.
AB - OBJECTIVE: Individuals living in rural areas die by suicide at higher rates than
those living in metropolitan areas. Telemental health interventions provide rural
residing individuals with access to needed care. Identifying telemental health
clients at risk for suicide is an important task for clinicians and policymakers.
This study evaluated to what degree rural status and other demographic variables
predicted suicide ideation in clients seeking services at a telemental health
clinic. METHODS: Study participants included 457 low-income clients residing in
the medically underserved, geographically diverse Brazos Valley region of Texas.
Clients completed the patient health questionnaire during their initial
counseling appointment, which assessed depression severity and suicide ideation
in the 2 weeks prior to assessment. RESULTS: Suicide ideation was common among
telemental health clients, with approximately 40% of clients in all demographic
groups reporting some recent thoughts of suicide. Rates of suicide ideation did
not significantly differ by geographic designation (ie, rural/metropolitan
status), gender, or race/ethnicity. However, depression was a strong predictor of
recent suicide ideation. CONCLUSIONS: Telemental health programs can effectively
connect clinicians with rural residing clients who are otherwise isolated from
health care services. However, clinicians working in high-need, historically
underserved areas should be prepared to encounter a high prevalence of suicide
ideation and depression. In these regions, clinical and diagnostic features may
be better indicators of suicide ideation than demographic variables.
PMID- 29940083
TI - How much is enough? Effects of technical and biological replication on
metabarcoding dietary analysis.
AB - DNA metabarcoding is increasingly used in dietary studies to estimate diversity,
composition and frequency of occurrence of prey items. However, few studies have
assessed how technical and biological replication affect the accuracy of diet
estimates. This study addresses these issues using the European free-tailed bat
Tadarida teniotis, involving high-throughput sequencing of a small fragment of
the COI gene in 15 separate faecal pellets and a 15-pellet pool per each of 20
bats. We investigated how diet descriptors were affected by variability among (a)
individuals, (b) pellets of each individual and (c) PCRs of each pellet. In
addition, we investigated the impact of (d) analysing separate pellets vs. pellet
pools. We found that diet diversity estimates increased steadily with the number
of pellets analysed per individual, with seven pellets required to detect ~80% of
prey species. Most variation in diet composition was associated with differences
among individual bats, followed by pellets per individual and PCRs per pellet.
The accuracy of frequency of occurrence estimates increased with the number of
pellets analysed per bat, with the highest error rates recorded for prey consumed
infrequently by many individuals. Pools provided poor estimates of diet diversity
and frequency of occurrence, which were comparable to analysing a single pellet
per individual, and consistently missed the less common prey items. Overall, our
results stress that maximizing biological replication is critical in dietary
metabarcoding studies and emphasize that analysing several samples per individual
rather than pooled samples produce more accurate results.
PMID- 29940084
TI - Device-Level Photonic Memories and Logic Applications Using Phase-Change
Materials.
AB - Inspired by the great success of fiber optics in ultrafast data transmission,
photonic computing is being extensively studied as an alternative to replace or
hybridize electronic computers, which are reaching speed and bandwidth
limitations. Mimicking and implementing basic computing elements on photonic
devices is a first and essential step toward all-optical computers. Here, an
optical pulse-width modulation (PWM) switching of phase-change materials on an
integrated waveguide is developed, which allows practical implementation of
photonic memories and logic devices. It is established that PWM with low peak
power is very effective for recrystallization of phase-change materials, in terms
of both energy efficiency and process control. Using this understanding,
multilevel photonic memories with complete random accessibility are then
implemented. Finally, programmable optical logic devices are demonstrated
conceptually and experimentally, with logic "OR" and "NAND" achieved on just a
single integrated photonic phase-change cell. This study provides a practical and
elegant technique to optically program photonic phase-change devices for
computing applications.
PMID- 29940085
TI - Measurements of a 'normal vulva' in women aged 15-84: a cross-sectional
prospective single-centre study.
AB - OBJECTIVE: Accurate and detailed description of a 'normal vulva' is rare, even
though a few studies have dealt with the topic of normal measurements of parts of
the external female genitalia. This leads to a situation with a wide range of
existing diagnoses concerning 'normal' vulvar morphology. DESIGN: Cross-sectional
prospective single-centre study. SETTING: From August 2015 to April 2017, we
included 657 women in our gynaecological and uro-gynaecological outpatient clinic
of the Cantonal Hospital Lucerne. POPULATION OR SAMPLE: We recruited white women
aged 15-84 years. METHODS: Standardised defined measurements were taken of the
clitoral gland, distance from the base of the gland to the urethral orifice,
length of introitus, length of perineum, length of labia majora, and length and
width of labia minora. Furthermore, we recorded baseline characteristics. MAIN
OUTCOME MEASURES: The length of labia minora (r = -0.364, P < 0.001, n = 657) as
well as the length of the perineum (r = -0.095, P = 0.014, n = 657) are inversely
correlated with age. A positive correlation between body mass index and the
length of the labia majora (r = 0.150, P < 0.001, n = 657) and the length of the
introitus (r = 0.097, P = 0.014, n = 657) was found. RESULTS: We provide detailed
data on age-related dimensions and description of the external female genitalia
in a homogeneous group of white women. CONCLUSION: With our data, we present a
baseline for the appearance of a normal white vulva, which could be used to
establish standards for indications for gynaecological cosmetic surgery.
TWEETABLE ABSTRACT: This study presents data on the standard dimensions of the
external female genitalia and is, to our knowledge, the biggest cohort presented
on this topic by now.
PMID- 29940086
TI - Barriers and Pathways to Providing Long-Acting Reversible Contraceptives in
Massachusetts Community Health Centers: A Qualitative Exploration.
AB - CONTEXT: Structural barriers to the provision of long-acting reversible
contraceptive (LARC) methods at community health centers have been identified in
quantitative research, but the processes and behaviors by which center staff
respond to these barriers are poorly understood. METHODS: Focus group discussions
were conducted with clinical, support and administrative staff at three
Massachusetts community health centers between April 2014 and January 2015. The
centers were purposively selected to constitute a sample with diverse
characteristics. Overall, 57 individuals participated in seven focus groups. Data
were analyzed inductively using a modified grounded theory approach, and typical
pathways to obtaining LARC methods were identified. RESULTS: Community health
center staff provided contradictory descriptions of their facilities' protocols
and practices. Patients' pathways to obtaining LARC methods were idiosyncratic
and clinician-dependent, and resulted in patients' waiting between one week and
three months to receive their preferred method. Providers' individual comfort
with and perceived competence in contraceptive counseling often shaped patients'
pathways to care. Overall, staff did not consider same-day insertion of LARC
methods a feasible goal. Counseling protocols, insurance verification practices
and logistical challenges in ordering and stocking devices were identified as
major barriers to timely placement. CONCLUSIONS: Efforts to improve LARC
provision at community health centers should include the education of staff in
how expeditious placement constitutes clinical best practice and the
implementation of infrastructural changes to support staff in efficiently
counseling patients, scheduling placements and procuring LARC devices regardless
of patients' insurance coverage.
PMID- 29940087
TI - Evaluating genomic signatures of "the large X-effect" during complex speciation.
AB - The ubiquity of the "two rules of speciation"-Haldane's rule and the large X
effect-implies a general, special role for sex chromosomes in the evolution of
intrinsic postzygotic reproductive isolation. The recent proliferation of genome
scale analyses has revealed two further general observations: (a) complex
speciation involving some form of gene flow is not uncommon, and (b) sex
chromosomes in male- and in female-heterogametic taxa tend to show elevated
differentiation relative to autosomes. Together, these observations are
consistent with speciation histories in which population genetic differentiation
at autosomal loci is reduced by gene flow while natural selection against hybrid
incompatibilities renders sex chromosomes relatively refractory to gene flow.
Here, I summarize multilocus population genetic and population genomic evidence
for greater differentiation on the X (or Z) vs. the autosomes and consider the
possible causes. I review common population genetic circumstances involving no
selection and/or no interspecific gene flow that are nevertheless expected to
elevate differentiation on sex chromosomes relative to autosomes. I then review
theory for why large X-effects exist for hybrid incompatibilities and, more
generally, for loci mediating local adaptation. The observed levels of sex
chromosome vs. autosomal differentiation, in many cases, appear consistent with
simple explanations requiring neither large X-effects nor gene flow. Discerning
signatures of large X-effects during complex speciation will therefore require
analyses that go beyond chromosome-scale summaries of population genetic
differentiation, explicitly test for differential introgression, and/or integrate
experimental genetic data.
PMID- 29940088
TI - Nonlinear Unmixing of Hyperspectral Datasets for the Study of Painted Works of
Art.
AB - Nonlinear unmixing of hyperspectral reflectance data is one of the key problems
in quantitative imaging of painted works of art. The approach presented is to
interrogate a hyperspectral image cube by first decomposing it into a set of
reflectance curves representing pure basis pigments and second to estimate the
scattering and absorption coefficients of each pigment in a given pixel to
produce estimates of the component fractions. This two-step algorithm uses a deep
neural network to qualitatively identify the constituent pigments in any unknown
spectrum and, based on the pigment(s) present and Kubelka-Munk theory to estimate
the pigment concentration on a per-pixel basis. Using hyperspectral data acquired
on a set of mock-up paintings and a well-characterized illuminated folio from the
15th century, the performance of the proposed algorithm is demonstrated for
pigment recognition and quantitative estimation of concentration.
PMID- 29940090
TI - Segmental bone replacement via patient-specific, three-dimensional printed
bioresorbable graft substitutes and their use as templates for the culture of
mesenchymal stem cells under mechanical stimulation at various frequencies.
AB - The treatment of large segmental bone defects remains a challenge as infection,
delayed union, and nonunion are common postoperative complications. A three
dimensional printed bioresorbable and physiologically load-sustaining graft
substitute was developed to mimic native bone tissue for segmental bone repair.
Fabricated from polylactic acid, this graft substitute is novel as it is readily
customizable to accommodate the particular size and location of the segmental
bone of the patient to be replaced. Inspired by the structure of the native bone
tissue, the graft substitute exhibits a gradient in porosity and pore size in the
radial direction and exhibit mechanical properties similar to those of the native
bone tissue. The graft substitute can serve as a template for tissue constructs
via seeding with stem cells. The biocompatibility of such templates was tested
under in vitro conditions using a dynamic culture of human mesenchymal stem
cells. The effects of the mechanical loading of cell-seeded templates under in
vitro conditions were assessed via subjecting the tissue constructs to 28 days of
daily mechanical stimulation. The frequency of loading was found to have a
significant effect on the rate of mineralization, as the alkaline phosphatase
activity and calcium deposition were determined to be particularly high at the
typical walking frequency of 2 Hz, suggesting that mechanical stimulation plays a
significant role in facilitating the healing process of bone defects. Utilization
of such patient-specific and biocompatible graft substitutes, coupled with
patient's bone marrow cells seeded and exposed to mechanical stimulation of 2 Hz
have the potential of reducing significant volumes of cadaveric tissue required,
improving long-term graft stability and incorporation, and alleviating financial
burdens associated with delayed or failed fusions of long bone defects.
PMID- 29940089
TI - Abnormal vaginal bleeding in women of reproductive age treated with edoxaban or
warfarin for venous thromboembolism: a post hoc analysis of the Hokusai-VTE
study.
AB - OBJECTIVE: To investigate the characteristics and outcome of abnormal vaginal
bleeding in women receiving edoxaban or warfarin for treatment of venous
thromboembolism (VTE). DESIGN AND SETTING: Post hoc analysis of the Hokusai-VTE
study, a multicentre, randomised, double-blind trial comparing edoxaban with
warfarin for acute symptomatic VTE. POPULATION: Women below 50 years receiving
edoxaban or warfarin for treatment of VTE. METHODS: We collected data on
diagnostic measures, treatment, and clinical outcome of abnormal vaginal bleeding
events. MAIN OUTCOME MEASURES: Occurrence of major and clinically relevant
nonmajor (CRNM) abnormal vaginal bleeding events. RESULTS: In all, 628 women aged
under 50 years were treated with edoxaban and 665 with warfarin. The rate of
abnormal vaginal bleeding was 15/100 person-years (py) (95% CI 11-19) in women
receiving edoxaban and 9/100 py (95% CI 6-12) in the warfarin group (hazard
ratio: 1.7, 95% CI 1.1-2.5). Major abnormal vaginal bleeding occurred in eight
(1.3%) women on edoxaban and in three (0.9%) women receiving warfarin [odds ratio
(OR) 2.8; 95% CI 0.8-10.8], and CRNM abnormal vaginal bleeding occurred in 53
(8.4%) women treated with edoxaban and in 37 (5.6%) on warfarin therapy (OR 1.6,
95% CI 1.0-2.4). Over 85% of all vaginal bleeds were characterised by heavy
menstrual bleeding. Major bleeds frequently required treatment, and in more than
75% of patients anticoagulant therapy was adjusted. The severity of clinical
presentation and course of major and CRNM bleeds was mild in most patients.
CONCLUSIONS: Abnormal vaginal bleeding occurred more frequently in women treated
with edoxaban than with warfarin. Reassuringly, most events could be managed
conservatively and had a mild outcome. TWEETABLE ABSTRACT: Abnormal vaginal
bleeding occurred more frequently in women treated with edoxaban than with
warfarin.
PMID- 29940091
TI - In-hospital and subsequent mortality among lung transplant recipients with a
prolonged initial hospitalization.
AB - The care of lung transplant recipients with prolonged index hospitalizations can
be ethically complex, with conflicts arising over whether the expected outcomes
justify ongoing intensive interventions. There are limited data to guide these
conversations. The objective of this study was to evaluate survival to discharge
for lung transplant recipients based on length of stay (LOS). This was a
retrospective cohort study of adult lung transplant recipients in the Scientific
Registry of Transplant Recipients. For each day of the index hospitalization the
mortality rate among patients who survived to that length of stay or longer was
calculated. Post-discharge survival was compared in those with and without a
prolonged hospitalization (defined as the 97th percentile [>90 days]). Among the
19 250 included recipients, the index hospitalization mortality was 5.4%.
Posttransplant stroke and need for dialysis were the strongest predictors of
index hospitalization mortality. No individual or combination of available risk
factors, however, was associated with inpatient mortality consistently above 50%.
Recipients with >90 day index hospitalization had a 28.8% subsequent inpatient
mortality. Their 1, 3 and 5 year survival following discharge was 53%, 26%, and
16%. These data provide additional context to goals of care conversations for
transplant recipients with prolonged index hospitalizations.
PMID- 29940092
TI - An association between differential expression and genetic divergence in the
Patagonian olive mouse (Abrothrix olivacea).
AB - Recent molecular studies have found striking differences between desert-adapted
species and model mammals regarding water conservation. In particular, aquaporin
4, a classical gene involved in water regulation of model species, is absent or
not expressed in the kidneys of desert-adapted species. To further understand the
molecular response to water availability, we studied the Patagonian olive mouse
Abrothrix olivacea, a species with an unusually broad ecological tolerance that
exhibits a great urine concentration capability. The species is able to occupy
both the arid Patagonian steppe and the Valdivian and Magellanic forests. We
sampled 95 olive mouse specimens from four localities (two in the steppe and two
in the forests) and analysed both phenotypic variables and transcriptomic data to
investigate the response of this species to the contrasting environmental
conditions. The relative size of the kidney and the ratio of urine to plasma
concentrations were, as expected, negatively correlated with annual rainfall.
Expression analyses uncovered nearly 3,000 genes that were differentially
expressed between steppe and forest samples and indicated that this species
resorts to the "classical" gene pathways for water regulation. Differential
expression across biomes also involves genes that involved in immune and
detoxification functions. Overall, genes that were differentially expressed
showed a slight tendency to be more divergent and to display an excess of
intermediate allele frequencies, relative to the remaining loci. Our results
indicate that both differential expression in pathways involved in water
conservation and geographical allelic variation are important in the occupation
of contrasting habitats by the Patagonian olive mouse.
PMID- 29940093
TI - Postoperative Pain Management Practice at Teaching Hospitals in Jordan.
PMID- 29940094
TI - SPQ (Self Promoter Questionnaire) or Spec (Self Promotion Evaluator Collector).
AB - Healing hospitals have evolved into business companies (institutions). Therefore,
the need arises to evaluate the care rendered not only for the sake of adequacy
of healing among patients but also for the sake of self-promotions to ensure
returning customers. This letter brings forth ourpost-hoc objective method that
can be an answer and/or replacement to pre-hoc subjective scoring of services by
Net Promoter Score(r) or The National Health Service Friends and Family Test.
Both the abovementioned scores work on the flawed avenue based on the
satisfaction perceivedimmediate post-care/service by consumers (employees or
patients). The reason for this flaw is that these scores do NOT look into whether
the scored satisfactions and consequent presumptions actually shape into direct
reality for the evaluated institutions. Herein our SPQ: Self
PromoterQuestionnaire or SPEC: Self Promotion Evaluator Collector comes in handy.
This yet to be validated objective assessment of institutions definitely looks
encouraging.
PMID- 29940095
TI - Efficacy of Cervical Epidural Steroid Injections for Cervical Radiculopathy.
PMID- 29940096
TI - Erratum: Anesthetic considerations for the neonate with tracheoesophageal
fistula.
PMID- 29940098
TI - Cobalt Disulfide Nanoparticles Embedded in Porous Carbonaceous Micro-Polyhedrons
Interlinked by Carbon Nanotubes for Superior Lithium and Sodium Storage.
AB - Transition metal sulfides are appealing electrode materials for lithium and
sodium batteries owing to their high theoretical capacity. However, they are
commonly characterized by rather poor cycling stability and low rate capability.
Herein, we investigate CoS2, serving as a model compound. We synthesized a porous
CoS2/C micro-polyhedron composite entangled in a carbon-nanotube-based network
(CoS2-C/CNT), starting from zeolitic imidazolate frameworks-67 as a single
precursor. Following an efficient two-step synthesis strategy, the obtained CoS2
nanoparticles are uniformly embedded in porous carbonaceous micro-polyhedrons,
interwoven with CNTs to ensure high electronic conductivity. The CoS2-C/CNT
nanocomposite provides excellent bifunctional energy storage performance,
delivering 1030 mAh g-1 after 120 cycles and 403 mAh g-1 after 200 cycles (at 100
mA g-1) as electrode for lithium-ion (LIBs) and sodium-ion batteries (SIBs),
respectively. In addition to these high capacities, the electrodes show
outstanding rate capability and excellent long-term cycling stability with a
capacity retention of 80% after 500 cycles for LIBs and 90% after 200 cycles for
SIBs. In situ X-ray diffraction reveals a significant contribution of the
partially graphitized carbon to the lithium and at least in part also for the
sodium storage and the report of a two-step conversion reaction mechanism of
CoS2, eventually forming metallic Co and Li2S/Na2S. Particularly the lithium
storage capability at elevated (dis-)charge rates, however, appears to be
substantially pseudocapacitive, thus benefiting from the highly porous nature of
the nanocomposite.
PMID- 29940097
TI - Distinguishing Specific and Nonspecific Complexes of Alkyladenine DNA
Glycosylase.
AB - Human alkyladenine DNA glycosylase (AAG) recognizes many alkylated and deaminated
purine lesions and excises them to initiate the base excision DNA repair pathway.
AAG employs facilitated diffusion to rapidly scan nonspecific sites and locate
rare sites of damage. Nonspecific DNA binding interactions are critical to the
efficiency of this search for damage, but little is known about the binding
footprint or the affinity of AAG for nonspecific sites. We used biochemical and
biophysical approaches to characterize the binding of AAG to both undamaged and
damaged DNA. Although fluorescence anisotropy is routinely used to study DNA
binding, we found unexpected complexities in the data for binding of AAG to DNA.
Systematic comparison of different fluorescent labels and different lengths of
DNA allowed binding models to be distinguished and demonstrated that AAG can bind
with high affinity and high density to nonspecific DNA. Fluorescein-labeled DNA
gave the most complex behavior but also showed the greatest potential to
distinguish specific and nonspecific binding modes. We suggest a unified model
that is expected to apply to many DNA binding proteins that exhibit affinity for
nonspecific DNA. Although AAG strongly prefers to excise lesions from duplex DNA,
nonspecific binding is comparable for single- and double-stranded nonspecific
sites. The electrostatically driven binding of AAG to small DNA sites (~5
nucleotides of single-stranded and ~6 base pairs of duplex) facilitates the
search for DNA damage in chromosomal DNA, which is bound by nucleosomes and other
proteins.
PMID- 29940099
TI - Recombinant Spider Silk Functionalized Silkworm Silk Matrices as Potential
Bioactive Wound Dressings and Skin Grafts.
AB - Silk is considered to be a potential biomaterial for a wide number of biomedical
applications. Silk fibroin (SF) can be retrieved in sufficient quantities from
the cocoons produced by silkworms. While it is easy to formulate into scaffolds
with favorable mechanical properties, the natural SF does not contain bioactive
functions. Spider silk proteins, on the contrary, can be produced in fusion with
bioactive protein domains, but the recombinant procedures are expensive, and
large-scale production is challenging. We combine the two types of silk to
fabricate affordable, functional tissue-engineered constructs for wound-healing
applications. Nanofibrous mats and microporous scaffolds made of natural silkworm
SF are used as a bulk material that are top-coated with the recombinant spider
silk protein (4RepCT) in fusion with a cell-binding motif, antimicrobial
peptides, and a growth factor. For this, the inherent silk properties are
utilized to form interactions between the two silk types by self-assembly. The
intended function, that is, improved cell adhesion, antimicrobial activity, and
growth factor stimulation, could be demonstrated for the obtained functionalized
silk mats. As a skin prototype, SF scaffolds coated with functionalized silk are
cocultured with multiple cell types to demonstrate formation of a bilayered
tissue construct with a keratinized epidermal layer under in vitro conditions.
The encouraging results support this strategy of fabrication of an affordable
bioactive SF-spider silk-based biomaterial for wound dressings and skin
substitutes.
PMID- 29940100
TI - SmgGDS-607 Regulation of RhoA GTPase Prenylation Is Nucleotide-Dependent.
AB - Protein prenylation involves the attachment of a hydrophobic isoprenoid moiety to
the C-terminus of proteins. Several small GTPases, including members of the Ras
and Rho subfamilies, require prenylation for their normal and pathological
functions. Recent work has suggested that SmgGDS proteins regulate the
prenylation of small GTPases in vivo. Using RhoA as a representative small
GTPase, we directly test this hypothesis using biochemical assays and present a
mechanism describing the mode of prenylation regulation. SmgGDS-607 completely
inhibits RhoA prenylation catalyzed by protein geranylgeranyltransferase I
(GGTase-I) in an in vitro radiolabel incorporation assay. SmgGDS-607 inhibits
prenylation by binding to and blocking access to the C-terminal tail of the small
GTPase (substrate sequestration mechanism) rather than via inhibition of the
prenyltransferase activity. The reactivity of GGTase-I with RhoA is unaffected by
addition of nucleotides. In contrast, the affinity of SmgGDS-607 for RhoA varies
with the nucleotide bound to RhoA; SmgGDS-607 has a higher affinity for RhoA-GDP
compared to RhoA-GTP. Consequently, the prenylation blocking function of SmgGDS
607 is regulated by the bound nucleotide. This work provides mechanistic insight
into a novel pathway for the regulation of small GTPase protein prenylation by
SmgGDS-607 and demonstrates that peptides are a good mimic for full-length
proteins when measuring GGTase-I activity.
PMID- 29940102
TI - Direct Pathway Cloning Combined with Sequence- and Ligation-Independent Cloning
for Fast Biosynthetic Gene Cluster Refactoring and Heterologous Expression.
AB - The need for new pharmacological lead structures, especially against drug
resistances, has led to a surge in natural product research and discovery. New
biosynthetic gene cluster capturing methods to efficiently clone and
heterologously express natural product pathways have thus been developed. Direct
pathway cloning (DiPaC) is an emerging synthetic biology strategy that utilizes
long-amplification PCR and HiFi DNA assembly for the capture and expression of
natural product biosynthetic gene clusters. Here, we have further streamlined
DiPaC by reducing cloning time and reagent costs by utilizing T4 DNA polymerase
(sequence- and ligation-independent cloning, SLIC) for gene cluster capture. As a
proof of principle, the majority of the cyanobacterial hapalosin gene cluster was
cloned as a single piece (23 kb PCR product) using this approach, and predicted
transcriptional terminators were removed by simultaneous pathway refactoring,
leading to successful heterologous expression. The complementation of DiPaC with
SLIC depicts a time and cost-efficient method for simple capture and expression
of new natural product pathways.
PMID- 29940101
TI - Verteporfin-Loaded Poly(ethylene glycol)-Poly(beta-amino ester)-Poly(ethylene
glycol) Triblock Micelles for Cancer Therapy.
AB - Amphiphilic polymers can be used to form micelles to deliver water-insoluble
drugs. A biodegradable poly(ethylene glycol) (PEG)-poly(beta-amino ester) (PBAE)
PEG triblock copolymer was developed that is useful for drug delivery. It was
shown to successfully encapsulate and pH-dependently release a water-insoluble,
small molecule anticancer drug, verteporfin. PEG-PBAE-PEG micelle morphology was
also controlled through variations to the hydrophobicity of the central PBAE
block of the copolymer in order to evade macrophage uptake. Spherical micelles
were 50 nm in diameter, while filamentous micelles were 31 nm in width with an
average aspect ratio of 20. When delivered to RAW 264.7 mouse macrophages,
filamentous micelles exhibited a 89% drop in cellular uptake percentage and a 5.6
fold drop in normalized geometric mean cellular uptake compared to spherical
micelles. This demonstrates the potential of high-aspect-ratio, anisotropically
shaped PEG-PBAE-PEG micelles to evade macrophage-mediated clearance. Both
spherical and filamentous micelles also showed therapeutic efficacy in human
triple-negative breast cancer and small cell lung cancer cells without requiring
photodynamic therapy to achieve an anticancer effect. Both spherical and
filamentous micelles were more effective in killing lung cancer cells than breast
cancer cells at equivalent verteporfin concentrations, while spherical micelles
were shown to be more effective than filamentous micelles against both cancer
cells. Spherical and filamentous micelles at 5 and 10 MUM respective verteporfin
concentration resulted in 100% cell killing of lung cancer cells, but both
micelles required a higher verteporfin concentration of 20 MUM to kill breast
cancer cells at the levels of 80% and 50% respectively. This work demonstrates
the potential of PEG-PBAE-PEG as a biodegradable, anisotropic drug delivery
system as well as the in vitro use of verteporfin-loaded micelles for cancer
therapy.
PMID- 29940103
TI - Donor-Acceptor-Collector Ternary Crystalline Films for Efficient Solid-State
Photon Upconversion.
AB - It is pivotal to achieve efficient triplet-triplet annihilation based photon
upconversion (TTA-UC) in the solid-state for enhancing potentials of renewable
energy production devices. However, the UC efficiency of solid materials is
largely limited by low fluorescence quantum yields that originate from the
aggregation of TTA-UC chromophores and also by severe back energy transfer from
the acceptor singlet state to the singlet state of the triplet donor in the
condensed state. In this work, to overcome these issues, we introduce a highly
fluorescent singlet energy collector as the third component of donor-doped
acceptor crystalline films, in which dual energy migration, i.e., triplet energy
migration for TTA-UC and succeeding singlet energy migration for transferring
energy to a collector, takes place. To demonstrate this scheme, a highly
fluorescent singlet energy collector was added as the third component of donor
doped acceptor crystalline films. An anthracene-based acceptor containing alkyl
chains and a carboxylic moiety is mixed with the triplet donor Pt(II)
octaethylporphyrin (PtOEP) and the energy collector 2,5,8,11-tetra- tert
butylperylene (TTBP) in solution, and simple spin-coating of the mixed solution
gives acceptor films of nanofibrous crystals homogeneously doped with PtOEP and
TTBP. Interestingly, delocalized singlet excitons in acceptor crystals are found
to diffuse effectively over the distance of ~37 nm. Thanks to this high
diffusivity, only 0.5 mol % of doped TTBP can harvest most of the singlet
excitons, which successfully doubles the solid-state fluorescent quantum yield of
acceptor/TTBP blend films to 76%. Furthermore, since the donor PtOEP and the
collector TTBP are separately isolated in the nanofibrous acceptor crystals, the
singlet back energy transfer from the collector to the donor is effectively
avoided. Such efficient singlet energy collection and inhibited back energy
transfer processes result in a large increase of UC efficiency up to 9.0%,
offering rational design principles toward ultimately efficient solid-state
upconverters.
PMID- 29940104
TI - Structural Insights into the Regulation of Staphylococcus aureus
Phosphofructokinase by Tetramer-Dimer Conversion.
AB - Most reported bacterial phosphofructokinases (Pfks) are tetramers that exhibit
activity allosterically regulated via conformational changes between the R and T
states. We report that the Pfk from Staphylococcus aureus NCTC 8325 ( SaPfk)
exists as both an active tetramer and an inactive dimer in solution. Multiple
effectors, including pH, ADP, ATP, and adenylyl-imidodiphosphate (AMP-PNP), cause
equilibrium shifts from the tetramer to dimer, whereas the substrate F6P
stabilizes SaPfk tetrameric assembly. Crystal structures of SaPfk in complex with
different ligands and biochemical analysis reveal that the flexibility of the
Gly150-Leu151 motif in helix alpha7 plays a role in tetramer-dimer conversion.
Thus, we propose a molecular mechanism for allosteric regulation of bacterial Pfk
via conversion between the tetramer and dimer in addition to the well
characterized R-state/T-state mechanism.
PMID- 29940105
TI - Allosteric Activation Shifts the Rate-Limiting Step in a Short-Form ATP
Phosphoribosyltransferase.
AB - Short-form ATP phosphoribosyltransferase (ATPPRT) is a hetero-octameric
allosteric enzyme comprising four catalytic subunits (HisGS) and four regulatory
subunits (HisZ). ATPPRT catalyzes the Mg2+-dependent condensation of ATP and 5
phospho-alpha-d-ribosyl-1-pyrophosphate (PRPP) to generate N1-(5-phospho-beta-d
ribosyl)-ATP (PRATP) and pyrophosphate, the first reaction of histidine
biosynthesis. While HisGS is catalytically active on its own, its activity is
allosterically enhanced by HisZ in the absence of histidine. In the presence of
histidine, HisZ mediates allosteric inhibition of ATPPRT. Here, initial velocity
patterns, isothermal titration calorimetry, and differential scanning fluorimetry
establish a distinct kinetic mechanism for ATPPRT where PRPP is the first
substrate to bind. AMP is an inhibitor of HisGS, but steady-state kinetics and
31P NMR spectroscopy demonstrate that ADP is an alternative substrate.
Replacement of Mg2+ by Mn2+ enhances catalysis by HisGS but not by the
holoenzyme, suggesting different rate-limiting steps for nonactivated and
activated enzyme forms. Density functional theory calculations posit an SN2-like
transition state stabilized by two equivalents of the metal ion. Natural bond
orbital charge analysis points to Mn2+ increasing HisGS reaction rate via more
efficient charge stabilization at the transition state. High solvent viscosity
increases HisGS's catalytic rate, but decreases the hetero-octamer's, indicating
that chemistry and product release are rate-limiting for HisGS and ATPPRT,
respectively. This is confirmed by pre-steady-state kinetics, with a burst in
product formation observed with the hetero-octamer but not with HisGS. These
results are consistent with an activation mechanism whereby HisZ binding leads to
a more active conformation of HisGS, accelerating chemistry beyond the product
release rate.
PMID- 29940106
TI - Selective Wavelength Plasmonic Flash Light Welding of Silver Nanowires for
Transparent Electrodes with High Conductivity.
AB - In this work, silver nanowires (AgNWs) printed on a polyethylene terephthalate
substrate using a bar coater were welded via selective wavelength plasmonic flash
light irradiation. To achieve high electrical conductivity and transparent
characteristics, the wavelength of the flash white light was selectively chosen
and irradiated by using high-pass, low-pass, and band-pass filters. The flash
white light irradiation conditions such as on-time, off-time, and number of
pulses were also optimized. The wavelength range (400-500 nm) corresponding to
the plasmonic wavelength of the AgNW could efficiently weld the AgNW films and
enhance its conductivity. To carry out in-depth study of the welding phenomena
with respect to wavelength, a multiphysics COMSOL simulation was conducted. The
welded AgNW films under selective plasmonic flash light welding conditions showed
the lowest sheet resistance (51.275 Omega/sq) and noteworthy transmittance
(95.3%). Finally, the AgNW film, which was welded by selective wavelength
plasmonic flash light with optical filters, was successfully used to make a large
area transparent heat film and dye-sensitized solar cells showing superior
performances.
PMID- 29940107
TI - Aqueous Ion Trapping and Transport in Graphene-Embedded 18-Crown-6 Ether Pores.
AB - Using extensive room-temperature molecular dynamics simulations, we investigate
selective aqueous cation trapping and permeation in graphene-embedded 18-crown-6
ether pores. We show that in the presence of suspended water-immersed crown
porous graphene, K+ ions rapidly organize and trap stably within the pores, in
contrast with Na+ ions. As a result, significant qualitative differences in
permeation between ionic species arise. The trapped ion occupancy and permeation
behaviors are shown to be highly voltage-tunable. Interestingly, we demonstrate
the possibility of performing conceptually straightforward ion-based logical
operations resulting from controllable membrane charging by the trapped ions. In
addition, we show that ionic transistors based on crown-porous graphene are
possible, suggesting utility in cascaded ion-based logic circuitry. Our results
indicate that in addition to numerous possible applications of graphene-embedded
crown ether nanopores, including deionization, ion sensing/sieving, and energy
storage, simple ion-based logical elements may prove promising as building blocks
for reliable nanofluidic computational devices.
PMID- 29940108
TI - How To Excite Nuclear Wavepackets into Electronically Degenerate States in Spin
Vibronic Quantum Dynamics Simulations.
AB - The excited-state dynamics of two functional Fe-carbene complexes, [Fe(bmip)2]2+
(bmip = 2,6-bis(3-methyl-imidazole-1-ylidene)-pyridine) and [Fe(btbip)2]2+ (btbip
= 2,6-bis(3- tert-butyl-imidazole-1-ylidene)pyridine), are studied using the spin
vibronic model. In contrast to the usual projection of the ground state nuclear
wave function onto an excited state surface, the dynamics are initiated by an
explicit interaction term between the external time-dependent electric field
(laser pulse) and the transition dipole moment of the molecule. The results show
that the spin-vibronic model, as constructed directly from electronic structure
calculations, exhibits erroneous, polarization-dependent relaxation dynamics
stemming from artificial interference of coupled relaxation pathways. This is due
to the lack of rotational invariance in the description of excitation into
degenerate states. We introduce and discuss a correction using the spherical
basis and complex transition dipole moments. This modification in the interaction
Hamiltonian leads to rotationally invariant excitation and produces polarization
independent population dynamics.
PMID- 29940109
TI - Dependence of the Formation of Tau and Abeta Peptide Mixed Aggregates on the
Secondary Structure of the N-Terminal Region of Abeta.
AB - One of the hallmarks of Alzheimer's disease is the formation of aggregates of the
tau protein, a process that can be facilitated by the presence of fibrils formed
by the amyloid beta peptide (Abeta). However, the mechanism that triggers tau
aggregation is still a matter of debate. The effect of Abeta40 fibrils on the
aggregation of the repeat domain of tau (TauRD) is investigated here by employing
coarse-grained molecular dynamics simulations. The results indicate that the
repeat domain of tau has a high affinity for Abeta40 fibrils, with the
261GSTENLK267 fragment of tau driving TauRD toward the 16KLVFFA21 fragment in
Abeta40. Monomeric Abeta40, in which the 16KLVFFA21 fragment is rarely found in
an extended conformation (as in the fibril), has a low affinity for the TauRD,
indicating that the ability of Abeta40 fibrils to bind to the TauRD depends on
the 16KLVFFA21 fragment of Abeta adopting an extended conformation.
PMID- 29940110
TI - Nucleoside Analogue-Based Supramolecular Nanodrugs Driven by Molecular
Recognition for Synergistic Cancer Therapy.
AB - The utilization of nanotechnology for the delivery of a wide range of anticancer
drugs has the potential to reduce adverse effects of free drugs and improve the
anticancer efficacy. However, carrier materials and/or chemical modifications
associated with drug delivery make it difficult for nanodrugs to achieve clinical
translation and final Food and Drug Administration (FDA) approvals. We have
discovered a molecular recognition strategy to directly assemble two FDA-approved
small-molecule hydrophobic and hydrophilic anticancer drugs into well-defined,
stable nanostructures with high and quantitative drug loading. Molecular dynamics
simulations demonstrate that purine nucleoside analogue clofarabine and folate
analogue raltitrexed can self-assemble into stable nanoparticles through
molecular recognition. In vitro studies exemplify how the clofarabine:raltitrexed
nanoparticles could greatly improve synergistic combination effects by arresting
more G1 phase of the cell cycle and reducing intracellular deoxynucleotide pools.
More importantly, the nanodrugs increase the blood retention half-life of the
free drugs, improve accumulation of drugs in tumor sites, and promote the
synergistic tumor suppression property in vivo.
PMID- 29940111
TI - Exploiting Coordinate Scaling Relations To Accelerate Exact Exchange
Calculations.
AB - Exact exchange is an important constituent in many state-of-the-art
approximations to the exchange-correlation (xc) functional of Kohn-Sham DFT.
However, its evaluation can be computationally intensive, which can be
particularly prohibitive in DFT-based molecular dynamics (MD) simulations, often
restricted to semilocal functionals. We derive a scheme based on the formal
coordinate scaling properties of the exact xc functional that allows for a
substantial reduction of the cost of the evaluation of both the exact exchange
energy and potential. We show that within a plane-wave/pseudopotential framework,
excellent accuracy is retained, while speed ups from up to ~6 can be reached. The
coordinate scaling thus accelerates hybrid-functional-based first-principles MD
simulations by nearly one order of magnitude.
PMID- 29940112
TI - Isolated Fe(III)-O Sites Catalyze the Hydrogenation of Acetylene in Ethylene
Flows under Front-End Industrial Conditions.
AB - The search for simple, earth-abundant, cheap, and nontoxic metal catalysts able
to perform industrial hydrogenations is a topic of interest, transversal to many
catalytic processes. Here, we show that isolated FeIII-O sites on solids are able
to dissociate and chemoselectively transfer H2 to acetylene in an industrial
process. For that, a novel, robust, and highly crystalline metal-organic
framework (MOF), embedding FeIII-OH2 single sites within its pores, was prepared
in multigram scale and used as an efficient catalyst for the hydrogenation of 1%
acetylene in ethylene streams under front-end conditions. Cutting-edge X-ray
crystallography allowed the resolution of the crystal structure and snapshotted
the single-atom nature of the catalytic FeIII-O site. Translation of the active
site concept to even more robust and inexpensive titania and zirconia supports
enabled the industrially relevant hydrogenation of acetylene with similar
activity to the Pd-catalyzed process.
PMID- 29940113
TI - Fabrication of Large-Area Arrays of Vertically Aligned Gold Nanorods.
AB - Anisotropic nanoparticles, such as nanorods and nanoprisms, enable packing of
complex nanoparticle structures with different symmetry and assembly orientation,
which result in unique functions. Despite previous extensive efforts, formation
of large areas of oriented or aligned nanoparticle structures still remains a
great challenge. Here, we report fabrication of large-area arrays of vertically
aligned gold nanorods (GNR) through a controlled evaporation deposition process.
We began with a homogeneous suspension of GNR and surfactants prepared in water.
During drop casting on silicon substrates, evaporation of water progressively
enriched the concentrations of the GNR suspension, which induces the balance
between electrostatic interactions and entropically driven depletion attraction
in the evaporating solution to produce large-area arrays of self-assembled GNR on
the substrates. Electron microscopy characterizations revealed the formation of
layers of vertically aligned GNR arrays that consisted of hexagonally close
packed GNR in each layer. Benefiting from the close-packed GNR arrays and their
smooth topography, the GNR arrays exhibited a surface-enhanced Raman scattering
(SERS) signal for molecular detection at a concentration as low as 10-15 M.
Because of the uniformity in large area, the GNR arrays exhibited exceptional
detecting reproducibility and operability. This method is scalable and cost
effective and could lead to diverse packing structures and functions by variation
of guest nanoparticles in the suspensions.
PMID- 29940114
TI - Three-Dimensional in Situ Electron-Beam Lithography Using Water Ice.
AB - Three-dimensional (3D) nanofabrication techniques are of paramount importance in
nanoscience and nanotechnology because they are prerequisites to realizing
complex, compact, and functional 3D nanodevices. Although several 3D
nanofabrication methods have been proposed and developed in recent years, it is
still a formidable challenge to achieve a balance among resolution, accuracy,
simplicity, and adaptability. Here, we propose a 3D nanofabrication method based
on electron-beam lithography using ice resists (iEBL) and fabricate 3D
nanostructures by stacking layered structures and those with dose-modulated
exposure, respectively. The entire process of 3D nanofabrication is realized in
one vacuum system by skipping the spin-coating and developing steps required for
commonly used resists. This needs far fewer processing steps and is contamination
free compared with conventional methods. With in situ alignment and correction in
the iEBL process, a pattern resolution of 20 nm and an alignment error below 100
nm can be steadily achieved. This 3D nanofabrication technique using ice thus
shows great potential in the fabrication of complicated 3D nanodevices.
PMID- 29940115
TI - Discovery of Janus Kinase 2 (JAK2) and Histone Deacetylase (HDAC) Dual Inhibitors
as a Novel Strategy for the Combinational Treatment of Leukemia and Invasive
Fungal Infections.
AB - Clinically, leukemia patients often suffer from the limited efficacy of
chemotherapy and high risks of infection by invasive fungal pathogens. Herein, a
novel therapeutic strategy was developed in which a small molecule can
simultaneously treat leukemia and invasive fungal infections (IFIs). Novel Janus
kinase 2 (JAK2) and histone deacetylase (HDAC) dual inhibitors were identified to
possess potent anti-proliferative activity toward hematological cell lines and
excellent synergistic effects with fluconazole to treat resistant Candida
albicans infections. In particular, compound 20a, a highly active and selective
JAK2/HDAC6 dual inhibitor, showed excellent in vivo antitumor efficacy in several
acute myeloid leukemia (AML) models and synergized with fluconazole for the
treatment of resistant C. albicans infections. This study highlights the
therapeutic potential of JAK2/HDAC dual inhibitors in treating AML and IFIs and
provides an efficient strategy for multitargeting drug discovery.
PMID- 29940116
TI - Magnetically Sensitive Radical Photochemistry of Non-natural Flavoproteins.
AB - It is a remarkable fact that ~50 MUT magnetic fields can alter the rates and
yields of certain free-radical reactions and that such effects might be the basis
of the light-dependent ability of migratory birds to sense the direction of the
Earth's magnetic field. The most likely sensory molecule at the heart of this
chemical compass is cryptochrome, a flavin-containing protein that undergoes
intramolecular, blue-light-induced electron transfer to produce magnetically
sensitive radical pairs. To learn more about the factors that control the
magnetic sensitivity of cryptochromes, we have used a set of de novo designed
protein maquettes that self-assemble as four-alpha-helical proteins incorporating
a single tryptophan residue as an electron donor placed approximately 0.6, 1.1,
or 1.7 nm away from a covalently attached riboflavin as chromophore and electron
acceptor. Using a specifically developed form of cavity ring-down spectroscopy,
we have characterized the photochemistry of these designed flavoprotein maquettes
to determine the identities and kinetics of the transient radicals responsible
for the magnetic field effects. Given the gross structural and dynamic
differences from the natural proteins, it is remarkable that the maquettes show
magnetic field effects that are so similar to those observed for cryptochromes.
PMID- 29940117
TI - Photocontrolled Fluorescence "Double-Check" Bioimaging Enabled by a Glycoprobe
Protein Hybrid.
AB - Despite the rapid development of imaging techniques, precise probe localization
and modulation in living cells is still a challenging task. Here we show that the
simple hybridization between a photochromic fluorescent glycoprobe and human
serum albumin (HSA) enables a unique fluorescence "double-check" mechanism for
precisely localizing and manipulating probe molecules in living cells. Docking of
a carbohydrate-modified naphthalimide (Naph)-spiropyran (SP) dyad to a
hydrophobic pocket of HSA produces the glycoprobe-protein hybrid, causing the
protein conformation to fold as determined by small-angle X-ray scattering. We
show that the Naph and merocyanine (the photoisomer of SP) fluorescence of the
resulting hybrid can be reversibly switched by light in buffer solution and in
target cells overexpressing the carbohydrate receptor.
PMID- 29940118
TI - pH-Responsive Biohybrid Carrier Material for Phenol Decontamination in
Wastewater.
AB - Smart polymers are a valuable platform to protect and control the activity of
biological agents over a wide range of conditions, such as low pH, by proper
encapsulation. Such conditions are present in olive oil mill wastewater with
phenol as one of the most problematic constituents. We show that elastic and pH
responsive diblock copolymer fibers are a suitable carrier for Corynebacterium
glutamicum, i.e., bacteria which are known for their ability to degrade phenol.
Free C. glutamicum does not survive low pH conditions and fails to degrade phenol
at low pH conditions. Our tea-bag like biohybrid system, where the pH-responsive
diblock copolymer acts as a protecting outer shell for the embedded bacteria,
allows phenol degradation even at low pH. Utilizing a two-step encapsulation
process, planktonic cells were first encapsulated in poly(vinyl alcohol) to
protect the bacteria against the organic solvents used in the second step
employing coaxial electrospinning.
PMID- 29940119
TI - Isotope Effects Reveal an Alternative Mechanism for "Iminium-Ion" Catalysis.
AB - A novel mechanism for the epoxidation of enals with hydrogen peroxide catalyzed
by diarylprolinol silyl ether supported by experimental 13C kinetic isotope
effects (KIEs) and density functional theory calculations is presented. Normal
13C KIEs, measured on both the carbonyl- and beta-carbon atoms of the enal,
suggest participation of both carbon atoms in the rate-determining step.
Calculations show that the widely accepted iminium-ion mechanism does not account
for this experimental observation. A syn-SN2' substitution mechanism, which
avoids formation of a discrete iminium-ion intermediate, emerges as the most
likely mechanism based on agreement between experimental and predicted KIEs.
PMID- 29940121
TI - Design of Potent pan-IAP and Lys-Covalent XIAP Selective Inhibitors Using a
Thermodynamics Driven Approach.
AB - Recently we reported that rapid determination of enthalpy of binding can be
achieved for a large number of congeneric agents or in combinatorial libraries
fairly efficiently. We show that using a thermodynamic Craig plot can be very
useful in dissecting the enthalpy and entropy contribution of different
substituents on a common scaffold, in order to design potent, selective, or pan
active compounds. In our implementation, the approach identified a critical Lys
residue in the BIR3 domain of XIAP. We report for the first time that it is
possible to target such residue covalently to attain potent and selective agents.
Preliminary cellular studies in various models of leukemia, multiple myeloma, and
pancreatic cancers suggest that the derived agents possess a potentially
intriguing pattern of activity, especially for cell lines that are resistant to
the pan-IAP antagonist and clinical candidate LCL161.
PMID- 29940120
TI - Scaffold-Hopping Approach To Discover Potent, Selective, and Efficacious
Inhibitors of NF-kappaB Inducing Kinase.
AB - NF-kappaB-inducing kinase (NIK) is a protein kinase central to the noncanonical
NF-kappaB pathway downstream from multiple TNF receptor family members, including
BAFF, which has been associated with B cell survival and maturation, dendritic
cell activation, secondary lymphoid organ development, and bone metabolism. We
report herein the discovery of lead chemical series of NIK inhibitors that were
identified through a scaffold-hopping strategy using structure-based design.
Electronic and steric properties of lead compounds were modified to address
glutathione conjugation and amide hydrolysis. These highly potent compounds
exhibited selective inhibition of LTbetaR-dependent p52 translocation and
transcription of NF-kappaB2 related genes. Compound 4f is shown to have a
favorable pharmacokinetic profile across species and to inhibit BAFF-induced B
cell survival in vitro and reduce splenic marginal zone B cells in vivo.
PMID- 29940122
TI - Ultrahigh Numerical Aperture Metalens at Visible Wavelengths.
AB - Subwavelength imaging requires the use of high numerical aperture (NA) lenses
together with immersion liquids in order to achieve the highest possible
resolution. Following exciting recent developments in metasurfaces that have
achieved efficient focusing and novel beam-shaping, the race is on to demonstrate
ultrahigh-NA metalenses. The highest NA that has been demonstrated so far is NA =
1.1, achieved with a TiO2 metalens and back-immersion. Here, we introduce and
demonstrate a metalens with a high NA and high transmission in the visible range,
based on crystalline silicon (c-Si). The higher refractive index of silicon
compared to TiO2 allows us to push the NA further. The design uses the geometric
phase approach also known as the Pancharatnam-Berry (P-B) phase, and we determine
the arrangement of nanobricks using a hybrid optimization algorithm (HOA). We
demonstrate a metalens with NA = 0.98 in air, a bandwidth (full width at half
maximum, fwhm) of 274 nm, and a focusing efficiency of 67% at 532 nm wavelength,
which is close to the transmission performance of a TiO2 metalens. Moreover, and
uniquely so, our metalens can be front-immersed into immersion oil and achieve an
ultrahigh NA of 1.48 experimentally and 1.73 theoretically, thereby demonstrating
the highest NA of any metalens in the visible regime reported to the best of our
knowledge. The fabricating process is fully compatible with microelectronic
technology and therefore scalable. We envision the front-immersion design to be
beneficial for achieving ultrahigh-NA metalenses as well as immersion metalens
doublets, thereby pushing metasurfaces into practical applications such as high
resolution, low-cost confocal microscopy and achromatic lenses.
PMID- 29940123
TI - Origin, Evolution, and Movement of Microlayer in Pool Boiling.
AB - The microlayer thin film is visualized in situ in a vapor bubble during pool
boiling. Contrary to current understanding, bubbles originate on hydrophilic and
silane-coated hydrophobic surfaces without a three-phase contact line, i.e., the
microlayer completely covers the bubble base. The occurrence of such a wetted
bubble base is found to be dependent on the liquid-solid interaction. As the
bubble grows in time, the film decreases in thickness, eventually forming the
contact line and dry region. During this drying out process, curvature at the
center of the microlayer shows a cyclical behavior due to competing Marangoni and
capillary flows, and is characterized as a "dryout viscosity". After the dry
region forms, the mechanism of contact line/microlayer movement of a single
bubble on the hydrophilic surface is experimentally determined, and a generalized
expression of energy required for its unpinning and movement is defined.
PMID- 29940124
TI - Challenging Dogma: The Value of Bolus Fluids in the Early Resuscitation of
Hyperdynamic Sepsis.
PMID- 29940125
TI - Quercetin ameliorates pulmonary fibrosis by inhibiting SphK1/S1P signaling.
AB - Idiopathic pulmonary fibrosis is an agnogenic chronic disorder with high
morbidity and low survival rate. Quercetin is a flavonoid found in a variety of
herbs with anti-fibrosis function. In this study, bleomycin was employed to
induce a pulmonary fibrosis mouse model. The quercetin administration ameliorated
bleomycin-induced pulmonary fibrosis, evidenced by the expression level changes
of hydroxyproline, fibronectin, alpha-smooth muscle actin, Collagen I, and
Collagen III. Similar results were observed in transforming growth factor (TGF)
beta-treated human embryonic lung fibroblast (HELF). The bleomycin or TGF-beta
administration caused the increase of sphingosine-1-phosphate (S1P) level in
pulmonary tissue and HELF cells, as well as its activation-required kinase,
sphingosine kinase 1 (SphK1), and its degradation enzyme, sphinogosine-1
phosphate lyase (S1PL). However, the increase of S1P, SphK1, and S1PL was
attenuated by application of quercetin. In addition, the effect of quercetin on
fibrosis was abolished by the ectopic expression of SphK1. The colocalization of
SphK1/S1PL and fibroblast specific protein 1 (FSP1) suggested the roles of
fibroblasts in pulmonary fibrosis. In summary, we demonstrated that quercetin
ameliorated pulmonary fibrosis in vivo and in vitro by inhibiting SphK1/S1P
signaling.
PMID- 29940127
TI - Recognizing the Unique Role of Critical Care Providers in Confronting
Antimicrobial Resistance.
PMID- 29940126
TI - Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care.
AB - BACKGROUND: In patients with diabetes, hospitalization can complicate the
achievement of recommended glycemic targets. There is increasing evidence that a
closed-loop delivery system (artificial pancreas) can improve glucose control in
patients with type 1 diabetes. We wanted to investigate whether a closed-loop
system could also improve glycemic control in patients with type 2 diabetes who
were receiving noncritical care. METHODS: In this randomized, open-label trial
conducted on general wards in two tertiary hospitals located in the United
Kingdom and Switzerland, we assigned 136 adults with type 2 diabetes who required
subcutaneous insulin therapy to receive either closed-loop insulin delivery (70
patients) or conventional subcutaneous insulin therapy, according to local
clinical practice (66 patients). The primary end point was the percentage of time
that the sensor glucose measurement was within the target range of 100 to 180 mg
per deciliter (5.6 to 10.0 mmol per liter) for up to 15 days or until hospital
discharge. RESULTS: The mean (+/-SD) percentage of time that the sensor glucose
measurement was in the target range was 65.8+/-16.8% in the closed-loop group and
41.5+/-16.9% in the control group, a difference of 24.3+/-2.9 percentage points
(95% confidence interval [CI], 18.6 to 30.0; P<0.001); values above the target
range were found in 23.6+/-16.6% and 49.5+/-22.8% of the patients, respectively,
a difference of 25.9+/-3.4 percentage points (95% CI, 19.2 to 32.7; P<0.001). The
mean glucose level was 154 mg per deciliter (8.5 mmol per liter) in the closed
loop group and 188 mg per deciliter (10.4 mmol per liter) in the control group
(P<0.001). There was no significant between-group difference in the duration of
hypoglycemia (as defined by a sensor glucose measurement of <54 mg per deciliter;
P=0.80) or in the amount of insulin that was delivered (median dose, 44.4 U and
40.2 U, respectively; P=0.50). No episode of severe hypoglycemia or clinically
significant hyperglycemia with ketonemia occurred in either trial group.
CONCLUSIONS: Among inpatients with type 2 diabetes receiving noncritical care,
the use of an automated, closed-loop insulin-delivery system resulted in
significantly better glycemic control than conventional subcutaneous insulin
therapy, without a higher risk of hypoglycemia. (Funded by Diabetes UK and
others; ClinicalTrials.gov number, NCT01774565 .).
PMID- 29940128
TI - A New Technique for Retracting the Protrusive Premaxilla With Fewer Patient
Visits.
AB - Bilateral cleft lip and palate with premaxillary protrusion is a great challenge
due to a large defect area. Retraction of the premaxilla before surgery can be
done with numerous orthopedic treatment options. In patients who have cleft lip
and alveolus, but not cleft palate, it is quite difficult to get to the place
where the premaxilla should be. To effectively reach the location where the
premaxilla should be, new appliances with expansion and retraction screws were
designed. This new design aims to treat the patient with fewer visits. Our study
presents the treatment of a case with excessive premaxillary growth and no
palatal defect treated with our new design.
PMID- 29940129
TI - Cardioprotection by ginseng: experimental and clinical evidence and underlying
mechanisms.
AB - Protection of the ischemic and reperfused myocardium represents a major
therapeutic challenge. Translating results from animal studies to the clinical
setting has been disappointing, yet the need for effective intervention,
particularly to limit heart damage following infarction or surgical procedures
such as coronary artery bypass grafting, is substantial. Among the many compounds
touted as cardioprotective agents is ginseng, a medicinal herb belonging to the
genus Panax, which has been used as a medicinal agent for thousands of years,
particularly in Asian societies. The biological actions of ginseng are very
complex and reflect composition of many bioactive components, although many of
the biological and therapeutic effects of ginseng have been attributed to the
presence of steroid-like saponins termed ginsenosides. Both ginseng and many
ginsenosides have been shown to exert cardioprotective properties in experimental
models. There is also clinical evidence that traditional Chinese medications
containing ginseng exert cardioprotective properties, although such clinical
evidence is less robust primarily owing to the paucity of large-scale clinical
trials. Here, we discuss the experimental and clinical evidence for ginseng,
ginsenosides, and ginseng-containing formulations as cardioprotective agents
against ischemic and reperfusion injury. We further discuss potential mechanisms,
particularly as these relate to antioxidant properties.
PMID- 29940130
TI - MicroRNA-126 attenuates cell apoptosis by targeting TRAF7 in acute myeloid
leukemia cells.
AB - BACKGROUND: Acute myeloid leukemia (AML) has only about 30%-40% five years
survival rate due to the leukemia stem-like cells (LSCs) with self-renewal and
differentiation ability. To address the novel therapeutic targets in LSCs, we
investigated the roles of miRNA-126 and TRAF7 in AML. METHODS: We used qRT-PCR
and western blot to investigate the expression level of miRNA-126 and TRAF7 in
AML cell lines. Then, we uncover the effect of miRNA-126 on AML cell
proliferation and apoptosis by MTT assay and flow cytometric analysis,
separately. Furthermore, dual-luciferase assay and western blot were used to
determine the target of miRNA-126 in AML and potential mechanism of cell
apoptosis suppression of miRNA-126. RESULTS: We found that miRNA-126 was highly
expressed in all AML cell lines and inhibition of miRNA-126 significantly induced
cell death through apoptosis. The suppression of AML apoptosis with high
expression of miRNA-126 was caused by down-regulating TRAF7, which blocked the c
FLIP pathway. CONCLUSION: The role of miRNA-126 in AML makes it a potential
therapeutic target for successful clinical outcome.
PMID- 29940131
TI - Overexpression of RANK and M-CSFR in Monocytes of G551D-Bearing Patients with
Cystic Fibrosis.
PMID- 29940132
TI - The burden of symptomatic skeletal events in castrate-resistant prostate cancer
patients with bone metastases at three Canadian uro-oncology centres.
AB - INTRODUCTION: Metastatic bone disease in castrate-resistant prostate cancer risks
significant morbidity, including symptomatic skeletal events. We estimated the
healthcare resource costs of managing skeletal events. METHODS: A retrospective
chart review was conducted for patients who died from or were treated
palliatively for metastatic castrate-resistant prostate cancer from 2006-2013 at
Centre Hospitalier de l'Universite de Montreal (Montreal), Princess Margaret
Cancer Centre (Toronto), or Vancouver General Hospital (Vancouver). RESULTS: Of
393 patients, 275 (70%) experienced 833 events (85 per 100 patient-years), with a
median (95% confidence interval) time (months) to first event of 17.6 (15.3,
21.7). The mean metastatic bone disease-related healthcare resource use cost
(2014 Canadian dollars) estimate for patients without symptomatic skeletal events
was $9550 and between $22 101 (observed) and $34 615 (adjusted) for patients with
at least one event. Fewer patients in Montreal (55%) experienced events compared
to Toronto (79%) or Vancouver (76%). Median time (months) to first event was
longer in Montreal (25.0 [18.5, 32.6]) than in Toronto (14.6 [9.7, 16.8] or
Vancouver (17.3 [14.8, 24.0]). More patients received bone-targeted therapy in
Montreal (64%) and Toronto (60%) than in Vancouver (24%). Bone-targeted therapy
was mostly administered every 3-4 weeks in Montreal and every 3-4 months in
Toronto. CONCLUSIONS: Metastatic bone disease-related healthcare resource use
costs for Canadian castrate-resistant prostate cancer patients are high.
Symptomatic skeletal events occurred frequently, with the incremental cost of one
or more events estimated between $12 641 and $25 120. Symptomatic skeletal event
incidence and bone-targeted therapy use varied considerably between three
Canadian uro-oncology centres. An important limitation is that only patients who
died from prostate cancer were included, potentially overestimating costs.
PMID- 29940133
TI - Costs variations for percutaneous nephrolithotomy in the U.S. from 2003-2015: A
contemporary analysis of an all-payer discharge database.
AB - INTRODUCTION: We sought to evaluate population-based costs variations and
predictors of outlier costs for percutaneous nephrolithotomy (PCNL) in the U.S.
METHODS: Using the Premier Healthcare Database, we identified all patients
diagnosed with kidney/ureter calculus who underwent PCNL from 2003-2015. We
evaluated 90-day direct hospital costs, defining high- and low-cost surgery as
those >90th and <10th percentile, respectively. We constructed a multilevel,
hierarchical regression model and calculated the pseudo-R2 of each variable,
which translates to the percentage variability contributed by that variable on 90
day direct hospital costs. RESULTS: A total of 114 581 patients underwent PCNL
during the 12-year study period. Mean cost in the low-cost group was $5787 (95%
confidence interval [CI] 5716-5856) vs. $38 590(95% CI 37 357-39 923) in the high
cost group. Cost variations were substantially impacted by patient (63.7%) and
surgical (18.5%) characteristics and less so by hospital characteristics (3.9%).
Significant predictors of high costs included more comorbidities (>=2 vs. 0: odds
ratio [OR] 1.81; p=0.01) and hospital region (Northeast vs. Midwest: OR 2.04;
p=0.03). Predictors of low cost were hospital bed size of 300-499 beds (OR 1.35;
p<0.01) and urban hospitals (OR 2.77; p=0.01). Factors less likely to be
associated with low-cost PCNL were more comorbidities (Charlson Comorbidity Index
[CCI] >=2: OR 0.69; p<0.0001), larger hospitals (OR 0.61; p=0.01), and teaching
hospitals (OR 0.33; p<0.0001). CONCLUSIONS: Our contemporary analysis
demonstrates that patient and surgical characteristics had a significant effect
on costs associated with PCNL. Poor comorbidity status contributed to high costs,
highlighting the importance of patient selection.
PMID- 29940134
TI - External validation of the novel International Society of Urological Pathology
(ISUP) Gleason grading groups in a large contemporary Canadian cohort.
AB - INTRODUCTION: We sought to test the discriminatory ability of the 2014
International Society of Urological Pathology (ISUP) Gleason grading groups (GGG)
for predicting biochemical recurrence (BCR) after robot-assisted radical
prostatectomy (RARP) in a large, contemporary, Canadian cohort. METHODS: A total
of 621 patients who underwent RARP in two major Canadian centres were identified
in a prospectively maintained Canadian database between 2006 and 2016. Followup
endpoint was BCR. Log-rank test, univariable, and multivariable Cox regression
analyses were used. RESULTS: Mean followup was 27.9 months. All five ISUP GGG
independently predicted BCR. Statistically significant differences in BCR rates
were found between GGG 2 and GGG 3 strata (p<0.001). No statistically significant
differences in BCR rates were found between GGG 4 and GGG 5 strata (p=0.3).
Relative to GGG 1, the GGG 2, GGG 3, GGG 4, and GGG 5 yielded a 1.10-, 3.44-,
4.18-, and 4.74-fold hazard ratio (HR) increment in BCR, respectively.
CONCLUSIONS: This population-based Canadian cohort study confirms the added
discriminatory property of the novel ISUP grading, specifically for GGG 2 and GGG
3 strata. No difference, however, was observed between GGG 4 and GGG 5, likely
due to the lower number of patients in these groups. As such, after external
validation, the 2014 ISUP GGG appears to retain clinical prognostic significance
in a Canadian population.
PMID- 29940135
TI - Pediatric cystogram: Are we considering age-adjusted bladder capacity?
AB - INTRODUCTION: There are a small number of reports in the literature describing
bladder rupture during cystograms in children. We hypothesized that children
undergoing cystograms may have their bladder overfilled during the test. We aimed
to evaluate the current practice when performing cystograms in our institution,
contrasting actual volume used to fill the bladder to the age-adjusted bladder
capacity. METHODS: We performed a retrospective review of all voiding
cystourethrograms(VCUG) and radionuclide cystograms (RNC) performed at the
Children's Hospital of Eastern Ontario from 2006-2013. Formulas used to estimate
age-adjusted bladder capacity: 1) infants <1 year: Capacity (mL) = (2.5 * age
[months]) + 38 (Holmdahl et al, 1996); and 2) older children >1 year: Capacity
(mL) = (2 + age [years]) * 30 (Koff et al, 1983). RESULTS: A total of 2411
cystograms were done (1387 VCUG; 1024 RNC) in 817 infants and 1594 children older
than one year - 1113 boys and 1298 girls. Generally, bladders tended to be
overfilled with 32% more volume in mL than the expected age-adjusted bladder
capacity - VCUG 151 (122) mL vs 120 (97) mL (p< 0.001) and RNC 191 (97) mL vs.
151(74) mL (p<0.001). Most importantly, infants had a striking overfilling rate
of 64% and 38 % more volume than their expected age-adjusted bladder capacity for
VCUG and RNC, respectively (p<0.001). CONCLUSION: Bladders are filled above the
estimated age-adjusted capacity in mL at the following rates: 32% in the whole
group and 64% in infants undergoing VCUG. It raises concern of possible bladder
rupture in this age group. Furthermore, this may lead to overgrading and
overdiagnosing of vesicoureteric reflux, as well as overestimation of post-void
residual. Attention should be paid to filling to age-adjusted bladder capacity
and allowing the child adequate time to void during performance of the cystogram.
PMID- 29940136
TI - The association between physician trust and prostate-specific antigen screening:
Implications for shared decision-making.
AB - INTRODUCTION: Shared decision-making is widely recommended when men are
considering prostate cancer screening with prostate-specific antigen (PSA). The
role of patients' trust in cancer information from their physician in such
decisions is unknown. METHODS: We identified male respondents >=18 years of age
from the Health Information National Trends Survey, a population-based survey of
people living in the U.S. (2011-014). We assessed the association between degree
of trust in cancer information from respondent's physician with patient-reported
receipt of PSA-screening and patient-reported discussion of PSA screening with
their physician. RESULTS: Among 5069 eligible respondents, 3606 (71.1%) men
reported trusting cancer information from their physician "a lot," 1186 (23.4%)
"somewhat," 219 (4.3%) "a little," and 58 (1.1%) "not at all." A total of 2655
(52.4%) men reported receiving PSA screening. The degree of trust an individual
had in his physician for cancer information was strongly associated with his
likelihood of having received PSA screening (ptrend<0.0001) (54.9% "a lot" vs.
27.6% "not at all"). These findings persisted after multivariable regression.
Similarly, men who had high levels of trust in their physician were more likely
to have discussed PSA screening with a strong trend across strata
(ptrend<0.0001). CONCLUSIONS: The level of trust an individual has in cancer
information from his physician is strongly associated with his likelihood of
discussing and undergoing PSA screening. As rationale, implementation of PSA
screening requires shared decision-making, and the level of trust an individual
has in his physician has important implications for dissemination of PSA
screening guidelines.
PMID- 29940137
TI - Cost analysis of Greenlight photoselective vaporization of the prostate compared
to transurethral resection of the prostate for benign prostatic hyperplasia.
AB - INTRODUCTION: Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement
of the prostate gland, which results in the development of lower urinary tract
symptoms that can interfere with a patient's daily activities and negatively
impact their quality of life. The gold standard treatment for moderate to severe
BPH has been transurethral resection of the prostate (TURP), however, this
procedure is associated with prolonged hospitalizations and increased
complications. An alternative to TURP is Greenlight photoselective vaporization
of the prostate (PVP), which is associated with better perioperative safety. The
objectives of the research were to 1) assess the cost of Greenlight PVP compared
to TURP and bipolar TURP; and 2) assess the predictors of total cost. METHODS: We
conducted a descriptive costing study from the hospital perspective. We evaluated
perioperative costs of patients who underwent each procedure from 2013-2015 at a
tertiary academic medical centre. A multiple linear regression was performed to
identify predictors of total cost. The variables included in regression analysis
were patient age, type of procedure, Charlson Comorbidity Index, and distance to
clinic. RESULTS: A total of 202 patients received one of the three procedures
over the study period. The total cost of Greenlight PVP was $3836 per patient
compared to $4963 for TURP and $4978 for bipolar TURP. The linear regression
showed that the Charlson Comorbidity Index and type of procedure were independent
predictors of total cost. CONCLUSIONS: The procedure costs and readmission rates
are lower for Greenlight PVP compared to TURP and bipolar TURP, making it a
preferable option for hospitals.
PMID- 29940138
TI - A survey of Canadian renal transplant surgeons: Use of ureteric stents and
technique of the ureteroneocystotomy.
AB - INTRODUCTION: The role of ureteric stenting in renal transplant has been well
demonstrated. The goal of this survey was to determine the utilization of
ureteric stents by Canadian transplant surgeons, and how the ureteroneocystotomy
and followup is performed. METHODS: An online survey was sent to the 40 surgeon
members of the Canadian Society of Transplantation. The primary outcome was the
rate of ureteric stent use at the time of renal transplantation. The secondary
outcomes were the ureteric stent dwell time, use and type of prophylactic
antibiotics, and the use of routine post-transplant ultrasonography. RESULTS: All
respondents (25) used ureteric stent routinely and 92% remove the stent between
four and six weeks postoperatively. Prophylactic antibiotics were used 64% of the
time for ureteric stent removal. The majority of surgeons do not routinely
perform a post-stent removal ultrasound. Fifty-six percent of respondents perform
a refluxing anastomosis. CONCLUSIONS: Ureteric stents are routinely used in renal
transplant in Canada. Areas for improvement and topics of debate identified from
this survey are the need for peri-stent removal antibiotics, the role of post
stent removal ultrasound, the duration of stent dwell time, and the need for a
non-refluxing ureteroneocystotomy.
PMID- 29940139
TI - Multiparametric magnetic resonance imaging - Transrectal ultrasound-guided
cognitive fusion biopsy of the prostate: Clinically significant cancer detection
rates stratified by the Prostate Imaging and Data Reporting System version 2
assessment category.
AB - INTRODUCTION: We aimed to report the clinically significant prostate cancer (PCa)
detection rate in men undergoing magnetic resonance imaging-transrectal
ultrasound (MRI-TRUS)-cognitive fusion (CF) targeted biopsies stratified by the
Prostate Imaging and Data Reporting System (PI-RADS) version 2 (v2) scores.
METHODS: With a quality assurance waiver from the IRB, we identified a cohort of
men who underwent MRI-TRUS-CF and synchronous template biopsy from 2015-2017. MRI
(PI-RADS v2 score, lesion size, lesion location [peripheral or transition zone
(PZ/TZ)]), and CF-TRUS biopsy (operator experience, TRUS visibility, and number
of biopsies) features were extracted. The primary outcome was diagnosis of
clinically significant (Gleason score >=3+4=7 or International Society of
Urological Pathology (ISUP) grade group >=2) PCa. RESULTS: During the study
period, 131 men (with 142 PIRADS v2 score >=3 lesions) met inclusion criteria; 98
men had previously negative template biopsy and 33 were on active surveillance
for previously detected low-grade PCa. In total, 41.9% (55/131) men had
clinically significant PCa - 17.6% (23/131) detected on targeted biopsy only,
8.4% (11/131) on template biopsy only, and 16.0% (21/131) on both targeted and
template biopsy. Clinically significant PCa detection stratified by PI-RADS v2
scores were: 11.1% (3/27) for score 3 (indeterminate), 42.9% (24/56) for score 4
(significant cancer likely), and 35.6% (21/59) for score 5 (significant cancer
very likely). Clinically significant PCa detection rates in targeted biopsies
were better among PZ (41.8% [33/79]) compared to TZ (23.8% [15/63]) lesions
(p=0.025) in TRUS visible lesions (p=0.033) and in the most experienced
radiologists (p=0.05), with no difference by lesion size or number of additional
core biopsies performed (all p>0.05). CONCLUSIONS: Cognitive fusion MRI-TRUS
guided targeted biopsy yielded substantially lower rates of clinically
significant cancer in PI-RADS v2 score 4 and 5 lesions when compared to published
results using in-bore MR-guided or automated MRI-TRUS fusion guidance systems.
Cancer detection was worst for TZ lesions.
PMID- 29940140
TI - Modified parallel strategies for preparation of heteroduplex plasmids for in
vitro mismatch repair assays.
AB - We present efficient and reproducible parallel strategies for preparing large
quantities of pure heteroduplex plasmids containing defined mismatches. The
strategies described involve the use of synthetic oligonucleotides, the
commercially available pGEM-T plasmid, and nicking enzymes to prepare
prerequisite ssDNA. Alternatively, bacterial packaging cell lines containing an
engineered phagemid construct to produce ssDNA without the need of a helper phage
were utilized, hence providing added flexibility and choice. These integrated
approaches help to construct different mismatch substrates of choice in large
quantities, thus enhancing the usability of mismatch repair assays and extending
their range and accessibility to wider research groups.
PMID- 29940141
TI - Evaluation of the CKD-EPI creatinine based glomerular filtration rate estimating
equation in Black African and Indian adults in KwaZulu-Natal, South Africa.
AB - BACKGROUND: The estimation of glomerular filtration rate (GFR) plays a vital role
in assessment of the renal function. This study evaluated the performance of the
CKD-EPIcreat and MDRD equations in the South African Kwa-Zulu Natal population.
OBJECTIVES: The objectives if the study were to compare the of CKD-EPIcreat and
MDRD equations in the selected population to the measured GFR using Sodium
Technetium-99 m-diethylene-triamine-pentaacetate clearance derived GFR. METHOD:
Records of adult patients with measured GFR performed at the Nuclear Medicine
Department at Inkosi Albert Luthuli Central Hospital, Durban, South Africa from 1
April 2014 to 31 March 2016 were reviewed. eGFR for all included patients was
calculated using the MDRD equation without African American correction factor and
the CKD-EPIcreat equation with and without the African American correction factor
for the Black African patients. Statistical comparison of the eGFR with measured
GFR was performed with Bland Altman bias plots, Wilcoxon match pairs signed ranks
test and accuracy within 10% and 30%.ROC curve analysis assessed the sensitivity
and specificity at eGFR <90 and < 60 ml/min/1.73m2. RESULTS: After exclusion, 287
patients were included for analysis with sufficient numbers for only the Black
African and Indian patients. None of the equations showed accuracy of eGFR within
30% of measured GFR for 90% of patients. In the Black African population, the CKD
EPIcreat equation without the correction factor performed best. 17% and 14.4% of
the Black African participants would be reclassified with the CKD-EPIcreat
equation without and with the African American correction factor respectively
compared to mGFR at a cut-off of 60 mls/min/1.73m2. CONCLUSION: None of the
evaluated equations attained the 2002 KDOQI benchmark of P30 >90%. 11.1-17% of
individuals would have been incorrectly classified using the CKD-EPIcreat
equation.
PMID- 29940142
TI - The developmental origin of heart size and shape differences in Astyanax
mexicanus populations.
AB - Regulation of heart size and shape is one of the least understood processes in
developmental biology. We have for the first time analysed the hearts of Astyanax
mexicanus and identified several differences in heart morphology between the
surface (epigean morph) and cave-dwelling (troglomorph) morphs. Examination of
the adult revealed that the troglomorph possesses a smaller heart with a rounder
ventricle in comparison to the epigean morph. The size differences identified
appear to arise early in development, as early as 24 h post-fertilisation (hpf),
while shape differences begin to appear at 2 days post-fertilisation. The heart
of the first-generation cross between the cave-dwelling and river-dwelling morph
shows uncoupling of different phenotypes observed in the parental populations and
indicates that the cardiac differences have become embedded in the genome during
evolution. The differences in heart morphology are accompanied by functional
changes between the two morphs, with the cave-dwelling morph exhibiting a slower
heart rate than the river-dwelling morph. The identification of morphological and
functional differences in the A. mexicanus heart could allow us to gain more
insight into how such parameters are regulated during cardiac development, with
potential relevance to cardiac pathologies in humans.
PMID- 29940143
TI - The inhibition of RANKL expression in fibroblasts attenuate CoCr particles
induced aseptic prosthesis loosening via the MyD88-independent TLR signaling
pathway.
AB - Periprosthetic osteolysis and aseptic loosening are mainly caused by wear
particles (Ps) that are generated from friction interfaces. However, the
mechanisms underlying the development of aseptic loosening remain unclear.
Therefore, we aimed toclarify how the myeloid differentiation factor 88 (MyD88)
independent Toll-like receptor (TLR) signaling pathway mediates cobalt and
chromium (CoCr)-Ps-induced osteolysis. We quantified the expression levels of
TLRs, MyD88, RANKL, and inflammatory factors in patients experiencing aseptic
loosening after primary total hip arthroplasty (THA) with metal-on-metal (MoM)
bearings and hip osteoarthritis (hOA). We observed the in vitro and in vivo
levels of RANKL, TLRs, and MyD88 in fibroblasts challenged with CoCr Ps by
applying shMyD88 interference lentivirus vectors to block the MyD88-independent
TLR pathway. The levels of TLRs, MyD88, RANKL, and inflammatory factors in the
revision THA (rTHA) with MoM group were higher than those in the hOA group. Our
data collectively revealed that inhibiting MyD88 expression could reduce
osteoclastogenesis in vitro and CoCr-Ps-induced osteolysis in vivo. Our findings
suggested that osteoclastogenesis is promoted by the CoCr-Ps-induced expression
of RANKL in fibroblasts and that MyD88 is a potential target in the treatment of
wear Ps-induced osteolysis.
PMID- 29940144
TI - Kruppel-like factor 4 expression in solid tumor prognosis: A meta-analysis.
AB - BACKGROUND: Accumulating studies have demonstrated that Kruppel-like factor 4
(KLF4) can act as a tumor suppressor or oncogene in the carcinogenesis of diverse
cancers. The prognostic value of KLF4 in various human solid cancers remains
controversial. Thus, the present meta-analysis was conducted to evaluate the
prognostic value of KLF4 in solid tumors. METHODS: Eligible literature was
retrieved by searching the PubMed, Embase, and Cochrane Library. Combined hazard
ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were
assessed using fixed-effects and random-effects models. Meta-regression and
subgroup analyses were performed to identify the source of heterogeneity. In
addition, publication bias was assessed using Begg's funnel plot and Egger's
regression asymmetry test. RESULTS: The 22 eligible studies finally enrolled a
total of 2988 patients to assess the prognostic value of KLF4 in solid tumors.
Low KLF4 expression was clearly related to worse OS (HR = 1.71, 95% confidence
interval [CI] = 1.30-2.24, P < 0.001) and DFS (HR = 1.74, 95% CI = 1.34-2.26, P <
0.001), indicating that low KLF4 expression could be an independent prognostic
factor for poor survival in solid cancers. CONCLUSION: KLF4 might be a potential
marker to predict prognosis in solid cancer patients.
PMID- 29940145
TI - Improvement of sensitive and specific detection of circulating tumor cells using
negative enrichment and immunostaining-FISH.
AB - BACKGROUND: Circulating tumor cells (CTCs) provide an opportunity to obtain
pivotal biological information required for the development of personalized
medicine. However, the current assays of CTCs' detection face serious challenges
regarding specificity and sensitivity. METHODS: In this study, we developed a
novel strategy that combined negative enrichment (NE), immunocytochemistry CD45
staining and fluorescence in situ hybridization (FISH) to identify, enumerate and
characterize CTCs. CTCs were identified as DAPI+/CD45-/Chromosome multiploid. The
assay was evaluated with different cancer cell lines including lung, breast,
esophageal and gastric cancer. And then, the developed assay was applied in
cancer patients to explore the possibility of clinical application and whether
CTC number was related to clinicopathological factors. RESULTS: The average
recover rate of esophageal cancer cell line Eca-109 using negative enrichment was
higher than 80% and the multiploid cells rate of four cancer cell lines were
>96%, which demonstrate the NE-FISH platform is favorable for CTCs detection.
CTCs count was significantly higher in lung cancer patients than healthy controls
and benign lung disease with an area under ROC curve of 0.905 (95% confidence
interval 0.866-0.944, P < .001). Using a cutoff value of 2 CTCs, the positive
rate of detecting lung, gastric, breast and esophageal cancer patients were
71.33%, 86.21%, 76.77% and 78.35%, respectively. Besides, CTCs could be detected
in stage I with the positive rate of 64.15% for lung cancer, 83.33% for gastric
cancer, 78.95% for breast cancer and 68.18% for esophageal cancer, which may
promote the early diagnose and influence the treatment decision for better
management of those cancer in clinic. CONCLUSIONS: Our study showed that CTCs
could be detected in diverse cancers using the novel NE-FISH platform with high
sensitivity and specificity. Therefore, analysis of CTCs with NE-FISH has a clear
potential to improve the management of cancer patients in clinical use.
PMID- 29940146
TI - Urinary Syndecan-1 and acute kidney injury after pediatric cardiac surgery.
AB - INTRODUCTION: Acute kidney injury (AKI) is a common occurrence after pediatric
cardiac surgery. Plasma syndecan-1 is a biomarker of endothelial glycocalyx
damage and it is associated with AKI. Syndecan-1 is also expressed in renal
tubular cells but there is no study evaluating urinary syndecan-1 in predicting
AKI. METHODS: Prospective cohort study with 86 patients <=18 years submitted to
cardiac surgery at one reference institution. Postoperative urinary syndecan-1
was collected within the first 2 h after cardiac surgery. Severe AKI - defined
according to KDIGO as stage 2 or 3 - doubling of serum creatinine from the
preoperative value or need for dialysis during hospitalization was the main
outcome. Analyses were adjusted for clinical cofounders. RESULTS: Postoperative
urinary syndecan-1 levels were higher in patients with severe AKI and even after
adjustment for several clinical variables; the fourth quartile was significantly
associated with severe AKI. The AUC-ROC for postoperative urinary syndecan-1
showed good discriminatory capacity (AUC-ROC = 0.793). The addition of urinary
syndecan-1 improved the discrimination capacity of a clinical model (0.78 to
0.84). It also improved risk prediction, as measured by net reclassification
improvement (NRI). CONCLUSION: Urinary syndecan-1 predicts severe AKI after
pediatric cardiac surgery. Moreover, it appears to add capacity to predict severe
AKI into a clinical model.
PMID- 29940147
TI - Lipophilic antioxidants in neurodegenerative diseases.
AB - Oxidative stress is commonly involved in the pathogenesis of various
neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease,
Huntington's disease and amyotrophic lateral sclerosis. Therefore, lipophilic
antioxidants, such as vitamin A, carotinoids, vitamin E, coenzyme Q10,
docosahexaenoic acid and eicosapentaenoic acid, have received increasing
attention as therapeutic and preventive intervention for neurodegenerative
diseases. Although difficulties exist with clinical studies due to the nature of
the long-standing progression of neurodegenerative diseases, findings in cell and
animal models, as well as biomarker studies have implied a relationship between
lipophilic antioxidants and neurodegeneration. By reviewing current findings and
their implication in neurodegenerative diseases, we conclude that although none
of these lipophilic antioxidants have yet provided clear-cut clinical evidence
toward beneficial effects in neurodegenerative diseases, they could demonstrate
neuroprotection in cellular and/or animal studies. Results from future
multidisciplinary studies with optimization of factors including drug dosage,
delivery route and chemical structure may provide us with novel treatments for
neurodegenerative diseases using lipophilic antioxidants.
PMID- 29940148
TI - Effects of liver-targeted drugs on expression of immune-related proteins in
hepatocellular carcinoma cells.
AB - BACKGROUND: The molecular mechanisms involved in the development and metastasis
of hepatocellular carcinoma (HCC) are complex. Molecule-targeted drugs are
characterized by strong specificity and low toxicity, but the clinical research
of these drugs still exhibits many difficulties, such as poor target specificity.
With the in-depth study of the tumor immunological theory, therapies based on
overcoming the tumor immune escape to produce a specific effective tumor immune
response has gradually become a hot topic in tumor research. We hope that by
studying the effects of liver-targeted drugs on the expression of immune-related
proteins in hepatocellular carcinoma cells, we will find a potential link to
further guide the clinical drug use. METHODS: Human hepatoma Hep3B cells were
used to establish liver cancer xenografts by inoculating 40 BALB/c nude mice. The
following five groups of mice (8 mice per group) were randomly set up: lenvatinib
group, apatinib group, sorafenib group, regorafenib group, and dimethyl sulfoxide
(DMSO) group. After treatment, we analyzed PD-L1 and B7-H3 mRNA using the real
time polymerase chain reaction (PCR) assay and assessed the PD-L1 and B7-H3
protein expression by Western immunoblotting. RESULTS: Real-time PCR results
suggested that the mRNA expression of PD-L1 in the lenvatinib group was
significantly higher than that in the control group, while its expression in the
regorafenib group was significantly lower than that in the control group (both p
< .05). Western immunoblotting results suggested that, compared with the control
group, PD-L1 protein was increased in the lenvatinib group, while its expression
in the regorafenib group was decreased. CONCLUSION: Lenvatinib and regorafenib
affected the expression of PD-L1 in the process of anti-HCC.
PMID- 29940149
TI - Structure, Process, and Outcome Data of AWHONN's Postpartum Hemorrhage Quality
Improvement Project.
AB - OBJECTIVE: To describe the structures and processes implemented during the
Association of Women's Health, Obstetric, and Neonatal Nurses Postpartum
Hemorrhage (AWHONN PPH) Project. DESIGN: An 18-month, multiregion, multihospital
quality improvement project. SETTING/LOCAL PROBLEM: Fifty-eight hospitals located
in Washington, DC; Georgia; and New Jersey. PARTICIPANTS: Volunteer registered
nurse hospital leaders implemented the AWHONN PPH bundle, which consisted of
structure and process improvements. INTERVENTION/MEASUREMENTS: The process and
effectiveness of the implementation of the interventions were measured and
compared between baseline and after implementation. RESULTS: All structures and
processes showed improvement but were not fully implemented at all sites.
Registered nurse participation in drills increased from 0% to 92%, quantification
of blood loss increased from 5% to 45%, hemorrhage risk assessment increased from
10% to 70%, prebirth risk assessment increased from 2% to 52%, postbirth risk
assessment increased from 2% to 57%, and debriefing increased from 1% to 13%. No
statistically significant differences were found in the pre- and
postimplementation outcomes measured (maternal deaths, blood products transfused,
women with massive transfusions, peripartum hysterectomies during the birth
admission, and ICU admissions for women who gave birth and/or had a postpartum
hemorrhage). Participants' self-assessments of their monthly implementation
efforts (leader intensity) were not correlated with implementation fidelity (the
degree to which the intervention was provided as proposed). CONCLUSION: None of
the 58 hospitals were able to implement all of the structure and process changes
before the end of the 18-month implementation phase. This suggests that an 18
month implementation phase may be too short.
PMID- 29940150
TI - Altruism: A Story in Three Acts.
PMID- 29940151
TI - Individual and Joint Effects of Pulse Pressure and Blood Pressure Treatment
Intensity on Serious Adverse Events in the SPRINT Trial.
AB - PURPOSE: The objective of this study was to determine individual and joint
effects of pulse pressure and blood pressure treatment intensity on serious
adverse events in the Systolic Blood Pressure Intervention Trial. METHODS: Pulse
pressure was calculated by subtracting diastolic blood pressure from systolic
blood pressure. Blood pressure treatment intensity goal was <=140mm Hg in the
control arm and <=120mm Hg in the intensive arm. The primary outcome was a 5
point composite of hypotension, syncope, electrolyte abnormalities, acute renal
insufficiency, or injurious falls. RESULTS: In 9361 trial participants, the
incident rate for the primary outcome per 1000 person-years increased with higher
pulse pressure category: <=49 mmHg: 20.4 (17.2-24.1), 50-59 mmHg: 24.5 (21.3
28.2), 60-69 mmHg: 31.7 (27.7-36.2), >=70 mmHg: 44.6 (39.8-49.9; Ptrend < .0001;
hazard ratio [HR] of pulse pressure [every 10mm Hg] 1.23; 95% confidence interval
[CI], 1.18-1.28). The intensive treatment arm had a higher incidence rate of
serious adverse events than the control arm (34.2, 95% CI, 31.2-37.3, vs 26.0,
95% CI, 23.4-28.8, P = .0001; HR 1.32; 95% CI, 1.15-1.51). The combined effect
was not significant in the relative risk scale (HR 0.97, Pinteraction = .48) but
was significant in the risk difference scale (P = .027), contributing 2.5
additional serious adverse events per 1000 person-years for every 10mm Hg
increase in pulse pressure in excess of the individual effects of pulse pressure
and treatment intensity. CONCLUSIONS: Wider pulse pressure and intensive blood
pressure treatment were individually associated with the composite adverse event
outcome. A modest effect modification of pulse pressure and treatment intensity
led to additional adverse events when both were present. Clinicians should use
caution when treating older patients with elevated pulse pressure to an intensive
blood pressure treatment target.
PMID- 29940152
TI - Crystal structure of the flavin reductase of Acinetobacter baumannii p
hydroxyphenylacetate 3-hydroxylase (HPAH) and identification of amino acid
residues underlying its regulation by aromatic ligands.
AB - The first step in the degradation of p-hydroxyphenylacetic acid (HPA) is
catalyzed by the two-component enzyme p-hydroxyphenylacetate 3-hydroxylase
(HPAH). The two components of Acinetobacter baumannii HPAH are known as C1 and
C2, respectively. C1 is a flavin reductase that uses NADH to generate reduced
flavin mononucleotide (FMNH-), which is used by C2 in the hydroxylation of HPA.
Interestingly, although HPA is not directly involved in the reaction catalyzed by
C1, the presence of HPA dramatically increases the FMN reduction rate. Amino acid
sequence analysis revealed that C1 contains two domains: an N-terminal flavin
reductase domain, and a C-terminal MarR domain. Although MarR proteins typically
function as transcription regulators, the MarR domain of C1 was found to play an
auto-inhibitory role. Here, we report a crystal structure of C1 and small-angle X
ray scattering (SAXS) studies that revealed that C1 undergoes a substantial
conformational change in the presence of HPA, concomitant with the increase in
the rate of flavin reduction. Amino acid residues that are important for HPA
binding and regulation of C1 activity were identified by site-directed
mutagenesis. Amino acid sequence similarity analysis revealed several as yet
uncharacterized flavin reductases with N- or C-terminal fusions.
PMID- 29940153
TI - Role of mitochondrial outer membrane in the uncoupling activity of N-terminally
glutamate-substituted gramicidin A.
AB - Of a series of gramicidin A (gA) derivatives, we have earlier found the peptide
[Glu1]gA exhibiting very low toxicity toward mammalian cells, although
dissipating mitochondrial membrane potential with almost the same efficiency as
gA. Substitution of glutamate for valine at position 1 of the gA amino acid
sequence, which is supposed to interfere with the formation of ion-conducting gA
channels via head-to-head dimerization, reduces both channel-forming potency of
the peptide in planar lipid bilayer membranes and its photonophoric activity in
unilamellar liposomes. Here, we compared [Glu1]gA and gA abilities to cause
depolarization of the inner mitochondrial membrane in mitochondria and
mitoplasts, the latter lacking the outer mitochondrial membrane. Importantly,
much less gA was needed to decrease the membrane potential in mitoplasts than in
mitochondria, whereas the depolarizing potency of [Glu1]gA was nearly the same in
these systems. Moreover, in multilamellar liposomes, [Glu1]gA exhibited more
pronounced protonophoric activity than gA, in contrast to the data for
unilamellar liposomes. These results allowed us to conclude that [Glu1]gA has a
much higher permeability between adjacent lipid membranes than gA. Therefore, the
fraction of peptide molecules, reaching the inner mitochondrial membrane upon the
addition to cells, is much higher for [Glu1]gA compared to gA. Under these
conditions, the decreased cytotoxicity of [Glu1]gA could be associated with its
low efficiency as a channel-former dissipating potassium and sodium ion gradients
across plasma membrane. The present study highlighted the role of the ability to
permeate among various biological membranes for intracellular efficiency of
ionophores.
PMID- 29940154
TI - Methyl ferulic acid attenuates ethanol-induced hepatic steatosis by regulating
AMPK and FoxO1 Pathways in Rats and L-02 cells.
AB - Methyl ferulic acid (MFA) is a biologically active monomer extracted and purified
from the Chinese herbal medicine Securidaca inappendiculata hasskarl. The
previously studies showed that MFA improved acute liver injury induced by
ethanol. However, the effect of MFA on ethanol-induced hepatic steatosis in
alcoholic liver disease (ALD) still remains unclear. The current study was aimed
at elucidating the effect of MFA on alcohol-induced hepatic steatosis and the
underlying mechanisms. Human hepatocyte L-02 cells exposed to 200 mM ethanol for
24 h to simulate alcoholic steatosis in vitro. SD rats were fed a Lieber-DeCarli
diet containing 5% (w/v) alcohol for 16 weeks to induce alcoholic liver disease
in vivo. We examined the effect of MFA on ethanol-induced lipid deposition in L
02 cells and SD rats. The results showed that MFA reduced the accumulation of
lipid in L-02 cells, improved alcoholic liver injury in rats, alleviated hepatic
pathological lesions, and reduced lipid deposition in rat serum and liver.
Further studies suggest that MFA reduces lipid synthesis by activating AMPK
ACC/MAPK-FoxO1 pathway. In addition, MFA also promotes lipid oxidation by up
regulating the expression of SIRT1, PPAR-alpha, and CPT-1alpha. Taken together,
MFA ameliorates ethanol-induced hepatic steatosis by activating AMPK-ACC/MAPK
FoxO1 pathway and up-regulating the expression levels of SIRT1, PPAR-alpha, and
CPT-1alpha.
PMID- 29940155
TI - A cell-based assay for the detection of pathogenic anti-voltage-gated calcium
channel autoantibodies in immunoglobulin G from patients with type 1 diabetes.
AB - Recent studies have postulated the presence of functional autoantibodies (Abs)
against L-type voltage gated calcium channels (VGCCs) in the serum of patients
with type 1 diabetes, with various proposed physiological consequences, both
islet cell associated and extra-glandular. Arguably, the most potentially
damaging effect reported for these Abs is induction of apoptosis in pancreatic
beta (beta) cells, yet a convincing pathogenic mechanism remains to be
demonstrated. In the current study, we report an assay of reactive oxygen species
(ROS) stress induction in the rat insulinoma cell line Rin A12, as determined by
2', 7'-Dichlorofluorescein diacetate (DCF-DA) fluorescence detection by flow
cytometry. We demonstrate that incubation of Rin A12 cells with immunoglobulin G
(IgG) containing anti-VGCC activity from patients with T1D mediates a significant
increase in ROS, with subsequent induction of apoptosis, as determined by
positivity for annexin V expression. Neither T1D patient-derived IgG lacking anti
VGCC activity or IgG from healthy donors altered ROS or annexin V expression,
indicating the new assay is specific for the detection of functional anti-VGCC
Abs. Subsequent screening of IgG samples derived from individual patients
indicated a prevalence of approximately 75% in a cohort of 20 patients with T1D.
The new cell-based assay provides, for the first time, experimental evidence
supporting a plausible pathophysiological mechanism underlying anti-VGCC Ab
mediated apoptosis induction in beta cells. Additionally, the assay is a
considerable advance on previously published methods for detecting and
characterising the functional activity of anti-VGCC Abs in patient-derived
samples.
PMID- 29940157
TI - Correlation between PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients.
AB - BACKGROUND: Data about correlation of interleukins (IL-1 alpha, IL-1 beta, IFN
gamma, IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin,
monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator
inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFalpha), ferritin, C reactive
protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis
model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim
of this study was to evaluate the possible correlations of serum levels of PAI-1,
leptin and ferritin with HOMA in HIV/AIDS patients treated with combined
antiretroviral therapy (cART). METHODS: This cross-sectional study included 64
HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre,
Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using
the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while
adiponectin and resistin levels were measured using Metabolic Syndrome Array II
(Randox Laboratories Ltd., London, UK), interleukins (IL-1 alpha, IL-1 beta, IFN
gamma, IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-alpha as well as VEGF was
measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin
resistance was determined using the homeostasis model assessment index (HOMA).
Multicollinearity of independent variables in multivariate model was analyzed
using Variance Inflation Factor. RESULTS: Correlation analysis revealed
significant correlations between HOMA and waist circumference, body mass index,
patients' age, number of cART combinations and triglycerides (p = 0.001, p =
0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated
with levels of high density lipoprotein (HDL) (Rho = -0.282; p = 0.025). PAI-1
(Rho = 0.334; p= 0.007) and leptin (Rho = 0.492; p = 0.001) together with
ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with
HOMA. Levels of IL-1 alpha, IL-1 beta, IFN gamma, IL-2, IL-4, IL-6, IL-8, IL-10,
adiponectin, MCP-1, resistin, TNF-alpha, CRP and VEGF did not significantly
correlate with HOMA. Further, multiple logistic regression showed that there is a
statistically significant correlation between PAI, leptin and ferritin with HOMA
levels (p = 0.042; p < 0.001, p = 0.009). CONCLUSIONS: We showed significant
correlation between PAI-1, leptin and ferritin, independently of each other with
HOMA, in HIV/AIDS patients on cART.
PMID- 29940158
TI - The inhibitory effect of NUCB2/nesfatin-1 on appetite regulation of Siberian
sturgeon (Acipenser baerii Brandt).
AB - Since NUCB2 was discovered, the information about NUCB2/nesfatin-1 in appetite
regulation in both mammals and teleost has been still limited. The present study
aims to determine the effects of nesfatin-1 on food intake and to explore the
appetite mechanism in Siberian sturgeon. In this study, nucb2 cDNA sequence of
1571 bp was obtained, and the mRNA expression of nucb2 was abundant in brain and
liver. Levels of nucb2 were appreciably increased in brain after feeding 1 and 3
h, while significantly decreased within fasting 15 days. Except for fasting 1
day, the expression pattern of nucb2 in the liver was similar to the brain. Acute
intraperitoneal (i.p.) injection of nesfatin-1 inhibited the food intake during 0
1 h in a dose-dependent manner and 50 or 100 ng/g BW nesfatin-1 significantly
decreased the cumulative food intake during 3 h. The daily food intake and
cumulative food intake were remarkably reduced post chronic (7 days) i.p.
injection. Moreover, chronic i.p. injection of nesfatin-1 affected the expression
of appetite factors including cart, apelin and pyy in the brain, stomach and
liver with the consistent pattern of change, while the levels of cck, ucn3 and
nucb2 in these have different patterns. This study demonstrates that nesfatin-1
acts as a satiety factor in reducing the short-term and long-term food intake of
Siberian sturgeon. Therefore, the data suggesting nesfatin-1 inhibits the
appetite through different signal pathways in the central and peripheral
endocrine systems of Siberian sturgeon.
PMID- 29940159
TI - RhoA regulates Schwann cell differentiation through JNK pathway.
AB - RhoA is a small GTPase that regulates many functions of mammalian cells via actin
reorganization. Lots of studies uncovered that its activation acts as a major
negative regulator of neurite extension, and inhibition of RhoA activity or
reduction of its expression can promote neuron survival and axonal regeneration.
However, little is known about whether RhoA also exerts important functions on
Schwann cells (SCs) which are the glial cells of the peripheral nervous system
(PNS). Recently, we reported that RhoA plays important roles in the
proliferation, migration and myelination of SCs. In the present study, using RNA
interference to knockdown RhoA expression and CT04 (a cell-permeable C3
Transferase) to inhibit RhoA activation we found that blocking RhoA can slack SC
differentiation. Unexpectedly, inhibiting ROCK, the mostly well-known downstream
effector of RhoA, has no influence on SC differentiation. Instead, the inhibition
of RhoA in differentiating SCs results in the activation of JNK and p38 MAPK. And
the inhibitor of JNK but not p38 MAPK can promote SC differentiation in the
presence of RhoA inhibition. Overall results indicate that RhoA plays a vital
role in SC differentiation via JNK pathway rather than ROCK pathway.
PMID- 29940156
TI - Substrates and potential therapeutics of ventricular arrhythmias in heart
failure.
AB - Heart failure (HF) is a clinical syndrome characterized by ventricular
contractile dysfunction. About 50% of death in patients with HF are due to fetal
ventricular arrhythmias including ventricular tachycardia and ventricular
fibrillation. Understanding ventricular arrhythmic substrates and discovering
effective antiarrhythmic interventions are extremely important for improving the
prognosis of patients with HF and reducing its mortality. In this review, we
discussed ventricular arrhythmic substrates and current clinical therapeutics for
ventricular arrhythmias in HF. Base on the fact that classic antiarrhythmic drugs
have the limited efficacy, side effects, and proarrhythmic potentials, we also
updated some therapeutic strategies for the development of potential new
antiarrhythmic interventions for patients with HF.
PMID- 29940160
TI - Myelinated axons fail to develop properly in a genetically authentic mouse model
of Charcot-Marie-Tooth disease type 2E.
AB - We have analyzed a mouse model of Charcot-Marie-Tooth disease 2E (CMT2E)
harboring a heterozygous p.Asn98Ser (p.N98S) Nefl mutation, whose human
counterpart results in a severe, early-onset neuropathy. Behavioral,
electrophysiological, and pathological analyses were done on separate cohorts of
NeflN98S/+ mutant mice and their wild type Nefl+/+ littermates between 8 and 48
weeks of age. The motor performance of NeflN98S/+ mice, as evidenced by altered
balance and gait measures, was impaired at every age examined (from 6 to 25 weeks
of age). At all times examined, myelinated axons were smaller and contained
markedly fewer neurofilaments in NeflN98S/+ mice, in all examined aspects of the
PNS, from the nerve roots to the distal ends of the sciatic and caudal nerves.
Similarly, the myelinated axons in the various tracts of the spinal cord and in
the optic nerves were smaller and contained fewer neurofilaments in mutant mice.
The myelinated axons in both the PNS and the CNS of mutant mice had relatively
thicker myelin sheaths. The amplitude and the nerve conduction velocity of the
caudal nerves were reduced in proportion with the diminished sizes of myelinated
axons. Conspicuous aggregations of neurofilaments were only seen in primary
sensory and motor neurons, and were largely confined to the cell bodies and
proximal axons. There was evidence of axonal degeneration and regeneration of
myelinated axons, mostly in distal nerves. In summary, the p.N98S mutation causes
a profound reduction of neurofilaments in the myelinated axons of the PNS and
CNS, resulting in substantially reduced axonal diameters, particularly of large
myelinated axons, and distal axon loss in the PNS.
PMID- 29940161
TI - The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers
for Alzheimer's disease diagnosis: A review.
AB - INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers have the potential to improve
the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized
preanalytical CSF handling protocols. METHODS: This systematic review summarizes
the current literature on the influence of preanalytical variables on CSF
biomarker concentration. We evaluated the evidence for three core CSF biomarkers:
beta-amyloid 42, total tau, and phosphorylated tau. RESULTS: The clinically
important variables with the largest amount of conflicting data included the
temperature at which samples are stored, the time nonfrozen samples can be
stored, and possible effects of additives such as detergents, blood
contamination, and centrifugation. Conversely, we discovered that there is
consensus that tube material has a significant effect. DISCUSSION: A unified CSF
handling protocol is recommended to reduce preanalytical variability and
facilitate comparison of CSF biomarkers across studies and laboratories. In
future, experiments should use a gold standard with fresh CSF collected in low
binding tubes.
PMID- 29940162
TI - Biomarkers of agitation and aggression in Alzheimer's disease: A systematic
review.
AB - INTRODUCTION: Agitation is one of the most challenging neuropsychiatric symptoms
to treat in Alzheimer's disease and has significant implications for patient and
caregiver. A major source of difficulty in identifying safe and effective
treatments for agitation is the lack of validated biomarkers. As such, patients
may not be appropriately targeted, and biological response to pharmacotherapy
cannot be adequately monitored. METHODS: This systematic review aimed to
summarize evidence on the association between biomarkers and agitation/aggression
in patients with Alzheimer's disease, utilizing the National Institute on Aging
Alzheimer's Association Research Framework and the Biomarkers, EndpointS, and
other Tools Resource of the Food and Drug Association-National Institutes of
Health Biomarker Working Group. RESULTS: This review identified six classes of
biomarkers (neuropathological, neurotransmitter, neuroimaging, apolipoprotein E
(APOE) genotype, inflammatory, and clusterin) associated with
agitation/aggression, which were mostly diagnostic in nature. DISCUSSION: Future
studies should investigate the predictive, prognostic, and monitoring capacity of
biomarkers to provide insight into the longitudinal course of
agitation/aggression, as well as predict and monitor biological response to a
pharmacological intervention.
PMID- 29940163
TI - Clinical and Hemodynamic Correlates of Pulmonary Arterial Stiffness in Incident,
Untreated Patients With Idiopathic Pulmonary Arterial Hypertension.
AB - BACKGROUND: The role of decreased pulmonary arterial (PA) compliance (C),
equivalent to increased PA stiffness (1/C), as a critical determinant of right
ventricular dysfunction and prognosis has been emphasized in pulmonary arterial
hypertension (PAH). METHODS: This study retrospectively reviewed all incident
patients diagnosed with idiopathic PAH according to right heart catheterization
who were enrolled in the French Pulmonary Arterial Hypertension Network registry
between 2006 and 2016 and who had complete baseline data allowing calculation of
stiffness (PA pulse pressure/stroke volume index). RESULTS: In the 719 patients
included (median age: 66 years; 53.7% female), PA stiffness was 1.49 mm Hg *
m2/mL (interquartile ratio: 1.08-2.04 mm Hg * m2/mL). Stiffness was related to
mean pulmonary artery pressure (mPAP) (r2 = 0.33) and heart rate (r2 = 0.15) but
not to age or sex. Higher PA stiffness and higher pulmonary vascular resistance
(PVR) were documented in high-risk vs low-risk patients, as defined according to
the European Society of Cardiology/European Respiratory Society guidelines. The
dispersion of the PVR * C product was as variable as patient age and mPAP, and C
could not be estimated on the basis of PVR alone (95% limits of agreement of the
bias: -50% to 54%). Although transplant-free survival differed across PA
stiffness quartiles (P = .04), stiffness was not an independent predictor of long
term outcome (median follow-up duration: 2.43 years). CONCLUSIONS: In incident
idiopathic PAH, PA stiffness was related to mPAP and heart rate, and this finding
outperformed the potential influences of age and sex. Baseline PA stiffness did
not independently predict outcome. The great dispersion of the PVR * C product
implied that PVR and PA stiffness were differently affected by the disease
process.
PMID- 29940164
TI - The NHLBI LAM Registry: Prognostic Physiologic and Radiologic Biomarkers Emerge
From a 15-Year Prospective Longitudinal Analysis.
AB - BACKGROUND: The natural history of lymphangioleiomyomatosis (LAM) is mainly
derived from retrospective cohort analyses, and it remains incompletely
understood. A National Institutes of Health LAM Registry was established to
define the natural history and identify prognostic biomarkers that can help guide
management and decision-making in patients with LAM. METHODS: A linear mixed
effects model was used to compute the rate of decline of FEV1 and to identify
variables affecting FEV1 decline among 217 registry patients who enrolled from
1998 to 2001. Prognostic variables associated with progression to death/lung
transplantation were identified by using a Cox proportional hazards model.
RESULTS: Mean annual decline of FEV1 was 89 +/- 53 mL/year and remained
remarkably constant regardless of baseline lung function. FEV1 decline was more
rapid in those with greater cyst profusion on CT scanning (P = .02) and in
premenopausal subjects (118 mL/year) compared with postmenopausal subjects (74
mL/year) (P = .003). There were 26 deaths and 43 lung transplantations during the
evaluation period. The estimated 5-, 10-, 15-, and 20-year transplant-free
survival rates were 94%, 85%, 75%, and 64%, respectively. Postmenopausal status
(hazard ratio: 0.30; P = .0002) and higher baseline FEV1 (hazard ratio: 0.97; P =
.008) or diffusion capacity of lung for carbon monoxide (hazard ratio: 0.97; P =
.001) were independently associated with a lower risk of progression to death or
lung transplantation. CONCLUSIONS: The median transplant-free survival in
patients with LAM is > 20 years. Menopausal status, as well as structural and
physiologic markers of disease severity, significantly affect the rate of decline
of FEV1 and progression to death or lung transplantation in LAM.
PMID- 29940166
TI - Two-Year Results After AAV2-Mediated Gene Therapy for Choroideremia: The Alberta
Experience.
AB - PURPOSE: To assess the safety of a recombinant adeno-associated viral vector
expressing REP1 (rAAV2.REP1) in choroideremia subjects. METHODS: Design: Phase I
clinical trial. PARTICIPANTS: Six adult male subjects, 30-42 years of age, with
genetically confirmed choroideremia (CHM) were enrolled. The eye with the worse
vision, for all subjects, received a single subfoveal injection of 0.1 mL
rAAV2.REP1 containing 1011 genome particles. Subjects were followed up for 2
years thereafter. OUTCOME MEASURES: The primary outcome measure was safety,
determined by the number of ocular and systemic adverse events assessed by
ophthalmic examination, spectral-domain optical coherence tomography (SD-OCT),
and short-wavelength autofluorescence (FAF). Secondary outcome measures were the
change from baseline in best-corrected visual acuity (BCVA) in the treated eye
compared to the untreated eye, changes in visual function using microperimetry,
and the area of retinal pigment epithelium (RPE) preservation by FAF. RESULTS:
One subject had an 8-ETDRS-letter BCVA loss from baseline measured at 24 months,
while 1 subject had a >=15-letter BCVA gain. A similar improvement was noted in
the untreated eye of another subject throughout the follow-up period.
Microperimetry sensitivity showed no improvement or significant change up to 2
years after vector administration. The area of preserved RPE as measured by FAF
was noted to decline at a similar rate between the treated and untreated eyes.
One subject experienced a serious adverse event: a localized intraretinal immune
response, resulting in marked decline in visual function and loss of SD-OCT outer
retinal structures. CONCLUSIONS: One serious adverse event was experienced in 6
subjects treated with a subfoveal injection of AAV2.REP1. The area of remaining
functional RPE in the treated eye and untreated eye declined at the same rate
over a 2-year period. Fundus autofluorescence area is a remarkably predictive
biomarker and objective outcome measure for future studies of ocular gene therapy
in CHM subjects.
PMID- 29940165
TI - The Risk of Primary Open-Angle Glaucoma Following Vitreoretinal Surgery-A
Population-based Study.
AB - PURPOSE: To determine the risk of primary open-angle glaucoma (POAG) following
vitreoretinal surgery. DESIGN: Retrospective, population-based cohort study.
METHODS: All residents of Olmsted County, Minnesota, undergoing scleral buckle
and/or vitrectomy between 2004 and 2015 were included in the operative cohort.
The fellow nonoperative eyes were included in the comparison cohort. The study
and comparison cohorts consisted of 344 and 277 eyes, respectively. The main
outcome measure was the development of POAG. Secondary glaucomas were excluded.
The probability of glaucoma in operative eyes and nonoperative fellow eyes was
compared. The observed rate of POAG in the operative eyes was also compared to
the rate of POAG in the population of Olmsted County. RESULTS: The mean age was
64.7 years and the median follow-up period was 4.9 years. There were 58, 57, and
229 study eyes in the scleral buckle, scleral buckle with vitrectomy, and
vitrectomy only cohorts, respectively. The 10-year cumulative probability of
developing glaucoma was significantly greater in the operative group (8.9%, 95%
confidence interval [CI] 3.8%-14%) compared to the nonoperative group (1.0%, 95%
CI 0-2.4%; P = .02). None of the eyes in the scleral buckle group developed
glaucoma. The 10-year probability of POAG was 17.5% (95% CI 0-34.9%) and 10.0%
(95% CI 3.0%-17.0%) in the scleral buckle with vitrectomy and vitrectomy alone
cohorts, respectively. The rates of POAG in operative eyes undergoing scleral
buckle with vitrectomy and vitrectomy alone were significantly greater than the
rate of POAG for the Olmsted County general population (1.0%, P < .001).
CONCLUSIONS: The risk of POAG is increased after vitrectomy.
PMID- 29940167
TI - Retinal Anatomy and Electrode Array Position in Retinitis Pigmentosa Patients
After Argus II Implantation: An International Study.
AB - PURPOSE: To assess the retinal anatomy and array position in Argus II retinal
prosthesis recipients. DESIGN: Prospective, noncomparative cohort study. METHODS:
Setting: International multicenter study. PATIENTS: Argus II recipients enrolled
in the Post-Market Surveillance Studies. PROCEDURES: Spectral-domain optical
coherence tomography images collected for the Surveillance Studies (NCT01860092
and NCT01490827) were reviewed. Baseline and postoperative macular thickness,
electrode-retina distance (gap), optic disc-array overlap, and preretinal
membrane presence were recorded at 1, 3, 6, and 12 months. MAIN OUTCOME MEASURES:
Axial retinal thickness and axial gap along the array's long axis (a line between
the tack and handle); maximal retinal thickness and maximal gap along a B-scan
near the tack, midline, and handle. RESULTS: Thirty-three patients from 16
surgical sites in the United States and Germany were included. Mean axial retinal
thickness increased from month 1 through month 12 at each location, but reached
statistical significance only at the array midline (P = .007). The rate of
maximal thickness increase was highest near the array midline (slope = 6.02, P =
.004), compared to the tack (slope = 3.60, P < .001) or the handle (slope = 1.93,
P = .368). The mean axial and maximal gaps decreased over the study period, and
the mean maximal gap size decrease was significant at midline (P = .032). Optic
disc-array overlap was seen in the minority of patients. Preretinal membranes
were common before and after implantation. CONCLUSIONS: Progressive macular
thickening under the array was common and corresponded to decreased electrode
retina gap over time. By month 12, the array was completely apposed to the macula
in approximately half of the eyes.
PMID- 29940168
TI - Clinical Features of Central Serous Chorioretinopathy With Type 1 Choroidal
Neovascularization.
AB - PURPOSE: To evaluate the type 1 choroidal neovascularization (CNV) incidence and
associated factors in eyes with central serous chorioretinopathy (CSC). DESIGN:
Retrospective case series. METHODS: Records of 363 eyes (324 patients) with CSC
were reviewed. Age, sex, CSC type, choroidal vascular hyperpermeability (CVH),
best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SCT), and
systemic hypertension (HT) were assessed and compared between subjects with and
without neovascular CSC. RESULTS: We identified 219 and 144 eyes with chronic and
acute CSC, respectively. The mean participant age was 55.2 +/- 12.0 years, and 58
(15.6%) eyes had neovascular CSC. Age (no CNV: 54.8 +/- 12.1 years, CNV: 57.3 +/-
10.9 years; P = .118) and SCT (no CNV: 388.0 +/- 104.5 MUm, CNV: 377.4 +/- 108.9
MUm; P = .487) were comparable between eyes with and without CNV. However, BCVA
(logarithm of the minimum angle of resolution) was significantly worse in
subjects with CNV (0.28 +/- 0.33 [20/38] vs 0.15 +/- 0.29 [20/28]; P = .014).
Neovascular CSC occurred more often in women (72 [23.6%] vs 20 [34.5%], P = .099)
and in cases of chronic CSC (171 [56.1%] vs 48 [82.8%], P < .001), CVH (205
[67.2%] vs 58 [100%], P < .001), and HT (91 [29.8%] vs 24 [41.4%], P = .092).
Chronic CSC (P = .001), female sex (P = .075), and poor BCVA (P = .091) were
associated with neovascular CSC (multiple regression). CONCLUSIONS: Chronic CSC,
female sex, CVH, and poor BCVA are risk factors for CNV in eyes with CSC.
PMID- 29940169
TI - Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty Grafts
With Endothelium Tri-Folded Inwards.
AB - PURPOSE: To evaluate the initial outcomes and complications of Descemet membrane
endothelial keratoplasty (DMEK) using donor tissues tri-folded with the
endothelium inwards, preloaded at the Eye Bank, and delivered with bimanual pull
through technique. DESIGN: Prospective, noncomparative, interventional case
series. METHODS: Setting: Eye bank and tertiary care eye department. PATIENT
POPULATION: Forty-six consecutive eyes of 41 patients with Fuchs endothelial
dystrophy with or without cataract operated between November 2016 and March 2017.
INTERVENTION: DMEK tissues prepared with SCUBA technique and punched to a
diameter of 8.25 mm were preloaded with the endothelium tri-folded inwards in an
intraocular lens (IOL) cartridge with a 2.2-mm opening filled with the same
tissue culture medium contained in the vial used for shipment to the surgeon.
Standardized DMEK was performed as a single procedure (n = 15) or in combination
with phacoemulsification and IOL implantation (n = 31) within 48 hours from
preparation using a bimanual pull-through technique. MAIN OUTCOME MEASURES:
Preparation and surgical times, intraoperative and postoperative complications,
best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD),
and graft detachment rate. RESULTS: Preparation time averaged 26.2 +/- 4.1
minutes (range 17-36 minutes), while the surgical time from opening of the
stoppers to air fill of the anterior chamber never exceeded 9 minutes (range 3-9
minutes). Surgery was uneventful in all cases. Postoperative complications
included graft detachment in 9 of 46 cases (19.6%), successfully managed in all
cases by single rebubbling within 6 days from surgery, and glaucoma irresponsive
to conservative treatment in 1 of 46 cases (2.1%). In all eyes without
comorbidities (35 of 40 eyes) BSCVA was 20/25 (0.097 logMAR) or better as early
as 3 months after surgery. Six months postoperatively, ECD was available in 24 of
25 eyes with an endothelial cell loss calculated as a percentage of the
preoperative value determined at the eye bank (ranging from 2500 to 2800
cells/mm2) of 29.5% +/- 14.8% (range 8.3%-52.1%). CONCLUSIONS: Delivering a
preloaded DMEK tissue, tri-folded with the endothelium inwards, minimizes
surgical time and costs without negatively affecting the outcomes of the
procedure.
PMID- 29940170
TI - MicroRNA: A new generation therapeutic target in diabetic nephropathy.
AB - Diabetic nephropathy (DN) is one of the most prevalent lethal complications of
diabetes that leads to end stage renal disease. Although several clinical
approaches exist to attenuate DN, there is not curative treatment to date. DN is
complicated, as it involves several simultaneous molecular pathways. Some natural
and synthetic molecules have been reported to inhibit some specific pathogenic
signal transduction in DN. However, the complications of DN still remain
uncontrolled. MicroRNAs (miRNAs) are a class of non-coding RNAs that can bind to
the 3'UTR of their target mRNAs to participate in epigenetic regulation of their
downstream signalling molecules. Therefore, miRNAs have a potential role in
regulating the pathogenesis of several diseases. Recent studies have identified
the roles of several miRNAs in the signalling cascade involved in DN
pathophysiology. Therefore, miRNAs are an attractive therapeutic target in DN.
However, further research is needed to identify the key miRNAs in DN and their
specific functions at both the transcriptional and translational levels. This
review aimed to provide current information for different miRNAs involved in DN
and to provide the future probabilities of miRNA-based therapies in DN.
PMID- 29940171
TI - A 5-hydroxyoxindole derivative attenuates LPS-induced inflammatory responses by
activating the p38-Nrf2 signaling axis.
AB - 5-Hydroxyoxindole is a urinary metabolite of indole that exhibits antioxidant
activity. In the present study, we found that a 5-hydroxyoxindole derivative (5
HI) significantly inhibited LPS-induced inflammatory effects in the murine
macrophage cell line, RAW264.7. 5-HI induced the expression of the transcription
factor, Nrf2, which is typically ubiquitinated by Keap1, an adaptor component of
the ubiquitin E3 ligase complex, resulting in its proteasomal degradation. By
utilizing Keap1-/- MEFs reconstituted with Keap1 mutants harboring substitutions
in their major cysteine residues, we clarified the importance of Cys151 in Keap1
as a sensor for 5-HI in the induction of Nrf2 expression. Furthermore, 5-HI
induced the activation of the MKK3/6-p38 pathway, which is required for the
transcriptional activation of Nrf2. The knockdown of Nrf2 enhanced the LPS
induced expression of inflammatory mediators, including iNOS, NO, and CCL2, and
effectively repressed the inhibitory effects of 5-HI on their expression.
Although 5-HI and antioxidant N-acetyl cysteine (NAC) both reduced LPS-induced
ROS generation, the treatment with NAC did not affect the LPS-induced expression
of inflammatory mediators, suggesting that the anti-inflammatory activity of 5-HI
mediated by Nrf2 is independent of redox control. Furthermore, when injected into
mice with 5-HI, the expression of Nrf2 was significantly increased, and the LPS
induced mRNA expression of CXCL1, CCL2, TNFalpha, and IL-6 were remarkably
inhibited in the kidneys, liver, and lungs, and the production of these cytokines
in serum was effectively reduced. Collectively, these results suggest that 5-HI
has potential in the treatment of inflammatory diseases through the activation of
Nrf2.
PMID- 29940172
TI - Appraising the "entourage effect": Antitumor action of a pure cannabinoid versus
a botanical drug preparation in preclinical models of breast cancer.
AB - Breast cancer is the second leading cause of death among women. Although early
diagnosis and development of new treatments have improved their prognosis, many
patients present innate or acquired resistance to current therapies. New
therapeutic approaches are therefore warranted for the management of this
disease. Extensive preclinical research has demonstrated that cannabinoids, the
active ingredients of Cannabis sativa, trigger antitumor responses in different
models of cancer. Most of these studies have been conducted with pure compounds,
mainly Delta9-tetrahydrocannabinol (THC). The cannabis plant, however, produces
hundreds of other compounds with their own therapeutic potential and the
capability to induce synergic responses when combined, the so-called "entourage
effect". Here, we compared the antitumor efficacy of pure THC with that of a
botanical drug preparation (BDP). The BDP was more potent than pure THC in
producing antitumor responses in cell culture and animal models of ER+/PR+, HER2+
and triple-negative breast cancer. This increased potency was not due to the
presence of the 5 most abundant terpenes in the preparation. While pure THC acted
by activating cannabinoid CB2 receptors and generating reactive oxygen species,
the BDP modulated different targets and mechanisms of action. The combination of
cannabinoids with estrogen receptor- or HER2-targeted therapies (tamoxifen and
lapatinib, respectively) or with cisplatin, produced additive antiproliferative
responses in cell cultures. Combinations of these treatments in vivo showed no
interactions, either positive or negative. Together, our results suggest that
standardized cannabis drug preparations, rather than pure cannabinoids, could be
considered as part of the therapeutic armamentarium to manage breast cancer.
PMID- 29940174
TI - Functional pharmacogenomics and toxicity of PolyPurine Reverse Hoogsteen hairpins
directed against survivin in human cells.
AB - PolyPurine Reverse Hoogsteen (PPRH) hairpins constitute a relatively new
pharmacological agent for gene silencing that has been applied for a growing
number of gene targets. Previously we reported that specific PPRHs against the
antiapoptotic gene survivin were able to decrease viability of PC3 prostate
cancer cells by increasing apoptosis, while not acting on HUVEC non-tumoral
cells. These PPRHs were efficient both in vitro and in vivo. In the present work,
we performed a functional pharmacogenomics study on the effects of specific and
unspecific hairpins against survivin. Incubation of PC3 cells with the specific
HpsPr-C-WT led to 244 differentially expressed genes when applying the p < 0.05,
FC > 2, Benjamini-Hochberg filtering. Importantly, the unspecific or control Hp
WC did not originate differentially expressed genes using the same settings. Gene
Set Enrichment Analysis (GSEA) revealed that the differentially expressed genes
clustered very significantly within the gene sets of Regulation of cell
proliferation, Cellular response to stress, Apoptosis and Prostate cancer.
Network analyses using STRING identified important interacting gene-nodes within
the response of PC3 cells to treatment with the PPRH against survivin, mainly
POLR2G, PAK1IP1, SMC3, SF3A1, PPARGC1A, NCOA6, UGT2B7, ALG5, VAMP7 and HIST1H2BE,
the former six present in the Gene Sets detected in the GSEA. Additionally, HepG2
and 786-O cell lines were used to carry out in vitro experiments of
hepatotoxicity and nephrotoxicity, respectively. The unspecific hairpin did not
cause toxicity in cell survival assays (MTT) and produced minor changes in gene
expression for selected genes in RT-qPCR arrays specifically developed for
hepatic and renal toxicity screening.
PMID- 29940173
TI - Pharmacological characterization of the neurotrophic sesquiterpene jiadifenolide
reveals a non-convulsant signature and potential for progression in
neurodegenerative disease studies.
AB - The 'neurotrophic sesquiterpenes' refer to a group of molecules derived from the
Illicium genus of flowering plant. They display neurotrophic effects in cultured
neuron preparations and have been suggested to be cognitive enhancers and
potential therapeutics for neurodegenerative disorders and dementias. Recent
synthetic advances generated sufficient quantities of jiadifenolide for in vivo
investigation into its biological effects. Jiadifenolide did not induce
convulsions in mice nor did it enhance or diminish convulsions induced by
pentylenetetrazole. Other negative allosteric modulators of GABAA receptors,
picrotoxin, tetramethylenedisulfotetramine (TETS), and bilobalide all induced
convulsions. Either i.p. or i.c.v. dosing generated micromolar plasma and brain
levels of jiadifenolide but only small effects on locomotion of mice. However,
jiadifenolide decreased d-amphetamine-induced hyperlocomotion in mice, an
antipsychotic-like drug effect. Jiadifenolide did not significantly alter body
temperature or behavior in the forced-swim test in mice. Molecular simulation
data suggested a potential site in the pore/M2 helix region that is at an
overlapping, yet lower position than those observed for other 'cage convulsant'
compounds such as TETS and picrotoxin. We hypothesize that a position nearer to
the entrance of the pore channel may allow for easier displacement of
jiadifenolide from its blocking location leading to lower potency and lower side
effect liability. Like jiadifenolide, memantine (Namenda), one of the few drugs
used in the symptomatic treatment of dementias, occupies a unique site on the
NMDA receptor complex that creates low binding affinity that is associated with
its reduced side-effect profile. Given the potential therapeutic applications of
jiadifenolide and its relatively inert effects on overt behavior, the possibility
of clinical utility for jiadifenolide and related compounds becomes intriguing.
PMID- 29940175
TI - The inhibitors of soluble adenylate cyclase 2-OHE, KH7, and bithionol compromise
mitochondrial ATP production by distinct mechanisms.
AB - Soluble adenylate cyclase (sAC) is a non-plasma membrane-bound isoform of the
adenylate cyclases signaling via the canonical second messenger, 3',5'-cyclic AMP
(cAMP). sAC is involved in key physiological processes such as insulin release,
sperm motility, and energy metabolism. Thus, sAC has attracted interest as a
putative drug target and attempts have been made to develop selective inhibitors.
Since sAC has a binding constant for its substrate, ATP, in the millimolar range,
reductions in mitochondrial ATP production may be part of the mechanism-of-action
of sAC inhibitors and the potential of these compounds to study the physiological
outcomes of inhibition of sAC might be severely hampered by this. Here, we
evaluate the effects of two commonly employed inhibitors, 2-OHE and KH7, on
mitochondrial ATP production and energy metabolism. For comparison, we included a
recently identified inhibitor of sAC, bithionol. Employing mitochondria isolated
from mouse brain, we show that all three compounds are able to curb ATP
production albeit via distinct mechanisms. Bithionol and KH7 mainly inhibit ATP
production by working as a classical uncoupler whereas 2-OHE mainly works by
decreasing mitochondrial respiration. These findings were corroborated by
investigating energy metabolism in acute brain slices from mice. Since all three
sAC inhibitors are shown to curb mitochondrial ATP production and affect energy
metabolism, caution should be exercised when employed to study the physiological
roles of sAC or for validating sAC as a drug target.
PMID- 29940176
TI - Membrane cholesterol modulates STEAP2 conformation during dynamic intracellular
trafficking processes leading to broad subcellular distribution.
AB - STEAP2 is a member of the Six-Transmembrane Epithelial Antigen of the Prostate
(STEAP) protein family that is proposed to function as metalloreductase. While
STEAP2 shows a complex subcellular distribution pattern localizing to both
secretory and endocytic pathway organelles, how such broad steady-state
distribution is maintained is unknown. Similarly, whether STEAP2 undergoes any
compartment-specific modulation during intracellular trafficking has not been
reported. Leveraging a newly-identified monoclonal antibody that recognizes a
conformation-sensitive epitope nested in the second extracellular loop of STEAP2,
we demonstrate that the epitope formation was dependent on the cholesterol
content of the membrane in which STEAP2 was embedded. Monitoring the STEAP2
dependent internalization of this antibody uncovered STEAP2's rapid
internalization from the cell surface and their subsequence trafficking to the
Golgi region and endosome-like puncta. Acute inhibition of endocytosis also
increased the detectable amount of STEAP2 at the plasma membrane. Collectively,
these experiments demonstrate that an intricate balance of membrane flux between
the secretory and endocytic pathways underlies the characteristic broad
subcellular localization of STEAP2. By using a cell-based assay that detects the
metalloreductase functions of cell surface-localizing STEAP4, STEAP2's
metalloreductase activities were not detectable, suggesting that its enzymatic
function is suppressed at the plasma membrane. The conformational modulation of
STEAP2 by the local membrane cholesterol content can therefore serve as a
potential mechanism to modulate STEAP2 function in a compartment-restricted
manner, by coupling a pre-existing difference in cholesterol content among
different cellular membranes to a dynamic trafficking process leading to broad
subcellular distribution.
PMID- 29940177
TI - Rnd3/RhoE expression is regulated by G-actin through MKL1-SRF signaling pathway.
AB - Rnd3/RhoE is an atypical member of the Rho family of small GTPases, devoid of
intrinsic GTP hydrolytic activity and a general modulator of important cellular
processes such as migration and proliferation. Here, we show that Rnd3 is a
target of the transcription factor SRF and its co-activator MKL1. The MKL1-SRF
pathway assures the translation of physical forces into a transcriptional
response. Rho GTPases can modulate the activity of this mechanotransduction
pathway through actin cytoskeleton regulation, and many MKL1-SRF targets are
involved in the regulation of actin. We found that Rnd3 expression is altered by
G-actin signaling and sensitive to actin-targeting drugs and MKL1 mutants. We
further characterized a consensus SRF binding site in the Rnd3 promoter. We found
that MKL1-SRF modulation regulates Rnd3 promoter activity and Rnd3 expression can
affect MKL1-SRF pathway activity in return. We demonstrated that this novel MKL1
SRF target is required in mechanosensitive mechanisms such as cell spreading and
spheroid formation. Thus, Rnd3 is a MKL1-SRF target that plays a key role in the
feedback loop described between the MKL1-SRF pathway and the organization of the
actin cytoskeleton.
PMID- 29940178
TI - Staphylococcal enterotoxin C2 stimulated the maturation of bone marrow derived
dendritic cells via TLR-NFkappaB signaling pathway.
AB - As a kind of superantigen, staphylococcal enterotoxin C2 (SEC2) is well known as
a powerful immunomodulator. However, most previous studies about SEC2 focus on
its T cell activating characters. But the direct effect of SEC2 on antigen
presenting cells (APCs) which are important for the T cell activation is not
clearly. In this study, we investigated the effect of SEC2 on murine bone marrow
derived dendritic cells (BMDCs) which are known as the specialized professional
APCs. Contrary to its effects on T cells, SEC2 could not induce proliferation or
cytotoxicity to BMDCs even in high concentrations. While SEC2 could promote the
mature of BMDCs with increased expression of co-stimulatory molecules on cell
membrane such as CD80, CD86, and MHC II. The production of pro-inflammatory
cytokines such as TNF-alpha, IFN-gamma and IL-6 were also increased in BMDCs
treated with SEC2. We also found that SEC2 enhanced the genes expression of
pattern recognition receptors including toll-like receptors 2 (TLR2) and TLR4 in
BMDCs, and up-regulated the key signal molecule MyD88 in both mRNA and protein
levels. In addition, SEC2 also caused IkappaBalpha degradating and NFkappaB p65
translocating from the cytoplasm to the nucleus in BMDCs. The siRNAs for both
TLR2 and TLR4, as well as NFkappaB specific inhibitor BAY 11-7085 could inhibit
the co-stimulatory molecules expression and pro-inflammatory cytokines releasing
induced by SEC2. Moreover, TLR2/4 specific siRNAs inhibited p65 and MyD88
upregulation induced by SEC2. In summary, all our results indicated that SEC2
could stimulate BMDCs maturation through TLR-NFkappaB signaling pathways.
PMID- 29940179
TI - Model Protein Adsorption on Polymers Explained by Hansen Solubility Parameters.
AB - Hansen solubility parameters (HSP) theory has been successful in explaining the
wettability of organic solvents on polymer surfaces and miscibility of different
polymers. Here, we demonstrate that the amount of bovine serum albumin (BSA)
protein adsorption on different polymer surfaces can also be explained by HSP.
Interestingly, the HSP of the adsorbed BSA proteins calculated from the protein
adsorption data is different than the HSP of native BSA protein itself. The HSP
of the adsorbed BSA proteins are more hydrophobic than the native BSA protein.
This observation suggested adsorbed BSA proteins are partially denatured and
exposed their hydrophobic core toward the polymer surfaces. These results
highlight a new strategic direction to understand interaction of protein with a
surface: a theoretical approach that compliments experimental approach. The model
in this study could be used to predict the amount of BSA adsorption on a polymer
or any other solid surface, if the HSP of that surface is known. Further, the
model can serve as a prescreen method to identify surfaces that are problematic
at the outset and inform subsequent empirical studies to select packaging that
will have the least adsorption for the specific biologic application.
PMID- 29940180
TI - Thermodynamic Evaluation of the Interaction Driven by Hydrophobic Bonding in the
Aqueous Phase.
AB - In the present study, the interaction between phenobarbital and activated carbons
which is driven by hydrophobic bonding was evaluated. The Two-Mechanism Langmuir
Like Equation was proposed to describe the isotherms for phenobarbital adsorbing
to activated carbons. The parameters in the Two-Mechanism Langmuir-Like Equation
obtained from the nonlinear fitting of isotherms were used in the calculations of
the differential Gibbs free energy for the hydrophobic bonding-driven
interaction. Two thermodynamic models, the Modified Crisp Model and the van't
Hoff Equation, were adopted to estimate the differential Gibbs free energy. And,
comparing the differential Gibbs free energy obtained from the 2 thermodynamic
relationships, it can be determined that an adsorbing phenobarbital molecule
displaces 12 water molecules on the hydrocarbon surfaces of the activated carbons
(hydrophobic bonding case). The difference between the estimates of the
differential Gibbs free energy obtained by the Modified Crisp Model and by the
van't Hoff Equation provides a new experimental method to calculate the number of
solvent molecules displaced by an adsorbing solute molecule. This is a completely
general technique for the hydrophobic bonding-driven interaction and is not
limited to the systems studied. The calculated positive differential entropy
confirmed that the adsorption process was entropy driven.
PMID- 29940181
TI - Amphotericin B-Loaded Poly(lactic-co-glycolic acid) Nanofibers: An Alternative
Therapy Scheme for Local Treatment of Vulvovaginal Candidiasis.
AB - Vulvovaginal candidiasis is an inflammation localized in the vulvovaginal area.
It is mostly caused by Candida albicans. Its treatment is based on the systemic
and local administration of antifungal drugs. However, this conventional therapy
can fail owing to the resistance of the Candida species and noncompliance of
patients. Amphotericin B-loaded poly(lactic-co-glycolic acid) nanofibers are
single-use, antifungal, controlled drug delivery systems, and represent an
alternative therapeutic scheme for the local treatment of vulvovaginal
candidiasis. Nanofibers were characterized by analytical techniques and with an
in vitro drug delivery study. In vitro and in vivo fungicidal activity of
amphotericin B released from nanofibers was evaluated using the agar diffusion
method and an experimental murine model of vulvovaginal candidiasis,
respectively. Analytical techniques showed that amphotericin B was physically
mixed in the polymeric nanofibers. Nanofibers controlled the delivery of
therapeutic doses of amphotericin B for 8 consecutive days, providing effective
in vitro antifungal activity and eliminated the in vivo vaginal fungal burden
after 3 days of treatment and with only one local application. Amphotericin B
loaded poly(lactic-co-glycolic acid) nanofibers could be potentially applied as
an alternative strategy for the local treatment of vulvovaginal candidiasis
without inducing fungal resistance, yet ensuring patient compliance.
PMID- 29940182
TI - The anorectic effect of central PYY1-36 treatment in rainbow trout (Oncorhynchus
mykiss) is associated with changes in mRNAs encoding neuropeptides and parameters
related to fatty acid sensing and metabolism.
AB - We hypothesized that peptide YY (PYY) is involved in the metabolic regulation of
food intake in fish. Therefore, we assessed in rainbow trout (Oncorhynchus
mykiss) the effects of intracerebroventricular treatment with 10 ng/g PYY1-36 on
food intake, expression of neuropeptides involved in food intake control, and the
activity of fatty acid-sensing systems. The administration of PYY1-36 caused a
significant reduction in food intake up to 24 h post-treatment. This anorectic
action was associated with changes 2 h after treatment in mRNA abundance of
neuropeptides involved in metabolic regulation of food intake in hypothalamus
(decreased NPY and raised CART values) and hindbrain (increased POMCa1 values).
We also observed that PYY1-36 treatment induced changes in mRNA abundance of
parameters related to fatty acid sensing and metabolism in hypothalamus
(decreased values of ACLY, PPARgamma, and SREBP1c) and hindbrain (increased
values of LPL, FAT/CD36, PPARalpha, PPARgamma, and SREBP1c and decreased values
of UCP2a). PYY1-36 treatment also increased mRNA abundance of mTOR. In general,
it seems that mRNAs encoding some components of the machinery required for fatty
acid sensing and metabolism are activated by PYY1-36. The response observed was
higher in the hindbrain than in the hypothalamus, supporting the greater
importance of this brain area in mediating the modulatory effects of
gastrointestinal hormones on feeding regulation.
PMID- 29940183
TI - Effects of heavy metals identified in Chascomus shallow lake on the endocrine
reproductive axis of pejerrey fish (Odontesthes bonariensis).
AB - Some heavy metals related to human activities were measured in the water of
Chascomus lake. The maximum concentrations were: 0.23 MUg/L for Cd, 4.28 MUg/L
for Cr, 22.09 MUg/L for Cu, 2.49 MUg/L for Ni, 3.24 MUg/L for Pb and 210.76 MUg/L
for Zn. The values of Cd, Cr, Cr, Pb and Zn were above the Argentine National
Guidelines for the Protection of the Aquatic life. The analysis of gonadal
condition of pejerrey fish (Odontesthes bonariensis) from this lake did not
revealed any reproductive damages. However, exposures with environmental
concentrations of Cd, Cr, Cu and Zn under laboratory conditions of pejerrey males
(14 days), caused a significant increase of the expression of the three variants
of gnrh in the brain (within Cd exposure) and a decrease in cyp19a1b mRNA (within
Cu exposure). Furthermore, at pituitary level, a decrease in fshb transcript
levels was observed in the fish exposed to Cd and Cr and a decrease in the
expression of both gonadotropin receptors at gonadal level in Zn exposure.
Moreover, the gonads of the fish exposed to all the tested metals suffered
structural damages showing shortness of the spermatic lobules, fibrosis, testis
ova and the presence of piknotic cells. All these findings alert that heavy
metals pollution affects the expression of key reproductive genes and gonadal
structure of fish species that represent the predominant group of organisms and
are considered sentinel species in the aquatic ecosystems.
PMID- 29940184
TI - High levels of circulating prostaglandin F2alpha associated with ovulation
stimulate female sexual receptivity and spawning behavior in the goldfish
(Carassius auratus).
AB - This study tested the hypothesis that blood-borne prostaglandin F2alpha
(PGF2alpha) produced at the time of ovulation by female goldfish, a typical
scramble-spawning, egg-laying cyprinid fish, functions as a hormone which
stimulates female sexual receptivity, behavior, and pheromone release, thereby
synchronizing female mating behavior with egg availability. We conducted 5
experiments. First, we tested whether PGF2alpha is found in the blood of female
fish and if it increases at the time of ovulation. Using gas chromatography-mass
spectrometry, we found that circulating PGF2alpha was approximately 1 ng/ml prior
to ovulation, increased over 50-fold within 3 h of ovulation and returned to
preovulatory values after spawning and egg release. Ovulated fish also released
over 2 ng/h of PGF2alpha and 800 ng/h of 15-keto-PGF2alpha, a metabolite of
PGF2alpha - both compounds with known pheromonal function. Second, we tested how
closely levels of circulating PGF2alpha tracked the timing of ovulation by
sampling fish at the time of ovulation and discovered that PGF2alpha increased
within 15 min of ovulation, peaked after 9 h, and fell to basal levels as fish
spawned and released their eggs. Third, we tested whether an interaction between
eggs and the reproductive tract serves as a source of circulating PGF2alpha and
its relationship with female sexual receptivity by injecting ovulated eggs (or an
egg-substitute) into the reproductive tract of females stripped of ovulated eggs.
We found both of these treatments elicited measurable increases in plasma
PGF2alpha as well as female sexual behavior. A fourth experiment showed that
indothemacin, a PG synthase inhibitor, blocked both PGF2alpha increase and female
sexual behavior in egg-substitute-injected fish. Finally, we tested the
relationship between the expression of female behavior and PGF2alpha in PGF2alpha
injected fish and found that circulating PGF2alpha levels closely paralleled
behavior, rising within 15 min and peaking at 45 min. Together, these experiments
establish that PGF2alpha functions as a behavioral blood-borne hormone in the
goldfish, suggesting it likely has similar activity in other related, externally
fertilizing fishes.
PMID- 29940185
TI - Molecular Mechanisms of RNA Targeting by Cas13-containing Type VI CRISPR-Cas
Systems.
AB - Prokaryotic adaptive immune systems use Clustered Regularly Interspaced Short
Palindromic Repeats (CRISPRs) and CRISPR-associated (Cas) proteins for RNA-guided
cleavage of foreign genetic elements. The focus of this review, Type VI CRISPR
Cas systems, contain a single protein, Cas13 (formerly C2c2) that when assembled
with a CRISPR RNA (crRNA) forms a crRNA-guided RNA-targeting effector complex.
Type VI CRISPR-Cas systems can be divided into four subtypes (A-D) based on Cas13
phylogeny. All Cas13 proteins studied to date possess two enzymatically distinct
ribonuclease activities that are required for optimal interference. One RNase is
responsible for pre-crRNA processing to form mature Type VI interference
complexes, while the other RNase activity provided by the two Higher Eukaryotes
and Prokaryotes Nucleotide-binding (HEPN) domains, is required for degradation of
target-RNA during viral interference. In this review, I will compare and contrast
what is known about the molecular architecture and behavior of Type VI (A-D)
CRISPR-Cas13 interference complexes, how this allows them to carry out their RNA
targeting function, how Type VI accessory proteins are able to modulate Cas13
activity, and how together all of these features have led to the rapid
development of a range of RNA-targeting applications. Throughout I will also
discuss some of the outstanding questions regarding Cas13's molecular behavior,
and its role in bacterial adaptive immunity and RNA-targeting applications.
PMID- 29940186
TI - Mechanistic Insights into Recognitions of Ubiquitin and Myosin VI by Autophagy
Receptor TAX1BP1.
AB - TAX1BP1, a ubiquitin-binding adaptor, plays critical roles in the innate immunity
and selective autophagy. During autophagy, TAX1BP1 may not only function as an
autophagy receptor to recruit ubiquitylated substrates for autophagic
degradation, but also serve as a Myosin VI cargo adaptor protein for mediating
the maturation of autophagosome. However, the mechanistic basis underlying the
specific interactions of TAX1BP1 with ubiquitin and Myosin VI remains elusive.
Here, using biochemical, NMR and structural analyses, we elucidate the detailed
binding mechanism and uncover the key determinants for the interaction between
TAX1BP1 and ubiquitin. In addition, we reveal that both tandem zinc-fingers of
TAX1BP1 and the conformational rigidity between them are required for the Myosin
VI binding of TAX1BP1, and ubiquitin and Myosin VI are mutually exclusive in
binding to TAX1BP1. Collectively, our findings provide mechanistic insights into
the dual functions of TAX1BP1 in selective autophagy.
PMID- 29940187
TI - ABCB6 Resides in Melanosomes and Regulates Early Steps of Melanogenesis Required
for PMEL Amyloid Matrix Formation.
AB - Genetically inheritable pigmentation defects provide a unique opportunity to
reveal the function of proteins contributing to melanogenesis. Dyschromatosis
universalis hereditaria (DUH) is a rare pigmentary genodermatosis associated with
mutations in the ABCB6 gene. Here we use optical and electron microscopy imaging
combined with biochemical tools to investigate the localization and function of
ABCB6 in pigment cells. We show that ABCB6 localizes to the membrane of early
melanosomes and lysosomes of the human melanocytic cell line MNT-1. Depletion of
ABCB6 by siRNA impaired PMEL amyloidogenesis in early melanosomes and induced
aberrant accumulation of multilamellar aggregates in pigmented melanosomes. PMEL
fibril formation and normal maturation of pigmented melanosomes could be restored
by the overexpression of wild-type ABCB6 but not by variants containing an
inactivating catalytic mutation (K629M) or the G579E DUH mutation. In line with
the impairment of PMEL matrix formation in the absence of ABCB6, morphological
analysis of the retinal pigment epithelium of ABCB6 knockout mice revealed a
significant decrease of melanosome numbers. Our study extends the localization of
ABCB6 to melanosomes, suggesting a potential link between the function of ABCB6
and the etiology of DUH to amyloid formation in pigment cells.
PMID- 29940188
TI - Antibacterial and antifungal activity of phytosterols and methyl dehydroabietate
of Norway spruce bark extracts.
AB - The current study focuses on the analysis of in vitro biological activity of
extract from bark of Norway spruce (Picea Abies), which can find potential
application in food and cosmetic industry and pharmacology. Milled bark was
subjected to Soxhlet extraction and supercritical fluid extraction to obtain two
ethanol extracts. These extracts were further used to obtain their pre-extracts
to n-hexane. It was investigated whether beta-sitosterol exhibits bacteriostatic
activity necessary to observe antimicrobial and antifungal activity of methyl
dehydroabiatate. This synergic effect and bacteriostatic activity of beta
sitosterol have not been previously reported. The greatest inhibition zone of n
hexane pre-extracts was confirmed in bacterium Pseudomonas aeruginosa (0,9 - 1,5
cm) and yeast Alternaria alternata (0,7 - 1,6 cm). It is novel, the antioxidant,
antimicrobial and antifungal activity of spruce bark extracts assessed in terms
of food and cosmetic fortification.
PMID- 29940189
TI - RGNNV-induced cell cycle arrest at G1/S phase enhanced viral replication via p53
dependent pathway in GS cells.
AB - Nervous necrosis virus (NNV) is a ubiquitous pathogen in the aquaculture
worldwide. Little is known about the relationship between NNV virus and host
cells. Our studies showed that RGNNV infection could induce cell cycle arrest via
activation of p53 signaling in cultured host cells. Infection of RGNNV
redistributed NPM1, stabilized p53 and inhibited cell proliferation by inducing
G1 arrest. RGNNV infection also led to phosphorylation and accumulation of p53 in
a time-dependent manner. Furthermore, RGNNV infection upregulated cyclin
dependent kinase inhibitor 1 A (p21) and downregulated cyclin E and cyclin
dependent kinase 2 (CDK2). The expression of genes in the p53 pathway did not
change significantly after p53 knockdown by pifithrin-alpha during RGNNV
infection. However, NPM1 knockdown could abrogate RGNNV-induced cell
proliferation inhibition, activation of p53 signaling and cell cycle arrest. In
addition, RGNNV infection of the cells synchronized in various stages of cell
cycle showed that viral genomic RNA and virus titer were higher in the cells
released from G1 phase- or S phase-synchronized cells than that in the cells
released from the G2 phase-synchronized or asynchronous cells after 18 h p.i.
Therefore, our study reveals that RGNNV infection induces the p53-dependent
pathway, resulting in a cell cycle arrest at G1 phase in host cells, which might
provide a favorable condition for viral replication.
PMID- 29940190
TI - Porcine deltacoronavirus induces caspase-dependent apoptosis through activation
of the cytochrome c-mediated intrinsic mitochondrial pathway.
AB - Porcine deltacoronavirus (PDCoV), a newly discovered enteric coronavirus, is a
causative agent of severe clinical diarrhea and intestinal pathological damage in
piglets. As a first step toward understanding the effect of PDCoV on host cells,
we elucidated mechanisms underlying the process of apoptotic cell death after
PDCoV infection. The use of a pan-caspase inhibitor resulted in the inhibition of
PDCoV-induced apoptosis and reduction of PDCoV replication, suggestive of the
association of a caspase-dependent pathway. Furthermore, PDCoV infection
necessitated the activation of the initiator caspase-9 responsible for the
intrinsic mitochondrial apoptosis pathway. Experimental data indicated that PDCoV
infection led to Bax-mediated mitochondrial outer membrane permeabilization
(MOMP), resulting in specific relocation of the mitochondrial cytochrome c (cyt
c) into the cytoplasm. Treatment with cyclosporin A (CsA), an inhibitor of
mitochondrial permeability transition pore (MPTP) opening, significantly
suppressed PDCoV-triggered apoptosis and viral replication. Moreover, cyt c
release was completely abrogated in PDCoV-infected cells in the presence of CsA,
suggesting the critical role of MPTP in intrinsic apoptosis in response to PDCoV
infection. Altogether, our results indicate that PDCoV infection stimulates MOMP
either via Bax recruitment or MPTP opening to permit the release of apoptogenic
cyt c into the cytoplasm, thereby leading to execution of the caspase-dependent
intrinsic apoptosis pathway to facilitate viral replication in vitro.
PMID- 29940192
TI - Adaptation of reflexive fusional vergence is directionally biased.
AB - Divergence is known to differ from convergence across a wide range of clinical
parameters. We have postulated that a limited neural substrate results in reduced
fusional divergence velocities and subsequently a reduced capacity to adapt tonic
vergence to uncrossed disparities. We further investigated this hypothesis by
characterizing the degree of plasticity in reflexive fusional vergence to
repetitive end-point errors using a disparity-based double-step paradigm. 10
adults completed 4 study visits where reflexive fusional convergence or
divergence was measured (250 Hz infrared oculography) to a 2 degrees disparity
step and then lengthened or shortened via a repeated double-step (2 degrees +/-
1.5 degrees ). Stimuli were presented dichoptically at 40 cm. Adaptive
modification of vergence responses was similar between directions for the
shortening conditions, suggesting a common neural mechanism responds to
overshooting errors. In comparison, adaptive lengthening of convergence was
slower, but of equal magnitude, suggesting a second neural mechanism with a
longer time constant for undershooting errors. Divergence response velocities
were slower at baseline and did not increase after adaptive lengthening. Instead,
increases in divergence response amplitudes were a result of increased response
duration, implying saturation of the reflexive, preprogrammed response. Adaptive
responses serving to increase or decrease reflexive fusional vergence recruitment
were asymmetric. Adaptive lengthening of convergence and divergence identified
further directional asymmetries. The results support the hypothesis that the
neural substrate underlying divergence is attenuated, resulting in reduced
reflexive plasticity when compared to convergence. The clinical and technological
implications of these results are discussed.
PMID- 29940191
TI - Comparison of symmetrical prism adaptation to asymmetrical prism adaptation in
those with normal binocular vision.
AB - This study sought to determine whether symmetrical compared to asymmetrical
horizontal prisms (base-out or base-in) evoked different rates of phoria
adaptation. Sixteen young adults with normal binocular vision participated in a
symmetrical phoria adaptation experiment using a 3Delta base-out or 3Delta base
in binocular prism flipper and an asymmetrical phoria adaptation experiment using
a 6Delta base-out or 6Delta base-in monocular wedge prism. The experiments were
randomized and counterbalanced to reduce the influence of the prism stimulation
order. Asymmetrical base-out prism adaptation was significantly faster than
symmetrical prism adaptation for subjects with normal binocular vision.
Asymmetrical phoria adaptation with base-in prism was not significantly different
from symmetrical phoria adaptation implying that there are directional
asymmetries (convergent versus divergent eye movements) in the slow fusional
component of vergence. Data suggest that a potential interaction between the
version system and the slow fusional vergence system may exist. Results have
clinical relevance because patients with convergence or divergence
insufficiency/excess may potentially show more pronounced differences between
symmetrical and asymmetrical phoria adaptation compared to binocularly normal
controls. These differences might also be relevant to clinical measurements such
as vergence fusional range, which can be measured symmetrically (with Risley
prisms in a phoroptor) or asymmetrically (with prism bar).
PMID- 29940193
TI - Examining neural correlates of psychopathology using a lesion-based approach.
AB - Studies of individuals with focal brain damage have long been used to expand
understanding of the neural basis of psychopathology. However, most previous
studies were conducted using small sample sizes and relatively coarse methods for
measuring psychopathology or mapping brain-behavior relationships. Here, we
examined the factor structure and neural correlates of psychopathology in 232
individuals with focal brain damage, using their responses to the Minnesota
Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Factor
analysis and voxel-based lesion symptom mapping were used to examine the
structure and neural correlates of psychopathology in this sample. Consistent
with existing MMPI-2-RF literature, separate internalizing, externalizing, and
psychotic symptom dimensions were found. In addition, a somatic dimension likely
reflecting neurological symptoms was identified. Damage to the medial temporal
lobe, including the hippocampus, was associated with scales related to both
internalizing problems and psychoticism. Damage to the medial temporal lobe and
orbitofrontal cortex was associated with both a general distrust of others and
beliefs that one is being personally targeted by others. These findings provide
evidence for the critical role of dysfunction in specific frontal and temporal
regions in the development of psychopathology.
PMID- 29940195
TI - Metapopulation model using commuting flow for national spread of the 2009 H1N1
influenza virus in the Republic of Korea.
AB - We study the spatial-temporal pattern of the spread of the 2009 H1N1 influenza
virus using a metapopulation model linked by commuting flow based on the reported
influenza cases during the early stages of the epidemic in the Republic of Korea.
The spatial heterogeneities, such as the local reproductive number and peak time,
are investigated at province level. Furthermore, we discuss the effect of early
intervention strategies, isolation and commuting restrictions, on the reduction
of incidence at each province level. A major finding of this study is that early
intervention at the source area of infection is more effective than interventions
at the commuting-hub areas if the cost is limited.
PMID- 29940194
TI - Balancing body ownership: Visual capture of proprioception and affectivity during
vestibular stimulation.
AB - The experience of our body as our own (i.e. body ownership) involves integrating
different sensory signals according to their contextual relevance (i.e.
multisensory integration). Until recently, most studies of multisensory
integration and body ownership concerned only vision, touch and proprioception;
the role of other modalities, such as the vestibular system and interoception,
has been neglected and remains poorly understood. In particular, no study to date
has directly explored the combined effect of vestibular and interoceptive signals
on body ownership. Here, we investigated for the first time how Galvanic
Vestibular Stimulation (left, right, sham), tactile affectivity (a reclassified
interoceptive modality manipulated by applying touch at C-tactile optimal versus
non-optimal velocities), and their combination, influence proprioceptive and
subjective measures of body ownership during a rubber hand illusion paradigm with
healthy participants (N = 26). Our results show that vestibular stimulation (left
GVS) significantly increased proprioceptive drift towards the rubber hand during
mere visual exposure to the rubber hand. Moreover, it also enhanced participants'
proprioceptive drift towards the rubber hand during manipulations of
synchronicity and affective touch. These findings suggest that the vestibular
system influences multisensory integration, possibly by re-weighting both the two
way relationship between proprioception and vision, as well as the three-way
relationship between proprioception, vision and affective touch. We discuss these
findings in relation to current predictive coding models of multisensory
integration and body ownership.
PMID- 29940196
TI - Viral interference between low pathogenic avian influenza H9N2 and avian
infectious bronchitis viruses in vitro and in ovo.
AB - BACKGROUND: Low pathogenic avian influenza (LPAI) H9N2 and infectious bronchitis
virus (IBV) are important pathogens of poultry, causing important economic losses
for the sector. Replication interference between these two viruses was described
using cell cultures (CC) and embryonated chicken eggs (ECE). Chicken embryo lung
(CEL) and ECE were simultaneously or sequentially infected with IBV vaccine
strain (H120) and LPAIV-H9N2 (A/Ck/TUN/145/2012) to evaluate viral interactionsin
vitro and in ovo, respectively. Real-time RT-PCR was developed to specifically
quantify both AIV and IBV genomes as well as viral gene copy numbers during mixed
infections. The amount of IL-1 beta, in supernatants of co-infected cell
cultures, was determined using an ELISA assay. RESULTS: Quantitative results of
AIV and IBV co-infection showed that interferences between the two viruses
yielded decreased viral growth. However, in the case of super-infection, the
second virus, either AIV or IBV, induced a decrease in the growth of the first
inoculated virus. CONCLUSION: It appears that either AIV or IBV has a negative
impact on the other virus growth when they are inoculated simultaneously or
sequentially. The ELISA results showed that higher level of secreted IL-1beta
varies, depending on the viral interference conditions between both viruses,
during mixed infections.
PMID- 29940197
TI - Novel short isoforms of adenylyl cyclase as negative regulators of cAMP
production.
AB - Here, we cloned a new family of four adenylyl cyclase (AC) splice variants from
interleukin-1beta (IL-1beta)-transdifferentiated vascular smooth muscle cells
(VSMCs) encoding short forms of AC8 that we have named "AC8E-H". Using biosensor
imaging and biochemical approaches, we showed that AC8E-H isoforms have no
cyclase activity and act as dominant-negative regulators by forming heterodimers
with other full-length ACs, impeding the traffic of functional units towards the
plasma membrane. The existence of these dominant-negative isoforms may account
for an unsuspected additional degree of cAMP signaling regulation. It also
reconciles the induction of an AC in transdifferentiated VSMCs with the
vasoprotective influence of cAMP. The generation of alternative splice variants
of ACs may constitute a generalized strategy of adaptation to the cell's
environment whose scope had so far been ignored in physiological and/or
pathological contexts.
PMID- 29940198
TI - Exercise preconditioning and low dose copper nanoparticles exhibits
cardioprotection through targeting GSK-3beta phosphorylation in
ischemia/reperfusion induced myocardial infarction.
AB - BACKGROUND: Drinking water from copper vessels and aerobic exercise have been the
known facts for cardioprotection. Our previous report explored the significant
cardioprotective potential of copper and exercise training by increasing
phosphorylation of GSK-3beta and anti-oxidant potential. OBJECTIVE: Present study
focuses the therapeutic potential of CuNP and exercise training through their
molecular interaction with GSK-3beta, inflammatory cytokinin, oxidative stress
and necrosis. METHODS: The Myocardial damage was assessed by estimating the serum
nitrite/nitrate concentration, increased CKMB, LDH, cTnI level, oxidative stress,
inflammatory cytokinin and structural abnormalities in I/R insulted rats.
Expression of Akt/pAkt and GSK-3beta/pGSK-3beta was measured by western blotting.
RESULT: Treatment with CuNP (1 mg/kg/day, p.o., 4 weeks) and exercise training
(swimming, 90 min/4 weeks) either alone or in combination markedly reduced I/R
induced myocardial damage by attenuating biochemical and structural alteration. A
significant reduction in oxidative stress and inflammatory mediators were
observed in CuNP and exercise training treatment against I/R insulted rats.
Moreover, improved serum NO bioavailability was observed in CuNP and exercise
treated rats. Wortmannin associated blockage of cardioprotection induced by CuNP
and exercise training and up-regulation of pAkt and pGSK-3beta in I/R insulted
heart confirmed the GSK-3beta phosphorylation potential of CuNP and exercise
training and -associated cardioprotection. CONCLUSION: Treatment with CuNP and
exercise training either alone or in combination favourably phosphorylate GSK
3beta kinase pathways and further diminish oxidative stress, inflammatory
cytokines, apoptosis and increase serum bioavailability of NO in the I/R insulted
rats which tends to protect myocardial damage.
PMID- 29940199
TI - Quantification characteristics of digital spiral analysis for understanding the
relationship among tremor and clinical measures in persons with multiple
sclerosis.
AB - BACKGROUND: Multiple sclerosis (MS) is a degenerative neurological condition
causing demyelination and neuronal loss. Tremor, a symptom of MS, is prevalent in
45.0-46.8% NARCOMS registrants. Although several tools to measure tremor exist,
few outcomes are quantitative or regularly utilized clinically. NEW METHOD:
Introduction of a novel adaptation of the digital spiral drawing to find a quick,
sensitive, and clinically useful technique, to predict tremor in persons with MS
(pwMS). Digital spiral measures included: Segment Rate (SEGRT), Standard
Deviation (SD) of Radial Velocity (VSD-R), SD of Tangential Velocity (VSD-T), SD
of Overall Velocity (VSD-O), Mean Drawing Velocity (MNV-O) and Mean Pen Pressure
Acceleration (MNA-P). Digital spiral measures were compared with the manual
Archimedes Spiral (AS) drawing and the following clinical measures: Finger-Nose
Test (FNT), presence of visually observed intention tremor (VOT), Nine-Hole Peg
Test (NHPT), and Box and Block Test (BBT). RESULTS: All clinical measures
utilized demonstrated significant relationships with all digital variables,
except VSD-R. The forward-stepwise regression revealed BBT accounted for the most
variance, followed by SEGRT. Comparison with Existing Methods: SEGRT is more
sensitive in detecting VOT and better for quantifying tremor than AS. BBT and
SEGRT are optimal predictive measures for tremor. CONCLUSIONS: SEGRT has stronger
sensitivity and negative predictive value than AS in detecting VOT. All clinical
measures (NHPT, FNT, BBT, and AS) were significantly associated with the digital
variables (SEGRT, VSD-T, VSD-O, MNV-O, and MNA-P) except for VSD-R. After
controlling for Patient Determined Disease Steps (PDDS), BBT and SEGRT are the
best predictive measures for tremor.
PMID- 29940200
TI - Hypomethylation of mitochondrial D-loop and ND6 with increased mitochondrial DNA
copy number in the arsenic-exposed population.
AB - Groundwater arsenic contamination has become a serious global concern due to its
adverse effects on human health. Arsenic-induced reactive oxygen species trigger
oxidative stress inside mitochondria, which initiate a cascade of events
including altered mitochondrial (mt) membrane potential, uncoupling of electron
transport chain, and mtDNA damage. A case-control study was conducted to examine
the association between arsenic exposure and differences in mtDNA methylation and
to assess the downstream consequences. We recruited 221 arsenic-exposed
individuals, including 106 individuals with skin lesions (WSL) and 115 subjects
without any skin lesions (WOSL) from the Murshidabad district, West Bengal,
India. The unexposed group included 101 individuals from the arsenic unexposed
area in East Midnapore. We analyzed the status of mtDNA methylation in D-loop
region and ND6 gene by methylation-specific PCR. Gene expression was studied by
quantitative real-time PCR. Significant hypomethylation in both D-loop and ND6
was observed with a consequent increase in their target gene expression and
higher mtDNA copy number in arsenic-exposed populations compared to controls.
Further mechanistic insights regarding mitochondrial epigenetic alteration in
arsenic exposure will be of critical importance for the prevention of adverse
health effects.
PMID- 29940201
TI - Epigallocatechin gallate improves insulin resistance in HepG2 cells through
alleviating inflammation and lipotoxicity.
AB - AIMS: High levels of circulating free fatty acids (FFAs), inflammation and
oxidative stress are important causes for insulin resistance (IR) and type 2
diabetes mellitus. The aim of this study was to investigate the mechanisms of
EGCG in alleviating IR in HepG2 cells. METHODS: HepG2 cells were treated with 25
mM glucose, 0.25 mM palmitic acid (PA), or 50 MUM EGCG for 24 h. RESULTS: EGCG
increased glucose uptake and decreased glucose content. EGCG markedly decreased
the levels of inflammatory and oxidative stress factors including nuclear factor
kappaB (NF-kappaB), tumor necrosis factor-alpha, interleukin-6, reactive oxygen
species, malondialdehyde and p53 protein, and markedly increased superoxide
dismutases (SOD), glutathione peroxidase and SOD2 protein. EGCG significantly
downregulated the levels of FFAs, triacylglycerol and cholesterol in HepG2 cells.
The glucose transporter 2 (GLUT2) protein and its downstream proteins peroxisome
proliferator-activated receptor gamma coactivator (PGC)-1beta were significantly
increased, and sterol regulatory element-binding-1c (SREBP-1c) protein, and fatty
acid synthase (FAS) were significantly decreased by EGCG in HepG2. Moreover, the
foregoing effects were reversed by siRNA-mediated knockdown of GLUT2. CONCLUSION:
Our data demonstrated that EGCG improved IR, possibly through ameliorating
glucose (25 mM) and PA (0.25 mM)-induced inflammation, oxidative stress, and FFAs
via the GLUT2/PGC-1beta/SREBP-1c/FAS pathway in HepG2 cells.
PMID- 29940202
TI - Why aren't you stopping now?!' Exploring accounts of white women breastfeeding
beyond six months in the East of England.
AB - Breastfeeding infants for a period of two years is endorsed by international
health agencies such as the World Health Organisation. However, discourses of
breastfeeding in a British context are complex and contradictory, juxtaposing
representations of breastfeeding as healthy and a moral obligation for mothers
with views of the act as unseemly and an expectation that nursing women practice
'socially sensitive lactation' especially in public spaces. Sustained
breastfeeding rates in the UK are poor and most British women discontinue
breastfeeding well before six months. Mothers who elect to feed their infants at
the breast for longer than these normative periods appear to experience suspicion
and disapproval, especially in a public context and breastfeeding women are only
legally protected in feeding their infants in public for up to six months.
Although breastfeeding research is flourishing, research on this particular
population of mothers remains relatively limited. Therefore, in this study, we
explore in-depth experiential accounts of eight women, resident in a town in the
East of England, who breastfed their infants beyond six months. Using
interpretative phenomenological analysis four themes are presented. Really
horrible looks': stigma from families and the community', 'Feeling quite
exposed': managing extended breastfeeding etiquette', 'Weird freaky paedophiles':
representations of extended breastfeeding women in the media' and 'You really
need that': the importance of support for longer-term breastfeeding women'.
Applications to extended breastfeeding promotion and advocacy are discussed.
PMID- 29940203
TI - Toluene diisocyanate exposure and autotaxin-lysophosphatidic acid signalling.
AB - Toluene diisocyanate (TDI) is a reactive chemical used in manufacturing plastics.
TDI exposure adversely affects workers' health, causing occupational asthma, but
individuals differ in susceptibility. We recently suggested a role for signalling
mediated by the enzyme autotaxin (ATX) and its product, lysophosphatidic acid
(LPA), in TDI toxicity. Here we genotyped 118 TDI-exposed workers for six single
nucleotide polymorphisms (SNPs) in genes encoding proteins implicated in ATX-LPA
signalling: purinergic receptor P2X7 (P2RX7), CC motif chemokine ligand 2 (CCL2),
interleukin 1beta (IL1B), and caveolin 1 (CAV1). Two P2RX7 SNPs (rs208294 and
rs2230911) significantly modified the associations between a biomarker of TDI
exposure (urinary 2,4-toluene diamine) and plasma LPA; two IL1B SNPs (rs16944 and
rs1143634) did not. CAV1 rs3807989 modified the associations, but the effect was
not statistically significant (p = 0.05-0.09). In vitro, TDI-exposed bronchial
epithelial cells (16HBE14o-) rapidly released ATX and IL-1beta. P2X7 inhibitors
attenuated both responses, but confocal microscopy showed non-overlapping
localizations of ATX and IL-1beta, and down-regulation of CAV1 inhibited the ATX
response but not the IL-1beta response. This study indicates that P2X7 is pivotal
for TDI-induced ATX-LPA signalling, which was modified by genetic variation in
P2RX7. Furthermore, our data suggest that the TDI-induced ATX and IL-1beta
responses occur independently.
PMID- 29940204
TI - Saccharides, oligosaccharides, and polysaccharides nanoparticles for biomedical
applications.
AB - Modern requirements for designing efficient nanocarriers against diseases such as
cancer are very complex. A suitable nanocarrier should indeed remain colloidally
stable in the body, be biodegradable, target specific tumor cells, and release
efficiently drugs. These challenging tasks can be overcome by using the chemistry
of saccharides and polysaccharides. We discuss here recent applications of
carbohydrates-based materials for providing biodegradability, enhancing contrast
in bioimaging, a stealth effect for controlling the composition of protein
corona, and targeting ability.
PMID- 29940205
TI - Aggravation of mild axillary hidradenitis suppurativa by microwave ablation:
results of a randomized intra-patient controlled trial.
PMID- 29940206
TI - Serotonergic mechanisms involved in antidepressant-like responses evoked by GLT-1
blockade in rat infralimbic cortex.
AB - Novel fast-acting antidepressant strategies, such as ketamine and deep brain
stimulation, enhance glutamatergic neurotransmission in medial prefrontal cortex
(mPFC) regions via AMPA receptor (AMPA-R) activation. We recently reported that
the regionally-selective blockade of the glial glutamate transporter-1 (GLT-1) by
dihydrokainic acid (DHK) microinfusion in rat infralimbic cortex (IL), the most
ventral part of the mPFC, evoked immediate (10 min) antidepressant-like
responses, which involved AMPA-R activation and were associated to increased
serotonin (5-hydroxytryptamine, 5-HT) release. Given the reciprocal connectivity
between the mPFC and the serotonergic dorsal raphe nucleus (DR), here we examined
the serotoninergic mechanisms involved in the reported antidepressant-like
responses of DHK microinfusion. First, we show that antidepressant-like responses
evoked by IL application of DHK and citalopram are mediated by local 5-HT1A
receptors (5-HT1A-R), since they are cancelled by previous IL WAY100635
microinfusion. Second, IL DHK microinfusion increases excitatory inputs onto DR,
as shown by an increased glutamate and 5-HT release in DR and by a selective
increase of c-Fos expression in DR 5-HT neurons, not occurring in putative
GABAergic neurons. This view is also supported by an increased 5-HT release in
ventral hippocampus following IL DHK microinfusion. Interestingly, antidepressant
like responses evoked by IL DHK lasted for 2 h and could be prolonged for up to
24 h by attenuating self-inhibitory effects via 5-HT1A autoreceptors. In
contrast, the antidepressant-like effects of S-AMPA microinfusion in IL were
short-lasting. Together, our results further support a prominent role of the IL
DR pathway and of ascending 5-HT pathways in mediating antidepressant-like
responses evoked by glutamatergic mechanisms.
PMID- 29940207
TI - Attenuated dopaminergic neurodegeneration and motor dysfunction in
hemiparkinsonian mice lacking the alpha5 nicotinic acetylcholine receptor
subunit.
AB - Preclinical studies suggest the involvement of various subtypes of nicotinic
acetylcholine receptors in the pathophysiology of Parkinson's disease, a
neurodegenerative disorder characterized by the death of dopaminergic neurons in
the substantia nigra pars compacta (SNC). We studied for the first time the
effects of alpha5 nicotinic receptor subunit gene deletion on motor behavior and
neurodegeneration in mouse models of Parkinson's disease and levodopa-induced
dyskinesia. Unilateral dopaminergic lesions were induced in wild-type and alpha5
KO mice by 6-hydroxydopamine injections into the striatum or the medial forebrain
bundle. Subsequently, rotational behavior induced by dopaminergic drugs was
measured. A subset of animals received chronic treatments with levodopa and
nicotine to assess levodopa-induced dyskinesia and antidyskinetic effects by
nicotine. SNC lesion extent was assessed with tyrosine hydroxylase
immunohistochemistry and stereological cell counting. Effects of alpha5 gene
deletion on the dopaminergic system were investigated by measuring ex vivo
striatal dopamine transporter function and protein expression, dopamine and
metabolite tissue concentrations and dopamine receptor mRNA expression.
Hemiparkinsonian alpha5-KO mice exhibited attenuated rotational behavior after
amphetamine injection and attenuated levodopa-induced dyskinesia. In the
intrastriatal lesion model, dopaminergic cell loss in the medial cluster of the
SNC was less severe in alpha5-KO mice. Decreased striatal dopamine uptake in
alpha5-KO animals suggested reduced dopamine transporter function as a mechanism
of attenuated neurotoxicity. Nicotine reduced dyskinesia severity in wild-type
but not alpha5-KO mice. The attenuated dopaminergic neurodegeneration and motor
dysfunction observed in hemiparkinsonian alpha5-KO mice suggests potential for
alpha5 subunit-containing nicotinic receptors as a novel target in the treatment
of Parkinson's disease.
PMID- 29940208
TI - Inhibition of non-NMDA ionotropic glutamate receptors delays the retinal
degeneration in rd10 mouse.
AB - Retinitis pigmentosa (RP) is a hereditary blinding disease characterized by
neurodegeneration of photoreceptors. Retinal ganglion cells (RGCs) in animal
models of RP exhibit an abnormally high spontaneous activity that interferes with
signal processing. Blocking AMPA/Kainate receptors by bath application of CNQX
decreases the spontaneous firing, suggesting that inhibiting these receptors in
vivo may help maintain the function of inner retinal neurons in rd10 mice
experiencing photoreceptor degeneration. To test this, rd10 mice were i.p.
injected with CNQX or GYKI 52466 (an AMPA receptor antagonist) for 1-2 weeks, and
examined for their retinal morphology (by immunocytochemistry), function (by MEA
recordings) and visual behaviors (using a black/white box). Our data show that
iGluRs were up-regulated in the inner plexiform layer (IPL) of rd10 retinas.
Application of CNQX at low doses both in vitro and in vivo, attenuated the
abnormal spontaneous spiking in RGCs, and increased the light-evoked response of
ON RGCs, whereas GYKI 52466 had little effect. CNQX application also improved the
behavioral performance. Interestingly, in vivo administration of CNQX delayed
photoreceptor degeneration, evidenced by the increased cell number and restored
structure. CNQX also improved the structure of bipolar cells. Together, we
demonstrated that during photoreceptor degeneration, blockade of the non-NMDA
iGluRs decelerates the progression of RGCs dysfunction, possibly by dual
mechanisms including slowing photoreceptor degeneration and modulating signal
processing within the IPL. Accordingly, this strategy may effectively extend the
time window for treating RP.
PMID- 29940210
TI - Escaping Sonder.
PMID- 29940209
TI - Improving a Full Range of Advance Care Planning Behavior Change and Action
Domains: The PREPARE Randomized Trial.
AB - CONTEXT: Advance care planning (ACP) engagement includes a wide range of
behaviors and actions related to discussions and documentation, yet few ACP
intervention studies measure the full process. OBJECTIVES: The objective of the
study was to compare the effects of an easy-to-read advance directive (AD) versus
an ACP web site plus the AD (PREPARE + AD) on Behavior Change Processes and
Actions, including discussions and documentation. METHODS: Secondary data were
from a completed ACP trial. Participants were primary care patients, >=60 years
old, with two comorbidities. We used the validated ACP Engagement Survey to
examine six-month change in subscales measuring Behavior Change Processes
(knowledge, contemplation, self-efficacy, readiness) and Actions (decision
makers, quality of life, flexibility for decision makers, asking clinicians
questions), specifically related to discussions and documentation. We used
adjusted mixed-effects linear models to compare mean change and engagement over
time. RESULTS: Compared to the AD-only, PREPARE + AD resulted in greater
increases in all Behavior Change Processes subscales and Actions related to
decision makers, quality of life, and flexibility (all P-values <=0.005). Both
interventions significantly increased the proportion of participants who engaged
in ACP discussions (PREPARE + AD, 99.5%; AD-only, 93.3%) and documentation
(PREPARE + AD, 99.5%; AD-only, 90.4%), with greater increases for PREPARE + AD
(all P-values <0.001). CONCLUSION: Both PREPARE plus an easy-to-read AD and an AD
only markedly increased ACP engagement in a full range of ACP behaviors,
including discussions and documentation, and engagement was nearly 100% with
PREPARE + AD. Future ACP studies should examine a full range of ACP behaviors
beyond ADs and the impact of PREPARE and easy-to-read AD implementation on health
care systems.
PMID- 29940211
TI - The food safety of DP-356O43 soybeans on SD rats reflected by physiological
variables and fecal microbiota during a 90-day feeding study.
AB - Soybean is an important food resource for the eastern countries and herbicide
tolerant genetically modified soybeans (GMS) were widely developed to deal with
weeds problems. Unprocessed soybean flour instead of dehulled and defatted
soybean meal was used to reflect the safety of soybean food in whole. Rats were
given formulated diets containing DP-356O43 or non-GM soybean JACK at an
incorporation rate of 7.5%, 15%, or 30% (w/w), respectively for 90 days. Targeted
traditional toxicological response variables were measured to reflect the
holistic health of animals. No treatment-related adverse or toxic effects were
observed based on an examination of the daily clinical signs, body weight, food
consumption, hematology, serum biochemistry, and organ weight or based on gross
and histopathological examination. The results demonstrate that the soybean DP
356O43 is as safe for consumption as conventional soybean JACK. In the current
study, the effect of a herbicide-tolerant GMS DP-356043 on identified intestinal
microbiota was evaluated in a rodent feeding study compared with its conventional
control JACK. Feces samples from rats consuming different diets were collected
before the start of the experiment (time 0) and at monthly intervals (at the end
of the 1st, 2nd and 3rd months) over the course of 90 days. Six types of
bacterias shared by humans and rats were detected with Q-PCR. The results of QPCR
indicated that the GMS 356O43 had a comparable effect on the abundance of
Bifidobacterium group, Clostridium perfringens subgroup, Escherichia coli, and
Bacteroides-Prevotella group as the non-GMS JACK.
PMID- 29940212
TI - Fragrance allergens in household detergents.
AB - Consumers are confronted with a large number of fragrance allergens from various
sources. Until now, the discussion of exposure sources has mainly addressed
cosmetic products and neglected other scented products in households. For the
first time, fragrance allergens were evaluated in a complete set of detergents in
households. In 131 households, we investigated the prevalence of detergents and
searched their lists of ingredients for 26 fragrance allergens liable to be
indicated on products according to the European Detergents Regulations. On the
ingredient lists of 1447 products, these 26 fragrance substances were named
almost 2000 times, most often limonene, linalool and hexyl cinnamal. Benzyl
salicylate was used frequently in all-purpose cleaners. Linalool and limonene,
hexyl cinnamal and butylphenyl methylpropional and citronellol and linalool co
occurred most often together in products. Fragrance allergens co-occurring
together most frequently within households were eugenol, coumarin and cinnamyl
alcohol. The study shows that detergents could play a relevant role for the
exposure of consumers towards fragrance allergens and that they should not be
underestimated as an exposure source during the exposure assessment.
PMID- 29940213
TI - Semaphorin 3A as an inhibitive factor for migration of olfactory ensheathing
cells through cofilin activation is involved in formation of olfactory nerve
layer.
AB - Olfactory ensheathing cells (OECs) migrate from olfactory epithelium towards
olfactory bulb (OB), contributing to formation of the presumptive olfactory nerve
layer during development. However, it remains unclear that molecular mechanism of
regulation of OEC migration in OB. In the present study, we found that OECs
highly expressed the receptors of semaphorin 3A (Sema3A) in vitro and in vivo,
whereas Sema3A displayed a gradient expression pattern with higher in inner layer
of OB and lower in outer layer of OB. Furthermore, the collapse assays, Boyden
chamber migration assays and single-cell migration assays showed that Sema3A
induced the collapse of leading front of OECs and inhibited OEC migration.
Thirdly, the leading front of OECs exhibited adaptation in a protein synthesis
independent manner, and endocytosis-dependent manner during Sema3A-induced OEC
migration. Finally, Sema3A-induced collapse of leading front was required the
decrease of focal adhesion and a retrograde F-actin flow in a cofilin activation
dependent manner. Taken together, these results demonstrate that Sema3A as an
inhibitive migratory factor for OEC migration through cofilin activation is
involved in the formation of olfactory nerve layer.
PMID- 29940214
TI - Genistein inhibits African swine fever virus replication in vitro by disrupting
viral DNA synthesis.
AB - African swine fever virus (ASFV) is the causal agent of a highly-contagious and
fatal disease of domestic pigs, leading to serious socio-economic consequences in
affected countries. Once, neither an anti-viral drug nor an effective vaccines
are available, studies on new anti-ASFV molecules are urgently need. Recently, it
has been shown that ASFV type II topoisomerase (ASFV-topo II) is inhibited by
several fluoroquinolones (bacterial DNA topoisomerase inhibitors), raising the
idea that this viral enzyme can be a potential target for drug development
against ASFV. Here, we report that genistein hampers ASFV infection at non
cytotoxic concentrations in Vero cells and porcine macrophages. Interestingly,
the antiviral activity of this isoflavone, previously described as a topo II
poison in eukaryotes, is maximal when it is added to cells at middle-phase of
infection (8 hpi), disrupting viral DNA replication, blocking the transcription
of late viral genes as well as the synthesis of late viral proteins, reducing
viral progeny. Further, the single cell electrophoresis analysis revealed the
presence of fragmented ASFV genomes in cells exposed to genistein, suggesting
that this molecule also acts as an ASFV-topo II poison and not as a reversible
inhibitor. No antiviral effects were detected when genistein was added before or
at entry phase of ASFV infection. Molecular docking studies demonstrated that
genistein may interact with four residues of the ATP-binding site of ASFV-topo II
(Asn-144, Val-146, Gly-147 and Leu-148), showing more binding affinity (-4.62
kcal/mol) than ATP4- (-3.02 kcal/mol), emphasizing the idea that this viral
enzyme has an essential role during viral genome replication and can be a good
target for drug development against ASFV.
PMID- 29940215
TI - Season, weather and predictors of healthcare-associated Gram-negative bloodstream
infections: a case-only study.
AB - BACKGROUND: Recent studies reported seasonality in healthcare-associated
infections (HCAI). The association of this phenomenon with other risk factors for
HCAI is not clear. AIM: To analyse the interplay of season, weather and usual
predictors of healthcare-associated bloodstream infections caused by Gram
negative bacilli (GNB-BSI). METHODS: A case-only study was conducted in a
teaching hospital in Brazil. The study enrolled 446 subjects with GNB-BSI
diagnosed from July 2012 to June 2016. Demographic data, comorbidities, invasive
procedures and use of antimicrobials were reviewed in medical charts. The season
in which GNB-BSI occurred, and weather parameters on the day of diagnosis were
recorded. Factors associated with occurrence of GNB-BSI in different seasons
(reference category: winter) and caused by different GNB (reference category:
Escherichia coli) were analysed. Uni- and multi-variable models of multi-nomial
logistic regression were used for analysis. FINDINGS: GNB-BSI diagnosed in summer
was more likely to be caused by Klebsiella spp. [odds ratio (OR) 5.33; 95%
confidence interval (CI) 2.04-13.96] or Acinetobacter baumannii (OR 2.69; 95% CI
1.04-6.96), and there was an association between Klebsiella spp. and spring (OR
2.86; 95% CI 1.14-7.18). Average temperature on the day of diagnosis was
associated with Klebsiella spp. (OR 1.19; 95% CI 1.07-1.33) and A. baumannii (OR
1.20; 95% CI 1.07-1.34). CONCLUSION: Warm seasons and daily temperature impact on
the aetiology of GNB-BSI, even in models adjusted for usual risk factors. One
possible explanation for these findings is that seasonality of healthcare
associated pathogens is intrinsic to micro-organisms, and not associated with
comorbidities, procedures or use of antimicrobials.
PMID- 29940216
TI - Exposure to Acute and Chronic Fluoxetine has Differential Effects on Sociability
and Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus of Juvenile Male
BALB/c Mice.
AB - Although the neurobiological mechanisms underlying autism spectrum disorder (ASD)
are still unknown, dysregulation of serotonergic systems has been implicated in
the etiology of ASD, and serotonergic antidepressant drugs are often prescribed
to treat some symptoms of ASD. The BALB/c strain of mice express a dysregulated
serotonergic system and a phenotype that is relevant to ASD. In this study,
juvenile male BALB/c mice were exposed to the selective serotonin reuptake
inhibitor fluoxetine either chronically (18 mg/kg/day in drinking water, post
natal day (PND) 28-39) or acutely (18 mg/kg, i.p.; PND40), or to vehicle control
conditions (0.9% sterile saline, i.p.; PND40), prior to being exposed to the
three-chambered sociability test (SAT; PND40). One cohort of mice then received
an injection of the aromatic amino acid decarboxylase inhibitor, NSD-1015, and
one hour later brain tissue was collected for quantification of 5
hydroxytryptophan accumulation in the dorsal raphe nucleus (DR) as a measure of
TPH2 activity. For the second cohort, brain tissue was collected ninety minutes
after the onset of the social phase of the SAT and prepared for
immunohistochemical staining for c-Fos and TPH2 to measure the activation of
serotonergic neurons within subregions of the DR. Acute fluoxetine decreased
social behavior, while chronic fluoxetine increased social behavior compared with
vehicle-treated controls. Furthermore, acute and chronic fluoxetine treatments
were without effect on TPH2 activity but differentially affected populations of
serotonergic neurons in the DR. These data are consistent with the hypothesis
that serotonergic systems are implicated in social behavior that is relevant for
ASD.
PMID- 29940217
TI - Pharmacokinetic and pharmaceutical properties of a novel buprenorphine/naloxone
sublingual tablet for opioid substitution therapy versus conventional
buprenorphine/naloxone sublingual tablet in healthy volunteers.
AB - PURPOSE: A novel sublingual buprenorphine/naloxone rapidly-dissolving tablet (BNX
RDT) for opioid substitution therapy has been developed for improved
bioavailability, rapid disintegration and improved taste masking. We compared the
bioavailability and pharmaceutical properties of BNX-RDT with conventional
buprenorphine/naloxone sublingual tablets (BNX). METHODS: Fasting, open-label,
randomized, single-dose, two-cohort crossover study in healthy volunteers under
naltrexone block. Cohort 1 (high-dose, N = 64) received BNX-RDT 11.4/2.9 mg and
BNX 16/4 mg. Cohort 2 (low-dose, N = 61) received BNX-RDT 2.9/0.71 mg and BNX 4/1
mg. Plasma samples were collected over 72 h. Relative systemic exposures of
buprenorphine and naloxone were assessed using standard statistical models for
bioequivalence analysis. Pharmaceutical assessments included dissolve time, taste
and mouthfeel assessments, and overall preference. RESULTS: BNX-RDT 11.4/2.9 mg
provided equivalent buprenorphine and naloxone exposure to BNX 16/4 mg. BNX-RDT
2.9/0.71 mg provided ~20% lower buprenorphine and 35% lower naloxone exposure
compared with BNX 4/1 mg. The comparison of BNX-RDT 2.9/0.71 mg with BNX 4/1 mg
did not fully meet equivalence criteria. BNX-RDT was associated with improved
dose proportionality across strengths compared with BNX (post hoc analysis),
resulting in lower exposure from BNX-RDT relative to BNX at the lower strength.
Median perceived dissolve times were significantly shorter for BNX-RDT than BNX
at high (8.5 versus 16.2 min) and low (7.6 versus 9.1 min) doses. Taste and
mouthfeel were rated significantly more pleasant than BNX, with ~78% of subjects
preferring BNX-RDT. CONCLUSION: BNX-RDT provided improved buprenorphine
absorption compared to a conventional sublingual tablet, with shorter dissolve
times and improved taste and mouthfeel, resulting in a high preference for the
novel formulation.
PMID- 29940219
TI - Circulating tumor DNA in blood: Future genomic biomarkers for cancer detection.
AB - Cancer is characterized by Darwinian evolution and is a primary cause of
mortality and morbidity around the globe. Over the preceding decade, the
treatment of cancer has been markedly improved by many targeted therapies, but
these treatments have given birth to new challenges and issues. Clonal evolution
and tumor heterogeneity present a significant challenge in designing cancer
therapies. Fortunately, these restrictions have been overcome by technological
advancements allowing us to track both genetic and epigenetic aberrations. Cell
free circulating tumor DNA (ctDNA) analysis, or "liquid biopsy" from a blood
sample, provides the opportunity to track the genetic landscape of cancerous
lesions. This review focuses on ctDNA analysis as a noninvasive method and
versatile biomarker for cancer treatment and technological advancements for ctDNA
analysis. This method may able to cope with all the challenges associated with
previous cancer therapies and has the potential to monitor minimal residual
disease, tumor burden, and therapy response and provide rapid detection of
relapse. However, there are many challenges that still need to be addressed.
Future prognosis, diagnosis, and analysis of ctDNA require reproducibility and
accuracy of results, which are not possible without the validation and
optimization of procedures. Integrated digital error suppression has thus far
shown promise in the detection of ctDNA in cancer.
PMID- 29940218
TI - Cross - site comparison of excitation-contraction coupling using impedance and
field potential recordings in hiPSC cardiomyocytes.
AB - INTRODUCTION: Since 2005 the S7B and E14 guidances from ICH and FDA have been in
place to assess a potential drug candidate's ability to cause long QT syndrome.
To refine these guidelines, the FDA proposed the Comprehensive in vitro
Proarrhythmia Assay (CiPA) initiative, where the assessment of drug effects on
cardiac repolarization was one subject of investigation. Within the myocyte
validation study, effects of pharmaceutical compounds on human induced
pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were assessed and this
article will focus on the evaluation of the proarrhythmic potential of 23 blinded
drugs in four hiPSC-CM cell lines. METHODS: Experiments were performed on the
CardioExcyte 96 at different sites. A combined readout of contractility (via
impedance) and electrophysiology endpoints (field potentials) was performed.
RESULTS: Our data demonstrates that hERG blockers such as dofetilide and further
high risk categorized compounds prolong the field potential duration. Arrhythmia
were detected in both impedance as well as field potential recordings.
Intermediate risk compounds induced arrhythmia in almost all cases at the highest
dose. In the case of low risk compounds, either a decrease in FPDmax was
observed, or not a significant change from pre-addition control values.
DISCUSSION: With exceptions, hiPSC-CMs are sensitive and exhibit at least 10%
delayed or shortened repolarization from pre-addition values and arrhythmia after
drug application and thus can provide predictive cardiac electrophysiology data.
The baseline electrophysiological parameters vary between iPS cells from
different sources, therefore positive and negative control recordings are
recommended.
PMID- 29940220
TI - The importance of left heart disease as a cause of pulmonary hypertension in
COPD.
AB - Chronic obstructive pulmonary disease (COPD) is a common respiratory condition
that presents with varying degrees of severity and can be complicated by further
comorbidities. Up to a third can also have pulmonary hypertension, which is an
important risk factor associated with an increase in morbidity and mortality. The
etiology of pulmonary hypertension contributes to diagnosis. Considering and
identifying the type of pulmonary hypertension at the right time will influence
management and outcome in patients with COPD.
PMID- 29940221
TI - Targeting mitochondrial calcium transport in myocardial infarction.
PMID- 29940222
TI - The landscape of acute pericarditis in Greece: Experience from a tertiary
referral center.
PMID- 29940223
TI - Do we need biomarkers for diabetics progressing to heart failure?
AB - Cardiovascular changes produce unfavorable outcomes including arterial
hypertension and diabetes, which are related to the increased risk of heart
failure (HF). The latter is highly prevalent in the setting of glucose metabolism
dysregulation and high hemodynamic load, and identifying predictors of the
incidence of HF with preserved ejection fraction (HFpEF) requires a research and
is a clinical need. Toward this end, the variability in glucose regulation
represents a novel dynamic way to comprehend and study the impact of glycemia.
The results of the published study highlight the independent association of
glycated hemoglobin A1c variability with the development of HFpEF in hypertensive
diabetic patients. Based on the above, the effect of diverse antidiabetic
therapies on glycemic control variability and overall management of these
patients to reduce the risk of HFpEF remain essential for the modern
cardiologist.
PMID- 29940224
TI - Multimodality imaging for the detection of ischemia.
PMID- 29940225
TI - The application of dual-electrode through vial impedance spectroscopy for the
determination of ice interface temperatures, primary drying rate and vial heat
transfer coefficient in lyophilization process development.
AB - Through vial impedance spectroscopy (TVIS) is a product non-invasive process
analytical technology which exploits the frequency dependence of the complex
impedance spectrum of a composite object (i.e. the freeze-drying vial and its
contents) in order to track the progression of the freeze-drying cycle. This work
demonstrates the use of a dual electrode system, attached to the external surface
of a type I glass tubing vial (nominal capacity 10 mL) in the prediction of (i)
the ice interface temperatures at the sublimation front and at the base of the
vial, and (ii) the primary drying rate. A value for the heat transfer coefficient
(for a chamber pressure of 270 ubar) was then calculated from these parameters
and shown to be comparable to that published by Tchessalov (2017).
PMID- 29940228
TI - Desperate Measures for Desperate Straits.
PMID- 29940227
TI - Enhanced Recovery After Surgery (ERAS) in Thoracic Surgery.
AB - Enhanced Recovery After Surgery (ERAS) pathways are protocolled collections of
perioperative decisions designed to improve outcomes that are becoming
increasingly popular across surgical subspecialties. In this article, we review 5
recent manuscripts focused on ERAS for elective pulmonary resections, focusing on
the components of the pathways and the resultant outcomes. Overall, we observed
that ERAS protocols can be safely implemented without increasing hospital
readmission or mortality. The benefit is largely seen in shortened length of
stay, though there is some promise for decreasing rates of important
perioperative complications, especially in patients receiving thoracotomies. More
research is needed into the specific elements that impact care, as well as the
effect on overall patient experience.
PMID- 29940226
TI - Design and in vivo evaluation of entecavir-3-palmitate microcrystals for
subcutaneous sustained delivery.
AB - The objectives of this study were to formulate microcrystals of entecavir-3
palmiate (EV-P), a palmitic acid ester of entecavir (EV), and evaluate the
influence of particle size on its pharmacokinetic behavior following subcutaneous
(SC) injection. Systemic toxicity and local tolerability of the hepatitis B anti
viral suspension were further evaluated in normal rats. EV-P microcrystals
possessing median diameters of 2.1, 6.3, and 12.7 um were fabricated using anti
solvent crystallization technique with polysorbate 20 and polyethylene glycol
4000 as steric stabilizer. Dissolution rate of EV-P microcrystals was controlled
by adjusting the particle size, under sink condition. Pharmacokinetic profiles of
2.1 um-sized and 6.3 um-sized EV-P microcrystals were quite comparable (1.44
mg/kg as EV), over 46 days in rats. The absorption rate and extent of EV after SC
injection of 12.7 um-sized microcrystals were significantly retarded, due to its
slower dissolution rate in aqueous media. No single-dose systemic toxicity was
observed after SC injection of high dose of EV-P microcrystal suspension (30-300
mg/kg as EV). The microcrystals were tolerable in the injected site, showing mild
inflammatory responses at a dose of 30 mg/kg. Therefore, the novel microcrystal
system with median particle size of below 6.3 um is expected to be a unique long
acting system of the anti-viral agent, improving patient's compliance with
chronic disease.
PMID- 29940229
TI - Purification, characterization and gene identification of a membrane-bound
glucose dehydrogenase from 2-keto-d-gluconic acid industrial producing strain
Pseudomonas plecoglossicida JUIM01.
AB - The membrane-bound glucose dehydrogenase (mGDH) is a rate-limiting enzyme for the
industrial production of 2-keto-d-gluconic acid (2KGA) from glucose. In this
study, mGDH was firstly purified from a 2KGA industrial producing strain
Pseudomonas plecoglossicida JUIM01. The purified mGDH exhibited a specific
activity of 16.85 U/mg and was identified as monomeric membrane-bound PQQ
dependent dehydrogenase with a molecular mass of ~87 kDa. The Km and Vmax value
of d-glucose were 0.042 mM and 14.620 MUM/min, and the optimal pH and temperature
were of 6.0 and 35 degrees C with favorable acid resistance and poor heat
tolerance. Ca2+/Mg2+ showed a significantly positive effect on mGDH activity with
20% increase, whereas EDTA/EGTA had a negative influence, and Ca2+ was essential
for enzyme activity. Furthermore, a 2412 bp-length gcd was amplified by genome
walking technique and heterologously expressed in Escherichia coli.
Bioinformatics analysis and heterologous expression further confirmed it as a
mGDH encoding gene. mGDH contained binding sites of Ca2+, cofactor PQQ and
polypeptide binding sites concluded from alignment results of mGDHs from
different genera. This study would lay the foundation for improving 2KGA
productivity through further strain modification.
PMID- 29940230
TI - Properties and in vitro drug release of pH- and temperature-sensitive double
cross-linked interpenetrating polymer network hydrogels based on hyaluronic
acid/poly (N-isopropylacrylamide) for transdermal delivery of luteolin.
AB - In this study, we prepared double cross-linked interpenetrating polymer network
(IPN) hydrogels composed of temperature sensitive poly (N-isopropylacrylamide)
(PNIPAM) and pH sensitive hyaluronic acid (HA) by radical polymerization and
Michael addition. Their physicochemical properties for transdermal delivery of
luteolin inhibiting the hyperproliferation of keratinocytes in psoriasis were
investigated and drug release studies were performed. Double networks of
HA/PNIPAM IPN hydrogel were identified through FT-IR and 13CNMR. By measuring the
swelling ratios pH and temperature sensitivity were confirmed, and it was
influenced by the content of a cross-linking agent. As a result of texture
analysis and rheometry, a IPN hydrogel with 3% crosslinker content had the most
adhesive and stable cross-linked network. Therefore, luteolin was loaded on this
hydrogel. Its drug release behavior was determined at various temperatures and pH
using several drug release kinetic models. As a result of skin permeation study,
HA/PNIPAM IPN hydrogel effectively delivers luteolin to the epidermis and dermis.
No toxicity was observed as a result of observing cytotoxicity of the hydrogel
for application to the skin. In conclusion, IPN hydrogels can be developed as
carriers of transdermal delivery system of luteolin for psoriasis skin relief.
PMID- 29940231
TI - Effects of freezing-thawing pretreatment combined with liquid nitrogen and dilute
acid on the gelatinization of collagen.
AB - The method of liquid nitrogen quick-freezing combined with dilute acid rapid
thawing was applied as a pretreatment to extract gelatins from pigskins, and the
influence of HCl concentration (0-2% (v/v)) on the gelatinization of collagen in
pigskins was observed. The freezing-thawing using liquid nitrogen and water did
not effectively induce the gelatinization of collagen, and the replacement of
water with dilute HCl solutions improved this situation. The gelatin pretreated
with liquid nitrogen and 1% HCl showed the highest yield and strongest gel
properties, since the hydrogen bonds balance and the triple-helical structure in
collagen were damaged moderately after this pretreatment to promote the release
of subunit components in collagen during gelatin extraction. The surface of the
gelatinized collagen via freezing-thawing pretreatment with liquid nitrogen and
1% HCl showed a similar honeycomb shape as traditional acid pretreatment.
However, the pretreatment time could be shortened from 6 h (traditional acid
method) to 20 min. Therefore, the freezing-thawing method combined with liquid
nitrogen and dilute acid could be potentially used in gelatin preparation.
PMID- 29940232
TI - Cognitive Versus Software Fusion for MRI-targeted Biopsy: Experience Before and
After Implementation of Fusion.
AB - OBJECTIVE: To compare the diagnostic performance of the 2 most common approaches
of magnetic resonance imaging targeted biopsy (TB)-cognitive registration
targeted biopsy (COG-TB) and software fusion targeted biopsy (FUS-TB)-we assessed
our institutional experience with both methods. TB has emerged to complement
systematic template biopsy (SB) in prostate cancer (PCa) diagnosis; however,
which magnetic resonance imaging targeting methodology is diagnostically better
remains unclear. MATERIALS AND METHODS: A total of 510 patients underwent TB at
our institution before and after the adoption of fusion software with the UroNav
platform (Invivo Corporation, Gainsville, FL). All patients had concurrent 12
core SB. We compared rates of clinically significant PCa detection, and rates of
upstaging and missed diagnosis in reference to SB among patients who received COG
TB and patients who received FUS-TB. We also compared both COG-TB and FUS-TB
results to their paired SB results. RESULTS: The rates of upstaging or missing
clinically significant PCa with FUS-TB (in reference to SB) was not significantly
different from COG-TB (P = 0.172), nor was the risk of missing clinically
significant PCa different between FUS-TB vs COG-TB on logistic regression ( Odds
ratio = 0.55, P = 0.106). No significant difference in biopsy outcomes was
observed between FUS-TB and COG-TB (P = 0.171). We did find significant
differences between FUS-TB and SB and between COG-TB and SB, with SB finding more
clinically insignificant PCa (P < 0.001 and P = 0.04). CONCLUSION: In our
institutional experience, no significant difference was observed between the
diagnostic ability of COG-TB vs FUS-TB for detecting clinically significant PCa.
Greater evidence demonstrating an advantage of FUS-TB over COG-TB would be
required for clear recommendations in favor of FUS-TB.
PMID- 29940233
TI - Disproportionate Use of Inpatient Care by Older Adults With Kidney Stones.
AB - OBJECTIVE: To describe variation in utilization and costs of inpatient care for
patients with kidney stones, examining associations with older age. MATERIALS AND
METHODS: Using the Nationwide Inpatient Sample we examined inpatient discharges
with stone diagnoses from 2007 to 2011. We examined length of stay,
hospitalization cost, and postdischarge care utilization using multivariable
regression to identify associations between patient/hospital characteristics and
resource. RESULTS: An estimated 1.7 million hospital discharges for stone disease
occurred during the study period. Median length of stay was 2.1 days with a
median cost of $6300. Hospital use was substantially higher among persons >=65
years old (older adults) as compared to those aged 18-64 (younger adults): median
length of stay was 3.1 days, with 25% staying more than 5.9 days. Older adults
were significantly more likely to utilize home health (odds ratio [OR] 3.6) or
skilled nursing (OR 5.0) after discharge. Older adults accounted for 1 in 3
hospital discharges, 40% of costs, and half of postdischarge care utilization.
They were more likely to be septic during hospitalization (OR 1.8) which doubled
costs per episode, but less likely to receive surgery (OR 0.93). CONCLUSION:
While historically at lower risk for kidney stones compared to younger adults,
older adults utilizing inpatient care account for a disproportionate share of the
economic burden of disease. Utilization is higher for older adults across
multiple dimensions, including hospital costs, length of stay, and postdischarge
care. These findings suggest that efforts to understand and mitigate the impact
of kidney stones on this vulnerable population are required.
PMID- 29940234
TI - Lifestyle and Progression of Lower Urinary Tract Symptoms in German Men-Results
From the EPIC-Heidelberg Cohort.
AB - OBJECTIVE: To examine if lower urinary tract symptom (LUTS) progression was
related to anthropometric and lifestyle factors. MATERIAL AND METHODS: The
analysis included 5495 men who participated in the EPIC-Heidelberg cohort
(recruited 1994-1998) and who reported an International Prostate Symptom Score <
8 at follow-up 4 (FUP4, 2007-2009), had not reported taking alpha-adrenoreceptor
antagonists or 5-alpha reductase inhibitors or prostate surgery for benign
prostatic hyperplasia/LUTS treatment. LUTS progression was defined as an
International Prostate Symptom Score >= 8 at FUP5 (2010-2012). Using logistic
regression analysis, education, marital status, satisfaction with life,
satisfaction with health, history of diabetes and of hypertension, smoking,
alcohol consumption, body mass index (BMI), waist circumference, and physical
activity were examined as potential LUTS risk factors adjusting for age. RESULTS:
Increase in BMI between baseline and FUP4 of >= 2 BMI units was related to LUTS
progression (odds ratio 1.30, 95% confidence interval 1.08-1.57) compared with
stable BMI. Compared to men who were very satisfied with life at baseline, those
who were satisfied (1.28, 1.11-1.47), unsatisfied (1.80, 1.31-2.46) or very
unsatisfied with life (1.43, 0.62-3.34) were more likely to report LUTS
progression. Men with longer education had higher odds of LUTS progression than
men with primary education only (1.25, 1.06-1.48). Adjusting for BMI or lifestyle
factors did not attenuate these associations. Smoking habits, alcohol
consumption, physical activity, self-reported history of diabetes or
hypertension, and marital status were not related with LUTS progression.
CONCLUSION: Our results confirm some, but not all previously observed risk
factors for LUTS progression.
PMID- 29940235
TI - The neurobiology of the male sexual refractory period.
AB - Despite having been recognized for many years, the mechanisms governing the male
sexual refractory period (post-ejaculatory refractory period, post-ejaculatory
interval) remain poorly understood. This review examines the brain and spinal
areas putatively involved in this phenomenon to draw a coherent picture from the
available data. It is hoped that this will reveal where further research will
offer the potential for crucial insights on this topic.
PMID- 29940236
TI - Modulation of glucocorticoids by the serotonin transporter polymorphism: A
narrative review.
AB - The biological background and consequences of serotonin transporter polymorphism
glucocorticoid relationship in individual differences in stress reactivity has
been a major interest in neuropsychiatry research. Individual differences in
glucocorticoid release have long been implicated in vulnerability to stress
related psychopathologies, like depression and anxiety in various species. Yet,
it is largely elusive to what extent results from non-human primates and rodents
translate to human findings. Based on our structured, comprehensive and non
hypothesis driven overview of this topic, we conclude that although gene
environment interaction studies have highlighted the importance of serotonin
transporter polymorphism in modulating glucocorticoid release, there is
compelling evidence that age, gender and ethnicity are significant factors too
contributing to the equation. We conclude too that the way early life events
modulate an individual's stress reactivity as a function of serotonin transporter
polymorphism is comparable between species. These data provide a rationale for
the design of new, prospective translational studies into sex-specific gene
environment interactions across the lifespan with the goal of improving
preventative efforts and optimizing (personalized) treatment in stress-related
psychopathologies.
PMID- 29940237
TI - Role of Kynurenine pathway and its metabolites in mood disorders: A systematic
review and meta-analysis of clinical studies.
AB - Activation of the kynurenine pathway is one of the described mechanisms by which
inflammation can induce depression. It involves multiple pathways including
interference with the bioavailability of tryptophan central to the synthesis of
the neurotransmitter serotonin. In this systematic review, we examine the
relationship between kynurenine metabolites (kynurenine, kynurenic acid,
tryptophan, quinolinic acid, the ratio of kynurenine and tryptophan) and mood
disorders by conducting a meta-analysis. Fifty-six studies were identified, 21
met inclusion criteria and 14 were deemed suitable (9 investigating unipolar
depression and 5 bipolar disorder). We found decreased levels of kynurenine in
unipolar major depression vs. healthy controls but studies were significantly
heterogeneous in nature. No significant differences were found in tryptophan
levels or kynurenine/tryptophan ratios. Kynurenine metabolites are likely to play
a role in major depression but an exact etiological role in mood disorder seem
complex and requires further research.
PMID- 29940238
TI - Overview of the clinical implementation of a study exploring social withdrawal in
patients with schizophrenia and Alzheimer's disease.
AB - Trans-diagnostic, domain- or symptom-focused approaches have been heralded as
advancing psychiatric research, but relatively few clinical research programmes
have been undertaken to leverage their potential. In this manuscript we describe
the approach and protocol for an exploratory study, PRISM (Psychiatric Ratings
using Intermediate Stratified Markers), that will be conducted to explore the
biomarkers in schizophrenia (SZ) and Alzheimer's Disease (AD) that may be related
to a common symptom, social withdrawal. Patient participants (N = 72 SZ and N =
72 AD study completers), will complete a series of fMRI, EEG, and behavioural
paradigms, as well as contributing blood-derived (e.g. epigenetic) and smartphone
data related to social behaviour. Self- as well as caregiver- and researcher
reported assessments will be provided to characterise social withdrawal.
Normative data will also be collected from a group of healthy controls (N = 48
study completers), half of whom will be matched in terms of age and gender
distribution to the SZ and AD group, respectively. Thus we will explore both
differentiation and cross-diagnostic overlap in the biomarkers associated with
different levels of social withdrawal in SZ and AD. In this way we aim to provide
a deeper understanding of the biological underpinnings of symptomatology common
to both disorders, and provide insights into novel treatment targets and future
drug development approaches.
PMID- 29940239
TI - A systematic review and meta-analysis of structural magnetic resonance imaging
studies investigating cognitive and social activity levels in older adults.
AB - Population aging has prompted considerable interest in identifying modifiable
factors that may help protect the brain and its functions. Collectively,
epidemiological studies show that leisure activities with high mental and social
demands are linked with better cognition in old age. The extent to which socio
intellectual activities relate to the brain's structure is, however, not yet
fully understood. This systematic review and meta-analysis summarizes magnetic
resonance imaging studies that have investigated whether cognitive and social
activities correlate with measures of gray and white matter volume, white matter
microstructure and white matter lesions. Across eighteen included studies (total
n = 8429), activity levels were associated with whole-brain white matter volume,
white matter lesions and regional gray matter volume, although effect sizes were
small. No associations were found for global gray matter volume and the evidence
concerning white matter microstructure was inconclusive. While the causality of
the reviewed associations needs to be established, our findings implicate socio
intellectual activity levels as promising targets for interventions aimed at
promoting healthy brain aging.
PMID- 29940240
TI - Protective effects of magnesium sulfate against doxorubicin induced
cardiotoxicity in rats.
AB - AIMS: Clinical use of doxorubicin, an effective chemotherapeutic agent, has
limited uses due to dose-dependent cardiac toxicity. It has been supposed that
the production of free radicals and calcium ions overload can lead to cardiac
toxicity. Magnesium is a cardioprotective drug which inhibits lipid peroxidation
and reducing myocardial apoptosis. This study was aimed to explore the hypothesis
that the cardiac toxicity induced by administration of doxorubicin is prevented
or reduced by magnesium sulfate treatment and if so, whether this is associated
with altered oxidative stress response in heart. MATERIAL AND METHODS: Male
Wistar rats were intraperitoneally injected with doxorubicin and magnesium
sulfate and normal saline four times per week for 2 consecutive weeks. Then
electrocardiographic, inotropic and biochemical tests were performed. KEY
FINDINGS: Co-administration of magnesium sulfate with doxorubicin significantly
reversed alterations in the stimulation threshold and contractile force induced
by doxorubicin. In addition, magnesium sulfate improved body weight loss and
alleviated the mortality rate of animals induced by doxorubicin. Moreover, it was
observed that lesions induced by doxorubicin decreased in animals treated with
magnesium sulfate. Magnesium sulfate significantly increased Glutathione (GSH) in
doxorubicin treated animals. SIGNIFICANCE: In conclusion, the results of the
present study demonstrated that magnesium sulfate attenuate the cardio toxic
effects of doxorubicin by increasing the activities of the antioxidants enzyme.
PMID- 29940241
TI - Fibulin-1 interacts with Sex Hormone Binding Globulin and is linked to less
aggressive estrogen-dependent breast cancers.
AB - AIMS: Interaction of Sex Hormone-Binding Globulin (SHBG) with estrogen-sensitive
breast cancer cells has a protective role against estrogen exposure. No specific
membrane receptor for SHBG had been identified by now, but a putative interaction
of SHBG with extracellular matrix associated-proteins (e.g. fibulins) was
suggested. In this study we investigated the expression of fibulins, their
functional relationship with SHBG and involvement in behavior of estrogen
sensitive breast cancer. MAIN METHODS: Gene expression of fibulins was performed
by Real time-PCR on two estrogen-sensitive breast cancer cell lines, MCF-7 and
T47D. Fibulin-1 protein expression and localization were determined by Western
blot and immunofluorescence. SHBG interaction with-fibulin-1 was assessed by GST
pull down assay. MCF-7 cell growth and gene expression, after fibulin-1 silencing
by siRNA, were evaluated. Finally, the expression of fibulin-1 was correlated to
clinical and pathological data of 21 breast cancer tissue samples. KEY FINDINGS:
Fibulin-1 was expressed in both cell lines and it was increased by estradiol.
SHBG interacted with fibulin-1C; proteins co-localized at MCF-7 cell membranes
and SHBG localization at membranes disappeared after silencing fibulin-1. Fibulin
1 silencing, moreover, generated MCF-7 cells unresponsive to estradiol and SHBG
and characterized by increased proliferation. Finally, in breast cancer tissue
samples expressing fibulin-1 the proliferation index was significantly lower than
in fibulin-1 negative samples. SIGNIFICANCE: Fibulin-1 interacts with SHBG, it is
associated with a less aggressive behavior of breast cancer cells and correlates
to a better prognosis of the tumor.
PMID- 29940242
TI - Novel multi-target directed ligand-based strategies for reducing
neuroinflammation in Alzheimer's disease.
AB - Alzheimer's disease (AD) is one of the most common causes of dementia. AD
pathogenesis has been hypothesized to involve cholinergic deficits, amyloid-beta
protein (Abeta) deposition, tau protein hyperphosphorylation, and chronic
neuroinflammation. Many single-target drugs have gone through the various stages
of pre-clinical and clinical development in an effort to cure AD; however, the
current clinically approved drugs have only limited effects on the disease
progression. With the accumulation of unsuccessful clinical trials using single
target drugs, multi-target directed ligand (MTDL) drug development is becoming
more common. MTDLs incorporate two or more pharmacophores into a single drug
molecule. This approach can alleviate side effects and lead to a better
pharmacokinetic profile of the MTDL compared to two or more separate drugs
representing respective single pharmacophores. This review discusses cathepsin B
(CatB), dual specificity phosphatase 2 (DUSP2), and monoglycerol lipase (MAGL) as
targets for MTDLs aimed at slowing down the neuroinflammatory component of
neurodegenerative diseases. CatB, DUSP2 and MAGL inhibitors show promising
preclinical anti-inflammatory effects in vivo and in vitro. Incorporating
pharmacophores that inhibit these targets into MTDLs represents a promising
avenue towards effective suppression of neuroinflammation associated with AD.
PMID- 29940244
TI - Sonodynamic therapy: A potential treatment for atherosclerosis.
AB - Atherosclerosis (AS), a chronic arterial disease, is one of the major causes of
morbidity and mortality worldwide. Several treatment modalities have been
demonstrated to be effective in treating AS; however, the mortality rate due to
AS remains high. Sonodynamic therapy (SDT) is a promising new treatment using low
intensity ultrasound in combination with sonosensitizers. Although SDT was
developed from photodynamic therapy (PDT), it has a stronger tissue-penetrating
capability and exhibits a more focused effect on the target lesional site
requiring treatment. Furthermore, SDT has been demonstrated to suppress the
formation of atheromatous plaques, and it can increase plaque stability both in
vitro and in vivo. In this article, we critically summarize the recent literature
on SDT, focusing on its possible mechanism of action as well as the existing and
newly discovered sonosensitizers and chemotherapeutic agents for the treatment of
AS.
PMID- 29940245
TI - Examination of the Clostridioides (Clostridium) difficile VanZ ortholog, CD1240.
AB - Clostridioides (Clostridium) difficile causes severe diarrheal disease that is
directly associated with antibiotic use and resistance. Although C. difficile
demonstrates intrinsic resistance to many antimicrobials, few genetic mechanisms
of resistance have been characterized in this pathogen. In this study, we
investigated the putative resistance factor, CD1240 (VanZ1), an ortholog of the
teicoplanin resistance factor, VanZ, of Enterococcus faecium. In C. difficile,
the vanZ1 gene is located within the skin element of the sporulation factor
sigmaK, which is excised from the mother cell compartment during sporulation.
This unique localization enabled us to create a vanZ1 deletion mutant by inducing
excision of the skin element. The Deltaskin mutant exhibited moderately decreased
resistance to teicoplanin and had small effects on growth in some other cell
surface antimicrobials tested. Examination of vanZ1 expression revealed induction
of vanZ1 transcription by the antimicrobial peptide LL-37; however, LL-37
resistance was not impacted by VanZ1, and none of the other tested antimicrobials
induced vanZ1 expression. Further, expression of vanZ1 via an inducible promoter
in the Deltaskin mutant restored growth in teicoplanin. These results demonstrate
that like the E. faecium VanZ, C. difficile VanZ1 contributes to low-level
teicoplanin resistance through an undefined mechanism.
PMID- 29940243
TI - Tumor necrosis factor-alpha upregulated PHLPP1 through activating nuclear factor
kappa B during myocardial ischemia/reperfusion.
AB - AIMS: The pleckstrin homology domain leucine-rich repeat protein phosphatase 1
(PHLPP1) specifically regulates phospho-Ser473 of protein kinase B (PKB, Akt)
opposing cell survival during myocardial ischemia/reperfusion (I/R). Previous
studies demonstrated PHLPP1 expression level was controlled by several
mechanisms. However, the regulation mechanism of cardiac PHLPP1 expression
following myocardial I/R remains unknown. MAIN METHODS: The current study
utilized the mouse model of myocardial I/R injury in vivo and the neonatal rat
ventricular myocytes (NRVMs) of hypoxia/reoxygenation (H/R) injury in vitro.
Expression of PHLPP1, nuclear factor-kappa B (NF-kappaB) and pNF-kappaB were
determined by western blot. The expression of PHLPP1 and translocation of NF
kappaB was assessed by immunofluorescence. Chromatin immunoprecipitation (ChIP)
assay was used to detect the binding of NF-kappaB to the promoter region of
phlpp1 gene. KEY FINDINGS: Myocardial I/R had no effect on cardiac PHLPP1
expression following I/R (30 min/2 h) but decreased after 4 h reperfusion. In
vitro, H/R (4 h/1 h) and tumor necrosis factor-alpha (TNF-alpha)-stimulation
resulted in upregulation of PHLPP1 in NRVMs, which was blocked with etanercept.
Yet, H2O2-induced oxidative stress had no obvious effect on PHLPP1 expression of
NRVMs at early stage but N-acetylcysteine (NAC) pretreatment increased PHLPP1
levels after 4 h H2O2 stimulation. TNF-alpha and H/R led to both expression and
transcriptional activity of NF-kappaB, accompany with higher expression of
PHLPP1. Pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, prevented the
response not only in TNF-alpha-treated cardiomyocytes but also in H/R-treated
group. SIGNIFICANCE: These results implicated that TNF-alpha involved in cardiac
PHLPP1 upregulation during reoxygenation, which was mediated by NF-kappaB
transcriptional activity.
PMID- 29940246
TI - Treatment and Prevention of Recurrent Lower Urinary Tract Infections in Women: A
Rapid Review with Practice Recommendations.
AB - PURPOSE: Recurrent lower urinary tract infections in women are a highly prevalent
and burdensome condition for which best practice guidelines for treatment and
prevention that minimize harm and optimize well-being are greatly needed. To
inform development of practice recommendations, a rapid literature review of
original research, systematic reviews, meta-analyses and practice guidelines was
conducted. MATERIALS AND METHODS: PubMed(r), Embase(r), Opus, Scopus(r), Google
Scholar, The Cochrane Library and the U.S. National Guideline Clearinghouse
electronic databases were searched from inception to September 22, 2017. Articles
and practice guidelines were included if they were in English, were peer
reviewed, included women, involved treatment or prevention strategies for
recurrent urinary tract infection and reported an outcome related to recurrence
rates of urinary tract infection. Critical appraisal of original studies was
conducted using the Cochrane risk of bias tool, and of systematic reviews using
the AMSTAR 2 tool. RESULTS: Of 1,582 citations identified 74 met our study
inclusion criteria. These comprised 49 randomized controlled trials, 23
systematic reviews (16 with meta-analyses) and 2 practice guidelines. No study
reported a multi-targeted treatment approach. There was a lack of high quality
studies and systematic reviews evaluating prevention strategies for recurrent
urinary tract infection. CONCLUSIONS: We recommend an algorithmic approach to
care that includes education on lifestyle and behavioral modifications, and
addresses specific populations of women with antimicrobial based and
nonantibiotic alternatives. This approach includes the use of vaginal estrogen
with or without lactobacillus containing probiotics in postmenopausal women, low
dose post-coital antibiotics for recurrent urinary tract infection associated
with sexual activity in premenopausal women, low dose daily antibiotic
prophylaxis in premenopausal women with infections unrelated to sexual activity,
and methenamine hippurate and/or lactobacillus containing probiotics as
nonantibiotic alternatives. Future research should involve consistent use of
terminology, validated instruments to assess response to interventions and
patient perspectives on care. Our treatment algorithm is based on the best
available evidence, and fills a gap in the literature and practice regarding
effective strategies to prevent recurrent urinary tract infection in women.
PMID- 29940247
TI - Short-Term Changes in Urinary Relative Supersaturation Predict Recurrence of
Kidney Stones: A Tool to Guide Preventive Measures in Urolithiasis.
AB - PURPOSE: Kidney stone disease is characterized by a relatively high rate of
recurrence. In our study we analyzed the association between relative
supersaturation and the risk of stone recurrence. Additionally, we examined the
association between the risk of recurrence and changes in relative
supersaturation and urinary composition after 1 week of medical treatment.
MATERIALS AND METHODS: We performed a post hoc analysis of data from a previously
published randomized controlled trial comparing the effect of 2 diets in 120 men
with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup
24-hour urine parameters were used to calculate the relative supersaturation of
calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and
LithoRisk computer programs. Cox models were used to calculate the estimated
association between each baseline relative supersaturation, and 1-week changes
and the risk of recurrence during followup. RESULTS: During a 5-year followup 35
patients (34%) experienced recurrence. A reduction in calcium oxalate relative
supersaturation at 1 week was significantly associated with a lower risk of
recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR
0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for
relative supersaturation calculated by other methods or for the relative
supersaturation of other salts. Changes in the 24-hour urine excretion of
citrate, potassium and magnesium were significantly associated with a risk of
recurrence. CONCLUSIONS: In recurrent stone formers with hypercalciuria baseline
values and changes in the relative supersaturation of calcium oxalate may be
associated with the risk of recurrence. Changes in urinary citrate, potassium and
magnesium following dietary intervention may also be predictive.
PMID- 29940248
TI - Comparison of Elastic and Rigid Registration during Magnetic Resonance
Imaging/Ultrasound Fusion-Guided Prostate Biopsy: A Multi-Operator Phantom Study.
AB - PURPOSE: The relative value of rigid or elastic registration during magnetic
resonance imaging/ultrasound fusion guided prostate biopsy has been poorly
studied. We compared registration errors (the distance between a region of
interest and fiducial markers) between rigid and elastic registration during
fusion guided prostate biopsy using a prostate phantom model. MATERIALS AND
METHODS: Four gold fiducial markers visible on magnetic resonance imaging and
ultrasound were placed throughout 1 phantom prostate model. The phantom underwent
magnetic resonance imaging and the fiducial markers were labeled as regions of
interest. An experienced user and a novice user of fusion guided prostate biopsy
targeted regions of interest and then the corresponding fiducial markers on
ultrasound after rigid and then elastic registration. Registration errors were
compared. RESULTS: A total of 224 registration error measurements were recorded.
Overall elastic registration did not provide significantly improved registration
error over rigid registration (mean +/- SD 4.87 +/- 3.50 vs 4.11 +/- 2.09 mm, p =
0.05). However, lesions near the edge of the phantom showed increased
registration errors when using elastic registration (5.70 +/- 3.43 vs 3.23 +/-
1.68 mm, p = 0.03). Compared to the novice user the experienced user reported
decreased registration error with rigid registration (3.25 +/- 1.49 vs 4.98 +/-
2.10 mm, p <0.01) and elastic registration (3.94 +/- 2.61 vs 6.07 +/- 4.16 mm, p
<0.01). CONCLUSIONS: We found no difference in registration errors between rigid
and elastic registration overall but rigid registration decreased the
registration error of targets near the prostate edge. Additionally, operator
experience reduced registration errors regardless of the registration method.
Therefore, elastic registration algorithms cannot serve as a replacement for
attention to detail during the registration process and anatomical landmarks
indicating accurate registration when beginning the procedure and before
targeting each region of interest.
PMID- 29940250
TI - Psychosocial and Sexual Outcomes in Adolescents following Surgery for Proximal
Hypospadias in Childhood.
AB - PURPOSE: We evaluated psychosocial outcomes, psychosexual development and sexual
function in adolescents who had undergone surgery for proximal hypospadias. We
hypothesized that these outcomes would be impaired compared to peers. MATERIALS
AND METHODS: We identified 55 males age 14 years or older who underwent surgery
for penoscrotal to perineal (intraoperatively defined) hypospadias between 1996
and 2005. A total of 33 patients with a median age of 17.5 years (range 14 to 25)
answered a Web based questionnaire with self-constructed questions, completed the
validated Psychological General Well-Being Index, Body-Esteem Scale for
Adolescents and Adults and Penile Perception Score, and underwent clinical
evaluation. A total of 31 patients with distal hypospadias (median age 19 years,
range 14 to 35) and 25 age matched healthy men (17.5 years, range 14 to 25)
served as controls. RESULTS: Interest in sex, age at sexarche and satisfaction
with sexual experiences were comparable between patients and controls. Three
patients with proximal hypospadias (10%) and 1 control (4%) reported occasional
erectile problems. Three patients with proximal hypospadias (11%), 1 patient with
distal hypospadias (3%) and 1 control (4%) affirmed anejaculation. There were no
differences in results between validated questionnaires. Patients with proximal
hypospadias were more dissatisfied with penile length (39%) compared to controls
(12%, p = 0.049). Concerning physical contact, 10 patients (38%) expressed
uncertainty. Extra support in school was more frequent among patients with
proximal hypospadias (p = 0.024 vs distal hypospadias, p = 0.068 vs control
group). CONCLUSIONS: Despite concerns regarding penile length, sexual experiences
were comparable to those of other adolescents, although more than a third of
patients with proximal hypospadias demonstrated uncertainty on questions relating
to desire for physical contact. Specialized tutoring in school was more common in
patients with proximal hypospadias. Continuous followup throughout childhood
allowing extra time for age adequate information and support is warranted.
PMID- 29940249
TI - Changeable Conditional Survival Rates and Associated Prognosticators in Patients
with Metastatic Renal Cell Carcinoma Receiving First Line Targeted Therapy.
AB - PURPOSE: In this study we evaluated conditional survival probabilities in
patients with metastatic renal cell carcinoma who underwent first line tyrosine
kinase inhibitor therapy. We also identified predictors of conditional survival
with time. MATERIALS AND METHODS: We retrospectively reviewed clinical data on
1,659 individuals with metastatic renal cell carcinoma in the Korean Renal Cancer
Study Group database, of whom the records of 1,131 were finally analyzed. The
primary end point was conditional overall survival. Kaplan-Meier survival
analysis was used to calculate conditional overall survival probabilities using
the formula, conditional survival (alpha?beta) = S(alpha + beta)/S(beta),
indicating the likelihood of additional alpha years survivorship in person who
has already survived for beta years after initial therapy. S(chi) represents the
actual survival rate. Multivariate Cox regression model was used to identify
predictors of conditional survival with time. RESULTS: Six, 12, 18, 24 and 36
month conditional overall survival gradually increased in patients at all
additional survival times after initial treatment compared to patient baseline
survival estimations. While the actual overall survival rate decreased with time,
the 36-month conditional overall survival rate was calculated as 7.3% higher in
patients who had already survived 36 months compared to baseline estimations at
the time of initial tyrosine kinase inhibitor treatment. Furthermore, predictors
of conditional overall survival changed with time. Only previous metastasectomy
remained a key prognosticator of conditional overall survival until 36 months of
survival following initial tyrosine kinase inhibitor treatment. CONCLUSIONS:
Conditional survival improved with time after initial tyrosine kinase inhibitor
treatment in patients with metastatic renal cell carcinoma. Our study offers
valuable information for practical survival estimations and relevant
prognosticators in patients with metastatic renal cell carcinoma who receive
first line tyrosine kinase inhibitor.
PMID- 29940251
TI - Patient Reported Outcome Measures for Transperineal Template Prostate Mapping
Biopsies in the PICTURE Study.
AB - PURPOSE: Transperineal template prostate mapping biopsy is an increasingly used
method of procuring tissue from men with suspected prostate cancer. We report
patient related outcome measures and adverse events in men in the PICTURE trial
(ClinicalTrials.gov NCT01492270) who underwent this diagnostic test. MATERIALS
AND METHODS: A total of 249 men underwent multiparametric magnetic resonance
imaging followed by transperineal template prostate mapping biopsy as a
validation study. Functional outcomes before and after transperineal template
prostate mapping were prospectively collected and recorded with questionnaires,
including the I-PSS (International Prostate Symptom Score), the I-PSS-QoL
(Quality of Life), the IIEF-15 (International Index of Erectile Function-15) and
the EPIC (Expanded Prostate Cancer Index Composite) urinary function. RESULTS:
Mean age was 62 years, median prostate specific antigen was 6.8 ng/ml and median
gland size was 37 ml. At transperineal template prostate mapping biopsy a median
of 49 cores (IQR 40-55) were taken. Mean time to complete the post-procedure
patient related outcome measure questionnaires was 46 days. Adverse events
included post-procedure acute urinary retention in 24% of patients, rectal pain
in 26% and perineal pain in 41%. Transperineal template prostate mapping biopsy
resulted in a statistically significant increase in scores on the I-PSS from 10.9
to 11.8 (p = 0.024) and the I-PSS-QoL from 1.57 to 1.76 (p = 0.03). The IIEF-15
erectile function score decreased by 23.2% from 47.7 to 38.7 (p <0.001).
Significant deterioration was noted in all 5 of IIEF-15 functional domains,
including erectile and orgasmic function, sexual desire, and intercourse and
overall satisfaction (p <0.001). EPIC urinary scores showed no overall change
from baseline. CONCLUSIONS: Transperineal template prostate mapping biopsy causes
a high urinary retention rate and a detrimental impact on genitourinary
functional outcomes, including deterioration in urinary flow and sexual function.
Our findings can be used to ensure adequate counseling about transperineal
template prostate mapping biopsies. The results point to a need for strategies
such as multiparametric magnetic resonance imaging and targeted biopsies to
minimize the harms of transperineal template prostate mapping biopsy.
PMID- 29940252
TI - Metformin Use is Associated with Improved Survival for Patients with Advanced
Prostate Cancer on Androgen Deprivation Therapy.
AB - PURPOSE: Metformin is commonly prescribed for patients with type 2 diabetes
mellitus. We hypothesized that metformin plus androgen deprivation therapy may be
beneficial in combination. Our objective was to assess this combination in a
retrospective cohort of patients with advanced prostate cancer. MATERIALS AND
METHODS: Using national Veterans Affairs databases we identified all men
diagnosed with prostate cancer between 2000 and 2008 who were treated with
androgen deprivation therapy with followup through May 2016. Study exclusions
included treatment with androgen deprivation therapy for 6 months or longer, or
receipt of androgen deprivation therapy concurrently with localized radiation.
Three patient cohorts were developed, including no diabetes mellitus, diabetes
mellitus with no metformin and diabetes mellitus with metformin. Cox proportional
HRs were calculated for overall survival, skeletal related events and cancer
specific survival. RESULTS: After exclusions the cohort consisted of 87,344
patients, including 61% with no diabetes mellitus, 22% with diabetes mellitus and
no metformin, and 17% with diabetes mellitus on metformin. Cox proportional
hazard analysis of overall survival showed improved survival in men with diabetes
mellitus on metformin (HR 0.82, 95% CI 0.78-0.86) compared to those with diabetes
mellitus who were not on metformin (HR 1.03, 95% CI 0.99-1.08). The reference
group was men with no diabetes mellitus. Cox proportional hazard analysis of
predictors of skeletal related events revealed a HR of 0.82 (95% CI 0.72-0.93) in
men with diabetes mellitus on metformin. Cox proportional hazard analysis of
cancer specific survival showed improved survival in men with diabetes mellitus
on metformin (HR 0.70, 95% CI 0.64-0.77) vs those with diabetes mellitus without
metformin (HR 0.93, 95% CI 0.85- 1.00). The reference group was men with no
diabetes mellitus. CONCLUSIONS: Metformin use in veterans with prostate cancer
who receive androgen deprivation therapy is associated with improved oncologic
outcomes. This association should be evaluated in a prospective clinical trial.
PMID- 29940253
TI - Complications and Interventions in Patients with an Artificial Urinary Sphincter:
Long-Term Results.
AB - PURPOSE: The artificial urinary sphincter is a common treatment of male urinary
incontinence. We sought to characterize long-term rates of artificial urinary
sphincter revision/removal and reimplantation, and associated risk factors.
MATERIALS AND METHODS: We performed a population based, retrospective study using
the Ontario Health Insurance Plan database of all male patients who underwent
artificial urinary sphincter implantation from 1994 to 2013. Hospital, diagnostic
and billing codes were used to identify patients. The Kaplan-Meier method and
multivariable Cox proportional hazards models were applied to examine the
cumulative incidence of artificial urinary sphincter reimplantation and
revision/removal, and identify risk factors, respectively. RESULTS: A total of
1,632 male patients underwent initial implantation of an artificial urinary
sphincter. The 10-year revision/removal and reimplantation rates were 34% and
27%, respectively. There was no difference between high and low volume hospitals
or between community and academic hospitals in terms of revision/removal. A high
level of comorbidity was associated with an increasing risk of removal/revision.
The reimplantation rate was significantly lower in patients who underwent
insertion at hospitals with the highest volume of surgery (HR 0.55, 95% CI 0.37
0.82, p <0.01). A high level of comorbidity was not associated with an increasing
risk of reimplantation. Preimplantation radiotherapy was not significantly
associated with the risk of reimplantation (p = 0.17) or revision/removal (p =
0.95). Other factors were not significantly associated with reimplantation or
revision/removal. CONCLUSIONS: Most men who undergo artificial urinary sphincter
placement still have a device without repeat surgery 10 years following
insertion. Radiotherapy does not increase the risk of repeat surgery. A high
level of comorbidity was associated with an increasing risk of removal/revision.
PMID- 29940254
TI - Optogenetic suppression of the nucleus reuniens selectively impairs encoding
during spatial working memory.
AB - The nucleus reuniens (Re) of the ventral midline thalamus is known to be a
critical anatomical link between the hippocampus (HPC) and the medial prefrontal
cortex (mPFC). Consistent with this anatomical connectivity, the Re has been
shown to be crucial for HPC-mPFC oscillatory synchrony. Moreover, Re inhibition
consistently results in spatial working memory (SWM) deficits. Together, these
results suggest that SWM requires HPC-mPFC synchrony via the Re. In spite of
these findings, an understanding of how the Re contributes to the encoding,
maintenance, and retrieval of spatial information during a SWM task is lacking.
To address this issue, we trained rats to perform a SWM-dependent delayed-non
match-to-position (DNMP) task in a T-maze. Using optogenetic inhibition of Re
activity, we demonstrated that Re suppression during the sample phase, but not
the delay or choice phase, significantly decreased choice accuracy. We conclude
that the Re contributes to the encoding of spatial information during working
memory.
PMID- 29940255
TI - Suppressing cortisol at encoding reduces the emotional enhancement in subjective
sense of recollection.
AB - The stress hormone cortisol, released when encountering an emotional event,
contributes to form a strong emotional memory. Such emotionally arousing memories
are recalled with an enhanced subjective sense of recollection, i.e. experienced
in memory as more vivid and richer in details. We examined here whether cortisol
plays a role in this emotional enhancement in subjective sense of recollection
for a set of learned scenes. Suppressing cortisol at encoding decreased the
emotional enhancement in subjective sense of recollection at a test 28 h later,
but did not affect familiarity and memory for a contextual detail. Individual
cortisol levels were significantly correlated to emotional enhancement in
subjective sense of recollection. These findings indicate that cortisol plays a
modulatory role for enhanced subjective sense of recollection for emotional
events.
PMID- 29940257
TI - Territorial responses to song components in a suboscine, the vermilion
flycatcher.
AB - Vermilion flycatchers songs are composed of two acoustically different parts: a
first part (FP) containing a variable number of introductory elements, and a
second part (SP) composed of four elements. Previous work suggests that the FP is
important for territorial competition and that it conveys information on threat
level. By exposing free-living males to playbacks of complete songs (CS's), FP's
and SP's, we evaluated the relative contribution of each song part in males'
territorial responses. Males called in response to all three treatments,
suggesting each song component is important for territorial competition. Males'
call response did not differ toward CS's and FP's, and toward CS's and SP's
(although a non-significant tendency was found for SP's to elicit a weaker
response than CS's), but it was greater toward FP's than toward SP's. These
results, coupled with previous work, further support the idea that the FP plays a
special role during territorial competition and may give information on level of
threat. We further discuss our result in terms of mechanistic and functional
hypotheses.
PMID- 29940256
TI - Improved phylogenetic resolution within Siphonophora (Cnidaria) with implications
for trait evolution.
AB - Siphonophores are a diverse group of hydrozoans (Cnidaria) that are found at most
depths of the ocean - from the surface, like the familiar Portuguese man of war,
to the deep sea. They play important roles in ocean ecosystems, and are among the
most abundant gelatinous predators. A previous phylogenetic study based on two
ribosomal RNA genes provided insight into the internal relationships between
major siphonophore groups. There was, however, little support for many deep
relationships within the clade Codonophora. Here, we present a new siphonophore
phylogeny based on new transcriptome data from 29 siphonophore species analyzed
in combination with 14 publicly available genomic and transcriptomic datasets. We
use this new phylogeny to reconstruct several traits that are central to
siphonophore biology, including sexual system (monoecy vs. dioecy), gain and loss
of zooid types, life history traits, and habitat. The phylogenetic relationships
in this study are largely consistent with the previous phylogeny, but we find
strong support for new clades within Codonophora that were previously unresolved.
These results have important implications for trait evolution within
Siphonophora, including favoring the hypothesis that monoecy arose at least
twice.
PMID- 29940260
TI - Peripersonal and extrapersonal visuospatial neglect in different frames of
reference: A brain lesion-symptom mapping study.
AB - INTRODUCTION: Visuospatial neglect can occur in peripersonal and extrapersonal
space. The dorsal visual pathway is hypothesized to be associated with
peripersonal, and the ventral pathway with extrapersonal neglect. We aimed to
evaluate neural substrates of peripersonal versus extrapersonal neglect,
separately for egocentric and allocentric frames of reference. METHODS: This was
a retrospective study, including stroke patients admitted for inpatient
rehabilitation. Approximately 1 month post-stroke onset, computerized
cancellation (egocentric) and bisection tasks (egocentric and allocentric) were
administered at 30 cm and 120 cm. We collected CT or MRI scans and performed
voxel-based lesion-symptom mapping for the cancellation, and subtraction analyses
for the line bisection task. RESULTS: We included 98 patients for the
cancellation and 129 for the bisection analyses. The right parahippocampal gyrus,
hippocampus, and thalamus were associated with egocentric peripersonal neglect as
measured with cancellation. These areas were also associated with extrapersonal
neglect, together with the right superior parietal lobule, angular gyrus,
supramarginal gyrus, lateral occipital cortex, planum temporale and superior
temporal gyrus. Lesions in the right parietal, temporal and frontal areas were
associated with both peripersonal and extrapersonal egocentric neglect as
measured with bisection. For allocentric neglect no clear pattern of associated
brain regions was observed. DISCUSSION: We found right hemispheric anatomical
correlates for peripersonal and extrapersonal neglect. However, no brain areas
were uniquely associated with peripersonal neglect, meaning we could not
conclusively verify the ventral/dorsal hypothesis. Several areas were uniquely
associated with egocentric extrapersonal neglect, suggesting that these brain
areas can be specifically involved in extrapersonal, but not in peripersonal,
attention processes.
PMID- 29940258
TI - Clinical characteristics and prognostic significance of galectins for patients
with gastric cancer: A meta-analysis.
AB - OBJECTIVE: To explore the relationships between the expression level of different
galectins and its prognostic value for patients with gastric cancer. METHODS: The
PubMed, EMbase, the Cochrane Library and Web of Science databases were
systematically searched. All the eligible studies were included according to the
inclusion and exclusion criteria. All the relevant data was extracted by two
independent researchers. The quality assessment was conducted according to the
evaluation of the quality of prognosis study which published by Harden in 2006.
The STATA 12.0 software was used to perform a meta-analysis. RESULTS: All of 8
retrospective case-controlled studies involving 2093 patients with gastric cancer
were included in this study. The results of meta-analysis presented that the
elevated galectin-1 which is related to the poor overall survival (HR = 1.85, 95%
CI: 1.33-2.58; P < 0.001) may predicted a larger tumor size (OR = 2.20, 95% CI:
1.35-3.35; P = 0.001) and was positively associated with the higher expression of
VEGF (OR = 1.44, 95% CI: 1.14-1.82; P = 0.002). Moreover, the decreased galectin
3 (HR = 0.49, 95% CI: 0.36-0.67; P < 0.001), galectin-8 (HR = 0.49, 95% CI: 0.36
0.67; P < 0.001) and galectin-9 (HR = 0.78, 95% CI: 0.66-0.92; P = 0.003) were
also significantly associated with poorer prognosis. Our meta-analysis also
showed that lower expression of galectin-3 was also related to lymphatic vessel
invasion (OR = 0.48, 95% CI: 0.26-0.89; P = 0.018), worse TNM stages (OR = 0.47,
95% CI: 0.32-0.40; P < 0.001), deeper invasive depth (OR = 0.33, 95% CI: 0.21
0.51; P < 0.001) and poorer differentiation grade (OR = 0.10, 95% CI: 0.04-0.25;
P < 0.001). CONCLUSIONS: High expression of galectin-1 or low expression of
galectin-3, -8 and -9 were significantly related to a poorer prognosis for
patients with gastric cancer. The expression level of galectins was associated
with clinical characteristics and were potential independent prognostic predictor
for GC patients.
PMID- 29940259
TI - Oncological outcomes of laparoscopic versus open surgery in pT4 colon cancers: A
systematic review and meta-analysis.
AB - BACKGROUND: Widespread adoption of minimally invasive surgery for colon cancer
has achieved improved short-term benefits and better long-term oncological
outcomes compared with open surgery. However, it is still controversial whether
laparoscopic surgery is suitable for patients with stage T4 colon cancer. The aim
of this meta-analysis was to compare short- and long-term oncological outcomes
associated with laparoscopic and conventional open surgery for pT4 colon cancer.
METHODS: Published studies from 2003 to 2018 comparing oncological outcomes
following laparoscopic and open surgery for pT4 colon cancer were systematically
searched. Data on conversion rate, R0 resection rate, number of harvested lymph
nodes, morbidity and mortality, and overall survival (OS) and disease-free
survival (DFS) were subjected to meta-analysis using fixed-effect and random
effect models. RESULTS: Twelve observational studies met the inclusion criteria
with a total of 2396 cases (1250 laparoscopic and 1146 open). There was no
significant difference in R0 resection rate [relative risk (RR) = 1.007; 95%
confidence interval (CI) = 0.935-1.085; P = 0.850], number of harvested lymph
nodes (MD = 0.004; 95% CI = -0.139 to 0.148; P = 0.951), mortality (RR = 0.509;
95% CI = 0.176-1.470; P = 0.212), and 3-year OS (RR = 1.056; 95% CI = 0.939
1.188; P = 0.360), 5-year OS (RR = 1.003; 95% CI = 0.883-1.139; P = 0.966), 3
year DFS (RR = 1.032; 95% CI = 0.903-1.179; P = 0.642), and 5-year DFS (RR =
0.995; 95% CI = 0.868-1.140; P = 0.973) between the groups. The rate of
conversion from laparoscopic to open procedures was 10.7% (95% CI = 0.090-0.124).
There was a significant difference in incidence of complications within 30
postoperative days between laparoscopic and open surgery (RR = 0.703; 95% CI =
0.564-0.876; P = 0.002). CONCLUSION: Laparoscopic surgery is safe and feasible in
pT4 colon cancer, oncological outcomes are similar, and more importantly, there
are fewer postoperative complications compared with open surgery.
PMID- 29940261
TI - Neural correlates of glucocorticoids effects on autobiographical memory retrieval
in healthy women.
AB - It is well known that elevated cortisol after stress or after exogenous
administration impairs episodic memory retrieval including autobiographical
memory (AM) retrieval. This impairment might be mediated by deactivation of a
neural network associated with memory retrieval including the prefrontal cortex
(PFC) and limbic structures. However, the neural underpinnings of these cortisol
effects on AM retrieval have not been investigated yet. In this study, thirty
three healthy women received either placebo or 10 mg hydrocortisone in a double
blind cross-over design before completing an AM test during fMRI. In this test,
participants are asked to recall specific events from their own past in response
to a cue word. In a first step, we analyzed the neural underpinnings of AM
retrieval in the placebo condition. We found an activation pattern consistent
with core regions involved in autobiographical memory recall, including the
ventromedial PFC, anterior medial (am)PFC, inferior frontal gyrus, the posterior
cingulate cortex, the tempoparietal junction, the middle temporal gyrus and the
hippocampus. Further, we analyzed brain activation during AM retrieval after
hydrocortisone compared to placebo. Region of interest (ROI) analyses revealed a
hydrocortisone-induced deactivation during AM retrieval in the right amPFC.
Results of the ROI analyses were non-significant in the left and right
hippocampus, the left and right vmPFC and the left amPFC In sum, during AM
retrieval hydrocortisone had the most pronounced effects on the amPFC. This might
be explained by the strong involvement of this brain region in self-referential
behavior, which is essential for recalling autobiographic information.
PMID- 29940262
TI - The relationship between cavum septum pellucidum and psychopathic traits in
female offenders.
AB - Cavum Septum Pellucidum (CSP) is a common anatomical variant of the septum
pellucidum. CSP is considered a marker for abnormal limbic brain development, but
its functional consequences are non-specific. In a recent report (Crooks et al.,
2018), CSP size was significantly positively correlated with the
affective/interpersonal traits of psychopathy in male offenders (N = 1742). Here
we test the hypothesis that CSP is related to psychopathic traits in incarcerated
females (N = 355). We examine continuous relationships as well as categorical
assignments for CSP size corresponding to a number of prior reports. We also
compare female offenders to healthy female controls (N = 385). Consistent with
our reported findings in males, a positive association was observed between the
interpersonal psychopathic traits and CSP size. In contrast to findings among
males, an association between CSP and antisocial psychopathic traits was apparent
in females. There was no significant difference in CSP size (in mm) or CSP
presence/absence between incarcerated and non-incarcarated groups. However,
categorical rates of medium and large CSP were more common in female inmates than
in controls. This is the first systematic investigation of these variables in a
female inmate sample. In combination with our prior study, these findings
demonstrate that limbic abnormalities, as indexed by CSP, are related to
psychopathic traits in both female and male inmates.
PMID- 29940263
TI - Discovering hidden knowledge through auditing clinical diagnostic knowledge
bases.
AB - OBJECTIVE: Evaluate potential for data mining auditing techniques to identify
hidden concepts in diagnostic knowledge bases (KB). Improving completeness
enhances KB applications such as differential diagnosis and patient case
simulation. MATERIALS AND METHODS: Authors used unsupervised (Pearson's
correlation - PC, Kendall's correlation - KC, and a heuristic algorithm - HA)
methods to identify existing and discover new finding-finding interrelationships
("properties") in the INTERNIST-1/QMR KB. Authors estimated KB maintenance
efficiency gains (effort reduction) of the approaches. RESULTS: The methods
discovered new properties at 95% CI rates of [0.1%, 5.4%] (PC), [2.8%, 12.5%]
(KC), and [5.6%, 18.8%] (HA). Estimated manual effort reduction for HA-assisted
determination of new properties was approximately 50-fold. CONCLUSION: Data
mining can provide an efficient supplement to ensuring the completeness of
finding-finding interdependencies in diagnostic knowledge bases. Authors'
findings should be applicable to other diagnostic systems that record finding
frequencies within diseases (e.g., DXplain, ISABEL).
PMID- 29940264
TI - A subperiosteal maxillary implant causing severe osteolysis.
AB - Subperiosteal implant denture therapy was initially introduced in 1942 in Sweden
and was subsequently used worldwide for the treatment of fully edentulous
maxillary or mandibular arches with advanced bone atrophy. Most authors describe
decent success rates for mandibular subperiosteal implants in cases with major
bone atrophy but follow-up studies for maxillary subperiosteal implants are not
available. Here, we report a case of severe maxillary osteolysis secondary to the
placement of a subperiosteal in-house implant. Subperiosteal implants are rarely
used today but patients still carrying these devices can be challenging to manage
when severe complications occur. New technical advances, including the use of
surgical planification and additive manufacturing, may lead to a new interest in
subperiosteal implants.
PMID- 29940265
TI - Is submental flap safe for the oncological reconstruction of the oral cavity?
AB - AIM: The reconstruction of oral defects after oncological surgery is not an easy
task for head and neck surgeons. The main aim of this work is to evaluate the
functionality, viability and safety of submental flap for oral reconstruction.
MATERIALS AND METHOD: We analyzed the records of patients diagnosed with oral and
oropharyngeal SCC and reconstructed with the use of submental flap in Virgen de
las Nieves University Hospital of Granada (Spain) from 2014 and 2015. Nine
patients were found. Specific features such as age, sites of occurrence, sex
distribution, T stage at diagnosis, nodal involvement, functionality of
reconstruction and local and regional failure were determined. RESULTS: The
male/female ratio was 8:1. The average age of the patients was 59.6 years (range:
42-75). Tumor locations were base of the tongue (n2), lateral edge of the tongue
(n4), floor of the mouth (n2) and buccal mucosa (n1). Six tumors were classified
as a T2 tumor and 3 as T3. No major complications were evidenced during the
immediate postoperative period. Moreover, all patients showed excellent tissue
coverage with acceptable aesthetic and functional outcomes. However, 1 patient
showed partial epithelial loss of the skin paleta. Finally, the recurrence rate
of disease was 44,4%. Four of 9 patients experienced a local (1/9) or cervical
relapse (3/9). DISCUSSION: Submental flap might offer great aesthetic and
functional results in oral reconstruction. However, the recurrence rate of
disease was too high in our sample. From our point of view, submental flap should
be carefully indicated in oncological reconstruction, especially in case of
suspicion of lymph node involvement at level Ib.
PMID- 29940266
TI - Acute effects of high-intensity interval, resistance or combined exercise
protocols on testosterone - cortisol responses in inactive overweight
individuals.
AB - The purpose of this study was to compare the hormonal responses to one session of
high-intensity interval training (HIIT, 4 * 4 min intervals at 85-95% maximum
heart rate [HRmax], interspersed with 4 min of recovery at 75-85% HRmax),
resistance training (RT at 50-70% of one repetition maximum 12-15 repetitions per
set with 60s of recovery) or both (HIIT+RT) exercise protocol in a cohort of
physical inactivity, overweight adults (age 18-30 years old). Randomized,
parallel-group clinical trial among fifty-one men (23.6 +/- 3.5 yr; 83.5 +/- 7.8
kg; 28.0 +/- 1.9 kg/m2), physical inactivity (i.e., <150 min of moderate
intensity exercise per week for >6 months), with abdominal obesity (waist
circumference >=90 cm) or body mass index >=25 and <=30 kg/m2 were randomized to
the following 4 groups: high-intensity interval training (HIIT, n = 14),
resistance training (RT, n = 12), combined high-intensity interval and resistance
training (HIIT+RT, n = 13), or non-exercising control (CON, n = 12). Cortisol,
total- and free-testosterone and total-testosterone/cortisol-ratio (T/C)
assessments (all in serum) were determined before (pre) and 1-min post-exercise
for each protocol session. Decreases in cortisol levels were -57.08 (95%CI,
75.58 to -38.58; P = 0.001; n2 = 0.61) and - 37.65 (95%CI, -54.36 to -20.93; P =
0.001; n2 = 0.51) in the HIIT and control group, respectively. Increases in T/C
ratio were 0.022 (95%CI, 0.012 to 0.031; P = 0.001; n2 = 0.49) and 0.015 (95%CI,
0.004 to 0.025; P = 0.007; n2 = 0.29) in the HIIT and control group,
respectively. In per-protocol analyses revealed a significant change in cortisol
levels [interaction effect F(7.777), n2 = 0.33] and T/C ratio [interaction effect
F(5.298), n2 = 0.25] between groups over time. Additionally, we showed that in
both the intention-to-treat (ITT) and per protocol analyses, HIIT+RT did not
change serum cortisol, total or free testosterone. The present data indicate a
HIIT reduced cortisol and increased total-testosterone/cortisol-ratio levels
significantly in physically inactive adults. Further study is required to
determine the biological importance of these changes in hormonal responses in
overweight men.
PMID- 29940267
TI - Mice harboring a Hajdu Cheney Syndrome mutation are sensitized to osteoarthritis.
AB - Osteoarthritis is a joint disease characterized by cartilage degradation, altered
gene expression and inflammation. NOTCH1 and NOTCH2 receptors and the JAGGED1
ligand regulate chondrocyte biology; however, the contribution of Notch signaling
to osteoarthritis is controversial. Hajdu Cheney Syndrome (HCS) is a rare genetic
disorder affecting the skeleton and associated with NOTCH2 mutations that lead to
NOTCH2 gain-of-function. A murine model of the disease (Notch2tm1.1Ecan) was used
to test whether the HCS mutation increases the susceptibility to osteoarthritis.
The knee of three-month-old Notch2tm1.1Ecan male mice and control sex-matched
littermates was destabilized by resection of the medial meniscotibial ligament,
and changes in the joint analyzed two months thereafter. Expression of Notch
target genes was increased in the femoral heads of Notch2tm1.1Ecan mice,
documenting Notch signal activation. Periarticular bone and cartilage structures
were unaffected in Notch2tm1.1Ecan mutants subjected to sham surgery, indicating
that NOTCH2 gain-of-function had no discernible impact on joint structure under
basal conditions. However, destabilization of the medial meniscus increased
osteophyte volume and thickened subchondral bone in Notch2tm1.1Ecan mice compared
to wild type littermates. Moreover, destabilized Notch2tm1.1Ecan mutants
exhibited histological signs of moderate to severe cartilage degeneration,
demonstrating joint sensitization to the development of osteoarthritis.
Chondrocyte cultures from Notch2tm1.1Ecan mutants expressed increased Il6 mRNA
levels following exposure to JAGGED1, possibly explaining the susceptibility of
Notch2tm1.1Ecan mice to osteoarthritis. In conclusion, Notch2tm1.1Ecan mutants
are sensitized to the development of osteoarthritis in destabilized joints and
NOTCH2 activation may play a role in the pathogenesis of the disease.
PMID- 29940268
TI - Impact of DAAs on liver transplantation: Major effects on the evolution of
indications and results. An ELITA study based on the ELTR registry.
AB - BACKGROUND & AIMS: Direct-acting antivirals (DAAs) have dramatically improved the
outcome of patients with hepatitis C virus (HCV) infection including those with
decompensated cirrhosis (DC). We analyzed the evolution of indications and
results of liver transplantation (LT) in the past 10 years in Europe, focusing on
the changes induced by the advent of DAAs. METHODS: This is a cohort study based
on data from the European Liver Transplant Registry (ELTR). Data of adult LTs
performed between January 2007 to June 2017 for HCV, hepatitis B virus (HBV),
alcohol (EtOH) and non-alcoholic steatohepatitis (NASH) were analyzed. The period
was divided into different eras: interferon (IFN/RBV; 2007-2010), protease
inhibitor (PI; 2011-2013) and second generation DAA (DAA; 2014-June 2017).
RESULTS: Out of a total number of 60,527 LTs, 36,382 were performed in patients
with HCV, HBV, EtOH and NASH. The percentage of LTs due to HCV-related liver
disease varied significantly over time (p <0.0001), decreasing from 22.8% in the
IFN/RBV era to 17.4% in the DAA era, while those performed for NASH increased
significantly (p <0.0001). In the DAA era, the percentage of LTs for HCV
decreased significantly (p <0.0001) from 21.1% (first semester 2014) to 10.6%
(first semester 2017). This decline was more evident in patients with DC (HCV-DC,
-58.0%) than in those with hepatocellular carcinoma (HCC) associated with HCV
(HCV-HCC, -41.2%). Conversely, three-year survival of LT recipients with HCV
related liver disease improved from 65.1% in the IFN/RBV era to 76.9% in the DAA
era, and is now comparable to the survival of recipients with HBV infection (p =
0.3807). CONCLUSIONS: In Europe, the number of LTs due to HCV infection is
rapidly declining for both HCV-DC and HCV-HCC indications and post-LT survival
has dramatically improved over the last three years. This is the first
comprehensive study of the overall impact of DAA treatment for HCV on liver
transplantation in Europe. LAY SUMMARY: After the advent of direct-acting
antivirals in 2014, a dramatic decline was observed in the number of liver
transplants performed both in patients with decompensated cirrhosis due to
hepatitis C virus (HCV), minus 60%, and in those with hepatocellular carcinoma
associated with HCV, minus 41%. Furthermore, this is the first large-scale study
demonstrating that the survival of liver transplant recipients with HCV-related
liver disease has dramatically improved over the last three years and is now
comparable to the survival of recipients with hepatitis B virus infection. The
reduction in HCV-related indications for LT means that there is a greater
availability of livers, at least 600 every year, which can be allocated to
patients with indications other than HCV.
PMID- 29940269
TI - Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic
fatty liver disease.
AB - The global epidemic of obesity has been accompanied by a rising burden of non
alcoholic fatty liver disease (NAFLD), with manifestations ranging from simple
steatosis to non-alcoholic steatohepatitis, potentially developing into
hepatocellular carcinoma. Although much attention has focused on NAFLD, its
pathogenesis remains largely obscure. The hallmark of NAFLD is the hepatic
accumulation of lipids, which subsequently leads to cellular stress and hepatic
injury, eventually resulting in chronic liver disease. Abnormal lipid
accumulation often coincides with insulin resistance in steatotic livers and is
associated with perturbed endoplasmic reticulum (ER) proteostasis in hepatocytes.
In response to chronic ER stress, an adaptive signalling pathway known as the
unfolded protein response is triggered to restore ER proteostasis. However, the
unfolded protein response can cause inflammation, inflammasome activation and, in
the case of non-resolvable ER stress, the death of hepatocytes. Experimental data
suggest that the unfolded protein response influences hepatic tumour development,
aggressiveness and response to treatment, offering novel therapeutic avenues.
Herein, we provide an overview of the evidence linking ER stress to NAFLD and
discuss possible points of intervention.
PMID- 29940270
TI - MicroRNA-216a promotes M1 macrophages polarization and atherosclerosis
progression by activating telomerase via the Smad3/NF-kappaB pathway.
AB - Macrophages exhibit heterogeneity and plasticity and imbalance between pro
inflammatory and anti-inflammatory macrophages plays a critical role in
atherosclerosis progression. Telomerase reverse transcriptase (TERT) in
macrophages can be activated by nuclear factor-kappa B (NF-kappaB), but the
regulation of telomerase activation on macrophages polarization remains unknown.
We previously identified microRNA-216a (miR-216a) to promote inflammation through
directly targeting the Smad3/NF-kappaB pathway. The present study aimed to assess
whether miR-216a can regulate telomerase activity and promote macrophages
polarization during atherosclerosis progression. The results verified that TERT
was highly expressed in macrophages of human carotid atherosclerotic plaques. miR
216a was found to promote telomerase activation in macrophages by 4.5-fold (P =
0.002) through the Smad3/NF-kappaB pathway. miR-216a also induced macrophages
senescence characterized by senescence-associated-beta-galactosidase activity and
p53 and p16 expression. TERT overexpression promoted the transformation of M2 to
M1 while this conversion was suppressed once TERT was inhibited, and the related
inflammatory factors and lipid uptake ability of M1 cells were also increased by
TERT. In the carotid atherosclerotic plaques from miR-216a-treated apolipoprotein
E-/- mice, the numbers of M1 macrophages were increased whereas M2 cells reduced,
accompanying with inhibited Smad3 expression and upregulated inflammatory markers
and TERT activity. Furthermore, plasma miR-216a level was specifically higher in
patients with vulnerable mixed plaques (n = 181) than those with calcified
plaques (n = 73) and controls (n = 264). In summary, our findings first revealed
a new molecular mechanism of macrophage polarization involving telomerase
activation induced by miR-216a through the Smad3/NF-kappaB signaling, which might
serve as a potential therapeutic target for atherosclerosis progression.
PMID- 29940271
TI - Preface - Animal models for aging.
PMID- 29940272
TI - Evolutionary progression of mitochondrial gene rearrangements and phylogenetic
relationships in Strigidae (Strigiformes).
AB - The bird mitogenome is generally considered to have a conservative genome size,
consistent gene content, and similar gene order. As more mitogenomes are
sequenced, mitochondrial (mt) gene rearrangements have been frequently identified
among diverse birds. Within two genera (Bubo and Strix) of typical owls
(Strigidae, Strigiformes), the rearrangement of the mt gene has been a subject of
debate. In the current study, we first sequenced the whole mitogenomes of S.
uralensis and B. scandiaca and resequenced the entire mitogenome of B. bubo. By
combining our data with previously sequenced mitogenomes in Strigidae, we
examined the mt gene rearrangements in the family and attempted to reconstruct
the evolutionary progression of these rearrangements. The mitogenomes were then
used to review the phylogenies of Strigidae. Most mitogenomes exhibited the
ancestral gene order (A) in Strigidae. The ancestral gene order in the previously
published mitogenome of B. bubo was found to be incorrect. We determined the mt
gene order (the duplicate tRNAThr-CR, B) and discovered two additional mt gene
orders (the duplicate tRNAGlu-L-CR and CR, C and D) in the Bubo and Strix genera.
Gene order B was likely derived from A by a tandem duplication of the region
spanning from tRNAThr to CR. The other two modified gene orders, C and D, were
likely derived from B by further degenerations or deletions of one copy of
specific duplicated genes. We also preliminarily reconstructed the evolutionary
progression of mt gene rearrangements and discussed maintenance of the duplicated
CR in the genera. Additionally, the phylogenetic trees based on the mitogenomes
supported the division of Strigidae into three subfamilies: Ninoxinae +
(Surniinae + Striginae). Within the Striginae clade, the four genera formed a
phylogenetic relationship: Otus + (Asio + (Bubo + Strix)). This suggests that
Otus firstly diverges in their evolutionary history, and Bubo and Strix show a
close relationship. B. bubo, B. blakistoni and B. scandiaca form a clade should
be considered members of the same genus. The well-supported topology obtained in
our Bayesian inference (BI) and maximum likelihood (ML) analyses of Strigid
mitogenomes suggests that these genomes are informative for constructing
phylogenetic relationships.
PMID- 29940273
TI - Developmental characterization and environmental stress responses of Y-box
binding protein 1 gene (AccYB-1) from Apis cerana cerana.
AB - Y-box binding protein 1 (YB-1) is a member of the cold shock domain protein
superfamily and is involved in development, environmental stresses and DNA
oxidative damage in many organisms. However, the precise functions of YB-1 are
still not well understood in various insects, including bees. In the current
study, we identified a YB-1 gene in Apis cerana cerana (AccYB-1). The predicted
cis-acting elements in the promoter sequence of AccYB-1 indicated its possible
roles in development and stress responses. AccYB-1 expression was higher in one
day-old larvae and dark-eyed pupae than in other development stages. Tissue
specific expression analysis showed that the mRNA level of AccYB-1 was higher in
the thorax and midgut than in other tissues. The results from real-time PCR
showed that AccYB-1 was induced by many environmental stresses. Silencing AccYB-1
downregulated the transcriptional level of some growth- and development-related
genes and antioxidant genes and decreased the enzyme activities of several
antioxidant-related enzymes, further indicating a possible function of AccYB-1 in
growth, development and stress responses. Taken together, our findings suggest
that AccYB-1 may play an indispensable role in growth and development and
environmental stress responses in Apis cerana cerana. To our knowledge, this is
the first paper to explore the role of YB-1 in bees.
PMID- 29940274
TI - Molecular characterization and expression of NLRP10 in the antibacterial host
defense of the sea cucumber (Apostichopus japonicus).
AB - The nucleotide-binding oligomerization domain-like receptors (NOD-like receptors,
NLRs) can regulate the innate immune process and is an important part of
inflammatory body. In this study, we use transcriptome sequencing and the rapid
amplification of cDNA ends approach to identify a novel NLRP gene in Apostichopus
japonicus. We designated the gene as AjNLRP10. The full-length of AjNLRP10 is
4509 bp. The putative open reading frame comprising 3489 bp encodes a polypeptide
with 1162 amino acid residues. The predicted molecular mass of AjNLRP10 is 132.87
kDa and its theoretical pI is 5.60. AjNLRP10 comprises a signal peptide with two
Ig superfamily (IgSF) domains and a NACHT [NAIP (neuronal apoptosis inhibitory
protein), CIITA (MHC class II transcription activator), HET-E (incompatibility
locus protein from Podospora anserina) and TP1 (telomerase-associated protein)]
domain. Spatial distribution expression analysis detected AjNLRP10 in all of the
tissues tested, but with higher expression in the coelomocytes, medium expression
in the intestine and respiratory tree, and slightly weaker expression in the body
wall, tube feet, and longitudinal muscle. The expression levels of AjNLRP10 in
the respiratory tree and intestines of sea cucumbers with skin ulceration
syndrome were increased by 4-fold and 2.7-fold compared with those in healthy sea
cucumbers, respectively. We investigated expression profiles of AjCasepase-1
(Cysteinyl aspartate specific proteinase-1) and AjMMP37 (mitochondrial protein
37) after AjNLRP10 knock-down and discovered that AjCasepase-1 was raised by 2.60
fold and AjMMP37 was raised by 3.84-fold. The study showed that AjNLRP10 has
inhibitory effect in the immune process. In conclusion, this study showed that
the AjNLRP10 protein found in the sea cucumber involved with the innate immune
responses against bacterial infection. It has a similar structure and biological
function to that in other organisms, where it appears to be involved with these
results provide insights into the innate immune mechanism in the sea cucumber as
well as suggesting new strategies for disease prevention, molecular therapy, and
the development of novel drugs for sea cucumbers.
PMID- 29940275
TI - Correlations of PD-L1 gene polymorphisms with susceptibility and prognosis in
hepatocellular carcinoma in a Chinese Han population.
AB - AIMS: This study was performed to investigate the effect of PD-L1 polymorphisms
on the susceptibility and prognosis of hepatocellular carcinoma (HCC) in a
Chinese Han population. METHODS: Four single nucleotide polymorphisms (SNPs) of
the PD-L1 gene, including rs2297136 (C > T), rs4143815 (C > G), rs2890658 (A > C)
and rs17718883 (C > G) were examined in 225 HCC patients and 200 healthy controls
using polymerase chain reaction restriction fragment length polymorphism (PCR
RFLP) method. RESULTS: Data revealed that the rs2297136 (C > T) SNP TT (p = 0.03)
and rs4143815 (C > G) SNP GG genotypes (p < 0.001) were associated with
significantly increased risks of HCC. No association was found between rs2890658
(A > C) SNP and HCC risk and this risk was significantly decreased in individuals
with the rs17718883 SNP CG + GG genotype (p < 0.001). The rs2297136 (C > T) SNP
CC + CT genotypes, the rs4143815 (C > G) CC genotype and the rs2890658 (A > C) AA
genotype were associated with increased overall survival compared to their
counterpart allelic genotypes (p < 0.001). The rs2890658 (A > C) SNP had no
impact on the risk and prognosis of HCC (p > 0.05). CONCLUSIONS: Our results
indicated that three functional polymorphisms (rs2297136, rs4143815 and
rs17718883) of the PD-L1 gene were associated with HCC risk and prognosis,
suggesting that genetic variants of PD-L1 polymorphisms might be a possible
prognostic marker for the prediction of HCC risk and development. Validation by a
larger prospective study from a more diverse ethnic population is needed to
confirm these findings.
PMID- 29940276
TI - Association between IFITM3 rs12252 polymorphism and influenza susceptibility and
severity: A meta-analysis.
AB - Intrinsic host susceptibility to viral infections plays a major role in
determining infection severity in different individuals. In human influenza virus
infections, multiple genetic association studies have identified specific human
gene variants that might contribute to enhanced susceptibility or resistance to
influenza. Recent studies suggested, the rs12252 T > C polymorphism in the
interferon-inducible transmembrane protein 3 (IFITM3) gene might be associated
with susceptibility to severe influenza. However, the studies reported
conflicting and inconclusive results. To resolve the controversy, we conducted a
systematic meta-analysis to evaluate the role of the IFITM3 rs12252 polymorphism
in influenza susceptibility and severity, including twelve studies published
before February 19, 2018 with a total 16,263 subjects (1836 influenza cases and
14,427 controls). Odds ratios (OR) and 95% confidence intervals were used to
assess the strength of the association. Our results indicated increased risk of
both severe and mild influenza in subjects carrying the IFITM3 rs12252
polymorphism in the allele contrast C vs. T: OR (severe) = 1.69, 95% CI = 1.23
2.33, P = 0.001, and OR (mild) = 1.46, 95% CI = 1.13-1.87, P = 0.004. Similar
results were obtained in the homozygote comparison and dominant model. Stratified
analyses by ethnicity revealed increased risk of severe influenza in both the
White and East Asian populations, but significant association with mild influenza
was found only in the White population. Overall, our meta-analysis suggests a
significant association between the IFITM3 rs12252 polymorphism and the risk of
influenza in both the White and East Asian populations.
PMID- 29940277
TI - Notch signaling in the division of germ layers in bilaterian embryos.
AB - Bilaterian embryos are triploblastic organisms which develop three complete germ
layers (ectoderm, mesoderm, and endoderm). While the ectoderm develops mainly
from the animal hemisphere, there is diversity in the location from where the
endoderm and the mesoderm arise in relation to the animal-vegetal axis, ranging
from endoderm being specified between the ectoderm and mesoderm in echinoderms,
and the mesoderm being specified between the ectoderm and the endoderm in
vertebrates. A common feature is that part of the mesoderm segregates from an
ancient bipotential endomesodermal domain. The process of segregation is noisy
during the initial steps but it is gradually refined. In this review, we discuss
the role of the Notch pathway in the establishment and refinement of boundaries
between germ layers in bilaterians, with special focus on its interaction with
the Wnt/beta-catenin pathway.
PMID- 29940278
TI - Stabilization of G-quadruplex structure on vascular endothelial growth factor
gene promoter depends on CpG methylation site and cation type.
AB - BACKGROUND: DNA methylation at the 5-position of cytosine is an epigenetic
modification of CpG dinucleotides. In addition to CpG methylation, the G
quadruplex (G4) structure has been reported as a regulator of gene expression.
The identification of G4 forming sequences in CpG islands suggests an involvement
of CpG-methylated G4 structures in biological processes; however, few reports
have addressed the effects of CpG methylation on G4 structure. METHODS: The
thermostability of a methylated, 21-mer G4 structure located on the vascular
endothelial growth factor (VEGF) gene promoter containing four CpG sites (C1, C6,
C11, and C17) were investigated using circular dichroism (CD) spectral analysis.
RESULTS: CD melting analysis revealed that VEGF G4 was stabilized by a single CpG
methylation on C11 in the presence of Na+ and Mg2+. However, either C1 or C11
methylation enhanced VEGF G4 thermal stability in the presence of K+.
CONCLUSIONS: Single CpG methylation appears to enhance VEGF G4 thermostability in
a manner dependent on both the CpG methylation site and cation type. GENERAL
SIGNIFICANCE: These results are expected to contribute to the elucidation of the
roles of CpG methylation-stabilized G4 structures in biological processes.
PMID- 29940280
TI - The role of cholesterol oxidation products in food toxicity.
AB - Food consumption can lead to the accumulation of certain chemical compounds able
to exert toxic activities against humans. Of mayor interests are those molecules
generated during food processing and handling, since their occurrence and
distribution depend of many intrinsic and extrinsic factors. Cholesterol - a
lipid constituent of mammalian cells - is the precursor of several toxic
molecules known as cholesterol oxidation products (COPs). In the last decades, it
has been demonstrated that food processing can dramatically trigger COPs
accumulation in meats, eggs, dairy products, fish and poultry. On the other hand,
countless scientific evidences have pointed out the highly toxic and pathogenic
activities of COPs, from cancer stimulation to neurodegenerative disorders, via
molecular mechanisms that are largely unexplored. The aim of this review is to
merge the evidence on COPs accumulation in foods and their toxic activities
through dietary intake, as from in vivo and in vitro studies. We consider that it
is imperative to systematically monitor the formation of COPs to bridge these
quantitative efforts with a risk exposure assessment on sensitive populations.
PMID- 29940279
TI - RIFM FRAGRANCE INGREDIENT SAFETY ASSESSMENT, 2,6-Dimethylocta-2,4,6-triene, CAS
Registry Number 673-84-7.
PMID- 29940282
TI - Detailed somatotopy in primary motor and somatosensory cortex revealed by
Gaussian population receptive fields.
AB - The relevance of human primary motor cortex (M1) for motor actions has long been
established. However, it is still unknown how motor actions are represented, and
whether M1 contains an ordered somatotopy at the mesoscopic level. In the current
study we show that a detailed within-limb somatotopy can be obtained in M1 during
finger movements using Gaussian population Receptive Field (pRF) models. Similar
organizations were also obtained for primary somatosensory cortex (S1), showing
that individual finger representations are interconnected throughout sensorimotor
cortex. The current study additionally estimates receptive field sizes of
neuronal populations, showing differences between finger digit representations,
between M1 and S1, and additionally between finger digit flexion and extension.
Using the Gaussian pRF approach, the detailed somatotopic organization of M1 can
be obtained including underlying characteristics, allowing for the in-depth
investigation of cortical motor representation and sensorimotor integration.
PMID- 29940281
TI - RIFM fragrance ingredient safety assessment, 1-oxaspiro[4.5]decan-2-one, 8-methyl
, CAS Registry Number 94201-19-1.
PMID- 29940283
TI - Implicit reward associations impact face processing: Time-resolved evidence from
event-related brain potentials and pupil dilations.
AB - The present study aimed at investigating whether associated motivational salience
causes preferential processing of inherently neutral faces similar to emotional
expressions by means of event-related brain potentials (ERPs) and changes of the
pupil size. To this aim, neutral faces were implicitly associated with monetary
outcome, while participants (N = 44) performed a face-matching task with masked
primes that ensured performance around chance level and thus an equal proportion
of gain, loss, and zero outcomes. During learning, motivational context strongly
impacted the processing of the fixation, prime and mask stimuli prior to the
target face, indicated by enhanced amplitudes of subsequent ERP components and
increased pupil size. In a separate test session, previously associated faces as
well as novel faces with emotional expressions were presented within the same
task but without motivational context and performance feedback. Most importantly,
previously gain-associated faces amplified the LPC, although the individually
contingent face-outcome assignments were not made explicit during the learning
session. Emotional expressions impacted the N170 and EPN components. Modulations
of the pupil size were absent in both motivationally-associated and emotional
conditions. Our findings demonstrate that neural representations of neutral
stimuli can acquire increased salience via implicit learning, with an advantage
for gain over loss associations.
PMID- 29940284
TI - Novel insights from the Yellow Light Game: Safe and risky decisions
differentially impact adolescent outcome-related brain function.
AB - Changes across the span of adolescence in the adolescent reward system are
thought to increase the tendency to take risks. While developmental differences
in decision and outcome-related reward processes have been studied extensively,
existing paradigms have largely neglected to measure how different types of
decisions modulate reward-related outcome processes. We modified an existing
decision-making paradigm (the Stoplight Task; Chein et al., 2011) to create a
flexible laboratory measure of decision-making and outcome processing, including
the ability to assess modulatory effects of safe versus risky decisions on reward
related outcome processes: the Yellow Light Game (YLG). We administered the YLG
in the MRI scanner to 81 adolescents, ages 11-17 years, recruited from the
community. Results showed that nucleus accumbens activation was enhanced for (1)
risky > safe decisions, (2) positive > negative outcomes, and (3) outcomes
following safe decisions compared to outcomes following risky decisions,
regardless of whether these outcomes were positive or negative. Outcomes
following risky decisions (compared to outcomes following safe decisions) were
associated with enhanced activity in cortical midline structures. Furthermore,
while there were no developmental differences in risk-taking behavior, more
pubertally mature adolescents showed enhanced nucleus accumbens activation during
positive > negative outcomes. These findings suggest that outcome processing is
modulated by the types of decisions made by adolescents and highlight the
importance of investigating processes involved in safe as well as risky decisions
to better understand the adolescent tendency to take risks.
PMID- 29940285
TI - Does ezrin play a predictive role in cancer patients undergoing radiotherapy
and/or chemotherapy?
PMID- 29940286
TI - Overexpression of signal sequence receptor gamma predicts poor survival in
patients with hepatocellular carcinoma.
AB - SSR subunit gamma (SSR3), an SSR family member, is heavily involved in cell
growth and differentiation and closely associated with many tumor types. However,
the role of this protein in HCC remains unknown. In this study, we used data from
public databases to analyze SSR3 expression in HCC. We subjected 20 pairs of
fresh-frozen tissues to quantitative real-time polymerase chain reaction to
investigate SSR3 expression. We also subjected 95 formalin-fixed, paraffin
embedded HCC tissues to immunohistochemistry to detect SSR3 expression and
determine the clinical significance of SSR3 expression in HCC. Bioinformatics
analysis and quantitative real-time polymerase chain reaction results showed that
compared with that in adjacent normal liver tissues, SSR3 was highly expressed in
HCC tissues. High SSR3 expression was positively correlated with tumor size (P <
.01), cancer embolus (P = .01), TNM stages (P = .02), and differentiation grades
(P < .01). Kaplan-Meier and Cox proportional hazards analyses indicated that high
SSR3 expression was significantly associated with poor survival in HCC patients
and that SSR3 was an independent prognostic factor for overall survival in HCC
patients. In conclusion, SSR3 acts as an oncogene in HCC and can therefore serve
as a biomarker for the prognoses of HCC patients.
PMID- 29940287
TI - SASH1, a potential therapeutic target for cancer-reply.
PMID- 29940288
TI - Utility of STAT6 and 13q14 deletion in the classification of the benign spindle
cell stromal tumors of the breast.
AB - The boundaries of the benign spindle cell stromal tumors of the breast are still
confusing. This is the reason why different names are interchangeably used for
the same tumor and vice versa the same name for different tumors. Therefore, we
studied the immunoexpression of easily available markers, such as CD34, alpha
smooth muscle actin, and desmin, with the addition of STAT6, as well as the
chromosome 13q14 region by fluorescence in situ hybridization analysis in a
series of 19 cases of benign spindle cell stromal tumors of the breast. Based on
the morphologic and immunohistochemical findings, the following histotypes were
identified: (i) tumors (10/19 cases) with the characteristic morphology of
myofibroblastoma and stained with vimentin, CD34, desmin, and alpha-smooth muscle
actin; (ii) fibroblastic benign spindle cell tumors (5/19 cases) composed of
fibroblast-like cells stained only with vimentin and CD34; (iii) tumors (2/19
cases) with the typical morphologic features of solitary fibrous tumor and
stained with vimentin, CD34, and STAT6; (iv) 1 case of spindle cell lipoma
stained with vimentin and CD34; and (v) 1 case of fibroma composed of a
paucicellular, diffusely hyalinized stroma with expression of vimentin and CD34.
Notably most of the tumors, with the exception of solitary fibrous tumor, showed
monoallelic deletion of FOXO1. This finding supports that myofibroblastoma,
fibroblastic benign spindle cell tumor, spindle cell lipoma, and fibroma of the
breast are histogenetically related lesions which belong to the same tumor
entity.
PMID- 29940289
TI - Impact of toothbrushing frequency and toothpaste fluoride/abrasivity levels on
incipient artificial caries lesion abrasion.
AB - OBJECTIVES: To investigate the interplay among brushing frequency, dentifrice
slurry abrasivity, and fluoride content on the surface loss (SL) of incipient
enamel caries-like lesions. METHODS: Lesions were created in 96 bovine enamel
specimens (5 * 5 mm) using methylcellulose acid gel. Specimens were randomly
allocated to 12 groups (n = 8), resulting from the association of three
experimental factors: (1) slurry abrasive level [low: REA = 4/RDA = 69 and high:
REA = 7/RDA = 208], (2) fluoride concentration [275 and 1250 ppm F as NaF], and
(3) brushing frequency [1, 2 and 3* daily]. Specimens were kept in artificial
saliva in between brushings and overnight. SL was determined by optical
profilometry after lesion creation, 1, 3, 5, and 7 days. Data was analyzed with
repeated measures ANOVA and Tukey's tests (alpha = 0.05). RESULTS: High abrasive
slurry caused significantly more SL than low with 275 ppm (p < 0.001) but not
with 1250 ppm fluoride (p = 0.34). Fluoride at 275 ppm had significantly more SL
than 1250 ppm with high abrasive slurry after 7 days (p = 0.008). Brushing 1*/day
had significantly less SL than 3*/day after 7 days with high abrasive slurry (p =
0.016), especially in the 275 ppm fluoride groups. CONCLUSIONS: Higher fluoride
concentration increased protection against the deleterious effect of high
abrasive slurry. SL was higher if brushing was performed more than twice daily
especially in low fluoride groups. CLINICAL SIGNIFICANCE: Highly abrasive
toothpaste formulations might cause more surface wear to incipient caries
lesions, especially at higher brushing frequencies. Increasing the fluoride
content may be beneficial at these circumstances.
PMID- 29940290
TI - Relationship between noncarious cervical lesions, cervical dentin
hypersensitivity, gingival recession, and associated risk factors: A cross
sectional study.
AB - OBJECTIVES: The aim of this study was to evaluate the risk factors associated
with noncarious cervical lesions (NCCLs), cervical dentin hypersensitivity (CDH),
and gingival recession (GR), besides the relationship among these conditions in a
specific Brazilian sample population. METHODS: 185 patients who attended the
"Ambulatory Program for Rehabilitation of Patients with Noncarious Cervical
Lesions and Cervical Dentin Hypersensitivity" were evaluated, and 5180 teeth were
analyzed. The subjects filled out a form and a calibrated examiner performed the
clinical exams to determine the presence of NCCLs, CDH, and GR. NCCLs were
classified according to their morphology and depth, CDH levels were evaluated
according to air stimuli response, and GRs were categorized according to Miller's
classification. The association of the risk factors with NCCLs, CDH, and GR was
determined with the Mann-Whitney U test and multiple linear regression. For the
correlations, the Spearman test was used with a 95%-confidence level. RESULTS:
The NCCLs, CDH, and GR distributions within the study were 88.1%, 89.1%, and
59.4%, respectively. Maxillary premolars were the most affected by all three
conditions. A positive correlation was found between age, NCCLs, and GR; between
NCCLs and CDH; CDH and GR; GR and NCCLs. Age, gender, oral hygiene,
gastroesophageal diseases, and occlusal trauma were significantly associated with
the presence of all three conditions. CONCLUSIONS: The NCCLs and GR distributions
increased with age; NCCLs, CDH, and GR had positive correlation; the lesions'
depth and morphology contributed to high levels of sensitivity and severity of
recessions; age, gender, gastric disease, and occlusal trauma were relevant
factors for the occurrence of NCCLs, CDH, and GR. CLINICAL SIGNIFICANCE: The
increasing distribution of NCCLs, CDH, and GR is closely associated with people's
lifestyles. Thus, it is important for the clinicians to recognize the etiological
factors and their most relevant associations to prevent and control such
alterations, in order to improve the population's quality of life.
PMID- 29940291
TI - Segmenting women eligible for cervical cancer screening using demographic,
behavioural and attitudinal characteristics.
AB - The best ways to communicate effectively to under-screened women about cervical
cancer screening are unknown. Segmentation techniques create homogeneous segments
of women in the population that are different from one another, and help to
determine on whom communication efforts should be focused and how messaging
should be tailored. We used segmentation techniques to better understand the
demographics, attitudes and behaviours of women eligible for cervical screening.
We developed a brief online questionnaire that consisted of demographic
characteristics, attitudes toward health, and cervical screening behaviour.
Simple descriptive statistics were used to describe the study population and
principal components analysis was used to define the segments. The study sample
consisted of 615 women living in Ontario, 508 from the general population and 107
from South Asia; 63.1% reported regular screening. We defined four segments that
represented the sample: i) Proactive, ii) Family First, iii) Social and Stylish,
and iv) Faith-Driven. South Asians were represented in all segments. Women who
were in the Family First and Faith-Driven segments were least likely to have
regular Pap tests and were least likely to know about human papilloma virus
(HPV)'s role in cervical cancer. The Internet was very popular among women in all
segments as a source of health information, particularly among Faith-Driven
women. Only 69.2% of Family First women listed their family physician as a source
of health information vs. 91.1% of Proactive women. Future research should focus
on how to most effectively reach women who meet the Family First and Faith-Driven
profiles, and through which communication media.
PMID- 29940292
TI - Effectiveness of a complex intervention on smoking in adolescents: A cluster
randomized controlled trial.
AB - : Tobacco smoking is a major preventable cause of death, and a significant public
health problem worldwide. Most smokers begin in adolescence, age at which they
are more susceptible to nicotine addiction. The prevalence of smoking in
adolescence is considerable. Therefore, it would be convenient to incorporate
smoking prevention programs in the school environment. It is necessary to provide
evidence of its effectiveness. The primary objective of the study was to evaluate
the effectiveness of a teacher-delivered school-based intervention on the
initiation of smoking in adolescents (ITACA smoking prevention education
program). A multi-center cluster randomized trial was designed. Twenty-two
secondary schools from Spain were enrolled in 2 successive cohorts, from 2010 to
2011. The intervention consisted in the application of the ITACA smoking
prevention education program. A 4-year cognitive-behavioral intervention that is
based on the social-influences model and is integrated into schools' regular
curricular activities. A total of 1055 students were surveyed before the
intervention (age: 12-13 years-old), and at the third year of the intervention
(age: 14-15 years-old) of a 4-year education program. The outcome measures were
daily and weekly use of cigarettes, and initiation of smoking. There was no
evidence that the intervention impacted the incidence of regular smoking (OR =
1.08; 95% CI: 0.50-2.33) or the initiation of smoking (OR = 1.09; 95% CI: 0.56
1.72). This trial provides evidence supporting the non-effectiveness of a complex
educational smoking prevention program at 3 years after the intervention. TRIAL
REGISTRATION NUMBER: Current Controlled Trials: NCT01602796.
PMID- 29940293
TI - Political orientation, political environment, and health behaviors in the United
States.
AB - Political orientation (Republican/Democrat and conservative/liberal) and
political environment (geo-spatial political party affiliated voting patterns)
are both associated with various health outcomes, including mortality. Modern
disease etiology in the U.S. suggests that many of our health outcomes derive
from behaviors and lifestyle choices. Thus, we examine the associations of
political orientation and political environment with health behaviors. We used
the Annenberg National Health Communication Survey (ANHCS) data, which is a
nationally representative U.S. survey fielded continuously from 2005 through
2012. The health behaviors studied include health information search, flu
vaccination, excessive alcohol consumption, tobacco consumption, exercise, and
dietary patterns. Democrats/liberals had higher odds of cigarette smoking and
excessive drinking compared to Republicans/conservatives. Whereas,
Republicans/conservatives ate fewer servings and fewer varieties of fruit and
vegetables; ate more high fat and processed foods; and engaged in less in-depth
health information searches compared to Democrats/liberals. Also, conservatives
had lower odds of exercise participation than liberals; whereas Republicans had
lower odds of flu vaccination. Greater Republican vote share in the 2008 and 2012
presidential elections at the state and/or county levels was associated with
higher odds of flu vaccination and smoking cigarettes and lower odds of avoiding
fat/calories, avoiding fast/processed food, eating a variety of fruits and
vegetables, and eating more servings of fruit. We use the distinct cognitive
motivational styles attributed to political orientation in discussing the
findings. Health communication strategies could leverage these relationships to
produce tailored and targeted messages as well as to develop and advocate for
policy.
PMID- 29940294
TI - A potential termination of resuscitation rule for EMS to implement in the field
for out-of-hospital cardiac arrest: An observational cohort study.
AB - INTRODUCTION: Despite international guidelines recommending termination of
resuscitation (TOR) rules for out-of-hospital cardiac arrest (OHCA), their
implementation remains low. We aimed to develop and validate a new TOR rule that
could allow emergency medical service (EMS) personnel to immediately and
objectively decide whether to withhold further resuscitation attempts after their
arrival. METHODS: This observational study evaluated data from OHCA cases in a
prospectively collected nationwide Utstein-style Japanese database (2008-2012).
Patients were divided into a development cohort (2008-2010, n = 342,055) and a
validation cohort (2011-2012, n = 247,283). A new TOR was developed based on
multivariable logistic regression analysis of factors that were associated with
unfavourable neurological outcomes. Validation was performed based on
specificity, the positive predictive value (PPV), and the area under the receiver
operating characteristic curve (AUC). RESULTS: Three factors were strongly
associated with unfavourable neurological outcomes at one month after OHCA:
unshockable initial rhythm (adjusted odds ratio [aOR]: 6.09, 95% confidence
interval [CI]: 5.81-6.38), unwitnessed by bystanders (aOR: 5.27, 95% CI: 4.99
5.57), and age of >=73 years (adjusted OR: 2.34, 95% CI: 2.24-2.45). In the
validation cohort, the new TOR rule provided specificity of 0.955 (95% CI: 0.950
0.959), a PPV of 0.996 (95% CI: 0.996-0.997), and an AUC of 0.828 (95% CI: 0.824
0.833). CONCLUSION: Based on three objective variables: unshockable initial
rhythm, unwitnessed by bystanders, and age >=73 years, which can be collected
immediately after the arrival of EMS personnel at the scene, a new TOR can be
developed. Our potential new TOR rule provided an excellent PPV (>99%) for
unfavourable neurological outcomes at one month after OHCA.
PMID- 29940295
TI - Overexpression of programmed cell death-1 and human leucocyte antigen-DR on
circulatory regulatory T cells in out-of-hospital cardiac arrest patients in the
early period after return of spontaneous circulation.
AB - AIM: Whether regulatory T cells (Tregs) are involved in immune disorders of out
of-hospital cardiac arrest (OHCA) patients after return of spontaneous
circulation (ROSC) is still unknown. We aimed to observe the expression of
circulatory Tregs in OHCA patients and investigate programmed cell death-1 (PD-1)
and human leucocyte antigen-DR (HLA-DR) on Tregs to evaluate the induction and
activity of Tregs. METHODS: Sixty-seven consecutive OHCA patients who recovered
from spontaneous circulation over 12 h were enrolled. Clinical and 28-day outcome
data were collected. Peripheral blood samples collected on days 1 and 3 after
ROSC were analysed to evaluate PD-1 and HLA-DR expression on Tregs. Fifty healthy
individuals were enrolled as healthy controls. RESULTS: Compared with those in
healthy individuals, circulatory Treg counts significantly decreased without
changes of Treg/cluster-of-differentiation (CD)4+ lymphocyte ratios on day 1
after ROSC, and the percentage of PD-1+ Tregs and HLA-DR+ Tregs significantly
rose. On day 3, Treg/CD4+ lymphocyte ratios rose with persistently low Treg
counts, and the expression of PD-1 and HLA-DR on Tregs was not different from
that on day 1. On day 1, both circulatory Treg counts and Treg/CD4+ lymphocyte
ratios in non-survivors were lower than those in survivors, and Treg/CD4+
lymphocyte ratios increased in non-survivors on day 3. No significant difference
of PD-1 and HLA-DR expression on Tregs was found between survivors and non
survivors on day 1. CONCLUSIONS: After ROSC, despite decreased circulatory Treg
counts, a relative increase of Treg percentage and enhanced activity of Tregs are
involved in early immune regulation of OHCA patients.
PMID- 29940296
TI - Arrest etiology among patients resuscitated from cardiac arrest.
AB - INTRODUCTION: Cardiac arrest etiology is often assigned according to the Utstein
template, which differentiates medical (formerly "presumed cardiac") from other
causes. These categories are poorly defined, contain within them many clinically
distinct etiologies, and are rarely based on diagnostic testing. Optimal clinical
care and research require more rigorous characterization of arrest etiology.
METHODS: We developed a novel system to classify arrest etiology using a
structured chart review of consecutive patients treated at a single center after
in- or out-of-hospital cardiac arrest over four years. Two reviewers
independently reviewed a random subset of 20% of cases to calculate inter-rater
reliability. We used X2 and Kruskal-Wallis tests to compare baseline clinical
characteristics and outcomes across etiologies. RESULTS: We identified 14
principal arrest etiologies, and developed objective diagnostic criteria for
each. Inter-rater reliability was high (kappa = 0.80). Median age of 986 included
patients was 60 years, 43% were female and 71% arrested out-of-hospital. The most
common etiology was respiratory failure (148 (15%)). A minority (255 (26%))
arrested due to cardiac causes. Only nine (1%) underwent a diagnostic workup that
was unrevealing of etiology. Rates of awakening and survival to hospital
discharge both differed across arrest etiologies, with survival ranging from 6%
to 60% (both P < 0.001), and rates of favorable outcome ranging from 0% to 40% (P
< 0.001). Timing and mechanism of death (e.g. multisystem organ failure or brain
death) also differed significantly across etiologies. CONCLUSIONS: Arrest
etiology was identifiable in the majority cases via systematic chart review.
"Cardiac" etiologies may be less common than previously thought. Substantial
clinical heterogeneity exists across etiologies, suggesting previous
classification systems may be insufficient.
PMID- 29940297
TI - Porous microspheres: Synthesis, characterisation and applications in
pharmaceutical & medical fields.
AB - Porous microspheres have interconnective external and internal pores leading to
very low mass density and enormous specific surface area, enabling them to have
excellent adsorption capabilities. Due to this uniqueness over traditional
microsphere, they find extensive pharmaceutical applications. Porous microspheres
are very promising for gastro retentive drug delivery, alveoli targeted drug
delivery, high-speed chromatography, development of tissue regeneration scaffolds
and as carrier of biopharmaceuticals. Pore structure and porosity are the main
factors that govern their applications. There are different well-established
methods for their synthesis, like seed swelling, solvent evaporation,
polymerization, spray drying and phase separation. But most of the methods are
time consuming and consists of numbers of complicated steps. The size, shape and
pore structure of the particles depend on many experimental variables like
temperature, pH, stirring speed, type and concentration of porogen, polymer and
its concentration. Thus, synthesis of porous microparticle with predefined
porosity is really challenging.
PMID- 29940298
TI - Intra-articular nonviral gene therapy in mucopolysaccharidosis I mice.
AB - Mucopolysaccharidosis type I (MPS I) is caused by the lysosomal accumulation of
glycosaminoglycans (GAGs) due to the deficiency of the enzyme alpha-L-iduronidase
(IDUA). Currently available treatments may improve several clinical
manifestations, but they have limited effects on joint disease, resulting in
persistent orthopedic complications and impaired mobility. Thus, this study aimed
to perform an intra-articular administration of cationic nanoemulsions complexed
with the plasmid encoding for the IDUA protein (pIDUA) targeting MPS I gene
therapy for the synovial joints. Formulations composed of DOPE, DOTAP, MCT (NE),
and DSPE-PEG (NE-PEG) were prepared by high-pressure homogenization, and the
pIDUA plasmid was associated by adsorption onto the surface of nanoemulsions
(pIDUA/NE or pIDUA/NE-PEG). The physicochemical characterization showed that the
presence of DSPE-PEG in pIDUA/NE-PEG formulations led to small and highly stable
droplets even when incubated with simulated synovial fluid (SSF), when compared
to the non-pegylated complexes (pIDUA/NE). Uptake by fibroblast-like synoviocytes
(FLS) was demonstrated, and high cell viability (70%) in addition with increased
IDUA activity (2.5% of normal) were observed after incubation with pIDUA/NE-PEG.
The intra-articular injection of pIDUA/NE-PEG complexes in MPS I mice showed that
the complexes were localized in the joints, were able to transfect synovial
cells, and thus promoted an increase in IDUA activity and expression in the
synovial fluid, with no significant activity in other tissues (kidney, liver,
lung, and spleen). The overall results demonstrated a contained, safe, tolerable,
and effective in situ approach of nonviral intra-articular gene therapy targeting
the reduction or prevention of the debilitating orthopedic complications of MPS I
disorder.
PMID- 29940299
TI - Optimizing feed frame design and tableting process parameters to increase die
filling uniformity on a high-speed rotary tablet press.
AB - Despite the high quantities of tablets produced daily, many tableting processes
are still operated at sub-optimal settings and hence lack the necessary
flexibility to mitigate for possible process deviations. However, to ensure this
flexibility on tableting throughput it is important to select the most robust
feed frame design and settings regarding die-filling. In this research study,
four paddle designs for a two-compartment forced feeder (equipped with a metering
and a feeding paddle wheel) were evaluated at a wide range of process-settings
(i.e. tableting speed, paddle speed, overfill level) and feed frame features
(i.e. deaeration) for their impact on the die-filling step of a poorly flowing
model formulation (i.e. MCC 101) using a quality-by-design approach. No benefit
on die-filling was observed when using higher speeds of the metering paddle wheel
compared to the feeding paddle wheel, and no convincing arguments were obtained
to use the feed frame deaeration opening. Some combinations of paddle design and
process-settings significantly increased the risk for inconsistent die-filling
(i.e. high tablet weight variability) which can therefore limit the efficiency of
the tableting process. The approach used in this study enabled to compare the
paddle designs for their die-filling performance in function of varying tableting
speeds, eventually resulting in the selection of a feed frame design that is most
robust and therefore will provide a uniform die-filling over a wide range of
throughputs. Selection of the most robust parameters is an important prerequisite
for the ability of using the rotary tablet press as an agile unit-operation.
PMID- 29940300
TI - DPI formulations for high dose applications - Challenges and opportunities.
AB - This opinion piece gives reasons for high dose DPI applications, points out
challenges and shows opportunities and possible solutions for high dose DPI. This
piece of work shall set the stage for more in-depth reviews of state of the art
and research papers addressing the challenges of high dose DPI which shall be
included in the special issue of IJP.
PMID- 29940301
TI - Low internal exposure and absence of adverse effects in workers exposed to high
air levels of inorganic selenium.
AB - Selenium is an essential trace element for humans, but adverse health effects may
occur after elevated intake. The margin between it is small. This study aimed to
assess external and internal exposure in workers of a selenium-processing plant,
in which elemental and inorganic selenium occurred. Selenium was analyzed in the
form of the selenium concentration in plasma (Se-P), in erythrocytes (Se-RBC) and
in personal air samples (Setotal-Air) of 17 exposed workers. Internal exposure
was compared to 20 controls without occupational selenium exposure. For potential
effects, glucose, HbA1c, proinsulin, prothrombin time and GPX were determined.
Setotal-Air had a maximum of 2394 MUg/m3 (median 319 MUg/m3), containing a small
water-soluble fraction (median 12.7 MUg/m3, range 0.07-975 MUg/m3). Se-P of the
exposed ranged from 62 to 123 MUg/L (median 105 MUg/L), whereas the median of Se
RBC was 63.4 MUg/L blood (range 51.9-92.7 MUg/L). Both were significantly higher
than the controls. No significant difference was found for the effect parameters.
Biological effect monitoring of employees occupationally exposed to very high
levels of selenium and inorganic selenium compounds did not show any indication
of adverse health effects. The moderate increase of the internal selenium
exposure compared to the high ambient exposure to selenium and its compounds
suggests an efficient air protection or an extremely low resorption of elemental
and inorganic species of selenium via inhalation.
PMID- 29940302
TI - Biomonitoring of styrene occupational exposures: Biomarkers and determinants.
AB - INTRODUCTION: High styrene exposures are still experienced in various
occupational settings, requesting regular exposure assessments. The aims of this
study were to study occupational exposures in various industrial sectors and to
determine factors influencing styrene urinary metabolites levels. METHODS:
Biomonitoring was conducted in 141 workers from fiberglass-reinforced plastic
(FRP) manufacture, thermoplastic polymers production, vehicle repair shops and
cured-in-place pipe lining (CIPP). Urinary styrene (StyU) as well as Mandelic
(MA) / Phenyglyoxylic Acids (PGA) were quantified at the beginning and at the end
of week, and multivariate linear regression models were used. RESULTS: StyU
levels revealed very low, rarely exceeding 3 MUg.L-1. Highest concentrations of
MA + PGA were observed in FRP sector, with levels reaching up to 1100 mg.g-1 of
creatinine. Factors influencing end-of-week MA + PGA concentrations were levels
at the beginning of week, open molding processes, proximity to the emission
source, respiratory protection, styrene content in raw materials. Elevated levels
were also observed during CIPP process, whereas thermoplastic injection and
vehicle repair shop workers exhibited much lower exposures. CONCLUSIONS:
Intervention on process (decreasing styrene proportion, using closed molding),
protective equipment (local exhaust ventilation, respiratory protection) and
individual practices (stringent safety rules) are expected to decrease
occupational exposures. Urinary MA + PGA remain the most appropriate biomarkers
for occupational biomonitoring.
PMID- 29940304
TI - Reply to the Editor- Fusion during entrainment at the cavotricuspid isthmus: When
entrainment does not match our expectation.
PMID- 29940303
TI - Current Treatment of Bilateral Retinoblastoma: The Impact of Intraarterial and
Intravitreous Chemotherapy.
AB - PURPOSE: To evaluate the management and outcomes of naive bilateral
retinoblastoma treated at a single-center over a 5-year period during the era of
ophthalmic artery chemosurgery (OAC) and intravitreous chemotherapy. METHODS:
Retrospective cohort study of 46 patients (92 eyes) with naive bilateral
retinoblastoma treated at Memorial Sloan Kettering Cancer Center between January
2012 and February 2017. Indirect ophthalmoscopy, fundus photography,
ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical
response. Patient, ocular, ocular progression-free, ocular recurrent event-free,
and second ocular survivals were assessed by Kaplan-Meier estimates. Retinal
toxicity was evaluated by electroretinography. Snellen visual acuity and complete
blood count metrics were recorded. RESULTS: Sixty-four eyes (70%) in 41 patients
(89%) received ophthalmic artery chemosurgery as part of their treatment. Twenty
six patients (56%) received tandem OAC (bilateral simultaneous infusions). Seven
eyes were primarily enucleated. No eye receiving initial OAC was enucleated.
There was a single secondary enucleation in an eye initially treated with focal
therapy with anterior chamber recurrence. The 3-year Kaplan-Meier estimates for
overall ocular, secondary ocular (survival after treatment for recurrence),
progression-free, and recurrent event-free survival were 91.3% [95% confidence
interval (CI) 83.4-95.5], 98.7% (95% CI 91.3-99.8), 91.5% (95% CI 83.0-95.8), and
78.9% (95% CI 68.2-86.3), respectively. Overall and secondary ocular survivals
were 100% for International Classification of Retinoblastoma (ICRB) groups A-C.
Overall ocular survival was 91.5% (95% CI 70-97.8) for ICRB group D and 71.4%
(95% CI 47.1-79.4) for group E. Secondary ocular survival was 95.4% (95% CI 71.8
99.3) for ICRB group D and 100% for group E. There were no treatment-related
deaths, three patients developed trilateral retinoblastoma (one died), and one
patient (who did not receive OAC) developed metastatic disease and is in
remission at 32-month follow-up. CONCLUSION: The majority (89%) of bilateral
retinoblastoma patients in the current era and at this center were treated with
OAC. This has resulted in saving a historic number of eyes. A quarter of eyes
developed recurrent disease (defined as recurrent disease requiring any treatment
including focal), the majority of which occurred in the first year after
treatment, and all but one was saved. There has been no compromise in patient
survival.
PMID- 29940305
TI - Long-term reverse remodeling by cardiac resynchronization therapy with MultiPoint
Pacing: A feasibility study of noninvasive hemodynamics-guided device
programming.
AB - BACKGROUND: Cardiac resynchronization therapy (CRT) with multipoint left
ventricular (LV) pacing (MultiPoint Pacing [MPP]) improves acute hemodynamics and
chronic outcomes in comparison to conventional biventricular pacing (BiV), though
MPP programming questions persist. OBJECTIVES: In this multicenter feasibility
study, we evaluated the feasibility of using noninvasive systolic blood pressure
(SBP) to guide MPP programming and assessed the chronic 6-month echocardiographic
CRT response. METHODS: Patients implanted with MPP-enabled CRT-defibrillator
devices underwent noninvasive hemodynamic assessment (finger arterial pressure)
during a pacing protocol that included atrial-only pacing and various BiV and MPP
configurations. Each configuration was repeated 4 times, alternating with a
reference pacing configuration, to calculate the SBP difference relative to
reference (DeltaSBP). CRT configurations with the greatest DeltaSBP were
programmed. An independent core laboratory analyzed baseline and 6-month
echocardiograms, with CRT response defined as a 6-month reduction in LV end
systolic volume >= 15%. RESULTS: Forty-two patients (71% male; LV ejection
fraction 30.3% +/- 7.5%; QRS duration 161 +/- 19 ms; 26% had ischemic
cardiomyopathy) were enrolled in 4 European centers. Relative to atrial-only
pacing, the best BiV and best MPP configurations produced significant SBP
elevations of 3.1 +/- 4.2 (P < .01) and 4.1 +/- 4.1 mm Hg (P < .01), respectively
(BiV vs MPP; P < .01). Greater SBP elevations were associated with the best MPP
compared with the best BiV configurations in 29 of 37 patients completing the
pacing protocol (78%). Of MPP-programmed patients completing the 6-month follow
up visit, 23 of 27 (85%) were classified as CRT responders (6-month reduction in
LV end-systolic volume 37.0% +/- 13.6%). CONCLUSION: Acute noninvasive
hemodynamics after CRT device implantation predominantly favored MPP over BiV
programming. MPP programming guided by noninvasive hemodynamics resulted in
positive LV structural remodeling.
PMID- 29940306
TI - To the Editor- Fusion during entrainment at the cavotricuspid isthmus: When
entrainment does not match our expectation.
PMID- 29940307
TI - Child abuse and neglect re-report rates for young children with developmental
delays.
AB - The study objective was to examine the likelihood and magnitude of child abuse
and neglect (CAN) re-reports for young children (0-71 months) with delays in
cognitive, language, and adaptive development, compared to typically developing
children. The National Survey of Child and Adolescent Well-Being (NSCAW II), a
nationally representative and longitudinal survey, was used to examine CAN re
reports at two follow-up waves, 18- and 36-months post baseline assessments.
Logistic regression models were employed to determine the correlation between
number of developmental delays and a CAN re-report at waves 2 and 3. Results
indicate that children with three or more domains of delays had odds 4.73 times
higher than children without developmental delays of re-report to CPS at wave 2
but not at wave 3. In this study, children with multiple developmental delays
have elevated rates of CAN re-reports when compared to typically developing
children. Allocation of child welfare resources should include strategies for
preventing maltreatment risk among children with developmental delays.
PMID- 29940308
TI - Eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis.
AB - OBJECTIVE: Eosinophilic gastrointestinal diseases (EGIDs) are a rare group of
disorders that can have varied clinical presentations dependent on the involved
segment within the gastrointestinal tract. Eosinophilic gastritis presents with
abdominal pain or vomiting, eosinophilic gastroenteritis presents with diarrhea
and anemia or hypoalbuminemia, and eosinophilic colitis can present with diarrhea
or bloody stools. These nonspecific symptoms remain poorly understood in their
relation to the underlying pathogenesis, but a significant percentage of patients
have atopy. In this review, we discuss the current literature on EGIDs to promote
a practical approach to diagnosis and care. DATA SOURCES: Review of published
literature. STUDY SELECTIONS: Clinically relevant literature from 1900 through
2018 was obtained from a PubMed search. Those that addressed prevalence,
diagnosis, clinical manifestations, natural history, and treatment of EGIDs were
reviewed and are summarized in this article. RESULTS: Of the 485 articles found
in the search, most of which were case reports, 71 were selected for review. The
natural history of EGIDs is based primarily on case series and small numbers of
patients, making therapeutic decisions difficult. Treatment remains limited to
dietary restriction that is not effective in many patients and topical or
systemic corticosteroids whose long-term use is to be avoided if possible.
CONCLUSION: With the seeming increase in all types of EGIDs, phenotypic
descriptions are emerging that will likely promote better understanding of the
pathogenesis and identification of novel therapeutic targets.
PMID- 29940309
TI - Risk factors for multiple epinephrine doses in food-triggered anaphylaxis in
children.
AB - BACKGROUND: Food-related anaphylactic reactions may require treatment with more
than 1 dose of epinephrine. Current guidelines advise patients at risk of
anaphylaxis to carry 2 epinephrine autoinjectors. OBJECTIVE: The objective of
this study was to determine risk factors of multiple-dose epinephrine treatment
in pediatric food-related anaphylaxis. METHODS: Parents of children with
physician-confirmed diagnosis of food allergy were administered a standardized
questionnaire at the time of their clinic visit. These patients were then
followed-up prospectively by phone. RESULTS: Six hundred forty-two subjects had
allergic reactions. Twenty-six percent of patients reported at least 1 reaction
treated with epinephrine, for a total of 221 reactions. Among reactions treated
with epinephrine, 24 reactions (11%) received 2 or more doses of epinephrine. The
most common triggers were milk (30%) and peanut (18%). Milk-triggered allergic
reactions (odds ratio [OR] 3.2; 95% confidence interval [CI] 1.2-8.4) and
treatment with oxygen (OR 5.0, 95% CI 2.0-12.4) were significant risk factors for
requiring multiple doses of epinephrine to treat an allergic reaction.
CONCLUSION: This study demonstrates that treatment of anaphylaxis may require
more than 1 epinephrine injection. Reactions triggered by milk or requiring
treatment with oxygen are at higher risk for needing more than 1 dose of
epinephrine. Families of food-allergic children should be counseled on the
importance of carrying 2 epinephrine auto-injectors.
PMID- 29940310
TI - Understanding caregiver goals, benefits, and acceptable risks of peanut allergy
therapies.
AB - BACKGROUND: Both oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT)
are emerging potential treatments for peanut allergy. Caregiver goals and
expectations of these therapies are poorly defined. OBJECTIVE: To determine
caregiver goals and expectations of food allergy therapy. METHODS: Twenty-two
detailed, semistructured interviews of OIT and EPIT caregivers were conducted,
allowing caregivers to describe their motivations for and experiences with food
allergy therapy and life with a peanut allergic child. RESULTS: In this sample,
caregivers of peanut allergic children enrolled in OIT or EPIT phase 3 trials
expressed a primary goal for their child to develop a buffer against an
unintentional peanut exposure. The perception of the buffer varied, representing
a decreased reaction severity on exposure, increased time to react to allow for
assessment, or increased threshold of peanut exposure tolerated. Although
caregivers expressed that a buffer may increase their confidence in travel and
dining outside the home, they do not anticipate this buffer would lessen their
overall level of pretherapy anxiety, allergen-associated vigilance, or avoidance
practices. Most of the caregivers hope the buffer will increase their and their
child's perceived sense of freedom for the child's actions and social
interactions, translating to quality of life improvement, while still respecting
the limitations of having a severe allergy that has been partially treated. No
caregiver viewed these therapies as a cure, and most viewed treatment as a
supplement to their current avoidance practices. CONCLUSION: Caregivers of peanut
allergic children strongly desire that OIT and EPIT result in a buffer against an
unintentional reaction, although most admitted that this would not significantly
change their anxiety and family's current lifestyle.
PMID- 29940312
TI - Essential Intracrine Androgenic Action in Lung Development for Both Sexes.
AB - Albeit their recognized negative effects on lung maturation, androgens have been
proposed to play an essential positive role in lung development. This work aimed
to evaluate the impact of blocking endogenous androgen and estrogen actions and
to study the effect of an excess of androgen and estrogen during the end of
saccular stage and the beginning of the alveolar stage on lung development. This
was performed with normal oxygen atmosphere and with hyperoxia, a model of
alveolar simplification, which is observed in new bronchopulmonary dysplasia.
Mouse lung samples were collected on postnatal day 9 after exposure to 21% or 80%
oxygen (postnatal days 1 to 4), and after administration (postnatal days 3 to 8)
of vehicle, pure antiandrogen (flutamide), dihydrotestosterone, pure antiestrogen
(fulvestrant), or 17beta-estradiol. With 21% oxygen, the major effects on
morphometric parameters were induced by flutamide. In contrast, with hyperoxia,
both flutamide and dihydrotestosterone had similar effects on several
morphometric parameters. For instance, a decrease in the relative frequency of
closed areas (mainly composed of saccules/alveoli) < 1000 MUm2 and an increase
for those > 2500 MUm2 were observed after flutamide administration. In
conclusion, during the junction between the saccular and the alveolar stages,
endogenous androgens play an essential intracrine role in lung development for
both sexes while an excess of androgens are deleterious when combined with a
hyperoxia treatment, but not with normal oxygen levels. Endogenous estrogens have
no effects on the lungs during the developmental window studied, while exogenous
estrogens had only isolated effects on some morphometric parameters.
PMID- 29940311
TI - NR3E receptors in cnidarians: A new family of steroid receptor relatives extends
the possible mechanisms for ligand binding.
AB - Steroid hormone receptors are important regulators of development and physiology
in bilaterian animals, but the role of steroid signaling in cnidarians has been
contentious. Cnidarians produce steroids, including A-ring aromatic steroids with
a side-chain, but these are probably made through pathways different than the one
used by vertebrates to make their A-ring aromatic steroids. Here we present
comparative genomic analyses indicating the presence of a previously undescribed
nuclear receptor family within medusozoan cnidarians, that we propose to call
NR3E. This family predates the diversification of ERR/ER/SR in bilaterians,
indicating that the first NR3 evolved in the common ancestor of the placozoan and
cnidarian-bilaterian with lineage-specific loss in the anthozoans, even though
multiple species in this lineage have been shown to produce aromatic steroids,
whose function remain unclear. We discovered serendipitously that a cytoplasmic
factor within epidermal cells of transgenic Hydra vulgaris can trigger the
nuclear translocation of heterologously expressed human ERalpha. This led us to
hypothesize that aromatic steroids may also be present in the medusozoan
cnidarian lineage, which includes Hydra, and may explain the translocation of
human ERalpha. Docking experiments with paraestrol A, a cnidarian A-ring aromatic
steroid, into the ligand-binding pocket of Hydra NR3E indicates that, if an
aromatic steroid is indeed the true ligand, which remains to be demonstrated, it
would bind to the pocket through a partially distinct mechanism from the manner
in which estradiol binds to vertebrate ER.
PMID- 29940313
TI - Hematologic Considerations and Management of Adolescent Girls with Heavy
Menstrual Bleeding and Anemia in US Children's Hospitals.
AB - STUDY OBJECTIVE: To assess the frequency, severity, and inpatient management of
girls admitted with heavy menstrual bleeding and iron deficiency anemia at US
children's hospitals, with a focus on hematologic considerations. DESIGN:
Retrospective multicenter cohort study from October 2012 through September 2015.
SETTING: Children's hospitals submitting data to the Pediatric Health Information
System. PARTICIPANTS: Female patients, age 8-18 years, admitted with heavy
menstrual bleeding and anemia as either a primary or secondary diagnosis.
Patients with cancer, immune thrombocytopenic purpura, aplastic anemia, and
pregnancy were excluded. INTERVENTIONS AND MAIN OUTCOME MEASURES: Hemostatic
evaluation; provision of iron therapy. RESULTS: We identified 1183 admissions
(1134 unique patients). Patients' median (interquartile range) age was 14 (11-17)
years. Forty-one percent were Caucasian (n = 480), 31% African American (n =
371), and 26% Hispanic ethnicity (n = 310). Intensive care use occurred in 5% of
admissions (n = 56). Hemostatic assessment was inconsistent; 15% (n = 182) had no
such evaluation. Two-thirds (n = 797; 67%) involved transfusions, 37% (n = 433)
received no inpatient iron therapy, and 17% (n = 197) received no hormonal or
antifibrinolytic therapy. Hemostatic evaluation was associated with intensive
care use: odds ratio (OR), 4.80 (95% confidence interval [CI], 1.16-19.86; P =
.03); emergency department visit: OR, 2.60 (95% CI, 1.86-3.65; P < .01); private
insurance: OR, 1.62 (95% CI, 1.12-2.35; P = .01); and younger age: OR, 0.84 (95%
CI, 0.77-0.92; P < .01). CONCLUSION: Hundreds of girls with heavy menstrual
bleeding and anemia are hospitalized at US children's hospitals each year with
variable inpatient hematologic evaluation and management. Future guidelines
should emphasize early identification of at-risk patients and promote effective
implementation strategies to reduce the burden of this preventable complication.
PMID- 29940314
TI - Noncytotoxic-Related Primary Ovarian Insufficiency in Adolescents: Multicenter
Case Series and Review.
AB - STUDY OBJECTIVE: Primary ovarian insufficiency (POI) in adolescents not due to
cytotoxic therapy has not been well studied. Causes of POI have been described in
adults, but adolescents might represent a unique subset necessitating a targeted
approach to diagnosis, workup, and treatment. We sought to better characterize
adolescent POI through a descriptive multicenter study. DESIGN: Case series of
patients with POI. SETTING: Six tertiary care institutions. PARTICIPANTS:
Patients presenting from 2007 to 2014 aged 13-21 years diagnosed with
noncytotoxic POI, with exclusions for those who received gonadotoxic therapy,
with 46XY gonadal dysgenesis, or lack of evidence of hypergonadotropic
hypogonadism on chart review. INTERVENTIONS: Review and data extraction of
records identified according to International Classification of Diseases Ninth or
Tenth Revision codes. MAIN OUTCOME MEASURES: Data were analyzed for signs and
symptoms, workup, and treatments. Complete workup was on the basis of American
College of Obstetricians and Gynecologists guidelines. Characteristics of
patients with POI who presented with delayed puberty/primary amenorrhea vs
secondary amenorrhea were compared. RESULTS: One hundred thirty-five records were
identified. Those who had received cytotoxic therapy (n = 52), 46XY gonadal
dysgenesis (n = 7), or on review did not have POI (n = 19) were excluded. Of 57
remaining cases, 16 were 45X, 2 had galactosemia, and 4 had X-chromosome
abnormalities. Most did not undergo full etiologic evaluation. Girls diagnosed
after primary amenorrhea/delayed puberty were less symptomatic and more likely to
receive an estrogen patch than those diagnosed after secondary amenorrhea.
CONCLUSION: Noncytotoxic POI in adolescents is an uncommon condition with, to our
knowledge, only 64 cases in 6 institutions over 7 years. These patients might not
undergo complete etiological workup. Aside from 45X, the most common etiologies
were X-chromosome abnormalities or galactosemia.
PMID- 29940315
TI - Clindamycin anaphylaxis confirmed by in vivo and in vitro testing.
PMID- 29940316
TI - Trimethoprim-sulfamethoxazole induces acute pancreatitis associated with drug
specific cytotoxic T lymphocytes.
PMID- 29940317
TI - Facile preparation of Ni nanowire embedded nitrogen and sulfur dual-doped carbon
nanofibers and its superior catalytic activity toward urea oxidation.
AB - A novel hairy-shaped Ni nanowire embedded nitrogen and sulfur dual-doped carbon
nanofibers (Ni/N,S-CNFs) with superior electrocatalytic properties for urea
oxidation reaction (UOR) was reported. The Ni/N,S-CNFs was prepared by
electrospinning and carbonization process, using melamine-trithiocyanuric acid
(MTCA) aggregates as both the N and S element sources. Noteworthy, MTCA also
favored the formation of Ni nanowire via vapor liquid-solid mechanism, while Ni
nanoparticles loaded CNFs (Ni/CNFs) was obtained without MTCA. For UOR tests, a
high peak current intensity of 37.0 mA mg-1 was obtained on Ni/N,S-CNFs at 0.42 V
(vs. SCE), 2-times higher of that on Ni/CNFs. Besides, the catalytic stability of
Ni/N,S-CNFs was also improved. The enhanced catalytic properties of Ni/N,S-CNFs
for UOR were ascribed to its unique Ni nanowires structure as well as the N, S
dual-doping. Our work reveals that the property improvement of metal-based
catalysts could be achieved by the heteroatom doping to fine the metal
nanostructure.
PMID- 29940318
TI - Preparation and electrochemical properties of mesoporous NiCo2O4 double
hemisphere used as anode for lithium-ion battery.
AB - NiCo2O4 is a potential anode material for lithium ion battery due to its many
advantages, such as high theoretical capacitance, low cost, and good
electrochemical activity. In this study, mesoporous NiCo2O4 double-hemisphere (3
5 MUm) with high surface area (270.68 m2.g-1) and excellent electrochemical
performances has been synthesized through a facile precipitation method followed
with thermal treatment process. The prepared NiCo2O4 is pure phase and can be
indexed as a face-centered-cubic with a typical spinel structure. Electrochemical
tests show the prepared material has high specific capacities (910 mAh.g-1 at 100
mA.g-1), excellent cyclicity (908 mAh.g-1 at 100 mA.g-1 after 60 cycles) and
remarkable high rate performance (after 100 cycles, 585 mAh.g-1 at 400 mAh.g-1,
415 mAh.g-1 at 800 mAh.g-1 and 320 mAh.g-1 at 1600 mAh.g-1 with coulombic
efficiencies of almost 100%). The excellent performances of prepared NiCo2O4 are
mainly caused by the unique double-hemisphere structure, which has large surface
area, gives material more opportunity to contact with electrolyte and facilitates
lithium ion spreading into the material along the radical direction, resulting in
a promising application for next-generation lithium-ion batteries.
PMID- 29940319
TI - Acoustic activation of water-in-oil microemulsions for controlled salt
dissolution.
AB - HYPOTHESIS: The dynamic nature of the oil-water interface allows for
sequestration of material within the dispersed domains of a microemulsion.
Microstructural changes should therefore change the dissolution rate of a solid
surface in a microemulsion. We hypothesize that microstructural changes due to
formulation and cavitation in an acoustic field will enable control over solid
dissolution rates. EXPERIMENTS: Water-in-oil microemulsions were formulated using
cyclohexane, water, Triton X-100, and hexanol. The microstructure and solvation
properties of Winsor Type IV formulations were characterized. Dissolution rates
of KH2PO4 (KDP), were measured. A kinetic analysis isolated the effect of the
microstructure, and rate enhancements due to cavitation effects on the
microstructure were characterized by measuring dissolution rates in an ultrasonic
field. FINDINGS: Dispersed aqueous domains of 2-6 nm radius dissolve a solid
block of KDP at 0-10 nm/min. Dissolution rate is governed not by the domain
surface collision frequency but rather by a dissolution probability per domain
surface encounter. Higher probabilities are correlated with larger domains. Rapid
and reversible dissolution rate increases of up to 270* were observed under
ultrasonic conditions, with <20% of the increase due to bulk heating effects. The
rest is attributed to cavitation-induced changes to the domain microstructure,
providing a simple method for remotely activating and de-activating dissolution.
PMID- 29940320
TI - Switching charge transfer process of carbon nitride and bismuth vanadate by
anchoring silver nanoparticle toward cocatalyst free water reduction.
AB - With the aim of exploring and modulating the interfacial charge kinetics, a
ternary g-C3N4/Ag/BiVO4 was constructed with excellent photocatalytic performance
and preferable stability toward H2 evolution in absence of cocatalyst. Both
density functional theory (DFT) and experimental results implied that the type II
g-C3N4/BiVO4 composite can be switched to Z-scheme via Ag nanoparticles as the
electron shuttle. The optimal photocatalytic H2 yield rate achieved for g
C3N4/Ag/BiVO4 was 57.4 umol.g-1.h-1, being far surpassed the H2 harvest rate of g
C3N4/BiVO4, Ag/g-C3N4 and g-C3N4, which is 2.9, 14.8 and 1.7 umol.g-1.h-1,
respectively. The apparent quantum efficiency of g-C3N4/Ag/BiVO4 photocatalyst
was also determined to be 1.23%. Besides, the photocatalytic performance of g
C3N4/Ag/BiVO4 well preserved over 5 runs in 50 h. The improved H2 production
performance is considered as the consequence of promoted segregation of
photoexcited charge carriers and SPR effects of Ag nanoparticles. In combination
with photocurrent measurement, examination of active species and DFT calculation,
it is found that Ag nanoparticles as an electron mediator can highly promote the
Z-scheme carrier migration that electrons come from conduction band of BiVO4 will
quickly assemble with the photo-induced holes from valence band of g-C3N4,
leaving electrons in the conduction band of g-C3N4 and holes in valence band of
BiVO4 that could greatly enhance the charge separation efficiency.
PMID- 29940321
TI - Easy-handling bamboo-like polypyrrole nanofibrous mats with high adsorption
capacity for hexavalent chromium removal.
AB - Development of highly efficient and easy-handling absorbents for heavy metals
removal is desirable for the remediation of our existing aquatic system. Herein,
we demonstrated the novel bamboo-like polypyrrole nanofibrous mats for the
removal of highly toxic hexavalent chromium (Cr(VI)) from aqueous solution. To
achieve this target, the V2O5 nanofibrous templates were prepared via non
emulsion electrospinning technique and calcination, followed by in-situ
polymerization of pyrrole. Benefiting from the special porous structure, high
surface area and abundant adsorption active sites, the resulting bamboo-like
polypyrrole nanofibrous mats exhibited a high Cr(VI) adsorption capacity up to
961.5 mg g-1 at room temperature, which can be well maintained for five
adsorption/desorption cycles. The adsorption capacity for Cr(VI) can be enhanced
with the decrease of pH and adsorption process belonged to the pseudo-second
order model. Furthermore, the adsorption isotherms of bamboo-like polypyrrole
nanofibrous mats fitted the Langmuir isotherm model, and the adsorption mechanism
of electrostatic attraction between bamboo-like polypyrrole nanofibers and Cr(VI)
was presented. More importantly, the flexible and integrated bamboo-like
polypyrrole nanofibrous membrane allowed easy handling during application, which
is potentially used for heavy metal removal from aqueous solution.
PMID- 29940322
TI - Role of carbon quantum dots in titania based photoelectrodes: Upconversion or
others?
AB - Carbon quantum dots (CQDs) were synthesized by a facile and green pyrolysis
method. The as-prepared CQDs show wide light absorption, tunable downconversion
photoluminescence (PL) properties and excellent "upconversion" luminescence
properties. CQDs were used to design the TiO2/CdS/C photoelectrodes for
photoelectrochemical hydrogen evolution. The role of the CQDs was investigated
based on the TiO2/CdS/C photoelectrodes. The results reveal that CQDs can enhance
light-harvesting efficiency and improve their charge separation and transfer
properties when coupled with conventional QD-sensitized photoelectrodes.
Nevertheless, the contribution of "upconversion" luminescence of CQDs to the
enhanced photoelectrochemical performance is negligible.
PMID- 29940323
TI - Bi2MoO6/BiFeO3 heterojunction nanofibers: Enhanced photocatalytic activity,
charge separation mechanism and magnetic separability.
AB - Uniform Bi2MoO6 nanosheets were grown in a high dispersed fashion on electrospun
BiFeO3 nanofibers via a solvothermal technique. The loading amount of Bi2MoO6 in
the Bi2MoO6/BiFeO3 heterojunction nanofibers could be controlled by adjusting the
precursor concentrations in the solvothermal process. The XPS analysis, energy
band position calculation and trapping experiments all proved that the
Bi2MoO6/BiFeO3 heterojunction is a Z-scheme heterojunction. The Z-scheme
Bi2MoO6/BiFeO3 heterojunction had a much higher photocatalytic activity in the
visible-light photodegradation of Rhodamine B (RhB) and tetracycline
hydrochloride (TC) than pure BiFeO3 nanofibers or pure Bi2MoO6 nanosheets. The
enhanced photocatalytic activity was attributed to the formation of Z-scheme
Bi2MoO6/BiFeO3 heterojunctions, which could be beneficial to the separation of
photogenerated electron-hole pairs. Moreover, the Bi2MoO6/BiFeO3 heterojunction
nanofibers could be easily separated under an external magnetic field via the
ferromagnetic BiFeO3. After several cycles, the photocatalytic activity of the
Bi2MoO6/BiFeO3 heterojunction no longer significantly decreased suggesting that
the Bi2MoO6/BiFeO3 heterojunction is stable. These Z-scheme Bi2MoO6/BiFeO3
heterojunction nanofibers with highly visible-light photocatalytic activity,
excellent chemical stability and magnetic separability could be useful in many
practical applications.
PMID- 29940325
TI - Design rules of heteroatom-doped graphene to achieve high performance lithium
sulfur batteries: Both strong anchoring and catalysing based on first principles
calculation.
AB - A number of observations have been reported on chemical capture and catalysis of
anchoring materials for lithium-sulfur batteries. Here, we propose the design
principles for the chemical functioned graphene as an anchor material to realize
both strong chemical trapping and catalysis. Through the first principle, the
periodic law is calculated from the theory. Seven different co-doping series were
investigated, e.g. MN4@graphene (M = V, Cr, Mn, Fe, Co, Ni, and Cu). From binding
energy, partial density of state, and charge density difference analysis, the
FeN4 and CrN4 co-doped graphene show good performance for the lithium-sulfur
battery from both strong anchoring and catalytic effects. For the most kinds of
Li2Sx (x = 1, 2, 4, 6, 8) absorption, two combinations can be achieved, including
S-bonding and Li-bonding. The competition between the MS and the NLi shows the
main difference of the co-doped configurations. Moreover, the S-bonding systems
have better performance for both moderate chemical trapping and strong catalysis.
The binding energies of Li2Sx and Li decomposed properties considered as the key
descriptors for the rational design of lithium-sulfur battery. Lastly, we offer
design rules for high performance lithium-sulfur batteries based on the chemical
functional graphene materials.
PMID- 29940324
TI - Monolayer grafting of aminosilane on magnetic nanoparticles: An efficient
approach for targeted drug delivery system.
AB - Magnetic nanoparticles (MNPs) with higher magnetization are highly desirable for
targeted drug delivery (TDD) systems, as it helps accumulation of drug at the
target site. However, functionalization of MNPs for drug binding reduces the
magnetization which affects the efficacy of TDD. Herein we report direct
functionalization of MNPs with (3-Aminopropyl)triethoxysilane (APTES) which
preserves the magnetization. Grafting density estimated by TGA and BET analysis
showed monolayer grafting of APTES on MNP surface. MNPs were comprehensively
characterized by XRD, HR-TEM, SQUID-VSM and FTIR. Anti-cancerous drug telmisartan
(TEL) was loaded on monolayer APTES grafted MNPs. In-vitro controlled drug
release and cytotoxicity study on PC-3 human prostate cancer cell line of TEL
conjugated MNPs are also discussed. This functionalization strategy can be
extended to other biomedical applications where higher magnetization is desired.
PMID- 29940326
TI - Spontaneous sensorimotor cortical activity is suppressed by deep brain
stimulation in patients with advanced Parkinson's disease.
AB - Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory
beta band activity in the subthalamic nucleus (STN). Deep brain stimulation (DBS)
of STN alleviates motor symptoms in PD and suppresses the STN beta band activity.
The effect of DBS on cortical sensorimotor activity is more ambiguous; both
increases and decreases of beta band activity have been reported. Non-invasive
studies with simultaneous DBS are problematic due to DBS-induced artifacts. We
recorded magnetoencephalography (MEG) from 16 advanced PD patients with and
without STN DBS during rest and wrist extension. The strong magnetic artifacts
related to stimulation were removed by temporal signal space separation. MEG
oscillatory activity at 5-25 Hz was suppressed during DBS in a widespread
frontoparietal region, including the sensorimotor cortex identified by the
cortico-muscular coherence. The strength of suppression did not correlate with
clinical improvement. Our results indicate that alpha and beta band oscillations
are suppressed at the frontoparietal cortex by STN DBS in PD.
PMID- 29940327
TI - Temperament traits and executive functions in Parkinson's disease.
AB - INTRODUCTION: Aim of the study was to evaluate the possible relationship between
Temperament traits and executive dysfunction in patients with Parkinson's disease
(PD). METHODS: Patients affected by PD diagnosed according to the UK Parkinson's
disease Society Brain Bank criteria were enrolled in the study. Patients with a
Mini Mental State Examination <24 were excluded from the study. The Temperament
and Character Inventory (TCI), a self-report questionnaire assessing the Harm
Avoidance (HA), Novelty Seeking (NS) and Reward Dependence (RD) temperamental
traits, has been performed. The executive functions were assessed with the
Frontal Assessment Battery (FAB). RESULTS: Fifty PD patients (28 men and 22
women; mean age 59.1 +/- 10.1 years) were enrolled. High HA (mean score 73.3 +/-
24.7) and a low NS score (24.2 +/- 18.7) were recorded. Fifteen (30%) patients
presented a pathological FAB score (<=13.5). Patients with a pathological FAB
score presented an HA score significantly higher than patients with normal FAB
score (respectively 84.9 +/- 13.7 versus 69.8 +/- 26.9; p = 0.045). At the
univariate analysis an association between high HA score and pathological FAB
score was found (OR 3.85, 95%CI 1.06-13.9; p-value 0.040). CONCLUSION: Our study
confirmed an association between executive disturbances and HA in PD patients,
possibly related to a common impairment of the frontostriatal circuits.
PMID- 29940328
TI - Overexpression of neuronal RNA-binding protein HuD increases reward induced
reinstatement of an instrumental response.
AB - The neuronal RNA-binding protein HuD is involved in synaptic plasticity and the
molecular mechanisms of learning and memory. Previously, we have shown that HuD
is upregulated after both spatial and addiction-associated forms of learning,
such as conditioned place preference. However, what role HuD plays in non-drug
dependent learning and memory is not fully understood. In order to elucidate the
role that HuD plays in non-drug appetitive behavior, we assessed mice over
expressing HuD (HuDOE) throughout the forebrain on the acquisition of an
instrumental response for a non-sucrose food reward utilizing a touch-screen
paradigm. Next, we examined whether HuD level would alter the extinction or
reward-induced reinstatement of responding. We found that HuDOE acquired and
extinguished the instrumental response at rates similar to control littermates
with no significant alterations in secondary measures of motor behavior or
motivation. However, HuDOE reinstated their responding for food reward at rates
significantly higher than control animals after a brief presentation of reward.
These results suggest that HuD positively regulates the reinstatement of natural
reward seeking and supports the role of HuD in forms of learning and memory
associated with seeking of appetitive rewards.
PMID- 29940329
TI - A shortened study design for embryo-fetal development studies in the minipig.
AB - The minipig is accepted from scientific and regulatory perspectives for the
safety evaluation of drug candidates on embryo-fetal development. The relative
size and the duration of gestation (112-115 days) in the minipig is, however,
considered a drawback compared with routine smaller species. We evaluated if
study duration and cost could be optimized without impacting scientific validity
by performing all terminal procedures around mid-gestation (60 days). At this
stage, minipig fetal size is not too dissimilar to full term rabbit and therefore
better suited to fetal processing/examination compared with at the end of
gestation. Despite encountering higher than anticipated embryo-fetal death,
morphological defects clearly associated with a known teratogen, pyrimethamine,
were detected. Although the gonads are poorly differentiated macroscopically at
mid-term, a histological examination confirmed that external sexing of the
fetuses was accurate. Double staining of the bone and cartilage of the mid-term
fetal skeleton allowed a more refined examination.
PMID- 29940330
TI - Vitamin E and vitamin C attenuate Di-(2-ethylhexyl) phthalate-induced blood
testis barrier disruption by p38 MAPK in immature SD rats.
AB - As an environmental endocrine disruptor, Di-(2-ethylhexyl) phthalate (DEHP)
affects blood-testis barrier (BTB)-associated proteins expression, which
compromises BTB integrity and causes infertility. Notably, DEHP-induced
testicular toxicity is related to oxidative stress, but the specific mechanism
remains unclear. Therefore, we sought to investigate this mechanism and determine
whether vitamin C and vitamin E administration would attenuate the BTB impairment
induced by DEHP in vivo and by Mono-(2-Ethylhexyl) Phthalate (MEHP) in vitro,
respectively. HE staining and EM found that DEHP exposure led to spermatogenesis
dysfunction and BTB disruption, respectively. The Western blot and
immunofluorescence results showed that DEHP exposure caused BTB impairment
through oxidative stress-mediated p38 mitogen-activated protein kinase (MAPK)
signaling pathway. Furthermore, Vitamin E and vitamin C could alleviate the
oxidative stress, block DEHP-induced spermatogenesis dysfunction and BTB
disruption by inhibiting p38 MAPK signaling pathway. In summary, vitamin E and
vitamin C are good candidates for the treatment of DEHP-induced male infertility.
PMID- 29940331
TI - Hydroxyurea embryotoxicity is enhanced in P53-deficient mice.
AB - Hydroxyurea, a ribonucleotide reductase inhibitor, is a potent teratogen in mice,
causing severe limb and skeletal defects. The exposure of gestation day nine
murine embryos to hydroxyurea elicits an early embryonic stress response that
involves activation of the P53 transcription factor. The impact of this P53
activation on the embryotoxicity of hydroxyurea- is not known. The goal of this
study was to test the hypothesis that P53 acts to suppress hydroxyurea
embryotoxicity. Trp53+/- timed pregnant mice were treated with saline or
hydroxyurea (200 or 400 mg/kg) on gestation day nine; fetuses were examined for
viability and external and skeletal malformations on gestation day eighteen.
Neither the deletion of Trp53 nor hydroxyurea treatment significantly affected
fetal growth although a trend towards a decrease in fetal weights was observed in
Trp53-/- fetuses. However, hydroxyurea induced a significantly higher incidence
of malformations and resorptions in Trp53-/- fetuses compared to their wildtype
littermates. Thus, fetal P53 genotype is an important determinant of the effects
of hydroxyurea on organogenesis-stage embryos.
PMID- 29940332
TI - Creating Individual Surgeon Performance Assessments in a Statewide Hospital
Surgical Quality Improvement Collaborative.
AB - BACKGROUND: Surgeon performance profiling is of great interest to surgeons,
hospitals, health plans, and the public, yet efforts to date have been contested,
with stakeholders at odds over the selection, reliability, and validity of
metrics used. We sought to create surgeon-level comparative assessments within
the Illinois Surgical Quality Improvement Collaborative. STUDY DESIGN: American
College of Surgeons NSQIP data were obtained for 51 Illinois hospitals covering a
30-month period from 2014 to 2016. Surgeon-level, risk-adjusted outcomes rates
were estimated from 3-level crossed random effects logistic regression models and
classified as low, as expected, or high for each of 7 postoperative outcomes.
Model intra-class correlations and provider-specific reliability statistics were
calculated. RESULTS: A total of 123,141 cases were analyzed for 2,724 surgeons.
Median provider case volume was 17 (interquartile range 4 to 54). Overall crude
complication rates ranged from 0.62% to 7.14% across the 7 outcomes investigated.
Surgeon-level variance estimates were low (intra-class correlation coefficients
between 0.007 and 0.074). No performance outliers were detected for 3 of the
outcomes measures, while a small number of outliers were identified for any
morbidity (11 surgeons), surgical site infection (10 surgeons), death or serious
morbidity (8 surgeons), and reoperation (1 surgeon). Among all physicians, median
reliability was below 0.1 for each outcome. CONCLUSIONS: Few individual surgeon
performance outliers could be detected in NSQIP clinical registry data for a
statewide hospital collaborative over a 30-month period using postoperative
patient outcomes. Low surgeon-specific case volumes and minimal variance between
surgeons may limit the utility of American College of Surgeons NSQIP outcomes
measures for individual profiling. Alternative metrics, such as process measures,
patient experience, composite measures, or technical skill assessments should be
explored for surgeon-level measurement.
PMID- 29940334
TI - Population structure of OXA-48-producing Klebsiella pneumoniae ST405 isolates
during a hospital outbreak characterised by genomic typing.
AB - OBJECTIVES: The aim of this study was to investigate the structure of a broad and
sustained hospital outbreak of OXA-48-producing Klebsiella pneumoniae (KpO48)
belonging to sequence type 405 (ST405). METHODS: Whole-genome sequencing and
comparison of ten ST405 KpO48 isolates obtained from clinical samples in our
hospital was performed. Using stringent criteria, 36 single nucleotide
polymorphisms (SNPs) were detected (range 0-21 in pairwise comparisons), and
allele-specific PCR was used to call the SNPs among a larger set of isolates.
RESULTS: Several haplotypes were identified within the population. The haplotypes
did not show a spatial structure, but a temporal evolution of sequential
haplotype replacements was observed. CONCLUSIONS: The dispersed spatial
distribution suggests a reservoir formed by a large pool of colonised patients,
and the temporal replacement pattern suggests that the sustained outbreak was
composed of several small outbreaks that appeared and rapidly dispersed to
several units.
PMID- 29940333
TI - Both perforin and FasL are required for optimal CD8 T cell control of
autoreactive B cells and autoantibody production in parent-into-F1 lupus mice.
AB - To test the relative roles of perforin (pfp) vs. FasL in CTL control of
autoreactive B cell expansion, we used the parent-into-F1 model of murine graft
vs.-host disease in which donor CD8 CTL prevent lupus like disease by eliminating
activated autoreactive B cells. F1 mice receiving either pfp or FasL defective
donor T cells exhibited an intermediate short-term phenotype. Pairing of purified
normal CD4 T cells with either pfp or FasL defective CD8 T cell subsets resulted
in impaired host B cell elimination and mild lupus like disease that was roughly
equivalent in the two experimental groups. Thus, in addition to major roles in
tumor and intracellular pathogen control, pfp mediated CD8 CTL killing plays a
significant role in controlling autoreactive B cell expansion and lupus
downregulation that is comparable to that mediated by FasL killing. Importantly,
both pathways are required for optimal elimination of activated autoreactive B
cells.
PMID- 29940335
TI - Group medical visits after heart failure hospitalization: Study protocol for a
randomized-controlled trial.
AB - A primary goal of this research project is to better understand how shared
medical appointments (SMAs) can improve the health status and decrease
hospitalization and death for patients recently discharged with heart failure
(HF) by providing education, disease state monitoring, medication titration, and
social support to patients and their caregivers. We propose a 3-site randomized
controlled efficacy trial with mixed methods to test a SMA intervention, versus
usual care. Patients within 12 weeks of a HF hospitalization will be randomized
to receive either HF-SMA (intervention arm) with optional co-participation with
their caregivers, versus usual care (control arm). The HF-SMA will be provided by
a non-physician team composed of a nurse, a nutritionist, a health psychologist,
a nurse practitioner and/or a clinical pharmacist and will consist of four
sessions of 2-h duration that occur every other week for 8 weeks. Each session
will start with an assessment of patient needs followed by theme-based disease
self-management education, followed by patient-initiated disease management
discussion, and conclude with break-out sessions of individualized disease
monitoring and medication case management. The study duration will be 180 days
for all patients from the day of randomization. The primary study hypothesis is
that, compared with usual care, patients randomized to HF-SMA will experience
better cardiac health status at 90 and 180 days follow-up. The secondary
hypotheses are that, compared to usual care, patients randomized to HF-SMA will
experience better overall health status, a combined endpoint of hospitalization
and death, better HF self-care behavior, and lower B-type natriuretic peptide
levels.
PMID- 29940337
TI - Glycogen synthase kinase-3beta inhibition enhances myelination in preterm
newborns with intraventricular hemorrhage, but not recombinant Wnt3A.
AB - Intraventricular hemorrhage (IVH) in preterm infants results in reduced
proliferation and maturation of oligodendrocyte progenitor cells (OPCs), and
survivors exhibit reduced myelination and neurological deficits. Wnt signaling
regulates OPC maturation and myelination in a context dependent manner. Herein,
we hypothesized that the occurrence of IVH would downregulate Wnt signaling, and
that activating Wnt signaling by GSK-3beta inhibition or Wnt3A recombinant human
protein (rh-Wnt3A) treatment might promote maturation of OPCs, myelination of the
white matter, and neurological recovery in premature rabbits with IVH. These
hypotheses were tested in autopsy samples from preterm infants and in a rabbit
model of IVH. Induction of IVH reduced expressions of activated beta-catenin, TCF
4, and Axin2 transcription factors in preterm newborns. Both AR-A014418 (ARA) and
Wnt-3A treatment activated Wnt signaling. GSK-3beta inhibition by intramuscular
ARA treatment accelerated maturation of OPCs, myelination, and neurological
recovery in preterm rabbits with IVH compared to vehicle controls. In contrast,
intracerebroventricular rh-Wnt3A treatment failed to enhance myelination and
neurological function in rabbits with IVH. ARA treatment reduced microglia
infiltration and IL1beta expression in rabbits with IVH relative to controls,
whereas Wnt3A treatment elevated TNFalpha, IL1beta, and IL6 expression without
affecting microglia density. GSK-3beta inhibition downregulated, while rh-Wnt3A
treatment upregulated Notch signaling; and none of the two treatments affected
the Sonic-Hedgehog pathway. The administration of ARA or rh-Wnt3A did not affect
gliosis. The data suggest that GSK-3beta inhibition promoted myelination by
suppressing inflammation and Notch signaling; and Wnt3A treatment failed to
enhance myelination because of its pro-inflammatory activity and synergy with
Notch signaling. GSK-3beta inhibitors might improve the neurological outcome of
preterm infants with IVH.
PMID- 29940338
TI - The devil is in the mesoscale: Mechanical and behavioural heterogeneity in
collective cell movement.
AB - Heterogeneity within cell populations can be an important aspect affecting their
collective movement and tissue-mechanical properties, determining for example
their effective viscoelasticity. Differences in cell-level properties and
behaviour within a group of moving cells can give rise to unexpected and non
intuitive behaviours at the tissue level. Such emergent phenomena often manifest
themselves through spatiotemporal patterns at an intermediate 'mesoscale' between
cell and tissue scales, typically involving tens of cells. Focussing on the
development of embryonic animal tissues, we review recent evidence for the
importance of heterogeneity at the mesoscale for collective cell migration and
convergence and extension movements. We further discuss approaches to incorporate
heterogeneity into computational models to complement experimental
investigations.
PMID- 29940336
TI - alpha-Methyl-alpha-phenylsuccinimide ameliorates neurodegeneration in a C.
elegans model of TDP-43 proteinopathy.
AB - The antiepileptic drug ethosuximide has recently been shown to be neuroprotective
in various Caenorhabditis elegans and rodent neurodegeneration models. It is
therefore a promising repurposing candidate for the treatment of multiple
neurodegenerative diseases. However, high concentrations of the drug are required
for its protective effects in animal models, which may impact on its
translational potential and impede the identification of its molecular mechanism
of action. Therefore, we set out to develop more potent neuroprotective lead
compounds based on ethosuximide as a starting scaffold. Chemoinformatic
approaches were used to identify compounds with structural similarity to
ethosuximide and to prioritise these based on good predicated blood-brain barrier
permeability and C. elegans bioaccumulation properties. Selected compounds were
initially screened for anti-convulsant activity in a C. elegans pentylenetetrazol
induced seizure assay, as a rapid primary readout of bioactivity; and then
assessed for neuroprotective properties in a C. elegans TDP-43 proteinopathy
model based on pan-neuronal expression of human A315T mutant TDP-43. The most
potent compound screened, alpha-methyl-alpha-phenylsuccinimide (MPS), ameliorated
the locomotion defects and extended the shortened lifespan of TDP-43 mutant
worms. MPS also directly protected against neurodegeneration by reducing the
number of neuronal breaks and cell body losses in GFP-labelled GABAergic motor
neurons. Importantly, optimal neuroprotection was exhibited by external
application of 50 MUM MPS, compared to 8 mM for ethosuximide. This greater
potency of MPS was not due to bioaccumulation to higher internal levels within
the worm, based on 1H-nuclear magnetic resonance analysis. Like ethosuximide, the
activity of MPS was abolished by mutation of the evolutionarily conserved FOXO
transcription factor, daf-16, suggesting that both compounds act via the same
neuroprotective pathway(s). In conclusion, we have revealed a novel
neuroprotective activity of MPS that is >100-fold more potent than ethosuximide.
This increased potency will facilitate future biochemical studies to identify the
direct molecular target(s) of both compounds, as we have shown here that they
share a common downstream DAF-16-dependent mechanism of action. Furthermore, MPS
is the active metabolite of another approved antiepileptic drug, methsuximide.
Therefore, methsuximide may have repurposing potential for treatment of TDP-43
proteinopathies and possibly other human neurodegenerative diseases.
PMID- 29940339
TI - Dissociating frequency and animacy effects in visual word processing: An fMRI
study.
AB - In an fMRI investigation of the neural representation of word frequency and
animacy, participants read high- and low-frequency words within living and
nonliving semantic categories. Both temporal (left fusiform gyrus) and parietal
(left supramarginal gyrus) activation patterns differentiated between animal and
tool words after controlling for frequency. Activation patterns in a smaller
ventral temporal region, a subset of the voxels identified in the animacy
contrast, differentiated between high- and low-frequency words after controlling
for animacy. Activation patterns in the larger temporal region distinguished
between high- and low-frequency words just as well as patterns within the smaller
region. However, in analyses by animacy category, frequency effects in these
temporal regions were significant only for tool, not for animal, words. Thus,
lexical word frequency information and semantic animacy category information are
conjointly represented in left fusiform gyrus activation patterns for some, but
not all, concrete nouns.
PMID- 29940340
TI - Design, synthesis and biological evaluation of novel 1,2,3-triazole linked
coumarinopyrazole conjugates as potent anticholinesterase, anti-5-lipoxygenase,
anti-tyrosinase and anti-cancer agents.
AB - A series of new 1,2,3-triazole linked coumarinopyrazole conjugates 4a-e and 5a-e
have been synthesized via the Copper(I)-catalysed Alkyne-Azide Cycloaddition
(CuAAC). Going through the reaction of compound 2 with the 3-propargyl bromide
gave a mixture of propargylated regioisomers 3 + 3' used as a dipolarophile to
access to triazoles 4a-e and 5a-e. The structures of the prepared cycloadducts
were determined by 1H, 13C and 2D-NMR techniques and by HRMS analysis. All the
synthesized derivatives have been evaluated for their anticholinesterase, anti-5
lipoxygenase, anti-tyrosinase, and cytotoxic activities.
PMID- 29940341
TI - Design, synthesis of novel azolyl flavonoids and their protein tyrosine
Phosphatase-1B inhibitory activities.
AB - A series of azolyl flavonoids were synthesized and characterized by NMR, IR, MS
and HRMS spectra. All the newly prepared compounds were screened for their
potential protein tyrosine phosphatase inhibitory activities. Bioactive assay
manifested that most of the azolyl flavonoids exhibited good protein phosphatase
1B (PTP1B) inhibitory activities. Especially, triazolyl flavonoid 6a displayed
the best inhibitory activity (IC50 = 1.6 MUM) with 9.9-fold selectivity for PTP1B
over the closely related T-cell protein tyrosine phosphatase (TCPTP). Cell
viability assays indicated 6a has lower cytotoxicity. Molecular modeling and
dynamics studies revealed the reason of selectivity for PTP1B over TCPTP. Quantum
chemical studies were carried out on these compounds to understand the structural
features essential for activity.
PMID- 29940342
TI - Design, synthesis and antiplasmodial activity of novel imidazole derivatives
based on 7-chloro-4-aminoquinoline.
AB - A series of short chain 4-aminoquinoline-imidazole derivatives have been
synthesized in one pot two step multicomponent reaction using van leusen standard
protocol. The diethylamine function of chloroquine is replaced by substituted
imidazole derivatives containing tertiary terminal nitrogen. All the synthesized
compounds were screened against the chloroquine sensitive (3D7) and chloroquine
resistant (K1) strains of Plasmodium falciparum. Some of the compounds (6, 8, 9
and 17) in the series exhibited comparable activity to CQ against K1 strain of P.
falciparum. All the compounds displayed resistance factor between 0.09 and 4.57
as against 51 for CQ. Further, these analogues were found to form a strong
complex with hematin and inhibit the beta-hematin formation, therefore these
compounds act via heme polymerization target.
PMID- 29940343
TI - Comparison of different cytotoxicity assays for in vitro evaluation of mesoporous
silica nanoparticles.
AB - Colorimetric or luminogenic cytotoxicity assays are typically applied for in
vitro cytotoxicity evaluations due to their easy handling and low cost. However,
the results may be strongly assay-dependent. Furthermore, when applied to
nanoparticle toxicity screening, nanoparticle-specific interferences can occur.
Therefore, it is important to evaluate the assays for different classes of
nanoparticles. Mesoporous silica nanoparticles (MSNs) have emerged as a promising
platform for both diagnostic and therapeutic applications but a comparison
between the commonly employed colorimetric formazan-dependent MTT and WST-1 and
luminescent ATP-dependent cytotoxicity assays is still missing. In this work, we
evaluated the applicability of four different in vitro cell viability assays for
the cytotoxicity analysis of three differently functionalized mesoporous silica
nanoparticles towards TZM-bl indicator cells. The results derived from the
colorimetric measurements of cell-viability were compared with results obtained
by cell count experiments, flow cytometry, and optical microscopy. The
correlation between the viability assay results and the viable cell count was
observed to be both assay and particle dependent. The MTT assay generally
overestimated the cytotoxicity of the mesoporous silica particles, while the WST
1 assay sometimes clearly underestimated their cytotoxicity and even suggested a
viability exceeding 100%. Of the two ATP-based assays, the CellTiterGlo assay
gave the best correlation with cell count data, although some particle-dependent
effects were observed. In conclusion, ATP-based assays seem most suitable for in
vitro cytotoxicity evaluation of MSNs.
PMID- 29940344
TI - An investigation into E-cigarette cytotoxicity in-vitro using a novel 3D
differentiated co-culture model of human airways.
AB - Currently there is a lack of consensus on the possible adverse health effects of
E-cigarettes (ECs). Important factors including cell model employed and exposure
method determine the physiological relevance of EC studies. The present study
aimed to evaluate EC cytotoxicity using a physiologically relevant in-vitro
multicellular model of human airways. Human bronchial epithelial cells (CALU-3)
and pulmonary fibroblasts (MRC-5) were co-cultured at air-liquid-interface for 11
14 days post which they were exposed to whole cigarette smoke (WCS) or EC vapour
(ECV) at standard ISO-3308 regime for 7 m using a bespoke aerosol delivery
system. ECV effects were further investigated at higher exposure times (1 h-6 h).
Results showed that while WCS significantly reduced cell viability after 7 m, ECV
decreased cell viability only at exposure times higher than 3 h. Furthermore, ECV
caused elevated IL-6 and IL-8 production despite reduced cell viability. ECV
exposure also produced a marked increase in oxidative stress. Finally, WCS but
not ECV exposure induced caspase 3/7 activation, suggesting a caspase independent
death of ECV exposed cells. Overall, our results indicate that prolonged ECV
exposure (>=3 h) has a significant impact on pro-inflammatory mediators'
production, oxidative stress and cell viability but not caspase 3/7 activity.
PMID- 29940345
TI - Puzzling mosaics in cerebrospinal fluid.
PMID- 29940346
TI - Fever in the tropics: the ultimate clinical challenge?
PMID- 29940347
TI - 18th International Congress on Infectious Diseases/XVIII Congreso SADI 2018-It
takes two to Tango.
PMID- 29940348
TI - First detection and molecular identification of Borrelia species in Bactrian
camel (Camelus bactrianus) from Northwest China.
AB - Comprehensive epidemiological surveys for Lyme disease have not been conducted
for the Bactrian camel in China. In this study, a total of 138 blood specimens
collected from Bactrian camels from Zhangye City in Gansu Province and Yili and
Aksu in Xinjiang Province, China, were examined for the presence of Borrelia spp.
Species-specificity nested PCR based on the 5S-23S rRNA, OspA, flaB and 16S rRNA
genes revealed that the total positive rate of Borrelia spp. was 3.6% (5/138, 95%
CI = 0.2-17.9). These results were confirmed by sequence analysis of the positive
PCR products or positive colonies. This is the first report of Borrelia pathogens
in camels in China. Two Borrelia species that cause Lyme disease and one that
causes relapsing fever were identified in the camel blood samples by sequencing.
The findings of this study indicate that the Bactrian camel may serve as a
potential natural host of Lyme disease and/or relapsing fever in China.
PMID- 29940349
TI - Transcutaneous vagal nerve stimulatio (t-VNS): An adjunctive treatment option for
refractory epilepsy.
AB - PURPOSE: The aim of this trial was to investigate the efficacy and safety of
transcutaneous vagal nerve stimulation (t-VNS) in the palliative treatment of
drug resistant epileptic patients ineligible for surgery. METHODS: Twenty adult
patients received four hours of t-VNS per day for six months (T1), followed by a
two-month washout period (T2). The frequency and type of seizures recorded at T1
and T2 were compared with those occurring in the three months preceding study
entry (T0). Responders (>30% reduction in the total number of seizures)
subsequently received two hours of t-VNS per day for further six months (T3). All
patients underwent electroencephalography (EEG) and completed the Quality of Life
in Epilepsy questionnaire at baseline and T1. RESULTS: At T1 six patients were
considered responders. In these patients, at T3 the average reduction in seizure
frequency was 60% compared to T0 (p = 0.043), and 51% compared to T2 (p = 0.043).
Responders had more often seizures with falls (5 of 6; 83.3%) compared with non
responders (3 of 14; 21.4%) (p = 0,010) and t-VNS reduced their frequency by a
percentage ranging from 47.5 to 100%. There was no change in responders' EEG
findings after stimulation. At the end of the trial, three responders continued t
VNS, one implanted VNS. CONCLUSIONS: t-VNS had no or minimal side effects and
significantly reduced seizures in about one third of the enrolled patients.
Further studies should be planned to assess whether t-VNS is a suitable tool to
predict the efficacy of implanted VNS.
PMID- 29940350
TI - Gyrodactylus medaka n. sp. (Monogenea: Gyrodactylidae) parasitic on wild and
laboratory-reared medaka Oryzias latipes (Beloniformes: Adrianichthyidae) in
Japan.
AB - Gyrodactylus medaka n. sp. (Monogenea: Gyrodactylidae) is described from the
skin, fins, and gills of medaka Oryzias latipes (Beloniformes: Adrianichthyidae)
from Japan. This new species was collected from wild medaka in Hiroshima, Aichi,
Saga, and Kumamoto prefectures, and laboratory-reared medaka in Chiba and Aichi
prefectures. The small marginal hook sickle (<=4 MUm) and the length of the
marginal hook of the new species are the diagnostic morphological characters
differentiated from other gyrodactylids reported from Asia. The pairwise sequence
divergences for the interspecific variation in ITS regions and the phylogenetic
analysis suggest that the populations of G. medaka n. sp. may have a similar
genetic variation as the medaka populations in Japan. Gyrodactylus medaka n. sp.
and Dactylogyrus oryziasi (Monogenea: Dactylogyridae) can maintain their
populations in laboratory aquaria using medaka as their hosts, and these
monogeneans and medaka have the potential as experimental model animals for
clarifying various aspects of their host-parasite relationships. In addition, we
report the composition of modified ammonium picrate-glycerin (APG) and show it is
advantageous for monogenean taxonomy.
PMID- 29940351
TI - Extracellular superoxide dismutase (SOD3) regulates oxidative stress at the
vitreoretinal interface.
AB - Oxidative stress is a pathogenic feature in vitreoretinal disease. However, the
ability of the inner retina to manage metabolic waste and oxidative stress is
unknown. Proteomic analysis of antioxidants in the human vitreous, the
extracellular matrix opposing the inner retina, identified superoxide dismutase-3
(SOD3) that localized to a unique matrix structure in the vitreous base and
cortex. To determine the role of SOD3, Sod3-/- mice underwent histological and
clinical phenotyping. Although the eyes were structurally normal, at the
vitreoretinal interface Sod3-/- mice demonstrated higher levels of 3
nitrotyrosine, a key marker of oxidative stress. Pattern electroretinography also
showed physiological signaling abnormalities within the inner retina. Vitreous
biopsies and epiretinal membranes collected from patients with diabetic
vitreoretinopathy (DVR) and a mouse model of DVR showed significantly higher
levels of nitrates and/or 3-nitrotyrosine oxidative stress biomarkers suggestive
of SOD3 dysfunction. This study analyzes the molecular pathways that regulate
oxidative stress in human vitreous substructures. The absence or dysregulation of
the SOD3 antioxidant at the vitreous base and cortex results in increased
oxidative stress and tissue damage to the inner retina, which may underlie DVR
pathogenesis and other vitreoretinal diseases.
PMID- 29940353
TI - Cannabidiol induced apoptosis in human monocytes through mitochondrial
permeability transition pore-mediated ROS production.
AB - Cannabidiol (CBD) has been reported to induce apoptosis in immune cells through
oxidative stress-related mechanisms. The objective of the present study was to
investigate the cellular mechanisms for CBD-induced apoptosis and oxidative
stress in human monocytes. Exposure of freshly isolated human monocytes to CBD
induced apoptosis in a time- and concentration-dependent manner. Time-course
analyses revealed the induction of intracellular reactive oxygen species (ROS) at
1-2 h post CBD (16 MUM) exposure. By comparison, the CBD treatment rapidly
elicited the depolarization of mitochondrial membrane potential (MMP) within 5
min, and the oxidation of cardiolipin, a major lipid component of the
mitochondrial inner membrane, within 15 min. Moreover, CBD induced the release of
cytochrome c (Cyt c) from mitochondria. Mechanistic studies revealed that CBD
induced ROS production and apoptosis were not associated with the alteration of
mitochondrial superoxide dismutase activity, the electron leakage through
mitochondrial respiratory chain, and Fe2+- and Ca2+-mediated mechanisms. In
contrast, CBD-induced apoptosis and MMP depolarization were markedly attenuated
by the mitochondrial permeability transition pore (MPTP) inhibitor cyclosporin A
(CsA), but not the calcineurin inhibitor FK506. Furthermore, CsA prevented
cardiolipin oxidation and the MPTP opening induced by CBD. The present study
suggests that CBD acts on the mitochondria to elicit ROS generation and apoptosis
through MPTP opening and provides critical insights into the cellular mechanisms
for CBD-induced oxidative stress in apoptotic monocytes.
PMID- 29940352
TI - The cysteine-rich whey protein supplement, Immunocal(r), preserves brain
glutathione and improves cognitive, motor, and histopathological indices of
traumatic brain injury in a mouse model of controlled cortical impact.
AB - Traumatic brain injury (TBI) is a major public health problem estimated to affect
nearly 1.7 million people in the United States annually. Due to the often
debilitating effects of TBI, novel preventative agents are highly desirable for
at risk populations. Here, we tested a whey protein supplement, Immunocal(r), for
its potential to enhance resilience to TBI. Immunocal(r) is a non-denatured whey
protein preparation which has been shown to act as a cysteine delivery system to
increase levels of the essential antioxidant glutathione (GSH). Twice daily oral
supplementation of CD1 mice with Immunocal(r) for 28 days prior to receiving a
moderate TBI prevented an ~ 25% reduction in brain GSH/GSSG observed in untreated
TBI mice. Immunocal(r) had no significant effect on the primary mechanical injury
induced by TBI, as assessed by MRI, changes in Tau phosphorylation, and righting
reflex time or apnea. However, pre-injury supplementation with Immunocal(r)
resulted in statistically significant improvements in motor function (beam walk
and rotarod) and cognitive function (Barnes maze). We also observed a significant
preservation of corpus callosum width (axonal myelination), a significant
decrease in degenerating neurons, a reduction in Iba1 (microglial marker),
decreased lipid peroxidation, and preservation of brain-derived neurotrophic
factor (BDNF) in the brains of Immunocal(r)-pretreated mice compared to untreated
TBI mice. Taken together, these data indicate that pre-injury supplementation
with Immunocal(r) significantly enhances the resilience to TBI induced by a
moderate closed head injury in mice. We conclude that Immunocal(r) may hold
significant promise as a preventative agent for TBI, particularly in certain high
risk populations such as athletes and military personnel.
PMID- 29940354
TI - C60 fullerene accumulation in human leukemic cells and perspectives of LED
mediated photodynamic therapy.
AB - Recent progress in nanobiotechnology has attracted interest to a biomedical
application of the carbon nanostructure C60 fullerene since it possesses a unique
structure and versatile biological activity. C60 fullerene potential application
in the frame of cancer photodynamic therapy (PDT) relies on rapid development of
new light sources as well as on better understanding of the fullerene interaction
with cells. The aim of this study was to analyze C60 fullerene effects on human
leukemic cells (CCRF-CEM) in combination with high power single chip light
emitting diodes (LEDs) light irradiation of different wavelengths: ultraviolet
(UV, 365 nm), violet (405 nm), green (515 nm) and red (632 nm). The time
dependent accumulation of fullerene C60 in CCRF-CEM cells up to 250 ng/106 cells
at 24 h with predominant localization within mitochondria was demonstrated with
immunocytochemical staining and liquid chromatography mass spectrometry. In a
cell viability assay we studied photoexcitation of the accumulated C60
nanostructures with ultraviolet or violet LEDs and could prove that significant
phototoxic effects did arise. A less pronounced C60 fullerene phototoxic effect
was observed after irradiation with green, and no effect was detected with red
light. A C60 fullerene photoactivation with violet light induced substantial ROS
generation and apoptotic cell death, confirmed by caspase3/7 activation and
plasma membrane phosphatidylserine externalization. Our work proved C60 fullerene
ability to induce apoptosis of leukemic cells after photoexcitation with high
power single chip 405 nm LED as a light source. This underlined the potential for
application of C60 nanostructure as a photosensitizer for anticancer therapy.
PMID- 29940355
TI - The histone methyltransferase SETD1A regulates thrombomodulin transcription in
vascular endothelial cells.
AB - Thrombomodulin (TM, encoded by the THBD gene) expressed in vascular endothelial
cells plays pivotal roles maintaining the equilibrium of coagulation and anti
coagulation. TM levels can be regulated at the transcriptional level although the
epigenetic mechanism is underexplored. Here we report that transcriptional
activation of TM in both immortalized vascular endothelial cells (EAhy926) and
primary human aortic endothelial cells (HAEC) by all-trans retinoic acid (RA)
paralleled accumulation of trimethylated histone H3K4, a prominent marker for
active chromatin, surrounding the THBD promoter. RA treatment up-regulated the
expression of SETD1A (SET1), a dedicated H3K4 methyltransferase, and augmented
SETD1A occupancies on the THBD promoter. Further analysis revealed that the
sequence-specific transcription factor Kruppel-like factor 4 (KLF4) interacted
with and recruited SETD1A to the THBD promoter. Interestingly, SETD1A was
recruited to the KLF4 promoter by retinoic acid receptor (RAR) and mediated the
up-regulation of KLF4 expression by RA stimulation. In summary, our data
illustrate a previously unrecognized pathway in which SETD1A contributes to RA
induced TM expression in vascular endothelial cells by modulating the activity
and expression of KLF4.
PMID- 29940356
TI - Quinone group enhances the degradation of levofloxacin by aqueous permanganate:
Kinetics and mechanism.
AB - Quinone group is an important fraction of humic acid. The pseudo-first-order rate
constant (kobs) of levofloxacin (LF) degradation by permanganate (MnO4-)
significantly increased from 0.010 (without benzoquinone, BQ) to 0.042-0.443 min
1 at [BQ]o:[MnO4-]o (molar ratio) = 0.03-0.25 at pH 7.5, and an acidic pH
facilitated LF degradation. In the presence of BQ, MnO4- was first reduced to
Mn(II). Then, Mn(II) reacted with BQ to produce Mn(III) and semiquinone radical,
which was promoted under acidic conditions. With dissolved oxygen available,
Mn(III) further oxidized semiquinone radical to produce singlet oxygen (1O2) and
superoxide radical (O2-) as well as regenerate BQ. In addition, MnO4- could also
react with Mn(II) to produce Mn(III), whose complexation with semiquinone radical
in turn promoted this reaction. Due to the predominant scavenging of O2- by BQ,
1O2 and Mn(III) mainly contributed to the accelerated LF degradation, with a
notable formation of hydroxyl, ketone and endoperoxide groups in the degradation
byproducts. This study helps better understand the role of natural organic matter
in the degradation of organic micropollutants by MnO4- in water treatment.
PMID- 29940357
TI - Verifying community-wide exposure to endocrine disruptors in personal care
products - In quest for metabolic biomarkers of exposure via in vitro studies and
wastewater-based epidemiology.
AB - This study aimed to identify human specific metabolites of selected known or
suspected endocrine disruptors (EDCs), mainly UV filters, used in personal care
and consumer products whose metabolism has hardly been explored and to select
suitable candidate biomarkers for human exposure studies using wastewater based
epidemiology (WBE). The analysis of metabolic biomarkers of target chemicals is
crucial in order to distinguish between internal and external exposure, since
many sources contribute to chemicals being discharged into wastewater. This was
achieved through the employment of a new analytical framework for verification of
biomarkers of exposure to chemicals combining human biomonitoring and water
fingerprinting. Eight EDCs with unknown metabolic pathways (benzophenone-1 (BP
1); benzophenone-2 (BP-2); 4,4'-dihydroxybenzophenone (4,4'-DHBP); 4-benzylphenol
(4-BenzPh); homosalate (HO); octocrylene (OC); 3-benzylidene camphor (3-BC), and
two EDCs with known metabolism (bisphenol A (BPA) and benzophenone-3 (BP-3)) were
tested. The biotransformation observed consisted mainly of phase I processes such
as hydrolysis and hydroxylation together with phase II conjugation reactions such
as sulphation and glucuronidation. Only two chemicals (BP-1, BP-3) were
identified in urine and three chemicals (BPA, BP-1, BP-3) in wastewater. Five
newly discovered metabolites (HO-Met1, OC-Met1, 4-BenzPh-Met4, 4-BenzPh-Met5 and
4-BenzPh-Met6) and one previously known metabolite (BPA-Met3) were detected in
tested urine/wastewater samples from five WWTPs serving large communities ranging
between 17 and 100 thousand inhabitants. The presence of metabolic
biotransformation products of OC, 4-BenzPh, BPA and HO in wastewater provides
evidence for internal exposure of studied populations to these chemicals.
PMID- 29940358
TI - Characterising and modelling free ammonia and ammonium inhibition in anaerobic
systems.
AB - Inhibition by ammoniacal nitrogen, consisting of free ammonia (NH3) and ammonium
ion (NH4+), has been widely investigated for anaerobic digestion. However,
despite the large amount of research on the subject, ammoniacal nitrogen
inhibition still threatens many anaerobic digesters. This paper presents (i) a
method to reliably characterise ammoniacal nitrogen inhibition and (ii) a robust
inhibition modelling approach. Results showed that NH3 and NH4+ inhibition need
to be jointly determined, which can only be done by performing inhibition tests
at various total ammoniacal nitrogen (TAN) concentrations and pH values. These
test conditions were reliably achieved using the salts NH4HCO3 and NH4Cl without
pH adjustment, rather than by using NH4Cl with pH adjustment. The use of only
salts showed a lower pH change during the inhibition test (~1.5 days), thereby
decreasing the uncertainty in TAN speciation and strengthening the test and model
outputs. A threshold inhibition function satisfactorily described (R2 > 0.99) the
joint inhibition of NH3 and NH4+ on three distinct inocula, and provided a better
description of the inhibition testing results than a non-competitive inhibition
function (R2 ~0.70). The key advantage of the proposed threshold inhibition
function is its capacity to identify the inhibition lower limit (concentration
where inhibition starts; KImin) and upper limit (concentration where inhibition
is complete; KImax). The threshold inhibition function also identifies the 50%
inhibition concentration (KI50) at the midpoint of KImin and KImax. Finally,
experimental and model results show that at pH 7.3-7.7 and TAN concentrations
above 2000 mgN.L-1, both NH3 and NH4+ contribute significantly to overall
inhibition.
PMID- 29940359
TI - Steel slag filter design criteria for phosphorus removal from wastewater in
decentralized applications.
AB - The objective of this project was to develop a novel phosphorus removal system
using steel slag filters applicable in decentralized applications and to propose
design criteria about maintenance needs. Slag exhaustion functions were measured
on 2-3 mm, 3-5 mm, 5-10 mm and 16-23 mm slag. Three steel slag columns with
particle size of 2-3 mm, 3-5 mm and 5-10 mm were fed with the effluent of an
aerated lagoon during 589 days. A barrel reactor test was fed during 365 days
with the effluent of an attached growth aerated biological reactor. The o-PO4
concentration at the effluent of the 2-3 mm and 3-5 mm columns and barrel reactor
test was between 0.04 and 0.3 mg P/L. Particulate phosphorus, however, was
removed by about 50%. The P-Hydroslag model implemented in PHREEQC was
successfully calibrated with data from the column test, and validated with data
from the barrel reactor test. The calibrated model was used to simulate long-term
operation of a slag barrel reactor with two parallel streams of five replaceable
steel slag barrels, with total hydraulic retention time of voids of 15 h. The
system longevity was strongly influenced by the influent alkalinity. The
simulated longevity was 7 years with an influent alkalinity of 50 mg CaCO3/L and
2 years with an influent of 210 mg CaCO3/L. The alkalinity of the steel slag
filter influent was influenced by the type of aquifer supplying drinking water,
the presence of nitrification activity and by the CO2 concentration in the
enriched air of the upstream biological process. Simulated scenarios with partial
barrel replacement (e. g. barrels 1 and 2 out of 5 replaced at frequency of 0.5,
1, 1.5, 2, 2.5, 3, 3.5 or 4 years) increased the system longevity up to 14 years
while slightly increasing the number of barrels needed.
PMID- 29940360
TI - Intermolecular interactions of polysaccharides in membrane fouling during
microfiltration.
AB - Membrane technology has been widely employed for seawater desalination, water and
wastewater reclamation, while membrane fouling still remains as a major
challenge. The polysaccharides in extracellular polymeric substances (EPS) have
been recognized as an important foulant that causes serious membrane fouling,
while the detailed structure of polysaccharides and the intermolecular
interactions between them have not been adequately disclosed. In this study, two
different polysaccharides and their mixtures were used to study the
intermolecular cross-linking of polysaccharides as well as its effects on
membrane fouling. Results demonstrated that the fouling propensities of distinct
polysaccharides were completely different, which was attributed to the different
intermolecular interactions lying in polysaccharides. The cross-linking among
molecules of polysaccharide, regardless of the homogeneity, was found to form
complex networks and determine the effective dimension of polysaccharides.
Depending on the effective dimension of foulants, pore blocking and cake layer
occurred subsequently during filtration processes. In light of this, it
potentially gives new insights into the fouling behaviours by combining the
structure-function knowledge of polysaccharides with their fouling propensity. In
addition, transparent exopolymeric particles (TEP) measurement was found to
provide an intuitionistic evaluation of the complex networks formed from
polysaccharides, so that may act as a good indicator of fouling during membrane
filtration.
PMID- 29940361
TI - Transformation of bisphenol AF and bisphenol S by manganese dioxide and effect of
iodide.
AB - In this work, transformation of bisphenol A (BPA) alternatives bisphenol AF
(BPAF) and bisphenol S (BPS) by manganese dioxide (MnO2) and the effect of iodide
(I-) during these processes were investigated in comparison with BPA for the
first time. These three bisphenols showed appreciable reactivity towards MnO2
with the half-lives of their loss following the order of BPA < BPAF < BPS under
similar conditions, and a higher transformation efficiency was generally obtained
at a lower pH. The presence of I- apparently accelerated the transformation of
BPAF and BPS by MnO2 at pH <= 7 but negligibly affected BPA transformation over
the pH range of 5-9. This discrepancy could be well explained by the relative
contribution of hypoiodous acid (HOI) in situ formed from I- oxidation by MnO2.
Polymers, hydroxylated derivatives, and bond-cleavage products were detected from
BPAF and BPS treated by MnO2, where a series of reactions of BPAF/BPS radicals
formed from one-electron oxidation of BPAF/BPS were likely involved, similar to
the case of BPA reported in literature. A group of iodinated aromatic products
were additionally identified from BPAF/BPS treated by MnO2 in the presence of I-
(e.g., iodinated BPAF/BPS and iodinated BPAF/BPS dimers), and they could be
further transformed. This study suggests that naturally occurring manganese
oxides play a significant role in the attenuation of bisphenols released into the
environment and the presence of I- can display a great effect on their
transformation.
PMID- 29940362
TI - Evaluation of a novel quorum quenching strain for MBR biofouling mitigation.
AB - Membrane biofouling, due to Soluble Microbial Products (SMP) and Extracellular
Polymeric Substances (EPS) deposition, results in reduction of the performance of
Membrane Bioreactors (MBRs). However, recently, a new method of biofouling
control has been developed, utilizing the interference of the bacterial inter-
and intra-species' communication. Bacteria use Quorum Sensing (QS) to regulate
the production of SMP and EPS. Therefore, disruption of Quorum Sensing (Quorum
Quenching: QQ), by enzymes or microorganisms, may be a simple mean to control
membrane biofouling. In the present study, a novel QQ-bacterium, namely
Lactobacillus sp. SBR04MA, was isolated from municipal wastewater sludge and its
ability to mitigate biofouling was evaluated by monitoring the changes in
critical flux and transmembrane pressure, along with the production of EPS and
SMP, in a lab-scale MBR system treating synthetic wastewater. Lactobacillus sp.
SBR04MA showed great potential for biofouling control, which was evidenced by the
~3-fold increase in critical flux (8.3 -> 24.25 L/m2/h), as well as by reduction
of the SMP and EPS production, which was lower during the QQ-period when compared
against the control period. Furthermore, the addition of the QQ-strain did not
affect the COD removal rate. Results suggested that Lactobacillus sp. SBR04MA
represents a novel and promising strain for biofouling mitigation and enhancement
of MBRs performance.
PMID- 29940363
TI - Flow-cytometric quantification of microbial cells on sand from water biofilters.
AB - Rapid quantification of absolute microbial cell abundances is important for a
comprehensive interpretation of microbiome surveys and crucial to support
theoretical modelling and the design of engineered systems. In this paper, we
propose a protocol specifically optimised for the quantification of microbial
abundances in water biofilters using flow cytometry (FCM). We optimised cell
detachment from sand biofilter particles for FCM quantification through the
evaluation of five chemical dispersants (NaCl, Triton-X100, CaCl2, sodium
pyrophosphate (PP), Tween 80 combined with PP), different mechanical pre
treatments (low and high energy sonication and shaking) and two fixation methods
(glutaraldehyde and ethanol). The developed protocol was cross-compared using
other established and commonly employed methods for biomass quantification in
water filter samples (adenosine triphosphate (ATP) quantification, real-time
quantitative PCR (qPCR) and volatile solids (VS)). The highest microbial count
was obtained by detaching the biofilm from biofilter grains and dispersing
clusters into singles cells using Tween 80 and sodium pyrophosphate combined with
four steps of high energy sonication (27W, for 80 s each step); glutaraldehyde
was shown to be the best fixative solution. The developed protocol was reliable
and highly reproducible and produced results that are comparable to data from
alternative quantification methods. Indeed, high correlations were found with
trends obtained through ATP and qPCR (rho = 0.98 and rho = 0.91) measurements.
The VS content was confirmed as an inaccurate method to express biomass in sand
samples since it correlated poorly with all the other three methods (rho = 0.005
with FCM, 0.002 with ATP and 0.177 with qPCR). FCM and ATP showed the strongest
agreement between absolute counts with a slope of the correlation equal to 0.7,
while qPCR seemed to overestimate cell counts by a factor of ten. The rapidity
and reproducibility of the method developed make its application ideal for
routine quantification of microbial cell abundances on sand from water biofilters
and thus useful in revealing the ecological patterns and quantifying the
metabolic kinetics involved in such systems.
PMID- 29940364
TI - Four release tests exhibit variable silver stability from nanoparticle-modified
reverse osmosis membranes.
AB - Modification of polyamide reverse osmosis (RO) membranes with silver
nanoparticles (AgNP) may effectively control biofouling. While silver leaching
tests are usually performed during membrane development, the lack of common
testing protocols limits cross-comparison among different labs. We compare four
release tests to quantify the release of dissolved and nanoparticulate silver
from polyamide RO membranes prepared through in situ surface functionalization:
(1) batch immersion, (2) dead-end filtration, (3) cross-flow filtration, and (4)
low-pressure water jetting. For the first time, we demonstrated the possibility
of AgNP release to membrane-treated water through direct AgNP detachment. When
using Nanopure water as an extraction solution, water jetting resulted in the
fastest silver mass release, while dead-end filtration caused the slowest release
based on the initial release kinetic data. Dead-end filtration exhibited silver
mass release an order of magnitude lower than the other three tests. Although
cross-flow filtration may best represent the RO membrane operation, quantifying
silver release suffers from poor mass balance due to the adsorption of dissolved
silver by various reactor components and large volumes of water usage. A commonly
applied batch immersion method was low cost and easily performed, but may not
induce hydraulic shear sufficient for AgNP detachment from a RO membrane. The
information on silver release behavior may depend on the specific test, which is
important for assessing antimicrobial efficacy and service life of the
nanoparticle-functionalized membranes.
PMID- 29940365
TI - Efficient removal of nickel(II) from high salinity wastewater by a novel PAA/ZIF
8/PVDF hybrid ultrafiltration membrane.
AB - Enhanced removal of trace toxic metals (ppm level) from high-salinity wastewater
is crucial to ensure water safety but still a challenging task. In this study, we
fabricated a new hybrid ultrafiltration membrane (PAA/ZIF-8/PVDF) by immobilizing
zeolitic imidazolate framework-8 (ZIF-8) particles onto the surface of trimesoyl
chloride (TMC)-modified polyvinylidene fluoride (PVDF) membrane under protection
of polyacrylic acid (PAA) layer. The resultant PAA/ZIF-8/PVDF membrane exhibited
relatively high water flux of 460 L.m-2 h-1 and outstanding nickel ion (Ni(II))
capacity (219.09 mg/g) from a synthetic high-salinity ([Na+] = 15000 mg/L)
wastewater. X-ray photoelectron spectroscopic studies revealed that preferable
Ni(II) uptake was mainly attributed to the specific interaction between Ni(II)
and hydroxyl groups on ZIF-8 frameworks and carboxyl groups in PAA layer as well.
Compared to PAA, ZIF-8 could selectively bind Ni(II) with negligible effect
exerted by concentrated sodium ion. The filtration study showed that the 12.56
cm2 membrane could effectively treat 5.76 L high-salinity wastewater ([Ni(II)0 =
2 mg/L, [Na+]0 = 15000 mg/L) to conspicuously reduce Ni(II) below the maximum
contaminant level of China, 0.1 mg/L. Moreover, the hybrid membrane could be
regenerated by HCl-NaCl solution (pH = 5.5) for repeated use under direct current
electric field. Generally speaking, the newly developed ZIF-8 hybrid
ultrafiltration membrane showed a very promising potential in enhanced removal of
toxic metals from high-salinity wastewater treatment.
PMID- 29940366
TI - Nitrite accumulation inside sludge flocs significantly influencing nitrous oxide
production by ammonium-oxidizing bacteria.
AB - This work aims to clarify the role of potential nitrite (NO2-) accumulation
inside sludge flocs in N2O production by ammonium-oxidizing bacteria (AOB) at
different dissolved oxygen (DO) levels with focus on the conditions of no
significant bulk NO2- accumulation (<0.2 mg N/L). To this end, an augmented
nitrifying sludge with much higher abundance of nitrite-oxidizing bacteria (NOB)
than AOB was enriched and then used for systematically designed batch tests,
which targeted a range of DO levels from 0 to 3.0 mg O2/L at a fixed ammonium
concentration of 10 mg N/L. A two-pathway N2O model was applied to facilitate the
interpretation of batch experimental data, thus shedding light on the
relationships between N2O production pathways and key process parameters (i.e.,
DO and NO2- accumulation inside sludge flocs). The results demonstrated (i) the
biomass specific N2O production rate firstly increased and then decreased with
DO, with the maximum value of 3.03 +/- 0.05 mg N/h/g VSS obtained at DO level of
0.75 mg O2/L, (ii) the AOB denitrification pathway for N2O production was
dominant (98.0%) at all DO levels tested even without significant bulk NO2-
accumulation (<0.2 mg N/L) observed in the system, but its contribution decreased
with DO, (iii) DO had a positive impact on the hydroxylamine pathway for N2O
production which therefore increased with DO, and (iv) the nitrite accumulation
existed inside the sludge flocs and induced significant N2O production from the
AOB denitrification pathway.
PMID- 29940367
TI - Responsive antimicrobial dental adhesive based on drug-silica co-assembled
particles.
AB - : Most dental resin composite restorations are replacements for failing
restorations. Degradation of the restoration-tooth margins by cariogenic bacteria
results in recurrent caries, a leading cause for restoration failure.
Incorporating antimicrobial agents in dental adhesives could reduce interfacial
bacterial count and reduce recurrent caries rates, inhibit interfacial
degradation, and prolong restoration service life, while minimizing systemic
exposure. Direct addition of antimicrobial compounds into restorative materials
have limited release periods and could affect the integrity of the material.
Attempts to incorporate antimicrobial within mesoporous silica nanoparticles
showed theoretical promise due to their physical robustness and large available
internal volume, yet yielded short-term burst release and limited therapeutic
payload. We have developed novel broad-spectrum antimicrobial drug-silica
particles co-assembled for long-term release and high payload incorporated into
dental adhesives. The release of the drug, octenidine dihydrochloride, is
modulated by the oral degradative environment and mathematically modeled to
predict effective service life. Steady-state release kills cariogenic bacteria,
preventing biofilm formation over the adhesive surface, with no toxicity. This
novel material could extend dental restoration service life and may be applied to
other long-term medical device-tissue interfaces for responsive drug release upon
bacterial infection. STATEMENT OF SIGNIFICANCE: This study describes a novel
dental adhesive that includes a broad-spectrum antimicrobial drug-silica co
assembled particles for long-term antimicrobial effect. The release of the drug,
octenidine dihydrochloride, is modulated by the oral degradative environment and
mathematically modeled to predict effective release throughout the service life
of the restoration. Steady-state drug-release kills caries-forming bacteria,
preventing biofilm formation over the adhesive surface, without toxicity. This
novel material could extend dental restoration service life and may be applied to
other long-term medical device-tissue interfaces for responsive drug release upon
bacterial infection. Since recurrent cavities (caries) caused by bacteria are the
major reason for dental filling failure, this development represents a
significant contribution to the biomaterials field in methodology and material
performance.
PMID- 29940368
TI - Templated dentin formation by dental pulp stem cells on banded collagen bundles
nucleated on electrospun poly (4-vinyl pyridine) fibers in vitro.
AB - : Eventhough it is well established that materials can promote stem cell
differentiation, hard tissue formation is a templated process for which little is
known regarding the in vitro process. We have found that surface curvature
enables self-assembly of triple helical collagen fibrils into banded bundle
structures from rat tail and human collagen secreted by dental pulp stem cells.
Collagen fibrils were adsorbed at 4 degrees C on spun cast flat P4VP films and
electrospun fibers. Protein adsorption was observed on both surfaces, but large
banded bundles with a uniform spacing of approximately 55 nm were present only on
the fiber surfaces. SEM/EDS mapping showed that dental pulp stem cells plated on
the same surfaces biomineralized copiously only along the electrospun fibers.
Raman spectroscopy indicated that despite the presence of adsorbed collagen on
the flat surfaces, only the deposits present on the fibrous surface had a protein
to hydroxyl apatite ratio similar to natural dentin from human teeth. RT-PCR
indicated up regulation of collagen, osteocalcin and dental sialophosphate
protein, confirming that odontogenic differentiation is promoted only on the
fiber scaffolds. Taken together the results indicate that, in addition to surface
chemistry, the supermolecular structure of ECM collagen, which is essential in
directing DPSCs differentiation and templating biomineralization, can be modified
by the underlying surface morphology. STATEMENT OF SIGNIFICANCE: The past decade
has been focused efforts in the use of dental pulp stem cells (DPSC) for dental
regeneration. Eventhough the factors required for DPSCs differentiation have been
well studied, actual mineral deposition, positively identified as dentin, has not
been achieved in vitro. Hard tissue is known to be a templated process in vivo
where the mineral to protein ratio is tightly controlled via proteins which aid
in collagen conformation and mineral sequestration. Here we show that one can
mimic this process in vitro via the combination of materials selection and
morphology. The material chemistry is shown to induce genetic upregulation the
genes responsible for collagen and osteocalcin, while Raman spectroscopy confirms
the translation and adsorption the proteins on the substrate. But, we show that
the simple presence of collagen is not enough to template actual biomineral
deposition similar to that found in vivo. Mineral deposition is a complicated
process templated on collagen bundles and mediated by specific sibling proteins
that determine the protein to mineral ratio. Here we show that surface curvature
can reduce the barrier to collagen bundle formation, directing DPSC
differentiation along odontogenic lineage, and subsequently templating actual
dentin, comparable to that found in vivo in human teeth.
PMID- 29940369
TI - Kinetics of dopamine release from poly(aspartamide)-based prodrugs.
AB - : Preparation of novel biocompatible and biodegradable polymer-based prodrugs
that can be applied in complex drug delivery systems is one of the most
researched fields in pharmaceutics. The kinetics of the drug release strongly
depends on the physicochemical parameters of prodrugs as well as environmental
properties, therefore precise kinetical description is crucial to design the
appropriate polymer prodrug formula. The aim of the present study was to
investigate the dopamine release from different poly(aspartamide) based dopamine
drug conjugates in different environments and to work out a kinetic description
which can be extended to describe drug release in similar systems.
Poly(aspartamide) was conjugated with different amounts of dopamine. In order to
alter the solubility of the conjugates, 2-aminoethanol was also grafted to the
main chain. Chemical structure as well as physical properties such as solubility,
lipophilicity measurements and thermogravimetric analysis has been carried out.
Kinetics of dopamine release from the macromolecular prodrugs which has good
water solubility has been studied and compared in different environments
(phosphate buffer, Bromelain and alpha-Chymotrypsin). It was found that the
kinetics of release in those solutions can be satisfactorily described by first
order reaction rate. For poorly-soluble conjugates, the release of dopamine was
considered as a result of coupling of diffusion and chemical reaction. Besides
the time dependence of dopamine cleavage, a practical quantity, the half-life of
the release of loading capacity has been introduced and evaluated. It was found,
that dopamine containing macromolecular prodrugs exhibit prolonged release
kinetics and the quantitative description of the kinetics, including the most
important physical parameters provides a solid base for future pharmaceutical and
medical studies. STATEMENT OF SIGNIFICANCE: Poly(aspartamide) based polymer-drug
conjugates are promising for controlled and prolonged drug delivery due to their
biocompatibility and biodegradability. In this study different poly(aspartamide)
based dopamine conjugates were synthesized which can protect dopamine from
deactivation in the human body. Since there is no satisfying kinetics description
for drug release from covalent polymer-drug conjugates in the literature,
dopamine release was investigated in different environments and a complete
kinetical description was worked out. This study demonstrates that
poly(aspartamide) is able to protect conjugated dopamine from deactivation and
provide prolonged release in alkaline pH as well as in the presence of different
enzymes. Furthermore, detailed kinetical descriptions were demonstrated which can
be used in case of other covalent polymer-drug conjugates.
PMID- 29940372
TI - The Primo Vascular System as a possible exosomal route across the body:
implications for tumour proliferation and metastasis.
AB - This literature study paper will present the possibility of a correlation between
the Energy Meridians of Traditional Chinese Medicine (TCM), which can be traced
back to the recently described Primo Vessels (formerly known as Bong-Han ducts),
their composition and the ability of tumours to proliferate and metastasise. It
is proposed that microvesicular bodies such as exosomes, known to be involved in
cell-to-cell communication, immune response and tumour proliferation, could be
moving across the body via the Primo Vascular System. The ubiquity of the Primo
Vascular System and its penetration through the blood-brain barrier could also
explain the ability of some peripheral tumours (e.g. breast tumour) to
metastasise in the brain.
PMID- 29940371
TI - Suppressing mesenchymal stem cell hypertrophy and endochondral ossification in 3D
cartilage regeneration with nanofibrous poly(l-lactic acid) scaffold and matrilin
3.
AB - : Articular cartilage has a very limited ability to self-heal after injury or
degeneration due to its low cellularity, poor proliferative activity, and
avascular nature. Current clinical options are able to alleviate patient
suffering, but cannot sufficiently regenerate the lost tissue. Biomimetic
scaffolds that recapitulate the important features of the extracellular matrix
(ECM) of cartilage are hypothesized to be advantageous in supporting cell growth,
chondrogenic differentiation, and integration of regenerated cartilage with
native cartilage, ultimately restoring the injured tissue to its normal function.
It remains a challenge to support and maintain articular cartilage regenerated by
bone marrow-derived mesenchymal stem cells (BMSCs), which are prone to
hypertrophy and endochondral ossification after implantation in vivo. In the
present work, a nanofibrous poly(l-lactic acid) (NF PLLA) scaffold developed by
our group was utilized because of the desired highly porous structure, high
interconnectivity, and collagen-like NF architecture to support rabbit BMSCs for
articular cartilage regeneration. We further hypothesized that matrilin-3
(MATN3), a non-collagenous, cartilage-specific ECM protein, would enhance the
microenvironment of the NF PLLA scaffold for cartilage regeneration and maintain
the cartilage property. To test this hypothesis, we seeded BMSCs on the NF PLLA
scaffold with or without MATN3. We found that MATN3 suppresses hypertrophy in
this 3D culture system in vitro. Subcutaneous implantation of the chondrogenic
cell/scaffold constructs in a nude mouse model showed that pretreatment with
MATN3 was able to maintain chondrogenesis and prevent hypertrophy and
endochondral ossification in vivo. These results demonstrate that the porous NF
PLLA scaffold treated with MATN3 represents an advantageous 3D microenvironment
for cartilage regeneration and phenotype maintenance, and is a promising strategy
for articular cartilage repair. STATEMENT OF SIGNIFICANCE: Articular cartilage
defects, caused by trauma, inflammation, or joint instability, may ultimately
lead to debilitating pain and disability. Bone marrow-derived mesenchymal stem
cells (BMSCs) are an attractive cell source for articular cartilage tissue
engineering. However, chondrogenic induction of BMSCs is often accompanied by
undesired hypertrophy, which can lead to calcification and ultimately damage the
cartilage. Therefore, a therapy to prevent hypertrophy and endochondral
ossification is of paramount importance to adequately regenerate articular
cartilage. We hypothesized that MATN3 (a non-collagenous ECM protein expressed
exclusively in cartilage) may improve regeneration of articular cartilage with
BMSCs by maintaining chondrogenesis and preventing hypertrophic transition in an
ECM mimicking nanofibrous scaffold. Our results showed that the administration of
MATN3 to the cell/nanofibrous scaffold constructs favorably maintained
chondrogenesis and prevented hypertrophy/endochondral ossification in the
chondrogenic constructs in vitro and in vivo. The combination of nanofibrous PLLA
scaffolds and MATN3 treatment provides a very promising strategy to generate
chondrogenic grafts with phenotypic stability for articular cartilage repair.
PMID- 29940373
TI - The measurement of both carotid intima-media thickness and epicardial adipose
tissue thickness in children with epilepsy receiving antiepileptic drug therapy.
AB - OBJECTIVE: The aim of this study was to evaluate the carotid intima-media
thickness together with the thickness of the epicardial adipose tissue in
patients receiving antiepileptic drug therapy and to investigate the presence of
increased cardiovascular risk in these patients. METHODS: The study included a
total of 52 patients comprising 32 males and 20 females who were diagnosed as
having epilepsy and who were using one or more antiepileptic drugs. The control
group consisted of 34 healthy individuals comprising 16 males and 18 females. The
individuals selected for the study group were requested to go to the hospital
after overnight fasting. After blood sampling for serum lipid value, the carotid
intima-media thickness was measured with high resolution B-mode ultrasonography
and epicardial adipose tissue thickness with echocardiography in the patients and
the control group subjects. RESULTS: The carotid intima-media thickness was
determined as 0.47 +/- 0.05 mm in the patient group and 0.44 +/- 0.04 mm in the
control group (p = 0.028). The carotid intima-media thickness was measured as
0.45 +/- 0.05 mm in patients with epilepsy taking monotherapy and 0.49 +/- 0.04
mm in those taking polytherapy (p = 0.003). The epicardial adipose tissue
thickness was determined as 3.42 +/- 0.09 mm in the patient group and 1.72 +/-
0.90 mm in the control group (p = 0.000). The epicardial adipose tissue thickness
was measured as 3.16 +/- 0.87 mm in patients with epilepsy taking monotherapy and
3.77 +/- 0.83 mm in those taking polytherapy (p = 0.041). CONCLUSIONS: It was
determined that carotid intima-media thickness and epicardial adipose tissue
thickness were significantly high in children with epilepsy taking long-term
antiepileptic drugs. These results demonstrate that these patients could be at
increased risk of the development of cardiovascular complications. There is a
need for more extensive studies on this subject.
PMID- 29940370
TI - alpha-Galactosylceramide and peptide-based nano-vaccine synergistically induced a
strong tumor suppressive effect in melanoma.
AB - : alpha-Galactosylceramide (GalCer) is a glycolipid widely known as an activator
of Natural killer T (NKT) cells, constituting a promising adjuvant against
cancer, including melanoma. However, limited clinical outcomes have been obtained
so far. This study evaluated the synergy between GalCer and major
histocompatibility complex (MHC) class I and MHC class II melanoma-associated
peptide antigens and the Toll-Like Receptor (TLR) ligands CpG and monophosphoryl
lipid A (MPLA), which we intended to maximize following their co-delivery by a
nanoparticle (NP). This is expected to improve GalCer capture by dendritic cells
(DCs) and subsequent presentation to NKT cells, simultaneously inducing an anti
tumor specific T-cell mediated immunity. The combination of GalCer with melanoma
peptides and TLR ligands successfully restrained tumor growth. The tumor volume
in these animals was 5-fold lower than the ones presented by mice immunized with
NPs not containing GalCer. However, tumor growth was controlled at similar levels
by GalCer entrapped or in its soluble form, when mixed with antigens and TLR
ligands. Those two groups showed an improved infiltration of T lymphocytes into
the tumor, but only GalCer-loaded nano-vaccine induced a prominent and enhanced
infiltration of NKT and NK cells. In addition, splenocytes of these animals
secreted levels of IFN-gamma and IL-4 at least 1.5-fold and 2-fold higher,
respectively, than those treated with the mixture of antigens and adjuvants in
solution. Overall, the combined delivery of the NKT agonist with TLR ligands and
melanoma antigens via this multivalent nano-vaccine displayed a synergistic anti
tumor immune-mediated efficacy in B16F10 melanoma mouse model. STATEMENT OF
SIGNIFICANCE: Combination of alpha-galactosylceramide (GalCer), a Natural Killer
T (NKT) cell agonist, with melanoma-associated antigens presented by MHC class I
(Melan-A:26) and MHC class II (gp100:44) molecules, and Toll-like Receptor (TLR)
ligands (MPLA and CpG), within nanoparticle matrix induced a prominent anti-tumor
immune response able to restrict melanoma growth. An enhanced infiltration of NKT
and NK cells into tumor site was only achieved when the combination GalCer,
antigens and TLR ligands were co-delivered by the nanovaccine.
PMID- 29940374
TI - Panic and epilepsy in adults: A systematic review.
AB - The purpose of the current paper was to review the empirical literature on the
cooccurrence of panic and epilepsy, in order to determine whether there is an
increased risk of panic attacks and panic disorder among adults with epilepsy and
an increased risk of epilepsy among adults with panic disorder. Given the overlap
between panic and ictal fear, a preliminary aim of the current review was to
critically evaluate the methodology used to differentiate between diagnoses of
panic disorder and epilepsy in existing research. A literature search was
conducted in relevant electronic databases, and articles that directly focused on
panic and epilepsy among adults were selected for the current review (n = 17).
Overall, results suggest that rates of epilepsy are elevated among individuals
with panic disorder and that panic attacks are elevated among individuals with
epilepsy, but rates of panic disorder among people with epilepsy are
inconsistent. However, most studies did not use sufficiently rigorous methods to
differentiate between panic disorder and epilepsy. Therefore, a critical next
step in this area of research is to develop a standard procedure for
differentiating ictal fear from panic attacks and panic disorder.
PMID- 29940375
TI - Effects of valproate on reproductive endocrine function in male patients with
epilepsy: A systematic review and meta-analysis.
AB - BACKGROUND: Valproate (VPA) is a broad spectrum antiepileptic drug (AED) that is
generally used as a first line agent for most idiopathic and symptomatic
generalized epilepsies. Many studies have indicated that AEDs cause reproductive
endocrine disorders in males, but the exact etiology underpinning these
dysfunctions is not clear. This meta-analysis and systematic review was intended
to evaluate the effect of VPA on reproductive endocrine function in male patients
with epilepsy. METHODS: A literature search was performed using electronic
databases up to December 2017 for eligible studies. The differences in the levels
of the reproductive factors, luteinizing hormone (LH), follicle-stimulating
hormone (FSH), sex hormone binding globulin (SHBG), testosterone,
dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ADION) in the male
patients with epilepsy treated with VPA (treatment group) were compared with the
those of the healthy controls (control group) by the use of the Standardized mean
difference (SMD) with 95% confidence intervals (CIs). RESULTS: Six publications
with a total of 316 subjects were identified. The result revealed that the levels
of FSH (SMD = -1.33, 95% CI: -2.60 to -0.07, P = 0.039) and testosterone (SMD =
0.45, 95% CI: -0.87 to -0.03, P = 0.038) of the treatment group were decreased
significantly compared with the healthy controls. There was an increase in the
levels of SHBG (SMD = 0.41, 95% CI: -0.21 to 1.03, P = 0.197), DHEAS (SMD = 0.20,
95% CI: -0.06 to 0.45, P = 0.126) and ADION (SMD = 0.73, 95% CI: -0.10 to 1.57, P
= 0.086), and a decrease in that of LH(SMD = -0.71, 95% CI: -1.49 to 0.07, P =
0.075) in the male patients with epilepsy treated with VPA, but the differences
did not reach statistical significance (P > 0.05). CONCLUSIONS: This meta
analysis indicates that VPA may lead to a significant decrease in the levels of
FSH and testosterone and alter the concentrations of LH, DHEAS, SHBG, and ADION
to some extent, which might contribute to the reproductive endocrine dysfunction
in male patients with epilepsy. It is important for clinical neurologists to be
cautious when prescribing VPA to reproductive-aged male patients with epilepsy.
PMID- 29940376
TI - Intellectual outcome after a cortical lesion with versus without epilepsy: A life
span neurodevelopmental view.
AB - : In patients with cortical lesions, the structure of intelligence has never been
studied as a function of age at lesion onset and presence vs absence of lesional
epilepsy over the life span. METHOD: Two thousand one hundred eighty-six cases
were assembled bearing unilateral cortical lesions occurring at all ages (1301
with seizures) with postlesion verbal intelligence quotient (IQ) (VIQ) and
performance IQ (PIQ). RESULTS: Global IQ significantly and constantly decreased
as a function of age at lesion onset in the cases without epilepsy, and increased
in the cases with epilepsy. Beyond the lesion onset age of 12 years, VIQ was
significantly higher than PIQ in the cases without epilepsy, and lower in the
cases with epilepsy. The VIQ/PIQ * lesion-side interaction indicative of
hemispheric specialization increased significantly linearly with age at lesion
onset in the patients without epilepsy but ceased to progress at the lesion-onset
age of 30 years and beyond in the cases with epilepsy. CONCLUSION: Postlesion
global IQ, the difference between VIQ and PIQ, and the laterality index all vary
significantly as a function of age at lesion onset. In addition, these changes
over the life span are all quite different between cases with and without
epilepsy.
PMID- 29940377
TI - Wearable technology in epilepsy: The views of patients, caregivers, and
healthcare professionals.
AB - PURPOSE: In recent years, digital technology and wearable devices applied to
seizure detection have progressively become available. In this study, we
investigated the perspectives of people with epilepsy (PWE), caregivers (CG), and
healthcare professionals (HP). We were interested in their current use of digital
technology as well as their willingness to use wearables to monitor seizures. We
also explored the role of factors influencing engagement with technology,
including demographic and clinical characteristics, data confidentiality, need
for technical support, and concerns about strain or increased workload. METHODS:
An online survey drawing on previous data collected via focus groups was
constructed and distributed via a web link. Using logistic regression analyses,
demographic, clinical, and other factors identified to influence engagement with
technology were correlated with reported use and willingness to use digital
technology and wearables for seizure tracking. RESULTS: Eighty-seven surveys were
completed, fifty-two (59.7%) by PWE, 13 (14.4%) by CG, and 22 (25.3%) by HP.
Responders were familiar with multiple digital technologies, including the
Internet, smartphones, and personal computers, and the use of digital services
was similar to the UK average. Moreover, age and disease-related factors did not
influence access to digital technology. The majority of PWE were willing to use a
wearable device for long-term seizure tracking. However, only a limited number of
PWE reported current regular use of wearables, and nonusers attributed their
choice to uncertainty about the usefulness of this technology in epilepsy care.
People with epilepsy envisaged the possibility of understanding their condition
better through wearables and considered, with caution, the option to send
automatic emergency calls. Despite concerns around accuracy, data
confidentiality, and technical support, these factors did not limit PWE's
willingness to use digital technology. Caregivers appeared willing to provide
support to PWE using wearables and perceived a reduction of their workload and
anxiety. Healthcare professionals identified areas of application for digital
technologies in their clinical practice, pending an appropriate reorganization of
the clinical team to share the burden of data reviewing and handling.
CONCLUSIONS: Unlike people who have other chronic health conditions, PWE appeared
not to be at risk of digital exclusion. This study highlighted a great interest
in the use of wearable technology across epilepsy service users, carers, and
healthcare professionals, which was independent of demographic and clinical
factors and outpaced data security and technology usability concerns.
PMID- 29940378
TI - Sexual dysfunction and associated factors in Chinese Han women with epilepsy.
AB - PURPOSE: Women with epilepsy (WWE) are believed to be at risk of sexual
dysfunction (SD) and face many sexual challenges because of multiple factors.
This study aimed to assess the factors associated with SD in Chinese Han WWE.
METHODS: This cross-sectional study examined 112 married WWE in the Affiliated
Hospital of Yangzhou University with focal (FE) or generalized epilepsy (GE) on
antiepileptic drugs (AEDs), and 120 healthy controls without epilepsy, all of
Chinese Han nationality. Data collection tools included the Chinese version of
Female Sexual Function Index (FSFI), the Chinese version of Zung Self-Rating
Anxiety Scale (SAS), the Chinese version of the Zung Self-Rating Depression Scale
(SDS), the Chinese version of the revised Morisky Medication Adherence Scale
(MMAS-8), and the Chinese version of the National Hospital Seizure Severity Scale
(NHS3). Chi-square test, t-test, one-way analysis of variance (ANOVA), and binary
logistic regression were used for statistical analysis. RESULTS: A high rate
(70.5%) of SD was detected in WWE, with 24.2% in controls. Sexual dysfunction
affected all dimensions: desire (85.7%), arousal (56.3%), lubrication (47.3%),
orgasm (66.1%), satisfaction (58.9%), and pain (41.1%). Elevated rates of anxiety
(40.2%) and depression (33%) and poor medication adherence (31.3%) were also
found in WWE. Binary logistic regression found that poor economic status (odds
ratio (OR) = 13.904, 95% confidence interval (CI): 2.025-95.472, P = 0.007 and OR
= 6.350, 95% CI: 1.323-30.477, P = 0.021), anxiety (OR = 1.222, 95% CI: 1.055
1.415, P = 0.007), and poor medication adherence (OR = 0.297, 95% CI: 0.124
0.707, P = 0.006) were associated with SD. CONCLUSIONS: The associated factors of
SD in Chinese Han WWE are multifactorial. The WWE have higher levels of anxiety,
poor family economic status, and poor medication adherence. Medical professionals
should not only better control seizures but also evaluate and improve patients'
sexual function so as to improve the quality of life of WWE.
PMID- 29940379
TI - Spontaneous Regression of an Intraparenchymal Cyst Following Deep Brain
Stimulator Electrode Implantation: Case Report and Literature Review.
AB - BACKGROUND: The development of an intraparenchymal cyst following deep brain
stimulation (DBS) surgery is an uncommon complication that lacks a clearly
defined management strategy. The pathophysiology is not known and may be related
to perielectrode edema or cerebrospinal fluid tracking. Previous case reports
have described various therapies for symptomatic cysts, including hardware
removal or conservative treatment with steroids. CASE DESCRIPTION: We present a
male patient with bilateral DBS of the ventral intermediate nucleus of the
thalamus for management of essential tremor, who developed a cystic cavitation at
the left electrode tip and was followed without treatment. This patient developed
dysarthria, gait impairment, and unilateral motor deficits 3 months after
surgery. Perielectrode edema was initially identified, eventually coalescing into
a cystic cavitation at the electrode tip. Cystic regression and symptomatic
improvement were observed without any surgical or medical intervention, with full
cyst resolution by 17 months. CONCLUSIONS: Only 15 additional cases have been
reported in the literature, although the true incidence may be underreported
because of varying practices in obtaining postoperative scans. Cysts were
identified in symptomatic patients on average 6.2 months after surgery. All
symptomatic cysts were treated with hardware removal or steroid therapy.
Observation alone may be sufficient when a DBS-associated cyst is identified.
More reports are needed to characterize this rare complication.
PMID- 29940380
TI - Positioning-Related Neuromonitoring Change During Anterior Cervical Discectomy
and Fusion.
AB - BACKGROUND: Intraoperative neuromonitoring (ION) signal changes during spine
surgery may portend a potentially catastrophic neurologic injury that, if
identified and addressed expediently, may allow the surgeon to take correction
actively and prevent permanent neurologic injury. CASE DESCRIPTION: We report a
case of transient loss in somatosensory evoked potentials signals during anterior
cervical discectomy and fusion (ACDF) C4-7, which was mainly attributed to
shoulder traction using a special device. The signal loss returned immediately
after the release of should traction. CONCLUSIONS: The use of multimodality ION
is recommended for ACDF with shoulder traction to prevent postoperative
neurologic deficit associated with a position-related injury. Baseline ION should
be established before positioning.
PMID- 29940381
TI - Analysis of Computed Tomography Scan After Anterior Odontoid Screw Fixation with
the Herbert Screw: Is It Effective to Reduce Fracture Gap?
AB - OBJECTIVE: To assess computed tomography scans to evaluate the extent of
reduction of fracture displacement and fracture gap after anterior odontoid screw
fixation using the Herbert screw. METHODS: Thirty-seven odontoid fractures were
reduced and treated by anterior odontoid screw fixation with the Herbert screw.
There were 37 patients whose age ranged from 20 to 79 years. Three-dimensional
computed tomography scans were obtained for all patients to assess the screw
position, the presence of the penetration of superior cortex of dens, the extent
of reduction of fracture displacement, and fracture gap. RESULTS: Mean fracture
displacement was 2.6 +/- 3.2 mm before surgery; after the operation this value
was 1.0 +/- 1.5 mm. The difference in fracture gap between the preoperative and
the postoperative state was -0.1 +/- 1.1 mm, which was not statistically
significant (P = 0.667). We achieved cortical purchase in only 16 of 37 patients
(43.2%); cortical purchase was not obtained in 21 patients (56.7%) due to the
fear of the risk of the damage of neural and vascular structures. Of these 21
patients who had no penetration of the superior cortex of dens, widening of the
fracture gap occurred in 12 patients (57%), no change in 6 patients (29%), and
there was shortening in 3 patients (14%). However, of the 16 patients with
penetration of apical dens tip, we achieved significant reduction of fracture gap
(P = 0.002). CONCLUSIONS: To maximize reduction of fracture gap using the Herbert
screw, it is essential to penetrate the apical dens tip.
PMID- 29940382
TI - Dural Arteriovenous Fistula Between the Inferolateral Trunk and Cavernous Sinus
Draining to Ophthalmic Vein.
AB - BACKGROUND: Formation of a dural arteriovenous fistula (DAVF) between the
inferolateral trunk (ILT) and cavernous sinus (CS) is rare. CASE DESCRIPTION:
This study presents a case of ILT-CS DAVF. A 64-year-old male patient had
exophthalmos of the left eye with redness and swelling. Digital subtraction
angiography revealed a connection between the ILT and the CS that formed a high
flow DAVF, which was drained only to the ophthalmic vein and no other parts of
the CS. The ILT was chosen as the transarterial path for treatment because it was
enlarged. The microcatheter was navigated into the ILT, and 2 coils were then
used to occlude the ILT. After occlusion of the ILT, no image of the DAVF
indicated that the ILT-CS DAVF was completely cured. The patient's symptoms
improved gradually after surgery. At the 6-month follow-up visit, digital
subtraction angiography showed no sign of ILT-CS DAVF and the patient's eye
symptoms had disappeared. CONCLUSIONS: Although ILT-CS DAVF is rare, it can still
be seen in clinical practice. Coiling the ILT via a transarterial approach is a
good option for treatment.
PMID- 29940383
TI - Transforaminal Endoscopic Decompression in the Setting of Lateral Lumbar
Spondylolisthesis.
AB - BACKGROUND: Lateral subluxation of the vertebra is commonly seen in degenerative
lumbar scoliosis. Transforaminal endoscopic spine surgery is an emerging
technique in spine surgery but has never been described as a treatment option for
lumbar radiculopathy in the setting of lateral lumbar spondylolisthesis. METHODS:
A technique for endoscopic treatment of lumbar disc herniation in the setting of
lateral spondylolisthesis is presented. We retrospectively reviewed 199 cases of
patients who underwent transforaminal endoscopic surgery in a 3-year period with
a minimum follow-up of 1 year. RESULTS: Between 2014 and 2017, 4 patients
(average age, 74.8 years; range, 69-82 years) underwent transforaminal endoscopic
discectomy procedures for disc herniations at the level of lateral subluxation.
One patient whose lateral subluxation was above an instrumented fusion required
an extension of fusion to the operated level 5 months after endoscopic surgery
for a reherniation. For the other 3 patients, mean visual analog scale score for
radicular pain improved from an average pain score of 8.3 before surgery to 3.0 1
year after surgery, and Oswestry Disability Index improved from 26.7 to 4.7.
CONCLUSIONS: Transforaminal endoscopic surgery for lumbar disc herniation in the
setting of lateral subluxation of vertebral bodies is a unique minimally invasive
approach for treatment of lumbar radiculopathy that might be considered as an
alternative treatment to deformity correction surgery in older patients.
PMID- 29940384
TI - Fatal Subarachnoid Hemorrhage from an Aneurysm of a Persistent Primitive
Hypoglossal Artery: Case Series and Literature Overview.
AB - BACKGROUND: Persistent carotid-basilar connections have a prevalence of 0.14%.
Recognizing such persistent fetal anastomoses between the carotid and the
vertebrobasilar circulation is of great importance because they are reportedly
associated with an increased prevalence of intracranial aneurysms. METHODS: We
report the case of a 15-year-old female patient who presented with a World
Federation of Neurosurgical Societies grade 5 subarachnoid hemorrhage from an
aneurysm at the junction of a persistent primitive hypoglossal artery and the
posterior inferior cerebellar artery origin. Supratentorially, unfortunately,
there was no parenchymal blush or cortical venous return. Eventually, a
multidisciplinary decision was made to withdraw care. RESULTS: Fifty-seven cases
were reported in the literature to date of persistent hypoglossal arteries, 16 of
which presented with an associated aneurysm, 5 with an arteriovenous
malformation, and 6 with a subarachnoid hemorrhage. Our case is the youngest
patient reported so far. Hypoplasia or aplasia of the vertebral artery often were
encountered (36 and 13 cases, respectively), as well as carotid artery stenosis
(15 cases). CONCLUSIONS: Although uncommon, it is important to recognize
persistent carotid-basilar connections, since they have a considerable
hemodynamic impact on the posterior cerebral circulation via the carotid system.
A critical reduction in the carotid blood flow will, therefore, have ischemic
consequences in the posterior cerebral territories. In addition, such connections
might be associated with anomalies of the vessel wall and be predisposed to
aneurysm formation. The endovascular neurointerventionalist, as well as the
vascular and skull base neurosurgeon, need to be aware of their anatomy and
variations.
PMID- 29940386
TI - Impaired anticipatory vision and visuomotor coordination affects action planning
and execution in children with hemiplegic cerebral palsy.
AB - BACKGROUND: Action-planning and execution deficits in children with hemiplegic
cerebral palsy (HCP) are potentially due to deficits in the integration of
sensory information, such as vision, with motor output. AIMS: To determine
differences in anticipatory visual patterns in children with HCP compared to
typically developing (TD) children, and to assess visuomotor coordination in
children with HCP. METHODS AND PROCEDURES: We included 13 children with HCP (Age
= 6.8 + 2.9 yrs) and 15 TD children (Age = 5.8 + 1.1 yrs). The experimental task
used in this study is a valid action-planning task, which consisted of initially
reaching and grasping an object placed at a fixed position, followed by placing
the object in a random target position. Visual patterns were recorded using a
head-mounted eye-tracker system and arm movements were recorded using motion
capture (120 Hz). OUTCOMES AND RESULTS: Children with HCP had delayed
anticipatory gaze time and longer latency than TD children during the planning
and execution phases. Children with HCP also had a higher frequency of gaze
shifts, longer reaction times (RT) and movement times (MT) than TD children.
CONCLUSIONS AND IMPLICATIONS: Children with HCP may have deficits in anticipatory
vision, which potentially affected planning and executing a goal-directed action.
Therapeutic interventions focusing on improving visuomotor coordination may
improve the motor performance in children with HCP.
PMID- 29940385
TI - Mini-Pterional Craniotomy for Resection of Parasellar Meningiomas.
AB - BACKGROUND: Surgical resection of parasellar meningiomas is a challenging
operation that traditionally has been performed with a large pterional or
orbitozygomatic craniotomy. In this study, we report patient outcomes and detail
our surgical approach when resecting these tumors with a smaller, less invasive
"mini-pterional" craniotomy. METHODS: We performed a retrospective review on all
patients undergoing a mini-pterional craniotomy for resection of parasellar
meningiomas from 2012 to 2016. We describe the technical aspects of the mini
pterional craniotomy and provide the outcomes of patients who received an
operation with this approach. RESULTS: Twenty-four patients were treated with a
mini-pterional craniotomy for resection of parasellar meningiomas. Median tumor
volume was 6.2 cm3. Twenty-two of 24 (92%) patients had a World Health
Organization grade I meningioma, and 2 of 24 (8%) patients had a World Health
Organization grade II meningioma. Tumors were located at the medial sphenoid wing
(60%), anterior clinoid (24%) and spheno-cavernous junction (12%). Nineteen of 24
(79%) patients had a Simpson Grade I resection and 5 of 24 (21%) a Simpson Grade
IV resection. Median length of the operations was 242 minutes. Neurosurgical
complications occurred in 2 patients who had a surgical-site infection and
cerebrospinal fluid leak; one of these patients also developed postoperative
hydrocephalus. In this series, no deaths, parenchymal contusions, or repeat
operations occurred. CONCLUSIONS: The mini-pterional craniotomy can be used to
resect parasellar meningiomas with good results and a low complication profile.
This approach provides an efficacious method of resecting these tumors without
sacrificing Simpson grade or patient safety.
PMID- 29940388
TI - Prescription tranquilizer/sedative misuse prevalence and correlates across age
cohorts in the US.
AB - BACKGROUND: Prescription tranquilizer/sedative (e.g., alprazolam, zolpidem)
misuse (i.e., use in ways not intended by the prescriber or without a
prescription) is understudied, with little research identifying misuse
correlates. Identification of key correlates could identify subgroups more likely
to engage in misuse, allowing for targeted treatment. This work examines
tranquilizer/sedative use and misuse prevalence rates and misuse correlates
across U.S. age cohorts, using nationally representative data. METHODS: Data were
from the 2015-16 National Survey on Drug Use and Health (n = 114,043). Analyses
used design-based logistic regression for past-year tranquilizer/sedative misuse
correlates across participants or those engaged in past-year use; past-month
misuse correlates were also examined in those with past-year misuse. RESULTS:
Young adults (18-25 years) had the highest prevalence of past-year and past-month
tranquilizer/sedative misuse, with 42.8% of those with past-year use also engaged
in misuse. Mental health correlates were associated with past-year misuse, while
substance use, particularly opioid misuse, was associated with both past-year and
past-month misuse. Substance use correlate strength was most likely to vary by
age group, with older adults (65 years and older) having fewer significant
correlates overall. CONCLUSIONS: This work highlighted young adults and those
with other substance use as most likely to engage in tranquilizer/sedative
misuse. In particular, those endorsing suicidality and reporting opioid misuse
are a subgroup of concern, given their especially elevated rates of misuse and
the increased risk for overdose imparted by tranquilizer/sedative medication.
Workplace-based interventions for young adults and school-based universal
prevention may be warranted to limit tranquilizer/sedative misuse in these
groups.
PMID- 29940387
TI - Personal and perceived peer use and attitudes towards use of non-prescribed
prescription sedatives and sleeping pills among university students in seven
European countries.
AB - INTRODUCTION: The use of non-prescribed prescription sedatives and sleeping pills
(NPPSSP) among university students has been described as an important public
health issue. However, the impact of perceived social norms on students' use and
attitudes towards use of NPPSSP is still unclear. Our aim was to investigate
whether perceptions of peer use and approval of use are associated with students'
personal use and approval of NPPSSP use. METHODS: Cross-sectional data from the
Social Norms Intervention for the prevention of Polydrug Use (SNIPE) project
containing 4482 university students from seven European countries were analyzed
to investigate self-other discrepancies regarding personal use and attitudes
towards NPPSSP use. Associations between personal and perceived peer use and
between personal and perceived approval of use were examined using multivariable
logistic regression. RESULTS: The majority (51.0%) of students perceived their
peers' NPPSSP use to be higher than their personal use. 92.6% of students
perceived their peers' approval of NPPSSP use to be identical or higher than
their personal approval. Students perceiving that the majority of peers had used
NPPSSP at least once displayed higher odds for personal lifetime use (OR: 1.95,
95% CI: 1.49-2.55). Perceived peer approval of NPPSSP use was associated with
higher odds for personal approval (OR: 5.49, 95% CI: 4.63-6.51). CONCLUSIONS:
Among European university students, perceiving NPPSSP use and approval of use to
be the norm was positively associated with students' personal NPPSSP use and
approval of use, respectively. Interventions addressing perceived social norms
may prevent or reduce NPPSSP use among university students. Final trial
registration number: DRKS00004375 on the 'German Clinical Trials Register'.
PMID- 29940389
TI - Cigarette smoking duration mediates the association between future thinking and
norepinephrine level.
AB - Fixating on the present moment rather than considering future consequences of
behavior is considered to be a hallmark of drug addiction. As an example,
cigarette smokers devalue delayed consequences to a greater extent than
nonsmokers, and former smokers devalue delayed consequences more than nonsmokers,
but less than current smokers. Further, cigarette smokers have higher
norepinephrine levels than nonsmokers, which is indicative of poor future health
outcomes. It is unclear how duration of cigarette smoking may impact these
associations. The current secondary analysis of publicly available data
investigated whether extent of future thinking is associated with smoking
duration, as well as norepinephrine level, in a large national US sample (N =
985) of current, former, and never smokers. Individuals scoring lower on future
thinking tended to smoke for longer durations and had higher norepinephrine
levels relative to individuals scoring higher on future thinking. In addition,
duration of cigarette abstinence interacted significantly with future thinking
and smoking duration for former smokers. Specifically, the mediation relationship
between future thinking, smoking duration, and norepinephrine level for former
smokers was strongest at shorter durations of cigarette abstinence and decreased
as a function of increasing duration of cigarette abstinence. Overall, results
from this study suggest the potential importance of implementing smoking
cessation treatments as early as possible for smokers and support future thinking
as a potential therapeutic target for smoking cessation treatment.
PMID- 29940390
TI - Exposure to positive peer sentiment about nicotine replacement therapy in an
online smoking cessation community is associated with NRT use.
AB - BACKGROUND: Little is known about the influence of online peer interactions on
health behavior change. This study examined the relationship between exposure to
peer sentiment about nicotine replacement therapy (NRT) in an online social
network for smoking cessation and NRT use. METHODS: Participants were 3297
current smokers who enrolled in an Internet smoking cessation program,
participated in a randomized trial, and completed a 3-month follow-up. Half
received free NRT as part of the trial. Automated text classification identified
27,038 posts about NRT that one or more participants were exposed to in the
social network. Sentiment towards NRT was rated on Amazon Mechanical Turk.
Participants' exposure to peer sentiment about NRT was determined by analysis of
clickstream data. Modified Poisson regression examined self-reported use of NRT
at 3-months as a function of exposure to NRT sentiment, controlling for study arm
and post exposure. RESULTS: One in five participants (19.3%, n = 639) were
exposed to any NRT-related posts (mean exposure = 6.5 +/- 14.7, mean sentiment =
5.4 +/- 0.8). The association between sentiment exposure and NRT use varied by
receipt of free NRT. Greater exposure to positive NRT sentiment was associated
with an increased likelihood of NRT use among participants who did not receive
free NRT (adjusted rate ratio 1.22, 95% CI 1.01, 1.47; p = .043), whereas no such
relationship was observed among participants who did receive free NRT (p = .48).
CONCLUSIONS: Exposure to positive sentiment about NRT was associated with
increased NRT use when smokers obtained it on their own. Highlighting user
generated content containing positive NRT sentiment may increase NRT use among
treatment-seeking smokers.
PMID- 29940391
TI - Consideration of future consequences as a moderator of the willingness-behavior
relationship for young adult marijuana use and consequences.
AB - The Prototype Willingness Model is a dual-processing (i.e., intentional and
socially reactive) health-risk behavior model. The socially reactive path
includes behavioral willingness, descriptive normative perceptions, and favorable
images of individuals who engage in health-risk behavior (prototype favorability)
as important predictors of health behaviors. Individual differences (such as
consideration of future consequences) may potentiate the effects of behavioral
willingness on health-risk outcomes, such as marijuana use. Given limited
research investigating marijuana use and the Prototype Willingness Model, the
goals of the current study were: 1) examine consideration of future consequences
and Prototype Willingness Model social reaction pathway variables in relation to
behavioral willingness to use marijuana longitudinally; and 2) determine if
consideration of future consequences moderated the behavioral willingness
marijuana use relation prospectively. Young adults (N = 769) from a larger
longitudinal study completed baseline and 3 follow-up assessments (Months 3, 4,
5). Behavioral willingness was positively related to a higher likelihood of use,
more days having used marijuana, and more consequences prospectively, over and
above baseline use. Consideration of future consequences moderated the
association between behavioral willingness and hours high in a typical week.
These findings support the willingness-behavior association of the Prototype
Willingness Model and preliminarily demonstrate consideration of future
consequences' differential impact on behavioral willingness-future marijuana use
relation. Intervention and prevention implications are discussed.
PMID- 29940392
TI - Comparative transcriptomics in three Passerida species provides insights into the
evolution of avian mitochondrial complex I.
AB - Recent studies have shown that mitochondria play a crucial role in cellular
energy production through the oxidative phosphorylation (OXPHOS) system. Complex
I (NADH:ubiquinone oxidoreductase), the first and largest enzyme complex of the
OXPHOS system, includes both nuclear- and mitochondrial-encoded proteins.
However, the patterns of natural selection and phylogenetic implications of
complex I in birds still remain unclear. In this study, we combined
transcriptomic and phylogenetic analyses to comprehensively determine the
evolution of avian complex I. The transcriptomes of three Passerida species
(Leiothrix lutea, Spodiopsar sericeus, and Passer montanus) were obtained using
the Illumina HiSeqTM 2500 system. More than 192,000,000 clean reads were
assembled in a total of 828,267 transcripts. Evolutionary selection analysis
suggested that six genes of the core subunits in avian complex I may have
undergone putative positive selection. Notably, we found that the mean dN/dS
(omega) ratio for mitochondrial genes of core subunits was significantly lower
than that for nuclear genes of non-core subunits within complex I. The
constructed maximum-parsimony, maximum-likelihood, and Bayesian inference
phylogenetic trees were based on 44 complex I genes. We verified that the family
Paridae (represented by Parus major and Pseudopodoces humilis) was clustered with
Musicicapoidea. Our results provide new insights into the evolution of avian
mitochondrial complex I.
PMID- 29940393
TI - Transcriptomic analysis of differentially expressed genes in the molting gland (Y
organ) of the blackback land crab, Gecarcinus lateralis, during molt-cycle stage
transitions.
AB - A transcriptome of the Gecarcinus lateralis molting gland (Y-organ or YO)
contained 48,590 contiguous sequences (contigs) from intermolt (IM), early
premolt (EP), mid premolt (MP), late premolt (LP), and postmolt (PM) stages. The
YO is kept in the basal state in IM by molt-inhibiting hormone (MIH)/cyclic
nucleotide-dependent signaling. YO activation in EP requires down-regulation of
MIH signaling and activation of mechanistic target of rapamycin (mTOR)-dependent
protein synthesis. Transition of the YO to the committed state in MP requires
activin/transforming growth factor-beta (TGFbeta) signaling. YO repression occurs
at the end of LP. A total of 28,179 contigs (58%) showed molt stage-specific
changes in gene expression. The largest number of differentially-expressed genes
(DEGs) were at the IM/EP (16,142 contigs), LP/PM (18,161 contigs), and PM/IM
(8290 contigs) transitions. By contrast, the numbers of DEGs were 372 and 1502
contigs for the EP/MP and MP/LP transitions, respectively. DEG analysis of 23
signal transduction pathways showed significant changes in MIH, mTOR,
activin/TGFbeta, Notch, MAP kinase, and Wnt signaling. Down-regulation of MIH
signaling genes in premolt is consistent with reduced MIH sensitivity in MP and
LP. Up-regulation of mTOR signaling genes in IM and premolt stages is consistent
with its role in YO activation and sustained ecdysteroidogenesis. Up-regulation
of activin/TGFbeta signaling genes in EP and MP is consistent with the role of a
myostatin/activin-like factor in YO commitment. Notch, MAP kinase, and Wnt DEG
analysis may indicate possible crosstalk with the MIH, mTOR, and activin/TGFbeta
pathways to integrate other inputs to control YO ecdysteroidogenesis.
PMID- 29940394
TI - Effect of ply orientation and through-thickness position of delamination on the
reflection of fundamental symmetric S0 Lamb mode in GFRP composite plate
structures.
AB - This paper studies the interaction of the fundamental symmetric Lamb wave mode S0
with delaminations in 8-layered glass fibre reinforced polymer (GFRP) laminated
composites, using numerical models validated against experiments. The validation
is performed using experiments on the eight layer quasi-isotropic GFRP composite
laminate [0/90/45/-45]S. Further numerical studies were performed on the
laminates [0/45/-45/90]S, [0/45/90/-45]S, [90/45/-45/0]S, [90/-45/0/45]S, [45/
45/0/90]S, and [45/90/-45/0]S to study the effect of ply layups on the reflection
of S0 Lamb waves. The reflection coefficients calculated for these laminates
followed a similar trend as the laminate [0/90/45/-45]S. Physical insight was
obtained into the reflection behaviour, based on an analysis of wave dispersion
in the sub-laminates. It was difficult to detect the delamination situated at the
mid plane of the laminate, where the shear stress was found to be zero for all
ply layups. The delaminations present at a depth greater than DL12 (>0.42 mm)
from the source of excitation, were found to be accessible for the laminates
[0/90/45/-45]S, [0/45/-45/90]S and [0/45/90/-45]S. The sensitivity of the S0 mode
reflection depends upon the position of the delamination along the thickness
direction and ply layup orientation of the composite laminate. The S0 mode showed
higher sensitivity to DL23 and DL34 (0.42 mm to 1.26 mm) in all the laminates
that were inspected.
PMID- 29940395
TI - Surface acoustic waves in one-dimensional piezoelectric-metallic phononic
crystal: Effect of a cap layer.
AB - We study the propagation of transverse acoustic waves associated with the surface
of a semi-infinite superlattice (SL) composed of piezoelectric-metallic layers
and capped with a piezoelectric layer. We present closed-form expressions for
localized surface waves, the so-called Bleustein-Gulyaev (BG) waves depending on
whether the cap layer is open-circuited or short-circuited. These expressions are
obtained by means of the Green's function method which enables to deduce also the
densities of states. These theoretical results are illustrated by a few numerical
applications to SLs made of piezoelectric layers of hexagonal symmetry belonging
to the 6 mm class such as PZT4 and ZnO in contact with metallic layers such as
Fe, Al, Au, Cu and boron-doped-diamond. We demonstrate a rule about the existence
of surface modes when considering two complementary semi-infinite SLs obtained by
the cleavage of an infinite SL along a plane parallel to the piezoelectric
layers. Indeed, when the surface layers are open-circuited, one obtains one
surface mode per gap, this mode is associated with one of the two complementary
SLs. However, when the surface layers are short-circuited, this rule is not
fulfilled and one can obtain zero, one or two modes inside each gap of the two
complementary SLs depending on the position of the plane where the cleavage is
produced. We show that in addition to the BG surface waves localized at the
surface of the cap layer, there may exist true guided waves and pseudo-guided
waves (i.e. leaky waves) induced by the cap layer either inside the gaps or
inside the bands of the SL respectively. Also, we highlight the possibility of
existence of interface modes between the SL and a cap layer as well as an
interaction between these modes and the BG surface mode when both modes fall in
the same band gaps of the SL. The strength of the interaction depends on the
width of the cap layer. Finally, we show that the electromechanical coupling
coefficient (ECC) is very sensitive to the cap layer thickness, in particular we
calculate and discuss the behavior of the ECC as a function of the adlayer
thickness for the low velocity surface modes of the SL which exhibit the highest
ECC values. The effect of the nature of the metallic layers inside the SL on the
ECC is also investigated. The different surface modes discussed in this work
should have applications in sensing applications.
PMID- 29940396
TI - Nonlinear effects of micro-cracks on long-wavelength symmetric Lamb waves.
AB - For an elastic medium containing a homogeneous distribution of micro-cracks, an
effective one-dimensional stress-strain relation has been determined with finite
element simulations. In addition to flat micro-cracks, voids were considered that
contain a Hertzian contact, which represents an example for micro-cracks with
internal structure. The orientation of both types of micro-cracks was fully
aligned or, for flat micro-cracks, totally random. For micro-cracks with Hertzian
contacts, the case of random orientation was treated in an approximate way. The
two types of defects were found to give rise to different degrees of non-analytic
behavior of the effective stress-strain relation, which governs the nonlinear
propagation of symmetric (S0) Lamb waves in the long-wavelength limit. The
presence of flat micro-cracks causes even harmonics to grow linearly with
propagation distance with amplitudes proportional to the amplitude of the
fundamental wave, and gives rise to a static strain. The presence of the second
type of defects leads to a linear growth of all harmonics with amplitudes
proportional to the power 3/2 of the fundamental amplitude, and to a strain
dependent velocity shift. Simple expressions are given for the growth rates of
higher harmonics of S0 Lamb waves in terms of the parameters occurring in the
effective stress-strain relation. They have partly been determined quantitatively
with the help of the FEM results for different micro-crack concentrations.
PMID- 29940397
TI - Conformations of Neisseria meningitidis serogroup A and X polysaccharides: The
effects of chain length and O-acetylation.
AB - Neisseria meningitidis is a major cause of bacterial meningitis worldwide
especially in Africa. The capsular polysaccharide (CPS) is the main virulence
factor and the target antigen for polysaccharide and conjugate vaccines. The high
burden of serogroup A disease in the Meningitis Belt of sub-Saharan Africa led to
the introduction of MenAfriVac(r), which has successfully reduced the number of
cases of group A disease. However, several outbreaks caused by other serogroups
have been reported, including those due to serogroup X. The capsular
polysaccharides of serogroups A and X are both homopolymers of amino sugars
(alpha-D-ManNAc and alpha-D-GlcNAc) containing phosphodiester linkages at C-6 and
C-4, respectively. The similarity of the primary structures of the two
polysaccharides suggests that serogroup A vaccination may provide cross
protection against serogroup X disease. Molecular dynamics simulations of a
series of serogroup A and X oligosaccharides reveal that the MenA CPS behaves as
a flexible random coil which becomes less conformationally defined as the length
increases, whereas serogroup X forms a more stable regular helical structure. The
presence of the MenX helix is supported by NMR analysis; it has four residues per
turn and becomes more stable as the chain length increases. Licensed MenA
vaccines are largely O-acetylated at C-3: simulations show that these O-acetyl
groups are highly solvent exposed and their presence favors more extended
conformations compared to the more compact conformations of MenA without O
acetylation. These findings may have implications for the design of optimal
conjugate vaccines.
PMID- 29940398
TI - The cognitive demands of remembering a speaker's perspective and managing common
ground size modulate 8- and 10-year-olds' perspective-taking abilities.
AB - Using "theory of mind" to successfully accommodate differing perspectives during
communication requires much more than just acquiring basic theory of mind
understanding. Evidence suggests that children's ability to adopt a speaker's
perspective continues to develop throughout childhood to adolescence until
adulthood. The current study examined the cognitive factors that could account
for variations in children's abilities to use a speaker's perspective during
language comprehension and whether the same factors contribute to age-related
improvements. Our study incorporated into a commonly used communication task two
types of memory demands that are frequently present in our everyday communication
but have been overlooked in the previous literature: remembering a speaker's
perspective and the amount of common ground information. Findings from two
experiments demonstrated that both 8- and 10-year-olds committed more egocentric
errors when each of these memory demands was high. Our study also found some
supporting evidence for the age-related improvement in children's perspective
use, with 10-year-olds generally committing fewer egocentric errors compared with
8-year-olds. Interestingly, there was no clear evidence that the memory factors
that affected children's perspective use in our experiments were also the factors
that drove age-related improvement.
PMID- 29940399
TI - Representing the location of manipulable objects in shape-selective
occipitotemporal cortex: Beyond retinotopic reference frames?
AB - When interacting with objects, we have to represent their location relative to
our bodies. To facilitate bodily reactions, location may be encoded in the brain
not just with respect to the retina (retinotopic reference frame), but also in
relation to the head, trunk or arm (collectively spatiotopic reference frames).
While spatiotopic reference frames for location encoding can be found in brain
areas for action planning, such as parietal areas, there is debate about the
existence of spatiotopic reference frames in higher-level occipitotemporal visual
areas. In an extensive multi-voxel pattern analysis (MVPA) fMRI study using
faces, headless bodies and scenes stimuli, Golomb and Kanwisher (2012) did not
find evidence for spatiotopic reference frames in shape-selective
occipitotemporal cortex. This finding is important for theories of how stimulus
location is encoded in the brain. It is possible, however, that their failure to
find spatiotopic reference frames is related to their stimuli: we typically do
not manipulate faces, headless bodies or scenes. It is plausible that we only
represent body-centred location when viewing objects that are typically
manipulated. Here, we tested for object location encoding in shape-selective
occipitotemporal cortex using manipulable object stimuli (balls and cups) in a
MVPA fMRI study. We employed Bayesian analyses to determine sample size and
evaluate the sensitivity of our data to test the hypothesis that location can be
encoded in a spatiotopic reference frame in shape-selective occipitotemporal
cortex over the null hypothesis of no spatiotopic location encoding. We found
strong evidence for retinotopic location encoding consistent with previous
findings that retinotopic reference frames are common neural representations of
object location. In contrast, when testing for spatiotopic encoding, we found
evidence that object location information for small manipulable objects is not
decodable in relation to the body in shape-selective occipitotemporal cortex.
Post-hoc exploratory analyses suggested that spatiotopic aspects might modulate
retinotopic location encoding. Overall, our findings provide evidence that there
is no spatiotopic encoding that is independent of retinotopic location in shape
selective occipitotemporal cortex.
PMID- 29940400
TI - Variations within a subtype: Developmental surface dyslexias in English.
AB - Surface dyslexia is characterised by poor reading of irregular words while
nonword reading can be completely normal. Previous work has identified several
theoretical possibilities for the underlying locus of impairment in surface
dyslexia. In this study, we systematically investigated whether children with
surface dyslexia showed different patterns of reading performance that could be
traced back to different underlying levels of impairment. To do this, we tested
12 English readers, replicating previous work in Hebrew (Gvion & Friedmann, 2013;
2016; Friedmann & Lukov, 2008; Friedmann & Gvion, 2016). In our sample, we found
that poor irregular word reading was associated with deficits at the level of the
orthographic input lexicon and with impaired access to meaning and spoken word
forms after processing written words in the orthographic input lexicon. There
were also children whose surface dyslexia seemed to be caused by impairments of
the phonological output lexicon. We suggest that further evidence is required to
unequivocally support a fourth pattern where the link between orthography and
meaning is intact while the link between orthography and spoken word forms is not
functioning. All patterns found were consistent with dual route theory while
possible patterns of results, which would be inconsistent with dual route theory,
were not detected.
PMID- 29940402
TI - Importance of breed aptitude (beef or dairy) in determining trace element
concentrations in bovine muscles.
AB - The aim of this study was to determine the concentrations of various trace
elements in muscles with different oxidative/glycolytic profiles (cardiac [CA];
diaphragm [DI], as oxidative; trapezius [TR], as intermediate
oxidative/glycolytic; and semimembranosus [SM], as glycolytic muscle) of ten
dairy-aptitude (Holstein-Friesian, HF), ten beef-aptitude (Galician Blonde, GB)
and ten cross-breed (GBxHF) calves. The type of muscle was a highly significant
factor in relation to the concentrations of all elements, whereas breed was only
significant for Fe, Mn and Zn in the SM muscle. The concentrations of the main
trace elements (Cu, Fe, Se and Zn) were significantly lower in GB and GBxHF than
in HF, that were mainly associated with differences in the oxidative/glycolytic
profile, probably due to the muscular hypertrophy characteristic of heavily
muscled breeds. The pattern of distribution was similar in all breeds, with
significantly higher concentrations in the CA muscle, followed by the DI; trace
element concentrations in the SM and TR muscles were very similar.
PMID- 29940401
TI - Do guided internet-based interventions result in clinically relevant changes for
patients with depression? An individual participant data meta-analysis.
AB - Little is known about clinically relevant changes in guided Internet-based
interventions for depression. Moreover, methodological and power limitations
preclude the identification of patients' groups that may benefit more from these
interventions. This study aimed to investigate response rates, remission rates,
and their moderators in randomized controlled trials (RCTs) comparing the effect
of guided Internet-based interventions for adult depression to control groups
using an individual patient data meta-analysis approach. Literature searches in
PubMed, Embase, PsycINFO and Cochrane Library resulted in 13,384 abstracts from
database inception to January 1, 2016. Twenty-four RCTs (4889 participants)
comparing a guided Internet-based intervention with a control group contributed
data to the analysis. Missing data were multiply imputed. To examine treatment
outcome on response and remission, mixed-effects models with participants nested
within studies were used. Response and remission rates were calculated using the
Reliable Change Index. The intervention group obtained significantly higher
response rates (OR = 2.49, 95% CI 2.17-2.85) and remission rates compared to
controls (OR = 2.41, 95% CI 2.07-2.79). The moderator analysis indicated that
older participants (OR = 1.01) and native-born participants (1.66) were more
likely to respond to treatment compared to younger participants and ethnic
minorities respectively. Age (OR = 1.01) and ethnicity (1.73) also moderated the
effects of treatment on remission.Moreover, adults with more severe depressive
symptoms at baseline were more likely to remit after receiving internet-based
treatment (OR = 1.19). Guided Internet-based interventions lead to substantial
positive treatment effects on treatment response and remission at post-treatment.
Thus, such interventions may complement existing services for depression and
potentially reduce the gap between the need and provision of evidence-based
treatments.
PMID- 29940403
TI - Effects of chitosan as a surface fungus inhibitor on microbiological,
physicochemical, oxidative and sensory characteristics of dry fermented sausages.
AB - The study aimed to improve the quality characteristics of Turkish dry-fermented
sausages (sucuk) using different concentrations of chitosan (CH) coating as
superficial mold inhibitor. The sausages were treated (w/w) with chitosan (0.2%,
CH1; 0.5%, CH2 and 1%, CH3), potassium sorbate (20%, PS), acetic acid (1%, AA)
and distilled water. Treatment with PS and CH3 resulted in a remarkable reduction
of mold and yeast counts in the sausages and on casings at the end of ripening.
Total aerobic mesophilic bacteria and lactic acid bacteria (LAB) varied from 7.19
7.29 to 9.01-9.27 and from 6.37-6.44 to 8.53-8.93 log CFU/g at day 0 and 12,
respectively. Treatment with chitosan did not affect the natural microbiota of
the sausages. Enterobacteriaceae counts were lowered from 5.79-5.89 to 2.08-2.53
log CFU/g by chitosan. Moreover, the rate of lipid oxidation in the sausages
decreased by chitosan treatment. Sensory attributes were also notably enhanced in
the cooked sausages treated with chitosan.
PMID- 29940404
TI - Predicting post-mortem meat quality in porcine longissimus lumborum using Raman,
near infrared and fluorescence spectroscopy.
AB - Spectroscopic techniques can provide valuable information about post-mortem meat
quality. In the current study, Raman, NIR and fluorescence spectroscopy was used
to analyze pH, drip loss and intramuscular fat in pork longissimus lumborum (n =
122) at 4-5 days post-mortem. Results were promising for partial least squares
regression (PLSR) from Raman spectroscopy, giving coefficients of determination
from cross validation (rcv2) ranging from 0.49 to 0.73 for all attributes
examined. Important regions in the PLSR models from Raman spectroscopy were
attributed to changes in concentrations of post-mortem metabolites and
modifications of protein secondary structure. Near infrared and fluorescence
spectroscopy showed limited ability to analyze quality, with rcv2 ranging from
0.06 to 0.57 and 0.04 to 0.18, respectively. This study encourages further
research on the subject of Raman spectroscopy as a technique for meat quality
analysis.
PMID- 29940405
TI - Evaluation of disseminated intravascular coagulation scores in critically ill
pediatric patients with septic shock.
AB - PURPOSE: To evaluated the outcome predictability of DIC scores in critically ill
children with septic shock. MATERIALS AND METHODS: Pediatric patients with septic
shock who were admitted to the pediatric intensive care unit of a tertiary care
children's hospital between January 2013 and December 2017 were enrolled. We
analyzed the association between DIC and clinical outcomes. DIC was diagnosed
based on the International Society on Thrombosis and Hemostasis (ISTH), Japanese
Association for Acute Medicine (JAAM), and modified JAAM DIC criteria. RESULTS:
Among the 89 patients, DIC was diagnosed in 66.3%, 61.8%, and 41.6% of patients
using the JAAM, modified JAAM, and ISTH DIC criteria, respectively. Overall 28
day mortality was 14.6%. DIC patients had worse outcomes, including a higher 28
day mortality and multiorgan dysfunction syndrome (MODS) than those without DIC.
The DIC scores were well correlated with the MODS scores. The JAAM and modified
JAAM DIC scores showed good outcome predictability (p < 0.05) with areas under
the receiver operating characteristic curve of 0.765 and 0.741, respectively.
CONCLUSIONS: Critically ill children with septic shock frequently experience DIC.
Patients with DIC had worse outcomes than those without DIC. JAAM and modified
JAAM DIC scores could be promising outcome predictors in these patients.
PMID- 29940406
TI - Predictive value of serum albumin levels on noradrenaline and fluid requirements
in the first 24 h after admission to the Intensive Care Unit - A prospective
observational study.
PMID- 29940407
TI - The immunobiology of ubiquitin-dependent B cell receptor functions.
AB - MHC class II-restricted antigen presentation by dendritic cells is necessary for
activation of naive CD4 T cells, whereas class II-restricted antigen presentation
by B lymphocytes and macrophages is important for the recruitment of CD4+ helper
and regulatory T cells. Antigen presentation by B cells is also important for
induction of T cell tolerance. B cells are unique among these three types of MHC
class II-expressing antigen presenting cells (APC) as they constitutively express
high levels of cell surface class II molecules and express a clonally restricted
antigen specific receptor, the B cell receptor (BCR). Here, I review our current
understanding of three major steps that underlie the processing and presentation
of BCR-bound cognate antigen: (1) endocytosis of antigen-BCR (Ag-BCR) complexes,
(2) Ag-BCR trafficking to intracellular antigen processing compartments and (3)
generation of antigenic peptide-MHC class II complexes, with a particular focus
on the role of BCR ubiquitination in each. I will highlight potential topics for
future research and briefly discuss the impact of the cell biology of BCR
mediated antigen processing on the response of the B cell and T cell to the cell
cell interactions mediated by B cell-expressed peptide-class II complexes.
PMID- 29940408
TI - Role of MAIT cells in pulmonary bacterial infection.
AB - Mucosal-associated invariant T (MAIT) cells represent a population of innate T
cells that is highly abundant in humans. MAIT cells recognize metabolites of the
microbial vitamin B pathway that are presented by the major histocompatibility
complex (MHC) class I-related protein MR1. Upon bacterial infection, activated
MAIT cells produce diverse cytokines and cytotoxic effector molecules and
accumulate at the site of infection, thus, MAIT cells have been shown to be
protective against various bacterial infections. Here, we summarize the current
knowledge of the role of MAIT cells in bacterial pulmonary infection models.
PMID- 29940409
TI - Immunoglobulin and T cell receptor genes in Chinese crocodile lizard Shinisaurus
crocodilurus.
AB - Squamata are reptiles that diverged from mammals 300 million years ago. During
this period, the immunoglobulin (IG) and T lymphocyte receptor (TCR) genes
evolved parallel to mammals. However, unlike mammals whose IG/TCR locus has
retained a constant structure throughout evolution, Squamata have witnessed
duplications, losses, and/or gains in the domains of their immunoglobulin genes.
The recent genome sequencing of Shinisaurus crocodilurus, a representative
species of the oldest reptiles, provides an opportunity to contrast the structure
of IG and TCR genes from previously studied Squamata. This study revealed ten
immunoglobulin genes: five genes for immunoglobulin M (IgM), two for
immunoglobulin D (IgD), one for immunoglobulin D2 (IgD2), and two for
immunoglobulin Y (IgY). As in other Squamata, there are genes for the lambda
light chain (IGLV) but not for the kappa chain (IGKV). Here, the data shows that
in some IgM genes, the cysteine needed to bind the lambda chains does not exist,
but we present evidence for possible non-covalent binding to the light chain.
With respect to TCR, one gene is detected for the alpha constant chain (TRAC) and
two genes for the beta constant chain (TRBC); one of which is located in the
locus of the variable regions of the heavy chain. As in the rest of the Squamata,
genes for the gamma/delta T cell receptor were not found. The V gene repertoire
is found to be consistent with all other Squamata with few V genes for beta chain
of TCR.
PMID- 29940410
TI - Narrow provider networks and willingness to pay for continuity of care and
network breadth.
AB - Tiered and narrow provider networks are mechanisms implemented by health plans to
reduce health care costs. The benefits of narrow networks for consumers usually
come in the form of lower premiums in exchange for access to fewer providers.
Narrow networks may disrupt continuity of care and access to usual sources of
care. We examine choices of health plans in a private health insurance exchange
where consumers choose among one broad network and four narrow network plans.
Using a discrete choice model with repeated choices, we estimate the willingness
to pay for a health plan that covers consumers' usual sources of care.
Willingness to pay for a network that covers consumers' usual source of care is
between $84 and $275/month (for primary care) and between $0 and $115/month (for
specialists). We find that, given that a network covers their usual source of
care, consumers show aversion only to the narrowest networks.
PMID- 29940411
TI - Implementation of triple the time spent on physical education in pre-school to
6th grade: A qualitative study from the programme managers' perspective.
AB - Schools constitute an important arena for promoting physical activity. However,
school-based programmes often face implementation challenges, and the
identification of factors influencing the implementation process is considered
important in order to secure the effectiveness of future interventions. The aim
of this study was to identify factors influencing the various implementation
stages during the initial years of a programme tripling the amount of physical
education at the primary school level. Document analysis of publicly available
programme descriptions and meeting minutes, were conducted. Document analysis was
complemented by two semi-structured group interviews with main programme managers
to gather in-depth programme experiences and perspectives. Results show that
early involvement of schools may ensure the best possible match between
programmes and the needs and resources of schools, and that an ongoing shared
partnership may help programme managers address program challenges in early
stages. It seems that predetermined core elements in programmes are essential. At
the same time programmes must be flexible enough for adaptation to individual
school contexts. Finally, the implementation of triple the amount of physical
education, is supported by teachers receiving a professional development course
focusing on how to organise outdoor physical education in different seasons and
weather conditions.
PMID- 29940412
TI - Spatiotemporal mapping of oxygen in a microbially-impacted packed bed using 19F
Nuclear magnetic resonance oximetry.
AB - 19F magnetic resonance has been used in the medical field for quantifying
oxygenation in blood, tissues, and tumors. The 19F NMR oximetry technique
exploits the affinity of molecular oxygen for liquid fluorocarbon phases, and the
resulting linear dependence of 19F spin-lattice relaxation rate R1 on local
oxygen concentration. Bacterial biofilms, aggregates of bacteria encased in a
self-secreted matrix of extracellular polymers, are important in environmental,
industrial, and clinical settings and oxygen gradients represent a critical
determinant of biofilm function. However, measurement of oxygen distribution in
biofilms and biofouled porous media is difficult. Here the ability of 19F NMR
oximetry to accurately track oxygen profile development in microbial impacted
packed bed systems without impacting oxygen transport is demonstrated. Time
stable and inert fluorocarbon containing particles are designed which act as
oxygen reporters in porous media systems. Particles are generated by emulsifying
and entrapping perfluorooctylbromide (PFOB) into alginate gel, resulting in
oxygen-sensing alginate beads that are then used as the solid matrix of the
packed bed. 19F oxygenation maps, when combined with 1H velocity maps, allow for
insight into the interplay between fluid dynamics and oxygen transport phenomena
in these complex biofouled systems. Spatial maps of oxygen consumption rate
constants are calculated. The growth characteristics of two bacteria, a non
biofilm forming Escherichia coli and Staphylococcus epidermidis, a strong biofilm
former, are used to demonstrate the novel data provided by the method.
PMID- 29940413
TI - The Prognostic Value of Tumor-Infiltrating lymphocytes in Stage II Colon Cancer.
A Nationwide Population-Based Study.
AB - BACKGROUND: Additional prognostic markers are needed for better treatment
stratification of stage II colon cancer (CC). We investigated the prognostic
value of tumor-infiltrating lymphocytes (TILs) in a true population-based cohort
of patients with stage II CC. MATERIAL AND METHODS: A total of 573 patients were
included. Tumor blocks representing the deepest invasive part of the primary
tumor were used for analysis. CD3+ and CD8+ TILs at the invasive front were
evaluated by immunohistochemistry on whole tumor sections. The invasive area was
manually outlined, and Visiopharm Integrator System software was used for
quantification. Data were dichotomized for comparison with clinical data. The
prognostic value was investigated in Cox proportional-hazard models for
recurrence-free survival (RFS) and overall survival (OS). RESULTS: Low CD3+ or
CD8+ TILs were significantly associated with poor RFS and OS (P = .0021 and P <=
.0009, respectively, log-rank test). In multiple Cox regression analysis, low
CD3+ and CD8+ TILs were associated with reduced RFS with hazard ratio (HR) =
1.386 (95% CI 1.039-1.850), P = .026, and HR = 1.394 (95% CI 1.029-1.890), P =
.032, respectively, independent of age, T-stage, localization, perforation, and
microsatellite instability (MSI). In the subgroups of patients with low CD3+ or
CD8+ TILs, there was no difference in survival between patients with MSI and
microsatellite-stable tumors, (P = .821 and P = .907, respectively). CONCLUSION:
Low CD3+ and CD8+ TILs in the invasive area are both related to inferior
prognosis of stage II CC, and we recommend either of these parameters to be
considered as additional high-risk factor.
PMID- 29940414
TI - Activating Transcription Factor 3 as a Novel Regulator of Chemotherapy Response
in Breast Cancer.
AB - Anthracyclines, such as doxorubicin, are used as first-line chemotherapeutics,
usually in combination therapies, for the treatment of advanced breast cancer.
While these drugs have been successful therapeutic options, their use is limited
due to serious drug related toxicities and acquired tumor resistance. Uncovering
the molecular mechanisms that mediate doxorubicin's cytotoxic effect will lead to
the identification of novel more efficacious combination therapies and allow for
reduced doses of doxorubicin to be administered while maintaining efficacy. In
our study, we demonstrate that activating transcription factor (ATF) 3 expression
was upregulated by doxorubicin treatment in a representative panel of human
breast cancer cell lines MCF7 and MDA-MB-231. We have also shown that doxorubicin
treatment can induce ATF3 expression in ex vivo human breast and ovarian tumor
samples. The upregulation of ATF3 in the cell lines was regulated by multiple
cellular mechanisms including the activation of JNK and ATM signaling pathways.
Importantly, loss of ATF3 expression resulted in reduced sensitivity to
doxorubicin treatment in mouse embryonic fibroblasts. Through a 1200 FDA-approved
compound library screen, we identified a number of agents whose cytotoxicity is
dependent on ATF3 expression that also enhanced doxorubicin induced cytotoxicity.
For example, the combination of the HDAC inhibitor vorinostat or the nucleoside
analogue trifluridine could synergistically enhance doxorubicin cytotoxicity in
the MCF7 cell line. Synergy in cell lines with the combination of ATF3 inducers
and patients with elevated basal levels of ATF3 shows enhanced response to
chemotherapy. Taken together, our results demonstrate a role for ATF3 in
mediating doxorubicin cytotoxicity and provide rationale for the combination of
ATF3-inducing agents with doxorubicin as a novel therapeutic approach.
PMID- 29940416
TI - Extrauterine adenomyoma: a review of the literature.
AB - Adenomyosis is the presence of endometrial glands and stroma within the
myometrium. The focal and localized form of adenomyosis is known as adenomyoma.
It is rarely located outside the uterus which is termed as extrauterine
adenomyoma. We describe three cases of extrauterine adenomyomas which were
located in pararectal space, round ligament and ovary. These cases were treated
by laparoscopic excision and diagnosis was confirmed by histopathological
examination. A review of the literature identified 34 cases of extrauterine
adenomyomas. The most common locations were pararectal space, ovary and broad
ligament. Other pelvic locations included the round ligament, paraovarian,
parametrial and pelvic wall. Extrapelvic adenomyomas were located in the liver,
upper abdomen, inguinal scar, appendix and small bowel mesentery. The
abdominopelvic pain was the most common clinical presentation of extrauterine
adenomyoma. Various imaging modalities were used to identify extrauterine masses,
but a definitive diagnosis could not be made preoperatively in any of the cases.
Although rare, a possible diagnosis of adenomyoma must be contemplated while
dealing with extrauterine masses. Surgical excision is the mainstay of treatment.
Since malignancy has been reported in extrauterine adenomyomas, this possibility
must be kept in mind while offering treatment.
PMID- 29940415
TI - The structural basis for filovirus neutralization by monoclonal antibodies.
AB - Filoviruses, including ebolaviruses and marburgviruses, are the causative agents
of highly lethal disease outbreaks. The 2013-2016 Ebola virus outbreak was
responsible for >28000 infections and >11000 deaths. Although there are currently
no licensed vaccines or therapeutics for any filovirus-induced disease,
monoclonal antibodies (mAbs) are among the most promising options for therapeutic
development. Hundreds of mAbs have been isolated from human survivors of
filovirus infections that target the viral spike glycoprotein (GP). The binding,
neutralization, and cross-reactivity of many of these mAbs has been determined.
Several mAbs have been characterized structurally, and this information has been
crucial for strategizing therapeutic and vaccine design. Here we present an
overview of the structural features of the neutralizing/protective epitopes on
filovirus glycoproteins.
PMID- 29940417
TI - Development and internal validation of a clinical prediction model for external
cephalic version.
AB - OBJECTIVE: To develop a prediction model for the chance of successful external
cephalic version (ECV). STUDY DESIGN: This is a secondary analysis of a
multicenter, open-label randomized controlled trial that assessed the
effectiveness of atosiban compared to fenoterol as uterine relaxant during ECV in
women with a singleton fetus in breech presentation with a gestational age of 36
weeks or more. Potential predictors included maternal, pregnancy, fetal, and
treatment characteristics and were recorded in all participants. Multivariable
logistic regression analysis with a stepwise backward selection procedure was
used to construct a prediction model for the occurrence of successful ECV. Model
performance was assessed using calibration and discrimination. RESULTS: We
included a total of 818 women with an overall ECV success rate of 37%. Ten
predictive factors were identified with the stepwise selection procedure to be
associated with a successful ECV: fenoterol as uterine relaxant, nulliparity,
Caucasian ethnicity, gestational age at ECV, Amniotic Fluid Index, type of breech
presentation, placental location, breech engagement, possibility to palpate the
head and relaxation of the uterus. Our model showed good calibration and a good
discriminative ability with a c-statistic of 0.78 (95% CI 0.75 to 0.81).
CONCLUSION: Prediction of success of ECV seems feasible with a model showing good
performance. This can be used in clinical practice after external validation.
PMID- 29940418
TI - Anxiety and depression in women with breast cancer: Social and clinical
determinants and influence of the social network and social support (DAMA
cohort).
AB - BACKGROUND: Anxiety and depression are the most prevalent mental health
pathologies among women with breast cancer. Social, clinical and contextual
variables may influence emotional stress among women with breast cancer. The aim
of this work is to study anxiety and depression in a cohort of women diagnosed
with breast cancer between 2003 and 2013 in Barcelona. We evaluate social and
clinical determinants. METHODS: We performed a mixed cohort study (prospective
and retrospective) using a convenience sample of women diagnosed with breast
cancer. The information sources were the Hospital Anxiety and Depression
questionnaire and hospital medical records. Dependent variables were anxiety and
depression; independent variables were social class, age, employment status,
tumour stage at diagnosis, time since diagnosis, social network and social
support. We performed a descriptive analysis, a bivariate analysis, and a
multivariate logistic regression analysis. RESULTS: A total of 1086 (48.6%) women
had some degree of anxiety-related problem. As for depression. In the case of
depression, 225 (15%) women had some degree of depression-related problem. Low
emotional support and social isolation were clear risk factors for having more
anxiety and depression. Low social class was also a risk factor, and age also
played a role. DISCUSSION: Our results show that women long period of cancer
survival have high prevalences of anxiety than depression, and this prevalence of
anxiety is higher than the general population. In addition, we found inequalities
between social classes and the isolation and social support are worse too in low
social class.
PMID- 29940419
TI - Effect of heat treatment on the luminescence properties of natural apatite.
AB - Regarding gemstone identification, the effect of heat treatment under reduction
condition to optical and luminescence properties of natural green apatite
(Ca5(PO4)3OH, F, Cl) from Madagascar has been investigated. Although electron
microprobe analysis (EPMA) shows a luminescence defect of rare earth element such
as Ce (0.47%), Pr (0.22%) and Nd (0.15%), however original sample does not show
luminescence properties. With consecutive heating process, the color alteration
from green to colorless of samples, and also the enhancement of luminescence
properties of Ce3+ in natural apatite was observed. Mechanism of fluorescence
enhancement and color changes during heating process were discussed using optical
spectra and emission spectra. Optical spectra of heated apatite point out that
green and blue color assigned to the existence of a photochromic center of Ce3+
SiO3- radical and SO3-, respectively. Consequently, the vanishing of these both
bands resulted in the colorless heated apatite at 800 degrees C. Heated apatite
showed emission band at 365 nm because of the deactivation of electron from 4f of
Ce3+ to 5d. Optical spectra reveal that the correlation of luminescence
enhancement and the fading of yellow tint of heated apatite by means of the
descending of Ce3+ to Ce4+ charge transfer process. The ultimate contribution of
this work is the finding of the difference of luminescence properties between non
heated and heated apatite which can be used as an effective tool for gem
identification. This identification tool is remarkable because it is rapid and
non-destructive.
PMID- 29940420
TI - Simultaneous peritoneal and retroperitoneal splenosis mimics metastatic right
adrenal mass.
AB - INTRODUCTION: Right retroperitoneal splenosis is rare with few reported cases. We
report, here, the case of simultaneous peritoneal and retroperitoneal splenosis
mimics metastatic right adrenal mass. PRESENTATION OF CASE: A 28-year-old man who
had previously undergone post traumatic splenectomy at childhood and subsequently
presented with an large incidental non-functioning right adrenal mass with
presence of extra-hepatic peritoneal focal lesion diagnosed as metastasis by
magnetic resonance imaging (MRI). Adrenalectomy with metatstectomy was performed,
and both masses were identified to be splenosis. DISCUSSION: Adrenal
incidentalomas (AIs) is defined as asymptomatic masses >1 cm. on cross-sectional
imaging studies. AIs have significant malignant potential for masses > 6 cm.
Splenosis are found most frequently in the left retroperitoneum in cases
involving retroperitoneal splenosis. However, right retroperitoneal splenosis
have been reported. Traditional imaging techniques cannot differentiate splenosis
from malignancy. CONCLUSION: Large right adrenal incidentalomas present with
other abdominal, peritoneal masses could be splenosis in patient following post
traumatic splenectomy.
PMID- 29940421
TI - Novel score predicts risk for cytomegalovirus infection in ulcerative colitis.
AB - BACKGROUND: Cytomegalovirus (CMV) infection is associated with relapse and
exacerbation of ulcerative colitis (UC), especially in immunosuppressed patients.
OBJECTIVES: The aim of this study was to identify risk factors for CMV colitis
and to develop a predictive risk score to estimate the probability of CMV colitis
in UC patients supporting clinical decision making. STUDY DESIGN: A cohort of 239
UC-patients was retrospectively analyzed. Univariate and multivariate regression
analysis identified several independent risk factors for CMV colitis and a
predictive risk score was established using ROC analysis. RESULTS: CMV colitis is
common in patients with severe ulcerative colitis. Clinical UC activity, disease
duration and extent as well as the use of steroids and anti-TNF-alpha agents were
identified as risk factors (p < 0.05 each). Based on five predictive parameters,
a web-based risk score was developed. A strong correlation between the predicted
and actual rates of CMV colitis was found (AUC: 0.855; 95% CI 0.79-0.92; p <
0.0001). CONCLUSIONS: Our study supports the pathogenic relevance of CMV in UC.
The predictive risk score estimates the risk of CMV colitis and might aid in
clinical decision making, especially when timely modifications of therapeutic
regimens are needed and reliable diagnostic tools are not readily available.
PMID- 29940422
TI - Evaluation of in vitro screening and diagnostic kits for hepatitis C virus
infection.
AB - BACKGROUND: To detect infection by hepatitis C virus (HCV), a reliable kit with
high sensitivity and specificity is indispensable. Detection kits for anti-HCV
antibodies (anti-HCV) are used for screening, and quantification kits for HCV RNA
and core antigen are used for definite diagnosis of HCV infection. OBJECTIVES: We
evaluated the performance of these kits using International Standards and a
regional reference panel with HCV negative and positive specimens. STUDY DESIGN:
In vitro diagnostic kits (10 anti-HCV, two HCV RNA, and three HCV core antigen)
were included. RESULTS: Nearly all specimens in the regional reference panel were
correctly identified by all anti-HCV detection kits (one false-positive was
observed in one kit). Both HCV RNA quantification kits also correctly identified
and quantified HCV RNA titers, without genotype-specific differences. Among the
HCV core antigen kits, International Standard values were inconsistent. The
sensitivities of these kits were insufficient to detect HCV in positive specimens
in the regional reference panel. CONCLUSIONS: In vitro diagnostic kits assessing
anti-HCV and HCV RNA have sufficient sensitivities and specificities to screen
and detect HCV infection. However, HCV core antigen quantification kits have some
limitations in their sensitivities and consistencies for diagnosis of HCV
infection. Quality control with International Standards and a regional reference
panel is important to maintain the performances of diagnostic kits for HCV
infection and to verify the clinical reliability of these kits.
PMID- 29940423
TI - The effect of age on outcomes after isolated limb perfusion for advanced
extremity malignancies.
AB - BACKGROUND: Isolated limb perfusion (ILP) is a well-established treatment for
patients with advanced extremity malignancies unsuitable for limb-conserving
surgery. However, little is known about the outcomes of this treatment in elderly
patients. We sought to determine the effects of age on the tolerability and
efficacy of ILP for advanced extremity malignancy. PATIENTS AND METHODS: Patients
undergoing ILP at our institution between January 2005 and January 2018 were
identified from a prospectively maintained database. Patients were stratified by
pathology (melanoma, soft-tissue sarcoma, other) and age (<75 years and >=75
years). Outcomes of interest were perioperative morbidity and mortality,
locoregional toxicities, response rates and oncological outcomes. RESULTS: During
the study period, a total of 189 perfusions were attempted. Successful perfusions
were performed in 179 patients, giving a technical success rate of 94.7%. No
difference in perfusion success rates, severe locoregional toxicity and
perioperative morbidity or mortality was noted between those aged <75 years and
>=75 years. The overall response rate in melanoma was 82.4%, and no difference in
response rates or oncological outcomes between age groups was noted in these
patients. The overall response rate in soft-tissue sarcoma was 63.5%, with no
difference in response rates noted between age groups. However, patients aged <75
years with soft-tissue sarcoma had prolonged local recurrence-free survival
compared with older patients (13 versus 6 months), possibly due to the prevalence
of chemosensitive subtypes in the younger age group. CONCLUSION: ILP is an
effective treatment for advanced extremity malignancies in the elderly, with
comparable response rates and toxicities to younger patients.
PMID- 29940425
TI - Sex differences in the effects of acute stress on behavior in the ultimatum game.
AB - Acute stress affects human decision making. It has been argued that there are
systematic sex differences in behavioral responses to acute stress, with males
showing a 'fight or flight' and females showing a 'tend and befriend' response. A
'tend and befriend' response would suggest that women become more cooperative
under acute stress, while men do not. We investigated the effects of acute stress
on social behavior. We induced stress via the Trier Social Stress Test (TSST) and
then immediately after measured how participants reacted to offers made in the
ultimatum game by a male proposer. We found that female participants were less
likely to reject offers under stress (n = 25) vs. no stress (n = 37), p = 0.009,
independent of how fair these offers were, cooperative behavior consistent with
the 'tend and befriend' hypothesis. Male participants when stressed (n = 30) did
not show differences in rejections rates compared to the control condition (n =
26), p = 0.41. Our results provide support for a qualitatively different
behavioral response to acute stress among men and women.
PMID- 29940426
TI - Maternal high fat diet alters offspring epigenetic regulators, amygdala
glutamatergic profile and anxiety.
AB - Maternal obesity during pregnancy can impact long-term health, predisposition to
disease, and risk of neurological disorders in offspring. This may arise from
disruption to epigenetic processes during offspring brain development. Using a
maternal high fat diet (mHFD) mouse model, we investigated the expression of
genes encoding epigenetic regulators in the brains of gestational day (GD) 17.5
mHFD offspring. We found significant, regionally unique changes in expression of
epigenetic regulators in the developing brain of mHFD offspring compared to
controls, with Gadd45b downregulated in medial prefrontal cortex, Mecp2
downregulated in amygdala, and sex-specific downregulation of Crebbp, Dnmt3b, and
Mecp2 in male mHFD hippocampus. Decreased Mecp2 in the amygdala was associated
with significant upregulation of the Mecp2-repressed gene, Tbr1, and an increased
number of TBR1+ glutamatergic neurons in the basomedial nucleus of the amygdala.
Tbr1 upregulation in amygdala was also observed in postnatal day 8 (P8) mHFD
offspring, and levels of glutamate receptor gene Grin2b, and Fos, a marker for
neuronal activity, were increased. Indications of heightened excitatory drive in
mHFD offspring amygdala were associated with an anxiety-like phenotype, with mHFD
offspring displaying altered ultrasonic vocalization characteristics at P8, and
adult female mHFD offspring spending decreased time on the open arm of the
Elevated Plus Maze. Together, this data provides insight into sex-specific
offspring vulnerability to perinatal mHFD programming of anxiety-like behaviors.
PMID- 29940424
TI - Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on
chromatinized DNA.
AB - 8-Oxoguanine DNA glycosylase 1 (OGG1) initiates the base excision repair pathway
by removing one of the most abundant DNA lesions, 8-oxo-7,8-dihydroguanine (8
oxoG). Recent data showed that 8-oxoG not only is a pro-mutagenic genomic base
lesion, but also functions as an epigenetic mark and that consequently OGG1
acquire distinct roles in modulation of gene expression. In support, lack of
functional OGG1 in Ogg1-/- mice led to an altered expression of genes including
those responsible for the aberrant innate and adaptive immune responses and
susceptibility to metabolic disorders. Therefore, the present study examined
stimulus-driven OGG1-DNA interactions at whole genome level using chromatin
immunoprecipitation (ChIP)-coupled sequencing, and the roles of OGG1 enriched on
the genome were validated by molecular and system-level approaches. Results
showed that signaling levels of cellular ROS generated by TNFalpha, induced
enrichment of OGG1 at specific sites of chromatinized DNA, primarily in the
regulatory regions of genes. OGG1-ChIP-ed genes are associated with important
cellular and biological processes and OGG1 enrichment was limited to a time scale
required for immediate cellular responses. Prevention of OGG1-DNA interactions by
siRNA depletion led to modulation of NF-kappaB's DNA occupancy and differential
expression of genes. Taken together these data show TNFalpha-ROS-driven
enrichment of OGG1 at gene regulatory regions in the chromatinized DNA, which is
a prerequisite to modulation of gene expression for prompt cellular responses to
oxidant stress.
PMID- 29940427
TI - Stress induced cortisol release and schizotypy - The importance of cognitive
slippage and neuroticism.
PMID- 29940428
TI - Oxytocin receptor mRNA expression in dorsolateral prefrontal cortex in major
psychiatric disorders: A human post-mortem study.
AB - There is growing interest in oxytocin as a putative treatment for various
psychiatric disorders including major depressive disorder, bipolar disorder and
schizophrenia/schizoaffective disorder. However, potential alterations in the
endogenous brain oxytocin system in these disorders are poorly characterized.
Brain expression of oxytocin and its receptor genes in patients with these
psychiatric disorders has not been well studied outside the hypothalamus. We
measured expression of mRNA for oxytocin and its receptor in the dorsolateral
prefrontal cortex of postmortem brains using quantitative polymerase chain
reaction in a total of 581 individuals. These individuals either were diagnosed
with major depressive disorder (n = 135), bipolar disorder (n = 57),
schizophrenia/schizoaffective disorder (n = 169), or were control subjects,
defined as individuals with no lifetime history of any of these disorders (n =
220). Diagnoses of major depressive disorder and bipolar disorder were associated
with significantly increased oxytocin receptor mRNA levels in the dorsolateral
prefrontal cortex. This finding is discussed in light of the extant literature on
the dysregulation of oxytocin signaling in individuals with major psychiatric
disorders.
PMID- 29940429
TI - Comparative psychology without consciousness.
AB - The goal of this paper is to establish the truth of the following conditional: if
a global workspace theory of phenomenal consciousness is correct, and is fully
reductive in nature, then we should stop asking questions about consciousness in
nonhuman animals-not because those questions are too hard to answer, but because
there are no substantive facts to discover. The argument in support of this
conditional turns on the idea that while global broadcasting is all-or-nothing in
the human mind, it is framed in terms that imply gradations across species. Yet
our concept of phenomenal consciousness doesn't permit mental states to be to
some degree conscious. Before getting to that argument, however, and in order to
motivate the subsequent discussion, some of the virtues of global workspace
theory are displayed.
PMID- 29940430
TI - Social enterprises and public health improvement in England: a qualitative case
study.
AB - OBJECTIVES: To explore the contribution of social enterprises to publicly
commissioned public health improvement and assess the risks and benefits of their
role. STUDY DESIGN: Qualitative case study of four south London boroughs.
METHODS: Documentary research; in-depth interviews with 19 key informants.
RESULTS: This study identified 24 social enterprises that were currently
commissioned to contribute to public health improvement. These organisations
ranged in size, longevity, and structure. They were widely reported as flexible
and able to rapidly develop services responsive to local community needs. Their
work often addressed upstream health determinants. However, to capitalise on
securing contracts, they had to bureaucratise and establish provider alliances,
which risked losing the very characteristics that make them unique. Social
enterprises bore the financial risk of innovative service developments. Emerging
mixed economies of public health were fragmented, limiting commissioners'
abilities to plan strategically and evaluate the impact. CONCLUSIONS: Social
enterprises have an increasing role in providing potential solutions to
intractable health improvement challenges, contributing to a broader vision
around upstream action for health. However, the fragmentation and growing
outsourcing of public health has risks for coherent and equitable service
planning.
PMID- 29940431
TI - Prenatal exposure to polybrominated diphenyl ethers and predisposition to
frustration at 7 months: Results from the MIREC study.
AB - BACKGROUND: Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been
associated with cognitive deficits and behavioral problems in children. To date,
no study has examined this exposure in association with neurobehavioral
development in infants younger than 12 months assessed with observational tasks.
OBJECTIVES: This study examined the relation between prenatal PBDE concentrations
and predisposition to frustration, assessed by the arm restraint task (ART), in
Canadian infants. METHODS: In a prospective longitudinal study conducted in
Canada, exposure to nine PBDE congeners was measured in maternal plasma during
the first trimester of pregnancy. The ART was used to measure predisposition to
frustration in infancy (N = 333; mean age = 6.9 months), as assessed by negative
vocalizations (crying and screaming) and physical reactivity (discomfort
movements). RESULTS: Maternal plasma PBDE-47 concentrations collected during
pregnancy were associated with negative vocalizations using the ART (adjusted
Relative Risk [aRR] = 1.04, 95% CI: 1.00, 1.09). Prenatal PBDE-99 concentrations
during pregnancy were also related to a shift to the left in the tail of the
distribution of onset of negative vocalizations as measured by a decrease of 38 s
(95% CI: -78.1, 1.3) in the 75th quantile of the distribution for infants whose
mothers had detectable levels of PBDE-99 compared to infants of mothers with
undetectable levels. Similarly, infants whose mothers had detectable levels of
PBDE-100 showed an increase of 24.1 s (95% CI: 4.1, 44.1) in the 75th quantile of
the distribution of proportion of time in negative vocalizations compared with
infants of mothers with undetectable levels. Finally, the association between
PBDE-47 and PBDE-153, and physical reactivity was significantly modified by sex
(p < 0.1), with opposite patterns in girls and boys. CONCLUSIONS: Prenatal
exposure to PBDEs was associated with increased incidence of crying and screaming
with delayed onset of discomfort movement, which may indicate a predisposition to
frustration and lack of habituation in infants younger than 12 months from the
general population.
PMID- 29940432
TI - Facilitating student performance conversations: A framework for success.
AB - Nurse educators are considered the gatekeepers of the profession. They teach
students the skills and values needed for their role and prepare them to be
competent, ethical beginner nurses. Evaluation of these growing skills begins in
the first term and continues through their four-year journey. An important skill
for nurse educators is facilitating performance conversations with students who
are not meeting curricula requirements. This can be challenging as many barriers
exist to impede this required feedback. A literature review revealed consistent
barriers to effective performance conversations and suggested methods/tools to
help overcome these barriers. A Performance Conversation Concept Map was
developed, based on findings in the literature, and is presented to illustrate
intrinsic and extrinsic barriers, supportive tools/methods, and potential
outcomes that may result from successful performance conversations. This
analytical paper evaluates what the literature revealed and describes how the
elements of the concept map can be used as a framework to support new educator
competency during performance conversations.
PMID- 29940433
TI - Emotional engagement, educational aspirations, and their association during
secondary school.
AB - Previous research has demonstrated the link between school engagement and
academic attainment, but there is less understanding of the relationship between
school engagement and educational aspirations. Using the Longitudinal Study of
Young People in England (LSYPE), this study examines the association between
emotional engagement and educational aspirations during secondary school,
covering ages 14 to 16. On average, emotional engagement increased over time. A
significant proportion of adolescents shifted from expressing uncertainty to
aspiring to continue in education. Males were more likely than females to shift
from aspiring to continue in education to planning to leave school early. Greater
emotional engagement was associated with a lower likelihood of having low or
uncertain aspirations, especially for high-achieving, ethnic minority, and male
adolescents. Findings highlight the importance of emotional engagement,
particularly for those at risk of uncertain educational aspirations and those
least likely to continue in education following post-compulsory schooling.
PMID- 29940434
TI - Sudden death in a female child doe to undiagnosed pleuropulmonary blastoma - An
autopsy case and review of literature.
PMID- 29940435
TI - Human odor and forensics: Towards Bayesian suspect identification using GC * GC
MS characterization of hand odor.
AB - A new method for identifying people by their odor is proposed. In this approach,
subjects are characterized by a GC * GC-MS chromatogram of a sample of their hand
odor. The method is based on the definition of a distance between odor
chromatograms and the application of Bayesian hypothesis testing. Using a
calibration panel of subjects for whom several odor chromatograms are available,
the densities of the distance between chromatograms of the same person, and
between chromatograms of different persons are estimated. Given the distance
between a reference and a query chromatogram, the Bayesian framework provides an
estimate of the probability that the corresponding two odor samples come from the
same person. We tested the method on a panel that is fully independent from the
calibration panel, with promising results for forensic applications.
PMID- 29940436
TI - Simultaneous quantification of antibiotics in wastewater from pig farms by
capillary electrophoresis.
AB - Pig farming is an important activity in the economic development of Mexico with
millions of tons of meat produced annually. Antibiotics are used in therapeutic
dose to prevent diseases, and sometimes as growth promoters. These compounds are
not completely metabolized; they are carried into the environment in its active
form at concentrations that could induce antibiotic resistance in bacteria, which
could be transferred to human pathogens by horizontal gene transfer. The
objective of this work was to develop methods of analysis for simultaneous
quantification of the antibiotics Oxytetracycline (OXT), Chlortetracycline (CLT),
Enrofloxacin (ENRO) and Ciprofloxacin (CIPRO) by field-amplified sampling
injection in capillary zone electrophoresis (FASI-CZE). The method was validated
by parameters of (1) linearity, obtaining a lineal range of 0.05 at 1 MUg mL-1
for ENRO and CIPRO, and from 0.1 to 1 MUg mL-1 for OXT and CLT; (2) precision,
obtaining values <5% of standard deviation for CIPRO and ENRO and <10% of
standard deviation for OXT and CLT; (3) accuracy, with recovery values from 93 to
115%; (4) selectivity, with values of resolution >2 for the all antibiotics
tested. To prove the method, a sample of wastewater from a local pig farm was
analyzed, detecting a concentration of 0.140 +/- 0.009 for OXT. This
concentration was higher than the minimal selective concentration, indicating the
point in which resistance to a determined antibiotic could develop. The methods
were validated with precision and sensitivity comparable to chromatographic
methods, which can be used to analyze wastewater from pig farms directly.
PMID- 29940437
TI - Evaluating the effects of metal oxide nanoparticles (TiO2, Al2O3, SiO2 and CeO2)
on anammox process: Performance, microflora and sludge properties.
AB - The increasing use of engineered metal oxide nanoparticles (MONPs) in consumer
products raises great concerns about their environmental impacts, but their
potential impacts on anaerobic ammonium oxidation (anammox) process in wastewater
treatment remain unclear. In this study, the presence of MONPs (1, 50, 200 mg L
1) exhibited no visible effects on the nitrogen removal performance of anammox
reactors, but high levels (200 mg L-1) of SiO2NPs, Al2O3NPs and CeO2NPs had a
distinct effect on shaping the anammox community. Long-term exposure of MONPs
caused different responses in the relative abundance of Ca. Kuenenia, the level
of functional gene HzsA and the activities of three key enzymes involved in
anammox metabolism, but no significant inhibition effects on specific anammox
activity were detected. Overall, the effects of MONPs on anammox community
structure and sludge properties depended on their types and levels and followed
the order SiO2 > CeO2 > Al2O3 > TiO2.
PMID- 29940438
TI - The cellulose binding region in Trichoderma reesei cellobiohydrolase I has a
higher capacity in improving crystalline cellulose degradation than that of
Penicillium oxalicum.
AB - Commercial cellulase preparations for lignocellulose bioconversion are mainly
produced by the fungus Trichoderma reesei. The maximum cellulose conversion of T.
reesei cellulase mixture was 15%-20% higher than that of Penicillium oxalicum in
the hydrolysis of corncob residue and Avicel. Nevertheless, both preparations
hydrolyzed more than 92% of cellulose in NaOH-mercerized Avicel. When added to
Avicel hydrolysis residue that was less reactive to P. oxalicum cellulases,
cellobiohydrolase I (CBH I) from T. reesei resulted in a higher cellulose
conversion than its homologous proteins from P. oxalicum and Aspergillus niger at
the same protein loadings. Further domain exchange experiment attributed the high
hydrolytic efficiency of T. reesei CBH I to its inter-domain linker and cellulose
binding domain. The results in part explained the superior performance of T.
reesei cellulases on the degradation of native crystalline cellulose, and
highlighted the important role of cellulose-binding region in determining the
degree of hydrolysis by cellulases.
PMID- 29940439
TI - Effectively converting carbon dioxide into succinic acid under mild pressure with
Actinobacillus succinogenes by an integrated fermentation and membrane separation
process.
AB - The aim of the present study is to develop an effective bioprocess for converting
CO2 into succinic acid (SA) with Actinobacillus succinogenes by an integrated
fermentation and membrane separation process. CO2 could be effectively converted
into SA using NaOH as the neutralizer under the completely closed exhaust pipe
case with self-circulation of CO2 in the bioreactor. Meanwhile, the optimal CO2
partial pressure was 0.4 bar. In addition, a 300 kDa ultrafiltration (UF)
membrane was preferred for constructing the membrane bioreactor. Moreover, a high
conductivity was toxic to the cells during SA biosynthesis. After removing the
high concentration salts by in-situ membrane filtration, the SA productivity and
CO2 fixation rate increased by 39.2% compared with the batch culture, reaching
1.39 g.L-1.h-1 and 0.52 g.L-1.h-1 respectively. Furthermore, nanofiltration (NF)
was suitable for purifying the SA and recovering the residual substrates in the
UF permeate for the next fermentation.
PMID- 29940440
TI - A conservation decision-making framework based on ecosystem service hotspot and
interaction analyses on multiple scales.
AB - Ecosystem service (ES) hotspot mapping is a promising method to spatially
identify priority areas for conservation planning. Our study aims to develop a
decision-making framework for ES conservation across administrative levels based
on ES hotspot and interaction analyses on multiple spatial scales. To demonstrate
the framework, we used the Dianchi Lake watershed and the Kunming Prefecture in
Southwestern China as examples. We quantified six ES: crop productivity, water
yield, habitat quality, soil conservation, total phosphorus retention, and
recreation potential. In addition, we produced hotspot maps of single and
multiple ES on the pixel, sub-river basin, and river basin scales and calculated
the correlation coefficients between the services on these three scales. The
decision-making framework was developed based on answering four questions: Who
should make conservation decisions? Where should conservation be implemented?
What should be conserved? How can ES be conserved? The results demonstrated that
the spatial patterns of hotspots of single ES and the interactions among services
were dependent on the scale in the Dianchi Lake watershed. In addition, the
hotspot overlaps between ES were very poor and the spatial pattern of hotspot
overlaps was dependent on what services were chosen. The framework developed in
this study can be used to determine the decision-makers, find high priority
conservation areas, identify the services that should be conserved, and find the
way in which the services can be conserved. The framework provides ES information
on multiple spatial scales and can thus facilitate the decision-making process at
different administrative levels. In addition, the framework fits into the top
down decision-making system and may help decision-makers generate policies
tailored to local realities; therefore, the framework has potential to be used by
regional and local administrative decision-makers.
PMID- 29940441
TI - Removal of antibiotic resistance genes in two tertiary level municipal wastewater
treatment plants.
AB - Raw wastewater can contain high levels of antibiotic resistance genes (ARGs),
making municipal wastewater treatment plants (WWTPs) critical for the control of
the release of ARGs into the environment. The objective of this study was to
investigate how individual treatment steps in two tertiary WWTPs affected the
removal (copies/mL) and relative abundance of ARGs (copies/copies 16S rRNA
genes). Nine ARG markers, representing resistance to commonly used antibiotics,
as well as one integron gene (intl1) to assess ARG mobility potential, were
quantified using quantitative real-time PCR (qPCR). Both WWTPs met provincial
effluent regulations for removal of carbonaceous oxygen demand (CBOD5) and total
suspended solids. Eight of the ten ARG markers (intl1, sul1, sul2, tet(O), ermB,
blaCTX-M, blaTEM, qnrS) were detected in all samples. In contrast, mecA was
detected intermittently and vanA remained below the detection limit in all
samples. The total ARG marker abundances decreased by log 1.77 (p < 0.05) in the
plant using an aerated lagoon (AL), and by 2.69 logs (p < 0.05) through treatment
in the plant employing a biological nutrient removal (BNR) system. The BNR and
secondary clarifier steps in both plants afforded the most removal of ARGs. The
relative abundance of ARGs remained unchanged at the AL plant and showed a
decreasing trend at the BNR plant. Levels of CBOD5, nitrate and the human
Bacteroides fecal marker correlated with ARG concentrations, suggesting these
variables may be useful in predicting ARG removal. In conclusion, the effluent
coming from the WWTPs contained eight of the studied ARG markers in
concentrations ranging from 0.01 to 3.6 log copies/mL, indicating their release
into the environment, however, the relative abundance of ARGs was not enriched
during treatment in the two WWTPs.
PMID- 29940442
TI - Effects of urbanization on direct runoff characteristics in urban functional
zones.
AB - As urbanization processes, the increasing direct runoff caused by land use change
has become a major challenge for urban hydrological system. In this study, the
impact of urbanization on direct runoff in the Shenyang urban area was
investigated using a modified Soil Conservation Service Curve Number model
combined with remote sensing. Urban functional zone (UFZ) was used as the basic
unit for hydrological analysis. The hydrological changes in runoff were analyzed
by calculating the runoff difference between the current condition and the pre
urbanization condition. Moran's I was used to estimate the spatial
autocorrelation of the entire area. Then we assessed the relative influence and
marginal effects of factors affecting direct runoff using boosted regression
trees (BRT). Our results showed that direct runoff was significantly related to
urbanization. Under current conditions, direct runoff increment depth affected by
urbanization in the study area was 68.02 mm. For different UFZs, high-density
residential, business and industrial zones tended to have large runoff volumes
and high runoff coefficients. Through flooding hazard analysis, we found about
6.53% of the study area fell into a significant hazard category. The industrial
zone had largest area of significant hazard land (40.97 km2) and the business
zone had the largest significant hazard percentage (21.19%). Moran's I results
illustrated that the high-high clusters in Shenyang were mainly concentrated in
the urban center. BRT analysis indicated that runoff had the strongest
correlation with rainfall (52.07%), followed by impervious ratio (27.28%),
normalized difference vegetation index (14.31%), antecedent 5-day rainfall
(3.02%), and UFZs (1.70%). The industrial zone, business zone and high-density
residential zone tend to have greater influence on runoff. Our study could
present method for recognizing hotspots of direct runoff in large city, and may
provide potential implications for green infrastructure selection and urban
planning.
PMID- 29940443
TI - Long-term succession of aquatic plants reconstructed from palynological records
in a shallow freshwater lake.
AB - Aquatic plants in shallow freshwater lakes play a key role in stabilizing
ecological function and providing valuable ecosystem services, yet they are
severely degraded worldwide. An improved understanding of long-term aquatic plant
succession is critical to investigate the potential driving mechanisms and to
facilitate ecological restoration. In this paper, we reconstructed changes in the
aquatic plant community over the past century based on palynological records from
Changdang Lake, Middle and Lower Yangtze River Basin (MLYB), China. Our results
reveal that aquatic plants in Changdang Lake have undergone three clear phases:
emergent macrophytes dominated the aquatic vegetation in the 1900s-1970s,
submerged macrophytes in the 1970s-1990s, and floating macrophytes increasingly
after the 1990s. Significant changes in the aquatic plant communities were caused
by increasing anthropogenic pressures, such as damming and nutrient loading from
agriculture, aquaculture, and urbanization after the Chinese economic reform. We
argue that Changdang Lake is currently in a transition phase between a macrophyte
dominated state and an algae-dominated state. Our palynological record is
different from many contemporary studies, which suggest submerged plants
dominated most lakes in this region before the 1950s. We suggest that the return
of the aquatic plants to their 1970s-1980s state would be a realistic target for
lake restoration. Our results show that palynological records can reveal long
term dynamics of macrophytes in shallow lakes for sustainable lake restoration
and management.
PMID- 29940444
TI - Maternal transfer of nanoplastics to offspring in zebrafish (Danio rerio): A case
study with nanopolystyrene.
AB - Plastics are ubiquitous anthropogenic contaminants that are a growing concern in
aquatic environments. The ecological implications of macroplastics pollution are
well documented, but less is known about nanoplastics. The current study
investigates the potential adverse effects of nanoplastics, which likely
contribute to the ecological burden of plastic pollution. To this end, we
examined whether a dietary exposure of adult zebrafish (Danio rerio) to
polystyrene nanoparticles (PS NPs) could lead to the transfer of nanoplastics to
the offspring, and whether nanoplastics exposure affects zebrafish physiology.
Specifically, adult female and male zebrafish (F0 generation) were exposed to PS
NPs via diet for one week and bred to produce the F1 generation. Four F1 groups
were generated: control (unexposed females and males), maternal (exposed
females), paternal (exposed males), and co-parental (exposed males and females).
Co-parental PS NP exposure did not significantly affect reproductive success.
Assessment of tissues from F0 fish revealed that exposure to PS NPs significantly
reduced glutathione reductase activity in brain, muscle, and testes, but did not
affect mitochondrial function parameters in heart or gonads. Assessment of F1
embryos and larvae revealed that PS NPs were present in the yolk sac,
gastrointestinal tract, liver, and pancreas of the maternally and co-parentally
exposed F1 embryos/larvae. Bradycardia was also observed in embryos from maternal
and co-parental exposure groups. In addition, the activity of glutathione
reductase and the levels of thiols were reduced in F1 embryos/larvae from
maternal and/or co-parental exposure groups. Mitochondrial function and locomotor
activity were not affected in F1 larvae. This study demonstrates that (i) PS NPs
are transferred from mothers to offspring, and (ii) exposure to PS NPs modifies
the antioxidant system in adult tissues and F1 larvae. We conclude that PS NPs
could bioaccumulate and be passed on to the offspring, but this does not lead to
major physiological disturbances.
PMID- 29940445
TI - Mapping soil organic matter in the Baranja region (Croatia): Geological and
anthropic forcing parameters.
AB - Spatial mapping of soil organic matter (SOM) and evaluation of the related
natural and anthropic influencing factors are crucial to monitor the extent of
degraded land and the evolution of soil functions. The objective of this work is
to study the spatial distribution of SOM in a highly exploited agricultural area
in the Baranja Region (Croatia). The spatially dense dataset available (4825 top
soil samples from 0 to 30 cm) allowed to produce reliable SOM maps using
geostatistical interpolation kriging algorithms and to study the relationships
with possible influencing factors. The interpolation has been conducted by means
of two approaches. In one approach, the overall data set is considered for
computing a global variogram and performing a direct interpolation of SOM values.
In the second approach, the data are stratified according to two different
geological and morphogenetic domains, Holocene Domain (HD) and Pleistocene Domain
(PD), and a distinct geostatistical analysis is performed in each domain. The
results showed that average SOM in the studied region was 2.29%, indicating a
future need for adopting sustainable soil management practices in this region.
SOM was significantly higher in HD (2.64%) than PD (1.97%) domain. SOM in PD
generally had a much lower global variability. Global dataset analysis reveals
that regional intrinsic factors prevail over local intrinsic and extrinsic
factors in determining SOM spatial patterns. In contrast, the stratified approach
can filter the effect of regional variability related to the main geological and
geomorphological setting. The structural spatial correlation in PD is weaker than
in HD, as manifested by spatial patches of low and high SOM content with smaller
extension in PD with respect to HD. The strong relationships between SOM spatial
patterns and geological/geomorphological factors suggest the possibility of
adopting finer subdivision criteria in future research.
PMID- 29940446
TI - Valuing scarce observation of rainfall variability with flexible semi-distributed
hydrological modelling - Mountainous Mediterranean context.
AB - To represent spatial and temporal variability in rainfall adequately, rainfall
runoff models must compromise among modelling objectives, data availability,
conceptualization options, and the actual variability in rainfall. This is of
utmost importance for challenges of integrated water management in the rapidly
changing Mediterranean context. We evaluated the sensitivity of the SWAT model to
combinations of spatial rainfall variability and catchment subdivision in a data
scarce mesoscale mountainous Mediterranean context. The case study focused on the
Joumine catchment, in northern Tunisia, which is emblematic of agro-hydro
chemical changes and challenges. The double-mass curve method was used to verify
the consistency of rainfall time series from 1991 to 2003, indicating
proportionality between annual rainfall at the reference gauge and that of the
nearest gauge. The rainfall lapse rate at the Joumine catchment was 69.9 mm per
100 m of altitude. Seven sets of rain gauges and five subdivision configurations
of the catchment were simulated. Differences between measured and predicted
streamflow at the outlet were assessed using three indices of model fit.
Predicted streamflow was extremely sensitive to spatial rainfall variability but
relatively insensitive to catchment subdivision. Daily predictions were most
accurate for the wettest year (2002-2003) and least accurate for the driest year
(1993-1994).
PMID- 29940447
TI - Effects of elevated CO2 and endophytic bacterium on photosynthetic
characteristics and cadmium accumulation in Sedum alfredii.
AB - Elevated CO2 and use of endophytic microorganisms have been considered as
efficient and novel ways to improve phytoextraction efficiency. However, the
interactive effects of elevated CO2 and endophytes on hyperaccumulator is poorly
understood. In this study, a hydroponics experiment was conducted to investigate
the combined effect of elevated CO2 (eCO2) and inoculation with endophyte SaMR12
(ES) on the photosynthetic characteristics and cadmium (Cd) accumulation in
hyperaccumulator Sedum alfredii. The results showed that eCO2 * ES interaction
promoted the growth of S. alfredii, shoot and root biomass net increment were
increased by 264.7 and 392.3%, respectively, as compared with plants grown in
ambient CO2 (aCO2). The interaction of eCO2 and ES significantly (P < 0.05)
increased chlorophyll content (53.2%), Pn (111.6%), Pnmax (59.8%), AQY (65.1%),
and Lsp (28.8%), but reduced Gs, Tr, Rd, and Lcp. Increased photosynthetic
efficiency was associated with higher activities of rubisco, Ca2+-ATPase, and
Mg2+-ATPase, and linked with over-expression of two photosystem related genes
(SaPsbS and SaLhcb2). PS II activities were significantly (P < 0.05) enhanced
with Fv/Fm and Phi(II) increased by 12.3 and 13.0%, respectively, compared with
plants grown in aCO2. In addition, the net uptake of Cd in the shoot and root
tissue of S. alfredii grown in eCO2 * ES treatment was increased by 260.7 and
434.9%, respectively, due to increased expression of SaHMA2 and SaCAX2 Cd
transporter genes. Our results suggest that eCO2 * ES can promote the growth of
S. alfredii due to increased photosynthetic efficiency, and improve Cd
accumulation and showed considerable potential of improving the phytoextraction
ability of Cd by S. alfredii.
PMID- 29940448
TI - Micro-irrigation improves grain yield and resource use efficiency by co-locating
the roots and N-fertilizer distribution of winter wheat in the North China Plain.
AB - Water use efficiency (WUE) and nitrogen fertilizer use efficiency (NUE) of winter
wheat are urgently needed to further improve in the North China Plain (NCP). In
this study, a 3-year field experiment was conducted during the 2014-2017 growing
seasons to clarify the effect of traditional flood irrigation (TI), surface drip
irrigation (DI), and micro-sprinkling irrigation (MSI) on grain yield, WUE, and
NUE of winter wheat. Across the 3 years, grain yield of DI and MSI improved by
9.79% and 14.1%, WUE of DI and MSI increased by 12.3% and 17.7%, and NUE of DI
and MSI increased by 9.77% and 14.0%, respectively compared with those of TI.
Wheat subjected to the micro-irrigation treatments (DI and MSI) had higher
chlorophyll content in flag leaves 10 days post-anthesis; this postponed
senescence of the flag leaves, which increased dry matter accumulation post
anthesis, and increased 1000-grain weight and grain yield. The micro-irrigation
treatments reduced pre-anthesis water consumption but increased post-anthesis
water consumption and ensured the water supply in the top soil layer at the
critical stage, thus increasing WUE. Root length density (RLD) of TI in the 0-80
cm soil layer was significantly higher than that of micro-irrigation, whereas
micro-irrigation had higher RLD than TI below the 80-cm soil layer, which
promoted the absorption and utilization of water and nitrogen in deep soil. The
micro-irrigation treatments increased total nitrogen accumulation of the plants,
reduced soil nitrate nitrogen (NO3--N) content at maturity, ensured the nitrogen
supply in the top soil layer, thus increasing NUE. Overall, micro-irrigation with
water and fertilizer as an integrated pattern significantly improved grain yield,
WUE, and NUE of winter wheat in the NCP by co-locating the root, water, and N
fertilizer distribution and reducing NO3--N accumulation in deep soil. The best
treatment was micro-sprinkling irrigation.
PMID- 29940449
TI - Acute peat smoke inhalation sensitizes rats to the postprandial cardiometabolic
effects of a high fat oral load.
AB - Wildland fire emissions cause adverse cardiopulmonary outcomes, yet controlled
exposure studies to characterize health impacts of specific biomass sources have
been complicated by the often latent effects of air pollution. The aim of this
study was to determine if postprandial responses after a high fat challenge, long
used clinically to predict cardiovascular risk, would unmask latent
cardiometabolic responses in rats exposed to peat smoke, a key wildland fire air
pollution source. Male Wistar Kyoto rats were exposed once (1 h) to filtered air
(FA), or low (0.36 mg/m3 particulate matter) or high concentrations (3.30 mg/m3)
of peat smoke, generated by burning peat from an Irish bog. Rats were then fasted
overnight, and then administered an oral gavage of a HF suspension (60 kcal% from
fat), mimicking a HF meal, 24 h post-exposure. In one cohort, cardiac and
superior mesenteric artery function were assessed using high frequency ultrasound
2 h post gavage. In a second cohort, circulating lipids and hormones, pulmonary
and systemic inflammatory markers, and circulating monocyte phenotype using flow
cytometry were assessed before or 2 or 6 h after gavage. HF gavage alone elicited
increases in circulating lipids characteristic of postprandial responses to a HF
meal. Few effects were evident after peat exposure in un-gavaged rats. By
contrast, exposure to low or high peat caused several changes relative to FA
exposed rats 2 and 6 h post HF gavage including increased heart isovolumic
relaxation time, decreased serum glucose and insulin, increased CD11 b/c
expressing blood monocytes, increased serum total cholesterol, alpha-1 acid
glycoprotein, and alpha-2 macroglobulin (p = 0.063), decreased serum
corticosterone, and increased lung gamma-glutamyl transferase. In summary, these
findings demonstrate that a HF challenge reveals effects of air pollution that
may otherwise be imperceptible, particularly at low exposure levels, and suggest
exposure may sensitize the body to mild inflammatory triggers.
PMID- 29940450
TI - Evaluating in situ biodegradation of 13C-labelled naphthenic acids in groundwater
near oil sands tailings ponds.
AB - Potential seepage of naphthenic acids (NAs) from tailings ponds into surface
water and groundwater is one of the main environmental concerns associated with
the Canadian Athabasca oil sands mining operations. Here we report the
application of 13C-labelled NA surrogate compounds to evaluate intrinsic
biodegradation along groundwater flow-paths originating from oil sands tailings
ponds at two different sites: a glacio-fluvial aquifer (Site 1) and a low-lying
wetland (Site 2). Microcosms containing the carboxyl group labelled (99%) NA
surrogates (cyclohexanecarboxylic acid, CHCA; 1,2-cyclohexanedicarboxylic acid,
CHDCA; 1-adamantanecarboxylic acid, ACA) were lowered into monitoring wells for
several months to allow sufficient time for substrate degradation and formation
of a biofilm in conditions characteristic of the local aquifer. Phospholipid
fatty acids (PLFAs), biomarkers for the active microbial population, were
extracted from the biofilms for stable carbon isotope (delta13C) analysis. At
Site 1, highly 13C-enriched delta13C values (up to ~+71000/00) confirmed the in
situ microbial breakdown of CHCA and CHDCA. At Site 2, delta13C-PLFA values from
60.6 to -24.50/00 indicated uptake of a 13C-depleted substrate such as biogenic
methane and not 13C-labelled ACA. Determination of the microbial community using
16s RNA sequencing confirmed the presence of methane-oxidizing bacteria in the
subsurface at Site 2. The in situ biodegradation of NAs at Site 1 demonstrates
that the indigenous microbial population in the shallow subsurface near tailings
ponds can readily break down some of these compounds prior to surface water
discharge. The lack of evidence for microbial uptake of 13C-labelled ACA at Site
2 demonstrates that other NAs, in particular tricyclic diamondoid acids, may
persist in the environment following seepage from tailings ponds or natural
sources.
PMID- 29940451
TI - Global trends in nitrate leaching research in the 1960-2017 period.
AB - Nitrate leaching is the process whereby the nitrate (NO3-) anion moves downwards
in the soil profile with soil water. Nitrate leaching is commonly associated with
chemical nitrogen (N) fertilizers used in agriculture. Nitrate leaching from
different sources and contamination of surface and groundwater is a global
phenomenon that has prompted social and political pressure to reduce nitrate
leaching and contamination of water bodies. This bibliometric study analyzed
global trends in nitrate leaching research. The results showed a rising interest
in the last decades in this topic; given the growth tendency over the last years,
it was envisaged that the importance on nitrate leaching research will continue
increasing in the future. Knowledge on nitrate leaching was mostly disseminated
through scientific publications (90% of total documents recovered), both as
journal articles and reviews, classified in the Scopus database in the
Agricultural, Biological and Environmental Sciences areas. Most publications
dealt with soil nitrogen losses from agroecosystems and farmlands and the
associated impact on the environment; they were published in journals with a
focus on the influence of anthropogenic and soil-crop-animal systems in the
environment, and on how such changes in the environment impact agroecosystems.
Most documents published on nitrate leaching were indisputably from the United
States, followed by China, the United Kingdom and Germany. An analysis of the
main keywords showed an overall dominance of the soil nitrogen cycle, fertilizer
use in agriculture and water quality aspects. The evolution of main crop species
involved in nitrate leaching research showed a rising relevance of research
conducted with maize, wheat and grasses from 1990 onwards. The most productive
institutions in terms of number of documents dealing with nitrate leaching
research, h-index and total citations, were located in the United States, China
and the Netherlands. The United States Department of Agriculture stood out,
followed by the Chinese Academy of Sciences and Wageningen University and
Research. There were clusters of institutions with intercontinental interaction,
on nitrate leaching research, between institutions from Europe, Asia and South
and North America. Overall, this study has highlighted, from a bibliometric
perspective, the rising concern on nitrate leaching. Progress in this field has
been made particularly on the impact of the soil-plant-animal system on the
environment and agroecosystems, and on fundamental and applied aspects of plant
soil interactions with an emphasis in cropping systems.
PMID- 29940452
TI - A time-series study of the association of rainfall, relative humidity and ambient
temperature with hospitalizations for rotavirus and norovirus infection among
children in Hong Kong.
AB - BACKGROUND: Rotavirus and norovirus are infectious pathogens primarily affecting
children under 5 years old. The impact of rainfall on diarrheal diseases remains
inconclusive. This study aimed to evaluate the association between short-term
variation in rainfall, temperature and humidity, and rotavirus and norovirus
hospitalizations among young children in Hong Kong. METHODS: Generalized additive
negative binomial regression models with distributed lag non-linear terms, were
fit with daily counts of hospital admissions due to rotavirus and norovirus
infection as the outcomes and daily total rainfall and other meteorological
variables as predictors, adjusting for seasonality and trend. RESULTS: Generally,
greater rainfall was associated with fewer rotavirus, but more norovirus
hospitalizations. Extreme precipitation (99.5 mm, 99th percentile) was found to
be associated with 0.40 (95% confidence interval (CI) 0.20-0.79) and 1.93 (95% CI
1.21-3.09) times the risk of hospitalization due to rotavirus and norovirus
infection respectively, relative to trace rainfall. Stronger associations were
observed in winter for rotavirus and in summer for norovirus. The duration of
association with rotavirus was notably longer than norovirus. Higher temperatures
were found to be associated with fewer hospitalizations for both rotavirus and
norovirus infection, while higher relative humidity was generally associated with
more norovirus, but fewer rotavirus, hospitalizations. CONCLUSIONS: Both
rotavirus and norovirus hospitalizations were strongly associated with recent
precipitation variation but in opposite directions. With the introduction of the
rotavirus vaccine norovirus is likely to become a greater threat than rotavirus
and thus greater precipitation may become more clearly associated with more
childhood diarrhea.
PMID- 29940453
TI - Examination of the latent structure of DSM-5 posttraumatic stress disorder
symptoms in Slovakia.
AB - The latent structure of posttraumatic stress disorder (PTSD) has been widely
discussed, with the majority of studies in this area being conducted in the US.
The current study aimed to extend this area of research by comparing seven
existing PTSD factor models in a sample of 754 trauma-exposed university students
from Slovakia, where similar research has not been conducted yet. The sample was
predominantly female (83.69%), with a mean age of 22.68 years. The comparison of
competing models revealed that the Anhedonia model, consisting of six inter
correlated factors of reexperiencing, avoidance, negative affect, anhedonia,
dysphoric arousal and anxious arousal, provided the best fit. Several factors of
the Anhedonia model also showed differential relationships with the external
variables of anxiety and depression. The study contributes to the limited
literature on the latent structure of PTSD in Eastern Europe.
PMID- 29940454
TI - Cyberbullying, positive mental health and suicide ideation/behavior.
AB - Cyberbullying has regularly been shown to be associated with suicide
ideation/behavior. The present study investigated whether positive mental health,
i.e., high levels of emotional, cognitive and psychological well-being, buffers
the association between cyberbullying and suicide ideation/behavior. A total of
225 students completed measures of cyberbullying, suicide ideation/behavior, and
positive mental health. Positive mental health fully mediated the association
between cyberbullying and suicide ideation/behavior. Positive mental health seems
to confer resilience and should be taken into account in clinical and preventive
programs for student populations.
PMID- 29940455
TI - Season of birth: A predictor of ADHD symptoms in early midlife.
AB - OBJECTIVE: In this longitudinal study, we applied linear regression analyses to
examine season of birth as related to symptoms of attention deficit/hyperactivity
disorder (ADHD) in early midlife. METHOD: We gathered longitudinal data on a
prospective cohort of community-dwelling men and women (N = 548) followed from
adolescence to early midlife. FINDINGS: The findings indicate that, as compared
with participants who were born in the summer, those who were born in the spring
(Beta = 0.34; t-statistic = 3.59; p < 0.001) had significantly more ADHD
symptoms. In addition, exposure to maternal cigarette smoking in adolescence
significantly intensified (p < 0.01) the association between season of birth and
ADHD symptoms in early midlife. CONCLUSION: These findings suggest that exposure
to greater maternal maladaptive behaviors, such as cigarette smoking, may result
in a greater vulnerability to other environmental risk factors, such as season of
birth.
PMID- 29940456
TI - Premorbid adjustment predictors of cognitive dysfunction in schizophrenia.
AB - Premorbid adjustment (PA) in academic and social domain is a key-predictor of
cognitive performance in schizophrenia. Prior studies provided inconsistent
findings regarding the differential relationships of PA domains with post-illness
cognition. Multivariate associations of academic and social PA in each
developmental stage (childhood, early and late adolescence) with post-onset
cognitive variables were explored. Furthermore, possible differential
relationships of PA domain deterioration courses with post-onset cognitive
dysfunction were investigated. Seventy-five schizophrenia patients were evaluated
with Premorbid Adjustment Scale (PAS). General cognitive ability, verbal IQ,
verbal memory and learning, processing speed, working memory, executive function
and premorbid IQ were assessed. Canonical Correlation Analyses revealed that
poorer academic PA across childhood and early adolescence was related to worse
post-onset verbal IQ, working memory, verbal learning and executive function,
while academic PA deterioration between early and late adolescence was associated
with poorer verbal learning and executive function and, as further analysis
indicated, predicts IQ decline. Academic PA was exclusively associated with post
onset cognitive impairment. New evidence emerged for the specificity of each
developmental period in constructing academic PA in its relation to post-illness
cognition. Early premorbid academic maladjustment possibly constitutes the onset
of a cognitive dysmaturational process which results to post-diagnosis impaired
cognition.
PMID- 29940457
TI - Distribution of ADHD symptoms, and associated comorbidity, exposure to risk
factors and disability: Results from a general population study.
AB - The aim of this study was to examine whether ADHD is a dimensional trait in the
adult general population. We studied whether an increased number of ADHD symptoms
was associated with higher comorbidity, exposure to risk factors (childhood abuse
and parental psychopathology), and disability. We ascertained whether even low
numbers of ADHD symptoms were associated with an increased burden of disease.
Data were used from the second wave of the Netherlands Mental Health Survey and
Incidence Study-2 (NEMESIS-2, N = 5303). NEMESIS-2 is a nationally representative
face-to-face survey on mental health of the Dutch general population. ADHD
symptoms, mental comorbidity, and disability were assessed using the Adult ADHD
Self-Report Scale Screener, the Composite International Diagnostic Interview
version 3.0, and the Medical Outcomes Study Short Form Health Survey,
respectively. Dose-response relationships were found between the number of ADHD
symptoms and Axis I and II mental disorders; exposure to risk factors; and mental
and physical disability. Our study supports the notion that ADHD is a dimensional
trait in the adult general population. Even low numbers of symptoms were
associated with an increased burden of disease, and therefore these should be
identified and treated.
PMID- 29940458
TI - Association between vitamin D deficiency and depression in Nepalese population.
AB - Recent studies link vitamin D deficiency with depression; however evidences from
the Nepalese population are scarce. The current study explored the association
between vitamin D deficiency and depression among 300 adults of 18 years and
above age residing in eastern Nepal. Validated Nepali version of the Beck
Depression Inventory scale (BDI-Ia) was used to determine depressive symptoms and
a BDI cutoff score of >=20 was considered as clinically significant depression.
Sociodemographic data were collected using semi-structured questionnaire. Blood
samples were collected to measure serum 25-hydroxy vitamin D (25(OH)D) and
classify vitamin D status (deficient, insufficient and sufficient). We used Chi
square test to identify the association of sociodemographic variables and vitamin
D status with clinically significant depression. We found a significant
association of gender, geographical location of residence, marital status,
religion and vitamin D status with clinically significant depression. Binary
logistic regression model was used to examine the likelihood of clinically
significant depression among vitamin D deficient individuals. Vitamin D
deficiency was significantly associated with increased odds of clinically
significant depression even after adjusting for confounding variables. This
finding suggests Vitamin D deficient people have increased odds of having
clinically significant depression.
PMID- 29940459
TI - May nesfatin-1 be a state marker in major depressive disorder with suicidal
ideation?
AB - The best known effects of nesfatin-1 are on appetite and metabolic regulation.
Moreover, several research suggest that nesfatin-1 play a role in stress
responses. This molecule may be involved in the pathophysiology of mood disorders
and suicidal behavior. We compared nesfatin-1 levels between depressed patients
with suicidal ideation (n = 32, mean +/- SD, 1,40 +/- 0.11), without suicidal
ideation(n = 31, 1.46 +/- 0.14) and healthy controls (n = 32, 1.52 +/- 0.13).
Suicidal ideation was assessed with the Suicide Probability Scale, Scale for
Suicide Ideation and depressive symptoms were evaluated with the Hamilton
Depression Rating Scale. Blood samples were collected to measure serum nesfatin
1levels by using ELISA method. The study revealed that serum nesfatin-1 levels
were significantly lower in MDD with suicidal ideation than in healthy volunteers
(p < 0.001). There were a negative correlation between the scores of suicidal
ideation and nesfatin-1 levels in MDD with SI group (r = -0.215; p = 0.016). In
the future, nesfatin-1 levels may one day be applied in predicting and monitoring
patients' suicide risk. Further prospective studies are required to elucidate
this potential association.
PMID- 29940460
TI - Lameness scoring and assessment of fitness for transport in dairy cows: Agreement
among and between farmers, veterinarians and livestock drivers.
AB - Cull dairy cows are transported to slaughter, but may be more vulnerable to
transport stress than younger livestock. In order to ensure the welfare of cull
cows during transport their fitness for transport must be assessed before
transport. Lameness is a common reason for culling dairy cows, and assessing
fitness for transport in lame dairy cows is a frequent task for farmers,
veterinarians and livestock drivers. The aim of this study was to evaluate the
agreement within and between these three groups of professionals in relation to
lameness scoring and assessment of fitness for transport. The study used an
online questionnaire consisting of 30 video recordings of walking cows.
Participants were asked to score lameness for each cow and assess if the cow was
fit for transport or not. Weighted and unweighted kappa were used as a measure of
interrater agreement within and between groups. The levels of agreement within
and between the three professional groups were at best moderate. Farmers agreed
less than moderate within their own group as well as compared to veterinarians
and livestock drivers when assessing fitness for transport. In general, it raises
concern that the level of agreement on fitness for transport was moderate or even
lower. These results call for more focus on the assessment of fitness for
transport, including research and possibly training of the different professional
groups in order to ensure good animal welfare during transport.
PMID- 29940461
TI - Aldosterone and aldosterone/cortisol ratio is higher in serum of long-term
compared to first episode schizophrenia patients: A pilot study.
AB - We have previously shown that patients with severe depressive episode exhibit
higher aldosterone concentrations compared to those with moderate depressive
episode. The present study was undertaken to test the hypothesis that circulating
concentration of aldosterone reflect the clinical state in patients with
schizophrenia. The sample consisted of 36 hospitalized patients (25 men, 11
women) with the first episode or long-term course of schizophrenia. The severity
of psychopathology was evaluated using the Positive and Negative Syndrome Scale
(PANSS). Samples for measurement of serum aldosterone were obtained immediately
after awakening. The results showed that serum aldosterone concentrations were
lower in patients with the first episode compared to those in patients with long
term course of schizophrenia. Importantly, lower aldosterone concentrations
observed in patients with the first episode were associated with more severe
clinical symptoms as indicated by all subscales of PANSS. Serum cortisol
concentrations did not differ between the groups, while the aldosterone/cortisol
ratio showed similar pattern as aldosterone concentrations. The present pilot
study suggests that circulating aldosterone in patients with schizophrenia may
reflect the severity of clinical symptoms but in an opposite direction than in
patients with major depressive disorder.
PMID- 29940462
TI - 5-Hydroxypyrido[2,3-b]pyrazin-6(5H)-one derivatives as novel dual inhibitors of
HIV-1 reverse transcriptase-associated ribonuclease H and integrase.
AB - We reported herein the design, synthesis and biological evaluation of a series of
5-hydroxypyrido[2,3-b]pyrazin-6(5H)-one derivatives as HIV-1 reverse
transcriptase (RT) ribonuclease H (RNase H) inhibitors using a privileged
structure-guided scaffold refining strategy. In view of the similarities between
the pharmacophore model of RNase H and integrase (IN) inhibitors as well as their
catalytic sites, we also performed IN inhibition assays. Notably, the majority of
these derivatives inhibited RNase H and IN at micromolar concentrations. Among
them, compound 7a exhibited similar inhibitory activity against RNase H and IN
(IC50RNase H = 1.77 MUM, IC50IN = 1.18 MUM, ratio = 1.50). To the best of our
knowledge, this is the first reported dual HIV-1 RNase H-IN inhibitor based on a
5-hydroxypyrido[2,3-b]pyrazin-6(5H)-one structure. Molecular modeling has been
used to predict the binding mode of 7a in complex with the catalytic cores of HIV
1 RNase H and IN. Taken together these results strongly support the feasibility
of developing HIV-1 dual inhibitors from analog-based optimization of divalent
metal ion chelators. Recently, the identification of dual inhibitors proved to be
a highly effective strategy for novel antivirals discovery. Therefore, these
compounds appear to be useful leads that can be further modified to develop more
valuable anti-HIV-1 molecules with suitable drug profiles.
PMID- 29940463
TI - Design and biological evaluation of novel triaryl pyrazoline derivatives with
dioxane moiety for selective BRAFV600E inhibition.
AB - A series of novel selective BRAFV600E inhibitory agents (Compound 1-16) 5-(2,3
dihydrobenzo[b][1,4]dioxane-6-yl)-N,3-diaryl-4,5-dihydro-1H-pyrazole-1
carbothioamides have been designed and synthesized. Their anti-proliferation and
BRAF inhibitory activities were evaluated. Though 15, 4 and 12 all displayed
comparable activity with the positive control Vemurafenib, only 12 indicated fine
selectivity on BRAFV600E (IC50 = 0.06 MUM for BRAFV600E; GI50 = 0.52 MUM for
A375) over BRAFWT at both kinase and cell levels. This result satisfied the
designing concept of improving activity and introducing selectivity. Flow
cytometry analysis and western blot convinced the apoptosis induction and kinase
inhibitory activity. Docking simulation inferred the differences in binding
patterns of BRAFV600E and BRAFWT, pointing out that the future orientation might
be seeking for outer space binding of BRAFV600E and avoiding interactions with
HIS573 of BRAFWT. These results brought potent BRAF inhibitors one step further
to selective agents, enhancing the potential for safe medication.
PMID- 29940464
TI - Synthesis and biological evaluations of marine oxohexadecenoic acids:
PPARalpha/gamma dual agonism and anti-diabetic target gene effects.
AB - Obesity and associated disorders such as metabolic syndrome and type 2 diabetes
(T2D) have reached epidemic proportions. Several natural products have been
reported as Peroxisome Proliferator-Activated Receptor (PPAR) agonists,
functioning as lead compounds towards developing new anti-diabetic drugs due to
adverse side effects of existing PPAR drugs. We recently isolated and identified
(7E)-9-oxohexadec-7-enoic acid (1) and (10E)-9-oxohexadec-10-enoic acid (2) from
the marine algae Chaetoceros karianus. Herein we report the total synthesis,
pharmacological characterization, and biological evaluations of these naturally
occurring oxo-fatty acids (oFAs). The syntheses of 1 and 2 afforded sufficient
material for extensive biological evaluations. Both oFAs show an appreciable dose
dependent activation of PPARalpha and -gamma, with EC50 values in the micromolar
range, and an ability to regulate important PPAR target genes in hepatocytes and
adipocytes. Moreover, both 1 and 2 are able to drive adipogenesis when evaluated
in the Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cell model, but with
lowered expression of adipocyte markers and reduced lipid accumulation compared
to the drug rosiglitazone. This seems to be caused by a transient upregulation of
PPARgamma and C/EBPalpha expression. Importantly, whole transcriptome analysis
shows that both compounds induce anti-diabetic gene programs in adipocytes by
upregulating insulin-sensitizing adipokines and repressing pro-inflammatory
cytokines.
PMID- 29940465
TI - Discovery and development of novel salicylate synthase (MbtI) furanic inhibitors
as antitubercular agents.
AB - We report on the virtual screening, synthesis, and biological evaluation of new
furan derivatives targeting Mycobacterium tuberculosis salicylate synthase
(MbtI). A receptor-based virtual screening procedure was applied to screen the
Enamine database, identifying two compounds, I and III, endowed with a good
enzyme inhibitory activity. Considering the most active compound I as starting
point for the development of novel MbtI inhibitors, we obtained new derivatives
based on the furan scaffold. Among the SAR performed on this class, compound 1a
emerged as the most potent MbtI inhibitor reported to date (Ki = 5.3 MUM).
Moreover, compound 1a showed a promising antimycobacterial activity (MIC99 = 156
MUM), which is conceivably related to mycobactin biosynthesis inhibition.
PMID- 29940466
TI - Synthesis and antiplasmodial activity of glyco-conjugate hybrids of
phenylhydrazono-indolinones and glycosylated 1,2,3-triazolyl-methyl-indoline-2,3
diones.
AB - A small library of 36 new glycohybrids of phenylhydrazono-indolinones was
synthesized employing glycosylated 1,2,3-triazolyl-methyl-indoline-2,3-diones and
different phenylhydrazines via acid catalyzed reaction. All the compounds were
screened for their antiplasmodial activity in vitro. Compounds 6c, 7c, and 7b
showed significant activity with the IC50 values 1.27, 1.64 and 1.96 MUM,
respectively against CQ sensitive Pf3D7 strain while compounds 7b and 6f showed
good activity with IC50 1.61 and 1.93 MUM, respectively against CQ resistant PfK1
strain.
PMID- 29940467
TI - Induced biotransformation of lead (II) by Enterobacter sp. in SO4-PO4-Cl
solution.
AB - Pb is a toxic heavy metal in contaminated soil and water, resulted from
industrial activities, mine exploration, etc. Phosphate solubilizing bacteria are
able to secrete organic acids and further to enhance the solubility of
phosphates. Enterobacter. sp and geological fluorapatite (FAp) were applied to
investigate the biotransformation of Pb2+ in solution with SO42-, PO43-, and Cl-
species by ICP-OES, ATR-IR, XRD, and SEM. Enterobacter. sp can lower pH of the
medium to ~4. Meanwhile, >90% mobile Pb (declining from 1000 to 30 ppm) was
immobilized via the combination of Enterobacter. sp and FAp. With the addition of
FAp and Pb, pyromorphite was precipitated, but with relatively low content. In
contrast, abundant anglesite mineral was formed in such weakly acidic system.
These anglesite crystals can even absorb phosphates particles onto their surface.
Additionally, geochemical modeling confirms the formation of anglesite and
cerussite under weekly acidic and alkalic condition respectively, especially when
H2PO4- concentration <10-8 mM. Furthermore, the presence of Cl- in solution leads
to the formation of chloropyromorphite when H2PO4- concentration >10-12 mM,
especially under neutral environment. This study explored the biotransformation
of Pb in SO4-PO4-Cl aqueous system and hence provided guidance on bioremediation
of Pb by bacteria and FAp.
PMID- 29940468
TI - The novel early use of dexmedetomidine in the management of tetanus.
PMID- 29940469
TI - Failure of ventilation intra-operatively with NIM EMG endotracheal tube.
PMID- 29940470
TI - Clinical experience of ultrasound-guided single and bi-level erector spinae plane
block for postoperative analgesia in patients undergoing thoracotomy.
PMID- 29940471
TI - Hyperbaric oxygen treatment resistant carbon monoxide poisoning.
PMID- 29940472
TI - Vascular preferential activity of the Pennisetum purpureum cinnamyl alcohol
dehydrogenase promoter in transgenic tobacco plants.
AB - Little is known about the cross talk between the lignin biosynthesis gene
promoters and the regulatory proteins that modulate molecular signaling and
respond to various stresses. In this study, we characterized the promoter region
of the lignin biosynthesis pathway cinnamyl alcohol dehydrogenase (CAD) gene in
elephant grass, Pennisetum purpureum. Quantification of the transcript levels of
the PpCAD promoter revealed it is preferentially expressed in vascular tissue,
especially xylem. Histochemical and fluorometric assays confirmed the vascular
preferential expression of the PpCAD promoter, as the highest beta-glucuronidase
(GUS) activity was found in the basal stem in transgenic tobacco plants
expressing a 1154-bp PpCAD promoter-GUS fusion construct. Moreover, 5'-deleted
PpCAD promoter analyses showed that the 1154-bp PpCAD promoter fragment had the
highest transcriptional activity, whereas the 2054-bp fragment had multifarious
inducible activity responding to gibberellin (GA), methyl jasmonate (MeJA),
abscisic acid (ABA), and wounding. The regions from -248 to -243 bp and -1416 to
1411 bp contained W-box cis-elements, which were detected by electrophoretic
mobility shift assay (EMSA). The binding effects of the GA-responsive elements
(from -561 to -555 bp and -1077 to -1071 bp), MeJA-responsive element (from -1146
to -1142 bp), and the ABA-responsive cis-element (from -1879 to -1874 bp) were
also validated by EMSA. Based on our results, we suggest that lignin deposition
associated with PpCAD promoter activity adapts to the environment through
molecular signaling involving GA, MeJA, and ABA.
PMID- 29940473
TI - Involvement of metabolic, physiological and hormonal responses in the graft
compatible process of cucumber/pumpkin combinations was revealed through the
integrative analysis of mRNA and miRNA expression.
AB - Grafting is a widely used technique, and graft compatibility between the
rootstock and scion is a prerequisite for grafting. To date, the underlying
causes of graft compatibility/incompatibility remain largely unknown. Here, using
cucumber (Cucumis sativus L.) grafted onto pumpkin (Cucurbita L.) rootstocks with
different degrees of graft compatibility, and both self-grafting and non-grafting
as controls, an integrative analysis of mRNA and miRNA expression and regulatory
networks was conducted by using RNA-Seq and sRNA-Seq at 25 days after grafting
(DAG). A total of 223 differentially expressed genes (DEGs) and 30 differentially
expressed miRNAs (DEMs) related to graft compatibility were identified based on
their fold change. Using a combination of GO annotations and KEGG pathway data,
the functional annotations and pathways of DEGs and DEM targets showed that a
number of metabolic, physiological and hormonal responses are involved in graft
compatibility in cucumber leaves including metabolic processes (e.g.,
"carbohydrate metabolic processes"), nutrient transport (e.g., "sugar
transport"), signal transduction (e.g., "MAPK cascade"), plant hormone signal
transduction (e.g., "abscisic acid-activated signaling pathway"), transcription
factors (e.g., MYB, NAC and bHLH), oxidation-reduction processes, and defense
responses. The results of our comprehensive analysis suggested that compatible
rootstocks might possess a greater ability for cell proliferation and a more
efficient carbohydrate metabolism that promotes plant growth. In contrast,
incompatible grafts induced multiple defense response-related genes and various
transcription factors, likely in response to stress. Additionally, they consumed
large amounts of energy, which ultimately restrained the plants normal
development. This study advances our understanding of the molecular mechanisms
underlying plant graft compatible/incompatible responses and provides numerous
mRNA and miRNA candidates for more in-depth studies into the graft compatibility
process.
PMID- 29940474
TI - Methylmercury levels in commonly consumed fish and methylmercury exposure of
children and women of childbearing age in Hong Kong, a high fish consumption
community.
AB - BACKGROUND: Despite high fish consumption levels of Hong Kong residents, little
is known about the MeHg exposure levels of Hong Kong high-risk populations (i.e.
young children and women of childbearing age). OBJECTIVES: To investigate the
MeHg levels in fish commonly consumed in Hong Kong and assess the exposure levels
of local kindergarten children and women of childbearing age. METHODS: A
community-based survey was conducted in randomly recruited local kindergartens.
The MeHg concentrations of the most commonly consumed fish items were measured.
Based on their fish consumption data, subjects' MeHg exposure levels were
estimated and compared with the reference dose (RfD) set by U.S. Environmental
Protection Agency. RESULTS: A total of 2917 mother-child pairs were recruited.
The MeHg levels of the fish samples ranged from < 2-1498.7 ng/g. Six frozen cod
fish samples contained MeHg levels exceeding the local legal limit of 500 ng/g.
The median estimated MeHg intake for children and mothers were 0.29 and 0.22
ug/kg bw/wk, respectively. Approximately 16% children and 9% mothers exceeded the
RfD. CONCLUSIONS: Apart from frozen cod fish, most fish species commonly consumed
in Hong Kong had low MeHg content. Although the majority of our subjects were
exposed to low MeHg levels, high fish consumers could still exceed the RfD and
are potentially at risk of MeHg toxicity. To avoid excessive MeHg exposure, we
suggest that young children and their mothers may consume a variety of locally
available fish, but avoid consumption of frozen cod fish.
PMID- 29940475
TI - A respiratory health survey of a subsurface smoldering landfill.
AB - In late 2010, a subsurface smoldering event was detected in the Bridgeton
Sanitary Landfill in St. Louis County, Missouri. This was followed by complaints
from nearby residents of foul odors emanating from the landfill. In 2016 a health
survey was conducted of residents near the landfill and, as a comparison, other
regions of St. Louis County. The survey was a two-stage cluster sample, where the
first stage was census blocks, and the second stage was households within the
census blocks. The health survey, which was conducted by face-to-face interviews
of residents both near the landfill and away from the landfill, focused mainly on
respiratory symptoms and diseases such as asthma and chronic obstructive
pulmonary disease. The differences in the prevalence of asthma (26.7%, 95% CI
19.8-34.1 landfill vs 24.7%, 95% CI 15.7-33.6 comparison) and COPD (13.7%, 95% CI
7.2-20.3 landfill vs 12.5%, 95% CI 6.4-18.7 comparison) between the two groups
were not statistically significant. Landfill households reported significantly
more "other respiratory conditions," (17.6%, 95% CI 11.1-24.1 landfill vs 9.5%,
95% CI 4.8-14.3 comparison) and attacks of shortness of breath (33.9%, 95% CI
25.1-42.8 landfill vs 17.9%, 95% CI 12.3-23.5). Frequency of odor perceptions and
level of worry about neighborhood environmental issues was higher among landfill
households (p < 0.001). We conclude that the results do not support the
hypothesis that people living near the Bridgeton Landfill have elevated
respiratory or related illness compared to those people who live beyond the
vicinity of the landfill.
PMID- 29940476
TI - Long-term exposure to air pollution and the incidence of multiple sclerosis: A
population-based cohort study.
AB - BACKGROUND: Evidence of the adverse neurological effects of exposure to ambient
air pollution is emerging, but little is known about its effect on the
development of multiple sclerosis (MS), the most common autoimmune disease of the
central nervous system. OBJECTIVES: To investigate the associations between MS
incidence and long-term exposures to fine particles (PM2.5), nitrogen dioxide
(NO2), and ozone (O3) METHODS: We conducted a population-based cohort study to
investigate the associations between long-term exposures to PM2.5, NO2, and O3
and the incidence of MS. Our study population included all Canadian-born
residents aged 20-40 years who lived in the province of Ontario, Canada from 2001
to 2013. Incident MS was ascertained from a validated registry. We assigned
estimates of annual concentrations of these pollutants to the residential postal
codes of subjects for each year during the 13 years of follow-up. We estimated
hazard ratios (HRs) and 95% confidence intervals (CIs) for each pollutant
separately using random-effects Cox proportional hazards models. We conducted
various sensitivity analyses, such as lagging exposure up to 5 years and
adjusting for access to neurological care, annual average temperature, and
population density. RESULTS: Between 2001 and 2013, we identified 6203 incident
cases of MS. The adjusted HR of incident MS was 0.96 (95% CI: 0.86-1.07) for
PM2.5, 0.91(95% CI: 0.81-1.02) for NO2, and 1.09 (95% CI: 0.98-1.23) for O3.
These results were robust to various sensitivity analyses conducted. CONCLUSIONS:
In this large population-based cohort, we did not observe significant
associations between MS incidence and long-term exposures to PM2.5, NO2, and O3
in adults in Ontario, 2001-2013.
PMID- 29940477
TI - Urinary tungsten and incident cardiovascular disease in the Strong Heart Study:
An interaction with urinary molybdenum.
AB - BACKGROUND: Tungsten (W) interferes with molybdenum (Mo) binding sites and has
been associated with prevalent cardiovascular disease (CVD). We evaluated if (1)
W exposure is prospectively associated with incident CVD and (2) the association
between urinary W levels and incident CVD is modified by urinary Mo levels.
METHODS: We estimated multi-adjusted hazard ratios (HRs) for incident CVD
outcomes by increasing W levels for 2726 American Indian participants in the
Strong Heart Study with urinary metal levels measured at baseline (1989-1991) and
CVD events ascertained through 2008. RESULTS: Increasing levels of baseline
urinary W were not associated with incident CVD. Fully-adjusted HRs (95% CIs) of
incident CVD comparing a change in the IQR of W levels for those in the lowest
and highest tertile of urinary Mo were 1.05 (0.90, 1.22) and 0.80 (0.70, 0.92),
respectively (p-interaction = 0.02); for CVD mortality, the corresponding HRs
were 1.05 (0.82, 1.33) and 0.73 (0.58, 0.93), respectively (p-interaction =
0.03). CONCLUSIONS: The association between W and CVD incidence and mortality was
positive although non-significant at lower urinary Mo levels and significant and
inverse at higher urinary Mo levels. Although prior cross-sectional epidemiologic
studies in the general US population found positive associations between urinary
tungsten and prevalent cardiovascular disease, our prospective analysis in the
Strong Heart Study indicates this association may be modified by molybdenum
exposure.
PMID- 29940478
TI - PM10 exposure is associated with increased hospitalizations for respiratory
syncytial virus bronchiolitis among infants in Lombardy, Italy.
AB - Respiratory syncytial virus (RSV) is the primary cause of acute lower respiratory
infections in children, bronchiolitis in particular. Airborne particulate matter
(PM) may influence the children's immune system and foster the spread of RSV
infection. We aimed to verify whether PM10 exposure is associated with
hospitalization due to RSV bronchiolitis. We selected hospital discharge records
(HRD) with ICD-9-CM code 466.11 of infants < 1 year of age, occurring in the
epidemic seasons of two years (2012-2013) in Lombardy, Italy. Cases were assigned
daily PM10 and apparent temperature levels of the capital city of their
residential province. Different exposure windows were considered: single days
preceding hospitalization (lag 0 to 30), their average estimates (lag 0-1 to 0
30), and the four weeks preceding hospitalization (week 1 to 4). Negative
binomial regression models adjusted for apparent temperature and season were
applied to the daily counts of hospitalizations in each province. Results were
expressed as incidence rate ratios (IRR) and 95% confidence intervals (95%CI) per
10 ug/m3 increase in PM10 concentration. Random effects meta-analyses of province
specific IRR were performed to obtain regional estimates. 2814 HRD met our
inclusion criteria; males represented about 55% of the cases. A 6% increased risk
of hospitalization (95%CI: 1.03-1.10) was found at lag 0 and an almost
overlapping 7% increase at lag 1. IRR ranged from 1.03 to 1.05 between lags 2 and
11. No increased risk was observed from lag 12. When considering averaged daily
lags, risk estimates gradually increased in the two weeks preceding
hospitalization from 1.08 (1.04-1.12) at lag 0-1 to 1.15 (1.08-1.23) between lags
0-11 and 0-13. Analyses on weekly lags showed a risk increase of 6% (1.01-1.12)
during week 1 and of 7% (1.02-1.13) during week 2. Our study found a clear
association between short- and medium-term PM10 exposures and increased risk of
hospitalization due to RSV bronchiolitis among infants.
PMID- 29940479
TI - Pathways linking residential noise and air pollution to mental ill-health in
young adults.
AB - BACKGROUND: Recent years have seen growing, but still tentative, evidence of the
potential associations of environmental noise and air pollution with mental
disorders. In the present study, we aimed to examine the associations between
residential noise and air pollution exposures and general mental health in young
adults with a focus on underlying processes METHODS: We sampled 720 students (18
35 years) from one university in the city of Plovdiv, Bulgaria. Residential noise
(LAeq; day equivalent noise level) and air pollution (NO2) were assessed at
participant's residential address by land use regression models. General mental
health was measured with a short form of the General Health Questionnaire (GHQ).
The following putative mediators were considered: annoyance from environmental
pollution, sleep disturbance, restorative quality of the neighborhood,
neighborhood social cohesion, and commuting/leisure time physical activity.
Structural equation modeling was used to analyze the theoretically-indicated
interplay between exposures, mediators, and GHQ. RESULTS: We observed an
association between higher LAeq and GHQ, in which environmental annoyance and
neighborhood restorative quality emerged as key mediators. First, LAeq was
associated with higher annoyance, and through it with lower restorative quality,
and then in turn with lower physical activity, and thus with higher GHQ.
Simultaneously, higher annoyance was associated with higher sleep disturbance,
and thereby with higher GHQ. NO2 had no overall association with GHQ, but it was
indirectly associated with it through higher annoyance, lower restorative
quality, and lower physical activity working in serial. CONCLUSION: We found
evidence that increased residential noise was related to mental ill-health
through several indirect pathways. Air pollution was associated with mental
health only indirectly.
PMID- 29940480
TI - Transcranial magnetic stimulation in hereditary ataxias: Diagnostic utility,
pathophysiological insight and treatment.
AB - Transcranial magnetic stimulation (TMS) is a valuable technique to assess and
modulate human brain function in normal and pathological conditions. This
critical review surveys the contributions of TMS to the diagnosis, insight into
pathophysiology and treatment of genetically confirmed hereditary ataxias, a
heterogeneous group of neurodegenerative disorders that can affect motor cortex
and the corticospinal tract. Most studies were conducted on small sample sizes
and focused on diagnostic approaches. The available data demonstrate early
involvement of the corticospinal tract and motor cortex circuitry, and support
the possible efficacy of cerebellar repetitive TMS (rTMS) as therapeutic
approach. Further TMS-based studies are warranted, to establish biomarkers for
early diagnosis and disease monitoring, explore the involvement of the cerebello
dentato-thalamo-cortical projection, study the effects of rTMS-induced
plasticity, and utilize rTMS for treatment.
PMID- 29940481
TI - The ulnar ratio as a sensitive and specific marker of acute inflammatory
demyelinating polyneuropathy.
AB - OBJECTIVES: To explore the value of a novel sensory criterion, the ulnar ratio -
defined as the SNAP amplitude of the palmar cutaneous (pUN) over that of the
dorsal branch (dUN) of the ulnar nerve - as a predictor of Acute Inflammatory
Demyelinating Polyneuropathy (AIDP). METHODS: We prospectively included 22
patients with AIDP, 20 patients with diabetic peripheral neuropathy (DPN), and 18
controls. Eligible subjects underwent nerve conduction studies including, among
others, the dUN, pUN, and sural nerve. RESULTS: A sural sparing pattern was found
in 72% of AIDP cases. The ulnar ratio was significantly lower in patients with
AIDP compared to those with DPN or controls. The ROC curve area to discriminate
AIDP (versus controls and diabetics together) was higher with the ulnar ratio and
pUN compared to dUN. An ulnar ratio >= 0.78 seems to be the best threshold to
rule out the diagnosis of AIDP, with a specificity of 100% and a sensitivity of
87%. The ulnar ratio was equally reliable in the subgroup of patients presenting
within a week of symptoms onset. CONCLUSION: The ulnar ratio is a highly
sensitive and specific marker of AIDP and can help confirm the diagnosis when
direct signs of demyelination are lacking. SIGNIFICANCE: Incorporating specific
sensory abnormalities, such as the ulnar ratio, in the electrodiagnostic criteria
of AIDP could enhance their reliability.
PMID- 29940482
TI - The effect of walking path configuration on gait in adults with Alzheimer's
dementia.
AB - BACKGROUND: Walking is a cognition intensive activity and impaired walking is
associated with an increased fall risk in people with Alzheimer's dementia (AD).
Walking in a curved path configuration increases complexity of the task, reflects
real-life environments and situations when falls occur. The effect of walking
path task complexity has not been evaluated in people with AD. RESEARCH QUESTION:
The purpose was 1) to assess the utility of a curved path walking task to detect
differences in gait performance between people with AD and healthy controls and
2) to assess the relationship of cognitive function to gait performance on
straight path and curved path walking. METHODS: Participants with AD (n = 14,
mean age +/- SD = 73.08 +/- 9.22) and age and sex matched controls (n = 14, mean
age = 72.86 +/- 9.53) were recruited. Time to complete a 6-meter straight path
and a curved path (Figure of 8 Test) walking task was recorded. Steps taken,
accuracy and qualitative measures of smoothness were rated for curved-path
walking. Measures of global cognition (MMSE, MoCA) and executive function (Trail
making A and B, Digit Span forwards and backwards) were assessed. RESULTS: Gait
was significantly slower in people with AD for both the straight-path (AD = 6.05
+/- 1.26 s, Control = 5.09 +/- 0.76 s, p = 0.02) and curved-path walking (AD =
11.25 +/- 4.87 s, Control = 8.28 +/- 2.44 s, p = 0.05). In addition, smoothness
scores were significantly lower for people with AD (AD = 1.93+/-1.26; Control =
3.00+/-0.00, p = 0.004). SIGNIFICANCE: Walking in a curved path resulted in a
significant deterioration in gait quality in the people with AD. Executive
function was related only to curved path walking, in which lower executive
function scores were associated with longer time to walk.
PMID- 29940483
TI - Relationships between walking speed, T-score and age with gait parameters in
older post-menopausal women with low bone mineral density.
AB - BACKGROUND: The gait patterns of women with low bone mineral density (BMD) or
osteoporosis have not been thoroughly explored, and when examined, often studied
in relation to falls and kyphosis. RESEARCH QUESTION: The aim of this study was
to investigate the relationships between gait parameters and comfortable, self
selected walking speed and BMD in older post-menopausal women with a broad range
of T-scores (healthy to osteoporotic). METHODS: 3D kinematic and kinetic data
were collected from forty-five women mean (SD) age 67.3 (1.4) years during level
walking at their preferred speed. Multiple regression analyses explored the
explained variance attributable to speed, femoral neck T-score, and age. RESULTS:
The mean (SD) walking speed 1.40 (0.19) m.s-1 explained the variance in most
temporal-spatial, kinematic and joint powers (R2 = 12-68%, P <= 0.01). T-score
accounted for (R2 = 23%, P <= 0.001) of the shared explained variance in stride
width. It also increased the explanatory power for knee flexion (R2 = 7%, P <=
0.05) and knee range of motion (R2 = 12%, P <= 0.01). Power absorption by the
knee flexors in terminal swing (K4) was the only power burst resulting in
significant slope coefficients for all predictor variables (R2 = 52 and 54%) (P
<= 0.001) and (R2 = 68%, P <= 0.05). SIGNIFICANCE: Speed alone explained most of
the variance in the gait parameters, while speed and T-score combined increased
the explanatory power of the regression models for some of the knee joint
variables. Our findings demonstrated that older post-menopausal women, with a
broad range of T-scores, are able to walk at comfortably fast speeds, generating
gait patterns similar to those of younger women. The results also suggest that
strengthening the hip abductor, knee extensor and flexor muscle groups may
benefit the gait patterns of older postmenopausal women with low BMD.
PMID- 29940484
TI - The linguistic constraint on contraction in children with SLI.
AB - PURPOSE: The goal of the present study was to investigate whether children with
specific language impairment (SLI) obey the constraint on contraction with the
verb BE in three linguistic contexts: ellipsis, yes/no questions and embedded
questions. METHOD: Using elicited production methodology, a total of 51 children
were tested: 17 children with SLI (mean age = 5;6); 17 language-matched children
matched on mean length of utterance (mean age = 3;6) and 17 children age-matched
children (mean age = 5;4). RESULTS: The experimental results revealed that
children with SLI did not differ from the children in the control groups.
Children contracted BE where it is possible and failed to contract in the
linguistic contexts where contraction is prohibited. Our experimental findings
suggest that for this aspect of linguistic knowledge children with SLI have the
same underlying grammar as children whose grammars are typically-developing.
PMID- 29940485
TI - Weibo friends with benefits for people live with HIV/AIDS? The implications of
Weibo use for enacted social support, perceived social support and health
outcomes.
AB - With the increasing popularity of social media, many people who live with
HIV/AIDS (PLWHA) seek social support via Weibo in China. The question arises here
as to whether PLWHA perceive higher levels of social support via Weibo than in
offline relationships, whether perceived online social support (PSS-ON) is
associated with enacted social support, and whether it is effective in predicting
better health outcomes. Based on self-reported data from 432 Chinese PLWHA, the
authors investigated perceived offline social support (PSS-OFF), PSS-ON, enacted
social support, and health outcomes. The empirical results indicate that PSS-ON
is significantly associated with employment status, CD4 cell counts, and PSS-OFF.
PSS-ON is higher than PSS-OFF for PLWHA, and close Weibo friends are the main
source of PSS-ON. Enacted receiving social support and giving social support are
relevant, and they contribute as individual predictors of PSS-ON. PSS-ON and PSS
OFF are distinct constructs in predicting the subjective well-being of PLWHA,
while PSS-ON is not related to adherence to antiretroviral therapy (ART) and
risky sexual behavior in this study. Limitations and future directions are
discussed.
PMID- 29940486
TI - Pharmacophore modeling, molecular docking and molecular dynamics simulations
toward identifying lead compounds for Chk1.
AB - Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase, plays an important
role in G2/M checkpoint, which is a key regulator in response to DNA damage. In
this study, the structure-based drug design approach and molecular dynamics (MD)
simulations were used to explore potent Chk1 inhibitors. A series of the best
fitting candidates were picked out from the Specs database. Out of these, five
candidates were submitted for MD simulations to explore the stability of complex.
The result indicates that these five candidates could be considered potential
Chk1 inhibitors and represents a promising starting point for developing potent
inhibitors of Chk1 for the treatment of tumor.
PMID- 29940487
TI - Discovering space - Grounding spatial topology and metric regularity in a naive
agent's sensorimotor experience.
AB - In line with the sensorimotor contingency theory, we investigate the problem of
the perception of space from a fundamental sensorimotor perspective. Despite its
pervasive nature in our perception of the world, the origin of the concept of
space remains largely mysterious. For example in the context of artificial
perception, this issue is usually circumvented by having engineers pre-define the
spatial structure of the problem the agent has to face. We here show that the
structure of space can be autonomously discovered by a naive agent in the form of
sensorimotor regularities, that correspond to so called compensable sensory
experiences: these are experiences that can be generated either by the agent or
its environment. By detecting such compensable experiences the agent can infer
the topological and metric structure of the external space in which its body is
moving. We propose a theoretical description of the nature of these regularities
and illustrate the approach on a simulated robotic arm equipped with an eye-like
sensor, and which interacts with an object. Finally we show how these
regularities can be used to build an internal representation of the sensor's
external spatial configuration.
PMID- 29940488
TI - Lp- and Ls-Norm Distance Based Robust Linear Discriminant Analysis.
AB - Recently, L1-norm distance measure based Linear Discriminant Analysis (LDA)
techniques have been shown to be robust against outliers. However, these methods
have no guarantee of obtaining a satisfactory-enough performance due to the
insufficient robustness of L1-norm measure. To mitigate this problem, inspired by
recent works on Lp-norm based learning, this paper proposes a new discriminant
method, called Lp- and Ls-Norm Distance Based Robust Linear Discriminant Analysis
(FLDA-Lsp). The proposed method achieves robustness by replacing the L2-norm
within- and between-class distances in conventional LDA with Lp- and Ls-norm
ones. By specifying the values of p and s, many of previous efforts can be
naturally expressed by our objective. The requirement of simultaneously
maximizing and minimizing a number of Lp- and Ls-norm terms results in a
difficulty to the optimization of the formulated objective. As one of the
important contributions of this paper, we design an efficient iterative algorithm
to address this problem, and also conduct some insightful analysis on the
existence of local minimum and the convergence of the proposed algorithm.
Theoretical insights of our method are further supported by promising
experimental results on several images databases.
PMID- 29940489
TI - On the importance of hidden bias and hidden entropy in representational
efficiency of the Gaussian-Bipolar Restricted Boltzmann Machines.
AB - In this paper, we analyze the role of hidden bias in representational efficiency
of the Gaussian-Bipolar Restricted Boltzmann Machines (GBPRBMs), which are
similar to the widely used Gaussian-Bernoulli RBMs. Our experiments show that
hidden bias plays an important role in shaping of the probability density
function of the visible units. We define hidden entropy and propose it as a
measure of representational efficiency of the model. By using this measure, we
investigate the effect of hidden bias on the hidden entropy and provide a full
analysis of the hidden entropy as function of the hidden bias for small models
with up to three hidden units. We also provide an insight into understanding of
the representational efficiency of the larger scale models. Furthermore, we
introduce Normalized Empirical Hidden Entropy (NEHE) as an alternative to hidden
entropy that can be computed for large models. Experiments on the MNIST, CIFAR-10
and Faces data sets show that NEHE can serve as measure of representational
efficiency and gives an insight on minimum number of hidden units required to
represent the data.
PMID- 29940490
TI - Corrigendum to 'Immunomodulatory effect of new quinolone derivative against
cisplatin/gamma radiation-induced renal and brain toxicity in mice' [J.
Photochem. Photobiol. B Biol., 184 (2018) 54-60].
PMID- 29940491
TI - Characterization of degeneration phenomena in lithium-ion batteries by combined
microscopic techniques.
AB - The application of detector strategies in scanning electron microscopy (SEM)
correlated with computer tomography (CT) and light microscopy (LM) delivered
unique new insights in degeneration effects of lithium-ion batteries. There we
exemplary studied reference, cycled and storage cells. High-resolution SEM permit
to visualize a coating on top of the cathode material of the treated cells for
the first time, which also connects the conductive additives and battery active
material. This confirms the assumption of a solid permeable interface on top of
the cathode. The detection of low-loss reflected backscattered electrons for
energies beyond 3 keV increases the available spatial resolution for material
contrast. This offered the opportunity to address the atomic number of
precipitates in the nm range inside the coating to be above carbon and below Li1
x(Ni1/3Mn1/3Co1/3)O2 (NMC). Applying voltage contrast enables to show the
difference in electronic conductivity of plate-like features on top of the cycled
cell anode, most likely lithium plating. Cross sectional images of the anode
delivered a significant change of the surficial-area morphology for the treated
cells with increasing porosity. Precipitates were detected on top of the
separator foil. An increment in thickness of the entire treated cells by computer
tomography was found, which can be explained by the alteration of the anode,
separator and cathode.
PMID- 29940492
TI - Unraveling CYP2E1 haplotypes in alcoholics from Central Brazil: A comparative
study with 1000 genomes population.
AB - We evaluated genetic variability of single nucleotide polymorphisms (SNPs)
situated in the CYP2E1 gene promoter in alcoholics. We also compared 1000 Genomes
Project of CYP2E1 polymorphisms with frequencies of genotypes and haplotypes.
Eight variation points were exclusively found in Brazilians. The allelic
distributions of the rs3813867, rs2031920 and rs2031921 polymorphisms in the
CYP2E1 showed that the wild alleles (G, C, T, respectively) had higher
frequencies in both groups, alcoholic (96%, 96%, 96%) and a control group (95.8%,
94.9%, 94.9%), when compared to the mutated allele (C, T, C, respectively). The
variation points, rs3813867, rs2031920 and rs2031921 showed strong linkage
disequilibrium (LOD >= 2, D ' = 1). South Asian populations presented larger LD
blocks compared to the other populations. Our results showed that the allelic
frequencies were markedly different among ethnicities and have contributed to the
knowledge regarding the distribution among ethnic groups, being associated to
alcohol consumption worldwide.
PMID- 29940493
TI - Additional insight into biarticular muscle function: The influence of hip flexor
fatigue on rectus femoris activity at the knee.
AB - We evaluated the compensatory adaptations in muscle regionalization and synergist
activity after fatiguing a biarticular muscle at one joint with different muscle
lengths. Eleven men (mean +/- SD age = 23 +/- 3 years) performed 50 maximal
concentric isokinetic contractions of the dominant hip flexors on two occasions.
For one trial, the knee joint was fully extended. For the other, the knee joint
was fixed at 70 degrees . Maximal voluntary contractions of the knee extensors
were performed immediately before and after the hip flexion fatigue protocol
while bipolar surface electromyographic signals were detected from the vastus
lateralis and at five points along the length of the rectus femoris. Regardless
of knee joint angle during the hip flexion fatigue protocol, knee extension peak
torque was unchanged following hip flexion fatigue. Electromyographic amplitude
for the vastus lateralis (p = .047, eta2 = .338) and rectus femoris (p < .001,
eta2 = .667) showed main effects for time, indicating higher and lower post
fatigue values, respectively. There was no evidence of region-specific rectus
femoris adaptations during extension at the knee following fatigue of the hip
flexors. These data suggest that synergistic adaptations were involved in
maintaining knee extension peak torque following hip flexion fatigue.
PMID- 29940494
TI - Gait evaluation using inertial measurement units in subjects with Parkinson's
disease.
AB - We investigated whether a wearable system based on a commercial Inertial
Measurement Unit (IMU) can reliably provide the main spatiotemporal gait
parameters in subjects with Parkinson's disease (PD), compared to a gold-standard
optoelectronic motion capture system. The gait of 22 subjects with PD (Age: 69.4
(6.1) years; UPDRS-III: 28.0 (9.2)) was recorded simultaneously with an
optoelectronic system and a commercial IMU-based wearable system. Eight
spatiotemporal parameters describing the step cycle (cadence, velocity, stride
length, stride duration, step length, stance, swing and double support duration)
were compared between the two systems. The IMU and the optical system reported
comparable gait parameters, with the exception of walking velocity (optical
system, 0.72 (0.27) m?s-1 vs. IMU: 0.86 (0.26) m?s-1, p < 0.05). Although most
parameters detected by the two systems were not statistically different, some of
them like stride length, double support and step duration showed notable root
mean square and mean absolute errors. In conclusion, the algorithm embedded in
the current release of the commercial IMU requires further improvements to be
properly used with subjects with PD. Overall, the IMU system was sufficiently
accurate in the assessment of fundamental gait spatiotemporal parameters. The
fast and simplified data recording process allowed by wearables makes this
technology appealing and represents a possible solution for the quantification of
gait in the clinical context, especially when using a traditional 3D
optoelectronic gait analysis is not possible, and when subjects are not fully
cooperative.
PMID- 29940495
TI - A rapid and sensitive LC-MS/MS method for quantitative analysis of cardiolipin
(18:2)4 in human leukocytes and mouse skeletal muscles.
AB - A rapid and sensitive LC-MS/MS method has been developed for quantitative
analysis of cardiolipin (18:2)4 or CL (18:2)4 in human leukocytes and mouse
mitochondria. The structural analog CL (14:0)4 was used as the internal standard.
Both CL (18:2)4 and the IS were extracted using a modified Folch method, and
separated on a Waters XBridge(r) BEH C18 XP column using a mobile phase of 0.1%
ammonium hydroxide in acetonitrile/water (90:10, v/v) pumped at a flow rate of
0.4 mL/min. Quantitation was achieved by negative ESI-MS/MS in MRM mode. The
total run time was 2.00 min with retention times of 0.74 min for the IS and 0.84
min for CL (18:2)4, respectively. The method was validated according to the US
FDA guidance for bioanalytical method validation using human leukemia and
lymphoma cell lines, which had a calibration range of 0.120-60.2 nM with a
correlation coefficient >0.999. The intra- and inter-assay accuracy and precision
were <=+/-5% and <=8%. The IS normalized matrix factors of CL (18:2)4 and the IS
normalized recoveries of CL (18:2)4 ranged 0.92-1.04, and 95-101%, respectively.
The stability studies showed that CL (18:2)4 was stable under various test
conditions. The developed method was successfully applied to the measurement of
CL (18:2)4 in various biological samples including K562 and HL-60 human leukemia
cell lines, U937 human lymphoma cell line, white blood cells from patients of
Alzheimer's disease and normal cognitive controls (NCCs), and mitochondria from
mouse skeletal muscles. It may be useful for preclinical and clinical studies of
this compound.
PMID- 29940496
TI - Recent advances in the capillary electrophoresis analysis of antibiotics with
capacitively coupled contactless conductivity detection.
AB - This review describes briefly the high rate of counterfeiting of antimicrobial
drugs with focus upon its immediate health consequences. The major part of this
review encompasses accounts of the improvements achieved in the domain of
miniaturization of capillary electrophoresis with capacitively coupled
contactless conductivity detection (CE-C4D). The application of this principle
into the development of portable devices as well as its application to counter
the health-system-crippling phenomenon of counterfeit antibiotic formulations,
are discussed in the context of developing countries.
PMID- 29940497
TI - Receptor conversion in breast cancer brain metastases may affect survival.
PMID- 29940498
TI - The value of 3D images in the aesthetic evaluation of breast cancer conservative
treatment. Results from a prospective multicentric clinical trial.
AB - PURPOSE: BCCT.core (Breast Cancer Conservative Treatment. cosmetic results) is a
software created for the objective evaluation of aesthetic result of breast
cancer conservative treatment using a single patient frontal photography. The
lack of volume information has been one criticism, as the use of 3D information
might improve accuracy in aesthetic evaluation. In this study, we have evaluated
the added value of 3D information to two methods of aesthetic evaluation: a panel
of experts; and an augmented version of the computational model - BCCT.core3d.
MATERIAL AND METHODS: Within the scope of EU Seventh Framework Programme Project
PICTURE, 2D and 3D images from 106 patients from three clinical centres were
evaluated by a panel of 17 experts and the BCCT.core. Agreement between all
methods was calculated using the kappa (K) and weighted kappa (wK) statistics.
RESULTS: Subjective agreement between 2D and 3D individual evaluation was fair to
moderate. The agreement between the expert classification and the BCCT.core
software with both 2D and 3D features was also fair to moderate. CONCLUSIONS: The
inclusion of 3D images did not add significant information to the aesthetic
evaluation either by the panel or the software. Evaluation of aesthetic outcome
can be performed using of the BCCT.core software, with a single frontal image.
PMID- 29940499
TI - Fabrication and characterization of hydrophilic corn stalk biochar-supported
nanoscale zero-valent iron composites for efficient metal removal.
AB - Pyrolyzing low-cost agro-waste into biochar is a promising means for waste
biomass utilization. This study engineers corn stalk-derived biochar with
abundant hydrophilic functional groups as a support material for iron
nanoparticles impregnation (nZVI-HCS). Surface chemistry and morphology of nZVI
HCS composites is characterized by SEM, TEM, TG, XRD, FTIR, XPS, and BET
techniques, which helps to elucidate the mechanisms of Pb2+, Cu2+ and Zn2+
removal from single and mixed-metal solutions in batch experiments. Equilibrium
adsorption capacities can reach 195.1, 161.9 and 109.7 mg.g-1 for Pb2+, Cu2+ and
Zn2+ at neutral medium after 6-h process, respectively. The engineered biochar
with hierarchical pores can impregnate iron nanoparticles, serve as an adsorbent,
and enhance metal reduction/precipitation. Rapid removal and high performance can
be maintained after five regeneration/reuse cycles. Multiple interaction
mechanisms including adsorption, precipitation, reduction and complexation are
responsible for metal removal by nZVI-HCS composites, which can be a novel
biowaste-derived material for wastewater treatment.
PMID- 29940500
TI - The role of formulation and follicular pathway in voriconazole cutaneous delivery
from liposomes and nanostructured lipid carriers.
AB - In general, colloids provide increased cutaneous permeation of drugs. Still, skin
interaction and main pathways for drug diffusion may vary depending on system and
formulation characteristics. The knowledge of how different colloidal systems
interact with biological membranes and the formulation impact on delivery is
especially relevant for drugs that can be encapsulated in multiple nanosystems,
as voriconazole (VOR). In here, we compared VOR release and permeation profile
from liposomes (LP) and nanostructured lipid carriers (NLC) in aqueous colloidal
dispersions and in gel formulations. Despite the controlled drug release provided
by gel formulations, formulation only had a significant impact on drug skin
accumulation from LP. The reduced mobility in gel formulations compromised
follicle deposition and drug retention in the skin. Such a hypothesis was
confirmed by permeation experiments evaluating follicle pathway influence.
Follicular route also had an influence on delivery from NLC, which was only
significant for total drug that reached the acceptor medium. These differences
could be attributed to the mechanisms of colloid interaction with the skin and
subsequent drug release. Follicle LP deposition and slow drug release leads to
higher cutaneous amounts whilst NLC interaction with skin and fast drug release
leads to fast drug diffusion and deeper penetration. By the low MIC50 values
encountered against Trichophyton rubrum (~ 0.001 MUg/mL), permeated amounts could
inhibit fungal growth, regardless the system. In conclusion, both LP and NLC seem
to be valuable systems for cutaneous VOR delivery. Fluidic formulations could
provide better efficiency for cutaneous drug delivery from LP.
PMID- 29940501
TI - Enhanced antibacterial activity of carbon dots functionalized with ampicillin
combined with visible light triggered photodynamic effects.
AB - In the last years, carbon-based nanomaterials have attracted considerable
attention in a wide range of fields, particularly in biomedicine, owing to their
remarkable photo-physical and chemical properties. In this study, we demonstrate
that amine-terminated carbon dots (CDs-NH2) functionalized with ampicillin (AMP)
offer a new perspective for antibacterial treatment. The amine-functionalized
carbon dots were used as a carrier for immobilization and delivery of ampicillin
(CDs-AMP) and as a visible light-triggered antibacterial material. Additionally,
AMP immobilization on the CDs-NH2 surface improves its stability in solution as
compared to free AMP. The AMP conjugated CDs platform combines the antibacterial
function of AMP and conserves the intrinsic theranostic properties of CDs-NH2.
Therefore, the AMP immobilized onto CDs-NH2 surface together with the generation
of moderate quantities of reactive oxygen species under visible light
illumination are very effective to inactivate the growth of Escherichia coli.
PMID- 29940502
TI - Facile preparation of biocompatible nanostructured lipid carrier with ultra-small
size as a tumor-penetration delivery system.
AB - Insufficient tumor penetration is one of the major obstacles for satisfactory
cancer therapy. As a result, the ability to push the lower limits of size for
nanoparticle platforms that have traditionally existed in larger forms is highly
desirable. In our study, a facile solvent diffusion method was applied to prepare
an ultra-small nanostructured lipid carrier (usNLC) which was capable of
encapsulating hydrophobic molecules. Our results demonstrate that the as-prepared
usNLC is composed of homogeneous particles with size around 25 nm. In addition to
its preferable colloidal stability, negligible hemolysis as well as strong tumor
homing property, the as-prepared usNLC shows preferable tumor penetration
capacity both in vitro and in vivo. The paclitaxel (PTX) loaded usNLC shows
comparable in vitro cytotoxicity on HepG2 cells and multicellular tumor spheroids
to Taxol with the best in vivo anti-tumor efficacy, which all indicate its
potential to be a promising candidate for cancer therapy.
PMID- 29940503
TI - Polysaccharide-based cationic hydrogels for dye adsorption.
AB - With advances in soft material design and engineering, naturally resourced
polysaccharides have frequently been used to construct hydrogels because of their
unique properties such as renewability, biodegradability and biocompatibility. In
this work, we use a water-soluble microbial polysaccharide, salecan as a trapped
natural polymer, poly(acrylamide-co-diallyldimethylammonium chloride) (PAD) as a
functional matrix to prepare salecan/PAD hydrogels through a facile one-pot
method. We employed a variety of spectroscopic techniques to probe the
physicochemical properties of the designed hydrogels. The results demonstrated
that salecan not only tuned the polarity of the PAD hydrogels, but also endowed
them with adjustable water content. Subsequently, the adsorption performance of
these hydrogels to methyl orange (MO) dye was investigated in detail. It was
found that the salecan/PAD had the ability to remove MO from the surrounding
aqueous solutions. In addition, adsorption kinetic data were nicely described by
pseudo-second-order model and the adsorption isotherm data fitted well with the
Freundlich equation. Having tailorable physicochemical properties coupled with
the ability to uptake dye, these salecan-incorporated hydrogels could be
promising platform for wastewater treatment and removal of heavy metal ions.
PMID- 29940504
TI - Reduction/temperature/pH multi-stimuli responsive core cross-linked polypeptide
hybrid micelles for triggered and intracellular drug release.
AB - The high toxicity, poor stability, premature drug release, and lack of
intracellular stimuli responsibility of current polymeric micelles still hinder
them for potential clinical applications. To address these challenges, a novel
type of multi-stimuli responsive, core cross-linked polypeptide hybrid micelles
(CCMs) was developed for triggered anticancer drug delivery in tumor
microenvironment. The CCMs was prepared via free radical copolymerization by
using N,N'-methylene-bis-acylamide (BACy) as the cross-linking agent, 2,2
azobisisobutyronitrile (AIBN) as the initiator, where poly (gamma-benzyl-L
glutamate) (PBLG) and N-isopropylacrylamide (NIPPAM) as comonomers. The
doxorubicin (DOX) was then introduced into the CCMs by hydrazone bond to prepare
the drug-incorporated core cross-linked micelles (CCMs-DOX). By the experimental
results, the CCMs showed reduction responsibility due to the degradable disulfide
bond in the polymer network. The hydrazone bond can be broken under acidic
condition causing a controllable drug release for CCMs-DOX. Compared to only 7.7%
DOX release under pH 7.4 at 37 degrees C, a much higher DOX release rate up to
85.3% was observed under 10 mM GSH (pH 5.0, 42 degrees C). In vitro cell assays
showed that the blank CCMs showed almost no toxicity against HUVEC cells while
the CCMS-DOX exhibited significant cancer cell killing effect. These experimental
results suggested that the prepared multi-stimuli responsive polymeric micelles
could serve as a smart and promising drug delivery candidate for anti-cancer
therapy.
PMID- 29940505
TI - Boron fullerenes, Bn (n=20, 30, 38, 40, 50, 60): First principle calculations of
electronic and optical properties.
AB - Density functional theory (DFT) and time dependent density functional theory
(TDDFT) at PBE0/6-311G* level are performed to examine the stability, electronic
and optical properties of boron fullerenes (Bn, n = 20, 30, 38, 40, 50, 60).
Amongst all the structures, B50 is found to be highly stable and has the least
electronic gap. In general, all borofullerenes are found to be semiconducting in
nature. Absorption wavelength shift in the photoabsorption spectra is reported
with the increasing borofullerene size. Furthermore, the maximum absorption
occurs within the visible range (for n = 30-50) characterized by deeper level
excitations. Upon absorption, the electron delocalization is found to increase
with the borofullerene, from natural transition orbital analysis (NTO) and
exciton size analysis, respectively. Exciton size determination indicates a
linear relationship between the number of borofullerene atoms and the exciton
size. The excitons have been found to be Frenkel in nature.
PMID- 29940506
TI - Visualizing convolutional neural network protein-ligand scoring.
AB - Protein-ligand scoring is an important step in a structure-based drug design
pipeline. Selecting a correct binding pose and predicting the binding affinity of
a protein-ligand complex enables effective virtual screening. Machine learning
techniques can make use of the increasing amounts of structural data that are
becoming publicly available. Convolutional neural network (CNN) scoring functions
in particular have shown promise in pose selection and affinity prediction for
protein-ligand complexes. Neural networks are known for being difficult to
interpret. Understanding the decisions of a particular network can help tune
parameters and training data to maximize performance. Visualization of neural
networks helps decompose complex scoring functions into pictures that are more
easily parsed by humans. Here we present three methods for visualizing how
individual protein-ligand complexes are interpreted by 3D convolutional neural
networks. We also present a visualization of the convolutional filters and their
weights. We describe how the intuition provided by these visualizations aids in
network design.
PMID- 29940507
TI - Insulin deprivation decreases insulin degrading enzyme levels in primary cultured
cortical neurons and in the cerebral cortex of rats with streptozotocin-induced
diabetes.
AB - BACKGROUND: Many studies have indicated a relationship between diabetes and
Alzheimer's disease (AD). However, the molecular mechanism underlying this
association has not been clarified. Among several factors, insulin degrading
enzyme (IDE), which plays roles in the degradation of both insulin and amyloid
beta (Abeta), has gained interest as a potential target in efforts to solve this
puzzle. This study sought to examine the effects of varying insulin and/or
glucose concentrations on IDE expression. METHODS: Experiments were performed on
primary cultured rat neurons and cortices of rats with streptozotocin (STZ)
induced diabetes. IDE protein and mRNA expression levels were measured by western
blot and RT-PCR, respectively. RESULTS: In primary cultured cortical neurons,
removal of insulin for 5days reduced the expression of IDE. A five-day treatment
with a high concentration of glucose in insulin-free media reduced IDE levels,
while a high concentration of glucose in the presence of insulin had no effect.
In groups treated with glucose or insulin intermittently, the reduction in IDE
levels was observed only in neurons exposed to high glucose together with no
insulin for 5days. Shorter incubation periods (48h), either continuously or
intermittently, did not affect IDE levels. IDE expression in the cortex of rats
with STZ-induced diabetes was found to be decreased. CONCLUSION: Our data suggest
that insulin deprivation, rather than high glucose, is a significant determinant
of IDE regulation. As evidence indicates potential roles for IDE in diabetes and
AD, understanding the mechanisms regulating IDE expression may be important in
developing new treatment strategies.
PMID- 29940508
TI - Chronic treatment with a MEK inhibitor reverses enhanced excitatory field
potentials in Syngap1+/- mice.
AB - BACKGROUND: Synaptic Ras-GTPase-activating protein 1 (SYNGAP1) is an abundant
brain-specific protein localized at the postsynaptic density of mammalian
excitatory synapses. SYNGAP1 functions as a crucial regulator of downstream
intracellular signaling triggered by N-methyl-d-aspartate receptor activation.
One of the most important signaling pathways regulated by SYNGAP1 is the Ras-Raf
MEK-ERK pathway. SYNGAP1 deficiency is associated with hyperphosphorylation of
MEK and ERK kinases and with altered synaptic function in Syngap1+/- mice. Loss
of-function mutations in the SYNGAP1 gene have been documented in many human
cognitive and neurological disorders. However, there are currently no approaches
that reverse the phenotypes of SYNGAP1 deficiency. METHODS: Using
electrophysiological recordings of field responses in hippocampal slices, we
examined if disturbances of synaptic physiology in the hippocampus of 7-8-month
old Syngap1+/- mice were sensitive to the effect of the MEK inhibitor PD-0325901
given orally for 6days. RESULTS: We found that in hippocampal slices from vehicle
treated Syngap1+/- mice, basal synaptic responses were higher and their long-term
potentiation (LTP) was lower than in slices from wild-type littermates. Chronic
administration of PD-0325901 normalized basal synaptic responses, but did not
reverse LTP deficit. CONCLUSIONS: The differential sensitivity of basal synaptic
transmission and LTP to MEK inhibition indicates that the effects of SYNGAP1
deficiency on these synaptic parameters are mediated by distinct pathways. Our
findings also suggest that at least some physiological phenotypes of the germline
Syngap1 mutation can be ameliorated by pharmacological treatment of adult
animals.
PMID- 29940510
TI - One-step synthesis of reduced graphene oxide sheathed zinc oxide nanoclusters for
the trace level detection of bisphenol A in tissue papers.
AB - After a long-term toxicity study on Bisphenol A (BPA), the European Union and U.S
food and drug administration updating the rules regarding the usage of BPA by
extending the prohibition of BPA to include in the production of papers, on
February 2018. Therefore, it is essential to establish the trace level BPA
detectors in paper samples. In this report, the synthesis of novel ZnO
nanoclusters wrapped with reduced graphene oxide (ZnO NCs/rGO) and its
application towards the selective electrocatalytic detection of BPA are
described. Initially, ZnO NCs/rGO is synthesized by the one-step hydrothermal
approach, and various characterizations explain the compound's compositions and
structure. The significance of ZnO NCs/rGO together with good electrocatalytic
properties leads this material to the platform for electrochemical sensor.
Finally, ZnO NCs/rGO was fabricated and validated as an effective sensor for the
sensitive detection of BPA. The demonstrated sensor revealed excellent detection
of BPA with the very low detection limit (2.1 nM), and also it offered good
analytical parameters with more extensive linear range and higher sensitivity.
Likewise, the sensor annexes good durability, reproducibility, and selectivity
towards the determination of BPA. Due to the nourishing capacity of the prepared
ZnO NCs/rGO, it is employed for the detection of BPA in tissue paper samples.
PMID- 29940509
TI - Noradrenaline induces peripheral antinociception by endogenous opioid release.
AB - BACKGROUND: The aim of this study was to investigate this involvement in not
inflammatory model of pain and which opioid receptor subtype mediates
noradrenaline-induced peripheral antinociception. Noradrenaline is involved in
the intrinsic control of pain-inducing pro-nociceptive effects in the primary
afferent nociceptors. However, inflammation can induce various plastic changes in
the central and peripheral noradrenergic system that, upon interaction with the
immune system, may contribute, in part, to peripheral antinociception. METHODS:
Hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2,
2MUg) into the plantar surface of the right hind paw and the paw pressure test to
evaluated the hyperalgesia was used. Noradrenaline (NA) was administered locally
into right hind paw of Wistar rat (160-200g) alone and after either agents,
alpha2-adrenoceptor antagonist yohimbine, alpha1-adrenoceptor antagonist
prazosin, beta-adrenoceptor antagonist propranolol, MU-opioid antagonist
clocinnamox, delta-opioid antagonist naltrindole and kappa-opioid antagonist nor
binaltorfimina. In addition, the enkephalinase inhibitor bestatin was
administered prior to NA low dose. RESULTS: Intraplantar injection of NA induced
peripheral antinociception against hyperalgesia induced by PGE2. This effect was
reversed, in dose dependent manner, by intraplantar injection of yohimbine,
prazosin, propranolol, clocinnamox and naltrindole. However, injection of nor
binaltorfimina did not alter antinociception of NA after PGE2 hyperalgesia.
Bestatin intensified the antinociceptive effects of low-dose of NA. CONCLUSION:
Besides the alpha2-adrenoceptor, the present data provide evidence that, in
absence of inflammation, NA activating alpha1 and beta-adrenoceptor induce
endogenous opioid release to produce peripheral antinociceptive effect by MU and
delta opioid receptors.
PMID- 29940511
TI - Hypertensive and toxicological health risk among women exposed to biomass smoke:
A rural Indian scenario.
AB - This study shows that exposure to air pollutants from indoor cooking fuel
combustion may be associated with elevated Diastolic Blood Pressure (DBP),
Systolic Blood Pressure (SBP), Heart rate and Body mass index (BMI) in rural
women of India. 60 premenopausal women (using solely agriculture residues, wood,
dung, straw, leaf) and 30 women (solely using clean fuel, LPG) were recruited for
this study. An ethically approved questionnaire was used in the study and health
parameters were measured by standard instruments. Eight pollutants were measured
by calibrated instruments, applied both in the living room as well as kitchens of
test-subjects. The Test-subjects were divided into two groups, LPG users, and
biomass users, and the toxicological risk was assessed by measurement of PM2.5
levels in the given indoor environments. The concentrations of all the pollutants
were significantly (p < 0.001) higher in biomass users than in LPG using
households, except in the case of O3 (p < 0.403) at the time of cooking. Results
highlighted that DBP (p < 0.070), SBP (p < 0.143), Heart rate (p < 0.002) and BMI
(p < 0.052) were varied in the two fuel user groups. In the case of biomass fuel
user toxicological risk was higher (5.21) than LPG users (0.69). Moreover,
Symptoms like asthma (25%), cough (76.67%), dizziness (36.67%), eye irritation
(88.33%), and shortness of breath (43.33%) were highly prevalent among biomass
users than in LPG users. The study highlighted that Biomass using women are more
prone to cardiovascular disease and policies should be formulated for their
sustainable health.
PMID- 29940512
TI - Toxicity of six insecticides to predatory mite Amblyseius cucumeris (Oudemans)
(Acari: Phytoseiidae) in- and off-field.
AB - Amblyseius cucumeris (Oudemans) is a beneficial non-target arthropod (NTA) and a
key predator of tetranychid mites in integrated pest management (IPM) programs
across China. Evaluating the toxic effects of insecticides on such predatory
mites is essential for the success and development of IPM. We tested six
insecticides to determine the risk of neonicotinoid insecticide toxicity to
predatory mites, using the 'open glass plate method' and adult female A.
cucumeris in a "worst case laboratory exposure" scenario. A 48-h toxicity test
was performed using the hazard quotient (HQ) approach to evaluate the risk of
each insecticide. The LR50 values (application rate that caused 50% mortality) of
acetamiprid, thiamethoxam, imidacloprid, and dinotefuran were 76.4, 104.5, 84.9,
and 224.6 g active ingredient (a.i.) ha-1, respectively, with in-field HQ values
of 0.40, 1.28, 0.49, and 0.82, respectively. The HQ values were lower than the
trigger value of 2, and were consistent with off-field values. The risks of the
four neonicotinoid insecticides to adult female A. cucumeris were acceptable in
two exposure scenarios in field and off field. The 48-h LR50 values for
bifenthrin and malathion were 0.008 and 0.062 g. a.i. ha-1, respectively, which
were much lower than the recommended field application rates. The HQ values were
much higher than the trigger values for both in- and off-field, indicating that
the risks of these two insecticides were unacceptable. Bifenthrin and malathion
posed an extremely high risk to the test species, and their use should be
restricted to reduce risks to the field with augmentative releases of A.
cucumeris.
PMID- 29940513
TI - Osteotoxicity of 3-methylcholanthrene in fish.
AB - Many chemicals produced by human activities end up in the aquatic ecosystem
causing adverse developmental and reproductive effects in aquatic organisms.
There is evidence that some anthropogenic chemicals disturb bone formation and
skeletal development but the lack of suitable in vitro and in vivo systems for
testing has hindered the identification of underlying mechanisms of
osteotoxicity. Several fish systems - an in vitro cell system to study
extracellular matrix mineralization and in vivo systems to evaluate bone
formation and skeletogenesis - were combined to collect data on the osteotoxic
activity of 3-methylcholanthrene (3-MC), a polycyclic aromatic hydrocarbon. Anti
mineralogenic effects, increased incidence of skeletal deformities and reduced
bone formation and regeneration were observed in zebrafish upon exposure to 3-MC.
Pathway reporter array revealed the role of the aryl hydrocarbon receptor 2
(Ahr2) in the mechanisms underlying 3-MC osteotoxicity in mineralogenic cell
lines. Analysis of gene expression in zebrafish larvae confirmed the role of Ahr2
in the signaling of 3-MC toxicity. It also indicated a possible complementary
action of the pregnane X receptor (Pxr) in the regulation of genes involved in
bone cell activity and differentiation but also in xenobiotic metabolism. Data
reported here demonstrated the osteotoxicity of 3-MC but also confirmed the
suitability of fish systems to gain insights into the toxic mechanisms of
compounds affecting skeletal and bone formation.
PMID- 29940514
TI - Combination of phenobarbital with phenytoin and pregabalin produces synergy in
the mouse tonic-clonic seizure model: An isobolographic analysis.
AB - AIMS: Despite many antiepileptic drugs (AEDs) are available to treat epilepsy,
there is still about 30% of epilepsy patients inadequately treated with these
AEDs. For these patients, polytherapy with two or three AEDs to fully control
their seizure attacks is recommended. Unfortunately, polytherapy is always
associated with drug interactions, whose nature may be beneficial, neutral or
unfavorable. To determine a type of interaction for the combination of three AEDs
(i.e., phenobarbital [PB], phenytoin [PHT] and pregabalin [PGB]) at the fixed
ratio of 1:1:1, we used a model of tonic-clonic seizures in male albino Swiss
mice. MATERIALS AND METHOD: Tonic-clonic seizures in mice were evoked by a
current (sine-wave, 25 mA, 500 V, 0.2 s stimulus duration) delivered via
auricular electrodes. The anticonvulsant effects of the three-drug combination
(PB, PHT and PGB) in terms of suppression of tonic-clonic seizures in mice were
assessed with type I isobolographic analysis. Potential acute side effects for
the mixture of PB, PHT and PGB along with total brain concentrations of the AEDs
were determined to confirm pharmacodynamic nature of observed interaction.
RESULTS: The three-drug combination of PB, PHT and PGB (at the fixed-ratio of
1:1:1) exerted synergistic interaction (at P < 0.01) in the mouse model of tonic
clonic seizures. The combination of PB, PHT and PGB did not produce any side
effects in experimental animals, when measuring long-term memory, muscular
strength and motor coordination. The measurement of total brain concentrations of
PB, PHT and PGB was conducted to confirm that none of the three AEDs
significantly influenced total brain concentrations (pharmacokinetic profiles) of
the other co-administered AEDs in mice. CONCLUSIONS: The synergistic
pharmacodynamic interaction for the combination of PB, PHT and PGB observed in
this preclinical study can be translated into clinical settings and this
favorable AED combination is worthy of being recommended to some patients with
refractory epilepsy.
PMID- 29940515
TI - Participatory environmental governance of infrastructure projects affecting
reindeer husbandry in the Arctic.
AB - Several infrastructure projects are under development or already operational
across the Arctic region. Often the deployment of such projects creates benefits
at the national, regional, or global scales. However, local communities can
experience negative impacts due to the requirements for extensive land areas,
which cause pressure on traditional land use. Public participation in
environmental planning such as Environmental Impact Assessment (EIA) enables
local communities to provide feedback on the environmental, social, and economic
challenges of infrastructure projects. Ideally, participation can improve the
means of social learning for all involved parties and help to co-develop
sustainable solutions. The subject of our research is reindeer herders'
participation in EIA procedures of mines and wind farms in Finland because these
types of projects affect reindeer husbandry. We study empirically how
stakeholders involved in the EIAs perceive the participation of reindeer herders
in the planning and implementation of infrastructure projects, and how these
differ from the perceptions of the reindeer herders who are affected by the
infrastructure projects. Our qualitative data is based on in-depth semi
structured interviews (N = 31) with members of the industry sector, consultants,
governmental authorities, and representatives of local communities; in this
study, the reindeer herders. The results show that herders' level of
participation in the EIAs and the benefits and challenges of participation are
perceived differently. Furthermore, the regulatory framework does not adequately
ensure that the developer carries social and environmental responsibilities
throughout the infrastructure project's lifetime, and that regular communication
with herders will also be maintained after the EIAs. Herders' expertise should be
used throughout the project lifetime. For example, more attention should be paid
to both negotiating possible options for compensation and monitoring mechanisms
when the infrastructure projects are pre-screened for the EIAs, as well as to co
designing the different project alternatives with herders for the EIAs.
PMID- 29940516
TI - Effects of vegetation management on plant diversity in traditional irrigation
systems.
AB - Acequias are historical community-operated water channels used for irrigating of
traditional farming areas (vegas). They have been traditionally managed by local
inhabitants, either by clearing weeds or by burning them in winter, in order to
keep the channels clean of vegetation, thus avoiding their clogging. The impact
of these cultural practices on vegetation has not still been studied. The aim of
this paper is to show how traditional management influences floristic
biodiversity in a traditional acequia in the vega of Granada (SE Spain). The
acequia was treated following the traditional methodology used by farmers, being
divided into areas that were burned, cleared, or left unchanged as control
(January 2016). Afterwards, we collected soil samples and analyzed them in the
lab to determine the treatment effects on soil properties. Vegetation was
monitored in late spring 2016 in order to detect differences between treatments.
Traditional management increased plant diversity, this effect being much more
patent for the burning than for clearing treatment. Soil analyses revealed only
slight differences in pH and CaCO3 content, higher for the burning treatment. The
increase in plant diversity found in areas treated by traditional management was
due mainly to the reduction of competition, which promoted the emergence or
increase of populations of non-dominant species. The results indicated that
traditional management not only offers advantages to the farmers but also
promotes plant diversity and ecosystem services.
PMID- 29940518
TI - Deciphering Drosophila female innate behaviors.
AB - Innate responses are often sexually dimorphic. Studies of female specific
behaviors have remained niche, but the focus is changing as illustrated by the
recent progress in understanding the female courtship responses and egg-laying
decisions. In this review, we will cover our current knowledge about female
behaviors in these two specific contexts. Recent studies elucidate on how females
process the courtship song. They also show that egg-laying decisions are
extremely complex, requiring the assessment of food, microbial, predator and
social cues. Study of female responses will improve our understanding of how a
nervous system processes different challenges.
PMID- 29940517
TI - Comparison of acetabular and femoral morphologies on hip, pelvic, and lumbar
radiographs.
AB - PURPOSE: To evaluate the reliability of the parameters for acetabular/femoral
pathomorphologies in L-spine and hip radiographs compared to pelvic radiographs.
METHODS: A retrospective review of L-spine, hip, and pelvic radiographs from 101
patients was performed. Three radiologists independently measured five parameters
(acetabular roof angle of Tonnis [Tonnis angle], center-edge-angle of Wiberg
[CEA], femoral head extrusion index [FHEI], cross-over sign, pistol-grip
deformity) in each radiograph. RESULTS: No significant differences were
identified (p >= 0.07) except Tonnis angles and FHEIs from the L-spine
radiographs. Inter-radiograph/inter-reader ICCs were excellent or good.
CONCLUSION: Pathomorphology-related measurements in L-spine radiographs can also
be used as alternatives to those in pelvic or hip radiographs. If L-spine
radiographs are already available, additional pelvic or hip radiographs may be
unnecessary, thus reducing patients' overall radiation exposure.
PMID- 29940519
TI - Prospective association between combined healthy lifestyles and risk of
depressive symptoms in the French NutriNet-Sante cohort.
AB - BACKGROUND: Several modifiable lifestyle indicators, including diet, smoking,
alcohol consumption, weight and physical activity have been associated with
depression; however, their combined effect has been less studied. The aim of this
study was to calculate a Healthy Lifestyle Index (HLI) composed of the 5 above
mentioned indicators and investigate its association with incident depressive
symptoms. METHODS: The study sample consisted of 25,837 participants from the
NutriNet-Sante study, initially free of depressive symptoms. The HLI was computed
by assigning 1 point to each lifestyle indicator namely healthy diet, healthy
weight, moderate or high physical activity, never smoking and low alcohol
consumption. Depressive symptoms were measured using the Center for Epidemiologic
Studies Depression Scale (CES-D). Hazard Ratios were estimated using Cox
proportional hazards models and population attributable risks (PAR) were
calculated. RESULTS: A total of 2112 incident cases of depressive symptoms were
identified over a mean follow-up of 5 years. After accounting for a wide range of
potential confounders, a 1-point increase in the HLI was associated with a 10%
(95% CI 6%; 13%) reduction in the risk of depressive symptoms. The estimated PAR
representing the proportion of cases that are attributable to non-adherence to
specific healthy lifestyle indicators were 8% for healthy diet, 5% for healthy
weight, 5% for non-smoking and 14% for the non-adherence to a combination of
healthy diet, healthy weight and non-smoking. LIMITATIONS: Some unmeasured
factors related to both depression and lifestyle indicators, such as family
history of depressive disorder, stressful life events, and sleep disorders might
have led to potential residual confounding. CONCLUSIONS: Modifying unhealthy
lifestyles, especially diet, weight and smoking, is a potential target of major
interest in the prevention of depressive symptoms in adults.
PMID- 29940520
TI - Prior suicide attempts predict worse clinical and functional outcomes in young
people attending a mental health service.
AB - BACKGROUND: Mental disorders and suicidal thoughts and behaviours are common in
help-seeking youth. Few studies report the longitudinal associations between
these phenomena and clinical and functional outcomes. This study examined whether
prior suicide attempts predict poorer outcomes in mental health service
attendees. METHODS: Clinical and functional data from 1143 individuals (aged 12
30) attending a primary care-based mental health service in Australia were
collected over 3-60 months (median = 21 months). Odds ratios (OR) with 95%
confidence intervals for the effect of a prior suicide attempt on follow-up
outcomes were estimated (adjusted for confounders). RESULTS: Prior suicide
attempts were common (n = 164; 14%) and prospectively associated with suicidal
thoughts (OR = 1.71), suicide attempts (OR = 2.59), self-harm (OR = 1.71), an
increased likelihood of being diagnosed with bipolar disorder (OR = 2.99), and
the onset of an alcohol/substance use disorder (OR = 2.87). Over the course of
care, no suicide attempts were reported in 1052 (92%) individuals, but 25 (2%)
had recurrent attempts, and 66 (6%) had new onset of an attempt. New onset was
associated with being female and previous suicidal ideation or self-harm;
recurrent attempts were associated with being older and comorbid
alcohol/substance use disorder. LIMITATIONS: The cohort includes only individuals
who remained in clinical contact, and the consistency of their documentation
varied (across clinicians and over time). CONCLUSIONS: Young people with prior
suicide attempts are vulnerable to ongoing suicidal behaviours, and poorer
clinical and functional outcomes. More intensive management strategies may be
needed to directly address these behaviours and the long-term risks they confer.
These behaviours also emerge over the course of care among those with no previous
history, which has important implications for active service-level strategies
that target these behaviours for all of those who present to such services.
PMID- 29940521
TI - Efficacy of extended clinical management, group CBT, and group plus individual
CBT for major depression: Results of a two-year follow-up study.
AB - OBJECTIVE: Cognitive therapy has gained prominence in the treatment of major
depression, however, little is known about its long-term benefits when delivered
during inpatient treatment or combined with outpatient treatment with severely
ill inpatients (HAM-D > 20). METHOD: To evaluate this question, we conducted a
randomized controlled trial investigating the efficacy of extended clinical
management (E-CM), psychoeducational cognitive behavioural group therapy (PCBT-G)
or PCBT-G and 16 outpatient individual treatment sessions (PCBT-G+I). All
patients were treated with pharmacotherapy. 177 inpatients with DSM-IV major
depression were randomized either to E-CM or PCBT-G or PCBT-G+I. Outcome measures
were collected in the hospital at pre- and posttreatment and following discharge
into the community every six months for two years. We compared the study groups
on symptom changes, psychosocial functioning, knowledge about depression and
rehospitalization. RESULTS: All three treatment interventions are equally
effective at reducing depressive symptoms and increasing psychosocial functioning
at posttreatment. There was significant group by time interaction for knowledge
about depression in favor of PCBT-G and PCBT-G+I over E-CM. We did not find
significantly lower rehospitalisation rates at the two-year follow-up for PCBT
G+I compared to E-CM, however, comparing PCBT-G to E-CM. CONCLUSIONS: We conclude
that with cognitive psychoeducational group therapy a successful, in the long
term other interventions superior psychological intervention for major depression
is available as gains were sustained for two years following discharge from the
hospital. More research is needed to evaluate the long-term impact of group
treatment starting in inpatient treatment.
PMID- 29940522
TI - Assessing the social dimension of frailty in old age: A systematic review.
AB - INTRODUCTION: Different concepts of frailty have resulted in different assessment
tools covering distinct dimensions. Despite the growing recognition that there is
an association between frailty and social factors, there's a lack of clarity on
what is being assessed in terms of "social aspects" of frailty. OBJECTIVE: This
paper provides a review of frailty assessment instruments (screening tools and
severity measures) with a special focus on their social components. METHODS:
Systematic review of studies published in English between 2001 and March 2018 in
the PubMed database using a combination of MeSH Terms and logical operators
through inclusion and exclusion criteria. RESULTS: A total of 27 assessment tools
including at least one social question were identified. Three instruments focuses
exclusively on social frailty, whereas the weight of social dimensions in the
other instruments ranges between 5% and 43%. Social activities, social support,
social network, loneliness and living alone were the social concepts most
represented by the social components of the various frailty instruments.
CONCLUSION: Social components of frailty vary from instrument to instrument and
cover the concepts of social isolation, loneliness, social network, social
support and social participation.
PMID- 29940523
TI - Synchronized electromechanical integration recording of cardiomyocytes.
AB - Cardiac issues are always one of major health problems that attract wide
attention by the public. It is urgent to explore a preclinical strategy to
efficiently prevent the life-threatening arrhythmias by precisely assessing the
cardiac excitation-contraction behavior. Conventional label-free asynchronous
strategies are difficult to synchronously record and precisely match the
excitation and contraction signals in vitro, while label-based strategies
generally present pharmacological adverse effects and phototoxicity that
significantly interfere the natural excitation and contraction signals. Both
types of strategies preclude to exactly understand how cardiac excitation
contraction coupling changes in quantitative and coherent detail when
dysfunctions occur. Here, we show a label-free synchronized electromechanical
integration detection strategy that can synchronously monitor electrical and
mechanical signals of cardiomyocytes over a long period of time by an integrated
microelectrode-interdigitated electrode (ME-IDE). ME-IDE can detect subtle
changes in electromechanical integration signals induced by drugs that target
excitation-contraction coupling. Moreover, electromechanical integration delay is
explored to specifically recognize the sodium channel inhibition. Furthermore,
biomimetic electronic pacemaker function provides an alternative way to
efficiently assess the drug-induced arrhythmia using refractory period of
cardiomyocytes.
PMID- 29940524
TI - Androgen receptor in triple negative breast cancer: A potential target for the
targetless subtype.
AB - Triple negative breast cancer (TNBC) represents the 15-20% of all breast cancers
(BC) and is characterized by a very aggressive behavior. Recent data suggest that
TNBC is not a single disease, but it is rather an umbrella for different ontology
profiles such as basal like 1 and 2, mesenchymal, and the luminal androgen
receptor (LAR). The LAR subtype is characterized by the expression of the
Androgen Receptor (AR) and its downstream effects. Notwithstanding the role of
the AR in several signaling pathways, its impact on a biological and clinical
standpoint is still controversial. The LAR subtype has been associated with
better prognosis, less chemotherapy responsiveness and lower pathologic complete
response after neoadjuvant treatment. Clinical evidence suggests a role for anti
androgen therapies such as bicalutamide, enzalutamide and abiraterone, offering
an interesting chemo-free alternative for chemo-unresponsive patients, and
therefore potentially shifting current treatment strategies.
PMID- 29940525
TI - Fifty years of rhabdomyosarcoma studies on both sides of the pond and lessons
learned.
AB - We review and summarize the highlights of almost five decades of cooperative
group trials in rhabdomyosarcoma on both sides of the Atlantic, concentrating on
chemotherapy regimens, what has been learned, and where remaining challenges are.
The most important achievements have been to decrease or omit the dose of
alkylator therapy for many patients, to clarify after much controversy that
doxorubicin does not improve the outcome of patients even in the highest risk
groups, and to show that high dose chemotherapy and stem cell rescue do not
improve the outcome of the highest risk patients. In North America,
vincristine/actinomycin/cyclophosphamide (VAC) remains an important part of
therapy, whereas in Europe the alkylating agent of choice is ifosfamide. The
highest risk patients, namely those with the poorest prognostic score, have had
no improvement in outcome since the first cooperative group trial in 1972 and
remain the greatest challenge. Philosophical differences between European and
North American strategies still revolve somewhat around the total burden of
therapy received, that is should certain groups of patients be spared aggressive
local control in order to reduce late effects, recognizing that it is not
possible to identify priori the children that can be cured with this approach
exposing the whole population to a higher risk of relapse. Collaboration and
joining resources may help answer some difficult questions.
PMID- 29940526
TI - Determination of correction factors in beta radiation beams using Monte Carlo
method.
AB - The absorbed dose rate is the main characterization quantity for beta radiation.
The extrapolation chamber is considered the primary standard instrument. To
determine absorbed dose rates in beta radiation beams, it is necessary to
establish several correction factors. In this work, the correction factors for
the backscatter due to the collecting electrode and to the guard ring, and the
correction factor for Bremsstrahlung in beta secondary standard radiation beams
are presented. For this purpose, the Monte Carlo method was applied. The results
obtained are considered acceptable, and they agree within the uncertainties. The
differences between the backscatter factors determined by the Monte Carlo method
and those of the ISO standard were 0.6%, 0.9% and 2.04% for 90Sr/90Y, 85Kr and
147Pm sources respectively. The differences between the Bremsstrahlung factors
determined by the Monte Carlo method and those of the ISO were 0.25%, 0.6% and 1%
for 90Sr/90Y, 85Kr and 147Pm sources respectively.
PMID- 29940527
TI - Dynamic material decomposition method for MeV dual-energy X-ray CT.
AB - A decomposition model with an iterative solving framework is proposed for use in
MeV dual energy computed tomography (DECT). The decomposition model can deal with
a broad range of materials and better matches the physics of MeV photons. The
proposed iterative solving framework is based on the conventional projection
domain decomposition method, and verified by numerical experiments and
experiments. It is shown that images reconstructed with the proposed method have
less artifacts and provide more accurate estimates of the atomic number of
materials than the conventional projection-domain decomposition method.
PMID- 29940528
TI - Magnetic dithiocarbamate functionalized reduced graphene oxide for the removal of
Cu(II), Cd(II), Pb(II), and Hg(II) ions from aqueous solution: Synthesis,
adsorption, and regeneration.
AB - In this study, dithiocarbamate(DTC)-modified magnetic reduce graphene oxide (rGO
PDTC/Fe3O4) was synthesized for the removal of heavy metal ions (Cu(II), Cd(II),
Pb(II), and Hg(II)) in synthetic waste water. The rGO-PDTC/Fe3O4 nanocomposite
was prepared via a novel synthesis route that includes GO bromination,
nucleophilic substitution of polyethylenimine (PEI), the reaction with carbon
disulphide (CS2) and Fe3O4 nanoparticle loading. The prepared rGO-PDTC/Fe3O4
nanocomposite was characterised by XPS, FTIR, TEM and XRD, suggesting that DTC
functional groups were chemically bonded to rGO surfaces. N2 adsorption
desorption results revealed that rGO-PDTC/Fe3O4 nanocomposite exhibited high BET
surface area (194.8 m2/g) and large pore volume (0.33 cm3/g) which are crucial to
the function of adsorbent. Adsorption experiments showed that rGO-PDTC/Fe3O4
nanocomposite is an excellent adsorbent for heavy metal removal, which exhibits
large adsorption capacities, fast kinetics and solid-liquid separation. The
pseudo-second-order kinetic model and Langmuir adsorption model were used to
unveil the adsorption mechanisms. The maximum adsorption capacities of the
Langmuir model were 113.64, 116.28, 147.06, and 181.82 mg/g for Cu(II), Cd(II),
Pb(II), and Hg(II) ions, respectively. After adsorption and desorption process,
the spent rGO-PDTC/Fe3O4 nanocomposite was easily regenerated via one-step
organic reaction. The regenerated rGO-PDTC/Fe3O4 composite exhibited good
adsorption capacities for different metals in five adsorption-desorption
regeneration cycles.
PMID- 29940529
TI - Utilizing recycled LiFePO4 from batteries in combination with B@C3N4 and CuFe2O4
as sustainable nano-junctions for high performance degradation of atenolol.
AB - In this report recycled LiFePO4 (LFP) from exhaust batteries was utilized to form
B@C3N4/LiFePO4/CuFe2O4 (BLC) nano-junction as a visible active photocatalyst. The
junction synthesized by two routes: Using as extracted LFP and forming LFP by
extracted FePO4 and Li2CO3 via in-situ deposition method. The two ternary
junctions BLC and BLC (E) (utilizing as extracted LFP) were utilized for visible
and solar powered degradation of beta-blocker drug Atenolol (ATL). Varying the
loading of CuFe2O4 (CF) which possesses lowest band gap, BLC (10%), BLC-3 (30%),
BLC-5 (50%) and BLC-E (30% CF and as extracted LFP) were produced with BLC-3
exhibiting remarkable activity. The optical band gaps of BLC-3 (2.40 eV) and BLC
(E) (2.46 eV) and photocurrent responses reveal high visible absorption and
highly diminished recombination. 99.5% and 85.3% of ATL (20 mg L-1) could be
degraded by BLC-3 and BLC (E) (0.3 g L-1) respectively in 60 min of exposure to
Xe lamp and retaining of high activity in natural sunlight. Band-junction
analysis, effect of scavengers and effect on teraphthalic acid and nitroblue
tetrazolium reveal O2- and OH radicals as active species and mineralization was
confirmed by liquid chromatography-mass spectrometer (LC-MS). Cyto-toxicity
studies on human peripheral blood cells and effect on growth of Pseudomonas
aeruginosa confirm the complete mineralization. The BLC photocatalyst is a
promising multi-functional catalyst utilizing LFP (rarely used as photocatalyst)
for treatment of pharmaceutical waste water and other environmental applications.
PMID- 29940530
TI - Application of zinc-aluminium layered double hydroxides for adsorptive removal of
phosphate and sulfate: Equilibrium, kinetic and thermodynamic.
AB - In this study, a series of layered double hydroxide (ZxAy LDH) material was
synthesized with different molar ratios and calcination temperatures to remove
phosphate and sulfate ions from synthetic solution. ZxAy LDH was characterized by
XRD, FTIR, BET and SEM analysis. The highest removal was obtained by Z3A200 LDH
that is LDH with a Zn-Al molar ratio of 3 and calcined at 200 degrees C. The
leaching of Zn and Al was more under highly acidic pH compared to pH 5 and 8.
Adsorption isotherms data had a good fit with Langmuir model and maximum
adsorption under optimum conditions led to 2.6-2.72 and 1.02-1.31 mmol/g for
phosphate and sulfate, respectively. Kinetic studies have been performed by
applying reaction based models and diffusion-based models, which indicated the
chemisorption interaction for Z3A200 by a controlling step of the macro-pore and
micro-pore diffusion for phosphate and sulfate adsorption process onto Z3A200,
respectively. Thermodynamic studies showed that adsorption process onto Z3A200
was endothermic and spontaneous. Thus, phosphate and sulfate adsorption by using
optimized Zn-Al LDH appears to be a promising adsorbent for their removal.
PMID- 29940531
TI - Metal removal from soil leachates using DTPA-functionalised maghemite
nanoparticles, a potential soil washing technology.
AB - There is significant current interest in the application of magnetic (magnetite
or maghemite) nanoparticles functionalised with chelating agents for the
environmental remediation of metal contaminated waters and solutions. Whilst
there is a body of knowledge about the potential remediation efficacy of such
engineered nanoparticles from studies involving synthetic solutions of single
metals, there is relatively little data involving mixed-metal solutions and
virtually no studies about nanoparticle performance in chemically complex
environmental solutions representing those to which a scaled-up nanoremediation
process might eventually be applied. Therefore, we investigated the ability of
diethylenetriaminepentaacetic acid (DTPA)-functionalised, silica-coated maghemite
nanoparticles to extract potentially toxic (Cd, Co, Cu) and "non-toxic" (Ca, Mg)
metals from solution (initial [metal] = 10 mg L-1; pH range: 2-8) and to extract
a wider range of elements (As, Ca, Cd, Co, Cr, Cu, Mg, Na, Pb, Zn) from leachate
obtained from 10 different contaminated soils with variable initial pH, (semi
)metal and dissolved organic carbon (DOC) concentrations. The functionalised
nanoparticles could extract the potentially toxic metals with high efficiency (in
general >70%) from single metal solutions and with efficiencies that were either
unaffected or reduced from the soil leachates. Kd values remained high (>500 L kg
1), even for the soil leachate extractions. Our findings show that DOC and
relatively high concentrations of non-toxic elements do not necessarily reduce
the efficiency of metal contaminant removal by DTPA-functionalised magnetic
nanoparticles and thus demonstrate the remediation potential of such particles
when added to chemically complex soil-derived contaminated solutions.
PMID- 29940532
TI - Effects of carrier on the transport and DDT removal performance of nano
zerovalent iron in packed sands.
AB - The delivery of nano-zerovalent iron (nZVI) as a remediation agent to targeted
areas in soil was studied using different carriers. Among water, surfactant
solution, and surfactant foam, the nZVI transport and carrying abilities followed
the order of surfactant foam > surfactant solution > water. The nZVI migration
was also facilitated by increased soil particle size and high surfactant
concentration. Batch experiments probed the remediation of
dichlorodiphenyltrichloroethane (DDT)-contaminated sand under different
conditions. Compared to surfactant solution, the use of foam as a carrier
achieved much higher DDT removal efficiencies for both coarse (foam/solution:
99/69%) and fine (foam/solution: 60/26%) sands. Additionally, the DDT removal
efficiency was strongly influenced by surfactant concentration: foams generated
using 1 and 5 g L-1 sodium lauryl ether sulfate (SLES) solutions reached the
respective efficiencies of 44% and 75% under identical experimental conditions.
However, the nature of the surfactant did not significantly affect the total
removal efficiency of DDT. Solubilization, increased sweep efficiency, and
reduction by nZVI were identified as factors affecting the DDT removal
efficiency, and all three of them were involved when foam-nZVI was used as the
flushing fluid.
PMID- 29940533
TI - Analysis of pesticides in surface water, stemflow, and throughfall in an
agricultural area in South Georgia, USA.
AB - To study spray drift contributions to non-targeted habitats, pesticide
concentrations in stemflow (water flowing down the trunk of a tree during a rain
event), throughfall (water from tree canopy only), and surface water in an
agriculturally impacted wetland area near Tifton, Georgia, USA were measured
(2015-2016). Agricultural fields and sampling locations were on the University of
Georgia's Gibbs Research Farm, Tifton, GA. Samples were screened for more than
160 pesticides, and cumulatively, 32 different pesticides were detected across
matrices. Data indicate that herbicides and fungicides were present in all types
of environmental samples analyzed while insecticides were only detected in
surface water samples. The highest pesticide concentration observed was 10.50
MUg/L of metolachlor in an August 2015 surface water sample. Metolachlor,
tebuconazole, and fipronil were the most frequently detected herbicide,
fungicide, and insecticide, respectively, regardless of sample origin. The most
frequently detected pesticide in surface water and stemflow samples was
metolachlor (0.09-10.5 MUg/L), however, the most commonly detected pesticide in
throughfall samples was biphenyl (0.02-0.07 MUg/L). These data help determine the
importance of indirect chemical exposures to non-targeted habitats by assessing
inputs from stemflow and throughfall into surface waters.
PMID- 29940534
TI - Bisphenol A and its analogs bisphenol B, bisphenol F, and bisphenol S:
Comparative in vitro and in vivo studies on the sperms and testicular tissues of
rats.
AB - Bisphenol A (BPA) is used as the main component of many consumer products such as
infant's feeding bottles, coatings of beverages, and food cans. BPA can migrate
into the environment, and it has been detected in the saliva, blood, and food.
BPA leakage from many consumer products resulted in a ban on its use in many
countries where alternatives to BPA were introduced into the market. BPA
alternatives such as bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS)
have a similar chemical structure and binding ability for estrogen receptor (ER),
which shows toxicological effects in animals. In the present study, comparative
effects of exposure to BPA and its analogs BPB, BPF, and BPS on testosterone
concentration in the rat testis were evaluated by in vitro and in vivo approaches
in which oxidative stress markers and antioxidant enzyme activities in
reproductive tissues were determined. In the in vivo study, male rats were
exposed to different concentrations of BPA and its analogs BPB, BPF, and BPS (5,
25, and 50 mg/kg/day) for 28 days. In the in vitro exposure study, antioxidant
enzyme activities and oxidative stress markers were induced in the testes,
whereas testosterone production was reduced. In the in vivo exposure study, we
observed that antioxidant enzyme activities and protein content were reduced,
whereas reactive oxygen species and lipid profile were increased in the treated
groups compared to the control group. The present comparative study on BPA and
its analogs, namely, BPB, BPF, and BPS suggests the toxic effect of these
chemicals on the testes and spermatogenesis, and we also observed that these
chemicals induce oxidative stress in the reproductive tissues of male rats.
PMID- 29940535
TI - Configural face perception in childhood and adolescence: An individual
differences approach.
AB - Cognitive experimental and neuroscientific research in adults indicates that an
important property of face perception is its specificity and reliance on
configural processing. In addition, individual differences in face perception
between adults cannot be entirely explained through general cognitive functioning
and object cognition. Although recent years have witnessed growing interest in
the development of face perception through childhood and adolescence, as yet,
little is known about individual differences in configural face perception in
this period of life, and whether these differences are face-specific. Here, we
addressed these questions in a large sample (N = 338) drawn continuously from age
six to 21. We applied a face composite task and a spatial manipulation task
including stimulus inversion. Immediate and delayed face memory were assessed as
covariates of configural face perception. Content specificity in configural face
perception was tested by analogous tasks with houses as stimuli. In addition, we
measured working memory and fluid intelligence. Our results show that there are
large individual differences in configural face perception across the entire age
range from six to 21 years. Supporting theories of early maturation, configural
face perception was almost adult-like already at age six. Individual differences
in configural face perception were related with immediate and delayed face memory
and fluid intelligence across the whole age range. In sum, we provide novel
evidence on large individual differences in configural face and object perception
already in middle childhood, complementing findings from aging studies and
providing new perspectives for further research.
PMID- 29940537
TI - CPT1A regulates breast cancer-associated lymphangiogenesis via VEGF signaling.
AB - BACKGROUND: Lymphangiogenesis is critical for metastasis of a variety of cancers,
including breast cancer. CPT1A (carnitine palmitoyltransferase 1a) has been
reported to play a critical role in breast cancer progress. However, the
molecular mechanism remains elusive. METHODS: In order to investigate the role of
CPT1A in HDLEC cells, short hairpin RNA approach was utilized to knock down the
CPT1A gene expression. We employed transwell and lymphatic vessel formation assay
to examine invasion and lymphangiogenesis of HDLEC (Human dermal lymphatic
endothelial cells). RT-qPCR and westernblot analyses were used to determine genes
expression in HDLEC and breast cancer cells. Finally, we determined the relative
rate of acetyl-CoA/CoA in shNC and shCPT1A HDLEC cells by LC-MS approach.
RESULTS: Knockdown of CPT1A in breast cancer cells (MCF-7 and MDA-MB-231)
abolished invasion and lymphangiogenesis of HDLEC cells. Mechanistically, CPT1A
depletion suppressed the expression of VEGF-C and VEGF-D in MCF-7 and MDA-MB-231
cells. Interestingly, CPT1A knockdown in HDLEC cells exhibited attenuated
expression of lymphangiogenic markers (podoplanin, VEGFR-3, VEGF-C, VEGF-D and
PROX-1). Consistently, CPT1A -null HDLEC cells displayed compromised invasion and
lymphangiogenesis compared with negative control. Further investigation revealed
that CPT1A regulated VEGFR3 via acetyl-CoA mediated H3K9ac, which could be
abrogated by supplement of acetate. CONCLUSIONS: In present study, we revealed
the mechanism by which CPT1A regulates breast cancer-associated invasion and
lymphangiogenesis. Our findings provide insights into CPT1A -promoted breast
tumor metastasis and provide rationale for understanding breast cancer
metastasis.
PMID- 29940536
TI - Pilot test of brief instructions to improve the self-management of general food
cravings.
AB - OBJECTIVE: To provide a preliminary investigation into the impact of brief online
acceptance-based vs. control-based techniques to self-manage food cravings in
women. METHOD: Female participants (N = 151) were randomised to 'acceptance' or
'control' groups. Measures of general food cravings (primary outcome), and
depression, anxiety and stress (secondary outcomes) were taken at baseline, two
weeks and four weeks. RESULTS: Linear mixed models showed a significant group *
time interaction, with food cravings significantly reduced in the thought-control
group compared to the acceptance group over four weeks, along with a reduction in
food consumption. Levels of depression, anxiety and stress decreased over the
course of the study, but did not differ by group. CONCLUSION: These findings
provide preliminary support for the acceptability of a minimal technique to self
manage food cravings without deleterious effects, and suggest that simple control
based techniques may be useful in non-clinical, real-world settings.
PMID- 29940538
TI - Imidazole bearing chalcones as a new class of monoamine oxidase inhibitors.
AB - In the present study, series of eleven (2E)-1-[4-(1H-imidazol-1-yl)substituted
phenyl]-3-phenylprop-2-en-1-one (IM1-IM11) derivatives were synthesized and
evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The
results indicate that (2E)-3-[4-(dimethylamino) phenyl]-1-[4-(1H-imidazol-1-yl)
phenyl] prop-2-en-1-one (IM5) is a nonselective and reversible competitive
inhibitor of MAO-A and MAO-B with IC50 values of 0.30 +/- 0.010 and 0.40 +/-
0.017 MUM, respectively ; those of (2E)-1-[4-(1H-imidazol-1-yl) phenyl]-3-(4
methylphenyl) prop-2-en-1-one (IM4) were 1.06 +/- 0.090 and 0.32 +/- 0.021 MUM,
respectively. Kinetic studies document that both IM5 and IM4 are competitive
inhibitors of MAO-A and MAO-B with Ki value of 0.11 +/- 0.0085 and 0.085 +/-
0.0064 MUM, respectively. Molecular docking studies of lead compounds further
explained the binding modes in the inhibitor binding cavity of both MAO-A and MAO
B.
PMID- 29940539
TI - [Association between body mass index and aggressiveness of papillary thyroid
carcinoma].
AB - The aim of the study was to evaluate the association of the body mass index (BMI)
with the clinical-pathological characteristics and the recurrence of papillary
thyroid carcinoma. The cohort consisted of 208 patients with papillary thyroid
carcinoma diagnosed in 2003-2014, in Buenos Aires, Argentina. The patients were
grouped according to the BMI as follows: BMI <18.5 kg/m2 (low weight); BMI >=
18.5 and < 25 kg/m2 (normal weight); BMI >= 25 and < 30 kg/m2 (overweight); BMI
>= 30 kg/m2 (obesity). Two experienced pathologists reviewed and cross-checked
all pathology specimens to confirm diagnosis, tumor characteristics and extent of
the disease. All patients were followed every 6 months for 2 years, and annually
thereafter. Recurrences were searched by using diagnostic imaging and
histological confi rmation when necessary. Regression analysis was applied to
defi ne associations of BMI with clinical, pathological, and prognosis features
of the disease. A 5-point increase in BMI was significantly associated with tumor
size (OR 1.21; 95% CI 1.1-1.5; p = 0.01) and greater extranodal extension in
cervical metastases (OR 1.11; 95% CI 1.06-1.21; p = 0.03). The analysis of
prognostic variables showed no association between increase in BMI and risk of
recurrence (HR 1.11; 95% CI 0.91-1.22). In conclusion, we found that BMI relates
directly with tumor size and extranodal extension, but not with recurrence.
PMID- 29940540
TI - [Outbreak of hantavirus pulmonary syndrome in Tucuman, Argentina].
AB - We describe an outbreak of hantavirus pulmonary syndrome in the Burruyacu
Department, Province of Tucuman. The detection in 2016 of a case of hantavirosis
affecting a 23-year-old woman, considered at that time to be the first case
occurred in that province, promoted a thorough epidemiological study. The
investigation allowed the retrospective detection of another case occurred one
month earlier in a 5-year-old child in the same Department. In both cases, the
infection was confirmed by serology (case 1 at days 4 and 7 of disease onset,
case 2 at day 4) and the viral genotype was characterized as HU39694. The
contacts of both cases were serologically negative for hantavirus. The rodents
captured in the area belonged to genus Akodon, genus Calomys and species Mus
musculus. Oligoryzomys, the known reservoir for this viral genotype, was not
found. Specific anti-hantavirus antibodies were not detected in the captured
rodents. Given that the patients had not visited hantavirus endemic areas and
their contacts were negative for hantavirus, we infer that the patients were
locally exposed to fluids of infected rodents during their usual social or
recreational outdoor activities. In conclusion, we demonstrate that hantavirus
HU39694 -a genotype until now considered to be restricted to the Central Pampas
of the country- is circulating in the North Western province of Tucuman. The
endemic area of hantavirosis is thus expanded to this province but the viral
reservoir in the area has not yet been identified.
PMID- 29940541
TI - [Motorcycles accidents: medical and economic cost at a public hospital in Buenos
Aires City].
AB - Traffic accidents cause 1.25 million deaths per year worldwide, being one of the
leading causes of death in young people, and the first cause between the ages of
15 - 29. There has been an increase in accidents in the last 10 years, one of the
reasons for this is the increase in the sales of motorcycles and its use. We
present a retrospective study about the patients who received attention at Carlos
G. Durand Hospital, (CABA, Buenos Aires, Argentina) from January 2013 to December
of 2015, with the intention of showing the medical and economic impact this
accidents cause. Of a total of 4368 incoming patients assisted, due to traffic
accidents, 67% (2926) were the result of motorcycle crashes; 18% of them required
hospitalization. Males, and lower limbs lesions were predominant.
Hospitalizations varied between 5 and 150 days, with 2.1 average surgeries per
patient. The total cost was 16 767 037$, and in 2014 it represented 17 936 US$
per patient. These results show only partially the impact these accidents
produce, because there are factors (like missing working days) that were
unaccounted for. This is why it is necessary to generate awareness and develop
more rigorous road safety and prevention policies, necessary to avoid accidents
that increase spending on preventable conditions.
PMID- 29940542
TI - [Clinical examination and the Valsalva maneuver in heart failure].
AB - Congestion in heart failure patients with reduced ejection fraction (HFrEF) is
relevant and closely linked to the clinical course. Bedside blood pressure
measurement during the Valsalva maneuver (Val) added to clinical examination may
improve the assessment of congestion when compared to NT-proBNP levels and left
atrial pressure (LAP) estimation by Doppler echocardiography, as surrogate
markers of congestion in HFrEF. A clinical examination, LAP and blood tests were
performed in 69 HFrEF ambulatory patients with left ventricular ejection fraction
<= 40% and sinus rhythm. Framingham Heart Failure Score (HFS) was used to
evaluate clinical congestion; Val was classified as normal or abnormal, NT-proBNP
was classified as low (< 1000 pg/ml) or high (>= 1000 pg/ml) and the ratio
between Doppler early mitral inflow and tissue diastolic velocity was used to
estimate LAP and was classified as low (E/e'< 15) or high (E/e' >= 15). A total
of 69 patients with HFrEF were included; 27 had a HFS >= 2 and 13 of them had
high NT-proBNP. HFS >= 2 had a 62% sensitivity, 70% specificity and a positive
likelihood ratio of 2.08 (p=0.01) to detect congestion. When Val was added to
clinical examination, the presence of a HFS >= 2 and abnormal Val showed a 100%
sensitivity, 64% specificity and a positive likelihood ratio of 2.8 (p = 0.0004).
Compared with LAP, the presence of HFS = 2 and abnormal Val had 86% sensitivity,
54% specificity and a positive likelihood ratio of 1.86 (p = 0.03). In
conclusion, an integrated clinical examination with the addition Valsalva
maneuver may improve the assessment of congestion in patients with HFrEF.
PMID- 29940543
TI - Association of body mass index with short-term outcomes after cardiac surgery:
retrospective study and meta-analysis.
AB - The relationship between higher body mass index (BMI), decreased morbidity and
mortality is known as the "obesity paradox", and has been described in cohorts of
patients with hypertension, diabetes, heart failure, coronary and peripheral
artery diseases, non-cardiac surgery, and end-stage renal disease. Here we
investigated the relationship between BMI and short-term outcomes after adult
cardiac surgery to explore the existence of an obesity paradoxical effect. A
secondary objective was to perform an updated systematic review to further
analyze the association between BMI and 30-day in-hospital mortality after
cardiac surgery. A retrospective analysis was performed from a consecutive series
of 1823 adult patients who underwent cardiac surgery, that were assigned to five
BMI groups: normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), class I
obese (30-34.9 kg/m2), class II obese (35-39.9 kg/m2), and class III obese or
morbidly obese (40-49.9 kg/m2). A systematic review search was performed
including controlled trials and observational studies identified in MEDLINE,
Embase, SCOPUS, and the Cochrane library (to the end of June 2017). In the
present series, overweight and obese patients had similar or slightly lower in
hospital mortality rates after cardiac surgery compared with normal-weight
individuals. Conversely, postoperative complication rates increased with higher
BMI levels. Most studies included in the review showed that overweight and obese
patients had at least the same mortality rate as normal-weight patients, or even
a lower death risk. Pooled-data of the meta-analysis provided evidence on the
association between higher BMI levels and a lower all-cause in-hospital mortality
rate after cardiac surgery.
PMID- 29940544
TI - [Paracoccidioidomycosis: chronicle of a neglected disease].
AB - Paracoccidioidomycosis (PCM) is among the systemic mycoses which are endemic only
in Latin America. In Argentina, the vast majority of the cases are reported at
north of latitude 34.5 degrees S. The disease is produced by thermodimorphic
fungi of the genus Paracoccidoides: P. brasiliensis (S1), P. americana (PS2), P.
restrepiensis (PS3), P. venezuelensis (PS4) y P. lutzii. The natural habitat of
members of this genus is the soil, where they produce infectious conidia. Little
is known, however, about their specific ecologic niche(s), and this knowledge gap
hampers the design of measures to control the infection. Rural male workers are
the group most at risk of developing PCM. Infection occurs by inhalation of
aerosolized conidia and may either be asymptomatic or cause mild respiratory
symptoms. In turn, this primary infection may be self-limited or progress to
severe pulmonary or disseminated disease. The disease has two clinical
presentations: (i) acute or subacute (juvenile), frequent in children,
adolescents and people with immunodeficiencies; and (ii) chronic progressive, in
adults. Active lesions often resolve into fibrotic scars which can cause
dysphagia, dysphonia, adrenal insufficiency, and intestinal obstruction. Although
efficient tools are available for diagnosis and treatment, the nonspecific nature
of PCM clinical manifestations frequently delay the diagnosis. In addition, the
poor adherence to long antifungal treatments allows the advance of the disease
and the development of extensive fibrosis compromising severely and permanently
respiratory and adrenal functions, thus altering the patient"s quality of life
and even causing his/her death.
PMID- 29940545
TI - [Cardiovascular effects of new non-insulinic anti-diabetes drugs].
AB - Diabetes mellitus is currently a serious public health problem worldwide, that
increases the risk of presenting microvascular and macrovascular complications.
Although achieving the recommended blood glucose goals reduces the risk of
microvascular complications, the effect of the drugs used to treat hyperglycemia
on macrovascular complications and cardiovascular death is a cause for concern.
In this context, the regulatory agencies have modified the regulations for the
approval of new drugs in diabetes, by adding the need to demonstrate that they
are capable of lowering blood glucose levels together with a solid assessment of
cardiovascular safety. The objective of this study is to review the
cardiovascular effects of the new families of non-insulin drugs, with special
emphasis on their effect on the risk of major cardiovascular events. In recent
years, it has finally been confirmed that some of the drugs used to treat
diabetes are not only safe from a cardiovascular point of view, but have even
shown capacity to reduce the risk of cardiovascular disease in type 2 diabetes
mellitus. The evidence obtained determined the updating of some current
therapeutic guidelines when cardiovascular risk should be considered a
fundamental variable at the time of therapeutic choice in patients with diabetes.
PMID- 29940546
TI - [IgG4 related disease presenting as panhypopituitarism and perimacular scotoma].
AB - IgG4-related disease (IgG4-RD) is a recently described systemic entity of unknown
origin. It predominantly affects older men and has distinctive histopathologic
features as storiform fibrosis, obliterative phlebitis, dense lymphoplasmacytic
infiltrate with immunostaining for IgG4, and it may be associated with elevated
serum levels of IgG4. Although any organ can be affected, pituitary gland is
rarely involved. We describe the case of a 36-year-old man who presented with
headaches, impaired vision, panhypopituitarism with diabetes insipidus and an
infiltrative lesion mainly of infundibulum and pituitary. We arrived at diagnosis
of IgG4-RD by pituitary biopsy. A successful response to treatment with
immunosuppressive doses of corticosteroids was achieved.
PMID- 29940547
TI - [Subcutaneous injection of metallic mercury. The importance of early removal].
AB - Accidental or intentional subcutaneous or intramuscular injection of metallic
mercury is an uncommon form of intoxication. We present the case of a 22 year-old
man, who had psychotic disorders and autoaggressive behavior, with a preceding
history of self-injection of mercury into the soft tissues of the neck, thorax
and abdomen. Clinical examination, radiographs, and computed tomography showed
the affected area. Mercury was measured in blood and urine. The mercury was
surgically resected from the affected areas. Early detection and removal of
mercury from the body by physical removal or chelation is required to prevent
short- and long-term toxicity.
PMID- 29940548
TI - [Timely diagnosis of disseminated paracoccidioidomycosis in an immunocompetent
adult].
AB - Paracoccidioidomycosis is endemic in subtropical rainforests of Latin America.
Acute/subacute presentations involve an aggressive dissemination throughout the
lymphatic system, while chronic forms (more frequent) arise as differential
diagnosis for other conditions involving lung, oropharynx, skin, and eventually
the brain. We present the case of a man referred for evaluation and treatment of
a possible lung tumor with brain metastasis. The finding of multibudded yeasts
and the microbiological isolation of a dimorphic fungus identified as
Paracoccidioides sp. from a brain biopsy prompted a cardinal change in prognosis
and treatment. This case alerts on the importance of considering systemic fungal
diseases as differential diagnosis of compatible clinical presentations in
patients who had lived in, or visited, endemic areas.
PMID- 29940549
TI - [Autochthonous case of spotted fever caused by Rickettsia parkeri in Ensenada,
Buenos Aires].
AB - We present a case of spotted fever occurred in an adult residing in Ensenada,
Buenos Aires province in February 2016. The patient presented with an acute
febrile syndrome associated with a skin necrotic lesion on the left leg secondary
to a tick bite. The general symptoms were a maculopapular rash, headache,
myalgia, and arthralgias. Seroconversion of anti-Rickettsia specific IgG
antibodies confirmed recent infection. The nucleotidic and aminoacidic sequences
of a gltA gen fragment matched 100% the sequences of R. parkeri strains from
Argentina and other countries of America. The patient responded well to treatment
with doxycycline.
PMID- 29940550
TI - [Clinical polymorphism of anorectal lymphogranuloma venereum in Buenos Aires
City].
AB - From 2003 to date there has been a rising number of reports from developed
countries on cases of lymphogranuloma venereum with anorectal localization in HIV
infected men who have sex with men. This localization differs from the classical
inguinal abscesses which are typical of the disease in the tropics. The objective
of this work is to document the presence of anorectal lymphogranuloma venereum in
Buenos Aires and to describe its varied clinical manifestations. In the context
of a systematic survey of rectal chlamydial infection, in just one trimester,
eight cases of lymphogranuloma venereum caused by Chlamydia trachomatis biovar
LGV were identified in HIV-infected men who have sex with men. The most frequent
anorectal manifestations were pus, tenesmus, rectal urgency, and mucous or
haemopurulent discharge. The proctitis was mostly mild or moderate and, in some
cases, it was accompanied by perianal lesions. Given the great polymorphism and
unspecificity of the clinical manifestations of the disease, we warn on the
presence of this form of rectal lymphogranuloma venereum in our setting. If
Chlamydia trachomatis is detected, it should be genotyped, not only for the
correct diagnosis and treatment but also for epidemiological surveillance. Where
genotyping is not available, the disease must be considered as caused by the LGV
biovar and treated accordingly.
PMID- 29940551
TI - [Thymoma presenting as cardiac tamponade].
PMID- 29940553
TI - [The weight of words].
PMID- 29940552
TI - [Intravenous injection of metallic mercury in a foot].
PMID- 29940554
TI - [Sustained validity of the University Reform of 1918].
PMID- 29940555
TI - [The scientific production of public hospitals. Medical care, teaching and
research: a utopian virtuous circle?]
PMID- 29940556
TI - [Medical care, teaching and research: a possible utopia].
PMID- 29940557
TI - Thrombomodulin and Endothelial Dysfunction: A Disease-Modifier Shared between
Malignant Hypertension and Atypical Hemolytic Uremic Syndrome.
AB - Thrombomodulin (TM) is an endothelial glycoprotein that is present in all blood
vessels. Five percent of all patients with atypical hemolytic uremic syndrome
(aHUS) have mutations in the gene coding for TM, with a peak presentation in
young children. Mutations often translate into quantitative and qualitative
abnormalities of this endothelial glycoprotein. Outcome of the TM-associated aHUS
is relatively poor with frequent relapses after transplantation despite its
membrane-bound character. We observed a woman presenting with malignant
hypertension (MHT) and associated kidney, brain, cardiac, and hematological
involvement with thrombotic microangiopathy on kidney biopsy. She had a
documented mutation of the gene coding for TM, which was associated with both
aHUS and an increased risk for venous and arterial thrombosis. As TM has anti
coagulant, anti-inflammatory, and cytoprotective properties and also attenuates
alternative complement activation, this glycoprotein could play an active role in
other diseases with endothelial involvement apart from aHUS. We discuss the
potential role of TM in the pathophysiology of various endotheliopathies
including MHT. We also provide a framework for future therapeutic options.
PMID- 29940558
TI - Harmonization of the Genetic Code Effectively Enhances the Recombinant Production
of the Major Birch Pollen Allergen Bet v 1.
AB - BACKGROUND: Enhancing the quality and yield of protein production in heterologous
expression systems is an important issue for developing new biopharmaceuticals.
It has been shown that the dynamics of protein folding is influenced by codon
frequencies. As codon usage frequencies are species specific, this can affect
heterologous protein expression. In this respect, "codon harmonization," that is,
the usage of synonymous codons with usage frequencies in the host resembling the
usage frequencies in the native organism, is a promising strategy. As recombinant
proteins are important tools in the area of allergy research, we investigated in
this study the influence of codon harmonization on the production of the major
birch pollen allergen Bet v 1.0101. METHODS: To accomplish this task, parallel
production of several batches of rBet v 1, BWT, together with a harmonized
variant, BH, was applied. The expression yield of soluble and insoluble protein
was assayed via densitometric analysis of -SDS-PAGEs for every batch. The quality
of purified proteins was assessed with a variety of physicochemical methods
including mass spectrometry, circular dichroism, dynamic light scattering,
Fourier transform infrared spectroscopy, in vitro degradation, and 1-anilino-8
naphthalene sulfonate-binding assays. Patients' IgE reactivity was tested in
enzyme-linked immunosorbent assays and rat basophil mediator release experiments.
RESULTS: No significant differences in the ligand-binding capacity and secondary
structure elements, as well as, in immunological assays could be found; however,
the production yield was drastically increased for BH. CONCLUSION: We could show
that codon harmonization is a powerful method to enhance protein yields in
heterologous expression systems and should be considered especially for difficult
to-express proteins.
PMID- 29940559
TI - Uncaria rhynchophylla Ameliorates Parkinson's Disease by Inhibiting HSP90
Expression: Insights from Quantitative Proteomics.
AB - BACKGROUND/AIMS: Uncaria rhynchophylla, known as "Gou-teng", is a traditional
Chinese medicine (TCM) used to extinguish wind, clear heat, arrest convulsions,
and pacify the liver. Although U. rhynchophylla has a long history of being often
used to treat central nervous system (CNS) diseases, its efficacy and potential
mechanism are still uncertain. This study investigated neuroprotective effect and
the underlying mechanism of U. rhynchophylla extract (URE) in MPP+-induced SH
SY5Y cells and MPTP-induced mice. METHODS: MPP+-induced SH-SY5Y cells and MPTP
induced mice were used to established Parkinson's disease (PD) models.
Quantitative proteomics and bioinformatics were used to uncover proteomics
changes of URE. Western blotting was used to validate main differentially
expressed proteins and test HSP90 client proteins (apoptosis-related, autophagy
related, MAPKs, PI3K, and AKT proteins). Flow cytometry and JC-1 staining assay
were further used to confirm the effect of URE on MPP+-induced apoptosis in SH
SY5Y cells. Gait analysis was used to detect the behavioral changes in MPTP
induced mice. The levels of dopamine (DA) and their metabolites were examined in
striatum (STR) by HPLC-EC. The positive expression of tyrosine hydroxylase (TH)
was detected by immunohischemical staining and Western blotting. RESULTS: URE
dose-dependently increased the cell viability in MPP+-induced SH-SY5Y cells.
Quantitative proteomics and bioinformatics results confirmed that HSP90 was an
important differentially expressed protein of URE. URE inhibited the expression
of HSP90, which further reversed MPP+-induced cell apoptosis and autophagy by
increasing the expressions of Bcl-2, Cyclin D1, p-ERK, p-PI3K p85, PI3K
p110alpha, p-AKT, and LC3-I and decreasing cleaved caspase 3, Bax, p-JNK, p-p38,
and LC3-II. URE also markedly decreased the apoptotic ratio and elevated
mitochondrial transmembrane potential (DPsim). Furthermore, URE treatment
ameliorated behavioral impairments, increased the contents of DA and its
metabolites and elevated the positive expressions of TH in SN and STR as well as
the TH protein. CONCLUSIONS: URE possessed the neuroprotective effect in vivo and
in vitro, regulated MAPK and PI3K-AKT signal pathways, and inhibited the
expression of HSP90. U. rhynchophylla has potentials as therapeutic agent in PD
treatment.
PMID- 29940560
TI - Cardiac Valve Annulus Diameters in Extremely Preterm Infants: A Cross-Sectional
Echocardiographic Study.
AB - BACKGROUND: With the increasing incidence of births of very preterm very-low
birth-weight infants, there is a demand for echocardiographic reference values of
cardiac dimensions. OBJECTIVES: The aim of this study was to provide reference
values of cardiac valve annulus diameters in a cohort of extremely preterm very
low-birth-weight neonates and to correlate these with patient characteristics.
METHODS: Valve diameters of 376 infants of < 32 weeks' gestation and with a birth
weight of <=2,000 g were measured using 2-dimensional echocardiography.
Correlations between valve diameters and patient characteristics (birth
length/weight, body surface area, gestational age, and sex) were assessed. Birth
weight was used to establish linear regression models. Inter- and intraobserver
agreement was assessed through intraclass correlation coefficient (ICC) analysis.
RESULTS: Substantial variability was found (aortic valve mean [standard
deviation; range]: 5.0 mm [0.6; 3.7-6.5]; pulmonic valve: 5.8 mm [0.8; 3.4-7.9];
mitral valve: 8.0 mm [1.0; 5.5-10.5]; tricuspid valve: 7.6 mm [1.2; 4.9-10.6]).
There was a moderate correlation between birth weight and valve diameter (R2
aortic valve: 0.36; pulmonic valve: 0.20; mitral valve: 0.24; tricuspid valve:
0.24). Adequate intraobserver (ICC range 0.74-0.91) and interobserver agreement
(ICC range 0.77-0.89) was found. CONCLUSIONS: Our study provides ready-to-use
reference values for cardiac valve annulus diameters for extremely preterm
infants.
PMID- 29940561
TI - Exploring Cognitive Concomitants of Mental Fatigue in Patients with Coronary
Artery Disease.
AB - OBJECTIVE: Fatigue and reduced exercise capacity are common concomitants of
coronary artery disease (CAD). They are known to be associated with the
deterioration in mental health, including emotional and cognitive status.
However, the precise nature of the inter-relationship is poorly understood. The
aim of this study was to investigate the relationship between fatigue and
exercise capacity on the one hand and changes in cognitive functioning on the
other, to generate new heuristics for clinical management and outcome prediction
of CAD. METHODS: A cross-sectional study included 827 in-patients (58 +/- 9
years, 75% men) with CAD. Patients were evaluated for demographic, cardiac
characteristics, and exercise capacity. The Multidimensional Fatigue Inventory-20
was used to assess fatigue, the Mini Mental State Examination for global
cognitive function, the Digit Span Test, Digit Symbol Test, and Trail Making Test
for executive aspects of cognitive functioning, and the Hospital Anxiety and
Depression Scale for anxiety and depression symptom severity. RESULTS: Using
multiple regression analysis, after adjusting for possible confounders such as
anxiety and depression, mental fatigue was associated with several executive
aspects of cognitive function including short-term memory (Digit Symbol Test
pairs recalled correctly [beta = -0.127, p < 0.005]), psychomotor performance
(time to complete the Digit Symbol Test [beta = 0.089, p < 0.03]), and cognitive
processing speed (Trail Making Test A [beta = 0.081, p < 0.05]). CONCLUSION: In
rehabilitating CAD patients, certain aspects of executive functioning were
independently associated with mental fatigue. These findings suggest that the
subjective experience of mental fatigue, rather than reduced exercise capacity,
is significantly associated with cognitive function.
PMID- 29940562
TI - Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases.
AB - High mobility group box-1 (HMGB-1), a typical damage-associated molecular pattern
protein released from various cells, was first identified in 1973. It is usually
stored in the nuclei of cells. Several modifications of HMGB-1 promote its
translocation to the cytosol, and it is actively or passively released from
cells. When outside of the cells, HMGB-1is crucial in inflammation. It exerts its
biological functions via interaction with its receptors, including receptor for
advanced glycation end products (RAGE) and Toll-like receptor 4(TLR4). A large
number of studies showed a close link between inflammation and thrombosis. This
review demonstrated the increased expression of HMGB-1 in thrombosis-related
diseases, including coronary artery disease, stroke, peripheral arterial disease,
disseminated intravascular coagulation, and venous thrombosis. Besides, it
summarized the current understanding of the emerging link between HMGB-1 and
thrombosis from three aspects: platelet, NETs, and coagulation and fibrinolysis
factors. Finally, it explored the possible therapeutic strategies targeting HMGB
1 for treating thrombosis-related diseases.
PMID- 29940563
TI - Maternal Intrapartum Antibiotic Administration and Infantile Colic: Is there a
Connection?
AB - BACKGROUND: The aetiology of infantile colic remains unknown. However, altered
gut microbiota composition has been reported in children with the disorder.
OBJECTIVE: The objective of this study was to determine the associations between
perinatal factors potentially affecting gut colonization and infantile colic.
METHODS: Altogether 48 infants with colic and 29 controls were selected from 2
ongoing clinical studies. Infants with and without colic were comparable with
regard to their background characteristics. RESULTS: A significant difference was
detected in intrapartum antibiotic use and breastfeeding rates between infants
with and without colic. The association between exposure to intrapartum
antibiotics and infantile colic remained statistically significant after
adjusting for potential confounding factors. CONCLUSIONS: Since intrapartum
antibiotic exposure may have an effect on early gut colonization, our finding is
consistent with the association between aberrant early gut microbiota composition
and development of colic. Antibiotic-exposed neonates may represent a novel
target group for preventive intervention studies.
PMID- 29940564
TI - Exosomes: The New Mediator of Peritoneal Membrane Function.
AB - Fibrosis and angiogenesis are the most common processes that result in
progressive peritoneal tissue remodeling and, eventually, peritoneal membrane
dysfunction. The role of exosomes, which contributes to intercellular
communication, in these processes has been neglected. Various biomolecules,
including DNA, mRNA, proteins, lipids, and particular certain miRNAs, can be
transferred by exosomes to local, neighboring and distal cells. Upon stimulation
by cytokines or other microenvironment stimuli, donor cells release a mass of
exosomes to peritoneal mesothelial cells, further affecting fibrosis and
angiogenesis. This important exosomes-mediated intracellular communication is
thought to regulate peritoneal membrane function. Understanding the molecular
mechanisms of these processes, targeting changes in exosomes and regulating
exosomal miRNAs will advance therapeutic methods for protecting peritoneal
membrane function.
PMID- 29940565
TI - False-Positive Rate in First-Trimester Screening Based on Ultrasound and Cell
Free DNA versus First-Trimester Combined Screening with Additional Ultrasound
Markers.
AB - OBJECTIVE: To determine whether screening for trisomy 21 based on first-trimester
combined screening (FTCS) with assessment of nasal bone (NB), tricuspid flow
(TCF), and ductus venosus flow (DVF) results in similar false-positive rates
compared to ultrasound and cell-free DNA (cfDNA) screening. METHODS: This is a
subanalysis of a prospective randomized controlled trial which was performed
between October 2015 and December 2016. Pregnant women with a normal first
trimester ultrasound examination at 11 to 13 weeks' gestation were randomized
into two groups: (1) FTCS with assessment of the NB, TCF, and DVF (extended FTCS
[eFTCS]), and (2) ultrasound + cfDNA screening. The false-positive rate in
screening for trisomy 21 was defined as the primary outcome parameter. RESULTS:
The study population consisted of 688 women in each study arm. In the eFTCS
group, the median delta fetal nuchal translucency thickness (NT) was 0.0 mm, free
beta-hCG and PAPP-A were 0.96 and 1.11 MoM, and NB, TCF, and DVF PIV were
abnormal in 0.9, 0.6, and 7.0% cases. In the ultrasound + cfDNA group, the median
delta NT was 0.0 mm. In 10 pregnancies the cfDNA analysis was uninformative and
the risk of trisomy 21 was based on eFTCS. There were no false-positive cases in
the ultrasound + cfDNA group, whereas the false-positive rates were between 0.9
and 2.2% with eFTCS. CONCLUSION: Screening for trisomy 21 based on ultrasound +
cfDNA has a lower false-positive rate than screening based on eFTCS.
PMID- 29940566
TI - Sensitization of Gastric Cancer Cells to 5-FU by MicroRNA-204 Through Targeting
the TGFBR2-Mediated Epithelial to Mesenchymal Transition.
AB - BACKGROUND/AIMS: Gastric cancer (GC) is the most common gastrointestinal
malignancy, causing cancer-related deaths in East Asia. MicroRNAs (miRNAs) are
small non-coding RNAs aberrantly expressed in human tumors. In this study, we aim
to investigate the roles of miR-204 in the epithelial to mesenchymal transition
(EMT)-associated chemosensitivity. METHODS: The expression of miR-204 was
detected in clinical tumor samples and GC cell lines by real time PCR. Tumor
cell's growth, invasion, and migration were measured by MTT assay, wound healing
assay, and transwell invasion assay, respectively. Western blot method was used
to detect the protein levels of indicated genes. Luciferase reporter assay was
performed to validate the target gene of miR-204. The in vivo role of miR-204 was
measured using a xenograft mouse model of GC. RESULTS: By comparing the
expressions of miR-204 in human gastric tumors and their adjacent normal tissues,
it was disclosed that miR-204 was significantly downregulated in gastric tumors.
Moreover, miR-204 was downregulated in multiple GC cell lines compared with
normal gastric epithelial cells. Overexpression of miR-204 suppressed GC cells'
proliferation, invasion, and migration. It is noteworthy that 5-FU treatments
induced miR-204 expression and suppressed TGF-beta pathway. By establishment of 5
FU resistant GC cell line, it was revealed that miR-204 was significantly
downregulated in 5-FU resistant GC cells, representing mesenchymal features with
downregulation of epithelial marker, while mesenchymal markers were upregulated.
We identified TGFBR2 as a direct target of miR-204 by Western blot method and
luciferase assay in GC cells and tumor samples as well. In addition,
overexpression of miR-204 sensitized GC cells to 5-FU in vitro. Xenograft
experiments demonstrated that the combination of miR-204 and 5-FU efficiently
inhibited tumor growth and improved survival rate of mice as well. Eventually, we
illustrated the restoration of TGFBR2 in miR-204 overexpression GC cells, which
recovered resistance to 5-FU treatments compared with miR-204 overexpression GC
cells. CONCLUSION: This study describes a miRNA-based therapeutic strategy
against 5-FU resistance in GC, contributing to the development of anti
chemoresistance therapeutic agents.
PMID- 29940567
TI - Melatonin Loading Chitosan-Tripolyphosphate Nanoparticles: Application in
Attenuating Etoposide-Induced Genotoxicity in HepG2 Cells.
AB - Etoposide is one of the most effective chemotherapeutic agents used in the
treatment of various types of cancers. However, as a Topoisomerase II inhibitor,
during clinical use, several side effects may occur. In addition, in several in
vivo and in vitro studies, etoposide has been shown to have a range of genotoxic
effects including single and double strand breaks. Melatonin is an anti-aging and
antioxidant hormone synthesized from the pineal gland. The genoprotective,
antioxidant, and free radical scavenger properties of melatonin have been well
explained in various studies. The aim of this study was to explore whether
melatonin nanoparticles protects against etoposide-induced genotoxicity in the
HepG2 cell line. HepG2 cells (25 * 104 cells/well) were cultured in 24-well
plates: a control group and 3 melatonin and its nanoparticles + etoposide groups
(pre- and cotreatment conditions). Our results show that etoposide induced a
noticeable genotoxic effect in HepG2 cells. Melatonin reduced the effects of
etoposide significantly in both types of experiment conditions, through the
reduction of the level of DNA damage measured via comet assay. Furthermore,
melatonin decreased the intracellular reactive oxygen species generation. It also
increased the intracellular glutathione levels in HepG2 cells. Nano melatonin is
more effective than regular melatonin. The most protective effect was observed
with melatonin when it was administrated 24 h before etoposide treatment.
PMID- 29940569
TI - Reduced Prevalence of Severe Intraventricular Hemorrhage in Very Preterm Infants
Delivered after Maternal Preeclampsia.
AB - BACKGROUND: Very preterm (VPT) delivery after severe preeclampsia (PE) has been
associated with adverse perinatal outcome. It is unclear whether fetal exposure
to PE per se modifies the prevalence of neonatal morbidities associated with VPT
birth. OBJECTIVES: To evaluate neonatal morbidity in VPT infants exposed to
maternal PE compared to morbidity in nonexposed VPT infants. METHODS: This
retrospective study consisted of all inborn infants delivered before 30
gestational weeks admitted to a tertiary-level neonatal intensive care unit
between 1998 and 2014: 195 infants exposed to maternal PE were compared to 957
infants without maternal PE (background group). Prevalence rates of neonatal
morbidity, cerebral palsy (CP), and mortality at 2 years of age were obtained
from patient records. RESULTS: The PE group had a lower median (IQR) birth weight
(795 [262] g) and a higher median gestational age (GA) (27 [3] weeks) at birth
than the background group (890 [385] g and 26 [3] weeks, respectively; both p <
0.001). Exposure to maternal PE was associated with lower rates of severe
intraventricular hemorrhage (IVH) (2 vs. 11%), retinopathy of prematurity
requiring treatment (2 vs. 7%), mortality (9 vs. 15%), and CP (4 vs. 8%).
Exposure to PE remained associated with a reduced prevalence of severe IVH (OR
0.17, 95% CI 0.05-0.57) after adjustment for GA, multiple birth, Apgar score,
delivery mode, sex, and antenatal steroid treatment. CONCLUSION: Fetal exposure
to PE is associated with a decreased rate of severe IVH following VPT birth.
Studies on underlying mechanisms may provide a basis for prevention of IVH in the
VPT infant.
PMID- 29940568
TI - Galphai Proteins are Indispensable for Hearing.
AB - BACKGROUND/AIMS: From invertebrates to mammals, Galphai proteins act together
with their common binding partner Gpsm2 to govern cell polarization and planar
organization in virtually any polarized cell. Recently, we demonstrated that
Galphai3-deficiency in pre-hearing murine cochleae pointed to a role of Galphai3
for asymmetric migration of the kinocilium as well as the orientation and shape
of the stereociliary ("hair") bundle, a requirement for the progression of mature
hearing. We found that the lack of Galphai3 impairs stereociliary elongation and
hair bundle shape in high-frequency cochlear regions, linked to elevated hearing
thresholds for high-frequency sound. How these morphological defects translate
into hearing phenotypes is not clear. METHODS: Here, we studied global and
conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both
Galphai proteins. Comparative analyses of global versus Foxg1-driven conditional
mutants that mainly delete in the inner ear and telencephalon in combination with
functional tests were applied to dissect essential and redundant functions of
different Galphai isoforms and to assign specific defects to outer or inner hair
cells, the auditory nerve, satellite cells or central auditory neurons. RESULTS:
Here we report that lack of Galphai3 but not of the ubiquitously expressed
Galphai2 elevates hearing threshold, accompanied by impaired hair bundle
elongation and shape in high-frequency cochlear regions. During the crucial
reprogramming of the immature inner hair cell (IHC) synapse into a functional
sensory synapse of the mature IHC deficiency for Galphai2 or Galphai3 had no
impact. In contrast, double-deficiency for Galphai2 and Galphai3 isoforms results
in abnormalities along the entire tonotopic axis including profound deafness
associated with stereocilia defects. In these mice, postnatal IHC synapse
maturation is also impaired. In addition, the analysis of conditional versus
global Galphai3-deficient mice revealed that the amplitude of ABR wave IV was
disproportionally elevated in comparison to ABR wave I indicating that Galphai3
is selectively involved in generation of neural gain during auditory processing.
CONCLUSION: We propose a so far unrecognized complexity of isoform-specific and
overlapping Galphai protein functions particular during final differentiation
processes.
PMID- 29940570
TI - Gestational Age and the Cord Blood Lipidomic Profile in Late Preterm and Term
Infants.
AB - BACKGROUND: Lipid metabolism is vital to fetal development and cardiometabolic
health and the final weeks of gestation are known to be a time of intense
metabolic activity. New techniques such as lipidomics allow investigation of a
complex lipidomic profile in infants. OBJECTIVES: This research aimed to (1)
describe variations in lipidomic profile in late preterm and term infants and (2)
compare variations to an adult lipidomic profile with known clinical
implications. METHODS: The Barwon Infant Study (n = 1,074) is a population
derived pre-birth cohort study. The lipidomic profile of cord blood was measured
by liquid chromatography-mass spectrometry in 225 participants and the
association between gestational age and lipidomic profile was investigated using
multiple linear regression adjusting for birth weight, exposure to labour, and
infant sex. Patterns of association with gestational age across the lipidomic
profile were compared with associations between body mass index (BMI) and
lipidomic profile observed among adults in the San Antonia Family Heart Study (n
= 994). RESULTS: Gestational age was independently associated with the abundances
of 39% of lipid species. Variations in the lipidomic profile with increasing
gestational age were comparable to some variations observed in association with
increasing BMI among adults. CONCLUSION: There is a strong relationship between
gestational age and the cord blood lipid profile at birth, providing further
evidence for the importance of metabolic changes of late gestation. A number of
the variations in the lipid profile with increasing gestational age are analogous
to differences observed in the adult lipid profile with an increasing BMI.
PMID- 29940571
TI - Thymic Stromal Lymphopoietin Signaling Pathway Inhibition Attenuates Airway
Inflammation and Remodeling in Rats with Asthma.
AB - BACKGROUND/AIMS: Thymic stromal lymphopoietin (TSLP) is a cytokine that plays
diverse roles in the regulation of immune responses. However, a detailed
understanding of the TSLP signaling pathway in asthma remains elusive. In this
study, we aimed to investigate the role of the TSLP signaling pathway in asthma
and its effect on airway inflammation and remodeling. METHODS: Forty Sprague
Dawley (SD) rats were evenly classified into control, asthma, IgG2a mAb and anti
TSLP mAb groups. Ovalbumin (OVA)-induced asthma models were successfully
established. Blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples
were prepared. Total BALF leukocytes were counted, and the proportions of
different leukocyte types were determined. Reverse transcription quantitative
polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to
determine the mRNA and protein levels of TSLP, OX40L, alpha-smooth muscle actin
(alpha-SMA, a marker of airway remodeling in asthma) and collagen I in the
plasma. Enzyme-linked immunosorbent assay (ELISA) was carried out to measure the
concentrations of TSLP, OX40L, and other inflammatory factors, such as interferon
(IFN)-gamma, interleukin (IL)-4, IL-5 and IL-13, in the plasma. RESULTS: Compared
with the control group, there were more leukocytes, increased EOS and LYM
proportions, higher Underwood and PAS scores, increased WTt, WTm, WAt/A0,
WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and collagen I mRNA and protein
levels, and higher SLP, OX40L, IL-4, IL-5 and IL-13 levels, but lower MON
proportions and IFN-gamma levels in the asthma and IgG2a mAb groups. Compared
with the asthma and IgG2a mAb groups, there were less leukocytes, decreased EOS
and LYM proportions, lower Underwood and PAS scores, decreased WTt, WTm, WAt/A0,
WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and Collagen I mRNA and protein
levels, and lower levels of SLP, OX40L, IL-4, IL-5 and IL-13, but higher MON
proportions and IFN-gamma levels in the anti-TSLP mAb group. WTm and WTt were
positively associated with the TSLP, OX40L, alpha-SMA and collagen-I levels in
the rat lung tissues. CONCLUSION: The results indicate that TSLP may be an
important contributor for asthma development as TSLP signaling blockade
attenuates airway inflammation and remodeling in asthmatic rats.
PMID- 29940572
TI - Association of Plasma Cortisol Levels with Clinical Characteristics of Suicide
Attempters.
AB - OBJECTIVE: There is evidence that suicidal behavior, among others, is an abnormal
response to stress caused by a dysfunction in the activity of hypothalamus
pituitary-adrenal axis, and that cortisol levels are low in a considerable number
of people attempting suicide. In this study, we aimed to search for associations
of plasma cortisol levels with the clinical characteristics of a group of
psychiatric suicide attempters. METHOD: The cortisol was measured in the morning
in 200 psychiatric patients hospitalized after a suicide attempt, with diagnoses
of major depressive disorder, bipolar disorder, psychosis, and
personality/adjustment disorder, and compared to the levels of 138 healthy
controls. Comparisons were also made for diagnostic subgroups and across
diagnoses, with regard to depressive symptomatology, mode of attempt, suicide
intent, number of attempts, and age. RESULTS: Cortisol levels were significantly
lower for the whole group of attempters compared to controls. Furthermore, low
cortisol levels characterized attempters with personality/adjustment disorder,
higher depressive symptomatology, low suicide intent, non-violent attempt mode,
repeated attempts, and of younger age. CONCLUSIONS: Certain clinical
characteristics were identified in attempters with low cortisol levels. In
previous studies, low cortisol levels have been associated with impairments in
cognitive control, decision-making, and emotional processing that may lead, in
the presence of stressors, to suicidal behavior, frequently with non-fatal
outcome. Adding plasma cortisol levels to demographic and psychopathological data
may help in identifying a subpopulation of attempters with neurocognitive
deficits linked to dysfunction of Hypothalamic-Pituitary-Adrenal-axis activity,
with implications for treatment.
PMID- 29940573
TI - Prevalence of Multiple Sclerosis in Iceland.
AB - BACKGROUND: In this study, we examined multiple sclerosis (MS) point prevalence
in the well-defined island population of Iceland. METHODS: This study included
all registered residents of Iceland with MS on the prevalence day, December 31,
2007. All included patients met at least one of the following criteria: McDonald
criteria; Poser criteria for clinically definite MS, laboratory-supported
definite MS, clinically probable MS; or criteria for primary progressive MS. The
patients' medical records were reviewed, including all available MRI data
acquired prior to the prevalence day. RESULTS: We identified 526 patients, of
whom 73% (382) were women. The crude point prevalence of MS was 167.1 per 100,000
population on the prevalence day. With age adjustment made to the 2000 U.S.
population, the prevalence was 166.5 per 100,000 population. The mean patient age
on the prevalence day was 47 years(range 13-89) for both men and women. The mean
age at diagnosis was 36 years (range 13-77): 35 years for women and 36 years for
men. CONCLUSION: MS prevalence was high in Iceland compared to the prevalence
mentioned in reports from most of the world, and was similar to prevalence rates
in other Nordic countries.
PMID- 29940574
TI - Generation and Role of Oscillatory Contractions in Mouse Airway Smooth Muscle.
AB - BACKGROUND/AIMS: Tetraethylammonium chloride (TEA) induces oscillatory
contractions in mouse airway smooth muscle (ASM); however, the generation and
maintenance of oscillatory contractions and their role in ASM are unclear.
METHODS: In this study, oscillations of ASM contraction and intracellular Ca2+
were measured using force measuring and Ca2+ imaging technique, respectively.
TEA, nifedipine, niflumic acid, acetylcholine chloride, lithium chloride, KB
R7943, ouabain, 2-Aminoethoxydiphenyl borate, thapsigargin, tetrodotoxin, and
ryanodine were used to assess the mechanism of oscillatory contractions. RESULTS:
TEA induced depolarization, resulting in activation of L-type voltage-dependent
Ca2+ channels (LVDCCs) and voltage-dependent Na+ (VNa) channels. The former
mediated Ca2+ influx to trigger a contraction and the latter mediated Na+ entry
to enhance the contraction via activating LVDCCs. Meanwhile, increased Ca2+
activated Cl- channels, inducing depolarization that resulted in contraction
through LVDCCs. In addition, the contraction was enhanced by intracellular Ca2+
release from Ca2+ stores mediated by inositol (1,4,5)-trisphosphate receptors
(IP3Rs). These pathways together produce the contractile phase of the oscillatory
contractions. Furthermore, the increased Ca2+ activated the Na+-Ca2+ exchanger
(NCX), which transferred Ca2+ out of and Na+ into the cells. The former induced
relaxation and the latter activated Na+/K+-ATPase that induced hypopolarization
to inactivate LVDCCs causing further relaxation. This can also explain the
relaxant phase of the oscillatory contractions. Moreover, the depolarization
induced by VNa channels and NCX might be greater than the hypopolarization caused
by Na+/K+-ATPase alone, inducing LVDCC activation and resulting in further
contraction. CONCLUSIONS: These data indicate that the TEA-induced oscillatory
contractions were cooperatively produced by LVDCCs, VNa channels, Ca2+-activated
Cl- channels, NCX, Na+/K+ ATPase, IP3Rs-mediated Ca2+ release, and extracellular
Ca2+.
PMID- 29940575
TI - Knockdown of MiR-20a Enhances Sensitivity of Colorectal Cancer Cells to Cisplatin
by Increasing ASK1 Expression.
AB - BACKGROUND/AIMS: Platinum-based chemotherapy is one of the most important
strategies for treatment of colorectal cancer. To improve the therapeutic
efficiency, adjuvant drugs were sought to sensitize colorectal cancer cells to
platinum-based agents such as cisplatin. As previous research has shown that
miRNAs are associated with chemosensitivity, we aimed to alter miRNA regulation
in colorectal cancer cells to increase their chemosensitivity. METHODS: MTT
assays were performed to determine the viability of HT29, SW480, and LoVo cells.
Quantitative real time polymerase chain reaction (qRT-PCR) was performed to
examine the expression of miR-20a in these cell lines. Regulation of the miR
20a/ASK1 axis was confirmed by western blotting and luciferase reporter assays.
After treatment with miR-20a inhibitor (anti-miR-20a) and cisplatin, production
of reactive oxygen species (ROS), mitochondrial membrane potential, and apoptosis
were measured by flow cytometry. Activation of ASK1, Bcl-xl, JNK, and caspase-9,
7, and -3 was detected by western blotting. RESULTS: miR-20a was overexpressed in
colorectal cancer cell lines. Furthermore, knockdown of miR-20a increased the
sensitivity of colorectal cancer cells to cisplatin treatment in vitro and in
vivo. We demonstrated that the ASK1 gene was the target of miR-20a, and knockdown
of miR-20a increased the expression of ASK1 in colorectal cancer cells. As
cisplatin treatment induced production of ROS, knockdown of miR-20a enhanced ROS
signaling through promoting the phosphorylation of ASK1. Phosphorylation of JNK
and the subsequent mitochondrial apoptosis were triggered by the combination of
cisplatin and anti-miR-20a. CONCLUSIONS: Knockdown of miR-20a enhanced
sensitivity of colorectal cancer cells to cisplatin through the ROS/ASK1/JNK
pathway.
PMID- 29940576
TI - Similarities in the Computed Tomography Appearance in alpha1-Antitrypsin
Deficiency and Smoking-Related Chronic Obstructive Pulmonary Disease in a Smoking
Collective.
AB - BACKGROUND: Emphysematous destruction of lung parenchyma visible in computed
tomography (CT) can be attributed to chronic obstructive pulmonary disease (COPD)
or to alpha1-antitrypsin deficiency (AATD). OBJECTIVES: We evaluated if visual
semiquantitative phenotyping of CT data helps identifying individuals with AATD
in a group of smokers with severe emphysema and airflow limitation. METHOD: n =
14 patients with AATD and n = 15 with COPD and a minimum of 10 pack years
underwent CT, clinical assessment, and full-body plethysmography. The extent and
type of emphysema as well as large and small airway changes were rated
semiquantitatively for each lobe using a standardized previously published
scoring system. Lastly, a final diagnosis for each patient was proposed. RESULTS:
AATD had a significantly lower mean emphysema score than COPD, with 8.9 +/- 3.4
versus 11.9 +/- 3.2 (p < 0.001), respectively. Within both groups, there was
significantly more emphysema in the lower lobes (p < 0.05-0.001). The COPD group
showed an upper- and middle-lobe predominance of emphysema distribution when
compared to the AATD group (p < 0.001). Centrilobular (CLE) and panlobular (PLE)
emphysema patterns showed a uniform distribution within both groups, with a CLE
predominance in the upper lung and a PLE predominance in the lower lung regions.
AATD and COPD both showed significantly more airway changes in lower lobes
compared to upper lobes (p = 0.05-0.001), without significant differences between
both groups. CONCLUSION: The typical emphysema distribution patterns seen on CT
traditionally assigned to AATD and COPD were of little use in discriminating both
entities. Also, airway changes could not contribute to a more precise
differentiation. We conclude that a concise standardized phenotyping-driven
approach to chest CT in emphysema is not sufficient to identify patients with
AATD in a cohort of smokers with advanced emphysema.
PMID- 29940577
TI - Distinctive Olfactory Pattern in Parkinson's Disease and Non-Neurodegenerative
Causes of Hyposmia.
AB - BACKGROUND: Olfactory dysfunction is common in Parkinson's disease (PD). The
characteristics of the hyposmia in PD have not been well defined. OBJECTIVE: To
characterize the pattern of the olfactory deficit in PD and in other non
neurodegenerative aetiologies of hyposmia. METHODS: We evaluated 36 PD patients,
20 patients with hyposmia secondary to acute respiratory infection (ARI), and 19
patients with hyposmia secondary to traumatic brain injury (TBI). For comparison
purposes, we included a group of 15 controls age and sex matched with PD
patients. PD patients were classified based on disease duration and severity in
de novo PD, and PD with and without chronic levodopa-related complications. The
Barcelona Smell Identification Test was applied to all participants. RESULTS: For
the first cranial nerve odours, PD patients scored lower than controls on smell
detection (85.28 vs. 97.67%, p = 0.006), definition (79.58 vs. 93.33%, p =
0.007), recognition (63.33 vs. 81%, p = 0.020), and forced choice (58.06 vs. 82%,
p < 0.001). Compared with ARI, forced choice was significantly better in PD
patients (p < 0.001), but no differences were found regarding other olfactory
characteristics. TBI patients showed significantly lower scores than the other
study groups in all the olfaction items. For the fifth cranial nerve odours,
recognition (p = 0.003) and identification (p = 0.019) were lower in the TBI
group than in the others. No differences were found among PD subgroups regarding
any olfactory characteristic. CONCLUSIONS: A differential pattern of hyposmia was
observed in PD patients compared to other non-neurodegenerative aetiologies.
Further studies with larger samples should replicate our results.
PMID- 29940578
TI - Assessing the Surgical Experience to Identify Risk Factors Associated with Severe
Retinopathy of Prematurity and Laser Intervention.
AB - BACKGROUND: Retinopathy of prematurity (ROP) is a known complication of preterm
birth and one of the leading causes of blindness. Known risk factors include low
gestational age (GA), birth weight, and oxygen exposure. It is unknown if there
are surgical risk factors associated with severe ROP. OBJECTIVES: Identify risk
factors of a neonatal surgical exposure associated with laser therapy for ROP.
METHODS: Institutional review of 76 infants with GA <=27 weeks or birth weight
<=800 g. Infant demographics and details of surgical experience were collected.
Infants who underwent a surgical procedure were analyzed to identify risk factors
associated with laser treatment for severe ROP. Surgical and nonsurgical infants
were compared to assess if the rate of laser intervention differed among
institutions/published data. Data were analyzed using the Mann-Whitney U test,
unpaired t test, OR and Fischer's exact test. RESULT: Out of 49 surgical infants,
11 underwent laser intervention. Infants undergoing laser had surgery at an
earlier postmenstrual age (PMA; 31.5 [29.3-39.4] weeks vs. 38.1 [31.3-42.5]
weeks, p = 0.01), were more likely to have an exploratory laparotomy (adjusted
odds ratio 1.3 [1.04-1.64], p = 0.02), and to undergo more surgical procedures (3
vs. 2, p = 0.04). CONCLUSION: At our institution, preterm infants who undergo a
surgical procedure prior to 32 weeks PMA and those having >=3 surgeries were at a
higher risk for progressing to laser intervention. Additional studies with larger
sample sizes are needed to assess if the risk factors we have identified remain
significant and to identify other possible risk factors.
PMID- 29940579
TI - Feasibility of Smartphone-Based Testing of Interference in Parkinson's Disease.
AB - BACKGROUND: Interference refers to learned associations and established behaviors
"interfering" with response to new material. It forms a core pillar of executive
functions, which are commonly affected in Parkinson's disease (PD). Cognitive
interference test (CIT) forms part of a smartphone application designed for
ambulatory assessment in PD. OBJECTIVE: The aims of this study were to establish
that CIT could effectively demonstrate interference and would perform comparably
to the Stroop Color-Word Test Victoria version (VST) despite PD-related motor
impairment. METHODS: Ninety-nine patients with PD were recruited. Initial
evaluation included CIT, VST, Montreal cognitive assessment (MOCA), and Movement
Disorders Society-sponsored revision of the -Unified Parkinson's Disease Rating
Scale (MDS-UPDRS-III). A group of patients underwent repeat assessment within 2
weeks. Thirty-four healthy controls were recruited for comparison. RESULTS:
Patients' mean age was 66.2 years, disease duration was 8.7 years, on-state MDS
UPDRS-III was 22, and MOCA total score was 27. CIT effectively generated
interference, whereby the total time taken to complete the incongruent task was
20% longer compared to that of the baseline task. CIT key test items demonstrated
convergent validity to VST (r = 0.478-0.644, p < 0.0001) and satisfactory
repeatability (intraclass correlation coefficient 0.46-0.808, p <= 0.0002).
Performance on key CIT test parameters deteriorated with increasing age (r =
0.225-0.478, p < 0.01) and MDS-UPDRS-III total score (r = 0.354-0.481, p <
0.0001). When compared to controls and patients with less motor impairment,
patients MDS-UPDRS-III > 30 took longer to complete CIT and VST and had lower
MOCA-attention sub-score, implying that the degree of motor impairment could not
be the sole explanation for reduced CIT performance. CONCLUSIONS: We established
that despite motor impairment, the novel approach of using smartphone technology
to test interference in PD patients is feasible.
PMID- 29940580
TI - Effectiveness, Costs and Patient Acceptance of a Conventional and a Biological
Treatment Approach for Carious Primary Teeth in Children.
AB - BACKGROUND: Over the last years, conventional restorations for the treatment of
active carious lesions (CL) in primary teeth have been challenged and a more
biological approach has been suggested. This approach involves less invasive
techniques that alter the environment of the CL isolating it from the cariogenic
biofilm and substrate. AIM: To investigate the cost-effectiveness and patient
acceptance of 2 treatment approaches for the treatment of deep CLs in primary
teeth in children. METHODS: This was a retrospective/prospective cohort study
carried out in 2 UK specialist hospital settings. Data on cost-effectiveness was
extracted retrospectively from clinical dental records of 246 patients aged 4-9
years. A prospective study design was used to explore patient acceptance of the 2
treatment approaches. One hundred and ten patients aged 4-9 years and their
carers completed 2 questionnaires on treatment acceptance. RESULTS: In total, 836
primary teeth that had received treatment with either approach were included.
More than 2 thirds (75.7%) of the restorations in the conventional approach were
of non-selective removal to hard dentine followed by pulpotomy (24.3%). In the
biological approach, most of the restorations were stainless steel crowns placed
with the Hall Technique (95%) followed by selective removal to firm dentine (5%).
The majority of the primary teeth remained asymptomatic after a follow-up period
of up to 77 months; 95.3% in the conventional and 95.8% in the biological arm.
When the treatment costs were analysed, a statistically significant difference
was found between the mean costs of the 2 approaches with a mean difference of
GBP 45.20 (Pound Sterling; p < 0.001), in favour of the biological approach. The
majority of the children and carers were happy with the conventional or
biological restorations. CONCLUSION: Although both approaches had similar
successful outcomes, the biological approach consisting mainly of Hall Technique
was associated with reduced treatment costs. Both approaches were accepted
favourably by the children and carers.
PMID- 29940581
TI - Developing Viscosity Modelling for Traditional Liquids in Egypt.
AB - OBJECTIVES: The aim of this study was to develop a low-cost methodology for
preparing different thickened liquids with different consistencies and
viscosities that mimic the viscosities of culturally relevant traditional
Egyptian liquids, which can be easily used in the fiberoptic-endoscopic
evaluation of swallowing. MATERIALS AND METHODS: The textures of 9 traditional
Egyptian liquids were quantified with the International Dysphagia Diet
Standardisation Initiative (IDDSI) Flow Test and spanned the entire range of the
IDDSI scale. We then developed texture-modified fluids that matched each dietary
fluid texture for endoscopic dysphagia assessment using a regionally available,
inexpensive, starch-based thickening agent. RESULTS: Our results indicate simple
methods of assuring that fluids used during swallowing testing with endoscopy can
be matched to dietary fluids to ensure appropriate dietary prescriptions for
people with dysphagia. The changes in the thickness and viscosity of the prepared
liquid samples were detected and studied separately. The measured samples include
some traditional Egyptian fluids (molokhia, lentil soup) in addition to
commercially available fluids and pudding. CONCLUSION: The method can be applied
to develop thickened liquids with different consistencies to model the
traditional, naturally thickened liquids in Egypt and many other developing
countries.
PMID- 29940582
TI - Role of Field Staining in the Cytological Assessment of Intraoperative Surgical
Specimens.
AB - OBJECTIVE: To study the role of Field staining in scrape smears for
intraoperative cytological (IOC) diagnosis. Specimens were assessed for
categorizing among benign and malignant lesions, lymph node status, and adequacy
of surgical cut margins as per specimen. Technique, adequacy, and quality were
assessed along with comparison of cytological diagnosis with final
histopathological diagnosis obtained on routine hematoxylin and eosin-stained
slides. STUDY DESIGN: A prospective observational study was conducted over a
period of 1 year from November 2016 to October 2017 in the Department of
Pathology of our Institute. RESULTS: 50 cases were studied, and scrape smears
were stained with Field stain. Results were satisfactory in terms of adequacy and
attaining the objectives of the study. A diagnostic accuracy of 98% was observed
with an average turnaround time of 5 min. A single case of low-grade glioma was
found to be discordant. CONCLUSIONS: Use of Field staining for intraoper-ative
cytological assessment of surgical specimens has 98% concordance with the final
histopathological diagnosis and achieved the aim of the study. With its low
costs, easy availability, short turnaround time, and simple technique, it will be
helpful in IOC as an alternative to present techniques especially in financially
constrained settings.
PMID- 29940583
TI - Survival of Immunoglobulins from Human Milk to Preterm Infant Gastric Samples at
1, 2, and 3 h Postprandial.
AB - BACKGROUND: Human milk immunoglobulins (Ig) are an important support for the
naive infant immune system; yet the extent to which these proteins survive within
the infant digestive tract, particularly for preterm infants, is poorly studied.
OBJECTIVES: Our objective was to evaluate the survival of human milk Igs in the
preterm stomach across postprandial time. METHODS: Human milk and infant gastric
samples were collected from 11 preterm (23-32 weeks gestational age) mother
infant pairs within 7-98 days postnatal age. Preterm gastric samples were
collected 1, 2, and 3 h after the beginning of the feeding. Samples were analyzed
for concentration of total IgA (secretory IgA [SIgA]/IgA), total secretory
component (SC/SIgA/SIgM), total IgM (SIgM/IgM), and IgG via enzyme-linked
immunosorbent assay. Ig-chain fragment peptides were determined using peptidomic
analysis. One-way analysis of variance with repeated measures followed by Tukey's
multiple comparison tests was applied. RESULTS: Concentrations of total IgA were
lower in the gastric contents at 3 h postprandial compared with human milk and
gastric contents at 1 and 2 h. Human milk SC/SIgA/SIgM, IgG, and total IgM
concentrations remained stable in the preterm stomach across postprandial time.
Peptide counts from the Ig alpha-chain and the Ig gamma-chain increased in
gastric contents from 1 to 2 h postprandial. Peptide counts from the human milk
Ig-chain, Ig-chain, and SC were stable across postprandial time. These peptides
from Ig-chains were not present in human milk but were released in the stomach
due to their partial degradation. CONCLUSIONS: Human milk total SC
(SIgA/SC/SIgM), total IgM, and IgG survived mostly intact through the preterm
infant stomach, while total IgA was -partially digested.
PMID- 29940584
TI - Effects of the TLR4/Myd88/NF-kappaB Signaling Pathway on NLRP3 Inflammasome in
Coronary Microembolization-Induced Myocardial Injury.
AB - BACKGROUND/AIMS: Coronary microembolization (CME) is a common complication of
acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI);
Myocardial inflammation, caused by CME, is the main cause of cardiac injury.
TLR4/MyD88/NF-kappaB signaling plays an important role in the development of
myocardial inflammation, but its effects on CME remain unclear. To assess the
cardiac protective effects of TAK-242 (TLR4 specific inhibitor) on CME-induced
myocardial injury, and explore the underlying mechanism. METHODS: Cardiac
function, serum c-troponin I level, microinfarct were examined by cardiac
ultrasound, myocardial enzyme assessment, HBFP staining. The levels of
TLR4/MyD88/NF-kappaB signaling and NLRP3 inflammasome pathway were detected by
ELISA, qRT-PCR and western blot. RESULTS: The results showed inflammatory
responses in the myocardium after CME, with increased expression levels of pro
inflammatory factors TNF-alpha, IL-1beta and IL-18. Meanwhile, TLR4/MyD88/NF
kappaB signaling and the NLRP3 inflammasome were involved in the inflammatory
process. TAK-242 administration before CME effectively inhibited the inflammatory
response in the rat myocardium after CME and reduced myocardial injury, mainly by
inhibiting TLR4/ MyD88/NF-kappaB signaling and reducing NLRP3 inflammasome
activation. In addition, in vitro assays with neonatal rat cardiomyocytes further
confirmed that TLR4/MyD88/NF-kappaB signaling was significantly activated in the
inflammatory response of LPS-induced cardiomyocytes, via activation of the NLRP3
inflammasome. Inhibition of TLR4/MyD88/NF-kappaB signaling resulted in increased
survival of cardiomyocytes mainly by reducing the release of inflammatory
cytokines and decreasing NLRP3 inflammasome activation. CONCLUSIONS:
TLR4/MyD88/NF-kappaB signaling participates in the inflammatory response of the
myocardium after CME, activating the NLRP3 inflammasome, promoting the
inflammatory cascade, and aggravating myocardial injury. Blocking TLR4/MyD88/NF
kappaB signaling may help reduce myocardial injury and improve cardiac function
after CME.
PMID- 29940586
TI - Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and
Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of
Height by Combined Hormonal Therapies.
AB - BACKGROUND: Biologicals targeting the interleukin (IL)-1beta or IL-6 pathway are
becoming prime choices for the treatment of children with systemic juvenile
idiopathic arthritis (sJIA). Up to 1 in 3 sJIA children receiving such treatment
continues to have inflammatory activity and to require supra-physiological
glucocorticoid doses which may reduce growth velocity for years and may lead to
an extremely short stature for age, if not for life. Currently, there is no long
term proposal to normalize the adult height of these children with sJIA. METHODS
AND RESULTS: We present long-term (up to 10 years), proof-of-concept evidence
that the adult stature and adipose body composition of short sJIA children can be
normalized with a hormonal combination strategy: (i) pubertal onset is postponed
with a gonadotropin-releasing hormone analog (triptorelin) until a minimum height
is reached, or until prepubertal growth is exhausted, and (ii) height gain is
promoted with growth hormone (~50 MUg/kg/day), once inflammation is under control
and high glucocorticoid doses are no longer needed. The latter treatment takes
advantage of the window of relative glucocorticoid deficiency, which is known to
open after prolonged glucocorticoid administration, and to be uniquely favorable
to height gain. CONCLUSION: A long-term combination of biological and hormonal
treatments for short sJIA children can be guided by a simple concept that
involves (i) postponement of pubertal development and (ii) growth-promoting
therapy after the episodes of major inflammation and high-dose glucocorticoid
treatment. Limited long-term experience in short sJIA children suggests that this
strategy leads consistently - albeit late - to a normal adult stature.
PMID- 29940585
TI - Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of
'Trigger' and 'Substrate' Differences.
AB - BACKGROUND/AIMS: Recent research has improved our understanding of the pulmonary
vein and surrounding left atrial (LA-PV) junction and the left atrial appendage
(LAA), which are considered the 'trigger' and 'substrate' in the development of
atrial fibrillation (AF), respectively. Herein, with the aim of identifying the
underlying potential genetic mechanisms, we compared differences in gene
expression between LA-PV junction and LAA specimens via bioinformatic analysis.
METHODS: Microarray data of AF (GSE41177) were downloaded from the Gene
Expression Omnibus database. In addition, linear models for microarray data limma
powers differential expression analyses and weighted correlation network analysis
(WGCNA) were applied. RESULTS: From the differential expression analyses, 152
differentially expressed genes and hub genes, including LEP, FOS, EDN1, NMU,
CALB2, TAC1, and PPBP, were identified. Our analysis revealed that the maps of
extracellular matrix (ECM)-receptor interactions, PI3K-Akt and Wnt signaling
pathways, and ventricular cardiac muscle tissue morphogenesis were significantly
enriched. In addition, the WGCNA results showed high correlations between genes
and related genetic clusters to external clinical characteristics. Maps of the
ECM-receptor interactions, chemokine signaling pathways, and the cell cycle were
significantly enriched in the genes of corresponding modules and closely
associated with AF duration, left atrial diameter, and left ventricular ejection
function, respectively. Similarly, mapping of the TNF signaling pathway indicated
significant association with genetic traits of ischemic heart disease,
hypertension, and diabetes comorbidity. CONCLUSIONS: The ECM-receptor interaction
as a possible central node of comparison between LA-PV and LAA samples reflected
the special functional roles of 'triggers' and 'substrates' and may be closely
associated with AF duration. Furthermore, LEP, FOS, EDN1, NMU, CALB2, TAC1, and
PPBP genes may be implicated in the occurrence and maintenance of AF through
their interactions with each other.
PMID- 29940587
TI - A Prospective Cohort Study Showing No Association Between Serum Sclerostin Level
and Mortality in Maintenance Hemodialysis Patients.
AB - BACKGROUND/AIMS: Potential relationships between serum sclerostin levels and the
levels of bone metabolic markers in maintenance hemodialysis (MHD) patients have
yet to be evaluated. This study sought to determine whether serum sclerostin
levels are associated with mortality in MHD patients. METHODS: We measured serum
sclerostin levels in a Japanese MHD cohort, classified the patients into tertiles
according to these levels, and followed their course for a 42-month period.
RESULTS: The cohort consisted of 389 MHD patients and there were 75 deaths.
Kaplan-Meier analyses showed that the tertile of serum sclerostin was not
associated with mortality risk. Cox analyses showed that there were no
significant associations between serum sclerostin level and mortality.
CONCLUSION: Serum sclerostin level was not an independent predictor of mortality
in MHD patients after adjustment for several confounders. However, whether
clinical interventions to modulate serum sclerostin levels in MHD patients would
improve their survival remains to be determined.
PMID- 29940588
TI - Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART)
Study: Design and Baseline Characteristics (Report No. 1).
AB - PURPOSE: To describe the study design and characteristics at first visit of
participants in the longitudinal Scotopic Microperimetric Assessment of Rod
Function in Stargardt Disease (SMART) study. METHODS: Scotopic microperimetry
(sMP) was performed in one designated study eye in a subset of participants with
molecularly proven ABCA4-associated Stargardt disease (STGD1) enrolled in a
multicenter natural history study (ProgStar). Study visits were every 6 months
over a period ranging from 6 to 24 months, and also included fundus
autofluorescence (FAF). RESULTS: SMART enrolled 118 participants (118 eyes). At
the first visit of SMART, the mean sensitivity in mesopic microperimetry was
11.48 (+/-5.05; range 0.00-19.88) dB and in sMP 11.25 (+/-5.26; 0-19.25) dB. For
FAF, all eyes had a lesion of decreased autofluorescence (mean lesion size 3.62
[+/-3.48; 0.10-21.46] mm2), and a total of 76 eyes (65.5%) had a lesion of
definitely decreased autofluorescence with a mean lesion size of 3.46 (+/-3.60;
0.21-21.46) mm2. CONCLUSIONS: Rod function is impaired in STGD1 and can be
assessed by sMP. Testing rod function may serve as a potential outcome measure
for future clinical treatment trials. This is evaluated in the SMART study.
PMID- 29940589
TI - Multiple Primary Malignancies in Renal Transplant Recipients: a Single Centre
Retrospective Cohort Study.
AB - BACKGROUND/AIMS: Renal transplant recipients are exposed to immunosuppressive
treatment which may increase the risk for developing malignancies. Limited data
exists concerning the occurrence of multiple primary malignancies (MPM) in renal
transplant patients. METHODS: All the patients who received a renal allograft at
our institution from 1973 to 2017 were included in this investigation. Data from
patients with more MPM were obtained from the charts and medical records.
Malignancies were categorized as synchronous if the interval between occurrences
was less than or equal to 6 months and metachronous if the interval was more than
6 months. RESULTS: Out of the 1884 patients who received a renal allograft, 164
(8.7%) developed a malignant tumor. Twenty-two patients (13.4%; 6 females, 16
males) developed MPM, 7 synchronous (31.8%) and 15 metachronous types (68.2%).
The most common initial primary tumors were skin cancers (8) and kidney cancers
(3). Furthermore, skin cancers were the most common second primary malignancies
(9). Log-rank analysis revealed significantly better survival in the synchronous
group (113.3 months) than in the metachronous group (24.6 months) (p=0.04).
CONCLUSION: MPM are more frequent in renal transplant recipients than in the
general population. It is associated with a high mortality rate, especially in
the metachronous group. An increased awareness and frequent screening tests are
necessary when managing this condition.
PMID- 29940590
TI - Hemolysis and Glucose-6-Phosphate Dehydrogenase Deficiency-Related Neonatal
Hyperbilirubinemia.
AB - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common
enzyme deficiency affecting more than 300 million individuals worldwide. Extreme
neonatal hyperbilirubinemia, with its severe sequelae of bilirubin neurotoxicity
and the potential of death, is the most devastating manifestation of G6PD
deficiency. In a recent review of Favism, Luzzatto and Arese state that the
pathophysiology of jaundice in G6PD-deficient neonates is different from that of
favism, as there is little evidence of hemolysis in these infants. OBJECTIVES: To
explore the role of hemolysis in neonatal hyperbilirubinemia associated with G6PD
deficiency. METHODS: Previously published works including studies of endogenous
production of carbon monoxide (CO), an index of heme catabolism, in
hyperbilirubinemic G6PD-deficient neonates were reviewed to determine the role of
hemolysis in this condition. RESULTS: Three studies demonstrated that endogenous
CO production is elevated in G6PD-deficient neonates with extreme
hyperbilirubinemia. CONCLUSIONS: Hemolysis is an important pathogenetic factor in
G6PD deficiency-associated neonatal hyperbilirubinemia.
PMID- 29940591
TI - Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible
Electroporation for Pancreatic Cancer.
AB - BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an
advanced stage, resulting in extremely poor 5-year survival. Late diagnosis of
PDAC is mainly due to lack of a reliable method of early detection. Carbohydrate
antigen (CA) 19-9 is often used as a tumor biomarker in PDAC; however, the test
lacks sensitivity and specificity. Therefore, new sensitive and minimally
invasive diagnostic tools are required to detect pancreatic cancer. METHODS:
Here, we investigated circulating tumor DNA (ctDNA) which contained KRAS-mutated
as a potential diagnostic tool for PDAC patients who underwent irreversible
electroporation (IRE). We used droplet digital polymerase chain reaction (ddPCR)
to detect the expression of KRAS-mutated genes in plasma samples of 65 PDAC
patients who underwent IRE. RESULTS: In these 65 cases, ctDNA was detected in 20
(29.2%) samples. The median overall survival (OS) was 11.4 months with ctDNA+
patients and 14.3 months for ctDNA- patients. ctDNA+ patients had a obviously
poorer prognosis associated to overall survival (P < 0.001). CONCLUSION: Our
results suggested that the existence of ctDNA was a predictor of survival for
PDAC patients. Therefore, ctDNA may be a new sensitive biomarker for monitoring
treatment outcome in PDAC.
PMID- 29940592
TI - Ventilation Parameters under Adaptive Servo Ventilation: A Comparison on Behalf
of CSA-Pattern, BNP/NT-pro-BNP, and Ejection Fraction.
AB - BACKGROUND: The SERVE-HF study has raised questions concerning the higher
mortality under adaptive servoventilation. The ventilatory mode was discussed as
a possible aggravating factor. OBJECTIVES: We wondered if the data recorded by
the adaptive servo-ventilation (ASV)-devices in heart failure patients with CSA
CSR +/- OSA are different in terms of respiratory parameters and therapeutic
pressures compared to patients with CPAP-resistant/emergent-CSA with normal
BNP/NT-pro-BNP. METHODS: Patients were included, if ASV had normalized
respiratory disturbance index in the first night of application and after at
least 6 weeks. ASV-device data were analyzed in terms of respiratory rate (RR),
min ventilation (MV), endexpiratory (EEP), peak inspiratory pressure (Ppeak) and
median pressure. RESULTS: Compared to CPAP-resistant/emergent-CSA with normal
BNP/NT-pro-BNP (n = 25), CSA-CSR- (n = 13) CSA-CSR+OSA-patients (n = 32) with
elevated BNP/NT-pro-BNP had higher RR (p < 0.01) in the first night of ASV
therapy and during follow-up (15.3 +/- 1.3 vs. 17.3 +/- 2.4/min) with similar MV
(6.5 +/- 1.3 vs. 6.6 +/- 1.3 L), resulting in significantly lower tidal volumes.
EEP (5.6 +/- 1.1 vs. 5.5 +/- 1.1 hPa), Pmedian and Ppeak (9.8 +/- 1.5 vs. 9.7 +/-
1.2 hPa) were comparable. Ventilatory parameters were not different between LVEF
< 40, 40-49, and >=50%, neither within the whole group nor the group of CSA-CSR
+/- OSA and heart failure. CONCLUSION: Patients with heart failure and CSA-CSR +/
OSA have higher RRs but similar MV under ASV-therapy than patients with CSA and
normal BNP. This indicates higher dead space ventilation. EF was not found to
have an influence on the ventilatory parameters.
PMID- 29940593
TI - Office Visit: Kidney Transplantation of a Dreamer.
AB - This editorial describes a patient who was cared for by the author. The patient
developed end-stage kidney disease in the United States at the age of 17 but was
denied kidney transplantation due to lack of insurance because of her immigration
status. With the enactment of the Deferred Action for Childhood Arrivals (DACA)
program, the patient was able to obtain a job and health insurance. The patient
then received a kidney transplant when she was 27 years, after undergoing
peritoneal dialysis for 10 years. The editorial describes how the DACA program
improves the care of undocumented immigrants to the United States who are
affected by kidney disease. While many might consider kidney transplantation to
be available to all individuals in the United States, this is not the case.
Individuals who are not US citizens are for practical purposes unable to undergo
transplantation in almost all states because of their inability to obtain health
insurance. This editorial describes the history of one of my patients, and the
profound impact that the DACA program (Dreamer Act) had on her care. This
legislation is currently under review for continued approval in the United States
legislature. I am happy to see my patient in clinic today for medical care
following successful kidney transplantation.
PMID- 29940594
TI - Effect of Home Blood Pressure Monitoring on Patient's Awareness and Goal
Attainment Under Antihypertensive Therapy: The Factors Influencing Results in
Anti-HypertenSive Treatment (FIRST) Study.
AB - BACKGROUND/AIMS: Despite availability of a broad spectrum of blood pressure (BP)
lowering drugs many hypertensive patients do not attain BP goals. We aimed to
evaluate the influence of home blood pressure monitoring (HBPM) on patient's
awareness and attainment of BP goals under antihypertensive treatment with
irbesartan alone or in combination with hydro-chlorothiazide. METHODS: In total,
1,268 patients with arterial hypertension were enrolled in the Factors
Influencing Results in anti-hypertenSive Treatment (FIRST) study by 348 general
practitioners and internal medicine specialists across Switzerland. Patients
selected for HBPM received detailed information and training on BP self
management. The study endpoints included patient's awareness and attainment of BP
goals, and the efficacy and tolerability of antihypertensive treatment at 3
months. RESULTS: Overall, the mean age was 61+/-13 years and 616 (49%) were
women. The mean systolic/diastolic BP was 161+/-17/96+/-11 mmHg, and 239 (19%)
patients had diabetes mellitus. 758 (60%) patients were instructed to use HBPM.
Both the proportion of patients aware of their BP goals (81% vs. 70%; p< 0.001)
and the percentage of patients reaching their BP goal (64% vs. 57%; p=0.028) were
higher in those with vs. without HBPM. The mean reduction in systolic/diastolic
BP was 23.8/13.2 mmHg. Only 35 (3.0%) patients discontinued antihypertensive
therapy. CONCLUSION: In a large Swiss cohort of patients with arterial
hypertension, information and training on BP self-measurement and direct
involvement of patients by using HBPM led to improvement in BP control. Treatment
with irbesartan alone or in combination with hydrochlorothiazide was well
tolerated and markedly reduced BP.
PMID- 29940595
TI - Assessment of Peritoneal Membrane Arteriolar Structure in Conjunction with
Traditional Cardiovascular System Evaluation in Chronic Kidney Disease (CKD)
Stage 5 Patients.
AB - BACKGROUND/AIMS: Cardiovascular complications are responsible for increased
mortality and morbidity in chronic kidney disease (CKD) patients. Functional and
structural changes of peritoneal membrane are reported in CKD patients both on
conservative treatment and on renal replacement therapy (RRT). The aim of the
study was to assess the structure of peritoneal membrane small arteries
(precapillary arterioles) in diabetic and non-diabetic CKD stage 5 patients
before initiation of peritoneal dialysis (PD) and evaluate its relationship with
heart and large arteries abnormalities and with selected biochemical parameters.
METHODS: Evaluation of 42 CKD stage 5 patients before starting PD. Diabetic
(n=26) and non-diabetic (n=16) patients were compared. Peritoneal membrane
samples were taken during Tenckhoff catheter insertion. Histopathological
evaluation of peritoneal precapillary arterioles (arteriolar evaluation) with
measurement of wall thickness (WT) and calculation of lumen/vessel (L/V) ratio
was performed in each patients. Echocardiography, intima media thickness (IMT),
pulse wave velocity (PWV), ambulatory blood pressure monitoring (ABPM) and
biochemical parameters assessment: serum albumin (SA), total cholesterol (TCH),
hemoglobin (Hgb), parathormone (PTH), serum calcium (Ca), serum phosphorus (P),
transferrin saturation (TSAT%), C-reactive protein (CRP) were performed in each
participant. RESULTS: There were no statistically significant differences in
peritoneal membrane arteriolar indices - wall thickness (WT) and L/V ratio
between investigated groups. There was statistically significant higher PWV value
in diabetic patients. There were no statistically significant differences in
echocardiographic indices, IMT, laboratory data in analyzed groups. There were
some linear correlations between: PWV vs IMT (R=0,84; p=0,0006); PWV vs PP
(R=0,58; p=0,03) in non-diabetic and linear correlation between: PWV vs age
(R=0,75; p=0,02); WT vs DP (R=-0,93; p=0,001); WT vs DBP ( R=0,64; p=0,04) in
diabetic group. CONCLUSION: Peritoneal membrane arteriolar damage seems to be an
integrated part of cardiovascular system damage in CKD stage 5 patients.
PMID- 29940596
TI - The Relationship between White Matter and Reading Acquisition, Refinement and
Maintenance.
AB - : Reading requires efficient communication between brain regions that are
situated all over the cortex. These brain areas are structurally connected by
white-matter pathways that develop over the period of reading acquisition. Here,
we conducted a cross-sectional study to assess the relationship between white
matter tracts and reading performance across the lifespan. METHODS: Behavioral
(reading performance) and neuroimaging (diffusion tensor imaging [DTI]) data were
collected from participants aged 3-21 years as a part of the multi-site project
called the pediatric imaging neurocognition genetics study. DTI measures
(fractional anisotropy [FA], mean diffusivity, radial diffusivity and axial
diffusivity) of bilateral dorsal tracts (arcuate fasciculus, superior
longitudinal fasciculus, and posterior superior longitudinal fasciculus) and
ventral tracts (uncinate fasciculus, inferior fronto-occipital fasciculus, and
inferior longitudinal fasciculus) were extracted. Reading performance was
calculated as the number of items correctly read (words for older children and
letters in the case of young children). Correlational and regression analyses
were conducted between the DTI measures and reading scores. RESULTS: During the
early stages of reading acquisition (ages 3-6), the dorsal tracts were positively
related to reading performance (as FA goes up, reading performance goes up). For
ages 6-10, the dorsal tracts remain positively associated with reading
performance and a relationship between ventral tracts and reading performance
emerges. From the age of 10 onwards, the dorsal tracts no longer correlate with
reading performance, and a brain-behavior relationship in the right ventral
tracts begins to shift, whereby higher FA is associated with lower reading
performance. In addition to the involvement of left hemispheric tracts, this
study revealed the initial engagement of right hemispheric tracts during the
early stages of reading acquisition. CONCLUSION: We discuss these different
associations of white-matter tracts with reading during development in the
context of the biological processes model of myelination and pruning.
PMID- 29940598
TI - The So-Called "Protective Effect" of Preeclampsia on Perinatal Brain Damage.
PMID- 29940597
TI - Farnesoid X Receptor (FXR) Interacts with Camp Response Element Binding Protein
(CREB) to Modulate Glucagon-Like Peptide-1 (7-36) Amide (GLP-1) Secretion by
Intestinal L Cell.
AB - BACKGROUND/AIMS: Type II diabetes is a complex, chronic, and progressive disease.
Glucagon-like peptide-1 (7-6) amide (GLP-1) is a gut hormone released from the L
cells which stimulates insulin secretion, and promotes insulin gene expression
and beta-cell growth and differentiation. Elevated levels of hormone secreted by
L cells are an important reason for diabetes improvement. GLP-1 secretion has
been reported to be regulated by farnesoid X receptor (FXR), a transcriptional
sensor for bile acids which also acts on glucose metabolism. Herein, we attempted
to evaluate the effect of FXR on GLP-1 secretion in mouse enteroendocrine L cell
lines, STC-1 and GLUTag, and to investigate the underlying mechanism. METHODS:
ELISA and Western blot assays were employed to examine the levels of GLP-1 and
FXR, and the effect of FXR on GLP-1 secretion; online database, including BioGRID
and KEGG were used to identify the potential interactions between FXR and
proteins and involved pathways; GST pull-down and Co-Immunoprecipitation (Co-IP)
assays were performed to validate FXR-CREB interaction; Luciferase reporter gene
assays were used for CREB transcriptional activity determination. RESULTS: FXR
inversely regulated GLP-1 secretion in the mouse enteroendocrine L cell lines,
GLUTag and STC-1. A total of 24 nonredundant human proteins were shown to be
related to FXR by BioGRID; KEGG pathway analysis showed that FXR was related to
glucagon signaling pathway, particularly with the transcriptional activators
CREB, PGC1alpha, Sirt1 and CBP. CREB could positively regulate GLP-1 secretion in
GLUTag and STC-1 cells. FXR combined with CREB to inhibit its transcriptional
activity, thus inhibiting proprotein convertase subtilisin/ kexin type 1 (PCSK1)
protein level and GLP-1 secretion. CONCLUSION: In the present study, we
demonstrated a negative regulation of GLP-1 secretion by FXR in L cell lines,
GLUTag and STC-1; FXR exerts its function in L cells through interacting with
CREB, a crucial transcriptional regulator of cAMP-CREB signaling pathway, to
inhibit its transcriptional activity. Targeting FXR to rescue GLP-1 secretion may
be a promising strategy for type II diabetes.
PMID- 29940599
TI - Association of Nesfatin-1, Acylated Ghrelin and Cortisol with Scores of
Compulsion, Food Addiction, and Binge Eating in Adults with Normal Weight and
with Obesity.
AB - BACKGROUND/AIMS: The alterations of eating behavior are insufficiently recognized
in the clinical attention of adults with obesity. The objective of this study was
to examine the characteristics of overeating behavior and its association with
depression, perceived stress, acylated ghrelin, nestafin-1, and cortisol.
METHODS: This cross-sectional comparative study included 80 participants with
obesity and 50 with normal weight. The volunteers completed questionnaires to
evaluate symptoms of food addiction (FA), obsessive compulsive, binge eating
(BE), depression, and perceived stress. We measured glucose, lipids, acylated
ghrelin, nesfatin-1, and insulin in a fasting blood sample as well as urine
cortisol. We compared groups with students t test, and analysis of variance, and
tested associations by logistic and multiple regression. RESULTS: By multiple
regression, the BE total score was positively associated with the FA (p < 0.0001)
and depression total score (p < 0.0001). By logistic regression, the positive
score of FA was associated with ghrelin (p < 0.02). The perceived stress total
score was associated negatively with cortisol (p < 0.0006). CONCLUSION: The BE
and FA are strongly associated in agreement with the concept that both conditions
have overlapping features. Depressive symptoms are associated with symptoms of
disordered eating -behavior. FA positive score was associated with ghrelin. BE
total score was associated with nesfatin-1.
PMID- 29940600
TI - Neonatal Phototherapy: A Novel Therapy to Prevent Allergic Skin Disease for At
Least 5 Years.
AB - BACKGROUND: Preventing the development of allergic skin disease in children is
the best way to treat the disease. OBJECTIVES: Ultraviolet (UV)-free blue light
phototherapy has been reported to treat atopic eczema. We evaluated the effect of
neonatal phototherapy on allergic skin disease in children. METHODS: We randomly
recruited 117,041 children from an insurance research database. Those with
neonatal jaundice and receiving neonatal phototherapy were classified as the
icteric-phototherapy group (n = 4,744), those with neonatal jaundice and not
receiving phototherapy were classified as the icteric-non-phototherapy group (n =
5,003), and those without jaundice were classified as the non-icteric group (n =
107,294). We reviewed claims from birth to age 5 years. The prevalence of atopic
dermatitis (AD), clinical visit times, and topical prescriptions for allergic
skin disease at different ages were compared among groups. RESULTS: AD prevalence
was lower in the icteric-phototherapy group than in the icteric-non-phototherapy
group. Moreover, clinical visit times for allergic skin disease were lower at age
1-4 years, and topical agent prescription for allergic skin disease were lower at
age 1-5 years, in the icteric-phototherapy group than in the icteric-non
phototherapy group. The decreased use of topical agents could reach 64.29%. The 5
year complications of skin disease and cancer in the phototherapy group were not
higher. CONCLUSIONS: To our knowledge, this is the first study to report on the
effect of UV-free blue light therapy on allergic skin disease in newborns. Blue
light therapy in newborns may be a novel method to efficiently prevent allergic
skin disease for at least 5 years.
PMID- 29940602
TI - Validating the Syndemic Threat Surrounding Sexual Minority Men's Health in a
Population-Based Study With National Registry Linkage and a Heterosexual
Comparison.
AB - BACKGROUND: Research on the syndemic health threats facing sexual minority men
suggests that the elevated risk of HIV among this population co-occurs with other
psychosocial health disparities. This study aimed to conduct a population-based
examination of clinically assessed syndemic predictors of HIV infection among gay
and bisexual, compared with heterosexual, men. SETTING AND METHODS: The sample
comprised adult men in the Stockholm Public Health Cohort. A total of 29,328
(91.9%) self-identified as heterosexual, 535 (1.7%) as gay, and 396 (1.2%) as
bisexual. We linked survey responses to national health registry data. RESULTS:
Gay men had vastly elevated risk of HIV infection (>150 times) compared with
heterosexuals. Gay men also had an elevated risk of depression, suicidality, and
violent assaults compared with heterosexuals. Bisexual men had 16 times higher
risk of being HIV-positive than heterosexual men. The number of psychosocial
syndemic conditions was significantly associated with HIV infection among gay men
(adjusted odds ratio [AOR] = 1.67; 95% confidence interval [95% CI]: 1.18 to
2.36), but not among bisexual and heterosexual men (AOR = 0.51; 95% CI: 0.07 to
3.59; AOR = 1.92; 95% CI: 0.96 to 3.84). Among gay men, the association between
co-occurring syndemic conditions and odds of HIV infection was synergistic (ie,
more than additive). CONCLUSIONS: This study confirms emerging evidence of the
syndemic health threats affecting sexual minority men, finds stronger evidence
for syndemics among gay compared with bisexual men, and suggests the need for HIV
prevention interventions that comprehensively address the co-occurring, and
synergistically perpetuating, disparities affecting this population.
PMID- 29940601
TI - Leveraging Phylogenetics to Understand HIV Transmission and Partner Notification
Networks.
AB - BACKGROUND: Partner notification is an important component of public health test
and treat interventions. To enhance this essential function, we assessed the
potential for molecular methods to supplement routine partner notification and
corroborate HIV networks. METHODS: All persons diagnosed with HIV infection in
Wake County, NC, during 2012-2013 and their disclosed sexual partners were
included in a sexual network. A data set containing HIV-1 pol sequences collected
in NC during 1997-2014 from 15,246 persons was matched to HIV-positive persons in
the network and used to identify putative transmission clusters. Both networks
were compared. RESULTS: The partner notification network comprised 280 index
cases and 383 sexual partners and high-risk social contacts (n = 131 HIV
positive). Of the 411 HIV-positive persons in the partner notification network,
181 (44%) did not match to a HIV sequence, 61 (15%) had sequences but were not
identified in a transmission cluster, and 169 (41%) were identified in a
transmission cluster. More than half (59%) of transmission clusters bridged
sexual network partnerships that were not recognized in the partner notification;
most of these clusters were dominated by men who have sex with men. CONCLUSIONS:
Partner notification and HIV sequence analysis provide complementary
representations of the existent partnerships underlying the HIV transmission
network. The partner notification network components were bridged by transmission
clusters, particularly among components dominated by men who have sex with men.
Supplementing the partner notification network with phylogenetic data highlighted
avenues for intervention.
PMID- 29940603
TI - HIV Infection Is Associated With Abnormal Bone Microarchitecture: Measurement of
Trabecular Bone Score in the Women's Interagency HIV Study.
AB - OBJECTIVES: We compared skeletal microarchitecture using trabecular bone score
(TBS) and evaluated relationships between change in TBS and lumbar spine (LS)
bone mineral density (BMD) in women with and without HIV. METHODS: Dual-energy X
ray absorptiometry was performed on 319 women with HIV and 118 without HIV in the
Women's Interagency HIV Study at baseline and 2 and 5 years, to measure regional
BMD and lean and fat mass. TBS was extracted from LS dual-energy X-ray
absorptiometry images and examined continuously and categorically [normal
(>=1.35), intermediate (1.20-1.35), or degraded (<=1.20) microarchitecture].
Pearson correlation and linear regression examined associations of TBS with
regional BMD at baseline and over time. RESULTS: Women with HIV were older (43
vs. 37 years), more likely to be postmenopausal (27% vs. 4%), have lower baseline
total fat mass, trunk fat, and leg fat than uninfected women, degraded
microarchitecture (27% vs. 9%, P = 0.001), and lower baseline mean TBS (1.3 +/-
0.1 vs. 1.4 +/- 0.1, P < 0.001). After adjusting for age, race, menopause status,
and body mass index, TBS remained lower in women with HIV (P < 0.0001). Annual
change in TBS correlated with LS BMD change among women with HIV (r = 0.36, P <
0.0001) and without HIV (r = 0.26, P = 0.02); however, mean % annual TBS change
did not differ by HIV status (-1.0%/yr +/- 2.9% for HIV+ vs. -0.8%/yr +/- 1.7%
for HIV-, P = 0.42). CONCLUSIONS: Women with HIV have worse bone
microarchitecture than uninfected women, but annual percent change in LS BMD or
TBS was similar. Use of TBS as an adjunct to BMD to improve prediction of
fragility fractures in women with HIV merits further study.
PMID- 29940604
TI - Outcomes and Complications Following Laminectomy Alone for Thoracic Myelopathy
due to Ossified Ligamentum Flavum: A Systematic Review and Meta-Analysis.
AB - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Examine the
functional outcomes and complications following laminectomy for thoracic
myelopathy due to ossification of the ligamentum flavum (OLF). SUMMARY OF
BACKGROUND DATA: OLF is a rare condition that can cause thoracic myelopathy.
Laminectomy is a procedure that can be performed to decompress the spinal cord in
patients with thoracic myelopathy due to OLF. Few studies have examined
postoperative outcomes and complications following laminectomy for thoracic
myelopathy secondary to OLF. METHODS: A systematic review and meta-analysis was
performed. Literature search yielded six studies that met our selection criteria.
Study characteristics and baseline patient demographics were extracted from each
study. Primary outcomes included pre- and postoperative Japanese Orthopedic
Association (JOA) scores and perioperative complications including dural tears,
cerebrospinal fluid (CSF) leaks, neurological deficits, surgical site infections,
and other complications. We calculated pooled proportion estimates for JOA scores
and complications using a random effects model. RESULTS: A total of 137 patients
were included. The pooled pre- and postoperative JOA scores were 5.08 (95%
confidence interval [CI], 2.70-7.47; I = 98%) and 8.29 (95% CI, 7.73-8.85; I =
18%), respectively, with a mean improvement of +3.03 points (95% CI, 1.08-4.98; I
= 88%). Pooled proportion estimates for dural tears, CSF leaks, infections, and
early neurological deficits were 18.4% (95% CI, 12.6-26.1; I = 0%), 12.1% (95%
CI, 6.6-21.2; I = 0%), 5.8% (95% CI, 2.1-15.4; I = 0%), and 5.7% (95% CI, 2.2
14.3; I = 0%), respectively. CONCLUSION: Thoracic myelopathy secondary to OLF can
be treated with laminectomy. However, despite some improvement in JOA score,
functional status remains poor postoperatively. Perioperative complications are
common, with dural tears and CSF leaks occurring most frequently. OLF is an
uncommon condition and more research is needed to better understand how we can
improve the outcomes of laminectomy alone for the treatment of thoracic
myelopathy due to OLF. LEVEL OF EVIDENCE: 3.
PMID- 29940606
TI - Microglia morphology in the physiological and diseased brain - from fixed tissue
to in vivo conditions.
AB - First mentioned almost 100 years ago, neuroresearch has linked microglia to the
initiation and/or maintenance of most central nervous system pathologies. Since
their discovery, we learned that the microglia immune status is often correlated
directly to their morphology. However, only recently, have we realized that, in
vivo microglia are extremely dynamic cells capable to respond within minutes.
Therefore, the name "resting" microglia is replaced slowly with surveilling
microglia. Even more recent, it has been shown that microglia change their
morphology and/or immune status depending on the way the tissue is obtained,
processed and imaged, making labeling microglia, based on their morphology alone,
as active or surveying even more difficult. All these observations correlated
with a better understanding of cellular and subcellular process that microglia
undergo in pathological conditions, could have profound implications on the time
window and/or targets used to ensure the best outcome, when treating brain
disease.
PMID- 29940607
TI - Clinicopathological significance and prognostic value of myoinvasive patterns in
endometrial endometrioid carcinoma.
AB - Endometrioid endometrial carcinoma has an overall good prognosis. However,
variable five-year survival rates (92%-42%) have been reported in FIGO stage I,
suggesting the involvement of other factors related to tumor biological behavior.
These may be related to the role played by epithelial-mesenchymal transition
(EMT) and cancer stem cells in endometrial carcinogenesis. In this context, our
review highlights the prognostic significance of several types of myoinvasion in
low grade, low stage endometrioid endometrial carcinoma, as a reflection of these
molecular changes at the invasive front. According to recently introduced
myoinvasive patterns, the diffusely infiltrating and microcystic, elongated, and
fragmented (MELF) patterns show loss of hormone receptors, along with EMT and
high expression of cancer stem cell markers, being associated with a poor
prognosis. Additionally, MELF pattern exhibits a high incidence of lymphovascular
invasion and lymph node metastases. Conversely, the broad front pattern has a
good prognosis and a low expression of EMT and stem cells markers. Similarly, the
adenomyosis (AM)-like and adenoma malignum patterns of invasion are associated to
a favorable prognosis, but nevertheless, they raise diagnostic challenges. AM
like pattern must be differentiated from carcinoma invasion of AM foci, while
adenoma malignum pattern creates difficulties in appreciating the depth of
myoinvasion and requires differential diagnosis with other conditions. Another
pattern expecting its validation and prognostic significance value is the nodular
fasciitis-like stroma and large cystic growth pattern. In practice, the knowledge
of these patterns of myoinvasion may be valuable for the correct assessment of
stage, may improve prognosis evaluation and may help identify molecules for
future targeted therapies.
PMID- 29940605
TI - Propofol Promotes Ankle Fracture Healing in Children by Inhibiting Inflammatory
Response.
AB - BACKGROUND The present study aimed to investigate the potential effects of
propofol on ankle fracture healing in children and the underlying molecular
mechanisms. MATERIAL AND METHODS We first detected the levels of inflammatory
cytokines from peripheral blood in children with or without ankle fracture using
quantitative real-time polymerase chain reaction (qRT-PCR) and ELISA assay. Then,
effects of propofol on inflammatory response in MG-63 cells were investigated. MG
63 cells were pre-treated with or without propofol and then stimulated with 1 MUM
bradykinin (BK). The productions of cytokines from MG-63 cells were determined by
using qRT-PCR and Western blot assay. The expression levels of p-p38, NF-kappaB p
p65, NLRP3, ASC, caspase-1, and COX-2 were measured by Western blot and/or qRT
PCR. RESULTS The results showed that, compared with the healthy children, the
levels of tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta, and IL-6
were significantly up-regulated in children with fractured ankles. No
cytotoxicity was observed in MG-63 cells after propofol treatment. BK treatment
significantly enhanced TNF-alpha, IL-1beta, and IL-6 expression levels, and these
enhancements were reduced by propofol treatment in a dose-dependent manner.
Moreover, BK-induced up-regulation of p-p38, NF-kappaB p-p65, NLRP3, ASC, caspase
1, and COX-2 was dose-dependently down-regulated by propofol treatment.
CONCLUSIONS Propofol prevents inflammation in MG-63 cells by regulating p38MAPK
NF-kappaB pathway, NLRP3 inflammasome, and COX-2 expression. Our findings
indicate the benefits of propofol in fracture healing, and provide a more
theoretical basis for the clinical treatment of fractures.
PMID- 29940608
TI - The role of tumor microenvironment in development and progression of malignant
melanomas - a systematic review.
AB - To reveal the particular aspects of the tumor microenvironment of malignant
melanomas, a systematic review including 34 representative papers was performed.
The review took into account the aspects related the Wnt/beta-catenin pathway
related epithelial-mesenchymal transition (EMT) versus mesenchymal-epithelial
transition (MET) of keratinocytes, fibroblasts and melanoma cells, as possible
tools for understanding genesis and evolution of malignant melanoma. The possible
reversible features of EMT and the role of tumor microenvironment in the
metastatic process were also analyzed. A particular issue was related on the
cancer stem cells that include melanocyte stem cells (McSCs) and multipotent
mesenchymal stem/stromal cells (MSCs). As the McSCs embryological development in
mouse is not similar to human development, the role of stem cells in genesis and
development of human melanoma should be proved in human melanoma cells only. For
further development of targeted therapy, a better understanding of
melanomagenesis pathways and its microenvironment particularities is necessary.
PMID- 29940609
TI - Immunohistochemistry predictive markers for primary colorectal cancer tumors:
where are we and where are we going?
AB - The aim of our study is to highlight and organize the recently published
immunohistochemistry (IHC) predictive biomarkers of primary colorectal cancers
(CRCs) that could lead to practical implementation. We reviewed articles that
examined CRC samples with significant statistic correlation between the IHC
marker expression and disease progression over time, relationships with the
available clinical features and those who detect the prognosis of drug effects.
Our analysis showed that nine markers could correlate with medical treatment
response of CRCs in different stages. When using better overall survival (OS) and
better disease-free survival (DFS) as a grouping factor, there were 14 markers
that could be used in assessing CRC prognosis. By using poor prognostic for the
OS and the DFS as a grouping factor, we found 43 markers. Subgroup analysis was
also performed based on the 32 markers recently confirmed to predict metastasis
evolution or the recurrence risks. Venous invasion could be predictable for
tumors, statistically significant metastasis susceptibility was observed for
markers and also the capacity to evaluate recurrence. CRCs integrate a variety of
localizations and there are proofs that distinguish the sites of tumors. The
studies reporting data specifically for rectal cancer separating it from colon
cancer contained seven IHC markers. In order to be able to implement a predictive
biomarker in clinical practice, it must comply with certain criteria as clinical
value and analytical proof. Unique biological signature of CRC can be
distinguished by identifying biomarkers expression. Several markers have shown
potential, but the majority still need to render clinical utility.
PMID- 29940610
TI - The prostatic cellular and molecular kaleidoscope. Starting points for
carcinogenesis.
AB - The prostate cancer is a heterogeneous disorder concealing different phenotypical
and functional subtypes of cancer cells. This heterogeneity mirrors the normal
prostate cell lineages whose alterations represent the starting points of the
carcinogenesis mechanism. The histological structure of the prostate comprises
two main types of cells: epithelial and stromal, with a stromal to epithelial
ratio of 2:1. The prostate acini are lined by a contiguous layer composed of four
different subtypes of epithelial cells: secretory luminal, basal, neuroendocrine,
and transit-amplifying. The epithelial component is enclosed in a stromal tissue,
consisting of several types of cells: smooth muscle cells (the most numerous cell
type), fibroblasts, and myofibroblasts. Despite their quite similar morphological
appearance in light microscopy, the molecular markers expressed by the normal
epithelial and stromal prostatic components, as well as the stem cells show that
the prostatic cells are not equal. Numerous efforts have been made to identify
the profile of prostate stem cells, and their role in cellular turnover and
morphogenesis of the prostatic tissue, by using experimental and/or human
studies. Consequently, several hypotheses regarding the location and the
phenotype of these cells were formulated and tested, mainly in animal models. The
molecular mapping of normal human prostate tissue might be the key for unlocking
the intricate mechanisms of prostate carcinogenesis. Within this context, the
prostatic cancer stem cells are thought to play an important role in tumor
initiation, progression, recurrence and also therapy resistance. The cancerous
phenotype of a stem cell can be reached via multiple genetic trajectories and
epigenetic alterations, resulting in different subclonal populations of cancer
stem cells, thus explaining the heterogeneity of the prostatic neoplasia. Future
efforts should be directed towards better understanding of the relationship and
interactions between these cancer stem cells subpopulations, their
microenvironments, and also towards characterizing the signaling pathways and
molecules involved in the regulation of prostatic cancer stem cells. The results
of these studies could offer a different, more comprehensible perspective for a
new, molecular classification of prostate cancer, overlapping the existing
histological one.
PMID- 29940611
TI - Mg-Zn alloys, most suitable for biomedical applications.
AB - In this review are highlighted the corrosion and biocompatibility of
biodegradable Mg alloys for their use in orthopedic applications. It was revealed
that mixing with alloying elements, such as Mn and Zn, provides improved
corrosion resistance to Mg alloys; this pursuit is built on the fact that Mg and
its alloys are degradable through their time in the human body. Furthermore, Mg
alloys afford a characteristic profile that is very close or even almost
identical to that of human bone. Minimizing the rate of corrosion of Mg is the
most adequate method, because a low corrosion rate of an Mg implant involves a
decrease in the extent of hydrogen evolution and alkalization, which allow the
human body to gradually absorb or consume the corrosion products.
PMID- 29940612
TI - The role of skin and muscle biopsy in the diagnosis of main connective tissue
diseases.
AB - Systemic involvement in autoimmune diseases is often unclear and organ changes
are confounding, thus making it difficult to have an early accurate diagnosis. In
those situations, both clinical and paraclinical findings might orientate the
diagnosis, but only histological or immunohistochemistry changes might be
accurate enough. The skin histological changes are relevant and sometimes might
have a tremendous role in the accurate diagnosis of autoimmune rheumatic
diseases, due to the correlation with the clinical systemic manifestations of the
diseases and through the accessibility of biopsy. In the same time, muscle biopsy
can provide important support for physicians improving diagnosis and optimizing
management of connective tissue diseases.
PMID- 29940613
TI - Correlations between morphological changes induced by curcumin and its biological
activities.
AB - Curcumin is a phytochemical polyphenol extracted from turmeric rhizome, with
multiple biological activities, intensively studied in various therapeutic areas.
Its effects covers a wide range of specialties, from the neuroprotective to the
antimetastatic properties, influencing pathologies from cardiovascular, neuronal
and oncological fields, as a part of its broad spectrum of action. These effects
are explained by antioxidant, anti-inflammatory and anticarcinogenic simultaneous
roles of curcumin and its derivatives. In this review, we selected the
information about morphological evidences correlated with the biological effects
on the following organ systems: the central nervous system (including
neurological pathology, such as Parkinson's and Alzheimer's disease), the
cardiovascular system (including disorders like atherosclerosis, endothelial
dysfunction and drug-induced myotoxicity), multiple forms of cancer, and
metabolic syndromes including diabetes. The central point of this review was to
target a variety of morphological changes at microscopic level induced by
curcumin, using different microscopy techniques.
PMID- 29940614
TI - Hyaluronic acid-based scaffolds for tissue engineering.
AB - Hyaluronic acid (HA) is a natural glycosaminoglycan found in the extracellular
matrix of most connective tissues. Due to its chemical structure, HA is a
hydrophilic polymer and it is characterized by a fast degradation rate. HA-based
scaffolds for tissue engineering are intensively studied due to their increased
biocompatibility, biodegradability and chemical modification. Depending on the
processing technique, scaffolds can be prepared in the form of hydrogels,
sponges, cryogels, and injectable hydrogels, all discussed in this review.
PMID- 29940615
TI - Sepsis and identification of reliable biomarkers for postoperative period
prognosis.
AB - Sepsis is currently defined as the presence of organ dysfunction occurring as the
result of a disturbed host response to a serious infection. Sepsis is one of the
most common diseases, which cause mortality and a considerable absorber of
healthcare resources. Despite progress in technology and improving knowledge of
pathophysiology, the disease mechanism is still poorly understood. At present,
diagnosis is based on non-specific physiological criteria and on the late
identification of the pathogen. For these reasons, the diagnosis may be
uncertain, treatment delayed or an immunomodulatory therapy cannot be
established. An early and reliable diagnosis is essential to achieve better
outcomes on disease progression. The host response to infection involves hundreds
of many mediators of which have been proposed as biomarkers. There is a need for
new diagnostic approaches for sepsis, new sepsis biomarkers that can aid in
diagnosis, therapeutic decision and monitoring of the response to therapy. The
differentiation of sepsis from non-infectious systemic inflammatory response
syndrome is difficult, and the search for a highly accurate biomarker of sepsis
has become one important objective of the medicine. The goal of our review is to
summarize the recent advances on the most commonly studied serum biomarkers,
evaluated in clinical and experimental studies, for early diagnosis of sepsis and
their informative value in diagnosis, prognosis, or response to therapy. In this
context, we have tracked the clinical utility of measuring serum biomarkers, such
as procalcitonin, pro- and anti-inflammatory cytokines, C-reactive protein,
leptin and their combinations. Currently, has not been identified an ideal
biomarker to aid in the diagnosis of sepsis. It is hoped that the discovery of
new serum markers, as well as their combinations, will serve for the diagnosis
and prognosis of sepsis.
PMID- 29940616
TI - A morpho-functional study using PEP/LVET ratio and global longitudinal strain in
patients with dilated cardiomyopathy.
AB - AIM: To assess left ventricular (LV) systolic function and morphology in patients
with severe dilated cardiomyopathy (DCM), using both conventional and a complex
technique, speckle-tracking echocardiography, and evaluate the correlation
between pre-ejection period and left ventricular ejection period (PEP/LVET)
ratio, global longitudinal strain (GLS), and severity of the condition. PATIENTS,
MATERIALS AND METHODS: Seventeen patients were enrolled after rigorous criteria.
Echocardiography was performed in conventional and speckle-tracking mode, in all
patients with DCM, in sinus rhythm. LV dimensions, volumes and ejection fraction
(LVEF) were measured. PEP/LVET ratio was obtained from apical 5-chamber axis and
was defined as the time between QRS onset and LV ejection reported to LV ejection
period. Speckle-tracking imaging was performed in offline mode and GLS was
obtained from parasternal 4-, 3-, 2-chamber apical view, by averaging
longitudinal peak systolic strain of all 17 LV-segments. RESULTS: New York Heart
Association (NYHA) functional class correlated significantly with LVEF (-0.82;
p=0.0006), PEP/LVET (0.86; p=0.001) or GLS (0.85; p=0.0002). Considerable
correlations were between mitral regurgitation (MR) severity and LVEF (-0.65;
p=0.01) or PEP/LVET (0.69; p=0.0059), but higher were between MR severity and GLS
(0.76; p=0.0018). Tricuspid regurgitation (TR) grading correlated statistically
with LVEF (-0.62; p=0.01), PEP/LVET and GLS (0.6; p=0.018; and 0.62; p=0.014,
respectively). As opposed to the parameters in conventional echocardiography, GLS
correlated with DCM etiology (p=0.0046) and with the gender (p=0.048).
CONCLUSIONS: This study demonstrates that, in patients with DCM, assessment of
cardiac dyssynchrony can be accurately accomplished by combining parameters in
conventional and in speckle-tracking echocardiography.
PMID- 29940617
TI - Vestibular sensory functional status of cochlear implanted ears versus non
implanted ears in bilateral profound deaf adults.
AB - Patients with hearing loss who underwent cochlear implantation can present
symptomatic or asymptomatic vestibular damages earlier or later after the
surgery. The vestibular permanent lesions could be acute, produced by surgical
trauma or could be progressive due to local morphological changes made by the
presence of the portelectrode in the inner ear (fibrosis related, ossification,
basilar membrane distortion, endolymphatic hydrops). Besides histopathological
findings in inner ear of cochlear implanted patients, the vestibular permanent
damages could be found by assessment of clinical vestibular status. This study
reports the sensorial vestibular functional findings for adults in cochlear
implanted ears related to the electrode insertion type (cochleostomy or round
window approach) and comparing to non-implanted deaf ears. A total of 20 adult
patients with 32 cochlear implanted ears (12 patients with binaural cochlear
implant and eight with monoaural) were selected for postoperatory vestibular
examination by cervical and ocular vestibular myogenic potentials and vestibular
caloric tests. The same tests were made for a control group of 22 non-implanted
deaf ears. Functional testing results were reported related to the electrode
insertion approach. For the cochleostomy group, we found different deficits: in
40% for saccular function, 44% for utricular function, and 12% horizontal canal
dysfunction. In round window group, the deficit was present in 14.29% for
saccular function, 28.57% for utricular function, and 28.58% for horizontal
canal. In 46.88% of implanted ears, the vestibular function was completely
preserved on all tested sensors. In conclusion, the vestibular functional status
after inner ear surgery presents sensorial damages in 53.12% ears compare with
the vestibular dysfunction existing in 50% of deaf non-operated ears. Round
window insertion allows for better conservation of the vestibular function.
PMID- 29940618
TI - The management of the oropharyngeal anterior wall cancer.
AB - INTRODUCTION: Anterior wall of the oropharynx or the base of the tongue is the
site of different types of cancers, most of them usually diagnosed in advanced
stages. The most common histological type of cancer diagnosed in these patients
is squamous cell carcinoma (SCC). The treatment methods are multiple, but the
optimal therapeutic option with best results on outcome and on the patients'
quality life has not been established. The objectives of our study were to
evaluate the tongue base SCCs treated by transhyoid approach and the oncological
outcomes of the surgery combined with radiotherapy. PATIENTS, MATERIALS AND
METHODS: The retrospective study was performed over a period of 10 years (2001
2010) on 37 previously untreated patients. All the tumors were biopsied and after
histopathological (HP) diagnosis, the tumors were excised. All the specimens were
fixed in 4% (v/v) buffered formalin and sent for the HP evaluation. RESULTS: In
the study were included only the patient diagnosed on biopsy with different types
of SCC. The mean age was 61 years old, most of the patients (94.59%) being males.
We performed a tongue base transhyoid tumor resection in 23 (62.17%) cases
followed by epiglottectomy in five (13.51%) cases or horizontal supraglottic
laryngectomy in nine (24.32%) cases, respectively. Bilateral neck dissections and
postoperative radiotherapy were performed in all cases. The postoperative and
post-therapeutic evolution was favorable at three years (81.1%) and five years
(75.67%). There were no signs of local or regional recurrences. The tumor
specific three-year and five-year survival rates were: pT2 100%, pT3 87.5%, pT4a
71.42% and 57.14%, and pT4b 50% and 25%, respectively. The stage specific three
year and five-year survival rates were: stage II 100%, stage III 85.71%, stage
IVA 83.33% and 79.16%, and stage IVB 50% and 25%, respectively. CONCLUSIONS: The
prognosis for the SCC of the tongue base is poor. Cancer resection by transhyoid
approach is a feasible procedure, which permits a good tumor control with limited
postoperative morbidity, with an important benefit on the life quality of the
patients.
PMID- 29940619
TI - Mutational status of KRAS and MMR genes in a series of colorectal carcinoma
cases.
AB - BACKGROUND: The KRAS gene mutation is the most common somatic change in
colorectal carcinoma (CRC) and is predictive of resistance to anti-epidermal
growth factor receptor (EGFR) therapy in the metastatic forms. Microsatellite
instability (MSI), a mismatch repair (MMR) system defect, accounts for 15-20% of
all CRCs, more frequent in early stages. CRCs with MSI present better prognosis,
a distinct histopathological aspect and a different response to chemotherapy.
Patients with both KRAS wild type and MSI have a reduced risk of dissemination
and recurrence. MATERIALS AND METHODS: Our study included formalin-fixed paraffin
embedded tissue samples from 40 patients with metastatic CRCs, aged between 40
and 71 years old, gender (males/females) ratio 2.33:1. The MMR proteins were
analyzed using an indirect bistadial immunohistochemical (IHC) technique with
monoclonal antibodies. KRAS mutations were detected by polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Of the 40
tumors analyzed, 40% presented KRAS mutations located in codon 12 or codon 13.
IHC expression of MMR proteins revealed a microsatellite stable status in 35
cases, including 15 cases with mutated KRAS. MSI status was identified in five
cases (four with KRAS wild type). All MSI tumors had a poorer histological
differentiation and four cases revealed a mucinous phenotype. Eighty percent of
the patients with MSI status were older women. CONCLUSIONS: Our study
demonstrates a 20% frequency of mutated KRAS in MSI CRCs, the incidence of KRAS
mutations being inversely correlated with MSI status in these tumors. MMR protein
deficient CRCs tend to occur in older females, have a poorer differentiation and
are frequently associated with KRAS wild type.
PMID- 29940620
TI - The immunoexpression of p53 and Snail in endometrioid endometrial carcinomas.
AB - Endometrial cancer is one of the most common tumors in women worldwide. P53 has a
well-known function as tumor suppressor, but it can also regulate the tissues
metabolism, differentiation and development. Snail is a zinc-finger transcription
factor, involved in the cell differentiation and survival. We analyzed the
immunoexpression of p53 and Snail in 55 cases of endometrioid endometrial
carcinoma (EEC), in relation with the histopathological prognosis parameters and
tumoral compartments, respectively intratumoral and advancing edge areas. For
both markers, we found a statistically significant association with histological
grade, in relation with tumoral compartments. P53 and Snail can be used in
developing EEC targeted treatment.
PMID- 29940621
TI - Highlighting the R1 and R2 VEGF receptors in placentas resulting from normal
development pregnancies and from pregnancies complicated by preeclampsia.
AB - Preeclampsia (PE), a pathological entity characterized by hypertension and
pregnancy-related proteinuria, is a medical condition of incompletely known
etiopathogenesis. Placental defects and placental angiogenesis may be a cause of
this condition. The main factor that controls angiogenesis in the early stages of
placental development is vascular endothelial growth factor A (VEGF-A) and its
two receptors, namely VEGFR-1 and VEGFR-2. This study analyzed the
immunohistochemical (IHC) expression of the two VEGF receptors, R1 and R2, in
pregnancies complicated by PE compared to pregnancies with a normal evolution.
The pregnancies included into the study for the harvesting of placental tissue to
be microscopically analyzed were divided into two groups: the group of
physiological pregnancies (22 pregnancies) and the group of pregnancies
complicated by preeclampsia (13 pregnancies). For the microscopic analysis, we
used the Hematoxylin-Eosin (HE), Masson's trichrome and IHC stainings. The
microscopic aspects of HE and Masson's trichrome stainings most commonly found in
normal development pregnancies underlie the normal process of placental
senescence. In the case of pregnancies complicated by PE, the microscopic
analysis of the placentas revealed fibrinoid necrosis of the vascular wall, lipid
loaded endothelial cells, diffuse trophoblastic hypertrophy, microinfarctions,
calcification areas, fibrin deposits, vascular-syncytial membrane surface
reduction, basement membrane thickening. According to the established marker
intensity score, the VEGFR-1 and VEGFR-2 receptors were more pronounced in the
placentas resulting from pregnancies complicated by preeclampsia. The present
study brings arguments that support the major regulatory role of VEGF-A and of
the two receptors in the normal or pathological angiogenesis in the placenta, and
implicitly in the pathogenesis of preeclampsia. Further studies are needed for a
more comprehensive analysis of the stages in which these factors cause alteration
of the placental angiogenesis and vasculogenesis processes, so that they can
intervene effectively in the treatment or prevention of this disease.
PMID- 29940622
TI - Morphological features of tongue squamous cell carcinoma diagnosed in Dolj County
population between 2012-2014.
AB - Tongue squamous carcinoma can be found in many forms, having a lot of risk
factors, and whose morphological characteristics can be used as a prognostic. The
purpose of this study was to histologically characterize a number of 54 patients
diagnosed between 2012-2014, with tongue squamous carcinoma. Surgical resection
specimens of tongue tumors were processed by paraffin inclusion technique. The
diagnose samples were reevaluated according to the World Health Organization
(WHO) criteria for head and neck tumors diagnosis, by screening the Hematoxylin
Eosin staining sections. The most common histopathological variety of tongue
carcinoma observed in our cases was the non-keratinized form, the basaloid and
sarcomatoid types of carcinoma being ranked on the last places. The study
outlined the prevalence of non-keratinized forms of tongue squamous carcinoma and
all types of tumoral invasion patterns have been observed in different
percentages.
PMID- 29940623
TI - Adnexal masses in pregnancy: perinatal impact.
AB - The incidence of adnexal masses in pregnancy has increased significantly over the
last decades and this is mostly because of the widespread use of ultrasound for
pregnancy surveillance. Although a clear majority of adnexal masses found in the
first trimester are functional cysts, which have a small diameter and disappear
spontaneously, those that do persist into the second and third trimester require
ultrasound surveillance for proper management. The presence of a large adnexal
mass in the third trimester of pregnancy represents solid grounds for delivery
via Caesarean section (C-section) both because of the risk of dystocia and the
advantage of one-step approach of cystectomy/oophorectomy at the time of C
section. This is a retrospective study of all the third trimester pregnancy
related adnexal masses that delivered in our Hospital in the last 10 years via C
section where cystectomy was also performed. Our aim was to look at the
histological type of ovarian mass and to compare our results to those previously
published by other authors. We also wanted to see whether the clinical suspicion
based on prenatal ultrasound aspect, where this was available, was similar to the
postnatal histology report. Secondary outcomes were gestational age at delivery,
fetal weight and Apgar score. We found that dermoid cysts are the most common
type of adnexal mass with an incidence of 46%, followed by mucous cysts 27%,
serous cysts 18% and endometrioses 9%, which is consistent with the data
published by other authors in larger series. In terms of prenatal clinical
diagnosis, detailed ultrasound assessment of the ovarian mass was available only
in less than half of these cases, but in these, the clinical suspicion was
confirmed by histology report. In our series, we had no case that required
premature delivery because of adnexal mass-related complications and fetal
outcome was very good with normal birth weight and high Apgar score. Although
this is a small series of cases, it confirms the incidence previously published
of the different histological types of ovarian tumors. It also shows that fetal
outcomes are very rarely affected by the presence of ovarian masses and premature
iatrogenic delivery for maternal well-being is the only note wordy one of them.
PMID- 29940624
TI - Vertebral body clinico-morphological features following percutaneous
vertebroplasty versus the conservatory approach.
AB - Most percutaneous vertebroplasty procedures are being performed in order to
relieve pain in patients with severe osteoporosis and associated stable fractures
of one or more vertebral bodies. In addition, vertebroplasty is also recommended
for patients suffering from post-traumatic symptoms associated with vertebral
fractures, patients with large angiomas positioned inside the vertebral body,
with an increased risk for collapse fracture and also patients presenting with
pain associated with vertebral body metastatic disease. On another aspect, it is
possible that in isolated cases, an orthopedic surgeon confronted with a vertebra
plana presentation will recommend bone cement injection into the vertebral bodies
adjacent to the fractured one, in order to have a better and more robust
substrate for placement of screws or other fixation devices. The aim of our study
is to compare results attained by the Department of Interventional Radiology, in
performing this procedure, with results attained by following the classical
orthopedic treatment procedure, involving non-operative treatment, using
medication and bracing varying from simple extension orthoses in order to limit
spinal flexion, light bracing for contiguous fractures, presenting either
angulation or compression, and for severe cases standard thoracolumbosacral
orthoses (TLSOs).
PMID- 29940625
TI - Modern molecular study of weight gain related to antidepressant treatment:
clinical implications of the pharmacogenetic testing.
AB - Antidepressant medication influences cellular lipogenesis, being associated with
metabolic side effects including weight gain. Due to the increasing use of
antidepressants in children and adolescents, their metabolic and endocrine
adverse effects are of particular concern, especially within this pediatric
population that appears to be at greater risk. Genetic factors with a possible
influence on antidepressant's adverse effects include CYP [cytochrome P450
(CYP450)] polymorphisms. We target to evaluate the efficacy of the
pharmacogenetic testing, when prescribing antidepressants, in correlation with
the occurrence of adverse events and weight gain. Our research was performed
between the years 2010 and 2016, in the University Clinic of Child and Adolescent
Psychiatry, Timisoara, Romania. We recruited 80 patients, children and
adolescents with depressive disorders. Our study sample was divided in two
groups: G1 - 40 patients took treatment after pharmacogenetic testing, and G2 -
40 patients without pharmacogenetic testing before the treatment election. Our
results show statistically significant differences concerning the weight gain for
groups G1 (with pharmacogenetic testing) and G2 (without pharmacogenetic
testing). The CYP genotype and the pharmacogenetic testing, for choosing the
personalized antidepressant therapy in children and adolescents with depressive
disorders, proved to be good predictors for the response to antidepressants and
the side effects registered, especially for weight gain. The significant
correlations between the CYP polymorphisms for group G2 (without pharmacogenetic
testing) and the weight gain/body mass index (BMI) increase, as major side
effects induced by antidepressants, proved the fact that the pharmacogenetic
screening is needed in the future clinical practice, allowing for individualized,
tailored treatment, especially for at-risk pediatric categories.
PMID- 29940626
TI - Morphological and ultrasound findings in the placenta of diabetic pregnancy.
AB - The purpose of this study is to analyze the morphological, histological,
immunohistochemical and ultrasound findings in the placenta of maternal type 1
and gestational diabetes, to compare the pathological changes of the placental
structure in the two types of metabolic disruptions, but also to establish
correlations with the expression of these findings, influenced by different
associated conditions. This multicenter study includes 53 pregnancies, of which
37 with pregestational and 16 with gestational diabetes. All cases undergone
specific obstetric ultrasound assessment and detailed placental scan. There were
assessed 49 singleton and four twin pregnancies, all of which having live births
as fetal outcome. Maternal preexisting hypertension, preeclampsia and obesity
were the main associated conditions. Placental ultrasound scan revealed increased
placental thickness even from the second trimester, with significant increases in
the first half, and placentomegaly at the end of the third trimester. Macroscopic
analysis of the placentas and umbilical cords has shown that the placentas of
women with diabetes are heavier, and abnormal cord insertion has been also found.
Gross analysis of maternal and fetal surfaces of the placentas revealed certain
changes in both metabolic conditions. We observed 14 types of placental
pathological findings in pregestational and 11 in gestational diabetes. In
diabetic placenta, it is not appropriate to discuss about specific changes, but
rather about a pathological diabetic pattern, influenced by associated
conditions. Preconceptional and first trimester glycemic control is the key
element, and euglycemia throughout pregnancy is a purpose whose accomplishment
depends the maternal-fetal outcome.
PMID- 29940627
TI - Placental abruption: etiopathogenic aspects, diagnostic and therapeutic
implications.
AB - The severe form of retroplacental hematoma is a serious accident in the second
stage of pregnancy and at birth with frightening for the mother and fetus that
often lead to death. The pathological mechanism presumes conditions for a
"special ground" capital for the "efficiency" of the acute intradecidual vascular
accident with the rupture of the uterus-placental arterioles. The complete
clinical picture of this severe form of retroplacental hematoma - the placental
abruption, observed and mentioned by the classics (vascular drama of Couvelaire)
consists of five syndromes, 18 signs and symptoms, four paradoxes, phenomena not
fully met in the other forms of retroplacental hematoma (minor and intermediate).
The rate of incidence of retroplacental hematoma is in between 0.13-1.38% and
depends on the environment, on the socio-economic and medical conditions, on the
"obstetric education" and associated pathology. Our study aims at re-evaluating
the clinico-paraclinical phenomenon imposed by the dramatism of the phenomenon of
in utero placental apoplexy, the impact on neonatal mortality and on the
functional prognosis from the point of view of surgical climax.
PMID- 29940628
TI - The urologist and child hydronephrosis caused by ureteral anomalies.
AB - Congenital hydronephrosis caused by ureteral anomalies, like ureteral duplicity,
megaureter, ureteral ectopy and ureterocele, must be differentiated from
ureteropelvic junction obstruction (UJO) hydronephrosis and from the
hydronephrosis caused by vesicoureteral reflux. These represent a differentiated
branch of congenital abnormalities in children even if not so common, but this
fact should not be disconsidered. Over a five years period, from 111 operated
children in our Clinic, we performed 13 interventions for congenital
hydronephrosis, 11 (84.61%) being caused by ureteral abnormalities. Here, there
were described particular cases, with diagnosis steps and treatment decisions.
Ureteral ectopy can be manifested by loss of urine drops in cases where ureteral
holes are located in the vagina, septum or urethra, inferior to the sphincter
mechanism. Incontinence in boys never occurs because the ectopic ureter never
opens under the sphincter mechanism. If the ureter opens in the genital tract,
patients may clinically present with the epididymitis symptom. From autopsy
statistics in the US, the incidence of ureteral duplex is estimated to be less
than 1%. When the duplex is associated with urinary infection, the incidence of
ureteral duplex increases up to 8%.
PMID- 29940629
TI - Fluorescence influence on screening decisions for oral malignant lesions.
AB - OBJECTIVES: The aim of the present study was to assess the capability of the low
cost VELscope device to visualize the tissue auto-fluorescence of potentially
malignant oral lesions and to establish the diagnostic accuracy, sensitivity, and
specificity of this method when validating the retrieved data through the gold
standard, i.e., histological examination. PATIENTS, MATERIALS AND METHODS:
Eighteen patients were evaluated by conventional oral examination (COE) followed
by direct visual fluorescence evaluation (DVFE) using VELscope. Areas clinically
suspicious detected by COE or with positive DVFE (visual fluorescence loss) were
further investigated using surgical biopsy. RESULTS: Eight positive biopsies for
malignant lesions were detected by COE and DVFE. Only one positive biopsy for a
premalignant lesion was not in accordance with COE and DVFE. One lesion
identified on the VELscope and COE as a non-malignant lesion was confirmed by the
biopsy. Therefore, the VELscope system had a sensitivity of 94.44% and a
specificity of 100% in discriminating in situ normal mucosa from carcinoma or
from invasive carcinoma, compared with histology. The predictive positive value
was 100% and the negative predictive value was 50%, with a 95% confidence
interval (CI). CONCLUSIONS: DVFE allows for a simple and cost-effective margin
determination, in order to perform the detection and screening of oral
precancerous and early cancerous disorders. It was found that the VELscope system
could not fully replace the histopathology procedure. Nonetheless, the study
demonstrated its usefulness for clinical examination, monitoring oral lesions,
and guiding the biopsy. Therefore, this method may add sensitivity to the oral
tissue examination and be an effective adjunct for high-risk patients.
PMID- 29940630
TI - Morpho-histological assessment of the periodontal support structures under the
action of excessive occlusal forces and under the influence of nicotine.
AB - : Smoking and occlusal trauma are two factors that can interfere with bone
homeostasis. The aim of this study was to evaluate the histocellular changes
occurring in the periodontal ligament and alveolar bone during the action of
excessive occlusal forces, and to assess the influence of nicotine on the
alveolar bone loss in teeth subjected to occlusal trauma. MATERIALS AND METHODS:
Fifty-six Wistar rats were randomized into seven groups (n=8). Animals were
exposed to nicotine and occlusal trauma for 7, 14 and 30 days. Three groups were
exposed to occlusal trauma alone, another three groups were exposed to occlusal
trauma and nicotine, and one group was not exposed to any treatment. RESULTS:
Periodontal lesions induced in the first stage (7-14 days) manifested by a
moderate increase of the periodontal space, a multiplication, thickening and
elongation of periodontal fibers, as well as their condensation in the middle
area of the periradicular space. Regarding bone changes induced by occlusal
trauma, groups 5 and 7 (occlusal trauma and nicotine administration) had higher
bone losses compared to groups 1, 2, 3, 4 and 6. This study demonstrated that
nicotine significantly affected the alveolar bone. CONCLUSIONS: The induced
occlusal trauma caused obvious tissue damage. At the same time, it was found that
nicotine enhanced alveolar bone resorption, increased tooth mobility and induced
an exacerbation of inflammatory processes.
PMID- 29940631
TI - Morphofunctional changes in distribution of pressure center in multiple
sclerosis.
AB - INTRODUCTION: Gait evaluation and assessment of motor performance are of utmost
importance in the clinical management of multiple sclerosis (MS). A new approach
to the analysis of static and dynamic balance of MS patients is the use of
complex biomechanical analysis that includes an analysis of the distribution of
the center of pressure (DCP) and loading, measured by using the pressure and
force platforms. PATIENTS AND METHODS: The study was conducted on a total of 18
patients with MS, with the mean age of 41.2 years old, divided into two groups,
according to the presence of clinically detectable gait disturbances. The
biomechanical analysis that included the assessment of the loading and DPC was
performed using the platform of force distribution. DPC represented the center of
all the forces applied and its value could appreciate the mediolateral stability,
hence the pronation or, respectively, the supination. Group 1, consisting of 12
patients with MS with clinically detectable gait disorders, including six men and
six women, and group 2, of six MS patients without clinically detectable gait
disorders, including two men and four women. RESULTS: For group 1, the center of
pressure had a left-right asymmetric distribution, and also an anterior-posterior
one. There was a predominant distribution at the medial heel, at metatarsals 1-3
and at the hallux. For group 2, the analysis of the plantograms recorded in our
study indicated a tendency of the distribution of the pressure center in the
metatarsals 2, 3 and less in the heel. CONCLUSIONS: The analysis of the loading
and distribution of the pressure center was important not only to appreciate the
static equilibrium disorders but also to appreciate how these disorders affected
the gait initiation, since the patients suffered from anterior-posterior and
mediolateral disorders, which produced spatial and temporal distortion preventing
gait initiation. In the study of pressure and force, we noticed a predominant
distribution on the lateral region of the heel, explained by an attempt of the
body to compensate the disorders of balance and orientation of the reaction force
of the ground to normalize the gait.
PMID- 29940632
TI - Expression and significance of Ki-67 in lung cancer.
AB - Ki-67 parameter is a proliferation marker in malignant tumors. The increased
proliferation activity and the decreased prognosis in lung cancer determined us
to investigate different parameters connected to the tumor's aggression, such as
cellularity, Ki-67 positivity rate, and proliferating cell nuclear antigen
(PCNA). We evaluated the proliferative activity in 62 primary lung tumors by
determining the cell's percentage of Ki-67 and immunoreactive PCNA (using MIB-1
and PCNA monoclonal antibodies), classifying Ki-67 and PCNA immunoreactivity into
three score groups. The results obtained emphasized a linkage between Ki-67 score
with the histological tumor subtype, tumor cellularity and degree of
differentiation and with other proliferation immunohistochemistry (IHC) markers,
such as p53 cellular tumor antigen. The tumor's cellularity, the Ki-67 positivity
rate and PCNA, together with the clinical stage and the histological
differentiation bring extra pieces of useful information in order to anticipate
the evolution and the prognosis of lung cancer.
PMID- 29940633
TI - Morphological assessment of the mandibular canal trajectory in edentate subjects.
AB - BACKGROUND: The mandibular canal and its content represent the vital structure,
which can complicate dentoalveolar surgical procedures in the posterior region of
the mandible. The purpose of the present study was to determine the path the
mandibular canal takes in relation to the horizontal and the vertical anatomical
reference planes in edentate subjects, in order to minimize the risk of affecting
its neurovascular content during various oral surgery procedures. MATERIALS AND
METHODS: Morphometric evaluations were performed on 12 dried fully edentulous
human mandibles and on cone-beam computed tomography (CBCT) cross-sectional
images of the mandible, from 20 patients with either partial or complete
edentulism. Both methods were utilized, in three target areas (corresponding to
the second premolar, to the first molar and to the second molar regions), in
order to measure the distance between the mandibular canal and the following
reference points: (i) the lateral (buccal) surface of the mandible (MC-BS
distance); (ii) the medial (lingual) surface of the mandible (MC-LS distance);
(iii) the alveolar surface of the mandible (MC-AS distance). The results were
statistically processed in Stata MP/13 software package using analysis of
variance (ANOVA) test. RESULTS: The mandibular canal crossed the trabecular bone
from the posterior towards the anterior, and from the lingual towards the buccal,
reaching the premolar region, distal to the mental foramen, where it was located
in the centre of the trabecular bone, main topographic pattern encountered in 27
(84.37%) of the cases. In five (15.63%) of the cases, in the premolar region, the
mandibular canal was located near the buccal cortical plate. The mandibular canal
descended from the second molar region towards the premolar region, main
topographic pattern found in 28 (87.5%) of the cases. In four (12.5%) cases, the
mandibular canal had a descending trajectory in the molar regions and it took a
slightly ascending course in the premolar region. CONCLUSIONS: According to the
results, the second molar region represents the highest risk area in the
accidental injury to the content of the mandibular canal, during various oral
surgery procedures.
PMID- 29940634
TI - The ultrastructural features of the premalignant oral lesions.
AB - Premalignant oral lesions are among the most important risk factors for the
development of oral squamocellular carcinoma. Recent population studies indicate
a significant rise in the prevalence of leukoplakia,
erythroplakia/erythroleukoplakia, actinic cheilitis, submucous fibrosis and
erosive lichen planus. Since standard histopathological examination has numerous
limitations regarding the accurate appreciation of potential malignant
transformation, the present study aims to aid these evaluations using the
transmission electron microscopy (TEM) technique, which emphasizes
ultrastructural changes pertaining to this pathology. Oral mucosa fragments
collected from 43 patients that were clinically and histopathologically diagnosed
with leukoplakia, erosive actinic cheilitis and erosive lichen planus have been
processed through the classic technique for the examination using TEM and were
examined using a Philips CM100 transmission electron microscope. The electron
microscopy study has confirmed the histopathological diagnosis of the tissue
samples examined using photonic microscopy and has furthermore revealed a series
of ultrastructural details that on the one hand indicate the tendency for
malignant transformation, and on the other reveal characteristic features of
tumor development. All the details furnished by TEM complete the overall picture
of morphological changes, specific to these lesions, indicating the importance of
using these techniques in establishing both a correct diagnosis and prognosis.
PMID- 29940635
TI - Effects of moderate exercise and a multiple vitamin and mineral complex on the
arterial wall.
AB - BACKGROUND: Aerobic exercise has favorable effects on vascular structure and
function. Its beneficial role may be due to a decrease in oxidative stress. The
association of vitamin and mineral supplements to exercise determined
contradictory effects on arterial wall and oxidative stress parameters. The aim
of this experimental study was to evaluate the effect of moderate aerobic
exercise, alone or in association with a vitamin and mineral complex, on aortic
wall morphology and oxidant/antioxidant balance. MATERIALS AND METHODS: Four
groups, each of 10 Wistar rats, were included in the study, as follows: (I)
sedentary controls, (II) group subjected to physical exercise, (III) group
subjected to physical exercise and nutritional supplement, and (IV) sedentary
nutritional supplemented group. Aortic wall histological examinations and serum
and aortic wall oxidative stress measurements were performed in each group.
RESULTS: Moderate aerobic exercise induces vascular smooth muscle cell
hypertrophy and transformation in a secretory phenotype. There was a trend for
increase in malondialdehyde (MDA) and decrease in thiol (SH) groups in aortic
tissue homogenates, together with reduction in serum MDA values and increase in
SH groups, after exercise. A reduction in aortic wall lipid peroxidation was
found in supplemented trained animals compared to sedentary group, while no
influence on aortic structure was noted. CONCLUSIONS: Moderate aerobic exercise
induces adaptive modifications in the arterial wall and a favorable effect on
systemic oxidative response. The association of vitamin and mineral supplement
did not influence significantly arterial morphology, while its effects on aortic
oxidative stress suggest an increase in local antioxidant defense.
PMID- 29940636
TI - Factors influencing the pathological quality of the surgical specimen in rectal
cancer - a retrospective single-centre study.
AB - AIM: The pathologist's role in the multidisciplinary treatment of rectal cancer
is to evaluate and stage the tumor according to the latest standards, as well as
indicate the quality of the surgical act. This study aims to evaluate
circumferential and distal resection margins as well as quality of mesorectal
resection and correlate them with different clinical, pathological and
therapeutic factors. PATIENTS, MATERIALS AND METHODS: Four hundred ninety-eight
patients treated radically for mid and low rectal cancer within one Clinic of
Oncological Surgery in Iasi, Romania, were included in this study. RESULTS: The
distal resection margin showed significant correlations with the type of surgical
intervention, chemotherapy in the neoadjuvant treatment plan and pathological
node staging. The circumferential resection margin depended mostly on
pathological node staging and the length of the interval between neoadjuvant
treatment and surgery. Finally, the aspect of the mesorectum varied according to
neoadjuvant treatment and the type of surgical intervention performed.
CONCLUSIONS: The study reached its aim in providing important data for the
expected outcome of the specimen after curative treatment for rectal cancer.
PMID- 29940637
TI - Scanning electron microscopy evaluation of the root canal morphology after Er:YAG
laser irradiation.
AB - The current limits of the endodontic disinfection strategies are not only a
result of bacterial biofilm growth mode inside the root canals, they are equally
due to the anatomical complexity of the root canal system, of its structure, of
the dentin composition and of the factors associated with chemical disinfectants.
One of the major problems is the fact that a great part of the endodontic anatomy
remains uninstrumented after conventional treatment and even the accessible parts
of the root canals are covered in smear layer, which results as a by-product of
the instrumentation and acts as a barrier for irrigants, medication and even
influencing the quality of the endodontic filling. Therefore, strategies in
advanced disinfection in endodontics are developed and tested in order to meet
these challenges. The present study aims to assess the possibility of improving
the debridement of the root canals by using erbium-doped yttrium-aluminum-garnet
(Er:YAG) laser radiation. We used extracted teeth, which were subjected to the
conventional treatment protocol and then divided into three study groups: the
negative control group and two other groups, which were exposed to laser
radiation using two energy levels. Scanning electron microscopy (SEM) revealed
the efficiency of the laser aided treatment versus the conventional methods of
cleaning and disinfection of root canals.
PMID- 29940638
TI - Femtosecond-LASIK outcomes using the VisuMax(r)-MEL(r) 80 platform for mixed
astigmatism refractive surgery.
AB - AIM: To evaluate the predictability, efficacy and safety of Femtosecond-laser
assisted in situ keratomileusis (LASIK) procedure for mixed astigmatism.
PATIENTS, MATERIALS AND METHODS: We prospectively evaluated for 12 months 74 eyes
(52 patients) with mixed astigmatism that underwent Femtosecond-LASIK treatment.
The preoperative mean refractive sphere value was +1.879+/-1.313 diopters (D) and
the mean refractive cylinder value was -4.169+/-1.091 D. The anterior corneal
flap was cut using the VisuMax(r) femtosecond laser and then the stromal ablation
was done using the MEL(r) 80 excimer laser. RESULTS: Mean age was 30.22+/-6.421
years with 61.53% female patients. Postoperative spherical equivalent at 12
months was within +/-0.5D of emmetropia in 75.8% of eyes and within +/-1D in
97.3% of eyes. Postoperative uncorrected distance visual acuity was equivalent to
or better than the preoperative corrected distance visual acuity in 91.9% of
eyes. Compared to the preoperative corrected distance visual acuity (CDVA), 8.1%
of eyes gained one line, 2.7% gained two lines and 2.7% gained three lines of
visual acuity. CONCLUSIONS: Femtosecond-LASIK using the VisuMax(r)-MEL(r) 80
platform appears to have safe, effective and predictable results in mixed
astigmatic eyes. The results are impressive for high refractive error treatment
and for improvement of both uncorrected and corrected distance visual acuity.
PMID- 29940640
TI - An unusual digital neural loop in a cadaver with bilateral high branching median
nerves - case report.
AB - Digital neural loops are present in the palms of most individuals. They can arise
within the common palmar digital nerves (CPDNs) or proper palmar digital nerves
(PPDNs). Typically, common palmar digital arteries (CPDAs) pass through digital
neural loops, however there are reports of loops forming around the superficial
palmar arch or proper palmar digital arteries (PPDAs). We describe an unusual
digital neural loop that involved both a CPDN and a PPDN. To our knowledge, this
is the first documented case of a digital neural loop of this type and therefore
anatomists and surgeons may benefit from an awareness of its existence. A
modification to a current classification system for digital neural loops is
presented to include this novel loop. Interestingly, the cadaver documented in
this report featured a high division of the median nerve in each forearm. On both
sides, the ulnar component of the bifid median nerve followed an intramuscular
course in which it pierced the flexor digitorum superficialis and then continued
into the palm as the 3rd CPDN. A brief review of the literature is provided for
both digital neural loops and the high division of the median nerve variant.
Documented muscle associations noteworthy to the bifid median nerve are
discussed. Developmental connections, if any, that exist between the unique
digital neural loop and the high division of the median nerve are not speculated
upon.
PMID- 29940639
TI - Surgical reconstruction of post-tumoral facial defects.
AB - PURPOSE: The face is an unfortunate location for any type of tumor - malignant or
not - with significant esthetic and functional outcomes. To reconstruct a facial
defect may seem simple, but can be rather complicated. The aim of this study is
to analyze and discuss our results in order to conclude with specific surgical
strategies correlated with the morphopathological results. The most important
objective for us is to offer the highest level of expertise to our patients and
to prove that the symbiosis between the surgical treatment and the work of the
Department of Morphopathology is essential in order to maximize the quality of
medical care provided for our patients. PATIENTS, MATERIALS AND METHODS: A
retrospective study was conducted on 116 patients diagnosed with facial malignant
tumors, 70 of which were confirmed as basal cell carcinomas (BCCs), 35 confirmed
as squamous cell carcinomas (SCCs) and 11 malignant melanomas (MMs). Most BCC
cases (57) showed ulceration, with a long clinical evolution (more than 10 years)
in 48 cases. Only in 12 SCC cases, patients showed inflammation and ulceration,
with a shorter evolution period (2-5 years). For complete microscopic diagnosis,
immunohistochemical (IHC) examination was necessary in 46 cases. The BCC
"deceiving" clinical behavior and the generally aggressive character of the MM
were found in our patients as well. RESULTS: The most frequent sites were the
orbital region (27 cases) and the nasolabial sulcus (26 cases). In order to
reconstruct the postexcisional defects, we had to perform local flaps in 62 cases
(14 frontal flaps for orbital defects, 32 glabellar flaps for medial epicanthus,
lower lid and nasal region, 15 nasolabial flaps for lower lid or nasal alae and
one "Z"-plasty for the submental region). Oncological follow-up was performed in
all patients and in 15 cases re-excision was necessary (11 BCCs, two SCCs and two
MMs). Cervical lymph node metastasis occurred in six cases (three BCCs, one SCC
and two MMs). CONCLUSIONS: The cooperation between surgeons and pathologists
allowed for good outcomes and the pathology examination can guide the surgical
approach towards better results both functionally and esthetically.
PMID- 29940641
TI - An extremely rare case of distal common bile duct adenocarcinoma in a 65-year-old
male patient.
AB - Cholangiocarcinoma is an extremely rare and highly aggressive primary malignancy
of the biliary tract. The current report illustrates a rare case of distal common
bile duct adenocarcinoma encountered in a 65-year-old male patient who was
thoroughly investigated after presenting with a two weeks history of pain in the
right hypochondrium, jaundice and unintentional weight loss (6 kg in two weeks).
The medical team opted for a pancreaticoduodenectomy (Whipple procedure) managing
to obtain negative resection margins of the tumor with a favorable immediate
postoperative evolution. However, the surgical team was forced to reintervene
twice due to complications caused mainly by the patient's disregard.
PMID- 29940642
TI - Cutaneous microcystic/reticular schwannoma: case report and literature review of
an exceedingly rare entity with an unusual presentation.
AB - Conventional schwannoma represents a benign peripheral nerve sheath tumor derived
from Schwann cells, which usually arises in the fourth or fifth decade of life,
in the subcutaneous tissue of the distal extremities, or in the head and neck
region of adult patients, with no gender predilection. In addition to the classic
type, at least 11 different histopathological subtypes have been described and
unawareness of these uncommon histopathological entities may lead to diagnostic
pitfalls and risk of mistreatment. Recently described in the scientific
literature, microcystic/reticular schwannoma is still relatively unknown to both
surgeons and pathologists. The purpose of this paper is to highlight its
existence by describing an additional case that occurred in the retroauricular
area, and to further characterize its clinical, histopathological and
immunohistochemical features. We reviewed the literature and compared the current
case with others that have been documented thus far, discussing all possible
differential diagnoses.
PMID- 29940643
TI - A rare case of signet-ring cell carcinoma associated with poorly differentiated
adenocarcinoma of the non-ampullary duodenum.
AB - Primary duodenal cancer is a rare entity accounting for only 0.3% of all
gastrointestinal cancers. Histopathologically, most duodenal cancers are mucin
producing adenocarcinomas, 34% being poorly differentiated. Signet-ring cell
(SRC) carcinoma is extremely uncommon in the duodenum. Herein, we report a rare
case of SRC carcinoma associated with poorly differentiated adenocarcinoma of the
non-ampullary duodenum in a 74-year-old woman. The patient was admitted to the
hospital for persistent epigastric pain, significant weight loss and hypochromic
microcytic anemia. Esophago-gastro-duodenoscopy revealed a protruded lesion, with
ulceration in the second portion of the duodenum, above the papilla. The patient
was referred to surgery and pancreatico-duodenectomy with lymph node dissection
was performed. The tumor consisted predominately of SRCs, Periodic Acid Schiff
(PAS)-Alcian blue positive. The tumor cells were CDX2, cytokeratin (CK) 7 and CK
18/8 positive, which suggested a primary upper gastrointestinal tract site of
origin. Immunostaining for mucin (MUC) 2 and MUC5AC was also positive
demonstrating the duodenal goblet cells differentiation with a mixed gastric
foveolar and intestinal phenotype. Based on the morphological features and the
immunohistochemical profile, a diagnosis of SRC carcinoma associated with poorly
differentiated adenocarcinoma of the non-ampullary duodenum was set.
PMID- 29940644
TI - Conjunctival melanocytic tumors in children - a challenge in diagnosis and
treatment.
AB - Conjunctival melanocytic lesions are very diverse pigmented tumors that include
benign, premalignant and malignant tumors. The aim of this article is to
highlight the clinical and histopathological aspects of conjunctival melanocytic
tumors at children. This study is a retrospective case series study of three
patients selected from fifteen cases with melanocytic conjunctival tumors who
were operated in the Department of Ophthalmology, "St. Spiridon" Emergency
Hospital, Iasi, Romania. A systematic review of the literature was undertaken,
using an electronic search of PubMed/MEDLINE, Google Scholar and ISI Web of
Knowledge, to identify original English or French articles and reviews on this
subject. Patients were diagnosed by the same doctor between 2004 and 2016, in
ambulatory of Department of Ophthalmology of the same Hospital. The age of
patients was between 7 and 17 years old. Three cases (boys) were treated by
surgery - one patient with conjunctival malignant melanoma (histologically
confirmed) derived from a pre-existing benign conjunctival nevus (diagnosed 1.5
years before), a patient was operated for aesthetic reasons (with histological
diagnosis of compound conjunctival melanocytic nevus) and one boy was diagnosed
of melanocytic conjunctival nevus. All cases operated had normal visual acuity
and fundoscopy. There was no regional lymph node present in any case studied. The
traditional method for clinical diagnosis of suspected pigmented conjunctival
lesions was to remove these lesions surgically and to examine architectural and
cytological features with light microscopy. We recommend an immunohistochemical
staining for the detection of specific cellular antigens in conjunctival
melanocytic tumors in children. The diagnosis, treatment and the follow-up of the
patient were challenges for the ophthalmologist.
PMID- 29940645
TI - Morphological and functional renovascular changes as cause of resistant arterial
hypertension - case report and literature review.
AB - Resistant hypertension is defined by the inability to maintain within normal
limits the blood pressure values of an individual, while he is under treatment
with maximal tolerated doses of three antihypertensive agents. One of the most
common types of resistant hypertension is renovascular hypertension (RVH), which
is caused by the narrowing of the renal arteries, in the context of existing
atherosclerotic plaques at that level. We are presenting the case of a
hypertensive 56-year-old man admitted in the Clinic of Cardiology for a sudden
rise of his blood pressure values, despite undergoing the scheduled treatment.
The abdominal bruit discovered at the clinical examination and the hypokalemia,
together with the mild impairment of the renal function raised the suspicion of
an existing stenosis of the main renal blood vessels. Simple grey scale kidney
ultrasound, Doppler ultrasound of the renal arteries, abdominal computed
tomography and magnetic resonance angiography of the renal arteries, along with
invasive renal angiography demonstrated a smaller right kidney, adrenal
incidentalomas, reduced vascular diameter of renal arteries due to atheromatous
lesions, thrombosis of the infrarenal segment of the abdominal aorta, and reduced
vascular hemodynamics in the same territories. After the renal arteries
revascularization and with minimal antihypertensive treatment, the patient had a
favorable outcome, with normalization of blood pressure and renal function.
Atherosclerotic disease causing renal artery stenosis is essential to be taken
into consideration in the etiopathogenesis of resistant hypertension especially
because RVH is a potentially curable disease.
PMID- 29940646
TI - The cardiac tumors - some exceptional heart conditions.
AB - Cardiac tumors are exceptional cardiac conditions, since they have a minimal
occurrence, according to statistics. The cardiac myxoma cases are the most
dominant for the representative examples for these clinical situations. Those
tumors being benign, the patients enjoy a reasonable life expectancy provided
they receive an early diagnosis. In the absence of potential complications, the
symptoms can vary very much and they may often be non-specific, a fact which
makes it more difficult to establish a proper diagnosis and to quickly tailor the
optimal therapeutic solutions. Surgery is, in the most cases, a comfortable
solution, allowing the cases to be permanently healed. Nowadays, cardiac surgery
provides all the needed facilities to diagnose cases at an early stage, when
diagnosis is quick and accurate. This paper illustrates, by the means of two
suggestive cases, how difficult it is to establish a quick positive diagnosis,
which is vital for healing this condition with an evolutionary risk frequently
worsen by major complications.
PMID- 29940647
TI - Immunohistochemical mismatch in a case of rhabdomyoblastic metastatic melanoma.
AB - Melanomas can exhibit a wide range of unusual morphologies due to the neural
crest origin of melanocytes. Several authors have documented variations in size
and shape of cells, cytoplasmic features and inclusions, nuclear features and
cell architecture. Metastatic melanoma with rhabdomyoblastic differentiation is
an extremely rare condition with poor prognosis. Few studies concerning rhabdoid
or rhabdomyoblastic differentiation in melanoma are currently available and the
current report highlights some of the most important immunohistochemical features
of this rare entity. We report on a case of a rhabdomyoblastic metastatic
melanoma showing intense positivity for both melanocytic and rhabdoid markers in
two cell populations dissociated within the tumor with multiple mismatches in
immunomarker expression. Improved recognition of this rare morphological pattern
may provide the means for developing new techniques to identify novel therapeutic
targets, which would improve the prognostic outlook for these patients.
PMID- 29940648
TI - The curious case of a forehead metatypical basal cell carcinoma.
AB - The risk of developing basal cell carcinoma (BCC) during lifetime varies between
29-55%, while for squamous cell carcinoma (SCC) varies between 7-11%. Between
them, considered to be a BCC, there is a particular histological type, named
metatypical basal cell carcinoma (MTC) or basosquamous cell carcinoma (BSCC). In
this paper, we presented a rare case of metatypical carcinoma of the forehead
with an interesting history of unexpected recurrences, underlining the clinical,
therapeutic and histological essential aspects that may come in use to other
clinicians in managing this type of cancer. In this case, the last recurrent
tumor invaded the external layer of the frontal bone and needed a temporo
parietal flap to cover the large defect, which was previously covered in 2014
using skin grafts. Using Hematoxylin-Eosin (HE) staining, the histological
assessment revealed a basosquamous carcinoma (IDO-O 8094/3, according to World
Health Organization). In addition to the histological aspects revealed using HE
staining, in this case, diffused tumor cells were p63 nuclear positive, which
according to Bircan et al. (2006), it is strongly and diffuse reactive in 82.1%
differentiated, in 77.8% of superficial and in 72.3% of solid undifferentiated
BCCs. The aggressive behavior was revealed by tumor's dimension, local invasion
of the frontal bone with high mitotic rate as seen in the van Gieson and HE
staining, also by the number of recurrences. The prognosis of this case is
reserved due to the number of recurrent tumors, immunohistochemistry anomalies,
involvement of the external layer of the frontal bone, tumor site, gender, poor
remaining reconstructive procedures in case of a relapse, thus, close follow-up
is to be recommended for a period of minimum five years. Recurrent tumors raise
treatment difficulties regarding the reconstruction procedure of the defect after
wide surgical excision. Therefore, the aggressive behavior of the MTC should be
taken into consideration in clinical practice.
PMID- 29940650
TI - A rare case diagnosed as dentin dysplasia type II.
AB - According to their phenotypic features, the hereditary dentin defects in humans
are categorized in two major classes: dentinogenesis imperfecta and dentin
dysplasia. At its turn, the dentin dysplasia is subdivided in dentin dysplasia
type I and dentin dysplasia type II, a milder clinical manifestation of the
condition. Here we report the clinical and radiographic findings of dentin
dysplasia type II in two members of a family, a young adult female and her
mother. Except a mild shade change of the incisal margins in upper central
incisors and left upper canine of the daughter no abnormal occlusal wear or crown
shape change of the teeth were disclosed in both patients. However, confluent
large pulp stones in the thistle-tube shaped pulp chambers and pulpal
obliteration were a common finding. The condition was diagnosed as dentin
dysplasia type II.
PMID- 29940649
TI - An anomalous origin of the gastrosplenic trunk and common hepatic artery arising
independently from the abdominal aorta: a case report using MDCT angiography.
AB - The authors describe a case of a 61-year-old female patient, which presented on
multidetector computed tomographic (MDCT) angiography a gastrosplenic trunk (GST)
and common hepatic artery (CHA) arose independently from abdominal aorta (AA).
The GST arose from the anterior wall of the AA, at the level of upper edge of the
L1 vertebral body. The left gastric artery (LGA) arose from the superior wall of
the GST. The splenic artery (SA) continuous the path of GST. The CHA arose from
the anterior wall of the AA, at the level of upper one third of the L1 vertebral
body, at 15.3 mm above the origin of superior mesenteric artery (SMA). The
incidence and developmental and clinical significance of this vascular variation
is discussed with a detailed review of the literature.
PMID- 29940651
TI - Neurosurgical rare disease: solitary plasmacytoma of the skull - case report and
literature review.
AB - Solitary extranevraxial plasmacytoma (SEP), as a clinical entity without signs of
systemic myelomatosis, is extremely rare; it is difficult to find literature on
the issue of patient management and proper course of action in the presence of
associated pathology. The authors present a rare case of plasmacytoma of the
skull vault associated with severe cardiac pathology, which made surgery
extremely difficult and possible only through temporization of the interventions,
as presented. We discuss our findings and opportunities for treatment in this
case, which seemed unapproachable at presentation, in connection with the
associated cardiac pathology. The case was followed-up for eight years with no
recurrences.
PMID- 29940652
TI - Conjunctival invasive poorly differentiated squamous cell carcinoma in a 91-year
old female patient.
AB - The invasive conjunctival squamous cell carcinoma (SCC) of the eyeball is a
malignant tumor that invades only the conjunctiva and rarely the eyeball and the
tissue of the orbit. We presented the clinical case of a 91-year-old patient,
hospitalized at the 2nd Ophthalmology Clinic of the "Prof. Dr. Nicolae Oblu"
Emergency Clinical Hospital of Iasi, Romania, due to a solid tumor mass of
approximately 1*2 cm, which was noticed under the bulbar conjunctiva of the right
eye in the nasal sector. The magnetic resonance imaging (MRI) examination showed
an adherent tumor of the right eye sclera, presenting invasion into the tissue of
the orbit. The right eyeball was enucleated en bloc with the adherent tumor and
the partial exenteration of the nearby orbital tissue was carried out as well.
The pathological examination revealed that the immunohistochemical (IHC)
reactions turned positive for the anti-cytokeratin AE1/AE3 antibody and showed a
relatively high Ki67 labeling index, but it did not show immunoreactivity for
human melanoma black-45 (HMB-45) marker and S100 protein. The histopathological
(HP) diagnosis was poorly differentiated SCC of the right ocular conjunctiva with
infiltration of cornea, sclera and orbital connective and adipose tissues
(pT4N0M0). The invasive conjunctival SCC requires an early diagnosis for elderly
patients in order to prevent the ocular and orbital invasion and the appearance
of metastases. This tumor rarely occurs during the ninth life decade, the
literature reporting only three cases. HP examination of the lesion is the gold
standard for diagnosis, especially when IHC stainings are added.
PMID- 29940653
TI - Empty sella associated with growth hormone deficiency and polydactyly.
AB - Empty sella means the absence of the pituitary gland on cranial computed
tomography or magnetic resonance imaging. Empty sella syndrome is the
pathological variant of the imaging-described empty sella. We present the case of
a male Caucasian child, aged four years and two months, for short stature and
diagnosed by imaging procedures as empty sella. The cause of short stature was
isolated growth hormone (GH) deficiency. Associated he presented left hand
postaxial polydactyly. In connection with this particular case, we propose a
review of current knowledge in empty sella syndrome. The particularity of
reported case consists of association empty sella with GH deficiency and
polydactyly. The association of empty sella with polydactyly is not reported yet
in the medical literature and is probably coincidental.
PMID- 29940654
TI - Low-fat, plexiform spindle cell lipoma of the lip expressing S100 protein: a
neural tumor simulator.
AB - The plexiform variant of spindle cell lipoma is very uncommon. In fact, as far as
we are aware only seven cases have been previously reported. We describe herein
the case of a 49-year-old man with a smooth nodule of the mucosa of the lower lip
that was gradually increasing. Surgical excision of the lesion was done and the
study revealed the histological and immunohistochemical features of a plexiform
spindle cell lipoma (PSCL). Peculiar to this case was the location in the lip,
the presence of abundant S100-positive dendritic cells, and scarce mature
lipogenic cells. S100 protein reactivity has rarely been observed in classical
and plexiform spindle cell lipoma. To our knowledge, no case of PSCL displaying
abundant S100-positive dendritic cells has been described. This feature may lead
to a diagnostic pitfall. The main differential diagnosis includes the neuroma
group, plexiform intraneural neurofibroma (PIN), plexiform schwannoma and
plexiform hybrid tumor of perineurioma and cellular neurothekeoma. It is
imperative correctly diagnose and differentiate PSCL from neural tumors because
they may show syndromic associations, have different prognosis, including
malignant transformation in PIN, and the management of all these lesions differs.
PMID- 29940655
TI - Letter to the Editor: Desquamative interstitial pneumonia revisited half a
century later.
PMID- 29940656
TI - Letter to the Editor: Corrigendum to the paper "Precursor and interstitial Cajal
cells in the human embryo liver".
PMID- 29940657
TI - Genetic Risk Factors and Inhibitor Development in Hemophilia: What Is Known and
Searching for the Unknown.
AB - Over the past few decades, important knowledge on why inhibitors develop and
better information about significant risk factors have become available. A series
of both genetic and nongenetic factors are recognized and clinical score systems
were proposed to quantify the risk for each patient. In addition, modulation of
the immunological response was acknowledged to play a pivotal role in the
occurrence of inhibitors. However, with the exception of mutation testing in
severe hemophilia B patients, no single risk factor or clinical score is
currently utilized in clinical practice. "Omics" technologies are large-scale
hypothesis-generating approaches, which provide the tools to study issues
contributing to a complex and multifactorial phenomenon, such as inhibitor
development. Newer cutting edge technologies may enable a more accurate
estimation of the personal risk profile and provide a reliable tool to accurately
measure the risk periodically, thereby enabling strategies to foresee and prevent
inhibitor formation.
PMID- 29940658
TI - [Factors Affecting Long-Term Cosmetic Results after Minimally Invasive Video
Assisted Thyroidectomy and Conventional Thyroid Surgery].
AB - INTRODUCTION: Approximately 90,000 thyroid operations are performed in Germany
each year. Minimally invasive video-assisted thyroidectomy (MIVAT) accounts for 5
- 10% of these operations. There are few data that compare long-term cosmetic
results after MIVAT to those after conventional surgery. Current systematic
reviews show no advantage for MIVAT. The goal of this study was to analyse the
long-term postoperative results in both procedures and the evaluation of relevant
factors. PATIENTS AND METHODS: The analysis of the long-term results is based on
follow-up examinations using a validated method for scar appraisal (POSAS).
Cohort analysis was performed on MIVAT operations in our hospital between 2004
and 2011 and conventional thyroid operations in 2011. RESULTS: Follow-up
examination data were analysed from 117 patients from the MIVAT group and 102
patients from the conventional group. The follow-up examination was performed
with a mean of 23.1 vs. 23.6 months postoperatively (MIVAT vs. conventional). The
Friedman Test showed that scar pigmentation (mean rank 4.79) and scar surface
structure (mean rank 3.62) were the deciding factors influencing the long-term
cosmetic results. CONCLUSION: Both MIVAT and conventional surgery gave very good
long-term cosmetic results. From the patient's perspective, there is no
significant advantage with conventional surgery. The evaluation of the long-term
results largely depends on factors such as scar pigmentation and surface
structure that can only be influenced to a limited extent by the surgical
procedure.
PMID- 29940659
TI - [Maternal Deaths Worldwide Falling - But Commonly Preventable].
AB - According to data from the WHO, maternal mortality ratio has dropped worldwide by
44% between 1990 and 2015, yet more than 300,000 mothers still die annually,
about 99% of them in the developing countries. In some developed countries the
incidence of maternal deaths has even increased during the past 2 decades. The
leading causes of direct maternal deaths are haemorrhage (nearly 3-quarters from
postpartum haemorrhage), pulmonary embolism including amniotic fluid embolism,
and hypertensive disorders of pregnancy; the leading cause of indirect maternal
deaths is cardiac disease of the mother. The most important step to prevent
maternal deaths is the accurate evaluation of each death by a multidisciplinary
committee of independent experts, followed by consensus-based agreement on the
underlying cause of death, the quality of care, and whether or not the death was
preventable. The UK Confidential Enquiries into Maternal Deaths and Morbidity are
internationally recognized as the 'gold standard' in maternal mortality
surveillance. Considering the 11 studies from different developed countries,
nearly 50% of direct maternal deaths (range: 26-75%) are potentially preventable,
most often those due to postpartum haemorrhage and hypertensive disorders of
pregnancy, and the fewest of all due to amniotic fluid embolisms. The crucial
point is to learn from failures leading to maternal deaths: each obstetric unit
should scrutinise if and where the need for improvement exists to prevent severe
maternal morbidity and mortality.
PMID- 29940660
TI - Single-Lab Validation for Determination of Kavalactones and Flavokavains in Piper
methysticum (Kava).
AB - Piper methysticum (Kava) is a plant whose roots are used in the preparation of
traditional beverages with spiritual, medicinal, and social importance for the
Pacific Islanders. Kava is also sold as a herbal supplement or recreational
beverage consumed for its mild inebriating effect in Europe and North America.
With an ongoing interest in the safety and quality of kava products, it is
necessary to develop a validated method for determination of kava chemical
composition to ensure confidence in quality assessment. Thus, an high-performance
liquid chromatography with ultraviolet detection (HPLC-UV) method was developed,
optimized, and validated for determining six major kavalactones and three
flavokavains in kava raw materials and finished products based on AOAC single
laboratory validation guidelines. This is the first fully validated analytical
method for measuring kavalactones and flavokavains in a single run. The
separation of the analytes was achieved in 10 min with an Agilent Poroshell C18
column using gradient separation. The sample was extracted with methanol first
and then acetone. The signals were detected at 240 nm and 355 nm. The limit of
quantification was under 1.2 ug/mL (0.3 mg/g) for kavalactones and under 0.35
ug/mL (0.01 mg/g) for flavokavains. The Horwitz ratio values described ranged
from 0.3 to 1.82. The spike recovery experiments showed an accuracy between 92
and 105% for all analytes. The results of the study demonstrate that the method
is fit for the purpose of determining methysticin, dihydromethysticin, kavain,
dihydrokavain, yangonin, desmethoxyyangonin, flavokavain A, flavokavain B, and
flavokavain C in kava raw material and finished products (dry-filled capsule,
liquid phytocaps, and tincture).
PMID- 29940661
TI - Anti-inflammatory Ingenane Diterpenoids from the Roots of Euphorbia kansui.
AB - Bioassay-guided fractionation of the ethanolic extract of the roots of Euphorbia
kansui led to the isolation of two new ingenane diterpenoids, euphorkans A (1: )
and B (2: ), together with 16 known analogues (3: - 18: ). Their structures were
determined by combined spectral and chemical methods. All the isolates were
evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide
production in RAW264.7 macrophage cells. Compounds 1: - 6: and 10: - 13:
exhibited pronounced inhibitory activity with IC50 values in the range of 2.78 -
10.6 uM, and were more potent than the positive control, quercetin (IC50 = 15.8
uM). Compounds 1: and 5: were selected for further assays toward the key
inflammation mediators TNF-alpha and IL-6, and showed a significant inhibition in
a dose-dependent manner. The preliminary mechanistic study revealed that 1: and
5: inhibited NF-kappaB activity, which may exert a role in their anti
inflammatory activity.
PMID- 29940662
TI - Kampo, A Japanese Traditional Medicinal System for Psychiatric Conditions: A
Narrative Review.
AB - INTRODUCTION: Kampo is a Japanese traditional medicinal system and is represented
by unity of mind and body. It is originally based upon Chinese traditional
medicine but has uniquely developed in Japan. METHODS: A narrative review on the
use of Kampo for psychiatric conditions is provided. RESULTS: Kampo formula is a
combination of several crude ingredients; most derive from natural plants and
some from animals and minerals. These Kampo formulae are widely prescribed in
almost all medical disciplines, including psychiatry, in Japan; they have been
used for various psychiatric disorders such as dementia, schizophrenia spectrum
disorders, mood disorders, anxiety disorders, and personality disorders. Kampo is
a versatile traditional medicine with a variety of positive effects on mental
states with relatively benign side effect profiles. Kampo formulae can be
adjunctively combined with or substituted for the Western psychotropic drugs,
which will provide more treatment options to patients with psychiatric
conditions. DISCUSSION: This review summarizes the current knowledge on Kampo for
psychiatric conditions, highlighting a paucity of data and a need for further
good-quality evidence on these medications.
PMID- 29940663
TI - PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum.
AB - BACKGROUND: Primary microcephaly and profound global developmental delay have
been considered the core clinical phenotype in patients with bi-allelic PRUNE1
mutations. METHODS: Linkage analysis and whole-exome sequencing (WES) in a
multiplex family and extraction of further cases from a WES repository containing
571 children with severe developmental disabilities and neurologic symptoms.
RESULTS: We identified bi-allelic PRUNE1 mutations in twelve children from six
unrelated families. All patients who survived beyond the first 6 months of life
had early-onset global developmental delay, bilateral spastic paresis, dysphagia
and difficult-to-treat seizures, while congenital or later-evolving microcephaly
was not a consistent finding. Brain MRI showed variable anomalies with
progressive cerebral and cerebellar atrophies and T2-hyperintense brain stem
lesions. Peripheral neuropathy was documented in five cases. Disease course was
progressive in all patients and eight children died in the first or early second
decade of life. In addition to the previously reported missense mutation
p.(Asp106Asn), we observed a novel homozygous missense variant p.(Leu172Pro) and
a homozygous contiguous gene deletion encompassing most of the PRUNE1 gene and
part of the neighboring BNIPL gene. CONCLUSIONS: PRUNE1 deficiency causes severe
early-onset disease affecting the central and peripheral nervous systems.
Microcephaly is probably not a universal feature.
PMID- 29940664
TI - MicroRNA-204-3p Attenuates High Glucose-Induced MPC5 Podocytes Apoptosis by
Targeting Braykinin B2 Receptor.
AB - BACKGROUND: Previous study has been reported that braykinin B2 receptor (Bdkrb2)
involves in high glucose-induced renal and podocytes injuries. However, there
have been some studies with contradictory results that Bdkrb2 has a protective
effect on hyperglycemia-induced injuries in vivo and in vitro. The purpose of the
present study was carried out to further investigate the post-transcriptional
regulatory mechanism of microRNA (miR) in high glucose-treated podocytes by
targeting Bdkrb2 signaling in vitro. METHODS: The CCK-8 and flow cytometry were
performed to measure the cell viability and apoptosis. Gene and protein
expression were assayed by RT-qPCR and western blotting, respectively. RESULTS:
High glucose treatment decreased cell viability and induced membrane and DNA
damage, as well as apoptosis in podocytes. High glucose treatment also increased
the expression of Bdkrb2, which was blocked by miR-204-3p mimics transfection in
podocytes. Bioinformatics and luciferase reporter activity showed that miR-204-3p
was directly targeted to the 3'-untranslated region (3'-UTR) of Bdkrb2. High
glucose-induced apoptosis and dysfunction in podocytes were reserved by miR-204
3p mimics transfection, while the effects of miR-204-3p mimics in high glucose
treated podocytes were neutralized by overexpressed Bdkrb2. CONCLUSIONS: These
findings suggested that miR-204-3p may play a protective role in high glucose
induced apoptosis and dysfunction in podocytes through down-regulation of Bdkrb2.
PMID- 29940665
TI - Giant Prolactinomas: Outcomes of Multimodal Treatments for 42 Cases with Long
Term Follow-Up.
AB - Giant prolactinomas represent a rare entity of pituitary tumors so that the
management of these patients is still a prevalent challenge at present. Paying
special attention to the treatment strategy and outcomes, we presented a large
series of 42 cases looking forward to share our understanding and experience in
management of these patients. Male patients accounted for 71.4% of this series
and were relatively younger (35.70+/-2.42 vs. 52.00+/-3.55 years, p=0.0011) and
harbored bigger tumors (14.57 vs. 7.74 cm3, p=0.0179) compared to females. Almost
all of these tumors showed suprasellar extension (97.6%) and cavernous sinus
invasion (92.9%). Dopamine agonist represented an efficient method to control PRL
concentrations (98.8%) and reduce tumor burdens (81.2 %). PRL normalization was
detected in 13 out of the 27 patients initially treated with bromocriptine (BRC)
whereas none of the 14 patients with first-line operation gained a normalization
of PRL concentration after surgery. Although there was no reliable predictor of
tumor response, First PRL reduction was a predictive criterion for the nadir PRL
level during the long-time period of follow-up for first-line bromocriptine
treatment. In conclusion, patients with giant prolactinomas did not gain more
benefits from initial surgery. Dopamine agonist (BRC) should be first-line
treatment for giant prolactinomas whereas operation merely served as a remedy for
acute compression symptoms and dopamine agonist resistance. Consecutive
monitoring of serum PRL levels in the early stage of initial BRC treatment is
useful for evaluation of therapeutic effect and further therapeutic decision.
PMID- 29940666
TI - Immune and Inflammatory Response in Atopic Elite Endurance Athletes.
AB - The present study aimed to compare the immune and inflammatory responses between
atopic (n=20) and non-atopic (n=39) elite endurance athletes. Fifty-nine elite
runners and triathletes were assessed for the following measurements: Th1, Th2
and lymphocyte phenotyping and plasma levels of cortisol, chemokines,
inflammatory cytokines and specific immunoglobulin E (IgE). Levels of salivary
IgA, allergic symptoms and training data were also evaluated. No difference was
observed in baseline lymphocyte levels. However, the Th1 lymphocytes of atopic
athletes presented a lower response after activation. In contrast to this result,
levels of salivary IgA and CXCL9 chemokine were higher in the atopic athletes. It
was observed that the volume of training per week was linearly associated with
Th1 levels, allergic symptoms and IgE levels. In addition, linear multiple
regression analysis demonstrated that the volume of training was the only factor
associated with allergic symptoms in atopic athletes (r=0.53; p=0.04). These
results suggest that compared to non-atopic athletes, atopic athletes present a
reduced Th1 response and higher levels of salivary IgA. Training volume is
associated with the immune response and allergic symptoms, which suggests that
they may play a role in the atopy in elite endurance athletes.
PMID- 29940667
TI - Incidence of Achilles and Patellar Tendinopathy in Adolescent Elite Athletes.
AB - The study investigated the incidence of Achilles and patellar tendinopathy in
adolescent elite athletes and non-athletic controls. Furthermore, predictive and
associated factors for tendinopathy development were analyzed. The prospective
study consisted of two measurement days (M1/M2) with an interval of 3.2+/-0.9
years. 157 athletes (12.1+/-0.7 years) and 25 controls (13.3+/-0.6 years) without
Achilles/patellar tendinopathy were included at M1. Clinical and ultrasound
examinations of both Achilles (AT) and patellar tendons (PT) were performed. Main
outcome measures were incidence tendinopathy and structural intratendinous
alterations (hypo-/hyperechogenicity, vascularization) at M2 [%]. Incidence of
Achilles tendinopathy was 1% in athletes and 0% in controls. Patellar
tendinopathy was more frequent in athletes (13%) than in controls (4%). Incidence
of intratendinous alterations in ATs was 1-2% in athletes and 0% in controls,
whereas in PTs it was 4-6% in both groups (p>0.05). Intratendinous alterations at
M2 were associated with patellar tendinopathy in athletes (p<=0.01).
Intratendinous alterations at M1, anthropometric data, training amount, sports or
sex did not predict tendinopathy development (p>0.05). Incidence of tendinopathy
and intratendinous alterations in adolescent athletes is low in ATs and more
common in PTs. Development of intratendinous alterations in PT is associated with
tendinopathy. However, predictive factors could not be identified.
PMID- 29940668
TI - Eccentric Overload Muscle Damage is Attenuated By a Novel Angiotensin- (1-7)
Treatment.
AB - The development of new strategies to attenuate exercise-induced muscle damage may
be helpful for training regimens. The aim of this study was to determine whether
a oral formulation of angiotensin Ang-(1-7)[HPbetaCD/Ang-(1-7)] is effective to
reduce pain, and muscle damage markers after eccentric-overload exercise.
HPbetaCD (Placebo) and HPbetaCD/Ang-(1-7) (Ang-(1-7) group were treated for 7
days (one capsule/day). The pain was measured by visual analogue scale, maximal
strength (MS) using force platform. Blood samples were collected for cytokines
and creatine kinase (CK) analysis. The Ang-(1-7)-treated group reported less pain
immediately (3.46+/-0.64 vs. placebo 3.80+/-0.77 cm) and 24 h after exercise
(3.07+/-0.71 vs. 3.73+/-0.58 cm placebo) and higher MS at 24 h (24+/-12 N) and 48
h (30+/-15 N) vs. placebo (-8+/-9 N and -10+/-9 N). The CK for Ang-(1-7) (0.5+/
0.1 and 0.9+/-0.2 U/L) were lower at 48 and 72 h vs. placebo (fold changes of
1.7+/-0.5 and 1.5+/-0.3 U/L). The TNF-alpha level was lower in the treated group
post-exercise (38+/-2.5 pg/ml) vs. placebo (45+/-2.9 pg/ml) but no significant
changes were observed for IL-6 and IL-10. Our data indicate that treatment with
Ang-(1-7) may attenuate pain, some of the muscle damage markers and improves
performance following eccentric exercise.
PMID- 29940669
TI - Short-term Dehydroepiandrosterone Intake and Supramaximal Exercise in Young
Recreationally-trained Women.
AB - WADA has banned dehydroepiandrosterone (DHEA) but its ergogenic effect in female
athletes has never been investigated. The aim of this study was to determine
whether short-term DHEA intake would improve performance during a supramaximal
field exercise in healthy young recreationally trained women. Its impact on body
composition, metabolic responses was also measured. Eleven young female
volunteers completed four running-based anaerobic sprint tests: just before and
after treatment with either oral placebo or DHEA (100 mg/day/28days), following a
double-blind and randomized protocol. Bioelectrical impedance assessed body
composition. At rest and after passive recovery, blood samples were collected for
lactate measurement and saliva samples for DHEA, testosterone and cortisol
analysis. There was no significant difference in body composition or performance
parameters after DHEA administration, despite a tendency toward increased peak
power and decreased fat mass. However, DHEA treatment induced a very marked
increase in saliva DHEA and testosterone concentrations (p<0.001), with no change
in cortisol or lactate levels. In conclusion, short-term DHEA administration did
not improve performance or have an anabolic effect in young female recreationally
trained athletes, despite the increase in androgenic hormones. Further studies
are needed to determine whether a higher daily dose would generate an ergogenic
effect during anaerobic exercise.
PMID- 29940670
TI - Exercise Training Plus Sildenafil Treatment: Role on Autonomic and Inflammatory
Markers.
AB - The current study aimed to determine the effects of sildenafil-associated aerobic
exercise training (ET) on the physical performance, hemodynamic, autonomic and
inflammatory parameters of rats. Male Wistar rats were randomly assigned to:
sedentary rats placebo-treated (SP); sedentary rats sildenafil-treated (SS);
trained rats placebo-treated (TP); and trained rats sildenafil-treated (TS).
Sildenafil treatment consisted of 8 weeks of daily oral gavage (1.5 mg/kg), one
hour before the session of ET (60-75% of maximal running speed, 5 days/week, for
8 weeks). After ET period, physical capacity, hemodynamic, autonomic and skeletal
muscle inflammatory profile were assessed. Chronic sildenafil treatment causes an
additional increase of physical capacity in aerobically trained rats. However,
these beneficial effects were accompanied by unwanted alterations, as increased
of arterial pressure and peripheral sympathetic modulation, as well as
exacerbated inflammatory status on skeletal muscle of rats. Taken together, these
data suggest the positive and negative effects of sildenafil chronic
administration, associated to aerobic ET, at doses used in clinical practice.
This report stresses the importance of paying greater attention to the
indiscriminate use of this substance in high-performance sports.
PMID- 29940671
TI - Influence of the Lower Body on Seated Arm Cranking Performance.
AB - During upper-body tasks, use of the lower body is important for minimizing
physiological strain and maximizing performance. The lower body has an integral
role during standing upper-body tasks, however, it is less clear if it is also
important during seated upper-body tasks. We determined the extent to which the
lower body influenced seated arm cranking performance. Eleven males performed
incremental (40+20 W.3 min-1) and short-duration maximal effort (5 s, 120 rpm)
arm cranking trials with and without lower-body restriction. The lower body was
restricted by securing the legs to the seat and suspending them off the floor.
Upper-body peak oxygen consumption (VO2peak) and maximal power were determined.
At the end of the incremental protocol, lower-body restriction reduced VO2peak by
14+/-12% (P<0.01) compared to normal arm cranking. At greater submaximal stages
(60-100% isotime) heart rate, ventilation, RER, and arm-specific exertion
increased to a greater extent (all P<0.05) with lower-body restriction. During
short duration maximal arm cranking, lower-body restriction decreased maximal
power by 23+/-9% (P<0.01). Results indicated that lower-body restriction limited
aerobic capacity, increased physiological strain during high-intensity submaximal
exercise, and compromised maximal power generating capacity. These results imply
that use of the lower body is critical when performing seated arm cranking. Our
findings have implications for exercise testing, training and rehabilitation.
PMID- 29940673
TI - Recent Developments in Antiphospholipid Antibodies and the Antiphospholipid
Syndrome.
PMID- 29940674
TI - Rough sailing on a sea of gray [Editorial].
PMID- 29940675
TI - Balloon catheter dilation of a septated frontal sinus.
PMID- 29940676
TI - An undulating vallecular cyst.
PMID- 29940677
TI - Aggressive desmoid fibromatosis of the neck after total thyroidectomy.
PMID- 29940678
TI - A rare cause of dysphagia: Pyriform sinus atypical lipomatous tumor.
PMID- 29940679
TI - Microcomputed tomography of the stapes: Wide-ranging dimensions.
AB - Although human stapes are known to have varied dimensions and the footplate is
considered to be oval (fitting as it does into the oval window), few studies of
high-resolution imaging of these structures have been performed. No study appears
to have addressed the bilateral symmetry of stapes dimensions or to have
determined if an association exists between the size of the stapes and the size
of mastoid pneumatization; a small mastoid pneumatization is an indicator of
childhood otitis media. We obtained 41 ear-normal cadaver crania specimens for
study in our temporal bone laboratory and isolated 10 for further analysis: the 5
with the largest areas of mastoid pneumatization and the 5 with the smallest.
Microcomputed tomography of tissue blocks was performed on the in situ stapes.
Using ImageJ software, we created a three-dimensional model of each stapes. The
mean height of these stapes was 3.43 mm (range: 3.20 to 3.80), the mean length of
the footplates was 2.71 mm (range: 2.52 to 2.97), and the mean width of the
footplates was 1.23 mm (range: 1.12 to 1.46). Qualitatively, the footplate was
shaped like a human footprint in moist sand, as Eysell described in 1870. The
dimensions of the stapes were found to be bilaterally symmetrical in general, but
there was no correlation between these dimensions and the size of mastoid
pneumatization. The distribution of footplate widths may be bimodal, which is
consistent with the observation of Sim et al that men have wider footplates than
do women.
PMID- 29940680
TI - An absence of cilia outer microtubules, an etiology not previously recognized in
bilateral mucocele.
AB - Most paranasal sinus mucoceles are unilateral and affect one or at most two
contiguous sinuses. We describe the case of a 44-year-old woman with bilateral
maxillary sinus mucoceles who presented clinically with left malar pain, right
sided swelling, and proptosis of the right eye. The diagnostic workup included
computed tomography and magnetic resonance imaging. In addition, because of the
atypical bilateral presentation, we analyzed mucosal sinonasal tissue samples by
electron microscopy. Microscopic analysis revealed an absence of one of the
microtubule doublets in three of the outer doublets of the axoneme, thereby
establishing a diagnosis of isolated ciliary dysfunction. To the best of our
knowledge, ciliary dysfunction as a cause of bilateral mucoceles has not been
previously reported in the literature. The patient underwent successful surgery
for removal of the mucoceles, and she exhibited no evidence of recurrence at the
18-month follow-up. When a diagnosis of bilateral mucocele formation is made, we
suggest that ciliary dysfunction be considered in the differential diagnosis and
that electron microscopy of the sinonasal mucosa be performed in the workup.
PMID- 29940681
TI - Computational analysis of swallowing mechanics after surgery for obstructive
sleep apnea.
AB - Multilevel upper airway surgery for obstructive sleep apnea (OSA) has been shown
to cause clinically significant dysphagia in some patients. We describe the cases
of 2 adults with OSA who developed persistent dysphagia after multilevel upper
airway surgery. Patient-specific computational analysis of swallowing mechanics
(CASM) revealed absent pharyngeal shortening and aberrant tongue base retraction
in both patients. These findings are consistent with the OSA surgical goal of
enlarging the hypopharyngeal airway but likely contributed to our patients'
dysphagia. Patient-specific CASM allows for sensitive identification of
swallowing mechanical dysfunction that might otherwise be overlooked, and it may
be utilized in future head and neck surgery patients to analyze swallowing
dysfunction associated with treatment.
PMID- 29940682
TI - Vocal tract symptoms: Severity and frequency in patients on statins.
AB - The objective of the study was to analyze the frequency and severity of vocal
tract symptoms in patients on statins. A total of 73 patients were enrolled in
this study, 44 patients who were taking statins and 29 controls not taking
statins. The severity and frequency of vocal tract discomfort was assessed using
the Vocal Tract Discomfort scale. The most frequent vocal tract symptom in
patients on statins was dryness followed by tightness and lump sensation. The
difference in the mean of the total score and in the mean frequency of any vocal
tract symptom was not significant between patients taking statins and controls.
The most severe (highest mean values) vocal tract symptom in patients taking
statins also was dryness followed by tightness and lump sensation. The difference
in the mean of the total score and in the mean severity of any vocal tract
symptom between patients taking statins and controls was not significant. This
study failed to demonstrate a higher prevalence or severity of vocal tract
symptoms in patients receiving statins. Despite the lack of a significant
difference in the means of vocal tract discomfort symptom frequency and severity,
this study carries clinical significance when considering that a higher
prevalence and severity of vocal tract discomfort symptoms should alert
physicians to the possible development of statin-induced myotoxicity in the
laryngopharyngeal complex.
PMID- 29940683
TI - Undifferentiated sarcoma presenting as a slowly enlarging facial mass.
AB - Head and neck sarcomas are rare and consist of a variety of histologic subtypes.
We present a case of undifferentiated/unclassified sarcoma (UUS) of the maxillary
sinus, a tumor subtype historically known as malignant fibrous histiocytoma (MFH)
or undifferentiated pleomorphic sarcoma (UPS). A 50-year-old female patient
presented with worsening facial pain and dysphagia. Physical examination
demonstrated a large, ulcerated mass protruding from the oral cavity. Computed
tomography demonstrated a large, enhancing mass centered in the right maxillary
sinus with local invasion. The initial biopsy was read as "central giant cell
granuloma." Conservative management yielded no improvement, and the tumor grew
steadily. The patient underwent a total maxillectomy with resection of the
orbital floor and an anterior ethmoidectomy, followed by radiation and
chemotherapy. In addition to treatment of this patient, we discuss a review of
the literature and the clinical presentation, radiologic, and histologic findings
of this disease.
PMID- 29940684
TI - Anxiety, depression, and hopelessness in patients before and after treatment for
peripheral facial paralysis.
AB - We conducted a prospective study to investigate the effectiveness of
pharmacologic treatment on alleviating facial paralysis, as well as the anxiety
and depression that are associated with it. Our study population was made up of
105 patients-59 men and 46 women, aged 18 to 60 years (mean: 38.2)-who had acute
idiopathic peripheral facial paralysis. Before treatment, paralysis was
classified as House-Brackmann grade II or III in 44 patients (41.9%) and grade IV
to VI in the remaining 61 (58.1%). After treatment, 73 patients (69.5%) improved
to grade I, 29 (27.6%) were at grade II or III, and only 3 (2.9%) remained at
grade IV or higher. Mean scores on the Beck anxiety inventory, the Beck
depression inventory, and the Beck hopelessness scale were 20.30, 19.75, and
7.57, respectively, before treatment and 5.72, 5.68, and 2.85 afterward; the
difference in all three measures was statistically significant (p < 0.001). We
found no correlation between the degree of facial paralysis and anxiety levels (r
= 0.094, p = 0.338) or depression levels (r = 0.181, p = 0.064). Clinicians
should consider asking patients with peripheral facial paralysis about their
feelings of anxiety, depression, and hopelessness and refer them for a
psychiatric consultation if necessary.
PMID- 29940685
TI - Early experience in endoscopic transoral resection for parapharyngeal space
tumors.
AB - The purpose of this study was to investigate the feasibility, safety, and
efficacy of the resection of parapharyngeal space (PPS) tumors via an endoscopic
transoral approach. We reviewed 9 patients who were diagnosed with PPS tumors and
who were treated with an endoscopic transoral approach. PPS tumors ranging from
2.5 to 6 cm were removed completely with no complications and excellent recovery
(mean inpatient hospital stay: 6.89 days). Pathology was pleomorphic adenoma (n =
7), schwannoma (n = 1) and malignant pleomorphic adenoma (n = 1). For the
malignant lesion, the patient underwent postoperative radiotherapy (70 Gy). There
was no radiographic evidence of recurrences, with mean follow-up of 11.22 months
(range: 3 to 20). We conclude that resection of PPS tumors via an endoscopic
transoral approach appears to be feasible, safe, and effective. Potential
advantages of this approach include an excellent surgical view, rapid surgical
access, less tissue injury, avoidance of external scar, fewer postoperative
complications, and less morbidity.
PMID- 29940686
TI - Surgical treatment of symptomatic subglottic stenosis during the third trimester
of pregnancy.
AB - Subglottic stenosis is a narrowing of the airway distal to the glottis. Airway
narrowing can be severe and, when coupled with pregnancy, can pose a significant
threat to the mother and fetus. There is sparse literature describing treatment
of these critical patients, posing a challenge for management. We describe our
experience with a 31-year-old woman with idiopathic subglottic stenosis who
became symptomatic during her pregnancy, requiring surgical intervention early in
her third trimester. The following case report describes this patient's
presentation and management, in which an awake dilation technique was used. We
also include a literature review on the management of subglottic stenosis in
pregnancy.
PMID- 29940687
TI - A unique manifestation of Langerhans cell histiocytosis: Diagnostic and
therapeutic considerations of atypical cases.
AB - Langerhans cell histiocytosis (LCH) is regarded as a clonal disease, usually
carrying the activating BRAF mutation V600E. Although LCH theoretically may
affect all types of human tissue and typically appears during childhood, temporal
bone involvement in adult patients is exceedingly rare. We report an atypical
case of a 56-year-old man as one of the oldest patients diagnosed with temporal
bone involvement of a BRAF-negative LCH, which caused painless otorrhea and
hearing loss. Cutaneous manifestation (multifocal multisystem LCH, also known as
Letterer-Siwe disease) was later recognized incidentally. Administration of
ifosfamide plus doxorubicin and mesna with supplementary irradiation resulted in
a temporary remission followed by slow but constant tumor progression, which
after 2.5 years became resistant to treatment with cytarabine and dasatinib.
Attempts at therapy (cladribine) to achieve cure are ongoing.
PMID- 29940688
TI - Esthesioneuroblastoma with widespread distant metastasis: Case report and
literature review.
AB - Esthesioneuroblastoma (ENB) is an uncommon sinonasal tract tumor, and it is even
more uncommon among all neoplasms. Literature regarding the incidence and spread
of the disease is limited. The prognosis of metastatic disease is poor. In this
report, we present a case of recurrent ENB in a young woman involving metastasis
to the neck, lungs, and ovary. Metastasis to the cervical lymph nodes is
relatively common, but metastasis to the lungs is rare. Furthermore, to our
knowledge, no cases of ovarian metastases of ENB have been reported. This case
highlights the potential for widespread metastatic disease, suggesting the need
for more frequent and thorough surveillance of patients diagnosed with
recurrences of this tumor.
PMID- 29940689
TI - Screening and management of postoperative hypoparathyroidism-induced hypocalcemia
in thyroidectomized patients in the endocrine ward compared with the surgical
ward.
AB - Transient hypoparathyroid-associated hypocalcemia is a common side effect after
thyroidectomy. Not only may it be life-threatening, but it also can distinctly
affect length of hospital stay and treatment costs. Screening and treatment
practices are suspected to differ between clinicians in endocrine and surgical
wards. We therefore compared discipline-related differences in screening and
treatment of hypocalcemia as well as the length of hospital stay of patients
after thyroidectomy. Data from 170 patients treated with total thyroidectomy in
the Department of Otolaryngology (n = 29), General Surgery (n = 49) and
Endocrinology (n = 92) were analyzed, and measurements of postoperative calcium
and parathyroid hormone, calcium at time of discharge, percentage of discharge
with a calcium level <1.9 mmol/L (defined as severe hypocalcemia), treatment of
hypocalcemia, and duration of hospitalization were compared between disciplines.
Postoperative calcium levels were measured in 97.8% of patients in endocrine
wards compared with 83.3% in surgical departments (p = 0.001), and discharge with
a calcium level <1.9 mmol/L was statistically more frequent in surgical vs.
endocrine wards. Additional to calcium supplementation, active vitamin D was
administered in 95% of patients treated in endocrine wards vs. 35% in surgical
wards. Length of hospitalization was 8.12 (+/-6.62) days (endocrinology) to 10.55
(+/-9.39) days (surgical wards) (p = 0.05). Monitoring of calcium levels is an
important indicator of the quality of postoperative care after thyroidectomy. To
prevent postoperative hypocalcemia-induced complications and to reduce the length
of hospital stay, an interdisciplinary approach for the management of
hypocalcemia after thyroidectomy might be a promising model for future treatment
concepts.
PMID- 29940690
TI - Powered irrigation with suction evacuation for chronic rhinosinusitis in the
office setting: A pilot study.
AB - Bacterial infections in the form of adherent biofilms are frequently implicated
in the pathogenesis and recalcitrance of chronic rhinosinusitis. The
Hydrodebrider, a disposable powered irrigation and suction device, has been
developed specifically to remove biofilm from the paranasal sinuses. We conducted
a prospective study to evaluate the tolerability and efficacy of the
Hydrodebrider in the office setting with the use of local anesthesia. Of the
original 13 adults we recruited, 10 completed the entire study protocol. All
enrolled patients had previously undergone sinus surgery that involved the
creation of a maxillary antrostomy large enough to allow placement of a
Hydrodebrider device, and the endoscopic findings in all patients were consistent
with chronic sinusitis. The standard visual analog scale for pain (range: 0 to
10) was used to measure tolerability. The 20-Item Sino-Nasal Outcome Test (SNOT
20) for symptoms was completed at baseline and at 1 and 8 weeks after the
procedure. The mean pain score obtained immediately after the procedure was only
2.3, indicating that the procedure was well tolerated. The mean SNOT-20 score
trended toward improvement during the first week, but then returned to near
preprocedure levels at 8 weeks. In conclusion, powered irrigation with suction is
a well-tolerated procedure in the office setting and might be a useful short-term
adjunct in the management of recalcitrant chronic sinusitis.
PMID- 29940691
TI - Horizontal (vs. vertical) closure of the neo-pharynx is associated with superior
postoperative swallowing after total laryngectomy.
AB - We conducted a cross-sectional study to compare the horizontal and vertical
methods used in the surgical closure of the neo-pharynx after total laryngectomy
in terms of their effect on swallowing function, swallowing-related quality of
life (QOL), and overall QOL. We also assessed the potential influence of age
(<=64 vs. >=65 yr) and the type of treatment modality (primary, salvage, or total
laryngectomy with radiotherapy) on outcomes. Our final study population was made
up of 34 patients-31 men and 3 women, aged 49 to 89 years (mean: 66.8)-who had
undergone a total laryngectomy. One year after surgery, all patients were asked
to complete the M.D. Anderson dysphagia inventory (MDADI), which quantifies
swallowing function and swallowing-related QOL, and the University of Washington
quality-of-life questionnaire (UW-QOL), which quantifies overall QOL. Of the 34
patients, 16 had undergone a horizontal surgical closure of their neo-pharynx and
18 a vertical closure. According to the MDADI, patients in the horizontal group
experienced significantly better swallowing function/QOL; the mean composite
MDADI scores were 91.5 in the horizontal group and 68.3 in the vertical group (p
= 0.005). We found no significant difference in terms of overall QOL, as the
respective mean UW-QOL scores were 81.0 and 80.8 (p = 0.93). The population
correlation coefficient was positive in both groups, but more so in the
horizontal group (rhohorizontal = 0.876 and rhovertical = 0.676). Neither age nor
the type of treatment modality employed influenced swallowing function/QOL (page
= 0.10, ptreatment modality = 0.78) or overall QOL (page = 0.08, ptreatment
modality = 0.59). We conclude that horizontal closure of the neo-pharynx is
superior to vertical closure in terms postoperative swallowing function/QOL but
not overall QOL.
PMID- 29940692
TI - Wireless mobile ultrasonography-assisted parotid duct stone removal.
AB - Ultrasonography is highly sensitive for the diagnosis of sialoliths. Recently,
wireless mobile ultrasonography was developed. We describe the case of a 49-year
old man who presented with painful postprandial left cheek swelling. Computed
tomography detected a solitary 5-mm parotid duct stone with infection at the
anterior portion of the left masseter muscle. Transoral stone removal was
planned, although difficulty was expected in view of the surrounding infection.
Surgery was performed under the guidance of mobile ultrasonography, and the stone
was removed safely.
PMID- 29940693
TI - Iatrogenic external auditory canal stenosis induced by silver nitrate.
PMID- 29940694
TI - Testing Reliability of the Computational Age-At-Death Estimation Methods between
Five Observers Using Three-Dimensional Image Data of the Pubic Symphysis.
AB - In an effort to standardize data collection and analysis in age estimation, a
series of computational methods utilizing high-dimensional image data of the age
indicator have recently been proposed as an alternative to subjective visual,
trait-to-phase matching techniques. To systematically quantify the
reproducibility of such methods, we investigate the intrascan variability and
within- and between-observer reliability in initial scan data capturing and
editing using 3D laser scans of the Suchey-Brooks pubic symphysis casts and five
shape-based computational methods. Our results show that (i) five observers with
various training background and experience levels edited the scans consistently
for all three trials and the derived shape measures and age estimates were in
excellent agreement among observers, and (ii) the computational methods are
robust to a measured degree of scan trimming error. This study supports the
application of computational methods to 3D laser scanned images for reliable age
at-death estimation, with reduced subjectivity.
PMID- 29940695
TI - The Current Status of Drug Discovery and Development as Originated in United
States Academia: The Influence of Industrial and Academic Collaboration on Drug
Discovery and Development.
AB - Academic drug discovery is a vital component to current drug discovery and
development environments. In this study, we investigated 798 drug discovery
projects that took place between 1991 and 2015 at 36 academic institutions in the
United States. The observed success rates of academic drug discovery and
development were 75% at phase I, 50% at phase II, 59% at phase III, and 88% at
the new drug application/biologics license application (NDA/BLA) phase. These
results were similar to the corresponding success rates of the pharmaceutical
industry. Collaboration between academic institutions and the pharmaceutical
industry seemed more important at later stages than earlier ones; all projects
that succeeded at phase III or the NDA/BLA stage involved academic-industrial
collaboration. Many academic research projects involved neoplasms and infectious
diseases, and were focused on small molecules and biologics. The success rates
and possible effects of academic-industrial collaboration seemed to vary
depending on disease domains and drug modalities.
PMID- 29940696
TI - Adipocere Formation in Subtropical Climate of Northern India: A Retrospective
Study.
AB - Adipocere formation depends upon multiple environmental factors. In comparison
with temperate countries, it usually develops early in the subtropical climate.
We have studied a retrospective data of 31 cases with adipocere formation at
Department of Forensic Medicine at All India Institute of Medical Sciences, New
Delhi. Most of the cases were recovered during the month of May to October from
closed rooms at home, open grounds, open forest areas, various water sources, and
riverbanks. The time duration of recovery from the time of death was from 12 h to
7 days 12 h. In 10 cases, adipocere formation was seen within 2 days, and in four
male cases among them, the adipocere formed within a day. Most of the bodies
showing adipocere formation within 2 days were recovered from land. These facts
showed that subtropical climate having hot and humid weather promotes early
adipocere formation compared to temperate climate.
PMID- 29940697
TI - Intra- and Inter-Element Variability in Mitochondrial and Nuclear DNA from Fresh
and Environmentally Exposed Skeletal Remains.
AB - Successful identification of skeletonized remains often relies upon DNA analyses,
frequently focusing on the mid-diaphysis of weight-bearing long bones. This study
explored intra-bone DNA variability using bovine and porcine femora, along with
calcanei and tali. DNA from fresh and short-term environmentally exposed bone was
extracted utilizing demineralization and standard lysis buffer protocols, and DNA
quantity and quality were measured. Overall, femoral epiphyses, metaphyses, and
the tarsals had more nuclear and mitochondrial DNA than did the femoral
diaphyses. DNA loss was much more rapid in buried bones than in surface exposed
bones, while DNA quality differed based on environment, but not bone
region/element. The demineralization protocol generated more DNA in some bone
regions, while the standard lysis was more effective in others, and neither
significantly affected DNA quality. Taken together, these findings reinforce the
importance of considering inter- and intra-bone heterogeneity when sampling
skeletal material for forensic DNA-based identifications.
PMID- 29940698
TI - Acetyl Fentanyl: Trends and Concentrations in Metro Detroit.
AB - Acetyl fentanyl (N-[1-phenethylpiperidin-4-yl]-N-phenylacetamide) is a potent
opioid analgesic with no medicinal uses. We report deaths between 2016 and 2017
at the Medical Examiner's Office in Detroit, MI where acetyl fentanyl was found
in the decedent's blood and compare them to previously published deaths between
2015 and 2016. The recent cases (cohort B) had a mean acetyl fentanyl
concentration of 0.9 ng/mL (range: 0.1-5.3 ng/mL) and an associated higher
concentration of fentanyl along with multiple other drugs present. The older
cases (cohort A) had higher concentrations of acetyl fentanyl (mean: 8.9 ng/mL;
range: 0.28-37 ng/mL) with lower, yet still toxic, concentrations of fentanyl. We
conclude that the cause of death in these recent cases was likely multiple drug
toxicity with fentanyl and that the consistently observed lower peripheral blood
concentrations of acetyl fentanyl are most likely an artifact in the manufacture
of the consumed illicit fentanyl.
PMID- 29940700
TI - Previously Unreported Complication of Coronary Artery Bypass Grafting: Suture
Rupture Resulting in Patient's Death.
AB - Traditionally, the manner of death in most hospital autopsy cases is natural, in
which death is due to the natural course of disease or reasonably anticipated
outcomes of medical interventions. Some cases fall into a potential gray zone
between natural and accident, including rare or unanticipated outcomes of medical
interventions. We present a case of a patient postcoronary artery bypass graft.
Autopsy revealed the proximal anastomosis of the aorta-to-first-diagonal-coronary
artery-to-second-obtuse-marginal-artery graft was detached from the aorta. A
broken suture was present at the disconnected anastomosis, with intact knots but
was broken along its length. In-hospital mortality rates of CABG range from 1% to
3%, with several autopsy studies identifying surgical complications as the cause
of death in one-third of perioperative deaths. No publications were found that
described suture rupture as directly relating to the cause of death. This case
report describes a previously unreported complication of coronary artery bypass
grafting.
PMID- 29940699
TI - Gating control and K+ uptake by the KAT1 K+ channel leaveraged through membrane
anchoring of the trafficking protein SYP121.
AB - Vesicle traffic is tightly coordinated with ion transport for plant cell
expansion through physical interactions between subsets of vesicle-trafficking
(so-called SNARE) proteins and plasma membrane Kv channels, including the
archetypal inward-rectifying K+ channel, KAT1 of Arabidopsis. Ion channels open
and close rapidly over milliseconds, whereas vesicle fusion events require many
seconds. Binding has been mapped to conserved motifs of both the Kv channels and
the SNAREs, but knowledge of the temporal kinetics of their interactions,
especially as it might relate to channel gating and its coordination with vesicle
fusion remains unclear. Here, we report that the SNARE SYP121 promotes KAT1
gating through a persistent interaction that alters the stability of the channel,
both in its open and closed states. We show, too, that SYP121 action on the
channel open state requires SNARE anchoring in the plasma membrane. Our findings
indicate that SNARE binding confers a conformational bias that encompasses the
microscopic kinetics of channel gating, with leverage applied through the SNARE
anchor in favour of the open channel.
PMID- 29940701
TI - Pacemaker programmer for reliable differentiation of selective and nonselective
His bundle capture.
PMID- 29940702
TI - Apple bZIP transcription factor MdbZIP44 regulates abscisic acid-promoted
anthocyanin accumulation.
AB - Phytohormone abscisic acid (ABA) induces anthocyanin biosynthesis; however, the
underlying molecular mechanism is less known. In this study, we found that the
apple MYB transcription factor MdMYB1 activated anthocyanin biosynthesis in
response to ABA. Using a yeast screening technique, we isolated MdbZIP44, an ABA
induced bZIP transcription factor in apple, as a co-partner with MdMYB1. MdbZIP44
promoted anthocyanin accumulation in response to ABA by enhancing the binding of
MdMYB1 to the promoters of downstream target genes. Furthermore, we identified
MdBT2, a BTB protein, as an MdbZIP44-interacting protein. A series of molecular,
biochemical, and genetic analysis suggested that MdBT2 degraded MdbZIP44 protein
through the Ubiquitin-26S proteasome system, thus inhibiting MdbZIP44-modulated
anthocyanin biosynthesis. Taken together, we reveal a novel working mechanism of
MdbZIP44-mediated anthocyanin biosynthesis in response to ABA.
PMID- 29940703
TI - Fatalities Due to Failure of Continuous Subcutaneous Insulin Infusion Devices: A
Report of Six Cases.
AB - Diabetes mellitus type 1 and type 2 are diseases characterized by impaired
regulation of blood glucose due to decreased insulin production and insulin
resistance, respectively. Management of diabetes mellitus often requires
injection of exogenous insulin. Continuous subcutaneous insulin infusion (CSII or
insulin pump) is a diabetes treatment modality utilizing a device to aid in
regulation of glycemic control. Malfunctions in device components can have rare
fatal consequences. Described in this report are six fatalities due to one such
malfunction, the failure of plastic cannulas of CSII devices to penetrate the
skin and deliver insulin, resulting in fatal diabetic ketoacidosis (DKA). The
cases derive from four different death investigation systems. For each case,
scene and autopsy findings are presented, as well as selected toxicology and
histology findings. These cases illustrate the importance of careful examination
of CSII devices in death investigations and introduce a discussion on discrepant
manner of death classifications.
PMID- 29940704
TI - Fine structure of spermatophores of some Oribatid mites (Acari, Arachnida).
AB - The ultrastructure of spermatophores was studied in seven species of Oribatei.
Each spermatophore is composed of a head and a stalk which is attached to the
substratum. The spherical head consists of two distinct portions: (1) the sperm
package; and (2) the head matrix. Position and structure of the sperm package are
described in the different species, as well as the various structures in the head
matrix. The sperm package contains sperm embedded in secretory products. The most
characteristic feature of the sperm is an electron-dense chromatin body.
Mitochondria lie adjacent to it or are partly or completely incorporated into the
chromatin body. The cytoplasmic surface of the plasma membrane regularly bears an
electron-dense layer; the plasma membrane is covered by a secretory sheath. The
spermatophores of the Oribatei are structurally complicated and not uniform. The
possible role of the spermatophore's structural elements is discussed and an
attempt is made to evaluate characteristic features taxonomically.
PMID- 29940705
TI - Evolutionary trends in adrenal gland of anurans and urodeles.
AB - Morphological, histological, ultrastructural, and developmental research on the
adrenal gland of several species of anurans and urodeles belonging to different
families is presented. Urodeles show a large variability in adrenal glandular
structure without a clear taxonomic pattern, although increased compactness of
the gland and mingling of steroidogenic and chromaffin cells are found only in
some neourodeles. In anurans the glandular pattern may be divided into two
subtypes: one more medial and diffuse, which is observed in frogs of the more
primitive families; the other more lateral and aggregated, as seen in the more
advanced families. The adrenal gland therefore increases in its compactness and
aggregation of chromaffin and steroidogenic tissues in the transition from
primitive to advanced families, both in urodeles and anurans. Until the end of
metamorphosis, morphogenesis of the gland is similar in all amphibians studied.
This process is extended after metamorphosis in the advanced anurans, in order
that the gland may reach its definitive position.
PMID- 29940706
TI - Histological and cytological structure of the gastrointestinal tract of the
luderick, Girella tricuspidata (pisces, kyphosidae), in relation to diet.
AB - The gastrointestinal tract of Girella tricuspidata, an herbivorous teleost, is
differentiated into esophagus, stomach, pyloric caeca, intestine, and rectum. The
mucosa of the esophagus consists almost entirely of elongated secretory cells,
with an underlying submucosa and prominent circular and longitudinal muscle
layers. The anterior part of the stomach contains a mucous surface epithelium and
a network of tubular glands having only one type of glandular cell, to which
secretion of both pepsinogen and HCl is attributed. The tubular glands are not
present in the pyloric region. The gastric wall contains well developed circular
muscle and submucosal layers. The pyloric caeca contain a mucosa containing two
types of exocrine cells. The nature and function of secretions from these cells
is discussed. The intestinal mucosa is differentiated into an anterior (ca. 30%)
and a posterior section. The enterocytes of the anterior portion show evidence of
lipid absorption, while those of the posterior intestine and rectum show
considerable pinocytotic activity. The pyloric caeca, intestine, and rectum have
a layer of submucosa and a thin layer of circular muscle. The presence of the
prominent circular muscle in both the esophagus and the stomach is postulated to
be advantageous to an herbivorous fish. However, other ultrastructural features
of the gastrointestinal tract of the luderick are similar to those described in
carnivorous fish and appear to show no specialization for herbivory.
PMID- 29940707
TI - Gut-associated lymphoid tissue (GALT) of the goldfish, Carassius auratus.
AB - The head kidney and spleen are major sites of haemopoiesis in fish; a secondary
center is found in loose connective tissue of the intestine. In this study we
determined the nature of gut-associated haemopoietic tissue in the goldfish,
Carassius auratus, using light and electron microscopy. This tissue is a loose
stroma of reticular cells and fibers vascularized by capillaries, venules, and
arterioles. The cellular population includes lymphoblasts, small and medium-sized
lymphocytes, plasmocytes, macrophages, and various granulocytes. The most
abundant granulocyte is the mast cell, whose large granules stain with Alcian
blue and toluidine blue. Heterophils are found in the intestinal connective
tissue as well as two other granulocytes: one with ovoid granules having dense
parallel lamellae and another with granules containing crystalline inclusions.
Immature forms of both granulocytes were also noted. Macrophages containing
phagocytosed debris were often located close to the epithelium; they were
observed forming clusters with lymphocytes. The epithelium contained a number of
migrating leucocytes including lymphocytes and lymphoblasts, macrophages, and
heterophils. Although many granulocytes were found in the connective tissue,
granulopoiesis does not seem to be a major function. Gut-associated haemopoietic
tissue in goldfish resembles diffuse lymphoid tissue and may be involved in
intestinal immune responses.
PMID- 29940708
TI - Mastication in the musk shrew, Suncus murinus (mammalia, Soricidae).
AB - High-speed cinematography shows that Suncus murinus (Crocidurinae) masticates
fast (mean 5.5, 5-10 masticatory cycles per sec). Their grasping behavior is not
stereotyped. The unilateral mandibular movements combine vertical,
anteroposterior, and lateral displacements; and any masticatory sequence may
include crushing, repositioning, shearing, and grinding components. Size and
consistency of food influence the duration of individual chewing cycles. As food
is transferred to the new working side, the chewing direction reverses, either
near maximum closure or near maximum opening. An unfused mandibular symphysis
permits tilting movements of the two halves of the mandible. Food may be squeezed
between the lower incisors. The working side tilts outward during closing; this
may improve shearing or grinding action. The closing phase is posteriorly
directed. Thus, the masticatory movements of these shrews differ from those that
have been described in many other mammals.
PMID- 29940709
TI - Fine structure of the doliolaria larva of the feather star Florometra
serratissima (Echinodermata: Crinoidea), with special emphasis on the nervous
system.
AB - The epidermis of the doliolaria larva of the Florometra serratissima is
differentiated into distinct structures including an apical organ, adhesive pit,
ganglion, ciliary bands, nerve plexus, and vestibular invagination. All these
structures possess unique cell-types, suggesting that they are functionally
specialized in the larva, except the vestibular invagination that becomes the
postmetamorphic stomodeum. The epidermis also contains yellow cells, amoeboid
like cells, and secretory cells. The enteric sac, hydrocoel, axocoel, and
somatocoels have differentiated but are probably not functional in the doliolaria
stage. Mesenchymal cells, around the enteric sac and coeloms, appear to be
actively secreting the endoskeleton and connective tissue fibers. The nervous
system is composed of a nerve plexus, ganglion, and sensory receptor cells in the
apical organ. The apical organ is a larval specialization of the anterior end;
the ganglion is located in the base of the epidermis at the anterior dorsal end
of the larva. The nerve plexus underlies most of the epidermis, although it is
more prominent in the anterior region. Here, processes from sensory receptor
cells of the apical organ, as well as those from nerve cells, contribute to the
plexus. These processes contain one or a combination of organelles including
vesicles, vacuoles, microtubules, and mitochondria. The configuration of
glyoxylic acid-induced fluorescence, revealing catecholamine activity, correlates
to the apical organ, nerve cells, and nerve plexus. Morphological evidence
suggests that the nervous system may function in initiation and control of
settlement, attachment, and metamorphosis. The crinoid larval nervous system is
discussed and compared to that found in other larval echinoderms.
PMID- 29940710
TI - Homology and evolution of the deep dorsal thigh musculature in birds and other
reptilia.
AB - Data from adult birds, crocodilians, Sphenodon, squamates, turtles, and from the
chick embryo are compared to test conflicting hypotheses of homology of the deep
dorsal thigh muscles of birds and other reptiles. This comparison suggests that:
(1) avian Mm. iliofemoralis externus and iliotrochantericus caudalis (herein
renamed "iliofemoralis cranialis") are homologous with M. iliofemoralis of other
reptiles; (2) avian Mm. iliotrochanterici cranialis and medius are homologous
with one of two divisions of M. pubo-ischio-femoralis internus found in other
reptiles (pars dorsalis of Crocodylia); (3) avian M. iliofemoralis internus
(herein renamed "cuppedicus") is homologous with the other division of M. pubo
ischio-femoralis internus (pars medialis of Crocodylia). This hypothesis implies
a minimum of seven transformations in the number of muscles and their positions
of origin and insertion in the evolution of Aves, five of which are recapitulated
during ontogeny of the chick. The traditional recognition of three muscles in the
"iliotrochantericus group" is topographically accurate, but it is a misnomer and
has been a source of misdirection when these muscles are studied in a
phylogenetic context. Variations within Aves in the presence of the
iliotrochantericus muscles (cranialis or medius) and the iliofemoralis muscles
(externus or cranialis) are results of heterochronic perturbations of a conserved
developmental program. Unlike most previous interpretations, this view of
homology suggests that the evolution of avian bipedality was accompanied by few
myological transformations, despite profound modification of the skeleton.
PMID- 29940711
TI - Evolution of the female cuticular organ in the asellota (crustacea, isopoda).
AB - In an effort to understand the variation and probable origin of a female
copulatory organ found in isopods of the asellote superfamily Janiroidea, the
morphology of female reproductive structures among the Asellota was surveyed.
Examples of four asellote superfamilies were studied using whole mount staining
after potassium-hydroxide maceration or clearing with lactic acid. In
contradiction to previous conclusions, the cuticular organ is shown to occur in
the more primitive Asellota, although the position of its opening varies
considerably. In the genera Asellus, and Stenetrium, Munna, and Santia, the
cuticular organ originates adjacent to the oopore, and in the remaining
janiroidean isopods, it is placed dorsally and usually anteriorly. This
information permits a simple hypothesis explaining the origin of the cuticular
organ: it was present in the proximate ancestor of the Asellota and evolved to
the janiroidean condition by anterodorsal migration.
PMID- 29940712
TI - Evidence of a microtrabecular cytoskeletal lattice in glandular cells of
hydrozoan planulae.
AB - Hydrozoan planulae of Pennaria tiarella and Podocoryne carnea were processed for
transmission electron microscopy using diethylene glycol distearate (DGD). The
DGD functions as a removable embedding medium to produce embedment-free sections
of intact planulae. Images of glandular cells obtained using embedment-free
sections were compared with those from conventional Spurr-embedded sections. In
unembedded sections a large number of thin anastomosing fibers were observed
throughout the cytoplasm of the glandular cell. The fibers appeared to coalesce
in certain areas to form thick bundles of fibers that partitioned the glandular
cytoplasm into spherical compartments. The meshwork of fibers is three
dimensional and resembles a microtrabecular lattice. Mitochondria are suspended
within and attached to the network of fibers, thus suggesting a cytoskeletal role
of the fibers. This study documents the presence of a cytoplasmic fiber system
within cells of intact invertebrate larvae.
PMID- 29940713
TI - Fine structure of the hemocytes and nephrocytes of Argas (Persicargas) arboreus
(Ixodoidea: Argasidae).
AB - The fine structure of the hemocytes and nephrocytes in Argas (Persicargas)
arboreus is described and compared with that of similar cells in other tick
species and insects. The hemocytes are of three types: prohemocytes, with a
relatively undifferentiated cytoplasm lacking granular inclusions and probably
serving as progenitors of the other hemolymph cell types; plasmatocytes,
containing abundant mitochondria, cisternae of rough endoplasmic reticulum (RER),
and free ribosomes, as well as some small granular inclusions; granulocytes, the
predominant cell type in the hemolymph, containing numerous granules of variable
electron density and maturity, and pseudopodia-like processes on the cell
surface. Plasmatocytes and granulocytes are phagocytic and possibly also have
other functions in the tick body. Cells with intermediate features appear to be
in a stage of transition from plasmatocyte to granulocyte. Nephrocytes contain
vacuoles enclosing fibrillar material, some electrondense granules, and moderate
amounts of the active organelles-mitochondria, RER, and ribosomes. The nephrocyte
is surrounded by a basal lamina and its plasma membrane infolds to form many deep
invaginations coated by a fine fibrillar material. Openings to these
invaginations are closed by membranous diaphragms. Coated tubular elements
connect the surface invaginations with large coated vesicles, which appear to be
specialized for internalization of proteins from the hemolymph. The dense
granules may represent an advanced stage of condensation of ingested protein and
thus may be lysosomal residual bodies, or they may develop by accumulation of
secretory products.
PMID- 29940714
TI - Taik-Won Kim, the First Korean Clinical Psychiatrist.
PMID- 29940715
TI - Posttraumatic Stress Disorder Symptoms and Posttraumatic Growth Following
Indirect Trauma from the Sewol Ferry Disaster, 2014.
AB - Objective: The definition of psychological trauma, which was traditionally
restricted to immediate and direct experience, is now expanding to include
mediated or vicarious experience. So the present study aims to examine the
relationship between the negative effects and the positive outcomes to a national
disaster by assessing the posttraumatic stress disorder (PTSD) symptoms and
posttraumatic growth of the general public. Methods: A nationwide survey of the
Korean population (n=811) who were exposed to the Sewol ferry disaster through
the media participated in this research, completing a self-report questionnaire
consisting of demographic characteristics, Impact of Event Scale-Revised- Korean,
and Korean-Stress-related Growth Scale-Revised. The participants were divided
into three groups according to the severity of PTSD symptoms, then one-way ANOVA
were conducted. Results: The results revealed 30.4% of the sampled participants
reported stress symptoms equivalent to partial or full PTSD. Posttraumatic growth
was significantly higher in the full and the partial PTSD symptom groups when
compared to the normal group [F (2, 759)=20.534, p<0.001]. At a subscale level,
mature thinking showed a more significant result [F (2,759)=23.146, p<0.001] than
religious growth [F (2, 180.984)=4.811, p<0.01]. Conclusion: The results
indicated a general linear trend between the severity of PTSD symptoms and
posttraumatic growth level, suggesting that indirect trauma also induces both
PTSD symptoms and posttraumatic growth like direct trauma does. The theoretical
implications based on these findings were discussed.
PMID- 29940716
TI - Comparing Attention and Cognitive Function in School Children across Noise
Conditions: A Quasi-Experimental Study.
AB - Objective: The effect of acute noise on cognitive function has long been a topic
of study, yet these effects remain a serious problem for learning performance in
school children. Methods: From November 15, 2010 to December 8, 2010, we enrolled
268 students from three elementary schools (135 boys and 133 girls, 10-12 years
old) in Ulsan, Korea. The study subjects were divided into two groups according
to their test conditions (background versus additional noise), and tests were
conducted using psychological examination tools. Chi-square tests and general
linear models were used to assess the differences of impacts on cognition between
the two groups. Results: After adjusting for socio-demographic covariates, the
noise significantly affected the results of full-scale IQ, verbal IQ, Continuous
Performance Test scores, and Children's Color Trails Test and Stroop test scores.
The groups at high risk of learning difficulties were more affected by noise than
low-risk groups. Conclusion: These findings suggest that noise is hazardous to
the attention and performance of elementary school students, particularly for
groups at greater risk for poor academic achievement. Additional studies are
needed to identify subject-specific levels of noise that can affect attention and
cognitive function.
PMID- 29940717
TI - Long-Term Evolution of Metabolic Status in Patients with Schizophrenia Stably
Maintained on Second-Generation Antipsychotics.
AB - Objective: Second-generation antipsychotics (SGAs) increase the risk of metabolic
syndrome (MetS). Despite the risk of MetS, SGAs may have to be continued with
change in some patients. The aim of this study was to trace the evolution of MetS
in these patients. Methods: Patients with schizophrenia who had been maintained
on a fixed SGA regimen for more than a year were followed-up without changing the
regimen. Metabolic indicators were evaluated at baseline and at follow-up.
Prevalence, incidence and spontaneous normalization rate of MetS were estimated.
Risk factors that might have influenced the evolution were scrutinized. Results:
A total of 151 subjects were included. During the mean observation period of
389.9+/-162.4 days, the prevalence of MetS was increased from 35.1 to 45.0%. The
incidence rate was 29.6%, while the normalization rate was 26.4%, risk factors
affecting incidence were age (OR=1.09, 95% CI: 1.03-1.17), baseline continuous
values of metabolic syndrome risk scores (cMetS, OR=1.77, 95% CI:1.29-2.55) and
baseline body weight (OR=1.06, 95% CI: 1.01-1.13). Normalization was influenced
by age (OR=0.74, 95% CI: 0.57-0.89) and baseline body weight (OR=0.85, 95% CI:
0.72-0.95). Conclusion: The prevalence of MetS steadily increased with the
continuous use of SGAs. However, individual difference was extensive and about a
quarter of the patients were able to recover naturally without specific
measurements.
PMID- 29940718
TI - Should Let Them Go? Study on the Emergency Department Discharge of Patients Who
Attempted Suicide.
AB - Objective: The purpose of this study was to analyze the characteristics and
factors of voluntary discharged patients after suicide attempt and analyze the
effectiveness of follow-up measures. Methods: Total 504 adult patients aged 14
years and over, who visited a local emergency medical center from September 1,
2013 to December 31, 2015 were enrolled and retrospectively reviewed. We analyzed
the relationship with voluntary discharge group (VDG) among basic
characteristics, suicidal attempt variables, outcome variables related to suicide
attempts, and treatment related variables comparing with normal discharge group
(NDG). Results: Of the total 504 suicide attempts, three hundred eleven (61.7%)
patients were VDG and 193 (38.2%) were NDG. The proportion of patients who
completed the community service linkage were 18.7% (36/193) in NDG, compared with
7.7% (24/311) in VDG (p<0.05). In addition, the ratio of the patients who visited
psychiatric outpatient department in NDG were 57.0% (110/193), more than four
times as likely as 14.5% (45/311) in VDG (p<0.05). Conclusion: Over sixty percent
of suicide attempters discharged against medical advice. Further various aspects
of national supportive measures including strengthening case management service
should be considered.
PMID- 29940719
TI - Effects of Atomoxetine on Height and Weight in Korean Children and Adolescents
with Attention-Deficit/Hyperactivity Disorder: A Retrospective Chart Review.
AB - Objective: We aimed to investigate the long-term effects of atomoxetine on growth
in Korean children and adolescents with attention-deficit/hyperactivity disorder
(ADHD). Methods: The medical records of 82 subjects (mean age, 9.0+/-2.0 years;
64 boys) with ADHD treated with atomoxetine for at least 1 year at the Department
of Psychiatry at Asan Medical Center were retrospectively reviewed. Height and
weight data were prospectively obtained and retrospectively gathered and
converted to age- and gender-corrected z scores using norms from Korean youths.
Growth changes were analyzed using random coefficients models with changes in
height or weight z scores as the dependent variables. Results: Height z scores
significantly decreased during the treatment period (beta=-0.054, p=0.024).
Height z scores decreased during the 1st year of treatment (beta=-0.086,
p=0.003), but did not change after the 1st year. Weight z scores did not change
significantly during treatment (beta=0.004, p=0.925). Conclusion: Our results
suggest that long-term atomoxetine treatment may be associated with deficits in
height growth in Korean youths, although this effect was minor and tended to be
attenuated over the first year. Because of the limitations of this study such as
retrospective design and selection bias, further prospective studies are needed.
PMID- 29940720
TI - Effect of antiviral therapy in reducing perinatal transmission of hepatitis B
virus and maternal outcomes after discontinuing them.
AB - Background/Aims: There have been numerous efforts to reduce mother-to-child
transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during
pregnancy. However, there are limited data regarding the outcomes of pregnant
women after delivery. This study was performed to evaluate the efficacy of
antiviral agents in preventing MTCT of HBV and maternal long-term outcomes.
Methods: The HBV-infected pregnant women treated with antiviral agents to prevent
MTCT were retrospectively reviewed. Forty-one pregnant women who received
telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed.
Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants
after 7 months of birth. Eleven mothers were followed >1 year after delivery.
Results: The mean HBV DNA titer before antiviral therapy was 8.67 (6.60-9.49) log
copies/mL, and the median age at delivery was 32 years (range, 22-40). Eleven
patients were treated with tenofovir and 30 with telbivudine. The median duration
was 57 days (range, 23-100), and the median HBV DNA titer at birth was 5.06 log
copies/mL (range, 2.06-6.50). Antiviral treatments were associated with
significant HBV DNA reduction (P<0.001). Among 43 infants (two cases of twins),
HBsAb was not detected in two, subsequently confirmed to have HBV infection.
Biochemical flare was observed in two of 11 mothers followed >12 months, and an
antiviral agent was administered. Conclusions: Antiviral treatment during late
pregnancy effectively reduced MTCT. Long-term follow-up should be required in
such cases. In addition, given that maternal biochemical flare occurred in 18% of
mothers, re-administration of antiviral agents might be required.
PMID- 29940722
TI - Analysis of the Risk Factors for Unfavorable Radiologic Outcomes after Fusion
Surgery in Thoracolumbar Burst Fracture : What Amount of Postoperative
Thoracolumbar Kyphosis Correction is Reasonable?
AB - Objective: The aims in the management of thoracolumbar spinal fractures are not
only to restore vertebral column stability, but also to obtain acceptable
alignment of the thoracolumbar junction (T-L junction) to prevent complications.
However, insufficient surgical correction of the thoracolumbar spine would be
likely to cause late progression of abnormal kyphosis. Therefore, we identified
the surgical factors that affected unfavorable radiologic outcomes of the
thoracolumbar spine after surgery. Methods: This study was conducted in a single
institution from January 2007 to December 2013. A total of 98 patients with
unstable thoracolumbar spine fracture were included. In these patients, fixation
was done through transpedicular screws with rods by three surgical patterns. We
reviewed digital radiographs and analyzed the images preoperatively and
postoperatively during follow-up visits to compare the change of the
thoracolumbar Cobb angle with radiologic parameters and clinical outcomes. The
unfavorable radiologic group was defined as the patients who were measured as
having greater than 20 degrees of thoracolumbar Cobb angle on the last follow-up,
or who underwent kyphotic progression of thoracolumbar Cobb angle greater than 10
degrees from the immediate postoperative state to final follow-up, or who had
overt instrument failure with/without additional surgery. We assessed the risk
factors that affected the unfavorable radiologic outcomes. Results: We had 43
patients with unfavorable radiologic outcomes, including 35 abnormal
thoracolumbar alignments and 14 instrumental failures with/without additional
surgery. The multivariate logistic regression test showed that immediate
postoperative T-L junction Cobb angle less than 10.5 degrees was a statistically
significant risk factor, as well as the presence of osteoporosis (p=0.017 and
0.049, respectively). Conclusion: Insufficient correction of thoracolumbar
kyphosis was considered to be a major factor of an unfavorable radiological
outcome. The spinal surgeon should consider that having a T-L junction Cobb angle
larger than 10.5 degrees immediately after surgery could result in an unfavorable
radiological outcome, which is related to a poor clinical outcome.
PMID- 29940721
TI - Transcanal Endoscopic Ear Surgery for Congenital Cholesteatoma.
AB - OBJECTIVES: As endoscopic instrumentation, techniques and knowledges have
significantly improved recently, endoscopic ear surgery has become increasingly
popular. Transcanal endoscopic ear surgery (TEES) can provide better
visualization of hidden areas in the middle ear cavity during congenital
cholesteatoma removal. We aimed to describe outcomes for TEES for congenital
cholesteatoma in a pediatric population. METHODS: Twenty-five children (age, 17
months to 9 years) with congenital cholesteatoma confined to the middle ear
underwent TEES by an experienced surgeon; 13 children had been classified as
Potsic stage I, seven as stage II, and five as stage III. The mean follow-up
period was 24 months. Recurrence of congenital cholesteatoma and surgical
complication was observed. RESULTS: Congenital cholesteatoma can be removed
successfully via transcanal endoscopic approach in all patients, and no surgical
complications occurred; only one patient with a stage II cholesteatoma showed
recurrence during the follow-up visit, and the patient underwent revision
surgery. The other patients underwent one-stage operations and showed no
cholesteatoma recurrence at their last visits. Two patients underwent second
stage ossicular reconstruction. CONCLUSION: Although the follow-up period and
number of patients were limited, pediatric congenital cholesteatoma limited to
the middle ear cavity could be safely and effectively removed using TEES.
PMID- 29940723
TI - Does the Access Angle Change the Risk of Approach-Related Complications in
Minimally Invasive Lateral Lumbar Interbody Fusion? An MRI Study.
AB - OBJECTIVE: To investigate the potential risk of approach-related complications at
different access angles in minimally invasive lateral lumbar interbody fusion.
METHODS: Eighty-six axial magnetic resonance images were obtained to analyze the
risk of approach-related complications. The access corridor were simulated at
different access angles and the potential risk of neurovascular structure injury
was evaluated when the access corridor touching or overlapping the corresponding
structures at each angle. Furthermore, the safe corridor length was measured when
the corridor width was 18 and 22 mm. RESULTS: When access angle was 0 degrees ,
the potential risk of ipsilateral nerve roots injury was 54.7% at L4-L5. When
access angle was 45 degrees , the potential risk of abdominal aorta,
contralateral nerve roots or central canal injury at L4-L5 was 79.1%, 74.4%, and
30.2%, respectively. The length of the 18mm-wide access corridor was largest at 0
degrees and it could reach 44.5 mm at L3-L4 and 46.4 mm at L4-L5. While the
length of the 22 mm-wide access corridor was 42.3 mm at L3-L4 and 44.1 mm at L4
L5 at 0 degrees . CONCLUSION: Changes in the access angle would not only affect
the ipsilateral neurovascular structures, but also might adversely influence the
contralateral neural elements. It should be also noted to surgeons that
alteration of the access angle changed the corridor length.
PMID- 29940724
TI - Multilevel Percutaneous Vertebroplasty (More than Three Levels) in the Management
of Osteoporotic Fractures.
AB - OBJECTIVE: Percutaneous vertebroplasty (PV) is a minimally invasive procedure
designed to treat various spinal pathologies. The maximum number of levels to be
injected at one setting is still debatable. This study was done to evaluate the
usefulness and safety of multilevel PV (more than three vertebrae) in management
of osteoporotic fractures. METHODS: This prospective study was carried out on
consecutive 40 patients with osteoporotic fractures who had been operated for
multilevel PV (more than three levels). There were 28 females and 12 males and
their ages ranged from 60 to 85 years with mean age of 72.5 years. We had
injected 194 vertebrae in those 40 patients (four levels in 16 patients, five
levels in 14 patients, and six levels in 10 patients). Visual analogue scale
(VAS) was used for pain intensity measurement and plain X-ray films and computed
tomography scan were used for radiological assessment. The mean follow-up period
was 21.7 months (range, 12-40). RESULTS: Asymptomatic bone cement leakage has
occurred in 12 patients (30%) in the present study. Symptomatic pulmonary
embolism was observed in one patient. Significant improvement of pain was
recorded immediate postoperative in 36 patients (90%). CONCLUSION: Multilevel PV
for the treatment of osteoporotic fractures is a safe and successful procedure
that can significantly reduce pain and improve patient's condition without a
significant morbidity. It is considered a cost effective procedure allowing a
rapid restoration of patient mobility.
PMID- 29940725
TI - Photoredox Cyanomethylation of Indoles: Catalyst Modification and Mechanism.
AB - The direct cyanomethylation of indoles at the 2- or 3-position was achieved via
photoredox catalysis. The versatile nitrile synthon is introduced as a radical
generated from bromoacetonitrile, a photocatalyst, and blue LED as a light
source. The mechanism of the reaction is explored by determination of the Stern
Volmer quenching constants. By combining photophysical data and mass spectrometry
to follow the catalyst decomposition, the catalyst ligands were tuned to enable
synthetically useful yields of radical coupling products. A range of indole
substrates with alkyl, aryl, halogen, ester, and ether functional groups
participate in the reaction, affording products in 16-90% yields. The reaction
allows the rapid construction of synthetically useful cyanomethylindoles,
products that otherwise require several synthetic steps.
PMID- 29940726
TI - pH-Responsive Polyion Complex Vesicle with Polyphosphobetaine Shells.
AB - When a bioactive molecule is taken into cells by endocytosis, it is sometimes
unable to escape from the lysosomes, resulting in inefficient drug release. We
prepared pH-responsive polyion complex (PIC) vesicles that collapse under acidic
conditions such as those inside a lysosome. Furthermore, under acidic conditions,
cationic polymer was released from the PIC vesicles to break the lysosome
membranes. Diblock copolymers (P20M167 and P20A190) consisting of water-soluble
zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) block and
cationic or anionic blocks were synthesized via reversible addition-fragmentation
chain transfer (RAFT) radical polymerization. Poly(3-(methacrylamidopropyl)
trimethylammonium chloride) (PMAPTAC) and poly(sodium 6-acrylamidohexanoate)
(PAaH) were used as the cationic and anionic blocks, respectively. The pendant
hexanoate groups in the PAaH block are ionized in basic water and in phosphate
buffered saline (PBS), while the hexanoate groups are protonated in acidic water.
In basic water, PIC vesicles were formed from a charge neutralized mixture of
oppositely charged diblock copolymers. At the interface of PIC vesicle and water
exists biocompatible PMPC shells. Under acidic conditions, the PIC vesicles
collapsed, because the charge balance shifted due to protonation of the PAaH
block. After collapse of the PIC vesicles, P20A190 formed micelles composed of
protonated PAaH core and PMPC shells, while P20M167 was released as unimers. PIC
vesicles can encapsulate hydrophilic nonionic guest molecules into their hollow
core. Under acidic conditions, the PIC vesicles can release the guest molecules
and P20M167. The cationic P20M167 can break the lysosome membrane to efficiently
release the guest molecules from the lysosomes to the cytoplasm.
PMID- 29940727
TI - Orientationally Fabricated Zwitterionic Molecularly Imprinted Nanocavities for
Highly Sensitive Glycoprotein Recognition.
AB - Glycoprotein recognition has recently gained a lot of attention, since
glycoproteins play important roles in a diverse range of biological processes.
Robustly synthesized glycoprotein receptors, such as molecularly imprinted
polymers (MIPs), which can be easily and sustainably handled, are highly
attractive as antibody substitutes because of the difficulty in obtaining high
affinity antibodies specific for carbohydrate-containing antigens. Herein,
molecularly imprinted nanocavities for glycoproteins have been fabricated via a
bottom-up molecular imprinting approach using surface-initiated atom transfer
radical polymerization (SI-ATRP). As a model glycoprotein, ovalbumin was
immobilized in a specific orientation onto a surface plasmon resonance sensor
chip by forming a conventional cyclic diester between boronic acid and cis-diol.
Biocompatible polymer matrices were formed around the template molecule,
ovalbumin, using SI-ATRP via a hydrophilic comonomer, 2-methacryloyloxyethyl
phosphorylcholine, in the presence of pyrrolidyl acrylate (PyA), a functional
monomer capable of electrostatically interacting with ovalbumin. The removal of
ovalbumin left MIPs with binding cavities containing boronic acid and PyA
residues located at suitable positions for specifically binding ovalbumin.
Careful analysis revealed that strict control over the polymer significantly
improved sensitivity and selectivity for ovalbumin recognition, with a limit of
detection of 6.41 ng/mL. Successful detection of ovalbumin in an egg white matrix
was demonstrated to confirm the practical utility of this approach. Thus, this
strategy of using a polymer-based recognition of a glycoprotein through
molecularly imprinted nanocavities precisely prepared using a bottom-up approach
provides a potentially powerful approach for detection of other glycoproteins.
PMID- 29940728
TI - Reaction-Based Color-Convertible Fluorescent Probe for Ferroptosis
Identification.
AB - Ferroptosis is an iron-mediated, caspase-independent pathway of cell death that
is accompanied with the accumulations of reactive oxygen species (ROS) and
oxygenases, as well as being involved in many other pathophysiological
procedures. However, specific and rapid monitoring of ferroptosis in living cells
or tissues has not been achieved so far. Herein, a quinoxalinone-based
fluorescent probe (termed as Quinos-4, or QS-4) with a reactive aromatic
thioether moiety was designed for ferroptosis identification. Upon exposing it to
high levels of ROS and hemeoxygenase-1 (HO-1), which are considered as the
biochemical characteristics of ferroptosis, QS-4 could be oxidized into a
sulfoxide derivative (QSO-4) and its original aggregation-induced enhanced red
fluorescence emission could be converted to green fluorescence emission sharply.
On the basis of this unique reaction-induced color conversion, this molecular
probe can be employed for identifying the occurrence of ferroptosis both in vitro
and in vivo.
PMID- 29940729
TI - Control of Electron Flow Direction in Photoexcited Cycloplatinated Complex
Containing Conjugated Polymer-Single-Walled Carbon Nanotube Hybrids.
AB - Conjugated polymers incorporated with cycloplatinated complexes (P1-Pt and P2-Pt)
were used as dispersants for single-walled carbon nanotubes (SWCNTs). Significant
changes in the UV-vis absorption spectra were observed after the formation of the
polymer/SWCNT hybrids. Molecular dynamics (MD) simulations revealed the presence
of a strong interaction between the cycloplatinated complex moieties and the
SWCNT surface. The photoinduced electron transfer processes in these hybrids were
strongly dependent on the type of the comonomer unit. Upon photoexcitation, the
excited P1-Pt donates electrons to the SWCNT, while P2-Pt accepts electrons from
the photoexcited SWCNT. These observations were supported by results from Raman
and femtosecond time-resolved transient absorption spectroscopy experiments. The
strong electronic interaction between the Pt complexes and the SWCNT gives rise
to a new hybrid system that has a controllable photoinduced electron transfer
flow, which are important in regulating the charge transport processes in SWCNT
based optoelectronic devices.
PMID- 29940730
TI - Redox Active Quinoidal 1,2,4-Benzotriazines.
AB - Modifying the para-quinonimine 1,3-diphenyl-1,2,4-benzotriazin-7(1 H)-one (2a) (
E1/2-1/0 -1.20 V), by replacing the N1-phenyl by pentafluorophenyl, the C3-phenyl
by trifluoromethyl, or the C7 carbonyl by ylidenemalononitrile, led to improved
electron affinities as determined by cyclic voltammetry and computational
studies. Combining structural changes further improved electron accepting
abilities: the most electron deficient analogues ( E1/2-1/0 ~ -0.65 V) involved
combining the ylidenemalononitrile groups at C7 with the trifluoromethyl groups
at C3. 1,2,5-Thiadiazolo fusion at C5-C6 did not affect the redox behavior but
did enhance the UV-vis absorption profile. During the synthesis of the
thiadiazolo analogues, 1,4-thiazino-fused analogues 6 were obtained in low yield,
which thermally ring contract to the triazafluoranthenones 7. Compounds are fully
characterized, and X-ray data are provided for selected analogues.
PMID- 29940731
TI - A Dual-Modal Molecular Probe for Near-Infrared Fluorescence and Photoacoustic
Imaging of Peroxynitrite.
AB - Peroxynitrite (ONOO-), a reactive and short-lived biological oxidant, is closely
related with many pathological conditions such as cancer. However, real-time in
vivo imaging of ONOO- in tumors remains to be challenging. Herein, we develop a
near-infrared fluorescence (NIRF) and photoacoustic dual-modal molecular probe
(CySO3CF3) composed of a water-soluble hemicyanine dye caged with a
trifluoromethyl ketone moiety for in vivo imaging of ONOO-. The trifluoromethyl
ketone moiety can undergo a series of ONOO--induced cascade oxidation-elimination
reactions, leading to sensitive and specific fluorescence and photoacoustic turn
on responses toward ONOO-; whereas, a zwitterionic structure of the hemicyanine
component ensures good water-solubility. Thus, CySO3CF3 not only specifically
detects ONOO- in solution and cells with the limit of detection down to 53 nM but
also allows for NIRF and photoacoustic dual-modal imaging of ONOO- in the tumors
of living mice.
PMID- 29940732
TI - Land Use Controls on the Spatial Variability of Dissolved Black Carbon in a
Subtropical Watershed.
AB - Rivers export roughly 250 Pg of dissolved organic carbon (DOC) to coastal oceans.
DOC exported from rivers can be a reflection of watershed dynamics, and changes
in land use can lead to shifts in the molecular composition and reactivity of
riverine DOC. About 10% of DOC exported from rivers is dissolved black carbon
(DBC), a collection of polycondensed aromatic compounds derived from the
incomplete combustion of biomass and fossil fuels. While DOC and DBC export are
generally coupled, the effects of watershed land use on DBC quality are not well
understood. In this study, DBC samples were collected throughout the Altamaha
River watershed in Georgia, USA. DBC was characterized using the
benzenepoly(carboxylic acid) method and Fourier transform ion cyclotron resonance
mass spectrometry (FTICR-MS). DBC had a more polycondensed character in areas of
the watershed with less anthropogenic disturbance. Furthermore, FTICR-MS revealed
that DBC became enriched with a lower molecular weight, heteroatomic signature in
response to higher anthropogenic activity. As global land cover continues to
change, this study demonstrates on a localized scale that watershed land use can
influence the export and composition of DBC, which may have further implications
for global carbon and nutrient cycling.
PMID- 29940733
TI - High-Throughput Screening Approach for the Optoelectronic Properties of
Conjugated Polymers.
AB - We propose a general high-throughput virtual screening approach for the optical
and electronic properties of conjugated polymers. This approach makes use of the
recently developed xTB family of low-computational-cost density functional tight
binding methods from Grimme and co-workers, calibrated here to (Time-Dependent)
Density Functional Theory ((TD)DFT) data computed for a representative diverse
set of (co)polymers. Parameters drawn from the resulting calibration using a
linear model can then be applied to the xTB derived results for new polymers,
thus generating near DFT-quality data with orders of magnitude reduction in
computational cost. As a result, after an initial computational investment for
calibration, this approach can be used to quickly and accurately screen on the
order of thousands of polymers for target applications. We also demonstrate that
the (opto)electronic properties of the conjugated polymers show only a very minor
variation when considering different conformers and that the results of high
throughput screening are therefore expected to be relatively insensitive with
respect to the conformer search methodology applied.
PMID- 29940734
TI - Formaldehyde Controlling the Synthesis of Multishelled SiO2/Fe xO y Hollow Porous
Spheres.
AB - A concise and facile sol-gel method to prepare multiple magnetic SiO2/Fe xO y
hollow porous spheres was developed. A series of SiO2/Fe xO y hollow porous
spheres consisting of single shell, yolk-shell, double shells, and triple shells
could be obtained by simply adjusting the formaldehyde amount, as Fe(acac)3 was
used as the shell-forming promoter. As the formaldehyde amount increases, the
morphology of the as-prepared hollow spheres changed from single-shelled, yolk
shelled, double-shelled, to triple-shelled and then turned back. The spheres
possess a large specific surface area (~966 m2/g), uniform mesopores (~4.5 nm),
and large pore volume (1.37 cm3/g). Moreover, the yolk-shelled spheres have been
successfully used in in situ adsorbing and reducing heavy metal ions in aqueous
solution; the results suggested that it was an efficient adsorbent and convenient
to concentrate from water.
PMID- 29940735
TI - Instant Strong Adhesive Behavior of Nanocomposite Gels toward Hydrophilic Porous
Materials.
AB - We investigated the adhesion behavior of nanocomposite hydrogels (NC gels),
consisting of unique organic (polymer)-inorganic (clay) network structures,
toward inorganic and organic materials. The NC gels exhibit instant and strong
adhesion to inorganic and organic substrates with hydrophilic porous surfaces.
The NC gels instantly adhere to hydrophilic porous substrates (e.g., unglazed
ceramic surfaces and polymer membranes) through simple light contact. In
addition, a small piece of NC gel effectively joined two substrate samples (e.g.,
concrete blocks and bricks) through lamination of the interposing NC gel. The
resulting conjoined materials were unable to be separated at the gel-substrate
interface; rather, the gel itself fractured upon separation, which indicates that
the adhesive strength at the interface is greater than the tensile strength of
the NC gel. With the exception of NC gels with very high clay concentrations (
Cclay's), instant strong adhesion and cohesive failure by subsequent stretching
were observed for almost all NC gels composed of different polymers or different
Cclay values. A thermoresponsive NC gel was reversibly adhered and could be
peeled from the surface by stretching (adhesive failure) at a temperature above
its transition temperature. The mechanism of instant strong adhesion or
reversible adhesion is discussed based on dangling chains that exist on the
surfaces of the NC gels composed of polymer-clay networks. The cut surface of an
NC gel generally exhibited a higher adhesive strength than the as-prepared
surface because of longer dangling chains.
PMID- 29940736
TI - Probing Metal-Organic Framework Design for Adsorptive Natural Gas Purification.
AB - Parent and amine-functionalized analogues of metal-organic frameworks (MOFs), UiO
66(Zr), MIL-125(Ti), and MIL-101(Cr), were evaluated for their hydrogen sulfide
(H2S) adsorption efficacy and post-exposure acid gas stability. Adsorption
experiments were conducted through fixed-bed breakthrough studies utilizing
multicomponent 1% H2S/99% CH4 and 1% H2S/10% CO2/89% CH4 natural gas simulant
mixtures. Instability of MIL-101(Cr) materials after H2S exposure was discovered
through powder X-ray diffraction and porosity measurements following adsorbent
pelletization, whereas other materials retained their characteristic properties.
Linker-based amine functionalities increased H2S breakthrough times and
saturation capacities from their parent MOF analogues. Competitive CO2 adsorption
effects were mitigated in mesoporous MIL-101(Cr) and MIL-101-NH2(Cr), in
comparison to microporous UiO-66(Zr) and MIL-125(Ti) frameworks. This result
suggests that the installation of H2S binding sites in large-pore MOFs could
potentially enhance H2S selectivity. In situ Fourier transform infrared
measurements in 10% CO2 and 5000 ppm H2S environments suggest that framework
hydroxyl and amine moieties serve as H2S physisorption sites. Results from this
study elucidate design strategies and stability considerations for engineering
MOFs in sour gas purification applications.
PMID- 29940737
TI - Mixed-Charged Zwitterionic Polymeric Micelles for Tumor Acidic Environment
Responsive Intracellular Drug Delivery.
AB - A new class of mixed-charged zwitterionic copolymer poly(aminoethyl methacrylate)
co-poly(methacrylic acid)- co-poly( n-butyl methacrylate) (CPMA) was prepared as
drug nanocarrier for efficient intracellular delivery of Doxorubicin (DOX). The
mixed-charged CPMA copolymer could readily assemble to micelles in physiological
environment (pH 7.4) with the size of 42.6 nm and zeta potential of -26 mV, which
would lead to a prolonged circulation time and enhanced tumor penetration.
However, the micelles formed large aggregates due to the protonation of carboxyl
groups at extracellular tumor pH (pH 6.5). Meanwhile, the zeta potential of CPMA
micelles increased from -26 mV to -6 mV when the solution pH was changed from pH
7.4 to pH 6.5. The increase of size and zeta potential at extracellular tumor pH
could benefit the retention of micelles in tumor matrix and uptake by cancer
cells. The DOX-loaded mixed-charged CPMA micelles could induce a higher
internalization at pH 6.5 than 7.4 at varied time periods. Moreover, cytotoxicity
assay demonstrated that the blank micelles showed excellent biocompatibility, but
were highly cytotoxic toward KB cells after loading with DOX. Thus, the mixed
charged zwitterionic polymeric micelles might be a promising carrier for tumor
acidic environment responsive drug delivery.
PMID- 29940738
TI - Demonstration of a Novel Charge-Free Reverse Wormlike Micelle System.
AB - We demonstrate a novel charge-free reverse wormlike micelle (RWLM) consisting of
a ternary mixture of a nonionic amphiphilic block copolymer, fatty acid alkyl
ester oil, and water under ambient conditions. Nonionic amphiphile tetra
[poly(oxyethylene)-poly(oxybutylene)]pentaerythrityl ether (TEBPE) self-assembled
into spheroid-type micelles in nonaqueous media isopropyl myristate (IPM) with
viscosity comparable to that of IPM. The addition of water increases viscosity
only slightly up to a certain concentration of water and then drastically,
demonstrating the sphere-to-wormlike micelle transition as confirmed by small
angle X-ray scattering. Further increase in water decreases the viscosity after
attaining a maximum value. The zero shear viscosity (eta0) of the 10 wt %
TEBPE/IPM system reached the maximum at 2.6 wt % water and ca. 56 Pa.s, which is
~fivefold higher than that of water. Dynamic rheological measurements on the
highly viscous solutions confirmed the viscoelastic behavior and could be
described by the Maxwell model. Conductivity, measured in the presence of a
conductive probe, 1-ethyl-3-methylimidazolium tetrafluoroborate, was found to be
higher for viscous samples compared to the nonviscous samples, suggesting the
static percolation caused by the RWLM formation. Decrease in eta0 and
conductivity beyond a maximum suggests the shortening of reverse micelles. A
similar behavior has been observed in other fatty acid alkyl ester oils of
different alkyl chain lengths. Note that most of the RWLM systems previously
reported are based on phosphatidylcholine (PC). Formulation and structure
properties related to non-PC-based RWLMs have been rarely explored. Non-PC-based
RWLMs using chemically stable and low-cost synthetic molecules can be applied not
only in pharmaceuticals and cosmetics but also in a wide range of applications
including drag reduction agents for nonaqueous fluids and as a template for
nanomaterial synthesis.
PMID- 29940739
TI - Impact of Humidity on Silica Nanoparticle Agglomerate Morphology and Size
Distribution.
AB - The effect of humidity on flame-made metal oxide agglomerate morphology and size
distribution is investigated, for the first time to our knowledge, and compared
to that on soot, which has been widely studied. Understanding the impact of
humidity on such characteristics is essential for storage, handling, processing,
and eventual performance of nanomaterials. More specifically, broadly used
agglomerates of flame-made silica nanoparticles are humidified at various
saturation ratios, S = 0.2-1.5, and dried before characterization with a
differential mobility analyzer (DMA), an aerosol particle mass (APM) analyzer,
and transmission electron microscopy. At high humidity, the constituent single
and/or aggregated (chemically bonded) primary particles (PPs) rearrange to
balance the capillary forces induced by condensation-evaporation of liquid
bridges between PPs. Larger agglomerates restructure more than smaller ones,
narrowing their mobility size distribution. After humidification at S = 1.5 and
drying, agglomerates collapse into compact structures that follow a fractal
scaling law with mass-mobility exponent Dfm = 3.02 +/- 0.11 and prefactor km =
0.27 +/- 0.07. This critical S = 1.5 for silica agglomerates is larger than the
1.26 obtained for soot because of the hydrophilic surface of silica that delays
water evaporation. The relative effective density, rhoeff/rho, of collapsed
agglomerates becomes invariant of mobility diameter, dm, similar to that of
fluidized and spray-dried granules. The average silica rhoeff/rho = 0.28 +/- 0.02
is smaller than the 0.36 +/- 0.04 measured for the humidified-dried soot because
of the larger size of silica aggregates, dm/ dp, and number of constituent
primary particles, np, of diameter dp. This is verified by tandem-DMA (TDMA)
measurements, yielding maximum dm = 3 dp or 5 dp and np = 13 or 36 for the soot
or silica aggregates studied here, in good agreement with those reported from
microscopy and high-pressure agglomerate dispersion. A scaling law relating the
initial dm,o to dm, Dfm, and km after condensation-drying is developed. The mass
mobility relationship of collapsed silica and soot agglomerates obtained by
combining this law with fast TDMA measurements is in excellent agreement with
that measured by the direct, but tedious, DMA-APM analysis.
PMID- 29940740
TI - Mutations in Known and Novel cancer Susceptibility Genes in Young Patients with
Pancreatic Cancer.
AB - BACKGROUND: Pancreatic cancer is the fourth most common cause of mortality due to
cancer, globally. It has a poor prognosis and is usually diagnosed at later
stages when tumor resection is not possible. Heritability for pancreatic cancer
is relatively high and clinically significant. METHODS: A group of 24 pancreatic
cancer patients with young age at onset, from a referral hospital in Tehran
University of Medical Sciences were screened for mutations in 710 cancer relevant
genes using next generation sequencing technology. RESULTS: Two patients had
pathogenic mutations in known pancreatic cancer susceptibility genes, BRCA1/2.
Two other patients also had potentially pathogenic mutations in 2 novel candidate
genes including PARP4 and EXO1. CONCLUSION: BRCA1/2 genes are the most commonly
mutated pancreatic cancer susceptibility genes that should be considered in all
pancreatic cancer cases with young age at onset or a family history of cancer.
PARP4 and EXO1 also are potential candidate genes for susceptibility to
pancreatic cancer. Identifying the hereditary cases of pancreatic cancer will
help to offer more targeted treatments to the patients and also to prevent cancer
in family members who might be a mutation carrier.
PMID- 29940741
TI - Evaluation of Mean Platelet Volume in Patients With Behcet's Disease as an
Indicator of Vascular Thrombosis.
AB - BACKGROUND: Patients with Behcet's disease (BD) are recognized with increased
risk for venous and/or arterial thrombosis. Thrombotic tendency of BD is not
known. Vascular injury, loss and dysfunction/hyperfunction of endothelial cells
are believed to play a role in thrombosis development. Injury and inflammation
due to vasculitis can cause platelet response with increase in mean platelet
volume (MPV) and thrombosis in BD. In this study, we aimed to compare the levels
of MPV between patients with BD and healthy controls, and also show its effect on
thrombosis. METHODS: One hundred patients with BD and 100 healthy controls were
evaluated for MPV levels with clinical findings in age-gender matched case
control study. The variables of patients and controls were compared and
correlated using chi-square, Mann-Whitney U and Spearman tests. Logistic
regression analysis was used to determine independent predictors of vascular
involvement and thrombosis. RESULTS: Mean MPV was significantly higher in
patients with BD than healthy controls (MPV; Patients: 9.2 +/- 0.9 [7.3-12.9] vs.
Controls: 8.2 +/- 0.6 [6.8-10.6] fl; P<0.0001). Platelets levels were lower than
controls, but not significantly (236 +/- 52.3 [112-451] vs. 245 +/- 52.8 [141
467] x109 /L, P=0.55). Negative correlation was found between platelet count and
MPV in patients (r = -0.51, P=0.01). Presence of erythema nodosum (EN) and MPV
were determined as predictors for vascular involvement and thrombosis (EN:
P<0.0001, OR [95% CI] = 35.4 [6.3-178.2]; MPV: P<0.0001, OR [95% CI] = 12.8 [4.1
24.3]). CONCLUSION: MPV is a simple measurement for indirect monitoring of
platelet activity and thrombotic potential. MPV and EN may be independent risk
factors for vascular thrombosis in BD. Patients with higher MPV levels and EN in
BD, might have been pursued closely for enhancing thrombosis. We advise to check
the MPV and put the patients on anticoagulation if it is high.
PMID- 29940742
TI - Prevalence and Characteristics of Coronary Artery Anomalies Using Invasive
Coronary Angiography in 6237 Consecutive Patients in a Single Center in Turkey.
AB - BACKGROUND: Coronary artery anomalies (CAAs) include clinically and anatomically
diverse types of congenital heart defects occurring in a complicated spectrum.
The aim of the present study is to describe congenital anomalies of coronary
arteries (CAs) and their variations, and also identify the prevalence of these
anomalies in our center. METHODS: The study included a total of 6237 consecutive
patients. Cine-angiographies and digital data of all patients undergoing coronary
angiography (CAG) were reviewed by at least 2 independent and experienced
observers. The Basic Anatomic Classification method was used to classify patients
with CAAs. RESULTS: Of a total of 6237 patients, 2,313 were females (37.1%) and
3924 (62.9 %) were males. CAAs were detected in 247 out of 6237 patients (3.9%,
95% CI: 3.4-4.4). Of these patients, 48 (19.4%, 95% CI: 14.4-24.2) had absent
left main coronary artery (LMCA), 21 (8.5%, 95% CI: 5-11.9) had anomalous origin
from the appropriate sinus, 23 (9.3%, 95% CI: 5.7-12.9) had anomalous origin from
structures other than appropriate sinus, 31 (12.6%, 95% CI: 8.5-16.6 ) had
anomalous origin from the opposite sinus, 101 (40.9%, 95% CI: 34.8-46.9) had
myocardial bridge, and 23 (9.3%, 95% CI: 5.7-12.9) had a coronary artery fistula.
CONCLUSION: Our study results suggested that the total rate of coronary anomaly
was found much higher than those reported in various invasive angiographic
studies.
PMID- 29940743
TI - Prediction of Arterial Blood Gas Factors from Venous Blood Gas Factors in
Intensive Care Unit Admitted Patients.
AB - BACKGROUND: Blood gas analysis is very important in the patients with respiratory
problems. Arterial puncture may cause complications such as pain, local hematoma,
infection and nerve injury. The procedure itself can be technically difficult. In
contrast, venous sampling is an easier procedure with fewer complications.
Therefore, this study aims to determine the possibility of replacement of venous
blood gas (VBG) values by ABG values in ICU wards admitted patients. METHODS: In
this study, 155 paired blood gas samples collected from patients admitted to ICU
wards in Motahari hospital, Marvdasht, Fars, Iran. Statistical means of blood gas
parameters, including PO2, PCO2, HCO3 and PH have been compared in both, arterial
and venous, blood samples in parallel using paired t-test. RESULTS: Mean
difference of arterial and venous gas parameters, PO2, PCO2 and HCO3 , was
significantly differ. All paired gas parameters in arterial and venous blood
samples were significantly correlated, while this correlation was stronger
between PCO2 and HCO3. CONCLUSION: To predict the arterial blood gas parameters
from VBG parameters, single regression models are of more statistical value
compared to multiple regression models. Defined single regression prediction
models could be used to predict arterial PCO2 and HCO3 , which may reduce
arterial sampling in ICU wards.
PMID- 29940744
TI - 7-Farnesyloxycoumarin Exerts Anti-cancer Effects on a Prostate Cancer Cell Line
by 15-LOX-1 Inhibition.
AB - BACKGROUND: Prostate cancer is one of the leading causes of cancer related deaths
in males worldwide. Overexpression of 15-lipoxygenase-1 (15-LOX-1) enzyme and
high activity of its metabolic pathway is reported to be a driver for prostate
cancer malignancy. Farnesyloxycoumarin derivatives (3f, 4f and 7f) inhibit
lipoxygenase enzyme. We hypothesized that farnesyloxycoumarins may exert an anti
cancer effect on prostate cancer cells due to their 15-LOX-1 inhibitory
potential. METHODS: The enzyme inhibitory activity of 3f, 4f and 7f was initially
evaluated on PC-3 and DU145 prostate cancer cell lines. MTT assay was performed
on cancer cell lines and HFF3 cell line to assess cytotoxicity of the compounds.
The apoptotic morphology of cells after treatments was assessed by DAPI staining
and single cell gel electrophoresis. Propidium iodide staining was also performed
to detect cell cycle variations after treatment. RESULTS: 7f inhibited 15-LOX-1
at IC50=4.3 ug/mL, while 3f and 4f did not show high inhibitory activity. 7f
reduced cell viability in PC-3 cells at IC50=22-31 ug/mL, however, no significant
cytotoxicity was revealed on normal cells. DAPI staining and comet assay
confirmed apoptosis and DNA damage in PC-3 cells after 7f treatment, while flow
cytometry results revealed G1 arrest in PC-3 cells. CONCLUSION: The results are
indicative of a distinctive cytotoxic mechanism for 7f compared to other
coumarins, possibly due to its 15-LOX-1 inhibitory potential. Thus, this compound
is valued for further assessments with the aim of developing a promising targeted
therapy for prostate cancer patients.
PMID- 29940745
TI - Prevalence of Human Immunodeficiency Virus in Iranian Blood Donors: A Systematic
Review and Meta-Analysis.
AB - BACKGROUND: The probability of HIV transmission through contaminated blood and
blood products is eye catching. 5%-10% of blood products are contaminated with
HIV. Therefore, it is essential to provide safe blood supply to prevent
transmission of infectious diseases. Current systematic review and meta-analysis
was conducted to evaluate the weighted prevalence of HIV in Iranian blood donors.
METHODS: This study was reported according to PRISMA checklist for systematic
reviews and meta- analysis. Required data were collected by using key words such
as "HIV", "blood donation" OR "blood donors", "epidemiology" OR "prevalence",
"blood transfusion" and "Iran", in international databases including PubMed,
Scopus, Web of Science, Cochrane, Embase and national databases including
Magiran, IranMedex and Scientific Information Databank. Papers were searched
until December 2017. Cochran's Q test and I2 index were used to assess the
heterogeneity among studies. RESULTS: A total of 49 studies including 5403170
donors entered this meta-analysis. According to analysis, the prevalence of HIV
positive patients among Iran blood donors was estimated 7.9/100000 (95% CI:
0.000052-0.000121%). The highest prevalence was related to the central region of
Iran (11.3/100,000 [95% CI:0.000063-0.0002%]) and Kermanshah province
(49.2/100000 [95% CI:0.000273-0.000888%]) and the lowest prevalence was related
to the eastern region (1/100000 [95% CI:0.000001-0.000072%]) and Khorasan Razavi
province (0.9/100000 [95% CI:0.000001-0.000139%]. CONCLUSION: The overall HIV
prevalence in Iranian blood donors is low and satisfying. However, the high
prevalence in some regions and provinces should be reviewed more meticulously.
PMID- 29940747
TI - Ethical Behavior After an Unethical Publication: Glimpse of Hopes.
PMID- 29940746
TI - In Honor of Dr. Ahmad Fayaz, A Prominent Rabies Researcher.
AB - Dr. Ahmad Fayaz is one of the famous scientists in Iran in the field of rabies,
and the most prominent person in controlling and prevention programs in the
country in recent decades. One of his most important scientific achievements was
introducing a new rabies vaccine produced in human diploid cell cultures to treat
people exposed to rabies infection. Following that, anti-rabies serum therapy and
injection of five doses of the cellular vaccine were entered into WHO protocol.
Dr. Fayaz, as an expert and consultant of WHO, traveled to several countries and
recommended appropriate ways to control rabies. This paper intends to celebrate
his scientific contributions through reviewing his services and researches.
PMID- 29940748
TI - miR-133b acts as a tumor suppressor and negatively regulates EMP2 in glioma.
AB - In recent years, the incidence of neuroglioma (glioma) has trended towards a
younger age-group. Gene therapy has been widely implemented and a growing number
of microRNAs associated with glioma have been identified., Herein, we detected
the expression of micro RNA - miR-133b - in glioma by qPCR and also its effect on
cell viability, survival and apoptosis of in vitro U87 and A172 cells. The
binding effect of miR-133b on epithelial membrane protein-2 (EMP2) was verified
and we then investigated the effect of EMP2 on in vitro glioma cells and tested
the expression of apoptosis related factors after administration of altered miR
133b and EMP2 expressions. We found that miR-133b was down-regulated in glioma
compared to adjacent non-tumorous tissue and also that its over-expression
inhibits cell viability and survival and enhances apoptosis in the U87 and A-172
cells. Moreover, miR-133b effectively binds to EMP2, down-regulates its
expression and negates its normal function. EMP2 normally promotes cell apoptosis
and reduces cell viability and survival while miR-133b over-expression regulates
the expression of apoptotic-associated protein and activates the apoptotic
pathway, thus counteracting EMP2 regulation of opposite expression effects.
Further, miR-133b can be considered a tumor suppressor because of its low
expression and effects on cell apoptosis via down-regulating EMP2 expression and
activating the apoptotic cell pathway in glioma. EMP2 is a risk factor for
glioma, and miR-133b should prove a potential target for glioma clinical
prevention and treatment.
PMID- 29940749
TI - Comparison of autologous hematopoietic cell transplantation performed in tandem
and in disease relapse in multiple myeloma patients.
AB - Multiple myeloma is a malignant hemato-oncological malignancy that affects up to
600 people in the Czech Republic every year. Treatment options are under constant
improvement and the autologous hematopoietic cell transplantation (Tx) remains a
part of treatment protocols. Despite modern drug administration, the autologous
Tx keeps its irreplaceable position and when ensuring two autologous Tx, the
studies confirm a survival time more than twice as long as in non-transplant
patients. However, there are no standardized procedures specifying the period in
between the transplantations in more detail. Within our group, we compared the
total of 66 patients who were administered a double transplant. One group
underwent both planned tandem autologous Tx within a median of six months and
mostly achieved just partial remission (PR) and less after the first transplant
and out of disease progression. The other group only underwent the second Tx
within a median of up to 14 months during a progression period or disease
relapse. Both groups were comparable as far as basic parameters are concerned
(age, type of induction therapy and cytogenetic risk). A significantly better
treatment free survival (TFX) and overall survival (OS) were observed in the
group where tandem Tx was administered. TFS was 18 months and median OS was not
reached for the group of patients who received tandem Tx, while TFS was 10 months
(p=0.04) and median OS was 57 months (p=0.005) for those who received delayed
second Tx. In the group of patients who received second Tx during relapse, we
observed that TFS and OS were shorter in those with a higher paraprotein level,
thus suggesting the potential role of paraprotein level as a prognostic marker.
The TFS in the subgroup with a high initial level was 4 months vs. 11 months
(p=0.0016) and OS 44 months vs. 65 months (p=0.03).
PMID- 29940750
TI - Alpha1,2-fucosyl transferase gene, the key enzyme of Lewis y synthesis, promotes
Taxol resistance of ovarian carcinoma through apoptosis-related proteins.
AB - We aimed to investigate the role of FUT1 gene in Taxol resistance and to explore
its mechanism in epithelial ovarian cancer. Three ovarian cancer cell lines, ES
2, SK-OV-3 and OVCAR-3 were selected from epithelial ovarian cancer in this
experiment. Western blot was used to validate the protein expression level of
FUT1 and the apoptosis proteins. The expression level of the corresponding
carrier was validated by RT-PCR. Transfection and isolation of stable
transfectants were carried out to establish the cell line models. The different
concentrations of Taxol on the inhibition of cell growth rate was measured by
MTT, in which Taxol resistance profiling in ovarian cancer cells was determined
by IC50 data. Flow cytometry was conducted to compare cell apoptosis ability.
Caspase-3 activity and the apoptosis proteins were measured by colorimetry and
western blot, respectively, to further compare the cell apoptosis ability in
different groups. To demonstrate the inhibition of miR-FUT1 combined with Taxol
therapy against ovarian cancer, xenograft assay was carried out for the in vivo
effect. The western blot results indicate that FUT1 is expressed in all of the
ovarian cancer cells with different expression level: ES-2 > SK-OV-3 > OVCAR-3.
Besides, FUT1 siRNA was used in the maximum expression of FUT1 cell line ES-2, or
over-expression plasmid was used in the minimum expression of FUT1 cell line
OVCAR-3, to establish stable expression cell lines. After the treatment with
Taxol, the inhibition rate of Taxol was obviously decreased with the established
cell model above, and the IC50 level was significantly increased in the FUT1 over
expression + Taxol group (p Keywords: FUT1, Lewis y, Taxol resistance, ovarian
cancer, apoptosis.
PMID- 29940751
TI - MACC1 silencing inhibits cell proliferation and induces cell apoptosis of lung
adenocarcinoma cells through the beta-catenin pathway.
AB - It has been documented that over-expression of metastasis-associated in colon
cancer-1 (MACC1) is related to poor prognosis in non-small cell lung cancer
(NSCLC). This study investigates the function and underlying molecular mechanisms
of MACC1 in lung adenocarcinoma. Here, we firstly employed immunohistochemistry,
western blotting, real-time PCR, and online database to demonstrate that MACC1
expression was elevated in tumor tissues compared with tumoradjacent or normal
tissues. Real-time PCR, CCK-8, colony formation western blotting, Hoechst
staining, and flow cytometry assays then evaluated the effects of MACC1 knockdown
on the cell cycle, cell proliferation and apoptosis in A549 and H1299
adenocarcinoma cells. Result highlighted that MACC1 knockdown inhibited cell
proliferation, induced G0/ G1 phase arrest and promoted cell apoptosis in vitro.
Mechanistic analysis revealed it also up-regulated expression levels of bax,
cleaved-caspase-3 and cleaved-PARP while down-regulating cyclin D1, c-myc, bcl-2,
and beta-catenin expression in A549 cells. Intriguingly, up-regulation of beta
catenin suppressed G0/G1 phase arrest and apoptosis in MACC1-silenced A549 cells
and this was accompanied by increased levels of cyclin D1, c-myc, and bcl-2.
Collectively, our results indicate that MACC1 knockdown effectively inhibited
cell proliferation and promoted apoptosis of lung adenocarcinoma cells by
regulating the beta-catenin pathway.
PMID- 29940752
TI - Anticancer effect of YWHAZ silencing via inducing apoptosis and autophagy in
gastric cancer cells.
AB - YWHAZ (14-3-3zeta) has been reported to be a prognostic marker for various tumors
and play a crucial role in many oncogenic processes, including proliferation,
migration and invasion. However, the functional role and mechanism of YWHAZ in
gastric cancer (GC) are not in detail and still remain to be studied. In the
present study, the endogenous expression of YWHAZ in gastric cancer cell line BGC
823 was silenced by YWHAZ-specific short hairpin RNA (shRNA). Our data showed
that YWHAZ silencing resulted in cell cycle arrest in BGC-823 cells. Further,
YWHAZ-silenced BGC-823 cells acquired increased apoptosis rate, which was
confirmed by increased levels of cleaved caspase-3, cleaved PARP, and Bax, and
decreased level of Bcl-2. Suppression of YWHAZ also promoted autophagy,
confirming by the upregulation of LC3II /LC3I ratio, and downregulation of p62
level. Moreover, YWHAZ suppression inhibited the activation of PI3K/AKT/mTOR
signaling pathway in BGC-823 cells. LY294002 (PI3K/AKT inhibitor, 200 nM) further
promoted YWHAZ silencing-induced apoptosis and autophagy in BGC-823 cells, while
insulin-like growth factor-1 (IGF-1; PI3K/AKT agonist, 10 ng/ml) had the opposite
role. Finally, suppression of YWHAZ inhibited the growth of the xenograft tumor
in vivo. This study provides extended evidence that YWHAZ can be a potential
therapeutic target for GC.
PMID- 29940753
TI - Expression of autophagy genes in acute myeloid leukemia: associations with
clinical characteristics and prognosis.
AB - The relationships between autophagy-associated gene expression and clinical
characteristics and prognosis in acute myeloid leukemia (AML) have not been well
revealed. We examined mRNA expression of Bcl-2, p62, Beclin 1, VPS34, Rubicon,
ALFY, UVRAG, ULK1, LC3 and NBR1 in 20 AML cases and 10 benign hematological cases
by real-time PCR. Clinical information, treatment responses and outcomes of the
AML patients were collected. Beclin 1, LC3, UVRAG, Rubicon and NBR1 were
downregulated in AML patients compared with control group (P<0.05). Low ULK1
expression was associated with high white blood cell counts (P<0.05). Autophagy
associated gene expression was not correlated with chemotherapy response.
Finally, we analyzed overall survival and found no obvious association with gene
expression. However, in unfavorable outcome patients, low Beclin 1 and p62
expression showed worse overall survival than high-expression. Autophagy genes
are associated with outcome in AML patients and may be biomarkers or targets in
the future.
PMID- 29940754
TI - Breast self-examination in Greek midwives and midwifery students.
AB - The aim of this study is to assess breast self-examination (BSE) practice in a
representative sample of Greek midwives and midwifery students. Breast self
examination (BSE) is infrequent in healthcare professionals, including physicians
and nurses. All midwives (n=245) and graduating midwifery students (n=165) who
attended a congress of midwives were eligible to participate in the study, and a
self-administered, anonymous questionnaire was developed to assess BSE practice.
Midwives performed BSE more frequently than students (p<0.001). In addition,
27.0% of students performed BSE less frequently than every year whereas the
midwives' rate is 14.0% (p<0.001). The proportion of subjects searching for
specific signs of breast cancer during BSE and the BSE technique did not differ
between midwives and students. In midwifery students, higher perceived knowledge
of breast cancer-related issues was associated with more frequent BSE. Only a
minority of Greek midwives and midwifery students practice BSE every month, and
therefore implications for nursing management in BSE education should be included
in midwifery school curricula to ensure increased BSE frequency, improved BSE
accuracy and the promotion of BSE teaching to patients.
PMID- 29940755
TI - Aclidinium bromide inhibits human glioma cell proliferation, migration and
invasion and promotes apoptosis via the PI3K/AKT signaling pathway.
AB - This study investigates the anti-cancer potential of Aclidinium bromide (INN) in
glioblastoma. Glioblastoma cell lines U251 and U87 were treated with INN and its
effects on cell migration and invasion were assessed by transwell migration and
invasion assays., The effects of INN on proliferation and apoptosis were detected
by CCK-8 kit and flow cytometry, and Western blotting determined anti-apoptotic
proteins and signaling pathway changes. The results show that INN effectively
suppressed proliferation, migration and invasion and induced apoptosis in U251
and U87 cells, respectively. Furthermore, the expression levels of the Bcl-2 anti
apoptotic protein was significantly decreased while Bax and caspase-3 expression
were both increased in glioblastoma cells (all, p<0.05). Moreover, INN
inactivated the PI3K/AKT signaling pathway by down-regulating the level of p-AKT,
p-mTOR, P70 and CyclinD1 (all, p<0.05). In conclusion, our data suggests that INN
could provide novel anticancer therapy in the treatment of glioblastoma.
PMID- 29940756
TI - Knockdown of long noncoding RNA CCAT1 inhibits cell growth, invasion and
peritoneal metastasis via downregulation of Bmi-1 in gastric cancer.
AB - Long noncoding RNA colon cancer-associated transcript 1 (lncRNA CCAT1) is highly
expressed in gastric cancer (GC) tissues compared with normal counterparts and
CCAT1 upregulation can promote proliferation and migration of GC cells in vitro.
B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) expression is
positively correlated with tumor progression. The present study aimed to
investigate the biological functions of CCAT1 and the relationships between CCAT1
and Bmi-1 in GC progression. In the present study, CCAT1 was knocked down by
specific shRNA transfection in two human GC cell lines (MGC-803 and SGC-7901).
The effects of CCAT1 knockdown on GC cell proliferation, cell cycle, migration
and invasion were investigated in vitro. The effect of CCAT1 knockdown on
peritoneal metastasis was assessed in nude mice. Bmi-1 expression levels were
examined both in vitro and in vivo. The results showed that CCAT1 knockdown
markedly inhibited cell proliferation, migration and invasion, arrested the cell
cycle at G0/G1 phase in vitro, and inhibited peritoneal metastasis in nude mice,
along with the downregulation of Bmi-1. Taken together, CCAT1 is functionally
involved in growth and metastasis of GC cells and it may be a potential target
for GC therapy.
PMID- 29940757
TI - MicroRNA-548-3p and MicroRNA-576-5p enhance the migration and invasion of
esophageal squamous cell carcinoma cells via NRIP1 down-regulation.
AB - Nuclear receptor interacting protein (NRIP1), also known as RIP140, is a
transcriptional co-regulator required for the maintenance of energy homeostasis
and ovulation. Although several studies have identified roles for NRIP1 in
various cell processes, the biological functions of NRIP1 in esophageal squamous
cell carcinoma (ESCC) remain unknown. Herein, we demonstrate that NRIP1 inhibits
the migration and invasion of ESCC cells. Further mechanistic studies revealed
that NRIP1 is directly targeted by miR-548-3p and miR-576-5p. We then identified
that miR-548-3p and miR-576-5p regulate the migration and invasion of ESCC cells
by inhibiting NRIP1 expression. Interestingly, the expression of miR-548-3p and
miR-576-5p in ESCC cell lines and ESCC tissues is up-regulated and NRIP1 is down
regulated relative to controls. A statistically significant inverse association
was found between the expression levels of miR-548-3p/miR-576-5p and NRIP1. These
combined results reveal novel functions for miR-548-3p, miR-576-5p, and NRIP1 in
regulating ESCC cell migration and invasion which are important functions for the
metastatic process in esophageal cancer.
PMID- 29940758
TI - Adjuvant chemotherapy provided survival benefit for stage T2N0 gastric cancer
with high-risk factors.
AB - The value of adjuvant chemotherapy in T2N0 gastric cancer (GC) remains
controversial. The aim of this retrospective study is to define a high-risk
subgroup of pathological T2N0 GC patients and examine the impact of adjuvant
chemotherapy on overall survival (OS). A total of 225 patients underwent R0
resection for T2N0 gastric adenocarcinoma between 2002 and 2012 and 51/225
(22.7%) of these received adjuvant chemotherapy. Multivariate Cox regression
identified tumor location in the Upper1/3 of the stomach (peast one of the
independent risk factor listed above, and we found that adjuvant chemotherapy
significantly improved OS for this subgroup.
PMID- 29940759
TI - Retreatment with lenalidomide is an effective option in heavily pretreated
refractory multiple myeloma patients.
AB - The combination of lenalidomide and dexamethasone is the current gold standard
for treatment of relapsed multiple myeloma. This study analyzes the efficiency of
repeated lenalidomide treatment in patients with relapsed and refractory multiple
myeloma. A total of 41 patients were prospectively evaluated at the University
Hospital Brno. Lenalidomide was administered at standard dosing and in
combination with corticosteroids and/or chemotherapy. The maximum cumulative dose
of lenalidomide was limited to 4,200 mg because of Czech health insurance rules.
Before the second lenalidomide treatment, all patients were refractory to the
last treatment; previously, 95% of patients had bortezomib treatment, 48% had
autologous transplantation and the median number of prior therapy lines was
three. A partial 14.2% or better response was achieved with the second
lenalidomide treatment. The median progression-free survival was 4.8 months, and
median overall survival was 11.9 months. Unfortunately, predicting risk factors
in lenalidomide retreatment proved unsuccessful. Although our treatment results
were significantly affected by limited Czech health care system coverage for
lenalidomide, we established that its repeated treatment is an effective
therapeutic alternative for heavily pretreated patients with relapsed and
refractory multiple myeloma.
PMID- 29940760
TI - Long non-coding RNA DANCR facilitates glioma malignancy by sponging miR-33a-5p.
AB - Glioma is among the most fatal brain tumors characterized by a highly malignancy
and rapid progression and early metastasis. Dysregulation of long non-coding RNA
differentiation antagonizing non-protein coding RNA (LncRNA DANCR) is associated
with the development, progression and metastasis of various cancers. In the
present study, we investigated functional role of LncRNA DANCR in the malignancy
of glioma. The results showed that LncRNA DANCR was increased in glioma tissues
and cells compared with normal brain tissues and cells. DANCR expression was
positively correlated with the malignancy and poor prognosis of glioma patients.
DANCR contained a binding site of miR-33a-5p. miR-33a-5p was decreased in glioma
tissues and cells compared with normal brain tissues and cells. Downregulation of
miR-33a-5p was positively correlated with the malignancy and poor prognosis of
glioma patients. In glioma tissues, the expression of DANCR was negatively
correlated with the expression of miR-33a-5p. Downregulation of DANCR increased
miR-33a-5p expression. miR-33a-5p mimic reduced the luciferase of DANCR-WT but
not DANCR-MUT. DANCR pull-down showed the expression of miR-33a-5p. miR-33a-5p
mimic enhanced knockdown of DANCR -induced inhibition of cell proliferation,
migration, and EMT, and increase of apoptosis. Anti-miR-33a-5p reversed the
effects of si- DANCR on cell malignancy. Knockdown of DANCR remarkably reduced
the increase of tumor volumes in xenograft mouse models. In tumor tissues,
knockdown of DANCR increased the expression of miR-33a-5p, reduced EMT and
increased apoptosis. Our study provides novel insights in the functions of LncRNA
DANCR-miR-33a-5p axis in tumorigenesis of glioma.
PMID- 29940761
TI - Overexpression of EPS8L3 promotes cell proliferation by inhibiting the
transactivity of FOXO1 in HCC.
AB - The homology of epidermal growth factor receptor pathway substrate 8 (EPS8),
EPS8L3, is elevated significantly in hepatocellular carcinoma (HCC) tissues and
cell lines compared with the normal liver tissues and cell lines. The MTT and
colony formation assays demonstrated that overexpressing EPS8L3 enhances, while
silencing reduces the proliferation of HCC cells. Further experiments illustrated
that overexpressing EPS8L3 promotes the expression of p-AKT, Cyclin D1, but
inhibits the transcriptional activity of FOXO1. Besides, colony formation assay
demonstrated that AKT inhibitor suppresses the effect of EPS8L3 on proliferation
in EPS8L3-overexpressing cells, whereas AKT restores the proliferation of EPS8L3
silenced cells, suggesting that EPS8L3 might promote proliferation by
hyperactivating the AKT signaling pathway and subsequently inhibiting the FOXO1
transcriptional activity. Our results provide new view between EPS8L3 and
progression of human HCC, suggesting that EPS8L3 may be a novel therapeutic
target for HCC.
PMID- 29940762
TI - Epigenetics: an alternative pathway in GISTs tumorigenesis.
AB - Many diseases have different pathological backgrounds responsible for abnormal
cell behavior and exhibiting altered function and signal transduction. This is
especially true for tumors and although changes affecting DNA sequence,
irreversible mutations and chromosomal aberrations in gastrointestinal stromal
tumors (GISTs) have been widely studied, the importance of reversible epigenetic
changes increasingly recognized in many cancers has received insufficient
attention in these tumors. Epigenetic mechanisms are part of normal development
and gene expression under normal conditions, but malfunction of these processes
leads to malignant transformation by disturbing both intra- and intercellular
communication. GISTs are a specific group of gastrointestinal tract tumors
resistant to conventional chemotherapy and radiotherapy. Although they account
for only 1% to 2% of tumors, they are among the most widespread gastrointestinal
mesenchymal tumors. DNA hyper/hypomethylation overexpression/underexpression of
miRNAs or abnormal histone modification may provide an alternative to the genetic
modifications responsible for GIST pathology, response to treatment, prognosis
and overall survival. This review summarizes the known epigenetic mechanisms
involved in GIST pathogenesis; including onset, progression, and GISTs
resistance. Reversible epigenetic changes are a novel and appropriate approach to
halt the spread of metastases and the emergence of resistance in GIST treatment,
and these changes depend on the type of epigenetic alternation, including
inhibitors of histone acetyltranferase and deacetylase and DNA
methyltransferases.
PMID- 29940763
TI - Regorafenib therapy in metastatic colorectal cancer patients: markers and outcome
in an actual clinical setting.
AB - The oral multikinase inhibitor regorafenib had beneficial effects in randomized
clinical phase III trials compared to the placebo in patients with metastatic
colorectal cancer (mCRC) who progressed on standard therapies. The factors which
influence regorafenib response and therapy sequence during treatment history are
still highly discussed, and herein we analyzed the therapy algorithm, outcome and
clinical markers following regorafenib application in a single center register
study. Clinical data for 48 metastatic colorectal cancer patients were collected
from 01.01.2013 to 31.12.2016. Treatment effects according to various patient and
tumor characteristics were evaluated using univariate and multivariate Cox
proportional hazard regression models. The 48 patients comprised 14 (29%) females
and 34 (71%) males, with mean age 64.2+/-9 and ECOG 0-1. Progression free
survival under regorafenib therapy was 2.9 months (quartiles 2.2; 4.4) and the
overall response rate was 2 (4%) and disease control rate was 19 (40%). Overall
survival (OS) and progression free survival (PFS) were investigated under
regorafenib in the chemotherapy regimen given immediately before and afterthis
treatment. Variables including tumor localization, Ras status, CEA and CA 19-9
plasma levels were analyzed for their impact on PFS, and the regorafenib-related
adverse events were also observed. Our study confirms the efficacy of regorafenib
in a real-life setting. We established that response rate and PFS in regorafenib
treatment are independent of tumor localization, Ras status or biomarkers such as
CEA and CA 19-9. Trifluridin/tripacil application or re-induction of chemotherapy
+/- target therapy was effective following regorafenib therapy.
PMID- 29940764
TI - miR-129-5p suppresses breast cancer proliferation by targeting CBX4.
AB - Deregulation of microRNA (miRNA) is closely related to cancer development and
progression. Our previous study identified that miR-129-5p suppresses
proliferation and metastasis in breast cancer cells. Herein, we determined that
CBX4 is a miR-129-5p target gene. CBX4 is up-regulated in breast cancer tissues
and while its over-expression promotes cell proliferation, its knockdown
suppresses cell proliferation in breast cancer cells. Furthermore, CBX4 mediates
miR-129-5p-induced inhibition of cell proliferation and negatively correlates
with the expression of miR-129-5p expression. These combined results suggest that
CBX4 is an oncogene in breast cancer cells, and that it may provide a novel
therapeutic strategy for breast cancer treatment.
PMID- 29940765
TI - Complications and mortality of surgical therapy for esophageal cancer: 10 years
single center experience.
AB - A single-center retrospective study the complication and mortality of surgical
treatment of esophageal cancer 2006 to 2015 is presented. A total of 212 patients
with esophageal cancer were operated at the First Department of Surgery
University Hospital Olomouc, Czech Republic in the period between 2006 and 2015.
Adenocarcinoma was histologically described in 127 patients (59.9%), squamous
cell carcinoma in 82 patients (38.7%), and other types of carcinoma were
described in 3 cases. According to the preoperative staging of esophageal cancer,
the patients with early stage disease (T1-2N0M0) had primary surgery, while the
patients with advanced stage (T3-4N0-2M0) were indicated for neoadjuvant
chemoradiation with the surgery being performed subsequently. Transhiatal
laparoscopic esophagectomy was performed in 183 patients, and Orringer
esophagectomy in 4 patients. Thoracoscopic esophagectomy was performed in 17
patients and thoracotomy in 30 patients. Respiratory failure with the development
of ARDS syndrome accompanied by multiple-organ failure occurred in 21 patients.
Statistically significant association between mortality and ASA (p = 0.009) and
between respiratory complications and ASA (p = 0.006) was demonstrated. The
majority of patients who died were under 60 years of age (p = 0.039). Further,
significant association between 30-day mortality and tumor stage (p = 0.021),
gender (p = 0.022) and age (p = 0.018) was evident. A significant association
between tumor stage and fistula in anastomosis, (p = 0.043) was observed.
Esophagectomy is a procedure, which should be performed in specialized high
volume centers experienced in treatment of this serious malignancy and by
certified oncology surgeons with long time experience in esophageal surgery.
PMID- 29940766
TI - Long noncoding RNA LINC00313 modulates papillary thyroid cancer tumorigenesis via
sponging miR-4429.
AB - Mounting evidence indicates that long noncoding RNAs (lncRNAs) play a critical
role in tumorigenesis. LncRNA LINC00313 has been found to be up-regulated and
associated with poor prognosis in lung cancer. However, the potential role and
clinical value of LINC00313 in human papillary thyroid cancer (PTC) remain
elusive and therefore require examination. The aim of this study is to
investigate the role of LINC00313 in papillary thyroid cancer (PTC). We found its
expression was significantly up-regulated in PTC tissues and cell lines and that
this up-regulation correlated with poor prognosis. In vitro experiments indicated
that down-regulation of LINC00313 inhibited proliferation and the migratory and
colony-forming abilities of PTC cells. Moreover, silencing LINC00313 induced cell
cycle arrest and apoptosis in the PTC cells. In addition, mechanism studies
showed that LINC00313 down-regulates miR-4429 expression, and that miR-4429 over
expression can abrogate the oncogenic role of LINC00313 in PTC cells. In summary,
our data revealed that LINC00313 acts as an oncogene in PTC via sponging miR
4429, and this suggests that LINC00313 may be successfully applied as a
therapeutic target in PTC.
PMID- 29940767
TI - Knockdown of long non-coding RNA PEG10 inhibits growth, migration and invasion of
gastric carcinoma cells via up-regulating miR-3200.
AB - Gastric cancer is the main leading cause of cancer-related death worldwide. The
aberrant expression of paternally expressed gene 10 (PEG10) is involved in
development of a range of cancers. However, the potential biological function and
the underling mechanism of PEG10 in human gastric carcinoma are still unknown.
Knocking down LncRNA PEG10 might represent a promising therapeutic strategy for
the treatment of gastric cancer. The expression of PEG10, miR-3200, and AEG1 in
human gastric carcinoma NCI-N87 cells were altered by cell transfection assay.
Cell viability, migration, invasion, and apoptosis were determined by trypan blue
exclusion, Transwell assay, and flow cytometric analysis, respectively. RNA and
protein expression level of gene was analyzed by real-time PCR and Western blot.
Luciferase reporter assay was conducted to determine the target gene of miR-3200.
JNK and Wnt signal pathway protein expressions were tested by Western blot. The
up-regulation of PEG10 was found in clinical samples. PEG10 knockdown effectively
inhibited gastric carcinoma cell viability, migration, and invasion, but promoted
cell apoptosis. This tumor-suppressing effect of PEG10 knockdown might be
realized by up-regulating miR-3200 in vitro and in vivo. AEG1 was a direct target
gene of miR-3200. Moreover, miR-3200 might suppress NCI-N87 cells by negative
regulating AEG1. Up-regulating miR-3200 effectively blocked JNK and Wnt pathways
likely via down-regulating AEG1. PEG10 knockdown played a carcinostatic role via
up-regulating miR-3200 and further regulating AEG1 in gastric carcinoma cells,
during which process, JNK pathway and Wnt pathway were blocked.
PMID- 29940768
TI - Safety profile of a single pegylated asparaginase (PEG-ASP) dose in remission
induction for acute lymphoblastic leukemia (ALL).
AB - The incorporation of pegylated asparaginase (PEG-ASP) in pediatric and adult
acute lymphoblastic leukemia (ALL) protocols remains a worldwide therapeutic
approach. However the safety profile remains a challenge, and herein we report
the toxicity of an intravenous single dose of 1000 IU/m2 PEG-ASP administered in
remission induction for adult ALL patients. Thirty-two patients at median
diagnostic age of 32 years (median of 19-65) were included in this analysis. Most
patients had B-cell lymphoblastic leukemia (n=26; 78%) and 81% of cases were <55
years at study entry. 75% of patients had <30x109/l leukocyte count at diagnosis
and median follow-up was 14 months (range 0.8-69). All grade 3/4 adverse events
(AEs) after PEG-ASP administration were observed in 24 patients (75%). The most
common grade 3/4 AEs were: decreased fibrinogen (58%), increased bilirubin (31%)
and increased GGTP (27%). Clinical manifestations related to PEG-ASP were seen in
9 patients and included: abdominal pain (n=6), thrombosis (n=2), diarrhea (n=1)
and pancreatitis (n=1). The median time from PEG-ASP administration to first
toxic symptoms was 7 days (range 1-19), and there were also 4 (13%) early
induction deaths. All deaths were observed in >=50-year-old patients after a
median of 5 days following PEG-ASP (range 1-9). Three of these four patients had
massive obesity. While all expired patients had grade 4 neutropenia and
thrombocytopenia at the time of death, sepsis was not present. Administration of
PEG-ASP in induction remission for ALL patients resulted in a significant, but
mostly reversible hepatotoxicity. This PEG-ASP treatment should be administered
with caution for older, obese patients.
PMID- 29940769
TI - Up-regulation of LncRNA MEG3 inhibits cell migration and invasion and enhances
cisplatin chemosensitivity in bladder cancer cells.
AB - It has been proven that maternally expressed 3 (MEG3), a long non-coding RNA
(LncRNA), is down-regulated and inversely correlated with prognosis in various
types of cancer, including bladder cancer (BC). Nevertheless, the role of MEG3 in
BC has not been fully identified. Herein, we found that MEG3 expression was
reduced in 21 BC tumor tissue samples compared to corresponding adjacent tissues.
We then established T24 and 5637 cells with a stably integrated expression of
MEG3 by G418 resistance screening, and data revealed that the BC cells over
expressing MEG3 displayed weaker migration and invasion ability than control
cells. The expression and activity of matrix metalloproteinase (MMP)2 and MMP9
were down-regulated when MEG3 was over-expressed. Moreover, MEG3 over-expression
sensitized BC cells to the chemotherapy drug cisplatin (DDP). DDP treatment
significantly induced cell apoptosis, down-regulated bcl2 expression, and up
regulated cleaved-caspase-3 and bax expression in BC cells with MEG3 over
expression. MEG3 and p53 can also stimulate mutual expression in BC cells, thus
indicating a potential positive feedback loop of MEG3 and p53. Our combined
results suggest that over-expression of MEG3 inhibits migration and invasion and
enhances DDP chemo-sensitivity in bladder cancer cells.
PMID- 29940770
TI - Serum and urinary levels of CD222 in cancer: origin and diagnostic value.
AB - The mannose 6-phosphate/insulin-like growth factor 2 receptor (CD222, M6P/IGF2R)
is a multifunctional transmembrane type I receptor, mostly localized
intracellularly, less on the surface of all types of mammalian cells. It is known
both to transport lysosomal enzymes through their mannose 6-phosphate moieties
and to internalize extracellular ligands like insulin-like growth factor 2 or
plasminogen. CD222 is involved in regulation of cell proliferation, migration, T
cell activation, and apoptosis. Soluble CD222 has been found in higher
concentrations in sera of liver disease patients. In this study, we analysed the
level of CD222 present in body fluids, namely in serum and urine, of cancer
patients. We found significantly elevated levels of soluble CD222 in sera of
cancer patients compared to healthy controls irrespective of the type of disease.
The urine CD222 levels were increased specifically in breast cancer and multiple
myeloma. In contrast to serum, CD222 was present within CD222-positive exosomes
in urine pointing to different origins of CD222 present in various human body
fluids. Based on this work, we propose serum soluble CD222 as a general biomarker
for tumorigenesis.
PMID- 29940771
TI - The expression of clock genes cry1 and cry2 in human colorectal cancer and tumor
adjacent tissues correlates differently dependent on tumor location.
AB - Colorectal cancer (CRC) exhibits differences in its features depending on the
location of the tumor. The role of the circadian system in carcinogenesis is
accepted, and many studies report different clock gene expression in tumors
compared to healthy tissue. However, little attention is given to the changes in
clock genes in tumors arising from various locations across the colon and rectum.
The aim of our study was to investigate the expression of the clock genes cry1
and cry2 in human CRC tissue and tissue adjacent to colorectal tumors in a cohort
of 64 patients by real time PCR. Expression of cry1 in the entire patient cohort
was higher in tumors compared to adjacent tissues in the right-sided colon but
not in the left-sided colorectum. Difference in cry1 expression between tumor and
adjacent tissue in the right-sided colon was preserved in women and a trend was
observed in men. Higher expression of cry1 in the right-sided colon tumor tissue
was associated with worse survival in women and the expression of cry1 in the
left-sided colorectum was significantly higher in the adjacent tissue compared to
tumor in men but not in women. Expression of cry2 was lower in the tumor than in
adjacent tissue in both the right and left-sided colorectum. This trend was
generally preserved, but the difference reached significance level only in the
male left-sided colon, and cry2 expression in the tumor tissue significantly
correlated with location of the tumor in men with grade 2 cancer. Finally, we
detected significant correlation between tumor location and cry1 expression in
the adjacent tissue and the combined results establish that tumor influence on
adjacent tissue is dependent on tumor location. Changed clock gene expression
should therefore be considered in specific CRC patient sub-groups.
PMID- 29940772
TI - Carfilzomib combined with ex vivo-expanded patient autologous natural killer
cells for myeloma immunotherapy.
AB - Natural killer (NK) cell-based immunotherapy is promising, as NK cells are in the
first line of defense against cancer and capital of lysing tumor cells without
pre-stimulation. However, NK cells from multiple myeloma (MM) patients are always
deficient in numbers and the expression of certain activating receptors,
disabling them in cytotoxicity against the cancer. Therefore, effective
strategies to expand NK cells and increase NK cell-mediated cytotoxicity against
MM are significant. Here, NK cells were efficiently expanded from peripheral
blood mononuclear cells (PBMCs) of newly diagnosed MM patients after co-culture
with irradiated K562 cells transfected with 41BBL and membrane-bound interleukin
(IL)-15 (K562-mb15-41BBL) in the presence of 200 IU/ml human IL-2. The ex vivo
expanded NK cells were demonstrated to vigorously kill both MM cells and
autologous primary MM cells without significant lysis of patient normal cells.
Further exploration revealed a significant increase in cell surface expression of
most activating receptors of NK cells and indicated that expanded NK (exp-NK)
cell killing of MM cells was mediated by perforin/granzyme. NK cells are capital
of lysing human leukocyte antigen (HLA) I-deficient tumor cells and carfizomib, a
selective proteasome inhibitor approved for the treatment of relapsed/refractory
MM patient, down-regulates the expression of HLA class I, thus enhancing NK cell
mediated lysis in MM. Here, we found for the first time that carfizomib
dramatically augmented ex vivo exp-NK cell cytotoxicity against patient
autologous MM cells, suggesting the use of exp-NK alone or in combination with
the drug to treat MM patient.
PMID- 29940773
TI - Nicotinamide N-methyltransferase as a potential marker for cancer.
AB - Cancer is the main leading cause of death in the world, although it has been made
noteworthy advances in cancer research in the past decades. Early detection of
cancer is extremely important in improving the chances of successful therapy.
Thus, it is urgently needed to make further efforts to explore novel tumor
markers for treatment. Nicotinamide N-methyltransferase (NNMT) is a cytosolic
enzyme which catalyzes the N-methylation of nicotinamide to form 1
methylnicotinamide (1-MNA), and plays an important role in controlling the
intracellular concentration of nicotinamide. Nicotinamide, the precursor to NAD+,
is an important cofactor that associates cellular redox states with energy
metabolism. Growing evidence shows that NNMT protein levels are elevated in a
variety of human cancers, and increased NNMT expression has been linked to tumor
aggressiveness. This paper presents a review for the role of NNMT expressed in a
series of human cancers and the regulating mechanism involved, and offers its
potential value of NNMT in cancer detection and treatment.
PMID- 29940774
TI - The importance of serum osteopontin and stanniocalcin-1 in renal cell carcinoma.
AB - A total of 56 RCC patients with staging >= pT1b were enrolled in a prospective
study to assess the prognostic importance of serum levels of osteopontin (OP),
stanniocalcin-1 (SC), FGF-23, alpha Klotho and 25-OH-D at the time of diagnosis
in renal cell carcinoma (RCC) patients. The relationship between the serum level
of the analyzed parameters and recurrence-free survival (RFS), overall survival
(OS) and cancer-specific survival (CSS) was examined, and our control group
consisted of 20 patients without cancer. The levels of osteopontin, stanniocalcin
1, FGF-23 and alpha Klotho were determined by Enzyme-Linked Immunosorbent Assay
(ELISA) and 25-OH-D by chemiluminiscence immunoanalysis (CLIA). The follow-up
period median was 46 months. Renal cell carcinoma recurred in 9 patients and 20
patients died during follow-up; 12 of them from RCC. The level of osteopontin and
stanniocalcin-1 varied between the control group and RCC patients (at p=0.02 and
p=0.0003). Higher levels of stanniocalcin-1 were detected in the metastatic RCC
group than in the localized RCC group (p=0.003). Only the stanniocalcin-1 level
at the time of surgery was associated with RFS (p=0.0004). Both OS and CCS were
associated with the osteopontin, stanniocalcin-1 and FGF preoperative level.
Patients with stanniocalcin-1 level over 1,277 pg/ml and osteopontin level over
100 ng/ml had 17.8 times higher and 7.9 times higher risk of dying from RCC
progression, respectively (p<0.001 and p=0.002). High levels of osteopontin,
stanniocalcin-1 and FGF 23 at the time of surgery are important prognostic
factors related to CSS and OS. Patients with high stanniocalcin-1 level were at
risk of tumor recurrence.
PMID- 29940775
TI - Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt
pathway in laryngeal cancer cells.
AB - The early-stage diagnosis and treatment for the recurrence of larynx carcinoma
needs further investigation. Mesenchyme homeobox 2 (MEOX2) was speculated as a
novel suppressor gene in larynx carcinoma in our study, the molecular mechanism
was studied. Real-time quantitative PCR (RT-qPCR) and Western blot were used to
detect mRNA and protein levels of MEOX2 in laryngeal cancer tissues and cells
(Hep-2, TU212, AMC-NH-8 and TU686 cells), and also apoptosis and phosphoinositide
3-kinase (PI3K)/protein kinase (Akt) related factors in TU212 cells transfected
with MEOX2. Cell counting kit-8 (CCK8) assay and Annexin-V/PI staining assay were
conducted to determine cell viability and apoptosis rates respectively.46
patients with larynx carcinoma were involved in this study. The expression of
MEOX2 was lower in larynx carcinoma tissues than normal tissues, correlated with
clinical stages, differentiated degrees, and survival times. The expression of
MEOX2 was the lowest among those laryngeal cancer cells, and was chosen to be
transfected with MEOX2 in the following study. Over-expression of MEOX2 inhibited
cell viability and promoted apoptosis of TU212 cells, via increasing the
expression levels of Caspase-3, and decreasing levels of C-Myc, XIAP, PI3K
p110alpha, PI3K p110beta, PI3K class III and p-Akt. In summary, the expression
levels of MEOX2 were inhibited in larynx carcinoma than normal tissues,
correlated with the progression of the cancer. Over-expression of MEOX2 in
laryngeal cancer cells inhibited cell viability and promoted apoptosis, via
regulating apoptosis and PI3K/Akt pathway related factors. It would provide
evidence for MEOX2 to be used as a therapeutical gene in larynx carcinoma.
PMID- 29940776
TI - Long non-coding RNA PICART1 suppresses proliferation and promotes apoptosis in
lung cancer cells by inhibiting JAK2/STAT3 signaling.
AB - Lung cancer remains the most common cause of tumor-related death worldwide.
Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in
the development of various cancers, including lung cancer. This study aimed to
investigate the effect and the molecular basis of lncRNA PICART1 on lung cancer.
We first assessed the PICART1 expression in lung cancer in vitro and vivo by qRT
PCR. Then the expression of PICART1 in SPC-A-1 and NCI-H1975 cell lines was
inhibited and overexpressed by transient transfections. Thereafter, cell
viability, cell cycle, migration and apoptosis were respectively measured by MTT,
Transwell and flow cytometry assay. Furthermore, qRT-PCR and western blot
analysis were mainly performed to assess the expression levels of apoptosis- and
migration-related proteins and JAK2/STAT3 pathway proteins. Tumor formation was
measured by xenograft tumor model assay in vivo. PICART1 expression was down
regulated in human lung cancer tissues and cell lines. Knockdown of PICART1
increased cell viability of lung cancer cell lines. However, PICART1
overexpression inhibited cell cycle progression and promoted apoptosis in SPC-A-1
and NCI-H1975 cell lines. PICART1 overexpression also inhibited migration, as
evidenced by up-regulation of E-cadherin, and down-regulation of Twist1, MMP2 and
MMP9. Furthermore, we found PICART1 inhibition may regulate cell apoptosis and
migration through activating JAK2/STAT3 pathway. In vivo experiments revealed
that PICART1 knockdown significantly promoted tumor formation. This study
demonstrates that PICART1 overexpression represents an anti-growth and anti
metastasis role in lung cancer cells. Additionally, PICART1 acts as a tumor
suppressor may be via regulation of JAK2/STAT3 pathway.
PMID- 29940777
TI - The study of bacteria in biopsies from Slovak colorectal adenoma and carcinoma
patients.
AB - The development of colorectal cancer is affected by many factors, especially the
intestinal microbiota. However, precise knowledge of bacterial communities
associated with the mucosa in various parts of the colon is limited. Herein, we
applied the gentamicin protection assay and detected the presence of
intracellular bacteria in colorectal biopsies from Slovak patients with
colorectal adenoma and carcinoma, and we compared this with healthy controls. The
ENTEROtest 24 and MALDI-TOF mass spectrometry identified the cultivated bacteria
and results revealed the presence of intracellularly localized Escherichia coli,
Proteus mirabilis and Proteus vulgaris in patients with colorectal adenomas and
carcinomas. In addition to these species, Klebsiella pneumoniae, Pseudomonas
aeruginosa, Enterococcus faecalis and Bacillus cereus were identified in
colorectal biopsies, but these were extracellular. The marked increase in
relative abundance of intracellular E. coli in patients with colorectal adenomas
and carcinomas was statistically significant compared to controls, and our
preliminary data supports E. coli's role as a pro-oncogenic pathogen.
PMID- 29940778
TI - miR-144 functions as an oncomiR in KYSE-410 human esophageal carcinoma cell line
in vitro and targets PURA.
AB - Esophageal cancer (EC) is a highly complex disease with high incidence and
mortality rates. Recent studies have shown that miRNAs play critical roles in
diverse biological processes including oncogenesis, and we previously reported
significantly increased expression of tissue and circulating miR-144 in EC. This
study evaluates the functional significance of miR-144 in esophageal squamous
cell carcinoma. Herein, we analysed the role of miR-144 in ESCC by silencing it
in KYSE-410 cells, and followed this with cell cycle analysis and the following
assays; MTT, annexin, colony formation, scratch and matrigel invasion assay. The
miR-144 knockdown significantly suppressed ESCC cell proliferation at 72 hours
post transfection (p=0.029). Silencing of miR-144 significantly decreased the
migration, invasion and colony formation potential of KYSE-410 cells compared to
cells treated with negative control (NC). Potential targets of miR-144 were
predicted by the in silico approach followed by in vitro validation in real time
PCR and luciferase reporter assay. The PURA and Spred1 in silico predicted miR
144 targets were validated by qRT-PCR and luciferase reporter assay. Over
expression of miR-144 significantly decreased PURA mRNA expression by 58.85% at
24 hours post transfection (p=0.009). Further validation by dual-luciferase
reporter assay confirmed it is a direct targets of miR-144. Our overall study
suggests the oncogenic role of miR-144 in EC by promoting proliferation and
migration of ESCC cells. To the best of our knowledge, this is the first report
showing PURA as a direct miR-144 downstream target and suggests its potential as
a novel therapeutic target for this disease.
PMID- 29940779
TI - Cardiovascular disease among United States military veterans: Evidence of a
waning healthy soldier effect using the National Health Interview Survey.
AB - Objectives Cardiovascular disease is the most common chronic health condition
affecting Americans. One important group of Americans that health researchers
have noted as key to understanding general population health and wellbeing are
veterans of the US military. The healthy soldier effect has been used to explain
the health benefits of military service during and for a period of time after
service. The purpose of this study is to examine the prevalence of cardiovascular
disease in a national sample of veterans and non-veterans with specific attention
paid to reported cardiovascular disease across ages. Methods A total of 150,067
veteran and non-veteran respondents from the National Health Interview Survey
were examined for the likelihood of reporting the type and number of
cardiovascular conditions. Results Veterans report higher rates of certain
cardiovascular disease conditions and report a higher number of cardiovascular
disease conditions compared to non-veterans. Veterans also reported higher
numbers of cardiovascular disease conditions at younger ages (ages 25-65)
compared to non-veteran counterparts. At older ages (ages 66 to 85+), non
veterans reported higher numbers of cardiovascular disease conditions compared to
veterans. Discussion Our findings are consistent with research that indicates a
waning healthy soldier effect for young veterans.
PMID- 29940780
TI - A Quarter of a Century Later: What is Dofetilide's Clinical Role Today?
AB - Dofetilide is a class III antiarrhythmic agent approved by the Food and Drug
Administration for the conversion of atrial fibrillation and atrial flutter and
maintenance of sinus rhythm in symptomatic patients with persistent arrhythmia.
Drug trials showed neutral mortality in post-myocardial infarction patients and
those with heart failure. This is a review of postmarket data, including real
world efficacy and safety in a variety of populations. Dofetilide has been used
off-label with success in patients with paroxysmal atrial fibrillation and atrial
flutter, as well as atrial tachycardia and ventricular tachycardia. The real
world acute conversion rate of atrial fibrillation and atrial flutter is higher
than that reported in clinical trials. Dofetilide has an acceptable safety
profile when initiated (or reloaded) under hospital monitoring and dosed
according to creatinine clearance. Dofetilide is well tolerated and a good choice
for patients with acceptable renal function and a normal QT interval, especially
if atrioventricular nodal blockade needs to be avoided.
PMID- 29940781
TI - Current understanding of photophobia, visual networks and headaches.
AB - Objective To review clinical and pre-clinical evidence supporting the role of
visual pathways, from the eye to the cortex, in the development of photophobia in
headache disorders. Background Photophobia is a poorly understood light-induced
phenomenon that emerges in a variety of neurological and ophthalmological
conditions. Over the years, multiple mechanisms have been proposed to explain its
causes; however, scarce research and lack of systematic assessment of photophobia
in patients has made the search for answers quite challenging. In the field of
headaches, significant progress has been made recently on how specific visual
networks contribute to photophobia features such as light-induced intensification
of headache, increased perception of brightness and visual discomfort, which are
frequently experienced by migraineurs. Such progress improved our understanding
of the phenomenon and points to abnormal processing of light by both cone/rod
mediated image-forming and melanopsin-mediated non-image-forming visual pathways,
and the consequential transfer of photic signals to multiple brain regions
involved in sensory, autonomic and emotional regulation. Conclusion Photophobia
phenotype is diverse, and the relative contribution of visual, trigeminal and
autonomic systems may depend on the disease it emerges from. In migraine,
photophobia could result from photic activation of retina-driven pathways
involved in the regulation of homeostasis, making its association with headache
more complex than previously thought.
PMID- 29940782
TI - Predicting Clinical Gains and Side Effects of Stimulant Medication in Pediatric
Attention-Deficit/Hyperactivity Disorder by Combining Measures From qEEG and ERPs
in a Cued GO/NOGO Task.
AB - OBJECTIVES: The study aim was to develop 2 scales: predicting clinical gains and
risk of acute side effects of stimulant medication in pediatric attention
deficit/hyperactivity disorder (ADHD), combining measures from EEG spectra, event
related potentials (ERPs), and a cued visual GO/NOGO task. METHODS: Based on 4
week systematic medication trials, 87 ADHD patients aged 8 to 17 years were
classified as responders (REs, n = 62) or non-REs (n = 25), and belonging to the
side effects (SEs, n = 42) or no-SEs (n = 45) groups. Before starting the trial,
a 19-channel EEG was registered twice: Test 1 (T1) without medication and T2 on a
single dose of stimulant medication a few days before the trial. EEG was
registered T1 and T2: 3 minutes eyes-closed, 3 minutes eyes-open, and 20 minutes
cued GO/NOGO. EEG spectra, ERPs, omissions, commissions, reaction time (RT), and
RT variability were computed. Groups were compared at T1 and T2 on quantitative
EEG (qEEG), ERPs and behavioral parameters; effect sizes ( d) were estimated.
Variables with d > 0.5 were converted to quartiles, multiplied by corresponding
d, and summed to obtain 2 global scales. RESULTS: Six variables differed
significantly between REs and non-REs (T1: theta/alpha ratio, P3NOGO amplitude.
Differences T2-T1: Omissions, RT variability, P3NOGO, contingent negative
variation [CNV]). The global scale d was 1.86. Accuracy (receiver operating
characteristic) was 0.92. SEs and no-SEs differed significantly on 4 variables.
(T1: RT, T2: novelty component and alpha peak frequency, and RT changes. Global
scale d = 1.08 and accuracy = 0.78. CONCLUSION: Gains and side effects of
stimulants in pediatric ADHD can be predicted with high accuracy by combining EEG
spectra, ERPs, and behavior from baseline and single-dose tests.
ClinicalTrials.gov identifier: NCT02695355.
PMID- 29940783
TI - Neutrophil to Lymphocyte Ratio as a Predictor of Restenosis After Angioplasty and
Stenting for Asymptomatic Carotid Stenosis.
AB - The inflammatory response plays a vital role in the development of in-stent
restenosis (ISR) after carotid angioplasty and stenting (CAS). The neutrophil to
lymphocyte ratio (NLR) has been suggested as a sensitive inflammatory marker. We
explored the association between NLR and ISR in CAS patients. A total of 427
patients who underwent CAS were enrolled. Neutrophil to lymphocyte ratio was
measured before the procedure. Clinical examination and radiographic evaluation
were performed at 6 months and annually after the procedure. In-stent restenosis
was defined as >=50% stenosis in the treated lesion. Cox regression was used to
identify predictors of ISR after CAS. Of the 459 arteries (in 427 patients) with
CAS, 72 (15.7%) were identified with ISR during a mean follow-up of 14.6 (19.1)
months (range, 0.7-120.7 months). Increased NLR (>=2.13) was significantly
related to ISR in patients with asymptomatic stenosis ( P = .001). However,
significance was not observed in symptomatic stenosis. On multivariate analysis,
baseline NLR >= 2.13 (hazard ratio [HR], 2.74; 95% confidence interval [CI], 1.46
5.14), smoking (HR, 1.99; 95% CI, 1.11-3.58), residual stenosis (HR, 1.12; 95%
CI, 1.09-1.15), and baseline glucose level (HR, 1.01; 95% CI, 1.01-1.02) were
associated with ISR. Elevated NLR may be a predictor of ISR after CAS for
asymptomatic stenosis.
PMID- 29940784
TI - The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition on Sterol
Absorption Markers in a Cohort of Real-World Patients.
AB - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed in
multiple tissues, including the small intestine. The effect of PCSK9 inhibition
on cholesterol absorption is not known. OBJECTIVES: Measure serum cholesterol
absorption markers before and after initiation of PCSK9 inhibitors. METHODS:
Single-center retrospective cohort of patients administered evolocumab and
alirocumab between July 2015 and January 2017. Paired t tests were used to
compare mean serum cholesterol marker concentrations, and ratios to total
cholesterol, before and after PCSK9 inhibitor initiation. Analyses were repeated
for those taking and not taking statins and taking or not taking ezetimibe at
both initiation and follow-up, for each PCSK9 inhibitor, and based on follow-up
time (<60, 60-120, and >120 days). RESULTS: There were 62 possible participants,
34 were excluded for lack of data or unknown PCSK9 inhibitor initiation date.
Average follow-up was 92.5 days. Mean campesterol (before 3.14 MUg/mL, 95% CI:
2.79-4.38 MUg/mL; after 2.09 MUg/mL, 95% CI: 1.87-2.31 MUg/mL; P < .0001),
sitosterol (before 2.46 MUg/mL, 95% CI: 2.23-2.70 MUg/mL; after 1.62 MUg/mL, 95%
CI: 1.48-1.75 MUg/mL; P < .0001), and cholestanol (before 3.25 MUg/mL, 95% CI:
3.04-3.47 MUg/mL; after 2.08 MUg/mL, 95% CI: 1.96-2.21 MUg/mL; P < .0001) all
significantly decreased at follow-up. There was no significant change in
absorption marker to total cholesterol ratios. Findings were not influenced by
statin or ezetimibe use or nonuse, which PCSK9 inhibitor was prescribed, or time
to follow-up. CONCLUSION: Proprotein convertase subtilisin/kexin type 9
inhibition was associated with decreased cholesterol absorption markers.
PMID- 29940785
TI - Inhibiting autophagy reduces retinal degeneration caused by protein misfolding.
AB - Mutations in the genes necessary for the structure and function of vertebrate
photoreceptor cells are associated with multiple forms of inherited retinal
degeneration. Mutations in the gene encoding RHO (rhodopsin) are a common cause
of autosomal dominant retinitis pigmentosa (adRP), with the Pro23His variant of
RHO resulting in a misfolded protein that activates endoplasmic reticulum stress
and the unfolded protein response. Stimulating macroautophagy/autophagy has been
proposed as a strategy for clearing misfolded RHO and reducing photoreceptor
death. We found that retinas from mice heterozygous for the gene encoding the
RHOP23H variant (hereafter called P23H) exhibited elevated levels of autophagy
flux, and that pharmacological stimulation of autophagy accelerated retinal
degeneration. In contrast, reducing autophagy flux pharmacologically or by rod
specific deletion of the autophagy-activating gene Atg5, improved photoreceptor
structure and function. Furthermore, proteasome levels and activity were reduced
in the P23H retina, and increased when Atg5 was deleted. Our findings suggest
that autophagy contributes to photoreceptor cell death in P23H mice, and that
decreasing autophagy shifts the degradation of misfolded RHO protein to the
proteasome and is protective. These observations suggest that modulating the flux
of misfolded proteins from autophagy to the proteasome may represent an important
therapeutic strategy for reducing proteotoxicity in adRP and other diseases
caused by protein folding defects.
PMID- 29940787
TI - Revisiting LAMP1 as a marker for degradative autophagy-lysosomal organelles in
the nervous system.
AB - : Lysosomes serve as the degradation hubs for macroautophagic/autophagic and
endocytic components, thus maintaining cellular homeostasis essential for
neuronal survival and function. LAMP1 (lysosomal associated membrane protein 1)
and LAMP2 are distributed among autophagic and endolysosomal organelles. Despite
widespread distribution, LAMP1 is routinely used as a lysosome marker and LAMP1
positive organelles are often referred to as lysosomal compartments. By applying
immuno-electron microscopy (iTEM) and confocal imaging combined with Airyscan
microscopy, we expand on the limited literature to provide a comprehensive and
quantitative analysis of LAMP1 distribution in various autophagic and
endolysosomal organelles in neurons. Our study demonstrates that a significant
portion of LAMP1-labeled organelles lack major lysosomal hydrolases. BSA-gold
pulse-chase assay further shows heterogeneous degradative capacities of LAMP1
labled organelles. In addition, LAMP1 intensity is not a sensitive readout to
assess lysosomal deficits in familial amyotrophic lateral sclerosis-linked motor
neurons in vivo. Our study thus calls for caution when interpreting LAMP1-labeled
organelles in the nervous system where LAMP1 intensity, trafficking, and
distribution do not necessarily represent degradative lysosomes or autolysosomes
under physiological and pathological conditions. ABBREVIATIONS: ALS: amyotrophic
lateral sclerosis; BSA: bovine serum albumin; DRG: dorsal root ganglion; IGF2R/CI
M6PR: insulin like growth factor 2 receptor; iTEM: immuno-transmission electron
microscopy; LAMP1/2: lysosomal associated membrane protein 1/2; P80: postnatal
day 80; sMNs: spinal motor neurons.
PMID- 29940789
TI - Identification of epigenetic modulators in human breast cancer by integrated
analysis of DNA methylation and RNA-Seq data.
AB - Human tumors undergo massive changes in DNA methylation. Recent studies showed
that site-specific methylation of CpG sites is determined by the DNA sequence
context surrounding the CpG site, which alludes to a possible mechanism for site
specific aberrant DNA methylation in cancer through DNA-binding proteins. In this
paper, DNA methylation data and RNA-Seq data of breast tumors and normal tissues
in the database of The Cancer Genome Atlas (TCGA) were integrated with
information of DNA motifs in seven databases to find DNA-binding proteins and
their binding motifs that were involved in aberrant DNA methylation in breast
cancer. A total of 42,850 differentially methylated regions (DMRs) that include
77,298 CpG sites were detected in breast cancer. One hundred eight DNA motifs
were found to be enriched in DMRs, and 109 genes encoding proteins binding to
these motifs were determined. Based on these motifs and genes, 63 methylation
modulator genes were identified to regulate differentially methylated CpG sites
in breast cancer. A network of these 63 modulator genes and 645 transcription
factors was constructed, and 20 network modules were determined. A number of
pathways and gene sets related to breast cancer were found to be enriched in
these network modules. The 63 methylation modulator genes identified may play an
important role in aberrant methylation of CpG sites in breast cancer. They may
help to understand site-specific dysregulation of DNA methylation and provide
epigenetic markers for breast cancer.
PMID- 29940788
TI - Developmental surface dysgraphia without surface dyslexia.
AB - The case is reported of an individual (N.K.) with a developmental spelling
impairment (dysgraphia) who has no apparent problems in reading. His performance
therefore provides further evidence of a classical dissociation between impaired
spelling and preserved reading in individuals with developmental literacy
problems. The dissociation is observed when N.K. is asked to read and spell in
either his first (Greek) or his second language (English). An investigation of
his spelling performance revealed that his impairment was more selective than
that of P.J.T. Although his spelling of regular words and nonwords was normal,
N.K. had a problem in spelling words with atypical sound-letter associations
despite having no problems in reading aloud or understanding the meaning of words
of this kind. It is argued that N.K.'s pattern of performance can be best
explained in terms of normal development of an orthographic system that allows
access to the meaning and pronunciation of written words during reading. In terms
of a dual-route model of spelling, his poor spelling appears to be the result of
a developmental impairment that impedes access to the orthographic system from
phonology and semantics. In terms of the triangle model, his poor spelling
appears to be the result of a developmental impairment that affects activation of
orthography from semantics.
PMID- 29940786
TI - Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion.
AB - Macroautophagy/autophagy is a conserved transport pathway where targeted
structures are sequestered by phagophores, which mature into autophagosomes, and
then delivered into lysosomes for degradation. Autophagy is involved in the
pathophysiology of numerous diseases and its modulation is beneficial for the
outcome of numerous specific diseases. Several lysosomal inhibitors such as
bafilomycin A1 (BafA1), protease inhibitors and chloroquine (CQ), have been used
interchangeably to block autophagy in in vitro experiments assuming that they all
primarily block lysosomal degradation. Among them, only CQ and its derivate
hydroxychloroquine (HCQ) are FDA-approved drugs and are thus currently the
principal compounds used in clinical trials aimed to treat tumors through
autophagy inhibition. However, the precise mechanism of how CQ blocks autophagy
remains to be firmly demonstrated. In this study, we focus on how CQ inhibits
autophagy and directly compare its effects to those of BafA1. We show that CQ
mainly inhibits autophagy by impairing autophagosome fusion with lysosomes rather
than by affecting the acidity and/or degradative activity of this organelle.
Furthermore, CQ induces an autophagy-independent severe disorganization of the
Golgi and endo-lysosomal systems, which might contribute to the fusion
impairment. Strikingly, HCQ-treated mice also show a Golgi disorganization in
kidney and intestinal tissues. Altogether, our data reveal that CQ and HCQ are
not bona fide surrogates for other types of late stage lysosomal inhibitors for
in vivo experiments. Moreover, the multiple cellular alterations caused by CQ and
HCQ call for caution when interpreting results obtained by blocking autophagy
with this drug.
PMID- 29940790
TI - A Multimodal Skin Cancer Prevention Program for Heart Transplant Patients.
AB - BACKGROUND: Immunosuppressant medications are essential for long-term survival
following transplantation but increase the risk of developing skin cancer.
Prevention and early detection of skin cancer requires screening and sun
protection behaviors that can be achieved with patient education. PROBLEM
STATEMENT: Our method for educating post heart transplant patients regarding skin
cancer was inconsistent and was not effective. The aim of this project was to
develop and integrate a multimodal skin cancer education program to increase
knowledge and protective behaviors for heart transplant recipients. METHODS:
Twenty-five post heart transplant patients who were scheduled to be seen for
routine posttransplant care at a single-center transplant center between October
26, 2016, and November 15, 2016, took part in a multimodal skin cancer education
program. RESULTS: There was a significant increase in knowledge between pretest
and posttest 1 ( P <.01) and pretest and posttest 2 ( P <.01). A significant
increase in sun protective behavior was noted. The project noted that knowledge
and behavior was retained, knowledge score posttest 1 to posttest 2 ( P = .085),
all had seen a dermatologist or had an appointment scheduled, and self skin exam
retention was noted between posttest 1 and posttest 2 ( P = .25). Process
Addressed: The feasibility of and findings from this intervention have led the
clinic team to implement this protocol as part of the standard care for all
patients. CONCLUSIONS: These data suggests that a multimodal intensive skin
cancer education program may be effective at increasing knowledge and protective
behavior with heart transplant recipients.
PMID- 29940791
TI - Phagophores evolve from recycling endosomes.
AB - The membrane origins of autophagosomes have been a key unresolved question in the
field. The earliest morphologically recognizable structure in the
macroautophagy/autophagy itinerary is the double-membraned cup-shaped phagophore.
Newly formed phosphatidylinositol 3-phosphate (PtdIns3P) on the membranes
destined to become phagophores recruits WIPI2, which, in turn, binds ATG16L1 to
define the sites of autophagosome formation. Here we review our recent study
showing that membrane recruitment of WIPI2 requires coincident detection of
PtdIns3P and RAB11A, a protein that marks recycling endosomes. We found that
multiple core autophagy proteins are more tightly associated with the recycling
endosome compartment than with endoplasmic reticulum (ER)-mitochondrial contact
sites. Furthermore, biochemical isolation of the recycling endosomes confirmed
that they recruit autophagy proteins. Finally, fixed and live-cell imaging data
revealed that recycling endosomes engulf autophagic substrates. Indeed, the
sequestration of mitochondria after mitophagy stimulation depends on early
autophagy regulators. These data suggest that autophagosomes evolve from the
RAB11A compartment.
PMID- 29940792
TI - Peritumoral monocytes induce cancer cell autophagy to facilitate the progression
of human hepatocellular carcinoma.
AB - Macroautophagy/autophagy is an important catabolic process mediating cellular
homeostasis and plays critical roles in cancer development. Whereas autophagy has
been widely studied in various pathological models, little is known about the
distribution, clinical significance and regulatory mechanism of this process in
human hepatocellular carcinoma (HCC). In the present study, we found that tumor
tissues exhibited significantly increased levels of autophagy compared with non
tumor tissues, and cancer cells with higher levels of autophagy were
predominantly enriched in the invading edge regions of human HCC. Increased
MAP1LC3B/LC3B expression in the invading edge regions was significantly
correlated with a higher density of closely located monocytes, and TNF and IL1B
derived from tumor-activated monocytes synergistically induced cancer cell
autophagy in the invading edge regions of HCC. Monocyte-elicited autophagy
induced the epithelial-mesenchymal transition (EMT) of cancer cells and promoted
tumor metastasis by activating the NFKB-SNAI1 signaling pathway. Moreover, the
increase of LC3B+ cancer cells in the invading edge areas was associated with
high mortality and reduced survival of patients with HCC. These findings
indicated that cancer cell autophagy is regulated by a collaborative interaction
between tumor and immune cell components in distinct HCC microenvironments, thus
allowing the inflammatory monocytes to be rerouted in a tumor-promoting
direction.
PMID- 29940793
TI - Early butyrate induced acetylation of histone H4 is proteoform specific and
linked to methylation state.
AB - Histone posttranslational modifications (PTMs) help regulate DNA templated
processes; however, relatively little work has unbiasedly explored the single
molecule combinations of histone PTMs, their dynamics on short timescales, or how
these preexisting histone PTMs modulate further histone modifying enzyme
activity. We use quantitative top down proteomics to unbiasedly measure histone
H4 proteoforms (single-molecule combinations of PTMs) upon butyrate treatment.
Our results show that histone proteoforms change in cells within 10 minutes of
application of sodium butyrate. Cells recover from treatment within 30 minutes
after removal of butyrate. Surprisingly, K20me2 containing proteoforms are the
near-exclusive substrate of histone acetyltransferases upon butyrate treatment.
Single-molecule hierarchies of progressive PTMs mostly dictate the addition and
removal of histone PTMs (K16ac > K12ac >= K8ac > K5ac, and the reverse on
recovery). This reveals the underlying single-molecule mechanism that explains
the previously reported but indistinct and unexplained patterns of H4
acetylation. Thus, preexisting histone PTMs strongly modulate histone modifying
enzyme activity and this suggests that proteoform constrained reaction pathways
are crucial mechanisms that enable the long-term stability of the cellular
epigenetic state.
PMID- 29940795
TI - Diagnostic approach to neuropsychiatric lupus erythematosus: what should we do?
AB - Neuropsychiatric systemic lupus erythematosus is a diagnostic challenge due to
the multifarious neurological and psychiatric manifestations that define it but,
when suspected, diagnostic imaging can give a fundamental help. The advancements
and variety of neuroimaging techniques allow us to perform more and more accurate
evaluations of structure, perfusion, and metabolism of the brain and to detect
cerebral and spinal lesions. Moreover, vascular districts of the neck and the
brain, as well as the electrical brain and peripheral muscle activity may be
accurately investigated, thus giving us a wide panoramic view. Although magnetic
resonance is recognized as a fundamental neuroimaging technique to reach a
correct diagnosis, the juxtaposition of other diagnostic techniques has improved
the possibility to make diagnoses but has also increased the confusion about
deciding which of them to use and when. Our aim was to combine the number of
available techniques with the need to simplify the diagnostic path. Therefore,
through the construction of an algorithm from an evidence based approach, we
believe we are providing some added improvements to facilitate and expedite the
diagnosis of NPSLE.
PMID- 29940794
TI - Silica nanoparticles induce autophagosome accumulation via activation of the
EIF2AK3 and ATF6 UPR pathways in hepatocytes.
AB - Autophagy dysfunction is a potential toxic effect of nanoparticles. Previous
studies have indicated that silica nanoparticles (SiNPs) induce
macroautophagy/autophagy dysfunction, while the precise mechanisms remain
uncertain. Hence, the present study investigated the molecular mechanisms by
which SiNPs enhanced autophagosome synthesis, which then contributed to autophagy
dysfunction. First, the effects of SiNPs on autophagy and autophagic flux were
verified using transmission electron microscopy, laser scanning confocal
microscopy, and western blot assays. Then, the activation of endoplasmic
reticular (ER) stress was validated to be through the EIF2AK3 and ATF6 UPR
pathways but not the ERN1-XBP1 pathway, along with the upregulation of downstream
ATF4 and DDIT3. Thereafter, the ER stress inhibitor 4-phenylbutyrate (4-PBA) was
used to verify that SiNP-induced autophagy could be influenced by ER stress.
Furthermore, specialized lentiviral shRNA were employed to determine that
autophagy was induced via specific activation of the EIF2AK3 and ATF6 UPR
pathways. Finally, the 2 autophagic genes LC3B and ATG12 were found to be
transcriptionally upregulated by downstream ATF4 and DDIT3 in ER stress, which
contributed to the SiNP-enhanced autophagosome synthesis. Taken together, these
data suggest that SiNPs induced autophagosome accumulation via the activation of
the EIF2AK3 and ATF6 UPR pathways in hepatocytes, which offers a new insight into
detailed molecular mechanisms underlying SiNP-induced autophagy dysfunction, and
specifically how UPR pathways regulate key autophagic genes. This work provides
novel evidence for the study of toxic effects and risk assessment of SiNPs.
PMID- 29940796
TI - Sources of variability in hospital administrative data: Clinical coding of
postoperative ileus.
AB - BACKGROUND: Multiple studies have questioned the validity of clinical codes in
hospital administrative data. We examined variability in reporting a
postoperative ileus (POI). OBJECTIVE: We aimed to analyse sources of coding
variations to understand how clinical coding professionals arrive at POI coding
decisions and to verify existing knowledge that current clinical coding practices
lack standardised applications of regulatory guidelines. METHOD: Two medical
records (cases 1 and 2) were provided to 15 clinical coders employed by a midsize
nonprofit hospital in the northwest region of the United States. After coding
these cases, the study participants completed a survey, reported on the
application of guidelines, and participated in a focus group led by a health
information management regulatory compliance expert. RESULTS: Only 5 of the 15
clinical coders correctly indicated no POI complication in case 1 where the
physician documentation did not establish a link between the POI as a
complication of care and the surgery. In contrast, 13 of the 15 study
participants correctly coded case 2, which included clear physician documentation
and contained the clinical parameters for the coding of the POI as a complication
of care. Clinical coder education, credentials, certifications, and experience
did not relate to the coding performance. The clinical coders inconsistently
prioritised coding rules and valued experience more than education. CONCLUSION
AND IMPLICATIONS: The application of International Classification of Diseases,
Ninth Revision, Clinical Modification; coding conventions; Centers for Medicare
and Medicaid Services coding guidelines; and American Hospital Association coding
clinic advice was subject to the clinical coders' interpretation; they perceived
them as conflicting guidance. Their reliance on subjective experience in dealing
with this conflicting guidance may limit the accuracy of reporting outcomes of
clinical performance.
PMID- 29940797
TI - Tele-delivered mindfulness-based cognitive therapy in chronic obstructive
pulmonary disease: A mixed-methods feasibility study.
AB - Introduction Mindfulness-based cognitive therapy has been shown to reduce
psychological distress in chronic obstructive pulmonary disease, but uptake and
attendance rates of hospital-based, face-to-face mindfulness-based cognitive
therapy are low. The present mixed-methods study evaluates the clinical
feasibility of home-based, tele-delivered mindfulness-based cognitive therapy in
chronic obstructive pulmonary disease. Methods Eight patients with chronic
obstructive pulmonary disease (mean age: 72.6 years; 50% female) received a
standardised eight-week mindfulness-based cognitive therapy programme delivered
via home-based video-conferences in groups of four. Feasibility in relation to
(a) clinical change, (b) attendance and (c) instructor-patient working alliance
were evaluated with questionnaires and semi-structured interviews. Results
Statistically non-significant reductions in psychological distress (Cohen's d =
0.504; p = 0.399) and physical health status impairment ( d = 0.743; p = 0.156)
were observed from pre- to post-intervention. Participant narratives about
clinical outcomes focused on changes in how to relate to unpleasant sensations,
i.e. through attentional flexibility, taking a pause and acceptance. The average
attendance rate was 7.5 (standard deviation = 0.8) out of eight sessions and no
participants dropped out. The tele-based format appeared to accommodate
participants' planning difficulties and promoted their ability and wish to
participate. Although participant narratives suggested the tele-based format to
be a barrier to developing a trusting and safe therapeutic environment, working
alliance questionnaire scores were comparable to those found for face-to-face
mindfulness-based cognitive therapy. Discussion The preliminary results indicate
that tele-delivered mindfulness-based cognitive therapy is a clinically feasible
intervention in chronic obstructive pulmonary disease. Future large-scale,
randomised controlled trials testing its efficacy on the outcomes of
psychological distress and physical health status should include analyses of
potential mediators and moderators of the effect as well as and careful
monitoring of attendance and adverse events.
PMID- 29940798
TI - Aging Alters Circadian Rhythms in the Mouse Eye.
AB - The eye contains a circadian system that acts independently from the master
circadian clock located in the brain. This circadian system regulates important
physiological functions within the eye. Emerging experimental evidence also
indicates that disruption of the ocular circadian clock, or its outputs,
negatively affects the overall health of the eye. Although previous studies have
investigated the effect of aging on the regulation of circadian rhythms, no study
has investigated the effects of aging on the circadian rhythm in the ocular
system. The aim of the present study was to investigate how aging affects the
circadian rhythm of PER2::LUC bioluminescence in the retina, retinal pigment
epithelium (RPE), and cornea. Our data suggest that among the 3 different ocular
tissues investigated, the retina appears to be the most affected by aging whereas
the RPE and cornea are less affected by aging. Our data, along with studies of
other organs and tissues, suggest that reduction in the amplitude of rhythms is
probably the most severe effect of aging on the circadian clock.
PMID- 29940799
TI - IRE1B degrades RNAs encoding proteins that interfere with the induction of
autophagy by ER stress in Arabidopsis thaliana.
AB - : Macroautophagy/autophagy is a conserved process in eukaryotes that contributes
to cell survival in response to stress. Previously, we found that endoplasmic
reticulum (ER) stress induces autophagy in plants via a pathway dependent upon
AT5G24360/IRE1B (INOSITOL REQUIRING 1-1), an ER membrane-anchored factor involved
in the splicing of AT1G42990/BZIP60 (basic leucine zipper protein 60) mRNA. IRE1B
is a dual protein kinase and ribonuclease, and here we determined the involvement
of the protein kinase catalytic domain, nucleotide binding and RNase domains of
IRE1B in activating autophagy. We found that the nucleotide binding and RNase
activity of IRE1B, but not its protein kinase activity or splicing target BZIP60,
are required for ER stress-mediated autophagy. Upon ER stress, the RNase activity
of IRE1B engages in regulated IRE1-dependent decay of messenger RNA (RIDD), in
which mRNAs of secreted proteins are degraded by IRE1 upon ER stress. Twelve
genes most highly targeted by RIDD were tested for their role in inhibiting ER
stress-induced autophagy, and 3 of their encoded proteins, AT1G66270/BGLU21 (beta
glucosidase 21), AT2G16005/ROSY1/ML (MD2-related lipid recognition protein) and
AT5G01870/PR-14 (pathogenesis-related protein 14), were found to inhibit
autophagy upon overexpression. From these findings, IRE1B is posited to be a
'licensing factor' linking ER stress to autophagy by degrading the RNA
transcripts of factors that interfere with the induction of autophagy.
ABBREVIATIONS: ACT2: actin 2; ATG: autophagy-related; BGLU21: beta-glucosidase
21; BIP3: binding protein 3; BZIP: basic leucine zipper; DAPI: 4', 6-diamidino-2
phenylindole; DTT: dithiothreitol; ER: endoplasmic reticulum; ERN1: endoplasmic
reticulum to nucleus signaling 1; IRE1: inositol requiring 1; GFP: green
fluorescent protein; MAP3K5/ASK1: mitogen-activated protein kinase kinase kinase
5; MAPK8/JNK1: mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1; MDC:
monodansylcadaverine; PR-14: pathogenesis-related protein 14; RIDD: Regulated
IRE1-Dependent Decay of Messenger RNA; ROSY1/ML: interactor of synaptotagmin1/MD2
related lipid recognition protein; Tm: tunicamycin; UPR: unfolded protein
response; WT: wild-type.
PMID- 29940801
TI - Musicians' Natural Frequencies of Performance Display Optimal Temporal Stability.
AB - Many human action sequences, such as speaking and performing music, are
inherently rhythmic: Sequence events are produced at quasi-regular temporal
intervals. A wide range of interindividual variation has been noted in
spontaneous production rates of these rhythmic action sequences. Dynamical
theories of motor coordination suggest that individuals spontaneously produce
rhythmic sequences at a natural frequency characterized by minimal energy
expenditure and maximal temporal stability, relative to other frequencies. We
tested this hypothesis by comparing the temporal variability with which musicians
performed rhythmic melodies at their natural spontaneous rate with variability in
their performances at faster and slower rates. Musicians' temporal variability
was lowest during performances at their spontaneous rate; in addition,
performers' tempo drift during trials at other rates showed bias toward their
spontaneous rate. This study provides the first direct evidence that spontaneous
rates of motor coordination represent optimally stable natural frequencies of
endogenous rhythms.
PMID- 29940800
TI - TNFAIP3-DEPTOR complex regulates inflammasome secretion through autophagy in
ankylosing spondylitis monocytes.
AB - Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease with
severe inflammatory symptoms in the axial skeleton. The cause of ankylosing
spondylitis is unknown. TNFAIP3, also named A20, uses ubiquitin-related functions
to regulate immune activation, deficiency of which is highly related to
autoimmune disease. However, the role of TNFAIP3 in human AS has not been
reported. Our objective was to study the role and mechanism of TNFAIP3 in
ankylosing spondylitis. TNFAIP3 expression on different types of immunocytes from
AS peripheral blood was measured by flow cytometry. In vitro, monocytes were
transfected with a TNFAIP3 shRNA lentivirus, and IL6 and IL1B activation was
tested using real-time PCR and ELISA. The novel interaction complex TNFAIP3
DEPTOR was determined through GST pull-down, yeast two-hybrid system, confocal
microscopy, and co-immunoprecipitation. Transmission electron microscopy, the RFP
GFP-LC3 adenovirus, and LC3 expression were used for autophagy detection. Here,
we show that TNFAIP3 expression in AS peripheral blood non-classical monocytes
was decreased. In normal monocytes, TNFAIP3 induced autophagy, which restricted
inflammasome activation to the early stage of LPS stimulation. Zinc-finger
domains of TNFAIP3 were able to interact and stabilize DEPTOR. TNFAIP3 and DEPTOR
together rapidly promoted autophagy after LPS treatment to prevent NLRP3
inflammasome formation. Finally, TNFAIP3 and DEPTOR deficiency in AS non
classical monocytes facilitated inflammasome activation. Our study indicates that
TNFAIP3-DEPTOR complex-induced early-onset autophagy is vital for immune
inhibition in autoimmune disease.
PMID- 29940802
TI - The evolution and rise of stereotactic body radiotherapy (SBRT) for spinal
metastases.
AB - INTRODUCTION: Owing to improvements in clinical care and systemic therapy, more
patients are being diagnosed with, and living longer with, spinal metastases
(SM). In parallel, tremendous technological progress has been made in the field
of radiation oncology. Advances in both software and hardware are able to
integrate three- (and four-) dimensional body imaging with spatially accurate
treatment delivery methods. This leads to improved efficacy, shortened treatment
schedule, and potentially reduced treatment-related toxicity. Areas covered: In
this review, we will look at the progress made by stereotactic body radiotherapy
(SBRT) in the management of SM. We will review the technological factors which
have enabled the widespread use of SBRT. The efficacy of SBRT, in various
clinical scenarios, and associated toxicities will be reviewed. Lastly, we will
discuss about patient selection and provide a five-year roadmap. Expert
commentary: Spine SBRT is a safe and efficacious treatment option. Practice
guidelines recommend the use of SBRT in oligometastatic patients especially those
with radio-resistant cancer types, and in scenarios involving re-irradiation.
SBRT offers patients dose-intensification over a short schedule which may allow
less time off systemic therapy. The results of the phase III trials are eagerly
awaited.
PMID- 29940803
TI - Theory of mind ability in high socially anxious individuals.
AB - BACKGROUND/OBJECTIVES: Research has demonstrated an association between social
anxiety and impaired Theory of Mind (ToM). We assess whether ToM deficits occur
even at a subclinical level of social anxiety and whether group differences in
ToM performance are consistent with interpretation bias. We also explore
potential reasons as to why socially anxious individuals may perform differently
on ToM tasks. METHODS/DESIGN: Undergraduate participants high (HSA; n = 78) and
low (LSA; n = 35) in social anxiety completed a task of ToM decoding, the Reading
the Mind in the Eyes (MIE), a task of ToM reasoning, the Movie for the Assessment
of Social Cognition (MASC), and a post-task questionnaire about their experience
completing the MASC. RESULTS: HSAs performed marginally worse than LSAs on the
MIE on neutrally valenced trials, and their pattern of errors may be consistent
with a negative interpretation bias. HSAs and LSAs did not differ overall in
performance on the MASC, though HSAs reported experiencing more confusion and
distress than LSAs during the task, and this distress was associated with more
MASC errors for HSA participants only. These results provide insight into the
nature of ToM ability in socially anxious individuals and highlight important
avenues for future research.
PMID- 29940804
TI - Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to late
endosomes.
AB - Rab2 is a conserved Rab GTPase with a well-established role in secretory pathway
function and phagocytosis. Here we demonstrate that Drosophila Rab2 is recruited
to late endosomal membranes, where it controls the fusion of LAMP-containing
biosynthetic carriers and lysosomes to late endosomes. In contrast, the lysosomal
GTPase Gie/Arl8 is only required for late endosome-lysosome fusion, but not for
the delivery of LAMP to the endocytic pathway. We also find that Rab2 is required
for the fusion of autophagosomes to the endolysosomal pathway, but not for the
biogenesis of lysosome-related organelles. Surprisingly, Rab2 does not rely on
HOPS-mediated vesicular fusion for recruitment to late endosomal membranes. Our
work suggests that Drosophila Rab2 is a central regulator of the endolysosomal
and macroautophagic/autophagic pathways by controlling the major heterotypic
fusion processes at the late endosome.
PMID- 29940805
TI - CD19-targeted immunotherapies for treatment of patients with non-Hodgkin B-cell
lymphomas.
AB - INTRODUCTION: Ubiquitous expression of CD19 on B cell non-Hodgkin lymphoma
identified it as a potential target for immune-based therapies. Areas covered:
This article reviews the current literature on anti-CD19 therapies currently in
clinical trials including monoclonal antibodies (mAb), antibody targeted
cytotoxic drug conjugates (ADC), bispecific antibodies, and chimeric antigen
receptor (CAR) modified T cells. Expert opinion: Naked anti-CD19 mAbs have shown
little clinical benefit in B cell lymphomas. Despite unusual toxicity profiles
with many anti-CD19 ADCs slowing development, durable remissions in a substantial
minority of patients with refractory aggressive lymphomas should encourage
continued efforts in this area. Blinatumomab, an anti-CD19 bispecific T cell
engager, has shown impressive responses in relapse/refractory diffuse large B
cell lymphoma (DLBCL), but is plagued by neurotoxicity issues and the need for
continuous infusion. CD19 targeting CAR-T cell therapies are the most promising,
with the potential for curing a third of refractory DLBCL patients. There is
still much work to be done to address potentially life-threatening cytokine
release syndrome and neurotoxicity, an extended production time precluding
patients with rapidly progressive disease, and treatment expense. However, if the
promise of CAR-T cell technology is confirmed, this will likely change the
approach and prognosis for relapse/refractory aggressive lymphoma.
PMID- 29940806
TI - Developmentally regulated autophagy is required for eye formation in Drosophila.
AB - : The compound eye of the fruit fly Drosophila melanogaster is one of the most
intensively studied and best understood model organs in the field of
developmental genetics. Herein we demonstrate that autophagy, an evolutionarily
conserved selfdegradation process of eukaryotic cells, is essential for eye
development in this organism. Autophagic structures accumulate in a specific
pattern in the developing eye disc, predominantly in the morphogenetic furrow
(MF) and differentiation zone. Silencing of several autophagy genes (Atg) in the
eye primordium severely affects the morphology of the adult eye through
triggering ectopic cell death. In Atg mutant genetic backgrounds however genetic
compensatory mechanisms largely rescue autophagic activity in, and thereby normal
morphogenesis of, this organ. We also show that in the eye disc the expression of
a key autophagy gene, Atg8a, is controlled in a complex manner by the anterior
Hox paralog Lab (Labial), a master regulator of early development. Atg8a
transcription is repressed in front of, while activated along, the MF by Lab. The
amount of autophagic structures then remains elevated behind the moving MF. These
results indicate that eye development in Drosophila depends on the cell death
suppressing and differentiating effects of the autophagic process. This novel,
developmentally regulated function of autophagy in the morphogenesis of the
compound eye may shed light on a more fundamental role for cellular self
digestion in differentiation and organ formation than previously thought.
ABBREVIATIONS: alphaTub84B, alpha-Tubulin at 84B; Act5C, Actin5C; AO, acridine
orange; Atg, autophagy-related; Ato, Atonal; CASP3, caspase 3; Dcr-2; Dicer-2;
Dfd, Deformed; DZ, differentiation zone; eGFP, enhanced green fluorescent
protein; EM, electron microscopy; exd, extradenticle; ey, eyeless; FLP, flippase
recombinase; FRT, FLP recognition target; Gal4, gene encoding the yeast
transcription activator protein GAL4; GFP, green fluorescent protein; GMR, Glass
multimer reporter; Hox, homeobox; hth, homothorax; lab, labial; L3F, L3 feeding
larval stage; L3W, L3 wandering larval stage; lf, loss-of-function; MAP1LC3,
microtubule-associated protein 1 light chain 3; MF, morphogenetic furrow; PE,
phosphatidylethanolamine; PBS, phosphate-buffered saline; PI3K/PtdIns3K, class
III phosphatidylinositol 3-kinase; PZ, proliferation zone; Ref(2)P, refractory to
sigma P, RFP, red fluorescent protein; RNAi, RNA interference; RpL32, Ribosomal
protein L32; RT-PCR, reverse transcription-coupled polymerase chain reaction;
S.D., standard deviation; SQSTM1, Sequestosome-1, Tor, Target of rapamycin;
TUNEL, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling
assay; UAS, upstream activation sequence; qPCR, quantitative real-time polymerase
chain reaction; w, white.
PMID- 29940808
TI - The role of imaging and biopsy in the management and staging of large non
pedunculated rectal polyps.
AB - INTRODUCTION: Endoscopic mucosal resection (EMR) and endoscopic submucosal
dissection (ESD) are often used for benign and Sm1 large non-pedunculated rectal
polyps (LNPRPs), although other surgical techniques including transanal
endoscopic microsurgery (TEMS) and transanal minimal invasive surgery remain
available. This review covers the role of pre-excisional imaging and selective
biopsy of LNPRPs. Areas covered: Polyps between 2 and 3 cm with favorable
features (Paris 1, Kudo III/IV pit patterns, and non-lateral spreading type
[LST]) may have a one-stage EMR without biopsy and imaging, provided adequate
expertise is available with other technologies such as magnifying
chromoendoscopy. Higher-risk polyps (moderate/severe dysplasia, 0-IIa+c
morphology, nongranular LST, Kudo pit pattern V or submucosal carcinoma, or those
>3 cm) should have pre-EMR/ESD imaging with magnetic resonance imaging (MRI)
and/or endorectal ultrasound (ERUS) +/- biopsies and photographs prior to
multidisciplinary team discussion. Expert commentary: In some centers, EMR and
ESD are considered the primary modality of treatment, with TEMS as a back-up,
while elsewhere, TEMS is the main modality for excision of significant polyps and
early colorectal cancer lesions. Likewise, the exact roles of ERUS and MRI will
depend on availability of local expertise, although it is suggested that the
techniques are complementary.
PMID- 29940807
TI - TRIM37 deficiency induces autophagy through deregulating the MTORC1-TFEB axis.
AB - : TRIM37 gene mutations cause mulibrey (muscle-liver-brain-eye) nanism, a severe
growth disorder with prenatal onset. Although TRIM37 depletion normally induces
apoptosis, patients with TRIM37 mutations have a high risk of developing tumors,
suggesting that there may be an alternative pro-survival mechanism for TRIM37
deficient tumor cells. We find that TRIM37 interacts with MTOR and RRAGB
proteins, enhances the MTOR-RRAGB interaction and promotes lysosomal localization
of MTOR, thereby activating amino acid-stimulated MTORC1 signaling. In response
to loss of TRIM37 functions, phosphorylation of TFEB is significantly reduced,
resulting in its translocation into the nucleus enabling its transcriptional
activation of genes involved in lysosome biogenesis and macroautophagy/autophagy.
The enhanced autophagy depends on the inhibition of MTORC1 signaling and may
serve as an alternative mechanism to survive the loss of TRIM37 functions. Our
study unveils a positive role of TRIM37 in regulating the MTORC1-TFEB axis and
provides mechanistic insights into the pathogenesis of mulibrey nanism, as well
as potential therapeutic treatment. ABBREVIATIONS: ACTB: actin beta; ATG:
autophagy related; CASP3: caspase3; CLEAR: coordinated lysosomal expression and
regulation; CQ: chloroquine; CTS: cathepsin proteases; CTSL: cathepsin L;
EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; LAMP1:
lysosomal associated membrane protein 1; LAMP2: lysosomal associated membrane
protein 2; LMNB1: lamin B1; MAP1LC3B/LC3B: microtubule associated protein 1 light
chain 3 beta; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex
1; mulibrey: muscle-liver-brain-eye; NAC: N-acetyl-L-cysteine; PARP1: poly(ADP
ribose) polymerase 1; RAP2A: member of RAS oncogene family; RHEB: Ras homolog
enriched in brain; ROS: reactive oxygen species; RPS6KB1: ribosomal protein S6
kinase B1; RRAGB: Ras related GTP binding B; SQSTM1: sequestosome 1; TFEB:
transcription factor EB; TRIM37: tripartite motif containing 37.
PMID- 29940809
TI - Schiff base-containing dextran nanogel as pH-sensitive drug delivery system of
doxorubicin: Synthesis and characterization.
AB - Stimuli-responsive hydrogels have been widely researched as carrier systems, due
to their excellent biocompatibility and responsiveness to external physiologic
environment factors. In this study, dextran-based nanogel with covalently
conjugated doxorubicin (DOX) was developed via Schiff base formation using the
inverse microemulsion technique. Since the Schiff base linkages are acid
sensitive, drug release profile of the DOX-loaded nanogel would be pH-dependent.
In vitro drug release studies confirmed that DOX was released much faster under
acidic condition (pH 2.0, 5.0) than that at pH 7.4. Approximately 66, 28, and 9%
of drug was released in 72 h at pH 2.0, 5.0, and 7.4, respectively. Cell uptake
by the human breast cancer cell (MCF-7) demonstrated that the DOX-loaded dextran
nanogel could be internalized through endocytosis and distributed in endocytic
compartments inside tumor cells. These results indicated that the Schiff base
containing nanogel can serve as a pH-sensitive drug delivery system. And the
presence of multiple aldehyde groups on the nanogel are available for further
conjugations of targeting ligands or imaging probes.
PMID- 29940811
TI - Preparing nurses to be prescribers of digital therapeutics.
PMID- 29940810
TI - Radiomics for Response and Outcome Assessment for Non-Small Cell Lung Cancer.
AB - Routine follow-up visits and radiographic imaging are required for outcome
evaluation and tumor recurrence monitoring. Yet more personalized surveillance is
required in order to sufficiently address the nature of heterogeneity in nonsmall
cell lung cancer and possible recurrences upon completion of treatment.
Radiomics, an emerging noninvasive technology using medical imaging analysis and
data mining methodology, has been adopted to the area of cancer diagnostics in
recent years. Its potential application in response assessment for cancer
treatment has also drawn considerable attention. Radiomics seeks to extract a
large amount of valuable information from patients' medical images (both
pretreatment and follow-up images) and quantitatively correlate image features
with diagnostic and therapeutic outcomes. Radiomics relies on computers to
identify and analyze vast amounts of quantitative image features that were
previously overlooked, unmanageable, or failed to be identified (and recorded) by
human eyes. The research area has been focusing on the predictive accuracy of
pretreatment features for outcome and response and the early discovery of signs
of tumor response, recurrence, distant metastasis, radiation-induced lung injury,
death, and other outcomes, respectively. This review summarized the application
of radiomics in response assessments in radiotherapy and chemotherapy for non
small cell lung cancer, including image acquisition/reconstruction, region of
interest definition/segmentation, feature extraction, and feature selection and
classification. The literature search for references of this article includes
PubMed peer-reviewed publications over the last 10 years on the topics of
radiomics, textural features, radiotherapy, chemotherapy, lung cancer, and
response assessment. Summary tables of radiomics in response assessment and
treatment outcome prediction in radiation oncology have been developed based on
the comprehensive review of the literature.
PMID- 29940812
TI - p75 Neurotrophin Receptor: A Double-Edged Sword in Pathology and Regeneration of
the Central Nervous System.
AB - The low-affinity nerve growth factor receptor p75NTR is a major neurotrophin
receptor involved in manifold and pleiotropic functions in the developing and
adult central nervous system (CNS). Although known for decades, its entire
functions are far from being fully elucidated. Depending on the complex
interactions with other receptors and on the cellular context, p75NTR is capable
of performing contradictory tasks such as mediating cell death as well as cell
survival. In parallel, as a prototype marker for certain differentiation stages
of Schwann cells and related CNS aldynoglial cells, p75NTR has recently gained
increasing notice as a marker for cells with proposed regenerative potential in
CNS diseases, such as demyelinating disease and traumatic CNS injury. Besides its
pivotal role as a marker for transplantation candidate cells, recent studies in
canine neuroinflammatory CNS conditions also highlight a spontaneous endogenous
occurrence of p75NTR-positive glia, which potentially play a role in Schwann cell
mediated CNS remyelination. The aim of the present communication is to review the
pleiotropic functions of p75NTR in the CNS with a special emphasis on its role as
an immunohistochemical marker in neuropathology. Following a brief illustration
of the expression of p75NTR in neurogenesis and in developed neuronal
populations, the implications of p75NTR expression in astrocytes,
oligodendrocytes, and microglia are addressed. A special focus is put on the role
of p75NTR as a cell marker for specific differentiation stages of Schwann cells
and a regeneration-promoting CNS population, collectively referred to as
aldynoglia.
PMID- 29940813
TI - Cerebral Liposarcoma Embolus From Heart Metastasis Successfully Treated by
Endovascular Extraction Followed by Cardiac Surgery.
AB - The current case presents a patient with a tumor emboli stroke as a presenting
symptom of a liposarcoma metastasis to the heart that was treated successfully
with endovascular mechanical retrieval, followed by subsequent cardiac surgery.
The patient is still alive, under chemotherapy treatment, 3 years following the
interventions. This scenario should be considered as a part of the differential
diagnosis of oncology patients presenting with new central neurological symptoms.
This active approach can be an effective treatment if the patient is fit and
there is no evidence of widespread disease.
PMID- 29940814
TI - Optimal Treatment for Ruptured Pancreaticoduodenal Artery Aneurysm Caused by
Celiac Artery Obstruction Due to Celiac Artery Dissection.
AB - A pancreaticoduodenal artery (PDA) aneurysm develops due to increased flow
through the pancreaticoduodenal arcade in the setting of celiac or superior
mesenteric artery occlusion. Additionally, there is no evidence on the computed
tomography scan or angiography images that the dissection process extends to the
PDA arcade. Moreover, the optimal treatment protocols for PDA aneurysms with
celiac artery obstruction and for celiac artery dissection are controversial. We
report 2 cases of ruptured PDA aneurysms caused by celiac artery obstruction due
to celiac artery dissection in which the aneurysm was excluded, but celiac artery
revascularization was not performed successfully. Our cases indicate that
endovascular management for ruptured PDA aneurysms and conservative management
for celiac artery obstruction due to celiac artery dissection are feasible as
first-line treatment in such cases.
PMID- 29940815
TI - Pneumonia in a Captive Central Bearded Dragon With Concurrent Detection of
Helodermatid Adenovirus 2 and a Novel Mycoplasma Species.
AB - A 4-year-old captive male central bearded dragon ( Pogona vitticeps) was
presented for recurrent episodic dyspnea and anorexia with occasional expulsion
of oral mucoid discharge. Despite empirical antimicrobial therapy and supportive
care, the animal died and was submitted for autopsy. Defining histologic features
included heterophilic and lymphocytic interstitial pneumonia, with occasional
amphophilic intranuclear inclusions and prominent type II pneumocyte hyperplasia.
Transmission electron microscopy revealed intranuclear 80-nm, nonenveloped,
hexagonal viral particles within pneumocytes. Helodermatid adenovirus 2 (HeAdV2)
was determined as the etiologic agent through pan-adenoviral consensus polymerase
(PCR) chain reaction and sequencing. Nucleic acid from a novel Mycoplasma sp.
(provisionally called Mycoplasma pogonae) was identified by pan-generic PCR
targeting the mycoplasma 16S ribosomal RNA gene with sequencing and phylogenetic
analysis. As bacteria morphologically consistent with Mycoplasma sp. were not
observed by special stains and transmission electron microscopy, the detection of
M. pogonae nucleic acid is of indeterminate significance; however, M. pogonae and
HeAdV2 coinfection may have exacerbated disease.
PMID- 29940816
TI - Splenic Artery Aneurysm Treated With Endovascular Stent Grafting: A Case Report
and Review of Literature.
AB - INTRODUCTION:: Although endovascular therapy is becoming an alternative to open
surgical repair of splenic artery aneurysms (SAAs), reports on the use of stent
grafts for SAA repair are limited. We present our experience of endovascular
therapy using a stent graft for the treatment of an SAA that had ruptured into
the gastric lumen. We also reviewed 18 cases of stent graft repair for SAAs,
including the present case. CASE REPORT:: A 43-year-old man was admitted due to
hematemesis. Endoscopic examination and contrast-enhanced computed tomography
(CT) revealed a dissecting SAA that had ruptured into the stomach. Two 10 * 100
mm Viabahn (W.L. Gore, Flagstaff, Arizona) stent grafts were used to exclude the
aneurysm. No complications occurred during the procedure. Although postoperative
CT showed complete exclusion of the aneurysm, endoscopic examination showed a
discharge of purulent matter from the aneurysm. Therefore, surgical debridement
and omental implantation were added to avoid stent graft infection. Follow-up CT
obtained 1 year later showed the residual aneurysm almost disappeared without any
evidence of infection. LITERATURE REVIEW:: A literature search in the PubMed
database returned 17 cases with sufficient data. Review of these cases, together
with the present case, revealed a 100% technical success rate, 11% splenic
infarction rate, 94% graft patency rate, and 0% reintervention rate. CONCLUSION::
Endovascular repair of SAAs using stent grafts appears to be safe and effective.
In terms of preserving the blood flow and avoiding splenic infarction, it may be
superior to coil embolization. Even in a case with aneurysm infection, stent
graft repair may be an acceptable method to minimize invasion of concomitant
surgical intervention.
PMID- 29940818
TI - Picking an apple from a tree: Response-selection demands, inhibition
requirements, and the functionality of the Quiet Eye in a far-aiming task.
AB - In the study of the mutual coupling between perception and action, the
performance-enhancing effect of the last fixation before movement initiation, the
Quiet Eye (QE), has been repeatedly shown. To the explanation of this phenomenon,
among others, an inhibition hypothesis was formulated which suggests that the
parametrisation of the optimal task solution is shielded against non-optimal task
solutions. In this study, a prediction of this hypothesis was tested by
manipulating response-selection demands over movement preparation in a targeting
task which required to throw balls as accurate as possible at virtual target
discs. Participants in the group with high response-selection demands always had
to select one out of four targets, whereas the selection for the participants in
the group with low response-selection demands was yoked to the selection of the
other group. The results showed the predicted longer QE durations for the high
response-selection demands group that, particularly, emanated from earlier QE
onsets. Because of similar throwing demands, these differences cannot merely be
explained by differences in the fine-tuning of the motor response but provide
evidence for the suggested inhibition function. Particularly, with high response
selection demands, the parametrisation of the non-selected targets over movement
preparation had to be inhibited. Descriptively, differences in the QE offset
suggest that these shielding requirements persisted over movement control. This
study extends earlier work on the theoretical foundation of the QE phenomenon and
provides fruitful insights into its underlying mechanisms.
PMID- 29940817
TI - The Correlation Between TNF-alpha Promoter Gene Polymorphism and Genetic
Susceptibility to Cervical Cancer.
AB - To investigate the association between the susceptibility to cervical cancer and
the single nucleotide polymorphisms of 5 tumor necrosis factor-alpha promoter
genes (rs361525, rs1800629, rs1800750, rs1799964, and rs673) in Chinese women. A
total of 946 peripheral blood samples were collected from women of Han Ethnicity
in Shandong province. Of them, 452 were diagnosed with cervical squamous cell
carcinomas. The study also included a control group of 494 healthy women. The
targeted single nucleotide polymorphisms were analyzed by TaqMan probe method.
(1) The rate of high-risk subtype human papillomavirus infection in exfoliated
cervical epithelial cells was significantly higher in patients with cervical
cancer than the control group (91.4% vs 10.3%, P < .01). The rate of human
papillomavirus infection was lower in patients with carcinoma in situ than those
with invasive carcinoma (77.9% vs 95.4%, P < .01). (2) There was a significant
difference for rs361525 genotype (CC/CT/TT) between the control, carcinoma in
situ, and invasive carcinoma groups ( P < .001). Both rs1800629 and rs1799964
genotypes (both GG/GA/AA) were also different between these groups ( P < .001 and
P < .001). (3) The allele frequencies of rs361525, rs1800629, and rs1799964 were
significantly correlated with the diagnosis of cervical cancer. The frequency of
T allele in rs361525 was significantly higher for cervical cancer group (10.8%)
than control group (3.8%; odds ratio = 3.04, 95% confidence interval = 1.76-5.25,
P < .01). The frequency of A allele in rs1800629 was significantly higher for
cervical cancer (29.9%) than control group (14.2%; odds ratio = 2.58, 95%
confidence interval = 1.87-3.56, P < .01). The frequency of A allele in rs1799964
was also higher for cervical cancer group (38.3%) than control group (16.4%; odds
ratio = 1.43, 95% confidence interval = 1.07-1.91, P < .05). The rs361525,
rs1800629, and rs17999645 were significantly correlated with the diagnosis of
cervical cancer.
PMID- 29940820
TI - Reimbursement for School Nursing Services: Position Statement.
PMID- 29940821
TI - Preparation: A Key Leadership Principle.
PMID- 29940819
TI - Investigation of Plasma Inflammatory Profile in Diabetic Patients With Abdominal
Aortic Aneurysm: A Pilot Study.
AB - INTRODUCTION:: Clinical studies have unraveled a negative association between
diabetes and abdominal aortic aneurysm (AAA), but the mechanisms involved are
still poorly understood. The aim of this study was to determine whether diabetic
patients with AAA had a distinct plasma inflammatory profile compared to
nondiabetic patients. METHODS:: Plasma samples were obtained from 10 diabetic
patients with AAA and 10 nondiabetic patients with AAA. The relative protein
expression of 92 inflammatory-related human protein biomarkers was assessed by
proximity extension assay technology using Proseek Multiplex Inflammation I kit
(Olink). RESULTS:: Clinical characteristics were similar in diabetic patients
with AAA compared to nondiabetic patients with AAA, the median ages being 67 and
73 years, respectively ( P = .61). The AAA diameters were, respectively, 50 and
49 mm ( P = .72). Among the 92 markers screened, 67 (72.8%) were detected in all
samples. Diabetic patients had significantly lower protein expression of C-C
motif chemokine 19 (CCL19) and C-C motif chemokine 23 (CCL23; 542.3 vs 980.3, P =
.01 and 1236 vs 1406, P = .04, respectively). They tended to have higher
expression of tumor necrosis factor ligand superfamily member 14 (TNFSF14)
compared to controls (14.6 vs 10.8, P = .05). CONCLUSION:: Diabetic patients with
AAA differentially expressed CCL19, CCL23 and TNFSF14 in plasma compared to
nondiabetic patients with AAA. Further studies are required to determine whether
the markers identified could play a role in the negative association between
diabetes and AAA pathogenesis.
PMID- 29940823
TI - Letter to the Editor.
PMID- 29940822
TI - NASN's Legislative Priorities.
PMID- 29940824
TI - Causal inference for long-term survival in randomised trials with treatment
switching: Should re-censoring be applied when estimating counterfactual survival
times?
AB - Treatment switching often has a crucial impact on estimates of effectiveness and
cost-effectiveness of new oncology treatments. Rank preserving structural failure
time models (RPSFTM) and two-stage estimation (TSE) methods estimate
'counterfactual' (i.e. had there been no switching) survival times and
incorporate re-censoring to guard against informative censoring in the
counterfactual dataset. However, re-censoring causes a loss of longer term
survival information which is problematic when estimates of long-term survival
effects are required, as is often the case for health technology assessment
decision making. We present a simulation study designed to investigate
applications of the RPSFTM and TSE with and without re-censoring, to determine
whether re-censoring should always be recommended within adjustment analyses. We
investigate a context where switching is from the control group onto the
experimental treatment in scenarios with varying switch proportions, treatment
effect sizes, treatment effect changes over time, survival function shapes,
disease severity and switcher prognosis. Methods were assessed according to their
estimation of control group restricted mean survival that would be observed in
the absence of switching, up to the end of trial follow-up. We found that
analyses which re-censored usually produced negative bias (i.e. underestimating
control group restricted mean survival and overestimating the treatment effect),
whereas analyses that did not re-censor consistently produced positive bias which
was often smaller in magnitude than the bias associated with re-censored
analyses, particularly when the treatment effect was high and the switching
proportion was low. The RPSFTM with re-censoring generally resulted in increased
bias compared to the other methods. We believe that analyses should be conducted
with and without re-censoring, as this may provide decision-makers with useful
information on where the true treatment effect is likely to lie. Incorporating re
censoring should not always represent the default approach when the objective is
to estimate long-term survival times and treatment effects.
PMID- 29940827
TI - "They Say I Should not Think About It:": A Qualitative Study Exploring the
Experience of Infant Loss for Bereaved Mothers in Kumasi, Ghana.
AB - Despite the high rate of infant mortality in Ghana, few studies have explored the
maternal experience of infant loss and the perinatal grieving process. As part of
a larger study that interviewed 153 mothers with a sick infant, this 1-year
follow-up study reinterviewed eight mothers from the original cohort whose infant
died since the study began. Mothers were queried about mental health, coping, and
cultural issues related to the loss. Mothers were often discouraged from speaking
or thinking about the death due to fear of psychological harm and impact on
fertility. Primary coping mechanisms involved seeking support within the
community and accepting the loss as God's will. Mothers desired more
communication from health-care providers at the time of death. Despite the
cultural norm of silent acceptance in the face of perinatal loss, intense
maternal grief and desire to mourn may allow more opportunities for health-care
workers to support bereaved mothers.
PMID- 29940828
TI - R.I.P. Kutner: Parasocial Grief Following the Death of a Television Character.
AB - In 2009, Lawrence Kutner, a character on television's House, M.D., unexpectedly
committed suicide. A Facebook memorial group was created shortly thereafter in
memory of the fictional character. A thematic analysis of fan postings on
Kutner's Facebook memorial page revealed evidence of people experiencing
parasocial grief as they displayed emotional expressions of grief, reminisced,
and advocated for Kutner. Through thematic analysis, we discovered that elements
of parasocial relationships, particularly parasocial breakups, were apparent as
the members posted evidence of their grief over the loss of a television
character. Moreover, this parasocial grief is likely to be disenfranchised, as
the death of a television character is typically not recognized by others as a
legitimate loss. This study also highlighted the role of social media as an
outlet for grief as well as revealed confusion between fiction and reality
resulting from social media.
PMID- 29940829
TI - The New Forms of Mourning: Loss and Exhibition of the Death on the Internet.
AB - According to some specialists, ceremonial funeral practices are inclined to
disappear, particularly as death is an object of repression in contemporary
society. However, it seems that new forms of rituals are developing through
modern technologies. Virtual tombs, memorial webpages, and the celebration of
death anniversaries are now common currency on the Internet. Nonetheless, the
overexposure favored by the Web seems to question traditional ways of "living
out" one's grief, subjecting the living and the dead to a redefinition of
concepts of time and space, and entailing new forms of interaction.
PMID- 29940830
TI - Dealing With the Concepts of "Grief" and "Grieving" in the Classroom: Children's
Perceptions, Emotions, and Behavior.
AB - This article presents an action research study that explores how a fifth-grade
classroom of 10- to 11-year-old children in Cyprus perceive the concepts of grief
and grieving, after an educational intervention provided space for discussing
such issues. It also explores the impact that the intervention program had on
children's emotions while exploring these concepts and illustrates how it
affected their behavior. The findings suggest that the intervention had a
constructive impact on children's understandings of grief and grieving along two
important dimensions. First, the intervention helped children better define
emotional responses to loss (grief). Second, children seemed to overcome their
anxiety while talking about grief and grieving and were able to share relevant
personal experiences. The study has important implications for curriculum
development, pedagogical practice, and teacher training on death education.
PMID- 29940831
TI - The Role of Self-Esteem in Suicides Among Young Men.
AB - This study explores self-esteem in suicide among young males with no earlier
history of suicide attempt(s) or treatment in mental health services. The data
come from an ongoing psychological autopsy study; 10 cases of young men aged 18
to 30, were selected to generate a phenomenologically based understanding of the
psychological mechanisms and processes involved in the suicidal process. The
analyses are based on in-depth interviews with 61 closely connected individuals,
as well as suicide notes. We used Interpretative Phenomenological Analysis. For
these young men, the transition to young adulthood, a period of major life
challenges, seemed to be associated with personal defeats. According to their
significant others, the deceased seemed to have experienced intolerable
discrepancies between their actual performances and their ideal self standards.
Four themes emerged from the analysis: (a) striving to find a viable path to life
as an adult man; (b) experiencing a sense of failure according to own standards;
(c) emotional self-restriction in relationships; and (d) strong feelings of
loneliness and rejection of self. Improved understanding of suicides outside the
mental illness paradigm may have important implications for preventive
strategies.
PMID- 29940832
TI - The Site of Bone Marrow Acquisition Affects the Myeloid to Erythroid Ratio in
Apparently Healthy Dogs.
AB - Bone marrow (BM) cytology and histopathology are complementary tools used to
investigate hematological diseases. The purpose of this study was to determine if
there are site-dependent differences in the diagnostic quality, myeloid to
erythroid ratio (MER), and discordant findings in samples from different sites in
the same dog. Eighteen apparently healthy dogs were used in the study. The
sequence of sample acquisition was randomized according to a Latin square, and
samples for BM cytology and histology were collected from both humeri and both
ilial crests immediately after death. Board-certified clinical and anatomical
pathologists read the cytology and histology, respectively. The data were
analyzed using a mixed-effect model. The site of BM acquisition did not affect BM
sample quality. The rate of discordant clinical findings between sites was 0.05
(95% confidence interval, 0.01-0.13). In general, by cytology, the MERs were
slightly but significantly greater in samples from the ilial crests than from the
humeri ( P = .01). The measured MER for histology was nearly twice that for
cytology for all sites ( P < .001). In conclusion, there was a low-rate, site
dependent discordance in diagnostic findings in BM samples and differences in MER
between the ilial crest and the humerus. A similar study is justified in sick
dogs with hematological disease to determine the effect of sampling site on
discordant findings between sites.
PMID- 29940833
TI - AUCTSP: an improved biomarker gene pair class predictor.
AB - BACKGROUND: The Top Scoring Pair (TSP) classifier, based on the concept of
relative ranking reversals in the expressions of pairs of genes, has been
proposed as a simple, accurate, and easily interpretable decision rule for
classification and class prediction of gene expression profiles. The idea that
differences in gene expression ranking are associated with presence or absence of
disease is compelling and has strong biological plausibility. Nevertheless, the
TSP formulation ignores significant available information which can improve
classification accuracy and is vulnerable to selecting genes which do not have
differential expression in the two conditions ("pivot" genes). RESULTS: We
introduce the AUCTSP classifier as an alternative rank-based estimator of the
magnitude of the ranking reversals involved in the original TSP. The proposed
estimator is based on the Area Under the Receiver Operating Characteristic (ROC)
Curve (AUC) and as such, takes into account the separation of the entire
distribution of gene expression levels in gene pairs under the conditions
considered, as opposed to comparing gene rankings within individual subjects as
in the original TSP formulation. Through extensive simulations and case studies
involving classification in ovarian, leukemia, colon, breast and prostate cancers
and diffuse large b-cell lymphoma, we show the superiority of the proposed
approach in terms of improving classification accuracy, avoiding overfitting and
being less prone to selecting non-informative (pivot) genes. CONCLUSIONS: The
proposed AUCTSP is a simple yet reliable and robust rank-based classifier for
gene expression classification. While the AUCTSP works by the same principle as
TSP, its ability to determine the top scoring gene pair based on the relative
rankings of two marker genes across all subjects as opposed to each individual
subject results in significant performance gains in classification accuracy. In
addition, the proposed method tends to avoid selection of non-informative (pivot)
genes as members of the top-scoring pair.
PMID- 29940834
TI - Multiobjective grammar-based genetic programming applied to the study of asthma
and allergy epidemiology.
AB - BACKGROUND: Asthma and allergies prevalence increased in recent decades, being a
serious global health problem. They are complex diseases with strong contextual
influence, so that the use of advanced machine learning tools such as genetic
programming could be important for the understanding the causal mechanisms
explaining those conditions. Here, we applied a multiobjective grammar-based
genetic programming (MGGP) to a dataset composed by 1047 subjects. The dataset
contains information on the environmental, psychosocial, socioeconomics,
nutritional and infectious factors collected from participating children. The
objective of this work is to generate models that explain the occurrence of
asthma, and two markers of allergy: presence of IgE antibody against common
allergens, and skin prick test positivity for common allergens (SPT). RESULTS:
The average of the accuracies of the models for asthma higher in MGGP than C4.5.
IgE were higher in MGGP than in both, logistic regression and C4.5. MGGP had
levels of accuracy similar to RF, but unlike RF, MGGP was able to generate models
that were easy to interpret. CONCLUSIONS: MGGP has shown that infections,
psychosocial, nutritional, hygiene, and socioeconomic factors may be related in
such an intricate way, that could be hardly detected using traditional regression
based epidemiological techniques. The algorithm MGGP was implemented in c ++ and
is available on repository: http://bitbucket.org/ciml-ufjf/ciml-lib .
PMID- 29940835
TI - WHAM!: a web-based visualization suite for user-defined analysis of metagenomic
shotgun sequencing data.
AB - BACKGROUND: Exploration of large data sets, such as shotgun metagenomic sequence
or expression data, by biomedical experts and medical professionals remains as a
major bottleneck in the scientific discovery process. Although tools for this
purpose exist for 16S ribosomal RNA sequencing analysis, there is a growing but
still insufficient number of user-friendly interactive visualization workflows
for easy data exploration and figure generation. The development of such
platforms for this purpose is necessary to accelerate and streamline microbiome
laboratory research. RESULTS: We developed the Workflow Hub for Automated
Metagenomic Exploration (WHAM!) as a web-based interactive tool capable of user
directed data visualization and statistical analysis of annotated shotgun
metagenomic and metatranscriptomic data sets. WHAM! includes exploratory and
hypothesis-based gene and taxa search modules for visualizing differences in
microbial taxa and gene family expression across experimental groups, and for
creating publication quality figures without the need for command line interface
or in-house bioinformatics. CONCLUSIONS: WHAM! is an interactive and customizable
tool for downstream metagenomic and metatranscriptomic analysis providing a user
friendly interface allowing for easy data exploration by microbiome and
ecological experts to facilitate discovery in multi-dimensional and large-scale
data sets.
PMID- 29940836
TI - Detecting Succinylation sites from protein sequences using ensemble support
vector machine.
AB - BACKGROUND: Lysine succinylation is a new kind of post-translational modification
which plays a key role in protein conformation regulation and cellular function
control. To understand the mechanism of succinylation profoundly, it is necessary
to identify succinylation sites in proteins accurately. However, traditional
methods, experimental approaches, are labor-intensive and time-consuming.
Computational prediction methods have been proposed recent years, and they are
popular because of their convenience and high speed. In this study, we developed
a new method to predict succinylation sites in protein combining multiple
features, including amino acid composition, binary encoding, physicochemical
property and grey pseudo amino acid composition, with a feature selection scheme
(information gain). And then, it was trained using SVM (Support Vector Machine)
and an ensemble learning algorithm. RESULTS: The performance of this method was
measured with an accuracy of 89.14% and a MCC (Matthew Correlation Coefficient)
of 0.79 using 10-fold cross validation on training dataset and an accuracy of
84.5% and a MCC of 0.2 on independent dataset. CONCLUSIONS: The conclusions made
from this study can help to understand more of the succinylation mechanism. These
results suggest that our method was very promising for predicting succinylation
sites. The source code and data of this paper are freely available at
https://github.com/ningq669/PSuccE .
PMID- 29940838
TI - ProMotE: an efficient algorithm for counting independent motifs in uncertain
network topologies.
AB - BACKGROUND: Identifying motifs in biological networks is essential in uncovering
key functions served by these networks. Finding non-overlapping motif instances
is however a computationally challenging task. The fact that biological
interactions are uncertain events further complicates the problem, as it makes
the existence of an embedding of a given motif an uncertain event as well.
RESULTS: In this paper, we develop a novel method, ProMotE (Probabilistic Motif
Embedding), to count non-overlapping embeddings of a given motif in probabilistic
networks. We utilize a polynomial model to capture the uncertainty. We develop
three strategies to scale our algorithm to large networks. CONCLUSIONS: Our
experiments demonstrate that our method scales to large networks in practical
time with high accuracy where existing methods fail. Moreover, our experiments on
cancer and degenerative disease networks show that our method helps in uncovering
key functional characteristics of biological networks.
PMID- 29940837
TI - Genome-wide discovery of lincRNAs with spatiotemporal expression patterns in the
skin of goat during the cashmere growth cycle.
AB - BACKGROUND: Long intergenic noncoding RNAs (lincRNAs) have been recognized in
recent years as key regulators of biological processes. However, lincRNAs in goat
remain poorly characterized both across various tissues and during different
developmental stages in goat (Capra hircus). RESULTS: We performed the genome
wide discovery of the lincRNAs in goat by combining the RNA-seq dataset that were
generated from 28 cashmere goat skin samples and the 12 datasets of goat tissues
downloaded from the NCBI database. We identified a total of 5546 potential
lincRNA transcripts that overlapped 3641 lincRNA genes. These lincRNAs exhibited
a tissue-specific pattern. Specifically, there are 584 lincRNAs expressed
exclusively in only one tissue, and 91 were highly expressed in hair follicle
(HF). In addition, 2350 protein-coding genes and 492 lincRNAs were differentially
expressed in the skin of goat. The majority exhibited the remarkable differential
expression during the transition of the goat skin from the May-June to August
October time point, which covered the different seasons. Fundamental biological
processes, such as skin development, were significantly enriched in these genes.
Furthermore, we identified several lincRNAs highly expressed in the HF, which
exhibited not only the co-expression pattern with the key factors to the HF
development but also the activated expression in the August to October time
point. Intriguingly, one of spatiotemporal lincRNAs, linc-chig1598 could be a
potential regulator of distal-less homeobox 3 expression during the secondary
hair follicle growth. CONCLUSIONS: This study will facilitate future studies
aimed at unravelling the function of lincRNAs in hair follicle development.
PMID- 29940839
TI - Contemporaneous effects of diabetes mellitus and hypothyroidism on
spermatogenesis and immunolocalization of Claudin-11 inside the seminiferous
tubules of mice.
AB - BACKGROUND: Diabetes and hypothyroidism produce adverse effects on body weight
and sexual maturity by inhibiting body growth and metabolism. The occurrence of
diabetes is always accompanied with thyroid dysfunction. Thus, it is important to
take hypo- or hyper-thyroidism into consideration when exploring the adverse
effects caused by diabetes. Previous reports have found hypothyroidism inhibits
testicular growth by delaying Sertoli cell differentiation and proliferation.
Hence, by establishing a mouse model of diabetes combined with hypothyroidism, we
provided evidence that poly glandular autoimmune syndrome affected testicular
development and spermatogenesis. RESULTS: we mimicked polyglandular deficiency
syndrome in both immature and prepubertal mice by induction of diabetes and
hypothyroidism, which caused decreases in serum concentrations of testosterone
and insulin like growth factor 1 (IGF-1). Such reduction of growth factor
resulted in inhibition of testicular and epididymal development. Moreover,
expressions of Claudin-11 were observed between Sertoli cells and disrupted in
the testes of syndrome group mice. We also found reduced sperm count and motility
in prepubertal mice. CONCLUSIONS: This mimicry of the diabetes and thyroid
dysfunction, will be helpful to better understand the reasons for male
infertility in diabetic-cum-hypothyroid patients.
PMID- 29940841
TI - Proteome-wide analysis of human motif-domain interactions mapped on influenza a
virus.
AB - BACKGROUND: The influenza A virus (IAV) is a constant threat for humans
worldwide. The understanding of motif-domain protein participation is essential
to combat the pathogen. RESULTS: In this study, a data mining approach was
employed to extract influenza-human Protein-Protein interactions (PPI) from
VirusMentha,Virus MINT, IntAct, and Pfam databases, to mine motif-domain
interactions (MDIs) stored as Regular Expressions (RegExp) in 3DID database. A
total of 107 RegExp related to human MDIs were searched on 51,242 protein
fragments from H1N1, H1N2, H2N2, H3N2 and H5N1 strains obtained from Virus
Variation database. A total 46 MDIs were frequently mapped on the IAV proteins
and shared between the different strains. IAV kept host-like MDIs that were
associated with the virus survival, which could be related to essential
biological process such as microtubule-based processes, regulation of cell cycle
check point, regulation of replication and transcription of DNA, etc. in human
cells. The amino acid motifs were searched for matches in the immune epitope
database and it was found that some motifs are part of experimentally determined
epitopes on IAV, implying that such interactions exist. CONCLUSION: The directed
data-mining method employed could be used to identify functional motifs in other
viruses for envisioning new therapies.
PMID- 29940840
TI - Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish
parental trios.
AB - BACKGROUND: The adaptive immune response intrinsically depends on hypervariable
human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is
crucial for successful donor-patient matching in organ transplantation. The cost
and technical limitations of current laboratory techniques, together with
advances in next-generation sequencing (NGS) methodologies, have increased the
need for precise computational typing methods. RESULTS: We tested two widespread
HLA typing methods using high quality full genome sequencing data from 150
individuals in 50 family trios from the Genome Denmark project. First, we
computed descendant accuracies assessing the agreement in the inheritance of
alleles from parents to offspring. Second, we compared the locus-specific
homozygosity rates as well as the allele frequencies; and we compared those to
the observed values in related populations. We provide guidelines for testing the
accuracy of HLA typing methods by comparing family information, which is
independent of the availability of curated alleles. CONCLUSIONS: Although current
computational methods for HLA typing generally provide satisfactory results, our
benchmark - using data with ultra-high sequencing depth - demonstrates the
incompleteness of current reference databases, and highlights the importance of
providing genomic databases addressing current sequencing standards, a problem
yet to be resolved before benefiting fully from personalised medicine approaches
HLA phenotyping is essential.
PMID- 29940842
TI - BAMSI: a multi-cloud service for scalable distributed filtering of massive genome
data.
AB - BACKGROUND: The advent of next-generation sequencing (NGS) has made whole-genome
sequencing of cohorts of individuals a reality. Primary datasets of raw or
aligned reads of this sort can get very large. For scientific questions where
curated called variants are not sufficient, the sheer size of the datasets makes
analysis prohibitively expensive. In order to make re-analysis of such data
feasible without the need to have access to a large-scale computing facility, we
have developed a highly scalable, storage-agnostic framework, an associated API
and an easy-to-use web user interface to execute custom filters on large genomic
datasets. RESULTS: We present BAMSI, a Software as-a Service (SaaS) solution for
filtering of the 1000 Genomes phase 3 set of aligned reads, with the possibility
of extension and customization to other sets of files. Unique to our solution is
the capability of simultaneously utilizing many different mirrors of the data to
increase the speed of the analysis. In particular, if the data is available in
private or public clouds - an increasingly common scenario for both academic and
commercial cloud providers - our framework allows for seamless deployment of
filtering workers close to data. We show results indicating that such a setup
improves the horizontal scalability of the system, and present a possible use
case of the framework by performing an analysis of structural variation in the
1000 Genomes data set. CONCLUSIONS: BAMSI constitutes a framework for efficient
filtering of large genomic data sets that is flexible in the use of compute as
well as storage resources. The data resulting from the filter is assumed to be
greatly reduced in size, and can easily be downloaded or routed into e.g. a
Hadoop cluster for subsequent interactive analysis using Hive, Spark or similar
tools. In this respect, our framework also suggests a general model for making
very large datasets of high scientific value more accessible by offering the
possibility for organizations to share the cost of hosting data on hot storage,
without compromising the scalability of downstream analysis.
PMID- 29940843
TI - Semi-supervised machine learning for automated species identification by collagen
peptide mass fingerprinting.
AB - BACKGROUND: Biomolecular methods for species identification are increasingly
being utilised in the study of changing environments, both at the microscopic and
macroscopic levels. High-throughput peptide mass fingerprinting has been largely
applied to bacterial identification, but increasingly used to identify
archaeological and palaeontological skeletal material to yield information on
past environments and human-animal interaction. However, as applications move
away from predominantly domesticate and the more abundant wild fauna to a much
wider range of less common taxa that do not yet have genetically-derived sequence
information, robust methods of species identification and biomarker selection
need to be determined. RESULTS: Here we developed a supervised machine learning
algorithm for classifying the species of ancient remains based on collagen
fingerprinting. The aim was to minimise requirements on prior knowledge of known
species while yielding satisfactory sensitivity and specificity. The algorithm
uses iterations of a modified random forest classifier with a similarity scoring
system to expand its identified samples. We tested it on a set of 6805 spectra
and found that a high level of accuracy can be achieved with a training set of
five identified specimens per taxon. CONCLUSIONS: This method consistently
achieves higher accuracy than two-dimensional principal component analysis and
similar accuracy with hierarchical clustering using optimised parameters, which
greatly reduces requirements for human input. Within the vertebrata, we
demonstrate that this method was able to achieve the taxonomic resolution of
family or sub-family level whereas the genus- or species-level identification may
require manual interpretation or further experiments. In addition, it also
identifies additional species biomarkers than those previously published.
PMID- 29940844
TI - Isolation of quercetin and mandelic acid from Aesculus indica fruit and their
biological activities.
AB - BACKGROUND: In this study Aesculus indica fruit was subjected to isolation of
phytochemicals. Two antioxidants quercetin and Mandelic acid were isolated in
pure state. The free radical scavenging and acetyl choline esterase inhibitory
potential of the crude extract and sub fractions were also determined. RESULTS:
The antioxidant capacity of crude extract, fractions and isolated compounds were
determined by DPPH and ABTS methods. Folin-Ciocalteu reagent method was used to
estimate the total phenolic contents and were found to be 78.34 +/- 0.96, 44.16
+/- 1.05, 65.45 +/- 1.29, 37.85 +/- 1.44 and 50.23 +/- 2.431 (mg/g of gallic
acid) in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fractions
respectively. The flavonoid concentration in crude extract, ethyl acetate,
chloroform, n-hexane and aqueous fraction were; 85.30 +/- 1.20, 53.80 +/- 1.07,
77.50 +/- 1.12, 26.30 +/- 1.35 and 37.78 +/- 1.25 (mg/g of quercetin)
respectively. The chloroform fraction was more potent against enzymes, acetyl
choline esterase and butyryl choline esterase (IC50 = 85 and 160 MUg/ml
respectively). The phenolic compounds in the crude extract and fractions were
determined using HPLC standard method. Chlorogenic acid, quercetin,
phloroglucinol, rutin, mandelic acid and hydroxy benzoic acid were detected at
retention times 6.005, 10.062, 22.623, 30.597, 35.490 and 36.211 in crude extract
and different fractions. The ethyl acetate fraction was rich in the targeted
compounds and was therefore subjected to column isolation. The HPLC chromatogram
of isolated compounds showed single peak at specified retention times which
confirms their isolation in pure state. The isolated compounds were then
characterized by FTIR and NMR spectrophotometric techniques. CONCLUSION: The
Aesculus indica fruit extracts showed antioxidant and anticholine esterase
inhibitory potentials. Two bioactive compounds were isolated in the pure form
ethyl acetate fraction. From results it was concluded that the fruit of this
plant could be used to minimize oxidative stress caused by reactive oxygen
species.
PMID- 29940845
TI - A computational approach to identify cellular heterogeneity and tissue-specific
gene regulatory networks.
AB - BACKGROUND: The heterogeneity of cells across tissue types represents a major
challenge for studying biological mechanisms as well as for therapeutic targeting
of distinct tissues. Computational prediction of tissue-specific gene regulatory
networks may provide important insights into the mechanisms underlying the
cellular heterogeneity of cells in distinct organs and tissues. RESULTS: Using
three pathway analysis techniques, gene set enrichment analysis (GSEA),
parametric analysis of gene set enrichment (PGSEA), alongside our novel model
(HeteroPath), which assesses heterogeneously upregulated and downregulated genes
within the context of pathways, we generated distinct tissue-specific gene
regulatory networks. We analyzed gene expression data derived from freshly
isolated heart, brain, and lung endothelial cells and populations of neurons in
the hippocampus, cingulate cortex, and amygdala. In both datasets, we found that
HeteroPath segregated the distinct cellular populations by identifying regulatory
pathways that were not identified by GSEA or PGSEA. Using simulated datasets,
HeteroPath demonstrated robustness that was comparable to what was seen using
existing gene set enrichment methods. Furthermore, we generated tissue-specific
gene regulatory networks involved in vascular heterogeneity and neuronal
heterogeneity by performing motif enrichment of the heterogeneous genes
identified by HeteroPath and linking the enriched motifs to regulatory
transcription factors in the ENCODE database. CONCLUSIONS: HeteroPath assesses
contextual bidirectional gene expression within pathways and thus allows for
transcriptomic assessment of cellular heterogeneity. Unraveling tissue-specific
heterogeneity of gene expression can lead to a better understanding of the
molecular underpinnings of tissue-specific phenotypes.
PMID- 29940846
TI - SNPrune: an efficient algorithm to prune large SNP array and sequence datasets
based on high linkage disequilibrium.
AB - BACKGROUND: High levels of pairwise linkage disequilibrium (LD) in single
nucleotide polymorphism (SNP) array or whole-genome sequence data may affect both
performance and efficiency of genomic prediction models. Thus, this warrants
pruning of genotyping data for high LD. We developed an algorithm, named SNPrune,
which enables the rapid detection of any pair of SNPs in complete or high LD
throughout the genome. METHODS: LD, measured as the squared correlation between
phased alleles (r2), can only reach a value of 1 when both loci have the same
count of the minor allele. Sorting loci based on the minor allele count, followed
by comparison of their alleles, enables rapid detection of loci in complete LD.
Detection of loci in high LD can be optimized by computing the range of the minor
allele count at another locus for each possible value of the minor allele count
that can yield LD values higher than a predefined threshold. This efficiently
reduces the number of pairs of loci for which LD needs to be computed, instead of
considering all pairwise combinations of loci. The implemented algorithm SNPrune
considered bi-allelic loci either using phased alleles or allele counts as input.
SNPrune was validated against PLINK on two datasets, using an r2 threshold of
0.99. The first dataset contained 52k SNP genotypes on 3534 pigs and the second
dataset contained simulated whole-genome sequence data with 10.8 million SNPs and
2500 animals. RESULTS: SNPrune removed a similar number of SNPs as PLINK from the
pig data but SNPrune was almost 12 times faster than PLINK. From the simulated
sequence data with 10.8 million SNPs, SNPrune removed 6.4 and 1.4 million SNPs
due to complete and high LD. Results were very similar regardless of whether
phased alleles or allele counts were used. Using allele counts and multi
threading with 10 threads, SNPrune completed the analysis in 21 min. Using a
sliding window of up to 500,000 SNPs, PLINK removed ~ 43,000 less SNPs (0.6%) in
the sequence data and SNPrune was 24 to 170 times faster, using one or ten
threads, respectively. CONCLUSIONS: The SNPrune algorithm developed here is able
to remove SNPs in high LD throughout the genome very efficiently in large
datasets.
PMID- 29940847
TI - ToTem: a tool for variant calling pipeline optimization.
AB - BACKGROUND: High-throughput bioinformatics analyses of next generation sequencing
(NGS) data often require challenging pipeline optimization. The key problem is
choosing appropriate tools and selecting the best parameters for optimal
precision and recall. RESULTS: Here we introduce ToTem, a tool for automated
pipeline optimization. ToTem is a stand-alone web application with a
comprehensive graphical user interface (GUI). ToTem is written in Java and PHP
with an underlying connection to a MySQL database. Its primary role is to
automatically generate, execute and benchmark different variant calling pipeline
settings. Our tool allows an analysis to be started from any level of the process
and with the possibility of plugging almost any tool or code. To prevent an over
fitting of pipeline parameters, ToTem ensures the reproducibility of these by
using cross validation techniques that penalize the final precision, recall and F
measure. The results are interpreted as interactive graphs and tables allowing an
optimal pipeline to be selected, based on the user's priorities. Using ToTem, we
were able to optimize somatic variant calling from ultra-deep targeted gene
sequencing (TGS) data and germline variant detection in whole genome sequencing
(WGS) data. CONCLUSIONS: ToTem is a tool for automated pipeline optimization
which is freely available as a web application at https://totem.software .
PMID- 29940848
TI - Conservation status and historical relatedness of Italian cattle breeds.
AB - BACKGROUND: In the last 50 years, the diversity of cattle breeds has experienced
a severe contraction. However, in spite of the growing diffusion of cosmopolite
specialized breeds, several local cattle breeds are still farmed in Italy.
Genetic characterization of breeds represents an essential step to guide
decisions in the management of farm animal genetic resources. The aim of this
work was to provide a high-resolution representation of the genome-wide diversity
and population structure of Italian local cattle breeds using a medium-density
single nucleotide polymorphism (SNP) array. RESULTS: After quality control
filtering, the dataset included 31,013 SNPs for 800 samples from 32 breeds. Our
results on the genetic diversity of these breeds agree largely with their
recorded history. We observed a low level of genetic diversity, which together
with the small size of the effective populations, confirmed that several breeds
are threatened with extinction. According to the analysis of runs of
homozygosity, evidence of recent inbreeding was strong in some local breeds, such
as Garfagnina, Mucca Pisana and Pontremolese. Patterns of genetic
differentiation, shared ancestry, admixture events, and the phylogenetic tree,
all suggest the presence of gene flow, in particular among breeds that originate
from the same geographical area, such as the Sicilian breeds. In spite of the
complex admixture events that most Italian cattle breeds have experienced, they
have preserved distinctive characteristics and can be clearly discriminated,
which is probably due to differences in genetic origin, environment, genetic
isolation and inbreeding. CONCLUSIONS: This study is the first exhaustive genome
wide analysis of the diversity of Italian cattle breeds. The results are of
significant importance because they will help design and implement conservation
strategies. Indeed, efforts to maintain genetic diversity in these breeds are
needed. Improvement of systems to record and monitor inbreeding in these breeds
may contribute to their in situ conservation and, in view of this, the
availability of genomic data is a fundamental resource.
PMID- 29940849
TI - Genome data uncover four synergistic key regulators for extremely small body size
in horses.
AB - BACKGROUND: Miniature size in horses represents an extreme reduction of withers
height that originated after domestication. In some breeds, it is a highly
desired trait representing a breed- or subtype-specific feature. The genomic
changes that emerged due to strong-targeted selection towards this distinct type
remain unclear. RESULTS: Comparisons of whole-genome sequencing data from two
Miniature Shetland ponies and one standard-sized Shetland pony, performed to
elucidate genetic determinants for miniature size, revealed four synergistic
variants, limiting withers height to 34.25 in. (87 cm). Runs of homozygosity
regions were detected spanning these four variants in both the Miniature Shetland
ponies and the standard-sized Shetland pony. They were shown to be characteristic
of the Shetland pony breed, resulting in a miniature type under specific
genotypic combinations. These four genetic variants explained 72% of the size
variation among Shetland ponies and related breeds. The length of the homozygous
regions indicate that they arose over 1000 years ago. In addition, a copy number
variant was identified in DIAPH3 harboring a loss exclusively in ponies and
donkeys and thus representing a potential height-associated variant. CONCLUSION:
This study reveals main drivers for miniature size in horses identified in whole
genome data and thus provides relevant candidate genes for extremely short
stature in mammals.
PMID- 29940850
TI - A missense mutation of plastid RPS4 is associated with chlorophyll deficiency in
Chinese cabbage (Brassica campestris ssp. pekinensis).
AB - BACKGROUND: Plastome mutants are ideal resources for elucidating the functions of
plastid genes. Numerous studies have been conducted for the function of plastid
genes in barley and tobacco; however, related information is limited in Chinese
cabbage. RESULTS: A chlorophyll-deficient mutant of Chinese cabbage that was
derived by ethyl methanesulfonate treatment on isolated microspores showed
uniformly pale green inner leaves and slow growth compared with that shown by the
wild type "Fukuda 50' ('FT'). Genetic analysis revealed that cdm was
cytoplasmically inherited. Physiological and ultrastructural analyses of cdm
showed impaired photosynthesis and abnormal chloroplast development. Utilizing
next generation sequencing, the complete plastomes of cdm and 'FT' were
respectively re-mapped to the reference genome of Chinese cabbage, and an A-to-C
base substitution with a mutation ratio higher than 99% was detected. The
missense mutation of plastid ribosomal protein S4 led to valine substitution for
glycine at residue 193. The expression level of rps4 was analyzed using
quantitative real-time PCR and found lower in than in 'FT'. RNA gel-blot assays
showed that the abundance of mature 23S rRNA, 16S rRNA, 5S rRNA, and 4.5S rRNA
significantly decreased and that the processing of 23S, 16S rRNA, and 4.5S rRNA
was seriously impaired, affecting the ribosomal function in cdm. CONCLUSIONS:
These findings indicated that cdm was a plastome mutant and that chlorophyll
deficiency might be due to an A-to-C base substitution of the plastome-encoded
rps4 that impaired the rRNA processing and affected the ribosomal function.
PMID- 29940851
TI - Genome-wide investigation of WRKY gene family in pineapple: evolution and
expression profiles during development and stress.
AB - BACKGROUND: WRKY proteins comprise a large family of transcription factors that
play important roles in many aspects of physiological processes and adaption to
environment. However, little information was available about the WRKY genes in
pineapple (Ananas comosus), an important tropical fruits. The recent release of
the whole-genome sequence of pineapple allowed us to perform a genome-wide
investigation into the organization and expression profiling of pineapple WRKY
genes. RESULTS: In the present study, 54 pineapple WRKY (AcWRKY) genes were
identified and renamed on the basis of their respective chromosome distribution.
According to their structural and phylogenetic features, the 54 AcWRKYs were
further classified into three main groups with several subgroups. The segmental
duplication events played a major role in the expansion of pineapple WRKY gene
family. Synteny analysis and phylogenetic comparison of group III WRKY genes
provided deep insight into the evolutionary characteristics of pineapple WRKY
genes. Expression profiles derived from transcriptome data and real-time
quantitative PCR analysis exhibited distinct expression patterns of AcWRKY genes
in various tissues and in response to different abiotic stress and hormonal
treatments. CONCLUSIONS: Fifty four WRKY genes were identified in pineapple and
the structure of their encoded proteins, their evolutionary characteristics and
expression patterns were examined in this study. This systematic analysis
provided a foundation for further functional characterization of WRKY genes with
an aim of pineapple crop improvement.
PMID- 29940852
TI - MCSF drives regulatory DC development in stromal co-cultures supporting
hematopoiesis.
AB - BACKGROUND: Splenic stroma overlaid with hematopoietic progenitors supports in
vitro hematopoiesis with production of dendritic-like cells. Co-cultures of
murine lineage-depleted bone marrow over the 5G3 stromal line produce two
populations of cells, characterised as CD11b+CD11c+MHC-II- dendritic-like 'L-DC',
and CD11b+CD11c+MHC-II+ cells, resembling conventional dendritic cells (cDC). To
date, the functional capacity of these two subsets has not been clearly
distinguished. RESULTS: Here we show both the L-DC and cDC-like subsets can be
activated and induce proliferation of OT-I CD8+ T cells, being strong inducers of
IL-2 and IFN-gamma production. Both subsets lack ability to induce proliferation
of OT-II CD4+ T cells. The cDC-like population is shown here to resemble
regulatory DC in that they induce FoxP3 expression and IL-10 production in OT-II
CD4+ T cells, in line with their function as regulatory DC. L-DC did not activate
or induce the proliferation of CD4+ T cells and did not induce FoxP3 expression
in CD4+ T cells. L-DC can be distinguished from cDC-like cells through their
superior endocytic capacity and expression of 4-1BBL, F4/80 and Sirp-alpha. A
comparison of gene expression by the two subsets was consistent with L-DC having
an activated or immunostimulatory DC phenotype, while cDC-like cells reflect
myeloid dendritic cells with inflammatory and suppressive properties, also
consistent with functional characteristics as regulatory DC. When a Transwell
membrane was used to prevent hematopoietic cell contact with stroma, only cDC
like cells and not L-DC were produced, and cell production was dependent on M-CSF
production by stroma. CONCLUSION: Co-cultures of hematopoietic progenitors over
splenic stroma produce two distinct subsets of dendritic-like cells. These are
here distinguished phenotypically and through gene expression differences. While
both resemble DC, there are functionally distinct. L-DC activate CD8+ but not
CD4+ T cells, while the cDC-like population induce regulatory T cells, so
reflecting regulatory DC. The latter can be enriched through Transwell co
cultures with cell production dependent on M-CSF.
PMID- 29940853
TI - Mapping QTLs for water-use efficiency reveals the potential candidate genes
involved in regulating the trait in apple under drought stress.
AB - BACKGROUND: Improvement of water-use efficiency (WUE) can effectively reduce
production losses caused by drought stress. A better understanding of the genetic
determination of WUE in crops under drought stress has great potential value for
developing cultivars adapted to arid regions. To identify the genetic loci
associated with WUE and reveal genes responsible for the trait in apple, we aim
to map the quantitative trait loci (QTLs) for carbon isotope composition, the
proxy for WUE, applying two contrasting irrigating regimes over the two-year
experiment and search for the candidate genes encompassed in the mapped QTLs.
RESULTS: We constructed a high-density genetic linkage map with 10,172 markers of
apple, using single nucleotide polymorphism (SNP) markers obtained through
restriction site-associated DNA sequencing (RADseq) and a final segregating
population of 350 seedlings from the cross of Honeycrisp and Qinguan. In total,
33 QTLs were identified for carbon isotope composition in apple under both well
watered and drought-stressed conditions. Three QTLs were stable over 2 years
under drought stress on linkage groups LG8, LG15 and LG16, as validated by
Kompetitive Allele-Specific PCR (KASP) assays. In those validated QTLs, 258 genes
were screened according to their Gene Ontology functional annotations. Among
them, 28 genes were identified, which exhibited significant responses to drought
stress in 'Honeycrisp' and/or 'Qinguan'. These genes are involved in signaling,
photosynthesis, response to stresses, carbohydrate metabolism, protein metabolism
and modification, hormone metabolism and transport, transport, respiration,
transcriptional regulation, and development regulation. They, especially those
for photoprotection and relevant signal transduction, are potential candidate
genes connected with WUE regulation in drought-stressed apple. CONCLUSIONS: We
detected three stable QTLs for carbon isotope composition in apple under drought
stress over 2 years, and validated them by KASP assay. Twenty-eight candidate
genes encompassed in these QTLs were identified. These stable genetic loci and
series of genes provided here serve as a foundation for further studies on marker
assisted selection of high WUE and regulatory mechanism of WUE in apple exposed
to drought conditions, respectively.
PMID- 29940854
TI - Rapid loss of early antigen-presenting activity of lymph node dendritic cells
against Ag85A protein following Mycobacterium bovis BCG infection.
AB - BACKGROUND: Control of Mycobacterium tuberculosis (Mtb) infection requires CD4+ T
cell responses and major histocompatibility complex class II (MHC II)
presentation of Mtb antigens (Ags). Dendritic cells (DCs) are the most potent of
the Ag-presenting cells and are central to the initiation of T-cell immune
responses. Much research has indicated that DCs play an important role in anti
mycobacterial immune responses at early infection time points, but the kinetics
of Ag presentation by these cells during these events are incompletely
understood. RESULTS: In the present study, we evaluated in vivo dynamics of early
Ag presentation by murine lymph-node (LN) DCs in response to Mycobacterium bovis
bacillus Calmette-Guerin (BCG) Ag85A protein. Results showed that the early Ag
presenting activity of murine DCs induced by M. bovis BCG Ag85A protein in vivo
was transient, appearing at 4 h and being barely detectable at 72 h. The
transcription levels of CIITA, MHC II and the expression of MHC II molecule on
the cell surface increased following BCG infection. Moreover, BCG was found to
survive within the inguinal LN DC pool, representing a continuing source of
mycobacterial Ag85A protein, with which LN DCs formed Ag85A peptide-MHCII
complexes in vivo. CONCLUSIONS: Our results demonstrate that a decrease in Ag85A
peptide production as a result of the inhibition of Ag processing to is largely
responsible for the short duration of Ag presentation by LN DCs during BCG
infection in vivo.
PMID- 29940855
TI - Comparative analysis of binding patterns of MADS-domain proteins in Arabidopsis
thaliana.
AB - BACKGROUND: Correct flower formation requires highly specific temporal and
spatial regulation of gene expression. In Arabidopsis thaliana the majority of
the master regulators that determine flower organ identity belong to the MADS
domain transcription factor family. The canonical DNA binding motif for this
transcription factor family is the CArG-box, which has the consensus CC(A/T)6GG.
However, so far, a comprehensive analysis of MADS-domain binding patterns has not
yet been performed. RESULTS: Eight publicly available ChIP-seq datasets of MADS
domain proteins that regulate the floral transition and flower formation were
analyzed. Surprisingly, the preferred DNA binding motif of each protein was a
CArG-box with an NAA extension. Furthermore, motifs of other transcription
factors were found in the vicinity of binding sites of MADS-domain transcription
factors, suggesting that interaction of MADS-domain proteins with other
transcription factors is important for target gene regulation. Finally,
conservation of CArG-boxes between Arabidopsis ecotypes was assessed to obtain
information about their evolutionary importance. CArG-boxes that fully matched
the consensus were more conserved than other CArG-boxes, suggesting that the
perfect CArG-box is evolutionary more important than other CArG-box variants.
CONCLUSION: Our analysis provides detailed insight into MADS-domain protein
binding patterns. The results underline the importance of an extended version of
the CArG-box and provide a first view on evolutionary conservation of MADS-domain
protein binding sites in Arabidopsis ecotypes.
PMID- 29940856
TI - Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant
liver failure in mice.
AB - BACKGROUND: Potassium channel tetramerisation domain containing 9 (KCTD9), a
member of KCTD family with a DNA-like pentapeptide repeat domain, was found to be
increased particularly in NK cells of patients with HBV-induced acute-on-chronic
liver failure (HBV-ACLF) and experimental viral fulminant hepatitis. Knockdown of
KCTD9 in immortalized NK cells inhibits cytokines production and cytotoxicity. As
NK cell activation was shown to exacerbate liver damage in viral fulminant
hepatitis, we propose that target inhibition of KCTD9 may prohibit NK cells
activity and thus ameliorate liver damage in viral fulminant hepatitis. RESULT:
Hydrodynamic delivery of plasmid expressing short-hairpin RNA against KCTD9
resulted in impaired NK cells function as demonstrated by reduced cytokine
production and cytotoxicity, and ameliorated liver injury as manifested by
improved liver histology and survival rate. In contrast, delivery of plasmid
expressing KCTD9 led to deteriorated disease progression. CONCLUSION:
Interference with KCTD9 expression exert beneficial effect in viral fulminant
hepatitis therapy. Such effect may be mediated by impairment of NK cell
activation.
PMID- 29940857
TI - Late administration of high-frequency electrical stimulation increases nerve
regeneration without aggravating neuropathic pain in a nerve crush injury.
AB - BACKGROUND: High-frequency transcutaneous neuromuscular electrical nerve
stimulation (TENS) is currently used for the administration of electrical current
in denervated muscle to alleviate muscle atrophy and enhance motor function;
however, the time window (i.e. either immediate or delayed) for achieving benefit
is still undetermined. In this study, we conducted an intervention of sciatic
nerve crush injury using high-frequency TENS at different time points to assess
the effect of motor and sensory functional recovery. RESULTS: Animals with left
sciatic nerve crush injury received TENS treatment starting immediately after
injury or 1 week later at a high frequency(100 Hz) or at a low frequency (2 Hz)
as a control. In SFI gait analysis, either immediate or late admission of high
frequency electrical stimulation exerted significant improvement compared to
either immediate or late administration of low-frequency electrical stimulation.
In an assessment of allodynia, immediate high frequency electrical stimulation
caused a significantly decreased pain threshold compared to late high-frequency
or low-frequency stimulation at immediate or late time points.
Immunohistochemistry staining and western blot analysis of S-100 and NF-200
demonstrated that both immediate and late high frequency electrical stimulation
showed a similar effect; however the effect was superior to that achieved with
low frequency stimulation. Immediate high frequency electrical stimulation
resulted in significant expression of TNF-alpha and synaptophysin in the dorsal
root ganglion, somatosensory cortex, and hippocampus compared to late electrical
stimulation, and this trend paralleled the observed effect on somatosensory
evoked potential. The CatWalk gait analysis also showed that immediate electrical
stimulation led to a significantly high regularity index. In primary dorsal root
ganglion cells culture, high-frequency electrical stimulation also exerted a
significant increase in expression of TNF-alpha, synaptophysin, and NGF in
accordance with the in vivo results. CONCLUSION: Immediate or late transcutaneous
high-frequency electrical stimulation exhibited the potential to stimulate the
motor nerve regeneration. However, immediate electrical stimulation had a
predilection to develop neuropathic pain. A delay in TENS initiation appears to
be a reasonable approach for nerve repair and provides the appropriate time
profile for its clinical application.
PMID- 29940858
TI - Multivariate genome-wide association analysis identifies novel and relevant
variants associated with anterior cruciate ligament rupture risk in the dog
model.
AB - BACKGROUND: Anterior cruciate ligament rupture (ACLR) is a debilitating and
potentially life-changing condition in humans, as there is a high prevalence of
early-onset osteoarthritis after injury. Identification of high-risk individuals
before they become patients is important, as post-treatment lifetime burden of
ACLR in the USA ranges from $7.6 to $17.7 billion annually. ACLR is a complex
disease with multiple risk factors including genetic predisposition. Naturally
occurring ACLR in the dog is an excellent model for human ACLR, as risk factors
and disease characteristics in humans and dogs are similar. In a univariate
genome-wide association study (GWAS) of 237 Labrador Retrievers, we identified 99
ACLR candidate loci. It is likely that additional variants remain to be
identified. Joint analysis of multiple correlated phenotypes is an underutilized
technique that increases statistical power, even when only one phenotype is
associated with the trait. Proximal tibial morphology has been shown to affect
ACLR risk in both humans and dogs. In the present study, tibial plateau angle
(TPA) and relative tibial tuberosity width (rTTW) were measured on bilateral
radiographs from purebred Labrador Retrievers that were recruited to our initial
GWAS. We performed a multivariate genome wide association analysis of ACLR
status, TPA, and rTTW. RESULTS: Our analysis identified 3 loci with moderate
evidence of association that were not previously associated with ACLR. A locus on
Chr1 associated with both ACLR and rTTW is located within ROR2, a gene important
for cartilage and bone development. A locus on Chr4 associated with both ACLR and
TPA resides within DOCK2, a gene that has been shown to promote immune cell
migration and invasion in synovitis, an important predictor of ACLR. A third
locus on Chr23 associated with only ACLR is located near a long non-coding RNA
(lncRNA). LncRNA's are important for regulation of gene transcription and
translation. CONCLUSIONS: These results did not overlap with our previous GWAS,
which is reflective of the different methods used, and supports the need for
further work. The results of the present study are highly relevant to ACLR
pathogenesis, and identify potential drug targets for medical treatment.
PMID- 29940859
TI - A biolistic method for high-throughput production of transgenic wheat plants with
single gene insertions.
AB - BACKGROUND: The relatively low efficiency of biolistic transformation and
subsequent integration of multiple copies of the introduced gene/s significantly
complicate the genetic modification of wheat (Triticum aestivum) and other plant
species. One of the key factors contributing to the reproducibility of this
method is the uniformity of the DNA/gold suspension, which is dependent on the
coating procedure employed. It was also shown recently that the relative
frequency of single copy transgene inserts could be increased through the use of
nanogram quantities of the DNA during coating. RESULTS: A simplified DNA/gold
coating method was developed to produce fertile transgenic plants, via
microprojectile bombardment of callus cultures induced from immature embryos. In
this method, polyethyleneglycol (PEG) and magnesium salt solutions were utilized
in place of the spermidine and calcium chloride of the standard coating method,
to precipitate the DNA onto gold microparticles. The prepared microparticles were
used to generate transgenics from callus cultures of commercial bread wheat cv.
Gladius resulting in an average transformation frequency of 9.9%. To increase the
occurrence of low transgene copy number events, nanogram amounts of the minimal
expression cassettes containing the gene of interest and the hpt gene were used
for co-transformation. A total of 1538 transgenic wheat events were generated
from 15,496 embryos across 19 independent experiments. The variation of single
copy insert frequencies ranged from 16.1 to 73.5% in the transgenic wheat plants,
which compares favourably to published results. CONCLUSIONS: The DNA/gold coating
procedure presented here allows efficient, large scale transformation of wheat.
The use of nanogram amounts of vector DNA improves the frequency of single copy
transgene inserts in transgenic wheat plants.
PMID- 29940860
TI - The arrhythmogenic cardiomyopathy-specific coding and non-coding transcriptome in
human cardiac stromal cells.
AB - BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a genetic autosomal disease
characterized by abnormal cell-cell adhesion, cardiomyocyte death, progressive
fibro-adipose replacement of the myocardium, arrhythmias and sudden death.
Several different cell types contribute to the pathogenesis of ACM, including, as
recently described, cardiac stromal cells (CStCs). In the present study, we aim
to identify ACM-specific expression profiles of human CStCs derived from
endomyocardial biopsies of ACM patients and healthy individuals employing TaqMan
Low Density Arrays for miRNA expression profiling, and high throughput sequencing
for gene expression quantification. RESULTS: We identified 3 miRNAs and 272 genes
as significantly differentially expressed at a 5% false discovery rate. Both the
differentially expressed genes as well as the target genes of the ACM-specific
miRNAs were found to be enriched in cell adhesion-related biological processes.
Functional similarity and protein interaction-based network analyses performed on
the identified deregulated genes, miRNA targets and known ACM-causative genes
revealed clusters of highly related genes involved in cell adhesion,
extracellular matrix organization, lipid transport and ephrin receptor signaling.
CONCLUSIONS: We determined for the first time the coding and non-coding
transcriptome characteristic of ACM cardiac stromal cells, finding evidence for a
potential contribution of miRNAs, specifically miR-29b-3p, to ACM pathogenesis or
phenotype maintenance.
PMID- 29940861
TI - A high-density genetic map of extra-long staple cotton (Gossypium barbadense)
constructed using genotyping-by-sequencing based single nucleotide polymorphic
markers and identification of fiber traits-related QTL in a recombinant inbred
line population.
AB - BACKGROUND: Gossypium barbadense (Sea Island, Egyptian or Pima cotton) cotton has
high fiber quality, however, few studies have investigated the genetic basis of
its traits using molecular markers. Genome complexity reduction approaches such
as genotyping-by-sequencing have been utilized to develop abundant markers for
the construction of high-density genetic maps to locate quantitative trait loci
(QTLs). RESULTS: The Chinese G. barbadense cultivar 5917 and American Pima S-7
were used to develop a recombinant inbred line (RIL) population with 143 lines.
The 143 RILs together with their parents were tested in three replicated field
tests for lint yield traits (boll weight and lint percentage) and fiber quality
traits (fiber length, fiber elongation, fiber strength, fiber uniformity and
micronaire) and then genotyped using GBS to develop single-nucleotide
polymorphism (SNP) markers. A high-density genetic map with 26 linkage groups
(LGs) was constructed using 3557 GBS SNPs spanning a total genetic distance of
3076.23 cM at an average density of 1.09 cM between adjacent markers. A total of
42 QTLs were identified, including 24 QTLs on 12 LGs for fiber quality and 18
QTLs on 7 LGs for lint yield traits, with LG1 (9 QTLs), LG10 (7 QTLs) and LG14 (6
QTLs) carrying more QTLs. Common QTLs for the same traits and overlapping QTLs
for different traits were detected. Each individual QTLs explained 0.97 to 20.7%
of the phenotypic variation. CONCLUSIONS: This study represents one of the first
genetic mapping studies on the fiber quality and lint yield traits in a RIL
population of G. barbadense using GBS-SNPs. The results provide important
information for the subsequent fine mapping of QTLs and the prediction of
candidate genes towards map-based cloning and marker-assisted selection in
cotton.
PMID- 29940862
TI - A correction for sample overlap in genome-wide association studies in a polygenic
pleiotropy-informed framework.
AB - BACKGROUND: There is considerable evidence that many complex traits have a
partially shared genetic basis, termed pleiotropy. It is therefore useful to
consider integrating genome-wide association study (GWAS) data across several
traits, usually at the summary statistic level. A major practical challenge
arises when these GWAS have overlapping subjects. This is particularly an issue
when estimating pleiotropy using methods that condition the significance of one
trait on the signficance of a second, such as the covariate-modulated false
discovery rate (cmfdr). RESULTS: We propose a method for correcting for sample
overlap at the summary statistic level. We quantify the expected amount of
spurious correlation between the summary statistics from two GWAS due to sample
overlap, and use this estimated correlation in a simple linear correction that
adjusts the joint distribution of test statistics from the two GWAS. The
correction is appropriate for GWAS with case-control or quantitative outcomes.
Our simulations and data example show that without correcting for sample overlap,
the cmfdr is not properly controlled, leading to an excessive number of false
discoveries and an excessive false discovery proportion. Our correction for
sample overlap is effective in that it restores proper control of the false
discovery rate, at very little loss in power. CONCLUSIONS: With our proposed
correction, it is possible to integrate GWAS summary statistics with overlapping
samples in a statistical framework that is dependent on the joint distribution of
the two GWAS.
PMID- 29940864
TI - Can coffee or chewing gum decrease transit times in Colon capsule endoscopy? A
randomized controlled trial.
AB - BACKGROUND: A high rate of complete colon capsule endoscopy (CCE) investigations
is required for a more widespread use of CCE. The objective of this study was to
assess if coffee or chewing gum can increase excretion of the colon capsule
within battery life time (excretion rate). METHODS: One hundred eighty six
screening participants with a positive immunochemical fecal occult blood test
were included in this single-centre randomized controlled trial with blinding of
the investigators to the randomization. Participants received instant coffee,
chewing gum or nothing in addition to the standard bowel preparation. RESULTS:
The intention was to include 57 participants in the coffee group, 61 in the
chewing gum group and 60 in the control group, on 8 participants data were
missing. A total of 165 participants were included in a per protocol analysis.
Exclusion was due to not receiving the allocated intervention (8 coffee, 4
chewing gum) and technical failure of the capsule (1 coffee). The excretion rate
was 58% in the coffee group (n = 48), 63% in the chewing gum group (n = 57) and
55% in the control group (n = 60, p > 0.2). Transit times were similar in all
groups. The excretion rate was low in participants who had transit times over 10
h (14%). A strong correlation was found between adequate cleansing and excretion
of the capsule. There were no serious adverse events related to the interventions
or CCE investigations. CONCLUSIONS: Chewing gum and coffee did not improve
excretion rate in this study. An effect of chewing gum could not be proven,
possibly due to sample size. Since chewing gum might improve excretion rates, is
cheap and has no known side effects, it needs to be considered in future bowel
preparation trials for CCE. TRIAL REGISTRATION: NCT02303756 , registered on
December 1st 2014.
PMID- 29940863
TI - COP9 signalosome subunit 5A affects phenylpropanoid metabolism, trichome
formation and transcription of key genes of a regulatory tri-protein complex in
Arabidopsis.
AB - BACKGROUND: Trichomes and phenylpropanoid-derived phenolics are structural and
chemical protection against many adverse conditions. Their production is
regulated by a network that includes a TTG1/bHLH/MYB tri-protein complex in
Arabidopsis. CSN5a, encoding COP9 signalosome subunit 5a, has also been
implicated in trichome and anthocyanin production; however, the regulatory roles
of CSN5a in the processes through interaction with the tri-protein complex has
yet to be investigated. RESULTS: In this study, a new csn5a mutant, sk372, was
recovered based on its altered morphological and chemical phenotypes compared to
wild-type control. Mutant characterization was conducted with an emphasis on
trichome and phenylpropanoid production and possible involvement of the tri
protein complex using metabolite and gene transcription profiling and scanning
electron microscopy. Seed metabolite analysis revealed that defective CSN5a led
to an enhanced production of many compounds in addition to anthocyanin, most
notably phenylpropanoids and carotenoids as well as a glycoside of zeatin.
Consistent changes in carotenoids and anthocyanin were also found in the sk372
leaves. In addition, 370 genes were differentially expressed in 10-day old
seedlings of sk372 compared to its wild type control. Real-time transcript
quantitative analysis showed that in sk372, GL2 and tri-protein complex gene TT2
was significantly suppressed (p < 0.05) while complex genes EGL3 and GL3 slightly
decreased (p > 0.05). Complex genes MYB75, GL1 and flavonoid biosynthetic genes
TT3 and TT18 in sk372 were all significantly enhanced. Overexpression of GL3
driven by cauliflower mosaic virus 35S promotor increased the number of single
pointed trichomes only, no other phenotypic recovery in sk372. CONCLUSIONS: Our
results indicated clearly that COP9 signalosome subunit CSN5a affects trichome
production and the metabolism of a wide range of phenylpropanoid and carotenoid
compounds. Enhanced anthocyanin accumulation and reduced trichome production were
related to the enhanced MYB75 and suppressed GL2 and some other differentially
expressed genes associated with the TTG1/bHLH/MYB complexes.
PMID- 29940865
TI - Auxin analysis using laser microdissected plant tissues sections.
AB - BACKGROUND: Quantitative measurement of actual auxin levels in plant tissue is
complimentary to molecular methods measuring the expression of auxin related
genes. Current analytical methods to quantify auxin have pushed the limit of
detection to where auxin can be routinely quantified at the pictogram (pg) level,
reducing the amount of tissue needed to perform these kinds of studies to amounts
never imagined a few years ago. In parallel, the development of technologies like
laser microdissection microscopy (LMD) has allowed specific cells to be harvested
from discrete tissues without including adjacent cells. This method has gained
popularity in recent years, especially for enabling a higher degree of spatial
resolution in transcriptome profiling. As with other quantitative measurements,
including hormone quantifications, sampling using traditional LMD is still
challenging because sample preparation clearly compromises the preservation of
analytes. Thus, we have developed and validated a sample preparation protocol
combining cryosectioning, freeze-drying, and capturing with a laser
microdissection microscope to provide high-quality and well-preserved plant
materials suitable for ultrasensitive, spatially-resolved auxin quantification.
RESULTS: We developed a new method to provide discrete plant tissues for indole-3
acetic acid (IAA) quantification while preserving the plant tissue in the best
possible condition to prevent auxin degradation. The method combines the use of
cryosectioning, freeze-drying and LMD. The protocol may also be used for other
applications that require small molecule analysis with high tissue-specificity
where degradation of biological compounds may be an issue. It was possible to
collect the equivalent to 15 mg of very specific tissue in approximately 4 h
using LMD. CONCLUSIONS: We have shown, by proof of concept, that freeze dried
cryosections of plant tissue were suitable for LMD harvest and quantification of
the phytohormone auxin using GC-MS/MS. We expect that the ability to resolve
auxin levels with both spatial- and temporal resolution with high accuracy will
enable experiments on complex processes, which will increase our knowledge of the
many roles of auxins (and, in time, other phytohormones) in plant development.
PMID- 29940866
TI - Evaluation of surrogate measures of insulin sensitivity - correlation with gold
standard is not enough.
AB - BACKGROUND: Impaired insulin sensitivity is a key abnormality underlying the
development of type 2 diabetes. Measuring insulin sensitivity is therefore of
importance in identifying individuals at risk of developing diabetes and for the
evaluation of diabetes-focused interventions. A number of measures have been
proposed for this purpose. Among these the hyperinsulinemic euglycemic clamp
(HEC) is considered the gold standard. However, as the HEC is a costly, time
consuming and invasive method requiring trained staff, there is a need for
simpler so called surrogate measures. MAIN MESSAGE: A frequently used approach to
evaluate surrogate measures is through correlation with the HEC. We discuss
limitations with this method. We suggest other aspects to take into
consideration, such as repeatability, reproducibility, systematic biases and
discrimination ability. In addition, we focus on three frequently used surrogate
measures. We argue that they are one-to-one transformations of each other, and
therefore question the benefits of further comparison between them. They give the
same results in all rank-based methods, for instance Spearman correlations, Mann
Whitney tests and receiver operating characteristic (ROC) analysis. CONCLUSIONS:
We suggest investigating further aspects than correlation alone when evaluating a
surrogate measure of insulin sensitivity. We recommend choosing one of the three
surrogate measures HOMA-IR, QUICKI and FIRI for analysis of a clinical study.
PMID- 29940867
TI - A case series evaluating the impact of Hepatitis C eradication using direct
acting antivirals on primary biliary cholangitis-associated autoimmunity.
AB - BACKGROUND: Chronic Hepatitis C Virus (HCV) infection has been commonly linked to
the development of autoimmunity, in part through activation of B cells. B cells
are also postulated to play a pathogenic role in the autoimmune liver disease
Primary Biliary Cholangitis (PBC). Patients with concurrent PBC and HCV infection
carry an increased risk of more progressive disease, although the mechanism
underlying this effect is poorly understood. Utilizing a case series of patients
with concurrent PBC and HCV, the aim of this study was to evaluate for the
potential impact of HCV eradication upon autoimmunity/autoantibody production.
CASE PRESENTATION: A case series evaluating three patients with co-existing PBC
HCV infection receiving non-interferon based HCV treatments with direct-acting
antivirals (DAA). One of three patient received Ursodeoxycholic acid (UDCA; 13
mg/kg/day) during the treatment period. Sustained virological response (SVR) to
DAA's was assessed using a HCV Quantitative Nucleic Acid Test (Abbott).
Autoantibodies associated with autoimmune liver diseases (including PBC) and
liver biochemistry, were measured before, during and after DAA treatment (Mitogen
Advanced Diagnostics Laboratory, Calgary, Canada). All patients achieved an SVR,
as determined by negative HCV RNA test 12 weeks post-DAA therapy. Titres of anti
mitochondrial antibodies (AMA-M2), anti- branched-chain 2-oxo-acid dehydrogenase
complex and 2-oxo glutarate dehydrogenase complex (anti-3E-BPO), and anti-
tripartite motif-containing protein 21 (TRIM21/Ro52) remained unchanged, despite
successful HCV eradication. Two of the three patients exhibited a transient
decrease in some autoantibody titres during DAA treatment, but these returned to
baseline levels post-DAA therapy. CONCLUSIONS: Within the limitations of a case
series, our results suggest that HCV co-infection may not be a significant driver
of PBC-related autoimmunity/autoantibody production. However, a larger n-value is
required to truly assess for the effect of HCV eradication on autoantibody
production.
PMID- 29940868
TI - Geriatric syndromes, multimorbidity, and disability overlap and increase
healthcare use among older Chinese.
AB - BACKGROUND: Geriatric syndromes, multimorbidity, and disability are prevalent
among ageing population. However, no study empirically examined their additive or
synergistic effect on healthcare use. The present study aims to estimate
overlapping prevalence of geriatric syndromes, multimorbidity, and disability;
and to examine associations of these three conditions with healthcare use.
METHODS: A cross-sectional study was conducted in community-dwelling older adults
aged 60 and above in 12 Hong Kong districts. Pearson's chi-squared test for trend
was performed to examine prevalence of geriatric syndromes, multimorbidity, and
disability across three age groups (60-69, 70-79, and >= 80). Multiple logistic
regression was conducted to explore associations of these three conditions with
three types of healthcare use (hospital admission, general outpatient clinic and
specialist outpatient clinic attendance) respectively. RESULTS: Among 2618
participants, 75.3, 41.8, and 22.5% had geriatric syndromes, multimorbidity, and
disability respectively, and 10.4% had all the three conditions. Prevalence of
the three conditions and their coexistence significantly increased with age (p
for trend < .001). Each condition was independently associated with at least two
out of three types of healthcare use. Interestingly, the associations of
multimorbidity and disability with specialist outpatient clinic attendance were
weakened at older age, while the associations of geriatric syndromes with
hospital admission and specialist outpatient clinic attendance were strengthened.
Furthermore, the odds of all the three types of healthcare use increased with the
number of conditions present (p for trend < .001). CONCLUSIONS: Our findings
support that the three conditions overlap and increase healthcare use. Early
identification, prevention and intervention targeting older adults living with
multiple healthcare needs are necessary.
PMID- 29940869
TI - Biochemical and inflammatory modifications after switching to dual antiretroviral
therapy in HIV-infected patients in Italy: a multicenter retrospective cohort
study from 2007 to 2015.
AB - BACKGROUND: Triple-drug regimens are the gold standard for HIV therapy.
Nucleos(t)ide reverse transcriptase inhibitors (NRTIs) reducing regimens are used
to decrease drugs toxicity, exposure and costs. Aim of our study was to evaluate
trends of biochemical and inflammatory indices in patients switching to dual
therapy (DT). METHODS: We included patients that a) switched to a DT from 2007 to
2015 from a tenofovir/abacavir-based triple regimen b) previously maintained a
triple and c) subsequently a dual regimen for 12 months with virological
suppression. We retrieved data measured at 5 points (at the switch, 6 and 12
months before and after switch). We used platelet-to-lymphocyte ratio (PLR),
neutrophil-to-lymphocyte ratio (NLR) and CD4/CD8 ratio as inflammatory indices.
We assessed temporal trends of viro-immunological, biochemical and inflammatory
parameters. RESULTS: Overall, 364 and 65 patients switched from a tenofovir- and
an abacavir-triple regimen, respectively. In the tenofovir-reducing group,
creatinine clearance and lipids raised after the switch. There was a significant
increase in both CD4+ cells and CD4/CD8. CD8+ cells rose after the switch, while
opposite trend was found for PLR. In the abacavir-reducing group total lipids
showed a decrease during the first 6 months after the switch and then stabilized.
An increase of CD4+ and a decrease of CD8+ cells was observed during the study
period, although not statistically significant. While CD4/CD8 remained stable
after simplification, PLR decreased significantly after 6 months, then returning
to baseline. CD8+ cells increased in the tenofovir-reducing group despite a viro
immunological response. Intriguingly, PLR decreased, maintaining this trend for
12 and 6 months after tenofovir and abacavir interruption respectively.
CONCLUSIONS: Increased PLR has been linked to hypercholesterolemia and metabolic
syndrome, while high CD8+ cells count to increased risk of non-AIDS-related
events regardless of CD4 T-cell recovery and to virological failure. Whether
these findings may have clinical implications, and which role DT plays on the
immune system and on inflammation should be further investigated.
PMID- 29940870
TI - Exploration of 27 plasma immune markers: a cross-sectional comparison of 64 old
psychiatric inpatients having unipolar major depression and 18 non-depressed old
persons.
AB - BACKGROUND: The prevalence of major depression (MD) according to population
studies is the same for old (65 years and older) and younger adults. In contrast,
an elevated proportion of old MD patients are hospitalized compared to younger
adults with MD, indicating a need to expand the characteristics of old inpatients
with MD. To illustrate this point, the association between inflammation and MD in
old psychiatric inpatients is sparsely investigated even though an association
between inflammation and treatment resistance among younger adults with MD has
been reported. In this study, we aimed to explore the plasma concentrations of 27
immune markers in old inpatients with MD, and our purpose was to expand the
understanding of inflammatory mechanisms in these patients. METHODS: Prior to
electroconvulsive treatment of MD, we compared 64 inpatients with unipolar MD
(mean age 75.2 years) and 18 non-depressed controls (mean age 78.0 years).
Symptoms characterizing MD were assessed by the Hamilton Rating Scale of
Depression (HRSD)-17, and the immune markers from peripheral blood plasma were
analysed using multiplex assay technology. For statistical analysis of data, we
used the independent samples median test, independent samples t-test, chi2-test,
receiver operating characteristic curve analyses, stepwise discriminant analysis,
and multivariate linear regression. RESULTS: Twenty-two immune markers
representing pro- and anti-inflammatory, adaptive and trophic signalling had
higher concentrations in the inpatients compared to the controls. Only the four
immune markers IL-1beta, IL-5, IL-10 and IL-15 had concentrations below the lower
detection limit in a considerable portion (above 20%) of the patient cases. A
combination of the concentration in plasma of TNF, vascular endothelial growth
factor (VEGF), IL-1beta, IL-7 and monocyte chemotactic protein (MCP)-1, correctly
classified 98.4% of the depressed patients and 83.3% of the non-depressed
controls. Plasma concentration of TNF and VEGF were associated with the HRSD-17
scores (p = 0.017 and 0.005, respectively). CONCLUSIONS: Our results indicate
that several inflammatory mechanisms may be highly activated in old psychiatric
inpatients with MD, and indicate that immune markers may contribute to a more
comprehensive understanding of MD in old persons. TRIAL REGISTRATION: NCT01559324
ClinicalTrials.gov.
PMID- 29940871
TI - Multiple morphogenic culture systems cause loss of resistance to cassava mosaic
disease.
AB - BACKGROUND: Morphogenic culture systems are central to crop improvement programs
that utilize transgenic and genome editing technologies. We previously reported
that CMD2-type cassava (Manihot esculenta) cultivars lose resistance to cassava
mosaic disease (CMD) when passed through somatic embryogenesis. As a result,
these plants cannot be developed as products for deployment where CMD is endemic
such as sub-Saharan Africa or the Indian sub-continent. RESULT: In order to
increase understanding of this phenomenon, 21 African cassava cultivars were
screened for resistance to CMD after regeneration through somatic embryogenesis.
Fifteen cultivars were shown to retain resistance to CMD through somatic
embryogenesis, confirming that the existing transformation and gene editing
systems can be employed in these genetic backgrounds without compromising
resistance to geminivirus infection. CMD2-type cultivars were also subjected to
plant regeneration via caulogenesis and meristem tip culture, resulting in 25-36%
and 5-10% of regenerated plant lines losing resistance to CMD respectively.
CONCLUSIONS: This study provides clear evidence that multiple morphogenic systems
can result in loss of resistance to CMD, and that somatic embryogenesis per se is
not the underlying cause of this phenomenon. The information described here is
critical for interpreting genomic, transcriptomic and epigenomic datasets aimed
at understanding CMD resistance mechanisms in cassava.
PMID- 29940872
TI - A 73,128 bp de novo deletion encompassing the OPN1LW/OPN1MW gene cluster in
sporadic Blue Cone Monochromacy: a case report.
AB - BACKGROUND: Blue Cone Monochromacy (BCM) is a rare congenital cone dysfunction
disorder with X-linked recessive mode of inheritance. BCM is caused by mutations
at the OPN1LW/MW cone opsin gene cluster including deletions of the locus control
region (LCR) and/or parts of the gene cluster. We aimed at investigating the
clinical presentation, genetic cause and inheritance underlying a sporadic case
of BCM. CASE PRESENTATION: We report a 24-year-old male presenting with
congenital photophobia, nystagmus and colour vision abnormalities. There was no
history of retinal dystrophy in the family. Clinical diagnosis of BCM was
supported by genetic investigations of the patient and his family members.
Molecular genetic analysis of the OPN1LW/OPN1MW gene cluster revealed a novel
deletion of about 73 kb in the patient encompassing the LCR. The deletion was
absent in the X-chromosomes of both the mother and transmitting grandfather.
CONCLUSIONS: The present report provides the clinical findings and the genetic
basis underlying a sporadic BCM case which is caused by a de novo deletion within
the OPN1LW/MW gene cluster originating from the mother's germline due to Alu
repeat mediated recombination. This is the first report of a de novo deletion
resulting in BCM, highlighting the importance to consider BCM and perform genetic
testing for this condition in male patients with cone dysfunction also in the
absence of a positive family history.
PMID- 29940873
TI - How do clients in Australia experience Consumer Directed Care?
AB - BACKGROUND: Our study explored client experience of Australian Consumer Directed
Care. This evolving funding model enables consumer autonomy and choice, allowing
older people to remain in their community as they age and need support through
the creation of a personalised support service. Consumer Directed Care focuses on
providing services that the consumer self-determines to meeting their needs
including identifying their types of services, from whom, when and how these
services are delivered. METHODS: Semi-structured in-depth interviews were
conducted in two Australian states between August 2015 and April 2016 with 14
participants, preferably in receipt of CDC services for at least the previous 12
months. Questions explored how the participant first learned about this service;
the types of services they received; whether services met their needs; and any
additional support services they personally purchased. Interviews were
transcribed, coded and thematically analysed. RESULTS: Four main themes related
to consumer experience emerged. Knowledge: Unsure what Consumer Directed Care
Means. Acceptance: Happily taking any prescriptive service that is offered.
Compliance: Unhappily acceding to the prescriptive service that is offered.
External Influences: Previous aged care service experience, financial position,
and cultural differences. CONCLUSION: Our results suggest that the anticipated
outcomes of Consumer Directed Care providing a better service experience were
limited by existing client knowledge of these services, how best to utilise their
funding allocation, and their acceptance or compliance with what was offered,
even if this was not personalised or sufficient. External influences, such as
service experience, finances, cultural difference, impacted the way clients
managed their allocation. Our study identified that ongoing engagement and
discussion with the client is required to ensure that services are specific,
directly relevant and effective to achieving a consumer directed care service.
PMID- 29940874
TI - Hemoglobin levels during the first trimester of pregnancy are associated with the
risk of gestational diabetes mellitus, pre-eclampsia and preterm birth in Chinese
women: a retrospective study.
AB - BACKGROUND: Hemoglobin (Hb) measurement is a standard test among pregnant women
during the first perinatal visit that is used to evaluate physical status and
anemia. However, studies focusing on Hb levels and pregnancy outcomes are scarce.
This study aimed to determine whether Hb levels in early pregnancy were
associated with the risk of gestational diabetes mellitus (GDM), pre-eclampsia
(PE) and preterm birth. METHODS: A hospital-based retrospective study was
conducted among 21,577 singleton, non-smoking pregnancies between June 2013 and
January 2015. The demographic data and medical information of each participant
were collected individually through questionnaires and patient medical records.
Odds ratios were generated using a multivariate logistic regression analysis to
evaluate the relative risk of GDM, PE and preterm birth continuously and across
different hemoglobin ranges in the overall population and in women from different
pre-pregnancy body mass index (BMI) categories, respectively. The level of
statistical significance was set at 0.05. RESULTS: (1) For women who were
underweight, normal-weight, overweight and obese, early pregnancy Hb levels were
127.8 +/- 10.1 g/L, 129.6 +/- 9.7 g/L, 132.2 +/- 9.5 g/L and 133.4 +/- 9.4 g/L,
respectively. (2) Women with GDM and PE had significantly increased Hb levels
during early pregnancy compared with controls, whereas women with preterm birth
processed significantly decreased Hb levels. (3) After adjusting for confounders,
the risks for GDM and PE increased with high maternal Hb (OR: 1.27 for Hb 130
149; OR: 2.06 for Hb >= 150 g/L), and the risk for preterm birth decreased with
high maternal Hb (OR: 1.30 for Hb 130-149; OR: 2.38 for Hb >= 150 g/L) and
increased with low maternal Hb (OR: 1.41 for Hb < 110 g/L). Among women whose
BMI was < 24 kg/m2, high GDM (OR: 1.27 for Hb 130-149; OR: 1.84 for Hb >= 150
g/L) and low preterm rates (OR: 0.77 for Hb 130-149; OR: 0.23 for Hb >= 150 g/L)
were observed with high Hb, whereas in women whose BMI was >=24 kg/m2, only high
GDM rates were observed with Hb > 150 g/L (OR: 2.33). CONCLUSION: These findings
suggest that Hb levels during early pregnancy play a role in predicting the risk
of GDM, PE and preterm birth.
PMID- 29940875
TI - The study protocol for PREDICT AF RECURRENCE: a PRospEctive cohort stuDy of
surveIllanCe for perioperaTive Atrial Fibrillation RECURRENCE in major non
cardiac surgery for malignancy.
AB - BACKGROUND: A previous retrospective cohort study established the relationship
between perioperative atrial fibrillation (POAF) and subsequent mortality and
stroke. However, the details regarding the cause of death and etiology of stroke
remain unclear. METHODS: The prospective cohort study of surveillance for
perioperative atrial fibrillation recurrence in major non-cardiac surgery for
malignancy (PREDICT AF RECURRENCE) registry is an ongoing prospective cohort
study to elucidate the long-term recurrence rate and the clinical impact of new
onset POAF in the setting of head and neck, non-cardiac thoracic, and abdominal
surgery for malignancy. In this study, cardiologists collaborate with a surgical
team during the perioperative period, carefully observe the electrocardiogram
(ECG) monitor, and treat arrhythmia as required. Furthermore, patients who
develop new-onset POAF are followed up using a long-term Holter ECG monitor,
SPIDER FLASH-t AFib(r), to assess POAF recurrence. DISCUSSION: Even if patients
with malignancy survive by overcoming the disease, they may die from any
preventable cardiovascular diseases. In particular, those with POAF may develop
cardiogenic stroke in the future. Because details of the natural history of
patients with POAF remain unclear, investigating the need to continue
anticoagulation therapy for such patients is necessary. This study will provide
essential information on the recurrence rate of POAF and new insights into the
prediction and treatment of POAF. TRIAL REGISTRATION: University Hospital Medical
Information Network Clinical Trial Registry (UMIN-CTR): UMIN000016146 ; Data of
Registration: January 7, 2015.
PMID- 29940876
TI - The KDIGO acute kidney injury guidelines for cardiac surgery patients in critical
care: a validation study.
AB - BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney
Injury (AKI) guidelines assign the same stage of AKI to patients whether they
fulfil urine output criteria, serum creatinine criteria or both criteria for that
stage. This study explores the validity of the KDIGO guidelines as a tool to
stratify the risk of adverse outcomes in cardiac surgery patients. METHODS:
Prospective data from consecutive adult patients admitted to the cardiac
intensive care unit (CICU) following cardiac surgery between January 2013 and May
2015 were analysed. Patients were assigned to groups based on the criteria they
met for each stage of AKI according to the KDIGO guidelines. Short and mid-term
outcomes were compared between these groups. RESULTS: A total of 2267 patients
were included with 772 meeting criteria for AKI-1 and 222 meeting criteria for
AKI-2. After multivariable adjustment, patients meeting both urine output and
creatinine criteria for AKI-1 were more likely to experience prolonged CICU stay
(OR 4.9, 95%CI 3.3-7.4, p < 0.01) and more likely to require renal replacement
therapy (OR 10.5, 95%CI 5.5-21.9, p < 0.01) than those meeting only the AKI-1
urine output criterion. Patients meeting both urine output and creatinine
criteria for AKI-1 were at an increased risk of mid-term mortality compared to
those diagnosed with AKI-1 by urine output alone (HR 2.8, 95%CI 1.6-4.8, p <
0.01). Patients meeting both urine output and creatinine criteria for AKI-2 were
more likely to experience prolonged CICU stay (OR 16.0, 95%CI 3.2-292.0, p <
0.01) or require RRT (OR 11.0, 95%CI 4.2-30.9, p < 0.01) than those meeting only
the urine output criterion. Patients meeting both urine output and creatinine
criteria for AKI-2 were at a significantly increased risk of mid-term mortality
compared to those diagnosed with AKI-2 by urine output alone (HR 3.6, 95%CI 1.4
9.3, p < 0.01). CONCLUSIONS: Patients diagnosed with the same stage of AKI by
different KDIGO criteria following cardiac surgery have significantly different
short and mid-term outcomes. The KDIGO criteria need to be revisited before they
can be used to stratify reliably the severity of AKI in cardiac surgery patients.
The utility of the criteria also needs to be explored in other settings.
PMID- 29940877
TI - Hematuria as a risk factor for progression of chronic kidney disease and death:
findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.
AB - BACKGROUND: Hematuria is associated with chronic kidney disease (CKD), but has
rarely been examined as a risk factor for CKD progression. We explored whether
individuals with hematuria had worse outcomes compared to those without hematuria
in the CRIC Study. METHODS: Participants were a racially and ethnically diverse
group of adults (21 to 74 years), with moderate CKD. Presence of hematuria
(positive dipstick) from a single urine sample was the primary predictor.
Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and
death, over a median follow-up of 7.3 years, analyzed using Cox Proportional
Hazards models. Net reclassification indices (NRI) and C statistics were
calculated to evaluate their predictive performance. RESULTS: Hematuria was
observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals
with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have
diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and
higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable
adjusted analysis, individuals with hematuria had a greater risk for all outcomes
during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68,
Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2:
1.77), and these associations were attenuated, thereafter. Based on NRIs and C
statistics, no clear improvement in the ability to improve prediction of study
outcomes was observed when hematuria was included in multivariable models.
CONCLUSION: In a large adult cohort with CKD, hematuria was associated with a
significantly higher risk of CKD progression and death in the first 2 years of
follow-up but did not improve risk prediction.
PMID- 29940878
TI - A novel homozygous mutation in the glycerol-3-phosphate dehydrogenase 1 gene in a
Chinese patient with transient infantile hypertriglyceridemia: a case report.
AB - BACKGROUND: Transient infantile hypertriglyceridemia (HTGTI) is an autosomal
recessive disorder caused by mutations in the glycerol-3-phosphate dehydrogenase
1 (GPD1) gene. CASE PRESENTATION: We report a case of HTGTI in a Chinese female
infant. She presented with hepatomegaly, hypertriglyceridemia, moderately
elevated transaminases, and hepatic steatosis at 3.5 months of age. A novel
mutation c.523C>T, p. (Q175*) was identified in GPD1. The patient was a
homozygote and her parents were heterozygous for the mutation. Ultrastructural
study showed intrahepatocytic lipid droplets. CONCLUSIONS: This is the first
reported case of HTGTI in Chinese, expanding the worldwide distribution of HTGTI
and the mutation spectrum of GPD1.
PMID- 29940879
TI - Prevalence of iodine deficiency and associated factors among pregnant women in
Ada district, Oromia region, Ethiopia: a cross- sectional study.
AB - BACKGROUND: Maternal iodine deficiency (ID) during pregnancy has been recognized
as a major cause of abortion, stillbirth, congenital abnormalities, perinatal
mortality and irreversible mental retardation. In Ethiopia limited information is
available regarding the epidemiology of maternal ID. The purpose of the present
study was to assess the prevalence of iodine deficiency and associated factors
among pregnant women in Ada district, Oromia region, Ethiopia. METHOD: A
community based, cross-sectional study was conducted in rural areas of Ada
district, October to November, 2014. Data were collected from 356 pregnant women
selected by multistage cluster sampling technique. Presence of goiter was
examined by palpation and urinary iodine concentration was measured using
inductively-coupled-plasma mass spectrometry. Salt iodine concentration was
determined using a digital electronic iodine checker. Statistical analysis was
done primarily using binary logistic regression. The outputs of the analysis are
presented using adjusted odds ratio (AOR) with the respective 95% confidence
intervals (CI). RESULTS: The median urinary iodine concentration (UIC) was 85.7
(interquartile range (IQR): 45.7-136) MUg/L. Based on UIC, 77.6% (95% CI: 73.0
82.0%) of the study subjects had insufficient iodine intake (UIC < 150 MUg/L).
The goiter rate was 20.2% (95% CI: 16.0-24.0%). The median iodine concentration
of the household salt samples was 12.2 (IQR: 6.9-23.8) ppm. Of the households,
only 39.3% (95% CI: 34.0-44.0%) consumed adequately iodized salt (>=15 ppm).
Prevalence of goiter was significantly higher among pregnant women aged 30-44
years (AOR = 2.32 (95% CI: 1.05-5.14)) than among younger women and among
illiterate women (AOR = 2.71 (95% CI: 1.54-4.79)). Compared to nulliparous, women
with parity of 1, 2 and 3 or more had 2.28 (95% CI: 1.01-5.16), 2.81 (95% CI:
1.17-6.74) and 4.41 (95% CI: 1.58-12.26) times higher risk of goiter. CONCLUSION:
Iodine deficiency was a public health problem in the study area. This indicates
the need for further strengthening of the existing salt iodization program in
order to avail homogenously and adequately iodized salt. Also it is necessary to
find ways to provide iodine supplements as needed until universal salt iodization
(USI) is fully established.
PMID- 29940880
TI - Selection of essential medicines for the prevention and treatment of
cardiovascular diseases in low and middle income countries.
AB - BACKGROUND: The incidence and mortality of cardiovascular diseases (CVDs) in low
and middle income countries (LMICs) have been increasing, while access to CVDs
medicines is suboptimal. We assessed selection of essential medicines for the
prevention and treatment of CVDs on national essential medicines lists (NEMLs) of
LMICs and potential determinants for selection. METHODS: Only operational NEMLs
were considered eligible for this study. A selection of medicines listed under
"cardiovascular medicines" or "blood products and plasma substitutes" in the
NEMLs were included if they were present on international guidelines for the
prevention and treatment of CVDs (hyperlipidemia, hypertension, platelet
inhibition, ischemic stroke, stable ischemic heart disease, acute coronary
syndromes, heart failure, atrial fibrillation, peripheral arterial disease and
acute limb ischemia). The number and diversity of essential medicines selected
for CVDs were studied. Moreover, determinants of selection of essential medicines
for CVDs at a national level were explored. Data analysis was done using
univariate linear regression and non-parametric tests. RESULTS: All medicine
groups listed by the international guidelines were selected by the majority of
the 34 countries studied with the exception of adenosine diphosphate receptor
inhibitors which appeared on less than half of the NEMLs studied (41% of
countries). The total number of essential medicines for the prevention and
treatment of cardiovascular diseases (median 24 (range 16-50)) differed
significantly across income levels (median range: 19.5-25, p = 0.014) and across
regions (median range: 20-32, p = 0.049). When recommendations of the
international guidelines were considered, over 75% of the NEMLs contained
essential medicines for the majority of CVDs. CONCLUSION: The main medicine
classes for the management of CVDs were represented on NEMLs. Consequently, for
the majority of CVDs, evidence-based guideline-recommended treatment is possible
as far as selection of essential medicines is concerned. Selection will therefore
not be the limiting step in access to medicines for cardiovascular diseases.
PMID- 29940881
TI - Admission homocysteine is an independent predictor of spontaneous reperfusion and
early infarct-related artery patency before primary percutaneous coronary
intervention in ST-segment elevation myocardial infarction.
AB - BACKGROUND: Spontaneous reperfusion (SR) and early infarct related artery (IRA)
patency before primary percutaneous coronary intervention (PPCI) might bring
extra benefit for patients with ST-segment elevation myocardial infarction
(STEMI). This study premilinarily screened the independent predictors of SR, and
assessed the relationship between SR and plasma homocysteine (HCY). METHODS: The
medical records of 998 patients who were diagnosed as STEMI and underwent
emergency coronary angiography were retrospectively studied, SR was defined as
achievement of TIMI grade 3 flow in the IRA before PCI. The baseline
characteristics, clinical manifestations and hematological variables were
compared between SR and NSR group. Optimal cutoff point of HCY was calculated
with receiving operating characteristics (ROC) analysis, multivariate logistic
regression models were used to identify predictors of SR. RESULTS: 229 (22.95%)
patients showed angiographic SR. For HCY, the area under the curve was 0.70 (95%
CI: 0.63-0.77, P = 0.034), the optimized cut off point was 17.55 MUmol/L.
Preinfarct angina (95% CI: 1.61-5.65, P = 0.0005), plasma C-reactive protein
(CRP) level (95% CI: 0.87-0.99, P = 0.016) and HCY < 17.55 MUmol/L (95% CI: 2.43
8.72, P < 0.0001) were found to be independent predictors for SR. CONCLUSION: In
patients with STEMI, HCY < 17.55 MUmol/L, preinfarct angina and plasma CRP level
were independent predictors of SR.
PMID- 29940882
TI - Signs and symptoms of disordered eating in pregnancy: a Delphi consensus study.
AB - BACKGROUND: This study aimed to establish consensus on the expression and
distinction of disordered eating in pregnancy to improve awareness across various
health professions and inform the development of a pregnancy-specific assessment
instrument. METHODS: A three-round modified Delphi method was used with two
independent panels. International clinicians and researchers with extensive
knowledge on and/or clinical experience with eating disorders formed the first
panel and were recruited using structured selection criteria. Women who
identified with a lived experience of disordered eating in pregnancy formed the
second panel and were recruited via expressions of interest from study
advertising on pregnancy forums and social media platforms. A systematic search
of academic and grey literature produced 200 sources which were used to pre
populate the Round I questionnaire. Additional items were included in Round II
based on panel feedback in Round I. Consensus was defined as 75% agreement on an
item. RESULTS: Of the 102 items presented to the 26 professional panel members
and 15 consumer panel members, 75 reached consensus across both panels. Both
panels clearly identified signs and symptoms of disordered eating in pregnancy
and endorsed a number of clinical features practitioners should consider when
delineating disordered eating symptomatically from normative pregnancy
experiences. CONCLUSION: A list of signs and symptoms in consensus was
identified. The areas of collective agreement may be used to guide clinicians in
clinical practice, aid the development of psychometric tools to detect/assess
pregnancy-specific disordered eating, in addition to serving as starting point
for the development of a core outcome set to measure disordered eating in
pregnancy.
PMID- 29940883
TI - Coexisting ovarian and tubal pregnancies on opposite sides after intrauterine
insemination: a case report.
AB - BACKGROUND: Ovarian pregnancy is very rare, and contralateral tubal pregnancy
coexisting with ovarian pregnancy must be even rarer. CASE PRESENTATION: A 33
year-old Korean nulliparous woman was referred to our hospital because she
suffered lower abdominal pain and had missed her periods after controlled ovarian
hyperstimulation and intrauterine insemination. We could not identify any normal
gestational sac in the endometrium, or specific ectopic pregnancies, on an
initial ultrasound scan. However, there was a large hematoma in the cul-de-sac
and free fluid in the right paracolic gutter. We decided to perform emergent
laparoscopic surgery. We found contralateral tubal and ovarian ectopic
pregnancies. CONCLUSION: To the best of our knowledge, this is the first report
of a case in which a patient underwent laparoscopic right salpingectomy and left
ovarian ectopic mass excision due to contralateral tubal and ovarian ectopic
pregnancies after assisted reproductive technology.
PMID- 29940884
TI - An inflammation-related nomogram for predicting the survival of patients with non
small cell lung cancer after pulmonary lobectomy.
AB - BACKGROUND: Emerging inflammatory response biomarkers are developed to predict
the survival of patients with cancer, the aim of our study is to establish an
inflammation-related nomogram based on the classical predictive biomarkers to
predict the survivals of patients with non-small cell lung cancer (NSCLC).
METHODS: Nine hundred and fifty-two NSCLC patients with lung cancer surgery
performed were enrolled into this study. The cutoffs of inflammatory response
biomarkers were determined by Receiver operating curve (ROC). Univariate and
multivariate analysis were conducted to select independent prognostic factors to
develop the nomogram. RESULTS: The median follow-up time was 40.0 months (range,
1 to 92 months). The neutrophil to lymphocyte ratio (cut-off: 3.10, HR:1.648, P =
0.045) was selected to establish the nomogram which could predict the 5-year OS
probability. The C-index of nomogram was 0.72 and the 5-year OS calibration curve
displayed an optimal agreement between the actual observed outcomes and the
predictive results. CONCLUSIONS: Neutrophil to lymphocyte ratio was shown to be a
valuable biomarker for predicting survival of patients with NSCLC. The addition
of neutrophil to lymphocyte ratio could improve the accuracy and predictability
of the nomogram in order to provide reference for clinicians to assess patient
outcomes.
PMID- 29940885
TI - The feasibility, acceptability and preliminary testing of a novel, low-tech
intervention to improve pre-hospital data recording for pre-alert and handover to
the Emergency Department.
AB - BACKGROUND: Poor communication during patient handover is recognised
internationally as a root cause of a significant proportion of preventable
deaths. Data used in handover is not always easily recorded using ambulance based
tablets, particularly in time-critical cases. Paramedics have therefore developed
pragmatic workarounds (writing on gloves or scrap paper) to record these data.
However, such practices can conflict with policy, data recorded can be variable,
easily lost and negatively impact on handover quality. METHODS: This study aimed
to measure the feasibility and acceptability of a novel, low tech intervention,
designed to support clinical information recording and delivery during pre-alert
and handover within the pre-hospital and ED setting. A simple pre and post-test
design was used with a historical control. Eligible participants included all
ambulance clinicians based at one large city Ambulance Station (n = 69) and all
nursing and physician staff (n = 99) based in a city Emergency Department.
RESULTS: Twenty five (36%) ambulance clinicians responded to the follow-up
survey. Most felt both the pre-alert and handover components of the card were
either 'useful-very useful' (n = 23 (92%); and n = 18 (72%) respectively.
Nineteen (76%) used the card to record clinical information and almost all (n =
23 (92%) felt it 'useful' to 'very useful' in supporting pre-alert. Similarly,
65% (n = 16) stated they 'often' or 'always' used the card to support handover.
For pre-alert information there were improvements in the provision of 8/11
(72.7%) clinical variables. Results from the post-test survey measuring ED staff
(n = 37) perceptions of handover demonstrated small (p < 0.05) improvements in
handover in 3/5 domains measured. CONCLUSION: This novel low-tech intervention
was highly acceptable to ambulance clinician participants, improving their data
recording and information exchange processes. However, further well conducted
studies are required to test the impact of this intervention on information
exchange during pre-alert and handover.
PMID- 29940886
TI - Titration of oxygen therapy in critically ill emergency department patients: a
feasibility study.
AB - BACKGROUND: Liberal use of oxygen in an emergency situation is common. Today,
most health care professionals do not adjust the amount of oxygen given when a
saturation of 100% or a PaO2 which exceeds the normal range is reached- which may
result in hyperoxia. There is increasing evidence for the toxic effects of
hyperoxia. Therefore, it seems justified to aim for normoxia when giving oxygen.
This study evaluates whether it is feasible to aim for normoxia when giving
oxygen therapy to patients at the emergency department (ED). METHODS: A
prospective cohort study was performed at the ED of the University Medical Center
Groningen (UMCG). A protocol was developed, aiming for normoxia. During a 14 week
period all patients > 18 years arriving at the ED between 8 a.m. and 23 p.m.
requiring oxygen therapy registered for cardiology, internal medicine, emergency
medicine and pulmonology were included. Statistical analysis was performed using
student independent t-test, Mann-Whitney U-test, Fisher's exact test or a
Pearson's chi-squared test. RESULTS: During the study period the study protocol
was followed and normoxia was obtained after 1 h at the ED in 86,4% of the
patients. Patients with COPD were more at risk for not being titrated to normal
oxygen levels. CONCLUSIONS: We showed that it is feasible to titrate oxygen
therapy to normoxia at the ED. The study results will be used for further
research assessing the potential beneficial effects of normoxia compared to hyper
or hypoxia in ED patients and for the development of guidelines.
PMID- 29940887
TI - Gene expression profile and cancer-associated pathways linked to progesterone
receptor isoform a (PRA) predominance in transgenic mouse mammary glands.
AB - BACKGROUND: Progesterone receptor (PR) is expressed from a single gene as two
isoforms, PRA and PRB. In normal breast human tissue, PRA and PRB are expressed
in equimolar ratios, but isoform ratio is altered during malignant progression,
usually leading to high PRA:PRB ratios. We took advantage of a transgenic mouse
model where PRA isoform is predominant (PRA transgenics) and identified the key
transcriptional events and associated pathways underlying the preneoplastic
phenotype in mammary glands of PRA transgenics as compared with normal wild-type
littermates. METHODS: The transcriptomic profiles of PRA transgenics and wild
type mammary glands were generated using microarray technology. We identified
differentially expressed genes and analyzed clustering, gene ontology (GO), gene
set enrichment analysis (GSEA), and pathway profiles. We also performed
comparisons with publicly available gene expression data sets of human breast
cancer. RESULTS: We identified a large number of differentially expressed genes
which were mainly associated with metabolic pathways for the PRA transgenics
phenotype while inflammation- related pathways were negatively correlated.
Further, we determined a significant overlap of the pathways characterizing PRA
transgenics and those in breast cancer subtypes Luminal A and Luminal B and
identified novel putative biomarkers, such as PDHB and LAMB3. CONCLUSION: The
transcriptional targets identified in this study should facilitate the
formulation or refinement of useful molecular descriptors for diagnosis,
prognosis, and therapy of breast cancer.
PMID- 29940888
TI - Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines.
AB - BACKGROUND: Investigators have hypothesized that omega-3 fatty acid
supplementation may modulate the immune response. However, available evidence is
conflicting. We performed this study to investigate the effect of prenatal
eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil
supplementation on maternal and fetal cytokine production. METHODS: This study is
a secondary analysis of a randomized controlled trial designed to assess whether
prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal
depressive symptoms among women at risk. Enrolled participants received EPA-rich
fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg
EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12-20
weeks gestation) and after supplementation (34-36 weeks gestation). Umbilical
cord blood was collected at delivery. We analyzed stored plasma specimens for 16
human cytokines using multiplex immunoassays. Maternal and cord blood cytokine
levels were compared among the treatment groups. Associations of serum DHA and
EPA with maternal and cord blood cytokines were explored via regression analysis.
RESULTS: We enrolled 126 women, of whom 118 completed the trial. Prenatal
supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15,
and TNFalpha concentrations. However, supplementation with DHA-rich fish oil had
no significant effect on maternal cytokine profiles. Maternal serum DHA fraction
was significantly associated with IL1alpha, and maternal serum DHA and EPA
fractions were significantly associated with IL 10 concentrations after
supplementation. Compared with placebo, supplementation with EPA- or DHA-rich
fish oils had no significant effect on cord blood cytokine concentrations.
CONCLUSIONS: Prenatal supplementation with EPA-rich fish oil significantly
reduced levels of several inflammatory cytokines in maternal plasma, while
prenatal DHA-rich fish oil had no significant effect on cytokine concentrations.
Supplementation with EPA- and DHA- rich fish oil had no significant effect on
umbilical cord blood cytokine concentrations. TRIAL REGISTRATION: Clinical Trial
Registration: registration number NCT00711971 7/7/2008.
PMID- 29940889
TI - Predictors of maternal near miss among women admitted in Gurage zone hospitals,
South Ethiopia, 2017: a case control study.
AB - BACKGROUND: Maternal mortality and morbidity remain unacceptably high in
developing countries. Behind every maternal death, many other women suffered from
acute and chronic obstetric complications. Women who survive severe acute
maternal morbidities/near miss have many characteristics in common with maternal
death events particularly on risk factors. Ethiopia is among countries with high
maternal mortality and morbidities in sub-Saharan Africa. However there is scarce
evidence on risk factors of severe acute maternal morbidities in Ethiopia.
Therefore this study aimed to identify predictors of maternal near miss among
women admitted in Gurage zone hospitals, south Ethiopia, 2017. METHODS: Hospital
based case control study was conducted to assess predictors of maternal near miss
among women admitted in five hospitals of Gurage zone, South Ethiopia. Data of
229 (77 cases and 152 controls) women were included in the analysis. Cases were
women admitted due to severe acute maternal morbidity while controls were women
admitted for normal labor or women admitted due to mild to moderate obstetric
complications. Cases were identified by validated-disease specific criteria.
Then, two controls were selected for each verified case using lottery method
among eligible women. Data were collected using interviewer administered
questionnaire and reviewing patients' records. Data were entered using Epi Info 7
and analyzed by SPSS 21. Multivariable logistic regression analysis was done to
identify independent predictors of maternal near miss. RESULT: Majority of cases
were admitted due to dystocia (57.1%) and obstetric hemorrhage (26%). The median
first delay (delay to seek health care) among cases and controls was six and 4 h
respectively. Prior history of cesarean section {AOR 7.68, 95%CI, 3.11-18.96},
first delay {AOR 2.79, 95%CI, 1.42-5.50}, and being referred from other health
facilities {AOR 7.47, 95% CI, 2.27-24.51} were independent predictors of maternal
near miss. CONCLUSIONS: Prior history of cesarean section, being referred from
other health facilities and first delay were factors associated with maternal
near miss. Timely health care seeking behavior of women is uncommon in the study
area. Therefore primary health care programs need to enhance the existing efforts
to improve timely health care seeking behavior of women.
PMID- 29940890
TI - Ending preventable maternal mortality: phase II of a multi-step process to
develop a monitoring framework, 2016-2030.
AB - BACKGROUND: In February 2015, the World Health Organization (WHO) released
"Strategies toward ending preventable maternal mortality (EPMM)" (EPMM
Strategies), a direction-setting report outlining global targets and strategies
for reducing maternal mortality in the Sustainable Development Goal (SDG) period.
In May 2015, the EPMM Working Group outlined a plan to develop a comprehensive
monitoring framework to track progress toward the achievement of these targets
and priorities. This monitoring framework was developed in two phases. Phase I,
which focused on identifying indicators related to the proximal causes of
maternal mortality, was completed in October 2015. This paper describes the
process and results of Phase II, which was completed in November 2016 and aimed
to build consensus on a set of indicators that capture information on the social,
political, and economic determinants of maternal health and mortality. FINDINGS:
A total of 150 experts from more than 78 organizations worldwide participated in
this second phase of the process to develop a comprehensive monitoring framework
for EPMM. The experts considered a total of 118 indicators grouped into the 11
key themes outlined in the EPMM report, ultimately reaching consensus on a set of
25 indicators, five equity stratifiers, and one transparency stratifier.
CONCLUSION: The indicators identified in Phase II will be used along with the
Phase I indicators to monitor progress towards ending preventable maternal
deaths. Together, they provide a means for monitoring not only the essential
clinical interventions needed to save lives but also the equally important
political, social, economic and health system determinants of maternal health and
survival. These distal factors are essential to creating the enabling environment
and high-performing health systems needed to ensure high-quality clinical care at
the point of service for every woman, her fetus and newborn. They complement and
support other monitoring efforts, in particular the "Survive, Thrive, and
Transform" agenda laid out by the Global Strategy for Women's, Children's and
Adolescents' Health (2016-2030) and the SDG3 global target on maternal mortality.
PMID- 29940891
TI - C3 glomerulonephritis and thrombotic microangiopathy of renal allograft after
pulmonary infection in a male with concomitant two complement factor I gene
variations: a case report.
AB - BACKGROUND: It has been suggested that C3 glomerulonephritis (C3GN) and atypical
hemolytic-uremic syndrome (a stereotypical phenotype of thrombotic
microangiopathy), two rare entities caused by complement alternative pathway
dysregulation share overlapping genetic origin and can be triggered by
infections. CASE PRESENTATION: We report a case of concomitant C3GN and
thrombotic microangiopathy (TMA) after pulmonary infection in a young male
receiving kidney transplantation. Genetic assessment revealed two missense
variations in compound heterozygous form in CFI gene (complement factor I). These
two variations are segregated with disease in the core family member of this
patient. Plasma CFI levels of the patient and family members were all in normal
range. We considered that these two variations only impair CFI function rather
than its quantity in the serum. CONCLUSION: Our case supports that C3GN and TMA
shared overlapping genetic variations and might be triggered by infection in
genetically susceptible patients after kidney transplantation.
PMID- 29940892
TI - Loss of expression and prognosis value of alpha-internexin in
gastroenteropancreatic neuroendocrine neoplasm.
AB - BACKGROUND: The neuronal intermediate filament alpha-internexin (alpha
internexin) is a cytoskeleton protein which is involved in the tumor initiation
and progression. In this study, we examined the expression and prognosis value of
alpha-internexin in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).
METHODS: alpha-internexin was detected with immunohistochemical staining in 286
tumor specimens from patients with GEP-NENs. Methylation status of alpha
internexin was evaluated by bisulfite genomic sequencing. We assessed the
prognostic value of alpha-internexin and its correlation with relevant
clinicalpathological characteristics. RESULTS: The reduced/loss of expression
rate of alpha-internexin in GEP-NEN was 73.4% (210/286), while the positive
expression rate was 26.6% (76/286). The difference of alpha-internexin deficiency
was not statistically significant between gastrointestinal NENs (GI-NENs) and
pancreatic NENs (pNENs). However, we found significant difference of reduced/loss
of alpha-internexin expression among different sites of GI-NENs (chi2 = 43.470, P
< 0.001). The reduced/loss of expression of alpha-internexin was significantly
associated with poorly differentiation (P < 0.001) and advanced tumor stage (P <
0.001). Univariate analyses showed that reduced/loss of expression of alpha
internexin predicted worse overall survival (OS) in GEP-NEN patients (P < 0.001),
especially in subtype of GI-NENs (P < 0.001). However, in multivariable
regression analysis, alpha-internexin expression was not an independent
prognostic factor. The hypermethylation of alpha-internexin gene was
significantly correlated with protein deficiency in GI-NENs, but not in pNENs.
Hypermethylation of several CpG sites was significantly associated with poorly
differentiated and advanced stage (P values range from 0.018 to 0.044). However,
the methylation status of alpha-internexin was not associated with patient OS.
CONCLUSIONS: The expression of alpha-internexin was highly heterougeneous in
different sites of GEP-NENs. The reduced/loss of expression of alpha-internexin
was closely related to tumors with aggressiveness and patient's adverse
prognosis. The hypermethylation of the regulatory region examined may be an
important epigenetic regulation mechanism of alpha-internexin deficiency in
subtype of GI-NENs.
PMID- 29940893
TI - The effect of low insurance reimbursement on quality of care for non-small cell
lung cancer in China: a comprehensive study covering diagnosis, treatment, and
outcomes.
AB - BACKGROUND: The insurance reimbursement rate of medical cost affects the quality
and quantity of health services provided in China. The nature of this
relationship, however, has not been reliably described in the field of non-small
cell lung cancer (NSCLC). The objective of the current study was to examine the
impact of low reimbursement rates of medical costs on diagnosis, treatment and
outcomes among patients with NSCLC. METHODS: We examined care of 2643 NSCLC
patients and we divided the study cohort into a high reimbursement rate group and
a low reimbursement rate group. The impact of reimbursement rates of medical
costs on quality of care of NSCLC patients were examined using logistic
regression and generalized linear models. RESULTS: Compared with patients insured
with high reimbursement rate, patients insured through lower reimbursement rate
programs were less likely to benefit from early detection and treatment services.
Delayed detection was more common in low reimbursement group and they were less
likely to be recommended for adjuvant chemotherapy, or to receive adjuvant
chemotherapy and postoperative radiation therapy and they had lower odds to
receipt chemotherapy response assessment. However, low reimbursement rate group
had lower rate of in-hospital mortality and metastases. CONCLUSIONS: Low
reimbursement rate mainly negatively influenced the diagnosis and treatment of
NSCLC. Reducing the gap in reimbursement rate between the three health insurance
schemes should be a focus of equalizing access to care and improving the level of
medical compliance and finally improving quality of care of NSCLC.
PMID- 29940894
TI - Replacing sedentary time with physical activity or sleep: effects on cancer
related cognitive impairment in breast cancer survivors.
AB - BACKGROUND: Evidence suggests reallocating daily sedentary time to physical
activity or sleep confers important health benefits in cancer survivors. Despite
emerging research suggesting physical activity as a treatment for cancer-related
cognitive impairment (CRCI), little is known about the interactive effects of
behaviors across the 24-h period. The present purpose was to examine the
cognitive effects of reallocating sedentary time to light-intensity physical
activity, moderate-to-vigorous physical activity (MVPA), or sleep in breast
cancer survivors. METHODS: Breast cancer survivors (N = 271, Mage = 57.81 +/-
9.50 years) completed iPad-based questionnaires and cognitive tasks assessing
demographics, health history, executive function, and processing speed (Task
Switch, Trail Making). Participants wore an accelerometer for seven consecutive
days to measure their sedentary, physical activity, and sleep behaviors. Single
effects (each behavior individually) and partition (controlling for other
behaviors) models were used to examine associations among behaviors and cognitive
performance. Isotemporal substitution models were used to test the cognitive
effects of substituting 30 min of sedentary time with 30 min of light-intensity
activity, MVPA, and sleep. RESULTS: MVPA was associated with faster Task-switch
reaction time in the partition models (stay: B = - 35.31, p = 0.02; switch: B = -
48.24, p = 0.004). Replacing 30 min of sedentary time with 30 min of MVPA yielded
faster reaction times on Task-Switch stay (B = - 29.37, p = 0.04) and switch (B =
- 39.49, p = 0.02) trials. In Trails A single effects models, sedentary behavior
was associated with faster completion (B = - 0.97, p = 0.03) and light-intensity
activity with slower completion (B = 1.25, p = 0.006). No single effects were
observed relative to Trails B completion (all p > 0.05). Only the effect of MVPA
was significant in the partition models (Trails A: B = - 3.55, p = 0.03; Trails
B: B = - 4.46, p = 0.049). Replacing sedentary time with light-intensity activity
was associated with slower Trails A (B = 1.55 p = 0.002) and Trails B (B = 1.69,
p = 0.02) completion. Replacing light activity with MVPA yielded faster Trails A
(B = - 4.35, p = 0.02) and Trails B (B = - 5.23, p = 0.03) completion.
CONCLUSIONS: Findings support previous research suggesting MVPA may be needed to
improve cognitive function in breast cancer survivors. Trails findings underscore
the need to dissect sedentary contexts to better understand the impact of daily
behavioral patterns on CRCI. Additional research investigating the cognitive
impacts of behaviors across the 24-h period is warranted. TRIAL REGISTRATION:
This study is registered with United States ClinicalTrials.gov ( NCT02523677 ;
8/14/2015).
PMID- 29940895
TI - MicroRNA-29b-2-5p inhibits cell proliferation by directly targeting Cbl-b in
pancreatic ductal adenocarcinoma.
AB - BACKGROUND: MicroRNAs can be used in the prognosis of malignancies; however,
their regulatory mechanisms are unknown, especially in pancreatic ductal
adenocarcinoma (PDAC). METHODS: In 120 PDAC specimens, miRNA levels were assessed
by quantitative real time polymerase chain reaction (qRT-PCR). Then, the role of
miR-29b-2-5p in cell proliferation was evaluated both in vitro (Trypan blue
staining and cell cycle analysis in the two PDAC cell lines SW1990 and Capan-2)
and in vivo using a xenograft mouse model. Next, bioinformatics methods, a
luciferase reporter assay, Western blot, and immunohistochemistry (IHC) were
applied to assess the biological effects of Cbl-b inhibition by miR-29b-2-5p.
Moreover, the relationship between Cbl-b and p53 was evaluated by
immunoprecipitation (IP), Western blot, and immunofluorescence. RESULTS: From the
120 PDAC patients who underwent surgical resection, ten patients with longest
survival and ten with shortest survival were selected. We found that high miR-29b
2-5p expression was associated with good prognosis (p = 0.02). The validation
cohort confirmed miR-29b-2-5p as an independent prognostic factor in PDAC (n =
100, 95% CI = 0.305-0.756, p = 0.002). Furthermore, miR-29b-2-5p inhibited cell
proliferation, induced cell cycle arrest, and promoted apoptosis both in vivo and
in vitro. Interestingly, miR-29b-2-5p directly bound the Cbl-b gene, down
regulating its expression and reducing Cbl-b-mediated degradation of p53.
Meanwhile, miR-29b-2-5p expression was negatively correlated with Cbl-b in PDAC
tissues (r = - 0.33, p = 0.001). CONCLUSIONS: Taken together, these findings
indicated that miR-29b-2-5p improves prognosis in PDAC by targeting Cbl-b to
promote p53 expression, and would constitute an important prognostic factor in
PDAC.
PMID- 29940896
TI - Oral cancer incidence in Shanghai ---- a temporal trend analysis from 2003 to
2012.
AB - BACKGROUND: Oral cancer is a serious problem owing to its poor prognosis and
destruction of patients' eating ability as well as facial appearance.
Epidemiological studies can provide aetiological clues for prevention. The
prevalence of oral cancer in densely populated cities in eastern China is
unclear. The aim of the study is to analyse the incidence rates of oral cancer in
Shanghai over the period 2003-2012 and estimate the temporal trends. METHODS:
Cases of oral cancer were retrieved from the Shanghai Cancer Registry system in
the Shanghai Municipal Center for Disease Control & Prevention for the years 2003
to 2012. Information on the corresponding population was obtained from the
Shanghai Municipal Bureau of Public Security. Age-standardised incidence rates
were directly calculated according to the world standard population. An annual
percent change model was employed to analyse the temporal trends of cancer
incidence. RESULTS: A total of 3860 oral cancer cases were reported, representing
0.69% of all malignancies in Shanghai during the 10-year study period. The mean
age at diagnosis was 64 years. The age-standardised incidence rate was 1.34 per
100,000 person-years, with a male-to-female ratio of 1.41. Annually, the
incidence rates increased by 3.83 and 2.54% for men and women, respectively. The
increase was most noticeable in males aged 45-64 years. CONCLUSION: In Shanghai,
the oral cancer incidence is relatively low. However, it is continuously
increasing, especially among middle-aged males. This finding urges further
investigations on the risk factors of oral cancer in this population, especially
on changes in living patterns, such as the smoking, drinking, and dietary habits.
PMID- 29940897
TI - The economic consequences of attention-deficit hyperactivity disorder in the
Scottish prison system.
AB - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is highly prevalent
amongst prison inmates and the criminal justice system (CJS) likely bears
considerable costs for offenders with ADHD. We aimed to examine the relationship
between ADHD and health-related quality of life (HRQoL) and quality-adjusted life
years (QALY) amongst imprisoned adults; and to estimate the annual expenditure
associated with ADHD status in prison. METHODS: An observational study was
performed in 2011-2013, at Porterfield Prison, Inverness, United Kingdom (UK).
The all male sample included 390 adult prison inmates with capacity to consent
and no history of moderate or severe intellectual disability. Participants were
interviewed using the Diagnostic Interview for ADHD in Adults 2.0. The Health
Utilities Index Mark 3 (HUI3) was used to measure health status, and to calculate
attribute specific HRQoL scores and QALY. Health service utilisation was obtained
through inspection of medical prison records. Inmates with ADHD were compared
with inmates without ADHD. RESULTS: Inmates with ADHD had significantly lower
QALYs, with a clinically significant adjusted difference of 0.13. Psychiatric co
morbidity accounted for the variation of ADHD on the HUI3 emotion domain only.
Medical costs for inmates with ADHD were significantly higher; and behaviour
related prison costs were similar to prisoners without ADHD, reflecting a low
frequency of recorded critical incidents. CONCLUSIONS: ADHD may directly
contribute to adverse health and quality of life through cognitive and executive
function deficits, and co-morbid disorders. The extrapolation of conservative
cost estimates suggests that the financial burden of medical and behavior-related
prison care for inmates with ADHD in the UK is approximately L11.7 million
annually. The reported cost estimates are conservative as there is great
variability in recorded critical incidents in prisons. In turn, for some prison
establishments the prison care costs associated with prisoners with ADHD may be
considerably greater.
PMID- 29940898
TI - Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and
hepatic cancer cells.
AB - BACKGROUND: We previously showed that knockdown of nuclear factor E2-related
factor 2 (Nrf2) resulted in suppression of hepatitis C virus (HCV) infection. In
this study, whether brusatol, an Nrf2 inhibitor, has dual anti-HCV and anticancer
effects was explored. METHODS: The anti-HCV effect of brusatol was investigated
by analyzing HCV RNA and proteins in a hepatic cell line persistently-infected
with HCV, HPI cells, and by analyzing HCV replication in a replicon-replicating
hepatic cell line, OR6 cells. Then, dual anti-HCV and anticancer effects of
brusatol and enhancement of the effects by the combination of brusatol with
anticancer drugs including sorafenib, which has been reported to have the dual
effects, were then investigated. RESULTS: Brusatol suppressed the persistent HCV
infection at both the RNA and protein levels in association with a reduction in
Nrf2 protein in the HPI cells. Analysis of the OR6 cells treated with brusatol
indicated that brusatol inhibited HCV persistence by inhibiting HCV replication.
Combination of brusatol with an anticancer drug not only enhanced the anticancer
effect but also, in the case of the combination with sorafenib, strongly
suppressed HCV infection. CONCLUSIONS: Brusatol has dual anti-HCV and anticancer
effects and can enhance the comparable effects of sorafenib. There is therefore
the potential for combination therapy of brusatol and sorafenib for HCV-related
hepatocellular carcinoma.
PMID- 29940899
TI - Comparison of 5-year progression of retinitis pigmentosa involving the posterior
pole among siblings by means of SD-OCT: a retrospective study.
AB - BACKGROUND: The aim of this study is to analyze and compare the progression of
photoreceptor atrophy among siblings affected by retinitis pigmentosa by means of
spectral SD-OCT. METHODS: Fifty three eyes of 27 patients belonging to 12 family
clusters were analyzed. To assess the annual progression rate of photoreceptor
atrophy, the ellipsoid zone (EZ) line was measured in OCT sections through the
fovea. We used multivariate generalized mixed effects to model the rate of
progression and its relation to the initial ellipsoid zone line width. RESULTS:
During our 4.84 years (+/- 1.44) mean follow up time (range 3-7) 53 eyes were
examined. The ellipsoid zone line width declined with a yearly average rate of
76.4 MUm (4.16% / year) (p-value < 0.0001). Progression rates were poorly
correlated within family clusters (p-value = 0.23) and showed statistical
difference between affected siblings (p-value = 0.007). There was no correlation
between inter-familiar progression rate and mode of inheritance (p-value = 0.98)
as well as between age and ellipsoid zone line width among siblings (p-value =
0.91). CONCLUSION: RP could be extremely heterogeneous even among siblings: an
accurate and sensitive method to follow the progression of the disease is
fundamental for future development of clinical trials and therapy strategies.
PMID- 29940900
TI - Outcomes and prognostic factors for aggressive posterior retinopathy of
prematurity following initial treatment with intravitreal ranibizumab.
AB - BACKGROUND: This study sought to identify factors associated with retinal
detachment and retreatment of aggressive posterior retinopathy of prematurity
(APROP) initially treated with intravitreal ranibizumab (IVR) injection as well
as the efficacy of IVR treatment. METHODS: This was a retrospective study. A
total of 83 preterm infants (160 eyes) diagnosed with APROP who were primarily
treated with IVR were included. The 160 eyes were divided into two groups based
on the anatomic outcomes. Group A included 35 eyes that developed retinal
detachment, and Group B included 125 eyes without retinal detachment. The
following patient factors were retrospectively reviewed: gender, gestational age
(GA), birth weight (BW), postmenstrual age (PMA) at first treatment, iris
neovascularizations, retinal hemorrhage, neutrophil and lymphocyte counts before
the first intravitreal injection, neutrophil-to-lymphocyte ratio (NLR),
anatomical outcomes, additional treatment and follow-up time. Three dummy
variables were created as dependent variables based on the methods of
retreatment. The possible risk factors for APROP were evaluated, and statistical
analyses included univariate and multivariate logistic regression. RESULTS: A
total of 160 eyes from 83 preterm infants (56 males and 27 females) underwent
initial IVR treatment with a follow-up time of 17.17 +/- 10.54 months. Thirty
five of the 160 (21.9%) eyes progressed to retinal detachment, and 82 of the 125
(65.6%) non-retinal detachment eyes needed retreatment, with favorable anatomical
outcomes. The disease improved approximately 1.5 +/- 1.2 weeks after the first
IVR treatment. The mean recurrence period of APROP was approximately 7.5 +/- 6.9
weeks after the first IVR treatment. Multiple logistic regression analysis
revealed postmenstrual age (P < 0.001) and neutrophil count (P = 0.009) as the
most significant factors for retinal detachment in APROP. Retinal hemorrhage (P =
0.007) and BW (P = 0.04) were most significantly associated with APROP recurrence
and retreatment. CONCLUSIONS: IVR injection is an effective treatment for APROP.
In this study, older postmenstrual age and low neutrophil count were identified
as risk factors for retinal detachment in APROP. In addition, retinal hemorrhage
and low BW were significantly associated with recurrence and retreatment in non
retinal detachment APROP. Thus, patients with a lower BW, older postmenstrual
age, low neutrophil count and retinal hemorrhage should be reexamined in a timely
and more frequent manner.
PMID- 29940901
TI - Antarctica eye study: a prospective study of the effects of overwintering on
ocular parameters and visual function.
AB - BACKGROUND: In 2013 five polar explorers attempted to complete the first Trans
Antarctic Winter Traverse (TAWT). This study presents the ophthalmological
findings for this group, who overwintered in Antarctica as part of the White Mars
Human Science Protocol. Antarctic crews are exposed to extreme cold, chronic
hypoxia and altered day-night cycles. Previous studies of Antarctic explorers
have focused on the prolonged effect of ultraviolet radiation including the
development of ultraviolet keratitis and accelerated cataract formation. This is
the first study of its kind to investigate the effect of overwintering in
Antarctica on the human eye. METHODS: Pre and post-expedition clinical
observations were made including visual acuity, contrast sensitivity, colour
vision, auto-refraction, subjective refraction, retinal examination, retinal
autofluoresence and retinal thickness, which were graded for comparison. During
the expedition additional observations were made on a monthly basis including
LogMAR visual acuity, autorefraction and intraocular pressure. RESULTS: No
significant differences between pre and post-expedition observations were found,
including visual acuity, contrast sensitivity, colour vision, refraction, visual
fields, intraocular pressure and retinal examination. There was a small but
statistically significant decrease in retinal thickness across all regions of the
retina, except for the macular and fovea, in all explorers. Intra-expedition
observations remained within normal limits. CONCLUSION: Reassuringly, the human
eye remains largely unchanged by exposure to the extreme conditions encountered
during the Antarctic winter, however, further research is needed to investigate
changes in retinal thickness. This may have implications for scientists who spend
prolonged periods of time in the polar regions, as well as those who have
prolonged exposure to the extreme cold or chronic hypoxia in other settings.
PMID- 29940902
TI - Thirsty? Choose Water! Behavioural interventions and water stations in secondary
schools a two-by-two factorial randomised controlled trial.
AB - BACKGROUND: Childhood overweight and obesity is a significant public health
issue. A key contributing factor is sugar sweetened beverages (SSBs) consumption.
Evidence suggests that secondary school students are frequent consumers of SSBs,
with high daily consumption. The promotion of water consumption and provision of
chilled water stations can reduce SSBs consumption. The Thirsty Choose Water!
study will evaluate the effectiveness of two interventions, a behavioural
intervention, Thirsty? Choose Water! behavioural intervention (TCW-BI), that
target students through the domains of the health promoting high schools
framework, and the second intervention is the installation and promotion of
chilled water stations. METHODS/DESIGN: This community trial will recruit 60
secondary schools from across three Local Health Districts (LHDs) within New
South Wales (NSW). A two-by-two factorial study design will be used to determine
the effect of the Thirsty? Choose Water! behavioural intervention (TCW-BI), and
the installation of chilled water stations. The recruited secondary schools will
be randomised and non-blinded to one of four study arms receiving either the TCW
BI or chilled water stations, both interventions, or neither (control group).
Baseline measures will be collected including student self-report surveys which
will gather data regarding knowledge, attitudes and consumption of water and
SSBs, a school profile and an environmental scan. Student surveys will be
repeated post the intervention and at follow-up. Regular water meter readings
will determine the water flow from the chilled water stations across the study
period. DISCUSSION: There is an increasing body of evidence which suggests that
decreasing consumption of SSBs can impact positively on childhood overweight and
obesity. However, in the Australian context there are limited studies on how this
may occur in the secondary school setting. This study will add to this evidence
base and establish the effectiveness of TCW-BI and chilled water stations, either
alone or combination on increasing water consumption in adolescents. Information
about barriers and facilitators to implementation will be documented. Packages to
support the implementation of the TCW-BI as a state-wide initiative will be
developed. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials
Register ACTRN12618000526279 April 2018.
PMID- 29940903
TI - Evaluation of the impact of immunization policies, including the addition of
pharmacists as immunizers, on influenza vaccination coverage in Nova Scotia,
Canada: 2006 to 2016.
AB - BACKGROUND: Influenza is a serious public health concern, resulting in morbidity,
mortality and significant expense to healthcare systems worldwide. Annual
vaccination is the most effective way to prevent influenza. The National Advisory
Committee on Immunization in Canada recommends that everyone six months of age
and older without contraindications should be vaccinated. The Canadian province
of Nova Scotia implemented a publicly-funded universal influenza vaccination
program in the 2010-2011 influenza season. In 2013, pharmacists in Nova Scotia
gained the authority to provide a variety of vaccinations, including the publicly
funded influenza vaccine. This study aimed to investigate any changes in
influenza vaccine coverage following the implementation of each policy change: 1)
universal publicly-funded program and 2) universal publicly-funded program with
the addition of pharmacists. METHODS: Influenza seasons evaluated were from 2006
2007 to 2015-2016. Coverage was estimated by examining Nova Scotia census data
with aggregate immunization administration data, including the total number of
vaccinations administered according to vaccine provider (physician, public health
or pharmacist), geographic region, vaccine recipient age and year. RESULTS: The
analysis showed an increase in influenza vaccine coverage immediately following
the implementation of the two studied policy changes. Vaccine coverage increased
from 36.4 to 38% following the implementation of the universally funded vaccine
policy. Following the implementation of pharmacists as immunizers, coverage
increased from 35.7 to 41.7%. Vaccine coverage was highest in those 65 years of
age and older during all years evaluated. Physicians provided the highest
proportion of vaccines during all study periods, however a decreasing trend
through all periods was observed. Physicians proportionately provided more
vaccines in urban areas; whereas pharmacist and public health immunization
providers in rural areas provided proportionately more vaccinations than their
urban counterparts. CONCLUSIONS: The addition of a universally funded vaccination
policy and the addition of pharmacists as providers of the influenza vaccine
resulted in increases in vaccine coverage initially. Additional research is
needed to determine the long-term impacts of the policy changes on vaccination
coverage and to identify other important factors affecting vaccine uptake.
PMID- 29940904
TI - A RCT to evaluate a totally automated, culturally-adapted telephone counselor for
increasing physical activity among physically inactive individuals in China.
AB - BACKGROUND: The prevalence of diabetes in China has rapidly increased in recent
years. Family history and physical inactivity are known risk factors for
developing diabetes. As automated telephone-based communication is recognized as
a cost-effective health promoting device, the present study aims at evaluating
the efficacy of an automated telephone counselor (TLC-PA-China) for promoting
physical activity to the WHO-recommended level among physically inactive family
members of diabetes patients. METHODS: This study employed a parallel, two-group,
non-blinded, randomized controlled trial design with equal allocation to the
intervention group (TLC-PA-China), and a control group. Voluntary participants
with at least one first-degree relative diagnosed with diabetes mellitus were
recruited through eight Community Health Centers in Shenzhen, China. The
intervention group was requested to use the system once per week during a six
month period. The control group received an information pamphlet about the
benefits of regular physical activity. RESULTS: Two hundred ten eligible
participants were randomized to TLC-PA-China (n = 109) or Control (n = 101)
groups. Using intention-to-treat analysis, the TLC-PA-China group was
significantly more likely to meet the WHO physical activity recommendation than
the control (GEE: OR = 6.37, p < 0.001). The number of physically inactive people
to intervene upon for one to become active was 2.84 at 3 months and 3.31 at 6
months. CONCLUSIONS: TLC-PA-China increased physical activity levels among
physically inactive adults in China who were at high risk of developing diabetes.
This study lays the groundwork for application of behavioral informatics
intervention in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR
PRC-13003361 . Registered 15 May 2013 (Retrospectively registered).
PMID- 29940905
TI - Shaping ability of protaper next compared with waveone in late-model three
dimensional printed teeth.
AB - BACKGROUND: Comparison of the shaping ability of advanced nickel-titanium (Ni-Ti)
instruments is of great interest to the field of endodontics. However, the models
used to study canal preparation still lack uniformity, relevance to reality and
complexity. The aim of this study was thus to compare the shaping abilities of
the ProTaper Next (PN) and WaveOne (WO) Ni-Ti instruments in three-dimensional
(3D)-printed teeth, which may overcome the present defects of most real teeth and
model teeth including 3D S-shaped canals. METHODS: Six teeth and their
corresponding 3D-printed replicas were prepared using the same kind of Ni-Ti
instrument. The pre- and post-preparation volumes, surface areas and
transportation of the canals were measured to compare the teeth with their
replicas. Twenty 3D-printed teeth with S-shaped canals were used to support the
preparation study. The S-shaped canals were then scanned to measure their volumes
and surface areas. Next, the two kinds of instruments were used to prepare the 3D
printed canals (n = 10 per group). The volume and surface area of the canals, the
transportation along the two curvatures and the percentage of unprepared surface
area were measured. Micro-CT and VGstudio2.2 (VG2.2) software were used to
perform scans and collect data throughout the research. The paired-samples T test
and Kruskal-Wallis H test were used for statistical analysis. RESULTS: There was
no significant difference between the real canals and the printed ones post
preparation (P > .05). The printed S-shaped root canals had a unified shape, with
a small standard deviation and range. The WO group had higher mean values for the
volume and superficial area measurements compared with the PN group (P < .05). No
differences in the untouched areas were found between the two systems (P > .05).
PN caused less transportation at the apical curve than WO did (P < .05).
CONCLUSIONS: In conclusion, 3D-printed teeth are suitable for the study of Ni-Ti
rotary instruments. Furthermore, the PN rotary system caused less transportation
at the apical curve than the WO system did in complicated root canal procedures.
PMID- 29940906
TI - Modelling the impact of social protection on tuberculosis: the S-PROTECT project.
AB - BACKGROUND: Tackling the social determinants of Tuberculosis (TB) through social
protection is a key element of the post-2015 End TB Strategy. However, evidence
informing policies are still scarce. Mathematical modelling has the potential to
contribute to fill this knowledge gap, but existing models are inadequate. The S
PROTECT consortium aimed to develop an innovative mathematical modelling approach
to better understand the role of social protection to improve TB care, prevention
and control. METHODS: S-PROTECT used a three-steps approach: 1) the development
of a conceptual framework; 2) the extraction from this framework of three high
priority mechanistic pathways amenable for modelling; 3) the development of a
revised version of a standard TB transmission model able to capture the structure
of these pathways. As a test case we used the Bolsa Familia Programme (BFP), the
Brazilian conditional cash transfer scheme. RESULTS: Assessing one of these
pathways, we estimated that BFP can reduce TB prevalence by 4% by improving
households income and thus their nutritional status. When looking at the direct
impact via malnutrition (not income mediated) the impact was 33%. This variation
was due to limited data availability, uncertainties on data transformation and
the pathway approach taken. These results are preliminary and only aim to serve
as illustrative example of the methodological challenges encountered in this
first modelling attempt, nonetheless they suggest the potential added value of
integrating TB standard of care with social protection strategies. CONCLUSIONS:
Results are to be confirmed with further analysis. However, by developing a
generalizable modelling framework, S-PROTECT proved that the modelling of social
protection is complex, but doable and allowed to draw the research road map for
the future in this field.
PMID- 29940907
TI - Exploiting routinely collected severe case data to monitor and predict influenza
outbreaks.
AB - BACKGROUND: Influenza remains a significant burden on health systems. Effective
responses rely on the timely understanding of the magnitude and the evolution of
an outbreak. For monitoring purposes, data on severe cases of influenza in
England are reported weekly to Public Health England. These data are both readily
available and have the potential to provide valuable information to estimate and
predict the key transmission features of seasonal and pandemic influenza.
METHODS: We propose an epidemic model that links the underlying unobserved
influenza transmission process to data on severe influenza cases. Within a
Bayesian framework, we infer retrospectively the parameters of the epidemic model
for each seasonal outbreak from 2012 to 2015, including: the effective
reproduction number; the initial susceptibility; the probability of admission to
intensive care given infection; and the effect of school closure on transmission.
The model is also implemented in real time to assess whether early forecasting of
the number of admissions to intensive care is possible. RESULTS: Our model of
admissions data allows reconstruction of the underlying transmission dynamics
revealing: increased transmission during the season 2013/14 and a noticeable
effect of the Christmas school holiday on disease spread during seasons 2012/13
and 2014/15. When information on the initial immunity of the population is
available, forecasts of the number of admissions to intensive care can be
substantially improved. CONCLUSION: Readily available severe case data can be
effectively used to estimate epidemiological characteristics and to predict the
evolution of an epidemic, crucially allowing real-time monitoring of the
transmission and severity of the outbreak.
PMID- 29940908
TI - How do social-economic differences in urban areas affect tuberculosis mortality
in a city in the tri-border region of Brazil, Paraguay and Argentina.
AB - BACKGROUND: The World Health Organization (WHO) launched the "End TB Strategy",
which aims to reduce tuberculosis (TB) mortality by 95% by 2035, Brazil has made
a commitment to this, however, one challenge is achieving the goal in the border
region, where the TB situation is more critical. The proposal was to analyse the
spatial mortality due to TB and its socio-economic determinants in the general
population, around the border areas of Brazil, Paraguay and Argentina, as well as
the temporal trend in this region. METHOD: This ecological study considered the
cases of TB deaths of residents of Foz do Iguacu (BR), with its units of analysis
being the census sectors. The standardized mortality rate was calculated for each
area. Socioeconomic variables data were obtained from the 2010 Demographic Census
of the Brazilian Institute of Geography and Statistics (IBGE). The scan statistic
was applied to calculate the spatial relative risk (RR), considering a 95%
confidence interval (CI). Spatial dependence was analysed using the Global
Bivariate Moran I and Local Bivariate Moran I (LISA) to test the relationship
between the socioeconomic conditions of the urban areas and mortality from TB.
Analysis of the temporal trend was also performed using the Prais-Winsten test.
RESULTS: A total of 74 cases of TB death were identified, of which 53 (71.6%)
were male and 51 (68.9%) people of white skin colour. The mortality rate ranged
from 0.28 to 22.75 cases per 100,000 inhabitants. A spatial relative risk area
was identified, RR = 5.07 (95% CI 1.79-14.30). Mortality was associated with:
proportion of people of brown skin colour (I: 0.0440, p = 0.033), income (low
income I: - 0.0611, p = 0.002; high income I: - 0.0449, p = 0.026) and density of
residents (3 and 4 residents, I: 0.0537, p = 0.007; 10 or more residents, I: -
0.0390, p = 0.035). There was an increase in the mortality rate in people of
brown skin colour (6.1%; 95% CI = 0.029, 0.093). CONCLUSION: Death due to TB was
associated with income, race resident density and social conditions. Although the
TB mortality rate is stationary in the general population, it is increasing among
people of brown skin colour.
PMID- 29940909
TI - High expression of the p53 isoform gamma is associated with reduced progression
free survival in uterine serous carcinoma.
AB - BACKGROUND: Uterine serous carcinoma (USC) is a rare but aggressive subtype of
endometrial carcinoma. Large-scale comprehensive efforts have resulted in an
improved molecular understanding of its pathogenesis, and the p53 pathway has
been proposed as a key player and is potentially targetable. Here we attempt to
further portray the p53 pathway in USC by assessing p53 isoform expression.
METHODS: We applied quantitative Real-Time PCRs (RT-qPCR) for expression analyses
of total p53 mRNA as well as quantitative distinction of p53beta, p53gamma, and
the total mRNA of amino-terminal truncated Delta40p53 and Delta133p53 in a
retrospective cohort of 37 patients with USC. TP53 mutation status was assessed
by targeted massive parallel sequencing. Findings were correlated with clinical
data. RESULTS: The p53 isoform expression landscape in USCs was heterogeneous and
dominated by total Delta133p53, while the distinct p53beta and p53gamma variants
were found at much lower levels. The isoform expression profiles varied between
samples, while their expression was independent of TP53 mutation status. We found
high relative p53gamma expression to be associated with reduced progression-free
survival (PFS). CONCLUSIONS: This is the first indication that elevated p53gamma
expression is associated with reduced PFS in USC. This single-center study may
offer some insight in the landscape of p53 isoform expression in USC, but further
validation studies are crucial to understand the context-dependent and tissue
specific role of the p53 isoform network in gynecological cancer.
PMID- 29940910
TI - Trends in pancreatic adenocarcinoma incidence and mortality in the United States
in the last four decades; a SEER-based study.
AB - BACKGROUND: Pancreatic cancer is the fourth-leading cause of cancer deaths in the
United States. The silent nature of the disease and its poor prognosis, the need
for further research, along with the need to assess the outcomes of current
approaches necessitate an ongoing evaluation of the epidemiology and mortality
trends of this malignancy. Continuous monitoring of disease-patterns, on
population-levels, may help scientists assess the quality of healthcare delivery,
boost their understanding of diseases' characteristics and risk factors, and
detect gaps whereby further research is needed. None of the previous reports shed
light on pancreatic adenocarcinomas (PAC), the most common type of Pancreatic
Cancer, as the primary outcome. In this study we aim to investigate PAC's
incidence and mortality trends over the last four decades in the United States.
METHODS: We used SEER 9 database to study PAC cases during 1974-2014. Incidence
and mortality rates were calculated by sex, age, race, state and stage of PAC.
Annual percent change (APC) was calculated using joinpoint regression software.
RESULTS: We reviewed 67,878 PAC cases; most of these cases were in the head of
pancreas. Overall PAC incidence rates increased 1.03% (95% CI, 0.86-1.21, p
<.001) per year over the study period. Rates of adenocarcinoma of the head of
pancreas increased 0.87% (95% CI, 0.68-1.07, p <.001), and rates of
adenocarcinoma of the body and tail of pancreas increased 3.42% (95% CI, 3.06
3.79, p <.001) per year during 1973-2014. PAC incidence-based mortality increased
2.22% (95% CI, 1.93-2.51, p <.001) per year. However, during 2012-2014 there was
a statistically significant decrease in PAC incidence-based mortality; APC,
24.70% (95% CI, -31.78 - -16.88, p <.001). CONCLUSION: PAC's incidence and
mortality rates have been increasing for decades. However, the last few years
have shown a promising decrease in mortality. We believe that further advances in
healthcare delivery and research can lead to a further mortality decrease. Future
studies can use this paper as a baseline to keep monitoring the outcomes of PAC's
therapy.
PMID- 29940911
TI - Benzylserine inhibits breast cancer cell growth by disrupting intracellular amino
acid homeostasis and triggering amino acid response pathways.
AB - BACKGROUND: Cancer cells require increased levels of nutrients such as amino
acids to sustain their rapid growth. In particular, leucine and glutamine have
been shown to be important for growth and proliferation of some breast cancers,
and therefore targeting the primary cell-surface transporters that mediate their
uptake, L-type amino acid transporter 1 (LAT1) and alanine, serine, cysteine
preferring transporter 2 (ASCT2), is a potential therapeutic strategy. METHODS:
The ASCT2 inhibitor, benzylserine (BenSer), is also able to block LAT1 activity,
thus inhibiting both leucine and glutamine uptake. We therefore aimed to
investigate the effects of BenSer in breast cancer cell lines to determine
whether combined LAT1 and ASCT2 inhibition could inhibit cell growth and
proliferation. RESULTS: BenSer treatment significantly inhibited both leucine and
glutamine uptake in MCF-7, HCC1806 and MDA-MB-231 breast cancer cells, causing
decreased cell viability and cell cycle progression. These effects were not
primarily leucine-mediated, as BenSer was more cytostatic than the LAT family
inhibitor, BCH. Oocyte uptake assays with ectopically expressed amino acid
transporters identified four additional targets of BenSer, and gas chromatography
mass spectrometry (GCMS) analysis of intracellular amino acid concentrations
revealed that this BenSer-mediated inhibition of amino acid uptake was sufficient
to disrupt multiple pathways of amino acid metabolism, causing reduced lactate
production and activation of an amino acid response (AAR) through activating
transcription factor 4 (ATF4). CONCLUSIONS: Together these data showed that
BenSer blockade inhibited breast cancer cell growth and viability through
disruption of intracellular amino acid homeostasis and inhibition of downstream
metabolic and growth pathways.
PMID- 29940912
TI - Heparan sulfate proteoglycans undergo differential expression alterations in left
sided colorectal cancer, depending on their metastatic character.
AB - BACKGROUND: Heparan sulfate proteoglycans (HSPGs) are complex molecules which
play a role in the invasion and growth and metastatic properties of cancerous
cells. In this work we analyze changes in the patterns of expression of HSPGs in
left sided colorectal cancer (LSCRC), both metastatic and non-metastatic, and the
results are also compared with those previously obtained for right sided tumors
(RSCRCs). METHODS: Eighteen LSCRCs were studied using qPCR to analyze the
expression of both the proteoglycan core proteins and the enzymes involved in
heparan sulfate chain biosynthesis. Certain HSPGs also carry chondroitin sulfate
chains and so we also studied the genes involved in its biosynthesis. The
expression of certain genes that showed significant expression differences were
also analysed using immunohistochemical techniques. RESULTS: Changes in
proteoglycan core proteins were dependent on their location, and the main
differences between metastatic and non-metastatic tumors affected cell-surface
glypicans, while other molecules were quite similar. Glypicans were also
responsible for the main differences between RS- and LS- malignances. Regarding
the biosynthesis of heparan sulfate chains, differential alterations in
transcription depending on the presence or not of metastasis affected genes
involved in the modification of uronic acid (epimerization and 2-O sulfation),
and some isoforms responsible for sulfation of glucosamine (NDST1, HS6ST1).
Moreover, in RSCRCs differences were preferentially found in the expression of
genes involved in C6 and C3 sulfation of glucosamine, but not in NDSTs or SULFs.
Finally, synthesis of chondroitin sulfate showed some alterations, which affected
various steps, including polimerization and the modification of chains, but the
main variations dependent on the presence of metastases were epimerization and 6C
sulfation; however, when compared with RSCRCs, the essential divergences affected
polymerization of the chains and the 6C sulfation of the galactosamine residue.
CONCLUSIONS: We evidenced alterations in the expression of HSPGs, including the
expression of cell surface core proteins, many glycosiltransferases and some
enzymes that modify the GAG chains in LSCRCs, but this was dependent on the
metastatic nature of the tumor. Some of these alterations are shared with RSCRCs,
while others, focused on specific gene groups, are dependent on tumor
localization.
PMID- 29940913
TI - Estimating the spatial risk of tuberculosis distribution in Gurage zone, southern
Ethiopia: a geostatistical kriging approach.
AB - BACKGROUND: In low-income countries it is difficult to obtain complete data that
show spatial heterogeneity in the risk of tuberculosis within-and-between smaller
administrative units. This may contribute to the partial effectiveness of
tuberculosis control programs. The aim of this study was to estimate the spatial
risk of tuberculosis distribution in Gurage Zone, Southern Ethiopia using limited
spatial datasets. METHODS: A total of 1601 patient data that were retrieved from
unit tuberculosis registers were included in the final analyses. The population
and geo-location data were obtained from the Central Statistical Agency of
Ethiopia. Altitude data were extracted from ASTER Global Digital Elevation Model
Version 2. Aggregated datasets from sample of 169(40%), 254(60%) and 338(80%)
kebeles were used to estimate the spatial risk of TB distribution in the Gurage
Zone by using a geostatistical kriging approach. The best set of input parameters
were decided based on the lowest prediction error criteria of the cross
validation technique. ArcGIS 10.2 was used for the spatial data analyses.
RESULTS: The best semivariogram models were the Pentaspherical, Rational
Quadratic, and K-Bessel for the 40, 60 and 80% spatial datasets, respectively.
The predictive accuracies of the models have improved with the true anisotropy,
altitude and latitude covariates, the change in detrending pattern from local to
global, and the increase in size of spatial dataset. The risk of tuberculosis was
estimated to be higher at western, northwest, southwest and southeast parts of
the study area, and crossed between high and low at west-central parts.
CONCLUSION: This study has underlined that the geostatistical kriging approach
can be applied to estimate the spatial risk of tuberculosis distribution in data
limited settings. The estimation results may help local public health authorities
measure burden of the disease at all locations, identify geographical areas that
require more attention, and evaluate the impacts of intervention programs.
PMID- 29940914
TI - A randomised controlled trial of the effect of providing online risk information
and lifestyle advice for the most common preventable cancers: study protocol.
AB - BACKGROUND: Cancer is a leading cause of mortality and morbidity worldwide.
Prevention is recognised by many, including the World Health Organization, to
offer the most cost-effective long-term strategy for the control of cancer. One
approach that focuses on individuals is the provision of personalised risk
information. However, whether such information motivates behaviour change and
whether the effect is different with varying formats of risk presentation is
unclear. We aim to assess the short-term effect of providing information about
personalised risk of cancer in three different formats alongside lifestyle advice
on health-related behaviours, risk perception and risk conviction. METHODS: In a
parallel group, randomised controlled trial 1000 participants will be recruited
through the online platform Prolific. Participants will be allocated to either a
control group receiving cancer-specific lifestyle advice alone or one of three
intervention groups receiving the same lifestyle advice alongside their estimated
10-year risk of developing one of the five most common preventable cancers,
calculated from self-reported modifiable behavioural risk factors, in one of
three different formats (bar chart, pictograph or qualitative scale). The primary
outcome is change from baseline in computed risk relative to an individual with a
recommended lifestyle at three months. Secondary outcomes include: perceived risk
of cancer; anxiety; cancer-related worry; intention to change behaviour; and
awareness of cancer risk factors. DISCUSSION: This study will provide evidence on
the short-term effect of providing online information about personalised risk of
cancer alongside lifestyle advice on risk perception and health-related
behaviours and inform the development of interventions. TRIAL REGISTRATION:
ISRCTN17450583. Registered 30 January 2018.
PMID- 29940915
TI - Communicating environmental exposure results and health information in a
community-based participatory research study.
AB - BACKGROUND: Communicating results to participants is a fundamental component of
community-based participatory research (CBPR). However, in environmental exposure
studies this is not always practiced, partly due to ethical concerns of
communicating results that have unknown clinical significance. METHODS: Growing
Up Healthy was a community-based participatory research study that sought to
understand the relationship between environmental exposures to phthalates and
early puberty in young girls. After in-depth consultation with a Community
Advisory Board, study investigators provided group summary results of phthalate
exposures and related health information to the parents of study participants.
Parents' comprehension and knowledge of the health information provided was then
assessed through questionnaires. RESULTS: After receiving the information from
the research team, responders were able to correctly answer comprehension
questions about phthalate exposures in their community, were able to identify
ways to reduce exposure to phthalates, and indicated plans to do so.
Questionnaires revealed that parents wanted more information on phthalates, and
that children's environmental health was an important concern. CONCLUSIONS: We
conclude that effective communication of exposure results of unknown clinical
significance to participants in environmental health studies can be achieved by
providing group summary results and actionable health information. Results
suggest that there was an improvement in knowledge of environmental health and in
risk reduction behaviors in our study population.
PMID- 29940916
TI - Estrogen-related receptors alpha, beta and gamma expression and function is
associated with transcriptional repressor EZH2 in breast carcinoma.
AB - BACKGROUND: Orphan nuclear receptors ERRalpha, ERRbeta and ERRgamma that belong
to NR3B or type IV nuclear receptor family are well studied for their role in
breast cancer pathophysiology. Their homology with the canonical estrogen
receptor dictates their possible contributing role in mammary gland development
and disease. Although function and regulation of ERRalpha, ERRgamma and less
about ERRbeta is reported, role of histone methylation in their altered
expression in cancer cells is not studied. Transcriptional activity of nuclear
receptors depends on co-regulatory proteins. The present study for the first time
gives an insight into regulation of estrogen-related receptors by histone
methylation specifically through methyltransferase EZH2 in breast cancer.
METHODS: Expression of ERRalpha, ERRbeta, ERRgamma and EZH2 was assessed by
immunohistochemistry in four identical tissue array slides that were prepared as
per the protocol. The array slides were stained with ERRalpha, ERRbeta, ERRgamma
and EZH2 simultaneously. Array data was correlated with expression in MERAV
expression dataset. Pearson correlation coeficient r was calculated from the
partial matrix expression values available at MERAV database to study the
strength of association between EZH2 and three orphan nuclear receptors under
study. By western blot and real time PCR, their correlated expression was studied
in breast cancer cell lines MCF-7, MDA-MB-231, T47D and MDA-MB-453 including
normal breast epithelial MCF-10A cells at both protein and RNA level. Regulation
of ERRalpha, ERRbeta, ERRgamma by EZH2 was further investigated upon
overexpression and silencing of EZH2. The interaction between ERRs and EZH2 was
validated in vivo by CHIP-qPCR. RESULTS: We found a negative correlation between
estrogen-related receptors and Enhancer of Zeste Homolog 2, a global repressor
gene. Immunohistochemistry in primary breast tumors of different grades showed a
correlated expression of estrogen-related receptors and EZH2. Their correlated
expression was further validated using online MERAV expression dataset where a
negative correlation of variable strengths was observed in breast cancer. Ectopic
expression of EZH2 in low EZH2-expressing normal breast epithelial cells
abrogated their expression and at the same time, its silencing enhanced the
expression of estrogen-related receptors in cancerous cells. Global occupancy of
EZH2 on ERRalpha and ERRbeta was observed in-vivo. CONCLUSION: Our findings
identify EZH2 as a relevant coregulator for estrogen-related receptors in breast
carcinoma.
PMID- 29940917
TI - Outcome of endoscopic trans-ethmosphenoid optic canal decompression for indirect
traumatic optic neuropathy in children.
AB - BACKGROUND: To evaluate the safety and outcomes of endoscopic trans-ethmosphenoid
optic canal decompression (ETOCD) for children with indirect traumatic optic
neuropathy (ITON). METHODS: From July 1st, 2008 to July 1st, 2015, 62 children
diagnosed with ITON who underwent ETOCD were reviewed. Main outcome measure was
improvement in visual acuity after treatment. RESULTS: Altogether 62 children (62
eyes) with a mean age of 11.26 +/- 4.14 years were included. Thirty-three (53.2%)
of them had residual vision before surgery while 29 (46.8%) had no light
perception (NLP). The overall visual acuity improvement rate after surgery was
54.84%. The improvement rate of patients with residual vision (69.70%) was
significant higher than that of patients with no light perception (NLP) (37.9%)
(P = 0.012). However, no significant difference was shown among patients with
different residual vision (P = 0.630). Presence of orbital and/ or optic canal
fracture and hemorrhage within the post-ethmoid and/or sphenoid sinus resulted in
poor postoperative visual acuity, duration of presenting complaints did not
affect final visual acuity or did not effect outcomes. Intervention performed in
children presenting even after 7 days from the injury did not influence the final
visual outcome. Three patients developed cerebrospinal fluid rhinorrhea and one
encountered cavernous sinus hemorrhage during surgery. No other severe
complications were observed. CONCLUSION: Children with residual vision had better
postoperative visual prognosis and benefited more from ETOCD than children with
NLP. Intervention performed in children presenting even after 7 days from the
injury did not influence the final visual outcome, however, this needs to be
reassessed in children presenting long after the injury.Treatment should still be
recommended even for cases of delayed presentation to hospital.
PMID- 29940918
TI - Impact of geographic distance on appraisal delay for active TB treatment seeking
in Uganda: a network analysis of the Kawempe Community Health Cohort Study.
AB - BACKGROUND: Appraisal delay is the time a patient takes to consider a symptom as
not only noticeable, but a sign of illness. The study's objective was to
determine the association between appraisal delay in seeking tuberculosis (TB)
treatment and geographic distance measured by network travel (driving and
pedestrian) time (in minutes) and distance (Euclidean and self-reported) (in
kilometers) and to identify other risk factors from selected covariates and how
they modify the core association between delay and distance. METHODS: This was
part of a longitudinal cohort study known as the Kawempe Community Health Study
based in Kampala, Uganda. The study enrolled households from April 2002 to July
2012. Multivariable interval regression with multiplicative heteroscedasticity
was used to assess the impact of time and distance on delay. The delay interval
outcome was defined using a comprehensive set of 28 possible self-reported
symptoms. The main independent variables were network travel time (in minutes)
and Euclidean distance (in kilometers). Other covariates were organized according
to the Andersen utilization conceptual framework. RESULTS: A total of 838
patients with both distance and delay data were included in the network analysis.
Bivariate analyses did not reveal a significant association of any distance
metric with the delay outcome. However, adjusting for patient characteristics and
cavitary disease status, the multivariable model indicated that each minute of
driving time to the clinic significantly (p = 0.02) and positively predicted 0.25
days' delay. At the median distance value of 47 min, this represented an
additional delay of about 12 (95% CI: [3, 21]) days to the mean of 40 days (95%
CI: [25, 56]). Increasing Euclidean distance significantly predicted (p = 0.02)
reduced variance in the delay outcome, thereby increasing precision of the mean
delay estimate. At the median Euclidean distance of 2.8 km, the variance in the
delay was reduced by more than 25%. CONCLUSION: Of the four geographic distance
measures, network travel driving time was a better and more robust predictor of
mean delay in this setting. Including network travel driving time with other risk
factors may be important in identifying populations especially vulnerable to
delay.
PMID- 29940919
TI - Workplace social capital and mental health: a cross-sectional study among Iranian
workers.
AB - BACKGROUND: The psychosocial environment of the workplace has received less
attention in terms of occupational health. Trust, social network and social
cohesion at the workplace (that is, factors related to social capital) may have
effects on employee health. Thus, the objective of this study was to examine the
association between workplace social capital and mental health among Iranian
workers. METHODS: In this cross-sectional study, data were obtained from 5
factories in Babol, Northern Iran, in 2016, where 280 workers responded to a
survey on social capital at work and psychosocial distress. RESULTS:
Approximately 23.6% of the workers had psychological distress, and 23.4% had low
social capital in the workplace. There was a significant relationship between
mental health and individual workplace social capital (p = 0.025) and aggregated
workplace social capital (p = 0.027). After controlling for each individual's
characteristics, the prevalence ratio of psychological distress was 2.11 (95% CI:
1.43-3.17) times higher among workers with low individual social capital, and low
aggregated workplace social capital was associated with 2.64 (95% CI: 1.28-5.45)
times higher odds of psychological distress. CONCLUSION: Higher social capital is
associated with a reduced risk of psychological distress. The promotion of social
capital can be considered as a means to increase workplace mental health among
workers.
PMID- 29940920
TI - Adverse childhood experiences and sources of childhood resilience: a
retrospective study of their combined relationships with child health and
educational attendance.
AB - BACKGROUND: Adverse childhood experiences (ACEs) including maltreatment and
exposure to household stressors can impact the health of children. Community
factors that provide support, friendship and opportunities for development may
build children's resilience and protect them against some harmful impacts of
ACEs. We examine if a history of ACEs is associated with poor childhood health
and school attendance and the extent to which such outcomes are counteracted by
community resilience assets. METHODS: A national (Wales) cross-sectional
retrospective survey (n = 2452) using a stratified random probability sampling
methodology and including a boost sample (n = 471) of Welsh speakers. Data
collection used face-to-face interviews at participants' places of residence.
Outcome measures were self-reported poor childhood health, specific conditions
(asthma, allergies, headaches, digestive disorders) and school absenteeism.
RESULTS: Prevalence of each common childhood condition, poor childhood health and
school absenteeism increased with number of ACEs reported. Childhood community
resilience assets (being treated fairly, supportive childhood friends, being
given opportunities to use your abilities, access to a trusted adult and having
someone to look up to) were independently linked to better outcomes. In those
with >=4 ACEs the presence of all significant resilience assets (vs none) reduced
adjusted prevalence of poor childhood health from 59.8 to 21.3%. CONCLUSIONS:
Better prevention of ACEs through the combined actions of public services may
reduce levels of common childhood conditions, improve school attendance and help
alleviate pressures on public services. Whilst the eradication of ACEs remains
unlikely, actions to strengthen community resilience assets may partially offset
their immediate harms.
PMID- 29940921
TI - Run4Love, a mHealth (WeChat-based) intervention to improve mental health of
people living with HIV: a randomized controlled trial protocol.
AB - BACKGROUND: People living with HIV (PLWH) suffer from high rates of mental
illness; but targeted effective interventions are limited, especially in
developing countries. High penetration of smartphone usage and widespread
acceptance of social media applications provide an unprecedented opportunity for
mobile-based health interventions (mHealth interventions) in resource-limited
settings like China. The current report describes the design and sample
characteristics of the Run4Love randomized controlled trial (RCT) aimed at
improving mental health in PLWH in China. METHODS: A total of 300 PLWH with
elevated depressive symptoms were recruited and randomized into either the
intervention or control group. Participants in the intervention group received an
adapted cognitive-behavioral stress management (CBSM) course delivered by the
enhanced WeChat platform (for 3 months) and were motivated to engage in physical
activities. Progress of the participants was automatically tracked and monitored
with timely feedback and rewards. The control group received a brochure on
nutrition for PLWH in addition to standard care. The outcome assessments are
conducted at baseline, 3, 6, and 9 months using tablets. The primary outcome is
depressive symptoms measured by the scale of the Center for Epidemiology Studies
Depression (CES-D). Secondary outcomes include quality of life, chronic stress
measured with biomarker of hair cortisol, and other measures of stress and
depression, self-efficacy, coping, HIV-related stigma, physical activity, and
patient satisfaction. Mixed effects model with repeated measures (MMRM) will be
used to analyze the intervention effects. DISCUSSION: The Run4Love study is among
the first efforts to develop and evaluate a multicomponent and integrated mHealth
intervention to improve the mental health and quality of life of PLWH. Once
proven effective, Run4Love could be scaled up and potentially integrated into the
routine case management of PLWH and adapted to other populations with chronic
diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry - ChiCTR-IPR
17012606 , registered on 07 September 2017.
PMID- 29940922
TI - Longitudinal associations between TV viewing and BMI not explained by the
'mindless eating' or 'physical activity displacement' hypotheses among adults.
AB - BACKGROUND: The mechanisms explaining the positive relationship between
television (TV) viewing and body mass index (BMI) are unclear. 'Mindless eating'
and 'physical activity displacement' theories have been suggested, but have not
been tested longitudinally among young adults. This study aimed to determine
whether longitudinal associations between young adults' TV viewing and BMI are
explained by changes in TV-related food and beverage consumption (FBC) and/or
leisure-time physical activity (LTPA) over 5 years among young adults. METHODS: A
cohort of young Australian adults (n = 1068) was assessed in 2004-6 (T1) and 2009
2011 (T2), height and weight were measured (T1) or self-reported (T2), and
participants self-reported TV viewing time (hours/day), weekly TV-related FBC and
LTPA (mins/week). Linear regression was used to examine direct pathways between
TV viewing and BMI, adjusting for TV-related FBC and LTPA to examine indirect
pathways. RESULTS: The association between TV viewing time and BMI (beta: 0.41,
95% CI 0.03, 0.78 for > 1-h increase in TV viewing/day) was not explained by TV
related FBC (beta: 0.37, 95% CI -0.18, 0.91) or LTPA (beta: 0.38, 95% CI -0.17,
0.93) hypotheses. Increased TV-related FBC was associated with increased TV
viewing (0.39 +/- 1.54 h/day) and greater increases in BMI (0.92 +/- 2.28 kg/m2,
p = 0.16). LTPA increases were not associated with changes in TV viewing (- 0.07
+/- 1.42 h/day), and increases in BMI were smallest when LTPA increased (0.44 +/-
2.25 kg/m2) and greatest when LTPA decreased (0.82 +/- 2.30 kg/m2) (p = 0.13).
CONCLUSIONS: Factors other than changes in TV-related FBC or LTPA may explain the
longitudinal relationship between TV viewing and increasing BMI among young
adults. Findings confirm that TV viewing is a risk factor for weight gain in
young adults but the underlying causal mechanisms remain unclear.
PMID- 29940923
TI - Utilising active play interventions to promote physical activity and improve
fundamental movement skills in children: a systematic review and meta-analysis.
AB - BACKGROUND: Children's physical activity levels are low and efforts to improve
their physical activity levels have proven difficult. Freely chosen and
unstructured physical activity (active play) has the potential to be promoted in
a variety of settings and potentially every day of the year in contrast to other
physical activity domains, but active play interventions are an under-researched
area. Therefore, the primary aim of this systematic review was to determine the
effect of active play interventions on children's physical activity levels,
particularly moderate-to-vigorous intensity physical activity (MVPA), and
fundamental movement skills (FMS). METHODS: Studies were included if they were
solely or predominantly active play randomised, or cluster randomised controlled
trials that targeted children aged 3-12 years. They had to report on at least one
of the following outcomes: objectively measured physical activity, FMS, cognition
and weight status. During December 2016, four databases (PE Index, SPORTDiscus,
Medline and ERIC) were searched for relevant titles. Duplicates and irrelevant
titles and abstracts were removed. The included studies had their quality
assessed using the Effective Public Health Practice Project (EPHPP) tool.
Suitable studies were combined in a meta-analysis using a random-effect model. A
narrative synthesis was conducted for all outcomes. RESULTS: Of the 4033 records,
91 studies were eligible for full text screening, of which 87 were removed,
leaving four studies (representing five papers). The meta-analysis of two studies
highlighted there was no significant effect of active play interventions on MVPA.
However, the narrative synthesis suggested that active play interventions may
increase total volume of physical activity. Only two studies examined the effect
of active play interventions on children's FMS, one study examined effects on
weight status and none examined effects on cognition. CONCLUSIONS: Due to the
small number of eligible studies and their heterogeneity, the review could not
draw firm conclusions on the effect of active play interventions on children's
physical activity levels. High-quality active play interventions, targeting
different times of the day (school and after school) in different populations and
settings, and with a wider range of outcomes, are required to determine the
potential of active play.
PMID- 29940924
TI - Community based study to assess the prevalence of diabetic foot syndrome and
associated risk factors among people with diabetes mellitus.
AB - BACKGROUND: Diabetic foot is one of the most significant and devastating
complication of diabetes. The objective of this study was to assess the
prevalence of diabetic foot syndrome (DFS) and the associated risk factors among
people with diabetes mellitus. METHODS: A community based cross-sectional study
was carried out among 620 subjects with diabetes mellitus (DM) in rural areas of
Udupi district. The Michigan Neuropathy Screening Instrument was used to identify
peripheral neuropathy. Ankle brachial index was used to identify peripheral
arterial disease (PAD). Subjects with diabetic foot syndrome were classified
according to the International Working Group on Diabetic Foot (IWGDF)
classification system. RESULTS: The overall prevalence of DFS was 51.8%. Among
them 31.3, 11.9 and 8.5% belonged to category 1, 2 and 3 respectively.
Multivariate logistic regression analysis showed advancing age, low socio
economic status, sedentary physical activity and longer duration of DM were
significant independent correlates of DFS. CONCLUSION: The overall prevalence of
DFS was high among the study population; hence the screening for foot
complications should start at the time of diagnosis of diabetes integrated with
sustainable patient education at primary care level by training of health care
providers at primary care level.
PMID- 29940925
TI - Development of two socioeconomic indices for Saudi Arabia.
AB - BACKGROUND: Health and socioeconomic status (SES) are linked in studies
worldwide. Measures of SES exist for many countries, however not for Saudi Arabia
(SA). We describe two indices of area-based SES for SA. METHODS: Routine census
data has been used to construct two indices of SES at the geographically
delimited administrative region of Governorates in SA (n = 118). The data used
included indicators of educational status, employment status, car and material
ownership. A continuous measure of SES was constructed using exploratory factor
analysis (EFA) and a categorical measure of SES using latent class analysis
(LCA). Both indices were mapped by Governorates. RESULTS: The EFA identified
three factors: The first explained 51.58% of the common variance within the
interrelated factors, the second 15.14%, and the third 14.26%. These proportions
were used in the formulation of the standard index. The scores were fixed to
range from 100 for the affluent Governorate and 0 for the deprived. The LCA found
a 4 class model as the best model fit. Class 1 was termed "affluent" and included
11.01% of Governorates, class 2 "upper middle class" (44.91%), class 3 "lower
middle class" (33.05%) and class 4 "deprived" (11.01%). The populated urbanised
Governorates were found to be the most affluent whereas the smaller rural
Governorates were the most deprived. CONCLUSION: This is the first description of
measures of SES in SA at a geographical level. Two measures have been
successfully constructed and mapped. The maps show similar patterns suggesting
validity. Both indices support the common perception of SES in SA.
PMID- 29940926
TI - Graded motor imagery for women at risk for developing type I CRPS following
closed treatment of distal radius fractures: a randomized comparative
effectiveness trial protocol.
AB - BACKGROUND: Distal radius fractures (DRF) account for nearly one-fifth of all
fractures in older adults, and women experience them 5* as often as men. Most DRF
occur with low impact injuries to the wrist with an outstretched hand, and are
often managed via closed treatment and cast immobilization. Women sustaining a
DRF are at risk for upper limb immobility, sensorimotor changes, edema and type I
complex regional pain syndrome (CRPS). Since CRPS onset is likely influenced by
alterations in the brain's somatosensory region, a rehabilitation intervention,
Graded Motor Imagery (GMI), aims to restore cortical representation, including
sensory and motor function, of the affected limb. To date, there are no studies
on the use of GMI in reducing risk of or preventing the onset of type I CRPS in
women with DRF treated with cast immobilization. Due to a higher likelihood of
women with this injury developing type I CRPS, it is important to early
intervention is needed. METHODS/DESIGN: This article describes a six-week
randomized comparative effectiveness trial, where the outcomes of a modified GMI
program (mGMI) + standard of care (SOC) group (n = 33) are compared to a SOC only
control group (n = 33). Immediately following cast immobilization, both groups
participate in four 1-h clinic-based sessions, and a home program for 10 min
three times daily until cast removal. Blinded assessments occur within 1 week of
cast immobilization (baseline), at three weeks post cast immbolization, cast
removal, and at three months post cast removal. The primary outcomes are patient
reported wrist/hand function and symptomology on the Patient Rated Wristand Hand
Evaluation, McGill Pain Questionnaire, and Budapest CRPS Criteria. The secondary
outcomes are grip strength, active range of motion as per goniometry,
circumferential edema measurements, and joint position sense. DISCUSSION: This
study will investigate the early effects of mGMI + SOC hand therapy compared to
SOC alone. We intend to investigate whether an intervention, specifically mGMI,
used to treat preexisiting pain and motor dysfunction might also be used to
mitigate these problems prior to their onset. If positive effects are observed,
mGMI + SOC may be considered for incorporation into early rehabilitation program.
TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov with
identifier NCT02957240 (Approval date: April 20, 2017).
PMID- 29940927
TI - Identification of research hypotheses and new knowledge from scientific
literature.
AB - BACKGROUND: Text mining (TM) methods have been used extensively to extract
relations and events from the literature. In addition, TM techniques have been
used to extract various types or dimensions of interpretative information, known
as Meta-Knowledge (MK), from the context of relations and events, e.g. negation,
speculation, certainty and knowledge type. However, most existing methods have
focussed on the extraction of individual dimensions of MK, without investigating
how they can be combined to obtain even richer contextual information. In this
paper, we describe a novel, supervised method to extract new MK dimensions that
encode Research Hypotheses (an author's intended knowledge gain) and New
Knowledge (an author's findings). The method incorporates various features,
including a combination of simple MK dimensions. METHODS: We identify previously
explored dimensions and then use a random forest to combine these with linguistic
features into a classification model. To facilitate evaluation of the model, we
have enriched two existing corpora annotated with relations and events, i.e., a
subset of the GENIA-MK corpus and the EU-ADR corpus, by adding attributes to
encode whether each relation or event corresponds to Research Hypothesis or New
Knowledge. In the GENIA-MK corpus, these new attributes complement simpler MK
dimensions that had previously been annotated. RESULTS: We show that our approach
is able to assign different types of MK dimensions to relations and events with a
high degree of accuracy. Firstly, our method is able to improve upon the
previously reported state of the art performance for an existing dimension, i.e.,
Knowledge Type. Secondly, we also demonstrate high F1-score in predicting the new
dimensions of Research Hypothesis (GENIA: 0.914, EU-ADR 0.802) and New Knowledge
(GENIA: 0.829, EU-ADR 0.836). CONCLUSION: We have presented a novel approach for
predicting New Knowledge and Research Hypothesis, which combines simple MK
dimensions to achieve high F1-scores. The extraction of such information is
valuable for a number of practical TM applications.
PMID- 29940928
TI - Patient centred care for the medical treatment of lower urinary tract symptoms in
patients with benign prostatic obstruction: a key point to improve patients' care
- a systematic review.
AB - BACKGROUND: Even though evidence based medicine, guidelines and algorithms still
represent the pillars of the management of chronic diseases (i.e: hypertension,
diabetes mellitus), a patient centred approach has been recently proposed as a
successful strategy, in particular to improve drug adherence. Aim of the present
review is to evaluate the unmet needs in LUTS/BPH management and the possible
impact of a patient centered approach in this setting. METHODS: A National Center
for Biotechnology Information (NCBI) PubMed search for relevant articles
published from January 2000 until December 2016 was performed by combining the
following MESH terms: patients centred medicine, patient centered care, person
centered care, patient centered outcomes, value based care, shared decision
making, male, Lower Urinary Tract Symptoms, Benign Prostatic Hyperplasia,
treatment. We followed the Preferred Reporting Items for Systematic Review and
Meta-Analysis (PRISMA). All studies reporting on patient centred approach, shared
decision making and evidence-based medicine were included in the review. All
original article, reviews, letters, congress abstracts, and editorials comments
were included in the review. Studies reporting single case reports, experimental
studies on animal models and studies not in English were not included in the
review. RESULTS: Overall 751 abstracts were reviewed, out of them 87 full texts
were analysed resulting in 36 papers included. The evidence summarised in this
systematic review confirmed how a patient centred visit may improve patient's
adherence to medication. Although a patient centred model has been rarely used in
urology, management of Low Urinary Tract Symptoms (LUTS) and Benign Prostatic
Obstruction (BPO) may represent the perfect ground to experiment and improve this
approach. Notwithstanding all the innovations in LUTS/BPO medical treatment, the
real life picture is far from ideal. CONCLUSIONS: Recent evidence shows a
dramatical low drug adherence and satisfaction to medical treatment in LUTS/BPH
patients. A patient centred approach may improve drug adherence and some unmet
needs in this area, potentially reducing complications and costs. However further
well designed studies are needed to confirm this data.
PMID- 29940929
TI - The potential of Olea europaea extracts to prevent TGFbeta1-induced epithelial to
mesenchymal transition in human nasal respiratory epithelial cells.
AB - BACKGROUND: One of the molecular mechanisms involved in upper airway-related
diseases is epithelial-to-mesenchymal transition (EMT). Olea europaea (OE) has
anti-inflammatory properties and thus, great potential to prevent EMT. This study
aimed to investigate the effect of OE on EMT in primary nasal human respiratory
epithelial cells (RECs). METHODS: Respiratory epithelial cells were isolated and
divided into four groups: control (untreated), treated with 0.05% OE (OE group),
EMT induced with 5 ng/ml of transforming growth factor beta-1 (TGFbeta1 group)
and treated with 5 ng/ml TGFbeta1 + 0.05% OE (TGFbeta1 + OE group). The effects
of OE treatment on growth kinetics, morphology and protein expression in RECs
were evaluated. Immunocytochemistry analysis was performed to quantitate the
total percentage of E-cadherin and vimentin expression from day 1 to day 3.
RESULTS: There were no significant differences between untreated RECs and OE
treated RECs in terms of their morphology, growth kinetics and protein
expression. Induction with TGFbeta1 caused RECs to have an elongated spindle
shape, a slower proliferation rate, a higher expression of vimentin and a lower
expression of E-cadherin compared with the control. Cells in the TGFbeta1 + OE
group had similar epithelial shape to untreated group however it had no
significant differences in their proliferation rate when compared to TGFbeta1
induced RECs. Cells treated with TGFbeta1 + OE showed significantly reduced
expression of vimentin and increased expression of E-cadherin compared with the
TGFbeta1 group (P < 0.05). CONCLUSION: The ability of OE to inhibit EMT in RECs
was shown by TGFb1-induced EMT REC morphology, growth kinetics and protein
expression markers (E-cadherin and vimentin) upon treatment with OE and TGFbeta1.
Therefore, this study could provide insight into the therapeutic potential of OE
to inhibit pathological tissue remodelling and persistent inflammation.
PMID- 29940930
TI - Complete genomic characteristics and pathogenic analysis of the newly emerged
classical swine fever virus in China.
AB - BACKGROUND: Classical swine fever (CSF) is one of the most devastating and highly
contagious viral diseases in the world. Since late 2014, outbreaks of a new sub
genotype 2.1d CSF virus (CSFV) had caused substantial economic losses in numbers
of C-strain vaccinated swine farms in China. The objective of the present study
was to explore the genomic characteristics and pathogenicity of the newly emerged
CSFV isolates in China during 2014-2015. RESULTS: All the new 8 CSFV isolates
belonged to genetic sub-genotype 2.1d. Some genomic variations or deletions were
found in the UTRs and E2 of these new isolates. In addition, the pathogenicity of
HLJ1 was less than Shimen, suggesting the HLJ1 of sub-genotype 2.1d may be a
moderated pathogenic isolate and the C-strain vaccine can supply complete
protection. CONCLUSIONS: The new CSFV isolates with unique genomic
characteristics and moderate pathogenicity can be epidemic in many large-scale C
strain vaccinated swine farms. This study provides the information should be
merited special attention on establishing prevention and control policies for
CSF.
PMID- 29940931
TI - Health care provision for refugees in Germany - one-year evaluation of an
outpatient clinic in an urban emergency accommodation.
AB - BACKGROUND: In 2015, Germany recorded the highest rates of refugees since the
early 1990s. Access to medical care is a legally regulated fundamental element of
aid for refugees. In practice, there are several hurdles such as language
barriers and legal regulations. In response to the massively increased need,
special outpatient services for refugees were started in several German cities.
In Cologne, an outpatient clinic (OPD) was established in the largest emergency
accommodation centre for refugees supported by the Cologne municipality and
operated by the German Red Cross and physicians from the Association of Statutory
Health Insurance Physicians. This study reports experiences of the first year of
the OPD regarding structure, processes and utilization. METHODS: Employing mixed
methods, between May and December 2015 cross sectional pseudonymized data from
patients' contacts were collected, coded in the International Classification of
Primary Care (ICPC) and evaluated. Infrastructure, equipment, process
organisation and function of the OPD were assessed during five participatory
observations and triangulated with results of a self-administered questionnaire
for staff and four qualitative interviews with key informants. RESULTS: During
the observation period a total of 2205 persons (67% male) stayed in the emergency
accommodation and 984 patient contacts (51% male) were registered, mainly by
young persons from Western Balkan countries and Syria. Medical treatment was
sought primarily for acute respiratory-, loco-motor-system- and skin symptoms
followed by chronic physical diseases. Headache, back and neck pain and acute
respiratory infection were the most frequent diagnoses. Questionnaires and
interviews among staff revealed language barriers and psycho-trauma as the most
frequently reported challenges. Equipment and staffing was adequate, but patient
documentation was not systematic, leading to loss of information. CONCLUSION: To
facilitate refugees' appropriate access to health care, the OPD was seen as
functional for this refugee accommodation centre. Need was recognised for
standardized, data protective documentation and a health passport for clients for
medical information. Psychological support for refugees needs expansion taking
legal circumstances and coverage of costs into consideration. To improve patient
communication employees working with refugees should be offered an introduction
to culturally sensitive understanding of health and illness.
PMID- 29940932
TI - Changes in pulmonary endothelial cell properties during bleomycin-induced
pulmonary fibrosis.
AB - BACKGROUND: Pulmonary fibrosis is a progressive and lethal disease characterized
by damage to the lung parenchyma with excess extracellular matrix deposition. The
involvement of endothelial cells in fibrosis development is unclear. METHODS: We
isolated pulmonary endothelial cells, using a magnetic-activated cell sorting
system, from mice with pulmonary fibrosis induced by intratracheal bleomycin. We
characterized endothelial cells isolated at various times in the course of
pulmonary fibrosis development. RESULTS: Inflammatory cell infiltration was
observed at 7 days after bleomycin administration, and fibrotic changes with
increased collagen content were observed on day 21. Endothelial cells were
isolated at these two timepoints. Levels of von Willebrand factor, plasminogen
activator inhibitor-1 and matrix metalloproteinase-12 were elevated in lung
endothelial cells isolated from bleomycin-treated mice at days 7 and 21. This
indicated that intratracheal bleomycin administration induced endothelium injury.
Expression of fibrogenic mediators, transforming growth factor (TGF)-beta,
connective tissue growth factor and platelet-derived growth factor-C was elevated
in the cells from bleomycin-treated, compared with untreated, lungs. When
endothelial cells were treated with TGF-beta, alpha-smooth muscle actin (SMA)
expression and collagen production were increased only in those cells from
bleomycin-treated mouse lungs. Thapsigargin-induced prostaglandin I2 and nitric
oxide production, decreased in endothelial cells from bleomycin-treated mouse
lungs, compared with controls, was further suppressed by TGF-beta. CONCLUSION:
Bleomycin administration induced functional changes in lung endothelial cells,
indicating potential involvement of endothelium in pulmonary fibrogenesis.
PMID- 29940934
TI - Frequent attenders at primary care out-of-hours services: a registry-based
observational study in Norway.
AB - BACKGROUND: Out-of-hours (OOH) services are often consulted for problems that are
non-urgent. Some of these patients are frequent attenders (FAs) who may
constitute a heavy burden on the OOH service. The aim of the present study was to
analyse FAs in a comprehensive material, covering all patients who have visited
OOH services in Norway during a 10-year period. METHODS: FA was defined as a
patient having >=5 consultations during one year. A cohort of all 15,172 FAs in
2008 was followed until 2017, with a description of demographics, consultations,
and diagnoses for each year. FAs in 2017 were also analysed with more extreme
definitions (>=10, >=20, >=30 consultations). To analyse predictors for FA a
logistic regression analysis was performed on the 2017 data. RESULTS: FAs
constituted 2% of all patients (U-shaped age curve and female overrepresentation)
and approximately 10% of all consultations each year. 59.8% of the cohort was
never FA again, 17.7% had one relapse, 8.6% two, and 4.4% had three relapses.
22.8% was also a FA in 2009. Thereafter the percentage gradually declined to 6.2%
in 2017. Only 0.8% of the original cohort were persistent FAs throughout the 10
year period. FAs were three times as likely to be given a psychological diagnosis
as the average OOH patient, and this percentage increased in persistent and more
extreme FAs. FAs tended to seek help at inconvenient hours (late evening and
night), and increasingly so the more extreme they were. Also, they needed more
consultation time and more often received home visits. The logistic regression
analysis identified the following predictors for becoming FA (odds ratio = OR):
Female (OR 1.17), age 0-1 years (OR 3.46), age 70+ (OR 1.57), small municipality
(OR 1.61), psychological diagnosis (OR 10.00), social diagnosis (OR 5.97), cancer
(OR 6.76), diabetes (OR 4.65), and chronic obstructive pulmonary disease (OR
7.81). CONCLUSIONS: FAs were most common among the youngest children and among
the elderly, increasing with age. Females were overrepresented, as were patients
with psychosocial problems and various chronic somatic conditions. The majority
were only temporary FAs.
PMID- 29940933
TI - The effect of mirabegron, used for overactive bladder treatment, on female sexual
function: a prospective controlled study.
AB - BACKGROUND: Alphaim of the study was to determine the effect of mirabegron, used
for overactive bladder (OAB) treatment, on female sexual function. METHODS:
Eighty five sexually active women suffering from overactive bladder were
prospectively enrolled in this study. Females were divided into two groups. In
Group A (control), 48 patients received no treatment and in Group B, 37 patients
received mirabegron 50 mg/daily for 3 months. Patients were evaluated with FSFI
Gr at the beginning of the study and again after a period of 3 months. RESULTS:
In Group B, there was a significant increase post-treatment compared to baseline
(p < 0.001) in total FSFI (20.3 (3.8) to 26.6 (4.2)) and all domains (desire: 3.0
(1.2) to 4.8 (1.2)), arousal: 3.0 (0.8) to 4.8 (0.9), lubrication: 3.9 (1.1) to
4.8 (1.2), orgasm: 3.6 (0.8) to 4.8 (1.0), satisfaction: 3.2 (0.4) to 4.0 (0.8)
and pain: 3.2 (0.8) to 4.4 (1.2)). In Group A, there were no statistically
significant changes in pre- and post-observation values. CONCLUSIONS: This study
is one of the few demonstrating that management of OAB with mirabegron improves
female sexual function. TRIAL REGISTRATION: TRN ISRCTN17199301 , 20/10/2017,
retrospectively registered.
PMID- 29940935
TI - Coconut water vinegar ameliorates recovery of acetaminophen induced liver damage
in mice.
AB - BACKGROUND: Coconut water has been commonly consumed as a beverage for its
multiple health benefits while vinegar has been used as common seasoning and a
traditional Chinese medicine. The present study investigates the potential of
coconut water vinegar in promoting recovery on acetaminophen induced liver
damage. METHODS: Mice were injected with 250 mg/kg body weight acetaminophen for
7 days and were treated with distilled water (untreated), Silybin (positive
control) and coconut water vinegar (0.08 mL/kg and 2 mL/kg body weight). Level of
oxidation stress and inflammation among treated and untreated mice were compared.
RESULTS: Untreated mice oral administrated with acetaminophen were observed with
elevation of serum liver profiles, liver histological changes, high level of
cytochrome P450 2E1, reduced level of liver antioxidant and increased level of
inflammatory related markers indicating liver damage. On the other hand,
acetaminophen challenged mice treated with 14 days of coconut water vinegar were
recorded with reduction of serum liver profiles, improved liver histology,
restored liver antioxidant, reduction of liver inflammation and decreased level
of liver cytochrome P450 2E1 in dosage dependent level. CONCLUSION: Coconut water
vinegar has helped to attenuate acetaminophen-induced liver damage by restoring
antioxidant activity and suppression of inflammation.
PMID- 29940936
TI - The impact of telehealth remote patient monitoring on glycemic control in type 2
diabetes: a systematic review and meta-analysis of systematic reviews of
randomised controlled trials.
AB - BACKGROUND: There is a growing body of evidence to support the use of telehealth
in monitoring HbA1c levels in people living with type 2 diabetes. However, the
overall magnitude of effect is yet unclear due to variable results reported in
existing systematic reviews. The objective of this study is to conduct a
systematic review and meta-analysis of systematic reviews of randomised
controlled trials to create an evidence-base for the effectiveness of telehealth
interventions on glycemic control in adults with type 2 diabetes. METHODS:
Electronic databases including The Cochrane Library, MEDLINE, EMBASE, HMIC, and
PsychINFO were searched to identify relevant systematic reviews published between
1990 and April 2016, supplemented by references search from the relevant reviews.
Two independent reviewers selected and reviewed the eligible studies. Of the 3279
references retrieved, 4 systematic reviews reporting in total 29 unique studies
relevant to our review were included. Both conventional pairwise meta-analyses
and network meta-analyses were performed. RESULTS: Evidence from pooling four
systematic reviews found that telehealth interventions produced a small but
significant improvement in HbA1c levels compared with usual care (MD: -0.55, 95%
CI: -0.73 to - 0.36). The greatest effect was seen in telephone-delivered
interventions, followed by Internet blood glucose monitoring system interventions
and lastly interventions involving automatic transmission of SMBG using a mobile
phone or a telehealth unit. CONCLUSION: Current evidence suggests that telehealth
is effective in controlling HbA1c levels in people living with type 2 diabetes.
However there is need for better quality primary studies as well as systematic
reviews of RCTs in order to confidently conclude on the impact of telehealth on
glycemic control in type 2 diabetes.
PMID- 29940937
TI - Probiotic fermentation augments the skin anti-photoaging properties of Agastache
rugosa through up-regulating antioxidant components in UV-B-irradiated HaCaT
keratinocytes.
AB - BACKGROUND: Agastache rugosa (Fisch. & C.A.Mey.) Kuntze (Korean mint) is used to
treat diverse types of human disorders in traditional medicine. In recent years,
its non-fermented leaf extract (ARE) has been shown to possess protective
properties against ultraviolet-B (UV-B) radiation-induced photooxidative stress.
The present work aimed to examine whether probiotic bacterial fermentation would
potentiate the skin anti-photoaging activity of ARE or not, by comparing the
protective properties of ARE and corresponding fermented extract (ARE-F) against
UV-B radiation-induced photooxidative stress in HaCaT keratinocytes. METHODS: ARE
F was produced from ARE by the fermentation with Lactobacillus rhamnosus HK-9, a
type of Gram-positive probiotic bacterial strain. Anti-photoaging activities were
evaluated by analyzing reactive oxygen species (ROS), promatrix
metalloproteinases (proMMPs), total glutathione (GSH) and total superoxide
dismutase (SOD) in UV-B-irradiated HaCaT keratinocytes. Antiradical activity was
determined using 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)
radical scavenging assay. RESULTS: ARE-F contained higher attenuating activity on
the UV-B-induced ROS generation than ARE. Similarly, ARE-F was able to diminish
the UV-B-induced proMMP-9 and -2 more effectively than ARE. ARE-F displayed
higher tendencies to augment the UV-B-reduced total GSH content and SOD activity
than ARE. However, there were no significant difference between ARE and ARE-F in
ABTS radical scavenging activities. CONCLUSIONS: The findings suggest that the UV
B radiation-protective activity of ARE is enhanced by probiotic bacterial
fermentation, which might improve the therapeutic and cosmetic values of A.
rugosa leaves.
PMID- 29940938
TI - Recombinant E2 protein enhances protective efficacy of inactivated bovine viral
diarrhea virus 2 vaccine in a goat model.
AB - BACKGROUND: Inactivated and subunit bovine viral diarrhea virus (BVDV) vaccines
have shown limited protective efficacy. This study aimed to evaluate the
effectiveness of a vaccine containing both inactivated BVDV (iBVDV) and
baculovirus-expressed recombinant E2 (rE2), an important BVDV antigen with
strongly neutralizing epitopes. RESULTS: Four groups of goats were immunized
twice with one of four vaccine preparations: 1) iBVDV+rE2, 2) rE2, 3) iBVDV, and
4) saline, and challenged with BVDV. For goats vaccinated with the iBVDV+rE2
vaccine, no viremia was observed after challenge, and clinical signs, pyrexia,
and leukopenia were reduced compared to the saline group. In contrast, for goats
vaccinated with either iBVDV or rE2 alone, viremia was still detectable.
CONCLUSION: The combination of iBVDV and rE2 elicited stronger protective immune
responses against BVDV than iBVDV or rE2 alone.
PMID- 29940939
TI - Seroprevalence and risk factors of recent infection with hepatitis E virus during
an acute outbreak in an urban setting in Chad, 2017.
AB - BACKGROUND: From September 2016-April 2017, Am Timan, Chad, experienced a large
HEV outbreak in an urban setting with a limited impact in terms of morbidity and
mortality. To better understand HEV epidemiology in this context, we estimated
the seroprevalence of anti-HEV antibodies (IgM and IgG) and assessed the risk
factors for recent HEV infections (positive anti-HEV IgM) during this outbreak.
METHODS: A serological survey using simple random sampling was implemented in Am
Timan at the tail-end of the outbreak (sample size aim = 384 household).
Household members provided us with blood samples and household heads answered
questions around water, sanitation and hygiene practices and animal ownership.
Blood samples were tested for HEV IgG and IgM antibodies using Enzyme-Immune
Assay (EIA). We calculated weighted prevalence estimates and prevalence ratios
(PRs) for possible risk factors for recent infection using multivariate Cox
regression. RESULTS: We included 241 households (1529 participants). IgM
prevalence decreased with age: 12.6% (< 5 years) to 4.3% (> 15 years). IgG
prevalence increased with age: 23.5% (< 5 years) to 75.9% (> 15 years). Risk
factors for recent HEV infections included: sharing the sanitation facility with
other HHs (PR 1.72; 95%CI: 1.08-2.73), not systematically using soap for HW (PR
1.85; 95%CI: 1.30-2.63) and having animals sleeping inside the compound (PR 1.69;
95%CI: 1.15-2.50). CONCLUSIONS: Evidence suggests that Am Timan was already
highly endemic for HEV before the outbreak, potentially explaining the limited
extent of the outbreak. Recent infection with HEV was linked to household level
exposures. Future HEV outbreak response must include ensuring access to safe
water, and reducing household level transmission through active hygiene and
sanitation promotion activities.
PMID- 29940940
TI - First report on cutaneous infectious granuloma caused by Schizophyllum commune.
AB - BACKGROUND: Schizophyllum commune, a basidiomycetous fungus, is a common invader
of rotten wood. This fungus rarely causes mycotic disease in humans, especially
cutaneous infection. In this paper, we describe the first case of cutaneous
granuloma caused by S. commune in a Chinese woman. CASE PRESENTATION: A 25-year
old female with a two-year history of erythema, papules, nodules, and scales on
her sole of left foot was presented to our outpatient center. Samples were
obtained by the scraping of lesion and for light microscopy. Hyphae were observed
by microscopic examination. We carried out a skin tissue biopsy, which showed
multiple granulomatous nodules. Biopsy specimens were also inoculated onto media.
After being cultured on SDA at 27 degrees C for 7 days, spreading-woolly-white
colonies grew on the inoculation sites of media containing chloramphenicol only
and there,s no other colonies grew. S. commune was identified by morphology
methods, biochemical tests, and PCR sequencing. Pathological findings also aided
in diagnosing cutaneous fungal granuloma. Oral itraconazole was applied. After 1
month of therapy, rashes on her left foot and pain were improved. CONCLUSION: We
describe the first case of cutaneous granuloma caused by Schizophyllum commune,
which illustrates the importance of recognizing uncommon pathogenic fungal
infections.
PMID- 29940941
TI - Evaluating quality neonatal care, call Centre service, tele-health and community
engagement in reducing newborn morbidity and mortality in Bungoma county, Kenya.
AB - BACKGROUND: Neonatal mortality is a major health burden in Bungoma County with
the rate estimated at 31 per 1000 live births and is above the national average
of 22 per 1000. Nonetheless, out of the nine sub county hospitals, only two are
fairly equipped with necessary infrastructure and skilled personnel to manage
neonatal complications such as prematurity, neonatal sepsis, neonatal jaundice,
birth asphyxia and respiratory distress syndrome. Additionally, with more than
50% of neonates delivered without skilled attendance, in below par hygiene
environments such as home and on the roadsides, with non-existent community based
referral system, the situation is made worse. The study aims to evaluate the
progress made by an intervention "Collaborative Newborn Support Project" geared
towards reducing neonatal mortality rate by 30% between October 2015 and December
2018 in Bungoma County, Kenya. METHODS/DESIGN: This intervention will take a
quasi-experimental design approach with experimental and control sites. The
project will involve pre- and post-intervention data collection with comparison
group to assess intervention effects. The primary outcome will be the percentage
reduction of neonatal mortality in Bungoma County. Secondary outcomes include; a)
Percentage of mothers or care givers able to identify at least three danger signs
in neonates in the project area, b) Proportion of neonates with complications
referred to specialized neonatal centers, through the call center, c) Percentage
of health providers in neonatal care units who adhere to expected neonatal
standards of care (rapid and complete application of standard protocols), d)
Percentage increase in neonates with severe complications in the specialized
neonatal units and e) Percentage of neonates who stay in neonatal care units
beyond 5 days. DISCUSSION: We outline implementation details of the ongoing
'Collaborative Newborn Support Project' in Bungoma County, Kenya. This includes
strategies in the operations of the telehealth platform, call centre service,
community engagement and measuring of the outputs and outcomes. The funding and
ethical approvals have been obtained and the study commenced. TRIAL REGISTRATION:
PACTR201712002802638 Retrospectively registered on 5th December 2017 at Pan
African Clinical Trials Registry.
PMID- 29940942
TI - Symptoms awareness, emergency medical service utilization and hospital transfer
delay in myocardial infarction.
AB - BACKGROUND: The length of time between symptom onset and reperfusion therapy in
patients with ST-segment elevation acute myocardial infarction (STEMI) is a key
determinant of mortality. Information on this delay is scarce, particularly for
developing countries. The objective of the study is to prospectively evaluate the
individual components of reperfusion time (RT) in patients with STEMI treated at
a University Hospital in 2012. METHODS: Medical records were reviewed to
determine RT, its main (patient delay time [PDT] and system delay time [SDT]) and
secondary components and hospital access variables. Cognitive responses were
evaluated using a semi-structured questionnaire. RESULTS: A total of 50 patients
with a mean age of 59 years (SD = 10.5) were included, 64% of whom were male. The
median RT was 430 min, with an interquartile range of 315-750 min. Regarding the
composition of RT in the sample, PDT corresponded to 18.9% and SDT to 81.1%.
Emergency medical services were used in 23.5% of cases. Patients treated in
intermediate care units showed a significant increase in SDT (p = 0.008).
Regarding cognitive variables, PDT was approximately 40 min longer among those
who answered "I didn't think it was serious" (p = 0.024). CONCLUSIONS: In a
Brazilian tertiary public hospital, RT was higher than that recommended by
international guidelines, mainly because of long SDT, which was negatively
affected by time spent in intermediate care units. Emergency Medical Services
underutilization was noted. A patient's low perception of severity increased PDT.
PMID- 29940943
TI - Otitis in a cat associated with Corynebacterium provencense.
AB - BACKGROUND: The role of corynebacteria in canine and feline otitis has not been
investigated in detail; however, members of this genus are increasingly
recognized as pathogens of otitis in both human and veterinary medicine. CASE
PRESENTATION: Here we report the first case of feline otitis associated with the
recently described species Corynebacterium provencense. A seven-month old cat
presented with a head tilt and ataxia was diagnosed with peripheral vestibular
syndrome associated with an otitis media/interna. This took place 6 weeks after
resection of a polyp, having initially shown a full recovery with topical
ofloxacin and glucocorticoid treatment. Bacteriology of an ear swab yielded a
pure culture of corynebacteria, which could not be identified at the species
level using routine methods. However, the 16S rRNA gene sequence was 100%
identical to the recently published novel corynebacterium species,
Corynebacterium provencense. Whole genome sequencing of the cat isolate and
calculation of average nucleotide identity (99.1%) confirmed this finding. The
cat isolate was found to contain additional presumptive iron acquisition genes
that are likely to encode virulence factors. Furthermore, the strain tested
resistant to clindamycin, penicillin and ciprofloxacin. The cat was subsequently
treated with chloramphenicol, which lead to clinical improvement. CONCLUSION:
Corynebacteria from otitis cases are not routinely identified at the species
level and not tested for antimicrobial susceptibility in veterinary laboratories,
as they are not considered major pathogens. This may lead to underreporting of
this genus or animals being treated with inappropriate antimicrobials since
corynebacteria are often resistant to multiple drugs.
PMID- 29940945
TI - Pulmonary arterial hypertension in Latin America: epidemiological data from local
studies.
AB - BACKGROUND: Pulmonary arterial hypertension is a rare, progressive disease with
poor prognosis. However, there is limited information available on the
characteristics of PAH patients outside of North America and Europe. This is
particularly important as researchers have described that there are potential
geographical and regional differences which are vital to consider in the design
of clinical trials as well as PAH treatment. The aim of this study was to
describe the epidemiology of PAH (PH group 1) in Latin America. METHODS: A search
of electronic databases for studies published in English, Spanish or Portuguese
was conducted specifying publication dates from the 1st of January 1987 until
10th October 2016. Two authors independently assessed papers for inclusion and
extracted data. A narrative synthesis of the findings was conducted. RESULTS: The
search revealed 22 conference abstracts and articles, and on application of the
inclusion criteria, six conference abstracts and articles were included in the
final review. Studies/registries were based in Argentina, Brazil and Chile. In
contrast to the available literature from developed countries, in Latin America,
most patients were diagnosed at younger age; nevertheless, the higher prevalence
of idiopathic PAH (IPAH) and the advanced stage of the disease at diagnosis were
comparable to the existing literature, as the long term survival, despite the
lower availability of targeted therapies. CONCLUSION: This study highlights the
regional characteristics in the epidemiology of group 1 PH. The recognition of
these differences should be considered when developing clinical guidelines and
extrapolating diagnostic and treatment algorithms. Equitable access to health
care and therapies are also issues that need to be addressed in Latin America.
Information coming from a large prospective registry representing the different
populations in Latin America is of critical importance to increase disease
awareness in the region and improve diagnosis and management.
PMID- 29940944
TI - Structure and dynamics of a human myelin protein P2 portal region mutant indicate
opening of the beta barrel in fatty acid binding proteins.
AB - BACKGROUND: Myelin is a multilayered proteolipid sheath wrapped around selected
axons in the nervous system. Its constituent proteins play major roles in forming
of the highly regular membrane structure. P2 is a myelin-specific protein of the
fatty acid binding protein (FABP) superfamily, which is able to stack lipid
bilayers together, and it is a target for mutations in the human inherited
neuropathy Charcot-Marie-Tooth disease. A conserved residue that has been
proposed to participate in membrane and fatty acid binding and conformational
changes in FABPs is Phe57. This residue is thought to be a gatekeeper for the
opening of the portal region upon ligand entry and egress. RESULTS: We performed
a structural characterization of the F57A mutant of human P2. The mutant protein
was crystallized in three crystal forms, all of which showed changes in the
portal region and helix alpha2. In addition, the behaviour of the mutant protein
upon lipid bilayer binding suggested more unfolding than previously observed for
wild-type P2. On the other hand, membrane binding rendered F57A heat-stable,
similarly to wild-type P2. Atomistic molecular dynamics simulations showed
opening of the side of the discontinuous beta barrel, giving important
indications on the mechanism of portal region opening and ligand entry into
FABPs. The results suggest a central role for Phe57 in regulating the opening of
the portal region in human P2 and other FABPs, and the F57A mutation disturbs
dynamic cross-correlation networks in the portal region of P2. CONCLUSIONS:
Overall, the F57A variant presents similar properties to the P2 patient mutations
recently linked to Charcot-Marie-Tooth disease. Our results identify Phe57 as a
residue regulating conformational changes that may accompany membrane surface
binding and ligand exchange in P2 and other FABPs.
PMID- 29940946
TI - How U.S. children's hospitals define population health: a qualitative, interview
based study.
AB - BACKGROUND: The literature suggests that although adult hospitals are
establishing population health programs around the country, there is considerable
definitional ambiguity regarding whether interventions are aimed at the social
determinants of health or the management of existing patient populations. U.S.
children's hospitals also undertake population health programs, but less is known
about how they define population health. The purpose of this study is to
understand how U.S. children's hospitals define population health, and how
institutions are adjusting to new preventive health care models. METHODS: We
conducted semi-structured interviews with key stakeholders at ten hospitals with
the highest amount of staff time dedicated to population health activities as
reported in the 2016 Children's Hospital Association's population health survey.
Using a semi-structured interview guide, we interviewed representatives from each
hospital. Verbatim interview notes were coded and analyzed using the data
analysis software Dedoose. Data analysis followed a modified constructivist
grounded theory approach. RESULTS: Our results suggest that even population
health innovators employ a variety of approaches that span both population health
management and public health. We present further evidence that U.S. children's
hospitals are actively debating the definition and focus of population health.
CONCLUSIONS: Definitional debates are ongoing even within children's hospitals
that are dedicating significant resources to population health. Increased clarity
on the conceptual boundaries between population health and population health
management could help preserve the theoretical differences between the two
concepts, especially insofar as they mark two quite different long-term visions
for health care. Without agreement about the meaning of population health within
and among institutions, hospitals will not be able to know whether projects aimed
at addressing the social determinants of health are likely to improve the health
of populations.
PMID- 29940947
TI - Gynaecologists' and general surgeons' preference for the features of integrated
theatres: a discrete choice experiment.
AB - BACKGROUND: Laparoscopic surgery is progressing rapidly is becoming the normal
route for many abdominal operations, even for major complex surgery. The
integrated laparoscopic theatre is a state-of-the-art system in which the
laparoscopic equipment and multiple flat-screen monitors are permanently
installed to be operational on demand inside the theatre. These expensive systems
are being widely adopted, however very little research has been published
regarding which features of these systems are desired by the surgeons who use
them. The study objective was to assess the strength of preference for key
attributes of integrated laparoscopic theatres and to compare these preferences
between Gynaecologists and General surgeons. METHODS: This was an electronically
distributed discrete choice experiment survey of British practicing Laparoscopic
Gynaecologists and General Surgeons (Through The British Society of Gynaecology
Endoscopy and The Association of Laparoscopic Surgeons of Great Britain and
Ireland). An electronic survey was designed and pre-tested. This was then sent to
practicing British Laparoscopic Gynaecologists and General-Surgeons. There were
structured questions regarding the seven key attributes of integrated
laparoscopic theatres in the standard form for a discrete choice experiment.
RESULTS: Questionnaires from 167 respondents were analysed. One hundred three
were gynaecologists and 64 were general-surgeons. Adjustable screens for height
and position was the most favoured attribute and it is 4.7 times more desirable
than the next most desirable attribute, which was a wire free floor. The least
desirable features were piped CO2, ceiling-mounted-screens and external
transmission-of-images. CONCLUSION: Both groups favour adjustable screens for
position and height above all the other features. These findings are in contrast
with previous research, which showed that when asked to rank the attributes in
order, gynaecologists chose ceiling mounted screens first and adjustable screens
fourth. When asked to "trade off" attributes in the discrete choice experiment
the adjustability of the screens became much more important than how the screens
were mounted. With new wireless technology the benefits of a fully integrated
theatre could be delivered with floor mounted systems at a considerably reduced
cost. This information is important to manufacturers and purchasers of these
systems in order to design cost effective ergonomic theatres that are fit for
purpose.
PMID- 29940948
TI - "It happens to clinicians too": an Australian prevalence study of intimate
partner and family violence against health professionals.
AB - BACKGROUND: The purpose of this study was to measure the prevalence of intimate
partner and family violence amongst a population of Australian female nurses,
doctors and allied health professionals. METHODS: We conducted a descriptive,
cross-sectional survey in a large Australian tertiary maternity hospital with 471
participating female health professionals (45.0% response rate). The primary
outcome measures were 12 month and lifetime prevalence of intimate partner
violence (Composite Abuse Scale) and family violence. RESULTS: In the last 12
months, one in ten (43, 11.5%) participants reported intimate partner violence:
4.2% (16) combined physical, emotional and/or sexual abuse; 6.7% (25) emotional
abuse and/or harassment; 5.1% (22) were afraid of their partner; and 1.7% (7) had
been raped by their partner. Since the age of sixteen, one third (125, 29.7%) of
participants reported intimate partner violence: 18.3% (77) had experienced
combined physical, emotional and/or sexual abuse; 8.1% (34) emotional abuse
and/or harassment; 25.6% (111) had been afraid of their partner; and 12.1% (51)
had been raped by their partner. Overall, 45.2% (212) of participants reported
violence by a partner and/or family member during their lifetime, with 12.8% (60)
reporting both. CONCLUSION: Intimate partner and family violence may be common
traumas in the lives of female health professionals, and this should be
considered in health workplace policies and protocols, as health professionals
are increasingly urged to work with patients who have experienced intimate
partner and family violence. Implications include the need for workplace manager
training, special leave provision, counselling services and other resources for
staff.
PMID- 29940949
TI - Individual and organizational predictors of allied healthcare providers' job
satisfaction in residential long-term care.
AB - BACKGROUND: Job satisfaction is a predictor of intention to stay and turnover
among allied healthcare providers. However, there is limited research examining
job satisfaction among allied health professionals, specifically in residential
long-term care (LTC) settings. The purpose of this study was to identify factors
(demographic, individual, and organizational) that predict job satisfaction among
allied healthcare providers in residential LTC. METHODS: We conducted a secondary
analysis of data from Phase 2 of the Translating Research in Elder Care program.
A total of 334 allied healthcare providers from 77 residential LTC in three
Western Canadian provinces were included in the analysis. Generalized estimating
equation modeling was used to assess demographics, individual, and organizational
context predictors of allied healthcare providers' job satisfaction. We measured
job satisfaction using the Michigan Organizational Assessment Questionnaire Job
Satisfaction Subscale. RESULTS: Both individual and organizational context
variables predicted job satisfaction among allied healthcare providers employed
in LTC. Demographic variables did not predict job satisfaction. At the individual
level, burnout (cynicism) (beta = -.113, p = .001) and the competence subscale of
psychological empowerment (beta = -.224, p = < .001), were predictive of lower
job satisfaction levels while higher scores on the meaning (beta = .232, p =
.001), self-determination (beta = .128, p = .005), and impact (beta = .10, p =
.014) subscales of psychological empowerment predicted higher job satisfaction.
Organizational context variables that predicted job satisfaction included: social
capital (beta = .158, p = .012), organizational slack-time (beta = .096, p =
.029), and adequate orientation (beta = .088, p = .005). CONCLUSIONS: This study
suggests that individual allied healthcare provider and organizational context
features are both predictive of allied healthcare provider job satisfaction in
residential LTC settings. Unlike demographics and structural characteristics of
LTC facilities, all variables identified as important to allied healthcare
providers' job satisfaction in this study are potentially modifiable, and
therefore amenable to intervention.
PMID- 29940950
TI - Cross-border movement, economic development and malaria elimination in the
Kingdom of Saudi Arabia.
AB - Malaria at international borders presents particular challenges with regards to
elimination. International borders share common malaria ecologies, yet
neighboring countries are often at different stages of the control-to-elimination
pathway. Herein, we present a case study on malaria, and its control, at the
border between Saudi Arabia and Yemen. Malaria program activity reports, case
data, and ancillary information have been assembled from national health
information systems, archives, and other related sources. Information was
analyzed as a semi-quantitative time series, between 2000 and 2017, to provide a
plausibility framework to understand the possible contributions of factors
related to control activities, conflict, economic development, migration, and
climate. The malaria recession in the Yemeni border regions of Saudi Arabia is a
likely consequence of multiple, coincidental factors, including scaled
elimination activities, cross-border vector control, periods of low rainfall, and
economic development. The temporal alignment of many of these factors suggests
that economic development may have changed the receptivity to the extent that it
mitigated against surges in vulnerability posed by imported malaria from its
endemic neighbor Yemen. In many border areas of the world, malaria is likely to
be sustained through a complex congruence of factors, including poverty,
conflict, and migration.
PMID- 29940951
TI - Is Xpert MTB/RIF appropriate for diagnosing tuberculous pleurisy with pleural
fluid samples? A systematic review.
AB - BACKGROUND: Tuberculous pleurisy (TP) presents a diagnostic problem due to the
limitations of traditional diagnostic methods. Different studies with the Xpert
MTB/RIF assay have drawn variable conclusions about its values in TP diagnosis.
We conducted a meta-analysis to assess whether the Xpert MTB/RIF assay is
appropriate for the diagnosis of TP using pleural fluid samples. METHODS: A
systematic search of four literature databases in English and Chinese language
was performed to identify studies involving the use of Xpert MTB/RIF in patients
with TP confirmed by plural biopsy and/or mycobacterial culture. Pooled
sensitivity, specificity and accordance proportion were calculated, and the
forest plots were generated to assess the accuracy of Xpert MTB/RIF for TP
diagnosis. RESULTS: We identified 23 studies meeting our inclusion criteria. The
pooled sensitivity and specificity of Xpert MTB/RIF were 30% (95% CI: 21-42%, I2
= 87.93%) and 99% (95% CI: 97-100%, I2 = 96.20%), respectively, and the area
under the SROC curve (AUC) of Xpert MTB/RIF was 0.86 (95% CI: 0.83-0.89).
Compared with drug susceptibility testing (DST), the pooled accordance rate of
Xpert MTB/RIF in detecting rifampicin-susceptible cases and rifampicin-resistant
cases was 99% (95% CI: 95-104%, I2 = 8.7%) and 94% (95% CI: 86-102%),
respectively. CONCLUSIONS: Our analysis suggests that the Xpert MTB/RIF assay is
of limited value as a screening test for TP but has a high potential for
confirming TP diagnosis and differentiating TP from non-TB diseases using pleural
fluid samples.
PMID- 29940953
TI - Study protocol of a cluster randomized controlled trial to evaluate effectiveness
of a system for maintaining high-quality early essential newborn care in Lao PDR.
AB - BACKGROUND: Reduction in neonatal deaths has been a major challenge globally. To
prevent neonatal deaths, improvements in newborn care have been promoted
worldwide. The World Health Organization Western Pacific Regional Office has been
promoting the Early Essential Newborn Care (EENC), a package of specific simple
and cost-effective interventions, in their region. However, mere introduction of
EENC cannot reduce neonatal deaths unless quality of care is ensured. In Lao PDR,
the government introduced self-managed continuous monitoring as a sustainable way
to improve the quality of care described in the EENC. METHODS: A clustered
randomized controlled trial was designed to compare the effectiveness of self
managed continuous monitoring with external supervisory visits to monitor health
workers' satisfactory EENC performance and their knowledge and skills related to
the EENC in Lao PDR. Determinants of EENC performance will be measured with a
structured questionnaire developed based on the Theory of Planned Behaviour,
which predicts future behaviour. During self-managed continuous monitoring
activities, health workers in each district hospital will conduct periodical peer
reviews and feedback sessions. Fifteen district hospitals will be randomly
allocated into the self-managed continuous monitoring (intervention) and the
supervision (control) groups. Fifteen health workers routinely involved in
maternity and newborn care including physicians, midwives and other health staff
will be recruited from each hospital (effect size 0.6, intra-cluster correlation
coefficient 0.06, 5% alpha error and 80% power). We will compare the change in
the mean score of the determinants before and one year after randomisation
between the two groups. We will also compare the retention of knowledge and
skills related to the EENC between the two groups. The expected enrolment period
is July 20th, 2017 to July 20th, 2018. DISCUSSION: This is the first cluster
randomized trial to evaluate a self-managed continuous monitoring system for
quality maintenance of newborn care in a resource-limited country. This research
is conducted in collaboration with the Ministry of Health and international
organizations; therefore, if effective, this intervention would be applied in
larger areas of the country and the region. TRIAL REGISTRATION: This trial was
registered at UMIN-CTR on 15th of June, 2017. Registration number is
UMIN000027794 .
PMID- 29940952
TI - Circulating microRNAs and prediction of asthma exacerbation in childhood asthma.
AB - BACKGROUND: Circulating microRNAs have shown promise as non-invasive biomarkers
and predictors of disease activity. Prior asthma studies using clinical,
biochemical and genomic data have not shown excellent prediction of exacerbation.
We hypothesized that a panel of circulating microRNAs in a pediatric asthma
cohort combined with an exacerbation clinical score might predict exacerbation
better than the latter alone. METHODS: Serum samples from 153 children at
randomization in the Childhood Asthma Management Program were profiled for 754
microRNAs. Data dichotomized for asthma exacerbation one year after randomization
to inhaled corticosteroid treatment were used for binary logistic regression with
miRNA expressions and exacerbation clinical score. RESULTS: 12 of 125 well
detected circulating microRNAs had significant odd ratios for exacerbation with
miR-206 being most significant. Each doubling of expression of the 12 microRNA
corresponded to a 25-67% increase in exacerbation risk. Stepwise logistic
regression yielded a 3-microRNA model (miR-146b, miR-206 and miR-720) that,
combined with the exacerbation clinical score, had excellent predictive power
with a 0.81 AUROC. These 3 microRNAs were involved in NF-kbeta and GSK3/AKT
pathways. CONCLUSIONS: This combined circulating microRNA-clinical score model
predicted exacerbation in asthmatic subjects on inhaled corticosteroids better
than each constituent feature alone. TRIAL REGISTRATION: ClinicalTrials.gov
Identifier: NCT00000575 .
PMID- 29940954
TI - Allogeneic mesenchymal stem cells improve the wound healing process of sheep
skin.
AB - BACKGROUND: Skin wound healing includes a system of biological processes,
collectively restoring the integrity of the skin after injury. Healing by second
intention refers to repair of large and deep wounds where the tissue edges cannot
be approximated and substantial scarring is often observed. The objective of this
study was to evaluate the effects of mesenchymal stem cells (MSCs) in second
intention healing using a surgical wound model in sheep. MSCs are known to
contribute to the inflammatory, proliferative, and remodeling phases of the skin
regeneration process in rodent models, but data are lacking for large animal
models. This study used three different approaches (clinical, histopathological,
and molecular analysis) to assess the putative action of allogeneic MSCs at 15
and 42 days after lesion creation. RESULTS: At 15 days post-lesion, the wounds
treated with MSCs showed a higher degree of wound closure, a higher percentage of
re-epithelialization, proliferation, neovascularization and increased contraction
in comparison to a control group. At 42 days, the wounds treated with MSCs had
more mature and denser cutaneous adnexa compared to the control group. The MSCs
treated group showed an absence of inflammation and expression of CD3+ and CD20+.
Moreover, the mRNA expression of hair-keratine (hKER) was observed in the MSCs
treated group 15 days after wound creation and had increased significantly by 42
days post-wound creation. Collagen1 gene (Col1alpha1) expression was also greater
in the MSCs-treated group compared to the control group at both days 15 and 42.
CONCLUSION: Peripheral blood-derived MSCs may improve the quality of wound
healing both for superficial injuries and deep lesions. MSCs did not induce an
inflammatory response and accelerated the appearance of granulation tissue,
neovascularization, structural proteins, and skin adnexa.
PMID- 29940955
TI - Combining survey data, GIS and qualitative interviews in the analysis of health
service access for persons with disabilities.
AB - BACKGROUND: Equitable access to health services is a key ingredient in reaching
health for persons with disabilities and other vulnerable groups. So far,
research on access to health services in low- and middle-income countries has
largely relied on self-reported survey data. Realizing that there may be
substantial discrepancies between perceived and actual access, other methods are
needed for more precise knowledge to guide health policy and planning. The
objective of this article is to describe and discuss an innovative methodological
triangulation where statistical and spatial analysis of perceived distance and
objective measures of access is combined with qualitative evidence. METHODS: The
data for the study was drawn from a large household and individual questionnaire
based survey carried out in Namibia and Malawi. The survey data was combined with
spatial data of respondents and health facilities, key informant interviews and
focus group discussions. To analyse access and barriers to access, a model is
developed that takes into account both measured and perceived access. The geo
referenced survey data is used to establish four outcome categories of perceived
and measured access as either good or poor. Combined with analyses of the terrain
and the actual distance from where the respondents live to the health facility
they go to, the data allows for categorising areas and respondents according to
the four outcome categories. The four groups are subsequently analysed with
respect to variation in individual characteristics and vulnerability factors. The
qualitative component includes participatory map drawing and is used to gain
further insight into the mechanisms behind the different combinations of
perceived and actual access. RESULTS: Preliminary results show that there are
substantial discrepancies between perceived and actual access to health services
and the qualitative study provides insight into mechanisms behind such
divergences. CONCLUSION: The novel combination of survey data, geographical data
and qualitative data will generate a model on access to health services in poor
contexts that will feed into efforts to improve access for the most vulnerable
people in underserved areas.
PMID- 29940956
TI - Improving the performance of social health insurance system through increasing
outpatient expenditure reimbursement ratio: a quasi-experimental evaluation study
from rural China.
AB - BACKGROUND: China has set up a universal coverage social health insurance system
since the 2009 healthcare reform. Due to the inadequate funds, the social health
insurance system reimbursed the inpatient expenditures with much higher ratio
than outpatient expenditure. The gap in reimbursement ratios resulted in a rapid
rising hospitalization rate but poor health outcomes among the Chinese
population. A redistribution of social health insurance funds has become one of
the main challenges for the performance of Social Health Insurance. METHODS: Two
comparable counties, Dangyang County and Zhijiang County, in Hubei Province of
China, were sampled as the intervention group and the control group,
respectively. The Social Health Insurance Management Department of the
intervention group budgeted 600 yuan per capita per year to the patients with 3rd
stage hypertension to cover their outpatient expenditures. The outpatient
spending in the control group were paid out-of-pocket. The inpatient expenditures
reimbursement policies in both groups were not changed. Besides, the Social
Health Insurance Management Department of the intervention group budgeted 100
yuan per patient per year to township physicians and hospitals to provide health
management services for the patients. While, the health management services in
the control group were still provided by health workers. A Propensity Score
Matching model and Difference-in-differences model were used to estimate the net
effects of the intervention in dimensions of medical services utilization,
medical expenditures, SHI reimbursement, and health outcomes. RESULTS: One
thousand, six hundred and seventy three pairs of patients were taken as valid
subjects to conduct Difference-in-differences estimation after the Propensity
Score Matching. The net intervention effect is to increase outpatient frequency
by 3.3 (81.0%) times (P < 0.05), to decrease hospitalization frequency by 0.075 (
60.0%) times (P < 0.05), and to increase the per capita total medical service
utilization frequency by 3.225 (76.8%) times (P < 0.05). The per capita total
medical expenditure decreased 394.2 (- 27.7%) yuan. The SHI reimbursed 90.3 yuan
more per capita for the outpatient spending, but the per capita inpatient
expenditure reimbursement and per capita total medical expenditure reimbursement
decreased significantly by 282.6 (- 44.0%) yuan and 192.3 (- 28.5%) yuan,
respectively (P < 0.05). The intervention reduced the per capita inpatient out-of
pocket expenditure and the per capita total out-of-pocket expenditure by 192.8 (-
36.7%) yuan and 201.9 (- 29.9%) yuan, respectively (P < 0.05). The intervention
significantly decreased the diastolic blood pressure of the intervention group by
2.9 mmHg (P < 0.05) but had no significant impact on the systolic blood pressure
(- 7.9 mmHg, P > 0.05). CONCLUSION: For China and countries attempting to
establish a universal coverage SHI with inadequate funds, inpatient services were
expensive but might not produce good health outcomes. Outpatient care for
patients with chronic diseases should be fundamental, and outpatient expenditures
should be reimbursed with a higher ratio.
PMID- 29940958
TI - Caring for pregnant refugee women in a turbulent policy landscape: perspectives
of health care professionals in Calgary, Alberta.
AB - BACKGROUND: Female refugees can be a vulnerable population, often having suffered
through traumatic events that pose risks to their health, especially during
pregnancy. Pregnancy can be an entry point into the health care system, providing
health care professionals the opportunity to gain women's trust, connect refugees
with resources, and optimize the health of mother and child. Policies surrounding
the provision and funding of health care services to refugees can impact access
to and quality of care. The aim of our study was to understand the experiences of
health care professionals caring for pregnant refugee women in Calgary, AB,
taking into consideration recent contextual changes to the refugee landscape in
Canada. METHODS: We conducted ten semi-structured interviews with health care
professionals who provided regular care for pregnant refugee women at a refugee
health clinic and major hospital in Calgary, Alberta. Interviews were recorded,
transcribed, and analyzed using an interpretive description methodology. RESULTS:
Health care providers described several barriers when caring for pregnant
refugees, including language barriers, difficulty navigating the health care
system, and cultural barriers such as managing traditional gender dynamics, only
wanting a female provider and differences in medical practices. Providers managed
these barriers through strategies including using a team-based approach to care,
coordinating the patient's care with other services, and addressing both the
medical and social needs of the patient. The federal funding cuts added
additional challenges, as many refugees were left without adequate health
coverage and the system was complicated to understand. Health care providers
developed creative strategies to maximize coverage for their patients including
paying out of pocket or relying on donations to care for uninsured refugees.
Finally, the recent Syrian refugee influx has increased the demand on service
providers and further strained already limited resources. CONCLUSION: Health care
providers caring for pregnant refugee women faced complex cultural and system
level barriers, and used multiple strategies to address these barriers.
Additional system strains add extra pressure on health care professionals,
requiring them to quickly adjust and accommodate for new demands.
PMID- 29940957
TI - Describing the diurnal relationships between objectively measured mother and
infant physical activity.
AB - BACKGROUND: Evidence for the importance of accumulating sufficient physical
activity in the early years is mounting. This study aimed to determine the
relationship between maternal and infant objectively measured physical activity,
and to examine the diurnal interactions between these behaviours while accounting
for potential covariates. METHODS: Mothers and infants (n = 152 pairs; infants
aged 3-24 months) were recruited from Soweto, South Africa, and physical activity
was measured using a wrist worn accelerometer (Axivity AX3, Axivity Ltd.,
Newcastle-upon-Tyne, UK) for 3-7 days. Mothers completed sleep diaries recording
night time-in-bed (used as a proxy for nocturnal sleep status) for themselves and
their infant; and reported times during which their infant was in their personal
care (caregiver status) for each day during the measurement period. Significant
correlates of infant physical activity, as well as the interactions between
mother's physical activity, day of the week, sleep status, and caregiver status,
were included in panel regression analyses with infant physical activity as the
outcome. RESULTS: There was an equal distribution of boys and girls, and their
age ranged from 2.6 to 24.5 months. The majority of mothers (73%) did not spend
any time apart from their infant. During weekdays, the combined effect of
mother's physical activity (beta=0.11), the interactions between mother's
physical activity and caregiver status (beta=0.17), and sleep status (beta= -
0.04) on infant physical activity was beta=0.24; while during weekend days this
association was beta=0.21; and was largely moderated by the interaction between
the mother being with the infant and her activity levels (beta=0.23), but partly
attenuated by mother's physical activity independent of other variables (beta= -
0.04). For each hour of the day, for both mother and infant, peaks of physical
activity were higher when the mother was not the primary caregiver. CONCLUSIONS:
Infant physical activity levels were strongly associated with their mother's
activity levels particularly during the week; this relationship was stronger when
mothers were more active while looking after their infant. Mothers should be
encouraged to be active when looking after their children, particularly during
the week, and to provide infants with as much opportunity to be active as
possible.
PMID- 29940959
TI - Association of NOS1 gene polymorphisms with cerebral palsy in a Han Chinese
population: a case-control study.
AB - BACKGROUND: Cerebral palsy (CP) is the leading cause of motor disability in
children; however, its pathogenesis is unknown in most cases. Growing evidence
suggests that Nitric oxide synthase 1 (NOS1) is involved in neural development
and neurologic diseases. The purpose of this study was to determine whether
genetic variants of NOS1 contribute to CP susceptibility in a Han Chinese
population. METHODS: A case-control study involving 652 CP patients and 636
healthy controls was conducted. Six SNPs in the NOS1 gene (rs3782219, rs6490121,
rs2293054, rs10774909, rs3741475, and rs2682826) were selected, and the MassARRAY
typing technique was applied for genotyping. Data analysis was conducted using
SHEsis online software, and multiple test corrections were performed using SNPSpD
online software. RESULTS: There were no significant differences in genotype and
allele frequencies between patients and controls for the SNPs except rs6490121,
which deviated from Hardy-Weinberg equilibrium and was excluded from further
analyses. Subgroup analysis revealed differences in genotype frequencies between
the CP with neonatal encephalopathy group (CP + NE) and control group for
rs10774909, rs3741475, and rs2682826 (after SNPSpD correction, p = 0.004, 0.012,
and 0.002, respectively). The T allele of NOS1 SNP rs3782219 was negatively
associated with spastic quadriplegia (OR = 0.742, 95% CI = 0.600-0.918, after
SNPSpD correction, p = 0.023). There were no differences in allele or genotype
frequencies between CP subgroups and controls for the other genetic
polymorphisms. CONCLUSIONS: NOS1 is associated with CP + NE and spastic
quadriplegia, suggesting that NOS1 is likely involved in the pathogenesis of CP
and that it is a potential therapeutic target for treatment of cerebral injury.
PMID- 29940962
TI - Retraction Note to: Differences in the expression profiles of claudin proteins in
human nasopharyngeal carcinoma compared with non-neoplastic mucosa.
AB - The editor has retracted this article [1] because of flaws and inconsistencies in
the methodology, reporting and interpretation of the data.
PMID- 29940961
TI - Looking both ways: a review of methods for assessing research impacts on policy
and the policy utilisation of research.
AB - BACKGROUND: Measuring the policy and practice impacts of research is becoming
increasingly important. Policy impacts can be measured from two directions -
tracing forward from research and tracing backwards from a policy outcome. In
this review, we compare these approaches and document the characteristics of
studies assessing research impacts on policy and the policy utilisation of
research. METHODS: Keyword searches of electronic databases were conducted in
December 2016. Included studies were published between 1995 and 2016 in English
and reported methods and findings of studies measuring policy impacts of
specified health research, or research use in relation to a specified health
policy outcome, and reviews reporting methods of research impact assessment.
Using an iterative data extraction process, we developed a framework to define
the key elements of empirical studies (assessment reason, assessment direction,
assessment starting point, unit of analysis, assessment methods, assessment
endpoint and outcomes assessed) and then documented the characteristics of
included empirical studies according to this framework. RESULTS: We identified
144 empirical studies and 19 literature reviews. Empirical studies were derived
from two parallel streams of research of equal size, which we termed 'research
impact assessments' and 'research use assessments'. Both streams provided
insights about the influence of research on policy and utilised similar
assessment methods, but approached measurement from opposite directions. Research
impact assessments predominantly utilised forward tracing approaches while the
converse was true for research use assessments. Within each stream, assessments
focussed on narrow or broader research/policy units of analysis as the starting
point for assessment, each with associated strengths and limitations. The two
streams differed in terms of their relative focus on the contributions made by
specific research (research impact assessments) versus research more generally
(research use assessments) and the emphasis placed on research and the activities
of researchers in comparison to other factors and actors as influencers of
change. CONCLUSIONS: The Framework presented in this paper provides a mechanism
for comparing studies within this broad field of research enquiry. Forward and
backward tracing approaches, and their different ways of 'looking', tell a
different story of research-based policy change. Combining approaches may provide
the best way forward in terms of linking outcomes to specific research, as well
as providing a realistic picture of research influence.
PMID- 29940960
TI - Development of practice and consensus-based strategies including a treat-to
target approach for the management of moderate and severe juvenile
dermatomyositis in Germany and Austria.
AB - BACKGROUND: Juvenile dermatomyositis (JDM) is the most common inflammatory
myopathy in childhood and a major cause of morbidity among children with
pediatric rheumatic diseases. The management of JDM is very heterogeneous. The
JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define
consensus- and practice-based strategies in order to harmonize diagnosis,
treatment and monitoring of JDM. METHODS: The JDM working group was established
in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and
dermatologists with expertise in the management of JDM. Current practice patterns
of management in JDM had previously been identified via an online survey among
pediatric rheumatologists and neurologists. Using a consensus process consisting
of online surveys and a face-to-face consensus conference statements were defined
regarding the diagnosis, treatment and monitoring of JDM. During the conference
consensus was achieved via nominal group technique. Voting took place using an
electronic audience response system, and at least 80% consensus was required for
individual statements. RESULTS: Overall 10 individual statements were developed,
finally reaching a consensus of 92 to 100% regarding (1) establishing a
diagnosis, (2) case definitions for the application of the strategies (moderate
and severe JDM), (3) initial diagnostic testing, (4) monitoring and
documentation, (5) treatment targets within the context of a treat-to-target
strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target
strategy, (8) various glucocorticoid regimens, including intermittent intravenous
methylprednisolone pulse and high-dose oral glucocorticoid therapies with
tapering, (9) initial glucocorticoid-sparing therapy and (10) management of
refractory disease. CONCLUSION: Using a consensus process among JDM experts,
statements regarding the management of JDM were defined. These statements and the
strategies aid in the management of patients with moderate and severe JDM.
PMID- 29940963
TI - Comparison of pro- and anti-inflammatory responses in paired human primary airway
epithelial cells and alveolar macrophages.
AB - BACKGROUND: Airway epithelial cells and alveolar macrophages (AMs) are the first
line of defense in the lung during infection. Toll-like receptor (TLR) agonists
have been extensively used to define the regulation of inflammation in these
cells. However, previous studies were performed in non-paired airway epithelial
cells and AMs. The major goal of our study was to compare the pro- and anti
inflammatory responses of paired human primary airway epithelial cells and AMs to
TLR3 and TLR4 agonists. METHODS: Tracheobronchial epithelial cells (TBEC) and AMs
from four smokers and four non-smokers without lung disease were cultured with or
without Poly(I:C) (PIC) (a TLR3 agonist) or LPS (a TLR4 agonist) for 4, 24 and 48
h. The immune responses of paired cells were compared. RESULTS: TBEC and AMs
showed stronger pro-inflammatory cytokine (e.g., IL-8) responses to PIC and LPS,
respectively. TLR3 and TLR4 mRNA levels were similar in non-stimulated TBEC and
AMs. However, PIC stimulation in AMs led to sustained up-regulation of the immune
negative regulators Tollip and A20, which may render AMs less sensitive to PIC
stimulation than TBEC. Unlike AMs, TBEC did not increase NF-kappaB activation
after LPS stimulation. Interestingly, smoking status was correlated with less
TLR3 and IRAK-M expression in non-stimulated TBEC, but not in AMs. PIC-stimulated
TBEC and LPS-stimulated AMs from smokers vs. non-smokers produced more IL-8.
Finally, we show that expression of A20 and IRAK-M is strongly correlated in the
two paired cell types. CONCLUSIONS: By using paired airway epithelial cells and
AMs, this study reveals how these two critical types of lung cells respond to
viral and bacterial pathogen associated molecular patterns, and provides
rationale for modulating immune negative regulators to prevent excessive lung
inflammation during respiratory infection.
PMID- 29940964
TI - Development and application of a monoclonal antibody-based blocking ELISA for
detection of antibodies to Tembusu virus in multiple poultry species.
AB - BACKGROUND: Tembusu virus (TMUV) is a member of the genus Flavivirus. Outbreak of
this virus infection in duck flocks was first observed in China in April 2010,
causing severe egg drop and neurological signs in laying ducks. Recently reported
duck infections in southeastern Asia highlighted the need for well-validated
diagnostic methods of TMUV surveillance to understand its epidemiological
characteristics and maintenance in nature. Several enzyme-linked immunosorbent
assays (ELISAs) for the detection of TMUV infection have been reported, but none
have been applied to high-throughput diagnostics. RESULTS: In this study, a
monoclonal antibody (MAb) against TMUV was generated and characterized. MAb 9E4
was shown to bind specifically to a disulfide bond-dependent epitope on the
domain I/II of TMUV E protein, and a blocking ELISA was established based on this
MAb. The cut-off percentage inhibition value for negative sera was set at 30%. By
comparison with the virus neutralization test, the specificity and sensitivity of
the blocking ELISA were 96.37% and 100%, respectively, and the kappa value was
0.966, based on 416 serum samples collected from both experimentally and
clinically infected ducks, geese and chickens. A good correlation (r2 = 07998, P
< 0.001) was observed between the blocking ELISA and plaque reduction
neutralization test (PRNT) titers. Using archived duck serum samples collected
between 2009 and 2015, the seroprevalence in duck flocks raised in Northern China
was estimated by blocking ELISA. CONCLUSIONS: Our MAb-based blocking ELISA
provides a reliable and rapid diagnostic tool for serological monitoring of TMUV
infection and evaluation of immune status following TMUV vaccination in multiple
poultry species.
PMID- 29940965
TI - Quantitative proteomics analysis of vitreous body from type 2 diabetic patients
with proliferative diabetic retinopathy.
AB - BACKGROUND: To compare the abundance of vitreous proteins between the patients
with proliferative diabetic retinopathy (PDR) and idiopathic macular hole (IMH).
METHODS: In this study, we performed mass spectrometry-based label-free
quantitative proteomics analysis of vitreous samples from type 2 diabetic
patients with PDR (n = 9) and IMH subjects (n = 9) and identified the abundance
of 610 proteins. RESULTS: Out of 610 proteins, 64 proteins (Group A) were unique
to PDR patients, while 212 proteins (Group B) could be identified in IMH vitreous
only. Among the other 334 proteins that could be detected in both PDR and IMH
eyes, 62 proteins differed significantly (p < 0.05, fold change > 2), which
included 52 proteins (Group C) and 10 proteins (Group D) over- and under
expressed in PDR vitreous compared with the control. All proteins in these four
groups were counted as significant proteins in our study. CONCLUSIONS: We
identified and quantified 610 proteins in total, which included 338 significant
proteins in our study. Protein distribution analysis demonstrated a clear
separation of protein expression in PDR and IMH. The protein function analysis
illustrated that immunity and transport related proteins might be associated with
PDR.
PMID- 29940966
TI - Improvement of n-caproic acid production with Ruminococcaceae bacterium CPB6:
selection of electron acceptors and carbon sources and optimization of the
culture medium.
AB - BACKGROUND: Global energy and resource shortages make it necessary to quest for
renewable resources. n-Caproic acid (CA) production based on carboxylate platform
by anaerobic fermentation is booming. Recently, a novel Ruminococcaceae bacterium
CPB6 is shown to be a potential biotransformation factory for CA production from
lactate-containing wastewater. However, little is known about the effects of
different electron acceptors (EAs) on the fermentative products of strain CPB6,
as well as the optimum medium for CA production. RESULTS: In this study, batch
experiments were performed to investigate the fermentative products of strain
CPB6 in a lactate medium supplemented with different EAs and sugars.
Supplementation of acetate, butyrate and sucrose dramatically increased cell
growth and CA production. The addition of propionate or pentanoate resulted in
the production of C5 or C7 carboxylic acid, respectively. Further, a Box-Behnken
experiment was conducted to optimize the culture medium for CA production. The
result indicated that a medium containing 13.30 g/L sucrose, 22.35 g/L lactate
and 16.48 g/L butyrate supported high-titer CA production (16.73 g/L) with a
maximum productivity of 6.50 g/L/day. CONCLUSIONS: This study demonstrated that
strain CPB6 could produce C6-C7 carboxylic acids from lactate (as electron donor)
with C2-C5 short-chain carboxylic acids (as EAs), but CA (C6 carboxylic acid) was
the most major and potential product. Butyrate and sucrose were the most
significant EA and carbon source respectively for CA production from lactate by
strain CPB6. High titer of CA can be produced from a synthetic substrate
containing sucrose, lactate and butyrate. The work provided significant
implications for improving CA production in industry-scale.
PMID- 29940967
TI - Ciliated conical epithelial cell protrusions point towards a diagnosis of primary
ciliary dyskinesia.
AB - BACKGROUND: Primary ciliary dyskinesia can result from a number of different
ciliary defects that adversely affect ciliary function resulting markedly reduced
or absent mucociliary clearance. Improvement in diagnostic testing is an area of
current research. During diagnostic evaluation of PCD we observed ciliated
conical protrusions from part of the apical surface of ciliated cells in those
diagnosed with PCD. The aim of this study was to investigate if this abnormality
was specific to PCD. METHODS: Epithelial edges from 67 consecutively diagnosed
PCD patients, 67 patients consecutively referred for PCD diagnostic testing in
whom PCD was excluded, 22 with asthma and 18 with Cystic Fibrosis (CF) were
studied retrospectively in a blinded manner using light microscopy. RESULTS:
Forty six out of 67 patients with PCD had ciliated conical epithelial
protrusions, whereas none were seen in patients where PCD was excluded, or in
patients with asthma or CF. The sensitivity, specificity, positive predictive
value and negative predictive value for the presence of the ciliated conical
protrusions to predict a diagnosis of PCD were 76.5, 100, 100 and 77%
respectively. CONCLUSIONS: Characteristic ciliated conical protrusions from
ciliated epithelial cells maybe a useful pointer to the diagnosis of PCD.
However, their absence does not exclude the diagnosis of PCD.
PMID- 29940968
TI - Reduction of malaria prevalence after introduction of artemisinin-combination
therapy in Mbeya Region, Tanzania: results from a cohort study with 6773
participants.
AB - BACKGROUND: A marked decline in malaria morbidity and mortality has been reported
after the introduction of artemisinin-based combination therapy (ACT) in high
malaria prevalence countries in Africa. Data on the impact of ACT and on the
prevalence of malaria has so far been scarce for Southwest Tanzania. METHODS:
Between 2005 and 2011, a large general population cohort in the Mbeya Region in
the south-west of Tanzania has been surveyed within the EMINI-study (Evaluation
and Monitoring of the Impact of New Interventions). Participants were examined
once per year, including rapid diagnostic testing for malaria. ACT was introduced
in the region according to national guidelines in the time period 2006/2007,
replacing sulfadoxine/pyrimethamine as first-line therapy. In four study sites,
6773 individuals who participated in the first two of three consecutive survey
visits in the period from 2006 to 2009 were included in this analysis. The
prevalence of Plasmodium infection prior to and after the introduction of ACT was
compared by logistic regression, with consideration of climatic variability, age,
sex, socio-economic status and bed net use as potential confounders. RESULTS: A
significant reduction over time in the prevalence of Plasmodium falciparum
infection from 2.5 to 0.3% was shown across the four study sites. The decline was
not explained by other factors included in the analysis, therefore, the decline
over time most likely reflects the impact of introduction of ACT in the study
area. CONCLUSIONS: The longitudinal study showed a significant and relevant
decline in the prevalence of P. falciparum infection after introduction of ACT,
which could not be explained by potential confounders. The data suggests that
artemisinin-based combinations are not only an effective instrument for reduction
of immediate morbidity and mortality, but also for reduction of transmission
rates.
PMID- 29940969
TI - Metabolic fate of pregnene-based steroids in the lactonization pathway of
multifunctional strain Penicillium lanosocoeruleum.
AB - BACKGROUND: Metabolic activities of microorganisms to modify the chemical
structures of organic compounds became an effective tool for the production of
high-valued steroidal drugs or their precursors. Currently research efforts in
production of steroids of pharmaceutical interest are focused on either
optimization of existing processes or identification of novel potentially useful
bioconversions. Previous studies demonstrated that P. lanosocoeruleum KCH 3012
metabolizes androstanes to the corresponding lactones with high yield. In order
to explore more thoroughly the factors determining steroid metabolism by this
organism, the current study was initiated to delineate the specificity of this
fungus with respect to the cleavage of steroid side chain of progesterone and
pregnenolone The effect of substituents at C-16 in 16-dehydropregnenolone,
16alpha,17alpha-epoxy-pregnenolone and 16alpha-methoxy-pregnenolone on the
pattern of metabolic processing of these steroids was also investigated. RESULTS
AND DISCUSSION: All of the analogues tested (except the last of the listed) in
multi-step transformations underwent the Baeyer-Villiger oxidation to their delta
D-lactones. The activity of 3beta-HSD was a factor affecting the composition of
the product mixtures. 16alpha,17alpha-epoxy-pregnenolone underwent a rare epoxide
opening with retention stereochemistry to give four 16alpha-hydroxy-lactones.
Apart from oxidative transformations, a reductive pathway was revealed with the
unique hydrogenation of 5-ene double bond leading to the formation of
3beta,16alpha-dihydroxy-17a-oxa-D-homo-5alpha-androstan-17-one. 16alpha-Methoxy
pregnenolone was transformed to the 20(R)-alcohol with no further conversion.
CONCLUSIONS: This work clearly demonstrated that P. lanosocoeruleum KCH 3012 has
great multi-functional catalytic properties towards the pregnane-type steroids.
Studies have highlighted that a slight modification of the D-ring of substrates
may control metabolic fate either into the lactonization or reductive and
oxidative pathways. Possibility of epoxide opening by enzymes from this
microorganism affords a unique opportunity for generation of novel bioactive
steroids.
PMID- 29940970
TI - Making free public healthcare attractive: optimizing health equity funds in
Cambodia.
AB - BACKGROUND: Following the introduction of user fees in Cambodia, Health Equity
Funds (HEF) were developed to enable poor people access to public health services
by paying public health providers on their behalf, including non-medical costs
for hospitalised beneficiaries (HEFB). The national scheme covers 3.1 million pre
identified HEFB. Uptake of benefits, however, has been mixed and a substantial
proportion of poor people still initiate care at private facilities where they
incur considerable out-of-pocket costs. We examine the benefits of additional
interventions compared to existing stand-alone HEF scenarios in stimulating care
seeking at public health facilities among eligible poor people. METHODS: We
report on three configurations of HEF and their ability to attract HEFB to
initiate care at public health facilities and their degree of financial risk
protection: HEF covering only hospital services (HoHEF), HEF covering health
centre and hospital services (CHEF), and Integrated Social Health Protection
Scheme (iSHPS) that allowed non-HEFB community members to enrol in HEF. The iSHPS
also used vouchers for selected health services, pay-for-performance for quantity
and quality of care, and interventions aimed at increasing health providers'
degree of accountability. A cross sectional survey collected information from
1636 matched HEFB households in two health districts with iSHPS and two other
health districts without iSHPS. Respondents were stratified according to the
three HEF configurations for the descriptive analysis. RESULTS: The findings
indicated that the proportion of HEFB who sought care first from public health
providers in iSHPS areas was 55.7%, significantly higher than the 39.5% in the
areas having HEF with health centres (CHEF) and 13.4% in the areas having HEF
with hospital services only (HoHEF). The overall costs (out-of-pocket and
transport) associated with the illness episode were lowest for cases residing
within iSHPS sites, US$10.4, and highest in areas where health centres were not
included in the package (HoHEF), US$20.7. Such costs were US$19.5 at HEF with
health centres (CHEF). CONCLUSIONS: The findings suggest that HEF encompassing
health centre and hospital services and complemented by additional interventions
are better than stand-alone HEF in attracting sick HEFB to public health
facilities and lowering out-of-pocket expenses associated with healthcare
seeking.
PMID- 29940971
TI - Are aortic coarctation and rheumatoid arthritis different models of aortic
stiffness? Data from an echocardiographic study.
AB - BACKGROUND: Patients who underwent a successful repair of the aortic coarctation
(CoA) show high risk for cardiovascular (CV) events. Mechanical and structural
abnormalities in the ascending aorta (Ao) might have a role in the prognosis of
CoA patients. We analyzed the elastic properties of Ao measured as aortic
stiffness index (AoSI) in CoA patients in the long-term period and we compared
AoSI with a cohort of 38 patients with rheumatoid arthritis (RA) and 38 non-RA
matched controls. METHODS: Data from 19 CoA patients were analyzed 28 +/- 13
years after surgery. Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th
percentile of the AoSI detected in our reference healthy population). AoSI was
assessed at the level of the aortic root by two-dimensional guided M-mode
evaluation. RESULTS: CoA patients showed more than two-fold higher AoSI compared
to RA and controls (9.8 +/- 12.6 vs 4.8 +/- 2.5% and 3.1 +/- 2.0%, respectively;
all p < 0.05 and in 5 of 19 patients with CoA (26%) AoSI was exceptionally high.
The 5 patients with abnormally high AoSI were older with higher BP, LV mass and
prevalence of LV diastolic dysfunction. Multiple linear regression analysis
revealed that AoSI was independently related to the presence of LV hypertrophy
and higher LV relative wall thickness. CONCLUSIONS: CoA patients have higher AoSI
levels than RA patients and non-RA matched controls. AoSI levels are abnormally
high in a small sub-group of CoA patients who show a very high-risk clinical
profile for adverse CV events.
PMID- 29940972
TI - Triglyceride profiling in adipose tissues from obese insulin sensitive, insulin
resistant and type 2 diabetes mellitus individuals.
AB - BACKGROUND: Lipid intermediates produced during triacylglycerols (TAGs) synthesis
and lipolysis in adipocytes interfere with the intracellular insulin signaling
pathway and development of insulin resistance. This study aims to compare TAG
species and their fatty acid composition in adipose tissues from insulin
sensitive (IS), insulin resistant (IR) and type 2 diabetes mellitus (T2DM) obese
individuals. METHODS: Human subcutaneous and omental adipose tissue biopsies were
obtained from 64 clinically characterized obese individuals during weight
reduction surgery. TAGs were extracted from the adipose tissues using the Bligh
and Dyer method, then were subjected to non-aqueous reverse phase ultra-high
performance liquid chromatography and full scan mass spectrometry acquisition and
data dependent MS/MS on LTQ dual cell linear ion trap. TAGs and their fatty acid
contents were identified and compared between IS, IR and T2DM individuals and
their levels were correlated with metabolic traits of participants and the
adipogenic potential of preadipocyte cultures established from their adipose
tissues. RESULTS: Data revealed 76 unique TAG species in adipose tissues
identified based on their exact mass. Analysis of TAG levels revealed a number of
TAGs that were significantly altered with disease progression including C46:4,
C48:5, C48:4, C38:1, C50:3, C40:2, C56:3, C56:4, C56:7 and C58:7. Enrichment
analysis revealed C12:0 fatty acid to be associated with TAGs least abundant in
T2DM whereas C18:3 was found in both depleted and enriched TAGs in T2DM.
Significant correlations of various adipose tissue-derived TAG species and
metabolic traits were observed, including age and body mass index, systemic total
cholesterol, TAGs, and interleukin-6 in addition to adipogenic potential of
preadipocytes derived from the same adipose tissues. CONCLUSION: Pilot data
suggest that adipose tissues from obese IR and T2DM individuals exhibit TAG
specific signatures that may contribute to their increased risk compared to their
IS counterparts. Future experiments are warranted to investigate the functional
relevance of these specific lipidomic profiles.
PMID- 29940973
TI - Practices and knowledge of female gynecologists regarding contraceptive use: a
real-world Chinese survey.
AB - BACKGROUND: There is no evidence of the practices of obstetricians and
gynecologists (OB/GYNs) regarding contraceptive use and determinants influencing
contraceptive choices, including emergency methods such as combined oral
contraceptives (COCs) and levonorgestrel intrauterine system (LNGIUS). This
survey determines the practices and knowledge among Chinese female OB/GYNs
regarding modern contraceptive methods. METHODS: A multicenter questionnaire was
completed by 2000 female OB/GYNs participating in training courses organized by
the gynecological endocrinology training committee of the Chinese Medical Doctor
Association from February to May 2013. RESULTS: This survey achieved a response
rate of 51.4%. The rate of induced abortion among this group was 56.3%; this may
be attributable to unreliable contraceptive methods (55.5%) and failure of
reliable contraceptive methods (18.9%). Intrauterine devices (IUDs) were more
commonly used by parous women than nulliparous women (42.6% vs 1.7%; p < 0.0001),
followed by condom and rhythm method (24.2% vs 20.8%). However, nulliparous women
commonly used rhythm method (48.3% vs 3.3%; p < 0.0001) and condoms (19.2% vs
10.5%; p = 0.008). OB/GYNs demonstrated misconceptions of OB/GYNs about COCs,
such as the risk of breast cancer, amenorrhea and premature ovarian failure, and
decreased fertility as reported by 37.10, 10.6, and 7.5% of the respondents,
respectively. CONCLUSIONS: IUDs were commonly used by parous Chinese OB/GYNs.
Unreliable contraceptive methods and misconceptions about the side effects of
COCs may result in the high rate of unintended pregnancies. Hence, awareness of
safe and effective contraceptive methods should be strengthened among OB/GYNs in
China.
PMID- 29940974
TI - Comparison between Wavefront-optimized and corneal Wavefront-guided
Transepithelial photorefractive keratectomy in moderate to high astigmatism.
AB - BACKGROUND: To compare the clinical outcomes of wavefront-optimized (WFO)
transepithelial photorefractive keratectomy (trans-PRK) and corneal wavefront
guided (CWFG) trans-PRK for myopic eyes with moderate to high astigmatism.
METHODS: One hundred ninety-six eyes (196 patients) with moderate to high
astigmatism (>= 1.75 D) treated with WFO or CWFG trans-PRK (101 and 95 eyes,
respectively) were retrospectively registered. Safety, efficacy, predictability,
vector analysis, and corneal aberrations were compared between groups
preoperatively and at 6 months postoperatively. RESULTS: At postoperative 6
months, the mean logMAR uncorrected distance visual acuity was similar in the WFO
(- 0.07 +/- 0.08) and CWFG (- 0.07 +/- 0.07) groups. Safety, efficacy, and
predictability of refractive and visual outcomes were also similar. The
correction indices were 1.02 +/- 0.14 and 1.03 +/- 0.13 in the WFO and CWFG
groups, respectively, with no significant difference. The absolute values of the
angle of error were significantly higher in the WFO group (2.28 +/- 2.44 vs. 1.40
+/- 1.40; P = 0.002). Corneal total root mean square higher-order aberrations and
corneal spherical aberrations increased postoperatively in both groups; however,
the change was smaller in the CWFG group. Corneal coma showed a significant
increase postoperatively only in the WFO group. CONCLUSIONS: WFO and CWFG trans
PRK are safe and effective for correcting moderate to high astigmatism. However,
CWFG trans-PRK provides a more predictable astigmatism correction axis and fewer
induced corneal aberrations.
PMID- 29940975
TI - Cancer prevalence among flight attendants compared to the general population.
AB - BACKGROUND: Flight attendants are an understudied occupational group, despite
undergoing a wide range of adverse job-related exposures, including to known
carcinogens. In our study, we aimed to characterize the prevalence of cancer
diagnoses among U.S. cabin crew relative to the general population. METHODS: In
2014-2015, we surveyed participants of the Harvard Flight Attendant Health Study.
We compared the prevalence of their self-reported cancer diagnoses to a
contemporaneous cohort in the National Health and Nutrition Examination Survey
(NHANES 2013-2014) using age-weighted standardized prevalence ratios (SPRs). We
also analyzed associations between job tenure and the prevalence of selected
cancers, using logistic regression and adjusting for potential confounders.
RESULTS: Compared to NHANES participants with a similar socioeconomic status (n =
2729), flight attendants (n = 5366) had a higher prevalence of every cancer we
examined, especially breast cancer, melanoma, and non-melanoma skin cancer among
females. SPR for these conditions were 1.51 (95% CI: 1.02, 2.24), 2.27 (95% CI:
1.27, 4.06), and 4.09 (95% CI: 2.70, 6.20), respectively. Job tenure was
positively related to non-melanoma skin cancer among females, with borderline
associations for melanoma and non-melanoma skin cancers among males. Consistent
with previous studies, we observed associations between job tenure and breast
cancer among women who had three or more children. CONCLUSIONS: We observed
higher rates of specific cancers in flight attendants compared the general
population, some of which were related to job tenure. Our results should be
interpreted in light of self-reported health information and a cross-sectional
study design. Future longitudinal studies should evaluate associations between
specific exposures and cancers among cabin crew.
PMID- 29940976
TI - Pathological changes and bacteriological assessments in the urinary tract of
pregnant goats experimentally infected with Brucella melitensis.
AB - BACKGROUND: This study was conducted to investigate the pathological changes and
distribution of B. melitensis in the urinary tract of pregnant goats following
acute experimental infection. Six Jamnapari crossbred does in their third
trimester of pregnancy were randomly assigned into two groups; Group 1 was
uninfected control and Group 2 was inoculated conjunctival with 0.1 mL of the
inoculums containing 109 cfu/mL of live B. melitensis. All does were sacrificed
30 days post-inoculation before the kidney, ureter, urinary bladder, urethra and
vaginal swab were collected for isolation of B. melitensis. The same tissue
samples were fixed in 10% neutral buffered formalin for hematoxylin and eosin,
and immunoperoxidase staining. RESULTS: None of the goats showed clinical signs
or gross lesions. The most consistent histopathology finding was the infiltration
of mononuclear cells, chiefly the macrophages with few lymphocytes and
occasionally neutrophils in all organs along the urinary tract of the infected
goats of Group 2. Other histopathology findings included mild necrosis of the
epithelial cells of the renal tubules, congestion and occasional haemorrhages in
the various tissues. Kidneys showed the most severe lesions. Immunoperoxidase
staining revealed the presence of B. melitensis within the infiltrating
macrophages and the epithelium of renal tubules, ureter, urethra and urinary
bladder. Most extensive distribution was observed in the urinary bladder.
Brucella melitensis was successfully isolated at low concentration (3.4 * 103
cfu/g) in the various organs of the urinary tract and at high concentration (2.4
* 108 cfu/mL) in the vaginal swabs of all infected goats. Although B. melitensis
was successfully isolated from the various organs of the urinary tract, it was
not isolated from the urine samples that were collected from the urinary bladder
at necropsy. CONCLUSION: This study demonstrates the presence of low
concentrations of B. melitensis in the organs of urinary tract of pregnant does,
resulting in mild histopathology lesions. However, B. melitensis was not isolated
from the urine that was collected from the urinary bladder.
PMID- 29940977
TI - The 2017 Dutch Physical Activity Guidelines.
AB - BACKGROUND: The objective of this study was to derive evidence-based physical
activity guidelines for the general Dutch population. METHODS: Two systematic
reviews were conducted of English language meta-analyses in PubMed summarizing
separately randomized controlled trials and prospective cohort studies on the
relation between physical activity and sedentary behaviour on the one hand and
the risk of all-cause mortality and incidence of 15 major chronic diseases and
conditions on the other hand. Other outcome measures were risk factors for
cardiovascular disease and type 2 diabetes, physical functioning, and fitness. On
the basis of these reviews, an expert committee derived physical activity
guidelines. In deriving the guidelines, the committee first selected only
experimental and observational prospective findings with a strong level of
evidence and then integrated both lines of evidence. RESULTS: The evidence found
for beneficial effects on a large number of the outcome measures was sufficiently
strong to draw up guidelines to increase physical activity and reduce sedentary
behaviour, respectively. At the same time, the current evidence did not provide a
sufficient basis for quantifying how much physical activity is minimally needed
to achieve beneficial health effects, or at what amount sedentary behaviour
becomes detrimental. A general tenet was that at every level of current activity,
further increases in physical activity provide additional health benefits, with
relatively larger effects among those who are currently not active or active only
at light intensity. Three specific guidelines on (1) moderate- and vigorous
intensity physical activity, (2) bone- and muscle-strengthening activities, and
(3) sedentary behaviour were formulated separately for adults and children.
CONCLUSIONS: There is an unabated need for evidence-based physical activity
guidelines that can guide public health policies. Research in which physical
activity is measured both objectively (quantity) and subjectively (type and
quality) is needed to provide better estimates of the type and actual amount of
physical activity required for health.
PMID- 29940978
TI - Associations between circulating full-length angiopoietin-like protein 8 levels
and severity of coronary artery disease in Chinese non-diabetic patients: a case
control study.
AB - BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8), which is a novel hormone
produced in liver and adipose tissue, is involved in regulating lipid metabolism.
Patients with diabetes and coronary artery disease (CAD) have remarkably higher
levels of ANGPTL8 than those with only diabetes. However, no studies have
investigated the involvement of ANGPTL8 in CAD in Chinese non-diabetic
individuals. Therefore, we investigated full-length circulating ANGPTL8 levels in
patients with CAD and the association between ANGPT8 levels and severity of CAD
in Chinese individuals without diabetes. METHODS: We performed a case-control
study in 149 Chinese non-diabetic subjects, including 80 patients with CAD and 69
controls. The Gensini stenosis scoring system was used to assess the severity of
CAD. Circulating full-length ANGPTL8 levels were measured by an enzyme-linked
immunosorbent assay kit. The associations between circulating full-length ANGPTL8
levels and CAD were determined by multivariate logistic regression analysis. The
association between ANGPTL8 levels and Gensini scores was determined by
multivariate linear regression analysis. RESULTS: Circulating full-length ANGPTL8
levels were significantly higher in Chinese non-diabetic patients with CAD
compared with controls (665.90 +/- 243.49 vs 462.27 +/- 151.85 pg/ml, P < 0.001).
After adjusting for confounding factors, we found that circulating full-length
ANGPTL8 levels were an independent risk factor for CAD (odds ratio = 2.002/100 pg
ANGPTL8, 95% CI 1.430-2.803, P < 0.001) and circulating ANGPTL8 levels were
positively associated with the Gensini score (beta = 5.701/100 pg ANGPTL8, 95% CI
1.306-10.096, P = 0.012). CONCLUSIONS: This study shows that the circulating
ANGPTL8 levels are significantly increased in patients with CAD compared with
controls in Chinese non-diabetic individuals. Circulating full-length ANGPTL8
levels are an independent risk factor for CAD and they are positively associated
with the severity of CAD. Trial registration This study was registered in the
Chinese Clinical Trial Registry (No. ChiCTR-COC-17010792).
PMID- 29940979
TI - Cardiac, bone and growth plate manifestations in hypocalcemic infants: revealing
the hidden body of the vitamin D deficiency iceberg.
AB - BACKGROUND: Whilst hypocalcemic complications from vitamin D deficiency are
considered rare in high-income countries, they are highly prevalent among Black,
Asian and Minority Ethnic (BAME) group with darker skin. To date, the extent of
osteomalacia in such infants and their family members is unknown. Our aim was to
investigate clinical, cardiac and bone histomorphometric characteristics, bone
matrix mineralization in affected infants and to test family members for
biochemical evidence of osteomalacia. CASE PRESENTATION: Three infants of BAME
origin (aged 5-6 months) presented acutely in early-spring with cardiac arrest,
respiratory arrest following seizure or severe respiratory distress, with
profound hypocalcemia (serum calcium 1.22-1.96 mmol/L). All infants had dark skin
and vitamin D supplementation had not been addressed during child surveillance
visits. All three had severely dilated left ventricles (z-scores + 4.6 to + 6.5)
with reduced ejection fraction (25-30%; normal 55-70), fractional shortening (7
to 15%; normal 29-40) and global hypokinesia, confirming hypocalcemic dilated
cardiomyopathy. They all had low serum levels of 25 hydroxyvitamin D (25OHD < 15
nmol/L), and elevated parathyroid hormone (PTH; 219-482 ng/L) and alkaline
phosphatase (ALP; 802-1123 IU/L), with undiagnosed rickets on radiographs. One
infant died from cardiac arrest. At post-mortem examination, his growth plate
showed a widened, irregular zone of hypertrophic chondrocytes. Histomorphometry
and backscattered electron microscopy of a trans-iliac bone biopsy sample
revealed increased osteoid thickness (+ 262% of normal) and osteoid volume/bone
volume (+ 1573%), and extremely low bone mineralization density. Five of the nine
tested family members had vitamin D deficiency (25OHD < 30 nmol/L), three had
insufficiency (< 50 nmol/L) and 6/9 members had elevated PTH and ALP levels.
CONCLUSIONS: The severe, hidden, cardiac and bone pathology described here
exposes a failure of public health prevention programs, as complications from
vitamin D deficiency are entirely preventable by routine supplementation. The
family investigations demonstrate widespread deficiency and undiagnosed
osteomalacia in ethnic risk groups and call for protective legislation.
PMID- 29940980
TI - Assessing health status over time: impact of recall period and anchor question on
the minimal clinically important difference of copd health status tools.
AB - BACKGROUND: The Minimal Clinically Important Difference (MCID) assesses what
change on a measurement tool can be considered minimal clinically relevant.
Although the recall period can influence questionnaire scores, it is unclear if
it influences the MCID. This study is the first to examine longitudinally the
impact of the recall period of an anchor question and its design on the MCID of
COPD health status tools using the COPD Assessment Test (CAT), Clinical COPD
Questionnaire (CCQ) and the St. George's Respiratory Questionnaire (SGRQ).
METHODS: Moderate to very severe COPD patients without respiratory co-morbidities
were recruited during 3-week Pulmonary Rehabilitation (PR). CAT, CCQ and SGRQ
were completed at baseline, discharge, 3, 6, 9 and 12 months. A 15-point Global
Rating of Change scale (GRC) was completed at each follow-up. A five-point GRC
was used as second anchor at 12 months. Mean change scores of a subset of
patients indicating a minimal improvement on each of the anchor questions were
considered the MCID. The MCID estimates over different time periods were compared
with one another by evaluating the degree of overlap of Confidence Intervals (CI)
adjusted for dependency. RESULTS: In total 451 patients were included (57.9 +/-
6.6 years, 65% male, 50/39/11% GOLD II/III/IV), of which 309 completed follow-up.
Baseline health status scores were 20.2 +/- 7.3 (CAT), 2.9 +/- 1.2 (CCQ) and 50.7
+/- 17.3 (SGRQ). MCID estimates for improvement ranged - 3.1 to - 1.4 for CAT, -
0.6 to - 0.3 for CCQ, and - 10.3 to - 7.6 for SGRQ. Absolute higher - though not
significant - MCIDs were observed for CAT and CCQ directly after PR.
Significantly absolute lower MCID estimates were observed for CAT (difference -
1.4: CI -2.3 to - 0.5) and CCQ (difference - 0.2: CI -0.3 to -0.1) using a five
point GRC. CONCLUSIONS: The recall period of a 15-point anchor question seemed to
have limited impact on the MCID for improvement of CAT, CCQ and SGRQ during PR;
although a 3-week MCID estimate directly after PR might lead to absolute higher
values. However, the design of the anchor question was likely to influence the
MCID of CAT and CCQ. TRIAL REGISTRATION: RIMTCORE trial # DRKS00004609 and #12107
(Ethik-Kommission der Bayerischen Landesarztekammer).
PMID- 29940981
TI - Interleukin-32: its role in asthma and potential as a therapeutic agent.
AB - Interleukin (IL)-32, also named natural killer cell transcript 4 (NK4), has
increasingly been described as an immunoregulator that controls cell
differentiation and cell death and is involved in the stimulation of anti-/pro
inflammatory cytokines. Abnormal presence of IL-32 has been repeatedly noticed
during the pathogenesis of allergic, infectious, cancerous, and inflammatory
diseases. Of particular note was the observation of the anti-inflammatory
property of IL-32 in a murine ovalbumin model of allergic asthma. Compared to
wild-type mice, IL-32gamma transgenic mice show decreased levels of inflammatory
cells, recruited eosinophils, and lymphocytes in bronchoalveolar lavage fluid in
a mouse model of acute asthma. To date, the molecular mechanism underlying the
role of IL-32 in asthma remains to be elucidated. This review aims to summarize
recent advances in the pathophysiology of asthma and describe the links to IL-32.
The possibilities of using IL-32 as an airway inflammation biomarker and an
asthma therapeutic agent are also evaluated.
PMID- 29940982
TI - Antimicrobial misuse in pediatric urinary tract infections: recurrences and renal
scarring.
AB - BACKGROUND: In children, urinary tract infection (UTI) is one of a common
bacterial infection. This study was conducted to detect the uropathogen,
antimicrobial susceptibility, pathogen associated with recurrences and renal
scarring in children initially taken care from general practitioners and later
presented to tertiary care. METHODS: Every inward UTI episode, culture and
antimicrobial susceptibility was done while on past 6-month, history of
infections and use of antimicrobials was collected using clinical records and
demonstration of antimicrobials. Children with recurrent pyelonephritis was
followed and in vitro bio film formation was assessed. RESULTS: Frequency of UTI
was significantly high among infants (p = 0.03). Last 6-month, all (220) were
exposed to antimicrobials. Cefixime was the commonly prescribed antimicrobial (p
= 0.02). In current UTI episode, 64.5% (142/220) of children with UTI were
consulted GPs' prior to seek treatment from tertiary care pediatric unit (p =
0.02). While on follow up child who developed UTI, found urine culture isolates
were significantly shifted from E. coli and K. pneumoniae to extended spectrum of
beta-lactamase (ESBL) E. coli and K. pneumoniae. Out of 208 participants, 36 of
them had re-current pyelonephritis (R-PN). Renal scarring (RS) was detected in 22
out of 70 patients with pyelonephritis following dimercaptosuccinic acid scan.
Following each episodes of recurrent pyelonephritis 11% of new scar formation was
detected (p = 0.02). Bio film forming E. coli and K. pneumoniae was significantly
associated in patients with R-PN (p = 0.04). DISCUSSION: Medical care providers
often prescribe antimicrobials without having an etiological diagnosis. While
continuing exposure of third generation cephalosporin and carbapenem leads to
development of ESBL and CRE microbes in great. The empiric uses of antimicrobials
need to be stream lined with local epidemiology and antimicrobial susceptibility
pattern. R-PN in childhood leads to RS. In great, bio film formation act as the
focus for such recurrences.
PMID- 29940983
TI - Published analysis of contraceptive effectiveness of Daysy and DaysyView app is
fatally flawed.
AB - BACKGROUND: In March 2018, Dr. Martin C. Koch and colleagues published an
analysis purporting to measure the effectiveness of the Daysy device and
DaysyView app for the prevention of unintended pregnancy. Unfortunately, the
analysis was flawed in multiple ways which render the estimates unreliable.
Unreliable estimates of contraceptive effectiveness can endanger public health.
MAIN BODY: This commentary details multiple concerns pertaining to the collection
and analysis of data in Koch et al. 2018. A key concern pertains to the
inappropriate exclusion of all women with fewer than 13 cycles of use from the
Pearl Index calculations, which has no basis in standard effectiveness
calculations. Multiple additional methodological concerns, as well as prior
attempts to directly convey concerns to the manufacturer regarding marketing
materials based on prior inaccurate analyses, are also discussed. CONCLUSION: The
Koch et al. 2018 publication produced unreliable estimates of contraceptive
effectiveness for the Daysy device and DaysyView app, which are likely
substantially higher than the actual contraceptive effectiveness of the device
and app. Those estimates are being used in marketing materials which may
inappropriately inflate consumer confidence and leave consumers more vulnerable
than expected to the risk of unintended pregnancy. Prior attempts to directly
convey concerns to the manufacturer of this device were unsuccessful in
preventing publication of subsequent inaccurate analyses. To protect public
health, concerns with this analysis should be documented in the published
literature, the Koch et al. 2018 analysis should be retracted, and marketing
materials on contraceptive effectiveness should be subjected to appropriate
oversight.
PMID- 29940984
TI - Clinical evaluation of intensity-modulated radiotherapy for locally advanced
pancreatic cancer.
AB - BACKGROUND: The purpose was to retrospectively evaluate the effect of intensity
modulated radiotherapy (IMRT) on gastrointestinal (GI) toxicities and outcomes
compared to three-dimensional conformal radiotherapy (3DCRT) for locally advanced
pancreatic cancer (LAPC). METHODS: We included 107 consecutive patients who
underwent CRT for LAPC from September 2001 to March 2015; 80 patients underwent
3DCRT and 27 patients underwent IMRT. They were compared for GI toxicities,
locoregional progression free survival (LRPFS), distant metastasis free survival
(DMS), and overall survival (OS). RESULTS: Median radiation dose and fractions
for 3DCRT and IMRT were 54 Gy/30 fr. and 48 Gy/15 fr. The regimens of CRT
consisted of weekly gemcitabine 250 mg/m2 (for 3DCRT) or 1000 mg/m2 (for IMRT).
Acute GI toxicity >=grade 2 occurred in 32 patients (40%) treated with 3DCRT
compared with five patients (19%) treated with IMRT. Late GI toxicity of grade 3
occurred in 10 patients (12%) treated with 3DCRT and one patient (4%) treated
with IMRT. Patients who underwent IMRT had superior 1-year LRPFS (73.1% vs.
63.2%, p = 0.035) and 1-year OS (92.3% vs. 68.2%, p = 0.037) as compared with
those treated with 3DCRT. Multivariate analysis showed that in IMRT patients,
higher dose (>=45 Gy) was an independent factor for better LRPFS and OS.
CONCLUSIONS: LAPC patients treated with hypofractionated full-dose gemcitabine
IMRT had improved OS and LRPFS without increased GI toxicities when compared to
those of patients treated with conventionally fractionated low dose gemcitabine
3DCRT. In IMRT patients, higher dose was an independent favorable prognostic
factor for better LRPFS and OS, which suggests that dose escalation with IMRT for
LAPC is a promising strategy.
PMID- 29940985
TI - Surgical management of chronic lateral ankle instability: a meta-analysis.
AB - BACKGROUND: A key point to surgical treatment of chronic lateral ankle
instability is choosing a suitable surgical procedure. The purpose of this meta
analysis was to compare different surgical techniques for management of chronic
lateral ankle instability. METHODS: We searched the Cochrane Library, MEDLINE,
and EMBASE. All identified randomized and quasi-randomized controlled trials of
operative treatment for chronic lateral ankle instability were included. Two
review authors independently extracted data from each study and assessed risk of
bias. Where appropriate, results of comparable studies were pooled. RESULTS:
Seven randomized controlled trials were included for analysis. They fell in five
clearly distinct groups. One study comparing two different kinds of non-anatomic
reconstruction procedures (dynamic and static tenodesis) found two clinical
outcomes favoring static tenodesis: better clinical satisfaction and fewer
subsequent sprains. Two studies compared non-anatomic reconstruction versus
anatomic repairment. In one study, nerve damage was more frequent in non-anatomic
reconstruction group; the other one reported that radiological measurement of
ankle laxity showed that non-anatomic reconstruction provided higher reduction of
talar tilt angle. Two studies comparing two anatomic repairment surgical
techniques (transosseous suture versus imbrication) showed no significant
difference in any clinical outcome at the follow-up except operation time. One
study compared two different anatomic repairment techniques. They found that the
double anchor technique was superior with respect to the reduction of talar tilt
than single anchor technique. One study compared an anatomic reconstruction
procedure with a modified Brostrom technique. Primary reconstruction combined
with ligament advanced reinforcement system results in better patient-scored
clinical outcome, at 2 years post-surgery, than the modified Brostrom procedure.
CONCLUSIONS: There is limited evidence to support any one surgical technique over
another surgical technique for chronic lateral ankle instability, but based on
the evidence, we could still get some conclusions: (1) There are limitations to
the use of dynamic tenodesis, which obtained poor clinical satisfaction and more
subsequent sprains. (2) Non-anatomic reconstruction abnormally increased
inversion stiffness at the subtalar level as compare with anatomic repairment.
(3) Multiple types of modified Brostrom procedures could acquire good clinical
results. (4) Anatomic reconstruction is a better procedure for some specific
patients.
PMID- 29940986
TI - Practice-based skill acquisition of pushrim-activated power-assisted wheelchair
propulsion versus regular handrim propulsion in novices.
AB - BACKGROUND: Regular handrim wheelchair (RHW) propulsion is straining for the
upper extremities and wheelchair users often experience overuse problems. A
recent advancement in wheelchair technology that could assist users is the
pushrim-activated power-assisted wheelchair (PAPAW). PAPAWs are challenging to
control, yet it is unclear how people learn to use a PAPAW. The purpose of this
study is to examine early skill acquisition through practice in PAPAWs and
compare it with RHWs. METHODS: Twenty-four able-bodied novices were randomly
allocated to either the RHW group or the PAPAW group. The experiment consisted of
five sessions with three blocks of 4 min steady-state practice at 1.11 m/s and
0.21 W/kg. Finally, a transfer to the other mode was made. Data were collected
with a drag-test, breath-by-breath spirometry, and a motion capture system. The
last minute of each four-minute block was used for analysis. A mixed analysis of
variance (ANOVA) was used to test for group, time, and interaction effects.
RESULTS: Both groups improved their (assisted) mechanical efficiency, reduced
their stroke rate, right-left and forward-backward deviation on the treadmill,
and had a lower rate of perceived exertion (RPE) over time. (Assisted) mechanical
efficiency was higher for the PAPAW group than for the RHW group and RPE was
lower. However, left-right and forward-backward deviation was also found to be
higher in the PAPAW group. CONCLUSIONS: At the group level the energetic cost of
RHW and PAPAW propulsion can be lowered through low-intensity practice in novice
users. The PAPAW is more 'efficient' than the RHW given the reduced energy
requirement of the user from the motor assist, but more difficult to control.
Future studies on PAPAWs should focus on the control needs of the user and their
interaction with the power-assist technology.
PMID- 29940988
TI - Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by
augmenting SGK3/GSK-3beta/beta-catenin signalling.
AB - BACKGROUND: Serum and glucocorticoid-regulated kinase 3 (SGK3) has been reported
to play an important role in tumour progression, but its role in cancer stem
cells (CSCs) remains obscure. The phosphoinositide 3-kinase (PI3K) pathway is
considered a hallmark of cancer. Although many PI3K pathway-targeted therapies
have been tested in oncology trials, the results are not satisfactory. METHODS:
We used spheroids cultured in serum-free culture medium and MicroBead isolation
to obtain liver CSCs. Spheroid formation assay and flow cytometric analysis were
performed to investigate liver CSC expansion. Real-time polymerase chain reaction
(PCR), western blot and immunofluorescence were used to assess gene expression in
cell lines. RESULTS: We found that SGK3 is preferentially activated in liver
CSCs. Upregulated SGK3 significantly increases the expansion of liver CSCs.
Conversely, suppression of SGK3 in human hepatocarcinoma (HCC) cells had an
opposite effect. Mechanistically, SGK3 promoted beta-catenin accumulation by
suppressing GSK-3beta-mediated beta-catenin degradation in liver CSCs, and then
promoting the expansion of liver CSCs. Prolonged treatment of HCC cells with
class I PI3K inhibitors leads to activation of SGK3 and expansion of liver CSCs.
Inhibition of hVps34 can block SGK3 activity and suppress liver CSC expansion
induced by PI3K inhibitors. More importantly, we also found that prolonged
treatment of HCC cells with PI3K inhibitors stimulates the beta-catenin
signalling pathway via activation of SGK3. CONCLUSIONS: Prolonged inhibition of
class I PI3K promotes liver CSC expansion by augmenting SGK3-dependent beta
catenin stabilisation, and effective inhibition of SGK3 signalling may be useful
in eliminating liver CSCs and in PI3K pathway-targeted cancer therapies.
PMID- 29940989
TI - Linking molar organizational climate and strategic implementation climate to
clinicians' use of evidence-based psychotherapy techniques: cross-sectional and
lagged analyses from a 2-year observational study.
AB - BACKGROUND: Behavioral health organizations are characterized by multiple
organizational climates, including molar climate, which encompasses clinicians'
shared perceptions of how the work environment impacts their personal well-being,
and strategic implementation climate, which includes clinicians' shared
perceptions of the extent to which evidence-based practice implementation is
expected, supported, and rewarded by the organization. Theory suggests these
climates have joint, cross-level effects on clinicians' implementation of
evidence-based practice and that these effects may be long term (i.e., up to 2
years); however, no empirical studies have tested these relationships. We
hypothesize that molar climate moderates implementation climate's concurrent and
long-term relationships with clinicians' use of evidence-based practice such that
strategic implementation climate will have its most positive effects when it is
accompanied by a positive molar climate. METHODS: Hypotheses were tested using
data collected from 235 clinicians in 20 behavioral health organizations. At
baseline, clinicians reported on molar climate and implementation climate. At
baseline and at a 2-year follow-up, all clinicians who were present in the
organizations reported on their use of cognitive-behavioral psychotherapy
techniques, an evidence-based practice for youth psychiatric disorders. Two-level
mixed-effects regression models tested whether baseline molar climate and
implementation climate interacted in predicting clinicians' evidence-based
practice use at baseline and at 2-year follow-up. RESULTS: In organizations with
more positive molar climates at baseline, higher levels of implementation climate
predicted increased evidence-based practice use among clinicians who were present
at baseline and among clinicians who were present in the organizations at 2-year
follow-up; however, in organizations with less positive molar climates,
implementation climate was not related to clinicians' use of evidence-based
practice at either time point. CONCLUSIONS: Optimizing clinicians' implementation
of evidence-based practice in behavioral health requires attention to both molar
climate and strategic implementation climate. Strategies that focus exclusively
on implementation climate may not be effective levers for behavior change if the
organization does not also engender a positive molar climate. These findings have
implications for the development of implementation theory and effective
implementation strategies.
PMID- 29940987
TI - Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the
wild side.
AB - Oxidative stress is related to ageing and degenerative diseases, including
cancer. However, a moderate amount of reactive oxygen species (ROS) is required
for the regulation of cellular signalling and gene expression. A low level of ROS
is important for maintaining quiescence and the differentiation potential of
haematopoietic stem cells (HSCs), whereas the level of ROS increases during
haematopoietic differentiation; thus, suggesting the importance of redox
signalling in haematopoiesis. Here, we will analyse the importance of ROS for
haematopoiesis and include evidence showing that cells from leukaemia patients
live under oxidative stress. The potential sources of ROS will be described.
Finally, the level of oxidative stress in leukaemic cells can also be harnessed
for therapeutic purposes. In this regard, the reliance of front-line anti
leukaemia chemotherapeutics on increased levels of ROS for their mechanism of
action, as well as the active search for novel compounds that modulate the redox
state of leukaemic cells, will be analysed.
PMID- 29940991
TI - Decoding the grasping intention from electromyography during reaching motions.
AB - BACKGROUND: Active upper-limb prostheses are used to restore important hand
functionalities, such as grasping. In conventional approaches, a pattern
recognition system is trained over a number of static grasping gestures. However,
training a classifier in a static position results in lower classification
accuracy when performing dynamic motions, such as reach-to-grasp. We propose an
electromyography-based learning approach that decodes the grasping intention
during the reaching motion, leading to a faster and more natural response of the
prosthesis. METHODS AND RESULTS: Eight able-bodied subjects and four individuals
with transradial amputation gave informed consent and participated in our study.
All the subjects performed reach-to-grasp motions for five grasp types, while the
elecromyographic (EMG) activity and the extension of the arm were recorded. We
separated the reach-to-grasp motion into three phases, with respect to the
extension of the arm. A multivariate analysis of variance (MANOVA) on the
muscular activity revealed significant differences among the motion phases.
Additionally, we examined the classification performance on these phases. We
compared the performance of three different pattern recognition methods; Linear
Discriminant Analysis (LDA), Support Vector Machines (SVM) with linear and non
linear kernels, and an Echo State Network (ESN) approach. Our off-line analysis
shows that it is possible to have high classification performance above 80%
before the end of the motion when with three-grasp types. An on-line evaluation
with an upper-limb prosthesis shows that the inclusion of the reaching motion in
the training of the classifier importantly improves classification accuracy and
enables the detection of grasp intention early in the reaching motion.
CONCLUSIONS: This method offers a more natural and intuitive control of
prosthetic devices, as it will enable controlling grasp closure in synergy with
the reaching motion. This work contributes to the decrease of delays between the
user's intention and the device response and improves the coordination of the
device with the motion of the arm.
PMID- 29940990
TI - The role of point of care ultrasound in prehospital critical care: a systematic
review.
AB - BACKGROUND: In 2011, the role of Point of Care Ultrasound (POCUS) was defined as
one of the top five research priorities in physician-provided prehospital
critical care and future research topics were proposed; the feasibility of
prehospital POCUS, changes in patient management induced by POCUS and education
of providers. This systematic review aimed to assess these three topics by
including studies examining all kinds of prehospital patients undergoing all
kinds of prehospital POCUS examinations and studies examining any kind of POCUS
education in prehospital critical care providers. METHODS AND RESULTS: By a
systematic literature search in MEDLINE, EMBASE, and Cochrane databases, we
identified and screened titles and abstracts of 3264 studies published from 2012
to 2017. Of these, 65 studies were read in full-text for assessment of
eligibility and 27 studies were ultimately included and assessed for quality by
SIGN-50 checklists. No studies compared patient outcome with and without
prehospital POCUS. Four studies of acceptable quality demonstrated feasibility
and changes in patient management in trauma. Two studies of acceptable quality
demonstrated feasibility and changes in patient management in breathing
difficulties. Four studies of acceptable quality demonstrated feasibility,
outcome prediction and changes in patient management in cardiac arrest, but also
that POCUS may prolong pauses in compressions. Two studies of acceptable quality
demonstrated that short (few hours) teaching sessions are sufficient for
obtaining simple interpretation skills, but not image acquisition skills. Three
studies of acceptable quality demonstrated that longer one- or two-day courses
including hands-on training are sufficient for learning simple, but not advanced,
image acquisition skills. Three studies of acceptable quality demonstrated that
systematic educational programs including supervised examinations are sufficient
for learning advanced image acquisition skills in healthy volunteers, but that
more than 50 clinical examinations are required for expertise in a clinical
setting. CONCLUSION: Prehospital POCUS is feasible and changes patient management
in trauma, breathing difficulties and cardiac arrest, but it is unknown if this
improves outcome. Expertise in POCUS requires extensive training by a combination
of theory, hands-on training and a substantial amount of clinical examinations -
a large part of these needs to be supervised.
PMID- 29940992
TI - Using information communication technology in models of integrated community
based primary health care: learning from the iCOACH case studies.
AB - BACKGROUND: Information communication technology (ICT) is a critical enabler of
integrated models of community-based primary health care; however, little is
known about how existing technologies have been used to support new models of
integrated care. To address this gap, we draw on data from an international study
of integrated models, exploring how ICT is used to support activities of
integrated care and the organizational and environmental barriers and enablers to
its adoption. METHODS: We take an embedded comparative multiple-case study
approach using data from a study of implementation of nine models of integrated
community-based primary health care, the Implementing Integrated Care for Older
Adults with Complex Health Needs (iCOACH) study. Six cases from Canada, three
each in Ontario and Quebec, and three in New Zealand, were studied. As part of
the case studies, interviews were conducted with managers and front-line health
care providers from February 2015 to March 2017. A qualitative descriptive
approach was used to code data from 137 interviews and generate word tables to
guide analysis. RESULTS: Despite different models and contexts, we found
strikingly similar accounts of the types of activities supported through ICT
systems in each of the cases. ICT systems were used most frequently to support
activities like care coordination by inter-professional teams through information
sharing. However, providers were limited in their ability to efficiently share
patient data due to data access issues across organizational and professional
boundaries and due to system functionality limitations, such as a lack of
interoperability. CONCLUSIONS: Even in innovative models of care, managers and
providers in our cases mainly use technology to enable traditional ways of
working. Technology limitations prevent more innovative uses of technology that
could support disruption necessary to improve care delivery. We argue the
barriers to more innovative use of technology are linked to three factors: (1)
information access barriers, (2) limited functionality of available technology,
and (3) organizational and provider inertia.
PMID- 29940993
TI - The EZ-blocker for one-lung ventilation in patients undergoing thoracic surgery:
clinical applications and experience in 100 cases in a routine clinical setting.
AB - BACKGROUND: In certain clinical situations the insertion of a double-lumen tube
(DLT) for one-lung ventilation (OLV) is not feasible or unfavorable. In these
cases, the EZ-Blocker (EZB) may serve as an alternative. The aim of our analysis
was to report on the clinical applications and our experience with the EZB for
one-lung ventilation in 100 patients undergoing thoracic surgery. METHODS: All
anesthetic records from patients older than 18 years of age undergoing general
anesthesia in the department of thoracic surgery with intraoperative use of an
EZB for OLV at the University Hospital of Erlangen in four consecutive years were
analyzed retrospectively. RESULTS: Most frequently, EZB was used in difficult
airway (27%) and for surgical procedures with high risk for left recurrent
laryngeal nerve injury (21%), followed by application in intubated (12%) or
tracheostomized (11%) patients. 11% of the patients had an increased risk of
gastric regurgitation. Almost all EZBs were placed free of complications (99%).
Clinically sufficient lung collapse was achieved in all patients. No serious
airway injuries or immediate complications were documented. CONCLUSIONS: The EZB
is an efficient, easy-to-use and safe airway device and enables OLV in several
clinical situations, when conventional DLTs are not feasible or less favorable.
Three major applications were depicted from the data: expected difficult airway,
surgical procedures with necessity of intraoperative recurrent laryngeal nerve
monitoring and already intubated or tracheostomized patients.
PMID- 29940994
TI - NS3 Protein from Rice stripe virus affects the expression of endogenous genes in
Nicotiana benthamiana.
AB - BACKGROUND: Rice stripe virus (RSV) belongs to the genus Tenuivirus. It is
transmitted by small brown planthoppers in a persistent and circulative
propagative manner and causes rice stripe disease (RSD). The NS3 protein of RSV,
encoded by the viral strand of RNA3, is a viral suppressor of RNA silencing
(VSR). NS3 plays a significant role in viral infection, and NS3-transgenic plants
manifest resistance to the virus. METHODS: The stability and availability of NS3
produced by transgenic Nicotiana benthamiana was investigated by northern blot
analysis. The accumulation of virus was detected by western blot analysis.
Transcriptome sequencing was used to identify differentially expressed genes
(DEGs) in NS3-transgenic N. benthamiana. RESULTS: When the host plants were
inoculated with RSV, symptoms and viral accumulation in NS3-transgenic N.
benthamiana were reduced compared with the wild type. Transcriptome analysis
identified 2533 differentially expressed genes (DEGs) in the NS3-transgenic N.
benthamiana, including 597 upregulated genes and 1936 downregulated genes. These
DEGs were classified into three Gene Ontology (GO) categories and were associated
with 43 GO terms. KEGG pathway analysis revealed that these DEGs were involved in
pathways associated with ribosomes (ko03010), photosynthesis (ko00195),
photosynthesis-antenna proteins (ko00196), and carbon metabolism (ko01200). More
than 70 DEGs were in these four pathways. Twelve DEGs were selected for RT-qPCR
verification and subsequent analysis. The results showed that NS3 induced host
resistance by affecting host gene expression. CONCLUSION: NS3, which plays dual
roles in the process of infection, may act as a VSR during RSV infection, and
enable viral resistance in transgenic host plants. NS3 from RSV affects the
expression of genes associated with ribosomes, photosynthesis, and carbon
metabolism in N. benthamiana. This study enhances our understanding of the
interactions between VSRs and host plants.
PMID- 29940995
TI - Prevalence of human pathogenic Yersinia enterocolitica in Swedish pig farms.
AB - BACKGROUND: Pigs are the most important reservoir for human pathogenic Yersinia
enterocolitica. We investigated the herd prevalence of human pathogenic Y.
enterocolitica in Swedish pig farms by analysing pen faecal samples using a cold
enrichment of 1 week and thereafter subsequent plating onto chromogenic selective
media (CAY agar). RESULTS: Pathogenic Y. enterocolitica was found in 32 (30.5%)
of the 105 sampled farms with finisher pigs. Bioserotype 4/O:3 was identified at
all but one farm, where 2/O:9 was identified. Pen-prevalence within the positive
herds varied from 1/4 to 4/4 pens. The calculated intra-class correlation
coefficient ICC (0.89) from a model with a random effect for grouping within herd
indicated a very high degree of clustering by herd. None of the explored risk
factors, including herd size, herd type, pig flow, feed type, access to outdoors,
evidence of birds and rodents in the herd, usage of straw, number of pigs in
sampled pen and age of pigs in pen were significantly associated with Y.
enterocolitica status of the pen. The use of high pressure washing with cold
water was significantly associated with Y. enterocolitica in the pen (OR = 84.77,
4.05-1772). Two culture methods were assessed for detection of Y. enterocolitica,
one of which included the use of a chromogenic agar (CAY agar) intended for
detection of human pathogenic Y. enterocolitica. The chromogenic media was found
equal or superior to traditional methods and was used in this study. The isolates
obtained were characterised by biotyping, serotyping, mass spectrometry (MALDI
TOF) and PCR. Characterisation by MALDI-TOF gave identical results to that of
conventional bioserotyping. All porcine isolates were positive for the ail and
inv genes by PCR, indicating that the isolates were most likely pathogenic to
humans. CONCLUSIONS: Human pathogenic Y. enterocolitica was found in nearly one
third of the Swedish pig farms with finisher pigs. The use of high pressure
washing with cold water was associated with the presence of Y. enterocolitica in
the pen. A modified culturing method using a chromogenic agar was efficient for
detection of pathogenic Y. enterocolitica in pig faeces. The use of
masspectrometry for identification and subtyping was in agreement with
conventional biotyping and serotyping methods.
PMID- 29940996
TI - There might be blood: a scoping review on women's responses to contraceptive
induced menstrual bleeding changes.
AB - INTRODUCTION: Concern about side effects and health issues are common reasons for
contraceptive non-use or discontinuation. Contraceptive-induced menstrual
bleeding changes (CIMBCs) are linked to these concerns. Research on women's
responses to CIMBCs has not been mapped or summarized in a systematic scoping
review. METHODS: We conducted a systematic scoping review of data on women's
responses to CIMBCs in peer-reviewed, English-language publications in the last
15 years. Investigator dyads abstracted information from relevant studies on pre
specified and emergent themes using a standardized form. We held an expert
consultation to obtain critical input. We provide recommendations for
researchers, contraceptive counselors, and product developers. RESULTS: We
identified 100 relevant studies. All world regions were represented (except
Antarctica), including Africa (11%), the Americas (32%), Asia (7%), Europe (20%),
and Oceania (6%). We summarize findings pertinent to five thematic areas: women's
responses to contraceptive-induced non-standard bleeding patterns; CIMBCs
influence on non-use, dissatisfaction or discontinuation; conceptual linkages
between CIMBCs and health; women's responses to menstrual suppression; and other
emergent themes. Women's preferences for non-monthly bleeding patterns ranged
widely, though amenorrhea appears most acceptable in the Americas and Europe.
Multiple studies reported CIMBCs as top reasons for contraceptive dissatisfaction
and discontinuation; others suggested disruption of regular bleeding patterns was
associated with non-use. CIMBCs in some contexts were perceived as linked with a
wide range of health concerns; e.g., some women perceived amenorrhea to cause a
buildup of "dirty" or "blocked" blood, in turn perceived as causing blood clots,
fibroids, emotional disturbances, weight gain, infertility, or death. Multiple
studies addressed how CIMBCs (or menstruation) impacted daily activities,
including participation in domestic, work, school, sports, or religious life;
sexual or emotional relationships; and other domains. CONCLUSIONS: Substantial
variability exists around how women respond to CIMBCs; these responses are shaped
by individual and social influences. Despite variation in responses across
contexts and sub-populations, CIMBCs can impact multiple aspects of women's
lives. Women's responses to CIMBCs should be recognized as a key issue in
contraceptive research, counseling, and product development, but may be
underappreciated, despite likely - and potentially substantial - impacts on
contraceptive discontinuation and unmet need for modern contraception.
PMID- 29940997
TI - Pathophysiology of carotid-cavernous fistulas in vascular Ehlers-Danlos syndrome:
a retrospective cohort and comprehensive review.
AB - BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is a rare condition
characterized by connective tissue fragility. Direct spontaneous carotid
cavernous fistula (sCCF) is reportedly pathognomonic of vEDS. We conducted this
study to understand the possible mechanisms of occurrence of sCCF in this subset
of patients. METHODS: We conducted a retrospective analysis of a monocentric vEDS
cohort along with a literature review regarding sCCF in this condition. RESULTS:
Of 133 patients regularly followed in our centre between 2000 and 2017, 13 (9.8%)
had a diagnosis of direct sCCF (92.3% female, median age 33.0 years,
interquartile range (IQR) [26.0-39.5]). There were 7 Glycine missense and 6
splice-site variants but no variant leading to haploinsufficiency. The literature
search identified 97 vEDS patients with direct sCCF (79.4% female, 7.2% sex not
reported, median age 31.0 years, IQR [24.0-39.0]). Increased carotid
circumferential wall stress, higher carotid distensibility and lower carotid
intima-media thickness could contribute to a higher risk for direct sCCF in vEDS.
There is no predictive factor for the occurrence of sCCF apart from female sex in
vEDS. CONCLUSIONS: In vEDS, anatomical and pathophysiological features of the
intra-cavernous internal carotid artery make it prone to shunting in the
cavernous sinus, due either to a spontaneous rupture or to a spontaneous
dissection with pseudoaneurysm formation. Direct sCCF in seemingly healthy young
individuals should be highly suggestive of vEDS and prompt further investigation.
PMID- 29940998
TI - ER-alpha36 mediates cisplatin resistance in breast cancer cells through EGFR/HER
2/ERK signaling pathway.
AB - BACKGROUND: ER-alpha36, a novel ER-alpha66 variant, has been demonstrated to
promote tamoxifen resistance in breast cancer cells. However, the role and
mechanisms of ER-alpha36 in cisplatin resistance of breast cancer cells remain
unclear. This study investigates the expression and role of ER-alpha36 in
cisplatin resistance of breast cancer cells and elucidates its underlying
mechanisms. METHODS: The expression of ER-alpha36 and the proteins involved in
nongenomic estrogen signaling was evaluated by western blot analysis. Cisplatin
sensitivity was explored by CCK-8 assay, monolayer colony formation assay and
apoptosis assays, respectively. ER-alpha36 siRNAs/shRNAs and overexpression
vector were transfected into cells to down-regulate or up-regulate ER-alpha36
expression. Loss-and gain-of function assays were performed to investigate the
role of ER-alpha36 in cisplatin sensitivity. The interaction between ER-alpha36
and EGFR/HER-2 were detected using CoIP. A mouse xenograft model of breast cancer
was established to verify the role of ER-alpha36 in vivo. RESULTS: ER-alpha36 is
expressed at higher levels in cisplatin-resistant breast cancer cells compared to
cisplatin sensitive cells. Cisplatin induced up-regulation of ER-alpha36 in a
dose-dependent manner in breast cancer cells. Overexpression of ER-alpha36 leaded
to cell resistant to cisplatin and knockdown of ER-alpha36 in cisplatin-resistant
breast cancer cells restored cisplatin sensitivity. The up-regulation of ER
alpha36 resulted in increased activation of nongenomic estrogen signaling, which
was responsible for cisplatin resistance. Disruption of ER-alpha36-mediated
nongenomic estrogen signaling with kinase inhibitors significantly inhibited
cisplatin-induced expression of ER-alpha36 and increased cisplatin sensitivity.
The in vivo experiment also confirmed that up-regulation of ER-alpha36 attenuated
cisplatin sensitivity in a mouse xenograft model of breast cancer. CONCLUSIONS:
The results for the first time demonstrated that ER-alpha36 mediates cisplatin
resistance in breast cancer cells through nongenomic estrogen signaling,
suggesting that ER-alpha36 may serve as a novel target for cisplatin resistance
and a potential indicator of cisplatin sensitivity in breast cancer treatment.
PMID- 29940999
TI - Thymectomy in nonthymomatous myasthenia gravis - systematic review and meta
analysis.
AB - BACKGROUND: The objective of this study is to evaluate by means of a systematic
review, the efficacy of thymectomy as compared to medical treatment for non
thymomatous myasthenia gravis (MG). METHODS: Medline, Embase, and Lilacs were
searched for experimental and observational studies that compared non-surgical
(drug therapy) and surgical treatment of non-thymomatous MG (thymectomy performed
by the transsternal approach). Inclusion criteria were: studies that compared the
two types of treatment and had at least 10 adult patients in each group.
Exclusion criteria were articles published before 1970, as well as those that
included patients treated before 1950. The outcomes evaluated were: remission,
and improvement rates. RevMan 5.3 software provided by the Cochrane Collaboration
was used. When the heterogeneity between the studies was greater than 75%, a meta
analysis was not performed according to RevMan guidelines. RESULTS: The total
number of patients evaluated in 19 articles selected was 5841 (2911 surgical and
2930 non-surgical). Two included randomized clinical trials showed superiority of
the surgical treatment over the non-surgical. Four retrospective studies with 379
patients paired by gender, age, and other confounders, also showed superiority of
surgical treatment (OR 4.10, 95% CI 2.25 to 7.44; I2 = 20%). In meta-analyses,
remission assessed in 17 studies (5686 patients) was greater in patients who
underwent surgical treatment (OR 2.34, 95% CI 1.79 to 3.05; I2 = 56%). For
improvement assessed in 13 studies (3063 patients) were not appropriate to carry
out the meta-analysis due to the high heterogeneity among the studies in the
outcome (87%). CONCLUSION: Thymectomy may be considered effective in the
treatment for non-thymomatous MG, with remission rate higher than for non
surgical treatment.
PMID- 29941000
TI - Accommodating quality and service improvement research within existing ethical
principles.
AB - BACKGROUND: Quality and service improvement (QSI) research employs a broad range
of methods to enhance the efficiency of healthcare delivery. QSI research differs
from traditional healthcare research and poses unique ethical questions. Since
QSI research aims to generate knowledge to enhance quality improvement efforts,
should it be considered research for regulatory purposes? Is review by a research
ethics committee required? Should healthcare providers be considered research
participants? If participation in QSI research entails no more than minimal risk,
is consent required? The lack of consensus on answers to these questions
highlights the need for ethical guidance. MAIN BODY: Three distinct approaches to
classifying QSI research in accordance with existing ethical principles and
regulations can be found in the literature. In the first approach, QSI research
is viewed as distinct from other types of healthcare research and does not
require regulation. In the second approach, QSI research falls within regulatory
guidelines but is exempt from research ethics committee review. In the third
approach, QSI research is deemed to be part of the learning healthcare system
and, as such, is subject to a different set of ethical principles entirely. In
this paper, we critically assess each of these views. CONCLUSION: While none of
these approaches is entirely satisfactory, we argue that use of the ethical
principles governing research provides the best means of addressing the numerous
questions posed by QSI research.
PMID- 29941001
TI - Ambient fine particulate matter exposure induces reversible cardiac dysfunction
and fibrosis in juvenile and older female mice.
AB - BACKGROUND: Cardiovascular disease is the leading cause of mortality in the
advanced world, and age is an important determinant of cardiac function. The
purpose of the study is to determine whether the PM2.5-induced cardiac
dysfunction is age-dependent and whether the adverse effects can be restored
after PM2.5 exposure withdrawal. METHODS: Female C57BL/6 mice at different ages
(4-week-old, 4-month-old, and 10-month-old) received oropharyngeal aspiration of
3 mg/kg b.w. PM2.5 every other day for 4 weeks. Then, 10-month-old and 4-week-old
mice were exposed to PM2.5 for 4 weeks and withdrawal PM2.5 1 or 2 weeks. Heart
rate and systolic blood pressure were measured using a tail-cuff system. Cardiac
function was assessed by echocardiography. Left ventricles were processed for
histology to assess myocardial fibrosis. ROS generation was detected by
photocatalysis using 2',7'-dichlorodihydrofluorescein diacetate (DCFHDA). The
expression of cardiac fibrosis markers (Col1a1, Col3a1) and possible signaling
molecules, including NADPH oxidase 4 (NOX-4), transforming growth factor beta1
(TGFbeta1), and Smad3, were detected by qPCR and/ or Western blot. RESULTS: PM2.5
exposure induced cardiac diastolic dysfunction of mice, elevated the heart rate
and blood pressure, developed cardiac systolic dysfunction of 10-month-old mice,
and caused fibrosis in both 4-week-old and 10-month-old mice. PM2.5 exposure
increased the expression of Col1a1, Col3a1, NOX-4, and TGFbeta1, activated Smad3,
and generated more reactive oxygen species in the myocardium of 4-week-old and 10
month-old mice. The withdrawal from PM2.5 exposure restored blood pressure, heart
rate, cardiac function, expression of collagens, and malonaldehyde (MDA) levels
in hearts of both 10-month-old and 4-week-old mice. CONCLUSION: Juvenile and
older mice are more sensitive to PM2.5 than adults and suffer from cardiac
dysfunction. PM2.5 exposure reversibly elevated heart rate and blood pressure,
induced cardiac systolic dysfunction of older mice, and reversibly induced
fibrosis in juvenile and older mice. The mechanism by which PM2.5 exposure
resulted in cardiac lesions might involve oxidative stress, NADPH oxidase,
TGFbeta1, and Smad-dependent pathways.
PMID- 29941002
TI - Liquid biopsy in mice bearing colorectal carcinoma xenografts: gateways
regulating the levels of circulating tumor DNA (ctDNA) and miRNA (ctmiRNA).
AB - BACKGROUND: Circulating tumor DNA (ctDNA) and miRNA (ctmiRNA) are promising
biomarkers for early tumor diagnosis, prognosis and monitoring, and to predict
therapeutic response. However, a clear understanding of the fine control on their
circulating levels is still lacking. METHODS: Three human colorectal carcinoma
cell lines were grown in culture and as tumor xenograft models in nude mice. Chip
based and droplet digital PCR platforms were used to systematically and
quantitatively assess the levels of DNAs and miRNAs released into the culture
supernatants and mouse blood plasma. RESULTS: Strikingly, mutated DNAs from the
same (KRAS) and different (PIK3CA and FBWX7) genomic loci were differentially
detected in culture supernatants and blood, with LS174T releasing 25 to 60 times
less DNA in culture, but giving rise to 7 to 8 times more DNA in blood than LoVo
cells. Greater LS174T ctDNA accumulation occurred in spite of similar CD31
immunostaining (micro-vascularization) and lesser proliferation and tissue
necrosis as compared to LoVo. As to the three selected miRNAs (miR-221, miR-222
and miR-141), all of them were constitutively present in the plasma of tumor-free
mice. Micro-RNA miR-141 was released into HT-29 cell supernatants 10 and 6.5
times less abundantly with respect to LoVo and LS174T, respectively; on the
contrary, release of miR-141 in blood of HT-29 xenografted mice was found similar
to that observed in LoVo and LS174T mice. CONCLUSIONS: Taken together, our
results support the existence of multiple, finely tuned (non-housekeeping)
control gateways that selectively regulate the release/accumulation of distinct
ctDNA and miRNA species in culture and tumor xenograft models. Different
xenografts (proxies of different patients) considerably differ in gateway usage,
adding several layers of complexity to the well-known idea of molecular
heterogeneity. We predict that even high tissue representation of mutated DNA and
miRNA may result in insufficient diagnostic analyte representation in blood. In
this respect, our data show that careful modeling in mice may considerably help
to alleviate complexity, for instance by pre-screening for the most abundant
circulating analytes in enlarged sets of tumor xenografts.
PMID- 29941003
TI - Speech-guided breathing retraining in asthma: a randomised controlled crossover
trial in real-life outpatient settings.
AB - BACKGROUND: Breathing retraining techniques have received increased attention in
the management of asthma, because there is growing evidence of the usefulness of
such methods in improving quality of life, reducing symptoms and reducing
bronchodilator use. Our study investigated the effect of anthroposophic
therapeutic speech (ATS), which uses sounds and syllabic rhythm to improve
articulation, breathing and cardiorespiratory interaction, in patients with
asthma in a real-life outpatient setting. METHODS: In a randomised controlled
crossover trial, patients with asthma in three centres in Switzerland and Germany
were randomised to either receive 11 ATS sessions or to wait. Subsequently,
patients changed either to wait or to receive ATS. Primary outcomes were changes
from the beginning to the end of each phase in the Asthma Quality of Life
Questionnaire (AQLQ) and spirometry parameters. Secondary outcomes were changes
in inhaled glucocorticoids, the Asthma Control Test (ACT), peak flow and asthma
exacerbations. RESULTS: Altogether, 63 patients were randomised, of which 56 were
enrolled and 49 completed the study. Statistically significant differences
between the ATS groups and waiting control groups were found for the overall AQLQ
score (d = 0.86, p = 0.001) and the domain scores for symptoms, activity
limitation and emotional function as well as ACT score (d = 0.53, p = 0.048). No
significant differences were observed in spirometry parameters, inhaled
glucocorticoids, peak flow and days without asthma exacerbation per week. No
serious adverse events occurred during ATS sessions. CONCLUSIONS: ATS
significantly improves asthma control and quality of life in patients with
asthma. Whether ATS may improve lung function remains to be shown. TRIAL
REGISTRATION: ClinicalTrials.gov NCT02501824 . Retrospectively registered on 8
July 2015.
PMID- 29941004
TI - CogStack - experiences of deploying integrated information retrieval and
extraction services in a large National Health Service Foundation Trust hospital.
AB - BACKGROUND: Traditional health information systems are generally devised to
support clinical data collection at the point of care. However, as the
significance of the modern information economy expands in scope and permeates the
healthcare domain, there is an increasing urgency for healthcare organisations to
offer information systems that address the expectations of clinicians,
researchers and the business intelligence community alike. Amongst other emergent
requirements, the principal unmet need might be defined as the 3R principle
(right data, right place, right time) to address deficiencies in organisational
data flow while retaining the strict information governance policies that apply
within the UK National Health Service (NHS). Here, we describe our work on
creating and deploying a low cost structured and unstructured information
retrieval and extraction architecture within King's College Hospital, the
management of governance concerns and the associated use cases and cost saving
opportunities that such components present. RESULTS: To date, our CogStack
architecture has processed over 300 million lines of clinical data, making it
available for internal service improvement projects at King's College London. On
generated data designed to simulate real world clinical text, our de
identification algorithm achieved up to 94% precision and up to 96% recall.
CONCLUSION: We describe a toolkit which we feel is of huge value to the UK (and
beyond) healthcare community. It is the only open source, easily deployable
solution designed for the UK healthcare environment, in a landscape populated by
expensive proprietary systems. Solutions such as these provide a crucial
foundation for the genomic revolution in medicine.
PMID- 29941005
TI - Increased extracellular matrix deposition during chondrogenic differentiation of
dental pulp stem cells from individuals with neurofibromatosis type 1: an in
vitro 2D and 3D study.
AB - BACKGROUND: Neurofibromatosis 1 (NF1) presents a wide range of clinical
manifestations, including bone alterations. Studies that seek to understand
cellular and molecular mechanisms underlying NF1 orthopedic problems are of great
importance to better understand the pathogenesis and the development of new
therapies. Dental pulp stem cells (DPSCs) are being used as an in vitro model for
several diseases and appear as a suitable model for NF1. The aim of this study
was to evaluate in vitro chondrogenic differentiation of DPSCs from individuals
with NF1 using two-dimensional (2D) and three-dimensional (3D) cultures. RESULTS:
To fulfill the criteria of the International Society for Cellular Therapy, DPSCs
were characterized by surface antigen expression and by their multipotentiality,
being induced to differentiate towards adipogenic, osteogenic, and chondrogenic
lineages in 2D cultures. Both DPSCs from individuals with NF1 (NF1 DPSCs) and
control cultures were positive for CD90, CD105, CD146 and negative for CD13,
CD14, CD45 and CD271, and successfully differentiated after the protocols.
Chondrogenic differentiation was evaluated in 2D and in 3D (pellet) cultures,
which were further evaluated by optical microscopy and transmission electron
microscopy (TEM). 2D cultures showed greater extracellular matrix deposition in
NF1 DPSCs comparing with controls during chondrogenic differentiation. In
semithin sections, control pellets hadhomogenous-sized intra and extracelullar
matrix vesicles, whereas NF1 cultures had matrix vesicles of different sizes. TEM
analysis showed higher amount of collagen fibers in NF1 cultures compared with
control cultures. CONCLUSION: NF1 DPSCs presented increased extracellular matrix
deposition during chondrogenic differentiation, which could be related to
skeletal changes in individuals with NF1.
PMID- 29941006
TI - Water/ethanol extract of Cucumis sativus L. fruit attenuates lipopolysaccharide
induced inflammatory response in endothelial cells.
AB - BACKGROUND: It is widely accepted the key role of endothelium in the onset of
many chronic and acute vascular and cardiovascular diseases. In the last decade,
traditional compounds utilized in "folk medicine" were considered with increasing
interest to discover new bioactive molecules potentially effective in a wide
range of diseases including cardiovascular ones. Since ancient times different
parts of the Cucumis sativus L. plant were utilized in Ayurvedic medicine, among
these, fruits were traditionally used to alleviate skin problem such as sunburn
irritation and inflammation. The main purpose of the present research was, in a
well-defined in vitro model of endothelial cells, to investigate whether a
water/ethanol extract of Cucumis sativus L. (CSE) fruit can attenuate the
damaging effect of pro-inflammatory lipopolysaccharide (LPS). METHODS: Cell
viability, gene expression of endothelial cell markers, cytokines secretion and
in vitro angiogenesis assay were performed on porcine Aortic Endothelial Cells
exposed to increasing doses (0.02; 02; 2 mg/ml) of CSE in the presence of pro
inflammatory lipopolysaccharide (LPS 10 MUg/ml). RESULTS: CSE reduced LPS-induced
cytotoxicity and decreased the cellular detachment, restoring the expression of
tight junction ZO-1. The increase of TLR4 expression induced by LPS was
counterbalanced by the presence of CSE, while the protective gene Hemeoxygenase
(HO)-1 was increased. Cucumis sativus L. inhibited the early robust secretion of
inflammatory IL-8 and GM-CSFs, furthermore inhibition of inflammatory IL-6 and IL
1alpha occurred late at 7 and 24 h respectively. On the contrary, the secretion
of anti-inflammatory IL-10, together with IL-18 and IFN-gamma was increased.
Moreover, the in vitro angiogenesis induced by inflammatory LPS was prevented by
the presence of Cucunis sativus L. extract, at any doses tested. CONCLUSIONS: Our
results have clearly demonstrated that Cucumis sativus L. extract has attenuated
lipopolysaccharide-induced inflammatory response in endothelial cells.
PMID- 29941008
TI - Design and implementation of an m-health data model for improving health
information access for reproductive and child health services in low resource
settings using a participatory action research approach.
AB - BACKGROUND: Information and Communication Technologies (ICTs) have been utilised
globally for advancing social and economic development. As information becomes
key to enlightening development initiatives, the role of mobile technology-based
ICT services is becoming more significant. The aim of this study was to design
and implement a mHealth data model with an intention of improving mothers'
knowledge of Reproductive and Child Health (RCH) services in rural environments
and to remind mothers who do not have access to mobile phones to attend antenatal
care. METHODS: The methodology adopted in this research was participatory action
research. A phased approach was utilised to answer the research question. The
phases were: diagnosis of the problem, action planning, action taking, evaluation
and reflection. The study was conducted in Chamwino district of Dodoma region,
Tanzania. Reproductive and Child Health sections of Buigiri dispensary and
Chamwino health centre were purposively selected. Data were collected through key
informant interviews, document review, focus group discussion and observation.
Content analysis methods were utilised during analysis. Consequently, the data
model was designed, implemented and evaluated. RESULTS: Challenges of information
dissemination in low resource settings noted in this study are: mobile phone
ownership and access of mothers, vertical coordination of health services and low
staffing levels of health workers. Mothers who do not own mobile phones can
leverage phone ownership of community leaders, TBAs, CHWs and relatives. This in
turn facilitates communication of health messages to mothers. CONCLUSIONS:
Although this study was conducted in a low resource setting, mobile network
coverage was good and thus SMS technology could be used. Research should be
conducted on how to disseminate similar information in remote areas without
mobile coverage.
PMID- 29941007
TI - The GUIDES checklist: development of a tool to improve the successful use of
guideline-based computerised clinical decision support.
AB - BACKGROUND: Computerised decision support (CDS) based on trustworthy clinical
guidelines is a key component of a learning healthcare system. Research shows
that the effectiveness of CDS is mixed. Multifaceted context, system,
recommendation and implementation factors may potentially affect the success of
CDS interventions. This paper describes the development of a checklist that is
intended to support professionals to implement CDS successfully. METHODS: We
developed the checklist through an iterative process that involved a systematic
review of evidence and frameworks, a synthesis of the success factors identified
in the review, feedback from an international expert panel that evaluated the
checklist in relation to a list of desirable framework attributes, consultations
with patients and healthcare consumers and pilot testing of the checklist.
RESULTS: We screened 5347 papers and selected 71 papers with relevant information
on success factors for guideline-based CDS. From the selected papers, we
developed a 16-factor checklist that is divided in four domains, i.e. the CDS
context, content, system and implementation domains. The panel of experts
evaluated the checklist positively as an instrument that could support people
implementing guideline-based CDS across a wide range of settings globally.
Patients and healthcare consumers identified guideline-based CDS as an important
quality improvement intervention and perceived the GUIDES checklist as a suitable
and useful strategy. CONCLUSIONS: The GUIDES checklist can support professionals
in considering the factors that affect the success of CDS interventions. It may
facilitate a deeper and more accurate understanding of the factors shaping CDS
effectiveness. Relying on a structured approach may prevent that important
factors are missed.
PMID- 29941010
TI - Targeting ERBB2 mutations in solid tumors: biological and clinical implications.
AB - Preclinical data have shown that ERBB2 activating mutations are responsive to
HER2 tyrosine kinase inhibitors. The aim of this study is to characterize the
landscape of ERBB2 mutations in solid tumors and the potential efficacy of ERBB2
targeting.We analyzed the next-generation sequencing results from 17,878 patients
with solid tumors and reported the outcome of 4 patients with advanced ERBB2
mutated tumors treated with a combination of trastuzumab and lapatinib.ERBB2
mutations occurred in 510 patients (2.85%). The tumor types with the highest
incidence of ERBB2 mutations were the following: bladder (16.6%), small bowel
(8.6%), ampullar (6.5%), skin non-melanoma (6.1%), and cervical cancer (5.5%).
49.4% (n = 282) were known as activating mutations. ERBB2 mutation was not
mutually exclusive of ERBB2 amplification which occurred in up to 10% of cases.
PI3KCA activating mutations were associated with ERBB2 mutations in 12.4% of
cases mainly in breast and lung cancer. Four patients (endometrial, colorectal,
cholangiocarcinoma, and adenosarcoma of the uterus) were treated with a
combination of trastuzumab and lapatinib. All of them experienced tumor shrinkage
resulting in stable disease in three cases and partial response in one case. One
patient developed secondary resistance. Sequencing of the progressing metastasis
allowed the identification of the ERBB2 L869R mutation previously associated with
resistance to lapatinib in vitro.These results support further clinical
investigation aiming to demonstrate that ERBB2-mutational driven therapy can
improve patient care irrespective of histology.
PMID- 29941009
TI - Status of nutrients important in brain function in phenylketonuria: a systematic
review and meta-analysis.
AB - BACKGROUND: Despite early and ongoing dietary management with a phe-restricted
diet, suboptimal neuropsychological function has been observed in PKU. The
restrictive nature of the PKU diet may expose patients to sub-optimal nutritional
intake and deficiencies which may impact normal brain function. A systematic
review of the published literature was carried out, where possible with meta
analysis, to compare the status of nutrients (Nutrients: DHA, EPA phospholipids,
selenium, vitamins B6, B12, E, C, A, D, folic acid, choline, uridine, calcium,
magnesium, zinc, iron, iodine and cholesterol) known to be important for brain
development and functioning between individuals with PKU and healthy controls.
RESULTS: Of 1534 publications identified, 65 studies met the entry criteria.
Significantly lower levels of DHA, EPA and cholesterol were found for PKU
patients compared to healthy controls. No significant differences in zinc,
vitamins B12, E and D, calcium, iron and magnesium were found between PKU
patients and controls. Because of considerable heterogeneity, the meta-analyses
findings for folate and selenium were not reported. Due to an insufficient number
of publications (< 4) no meta-analysis was undertaken for vitamins A, C and B6,
choline, uridine, iodine and phospholipids. CONCLUSIONS: The current data show
that PKU patients have lower availability of DHA, EPA and cholesterol. Compliance
with the phe-restricted diet including the micronutrient fortified protein
substitute (PS) is essential to ensure adequate micronutrient status. Given the
complexity of the diet, patients' micronutrient and fatty acid status should be
continuously monitored, with a particular focus on patients who are non-compliant
or poorly compliant with their PS. Given their key role in brain function,
assessment of the status of nutrients where limited data was found (e.g. choline,
iodine) should be undertaken. Standardised reporting of studies in PKU would
strengthen the output of meta-analysis and so better inform best practice for
this rare condition.
PMID- 29941011
TI - Criteria for evaluating transferability of health interventions: a systematic
review and thematic synthesis.
AB - BACKGROUND: Improving the public's health in different countries requires the
consideration of diverse health care systems and settings. For evidence-based
public health, decision-makers need to consider the transferability of effective
health interventions from a primary context to their specific target context. The
aim of this systematic review was to develop a model for the assessment of
transferability of health interventions through identification and
systematization of influencing criteria, including facilitators and barriers.
METHODS: A systematic literature search was performed in the databases PubMed,
Embase, CINAHL, and PsycINFO. Articles were eligible if they were published in
English or German and provided a description of transferability criteria.
Included articles were ranked based on their thematic relevance and
methodological support of transferability criteria. Using a qualitative approach,
a thematic synthesis was conducted. RESULTS: Thirty-seven articles were included
in the review. The thematic synthesis revealed 44 criteria, covered by 4
overarching themes, which influence transferability of health interventions: The
population (P), the intervention (I), and the environment (E) represent 30
conditional transferability criteria, and the transfer of the intervention (T)
represents 14 process criteria for transferring the intervention to the target
context. Transferability (-T) depends on the dynamic interaction of conditional
criteria in the primary and target context as well as on the process of transfer.
The description of facilitators and barriers deepens the understanding of the
criteria. The synthesis resulted in two related models: the conceptual PIET-T
model explains the underlying mechanism of transferability of health
interventions and the PIET-T process model provides practical guidance for a
transferability assessment. CONCLUSIONS: Transferability of health interventions
is a complex concept, which needs systematic consideration of the primary and
target context. It should be anticipated before and evaluated after an
intervention is implemented in the target context. Therefore, decision-makers
need systematic and practically relevant knowledge on transferability. The
synthesized PIET-T conceptual and process models with systematized criteria,
facilitators, and barriers are intended as a theoretical basis to determine
transferability of health interventions. Further research is needed to develop a
practical tool for the PIET-T models and to evaluate the tool's usefulness for
decision-making processes and intervention transfer.
PMID- 29941012
TI - Jugular vs femoral vein for central venous catheterization in pediatric cardiac
surgery (PRECiSE): study protocol for a randomized controlled trial.
AB - BACKGROUND: Placement of central venous catheters (CVCs) is essential and routine
practice in the management of children with congenital heart disease. The purpose
of the present protocol is to evaluate the risk for infectious complications in
terms of catheter colonization, catheter line-associated bloodstream infections,
and catheter-related bloodstream infections (CRBSIs), and the mechanical
complications from different central venous access sites in infants and newborns
undergoing cardiac surgery. METHODS: One hundred sixty patients under 1 year of
age and scheduled for cardiac surgery will be included in this randomized
controlled trial (RCT); patients will be randomly allocated to the jugular or
femoral vein arms. CVC insertion will be performed by one of three selected
expert operators. DISCUSSION: The choice of the insertion site for central venous
catheterization can influence the incidence and type of infectious complications
in adults but this is not unanimously evidenced in the pediatric setting. The
experimental hypothesis of this RCT is that the jugular insertion site is less
likely to induce catheter colonization and CRBSI than the femoral site. TRIAL
REGISTRATION: ClinicalTrials.gov Identifier: NCT03282292 . Registered on 12
September 2017.
PMID- 29941013
TI - Molecular identification of Bartonella bacilliformis in ticks collected from two
species of wild mammals in Madre de Dios: Peru.
AB - OBJECTIVE: To study the presence of Bartonella bacilliformis in ticks collected
from two wild mammals in Madre de Dios, Peru. RESULTS: A total of 110 ticks were
collected. Among the 43 Amblyomma spp. extracted from the 3 Tapirus terrestris
only 3 were positive for B. bacilliformis. In addition, 12 out of the 67
Rhipicephalus (Boophilus) microplus obtained from the 3 Pecari tajacu were
positive for B. bacilliformis. For the first time B. bacilliformis have been
detected in arthropods other than Lutzomyia spp. Further studies are required to
elucidate the possible role of ticks in the spread of South American
Bartonellosis.
PMID- 29941014
TI - Inflammation down-regulates CYP3A4-catalysed drug metabolism in hemodialysis
patients.
AB - BACKGROUND: Recent studies indicate that inflammation may also affect CYP3A4
activity. Associations of CYP3A4-mediated metabolism of quinine, with
inflammatory biomarkers were investigated in patients undergoing maintenance
hemodialysis (HD). METHODS: A single dose of 100 mg quinine was given to 44 HD
patients and the plasma concentration of quinine and its metabolite 3-OH-quinine
were measured 12 h after drug intake. The ratios of quinine/3-OH-quinine and
4beta-OH-cholesterol/cholesterol were used as markers of CYP3A4 activity.
Inflammatory biomarkers, high-sensitive CRP (hsCRP), pentraxin 3 (PTX3) and
orosomucoid were followed during 4 weeks prior to quinine administration.
RESULTS: The quinine/3-OH-quinine ratio correlated with median concentrations of
hsCRP (Rho = 0.48; p = 0.001) and orosomucoid (Rho = 0.44; p = 0.003), and also
with interleukin-6 at 12 h after drug intake (Rho = 0.43; P = 0.004) but not
PTX3. In multivariate regression analysis, the correlation between CYP3A4
activity and median hsCRP remained borderline significant (p = 0.05). 4beta-OH
cholesterol/cholesterol ratio correlated with quinine/3-OH-quinine (p = 0.008),
but not with any of the inflammation markers. CONCLUSIONS: The association
between CYP3A4 activity and inflammatory biomarkers suggest that the activity of
CYP3A4 is reduced by inflammation in HD patients. Further studies are needed to
confirm this finding and to assess to what extent magnitude and duration of
inflammation as well as the microbiota affect drug metabolism.
PMID- 29941015
TI - Human immunodeficiency virus associated pulmonary conditions leading to hospital
admission and the pulmonary rehabilitation services received by patients at two
central hospitals in Harare.
AB - OBJECTIVE: Use of highly active antiretroviral therapy has led to marked
reductions in the incidence of HIV-associated opportunistic infections but has
had comparatively less impact on the incidence of some pulmonary diseases. This
study was done to determine the pulmonary conditions leading to hospital
admissions in people living with HIV/AIDS at two central hospitals in Zimbabwe
and the pulmonary rehabilitation intervention received. RESULTS: A total of 92
participants were recruited of which 60 (65.2%) were females. The mean age of the
participants was 41.3 years (SD = 9.1). The most common pulmonary condition
leading to hospital admission was tuberculosis in 53 (57.6%). About 52 (56.6%) of
the participants suffered from pulmonary complications in the last 6 months, 48
(92.3%) were admitted and 26 (50.0%) of the participants received physiotherapy
treatment during their admission. None of the participants indicated that they
once attended an outpatient pulmonary rehabilitation clinic. Respiratory
complication is one of the leading causes of morbidity associated with HIV but no
pulmonary rehabilitation services are being offered to these patients. There is
need for introduction of pulmonary rehabilitation programs for people living with
HIV/AIDS in the current setting.
PMID- 29941016
TI - Whole body transcriptomes and new insights into the biology of the tick Ixodes
ricinus.
AB - BACKGROUND: Ixodes ricinus is the most important vector of tick-borne diseases in
Europe. A better knowledge of its genome and transcriptome is important for
developing control strategies. Previous transcriptomic studies of I. ricinus have
focused on gene expression during the blood meal in specific tissues. To obtain a
broader picture of changes in gene expression during the blood meal, our study
analysed the transcriptome at the level of the whole body for both nymphal and
adult ticks. Ixodes ricinus ticks from a highly inbred colony at the University
of Neuchatel were used. We also analysed previously published RNAseq studies to
compare the genetic variation between three wild strains and three laboratory
strains, including the strain from Neuchatel. RESULTS: RNA was extracted from
whole tick bodies and the cDNA was sequenced, producing 162,872,698 paired-end
reads. Our reference transcriptome contained 179,316 contigs, of which 31% were
annotated using Trinotate. Gene expression was compared between ticks that
differed by feeding status (unfed vs partially fed). We found that blood-feeding
in nymphs and female adult ticks increased the expression of cuticle-associated
genes. Using a set of 3866 single nucleotide polymorphisms to calculate the
heterozygosity, we found that the wild tick populations of I. ricinus had much
higher levels of heterozygosity than the three laboratory populations.
CONCLUSION: Using high throughput strand-oriented sequencing for whole ticks in
different stages and feeding conditions, we obtained a de novo assembly that
significantly increased the genomic resources available for I. ricinus. Our study
illustrates the importance of analysing the transcriptome at the level of the
whole body to gain additional insights into how gene expression changes over the
life-cycle of an organism. Our comparison of several RNAseq datasets shows the
power of transcriptomic data to accurately characterize genetic polymorphism and
for comparing different populations or sources of sequencing material.
PMID- 29941017
TI - A Mycobacterium avium subsp. paratuberculosis relA deletion mutant and a 35 kDa
major membrane protein elicit development of cytotoxic T lymphocytes with ability
to kill intracellular bacteria.
AB - Efforts to develop live attenuated vaccines against Mycobacterium avium
subspecies paratuberculosis (Map), using indirect methods to screen Map deletion
mutants for potential efficacy, have not been successful. A reduction in the
capacity to survive in macrophages has not predicted the ability of mutants to
survive in vivo. Previous studies for screening of three deletion mutants in
cattle and goats revealed one mutant, with a deletion in relA (DeltaMap/relA),
could not establish a persistent infection. Further studies, using antigen
presenting cells (APC), blood dendritic cells and monocyte derived DC, pulsed
with DeltaMap/relA or a 35 kDa Map membrane protein (MMP) revealed a component of
the response to DeltaMap/relA was directed towards MMP. As reported herein, we
developed a bacterium viability assay and cell culture assays for analysis and
evaluation of cytotoxic T cells generated against DeltaMap/relA or MMP. Analysis
of the effector activity of responding cells revealed the reason DeltaMap/relA
could not establish a persistent infection was that vaccination elicited
development of cytotoxic CD8 T cells (CTL) with the capacity to kill
intracellular bacteria. We demonstrated the same CTL response could be elicited
with two rounds of antigenic stimulation of APC pulsed with DeltaMap/relA or MMP
ex vivo. Cytotoxicity was mediated through the perforin granzyme B pathway.
Finally, cognate recognition of peptides presented in context of MHC I and II
molecules to CD4 and CD8 T cells is required for development of CTL.
PMID- 29941018
TI - CT during celiac artery angiography for localization of clinically suspected
small insulinomas.
AB - BACKGROUND: To identify location and number of insulinomas before operation is
very important for improving the cure rate. The objective of the study was to
assess performance of CT during celiac artery angiography for preoperative
localization of clinically suspected small insulinomas (< 2 cm in diameter).
METHODS: From January 2013 to November 2016, 42 patients with hypoglycemic
symptoms underwent celiac artery angiography, superior mesenteric artery
angiography and CT during celiac artery angiography by a combined CT/digital
subtraction angiography system, MIYABI Angio CT plus an Artiszeeceiling (SIEMENS,
Germany). Patient group consisted of 13 males and 29 females, age 17-69 years
(average, 45.4 +/- 13.5 y). After diagnosis, all 42 patients were operated.
Obtained images were retrospectively analyzed and compared with findings from
post-operation pathology. RESULTS: All interventional radiology procedures were
performed successfully with no complications. Sensitivity of angiography alone
for insulinoma was 76.1% (32/42), at combined CT/digital subtraction angiography,
4 more nodules were found (sensitivity, 85.7%, 36/42), while 6 false-negatives
were observed (all false negative lesions were less than 2 cm). A total of 64 ml
to 80 ml contrast media was used per patient. CONCLUSION: CT during celiac artery
angiography is a sensitive diagnostic procedure for localizing insulinomas.
Combined with angiography, it can prioritize the pancreatic region for
exploration and guide a pancreatic resection. TRIAL REGISTRATION: Ethical
approval was obtained from the Hospital Research Ethics Committee. Informed
consent was obtained from all patients included in the study. Duan Feng, Bai Yan
hua and Cui Li are co-first authors.
PMID- 29941019
TI - Efficacy and mechanism of sub-sensory sacral (optimised) neuromodulation in
adults with faecal incontinence: study protocol for a randomised controlled
trial.
AB - BACKGROUND: Faecal incontinence (FI) is a substantial health problem with a
prevalence of approximately 8% in community-dwelling populations. Sacral
neuromodulation (SNM) is considered the first-line surgical treatment option in
adults with FI in whom conservative therapies have failed. The clinical efficacy
of SNM has never been rigorously determined in a trial setting and the underlying
mechanism of action remains unclear. METHODS/DESIGN: The design encompasses a
multicentre, randomised, double-blind crossover trial and cohort follow-up study.
Ninety participants will be randomised to one of two groups (SNM/SHAM or
SHAM/SNM) in an allocation ratio of 1:1. The main inclusion criteria will be
adults aged 18-75 years meeting Rome III and ICI definitions of FI, who have
failed non-surgical treatments to the UK standard, who have a minimum of eight FI
episodes in a 4-week screening period, and who are clinically suitable for SNM.
The primary objective is to estimate the clinical efficacy of sub-sensory SNM vs.
SHAM at 32 weeks based on the primary outcome of frequency of FI episodes using a
4-week paper diary, using mixed Poisson regression analysis on the intention-to
treat principle. The study is powered (0.9) to detect a 30% reduction in
frequency of FI episodes between sub-sensory SNM and SHAM stimulation over a 32
week crossover period. Secondary objectives include: measurement of established
and new clinical outcomes after 1 year of therapy using new (2017 published)
optimised therapy (with standardised SNM-lead placement); validation of new
electronic outcome measures (events) and a device to record them, and
identification of potential biological effects of SNM on underlying anorectal
afferent neuronal pathophysiology (hypothesis: SNM leads to increased frequency
of perceived transient anal sphincter relaxations; improved conscious sensation
of defaecatory urge and cortical/subcortical changes in afferent responses to
anorectal electrical stimulation (main techniques: high-resolution anorectal
manometry and magnetoencephalography). DISCUSSION: This trial will determine
clinical effect size for sub-sensory chronic electrical stimulation of the sacral
innervation. It will provide experimental evidence of modifiable afferent
neurophysiology that may aid future patient selection as well as a basic
understanding of the pathophysiology of FI. TRIAL REGISTRATION: International
Standard Randomised Controlled Trial Number: ISRCTN98760715 . Registered on 15
September 2017.
PMID- 29941020
TI - Tailoring and evaluating an intervention to improve shared decision-making among
seniors with dementia, their caregivers, and healthcare providers: study protocol
for a randomized controlled trial.
AB - BACKGROUND: The increasing prevalence of Alzheimer's disease and other forms of
dementia raises new challenges to ensure that healthcare decisions are informed
by research evidence and reflect what is important for seniors and their
caregivers. Therefore, we aim to evaluate a tailored intervention to help
healthcare providers empower seniors and their caregivers in making health
related decisions. METHODS: In two phases, we will: (1) design and tailor the
intervention; and (2) implement and evaluate it. We will use theory and user
centered design to tailor an intervention comprising a distance professional
training program on shared decision-making and five shared decision-making tools
dealing with difficult decisions often faced by seniors with dementia and their
caregivers. Each tool will be designed in two versions, one for clinicians and
one for patients. We will recruit 49 clinicians and 27 senior/caregiver to
participate in three cycles of design-evaluation-feedback of each intervention
components. Besides think-aloud and interview approaches, users will also
complete questionnaires based on the Theory of Planned Behavior to identify the
factors most likely to influence their adoption of shared decision-making after
exposure to the intervention. We will then modify the intervention by
adding/enhancing behavior-change techniques targeting these factors. We will
evaluate the effectiveness of this tailored intervention before/after
implementation, in a two-armed, clustered randomized trial. We will enroll a
convenience sample of six primary care clinics (unit of randomization) in the
province of Quebec and recruit the clinicians who practice there (mostly family
physicians, nurses, and social workers). These clinics will then be randomized to
immediate exposure to the intervention or delayed exposure. Overall, we will
recruit 180 seniors with dementia, their caregivers, and their healthcare
providers. We will evaluate the impact of the intervention on patient involvement
in the decision-making process, decisional comfort, patient and caregiver
personal empowerment in relation to their own healthcare, patient quality of
life, caregiver burden, and decisional regret. DISCUSSION: The intervention will
empower patients and their caregivers in their healthcare, by fostering their
participation as partners during the decision-making process and by ensuring they
make informed decisions congruent with their values and priorities. TRIAL
REGISTRATION: ClinicalTrials.org, NCT02956694 . Registered on 31 October 2016.
PMID- 29941021
TI - Investigation of the efficacy of fluralaner spot-on (Bravecto(r)) against
infestations of Ixodes holocyclus on cats.
AB - BACKGROUND: Infestation of cats with the Australian paralysis tick, Ixodes
holocyclus continues to be a threat because of the paralysis that can result from
attachment of just a single tick. The outcome can be fatal, particularly if tick
removal and treatment is not initiated soon after the onset of paralysis.
However, there are no published studies to guide veterinarians and owners on
preventive measures. A study was therefore initiated to determine the efficacy of
a systemically-acting, spot-on formulation of fluralaner (Bravecto(r)) for cats
against existing I. holocyclus infestations, and to investigate the duration of
protection following a single administration. METHODS: Healthy domestic cats,
short or long-hair, immunized against holocyclotoxin, were randomly allocated to
two groups of 10 cats per group, to receive either a single topically applied
fluralaner treatment or no treatment. Fluralaner treatments were administered on
Day 0 at a dose rate of 40 mg/kg. All cats were infested with 10 adult unfed
female I. holocyclus on Day -1 and on Days 14, 28, 42, 56, 70 and 84. Ticks were
assessed at 24 and 48 h after fluralaner treatment and 24, 48 and 72 hours after
each subsequent re-infestation. Ticks were counted but not removed at the 24- and
48-h post-challenge assessments and were removed following the 72-h counts.
RESULTS: The efficacy of fluralaner spot-on against an existing I. holocyclus
infestation was 100% at 48 h post treatment. Following re-infestations, efficacy
remained at 100% at the 72-h assessments for all challenges from Day 14 to Day
84. Differences between mean live tick counts on treated versus control cats were
significant at all time points from the first post-treatment assessment (t-test:
t(18) = 23.162; P < 0.0001) through the final challenge on Day 84 (t-test: t(18)
= 21.153; P < 0.0001). No treatment-related adverse events were observed and
there were no abnormal observations at the product application sites.
CONCLUSIONS: A single treatment of fluralaner spot-on was well tolerated and
provided 100% efficacy against I. holocyclus ticks for at least 84 days.
Fluralaner spot-on can be a valuable tool to prevent tick infestation in cats,
and to control the risk of I. holocyclus-induced paralysis.
PMID- 29941022
TI - Early gestational mesenchymal stem cell secretome attenuates experimental
bronchopulmonary dysplasia in part via exosome-associated factor TSG-6.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) are promising tools for the treatment
of human lung disease and other pathologies relevant to newborn medicine. Recent
studies have established MSC exosomes (EXO), as one of the main therapeutic
vectors of MSCs in mouse models of multifactorial chronic lung disease of preterm
infants, bronchopulmonary dysplasia (BPD). However, the mechanisms underlying MSC
EXO therapeutic action are not completely understood. Using a neonatal mouse
model of human BPD, we evaluated the therapeutic efficiency of early gestational
age (GA) human umbilical cord (hUC)-derived MSC EXO fraction and its exosomal
factor, tumor necrosis factor alpha-stimulated gene-6 (TSG-6). METHODS:
Conditioned media (CM) and EXO fractions were isolated from 25 and 30 weeks GA
hUC-MSC cultures grown in serum-free media (SFM) for 24 h. Newborn mice were
exposed to hyperoxia (> 95% oxygen) and were given intraperitoneal injections of
MSC-CM or MSC-CM EXO fractions at postnatal (PN) day 2 and PN4. They were then
returned to room air until PN14 (in a mouse model of severe BPD). The treatment
regime was followed with (rh)TSG-6, TSG-6-neutralizing antibody (NAb), TSG-6
(si)RNA-transfected MSC-CM EXO and their appropriate controls. Echocardiography
was done at PN14 followed by harvesting of lung, heart and brain for assessment
of pathology parameters. RESULTS: Systemic administration of CM or EXO in the
neonatal BPD mouse model resulted in robust improvement in lung, cardiac and
brain pathology. Hyperoxia-exposed BPD mice exhibited pulmonary inflammation
accompanied by alveolar-capillary leakage, increased chord length, and alveolar
simplification, which was ameliorated by MSC CM/EXO treatment. Pulmonary
hypertension and right ventricular hypertrophy was also corrected. Cell death in
brain was decreased and the hypomyelination reversed. Importantly, we detected
TSG-6, an immunomodulatory glycoprotein, in EXO. Administration of TSG-6
attenuated BPD and its associated pathologies, in lung, heart and brain.
Knockdown of TSG-6 by NAb or by siRNA in EXO abrogated the therapeutic effects of
EXO, suggesting TSG-6 as an important therapeutic molecule. CONCLUSIONS: Preterm
hUC-derived MSC-CM EXO alleviates hyperoxia-induced BPD and its associated
pathologies, in part, via exosomal factor TSG-6. The work indicates early
systemic intervention with TSG-6 as a robust option for cell-free therapy,
particularly for treating BPD.
PMID- 29941023
TI - Maternal depression does not affect complementary feeding indicators or stunting
status of young children (6-23 months) in Northern Ghana.
AB - OBJECTIVE: Maternal depression may affect child feeding practice which is an
important determinant of child nutritional status. The objective of this study
was to explore the association between maternal depression and WHO complementary
feeding indicators [minimum dietary diversity (MDD), minimum meal frequency (MMF)
and minimum acceptable diet (MAD)] or stunting status of children (6-23 months)
in Tamale Metropolis, Ghana. A community-based cross-sectional study was carried
out involving 200 mother-child pairs randomly sampled from three communities in
Tamale Metropolis, Ghana. RESULTS: The prevalence of MDD, MMF, and MAD were 56.5,
65.0, and 44.0% respectively and 41.0% of the children sampled were stunted. A
third of the mothers (33.5%) screened positive for depression. Maternal
depression did not influence significantly MDD (p = 0.245), MMF (p = 0.442), and
MAD (p = 0.885) or children's risk of stunting (p = 0.872). In conclusion
maternal depression and child stunting are prevalent in Northern Ghana but there
is a lack of evidence of an association between maternal depression and child
feeding practices or nutritional status in this study population. Further
research is needed to assess the effect of maternal depression on feeding
practices and growth of young children.
PMID- 29941025
TI - Suicidal jumper's fracture - sacral fractures and spinopelvic instability: a case
series.
AB - BACKGROUND: Sacral fractures with spinopelvic dissociation are rare, and hard to
diagnose and treat. Fractures with a H- or U-shaped line are severely unstable,
due to a dissociation of the spine and of the upper body of the sacrum from the
pelvis. They are commonly due to high-energy trauma events, with severe
neurological injuries in 80% of cases. CASES PRESENTATION: Five polytraumatized
Caucasian patients, three women and two men (mean age: 34 years old) with
spinopelvic dissociation were selected. All patients underwent level I-II
examinations with radiographs and computed tomography total-body scans; all
patients needed damage-control procedures. Sacral fractures were classified
according to Denis and Roy-Camille classifications, and neurologic injuries of
cauda equina according to Gibbons classification. Patients' outcome was analyzed
with the Majeed score. Definitive surgical treatment was appropriate for two
patients (lumbar-pelvic fixation or transverse bar). Clinical and radiographic
outcomes were analyzed periodically. Four patients survived, all of them suffered
severe neurologic deficits. One case of osteomyelitis was treated with the
removal of the fixation implants 23 months after the accident. CONCLUSIONS:
Diagnosis of spinopelvic dissociation is frequently overlooked due to the severe
associated injuries affecting these patients. In cases of a fall from high
height, this lesion should be investigated with a lateral sacral radiographic
view and computed tomography scan of the pelvis. If untreated, it can lead to
severe and progressive neurologic deficit with muskuloskeletal deformities and
persistent pain. Early decompression treatment is controversial, but an early
lumbopelvic fixation is recommended. A correct diagnosis and early treatment can
reduce morbidity and strongly improve the outcome of these patients.
PMID- 29941024
TI - Effects of an exercise program on hepatic metabolism, hepatic fat, and
cardiovascular health in overweight/obese adolescents from Bogota, Colombia (the
HEPAFIT study): study protocol for a randomized controlled trial.
AB - BACKGROUND: A considerable proportion of contemporary youth have a high risk of
obesity-related disorders such as cardiovascular disease, metabolic syndrome, or
non-alcoholic fatty liver disease (NAFLD). Although there is consistent evidence
for the positive effects of physical activity on several health aspects, most
adolescents in Colombia are sedentary. It is, therefore, important to implement
strategies that generate changes in lifestyle. The HEPAFIT study aims to examine
whether a 6-month exercise program has benefits for hepatic fat content and
cardiovascular health outcomes among overweight/obese adolescents from Bogota,
Colombia. METHODS/DESIGN: Altogether, 100 hundred overweight/obese, sedentary
adolescents (aged 11-17 years) attending two public schools in Bogota, Colombia,
will be included in a parallel-group randomized controlled trial. Adolescents
will be randomly assigned to an intervention group following one of four
curricula: (1) the standard physical education curriculum (60 min per week of
physical activity, n = 25) at low-to-moderate intensity; (2) a high-intensity
physical education curriculum (HIPE, n = 25), consisting of endurance and
resistance games and non-competitive activities, such as running, gymkhanas,
lifting, pushing, wrestling, or hauling, for 60-min sessions, three times per
week, with an energy expenditure goal of 300 to 500 kcal/session at 75-85%
maximum heart rate (HRmax); (3) a low-to-moderate intensity physical education
curriculum (LIPE, n = 25) consisting of endurance and resistance games and non
competitive activities (e.g., chasing, sprinting, dribbling, or hopping) for 60
min sessions, three times per week with an energy expenditure goal of 300
kcal/session at 55-75% HRmax; and (4) a combined HIPE and LIPE curriculum (n =
25). The HIPE, LIPE, and combined interventions were performed in addition to the
standard physical education curriculum. The primary outcome for effectiveness is
liver fat content, as measured by the controlled attenuation parameter 1 week
after the end of the intervention program. DISCUSSION: The translational focus
may be suitable for collecting new information in a school setting on the
possible effects of physical activity interventions to reduce liver fat content
and to improve metabolic profiles and the cardiometabolic health of
overweight/obese adolescents. This may lead to the more efficient use of school
physical education resources. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02753231
. Registered on 21 April 2016.
PMID- 29941026
TI - Screening of a library of traditional Chinese medicines to identify anti-malarial
compounds and extracts.
AB - BACKGROUND: Malaria is a major infectious disease in the world. In 2015,
approximately 212 million people were infected and 429,000 people were killed by
this disease. Plasmodium falciparum, which causes falciparum malaria, is becoming
resistant to artemisinin (ART) in Southeast Asia; therefore, new anti-malarial
drugs are urgently needed. Some excellent anti-malarial drugs, such as quinine or
ART, were originally obtained from natural plants. Hence, the authors screened a
natural product library comprising traditional Chinese medicines (TCMs) to
identify compounds/extracts with anti-malarial effects. METHODS: The authors
performed three assays: a malaria growth inhibition assay (GIA), a cytotoxicity
assay, and a malaria stage-specific GIA. The malaria GIA revealed the anti
malarial ability and half-maximal inhibitory concentrations (IC50) of the natural
products, whereas the malaria stage-specific GIA revealed the point in the
malaria life cycle where the products exerted their anti-malarial effects. The
toxicity of the products to the host cells was evaluated with the cytotoxicity
assay. RESULTS: Four natural compounds (berberine chloride, coptisine chloride,
palmatine chloride, and dehydrocorydaline nitrate) showed strong anti-malarial
effects (IC50 < 50 nM), and low cytotoxicity (cell viability > 90%) using P.
falciparum 3D7 strain. Two natural extracts (Phellodendri cortex and Coptidis
rhizoma) also showed strong antiplasmodial effects (IC50 < 1 ug/ml), and low
cytotoxicity (cell viability > 80%). These natural products also demonstrated
anti-malarial capability during the trophozoite and schizont stages of the
malaria life cycle. CONCLUSIONS: The authors identified four compounds (berberine
chloride, coptisine chloride, palmatine chloride, and dehydrocorydaline nitrate)
and two extracts (Phellodendri cortex and Coptidis rhizoma) with anti-malarial
activity, neither of which had previously been described. The IC50 values of the
compounds were comparable to that of chloroquine and better than that of
pyrimethamine. These compounds and extracts derived from TCMs thus show promise
as potential future anti-malarial drugs.
PMID- 29941027
TI - Intrathoracic pressure regulation therapy applied to ventilated patients for
treatment of compromised cerebral perfusion from brain injury.
AB - BACKGROUND: Reducing intrathoracic pressure in the setting of compromised
cerebral perfusion due to acute brain injury has been associated with reduced
intracranial pressure and enhanced cerebral perfusion pressure and blood flow in
animals. Noninvasive active intrathoracic pressure regulation lowers
intrathoracic pressure, increases preload, reduces the volume of venous blood and
cerebral spinal fluid in the skull, and enhances cerebral blood flow. We examined
the feasibility of active intrathoracic pressure regulation therapy in patients
with brain injury. We hypothesized that active intrathoracic pressure regulation
therapy would be associated with lowered intracranial pressure and increased
cerebral perfusion pressure in these patients. METHODS: At three institutions,
active intrathoracic pressure regulation therapy (CirQlatorTM, ZOLL) was utilized
for 2 consecutive hours in five mechanically ventilated patients with brain
injury. A 30-minute interval was used to collect baseline data and determine
persistence of effects after device use. End-tidal carbon dioxide was controlled
by respiratory rate changes during device use. The intracranial pressure, mean
arterial pressure, and cerebral perfusion pressure were recorded at 5-minute
intervals throughout all three periods of the protocol. Results for each interval
are reported as mean and standard deviation. RESULTS: Intracranial pressure was
decreased in all five patients by an average of 21% during (15 +/- 4 mmHg)
compared to before active intrathoracic pressure regulation (19 +/- 4) (p =
0.005). This effect on intracranial pressure (15 +/- 6) was still present in four
of the five patients 30 minutes after therapy was discontinued (p = 0.89). As a
result, cerebral perfusion pressure was 16% higher during (81 +/- 10) compared to
before active intrathoracic pressure regulation (70 +/- 14) (p = 0.04) and this
effect remained present 30 minutes after therapy was discontinued. No adverse
events were reported. CONCLUSIONS: These data support the notion that active
intrathoracic pressure regulation, in this limited evaluation, can successfully
augment cerebral perfusion by lowering intracranial pressure and increasing mean
arterial pressure in patients with mild brain injury. The measured effects were
immediate on administration of the therapy and persisted to some degree after the
therapy was terminated.
PMID- 29941028
TI - Protocol, and practical challenges, for a randomised controlled trial comparing
the impact of high intensity interval training against standard care before major
abdominal surgery: study protocol for a randomised controlled trial.
AB - BACKGROUND: Risk factors, such as the number of pre-existing co-morbidities, the
extent of the underlying pathology and the magnitude of the required operation,
cannot be changed before surgery. It may, however, be possible to improve the
cardiopulmonary fitness of the patient with an individualised exercise program.
We are performing a randomised controlled trial (RCT) assessing the impact of
High Intensity Interval Training (HIIT) on preoperative cardiopulmonary fitness
and postoperative outcomes in patients undergoing major abdominal surgery.
METHODS: Consecutive eligible patients undergoing elective abdominal surgery are
being randomised to HIIT or standard care in a 1:1 ratio. Participants allocated
to HIIT will perform 14 exercise sessions on a stationary cycle ergometer, over a
period of 4-6 weeks before surgery. The sessions, which are individualised, aim
to start with ten repeated 1-min blocks of intense exercise with a target of
reaching a heart rate exceeding 90% of the age predicted maximum, followed by 1
min of lower intensity cycling. As endurance improves, the duration of exercise
is increased to achieve five 2-min intervals of high intensity exercise followed
by 2 min of lower intensity cycling. Each training session lasts approximately 30
min. The primary endpoint, change in peak oxygen consumption (Peak VO2) measured
during cardiopulmonary exercise testing, is assessed at baseline and before
surgery. Secondary endpoints include postoperative complications, length of
hospital stay and three clinically validated scores: the surgical recovery scale;
the postoperative morbidity survey; and the SF-36 quality of life score. The
standard deviation for changes in Peak VO2 will be assessed after the first 30
patients and will be used to calculate the required sample size. DISCUSSION: We
want to assess if 14 sessions of HIIT is sufficient to improve Peak VO2 by 2
mL/kg/min in patients undergoing major abdominal surgery and to explore the best
clinical endpoint for a subsequent RCT designed to assess if improving Peak VO2
will translate into improving clinical outcomes after surgery. TRIAL
REGISTRATION: Australian New Zealand Clinical Trials Registry,
ACTRN12617000587303 . Registered on 26 April 2017.
PMID- 29941029
TI - Co-culturing nucleus pulposus mesenchymal stem cells with notochordal cell-rich
nucleus pulposus explants attenuates tumor necrosis factor-alpha-induced
senescence.
AB - BACKGROUND: Cell therapy for the treatment of intervertebral disc degeneration
(IDD) faces serious barriers since tissue-specific adult cells such as nucleus
pulposus cells (NPCs) have limited proliferative ability and poor regenerative
potential; in addition, it is difficult for exogenous adult stem cells to survive
the harsh environment of the degenerated intervertebral disc. Endogenous repair
by nucleus pulposus mesenchymal stem cells (NPMSCs) has recently shown promising
regenerative potential for the treatment of IDD. Notochordal cells (NCs) and NC
conditioned medium (NCCM) have been proven to possess regenerative ability for
the treatment of IDD, but this approach is limited by the isolation and passaging
of NCs. Our previous study demonstrated that modified notochordal cell-rich
nucleus pulposus (NC-rich NP) has potential for the repair of IDD. However,
whether this can protect NPMSCs during IDD has not been evaluated. METHODS: In
the current study, tumor necrosis factor (TNF)-alpha was used to mimic the
inflammatory environment of IDD. Human NPMSCs were cocultured with NC-rich NP
explants from healthy rabbit lumbar spine with or without TNF-alpha. Cell
proliferation and senescence were analyzed to investigate the effect of NC-rich
NP explants on TNF-alpha-treated NPMSCs. The expression of mRNA encoding proteins
related to matrix macromolecules (such as aggrecan, Sox-9, collagen Ialpha, and
collagen IIalpha), markers related to the nucleus pulposus cell phenotype
(including CA12, FOXF1, PAX1, and HIF-1alpha), and senescence markers (such as
p16, p21, and p53), senescence-associated proinflammatory cytokines (IL-6), and
extracellular proteases (MMP-13, ADAMTS-5) was assessed. The protein expression
of CA12 and collagen II was also evaluated. RESULTS: After a 7-day treatment, the
NC-rich NP explant was found to enhance cell proliferation, decrease cellular
senescence, promote glycosaminoglycan (GAG), collagen II, and CA12 production,
upregulate the expression of extracellular matrix (ECM)-related genes (collagen
I, collagen II, SOX9, and ACAN), and enhance the expression of nucleus pulposus
cell (NPC) markers (HIF-1alpha, FOXF1, PAX1, and CA12). CONCLUSION: Modified NC
rich NP explants can attenuate TNF-alpha-induced degeneration and senescence of
NPMSCs in vitro. Our findings provide new insights into the therapeutic potential
of NC-rich NP for the treatment of IDD.
PMID- 29941030
TI - Participation in a trial in the emergency situation: a qualitative study of
patient experience in the UK WOLLF trial.
AB - BACKGROUND: Patients can struggle to make sense of trials in emergency
situations. This study examines patient experience of participating in the United
Kingdom, Wound management of Open Lower Limb Fractures (UK WOLLF) study, a trial
of standard wound management versus Negative Pressure Wound Therapy (NPWT).
METHODS: The aim of the study was to understand the patient's lived experience of
taking part in a trial of wound dressings. Interviews drawing on Phenomenology
were undertaken with a purposive sample of 20 patients, on average 12 days into
their hospital stay from July 2012-July 2013. RESULTS: The participants were
vulnerable due to the emotional and physical impact of injury. They expressed
their trial experience through the theme of being compromised identified in
categories of being dependent, being trusting, being grateful and being without
experience. Participants felt dependent on and trusted the team to make the right
decisions for them and not cause them harm. Their hopes for future recovery were
also invested within the expertise of the team. Despite often not being well
enough to consent to the study prior to surgery, they wished to be involved as
much as possible. In agreeing to take part they expressed gratitude for their
care, wanted to be helpful to others and considered the trial interventions to be
a small component in relation to the enormity of their injury and broader
treatment. In making sense of the trial they felt they could not understand the
interventions without experience of them but if they received NPWT they developed
a strong technological preference for this intervention. CONCLUSIONS: Patients
prefer to be involved in studies within the limits of their capacity, despite not
being able to provide informed consent. A variety of sources of knowledge may
enable participants to feel that they have a better understanding of the
interventions. Professional staff need to be aware of the situated nature of
decision making where participants invest their hopes for recovery in the team.
TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN33756652 . Registered on
24 February 2012.
PMID- 29941031
TI - Twenty years of surveillance for Eastern equine encephalitis virus in mosquitoes
in New York State from 1993 to 2012.
AB - BACKGROUND: The year 1971 was the first time in New York State (NYS) that Eastern
equine encephalitis virus (EEEV) was identified in mosquitoes, in Culiseta
melanura and Culiseta morsitans. At that time, state and county health
departments began surveillance for EEEV in mosquitoes. METHODS: From 1993 to
2012, county health departments continued voluntary participation with the state
health department in mosquito and arbovirus surveillance. Adult female mosquitoes
were trapped, identified, and pooled. Mosquito pools were tested for EEEV by Vero
cell culture each of the twenty years. Beginning in 2000, mosquito extracts and
cell culture supernatant were tested by reverse transcriptase-polymerase chain
reaction (RT-PCR). RESULTS: During the years 1993 to 2012, EEEV was identified
in: Culiseta melanura, Culiseta morsitans, Coquillettidia perturbans, Aedes
canadensis (Ochlerotatus canadensis), Aedes vexans, Anopheles punctipennis,
Anopheles quadrimaculatus, Psorophora ferox, Culex salinarius, and Culex pipiens
restuans group. EEEV was detected in 427 adult mosquito pools of 107,156 pools
tested totaling 3.96 million mosquitoes. Detections of EEEV occurred in three
geographical regions of NYS: Sullivan County, Suffolk County, and the contiguous
counties of Madison, Oneida, Onondaga and Oswego. Detections of EEEV in
mosquitoes occurred every year from 2003 to 2012, inclusive. EEEV was not
detected in 1995, and 1998 to 2002, inclusive. CONCLUSIONS: This was the first
time in NYS that EEEV was detected in Cx. salinarius, Ps. ferox and An.
punctipennis. The detection of EEEV in mosquitoes every year for 10 years was the
longest time span since surveillance began in 1971. The calendar date of the
earliest annual appearance of EEEV in mosquitoes did not change during
surveillance spanning 42 years.
PMID- 29941032
TI - Intracranial meningeal melanocytoma diagnosed using an interdisciplinary
approach: a case report and review of the literature.
AB - BACKGROUND: Meningeal melanocytoma is a rare pigmented tumor arising from
leptomeningeal melanocytes. Patients with this tumor might initially consult a
dentist because a mass lesion in Meckel's cave could manifest as dental pain and
malocclusion, thereby mimicking temporomandibular disorder. The diagnostic
approach, especially using imaging modalities, would be challenging in such cases
unless an interdisciplinary approach is used. CASE PRESENTATION: Here, we report
a case of a 39-year-old Japanese man who had a history of pain and numbness on
the left side of his face and malocclusion for 3 months before the initial visit.
The diagnosis was primary intracranial meningeal melanocytoma arising from
Meckel's cave. CONCLUSIONS: The process by which the final diagnosis of meningeal
melanocytoma was reached highlights the importance of collaboration between the
medical and dental disciplines. This case also demonstrates that meningeal
melanocytoma has a specific signal pattern on magnetic resonance imaging,
including high signal intensity on T1-weighted images and low signal intensity on
T2-weighted images.
PMID- 29941033
TI - The research on 3D printing fingerboard and the initial application on cerebral
stroke patient's hand spasm.
AB - PURPOSE: To research the possibility of designing customized 3D printing
fingerboard to apply to the limb rehabilitation of cerebral stroke patients as
well as the prevention and treatment of finger spasm, through 3D printing
technology. METHODS: Taking 18 hospitalized cerebral stroke patients for example,
through scanning, molding and printing, to make and wear 3D printing fingerboard
for them, and then observe the compliance, main complaint, muscular tension of
affected hand and changes on range of motion after they wear the fingerboard for
3 weeks and 3 months. RESULTS: Have acquired completed data from 13 patients. The
time of them wearing the fingerboard every day varied from 1 to 8 h, and most of
them reflected that they felt comfortable and there was no feeling of worsened
pain or finger skin allergy. In addition, the patients' grip strength, hand
function and range of motion improved by varying degrees while their muscular
tensions declined by varying degrees. The tension and bending resistance of the
fingerboard all met the patients' treatment requirements. CONCLUSIONS: With the
advantages of being accurate and customized, 3D printing fingerboard can benefit
patients fixing and orthopedic treatment, and even prevent and treat cerebral
stroke patient's finger spasm. Trial registration The research topic has been
registered in Chinese Clinic Trial Registry. Registration time: January 15, 2016.
Registration topic: The Use of 3D Printing Technology in the Orthotic of
Extremity Rehabilitation of Stroke Patient. Registration Number: ChiCTR-INR
16007774.
PMID- 29941035
TI - Migratory polyarthritis as a paraneoplastic syndrome in a patient with diffuse
large B cell lymphoma: a case report.
AB - BACKGROUND: Diffuse large B cell lymphoma is the commonest histological subtype
of non-Hodgkin lymphoma and typically presents as a rapidly enlarging lymph node
mass and B symptoms. It is unusual for diffuse large B cell lymphoma to present
as carcinomatous polyarthritis which is a type of paraneoplastic arthritis. CASE
PRESENTATION: We present a case of a 45-year-old Asian man with diffuse large B
cell lymphoma presenting with generalized lymphadenopathy, transient macular
rash, and migratory polyarthritis involving both upper and lower limb small and
large joints. Treatment of the lymphoma but not the routine anti-inflammatory
agents resulted in complete resolution of the arthritis suggesting the
paraneoplastic nature. CONCLUSIONS: Poor response to routine therapy for
inflammatory arthritis should lead to early suspicion of paraneoplastic arthritis
which will prompt investigation for an underlying malignancy. Suspicion of
carcinomatous polyarthritis should be made in those with migratory polyarthritis
and should be thoroughly investigated to exclude underlying malignancy.
PMID- 29941034
TI - Income inequalities in multimorbidity prevalence in Ontario, Canada: a
decomposition analysis of linked survey and health administrative data.
AB - BACKGROUND: The burden of multimorbidity is a growing clinical and health system
problem that is known to be associated with socioeconomic status, yet our
understanding of the underlying determinants of inequalities in multimorbidity
and longitudinal trends in measured disparities remains limited. METHODS: We
included all adult respondents from four cycles of the Canadian Community Health
Survey (CCHS) (between 2005 to 2011/12), linked at the individual-level to health
administrative data in Ontario, Canada (pooled n = 113,627). Multimorbidity was
defined at each survey response as having >=2 (of 17) high impact chronic
conditions, based on claims data. Using a decomposition method of the Erreygers
corrected concentration index (CErreygers), we measured household income
inequality and the contribution of the key determinants of multimorbidity
(including socio-demographic, socio-economic, lifestyle and health system
factors) to these disparities. Differences over time are described. We tested for
statistically significant changes to measured inequality using the slope index
(SII) and relative index of inequality (RII) with a 2-way interaction on pooled
data. RESULTS: Multimorbidity prevalence in 2011/12 was 33.5% and the CErreygers
was - 0.085 (CI: -0.108 to - 0.062), indicating a greater prevalence among lower
income groups. In decomposition analyses, income itself accounted more than two
thirds (69%) of this inequality. Age (21.7%), marital status (15.2%) and physical
inactivity (10.9%) followed, and the contribution of these factors increased from
baseline (2005 CCHS survey) with the exception of age. Other lifestyle factors,
including heavy smoking and obesity, had minimal contribution to measured
inequality (1.8 and 0.4% respectively). Tests for trends (SII/RII) across pooled
survey data were not statistically significant (p = 0.443 and 0.405,
respectively), indicating no change in inequalities in multimorbidity prevalence
over the study period. CONCLUSIONS: A pro-rich income gap in multimorbidity has
persisted in Ontario from 2005 to 2011/12. These empirical findings suggest that
to advance equality in multimorbidity prevalence, policymakers should target
chronic disease prevention and control strategies focused on older adults, non
married persons and those that are physically inactive, in addition to addressing
income disparities directly.
PMID- 29941036
TI - Eph/Ephrin-mediated stimulation of human bone marrow mesenchymal stromal cells
correlates with changes in cell adherence and increased cell death.
AB - BACKGROUND: Mesenchymal stromal cells (MSC) are components of connective tissues
and, in vitro, cell entities characterized by cell adhesion and
immunophenotyping, although specific markers for their identification are
lacking. Currently, MSC derived from either human bone marrow (BM-MSC) or adipose
tissue (Ad-MSC) are considered the main sources of MSC for cell therapy. Eph
receptors and their ligands, Ephrins, are molecules involved in cell adhesion and
migration in several tissues and organs. In the current study, we analyze the
pattern of Eph/Ephrin expression in MSC and evaluate the effects of blockade and
stimulation of these receptor/ligand pairs on their biology. METHODS: Eph/Ephrin
expression was analyzed in both BM-MSC and Ad-MSC by qRT-PCR. Then, we supplied
BM-MSC cultures with either blocking or activating compounds to evaluate their
effects on MSC proliferation, survival, and cell cycle by FACS. Changes in
cytoskeleton and integrin alpha5beta1 expression were studied in stimulated BM
MSC by immunofluorescence microscopy and FACS, respectively. RESULTS: Higher
numbers of Eph/Ephrin transcripts occurred in BM-MSC than in Ad-MSC. In addition,
the blocking of Eph/Ephrin signaling correlated with decreased numbers of BM-MSC
due to increased proportions of apoptotic cells in the cultures but without
variations in the cycling cells. Unexpectedly, activation of Eph/Ephrin signaling
by clustered Eph/Ephrin fusion proteins also resulted in increased proportions of
apoptotic MSC. In this case, MSC underwent important morphological changes,
associated with altered cytoskeleton and integrin alpha5beta1 expression, which
did not occur under the blocking conditions. CONCLUSIONS: Taken together, these
results suggest that Eph/Ephrin activation affects cell survival through
alterations in cell attachment to culture plates, affecting the biology of BM
MSC.
PMID- 29941037
TI - Liuzijue Qigong vs traditional breathing training for patients with post-stroke
dysarthria complicated with abnormal respiratory control: study protocol of a
single center randomized controlled trial.
AB - BACKGROUND: Stroke-induced dysarthria is caused by muscle weakness, sacral or
muscular dystonia, and incoordination of the articulatory organ formed by organic
lesions caused by cerebral vascular obstruction or sudden bursting of blood
vessels in the brain, which may cause abnormal breathing patterns, pronunciation,
resonance, rhythm, and unclear articulation. The Six Character Formula, or
Liuzijue qigong (LQG), is an essential part of Chinese traditional exercises and
focuses on breathing-speech synchronization. The purpose of the present study was
to compare the effects of LQG with traditional breathing training (combined with
basic articulation training in both groups) in patients with post-stroke
dysarthria. METHODS/DESIGN: The proposed study will be a single-center randomized
controlled trial. A total of 100 patients, with a modified Frenchay Dysarthria
Assessment (FDA) dysarthria assessment score < 27 and with a FDA speech breathing
level >= b will be randomly divided into study (LQG, n = 50) and control
(conventional breathing training, n = 50) groups. Basic articulation training
will be conducted once a day, five times a week for 3 weeks. Data collection will
be conducted at baseline, 1 week, and 2 weeks post-treatment initiation and after
completion of the treatment (3 weeks). Comprehensive analyses will be conducted
to measure and compare any differences in speech breathing dysfunction levels,
comprehensive evaluation of dysarthria, maximum phonation time (MPT), maximal
counting ability, signal-noise (S/Z) ratio, and loudness scales between the study
and control groups. DISCUSSION: This trial will provide evidence about the
effectiveness of LQG for improvement of speech breathing function and speech
ability in patients with post-stroke dysarthria complicated with abnormal
breathing. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR
16010215. Registered 21 December 2016.
PMID- 29941038
TI - Model-based analysis of experimental data from interconnected, row-configured
huts elucidates multifaceted effects of a volatile chemical on Aedes aegypti
mosquitoes.
AB - BACKGROUND: Insecticides used against Aedes aegypti and other disease vectors can
elicit a multitude of dose-dependent effects on behavioral and bionomic traits.
Estimating the potential epidemiological impact of a product requires thorough
understanding of these effects and their interplay at different dosages. Volatile
spatial repellent (SR) products come with an additional layer of complexity due
to the potential for altered movement of affected mosquitoes and diffusion of
volatile particles of the product beyond the treated house. Here, we propose a
paired experimental design and statistical inference framework for estimating
these nuanced effects of volatile SRs. METHOD: We fitted a continuous-time Markov
chain model in a Bayesian framework to data on marked mosquitoes released in
interconnected experimental huts conducted in Iquitos, Peru. We estimated the
effects of two dosages of transfluthrin on Ae. aegypti behaviors associated with
human-vector contact: repellency, exiting and knockdown in the treated space and
in connected, adjacent huts. We validated the framework using simulated data.
RESULTS: The odds of a female Ae. aegypti being repelled, and thus prevented from
entering a treated hut (HT), increased at both dosages (low dosage: odds = 1.64,
95% highest density interval (HDI) = 1.30-2.09; high dosage: odds = 1.35, HDI =
1.04-1.67). The relative risk of exiting from the treated hut was reduced (low:
RR = 0.70, HDI = 0.62-1.09; high: RR = 0.70, HDI = 0.40-1.06), with this effect
carrying over to untreated spaces two huts away from the treated hut (H2) (low:
RR = 0.79, HDI = 0.59-1.01; high: RR = 0.66, HDI = 0.50-0.87). Knockdown rates
were increased in both treated and downstream huts, particularly under high
dosage (HT: RR = 8.37, HDI = 2.11-17.35; H1: RR = 1.39, HDI = 0.52-2.69; H2: RR =
2.22, HDI = 0.96-3.86). CONCLUSIONS: Our framework is effective at elucidating
multiple effects of volatile chemicals used in SR products, as well as their
downstream effects. For the examined formulations of transfluthrin, we found
notable dose-dependent effects on repellency, movement and knockdown that carry
over to adjacent, untreated spaces.
PMID- 29941039
TI - Sustained complete response of advanced hepatocellular carcinoma with metronomic
capecitabine: a report of three cases.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent causes of
cancer-related death. Sorafenib, a multitarget angiogenesis inhibitor, is an
approved frontline treatment for advanced HCC in Western countries, although a
complete response (CR) to treatment is infrequently reported. Capecitabine, an
oral fluoropyrimidine, has been shown to be effect in both treatment-naive
patients and those previously treated with sorafenib. To date, however, only one
case of sustained CR to metronomic capecitabine has been reported. CASE
PRESENTATION: We describe three cases of advanced HCC treated with metronomic
capecitabine where a CR was obtained. In the first case, capecitabine was
administered as first line therapy; in the second case, capecitabine was used
after intolerance to sorafenib; while in the third case, capecitabine was
administered after sorafenib failure. CONCLUSION: Capecitabine is a potentially
important treatment option for patients with advanced HCC and may even represent
a cure in certain cases.
PMID- 29941040
TI - Dose constraints in the rectum and bladder following carbon-ion radiotherapy for
uterus carcinoma: a retrospective pooled analysis.
AB - BACKGROUND: Carbon-ion radiotherapy (C-ion RT) provides better dose distribution
in cancer treatment compared to photons. Additionally, carbon-ion beams provide a
higher biological effectiveness, and thus a higher tumor control probability.
However, information regarding the dose constraints for organs at risk in C-ion
RT is limited. This study aimed to determine the predictive factors for late
morbidities in the rectum and bladder after carbon-ion C-ion RT for uterus
carcinomas. METHODS: Between June 1995 and January 2010, 134 patients with uterus
carcinomas were treated with C-ion RT with curative intent; prescription doses of
52.8-74.4 Gy (relative biological effectiveness) were delivered in 20-24
fractions. Of these patients, 132 who were followed up for > 6 months were
analyzed. We separated the data in two subgroups, a 24 fractions group and a 20
fractions group. Late morbidities, proctitis, and cystitis were assessed
according to the Radiation Therapy Oncology Group/European Organisation for
Research and Treatment of Cancer criteria. The correlations of clinical and
dosimetric parameters, V10-V60, D5cc, D2cc, and Dmax, with the incidence of
>=grade 1 morbidities were retrospectively analyzed. RESULTS: In the 24 fractions
group, the 3-year actuarial occurrence rates of >=grade 1 rectal and bladder
morbidities were 64 and 9%, respectively. In addition, in the 20 fractions group,
the 3-year actuarial occurrence rates of >=grade 1 rectal and bladder morbidities
were 32 and 19%, respectively. Regarding the dose-volume histogram data on the
rectum, the D5cc and D2cc were significantly higher in patients with >=grade 1
proctitis than in those without morbidity. In addition, the D5cc for the bladder
was significantly higher in patients with >=grade 1 cystitis than in those
without morbidity. Results of univariate analyses showed that D2cc of the rectum
was correlated with the development of >=grade 1 late proctitis. Moreover, D5cc
of the bladder was correlated with the development of >=grade 1 late cystitis.
CONCLUSIONS: The present study identified the dose-volume relationships in C-ion
RT regarding the occurrence of late morbidities in the rectum and bladder.
Assessment of the factors discussed herein would be beneficial in preventing late
morbidities after C-ion RT for pelvic malignancies. TRIAL REGISTRATION:
Retrospectively registered ( NIRS: 16-040 ).
PMID- 29941041
TI - Correction to: Retrospective dosimetry study of intensity-modulated radiation
therapy for nasopharyngeal carcinoma: measurement-guided dose reconstruction and
analysis.
AB - The original version of this article [1] unfortunately contained a mistake.
PMID- 29941042
TI - Parkinson's disease-associated protein Parkin: an unusual player in cancer.
AB - The mutation of the Parkin gene is a cause of familial Parkinson's disease. A
growing body of evidence suggests that Parkin also functions as a tumor
suppressor. Parkin is an ubiquitin E3 ligase, and plays important roles in a
variety of cellular processes implicated in tumorigenesis, including cell cycle,
cell proliferation, apoptosis, metastasis, mitophagy and metabolic reprogramming.
Here we review the role and mechanism of Parkin in cancer.
PMID- 29941043
TI - Translation of robot-assisted rehabilitation to clinical service: a comparison of
the rehabilitation effectiveness of EMG-driven robot hand assisted upper limb
training in practical clinical service and in clinical trial with laboratory
configuration for chronic stroke.
AB - BACKGROUND: Rehabilitation robots can provide intensive physical training after
stroke. However, variations of the rehabilitation effects in translation from
well-controlled research studies to clinical services have not been well
evaluated yet. This study aims to compare the rehabilitation effects of the upper
limb training by an electromyography (EMG)-driven robotic hand achieved in a well
controlled research environment and in a practical clinical service. METHODS: It
was a non-randomized controlled trial, and thirty-two participants with chronic
stroke were recruited either in the clinical service (n = 16, clinic group), or
in the research setting (n = 16, lab group). Each participant received 20-session
EMG-driven robotic hand assisted upper limb training. The training frequency (4
sessions/week) and the pace in a session were fixed for the lab group, while they
were flexible (1-3 sessions/week) and adaptive for the clinic group. The training
effects were evaluated before and after the treatment with clinical scores of the
Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), Functional
Independence Measure (FIM), and Modified Ashworth Scale (MAS). RESULTS:
Significant improvements in the FMA full score, shoulder/elbow and wrist/hand (P
< 0.001), ARAT (P < 0.001), and MAS elbow (P < 0.05) were observed after the
training for both groups. Significant improvements in the FIM (P < 0.05), MAS
wrist (P < 0.001) and MAS hand (P < 0.05) were only obtained after the training
in the clinic group. Compared with the lab group, higher FIM improvement in the
clinic group was observed (P < 0.05). CONCLUSIONS: The functional improvements
after the robotic hand training in the clinical service were comparable to the
effectiveness achieved in the research setting, through flexible training
schedules even with a lower training frequency every week. Higher independence in
the daily living and a more effective release in muscle tones were achieved in
the clinic group than the lab group.
PMID- 29941044
TI - Age exerts a continuous effect in the outcomes of Asian breast cancer patients
treated with breast-conserving therapy.
AB - BACKGROUND: Asians are diagnosed with breast cancer at a younger age than
Caucasians are. We studied the effect of age on locoregional recurrence and the
survival of Asian breast cancer patients treated with breast-conserving therapy.
METHODS: Medical records of 2492 patients treated with breast-conserving therapy
between 1989 and 2012 were reviewed. The Kaplan-Meier method was used to estimate
locoregional recurrence, breast cancer-free survival, and breast cancer-specific
survival rates. These rates were then compared using log-rank tests. Outcomes and
age were modeled by Cox proportional hazards. Fractional polynomials were then
used to test for non-linear relationships between age and outcomes. RESULTS:
Patients <= 40 years old were more likely to have locoregional recurrence than
were older patients (Hazard ratio [HR] = 2.32, P < 0.001). Locoregional
recurrence rates decreased year-on-year by 4% for patients with luminal-type
breast cancers, compared with 8% for those with triple-negative cancers.
Similarly, breast cancer-free survival rates increased year-on-year by 4% versus
8% for luminal-type and triple-negative cancers, respectively. Breast cancer
specific survival rates increased with age by 5% year-on-year. Both breast cancer
free survival and breast cancer-specific survival rates in patients with luminal
cancers exhibited a non-linear ("L-shaped") relationship-where decreasing age at
presentation was associated with escalating risks of relapse and death. The
influence of age on overall survival was confounded by competing non-cancer
deaths in older women, resulting in a "U-shaped" relationship. CONCLUSIONS: Young
Asian breast cancer patients have a continuous year-on-year increase in rates of
disease relapse and cancer deaths compared with older patients with no apparent
threshold.
PMID- 29941045
TI - Clonal amplification of Fasciola hepatica in Galba truncatula: within and between
isolate variation of triclabendazole-susceptible and -resistant clones.
AB - BACKGROUND: Fasciola hepatica is of worldwide significance, impacting on the
health, welfare and productivity of livestock and regarded by WHO as a re
emerging zoonosis. Triclabendazole (TCBZ), the drug of choice for controlling
acute fasciolosis in livestock, is also the drug used to treat human infections.
However TCBZ-resistance is now considered a major threat to the effective control
of F. hepatica. It has yet to be demonstrated whether F. hepatica undergoes a
genetic clonal expansion in the snail intermediate host, Galba truncatula, and to
what extent amplification of genotypes within the snail facilitates accumulation
of drug resistant parasites. Little is known about genotypic and phenotypic
variation within and between F. hepatica isolates. RESULTS: Six clonal isolates
of F. hepatica (3* triclabendazole-resistant, TCBZ-R and 3* triclabendazole
susceptible, TCBZ-S) were generated. Snails infected with one miracidium started
to shed cercariae 42-56 days post-infection and shed repeatedly up to a maximum
of 11 times. A maximum of 884 cercariae were shed by one clonally-infected snail
(FhLivS1) at a single time point, with > 3000 clonal metacercariae shed over its
lifetime. Following experimental infection all 12 sheep were FEC positive at the
time of TCBZ treatment. Sheep infected with one of three putative TCBZ-S clones
and treated with TCBZ had no parasites in the liver at post-mortem, whilst sheep
each infected with putative TCBZ-R isolates had 35-165 adult fluke at post
mortem, despite TCBZ treatment. All six untreated control animals had between 15
127 parasites. A single multi-locus genotype was reported for every fluke from
each of the six clonal isolates. Adult F. hepatica showed considerable variation
in weight, ranging from 20-280 mg, with variation in weight evident within and
amongst clonal isolates. CONCLUSIONS: A genetic clonal expansion occurs within G.
truncatula, highlighting the potential for amplification of drug resistant
genotypes of F. hepatica. Variation in the weight of parasites within and between
clonal isolates and when comparing isolates that are either susceptible or
resistant to TCBZ represent inherent variation in liver fluke and cannot be
attributed to their resistance or susceptibility traits.
PMID- 29941046
TI - Factors affecting development of Clostridium difficile infection in hospitalized
pediatric patients in the country Georgia.
AB - OBJECTIVE: Main aims of our study were to investigate occurrence of Clostridium
difficile among hospitalized pediatric patients in Georgia and examine risk
factors for the development of C. difficile infection. During our study we tested
and piloted the real-time PCR diagnostic systems for rapid and simultaneous
identification of C. difficile and number of other pathogens in our facility
settings. A cross-sectional study has been performed in children less than 18
years of age in two pediatric hospitals in Georgia, between May 2016 and December
2017. Stool specimens negative by the conventional bacteriology analysis were
analyzed for the presence of C. difficile and several viral and protozoa
pathogens using enzyme immune assay and polymerase chain reaction. In total
samples from 220 hospitalized children with gastroenteritis symptoms were
analyzed in this study. RESULTS: The average age of the study participants was
4.7 years. Overall 23 children were identified positive for C. difficile (10.5%).
Antibiotic exposure within 2 months preceding the onset of diarrhea was
associated with an increased risk of C. difficile infections. The risk was
greatest with cephalosporins, followed by penicillins, carbapenems and
macrolides. Clostridium difficile is an important cause of healthcare-associated
diarrhea in pediatric population of Georgia.
PMID- 29941048
TI - Differential expression of cytokines and receptor expression during anoxic
growth.
AB - OBJECTIVE: Cell density in tumor cell three dimensional (3D) cultures affects
secretome expression of components. A microenvironment characteristic shared by
high-density 3D cell culture and in vivo tumor masses is poor oxygenation, with
anoxia being a natural cell state in tumor centers. Until recently, the ability
to study anoxia-adapted cell physiology was not possible. Using a newly-developed
methodology, anoxic HeLa cell secretome expression was measured. RESULTS: Anoxic
HeLa cell cytokine levels after 3 days' (hypoxia inducible factor, HIF1 positive)
and 10 days' growth (HIF1 negative; anaerobic respiration) were significantly (p
< 0.01) higher than normoxic controls for: IL-8 (1.8- and 3.4-fold higher,
respectively), GRO (1.3- and 1.1-fold higher, respectively), and IL-11 (1.4- and
1.1-fold higher, respectively). In contrast, G-CSF, IFNalpha2, and CXCL-10 levels
decreased over time (day 3 vs. day 10). Thus, metabolically active HeLa cells
respond to the lack of oxygen, in part, by regulating the levels of cytokines
produced. Cytokines expressed at increased levels, in the absence of oxygen,
correspond to a secretomic profile reported for paracrine signaling pathways
associated with metastasis. Further studies defining physiologic changes that
occur upon anoxic growth may lead to the discovery of novel chemotherapeutic drug
targets.
PMID- 29941047
TI - A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in
adolescent patients with juvenile idiopathic arthritis.
AB - BACKGROUND: Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of
unknown etiology, which lasts for greater than 6 weeks with onset before 16 years
of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have
been the mainstay of initial management with naproxen (NAP) being commonly used,
but they may cause serious side effects such as gastric ulcers which can be
reduced by concomitant administration of proton pump inhibitors, such as
esomeprazole (ESO). METHODS: Primary objective was to evaluate the safety and
tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years.
Forty-six children and adolescents with JIA by International League of
Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites
were prospectively enrolled over 2 years and followed for up to 6 months. Doses
of the NAP/ESO fixed combination were based on baseline weight. The exploratory
efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90
Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and
functional scores at months 1, 3, and 6 as change from baseline. Occurrence and
causality were assessed for treatment emergent AEs (TEAEs) and discontinuations
were monitored monthly. RESULTS: Forty-six patients received at least 1 dose of
naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at
least 1 treatment emergent adverse event (TEAE) and, with the exception of 2
events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs
(>=5% of patients) were upper respiratory tract and gastrointestinal related.
Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four
patients (8.7%) discontinued due to a TEAE with one of these being the only
serious AE reported, acute hepatitis. Mean number of active joints at baseline
was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and
by month 6, the percentage of patients with an ACR Pediatric-30, - 50, - 70, and
90 Response was 47.1, 38.2, 32.4, and 17.6%, respectively. The percent of
patients achieving ACR Pediatric response increased over time. CHAQ discomfort
improved at each assessment and functional scores improved at all assessments for
'Arising, Walking, and Activities' with several improved for 'Dressing and
Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related
efficacy effect. CONCLUSION: NAP/ESO was well tolerated in JIA patients aged 12
to 16 years with high levels of response to ACR criteria. No new safety signals
were identified for the well-characterized components of this fixed dosed JIA
treatment, which was developed to reduce the risk of gastric ulcers. TRIAL
REGISTRATION: Clinicaltrials.gov, NCT01544114 . Registered February 21, 2012.
PMID- 29941049
TI - Significance of intra-fractional motion for pancreatic patients treated with
charged particles.
AB - BACKGROUND: Uncertainties associated with the delivery of treatment to moving
organs might compromise the accuracy of treatment. This study explores the impact
of intra-fractional anatomical changes in pancreatic patients treated with
charged particles delivered using a scanning beam. The aim of this paper is to
define the potential source of uncertainties, quantify their effect, and to
define clinically feasible strategies to reduce them. METHODS: The study included
14 patients treated at our facility with charged particles (protons or 12C) using
intensity modulated particle therapy (IMPT). Treatment plans were optimized using
the Treatment Planning System (TPS) Syngo(r) RT Planning. The pre-treatment dose
distribution under motion (4D) was simulated using the TPS TRiP4D and the dose
delivered for some of the treatment fractions was reconstructed. The volume
receiving at least 95% of the prescribed dose (V95CTV) and the target dose
homogeneity were evaluated. The results from the 4D dose calculations were
compared with dose distributions in the static case and its variation correlated
with the internal motion amplitude and plan modulation, through the Pearson
correlation coefficient, as well the significant p-value. The concept of the
modulation index (MI) was introduced to assess the degree of modulation of IMPT
plans, through the quantification of intensity gradients between neighboring
pencil beams. RESULTS: The induced breathing motion together with dynamic beam
delivery results in an interplay effect, which affects the homogeneity and target
coverage of the dose distribution. This effect is stronger (?V95CTV > 10%) for
patients with tumor motion amplitude above 5 mm and a highly modulated dose
distribution between and within fields. The MI combined with the internal motion
amplitude is shown to correlate with the target dose degradation and a lack of
plan robustness against range and positioning uncertainties. CONCLUSIONS: Under
internal motion the use of inhomogeneous plans results in a decrease in the dose
homogeneity and target coverage of dose distributions in comparison to the static
case. Plan robustness can be improved by using multiple beams and avoiding beam
entrance directions susceptible to density changes. 4D dose calculations support
the selection of the most suitable plan for the specific patient's anatomy.
PMID- 29941050
TI - In vitro activity of fluralaner and commonly used acaricides against Dermanyssus
gallinae isolates from Europe and Brazil.
AB - BACKGROUND: The poultry red mite Dermanyssus gallinae negatively impacts bird
welfare and health, and interferes with egg production and quality, while
emerging acaricide resistance limits control options. Fluralaner, a novel
miticide for administration in drinking water, is approved for control of D.
gallinae infestations. Mite sensitivity testing is relevant to gauge field
isolate susceptibility to available treatments. METHODS: Thirteen D. gallinae
isolates collected during 2014 through 2016 from farms in Germany, France, Spain
and Brazil, and a 2001 laboratory-maintained isolate were used for acaricide
contact sensitivity testing. Tested compounds were cypermethrin, deltamethrin,
phoxim, propoxur, and the recently available acaricides, spinosad and fluralaner.
In each study, at least one isolate was exposed to increasing concentrations of
at least one acaricide. In one study, additional testing determined the
sensitivity of the 2001 isolate to fluralaner using a mite-feeding test, and of
fluralaner, phoxim and spinosad using an immersion test. At least two replicates
were used for each dilution. Vehicle and untreated controls were also included.
RESULTS: Based on 90% mortality (LC90) values, the laboratory isolate was
susceptible to fluralaner (15.6-62.5 parts per million, ppm), phoxim (< 500 ppm),
propoxur (< 125 ppm), and deltamethrin (500-1000 ppm). All field isolates
remained sensitive to fluralaner concentrations <= 125 ppm. Spinosad LC90 values
for laboratory and field isolates ranged between 2000-4000 ppm. For phoxim,
relative to the laboratory isolate, there was reduced sensitivity of two German
isolates (LC90 up to 4000 ppm) and two French isolates (> 4000 ppm). An isolate
from Spain demonstrated reduced sensitivity to phoxim, propoxur and deltamethrin;
an isolate from Brazil showed reduced sensitivity to propoxur and cypermethrin.
Mite LC90 when exposed to fluralaner by blood feeding was < 0.1 ppm. CONCLUSIONS:
Contact sensitivity testing indicated apparent resistance to at least one of
phoxim, deltamethrin, cypermethrin and propoxur in 13 field isolates from Europe
and Brazil. All isolates were highly susceptible to fluralaner. Fluralaner was
approximately 1000 times more active by feeding than by contact. Fluralaner's
distinct mode of action and efficacy against isolates largely refractory to those
acaricides, makes it a promising option for the control of D. gallinae
infestations of poultry.
PMID- 29941051
TI - Endometriosis does not confer improved prognosis in ovarian clear cell carcinoma:
a retrospective study at a single institute.
AB - BACKGROUND: Considered as the precursor lesion of a subset of ovarian clear cell
carcinoma (OCCC), the prognostic role of endometriosis in OCCC patients remains
controversial. This study aimed to investigate the prognostic role of coexisting
endometriosis in the survival of patients with OCCC, and also sought to identify
other prognostic factors. RESULTS: A total of 125 patients were diagnosed with
OCCC during the study period. Of these, 55 (44.0%) patients had coexisting
endometriosis. Patients with endometriosis were younger (p = 0.030), had smaller
tumor diameter (p = 0.005) and lower preoperative CA125 levels (p = 0.005). More
patients with endometriosis had International Federation of Gynecology and
Obstetrics (FIGO) stage I disease (83.6% vs. 51.4%, p = 0.000) and exhibited
sensitivity to platinum-based regimen (89.6% vs. 66.7%, p = 0.003). Univariate
and multivariate analysis revealed that coexisting endometriosis was not a
predictor of 5-year overall survival (OS) or progression-free survival (PFS) of
OCCC patients. For OS, chemosensitivity was the only useful prognostic factor
(Hazards ratio (HR) 109.33, 95% Confidence Interval (CI) 23.46-511.51; p =
0.000). For PFS, the useful prognostic factors were ascites (HR 2.78, 95% CI 1.21
6.47; p = 0.016), FIGO stage (HR 1.61, 95% CI 1.04-2.49; p = 0.033), and
chemosensitivity (HR 101.60, 95% CI 29.45-350.49; p = 0.000). Moreover, higher
FIGO stage was the only risk factor for resistance to platinum-based chemotherapy
(Exp (B) = 0.292, 95% CI 0.123-0.693; p = 0.005). CONCLUSIONS: In this study,
coexisting endometriosis was not a prognostic factor for the survival of OCCC
patients. The most important predictor of both 5-year OS and PFS was
chemosensitivity to platinum-based regimen, which decreased significantly with
increase in FIGO stage.
PMID- 29941053
TI - Developmental changes of neuropsychological functioning in individuals with and
without childhood ADHD from early adolescence to young adulthood: a 7-year follow
up study.
AB - BACKGROUND: Our knowledge about the developmental change of neuropsychological
functioning in attention-deficit/hyperactivity disorder (ADHD) is limited. This
prospective longitudinal study examined the changes in neuropsychological
functions and their associations with the changes of ADHD symptoms across the
developmental stages from early adolescence to young adulthood. METHODS: We
followed up 53 individuals diagnosed with the Diagnostic and Statistical Manual
of Mental Disorders, Fourth Edition (DSM-IV) ADHD during childhood (mean age
12.77 years at time 1, 19.81 years at time 2) and 50 non-ADHD controls (mean age
12.80 years at time 1, 19.36 years at time 2) with repeated psychiatric
interviews at two time points to confirm ADHD and other psychiatric diagnoses.
Neuropsychological functions with high- and low-executive demands, measured by
the Cambridge Neuropsychological Testing Automated Battery (CANTAB) at two time
points, were compared. RESULTS: Both groups showed improvements in all
neuropsychological tasks except reaction time in the ADHD group. Despite having a
greater improvement in spatial working memory (SWM) than controls, individuals
with ADHD still performed worse in various neuropsychological tasks than controls
at follow-up. Better baseline intra-dimension/extra-dimension shift and parental
occupation predicted fewer ADHD symptoms at follow-up independent of baseline
ADHD symptoms. The degree of ADHD symptom reduction was not significantly
linearly correlated to the magnitude of neuropsychological function improvement.
CONCLUSION: Individuals with ADHD and controls had parallel developments in
neuropsychological functioning, except a catch-up in SWM in ADHD. Almost all
neuropsychological functions herein were still impaired in ADHD at late
adolescence/young adulthood. There may be a threshold (i.e. non-linear)
relationship between neuropsychological functioning and ADHD symptoms.
PMID- 29941052
TI - Causality and preventability assessment of adverse drug events of antibiotics
among inpatients having different lengths of hospital stay: a multicenter, cross
sectional study in Lahore, Pakistan.
AB - BACKGROUND: A large number of hospital admissions are attributed to adverse drug
reactions (ADRs) and they are the fifth leading cause of death worldwide. The
present study aimed to assess the causality and preventability of adverse drug
events (ADEs) of antibiotics among inpatients having different lengths of
hospital stay. METHODS: A prospective, observational study was conducted in four
tertiary-care public sector hospitals of Lahore, Pakistan. Study population
consisted of hospitalized patients who were prescribed one or more antibiotics.
Data were collected between 1st January, 2017 and 30th June, 2017 from 1249
patients. Naranjo score, modified Schumock and Thornton scale were used for
causality and preventability assessments, respectively. Medication errors (MEs)
were assessed by MEs tracking form. SPSS and Microsoft Excel were used for data
analysis. RESULTS: A total of 2686 antibiotics were prescribed to 1249 patients
and 486 ADEs were found. The preventability assessment revealed that most of the
ADEs (78.8%) were found among patients having long length of stay (LOS) in
hospital and were preventable (59.3% of the ADEs were definitely preventable
while 44.7% were probably preventable) and caused by MEs including wrong drug
(40.1%) and monitoring errors (25%). The errors were caused due to non-adherence
of policies (38.4%) and lack of information about antibiotics (32%). Most of the
non-preventable ADEs or ADRs among patients having long and short LOS in hospital
were "probable" (35.5%) and "possible" (35.8%), respectively. Logistic regression
analysis revealed that ADEs were significantly less among females (OR = 0.047,
95% CI = 0.018?0.121, p-value = < 0.001), patients aged 18?52 years (OR = 0.041,
95% CI = 0.013?0.130, p-value = < 0.001), patients with ARTIs (OR = 0.004, 95% CI
= 0.01-0.019, p-value = < 0.001), patients prescribed with 2 antibiotics per
prescription (OR = 0.455, 95% CI = 0.319?0.650, p-value = < 0.001) and patients
with long LOS (OR = 14.825, 95% CI = 11.198?19.627, p-value = < 0.001).
CONCLUSION: Antibiotics associated definitely preventable ADEs were more commonly
found in patients having long LOS in the inpatient departments because of MEs and
lack of proper pharmacovigilance system. The ADRs showed a probable and possible
causal association with both beta-lactams and non beta-lactams antibiotics.
PMID- 29941054
TI - Effects of new n-3 fatty acid sources on milk fatty acid profile and milk fat
properties in dairy cows.
AB - Feeding livestock with n-3 fatty acid (FA) sources (linseed, for example) is a
common strategy to improve lipid quality of meat and milk products. However, in
monogastric animals, linseed tegument decreases digestibility and alphalinolenic
acid (ALA) uptake, while the whole linseed is well used by ruminants. In a
context of increasing sustainability of feeding systems, providing monogastric
animals and ruminants with linseed products adapted to their digestive systems is
an important issue. This research paper addresses the hypotheses: (i) sieved
extruded linseed (SEL) specific for ruminants is as or more effective than
standard extruded linseed (ii) microalgae DHA Gold(r) is an interesting source of
docosahexaenoic acid (DHA) in feedstuff and (iii) the effects of SEL and
microalgae on milk characteristics are complementary and additive. Thirty-two
cows were divided into 4 groups with different dietary n-3 fatty acid sources
using a continuous design. All the diets were fed as mixed rations based on maize
silage, energy concentrate and soybean meal. The first group received a control
diet (CTRL) with no additional fat. The 3 other groups received SEL, microalgae
DHA Gold(r) (ALG) and a mixture of microalgae DHA Gold(r) and SEL (SEL/ALG). Milk
was collected from morning milkings after six weeks of dietary treatment. In SEL
and SEL/ALG, ALA increased (+0.32 and +0.26% unit, respectively), and DHA
increased in ALG and SEL/ALG (+0.43 and +0.15% unit, respectively) compared to
CTRL, as a consequence of the initial composition of the n-3 FA sources. In SEL,
milk yield, fat and protein contents, milk fat globule size and spontaneous
lipolysis (measured to evaluate suitability for milk processing) were not
different compared with CTRL. In ALG and SEL/ALG, milk yield decreased (-2.8 and
6.0 kg/d, respectively), fat content was halved, and fat globule size was reduced
(-1.46 and -1.31 um, respectively) compared to CTRL. Spontaneous lipolysis
increased in ALG (+0.12 mEq/kg of milk) compared to CTRL. Protected microalgae
and the doses of microalgae in the diet need further investigation to prevent FA
modification in the rumen and the consequent deleterious effects on milk fat.
PMID- 29941056
TI - Q fever: an under-reported reportable communicable disease.
AB - The objective of this study was to provide real-world clinical laboratory-based
data to supplement Centers for Disease Control and Prevention (CDC) reporting of
Q fever. We analysed titre results of specimens submitted to a large US clinical
laboratory for Coxiella burnetii IgG antibody testing from 2010 through 2016.
Presumptive Q fever was defined as acute (phase II IgG titre ?1:128, phase I
titre <1:1024) or chronic (phase I IgG titre ?1:1024), based on the results from
a single serum specimen. During 2010-2016, an average of 328 presumptive acute Q
fever cases were identified at Quest each year, nearly three times the annual
average reported to the CDC (122). During the same period, the number of chronic
cases identified annually at Quest Diagnostics (34) was similar to that reported
to the CDC (29). These findings suggest that CDC data may underestimate the
incidence of acute Q fever.
PMID- 29941055
TI - A systematic scoping review of psychological therapies for psychosis within acute
psychiatric in-patient settings.
AB - BACKGROUND: People with psychotic disorders account for most acute admissions to
psychiatric wards. Psychological therapies are a treatment adjunct to standard
medication and nursing care, but the evidence base for such therapies within in
patient settings is unclear.AimsTo conduct a systematic scoping review of the
current evidence base for psychological therapies for psychosis delivered within
acute in-patient settings (PROSPERO: CRD42015025623). METHOD: All study designs,
and therapy models, were eligible for inclusion in the review. We searched
PubMed, PsycINFO, EThOS, ProQuest, conference abstracts and trial registries.
RESULTS: We found 65 studies that met criteria for inclusion in the review, 21 of
which were randomised controlled trials (RCTs). The majority of studies evaluated
cognitive-behavioural interventions. Quality was variable across all study types.
The RCTs were mostly small (n<25 in the treatment arm), and many had
methodological limitations including poorly described randomisation methods,
inadequate allocation concealment and non-masked outcome assessments. We found
studies used a wide range of different outcome measures, and relatively few
studies reported affective symptoms or recovery-based outcomes. Many studies
described adaptations to treatment delivery within in-patient settings, including
increased frequency of sessions, briefer interventions and use of single-session
formats. CONCLUSIONS: Based on these findings, there is a clear need to improve
methodological rigour within in-patient research. Interpretation of the current
evidence base is challenging given the wide range of different therapies, outcome
measures and models of delivery described in the literature.Declaration of
interestNone.
PMID- 29941057
TI - Switching stable patients with schizophrenia from their oral antipsychotics to
aripiprazole lauroxil: a post hoc safety analysis of the initial 12-week
crossover period.
AB - OBJECTIVE: Switching antipsychotic medications is common in patients with
schizophrenia who are experiencing persistent symptoms or tolerability issues
associated with their current drug regimen. This analysis assessed the safety of
switching from an oral antipsychotic to the long-acting injectable antipsychotic
aripiprazole lauroxil (AL). METHODS: This was a post hoc analysis of outpatients
with schizophrenia who were prescribed an oral antipsychotic and who enrolled in
an international, open-label, long-term (52-week) safety study of AL. The
analysis focused on the first 3 injections of AL 882 mg over 12 weeks, divided
into the immediate 4-week crossover period between the first and second AL
injections (initiation phase) and the subsequent 8 weeks (stabilization phase).
Patients were grouped by preswitch oral antipsychotic medication, and safety and
clinical symptoms were assessed. RESULTS: In total, 190 patients had switched
from one of the following oral antipsychotic medications: aripiprazole,
conventional antipsychotics, risperidone/paliperidone, olanzapine, or quetiapine.
The 12-week completion rate was high (92.1%) and similar across the different
preswitch oral antipsychotic groups. Overall, adverse event (AE) rates
experienced over 12 weeks were modest; no AEs were considered serious. The most
common AEs in the initiation phase were injection site pain (5.8%), insomnia
(5.8%), and akathisia (3.2%). No apparent relationship was observed between
preswitch medication and early-onset AEs. Mean Positive and Negative Syndrome
Scale total scores remained stable during this period across preswitch
antipsychotic groups. CONCLUSION: Switching from an oral antipsychotic to AL was
feasible in an outpatient setting for patients with schizophrenia, and the 12
week retention rate was favorable.
PMID- 29941058
TI - Communicating terminal prognosis: The provider's role in reframing hope.
PMID- 29941060
TI - PROGRESS AND PROSPECTS OF HEALTH-RELATED SUSTAINABLE DEVELOPMENT GOALS IN INDIA.
AB - SummaryThe Sustainable Development Goals (SDGs) are increasingly being used to
measure developmental progress among and within countries. Achieving the health
related SDGs remains a primary concern of many developing countries. This study
measured the progress in selected health-related indicators of SDGs in the states
of India by social and economic groups, and predicted their likely progress by
2030. The health indicators analysed included health outcomes, nutrition, health
care utilization and determinants of health. Data from the Census of India,
Sample Registration System (SRS), National Family and Health Surveys (NFHSs) and
National Sample Survey Organization (NSSO) were used in the analysis. Annual rate
of progress (ARP) and the required rate of progress (RRP) were computed for
selected indicators over the period 2005-06 to 2015-16. A Composite Index of
Health (CIH) was used to understand the state of health of populations. The ARP
was higher than the RRP in maternal care and reduction of under-five mortality,
while ARP was lower than the RRP in undernutrition and sanitation. The ARP for
health-related indicators showed a mixed pattern across religion and caste
groups. The ARP for medical assistance at birth and immunization was highest
among Scheduled Castes and that for reduction of under-five mortality was highest
among Scheduled Tribes. The CIH was lowest in Uttar Pradesh (0.26) and highest in
Goa (0.81). The association between the CIH and the Human Development Index (HDI)
was significant, suggesting interlinkage between health and development. Notable
improvements were observed in maternal and child health and maternal health care
utilization across social groups in India over the period 2005-06 to 2015-16, and
if the trends continue the country can achieve the SDG target in maternal health
by 2030. However, progress in nutrition and other health indicators has been slow
and uneven.
PMID- 29941059
TI - Peroxisome proliferator-activated receptor beta/delta does not regulate glucose
uptake and lactose synthesis in bovine mammary epithelial cells cultivated in
vitro.
AB - The hypothesis of the study was that inhibition of PPARbeta/delta increases
glucose uptake and lactose synthesis in bovine mammary epithelial cells by
reducing the expression of the glucose transporter mRNA destabiliser
calreticulin. Three experiments were conducted to test the hypothesis using
immortalised bovine mammary alveolar (MACT) and primary bovine mammary (PBMC)
cells. In Experiment 1, the most effective dose to inhibit PPARbeta/delta
activity among two synthetic antagonists (GSK-3787 and PT-s58) was assessed using
a gene reporter assay. In Experiment 2, the effect on glucose uptake and lactose
synthesis was evaluated by measuring glucose and lactose in the media and
expression of related key genes upon modulation of PPARbeta/delta using GSK-3787,
the synthetic PPARbeta/delta agonist GW-501516, or a combination of the two in
cells cultivated in plastic. In Experiment 3, the same treatments were applied to
cells cultivated in Matrigel and glucose and lactose in media were measured. In
Experiment 1 it was determined that a significant inhibition of PPARbeta/delta in
the presence or absence of fetal bovine serum was achieved with >= 1000 nm GSK
3787 but no significant inhibition was observed with PT-s58. In Experiment 2,
inhibition of PPARbeta/delta had no effect on glucose uptake and lactose
synthesis but they were both increased by GW-501516 in PBMC. The mRNA abundance
of PPARbeta/delta target gene pyruvate dehydrogenase kinase 4 was increased but
transcription of calreticulin was decreased (only in MACT cells) by GW-501516.
Treatment with GSK-3787 did not affect the transcription of measured genes. No
effects on glucose uptake or lactose synthesis were detected by modulation of
PPARbeta/delta activity on cells cultivated in Matrigel. The above data do not
provide support for the original hypothesis and suggest that PPARbeta/delta does
not play a major role in glucose uptake and lactose synthesis in bovine mammary
epithelial cells.
PMID- 29941061
TI - Peripheral arterial catheter colonization in cardiac surgical patients.
PMID- 29941062
TI - Acceptance and Commitment group Therapy for patients with multiple functional
somatic syndromes: a three-armed trial comparing ACT in a brief and extended
version with enhanced care.
AB - BACKGROUND: Psychological treatment for functional somatic syndromes (FSS) has
been found moderately effective. Information on how much treatment is needed to
obtain improvement is sparse. We assessed the efficacy of a brief and extended
version of group-based Acceptance and Commitment Therapy (ACT) v. enhanced care
(EC) for patients with multiple FSS operationalised as Bodily Distress Syndrome
multi-organ type. METHODS: In a randomised controlled three-armed trial,
consecutively referred patients aged 20-50 with multiple FSS were randomly
assigned to either (1) EC; (2) Brief ACT: EC plus 1-day workshop and one
individual consultation; or (3) Extended ACT: EC plus nine 3-h group-based
sessions. Primary outcome was patient-rated overall health improvement on the
five-point clinical global improvement scale 14 months after randomisation. A
proportional odds model was used for the analyses. RESULTS: A total of 180
patients were randomised; 60 to EC, 61 to Brief ACT, and 59 to Extended ACT.
Improvement on the primary outcome after Extended ACT was significantly greater
than after EC with an unadjusted OR of 2.9 [95% CI (1.4-6.2), p = 0.006]. No
significant differences were found between Brief ACT and EC. Of the 18 secondary
outcomes, the only significant difference found was for physical functioning in
the comparison of Extended ACT with EC. CONCLUSIONS: Patients rated their overall
health status as more improved after Extensive ACT than after EC; however,
clinically relevant secondary outcome measures did not support this finding.
Discrepancies between primary and secondary outcomes in this trial are discussed.
PMID- 29941063
TI - Patient Presentation Trends at 15 Mass-Gathering Events in South Australia.
AB - : IntroductionMass gatherings are complex events that present a unique set of
challenges to attendees' health and well-being. There are numerous factors that
influence the number and type of injuries and illnesses that occur at these
events, including weather, event and venue type, and crowd demographics and
behavior.ProblemWhile the impact of some factors, such as weather conditions and
the availability of alcohol, on patient presentations at mass gatherings have
been described previously, the influence of many other variables, including crowd
demographics, crowd behavior, and event type, is poorly understood. Furthermore,
a large number of studies reporting on the influence of these variables on
patient presentations are based on anecdotal evidence at a single mass-gathering
event. METHODS: Data were collected by trained fieldworkers at 15 mass gatherings
in South Australia and included event characteristics, crowd demographics, and
weather. De-identified patient records were obtained from on-site health care
providers. Data analysis included the calculation of patient proportions in each
variable category, as well as the total number of patient presentations per event
and the patient presentation rate (PPR). RESULTS: The total number of expected
attendees at the 15 mass gatherings was 303,500, of which 146 presented to on
site health care services. The majority of patient presentations occurred at
events with a mean temperature between 20 degrees C and 25 degrees C. The PPR was
more than double at events with a predominantly male crowd compared to events
with a more equal sex distribution. Almost 90.0% of patient presentations
occurred at events where alcohol was available. CONCLUSION: The results of the
study suggest that several weather, crowd, and event variables influence the type
and number of patient presentations observed at mass-gathering events. Given that
the study sample size did not allow for these interactions to be quantified,
further research is warranted to investigate the relationships between alcohol
availability, crowd demographics, crowd mobility, venue design, and injuries and
illnesses.Anikeeva O, Arbon P, Zeitz K, Bottema M, Lund A, Turris S, Steenkamp M.
Patient presentation trends at 15 mass-gathering events in South Australia.
Prehosp Disaster Med. 2018;33(4):368-374.
PMID- 29941064
TI - National outbreak of Salmonella Give linked to a local food manufacturer in
Malta, October 2016.
AB - Salmonella Give is a rare serotype across Europe. In October 2016, a national
outbreak of S. Give occurred in Malta. We describe the epidemiological,
environmental, microbiological and veterinary investigations. Whole-genome
sequencing (WGS) was performed on human, food, environmental and veterinary
isolates. Thirty-six human cases were reported between October and November 2016,
10 (28%) of whom required hospitalisation. Twenty-six (72%) cases were linked to
four restaurants. S. Give was isolated from ready-to-eat antipasti served by
three restaurants which were all supplied by the same local food manufacturer.
Food-trace-back investigations identified S. Give in packaged bean dips, ham,
pork and an asymptomatic food handler at the manufacturer; inspections found
inadequate separation between raw and ready-to-eat food during processing. WGS
indicated two genetically distinguishable strains of S. Give with two distinct
clusters identified; one cluster linked to the local food manufacturer and a
second linked to veterinary samples. Epidemiological, environmental and WGS
evidence pointed towards cross-contamination of raw and ready-to-eat foods at the
local manufacturer as the likely source of one cluster. Severity of illness
indicates a high virulence of this specific serotype. To prevent future cases and
outbreaks, adherence to food safety practices at manufacturing level need to be
reinforced.
PMID- 29941065
TI - Pain-related distress among patients referred to a community-based palliative
care program.
AB - OBJECTIVE: Numerous studies have characterized the pain reported by patients with
advanced illness in terms of descriptors such as severity, but few have measured
pain-related distress. Distress may be important in the clinical approach to
pain. To evaluate pain-related distress among adult patients with advanced
illness and pain following enrollment in an urban, specialist-level, community
based palliative care program. METHOD: In a retrospective cross-sectional
analysis, data were extracted from the electronic health records of all patients
who were able to complete the pain item from the Condensed Memorial Symptom
Assessment Scale at the start of care. Bivariate and multivariate analyses
evaluated the associations between distress and both sociodemographics and
disease-related information. RESULTS: The 506 patients completing the pain item
had a mean (SD) age of 70.7 years (13.8); 64.2% were women, 32.1% were Hispanic,
32.6% were white, and 27.7% were black. Of the 503 patients who indicated some
level of distress on a 0-4 scale, 221 (43.7%) had high distress, defined as a
score >=3 ("quite a bit" or "very much"). Cancer diagnosis and poor performance
status (unable to care for self) were predictors of high pain-related distress
(both p < 0.05).Significance of resultsAmong patients with advanced illness who
reported pain at the start of care by a specialist palliative care program, high
pain-related distress was common, particularly among those with cancer or poor
physical function. Further studies are needed to explore the extent to which pain
related distress should inform the assessment and management of pain.
PMID- 29941067
TI - Advancing microbiome research.
PMID- 29941066
TI - Geography but not alternative host species explain the spread of raccoon rabies
virus in Vermont.
AB - In North America, the raccoon-associated variant of rabies virus (RRV) is of
special concern, given its relatively rapid spread throughout the eastern USA and
its potential public health impact due to high raccoon host densities in urban
areas. Northward expansion of this epizootic included an outbreak in the Canadian
province of Quebec in 2006-2009 due to trans-border spread from the State of
Vermont. To inform a more proactive approach to future control efforts, this
study uses phylogenetic analyses to explore the role of geography and alternative
carnivore hosts in the dynamics of RRV spread within Vermont. Specifically, we
sought to examine whether striped skunks, a species frequently infected by RRV,
could be part of the maintenance host community. Whole genome sequencing of 160
RRV samples from Vermont and neighbouring US states were used for fine-scale
phylogeographic analyses. Results, together with the complete surveillance record
of raccoon rabies since its entry into Vermont in 1994, document incursions by
two distinct viral lineages and identify topographical features of the landscape
which have significantly influenced viral spread, resulting in a complex
distribution pattern of viral variants throughout the state. Results of
phylogenetic cluster analysis and discrete state reconstruction contained some
evidence of skunk-to-skunk and skunk-to-raccoon transmission but overall failed
to support a role for skunks as alternative maintenance hosts.
PMID- 29941069
TI - Editorial.
PMID- 29941070
TI - The Disobeying 'Soldier': Use of an Achiral Group to Modulate Chiral Induction in
PNA Duplexes.
AB - Peptide nucleic acid (PNA) is a synthetic analogue of DNA in which the natural
nucleobases A, G, C, and T are linked to an achiral, charge neutral,
pseudopeptide backbone. PNA strands can form double helices similar to DNA whose
helical sense can be modulated by applying the 'sergeants-and-soldiers'
principle. Attachment of a chiral amino acid (sergeant) at the C-terminus of PNA
leads to the amplification of chirality of the sergeant onto the achiral PNA
monomers (soldiers), resulting in an enantiomeric excess of either left- or right
handed PNA duplexes. In the present study we looked at the effect of an achiral N
terminal terpyridine (soldier) on the helicity of the double helix that contains
L-lysine. We have found that terpyridine interferes with the
chiral induction effect of the L-lysines, an effect that can be
reverted upon coordination of Cu2+ ions to terpyridine.
PMID- 29941071
TI - Towards Ultracold Chiral Molecules.
AB - Atoms can be cooled and trapped efficiently with the help of lasers. So-called
Doppler cooling takes advantage of momentum transfer upon absorption and emission
of photons and of Doppler shifts to facilitate effectively closed optical
absorption-emission loops, by which atoms are slowed down and cooled. Due to the
wealth of internal degrees of freedom accessible in molecules, it was assumed for
a long time that similarly closed optical loops cannot be realised for molecules.
After an early theoretical proposal by Di Rosa for diatomic molecules, such
cooling has been achieved in this decade for SrF, YO, CaF and YbF. It has been
outlined recently that also polyatomic molecules should be coolable with lasers
and classes of molecules expected to be amenable to this have been proposed by
the present authors. Experimental success in laser cooling of SrOH has been
reported. The status of cooling polyatomic molecules with lasers and the
prospects for obtaining ultracold chiral molecules is reviewed herein.
PMID- 29941072
TI - Optical Chiral Induced Spin Selectivity XMCD Study.
AB - The chiral induced spin selectivity (CISS) effect in which selective transport of
electron spins through helical chiral molecules occurs, has attracted a lot of
attention in recent years. This effect was used to magnetize ferromagnetic (FM)
samples by utilizing adsorbed chiral molecules. The electron transfer through the
molecules was generated optically or electrically. In the optical configuration,
circularly polarized light induced efficient magnetization by spin torque
transfer (STT), using a hybrid of quantum dots (QDs) and chiral molecule self
assembled monolayer (SAM). Here, we use X-ray magnetic chiral dichroism (XMCD)
spectroscopy in order to probe the optically induced magnetization on thin FM
films. The results show differences in the FM magnetization depending on the
optical circular polarization, matching previous non-local Hall probe
measurements.
PMID- 29941073
TI - Investigating Absolute Stereochemical Configuration with Coulomb Explosion
Imaging.
AB - It is a particularly challenging task in stereochemistry to determine the
absolute configuration of chiral molecules, i.e. to assign to a given sample the
microscopic enantiomeric structure. In recent years, Coulomb Explosion Imaging
(CEI) has been shown to yield directly the absolute configuration of small
molecules in the gas phase. This contribution describes the experimental basics
of this approach, highlights the most significant results and discusses
limitations. A short discussion on extending Coulomb Explosion Imaging beyond
analytic aspects to fundamental questions of molecular chirality concludes this
review.
PMID- 29941074
TI - Conformational Study and Chiroptical Properties of Chiral Dimethyl-Ethylenedithio
Tetrathiafulvalene (DM-EDT-TTF).
AB - The enantiopure dimethyl-ethylenedithio-tetrathiafulvalene (DM-EDT-TTF) donor
exists as biaxial (ax, ax) and biequatorial (eq, eq) conformers in equilibrium.
DFT calculations combined with free energy surface (FES) analysis establish that
the (ax, ax) form is more stable by ~0.7 kcal.mol-1 than the (eq, eq) one and
that the inter-conversion process involves a sequential conformational change
through a boat type (ax, eq) conformer with an activation energy of ~3 kcal.mol
1. TD-DFT calculations show similar, but opposite in sign, CD bands for the two
conformers. A Boltzmann type average of the two CD curves, corresponding to a
ratio of three (ax, ax) for one (eq, eq) conformers in equilibrium in solution,
provides an excellent agreement with the experimental curve.
PMID- 29941075
TI - Chirality and Spin: A Different Perspective on Enantioselective Interactions.
AB - This review describes a new perspective on the role that electron spin plays in
the intermolecular forces between two chiral molecules and between chiral
molecules and surfaces. This different role of the spin arises from the chiral
induced spin selectivity (CISS) effect which is manifest when electrons are
moving in chiral molecules. Namely, it has been shown that as chiral molecules
are charge polarized, the electron displacement is accompanied by spin
polarization. The spin direction associated with each electric pole depends on
the specific handedness of the molecule. Thus, the consideration of the
dispersive forces between two molecules, or between a molecule and a substrate,
must include the spin polarization which adds an enantioselective electronic term
to the interaction potential. We review recent experiments that show the relation
between charge polarization and spin polarization in chiral molecules. The spin
polarization also affects the direction of the ferromagnetic substrate magnetic
moment of a surface, upon which the chiral molecules are adsorbed.
PMID- 29941076
TI - On the Density of Racemic and Homochiral Crystals: Wallach, Liebisch and
Sommerfeld in Gottingen.
AB - The first comparison of heterochiral crystals with their homochiral counterparts
was given by Otto Wallach in an account on carvone bromide crystals in 1895 in
Liebigs Annalen der Chemie. Although the well-known mineralogist Theodor
Liebisch, professor in Gottingen from 1887 to 1908, performed the analyses and
wrote the last four pages of that Annalen paper, his colleague from chemistry,
Wallach served as sole author. We discuss whether Wallach or Liebisch had the
idea of a comparative study of crystal densities of racemates and their
homochiral analogues and who of the two should be credited.
PMID- 29941077
TI - Enantiospecific Adsorption and Decomposition of D- and L-Asp Mixtures on
Cu(643)R&S.
AB - The study of molecular chirality is essential to understanding the fundamentals
of enantiospecific chemical interactions that are ubiquitous in the biochemistry
of life on Earth. At a molecular level, there is insufficient understanding of
chiral recognition and enantiomer-enantiomer interaction (aggregation) of chiral
molecules adsorbed on surfaces. Here, using enantiospecific isotopic labelling
and surface sensitive techniques, we show that when the two enantiomers of chiral
aspartic acid (Asp) are adsorbed on the naturally chiral Cu(643)R&S surfaces,
they decompose enantiospecifically depending on the chirality of the surface. The
non-linear kinetics of the surface decomposition mechanism amplifies the
difference between the decomposition rate constants of the two adsorbed
enantiomers resulting in highly enantiospecific decomposition rates. Further, we
also demonstrate that Asp enantiomers aggregate homochirally on several chiral
and achiral surfaces, amplifying the enantiomeric excess on the surface with
respect to that in the gas phase, |ees |>|eeg. Our results show that it is
possible to discern the enantiospecific behavior of a complex adsorbate such as
Asp and shed light on molecular level enantiospecific interactions on surfaces.
The enantiospecific isotope labelling methods discussed in this paper allow
probing of both the qualitative features of the Asp decomposition mechanism on
Cu(643)R&S and quantitative aspects of the adsorption equilibria of enantiomer
mixtures.
PMID- 29941078
TI - Spin-orbit Coupling Modulation in DNA by Mechanical Deformations.
AB - We consider molecular straining as a probe to understand the mobility and spin
active features of complex molecules. The strength of the spin-orbit interaction
relevant to transport in a low dimensional structure depends critically on the
relative geometrical arrangement of current-carrying orbitals. Understanding the
origin of the enhanced spin-orbit interaction in chiral systems is crucial to be
able to control the spin selectivity observed in the experiments, which is a
hallmark of the Chiral-Induced Selectivity Effect (CISS). Recent tight-binding
orbital models for spin transport in DNA-like molecules, have surmised that the
band spin-orbit (SO) coupling arises from the particular angular relations
between orbitals of neighboring bases on the helical chain. Such arrangements
could be probed by straining the molecule in a conductive probe AFM/Break
junction type setup, as was recently reported by Kiran, Cohen and Naaman. Here we
report strain-dependent kinetic and SO coupling when a double-strand DNA model is
compressed or stretched in two experimentally feasible setups with peculiar
deformation properties. We find that the mobility and the SO coupling can be
tuned appreciably by strain, and the analytical model bears out the qualitative
trends of the experiments.
PMID- 29941079
TI - Enantiosensitive Bonding of Chiral Molecules on a Magnetic Substrate Investigated
by Means of Electron Spectroscopies.
AB - The adsorption of purely organic chiral molecules on ferromagnetic Co thin films
is studied under ultra high vacuum conditions by means of synchrotron radiation
based electron spectroscopies, namely X-ray absorption and ultraviolet
photoemission. X-ray absorption reveals that enantiomers with opposite handedness
(R,R)- and (S,S)- of two different molecules adsorb with different strength on
the Co surfaces and their valence band photoemission spectra also display
distinctive features. In view of the recent reports describing the chiral-induced
spin selectivity (CISS) effect these results lead us to consider the possibility
that some enantiosensitivity may appear when bonding chiral molecules to a
substrate with an initial asymmetry in the population of the different spin
orientations.
PMID- 29941081
TI - Analyzing Breath with Chemical Sensors.
PMID- 29941082
TI - Drugs Based on de novo-developed Peptides are Coming of Age mune is a.
AB - Naturally evolved peptides, such as the hormone oxytocin or the anti-bacterial
vancomycin, have seen decades of success as powerful therapeutics due to many of
the favorable properties of peptides. Not every desired target has a naturally
occurring bioactive peptide, so rational design and random in vitro evolution
techniques have been developed and applied to generate peptide leads de novo.
However, can these artificially created peptides be translated into successful
therapeutics? Several drug development programs involving de novo-generated
peptide ligands have made important progress recently, and we report here on
these exciting activities.
PMID- 29941083
TI - Geckos, Ceilings and van der Waals.
AB - The ability of a gecko to run rapidly across ceilings and up and down vertical
walls is a striking example of the application of van der Waals interactions.
PMID- 29941084
TI - The New, Stringent MDR and IVDR Regulations: Viewing this Change as an
Opportunity.
AB - The healthcare and life science sector is growing inexorably, and is now a multi
billion dollar industry. In 2016 the companies in this sector posted sales of USD
140 billion, and their profitability more than doubled by comparison with 2010.
The pharmaceutical, diagnostics, medtech and chemical sectors have become
Switzerland's most powerful export industry, and significant number of approved
medications and diagnostics contain biotech elements.
PMID- 29941085
TI - Conference Report.
PMID- 29941086
TI - Conference Report.
PMID- 29941087
TI - Conference Report.
PMID- 29941088
TI - CHIMIA Report/Company News.
PMID- 29941089
TI - Erratum to: PD-1 deficiency protects experimental colitis via alteration of gut
microbiota.
AB - The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 50(11):
578-583 titled "PD-1 deficiency protects experimental colitis via alteration of
gut microbiota."
PMID- 29941093
TI - Giving Credit where Credit Is Due (and Assigning Individual Responsibilities).
PMID- 29941091
TI - The human leukemia virus HTLV-1 alters the structure and transcription of host
chromatin in cis.
AB - Chromatin looping controls gene expression by regulating promoter-enhancer
contacts, the spread of epigenetic modifications, and the segregation of the
genome into transcriptionally active and inactive compartments. We studied the
impact on the structure and expression of host chromatin by the human retrovirus
HTLV-1. We show that HTLV-1 disrupts host chromatin structure by forming loops
between the provirus and the host genome; certain loops depend on the critical
chromatin architectural protein CTCF, which we recently discovered binds to the
HTLV-1 provirus. We show that the provirus causes two distinct patterns of
abnormal transcription of the host genome in cis: bidirectional transcription in
the host genome immediately flanking the provirus, and clone-specific
transcription in cis at non-contiguous loci up to >300 kb from the integration
site. We conclude that HTLV-1 causes insertional mutagenesis up to the megabase
range in the host genome in >104 persistently-maintained HTLV-1+ T-cell clones in
vivo.
PMID- 29941094
TI - Research Techniques Made Simple: Web-Based Survey Research in Dermatology:
Conduct and Applications.
AB - Web-based surveys, or e-surveys, are surveys designed and delivered using the
internet. The use of these survey tools is becoming increasingly common in
medical research. Their advantages are appealing to surveyors because they allow
for rapid development and administration of surveys, fast data collection and
analysis, low cost, and fewer errors due to manual data entry than telephone or
mailed questionnaires. Internet surveys may be used in clinical and academic
research settings with improved speed and efficacy of data collection compared
with paper or verbal survey modalities. However, limitations such as potentially
low response rates, demographic biases, and variations in computer literacy and
internet access remain areas of concern. We aim to briefly describe some of the
currently available Web-based survey tools, focusing on advantages and
limitations to help guide their use and application in dermatologic research.
PMID- 29941090
TI - Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive
modulation of fear memory by stress.
AB - Glucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced
high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key
structure underlying auditory-cued fear conditioning. Here, we demonstrate that
genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear
memory deficit for strengthened conditioning. Furthermore, the suppressive effect
of a single restraint stress (RS) prior to conditioning on auditory-cued fear
memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic
induction of long-term depression (LTD) at auditory inputs to the LA reduced
auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic
induction of long-term potentiation (LTP) increased auditory-cued fear memory in
RS-exposed floxed GR mice. These findings suggest that prior stress suppresses
fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent
manner, thereby protecting animals from encoding excessive cued fear memory under
stress conditions.
PMID- 29941095
TI - What's Eating the Epidermis? In Vivo Autophagy Manipulation via Subcutaneous
MicroRNA Delivery.
AB - Autophagy, discovered as a starvation-induced cellular recycling pathway, routes
protein aggregates, damaged organelles, and pathogens to lysosomes and also
supports normal tissue homeostasis. Although prior studies linked autophagy to
epidermal differentiation, infection, and carcinogenesis, Wang et al. report
upstream regulation of autophagy by microRNAs. Subcutaneous delivery of microRNA
mimics and antagonists modulated autophagy in vivo, suggesting a novel potential
therapeutic strategy in dermatology.
PMID- 29941096
TI - Tanning Addiction in Adolescents: Directions for Measurement and Intervention
Development.
AB - Little is known about tanning addiction in adolescents. Miller et al. found that
7.0% of 11th grade students met addiction criteria. After adjusting for all other
comorbidities, the odds of addiction were two times greater for students who
reported problem use of marijuana or obsessive-compulsive disorder symptoms. The
likelihood of addiction increased with problem substance use and psychological
symptoms.
PMID- 29941097
TI - IL-17C: A Unique Epithelial Cytokine with Potential for Targeting across the
Spectrum of Atopic Dermatitis and Psoriasis.
AB - Both atopic dermatitis (AD) and psoriasis are characterized by complex
inflammatory circuits that may be regulated through "feed-forward" mechanisms in
the epidermis that amplify cellular immune responses through production of
keratinocyte-derived cytokines and inflammatory mediators. IL-17C is a unique
cytokine that is produced by keratinocytes and that is involved in such
synergistic loops that may be responsible for amplifying the inflammation in both
diseases. This may ultimately lead to induction of S100As and other molecules
that accompany epidermal hyperplasia. Thus, antagonism of IL-17C may be
beneficial in both psoriasis and AD patients. The IL-17C neutralizing antibody
MOR 106 was able to inhibit both T helper type 2 cells and T helper type 17/T
helper type 22-skewed inflammatory loops that drive different features of AD and
psoriasis. The therapeutic potential of IL-17C antagonism in AD is supported by a
recently reported small phase 1 clinical trial in patients with AD.
PMID- 29941098
TI - Next Time, Save Mushrooms for the Pizza!
AB - Mann et al. (2018) use recombinant human tyrosinase to screen for novel
inhibitors of pigmentation. They develop thiamidol, a new thiazolyl-resorcinol
derivative, that is a submicromolar tyrosinase inhibitor and effective for
treating solar lentigines. Thiamidol and established inhibitors of pigmentation
exhibit substantially different activities on human and mushroom tyrosinase,
supporting use of the human enzyme in high-throughput screens.
PMID- 29941099
TI - SnapshotDx Quiz: July 2018.
PMID- 29941100
TI - Cells to Surgery Quiz: July 2018.
PMID- 29941101
TI - Exosomes as Theranostics for Lung Cancer.
AB - Extensive research in genetics and genomics has revealed that lung cancer is a
physiologically complex and genetically heterogeneous disease. Although molecular
targets that can yield favorable response have been identified, those targets
cannot be exploited due to the lack of suitable drug carriers. Furthermore, lung
cancer often is diagnosed at an advanced stage when the disease has metastasized.
Conventional treatments are not effective for treating metastatic lung cancer.
Targeted therapeutics while beneficial has challenges that include poor tumor
targeting, off-target effects, and development of resistance to therapy.
Therefore, improved drug delivery systems that can deliver drugs specifically to
tumor will produce improved treatment outcomes. Exosomes have a natural ability
to carry functional biomolecules, such as small RNAs, DNAs, and proteins, in
their lumen. This property makes exosomes attractive for use in drug delivery and
molecular diagnosis. Moreover, exosomes can be attached to nanoparticles and used
for high precision imaging. Exosomes are now considered an important component in
liquid biopsy assessments, which are useful for detecting cancers, including lung
cancer. Several studies are currently underway to develop methods of exploiting
exosomes for use as efficient drug delivery vehicles and to develop novel
diagnostic modalities. This chapter summarizes the current status of exosome
studies with regard to their use as theranostics in lung cancer. Examples from
other cancers have also been cited to illustrate the extensive applicability of
exosomes to therapy and diagnosis.
PMID- 29941102
TI - Thermosensitive Liposomes for Image-Guided Drug Delivery.
AB - Liposomes have been employed as cancer therapy clinically since the 1990s, with
the primary benefit of reduced toxicity but no appreciable efficacy improvement.
Thermosensitive liposomes (TSLs) are specifically formulated such that they
release the encapsulated drug when exposed to hyperthermic temperatures in the
fever range (~40-42 degrees C) and have been investigated as cancer therapy for
several decades, with first clinical trials initiated in the last decade.
Combined with localized hyperthermia, TSLs allow precise drug delivery to a
targeted region. Typically, the targeted tissue is exposed to localized
hyperthermia facilitated by an image-guided hyperthermia device. Thus, TSLs
enable image-guided drug delivery where drug is delivered to a tissue region
identified by medical imaging. Recent TSL formulations are based on the more
recent paradigm of intravascular triggered release, where drug is released
rapidly (within seconds) while TSLs pass through the vasculature of the heated
tissue region. The drug released within the blood then extravasates and is taken
up by cancer cells. These TSLs enable up to 20-30 times higher tumor drug uptake
compared to infusion of unencapsulated drug, and the dose locally delivered to
the heated region can be modulated based on heating duration. This chapter
reviews various TSL formulations, the different anticancer agents that have been
encapsulated, as well as targeted cancer types. Further, the various hyperthermia
devices that have been used for image-guided hyperthermia are reviewed, focusing
on those that have been employed in human patients.
PMID- 29941103
TI - Supramolecular Analytical Chemistry in Cancer Research.
AB - Supramolecular interactions, such as those observed between antibodies and
antigens, have been employed in developing analytical methods for several
decades. One major area of interest concerns cancer research, where intricate
supramolecular designs have emerged to tackle difficult analytes in complex tumor
systems. Our increasing knowledge toward supramolecular systems have elicited
profound interest in creating more efficient analytical approaches, evidenced by
the ever-growing body of literature in the field. Some of the novel tools have
indeed facilitated our understanding of cancer biology, through providing
previously inaccessible information. In this review, we describe common
strategies of developing supramolecular analytical methods and their
implementations in cancer research. We provide an overview for each of the
approaches and discuss representative examples in recent literature.
PMID- 29941104
TI - Gold Nanoparticles for the Delivery of Cancer Therapeutics.
AB - Gold nanoparticles (Au NPs) are very attractive and versatile nanoparticles since
they have a remarkable capacity to absorb and scatter light, convert optical
energy into heat via nonradiative electron relaxation dynamics, and surface
chemistries that can be capitalized upon so that the nanoparticles act as drug
carriers. Au NPs have excellent stability and biocompatibility, tailorable shapes
and sizes, an easily functionalized surface, high drug-loading capacity, and low
toxicity. The properties of Au NPs can be leveraged to develop more precisely
targeted and effective cancer therapeutics. Au NPs have been used to target
delivery of chemotherapeutic agents, complement radiation and thermal therapy,
and enhance contrast for in vivo imaging of the tumor in a variety of cancer
types and diseased organs.
PMID- 29941105
TI - Single-Cell Proteomics for Cancer Immunotherapy.
AB - Cancer immunotherapy fights against cancer by modulating the immune response and
is delivering encouraging results in clinical treatments. However, it is
challenging to achieve durable response in all cancer patients during treatment
due to the diversity and dynamic nature of immune system as well as inter- and
intratumor heterogeneity. A comprehensive assessment of system immunity and tumor
microenvironment is crucial for effective and safe cancer therapy, which can
potentially be resolved by single-cell proteomic analysis. Single-cell proteomic
technologies enable system-wide profiling of protein levels in a number of single
cells within the immune system and tumor microenvironment, and thereby provide
direct assessment of the functional state of the immune cells and tumor-immune
interaction that could be used to evaluate efficacy of immunotherapy and to
improve clinical outcome. In this chapter, we summarized current single-cell
proteomic technologies and their applications in cancer immunotherapy.
PMID- 29941106
TI - Nanotechnology Approaches to Improving Cancer Immunotherapy.
AB - Cancer immunotherapy is a powerful, growing treatment approach to cancer that can
be combined with chemotherapy, radiotherapy, and oncosurgery. Modulating the
immune system to enhance anticancer response by several strategies has yielded
improved cancer survival. Despite this progress, the success rate for
immunotherapy has been below expectations due to unpredictable efficacy and off
target side effects from systemic dosing. Nanotechnology offers numerous
different materials and targeting properties to overcome many of these challenges
in immunotherapy. In this chapter, we review current immunotherapy and its
challenges as well as the latest nanotechnology applications in cancer
immunotherapy.
PMID- 29941107
TI - Ultrasound Contrast Agents and Delivery Systems in Cancer Detection and Therapy.
AB - Ultrasound is the second most utilized imaging modality in the world because it
is widely accessible, robust, and safe. Aside from its extensive use in
diagnostic imaging, ultrasound has also been frequently utilized in therapeutic
applications. Particularly, when combined with appropriate delivery systems,
ultrasound provides a flexible platform for simultaneous real-time imaging and
triggered release, enabling precise, on-demand drug delivery to target sites.
This chapter will discuss the basics of ultrasound including its mechanism of
action and how it can be used to trigger the release of encapsulated drug either
through thermal or cavitation effects. Fundamentals of ultrasound contrast
agents, how they enhance ultrasound signals, and how they can be modified to
function as carriers for triggered and targeted release of drugs will also be
discussed.
PMID- 29941109
TI - Preface.
PMID- 29941108
TI - Dendronized Systems for the Delivery of Chemotherapeutics.
AB - This chapter reviews the use of dendronized systems as nanocarriers for the
delivery of chemotherapeutic drugs. Dendronized systems include dendrimers
prepared through convergent methods as well as other systems containing dendrons
(e.g., polymers, nanoparticles, liposomes). The preparation of such systems is
detailed, followed by the various conjugation techniques used for the transport
of chemotherapeutic drugs and their specific delivery to tumor cells. In
addition, the ability of dendronized systems to provide passive and active
targeting to tumors is discussed. The efficacy of drug delivery using dendronized
systems is also illustrated through specific examples of kinetic and biological
studies. Finally, the newest trends in conjugation of the most common
chemotherapeutics to dendronized systems are described. Overall, this chapter
highlights dendronized systems as a way to improve the therapeutic efficiency of
drugs for the treatment of cancer. All the recent developments in areas, such as
biodegradable dendrimers, modifications to enhance biocompatibility, selectively
cleavable drug conjugations, ligand-mediated targeting, and the potential for
multifunctional properties, show promises for future advances in cancer therapy.
PMID- 29941110
TI - Comparative Expression of CD34, Intercellular Adhesion Molecule-1, and Podoplanin
and the Presence of Mast Cells in Periapical Granulomas, Cysts, and Residual
Cysts.
AB - INTRODUCTION: The aim of the present study was to compare the immunoexpression of
CD34, intercellular adhesion molecule-1 (ICAM-1), and podoplanin and the presence
of mast cells with clinical, demographic, radiologic, and histologic features
from periapical granulomas, periapical cysts, and residual cysts. METHODS: Thirty
one lesions (5 granulomas, 15 periapical cysts, and 11 residual cysts) were
selected. Histologic sections in silanized slides were used for the
immunohistochemical reactions. The analysis of the images was performed by using
an optical microscope, and data were analyzed with 5% significance (P < .05).
RESULTS: Cysts presented atrophic and hyperplastic epithelium in 11 cases (35.5%)
and 15 cases (48.8%), respectively (P > .05). The intensity of the inflammatory
infiltrate was similar when comparing the 3 groups (P > .05). CD34 and podoplanin
expression and the presence of mast cells were similar when comparing the 3
groups; ICAM-1 expression was more intense in granulomas than cysts (P < .05).
There were no statistically significant differences associated with the
expression of the evaluated markers according to the intensity of the
inflammatory infiltrate. CONCLUSIONS: There were no differences in the expression
of CD34 and podoplanin and in the presence of mast cells when the 3 groups were
compared. ICAM-1 expression was more common in periapical granulomas.
PMID- 29941112
TI - Listing of the Plenary, Oral and Poster Presentations of the Abstracts of the
2018 American Brachytherapy Society Annual Meeting, June 7-9, 2018.
PMID- 29941111
TI - Guided Endodontic Access of Calcified Anterior Teeth.
AB - Pulp canal calcification is characterized by the deposition of calcified tissue
along the canal walls. As a result, the root canal space can become partially or
completely obliterated. Recently, "guided endodontics" has been reported as an
alternative solution in cases of partial or completed canal obliteration.
Although this technique can enhance minimally invasive access to the calcified
canal, it has been shown that the incisal surfaces are often removed during the
access of anterior teeth. This report describes 2 cases of guided endodontics
using conventional palatal access in calcified anterior teeth and discusses the
applicability of this approach in cases of pulp canal calcification with apical
periodontitis and acute symptoms. The method demonstrated high reliability and
permitted proper root canal disinfection expeditiously, without the unnecessary
removal of enamel and dentin in the incisal surface.
PMID- 29941113
TI - Discussion.
PMID- 29941114
TI - Discussion.
PMID- 29941116
TI - Discussion.
PMID- 29941115
TI - Discussion.
PMID- 29941117
TI - Discussion.
PMID- 29941118
TI - Discussion.
PMID- 29941119
TI - Resident Well-Being Programs: In reply to De Oliveira.
PMID- 29941121
TI - July 2018 Featured Articles, Volume 227.
PMID- 29941120
TI - Temporal Biases in the Evaluation of Resident Well-Being Programs?
PMID- 29941122
TI - Discussion.
PMID- 29941123
TI - Discussion.
PMID- 29941125
TI - Discussion.
PMID- 29941124
TI - Discussion.
PMID- 29941126
TI - Discussion.
PMID- 29941128
TI - Discussion.
PMID- 29941127
TI - Discussion.
PMID- 29941129
TI - Discussion.
PMID- 29941130
TI - Stand-alone cognitive behavioural therapy is not in clinical equipoise with
antipsychotic treatment - Author's reply.
PMID- 29941131
TI - Stand-alone cognitive behavioural therapy is not in clinical equipoise with
antipsychotic treatment.
PMID- 29941132
TI - Medication accessibility after diagnosis of ADHD in Croatia.
PMID- 29941133
TI - Medication accessibility after diagnosis of ADHD in Croatia - Authors' reply.
PMID- 29941134
TI - Empirical support for the psychoanalytic concepts.
PMID- 29941135
TI - Countering the prevailing narrative about the causes of the US opioid crisis.
PMID- 29941136
TI - Empirical support for the psychoanalytic concepts - Author's reply.
PMID- 29941138
TI - Michael Breakspear: using imaging to unravel psychiatric mysteries.
PMID- 29941139
TI - Self-help robots drive blues away.
PMID- 29941140
TI - Fly by night: I Am Not a Witch.
PMID- 29941141
TI - Chalk and cheese 2.0.
PMID- 29941142
TI - Decriminalization of Attempted Suicide across Asia- It Matters!
PMID- 29941143
TI - Editor's Perspectives - July 2018.
PMID- 29941144
TI - Spectral and molecular modeling investigations of supramolecular complexes of
mefenamic acid and aceclofenac with alpha- and beta-cyclodextrin.
AB - Inclusion complexes of mefenamic acid (MFA) and aceclofenac (ALF) with alpha- and
beta-cyclodextrins (CDs) in aqueous medium were investigated by absorption,
fluorescence, time-resolved fluorescence methods. The solid inclusion complexes
between drugs and CDs were characterized by SEM, TEM, FT-IR, 1H NMR, DSC and
powder XRD techniques. Spectral studies indicated that both CDs form 1:1
inclusion complex with MFA and ALF. The experimental results revealed that the
inclusion process is a spontaneous process. Time-resolved fluorescence studies
suggested that ALF exhibited biexponential decay in aqueous and triexponential
decay in CD whereas significant enhancement of lifetime of decay components of
MFA was observed. Morphologies of drug-CD complexes observed by TEM demonstrate
that self-aggregates of MFA/alpha-CD, ALF/alpha-CD and ALF/beta-CD were nano
sized particles while vesicles were observed for MFA/beta-CD. A spatial
arrangement of inclusion complex is proposed based on 1H NMR and PM3 results.
Investigations of thermodynamic and electronic properties confirmed the stability
of the inclusion complex.
PMID- 29941145
TI - The Class II Histone Deacetylase Hypothesis of Addiction.
PMID- 29941146
TI - Control of Cocaine Relapse: Lost in Translation.
PMID- 29941147
TI - Any Way You Splice It: New Molecular Mechanisms of Cocaine-Induced Alternative
Gene Expression.
PMID- 29941148
TI - The Electrochemical Brain: Lessons From The Bell Jar and Interventional
Psychiatry.
PMID- 29941149
TI - Influence of hospital volume on outcomes for patients with heart failure:
Evidence from a Canadian national cohort study.
AB - Although the Get with the Guidelines-Heart Failure (GWTG-HF) group recently
reported no association between hospital volume and 30-day outcomes in their
registry, GWTG-HF hospitals are self-selected and tend to be higher-volume
hospitals with active quality improvement departments. Thus, we explored the
volume-outcome relationship for HF in an unselected population-based cohort of
241,533 adults admitted with HF as the most responsible diagnosis to any of 591
acute care institutions in Canada-none participate in GWTG-HF. We found inverse
associations between volume and in-patient mortality (11.3% in low-volume
hospitals compared to 9.0% in high-volume hospitals, adjusted odds ratio 0.90
[0.80-1.00]) and 30-day readmission rates (19.3% in low-volume hospitals versus
17.3% in high-volume hospitals, adjusted odds ratio 0.91 [0.85-0.97]).
PMID- 29941150
TI - Multistage implantology-orthodontic-prosthetic treatment: A case report.
AB - BACKGROUND AND OVERVIEW: Patients increasingly expect esthetic and comfortable
fixed restorations on implants, are aware how important it is to maintain healthy
tooth tissue, and draw attention to the final result of treatment. CASE
DESCRIPTION: In this case report, the authors describe implantology-orthodontic
prosthetic treatment provided on a patient who reported symptoms of head, back,
and neck pain and had an impaired prosthetic plane, lack of space for prosthetic
crowns after the introduction of the implants and no good treatment plan, and
broken tooth roots of the mandibular anterior teeth. In addition, the patient
wanted to correct the shape and color of the rest of her teeth. The authors
present the different stages of the implantology-orthodontic-prosthetic treatment
and the final result after treatment. The patient was satisfied with the achieved
results of the treatment in terms of functionality and esthetics. She felt a
significant reduction in pain in the temporal, masseter, and sternocleidomastoid
muscles. The clenching of teeth at night decreased, and she began to sleep
better. Her well-being improved. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Before
the beginning of the treatment, dentists should make an accurate diagnosis and
determine if patients qualify for the treatment and the appropriate materials are
selected. Achieving the desired functional and esthetic effect often requires
cooperation with physicians in various specialties and multistage treatment.
PMID- 29941151
TI - The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral
Solution): Results of a Single-dose, Two-period Crossover Study.
AB - PURPOSE: Fenfluramine is being developed as a low-dose adjunctive treatment for
seizures in patients with Dravet syndrome and other epileptic encephalopathies,
including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive
multiple antiepileptic drugs, making it challenging for caregivers to track
correct administration times. The present Phase I study was conducted to
determine the effect of food on the pharmacokinetic properties of fenfluramine.
METHODS: Healthy nonsmoking subjects aged 18 to 50 years were enrolled in an open
label, crossover, Phase I pharmacokinetic and safety profile study and received 2
single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1
after a 10-hour overnight fast and the other 30 minutes after the start of
consumption of a high-fat breakfast, in a randomly assigned order. A washout
period of at least 9 days separated the 2 treatment periods. Venous blood samples
were taken before each dose and periodically for 72 hours after each dose for
determination of concentrations of fenfluramine and its active metabolite
norfenfluramine. Plasma pharmacokinetic parameters were estimated for each
subject by noncompartmental analysis. FINDINGS: In the 13 subjects completing
both treatment periods, food had no effect on the rate or extent of absorption
and bioavailability of fenfluramine as assessed by fed vs fasted adjusted
geometric mean observed plasma Cmax (59.1 vs 56.7 ng/mL; NS) and AUC0-infinity
(1640 vs 1600 ng . h/mL; NS). Additionally, there was no impact of food on
systemic exposure of norfenfluramine. Seven subjects reported at least 1
treatment-emergent adverse event; all treatment-emergent adverse events were mild
in severity. IMPLICATIONS: The bioequivalence and tolerability of single 0.8
mg/kg oral doses of ZX008 in the fed and fasted states support ZX008
administration without regard to meals.
PMID- 29941152
TI - Perivascular signals alter global gene expression profile of glioblastoma and
response to temozolomide in a gelatin hydrogel.
AB - Glioblastoma (GBM) is the most common primary malignant brain tumor, with
patients exhibiting poor survival (median survival time: 15 months). Difficulties
in treating GBM include not only the inability to resect the diffusively-invading
tumor cells, but also therapeutic resistance. The perivascular niche (PVN) within
the GBM tumor microenvironment contributes significantly to tumor cell invasion,
cancer stem cell maintenance, and has been shown to protect tumor cells from
radiation and chemotherapy. In this study, we examine how the inclusion of non
tumor cells in culture with tumor cells within a hydrogel impacts the overall
gene expression profile of an in vitro artificial perivascular niche (PVN)
comprised of endothelial and stromal cells directly cultured with GBM tumor cells
within a methacrylamide-functionalized gelatin hydrogel. Using RNA-seq, we
demonstrate that genes related to angiogenesis and extracellular matrix
remodeling are upregulated in the PVN model compared to hydrogels containing only
tumor or perivascular niche cells, while downregulated genes are related to cell
cycle and DNA damage repair. Signaling pathways and genes commonly implicated in
GBM malignancy, such as MGMT, EGFR, PI3K-Akt signaling, and Ras/MAPK signaling
are also upregulated in the PVN model. We describe the kinetics of gene
expression within the PVN hydrogels over a course of 14 days, observing the
patterns associated with tumor cell-mediated endothelial network co-option and
regression. We finally examine the effect of temozolomide, a frontline
chemotherapy used clinically against GBM, on the PVN culture. Notably, the PVN
model is less responsive to TMZ compared to hydrogels containing only tumor
cells. Overall, these results demonstrate that inclusion of cellular and matrix
associated elements of the PVN within an in vitro model of GBM allows for the
development of gene expression patterns and therapeutic response relevant to GBM.
PMID- 29941153
TI - [Risk of conjunctivitis associated with dupilumab (Dupixent(r))].
PMID- 29941154
TI - Building up marine biodiversity loss: Artificial substrates hold lower number and
abundance of low occupancy benthic and sessile species.
AB - Ocean sprawl is replacing natural substrates with artificial alternatives. We
hypothesized that, after submersion, high occupancy, high mobility species
colonize artificial substrates faster than low occupancy, low mobility species, a
biodiversity divergence that will slowly fade out with time. Using quantitative
visual census of species in 10 artificial and their adjacent natural substrates,
we tested for the existence and temporal evolution of this divergence. Assigning
species to one of three occupancy and one of three mobility categories, we found
that artificial substrates increased the performance of high mobility, high
occupancy species while decreased the performance of low occupancy species with
medium and low mobility. This biodiversity divergence remained unchanged over the
50-year underwater timespan of the artificial substrates investigated. Our
results suggest that proliferation of artificial substrates is building up a
biodiversity loss driven by the least conspicuous and uncommon benthic and
sessile species that is undermining coastal marine biodiversity.
PMID- 29941155
TI - The Unmet Promise of a Miracle Drug for Alzheimer's Disease: Implications for
Practice, Policy, and Research.
PMID- 29941156
TI - Antipsychotic Deprescription for Older Adults in Long-term Care: The HALT Study.
AB - OBJECTIVES: Despite limited efficacy and significant safety concerns,
antipsychotic medications are frequently used to treat behavioral and
psychological symptoms of dementia (BPSD) in long-term residential care. This
study evaluates the sustained reduction of antipsychotic use for BPSD through a
deprescribing intervention and education of health care professionals. DESIGN:
Repeated-measures, longitudinal, single-arm study. SETTING: Long-term residential
care of older adults. PARTICIPANTS: Nursing staff from 23 nursing homes recruited
139 residents taking regular antipsychotic medication for >=3 months, without
primary psychotic illness, such as schizophrenia or bipolar disorder, or severe
BPSD. INTERVENTION: An antipsychotic deprescribing protocol was established.
Education of general practitioners, pharmacists, and residential care nurses
focused on nonpharmacological prevention and management of BPSD. MEASUREMENTS:
The primary outcome was antipsychotic use over 12-month follow-up; secondary
outcomes were BPSD (Neuropsychiatric Inventory, Cohen-Mansfield Agitation
Inventory, and social withdrawal) and adverse outcomes (falls, hospitalizations,
and cognitive decline). RESULTS: The number of older adults on regular
antipsychotics over 12 months reduced by 81.7% (95% confidence interval: 72.4
89.0). Withdrawal was not accompanied by drug substitution or a significant
increase in pro-re-nata antipsychotic or benzodiazepine administration. There was
no change in BPSD or in adverse outcomes. CONCLUSION: In a selected sample of
older adults living in long-term residential care, sustained reduction in regular
antipsychotic use is feasible without an increase of BPSD.
PMID- 29941157
TI - [Identification and antibiotic susceptibility of viridans group streptococci
isolates recovered from patients hospitalized at a teaching hospital in Buenos
Aires City].
AB - Members of the viridans group streptococci (VGS) are the cause of local and
invasive infections. Due to the severity of these infections and taking into
account that reports regarding epidemiological aspects are scarce, the aims of
this work were the identification and the study of the antibiotic susceptibility
profiles of the isolates recovered from patients that were hospitalized in order
to find out about the resistance level and the epidemiology of infections in
which VGS are involved. A hundred and thirty two isolates identified as VGS were
isolated at Hospital de Clinicas "Jose de San Martin" during the period 2011
2015. The identification was performed by biochemical test and mass spectrometry
by Matrix Assisted Laser Desorption Ionization -Time of Flight Mass Spectrometry.
Streptococcus anginosus group was prevalent (42%) followed by Streptococcus mitis
group (33%). In the latter, isolates of Streptococcus pneumoniae were excluded.
All the VGS isolates were susceptible to ertapenem, meropenem, linezolid and
vancomycin; 25.8% were resistant (I+R) to penicillin, being prevalent in the S.
mitis group. Regarding ceftriaxone and cefepime 96.9% of the isolates were
susceptible. Only two isolates were resistant to levofloxacin, 27.2% to
tetracycline and it was not found high level resistance to gentamycin (MIC range
0.5-32MUg/ml). Resistance to erythromycin was 17.4% with no significant
difference between M and MLS phenotypes. The most active antibiotics were in
addition to ceftriaxone and cefepime, vancomycin, ertapenem, meropenem and
linezolid. These results highlight the importance of the continuous surveillance
of the infections caused by VGS in order to predict a correct antibiotic therapy.
PMID- 29941158
TI - Dietary meat and protection against sarcopenia.
AB - Sarcopenia describes the age-related loss of skeletal muscle mass and associated
muscle weakness. Sarcopenia is a major global health problem given that the
number and proportion of older people in the population is escalating worldwide
and represent the fastest growing segment of society. The loss of muscle mass
compromises physical capacity, increases susceptibility to falls, and impacts on
an individual's functional independence and quality of life. Tackling sarcopenia
sensibly and effectively will identify strategies that will enable older adults
to age well and age productively. The underlying causes of sarcopenia are complex
and multifactorial and will likely require combinatorial therapies to address its
symptoms. Nutrition, particularly protein intake, is a more easily modifiable
factor, especially when combined with structured (resistance) exercise programs.
The relative success of protein feeding strategies for sarcopenia, is limited by
a so-called anabolic resistance in older people. Meat contains essential amino
acids and nutritive compounds of high quality, and even a moderate intake can
increase muscle protein synthesis in older men and women. However, health risks
have been identified with the consumption of different meats, with high intake of
processed meats increasing the risk for cardiovascular disease and different
cancers. Risks for fresh white and red meat are considerably less and modest
consumption is encouraged as part of a healthy eating plan for many older adults
to ensure adequate protein intake. Other nutritive strategies of relevance for
sarcopenia involve fortifying the nutrient value of different meats. Studies on
muscle cells and animal models of muscle wasting, have identified the therapeutic
potential of the amino acid, glycine, to reduce inflammation, attenuate muscle
atrophy, and re-sensitize muscle to anabolic stimuli. Glycine supplementation or
feeding animal products with a high glycine content (e.g. gelatin), could
represent simple and effective nutritional strategies as part of a suite of
therapies to attenuate sarcopenia.
PMID- 29941159
TI - A systematic review on the quality of measurement techniques for the assessment
of burn wound depth or healing potential.
AB - PURPOSE: Reliable and valid assessment of burn wound depth or healing potential
is essential to treatment decision-making, to provide a prognosis, and to compare
studies evaluating different treatment modalities. The aim of this review was to
critically appraise, compare and summarize the quality of relevant measurement
properties of techniques that aim to assess burn wound depth or healing
potential. METHODS: A systematic literature search was performed using PubMed,
EMBASE and Cochrane Library. Two reviewers independently evaluated the
methodological quality of included articles using an adapted version of the
Consensus-based Standards for the selection of health Measurement INstruments
(COSMIN) checklist. A synthesis of evidence was performed to rate the measurement
properties for each technique and to draw an overall conclusion on quality of the
techniques. RESULTS: Thirty-six articles were included, evaluating various
techniques, classified as (1) laser Doppler techniques; (2) thermography or
thermal imaging; (3) other measurement techniques. Strong evidence was found for
adequate construct validity of laser Doppler imaging (LDI). Moderate evidence was
found for adequate construct validity of thermography, videomicroscopy, and
spatial frequency domain imaging (SFDI). Only two studies reported on the
measurement property reliability. Furthermore, considerable variation was
observed among comparator instruments. CONCLUSIONS: Considering the evidence
available, it appears that LDI is currently the most favorable technique; thereby
assessing burn wound healing potential. Additional research is needed into
thermography, videomicroscopy, and SFDI to evaluate their full potential. Future
studies should focus on reliability and measurement error, and provide a precise
description of which construct is aimed to measure.
PMID- 29941160
TI - An update on Toxoplasma gondii infections in northern sea otters (Enhydra lutris
kenyoni) from Washington State, USA.
AB - Toxoplasmosis in marine mammals is epidemiologically and clinically important.
Toxoplasma gondii antibodies (by modified agglutination test, cut-off >=1:25)
were detected in serum of 65 of 70 (92.9%) northern sea otters (Enhydra lutris
kenyoni) from Washington State, USA. Brains and/or muscles of 44 sea otters were
bioassayed in mice (INF-gamma knock-out [KO], Swiss Webster outbred [SW]) and
viable T. gondii was isolated from 22 of 44 (50%); T. gondii strains were lethal
to KO mice but not SW mice. These T. gondii isolates were further propagated in
cell culture. Multi-locus PCR-RFLP genotyping of cell culture-derived tachyzoites
revealed four different genotypes among 22 isolates including ToxoDB PCR-RFLP
genotype #5 (14 isolates), #1 (three isolates), #3 (four isolates), and #167 (one
isolate). PCR-DNA sequencing based genotyping using polymorphic gene GRA6
revealed one of four different alleles. Among the 14 RFLP genotype #5 strains, 10
have GRA6 sequences that match with the Type A, one match with the Type X, two
strains did not generate sequence data, and one strain had double peaks at known
polymorphic sites indicating a mixed infection. The seven strains belong to
genotypes #1 and #3, all have identical sequences to T. gondii Type II reference
isolate ME49. Genotype #167 strain has identical sequence to Type I reference
strain. In summary, we observed high seroprevalence, and high rate of isolation
of T. gondii from northern sea otters and predominant genotype #5 that has been
previously reported a dominant and widespread strain among terrestrial wildlife
in North America. GRA6 sequence analysis of the genotype #5 isolates indicated
the dominance of Type A lineage in sea otters in Washington State.
PMID- 29941161
TI - Impact of Gastrostomy Placement on Nutritional Status, Physical Health, and
Parental Well-Being of Females with Rett Syndrome: A Longitudinal Study of an
Australian Population.
AB - OBJECTIVES: To evaluate how age-related trends in nutritional status, physical
health, and parental well-being in females with Rett syndrome may be related to
gastrostomy placement and to examine the impact of the procedure on mortality.
STUDY DESIGN: We included 323 females from the Australian Rett Syndrome Study and
analyzed their demographic, genetic, and child and parental health data collected
from over 6 waves of follow-up questionnaire between 2000 and 2011. We used mixed
effects models to estimate the association between repeated measures of outcomes
and age, gastrostomy placement and their interaction and Cox proportional hazards
regression models to estimate relative risks of mortality for individuals with
gastrostomy. RESULTS: Nearly one-third (30.3%) of the cases underwent gastrostomy
placement. Nutritional status based on weight, height, and body mass index (BMI)
improved over time, and BMI was greater in individuals with gastrostomy placement
than in those without (adjusted beta = 0.87, 95% CI 0.02-1.73). There was no
association between gastrostomy placement and individual's physical health
outcomes or parental physical and mental health, nor did the age trend of these
outcomes vary by gastrostomy insertion status. Nevertheless, among those at risk
of suboptimal weight, the all-cause mortality rate was greater in those who had
gastrostomy placement compared with those who had not (hazard ratio 4.07, 95% CI
1.96-8.45). CONCLUSION: Gastrostomy placement was associated with improvement in
BMI in females with Rett syndrome, but its long-term impact on individuals and
their families is unclear.
PMID- 29941162
TI - Corneal Ring Abscess after Cardiac Surgery.
PMID- 29941163
TI - Defining the breaking point: Benefits and pitfalls of modeling long-term
durability of a third-generation transcatheter valve in an era of short-term
data.
PMID- 29941164
TI - Effectively treating mitral annular calcification will require out of the box
techniques.
PMID- 29941165
TI - Robotic mitral valve surgery: Additive benefits without additive cost.
PMID- 29941166
TI - Innovative surgery: Who does it and who gets it?
PMID- 29941167
TI - Are 2 procedures really better than 1 for patients undergoing coronary artery
bypass graft procedure?
PMID- 29941168
TI - Study of mitochondrial function in placental insufficiency.
AB - INTRODUCTION: It has been suggested that mitochondria play a crucial role in
sustaining pregnancy and foetal growth. The aim of the study was to assess the
influence of mitochondrial functions and genetics on placental insufficiency
diseases. METHODS: A total of 115 patients were recruited, subdivided into 74
placenta samples and 41 maternal blood samples: placental insufficiency diseases
including intra uterine growth restriction (IUGR) (n = 35), preeclampsia (PE) (n
= 13), IUGR associated to PE (PER) (n = 25); and controls (n = 42). Haplogroups
were determined for all patients. Eighty-six placenta samples were studied for
quantitative and qualitative analyses of mtDNA: IUGR (n = 25), PE (n = 1), PER (n
= 18) and controls (n = 42). Sixteen placenta samples were selected for
functional analysis: IUGR (n = 6), PER (n = 2) and controls (n = 8). RESULTS:
Mitochondrial DNA copy numbers and rearrangements and haplogroup distribution
were not significantly altered in the patient group. Enzyme activity and
expression of respiratory chain complexes were also comparable between both
groups. DISCUSSION: Our results do not argue in favour of a mitochondrial
involvement in placental insufficiency, suggesting that the glycolytic pathway
may represent a key energetic source in placental insufficiency diseases.
PMID- 29941170
TI - Classics revisited: C. J. van der Horst on pregnancy and menstruation in elephant
shrews.
AB - BACKGROUND: Menstruation occurs only in higher primates, some bats, the spiny
mouse and the elephant shrew. Our knowledge of the latter species is due to work
by C. J. van der Horst. FINDINGS: Changes in the uterine stroma are initially
similar in fertile and infertile cycles and are confined to a small area. In
pregnant animals, the presence of the conceptus causes further development to an
implantation chamber. In infertile cycles an outgrowth of highly glandular stroma
(a polyp) appears. With decline of the corpora lutea it is shed in a process
equivalent to menstruation. Van der Horst described the further development of
the placenta and a decidua pseudocapsularis in pregnant animals. In addition he
built a unique collection that has thrown light on embryonic development and
placentation in other South African mammals. CONCLUSIONS: The changes in
endometrial stromal cells during the menstrual cycle appear similar between
primates and the elephant shrew and deserve to be studied at the molecular level.
PMID- 29941169
TI - Oxidative stress induces p38MAPK-dependent senescence in the feto-maternal
interface cells.
AB - OBJECTIVE: This study tested the mechanism of the oxidative stress (OS)-induced
senescence pathway at the feto-maternal interface cells. METHODS: Primary amnion
mesenchymal cells (AMCs), chorion and decidual cells isolated from the placental
membranes of women at normal term (not in labor) were exposed to OS-inducing
cigarette smoke extract (CSE) for 48 h. Reactive oxygen species (ROS) was
measured using 2'7'-dichlorodihydrofluorescein. Western blot analysis determined
phosphorylated (P) p38MAPK and p53 expression. Senescence-associated beta
Galactosidase (SA-beta-Gal) and matrix metallopeptidase 9 (MMP9) histochemistry
were used to measure senescence and inflammation respectively. Cotreatment of
cells with the antioxidant, N-acetyl cysteine (NAC), or the p38MAPK inhibitor,
SB203580 (SB), verified the activation specificity. RESULTS: CSE increased ROS
production from AMCs, chorion cells, and decidual cells (P < 0.05) compared to
controls. Western blot analysis determined that CSE induced p38MAPK activation (P
< 0.05) and cotreatment with NAC inhibited ROS production and p38MAPK activation
(P < 0.05) in all cell types. CSE did not increase p53 phosphorylation in any of
the cells; however, AMCs showed constitutive P-p53 expression. CSE increased
senescence in AMCs and chorion cells compared to controls (P = 0.01 and P =
0.003, respectively); however, senescence was not observed in decidual cells.
Senescence was significantly reduced following cotreatment with SB and NAC (AMCs;
P = 0.01 and chorion; P = 0.009). CSE increased MMP9 in all cells that was
reduced by NAC. CONCLUSION: OS induced p38MAPK activation and inflammation in all
cell types that was associated with senescence in fetal cells but not in maternal
cells.
PMID- 29941171
TI - The association of the placental Hypoxia-inducible factor1-alpha polymorphisms
and HIF1-alpha mRNA expression with preeclampsia.
AB - INTRODUCTION: Evidence has confirmed that placental/fetal hypoxia plays a key
role in both endothelial cell dysfunction and PE pathogenesis. The aim of the
present study was to investigate whether maternal/placental hypoxia-inducible
factor1-alpha (HIF1-alpha) C1772T (rs11549465) and/or G1790A (rs11549467)
polymorphisms and HIF1-alpha mRNA expression are associated with PE development.
METHODS: The blood samples of 203 PE and 202 control women and the placenta of 86
PE and 84 control women were collected after delivery. The HIF1-alpha
polymorphisms were genotyped using PCR- RFLP method. The mRNA expression levels
were measured by Quantitative Real -Time PCR. RESULTS: The present study found no
association between maternal HIF1-alpha rs11549465 and rs11549467 and placental
rs11549467 polymorphisms and PE. However, the placental rs11549465 polymorphism
was associated with PE in the dominant model. The CT/GG combined genotypes and TG
haplotype of placental rs11549465 and rs11549467 polymorphisms were associated
with higher risk of PE. The HIF1-alpha mRNA expression was 3-fold higher in the
PE women. The rs11549465 TT genotype was associated with higher HIF1-alpha mRNA
expression in PE women and in total population and rs11549467 GA genotype was
associated with higher mRNA expression in total population. The relative mRNA
expression of HIF1-alpha gene was higher in presence of CC/GA, TT/GG and TT/GA
combined genotypes. CONCLUSION: This study found an association between placental
but not maternal HIF1-alpha rs11549465 polymorphism and PE in the dominant model.
The HIF1-alpha mRNA expression was higher in the placenta of PE women and was
associated with rs11549465 and rs11549467 polymorphisms.
PMID- 29941172
TI - Estrogen-related receptor gamma regulates expression of 17beta-hydroxysteroid
dehydrogenase type 1 in fetal growth restriction.
AB - INTRODUCTION: Estrogen-related receptor gamma (ERRgamma) and 17beta
hydroxysteroid dehydrogenase type 1 (HSD17B1) have important roles in cell
invasion and in the proliferation of many types of cancer cells. However, it
remains unknown whether ERRgamma and HSD17B1 contribute to abnormal placental
structure and dysfunction which characterize fetal growth restriction (FGR).
Therefore, the aim of this study was to investigate the expression profiles of
ERRgamma and HSD17B1 in placenta tissues affected by FGR and to examine a
possible molecular mechanism by which ERRgamma is able to regulate HSD17B1 during
development of FGR. METHODS: Placenta tissues were collected from women affected
by FGR (n = 28) and from women with appropriately gestational age (AGA) (n = 30).
Relative mRNA and protein levels of ERRgamma and HSD17B1 in both groups were
assessed by quantitative real-time PCR, immunohistochemistry, and Western blot
analyses. The effect of ERRgamma on trophoblast function and its associated
mechanistic details were studied in the trophoblast cell line, HTR-8/SVneo, which
was transfected with small interfering RNA (siRNA) targeting ERRgamma. RESULTS:
Both mRNA and protein levels of ERRgamma and HSD17B1 were significantly lower in
FGR placentae (P < 0.05). When ERRgamma expression was knocked down in HTR
8/SVneo cells with siRNA, invasion and proliferation were inhibited. In addition,
HSD17B1 expression was significantly decreased. In dual luciferase reporter
assays, ERRgamma stimulated transcription of HSD17B1 by targeting the ERRgamma
response element within its 5'-flanking promoter region. DISCUSSION: Aberrant
ERRgamma expression may contribute to the pathogenesis of FGR by regulating the
transcriptional activity of HSD17B1.
PMID- 29941173
TI - Altered expression of p97/Valosin containing protein and impaired autophagy in
preeclamptic human placenta.
AB - INTRODUCTION: Autophagy increases in placenta-related obstetrical diseases such
as preeclampsia and intrauterine growth retardation but the regulation of
autophagy by ubiquitin proteasome pathway (UPP) proteins, p97/Valosin containing
protein (VCP) and ubiquitin (Ub) have not been previuosly studied in
preeclampsia. The objective of this study is to investigate the expression of UPP
(p97/VCP and Ub), autophagosomal (p62 and LC3) and autolysosomal proteins (Lamp1
and Lamp2) in the normal and preeclamptic human placentas and to explore the
regulatory mechanism of these proteins in autophagic pathway. MATERIAL AND
METHODS: Different portions of normal term placentas (n = 20) and preeclamptic
placentas (n = 10) were snap-frozen in liquid nitrogen for Western blotting and
coimmunoprecipitation and others were fixed-embedded in paraffin for
immunohistochemistry. Colocalization and coimmunoprecipitation experiments were
done for the detection of interaction between p97/VCP and autophagic proteins.
RESULTS: Compared with normal placentas, expression of p97/VCP was significantly
reduced; however accumulation of ubiquitinlated proteins were significantly
increased in preeclamptic placentas. The expression of autophagosomal proteins
(LC3-II and p62) were significantly increased and no significant alterations of
the expression of autolysosomal proteins were observed in preeclamptic placentas.
Additionally, p97/VCP was found to colocalized and interact with autophagosomal
and autolysosomal markers in normal and preeclamptic placentas. Autophagosome
maturation diminished and autophagosomes had decreased localization with
lysosomal markers in preeclamptic human placentas. CONCLUSION: Decreased
expression of p97/VCP and increased expression of Ub in preeclampsia might be
related to impaired autophagy and pathophysiology of preeclampsia. Therefore, our
study highlights an important potential relationship between p97/VCP and
autophagic proteins in preeclampsia.
PMID- 29941174
TI - Subclinical and clinical chorioamnionitis, fetal vasculitis, and risk for preterm
birth: A cohort study.
AB - OBJECTIVE: To evaluate the association between subclinical and clinical
chorioamnionitis and risk of preterm birth (PTB). METHODS: Demographic and
clinical characteristics were abstracted from medical records and placental
examinations performed (N = 1371 pregnancies including spontaneous and medically
indicated PTBs). Pregnancies were classified as having clinical chorioamnionitis
(with or without histologic chorioamnionitis), subclinical chorioamnionitis
(histologic, but not clinical, chorioamnionitis), or no chorioamnionitis;
pregnancies with histologic chorioamnionitis were further evaluated for fetal
vasculitis. Relative risks for PTB, early and late PTB, and PTB +/- premature
rupture of membranes (PROM) were adjusted for maternal characteristics. RESULTS:
Clinical (4.3%) and subclinical (24.5%) chorioamnionitis were not associated with
PTB overall. In pregnancies without clinical or subclinical chorioamnionitis, the
risk of PTB with PROM and early PTB was 2.2% and 8.6%, respectively. In
comparison, clinical chorioamnionitis was associated with an increased risk of
PTB with PROM (aRR: 3.42 (95%CI: 1.07, 10.98), whereas subclinical
chorioamnionitis was associated with increased risk of PTB with PROM (aRR: 3.92
(95% CI: 2.15, 7.12)) and early PTB (aRR: 1.77 (95% CI: 1.18, 2.64)). Histologic
chorioamnionitis with fetal vasculitis was associated with increased risk of PTB
with PROM (aRR: 7.44 (95% CI: 3.68, 15.05)) and early PTB (aRR: 2.94 (95% CI:
1.78, 4.87)), whereas histologic chorioamnionitis without fetal vasculitis was
associated with increased risk of PTB with PROM only (aRR: 2.64, 95% CI: 1.27,
5.50). CONCLUSIONS: Subclinical chorioamnionitis and histologic chorioamnionitis
with fetal vasculitis were associated with early PTB and PTB with PROM but not
with PTB overall, likely due to inclusion of indicated PTBs.
PMID- 29941175
TI - The newly established bovine endometrial gland cell line (BEGC) forms gland acini
in vitro and is only IFNtau-responsive (MAPK42/44 activation) after E2 and P4-pre
incubation.
AB - INTRODUCTION: Uterine glands (UG) are crucial for the establishment of ruminant
pregnancy and influenced (orchestrated manner) by estrogen (E2), progesterone
(P4) and interferon tau (IFNtau). In the study we established a bovine
endometrial glandular cell line (BGEC) and tested its functional reactivity
(signaling) to IFNtau. METHODS: BGEC was characterized by light microscopy (LM),
epithelial markers (ezrin, CK18) [immunofluorescence (IF)/immunohistochemistry
(IHC)] and ultrastructure (TEM/SEM) (apical microvilli). In vitro formation of
gland acini and transepithelial-electric-resistance (TEER) measurements (EVOM)
were done. The expression of mRNA-transcripts (RT-PCR) of steroid receptors (PR,
PGRMC1/2, ESR1/2) and the IFNtau-system (IFNAR1/2, IRF1, 2, 9) was checked. BEGC
was stimulated with IFNtau (10 ng/ml;1000 ng/ml) (15 min) after steroid pre
treatment [10 pg/ml E2 (two days)/20 ng/ml P4 (two days)]. Activation of
MAPK42/44;STAT1 was evaluated (densitometrical Western Blot). RESULTS: BGEC cells
expressed epithelial markers and possessed apical microvilli. High TEER-values
could be measured (2320-2620 ohm/cm2). The assembled BEGC acini (25 days) were
similar to UG in vivo (markers/ultrastructure). All transcripts (steroid
receptors/IFNtau-system) could be detected in BEGC (mRNA). MAPK42/44 were
significantly activated after E2/P4 pre-treatment and IFNtau stimulation (10
ng/ml) (p < 0.05), whilst 1000 ng/ml IFNtau did not activate MAPK42/44. Neither a
STAT1 (by IFNtau) nor an activation (MAPK42/44;STAT1) by IFNtau-only was
observed. DISCUSSION: BGEC retains its epithelial phenotype in culture and forms
gland acini in vitro thereby confirming its glandular character. Cells were only
reactive to (low) IFNtau concentrations when pre-treated with steroids thereby
closely resembling implantation physiology in vivo. BEGC can be used as a bovine
implantation model to study embryo-maternal communication during early pregnancy
in cattle.
PMID- 29941176
TI - Human placentophagy: Effects of dehydration and steaming on hormones, metals and
bacteria in placental tissue.
AB - INTRODUCTION: Human maternal placentophagy, the behavior of ingesting the own raw
or processed placenta postpartum, is a growing trend by women of western
societies. This study aims to identify the impact of dehydration and steaming on
hormone and trace element concentration as well as microbial contamination of
placental tissue. METHODS: A total of nine placentas have been processed: six
were studied for hormone and trace element concentrations; eight were studied for
microbial contamination. The concentrations of CRH, hPL, oxytocin and ACTH in
samples of raw, steamed dehydrated and raw dehydrated placental tissue were
detected using ELISA. A yeast bioassay was performed in order to detect estrogen
equivalent (EEQ) and gestagen equivalent (PEQ) active substances. Elements (As,
Cd, Fe, Pb, Se, Hg) were analyzed using ICP-MS. Isolated colonies from tissue and
placenta swab samples were identified using Vitek MS. RESULTS: Following mean
hormone concentrations were detected in raw placental tissue: CRH (177.88 ng/g),
hPL (17.99 mg/g), oxytocin (85.10 pg/g), ACTH (2.07 ng/g), estrogen equivalent
active substances (46.95 ng/g) and gestagen equivalent active substances (2.12
MUg/g). All hormones were sensitive to processing with a significant
concentration reduction through steaming and dehydration. Microorganisms mainly
from the vaginal flora were detected on placenta swab samples and samples from
raw, steamed, dehydrated and steamed dehydrated tissue and mostly disappeared
after dehydration. According to regulations of the European Union the
concentrations of potentially toxic elements (As, Cd, Hg, Pb) were below the
toxicity threshold for foodstuffs. CONCLUSION: The commonly used protocols for
preparation of placenta for its individual oral ingestion reduce hormone
concentrations and bacterial contamination.
PMID- 29941177
TI - Editorial overview: Cardiovascular and renal: Novel therapies in peripheral
artery disease.
PMID- 29941178
TI - The ORBITA Trial: What Does It Mean for Practice?
PMID- 29941179
TI - The Forgotten Art of Balloon Angioplasty.
PMID- 29941180
TI - Size Matters: Moving Toward a Slender Transradial Artery Approach.
PMID- 29941181
TI - Treatment Paradigm for Nasal Airway Obstruction.
AB - Nasal airway obstruction (NAO) is a common otolaryngic complaint with many
potential causes, frequently structural or inflammatory in nature. Patients
typically have multiple coexisting factors leading to symptoms. Good patient
outcomes require careful preoperative evaluation, including nasal endoscopy, to
accurately identify sources of obstruction and tailor intervention appropriately.
Common structural causes of NAO include inferior turbinate hypertrophy, nasal
septal deviation, and narrowing or collapse of the internal or external nasal
valves. The internal nasal valve has the narrowest cross-sectional area within
the nasal airway and is thus most sensitive to changes in dimension due to
anatomic variation or surgical intervention.
PMID- 29941182
TI - Anatomy and Physiology of Nasal Obstruction.
AB - Nasal obstruction is a common presenting symptom to clinicians and affects up to
one-third of the population. There are several factors that cause nasal
obstruction, including anatomic, physiologic, and pathophysiologic factors. The
anatomy and physiology of nasal obstruction is complicated and is influenced by
patency of nasal passages, mucociliary function, airflow receptors, autonomic
function, and degree of mucosal inflammation. Common anatomic causes include
internal nasal valve stenosis/collapse, septal deviation, and turbinate
hypertrophy. Common physiologic causes include sinonasal inflammatory disorders
and iatrogenic causes.
PMID- 29941187
TI - Yeast and Human Nuclear Pore Complexes: Not So Similar After All.
AB - Nucleoporin subunits that generate the nuclear pore complex (NPC) are highly
conserved in evolution. High-resolution structures of the NPC are available, but
the actual NPC composition in yeast has only been quantified recently. Two
studies reveal major differences between species, suggesting high flexibility in
NPC structures during evolution.
PMID- 29941188
TI - How Ralstonia solanacearum Exploits and Thrives in the Flowing Plant Xylem
Environment.
AB - The plant wilt pathogen Ralstonia solanacearum thrives in the water-transporting
xylem vessels of its host plants. Xylem is a relatively nutrient-poor, high-flow
environment but R. solanacearum succeeds there by tuning its own metabolism and
altering xylem sap biochemistry. Flow influences many traits that the bacterium
requires for pathogenesis. Most notably, a quorum sensing system mediates the
pathogen's major transition from a rapidly dividing early phase that voraciously
consumes diverse food sources and avidly adheres to plant surfaces to a slower
growing late phase that can use fewer nutrients but produces virulence factors
and disperses effectively. This review discusses recent findings about R.
solanacearum pathogenesis in the context of its flowing in planta niche, with
emphasis on R. solanacearum metabolism in plants.
PMID- 29941189
TI - Liposome-aided metabolic engineering of tumor surface immunogenicity.
AB - Approaches to increase tumor immunogenicity are of therapeutic potentials. We
herein reported the use of liposomes for covalent incorporation of neoantigen on
tumor surfaces with DNP-conjugated sialic acid (DNPSia). Relative to free DNPSia,
sugar-encapsulated biotinylated liposomes (DNPSia@LP@biotin) enables effective
cell surface expression of DNPSia on biotin receptor (BR)-expressing cells over
BR-free cells in vitro, and on tumor cell surfaces with high tumor-to-normal
tissue contrast in a mice model. These findings suggest the potentials of
targetable liposomes for modulating tumor surface immunity via metabolic
oligosaccharide engineering.
PMID- 29941190
TI - Recent progress in human telomere RNA structure and function.
AB - Human telomeric DNA is transcribed into telomeric RNA in cells. Telomeric RNA
performs the fundamental biological functions such as regulation and protection
of chromosome ends. This digest highlights the human telomere RNA G-quadruplex
structures, telomere RNA functions, G-quadruplex-binding small molecules, and
future prospects.
PMID- 29941191
TI - Canonical translation-modulating OFF-riboswitches with a single aptamer binding
to a small molecule that function in a higher eukaryotic cell-free expression
system.
AB - We have found that OFF-riboswitches that ligand-dependently downregulate the
canonical translation in a higher eukaryotic expression system (wheat germ
extract) can be easily created by inserting a single aptamer into the 5'
untranslated region (UTR) of mRNA, even if its ligand is as small as
theophylline. The key is the position of the inserted aptamer: the 5' end (+0
position) is much better than other positions for inhibiting canonical
translation with the aptamer-ligand complex. The data showed that ribosome
loading is suppressed by a rigid structure in the 5' end, and this suppression is
dependent on the structure's stability but not on its size. Although this
preference of aptamer insertion point contradicts the results in a lower
eukaryote, it accords with the fact that the 5'-end structural hindrance is more
effective for blocking the ribosome in higher eukaryotes. Therefore, the present
type of OFF-riboswitch would function in various higher eukaryotic expression
systems.
PMID- 29941192
TI - Iatrogenic pneumothorax during hypoglossal nerve stimulator implantation.
AB - Hypoglossal nerve stimulation is a promising new treatment for patients with
obstructive sleep apnea. In the initial Stimulation Therapy for Apnea Reduction
Trial, the overall rate of serious adverse events was <2% and no cases of
pneumothorax were reported. We present the case of an iatrogenic pneumothorax
during placement of the chest sensor lead between the intercostal muscles.
Following clinical and radiological evaluation, surgery was continued and the
patient was treated expectantly. In the following review, we discuss
pathophysiology, diagnosis, and expected outcomes. Surgeons placing hypoglossal
nerve stimulators should be aware of complications and prepared to manage a
pneumothorax.
PMID- 29941193
TI - Identification of PKMYT1 inhibitors by screening the GSK published protein kinase
inhibitor set I and II.
AB - As a member of the Wee-kinase family protein kinase PKMYT1 is involved in G2/M
checkpoint regulation of the cell cycle. Recently, a peptide microarray approach
led to the identification of a small peptide; EFS247-259 as substrate of PKMYT1,
which allowed for subsequent development of an activity assay. The developed
activity assay was used to characterize the PKMYT1 catalyzed phosphorylation of
EFS247-259. For the first time kinetic parameters for PKMYT1, namely Km, Km, ATP
and vmax were determined. The optimized assay was used to screen the published
protein kinase inhibitor sets (PKIS I and II), two sets of small molecule ATP
competitive kinase inhibitors reported by GlaxoSmithKline. We identified ten
inhibitors, providing different scaffolds. The inhibitors were further
characterized by using binding assay, activity and functional assay. In addition,
docking studies were carried out in order to rationalize the observed biological
activities. The derived results provide the basis for further chemical
optimization of PKMYT1 inhibitors and for further analysis of PKMYT1 as target
for anti-cancer therapy.
PMID- 29941194
TI - Corrigendum to "Exploration of multi-target potential of chromen-4-one based
compounds in Alzheimer's disease: Design, synthesis and biological evaluations"
[Bioorg. Med. Chem. 25 (2017) 6273-6285].
PMID- 29941195
TI - Cancer immunotherapy: Great expectations in the world of oncology but a cause for
kidney concern.
PMID- 29941196
TI - [Inhalational anesthesia maintenance with the Janus facial mask for transcatheter
aortic-valve replacement: a case series].
AB - BACKGROUND AND OBJECTIVES: Aortic stenosis is the most common type of heart valve
disease. Percutaneous aortic valve replacement has become the alternative for
patients considered at high risk for surgery. Controlled mechanical ventilation
with tracheal intubation has been the choice for this type of procedure, however
the use of noninvasive ventilation in cardiac patients has shown to be
beneficial. Janus is a novel full-face mask that allows application of
noninvasive ventilation support during anesthesia. Our main objective was to
evaluate the feasibility of transcatheter aortic valve replacement with prolonged
transesophageal echocardiographic monitoring under deep inhalational sedation
delivered through a new mask for noninvasive ventilation. METHODS: A case series
observational study that included five patients with critical aortic stenosis
that underwent inhalational anesthesia with sevoflurane for transcatheter aortic
valve replacement in a hybrid room of a teaching hospital. Standard monitors and
bispectral index were used, followed by inhalational induction and placement of
the Janus mask. Anesthesia was maintained with sevoflurane. Patients were
transferred to intensive care unit after the procedure. Complications related to
the mask use, transesofageal echocardiography accessibility and respiratory
implications to the patients were recorded. RESULTS: All procedures were
uneventful and no major complications were observed intraoperatively. One patient
presented CO2 retention (50mmHg) and sevoflurane leak around the central opening
of the mask, both without clinical significance. CONCLUSIONS: The use of
inhalational anesthesia with the facial mask Janus is a safe and efficient
alternative to general anesthesia with tracheal intubation for transcatheter
aortic valve replacement and can easily accommodate the use of transesophageal
echocardiography intraoperatively.
PMID- 29941197
TI - The effect of the frictional heat on retention and efficiency in thermostated or
insulated chromatographic columns packed with sub-2-MUm particles.
AB - The mass-transfer properties of a core-shell packing material with 1.6 MUm
particle diameter, and that of a fully porous packing material with 1.7 MUm
particle diameter were investigated and compared. The first absolute and the
second central moments of the peaks of the homologous series of alkylbenzenes,
over a wide range of mobile phase velocities were measured and used for the
calculation of the mass-transfer coefficients. For the evaluation of the band
broadening caused by the thermal dissimilarities, the measurements were carried
out under thermostated conditions and also at near adiabatic insulation of the
columns.
PMID- 29941198
TI - A micro gas chromatographic column with embedded elliptic cylindrical posts.
AB - In this paper, a novel embeded elliptic cylindrical posts (ECPs) with large
surface area and wide effective width, which could support more stationary phase
and decrease the pressure drop, is applied on the micro-fabricated gas
chromatographic (MUGC) column. Compared with MUGC column with cylindrical posts
(CPs), the surface area and effective width of MUGC column with ECPs are
increased by 29% and 30%. Separation experiments are performed under the same
head pressure at column inlet: in experiments of separating mixture 1, the column
efficiency of the MUGC column with ECPs for C9 has a 76% improvement, and the
separation resolution between C8 and C9 also has a 34% improvement; in
experiments of separating mixture 2, seven kinds of analytes can be identified by
the MUGC column with ECPs less than ten minutes, while, only six kinds can be
identified by the MUGC column with CPs in almost the same time. In detail, the
column efficiency of the MUGC column with ECPs for toluene has a 129%
improvement, and the separation resolution between benzene and toluene also has a
56.4% improvement. Hence, the MUGC column with the inner structures of ECPs is a
valid means to improve column efficiency and resolution in a lower pressure drop.
PMID- 29941199
TI - Virtual reality head-mounted display for endoscopically-assisted implant surgery.
PMID- 29941201
TI - Chronic granulomatous interstitial nephritis and urothelial metaplasia associated
with ritonavir-boosted atazanavir: a case study and literature review.
PMID- 29941202
TI - 53-Year-Old Man With Progressive Dyspnea and Orthopnea.
PMID- 29941200
TI - Targeted sequencing of burn scar-related squamous cell carcinomas identified
PIK3CA amplification.
PMID- 29941203
TI - Helminth-Bacterial Interactions: Cause and Consequence.
AB - Intestinal helminths, along with mutualistic microbes, have cohabited the
intestine of mammals throughout evolution. Interactions between helminths,
bacteria, and their mammalian hosts may shape not only host-helminth and host
microbiome interactions, but also the relationship between helminths and the
microbiome. This 'menage a trois' situation may not be completely balanced in
that it may favor either the host or the parasite, possibly at the cost of the
other partner. Similarly, helminths may favor the establishment of a particular
microbiome with either positive or negative consequences for the overall health
and well-being of the host. Recent studies indicate that infection with
intestinal helminths can and does impact the intestinal microbiome, with
important consequences for each partner in this tripartite relationship.
PMID- 29941204
TI - Challenged but not threatened: Managing health in advanced age.
AB - In this paper we reflect on discussions with people of advanced age in Aotearoa
New Zealand, and draw on theoretical frameworks of resilience and place in old
age, to explore insights about the ways older people maintain quality of life and
health. Twenty community-dwelling people of advanced age (85+) were recruited in
2015-16 from a large multidisciplinary longitudinal study of advanced age. These
twenty participated in interviews about health in advanced age, impact of
illnesses, interactions with clinicians, access to information, support for
managing health, and perceptions of primary care, medications, and other forms of
assistance. We use a positioning theory framework drawing on thematic and
narrative analysis to understand the dynamic ways people in advanced age position
themselves and the ways they age well through speech acts and storylines. People
in advanced age saw themselves as challenged, rather than threatened, by
adversities, and positioned themselves as able to draw on a lifetime of
experience and resourcefulness and collaborations with supporters to deal with
challenges. Key strategies include downplaying illness and resisting biomedical
discourses of complexity, positioning embodied selves as having agency, and
creative adaptation in the face of loss. People in advanced age exhibit
resilience, maintaining wellbeing, autonomy and good physical and mental quality
of life even while living with challenges such as functional decline and multi
morbidities. These findings have significance for supporters of older people,
emphasising the need to move away from a narrow focus on problems to working
together WITH people in advanced age to offer a more holistic approach that
encourages and enhances adaptation and flexibility, rather than rigid and
counterproductive coping patterns.
PMID- 29941205
TI - Classic Models for New Perspectives: Delving into Helminth-Microbiota-Immune
System Interactions.
AB - Whilst a wealth of data indicate that infections by gastrointestinal helminths
are accompanied by significant alterations in the composition of the vertebrate
gut flora, little is known of the immune-molecular mechanisms that regulate host
parasite-microbiota interactions. 'Traditional' experimental models of
gastrointestinal helminthiases, in which the role(s) of each of the components of
this triad can be tested, provide an opportunity to advance research in this
area. In this article, we propose the Echinostoma caproni-mouse system as a
potentially useful tool for studies of the role of the host gut microbiota in
preventing pathology and inducing parasite clearance via interleukin (IL)-25, an
epithelial-derived alarmin with key roles in antihelminth immunity and
maintenance of gut homeostasis.
PMID- 29941206
TI - [Immunotherapy in lung cancer: New concepts].
AB - Improvements in knowledge about the complexity of the tumor microenvironment have
paved the way for a revolution in lung cancer treatment with the emergence of
immune checkpoint inhibitors. The immune checkpoints negatively regulate immune
cells and lead to a dormant state: the immune cells are then unable to interact
effectively with their targets. The immune checkpoint inhibitors are monoclonal
antibodies that block immune checkpoints and permit reactivation of the immune
response against the tumor. Although immune checkpoint inhibitors are effective
as monotherapy, several other immune targets exist. The better understanding of
the involvement of these new targets in the immune response against tumors is
leading to the design of new compounds and new therapeutic approaches.
PMID- 29941207
TI - [Alcohol consumption and lung damage: Dangerous relationships].
AB - INTRODUCTION: Binge drinking and continued alcohol use in large amounts are
associated with many health problems but there are very few studies on the
effects of alcohol intake on the function of lung, the effects of ethanol on lung
diseases, and links between alcohol consumption and lung cancer. Therefore, our
knowledge of these interactions from pathophysiological, clinical and
epidemiological aspects is poor. BACKGROUND: Acute alcohol exposure stimulates
the beating of the cilia of mucociliary epithelium cells but the effects of
chronic ethanol over-exposure are different, with a progressive desensitization
of ciliary response: ethanol exposure reduces airway mucociliary clearance. As a
result this important innate primary defense mechanism, which protects the lungs
from the deleterious effects of different pollutants, allergens and pathogens, is
weakened. Chronic alcohol exposure alters the adaptative immune response to
pathogens (decreasing the phagocytic function of macrophages) and leads to an
inflammatory response (pro-inflammatory cytokines). Respiratory function is
impaired by alcohol misuse: asthma, chronic obstructive pulmonary disease, lung
infections, and the acute respiratory distress syndrome are more frequent and
severe. It is difficult to establish a causal link between alcohol and lung
cancer as the lung cancer risk is likely confounded by the effect of smoking.
Very few studies among never smokers have been conducted until now and the
results are not consistent: they are therefore necessary to confirm or refute
whether lung cancer is attributable to alcohol misuse. CONCLUSION: The pulmonary
effects of alcohol misuse are many but further investigations into the mechanism
by which alcohol might predispose to lung cancer are necessary.
PMID- 29941208
TI - The interaction of muscle moment arm, knee laxity, and torque in a multi-scale
musculoskeletal model of the lower limb.
AB - INTRODUCTION: Musculoskeletal modeling allows insight into the interaction of
muscle force and knee joint kinematics that cannot be measured in the laboratory.
However, musculoskeletal models of the lower extremity commonly use simplified
representations of the knee that may limit analyses of the interaction between
muscle forces and joint kinematics. The goal of this research was to demonstrate
how muscle forces alter knee kinematics and consequently muscle moment arms and
joint torque in a musculoskeletal model of the lower limb that includes a
deformable representation of the knee. METHODS: Two musculoskeletal models of the
lower limb including specimen-specific articular geometries and ligament
deformability at the knee were built in a finite element framework and calibrated
to match mean isometric torque data collected from 12 healthy subjects. Muscle
moment arms were compared between simulations of passive knee flexion and maximum
isometric knee extension and flexion. In addition, isometric torque results were
compared with predictions using simplified knee models in which the deformability
of the knee was removed and the kinematics at the joint were prescribed for all
degrees of freedom. RESULTS: Peak isometric torque estimated with a deformable
knee representation occurred between 45 degrees and 60 degrees in extension,
and 45 degrees in flexion. The maximum isometric flexion torques generated by
the models with deformable ligaments were 14.6% and 17.9% larger than those
generated by the models with prescribed kinematics; by contrast, the maximum
isometric extension torques generated by the models were similar. The change in
hamstrings moment arms during isometric flexion was greater than that of the
quadriceps during isometric extension (a mean RMS difference of 9.8 mm compared
to 2.9 mm, respectively). DISCUSSION: The large changes in the moment arms of the
hamstrings, when activated in a model with deformable ligaments, resulted in
changes to flexion torque. When simulating human motion, the inclusion of a
deformable joint in a multi-scale musculoskeletal finite element model of the
lower limb may preserve the realistic interaction of muscle force with knee
kinematics and torque.
PMID- 29941209
TI - Diffusion of antibiotics in intervertebral disc.
AB - Delivering charged antibiotics to the intervertebral disc is challenging because
of the avascular, negatively charged extracellular matrix (ECM) of the tissue.
The purpose of this study was to measure the apparent diffusion coefficient of
two clinically relevant, charged antibiotics, vancomycin (positively charged) and
oxacillin (negatively charged) in IVD. A one-dimensional steady state diffusion
experiment was employed to measure the apparent diffusion coefficient of the two
antibiotics in bovine coccygeal annulus fibrosus (AF) tissue. The averaged
apparent diffusion coefficient for vancomycin under 20% compressive strain was
7.94 +/- 2.00 * 10-12 m2/s (n = 10), while that of oxacillin was 2.26 +/- 0.68 *
10-10 m2/s (n = 10). A student's t-test showed that the diffusivity of vancomycin
was significantly lower than that of oxacillin. This finding may be attributed to
two factors: solute size and possible binding effects. Vancomycin is
approximately 3 times larger in molecular weight than oxacillin, meaning that
steric hindrance likely plays a role in the slower transport. Reversible binding
between positive vancomycin and the negative ECM could also slow down the rate of
diffusion. Therefore, more investigation is necessary to determine the specific
relationship between net charge on antibiotic and diffusion coefficients in IVD.
This study provides essential quantitative information regarding the transport
rates of antibiotics in the IVD, which is critical in using computational
modeling to design effective strategies to treat disc infection.
PMID- 29941210
TI - Reply to "Depression among patients with epilepsy - A diagnostic approach".
PMID- 29941211
TI - Nonlesional late-onset epilepsy: Semiology, EEG, cerebrospinal fluid, and seizure
outcome characteristics.
AB - INTRODUCTION: Incidence and prevalence of epilepsy increase with advancing age.
Although the majority of late-onset epilepsies are of lesional origin, a
considerable proportion of patients present with unknown etiology. The aim of
this study was to evaluate the semiological, electroencephalographic (EEG), and
cerebrospinal fluid (CSF) characteristics as well as the 12-month seizure outcome
in a cohort of patients with nonlesional late-onset epilepsy (>=55 years).
METHOD: A total of 54 patients with newly diagnosed nonlesional late-onset
epilepsy (NLLOE) were retrospectively evaluated for seizure type using the most
recent International League Against Epilepsy (ILAE) classification of seizure
types, EEG characteristics, and CSF profile and followed-up for at least 12
months after epilepsy onset. Results were compared with a gender-matched control
group of 58 patients with nonlesional early-onset epilepsy (NLEOE). RESULTS: The
predominant seizure types in NLLOE were focal to bilateral tonic-clonic seizures
(30%) as well as focal onset impaired awareness motor seizures (IAMS) (22%) and
focal onset impaired awareness nonmotor seizures (IANMS) (22%). The predominant
seizure types in NLEOE were focal to bilateral tonic-clonic seizures (43%) as
well as focal onset aware nonmotor seizures (ANMS) (31%) and IAMS (31%). Focal
onset impaired awareness nonmotor seizures were found to be more characteristic
in patients with NLLOE (p = 0.019; alpha < 0.05; NLLOE: 22.2% vs. NLEOE: 8.6%).
Electroencephalography revealed no significant differences between groups. Of
interest, three patients with NLLOE (8%) presented with oligoclonal bands (OCB)
in CSF albeit absence of antineuronal antibodies. Seizure-free rate was 70%.
Adverse effects from medication leading to antiepileptic drug (AED) change were
reported in 12 patients (22%), valproate was the best tolerated AED in patients
with NLLOE [adverse effects in 9%, compared with 12% (gabapentin) and 26%
(levetiracetam)]. CONCLUSIONS: Using the most recent classification system,
different patterns of semiological characteristics were identified: NLLOE more
frequently present with IANMS, whereas patients with NLEOE rather have ANMS.
Oligoclonal bands were only detected in patients with NLLOE, indicating that
careful exclusion of autoimmune encephalitis in this patient group is warranted.
Our findings may help to more accurately identify and characterize patients with
NLLOE to improve targeted diagnostics and adequate treatment in this challenging
group of patients.
PMID- 29941212
TI - The role of mTOR inhibitors in preventing epileptogenesis in patients with TSC:
Current evidence and future perspectives.
AB - Tuberous sclerosis complex (TSC) is one of the most common genetic causes of
epilepsy. Mutations in the TSC1 or TSC2 genes lead to the dysregulation of the
mechanistic target of rapamycin (mTOR) pathway. This mTOR pathway hyperactivation
is associated with several processes resulting in epileptic conditions. The
occurrence of seizures and their treatment outcomes seem to play a crucial role
in cognitive and behavioral developments in patients with TSC. Mechanistic target
of rapamycin inhibitors have been proven to be effective in epilepsy treatment in
individuals with TSC. Specifically, because of their disease-modifying mechanism
of action, they have the capability to prevent epileptogenesis in patients with
TSC. This article will provide an overview of the current evidence of and
delineate future perspectives for mTOR inhibitors and their role in preventing
epileptogenesis.
PMID- 29941213
TI - Natriuretic peptide based therapeutics for heart failure: Cenderitide: A novel
first-in-class designer natriuretic peptide.
AB - Cenderitide is a novel designer natriuretic peptide (NP) composed of C-type
natriuretic peptide (CNP) fused to the C-terminus of Dendroaspis natriuretic
peptide (DNP). Cenderitide was engineered to co-activate the two NP receptors,
particulate guanylyl cyclase (pGC)-A and pGC-B. The rationale for its design was
to achieve the renal-enhancing and anti-fibrotic properties of dual receptor
activation, but without clinically significant hypotension. Here, we review the
biology of the NPs and the rationale for their use in heart failure. Most
importantly, we present the key studies related to the discovery of Cenderitide.
Finally, we review the key clinical studies that have advanced this first-in
class dual NP receptor activator for heart failure.
PMID- 29941214
TI - Inactivation of Planktonic Escherichia coli by Focused 1-MHz Ultrasound Pulses
with Shocks: Efficacy and Kinetics Upon Volume Scale-Up.
AB - This study addresses inactivation of E. coli in either 5- or 10-mL volumes, which
were 50- to 100-fold greater than used in an earlier study (Brayman et al. 2017).
Cells were treated with 1-MHz pulsed high-intensity focused ultrasound (10
cycles, 2-kHz repetition frequency, +65/-12.8 MPa focal pressures). The surviving
fraction was assessed by coliform assay, and inactivation demonstrated
curvilinear kinetics. The reduction of surviving fraction to 50% required 2.5 or
6 min in 5- or 10-mL samples, respectively. Exposure of 5 mL for 20 min reduced
the surviving fraction to ~1%; a similar exposure of 10-mL samples reduced the
surviving fraction to ~10%. Surviving cells from 5-min exposures appeared normal
under light microscopy, with minimal debris; after 20 min, debris dominated.
Transmission electron microscopy images of insonated samples showed some
undamaged cells, a few damaged but largely intact cells and comminuted debris.
Cellular damage associated with substantive but incomplete levels of inactivation
can be variable, ranging from membrane holes tens of nanometers in diameter to
nearly complete comminution.
PMID- 29941215
TI - Effects of Non-thermal, Non-cavitational Ultrasound Exposure on Human Diabetic
Ulcer Healing and Inflammatory Gene Expression in a Pilot Study.
AB - The purpose of this clinical study was to assess, in a limited patient
population, the potential for a novel advanced wound care treatment based on low
frequency (20 kHz) low-intensity (spatial peak temporal peak intensity <100
mW/cm2; i.e., pressure amplitude of 55 kPa) ultrasound (LFLI-US), to affect wound
closure rate in human diabetic foot ulcers (DFUs) and to effect changes in the
relative expression of pro-inflammatory and anti-inflammatory genes. The ratio of
expression of these genes, termed the M1/M2 score because it was inspired by the
transition of macrophages from pro-inflammatory (M1) to anti-inflammatory (M2)
phenotypes as wound healing progresses, was previously presented as a potential
healing indicator for DFUs treated with the standard of care. We previously found
that non-cavitational, non-thermal LFLI-US delivered with a pulse repetition
frequency of 25 Hz was effective at improving wound healing in a pilot study of
20 patients with chronic venous ulcers. In this study, we assessed the potential
for weekly LFLI-US exposures to affect wound healing in patients with diabetic
ulcers, and we analyzed temporal changes in the M1/M2 score in debrided diabetic
wound tissue. Although this was a limited patient population of only 8 patients,
wounds treated with LFLI-US exhibited a significantly faster reduction in wound
size compared with sham-treated patients (p < 0.001). In addition, the value of
the M1/M2 score decreased for all healing diabetic ulcers and increased for all
non-healing diabetic ulcers, suggesting that the M1/M2 score could be useful as
an indicator of treatment efficacy for advanced DFU treatments. Such an indicator
would facilitate clinical decision making, ensuring optimal wound management and
thus contributing to reduction of health care expenses. Moreover, the results
presented may contribute to an understanding of the mechanisms underlying
ultrasonically assisted chronic wound healing. Knowledge of these mechanisms
could lead to personalized or patient-tailored treatment.
PMID- 29941216
TI - Interventional Radiology Management of Tracheal and Bronchial Collapse.
AB - Chondromalacia of the tracheal and bronchial cartilages and redundancy of the
dorsal tracheal membrane result in collapse of the large airways, leading to
coughing and airway obstruction. It most commonly affects small-breed dogs,
although larger-breed dogs, cats, and miniature horses are also sporadically
reported. Dynamic airway imaging is used to confirm the diagnosis. The primary
goal of medical management is to control clinical signs attributable to coughing
and airway inflammation. When this is no longer effective, tracheal stents
provide a minimally invasive, rapid way to restore airway patency. Bronchial
stenting is in its infancy in veterinary medicine.
PMID- 29941217
TI - Response to letter to the editor concerning the article "Safety of long-distance
transfers of patients on acute mechanical circulatory support".
PMID- 29941218
TI - Letter to the editor concerning the article "safety of long-distance transfers of
patients on acute mechanical circulatory support".
PMID- 29941219
TI - Impact of the TAP-like transporter in antigen presentation and phagosome
maturation.
AB - Cross-presentation is thought to require transport of proteasome-generated
peptides by the TAP transporters into MHC class I loading compartments for most
antigens. However, a proteasome-dependent but TAP-independent pathway has also
been described. Depletion of the pool of recycling cell surface MHC class I
molecules available for loading with cross-presented peptides might partly or
largely account for the critical role of TAP in cross-presentation of
phagocytosed antigens. Here we examined a potential role of the homodimeric
lysosomal TAP-like transporter in cross-presentation and in presentation of
endogenous peptides by MHC class II molecules. We find that TAP-L is strongly
recruited to dendritic cell phagosomes at a late stage, when internalized antigen
and MHC class I molecules have been degraded or sorted away from phagosomes.
Cross-presentation of a receptor-targeted antigen in vitro and of a phagocytosed
antigen in vivo, as well as presentation of a cytosolic antigen by MHC class II
molecules, is not affected by TAP-L deficiency. However, accumulation in vitro of
a peptide optimally adapted to TAP-L selectivity in purified phagosomes is
abolished by TAP-L deficiency. Unexpectedly, we find that TAP-L deficiency
accelerates phagosome maturation, as reflected in increased Lamp2b recruitment
and enhanced proteolytic degradation of phagocytosed antigen and in vitro
transported peptides. Although additional experimentation will be required to
definitely conclude on the role of TAP-L in transport of peptides presented by
MHC class I and class II molecules, our data suggest that the principal role of
TAP-L in dendritic cells may be related to regulation of phagosome maturation.
PMID- 29941220
TI - Sezary Syndrome Presenting With Renal Involvement.
AB - Sezary syndrome is a rare aggressive leukemic variant of primary cutaneous T-cell
lymphoma, typically presenting with erythroderma, lymphadenopathy, and an
atypical clonal T-cell population. Though it often involves the spleen and liver,
we report a case of Sezary syndrome with renal involvement that was treated
successfully. Visceral involvement confers a poor prognosis requiring systemic
treatment. The patient we describe was a 66-year-old man who was referred from
Dermatology services for deteriorating kidney function. Polymerase chain reaction
of genomic DNA from skin and kidney biopsies confirmed a clonal T-cell population
matching a population isolated in peripheral blood. The patient was treated
initially with alemtuzumab, which led to a significant improvement in kidney
function, and he has subsequently received a successful allogeneic stem cell
transplant. This case represents a rare cause of decreased kidney function and
highlights the role of biopsy in patients with suspected Sezary syndrome.
PMID- 29941221
TI - TREX1 Mutation Causing Autosomal Dominant Thrombotic Microangiopathy and CKD-A
Novel Presentation.
AB - Renal thrombotic microangiopathy (TMA) involves diverse causes and clinical
presentations. Genetic determinants causing alternate pathway complement
dysregulation underlie a substantial proportion of cases. In a significant
proportion of TMAs, no defect in complement regulation is identified. Mutations
in the major mammalian 3' DNA repair exonuclease 1 (TREX1) have been associated
with autoimmune and cerebroretinal vasculopathy syndromes. Carboxy-terminal TREX1
mutations that result in only altered localization of the exonuclease protein
with preserved catalytic function cause microangiopathy of the brain and retina,
termed retinal vasculopathy and cerebral leukodystrophy (RVCL). Kidney
involvement reported with RVCL usually accompanies significant brain and retinal
microangiopathy. We present a pedigree with autosomal dominant renal TMA and
chronic kidney disease found to have a carboxy-terminal frameshift TREX1 variant.
Although symptomatic brain and retinal microangiopathy is known to associate with
carboxy-terminal TREX1 mutations, this report describes a carboxy-terminal TREX1
frameshift variant causing predominant renal TMA. These findings underscore the
clinical importance of recognizing TREX1 mutations as a cause of renal TMA. This
case demonstrates the value of whole-exome sequencing in unsolved TMA.
PMID- 29941222
TI - The regulatory role of Nrf2 in antioxidants phase2 enzymes and IL-17A expression
in patients with ulcerative colitis.
AB - BACKGROUND: Reactive oxygen species (ROS) is one of the pathogenic factors
responsible for intestinal injury in Ulcerative colitis (UC). Nuclear factor
erythroid-2 related factor 2 (Nrf2) plays a critical role against ROS factors to
conserve epithelial integrity. This study aimed to localize Nrf2 and IL-17A
protein in the inflamed mucosa of patients with ulcerative colitis. The gene
expression of Nrf2 was also correlated with GST-A4 and PRDX1. MATERIALS AND
METHODS: A total of 20 patients and 20 healthy controls with definite UC based on
the clinical criteria were enrolled for this study. The expression pattern of
Nrf2 and IL-17A protein was compared in inflamed and non-inflamed colonic
biopsies by immunohistochemical staining. Nrf2, GST-A4 and PRDX1 gene expression
were determined by real-time polymerase chain reaction (RT-PCR). RESULTS: In
inflamed colonic biopsies, an increased level of Nrf2 protein factor was detected
in epithelial cells. Conversely, IL-17A protein was presented more in mononuclear
cells in mucosa and lamina propria regions. A significant increase of Nrf2, GST
A4 gene expression was observed in both mild and severe patients with ulcerative
colitis. GST-A4 gene expression indicated a high exponential rate in logistic
regression. CONCLUSION: Oxidative stress in inflamed colonic tissue can induce
Nrf2 gene expression. The performance of Nrf2 transcription factor may lead to
the induction of GST-A4 and PRDX1. IL-17A is less detected in intestinal
inflammation, presenting Nrf2 factor. The present findings suggest that Nrf2
function in the gut plays a role in arresting both inflammatory response and
oxidative damages of UC.
PMID- 29941223
TI - Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with
molecular analysis of the VHL gene.
AB - Less than 250 extraneuraxial hemangioblastomas occurring in paraneuraxial or
peripheral sites have been reported to date, sporadically or in the setting of
von Hippel-Lindau disease. Seventeen such cases underwent molecular genetic
analysis, using either the patient's peripheral blood in 9 cases or paraffin
embedded tumor tissue in the rest. VHL gene mutations were documented in 3/9
cases in which DNA from peripheral blood lymphocytes was used, all with
clinically manifest von Hippel-Lindau disease; instead, no VHL gene alterations
were found in all of the 8 cases with sporadic extraneuraxial hemangioblastoma in
which DNA from tumor tissue was analyzed. Our aim is to investigate the molecular
genetic profile of the VHL gene in extraneuraxial hemangioblastoma using paraffin
embedded tumor tissues. The clinical features, histopathology, and molecular
investigations of 10 extraneuraxial hemangioblastomas (7 females, 3 males; median
age: 47 years) are presented herein. The histopathologic diagnosis was supported
by immunohistochemistry (10/10) and electron microscopy (4/10). Molecular genetic
analysis was conducted (10/10) for VHL gene mutations, LOH, and gene promoter
methylation. Two of the present cases were already published with only limited or
no molecular investigations. Four tumors of the present series were
paraneuraxial, and 6 peripheral (2 involved soft tissues, and 4 the kidney). One
tumor was von Hippel-Lindau disease-associated, 1 was classified as
"hemangioblastoma-only VHLD", 7 were sporadic, and one was unknown. All were
histopathologically analogous to their counterpart located inside the central
nervous system. Immunophenotypically, all tumors expressed vimentin, S-100, NSE,
and alpha-inhibin (10/10). Ultrastructurally, unbound lipid droplets filled the
cytoplasms of the stromal cells. Molecular analysis revealed 3 inactivating
mutations (1 germline, two somatic) in the coding sequence of the VHL gene in 2
different extraneuraxial hemangioblastomas, and LOH in 4 (two as a double hit),
all non-renal extraneuraxial hemangioblastomas. Methylation analysis failed to
disclose promoter methylation in any case. In conclusion, we report eight new
cases from the wide category of extraneuraxial hemangioblastomas (4
paraneuraxial, and 4 renal), one of which was von Hippel-Lindau disease
associated and 7 sporadic. VHL gene alterations were found not only in the von
Hippel-Lindau disease-associated tumor, but - for the first time - also in 3
sporadic ones, two of which with novel mutations.
PMID- 29941224
TI - [Role of en face OCT in the diagnosis of syphilitic placoid chorioretinitis].
AB - INTRODUCTION: This is a retrospective case series of three patients presenting
with syphilitic chorioretinitis. The diagnosis of syphilis rests on the
ophthalmologic clinical exam as well as serologic confirmation. We studied the en
face and SD-OCT images upon first consultation and after one month of antibiotic
treatment with penicillin G. RESULTS: Four eyes of three male patients between 40
and 60 years of age all diagnosed with syphilitic placoid chorioretinitis were
studied by en face OCT. Visual acuities upon initial presentation were
unrecordable. On all the en face OCT examinations of the three patients, numerous
small hyperreflective oval lesions were observed within the ellipsoid line and
the retinal pigment epithelium around the macula. These lesions corresponded to
small elevated nodules in the retinal pigment epithelium and interruptions in the
ellipsoid line observed on SD-OCT. One month after treatment for neurosyphilis,
the visual acuity had improved, and the outer retinal lesions had partially
reversed in these eyes. CONCLUSIONS: We documented the characteristic lesions of
syphilitic placoid chorioretinitis by en face OCT. En face OCT allows a more
precise approach to the outer retina for diagnosis and follow-up as well as in
understanding the pathophysiology of the disease.
PMID- 29941225
TI - Pediatric refractory and super-refractory status epilepticus.
AB - PURPOSE: To summarize the available evidence related to pediatric refractory
status epilepticus (RSE) and super-refractory status epilepticus (SRSE), with
emphasis on epidemiology, etiologies, therapeutic approaches, and clinical
outcomes. METHODS: Narrative review of the medical literature using MEDLINE
database. RESULTS: RSE is defined as status epilepticus (SE) that fails to
respond to adequately used first- and second-line antiepileptic drugs. SRSE
occurs when SE persist for 24 h or more after administration of anesthesia, or
recurs after its withdrawal. RSE and SRSE represent complex neurological
emergencies associated with long-term neurological dysfunction and high
mortality. Challenges in management arise as the underlying etiology is not
always promptly recognized and therapeutic options become limited with prolonged
seizures. Treatment decisions mainly rely on case series or experts' opinions.
The comparative effectiveness of different treatment strategies has not been
evaluated in large prospective series or randomized clinical trials. Continuous
infusion of anesthetic agents is the most common treatment for RSE and SRSE,
although many questions on optimal dosing and rate of administration remain
unanswered. The use of non-pharmacological therapies is documented in case series
or reports with low level of evidence. In addition to neurological complications
resulting from prolonged seizures, children with RSE/SRSE often develop systemic
complications associated with polypharmacy and prolonged hospital stay.
CONCLUSION: RSE and SRSE are neurological emergencies with limited therapeutic
options. Multi-national collaborative efforts are desirable to evaluate the
safety and efficacy of current RSE/SRSE therapies, and potentially impact
patients' outcomes.
PMID- 29941226
TI - Locally advanced non-inflammatory breast cancer may be misdiagnosed as
inflammatory breast cancer.
PMID- 29941228
TI - Translational research in psychiatry: The Research Domain Criteria Project
(RDoC).
AB - Despite the consensus achieved in the homogenization of clinical criteria by
categorical psychiatric classification systems (DEM and CIE), they are criticized
for a lack of validity and inability to guide clinical treatment and research. In
this review article we introduce the Research Domain Criteria (RDoC) framework as
an alternative framework for translational research in psychiatry. The RDOC
framework systematizes both research targets and methodology for research in
psychiatry. RDoC is based on a catalogue of neurobiological and neurocognitive
evidence of behaviour, and conceives psychopathology as the phenotypic expression
of alterations of functional domains that are classified into 5psychobiological
systems. The RdoC framework also proposes that domains must be validated with
evidence in 7levels of analysis: genes, molecules, cells, nerve circuits,
physiology, behaviour and self-reports. As opposed to categorical systems focused
on diagnosis, RDoC focuses on the study of psychopathology as a correlate of
detectable functional, biological and behavioural disruption of normal processes.
In order to build a useful psychiatric nosology for guiding clinical
interventions, the RDoC research framework links the neurobiological basis of
mental processes with phenotypical manifestations. Although the RDoC findings
have not yet been articulated into a specific model for guiding clinical
practice, they provide a useful transition system for creating clinical, basic
and epidemiological research hypotheses.
PMID- 29941227
TI - The 8th edition American Joint Committee on gastric cancer pathological staging
classification performs well in a population with high proportion of locally
advanced disease.
AB - BACKGROUND: The 8th edition of AJCC gastric cancer pathological staging system
(AJCC8) derived from the IGCA database needs an external validated in cohorts
with higher proportion of advanced disease. PATIENTS AND METHODS: A total of 5386
gastric cancer patients treated at Chang Gung Memorial Hospital (CGMH) and
Veteran General Hospital in Taipei (TVGH) were enrolled. Clinicopathological data
of the IGCA series and the CGMH/TVGH cohort were compared. Cumulative survival
curves of the CGMH/TVGH cohort as stratified by the AJCC7 and the AJCC8 were
compared. Lymph node ratio (LNR) was analyzed in patients with N3b disease.
RESULTS: Patients in the CGMH/TVGH cohort were older and had more advanced tumor
stage (stage III, 49% versus 26%, p < 0.001) than those in the IGCA cohort. The
median survival of stages IIIA, IIIB, and IIIC as defined by the AJCC 8 were 49,
27 and 15 months, respectively, with narrower 95% confidence intervals, in
comparison with 62, 30 and 18 months, respectively, as defined by the AJCC7. The
AJCC8 exhibited better homogeneity within stages and discriminatory ability
between stages, compared to the AJCC7. Six hundred and four patients with N3b
disease were stratified by LNR into three subgroups, and their median survival
were 31, 17, and 11 months, respectively (p < 0.001). LNR further appeared as a
powerful outcome predictor of N3b disease (HR, 3.1). CONCLUSION: The AJCC8
performs well in patients with high proportion of advanced gastric cancer. We
recommend that LNR is a supplementary prognostic indicator for N3b disease.
PMID- 29941229
TI - Efficacy of corticosteroids versus placebo in impacted third molar surgery:
systematic review and meta-analysis of randomized controlled trials.
AB - The aim of this systematic review was to identify randomized, placebo-controlled
clinical trials investigating the effectiveness of corticosteroids in the control
of pain, oedema, and trismus following third molar surgery, and to analyse the
effects of the type of drug administered and the time and route of drug
administration on the outcomes of interest. Searches were performed in the
PubMed, Scopus, and Cochrane Library databases. This review was structured
according to the Preferred Reporting Items for Systematic Reviews and Meta
Analyses. The search identified 1223 studies. After assessing eligibility based
on the inclusion and exclusion criteria, 17 studies were selected for the
qualitative analysis (a total of 730 patients aged 15-45 years). Ten studies were
included in the meta-analysis, which was performed using Review Manager software.
The corticosteroids were effective in controlling pain (P=0.002; mean difference
17.38, 95% confidence interval -24.81 to -9.95) and trismus (P<0.00001; mean
difference 6.10, 95% confidence interval 3.42 to 8.77). With the exception of the
submucosal route, the route of administration did not appear to affect the
outcomes. The administration of a corticosteroid in the preoperative phase was
superior to its use in the postoperative phase for the control of trismus.
PMID- 29941231
TI - Soluble ST2 suppresses IL-5 production by human basophilic KU812 cells, induced
by epithelial cell-derived IL-33.
AB - BACKGROUND: Epithelial cell-derived IL-33 has an important role in the initiation
and activation of innate allergic inflammation. IL-33 acts as a cytokine through
the ST2 receptor (ST2L) and it stimulates the production of Th2 cytokines.
Soluble ST2 (sST2) may regulate Th2 responses by neutralizing the activity of IL
33. Basophils express ST2L and produce IL-5 in response to IL-33. However, the
role of the epithelial cell-basophil interaction and sST2 in IL-5 production
remains unclear. METHODS: Cultured human bronchial epithelial (hBE33) cells, that
contained the human IL-33 gene (i.e., hBE33 cells) and a human basophilic cell
line, KU812 cells, were used to study the epithelial cell-basophil interaction in
the production of IL-5 induced by HDM. RESULTS: At 15 min after incubation, HDM
stimulated the rapid release of IL-33 from cultured hBE33 cells. IL-33 and the
supernatant of HDM-treated hBE33 cells stimulated IL-5 production from KU812
cells. Anti-IL-33 antibody and anti-ST2 antibody treatment of KU812 cells
suppressed IL-5 production, which had been induced by the supernatant of HDM
treated hBE33 cells. The hBE33 cells secreted sST2 in a time-dependent manner.
The production of sST2 by KU812 cells co-cultured with hBE33 cells was
significantly increased, compared with KU812 cells cultured with the supernatant
of hBE33 cells. Soluble ST2 suppressed IL-5 production by KU812 cells, which was
induced by the supernatant of HDM-treated hBE33 cells. CONCLUSIONS: Epithelial
cell-derived IL-33 promoted IL-5 production by KU812 cells. The subsequently
produced sST2 has important roles in regulating Th2 responses.
PMID- 29941232
TI - Treatment of Gliomas: A Changing Landscape.
PMID- 29941230
TI - Gene Regulatory Network Perturbation by Genetic and Epigenetic Variation.
AB - Gene regulatory networks underlie biological function and cellular physiology.
Alternative splicing (AS) is a fundamental step in gene regulatory networks and
plays a key role in development and disease. In addition to the identification of
aberrant AS events, an increasing number of studies are focusing on molecular
determinants of AS, including genetic and epigenetic regulators. We review here
recent efforts to identify various deregulated AS events as well as their
molecular determinants that alter biological functions, and discuss clinical
features of AS and their druggable potential.
PMID- 29941233
TI - Intravenous fish oil containing lipid emulsion attenuates inflammatory cytokines
and the development of bronchopulmonary dysplasia in very premature infants: A
double-blind, randomized controlled trial.
AB - BACKGROUND & AIMS: Preterm infants have lower levels of long-chain
polyunsaturated fatty acids (LCPUFAs). Supplementing very premature infants with
intravenous lipid emulsions that fish oil, which is rich in n-3 LC-PUFAs, may
decrease bronchopulmonary dysplasia (BPD) by modulating inflammation and neonatal
immune function. METHODS: Sixty very low birth weight (VLBW) premature infants
requiring ventilator support were randomized in a double-blind manner to 2 groups
and received total parenteral nutrition with fish oil containing LE (intervention
group, n = 30) or soybean oil containing LE (control group, n = 30) for 7 days.
Blood samples and bronchoalveolar lavage fluid (BALF) were obtained for assay on
day 1 and 7 days after LE. The primary outcome was to compare the levels of
interleukin (IL)-1beta and IL-6 in serum and BALF. Secondary outcomes were to
compare mortality and co-morbidities. RESULTS: The levels of IL-1beta and IL-6 in
serum and BALF were significantly lower in the intervention group at day 8 (p <
0.05). The incidence of BPD in the intervention group compared to the control
group was 13.3% versus 36.7% (p = 0.04; odds ratio [OR], 0.36; 95% confidence
interval [CI], 0.21-0.86). The duration of ventilator support and oxygen use was
significantly less in the intervention group than in the control group (p <
0.05). The level of alanine aminotransferase was significantly lower in the
intervention group on day 8 (p = 0.031). CONCLUSIONS: In very premature infants,
early administration of fish oil containing LE significantly decreased IL-1beta
and IL-6 levels in serum and BALF and was associated with shorter duration of
ventilator support and less bronchopulmonary dysplasia (BPD). TRIAL REGISTRATION
NUMBER: ISRCTN 11427103.
PMID- 29941234
TI - Using Google to Survey PNPs About Agricultural Safety.
AB - INTRODUCTION: Youth and children in agriculture are highly vulnerable to the
health hazards associated with agricultural work and the rural environment.
METHODS: The purpose of this study was to conduct a national needs assessment for
developing a continuing education unit that increases the knowledge of pediatric
nurse practitioners (PNPs) on safety in an agricultural environment using the
Google family of products. This was a cross-sectional, one-group design
descriptive-correlational study. RESULTS: Surveys were received from 315
participants. On Day 1, 57% of responses were received, and 91% were received
within Week 1. DISCUSSION: The use of the free Google Forms and Google Sheets
facilitated this researcher to obtain a sample size, saving research expense
dollars, and entering data file into SPSS. In addition, a pattern of survey
return rates was demonstrated. Second, clinical implications indicate that
agricultural safety is missing from PNP curricula: PNPs are not knowledgeable
about existing resources and would be interested in a continuing education unit.
PMID- 29941235
TI - Factors Associated With Healthy Lifestyle Behaviors Among Adolescents.
AB - OBJECTIVE: Guided by cognitive theory, this study tested an explanatory model for
adolescents' beliefs, feelings, and healthy lifestyle behaviors and sex
differences in these relationships. METHODS: Structural equation modeling
evaluated cross-sectional data from a healthy lifestyle program from 779
adolescents 14 through 17 years old. RESULTS: Theoretical relationships among
thoughts, feelings, and behaviors were confirmed and sex differences identified.
Thoughts had a direct effect on feelings and an indirect effect through feelings
on healthy behaviors for both sexes. A direct effect from thoughts to behaviors
existed for males only. DISCUSSION: Findings provide strong support for the
thinking-feeling-behaving triangle for adolescents. To promote healthy lifestyle
behaviors in adolescents, interventions should incorporate cognitive behavioral
skills-building activities, strengthening healthy lifestyle beliefs, and
enhancing positive health behaviors.
PMID- 29941236
TI - Mindfulness-Based Interventions Among Adolescents With Chronic Diseases in
Clinical Settings: A Systematic Review.
AB - INTRODUCTION: We aimed to determine the benefits/efficacy of mindfulness-based
interventions (MBIs) implemented among adolescents with chronic diseases in
clinical settings. METHODS: An electronic search of PubMed, CINAHL, and PsycINFO
databases was conducted in November 2017 to identify studies in which mindfulness
was the primary intervention delivered for adolescents with chronic diseases to
improve psychological and physical health. RESULTS: Nineteen eligible studies
were included in this review. Fifteen studies included adolescents with
psychiatric or pain disorders, and four included adolescents with a chronic
physical disorders. Psychological outcomes and pain were examined in most studies
with effect sizes for MBIs ranging from small to large. DISCUSSION: MBI studies
conducted in clinical settings mainly engaged adolescents with psychiatric or
pain disorders. The effectiveness of MBIs on improving psychological outcomes
were inconsistent. Large randomized trials are needed to examine the
effectiveness of MBIs and should expand to include adolescents with chronic
physical diseases.
PMID- 29941238
TI - Congenital agastria as an isolated malformation.
PMID- 29941237
TI - The fourth Mexican consensus on Helicobacter pylori.
AB - Important advances have been made since the last Mexican consensus on the
diagnosis and treatment of Helicobacter pylori (H. pylori) infection was
published in 2007. Therefore, the Asociacion Mexicana de Gastroenterologia
summoned 20 experts to produce "The Fourth Mexican Consensus on Helicobacter
pylori". From February to June 2017, 4 working groups were organized, a
literature review was performed, and 3 voting rounds were carried out, resulting
in the formulation of 32 statements for discussion and consensus. From the
ensuing recommendations, it was striking that Mexico is a country with an
intermediate-to-low risk for gastric cancer, despite having a high prevalence of
H. pylori infection. It was also corroborated that peptic ulcer disease,
premalignant lesions, and histories of gastric cancer and mucosa-associated
lymphoid tissue lymphoma should be considered clear indications for eradication.
The relation of H. pylori to dyspeptic symptoms continues to be controversial.
Eradication triple therapy with amoxicillin, clarithromycin, and a proton pump
inhibitor should no longer be considered first-line treatment, with the following
2 options proposed to take its place: quadruple therapy with bismuth (proton pump
inhibitor, bismuth subcitrate, tetracycline, and metronidazole) and quadruple
therapy without bismuth (proton pump inhibitor, amoxicillin, clarithromycin, and
metronidazole). The need for antimicrobial sensitivity testing when 2 eradication
treatments have failed was also established. Finally, the promotion of
educational campaigns on the diagnosis and treatment of H. pylori for both
primary care physicians and the general population were proposed.
PMID- 29941239
TI - Intoxicated aggression: Do alcohol and stimulants cause dose-related aggression?
A review.
AB - RATIONALE: Violence and drug use are significant public health challenges that
are strongly linked. It is known that alcohol plays a major role in the causation
of unnatural deaths and that stimulants like cocaine and amphetamine are often
implicated in aggressive acts or violence. However, a clear causal relationship
between these substances and aggression, and more specifically a blood
concentration threshold at which intoxicated aggression emerges is lacking. In
case of a crime and subsequent law enforcement, knowledge about dose-response
relationships could be of pivotal importance when evaluating the role of alcohol
and drugs in aggressive offences. AIMS: The present review aimed to determine
whether there is a causal relation between intoxication with these psychoactive
substances and aggression, and to define blood concentration thresholds above
which these substances elicit aggression. METHODS: Empirical articles published
between 2013 and 2017 and review papers containing the predefined search strings
were identified through searches in the PubMed and Embase databases and
additional reference list searches. The complete search query yielded 1578
publications. Initially all articles were manually screened by title and
abstract. Articles with irrelevant titles, given the selected search terms and
review aims were discarded. Remaining articles were carefully studied and those
that did not comply with the main objectives of this review were discarded. At
the end of this process, 167 titles were found eligible for review. FINDINGS AND
CONCLUSION: While placebo-controlled experimental studies clearly showed a causal
link between alcohol and aggression, it is evident that such a link has not yet
been established for cocaine and amphetamines. In case of alcohol, it is clear
that there are various individual and contextual factors that may contribute to
the occurrence of an aggressive act during intoxication. A clear threshold blood
alcohol concentration has not been defined yet for alcohol, but a statistically
significant increase of aggression has been demonstrated at a dose of 0.75 g/kg
and higher. Future studies into intoxicated aggression should include multiple
doses of alcohol and stimulants and take into account individual and contextual
factors.
PMID- 29941240
TI - Managing Incidental Findings on Thoracic CT: Mediastinal and Cardiovascular
Findings. A White Paper of the ACR Incidental Findings Committee.
AB - The ACR Incidental Findings Committee presents recommendations for managing
incidentally detected mediastinal and cardiovascular findings found on CT. The
Chest Subcommittee was composed of thoracic radiologists who developed the
provided guidance. These recommendations represent a combination of current
published evidence and expert opinion and were finalized by informal iterative
consensus. The recommendations address the most commonly encountered mediastinal
and cardiovascular incidental findings and are not intended to be a comprehensive
review of all incidental findings associated with these compartments. Our goal is
to improve the quality of care by providing guidance on how to manage
incidentally detected thoracic findings.
PMID- 29941241
TI - Patient-Friendly Summary of the ACR Appropriateness Criteria: Imaging of Deep
Inferior Epigastric Arteries for Surgical Planning (Breast Reconstruction
Surgery).
PMID- 29941242
TI - Artificial Intelligence and Machine Learning: Opportunities for Radiologists in
Training.
PMID- 29941243
TI - Female sex as a biological variable: A review on younger patients with acute
coronary syndrome.
AB - Although acute coronary syndrome (ACS) mainly occurs in individuals >60 years,
younger adults can be affected as well. Women continue to be at higher risk of 30
day mortality after ST-segment elevation myocardial infarction (STEMI) even in
the current era of percutaneous coronary intervention (PCI). Importantly, the
excess mortality among women is only significant at younger ages. Previous work
has suggested that the reason for the differences in outcome is likely
multifactorial and may partially be explained by some of the following factors:
atypical presentation, delayed presentation, under-recognition of STEMI at
initial medical contact, and underuse of medications because of concern regarding
increased risk of bleeding. While these hypotheses may be true in some occasions,
recent studies pointed out that the proportion of women presenting within 2 h
after symptom onset was greater in the younger than in older cohorts. In
addition, sex differences in administration of adjunctive medical therapies were
greater in the older than in the younger cohort. Thus, there is not any one of
the abovementioned factors able to explain the increase in mortality in the young
women. Disparities alone could not account for the gap in mortality across sexes.
Unless the effects of sex are studied, we will continue to have gaps in the
knowledge of potential different mechanisms leading young women and men to die
after ACS, which may result in missed opportunities for implementing a better
health in our community. Randomizing or balancing the sexes as well as powering
studies to detect sex differences is warranted in future research.
PMID- 29941244
TI - Maternal exposure to specific perfluoroalkyl substances is associated with
increasing blood glucose in pregnant women.
PMID- 29941245
TI - Relationship between PM10 and PM2.5 levels in high-traffic area determined using
path analysis and linear regression.
AB - The objective of this study was to determine the relationship between PM10 and
PM2.5 levels as related to meteorological conditions and traffic flow using both
a linear regression analysis and a path analysis. The Particulate matter (PM)
samples were collected from Sukhumvit road, Bangkok, Thailand, at both open (104
samples) and covered (92 samples) areas along the road. Fifteen percent of all
samples were separated before the statistical models were run and used for model
validation. The results from the path analysis were more elaborate than those
from the linear regression, thus indicating that meteorological conditions had a
direct effect on the particulate levels and that the effects of traffic flow were
more variable in open areas. The model also indicated that meteorological
conditions had an indirect effect and that traffic flow had a direct effect on
particulate levels in covered areas. The model validation results indicated that
for open areas, the R2 values were not very different between the path analysis
and the linear regression model, but that the path analysis was more accurate
than the linear regression model at very low PM concentrations. At high PM
concentrations, the path analysis model also had a better fit than did the linear
regression, so the predictions from the path analysis model were more accurate
than those from the linear regression.
PMID- 29941246
TI - Photocatalytic properties of hierarchical CuO nanosheets synthesized by a
solution phase method.
AB - CuO nanomaterials were synthesized by a simple solution phase method using
cetyltrimethylammonium bromide (CTAB) as a surfactant and their photocatalytic
property was determined towards the visible-light assisted degradation of
Reactive Black-5 dye. A detailed mechanism for the formation of CuO
nanostructures has been proposed. The effect of various experimental parameters
such as catalyst amount, dye concentration, pH and oxidizing agent on the dye
degradation efficiency was studied. About 87% dye was degraded at pH2 in the
presence of CuO nanosheets under visible light. The enhanced photocatalytic
activity of CuO nanosheets can be ascribed to good crystallinity, grain size,
surface morphology and a strong absorption in the visible region. CuO is found to
be a promising catalyst for industrial waste water treatment.
PMID- 29941247
TI - Long-term effects of environmentally relevant concentrations of silver
nanoparticles on microbial biomass, enzyme activity, and functional genes
involved in the nitrogen cycle of loamy soil.
AB - The increasing production and use of engineered silver nanoparticles (AgNP) in
industry and private households are leading to increased concentrations of AgNP
in the environment. An ecological risk assessment of AgNP is needed, but it
requires understanding the long term effects of environmentally relevant
concentrations of AgNP on the soil microbiome. Hence, the aim of this study was
to reveal the long-term effects of AgNP on soil microorganisms. The study was
conducted as a laboratory incubation experiment over a period of one year using a
loamy soil and AgNP concentrations ranging from 0.01 to 1 mg AgNP/kg soil. The
short term effects of AgNP were, in general, limited. However, after one year of
exposure to 0.01 mg AgNP/kg, there were significant negative effects on soil
microbial biomass (quantified by extractable DNA; p = 0.000) and bacterial
ammonia oxidizers (quantified by amoA gene copy numbers; p = 0.009). Furthermore,
the tested AgNP concentrations significantly decreased the soil microbial
biomass, the leucine aminopeptidase activity (quantified by substrate turnover; p
= 0.014), and the abundance of nitrogen fixing microorganisms (quantified by nifH
gene copy numbers; p = 0.001). The results of the positive control with AgNO3
revealed predominantly stronger effects due to Ag+ ion release. Thus, the
increasing toxicity of AgNP during the test period may reflect the long-term
release of Ag+ ions. Nevertheless, even very low concentrations of AgNP caused
disadvantages for the microbial soil community, especially for nitrogen cycling,
and our results confirmed the risks of releasing AgNP into the environment.
PMID- 29941248
TI - Characterizing the antibiotic resistance genes in a river catchment: Influence of
anthropogenic activities.
AB - Previous studies on environmental antibiotics resistance genes (ARGs) have
focused on the pollution sources such as wastewater treatment plants, aquaculture
and livestock farms, etc. Few of them had addressed this issue in a regional
scale such as river catchment. Hence, the occurrence and abundances of 23 ARGs
were investigated in surface water samples collected from 38 sites which located
from the river source to estuary of the Beijiang River. Among them, 11 ARGs were
frequently detected in this region and 5 ARGs (sulI, sulII, tetB, tetC, and tetW)
were selected for their distribution pattern analysis. The abundances of the
selected ARGs were higher in the upstream (8.70*106copies/ng DNA) and downstream
areas (3.17*106copies/ng DNA) than those in the midstream areas
(1.23*106copies/ng DNA), which was positively correlated to the population
density and number of pollution sources. Pollution sources of ARGs along the
Beijiang River not only had a great impact on the abundances and diversity, but
also on the distribution of specific ARGs in the water samples. Both sulI and
sulII were likely originated from aquaculture farms and animal farms, tetW gene
was possibly associated with the mining/metal melting industry and the electric
waste disposal and tetC gene was commonly found in the area with multiple
pollution sources. However, the abundance of tetB was not particularly related to
anthropogenic impacts. These findings highlight the influence of pollution
sources and density of population on the distribution and dissemination of ARGs
at a regional scale.
PMID- 29941249
TI - Effect of ozone injection on the long-term performance and microbial community
structure of a VOCs biofilter.
AB - For biofilters treating waste gases containing volatile organic compounds (VOCs),
biomass accumulation is a common problem which will induce bed clogging and
significant decrease in VOCs removal efficiency during long-term operation. In
this study, ozone injection was developed as a biomass control strategy, and its
effects on the biofilter performance and the microbial community structure were
investigated in long-term operation. Two biofilters, identified as BF1 and BF2,
were operated continuously for 160 days treating gaseous toluene under the same
conditions, except that 200 mg/m3 ozone was continuously injected into BF1 during
days 45-160. During the operation period, ozone injection did not change the
toluene removal efficiency, while the pressure drop of BF1 with ozone injection
was significantly lowered compared with BF2. The wet biomass accumulation rate of
BF1 was 11 g/m3/hr, which was only 46% of that in BF2. According to the carbon
balance result, ozone injection also increased the toluene mineralization rate
from 83% to 91%, which could be an important reason for the low biomass
accumulation. The PMA-qPCR result indicated that ozone injection increased the
microbial viability of the biofilm. The high-throughput sequencing result also
revealed that the dominant phyla and genera were not changed significantly by
ozone injection, but some ozone-tolerant genera such as Rhodanobacter, Dokdonella
and Rhodococcus were enhanced by ozone exposure. All the results verified that
ozone injection is capable of sustaining the long-term performance of biofilters
by lowering the biomass accumulation, increasing the microbial viability and
changing the microbial community structure.
PMID- 29941250
TI - Comparisons of two serious air pollution episodes in winter and summer in
Beijing.
AB - Characteristics of two serious air pollution episodes (9-15 January, as the
winter case; and 30 June to 1 July, as the summer case), which occurred in
Beijing in 2013 were investigated and compared using multi-method observations
and numerical simulations. During these two air pollution episodes, PM2.5
concentrations varied significantly within Beijing, with PM2.5 concentrations in
southern parts of Beijing being significantly higher than in northern areas.
Typically, heavy air pollution episodes begin in the southern parts and disperse
towards the northern parts of Beijing. Clearly, synoptic patterns and the
stability of atmospheric circulation patterns were the main factors controlling
air pollution in Beijing. During the winter case, a warm center above 900hPa
occurred over Beijing. Meanwhile, in the summer case, although there was only a
weak inversion, the convective inhibition energy was strong (over 200J/kG). This
clearly influenced the duration of the air pollution event. Except for the local
accumulation and secondary atmospheric reactions in both cases, regional straw
burnings contributed a lot to the PM2.5 concentrations in summer case. Using the
CAMx model, we established that regional transport contributed almost 59% to the
PM2.5 averaged concentration in Beijing in the winter case, but only 31% in the
summer case. Thus, the winter case was a typical regional air pollution episode,
while the summer case resulted from local accumulation straw burnings
transportation and strong secondary atmospheric reactions. Given that air
pollution is a regional problem in China, consistent and simultaneous
implementation of regional prevention and control strategies is necessary to
improve regional air quality.
PMID- 29941251
TI - Allowance and allocation of industrial volatile organic compounds emission in
China for year 2020 and 2030.
AB - As an effective pollution control method, emission allowance and allocation just
implemented in volatile organic compounds (VOCs) control strategy of China in
2016. This article presents a possible way to set the emission allowance targets
and establishes an allowance allocation model for the object year, 2020 and 2030,
using 2010 as the reference year. On the basis of regression and scenario
analysis method, the emission allowance targets were designed, which were
17.902Tg and 18.224Tg for 2020 and 2030, with an increasing rate of 28.75% and
31.06% compared to 2010. From the perspective of industries, processes using VOCs
containing products, like machinery and equipment manufacturing, would continue
to be the most significant industrial VOCs emission sources in the future of
China. Four allocation indicators were selected, which are per capita GDP of each
province, per capita industrial VOCs emission of each province, the economic
contribution of industrial sector to regional economy of each province, and the
emission intensity per land area of each province, respectively. Based on
information entropy, the weights of the indicators were calculated and an
emission allocation model was established, and the results showed that provinces
like Shandong, Jiangsu, Guangdong, Zhejiang and Fujian were calculated to obtain
more emission allowance while burden more reduction responsibility. Meanwhile,
provinces like Guizhou, Ningxia, Hainan, Qinghai and Xizang were on the contrary.
This paper suggests governments to enhance or ease to industrial VOCs reduction
burden of each province in order to stimulate its economy or change its way of
economy development.
PMID- 29941252
TI - Effects of turbulence on carbon emission in shallow lakes.
AB - Turbulent mixing is enhanced in shallow lakes. As a result, exchanges across the
air-water and sediment-water interfaces are increased, causing these systems to
be large sources of greenhouse gases. This study investigated the effects of
turbulence on carbon dioxide (CO2) and methane (CH4) emissions in shallow lakes
using simulated mesocosm experiments. Results demonstrated that turbulence
increased CO2 emissions, while simultaneously decreasing CH4 emissions by
altering microbial processes. Under turbulent conditions, a greater fraction of
organic carbon was recycled as CO2 instead of CH4, potentially reducing the net
global warming effect because of the lower global warming potential of CO2
relative to CH4. The CH4/CO2 flux ratio was approximately 0.006 under turbulent
conditions, but reached 0.078 in the control. The real-time quantitative PCR
analysis indicated that methanogen abundance decreased and methanotroph abundance
increased under turbulent conditions, inhibiting CH4 production and favoring the
oxidation of CH4 to CO2. These findings suggest that turbulence may play an
important role in the global carbon cycle by limiting CH4 emissions, thereby
reducing the net global warming effect of shallow lakes.
PMID- 29941253
TI - Performance of bimetallic nanoscale zero-valent iron particles for removal of
oxytetracycline.
AB - In this study, bimetallic nanoscale zero-valent iron particles (nZVI), including
copper/nanoscale zero-valent iron particles (Cu/nZVI) and nickel/nanoscale zero
valent iron particles (Ni/nZVI), were synthesized by one-step liquid-phase
reduction and applied for oxytetracycline (OTC) removal. The effects of contact
time and initial pH on the removal efficiency were studied. The as-prepared
nanoscale particles were characterized by scanning electron microscopy (SEM),
energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD). Finally, the
degradation mechanisms of OTC utilizing the as-prepared nanoparticles were
investigated by using X-ray photoelectron spectroscopy (XPS) and mass
spectrometry (MS). Cu/nZVI presented remarkable ability for OTC degradation and
removed 71.44% of OTC (100mg/L) in 4hr, while only 62.34% and 31.05% of OTC was
degraded by Ni/nZVI and nZVI respectively. XPS and MS analysis suggested that OTC
was broken down to form small molecules by .OH radicals generated from the
corrosion of Fe0. Cu/nZVI and Ni/nZVI have been proved to have potential as
materials for application in OTC removal because of their significant degradation
ability toward OTC.
PMID- 29941254
TI - Recovery of Cu(II) from aqueous solution by induced crystallization in a long
term operation.
AB - The feasibility of copper recovery by induced crystallization in a long period
(174days) was investigated in a seeded fluidized bed reactor (FBR). The process
was divided into 3 periods according to different influent conditions, and the
period III was separated into III-a and III-b due to the adjustment of the molar
ratio of CO32- concentration to copper concentration ([CT]/[Cu2+]). The removal
efficiency could exceed 95% and the average effluent copper concentration
decreased to 3.0mg/L. The mean particle size of seed grains with copper crystals
coating on, raised to 0.36mm from initial 0.18mm. During period III-a, the
supersaturation exceeded 2.88*104, the removal efficiency decreased to 60%-80%
and the particle size dropped to 0.30mm, due to the generation of fines by
homogeneous crystallization and seeds breaking. And the morphology of the
crystals on the seed grains changed from rod-like to spherical which lead to the
particle size decreasing. In period III-b, the supersaturation was modified by
adjusting the molar ratio of [CT]/[Cu2+] to 1.2 from 2. The efficiency was back
to 95% and the mean particle size grew to 0.36mm at the end of III-b, the
crystals coating on the seeds turned back to rod-like products of good stability.
This study illustrated that the copper salt crystal could keep on growing on the
seed grains for over 150days, the feasibility and controllability of copper
recovery by induced crystallization process in FBR were satisfactory, even under
the dramatic changes in influent conditions.
PMID- 29941255
TI - Characterization of bacterial community and iron corrosion in drinking water
distribution systems with O3-biological activated carbon treatment.
AB - Bacterial community structure and iron corrosion were investigated for simulated
drinking water distribution systems (DWDSs) composed of annular reactors
incorporating three different treatments: ozone, biologically activated carbon
and chlorination (O3-BAC-Cl2); ozone and chlorination (O3-Cl2); or chlorination
alone (Cl2). The lowest corrosion rate and iron release, along with more Fe3O4
formation, occurred in DWDSs with O3-BAC-Cl2 compared to those without a BAC
filter. It was verified that O3-BAC influenced the bacterial community greatly to
promote the relative advantage of nitrate-reducing bacteria (NRB) in DWDSs.
Moreover, the advantaged NRB induced active Fe(III) reduction coupled to Fe(II)
oxidation, enhancing Fe3O4 formation and inhibiting corrosion. In addition, O3
BAC pretreatment could reduce high-molecular-weight fractions of dissolved
organic carbon effectively to promote iron particle aggregation and inhibit
further iron release. Our findings indicated that the O3-BAC treatment, besides
removing organic pollutants in water, was also a good approach for controlling
cast iron corrosion and iron release in DWDSs.
PMID- 29941256
TI - Removal of VOCs from gas streams with double perovskite-type catalysts.
AB - Double perovskite-type catalysts including La2CoMnO6 and La2CuMnO6 are first
evaluated for the effectiveness in removing volatile organic compounds (VOCs),
and single perovskites (LaCoO3, LaMnO3, and LaCuO3) are also tested for
comparison. All perovskites are tested with the gas hourly space velocity (GHSV)
of 30,000hr-1, and the temperature range of 100-600 degrees C for C7H8 removal.
Experimental results indicate that double perovskites have better activity if
compared with single perovskites. Especially, toluene (C7H8) can be completely
oxidized to CO2 at 300 degrees C as La2CoMnO6 is applied. Characterization of
catalysts indicates that double perovskites own unique surface properties and are
of higher amounts of lattice oxygen, leading to higher activity. Additionally,
apparent activation energy of 68kJ/mol is calculated using Mars-van Krevelen
model for C7H8 oxidation with La2CoMnO6 as catalyst. For durability test, both
La2CoMnO6 and La2CuMnO6 maintain high C7H8 removal efficiencies of 100% and 98%,
respectively, at 300 degrees C and 30,000hr-1, and they also show good resistance
to CO2 (5%) and H2O(g) (5%) of the gas streams tested. For various VOCs including
isopropyl alcohol (C3H8O), ethanal (C2H4O), and ethylene (C2H4) tested, as high
as 100% efficiency could be achieved with double perovskite-type catalysts
operated at 300-350 degrees C, indicating that double perovskites are promising
catalysts for VOCs removal.
PMID- 29941257
TI - Preliminary investigation on cytotoxicity of fluorinated polymer nanoparticles.
AB - As well-known persistent organic pollutants (POPs), organofluorine pollutants
such as perfluorooctane sulfonate (PFOS) have been proven to be bioaccumulated
and harmful to health. However, toxicological assessment of organofluorinated
nanoparticles, which have emerged as a novel tool for biomedical and industrial
applications, is lacking, to the best of our knowledge. To assess the biological
effects and health risk of fluorinated nanoparticles, trifluoroethyl aryl ether
based fluorinated poly(methyl methacrylate) nanoparticles (PTFE-PMMA NPs) were
synthesized with various fluorine contents (PTFE-PMMA-1 NPs 12.0wt.%, PTFE-PMMA-2
NPs 6.1wt.% and PTFE-PMMA-3 NPs 5.0wt.%), and their cytotoxicity was investigated
in this study. The in vitro experimental results indicated that the cytotoxicity
of PTFE-PMMA NPs was mild, and was closely related to their fluorine (F) contents
and F-containing side chains. Specifically, the cytotoxicity of PTFE-PMMA NPs
decreased with increasing F content and F-containing side chains. After exposure
to PTFE-PMMA NPs at a sublethal dose (50MUg/mL) for 24hr, the phospholipid
bilayer was damaged, accompanied by increasing permeability of the cell membrane.
Meanwhile, the intracellular accumulation of reactive oxygen species (ROS)
occurred, resulting in the increase of DNA damage, cell cycle arrest and cell
death. Overall, the PTFE-PMMA NPs were found to be relatively safe compared with
typical engineered nanomaterials (ENMs), such as silver nanoparticles and
graphene oxide, for biomedical and industrial applications.
PMID- 29941258
TI - Production and characterization of bioaerosols for model validation in spacecraft
environment.
AB - This study aimed to evaluate the suitability of two bioaerosol generation systems
(dry and wet generation) for the aerosolization of microorganisms isolated from
the International Space Station, and to calibrate the produced bioaerosols to
fulfill the requirements of computational fluid dynamics model (CFD) validation.
Concentration, stability, size distribution, agglomeration of generated
bioaerosol and deposition of bioaerosols were analyzed. In addition, the
dispersion of non-viable particles in the air was studied. Experiments proved
that wet generation from microbial suspensions could be used for the production
of well-calibrated and stabile bioaerosols for model validation. For the
simulation of the natural release of fungal spores, a dry generation method
should be used. This study showed that the used CFD model simulated the spread of
non-viable particles fairly well. The mathematical deposition model by Lai and
Nazaroff could be used to estimate the deposition velocities of bioaerosols on
surfaces, although it somewhat underestimated the measured deposition velocities.
PMID- 29941259
TI - Using X-ray computed tomography and micro-Raman spectrometry to measure
individual particle surface area, volume, and morphology towards investigating
atmospheric heterogeneous reactions.
AB - Heterogeneous reactions on the aerosol particle surface in the atmosphere play
important roles in air pollution, climate change, and global biogeochemical
cycles. However, the reported uptake coefficients of heterogeneous reactions
usually have large variations and may not be relevant to real atmospheric
conditions. One of the major reasons for this is the use of bulk samples in
laboratory experiments, while particles in the atmosphere are suspended
individually. A number of technologies have been developed recently to study
heterogeneous reactions on the surfaces of individual particles. Precise
measurements on the reactive surface area, volume, and morphology of individual
particles are necessary for calculating the uptake coefficient, quantifying
reactants and products, and understanding the reaction mechanism better. In this
study, for the first time we used synchrotron radiation X-ray computed tomography
(XCT) and micro-Raman spectrometry to measure individual CaCO3 particle
morphology, with sizes ranging from 3.5-6.5MUm. Particle surface area and volume
were calculated using a reconstruction method based on software three-dimensional
(3-D) rendering. The XCT was first validated with high-resolution field-emission
scanning electron microscopy (FE-SEM) to acquire accurate CaCO3 particle surface
area and volume estimates. Our results showed an average difference of only 6.1%
in surface area and 3.2% in volume measured either by micro-Raman spectrometry or
X-ray tomography. X-ray tomography and FE-SEM can provide more morphological
details of individual CaCO3 particles than micro-Raman spectrometry. This study
demonstrated that X-ray computed tomography and micro-Raman spectrometry can
precisely measure the surface area, volume, and morphology of an individual
particle.
PMID- 29941260
TI - Phosphine production in anaerobic wastewater treatment under tetracycline
antibiotic pressure.
AB - The influence of tetracycline (TC) antibiotics on phosphine (PH3) production in
the anaerobic wastewater treatment was studied. A lab-scale anaerobic baffled
reactor with three compartments was employed to simulate this process. The
reactor was operated in a TC-absence wastewater and 250MUg/L TC-presence
wastewater for three months after a start-up period, respectively. The responses
of pH, oxidation-reduction potential (ORP), chemical oxygen demand (COD), total
phosphorus (TP), enzymes activity (dehydrogenase and acid phosphatase), and
microbial community were investigated to reveal the effect of TC on PH3
production. Results suggested that the dehydrogenase (DH) activity, acid
phosphatase (ACP) activity and COD have positive relationship with PH3
production, while pH, ORP level and the TP in liquid phase have negative
relationship with PH3 production. With prolonged TC exposure, decrease in pH and
increase in DH activity are beneficial to PH3 production, while decrease in COD
and ACP activity are not the limiting factors for PH3 production.
PMID- 29941261
TI - Formation process and mechanism of humic acid-kaolin complex determined by
carbamazepine sorption experiments and various characterization methods.
AB - To explore the formation process and mechanism of organic matter and organic
mineral complex under humification and mineralization conditions, a series of
samples including humic acid, kaolin, and humic acid-kaolin complex were prepared
using a subcritical water treatment method (SWT) under specific temperature,
pressure and reaction time conditions. HA was used as a surrogate for natural
organic matter because it has a similar abundant pore structure, variety of
carbon types, and chemical components. These samples were used in carbamazepine
(CBZ) sorption experiments and characterized by a variety of techniques. The
polymerization of humic acid under the conditions of increased temperature and
pressure resulted in an increase in specific surface area and molecular quantity.
In addition, the degree of aromaticity rose from 59.52% to 70.90%. These changes
were consistent with the transformation from 'soft carbon' to 'hard carbon' that
occurs in nature. The results of sorption experiments confirmed the interaction
between humic acid and kaolin from the difference between the predicted and
actual Qe values. The conceptual model of humic acid-kaolin complex could be
deduced and described as follows. Firstly, the aromatic components of humic acid
preferentially combine with kaolin through the intercalation effect, which
protects them from the treatment effects. Next, the free carboxyl groups and
small aliphatic components of humic acid interact on the surface of kaolin, and
these soft species transform into dense carbon through cyclization and
polymerization. As a result, humic acid-kaolin complex with a mineral core and
dense outer carbonaceous patches were formed.
PMID- 29941262
TI - Relationship between physicochemical properties and dewaterability of
hydrothermal sludge derived from different source.
AB - Sewage sludge (SS) and deinking sludge (DS) were used to comparatively study the
hydrothermal dewatering of sludge with different components. For a better
overview, an insight into the relationship between physicochemical properties and
dewaterability of hydrothermal sludge was provided. Results found that not all
kinds of sludge were suitably conditioned by hydrothermal treatment (HT) in term
of the elevation of dewaterability. Higher hydrothermal temperature tended to
enhance the dewaterability of SS rather than DS, which was supported by the
variation of their physicochemical properties (including water distribution,
bonding energy, extracellular polymeric substance (EPS), particles size, acid
functional groups and zeta potential in this study). In addition, the changes in
surface morphology suggested that the reverse effect of HT on sludge
dewaterability was mainly due to their dewatering behavior. For SS, the
destruction of EPS structure leaded to the release of bound water, thereby
strengthening sludge dewatering. Conversely, "Bridging effect" generated by
lignocellulose in DS was beneficial for sludge dewatering; however, the
increasing hydrothermal temperature degraded part of lignocellulose and weakened
"bridging effect", finally resulting in worse dewaterability of DS.
PMID- 29941263
TI - Distribution and sources of polycyclic aromatic hydrocarbons and phthalic acid
esters in water and surface sediment from the Three Gorges Reservoir.
AB - After the impoundment of the Three Gorges Reservoir (TGR), the hydrological
situation of the reservoir has changed greatly. The concentration and
distribution of typical persistent organic pollutants in water and sediment have
also changed accordingly. In this study, the concentration, distribution and
potential sources of 16 polycyclic aromatic hydrocarbons (PAHs) and 6 phthalic
acid esters (PAEs) during the water drawdown and impoundment periods were
investigated in water and sediment from the TGR. According to our results, PAHs
and PAEs showed temporal and spatial variations. The mean SigmaPAH and SigmaPAE
concentrations in water and sediment were both higher during the water
impoundment period than during the water drawdown period. The water samples from
the main stream showed larger SigmaPAH concentration fluctuations than those from
tributaries. Both the PAH and PAE concentrations meet the Chinese national water
environmental quality standard (GB 3838-2002). PAH monomers with 2-3 rings and 4
rings were dominant in water, and 4-ring and 5-6-ring PAHs were dominant in
sediment. Di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) were
the dominant PAE pollutants in the TGR. DBP and DEHP had the highest
concentrations in water and sediment, respectively. The main source of PAHs in
water from the TGR was petroleum and emissions from coal and biomass combustion,
whereas the main sources of PAHs in sediments included coal and biomass
combustion, petroleum, and petroleum combustion. The main source of PAEs in water
was domestic waste, and the plastics and heavy chemical industries were the main
sources of PAEs in sediment.
PMID- 29941264
TI - Polar organic tracers in PM2.5 aerosols from an inland background area in
Southwest China: Correlations between secondary organic aerosol tracers and
source apportionment.
AB - PM2.5 aerosol samples were collected over 12 hr and 24 hr intervals in an inland
background area, Gongga Mountain National Nature Reserve (hereafter shortened to
Gongga), during the summer of 2011. Polar organic tracers, inorganic ions and
meteorological data were measured. The purpose of this work was to investigate
the variation patterns, formation and sources of the secondary organic aerosol
tracers in the studied atmosphere. The average concentrations of isoprene
oxidation products, alpha-pinene oxidation products, beta-caryophyllinic acid,
sugars, sugar alcohols and anhydrosugars were 88.6 +/- 106.1, 3.6 +/- 5.7, 0.13
+/- 0.30, 13.6 +/- 13.1, 31.9 +/- 31.4 and 14.8 +/- 10.7 ng/m3 respectively in
all aerosol samples. The aged alpha-pinene second organic aerosol (SOA) tracers
(i.e., 3-hydroxyglutraric acid (3HGA), 3-hydroxy-2,2-dimethylglutaric acid
(HDMGA), 3-acetylpentandioic acid (APDA) and 3-methyl-1,2,3-butanetricarboxylic
acid (MBTCA)) correlated significantly with each other in the 24 hr PM2.5 aerosol
samples, indicating that OH. is the major factor controlling the formation of
these alpha-pinene SOA tracers. Using the positive matrix factorization (PMF)
model and the tracer-based source apportionment method, we calculated that
isoprene oxidation products, alpha-pinene oxidation products, sesquiterpene
oxidation products, biomass burning, fungi spores and anthropogenic SOA accounted
for 21.9% +/- 5.5%, 8.4% +/- 2.1%, 3.0% +/- 0.7%, 5.2% +/- 5.3%, 5.0% +/- 6.2%
and 31.4% +/- 7.8% of organic carbon respectively during the sampling period.
PMID- 29941265
TI - Long-term effects of sliver nanoparticles on the abundance and activity of soil
microbiome.
PMID- 29941266
TI - Development of an on-line measurement system for water-soluble organic matter in
PM2.5 and its application in China.
AB - Water-soluble organic matter (WSOM) represents a critical fraction of fine
particles (PM2.5) in the air, but its changing behaviors and formation mechanisms
are not well understood yet, partly due to the lack of fast techniques for the
ambient measurements. In this study, a novel system for the on-line measurement
of water-soluble components in PM2.5, the particle-into-liquid sampler (PILS)
Nebulizer-aerosol chemical speciation monitor (ACSM), was developed by combining
a PILS, a nebulizer, and an ACSM. High time resolution concentrations of WSOM,
sulfate, nitrate, ammonium, and chloride, as well as mass spectra, can be
obtained with satisfied quality control results. The system was firstly applied
in China for field measurement of WSOM. The mass spectrum of WSOM was found to
resemble that of oxygenated organic aerosol, and WSOM agreed well with secondary
inorganic ions. All evidence collected in the field campaign demonstrated that
WSOM could be a good surrogate of secondary organic aerosol (SOA). The PILS
Nebulizer-ACSM system can thus be a useful tool for intensive study of WSOM and
SOA in PM2.5.
PMID- 29941267
TI - Sulfur dioxide and o-xylene co-treatment in biofilter: Performance, bacterial
populations and bioaerosols emissions.
AB - Sulfur dioxide (SO2) and benzene homologs are frequently present in the off-gas
during the process of sewage sludge drying. A laboratory scale biofilter was set
up to co-treat SO2 and o-xylene in the present study. SO2 and o-xylene could be
removed simultaneously in a single biofilter. Their concentration ratio in the
inlet stream influenced the removal efficiencies. It is worth noting that the
removal of SO2 could be enhanced when low concentrations of o-xylene were
introduced into the biofilter. Pseudomonas sp., Paenibacillus sp., and Bacillus
sp. were the main functional bacteria groups in the biofilter. Sulfur-oxidizing
bacteria (SOB) and o-xylene-degrading bacteria (XB) thrived in the biofilter and
their counts as well as their growth rate increased with the increase in amount
of SO2 and o-xylene supplied. The microbial populations differed in counts and
species due to the properties and components of the compounds being treated in
the biofilter. The presence of mixed substrates enhanced the diversity of the
microbial population. During the treatment process, bioaerosols including
potentially pathogenic bacteria, e.g., Acinetobacter lwoffii and Aeromonas sp.,
were emitted from the biofilter. Further investigation is needed to focus on the
potential hazards caused by the bioaerosols emitted from waste gas treatment
bioreactors.
PMID- 29941268
TI - Association of serum levels of perfluoroalkyl substances with gestational
diabetes mellitus and postpartum blood glucose.
AB - This study was conducted to examine the association of perfluoroalkyl substance
(PFAS) exposure with gestational diabetes mellitus (GDM) risk and postpartum
fasting blood glucose. We used a 1:2 matched case-control study with 84 GDM
subjects and 168 healthy pregnant women from Beijing, China. The maternal blood
was collected at 1-2days before delivery, and eight linear isomers and fourteen
branched isomers were determined in maternal serum. Logistic regression analyses
were performed to evaluate the associations after adjusting for potential
confounders. The median of the sum of levels of total PFASs was 4.24ng/mL with a
interquartile range (IQR) of 2.82-6.54ng/mL. Although maternal PFAS exposure was
not associated with risk of GDM, significant positive associations were observed
between evaluated exposure to specific PFAS congeners and increasing blood
glucose. The odds ratio (ORs) of the highest category of postpartum fasting blood
glucose for perfluoro-1-metylheptylsulfonat (1m-PFOS), perfluoro-3/4
metylheptylsulfonat (3m+4m-PFOS), perfluoro-5-metylheptylsulfonat (5m-PFOS), and
perfluorohexane sulfonate (PFHxS) were 2.03 (95% CI: 1.09-3.77), 1.93 (95% CI:
1.04-3.58), 2.48 (95% CI: 1.33-4.65), and 2.26 (95% CI: 1.21-4.21), respectively,
suggesting negative effects of maternal exposure to specific PFAS compounds on
glucose metabolism.
PMID- 29941269
TI - Effects of C/N ratio on nitrate removal and floc morphology of
autohydrogenotrophic bacteria in a nitrate-containing wastewater treatment
process.
AB - The effects of C/N ratio of a nitrate-containing wastewater on nitrate removal
performed by autohydrogenotrophic bacteria as well as on the morphological
parameters of floc such as floc morphology, floc number distribution, mean
particle size (MPS), aspect ratio and transparency were examined in this study.
The results showed that the nitrate reduction rate increased with increasing C/N
ratio from 0.5 to 10 and that the nitrogen removal of up to 95% was found at the
C/N ratios of higher than 5 (between 0.5-10). Besides, high C/N ratio values
reflected a corresponding high nitrite accumulation after 12-hr operation, and a
fast decreasing rate of nitrite in the rest of operational time. The final pH
values increased with the C/N ratio increasing from 0.5 to 2.5, but decreased
with the C/N ratio increasing from 2.5 to 10. There were no significant changes
in floc morphology with the MPSs ranging from 35 to 40MUm. Small and medium-sized
flocs were dominant in the sludge suspension, and the number of flocs increased
with the increasing C/N ratios. Furthermore, the highest apparent frequency of
10% was observed at aspect ratios of 0.5 and 0.6, while the transparency of flocs
changed from 0.1 to 0.7.
PMID- 29941270
TI - TOF-SIMS surface analysis of chemical components of size-fractioned urban
aerosols in a typical heavy air pollution event in Beijing.
AB - Size-fractioned atmospheric aerosol particles were collected during a typical
heavy air pollution event in Beijing. The organic and inorganic components on the
surfaces of the samples were analyzed using time-of-flight secondary ion mass
spectrometry (TOF-SIMS). The variation characteristics of the surface chemical
composition and influencing factors were studied, and the possible sources of
these chemical compositions were identified through principal component analysis.
The results showed that inorganic components such as crustal elements and
sulfate, and organic components such as aliphatic hydrocarbons and oxygen
containing organic groups were present. Some surface components, such as
polycyclic aromatic hydrocarbons, heavy metals and fluorides may exert adverse
effects on human health. The species and relative percentages of the chemical
components varied with particle size, diurnal and pollution progress. During a
heavy pollution event, the species and relative percentages of secondary
components such as oxygen-containing organic groups and sulfurous compounds
increased, indicating that particles aged during this event. The surface chemical
composition of the aerosol particles was affected mainly by emissions from coal
combustion and motor vehicles. In addition, air pollution, meteorological
factors, and air mass transport also exerted a significant effect on the surface
chemical composition of aerosol particles.
PMID- 29941271
TI - Carbon dioxide adsorption and cycloaddition reaction of epoxides using chitosan
graphene oxide nanocomposite as a catalyst.
AB - One of today's major challenges is to provide green materials for a cleaner
environment. We have conducted studies on carbon dioxide (CO2) adsorption and
conversion to valuable products by an ecofriendly approach based in
chitosan/graphene oxide (CSGO) nanocomposite film. Rheological behavior indicates
that the CSGO has a better solvation property than the pure chitosan. An
adsorption capacity of 1.0152mmolCO2/g of CSGO nanocomposite at 4.6bar was
observed. The catalytic behavior of the CSGO nanocomposite in the presence of
tetra-n-butylammonium iodide (n-Bu4NI) as co-catalyst was evaluated for the
cycloaddition of CO2 to epoxides, to give cyclic carbonates, in the absence of
any solvent. These results strongly suggest that the CSGO nanocomposite may open
new vistas towards the development of ecofriendly material for catalytic
conversion and adsorption of CO2 on industrial scale.
PMID- 29941272
TI - Determination of quorum-sensing signal substances in water and solid phases of
activated sludge systems using liquid chromatography-mass spectrometry.
AB - The detection of acyl homoserine lactones (AHLs) in activated sludge is essential
for clarifying their function in wastewater treatment processes. An LC-MS/MS
method was developed for the detection of AHLs in both the aqueous and solid
phases of activated sludge. In addition, the effects of proteases and
extracellular polymeric substances (EPS) on the detection of AHLs were evaluated
by adding protease inhibitors and extracting EPS, respectively. Recoveries of
each AHL were improved by adding 50MUL of protease inhibitor, and recoveries were
also improved from 0 to 56.9% to 24.2%-105.8% by EPS extraction. Applying the
developed method to determine the type and concentration of AHLs showed that C4
HSL, C6-HSL, C8-HSL and 3-oxo-C8-HSL were widely detected in a suspended
activated sludge system. The dominant AHL was C8-HSL, with a highest
concentration of 304.3ng/L. C4-HSL was mainly distributed in the aqueous phase,
whereas C6-HSL, C8-HSL and 3-oxo-C8-HSL were preferentially distributed in the
sludge phase.
PMID- 29941273
TI - Simulating the fate of indigenous antibiotic resistant bacteria in a mild slope
wastewater polluted stream.
AB - The fate of indigenous surface-water and wastewater antibiotic resistant bacteria
in a mild slope stream simulated through a hydraulic channel was investigated in
outdoor experiments. The effect of (i) natural (dark) decay, (ii) sunlight, (iii)
cloudy cover, (iv) adsorption to the sediment, (v) hydraulic conditions, (vi)
discharge of urban wastewater treatment plant (UWTP) effluent and (vii) bacterial
species (presumptive Escherichia coli and enterococci) was evaluated. Half-life
time (T1/2) of E. coli under sunlight was in the range 6.48-27.7min (initial
bacterial concentration of 105CFU/mL) depending on hydraulic and sunlight
conditions. E. coli inactivation was quite similar in sunny and cloudy day
experiments in the early 2hr, despite of the light intensity gradient was in the
range of 15-59W/m2; but subsequently the inactivation rate decreased in the
cloudy day experiment (T1/2=23.0min) compared to sunny day (T1/2=17.4min). The
adsorption of bacterial cells to the sediment (biofilm) increased in the first
hour and then was quite stable for the remaining experimental time. Finally, when
the discharge of an UWTP effluent in the stream was simulated, the proportion of
indigenous antibiotic resistant E. coli and enterococci was found to increase as
the exposure time increased, thus showing a higher resistance to solar
inactivation compared to the respective total populations.
PMID- 29941274
TI - Efficacy of PCR-based open reading frame typing assay for outbreak investigation
of metallo-beta-lactamase-producing Pseudomonas aeruginosa in hematology unit.
AB - We investigated the efficacy of the PCR-based open reading frame typing (POT)
assay for outbreak investigation of metallo-beta-lactamase (MBL)-producing
Pseudomonas aeruginosa (MBL-PA). A total of 53 P. aeruginosa isolates were
detected between January 2010 and December 2012 on a hematology ward, of which 6
were identified as MBL-PA with the blaIMP-1 gene. The POT assay revealed the same
genotype (207-41) in 3 of 6 MBL-PA, suggesting an outbreak caused by a single
strain. Environmental investigation of bathroom samples revealed the same POT
genotype (207-41) as those of the clinical isolates and no other MBL-PA strains.
Genetic relatedness of the MBL-PA isolates was confirmed by the DiversiLab
repetitive-sequence-based PCR typing system, suggesting the POT type 207-41 as a
genetically identical clone. The POT assay can be successfully applied to MBL-PA
genotyping.
PMID- 29941275
TI - Active surveillance in response to the identification of a single carbapenemase
producing Escherichia coli at a Japanese university hospital.
AB - This report described the experience of active surveillance culture implemented
in response to the identification of a single carbapenemase-producing Escherichia
coli in a Japanese university hospital. It revealed a horizontal transmission
event and an additional asymptomatic carrier of carbapenemase-producing
Escherichia coli with unique drug susceptibility and resistance gene profiles.
Early implementation of active surveillance culture as a part of multifaceted
infection control measures appeared to be useful to control further transmission
of carbapenemase-producing Escherichia coli even in the low endemic facility.
Further investigations on the timing and usefulness of active surveillance
culture in the control of carbapenemase-producing Enterobacteriaceae would be
warranted.
PMID- 29941276
TI - The 10-Group Classification System-a new way of thinking.
PMID- 29941277
TI - December 2017 (vol. 217, no. 6, pages 678.e1-9).
PMID- 29941278
TI - Vaginal progesterone is an alternative to cervical cerclage in women with a short
cervix and a history of preterm birth.
PMID- 29941279
TI - Universal cystoscopy at the time of benign hysterectomy: a debate.
AB - Injury to the bladder and/or ureters is the cause of significant morbidity, and
efforts to reduce these injuries are important. This debate presents arguments
that both support, and refute, the value of routine cystoscopy at the time of
benign hysterectomy. Proponents of routine cystoscopy state that injuries are
more likely to be detected and repaired when cystoscopy is routinely performed.
Dissenters counter that the available evidence does not support routine
cystoscopy at the current rates of lower urinary tract injury, and the cystoscopy
should be performed only when injury is suspected or when performing hysterectomy
with concurrent procedures that increase the risk of lower urinary tract injury.
PMID- 29941281
TI - The role of age in pancreatic intraductal papillary mucinous neoplasms of the
pancreas: Same risk of death but different implications for management.
AB - BACKGROUND: Current guidelines do not address the role of age in the management
of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. AIM: To
evaluate whether clinical features and risk for malignancy are affected by
patient's age at diagnosis. METHODS: In total, 2189 IPMNs, both surgically
resected or surveilled, were dichotomized according to a 50-year-old cutoff and
compared in terms of pathological features, cumulative risk of developing high
risk stigmata (HRS), overall survival (OS) and disease-specific survival (DSS).
RESULTS: Patients <50 years had more frequent abdominal pain (38.5 vs. 22.4%; p <
0.01) and acute pancreatitis (20.4 vs. 9.3%; p < 0.01) at presentation. Patients
>=50 years old had more multifocal IPMNs (50 vs. 36.9%; p < 0.01), HRS (8.5% vs.
4.3%; p = 0.04) and invasive IPMNs (26.6% vs. 17.3%; p = 0.03) when resected.
Moreover, patients >=50 years old had a significantly higher cumulative risk of
developing HRS over time, and a significantly lower OS, but similar DSS when
compared with those <50 years old. CONCLUSIONS: IPMNs diagnosed in older patients
are more likely to progress to HRS despite the fact that cancer-related death is
not affected by age. The follow-up schedule should not be adjusted according to
age, but one should take into account that IPMNs in younger individuals have more
time to progress toward malignancy.
PMID- 29941280
TI - Addition of dose-intensified doxorubicin to standard chemotherapy for
rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised
controlled, phase 3 trial.
AB - BACKGROUND: Rhabdomyosarcoma is an aggressive tumour that can develop in almost
any part of the body. Doxorubicin is an effective drug against rhabdomyosarcoma,
but its role in combination with an established multidrug regimen remains
controversial. Therefore, we aimed to evaluate the possible benefit of early dose
intensification with doxorubicin in patients with non-metastatic
rhabdomyosarcoma. METHODS: We did a multicentre, open-label, randomised
controlled, phase 3 trial involving 108 hospitals from 14 countries. We included
patients older than 6 months but younger than 21 years with a pathologically
proven diagnosis of rhabdomyosarcoma. We assigned each patient to a specific
subgroup according to the EpSSG stratification system. Those with embryonal
rhabdomyosarcoma incompletely resected and localised at unfavourable sites with
or without nodal involvement, or those with alveolar rhabdomyosarcoma without
nodal involvement were considered at high risk of relapse. These high-risk
patients were randomly assigned (1:1) to receive either nine cycles of IVA
(ifosfamide 3 g/m2 given as a 3-h intravenous infusion on days 1 and 2,
vincristine 1.5 mg/m2 weekly during the first 7 weeks then only on day 1 of each
cycle [given as a single intravenous injection], and dactinomycin 1.5 mg/m2 on
day 1 given as a single intravenous injection) or four cycles of IVA with
doxorubicin 30 mg/m2 given as a 4-h intravenous infusion on days 1 and 2 followed
by five cycles of IVA. The interval between cycles was 3 weeks. Randomisation was
done using a web-based system and was stratified (block sizes of four) by
enrolling country and risk subgroup. Neither investigators nor patients were
masked to treatment allocation. The primary endpoint was 3-year event-free
survival assessed by the investigator at each centre in the intention-to-treat
population. Patients who received at least one dose of study treatment were
considered in the safety analysis. In agreement with the independent data
monitoring committee, the study was closed to patient entry on Dec 16, 2013,
after futility analysis. This trial is registered with EudraCT, number 2005
000217-35, and is currently in follow-up. FINDINGS: Between Oct 1, 2005, and Dec
16, 2013, 484 patients were randomly assigned to receive each chemotherapy
regimen (242 in the IVA group and 242 in the IVA plus doxorubicin group). Median
follow-up was 63.9 months (IQR 44.6-78.9). The 3-year event-free survival was
67.5% (95% CI 61.2-73.1) in the IVA plus doxorubicin group and 63.3% (56.8-69.0)
in the IVA group (hazard ratio 0.87, 95% CI 0.65-1.16; p=0.33). Grade 3-4
leucopenia (232 [93%] of 249 patients in the IVA plus doxorubicin group vs 194
[85%] of 227 in the IVA group; p=0.0061), anaemia (195 [78%] vs 111 [49%];
p<0.0001), thrombocytopenia (168 [67%] vs 59 [26%]; p<0.0001), and
gastrointestinal adverse events (78 [31%] vs 19 [8%]; p<0.0001) were
significantly more common in the IVA plus doxorubicin group than in the IVA
group. Grade 3-5 infections (198 [79%] vs 128 [56%]; p<0.0001) were also
significantly more common in the IVA plus doxorubicin group than in the IVA
group, in which one patient had grade 5 infection. Two treatment-related deaths
were reported (one patient developed septic shock and one affected by Goldenhar
syndrome developed intractable seizures) in the IVA plus doxorubicin group, both
occurring after the first cycle of treatment, and none were reported in the IVA
group. INTERPRETATIONS: The addition of dose-intensified doxorubicin to standard
IVA chemotherapy did not show a significant improvement in the outcome of
patients with high-risk non-metastatic rhabdomyosarcoma. Therefore, the IVA
chemotherapy regimen should remain the standard of care for patients with
localised rhabdomyosarcoma in Europe. FUNDING: Fondazione Citta della Speranza,
Italy, and the Association Leon Berard Enfant Cancereux, France.
PMID- 29941282
TI - Dengue vaccine: reliably determining previous exposure.
PMID- 29941283
TI - Gait and functional status analysis before and after total knee arthroplasty.
AB - BACKGROUND: Among the procedures for severe gonarthrosis, total knee arthroplasty
(TKA) is considered a successful method patient satisfaction and functional
improvement; however, TKA is commonly associated with incompletely recovered gait
function. The aim of this study was to evaluate the influence of TKA and
physiotherapy programmes on gait features and patient-reported functional status
and the relationship between them, leading to broader knowledge of the origins of
long-term gait disturbances. METHODS: Walking speed, step length and single
support time were analysed by GAITRite system in 60 healthy controls and 21 TKA
patients analysed at four time points: one day before and five days after surgery
and before and after a three-week rehabilitation (12 and 15 weeks after surgery).
Functional status was assessed using the Western Ontario and McMaster
Osteoarthritis Index (WOMAC). RESULTS: At all time points, the TKA subjects
walked significantly slower than the controls, but walking speed continuously
increased after surgery. Gait asymmetries were observed in single support time
(before surgery) and step length (after surgery). Partial restoration of gait
function was observed 12 weeks after surgery and completion of the rehabilitation
programme. An indirect correlation between gait velocity and function WOMAC
subscores was found. CONCLUSIONS: Patients after TKA were characterised by
significant improvements in self-reported functionality and progressive reduction
of gait abnormalities, probably related to pain reduction. However, at 15 weeks
after surgery, patients exhibited step length asymmetry, which could be
considered as an effect of habits of three-point crutch gait in the early
postoperative period.
PMID- 29941284
TI - Medicare risk-adjusted outcomes in elective major vascular surgery.
AB - BACKGROUND: Risk-adjusted outcomes of elective major vascular surgery that is
inclusive of inpatient and 90-day post-discharge adverse outcomes together have
not been well studied. METHODS: We studied 2012-2014 Medicare inpatients who
received open aortic procedures, open peripheral vascular procedures,
endovascular aortic procedures, and percutaneous angioplasty procedures of the
lower extremity for risk-adjusted adverse outcomes of inpatient deaths, 3-sigma
prolonged length-of-stay outliers, 90-day post-discharge deaths without
readmission, and 90-day post-discharge associated readmissions after excluding
unrelated events. Observed and predicted total adverse outcomes for hospitals
meeting minimum risk-volume criteria were assessed and hospital-specific z-scores
and risk-adjusted adverse outcomes were calculated to compare performance.
RESULTS: The total adverse-outcome rate was 27.8% for open aortic procedures,
31.5% for open peripheral vascular procedures, 19.6% for endovascular aortic
procedures, and 36.4% for percutaneous angioplasty procedures. The difference in
risk-adjusted adverse-outcome rates between the best- and the poorest-performing
deciles were 32.2% for open aortic procedures, 29.5% for open peripheral vascular
procedures, 21.5% for endovascular aortic procedures, and 37.1% for percutaneous
angioplasty procedures. The 90-day post-discharge deaths and readmissions were
the major driver of overall adverse-outcome rates. CONCLUSION: The variability in
risk-adjusted outcomes among best- and poorest-performing hospitals is over 20%
in all major vascular procedures and indicates that a large opportunity exists
for improvement in results.
PMID- 29941285
TI - Proliferative and osteogenic differentiation capacity of mesenchymal stromal
cells: Influence of harvesting site and donor age.
AB - Human mesenchymal stromal cells (hMSCs) are the cellular source of new bone
formation and an essential component of autologous bone grafts. Autologous bone
graft harvesting is routinely conducted at the iliac crest, although alternative
donor sites with lower complication rates are available. Thus, the aim of this
study was to compare hMSCs harvested from the iliac crest and the proximal tibia
regarding their proliferative and osteogenic differentiation capacity.
Furthermore, we investigated the influence of donor age on these biological
properties. HMSCs were isolated from iliac crest or proximal tibia bone grafts of
46 patients. Proliferative capacity was assessed by cumulative population
doublings, population doubling time, colony forming units and cell proliferation
assays. Osteogenic capacity was assessed by quantification of extracellular
calcium deposition and marker gene expression levels. The number of hMSCs per
gram harvested tissue was determined. Furthermore, the adipogenic and
chondrogenic differentiation capacity were quantified using BODIPY and Safranin
Orange staining, respectively. Additional analyses were carried out after
grouping young (18-49 years) and aged (>=50 years) donors. HMSCs derived from the
proximal tibia featured a comparable proliferative and osteogenic differentiation
capacity. No significant differences were found for any analysis conducted, when
compared to hMSCs obtained from the iliac crest. Furthermore, no significant
differences could be revealed when comparing young and aged donors. This was
equally true for hMSCs from both donor sites after comparison within the same age
group. Our study demonstrates comparable biological properties of hMSCs derived
from both donor sites, the iliac crest and the proximal tibia. Furthermore, aging
does not alter proliferative and osteogenic differentiation capacity.
Consequently, the proximal tibia should be considered more closely as an
alternative donor site in patients of all age groups.
PMID- 29941286
TI - How to prevent the next fracture.
AB - During the last decade, policymakers, learned societies, non-governmental
organisations (NGOs) and some national alliances of all three of these groups
have advocated, developed and implemented systematic approaches to fragility
fracture care and prevention in a growing number of countries. This chapter
reviews the impact of Orthogeriatric Services (OGS) and Fracture Liaison Services
(FLS) on delivery of best practice in secondary fracture prevention. An overview
of national and international strategies intended to promote widespread
implementation of these service models is also provided.
PMID- 29941287
TI - Human menstrual blood-derived stem cells promote the repair of impaired
endometrial stromal cells by activating the p38 MAPK and AKT signaling pathways.
AB - Multiple studies have confirmed that human menstrual blood-derived stem cells
(MenSCs) have potential applications in regenerative medicine or cell therapy.
However, the contribution of MenSCs to endometrial repair is currently unknown.
We evaluated the protective effects of MenSCs on impaired endometrial stromal
cells (ESCs), as well as the signaling pathways involved in this process.
Mifepristone was used to damage human ESCs, which were subsequently cocultured
with MenSCs. The proliferation, apoptosis, and migration of ESCs were assessed,
together with the expression of related signaling proteins including total p38
mitogen-activated protein kinase, P-p38, total protein kinase B (AKT), P-AKT,
beta-catenin, and vascular endothelial growth factor (VEGF). MenSCs significantly
recovered the proliferation and migration ability of impaired ESCs, inhibited ESC
apoptosis, and upregulated protein expression of P-AKT, P-p38, VEGF, and beta
catenin. Our findings suggest that MenSC-based therapies could be promising
strategies for the treatment of endometrial injury, and that AKT and p38
signaling pathways may be involved in this process.
PMID- 29941288
TI - Surgical technique and results of intrapancreatic bile duct resection for hilar
malignancy (with video).
AB - BACKGROUND: Hilar malignancy can occasionally be associated with high grade
dysplasia (HGD) adjacent to invasive malignancy. For patients with HGD extending
into the intrapancreatic bile duct, the authors adopted intrapancreatic bile duct
resection (IP-BDR). The aims of this study were to compare the incidence of
clinically relevant postoperative pancreatic fistula (CR-POPF), distal R0
resection and local recurrence within the distal bile duct remnant for patients
undergoing extrahepatic bile duct resection without pancreaticoduodenectomy (with
or without IP-BDR). METHODS: Patients who presented with hilar malignancy and
underwent extrahepatic bile duct resection without pancreaticoduodenectomy
between January 2005 and December 2016 were identified and the outcomes
retrospectively evaluated. RESULTS: Of 217 patients who met the inclusion
criteria 62 (29%) patients underwent IP-BDR. There was a significant difference
between patients undergoing standard resection vs. IP-BDR in terms of CR-POPF (5%
(8/155) patients: vs 18% (11/62), p < 0.001). There were no significant
differences between two groups of R0 status on distal margin (5% (8/155)
patients: vs 10% (6/62), p = 0.359). No patient developed recurrence within the
residual intrapancreatic bile duct. DISCUSSION: The incidence of CR-POPF after IP
BDR for hilar malignancies was 18%. IP-BDR was associated with CR-POF, but does
not appear to alter survival or local recurrence rate.
PMID- 29941289
TI - Management of postoperative pancreatic fistula after pancreatoduodenectomy: high
mortality after completion pancreatectomy: Reply to: Bressan et al. completion
pancreatectomy in the acute management of pancreatic fistula after
pancreaticoduodenectomy.
PMID- 29941290
TI - Probabilistic PCR based near-infrared modeling with temperature compensation.
AB - Considering that temperature makes a difference to near-infrared spectrum, a
probabilistic principle component regression (PPCR) based temperature
compensation modeling strategy is investigated under the framework of maximum
likelihood estimation. First, a PPCR model is established to extract the dynamic
information of the spectra at designated experimental temperature. Then, by
decomposing the temperature-induced spectral variation into the shift in
horizontal direction and the drift in vertical direction, the quantitative
expression between spectral variation and temperature change is derived. Based on
the decomposition, the estimation of new latent variables that vary with
temperature is derived according to the spectral data set collected at certain
temperatures. Finally, for performance evaluation, applications of the
theoretical results to bisphenol-A and gasoline-ethanol mixture illustrate the
effectiveness and advantages of the developed techniques.
PMID- 29941291
TI - Comment on "Linkage analysis of a model quantitative trait in humans: Finger
ridge count shows significant multivariate linkage to 5q14.1" by Medland et al.,
"Common Genetic Variants Influence Whorls in Fingerprint Patterns" by Ho et al.
and "Hot on the Trail of Genes that Shape Our Fingerprints" by Walsh et al .
PMID- 29941292
TI - The Third Revolution in Sequencing Technology.
AB - Forty years ago the advent of Sanger sequencing was revolutionary as it allowed
complete genome sequences to be deciphered for the first time. A second
revolution came when next-generation sequencing (NGS) technologies appeared,
which made genome sequencing much cheaper and faster. However, NGS methods have
several drawbacks and pitfalls, most notably their short reads. Recently, third
generation/long-read methods appeared, which can produce genome assemblies of
unprecedented quality. Moreover, these technologies can directly detect
epigenetic modifications on native DNA and allow whole-transcript sequencing
without the need for assembly. This marks the third revolution in sequencing
technology. Here we review and compare the various long-read methods. We discuss
their applications and their respective strengths and weaknesses and provide
future perspectives.
PMID- 29941293
TI - Screening for Latent Tuberculosis Infection in Patients who are Candidate for
Biological Therapies in Spain? A Multidisciplinary Survey.
AB - INTRODUCTION: Treatment with biological therapies increases the incidence of
tuberculous disease. The introduction of systematic screening for latent
tuberculosis infection in patients who are to receive these therapies has reduced
this risk. In 2016, the consensus document on the prevention and treatment of
tuberculosis in patients who are candidates for biological treatment was
published in Spain. The main objective of this study was to evaluate adherence to
these guidelines. METHODS: Multicenter, descriptive, observational study via an
anonymous online survey sent to medical societies involved in biologics. RESULTS:
We received 747 responses. Most respondents performed screening at the right time
in the right patients (93.7%). Only 36.6% of respondents requested the
appropriate diagnostic test, while 56.3% correctly recommended chemoprophylaxis.
Up to 96% were familiar with the recommended chemoprophylaxis regimens, while
only 63.9% initiated them at the right time. The specialist area that
participated most and screened most patients for latent tuberculosis infection
was rheumatology (54%). In most cases, pulmonologists were involved in an
advisory capacity. CONCLUSIONS: This study shows poor overall adherence to
recommendations, with only 56% of respondents reporting appropriate compliance.
The incidence of tuberculous disease in patients who are to receive biological
therapies could be reduced further by emphasizing the importance of the right
diagnostic test and use of the diagnostic algorithm for latent tuberculosis
infection.
PMID- 29941295
TI - Beneficial and adverse effects of antipsychotic medication on cognitive
flexibility are related to COMT genotype in first episode psychosis.
AB - This study evaluated the ability to flexibly shift cognitive set and to
consistently maintain a new response preference using the Penn Conditional
Exclusion Test (PCET). The relationship of performance errors with catechol-O
methyltransferase (COMT) rs4680 (Val158Met) genotype (Met carriers vs. Val
homozygotes) on test performance before and after antipsychotic treatment in 32
first episode psychosis (FEP) patients was examined. After treatment, patients
demonstrated a mixture of beneficial and adverse cognitive outcomes that varied
in relation to COMT genotype. Met carriers showed decreased perseverative and
regressive errors, reflecting improved cognitive flexibility and enhanced
stability of behavioral preferences, respectively. In contrast, Val homozygotes
exhibited an increase in regressive errors after treatment. These findings
suggest that Val homozygotes may be vulnerable to adverse effects of
antipsychotic medication on cognitive processes that maintain consistent adaptive
response preferences, an ability linked to the striatum in rodent models.
PMID- 29941296
TI - Comparison of the anti-inflammatory effect of aripiprazole and risperidone in 75
drug-naive first episode psychosis individuals: A 3 months randomized study.
AB - INTRODUCTION: Evidence about the anti-inflammatory properties of antipsychotics
has grown. However, no previous studies have compared the immunomodulatory effect
of risperidone and aripiprazole. OBJECTIVES: The main aim of the present work is
to compare the anti-inflammatory effect of risperidone and aripiprazole on a
large array of serum cytokines at 3 months following the onset of treatment.
METHODS: This is a prospective, randomized, open-label study. Patients were
randomly assigned to risperidone or aripiprazole. From this randomization, 75
patients and 75 healthy volunteers that matched with the selected patients were
picked for entry in this study. Serum concentrations of 21 cytokines/chemokines
were measured at baseline and 3 months following the initiation of antipsychotic
medication. RESULTS: Those patients who were randomly assigned to risperidone had
higher levels of IL-8 (p = 0.000) and MIP-1beta (p = 0.007) than healthy
volunteers at baseline, whereas no differences were found between patients
initially assigned to aripiprazole and healthy volunteers. Three months following
the onset of medication several cytokines decreased significantly: IL-8, MIP
1beta, Fractalkine, TNF-alpha, IL-7, IL-13, IL-17alpha, IL-23, IL-21 (all ps <
0.01). No differences were found in the percentages of change between both
treatments. The effect size of the two antipsychotics was similar, except for TNF
alpha, IL-13, IL-17alpha and Fractalkine, in which aripiprazole seems to have a
greater effect size than risperidone, whereas risperidone seems to have a greater
effect size than aripiprazole on MIP-1beta. CONCLUSIONS: This is the first study
that has compared the immunomodulatory effect of risperidone and aripiprazole,
finding that the anti-inflammatory effect of both treatments was similar.
PMID- 29941297
TI - We need reproducible health behaviour change interventions to help adults with
severe mental illness.
PMID- 29941294
TI - Psychiatric disability as mediator of the neurocognition-functioning link in
schizophrenia spectrum disorders: SEM analysis using the Evaluation of Cognitive
Processes involved in Disability in Schizophrenia (ECPDS) scale.
AB - The functional outcome in schizophrenia spectrum disorders is affected by
multiple factors such as cognitive performance and clinical symptoms. Psychiatric
disability may be another important determinant of functional outcome. The
purpose of this study was to test whether schizophrenia symptoms and psychiatric
disability mediated the association between cognition and functioning. Between
April 2013 and July 2017, we included 108 community-dwelling adults with stable
schizophrenia spectrum disorder in a multicenter study. Psychiatric disability
was assessed with the Evaluation of Cognitive Processes involved in Disability in
Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad
array of motivational, neurocognitive, sociocognitive, and metacognitive
impairments that result in activity restrictions. We used a battery of tests to
assess seven cognition domains (processing speed, attention/vigilance, working,
verbal and visual memory, reasoning and problem solving, and executive
functioning) and cross-sectional structural equation modeling (SEM) for the
mediation analyses. We estimated the one-year temporal stability of ECPDS scores
in 45 participants. The model provided showed good fit and explained 43.9% of the
variance in functioning. The effect of neurocognition on functioning was fully
mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability
(proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal
stability. The ECPDS scale has satisfactory psychometric properties, and shows
significant convergence with neurocognition and functioning, suggesting a role
for this tool in the routine evaluation of cognitive remediation needs. Our model
validates psychiatric disability as a crucial step from cognitive impairment to
restricted participation in life situations.
PMID- 29941298
TI - Acoustic waves improves retroviral transduction in human retinal stem cells.
AB - BACKGROUNDS: The plasticity of retinal stem cells (RSCs), a type of cells that
can differentiate into neuron cells and photoreceptor cells, endows them with
potential therapeutic properties that can be applied to regenerative medicine.
Gene modification of these stem cells before trans-differentiation and
transplantation enhances their survival and increases their therapeutic function.
The different ways to effectively deliver gene into RSCs are still discussed.
This study aimed to use the acoustic waves to improve the efficacy of gene
delivery for RSCs. METHODS: RSCs were obtained from non-fetal human ocular
pigmented ciliary margin tissues. The enhanced green fluorescent protein-encoded
murine stem cell retroviruses (MSCV) were prepared and used to infect RSCs. Glass
chambers containing RSCs, retroviruses, and various concentrations of polybrene
(0, 0.8, 2, 4 and 8 MUg/mL) were exposed under 20 or 25 Vp-p ultrasonic standing
wave fields (USWF) for 5 min. The percentage of green fluorescent protein
positive cells in each sample was calculated and compared to test the efficacy of
gene transduction. RESULTS: Our results showed that the efficiency of gene
transduction by MSCV infection was enhanced following the concentration of
polybrene and the energy of USWF. The percentage of green fluorescent protein
positive cells was significantly higher in chambers that contained 8 MUg/mL of
polybrene and was exposed to 20Vp-p of USWF for 5 min. In addition, the
percentage increased in chambers contained 2, 4 and 8 MUg/mL of polybrene when
they were exposed to 25Vp-p of USWF. Comparing to those did not treated with
ultrasound, the efficiency of retroviral transduction to RSCs increased 4-fold
after exposed to USWF for 5 min. CONCLUSION: We demonstrated the ability of
ultrasound standing waves to improve retroviral transduction into RSCs. We
believe that this may be applied to the experimental designs of future studies
and may have possible therapeutic uses.
PMID- 29941299
TI - The phonological loop as a buffer store: An update.
AB - We regard our multicomponent model of working memory as reflecting a hierarchy of
buffer stores with buffer storage providing an effective way of combining
information from two or more streams that may differ in either the speed of input
or in the features coded. We illustrate this through the case of the phonological
loop component of the model. We discuss its gradual development through a
combination of evidence from mainstream cognition and neuropsychology with the
need for more detailed modelling of issues such as the representation of serial
order. A brief account follows of the application, beyond the laboratory and
clinic, of the concept of a phonological loop and the methods designed to study
it. We then discuss some criticisms of the overall multicomponent model,
concluding with a discussion of the major contribution made by neuropsychological
evidence to its development together with some suggestions as to comparative lack
of influence from more recent studies based on neuro-imaging.
PMID- 29941300
TI - Statistical motion modelling for robust evaluation of clinically delivered
accumulated dose distributions after curative radiotherapy of locally advanced
prostate cancer.
AB - BACKGROUND AND PURPOSE: Planned doses are used as surrogate for the actually
delivered dose in radiotherapy. We have estimated the delivered dose in a dose
escalation trial of locally advanced prostate cancer by statistical dose
accumulation and by DVH-summation, and compared to planned dose. MATERIALS AND
METHOD: Prescribed dose-escalation to the prostate was 67.5 Gy/25fr.,
corresponding to 81GyEQD2 assuming alpha/beta = 1.5. The 21 patients had three
targets (i.e. CTV67.5 + 2 mm, CTV60 + 5 mm, CTV50 + 10 mm) irradiated by a
simultaneous-integrated-boost technique. Analysis was based on 213 CT scans and 5
years of follow-up. For statistical dose-accumulation, we modelled 10000 possible
treatment courses based on planned dose and deformation-vector-fields from
contour-based registration. For DVH-summation we recalculated dose on repeat-CTs
and estimated median D98%/EUD. Groups with/without disease recurrence were
compared. RESULTS: Discrepancies between planned and accumulated dose were mostly
seen for CTV67.5, where under-dosage was found at different locations in the
prostate in 12/21 patients. Delivered dose-escalation (D98%) was on average
73.9GyEQD2 (range: 68.3-78.7GyEQD2). No significant difference in accumulated
D98% was found in patients with (n = 8) and without (n = 13) recurrence (p >
0.05). Average D98%/EUD with statistical dose-accumulation vs DVH-summation was
significantly different in CTV60, CTV50, rectum and bladder but not in CTV67.5.
CONCLUSION: The planned dose escalation was not received by more than half-of-the
patients. Robustness of the prostate target (CTV67.5) should therefore be better
prioritized in these patients given the low toxicity profile. Estimates of
delivered dose were less conservative for dose-accumulation due to interaction of
random organ motion with the dose matrix.
PMID- 29941301
TI - Laparoscopic stomach intestinal pylorus-sparing surgery as a revisional option
after failed adjustable gastric banding: a report of 27 cases with 36-month
follow-up.
AB - BACKGROUND: Inadequate weight loss, weight recidivism, and device-related
complications after an adjustable gastric banding (AGB) can be treated by a
laparoscopic conversion to stomach intestinal pylorus-sparing surgery (SIPS).
OBJECTIVE: The aim of the study was to analyze the midterm outcomes of revision
SIPS surgery after failed AGB. SETTING: Private practice, United States. METHODS:
This is a retrospective review of our prospectively collected data of patients
who underwent laparoscopic conversion from AGB to SIPS surgery from June 2013 and
February 2017 by a single surgeon in a single institution. RESULTS: Twenty-seven
patients (1 stage: 22 and 2 stage: 5) underwent a laparoscopic revision of AGB to
SIPS surgery. The mean +/- standard deviation preoperative body mass index (BMI)
before AGB was 47.5 +/- 6.8 kg/m2, while the mean nadir BMI after AGB was 36 +/-
7.7 kg/m2. The overall time to reoperation was 9.3 +/- 8.7 and 5.6 +/- 2.5 years
in 1- and 2-stage conversion patients, respectively. The mean preoperative BMI
before revision SIPS surgery was 46.7 +/- 7 kg/m2. At 36 months, the patients had
an average change in BMI of 20.9 units with 90% excess weight loss. A major
complication occurred in 4 patients. Postoperatively, the fasting blood glucose,
insulin, low-density lipoprotein, triglyceride, and most of the co-morbidities
were resolved or improved. CONCLUSION: This study demonstrates that conversion of
failed AGB to SIPS surgery is an effective approach to AGB failure.
PMID- 29941302
TI - Changes in the lipid profile 5 years after bariatric surgery: laparoscopic Roux
en-Y gastric bypass versus laparoscopic sleeve gastrectomy.
AB - BACKGROUND: Few studies have compared mid-term results of laparoscopic Roux-en-Y
gastric bypass (LRYGB) versus laparoscopic sleeve gastrectomy (LSG), and none
have focused on lipid profile. OBJECTIVES: To compare LRYGB versus LSG with
respect to lipid disturbance evolution and remission at mid-term after bariatric
surgery (BS) and to assess associated factors with the remission of lipid
disturbances at 5 years. SETTING: Hospital del Mar, Barcelona, from January 2005
to January 2012. METHODS: A retrospective analysis of a nonrandomized,
prospective cohort was conducted on patients undergoing BS at Hospital del Mar,
Barcelona, from January 2005 to January 2012 with >=5 years' follow-up. RESULTS:
Of 259 patients, 151 (58.3%) completed the 5-year follow-up. The proportion of
patients who achieved normal low-density lipoprotein cholesterol levels at 5
years post-LRYGB was greater than after LSG (30/49 [61.2%] versus 6/23 [26.1%]; P
= .005), being male sex, absence of statins treatment, and type of BS technique
(LRYGB) the associated factors with remission. Hypertriglyceridemia remission was
also higher after LRYGB (23/25 [92.0%] versus 10/15 [66.7%]; P = .041), although
type of surgery was not an associated factor. No differences were found in
remission rates of low high-density lipoprotein cholesterol between groups.
Absence of fibrates treatment and 5-year percentage of excess weight loss were
independently associated with hypertriglyceridemia remission, and only the latter
was independently associated with low high-density lipoprotein cholesterol
remission 5 years after surgery. CONCLUSIONS: Five-year outcome data showed that,
among patients with severe obesity undergoing BS, LRYGB was associated with a
higher total and low-density lipoprotein cholesterol reduction and remission in
comparison to LSG, with no differences in hypertriglyceridemia and high-density
lipoprotein cholesterol normalization.
PMID- 29941303
TI - Elasticity of the pronator teres muscle in youth baseball players with elbow
injuries: evaluation using ultrasound strain elastography.
AB - BACKGROUND: Although the pronator teres muscle, a major dynamic stabilizer of
elbow valgus stress during throwing, frequently presents stiffness, its
relationship with elbow injuries in youth baseball players is unknown. This study
investigated the relationship between the elasticity of the pronator teres muscle
and elbow injuries in youth baseball players. METHODS: The strain ratio (SR) of
15 individuals with osteochondritis dissecans of the humeral capitellum (OCD
group), 67 individuals with medial epicondylar fragmentation (medial injury
group), and 115 healthy individuals (control group) was measured as the index of
the elasticity of the pronator teres muscle using ultrasound strain elastography.
In addition, the forearm and glenohumeral joint rotation range of motion was
measured. RESULTS: The SR of the throwing arm was significantly higher in the OCD
and medial injury groups than in the control group (both P <.001). In the OCD
group, the SR was significantly higher in the throwing arm than in the
nonthrowing arm (P <.001), whereas in the medial injury group, there was no
significant difference between both arms. The glenohumeral joint external
rotation range of motion of the throwing arm was moderately negatively correlated
with the SR (r = -0.478, P <.001). CONCLUSIONS: Stiffness of the pronator teres
muscle was exhibited only in the throwing arm of individuals with OCD and in both
arms in individuals with medial elbow injury. These findings may contribute to an
accurate evaluation and prevention of elbow injuries in youth baseball players.
PMID- 29941304
TI - A matched quantitative computed tomography analysis of 3 surgical approaches for
osteochondral reconstruction of the capitellum.
AB - BACKGROUND: The location of capitellar osteochondritis dissecans (OCD) lesions in
the sagittal plane guides the surgical approach used for autologous osteochondral
transplantation. We sought to compare the capitellar region accessible for
orthogonal graft placement through 3 approaches: (1) posterior anconeus-split
approach; (2) lateral approach with lateral collateral ligament (LCL)
preservation (LCL-preserving lateral approach); and (3) lateral approach with LCL
release (LCL-sacrificing lateral approach). METHODS: The 3 approaches were
sequentially performed on 9 cadaveric elbows: posterior anconeus-split approach,
LCL-preserving lateral approach, and LCL-releasing lateral approach. The extent
of perpendicular access was delineated with Kirschner wires. Each specimen
underwent computed tomography. The accessible region was quantified as degrees on
the capitellum and converted into time on a clock, where 0 degrees corresponds
to the 12-o'clock position. Generalized estimating equation modeling was used to
investigate for significant within-specimen, between-approach differences.
RESULTS: The LCL-preserving and LCL-sacrificing lateral approaches provided more
anterior perpendicular access than the posterior anconeus-split approach (mean, 0
degrees vs 83 degrees ; P < .001). The posterior anconeus-split approach
provided more posterior perpendicular access (mean, 215.0 degrees ; P < .001)
than the LCL-preserving (mean, 117 degrees ; P < .001) and LCL-sacrificing (mean,
145 degrees ; P < .001) lateral approaches. The LCL-sacrificing lateral approach
provided more posterior exposure than the LCL-preserving lateral approach (mean,
145 degrees vs 117 degrees ; P < .001). The mean arc of visualization was
greater for the LCL-sacrificing lateral approach than for the LCL-preserving
lateral approach (145 degrees vs 117 degrees , P < .001). CONCLUSIONS: A
capitellar OCD lesion can be perpendicularly accessed from a posterior anconeus
split approach if it is posterior to 83 degrees (2:46 clock-face position). A
laterally based approach may be required for lesions anterior to this threshold.
These data inform clinical decisions regarding the appropriate surgical approach
for any OCD lesion.
PMID- 29941305
TI - Anatomic study of pedicled bipolar teres major transfer for irreparable
posterosuperior rotator cuff tears.
AB - BACKGROUND: Treatment of rotator cuff (RC) tears has not included bipolar muscle
tendon transfers to date. The objective of this study was to verify the
feasibility of pedicled bipolar teres major (TM) transfer over and under the long
head of the triceps brachii (LHT) and compare its versatility with monopolar
transfer in a model of supraspinatus (SS) tears in cadavers. METHODS: In 6
shoulders of cryopreserved cadavers, we re-created complete SS tears, conducting
monopolar and bipolar TM transfers over and under LHT. We compared the morphology
of the SS and TM, defect coverage, angle between the transferred TM and major SS
axis, and axillary nerve overlap with each technique. RESULTS: The TM and SS were
morphologically similar. Defect coverage was significantly lower with monopolar
transfer (12 +/- 4 mm) than with bipolar transfer (39 +/- 9 mm under the LHT, P =
.003, and 38 +/- 8 mm over the LHT, P = .004). The bipolar transfer course over
the LHT was the nearest to the SS axis (39 degrees +/- 11 degrees , P = .005).
We found a greater axillary nerve overlap with bipolar transfer under the LHT (27
+/- 8 mm) than with bipolar transfer over the LHT (1 +/- 2 mm, P = .005) or
monopolar transfer (0 mm, P < .001). CONCLUSION: Bipolar TM transfer is possible
without neurovascular pedicle interference, obtaining greater RC defect coverage
and the closest path to the SS axis when conducted over the LHT compared with
monopolar or bipolar transfer under the LHT. Accordingly, it can be considered an
alternative option for the treatment of posterosuperior RC defects.
PMID- 29941306
TI - Development of an infant complete-airway in vitro model for evaluating aerosol
deposition.
AB - A complete-airway in vitro model would be very useful for toxicological dosimetry
testing and for developing targeted inhaled medications in cases where conducting
in vivo experiments are exceedingly difficult, as with infants. The objective of
this study was to determine whether packed bed in vitro models, which contain
spheres as the primary repeating unit, provide a realistic representation of
aerosol deposition in the tracheobronchial region of infant lungs based on
computational fluid dynamics (CFD) predictions. The packed bed (PB) CFD model
contained an inlet consistent with airway bifurcation B3 (~lobar bronchi) leading
to a spherical array with voids between the spheres forming a divided flow
pathway. The hydrodynamic diameter of the voids was approximately matched to the
diameter of bifurcations in various lung regions. For comparison, a CFD
stochastic individual pathway (SIP) geometry with realistic bifurcations
extending from B4-B15 (terminal bronchioles) was selected as an anatomically
accurate model. The CFD-SIP model predictions were benchmarked with existing
algebraic correlations for aerosol deposition in the lungs and found to be
reasonable. Unfortunately, the CFD-PB model did not provide a good representation
of aerosol deposition in the tracheobronchial region of human lungs. Through
careful selection of the PB sphere size and inlet conditions, total deposition in
the CFD-PB model matched CFD-SIP deposition within 10% absolute error across a
range of relevant aerosol sizes. However, regional deposition within the CFD-PB
model was very different from the CFD-SIP case. Therefore, the PB approach cannot
be recommended for determining spatial or temporal distribution of aerosol
transport and impaction deposition through the lungs.
PMID- 29941307
TI - Somatic Bi-allelic Loss of TSC Genes in Eosinophilic Solid and Cystic Renal Cell
Carcinoma.
AB - : Renal cell carcinomas (RCC) with overlapping histomorphologic features poses
diagnostic challenges. This is exemplified in RCCs with eosinophilic cytoplasm
that include eosinophilic solid and cystic RCC (ESC RCC), RCCs in germline
aberrations of tuberous sclerosis complex (TSC) genes mutated (TSC RCC)
individuals, and other RCC subtypes. We used next-generation sequencing (NGS)
technology to molecularly profile seven ESC RCC tumors. Mutational and copy
number analysis of NGS data revealed mutually exclusively somatic bi-allelic loss
of TSC1 or TSC2 genes-both negative regulators of the mammalian target of
rapamycin (mTOR) pathway in 85% (6/7) of evaluated cases. Thus, lack of germline
TSC aberration in matched non-neoplastic renal parenchyma distinguishes ESC RCC
from TSC RCC. Immunohistochemistry data shows mTOR pathway activation in all
tumors, thus supporting a pathognomonic role for TSC aberrations in ESC RCC. Our
study clarifies the molecular identity of ESC RCC, provides basis for the
revision of current RCC classification, and may guide future therapeutic
strategies. PATIENT SUMMARY: Molecular characterization of eosinophilic solid and
cystic renal cell carcinomas (ESC RCC) revealed recurrent and mutually exclusive
somatic homozygous loss of tuberous sclerosis complex family genes. This
observation provides greater insight into the unique biology of this novel type
of tumor and potentially expands the therapeutic options for ESC RCC patients.
PMID- 29941308
TI - Spatial Intratumor Genomic Heterogeneity within Localized Prostate Cancer
Revealed by Single-nucleus Sequencing.
AB - BACKGROUND: Prostate adenocarcinoma (PCa) is a complex genetic disease, and the
implementation of personalized treatment in PCa faces challenges due to
significant inter- and intrapatient tumor heterogeneities. OBJECTIVE: To
systematically explore the genomic complexity of tumor cells with different
Gleason scores (GSs) in PCa. DESIGN, SETTING, AND PARTICIPANTS: We performed
single-cell whole genome sequencing of 17 tumor cells from localized lesions with
distinct GS and matched four normal samples from two prostatectomy patients.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All classes of genomic alterations
were identified, including substitutions, insertions/deletions, copy number
alterations, and rearrangements. RESULTS AND LIMITATIONS: Significant spatial,
intra- and intertumoral heterogeneities were observed at the cellular level. In
the patient 1, all cells shared the same TP53 driver mutation, implying a
monoclonal origin of PCa. In the patient 2, only a subpopulation of cells
contained the TP53 driver mutation, whereas other cells carried different driver
mutations, indicating a typical polyclonal model with separate clonal cell
expansions. The tumor cells from different sides of prostate owned various
mutation patterns. Considerable neoantigens were predicted among different cells,
implying unknown immune editing components helping prostate tumor cells escaping
from immune surveillance. CONCLUSIONS: There is a significant spatial genomic
heterogeneity even in the same PCa patient. Our study also provides the first
genome-wide evidence at single-cell level, supporting that the origin of PCa
could be either polyclonal or monoclonal, which has implications for treatment
decisions for prostate cancer. PATIENT SUMMARY: We reported the first single-cell
whole genomic data of prostate adenocarcinoma (PCa) from different Gleason
scores. Identification of these genetic alterations may help understand PCa tumor
progression and clonal evolution.
PMID- 29941309
TI - Affective communication during bad news consultation. Effect on analogue
patients' heart rate variability and recall.
AB - OBJECTIVE: The aim of the study was to investigate the effect of physicians'
supportive communication on analogue patients' (APs) heart rate variability (HRV)
and recall, while watching a video of palliative treatment being explained to a
female patient. METHODS: Sixty healthy women, acting as APs, were randomly
assigned to watch one of two versions (standard vs. affective) of a scripted
video-vignette of a bad news consultation to a female patient. The physician's
communication differed only in the delivery of four supportive comments. Empathy,
support and engagement perception were assessed by three questions. APs' HR was
recorded during video-observation and recall was assessed immediately after. HRV
was determined through measures defined in time and frequency domains. RESULTS:
Data of 54 APs (27 + 27) were included. The group with supportive communication
perceived the physician as more empathic and supportive. Intra- and Inter-group
comparisons suggested a greater sense of stress in the standard communication
group. Recall did not differ in the two groups. CONCLUSION AND PRACTICE
IMPLICATIONS: Findings show that the use of supportive expressions contribute to
the perception of the physician as more empathic, potentially buffer patients'
arousal after a bad news announcement, but does not confirm a positive impact on
general recall.
PMID- 29941310
TI - How do aging and age-related hearing loss affect the ability to communicate
effectively in challenging communicative conditions?
AB - This study investigated the relation between the intelligibility of
conversational and clear speech produced by older and younger adults and (a) the
acoustic profile of their speech (b) communication effectiveness. Speech samples
from 30 talkers from the elderLUCID corpus were used: 10 young adults (YA), 10
older adults with normal hearing (OANH) and 10 older adults with presbycusis
(OAHL). Samples were extracted from recordings made while participants completed
a problem-solving cooperative task (diapix) with a conversational partner who
could either hear them easily (NORM) or via a simulated hearing loss (HLS), which
led talkers to naturally adopt a clear speaking style. In speech-in-noise
listening experiments involving 21 young adult listeners, speech samples by OANH
and OAHL were rated and perceived as less intelligible than those of YA talkers.
HLS samples were more intelligible than NORM samples, with greater improvements
in intelligibility across conditions seen for OA speech. The presence of
presbycusis affected (a) the clear speech strategies adopted by OAHL talkers and
(b) task effectiveness: OAHL talkers showed some adaptations consistent with an
increase in vocal effort, and it took them significantly longer than the YA group
to complete the diapix task. The relative energy in the 1-3 kHz frequency region
of the long-term average spectrum was the feature that best predicted: (a) the
intelligibility of speech samples, and (b) task transaction time in the HLS
condition. Overall, our study suggests that spontaneous speech produced by older
adults is less intelligible in babble noise, probably due to less energy present
in the 1-3 kHz frequency range rich in acoustic cues. Even mild presbycusis in
'healthy aged' adults can affect the dynamic adaptations in speech that are
beneficial for effective communication.
PMID- 29941311
TI - Contralateral suppression of human hearing sensitivity in single-sided deaf
cochlear implant users.
AB - Cochlear implants (CIs) are being implanted in people with unilateral hearing
loss because they can improve speech intelligibility and sound source
localization. Though designed to restore the afferent auditory stimulation, the
CI possibly restores some efferent effects. The present study aimed at
investigating this possibility. Five single-sided deaf CI users with less than 30
dB hearing loss up to 4 kHz in their acoustic ear participated in the study.
Absolute thresholds for their acoustic ears were measured for pure tones of 500
and 4000 Hz with durations of 10 and 200 ms in the presence and in the absence of
contralateral broadband electrical stimulation (CBES) delivered with the CI. The
electrical stimulus consisted of pulse trains (symmetric biphasic pulses with
phase duration 36 MUs) on all 16 electrodes sequentially stimulated at a rate of
843 Hz. Its intensity was set to sound as loud as broadband noise at 50 or 60 dB
SPL in the acoustic ear. Thresholds were measured using a three-interval, three
alternative, forced-choice procedure with a two-down, one-up adaptive rule to
estimate the level for 71% correct in the psychometric function. Thresholds
measured without the CBES were lower for the longer than for the shorter tones,
and the difference was larger at 500 than at 4000 Hz. CBES equivalent to 50 or 60
dB SPL caused significant threshold elevation only for short (10 ms) and low
frequency (500 Hz) acoustic tones of 1.2 and 2.2 dB. These increases appear
smaller than previously reported for normal hearing listeners in related
experiments. These results support the notion that for single-sided deaf CI
users, the CI modulates hearing in the acoustic ear. The possible mechanisms that
may be contributing this effect are discussed.
PMID- 29941312
TI - Comorbidities of hearing loss and the implications of multimorbidity for
audiological care.
AB - With increasing age, the risk of developing chronic health conditions also
increases, and many older people suffer from multiple co-existing health
conditions, i.e., multimorbidity. One common health condition at older age is
hearing loss (HL). The current article reflects on the implications for
audiological care, when HL is one of several health conditions in a
multimorbidity. An overview of health conditions often co-existing with HL, so
called comorbidities, is provided, including indications for the strength of the
associations. The overview is based on a literature study examining cohort
studies that were published in the years 2010-2018 and examined associations of
hearing loss with other health conditions, namely Visual impairment, Mobility
restrictions, Cognitive impairment, Psychosocial health problems, Diabetes,
Cardiovascular diseases, Stroke, Arthritis, and Cancer. This selection was based
on previous publications on common chronic health conditions at older age and
comorbidities of hearing loss. For all of these health conditions, it was found
that prevalence is larger in people with a HL and several longitudinal studies
also found increased incident rates in people with a HL. The examined
publications provide little information on how hearing loss should be managed in
the clinical care of its comorbidities and vice versa. The current article
discusses several options for adaptations of current care. Nonetheless, solutions
for an integrated audiology care model targeting HL in a multimorbidity are still
lacking and should be subject to future research.
PMID- 29941313
TI - Criteria for the Management of Technological Assets in Cardiovascular Imaging.
AB - Adequate, updated and functional technology is essential in cardiology. In Spain,
the economic scenario has strongly impacted technology renewal programs and
obsolescence is a growing problem. The current report attempts to describe the
current situation and the conditions that must concur to update, replace or adopt
new technologies in the field of cardiology.
PMID- 29941314
TI - Shear rate is a better marker of symptomatic ischemic cerebrovascular events than
velocity or diameter in severe carotid artery stenosis.
AB - OBJECTIVE: This study was designed to test the hypothesis that the high shear
rate of flow in the area of carotid stenosis is associated with the incidence of
ischemic symptoms in patients with a high degree of carotid stenosis. METHODS:
This is a case-control study of patients with >70% stenosis of the internal
carotid artery (ICA) identified by duplex ultrasound in an Intersocietal
Accreditation Commission-accredited laboratory during 1 year. Symptomatic
patients were included in the study group, and asymptomatic patients served as
controls. Shear rates were calculated from high-resolution ultrasound images.
Descriptive statistics and univariate and multivariate analysis were performed to
account for confounding factors. Receiver operating characteristic curves were
used to compare diagnostic values of shear rate, velocities, and diameters of the
ICA. RESULTS: The study included 308 patients (55.5% male; mean age, 73 +/- 10
years); 209 of them were asymptomatic and 99 were symptomatic. The mean shear
rate was 7930 s-1 for asymptomatic and 9338 s-1 for symptomatic patients.
Receiver operating characteristic curve identified a cutoff value of 8000 s-1 to
differentiate between symptomatic and asymptomatic patients; 92% of asymptomatic
patients and 8.0% of symptomatic patients had a shear rate of <8000 s-1 compared
with 48.5% asymptomatic and 51.5% symptomatic who had a shear rate >=8000 s-1.
Patients who had a shear rate higher than this cutoff value were 12 times more
likely to be symptomatic than those with a shear rate <8000 s-1 (odds ratio,
12.1; 95% confidence interval, 6.12-24.09). Sensitivity and specificity were
84.8% and 61.2%, respectively. CONCLUSIONS: In patients with >70% ICA stenosis,
the shear rate is associated with the prevalence of symptomatic cerebrovascular
ischemic events. A shear rate of 8000 s-1 and above may be used as a predictor
for having symptomatic cerebrovascular ischemic events. Further validation as
well as further study of the pathologic mechanism connecting the high shear rate
and ischemic cerebrovascular events is needed.
PMID- 29941315
TI - Outcomes from the Gore Global Registry for Endovascular Aortic Treatment in
patients undergoing thoracic endovascular aortic repair for type B dissection.
AB - OBJECTIVE: The Global Registry for Endovascular Aortic Treatment (GREAT) is a
prospective multicenter registry collecting real-world data on the performance of
W. L. Gore (Flagstaff, Ariz) aortic endografts. The purpose of the present study
was to analyze the implementation and outcomes of thoracic endovascular aortic
repair (TEVAR) in GREAT patients with type B aortic dissection (TBAD). METHODS:
From 2010 to 2016, >5000 patients were enrolled in the GREAT from 113 centers in
14 countries across 4 continents. The study population comprised those treated
for TBAD. The primary outcomes of interest were mortality and freedom from aortic
events (AEs). RESULTS: A total of 264 patients (80% male; mean age, 62 years)
underwent TEVAR for the treatment of 170 (64%) acute and 94 (36%) chronic cases
of TBAD. Chronic TBAD patients required significantly longer endograft coverage
than did acute TBAD patients (P = .05). Early postoperative complications
occurred in 9% of patients, with no difference in chronic vs acute dissection (P
= .11). The 30-day aortic mortality and all-cause mortality were 1.5% and 2.3%,
respectively, with no differences based on chronicity. During a mean follow-up of
26 months, the total aortic mortality was 2.7% and the total all-cause mortality
was 12.5%. The all-cause mortality was significantly greater for chronic vs acute
TBAD (19.2% vs 8.8%, respectively; P = .02). On multivariate analysis, patients
with acute uncomplicated dissections had significantly improved overall survival
compared with all other categories of dissections (93% vs 83% at 2 years; P <
.05). A proximal landing zone diameter >40 mm was associated with an increased
risk of retrograde type A dissection (18% vs 2%; P = .02). Patients undergoing
left subclavian artery (LSA) coverage experienced a twofold greater rate of AEs
compared with noncoverage patients (P < .01). Patients who underwent LSA
revascularization experienced a 1.5-fold greater rate of AEs compared with
patients covered without revascularization (P = .04). CONCLUSIONS: TEVAR for TBAD
using the conformable GORE TAG thoracic endoprosthesis device can be performed
with a low incidence of aortic mortality and complications. Acute uncomplicated
TBAD patients had a significantly lower mortality rate than that of other
patients. Larger proximal landing zones were associated with more frequent
retrograde type A dissection. LSA involvement (coverage and/or revascularization)
was associated with an increased risk of AEs during follow-up.
PMID- 29941316
TI - Transcarotid artery revascularization versus transfemoral carotid artery stenting
in the Society for Vascular Surgery Vascular Quality Initiative.
AB - BACKGROUND: Recent evidence from the Safety and Efficacy Study for Reverse Flow
Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial in
high-risk patients undergoing transcarotid artery stenting with dynamic flow
reversal reported the lowest stroke rate compared with any prospective trial of
carotid artery stenting. However, clinical trials have selection criteria that
exclude many patients from enrollment and are highly selective of operators
performing the procedures, which limit generalizability. The aim of this study
was to compare in-hospital outcomes after transcarotid artery revascularization
(TCAR) and transfemoral carotid artery stenting (TFCAS) as reported in the
Vascular Quality Initiative (VQI). METHODS: The Society for Vascular Surgery VQI
TCAR Surveillance Project (TSP) was designed to evaluate the safety and
effectiveness of TCAR in real-world practice. Data from the initial 646 patients
enrolled in the TSP from March 2016 to December 2017 were analyzed and compared
with those of patients who underwent TFCAS between 2005 and 2017. Patients with
tandem, traumatic, or dissection lesions were excluded. Multivariable logistic
regression and 1:1 coarsened exact matching were used to analyze neurologic
adverse events (stroke and transient ischemic attacks [TIAs]) and in-hospital
mortality. Patients in the two procedures were matched on age, ethnicity,
coronary artery disease, congestive heart failure, prior coronary artery bypass
graft or percutaneous coronary intervention, chronic kidney disease, degree of
ipsilateral stenosis, American Society of Anesthesiologists class, symptomatic
status, restenosis, anatomic and medical risk, and urgency of the procedure.
RESULTS: Compared with patients undergoing TFCAS (n = 10,136), those undergoing
TCAR (n = 638) were significantly older, had more cardiac comorbidities, were
more likely to be asymptomatic, and were less likely to have a recurrent
stenosis. The rates of in-hospital TIA/stroke as well as of TIA/stroke/death were
significantly higher in TFCAS compared with TCAR (3.3% vs 1.9% [P = .04] and 3.8%
vs 2.2% [P = .04], respectively). In both procedures, symptomatic patients had
higher rates of TIA/stroke/death compared with asymptomatic patients (TCAR, 3.7%
vs 1.4% [P = .06]; TFCAS, 5.3% vs 2.7% [P < .001]). After multivariable
adjustment, there was a trend of increased stroke or death rates in TFCAS
compared with TCAR, but it was not statistically significant (2.5% vs 1.7%; P =
.25; odds ratio, 1.75, 95% confidence interval, 0.85-3.62). However, TFCAS was
associated with twice the odds of in-hospital adverse neurologic events and
TIA/stroke/death compared with TCAR (odds ratio, 2.10; 95% confidence interval,
1.08-4.08; P = .03), independent of symptom status. Coarsened exact matching
showed similar results. CONCLUSIONS: Compared with patients undergoing TFCAS,
patients undergoing TCAR had significantly more medical comorbidities but similar
stroke/death rates and half the risk of in-hospital TIA/stroke/death. These
results persisted despite rigorous adjustment and matching of potential
confounders. This initial evaluation of the VQI TSP demonstrates the ability to
rapidly monitor new devices and procedures using the VQI. Although it is
preliminary, this is the first study to demonstrate the benefit of TCAR compared
with TFCAS in real-world practice. These results need to be confirmed by a
clinical trial.
PMID- 29941317
TI - The effect of preoperative cognitive impairment and type of vascular surgery
procedure on postoperative delirium with associated cost implications.
AB - OBJECTIVE: Postoperative delirium (POD) has a high prevalence among vascular
surgery patients, increasing morbidity, mortality, and length of stay. We
prospectively studied preoperative risk factors for delirium that can be assessed
by the surgical team to identify high-risk patients and assessed its impact on
hospital costs. METHODS: There were 173 elective vascular surgery patients
assessed preoperatively for cognitive function using the Montreal Cognitive
Assessment (MoCA) and the Confusion Assessment Method for POD, which was verified
by chart and clinical review. Demographic information, medications, and a history
of substance abuse, psychiatric disorders, and previous delirium were
prospectively recorded. An accompanying retrospective chart review of an
additional 434 (elective and emergency) vascular surgery patients provided
supplemental cost information related to sitter use and prolonged hospitalization
secondary to three factors: delirium alone, dementia alone, and delirium and
dementia. RESULTS: Prospective screening of 173 patients (73.4% male; age, 69.9
+/- 10.97 years) identified that 119 (68.8%) had MoCA scores <24, indicating
cognitive impairment, with 7.5% having severe impairment (dementia). Patients who
underwent amputation had significantly (P < .000) lower MoCA scores (17 of 30)
compared with open surgery and endovascular aneurysm repair patients (23.7 of
30). The incidence of delirium was 11.6% in the elective cohort. Regression
analysis identified predictors of delirium to be type of surgical procedure,
including lower limb amputation (odds ratio [OR], 16.67; 95% confidence interval
[CI], 3.41-71.54; P < .000) and open aortic repair (OR, 5.33; 95% CI, 1.91-14.89;
P < .000); cognitive variables (dementia: OR, 5.63; 95% CI, 2.08-15.01; P <
.001); MoCA scores <=15, indicating moderate to severe impairment (OR, 6.13; 95%
CI, 1.56-24.02; P = .02); and previous delirium (OR, 2.98; 95% CI, 1.11-7.96; P =
.03). Retrospective review (N = 434) identified differences in sitter needs for
patients with both delirium and dementia (mean, 13.6 days), delirium alone (mean,
3.9 days), or dementia alone (mean, <1 day [17.7 hours]). Fifteen patients
required >200 hours (8.3 days), accounting for 69.7% of sitter costs for the
surgical unit; 43.7% of costs were accounted for by patients with pre-existing
cognitive impairment. CONCLUSIONS: POD is predicted by type of vascular surgery
procedure, impaired cognition (MoCA), and previous delirium. Costs and morbidity
related to delirium are greatest for those with impaired cognitive burden.
Preoperative MoCA screening can identify those at highest risk, allowing
procedure modification and informed care.
PMID- 29941318
TI - RNA sequencing data from neutrophils of patients with cystic fibrosis reveals
potential for developing biomarkers for pulmonary exacerbations.
AB - BACKGROUND: There is no effective way to predict cystic fibrosis (CF) pulmonary
exacerbations (CFPE) before they become symptomatic or to assess satisfactory
treatment responses. METHODS: RNA sequencing of peripheral blood neutrophils from
CF patients before and after therapy for CFPE was used to create transcriptome
profiles. Transcripts with an average transcripts per million (TPM) level > 1.0
and a false discovery rate (FDR) < 0.05 were used in a cosine K-nearest neighbor
(KNN) model. Real time PCR was used to corroborate RNA sequencing expression
differences in both neutrophils and whole blood samples from an independent
cohort of CF patients. Furthermore, sandwich ELISA was conducted to assess plasma
levels of MRP8/14 complexes in CF patients before and after therapy. RESULTS: We
found differential expression of 136 transcripts and 83 isoforms when we compared
neutrophils from CF patients before and after therapy (>1.5 fold change, FDR
adjusted P < 0.05). The model was able to successfully separate CF flare samples
from those taken from the same patients in convalescence with an accuracy of 0.75
in both the training and testing cohorts. Six differently expressed genes were
confirmed by real time PCR using both isolated neutrophils and whole blood from
an independent cohort of CF patients before and after therapy, even though levels
of myeloid related protein MRP8/14 dimers in plasma of CF patients were
essentially unchanged by therapy. CONCLUSIONS: Our findings demonstrate the
potential of machine learning approaches for classifying disease states and thus
developing sensitive biomarkers that can be used to monitor pulmonary disease
activity in CF.
PMID- 29941319
TI - Electrochemical measurement of membrane cholesterol correlates with CFTR function
and is HDAC6-dependent.
AB - BACKGROUND: Previous studies have demonstrated that CF epithelial cells exhibit
increased cholesterol content at the plasma membrane compared to wild type
controls as measured by electrochemical methods. Microtubule dysregulation that
impacts intracellular transport has also been identified in CF cells and is
reversible with histone deacetylase 6 (HDAC6) inhibition, a regulator of tubulin
acetylation. The hypothesis of this study is that increased membrane cholesterol
content in CF cells is dependent on HDAC6 regulation. METHODS: Electrochemical
measurement of membrane cholesterol in mouse trachea and in primary human CF
bronchial epithelial cells is used to monitor CFTR correction and manipulation of
cholesterol processing by HDAC6 inhibition. RESULTS: Data demonstrate that
induction of Cftr expression in an inducible CF mouse model restores tubulin
acetylation levels and normalizes membrane cholesterol content. To test the
relationship between tubulin acetylation, membrane cholesterol levels were
measured in a CF mouse model depleted of Hdac6 expression (CF/HDA). CF/HDA mouse
trachea have WT membrane cholesterol levels while CF mice have approximately two
fold increase in membrane cholesterol compared to WT consistent with previous
studies. Pharmacological inhibition of HDAC6 in primary human CF bronchial
epithelial cells also reduces membrane cholesterol levels. CONCLUSIONS: This
study demonstrates that elevated membrane cholesterol in CF epithelium is
regulated by HDAC6 function and that the electrochemical measure of membrane
cholesterol correlates with both genetic and pharmacological CFTR correction.
PMID- 29941320
TI - Managing unplanned severe opiate withdrawal after Vivitrol.
PMID- 29941321
TI - Comparison of acute management of atrial fibrillation in heart failure with
unequal sized groups.
PMID- 29941322
TI - The effect of angioembolization for life-threatening retroperitoneal hemorrhage
in patients with pelvic fracture.
AB - BACKGROUND: Conventionally, pelvic fracture-related acute retroperitoneal
hemorrhage (ARH) is life threatening and difficult to control. However, the use
of angioembolization to treat fracture-associated ARH improves the hemodynamic
stability of patients with pelvic fractures. The role of angioembolization in the
management of patients with pelvic fracture-related ARH was examined. MATERIALS
AND METHODS: We retrospectively reviewed a large case series of patients with
pelvic fractures between January 2010 and December 2014. Comparisons were made
between patients with and without ARH. In addition, the characteristics of
mortality were delineated, whereas the causes of death in patients with pelvic
fracture were discussed and analyzed. RESULTS: A total of 1070 patient records
were reviewed during the 60-month study period, and the overall mortality rate of
pelvic fracture was 7.7% (82/1070). However, there were only seven patients who
died due to uncontrolled ARH (0.7%). The patients with ARH had more injuries to
other organs than did the patients without ARH (head: 79.7% vs. 31.7%, p < 0.001;
chest: 50.3% vs. 10.9%, p < 0.001; abdomen: 72.0% vs. 22.7%, p < 0.001; spine:
12.6% vs. 4.4%, p < 0.001; extremities: 69.2% vs. 44.3%, p < 0.001). CONCLUSION:
The treatment for pelvic fracture patients declared dead upon arrival remains
limited. However, pelvic fracture-related ARH could be controlled effectively
with angioembolization. In addition to ARH, injuries to other organs may play a
key role in the mortality of patients with pelvic fractures.
PMID- 29941323
TI - The authors respond "Metoprolol vs. diltiazem in the acute management of atrial
fibrillation in patients with heart failure with reduced ejection fraction".
PMID- 29941324
TI - HLA-DR is aberrantly expressed at feto-maternal interface in pre-eclampsia.
AB - In normal pregnancy, villous cytotrophoblast and syncytiotrophoblast do not
express HLA Class I and Class II molecules, while invasive extravillous
trophoblast only express class I HLA-C and the atypical class Ib antigens, HLA-G,
-E and -F. Inadequate maternal tolerance of invasive trophoblast has been
proposed as a possible immunologic trigger of poor trophoblast invasion and
subsequent occurrence of pre-eclampsia. This study aimed to investigate possible
aberrant expression of class II HLA-DR on placentae and syncytiotrophoblast
derived extracellular vesicles (STEVs), obtained by dual placental perfusion,
from pre-eclampsia (n = 23) and normal pregnant (n = 14) women. Here we
demonstrate that HLA-DR can be detected in syncytiotrophoblast from a significant
proportion of pre-eclampsia but not control placentae. HLA-DR was also observed,
by flow cytometry, on STEVs and associated with placental alkaline phosphatase to
validate their placental origin. HLA-DR positive syncytiotrophoblast was detected
in placental biopsies from pre-eclampsia but not normal control cases, using
immunohistochemistry. The HLA may be fetal or maternal origin. In the latter case
a possible mechanism of acquisition is trogocytosis.
PMID- 29941325
TI - Characterisation of putative immunomodulatory gene knockouts of lumpy skin
disease virus in cattle towards an improved vaccine.
AB - Lumpy skin disease virus (LSDV) is responsible for causing severe economic losses
to cattle farmers throughout Africa, the Middle East, and more recently, South
Eastern Europe and Russia. It belongs to the Capripoxvirus genus of the
Poxviridae family, with closely related sheeppox and goatpox viruses. Like other
poxviruses, the viral genome codes for a number of genes with putative
immunomodulatory capabilities. Current vaccines for protecting cattle against
lumpy skin disease (LSD) based on live-attenuated strains of field isolates
passaged by cell culture, resulting in random mutations. Although generally
effective, these vaccines can have drawbacks, including injection site reactions
and/or limited immunogenicity. A pilot study was conducted using a more targeted
approach where two putative immunomodulatory genes were deleted separately from
the genome of a virulent LSDV field isolate. These were open reading frame (ORF)
005 and ORF008, coding for homologues of an interleukin 10-like and interferon
gamma receptor-like gene, respectively. The resulting knockout constructs were
evaluated in cattle for safety, immunogenicity and protection. Severe post
vaccinal reactions and febrile responses were observed for both constructs. Two
calves inoculated with the ORF008 knockout construct developed multiple lesions
and were euthanised. Following challenge, none of the animals inoculated with the
knockout constructs showed any external clinical signs of LSD, compared to the
negative controls. Improved cellular and humoral immune responses were recorded
in both of these groups compared to the positive control. The results indicate
that at the high inoculation doses used, the degree of attenuation achieved was
insufficient for further use in cattle due to the adverse reactions observed.
PMID- 29941327
TI - Potential impact of maternal vaccination on life-threatening respiratory
syncytial virus infection during infancy.
AB - BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of
infant mortality. Here, we estimated the potential impact of maternal vaccination
against RSV on life-threatening RSV infection in infants. METHODS: We developed a
mathematical model for maternal vaccine-induced antibody dynamics and used
characteristics of a maternal RSV vaccine currently in phase 3 of clinical
development. The model was applied to data from two cohorts of children younger
than 12 months with RSV-related paediatric intensive care unit (PICU) admission
in the United Kingdom (n = 370) and the Netherlands (n = 167), and a cohort of
211 children younger than 12 months with RSV-related in-hospital death from 20
countries worldwide. RESULTS: Our model predicted that, depending on vaccine
efficiency, maternal vaccination at 30 weeks' gestational age could have
prevented 62-75% of RSV-related PICU admissions in the United Kingdom and 76-87%
in the Netherlands. For the global mortality cohort, the model predicted that
maternal vaccination could have prevented 29-48% of RSV-related in-hospital
deaths. Preterm children and children with comorbidities were predicted to
benefit less than (healthy) term children. CONCLUSIONS: Maternal vaccination
against RSV may substantially decrease life-threatening RSV infections in
infants.
PMID- 29941328
TI - The possible contemporary presence of BRONJ and oral squamous cell carcinoma.
PMID- 29941326
TI - Declining responsiveness to influenza vaccination with progression of human
pregnancy.
AB - BACKGROUND: Influenza immunization is universally recommended during pregnancy to
protect mothers and their offspring. However, pregnancy-induced shifts in vaccine
responsiveness remain poorly defined. METHODS: Quantitative and qualitative
shifts in the serological response to influenza vaccination were evaluated in
healthy women throughout the course of pregnancy. Serum was obtained before and
after vaccination among 71 pregnant and 67 non-pregnant women during the 2011-12
and 2012-13 influenza seasons. Serum hemagglutination inhibition (HAI) assay was
used to investigate anti-influenza antibody responses by comparing pre-vaccine
and post-vaccine geometric mean titers (GMTs) between groups for each antigen.
IgG1, IgG2, IgG3, and IgG4 anti-influenza titers were also evaluated by enzyme
linked immunosorbent assay (ELISA). Pregnancy induced shifts in HAI titers and
levels of each anti-influenza antibody isotype were evaluated using linear
regression models. RESULTS: Post-vaccine GMTs at day 28 were significantly
reduced for women vaccinated during pregnancy for A/California (H1N1) in 2011 (p
= 0.027), A/Perth (H3N2) in 2011 (p = 0.037), and B/Wisconsin in 2012 (p =
0.039). Vaccine responses progressively declined with the initiation of
vaccination later in pregnancy. Anti-H1N1 IgG1, IgG2, and IgG3 titers were
reduced in pregnant women compared to non-pregnant controls, and these titers
declined with pregnancy progression. The most striking differences were found for
anti-H1N1 IgG1, where titers decreased by approximately 7% each week throughout
pregnancy. CONCLUSIONS: HAI responses elicited by immunization were significantly
reduced during pregnancy for three different influenza vaccine antigens. Anti
H1N1 IgG1 was significantly lower in pregnant women and decreased throughout the
course of pregnancy. Waning serological responsiveness to influenza vaccination
with the progression of human pregnancy has important translational implications
for when immunization should be optimally administered during pregnancy.
PMID- 29941329
TI - Letter to the editor: "Utility of PET-CT in detecting nodal metastasis in cN0
early stage oral cavity squamous cell carcinoma".
PMID- 29941331
TI - Examining the use of allopurinol: Perspectives from recent drug injury relief
applications.
AB - BACKGROUND/PURPOSE: Previous studies have reported that the indication and
starting dose of allopurinol may be associated with the incidence of
hypersensitive reactions. As allopurinol-related severe cutaneous adverse
reactions (SCARs) constitute a significant proportion of drug injury relief
applications in Taiwan, this study sought to examine allopurinol use and related
adverse reactions through an analysis of recent drug injury relief applications.
METHODS: Allopurinol-related drug injury relief applications from 1999 to 2016
were collected, and descriptive statistical methods were used to analyze recent
applications dating from 2011 to 2016. RESULTS: A total of 174 allopurinol
related drug injury relief applications were submitted between 2011 and 2016,
with the majority involving cases over the age of 65 (75.3%; mean age of all
cases was 69.2). Most allopurinol-related drug injuries concerned the skin (173
out of 174 cases, 99.4%). The majority of cases had other co-morbidities such as
cardiovascular disease/hypertension (86.2%), chronic kidney disease (58.6%), or
diabetes (46.6%). Over 70% of cases initiated allopurinol at a dose of 100 mg/day
or less. Analysis revealed that the greatest number of cases (44.6%) occurred in
those with an estimated glomerular filtration rate (eGFR) between 15 and 60
mL/min/1.73 m2 and who initiated allopurinol at a dose of 100 mg/day. CONCLUSION:
Old age and renal dysfunction are key risk factors for allopurinol
hypersensitivity. When considering allopurinol for elderly patients with impaired
kidney function, a full risk-benefit assessment, dosage adjustments, and careful
monitoring may be warranted.
PMID- 29941330
TI - Intelligent system to predict intradialytic hypotension in chronic hemodialysis.
AB - BACKGROUND: Intradialytic hypotension (IDH) is a serious complication and a major
risk factor of increased mortality during hemodialysis (HD). However, predicting
the occurrence of intradialytic blood pressure (BP) fluctuations clinically is
difficult. This study aimed to develop an intelligent system with capability of
predicting IDH. METHODS: In developing and training the prediction models in the
intelligent system, we used a database of 653 HD outpatients who underwent 55,516
HD treatment sessions, resulting in 285,705 valid BP records. We built models to
predict IDH at the next BP check by applying time-dependent logistic regression
analyses. RESULTS: Our results showed the sensitivity of 86% and specificity of
81% for both nadir systolic BP (SBP) of <90 mmHg and <100 mmHg, suggesting good
performance of our prediction models. We obtained similar results in validating
via test data and data of newly enrolled patients (new-patient data), which is
important for simulating prospective situations wherein dialysis staff are
unfamiliar with new patients. This compensates for the retrospective nature of
the BP records used in our study. CONCLUSION: The use of this validated
intelligent system can identify patients who are at risk of IDH in advance, which
may facilitate well-timed personalized management and intervention.
PMID- 29941332
TI - Learning from the Past While Looking to the Future: Nurses' Continuing Roles as
Advocates in the Era of U=U.
PMID- 29941333
TI - Hepatotoxicity upon using niacin to pass a drug test: A case report.
AB - OBJECTIVES: To report a case of hepatotoxicity when niacin was used by a patient
with HIV to pass a drug test. METHODS: Niacin is a soluble pyridine derivative
widely used in the management of dyslipidemia. Common adverse effects include
flushing, nausea, gastrointestinal discomfort, and hepatotoxicity. The use of
niacin for nonmedical purposes has been increasing in prevalence in recent years,
particularly in attempts to alter or mask results of urine drug tests. Although
there is no scientific evidence that niacin can alter a urine drug screen result,
easily retrievable information exists on the Internet touting niacin as a
potential way to prevent detection of tetrahydrocannabinol (THC). The following
report describes a case of hepatotoxicity in an HIV-infected adult who reported
using niacin to mask THC in urine drug screen results. RESULTS: The patient
developed marked elevations in his liver enzymes (aspartate aminotransferase
greater than 25 times the upper limit of normal and alanine aminotransferase
greater than 3 times the upper limit of normal) that resolved after
discontinuation of the drug. Because of the patient's self-reported use and
discontinuation of niacin, the Naranjo Adverse Drug Reaction Probability Scale
demonstrated a "definite" relationship between the development of hepatotoxicity
and the ingestion of over-the-counter sustained-release niacin. The patient did
not develop further clinical abnormalities proposed to be secondary to niacin
toxicity in previously published case reports, including glucose abnormalities,
coagulopathies, metabolic acidosis, QTc prolongation, and myalgias. CONCLUSION:
Health care providers should be aware of this nonmedical use of niacin to alter
or mask a drug test, especially when discerning the cause of hepatotoxicity. In
addition, pharmacists in the community setting should be aware of this use of
niacin when encountering patients purchasing over-the-counter niacin,
particularly in patients who may be more likely to use illicit substances.
PMID- 29941334
TI - Detection of bovine viral diarrhoea virus nucleic acid, but not infectious virus,
in bovine serum used for human vaccine manufacture.
AB - Bovine viral diarrhoea virus (BVDV) is a cattle pathogen that has previously been
reported to be present in bovine raw materials used in the manufacture of
biological products for human use. Seven lots of trivalent measles, mumps and
rubella (MMR) vaccine and 1 lot of measles vaccine from the same manufacturer,
together with 17 lots of foetal bovine serum (FBS) from different vendors, 4 lots
of horse serum, 2 lots of bovine trypsin and 5 lots of porcine trypsin were
analysed for BVDV using recently developed techniques, including PCR assays for
BVDV detection, a qRT-PCR and immunofluorescence-based virus replication assays,
and deep sequencing to identify and genotype BVDV genomes. All FBS lots and one
lot of bovine-derived trypsin were PCR-positive for the presence of BVDV genome;
in contrast all vaccine lots and the other samples were negative. qRT-PCR based
virus replication assay and immunofluorescence-based infection assay detected no
infectious BVDV in the PCR-positive samples. Complete BVDV genomes were generated
from FBS samples by deep sequencing, and all were BVDV type 1. These data
confirmed that BVDV nucleic acid may be present in bovine-derived raw materials,
but no infectious virus or genomic RNA was detected in the final vaccine
products.
PMID- 29941335
TI - WITHDRAWN: Establishment of the first International Standard for human anti
typhoid capsular Vi polysaccharide IgG.
PMID- 29941336
TI - Evaluation of broad-spectrum beta-lactam prescriptions (except carbapenems) in a
French teaching hospital.
AB - OBJECTIVES: We aimed to assess broad-spectrum beta-lactam prescriptions (except
carbapenems) in a French teaching hospital and the impact of controlled
dispensing, antimicrobial management team, and antibiotic treatment reassessment
on Day 2-3. PATIENTS AND METHODS: We performed a point-prevalence study in all
hospital units and analyzed curative antibiotic broad-spectrum beta-lactam
prescriptions. The assessment focused on indication, dosing, combinations,
revaluation on Day 2-3, and treatment duration. RESULTS: Sixty-seven broad
spectrum beta-lactam prescriptions were identified. The main prescriptions were
amoxicillin-clavulanic acid (37%, n=25), ceftriaxone (36%, n=24), and
piperacillin-tazobactam (16%, n=11). Indications, doses, combinations, and
reassessment on Day 2-3 were appropriate, respectively 90% (n=60), 96% (n=64),
94% (33/35 combinations), and 88% (n=59). However, appropriate treatment
durations amounted to only 63% (n=42). The benefit of controlled dispensing was
observed in terms of overall antibiotic treatment duration: 86% versus 51%
adequacy for uncontrolled dispensing of beta-lactams (P=0.02). The antimicrobial
management team improved the antibiotic treatment duration: 73% of appropriate
durations versus 44% for beta-lactams not monitored by the team, but this
difference was not significant. CONCLUSION: Broad-spectrum beta-lactams were
usually well prescribed but the adequacy of treatment duration could be improved,
especially by reinforcing the monitoring of prescriptions.
PMID- 29941337
TI - [How I do... a lumpectomy with the round-block oncoplasty technique?]
PMID- 29941338
TI - [Evolution of clinical practices in the surgical management of pelvic organ
prolapse in a "vaginalist" team over the period 2010-2015: A paradigm shift
towards pluripotency].
AB - OBJECTIVES: To determine whether the 2011 FDA alert and French Guidelines have
impacted the routine surgical practice in the management of pelvic organ prolapse
in a "vaginalist" team over the period 2010-2015. METHODS: Retrospective study
involving all patients undergoing surgical management of anterior and/or apical
symptomatic pelvic organ prolapse during the civil years 2010 and 2015. Both
naive and relapsed prolapses were eligible. RESULTS: Overall, 338 patients were
included: 187 in 2010 and 151 in 2015. Among patients with naive prolapse, we
observed a significant increase in the number of laparoscopic sacrocolpopexies
(11.1% in 2010 versus 34.4% in 2015, P=0.001) and a significant decline in the
use of native tissue repair (67.6% in 2010 versus 39% in 2015, P=0.001). While
the number of transvaginal meshes did not decline over the study period, their
indications displayed a significant evolution towards a restricted use to
advanced stages. We did not observe any difference regarding the treatment of
recurred pelvic organ prolapse. Vaginal route remained the preferred approach in
this indication. CONCLUSION: In our "vaginalist" team, routine practice has
significantly evolved over the period 2010-2015, resulting in a diversification
of the healthcare offer. This paradigm shift towards pluripotency is mandatory,
since patients' preference should also drive the choice of both surgical route
and technique.
PMID- 29941339
TI - Selective biopsy of the sentinel node in cancer of cervix: Experience in
validation phase.
AB - BACKGROUND AND OBJECTIVE: Sentinel lymph node biopsy (SLNB) was created to reduce
the morbidity associated with pelvic lymphadenectomy in the early stages of
cervical cancer (CC), preserving its prognostic information. The goal is to
assess the diagnostic validity of SLNB in CC in initial stages (IA1 with
lymphovascular infiltration (LVI) +, IA2, IB1 and IIA1), thus avoiding
unnecessary lymphadenectomies in many of the cases. MATERIAL AND METHOD: From
January 2012 to April 2017, 23 patients with initial stages of CC were included
in a cross-sectional study to evaluate the effectiveness of the SLNB in CC with a
mixed technique of cervical injection of 99mTc-nanocolloid of albumin and
methylene blue, using combined planar lymphoscintigraphy with multimodality
SPECT/CT image and subsequent removal of the sentinel node (SN) by laparoscopy.
RESULTS: The detection rate of SLNB with the mixed technique was 95.65%, with a
negative predictive value (NPV) of 95.45% and sensitivity (S) of 100% in the case
of bilateral drainage. The mean of excised SN was 3 (range 1-5). The bilateral
detection rate in laparoscopy was 85.35%. The concordance between SPECT/CT and
laparoscopy for the number and bilaterality of the SN using the Pearson
coefficient was r = 0.727 and r = 0.833, respectively; p = 0.01. We only found
one SN with a deferred result of micrometastasis and one false negative was
detected. CONCLUSIONS: SLNB in CC using a mixed technique has a high detection
and bilateral drainage rate, but S is still low if we include cases of unilateral
drainage. A greater number of cases and the development of intraoperative
ultrastaging could increase the S of the technique and to reduce the number of
false negatives.
PMID- 29941340
TI - Fatty Acid Metabolism is Associated With Disease Severity After H7N9 Infection.
AB - BACKGROUND: Human infections with the H7N9 virus could lead to lung damage and
even multiple organ failure, which is closely associated with a high mortality
rate. However, the metabolic basis of such systemic alterations remains unknown.
METHODS: This study included hospitalized patients (n = 4) with laboratory
confirmed H7N9 infection, healthy controls (n = 9), and two disease control
groups comprising patients with pneumonia (n = 9) and patients with pneumonia who
received steroid treatment (n = 10). One H7N9-infected patient underwent lung
biopsy for histopathological analysis and expression analysis of genes associated
with lung homeostasis. H7N9-induced systemic alterations were investigated using
metabolomic analysis of sera collected from the four patients by using ultra
performance liquid chromatography-mass spectrometry. Chest digital radiography
and laboratory tests were also conducted. FINDINGS: Two of the four patients did
not survive the clinical treatments with antiviral medication, steroids, and
oxygen therapy. Biopsy revealed disrupted expression of genes associated with
lung epithelial integrity. Histopathological analysis demonstrated severe lung
inflammation after H7N9 infection. Metabolomic analysis indicated that fatty acid
metabolism may be inhibited during H7N9 infection. Serum levels of palmitic acid,
erucic acid, and phytal may negatively correlate with the extent of lung
inflammation after H7N9 infection. The changes in fatty acid levels may not be
due to steroid treatment or pneumonia. INTERPRETATION: Altered structural and
secretory properties of the lung epithelium may be associated with the severity
of H7N9-infection-induced lung disease. Moreover, fatty acid metabolism level may
predict a fatal outcome after H7N9 virus infection.
PMID- 29941341
TI - Gefitinib and Methotrexate to Treat Ectopic Pregnancies with a Pre-Treatment
Serum hCG 1000-10,000 IU/L: Phase II Open Label, Single Arm Multi-Centre Trial.
AB - BACKGROUND: Ectopic pregnancies are a leading cause of maternal mortality. Most
are treated surgically. We evaluated the efficacy and safety of combining oral
gefitinib (epidermal growth factor receptor inhibitor) with methotrexate to treat
larger ectopic pregnancies. METHODS: We performed a phase II, single arm, open
label study across four hospitals in Edinburgh and Melbourne. We recruited women
with a stable tubal ectopic pregnancy and a pre-treatment serum hCG between 1000
and 10,000 IU/L. We administered intramuscular methotrexate (50 mg/m2) once, and
oral gefitinib (250 mg) for seven days. The primary outcome was the percentage
successfully treated without needing surgery. To show the treatment is at least
70% effective, 28 participants were required, and 24 or more successfully treated
without surgery. Secondary outcomes were safety, tolerability, and time to
resolution. This study is registered (ACTRN12611001056987). FINDINGS: 30
participants with stable tubal ectopic pregnancies were recruited but two
withdrew, leaving 28 participants. The median (+/- range) pre-treatment serum hCG
was 2039 (1031-8575) IU/L and nine had pre-treatment hCGs levels >3000 IU/L. The
treatment successfully resolved 86% (24/28) cases with a median (+/-range) time
to resolution of 32 (18-67) days. The treatment caused transient rash and
diarrhoea, but no serious adverse events. INTERPRETATION: Combination gefitinib
and methotrexate is at least 70% effective in resolving ectopic pregnancies with
a pre-treatment serum hCG 1000-10,000 IU/L. This may be a new way to treat most
stable ectopic pregnancies, but needs to be validated via a randomised clinical
trial.
PMID- 29941342
TI - Initial Identification of a Blood-Based Chromosome Conformation Signature for
Aiding in the Diagnosis of Amyotrophic Lateral Sclerosis.
AB - BACKGROUND: The identification of blood-based biomarkers specific to the
diagnosis of amyotrophic lateral sclerosis (ALS) is an active field of academic
and clinical research. While inheritance studies have advanced the field, a
majority of patients do not have a known genetic link to the disease, making
direct sequence-based genetic testing for ALS difficult. The ability to detect
biofluid-based epigenetic changes in ALS would expand the relevance of using
genomic information for disease diagnosis. METHODS: Assessing differences in
chromosomal conformations (i.e. how they are positioned in 3-dimensions)
represents one approach for assessing epigenetic changes. In this study, we used
an industrial platform, EpiSwitchTM, to compare the genomic architecture of
healthy and diseased patient samples (blood and tissue) to discover a chromosomal
conformation signature (CCS) with diagnostic potential in ALS. A three-step
biomarker selection process yielded a distinct CCS for ALS, comprised of
conformation changes in eight genomic loci and detectable in blood. FINDINGS: We
applied the ALS CCS to determine a diagnosis for 74 unblinded patient samples and
subsequently conducted a blinded diagnostic study of 16 samples. Sensitivity and
specificity for ALS detection in the 74 unblinded patient samples were 83?33% (CI
51?59 to 97?91%) and 76?92% (46?19 to 94?96%), respectively. In the blinded
cohort, sensitivity reached 87?50% (CI 47?35 to 99?68%) and specificity was 75?0%
(34?91 to 96?81%). INTERPRETATIONS: The sensitivity and specificity values
achieved using the ALS CCS identified and validated in this study provide an
indication that the detection of chromosome conformation signatures is a
promising approach to disease diagnosis and can potentially augment current
strategies for diagnosing ALS. FUND: This research was funded by Oxford
BioDynamics and Innovate UK. Work in the Oxford MND Care and Research Centre is
supported by grants from the Motor Neurone Disease Association and the Medical
Research Council. Additional support was provided by the Northeast ALS Consortium
(NEALS).
PMID- 29941343
TI - Somatic FGFR3 Mutations Distinguish a Subgroup of Muscle-Invasive Bladder Cancers
with Response to Neoadjuvant Chemotherapy.
AB - The administration of neoadjuvant chemotherapy (NAC) preceding radical cystectomy
benefits overall survival for patients with muscle-invasive bladder cancer
(MIBC). However, the relationship between the genetic profiling of MIBC and NAC
response remains unclear. Here, a mutation panel of six cancer-associated genes
(TSC1, FGFR3, TERT, TP53, PIK3CA and ERBB2) and an immunohistochemistry (IHC)
panel containing eight bladder cancer (BC) biomarkers (EGFR, RRM1, PD-L1, BRCA1,
TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin alpha3beta1 (AG) and CK5/6)
were developed. BC samples from patients who showed a pathologic response (n =
39) and non-response (n = 13) were applied to the panel analysis. ERBB2, FGFR3
and PIK3CA exclusively altered in the responders group (19/39, 48.7%), in which
FGFR3 mutations were significantly enriched in patients with a response in the
cohort (14/39, 35.9%; P = 0.01). Additionally, strong expression of ERCC1 was
associated with a pathologic response (P = 0.01). However, positive lymph node
metastasis (P < 0.01) and lymph-vascular invasion (LVI) (P = 0.03) were
correlated with a non-response. Overall, the data show that FGFR3 mutations and
elevated expression of ERCC1 in MIBCs are potential predictive biomarkers of the
response to NAC.
PMID- 29941344
TI - Orthostatic Hypotension in the Elderly: A Marker of Clinical Frailty?
AB - BACKGROUND: Orthostatic hypotension (OH) has high prevalence in frail older
adults. However, its effect on mortality, disability, and hospitalization in
frail older adults is poorly investigated. Thus, we assessed the relationship
between the prevalence of OH and its effect on mortality, disability, and
hospitalization in noninstitutionalized older adults stratified by frailty
degree. METHODS: Prospective, observational study of 510 older participants (>=65
years of age) consecutively admitted to a geriatric evaluation unit to perform a
geriatric comprehensive assessment. MEASUREMENTS: Clinical frailty was assessed
using the Italian frailty index (40 items). Systolic blood pressure (mm Hg),
diastolic blood pressure (mm Hg), and heart rate (bpm) were evaluated in
clinostatic position and after 1, 3, and 5 minutes of orthostatic position. OH
was defined with a decrease of 20 mm Hg in systolic blood pressure and/or a
decrease of 10 mm Hg in diastolic blood pressure. RESULTS: OH prevalence was 22%,
and it increased from 9.0% to 66.0% according to frailty degree (P for trend
<.001). When stratified by frailty degree, mortality, disability, and
hospitalization increased from 1.0% to 24.5%, from 39.0% to 77.0% and from 14.0%
to 32.0% in the absence, and from 0.0% to 35.5%, from 42.0% to 95.5% and from
19.0% to 65.5% in the presence of OH, respectively (P < .01 vs absence of OH).
Multivariate analysis showed that the Italian frailty index is more predictive of
mortality, disability, and hospitalization in the presence than in the absence of
OH. CONCLUSIONS: OH is a common condition in frail older adults, and it is
strongly associated with mortality, disability, and hospitalization in the
highest frailty degree. Thus, OH may represent a new marker of clinical frailty.
PMID- 29941345
TI - Combined intracavitary and interstitial brachytherapy of cervical cancer using
the novel hybrid applicator Venezia: Clinical feasibility and initial results.
AB - PURPOSE: To report on first-in-human experience and the initial clinical results
using the hybrid applicator Venezia (Elekta, Sweden) in the treatment of patients
with locally advanced cervical cancer. MATERIAL AND METHODS: Between March, 2017,
and February, 2018, a total of 40 fractions were performed on patients undergoing
definitive chemoradiation and brachytherapy (BT) for cervical cancer. A plan
comparison was conducted evaluating the hybrid applicator with the clinically
used intracavitary and interstitial (IC/IS) BT against a standard plan prescribed
to Point A and a manually optimized plan using only intracavitary (IC) BT.
Overall 80 treatment plans were retrospectively generated. RESULTS: The clinical
use of the hybrid applicator system proved to be feasible in all 40 treatment
fractions. The applicator consists of the IC tandem and two lunar-shaped ovoids
forming a ring that serves as a template for defined parallel and oblique (12
degrees ) needle insertion. MRI preplanning was performed the day before the
implant. One to six needles were placed per fraction, and overall a total of 66
needles were used. No complications such as bleeding or organ penetration
occurred due to needle placement. Significant differences in IC/IS, Point A, and
IC plans were derived for dose application to the target volume; D90 high-risk
clinical target volume was 90.7 vs. 88.1 vs. 80.8 Gy (p = 0.008). Likewise,
sparing of organs at risk differed significantly for bladder D2cc 79.4 vs. 91.8
vs. 79.2 Gy (p = 0.03) and rectum D2cc 58.7 vs. 67.3 vs. 62.5 Gy (p = 0.03).
CONCLUSION: The clinical application of the Venezia applicator is feasible and
allows significantly improved dose coverage while at the same time sufficiently
sparing organs at risk.
PMID- 29941346
TI - Pochoniolides A and B, new antioxidants from the fungal strain Pochonia
chlamydosporia var. spinulospora FKI-7537.
AB - New natural products, designated pochoniolides A and B, were isolated from the
cultured broth of fungal strain FKI-7537 using a physicochemical screening
methodology. Strain FKI-7537 was isolated from a soil sample collected at
Niijima, Tokyo, Japan and identified as Pochonia chlamydosporia var. spinulospora
by morphological characteristics and DNA sequence analysis. The chemical
structures of pochoniolides A and B were elucidated by NMR and mass spectra and
found to be new compounds consisting of a muconolactone moiety connected with a
chromone unit. Pochoniolides A and B were identified as racemate mixtures using
data on optical rotation and circular dichroism spectra. Furthermore, enantiomers
of pochoniolide B, pochoniolides B1 and B2, were separated using a chiral HPLC
column. Pochoniolides A and B showed hydroxyl radical-scavenging and singlet
oxygen-quenching activities.
PMID- 29941347
TI - Comparison of scrotal antegrade sclerotherapy and laparoscopic Palomo surgery in
treatment of adolescent varicocele: A 15-year review.
AB - INTRODUCTION/OBJECTIVE: Varicocele is a common condition seen in adolescence and
associated with adult subfertility. Numerous types of intervention have been
described with differences in success and complication rates. This study aims to
review and compare the surgical outcomes of laparoscopic Palomo surgery and
scrotal antegrade sclerotherapy at our center. STUDY DESIGN: A retrospective
analysis was done of all patients younger than 18 years old with idiopathic
varicocele treated operatively between February 2001 and December 2016.
Demographics such as age at operation, side, varicocele grade, operative date,
and types of operation were collected. Primary outcomes were clinical recurrence,
defined as any grading noted on follow-up within 1 year post-op and post
operative hydrocele. Secondary outcomes were operative time, length of stay, and
other surgical complications. Mann-Whitney U test, independent t test and chi
square tests were used for analysis. All p-values were two-sided and considered
statistically significant at p <= 0.05. RESULTS: A total of 119 patients fit the
criteria, of whom 117 patients were included in data analysis (Table). Sixty-two
patients had laparoscopic Palomo surgery (LPS) and 55 had scrotal antegrade
sclerotherapy (SAS). Clinical recurrence (grade 2-3) within 1 year was similar
between the two groups, with four out of 48 patients in the SAS group and six out
of 62 patients in the LPS group (8.4% in SAS vs. 9.7% in LPS, p = 1.00). Of the
11 patients who had recurrence in the SAS group, seven had grade 1 recurrence
(14.5%), two (4.2%) had grade 2 recurrence, and two (4.2%) had grade 3
recurrence. For the LPS group, 17 out of 62 patients had clinical recurrence
within 1 year, of whom 11 (17.7%) had grade 1 recurrence, one (1.6%) had grade 2,
and five (8.1%) had grade 3 recurrence. Post-operative hydrocele was
significantly higher in the LPS group; there was none in the SAS group but 11
patients in the LPS group (0% in SAS vs. 17.7%, p = 0.002). Three patients had
clinically significant hydrocele requiring Jaboulays' procedure. Complications
other than hydrocele were noted in three patients in the SAS group and one
patient in the LPS group (5.5% in SAS vs. 1.6% in LPS, p = 0.158). None required
operative intervention. No conversion to open procedure was seen in the LPS group
and there were no perioperative complications. Mean operative time was 62.9 min
in the SAS group and 60.7 min in the LPS group (p = 0.624). Mean length of stay
was 17.5 h in the SAS group and 31.7 h in the LPS group (p < 0.001). CONCLUSION:
Both SAS and LPS are safe procedures for treatment of adolescent varicocele with
similar clinical recurrence rate within 1 year. SAS has a significantly lower
rate of post-operative hydrocele.
PMID- 29941348
TI - The intravesical phallus in patients with cloacal exstrophy: An embryologic
conundrum.
AB - BACKGROUND: Phalluses present inside the extrophied bladder of cloacal exstrophy
(CE) newborns have been sporadically reported in the literature; this clinical
entity has largely unknown origins and may represent an extremely rare anomaly of
CE. OBJECTIVE: Along with nearly doubling the number of reported intravesical
phalluses in the literature, this study aims to outline the common anatomic
features and discuss the implications for theories of CE embryogenesis. STUDY
DESIGN: The authors retrospectively identified patients with CE and a potential
intravesical phallus between 1997 and 2017 at two high-volume centers.
Information was obtained about karyotype, age at closure, neurologic and renal
anomalies, diastasis, phallus anatomy, and phallus biopsy pathology. RESULTS: Six
genotypic males met the inclusion criteria. Five of six had a diastasis greater
than 6 cm. Four of six had paired corporal bodies in the intravesical phallus,
one had a single corporal body, and one had a corporal-like structure. Five of
six patients had a phallus located midline in the caudal aspect of the bladder;
one was located midline in the bladder dome. Phallic biopsies were obtained in
three of six patients. Two showed glanular and corporal tissue while the other
showed vascular proliferation morphologically similar to that of erectile tissue.
DISCUSSION: Previous reports suggested that a superior vesicle fissure
configuration, fusion of the corporal bodies, and fused bladder plates were
common findings with an intravesical phallus. With the addition of new cases, the
only consistent variable between patients is a phallus located anywhere along the
bladder plate that can comprise a corporal-like structure, a single corporal
body, or fused corporal bodies. These findings have implications for several
embryologic theories. Although this is a retrospective review with a limited
number of patients, the condition is exceedingly infrequent making it only
observable retrospectively over decades at high volume centers. CONCLUSIONS: The
study outlined common anatomic features of the intravesical phallus in cloacal
exstrophy and discussed the subsequent embryologic implications. In cloacal
exstrophy newborns with presumed aphallia, meticulous inspection of the bladder
plate and biopsy of any potential phallic structures can prevent resection of
phallic tissue.
PMID- 29941349
TI - Post-curing in dental resin-based composites.
AB - OBJECTIVE: To determine the post-curing in six commercial contemporary resin
based composites (RBCs) using axial shrinkage, the degree of conversion, and
Vickers hardness. METHODS: Five Bulk Fill and one conventional RBCs from three
companies were selected with a wide range of filler volume content. The axial
shrinkage of samples that were 1.00mm thick by 9-10mm diameter was measured using
a modified bonded disk method over a time between 15h and 19h at temperatures of
26 degrees C and 34 degrees C (mouth temperature). The degree of conversion (DC)
was collected continuously for 10min using mid-infrared spectroscopy in the
attenuated total reflectance geometry. Vickers hardness was measured at 1h post
irradiation using a load of 300gf. For all three tests, the samples were
irradiated at five exposure times, 20, 5, 3, 1.5 and 1s with a light curing unit
radiant exitance of 1.1W/cm2. Three samples (n=3) were used for each experimental
condition. RESULTS: After light exposure, the axial shrinkage and degree of
conversion exhibited a functional time dependence that was proportional to the
logarithm of time. This suggests an out-of-equilibrium polymer composite glass
that is transitioning to thermal equilibrium. At a sufficiently long time and
among the RBCs investigated, the shrinkage related physical aging rate was found
to vary between 1.34 and 2.00MUm/log(t). The rate was a function of the filler
content. Furthermore, 15h after light exposure, the post-curing shrinkage was
estimated to be an additional 22.5% relative to the shrinkage at 100s for one RBC
at T=34 degrees C. The hardness in the photo-cured RBC was varied by using
different light exposure times. The first two experimental techniques show that
the higher the initial DC 10min after light exposure, the smaller is the post
curing shrinkage related and DC related physical aging rates. A direct
correlation was observed between the shrinkage related and the DC related
physical aging rates. SIGNIFICANCE: Post-curing shrinkage should be evaluated for
longer than 1h. The post-curing shrinkage 15h after light exposure in dental RBCs
can be appreciable. The long-term development of built-in stress within the tooth
wall structure may shorten the restoration's lifespan.
PMID- 29941350
TI - In vitro degradation of a biodegradable polylactic acid/magnesium composite as
potential bone augmentation material in the presence of titanium and PEEK dental
implants.
AB - OBJECTIVE: The aim of this study was to assess the degradation behavior by
measuring the H2 release of a biodegradable composite consisting of a polylactic
acid matrix reinforced with 30% wt. spherical magnesium microparticles (PLA/Mg)
as potential bone augmentation material in combination with dental implants of
either titanium or polyetheretherketone (PEEK) in order to evaluate the potential
influence of the titanium dental implants on the corrosion behavior of the Mg
particles within the PLA matrix. METHODS: Three PEEK dental implants and three
titanium dental implants were put into a central perforation of six PLA/Mg-discs.
These samples were incubated at 37 degrees C for 30days in McCoy's 5A modified
medium and the H2 release was evaluated. RESULTS: Between day 7 and day 16 the
average H2 release per cm2 of the surface of the PLA/Mg-samples in combination
with the titanium implants was significantly higher than that of the sample group
combined with the implants of PEEK (3.1+/-0.4ml vs. 2.8+/-0.4ml). This
significant difference disappeared afterwards, whereas the H2 release was highest
at day 30 and amounted 3.5+/-0.7ml/cm2 for the group with the titanium implants
and 3.2+/-0.8ml/cm2 for the group with the PEEK implants. SIGNIFICANCE: Regarding
the similar values of the degradation depending H2 release of the two implant
material groups, the co-implantation of a PLA/Mg composite is not only possible
with new metal-free implant materials such as PEEK, but also with conventional
implants of titanium.
PMID- 29941351
TI - Correlation of resin viscosity and monomer conversion to filler particle size in
dental composites.
AB - OBJECTIVE: The viscosity of dental resin composites is important in their
formulation and clinical use; it depends on the filler particle size and loading.
We intend to study the viscosity and conversion of composites made of low
dispersity spherical silica fillers. METHODS: Experimental dental resin
composites were formulated using low dispersity spherical silica particles of
graded sizes (75, 150, 500, 350, 500, 1000nm) at several loading levels with
resins based on Bis-GMA and UDMA. Their rheological properties and double bond
conversion were measured with a rheometer and differential scanning calorimeter,
respectively. RESULTS: The complex viscosity of the unpolymerized pastes can be
fit to an extended Krieger-Dougherty equation that includes an adjustment factor
to account for filler particle surface area. This relationship is also extended
to estimate the degree of conversion, where the calculated or experimental
viscosity is used to predict the resulting conversion. SIGNIFICANCE: The enhanced
understanding of the relationship of filler size, composite viscosity, and
monomer conversion will allow improved accuracy in the prediction of the
properties of dental resin composite formulations to obtain ideal viscosity for
their clinical use and a high degree of conversion.
PMID- 29941352
TI - Experimental tricalcium silicate cement induces reparative dentinogenesis.
AB - OBJECTIVES: To overcome shortcomings of hydraulic calcium-silicate cements
(hCSCs), an experimental tricalcium silicate (TCS) cement, named 'TCS 50', was
developed. In vitro research showed that TCS 50 played no negative effect on the
viability and proliferation of human dental pulp cells, and it induced cell
odontogenic differentiation. The objective was to evaluate the pulpal repair
potential of TCS 50 applied onto exposed minipig pulps. METHODS: Twenty permanent
teeth from three minipigs were mechanically exposed and capped using TCS 50; half
of the teeth were scheduled for 7-day and the other half for 70-day examination
(n=10). Commercial hCSCs ProRoot MTA and TheraCal LC were tested as references
(n=8). Tooth discoloration was examined visually. After animal sacrifice, the
teeth were scanned using micro-computed tomography; inflammatory response at day
7 and day 70, mineralized tissue formation at day 70 were assessed
histologically. RESULTS: Up to 70 days, TCS 50 induced no discoloration, ProRoot
MTA generated gray/black discoloration in all teeth. For TCS 50, 40.0% pulps
exhibited a mild/moderate inflammation at day 7. No inflammation was detected and
complete reparative dentin with tubular structures was formed in all pulps after
70 days. ProRoot MTA induced a similar response, TheraCal LC generated a less
favorable response in terms of initial inflammation and reparative dentin
formation; however, these differences were not significant (Chi-square test of
independence: p>0.05). SIGNIFICANCE: TCS 50 induced reparative dentinogenesis in
minipig pulps. It can be considered as a promising pulp-capping agent, also for
aesthetic areas.
PMID- 29941353
TI - Advances in the development of molecular genetic tools for Mycobacterium
tuberculosis.
AB - Mycobacterium tuberculosis, a clinically relevant Gram-positive bacterium of
great clinical relevance, is a lethal pathogen owing to its complex physiological
characteristics and development of drug resistance. Several molecular genetic
tools have been developed in the past few decades to study this microorganism.
These tools have been instrumental in understanding how M. tuberculosis became a
successful pathogen. Advanced molecular genetic tools have played a significant
role in exploring the complex pathways involved in M. tuberculosis pathogenesis.
Here, we review various molecular genetic tools used in the study of M.
tuberculosis. Further, we discuss the applications of clustered regularly
interspaced short palindromic repeat interference (CRISPRi), a novel technology
recently applied in M. tuberculosis research to study target gene functions.
Finally, prospective outcomes of the applications of molecular techniques in the
field of M. tuberculosis genetic research are also discussed.
PMID- 29941354
TI - The 1918 Influenza Pandemic: one hundred years of progress, but where now?
PMID- 29941355
TI - Glucocorticoid-Induced Osteoporosis: Management Challenges in Older Patients.
AB - Glucocorticoid-induced osteoporosis remains the most common type of secondary
osteoporosis, mostly due to use of oral glucocorticoids rather than due to
endogenous overproduction of cortisol. Partly because glucocorticoids are
prescribed by a wide variety of clinicians for many different inflammatory
disorders, only a minority of older individuals have adequate and timely
assessment of their enhanced fracture risk, and fewer are offered treatment.
Assessment should include bone density, the FRAX calculation, and, in many cases,
images of the spine. Glucocorticoids decrease osteoblast function and increase
apoptosis of osteoblasts and osteocytes, leading to increased fracture risk soon
after starting glucocorticoids. Guidelines provide evidence-based recommendations
for evaluation and treatment, but there are differences in extant guidelines, and
methods to improve adherence to the guidelines have mostly failed. A strong case
can be made to use anabolic drugs first in high-risk patients based on
pathophysiology and head-to-head clinical trials.
PMID- 29941356
TI - Esophageal replacement by gastric transposition: A single surgeon's experience
from a tertiary pediatric surgical center.
AB - BACKGROUND: Many pediatric surgeons have limited experience of esophageal
replacement. This study reports outcomes of esophageal replacement by gastric
transposition performed by a single UK-based pediatric surgeon. METHODS:
Consecutive patients were identified who underwent esophageal replacement by
gastric transposition over a 28 year period. Clinical and demographic data were
collected. Weight-for-age Z-scores were calculated for esophageal atresia
patients. RESULTS: Nineteen patients were identified. Indication in the majority
was long-gap esophageal atresia (n = 17; 10 with tracheoesophageal fistula). At
surgery, median age was 8.5 months (range 2-55); median weight was 7.4 kg (range
4.0-17.4 kg). A right-sided thoracotomy or transhiatal approach was used. Median
postoperative length of stay was 17.5 days (range 7-130); median intensive care
stay was three days (range 1-63). There were no deaths. Anastomotic leak rate at
30 days was 10.5% (n = 2). One patient required early stricture dilatation.
Median weight-for-age Z-score increased from -2.17 at one year of age to -1.86,
1.70 and -1.93 at 5, 10 and 15 years. CONCLUSIONS: Esophageal replacement by
gastric transposition offers a potentially life-changing treatment; however, it
is associated with significant morbidity. The majority of patients eventually
achieve full oral feeding and maintenance of weight gain trajectory. A right
sided approach to the esophagus is feasible. TYPE OF STUDY: Treatment Study.
LEVEL OF EVIDENCE: IV.
PMID- 29941357
TI - The Mullerian Black Box: Predicting and defining Mullerian anatomy in patients
with cloacal abnormalities and the need for longitudinal assessment.
AB - INTRODUCTION: Most patients with a cloacal malformation have a Mullerian anomaly.
We sought to examine our patients with a cloacal malformation to determine the
proportion of them we felt we knew their Mullerian anatomy and which proportion
we felt would most benefit from longitudinal assessment to define their anatomy,
reproductive potential, and risk of outflow tract obstruction after puberty. We
also compared the preoperative assessment of reproductive anatomy (pelvic
ultrasound, MRI, cloacagram, and vaginoscopy) and intra-operative abdominal
findings (at the time of primary cloacal reconstruction or subsequent abdominal
procedures) to see how these correlated with and which preoperative assessment
tool was most predictive of intraoperative anatomy. We also sought to confirm
what we expected to be a lack of ovarian pathology. METHODS: A single site
retrospective chart review was performed on all patients with a cloacal anomaly
seen between May 2014 and September 2017. Preoperative assessment (pelvic
ultrasound, MRI, cloaca gram, and vaginoscopy) and operative reports (both
primary reconstruction and later abdominal procedures) were reviewed to ascertain
Mullerian and ovarian anatomy. RESULTS: 30 of 36 (83%) of patients had defined
Mullerian anatomy after preoperative assessment (pelvic ultrasound, MRI,
cloacagram, and vaginoscopy) with or without the addition intraoperative
assessment of Mullerian structures obtained during laparoscopy or laparotomy.
19/30 (63%) had duplication of their Mullerian structures. 25/36 (69%) had
intraoperative assessment of Mullerian anatomy during laparoscopy or laparotomy.
In this group, preoperative assessment with pelvic ultrasound correlated in 4/8
patients (50%), MRI correlated in 3/4 patients (75%), cloacagram in 10/15
patients (67%), and vaginoscopy in 23/25 patients (92%). 14/36 (39%) patients
were found to require longitudinal assessment to define anatomy, reproductive
potential or risk of outflow tract obstruction after puberty. Patients with
ovarian findings described at the time of laparoscopy or laparotomy had no
evidence of ovarian pathology. CONCLUSIONS: The majority of patients with cloaca
in our series (83%) had their Mullerian anatomy defined by either preoperative
assessment and/or findings at the time of laparoscopy or laparotomy. Duplication
of the vagina and uterus was the most commonly described Mullerian anatomy (63%)
in our series. Vaginoscopy appears to be superior to pelvic ultrasound, MRI, and
cloacagram in predicting Mullerian anatomy. Fourteen of our 36 (39%) patients
will require longitudinal assessment follow for reproductive potential and/or
risk of outflow tract obstruction after puberty as their Mullerian anatomy is not
known. There was no evidence of ovarian pathology in any cloaca patient. While we
felt as though we could define Mullerian anatomy in most of our patients, any
opportunity for intraoperative assessment of Mullerian anatomy should be utilized
and therefore teams who are involved in the management of these patients must
have a systematic and collaborative method established to ensure that Mullerian
structures are thoroughly evaluated intra-operatively and documented in a
standardized fashion. TYPE OF STUDY: Retrospective Chart review. LEVEL OF
EVIDENCE: III.
PMID- 29941358
TI - Predictors for surgical intervention and surgical outcomes in neonates with
cystic fibrosis.
AB - BACKGROUND/PURPOSE: To identify prenatal and perinatal predictors of surgery and
describe surgical findings/outcomes of neonates with Meconium Ileus (MI)
secondary to Cystic Fibrosis (CF). METHODS: Potential risk factors (prenatal
bowel echogenicity, CF genotype, birthweight, prematurity and sex) for MI and
surgery were examined in a retrospective cohort of neonates with CF presenting to
a tertiary center between 1997 and 2015. Following univariable analysis,
predictors of MI and surgery were determined using multivariable logistic
regression. For surgical patients, detailed operative findings and outcomes were
examined. RESULTS: MI was diagnosed in 26/120 (21.7%) neonates with CF and 19/26
(73.0%) required surgery. Prematurity was significantly associated with increased
risk of MI and operative intervention (p-value 0.022 and p-value 0.016
respectively); lower birthweight was associated with operative intervention (p
value 0.039); genotype and echogenic bowel were associated with neither. Surgical
data were available for 17/19 patients; median age at surgery was 2 days (IQR1
3), 4/17 had an atresia and 6/17 received an ostomy. Median NICU and hospital
stays were 34.5 and 70 days while median time on TPN and time to ostomy reversal
were 28.5 and 97 days, respectively. CONCLUSIONS: In patients with CF,
prematurity and lower birthweight were identified as risk factors for meconium
ileus and need for surgery. Specific genotypes and echogenic bowel were not
predictors of either. LEVEL OF EVIDENCE: Level III.
PMID- 29941359
TI - Phenylalanine ammonia lyase (PAL): From discovery to enzyme substitution therapy
for phenylketonuria.
AB - Phenylketonuria (PKU) is a genetic inborn error in metabolism that impacts many
people globally, with profound individual and societal consequences when left
untreated. The journey of phenylalanine ammonia lyase (PAL) from plant enzyme to
enzyme substitution therapy for PKU is a fascinating story that illustrates the
importance of collaboration between basic scientists and industry in the drug
development process. The story begins with the curiosity of plant physiologists
about the origin of lignin, a polymer involved in maintaining the rigidity of
plants. They learned that the critical element in this synthesis was an
intermediary enzyme that deaminates phenylalanine to cinnamic acid and ammonia
(later called phenylalanine ammonia lyase or PAL). Recognition of this ability to
metabolize phenylalanine led to subsequent consideration of PAL as a treatment
for PKU. This was initially attempted as enteral therapy with extracted enzyme,
but that showed only minimal efficacy. Crucially, further development of PAL as a
therapy for PKU required quantities of enzyme that could only be obtained after
successfully cloning the gene, expressing the enzyme in vitro and modifying the
protein via PEGylation to enable parenteral administration of this non-mammalian
enzyme. Ultimately, PEGylated PAL was developed as an enzyme substitution therapy
for PKU now approved under the name "Palynziq." The multidisciplinary academic
industrial partnership engaged throughout this process has been key to the
successful pursuit of this therapeutic possibility and serves as a model for the
development of future innovative therapies.
PMID- 29941360
TI - Digital PCR (dPCR) analysis reveals that the homozygous c.315-48T>C variant in
the FECH gene might cause erythropoietic protoporphyria (EPP).
AB - Alterations in the ferrochelatase gene (FECH) are the basis of the phenotypic
expressions in erythropoietic protoporphyria. The phenotype is due to the
presence of a mutation in the FECH gene associated in trans to the c.315-48 T > C
variant in the intron 3. The latter is able to increase the physiological quota
of alternative splicing events in the intron 3. Other two variants in the FECH
gene (c.1-252A > G and c.68-23C > T) have been found to be associated to the
intron 3 variant in some populations and together, they constitute a haplotype
(ACT/GTC), but eventually, their role in the alternative splicing event has never
been elucidated. The absolute number of the aberrantly spliced FECH mRNA
molecules and the absolute expression of the FECH gene were evaluated by digital
PCR technique in a comprehensive cohort. The number of splicing events that rose
in the presence of the c.315-48 T > C variant, both in the heterozygous and
homozygous condition was reported for the first time. Also, the percentage of the
inserted FECH mRNA increased, even doubled in the T/C cases, compared to T/T
cases. The constant presence of variants in the promoter and intron 2 did not
influence or modulate the aberrant splicing. The results of FECH gene expression
suggested that the homozygosity for the c.315-48 T > C variant could be
considered pathological. Thus, this study identified the homozygotes for the
c.315-48 T > C variant as pathological. By extension, when the samples were
categorised according to the haplotypes, the GTC haplotype in homozygosis was
pathological.
PMID- 29941361
TI - Total lower lip reconstruction with free forearm flap suspended on Adams wires.
PMID- 29941362
TI - Invasive aesthetic gynecology trends in Poland between 2010 and 2016: A
multicenter experience.
PMID- 29941363
TI - Latino/Hispanic Participation in Community Nutrition Research: An Interplay of
Decisional Balance, Cultural Competency, and Formative Work.
AB - BACKGROUND: Latinos/Hispanics are among the populations at high risk of nutrition
disparities. Adequate participation of this group in community nutrition research
is necessary to better understand such disparities and propose sensible
solutions. OBJECTIVE: To identify factors influencing participation and
strategies to effectively reach Latinos/Hispanics for community nutrition
research. DESIGN: In-depth interviews with experienced community nutrition
researchers across the United States, conducted from February to June 2013.
PARTICIPANTS/SETTING: Nine academics, including four registered dietitian
nutritionists with extensive experience in community nutrition research with
Latino/Hispanic groups, were interviewed in person (n=3) or via telephone/Skype
(n=6). MAIN OUTCOME MEASURES: Perceived participation barriers, facilitators, and
structural factors affecting Latino/Hispanic participation were explored.
Successful and unsuccessful recruitment strategies to reaching this group were
identified. ANALYSIS: A Grounded Theory approach was applied for inductive
identification of relevant concepts and deductive interpretation of patterns and
relationships among themes. RESULTS: Formative work, cultural competency, and
decisional balance emerged as the three interdependent factors influencing
participation of Latinos/Hispanics in community nutrition research. Several
approaches to influence participation were reported to be operationalized at the
interpersonal, community and settings, and systems levels of influence. Trust,
time, and tailoring were central concepts, postulated to moderate the
relationship between the main themes and influence the effectiveness of
recruitment tactics. CONCLUSIONS: Experienced community nutrition researchers
identified actions ascribed to formative work as the bedrock of successful reach
of Latinos/Hispanics. A robust formative work plan is necessary to achieving a
functional level of trust, time, and tailoring tactics, which appear to
critically influence participation.
PMID- 29941364
TI - A conserved Leishmania hypothetical protein evaluated for the serodiagnosis of
canine and human visceral and tegumentary leishmaniasis, as well as a serological
marker for the posttreatment patient follow-up.
AB - In the present study, a conserved Leishmania hypothetical protein, LiHyE, was
evaluated for the serodiagnosis of leishmaniasis. Results showed that it
presented high sensitivity, specificity, positive predictive value (PPV), and
negative predictive value (NPV) to serologically identify visceral leishmaniasis
(VL) dogs when 40 positive sera and 95 cross-reactive samples were used. rLiHyE
also showed the best results of sensitivity, specificity, PPV, and NPV to
identify tegumentary leishmaniasis (TL) and VL patients when 45 leishmaniasis
patients' sera and 90 cross-reactive samples were used. Results were better in
comparison to those obtained when rA2 or Leishmania antigenic extract was
employed as controls. The posttreatment follow-up showed that rLiHyE-specific
antibodies declined significantly after the end of treatments, and a predominance
of the IgG2 subclass was found in comparison to IgG1 levels in both TL and VL
patients. In conclusion, rLiHyE can be considered a candidate for the
serodiagnosis of canine and human leishmaniasis.
PMID- 29941365
TI - Comparison of clinical performance of commercial urine growth stabilization
products.
AB - INTRODUCTION: Urine specimens for quantitative culture for the diagnosis of
urinary tract infection may be unreliable due to bacterial overgrowth within 4 h
after collection, at room temperature. Because specimen transportation may take
longer than 4 h, urine preservatives may reduce overgrowth. Further evidence is
needed to support a recommendation for use of preservative and to compare
preservative products. METHODS: Consecutive midstream urine specimens submitted
for culture were quantitatively cultured on receipt and then inoculated into 3
storage conditions [BD Urine Vacutainer (BD), Copan UriSwab (US), and
refrigeration, with a room temperature control] for 72 h, with quantitative
culture performed every 24 h. Odds ratio for significant growth interpretation
was reported. RESULTS: Ninety-five of 501 (19.0%) urine specimens demonstrated
significant growth. Within 24 h of storage, unpreserved urine at room temperature
demonstrated a significantly increased odds ratio for significant growth as
compared to preserved urine, and urine in refrigeration demonstrated similar odds
ratio for significant growth as compared to preserved. There was no significant
difference between the performance of US and BD. Over 48 and 72 h of storage,
odds ratio for significant growth further increased. CONCLUSIONS: Preservation
performed similarly to refrigeration. Preserved urine demonstrated a doubling in
odds ratio for significant growth after 24 h. This increase may negatively impact
antibiotic treatment decisions.
PMID- 29941366
TI - A new dual-targeting real-time RT-PCR assay for hepatitis D virus RNA detection.
AB - In this study, a real-time reverse transcription-polymerase chain reaction (real
time RT-PCR) assay targeting 2 genetic segments was established to detect HDV
RNA. Utilizing the World Health Organization International Standard for Hepatitis
D Virus RNA, the lower limit of detection was 575 IU/mL, and the linearity of
quantification ranged from 575,000 IU/mL to 575 IU/mL. 384 HBsAg-positive samples
collected from China were tested by this method and HDV antibody detection.
Eleven samples were positive for anti-HDV IgG which may persist after HDV
resolution, 6 samples were HDV RNA positive, and 5 samples were positive for anti
HDV IgM. This assay showed more sensitivity than the detection of anti-HDV IgM.
These data demonstrate that the real-time RT-PCR assay for HDV RNA could be
implemented in the clinical detection of HDV infection in chronic HBV-infected
patients in China.
PMID- 29941367
TI - You can become a confident advocate for infection prevention.
PMID- 29941368
TI - Contaminated clothing of methicillin-resistant Staphylococcus aureus (MRSA)
carriers is a potential source of transmission.
AB - We examined the burden of methicillin-resistant Staphylococcus aureus (MRSA) on
the clothing of MRSA carriers in a hospital and long-term care facility and
assessed the potential for clothing to be a source of transmission. Of 50 MRSA
carriers studied, 37 (74%) had MRSA recovered from clothing. For a subset of
carriers with clothing contamination, transfer of MRSA from clothing to gloved
hands and to a wheelchair occurred in 8 of 13 (62%) and 5 of 10 (50%) carriers,
respectively. These findings suggest that measures to reduce clothing
contamination should be investigated as a potential means to reduce MRSA
transmission in healthcare settings.
PMID- 29941369
TI - Midterm Outcomes With the Self-Expanding ACURATE neo Aortic Bioprosthesis: The
"Bumblebee Paradox" in Transcatheter Aortic Valve Replacement.
PMID- 29941370
TI - Familial isolated hyperparathyroidism due to HRPT2 mutation.
PMID- 29941371
TI - Symptomatic Cholelithiasis of a Remnant Gallbladder after Open Cholecystectomy.
AB - BACKGROUND: Recurrent abdominal pain, particularly in the right upper quadrant
(RUQ) in a patient with a history of cholecystectomy, known as
postcholecystectomy syndrome, requires a broad differential diagnosis. Pathology
of a retained gallbladder remnant is an exceedingly rare etiology of this pain.
CASE REPORT: A 49-year-old woman who had previously undergone an open
cholecystectomy presented to the emergency department with several hours of
postprandial RUQ pain and emesis. Liver function tests and lipase were not
significantly elevated. RUQ ultrasonography revealed a cystic structure
containing a stone with mild prominence of the common bile duct at 7 mm, and
magnetic resonance cholangiopancreatography confirmed the presence of a remnant
gallbladder without common bile duct obstruction. Her pain subsided, she
tolerated a diet, and was discharged with a referral for an elective
cholecystectomy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Abdominal
pain is the most common chief complaint of patients presenting to the emergency
department in the United States, and emergency physicians routinely encounter
patients with postcholecystectomy syndrome. Emergency physicians should not
exclude the possibility of remnant gallbladder pathology, such as symptomatic
cholelithiasis or cholecystitis, in patients presenting with symptoms concerning
for biliary colic, even if the patient has undergone previous cholecystectomy.
PMID- 29941372
TI - Single-Use Laundry Detergent Pack Exposures in Children Under 6 Years: A
Prospective Study at U.S. Poison Control Centers.
AB - BACKGROUND: After the widespread introduction of single-use liquid laundry
detergent packs (LLDPs), a prospective observational study was initiated among 12
U.S. poison control centers (PCCs), serving 25% of the population. OBJECTIVES: To
evaluate qualitative and quantitative data, including demographics, route of
exposure, clinical effects, medical outcome, management site, level of care, and
circumstantial variables surrounding the LLDP exposure. METHODS: Analysis of LLDP
exposures involving children (age < 6 years) reported to PCCs participating in
the prospective study (March 2012-February 2016). PCCs captured a detailed
exposure history and followed each patient to symptom resolution. Each case
narrative was reviewed to isolate key patient, product, and situational variables
and to verify accuracy of coded data. Trend and comparative analyses were
performed on absolute case counts, relative proportions, and reporting rates
normalized using Nielsen consumption data. Separately, the impact of exposure
reduction interventions introduced by a single manufacturer were assessed by
comparing reporting rate during pre-/postintervention periods. RESULTS: There
were 11,175 childhood exposures reported, with 90.3% involving children aged <= 3
years. Ingestion (82.6%) and ocular (14.2%) were the major routes of exposure.
The size of the market for LLDPs more than doubled from ~2.0 to ~4.6 million
LLDPs purchased. Total exposure reports increased from Year 1 (n = 2297) to Year
4 (n = 3206), however, normalized reporting rates dropped by 37% (4.4 to 2.8
exp/million LLDPs purchased). Significant declines (p < 0.0001) were also
observed for ingestions and ocular exposures with major/moderate outcome.
CONCLUSIONS: There was a significant reduction in exposures that resulted in
major/moderate outcomes, and the majority of patients did not require
intervention in an emergency department setting.
PMID- 29941373
TI - Editorial.
PMID- 29941374
TI - Cardiac Toxicity from Intentional Ingestion of Pong-Pong Seeds (Cerbera Odollam).
AB - BACKGROUND: A variety of plants contain cardiac glycosides. This has resulted in
many of them being used to commit suicide. In southeast Asia, Cerebera odollam
(pong-pong or suicide tree) is frequently used for suicidal ingestion. Seeds, or
kernels, of this plant can cause hyperkalemia, heart block, and death due to the
effects of its cardiac glycosides. CASE REPORT: We describe six cases of pong
pong seed ingestion reported to US poison centers. The most common symptoms were
vomiting and bradycardia. Three patients survived and three died. All patients
who died had heart block, serum digoxin levels > 1.0 ng/mL, and were treated with
anti-digoxin immune FAB. Anti-digoxin immune FAB may be ineffective in a large
pong-pong seed ingestion. Patients ingesting pong-pong seeds who develop a
potassium level > 8.0 meq/L or have a digoxin level > 1.0 ng/mL may be at a
higher risk for death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The
apparent ease of acquiring C. odollam seeds on the Internet makes knowledge of it
important, as it can be used as a means to commit suicide. The apparent failure
of digoxin immune FAB to treat toxicity from pong-pong is important, as other
lifesaving techniques, such as extracorporeal membrane oxygenation, might be
needed in severely toxic patients.
PMID- 29941375
TI - Intracerebral Abscess: An Uncommon Complication of Cystic Fibrosis.
PMID- 29941376
TI - An Eye with a Heartbeat: Carotid Cavernous Fistula-a Case Report.
AB - BACKGROUND: A carotid cavernous fistula is a rare type of arteriovenous (AV)
fistula due to an abnormal communication between the cavernous sinus and the
carotid arterial system. Normal venous return to the cavernous sinus is impeded
as high-pressure arterial blood enters the cavernous sinus. The classical triad
of symptoms is characterized by pulsating exophthalmos, ocular bruit, and
conjunctival chemosis. However, it is important to note that some patients do not
exhibit this triad of symptoms. CASE REPORT: A 49-year-old man presented to the
Emergency Department (ED) with a chief complaint of "there is a heartbeat in my
eye." Pertinent history included an episode of trauma 2 months prior to his onset
of unilateral vision loss. Computed tomography scan of the head obtained in the
ED upon his initial injury was unrevealing. Despite no identifiable pathology,
his pain had gradually worsened since ED discharge. On this occasion, an ocular
bruit was appreciated over the affected eye, prompting further diagnostic
testing. The patient was admitted for urgent cerebral angiography and definitive
endovascular neurosurgical intervention to preserve his eyesight. We discuss the
clinical presentation, pathophysiology, and diagnostic modalities important to
the management of this rare and potentially devastating cause of vision loss. WHY
SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A carotid cavernous fistula is a
rare and easily misdiagnosed cause of unilateral ocular pain in the ED. Further,
it emphasizes the importance of a detailed clinical history and physical
examination to make this diagnosis and save eyesight.
PMID- 29941377
TI - A meritorious move against homeopathy.
PMID- 29941378
TI - Association between presenting complaints of acutely admitted medical patients
and mortality: A cohort study.
PMID- 29941379
TI - Estimates of adults with indications for HIV pre-exposure prophylaxis by
jurisdiction, transmission risk group, and race/ethnicity, United States, 2015.
AB - PURPOSE: Effectively measuring progress in delivering HIV pre-exposure
prophylaxis (PrEP) requires subnational estimates of the number of adults with
indications for its use that account for differences in HIV infection rates by
transmission risk (risk) group and race/ethnicity. METHODS: We applied a
multiplier method with 2015 Centers for Disease Control and Prevention
surveillance data on proportions of HIV diagnoses by race/ethnicity and risk
group and population-based estimates of risk group sizes to derive estimated
numbers of adults with indications by risk group (men who have sex with men
[MSM], heterosexually active adults [HET], and persons who inject drugs [PWID])
by race/ethnicity in each jurisdiction. RESULTS: An estimated 1.1 million adults
had indications for PrEP use in 2015: 813,970 MSM, 258,080 HET, and 72,510
persons who inject drugs, and 500,340 blacks, 282,260 Latinos, and 303,230
whites. Among HET, 176,670 females and 81,410 males had indications. The
proportions of adults with indications in each risk and race/ethnicity group
varied by jurisdiction. CONCLUSIONS: Blacks comprised the highest number of
adults with indications showing that increasing PrEP use in this population must
be the highest priority. MSM remain a priority because of the high number with
indications. These estimates can be used as denominators to assess PrEP coverage
and impact on HIV incidence at subnational levels.
PMID- 29941380
TI - Effect of Ibuprofen on BrainAGE: A Randomized, Placebo-Controlled, Dose-Response
Exploratory Study.
AB - BACKGROUND: The age of a person's brain can be estimated from structural brain
images using an aggregate measure of variation in morphology across the whole
brain. The brain age gap estimation (BrainAGE) score is computed as the
difference between kernel-estimated brain age and chronological age. In this
exploratory study, we investigated the application of the BrainAGE measure to
identify potential novel effects of pharmacological agents on brain morphology.
METHODS: Twenty healthy participants (23-47 years of age) completed three
structural magnetic resonance imaging scans 45 minutes after administration of
placebo or 200 or 600 mg of ibuprofen in a double-blind, crossover study. An
externally derived BrainAGE model from a sample of 480 healthy participants was
used to examine the acute effect of ibuprofen on temporary neuroanatomical
changes in healthy individuals. RESULTS: The BrainAGE model produced age
prediction for each participant with a mean absolute error of 6.7 years between
the estimated and chronological age. The intraclass correlation coefficient for
BrainAGE was 0.96. Relative to placebo, 200 and 600 mg of ibuprofen significantly
decreased BrainAGE by 1.18 and 1.15 years, respectively (p < .05). The trained
BrainAGE model identified the medial prefrontal cortex to be the strongest age
predictor. CONCLUSIONS: BrainAGE is a potentially useful construct to examine
neurological effects of therapeutic drugs. Ibuprofen temporarily reduces BrainAGE
by approximately 1 year, which is likely due to its acute anti-inflammatory
effects.
PMID- 29941381
TI - No Difference in Morbidity and Mortality After Total Joint Arthroplasty in Liver
Transplant Recipients: A Propensity Score-Matched Analysis of a Nationwide,
Population-Based Study Using Universal Healthcare Data.
AB - BACKGROUND: Controversy remains regarding the outcomes after total joint
arthroplasty (TJA) among patients with or without liver transplantation (LT).
This study aimed at investigating the prevalence of TJA in patients after LT and
comparing the morbidity and mortality with the non-LT group. METHODS: We
conducted a nationwide, population-based study, with data extracted from a
universal health insurance database, based on the International Classification of
Disease, Ninth Revision, Clinical Modification. Patients who underwent TJAs
between January 2001 and December 2014 were included. Patients who had bilateral
TJAs or a TJA before LT were excluded. A total of 43 patients with LT and 350,337
patients without LT were included. The analysis was implemented using data from
all patients and those matched by 1-to-10 propensity score matching.
Multivariable logistic regression was used to control confounding variables.
RESULTS: The prevalence of patients undergoing TJA after LT was 1.3% (43/3276).
After propensity score matching, patients with LT were not associated with 30-day
complications (adjusted odds ratio [aOR], 0.98; 95% confidence interval [CI],
0.93-1.03; P = .35), 30-day readmission rates (aOR, 0.93; 95% CI, 0.92-1.08; P =
.87), 90-day complication rates (aOR, 0.95; 95% CI, 0.88-1.02; P = .16), 1-year
infection rates (aOR, 1.04; 95% CI, 0.96-1.12; P = .35), reoperation rates (aOR,
1.06; 95% CI, 0.92-1.23; P = .41), or mortality (aOR, 0.91; 95% CI, 0.80-1.04; P
= .18). CONCLUSION: The morbidity and mortality seem to be comparable whether TJA
is performed in patients with or without LT. Methods for risk assessment would be
feasible in liver transplant recipients.
PMID- 29941382
TI - Gait Abnormality Predicts Falls in Women After Total Hip Arthroplasty.
AB - BACKGROUND: Patients who undergo total hip arthroplasty (THA) have an increased
risk of falls during the first year postoperatively. However, risk factors for
falls after THA remain unclear. We investigated the relationship between gait
abnormality and falls during the first year after THA. METHODS: We conducted a
prospective cohort study of 286 patients with severe hip osteoarthritis who
underwent THA and examined fall history during the first year postoperatively.
Baseline characteristics including age, body mass index, number of prescribed
medications, comorbidities, and history of falling in the past year were
evaluated as covariates and determined using a self-administered questionnaire
and interview preoperatively. We assessed functional outcomes, including passive
range of motion of the hip joint (flexion, extension, abduction, and adduction),
muscle strength (hip abduction and knee extension), gait velocity, and gait
abnormality, at 3 weeks postoperatively. Cox proportional hazard regression
models were used to analyze the relationship between the presence of gait
abnormality and falls. RESULTS: One hundred sixty-two women were included. The
incidence of at least 1 fall during the first year after THA was 31.5%. Cox
proportional hazard regression models showed that the presence of gait
abnormality (hazard ratio, 2.91; 95% confidence interval, 1.55-5.48; P < .001)
was significantly associated with falls during the first year postoperatively.
CONCLUSION: The presence of gait abnormality is a useful screening tool to
predict future falls in women after THA. Clinicians should assess gait
abnormality to identify patients who may require fall prevention measures and
continuous rehabilitation to improve gait abnormality.
PMID- 29941383
TI - Comparative virulence characterization of the Shiga toxin phage-cured Escherichia
coli O104:H4 and enteroaggregative Escherichia coli.
AB - Escherichia coli O104:H4 (E. coli O104:H4), which caused in 2011 a massive
foodborne outbreak in Germany, is characterized by an unusual combination of
virulence traits. E. coli O104:H4 contains a prophage-encoded Shiga toxin (Stx)
gene, which is the cardinal virulence factor of enterohemorrhagic E. coli (EHEC).
However, the outbreak strain shares highest DNA sequence similarity with
enteroaggregative E. coli (EAEC) and displays the EAEC-characteristic tight
adherence to epithelial cells. The virulence potential of the underlying EAEC
background has not been investigated and it is therefore not clear whether E.
coli O104:H4 displays distinct virulence characteristics in comparison to
prototypical EAEC. In this study, we performed a detailed comparative phenotypic
characterization of the Stx phage-cured E. coli O104:H4 strain C227-11phicu, the
closely related EAEC strain 55989 and two other well-characterized EAEC strains
042 and 17-2 with focus on virulence traits. C227-11phicu displayed superior
aggregative adherence phenotype to cultured HCT-8 epithelial cells, adhering with
3-6 times more bacteria per epithelial cells than the tested EAEC strains.
Otherwise, C227-11phicu showed similar virulence characteristics to its closest
relative 55989, i.e. strong acid resistance, good biofilm formation and cytotoxic
culture supernatants. Furthermore, C227-11phicu was characterized by
significantly weaker motility and pro-inflammatory properties than 55989 and 042,
nevertheless stronger than 17-2. Taken together, C227-11phicu displayed mostly
robust, but not outstanding virulence characteristics in comparison to the tested
EAEC. Therefore, it appears likely that the combination of Stx production and
EAEC characteristics in general, rather than an exceptionally potent EAEC
background resulted in the unusual virulence of the E. coli O104:H4. Thus, the
emergence of such hypervirulent strains in the future might be more likely than
previously anticipated.
PMID- 29941384
TI - Analysis of Staphylococcus aureus proteins secreted inside infected human
epithelial cells.
AB - Staphylococcus aureus, an opportunistic pathogen is able to invade into and
persist inside non-professional phagocytic cells. To do so, this bacterium
possesses a wide range of secreted virulence factors which enable attachment to
the host as well as intracellular survival. Hence, a monitoring of virulence
factors specifically produced upon internalization might reveal targets for
prevention or therapy of S. aureus infections. However, previous proteome
approaches enriching S. aureus from lysed host cells after infection did not
cover secreted virulence factors. Therefore, we used density gradient
centrifugation and mass spectrometry to identify S. aureus HG001 proteins which
were secreted into compartments of infected human bronchial epithelial S9 cells.
Because shotgun mass spectrometry revealed only few bacterial proteins amongst
1905 host proteins, we used highly sensitive and selective single reaction
monitoring mass spectrometry as an alternative approach and quantified 37
bacterial proteins within the S. aureus containing host cell compartment 2.5 h
and 6.5 h post infection. Among them were secreted bacterial virulence factors
like lipases, pore forming toxins, and secreted adhesins which are usually hard
to detect from infected sample material by proteomics approaches due to their low
abundance. S. aureus adapted its proteome to improve its response to oxidative
and cell wall stress occurring inside the host, but also, increased the amounts
of some adhesins and pore-forming toxins, required for attachment and host cell
lysis.
PMID- 29941385
TI - Transabdominal Direct Sac Puncture Embolization of Type II Endoleaks after
Endovascular Abdominal Aortic Aneurysm Repair.
AB - PURPOSE: To determine the efficacy and safety of transabdominal direct sac
puncture embolization of type II endoleaks after endovascular abdominal aortic
aneurysm repair (EVAR). MATERIALS AND METHODS: This retrospective review included
30 patients (4 women, 26 men; mean age = 79.1 years) who underwent 33
transabdominal direct sac puncture embolization procedures for type II endoleaks
after EVAR. Embolization agents included cyanoacrylate glue only (45.5%),
glue/coils (36.4%), and Onyx with or without glue/coils (18.1%). Technical
success was defined as complete endoleak embolization on intraprocedural
fluoroscopy. The primary outcome was freedom of aneurysm growth, which was
defined as <= 5% aneurysm sac volume change on follow-up computed tomography (CT)
imaging or <= 5 mm aneurysm sac diameter change on ultrasound without definite
endoflow. Aneurysm sac volumes before and after embolization were manually
segmented from CT images. The procedural complication rate was calculated.
RESULTS: Technical success was achieved in 97% of patients (29/30). Follow-up
imaging was available in 27 patients (25 CT; 2 ultrasound), and mean imaging
follow-up duration was 15.5 months. Freedom of aneurysm growth was achieved in
85.2% of patients (23/27) after 1 or more embolization procedures. Median
fluoroscopic and procedure times were 11.3 minutes and 90 minutes, respectively.
The complication rate was 9.1% (3/33) and included 1 case of nontarget
embolization with transient neuropraxia and 2 self-limiting rectus sheath
hematomas relating to the percutaneous puncture site. No aneurysm-related
mortality occurred during the follow-up period. CONCLUSIONS: Percutaneous
transabdominal embolization is a safe and efficacious treatment for type II
endoleak, with a short procedure time.
PMID- 29941386
TI - Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis
based on a case reports systematic survey.
AB - INTRODUCTION: Solitary plasmacytoma is a rare malignant tumor of plasma cells
with no evidence of systemic proliferation. There are two known subtypes:
extramedullary solitary plasmacytoma and solitary bone plasmacytoma. The etiology
is still unknown. Both lesions present a risk of progression to multiple myeloma.
A number of approaches have been used for treatment of solitary plasmacytoma.
OBJECTIVE: To carry out a systematic review of the case reports described in the
literature, focusing on therapeutic and prognostic aspects. METHODS: A search of
clinical case reports was performed in the PubMed database using Mesh Terms
related to "plasmacytoma" under the following criteria: type of study (case
report), articles in English language, conducted in humans, with no publication
date limits. RESULTS: Of the 216 articles found, only 21 articles met the pre
established inclusion criteria. CONCLUSION: The occurrence of solitary bone
plasmacytoma in the bones of the face is a rare condition prevalent between the
4th and 6th decades of life, located in the posterior region of the mandible in
most cases. Histopathological examination and systemic investigation are
mandatory for confirmation of diagnosis.
PMID- 29941387
TI - Social capital and depression among migrant hypertensive patients in primary
care.
AB - This study was to investigate prevalence of depression among migrant hypertensive
patients in primary care and to examine hypertensive patients' social capital and
its relationship with the prevalence of depression. An on-site-based cross
sectional study was performed in Shenzhen, China. A total of 830 migrant
hypertensive patients completed the survey by using systematic sampling design. A
questionnaire including information of depressive symptoms and social capital was
administered by face-to-face interview surveys. We found that the prevalence of
depression was 11.0% among migrant hypertensive patients in primary care. Social
ties (odds ratio = 1.197, 95% confidence interval: 1.034, 1.387) and trust (odds
ratio = 2.061, 95% confidence interval: 1.342, 3.165) were statistically
significant associated with the prevalence of depression. Our study shows that
the prevalence of depression is high among migrant hypertensive patients in
primary care. It also suggests an inverse association between social capital and
depression among migrant hypertensive patients. Although causal pathways between
social capital and depression cannot be established by the present study, it is
plausible to design and implement social interventions to improve mental health
of migrant hypertensive patients in primary care.
PMID- 29941388
TI - Over 30-yr Experience on the Management of Graft Stones After Renal
Transplantation.
AB - BACKGROUND: Urolithiasis has been reported in up to 1.8% of patients after renal
transplantation. Limited data are available regarding the treatment of such
patients owing to this low prevalence. OBJECTIVE: To analyse a consecutive series
of 2115 renal transplantations to elucidate the prevalence of renal graft stones
(RGS) and their treatment. DESIGN, SETTING, AND PARTICIPANTS: A retrospective
review was performed of a consecutive series of renal transplants from 1983 to
2017. Demographic and specific data regarding symptomatology, diagnosis, and
treatment of RGS were recorded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
Quantitative and qualitative variables were described. Differences in clinical
variables were evaluated using unpaired t test. Statistical significance was set
at p<0.05. RESULTS AND LIMITATIONS: In total, 51 patients (2.4%) were diagnosed
with de novo RGS. Mean stone size was 9+/-6.5mm, 31.4% being multiple stones. The
distal ureter was the most common location (49%). Treatment modalities were
extracorporeal shock wave lithotripsy (ESWL; 43.1%), active surveillance (25.4%),
retrograde ureteroscopy (URS; 17.6%), antegrade URS (3.9%), percutaneous
nephrolithotomy (3.9%), open approach (3.9%), and urine alkalisation (2%). Seven
(13.7%) patients developed complications: two haematuria, three urinary tract
infection, one steinstrasse, and one sepsis. Median follow-up was 72 mo. Overall
stone-free rate was 52.9%. No significant differences were observed between mean
glomerular filtration rate before and after treatment (p=0.642). There were no
cases of graft loss. Limitations include the retrospective nature of the study
and limited number of patients. CONCLUSIONS: RGS is an uncommon complication.
ESWL, endoscopic surgery, and surveillance have been used to treat or follow up
such patients. In well-selected patients, endourological surgery appears to
achieve better outcomes. RGS does not have a long-term impact on graft function
or graft survival. PATIENT SUMMARY: It is uncommon to develop stones in the
transplant kidney. If such stones are properly diagnosed, several minimally
invasive treatment options can yield good results while maintaining good renal
function.
PMID- 29941389
TI - Antimicrobial Lubricant Did Not Reduce Infection Rate in Transrectal Biopsy
Patients in a Large Randomized Trial Due to Low Complication Rates.
AB - BACKGROUND: Transrectal prostate biopsy (pbx) is the most frequent outpatient
procedure in the urological field. Septic complications are a major health issue.
OBJECTIVE: To evaluate complication rates with or without an antimicrobial
lubricant. DESIGN, SETTING, AND PARTICIPANTS: A total of 1000 patients received
pbx between 2013 and 2015. Information about complications was collected by a 3
wk questionnaire. Return rate was 73.2% (n=732). INTERVENTION: Randomization for
pbx with the instillation of an antimicrobial lubricant (intervention group,
n=385) or the standard lubricant (control group, n=347) was performed. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable analyses assessed the
association between infectious complications at biopsy and use of an
antimicrobial lubricant, International Prostate Symptom Score (IPSS), history of
urogenitourinary infections, and several other confounders. RESULTS AND
LIMITATIONS: The use of an antimicrobial lubricant did not reduce infection rate.
Overall complication rate was very low. Of all patients, 69.3% described the
procedure as pain free. Fever >=38.5 degrees C was reported in overall 1.9% of
patients. Urinary retention with catheterization occurred in 3.1%. Most common
complications were hematospermia (47.4%), macrohematuria (23.8%), and rectal
bleeding (7.4%). Readmission rate was 1% (n=7). In multivariable analyses, IPSS
and previous infectious complications were associated with a higher risk of
infectious complications. Our results stem from a large German single center and
therefore are limited to this patient group. CONCLUSIONS: No significant
reduction was shown in infectious complications in the intervention group with
the antimicrobial agent. Low incidence of those complications may be the
underlying cause. Severe morbidity at pbx is uncommon. Specifically, the rate of
infection was very low. PATIENT SUMMARY: Severe complications at prostate biopsy
are rare. Among participants, 69.3% had no pain. Fever was rare (1.9% of
patients). Voiding issues with catheterization occurred in 3.1%. Most common
complications were blood in the semen (47.4%), urine (23.8%), or stool (7.4%).
Men with voiding issues or previous infectious complications had a higher risk of
infectious complications.
PMID- 29941390
TI - BRCAness Combined With a Family History of Cancer Is Associated With a Poor
Prognosis for Breast Cancer Patients With a High Risk of BRCA Mutations.
AB - BACKGROUND: The inexpensive prediction of the characteristics of BRCA-mutated
breast cancer as "BRCAness" using the somatic cells of patients with breast
cancer could be useful for developing a therapeutic strategy. Our objective was
to correlate BRCAness with the clinicopathologic features, including a family
history (FH) of cancer, in breast cancer patients with a high risk of BRCA
mutations. PATIENTS AND METHODS: The present study included 124 patients,
including 55 with early-onset and 77 with triple-negative breast cancer, who had
undergone resection at Kyushu University Hospital from 2005 to 2014. Early-onset
breast cancer is defined as an onset in patients aged <= 40 years. BRCAness was
performed using multiple ligation-dependent probe amplification. The patients' FH
of cancer was surveyed from first- to third-degree relatives. RESULTS: Of the 124
patients, the multiple ligation-dependent probe amplification assay results
indicated that 59 tumors (47.6%) had BRCAness and 27 patients (21.8%) had a
positive FH for cancer. The patients with BRCAness experienced significantly
shorter recurrence-free survival (RFS) and overall survival (OS) compared with
those without. Patients with FH had shorter RFS and OS compared to those without
BRCAness. The patients were divided into those with and without BRCAness and
those with and without a positive FH. The BRCAness with FH subgroup experienced
significantly shorter RFS and OS. Multivariate analysis revealed that BRCAness
and a positive FH were independent negative prognostic factors. CONCLUSION: Our
findings suggest that BRCAness tumors with a positive FH of cancer were
associated with a poor prognosis in the BRCA-mutation high-risk group. We propose
that BRCAness and a positive FH will serve to predict patients' prognosis.
PMID- 29941391
TI - Tumor Site and Breast Cancer Prognosis.
AB - INTRODUCTION: Various factors affect breast cancer prognosis; however, little
information is available regarding the role of primary tumor site. The purpose of
this study was to compare the survival and clinicopathologic characteristics of
patients with breast cancer by primary tumor location. MATERIALS AND METHODS: We
analyzed a prospectively collected single-institution breast cancer registry.
Univariate and multivariable analyses were used to evaluate the association of
tumor site with positive lymph node status, presence of metastasis, time to
recurrence or death, and events of recurrence or death. Patients with tumors
originating from the upper-outer quadrant were the reference group. RESULTS: From
2003 to 2015, 5295 patients with breast cancer were identified. Tumors originated
from the upper-outer quadrant (36.2%), upper-inner quadrant (13.1%), lower-outer
quadrant (9.8%), lower-inner quadrant (7.6%), nipple (1.2%), axillary tail
(0.3%), or overlapping (24.7%). Tumors originated from overlapping lesions (odds
ratio [OR], 1.58; 95% confidence interval [CI], 1.36-1.83) had higher odds of
positive axillary lymph nodes, whereas tumors from the upper-inner (OR, 0.68; 95%
CI, 0.56-0.84) and lower-inner quadrant (OR, 0.72; 95% CI, 0.56-0.93) had lower
odds. Tumors from the lower-outer quadrant were associated with lower risk of
death (hazard ratio, 0.64; 95% CI, 0.46-0.88), whereas tumors from overlapping
lesions had higher risk (hazard ratio, 1.28; 95% CI, 1.05-1.55). CONCLUSION: The
site of primary tumor may be an important characteristic affecting the prognosis
of patients with breast cancer.
PMID- 29941392
TI - Influence of Contralateral Carotid Occlusion on Outcomes After Carotid
Endarterectomy: A Meta-Analysis.
AB - BACKGROUND: There is a controversy about whether the contralateral carotid
occlusion (CO) in patients undergoing carotid endarterectomy (CEA) is associated
with worse early and long-term outcomes. The aim of this systematic review and
meta-analysis was to investigate the impact of CO on outcomes after CEA. METHODS:
PubMed, Embase, and MEDLINE databases were searched until January 2018 for
studies comparing early and long-term outcomes of CEA in patients with CO and
with patent contralateral carotid (CP). Two independent reviewers identified
studies meeting our inclusion/exclusion criteria, extracted relevant data and
assessed quality. Fixed- or random-effects models were used to calculate the
overall effect estimates. RESULTS: Our literature search identified 35 articles
eligible for inclusion in the review and analysis. Patients with CO had higher
rate of preoperative symptoms (Stroke + transient ischemic attack [TIA]) (odds
ratio [OR] = 1.20, 95% confidence interval [CI]: 1.11-1.31) and had increased
risk of perioperative neurological complications (Stroke + TIA) (OR = 1.63, 95%
CI: 1.36-1.94) compared with those with CP. No significant difference in the
perioperative mortality rate (OR = 1.40, 95% CI: .99-1.98) and the stroke-free
survival rate at 5 years (OR = 1.06, 95% CI: .79-1.40) between 2 groups was
identified. CONCLUSIONS: The presence of CO results in higher rate of
preoperative symptoms and increases perioperative risk of neurological
complications in CEA, but do not have a significant impact on the perioperative
mortality rate and the stroke-free survival rate at 5 years. Careful
consideration should be given in perioperative care in these patients.
PMID- 29941393
TI - Association of Urinary Incontinence with Cognition, Transfers and Discharge
Destination in Acute Stroke Inpatient Rehabilitation.
AB - BACKGROUND: Acute-stroke prognostic indicators remain controversial including
relationship of urinary incontinence with outcomes in cognition, transfers, and
discharge destination. OBJECTIVE: To examine if urinary incontinence is
associated with inpatient-rehabilitation (IR) outcomes in cognition, transfers,
and discharge destinations. DESIGN: Retrospective observational study of 303 of
579(52%) acute-stroke patients admitted to IR 2012-2015 with complete urinary
incontinence (total assistance for bladder management). Discharge Functional
Independence Measure (FIM) scores were correlated for continence, cognition,
transfers-(bed/chair/wheelchair), and discharge destination. RESULTS: Patients
were admitted to IR on average 7.4 days after acute stroke. Average length-of
stay in IR was 14 days. At discharge 118 of 303(39%) remained urinary incontinent
(total assistance). Continence/bladder-management FIM scores at discharge were
associated with cognition FIM scores at discharge (chi square =105.8; P < .0001),
and associated with transfer FIM scores at discharge (chi square = 153.1; P <
.0001). Patients total to moderate assistance for continence at discharge
included greater percentage that were dependent to moderate assistance for
cognition and transfers than those minimal assistance to independent for
continence. Continence/bladder-management FIM scores at discharge were associated
with discharge disposition destinations (chi square = 29.98; P < .002). Patients
total to moderate assistance for continence at discharge included greater
percentage of acute care transfers, and skilled-nursing-facility dispositions,
than patients that recovered to minimal assist to independent for continence.
Urinary-incontinence recovery to minimal assistance to independent was associated
with a home/community disposition rate of 82%. CONCLUSIONS: 52% stroke patients
were total assistance with bladder management for urinary incontinence on IR
admission. Partial to complete continence recovery occurred in 61%.
Continence/bladder-management FIM scores at discharge were associated with
cognition and transfer FIM scores, and discharge destinations.
PMID- 29941394
TI - The JAGUAR Score Predicts 1-Month Disability/Death in Ischemic Stroke Patient
Ineligible for Recanalization Therapy.
AB - BACKGROUND AND PURPOSE: Most available scoring system to predict outcome after
acute ischemic stroke (AIS) were established in Western countries. We aimed to
develop a simple prediction score of 1-month severe disability/death after onset
in AIS patients ineligible for recanalization therapy based on readily and widely
obtainable on-admission clinical, laboratory and radiological examinations in
Asian developing countries. METHODS: Using the Shiga Stroke Registry, a large
population-based registry in Japan, multivariable logistic regression analysis
was conducted in 1617 AIS patients ineligible for recanalization therapy to yield
beta-coefficients of significant predictors of 1-month modified Rankin Scale
score of 5-6, which were then multiplied by a specific constant and rounded to
nearest integer to develop 0-10 points system. Model discrimination and
calibration were evaluated in the original and bootstrapped population. RESULTS:
Japan Coma Scale score (J), age (A), random glucose (G), untimely onset-to
arrival time (U), atrial fibrillation (A), and preadmission dependency status
according to the modified Rankin Scale score (R), were recognized as independent
predictors of outcome. Each of their beta-coefficients was multiplied by 1.3
creating the JAGUAR score. Its area under the curve (95% confidence interval) was
.901 (.880- .922) and .901 (.900- .901) in the original and bootstrapped
population, respectively. It was found to have good calibration in both study
population (P = .27). CONCLUSIONS: The JAGUAR score can be an important
prediction tool of severe disability/death in AIS patients ineligible for
recanalization therapy that can be applied on admission with no complicated
calculation and multimodal neuroimaging necessary, thus suitable for Asian
developing countries.
PMID- 29941395
TI - Association between high-density lipoprotein subfractions and low-grade
inflammation, insulin resistance, and metabolic syndrome components: The ELSA
Brasil study.
AB - BACKGROUND: High-density lipoprotein cholesterol (HDL-C) can be divided into
subfractions, which may have variable effects in atherogenesis. The results about
the association between HDL-C subfractions and risk factors for cardiovascular
disease are mixed. OBJECTIVE: The objective of this study was to analyze the
association between HDL-C subfractions and each metabolic syndrome component,
homeostasis model assessment-estimated insulin resistance (HOMA-IR) and C
reactive protein (CRP). METHODS: Four thousand five hundred thirty-two
individuals between 35 and 74 years old without previous manifest cardiovascular
disease not using fibrates were enrolled. HDL-C subfractions were separated by
vertical ultracentrifugation (vertical auto profile-in mg/dL) into HDL2-C and
HDL3-C. HDL2-C/HDL3-C ratio, HOMA-IR, and high-sensitivity CRP were also included
in the analysis. RESULTS: Mean age of participants was 51 +/- 9 years, and 54.8%
were women. In univariate analysis, HDL-C, HDL2-C, and HDL3-C were all inversely
associated with each of the metabolic syndrome defining factors, HOMA-IR values,
and serum CRP. We also observed a negative association between HDL2-C/HDL3-C
ratio with the variables aforementioned even after adjusting for smoking, alcohol
use, physical activity, and HDL-C levels (P < .01). CONCLUSION: HDL-C and its
subfractions (HDL2-C and HDL3-C) are inversely associated with the defining
features of metabolic syndrome, insulin resistance, and systemic inflammation. In
addition, the HDL2-C/HDL3-C ratio measured by vertical auto profile is
significantly associated with the former factors even after comprehensive
adjustment for HDL-C and other confounding variables.
PMID- 29941396
TI - The ODYSSEY Outcomes trial: Clinical implications and exploration of the limits
of what can be achieved through lipid lowering.
PMID- 29941397
TI - The Long-To-Short-Axis Ratio and Multifocality are Associated With TP53 Mutation
Status in Surgically Resected Hepatocellular Carcinomas.
AB - RATIONALE AND OBJECTIVES: In hepatocellular carcinoma (HCC), the tumor protein 53
(TP53) gene is frequently mutated and the mutations have been associated with
poor prognosis. We aim to retrospectively identify the relationship between TP53
mutation status, tumor size (long-axis diameter, short-axis diameter, and long-to
short-axis ratio [L/S ratio]), margin and multifocality in surgically resected
HCC. MATERIALS AND METHODS: The image features and TP53 mutation data from 78
patients generated with National Cancer Institute's multi-institutional The
Cancer Genome Atlas (TCGA)/The Cancer Imaging Archive databases were assessed.
Binary logistic regression analyses were performed to identify independent
factors of harboring TP53 mutation status. The final model was selected by using
the backward elimination method. RESULTS: TP53 mutations were found in 19 (31.5%)
of 78 patients. TP53 mutation rates were significantly higher (a) in L/S ratio <=
1.2 14 of 41 [34.1%]) lesions than in L/S ratio >1.2 lesions (five of 37 [13.5%])
(p = 0.034) and (b) in nonmultifocality (17 of 54[31.5%]) than in multifocality
lesions (two of 24 [8.3%]) (p = 0.028). On univariate logistic regression
analysis, L/S ratio (<=1.20vs >1.20. odds ratio [OR]: 3.319; p = 0.040; 95%
confidence interval [CI]: 1.059-10.401 Area Under Curve (AUC) = 0.634) and
multifocality (no vs yes OR: 5.054; p = 0.041; 95% CI: 1.065-23.986 AUC = 0.640)
were associated with TP53 mutations. On multivariate logistic regression
analysis, L/S ratio (<=1.20vs >1.20 OR: 3.430; p = 0.040; 95% CI: 1.058-11.118)
and multifocality (no vs yes OR: 5.232; p = 0.041; 95% CI: 1.072-25.526) were
associated with TP53 mutations. The area under the receiver operating
characteristic curve for predicting TP53 mutation status was 0.714 (95% CI: 0.590
0.837). CONCLUSION: Our study focusing on identifying imaging aspects related to
TP53 positive HCC. L/S ratio of HCC in combination with multifocality might be
used to prognosticate TP53 mutation status. And the discriminatory power for this
prediction model was good.
PMID- 29941398
TI - Association Between BRAFV600E Mutation and the American College of Radiology
Thyroid Imaging, Reporting and Data System in Solitary Papillary Thyroid
Carcinoma.
AB - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the
associations between BRAFV600E mutation, the American College of Radiology (ACR)
thyroid imaging, reporting and data system (TI-RADS) on ultrasound and
clinicopathological characteristics in patients with a solitary papillary thyroid
carcinoma (PTC). MATERIALS AND METHODS: This retrospective study included 397
patients with a solitary PTC, proved pathologically. BRAFV600E mutation status
was detected in postoperative samples by real-time fluorescent polymerase chain
reaction. Associations of BRAFV600E mutation with the ACR TI-RADS and
clinicopathological characteristics were analyzed. RESULTS: In this study, the
incidence of BRAFV600E mutation was 81.4% (323/397) in patients with a solitary
PTC. Univariate analyses showed that BRAFV600E mutation was significantly
associated with margin, higher ACR TI-RADS point scores, and Hashimoto's
thyroiditis. In multivariate analyses, lobulated or irregular margin was
independently associated with BRAFV600E mutation in total solitary PTC.
Furthermore, both in total solitary PTC and papillary thyroid microcarcinoma,
BRAFV600E mutation was associated with ACR TI-RADS point scores, which was
positively correlated with the risk of BRAFV600E mutation. There was no
significant relationship between BRAFV600E mutation and ACR TI-RADS point scores
in PTC >10mm. In addition, Hashimoto's thyroiditis had a significant negative
association with BRAFV600E mutation. CONCLUSION: A lobulated or irregular margin
of the thyroid nodule is independently associated with BRAFV600E mutation in
patients with PTC. In addition, higher ACR TI-RADS point scores is an independent
risk factor for BRAFV600E mutation, and ACR TI-RADS point scores is positively
associated with the risk of BRAFV600E mutation in solitary PTC, especially in
papillary thyroid microcarcinoma. Our findings may be helpful for preoperative
identification and medical management of PTC patients with BRAFV600E mutation.
PMID- 29941399
TI - Radiology Residency Match: The Cost of Being in the Dark.
AB - RATIONALE AND OBJECTIVES: The Electronic Resident Application Service (ERAS)
publishes monthly statistics before the match and the National Resident Matching
Program publishes the match outcomes. We sought to determine whether early ERAS
data influences applicant behavior and correlates with match outcomes. MATERIALS
AND METHODS: We searched the 2007-2017 ERAS archives for the applicant pool size
(PS), the average number of applications per program (AP), and the average number
of applications per applicant (AA) in November, before radiology match, and the
2007-2017 National Resident Matching Program archives for the average number of
ranked applicants needed to fill each position (ANRA) and the number of unfilled
positions (UP) in radiology match. Correlation coefficients were calculated for
each pair. RESULTS: PS correlated very strongly with AP (r = 0.80, p = 0.001708),
UP (r = -0.92, p = 0.000063) and ANRA (r = -0.90, p = 0.000164). UP correlated
strongly with ANRA (r = 0.76, p = 0.006349) and AP (r = -0.77, p = 0.005339). A
trend to moderate correlation between AP and ANRA (r = 0.58, p = 0.062686) and AA
(r = 0.53, p = 0.074395) did not reach statistical significance. There was no
correlation between AA and PS in the same (r = -0.05, p = 0.878585) or the
following year (r = 0.35, p = 0.297166), and AA and UP in the same (r = 0.13, p =
0.701983) or the following year (r = 0.32, p = 0.336136). CONCLUSION: The real
time data reported by ERAS in November, before match, is a predictor of radiology
match outcomes and can be used by all participants to limit their application and
recruitment costs. Medical students applying to radiology do not consider either
the real-time or historic data when submitting ERAS applications.
PMID- 29941400
TI - Chronic myelogenous leukemia presenting with osteonecrosis of the jaw as a rare
but debilitating toxicity of dasatinib: a case report and literature review.
AB - This report describes a case of osteonecrosis of the jaw developing after a
routine dental extraction in a patient being treated with dasatinib, a tyrosine
kinase inhibitor, for chronic myelogenous leukemia. As the role of tyrosine
kinase inhibitors in cancer treatment expands, patterns of debilitating
complications involving the osseous structures of the oral cavity have begun to
emerge, and many long-term side effects of this promising therapy remain unknown.
To limit the occurrence of known complications, health care providers and
patients must be aware of the potential for serious complications of dasatinib,
and appropriate protocols should be in place before administration of this
medication.
PMID- 29941401
TI - Primary intestinal-type adenocarcinoma of the buccal mucosa: A case report and
literature review.
AB - Intestinal-type adenocarcinoma of the primary salivary glands is extremely rare.
So far, only 11 cases of primary intestinal-type adenocarcinoma of the oral
cavity and major salivary glands have been reported. Two of those tumors arose in
the floor of mouth, 7 in the tongue, and 2 in the major salivary glands. However,
it has remained unclear whether these tumors are derived from mature salivary
glands, and primary intestinal-type adenocarcinoma of the buccal mucosa has not
been reported previously. Here, we present the first documented case of primary
intestinal-type adenocarcinoma arising in a minor salivary gland of the buccal
mucosa. Histopathologically, the tumor resembled a well-differentiated or
mucinous colonic adenocarcinoma. Immunohistochemically, the tumor cells were
diffusely positive for AE1/AE3, CAM5.2, CK7, SATB2, beta-catenin, p53, Ki-67,
MUC2, and MUC5 AC. CK14 and CK20 were positive in some of the tumor cells. CDX2,
CA19-9, SP-A, TTF-1, PSA, SMA, p63, and cyclin D1 were negative in the tumor
cells. The tumor in the present case may have originated from salivary gland duct
epithelium that underwent transformation to phenotypic intestinal-type
epithelium. In this very rare case of primary intestinal-type adenocarcinoma of
the buccal mucosa, we considered diagnostic markers that could be indicative of
mature salivary gland origin.
PMID- 29941402
TI - A randomized controlled study to evaluate an experimental moisturizing mouthwash
formulation in participants experiencing dry mouth symptoms.
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of
an experimental moisturizing mouthwash versus water only in participants
experiencing dry mouth symptoms, including those with Sjogren syndrome (n = 28).
STUDY DESIGN: Participants were randomized to the experimental mouthwash group (n
= 53) or the water-only group (n = 47). For 8 days, the mouthwash group used 1 to
2 doses/day at home; both groups could sip water, as needed. Supervised treatment
occurred on days 1, 3, and 8, and during this treatment, before and after
administration, participants completed the Product Performance and Attributes
Questionnaire parts 1 through 4. RESULTS: Significant between-treatment
differences on all Product Performance and Attributes Questionnaire questions
were shown at most time points. On day 8, at 120 minutes, there was a significant
difference on Product Performance and Attributes Questionnaire 3-Question 1
("Relieves the discomfort of dry mouth"; the predefined primary efficacy
variable) in favor of mouthwash versus water (0.63 [95% confidence interval 0.17
1.10]; P = .0084). Subgroup analysis found a significant difference that favored
mouthwash in participants without Sjogren syndrome (0.67 [0.11,1.23]; P = .0203)
but not with Sjogren syndrome (0.52 [-0.35,1.38; P = .2272). Eight, non-serious,
oral treatment-related adverse events were reported by the mouthwash group.
CONCLUSIONS: The findings of a subjective questionnaire showed that an
experimental moisturizing mouthwash provided greater relief than water only from
dry mouth symptoms over 8 days.
PMID- 29941403
TI - A qualitative study of stakeholder views and experiences of minor ailment
services in the United Kingdom.
AB - BACKGROUND: An international strategy designed to promote access to primary care
is the utilisation of community pharmacy to deliver structured minor ailment
services (MASs). An understanding of key implementation features of MASs will
support effective service delivery and implementation, promote MAS viability,
sustainability and overall improvement. AIM: The aim of this study is to explore
the views and experiences of a range of stakeholders concerning the
implementation of MASs in the United Kingdom. METHODS: A qualitative approach was
used to obtain data. Participants were recruited using purposeful and snowball
sampling. Stakeholders from five different regions were included. Using the
digital recordings of the interviews, thematic content analysis was undertaken.
RESULTS: Thirty-three participants agreed to be interviewed. Twenty-nine semi
structured interviews were conducted. Thematic content analysis yielded three
major themes, including (1) benefits of MASs, (2) structural challenges
associated with MAS design and (3) other implementation factors associated with
MAS delivery. Stakeholders recognised the positive impact of the service to
improve patient access and care, promote efficiencies, and promote the
professional role of the pharmacist. Nevertheless barriers do exist to service
delivery and implementation. Stakeholders identified the need to potentially
increase the population groups served by MASs, increase the conditions treated
and widen their formulary lists. Similarly, marketing strategies needed to be
improved to enhance consumer awareness. Stakeholders presented mixed views about
whether pharmacists needed to complete clinical training and the need to increase
pharmacist's remuneration. In addition the level of healthcare collaboration
needed to improve. CONCLUSION: Several concepts emerged from the investigation to
facilitate service delivery. Barriers to service implementation had a variable
impact on implementation. Service delivery should function to meet all
stakeholder needs and can be achieved through stakeholder collaboration. However,
improved marketing to promote consumer awareness together with better
collaborative processes can potentially improve MAS implementation.
PMID- 29941404
TI - Pharmacists' learning needs in the era of expanding scopes of practice: Evolving
practices and changing needs.
AB - BACKGROUND: Continuing professional development fosters advancement in knowledge
and skills and can support changes in practice. Research suggests that
pharmacists perceive the need for additional training to take on expanded roles.
However, the types of professional development and preferred learning methods are
unclear. OBJECTIVE: To identify pharmacists' professional learning needs in order
to support expanded roles in practice. METHODS: A mixed-methods approach was
used. In focus groups made up of pharmacists and pharmacy students, learning
needs associated with their perceptions of pharmacists' roles were examined. A
web-based survey of Albertan pharmacists determined the knowledge, experience,
and confidence required to engage in professional activities, preferred learning
methods, and professional development needed to support pharmacists currently and
in future. RESULTS: Analysis of data obtained from 5 focus groups (n = 42)
revealed learning needs related to changes in pharmacists' roles. Pharmacists
valued the social aspect of learning as well as the role of certification in
building confidence. Survey data (n = 416) indicated that a high proportion of
pharmacists reported training needs in the areas of physical assessment,
interpreting laboratory tests, and making decisions about complex drug therapy.
Community pharmacists and those with bachelor degrees were more likely to
indicate a need for additional training in various patient care skills.
Pharmacists reported a preference for learning with peers and learning at work
within teams. CONCLUSION: Meeting various learning needs will foster pharmacists
in their current and future professional roles, including situated learning in
the workplace. These findings will be of interest to employers and educators in
supporting pharmacists' evolving roles in practice.
PMID- 29941405
TI - Serum fascin autoantibodies level for esophageal squamous cell carcinoma
diagnosis.
PMID- 29941406
TI - Correction to Lancet HIV 2018; DOI:10.1016/S2352-3018(18)30092-4.
PMID- 29941407
TI - Angiosarcoma associated with hypertrichosis.
PMID- 29941408
TI - Rehospitalization following a stay in geriatric rehabilitation wards: rates and
predictive factors.
AB - : Hospitalization in the elderly patients is highly associated with morbi
mortality. Geriatric post-acute and rehabilitation care wards are designed to
provide care and to implement life project of elderly patients. Objective of this
study was to characterize rehospitalizations after a stay in geriatric post-acute
and rehabilitation care wards. METHODS: The study was retrospective, case
control, including all the patients hospitalized in the 4 geriatric post-acute
and rehabilitation care wards of a hospital in Paris (France) and returned at
home. Data collection was carried out on the basis of the hospitalization report
and the information system of the hospital. Rehospitalizations were documented by
the information system as well as by telephone interview. We compared patients
according to whether they had been rehospitalized or not within 60 days after
discharge. RESULTS: Out of a total of 1,063 stays during a 12 months period, 435
(41%) were discharged at home. Re-admission rate was 10.1% at 30 days and 18.4%
at 90 days. Mean age of rehospitaliszed patients was 87.2 years +/- 5.3 vs 87.9
years +/- 5.8 for non-rehospitalized patients. Patients rehospitalized had more
often a delirium during the prior hospitalization. CONCLUSION: Unplanned
rehospitalisation is a major public health issue and should be prevented
particularly after a stay in a geriatric post-acute and rehabilitation care
wards.
PMID- 29941409
TI - Subungual melanoma complicated by hydroxyurea-induced melanonychia with non
melanoma Hutchinson's sign.
PMID- 29941410
TI - Takayasu arteritis revealed by unusual cutaneous manifestations.
PMID- 29941411
TI - Contact vitiligo induced by rubber ear loops from a disposable sanitary mask.
PMID- 29941412
TI - Successful Daylight-PDT using a self-adhesive 5-aminolaevulinic acid patch.
PMID- 29941413
TI - The benefits of high-resolution, real-time colour-imaging of lymphatic flow for
sentinel lymph node biopsy.
PMID- 29941414
TI - Psoriatic mesenchymal stem cells demonstrate an enhanced ability to differentiate
into vascular endothelial cells.
PMID- 29941415
TI - A Deep Learning Method to Automatically Identify Reports of Scientifically
Rigorous Clinical Research from the Biomedical Literature: Comparative Analytic
Study.
AB - BACKGROUND: A major barrier to the practice of evidence-based medicine is
efficiently finding scientifically sound studies on a given clinical topic.
OBJECTIVE: To investigate a deep learning approach to retrieve scientifically
sound treatment studies from the biomedical literature. METHODS: We trained a
Convolutional Neural Network using a noisy dataset of 403,216 PubMed citations
with title and abstract as features. The deep learning model was compared with
state-of-the-art search filters, such as PubMed's Clinical Query Broad treatment
filter, McMaster's textword search strategy (no Medical Subject Heading, MeSH,
terms), and Clinical Query Balanced treatment filter. A previously annotated
dataset (Clinical Hedges) was used as the gold standard. RESULTS: The deep
learning model obtained significantly lower recall than the Clinical Queries
Broad treatment filter (96.9% vs 98.4%; P<.001); and equivalent recall to
McMaster's textword search (96.9% vs 97.1%; P=.57) and Clinical Queries Balanced
filter (96.9% vs 97.0%; P=.63). Deep learning obtained significantly higher
precision than the Clinical Queries Broad filter (34.6% vs 22.4%; P<.001) and
McMaster's textword search (34.6% vs 11.8%; P<.001), but was significantly lower
than the Clinical Queries Balanced filter (34.6% vs 40.9%; P<.001). CONCLUSIONS:
Deep learning performed well compared to state-of-the-art search filters,
especially when citations were not indexed. Unlike previous machine learning
approaches, the proposed deep learning model does not require feature
engineering, or time-sensitive or proprietary features, such as MeSH terms and
bibliometrics. Deep learning is a promising approach to identifying reports of
scientifically rigorous clinical research. Further work is needed to optimize the
deep learning model and to assess generalizability to other areas, such as
diagnosis, etiology, and prognosis.
PMID- 29941416
TI - Interactive Visual Displays for Interpreting the Results of Clinical Trials:
Formative Evaluation With Case Vignettes.
AB - BACKGROUND: At the point of care, evidence from randomized controlled trials
(RCTs) is underutilized in helping clinicians meet their information needs.
OBJECTIVE: To design interactive visual displays to help clinicians interpret and
compare the results of relevant RCTs for the management of a specific patient,
and to conduct a formative evaluation with physicians comparing interactive
visual versus narrative displays. METHODS: We followed a user-centered and
iterative design process succeeded by development of information display
prototypes as a Web-based application. We then used a within-subjects design with
20 participants (8 attendings and 12 residents) to evaluate the usability and
problem-solving impact of the information displays. We compared subjects'
perceptions of the interactive visual displays versus narrative abstracts.
RESULTS: The resulting interactive visual displays present RCT results side-by
side according to the Population, Intervention, Comparison, and Outcome (PICO)
framework. Study participants completed 19 usability tasks in 3 to 11 seconds
with a success rate of 78% to 100%. Participants favored the interactive visual
displays over narrative abstracts according to perceived efficiency,
effectiveness, effort, user experience and preference (all P values <.001).
CONCLUSIONS: When interpreting and applying RCT findings to case vignettes,
physicians preferred interactive graphical and PICO-framework-based information
displays that enable direct comparison of the results from multiple RCTs compared
to the traditional narrative and study-centered format. Future studies should
investigate the use of interactive visual displays to support clinical decision
making in care settings and their effect on clinician and patient outcomes.
PMID- 29941417
TI - Effectiveness of a Text Messaging-Based Intervention Targeting Alcohol
Consumption Among University Students: Randomized Controlled Trial.
AB - BACKGROUND: Excessive drinking among university students is a global challenge,
leading to significant health risks. However, heavy drinking among students is
widely accepted and socially normalized. Mobile phone interventions have
attempted to reach students who engage in excessive drinking. A growing number of
studies suggest that text message-based interventions could potentially reach
many students and, if effective, such an intervention might help reduce heavy
drinking in the student community. OBJECTIVE: The objective of this study was to
test the effectiveness of a behavior change theory-based 6-week text message
intervention among university students. METHODS: This study was a two-arm,
randomized controlled trial with an intervention group receiving a 6-week text
message intervention and a control group that was referred to treatment as usual
at the local student health care center. Outcome measures were collected at
baseline and at 3 months after the initial invitation to participate in the
intervention. The primary outcome was total weekly alcohol consumption. Secondary
outcomes were frequency of heavy episodic drinking, highest estimated blood
alcohol concentration, and number of negative consequences attributable to
excessive drinking. RESULTS: A total of 896 students were randomized to either
the intervention or control group. The primary outcome analysis included 92.0% of
the participants in the intervention group and 90.1% of the control group. At
follow-up, total weekly alcohol consumption decreased in both groups, but no
significant between-group difference was seen. Data on the secondary outcomes
included 49.1% of the participants in the intervention group and 41.3% of the
control group. No significant between-group difference was seen for any of the
secondary outcomes. CONCLUSIONS: The present study was under-powered, which could
partly explain the lack of significance. However, the intervention, although
theory-based, needs to be re-assessed and refined to better support the target
group. Apart from establishing which content forms an effective intervention, the
optimal length of an alcohol intervention targeting students also needs to be
addressed in future studies. TRIAL REGISTRATION: International Standard
Randomised Controlled Trial Number ISRCTN95054707;
http://www.isrctn.com/ISRCTN95054707 (Archived by WebCite at
http://www.webcitation.org/70Ax4vXhd).
PMID- 29941418
TI - Prospective Epidemiological Research on Functioning Outcomes Related to Major
Depressive Disorder in Japan (PERFORM-J): Protocol for a Prospective Cohort
Study.
AB - BACKGROUND: Patients with major depressive disorder may exhibit cognitive
dysfunction that can affect functional outcomes. However, the prevalence and
burden of cognitive dysfunction in Japanese patients with MDD have not been
thoroughly examined. OBJECTIVE: To investigate the time course (over 6 months) of
several functional outcomes during treatment with antidepressants in Japanese
patients with major depressive disorder. The primary objective is to assess
longitudinal changes in cognitive function and depressive symptoms, using both
clinician-rated and patient-rated scales. The study incorporates assessments of
cognitive function and other functional outcomes (functional capacity,
disability, work productivity and impairments of activity, and quality of life),
as well as depressive symptoms. METHODS: PERFORM-J (Prospective Epidemiological
Research on Functioning Outcomes Related to Major Depressive Disorder in Japan)
is a 6-month, prospective, multi-center, epidemiological cohort study.
Participants are Japanese outpatients aged 18-65 years with a recurrent or new
diagnosis of a major depressive episode (according to the Diagnostic and
Statistical Manual of Mental Disorders, 4th Edition, Text Revision [DSM-IV-TR]),
who are initiating a new antidepressant as monotherapy (either as first-line
therapy or after switching from a previous antidepressant). Eligible patients are
evaluated objectively during four visits (at baseline and at Months 1, 2, and 6)
using physician-rated assessments of severity of depressive symptoms, cognitive
function, and functional capacity. Subjective, patient-reported, outcomes are
also assessed as indicators of depressive symptoms, disability, work productivity
or impairments of activity, and perceived cognitive dysfunction. RESULTS: The
study began in September 2016. Patient enrollment was completed on June 30, 2017,
with 523 patients having been enrolled from 48 study sites. As of October, 2017,
279 patients had completed the study. CONCLUSIONS: PERFORM-J is expected to
provide valuable information on the longitudinal relationship between cognitive
dysfunction, depressive symptoms, and other functional outcomes in Japanese
patients with major depressive disorder who initiate monotherapy with
antidepressants. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000024320;
https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000028011
(Archived by WebCite at http://www.webcitation.org/70K7W9PgC). REGISTERED REPORT
IDENTIFIER: RR1-10.2196/9682.
PMID- 29941420
TI - Five minutes with . . . Harold Ellis.
PMID- 29941419
TI - Efficacy of Acceptance and Commitment Therapy in Reducing Suicidal Ideation and
Deliberate Self-Harm: Systematic Review.
AB - BACKGROUND: Since its emergence in the 1980s, acceptance and commitment therapy
(ACT) has become a reputable evidence-based psychological therapy for certain
disorders. Trials examining the efficacy of ACT are spread across a broad
spectrum of presentations, such as chronic pain, anxiety, and depression.
Nevertheless, ACT has very rarely been trialed as an intervention for suicidal
ideation (SI) or deliberate self-harm (DSH). OBJECTIVE: The objective of this
review is to assess the efficacy of ACT in reducing SI and DSH and to examine the
suitability of reported SI, DSH, and other measures in determining the efficacy
of ACT. METHODS: We systematically reviewed studies on ACT as intervention for SI
and self-harm. Electronic databases, including MEDLINE, PubMed, EMBASE, PsycINFO,
SCOPUS, Cochrane Central Register of Controlled Trials, and the Cochrane Database
of Systematic Reviews, were searched. The reference lists of included studies and
relevant systematic reviews were examined to identify additional publications.
Search terms were identified with reference to the terminology used in previous
review papers on ACT and suicide prevention. The study design was not restricted
to randomized controlled trials. Screening was completed by 2 reviewers, and all
duplicates were removed. Publications were excluded if they were not published in
English, were multicomponent therapy or were not based on ACT, or lacked a
validated measure or structured reporting of SI/DSH outcomes. RESULTS: After
removing the duplicates, 554 articles were screened for relevance. Following the
screening, 5 studies that used ACT as an intervention for suicidal or self
harming individuals were identified. The studies used diverse methodologies and
included 2 case studies, 2 pre-post studies, and 1 mHealth randomized controlled
trial. CONCLUSIONS: The review found that ACT is effective in reducing SI in the
2 pre-post studies but not in other studies. However, given the small number and
lack of methodological rigor of the studies included in this review, insufficient
evidence exists for the recommendation of ACT as an intervention for SI or DSH.
PMID- 29941421
TI - Stress-Induced, Highly Efficient, Donor Cell-Dependent Cell-to-Cell Natural
Transformation in Bacillus subtilis.
AB - Horizontal gene transfer (HGT) is a driving force for bacterial evolution that
occurs via conjugation, transduction, and transformation. Whereas conjugation and
transduction depend on nonbacterial vehicles, transformation is considered a
naturally occurring process in which naked DNA molecules are taken up by a
competent recipient cell. Here, we report that HGT occurred between two Bacillus
subtilis strains cocultured on a minimum medium agar plate for 10 h. This process
was almost completely resistant to DNase treatment and appeared to require close
proximity between cells. The deletion of comK in the recipient completely
abolished gene transfer, indicating that the process involved transformation.
This process was also highly efficient, reaching 1.75 * 106 transformants/MUg DNA
compared to 5.3 * 103 and 1.86 * 105 transformants/MUg DNA for DNA-to-cell
transformation by the same agar method and the standard two-step procedure,
respectively. Interestingly, when three distantly localized chromosomal markers
were selected simultaneously, the efficiency of cell-to-cell transformation still
reached 6.26 * 104 transformants/MUg DNA, whereas no transformants were obtained
when free DNA was used as the donor. Stresses, such as starvation and exposure to
antibiotics, further enhanced transformation efficiency by affecting the donor
cells, suggesting that stress served as an important signal for promoting this
type of HGT. Taken together, our results defined a bona fide process of cell-to
cell natural transformation (CTCNT) in B. subtilis and related species. This
finding reveals the previously unrecognized role of donor cells in bacterial
natural transformation and improves our understanding of how HGT drives bacterial
evolution at a mechanistic level.IMPORTANCE Because DNA is easily prepared,
studies of bacterial natural genetic transformation traditionally focus on
recipient cells. However, such laboratory artifacts cannot explain how this
process occurs in nature. In most cases, competence is only transient and
involves approximately 20 to 50 genes, and it is unreasonable for bacteria to
spend so many genetic resources on unpredictable and uncertain environmental DNA.
Here, we characterized a donor cell-dependent CTCNT process in B. subtilis and
related species that was almost completely resistant to DNase treatment and was
more efficient than classical natural transformation using naked DNA as a donor,
i.e., DNA-to-cell transformation, suggesting that DNA donor cells were also
important in the transformation process in natural environments.
PMID- 29941422
TI - Influence of Origin Recognition Complex Proteins on the Copy Numbers of Three
Chromosomes in Haloferax volcanii.
AB - Replication initiation in archaea involves a protein named ORC, Cdc6, or
ORC1/Cdc6, which is homologous to the eukaryotic origin recognition complex (ORC)
proteins and to the eukaryotic Cdc6. Archaeal replication origins are comprised
of origin repeat regions and adjacent orc genes. Some archaea contain a single
replication origin and a single orc gene, while others have more than one of
each. Haloferax volcanii is exceptional because it contains, in total, six
replication origins on three chromosomes and 16 orc genes. Phylogenetic trees
were constructed that showed that orc gene duplications occurred at very
different times in evolution. To unravel the influence of the ORC proteins on
chromosome copy number and cellular fitness, it was attempted to generate
deletion mutants of all 16 genes. A total of 12 single-gene deletion mutants
could be generated, and only three orc gene turned out to be essential. For one
gene, the deletion analysis failed. Growth analyses revealed that no deletion
mutant had a growth defect, but some had a slight growth advantage compared to
the wild type. Quantification of the chromosome copy numbers in the deletion
mutants showed that all 12 ORC proteins influenced the copy numbers of one, two,
or all three chromosomes. The lack of an ORC led to an increase or decrease of
chromosome copy number. Therefore, chromosome copy numbers in Hfxvolcanii are
regulated by an intricate network of ORC proteins. This is in contrast to other
archaea, in which ORC proteins typically bind specifically to the adjacent
origin.IMPORTANCE The core origins of archaea are comprised of a repeat region
and an adjacent gene for an origin recognition complex (ORC) protein, which is
homologous to eukaryotic ORC proteins. Haloferax volcanii is exceptional because
it contains six replication origins on three chromosomes and an additional 10 orc
genes that are not adjacent to an origin. This unique ORC protein repertoire was
used to unravel the importance of core origin orc genes and of origin-remote orc
genes. Remarkably, all ORC proteins influenced the copy number of at least one
chromosome. Some of them influenced those of all three chromosomes, showing that
cross-regulation in trans exists in Hfx. volcanii Furthermore, the evolution of
the archaeal ORC protein family was analyzed.
PMID- 29941423
TI - Regulatory Properties of the ADP-Glucose Pyrophosphorylase from the Clostridial
Firmicutes Member Ruminococcus albus.
AB - ADP-glucose pyrophosphorylase from Firmicutes is encoded by two genes (glgC and
glgD) leading to a heterotetrameric protein structure, unlike those in other
bacterial phyla. The enzymes from two groups of Firmicutes, Bacillales and
Lactobacillales, present dissimilar kinetic and regulatory properties.
Nevertheless, no ADP-glucose pyrophosphorylase from Clostridiales, the third
group in Firmicutes, has been characterized. For this reason, we cloned the glgC
and glgD genes from Ruminococcus albus Different quaternary forms of the enzyme
(GlgC, GlgD, and GlgC/GlgD) were purified to homogeneity and their kinetic
parameters were analyzed. We observed that GlgD is an inactive monomer when
expressed alone but increased the catalytic efficiency of the heterotetramer
(GlgC/GlgD) compared to the homotetramer (GlgC). The heterotetramer is regulated
by fructose-1,6-bisphosphate, phosphoenolpyruvate, and NAD(P)H. The first
characterization of the Bacillales enzyme suggested that heterotetrameric ADP
glucose pyrophosphorylases from Firmicutes were unregulated. Our results,
together with data from Lactobacillales, indicate that heterotetrameric
Firmicutes enzymes are mostly regulated. Thus, the ADP-glucose pyrophosphorylase
from Bacillales seems to have distinctive insensitivity to regulation.IMPORTANCE
The enzymes involved in glycogen synthesis from Firmicutes have been less
characterized in comparison with other bacterial groups. We performed kinetic and
regulatory characterization of the ADP-glucose pyrophosphorylase from
Ruminococcus albus Our results showed that this protein that belongs to different
groups from Firmicutes (Bacillales, Lactobacillales, and Clostridiales) presents
dissimilar features. This study contributes to the understanding of how this
critical enzyme for glycogen biosynthesis is regulated in the Firmicutes group,
whereby we propose that these heterotetrameric enzymes, with the exception of
Bacillales, are allosterically regulated. Our results provide a better
understanding of the evolutionary relationship of this enzyme family in
Firmicutes.
PMID- 29941424
TI - MsaB and CodY Interact To Regulate Staphylococcus aureus Capsule in a Nutrient
Dependent Manner.
AB - Staphylococcus aureus has a complex regulatory network for controlling the
production of capsule polysaccharide. In S. aureus, capsule production is
controlled by several regulators in response to various environmental stimuli.
Previously, we described MsaB as a new regulator that specifically binds to the
cap promoter in a growth phase- or nutrient-dependent manner. In addition to
MsaB, several other regulators have also been shown to bind the same region. In
this study, we examined the interactions between MsaB and other nutrient-sensing
regulators (CodY and CcpE) with respect to binding to the cap promoter in a
nutrient-dependent manner. We observed that msaABCR and ccpE interact in a
complex fashion to regulate capsule production. However, we confirmed that ccpE
does not bind cap directly. We also defined the regulatory relationship between
msaABCR and CodY. When nutrients (branched-chain amino acids) are abundant, CodY
binds to the promoter region of the cap operon and represses its transcription.
However, when nutrient concentrations decrease, MsaB, rather than CodY, binds to
the cap promoter. Binding of MsaB to the cap promoter activates transcription of
the cap operon. We hypothesize that this same mechanism may be used by S. aureus
to regulate other virulence factors.IMPORTANCE Findings from this study define
the mechanism of regulation of capsule production in Staphylococcus aureus
Specifically, we show that two key regulators, MsaB and CodY, coordinate their
functions to control the expression of capsule in response to nutrients. S.
aureus fine-tunes the production of capsule by coordinating the activity of
several regulators and by sensing nutrient levels. This study demonstrates the
importance of incorporating multiple inputs prior to the expression of costly
virulence factors, such as capsule.
PMID- 29941425
TI - A Genetic Determinant of Persister Cell Formation in Bacterial Pathogens.
AB - Persisters represent a small subpopulation of cells within a bacterial culture
that are tolerant to killing by antibiotics. Persisters have been linked to
recalcitrant infections caused by numerous bacterial pathogens, including
Pseudomonas aeruginosa A classic example is the incurable infection of the
airways for patients with cystic fibrosis. The genetic mediators of persister
formation for P. aeruginosa are poorly understood. We generated a high-density
transposon insertion library of P. aeruginosa PAO1 and determined the relative
frequency of each insertion following fluoroquinolone treatment using transposon
sequencing (Tn-seq). Of the 4,411 disrupted genes included in the screen, 137 had
a >=10-fold impact on survival. The gene disruption that resulted in the lowest
survival rate was disruption of carB, which codes for the large subunit of
carbamoyl phosphate synthetase (CPSase). CPSase is a metabolic enzyme that is
involved in pyrimidine and arginine synthesis. Disruption of carB resulted in
survival rates that were reduced by up to 2,500-fold following antibiotic
treatment, and this phenotype was abolished by the addition of uracil,
highlighting the importance of de novo pyrimidine biosynthesis for persister
formation. Disruption of carB resulted in intracellular ATP accumulation, and
lowering ATP levels using arsenate restored the antibiotic tolerance profile of
the mutant to levels similar to those seen with the wild type. A decrease in ATP
would lead to reduced antibiotic target activity and increased
survival.IMPORTANCE Antibiotic treatment of P. aeruginosa residing in the lung of
cystic fibrosis patients is ineffective. Treatment failure is attributed in part
to antibiotic-tolerant phenotypic variants known as persister cells.
Understanding how these cells emerge will likely inform future therapeutic
strategies. In the current study, we identified carB, which codes for the large
subunit of carbamoyl-phosphate synthetase, as a persister gene that contributes
to multidrug tolerance in P. aeruginosa Disruption of carB resulted in a
metabolic perturbation that increased cellular ATP and reduced persister
formation. Conversely, lowering ATP in the mutant restored antibiotic tolerance.
Our data support the hypothesis that a drop in intracellular ATP is a general
mechanism of persister formation in bacteria.
PMID- 29941427
TI - Changing epidemiology of assault victims in an emergency department participating
in information sharing with police: a time series analysis.
AB - INTRODUCTION: Violent injury places a large burden on the NHS. We had implemented
information sharing in our ED in 2007 and aimed to see which patient groups were
most affected by information sharing, as this would provide clues as to how this
complex intervention works. METHODS: Retrospective time series study of all the
assault victims presenting for ED care between 2005 and 2014 at a single ED in
England. RESULTS: 10 328 patients presented during the study period. There was a
37% decrease in the number of patients presenting after assault, consistent with
national trends. The proportions of people arriving by ambulance, and the
proportion of men did not change during the study period. There were no important
changes in the age of our assault patients in this study. Greater,
disproportionate, decreases in rates of violence were seen in patients who
presented at the weekend up (incidence rate ratio (IRR)=0.57, 95% CI 0.50 to
0.64) versus weekdays (IRR=0.72; 95% CI 0.62 to 0.83) There were also
disproportionately greater decreases over the study period in patients who were
discharged with no hospital follow-up (IRR=0.51, 95% CI 0.45 to 0.56) versus
those leading to either an inpatient admission (IRR=1.05, 95% CI 0.84 to 1.31) or
outpatient follow-up (IRR=1.23, 95% CI 0.93 to 1.64). CONCLUSIONS: The
epidemiology of violent injury at our institution has changed over the last 10
years and is most marked in a reduction of visits at the weekend, and in those
who leave without follow up.
PMID- 29941426
TI - Biological classification with RNA-seq data: Can alternatively spliced transcript
expression enhance machine learning classifiers?
AB - RNA sequencing (RNA-seq) is becoming a prevalent approach to quantify gene
expression and is expected to gain better insights into a number of biological
and biomedical questions compared to DNA microarrays. Most importantly, RNA-seq
allows us to quantify expression at the gene or transcript levels. However,
leveraging the RNA-seq data requires development of new data mining and analytics
methods. Supervised learning methods are commonly used approaches for biological
data analysis that have recently gained attention for their applications to RNA
seq data. Here, we assess the utility of supervised learning methods trained on
RNA-seq data for a diverse range of biological classification tasks. We
hypothesize that the transcript-level expression data are more informative for
biological classification tasks than the gene-level expression data. Our large
scale assessment utilizes multiple data sets, organisms, lab groups, and RNA-seq
analysis pipelines. Overall, we performed and assessed 61 biological
classification problems that leverage three independent RNA-seq data sets and
include over 2000 samples that come from multiple organisms, lab groups, and RNA
seq analyses. These 61 problems include predictions of the tissue type, sex, or
age of the sample, healthy or cancerous phenotypes, and pathological tumor stages
for the samples from the cancerous tissue. For each problem, the performance of
three normalization techniques and six machine learning classifiers was explored.
We find that for every single classification problem, the transcript-based
classifiers outperform or are comparable with gene expression-based methods. The
top-performing techniques reached a near perfect classification accuracy,
demonstrating the utility of supervised learning for RNA-seq based data analysis.
PMID- 29941428
TI - Genomewide phenotypic analysis of growth, cell morphogenesis, and cell cycle
events in Escherichia coli.
AB - Cell size, cell growth, and cell cycle events are necessarily intertwined to
achieve robust bacterial replication. Yet, a comprehensive and integrated view of
these fundamental processes is lacking. Here, we describe an image-based
quantitative screen of the single-gene knockout collection of Escherichia coli
and identify many new genes involved in cell morphogenesis, population growth,
nucleoid (bulk chromosome) dynamics, and cell division. Functional analyses,
together with high-dimensional classification, unveil new associations of
morphological and cell cycle phenotypes with specific functions and pathways.
Additionally, correlation analysis across ~4,000 genetic perturbations shows that
growth rate is surprisingly not predictive of cell size. Growth rate was also
uncorrelated with the relative timings of nucleoid separation and cell
constriction. Rather, our analysis identifies scaling relationships between cell
size and nucleoid size and between nucleoid size and the relative timings of
nucleoid separation and cell division. These connections suggest that the
nucleoid links cell morphogenesis to the cell cycle.
PMID- 29941429
TI - "Illogical" cannabis regulation blocks research into therapeutic uses, say
doctors.
PMID- 29941431
TI - A forward genetic screen identifies chaperone CNX-1 as a conserved biogenesis
regulator of ERG K+ channels.
AB - The human ether-a-go-go-related gene (hERG) encodes a voltage-gated potassium
channel that controls repolarization of cardiac action potentials. Accumulating
evidence suggests that most disease-related hERG mutations reduce the function of
the channel by disrupting protein biogenesis of the channel in the endoplasmic
reticulum (ER). However, the molecular mechanism underlying the biogenesis of ERG
K+ channels is largely unknown. By forward genetic screening, we identified an ER
located chaperone CNX-1, the worm homologue of mammalian chaperone Calnexin, as a
critical regulator for the protein biogenesis of UNC-103, the ERG-type K+ channel
in Caenorhabditis elegans Loss-of-function mutations of cnx-1 decreased the
protein level and current density of the UNC-103 K+ channel and suppressed the
behavioral defects caused by a gain-of-function mutation in unc-103 Moreover, CNX
1 facilitated tetrameric assembly of UNC-103 channel subunits in a liposome
assisted cell-free translation system. Further studies showed that CNX-1 act in
parallel to DNJ-1, another ER-located chaperone known to regulate maturation of
UNC-103 channels, on controlling the protein biogenesis of UNC-103. Importantly,
Calnexin interacted with hERG proteins in the ER in HEK293T cells. Deletion of
calnexin reduced the expression and current densities of endogenous hERG K+
channels in SH-SY5Y cells. Collectively, we reveal an evolutionarily conserved
chaperone CNX-1/Calnexin controlling the biogenesis of ERG-type K+ channels.
PMID- 29941433
TI - Euglycemic diabetic ketoacidosis associated with the use of a sodium-glucose
cotransporter-2 inhibitor.
PMID- 29941430
TI - Gating currents.
AB - Many membrane proteins sense the voltage across the membrane where they are
inserted, and their function is affected by voltage changes. The voltage sensor
consists of charges or dipoles that move in response to changes in the electric
field, and their movement produces an electric current that has been called
gating current. In the case of voltage-gated ion channels, the kinetic and steady
state properties of the gating charges provide information of conformational
changes between closed states that are not visible when observing ionic currents
only. In this Journal of General Physiology Milestone, the basic principles of
voltage sensing and gating currents are presented, followed by a historical
description of the recording of gating currents. The results of gating current
recordings are then discussed in the context of structural changes in voltage
dependent membrane proteins and how these studies have provided new insights on
gating mechanisms.
PMID- 29941434
TI - Adnexal torsion.
PMID- 29941432
TI - The evolving epidemiology of Clostridium difficile infection in Canadian
hospitals during a postepidemic period (2009-2015).
AB - BACKGROUND: The clinical and molecular epidemiology of health care-associated
Clostridium difficile infection in nonepidemic settings across Canada has evolved
since the first report of the virulent North American pulsed-field gel
electrophoresis type 1 (NAP1) strain more than 15 years ago. The objective of
this national, multicentre study was to describe the evolving epidemiology and
molecular characteristics of health care-associated C. difficile infection in
Canada during a post-NAP1-epidemic period, particularly patient outcomes
associated with the NAP1 strain. METHODS: Adult inpatients with C. difficile
infection were prospectively identified, using a standard definition, between
2009 and 2015 through the Canadian Nosocomial Infection Surveillance Program
(CNISP), a network of 64 acute care hospitals. Patient demographic
characteristics, severity of infection and outcomes were reviewed. Molecular
testing was performed on isolates, and strain types were analyzed against
outcomes and epidemiologic trends. RESULTS: Over a 7-year period, 20 623 adult
patients admitted to hospital with health care-associated C. difficile infection
were reported to CNISP, and microbiological data were available for 2690
patients. From 2009 to 2015, the national rate of health care-associated C.
difficile infection decreased from 5.9 to 4.3 per 10 000 patient-days. NAP1
remained the dominant strain type, but infection with this strain has
significantly decreased over time, followed by an increasing trend of infection
with NAP4 and NAP11 strains. The NAP1 strain was significantly associated with a
higher rate of death attributable to C. difficile infection compared with non
NAP1 strains (odds ratio 1.91, 95% confidence interval [CI] 1.29-2.82). Isolates
were universally susceptible to metronidazole; one was nonsusceptible to
vancomycin. The proportion of NAP1 strains within individual centres predicted
their rates of health care-associated C. difficile infection; for every 10%
increase in the proportion of NAP1 strains, the rate of health care-associated C.
difficile infection increased by 3.3% (95% CI 1.7%-4.9%). INTERPRETATION: Rates
of health care-associated C. difficile infection have decreased across Canada. In
nonepidemic settings, NAP4 has emerged as a common strain type, but NAP1,
although decreasing, continues to be the predominant circulating strain and
remains significantly associated with higher attributable mortality.
PMID- 29941435
TI - In defense of Canada's drug plan managers.
PMID- 29941436
TI - Suggestions for managing in-flight emergencies.
PMID- 29941437
TI - Add naloxone to in-flight medical supplies.
PMID- 29941438
TI - Naloxone is becoming more available in airline medical kits.
PMID- 29941439
TI - Many doctors feel "betrayed" by sale of MD Financial Management.
PMID- 29941440
TI - Residency programs grapple with new Indigenous cultural safety training
requirement.
PMID- 29941441
TI - Dr. Jack Tu, a research superstar ahead of his time (1965-2018).
PMID- 29941443
TI - No use for this foot.
PMID- 29941442
TI - Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational
postexposure prophylaxis.
PMID- 29941444
TI - Brain Circuits Mediating Opposing Effects on Emotion and Pain.
AB - The amygdala is important for processing emotion, including negative emotion such
as anxiety and depression induced by chronic pain. Although remarkable progress
has been achieved in recent years on amygdala regulation of both negative (fear)
and positive (reward) behavioral responses, our current understanding is still
limited regarding how the amygdala processes and integrates these negative and
positive emotion responses within the amygdala circuits. In this study with
optogenetic stimulation of specific brain circuits, we investigated how amygdala
circuits regulate negative and positive emotion behaviors, using pain as an
emotional assay in male rats. We report here that activation of the excitatory
pathway from the parabrachial nucleus (PBN) that relays peripheral pain signals
to the central nucleus of amygdala (CeA) is sufficient to cause behaviors of
negative emotion including anxiety, depression, and aversion in normal rats. In
strong contrast, activation of the excitatory pathway from basolateral amygdala
(BLA) that conveys processed corticolimbic signals to CeA dramatically opposes
these behaviors of negative emotion, reducing anxiety and depression, and induces
behavior of reward. Surprisingly, activating the PBN-CeA pathway to simulate pain
signals does not change pain sensitivity itself, but activating the BLA-CeA
pathway inhibits basal and sensitized pain. These findings demonstrate that the
pain signal conveyed through the PBN-CeA pathway is sufficient to drive negative
emotion and that the corticolimbic signal via the BLA-CeA pathway counteracts the
negative emotion, suggesting a top-down brain mechanism for cognitive control of
negative emotion under stressful environmental conditions such as
pain.SIGNIFICANCE STATEMENT It remains unclear how the amygdala circuits
integrate both negative and positive emotional responses and the brain circuits
that link peripheral pain to negative emotion are largely unknown. Using
optogenetic stimulation, this study shows that the excitatory projection from the
parabrachial nucleus to the central nucleus of amygdala (CeA) is sufficient to
drive behaviors of negative emotion including anxiety, depression, and aversion
in rats. Conversely, activation of the excitatory projection from basolateral
amygdala to CeA counteracts each of these behaviors of negative emotion. Thus,
this study identifies a brain pathway that mediates pain-driven negative emotion
and a brain pathway that counteracts these emotion behaviors in a top-down
mechanism for brain control of negative emotion.
PMID- 29941445
TI - Complex Control of Striatal Neurotransmission by Nicotinic Acetylcholine
Receptors via Excitatory Inputs onto Medium Spiny Neurons.
AB - The prevalence of nicotine dependence is higher than that for any other substance
abuse disorder; still, the underlying mechanisms are not fully established. To
this end, we studied acute effects by nicotine on neurotransmission in the
dorsolateral striatum, a key brain region with respect to the formation of
habits. Electrophysiological recordings in acutely isolated brain slices from
rodent showed that nicotine (10 nm to 10 MUm) produced an LTD of evoked field
potentials. Current-clamp recordings revealed no significant effect by nicotine
on membrane voltage or action potential frequency, indicating that the effect by
nicotine is primarily synaptic. Nicotine did not modulate sIPSCs, or the
connectivity between fast-spiking interneurons and medium spiny neurons, as
assessed by whole-cell recordings combined with optogenetics. However, the
frequency of sEPSCs was significantly depressed by nicotine. The effect by
nicotine was mimicked by agonists targeting alpha7- or alpha4-containing nAChRs
and blocked in slices pretreated with a mixture of antagonists targeting these
receptor subtypes. Nicotine-induced LTD was furthermore inhibited by dopamine D2
receptor antagonist and occluded by D2 receptor agonist. In addition, modulation
of cholinergic neurotransmission suppressed the responding to nicotine, which
might reflect upon the postulated role for nAChRs as a presynaptic filter to
differentially govern dopamine release depending on neuronal activity. Nicotine
induced suppression of excitatory inputs onto medium spiny neurons may promote
nicotine-induced locomotor stimulation and putatively initiate neuroadaptations
that could contribute to the transition toward compulsive drug
taking.SIGNIFICANCE STATEMENT To decrease smoking, prevalence factors that may
contribute to the development of nicotine addiction need to be identified. The
data presented here show that nicotine suppresses striatal neurotransmission by
selectively reducing the frequency of excitatory inputs to medium spiny neurons
(MSNs) while rendering excitability, inhibitory neurotransmission, and fast
spiking interneuron-MSN connectivity unaltered. In addition, we show that the
effect displayed by nicotine outlasts the presence of the drug, which could be
fundamental for the addictive properties of nicotine. Considering the inhibitory
tone displayed by MSNs on dopaminergic cell bodies and local terminals, nicotine
induced long-lasting depression of striatal output could play a role in
behavioral transformations associated with nicotine use, and putatively elicit
neuroadaptations underlying compulsive drug-seeking habits.
PMID- 29941446
TI - Axonal Ensheathment in the Nervous System of Lamprey: Implications for the
Evolution of Myelinating Glia.
AB - In the nervous system, myelination of axons enables rapid impulse conduction and
is a specialized function of glial cells. Myelinating glia are the last cell type
to emerge in the evolution of vertebrate nervous systems, presumably in ancient
jawed vertebrates (gnathostomata) because jawless vertebrates (agnathans) lack
myelin. We have hypothesized that, in these unmyelinated species, evolutionary
progenitors of myelinating cells must have existed that should still be present
in contemporary agnathan species. Here, we used advanced electron microscopic
techniques to reveal axon-glia interactions in the sea lamprey Petromyzon marinus
By quantitative assessment of the spinal cord and the peripheral lateral line
nerve, we observed a marked maturation-dependent growth of axonal calibers. In
peripheral nerves, all axons are ensheathed by glial cells either in bundles or,
when larger than the threshold caliber of 3 MUm, individually. The ensheathing
glia are covered by a basal lamina and express SoxE-transcription factors,
features of mammalian Remak-type Schwann cells. In larval lamprey, the
ensheathment of peripheral axons leaves gaps that are closed in adults. CNS axons
are also covered to a considerable extent by glial processes, which contain a
high density of intermediate filaments, glycogen particles, large lipid droplets,
and desmosomes, similar to mammalian astrocytes. Indeed, by in situ
hybridization, these glial cells express the astrocyte marker Aldh1l1 Specimens
were of unknown sex. Our observations imply that radial sorting, ensheathment,
and presumably also metabolic support of axons are ancient functions of glial
cells that predate the evolutionary emergence of myelin in jawed
vertebrates.SIGNIFICANCE STATEMENT We used current electron microscopy techniques
to examine axon-glia units in a nonmyelinated vertebrate species, the sea
lamprey. In the PNS, lamprey axons are fully ensheathed either individually or in
bundles by cells ortholog to Schwann cells. In the CNS, axons associate with
astrocyte orthologs, which contain glycogen and lipid droplets. We suggest that
ensheathment, radial sorting, and metabolic support of axons by glial cells
predate the evolutionary emergence of myelin in ancient jawed vertebrates.
PMID- 29941447
TI - Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in
an East Asian Population.
AB - We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and
its related clinical phenotypes in an East Asian population. We performed whole
exome sequencing in 917 T2D case and control subjects, and the findings were
validated by exome array genotyping in 3,026 participants. In silico replication
was conducted for seven nonsynonymous variants in an additional 13,122
participants. Single-variant and gene-based association tests for T2D were
analyzed. A total of 728,838 variants were identified by whole-exome sequencing.
Among nonsynonymous variants, PAX4 Arg192His increased risk of T2D and GLP1R
Arg131Gln decreased risk of T2D in genome-wide significance (odds ratio [OR]
1.48, P = 4.47 * 10-16 and OR 0.84, P = 3.55 * 10-8, respectively). Another
variant at PAX4 192 codon Arg192Ser was nominally associated with T2D (OR 1.62, P
= 5.18 * 10-4). In T2D patients, PAX4 Arg192His was associated with earlier age
at diagnosis, and GLP1R Arg131Gln was associated with decreased risk of
cardiovascular disease. In control subjects without diabetes, the PAX4 Arg192His
was associated with higher fasting glucose and GLP1R Arg131Gln was associated
with lower fasting glucose and HbA1c level. Gene-based analysis revealed that
SLC30A8 was most significantly associated with decreased risk of T2D (P = 1.0 *
10-4). In summary, we have identified nonsynonymous variants associated with risk
of T2D and related phenotypes in Koreans.
PMID- 29941449
TI - Professional fees calculator to be produced by BMA.
PMID- 29941448
TI - Vascular and Neural Complications in Type 2 Diabetic Rats: Improvement by
Sacubitril/Valsartan Greater Than Valsartan Alone.
AB - Previously, we had shown that a vasopeptidase inhibitor drug containing ACE and
neprilysin inhibitors was an effective treatment for diabetic vascular and neural
complications. However, side effects prevented further development. This led to
the development of sacubitril/valsartan, a drug containing angiotensin II
receptor blocker and neprilysin inhibitor that we hypothesized would be an
effective treatment for diabetic peripheral neuropathy. Using early and late
intervention protocols (4 and 12 weeks posthyperglycemia, respectively), type 2
diabetic rats were treated with valsartan or sacubitril/valsartan for 12 weeks
followed by an extensive evaluation of vascular and neural end points. The
results demonstrated efficacy of sacubitril/valsartan in improving vascular and
neural function was superior to valsartan alone. In the early intervention
protocol, sacubitril/valsartan treatment was found to slow progression of these
deficits and, with late intervention treatment, was found to stimulate
restoration of vascular reactivity, motor and sensory nerve conduction
velocities, and sensitivity/regeneration of sensory nerves of the skin and cornea
in a rat model of type 2 diabetes. These preclinical studies suggest that
sacubitril/valsartan may be an effective treatment for diabetic peripheral
neuropathy, but additional studies will be needed to investigate these effects
further.
PMID- 29941450
TI - Unconventional protein secretion - new insights into the pathogenesis and
therapeutic targets of human diseases.
AB - Most secretory proteins travel through a well-documented conventional secretion
pathway involving the endoplasmic reticulum (ER) and the Golgi complex. However,
recently, it has been shown that a significant number of proteins reach the
plasma membrane or extracellular space via unconventional routes. Unconventional
protein secretion (UPS) can be divided into two types: (i) the extracellular
secretion of cytosolic proteins that do not bear a signal peptide (i.e.
leaderless proteins) and (ii) the cell-surface trafficking of signal-peptide
containing transmembrane proteins via a route that bypasses the Golgi.
Understanding the UPS pathways is not only important for elucidating the
mechanisms of intracellular trafficking pathways but also has important
ramifications for human health, because many of the proteins that are
unconventionally secreted by mammalian cells and microorganisms are associated
with human diseases, ranging from common inflammatory diseases to the lethal
genetic disease of cystic fibrosis. Therefore, it is timely and appropriate to
summarize and analyze the mechanisms of UPS involvement in disease pathogenesis,
as they may be of use for the development of new therapeutic approaches. In this
Review, we discuss the intracellular trafficking pathways of UPS cargos,
particularly those related to human diseases. We also outline the disease
mechanisms and the therapeutic potentials of new strategies for treating UPS
associated diseases.
PMID- 29941451
TI - Meeting report - INDEPTH kick-off meeting.
AB - The precise location of chromatin domains within the cell nucleus has seen
growing recognition in the past decade as an additional mechanism of controlling
gene expression in both plants and animals (Dekker et al., 2017). Consequently,
international efforts are devoted to understanding the organising principle of
this organelle in plants, and notably the nature and the role of functional
compartments on gene expression (Graumann et al., 2013; Sotelo-Silveira et al.,
2018). The European cooperation 'Impact of Nuclear Domains on Gene Expression and
Plant Traits' (INDEPTH) brings together molecular cell biologists, plant
physiologists, bioinformaticians, image analysts and computer scientists. They
aim to address the question of how nuclear architecture, chromatin organisation
and gene expression are connected in plants, particularly in relation to traits
of interest such as biomass, reproduction and resistance to pathogens
(https://www.brookes.ac.uk/indepth/). The kick-off meeting of the INDEPTH
consortium took place in Clermont-Ferrand, France, on 12-14th March 2018, where
more than 80 researchers set the agenda for the coming four years of research and
collaboration.
PMID- 29941452
TI - No off-target mutations in functional genome regions of a CRISPR/Cas9-generated
monkey model of muscular dystrophy.
AB - CRISPR/Cas9 is now widely used in biomedical research and has great potential for
clinical applications. However, the safety and efficacy of this gene-editing
technique are significant issues. Recent reports on mouse models and human cells
have raised concerns that off-target mutations could hamper applying the CRISPR
technology in patients. The high similarities of nonhuman primates to humans in
genome content and organization, genetic diversity, physiology, and cognitive
abilities have made these animals ideal experimental models for understanding
human diseases and developing therapeutics. Off-target mutations of CRISPR/Cas9
have been analyzed in previous studies of nonhuman primates, but no report has
investigated genome-wide off-target effects in living monkeys. Here, we used
rhesus monkeys in which a genetic disorder mimicking Duchenne muscular dystrophy
had previously been produced with CRISPR/Cas9. Using whole-genome sequencing to
comprehensively assess on- and off-target mutations in these animals, we found
that CRISPR/Cas9-based gene editing is active on the expected genomic sites
without producing off-target modifications in other functional regions of the
genome. These findings suggest that the CRISPR/Cas9 technique could be relatively
safe and effective in modeling genetic disease in nonhuman primates and in future
therapeutic research of human diseases.
PMID- 29941453
TI - Periostin promotes liver fibrogenesis by activating lysyl oxidase in hepatic
stellate cells.
AB - Liver fibrosis arises from dysregulated wound healing due to persistent
inflammatory hepatic injury. Periostin is a nonstructural extracellular matrix
protein that promotes organ fibrosis in adults. Here, we sought to identify the
molecular mechanisms in periostin-mediated hepatic fibrosis. Hepatic fibrosis in
periostin-/- mice was attenuated as evidenced by significantly reduced collagen
fibril density and liver stiffness compared with those in WT controls. A single
dose of carbon tetrachloride caused similar acute liver injury in periostin-/-
and WT littermates, and we did not detect significant differences in
transaminases and major fibrosis-related hepatic gene expression between these
two genotypes. Activated hepatic stellate cells (HSCs) are the major periostin
producing liver cell type. We found that in primary rat HSCs in vitro, periostin
significantly increases the expression levels and activities of lysyl oxidase
(LOX) and lysyl oxidase-like (LOXL) isoforms 1-3. Periostin also induced
expression of intra- and extracellular collagen type 1 and fibronectin in HSCs.
Interestingly, periostin stimulated phosphorylation of SMAD2/3, which was
sustained despite short hairpin RNA-mediated knockdown of transforming growth
factor beta (TGFbeta) receptor I and II, indicating that periostin-mediated
SMAD2/3 phosphorylation is independent of TGFbeta receptors. Moreover, periostin
induced the phosphorylation of focal adhesion kinase (FAK) and AKT in HSCs.
Notably, siRNA-mediated FAK knockdown failed to block periostin-induced SMAD2/3
phosphorylation. These results suggest that periostin promotes enhanced matrix
stiffness in chronic liver disease by activating LOX and LOXL, independently of
TGFbeta receptors. Hence, targeting periostin may be of therapeutic benefit in
combating hepatic fibrosis.
PMID- 29941454
TI - Peptide-based sequestration of the adaptor protein Nck1 in pancreatic beta cells
enhances insulin biogenesis and protects against diabetogenic stresses.
AB - One feature of diabetes is the failure of pancreatic beta cells to produce
insulin, but the molecular mechanisms leading to this failure remain unclear.
Increasing evidence supports a role for protein kinase R-like endoplasmic
reticulum kinase (PERK) in the development and function of healthy pancreatic
beta cells. Previously, our group identified the adaptor protein Nck1 as a
negative regulator of PERK. Indeed, we demonstrated that Nck1, by directly
binding PERK autophosphorylated on Tyr561, limits PERK activation and signaling.
Accordingly, we found that stable depletion of Nck1 in beta cells promotes PERK
activation and signaling, increases insulin biosynthesis, and improves cell
viability in response to diabetes-related stresses. Herein, we explored the
therapeutic potential of abrogating the interaction between Nck and PERK to
improve beta-cell function and survival. To do so, we designed and used a peptide
containing the minimal PERK sequence involved in binding Nck1 conjugated to the
cell-permeable protein transduction domain from the HIV protein TAT. In the
current study, we confirm that the synthetic TAT-Tyr(P)561 phosphopeptide
specifically binds the SH2 domain of Nck and prevents Nck interaction with PERK,
thereby promoting basal PERK activation. Moreover, we report that treatment of
beta cells with TAT-Tyr(P)561 inhibits glucolipotoxicity-induced apoptosis,
whereas it enhances insulin production and secretion. Taken together, our results
support the potential of sequestering Nck using a synthetic peptide to enhance
basal PERK activation and create more robust beta cells.
PMID- 29941455
TI - Multiple regions in the extracellular domain of the glycine receptor determine
receptor activity.
AB - Glycine receptors (GlyRs) are Cys-loop receptors that mediate fast synaptic
inhibition in the brain stem and spinal cord. They are involved in the generation
of motor rhythm, reflex circuit coordination, and sensory signal processing and
therefore represent targets for therapeutic interventions. The extracellular
domains (ECDs) of Cys-loop receptors typically contain many aromatic amino acids,
but only those in the receptor binding pocket have been extensively studied.
Here, we show that many Phe residues in the ECD that are not located in the
binding pocket are also involved in GlyR function. We examined these Phe residues
by creating several GlyR variants, characterizing these variants with the two
electrode voltage clamp technique in Xenopus oocytes, and interpreting changes in
receptor parameters by using currently available structural information on the
open and closed states of the GlyR. Substitution of six of the eight Phe residues
in the ECD with Ala resulted in loss of function or significantly increased the
EC50 and also altered the maximal response to the partial GlyR agonist taurine
compared with glycine in those receptor variants that were functional.
Substitutions with other amino acids, combined with examination of nearby
residues that could potentially interact with these Phe residues, suggested
interactions that could be important for GlyR function, and possibly similar
interactions could contribute to the function of other members of the Cys-loop
receptor family. Overall, our results suggest that many ECD regions are important
for GlyR function and that these regions could inform the design of therapeutic
agents targeting GlyR activity.
PMID- 29941456
TI - Mechanism of premature translation termination on a sense codon.
AB - Accurate translation termination by release factors (RFs) is critical for the
integrity of cellular proteomes. Premature termination on sense codons, for
example, results in truncated proteins, whose accumulation could be detrimental
to the cell. Nevertheless, some sense codons are prone to triggering premature
termination, but the structural basis for this is unclear. To investigate
premature termination, we determined a cryo-EM structure of the Escherichia coli
70S ribosome bound with RF1 in response to a UAU (Tyr) sense codon. The structure
reveals that RF1 recognizes a UAU codon similarly to a UAG stop codon, suggesting
that sense codons induce premature termination because they structurally mimic a
stop codon. Hydrophobic interaction between the nucleobase of U3 (the third
position of the UAU codon) and conserved Ile-196 in RF1 is important for
misreading the UAU codon. Analyses of RNA binding in ribonucleoprotein complexes
or by amino acids reveal that Ile-U packing is a frequent protein-RNA-binding
motif with key functional implications. We discuss parallels with eukaryotic
translation termination by the release factor eRF1.
PMID- 29941457
TI - Platelet MEKK3 regulates arterial thrombosis and myocardial infarct expansion in
mice.
AB - MAPKs play important roles in platelet activation. However, the molecular
mechanisms by which MAPKs are regulated in platelets remain largely unknown. Real
time polymerase chain reaction and western blot data showed that MEKK3, a key
MAP3K family member, was expressed in human and mouse platelets. Then,
megakaryocyte/platelet-specific MEKK3-deletion (MEKK3-/- ) mice were developed to
elucidate the platelet-related function(s) of MEKK3. We found that agonist
induced aggregation and degranulation were reduced in MEKK3-/- platelets in
vitro. MEKK3 deficiency significantly impaired integrin alphaIIbbeta3-mediated
inside-out signaling but did not affect the outside-in signaling. At the
molecular level, MEKK3 deficiency led to severely impaired activation of
extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun NH2-terminal kinase
2 but not p38 or ERK5. In vivo, MEKK3-/- mice showed delayed thrombus formation
following FeCl3-induced carotid artery injury. Interestingly, the tail bleeding
time was normal in MEKK3-/- mice. Moreover, MEKK3-/- mice had fewer microthrombi,
reduced myocardial infarction (MI) size, and improved post-MI heart function in a
mouse model of MI. These results suggest that MEKK3 plays important roles in
platelet MAPK activation and may be used as a new effective target for
antithrombosis and prevention of MI expansion.
PMID- 29941458
TI - Refining risk classification in childhood B acute lymphoblastic leukemia: results
of DFCI ALL Consortium Protocol 05-001.
AB - Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05-001 tested a new
risk stratification system in children and adolescents with newly diagnosed acute
lymphoblastic leukemia (ALL). At study entry, B-ALL patients were classified as
standard risk (SR) or high risk (HR) based on age, white blood cell (WBC) count,
and central nervous system status. After achieving complete remission (CR),
patients with high end-induction minimal residual disease (MRD) (>=10-3 by
polymerase chain reaction analysis of patient-specific antigen receptor
rearrangements) and/or adverse cytogenetics (KMT2A rearrangement or hypodiploidy)
were reclassified as very high risk (VHR) and received intensified therapy. IKZF1
deletion status was retrospectively evaluated by multiplex ligation-dependent
probe amplification. Between 2005 and 2011, 678 Philadelphia chromosome-negative
B-ALL patients aged 1 to 18 years enrolled; 651 achieved CR and 648 received a
final risk group. Among all 678 patients, 5-year event-free survival (EFS) was
87% (95% confidence interval [CI], 84-89) and overall survival 93% (95% CI, 90
94). Five-year disease-free survival of SR patients (N = 407) was 94% (95% CI, 91
96), HR (N = 176) was 84% (95% CI, 77-88), and VHR (N = 65) was 79% (95% CI, 67
87). IKZF1 deletion was present in 62 of 385 (16%) assessed patients and was
associated with inferior 5-year EFS (63%; 95% CI, 49%-74% vs 88%; 95% CI, 84%
91%; P < .001), and higher 5-year cumulative incidence of relapse, including
among those with low MRD (24% vs 8%, P = .001). In multivariable analysis, age
>=15 years, WBC >=50 * 109/L, IKZF1 deletion, and MRD >=10-4 was each associated
with inferior outcome. In conclusion, risk-stratified therapy on DFCI 05-001
resulted in favorable outcomes for B-ALL patients, including those with VHR
features. IKZF1 deletion was an independent predictor of inferior outcome. This
trial was registered at www.clinicaltrials.gov as #NCT00400946.
PMID- 29941460
TI - Medecins Sans Frontieres is focus of sex scandal in charity sector.
PMID- 29941459
TI - 161533 TriKE stimulates NK-cell function to overcome myeloid-derived suppressor
cells in MDS.
AB - Myelodysplastic syndrome (MDS) is a clonal heterogeneous stem cell disorder
driven by multiple genetic and epigenetic alterations resulting in ineffective
hematopoiesis. MDS has a high frequency of immune suppressors, including myeloid
derived suppressor cells (MDSCs), that collectively result in a poor immune
response. MDSCs in MDS patients express CD155 that ligates the T-cell
immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and delivers an
inhibitory signal to natural killer (NK) cells. To mediate a productive immune
response against MDS, negative regulatory checkpoints, like TIGIT, expressed on
MDS NK cells must be overcome. NK cells can be directed to lyse MDS cells by
bispecific killer engagers (BiKEs) that ligate CD16 on NK cells and CD33 on MDS
cells. However, such CD16 * CD33 (1633) BiKEs do not induce the proliferative
response in MDS NK cells needed to sustain their function. Here, we show that the
addition of an NK stimulatory cytokine, interleukin-15 (IL-15), into the BiKE
platform leads to productive IL-15 signaling without TIGIT upregulation on NK
cells from MDS patients. Lower TIGIT expression allowed NK cells to resist MDSC
inhibition. When compared with 1633 BiKE, 161533 trispecific killer engager
(TriKE)-treated NK cells demonstrated superior killing kinetics associated with
increased STAT5 phosphorylation. Furthermore, 161533 TriKE-treated MDS NK cells
had higher proliferation and enhanced NK-cell function than 1633 BiKE-treated
cells without the IL-15 linker. Collectively, our data demonstrate novel
characteristics of the 161533 TriKE that support its application as an
immunotherapeutic agent for MDS patients.
PMID- 29941461
TI - Trace Amines and Their Receptors.
AB - Trace amines are endogenous compounds classically regarded as comprising beta
phenylethyalmine, p-tyramine, tryptamine, p-octopamine, and some of their
metabolites. They are also abundant in common foodstuffs and can be produced and
degraded by the constitutive microbiota. The ability to use trace amines has
arisen at least twice during evolution, with distinct receptor families present
in invertebrates and vertebrates. The term "trace amine" was coined to reflect
the low tissue levels in mammals; however, invertebrates have relatively high
levels where they function like mammalian adrenergic systems, involved in "fight
or-flight" responses. Vertebrates express a family of receptors termed trace
amine-associated receptors (TAARs). Humans possess six functional isoforms
(TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9), whereas some fish species express
over 100. With the exception of TAAR1, TAARs are expressed in olfactory
epithelium neurons, where they detect diverse ethological signals including
predators, spoiled food, migratory cues, and pheromones. Outside the olfactory
system, TAAR1 is the most thoroughly studied and has both central and peripheral
roles. In the brain, TAAR1 acts as a rheostat of dopaminergic, glutamatergic, and
serotonergic neurotransmission and has been identified as a novel therapeutic
target for schizophrenia, depression, and addiction. In the periphery, TAAR1
regulates nutrient-induced hormone secretion, suggesting its potential as a novel
therapeutic target for diabetes and obesity. TAAR1 may also regulate immune
responses by regulating leukocyte differentiation and activation. This article
provides a comprehensive review of the current state of knowledge of the
evolution, physiologic functions, pharmacology, molecular mechanisms, and
therapeutic potential of trace amines and their receptors in vertebrates and
invertebrates.
PMID- 29941462
TI - High Mobility Group Protein 1 Reverses Immune System Paralysis in Late-Phase
Sepsis.
AB - High mobility group protein 1 (HMGB1) is considered to be the primary
inflammatory factor triggering immune paralysis in late-phase sepsis. In this
study, however, we wanted to explore the possibility of using HMGB1 to boost
local differentiation of bone marrow cells (BMCs) into regulatory dendritic cells
(DCs) in vivo, thereby inducing immune reversal in late-phase sepsis and
improving the prognosis. For this purpose, sepsis was induced by cecal ligation
and puncture (CLP). Mice were injected intraperitoneally with HMGB1 (10, 50, or
250 MUg/kg of body weight) 7 days before CLP. BMCs and liver immune cells were
isolated at 0, 3, 5, and 7 days post-CLP. Mice were intranasally infected with
Pseudomonas aeruginosa 3 days post-CLP as a secondary pneumonia infection model.
BMCs and liver cells isolated from septic mice pretreated with HMGB1 were
adoptively transferred into CLP mice. GFP+-C57BL/6 and C3H/HeN-C3H/HeJ parabiosis
models were established. We found that HMGB1 pretreatment improved the survival
of sepsis and increased the numbers of BMCs and liver immune cells in CLP mice.
Furthermore, HMGB1 stimulation improved survival in the secondary pneumonia
infection model. HMGB1 increased the number as well as the percentage of CD11c-
CD45RBhigh DCs in septic BM and liver. Adoptive transfer of septic cells
pretreated with HMGB1 into CLP mice attenuated sepsis. HMGB1 enhanced the
redistribution of CD11c- CD45RBhigh DCs through TLR4 signaling in parabiosis
models. We conclude that HMGB1 triggers immune reversal through the mobilization,
redistribution, and local immune differentiation of BMCs, thereby compensating
for impaired immunity and leading to sufficient bacterial eradication.
PMID- 29941464
TI - Programming of the reproductive axis by hormonal and genetic manipulation in
mice.
AB - In mammals, the reproductive function is controlled by the hypothalamic-pituitary
gonadal axis. During development, mechanisms mediated by gonadal steroids exert
an imprinting at the hypothalamic-pituitary level, by establishing sexual
differences in the circuits that control male and female reproduction. In
rodents, the testicular production of androgens increases drastically during the
fetal/neonatal stage. This process is essential for the masculinization of the
reproductive tract, genitals and brain. The conversion of androgens to estrogens
in the brain is crucial for the male sexual differentiation and behavior.
Conversely, feminization of the brain occurs in the absence of high levels of
gonadal steroids during the perinatal period in females. Potential genetic
contribution to the differentiation of brain cells through direct effects of
genes located on sex chromosomes is also relevant. In this review, we will focus
on the phenotypic alterations that occur on the hypothalamic-pituitary-gonadal
axis of transgenic mice with persistently elevated expression of the human
chorionic gonadotropin hormone (hCG). Excess of endogenously synthesized gonadal
steroids due to a constant hCG stimulation is able to disrupt the developmental
programming of the hypothalamic-pituitary axis in both transgenic males and
females. Locally produced estrogens by the hypothalamic aromatase might play a
key role in the phenotype of these mice. The "four core genotypes" mouse model
demonstrated a potential influence of sex chromosome genes in brain
masculinization before critical periods of sex differentiation. Thus, hormonal
and genetic factors interact to regulate the local production of the
neurosteroids necessary for the programming of the male and female reproductive
function.
PMID- 29941463
TI - Caspases-1 and caspase-11 mediate pyroptosis, inflammation, and control of
Brucella joint infection.
AB - Brucellosis, caused by the intracellular bacterial pathogen Brucella, is a
zoonotic disease for which arthritis is the most common focal complication in
humans. Here we investigated the role of inflammasomes and their effectors,
including IL-1, IL-18 and pyroptosis, on inflammation and control of infection
during Brucella-induced arthritis. Early in infection, both caspase-1 and caspase
11 were found to initiate joint inflammation and pro-inflammatory cytokine
production. However, by one week post-infection caspase-1 and caspase-11 also
contributed to control of Brucella joint infection. Inflammasome dependent
restriction of Brucella joint burdens did not require AIM2 or NLRP3. IL-1R had a
modest effect on Brucella-induced joint swelling, but mice lacking IL-1R were not
impaired in their ability to control infection of the joint by Brucella In
contrast, IL-18 contributed to the initiation of joint swelling and control of
joint Brucella infection. Caspase1/11-dependent cell death was observed in vivo,
and in vitro studies demonstrated caspase-1 and caspase-11 both induce pyroptosis
which limited Brucella infection in macrophages. Brucella LPS alone was also able
to induce caspase-11 dependent pyroptosis. Collectively these data demonstrate
inflammasomes induce inflammation in an IL-18 dependent manner, and inflammasome
dependent IL-18 and pyroptosis restrict Brucella infection.
PMID- 29941465
TI - NHS is ignoring smoking at great cost, says Royal College of Physicians.
PMID- 29941466
TI - High-Sensitivity Cardiac Troponin-Based Strategies for the Assessment of Chest
Pain Patients-A Review of Validation and Clinical Implementation Studies.
AB - BACKGROUND: The introduction of high-sensitivity cardiac troponin (hs-cTn) assays
has improved the early assessment of chest pain patients. A number of hs-cTn
based algorithms and accelerated diagnostic protocols (ADPs) have been developed
and tested subsequently. In this review, we summarize the data on the performance
and clinical utility of these strategies. CONTENT: We reviewed studies
investigating the diagnostic and prognostic performance of hs-cTn algorithms
[level of detection (LoD) strategy, 0/1-h, 0/2-h, and 0/3-h algorithms) and of hs
cTn-based ADPs, together with the implications of these strategies when
implemented as clinical routine. The LoD strategy, when combined with a
nonischemic electrocardiogram, is best suited for safe rule-out of myocardial
infarction and the identification of patients eligible for early discharge from
the emergency department. The 0/1-h algorithms appear to identify most patients
as being eligible for rule-out. The hs-cTn-based ADPs mainly focus on prognostic
assessment, which is in contrast with the hs-cTn algorithms. They identify
smaller proportions of rule-out patients, but there is increasing evidence from
prospective studies on their successful clinical implementation. Such information
is currently lacking for hs-cTn algorithms. CONCLUSIONS: There is a trade-off
between safety and efficacy for different hs-cTn-based strategies. This trade-off
should be considered for the intended strategy, along with its user-friendliness
and evidence from clinical implementation studies. However, several gaps in
knowledge remain. At present, we suggest the use of an ADP in conjunction with
serial hs-cTn results to optimize the early assessment of chest pain patients.
PMID- 29941467
TI - Pharmacogenetics of Warfarin Therapy.
PMID- 29941468
TI - Genome-Wide Analysis of Circulating Cell-Free DNA Copy Number Detects Active
Melanoma and Predicts Survival.
AB - BACKGROUND: A substantial number of melanoma patients develop local or metastatic
recurrence, and early detection of these is vital to maximise benefit from new
therapies such as inhibitors of BRAF and MEK, or immune checkpoints. This study
explored the use of novel DNA copy-number profiles in circulating cell-free DNA
(cfDNA) as a potential biomarker of active disease and survival. PATIENTS AND
METHODS: Melanoma patients were recruited from oncology and dermatology clinics
in Sheffield, UK, and cfDNA was isolated from stored blood plasma. Using low
coverage whole-genome sequencing, we created copy-number profiles from cfDNA from
83 melanoma patients, 44 of whom had active disease. We used scoring algorithms
to summarize copy-number aberrations and investigated their utility in
multivariable logistic and Cox regression analyses. RESULTS: The copy-number
aberration score (CNAS) was a good discriminator of active disease (odds ratio,
3.1; 95% CI, 1.5-6.2; P = 0.002), and CNAS above or below the 75th percentile
remained a significant discriminator in multivariable analysis for active disease
(P = 0.019, with area under ROC curve of 0.90). Additionally, mortality was
higher in those with CNASs above the 75th percentile than in those with lower
scores (HR, 3.4; 95% CI, 1.5-7.9; P = 0.005), adjusting for stage of disease,
disease status (active or resected), BRAF status, and cfDNA concentration.
CONCLUSIONS: This study demonstrates the potential of a de novo approach
utilizing copy-number profiling of cfDNA as a biomarker of active disease and
survival in melanoma. Longitudinal analysis of copy-number profiles as an early
marker of relapsed disease is warranted.
PMID- 29941470
TI - Enhanced Liver Fibrosis Score as a Predictor of Hepatocellular Carcinoma.
PMID- 29941469
TI - Clinical Validation of a Novel High-Sensitivity Cardiac Troponin I Assay for
Early Diagnosis of Acute Myocardial Infarction.
AB - BACKGROUND: Clinical performance of the novel high-sensitivity cardiac troponin I
(Siemens-hs-cTnI-Centaur) assay is unknown. We aimed to clinically validate the
Siemens-hs-cTnI-Centaur assay and develop 0/1-h and 0/2-h algorithms. METHODS: We
enrolled patients presenting to the emergency department with symptoms suggestive
of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated
by 2 independent cardiologists including all clinical information twice: first,
using serial hs-cTnT (Roche-Elecsys, primary analysis); second, using hs-cTnI
(Abbott-Architect, secondary analysis) measurements in addition to the clinically
applied (hs)-cTn. Siemens-hs-cTnI-Centaur was measured at presentation, 1 h, and
2 h. The primary objective was a direct comparison of diagnostic accuracy,
quantified by the area under the ROC curve (AUC), of Siemens-hs-cTnI-Centaur vs
the 2 established hs-cTn assays (Roche-hs-cTnT-Elecsys, Abbott-hs-cTnI
Architect). Secondary objectives included the development of Siemens-hs-cTnI
Centaur-specific 0/1-h and 0/2-h algorithms. RESULTS: AMI was the final diagnosis
in 318 of 1755 (18%) patients (using Roche-hs-cTnT-Elecsys for adjudication). The
AUC at presentation for Siemens-hs-cTnI-Centaur was 0.94 (95% CI, 0.92-0.96) and
comparable with 0.95 (95% CI, 0.93-0.97) for Roche-hs-cTnT-Elecsys and 0.93 (95%
CI, 0.90-0.96) for Abbott-hs-cTnI-Architect. Applying the derived Siemens-hs-cTnI
Centaur 0/1-h algorithm to the validation cohort, 46% of patients were ruled out
(sensitivity, 99.1%; 95% CI, 95.3-100), and 18% of patients were ruled in
(specificity, 94.1%; 95% CI, 91.8-95.9). The Siemens-hs-cTnI-Centaur 0/2-h
algorithm ruled out 55% of patients (sensitivity, 100%; 95% CI, 94.1-100), and
ruled in 18% of patients (specificity, 96.0%; 95% CI, 93.1-97.9). Findings were
confirmed in the secondary analyses using serial measurements of Abbott-hs-cTnI
Architect for adjudication. CONCLUSIONS: Diagnostic accuracy and clinical utility
of the novel Siemens-hs-cTnI-Centaur assay are high and comparable with the
established hs-cTn assays. ClinicalTrials.gov Identifier: NCT00470587.
PMID- 29941471
TI - The Inadvertent Discovery of Human Fetal Cell Microchimerism.
PMID- 29941472
TI - The EuBIVAS: Within- and Between-Subject Biological Variation Data for
Electrolytes, Lipids, Urea, Uric Acid, Total Protein, Total Bilirubin, Direct
Bilirubin, and Glucose.
AB - BACKGROUND: The European Federation of Clinical Chemistry and Laboratory Medicine
European Biological Variation Study (EuBIVAS) has been established to deliver
rigorously determined data describing biological variation (BV) of clinically
important measurands. Here, EuBIVAS-based BV estimates of serum electrolytes,
lipids, urea, uric acid, total protein, total bilirubin, direct bilirubin, and
glucose, as well as their associated analytical performance specifications
(APSs), are presented. METHOD: Samples were drawn from 91 healthy individuals (38
male, 53 female; age range, 21-69 years) for 10 consecutive weeks at 6 European
laboratories. Samples were stored at -80 degrees C before duplicate analysis of
all samples on an ADVIA 2400 (Siemens Healthineers). Outlier and homogeneity
analyses were performed, followed by CV-ANOVA on trend-corrected data, when
relevant, to determine BV estimates with CIs. RESULTS: The within-subject BV
(CVI) estimates of all measurands, except for urea and LDL cholesterol, were
lower than estimates available in an online BV database, with differences being
most pronounced for HDL cholesterol, glucose, and direct bilirubin. Significant
differences in CVI for men and women/women <50 years of age were evident for uric
acid, triglycerides, and urea. The CVA obtained for sodium and magnesium exceeded
the EuBIVAS-based APS for imprecision. CONCLUSIONS: The EuBIVAS, which is fully
compliant with the recently published Biological Variation Data Critical
Appraisal Checklist, has produced well-characterized, high-quality BV estimates
utilizing a stringent experimental protocol. These new reference data deliver
revised and more exacting APS and reference change values for commonly used
clinically important measurands, thus having direct relevance to diagnostics
manufacturers, service providers, clinical users, and ultimately patients.
PMID- 29941473
TI - Drosophila immune cells extravasate from vessels to wounds using Tre1 GPCR and
Rho signaling.
AB - Inflammation is pivotal to fight infection, clear debris, and orchestrate repair
of injured tissues. Although Drosophila melanogaster have proven invaluable for
studying extravascular recruitment of innate immune cells (hemocytes) to wounds,
they have been somewhat neglected as viable models to investigate a key rate
limiting component of inflammation-that of immune cell extravasation across
vessel walls-due to their open circulation. We have now identified a period
during pupal development when wing hearts pulse hemolymph, including circulating
hemocytes, through developing wing veins. Wounding near these vessels triggers
local immune cell extravasation, enabling live imaging and correlative light
electron microscopy of these events in vivo. We show that RNAi knockdown of
immune cell integrin blocks diapedesis, just as in vertebrates, and we uncover a
novel role for Rho-like signaling through the GPCR Tre1, a gene previously
implicated in the trans-epithelial migration of germ cells. We believe this new
Drosophila model complements current murine models and provides new mechanistic
insight into immune cell extravasation.
PMID- 29941474
TI - A timer for analyzing temporally dynamic changes in transcription during
differentiation in vivo.
AB - Understanding the mechanisms of cellular differentiation is challenging because
differentiation is initiated by signaling pathways that drive temporally dynamic
processes, which are difficult to analyze in vivo. We establish a new tool, Timer
of cell kinetics and activity (Tocky; or toki [time in Japanese]). Tocky uses the
fluorescent Timer protein, which spontaneously shifts its emission spectrum from
blue to red, in combination with computer algorithms to reveal the dynamics of
differentiation in vivo. Using a transcriptional target of T cell receptor (TCR)
signaling, we establish Nr4a3-Tocky to follow downstream effects of TCR
signaling. Nr4a3-Tocky reveals the temporal sequence of events during regulatory
T cell (Treg) differentiation and shows that persistent TCR signals occur during
Treg generation. Remarkably, antigen-specific T cells at the site of autoimmune
inflammation also show persistent TCR signaling. In addition, by generating Foxp3
Tocky, we reveal the in vivo dynamics of demethylation of the Foxp3 gene. Thus,
Tocky is a tool for cell biologists to address previously inaccessible questions
by directly revealing dynamic processes in vivo.
PMID- 29941475
TI - The molecular recognition of phosphatidic acid by an amphipathic helix in Opi1.
AB - A key event in cellular physiology is the decision between membrane biogenesis
and fat storage. Phosphatidic acid (PA) is an important intermediate at the
branch point of these pathways and is continuously monitored by the
transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we
report on the mechanism of membrane recognition by Opi1 and identify an
amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS).
The insertion of the AH into the membrane core renders Opi1 sensitive to the
lipid acyl chain composition and provides a means to adjust membrane biogenesis.
By rational design of the AH, we tune the membrane-binding properties of Opi1 and
control its responsiveness in vivo. Using extensive molecular dynamics
simulations, we identify two PA-selective three-finger grips that tightly bind
the PA phosphate headgroup while interacting less intimately with PS. This work
establishes lipid headgroup selectivity as a new feature in the family of AH
containing membrane property sensors.
PMID- 29941477
TI - Hermansky-Pudlak syndrome with a novel genetic variant in HPS1 and subsequent
accelerated pulmonary fibrosis: significance for phenocopy diseases.
AB - The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive
disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA),
bleeding diatheses and, in selected individuals, early-onset accelerated
pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young
man who presented following a self-directed literature review prompted by severe
bleeding complications following minor surgical and dental procedures in the
context of OCA. HPS was clinically suspected, with subsequent genetic testing
confirming biallelic mutations in the HPS1 gene. Of interest, this is the only
described HPS type 1 patient with two different (compound heterozygote) splice
site variants in HPS1 In addition to detailing a novel genetic result and
outlining the progressive clinical course of disease in this case, we discuss the
management of HPS, the prognostic value of subtype analysis and the technical
difficulties relating to transplantation in the case of HPS-associated advanced
pulmonary fibrosis. This case also illustrates the concept of lung phenocopy
relationships and the potential for elucidating the pathogenesis of more common
pulmonary disorders by studying genetic diseases that result in similar
phenotypes. Furthermore, it re-emphasises the importance of the patient voice,
particularly with regard to complex diagnoses and rare diseases.
PMID- 29941476
TI - Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle
centering mechanism.
AB - The plane of cell division is defined by the final position of the mitotic
spindle. The spindle is pulled and rotated to the correct position by cortical
dynein. However, it is unclear how the spindle's rotational center is maintained
and what the consequences of an equatorially off centered spindle are in human
cells. We analyzed spindle movements in 100s of cells exposed to protein
depletions or drug treatments and uncovered a novel role for MARK2 in maintaining
the spindle at the cell's geometric center. Following MARK2 depletion, spindles
glide along the cell cortex, leading to a failure in identifying the correct
division plane. Surprisingly, spindle off centering in MARK2-depleted cells is
not caused by excessive pull by dynein. We show that MARK2 modulates mitotic
microtubule growth and length and that codepleting mitotic centromere-associated
protein (MCAK), a microtubule destabilizer, rescues spindle off centering in
MARK2-depleted cells. Thus, we provide the first insight into a spindle-centering
mechanism needed for proper spindle rotation and, in turn, the correct division
plane in human cells.
PMID- 29941478
TI - Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney
Function.
AB - BACKGROUND: Canagliflozin is approved for glucose lowering in type 2 diabetes and
confers cardiovascular and renal benefits. We sought to assess whether it had
benefits in people with chronic kidney disease, including those with an estimated
glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the
drug is not currently approved for use. METHODS: The CANVAS Program randomized 10
142 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2 to
canagliflozin or placebo. The primary outcome was a composite of cardiovascular
death, nonfatal myocardial infarction, or nonfatal stroke, with other
cardiovascular, renal, and safety outcomes. This secondary analysis describes
outcomes in participants with and without chronic kidney disease, defined as eGFR
<60 and >=60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45,
45 to <60, 60 to <90, and >=90 mL/min/1.73 m2). RESULTS: At baseline, 2039
(20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history
of cardiovascular disease. The effect of canagliflozin on the primary outcome was
similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55
0.90) and those with preserved kidney function (hazard ratio, 0.92; 95% CI, 0.79
1.07; P heterogeneity = 0.08). Relative effects on most cardiovascular and renal
outcomes were similar across eGFR subgroups, with possible heterogeneity
suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity =
0.01), as were results for almost all safety outcomes. CONCLUSIONS: The effects
of canagliflozin on cardiovascular and renal outcomes were not modified by
baseline level of kidney function in people with type 2 diabetes and a history or
high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2.
Reassessing current limitations on the use of canagliflozin in chronic kidney
disease may allow additional individuals to benefit from this therapy. CLINICAL
TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers:
NCT01032629, NCT01989754.
PMID- 29941479
TI - UK medical school places must double, says Royal College of Physicians.
PMID- 29941480
TI - Stroke: Highlights of Selected Articles.
PMID- 29941481
TI - The Combination of the PARP Inhibitor Olaparib and the WEE1 Inhibitor AZD1775 as
a New Therapeutic Option for Small Cell Lung Cancer.
AB - Purpose: Introduced in 1987, platinum-based chemotherapy remains standard of care
for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor.
Prominent barriers to progress are paucity of tumor tissue to identify drug
targets and patient-relevant models to interrogate novel therapies. Following our
development of circulating tumor cell patient-derived explants (CDX) as models
that faithfully mirror patient disease, here we exploit CDX to examine new
therapeutic options for SCLC.Experimental Design: We investigated the efficacy of
the PARP inhibitor olaparib alone or in combination with the WEE1 kinase
inhibitor AZD1775 in 10 phenotypically distinct SCLC CDX in vivo and/or ex vivo
These CDX represent chemosensitive and chemorefractory disease including the
first reported paired CDX generated longitudinally before treatment and upon
disease progression.Results: There was a heterogeneous depth and duration of
response to olaparib/AZD1775 that diminished when tested at disease progression.
However, efficacy of this combination consistently exceeded that of
cisplatin/etoposide, with cures in one CDX model. Genomic and protein analyses
revealed defects in homologous recombination repair genes and oncogenes that
induce replication stress (such as MYC family members), predisposed CDX to
combined olaparib/AZD1775 sensitivity, although universal predictors of response
were not noted.Conclusions: These preclinical data provide a strong rationale to
trial this combination in the clinic informed by prevalent, readily accessed
circulating tumor cell-based biomarkers. New therapies will be evaluated in SCLC
patients after first-line chemotherapy, and our data suggest that the combination
of olaparib/AZD1775 should be used as early as possible and before disease
relapse. Clin Cancer Res; 24(20); 5153-64. (c)2018 AACR.
PMID- 29941482
TI - Two Weeks' Notice from Allogeneic Sources.
AB - A novel pipeline for neoantigen-specific T-cell receptor (TCR) identification has
been validated in ovarian cancer, making use of HLA-matched allogeneic healthy
donor T cells. This workflow allows for the identification of tumor-specific TCRs
2 weeks after antigen-specific stimulation and eliminates problematic patient-to
patient variation in the selection of neoantigen-specific TCRs. Clin Cancer Res;
24(21); 5195-7. (c)2018 AACR See related article by Matsuda et al., p. 5357.
PMID- 29941483
TI - Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine
Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer.
AB - Purpose: Uterine serous carcinoma (USC) is a rare and aggressive variant of
endometrial cancer. Whole-exome sequencing (WES) studies have recently reported c
Myc gene amplification in a large number of USCs, suggesting c-Myc as a potential
therapeutic target. We investigated the activity of novel BET bromodomain
inhibitors (GS-5829 and GS-626510, Gilead Sciences Inc.) and JQ1 against primary
USC cultures and USC xenografts.Experimental Design: We evaluated c-Myc
expression by qRT-PCR in a total of 45 USCs including fresh-frozen tumor tissues
and primary USC cell lines. We also performed IHC and Western blot experiments in
8 USC tumors. USC cultures were evaluated for sensitivity to GS-5829, GS-626510,
and JQ1 in vitro using proliferation, viability, and apoptosis assays. Finally,
the in vivo activity of GS-5829, GS-626510, and JQ1 was studied in USC-ARK1 and
USC-ARK2 mouse xenografts.Results: Fresh-frozen USC and primary USC cell lines
overexpressed c-Myc when compared with normal tissues (P = 0.0009 and 0.0083,
respectively). High c-Myc expression was found in 7 of 8 of primary USC cell
lines tested by qRT-PCR and 5 of 8 tested by IHC. In vitro experiments
demonstrated high sensitivity of USC cell lines to the exposure to GS-5829, GS
626510, and JQ1 with BET inhibitors causing a dose-dependent decrease in the
phosphorylated levels of c-Myc and a dose-dependent increase in caspase
activation (apoptosis). In comparative in vivo experiments, GS-5829 and/or GS
626510 were found more effective than JQ1 at the concentrations/doses used in
decreasing tumor growth in both USC-ARK1 and USC-ARK2 mouse xenograft
models.Conclusions: GS-5829 and GS-626510 may represent novel, highly effective
therapeutics agents against recurrent/chemotherapy-resistant USC-overexpressing c
Myc. Clinical studies with GS-5829 in patients with USC harboring chemotherapy
resistant disease are warranted. Clin Cancer Res; 24(19); 4845-53. (c)2018 AACR.
PMID- 29941484
TI - TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with
IDH Wild-Type Glioblastomas: A Pilot Prospective Study.
AB - Purpose: We conducted a pilot study to assess the feasibility and the potential
implications of detecting TERT promoter (TERTp)-mutant cell-free tumor-derived
DNA (tDNA) in the cerebrospinal fluid (CSF) and plasma of glioblastoma
patients.Experimental Design: Matched CSF and plasma samples were collected in 60
patients with glial tumors. The CSF collection was obtained during surgery,
before any surgical manipulation of the tumor. The extracted tDNA and
corresponding tumor DNA samples were analyzed for TERTp and isocitrate
dehydrogenase (IDH) hotspot mutations. In addition, the variant allele frequency
(VAF) of TERTp mutation in the CSF-tDNA was correlated with tumor features and
patients' outcome.Results: Thirty-eight patients had TERTp-mutant/IDH wild-type
glioblastomas. The matched TERTp mutation in the CSF-tDNA was successfully
detected with 100% specificity (95% CI, 87.6-100%) and 92.1% sensitivity (95% CI,
78.6-98.3%) (n = 35/38). In contrast, the sensitivity in the plasma-tDNA was far
lower [n = 3/38, 7.9% (95% CI, 1.6-21.4%)]. We concordantly observed a longer
overall survival of patients with low VAF in the CSF-tDNA when compared with
patients with high VAF, irrespective of using the lower quartile VAF [11.45%;
14.0 mo. (95% confidence interval, CI, 10.3-17.6) vs. 8.6 mo. (95% CI, 4.1-13.2),
P = 0.035], the lower third VAF [13%; 15.4 mo. (95% CI, 11.6-19.2) vs. 8.3 mo.
(95% CI, 2.3-14.4), P = 0.008], or the median VAF [20.3%; 14.0 mo. (95% CI, 9.2
18.7) vs. 8.6 mo. (95% CI, 7.5-9.8), P = 0.062] to dichotomize the
patients.Conclusions: This pilot study highlights the value of CSF-tDNA for an
accurate and reliable detection of TERTp mutations. Furthermore, our findings
suggest that high TERTp mutation VAF levels in the CSF-tDNA may represent a
suitable predictor of poor survival in glioblastoma patients. Further studies are
needed to complement the findings of our exploratory analysis. Clin Cancer Res;
24(21); 5282-91. (c)2018 AACR.
PMID- 29941485
TI - Loss of E-cadherin Enhances IGF1-IGF1R Pathway Activation and Sensitizes Breast
Cancers to Anti-IGF1R/InsR Inhibitors.
AB - Purpose: Insulin-like growth factor 1 (IGF1) signaling regulates breast cancer
initiation and progression and associated cancer phenotypes. We previously
identified E-cadherin (CDH1) as a repressor of IGF1 signaling and in this study
examined how loss of E-cadherin affects IGF1R signaling and response to anti
IGF1R/insulin receptor (InsR) therapies in breast cancer.Experimental Design:
Breast cancer cell lines were used to assess how altered E-cadherin levels
regulate IGF1R signaling and response to two anti-IGF1R/InsR therapies. In situ
proximity ligation assay (PLA) was used to define interaction between IGF1R and E
cadherin. TCGA RNA-seq and RPPA data were used to compare IGF1R/InsR activation
in estrogen receptor-positive (ER+) invasive lobular carcinoma (ILC) and invasive
ductal carcinoma (IDC) tumors. ER+ ILC cell lines and xenograft tumor explant
cultures were used to evaluate efficacy to IGF1R pathway inhibition in
combination with endocrine therapy.Results: Diminished functional E-cadherin
increased both activation of IGF1R signaling and efficacy to anti-IGF1R/InsR
therapies. PLA demonstrated a direct endogenous interaction between IGF1R and E
cadherin at points of cell-cell contact. Increased expression of IGF1 ligand and
levels of IGF1R/InsR phosphorylation were observed in E-cadherin-deficient ER+
ILC compared with IDC tumors. IGF1R pathway inhibitors were effective in
inhibiting growth in ER+ ILC cell lines and synergized with endocrine therapy and
similarly IGF1R/InsR inhibition reduced proliferation in ILC tumor explant
culture.Conclusions: We provide evidence that loss of E-cadherin hyperactivates
the IGF1R pathway and increases sensitivity to IGF1R/InsR targeted therapy, thus
identifying the IGF1R pathway as a potential novel target in E-cadherin-deficient
breast cancers. Clin Cancer Res; 24(20); 5165-77. (c)2018 AACR.
PMID- 29941486
TI - Phase I and Biomarker Study of Plerixafor and Bevacizumab in Recurrent High-Grade
Glioma.
AB - Purpose: Although antiangiogenic therapy for high-grade glioma (HGG) is
promising, responses are not durable. Correlative clinical studies suggest that
the SDF-1alpha/CXCR4 axis may mediate resistance to VEGFR inhibition. Preclinical
data have demonstrated that plerixafor (a reversible CXCR4 inhibitor) could
inhibit glioma progression after anti-VEGF pathway inhibition. We conducted a
phase I study to determine the safety of plerixafor and bevacizumab in recurrent
HGG.Patients and Methods: Part 1 enrolled 23 patients with a 3 * 3 dose
escalation design to a maximum planned dose of plerixafor 320 MUg/kg
subcutaneously on days 1 to 21 and bevacizumab 10 mg/kg intravenously on days 1
and 15 of each 28-day cycle. Cerebrospinal fluid (CSF) and plasma samples were
obtained for pharmacokinetic analyses. Plasma and cellular biomarkers were
evaluated before and after treatment. Part 2 enrolled 3 patients and was a
surgical study to determine plerixafor's penetration in tumor tissue.Results: In
Part 1, no dose-limiting toxicities were seen at the maximum planned dose of
plerixafor + bevacizumab. Treatment was well tolerated. After plerixafor 320
MUg/kg treatment, the average CSF drug concentration was 26.8 +/- 19.6 ng/mL.
Plerixafor concentration in resected tumor tissue from patients pretreated with
plerixafor was 10 to 12 MUg/g. Circulating biomarker data indicated that
plerixafor + bevacizumab induces rapid and persistent increases in plasma SDF
1alpha and placental growth factor. Progression-free survival correlated with
pretreatment plasma soluble mesenchymal-epithelial transition receptor and
sVEGFR1, and overall survival with the change during treatment in CD34+
progenitor/stem cells and CD8 T cells.Conclusions: Plerixafor + bevacizumab was
well tolerated in HGG patients. Plerixafor distributed to both the CSF and brain
tumor tissue, and treatment was associated with biomarker changes consistent with
VEGF and CXCR4 inhibition. Clin Cancer Res; 24(19); 4643-9. (c)2018 AACR.
PMID- 29941487
TI - The proneural bHLH genes Mash1, Math3 and NeuroD are required for pituitary
development.
AB - Multiple signaling molecules and transcription factors are required for pituitary
development. Activator-type bHLH genes Mash1, Math, NeuroD and Neurogenin are
well known as key molecules in neural development. Although analyses of targeted
mouse mutants have demonstrated involvement of these bHLH genes in pituitary
development, studies with single-mutant mice could not elucidate their exact
functions, because they cooperatively function and compensate each other. The aim
of this study was to elucidate the roles of Mash1, Math3 and NeuroD in pituitary
development. Mash1;Math3;NeuroD triple-mutant mice were analyzed by
immunohistochemistry and quantitative real time RT-PCR. Misexpression studies
with retroviruses in pituisphere cultures were also performed. The triple-mutant
adenohypophysis was morphologically normal, though the lumen of the
neurohypophysis remained unclosed. However, in triple-mutant pituitaries,
somatotropes, gonadotropes and corticotropes were severely decreased, whereas
lactotropes were increased. Misexpression of Mash1 alone with retrovirus could
not induce generation of hormonal cells, though Mash1 was involved in
differentiation of pituitary progenitor cells. These data suggest that Mash1,
Math3 and NeuroD cooperatively control the timing of pituitary progenitor cell
differentiation, and that they are also required for subtype specification of
pituitary hormonal cells. Mash1 is necessary for corticotroph and gonadotroph
differentiation, and compensated by Math3 and NeuroD. Math3 is necessary for
somatotroph differentiation, and compensated by Mash1 and NeuroD. Neurogenin2 may
compensate Mash1, Math3 and NeuroD during pituitary development. Furthermore,
Mash1, Math3 and NeuroD are required for neurohypophysis development. Thus,
Mash1, Math3 and NeuroD are required for pituitary development, and compensate
each other.
PMID- 29941489
TI - Military Prehospital Emergency Care: defining and professionalising the levels of
care provided along the Operational Patient Care Pathway.
AB - The Defence Medical Services aims to provide gold standard care to ill and
injured personnel in the deployed environment and its prehospital emergency care
(PHEC) systems have been proven to save lives. The authors have set out to
demonstrate, using existing literature, consensus and doctrine that the NHS
Skills for Health framework can be reflected in military prehospital care and
provides an existing model for defining the levels of care our providers can
offer. In addition, we have demonstrated how these levels of care support the
Operational Patient Care Pathway and add to the body of evidence for the use of
specialist PHEC teams to allow the right patient to be transported on the right
platform, with the right medical team, to the right place. These formalised
levels allow military planners to consider the scope of practice, amount of
training and appropriate equipment required to support deployed operations.
PMID- 29941488
TI - Ovarian and Extra-Ovarian Mediators in the Development of Polycystic Ovary
Syndrome.
AB - Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting
women of reproductive age. The origin of PCOS is still not clear and appears to
be a function of gene x environment interactions. This review addresses the
current knowledge of the genetic and developmental contributions to the etiology
of PCOS, the ovarian and extra-ovarian mediators of PCOS and the gaps and key
challenges that need to be addressed in the diagnosis, treatment and prevention
of PCOS.
PMID- 29941490
TI - O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells
by Stabilizing NRF1.
AB - Cancer cells often heavily depend on the ubiquitin-proteasome system (UPS) for
their growth and survival. Irrespective of their strong dependence on the
proteasome activity, cancer cells, except for multiple myeloma, are mostly
resistant to proteasome inhibitors. A major cause of this resistance is the
"proteasome bounce-back response" mediated by NRF1, a transcription factor that
coordinately activates proteasome subunit genes. To identify new targets for
efficient suppression of UPS, we explored using immunoprecipitation and mass
spectrometry the possible existence of nuclear proteins that co-operate with NRF1
and identified O-GlcNAc transferase (OGT) and Host Cell Factor C1 (HCF-1) as two
proteins capable of forming a complex with NRF1. O-GlcNAcylation catalyzed by OGT
was essential for NRF1 stabilization and consequent upregulation of proteasome
subunit genes. Meta-analysis of breast and colorectal cancers revealed positive
correlations in the relative protein abundance of OGT and proteasome subunits.
OGT inhibition was effective at sensitizing cancer cells to a proteasome
inhibitor both in culture cells and a xenograft mouse model. Since active O
GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel
linkage between cancer metabolism and UPS function and added a new regulatory
axis to the regulation of the proteasome activity.
PMID- 29941491
TI - Centromere Biology: Transcription Goes on Stage.
AB - Accurate chromosome segregation is a fundamental process in cell biology. During
mitosis, chromosomes are segregated into daughter cells through interactions
between centromeres and microtubules in the mitotic spindle. Centromere domains
have evolved to nucleate formation of the kinetochore, which is essential for
establishing connections between chromosomal DNA and microtubules during mitosis.
Centromeres are typically formed on highly repetitive DNA that is not conserved
in sequence or size among organisms and can differ substantially between
individuals within the same organism. However, transcription of repetitive DNA
has emerged as a highly conserved property of the centromere. Recent work has
shown that both the topological effect of transcription on chromatin and the
nascent noncoding RNAs contribute to multiple aspects of centromere function. In
this review, we discuss the fundamental aspects of centromere transcription,
i.e., its dual role in chromatin remodeling/CENP-A deposition and kinetochore
assembly during mitosis, from a cell cycle perspective.
PMID- 29941494
TI - The NHS is no longer safe for patients and staff, say doctors.
PMID- 29941492
TI - Modulation of Heat Shock Factor 1 Activity through Silencing of Ser303/Ser307
Phosphorylation Supports a Metabolic Program Leading to Age-Related Obesity and
Insulin Resistance.
AB - Activation of the adaptive response to cellular stress orchestrated by heat shock
factor 1 (HSF1), which is an evolutionarily conserved transcriptional regulator
of chaperone response and cellular bioenergetics in diverse model systems, is a
central feature of organismal defense from environmental and cellular stress.
HSF1 activity, induced by proteostatic, metabolic, and growth factor signals, is
regulated by posttranscriptional modifications, yet the mechanisms that regulate
HSF1 and particularly the functional significance of these modifications in
modulating its biological activity in vivo remain unknown. HSF1 phosphorylation
at both Ser303 (S303) and Ser307 (S307) has been shown to repress HSF1
transcriptional activity under normal physiological growth conditions. To
determine the biological relevance of these HSF1 phosphorylation events, we
generated a knock-in mouse model in which S303 and S307 were replaced with
alanine (HSF1303A/307A). Our results confirmed that loss of phosphorylation in
HSF1303A/307A cells and tissues increases protein stability but also markedly
sensitizes HSF1 activation under normal and heat- or nutrient-induced stress
conditions. Interestingly, the enhanced HSF1 activation in HSF1303A/307A mice
activates a supportive metabolic program that aggravates the development of age
dependent obesity, fatty liver diseases, and insulin resistance. Thus, these
findings highlight the importance of a posttranslational mechanism (through
phosphorylation at S303 and S307 sites) of regulation of the HSF1-mediated
transcriptional program that moderates the severity of nutrient-induced metabolic
diseases.
PMID- 29941493
TI - Metformin exposure in first trimester of pregnancy and risk of all or specific
congenital anomalies: exploratory case-control study.
AB - OBJECTIVE: To investigate whether exposure to metformin during the first
trimester of pregnancy, for diabetes or other indications, increases the risk of
all or specific congenital anomalies. DESIGN: Population based exploratory case
control study using malformed controls. Cases of 29 specific subgroups of non
genetic anomalies, and all non-genetic anomalies combined, were compared with
controls (all other non-genetic anomalies or genetic syndromes). SETTING: 11
EUROmediCAT European congenital anomaly registries surveying 1 892 482 births in
Europe between 2006 and 2013. PARTICIPANTS: 50 167 babies affected by congenital
anomaly (41 242 non-genetic and 8925 genetic) including live births, fetal deaths
from 20 weeks' gestation, and terminations of pregnancy for fetal anomaly. MAIN
OUTCOME MEASURE: Odds ratios adjusted for maternal age, registry, multiple birth,
and maternal diabetes status. RESULTS: 168 babies affected by congenital anomaly
(141 non-genetic and 27 genetic) were exposed to metformin, 3.3 per 1000 births.
No evidence was found for a higher proportion of exposure to metformin during the
first trimester among babies with all non-genetic anomalies combined compared
with genetic controls (adjusted odds ratio 0.84, 95% confidence interval 0.55 to
1.30). The only significant result was for pulmonary valve atresia (adjusted odds
ratio 3.54, 1.05 to 12.00, compared with non-genetic controls; 2.86, 0.79 to
10.30, compared with genetic controls). CONCLUSIONS: No evidence was found for an
increased risk of all non-genetic congenital anomalies combined following
exposure to metformin during the first trimester, and the one significant
association was no more than would be expected by chance. Further surveillance is
needed to increase sample size and follow up the cardiac signal, but these
findings are reassuring given the increasing use of metformin in pregnancy.
PMID- 29941496
TI - Acute Effect of Empagliflozin on Fractional Excretion of Sodium and eGFR in Youth
With Type 2 Diabetes.
PMID- 29941495
TI - Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A
Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts.
AB - OBJECTIVE: To describe baseline characteristics of the Vitamin D and Type 2
Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to
apply current American Diabetes Association (ADA) criteria for prediabetes.
RESEARCH DESIGN AND METHODS: This is a multicenter (n = 22 sites), randomized,
double-blind, placebo-controlled, primary prevention clinical trial testing
effects of oral daily 4,000 IU cholecalciferol (D3) compared with placebo on
incident diabetes in U.S. adults at risk for diabetes. Eligible participants were
at risk for diabetes, defined as not meeting criteria for diabetes but meeting at
least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose
(FPG) 100-125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load
140-199 mg/dL, and/or a hemoglobin A1c (HbA1c) 5.7-6.4% (39-46 mmol/mol).
RESULTS: A total of 2,423 participants (45% of whom were women and 33% nonwhite)
were randomized to cholecalciferol or placebo. Mean (SD) age was 59 (9.9) years
and BMI 32 (4.5) kg/m2. Thirty-five percent met all three prediabetes criteria,
49% met the FPG/HbA1c criteria only, 9.5% met the 2hPG/FPG criteria only, and
6.3% met the 2hPG/HbA1c criteria only. Black participants had the highest mean
HbA1c and lowest FPG concentration compared with white, Asian, and other races (P
< 0.01); 2hPG concentration did not differ among racial groups. When compared
with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG
concentration but similar HbA1c and FPG concentrations. CONCLUSIONS: D2d will
establish whether vitamin D supplementation lowers risk of diabetes and will
inform about the natural history of prediabetes per contemporary ADA criteria.
PMID- 29941497
TI - Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or
Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic
Clamp.
AB - OBJECTIVE: To compare insulin sensitivity (M/I) and beta-cell responses in youth
versus adults with impaired glucose tolerance (IGT) or drug-naive, recently
diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: In 66 youth (80.3% with
IGT) and 355 adults (70.7% IGT), hyperglycemic clamps were used to measure 1)
M/I, 2) acute (0-10 min [first phase]) C-peptide (ACPRg) and insulin (AIRg)
responses to glucose, 3) steady-state C-peptide and insulin concentrations at
plasma glucose of 11.1 mmol/L, and 4) arginine-stimulated maximum C-peptide
(ACPRmax) and insulin (AIRmax) responses at plasma glucose >25 mmol/L. The
fasting C-peptide-to-insulin ratio was used as an estimate of insulin clearance.
RESULTS: Insulin sensitivity was 46% lower in youth compared with adults (P <
0.001), and youth had greater acute and steady-state C-peptide (2.3- and 1.3
fold, respectively; each P < 0.001) and insulin responses to glucose (AIRg 3.0
fold and steady state 2.2-fold; each P < 0.001). Arginine-stimulated C-peptide
and insulin responses were also greater in youth (1.6- and 1.7-fold,
respectively; each P < 0.001). After adjustment for insulin sensitivity, all beta
cell responses remained significantly greater in youth. Insulin clearance was
reduced in youth (P < 0.001). Participants with diabetes had greater insulin
sensitivity (P = 0.026), with lesser C-peptide and insulin responses than those
with IGT (all P < 0.001) but similar insulin clearance (P = 0.109). CONCLUSIONS:
In people with IGT or recently diagnosed diabetes, youth have lower insulin
sensitivity, hyperresponsive beta-cells, and reduced insulin clearance compared
with adults. Whether these age-related differences contribute to declining beta
cell function and/or impact responses to glucose-lowering interventions remains
to be determined.
PMID- 29941499
TI - Can We RISE to the Challenge of Youth-Onset Type 2 Diabetes?
PMID- 29941498
TI - Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or
Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose
Tolerance Test.
AB - OBJECTIVE: To compare oral glucose tolerance test (OGTT) glucose, C-peptide, and
insulin responses and insulin sensitivity in youth and adults with impaired
glucose tolerance (IGT) or recently diagnosed type 2 diabetes. RESEARCH DESIGN
AND METHODS: A total of 66 youth (80.3% with IGT) and 355 adults (70.7% with IGT)
underwent a 3-h OGTT to assess 1) insulin sensitivity (1/fasting insulin), 2) C
peptide index (CPI) and insulinogenic index (IGI) over the first 30 min, and 3)
glucose, C-peptide, and insulin incremental areas above fasting over the 3-h post
ingestion (incremental glucose [G-iAUC], incremental C-peptide [CP-iAUC], and
incremental insulin area under the curve [I-iAUC] responses, respectively).
RESULTS: Fasting, 2-h glucose, and G-iAUC were similar in both age-groups, but
youth had ~50% lower 1/fasting insulin (P < 0.001), 75% higher CPI (mean [95% CI]
0.703 [0.226, 2.183] vs. 0.401 [0.136, 1.183] nmol/mmol; P < 0.001), and more
than twofold higher IGI (257.3 [54.5, 1,215.8] vs. 114.8 [28.0, 470.8] pmol/mmol;
P < 0.001). Two-hour C-peptide and insulin concentrations, CP-iAUC, and I-iAUC
were all higher in youth (all P < 0.001). C-peptide and insulin responses
remained significantly greater in youth after adjustment for insulin sensitivity.
Within each age-group, individuals with type 2 diabetes versus IGT had
significantly lower CPI and IGI with no difference in insulin sensitivity.
CONCLUSIONS: The balance between insulin sensitivity and beta-cell responses
differs between youth and adults with IGT or recently diagnosed type 2 diabetes.
Despite similar postload glucose levels, youth demonstrate greater C-peptide and
insulin responses that exceed what is needed to compensate for their lower
insulin sensitivity. Longitudinal studies are required to determine whether this
feature contributes to a more rapid decline in beta-cell function in youth with
dysglycemia.
PMID- 29941501
TI - Doctor who hid his HIV status for fear of stigma gets suspended sentence.
PMID- 29941502
TI - Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice.
AB - Endotoxemia has been recognized to be closely accompanied with type 2 diabetes
mellitus (T2DM) and is responsible for many diabetic complications. Recent study
suggests the potential role of butyrate, a short-chain fatty acid (SCFA) from
microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia.
To investigate if butyrate could ameliorate diabetic-endotoxemia, both in vivo
and in vitro experiments were carried out in the present study. The effect of
butyrate supplementation on blood HbA1c and inflammatory cytokines were
determined in db/db mice; gut barrier integrity and expression of tight junction
proteins were investigated both in vivo and in vitro Oral butyrate administration
significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db
mice; inflammatory cell infiltration was reduced, and gut integrity and
intercellular adhesion molecules were increased as detected by HE staining,
immunohistochemistry and Western blot. By gut microbiota assay, ratio of
Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2
cells, butyrate significantly promoted cell proliferation, decreased inflammatory
cytokines' secretion, enhanced cell anti-oxidative stress ability and preserved
the epithelial monocellular integrity, which was damaged by LPS. The present
findings demonstrated that butyrate supplementation could ameliorate diabetic
endotoxemia in db/db mice via restoring composition of gut microbiota and
preserving gut epithelial barrier integrity.
PMID- 29941503
TI - Igf3 activates beta-catenin signaling to stimulate spermatogonial differentiation
in zebrafish.
AB - Follicle-stimulating hormone (Fsh) is a major regulator of spermatogenesis,
targeting somatic cell functions in the testes. We reported previously that
zebrafish Fsh promoted the differentiation of type A undifferentiated
spermatogonia (Aund) by stimulating the production of factors that advance germ
cell differentiation, such as androgens, insulin-like peptide 3 (Insl3) and
insulin-like growth factor 3 (Igf3). In addition, Fsh also modulated the
transcript levels of several other genes, including some belonging to the Wnt
signaling pathway. Here, we evaluated if and how Fsh utilizes part of the
canonical Wnt pathway to regulate the development of spermatogonia. We quantified
the proliferation activity and relative section areas occupied by Aund and type A
differentiating (Adiff) spermatogonia and we analyzed the expression of selected
genes in response to recombinant proteins and pharmacological inhibitors. We
found that from the three downstream mediators of Fsh activity we examined, Igf3,
but not 11-ketotestosterone or Insl3, modulated the transcript levels of two beta
catenin sensitive genes (cyclinD1 and axin2). Using a zebrafish beta-catenin
signaling reporter line, we showed that Igf3 activated beta-catenin signaling in
type A spermatogonia and that this activation did not depend on the release of
Wnt ligands. Pharmacological inhibition of the beta-catenin or of the
phosphoinositide 3-kinase (PI3K) pathways revealed that Igf3 activated beta
catenin signaling in a manner involving PI3K to promote the differentiation of
Aund to Adiff spermatogonia. This mechanism represents an intriguing example for
a pituitary hormone like Fsh using Igf signaling to recruit the evolutionary
conserved, local beta-catenin signaling pathway to regulate spermatogenesis.
PMID- 29941504
TI - Margaret McCartney: The NHS's slow decline is a preventable disease.
PMID- 29941500
TI - Impact of Insulin and Metformin Versus Metformin Alone on beta-Cell Function in
Youth With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes.
AB - OBJECTIVE: Pediatric type 2 diabetes prevalence is increasing, with beta-cell
dysfunction key in its pathogenesis. The RISE Pediatric Medication Study compared
two approaches-glargine followed by metformin and metformin alone-in preserving
or improving beta-cell function in youth with impaired glucose tolerance (IGT) or
recently diagnosed type 2 diabetes during and after therapy withdrawal. RESEARCH
DESIGN AND METHODS: Ninety-one pubertal, overweight/obese 10-19-year-old youth
with IGT (60%) or type 2 diabetes of <6 months duration (40%) were randomized to
either 3 months of insulin glargine with a target glucose of 4.4-5.0 mmol/L
followed by 9 months of metformin or to 12 months of metformin alone. beta-Cell
function (insulin sensitivity paired with beta-cell responses) was assessed by
hyperglycemic clamp at baseline, 12 months (on treatment), and 15 months (3
months off treatment). RESULTS: No significant differences were observed between
treatment groups at baseline, 12 months, or 15 months in beta-cell function, BMI
percentile, HbA1c, fasting glucose, or oral glucose tolerance test 2-h glucose
results. In both treatment groups, clamp-measured beta-cell function was
significantly lower at 12 and 15 months versus baseline. HbA1c fell transiently
at 6 months within both groups. BMI was higher in the glargine followed by
metformin versus metformin alone group between 3 and 9 months. Only 5% of
participants discontinued the interventions, and both treatments were well
tolerated. CONCLUSIONS: In youth with IGT or recently diagnosed type 2 diabetes,
neither 3 months of glargine followed by 9 months of metformin nor 12 months of
metformin alone halted the progressive deterioration of beta-cell function.
Alternate approaches to preserve beta-cell function in youth are needed.
PMID- 29941505
TI - Minimally invasive perventricular versus open surgical ventricular septal defect
closure in infants and children: a randomised clinical trial.
AB - BACKGROUND: Robust evidence is lacking regarding the clinical efficacy, safety
and cardiopulmonary performance of perventricular closure. This study
investigated the perioperative efficacy, safety and cardiorespiratory performance
of perventricular closure of perimembranous ventricular septal defects (pmVSDs).
METHODS: Operation-naive infants and young children aged 5-60 months with
isolated pmVSDs were randomised to receive either standard open surgical or
minimally invasive perventricular closure via direct entry into the ventricle
with a catheter from a subxiphoid incision. The primary outcomes included
complete closure at discharge, major and minor adverse events and the changes in
perioperative cardiorespiratory performance from baseline. Complete closure was
mainly analysed in the modified intention-to-treat (mITT) population, with
sensitivity analyses for the ITT, per-protocol (PP) and as-treated (AT)
populations (non-inferiority margin -5.0%). RESULTS: We recruited 200 patients
with pmVSDs for this study (mean age 24.38 months, range 7-58 months, 104 girls),
of whom 100 were randomly allocated to one of the study groups. The non
inferiority of perventricular to surgical closure regarding complete closure at
discharge was not shown in the ITT (absolute difference -0.010 (95% CI -0.078 to
0.058)) and mITT populations (-0.010 (95% CI -0.069 to 0.048)), but was shown in
the PP (0.010 (95% CI -0.043 to 0.062)) and AT populations (0.048 (95% CI -0.009
to 0.106)). Perventricular closure reduced the rate of compromising cardiac
haemodynamics, electrophysiological responses, cardiomyocyte viability,
respiratory mechanics, ventilatory and gas exchange function and oxygenation and
tissue perfusion compared with surgical closure (all between-group P<0.05).
CONCLUSIONS: For infants and young children with pmVSD, perventricular closure
reduced the rate of postoperative cardiorespiratory compromise compared with
surgical closure, but the non-inferiority regarding complete closure should be
interpreted in the context of the specific population. TRIAL REGISTRATION NUMBER:
NCT02794584 ;Results.
PMID- 29941506
TI - Overview of betrixaban and its role in clinical practice.
AB - PURPOSE: The role of betrixaban in the prevention of venous thromboembolism (VTE)
in acutely medically ill patients and its efficacy and safety profiles are
reviewed. SUMMARY: Acutely medically ill patients have a high risk of developing
VTE during hospitalization, and this risk continues into the postdischarge phase.
Extended-duration betrixaban therapy has been evaluated in a large clinical trial
(the APEX trial) and in a meta-analysis of pooled data on acutely medically ill
patients. These studies have shown positive outcomes when betrixaban was compared
with conventional-duration subcutaneous enoxaparin therapy for prevention of VTE
in acutely medically ill patients. In parallel with these results, oral
betrixaban therapy was found to be associated with a rate of major bleeding
comparable to that associated with subcutaneous enoxaparin therapy; however,
betrixaban use was associated with a higher cumulative rate of major and
clinically relevant nonmajor bleeding. In the APEX trial, the primary endpoint
was not met in 1 of the prespecified cohorts, but betrixaban appeared to confer
benefit in another cohort and in the overall study population. Certain
populations of patients, including the elderly, are at high risk for bleeding
(mainly attributable to altered pharmacokinetics and polypharmacy); such patients
are not appropriate candidates for extended-duration betrixaban therapy.
Betrixaban can be a potential option for VTE prevention in medical patients;
however, drug interaction potential and third-party coverage should be evaluated
prior to prescribing. CONCLUSION: Betrixaban is an oral option for VTE prevention
in medical patients.
PMID- 29941507
TI - Comparison of blood product use and costs with use of 3-factor versus 4-factor
prothrombin complex concentrate for off-label indications.
AB - PURPOSE: Results of a comparison of blood product use and cost outcomes with use
of 3-factor versus 4-factor prothrombin complex concentrate (PCC) for indications
other than warfarin reversal are presented. METHODS: Consecutive patients who
received 3-factor PPC (PCC3) or 4-factor PCC (PCC4) for non-warfarin-related
indications at 2 U.S. hospitals during a 19-month period were identified. The
primary outcome was in-hospital blood product use, with a focus on plasma use.
Total hemostasis costs, intensive care unit (ICU) and hospital lengths of stay,
and other outcomes were evaluated. RESULTS: Indications for PCC3 use (n = 118) or
PCC4 use (n = 64) included intraoperative bleeding, nonintraoperative bleeding,
coagulopathy of liver disease, and reversal of direct-acting oral anticoagulant
effects. The proportion of patients who received plasma was 56.8% with PCC3 use
versus 53.1% with PCC4 use (p = 0.643); the corresponding median volumes of
plasma received were 638 mL (interquartile range [IQR], 550-1,355 mL) and 656 mL
(IQR, 532-1,136 mL), respectively. The median total hemostasis costs were $5,559
(IQR, $3,922-$8,159) with PCC3 use and $7,771 (IQR, $6,366-$9,205) with PCC4 use
(p < 0.001). CONCLUSION: PCC3 use and PCC4 use were associated with similar blood
product use, ICU length of stay, hospital length of stay, and in-hospital
mortality when given for non-warfarin-related indications. However, relative to
PCC3 use, PCC4 use was associated with an increase in costs that was primarily
due to drug costs.
PMID- 29941508
TI - Initial study of clinical pharmacy work prioritization tools.
AB - PURPOSE: The development, implementation, and validity of clinical pharmacy work
prioritization tools (CPWPTs) were analyzed. METHODS: Informatics pharmacists
were contacted and asked to participate in 30-minute teleconference interviews,
as they have primary responsibility for the technical configuration of CPWPTs. A
total of 19 respondents participated in the survey. The qualitative data
collected encompassed the thoughts and ideas of practicing informatics
pharmacists who are knowledgeable about the design, configuration, management,
and use of CPWPTs. In addition to capturing their thoughts and ideas with open
ended questions, demographic data were collected, as was information about the
sites where respondents worked and the CPWPTs they used. RESULTS: Most of the
CPWPTs were built into existing electronic health record platforms. There was
considerable variation among the prioritization factors used at each site. The
most commonly identified categories of prioritization factors were patient
specific factors, therapeutic classes of medications, and potential pharmacist
interventions. All respondents reported that the prioritized tasks generated by
their CPWPTs were examined for face validity. Of the 19 respondents, only 4
reported that the priorities generated by their CPWPT had been empirically
validated in some way. Qualitative data analysis revealed that informatics
pharmacists have 5 general perceptions about CPWPT factors, validation, and use
in practice: (1) mirroring practice, (2) pharmacist consensus-based design, (3)
complexity of logic, (4) tension between task-oriented and patient-centric
approaches to practice, and (5) comfort from tracking tasks to completion.
CONCLUSION: Early CPWPTs vary significantly in their prioritization factors.
These tools partially reflect the scope of clinical pharmacy practice at the
sites where they are used.
PMID- 29941509
TI - "Safe spaces" for conducting healthcare failure investigations will increase
litigation, MPs hear.
PMID- 29941510
TI - Renal Denervation-Ready for Prime Time!? The Steep SPYRAL Stairs to RADIANCE in
Hypertension Treatment.
PMID- 29941511
TI - Resistant Hypertension and Obstructive Sleep Apnea: Is There a Specific
Indication for Endovascular Renal Denervation?
PMID- 29941512
TI - Natriuretic Peptides in Cardiovascular and Metabolic Crosstalk: Implications for
Hypertension Management.
PMID- 29941513
TI - Does Obstructive Sleep Apnea Influence Blood Pressure and Arterial Stiffness in
Response to Antihypertensive Treatment?
AB - Untreated obstructive sleep apnea (OSA) is common in patients with hypertension
and may impair blood pressure (BP) and target-organ damage responses to
antihypertensive therapy. In this study, we recruited hypertensive patients who
underwent treatment with a 30-day regimen of hydrochlorothiazide 25 mg plus
enalapril (20 mg BID) or losartan (50 mg BID) and were assessed with a baseline
clinical evaluation, polysomnography, 24-hour ambulatory BP monitoring, and
carotid-femoral pulse wave velocity. All the examinations except for
polysomnography were repeated at 6 and 18 months of follow-up. We studied 94
hypertensive patients (mean age, 55+/-9 years). The frequency of OSA was 55%.
Compared with baseline, we did not observe significant differences between groups
in 24-hour BP, daytime systolic and diastolic BPs, or night-time systolic BP at 6
and 18 months. The BP control rate at 24 hours (<130/80 mm Hg) was similar
between the groups (baseline, 42.3% versus 45.2%; 6 months, 46.9% versus 57.5%;
18 months, 66.7% versus 61.5%). However, patients with OSA had higher night-time
diastolic BP decrease than did the non-OSA group (6 months, -4.9+/-11.8 versus
0.3+/-10.3 mm Hg; 18 months, -6.7+/-11.1 versus -1.2+/-10.6 mm Hg; P=0.027).
There were no differences in the number and class of antihypertensive medications
prescribed during follow-up. In terms of arterial stiffness, patients with OSA
had higher pulse wave velocity than did patients without OSA at baseline (10.3+/
1.9 versus 9.2+/-1.7 m/s; P=0.024), but both groups had similar decreases in
pulse wave velocity during follow-up. In conclusion, with combined
antihypertensive treatment aimed at controlling BP, hypertensive patients with
OSA had similar 24-hour BP and arterial stiffness to those without OSA.
PMID- 29941514
TI - Adenosine Receptors: A Tantalizing Target for the Treatment of Salt-Sensitive
Hypertension.
PMID- 29941515
TI - Adenosine Receptors Influence Hypertension in Dahl Salt-Sensitive Rats:
Dependence on Receptor Subtype, Salt Diet, and Sex.
AB - The influence of adenosine receptors on blood pressure in salt-sensitive
hypertension is unknown. Here, we examined the effects of salt diets on arterial
blood pressures (radiotelemetry) in female and male Dahl salt-sensitive wild-type
versus female and male Dahl salt-sensitive A1, A2A, or A2B receptor knockouts
(A1KOs, A2AKOs, and A2BKOs, respectively). At baseline, all rats were on a 0.3%
salt diet; then separate groups were switched to either 4% or 8% salt diet for 2
weeks. Compared with wild-types, baseline pressures were not affected by knockout
of A1 or A2B receptors; yet, mean, systolic, and diastolic pressures were
significantly (P<0.01) higher in A2AKOs versus wild-types, an effect independent
of sex. During the second week on a 4% salt diet, mean, systolic, and diastolic
blood pressures (mm Hg, mean+/-SEM) in female A1KOs (176+/-5, 209+/-5, and 147+/
4, respectively) and A2BKOs (166+/-8, 198+/-9, and 139+/-8, respectively) were
significantly lower (P<0.001) than wild-type on a 4% salt diet (202+/-4, 240+/-5,
and 172+/-3, respectively). Male A1KOs and A2BKOs were not protected against 4%
salt diet-induced hypertension. This female advantage was overwhelmed by an 8%
salt diet. Female and male A2AKOs were more salt sensitive, a phenotype that was
apparent in male A2AKOs on 4% and 8% salt diets and in females on 8% salt diet.
Female A1KOs and A2BKOs were less susceptible to salt-induced stroke and
experienced improved survival. Adenosine receptors influence blood pressure and
survival in salt-sensitive rats, and the impact of deleting adenosine receptors
on blood pressure and survival depends on salt diet and sex.
PMID- 29941516
TI - Renal Denervation in Resistant Hypertension and Obstructive Sleep Apnea:
Randomized Proof-of-Concept Phase II Trial.
AB - : It has been postulated that catheter-based renal denervation (RDN) may lower
blood pressure (BP) and improve severity of obstructive sleep apnea (OSA) in
resistant hypertensive patients. The aim of our study (NCT01366625) was to
investigate in a prospective randomized trial the effect of RDN on BP and
clinical course of OSA. Sixty patients with true resistant hypertension
coexisting with moderate-to-severe OSA (apnea/hypopnea index, >=15) were randomly
allocated to RDN group (30 patients) and to control group (30 patients). The
primary end point was reduction in office systolic BP at 3 months. Secondary end
points included reduction in diastolic office and ambulatory BP, change in
apnea/hypopnea index and biochemical measurements at 3 months, and change in
echocardiographic measurements at 6 months. There were no differences in clinical
characteristics between the groups. At 3 months in the RDN group, both office and
ambulatory BP were significantly reduced, and a significant decrease in OSA
severity (apnea/hypopnea index, 39.4 versus 31.2 events per hour; P=0.015) was
observed. Between-group difference in apnea/hypopnea index change was significant
at 0.05. At 6 months in the RDN group, reductions in office and ambulatory BP
were sustained and were accompanied by significant improvement in
echocardiographic measures of global longitudinal strain. There were no
differences in metabolic variables in follow-up in both groups. In a randomized
controlled trial, RDN lowered both office and ambulatory BP in patients with
resistant hypertension and OSA. This was accompanied by improvement of the
clinical severity of OSA. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01366625.
PMID- 29941517
TI - Evaluation of Hemolysis as a Severe Feature of Preeclampsia.
AB - Hemolysis predisposes to adverse pregnancy outcomes. Yet, there are limited data
on hemolysis in hypertensive disorders of pregnancy other than hemolysis,
elevated liver enzymes, and low platelet count syndrome. To evaluate the
prevalence and impact of hemolysis in hypertensive disorders of pregnancy, we
performed a retrospective cohort study at a single center (October 2013-May
2017), among women screened for hemolysis using lactate dehydrogenase (LDH)
levels. We compared LDH levels by hypertensive disorder (chronic hypertension,
gestational hypertension, preeclampsia, and preeclampsia with severe features)
and evaluated impact on adverse pregnancy outcomes. Data were analyzed by chi2 or
t test, ANOVA, test of medians, and logistic regression. Among 8645 deliveries,
1188 (13.7%) had a hypertensive disorder. Of these, 812 (68.4%) had LDH
measurement before delivery: chronic hypertension (n=152); gestational
hypertension (n=209); preeclampsia (n=216); and preeclampsia with severe features
(n=235). LDH >=400 U/L (>=1.6* normal) was more common in preeclampsia with
severe features compared with other hypertensive disorders of pregnancy (9.8%
versus 2.3%; P<0.001); adjusted odds ratio 4.52 (95% confidence interval, 2.2
9.2; P<0.001). LDH >=400 U/L was associated with adverse maternal outcomes (41.7%
versus 15.3%; P<0.001), adjusted odds ratio 3.05 (95% confidence interval, 1.4
6.7; P=0.006), and adverse neonatal outcomes (eg, preterm birth 59.4% versus
22.5%; P<0.001). We find that elevated LDH levels are associated with adverse
maternal and neonatal outcomes in hypertension and preeclampsia, independent of
hemolysis, elevated liver enzymes, and low platelet count syndrome. Therefore,
elevated LDH levels (>=1.6* normal or >=400 U/L) may be considered a severe
feature of preeclampsia.
PMID- 29941518
TI - Impact of the Discordance Between the American College of Cardiology/American
Heart Association and American Diabetes Association Recommendations on
Hypertension in Patients With Diabetes Mellitus in the United States.
PMID- 29941519
TI - Hypertension in Blacks: Individualized Therapy Based on Renin/Aldosterone
Phenotyping.
PMID- 29941521
TI - Childhood obesity: government's plan targets energy drinks and junk food
advertising.
PMID- 29941520
TI - Renin-Angiotensin-Aldosterone Profiles in Pregnant Women With Chronic
Hypertension.
AB - Pregnant women with chronic hypertension are at risk for increased blood pressure
and superimposed preeclampsia (SPE) in late pregnancy. Alterations in the renin
aldosterone system are a feature of normal pregnancy; however, their role in
chronic hypertension with and without SPE is less clear. We performed a
prospective, longitudinal trial of 108 women with chronic hypertension and
measured plasma renin activity (PRA), 24-hour urine sodium, urine potassium, and
urine aldosterone (Ualdo) at 12, 20, 28, and 36 weeks and postpartum. SPE
developed in 34% of pregnancies. PRA was lower in women who developed SPE at
weeks 28 (5.99 versus 6.22 ng/mL per hour; P<0.001) and 36 (5.71 versus 7.74
ng/mL per hour; P=0.002). Ualdo was lower in women with SPE compared with those
without SPE at 28 weeks (59.6 versus 81.3 MUg/d; P=0.039). Mean arterial pressure
was inversely related to both PRA (r=-0.23; P<0.0001) and Ualdo (r=-0.11;
P=0.029). PRA and Ualdo were positively associated with each other (r=0.5327;
P<0.0001) after adjusting for urine potassium, urine sodium, serum potassium, and
mean arterial pressure. PRA and Ualdo were lower in women of black race compared
with other racial groups (P<0.001). Our results demonstrate that in women with
chronic hypertension PRA and Ualdo increase in early pregnancy and subsequently
decrease in women who develop SPE. These findings are consistent with the
hypothesis that sodium retention may contribute to the elevation in blood
pressure in SPE.
PMID- 29941522
TI - Adenylyl cyclase 6 is required for maintaining acid-base homeostasis.
AB - Adenylyl cyclase (AC) isoform 6 (AC6) is highly expressed throughout the renal
tubule and collecting duct (CD), catalyzes the synthesis of cAMP and contributes
to various aspects of renal transport. Several proteins involved in acid-base
homeostasis are regulated by cAMP. In the present study, we assess the relative
contribution of AC6 to overall acid-base regulation using mice with global
deletion of AC6 (AC6-/-) or newly generated mice lacking AC6 in the renal tubule
and CD (AC6loxloxPax8Cre). Higher energy expenditure in AC6-/- relative to wild
type (WT) mice, was associated with lower urinary pH, mild alkalosis in
conjunction with elevated blood HCO3- concentrations, and significantly higher
renal abundance of the H+-ATPase B1 subunit. In contrast with WT mice, AC6-/-
mice have a less pronounced increase in urinary pH after 8 days of HCO3-
challenge, which is associated with increased blood pH and HCO3- concentrations.
Immunohistochemistry demonstrated that AC6 was expressed in intercalated cells
(IC), but subcellular distribution of the H+-ATPase B1 subunit, pendrin, and the
anion exchangers 1 and 2 in AC6-/- mice was normal. In the AC6-/- mice, H+-ATPase
B1 subunit levels after HCO3- challenge were greater, which correlated with a
higher number of type A IC. In contrast with the AC6-/- mice, AC6loxloxPax8Cre
mice had normal urinary pH under baseline conditions but higher blood HCO3- than
controls after HCO3- challenge. In conclusion, AC6 is required for maintaining
normal acid-base homeostasis and energy expenditure. Under baseline conditions,
renal AC6 is redundant for acid-base balance but becomes important under alkaline
conditions.
PMID- 29941523
TI - Photo Quiz: An 85-Year-Old Man with Brain Abscess.
PMID- 29941524
TI - Answer to July 2018 Photo Quiz.
PMID- 29941525
TI - The Brief Case: An Unusual Cause of Infective Endocarditis after a Urological
Procedure.
PMID- 29941526
TI - Closing the Brief Case: An Unusual Cause of Infective Endocarditis after a
Urological Procedure.
PMID- 29941527
TI - Senators acknowledge importance of 340B program.
PMID- 29941528
TI - FDA approves nonopioid medication for managing opioid withdrawal.
PMID- 29941529
TI - Rural hospitals meet informatics challenges.
PMID- 29941530
TI - ASHP offers informatics resources for small and rural hospitals.
PMID- 29941531
TI - FDA approves licensing of erenumab-aooe to prevent migraine.
PMID- 29941532
TI - Update on preparation of solutions for continuous renal replacement therapy.
PMID- 29941533
TI - Palliative care pharmacist interventions in a community hospital.
PMID- 29941534
TI - Successful treatment of ventriculitis caused by Pseudomonas aeruginosa and
carbapenem-resistant Klebsiella pneumoniae with i.v. ceftazidime-avibactam and
intrathecal amikacin.
AB - PURPOSE: A patient with carbapenem-resistant Klebsiella pneumoniae infection is
described, and treatment options are discussed. SUMMARY: Few antibiotics to treat
carbapenem-resistant Enterobacteriaceae (CRE) infection are available, and
treatment is further complicated by the limited ability of many antibiotics to
penetrate into the cerebrospinal fluid (CSF). Currently, there is a lack of
clinical data on the treatment of central nervous system CRE infections, and
therapy is based on case reports, case series, and small retrospective studies. A
patient was admitted to the emergency department with intracranial hemorrhage and
ventriculitis due to traumatic injury. A ventriculostomy and, subsequently, a
ventriculoperitoneal (VP) shunt were placed. After approximately a month of
treatment with various antibiotic regimens, the patient's VP shunt was
externalized, and a CSF culture speciated carbapenem-resistant K. pneumoniae and
Pseudomonas aeruginosa. The patient was then switched to i.v. ceftazidime
avibactam and intrathecal amikacin therapy. His CSF cultures were sterile 3 days
after initiation of those antibiotics, and subsequent CSF cultures resulted in no
growth. After the patient was treated with intrathecal amikacin 30 mg daily for 4
weeks and i.v. ceftazidime-avibactam 2.5 g every 8 hours for 6 weeks, the
ventriculitis resolved, the external ventricular drain was removed, and he was
transferred to a long-term care facility for rehabilitation. CONCLUSION: A man
with ventriculitis caused by P. aeruginosa and carbapenem-resistant K. pneumoniae
was successfully treated with i.v. ceftazidime-avibactam and intrathecal
amikacin.
PMID- 29941535
TI - Treatment of Aspergillus fumigatus infection with posaconazole delayed-release
tablets.
AB - PURPOSE: A pediatric patient with cystic fibrosis (CF) was successfully treated
for Aspergillus fumigatus infection with posaconazole delayed-release tablets.
SUMMARY: A 13-year-old, 29-kg, Caucasian boy with CF was admitted to the hospital
for a pulmonary exacerbation. The patient had a history of multiple hospital
admissions and was colonized with methicillin-sensitive Staphylococcus aureus,
Stenotrophomonas maltophilia, and A. fumigatus. The patient was started on
piperacillin-tazobactam 2.8 g (piperacillin 2 g and tazobactam 0.8 g) i.v. every
6 hours (400 mg/kg/day) and tobramycin 400 mg i.v. every 24 hours (13.7
mg/kg/day). After 2 weeks of therapy and therapeutic tobramycin concentrations,
doxycycline 75 mg given orally twice daily was continued due to lack of clinical
improvement. After 2 additional weeks of therapy, the patient was started on
posaconazole delayed-release tablets 300 mg given orally daily with the evening
meal due to concern about A. fumigatus colonization and a further decline in
forced expiratory volume in 1 second to 37%. The posaconazole trough
concentration was 1,500 ng/mL after 5 days of therapy. As this level was within
the goal range, posaconazole was continued, with a plan to periodically check the
trough level, pulmonary function, and liver function. The patient's liver
function values remained stable throughout therapy. The patient's appetite
improved and weight increased. Once the patient's weight exceeded 35 kg, his
dosage of posaconazole delayed-release tablets was increased to 400 mg daily. His
pulmonary function improved during posaconazole therapy, and A. fumigatus was
eradicated. Posaconazole was discontinued after 9 months of therapy. CONCLUSION:
A 13-year old patient with CF was successfully treated for an A. fumigatus
infection with posaconazole delayed-release tablets.
PMID- 29941536
TI - Expansion of clinical pharmacist positions through sustainable funding.
AB - PURPOSE: Expansion of clinical pharmacist positions through sustainable funding
is described. SUMMARY: The University of Colorado Skaggs School of Pharmacy and
Pharmaceutical Sciences was awarded a 2-year program grant to establish an
integrated clinical pharmacy program for underserved residents in family health
centers in northeastern Colorado. The grant enabled the hiring of 2 bilingual,
full-time, board-certified, postgraduate year 2-trained clinical pharmacists to
initiate comprehensive clinical pharmacy services. Clinical pharmacy services for
diabetes, hypertension, and dyslipidemia management were provided during direct
patient care visits using collaborative drug therapy management protocols to
facilitate comprehensive medication management. Initial visits lasted 1 hour, and
follow-up visits lasted 30 minutes. In addition, clinical pharmacists provided
point-of-care consultations for patients seeing other healthcare providers. All
patient encounters and consultations were documented in the electronic health
record. Success of the clinical pharmacy program was evaluated based on the
achievement of goal blood pressure values, glycosylated hemoglobin values, and
low-density-lipoprotein cholesterol levels. Pharmacists' involvement in patient
care activities led to improvements in all of these clinical outcomes. This
coincided with unique funding opportunities with regional accountable care
organizations that sought to demonstrate improved patient care in an expansion
population. As a result, 2 grant-funded clinical pharmacist positions in 2
community health clinics were converted into 4 faculty positions in 5 community
health centers funded by regional accountable care organizations. CONCLUSION:
Collaboration with accountable care organizations resulted in the successful
funding of ambulatory care clinical pharmacy services. These services resulted in
improved chronic disease control and provider satisfaction.
PMID- 29941537
TI - Impact of the clinical pharmacy specialist in telehealth primary care.
AB - PURPOSE: A telehealth-based chronic disease management program including clinical
pharmacy specialists (CPSs) and the program's impact on primary care outcomes in
a population of veterans are described. SUMMARY: A telehealth program including
CPS services was developed to improve healthcare access and quality for veterans
in rural areas of the Pacific Northwest. Outcomes of medication management
services provided by a CPS team during both clinical video telehealth and
telephone encounters with 554 patients from October 2014 to March 2017 were
assessed. Patients were targeted for diabetes (DM), hyperlipidemia (HLD), and
hypertension (HTN) control and tobacco cessation; the respective primary outcomes
were the mean changes from baseline in glycosylated hemoglobin (HbA1c) and blood
pressure values and rates of guideline-indicated statin therapy and tobacco
cessation. Patients in the DM and HTN groups had a mean absolute HbA1c reduction
of 1.61% (95% confidence interval [CI], 1.39-1.83%; p < 0.0001) and a mean
systolic blood pressure reduction of 26.00 mm Hg (95% CI, 22.99-28.50 mm Hg; p <
0.001), respectively. In the HLD group, 93% of patients were discharged on a
lipid-lowering medication. Tobacco cessation was achieved in 42% of targeted
patients. CONCLUSION: CPSs providing primary care comprehensive medication
management services solely via telehealth improved disease management and access
to healthcare in a population of rural veterans. Statistically significant
improvements in DM and HTN outcomes were demonstrated along with clinically
significant improvements in the areas of lipid management and tobacco cessation.
PMID- 29941538
TI - ASHP Practitioner Recognition Program-2018 Fellows of the American Society of
Health-System Pharmacists.
PMID- 29941540
TI - NHS funding boost is "well short of what's needed" to improve care, BMA chair
warns.
PMID- 29941541
TI - Soluble stroma-related biomarkers of pancreatic cancer.
AB - The clinical management of pancreatic ductal adenocarcinoma (PDAC) is hampered by
the lack of reliable biomarkers. This study investigated the value of soluble
stroma-related molecules as PDAC biomarkers. In the first exploratory phase, 12
out of 38 molecules were associated with PDAC in a cohort of 25 PDAC patients and
16 healthy subjects. A second confirmatory phase on an independent cohort of 131
PDAC patients, 30 chronic pancreatitis patients, and 131 healthy subjects
confirmed the PDAC association for MMP7, CCN2, IGFBP2, TSP2, sICAM1, TIMP1, and
PLG Multivariable logistic regression model identified biomarker panels
discriminating respectively PDAC versus healthy subjects (MMP7 + CA19.9, AUC =
0.99, 99% CI = 0.98-1.00) (CCN2 + CA19.9, AUC = 0.96, 99% CI = 0.92-0.99) and
PDAC versus chronic pancreatitis (CCN2 + PLG+FN+Col4 + CA19.9, AUC = 0.94, 99% CI
= 0.88-0.99). Five molecules were associated with PanIN development in two GEM
models of PDAC (PdxCre/LSL-KrasG12D and PdxCre/LSL-KrasG12D/+/LSL-Trp53R172H/+),
suggesting their potential for detecting early disease. These markers were also
elevated in patient-derived orthotopic PDAC xenografts and associated with
response to chemotherapy. The identified stroma-related soluble biomarkers
represent potential tools for PDAC diagnosis and for monitoring treatment
response of PDAC patients.
PMID- 29941543
TI - Ten tips for spotting industry involvement in science policy.
PMID- 29941542
TI - Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut
inflammation.
AB - Post-translational modifications in intestinal epithelial cells (IECs) allow for
precise control in intestinal homeostasis, the breakdown of which may precipitate
the pathological damage and inflammation in inflammatory bowel disease. The O
linked beta-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins
controls diverse biological processes; however, its roles in intestinal
homeostasis are still largely unexplored. Here, we found that levels of protein O
GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding
the O-GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT
specifically in IECs resulted in disrupted epithelial barrier, microbial
dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using
fecal microbiota transplantation in mice, we demonstrated that microbial
dysbiosis although was insufficient to induce spontaneous inflammation but
exacerbated chemical-induced colitis. Paneth cell-specific deletion of OGT led to
Paneth cell dysfunction, which might predispose mice to chemical-induced colitis.
On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O
GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced
colitis. Our data reveal that protein O-GlcNAcylation in IECs controls key
regulatory mechanisms to maintain mucosal homeostasis.
PMID- 29941544
TI - Brussels Declaration: a vehicle for the advancement of tobacco and alcohol
industry interests at the science/policy interface?
AB - The case for policies to be based on evidence appeared to gain a major boost with
the publication of the Brussels Declaration, apparently with support from many
leading scientists and institutions. Yet, as we show in this analysis, there are
major concerns about how it was developed and, in particular, the extensive
involvement of tobacco and alcohol industry actors. We describe how its coverage
of conflicts of interest and vested interests is consistent with the perspectives
of these same actors. The process of developing the Declaration successfully
involved science advisors, other senior officials in governments and politicians
in its preparation. Despite this, the final Declaration fails to address the need
for safeguards to protect the integrity of science or policy from corporate
interests, including in relation to the tobacco industry. This undermines Article
5.3 of the Framework Convention on Tobacco Control which seeks to protect public
health policies from interference by the tobacco companies. More broadly, the
Declaration offers potential to serve as a vehicle for advancing the vested
interests of corporate sectors in public policymaking and appears to have been
regarded in this way by a range of organisations related to the alcohol industry.
This exercise is now being extended to the continent of Africa, which is
strategically important to both the tobacco and alcohol industries. It will be
important to study carefully to what extent initiatives like this form part of
the global political strategies of tobacco and alcohol industry actors.
PMID- 29941545
TI - Special Sections for the 6th ASM Conference on Cell-Cell Communication in
Bacteria.
PMID- 29941546
TI - Evaluation of liver test abnormalities in a patient-centered medical home: do
liver test patterns matter?
AB - Abnormal liver tests are extremely common in clinical practice, present with
varying patterns and degrees of elevation, and can signal liver injury from a
variety of causes. Responding to these abnormalities requires complex medical
decision-making and merits investigation in primary care. This retrospective
study investigates the association of patterns of liver test abnormality with
follow-up in primary care. Using administrative data, this study includes
patients with abnormal liver tests seen between 2007 and 2016 in a patient
centered medical home. Liver tests examined include serum bilirubin, aspartate
aminotransferase, alanine aminotransferase, and alkaline phosphatase. Patients
entered the cohort on the first liver test elevation. The outcome examined was
completion of repeat testing, and the proportions of patients without follow-up
were compared by patterns of index abnormality. 9545 patients met the inclusion
criteria. Of these, 6155 (64.5%) possessed one liver test abnormality and 3390
(35.5%) possessed multiple abnormalities on index testing. Overall 1119 (11.7%)
patients did not have repeat testing performed during the study period. A greater
proportion of patients with lone abnormalities lacked repeat testing compared
with those patients with multiple abnormalities. Differences in repeat testing
appeared when comparing clinical patterns of abnormality, with higher proportions
of follow-up in patients with testing suggestive of cholestasis. Over 11% of
patients with abnormal liver tests did not undergo repeat testing during the
study period. Repeat testing occurred more often in patients with multiple
abnormalities and in clinical patterns suggestive of cholestasis. This study
highlights a potential opportunity to improve quality of care.
PMID- 29941547
TI - Checkpoint inhibitors in head and neck cancer: current knowledge and
perspectives.
AB - The emergence of immunotherapy has provided significant clinical improvements in
the treatment of metastatic solid tumors. Recurrent/metastatic head and neck
squamous cell carcinoma (HNSCC) has dismal prognosis with median survival ranging
between 6and12 months. Our aim is to review the current knowledge on the role of
the immune system and immune checkpoint inhibitors in HNSCC. We will focus on the
landmark trials that led to the regulatory approvals of pembrolizumab and
nivolumab, and discuss a few promising contenders in clinical development and
highlight the need to identify better biomarkers other than programmed death
ligand 1 to improve patient selection and help predict response.
PMID- 29941548
TI - Neuronal integrity and complement control synaptic material clearance by
microglia after CNS injury.
AB - Phagocytosis of synaptic material by microglia is critical for central nervous
system development. Less well understood is this microglial function in the
injured adult brain. Assay of microglial phagocytosis is challenging, because
peripheral myeloid cells engraft the site of injury, which could obscure
interpretation of microglial roles. The model used here, optic nerve crush
injury, results in degeneration of synapses in the dorsal lateral geniculate
nucleus (dLGN), which stimulates rapid activation and engulfment of synaptic
material by resident microglia without myeloid cell engraftment. Pharmacological
depletion of microglia causes postinjury accumulation of synaptic debris,
suggesting that microglia are the dominant postinjury phagocytes. Genetic or
pharmacological manipulations revealed that neuronal activity does not trigger
microglia phagocytosis after injury. RNA sequencing reveals C1q and CD11b/CR3
involvement in clearance of debris by dLGN-resident microglia. Indeed, C1qa-/-
and Itgam-/- mice exhibit impaired postinjury debris clearance. Our results show
how neurodegenerative debris is cleared by microglia and offers a model for
studying its mechanisms and physiological roles.
PMID- 29941549
TI - JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic
leukemia.
AB - A substantial subset of patients with T cell acute lymphoblastic leukemia (T-ALL)
develops resistance to steroids and succumbs to their disease. JDP2 encodes a
bZIP protein that has been implicated as a T-ALL oncogene from insertional
mutagenesis studies in mice, but its role in human T-ALL pathogenesis has
remained obscure. Here we show that JDP2 is aberrantly expressed in a subset of T
ALL patients and is associated with poor survival. JDP2 is required for T-ALL
cell survival, as its depletion by short hairpin RNA knockdown leads to
apoptosis. Mechanistically, JDP2 regulates prosurvival signaling through direct
transcriptional regulation of MCL1. Furthermore, JDP2 is one of few oncogenes
capable of initiating T-ALL in transgenic zebrafish. Notably, thymocytes from
rag2:jdp2 transgenic zebrafish express high levels of mcl1 and demonstrate
resistance to steroids in vivo. These studies establish JDP2 as a novel oncogene
in high-risk T-ALL and implicate overexpression of MCL1 as a mechanism of steroid
resistance in JDP2-overexpressing cells.
PMID- 29941550
TI - Aerosol microdroplets exhibit a stable pH gradient.
AB - Suspended aqueous aerosol droplets (<50 um) are microreactors for many important
atmospheric reactions. In droplets and other aquatic environments, pH is arguably
the key parameter dictating chemical and biological processes. The nature of the
droplet air/water interface has the potential to significantly alter droplet pH
relative to bulk water. Historically, it has been challenging to measure the pH
of individual droplets because of their inaccessibility to conventional pH
probes. In this study, we scanned droplets containing 4-mercaptobenzoic acid
functionalized gold nanoparticle pH nanoprobes by 2D and 3D laser confocal Raman
microscopy. Using surface-enhanced Raman scattering, we acquired the pH
distribution inside approximately 20-um-diameter phosphate-buffered aerosol
droplets and found that the pH in the core of a droplet is higher than that of
bulk solution by up to 3.6 pH units. This finding suggests the accumulation of
protons at the air/water interface and is consistent with recent thermodynamic
model results. The existence of this pH shift was corroborated by the observation
that a catalytic reaction that occurs only under basic conditions (i.e.,
dimerization of 4-aminothiophenol to produce dimercaptoazobenzene) occurs within
the high pH core of a droplet, but not in bulk solution. Our nanoparticle probe
enables pH quantification through the cross-section of an aerosol droplet,
revealing a spatial gradient that has implications for acid-base-catalyzed
atmospheric chemistry.
PMID- 29941551
TI - Symmetric shear banding and swarming vortices in bacterial superfluids.
AB - Bacterial suspensions-a premier example of active fluids-show an unusual response
to shear stresses. Instead of increasing the viscosity of the suspending fluid,
the emergent collective motions of swimming bacteria can turn a suspension into a
superfluid with zero apparent viscosity. Although the existence of active
superfluids has been demonstrated in bulk rheological measurements, the
microscopic origin and dynamics of such an exotic phase have not been
experimentally probed. Here, using high-speed confocal rheometry, we study the
dynamics of concentrated bacterial suspensions under simple planar shear. We find
that bacterial superfluids under shear exhibit unusual symmetric shear bands,
defying the conventional wisdom on shear banding of complex fluids, where the
formation of steady shear bands necessarily breaks the symmetry of unsheared
samples. We propose a simple hydrodynamic model based on the local stress balance
and the ergodic sampling of nonequilibrium shear configurations, which
quantitatively describes the observed symmetric shear-banding structure. The
model also successfully predicts various interesting features of swarming
vortices in stationary bacterial suspensions. Our study provides insights into
the physical properties of collective swarming in active fluids and illustrates
their profound influences on transport processes.
PMID- 29941552
TI - Large-scale replicated field study of maize rhizosphere identifies heritable
microbes.
AB - Soil microbes that colonize plant roots and are responsive to differences in
plant genotype remain to be ascertained for agronomically important crops. From a
very large-scale longitudinal field study of 27 maize inbred lines planted in
three fields, with partial replication 5 y later, we identify root-associated
microbiota exhibiting reproducible associations with plant genotype. Analysis of
4,866 samples identified 143 operational taxonomic units (OTUs) whose variation
in relative abundances across the samples was significantly regulated by plant
genotype, and included five of seven core OTUs present in all samples. Plant
genetic effects were significant amid the large effects of plant age on the
rhizosphere microbiome, regardless of the specific community of each field, and
despite microbiome responses to climate events. Seasonal patterns showed that the
plant root microbiome is locally seeded, changes with plant growth, and responds
to weather events. However, against this background of variation, specific taxa
responded to differences in host genotype. If shown to have beneficial functions,
microbes may be considered candidate traits for selective breeding.
PMID- 29941553
TI - Ionic liquids for oral insulin delivery.
AB - With the rise in diabetes mellitus cases worldwide and lack of patient adherence
to glycemia management using injectable insulin, there is an urgent need for the
development of efficient oral insulin formulations. However, the gastrointestinal
tract presents a formidable barrier to oral delivery of biologics. Here we report
the development of a highly effective oral insulin formulation using choline and
geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport
of insulin, while protecting it from enzymatic degradation and by interacting
with the mucus layer resulting in its thinning. In vivo, insulin-CAGE
demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after
jejunal administration in rats. Low insulin doses (3-10 U/kg) brought about a
significant decrease in blood glucose levels, which were sustained for longer
periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE
was orally delivered in enterically coated capsules using an oral gavage, a
sustained decrease in blood glucose of up to 45% was observed. The formulation
exhibited high biocompatibility and was stable for 2 months at room temperature
and for at least 4 months under refrigeration. Taken together, the results
indicate that CAGE is a promising oral delivery vehicle and should be further
explored for oral delivery of insulin and other biologics that are currently
marketed as injectables.
PMID- 29941554
TI - Developmental prosopagnosics have widespread selectivity reductions across
category-selective visual cortex.
AB - Developmental prosopagnosia (DP) is a neurodevelopmental disorder characterized
by severe deficits with facial identity recognition. It is unclear which cortical
areas contribute to face processing deficits in DP, and no previous studies have
investigated whether other category-selective areas function normally in DP. To
address these issues, we scanned 22 DPs and 27 controls using a dynamic localizer
consisting of video clips of faces, scenes, bodies, objects, and scrambled
objects. We then analyzed category selectivity, a measure of the tuning of a
cortical area to a particular visual category. DPs exhibited reduced face
selectivity in all 12 face areas, and the reductions were significant in three
posterior and two anterior areas. DPs and controls showed similar responses to
faces in other category-selective areas, which suggests the DPs' behavioral
deficits with faces result from problems restricted to the face network. DPs also
had pronounced scene-selectivity reductions in four of six scene-selective areas
and marginal body-selectivity reductions in two of four body-selective areas. Our
results demonstrate that DPs have widespread deficits throughout the face
network, and they are inconsistent with a leading account of DP which proposes
that posterior face-selective areas are normal in DP. The selectivity reductions
in other category-selective areas indicate many DPs have deficits spread across
high-level visual cortex.
PMID- 29941555
TI - ZNF281 inhibits neuronal differentiation and is a prognostic marker for
neuroblastoma.
AB - Derangement of cellular differentiation because of mutation or inappropriate
expression of specific genes is a common feature in tumors. Here, we show that
the expression of ZNF281, a zinc finger factor involved in several cellular
processes, decreases during terminal differentiation of murine cortical neurons
and in retinoic acid-induced differentiation of neuroblastoma (NB) cells. The
ectopic expression of ZNF281 inhibits the neuronal differentiation of murine
cortical neurons and NB cells, whereas its silencing causes the opposite effect.
Furthermore, TAp73 inhibits the expression of ZNF281 through miR34a. Conversely,
MYCN promotes the expression of ZNF281 at least in part by inhibiting miR34a.
These findings imply a functional network that includes p73, MYCN, and ZNF281 in
NB cells, where ZNF281 acts by negatively affecting neuronal differentiation.
Array analysis of NB cells silenced for ZNF281 expression identified GDNF and
NRP2 as two transcriptional targets inhibited by ZNF281. Binding of ZNF281 to the
promoters of these genes suggests a direct mechanism of repression. Bioinformatic
analysis of NB datasets indicates that ZNF281 expression is higher in aggressive,
undifferentiated stage 4 than in localized stage 1 tumors supporting a central
role of ZNF281 in affecting the differentiation of NB. Furthermore, patients with
NB with high expression of ZNF281 have a poor clinical outcome compared with low
expressors. These observations suggest that ZNF281 is a controller of neuronal
differentiation that should be evaluated as a prognostic marker in NB.
PMID- 29941556
TI - Changes in brain architecture are consistent with altered fear processing in
domestic rabbits.
AB - The most characteristic feature of domestic animals is their change in behavior
associated with selection for tameness. Here we show, using high-resolution brain
magnetic resonance imaging in wild and domestic rabbits, that domestication
reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting
that areas driving fear have lost volume while areas modulating negative affect
have gained volume during domestication. In contrast to the localized gray matter
alterations, white matter anisotropy was reduced in the corona radiata, corpus
callosum, and the subcortical white matter. This suggests a compromised white
matter structural integrity in projection and association fibers affecting both
afferent and efferent neural flow, consistent with reduced neural processing. We
propose that compared with their wild ancestors, domestic rabbits are less
fearful and have an attenuated flight response because of these changes in brain
architecture.
PMID- 29941557
TI - Focal, remote-controlled, chronic chemical modulation of brain microstructures.
AB - Direct delivery of fluid to brain parenchyma is critical in both research and
clinical settings. This is usually accomplished through acutely inserted
cannulas. This technique, however, results in backflow and significant dispersion
away from the infusion site, offering little spatial or temporal control in
delivering fluid. We present an implantable, MRI-compatible, remotely controlled
drug delivery system for minimally invasive interfacing with brain
microstructures in freely moving animals. We show that infusions through acutely
inserted needles target a region more than twofold larger than that of identical
infusions through chronically implanted probes due to reflux and backflow. We
characterize the dynamics of in vivo infusions using positron emission tomography
techniques. Volumes as small as 167 nL of copper-64 and fludeoxyglucose labeled
agents are quantified. We further demonstrate the importance of precise drug
volume dosing to neural structures to elicit behavioral effects reliably.
Selective modulation of the substantia nigra, a critical node in basal ganglia
circuitry, via muscimol infusion induces behavioral changes in a volume-dependent
manner, even when the total dose remains constant. Chronic device viability is
confirmed up to 1-y implantation in rats. This technology could potentially
enable precise investigation of neurological disease pathology in preclinical
models, and more efficacious treatment in human patients.
PMID- 29941558
TI - Fast charging of lithium-ion batteries at all temperatures.
AB - Fast charging is a key enabler of mainstream adoption of electric vehicles (EVs).
None of today's EVs can withstand fast charging in cold or even cool temperatures
due to the risk of lithium plating. Efforts to enable fast charging are hampered
by the trade-off nature of a lithium-ion battery: Improving low-temperature fast
charging capability usually comes with sacrificing cell durability. Here, we
present a controllable cell structure to break this trade-off and enable lithium
plating-free (LPF) fast charging. Further, the LPF cell gives rise to a unified
charging practice independent of ambient temperature, offering a platform for the
development of battery materials without temperature restrictions. We demonstrate
a 9.5 Ah 170 Wh/kg LPF cell that can be charged to 80% state of charge in 15 min
even at -50 degrees C (beyond cell operation limit). Further, the LPF cell
sustains 4,500 cycles of 3.5-C charging in 0 degrees C with <20% capacity loss,
which is a 90* boost of life compared with a baseline conventional cell, and
equivalent to >12 y and >280,000 miles of EV lifetime under this extreme usage
condition, i.e., 3.5-C or 15-min fast charging at freezing temperatures.
PMID- 29941561
TI - Correction to Supporting Information for Smith et al., Direct measurements of
meltwater runoff on the Greenland ice sheet surface.
PMID- 29941559
TI - Degradation of unmethylated miRNA/miRNA*s by a DEDDy-type 3' to 5'
exoribonuclease Atrimmer 2 in Arabidopsis.
AB - The 3' end methylation catalyzed by HUA Enhancer 1 (HEN1) is a crucial step of
small RNA stabilization in plants, yet how unmethylated small RNAs undergo
degradation remains largely unknown. Using a reverse genetic approach, we here
show that Atrimmer 2 (ATRM2), a DEDDy-type 3' to 5' exoribonuclease, acts in the
degradation of unmethylated miRNAs and miRNA*s in Arabidopsis Loss-of-function
mutations in ATRM2 partially suppress the morphological defects caused by HEN1
malfunction, with restored levels of a subset of miRNAs and receded expression of
corresponding miRNA targets. Dysfunction of ATRM2 has negligible effect on miRNA
trimming, and further increase the fertility of hen1 heso1 urt1, a mutant with an
almost complete abolishment of miRNA uridylation, indicating that ATRM2 may
neither be involved in 3' to 5' trimming nor be the enzyme that specifically
degrades uridylated miRNAs. Notably, the fold changes of miRNAs and their
corresponding miRNA*s were significantly correlated in hen1 atrm2 versus hen1
Unexpectedly, we observed a marked increase of 3' to 5' trimming of several
miRNA*s but not miRNAs in ATRM2 compromised backgrounds. These data suggest an
action of ATRM2 on miRNA/miRNA* duplexes, and the existence of an unknown
exoribonuclease for specific trimming of miRNA*. This asymmetric effect on
miRNA/miRNA* is likely related to Argonaute (AGO) proteins, which can distinguish
miRNAs from miRNA*s. Finally, we show that ATRM2 colocalizes and physically
interacts with Argonaute 1 (AGO1). Taken together, our results suggest that ATRM2
may be involved in the surveillance of unmethylated miRNA/miRNA* duplexes during
the initiation step of RNA-induced silencing complex assembly.
PMID- 29941560
TI - Unusual duplication mutation in a surface loop of human transthyretin leads to an
aggressive drug-resistant amyloid disease.
AB - Transthyretin (TTR) is a globular tetrameric transport protein in plasma. Nearly
140 single amino acid substitutions in TTR cause life-threatening amyloid
disease. We report a one-of-a-kind pathological variant featuring a Glu51, Ser52
duplication mutation (Glu51_Ser52dup). The proband, heterozygous for the
mutation, exhibited an unusually aggressive amyloidosis that was refractory to
treatment with the small-molecule drug diflunisal. To understand the poor
treatment response and expand therapeutic options, we explored the structure and
stability of recombinant Glu51_Ser52dup. The duplication did not alter the
protein secondary or tertiary structure but decreased the stability of the TTR
monomer and tetramer. Diflunisal, which bound with near-micromolar affinity,
partially restored tetramer stability. The duplication had no significant effect
on the free energy and enthalpy of diflunisal binding, and hence on the drug
protein interactions. However, the duplication induced tryptic digestion of TTR
at near-physiological conditions, releasing a C-terminal fragment 49-129 that
formed amyloid fibrils under conditions in which the full-length protein did not.
Such C-terminal fragments, along with the full-length TTR, comprise amyloid
deposits in vivo. Bioinformatics and structural analyses suggested that increased
disorder in the surface loop, which contains the Glu51_Ser52dup duplication, not
only helped generate amyloid-forming fragments but also decreased structural
protection in the amyloidogenic residue segment 25-34, promoting misfolding of
the full-length protein. Our studies of a unique duplication mutation explain its
diflunisal-resistant nature, identify misfolding pathways for amyloidogenic TTR
variants, and provide therapeutic targets to inhibit amyloid fibril formation by
variant TTR.
PMID- 29941563
TI - Computer simulations of Jupiter's deep internal dynamics help interpret what Juno
sees.
AB - We describe computer simulations of thermal convection and magnetic field
generation in Jupiter's deep interior: that is, its convective dynamo. Results
from three different simulations highlight the importance of including the
dynamics in the very deep interior, although much of the convection and field
generation seems to be confined to the upper part of the interior. A long-debated
question is to what depth do Jupiter's zonal winds extend below its surface. Our
simulations suggest that, if global latitudinally banded patterns in Jupiter's
near-surface magnetic and gravity fields were detected by Juno, NASA's orbiting
spacecraft at Jupiter [Bolton S, et al. (2017) Science 356:821-825], they would
provide evidence for Jupiter's zonal winds extending deep below the surface. One
of our simulations has also maintained, for a couple simulated years, a deep
axisymmetric inertial wave, with properties at the surface that depend on the
size of the model's small rocky core. If such a wave was detected on Jupiter's
surface, its latitudes and oscillation frequency would provide evidence for the
existence and size of Jupiter's rocky core.
PMID- 29941562
TI - Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol
secretion in both aggressive and nonaggressive humans.
AB - Violent aggression in humans may involve a modified response to stress, but the
underlying mechanisms are not well understood. Here we show that naturally
present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit
distinct epitope-binding profiles to ACTH peptide in subjects with a history of
violent aggression compared with controls. Namely, while nonaggressive male
controls displayed a preferential IgG binding to the ACTH central part (amino
acids 11-24), subjects who had committed violent acts of aggression had IgG with
increased affinity to ACTH, preferentially binding to its N terminus (amino acids
1-13). Purified IgGs from approximately half of the examined sera were able to
block ACTH-induced cortisol secretion of human adrenal cells in vitro,
irrespective of the source of sample (from a control subject or a violent
aggressor). Nevertheless, in the resident-intruder test in mice, i.p. injection
of residents with ACTH and IgG from aggressive subjects, but not from control
subjects, shortened latency for the first attack against intruders.
Immunohistochemical screening of violent aggressors' sera on rat brain and
pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16
sera revealed selective binding to a nonidentified antigen in vasopressinergic
neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data
show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in
control and violently aggressive subjects. These IgGs can modulate ACTH-induced
cortisol secretion and, hence, are involved in the regulation of the stress
response. However, the possible role of ACTH-reactive autoantibodies in
aggressive behavior needs further investigation.
PMID- 29941564
TI - Phosphatases control PKA-dependent functional microdomains at the outer
mitochondrial membrane.
AB - Evidence supporting the heterogeneity in cAMP and PKA signaling is rapidly
accumulating and has been largely attributed to the localization or activity of
adenylate cyclases, phosphodiesterases, and A-kinase-anchoring proteins in
different cellular subcompartments. However, little attention has been paid to
the possibility that, despite homogeneous cAMP levels, a major heterogeneity in
cAMP/PKA signaling could be generated by the spatial distribution of the final
terminators of this cascade, i.e., the phosphatases. Using FRET-based sensors to
monitor cAMP and PKA-dependent phosphorylation in the cytosol and outer
mitochondrial membrane (OMM) of primary rat cardiomyocytes, we demonstrate that
comparable cAMP increases in these two compartments evoke higher levels of PKA
dependent phosphorylation in the OMM. This difference is most evident for small,
physiological increases of cAMP levels and with both OMM-located probes and
endogenous OMM proteins. We demonstrate that this disparity depends on
differences in the rates of phosphatase-dependent dephosphorylation of PKA
targets in the two compartments. Furthermore, we show that the activity of
soluble phosphatases attenuates PKA-driven activation of the cAMP response
element-binding protein while concurrently enhancing PKA-dependent mitochondrial
elongation. We conclude that phosphatases can sculpt functionally distinct
cAMP/PKA domains even in the absence of gradients or microdomains of this
messenger. We present a model that accounts for these unexpected results in which
the degree of PKA-dependent phosphorylation is dictated by both the subcellular
distribution of the phosphatases and the different accessibility of membrane
bound and soluble phosphorylated substrates to the cytosolic enzymes.
PMID- 29941566
TI - Correction for Fustin et al., Two Ck1delta transcripts regulated by m6A
methylation code for two antagonistic kinases in the control of the circadian
clock.
PMID- 29941567
TI - Disease outbreak thresholds emerge from interactions between movement behavior,
landscape structure, and epidemiology.
AB - Disease models have provided conflicting evidence as to whether spatial
heterogeneity promotes or impedes pathogen persistence. Moreover, there has been
limited theoretical investigation into how animal movement behavior interacts
with the spatial organization of resources (e.g., clustered, random, uniform)
across a landscape to affect infectious disease dynamics. Importantly, spatial
heterogeneity of resources can sometimes lead to nonlinear or counterintuitive
outcomes depending on the host and pathogen system. There is a clear need to
develop a general theoretical framework that could be used to create testable
predictions for specific host-pathogen systems. Here, we develop an individual
based model integrated with movement ecology approaches to investigate how host
movement behaviors interact with landscape heterogeneity (in the form of various
levels of resource abundance and clustering) to affect pathogen dynamics. For
most of the parameter space, our results support the counterintuitive idea that
fragmentation promotes pathogen persistence, but this finding was largely
dependent on perceptual range of the host, conspecific density, and recovery
rate. For simulations with high conspecific density, slower recovery rates, and
larger perceptual ranges, more complex disease dynamics emerged, and the most
fragmented landscapes were not necessarily the most conducive to outbreaks or
pathogen persistence. These results point to the importance of interactions
between landscape structure, individual movement behavior, and pathogen
transmission for predicting and understanding disease dynamics.
PMID- 29941565
TI - Staphylococcus aureus biofilms release leukocidins to elicit extracellular trap
formation and evade neutrophil-mediated killing.
AB - Bacterial biofilms efficiently evade immune defenses, greatly complicating the
prognosis of chronic infections. How methicillin-resistant Staphylococcus aureus
(MRSA) biofilms evade host immune defenses is largely unknown. This study
describes some of the major mechanisms required for S. aureus biofilms to evade
the innate immune response and provides evidence of key virulence factors
required for survival and persistence of bacteria during chronic infections.
Neutrophils are the most abundant white blood cells in circulation, playing
crucial roles in the control and elimination of bacterial pathogens.
Specifically, here we show that, unlike single-celled populations, S. aureus
biofilms rapidly skew neutrophils toward neutrophil extracellular trap (NET)
formation through the combined activity of leukocidins Panton-Valentine
leukocidin and gamma-hemolysin AB. By eliciting this response, S. aureus was able
to persist, as the antimicrobial activity of released NETs was ineffective at
clearing biofilm bacteria. Indeed, these studies suggest that NETs could
inadvertently potentiate biofilm infections. Last, chronic infection in a porcine
burn wound model clearly demonstrated that leukocidins are required for "NETosis"
and facilitate bacterial survival in vivo.
PMID- 29941568
TI - Vibrational coherence transfer in the ultrafast intersystem crossing of a
diplatinum complex in solution.
AB - We investigate the ultrafast transient absorption response of tetrakis(MU
pyrophosphito)diplatinate(II), [Pt2(MU-P2O5H2)4]4- [hereafter abbreviated
Pt(pop)], in acetonitrile upon excitation of its lowest singlet 1A2u state.
Compared with previously reported solvents [van der Veen RM, Cannizzo A, van
Mourik F, Vlcek A, Jr, Chergui M (2011) J Am Chem Soc 133:305-315], a significant
shortening of the intersystem crossing (ISC) time (<1 ps) from the lowest singlet
to the lowest triplet state is found, allowing for a transfer of vibrational
coherence, observed in the course of an ISC in a polyatomic molecule in solution.
Density functional theory (DFT) quantum mechanical/molecular mechanical (QM/MM)
simulations of Pt(pop) in acetonitrile and ethanol show that high-lying, mostly
triplet, states are strongly mixed and shifted to lower energies due to
interactions with the solvent, providing an intermediate state (or manifold of
states) for the ISC. This suggests that the larger the solvation energies of the
intermediate state(s), the shorter the ISC time. Because the latter is smaller
than the pure dephasing time of the vibrational wave packet, coherence is
conserved during the spin transition. These results underscore the crucial role
of the solvent in directing pathways of intramolecular energy flow.
PMID- 29941569
TI - Ionophoric effects of the antitubercular drug bedaquiline.
AB - Bedaquiline (BDQ), an inhibitor of the mycobacterial F1Fo-ATP synthase, has
revolutionized the antitubercular drug discovery program by defining energy
metabolism as a potent new target space. Several studies have recently suggested
that BDQ ultimately causes mycobacterial cell death through a phenomenon known as
uncoupling. The biochemical basis underlying this, in BDQ, is unresolved and may
represent a new pathway to the development of effective therapeutics. In this
communication, we demonstrate that BDQ can inhibit ATP synthesis in Escherichia
coli by functioning as a H+/K+ ionophore, causing transmembrane pH and potassium
gradients to be equilibrated. Despite the apparent lack of a BDQ-binding site,
incorporating the E. coli Fo subunit into liposomes enhanced the ionophoric
activity of BDQ. We discuss the possibility that localization of BDQ at F1Fo-ATP
synthases enables BDQ to create an uncoupled microenvironment, by antiporting
H+/K+ Ionophoric properties may be desirable in high-affinity antimicrobials
targeting integral membrane proteins.
PMID- 29941570
TI - Costs, needs, and integration efforts shape helping behavior toward refugees.
AB - Recent political instabilities and conflicts around the world have drastically
increased the number of people seeking refuge. The challenges associated with the
large number of arriving refugees have revealed a deep divide among the citizens
of host countries: one group welcomes refugees, whereas another rejects them. Our
research aim is to identify factors that help us understand host citizens'
(un)willingness to help refugees. We devise an economic game that captures the
basic structural properties of the refugee situation. We use it to investigate
both economic and psychological determinants of citizens' prosocial behavior
toward refugees. In three controlled laboratory studies, we find that helping
refugees becomes less likely when it is individually costly to the citizens. At
the same time, helping becomes more likely with the refugees' neediness: helping
increases when it prevents a loss rather than generates a gain for the refugees.
Moreover, particularly citizens with higher degrees of prosocial orientation are
willing to provide help at a personal cost. When refugees have to exert a minimum
level of effort to be eligible for support by the citizens, these mandatory
"integration efforts" further increase prosocial citizens' willingness to help.
Our results underscore that economic factors play a key role in shaping
individual refugee helping behavior but also show that psychological factors
modulate how individuals respond to them. Moreover, our economic game is a useful
complement to correlational survey measures and can be used for pretesting policy
measures aimed at promoting prosocial behavior toward refugees.
PMID- 29941571
TI - Interplay of a secreted protein with type IVb pilus for efficient enterotoxigenic
Escherichia coli colonization.
AB - Initial attachment and subsequent colonization of the intestinal epithelium
comprise critical events allowing enteric pathogens to survive and express their
pathogenesis. In enterotoxigenic Escherichia coli (ETEC), these are mediated by a
long proteinaceous fiber termed type IVb pilus (T4bP). We have reported that the
colonization factor antigen/III (CFA/III), an operon-encoded T4bP of ETEC,
possesses a minor pilin, CofB, that carries an H-type lectin domain at its tip.
Although CofB is critical for pilus assembly by forming a trimeric initiator
complex, its importance for bacterial attachment remains undefined. Here, we show
that T4bP is not sufficient for bacterial attachment, which also requires a
secreted protein CofJ, encoded within the same CFA/III operon. The crystal
structure of CofB complexed with a peptide encompassing the binding region of
CofJ showed that CofJ interacts with CofB by anchoring its flexible N-terminal
extension to be embedded deeply into the expected carbohydrate recognition site
of the CofB H-type lectin domain. By combining this structure and physicochemical
data in solution, we built a plausible model of the CofJ-CFA/III pilus complex,
which suggested that CofJ acts as a molecular bridge by binding both T4bP and the
host cell membrane. The Fab fragments of a polyclonal antibody against CofJ
significantly inhibited bacterial attachment by preventing the adherence of
secreted CofJ proteins. These findings signify the interplay between T4bP and a
secreted protein for attaching to and colonizing the host cell surface,
potentially constituting a therapeutic target against ETEC infection.
PMID- 29941572
TI - How gender determines the way we speak about professionals.
AB - Gender inequality persists in many professions, particularly in high-status
fields, such as science, technology, engineering, and math. We report evidence of
a form of gender bias that may contribute to this state: gender influences the
way that people speak about professionals. When discussing professionals or their
work, it is common to refer to them by surname alone (e.g., "Darwin developed the
theory of evolution"). We present evidence that people are more likely to refer
to male than female professionals in this way. This gender bias emerges in
archival data across domains; students reviewing professors online and pundits
discussing politicians on the radio are more likely to use surname when speaking
about a man (vs. a woman). Participants' self-reported references also indicate a
preference for using surname when speaking about male (vs. female) scientists,
authors, and others. Finally, experimental evidence provides convergent evidence:
participants writing about a fictional male scientist are more likely to refer to
him by surname than participants writing about an otherwise identical female
scientist. We find that, on average, people are over twice as likely to refer to
male professionals by surname than female professionals. Critically, we
identified consequences of this gender bias in speaking about professionals.
Researchers referred to by surname are judged as more famous and eminent. They
are consequently seen as higher status and more deserving of eminence-related
benefits and awards. For instance, scientists referred to by surname were seen as
14% more deserving of a National Science Foundation career award.
PMID- 29941573
TI - Kinetics teach that electronic coupling lowers the free-energy change that
accompanies electron transfer.
AB - Electron-transfer theories predict that an increase in the quantum-mechanical
mixing (HDA) of electron donor and acceptor wavefunctions at the instant of
electron transfer drives equilibrium constants toward unity. Kinetic and
equilibrium studies of four acceptor-bridge-donor (A-B-D) compounds reported
herein provide experimental validation of this prediction. The compounds have two
redox-active groups that differ only by the orientation of the aromatic bridge: a
phenyl-thiophene bridge (p) that supports strong electronic coupling of HDA >
1,000 cm-1; and a xylyl-thiophene bridge (x) that prevents planarization and
decreases HDA < 100 cm-1 without a significant change in distance. Pulsed-light
excitation allowed kinetic determination of the equilibrium constant, Keq In
agreement with theory, Keq(p) were closer to unity compared to Keq(x). A van't
Hoff analysis provided clear evidence of an adiabatic electron-transfer pathway
for p-series and a nonadiabatic pathway for x-series. Collectively, the data show
that the absolute magnitude of the thermodynamic driving force for electron
transfers are decreased when adiabatic pathways are operative, a finding that
should be taken into account in the design of hybrid materials for solar energy
conversion.
PMID- 29941574
TI - Correction for Artemenko et al., Chemical and mechanical stimuli act on common
signal transduction and cytoskeletal networks.
PMID- 29941575
TI - Correction for Mandal et al., Mapping intracellular mechanics on micropatterned
substrates.
PMID- 29941576
TI - Coupled laboratory and field investigations resolve microbial interactions that
underpin persistence in hydraulically fractured shales.
AB - Hydraulic fracturing is one of the industrial processes behind the surging
natural gas output in the United States. This technology inadvertently creates an
engineered microbial ecosystem thousands of meters below Earth's surface. Here,
we used laboratory reactors to perform manipulations of persisting shale
microbial communities that are currently not feasible in field scenarios.
Metaproteomic and metabolite findings from the laboratory were then corroborated
using regression-based modeling performed on metagenomic and metabolite data from
more than 40 produced fluids from five hydraulically fractured shale wells.
Collectively, our findings show that Halanaerobium, Geotoga, and
Methanohalophilus strain abundances predict a significant fraction of nitrogen
and carbon metabolites in the field. Our laboratory findings also exposed cryptic
predatory, cooperative, and competitive interactions that impact microorganisms
across fractured shales. Scaling these results from the laboratory to the field
identified mechanisms underpinning biogeochemical reactions, yielding knowledge
that can be harnessed to potentially increase energy yields and inform management
practices in hydraulically fractured shales.
PMID- 29941577
TI - Piano training enhances the neural processing of pitch and improves speech
perception in Mandarin-speaking children.
AB - Musical training confers advantages in speech-sound processing, which could play
an important role in early childhood education. To understand the mechanisms of
this effect, we used event-related potential and behavioral measures in a
longitudinal design. Seventy-four Mandarin-speaking children aged 4-5 y old were
pseudorandomly assigned to piano training, reading training, or a no-contact
control group. Six months of piano training improved behavioral auditory word
discrimination in general as well as word discrimination based on vowels compared
with the controls. The reading group yielded similar trends. However, the piano
group demonstrated unique advantages over the reading and control groups in
consonant-based word discrimination and in enhanced positive mismatch responses
(pMMRs) to lexical tone and musical pitch changes. The improved word
discrimination based on consonants correlated with the enhancements in musical
pitch pMMRs among the children in the piano group. In contrast, all three groups
improved equally on general cognitive measures, including tests of IQ, working
memory, and attention. The results suggest strengthened common sound processing
across domains as an important mechanism underlying the benefits of musical
training on language processing. In addition, although we failed to find far
transfer effects of musical training to general cognition, the near-transfer
effects to speech perception establish the potential for musical training to help
children improve their language skills. Piano training was not inferior to
reading training on direct tests of language function, and it even seemed
superior to reading training in enhancing consonant discrimination.
PMID- 29941578
TI - Tandem internal models execute motor learning in the cerebellum.
AB - In performing skillful movement, humans use predictions from internal models
formed by repetition learning. However, the computational organization of
internal models in the brain remains unknown. Here, we demonstrate that a
computational architecture employing a tandem configuration of forward and
inverse internal models enables efficient motor learning in the cerebellum. The
model predicted learning adaptations observed in hand-reaching experiments in
humans wearing a prism lens and explained the kinetic components of these
behavioral adaptations. The tandem system also predicted a form of subliminal
motor learning that was experimentally validated after training intentional
misses of hand targets. Patients with cerebellar degeneration disease showed
behavioral impairments consistent with tandemly arranged internal models. These
findings validate computational tandemization of internal models in motor control
and its potential uses in more complex forms of learning and cognition.
PMID- 29941579
TI - The mutagen and carcinogen cadmium is a high-affinity inhibitor of the zinc
dependent MutLalpha endonuclease.
AB - MutLalpha (MLH1-PMS2 heterodimer), which acts as a strand-directed endonuclease
during the initiation of eukaryotic mismatch repair, has been postulated to
function as a zinc-dependent enzyme [Kosinski J, Plotz G, Guarne A, Bujnicki JM,
Friedhoff P (2008) J Mol Biol 382:610-627]. We show that human MutLalpha
copurifies with two bound zinc ions, at least one of which resides within the
endonuclease active site, and that bound zinc is required for endonuclease
function. Mutagenic action of the carcinogen cadmium, a known inhibitor of zinc
dependent enzymes, is largely due to selective inhibition of mismatch repair [Jin
YH, et al. (2003) Nat Genet 34:326-329]. We show that cadmium is a potent
inhibitor (apparent Ki ~ 200 nM) of MutLalpha endonuclease and that cadmium
inhibition is reversed by zinc. We also show that inhibition of mismatch repair
in cadmium-treated nuclear extract is significantly reversed by exogenous
MutLalpha but not by MutSalpha (MSH2-MSH6 heterodimer) and that MutLalpha
reversal depends on integrity of the endonuclease active site. Exogenous
MutLalpha also partially rescues the mismatch repair defect in nuclear extract
prepared from cells exposed to cadmium. These findings indicate that targeted
inhibition of MutLalpha endonuclease contributes to cadmium inhibition of
mismatch repair. This effect may play a role in the mechanism of cadmium
carcinogenesis.
PMID- 29941582
TI - QnAs with Gary A. Glatzmaier.
PMID- 29941580
TI - Reversible inhibition of the ClpP protease via an N-terminal conformational
switch.
AB - Protein homeostasis is critically important for cell viability. Key to this
process is the refolding of misfolded or aggregated proteins by molecular
chaperones or, alternatively, their degradation by proteases. In most prokaryotes
and in chloroplasts and mitochondria, protein degradation is performed by the
caseinolytic protease ClpP, a tetradecamer barrel-like proteolytic complex.
Dysregulating ClpP function has shown promise in fighting antibiotic resistance
and as a potential therapy for acute myeloid leukemia. Here we use methyl
transverse relaxation-optimized spectroscopy (TROSY)-based NMR, cryo-EM,
biochemical assays, and molecular dynamics simulations to characterize the
structural dynamics of ClpP from Staphylococcus aureus (SaClpP) in wild-type and
mutant forms in an effort to discover conformational hotspots that regulate its
function. Wild-type SaClpP was found exclusively in the active extended form,
with the N-terminal domains of its component protomers in predominantly beta
hairpin conformations that are less well-defined than other regions of the
protein. A hydrophobic site was identified that, upon mutation, leads to
unfolding of the N-terminal domains, loss of SaClpP activity, and formation of a
previously unobserved split-ring conformation with a pair of 20-A-wide pores in
the side of the complex. The extended form of the structure and partial activity
can be restored via binding of ADEP small-molecule activators. The observed
structural plasticity of the N-terminal gates is shown to be a conserved feature
through studies of Escherichia coli and Neisseria meningitidis ClpP, suggesting a
potential avenue for the development of molecules to allosterically modulate the
function of ClpP.
PMID- 29941581
TI - In vivo imaging of the pathophysiological changes and neutrophil dynamics in
influenza virus-infected mouse lungs.
AB - The pathophysiological changes that occur in lungs infected with influenza
viruses are poorly understood. Here we established an in vivo imaging system that
combines two-photon excitation microscopy and fluorescent influenza viruses of
different pathogenicity. This approach allowed us to monitor and correlate
several parameters and physiological changes including the spread of infection,
pulmonary permeability, pulmonary perfusion speed, number of recruited
neutrophils in infected lungs, and neutrophil motion in the lungs of live mice.
Several physiological changes were larger and occurred earlier in mice infected
with a highly pathogenic H5N1 influenza virus compared with those infected with a
mouse-adapted human strain. These findings demonstrate the potential of our in
vivo imaging system to provide novel information about the pathophysiological
consequences of virus infections.
PMID- 29941583
TI - Correction for Smith et al., Myosin IIA interacts with the spectrin-actin
membrane skeleton to control red blood cell membrane curvature and deformability.
PMID- 29941586
TI - Correction for Lampert et al., Shear force-based genetic screen reveals negative
regulators of cell adhesion and protrusive activity.
PMID- 29941584
TI - Real-time dynamics of mutagenesis reveal the chronology of DNA repair and damage
tolerance responses in single cells.
AB - Evolutionary processes are driven by diverse molecular mechanisms that act in the
creation and prevention of mutations. It remains unclear how these mechanisms are
regulated because limitations of existing mutation assays have precluded
measuring how mutation rates vary over time in single cells. Toward this goal, I
detected nascent DNA mismatches as a proxy for mutagenesis and simultaneously
followed gene expression dynamics in single Escherichia coli cells using
microfluidics. This general microscopy-based approach revealed the real-time
dynamics of mutagenesis in response to DNA alkylation damage and antibiotic
treatments. It also enabled relating the creation of DNA mismatches to the
chronology of the underlying molecular processes. By avoiding population
averaging, I discovered cell-to-cell variation in mutagenesis that correlated
with heterogeneity in the expression of alternative responses to DNA damage.
Pulses of mutagenesis are shown to arise from transient DNA repair deficiency.
Constitutive expression of DNA repair pathways and induction of damage tolerance
by the SOS response compensate for delays in the activation of inducible DNA
repair mechanisms, together providing robustness against the toxic and mutagenic
effects of DNA alkylation damage.
PMID- 29941585
TI - Structure of RNA polymerase complex and genome within a dsRNA virus provides
insights into the mechanisms of transcription and assembly.
AB - Most double-stranded RNA (dsRNA) viruses transcribe RNA plus strands within a
common innermost capsid shell. This process requires coordinated efforts by RNA
dependent RNA polymerase (RdRp) together with other capsid proteins and genomic
RNA. Here we report the near-atomic resolution structure of the RdRp protein VP2
in complex with its cofactor protein VP4 and genomic RNA within an aquareovirus
capsid using 200-kV cryoelectron microscopy and symmetry-mismatch reconstruction.
The structure of these capsid proteins enabled us to observe the elaborate
nonicosahedral structure within the double-layered icosahedral capsid. Our
structure shows that the RdRp complex is anchored at the inner surface of the
capsid shell and interacts with genomic dsRNA and four of the five asymmetrically
arranged N termini of the capsid shell proteins under the fivefold axis, implying
roles for these N termini in virus assembly. The binding site of the RNA end at
VP2 is different from the RNA cap binding site identified in the crystal
structure of orthoreovirus RdRp lambda3, although the structures of VP2 and
lambda3 are almost identical. A loop, which was thought to separate the RNA
template and transcript, interacts with an apical domain of the capsid shell
protein, suggesting a mechanism for regulating RdRp replication and
transcription. A conserved nucleoside triphosphate binding site was localized in
our RdRp cofactor protein VP4 structure, and interactions between the VP4 and the
genomic RNA were identified.
PMID- 29941588
TI - Correction to Supporting Information for Rashidian et al., Noninvasive imaging of
immune responses.
PMID- 29941587
TI - F-actin homeostasis through transcriptional regulation and proteasome-mediated
proteolysis.
AB - Many organisms possess multiple and often divergent actins whose regulation and
roles are not understood in detail. For example, Chlamydomonas reinhardtii has
both a conventional actin (IDA5) and a highly divergent one (NAP1); only IDA5 is
expressed in normal proliferating cells. We showed previously that the drug
latrunculin B (LatB) causes loss of filamentous (F-) IDA5 and strong up
regulation of NAP1, which then provides essential actin function(s) by forming
LatB-resistant F-NAP1. RNA-sequencing analyses now show that this up-regulation
of NAP1 reflects a broad transcriptional response, much of which depends on three
proteins (LAT1, LAT2, and LAT3) identified previously as essential for NAP1
transcription. Many of the LAT-regulated genes contain a putative cis-acting
regulatory site, the "LRE motif." The LatB transcriptional program appears to be
activated by loss of F-IDA5 and deactivated by formation of F-NAP1, thus forming
an F-actin-dependent negative-feedback loop. Multiple genes encoding proteins of
the ubiquitin-proteasome system are among those induced by LatB, resulting in
rapid degradation of IDA5 (but not NAP1). Our results suggest that IDA5
degradation is functionally important because nonpolymerizable LatB-bound IDA5
interferes with the formation of F-NAP1. The genes for the actin-interacting
proteins cofilin and profilin are also induced. Cofilin induction may further the
clearance of IDA5 by promoting the scission of F-IDA5, whereas profilin appears
to function in protecting monomeric IDA5 from degradation. This multifaceted
regulatory system allows rapid and quantitative turnover of F-actin in response
to cytoskeletal perturbations and probably also maintains F-actin homeostasis
under normal growth conditions.
PMID- 29941589
TI - Structure of the Lassa virus glycan shield provides a model for immunological
resistance.
AB - Lassa virus is an Old World arenavirus endemic to West Africa that causes severe
hemorrhagic fever. Vaccine development has focused on the envelope glycoprotein
complex (GPC) that extends from the virion envelope. The often inadequate
antibody immune response elicited by both vaccine and natural infection has been,
in part, attributed to the abundance of N-linked glycosylation on the GPC. Here,
using a virus-like-particle system that presents Lassa virus GPC in a native-like
context, we determine the composite population of each of the N-linked
glycosylation sites presented on the trimeric GPC spike. Our analysis reveals the
presence of underprocessed oligomannose-type glycans, which form punctuated
clusters that obscure the proteinous surface of both the GP1 attachment and GP2
fusion glycoprotein subunits of the Lassa virus GPC. These oligomannose clusters
are seemingly derived as a result of sterically reduced accessibility to glycan
processing enzymes, and limited amino acid diversification around these sites
supports their role protecting against the humoral immune response. Combined, our
data provide a structure-based blueprint for understanding how glycans render the
glycoprotein spikes of Lassa virus and other Old World arenaviruses
immunologically resistant targets.
PMID- 29941591
TI - Multigenome analysis implicates miniature inverted-repeat transposable elements
(MITEs) in metabolic diversification in eudicots.
AB - Plants produce a plethora of natural products, including many drugs. It has
recently emerged that the genes encoding different natural product pathways may
be organized as biosynthetic gene clusters in plant genomes, with >30 examples
reported so far. Despite superficial similarities with microbes, these clusters
have not arisen by horizontal gene transfer, but rather by gene duplication,
neofunctionalization, and relocation via unknown mechanisms. Previously we
reported that two Arabidopsis thaliana biosynthetic gene clusters are located in
regions of the genome that are significantly enriched in transposable elements
(TEs). Other plant biosynthetic gene clusters also harbor abundant TEs. TEs can
mediate genomic rearrangement by providing homologous sequences that enable
illegitimate recombination and gene relocation. Thus, TE-mediated recombination
may contribute to plant biosynthetic gene cluster formation. TEs may also
facilitate establishment of regulons. However, a systematic analysis of the TEs
associated with plant biosynthetic gene clusters has not been carried out. Here
we investigate the TEs associated with clustered terpene biosynthetic genes in
multiple plant genomes and find evidence to suggest a role for miniature inverted
repeat transposable elements in cluster formation in eudicots. Through
investigation of the newly sequenced Amborella trichopoda, Aquilegia coerulea,
and Kalanchoe fedtschenkoi genomes, we further show that the "block" mechanism of
founding of biosynthetic gene clusters through duplication and diversification of
pairs of terpene synthase and cytochrome P450 genes that is prevalent in the
eudicots arose around 90-130 million years ago, after the appearance of the basal
eudicots and before the emergence of the superrosid clade.
PMID- 29941590
TI - Inhibitor of intramembrane protease RseP blocks the sigmaE response causing
lethal accumulation of unfolded outer membrane proteins.
AB - The outer membrane (OM) of Gram-negative bacteria forms a robust permeability
barrier that blocks entry of toxins and antibiotics. Most OM proteins (OMPs)
assume a beta-barrel fold, and some form aqueous channels for nutrient uptake and
efflux of intracellular toxins. The Bam machine catalyzes rapid folding and
assembly of OMPs. Fidelity of OMP biogenesis is monitored by the sigmaE stress
response. When OMP folding defects arise, the proteases DegS and RseP act
sequentially to liberate sigmaE into the cytosol, enabling it to activate
transcription of the stress regulon. Here, we identify batimastat as a selective
inhibitor of RseP that causes a lethal decrease in sigmaE activity in Escherichia
coli, and we further identify RseP mutants that are insensitive to inhibition and
confer resistance. Remarkably, batimastat treatment allows the capture of elusive
intermediates in the OMP biogenesis pathway and offers opportunities to better
understand the underlying basis for sigmaE essentiality.
PMID- 29941592
TI - Fisheries bycatch risk to marine megafauna is intensified in Lagrangian coherent
structures.
AB - Incidental catch of nontarget species (bycatch) is a major barrier to ecological
and economic sustainability in marine capture fisheries. Key to mitigating
bycatch is an understanding of the habitat requirements of target and nontarget
species and the influence of heterogeneity and variability in the dynamic marine
environment. While patterns of overlap among marine capture fisheries and
habitats of a taxonomically diverse range of marine vertebrates have been
reported, a mechanistic understanding of the real-time physical drivers of
bycatch events is lacking. Moving from describing patterns toward understanding
processes, we apply a Lagrangian analysis to a high-resolution ocean model output
to elucidate the fundamental mechanisms that drive fisheries interactions. We
find that the likelihood of marine megafauna bycatch is intensified in attracting
Lagrangian coherent structures associated with submesoscale and mesoscale
filaments, fronts, and eddies. These results highlight how the real-time tracking
of dynamic structures in the oceans can support fisheries sustainability and
advance ecosystem-based management.
PMID- 29941593
TI - Enhancement of Ebola virus infection by seminal amyloid fibrils.
AB - The 2014 western Africa Ebola virus (EBOV) epidemic was unprecedented in
magnitude, infecting over 28,000 and causing over 11,000 deaths. During this
outbreak, multiple instances of EBOV sexual transmission were reported, including
cases where the infectious individual had recovered from EBOV disease months
before transmission. Potential human host factors in EBOV sexual transmission
remain unstudied. Several basic seminal amyloids, most notably semen-derived
enhancer of viral infection (SEVI), enhance in vitro infection by HIV and several
other viruses. To test the ability of these peptides to enhance EBOV infection,
viruses bearing the EBOV glycoprotein (EboGP) were preincubated with
physiological concentrations of SEVI before infection of physiologically relevant
cell lines and primary cells. Preincubation with SEVI significantly increased
EboGP-mediated infectivity and replication in epithelium- and monocyte-derived
cell lines. This enhancement was dependent upon amyloidogenesis and positive
charge, and infection results were observed with both viruses carrying EboGP and
authentic EBOV as well as with semen. SEVI enhanced binding of virus to cells and
markedly increased its subsequent internalization. SEVI also stimulated uptake of
a fluid phase marker by macropinocytosis, a critical mechanism by which cells
internalize EBOV. We report a previously unrecognized ability of SEVI and semen
to significantly alter viral physical properties critical for transmissibility by
increasing the stability of EboGP-bearing recombinant viruses during incubation
at elevated temperature and providing resistance to desiccation. Given the
potential for EBOV sexual transmission to spark new transmission chains, these
findings represent an important interrogation of factors potentially important
for this EBOV transmission route.
PMID- 29941594
TI - Formation of HONO from the NH3-promoted hydrolysis of NO2 dimers in the
atmosphere.
AB - One challenging issue in atmospheric chemistry is identifying the source of
nitrous acid (HONO), which is believed to be a primary source of atmospheric
"detergent" OH radicals. Herein, we show a reaction route for the formation of
HONO species from the NH3-promoted hydrolysis of a NO2 dimer (ONONO2), which
entails a low free-energy barrier of 0.5 kcal/mol at room temperature. Our
systematic study of HONO formation based on NH3 + ONONO2 + nH2O and water droplet
systems with the metadynamics simulation method and a reaction pathway searching
method reveals two distinct mechanisms: (i) In monohydrates (n = 1),
tetrahydrates (n = 4), and water droplets, only one water molecule is directly
involved in the reaction (denoted the single-water mechanism); and (ii) the
splitting of two neighboring water molecules is seen in the dihydrates (n = 2)
and trihydrates (n = 3) (denoted the dual-water mechanism). A comparison of the
computed free-energy surface for NH3-free and NH3-containing systems indicates
that gaseous NH3 can markedly lower the free-energy barrier to HONO formation
while stabilizing the product state, producing a more exergonic reaction, in
contrast to the endergonic reaction for the NH3-free system. More importantly,
the water droplet reduces the free-energy barrier for HONO formation to 0.5
kcal/mol, which is negligible at room temperature. We show that the entropic
contribution is important in the mechanism by which NH3 promotes HONO formation.
This study provides insight into the importance of fundamental HONO chemistry and
its broader implication to aerosol and cloud processing chemistry at the air
water interface.
PMID- 29941595
TI - Near-optimal matrix recovery from random linear measurements.
AB - In matrix recovery from random linear measurements, one is interested in
recovering an unknown M-by-N matrix [Formula: see text] from [Formula: see text]
measurements [Formula: see text], where each [Formula: see text] is an M-by-N
measurement matrix with i.i.d. random entries, [Formula: see text] We present a
matrix recovery algorithm, based on approximate message passing, which
iteratively applies an optimal singular-value shrinker-a nonconvex nonlinearity
tailored specifically for matrix estimation. Our algorithm typically converges
exponentially fast, offering a significant speedup over previously suggested
matrix recovery algorithms, such as iterative solvers for nuclear norm
minimization (NNM). It is well known that there is a recovery tradeoff between
the information content of the object [Formula: see text] to be recovered
(specifically, its matrix rank r) and the number of linear measurements n from
which recovery is to be attempted. The precise tradeoff between r and n, beyond
which recovery by a given algorithm becomes possible, traces the so-called phase
transition curve of that algorithm in the [Formula: see text] plane. The phase
transition curve of our algorithm is noticeably better than that of NNM.
Interestingly, it is close to the information-theoretic lower bound for the
minimal number of measurements needed for matrix recovery, making it not only
state of the art in terms of convergence rate, but also near optimal in terms of
the matrices it successfully recovers.
PMID- 29941596
TI - Mouse maternal protein restriction during preimplantation alone permanently
alters brain neuron proportion and adult short-term memory.
AB - Maternal protein malnutrition throughout pregnancy and lactation compromises
brain development in late gestation and after birth, affecting structural,
biochemical, and pathway dynamics with lasting consequences for motor and
cognitive function. However, the importance of nutrition during the
preimplantation period for brain development is unknown. We have previously shown
that maternal low-protein diet (LPD) confined to the preimplantation period (Emb
LPD) in mice, with normal nutrition thereafter, is sufficient to induce
cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here,
using a range of in vivo and in vitro techniques, we report that Emb-LPD and
sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5,
E14.5, and E17.5 through suppressed proliferation rates in both ganglionic
eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs
to up-regulate the neuronal differentiation rate beyond control levels, whereas
in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb
LPD adult offspring maintain the increase in neuron proportion in the cortex,
display increased cortex thickness, and exhibit short-term memory deficit
analyzed by the novel-object recognition assay. Last, we identify altered
expression of fragile X family genes as a potential molecular mechanism for
adverse programming of brain development. Collectively, these data demonstrate
that poor maternal nutrition from conception is sufficient to cause abnormal
brain development and adult memory loss.
PMID- 29941597
TI - Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via
interaction with VAPA and VAPB.
AB - Kv2.1 exhibits two distinct forms of localization patterns on the neuronal plasma
membrane: One population is freely diffusive and regulates electrical activity
via voltage-dependent K+ conductance while a second one localizes to micrometer
sized clusters that contain densely packed, but nonconducting, channels. We have
previously established that these clusters represent endoplasmic reticulum/plasma
membrane (ER/PM) junctions that function as membrane trafficking hubs and that
Kv2.1 plays a structural role in forming these membrane contact sites in both
primary neuronal cultures and transfected HEK cells. Clustering and the formation
of ER/PM contacts are regulated by phosphorylation within the channel C terminus,
offering cells fast, dynamic control over the physical relationship between the
cortical ER and PM. The present study addresses the mechanisms by which Kv2.1 and
the related Kv2.2 channel interact with the ER membrane. Using proximity-based
biotinylation techniques in transfected HEK cells we identified ER VAMP
associated proteins (VAPs) as potential Kv2.1 interactors. Confirmation that
Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA
knockdown, and Forster resonance energy transfer (FRET)-based assays. CD4
chimeras containing sequence from the Kv2.1 C terminus were used to identify a
noncanonical VAP-binding motif. VAPs were first identified as proteins required
for neurotransmitter release in Aplysia and are now known to be abundant
scaffolding proteins involved in membrane contact site formation throughout the
ER. The VAP interactome includes AKAPs, kinases, membrane trafficking machinery,
and proteins regulating nonvesicular lipid transport from the ER to the PM.
Therefore, the Kv2-induced VAP concentration at ER/PM contact sites is predicted
to have wide-ranging effects on neuronal cell biology.
PMID- 29941598
TI - Direct cell-cell contact activates SigM to express the ESX-4 secretion system in
Mycobacterium smegmatis.
AB - Conjugal cell-cell contact between strains of Mycobacterium smegmatis induces the
esxUT transcript, which encodes the putative primary substrates of the ESAT-6
secretion system 4 (ESX-4) secretion system. This recipient response was required
for conjugal transfer of chromosomal DNA from the donor strain. Here we show that
the extracytoplasmic sigma factor, SigM, is a cell contact-dependent activator of
ESX-4 expression and is required for conjugal transfer of DNA in the recipient
strain. The SigM regulon includes genes outside the seven-gene core esx4 locus
that we show are also required for conjugation, and we show that some of these
SigM-induced proteins likely function through ESX-4. A fluorescent reporter
revealed that SigM is specifically activated in recipient cells in direct contact
with donor cells. Coculture RNA-seq experiments indicated that SigM regulon
induction occurred early and before transconjugants are detected. This work
supports a model wherein donor contact with the recipient cell surface
inactivates the transmembrane anti-SigM, thereby releasing SigM. Free SigM
induces an extended ESX-4 secretion system, resulting in changes that facilitate
chromosomal transfer. The contact-dependent inactivation of an extracytoplasmic
sigma-factor that tightly controls ESX-4 activity suggests a mechanism dedicated
to detect, and appropriately respond to, external stimuli from mycobacteria.
PMID- 29941599
TI - O-GlcNAcylation regulates the stability and enzymatic activity of the histone
methyltransferase EZH2.
AB - Protein O-glycosylation by attachment of beta-N-acetylglucosamine (GlcNAc) to the
Ser or Thr residue is a major posttranslational glycosylation event and is often
associated with protein folding, stability, and activity. The methylation of
histone H3 at Lys-27 catalyzed by the methyltransferase EZH2 was known to
suppress gene expression and cancer development, and we previously reported that
the O-GlcNAcylation of EZH2 at S76 stabilized EZH2 and facilitated the formation
of H3K27me3 to inhibit tumor suppression. In this study, we employed a
fluorescence-based method of sugar labeling combined with mass spectrometry to
investigate EZH2 glycosylation and identified five O-GlcNAcylation sites. We also
find that mutation of one or more of the O-GlcNAcylation sites S73A, S76A, S84A,
and T313A in the N-terminal region decreases the stability of EZH2, but does not
affect its association with the PRC2 components SUZ12 and EED. Mutation of the C
terminal O-GlcNAcylation site (S729A) in the catalytic domain of EZH2 abolishes
the di- and trimethylation activities, but not the monomethylation of H3K27, nor
the integrity of the PRC2/EZH2 core complex. Our results show the effect of
individual O-GlcNAcylation sites on the function of EZH2 and suggest an
alternative approach to tumor suppression through selective inhibition of EZH2 O
GlcNAcylation.
PMID- 29941600
TI - Fatty acid metabolism complements glycolysis in the selective regulatory T cell
expansion during tumor growth.
AB - The tumor microenvironment restrains conventional T cell (Tconv) activation while
facilitating the expansion of Tregs. Here we showed that Tregs' advantage in the
tumor milieu relies on supplemental energetic routes involving lipid metabolism.
In murine models, tumor-infiltrating Tregs displayed intracellular lipid
accumulation, which was attributable to an increased rate of fatty acid (FA)
synthesis. Since the relative advantage in glucose uptake may fuel FA synthesis
in intratumoral Tregs, we demonstrated that both glycolytic and oxidative
metabolism contribute to Tregs' expansion. We corroborated our data in human
tumors showing that Tregs displayed a gene signature oriented toward glycolysis
and lipid synthesis. Our data support a model in which signals from the tumor
microenvironment induce a circuitry of glycolysis, FA synthesis, and oxidation
that confers a preferential proliferative advantage to Tregs, whose targeting
might represent a strategy for cancer treatment.
PMID- 29941601
TI - Mutational and transcriptional landscape of spontaneous gene duplications and
deletions in Caenorhabditis elegans.
AB - Gene duplication and deletion are pivotal processes shaping the structural and
functional repertoire of genomes, with implications for disease, adaptation, and
evolution. We employed a mutation accumulation (MA) framework partnered with high
throughput genomics to assess the molecular and transcriptional characteristics
of newly arisen gene copy-number variants (CNVs) in Caenorhabditis elegans
populations subjected to varying intensity of selection. Here, we report a direct
spontaneous genome-wide rate of gene duplication of 2.9 * 10-5/gene per
generation in C. elegans, the highest for any species to date. The rate of gene
deletion is sixfold lower (5 * 10-6/gene per generation). Deletions of highly
expressed genes are particularly deleterious, given their paucity in even the N =
1 lines with minimal efficacy of selection. The increase in average transcript
abundance of new duplicates arising under minimal selection is significantly
greater than twofold compared with single copies of the same gene, suggesting
that genes in segmental duplications are frequently overactive at inception. The
average increase in transcriptional activity of gene duplicates is greater in the
N = 1 MA lines than in MA lines with larger population bottlenecks. There is an
inverse relationship between the ancestral transcription levels of new gene
duplicates and population size, with duplicate copies of highly expressed genes
less likely to accumulate in larger populations. Our results demonstrate a
fitness cost of increased transcription following duplication, which results in
purifying selection against new gene duplicates. However, on average,
duplications also provide a significant increase in gene expression that can
facilitate adaptation to novel environmental challenges.
PMID- 29941602
TI - Targeting beta1-integrin inhibits vascular leakage in endotoxemia.
AB - Loss of endothelial integrity promotes capillary leakage in numerous diseases,
including sepsis, but there are no effective therapies for preserving endothelial
barrier function. Angiopoietin-2 (ANGPT2) is a context-dependent regulator of
vascular leakage that signals via both endothelial TEK receptor tyrosine kinase
(TIE2) and integrins. Here, we show that antibodies against beta1-integrin
decrease LPS-induced vascular leakage in murine endotoxemia, as either a
preventative or an intervention therapy. beta1-integrin inhibiting antibodies
bound to the vascular endothelium in vivo improved the integrity of endothelial
cell-cell junctions and protected mice from endotoxemia-associated cardiac
failure, without affecting endothelial inflammation, serum proinflammatory
cytokine levels, or TIE receptor signaling. Moreover, conditional deletion of a
single allele of endothelial beta1-integrin protected mice from LPS-induced
vascular leakage. In endothelial monolayers, the inflammatory agents thrombin,
lipopolysaccharide (LPS), and IL-1beta decreased junctional vascular endothelial
(VE)-cadherin and induced actin stress fibers via beta1- and alpha5-integrins and
ANGPT2. Additionally, beta1-integrin inhibiting antibodies prevented inflammation
induced endothelial cell contractility and monolayer permeability.
Mechanistically, the inflammatory agents stimulated ANGPT2-dependent
translocation of alpha5beta1-integrin into tensin-1-positive fibrillar adhesions,
which destabilized the endothelial monolayer. Thus, beta1-integrin promotes
endothelial barrier disruption during inflammation, and targeting beta1-integrin
signaling could serve as a novel means of blocking pathological vascular leak.
PMID- 29941603
TI - miR-34a directly targets tRNAiMet precursors and affects cellular proliferation,
cell cycle, and apoptosis.
AB - It remains unknown whether microRNA (miRNA/miR) can target transfer RNA (tRNA)
molecules. Here we provide evidence that miR-34a physically interacts with and
functionally targets tRNAiMet precursors in both in vitro pulldown and Argonaute
2 (AGO2) cleavage assays. We find that miR-34a suppresses breast carcinogenesis,
at least in part by lowering the levels of tRNAiMet through AGO2-mediated
repression, consequently inhibiting the proliferation of breast cancer cells and
inducing cell cycle arrest and apoptosis. Moreover, miR-34a expression is
negatively correlated with tRNAiMet levels in cancer cell lines. Furthermore, we
find that tRNAiMet knockdown also reduces cell proliferation while inducing cell
cycle arrest and apoptosis. Conversely, ectopic expression of tRNAiMet promotes
cell proliferation, inhibits apoptosis, and accelerates the S/G2 transition.
Moreover, the enforced expression of modified tRNAiMet completely restores the
phenotypic changes induced by miR-34a. Our results demonstrate that miR-34a
directly targets tRNAiMet precursors via AGO2-mediated cleavage, and that
tRNAiMet functions as an oncogene, potentially representing a target molecule for
therapeutic intervention.
PMID- 29941604
TI - Design principles for photonic crystals based on plasmonic nanoparticle
superlattices.
AB - Photonic crystals have been widely studied due to their broad technological
applications in lasers, sensors, optical telecommunications, and display devices.
Typically, photonic crystals are periodic structures of touching dielectric
materials with alternating high and low refractive indices, and to date, the
variables of interest have focused primarily on crystal symmetry and the
refractive indices of the constituent materials, primarily polymers and
semiconductors. In contrast, finite difference time domain (FDTD) simulations
suggest that plasmonic nanoparticle superlattices with spacer groups offer an
alternative route to photonic crystals due to the controllable spacing of the
nanoparticles and the high refractive index of the lattices, even far away from
the plasmon frequency where losses are low. Herein, the stopband features of 13
Bravais lattices are characterized and compared, resulting in paradigm-shifting
design principles for photonic crystals. Based on these design rules, a simple
cubic structure with an ~130-nm lattice parameter is predicted to have a broad
photonic stopband, a property confirmed by synthesizing the structure via DNA
programmable assembly and characterizing it by reflectance measurements. We show
through simulation that a maximum reflectance of more than 0.99 can be achieved
in these plasmonic photonic crystals by optimizing the nanoparticle composition
and structural parameters.
PMID- 29941605
TI - Capsid protein structure, self-assembly, and processing reveal morphogenesis of
the marine virophage mavirus.
AB - Virophages have the unique property of parasitizing giant viruses within
unicellular hosts. Little is understood about how they form infectious virions in
this tripartite interplay. We provide mechanistic insights into assembly and
maturation of mavirus, a marine virophage, by combining structural and stability
studies on capsomers, virus-like particles (VLPs), and native virions. We found
that the mavirus protease processes the double jelly-roll (DJR) major capsid
protein (MCP) at multiple C-terminal sites and that these sites are conserved
among virophages. Mavirus MCP assembled in Escherichia coli in the absence and
presence of penton protein, forming VLPs with defined size and shape. While
quantifying VLPs in E. coli lysates, we found that full-length rather than
processed MCP is the competent state for capsid assembly. Full-length MCP was
thermally more labile than truncated MCP, and crystal structures of both states
indicate that full-length MCP has an expanded DJR core. Thus, we propose that the
MCP C-terminal domain serves as a scaffolding domain by adding strain on MCP to
confer assembly competence. Mavirus protease processed MCP more efficiently after
capsid assembly, which provides a regulation mechanism for timing capsid
maturation. By analogy to Sputnik and adenovirus, we propose that MCP processing
renders mavirus particles infection competent by loosening interactions between
genome and capsid shell and destabilizing pentons for genome release into host
cells. The high structural similarity of mavirus and Sputnik capsid proteins
together with conservation of protease and MCP processing suggest that assembly
and maturation mechanisms described here are universal for virophages.
PMID- 29941606
TI - Identification and nanomechanical characterization of the fundamental single
strand protofilaments of amyloid alpha-synuclein fibrils.
AB - The formation and spreading of amyloid aggregates from the presynaptic protein
alpha-synuclein in the brain play central roles in the pathogenesis of
Parkinson's disease. Here, we use high-resolution atomic force microscopy to
investigate the early oligomerization events of alpha-synuclein with single
monomer angstrom resolution. We identify, visualize, and characterize directly
the smallest elementary unit in the hierarchical assembly of amyloid fibrils,
termed here single-strand protofilaments. We show that protofilaments form from
the direct molecular assembly of unfolded monomeric alpha-synuclein polypeptide
chains. To unravel protofilaments' internal structure and elastic properties, we
manipulated nanomechanically these species by atomic force spectroscopy. The
single-molecule scale identification and characterization of the fundamental unit
of amyloid assemblies provide insights into early events underlying their
formation and shed light on opportunities for therapeutic intervention at the
early stages of aberrant protein self-assembly.
PMID- 29941607
TI - Reply to Yoshida: Liver cancer stem cells: Identification and lipid metabolic
reprogramming.
PMID- 29941608
TI - How to eliminate MYCN-positive hepatic cancer stem cells to prevent the
recurrence?
PMID- 29941609
TI - Rise in mortality-when will the government take note?
PMID- 29941610
TI - Analysis of vascular mechanical properties of the yellow anaconda reveals
increased elasticity and distensibility of the pulmonary artery during digestion.
AB - In animals with functional division of blood systemic and pulmonary pressures,
such as mammals, birds, crocodilians and a few non-crocodilian reptiles, the
vessel walls of systemic and pulmonary arteries are exquisitely adapted to endure
different pressures during the cardiac cycle, systemic arteries being stronger
and stiffer than pulmonary arteries. However, the typical non-crocodilian reptile
heart possesses an undivided ventricle that provides similar systolic blood
pressure to both circuits. This raises the question whether in these species the
systemic and pulmonary mechanical vascular properties are similar. Snakes also
display large organ plasticity and increased cardiac output in response to
digestion, and we speculate how the vascular circuit would respond to this
further stress. We addressed these questions by testing the mechanical vascular
properties of the dorsal aorta and the right pulmonary artery of fasted and fed
yellow anacondas, Eunectes notaeus, a snake without functional ventricular
separation that also exhibits large metabolic and cardiovascular responses to
digestion. Similar to previous studies, the dorsal aorta was thicker, stronger,
stiffer and more elastic than the pulmonary artery. However, unlike any other
species studied so far, the vascular distensibility (i.e. the relative volume
change given a pressure change) was similar for the two circuits. Most striking,
the pulmonary artery elasticity (i.e. its capacity to resume its original form
after being stretched) and distensibility increased during digestion, which
suggests that this circuit is remodeled to accommodate the larger stroke volume
and enhance the Windkessel effect, thus providing a more constant blood perfusion
during digestion.
PMID- 29941611
TI - Vocal tract modelling in fallow deer: are male groans nasalized?
AB - Males of several species of deer have a descended and mobile larynx, resulting in
an unusually long vocal tract, which can be further extended by lowering the
larynx during call production. Formant frequencies are lowered as the vocal tract
is extended, as predicted when approximating the vocal tract as a uniform quarter
wavelength resonator. However, formant frequencies in polygynous deer follow
uneven distribution patterns, indicating that the vocal tract configuration may
in fact be rather complex. We CT-scanned the head and neck region of two adult
male fallow deer specimens with artificially extended vocal tracts and measured
the cross-sectional areas of the supra-laryngeal vocal tract along the oral and
nasal tracts. The CT data were then used to predict the resonances produced by
three possible configurations, including the oral vocal tract only, the nasal
vocal tract only, or combining the two. We found that the area functions from the
combined oral and nasal vocal tracts produced resonances more closely matching
the formant pattern and scaling observed in fallow deer groans than those
predicted by the area functions of the oral vocal tract only or of the nasal
vocal tract only. This indicates that the nasal and oral vocal tracts are both
simultaneously involved in the production of a non-human mammal vocalization, and
suggests that the potential for nasalization in putative oral loud calls should
be carefully considered.
PMID- 29941613
TI - Trade-offs between immunity and testosterone in male African ground squirrels.
AB - The immunocompetence handicap hypothesis (ICHH) proposes that testosterone has
both beneficial effects on male reproductive potential and negative effects by
suppressing the immune system. However, support for the ICHH has been variable
and an alternative hypothesis suggests that testosterone may be acting indirectly
via cortisol to suppress immunity (the stress-linked ICHH). A third hypothesis is
that increased energetic investment in immunity results in the suppression of
testosterone. We tested these hypotheses in male Cape ground squirrels (Xerus
inauris) through two separate manipulations: first, by triggering a strong immune
response using a lipopolysaccharide (LPS) injection and, secondly, by increasing
circulating testosterone using silastic testosterone implants. Responding to an
immune challenge significantly reduced testosterone, supporting the immune
suppression hypothesis, while increasing circulating testosterone had no effect
on immunocompetence, body mass, ectoparasite abundances or cortisol levels,
failing to support either the ICHH or stress-linked ICHH. Our results add to the
increasing body of literature that challenges the ICHH, and we conclude that the
trade-off between testosterone and immunity is mediated through immune activation
and not through testosterone in male Cape ground squirrels. Being able to test
the ICHH, stress-linked ICHH and immune suppression hypotheses in a free-ranging
mammal gives us a unique opportunity to examine the mechanisms mediating this
trade-off.
PMID- 29941612
TI - Waddle and shuffle: gait alterations associated with domestication in turkeys.
AB - Domestication has altered turkey morphology by artificially selecting for
increased muscle mass and breast meat. Artificial selection has resulted in birds
that weigh up to 3 times more than their wild counterparts, with relatively
little change in the length of their bones and limbs. Considering these
structural changes, it seems probable that domestic turkey locomotor kinematics
and kinetics would also be altered. To examine the locomotor dynamics of wild and
domestic turkeys, we had both strains walk down a runway with a force plate at
the center to measure their ground reaction forces and gait parameters. The
location of their center of mass was also quantified using a force plate and bi
planar x-ray and found to be further anterior in the domestic strain. The
domestic turkeys locomoted across a lower range of speeds (0.25-1.64 ms-1) than
the wild turkeys (0.26-3.26 ms-1) and increased their stride frequency at a
higher rate. They also displayed large lateral oscillations, i.e. waddling,
during walking that translated into relatively high medio-lateral ground reaction
forces and lateral kinetic energy (3.5 times higher than that of wild turkeys).
The results indicate that domestic turkey locomotion is not simply a slowed down
version of wild turkey locomotion. The changes in gait observed are similar to
the shuffling gait present in some human populations, such as Parkinson's
patients, which serves to increase stability. The domestic turkey's increased
body mass and more anterior center of mass position may require these kinematic
and kinetic gait differences.
PMID- 29941614
TI - Cellular mechanisms of slime gland refilling in Pacific hagfish (Eptatretus
stoutii).
AB - Hagfishes use their defensive slime to ward off gill-breathing predators. Slime
gland refilling is a surprisingly slow process, and previous research has shown
that the composition of the slime exudate changes significantly during refilling,
which likely has consequences for the functionality of the slime. This study set
out to expand our understanding of slime gland refilling by examining the
cellular processes involved in refilling of the glands, as well as determining
where in the gland the main slime cells - the gland thread cells and gland mucous
cells - arise. Slime glands were electro-stimulated to exhaust their slime
stores, left to refill for set periods of time, and harvested for histological
and immunohistochemical examination. Whole slime glands, gland thread cell
morphometrics and slime cell proportions were examined over the refilling cycle.
Slime glands decreased significantly in size after exhaustion, but steadily
increased in size over refilling. Gland thread cells were the limiting factor in
slime gland refilling, taking longer to replenish and mature than gland mucous
cells. Newly produced gland thread cells underwent most of their growth near the
edge of the gland, and larger cells were found farthest from the edge of the
gland. Immunohistochemical analysis also revealed proliferating cells only within
the epithelial lining of the slime gland, suggesting that new slime cells
originate from undifferentiated cells lining the gland. Our results provide an in
depth look at the cellular dynamics of slime gland refilling in Pacific hagfish,
and provide a model for how slime glands refill at the cellular level.
PMID- 29941615
TI - Limits to sustained energy intake. XXVIII. Beneficial effects of high dietary fat
on lactation performance in mice.
AB - Maximal animal performance may be limited by the ability of an animal to
dissipate heat: the heat dissipation limitation (HDL) theory. Because the
incidental heat produced during digestion [specific dynamic action (SDA)] varies
among diets, the HDL theory predicts that lactating female mice consuming diets
with lower SDA should have increased reproductive performance. Dietary fat has a
lower SDA than dietary carbohydrate. Female mice were fed low (LF), medium (MF)
or high (HF) fat diets (10, 45 and 60% energy from fat, respectively) from days 4
18 of lactation. HF- and MF-fed mice weaned significantly heavier litters than LF
mice. This was because they not only consumed more energy [metabolisable energy
intake (Emei); HF: 306.5+/-25.0, MF: 340.5+/-13.5 kJ day-1] at peak lactation,
but also delivered more milk energy to their pups [milk energy output (Emilk);
HF: 203.2+/-49.9, MF 229.3+/-42.2 kJ day-1] than the LF-fed mice (Emei=266.7+/
4.5, Emilk=164.60+/-30.59 kJ day-1). A mathematical model based on the
predictions from the HDL theory showed that this effect was greater than
predicted from differences in SDA between the diets. Fatty acid profiles of the
diets, milk and pups showed significant correlations between the profiles.
Besides reduced SDA, HF- and MF-fed mice were probably able to directly transfer
absorbed dietary fat into milk, reducing the heat production of lactogenesis and
enabling them to perform better than expected from the HDL model. In summary, HF
and MF diets had beneficial effects on reproductive performance compared with the
LF diet because they enabled mice to generate milk more efficiently with less
incidental heat production.
PMID- 29941617
TI - Scrap NHS competition rules, BMA says.
PMID- 29941616
TI - An in vivo test of the biologically relevant roles of carotenoids as antioxidants
in animals.
AB - Carotenoids are well known for their contribution to the vibrant coloration of
many animals and have been hypothesized to be important antioxidants.
Surprisingly few examples of carotenoids acting as biologically relevant
antioxidants in vivo exist, in part because experimental designs often employ
carotenoid doses at levels that are rarely observed in nature. Here, we used an
approach that reduces carotenoid content from wild-type levels to test for the
effect of carotenoids as protectants against an oxidative challenge. We used the
marine copepod Tigriopus californicus reared on a carotenoid-free or a carotenoid
restored diet of nutritional yeast and then exposed them to a pro-oxidant. We
found that carotenoid-deficient copepods not only accumulated more damage but
also were more likely to die during an oxidative challenge than carotenoid
restored copepods. We suggest that carotenoid reduction, and not supplementation,
better tests the proposed roles of carotenoids in other physiological functions
in animals.
PMID- 29941618
TI - Is it time to reframe how we care for people with non-traumatic musculoskeletal
pain?
PMID- 29941620
TI - What can Andreev bound states tell us about superconductors?
AB - Zero-energy Andreev bound states, which manifest themselves in the tunnelling
spectra as zero-bias conductance peaks (ZBCPs), are abundant at interfaces
between superconductors and other materials and on the nodal surface of high
temperature superconductors. In this review, we focus on the information such
excitations can provide on the properties of superconductor systems. First, a
general introduction to the physics of Andreev bound states in
superconductor/normal metal interfaces is given with a particular emphasis on why
they appear at zero energy in d-wave superconductors. Then, specific
spectroscopic tunnelling studies of thin films, bilayers and junctions are
described, focusing on the corresponding ZBCP features. Scanning tunnelling
spectroscopy (STS) studies show that the ZBCPs on the c-axis YBa2Cu3O7-delta
(YBCO) films are correlated with the surface morphology and appear only in
proximity to (110) facets. STS on c-axis La1.88Sr0.12CuO4 (LSCO) films exhibiting
the 1/8 anomaly shows spatially modulated peaks near zero bias associated with
the anti-phase ordering of the d-wave order parameter predicted at this doping
level. ZBCPs were also found in micrometre-size edge junctions of
YBCO/SrRuO3/YBCO, where SrRuO3 is ferromagnetic. Here, the results are consistent
with a crossed Andreev reflection effect (CARE) at the narrow domain walls of the
SrRuO3 ZBCPs measured in STS studies of manganite/cuprate bilayers could not be
attributed to CARE because the manganite's domain wall is much larger than the
coherence length in YBCO, and instead are attributed to proximity-induced triplet
pairing superconductivity with non-conventional symmetry. And finally, ZBCPs
found in junctions of non-intentionally doped topological insulator films of
Bi2Se3 and the s-wave superconductor NbN are attributed to proximity-induced px +
ipy triplet order parameter in the topological material.This article is part of
the theme issue 'Andreev bound states'.
PMID- 29941621
TI - Andreev reflection spectroscopy in transition metal oxides.
AB - Here we review the literature concerning measurement of the Andreev reflection
between a superconductor (S) and ferromagnet (F), with particular attention to
the case where the ferromagnet is a transition metal oxide. We discuss the
practicality of utilization of the current models for determination of the
transport current spin polarization and examine the evidence for Andreev bound
states.This article is part of the theme issue 'Andreev bound states'.
PMID- 29941619
TI - Initiation of Meiotic Development Is Controlled by Three Post-transcriptional
Pathways in Caenorhabditis elegans.
AB - A major event in germline development is the transition from stem/progenitor
cells to entry into meiosis and gametogenesis. This transition requires
downregulation of mitotic cell cycle activity and upregulation of processes
associated with meiosis. We identify the Caenorhabditis elegans SCFPROM-1 E3
ubiquitin-ligase complex as functioning to downregulate mitotic cell cycle
protein levels including cyclin E, WAPL-1, and KNL-2 at meiotic entry and,
independently, promoting homologous chromosome pairing as a positive regulator of
the CHK-2 kinase. SCFPROM-1 is thus a novel regulator of meiotic entry,
coordinating downregulation of mitotic cell cycle proteins and promoting homolog
pairing. We further show that SCFPROM-1 functions redundantly, in parallel to the
previously described GLD-1 and GLD-2 meiotic entry pathways, downstream of and
inhibited by GLP-1 Notch signaling, which specifies the stem cell fate.
Accordingly, C. elegans employs three post-transcriptional pathways, SCFPROM-1
mediated protein degradation, GLD-1-mediated translational repression, and GLD-2
mediated translational activation, to control and coordinate the initiation of
meiotic development.
PMID- 29941622
TI - Andreev bound states at spin-active interfaces.
AB - Andreev bound states are ubiquitous in superconducting hybrid structures. They
are formed near impurities, in Josephson junctions, in vortex cores and at
interfaces. At spin-active superconductor-ferromagnet interfaces, Andreev bound
states are formed due to spin-dependent scattering phases. Spin-dependent phase
shifts are an important ingredient for the generation of triplet Cooper pairs in
superconductor-ferromagnet hybrid structures. Spectroscopy of Andreev bound
states is a powerful probe of superconducting order parameter symmetry, as well
as spin-dependent interface scattering and the triplet proximity effect.This
article is part of the theme issue 'Andreev bound states'.
PMID- 29941623
TI - Andreev bound states in superconducting films and confined superfluid 3He.
AB - This paper reviews confinement-driven phase transitions in superconductors and
Bardeen-Cooper-Schrieffer superfluids, and the appearance in thin films of new
phases that break the time-reversal or translational symmetry. The origins of the
new phases are closely tied to the Andreev scattering processes involving
particle-hole conversions that create surface quasiparticle states with energies
inside the superconducting gap. Restructuring of the low-energy spectrum in the
surface region of several coherence lengths xi0 results in large spatial
variations of the superconducting order parameter. In confined geometry, such as
slabs, films, pores or nano-dots, with one or more physical dimensions D~10xi0,
the Andreev bound states can dominate properties of a superconductor, leading to
modified experimental signatures. They can significantly change the energy
landscape, and drive transitions into new superconducting phases. The new phases
are expected in a variety of materials, from singlet d-wave superconductors to
multi-component triplet superfluid 3He, but properties of the new phases will
depend on the symmetry of the parent state. I will highlight the connection
between the Andreev surface states and confinement-stabilized phases with
additional broken symmetries, describe recent progress and open questions in the
theoretical and experimental investigation of superfluids in confined
geometry.This article is part of the theme issue 'Andreev bound states'.
PMID- 29941624
TI - Theory of Andreev bound states in S-F-S junctions and S-F proximity devices.
AB - Andreev bound states are an expression of quantum coherence between particles and
holes in hybrid structures composed of superconducting and non-superconducting
metallic parts. Their spectrum carries important information on the nature of the
pairing, and determines the current in Josephson devices. Here, I focus on
Andreev bound states in systems involving superconductors and ferromagnets with
strong spin-polarization. I provide a general framework for non-local Andreev
phenomena in such structures in terms of coherence functions, and show how the
latter link wave function and Green-function based theories.This article is part
of the theme issue 'Andreev bound states'.
PMID- 29941625
TI - Spin-triplet supercurrents in Josephson junctions containing strong ferromagnetic
materials.
AB - The proximity effect between a superconducting material and a non-superconducting
normal metal can extend over distances of the order of micrometres at
sufficiently low temperatures. If the normal metal is replaced by a ferromagnetic
material, the spatial extent of the proximity effect drops precipitously due to
the exchange splitting between the majority and minority spin bands in the
ferromagnet. In 2001, several theorists predicted that spin-triplet pair
correlations could be induced in proximity systems involving multiple
ferromagnetic materials (or multiple domains in one material) with non-collinear
magnetizations. Such spin-triplet pair correlations should extend deep into the
ferromagnet, producing a long-range proximity effect. In this paper, we review
our experimental work in this area, which has focused primarily on Josephson
junctions containing strong ferromagnetic materials. We show that Josephson
junctions containing particular combinations of strong ferromagnetic materials
can carry spin-triplet supercurrent over distances of at least several tens of
nanometres, whereas spin-singlet supercurrent in similar samples decays over a
length scale of about 1 nm. We also mention important work by other groups;
however, this article is not intended to be a review of the whole field.This
article is part of the theme issue 'Andreev bound states'.
PMID- 29941626
TI - Weyl nodes in periodic structures of superconductors and spin-active materials.
AB - Motivated by recent progress in epitaxial growth of proximity structures of s
wave superconductors (S) and spin-active materials (M), in this paper we show
that certain periodic structures of S and M can behave effectively as
superconductors with pairs of point nodes, near which the low-energy excitations
are Weyl fermions. A simple model, where M is described by a Kronig-Penney
potential with both spin-orbit coupling and exchange field, is proposed and
solved to obtain the phase diagram of the nodal structure, the spin texture of
the Weyl fermions, as well as the zero-energy surface states in the form of open
Fermi lines (Fermi arcs). As a second example, a lattice model with alternating
layers of S and magnetic Z2 topological insulators is solved. The calculated
spectrum confirms previous predictions of Weyl nodes based on the tunnelling
Hamiltonian of Dirac electrons. Our results provide further evidence that
periodic structures of S and M are well suited for engineering gapless
topological superconductors.This article is part of the theme issue 'Andreev
bound states'.
PMID- 29941627
TI - Non-equilibrium charge and spin transport in superconducting-ferromagnetic
superconducting point contacts.
AB - The conventional Josephson effect may be modified by introducing spin-active
scattering in the interface layer of the junction. Here, we discuss a Josephson
junction consisting of two s-wave superconducting leads coupled over a classical
spin that precesses with the Larmor frequency due to an external magnetic field.
This magnetically active interface results in a time-dependent boundary condition
with different tunnelling amplitudes for spin-up and -down quasi-particles and
where the precession produces spin-flip scattering processes. As a result, the
Andreev states develop sidebands and a non-equilibrium population that depend on
the details of the spin precession. The Andreev states carry a steady-state
Josephson charge current and a time-dependent spin current, whose current-phase
relations could be used to characterize the precessing spin. The spin current is
supported by spin-triplet correlations induced by the spin precession and creates
a feedback effect on the classical spin in the form of a torque that shifts the
precession frequency. By applying a bias voltage, the Josephson frequency adds
another complexity to the situation and may create resonances together with the
Larmor frequency. These Shapiro resonances manifest as torques and, under
suitable conditions, are able to reverse the direction of the classical spin in
sub-nanosecond time. Another characteristic feature is the subharmonic gap
structure in the DC charge current displaying an even-odd effect attributable to
precession-assisted multiple Andreev reflections.This article is part of the
theme issue 'Andreev bound states'.
PMID- 29941628
TI - Study on Green's function on topological insulator surface.
AB - In the theory of superconducting junctions, Green's function has an important
role for obtaining Andreev bound states, local density of states and Josephson
current in a systematic way. In this article, we show how to construct Green's
function on the surface of a topological insulator following McMillan's formalism
where the energy spectrum of electrons obeys a linear dispersion. For a model of
a superconductor (S)/ferromagnet (F)/normal metal (N) junction, we show that the
generation of a Majorana fermion gives rise to the enhanced local density of
states and pair amplitude of odd-frequency pairing. We also derive an extended
Furusaki-Tsukada's formula of DC Josephson current in S/F/S junctions. The
obtained Josephson current depends on the direction and magnitude of the
magnetization.This article is part of the theme issue 'Andreev bound states'.
PMID- 29941629
TI - Out-of-equilibrium spin transport in mesoscopic superconductors.
AB - The excitations in conventional superconductors, Bogoliubov quasi-particles, are
spin-[Formula: see text] fermions but their charge is energy-dependent and, in
fact, zero at the gap edge. Therefore, in superconductors (unlike normal metals)
spin and charge degrees of freedom may be separated. In this article, we review
spin injection into conventional superconductors and focus on recent experiments
on mesoscopic superconductors. We show how quasi-particle spin transport and out
of-equilibrium spin-dependent superconductivity can be triggered using the Zeeman
splitting of the quasi-particle density of states in thin-film superconductors
with small spin-mixing scattering. Finally, we address the spin dynamics and the
feedback of quasi-particle spin imbalances on the amplitude of the
superconducting energy gap.This article is part of the theme issue 'Andreev bound
states'.
PMID- 29941630
TI - Multifaceted properties of Andreev bound states: interplay of symmetry and
topology.
AB - Andreev bound states (ABSs) ubiquitously emerge as a consequence of non-trivial
topological structures of the order parameter of superfluids and superconductors
and significantly contribute to thermodynamics and low-energy quantum transport
phenomena. We here share the current status of our knowledge on their
multifaceted properties such as Majorana fermions and odd-frequency pairing. A
unified concept behind ABSs originates from a soliton state in the one
dimensional Dirac equation with mass domain wall and interplay of ABSs with
symmetry and topology enrich their physical characteristics. We make an overview
of ABSs with a special focus on superfluid 3He. The quantum liquid confined to
restricted geometries serves as a rich repository of noteworthy quantum
phenomena, such as the mass acquisition of Majorana fermions driven by
spontaneous symmetry breaking, topological quantum criticality, Weyl
superfluidity and the anomalous magnetic response. The marriage of the superfluid
3He and nano-fabrication techniques will take one to a new horizon of topological
quantum phenomena associated with ABSs.This article is part of the theme issue
'Andreev bound states'.
PMID- 29941631
TI - Correction to 'Building equity in: strategies for integrating equity into
modelling for a 1.5 degrees C world'.
PMID- 29941632
TI - Andreev bound states and their signatures.
AB - Many of the properties of superconductors related to quantum coherence are
revealed when the superconducting state is forced to vary in space in response to
an external magnetic field, a proximity contact, an interface to a ferromagnet or
to impurities embedded in the superconductor. Among the earliest examples is
Andreev reflection of an electron into a retro-reflected hole at a normal
superconducting interface. In regions of strong inhomogeneity, multiple Andreev
reflection leads to the formation of sub-gap states, Andreev bound states, with
excitation energies below the superconducting gap. These states play a central
role in our understanding of inhomogeneous superconductors. The discoveries of
unconventional superconductivity in many classes of materials, advances in
fabrication of superconducting/ferromagnetic hybrids and nanostructures for
confining superfluid 3 He, combined with theoretical developments in topological
quantum matter have dramatically expanded the significance of branch conversion
scattering and Andreev bound state formation. This collection of articles
highlights developments in inhomogeneous superconductivity, unconventional
superconductivity and topological phases of superfluid 3 He, in which Andreev
scattering and bound states underpin much of the physics of these systems. This
article provides an introduction to the basic physics of Andreev scattering,
bound-state formation and their signatures. The goal is both an introduction for
interested readers who are not already experts in the field, and to highlight
examples in which branch conversion scattering and Andreev bound states provide
unique signatures in the transport properties of superconductors.This article is
part of the theme issue 'Andreev bound states'.
PMID- 29941633
TI - Limiting access to lethal means: applying the social ecological model for firearm
suicide prevention.
AB - This paper outlines a novel application of the social ecological model (SEM) for
firearm suicide prevention. It focuses on four levels of intervention (societal,
relationship, community and individual) to reduce access to firearms, a practical
contributor to the capacity to attempt suicide, from individuals when they are at
an elevated risk for suicide. There is substantive research linking easy access
to firearms with an increased risk of firearm suicide, and suicide prevention
interventions that address access to lethal means are critical components of a
comprehensive suicide prevention strategy. Potential interventions using the SEM
framework include: at the policy level-extreme risk laws, voluntary self
prohibition policies and policies that reduce the availability of firearms; at
the community level-gun shop projects; at the relationship level-lethal means
safety counselling; and at the individual level-safer storage. Taken together
with upstream interventions, such as increased access to mental health services
and substance use treatment, a multilevel approach for suicide prevention that
addresses access to firearms can save lives.
PMID- 29941634
TI - Liver blood dynamics after bariatric surgery: the effects of mixed-meal test and
incretin infusions.
AB - AIMS/HYPOTHESIS: The mechanisms for improved glycemic control after bariatric
surgery in subjects with type 2 diabetes (T2D) are not fully known. We
hypothesized that dynamic hepatic blood responses to a mixed-meal are changed
after bariatric surgery in parallel with an improvement in glucose tolerance.
METHODS: A total of ten morbidly obese subjects with T2D were recruited to
receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP)
infusion before and early after (within a median of less than three months)
bariatric surgery, and hepatic blood flow and volume (HBV) were measured
repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic
individuals served as controls. RESULTS: Bariatric surgery leads to a significant
decrease in weight, accompanied with an improved beta-cell function and glucagon
like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in
portal vein (PV) was increased by 1.65-fold (P = 0.026) in response to a mixed
meal in subjects after surgery, while HBV decreased in all groups (P < 0.001).
When the effect of GIP infusion was tested separately, no change in hepatic
arterial and PV flow was observed, but HBV decreased as seen during the mixed
meal test. CONCLUSIONS/INTERPRETATION: Early after bariatric surgery, PV flow
response to a mixed-meal is augmented, improving digestion and nutrient
absorption. GIP influences the post-prandial reduction in HBV thereby diverting
blood to the extrahepatic sites.
PMID- 29941635
TI - UCT943, a Next-Generation Plasmodium falciparum PI4K Inhibitor Preclinical
Candidate for the Treatment of Malaria.
AB - The 2-aminopyridine MMV048 was the first drug candidate inhibiting Plasmodium
phosphatidylinositol 4-kinase (PI4K), a novel drug target for malaria, to enter
clinical development. In an effort to identify the next generation of PI4K
inhibitors, the series was optimized to improve properties such as solubility and
antiplasmodial potency across the parasite life cycle, leading to the 2
aminopyrazine UCT943. The compound displayed higher asexual blood stage,
transmission-blocking, and liver stage activities than MMV048 and was more potent
against resistant Plasmodium falciparum and Plasmodium vivax clinical isolates.
Excellent in vitro antiplasmodial activity translated into high efficacy in
Plasmodium berghei and humanized P. falciparum NOD-scid IL-2Rgamma null mouse
models. The high passive permeability and high aqueous solubility of UCT943,
combined with low to moderate in vivo intrinsic clearance, resulted in sustained
exposure and high bioavailability in preclinical species. In addition, the
predicted human dose for a curative single administration using monkey and dog
pharmacokinetics was low, ranging from 50 to 80 mg. As a next-generation
Plasmodium PI4K inhibitor, UCT943, based on the combined preclinical data, has
the potential to form part of a single-exposure radical cure and prophylaxis
(SERCaP) to treat, prevent, and block the transmission of malaria.
PMID- 29941637
TI - Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding
Protein 2a of Methicillin-Resistant Staphylococcus aureus.
AB - A total of 281 nonduplicated Staphylococcus aureus blood isolates were collected
from January to May 2017 from eight hospitals in South Korea to investigate the
epidemiological traits of ceftaroline resistance in methicillin-resistant S.
aureus (MRSA). Cefoxitin-disk diffusion tests and the mecA gene PCR revealed that
56.6% (159/281) of the S. aureus isolates were MRSA, and most belonged to ST5
(50.3%, 80/281) and ST72 (41.5%, 66/281). Of the MRSA isolates, 44.0% (70/159)
were nonsusceptible to ceftaroline (MIC >= 2 mg/liter), whereas all of the
methicillin-susceptible S. aureus isolates were susceptible to the drug. Eight
amino acid substitutions in penicillin-binding protein 2a (PBP2a), including four
(L357I, E447K, I563T, and S649A) in the penicillin-binding domain (PBD) and four
(N104K, V117I, N146K, and A228V) in the non-PBD (nPBD) of PBP2a, were associated
with ceftaroline resistance. The accumulation of substitutions in PBP2a resulted
in the elevation of ceftaroline MICs: one substitution at 1 to 2 mg/liter, two or
three substitutions at 2 to 4 mg/liter, and five substitutions at 4 or 16
mg/liter. Ceftaroline resistance in MRSA might be the result of clone-specific
PBP2a polymorphism, along with substitutions both in PBD and nPBD, and the
elevated ceftaroline MICs were associated with the substitution sites and
accumulation of substitutions.
PMID- 29941636
TI - Validating a 14-Drug Microtiter Plate Containing Bedaquiline and Delamanid for
Large-Scale Research Susceptibility Testing of Mycobacterium tuberculosis.
AB - The UKMYC5 plate is a 96-well microtiter plate designed by the CRyPTIC Consortium
(Comprehensive Resistance Prediction for Tuberculosis: an International
Consortium) to enable the measurement of MICs of 14 different antituberculosis
(anti-TB) compounds for >30,000 clinical Mycobacterium tuberculosis isolates.
Unlike the MYCOTB plate, on which the UKMYC5 plate is based, the UKMYC5 plate
includes two new (bedaquiline and delamanid) and two repurposed (clofazimine and
linezolid) compounds. UKMYC5 plates were tested by seven laboratories on four
continents by use of a panel of 19 external quality assessment (EQA) strains,
including H37Rv. To assess the optimal combination of reading method and
incubation time, MICs were measured from each plate by two readers, using three
methods (mirrored box, microscope, and Vizion digital viewing system), after 7,
10, 14, and 21 days of incubation. In addition, all EQA strains were subjected to
whole-genome sequencing and phenotypically characterized by the 7H10/7H11 agar
proportion method (APM) and by use of MGIT960 mycobacterial growth indicator
tubes. We concluded that the UKMYC5 plate is optimally read using the Vizion
system after 14 days of incubation, achieving an interreader agreement of 97.9%
and intra- and interlaboratory reproducibility rates of 95.6% and 93.1%,
respectively. The mirrored box had a similar reproducibility. Strains classified
as resistant by APM, MGIT960, or the presence of mutations known to confer
resistance consistently showed elevated MICs compared to those for strains
classified as susceptible. Finally, the UKMYC5 plate records intermediate MICs
for one strain for which the APM measured MICs close to the applied critical
concentration, providing early evidence that the UKMYC5 plate can quantitatively
measure the magnitude of resistance to anti-TB compounds that is due to specific
genetic variation.
PMID- 29941638
TI - The Orotomide Olorofim Is Efficacious in an Experimental Model of Central Nervous
System Coccidioidomycosis.
AB - Olorofim (formerly F901318) is an advanced analog of the orotomide class that
inhibits fungal pyrimidine biosynthesis. We evaluated the in vitro and in vivo
activities of olorofim against Coccidioides species. In vitro activity was
assessed against 59 clinical Coccidioides isolates. Central nervous system
infections were established in mice via intracranial inoculation with
Coccidioides immitis arthroconidia. Oral therapy began 48 h postinoculation and
consisted of vehicle control, olorofim daily doses of 20 mg/kg (6.67 mg/kg three
times daily or 10 mg/kg twice daily) or 40 mg/kg (13.3 mg/kg three times daily or
20 mg/kg twice daily), or fluconazole (25 mg/kg twice daily). Treatment continued
for 7 and 14 days in the fungal burden and survival arms, respectively. Fungal
burdens were assessed by CFU counts in brains. Olorofim demonstrated potent in
vitro activity (MIC range, <=0.008 to 0.06 MUg/ml). Survival was significantly
enhanced in mice treated with olorofim. Reductions in brain tissue fungal burdens
were also observed on day 9 in the olorofim-treated groups. Improvements in
survival and reductions in fungal burdens also occurred with fluconazole. More
frequent dosing of olorofim was associated with enhanced survival and greater
reductions in fungal burdens. In the group treated with 13.3 mg/kg olorofim three
times daily, fungal burdens remained low on day 30 (15 days after treatment was
stopped), with undetectable levels in 7 of 10 mice. In contrast, fungal burdens
rebounded in all other groups after therapy stopped. Olorofim was highly active
in vitro and in vivo against Coccidioides These results demonstrate that olorofim
may have a role in the treatment of coccidioidomycosis.
PMID- 29941639
TI - Variability of Daptomycin MIC Values for Enterococcus faecium When Measured by
Reference Broth Microdilution and Gradient Diffusion Tests.
AB - Daptomycin has become a mainstay therapy for the treatment of serious vancomycin
resistant Enterococcus faecium infections. However, concern exists that current
testing methods do not accurately predict the clinical success of daptomycin
therapy. We evaluated a collection of 40 isolates of E. faecium across three
centers by reference broth microdilution (BMD), and two gradient strips, to
determine the precision of daptomycin MICs by these methods and the correlation
of daptomycin MIC testing with mutations in the liaFSR system, one of the primary
daptomycin resistance mechanisms among the enterococci. Daptomycin MICs spanned 3
log2 dilutions by BMD for 60.0% of isolates, 17.5% spanned 4 dilutions, 2.5%
spanned 5 dilutions, and 20.0% spanned 6 or more dilutions. Fifteen isolates had
MICs interpreted as susceptible by some tests and nonsusceptible by others.
Neither BMD nor gradient diffusion tests could reliably differentiate isolates
with or without mutations in liaFSR, resulting in a 59.8% very major error rate
compared to determination of genotype by BMD, 63.5% by Etest, and 68.5% by MIC
test strip. Imprecision in daptomycin MIC determination for E. faecium make
establishment of a revised breakpoint challenging. Clinicians should be aware of
this testing variability when making treatment decisions for patients with
serious infections caused by this organism.
PMID- 29941641
TI - Acquisition of Beta-Lactamase by Neisseria meningitidis through Possible
Horizontal Gene Transfer.
AB - We report the detection in France of a beta-lactamase-producing invasive
meningococcal isolate. Whole-genome sequencing of the isolate revealed a ROB-1
type beta-lactamase gene that is frequently encountered in Haemophilus
influenzae, suggesting horizontal transfer between isolates of these bacterial
species. Beta-lactamases are exceptional in meningococci, with no reports for
more than 2 decades. This report is worrying, as the expansion of such isolates
may jeopardize the effective treatment against invasive meningococcal disease.
PMID- 29941640
TI - Screening and Characterization of Multidrug-Resistant Gram-Negative Bacteria from
a Remote African Area, Sao Tome and Principe.
AB - The occurrence of resistance to last-resort antibiotics was evaluated among
Enterobacteriaceae isolates recovered from hospitalized children in a remote
African archipelago, Sao Tome and Principe, where there is limited access to
those antibiotics. Fifty patients were screened for colonization by carbapenem-,
pan-aminoglycoside-, or polymyxin-resistant Enterobacteriaceae A total of 36
isolates (including 30 Escherichia coli and 4 Klebsiella pneumoniae) were
recovered from 23 patients, including 26 isolates harboring the blaOXA-181
carbapenemase gene, a single isolate harboring the 16S rRNA methylase gene rmtB
encoding pan-resistance to aminoglycosides, and 8 isolates coharboring both
genes. A single isolate possessed the plasmid-borne colistin resistance gene mcr
1 A high clonal relationship was found for OXA-181-producing E. coli (4 clones),
and conversely, three of the four OXA-181-producing K. pneumoniae isolates were
clonally unrelated. This study overall showed a high prevalence of resistance to
last-resort antibiotics in this country, where no epidemiological data were
previously available.
PMID- 29941642
TI - Reversal of Chloroquine Resistance of Plasmodium vivax in Aotus Monkeys.
AB - Chloroquine-resistant (CQR) vivax malaria has emerged as a threat to the malaria
elimination agenda. The objective of this study was to assess if a combination of
chloroquine (CQ) and prochlorperazine was able to reverse CQ resistance of the
Plasmodium vivax AMRU-1 strain from Papua New Guinea in infected Aotus monkeys.
For this purpose, in two independent experimental drug efficacy trials, a total
of 18 Aotus monkeys infected with blood obtained from donor animals were randomly
assigned to treatment and control groups and orally administered CQ at 10 mg/kg
or prochlorperazine at 20 mg/kg, alone or in combination, for five consecutive
days. Reversal of CQR was achieved in animals that received the drug combination,
whereas neither drug alone produced cures. This same drug combination reverses
CQR in P. falciparum and could be an alternative for treatment in humans with
chloroquine-resistant P. vivax infections.
PMID- 29941644
TI - Molecular Analysis of Resistance and Detection of Non-Wild-Type Strains Using
Etest Epidemiological Cutoff Values for Amphotericin B and Echinocandins for
Bloodstream Candida Infections from a Tertiary Hospital in Qatar.
AB - A total of 301 Candida bloodstream isolates collected from 289 patients over 5
years at a tertiary hospital in Qatar were evaluated. Out of all Candida
infections, 53% were diagnosed in patients admitted to the intensive care units.
Steady increases in non-albicans Candida species were reported from 2009 to 2014
(30.2% for Candida albicans versus 69.8% for the other Candida species). Etest
antifungal susceptibility testing was performed on all recovered clinical
isolates to determine echinocandin (micafungin and anidulafungin) and
amphotericin B susceptibilities and assess non-wild-type (non-WT) strains
(strains for which MICs were above the epidemiological cutoff values). DNA
sequence analysis was performed on all isolates to assess the presence of FKS
mutations, which confer echinocandin resistance in Candida species. A total of
3.9% of isolates (12/301) among strains of C. albicans and C. orthopsilosis
contained FKS hot spot mutations, including heterozygous mutations in FKS1 For C.
tropicalis, the Etest appeared to overestimate strains non-WT for micafungin,
anidulafungin, and amphotericin B, as 14%, 11%, and 35% of strains, respectively,
had values above the epidemiological cutoff value. However, no FKS mutations were
identified in this species. For all other species, micafungin best reported the
echinocandin non-WT strains relative to the FKS genotype, as anidulafungin tended
to overestimate non-wild-type strains. Besides C. tropicalis, few strains were
classified as non-WT for amphotericin B.
PMID- 29941645
TI - Surveillance of Genetic Variations Associated with Antimalarial Resistance of
Plasmodium falciparum Isolates from Returned Migrant Workers in Wuhan, Central
China.
AB - Antimalarial drug resistance developed in Plasmodium falciparum has become a
problem for malaria control. Evaluation of drug resistance is the first step for
effective malaria control. In this study, we investigated the gene mutations of
P. falciparum using blood samples from returned Chinese migrant workers in order
to identify drug resistance-associated molecular markers. These workers returned
from Africa and Southeast Asia (SEA) during 2011 to 2016. Polymorphisms in pfcrt,
pfmdr1, and k13-propeller genes and the haplotype patterns of Pfcrt and Pfmdr1
were analyzed. The results showed the presence of four haplotypes of Pfcrt codons
72 to 76, including CVMNK (wild type), SVMNT and CVIET (mutation types), and CV
M/I N/E K/T (mixed type), with 50.57%, 1.14%, 25.00%, and 23.30% prevalence,
respectively. For Pfmdr1, N86Y (22.28%) and Y184F (60.01%) were the main
prevalent mutations (mutations are underlined). The prevalence of mutation at
position 550, 561, 575, and 589 of K13-propeller were 1.09%, 0.54%, 0.54%, and
0.54%, respectively. These data suggested that Pfcrt, Pfmdr1, and K13-propeller
polymorphisms are potential markers to assess drug resistance of P. falciparum in
China, Africa, and SEA.
PMID- 29941643
TI - Molecular Identification and Susceptibility Testing of Molds Isolated in a
Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study).
AB - Antifungal resistance is increasing by the emergence of intrinsically resistant
species and by the development of secondary resistance in susceptible species. A
previous study performed in Spain revealed levels of azole resistance in molds of
between 10 and 12.7%, but secondary resistance in Aspergillus fumigatus was not
detected. We used itraconazole (ITZ)-supplemented medium to select resistant
strains. A total of 500 plates supplemented with 2 mg/liter of ITZ were sent to
10 Spanish tertiary hospitals, and molecular identification and antifungal
susceptibility testing were performed. In addition, the cyp51A gene in those A.
fumigatus strains showing azole resistance was sequenced. A total of 493 isolates
were included in the study. Sixteen strains were isolated from patients with an
infection classified as proven, 104 were isolated from patients with an infection
classified as probable, and 373 were isolated from patients with an infection
classified as colonization. Aspergillus was the most frequent genus isolated, at
80.3%, followed by Scedosporium-Lomentospora (7.9%), Penicillium-Talaromyces
(4.5%), Fusarium (2.6%), and the order Mucorales (1%). Antifungal resistance was
detected in Scedosporium-Lomentospora species, Fusarium, Talaromyces, and
Mucorales Three strains of A. fumigatus sensu stricto were resistant to azoles;
two of them harbored the TR34+L98H mechanism of resistance, and the other one had
no mutations in cyp51A The level of azole resistance in A. fumigatus remains low,
but cryptic species represent over 10% of the isolates and have a broader but
overall higher range of antifungal resistance.
PMID- 29941646
TI - Pharmacokinetics and Comprehensive Analysis of the Tissue Distribution of
Eravacycline in Rabbits.
AB - Eravacycline (7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline or
TP-434) is a novel, fully synthetic broad-spectrum fluorocycline with potent
activity against Gram-positive bacteria, anaerobes, and multidrug-resistant
Enterobacteriaceae We characterized the plasma pharmacokinetics of eravacycline
and conducted a comprehensive analysis of the eravacycline tissue distribution in
rabbits after multiple-day dosing. For single-dose pharmacokinetic analysis,
eravacycline was administered to New Zealand White (NZW) rabbits at 1, 2, 4, 8,
and 10 mg/kg of body weight intravenously (i.v.) once a day (QD) (n = 20). For
multidose pharmacokinetic analysis, eravacycline was administered at 0.5, 1, 2,
and 4 mg/kg i.v. QD (n = 20) for 6 days. Eravacycline concentrations in plasma
and tissues were analyzed by a liquid chromatography-tandem mass spectrometry
assay. Mean areas under the concentration-time curves (AUCs) following a single
eravacycline dose ranged from 5.39 MUg . h/ml to 183.53 MUg . h/ml. Within the
multidose study, mean AUCs ranged from 2.53 MUg . h/ml to 29.89 MUg . h/ml. AUCs
correlated linearly within the dosage range (r = 0.97; P = 0.0001). In the
cardiopulmonary system, the concentrations were the highest in the lung, followed
by the heart > pulmonary alveolar macrophages > bronchoalveolar lavage fluid; for
the intra-abdominal system, the concentrations were the highest in bile, followed
by the liver > gallbladder > spleen > pancreas; for the renal system, the
concentrations were the highest in urine, followed by those in the renal cortex >
renal medulla; for the musculoskeletal tissues, the concentrations were the
highest in muscle psoas, followed by those in the bone marrow > adipose tissue;
for the central nervous system, the concentrations were the highest in cerebrum,
followed by those in the aqueous humor > cerebrospinal fluid > choroid >
vitreous. The prostate and seminal vesicles demonstrated relatively high mean
concentrations. The plasma pharmacokinetic profile of 0.5 to 4 mg/kg in NZW
rabbits yields an exposure comparable to that in humans (1 or 2 mg/kg every 12 h)
and demonstrates target tissue concentrations in most sites.
PMID- 29941647
TI - Leishmania donovani Parasites Are Inhibited by the Benzoxaborole AN2690 Targeting
Leucyl-tRNA Synthetase.
AB - Visceral leishmaniasis is an important public health threat in parts of India. It
is caused by a protozoan parasite, Leishmania donovani Currently available drugs
manifest severe side effects. Hence, there is a need to identify new drug targets
and drugs. Aminoacyl-tRNA synthetases, required for protein synthesis, are known
drug targets for bacterial and fungal pathogens. The aim of the present study was
to obtain essentiality data for Leishmania donovani leucyl-tRNA synthetase
(LdLRS) by gene replacement. Gene replacement studies indicate that this enzyme
plays an essential role in the viability of this pathogenic organism and appears
to be indispensable for its survival in vitro The heterozygous mutant parasites
demonstrated a growth deficit and reduced infectivity in mouse macrophages
compared to the wild-type cells. We also report that Leishmania donovani
recombinant LRS displayed aminoacylation activity and that the protein localized
to both the cytosol and the mitochondrion. A broad-spectrum antifungal, 5-fluoro
1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), was found to inhibit parasite
growth in both the promastigote and amastigote stages in vitro as well as in vivo
in BALB/c mice. This compound exhibited low toxicity to mammalian cells. AN2690
was effective in inhibiting the aminoacylation activity of the recombinant LdLRS.
We provide preliminary chemical validation of LdLRS as a drug target by showing
that AN2690 is an inhibitor both of L. donovani LRS and of L. donovani cell
growth.
PMID- 29941648
TI - Functional Characterization of AbaQ, a Novel Efflux Pump Mediating Quinolone
Resistance in Acinetobacter baumannii.
AB - Acinetobacter baumannii has emerged as an important multidrug-resistant
nosocomial pathogen. In previous work, we identified a putative MFS transporter,
AU097_RS17040, involved in the pathogenicity of A. baumannii (M. Perez-Varela, J.
Corral, J. A. Vallejo, S. Rumbo-Feal, G. Bou, J. Aranda, and J. Barbe, Infect
Immun 85:e00327-17, 2017, https://doi.org/10.1128/IAI.00327-17). In this study,
we analyzed the susceptibility to diverse antimicrobial agents of A. baumannii
cells defective in this transporter, referred to as AbaQ. Our results showed that
AbaQ is mainly involved in the extrusion of quinolone-type drugs in A. baumannii.
PMID- 29941649
TI - Genistein and Ascorbic Acid Reduce Oxidative Stress-Derived DNA Damage Induced by
the Antileishmanial Meglumine Antimoniate.
AB - Meglumine antimoniate (Glucantime) is a pentavalent antimonial used to treat
leishmaniasis, despite its acknowledged toxic effects, such as its ability to
cause oxidative damage to lipids and proteins. Recently, our group demonstrated
that meglumine antimoniate causes oxidative stress-derived DNA damage. Knowing
that antioxidants modulate reactive oxygen species, we evaluated the capacity of
genistein and ascorbic acid for preventing genotoxicity caused by meglumine
antimoniate. For that, mice (n = 5/group) received genistein (via gavage) in
doses of 5, 10, and 20 mg/kg for three consecutive days. After this period, they
were treated with 810 mg/kg meglumine antimoniate via intraperitoneal (i.p.)
route. Furthermore, mice (n = 5/group) simultaneously received ascorbic acid
(i.p.) in doses of 30, 60, and 120 mg/kg and 810 mg/kg meglumine antimoniate. We
also conducted post- and pretreatment assays, in which animals received ascorbic
acid (60 mg/kg) 24 h prior to or after receiving meglumine antimoniate. Genomic
instability and mutagenicity were analyzed through conventional comet assay and
enzymatic assay using formamide pyrimidine DNA glycosylase (Fpg) enzyme, as well
as the micronucleus test, respectively. Meglumine antimoniate induced an increase
in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential
by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic
acid was capable of reducing mutagenic effects in simultaneous treatment as well
as in posttreatment. Therefore, our results demonstrate that both compounds are
efficient in preventing mutations in mammalian cells treated with meglumine
antimoniate.
PMID- 29941650
TI - Combination of Amino Acid Substitutions Leading to CTX-M-15-Mediated Resistance
to the Ceftazidime-Avibactam Combination.
AB - Single amino acid substitutions in the Omega loop of KPC beta-lactamases are
known to lead to resistance to the ceftazidime-avibactam combination. Here, we
investigate this mechanism of resistance in CTX-M enzymes, which are the most
widely spread extended-spectrum beta-lactamases worldwide. Nine single amino acid
polymorphisms were identified in the Omega loop of the 172 CTX-M sequences
present in the Lahey database of beta-lactamases. The corresponding modifications
were introduced in CTX-M-15 by site-directed mutagenesis. None of the nine
substitutions was associated with ceftazidime-avibactam resistance in Escherichia
coli TOP10. However, two substitutions led to 4-fold (P167S) and 16-fold (L169Q)
increases in the MIC of ceftazidime. We determined whether these substitutions
favor the in vitro selection of mutants resistant to ceftazidime-avibactam. The
selection provided mutants for the L169Q substitution but not for the P167S
substitution or for the parental enzyme CTX-M-15. Resistance to the drug
combination (MIC of ceftazidime, 16 MUg/ml in the presence of 4 MUg/ml of
avibactam) resulted from the acquisition of the S130G substitution by CTX-M-15
L169Q. Purified CTX-M-15 with the two substitutions, L169Q and S130G, was only
partially inhibited by avibactam at concentrations as high as 50,000 MUM but
retained ceftazidime hydrolysis activity with partially compensatory decreases in
kcat and Km These results indicate that emergence of resistance to the
ceftazidime-avibactam combination requires more than one mutation in most CTX-M
encoding genes. Acquisition of resistance could be restricted to rare variants
harboring predisposing polymorphisms such as Q at position 169 detected in a
single naturally occurring CTX-M enzyme (CTX-M-93).
PMID- 29941651
TI - TEM-184, a Novel TEM-Derived Extended-Spectrum beta-Lactamase with Enhanced
Activity against Aztreonam.
AB - TEM-184, a novel TEM-derived extended-spectrum beta-lactamase (ESBL), was
isolated from an Escherichia coli ST354 clinical strain. Compared to TEM-1, TEM
184 contains the mutations Q6K, E104K, I127V, R164S, and M182T. Kinetic analysis
of this enzyme revealed extended-spectrum activity against aztreonam in
particular. TEM-184 was also susceptible to inhibitors, including clavulanic
acid, tazobactam, and avibactam.
PMID- 29941652
TI - Population Pharmacokinetics and Dosing Optimization of Azithromycin in Children
with Community-Acquired Pneumonia.
AB - Azithromycin is extensively used in children with community-acquired pneumonia
(CAP). Currently, the intravenous azithromycin is used off-label in children
partly due to lacking of pharmacokinetic data. Our objective was to evaluate the
population pharmacokinetics (PPK) and optimize dose strategy in order to improve
treatment in this distinctive population. This was a prospective, multicenter,
open-labeled pharmacokinetic study. Blood samples were collected from
hospitalized pediatric patients and concentrations were determined by liquid
chromatography-tandem mass spectrometry (LC-MS/MS). PPK analysis was conducted
using NONMEM software. The pharmacokinetic data from 95 pediatric patients (age
range, 2.1 to 11.7 years) were available for analysis. The PPK was best fitted by
a two-compartment model with linear elimination. Covariate analysis verified that
body weight and alanine aminotransferase (ALT) had significant effects on
azithromycin pharmacokinetics, yielding a 24% decrease of clearance in patients
with ALT of >40. Monte Carlo simulation showed that for children with normal
liver function, a loading-dose strategy (a loading dose of 15 mg/kg of body
weight followed by maintenance doses of 10 mg/kg) would achieve the ratio of the
area under free drug plasma concentration-time curve over 24 h (fAUC) to MIC90
(fAUC/MIC) target of 3 h in 53.2% of hypothetical patients, using a normative MIC
susceptibility breakpoint of 2 mg/liter. For children with ALT of >40, the
proposed dose needed to decrease by 15% to achieve comparable exposure. The
corresponding risk of overdose for the recommended dosing regimen was less than
5.8%. In conclusion, the PPK of azithromycin was evaluated in children with CAP
and an optimal dosing regimen was constructed based on developmental
pharmacokinetic-pharmacodynamic modeling and simulation.
PMID- 29941653
TI - Quantification of Cefepime, Meropenem, Piperacillin, and Tazobactam in Human
Plasma Using a Sensitive and Robust Liquid Chromatography-Tandem Mass
Spectrometry Method, Part 2: Stability Evaluation.
AB - Although the stability of beta-lactam antibiotics is a known issue, none of the
previously reported bioanalytical methods had an adequate evaluation of the
stability of these drugs. In the current study, the stability of cefepime,
meropenem, piperacillin, and tazobactam under various conditions was
comprehensively evaluated. The evaluated parameters included stock solution
stability, short-term stability, long-term stability, freeze-thaw stability,
processed sample stability, and whole-blood stability. When stored at -20 degrees
C, the stock solution of meropenem in methanol was stable for up to 3 weeks, and
the stock solutions of cefepime, piperacillin, and tazobactam were stable for up
to 6 weeks. All four antibiotics were stable in human plasma for up to 3 months
when stored at -80 degrees C and were stable in whole blood for up to 4 h at room
temperature. Short-term stability results indicated that all four beta-lactams
were stable at room temperature for 2 h, but substantial degradation was observed
when the plasma samples were stored at room temperature for 24 h, with the
degradation rates for cefepime, meropenem, piperacillin, and tazobactam being
30.1%, 75.6%, 49.0%, and 37.7%, respectively. Because the stability information
is method independent, our stability results can be used as a reference by other
research groups that work with these antibiotics.
PMID- 29941654
TI - Quantification of Cefepime, Meropenem, Piperacillin, and Tazobactam in Human
Plasma Using a Sensitive and Robust Liquid Chromatography-Tandem Mass
Spectrometry Method, Part 1: Assay Development and Validation.
AB - The highly variable pharmacokinetics of beta-lactam antibiotics and beta
lactamase inhibitors poses a significant challenge to clinicians in ensuring
appropriate antibiotic doses in critically ill patients. Therefore, routine
monitoring of plasma concentrations is important for individualization of
antimicrobial therapy. Accordingly, a simple and robust analytical method for the
simultaneous measurement of multiple beta-lactam antibiotics and beta-lactamase
inhibitors is highly desirable to ensure quick decisions on dose adjustments. In
this study, a sensitive, simple, and robust method for the simultaneous
quantification of cefepime, meropenem, piperacillin, and tazobactam in human
plasma was developed and rigorously validated according to FDA guidance. Sample
extraction was accomplished by simple protein precipitation. Chromatographic
separation of analytes was achieved using stepwise gradient elution. Analytes
were monitored using tandem mass spectrometry (MS/MS) with a turbo ion spray
source in positive multiple-reaction-monitoring mode. The calibration curve
ranged from 0.5 to 150 MUg/ml for cefepime, 0.1 to 150 MUg/ml for meropenem and
piperacillin, and 0.25 to 150 MUg/ml for tazobactam. Inter- and intraday
precision and accuracy, sensitivity, selectivity, dilution integrity, matrix
effect, extraction recovery, and hemolysis effect were investigated for all four
analytes, and the results met the acceptance criteria. Compared to other reported
methods, our method is more robust because of the combination of the following
features: (i) a simple sample extraction procedure, (ii) a short sample run time,
(iii) a wide dynamic range, and (iv) the small plasma sample volume needed. Since
our method already covers beta-lactams and a beta-lactamase inhibitor with highly
heterogeneous physicochemical properties, further antibiotic candidates may
easily be incorporated into this multianalyte method.
PMID- 29941655
TI - Iron absorption from oral iron supplements given on consecutive versus alternate
days in iron-depleted women.
PMID- 29941656
TI - Barriers and facilitators to knowledge transfer and exchange in palliative care
research.
AB - In order to ensure the effective transfer of research knowledge to those who can
effect positive changes in practice, models of knowledge transfer and exchange
(KTE) are required. Limited evidence exists as to how palliative care researchers
use existing models to support their practice and to what extent they are
perceived as effective. We set out to identify factors that influence KTE
planning and implementation through semistructured interviews with experienced
palliative care researchers in Ireland. Issues around KTE were drawn out through
thematic analysis. Nine interviews were held with investigators on eight research
projects. Ten themes were identified and categorised as either barriers or
facilitators to KTE. Perceived barriers included inadequate time and funding,
limited institutional capacity, competing priorities, weak communication channels
and negative perceptions of palliative care. Perceived facilitators included
dedicated time and resources, aligned priorities, strong professional networks,
multipronged approach and KTE experience. In order to improve the quality,
acceptability and reach of palliative research, it is vital that researchers
improve their understanding of KTE within the context of palliative care, moving
beyond academic dissemination to achieve research-informed practice by overcoming
barriers to KTE through facilitated action. This study provides an overview of
factors that influence KTE planning and implementation among palliative care
researchers.
PMID- 29941657
TI - Study of occupation and amyotrophic lateral sclerosis in a Danish cohort.
AB - OBJECTIVES: Several manuscripts have proposed associations between amyotrophic
lateral sclerosis (ALS) and occupational toxicant exposures-not to mention
physical activity and trauma/injury. Some have also reported associations in
investigations of specific occupations. Using data from a prospective Danish
cohort study, we investigated the association between employment in certain
industries and ALS diagnosis. METHODS: We identified 1826 ALS cases who were 25
years old or less in 1964 and diagnosed from 1982 to 2013 from the Danish
National Patient Registry then matched 100 population controls to each case based
on birth year and sex. Demographic data were linked to the Danish Pension Fund to
determine occupation history. Conditional logistic regression models were
adjusted for socioeconomic status, marital status and residential location at the
index date. RESULTS: There was an increase in odds of ALS among men who worked in
agriculture, hunting, forestry or fishing (adjusted OR (aOR)=1.21; 95% CI 1.02 to
1.45). There was also a positive association for men employed in construction
(aOR=1.21; 95% CI 1.05 to 1.39). In women, a protective association was seen with
employment in the cleaning industry (aOR=0.69; 95% CI 0.52 to 0.93). CONCLUSIONS:
Our study shows various occupations with exposure to toxicants, such as diesel
exhaust and lead, and strenuous physical activity associated with increased odds
of ALS in men. Future studies should have a particular focus on gathering
detailed information on physical exertion and toxicant exposures specific to
certain job tasks.
PMID- 29941658
TI - Tea Consumption and Longitudinal Change in High-Density Lipoprotein Cholesterol
Concentration in Chinese Adults.
AB - BACKGROUND: The relation between tea consumption and age-related changes in high
density lipoprotein cholesterol (HDL-C) concentrations remains unclear, and
longitudinal human data are limited. The aim of current study was to examine the
relation between tea intake and longitudinal change in HDL-C concentrations.
METHODS AND RESULTS: Baseline (2006) tea consumption was assessed via a
questionnaire, and plasma HDL-C concentrations were measured in 2006, 2008, 2010,
and 2012 among 80 182 individuals (49+/-12 years of age) who did not have
cardiovascular diseases or cancer, or did not use cholesterol-lowering agents
both at baseline (2006) and during the follow-up period (2006-2012). The
associations between baseline tea consumption and rate of change in HDL-C
concentrations were examined using generalized estimating equation models. Tea
consumption was inversely associated with a decreased rate of HDL-C
concentrations (P-trend <0.0001) in the fully adjusted model. The adjusted mean
difference in the HDL-C decreased rate was 0.010 (95% confidence interval, 0.008,
0.012) mmol/L per year for tea consumers versus nonconsumers (never or less than
once/month group). Interactions between tea consumption and age, sex, lifestyle
scores, and metabolic syndrome (all P-interaction <0.0001) were identified. The
associations between greater tea consumption and slower decrease in HDL-C
concentrations were more pronounced in men, individuals aged 60 or older,
individuals with a lower lifestyle score, and individuals with metabolic syndrome
(all P-trend <0.0001). CONCLUSIONS: Tea consumption was associated with slower
age-related decreases in HDL-C concentrations during 6 years of follow-up.
CLINICAL TRIAL REGISTRATION: URL: www.chictr.org. Unique identifier: ChiCTR-TNRC
11001489.
PMID- 29941659
TI - Causal Inference in Cancer Epidemiology: What Is the Role of Mendelian
Randomization?
AB - Observational epidemiologic studies are prone to confounding, measurement error,
and reverse causation, undermining robust causal inference. Mendelian
randomization (MR) uses genetic variants to proxy modifiable exposures to
generate more reliable estimates of the causal effects of these exposures on
diseases and their outcomes. MR has seen widespread adoption within cardio
metabolic epidemiology, but also holds much promise for identifying possible
interventions for cancer prevention and treatment. However, some methodologic
challenges in the implementation of MR are particularly pertinent when applying
this method to cancer etiology and prognosis, including reverse causation arising
from disease latency and selection bias in studies of cancer progression. These
issues must be carefully considered to ensure appropriate design, analysis, and
interpretation of such studies. In this review, we provide an overview of the key
principles and assumptions of MR, focusing on applications of this method to the
study of cancer etiology and prognosis. We summarize recent studies in the cancer
literature that have adopted a MR framework to highlight strengths of this
approach compared with conventional epidemiological studies. Finally, limitations
of MR and recent methodologic developments to address them are discussed, along
with the translational opportunities they present to inform public health and
clinical interventions in cancer. Cancer Epidemiol Biomarkers Prev; 27(9); 995
1010. (c)2018 AACR.
PMID- 29941660
TI - Spatially Resolved Proteome Mapping of Laser Capture Microdissected Tissue with
Automated Sample Transfer to Nanodroplets.
AB - Current mass spectrometry (MS)-based proteomics approaches are ineffective for
mapping protein expression in tissue sections with high spatial resolution
because of the limited overall sensitivity of conventional workflows. Here we
report an integrated and automated method to advance spatially resolved
proteomics by seamlessly coupling laser capture microdissection (LCM) with a
recently developed nanoliter-scale sample preparation system termed nanoPOTS
(Nanodroplet Processing in One pot for Trace Samples). The workflow is enabled by
prepopulating nanowells with DMSO, which serves as a sacrificial capture liquid
for microdissected tissues. The DMSO droplets efficiently collect laser-pressure
catapulted LCM tissues as small as 20 MUm in diameter with success rates >87%. We
also demonstrate that tissue treatment with DMSO can significantly improve
proteome coverage, likely due to its ability to dissolve lipids from tissue and
enhance protein extraction efficiency. The LCM-nanoPOTS platform was able to
identify 180, 695, and 1827 protein groups on average from 12-MUm-thick rat brain
cortex tissue sections having diameters of 50, 100, and 200 MUm, respectively. We
also analyzed 100-MUm-diameter sections corresponding to 10-18 cells from three
different regions of rat brain and comparatively quantified ~1000 proteins,
demonstrating the potential utility for high-resolution spatially resolved
mapping of protein expression in tissues.
PMID- 29941662
TI - Correction: Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved
in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells.
PMID- 29941661
TI - Engrailed homeoprotein blocks degeneration in adult dopaminergic neurons through
LINE-1 repression.
AB - LINE-1 mobile genetic elements have shaped the mammalian genome during evolution.
A minority of them have escaped fossilization which, when activated, can threaten
genome integrity. We report that LINE-1 are expressed in substantia nigra ventral
midbrain dopaminergic neurons, a class of neurons that degenerate in Parkinson's
disease. In Engrailed-1 heterozygotes, these neurons show a progressive
degeneration that starts at 6 weeks of age, coinciding with an increase in LINE-1
expression. Similarly, DNA damage and cell death, induced by an acute oxidative
stress applied to embryonic midbrain neurons in culture or to adult midbrain
dopaminergic neurons in vivo, are accompanied by enhanced LINE-1 expression.
Reduction of LINE-1 activity through (i) direct transcriptional repression by
Engrailed, (ii) a siRNA directed against LINE-1, (iii) the nucleoside analogue
reverse transcriptase inhibitor stavudine, and (iv) viral Piwil1 expression,
protects against oxidative stress in vitro and in vivo We thus propose that LINE
1 overexpression triggers oxidative stress-induced DNA strand breaks and that an
Engrailed adult function is to protect mesencephalic dopaminergic neurons through
the repression of LINE-1 expression.
PMID- 29941664
TI - 'The few cubic centimetres inside your skull': a neurological reading of George
Orwell's Nineteen Eighty-Four.
AB - Nineteen Eighty-Four (1949), George Orwell's political satire on state
surveillance and mind control, was written between 1946 and 1948, at a time when
new thinking in forensic psychiatry coincided with scientific breakthroughs in
neurology to bring questions of criminality, psychotherapy and mental health to
the forefront of the popular imagination. This paper examines how Nineteen Eighty
Four inverts psychiatric paradigms in order to diagnose what Orwell sees as the
madness of totalitarian regimes. It then goes on to place the novel's dystopian
vision of total surveillance and mind control in the context of the neurological
research and brain scanning techniques of the mid-20th century. Not only does
this context provide new insight into the enduring power of Orwell's novel, it
also locates it within a historical moment when technological interventions into
the brain seemed to offer a paradigm of mental health and illness as a simple,
knowable binary. Nineteen Eighty-Four complicates this binary, and deserves to be
acknowledged as an early example of what might be called 'electric shock'
literature, within a mid-20th century canon that includes Harold Pinter's The
Caretaker (1960), Ken Kesey's One Flew Over the Cuckoo's Nest (1962), and Sylvia
Plath's The Bell Jar (1963).
PMID- 29941663
TI - Ligation of the CD44 Glycoform HCELL on Culture-Expanded Human Monocyte-Derived
Dendritic Cells Programs Transendothelial Migration.
AB - The success of dendritic cell (DC)-based immunotherapeutics critically hinges on
the capacity of the vascularly administered cells to enter tissues.
Transendothelial migration (TEM) is dictated by an ordered cascade of
receptor/ligand interactions. In this study, we examined the key molecular
effectors of TEM of human monocyte-derived DCs (mo-DCs) generated by clinically
relevant methods: CD14 selection (CD14-S) and plastic adherence selection (PA-S).
Without chemokine input, CD14-S cells undergo greater TEM than PA-S cells over
TNF-alpha-stimulated HUVECs. TEM of CD14-S mo-DCs is E-selectin/very late Ag-4
(VLA-4) dependent, and engagement of E-selectin ligands activates VLA-4 on CD14-S
mo-DCs but not on PA-S mo-DCs. E-selectin binding glycoforms of P-selectin
glycoprotein ligand-1 (PSGL-1) (i.e., cutaneous lymphocyte Ag [CLA]) and CD44
(i.e., hematopoietic cell E-selectin/L-selectin ligand [HCELL]) are both
expressed on CD14-S mo-DCs, but only CLA is expressed on PA-S mo-DCs. To
elucidate the effect of CD44 or PSGL-1 engagement, mo-DCs were pretreated with
their ligands. Ligation of CD44 on CD14-S mo-DCs triggers VLA-4 activation and
TEM, whereas PSGL-1 ligation does not. HCELL expression on CD14-S mo-DC can be
enforced by cell surface exofucosylation, yielding increased TEM in vitro and
enhanced extravasation into bone marrow in vivo. These findings highlight
structural and functional pleiotropism of CD44 in priming TEM of mo-DCs and
suggest that strategies to enforce HCELL expression may boost TEM of systemically
administered CD14-S mo-DCs.
PMID- 29941665
TI - Essential(ist) medicine: promoting social explanations for racial variation in
biomedical research.
AB - Biomedical research has a long and complicated history as a tool of oppression,
exemplary of the racial science used to legitimise and maintain racial
hierarchies in the USA and abroad. While the explicit racism and racial
inferiority supported by this research has dissipated and modern methods of
inquiry have increased in sophistication and rigor, contemporary biomedical
research continues to essentialise race by distilling racial differences and
disparities in health to an underlying, biogenetic source. Focusing on the
persistence of essentialism in an era of genomic medicine, this paper examines
the deep social origins and social implications of the essentialist viewpoint in
biomedicine and how it relates to the broader construction of social and
scientific knowledge. Invoking Hacking's 'looping effects' as a useful conceptual
tool, I then demonstrate how sociohistorical forces influence scientific and
medical research in producing evidence that favours and legitimises a biological
construction of race. I extend the looping framework to consider a parallel
'louping' process whereby applying a socially rooted meaning to race in
biomedical research results becomes magnified to influence social norms and ideas
about race. As many biomedical researchers are motivated by a desire to eliminate
racial disparities in outcomes, I argue that greater social acuity allows
scientists to avoid individualising and racialising health, challenge
preconceived assumptions about the meaning of racial variation in health and
medicine and thus promote and strengthen a socioenvironmental focus on how to
best improve individuals' and population health. Concluding with a call for
structural competency in biomedical research, I suggest that empowering
scientists to more freely discuss sociostructural factors in their work allows
for the continued use of race in biological and medical research, while social
scientists and medical humanities scholars stand to benefit from seeing their
work imbued with the cultural authority currently granted to biomedicine.
PMID- 29941667
TI - Voltage-Gated Sodium Channels Regulating Action Potential Generation in Itch-,
Nociceptive-, and Low-Threshold Mechanosensitive Cutaneous C-Fibers.
AB - We evaluated the effect of voltage-gated sodium channel 1 (NaV1) blockers in
three nonoverlapping C-fiber subtypes in the mouse skin: chloroquine (CQ)
sensitive C-fibers with high mechanical thresholds-itch C-fibers; second, CQ
insensitive, capsaicin-sensitive C-fibers with high mechanical thresholds
nociceptors; and CQ and capsaicin-insensitive C-fibers with a very low mechanical
threshold-C-LTMs. NaV1-blocking drugs were applied to the nerve terminal
receptive fields using an innervated isolated dorsal mouse skin-nerve preparation
where the drugs are delivered into the skin intra-arterially. We combined these
studies with an analysis of the mRNA expression of the alpha-subunits of NaV1 in
individual dorsal root ganglia neurons labeled from the same region of the skin.
Our results show that virtually all nociceptors and itch C-fibers expressed the
tetrodotoxin (TTX)-resistant channels NaV1.8 and NaV1.9. However, TTX applied
selectively into the skin abolished the action potential firing in response to
mechanical stimulation in 75% of the itch C-fibers, 100% of the nociceptors, and
100% of C-LTMs. NaV1.7 was the most commonly expressed TTX-sensitive NaV1 in all
three C-fiber subtypes innervating the dorsal skin. Selectively blocking NaV1.7
abolished responses in about 40% of itch C-fibers, 65% of nociceptors, but only
20% of C-LTMs. Blocking NaV1.8 alone had no affect on the firing sensitivity of
the C-fibers. However, in itch and nociceptive C-fibers where the activation was
not inhibited with a NaV1.7 blocker, adding the NaV1.8 blocker silenced action
potential discharge.
PMID- 29941666
TI - Chaperone Activity and Dimerization Properties of Hsp90alpha and Hsp90beta in
Glucocorticoid Receptor Activation by the Multiprotein Hsp90/Hsp70-Dependent
Chaperone Machinery.
AB - Several hundred proteins cycle into heterocomplexes with a dimer of the chaperone
heat shock protein 90 (Hsp90), regulating their activity and turnover. There are
two isoforms of Hsp90, Hsp90alpha and Hsp90beta, and their relative chaperone
activities and composition in these client protein*Hsp90 heterocomplexes has not
been determined. Here, we examined the activity of human Hsp90alpha and Hsp90beta
in a purified five-protein chaperone machinery that assembles glucocorticoid
receptor (GR)*Hsp90 heterocomplexes to generate high-affinity steroid-binding
activity. We found that human Hsp90alpha and Hsp90beta have equivalent chaperone
activities, and when mixed together in this assay, they formed only
GR*Hsp90alphaalpha and GR*Hsp90betabeta homodimers and no GR*Hsp90alphabeta
heterodimers. In contrast, GR*Hsp90 heterocomplexes formed in human embryonic
kidney (HEK) cells also contain GR*Hsp90alphabeta heterodimers. The formation of
GR*Hsp90alphabeta heterodimers in HEK cells probably reflects the longer time
permitted for exchange to form Hsp90alphabeta heterodimers in the cell versus in
the cell-free assembly conditions. This purified GR-activating chaperone
machinery can be used to determine how modifications of Hsp90 affect its
chaperone activity. To that effect, we have tested whether the unique
phosphorylation of Hsp90alpha at threonines 5 and 7 that occurs during DNA damage
repair affects its chaperone activity. We showed that the phosphomimetic mutant
Hsp90alpha T5/7D has the same intrinsic chaperone activity as wild-type human
Hsp90alpha in activation of GR steroid-binding activity by the five-protein
machinery, supporting the conclusion that T5/7 phosphorylation does not affect
Hsp90alpha chaperone activity.
PMID- 29941668
TI - Making COPD Self-Management Education Work.
PMID- 29941669
TI - Simulation-Based Evaluation of Mechanical Ventilators.
PMID- 29941670
TI - Asynchrony Between Fact and Dogma.
PMID- 29941671
TI - Asynchrony Between Fact and Dogma-Response.
PMID- 29941673
TI - Mutation in GNE is associated with severe congenital thrombocytopenia.
PMID- 29941674
TI - von Willebrand factor enhances microvesicle-induced vascular leakage and
coagulopathy in mice with traumatic brain injury.
AB - von Willebrand factor (VWF) is an adhesive ligand, and its activity is
proteolytically regulated by the metalloprotease ADAMTS-13 (a disintegrin and
metalloprotease with thrombospondin type 1 repeat 13). An elevated level of
plasma VWF has been widely considered a marker for endothelial cell activation in
trauma and inflammation, but its causal role in these pathological conditions
remains poorly defined. Using a fluid percussion injury mouse model, we
demonstrated that VWF released during acute traumatic brain injury (TBI) was
activated and became microvesicle-bound. The VWF-bound microvesicles promoted
vascular leakage and systemic coagulation. Recombinant ADAMTS-13 given either
before or after TBI reduced the VWF reactivity with minimal influence on VWF
secretion. rADAMTS-13 protected the integrity of endothelial cell barriers and
prevented TBI-induced coagulopathy by enhancing VWF cleavage without impairing
basal hemostasis. Promoting microvesicle clearance by lactadherin had efficacy
similar to that of rADAMTS-13. This study uncovers a novel synergistic action
between VWF and cellular microvesicles in TBI-induced vascular leakage and
coagulopathy and demonstrates protective effects of rADAMTS-13.
PMID- 29941675
TI - The inverse relationship between prostate specific antigen (PSA) and obesity.
AB - Obese men have lower serum prostate-specific antigen (PSA) than comparably aged
lean men, but the underlying mechanism remains unclear. The aim of this study was
to determine the effect of obesity on PSA and the potential contributing
mechanisms. A cohort of 1195 men aged 35 years and over at recruitment, with
demographic, anthropometric (BMI, waist circumference (WC)) and serum hormone
(serum testosterone, estradiol (E2)) PSA and hematology assessments obtained over
two waves was assessed. Men with a history of prostate cancer or missing PSA were
excluded, leaving 970 men for the final analysis. Mixed-effects regressions and
mediation analyses adjusting for hormonal and volumetric factors explore the
potential mechanisms relating obesity to PSA. After adjusting for age, PSA levels
were lower in men with greater WC (P = 0.001). In a multivariable model including
WC, age, E2/testosterone and PlasV as predictors, no statistically significant
associations were observed between with PSA and either WC (P = 0.36) or PlasV (P
= 0.49), while strong associations were observed with both E2/testosterone (P <
0.001) and age (P < 0.001). In the mediation analyses with PlasV as the mediator,
the average causal mediation effect (ACME) explained roughly 20% of the total
effect of WC on PSA (P = 0.31), while when E2/testosterone is a mediator, the
ACME explained roughly 50% of the effect (P < 0.001). Our findings indicate that
lower PSA levels in obese men, as compared to normal weight men, can be explained
both by hormonal changes (elevated E2/testosterone ratio) and hemodilution.
Hormonal factors therefore represent a substantial but underappreciated mediating
pathway.
PMID- 29941677
TI - Hyperglycemia decreases anti-cancer efficiency of Adriamycin via AMPK pathway.
AB - Accumulating clinical evidence indicates that diabetic liver cancer patients are
less sensitive to intra-arterial chemotherapy than non-diabetic cancer patients.
However, the underlying mechanism remains largely uncharacterized. Here, we
report that hyperglycemia inhibits AMPK pathway and subsequently reduces ADR
induced DNA damage, resulting in decreased chemotherapeutic sensitivity of
Adriamycin (ADR). HepG2 and Bel-7402 cells were treated with ADR in various
glucose conditions and then subjected to cell proliferation assay and apoptosis.
The IC50 of ADR greatly increased with the increasing concentration of glucose
(15+/-4nM to 93+/-39nM in HepG2, 78+/-8nM to 1310+/-155nM in Bel-7402). Both FACs
and Western-blot analysis indicated that high concentration of glucose protected
cells from ADR induced apoptosis. Mouse hepatoma H22 xenografts were established
both in db/db diabetic mice and STZ-induced diabetic mice. The inhibitory effect
in tumor growth of ADR was significantly reduced in diabetic mice, which could be
recovered by insulin therapy. Hyperglycemia greatly ameliorated AMPK activation
and H2AXexpression caused by ADR treatment. Pretreatment with Compound C or AMPK
silencing eliminated hyperglycemia reduced cytotoxicity of ADR. However, the
impaired cytotoxicity in hyperglycemia was recovered by treatment with AMPK
activator AICAR. This study indicates that hyperglycemia impairs the
chemotherapeutic sensitivity of ADR by down-regulating AMPK pathway and reducing
ADR induced DNA damage.
PMID- 29941678
TI - Buprenorphine Exposures Among Children and Adolescents Reported to US Poison
Control Centers.
AB - OBJECTIVE: To investigate buprenorphine exposures among children and adolescents
<=19 years old in the United States. METHODS: Data were analyzed from calls to US
poison control centers for 2007-2016 from the National Poison Data System.
RESULTS: From 2007 to 2016, there were 11 275 children and adolescents <=19 years
old exposed to buprenorphine reported to US poison control centers. Most
exposures were among children <6 years old (86.1%), unintentional (89.2%), and to
a single substance (97.3%). For single-substance exposures, children <6 years old
had greater odds of hospital admission and of serious medical outcome than
adolescents 13 to 19 years old. Adolescents accounted for 11.1% of exposures;
77.1% were intentional (including 12.0% suspected suicide), and 27.7% involved
multiple substances. Among adolescents, the odds of hospital admission and a
serious medical outcome were higher for multiple-substance exposures than single
substance exposures. CONCLUSIONS: Buprenorphine is important for the treatment of
opioid use disorder, but pediatric exposure can result in serious adverse
outcomes. Manufacturers should use unit-dose packaging for all buprenorphine
products to help prevent unintentional exposure among young children. Health
providers should inform caregivers of young children about the dangers of
buprenorphine exposure and provide instructions on proper medication storage and
disposal. Adolescents should receive information regarding the risks of substance
abuse and misuse. Suspected suicide accounted for 12% of adolescent exposures,
highlighting the need for access to mental health services for this age group.
PMID- 29941679
TI - The Prenatal Visit.
AB - A pediatric prenatal visit during the third trimester is recommended for all
expectant families as an important first step in establishing a child's medical
home, as recommended by Bright Futures: Guidelines for Health Supervision of
Infants, Children, and Adolescents, Fourth Edition As advocates for children and
their families, pediatricians can support and guide expectant parents in the
prenatal period. Prenatal visits allow general pediatricians to establish a
supportive and trusting relationship with both parents, gather basic information
from expectant parents, offer information and advice regarding the infant, and
may identify psychosocial risks early and high-risk conditions that may require
special care. There are several possible formats for this first visit. The one
used depends on the experience and preference of the parents, the style of the
pediatrician's practice, and pragmatic issues of payment.
PMID- 29941680
TI - When Bad News Isn't Necessarily Bad: Recognizing Provider Bias When Sharing
Unexpected News.
AB - : media-1vid110.1542/5771272502001PEDS-VA_2018-0503Video Abstract.
PMID- 29941676
TI - Detection of a novel, primate-specific 'kill switch' tumor suppression mechanism
that may fundamentally control cancer risk in humans: an unexpected twist in the
basic biology of TP53.
AB - The activation of TP53 is well known to exert tumor suppressive effects. We have
detected a primate-specific adrenal androgen-mediated tumor suppression system in
which circulating DHEAS is converted to DHEA specifically in cells in which TP53
has been inactivated DHEA is an uncompetitive inhibitor of glucose-6-phosphate
dehydrogenase (G6PD), an enzyme indispensable for maintaining reactive oxygen
species within limits survivable by the cell. Uncompetitive inhibition is
otherwise unknown in natural systems because it becomes irreversible in the
presence of high concentrations of substrate and inhibitor. In addition to
primate-specific circulating DHEAS, a unique, primate-specific sequence motif
that disables an activating regulatory site in the glucose-6-phosphatase (G6PC)
promoter was also required to enable function of this previously unrecognized
tumor suppression system. In human somatic cells, loss of TP53 thus triggers
activation of DHEAS transport proteins and steroid sulfatase, which converts
circulating DHEAS into intracellular DHEA, and hexokinase which increases glucose
6-phosphate substrate concentration. The triggering of these enzymes in the TP53
affected cell combines with the primate-specific G6PC promoter sequence motif
that enables G6P substrate accumulation, driving uncompetitive inhibition of G6PD
to irreversibility and ROS-mediated cell death. By this catastrophic 'kill
switch' mechanism, TP53 mutations are effectively prevented from initiating
tumorigenesis in the somatic cells of humans, the primate with the highest peak
levels of circulating DHEAS. TP53 mutations in human tumors therefore represent
fossils of kill switch failure resulting from an age-related decline in
circulating DHEAS, a potentially reversible artifact of hominid evolution.
PMID- 29941682
TI - Editorial.
PMID- 29941683
TI - Prevalence of maternal immunisation with seasonal influenza vaccine in Hong Kong.
PMID- 29941685
TI - Prevention and treatment of swine-origin influenza virus with interferon: an in
vivo and ex vivo study.
PMID- 29941684
TI - The role of balanced haemagglutinin-neuraminidase activity in the genesis of
transmissible neuraminidase inhibitor-resistant variants in seasonal and novel
pandemic influenza A H1N1 viruses.
PMID- 29941687
TI - Gene regulatory function and cellular partners of SARS-associated coronavirus
nucleocapsid protein.
PMID- 29941686
TI - Metagenomics of tuberculosis infection in Hong Kong.
PMID- 29941688
TI - Mechanistic study on the assembly and release of lentiviral particles pseudotyped
with haemagglutinin of highly pathogenic avian influenza H5N1 viruses:
implications for strain-specific pseudotype development.
PMID- 29941689
TI - Screening of aqueous and organic extracts from a variety of fungi for their
ability to antagonise the pathogenic yeast Candida albicans.
PMID- 29941690
TI - Functional analysis of apoptosis-inducing factor in the human fungal pathogen
Candida albicans.
PMID- 29941691
TI - Identification of antifungal molecules from novel probiotic Lactobacillus
bacteria for control of Candida infection.
PMID- 29941692
TI - Antimicrobial activity of cathelicidin peptides and defensin against oral yeast
and bacteria.
PMID- 29941693
TI - Event-specific risk factors predicting unprotected anal intercourse among Hong
Kong men who have sex with men: a case-crossover study.
PMID- 29941694
TI - Molecular dissection of dengue virus egress: involvement of the class II ARF
small GTPase.
PMID- 29941695
TI - Inhibition of RIG-I-dependent innate immunity by herpes simplex virus type I Us11
protein.
PMID- 29941696
TI - Bone Mineral Content and Density in Indian Children with Congenital Adrenal
Hyperplasia.
AB - OBJECTIVE: To study the bone mineral content and density in children with
congenital adrenal hyperplasia (CAH). METHODS: 35 children with congenital
adrenal hyperplasia and 35 healthy controls. Bone mineral content and density
were studied by Dual Energy X-ray absorptiometry. RESULTS: The mean (SD) of
lumbar spine bone mineral density (g/cm2) [0.590 (0.100) vs 0.589 (0.088)
(P=0.97)], total Body less head bone mineral density (g/cm2) [0.536 (0.090) vs
0.548 (0.111) (P=0.64)], lumbar spine bone mineral content (g) [29.85 (27.63) vs
31.03 (29.19) (P=0.86)], and total body less head bone mineral content (g)
[254.27 (281.25) vs 273.07 (330.71) (P=0.79)] were not different between children
with CAH and controls, respectively. CONCLUSIONS: Bone mineral density and
content in children with congenital adrenal hyperplasia are maintained in the
normal range.
PMID- 29941697
TI - Management of Childhood Functional Constipation: Consensus Practice Guidelines of
Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition and
Pediatric Gastroenterology Chapter of Indian Academy of Pediatrics.
AB - JUSTIFICATION: Management practices of functional constipation are far from
satisfactory in developing countries like India; available guidelines do not
comprehensively address the problems pertinent to our country. PROCESS: A
questionnaire-based survey was conducted among selected practising pediatricians
and pediatric gastroenterologists in India, and the respondents agreed on the
need for an Indian guideline on the topic. A group of experts were invited to
present the published literature under 12 different headings, and a consensus was
developed to formulate the practice guidelines, keeping in view the needs in
Indian children. OBJECTIVE: To formulate practice guidelines for the management
of childhood functional constipation that are relevant to Indian children.
RECOMMENDATIONS: Functional constipation should be diagnosed only in the absence
of red flags on history and examination. Those with impaction and/or retentive
incontinence should be disimpacted with polyethylene glycol (hospital or home
based). Osmotic laxatives (polyethylene glycol more than 1 year of age and
lactulose/lactitol less than 1 year of age) are the first line of maintenance
therapy. Stimulant laxatives should be reserved only for rescue therapy.
Combination therapies of two osmotics, two stimulants or two classes of laxatives
are not recommended. Laxatives as maintenance therapy should be given for a
prolonged period and should be tapered off gradually, only after a successful
outcome. Essential components of therapy for a successful outcome include
counselling, dietary changes, toilet-training and regular follow-up.
PMID- 29941698
TI - Evaluating Neonates With Antenatal Hyderonephrosis Using a Standard Potocol: A
Audit of Hospital Records.
AB - AIMS: To audit the extent of evaluation of neonates with antenatal
hydronephrosis. METHODS: Records of all neonates with antenatal hydronephrosis
between January 2013 and December 2016 were audited to look for patient factors
and investigation results. RESULTS: 290 records were evaluated, 93 (32%) of which
had abnormalities detected on voiding cystourethrogram. In the presence of
hydroureter, 65% had an abnormality while in the absence of only 11% were
abnormal. In the presence of pelvis >20 mm, 93% had abnormal diuretic renogram,
while with pelvis <20 mm, only 1.5% were abnormal (P=0.001). Numbers needed to
harm calculation revealed 1 in 2 patients would receive an unnecessary voiding
cystourethrogram in the absence of hydroureter, and unnecessary diuretic renogram
when pelvis <20 mm. CONCLUSIONS: While evaluating neonates with antenatal
hydronephrosis invasive tests can be limited, if evaluation is guided by
ultrasonographic criteria.
PMID- 29941699
TI - Risk Factors for Microbiologically-documented Infections, Mortality and Prolonged
Hospital Stay in Children with Febrile Neutropenia.
AB - OBJECTIVE: To analyze the risk factors for microbiologically documented
infection, mortality and hospital stay more than 5 days in children with febrile
neutropenia. DESIGN: Cross-sectional study (July 2013-September 2014). SETTING:
Government-run, tertiary-care, university hospital in Chandigarh, Northern India.
PARTICIPANTS: 414 episodes in 264 children aged <12 years, not undergoing stem
cell transplantation. OUTCOME MEASURES: Predictors for 'high-risk' febrile
neutropenia. RESULTS: Microbiologically-documented infections were observed in 82
children (19.8%); bacterial 14.2%, fungal 4.3%, polymicrobial 9.7%. Complications
were documented in 109 (26%) children. 43 (10.3%) died: 8 due to fungal and 35
due to bacterial sepsis. Children admitted within 7 days of the last chemotherapy
(P<0.01) and having a non-upper respiratory focus of infection (P<0.02) were at
risk of developing microbiologically-documented infections and death. Platelet
count <20000/uL (P=0.03) was an additional predictor for microbiologically
documented infections, while albumin <2.5 g/dL (P=0.04) and C-reactive protein
>90 mg/L (P=0.02) were risk factors predicting mortality. The median (IQR)
duration of hospital stay was 5 (3,8) days. Hospital stay <5 days was seen in 144
(35%) children. Children with acute myeloid leukaemia (P<0.01) and admitted
within 7 days of chemotherapy (P=0.02) were likely to have a prolonged hospital
stay >5 days. CONCLUSIONS: Febrile neutropenic children admitted within 7 days of
completion of chemotherapy, those with a non-upper respiratory focus of
infection, CRP >90 mg/dL, platelet <20000/uL and albumin <2.5 g/dL need to be
considered as 'high risk' for complications and mortality.
PMID- 29941700
TI - Infantile Colic: An Update.
AB - CONTEXT: Infantile colic is self-limiting condition but it can be a cause of
anxiety for parents and challenge for doctors. The challenge for the doctors lies
in correct identification of the condition and appropriate management. The
objective of this review article is to summarize the pathophysiology, treatment
options and outcome in infantile colic so that clinicians can have a fair idea
about the condition, recent updates and future prospective. EVIDENCE: A search of
The Cochrane Library, PubMed, Google Scholar was made using the key words "Infant
colic", Infantile colic", "excessive crying in infants". All the materials were
analyzed and summarized. RESULTS: At present infantile colic is an area of
clinical research both in terms of etiology and treatment. Various etiological
theories have been proposed but none of them are strong enough to completely
describe the condition. Various treatment agents are being tried for colic like
counseling and behavioral modification, dietary modification, lactase and
probiotic supplementation, pain relieving agents, and chiropathy. Proper
counseling of the parents is the first line of management at present. Simethicone
has no role in decreasing the symptoms of colic and Dicyclomine is not
recommended in children younger than six months. No specific recommendations have
been made on the use of pain relieving agents and manipulative therapies in
colic. At present strong evidence is lacking regarding the use of probiotics,
lactase supplementation and dietary modification. CONCLUSION: Counseling of
parents about the benign nature of the condition is considered first line for now
until an effective treatment is established. Other treatment options are
prescribed on a case-based manner and parental perception of the condition.
PMID- 29941701
TI - Incidence and Risk Factors for Hypertension During Childhood Acute Lymphoblastic
Leukemia Therapy.
AB - OBJECTIVE: To determine the incidence of hypertension among children during the
induction and re-induction phases of acute lymphoblastic leukemia (ALL) therapy
and association with possible risk factors. METHODS: A retrospective analysis of
208 consecutive pediatric (age <18 y) ALL patients, treated per BFM-95 protocol
between January 2009 and December 2013. Data were analyzed to determine the
incidence of hypertension and risk factors for its development. RESULTS:
Incidence of hypertension requiring antihypertensive medication, was 29% (61/208)
during induction and 17% (33/198) during re-induction (P=0.003). Median (range)
age of patients developing hypertension was 4 y (4 mo to 8 y). Age <10 y and
presence of constipation were independently predictive of hypertension by
multivariate analysis. CONCLUSIONS: The present study reports a high incidence of
hypertension among children undergoing ALL induction therapy.
PMID- 29941702
TI - Serum Hepcidin Levels in Children with Beta Thalassemia Major.
AB - The mean (SD) serum hepcidin levels in 40 children with thalassemia [15.8 (2.9)
ng/mL] were comparable to those seen in 40 healthy controls [15.1 (3.0) ng/mL
(P=0.3)]. The hepcidin/ferritin ratio in thalassemic children was significantly
lower (P<0.001) suggesting that hepcidin levels were not increased in proportion
to the iron overload.
PMID- 29941703
TI - Neutrophil Extracellular Traps in Autoimmune Diseases.
PMID- 29941704
TI - Clinical Relevance of Autoantibodies against Interleukin-2 in Patients with
Systemic Lupus Erythematosus.
AB - Background: Increased serum autoantibodies against interleukin-2 (anti-IL-2
autoantibodies) were reported in patients with systemic lupus erythematosus (SLE)
and in patients receiving IL-2 therapy. This study aimed to explore the clinical
relevance of serum anti-IL-2 autoantibodies and the interactions between low-dose
IL-2 therapy and serum anti-IL-2 autoantibodies. Methods: Serum samples were
collected from 152 SLE patients and 100 age- and gender-matched healthy controls
(HCs). Among them, 75 SLE patients were followed up for 10 weeks, and all of them
were treated with corticosteroids, antimalarials, and/or immunosuppressants.
Forty-six out of the 75 SLE patients received low-dose IL-2 therapy additionally.
Clinical and laboratory parameters were collected at baseline and week 10. Serum
anti-IL-2 autoantibodies were determined by enzyme-linked immunosorbent assay.
Results: Compared with HCs, median levels and positive rates of serum anti-IL-2
autoantibodies were higher in SLE patients (32.58 [23.63, 45.23] arbitrary unit
[AU] vs. 37.54 [27.88, 60.74] AU, P = 0.006, and 5.0% vs. 18.4%, P = 0.002,
respectively). Compared to those without the corresponding disorders, serum anti
IL-2 autoantibody was increased in patients with alopecia (49.79 [36.06, 64.95]
AU vs. 35.06 [25.40, 58.46] AU, P = 0.033), but it was decreased in those with
lupus nephritis (31.71 [22.60, 43.25] AU vs. 44.15 [31.43, 68.52] AU, P = 0.001).
Moreover, serum anti-IL-2 autoantibody was positively correlated with serum IgA
(r = 0.229, P = 0.005), total IgG (r = 0.327, P < 0.001), and total IgM (r =
0.164, P = 0.050). Treatment with exogenous IL-2 was not significantly associated
with serum anti-IL-2 autoantibody. In addition, no significant difference was
found in serum anti-IL-2 autoantibody between responders and nonresponders to low
dose IL-2 therapy. Conclusions: Serum anti-IL-2 autoantibody was increased and
associated with disease severity in SLE. Exogenous low-dose IL-2 did not
significantly induce anti-IL-2 autoantibody production.
PMID- 29941705
TI - Increased Macroautophagy in Interferon-Gamma-Producing T Cells from Patients with
Newly Diagnosed Systemic Lupus Erythematosus.
AB - Background: Imbalance of interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL
17 producing by T cells is confirmed to contribute to the pathogenesis of
systemic lupus erythematosus (SLE). Autophagy is now emerging as a core player in
the development and the function of the immune system. Therefore, we investigated
the autophagic behavior in IFN-gamma-, IL-4-, and IL-17-producing T cells from
patients with SLE. Methods: Thirty patients with SLE and 25 healthy controls
matched for gender and age were recruited between September 2016 and May 2017.
The autophagic levels in IFN-gamma+ T cells, IL-4+ T cells, and IL-17+ T cells
from patients with newly diagnosed SLE and healthy controls were measured using
flow cytometry. The plasma levels of IFN-gamma were determined by enzyme-linked
immunosorbent assay in SLE patients and healthy controls. Unpaired t-tests and
the nonparametric Mann-Whitney U-test were used to compare data from patients
with SLE and controls. Spearman's rank correlation coefficient was applied for
calculation of the correlation between parallel variables in single samples.
Results: Our results showed increased percentage of autophagy in IFN-gamma+ T
cells from patients with SLE and healthy controls ([8.07 +/- 2.72]% vs. [3.76 +/-
1.67]%, t = 5.184, P < 0.001), but not in IL-4+ T cells or IL-17+ T cells (P >
0.05) as compared to healthy donors. Moreover, the plasma levels of IFN-gamma in
SLE patients were significantly higher than those in healthy controls ([68.9 +/-
29.1] pg/ml vs. [24.7 +/- 17.6] pg/ml, t = 5.430, P < 0.001). Moreover, in SLE
patients, the percentage of autophagy in IFN-gamma+ T cells was positively
correlated with the plasma levels of IFN-gamma (r = 0.344, P = 0.046), as well as
the disease activity of patients with SLE (r = 0.379, P = 0.039). Conclusion: The
results indicate that autophagy in IFN-gamma+ T cells from SLE patients is
activated, which might contribute to the persistence of T cells producing IFN
gamma, such as Th1 cells, and consequently result in the high plasma levels of
IFN-gamma, and then enhance the disease activity of SLE.
PMID- 29941706
TI - Mycophenolic Acid Synergizing with Lipopolysaccharide to Induce Interleukin-1beta
Release via Activation of Caspase-1.
AB - Background: The previous study showed that mycophenolic acid (MPA) synergizing
with lipopolysaccharide (LPS) promoted interleukin (IL)-1beta release, but the
mechanism is unclear. This study aimed to investigate the mechanism of MPA
synergizing with LPS to induce IL-1beta release. Methods: Undiluted human blood
cells, THP-1 human myeloid leukemia mononuclear cells (THP-1) cells, or monocytes
were stimulated with LPS and treated with or without MPA, and the supernatant IL
1beta was detected by enzyme-linked immunosorbent assay. The mRNA levels of IL
1beta were detected by real-time quantitative polymerase chain reaction. The
intracellular protein levels of nuclear factor kappa B (NF-kappaB) phospho-p65 (p
p65), precursor interleukin-1beta (pro-IL-1beta), NOD-like receptor pyrin domain
containing-3 (NLRP3), and cysteine aspartic acid-specific protease-1 (caspase-1)
p20 in THP-1 cell were measured by Western blot. Results: The MPA alone failed to
induce IL-1beta, whereas MPA synergized with LPS to increase IL-1beta in a dose
dependent manner (685.00 +/- 20.00 pg/ml in LPS + 5 MUmol/L MPA group, P = 0.035;
742.00 +/- 31.58 pg/ml in LPS + 25 MUmol/L MPA group, P = 0.017; 1000.00 +/-
65.59 pg/ml in LPS + 75 MUmol/L MPA group, P = 0.024; versus 408.00 +/- 35.50
pg/ml in LPS group). MPA alone has no effect on the IL-1beta mRNA expression, LPS
induced the expression of IL-1beta mRNA 2761 fold, and LPS + MPA increased the IL
1beta expression 3018 fold, which had the same effect with LPS group (P = 0.834).
MPA did not affect the intracellular NF-kappaB p-p65 and pro-IL-1beta protein
levels but activated NLRP3 inflammasome. Ac-YVAD-cmk blocked the activation of
caspase-1 and subsequently attenuated IL-1beta secretion (181.00 +/- 45.24 pg/ml
in LPS + MPA + YVAD group vs. 588.00 +/- 41.99 pg/ml in LPS + MPA group, P =
0.014). Conclusions: Taken together, MPA synergized with LPS to induce IL-1beta
release via the activation of caspase-1, rather than the enhanced production of
pro-IL-1beta. These findings suggested that patients immunosuppressed with
mycophenolate mofetil may have overly activated caspase-1 during infection, which
might contribute to a more sensitive host defense response to invading germs.
PMID- 29941707
TI - Pelvic Exenteration for Recurrent and Persistent Cervical Cancer.
AB - Background: Pelvic exenteration (PE) for primary and recurrent cervical cancer
has resulted in favorable survival outcomes, but there are controversies about
specific prognosis factors, and up to now, there have been no published reports
from China. This study aimed to share our experiences of PE, which were performed
in a single institution. Methods: From January 2009 to January 2016, 38 patients
with recurrent or persistent cervical cancer were included in the study, and they
were followed up until January 2017. Epidemiological and clinicopathological
characteristics of patients were compared for survival outcomes in univariate and
Cox hazard regression analysis. Results: There were thirty-one and seven patients
with recurrent and persistent cervical cancer, respectively. The median age of
patients was 45 years (range 29-65 years). Total, anterior, and posterior PE
consisted of 52.6%, 28.9%, and 18.4% of cases, respectively. Early and late
complications occurred in 21 (55.3%) patients and 15 (39.5%) patients,
respectively. Two (5.3%) patients died due to complications related to surgeries
within 3 months after PE. The median overall survival (OS) and disease-free
survival (DFS) were 28.5 months (range 9-96 months) and 23 months (range 4-96
months), respectively, and 5-year OS and DFS were 48% and 40%, respectively. Cox
hazard regression analysis showed that, the margin status of the incision and
mesorectal lymph node status were independent risk factors for OS and DFS.
Conclusion: In our patients with recurrent and persistent cervical cancer, the
practice of PE might achieve favorable survival outcomes. Trial Registration:
ClinicalTrials.gov, NCT03291275;
https://clinicaltrials.gov/ct2/show/NCT03291275?term=NCT03291275&rank=1.
PMID- 29941708
TI - A Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial of Qi-Zhi-Wei
Tong Granules on Postprandial Distress Syndrome-Predominant Functional Dyspepsia.
AB - Background: Functional dyspepsia (FD) is a common upper gastrointestinal disorder
worldwide, but the current treatments for FD are still unsatisfactory. The aims
of this study were to investigate the efficacy and safety of Qi-Zhi-Wei-Tong
granules in patients with postprandial distress syndrome (PDS)-predominant FD.
Methods: The study was conducted as a randomized, double-blinded, multicenter,
placebo-controlled design in 197 patients with PDS. All participants received
placebo treatment for 1 week. Patients whose total symptom score decreased by
<50% after the placebo treatment were recruited into the 4-week treatment period,
in which they were randomly assigned to be treated with either Qi-Zhi-Wei-Tong
granules or placebo. The patients were then followed for 2 weeks without any
treatment. Dyspeptic symptoms were scored at weeks 2 and 4 during the random
treatment period and 2 weeks after the treatment. Anxiety and depression symptoms
were also scored and compared. Results: (1) The total effective rates in the Qi
Zhi-Wei-Tong granules group at weeks 2 and 4 during the random treatment period
and 2 weeks after treatment were all significantly higher than those in the
placebo group (38.82% vs. 8.75%, P < 0.001; 69.14% vs. 16.25%, P < 0.001; 77.65%
vs. 21.25%, P < 0.001). (2) The total dyspeptic symptoms scores in the Qi-Zhi-Wei
Tong granules group at weeks 2 and 4 and 2 weeks after treatment were
significantly lower than those in the placebo group. (3) The severity and
frequency of each dyspeptic symptom at weeks 2 and 4 and the follow-up period
were all significantly lower than those in the placebo group. (4) The anxiety
scores in the Qi-Zhi-Wei-Tong granules group were significantly lower than those
in the placebo group. (5) Qi-Zhi-Wei-Tong granules did not have more adverse
effects than the placebo. Conclusion: Qi-Zhi-Wei-Tong granules offer significant
symptomatic improvement in PDS with no more adverse effects than placebo. Trial
Registration: https://clinicaltrials.gov/, NCT02460601.
PMID- 29941709
TI - Comparison of Vaginal Gel and Intramuscular Progesterone for In vitro
Fertilization and Embryo Transfer with Gonadotropin-Releasing Hormone Antagonist
Protocol.
AB - Background: Luteal support is a key to patients undergoing in vitro fertilization
and embryo transfer (IVF-ET) with gonadotropin-releasing hormone (GnRH)
antagonist protocol. This study aimed to compare the effect between vaginal
progesterone (VP) and intramuscular progesterone (IMP) with GnRH-antagonist
protocol after IVF-ET. Methods: A total of 1760 patients (18 years <= age <=35
years) undergoing IVF-ET with GnRH-antagonist protocol were studied
retrospectively between September 2014 and August 2015 in Peking University Third
Hospital. In the patients, 1341 patients received VP (VP group) and 419 patients
received IMP (IMP group) as luteal support. We compared clinical outcomes between
these two groups. The primary objective of the study was the live birth rate.
Measurement data between the two groups were conducted using independent samples
t-test. The variables in line with non-normal distribution were expressed as
median (p25 and p75) and were compared using nonparametric Mann-Whitney U-test.
Results: Live birth rate in VP group was 38.55%, significantly higher than that
in the IMP group, which was 30.79% (chi2 = 8.287, P = 0.004). The clinical
intrauterine pregnancy rate and implantation rate in VP group were also
significantly higher than those in the IMP group (clinical intrauterine pregnancy
rate 47.35% vs. 41.29%, chi2 = 4.727, P = 0.030; implantation rate 30.99% vs.
25.26%, chi2 = 14.546, P < 0.001). Any statistically significant differences in
ectopic pregnancy and abortion rates between two groups were not observed.
Conclusion: : Luteal support with VP had better clinical outcomes for young women
undergoing IVF-ET with GnRH-antagonist protocol.
PMID- 29941710
TI - A Novel Mutation of Mitochondrial T14709C Causes Myoclonic Epilepsy with Ragged
Red Fibers Syndrome in a Chinese Patient.
AB - Background: Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is
characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged
red fibers (RRFs) in the muscle. T-to-C transition at nucleotide position 14709
in the mitochondrial tRNA glutamic acid (tRNAGlu) gene has previously been
associated with maternally inherited diabetes and deafness. However, the
association between MERRF and mitochondrial T14709C mutation (m.T14709C) has
never been reported before. Methods: Clinical information of a 17-year-old
patient was collected; muscle biopsy and next-generation sequencing (NGS) of
whole mitochondrial and neuromuscular disease panel were then conducted. Finally,
sanger sequencing was carried out to confirm the mutations. Results: The patient
presented a typical MERRF phenotype with muscle weakness, epileptic seizure,
clonic episodes, cerebellar ataxia, and spinal scoliosis. Muscle biopsy showed
RRFs which indicated abnormal mitochondrial functions. NGS of whole mitochondrial
gene revealed m.T14709C mutation, confirmed by Sanger sequencing. Conclusion: We
present a sporadic patient with typical MERRF presentation carrying the mutation
of m.T14709C, which expanded the spectrum of m.T14709C.
PMID- 29941711
TI - Identification of a Novel Homozygous Splice-Site Mutation in SCARB2 that Causes
Progressive Myoclonus Epilepsy with or without Renal Failure.
AB - Background: Progressive myoclonus epilepsies (PMEs) comprise a group of rare
genetic disorders characterized by action myoclonus, epileptic seizures, and
ataxia with progressive neurologic decline. Due to clinical and genetic
heterogeneity of PMEs, it is difficult to decide which genes are affected. The
aim of this study was to report an action myoclonus with or without renal failure
syndrome (EPM4) family and summarize the clinical and genetic characteristics of
all reported EPM4 patients. Methods: In the present study, targeted next
generation sequencing (NGS) was applied to screen causative genes in a Chinese
PME family. The candidate variant was further confirmed by cosegregation analysis
and further functional analysis, including the reverse transcription polymerase
chain reaction and Western blot of the proband's muscle. Moreover, literature
data on the clinical and mutational features of all reported EPM4 patients were
reviewed. Results: The gene analysis revealed a novel homozygous splicing
mutation (c.995-1G>A) of the SCARB2 gene in two brothers. Further functional
analysis revealed that this mutation led to loss function of the SCARB2 protein.
The classification of the candidate variant, according to the American College of
Medical Genetics and Genomics standards and guidelines and functional analysis,
was pathogenic. Therefore, these two brothers were finally diagnostically
confirmed as EPM4. Conclusions: These present results suggest the potential for
targeted NGS to conduct a more rapid and precise diagnosis for PME patients. A
literature review revealed that mutations in the different functional domains of
SCARB2 appear to be associated with the phenotype of EPM4.
PMID- 29941712
TI - Inductively Coupled Plasma Mass Spectrometry as a Reference Method to Evaluate
Serum Calcium Measurement Bias and the Commutability of Processed Materials
during Routine Measurements.
AB - Background: Measuring total serum calcium is important for the diagnosis of
diseases. Currently, results from commercial kits for calcium measurement are
variable. Generally, the performance of serum calcium measurements is monitored
by external quality assessment (EQA) or proficiency testing schemes. However, the
commutability of the EQA samples and calibrators is often unknown, which limits
the effectiveness of EQA schemes. The aim of this study was to evaluate the bias
of serum calcium measurements and the commutability of processed materials.
Methods: Inductively coupled plasma mass spectrometry was applied as a
comparative method, and 14 routine methods were chosen as test methods. Forty
eight serum samples from individual patients and 25 processed materials were
quantified. A scatter plot was generated from patient samples, and 95% prediction
intervals were calculated to evaluate the commutability of the processed
materials and measurement bias at three concentration levels was used to
determine the accuracy of routine assays. Results: All assays showed high
precision (total coefficient of variation [CV] <2.26%) and correlation
coefficients (r > 0.99). For all assays, the mean bias for the 48 patient samples
ranged from -0.13 mmol/L to 0.00 mmol/L (-5.61-0.01%), and the ranges for the
three concentrations were -0.10-0.04 mmol/L (-5.71-2.35%), -0.14--0.01 mmol/L (
5.80--0.30%), and -0.19-0.04 mmol/L (-6.24-1.22%). The EQA samples, calibrators,
and animal sera exhibited matrix effects in some assays; human serum pools were
commutable in all assays; certificate reference materials were commutable in most
assays, and only GBW09152 exhibited a matrix effect in one assay; and aqueous
reference materials exhibited matrix effects in most assays. Conclusions: Biases
for most assays were within the acceptable range, although the accuracy of some
assays needs improvement. Human serum pools prepared from patient samples were
commutable, and the other tested materials exhibited a matrix effect.
PMID- 29941713
TI - Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth
Nanoparticles in Mice.
AB - Background: Nanotechnology is emerging as a promising tool to perform noninvasive
therapy and optical imaging. However, nanomedicine may pose a potential risk of
toxicity during in vivo applications. In this study, we aimed to investigate the
potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.
Methods: We synthesized RENPs through a typical co-precipitation method.
Institute of Cancer Research (ICR) mice were randomly divided into seven groups
including a control group and six experimental groups (10 mice per group). ICR
mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0,
and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in
mice, magnetic resonance imaging (MRI) was performed to assess their uptake in
mice. In addition, hematological and biochemical analyses were conducted to
evaluate any impairment in the organ functions of ICR mice. The analysis of
variance (ANOVA) followed by a one-way ANOVA test was used in this study. A
repeated measures' analysis was used to determine any significant differences in
white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA)
levels at different evaluation times in each group. Results: We demonstrated the
successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their
physical properties were characterized by transmission electron microscopy and a
980 nm laser diode. Results of MRI study revealed the distribution and
circulation of the RENPs in the liver. In addition, the hematological analysis
found an increase of WBCs to (8.69 +/- 0.85) * 109/L at the 28th day, which is
indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF4:Er
nanoparticles. Furthermore, the biochemical analysis indicated increased levels
of ALT ([64.20 +/- 15.50] U/L) and CREA ([27.80 +/- 3.56] MUmol/L) at the 28th
day, particularly those injected with 1.5 mg/kg NaYbF4:Er nanoparticles. These
results suggested the physiological and pathological damage caused by these
nanoparticles to the organs and tissues of mice, especially to liver and kidney.
Conclusion: The use of bare RENPs may cause possible hepatotoxicity and
nephritictoxicity in mice.
PMID- 29941714
TI - Genistein Improves Liver Damage in Male Mice Exposed to Morphine.
AB - Background: Morphine is commonly used to treat severe pain. This substance is
significantly metabolized in the liver and causes disturbing effects. Genistein
is an isoflavone and has antioxidant properties. The aim of this study was to
evaluate the effects of genistein against morphine damages on mouse liver.
Methods: Between May 2017 and March 2018, 48 male mice were divided into six
groups (n = 8 in each group). Various doses of genistein (25 and 50 mg/kg) and
morphine plus genistein (25 and 50 mg/kg) were administered intraperitoneally to
48 male mice for 20 consequent days. Aspartate aminotransferase (AST), alanine
aminotransferase (ALT), alkaline phosphatase (ALP), serum nitric oxide (NO)
levels, liver weight, and the diameter of hepatocytes and central hepatic vein
were studied and compared using one-way analysis of variance. Results: Morphine
administration significantly increased the mean diameter of the central hepatic
vein (22.76 +/- 1.9 MUm vs. 15.04 +/- 0.60 MUm, chi2 = 21.814, P = 0.001) and
hepatocytes (3.03 +/- 0.10 MUm vs. 1.10 +/- 0.05 MUm, chi2 = 9.873, P = 0.001)
respectively, blood serum NO level (38.00% +/- 2.09% vs. 18.72% +/- 4.40%, chi2 =
20.404, P < 0.001), liver enzyme level (AST: 111.80 +/- 5.10 ng/ml vs. 81.93 +/-
2.20 ng/ml, chi2 = 32.201, P < 0.0001; ALT: 45.14 +/- 4.10 ng/ml vs. 35.49 +/-
2.50 ng/ml, chi2 = 18.203, P < 0.0001; and ALP: 3.28 +/- 0.20 ng/ml vs. 2.14 +/-
0.10, chi2 = 5.04, P < 0.0001, respectively), and decreased liver weight (18.50
+/- 0.90 g vs. 27.15 +/- 0.50 g, chi2 = 22.415, P = 0.001) compared to saline
group (0.535-0.750, P < 0.0001). However, administration of genistein plus
morphine significantly enhanced liver weight (25 mg/kg: 21.15 +/- 2.13 g vs.
18.50 +/- 0.90 g, chi2 = 19.251, P < 0.0001; 50 mg/kg: 21.20 +/- 1.00 g vs. 18.5
+/- 0.9 g, chi2 = 19.502, P < 0.0001, respectively) and reduced the mean diameter
of hepatocyte (25 mg/kg: 2.17 +/- 0.30 MUm vs. 3.03 +/- 0.10 MUm, chi2 = 22.780,
P = 0.001; 50 mg/kg: 2.01 +/- 0.20 MUm vs. 3.03 +/- 0.10 MUm chi2 = 7.120, P =
0.001, respectively), central hepatic vein (25 mg/kg: 19.53 +/- 1.00 MUm vs.
22.76 +/- 1.90 MUm, chi2 = 20.681, P = 0.001; 50 mg/kg: 19.44 +/- 1.20 MUm vs.
22.76 +/- 1.90 MUm, chi2 = 18.451, P = 0.001, respectively), AST (25 mg/kg: 95.40
+/- 5.20 ng/ml vs. 111.80 +/- 5.010 ng/ml, P < 0.0001; 50 mg/kg: 90.78 +/- 6.00
ng/ml vs. 111.80 +/- 5.10 ng/ml, chi2 = 17.112, P < 0.0001, respectively), ALT
(25 mg/kg: 35.78 +/- 5.01 ng/ml vs. 45.14 +/- 4.10 ng/ml, chi2 = 15.320, P <
0.0001; 50 mg/kg: 33.78 +/- 2.60 ng/ml vs. 45.14 +/- 4.10 ng/ml, chi2 = 14.023, P
< 0.0001, respectively), ALP (25 mg/kg: 2.35 +/- 0.30 ng/ml vs. 3.28 +/- 0.20
ng/ml, chi2 = 4.101, P < 0.0001; 50 mg/kg: 2.34 +/- 0.10 ng/ml vs. 3.28 +/- 0.20
ng/ml, chi2 = 2.033, P < 0.0001, respectively), and NO levels (25 mg/kg: 25.92%
+/- 2.30% vs. 38% +/- 2.09%, chi2 = 17.103, P < 0.0001; 50 mg/kg: 24.74% +/-
4.10% vs. 38% +/- 2.09%, chi2 = 25.050, P = 0.001, respectively) compared to
morphine group. Conclusion: It seems that genistein administration might improve
liver damages induced by morphine in mice.
PMID- 29941715
TI - Comparison of Placebo Effect between Asian and Caucasian Type 2 Diabetic
Patients: A Meta-Analysis.
AB - Background: Placebo was defined as any therapy that is used for its nonspecific
psychological and physiologic effect but has no specific pharmacologic impact on
the condition being treated. Besides medication therapies, studies have found
that the optimal dietary approach as well as physical activity and education are
useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim
of this study was to evaluate the placebo effects of antidiabetic therapies in
Asian and Caucasian T2DM patients and make a comparison between the two
ethnicities. Methods: A search using the MEDLINE database, EMBASE, and Cochrane
Database was performed, from when recording began until December 2016. The main
concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors
(AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4
inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon
like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo
controlled; and randomized controlled trials. Using the Cochrane instrument, we
evaluated the adequacy of randomization, allocation concealment procedures, and
blinding. Results: This study included 63 studies with a total of 7096 Asian
patients involved and 262 studies with a total of 27,477 Caucasian patients
involved. In Caucasian population, the use of placebo led to significant
reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU
monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P <
0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo
resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i
treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The
placebo also significantly reduced body weight. In Caucasian population, placebo
use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P
= 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led
to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The
changes of HbA1c and weight due to the placebo effect in other treatments were
not significant in both Asian and Caucasian population. Comparisons of the
placebo effect on HbA1c change and weight change in each treatment group
indicated that no significant difference was found between Asian and Caucasian
population. Conclusions: The overall differences of the placebo effect on HbA1c
changes as well as on body weight changes were not significant between Asian and
Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes
was not associated with baseline age, gender, baseline body mass index, baseline
HbA1c, duration of diabetes, or study duration.
PMID- 29941716
TI - Expert Consensus on Clinical Diagnostic Criteria for Fatal Familial Insomnia.
PMID- 29941718
TI - Extracorporeal Membrane Oxygenation-Assisted Percutaneous Coronary Intervention
in Extremely High-Risk Patients.
PMID- 29941717
TI - Research Progress in the Pathogenesis of Alzheimer's Disease.
AB - Objective: Alzheimer's disease (AD) is a kind of chronic degenerative disease of
the central nervous system, characteristics of cognitive dysfunction, and
behavioral disability. The pathological changes include the formation of senile
plaques-containing beta-amyloid (Abeta), neurofibrillary tangles (NFTs), loss of
neurons, and synapses. So far, the pathogenesis of AD is still unclear. This
study was aimed to review the major pathogenesis of AD-related to the published
AD studies in recent 20 years. Data Sources: The author retrieved information
from the PubMed database up to January 2018, using various search terms and their
combinations, including AD, Abeta, NFTs, pathogenesis, and genetic mutation.
Study Selection: The author included data from peer-reviewed journals printed in
English and Chinese on pathophysiological factors in AD. He organized these
informations to explain the possible pathogenesis in AD. Results: There are many
amounts of data supporting the view that AD pathogenesis so far there mainly are
Abeta toxicity, tau protein, gene mutation, synaptic damages, intermediate
neurons and network abnormalities, changes in mitochondrial function, chemokines,
etc., Its nosogenesis may be involved in multiple theories and involved in
multiple molecular signaling pathways, including Abeta, tau protein, and synaptic
anomaly; mutual relationship between the mechanisms urge jointly neuronal
degeneration. Conclusions: This review highlights the research advances in the
pathogenesis of AD. Future research has needed to fully disclose the association
between multiple pathogenesis at the same time to interdict multiple signaling
pathways, etc.
PMID- 29941719
TI - A Rare Case of Gorham-Stout Syndrome of Femur Treated with Cement Augmentation.
PMID- 29941720
TI - Mass Image in Stomach: A Case of Splenic Artery Aneurysm.
PMID- 29941722
TI - EUS-guided fine-needle tissue acquisition for solid pancreatic lesions: Finally
moving from fine-needle aspiration to fine-needle biopsy?
PMID- 29941725
TI - Pediatric eye screening - Why, when, and how.
PMID- 29941724
TI - Laparoscopic ultrasonography: The wave of the future in renal cell carcinoma?
AB - Laparoscopic or robotic surgery is the main method of treating renal cell
carcinoma (RCC). Laparoscopic surgery can accurately target lesions and shorten
patient recovery time. Renal endogenous tumors or inferior vena cava tumor
thrombi are very difficult to remove using the laparoscopic approach. The
emergence of laparoscopic ultrasonography (LUS) has solved this problem. LUS can
assist in the detection of tumor boundaries and the extent of tumor thrombi. The
lack of tactile feedback may hinder the development of laparoscopic surgery for
the treatment of renal cancer. LUS has become an important tool that has improved
the rates of successful surgery. LUS is applied in not only early and locally
advanced RCC treatment but also in monitoring ablation therapy, testing renal
blood perfusion, and exposing renal pedicles. Sonographic techniques used for LUS
include initial B-mode, Doppler, and contrast-enhanced ultrasound (CEUS).
Contrast agents applied for CEUS do not induce nephrotoxicity and can display
renal perfusion more accurately than the regular color Doppler ultrasound.
According to current literature, LUS is a promising technique for the treatment
of RCC, especially for endogenous RCC or RCC with thrombosis, and for monitoring
the effectiveness of radiofrequency ablation, although further well-designed
studies are warranted.
PMID- 29941726
TI - Paradigm shift - For effective management of diabetic retinopathy and glaucoma.
PMID- 29941727
TI - Typical optic neuritis?
PMID- 29941729
TI - Novel techniques in scleral buckling.
AB - Scleral buckling is a surgical technique that is employed successfully to treat
rhegmatogenous retinal detachments (RRD) for more than 60 years. With the
introduction of pars plana vitrectomy (PPV), there is a growing trend towards the
use of PPV for treatment of retinal detachment. There is a reluctance to perform
scleral buckling (SB) in RRD due to the perceived steep learning curve, declining
mastery over indirect ophthalmoscopy, and poor ergonomics associated with SB. In
this article, we discuss the surgical challenges and tips to overcome these in
four headings: localization of the break, retinopexy, SB, and subretinal fluid
(SRF) drainage. Localization of the break can be performed by the use of forceps
or illuminated scleral depressor. It can be facilitated by prior drainage of SRF
in cases with bullous RRD. Chandelier with wide-angle viewing system can be used
for easier localization of break and cryopexy. Sutureless buckling and
suprachoroidal buckling are easier and faster alternatives to the conventional
technique. Reshaping the silicone segment helps in accommodating the wider
circumferential band. Modified needle drainage, laser choroidotomy, and infusion
assisted drainage can make SRF drainage easier and safer. The above techniques
and other practical tips have been explained in detail with the illustrations to
make the process of learning the art of SB easier.
PMID- 29941723
TI - A quarter century of EUS-FNA: Progress, milestones, and future directions.
AB - Tissue acquisition using EUS has considerably evolved since the first EUS-FNA was
reported 25 years ago. Its introduction was an important breakthrough in the
endoscopic field. EUS-FNA has now become a part of the diagnostic and staging
algorithm for the evaluation of benign and malignant diseases of the
gastrointestinal tract and of the organs in its proximity, including lung
diseases. This review aims to present the history of EUS-FNA development and to
provide a perspective on the recent developments in procedural techniques and
needle technologies that have significantly extended the role of EUS and its
clinical applications. There is a bright future ahead for EUS-FNA in the years to
come as extensive research is conducted in this field and various technologies
are continuously implemented into clinical practice.
PMID- 29941728
TI - Polypoidal choroidal vasculopathy: Pearls in diagnosis and management.
AB - Polypoidal choroidal vasculopathy (PCV) is increasingly recognized as an
important cause of exudative maculopathy in Asians as against Wet age-related
macular degeneration in Caucasians. A panel of retinal experts methodically
evaluated pertinent updated literature on PCV with thorough PubMed/MEDLINE
search. Based on this, the panel agreed upon and proposed the current consensus
recommendations in the diagnosis (clinical and imaging), management and follow-up
schedule of PCV. Diagnosis of PCV should be based on the gold standard
indocyanine green angiography which demonstrates early nodular hyperfluorescence
signifying the polyp with additional features such as abnormal vascular network
(AVN). Optical coherence tomography is an excellent adjuvant for diagnosing PCV,
monitoring disease activity, and decision-making regarding the treatment. Current
treatment modalities for PCV include photodynamic therapy, anti-vascular
endothelial growth factor agents, and thermal laser. Choice of specific treatment
modality and prognosis depends on multiple factors such as the location and size
of PCV lesion, presence or absence of polyp with residual AVN, amount of
submacular hemorrhage, presence or absence of leakage on fundus fluorescein
angiography, visual acuity, and so on. Current recommendations would be
invaluable for the treating physician in diagnosing PCV and in formulating the
best possible individualized treatment strategy for optimal outcomes in PCV
management.
PMID- 29941730
TI - Community care for diabetic retinopathy and glaucoma in India: A panel
discussion.
AB - Diabetic retinopathy (DR) and glaucoma are emerging causes of blindness and
visual impairment in India and the world. Both diseases do not have any early
warning symptoms, and once the symptoms appear, the diseases are reasonably
advanced. Because of the long-standing nature of the diseases, one cannot adopt
the cataract detection and treatment model so successfully developed in India. It
requires an altogether different approach for screening and related
infrastructure including human capital development. The solutions developed to
reduce the burden of DR/glaucoma should be customized to urban, semi-urban, and
rural areas. Greater advocacy, improving the health-seeking behavior, development
of infrastructure and skilled personnel appropriate for the points of care, and
an emphasis in comprehensive eye care are some of the solutions.
PMID- 29941731
TI - Commentary on "Community care for diabetic retinopathy and glaucoma in India: A
panel discussion".
PMID- 29941732
TI - Comparison of the efficacy of Lea Symbol chart and Sheridan Gardiner chart for
preschool vision screening.
AB - Purpose: To compare the efficacy of Lea symbols (LS) chart and Sheridan Gardiner
(SG) chart for vision screening among preschool children, in a semi-urban
district of South India. Methods: Vision screening was conducted among 260
preschool children aged 3-5 years in cluster sampled kindergartens using LS chart
and SG chart. Pass/fail scores and time taken for visual acuity (VA) estimation
were compared. VA scores and time taken were compared using unpaired t-test.
Sensitivity, specificity, and positive and negative predictive values were
compared between the charts. Results: There was a significant difference between
LS and SG charts in the VA score in both the eyes (P = 0.04). LS showed 76.09%
pass score and 23.90% fail score, whereas SG showed 87.65% pass score and 12.35%
fail score with a cutoff value of > 0.3 log MAR. Time for screening using LS was
higher, when compared to SG, both for the right eyes (P < 0.001) and the left
eyes (P < 0.001). The sensitivity of the LS was 94.74% (95% confidence interval
[CI]: 70.13%-81.06%) and that of SG was 52.63% (95% CI: 45.29%-59.8%). The
specificity of LS was 66.67% (95% CI: 90.26%-97.30%) and SG was 83.33% (95% CI:
70.12%-91.30%). Conclusion: LS chart showed better sensitivity and negative
predictive value when compared to SG chart. However, SG chart showed better
specificity and positive predictive value, and screening was less time-consuming.
Considering the high sensitivity and negative predictive value, LS is the
preferred tool, when compared to SG chart in preschool vision screening in our
population.
PMID- 29941733
TI - Tribal Odisha Eye Disease Study # 4: Accuracy and utility of photorefraction for
refractive error correction in tribal Odisha (India) school screening.
AB - Purpose: To compare the photorefraction system (Welch Allyn SpotTM) performance
with subjective refraction in school sight program in one Odisha (India) tribal
district. Methods: In a cross-sectional study school students, aged 5-15 years,
referred after the preliminary screening by trained school teachers received
photoscreening and subjective correction. The photoscreener was compared to
subjective refraction in the range of +2D to -7.5D. Statistical analysis included
Friedman nonparametric test, Wilcoxon signed-rank test, linear regression, and
Bland-Altman plotting. Results: The photoscreener was used in 5990 children. This
analysis included 443 children (187 males, 256 females, and the mean age was
12.43 +/- 2.5 years) who received both photorefraction and subjective correction,
and vision improved to 6/6 in either eye. The median spherical equivalent (SE)
with spot photorefraction was 0.00 D (minimum -5.0D; maximum +1.6 D), and with
subjective correction was 0.00D (minimum -6.00 D; maximum +1.5 D). The difference
in the SE between the two methods was statistically significant (P < 0.001) using
Friedman nonparametric test; it was not significant for J 45 and J 180 (P = 0.39
and P = 0.17, respectively). There was a good correlation in linear regression
analysis (R2 = 0.84) and Bland-Altman showed a good agreement between
photorefraction and subjective correction in the tested range. Conclusion:
Photorefraction may be recommended for autorefraction in school screening with
reasonable accuracy if verified with a satisfactory subjective correction. The
added advantages include its speed, need of less expensive eye care personnel,
ability to refract both eyes together, and examination possibility in the native
surrounding.
PMID- 29941734
TI - Commentary on: "Tribal Odisha Eye Disease Study # 4: Accuracy and utility of
photorefraction for refractive error correction in tribal Odisha (India) school
screening".
PMID- 29941735
TI - Assessing the inclusion of primary school children in vision screening for
refractive error program of India.
AB - Purpose: In India, teachers screen middle school children using the 6/9 Snellen's
optotype. Recently, the National Program for Control of Blindness included
primary school students also. The present cross-sectional study was planned to
assess the inclusion of primary school students. Compliance to spectacles was
ascertained after 6 months follow-up. Methods: Randomly selected 23 Government
primary schools. A total of 30 teachers were nominated and given hands-on
training in vision screening and recording formats. Teachers conducted vision
screening of primary school students of their respective schools using the 6/12
Snellen's chart and referred students with subnormal vision to optometrist.
Optometrist also validated the screening done by teachers. Optometrist screened
the vision of 5% randomly selected children screened by teachers as having normal
vision. Descriptive statistics used STATA version 13.0. Results: A total of 6056
students screened by the teachers. Sensitivity and specificity of teacher
screening were 92.3% (confidence interval [CI] 88.6-95.0) and 72.6% (CI 68.2
76.6)), respectively. About 277 students underwent refraction and 186 prescribed
spectacles. The prevalence of myopia, hypermetropia, and astigmatism is 2.5% (2.1
2.9), 0.6% (0.4-0.8), and 1.3% (1.0-1.6), respectively. Compliance to spectacles
usage is 36%. Conclusion: Burden of refractive error in primary school is very
low. Trained teachers can identify children with subnormal vision, but the false
positive rate is very high. Compliance to spectacle use among primary school
children is also less. Vision screening by teachers prioritized in secondary
schools and preschool screening should be done by more skilled eye care workers
preferably optometrist.
PMID- 29941736
TI - Community outreach: An indicator for assessment of prevalence of amblyopia.
AB - Purpose: To study the prevalence, determine the magnitude, and cause of amblyopia
among the children aged 6 months to 16 years in Kamrup district, Assam, India.
Methods: Among a total of 39,651 children between 6 months and 16 years of age,
door-to-door screening was conducted by trained workers. For children above 5
years of age who failed to read the 6/9 line, camps were conducted in the nearby
schools. Children below 5 years of age were directly referred to the tertiary eye
care institute. After visual acuity assessment at the institute, cycloplegic
refraction and complete ophthalmic examination were done to rule out other causes
of diminution of vision. Axial length measurement and corneal topography were
performed in children with high refractive errors. Results: Of the total 39,651
children screened, 469 were diagnosed to have amblyopia at the camp and 223 were
diagnosed at the institute. The prevalence of amblyopia was 1.75%. Amblyopia was
more common among the males (52.50%) as compared to females. Maximum number of
patients were found in the age group of 11-16 (63.58%). Refractive amblyopia was
found to be the most common cause of amblyopia (45.29%). In children below 5
years, deprivation amblyopia and strabismic amblyopia were more common.
Conclusion: Awareness of amblyopia among the parents is essential for early
detection and treatment of the disease, which will, in turn, reduce the burden of
childhood visual impairment.
PMID- 29941737
TI - Spectacle compliance among adolescents in Southern India: Perspectives of service
providers.
AB - Purpose: Compliance to spectacle wear is vital to elimination of avoidable
blindness among schoolchildren. This study aims to understand the barriers to
compliance and strategies to overcome the barriers from the perspectives of the
service providers of the school vision-screening model. Methods: A snapshot
qualitative study using focus group discussions (FGDs) was conducted among the
service providers including eye care professionals (ECPs) and social workers that
are part of the school screening program. Sessions were audio recorded and
transcribed. Themes were formed following inductive coding using a conceptual
framework. Results: Out of the three FGDs, two were with ECPs and one with social
workers. Four subthemes identified under the barriers were poor awareness,
spectacle-related, psychosocial, and financial barriers. Unique barriers
according to the service providers included nonuse of spectacles by asymptomatic
children, children with unilateral refractive errors and those with emmetropic
parents. Service providers also brought out parent's feelings of guilt, doubts
about their children's impaired vision, the negative self-image among children,
and difficulties in obtaining funding to support the costs of screening.
Solutions that emerged included the personal visit of professionals for spectacle
distribution and counseling parents, demonstration of improvement in vision for
activities that were difficult for the children without spectacles and rewarding,
and role modeling of compliant children. Conclusion: This study had identified
unique barriers and solutions from the perspectives of the service providers. The
suggested strategies would aid in an effective schoolchildren vision screening
practice to enhance compliance to spectacle wear.
PMID- 29941738
TI - Prevalence and causes of visual impairment among adults aged 15-49 years in a
rural area of north India - A population-based study.
AB - Purpose: Very few studies have been conducted in India and other parts of the
world on visual impairment among individuals aged 15-49 years. This study was
conducted to determine the prevalence, causes, and associated factors of visual
impairment among adults aged 15-49 years in a rural population of Jhajjar
district, Haryana, north India. Methods: A population-based cross-sectional study
was conducted in two blocks of Jhajjar district. A total of 34 villages were
selected using probability proportionate to size sampling method. Adults aged 15
49 years were selected using compact segment cluster sampling approach. As part
of the house-to-house survey, presenting visual acuity using screening chart
corresponding to five "E" 6/12 optotypes was measured along with collection of
other demographic details. The optometrists performed detailed eye assessment
including repeat measurement of visual acuity using retro-illuminated
conventional logMAR tumbling "E" charts, torch light examination, and non
cycloplegic refraction at a clinic site within the village to ascertain visual
impairment and its cause. Results: Of 5,470 enumerated adults, 5,117 (94%)
completed all study procedures. The age- and sex-adjusted prevalence of visual
impairment was found to be 1.85% [95% confidence interval (CI): 1.48, 2.23] and
blindness was 0.09% (95% CI: 0.01, 0.18). The age- and sex-adjusted prevalence of
unilateral visual impairment was 1.11% (95% CI: 0.81, 1.41). Uncorrected
refractive errors (84%) contributed maximum to visual impairment in this age
group. The visual impairment in study participants was found to be associated
with age and educational status. Conclusion: At the community level, uncorrected
refractive errors contribute largely to visual impairment in the age group of 15
49 years.
PMID- 29941739
TI - Incorporating primary eye care into primary health care: Piloting a perceived
visual disability questionnaire based model in rural southern India - An
observational study.
AB - Purpose: Over 20% of the world's visually impaired and blind populations live in
India. Integration of primary eye care (PEC) into existing primary health care by
trained personnel could address access-related barriers. We piloted an
unreported, modified WHO disability questionnaire-based model for community
health workers (CHWs) to screen and refer persons with perceived visual
impairment instead of the traditional visual acuity model. The objective of the
study was (1) to determine the prevalence of perceived visual impairment, rate of
follow-up postreferral, distribution of ocular morbidity, visual impairment, and
proportion of appropriate referrals and (2) to compare results of this
intervention with those of existing services. Methods: CHWs were trained in
administering a questionnaire for identification and referral of persons with
perceived visual impairment in 7 rural villages and 22 tribal hamlets from the
institutional database. In this cross-sectional study, patients screened and
referred to PEC services from September 2014 to March 2015 underwent
comprehensive ocular examination by an optometrist and ophthalmologist. Data
collected from their records were analyzed retrospectively. Results: Of 18,534
individuals screened, 3082 (16.64%, 95% confidence interval: 16.06-17.14)
complained of perceived visual impairment and were referred; 463 (15%) of these
followed up for examination. Correct referrals were noted in 452 (97.6%) cases.
Cataract (52.3%) and refractive error (15.8%) were the most common morbidities.
There was a 39.6% increase in uptake of eye care services from baseline.
Conclusion: The questionnaire-based screening tool administered by CHWs can lead
to appropriate identification and referral of persons with ocular morbidity
impacting uptake of eye care services.
PMID- 29941740
TI - Facilitating factors in overcoming barriers to cataract surgical services among
the bilaterally cataract blind in Southern India: A cross-sectional study.
AB - Purpose: To effectively address cataract blindness, increasing sight-restoring
surgeries among the bilaterally blind are essential. To improve uptake of
surgical services among this group, evidence regarding the problems of access is
vital. Barriers in accessing eye care services have previously been reported but
not specific to bilaterally cataract blind patients. Further, there is a gap in
knowledge regarding factors facilitating access to eye care. Our aims were to (1)
report proportion of bilaterally cataract blind patients undergoing surgery and
sight restoration rate (SRR) and (2) analyze barriers and factors enabling access
to eye care services among bilaterally cataract blind patients. Methods:
Retrospective analysis of interview and clinical data of bilaterally cataract
blind patients undergoing surgery through outreach services at the base hospital,
from June 2015 to May 2016, was performed. Demographic data, vision,
postoperative visual outcomes, barriers, and facilitating factors in accessing
cataract surgical services were obtained. Results: Bilateral cataract blindness
was present in 196/3178 (6.2%, 95% confidence interval 5.4-7.06) patients. SRR
was 6.5%. Fear of surgery (24.2%) and lack of family support/escort (22.9%) were
the most common barriers. Neighbors and acquaintances (28.6%), general health
workers (20.2%), and persons who had undergone cataract surgery (19.6%) were the
most common facilitating factors. Conclusion: Proportion of bilaterally cataract
blind people undergoing surgery and consequently SRR were low. The most common
barriers were at the individual level while facilitating factors at the community
level were instrumental in promoting uptake of services. Interventions involving
community-based support for the blind may be useful in overcoming barriers to eye
care.
PMID- 29941742
TI - Ophthalmic problems in remote areas of India.
PMID- 29941741
TI - Factors limiting the Northeast Indian elderly population from seeking cataract
surgical treatment: Evidence from Kolasib district, Mizoram, India.
AB - Purpose: Reliable data on the barriers to the uptake of cataract surgical
services in the Northeast Indian states are scanty. The purpose of this study was
to assess the barriers to uptake of cataract surgical services among elderly
patients and suggest appropriate strategies to reduce these. Methods: A cross
sectional study was conducted among patients who failed to avail cataract
surgical services, 6-12 months' postinitial diagnosis at a community eye health
camp. Validated questionnaire was used to collect information through face-to
face interviews at the residence of the participants. Descriptive statistics and
Chi-square tests were conducted to assess the association between the barriers
quoted and sociodemographic variables. Results: A total of 140 (89.2%)
individuals participated in the study, of whom 56 (40%) were aged between 71 and
80 years. The median age for men and women was 73.5 and 72.5 years, respectively.
About 57% of participants were female patients. A total of 66 (47.1%)
participants had borderline visual acuity followed by those with poor vision
(41.4%, n = 58). "Bad roads/difficult terrain" (P = 0.009), "witnessed bad
surgical outcomes in others" and "did not feel important" (P < 0.024), "poor
overall health status" (P < 0.001), "lack of information" (P = 0.025) and "no
escort" (P = 0.025) were significant barriers reported by this population.
Conclusion: Most of the barriers reported in this study seem to be endogenous in
nature and appear to be within the purview of the local eye care service provider
to remedy. Counseling and targeted awareness and information, education, and
communication strategies could nullify many of the barriers reported in this
study.
PMID- 29941743
TI - Association of obesity and age-related macular degeneration in Indian population.
AB - Purpose: The aim of this study was to establish the prevalence and association of
age-related macular degeneration (AMD) and obesity which was not studied
extensively in Indian population over 60 years of age. Methods: This was a cross
sectional, population-based study. A total of 4791 patients with gradable fundus
photography were included. All patients underwent detailed ophthalmic examination
and AMD was graded with retinal photographs. Grading of AMD was done according to
the International ARM Epidemiological Study Group and staged based on grading in
worse eye. The association of AMD severity and obesity (based on body mass index,
waist-hip ratio, waist circumference, isolated abdominal obesity, isolated
generalized obesity, and combined obesity) was assessed. The main outcome
variable was an association between the presence and severity of AMD with
different grades of obesity. Results: No direct significant association was noted
between the presence and severity of AMD and any obesity indices. Subgroup
analyses based on lifestyle patterns and common systemic pathologies in AMD
population were done. Late AMD was significantly associated with tobacco
consumption in population with combined obesity (P = 0.033 and odds ratio =
2.998). Conclusion: No direct association was noted between the presence or
severity of AMD and obesity in South Indian population. However, indirect
associations between the severity of AMD and combined obesity were found.
PMID- 29941744
TI - Management of late-onset flocculent after-cataract with capsular bag lavage and
posterior continuous curvilinear capsulorhexis.
AB - We describe our technique for the management of late-onset liquefied after
cataract (LAC) to ensure long-term visual axis clarity. The densely adherent
anterior capsular rim over the intraocular lens (IOL) optic was released with the
help of microvitreoretinal blade, and multiple relaxing radial incisions were
made on the capsular rim to facilitate easy access to the capsular bag. A
thorough capsular bag lavage was performed with the help of bimanual irrigation
aspiration. Posterior continuous curvilinear capsulorhexis (PCCC) was performed
after complete aspiration of fluid after-cataract to prevent recurrence. This
technique was successfully performed in 14 cases. Postoperatively, IOL was stable
and an uncorrected distance visual acuity of >20/32 was achieved in all cases. No
recurrence was observed in any case over a follow-up of 1 year. Our technique of
capsular bag lavage with PCCC is safe and effective for the management of LAC
with optimal visual and anatomical outcomes.
PMID- 29941745
TI - Sandwich technique using a combination of perfluoropropane and silicone oil for
inferior retinal detachment.
AB - We report a novel surgical sandwich technique using a combination of intraocular
perfluoropropane (C3F8) and silicone oil for inferior retinal detachment (RD).
After conventional pars plana vitrectomy and posterior vitreous detachment
induction, fluid-gas exchange using 14% C3F8was done. This was followed by
silicone oil injection using automated infusion pump to 50% fill of the vitreous
cavity under direct visualization to achieve formation of two bubbles - gas
bubble superiorly and silicone oil inferiorly. The patient was subsequently asked
to maintain upright position. The two immiscible bubbles of C3F8and silicone oil
provide tamponade to superior and inferior retina, respectively. With time, gas
bubble reduces in size with a gradual superior shift of silicone oil. This novel
sandwich technique achieves complete attachment of retina and reduces the risk of
retinal redetachment in inferior RDs by adequately tamponading the inferior
retina.
PMID- 29941746
TI - Conjunctival vegetative foreign body in a child mimicking shield ulcer.
PMID- 29941747
TI - Clinical presentation following photorefractive intrastromal cross-linking for
myopic correction.
PMID- 29941748
TI - Multimodal imaging of choroidal tubercles.
PMID- 29941749
TI - Ultra-widefield imaging in Coats'-type retinitis pigmentosa.
PMID- 29941750
TI - Foveolar simple retinal pigment epithelial hamartoma.
PMID- 29941752
TI - Gear up for work!
PMID- 29941751
TI - Intralenticular foreign body.
PMID- 29941753
TI - Traumatic optic nerve head avulsion: Multimodal imaging.
PMID- 29941754
TI - Vernal keratoconjunctivitis in human immunodeficiency virus - The possible role
of T-helper 1-T-helper 2 shift.
AB - Human immunodeficiency virus infection (HIV) is associated with a reduced T
helper (Th) 1 response, and vernal keratoconjunctivitis (VKC) occurs secondary to
a heightened Th2 response. VKC has been reported to occur in patients with HIV.
In all probability, a Th1-Th2 shift occurs in the immune response in progressive
HIV patients with a decreasing CD4 count. This shift could be the probable cause
for the initiation and gradual worsening of the VKC in our patient that
corresponded to the dropping CD4 counts. VKC resolved only after a change in
antiretroviral therapy for HIV that caused a demonstrable increase in the CD4
counts possibly by reversing the shift.
PMID- 29941755
TI - A case of human leukocyte antigen B-27-associated ocular hypotony successfully
treated with golimumab.
AB - A 42-year-old male presented to us after an episode of acute anterior human
leukocyte antigen (HLA)-B27-associated uveitis, and intraocular pressure (IOP) in
the right eye was 4 mmHg. Ultrasound biomicroscopy revealed ciliary body edema
with supraciliary effusion. He was on a frequent topical corticosteroid, and oral
steroid in addition to receiving a periocular injection depot corticosteroid 20
days back. He was started on treatment with subcutaneous golimumab (GLM). After a
month, his IOP in the right eye was 14 mm of Hg with UBM showing resolution of
ciliary body edema. GLM can be useful in the management of steroid-resistant
cases of HLA B-27-associated ocular hypotony.
PMID- 29941756
TI - Misplaced capsule tension ring in anterior chamber: A unique way of explantation.
AB - We report a patient who presented with endocapsular capsule tension ring (CTR) in
iridocorneal angle leading to secondary angle closure glaucoma (ACG) and
subsequent removal of the CTR from trabeculectomy ostium. Secondary ACG was
diagnosed 2 years and 6 months after cataract surgery in which a CTR was used for
zonular instability. CTR removal with trabeculectomy was performed, after which
there was the resolution of symptoms. To the best of our knowledge, this is the
first case report in which CTR was removed from trabeculectomy ostium. We
describe a surgical technique to explant CTR and combining with trabeculectomy.
PMID- 29941757
TI - Commentary on "Misplaced capsule tension ring in anterior chamber: A unique way
of explantation".
PMID- 29941758
TI - Management of Candida glabrata infectious crystalline keratopathy with
endophthalmitis following penetrating keratoplasty.
AB - A 33-year-old male underwent an optical keratoplasty elsewhere in the right eye
following which he developed endophthalmitis and subsequently underwent a pars
plana vitrectomy and lensectomy. At presentation, he had a deep stromal
crystalline infiltration along the graft-host junction. A large therapeutic
keratoplasty was performed, and the excised corneal button was evaluated.
Histopathology revealed gram-positive round-to-oval budding structures and
microbiology identified the organism as Candida glabrata. He was treated with
antifungals in the postoperative period. At 4 months after therapeutic
keratoplasty, the patient developed recurrent endophthalmitis, following stoppage
of antifungals. The treatment was reinstituted for another year, and the patient
did well with a clear graft at 18-month-follow-up period after the recurrence
episode. Management of infectious crystalline keratopathy with endophthalmitis is
a challenging situation and requires long-term treatment.
PMID- 29941759
TI - Endogenous Cryptococcus neoformans endophthalmitis with subretinal abscess in a
HIV-infected man.
AB - To report a rare case of Cryptococcus neoformans endogenous endophthalmitis with
subretinal abscess in a 36-year-old HIV-positive man, referred with progressive
blurred vision in his right eye for the last 6 months. Vitreous biopsy followed
by intravitreal ganciclovir did not result in significant improvement.
Microbiology revealed the presence of C. neoformans, and intravitreal
amphotericin B was then administered. The patient was treated aggressively with
systemic and intravitreal antifungals but had a poor visual and anatomical
outcome. A high degree of clinical suspicion combined with microbiological
evaluation helped to arrive at an appropriate diagnosis.
PMID- 29941760
TI - Culture-positive unilateral panophthalmitis in a serology-positive case of dengue
hemorrhagic fever.
AB - Dengue fever, a mosquito-borne disease commonly found in the tropics, is one of
the most prevalent forms of Flavivirus infection in humans. Symptomatically, it
is characterized by fever, arthralgia, headache, and rash. Ophthalmic
manifestations can involve both the anterior and posterior segment.
Panophthalmitis is rare in dengue hemorrhagic fever, and there is no report of
culture-positive panophthalmitis in this setting. Here, we report a case of a
serology-positive 33-year-old male patient of dengue hemorrhagic fever who
developed sudden onset pain, redness, and proptosis in the right eye. The patient
subsequently developed panophthalmitis in his right eye, and Bacillus cereus was
isolated from eviscerated sample. This case provides unique insights into
pathogenesis of panophthalmitis in dengue and highlights the management options.
PMID- 29941761
TI - Central retinal arterial occlusion in a patient with pyoderma gangrenosum.
AB - A 74-year-old male presented to us with a history of vision loss for 36 hours in
the right eye (RE). The RE had a visual acuity of hand movements. The fundus
revealed a pale retina, cattle tracking in the retinal vessels, and a cherry-red
spot at the macula. The patient was a known case of pyoderma gangrenosum (PG) and
had received intravenous methylprednisolone and cyclophosphamide at the onset of
visual symptoms. An emergency anterior chamber paracentesis was performed
following unsuccessful attempts of ocular massage. The patient improved to 6/9 in
the RE 4 months after paracentesis. The patient had an aggressive course of PG,
for which he needed a combination of oral steroid, immunomodulator therapy and
biologicals. An association between central retinal arterial occlusion and PG has
not been reported before, according to the best of authors' knowledge.
PMID- 29941762
TI - Validating the pachychoroid disease spectrum using multimodal imaging.
AB - Pachychoroid disease spectrum has garnered considerable interest and has been
discussed in detail in recent literature. It refers to a group of retinal and
choroidal disorders, namely pigment epitheliopathy, central serous
chorioretinopathy, neovasculopathy, and polypoid choroidal vasculopathy, all
arising from a thickened choroid and hyperpermeable large choroidal vessels. We
describe a case which had simultaneous presentation of multiple disorders on the
pachychoroid spectrum. Multimodal findings in this patient have been described in
this report. The presence of pachychoroid should prompt thorough imaging since
coexistence of multiple disorders can potentially change the management and
follow-up schedule of these patients.
PMID- 29941763
TI - Multimodal imaging of Bietti's crystalline dystrophy.
AB - Bietti's crystalline dystrophy (BCD) is a rare autosomal recessive retinal
dystrophy characterized by deposition of crystals in the retina. The purpose of
this article is to describe retinal abnormalities in BCD using multimodal
imaging. An 18-year-old girl presented with decrease of vision and nyctalopia.
She was assessed with color fundus picture, red-free photographs, short-wave
autofluorescence, spectral-domain optical coherence tomography (OCT) and en face
OCT and was diagnosed to have BCD based on typical presentation. Retinal crystals
were better visualized on en face OCT as compared to conventional B scan OCT.
PMID- 29941764
TI - Intercalary membrane as the inner wall overlying optic and chorio-retinal
colobomas. Deep penetration Swept Source-OCT study.
AB - Five eyes of four patients were studied to analyze the structure of the inner
wall of optic and chorioretinal colobomas using swept-source optical coherence
tomography (SS-OCT). The colobomatous cavities and their relationship with
adjacent structures were examined. SS-OCT permitted the study of the colobomatous
cavities in all cases. In four of those cases, a Y-shaped intercalary membrane
(ICM) was identified, with an origin in the retinal nerve fiber layer (RNFL),
which covered the coloboma and in one case the coloboma was in contact with the
vitreous cavity. Vitreous adhesion to the internal wall of the coloboma was found
in three cases. No clinical or tomographic maculopathy was observed in any
patient. High-resolution deep penetration SS-OCT allows in vivo study of optic
and chorioretinal colobomas, identifying the RNFL as the main component of the
ICM overlying the colobomatous cavities.
PMID- 29941765
TI - Frosted branch angiitis with penetrating ocular trauma and retained intraocular
foreign body.
AB - A 54-year-old male sustained ocular trauma with a projectile. Examination of the
right eye revealed an intraocular foreign body (IOFB) adjacent to the optic nerve
head, vitritis, vitreous hemorrhage, and translucent perivascular sheathing of
the retinal vessels in all quadrants suggesting frosted branch angiitis (FBA).
The patient underwent vitrectomy with removal of the IOFB and silicone oil
tamponade under steroid cover. With continued use of systemic and topical
steroids after surgery, complete resolution of FBA and improvement in vision were
noted in a week. Prompt resolution of FBA after IOFB removal points toward a
strong association between the presence of IOFB and FBA.
PMID- 29941766
TI - Pars plana vitrectomy and re-directing a dexamethasone implant into vitreous
cavity following misdirected entry into the crystalline lens.
AB - A known diabetic patient presented with diabetic macular edema (DME) and
nonproliferative diabetic retinopathy in both eyes with a vision of 6/18, N12in
the right eye and 4/60, N36in the left eye (LE). The patient had undergone
injection of dexamethasone implant in the LE which got misdirected into the
crystalline lens. The patient was taken up for phacoemulsification with
intraocular lens implantation along with vitrectomy and posterior vitreous
detachment induction, and redirection of the dexamethasone implant into the
vitreous cavity. The DME resolved over the next 3 months.
PMID- 29941767
TI - Weber syndrome secondary to brain stem tuberculoma.
AB - This case report describes a rare presentation of presumed brain stem tuberculoma
in a 28-year-old male who presented with acute onset of third cranial nerve palsy
with contralateral hemiparesis (Weber syndrome) and upgaze palsy. Isolated
midbrain tuberculoma is rare, presenting with varied clinical manifestations and
radiological findings posing as a diagnostic dilemma. Weber syndrome is commonly
caused by midbrain infarct secondary to occlusion of branches of the posterior
cerebral artery and rarely from a tuberculoma. The patient is a case of
disseminated tuberculosis with granuloma in midbrain causing pressure effect,
thereby presenting with features consistent with Weber syndrome and upgaze palsy.
The patient had good recovery with antitubercular treatment and systemic
steroids.
PMID- 29941768
TI - Optic nerve avulsion associated with central retinal artery occlusion following
rotational globe injury.
AB - Avulsion of the optic nerve head is a rare and severe complication of ocular
blunt trauma. Herein, we describe a case of 16-year-old boy, who presented with a
rare combination of optic nerve avulsion associated with central retinal artery
occlusion, following blunt trauma with a leather ball. This report highlights the
potential blinding complication following rotational injury.
PMID- 29941769
TI - Endocrine mucin-producing sweat gland carcinoma of the eyelid: A clinical and
histological conundrum.
AB - A 60-year-old male presented with a 6-month-old history of a left upper lid mass.
The mass was excised, and histopathological evaluation showed a well
circumscribed, multinodular, intradermal tumor consisting of round-to-oval cells
with round nuclei and mucin filled cysts. On immunohistochemical analysis, the
tumor cells stained positively for cytokeratin (CK)-7, CK-8, estrogen receptor
(ER), progesterone receptor (PR), mucicarmine, synaptophysin, gross cystic
disease fluid protein-15 (GCDFP-15), and neuron-specific enolase (NSE). A
diagnosis of endocrine mucin-producing sweat gland carcinoma (EMPSGC) of the
eyelid was made and at 6-month follow-up, no recurrence was noted. In this
communication, we discuss the pathology and treatment options of EMPSGC of the
eyelid. Although an uncommon entity, EMPSGC may be considered as a differential
when encountered with a suspicious, potentially malignant eyelid mass.
PMID- 29941770
TI - July 1 is National Doctors' Day: How to regain the lost public trust in
healthcare?
PMID- 29941771
TI - 5% cefuroxime as an alternative to 5% cefazolin in the treatment of Gram-positive
bacterial keratitis.
PMID- 29941772
TI - Commentary on "Intravitreal dexamethasone implant for management of treatment
naive retinal vein occlusion".
PMID- 29941773
TI - Comments on "Bilateral medial rectus palsy due to midbrain infarction following
concussion head injury".
PMID- 29941774
TI - BAS2 Is Required for Conidiation and Pathogenicity of Colletotrichum
gloeosporioides from Hevea brasiliensis.
AB - The hemibiotrophic fungi Colletotrichum gloeosporioides can cause anthracnose in
rubber trees. By searching the genome of the fungal pathogen, the BAS2 encoding a
biotrophy-associated secreted protein was identified. In the present study, the
knockout mutants of BAS2 were constructed and the functions of BAS2 were
investigated. The in vitro assays showed that BAS2 was not necessary for
vegetative growth but was important for normal asexual reproduction in C.
gloeosporioides. Pathogenicity assays suggested that BAS2 was involved in the
process of the pathogen penetrating into the host tissue. Subcellular
localization analysis revealed that BAS2 showed secretional characteristics in
the fungi, and BAS2 mainly function as a cytoplasmic protein after being secreted
into the host cell. Extracellular proteomics analysis revealed that BAS2 was
required for the secretion of a series of proteins, which were important for the
pathogenicity of C. gloeosporioides. These data lead to a better understanding of
the biotrophy-associated secreted protein in regulating the pathogenesis of C.
gloeosporioides.
PMID- 29941775
TI - Compressive Sensing Based Multilevel Fast Multipole Acceleration for Fast
Scattering Center Extraction and ISAR Imaging.
AB - In recent years, Compressive Sensing (CS) theory has been very popular in the
data sensing and process area as it utilizes the sparsity and measurement matrix
to reconstruct the compressible signal from limited samples successfully. In this
paper, CS is introduced into an efficient numerical method, multilevel fast
multipole acceleration (MLFMA), for the electromagnetic (EM) scattering problem
over a wide incident angle. This allows composition of a new kind of incident
wave, which obtains efficient and reliable data for scattering centers extraction
with low complexity. The resulting data from CS-based MLFMA are processed for
ISAR) imaging. Simulation results show the received data for ISAR imaging from
MLFMA with CS can outperform the data from MLFMA, which achieves a similar
quality of ISAR imaging. Additionally, the computation complexity is improved by
CS through the reduced matrix computation for fewer incident waves. It makes ISAR
imaging using real data feasible and meaningful.
PMID- 29941776
TI - Improving Cardiovascular Disease Knowledge among Rural Participants: The Results
of a Cluster Randomized Trial.
AB - Cardiovascular disease (CVD) is a major cause of death and disability, especially
among people living in the rural, southern United States. Rural African Americans
are often diagnosed with CVD earlier in life, and they bear a disproportionate
burden of CVD risk factors, morbidity, and mortality. Health equity among
historically underserved, rural populations can potentially be attained through
culturally relevant interventions that teach people skills to stay well and avoid
CVD-related risk and diagnoses. The purpose of this secondary analysis was to
determine the effect of an evidence-based intervention on cardiovascular health
knowledge and the stages of change toward the action and maintenance phases. The
pre-test-post-test data were obtained during a cluster randomized trial involving
twelve rural churches that were randomized to intervention (n = 6) and control (n
= 6) groups. Participants (n = 115) in the intervention group received a
cardiovascular health intervention, and those (n = 114) in the control group
could receive the intervention following the study’s completion. The data
were analyzed using a linear mixed model to compare group differences from pre
test to post-test. The cardiovascular health promotion intervention significantly
improved cardiovascular health knowledge and was associated with advancements in
the stages of change toward the action and maintenance phases.
PMID- 29941778
TI - Celiac Disease and Glandular Autoimmunity.
AB - Celiac disease is a small intestinal inflammatory disease with autoimmune
features that is triggered and maintained by the ingestion of the storage
proteins (gluten) of wheat, barley, and rye. Prevalence of celiac disease is
increased in patients with mono- and/or polyglandular autoimmunity and their
relatives. We have reviewed the current and pertinent literature that addresses
the close association between celiac disease and endocrine autoimmunity. The
close relationship between celiac disease and glandular autoimmunity can be
largely explained by sharing of a common genetic background. Further, between 10
and 30% of patients with celiac disease are thyroid and/or type 1 diabetes
antibody positive, while around 5-7% of patients with autoimmune thyroid disease,
type 1 diabetes, and/or polyglandular autoimmunity are IgA anti-tissue
transglutaminase antibody positive. While a gluten free diet does not reverse
glandular autoimmunity, its early institution may delay or even prevent its first
manifestation. In conclusion, this brief review highlighting the close
association between celiac disease and both monoglandular and polyglandular
autoimmunity, aims to underline the need for prospective studies to establish
whether an early diagnosis of celiac disease and a prompt gluten-free diet may
positively impact the evolution and manifestation of glandular autoimmunity.
PMID- 29941779
TI - The Association between Molar-Incisor Hypomineralization and Dental Caries with
Socioeconomic Status as an Explanatory Variable in a Group of Finnish Children.
AB - The aim of this study was to investigate if a developmental enamel defect known
as Molar-Incisor Hypomineralization (MIH) is associated with dental caries.
Socioeconomic status (SES) was examined as a confounding factor between caries
and MIH. In this cross-sectional study, 636 children, aged 8 to 13 years, from
three towns (two rural areas and one urban area) in Finland were examined for MIH
in line with the criteria of the European Academy of Paediatric Dentistry. Caries
status for permanent teeth was recorded as decayed, missing and filled teeth
(DMFT). Caries experience (DMFT > 0) in the first permanent molars (FPMs) was set
as an outcome. SES was determined using a questionnaire completed by parents. The
prevalence of MIH was 18.1%. The mean DMFT in FPMs for children with MIH was
higher than for their peers, 1.03 +/- 1.25 vs. 0.32 +/- 0.80 (p = 0.000, Mann
Whitney U test). In a multivariate analysis using the generalized linear mixed
model where locality, SES, age and MIH were taken into account as caries risk
indicators, MIH was the strongest risk indicator of caries in FPMs (Odds Ratio:
6.60, 95% Confidence Interval: 3.83-11.39, p = 0.000). According to the study
results, children with MIH have a higher risk for dental caries than children
without MIH.
PMID- 29941777
TI - Potential Micronutrients and Phytochemicals against the Pathogenesis of Chronic
Obstructive Pulmonary Disease and Lung Cancer.
AB - Lung cancer and chronic obstructive pulmonary disease have shared etiology,
including key etiological changes (e.g., DNA damage and epigenetics change) and
lung function impairment. Focusing on those shared targets may help in the
prevention of both. Certain micronutrients (vitamins and minerals) and
phytochemicals (carotenoids and phenols) have potent antioxidant or methyl
donating properties and thus have received considerable interest. We reviewed
recent papers probing into the potential of nutrients with respect to lung
function preservation and prevention of lung cancer risk, and suggest several
hypothetical intervention patterns. Intakes of vitamins (i.e., A, C, D, E, B12),
carotenoids, flavonoids, curcumins, resveratrol, magnesium, and omega-3 fatty
acids all show protective effects against lung function loss, some mainly by
improving average lung function and others through reducing decline rate. Dietary
interventions early in life may help lung function reserve over the lifespan.
Protective nutrient interventions among smokers are likely to mitigate the
effects of cigarettes on lung health. We also discuss their underlying mechanisms
and some possible causes for the inconsistent results in observational studies
and supplementation trials. The role of the lung microbiome on lung health and
its potential utility in identifying protective nutrients are discussed as well.
More prospective cohorts and well-designed clinical trials are needed to promote
the transition of individualized nutrient interventions into health policy.
PMID- 29941780
TI - The Preservation of Bone Cell Viability in a Human Femoral Head through a
Perfusion Bioreactor.
AB - Current methods for drug development and discovery involve pre-clinical analyses
that are extremely expensive and time consuming. Animal models are not the best
precedent to use, when comparing to human models as they are not synonymous with
the human response, thus, alternative methods for drug development are needed.
One of which could be the use of an ex vivo human organ where drugs could be
tested and the effects of those drugs could be observed. Finding a viable human
organ to use in these preliminary ex vivo studies is difficult due to the
availability, cost, and viability. Bone tissue and marrow contain a plethora of
both bone and stem cells, however, these cells need constant perfusion to be
viable over a longer time range. Here we maintain bone cell sustainability in an
ex vivo model, through the use of human femoral heads in a novel bioreactor. This
bioreactor was designed to directly perfuse cell culture media (DMEM) through the
vasculature of a femoral head, providing ideal nutrients and conditions required
for maintaining organ viability. We show, for the first time, that cells within a
femoral head can stay alive up to 12 h. Further development could be used to
determine the effects of drugs on a human organ system and could aid in the
understanding of the progression of bone diseases and pathologies.
PMID- 29941781
TI - Forensic Use of the Five Domains Model for Assessing Suffering in Cases of Animal
Cruelty.
AB - Conceptual frameworks for understanding animal welfare scientifically are widely
influential. An early “biological functioning” framework still
influences expert opinions prepared for Courts hearing animal cruelty cases,
despite deficiencies in it being revealed by the later emergence and wide
scientific adoption of an “affective state” framework. According to
“biological functioning” precepts, indices of negative welfare states
should predominantly be physical and/or clinical and any that refer to
animals’ supposed subjective experiences, i.e., their “affective
states”, should be excluded. However, “affective state”
precepts, which have secure affective neuroscience and aligned animal behaviour
science foundations, show that behavioural indices may be utilised to credibly
identify negative welfare outcomes in terms of negative subjective experiences,
or affects. It is noted that the now very wide scientific acceptance of the
“affective state” framework is entirely consistent with the current
extensive international recognition that animals of welfare significance are
“sentient” beings. A long list of negative affects is discussed and
each one is described as a prelude to updating the concept of
“suffering” or “distress”, often referred to in animal
welfare legislation and prosecutions for alleged ill-treatment of animals. The
Five Domains Model for assessing and grading animal welfare compromise is then
discussed, highlighting that it incorporates a coherent amalgamation of
“biological functioning” and “affective state” precepts
into its operational features. That is followed by examples of severe-to-very
severe ill-treatment of dogs. These include inescapable psychological and/or
physical abuse or mistreatment, excessively restrictive or otherwise detrimental
housing or holding conditions, and/or seriously inadequate provision of the
necessities of life, in each case drawing attention to specific affects that such
ill-treatment generates. It is concluded that experts should frame their opinions
in ways that include negative affective outcomes. Moreover, the cogency of such
analyses should be drawn to the attention of the Judiciary when they are
deliberating on suffering in animals, thereby providing a basis for them to move
from a current heavy reliance on physical and/or clinical indices of cruelty or
neglect towards including in their decisions careful evaluations of
animals’ negative affective experiences.
PMID- 29941783
TI - Improved Performance of Perovskite Light-Emitting Diodes by Quantum Confinement
Effect in Perovskite Nanocrystals.
AB - In this study, we demonstrate an easy and reliable solution-processed technique
using an extra adductive in the perovskite precursor solution. Using this method,
a dense and uniform morphology with full surface coverage and highly fluorescent
films with nanoscale crystal grains can be obtained. The high exciton binding
energy in the resulting films employing octylammonium bromide (OAB) adductives
proved that high fluorescence originated from the quantum confinement effect. The
corresponding perovskite light-emitting diodes (PeLEDs) that were based on this
technique also exhibited excellent device performance.
PMID- 29941782
TI - Optimal Adherence to a Mediterranean Diet May Not Overcome the Deleterious
Effects of Low Physical Fitness on Cardiovascular Disease Risk in Adolescents: A
Cross-Sectional Pooled Analysis.
AB - To examine the combined association of cardiorespiratory fitness (CRF), muscular
fitness (MF), and adherence to a Mediterranean diet (MeDiet) on cardiovascular
risk in adolescents, a pooled study, including cross-sectional data from two
projects [2477 adolescents (1320 girls) aged 12-18 years], was completed. A
shuttle run test was used to assess CRF. MF was assessed by the standing-long
jump and handgrip tests. Adherence to a MeDiet was assessed by the Kidmed
questionnaire. A cardiovascular risk score was computed from the following
components: Age and sex, waist circumference, triglycerides, systolic blood
pressure, high-density lipoprotein cholesterol (HDL), and glucose. Analysis of
covariance showed that participants classified as having optimal (High) adherence
to a MeDiet/HighMF/HighCRF, as well those classified as low adherence to a
MeDiet/HighMF/HighCRF, had, on average, the lowest cardiovascular risk score (F =
15.6; p < 0.001). In addition, the high adherence to a MeDiet/LowMF/LowCRF group
had the highest odds of having a high cardiovascular risk (OR = 7.1; 95% CI: 3.4
15.1; p < 0.001), followed by the low adherence to a MeDiet/LowMF/LowCRF group
(OR = 3.7; 95% CI: 2.2-6.3; p < 0.001), high adherence to a MeDiet/HighMF/LowCRF
group (OR = 3.1; 95% CI: 1.4-7.0; p = 0.006), and low adherence to a
MeDiet/LowMF/HighCRF group (OR = 2.5; 95% CI: 1.5-4.4; p = 0.002) when compared
to those with high adherence to a MeDiet/HighMF/HighCRF, after adjustments for
potential confounders. In conclusion, our findings showed that, regardless of the
MeDiet status, adolescents with low MF and low CRF cumulatively, presented the
highest cardiovascular disease risk. Therefore, these findings suggest that the
combination of these two fitness components may be beneficial to
adolescents’ cardiometabolic profile, independent of MeDiet behaviour.
PMID- 29941784
TI - Estimation of Mercury Emission from Incineration of Extracted Teeth with Dental
Amalgam Fillings in South Korea.
AB - This study is aimed to estimate the levels of mercury emission related to amalgam
fillings at dental institutions in order to provide basic data for establishing a
management protocol for extracted mercury-containing amalgam fillings. We
conducted a cross-sectional study at a dental clinic of a general hospital (City
of Daegu), a dental hospital (City of Daegu), and five private dental clinics
(one in the South and four in the North Gyeongsang Province). The extracted
anterior and posterior teeth (N = 1208) were separated, and the amalgam filling
rate of the posterior teeth was assessed. After cutting out the amalgam from
filled posterior teeth, the weight of the amalgam was measured, and the estimated
mercury emission was calculated based on the equation, where annual number of
extracted posterior teeth × amalgam filling rate (%) × mean amalgam
weight (g) × 0.5 (the proportion of mercury in amalgam). We found that
48.86 kg (95% confidence interval [CI] 41.53-58.63 kg) of mercury had been
incinerated along with the extracted teeth. After applying the dental institution
weights, the estimated amount of mercury was 42.53 kg (95% CI 34.11-52.17 kg).
The amount of mercury incinerated with extracted posterior teeth at Korean dental
institutions is therefore about 42.53-48.86 kg/year.
PMID- 29941786
TI - Relationship between Inflammatory and Biological Markers and Lung Cancer.
AB - We seek to define inflammatory markers, lipid and protein profiles that may aid
in distinguishing lung cancer cases from those who are healthy and to determine
the relationships between these levels and cancer stage and cell type. Lung
cancer patients (n = 140, Group 1) and healthy cases (n = 50, Group 2) were
enrolled. We retrieved platelet, platelet-associated markers (plateletcrit (PCT),
mean platelet volume (MPV), platelet distribution width (PDW)),
neutrophil/lymphocyte ratio-NLR, platelet/lymphocyte ratio-PLR, lipids (total
cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL),
very low density lipoprotein (VLDL), triglycerides), proteins (total protein (TP)
and albumin), and C-reactive protein (CRP) from electronic records and compared
the data from lung cancer patients with those from healthy controls. Platelet,
PCT, neutrophil, NLR, PLR, triglycerides, VLDL, and CRP levels were significantly
higher in Group 1 compared with Group 2. MPV, lymphocyte, albumin, and HDL levels
were significantly lower in Group 1 compared with Group 2. No significant
relationship was evident between histopathological types and the level of any
marker. Compared to those with early-stage cancer, changes in marker levels in
those with advanced-stage cancer were statistically significant. CRP and NLR were
significantly higher; albumin and HDL were lower in metastatic patients. We found
that platelet, PCT, NLR and PLR, albumin, HDL, and CRP levels aided in lung
cancer diagnosis and the detection of late-stage disease. Furthermore, these
inflammatory and biological markers are thought to be particularly useful in
following the severity of lung cancer.
PMID- 29941785
TI - Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure.
AB - The ductus arteriosus (DA) connects the main pulmonary artery and the aorta in
fetal circulation and closes spontaneously within days after birth in normal
infants. Abnormal patent DA (PDA) causes morbidities and mortality, especially in
preterm infants. Closure of the DA is a complex interactive process involving two
events: functional and anatomic closure. Functional closure by smooth muscle
contraction was achieved through the regulatory factors of vaso-reactivity. These
factors include oxygen sensing system, glutamate, osmolality, prostaglandin E2,
nitric oxide, and carbon monoxide. Anatomic closure by vascular remodeling
involved several vascular components including endothelium, extracellular matrix,
smooth muscle cells, and intraluminal blood cells. Despite advances in
understanding of PDA pathogenesis, the molecular mechanism for regulation of DA
closure is complex and not fully understood. In this article we review recent
evidence regarding the molecular mechanisms of DA closure.
PMID- 29941787
TI - The Reprimo Gene Family: A Novel Gene Lineage in Gastric Cancer with Tumor
Suppressive Properties.
AB - The reprimo (RPRM) gene family is a group of single exon genes present
exclusively within the vertebrate lineage. Two out of three members of this
family are present in humans: RPRM and RPRM-Like (RPRML). RPRM induces cell cycle
arrest at G2/M in response to p53 expression. Loss-of-expression of RPRM is
related to increased cell proliferation and growth in gastric cancer. This
evidence suggests that RPRM has tumor suppressive properties. However, the
molecular mechanisms and signaling partners by which RPRM exerts its functions
remain unknown. Moreover, scarce studies have attempted to characterize RPRML,
and its functionality is unclear. Herein, we highlight the role of the RPRM gene
family in gastric carcinogenesis, as well as its potential applications in
clinical settings. In addition, we summarize the current knowledge on the
phylogeny and expression patterns of this family of genes in embryonic zebrafish
and adult humans. Strikingly, in both species, RPRM is expressed primarily in the
digestive tract, blood vessels and central nervous system, supporting the use of
zebrafish for further functional characterization of RPRM. Finally, drawing on
embryonic and adult expression patterns, we address the potential relevance of
RPRM and RPRML in cancer. Active investigation or analytical research in the
coming years should contribute to novel translational applications of this poorly
understood gene family as potential biomarkers and development of novel cancer
therapies.
PMID- 29941788
TI - Pallidal Stimulation Modulates Pedunculopontine Nuclei in Parkinson's Disease.
AB - BACKGROUND: In advanced Parkinson’s disease, the pedunculopontine nucleus
region is thought to be abnormally inhibited by gamma-aminobutyric acid (GABA)
ergic inputs from the over-active globus pallidus internus. Recent attempts to
boost pedunculopontine nucleus function through deep brain stimulation are
promising, but suffer from the incomplete understanding of the physiology of the
pedunculopontine nucleus region. METHODS: Local field potentials of the
pedunculopontine nucleus region and the globus pallidus internus were recorded
and quantitatively analyzed in a patient with Parkinson’s disease. In
particular, we compared the local field potentials from the pedunculopontine
nucleus region at rest and during deep brain stimulation of the globus pallidus
internus. RESULTS: At rest, the spectrum of local field potentials in the globus
pallidus internus was mainly characterized by delta-theta and beta frequency
activity whereas the spectrum of the pedunculopontine nucleus region was
dominated by activity only in the delta and theta band. High-frequency deep brain
stimulation of the globus pallidus internus led to increased theta activity in
the pedunculopontine nucleus region and enabled information exchange between the
left and right pedunculopontine nuclei. Therefore, Conclusions: When applying
deep brain stimulation in the globus pallidus internus, its modulatory effect on
pedunculopontine nucleus physiology should be taken into account.
PMID- 29941789
TI - Fluorinated Graphene Prepared by Direct Fluorination of N, O-Doped Graphene
Aerogel at Different Temperatures for Lithium Primary Batteries.
AB - Fluorinated graphene (FG) has been a star material as a new derivative of
graphene. In this paper, a series of fluorinated graphene materials are prepared
by using N, O-doped graphene aerogel as precursor via a direct fluorination
method, and the effect of fluorination temperature on the FG structure is
investigated. The prepared FG samples are systematically characterized by
scanning and transmission electron microscopy, X-ray photoelectron spectroscopy,
X-ray diffraction, Fourier transform infrared spectroscopy, and Raman
spectroscopy. It is found that the structure of FG, including features such as
layer size, chemical composition, chemical bond state of the component elements,
etc., is significantly related to the fluorination temperature. With the change
of the fluorination temperature, fluorine atoms enter the graphene framework by a
substitution process of the N, O-containing groups, including residual phenol,
ether, carbonyl groups, or C-N groups, and the addition to CC bonds, subsequently
forming a fluoride with different fluorine contents. The fluorine content
increases as the fluorination temperature increases from 200 °C to 300
°C, but decreases at a fluorination temperature of 350 °C due to the
decomposition of the fluorinated graphene. The prepared FG samples are used as
cathode material for lithium primary batteries. The FG sample prepared at 300
°C gives a high specific capacity of 632 mAh g−1 and a discharge
plateau of 2.35 V at a current density of 10 mA g−1, corresponding to a
high energy density of 1485 Wh kg−1.
PMID- 29941791
TI - Fiber Laser Welding of Fuel Cladding and End Plug Made of La2O3 Dispersion
Strengthened Molybdenum Alloy.
AB - The study investigated the laser lap welding of fuel cladding and end plug made
of molybdenum (Mo) alloy. The research results showed that the tensile strength
of the welded joint when a weld was located at the Mo tube was significantly
larger than that at the fit-up gap between the fuel cladding and end plug.
Moreover, preheating can also greatly increase the tensile strength of the lap
joint. The weld zone was filled with bulky coarse columnar crystal structures
while there were numerous coarse recrystallized structures in the heat affected
zone (HAZ). The weld zone and HAZ were both subjected to a significant softening.
The tensile strength and elongation rate of fuel cladding made of Mo alloy were
about 750 MPa and 36.7%, respectively. The welded joint did not undergo any
plastic deformation during the tensile process and presented a brittle fracture.
Under the optimum processing conditions, the tensile strength of the welded joint
reached 617 MPa, taking up 82.3% that of the base metal. The results of
composition analysis indicated that there was only Mo inside the columnar
crystals in weld zone while significant oxygen segregation was observed at the
grain boundary. This was the main reason causing that the strength of welded
joint was lower than that of the base metal. Additionally, under the optimum
processing conditions, there were numerous slender columnar crystals on the cross
section of the joint entering the weld zone in fuel cladding side from that in
end plug side where the crystals were nucleated and grew upwards. The analysis
results suggested that the presence of these slender columnar crystals crossing
the interface between fuel cladding and end plug was favorable for improving the
capacity of the joint for bearing the shear loads.
PMID- 29941790
TI - The Positive Role of Curcumin-Loaded Salmon Nanoliposomes on the Culture of
Primary Cortical Neurons.
AB - Curcumin (diferuloylmethane) is a natural bioactive compound with many health
promoting benefits. However, its poor water solubility and bioavailability has
limited curcumin’s biomedical application. In the present study, we
encapsulated curcumin into liposomes, formed from natural sources (salmon
lecithin), and characterized its encapsulation efficiency and release profile.
The proposed natural carriers increased the solubility and the bioavailability of
curcumin. In addition, various physico-chemical properties of the developed soft
nanocarriers with and without curcumin were studied. Nanoliposome-encapsulated
curcumin increased the viability and network formation in the culture of primary
cortical neurons and decreased the rate of apoptosis.
PMID- 29941793
TI - The SDN Approach for the Aggregation/Disaggregation of Sensor Data.
AB - In many Internet of Things (IoT) applications, large numbers of small sensor data
are delivered in the network, which may cause heavy traffics. To reduce the
number of messages delivered from the sensor devices to the IoT server, a
promising approach is to aggregate several small IoT messages into a large packet
before they are delivered through the network. When the packets arrive at the
destination, they are disaggregated into the original IoT messages. In the
existing solutions, packet aggregation/disaggregation is performed by software at
the server, which results in long delays and low throughputs. To resolve the
above issue, this paper utilizes the programmable Software Defined Networking
(SDN) switch to program quick packet aggregation and disaggregation.
Specifically, we consider the Programming Protocol-Independent Packet Processor
(P4) technology. We design and develop novel P4 programs for aggregation and
disaggregation in commercial P4 switches. Our study indicates that packet
aggregation can be achieved in a P4 switch with its line rate (without extra
packet processing cost). On the other hand, to disaggregate a packet that
combines N IoT messages, the processing time is about the same as processing N
individual IoT messages. Our implementation conducts IoT message aggregation at
the highest bit rate (100 Gbps) that has not been found in the literature. We
further propose to provide a small buffer in the P4 switch to significantly
reduce the processing power for disaggregating a packet.
PMID- 29941792
TI - Contemporary Dietary Intake: Too Much Sodium, Not Enough Potassium, yet
Sufficient Iodine: The SALMEX Cohort Results.
AB - Initiatives to reduce sodium intake are encouraged globally, yet there is concern
about compromised iodine intake supplied through salt. The aim of the present
study was to determine baseline sodium, potassium, and iodine intake in a sample
of workers from our Institution in Mexico City (SALMEX Cohort). Methods. From a
cohort of 1009 workers, appropriate 24-h urine and three-day dietary recall was
collected in a sample of 727 adult subjects for assessment of urinary sodium,
potassium, and iodine concentrations. Median urinary iodine excretion (UIE) was
compared across categories of sodium intake of <2, 2-3.6, and ≥3.6 g/day.
Results. Average sodium intake was 3.49 +/- 1.38 g/day; higher in men than women
(4.14 vs. 3.11 g/day, p ≤0.001). Only 10.6% of the population had sodium
intake within the recommended range (<2 g/day); 45.4% had high (2-3.6 g/day) and
44% had excessive intake (>3.6 g/day). Average urinary Na/K ratio was 3.15 +/-
1.22 (ideal < 1), higher in men (3.42 vs. 3.0, p ≤ 0.001). The multivariate
analysis showed that sodium intake was associated with age (p = 0.03), male sex
(p < 0.001), caloric intake (p = 0.002), UKE (p < 0.001) and BMI (p < 0.001).
Median iodine intake was 286.7 µg/day (IQR 215-370 µg/day). Less than
2% of subjects had iodine intake lower than recommended for adults (95
µg/day); 1.3% of subjects in the recommended range of salt intake had low
iodine intake. There is a direct relationship between iodine and sodium urinary
excretion (r = 0.57, p < 0.0001). Conclusions. In the studied population, there
was an excessive sodium intake and an imbalance between sodium and potassium
intake. Only 10.6% of the population had sodium intake within the recommended
values, but iodine intake in this group appears to be adequate.
PMID- 29941794
TI - Predicted Mercury Soil Concentrations from a Kriging Approach for Improved Human
Health Risk Assessment.
AB - Health-risks from contaminated soils are assessed all over the world. An aspect
that many risk assessments share is the heterogeneity in the distribution of
contaminants. In a preceding study, we assessed potential health-risks for
mothers and children living on mercury-contaminated soils in Switzerland using
human biomonitoring-values (HBM) and soil samples. We assessed 64 mothers and 107
children who had resided in a defined area for at least 3 months. HBM
concentrations for mercury in urine and hair were measured, a detailed
questionnaire was administered for each individual, and more than 4000 individual
mercury soil values were obtained in 2015. In this study, we aimed at
investigating possible associations of mercury soil- and HBM-values by re
analyzing our data, using predictions of the mercury concentrations at the exact
location of the participant’s homes with a kriging approach. Although
kriging proved to be a useful method to predict mercury soil concentrations, we
did not detect an association between mercury soil- and HBM-values, in agreement
with earlier findings. Benefits of geostatistical methods seem to be limited in
the context of our study. Conclusions made in our preceding study about potential
health risks for the residential population are robust and not altered by the
current study.
PMID- 29941795
TI - Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal
Inflammation on Brain and Depression.
AB - The human gastrointestinal tract is inhabited by trillions of commensal bacteria
collectively known as the gut microbiota. Our recognition of the significance of
the complex interaction between the microbiota, and its host has grown
dramatically over the past years. A balanced microbial community is a key
regulator of the immune response, and metabolism of dietary components, which in
turn, modulates several brain processes impacting mood and behavior.
Consequently, it is likely that disruptions within the composition of the
microbiota would remotely affect the mental state of the host. Here, we discuss
how intestinal bacteria and their metabolites can orchestrate gut-associated
neuroimmune mechanisms that influence mood and behavior leading to depression. In
particular, we focus on microbiota-triggered gut inflammation and its
implications in shifting the tryptophan metabolism towards kynurenine
biosynthesis while disrupting the serotonergic signaling. We further investigate
the gaps to be bridged in this exciting field of research in order to clarify our
understanding of the multifaceted crosstalk in the microbiota-gut-brain
interphase, bringing about novel, microbiota-targeted therapeutics for mental
illnesses.
PMID- 29941796
TI - Insights into Macrophage Heterogeneity and Cytokine-Induced Neuroinflammation in
Major Depressive Disorder.
AB - Over 350 million individuals suffer from depression, a psychiatric illness
classified as major depressive disorder (MDD) with symptoms that include a loss
of interest or pleasure in life accompanied by depressed mood. The present
understanding of major depressive disorder does not encompass a systematic
characterization of the neurobiological processes that drive the behavioral
physiology in patients diagnosed with major depressive disorder. Psychiatric
illness is a complex intersection between genetics, physiology, immunology and
environmental stress. The increased attention to the relevance of depression has
led to new discoveries that highlight the biological significance of
‘neuroinflammation’ and immunity underlying a spectrum of psychiatric
illnesses. The process of neuroinflammation involves sentinel immune cells in the
central nervous system (CNS). The activation and polarization of microglia, CNS
resident macrophages, modulates the production and secretion of pro-inflammatory
cytokines implicated in the etiology of major depressive disorder, and this
phenomenon has been aptly titled the ‘macrophage theory of
depression’. Of particular interest are three hallmark cytokines, IL-6,
TNFα and IL-1β, which have been studied extensively in basic research,
cell-receptor signaling and drug development. The field of inflammasome-mediated
neuroinflammation is an emerging area of MDD research that is providing new
cellular insight into how macrophages mechanistically support cytokine-associated
neuropathology, particularly in the case of IL-1β-associated inflammation in
MDD. With the increasing number of individuals identified with depression, a
comprehensive understanding of macrophage-cytokine signaling pathways in the CNS
in depression is necessary for developing effective anti-depressant therapeutics.
PMID- 29941797
TI - Reelin Haploinsufficiency and Late-Adolescent Corticosterone Treatment Induce
Long-Lasting and Female-Specific Molecular Changes in the Dorsal Hippocampus.
AB - Reelin depletion and stress seem to affect similar pathways including GABAergic
and glutamatergic signaling and both are implicated in psychiatric disorders in
late adolescence/early adulthood. The interaction between reelin depletion and
stress, however, remains unclear. To investigate this, male and female
heterozygous reelin mice (HRM) and wildtype (WT) controls were treated with the
stress hormone, corticosterone (CORT), during late adolescence to simulate
chronic stress. Glucocorticoid receptors (GR), N-methyl-d-aspartate receptor
(NMDAr) subunits, glutamic acid decarboxylase (GAD67) and parvalbumin (PV) were
measured in the hippocampus and the prefrontal cortex (PFC) in adulthood. While
no changes were seen in male mice, female HRM showed a significant reduction in
GR expression in the dorsal hippocampus. In addition, CORT reduced GR levels as
well as GluN2B and GluN2C subunits of NMDAr in the dorsal hippocampus in female
mice only. CORT furthermore reduced GluN1 levels in the PFC of female mice. The
combined effect of HRM and CORT treatment appeared to be additive in terms of GR
expression in the dorsal hippocampus. Female-specific CORT-induced changes were
associated with overall higher circulating CORT levels in female compared to male
mice. This study shows differential effects of reelin depletion and CORT
treatment on GR and NMDAr protein expression in male and female mice, suggesting
that females are more susceptible to reelin haploinsufficiency as well as late
adolescent stress. These findings shed more light on female-specific
vulnerability to stress and have implications for stress-associated mental
illnesses with a female bias including anxiety and major depression.
PMID- 29941798
TI - Sulfate-Reducing Naphthalene Degraders Are Picky Eaters.
AB - Polycyclic aromatic hydrocarbons (PAHs) are common organic contaminants found in
anoxic environments. The capacity for PAH biodegradation in unimpacted
environments, however, has been understudied. Here we investigate the enrichment,
selection, and sustainability of a microbial community from a pristine
environment on naphthalene as the only amended carbon source. Pristine coastal
sediments were obtained from the Jacques Cousteau National Estuarine Research
Reserve in Tuckerton, New Jersey, an ecological reserve which has no direct input
or source of hydrocarbons. After an initial exposure to naphthalene, primary
anaerobic transfer cultures completely degraded 500 µM naphthalene within
139 days. Subsequent transfer cultures mineralized naphthalene within 21 days
with stoichiometric sulfate loss. Enriched cultures efficiently utilized only
naphthalene and 2-methylnaphthalene from the hydrocarbon mixtures in crude oil.
To determine the microorganisms responsible for naphthalene degradation, stable
isotope probing was utilized on cultures amended with fully labeled 13C
naphthalene as substrate. Three organisms were found to unambiguously synthesize
13C-DNA from 13C-naphthalene within 7 days. Phylogenetic analysis revealed that
16S rRNA genes from two of these organisms are closely related to the known
naphthalene degrading isolates NaphS2 and NaphS3 from PAH-contaminated sites. A
third 16S rRNA gene was only distantly related to its closest relative and may
represent a novel naphthalene degrading microbe from this environment.
PMID- 29941799
TI - Nanoscale Biosensors Based on Self-Propelled Objects.
AB - This review provides a comprehensive overview of the latest developments (2016
2018 period) in the nano and micromotors field for biosensing applications. Nano
and micromotor designs, functionalization, propulsion modes and transduction
mechanism are described. A second important part of the review is devoted to
novel in vitro and in vivo biosensing schemes. The potential and future prospect
of such moving nanoscale biosensors are given in the conclusions.
PMID- 29941800
TI - Understanding the Influence of Interface Morphology on the Performance of
Perovskite Solar Cells.
AB - In recent years, organo-halide perovskite solar cells have garnered a surge of
interest due to their high performance and low-cost fabrication processing. Owing
to the multilayer architecture of perovskite solar cells, interface not only has
a pivotal role to play in performance, but also influences long-term stability.
Here we have employed diverse morphologies of electron selective layer (ESL) to
elucidate charge extraction behavior in perovskite solar cells. The TiO2
mesoporous structure (three-dimensional) having varied thickness, and nanocolumns
(1-dimensional) with tunable length were employed. We found that a TiO2 electron
selective layer with thickness of about c.a. 100 nm, irrespective of its
microstructure, was optimal for efficient charge extraction. Furthermore, by
employing impedance spectroscopy at different excitation wavelengths, we studied
the nature of recombination and its dependence on the charge generation profile,
and results showed that, irrespective of the wavelength region, the fresh devices
do not possess any preferential recombination site, and recombination process is
governed by the bulk of the perovskite layer. Moreover, depending on the type of
ESL, a different recombination mechanism was observed that influences the final
behavior of the devices.
PMID- 29941801
TI - UAVs, Hyperspectral Remote Sensing, and Machine Learning Revolutionizing Reef
Monitoring.
AB - Recent advances in unmanned aerial system (UAS) sensed imagery, sensor
quality/size, and geospatial image processing can enable UASs to rapidly and
continually monitor coral reefs, to determine the type of coral and signs of
coral bleaching. This paper describes an unmanned aerial vehicle (UAV) remote
sensing methodology to increase the efficiency and accuracy of existing
surveillance practices. The methodology uses a UAV integrated with advanced
digital hyperspectral, ultra HD colour (RGB) sensors, and machine learning
algorithms. This paper describes the combination of airborne RGB and
hyperspectral imagery with in-water survey data of several types in-water survey
of coral under diverse levels of bleaching. The paper also describes the
technology used, the sensors, the UAS, the flight operations, the processing
workflow of the datasets, the methods for combining multiple airborne and in
water datasets, and finally presents relevant results of material classification.
The development of the methodology for the collection and analysis of airborne
hyperspectral and RGB imagery would provide coral reef researchers, other
scientists, and UAV practitioners with reliable data collection protocols and
faster processing techniques to achieve remote sensing objectives.
PMID- 29941802
TI - A Hetero-Photoautotrophic Two-Stage Cultivation Process for Production of
Fucoxanthin by the Marine Diatom Nitzschia laevis.
AB - There is currently much interest in fucoxanthin due to its broad beneficial
health effects. The major commercial source of fucoxanthin is marine seaweed,
which has many shortcomings, and has thus restricted its large-scale production
and more diversified applications. In this study, growth characteristics and
fucoxanthin accumulation were evaluated to explore the potential of the marine
diatom Nitzschia laevis in fucoxanthin production. The results suggested that
heterotrophic culture was more effective for cell growth, while the mixotrophic
culture was favorable for fucoxanthin accumulation. A two-stage culture strategy
was consequently established. A model of exponential fed-batch culture led to a
biomass concentration of 17.25 g/L. A mix of white and blue light significantly
increased fucoxanthin content. These outcomes were translated into a superior
fucoxanthin productivity of 16.5 mg/(L·d), which was more than 2-fold of
the best value reported thus far. The culture method established herein therefore
represents a promising strategy to boost fucoxanthin production in N. laevis,
which might prove to be a valuable natural source of commercial fucoxanthin.
PMID- 29941803
TI - Daily Intake Estimation for Young Children's Ingestion of Residential Dust and
Soils Contaminated with Chlorpyrifos and Cypermethrin in Taiwan.
AB - We estimated the daily intakes of chlorpyrifos and cypermethrin via ingestion of
indoor dust and outdoor soils using the Stochastic Human Exposure and Dose
Simulation Model on a probabilistic approach for Taiwanese young children.
Variables for the estimation, such as concentration, ingestion rate, and body
weight, were adopted from previous studies. Monte Carlo simulation was performed
with 1,000,000 iterations to simulate a single daily intake, which was shown in
terms of percentage of the Acceptable Daily Intake (ADI) of either insecticide.
The daily intakes are minimal with a 99% probability, but go up steeply at the
99.9th percentile (13.1% and 20.0% of the ADIs of chlorpyrifos and cypermethrin,
respectively). The sensitivity analysis indicates that concentration is the most
determinant variable for daily intake estimation, suggesting that high intakes
may occur when insecticide concentrations are elevated. Compared to the data of
daily intakes via dietary ingestion of vegetables derived from a previous study,
the estimated non-dietary intakes are negligible until reaching the highest
percentile. Consequently, the non-dietary ingestion exposure to either
insecticide is commonly low for young children in Taiwan’s homes, unless
high contamination (e.g., indoor insecticide application) occurs in the
environment. Care has to be taken to avoid high contamination indoors.
PMID- 29941804
TI - Ambient Sensors for Elderly Care and Independent Living: A Survey.
AB - Elderly care at home is a matter of great concern if the elderly live alone,
since unforeseen circumstances might occur that affect their well-being.
Technologies that assist the elderly in independent living are essential for
enhancing care in a cost-effective and reliable manner. Elderly care applications
often demand real-time observation of the environment and the resident’s
activities using an event-driven system. As an emerging area of research and
development, it is necessary to explore the approaches of the elderly care system
in the literature to identify current practices for future research directions.
Therefore, this work is aimed at a comprehensive survey of non-wearable (i.e.,
ambient) sensors for various elderly care systems. This research work is an
effort to obtain insight into different types of ambient-sensor-based elderly
monitoring technologies in the home. With the aim of adopting these technologies,
research works, and their outcomes are reported. Publications have been included
in this survey if they reported mostly ambient sensor-based monitoring
technologies that detect elderly events (e.g., activities of daily living and
falls) with the aim of facilitating independent living. Mostly, different types
of non-contact sensor technologies were identified, such as motion, pressure,
video, object contact, and sound sensors. Besides, multicomponent technologies
(i.e., combinations of ambient sensors with wearable sensors) and smart
technologies were identified. In addition to room-mounted ambient sensors,
sensors in robot-based elderly care works are also reported. Research that is
related to the use of elderly behavior monitoring technologies is widespread, but
it is still in its infancy and consists mostly of limited-scale studies. Elderly
behavior monitoring technology is a promising field, especially for long-term
elderly care. However, monitoring technologies should be taken to the next level
with more detailed studies that evaluate and demonstrate their potential to
contribute to prolonging the independent living of elderly people.
PMID- 29941805
TI - Ventilation and Air Quality in Student Dormitories in China: A Case Study during
Summer in Nanjing.
AB - The Air quality in student dormitories can have a major impact on the health of
millions of students in China. This study aims to investigate the ventilation and
air quality in student dormitories. Questionnaire survey was conducted in eight
dormitory buildings and field measurements were conducted in one dormitory during
the summer in Nanjing. The survey result reveals that most students thought the
indoor and outdoor air quality was neutral and the correlation between indoor and
outdoor perceived air quality is statistically significant. There are few indoor
PM2.5 and ozone sources in dormitories and natural ventilation is the most common
form of ventilation. However, there is no statistically significant correlation
between window opening behaviors and the perceptions of indoor and outdoor air
quality. The field measurement result shows the measured I/O ratios of PM2.5 and
ozone over 37 days are in the range of 0.42-0.79 and 0.21-1.00, respectively. The
I/O ratios for PM2.5 and ozone are 0.49 +/- 0.05 and 0.26 +/- 0.05 in the case of
the window being closed, and the I/O ratios for PM2.5 and ozone are 0.65 +/- 0.08
and 0.50 +/- 0.15 in the case of the window being open. The outdoor and indoor
ozone concentrations show pronounced diurnal periodic variations, while the PM2.5
concentrations do not. Finally, recommended open/close window strategies are
discussed to reduce indoor pollutant levels. Understanding the indoor/outdoor
PM2.5 and ozone concentrations in different window patterns can be a guidance to
preventing high indoor PM2.5 and ozone exposure in student dormitories.
PMID- 29941806
TI - Immunogold Nanoparticles for Rapid Plasmonic Detection of C. sakazakii.
AB - Cronobacter sakazakii is a foodborne pathogen that can cause a rare, septicemia,
life-threatening meningitis, and necrotizing enterocolitis in infants. In
general, standard methods for pathogen detection rely on culture, plating, colony
counting and polymerase chain reaction DNA-sequencing for identification, which
are time, equipment and skill demanding. Recently, nanoparticle- and surface
based immunoassays have increasingly been explored for pathogen detection. We
investigate the functionalization of gold nanoparticles optimized for
irreversible and specific binding to C. sakazakii and their use for spectroscopic
detection of the pathogen. We demonstrate how 40-nm gold nanoparticles grafted
with a poly(ethylene glycol) brush and functionalized with polyclonal antibodies
raised against C. sakazakii can be used to specifically target C. sakazakii. The
strong extinction peak of the Au nanoparticle plasmon polariton resonance in the
optical range is used as a label for detection of the pathogens. Individual
binding of the nanoparticles to the C. sakazakii surface is also verified by
transmission electron microscopy. We show that a high degree of surface
functionalization with anti-C. sakazakii optimizes the detection and leads to a
detection limit as low as 10 CFU/mL within 2 h using a simple cuvette-based UV
Vis spectrometric readout that has great potential for further optimization.
PMID- 29941807
TI - Electrochemical and Stress Corrosion Mechanism of Submarine Pipeline in Simulated
Seawater in Presence of Different Alternating Current Densities.
AB - In this study, electrochemical measurements, immersion tests, and slow strain
rate tensile (SSRT) tests were applied to investigate the electrochemical and
stress corrosion cracking (SCC) behavior of X70 steel in simulated seawater with
the interference of different alternating current (AC) densities. The results
indicate that AC significantly strengthens the cathodic reaction, especially the
oxygen reduction reaction. Simultaneously, hydrogen evolution reaction occurs
when the limiting diffusion current density of oxygen reaches, and thus, icorr
sharply increases with the increase in AC density. Additionally, when AC is
imposed, the X70 steel exhibits higher SCC susceptibility in the simulated
seawater, and the susceptibility increases with the increasing AC density. The
SCC mechanism is controlled by both anodic dissolution (AD) and hydrogen
embrittlement (HE) with the interference of AC.
PMID- 29941808
TI - Online Structural-Health Monitoring of Glass Fiber-Reinforced Thermoplastics
Using Different Carbon Allotropes in the Interphase.
AB - An electromechanical response behavior is realized by nanostructuring the glass
fiber interphase with different highly electrically conductive carbon allotropes
like carbon nanotubes (CNT), graphene nanoplatelets (GNP), or conductive carbon
black (CB). The operational capability of these multifunctional glass fibers for
an online structural-health monitoring is demonstrated in endless glass fiber
reinforced polypropylene. The electromechanical response behavior, during a
static or dynamic three-point bending test of various carbon modifications, shows
qualitative differences in the signal quality and sensitivity due to the
different aspect ratios of the nanoparticles and the associated electrically
conductive network densities in the interphase. Depending on the embedding
position within the glass fiber-reinforced composite compression, shear and
tension loadings of the fibers can be distinguished by different characteristics
of the corresponding electrical signal. The occurrence of irreversible signal
changes during the dynamic loading can be attributed to filler reorientation
processes caused by polymer creeping or by destruction of electrically conductive
paths by cracks in the glass fiber interphase.
PMID- 29941809
TI - Facile Preparation of Metal-Organic Framework (MIL-125)/Chitosan Beads for
Adsorption of Pb(II) from Aqueous Solutions.
AB - In this study, novel composite titanium-based metal-organic framework (MOF) beads
were synthesized from titanium based metal organic framework MIL-125 and chitosan
(CS) and used to remove Pb(II) from wastewater. The MIL-125-CS beads were
prepared by combining the titanium-based MIL-125 MOF and chitosan using a
template-free solvothermal approach under ambient conditions. The surface and
elemental properties of these beads were analyzed using scanning electron
microscopy, Fourier transform infrared and X-ray photoelectron spectroscopies, as
well as thermal gravimetric analysis. Moreover, a series of experiments designed
to determine the influences of factors such as initial Pb(II) concentration, pH,
reaction time and adsorption temperature was conducted. Notably, it was found
that the adsorption of Pb(II) onto the MIL-125-CS beads reached equilibrium in
180 min to a level of 407.50 mg/g at ambient temperature. In addition, kinetic
and equilibrium experiments provided data that were fit to the Langmuir isotherm
model and pseudo-second-order kinetics. Furthermore, reusability tests showed
that MIL-125-CS retained 85% of its Pb(II)-removal capacity after five reuse
cycles. All in all, we believe that the developed MIL-125-CS beads are a
promising adsorbent material for the remediation of environmental water polluted
by heavy metal ions.
PMID- 29941810
TI - The Protective Role of Astaxanthin for UV-Induced Skin Deterioration in Healthy
People-A Randomized, Double-Blind, Placebo-Controlled Trial.
AB - Skin is a major safeguard tissue in humans. Because biological barrier function
is deteriorated by several kinds of stresses including exposure to ultra-violet
(UV) rays, the protection and treatment of skin conditions by dietary supplements
are important. We therefore evaluated the effects of dietary supplementation with
an algal food-derived antioxidant, astaxanthin, on UV-induced skin deterioration.
Twenty-three healthy Japanese participants were recruited to a 10-week double
blind placebo-controlled study. They were assigned to the astaxanthin group
supplemented with a capsule containing 4 mg of astaxanthin or the placebo group.
To assess the protective role of astaxanthin for UV-induced skin deterioration,
we determined the minimal erythema dose (MED) and analyzed UV-induced changes of
moisture and transepidermal water loss (TEWL) at baseline and after 9 weeks of
supplementation. Subjective skin conditions were assessed by the visual analog
scale. The astaxanthin group showed increased MED compared with placebo. In
addition, the astaxanthin group had a reduced loss of skin moisture in the
irradiated area compared with placebo. Subjective skin conditions for
“improvement of rough skin” and “texture” in non
irradiated areas were significantly improved by astaxanthin. Astaxanthin seems
protective against UV-induced skin deterioration and helps maintain healthy skin
in healthy people.
PMID- 29941811
TI - Effect of an Intervention Program Based on Active Video Games and Motor Games on
Health Indicators in University Students: A Pilot Study.
AB - (1) Background: High levels of physical inactivity caused by sedentary digital
screen leisure constitute one of the main causes of the high levels of obesity
observed in today’s society; (2) Methods: The present study aims to analyse
the effect of a 12-week intervention program based on the application of active
video games and motor games on health status indicators, problematic use of video
games, and resilience capacity in university students. Besides, the content
blocks of the Physical Education (PE) field are worked on through these devices,
revealing their potential as an Information and Communications Technology (ICT)
resource. A longitudinal study with a pre-experimental design with pretest
posttest measurements in a single group (n = 47) was performed, using as main
instruments a Tanita TBF300® bioimpedance scale, the 20mSRT test for maximum
oxygen consumption (VO2max), the Adherence to a Mediterranean Diet Test (KIDMED),
the Questionnaire for Experiences Related to Video games (QERV) and the Connor
Davidson Resilience Scale (CD-RISC); (3) Results: The main results were a
discrete improvement in the percentage of fat mass and VO2max, representing a
small effect size in both cases. The quality of the diet followed and the
confidence and tolerance for adversity as a resilience factor were also improved,
representing a medium size effect for this last variable; (4) Conclusions:
Despite the limitations of this study as it does not have a control group, the
main conclusions are that active video games and motor games can be a
motivational resource to follow an active lifestyle, helping to improve health
status indicators in young adults.
PMID- 29941812
TI - Effect of Vipera ammodytes ammodytes Snake Venom on the Human Cytokine Network.
AB - Local inflammation is a well-known symptom of envenomation by snakes of the
family Viperidae, attributed primarily to the phospholipase A2s,
metalloproteinases and L-amino acid oxidases contained in their venom. The
inflammatory effect of snake venoms has been associated with a marked increase of
the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α. To determine the
impact of Vipera ammodytes ammodytes snake venom on the expression of
inflammation-related genes, we incubated human U937 monocyte cells with dilutions
of snake venom. Gene expression was quantified for 28 different genes using a
TaqMan® Array Human Cytokine Network 96-well Plate in a RT-qPCR system. Our
results have demonstrated that 1.0 μg/mL Vipera ammodytes ammodytes venom
solution induces a notable change in the expression of several cytokine network
genes. Among the upregulated genes, there were several that encode interleukins,
interferons, and tumor necrosis factors. We further report the downregulation of
three interleukin-related genes. Our findings come as supportive information for
the known complex effect of snake venoms on the human cytokine network. It also
provides relevant new information regarding the expression of genes that have not
been previously associated with the effect of snake venoms.
PMID- 29941813
TI - Effect of Phosphate-Solubilizing Bacteria on the Mobility of Insoluble Cadmium
and Metabolic Analysis.
AB - Phosphate-solubilizing bacteria (PSB) can promote plant growth by dissolving
insoluble phosphate. Therefore, PSB may have the potential to improve the
mobility of heavy metals in soils and enhance phytoextraction. This study
isolated a few PSB strains that could dissolve CdCO3 and solid Cd in soil. Two
typical PSB, namely, high- and low-Cd-mobilizing PSB (Pseudomonas fluorescens gim
3 and Bacillus cereus qh-35, respectively), were selected to analyze the
metabolic profiles, metabolic pathways, and mechanisms of mobilization of
insoluble Cd. A total of 34 metabolites secreted by the two PSB strains were
identified. Gluconic acid was the main contributor to Cd dissolution (42.4%) in
high-Cd-mobilizing PSB. By contrast, gluconic acid was not secreted in low-Cd
mobilizing PSB. Metabolic pathway analysis showed that gluconic acid was produced
by the peripheral direct oxidation pathway. Hence, PSB with peripheral direct
oxidation pathway were likely to have high-Cd-mobilizing capacity.
PMID- 29941815
TI - Boldine Improves Kidney Damage in the Goldblatt 2K1C Model Avoiding the Increase
in TGF-beta.
AB - Boldine, a major aporphine alkaloid found in the Chilean boldo tree, is a potent
antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of
kidney damage in renovascular hypertension (RVH). The activation of the renin
angiotensin system (RAS) is crucial to the development and progression of
hypertensive renal damage and TGF-β is closely associated with the
activation of RAS. In the present study, we assessed the effect of boldine on the
progression of kidney disease using the 2K1C hypertension model and identifying
mediators in the RAS, such as TGF-β, that could be modulated by this
alkaloid. Toward this hypothesis, rats (n = 5/group) were treated with boldine
(50 mg/kg/day, gavage) for six weeks after 2K1C surgery (pressure ≥ 180 mmHg).
Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U
prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive
substances (TBARS). The evolution of systolic blood pressure (SBP) was followed
weekly. Alpha-smooth muscle actin (α-SMA) and Col III were used as markers
of kidney damage; ED-1 and osteopontin (OPN) were used as markers of
inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF
β. Boldine treatment reduced the UProt/UCrea ratio, plasma TBARS, and
slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control
animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED
1, and OPN were lower when compared to 2K1C rats. Boldine prevented the increase
in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney
damage. These results suggest that boldine could potentially be used as a
nutraceutic.
PMID- 29941814
TI - Targeting TGFbeta Signaling to Address Fibrosis Using Antisense Oligonucleotides.
AB - Fibrosis results from the excessive accumulation of extracellular matrix in
chronically injured tissue. The fibrotic process is governed by crosstalk between
many signaling pathways. The search for an effective treatment is further
complicated by the fact that there is a degree of tissue-specificity in the
pathways involved, although the process is not completely understood for all
tissues. A plethora of drugs have shown promise in pre-clinical models, which is
not always borne out translationally in clinical trial. With the recent approvals
of two antisense oligonucleotides for the treatment of the genetic diseases
Duchenne muscular dystrophy and spinal muscular atrophy, we explore here the
potential of antisense oligonucleotides to knockdown the expression of pro
fibrotic proteins. We give an overview of the generalized fibrotic process,
concentrating on key players and highlight where antisense oligonucleotides have
been used effectively in cellular and animal models of different fibrotic
conditions. Consideration is given to the advantages antisense oligonucleotides
would have as an anti-fibrotic therapy alongside factors that would need to be
addressed to improve efficacy. A prospective outlook for the development of
antisense oligonucleotides to target fibrosis is outlined.
PMID- 29941817
TI - The Association between Age, Comorbidities and Use of Radiotherapy in Women with
Breast Cancer: Implications for Survival.
AB - Background: Radiotherapy (RT) plays an important role in the management and
survival of patients with breast cancer. The aim of this study was to examine the
association between age, comorbidities and use of RT in this population. Methods:
Patients diagnosed with breast cancer from 2004-2013 were identified from the
American College of Surgeons National Cancer Database (NCDB). Follow-up time was
measured from the date of diagnosis (baseline) to the date of death or censoring.
Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were used as
the measure of association. Results: Independently of comorbidities and other
important outcome-related factors, patients >65 years of age who received RT
survived significantly longer than those who did not receive RT (aHR = 0.53, 95%
CI = 0.52-0.54). However, as women aged, those with comorbidities were less
likely to receive RT (adjusted p-trend by age < 0.0001). Conclusions: The
development of decision-making tools to assist clinicians, and older women with
breast cancer and comorbidities, are needed to facilitate personalized treatment
plans regarding RT. This is particularly relevant as the population ages and the
number of women with breast cancer is expected to increase in the near future.
PMID- 29941819
TI - Discovery of the Potential Biomarkers for Discrimination between Hedyotis diffusa
and Hedyotis corymbosa by UPLC-QTOF/MS Metabolome Analysis.
AB - Hedyotis diffuse Willd. (HD) and Hedyotis corymbosa (L.) Lam. (HC), two closely
related species of the same genus, are both used for health benefits and disease
prevention in China. HC is also indiscriminately sold as HD in the wholesale
chain and food markets. This confusion has led to a growing concern about their
identification and quality evaluation. In order to further understand the
molecular diversification between them, we focus on the screening of chemical
components and the analysis of non-targeted metabolites. In this study, UPLC-QTOF
MSE, UNIFI platform and multivariate statistical analyses were used to profile
them. Firstly, a total of 113 compounds, including 80 shared chemical
constituents of the two plants, were identified from HC and HD by using the UNIFI
platform. Secondly, the differences between two herbs were highlighted with the
comparative analysis. As a result, a total of 33 robust biomarkers enabling the
differentiation were discovered by using multivariate statistical analyses. For
HC, there were 18 potential biomarkers (either the contents were much greater
than in HD or being detected only in HC) including three iridoids, eight
flavonoids, two tannins, two ketones, one alcohol and two monoterpenes. For HD,
there were15 potential biomarkers (either the contents were much greater than in
HC or being detected only in HD) including two iridoids, eight flavonoids, one
tannin, one ketone, and three anthraquinones. With a comprehensive consideration
of the contents or the MS responses of the chemical composition, Hedycoryside A
and B, detected only in HC, could be used for rapid identification of HC. The
compounds 1,3-dihydroxy-2-methylanthraquinone and 2-hydroxy-3
methylanthraquinone, detected only in HD, could be used for rapid identification
of that plant. The systematic comparison of similarities and differences between
two confusing Chinese herbs will provide reliable characterization profiles to
clarify the pharmacological fundamental substances. HC should not be used as the
substitute of HD.
PMID- 29941816
TI - Do Actomyosin Single-Molecule Mechanics Data Predict Mechanics of Contracting
Muscle?
AB - In muscle, but not in single-molecule mechanics studies, actin, myosin and
accessory proteins are incorporated into a highly ordered myofilament lattice. In
view of this difference we compare results from single-molecule studies and
muscle mechanics and analyze to what degree data from the two types of studies
agree with each other. There is reasonable correspondence in estimates of the
cross-bridge power-stroke distance (7-13 nm), cross-bridge stiffness (~2 pN/nm)
and average isometric force per cross-bridge (6-9 pN). Furthermore, models
defined on the basis of single-molecule mechanics and solution biochemistry give
good fits to experimental data from muscle. This suggests that the ordered
myofilament lattice, accessory proteins and emergent effects of the sarcomere
organization have only minor modulatory roles. However, such factors may be of
greater importance under e.g., disease conditions. We also identify areas where
single-molecule and muscle data are conflicting: (1) whether force generation is
an Eyring or Kramers process with just one major power-stroke or several sub
strokes; (2) whether the myofilaments and the cross-bridges have Hookean or non
linear elasticity; (3) if individual myosin heads slip between actin sites under
certain conditions, e.g., in lengthening; or (4) if the two heads of myosin
cooperate.
PMID- 29941820
TI - Spray-Drying of Electrode Materials for Lithium- and Sodium-Ion Batteries.
AB - The performance of electrode materials in lithium-ion (Li-ion), sodium-ion (Na
ion) and related batteries depends not only on their chemical composition but
also on their microstructure. The choice of a synthesis method is therefore of
paramount importance. Amongst the wide variety of synthesis or shaping routes
reported for an ever-increasing panel of compositions, spray-drying stands out as
a versatile tool offering demonstrated potential for up-scaling to industrial
quantities. In this review, we provide an overview of the rapidly increasing
literature including both spray-drying of solutions and spray-drying of
suspensions. We focus, in particular, on the chemical aspects of the formulation
of the solution/suspension to be spray-dried. We also consider the post
processing of the spray-dried precursors and the resulting morphologies of
granules. The review references more than 300 publications in tables where
entries are listed based on final compound composition, starting materials,
sources of carbon etc.
PMID- 29941821
TI - Microscopic Electron Dynamics in Metal Nanoparticles for Photovoltaic Systems.
AB - Nanoparticles—regularly patterned or randomly dispersed—are a key
ingredient for emerging technologies in photonics. Of particular interest are
scattering and field enhancement effects of metal nanoparticles for energy
harvesting and converting systems. An often neglected aspect in the modeling of
nanoparticles are light interaction effects at the ultimate nanoscale beyond
classical electrodynamics. Those arise from microscopic electron dynamics in
confined systems, the accelerated motion in the plasmon oscillation and the
quantum nature of the free electron gas in metals, such as Coulomb repulsion and
electron diffusion. We give a detailed account on free electron phenomena in
metal nanoparticles and discuss analytic expressions stemming from microscopic
(Random Phase Approximation—RPA) and semi-classical (hydrodynamic)
theories. These can be incorporated into standard computational schemes to
produce more reliable results on the optical properties of metal nanoparticles.
We combine these solutions into a single framework and study systematically their
joint impact on isolated Au, Ag, and Al nanoparticles as well as dimer
structures. The spectral position of the plasmon resonance and its broadening as
well as local field enhancement show an intriguing dependence on the particle
size due to the relevance of additional damping channels.
PMID- 29941822
TI - Mechanism and Characteristics of Humidity Sensing with Polyvinyl Alcohol-Coated
Fiber Surface Plasmon Resonance Sensor.
AB - A surface plasmon resonance (SPR) sensor based on a side-polished single mode
fiber coated with polyvinyl alcohol (PVA) is demonstrated for relative humidity
(RH) sensing. The SPR sensor exhibits a resonant dip in the transmission spectrum
in ambient air after PVA film coating, and the resonant wavelength shifts to
longer wavelengths as the thickness of the PVA film increases. When RH changes,
the resonant dip of the sensor with different film-thicknesses exhibits
interesting characteristics for optical spectrum evolution. For sensors with
initial wavelengths between 550 nm and 750 nm, the resonant dip shifts to longer
wavelengths with increasing RH. The averaged sensitivity increases firstly and
then drops, and shows a maximal sensitivity of 1.01 nm/RH%. Once the initial
wavelength of the SPR sensor exceeds 850 nm, an inflection point of the resonant
wavelength shift can be observed with RH increasing, and the resonant dip shifts
to shorter wavelengths for RH values exceeding this point, and sensitivity as
high as −4.97 nm/RH% can be obtained in the experiment. The sensor is
expected to have potential applications in highly sensitive and cost effective
humidity sensing.
PMID- 29941823
TI - Mechanical Performance of Multidirectional Buckling-Based Negative Stiffness
Metamaterials: An Analytical and Numerical Study.
AB - Unidirectional, bidirectional and tridirectional Buckling-based Negative
Stiffness (BNS) lattice metamaterials are designed by adding prefabricated curved
beams into multidimensional rigid frames. Finite Element Analysis models are
built, and their mechanical performance is investigated and discussed. First,
geometric parameters of the curved beam were systematically studied with
numerical analyses and the results were validated by theoretical solutions. Next,
within unidirectional designs of different layer numbers, the basic properties of
multilayer BNS metamaterials were revealed via quasi-static compressions. Then,
the bidirectional and tridirectional designs were loaded on orthogonal axes to
research both the quasi-static and dynamic behaviors. For dynamic analysis
conditions, simulation scenarios of different impact velocities were implemented
and compared. The results demonstrate that the proposed numerical analysis step
has accurately predicted the force-displacement relations of both the curved beam
and multilayer designs and the relations can be tuned via different geometric
parameters. Moreover, the macroscopic performance of the metamaterials is
sensitive to the rigidity of supporting frames. The shock force during impact is
reduced down below the buckling thresholds of metamaterial designs and sharp
impact damage is avoided. The presented metamaterials are able to undergo
multiaxial stress conditions while retaining the negative stiffness effect and
energy-absorbing nature and possess abundant freedom of parametric design, which
is potentially useful in shock and vibration engineering.
PMID- 29941818
TI - Ibero-American Consensus on Low- and No-Calorie Sweeteners: Safety, Nutritional
Aspects and Benefits in Food and Beverages.
AB - International scientific experts in food, nutrition, dietetics, endocrinology,
physical activity, paediatrics, nursing, toxicology and public health met in
Lisbon on 2-4 July 2017 to develop a Consensus on the use of low- and no-calorie
sweeteners (LNCS) as substitutes for sugars and other caloric sweeteners. LNCS
are food additives that are broadly used as sugar substitutes to sweeten foods
and beverages with the addition of fewer or no calories. They are also used in
medicines, health-care products, such as toothpaste, and food supplements. The
goal of this Consensus was to provide a useful, evidence-based, point of
reference to assist in efforts to reduce free sugars consumption in line with
current international public health recommendations. Participating experts in the
Lisbon Consensus analysed and evaluated the evidence in relation to the role of
LNCS in food safety, their regulation and the nutritional and dietary aspects of
their use in foods and beverages. The conclusions of this Consensus were: (1)
LNCS are some of the most extensively evaluated dietary constituents, and their
safety has been reviewed and confirmed by regulatory bodies globally including
the World Health Organisation, the US Food and Drug Administration and the
European Food Safety Authority; (2) Consumer education, which is based on the
most robust scientific evidence and regulatory processes, on the use of products
containing LNCS should be strengthened in a comprehensive and objective way; (3)
The use of LNCS in weight reduction programmes that involve replacing caloric
sweeteners with LNCS in the context of structured diet plans may favour
sustainable weight reduction. Furthermore, their use in diabetes management
programmes may contribute to a better glycaemic control in patients, albeit with
modest results. LNCS also provide dental health benefits when used in place of
free sugars; (4) It is proposed that foods and beverages with LNCS could be
included in dietary guidelines as alternative options to products sweetened with
free sugars; (5) Continued education of health professionals is required, since
they are a key source of information on issues related to food and health for
both the general population and patients. With this in mind, the publication of
position statements and consensus documents in the academic literature are
extremely desirable.
PMID- 29941824
TI - Estimated Burden of Serious Fungal Diseases in Serbia.
AB - For the first time, we aimed to estimate the burden of serious fungal infections
or diseases (SFD) and highlight national epidemiological features in Serbia. Data
on population and underlining conditions were extracted from the Statistical
Office of the Republic of Serbia, World Bank, the Institute of Public Health of
Serbia, the World Health Organization, National reference laboratory for medical
mycology, the national registries of Serbian professional societies, and relevant
publications. The population structure/inhabitants in 2016 (not including the
autonomous region Kosovo & Metohija) was 7,058,322; with 6,041,743 adults
(85.6%). The populations at risk (total cases per year) were: HIV infected 2441;
acute myeloid leukemia 212; stem cell transplantation 151; solid organ
transplants 59; chronic obstructive pulmonary disease 250,302; adult asthmatics
311,806; adult cystic fibrosis 65; pulmonary tuberculosis 898; lung cancer 7260;
intensive care unit admissions 19,821; and renal support 520. Annual fungal
disease cases estimated are: candidemia 518; invasive aspergillosis 619; Candida
peritonitis 187; Pneumocystis jirovecii pneumonia 62; cryptococcosis 5;
mucormycosis or fusariosis 23; severe asthma with fungal sensitization 10,393;
allergic bronchopulmonary aspergillosis 9094; chronic pulmonary aspergillosis
448, recurrent Candida vaginitis 135,303; oral candidiasis 208,489; esophageal
candidiasis 173, fungal keratitis 70; tinea capitis 300; and onychomycosis
342,721. We expect that 156,825 people suffer from serious SFD each year
(2221/100,000), and 409 dies annually. Additionally, the prevalence of
superficial infections exceeds 1,008,995 cases (14,295/100,000). The first
Rhinosporidium outbreak in Europe was associated with Serbian Silver Lake. The
plant pathogen Fusarium seems to be emerging in Serbian pediatric haematooncology
settings. Candida auris and endemic mycoses have not been observed to date. These
general estimates provide a primer for further efforts to study fungal
epidemiology in Serbia.
PMID- 29941825
TI - Six Degrees of Freedom Displacement Measurement System for Wafer Stage Composed
of Hall Sensors.
AB - This paper proposes a decoupled six degrees of freedom (DOF) displacement
measurement methodology, which is accomplished by utilizing six pairs of
permanent magnets and six Hall sensors. Firstly, the coordinate transformation
was mathematically derived, which represented the relationships between the main
coordinate system of the motion system and each body coordinate system of the
Hall sensors. With the aid of an ellipsoid function and the least squares method,
only the output voltages of the six Hall sensors were required to decouple the
six-DOF displacement and inclination of the motion platform with high accuracy.
Finally, the experimental measurements demonstrate the effectiveness of the six
DOF displacement measurement methodology, based on which the maximum errors of
displacements can reach 0.23 mm and the maximum errors of inclinations can reach
0.07°.
PMID- 29941826
TI - A Network Equivalent-Based Algorithm for Adaptive Parameter Tuning in 802.15.4
WSNs.
AB - Previous studies have shown that in many wireless sensor network applications the
IEEE 802.15.4 carrier sense multiple access with collision avoidance (CSMA/CA)
mechanism with default parameters cannot guarantee the constraints of
reliability, time efficiency, or energy efficiency. Although many adaptive
parameter tuning algorithms have been proposed, many of them cannot correctly
identify the changes of the network condition and are unable to effectively
perform the parameter tuning operation. Considering the randomness that CSMA/CA
brings about, for most of the proposed algorithms, it is a challenge to
distinguish significant violations that were caused by actual changes of the
network from the general fluctuations that were due to CSMA/CA. In this paper, we
propose a lightweight algorithm called the network equivalent adaptive parameter
tuning (NEAPT) algorithm. It is fully distributed and can work without any
predefined information or acknowledgement. NEAPT not only takes reliability as an
evaluation of a network condition, but it proposes a synthetic value, called the
equivalent node number, and takes it as another reference for a network
condition. Simulation results show that by taking both reliability and the
equivalent node number into consideration, NEAPT can effectively identify the
network changes and provide adequate and steady performances for wireless sensor
networks (WSNs) in both stationary and dynamic conditions.
PMID- 29941827
TI - Chemical Composition and In Vitro Antimicrobial Efficacy of Sixteen Essential
Oils against Escherichia coli and Aspergillus fumigatus Isolated from Poultry.
AB - Escherichia coli and Aspergillus fumigatus are two pathogens largely present
among poultry. They can cause mild or severe forms of disease, and are associated
with significant economic losses. The aim of the present study was to investigate
the chemical composition and the in vitro antimicrobial activity of sixteen
essential oils (EOs) and five mixtures against E. coli and A. fumigatus strains
previously isolated from poultry. The study was performed with the following EOs:
Aloysiatryphilla, Boswelliasacra, Cinnamomum zeylanicum, Citrus aurantium, Citrus
bergamia, Citrus limon, Citrus reticulata, Cymbopogon citratus, Eucalyptus
globulus, Lavandula hybrida, Litsea cubeba, Ocimum basilicum, Melaleuca
alternifolia, Mentha piperita, Pelargoniumgraveolens, and Syzygium aromaticum.
Moreover, the following mixtures were also tested: L. cubeba and C. citratus
(M1), L. cubeba and A. triphylla (M2), A. triphylla and C. citratus (M3), A.
triphylla, C.citratus and L. cubeba (M4), S. aromaticum and C. zeylanicum (M5).
One hundred and ninety-one compounds were identified in the tested EOs and
mixtures. MIC determination found good anti-E. coli activity with C. zeylanicum
(2.52 mg/mL), C. citratus (1.118 mg/mL), L. cubeba (1.106 mg/mL), M. piperita
(1.14 mg/mL) and S. aromaticum (1.318 mg/mL) EOs. Among the mixtures, M5 showed
the best result with a MIC value of 2.578 mg/mL. The best antimycotic activity
was showed by A. triphylla (0.855 mg/mL), followed by C. citratus (0.895 mg/mL),
while C. aurantium, M. piperita, B. sacra and P. graveolens did not yield any
antifungal effect at the highest dilution. The mixtures exhibited no antifungal
activity at all. This study shows promising results in order to use EOs in the
environment for disinfection purposes in poultry farms and/or in hatcheries.
PMID- 29941828
TI - Interface Passivation Effects on the Photovoltaic Performance of Quantum Dot
Sensitized Inverse Opal TiO2 Solar Cells.
AB - Quantum dot (QD)-sensitized solar cells (QDSSCs) are expected to achieve higher
energy conversion efficiency than traditional single-junction silicon solar cells
due to the unique properties of QDs. An inverse opal (IO)-TiO2 (IO-TiO2)
electrode is useful for QDSSCs because of its three-dimensional (3D) periodic
nanostructures and better electrolyte penetration compared to the normal
nanoparticles (NPs)-TiO2 (NPs-TiO2) electrode. We find that the open-circuit
voltages Voc of the QDSSCs with IO-TiO2 electrodes are higher than those of
QDSSCs with NPs-TiO2 electrodes. One important strategy for enhancing
photovoltaic conversion efficiency of QDSSCs with IO-TiO2 electrodes is surface
passivation of photoanodes using wide-bandgap semiconducting materials. In this
study, we have proposed surface passivation on IO-TiO2 with ZnS coating before QD
deposition. The efficiency of QDSSCs with IO-TiO2 electrodes is largely improved
(from 0.74% to 1.33%) because of the enhancements of Voc (from 0.65 V to 0.74 V)
and fill factor (FF) (from 0.37 to 0.63). This result indicates that ZnS
passivation can reduce the interfacial recombination at the IO-TiO2/QDs and IO
TiO2/electrolyte interfaces, for which two possible explanations can be
considered. One is the decrease of recombination at IO-TiO2/electrolyte
interfaces, and the other one is the reduction of the back-electron injection
from the TiO2 electrode to QDs. All of the above results are effective for
improving the photovoltaic properties of QDSSCs.
PMID- 29941829
TI - Double Feedback Control Method for Determining Early-Age Restrained Creep of
Concrete Using a Temperature Stress Testing Machine.
AB - Early-age restrained creep influences the cracking properties of concrete.
However, conventional creep measurements require a large number of tests to
predict the restrained creep as it is influenced by the combined effects of
variable temperature, creep recovery, and varying compression and tension
stresses. In this work, a double feedback control method for temperature stress
testing was developed to measure the early-age restrained creep of concrete. The
results demonstrate that the conventional single feedback control method neglects
the effect of restrained elastic deformation, thus providing a larger-than-actual
creep measurement. The tests found that the double feedback control method
eliminates the influence of restrained elastic deformation. The creep results
from the double feedback method match well with results from the single feedback
method after compensation for the effects of restrained elastic deformation is
accounted for. The difference in restrained creep between the single and double
feedback methods is significant for concrete with a low modulus of elasticity but
can be neglected in concrete with a high modulus of elasticity. The ratio between
creep and free deformation was found to be 40-60% for low, moderate, and high
strength concretes alike. The double feedback control method is therefore
recommended for determining the restrained creep using a temperature stress
testing machine.
PMID- 29941831
TI - Ubidecarenone-Loaded Nanostructured Lipid Carrier (UB-NLC): Percutaneous
Penetration and Protective Effects Against Hydrogen Peroxide-Induced Oxidative
Stress on HaCaT Cells.
AB - The objective of the investigation was to evaluate the percutaneous penetration
of a ubidecarenone-loaded nanostructured lipid carrier (UB-NLC) and to illuminate
the protective effects of UB-NLC for amelioration of hydrogen peroxide-induced
oxidative damage on HaCaT cells. Ubidecarenone (UB) was encapsulated in a
nanostructured lipid carrier (NLC), which was manufactured by homogenization. The
morphological and dimensional properties of the prepared UB-NLC were studied by
freeze-fracture transmission electron microscopy (FF-TEM) and photon correlation
spectroscopy (PCS). Percutaneous penetration of UB-NLC was carried out by the
Franz diffusion cells method. The change of cellular morphology was identified
through a non-invasive time-lapse imaging system. The assessment was achieved via
the evaluation of the levels of oxidative stress markers: reactive oxygen species
(ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and
malondialdehyde (MDA). Percutaneous penetration of UB loaded in NLC formulation
was enhanced in comparison to free UB. Preincubation of HaCaT cells with UB-NLC
attenuated the level of intracellular generation of ROS. Lipid peroxidation was
diminished by UB-NLC via inhibition of MDA formation. Pretreatment of cells with
UB-NLC reestablished the activity of cellular antioxidant enzymes (SOD and GSH
PX). On the basis of the investigation conducted, results suggest that
formulating UB as NLC is advantageous for topical delivery and treatment of
oxidative stress-induced human diseases.
PMID- 29941830
TI - Structure-Activity Relationship of Cannabis Derived Compounds for the Treatment
of Neuronal Activity-Related Diseases.
AB - Cannabis sativa active compounds are extensively studied for their therapeutic
effects, beyond the well-known psychotropic activity. C. Sativa is used to treat
different medical indications, such as multiple sclerosis, spasticity, epilepsy,
ulcerative colitis and pain. Simultaneously, basic research is discovering new
constituents of cannabis-derived compounds and their receptors capable of
neuroprotection and neuronal activity modulation. The function of the various
phytochemicals in different therapeutic processes is not fully understood, but
their significant role is starting to emerge and be appreciated. In this review,
we will consider the structure-activity relationship (SAR) of cannabinoid
compounds able to bind to cannabinoid receptors and act as therapeutic agents in
neuronal diseases, e.g., Parkinson’s disease.
PMID- 29941832
TI - Physicochemical and Microbiological Assessment of an Experimental Composite Doped
with Triclosan-Loaded Halloysite Nanotubes.
AB - This study is aimed at evaluating the effects of triclosan-encapsulated
halloysite nanotubes (HNT/TCN) on the physicochemical and microbiological
properties of an experimental dental composite. A resin composite doped with
HNT/TCN (8% w/w), a control resin composite without nanotubes (HNT/TCN-0%) and a
commercial nanofilled resin (CN) were assessed for degree of conversion (DC),
flexural strength (FS), flexural modulus (FM), polymerization stress (PS),
dynamic thermomechanical (DMA) and thermogravimetric analysis (TGA). The
antibacterial properties (M) were also evaluated using a 5-day biofilm assay
(CFU/mL). Data was submitted to one-way ANOVA and Tukey tests. There was no
significant statistical difference in DC, FM and RU between the tested composites
(p > 0.05). The FS and CN values attained with the HNT/TCN composite were higher
(p < 0.05) than those obtained with the HNT/TCN-0%. The DMA analysis showed
significant differences in the TAN δ (p = 0.006) and Tg (p = 0) between the
groups. TGA curves showed significant differences between the groups in terms of
degradation (p = 0.046) and weight loss (p = 0.317). The addition of HNT/TCN
induced higher PS, although no significant antimicrobial effect was observed (p =
0.977) between the groups for CFUs and (p = 0.557) dry weight. The incorporation
of HNT/TCN showed improvements in physicochemical and mechanical properties of
resin composites. Such material may represent an alternative choice for
therapeutic restorative treatments, although no significance was found in terms
of antibacterial properties. However, it is possible that current antibacterial
tests, as the one used in this laboratory study, may not be totally appropriate
for the evaluation of resin composites, unless accompanied with aging protocols
(e.g., thermocycling and load cycling) that allow the release of therapeutic
agents incorporated in such materials.
PMID- 29941833
TI - Mental Well-Being of Older People in Finland during the First Year in Senior
Housing and Its Association with Physical Performance.
AB - Growing numbers of older people relocate to senior housing, when their physical
or mental performance declines. The relocation is known to be one of the most
stressful events in the life of older people and affect their mental and physical
well-being. More information about the relationships between mental and physical
parameters is required. We examined self-reported mental well-being of 81 older
people (aged 59-93, living in northern Finland), and changes in it 3 and 12
months after relocation to senior housing. The first measurement was 3 months and
the second measurement 12 months after relocation. Most participants were female
(70%). Their physical performance was also measured, and associations between
these two were analyzed. After 12 months, mental capability was very good or
quite good in 38% of participants, however 22% of participants felt depressive
symptoms daily or weekly. Moreover, 39% of participants reported daily or weekly
loneliness. After 12 months participants reported a significant increase in
forgetting appointments, losing items and difficulties in learn new things. They
felt that opportunities to make decisions concerning their own life significantly
decreased. Furthermore, their instrumental activities of daily living (IADL),
dominant hand’s grip strength and walking speed decreased significantly.
Opportunities to make decisions concerning their life, feeling safe, loneliness,
sleeping problems, negative thoughts as well as fear of falling or having an
accident outdoors were associated with these physical parameters. In addition to
assessing physical performance and regular exercise, the various components of
mental well-being and their interactions with physical performance should be
considered during adjustment to senior housing.
PMID- 29941834
TI - Automated Cell Treatment for Competence and Transformation of Escherichia coli in
a High-Throughput Quasi-Turbidostat Using Microtiter Plates.
AB - Metabolic engineering and genome editing strategies often lead to large strain
libraries of a bacterial host. Nevertheless, the generation of competent cells is
the basis for transformation and subsequent screening of these strains. While
preparation of competent cells is a standard procedure in flask cultivations,
parallelization becomes a challenging task when working with larger libraries and
liquid handling stations as transformation efficiency depends on a distinct
physiological state of the cells. We present a robust method for the preparation
of competent cells and their transformation. The strength of the method is that
all cells on the plate can be maintained at a high growth rate until all cultures
have reached a defined cell density regardless of growth rate and lag phase
variabilities. This allows sufficient transformation in automated high throughput
facilities and solves important scheduling issues in wet-lab library screenings.
We address the problem of different growth rates, lag phases, and initial cell
densities inspired by the characteristics of continuous cultures. The method
functions on a fully automated liquid handling platform including all steps from
the inoculation of the liquid cultures to plating and incubation on agar plates.
The key advantage of the developed method is that it enables cell harvest in 96
well plates at a predefined time by keeping fast growing cells in the exponential
phase as in turbidostat cultivations. This is done by a periodic monitoring of
cell growth and a controlled dilution specific for each well. With the described
methodology, we were able to transform different strains in parallel. The
transformants produced can be picked and used in further automated screening
experiments. This method offers the possibility to transform any combination of
strain- and plasmid library in an automated high-throughput system, overcoming an
important bottleneck in the high-throughput screening and the overall chain of
bioprocess development.
PMID- 29941835
TI - Complexity of Daily Physical Activity Is More Sensitive Than Conventional Metrics
to Assess Functional Change in Younger Older Adults.
AB - The emerging mHealth applications, incorporating wearable sensors, enables
continuous monitoring of physical activity (PA). This study aimed at analyzing
the relevance of a multivariate complexity metric in assessment of functional
change in younger older adults. Thirty individuals (60-70 years old) participated
in a 4-week home-based exercise intervention. The Community Balance and Mobility
Scale (CBMS) was used for clinical assessment of the participants’
functional balance and mobility performance pre- and post- intervention.
Accelerometers worn on the low back were used to register PA of one week before
and in the third week of the intervention. Changes in conventional univariate PA
metrics (percentage of walking and sedentary time, step counts, mean cadence) and
complexity were compared to the change as measured by the CBMS. Statistical
analyses (21 participants) showed significant rank correlation between the change
as measured by complexity and CBMS (ρ = 0.47, p = 0.03). Smoothing the
activity output improved the correlation (ρ = 0.58, p = 0.01). In contrast,
change in univariate PA metrics did not show correlations. These findings
demonstrate the high potential of the complexity metric being useful and more
sensitive than conventional PA metrics for assessing functional changes in
younger older adults.
PMID- 29941836
TI - Healing of Ischemic Colon Anastomosis in Rats Could Be Provided by Administering
Dexpanthenol or Coenzyme Q10.
AB - BACKGROUND: In this study, the effectiveness of dexpanthenol and coenzyme Q10
(CoQ10) on the healing of ischemic colon anastomosis was investigated. METHODS:
Forty eight male Wistar Albino rats were divided into four equal groups (Sham-S,
Sham-I, DXP, Q10). Following full layer colon resection, single layer colon
anastomosis, without creating ischemia, was performed on the Sham-S group. The
same experimental model was performed on remaining groups after ischemia was
created. Intraperitoneal dexpanthenol and CoQ10 was administered to the DXP and
Q10 groups once a day for three days. Ten days later, all colon anastomoses were
investigated histopathologically and biochemically, as well as their burst
pressure values, in all sacrificed rats. RESULTS: The highest burst pressure
value was observed in the Sham-S group, decreasing from high to low in the DXP,
Q10, and Sham-I groups, respectively (p = 0.008). Furthermore, tissue
hydroxyproline (p = 0.001) level values were significantly different among the
groups. Additionally, histopathological analysis revealed a significant
difference among groups regarding reepithelization (p = 0.027) and
polymorphonuclear leukocyte density (p = 0.022). CONCLUSIONS: This preliminary
study has shown that ischemia-reperfusion injury may impair the healing of colon
anastomosis and it has been concluded that dexpanthenol and CoQ10 may have
positive effects on the healing of ischemic colon anastomosis in rat, although re
epithelization may be adversely affected using CoQ10.
PMID- 29941837
TI - A Novel Acquired t(2;4)(q36.1;q24) with a Concurrent Submicroscopic
del(4)(q23q24) in An Adult with Polycythemia Vera.
AB - Background: Polycythemia vera (PV) is a clonal myeloid stem cell disease
characterized by a growth-factor independent erythroid proliferation with an
inherent tendency to transform into overt acute myeloid malignancy. Approximately
95% of the PV patients harbor the JAK2V617F mutation while less than 35% of the
patients harbor cytogenetic abnormalities at the time of diagnosis. Methods and
Results: Here we present a JAK2V617F positive PV patient where G-banding revealed
an apparently balanced t(2;4)(q35;q21), which was confirmed by 24-color
karyotyping. Oligonucleotide array-based Comparative Genomic Hybridization (aCGH)
analysis revealed an interstitial 5.4 Mb large deletion at 4q23q24. Locus
specific fluorescent in situ hybridization (FISH) analyses confirmed the mono
allelic 4q deletion and that it was located on der(4)t(2;4). Additional locus
specific bacterial artificial chromosome (BAC) probes and mBanding refined the
breakpoint on chromosome 2. With these methods the karyotype was revised to
46,XX,t(2;4)(q36.1;q24)[18]/46,XX[7]. Conclusions: This is the first report on a
PV patient associated with an acquired novel t(2;4)(q36.1;q24) and a concurrent
submicroscopic deletion del(4)(q23q24). The study also underscores the benefit of
combined usage of FISH and oligo-based aCGH analysis in characterizing
chromosomal abnormalities. The present findings provide additional clues to
unravel important molecular pathways in PV to obtain the full spectrum of
acquired chromosomal and genomic aberrations, which eventually may improve
treatment options.
PMID- 29941839
TI - Toxic Effects of Methanol among Illegally Dispatched Workers at Aluminum CNC
Cutting Process in Small-Scale, Third-Tier Subcontractor Factories of Smartphone
Manufacturers in the Republic of Korea.
AB - An outbreak of occupational methanol poisoning occurred in small-scale, third
tier factories of large-scale smartphone manufacturers in the Republic of Korea
in 2016. To investigate the working environment and the health effects of
methanol exposure among co-workers in the methanol poisoning cases, we performed
a cross-sectional study on 155 workers at five aluminum Computerized Numerical
Control (CNC) cutting factories. Gas chromatography measured air and urinary
methanol concentration. In the medical examination, symptom surveys,
ophthalmological examinations, and neurobehavioral tests were done. Multiple
logistic regression analyses controlling for age and sex were conducted to reveal
the association of employment duration with symptoms. Air concentrations of
methanol in factory A and E ranged from 228.5 to 2220.0 ppm. Mean urinary
methanol concentrations of the workers in each factory were from 3.5 mg/L up to
91.2 mg/L. The odds ratios for symptoms of deteriorating vision and central
nervous system (CNS) increased according to the employment duration after
adjusting for age and sex. Four cases with an injured optic nerve and two cases
with decreased neurobehavioral function were founded among co-workers of the
victims. This study showed that the methanol exposure under poor environmental
control not only produces eye and CNS symptoms but also affects neurobehavioral
function and the optic nerve. The role of subcontracting production and
dispatched work under poor environmental control was discussed.
PMID- 29941838
TI - Endophytic Fungi: A Source of Potential Antifungal Compounds.
AB - The emerging and reemerging forms of fungal infections encountered in the course
of allogeneic bone marrow transplantations, cancer therapy, and organ transplants
have necessitated the discovery of antifungal compounds with enhanced efficacy
and better compatibility. A very limited number of antifungal compounds are in
practice against the various forms of topical and systemic fungal infections. The
trends of new antifungals being introduced into the market have remained
insignificant while resistance towards the introduced drug has apparently
increased, specifically in patients undergoing long-term treatment. Considering
the immense potential of natural microbial products for the isolation and
screening of novel antibiotics for different pharmaceutical applications as an
alternative source has remained largely unexplored. Endophytes are one such
microbial community that resides inside all plants without showing any symptoms
with the promise of producing diverse bioactive molecules and novel metabolites
which have application in medicine, agriculture, and industrial set ups. This
review substantially covers the antifungal compounds, including volatile organic
compounds, isolated from fungal endophytes of medicinal plants during 2013-2018.
Some of the methods for the activation of silent biosynthetic genes are also
covered. As such, the compounds described here possess diverse configurations
which can be a step towards the development of new antifungal agents directly or
precursor molecules after the required modification.
PMID- 29941840
TI - Improved Visualization of Hydroacoustic Plumes Using the Split-Beam Aperture
Coherence.
AB - Natural seepage of methane into the oceans is considerable, and plays a role in
the global carbon cycle. Estimating the amount of this greenhouse gas entering
the water column is important in order to understand their environmental impact.
In addition, leakage from man-made structures such as gas pipelines may have
environmental and economical consequences and should be promptly detected. Split
beam echo sounders (SBES) detect hydroacoustic plumes due to the significant
contrast in acoustic impedance between water and free gas. SBES are also powerful
tools for plume characterization, with the ability to provide absolute acoustic
measurements, estimate bubble trajectories, and capture the frequency dependent
response of bubbles. However, under challenging conditions such as deep water and
considerable background noise, it can be difficult to detect the presence of gas
seepage from the acoustic imagery alone. The spatial coherence of the wavefield
measured across the split beam sectors, quantified by the coherence factor (CF),
is a computationally simple, easily available quantity which complements the
acoustic imagery and may ease the ability to automatically or visually detect
bubbles in the water column. We demonstrate the benefits of CF processing using
SBES data from the Hudson Canyon, acquired using the Simrad EK80 SBES. We observe
that hydroacoustic plumes appear more clearly defined and are easier to detect in
the CF imagery than in the acoustic backscatter images.
PMID- 29941842
TI - A Robust Step Detection Algorithm and Walking Distance Estimation Based on Daily
Wrist Activity Recognition Using a Smart Band.
AB - Human activity recognition and pedestrian dead reckoning are an interesting field
because of their importance utilities in daily life healthcare. Currently, these
fields are facing many challenges, one of which is the lack of a robust algorithm
with high performance. This paper proposes a new method to implement a robust
step detection and adaptive distance estimation algorithm based on the
classification of five daily wrist activities during walking at various speeds
using a smart band. The key idea is that the non-parametric adaptive distance
estimator is performed after two activity classifiers and a robust step detector.
In this study, two classifiers perform two phases of recognizing five wrist
activities during walking. Then, a robust step detection algorithm, which is
integrated with an adaptive threshold, peak and valley correction algorithm, is
applied to the classified activities to detect the walking steps. In addition,
the misclassification activities are fed back to the previous layer. Finally,
three adaptive distance estimators, which are based on a non-parametric model of
the average walking speed, calculate the length of each strike. The experimental
results show that the average classification accuracy is about 99%, and the
accuracy of the step detection is 98.7%. The error of the estimated distance is
2.2-4.2% depending on the type of wrist activities.
PMID- 29941841
TI - Investigations of Structural Requirements for BRD4 Inhibitors through Ligand- and
Structure-Based 3D QSAR Approaches.
AB - The bromodomain containing protein 4 (BRD4) recognizes acetylated histone
proteins and plays numerous roles in the progression of a wide range of cancers,
due to which it is under intense investigation as a novel anti-cancer drug
target. In the present study, we performed three-dimensional quantitative
structure activity relationship (3D-QSAR) molecular modeling on a series of 60
inhibitors of BRD4 protein using ligand- and structure-based alignment and
different partial charges assignment methods by employing comparative molecular
field analysis (CoMFA) and comparative molecular similarity indices analysis
(CoMSIA) approaches. The developed models were validated using various
statistical methods, including non-cross validated correlation coefficient (r2),
leave-one-out (LOO) cross validated correlation coefficient (q2), bootstrapping,
and Fisher's randomization test. The highly reliable and predictive CoMFA (q2 =
0.569, r2 = 0.979) and CoMSIA (q2 = 0.500, r2 = 0.982) models were obtained from
a structure-based 3D-QSAR approach using Merck molecular force field (MMFF94).
The best models demonstrate that electrostatic and steric fields play an
important role in the biological activities of these compounds. Hence, based on
the contour maps information, new compounds were designed, and their binding
modes were elucidated in BRD4 protein's active site. Further, the activities and
physicochemical properties of the designed molecules were also predicted using
the best 3D-QSAR models. We believe that predicted models will help us to
understand the structural requirements of BRD4 protein inhibitors that belong to
quinolinone and quinazolinone classes for the designing of better active
compounds.
PMID- 29941843
TI - Correction: Oniciuc, E. A.; et al. The Present and Future of Whole Genome
Sequencing (WGS) and Whole Metagenome Sequencing (WMS) for Surveillance of
Antimicrobial Resistant Microorganisms and Antimicrobial Resistance Genes across
the Food Chain. Genes 2018, 9, 268.
AB - The authors wish to make the following changes to their paper [1]. Due to an
undetected mistake in the references management, certain errors appeared in the
reference list and a reference was duplicated in Table 1[...].
PMID- 29941844
TI - The Association between Mental Wellbeing, Levels of Harmful Drinking, and
Drinking Motivations: A Cross-Sectional Study of the UK Adult Population.
AB - Mental well-being and excessive alcohol consumption each represent a significant
public health concern, and evidence suggests an association between them.
Furthermore, drinking motivations associated with harmful drinking have been
studied, but not systematically in the UK population. A representative sample of
6174 UK adults aged 18-75 were surveyed online. Low risk drinkers were found to
have higher mental well-being than hazardous, harmful, and, probable, dependence
drinkers. Using a hierarchical multiple regression analysis, it was found that
just over 5% of the variance in well-being scores was accounted for by the level
of harmful drinking and drinking motivation; the most significant contribution
was drinking to cope. Among people drinking to cope, those drinking in more
harmful ways were statistically significantly more likely to have low well-being
compared to less harmful drinkers. In the UK adult population there is a clear
association between poor mental well-being and harmful drinking. Furthermore,
coping was a significant motivation to drink for many with low mental well-being.
While mental well-being was found to be directly linked with levels of harmful
drinking, the motivation for drinking was a stronger predictor of mental well
being.
PMID- 29941845
TI - Transfer Learning for Improved Audio-Based Human Activity Recognition.
AB - Human activities are accompanied by characteristic sound events, the processing
of which might provide valuable information for automated human activity
recognition. This paper presents a novel approach addressing the case where one
or more human activities are associated with limited audio data, resulting in a
potentially highly imbalanced dataset. Data augmentation is based on transfer
learning; more specifically, the proposed method: (a) identifies the classes
which are statistically close to the ones associated with limited data; (b)
learns a multiple input, multiple output transformation; and (c) transforms the
data of the closest classes so that it can be used for modeling the ones
associated with limited data. Furthermore, the proposed framework includes a
feature set extracted out of signal representations of diverse domains, i.e.,
temporal, spectral, and wavelet. Extensive experiments demonstrate the relevance
of the proposed data augmentation approach under a variety of generative
recognition schemes.
PMID- 29941846
TI - Nickel Sulfides Decorated SiC Foam for the Low Temperature Conversion of H2S into
Elemental Sulfur.
AB - The selective oxidation of H2S to elemental sulfur was carried out on a
NiS2/SiCfoam catalyst under reaction temperatures between 40 and 80 degrees C
using highly H2S enriched effluents (from 0.5 to 1 vol.%). The amphiphilic
properties of SiC foam provide an ideal support for the anchoring and growth of a
NiS2 active phase. The NiS2/SiC composite was employed for the desulfurization of
highly H2S-rich effluents under discontinuous mode with almost complete H2S
conversion (nearly 100% for 0.5 and 1 vol.% of H2S) and sulfur selectivity (from
99.6 to 96.0% at 40 and 80 degrees C, respectively), together with an
unprecedented sulfur-storage capacity. Solid sulfur was produced in large
aggregates at the outer catalyst surface and relatively high H2S conversion was
maintained until sulfur deposits reached 140 wt.% of the starting catalyst
weight. Notably, the spent NiS2/SiCfoam catalyst fully recovered its pristine
performance (H2S conversion, selectivity and sulfur-storage capacity) upon
regeneration at 320 degrees C under He, and thus, it is destined to become a
benchmark desulfurization system for operating in discontinuous mode.
PMID- 29941847
TI - DNA-Based Sensor for the Detection of an Organophosphorus Pesticide: Profenofos.
AB - In this work, we propose an electrochemical DNA aptasensor for the detection of
profenofos, an organophosphorus pesticide, based on a competitive format and
disposable graphite screen-printed electrodes (GSPEs). A thiol-tethered DNA
capture probe, which results to be complementary to the chosen aptamer sequence,
was immobilised on gold nanoparticles/polyaniline composite film-modified
electrodes (AuNPs/PANI/GSPE). Different profenofos solutions containing a fixed
amount of the biotinylated DNA aptamer were dropped onto the realized
aptasensors. The hybridisation reaction was measured using a streptavidin
alkaline phosphatase enzyme conjugate, which catalyses the hydrolysis of 1
naphthyl -phosphate. The 1-naphtol enzymatic product was detected by means of
differential pulse voltammetry (DPV). The aptasensor showed itself to work as a
signal off sensor, according to the competitive format used. A dose response
curve was obtained between 0.10 μM and 10 μM with a detection limit of 0.27
μM.
PMID- 29941848
TI - Association between Platescapes, Foodscapes, and Meal Energy Intake in Government
Employees from Muar, Johor, Malaysia.
AB - A microscale built environment was the focus in this cross-sectional study which
aimed to investigate the associations between platescapes, foodscapes, and meal
energy intake among subjects. A total of 133 subjects (54 male, 79 female) with
mean age 36.8 +/- 7.3 years completed a self-administered questionnaire on
sociodemographic characteristics, platescapes, and foodscape preferences. For
platescapes, a plate mapping method was used, where subjects were required to
place various sizes of food models on two different sized plates (23 cm and 28
cm) based on their preferences. For foodscape preferences, subjects were given a
23-cm plate and various food models differentiated by shapes and colours. Then,
24-h daily recalls (for one weekday and one weekend day) were obtained using
interviews. Significant differences were observed in meal energy intake (p <
0.05) between males (1741 +/- 339 kcal) and females (1625 +/- 247 kcal) and also
between age groups (p < 0.05). There was a significant difference (p < 0.0001) in
terms of subjects’ meal energy intake when comparing 23-cm plates (419 +/-
124 kcal) and 28-cm plates (561 +/- 143 kcal). The bigger plate (28 cm) (p <
0.01) was significantly associated with subjects’ meal energy intakes, but
this was not so for the 23-cm plate. There were significant differences in
subjects’ meal energy when comparing white rice and multicoloured rice (p <
0.0001), unicoloured and multicoloured proteins (p < 0.0001), and unicoloured and
multicoloured vegetables (p < 0.0001). There was a significant difference found
between round- and cube-shaped proteins (p < 0.05). The colours of rice (p <
0.01), protein (p < 0.05), and vegetables (p < 0.05) were significantly
associated with subjects’ meal energy. Only the shape of carrots in
vegetables (p = 0.01) was significantly associated with subjects’ meal
energy. Subconsciously, platescapes and foodscapes affect an individual’s
energy intake, and thus these elements should be considered in assessing
one’s dietary consumption.
PMID- 29941849
TI - Tetramethylpyrazine-Inducible Promoter Region from Rhodococcus jostii TMP1.
AB - An inducible promoter region, PTTMP (tetramethylpyrazine [TTMP]), has been
identified upstream of the tpdABC operon, which contains the genes required for
the initial degradation of 2,3,5,6-tetramethylpyrazine in Rhodococcus jostii TMP1
bacteria. In this work, the promoter region was fused with the gene for the
enhanced green fluorescent protein (EGFP) to investigate the activity of PTTMP by
measuring the fluorescence of bacteria. The highest promoter activity was
observed when bacteria were grown in a nutrient broth (NB) medium supplemented
with 5 mM 2,3,5,6-tetramethylpyrazine for 48 h. Using a primer extension
reaction, two transcriptional start sites for tpdA were identified, and the
putative −35 and −10 promoter motifs were determined. The minimal
promoter along with two 15 bp long direct repeats and two 7 bp inverted sequences
were identified. Also, the influence of the promoter elements on the activity of
PTTMP were determined using site-directed mutagenesis. Furthermore, PTTMP was
shown to be induced by pyrazine derivatives containing methyl groups in the 2-
and 5-positions of the heterocyclic ring, in the presence of the LuxR family
transcriptional activator TpdR.
PMID- 29941850
TI - Alterations in Metabolic Status and Headshaking Behavior Following Intravenous
Administration of Hypertonic Solutions in Horses with Trigeminal-Mediated
Headshaking.
AB - Trigeminal-nerve-mediated headshaking represents a major welfare challenge for
owners and veterinarians and is caused by a low threshold firing of the
trigeminal nerve resulting in pain manifested as violent head jerking that often
terminates the horse’s career and life due to poor quality of life and
suffering. As metabolic changes such as acid-base status and electrolytes play a
role in nerve firing, this study sought to assess the effects following
administration of hypertonic solutions on headshaking behavior in affected
horses. This prospective randomized controlled crossover design utilized six
horses affected with trigeminal-mediated headshaking and three treatment groups
receiving intravenous administration of 5% dextrose solution at 2 mL/kg bwt (DS),
NaCl 7.5% at 4 mL/kg bwt (HS), or NaHCO3 8.4% at 2 mmol/kg bwt (HB). Horses were
assessed for headshaking behavior changes at times T0 (baseline, before infusion)
and T15, 30, 60, 120 min post infusion. Venous blood variables: pH, HCO3−,
standard base excess (SBE), Na+, Cl−, K+, Ca2+, Mg2+, total magnesium
(tMg), glucose, and lactate were measured at T0 (baseline, before infusion) and
T5, 15, 30, 60, 120 min post infusion. Strong ion difference (SID) and anion gap
(AG) were calculated for each time point. With HB treatment, there was greater
than 50% reduction in headshaking rate. There was an effect of time on increasing
headshaking rate. There was an effect of breed on headshaking rate. Changes in
blood parameters following DS were virtually absent. Infusion of HS caused mild
changes and did not vary much from baseline except for SID and AG. Only infusion
of HB caused blood pH and HCO3− to be outside of the physiologic range
(alkalemia and metabolic alkalosis, respectively), SBE to double or triple, AG to
decrease, and SID to increase compared to baseline. Infusion of DS was followed
by increase in blood glucose and decrease in blood Na+. Infusion of HS was
followed by increase in Na+ and Cl− and decrease in Mg2+. Infusion of HB
was followed by decrease in Mg2+. Blood tMg, K+, and Ca2+ decreased slightly, but
did not vary greatly from baseline following any of the treatments, remaining
within physiologic ranges. Changes in blood composition were transient. Among all
treatments, only HB had an effect on headshaking rate. The limited effects
following these fluids were likely due to normal mechanisms of regulation of
blood levels of pH and electrolytes. Further investigations of changes in
electrolytes that might affect nerve firing should be explored.
PMID- 29941851
TI - (+)-epi-Epoformin, a Phytotoxic Fungal Cyclohexenepoxide: Structure Activity
Relationships.
AB - (+)-epi-Epoformin (1), is a fungal cyclohexene epoxide isolated together with
diplopimarane and sphaeropsidins A and C, a nor-ent-pimarane and two pimaranes,
from the culture filtrates of Diplodia quercivora, a fungal pathogen for cork oak
in Sardinia, Italy. Compound 1 possesses a plethora of biological activities,
including antifungal, zootoxic and phytotoxic activity. The last activity and the
peculiar structural feature of 1 suggested to carry out a structure activity
relationship study, preparing eight key hemisynthetic derivatives and the
phytotoxicity was assayed. The complete spectroscopic characterization and the
activity in the etiolated wheat coleoptile bioassay of all the compounds is
reported. Most of the compounds inhibited growth and some of them had comparable
or higher activity than the natural product and the reference herbicide Logran.
As regards the structure-activity relationship, the carbonyl proved to be
essential for their activity of 1, as well as the conjugated double bond, while
the epoxide could be altered with no significant loss.
PMID- 29941852
TI - What Is the Role of Nutritional Supplements in Support of Total Hip Replacement
and Total Knee Replacement Surgeries? A Systematic Review.
AB - Nutritional supplements can influence outcomes for individuals undergoing major
surgery, particularly in older persons whose functional reserve is limited.
Accelerating recovery from total hip replacement (THR) and total knee replacement
(TKR) may offer significant benefits. Therefore, we explored the role of
nutritional supplements in improving recovery following THR and TKR. A systematic
review was conducted to source randomized clinical trials that tested nutritional
supplements in cohorts of THR or TKR patients. Our search yielded nine relevant
trials. Intake of a carbohydrate-containing fluid is reported to improve insulin
like growth factor levels, reduce hunger, nausea, and length of stay, and
attenuate the decrease in whole-body insulin sensitivity and endogenous glucose
release. Amino acid supplementation is reported to reduce muscle atrophy and
accelerate return of functional mobility. One paper reported a suppressive effect
of beta-hydroxy beta-methylbutyrate, L-arginine, and L-glutamine supplementation
on muscle strength loss following TKR. There is limited evidence for nutritional
supplementation in THR and TKR pathways; however, the low risk profile and
potential benefits to adjunctive treatment methods, such as exercise programs,
suggest nutritional supplements may have a role. Optimizing nutritional status
pre-operatively may help manage the surgical stress response, with a particular
benefit for undernourished, frail, or elderly individuals.
PMID- 29941853
TI - Gene Therapy for Recurrent Laryngeal Nerve Injury.
AB - Recurrent laryngeal nerve (RLN) injury has considerable clinical implications,
including voice and swallowing dysfunction, which may considerably impair the
patient’s quality of life. Recovery of vocal fold movement is an essential
novel treatment option for RLN injury. The potential of gene therapy for
addressing this issue is highly promising. The target sites for RLN gene therapy
are the central nervous system, nerve fibers, laryngeal muscles, and vocal cord
mucosa. Gene transduction has been reported in each site using viral or non-viral
methods. The major issues ensuing after RLN injury are loss of motoneurons in the
nucleus ambiguus, degeneration and poor regeneration of nerve fibers and motor
end plates, and laryngeal muscle atrophy. Gene therapy using neurotrophic factors
has been assessed for most of these issues, and its efficacy has been reported.
Another important matter for functional vocal fold movement recovery is
misdirected regeneration, in which the wrong neurons may innervate other
laryngeal muscles, where even if innervation is reestablished, proper motor
function is not restored. Novel strategies involving gene therapy bear promise
for overcoming this issue and further investigations are underway.
PMID- 29941856
TI - Does the Effort Meet the Challenge in Promoting Low-Carbon City?-A Perspective of
Global Practice.
AB - Global warming caused by carbon emissions has been recognized as a challenge to
human sustainable development, and low-carbon city development is widely
considered as an effective strategy to address this challenge. Numerous emission
reduction measures have been implemented, and considerable efforts have been
devoted in promoting low-carbon city. This paper examines whether sufficient
efforts have been paid to these typical emission sectors, including Building,
Industry, Energy Transformation, and Transportation by referring to the shared
responsibility of each sector. The shared responsibility of individual emission
sector is calculated by applying energy consumption data in 2014 World Energy
Balance. The efforts contributed in emission reduction by each sector are
examined by analyzing the low-carbon city work plans of 24 representative sample
cities, which are selected globally. The research results demonstrate that
sufficient emission reduction efforts have been paid in the Building sector and
Transportation sector. But the Industry sector and Energy Transformation sector
are less-attended in addressing emission reduction. The reason for the sufficient
efforts paid in the Building sector and Transportation sector is considered as
that the efforts for emission reduction in these two sectors can bring more co
benefits. However, emission reduction in Industrial sector is generally
considered to have the effects of holding back economic growth, and the emission
reduction in the sector of Energy Transformation will need enormous investment
for advanced technologies. Policy for emission reduction in the Industry sector
and Energy Transformation sector is indispensable to promote low-carbon city.
This study appeals that (1) low-carbon city can be effectively implemented only
if carbon reduction policy is adopted to all industrial activities; (2) multiple
channels of financial resources should be established to support cities to
mitigate carbon emissions in Industry sector; (3) cooperation on the development
of clean energy technology between cities should be promoted; and (4) efforts
should be paid to reduce carbon emission from using traditional energy
transformation equipment by improving their efficiency.
PMID- 29941855
TI - alpha-Synuclein and Polyunsaturated Fatty Acids: Molecular Basis of the
Interaction and Implication in Neurodegeneration.
AB - alpha-Synuclein (alpha-syn) is a 140-amino acid protein, the physiological
function of which has yet to be clarified. It is involved in several
neurodegenerative disorders, and the interaction of the protein with brain lipids
plays an important role in the pathogenesis of Parkinson's disease (PD).
Polyunsaturated fatty acids (PUFA) are highly abundant in the brain where they
play critical roles in neuronal membrane fluidity and permeability, serve as
energy reserves and function as second messengers in cell signaling. PUFA
concentration and composition in the brain are altered with age when also an
increase of lipid peroxidation is observed. Considering that PD is clearly
correlated with oxidative stress, PUFA abundance and composition became of great
interest in neurodegeneration studies because of PUFA's high propensity to
oxidize. The high levels of the PUFA docosahexaenoic acid (DHA) in brain areas
containing alpha-syn inclusions in patients with PD further support the
hypothesis of possible interactions between alpha-syn and DHA. Additionally, a
possible functional role of alpha-syn in sequestering the early peroxidation
products of fatty acids was recently proposed. Here, we provide an overview of
the current knowledge regarding the molecular interactions between alpha-syn and
fatty acids and the effect exerted by the protein on their oxidative state. We
highlight recent findings supporting a neuroprotective role of the protein,
linking alpha-syn, altered lipid composition in neurodegenerative disorders and
PD development.
PMID- 29941854
TI - Acupuncture and Neural Mechanism in the Management of Low Back Pain-An Update.
AB - Within the last 10 years, the percentage of low back pain (LBP) prevalence
increased by 18%. The management and high cost of LBP put a tremendous burden on
the healthcare system. Many risk factors have been identified, such as lifestyle,
trauma, degeneration, postural impairment, and occupational related factors;
however, as high as 95% of the cases of LBP are non-specific. Currently, LBP is
treated pharmacologically. Approximately 25 to 30% of the patients develop
serious side effects, such as drowsiness and drug addiction. Spinal surgery often
does not result in a massive improvement of pain relief. Therefore, complementary
approaches are being integrated into the rehabilitation programs. These include
chiropractic therapy, physiotherapy, massage, exercise, herbal medicine and
acupuncture. Acupuncture for LBP is one of the most commonly used non
pharmacological pain-relieving techniques. This is due to its low adverse effects
and cost-effectiveness. Currently, many randomized controlled trials and clinical
research studies have produced promising results. In this article, the causes and
incidence of LBP on global health care are reviewed. The importance of treatment
by acupuncture is considered. The efforts to reveal the link between acupuncture
points and anatomical features and the neurological mechanisms that lead to
acupuncture-induced analgesic effect are reviewed.
PMID- 29941857
TI - Preparation and In-Vitro Assessment of Hierarchal Organized Antibacterial Breath
Mask Based on Polyacrylonitrile/Silver (PAN/AgNPs) Nanofiber.
AB - In this report, we designed and synthesized polyacrylonitrile/silver (PAN/AgNPs)
nanofibers via an in-situ method to obtain a washable with high-dispersed silver
nanoparticles membrane to form the hierarchically organized antibacterial mask to
prevent the two-way effect of bacteria from person to environment and environment
to person. For this objective, the electrospun PAN nanofibers were stabilized via
the heating method. Different amounts of AgNPs were loaded into the PAN
nanofibers by using silver nitrate and sodium hydroxide solutions. The basic
results showed that AgNPs was homogenously loaded in PAN nanofiber matrixes.
Furthermore, the release profile based on two-stage release theory showed that
when the negligible amount of AgNPs was loaded into the nanofibers, the release
significantly decreased, whereas antibacterial activity increased. The greatest
potential antibacterial activity of the lowest amount of AgNPs showed
controllable AgNPs release from PAN nanofibers that has a direct relationship
with the washability and could promote the application of the produced product.
PMID- 29941859
TI - Effect of Polyacrylic Acid on Rheology of Cement Paste Plasticized by
Polycarboxylate Superplasticizer.
AB - Viscosity-enhancing agents (VEA) have been widely employed in high flowability
cement-based materials, so as to ensure that no bleeding and segregation would
occur. However, in most cases, interaction between VEA and superplasticizer would
be unavoidable. In this study, the effect of polyacrylic acid (PAA), known as one
of the most commonly used VEAs, on rheology performance of cement paste
containing polycarboxylate superplasticizer (PCE), was studied. The initial
fluidity was assessed with mini slump, and rheological behavior of cement paste
was evaluated with rotor rheometer. Adsorption amount was examined with total
organic carbon (TOC) analyzer, and the zeta potential was also tested. The
interaction between PAA and PCE in the presence of calcium ion (Ca2+) was
analyzed with conductivity, X-ray photoelectron spectroscope (XPS), and dynamic
light scattering (DLS). The results illustrate that PAA can adsorb onto the
surface of cement particles to plasticize cement paste, being similar to PCE. In
the presence of Ca2+, PAA can be curled and crosslinked, as a result of the
combination between carboxyl groups (COO−) and Ca2+, thereby affecting the
adsorption performance and conformation behavior. It is interesting that negative
impact of PAA on dispersion efficiency of PCE can be demonstrated; one reason is
the reduced adsorption amount of PCE by PAA competitively adsorbing onto the
cement surface, and another possible reason is the invalided PCE by adsorption of
PAA. Additionally, molecular weight of PAA should be considered if being used as
VEA in PCE system.
PMID- 29941858
TI - The Role of aDNA in Understanding the Coevolutionary Patterns of Human Sexually
Transmitted Infections.
AB - Analysis of pathogen genome data sequenced from clinical and historical samples
has made it possible to perform phylogenetic analyses of sexually transmitted
infections on a global scale, and to estimate the diversity, distribution, and
coevolutionary host relationships of these pathogens, providing insights into
pathogen emergence and disease prevention. Deep-sequenced pathogen genomes from
clinical studies and ancient samples yield estimates of within-host and between
host evolutionary rates and provide data on changes in pathogen genomic stability
and evolutionary responses. Here we examine three groups of pathogens transmitted
mainly through sexual contact between modern humans to provide insight into
ancient human behavior and history with their pathogens. Exploring ancient
pathogen genomic divergence and the ancient viral-host parallel evolutionary
histories will help us to reconstruct the origin of present-day geographical
distribution and diversity of clinical pathogen infections, and will hopefully
allow us to foresee possible environmentally induced pathogen evolutionary
responses. Lastly, we emphasize that ancient pathogen DNA research should be
combined with modern clinical pathogen data, and be equitable and provide
advantages for all researchers worldwide, e.g., through shared data.
PMID- 29941860
TI - LncRNA ITGB2-AS1 Could Promote the Migration and Invasion of Breast Cancer Cells
through Up-Regulating ITGB2.
AB - In the previous study, we screened a novel lncRNA-ITGB2-AS1, which was down
regulated by bone morphogenetic protein 9 (BMP9) in breast cancer cell. Studying
ITGB2-AS1 will lay the foundation for the exploring mechanism of the BMP9
inhibitory effect on breast cancer. The expression analysis related to ITGB2-AS1
in clinical samples was conducted on online websites. The overexpression plasmid
or siRNA fragment was transfected into breast cancer cells to alter its gene
expression. The MTT assay and flow cytometry were used to measure cell viability
and cell cycle. Additionally, cell migration and invasion were detected by wound
healing and transwell assay. The results of biological function experiments
showed that ITGB2-AS1 could promote the migration and invasion of breast cancer.
Furthermore, ITGB2-AS1 increased the mRNA and protein expression of ITGB2.
Consistent with ITGB2-AS1, ITGB2 exerted the promotion effect on the migration
and invasion of breast cancer and activated integrin-related FAK signaling. The
OL plasmid expressing the truncation of ITGB2-AS1, which was complementary to
ITGB2, was essential for activation of FAK signaling. In conclusion, LncRNA ITGB2
AS1 could promote the migration and invasion of breast cancer cells by up
regulating ITGB2.
PMID- 29941861
TI - Comparison of Efficacy Outcomes of Lidocaine Spray, Topical Lidocaine Injection,
and Lidocaine General Anesthesia in Nasal Bone Fractures Surgeries: A Randomized,
Controlled Trial.
AB - BACKGROUND Lidocaine is widely used as a general and local anesthetic in minor or
major surgeries. The objective of the study was to compare postoperative pain
relief and adverse events using different forms of lidocaine administration in
patients following closed nasal bone reduction surgery. MATERIAL AND METHODS A
total of 381 patients with a solitary nasal fracture that could be managed with
closed reduction were included in this study and divided into 3 groups of 127
patients in each group. Patients had received 1% lidocaine HCl with epinephrine
(LL group), inserted a mesh impregnated with lidocaine spray (TL group), or 1
mg/kg/h lidocaine infusion (GL group) before surgeries. Patients also received
morphine when the pain was not controlled. The postoperative pain was assessed at
6 hours and 48 hours after surgery. Postoperative vomiting and nausea were
evaluated. Repeated ANOVA/Tukey-Kramer multiple comparisons test was performed at
95% confidence level. RESULTS At 6 hours after surgery, patients in the general
lidocaine (GL) group reported decreased postoperative pain compared with those in
the topical lidocaine (TL) group (P<0.001, q=6.633) and LL group (P<0.001,
q=8.056). The morphine consumption within 48 hours was least in GL group than TL
group (P<0.001, q=172.9) and LL group (P<0.001, q=226.42). Lidocaine infusion
caused nausea (P<0.001, q=6.742) and vomiting (P<0.001, q=4.306). CONCLUSIONS
Topical lidocaine anesthesia had the same postoperative pain relief and the least
adverse events as local and general lidocaine anesthesia.
PMID- 29941863
TI - Pancreas Donor Risk Index but Not Pre-Procurement Pancreas Allocation Suitability
Score Predicts Pancreas Graft Survival: A Cohort Study from a Large German
Pancreas Transplantation Center.
AB - BACKGROUND The pre-procurement pancreas allocation suitability score (P-PASS) was
introduced to support clinical decision-making and ultimately expand the
currently insufficient pancreas donor pool. The pancreas donor risk index (PDRI)
can be used at the time of organ offering to predict one-year graft survival.
Thus, this study aimed to analyze the validity of the PDRI and P-PASS in a large
German transplant center. MATERIAL AND METHODS From 2002 to 2015, we performed
327 pancreas transplantations at our center. P-PASS and PDRI were calculated for
322 patients. To evaluate the pancreas graft survival, the patient cohort was
divided into 2 P-PASS (<17, n=115 and >=17, n=207) and 3 PDRI groups (<1, n=87; 1
1.5, n=133; and >1.5, n=102). Kaplan-Meier and Cox regression analyses were
performed. We also examined differences regarding early pancreas graft failure
for both scores using the chi-square test. RESULTS The PDRI was associated with
pancreas graft survival in the univariate analysis (p=0.023). In the multivariate
analysis, a PDRI >1.5 was associated with significantly decreased graft survival
(hazard ratio=1.792, 95% confidence interval=1.10-2.90, p=0.018). The P-PASS
showed no significant association (p=0.081) with pancreas graft survival in the
Kaplan-Meier survival analysis. There were significantly more early pancreas
graft losses in the P-PASS >=17 group (p=0.025). CONCLUSIONS Our results showed
an association between P-PASS >=17 and early pancreas graft failure. However,
this does not apply to long-term pancreas graft survival; the PDRI proved to be a
better tool for this, and PDRI values >1.5 were associated with significantly
worse outcomes after pancreas transplantation.
PMID- 29941862
TI - The Presence of Coexisting Lung Cancer and Non-Tuberculous Mycobacterium in a
Solitary Mass.
AB - BACKGROUND Whereas non-tuberculous mycobacterium (NTM) pulmonary disease can
mimic lung cancer as a solitary pulmonary nodule or mass, the coexistence of lung
cancer and NTM pulmonary disease in a single nodule or mass is rare. We report
such a rare case, highlighting that during a bronchoscopes examination which
comprises taking a transbronchial lung biopsy (TBLB), bronchial brushing, and
bronchial lavage, a positive mycobacterium culture result for sputum or bronchial
lavage fluid does not exclude the possibility of a concomitant lung cancer. CASE
REPORT An 87-year-old male was referred to our institution for evaluation of an
abnormal shadow on a chest x-ray scan. He had been previously healthy with no
symptoms and an unremarkable medical history. A contrast-enhanced CT scan showed
a cavitating mass measuring 20*40 mm with a thick ring-enhancing irregular wall
in the left lower lobe. Although the TBLB of the lesion showed no malignant
cells, sputum acid-fast bacilli smear and culture of the bronchial lavage fluid
yielded positive results. An NTM infection, instead of lung cancer was suspected
to have caused the mass because a Mycobacterium tuberculosis polymerase chain
reaction showed negative results. However, we performed the surgery because NTM
pulmonary disease and lung cancer cannot be differentiated. The results of a
pathological examination of the mass showed an adenocarcinoma, and M. avium
complex was detected in the cancer tissue culture. CONCLUSIONS Physicians should
suspect the co-existent lung cancer and NTM infection in patients with solitary
lung masses that yield a positive mycobacterium culture result for sputum or
bronchial lavage fluid.
PMID- 29941864
TI - [Population impact of nurses in care interventions chronicity in Spain.
Systematic review].
AB - BACKGROUND: Epidemiological projections for the coming decades suggest that most
chronic diseases will increase its prevalence. Different models of care have been
developed to meet the challenge of chronicity; all implemented initiatives point
to primary health care and especially the community nurse as the guarantors of
chronic patient care, family and community. However, health policies do not
endorse facts. The objective of this review was to evaluate the impact of
different nursing interventions in the care strategy to chronicity in Spain.
METHODS: Systematic review of the literature on the nurse contribution to address
the chronicity in adult patients in Spain. The search was carried out in Medline
/ Pubmed, Cochrane, EMBASE, LILACS, CINAHL, IME and CUIDEN, databases. Inclusion
criteria: written articles in Castilian and English published between 2007 and
2016 involving patients with chronic disease in all their life stages. The
quality of the studies was assessed following Prisma criteria and the CEBM levels
of evidence and recommendation. RESULTS: The Nursing interventions with the
highest impact on the strategy of chronicity care in Spain were cases management
and advanced nursing practice (50%), the home-care program offered from Primary
Care (41,7%) and Telemonitoring intervention (8,3%). CONCLUSIONS: Nurses
interventions have shown favorable results in effectiveness and satisfaction more
studies that demonstrate the efficiency of the nurse contribution to the
chronicity are needed.
PMID- 29941865
TI - Structural bases of TRP channel TRPV6 allosteric modulation by 2-APB.
AB - Transient receptor potential (TRP) channels are involved in various physiological
processes, including sensory transduction. The TRP channel TRPV6 mediates calcium
uptake in epithelia and its expression is dramatically increased in numerous
types of cancer. TRPV6 inhibitors suppress tumor growth, but the molecular
mechanism of inhibition remains unknown. Here, we present crystal and cryo-EM
structures of human and rat TRPV6 bound to 2-aminoethoxydiphenyl borate (2-APB),
a TRPV6 inhibitor and modulator of numerous TRP channels. 2-APB binds to TRPV6 in
a pocket formed by the cytoplasmic half of the S1-S4 transmembrane helix bundle.
Comparing human wild-type and high-affinity mutant Y467A structures, we show that
2-APB induces TRPV6 channel closure by modulating protein-lipid interactions.
Mutagenesis and functional analyses suggest that the identified 2-APB binding
site might be present in other members of vanilloid subfamily TRP channels. Our
findings reveal a mechanism of ion channel allosteric modulation that can be
exploited for therapeutic design.
PMID- 29941866
TI - Loss of Glis3 causes dysregulation of retrotransposon silencing and germ cell
demise in fetal mouse testis.
AB - Fetal germ cell development is regulated by an elaborate combination of cell
extrinsic and cell-intrinsic signals. Here we identify a novel role for the
Kruppel-like transcription factor Gli-Similar 3 (Glis3) in male germ cell
development in the mouse embryos. Glis3 is expressed in male germ cells during
the brief window of time prior to initiation of piRNA-dependent retrotransposon
surveillance. Disruption of Glis3 function led to a widespread reduction in
retrotransposon silencing factors, aberrant retrotransposon expression and
pronounced germ cell loss. Experimental induction of precocious Glis3 expression
in vivo before its normal expression resulted in premature expression of several
piRNA pathway members, suggesting that GLIS3 is necessary for the activation of
the retrotransposon silencing programs. Our findings reveal an unexpected role
for GLIS3 in the development of male germ cells and point to a central role for
GLIS3 in the control of retrotransposon silencing in the fetal germline.
PMID- 29941868
TI - GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and
interaction with cannabidiol.
AB - The G protein-coupled receptors 3, 6, and 12 (GPR3, GPR6, and GPR12) comprise a
family of closely related orphan receptors with no confirmed endogenous ligands.
These receptors are constitutively active and capable of signaling through G
protein-mediated and non-G protein-mediated mechanisms. These orphan receptors
have previously been reported to play important roles in many normal
physiological functions and to be involved in a variety of pathological
conditions. Although they are orphans, GPR3, GPR6, and GPR12 are phylogenetically
most closely related to the cannabinoid receptors. Using beta-arrestin2
recruitment and cAMP accumulation assays, we recently found that the
nonpsychoactive phytocannabinoid cannabidiol (CBD) is an inverse agonist for
GPR3, GPR6, and GPR12. This discovery highlights these orphan receptors as
potential new molecular targets for CBD, provides novel mechanisms of action, and
suggests new therapeutic uses of CBD for illnesses such as Alzheimer's disease,
Parkinson's disease, cancer, and infertility. Furthermore, identification of CBD
as a new inverse agonist for GPR3, GPR6, and GPR12 provides the initial chemical
scaffolds upon which potent and efficacious agents acting on these receptors can
be developed, with the goal of developing chemical tools for studying these
orphan receptors and ultimately new therapeutic agents.
PMID- 29941867
TI - Association of microRNA-7 and its binding partner CDR1-AS with the prognosis and
prediction of 1st-line tamoxifen therapy in breast cancer.
AB - The large number of non-coding RNAs (ncRNAs) and their breadth of functionalities
has fuelled many studies on their roles in cancer. We previously linked four
microRNAs to breast cancer prognosis. One of these microRNAs, hsa-miR-7, was
found to be regulated by another type of ncRNA, the circular non-coding RNA
(circRNA) CDR1-AS, which contains multiple hsa-miR-7 binding sites. Based on this
finding, we studied the potential clinical value of this circRNA on breast cancer
prognosis in a cohort based on a cohort that was previously analysed for hsa-miR
7 and in an adjuvant hormone-naive cohort for 1st-line tamoxifen treatment
outcomes, in which we also analysed hsa-miR-7. A negative correlation was
observed between hsa-miR-7 and CDR1-AS in both cohorts. Despite associations with
various clinical metrics (e.g., tumour grade, tumour size, and relapse location),
CDR1-AS was neither prognostic nor predictive of relevant outcomes in our
cohorts. However, we did observe stromal CDR1-AS expression, suggesting a
possible cell-type specific interaction. Next to the known association of hsa-miR
7 expression with poor prognosis in primary breast cancer, we found that high hsa
miR-7 expression was predictive of an adverse response to tamoxifen therapy and
poor progression-free and post-relapse overall survival in patients with
recurrent disease.
PMID- 29941869
TI - Magnesium lithospermate B improves the gut microbiome and bile acid metabolic
profiles in a mouse model of diabetic nephropathy.
AB - Magnesium lithospermate B (MLB) is a new drug marketed in China to treat angina,
but its low oral bioavailability limits its clinical application to the
intravenous route. Paradoxically, orally administered low-dose MLB was found to
alleviate kidney injury in diabetic nephropathy (DN) rats, but its mechanism of
action remains unknown. In recent years, the kidney-gut axis has been suspected
to be involved in kidney damage pathogenesis, potentially representing a non
classical pathway for pharmacologic intervention. To ascertain whether MLB
targets the kidney-gut axis, streptozotocin (STZ)-treated mice were prepared as a
mouse model of DN. The STZ mice were treated with MLB (50 mg kg-1 d-1, p.o.) for
8 weeks. Twenty-four-hour urinary albumin was detected to mirror kidney function.
At week 4, 6, 8, feces were collected; bile acids (BAs) were quantified to
examine the alterations in the BA metabolic profiles, and bacterial 16S rRNA gene
fragments were sequenced to identify alterations in gut microbial composition. In
STZ mice, 24-h urinary albumin levels and total fecal BAs, especially cholic
acids (CAs) and deoxycholic acids (DCAs) were greatly increased, and the gut
microbiome was dramatically shifted compared with control mice. Oral
administration of MLB significantly decreased 24-h urinary albumin levels and
total BAs, CAs and DCAs, and reversed CA:TCA (taurocholic acid) and DCA:CA
ratios. It also changed the microbiome composition in STZ mice based on
operational units. Thus the therapeutic effect of MLB on kidney injury might be
attributed (at least partially) to its ability to modulate the disordered gut
microbiome and BA metabolism.
PMID- 29941870
TI - Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine
receptor CCR5.
AB - The chemokine receptor CCR5 is an important anti-HIV (human immunodeficiency
virus) drug target owning to its pivotal role in HIV-1 viral entry as a co
receptor. Here, we present a 2.9 A resolution crystal structure of CCR5 bound to
PF-232798, a second-generation oral CCR5 antagonist currently in phase II
clinical trials. PF-232798 and the marketed HIV drug maraviroc share a similar
tropane scaffold with different amino (N)- and carboxyl (C)- substituents.
Comparison of the CCR5-PF-232798 structure with the previously determined
structure of CCR5 in complex with maraviroc reveals different binding modes of
the two allosteric antagonists and subsequent conformational changes of the
receptor. Our results not only offer insights into the phenomenon that PF-232798
has higher affinity and alternative resistance profile to maraviroc, but also
will facilitate the design of new anti-HIV drugs.
PMID- 29941871
TI - DeTiN: overcoming tumor-in-normal contamination.
AB - Comparison of sequencing data from a tumor sample with data from a matched
germline control is a key step for accurate detection of somatic mutations.
Detection sensitivity for somatic variants is greatly reduced when the matched
normal sample is contaminated with tumor cells. To overcome this limitation, we
developed deTiN, a method that estimates the tumor-in-normal (TiN) contamination
level and, in cases affected by contamination, improves sensitivity by
reclassifying initially discarded variants as somatic.
PMID- 29941872
TI - A reassessment of DNA-immunoprecipitation-based genomic profiling.
AB - DNA immunoprecipitation followed by sequencing (DIP-seq) is a common enrichment
method for profiling DNA modifications in mammalian genomes. However, the results
of independent DIP-seq studies often show considerable variation between profiles
of the same genome and between profiles obtained by alternative methods. Here we
show that these differences are primarily due to the intrinsic affinity of IgG
for short unmodified DNA repeats. This pervasive experimental error accounts for
50-99% of regions identified as 'enriched' for DNA modifications in DIP-seq data.
Correction of this error profoundly altered DNA-modification profiles for
numerous cell types, including mouse embryonic stem cells, and subsequently
revealed novel associations among DNA modifications, chromatin modifications and
biological processes. We conclude that both matched input and IgG controls are
essential in order for the results of DIP-based assays to be interpreted
correctly, and that complementary, non-antibody-based techniques should be used
to validate DIP-based findings to avoid further misinterpretation of genome-wide
profiling data.
PMID- 29941873
TI - SAVER: gene expression recovery for single-cell RNA sequencing.
AB - In single-cell RNA sequencing (scRNA-seq) studies, only a small fraction of the
transcripts present in each cell are sequenced. This leads to unreliable
quantification of genes with low or moderate expression, which hinders downstream
analysis. To address this challenge, we developed SAVER (single-cell analysis via
expression recovery), an expression recovery method for unique molecule index
(UMI)-based scRNA-seq data that borrows information across genes and cells to
provide accurate expression estimates for all genes.
PMID- 29941874
TI - Renninger's Gedankenexperiment, the collapse of the wave function in a rigid
quantum metamaterial and the reality of the quantum state vector.
AB - A popular interpretation of the "collapse" of the wave function is as being the
result of a local interaction ("measurement") of the quantum system with a
macroscopic system ("detector"), with the ensuing loss of phase coherence between
macroscopically distinct components of its quantum state vector. Nevetheless as
early as in 1953 Renninger suggested a Gedankenexperiment, in which the collapse
is triggered by non-observation of one of two mutually exclusive outcomes of the
measurement, i.e., in the absence of interaction of the quantum system with the
detector. This provided a powerful argument in favour of "physical reality" of
(nonlocal) quantum state vector. In this paper we consider a possible version of
Renninger's experiment using the light propagation through a birefringent quantum
metamaterial. Its realization would provide a clear visualization of a wave
function collapse produced by a "non-measurement", and make the concept of a
physically real quantum state vector more acceptable.
PMID- 29941876
TI - Author Correction: Effects of Mesenchymal Stem Cell-Derived Exosomes on
Experimental Autoimmune Uveitis.
AB - A correction to this article has been published and is linked from the HTML and
PDF versions of this paper. The error has not been fixed in the paper.
PMID- 29941875
TI - Gut microbiota components are associated with fixed airway obstruction in
asthmatic patients living in the tropics.
AB - Microbiome composition has been associated to several inflammatory diseases,
including asthma. There are few studies exploring the relationships of gut
microbiota with airway obstruction pheonotypes in adult asthma, especially those
living in the tropics. We sought to evaluate the relationships of gut microbiota
with the airway obstruction and other variables of interest in asthmatic patients
living in the tropics according to three phenotypes: No Airway Obstruction (NAO),
Reversible Airway Obstruction (RAO) or Fixed Airway Obstruction (FAO). We found
that Streptococcaceae:Streptococcus and Enterobacteriaceae:Escherichia-Shigella
consistently discriminated asthmatic individuals suffering FAO from NAO or RAO,
plus Veillonellaceae:Megasphaera when comparing FAO and RAO (p < 0.05; FDR <
0.05). In the FAO, the network showing the genus relations was less complex and
interconnected. Several Rumminococcaceae, Lachnospiraceae and Clostridiales were
enriched in patients with low specific IgE levels to mites and Ascaris. All
patients shared a common exposure framework; control medication usage and smoking
habit were uncommon and equally distributed between them. In conclusion, in this
tropical asthmatic population, components of human gut microbiota are associated
with the presence of a FAO phenotype and lower specific IgE response to mites and
Ascaris.
PMID- 29941877
TI - A new role for ERG.
PMID- 29941878
TI - Maternal Trophic Status and Offpsring Phenotype in a Marine Invertebrate.
AB - Offspring size variation in relation to maternal size and season is
characteristic of a range of species living in seasonal environments. Little is
known about the proximate mechanisms explaining the links between maternally
driven variation in offspring phenotypes, for instance when mothers have
different diets depending on their size or the season. Here, we use stable
isotopes techniques to quantify size dependent and seasonal variations in diet in
mothers of shrimp Palaemon serratus and explore possible links between maternal
diet and phenotype of embryos and freshly hatched larvae. We found that larger
females, which occur more frequently in winter, produce larvae with higher carbon
and nitrogen content as well as higher percent carbon, than smaller mothers
collected in winter. In addition, isotopic composition suggest that larger
mothers collected in winter, were feeding at a higher trophic level, or on an
enriched prey pool compared with smaller mothers collected in summer. Overall,
there seems to be a strong association between offspring size and maternal diet,
mediated by maternal size and/or season.
PMID- 29941879
TI - TNF inhibits catecholamine production from induced sympathetic neuron-like cells
in rheumatoid arthritis and osteoarthritis in vitro.
AB - Synovial adipose stem cells (sASC) can be differentiated into catecholamine
expressing sympathetic neuron-like cells to treat experimental arthritis.
However, the pro-inflammatory tumor necrosis factor (TNF) is known to be toxic to
catecholaminergic cells (see Parkinson disease), and this may prevent anti
inflammatory effects in inflamed tissue. We hypothesized that TNF exhibits
inhibitory effects on human differentiated sympathetic tyrosine hydroxylase
positive (TH+) neuron-like cells. For the first time, iTH+ neuron-like
sympathetic cells were generated from sACSs of rheumatoid arthritis (RA) and
osteoarthritis (OA) synovial tissue. Compared to untreated controls in both OA
and RA, TNF-treated iTH+ cells demonstrated a weaker staining of
catecholaminergic markers in cell cultures of RA/OA patients, and the amount of
produced noradrenaline was markedly lower. These effects were reversed by
etanercept. Exposure of iTH+ cells to synovial fluid of RA patients showed
similar inhibitory effects. In mixed synovial cells, significant effects of TNF
on catecholamine release were observed only in OA. This study shows that TNF
inhibits iTH+ synovial cells leading to the decrease of secreted noradrenaline.
This might be a reason why discovered newly appearing TH+ cells in the synovium
are not able to develop their possible full anti-inflammatory role in arthritis.
PMID- 29941880
TI - Comparative study of plasmonic antennas fabricated by electron beam and focused
ion beam lithography.
AB - We present a comparative study of plasmonic antennas fabricated by electron beam
lithography and direct focused ion beam milling. We have investigated optical and
structural properties and chemical composition of gold disc-shaped plasmonic
antennas on a silicon nitride membrane fabricated by both methods to identify
their advantages and disadvantages. Plasmonic antennas were characterized using
transmission electron microscopy including electron energy loss spectroscopy and
energy dispersive X-ray spectroscopy, and atomic force microscopy. We have found
stronger plasmonic response with better field confinement in the antennas
fabricated by electron beam lithography, which is attributed to their better
structural quality, homogeneous thickness, and only moderate contamination mostly
of organic nature. Plasmonic antennas fabricated by focused ion beam lithography
feature weaker plasmonic response, lower structural quality with pronounced
thickness fluctuations, and strong contamination, both organic and inorganic,
including implanted ions from the focused beam. While both techniques are
suitable for the fabrication of plasmonic antennas, electron beam lithography
shall be prioritized over focused ion beam lithography due to better quality and
performance of its products.
PMID- 29941881
TI - Author Correction: N-terminomics identifies Prli42 as a membrane miniprotein
conserved in Firmicutes and critical for stressosome activation in Listeria
monocytogenes.
AB - This Article contains a URL for a publically available whole-genome browser (
http://nterm.listeriomics.pasteur.fr ). However, due to technical constraint,
this website has been replaced with an alternative (
https://listeriomics.pasteur.fr ).
PMID- 29941882
TI - A comparison of the effects of agricultural pesticide uses on peripheral nerve
conduction in China.
AB - Evidence on the adverse effects of agricultural pesticide use by farmers under
the actual field conditions on their peripheral nerve conduction in China is
limited. This study was to investigate the association of agricultural pesticide
use with the abnormalities of farmers' peripheral nerve conduction based on two
rounds of conventional nerve conduction studies. The level of pesticide exposure
was assessed by measuring total amount of pesticides used by farmers in 2012. The
logistic and negative binomial regression analyses were performed on a cohort
study of 218 farmers. Results show that agricultural use of neither glyphosate
nor non-glyphosate herbicides was not found to induce the abnormalities of
farmers' peripheral nerve conduction. However, agricultural use of
organophosphorus compounds was significantly associated with increased risk of
demylination disease of peripheral nerve conduction described by the reduced
velocity. Moreover, the use of organonitrogen compounds by farmers would not only
increase risk of demylination disease but axonal damages described by the reduced
amplitude. By contrast, agricultural uses of organosulfur and pyrethroid
compounds would not induce the abnormalities of farmers' peripheral nerve
conduction. The findings demonstrated the importance of developing health
friendly pesticides to replace organophosphorus and organonitrogen insecticides
and fungicides in China.
PMID- 29941883
TI - DNA damage response induced by Etoposide promotes steroidogenesis via GADD45A in
cultured adrenal cells.
AB - Glucocorticoid production is regulated by adrenocorticotropic hormone (ACTH) via
the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway in the
adrenal cortex, but the changes in steroidogenesis associated with aging are
unknown. In this study, we show that cell-autonomous steroidogenesis is induced
by non-ACTH- mediated genotoxic stress in human adrenocortical H295R cells. Low
dose etoposide (EP) was used to induce DNA damage as a genotoxic stress, leading
to cellular senescence. We found that steroidogenesis was promoted in cells
stained with gammaH2AX, a marker of DNA damaged cells. Among stress-associated
and p53-inducible genes, the expression of GADD45A and steroidogenesis-related
genes was significantly upregulated. Immunofluorescence analysis revealed that
GADD45A accumulated in the nuclei. Metabolite assay using cultured media showed
that EP-treated cells were induced to produce and secrete considerable amounts of
glucocorticoid. Knockdown of GADD45A using small interfering RNA markedly
inhibited the EP-induced upregulation of steroidogenesis-related gene expression,
and glucocorticoid production. A p38MAPK inhibitor, but not a PKA inhibitor,
suppressed EP-stimulated steroidogenesis. These results suggest that DNA damage
itself promotes steroidogenesis via one or more unprecedented non-ACTH-mediated
pathway. Specifically, GADD45A plays a crucial role in the steroidogenic
processes triggered by EP-stimulated genotoxic stress. Our study sheds new light
on an alternate mechanism of steroidogenesis in the adrenal cortex.
PMID- 29941884
TI - Inverse association between soy food consumption, especially fermented soy
products intake and soy isoflavone, and arterial stiffness in Japanese men.
AB - Studies on the associations between soy food consumption and arterial stiffness
are rare. The aim of the present study was to evaluate their associations in
Japanese men. A total of 652 eligible men, aged 35-69 years, who underwent the
measurement of brachial-ankle pulse wave velocity (baPWV) as an index of arterial
stiffness were evaluated in this cross-sectional study. Information on their
lifestyle characteristics, including dietary behavior, was obtained from a
structured self-administered questionnaire. The frequency of total soy products
as well as fermented and non-fermented soy products intakes was calculated, and
the amounts of soy protein and soy isoflavone intakes were also estimated; these
were then divided into tertiles and their associations with baPWV values were
evaluated using general linear models. Higher frequency of fermented soy products
intake was associated with decreased baPWV after adjusting for the multivariable
covariates (P value for trend was 0.002, in Model 3). This association did not
alter after further adjustment with a biomarker of systemic inflammation (serum
high-sensitivity C-reactive protein (hs-CRP)) (P value for trend was 0.001, in
Model 4). Total soy isoflavone consumption was also inversely associated with
baPWV even after adjusting for multivariable covariates including serum hs-CRP (P
value for trend was 0.043, in Model 4); however total soy protein consumption was
not. These results demonstrated that greater consumption of soy food, especially
fermented soy products and soy isoflavone was associated with reduced arterial
stiffness, independent of systemic inflammation, in Japanese men.
PMID- 29941885
TI - Antifungal tolerance is a subpopulation effect distinct from resistance and is
associated with persistent candidemia.
AB - Tolerance to antifungal drug concentrations above the minimal inhibitory
concentration (MIC) is rarely quantified, and current clinical recommendations
suggest it should be ignored. Here, we quantify antifungal tolerance in Candida
albicans isolates as the fraction of growth above the MIC, and find that it is
distinct from susceptibility/resistance. Instead, tolerance is due to the slow
growth of subpopulations of cells that overcome drug stress more efficiently than
the rest of the population, and correlates inversely with intracellular drug
accumulation. Many adjuvant drugs used in combination with fluconazole, a widely
used fungistatic drug, reduce tolerance without affecting resistance.
Accordingly, in an invertebrate infection model, adjuvant combination therapy is
more effective than fluconazole in treating infections with highly tolerant
isolates and does not affect infections with low tolerance isolates. Furthermore,
isolates recovered from immunocompetent patients with persistent candidemia
display higher tolerance than isolates readily cleared by fluconazole. Thus,
tolerance correlates with, and may help predict, patient responses to fluconazole
therapy.
PMID- 29941886
TI - Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell
migration.
AB - Dendritic cells (DCs) are first responders of the innate immune system that
integrate signals from external stimuli to direct context-specific immune
responses. Current models suggest that an active switch from mitochondrial
metabolism to glycolysis accompanies DC activation to support the anabolic
requirements of DC function. We show that early glycolytic activation is a common
program for both strong and weak stimuli, but that weakly activated DCs lack long
term HIF-1alpha-dependent glycolytic reprogramming and retain mitochondrial
oxidative metabolism. Early induction of glycolysis is associated with activation
of AKT, TBK, and mTOR, and sustained activation of these pathways is associated
with long-term glycolytic reprogramming. We show that inhibition of glycolysis
impaired maintenance of elongated cell shape, DC motility, CCR7 oligomerization,
and DC migration to draining lymph nodes. Together, our results indicate that
early induction of glycolysis occurs independent of pro-inflammatory phenotype,
and that glycolysis supports DC migratory ability regardless of mitochondrial
bioenergetics.
PMID- 29941887
TI - A heterogeneous single-atom palladium catalyst surpassing homogeneous systems for
Suzuki coupling.
AB - Palladium-catalysed cross-coupling reactions, central tools in fine-chemical
synthesis, predominantly employ soluble metal complexes despite recognized
challenges with product purification and catalyst reusability1-3. Attempts to
tether these homogeneous catalysts on insoluble carriers have been thwarted by
suboptimal stability, which leads to a progressively worsening performance due to
metal leaching or clustering4. The alternative application of supported Pd
nanoparticles has faced limitations because of insufficient activity under the
mild conditions required to avoid thermal degradation of the substrates or
products. Single-atom heterogeneous catalysts lie at the frontier5-18. Here, we
show that the Pd atoms anchored on exfoliated graphitic carbon nitride (Pd-ECN)
capture the advantages of both worlds, as they comprise a solid catalyst that
matches the high chemoselectivity and broad functional group tolerance of state
of-the-art homogeneous catalysts for Suzuki couplings, and also demonstrate a
robust stability in flow. The adaptive coordination environment within the
macroheterocycles of ECN facilitates each catalytic step. The findings illustrate
the exciting opportunities presented by nanostructuring single atoms in solid
hosts for catalytic processes that remain difficult to heterogenize.
PMID- 29941888
TI - Pathway-controlled formation of mesostructured all-DNA colloids and
superstructures.
AB - DNA has traditionally been used for the programmable design of nanostructures by
exploiting its sequence-defined supramolecular recognition. However, control on
larger length scales or even hierarchical materials that translate to the
macroscale remain difficult to construct. Here, we show that the polymer
character of single-stranded DNA (ssDNA) can be activated via a nucleobase
specific lower critical solution temperature, which provides a unique access to
mesoscale structuring mechanisms on larger length scales. We integrate both
effects into ssDNA multiblock copolymers that code sequences for phase
separation, hybridization and functionalization. Kinetic pathway guidance using
temperature ramps balances the counteracting mesoscale phase separation during
heating with nanoscale duplex recognition during cooling to yield a diversity of
complex all-DNA colloids with control over the internal dynamics and of their
superstructures. Our approach provides a facile and versatile platform to add
mesostructural layers into hierarchical all-DNA materials. The high density of
addressable ssDNA blocks opens routes for applications such as gene delivery,
artificial evolution or spatially encoded (bio)materials.
PMID- 29941889
TI - Tailoring sample-wide pseudo-magnetic fields on a graphene-black phosphorus
heterostructure.
AB - Spatially tailored pseudo-magnetic fields (PMFs) can give rise to pseudo-Landau
levels and the valley Hall effect in graphene. At an experimental level, it is
highly challenging to create the specific strain texture that can generate PMFs
over large areas. Here, we report that superposing graphene on multilayer black
phosphorus creates shear-strained superlattices that generate a PMF over an
entire graphene-black phosphorus heterostructure with edge size of tens of
micrometres. The PMF is intertwined with the spatial period of the moire pattern,
and its spatial distribution and intensity can be modified by changing the
relative orientation of the two materials. We show that the emerging pseudo
Landau levels influence the transport properties of graphene-black phosphorus
field-effect transistor devices with Hall bar geometry. The application of an
external magnetic field allows us to enhance or reduce the effective field
depending on the valley polarization with the prospect of developing a valley
filter.
PMID- 29941890
TI - Transparent anti-fogging and self-cleaning TiO2/SiO2 thin films on polymer
substrates using atmospheric plasma.
AB - Transparent anti-fogging and self-cleaning coatings are of great interest for
many applications, including solar panels, windshields and displays or lenses to
be used in humid environments. In this paper, we report on the simultaneous
synthesis, at atmospheric pressure, of anatase TiO2 nanoparticles and low
temperature, high-rate deposition of anatase TiO2/SiO2 nanocomposite coatings.
These coatings exhibit durable super-hydrophilic and photocatalytic properties.
The strategy followed relies on concomitant and separated injections of titania,
i.e. titanium isopropoxide, and silica, i.e. hexamethyldisiloxane, precursors in
the stream of a blown-arc discharge to form transparent anti-fogging and self
cleaning anatase TiO2/SiO2 nanocomposite coatings on polymer substrates.
PMID- 29941891
TI - Publisher Correction: Orbital angular momentum analysis for giant spin splitting
in solids and nanostructures.
AB - A correction to this article has been published and is linked from the HTML and
PDF versions of this paper. The error has not been fixed in the paper.
PMID- 29941892
TI - Compressive response and buckling of graphene nanoribbons.
AB - We examine the mechanical response of single layer graphene nanoribbons (GNR)
under constant compressive loads through molecular dynamics simulations.
Compressive stress-strain curves are presented for GNRs of various lengths and
widths. The dependence of GNR's buckling resistance on its size, aspect ratio,
and chiral angle is discussed and approximate corresponding relations are
provided. A single master curve describing the dependence of the critical
buckling stress of GNRs on their aspect ratio is presented. Our findings were
compared to the continuum elasticity theories for wide plates and wide columns.
In the large width limit, the response of the GNRs agrees with the predictions of
the wide plates theory and thus, with that of wide graphenes. In the small width
limit, the behavior of graphene nanoribbons deviates from that of periodic
graphenes due to various edge related effects which govern the stiffness and the
stability of the graphene membranes, but it qualitatively agrees with the theory
of wide columns. In order to assess the effect of thermal fluctuations on the
critical buckling stress a wide range of temperatures is examined. The findings
of the current study could provide important insights regarding the feasibility
and the evaluation of the performance of graphene-based devices.
PMID- 29941893
TI - Characterization of influenza virus variants induced by treatment with the
endonuclease inhibitor baloxavir marboxil.
AB - Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently
and selectively inhibits the cap-dependent endonuclease within the polymerase PA
subunit of influenza A and B viruses. In clinical trials, single doses of BXM
profoundly decrease viral titers as well as alleviating influenza symptoms. Here,
we characterize the impact on BXA susceptibility and replicative capacity of
variant viruses detected in the post-treatment monitoring of the clinical
studies. We find that the PA I38T substitution is a major pathway for reduced
susceptibility to BXA, with 30- to 50-fold and 7-fold EC50 changes in A and B
viruses, respectively. The viruses harboring the I38T substitution show severely
impaired replicative fitness in cells, and correspondingly reduced endonuclease
activity in vitro. Co-crystal structures of wild-type and I38T influenza A and B
endonucleases bound to BXA show that the mutation reduces van der Waals contacts
with the inhibitor. A reduced affinity to the I38T mutant is supported by the
lower stability of the BXA-bound endonuclease. These mechanistic insights provide
markers for future surveillance of treated populations.
PMID- 29941895
TI - The Biological Object Notation (BON): a structured file format for biological
data.
AB - The large size and high complexity of biological data can represent a major
methodological challenge for the analysis and exchange of data sets between
computers and applications. There has also been a substantial increase in the
amount of metadata associated with biological data sets, which is being
increasingly incorporated into existing data formats. Despite the existence of
structured formats based on XML, biological data sets are mainly formatted using
unstructured file formats, and the incorporation of metadata results in
increasingly complex parsing routines such that they become more error prone. To
overcome these problems, we present the "biological object notation" (BON)
format, a new way to exchange and parse nearly all biological data sets more
efficiently and with less error than other currently available formats. Based on
JavaScript Object Notation (JSON), BON simplifies parsing by clearly separating
the biological data from its metadata and reduces complexity compared to XML
based formats. The ability to selectively compress data up to 87% compared to
other file formats and the reduced complexity results in improved transfer times
and less error prone applications.
PMID- 29941894
TI - Hybrids of amphibian chytrid show high virulence in native hosts.
AB - Hybridization of parasites can generate new genotypes with high virulence. The
fungal amphibian parasite Batrachochytrium dendrobatidis (Bd) hybridizes in
Brazil's Atlantic Forest, a biodiversity hotspot where amphibian declines have
been linked to Bd, but the virulence of hybrid genotypes in native hosts has
never been tested. We compared the virulence (measured as host mortality and
infection burden) of hybrid Bd genotypes to the parental lineages, the putatively
hypovirulent lineage Bd-Brazil and the hypervirulent Global Pandemic Lineage (Bd
GPL), in a panel of native Brazilian hosts. In Brachycephalus ephippium, the
hybrid exceeded the virulence (host mortality) of both parents, suggesting that
novelty arising from hybridization of Bd is a conservation concern. In
Ischnocnema parva, host mortality in the hybrid treatment was intermediate
between the parent treatments, suggesting that this species is more vulnerable to
the aggressive phenotypes associated with Bd-GPL. Dendropsophus minutus showed
low overall mortality, but infection burdens were higher in frogs treated with
hybrid and Bd-GPL genotypes than with Bd-Brazil genotypes. Our experiment
suggests that Bd hybrids have the potential to increase disease risk in native
hosts. Continued surveillance is needed to track potential spread of hybrid
genotypes and detect future genomic shifts in this dynamic disease system.
PMID- 29941896
TI - Optical Properties and Local Structure Evolution during Crystallization of
Ga16Sb84 Alloy.
AB - Phase-change memory is one of the most promising candidates for future memory
technologies. However, most of the phase-change memories are based on
chalcogenides, while other families of materials for this purpose remain
insufficiently studied. In this work, we investigate the optical properties and
microstructure of Ga16Sb84 by an in-situ ellipsometer and X-ray diffraction. Our
experimental results reveal that the Ga16Sb84 films exhibit a relatively high
crystallization temperature of ~250 degrees C, excelling in long data retention.
In addition, a large optical contrast exists between the amorphous and
crystalline states, which may make it suitable for use in optical discs.
Molecular dynamics simulations indicate that a unique local structure order in
the amorphous and crystalline phases is responsible for the optical properties
observed in the experiment. The similarity found in the short-range orders of the
amorphous and crystalline phases is beneficial to better understanding the fast
phase transition of phase-change memory.
PMID- 29941897
TI - Elastic and dynamical structural properties of La and Mn-doped SrTiO3 studied by
neutron scattering and their relation with thermal conductivities.
AB - The electron-doped SrTiO3 exhibits good thermoelectric properties, which makes
this material a promising candidate of an n-type oxide thermoelectric device.
Recent studies indicated that only a few percent co-doping of La and Mn in SrTiO3
substantially reduces the thermal conductivity, thereby greatly improving the
thermoelectric figure of merit at room temperature. Our time-of-flight neutron
scattering studies revealed that by doping both La and Mn into SrTiO3, the
inelastic scattering spectrum shows a momentum-independent increase in the low
energy spectral weight approximately below 10 meV. The increase in the low-energy
spectral weight exhibits a clear correlation with thermal conductivity. The
correlation is attributed to dynamical and local structural fluctuations caused
by the Jahn-Teller instability in Mn3+ ions coupled with the incipient
ferroelectric nature of SrTiO3, as the origin of the low thermal conductivity.
PMID- 29941898
TI - Correction: Prediction of preterm birth with and without preeclampsia using mid
pregnancy immune and growth-related molecular factors and maternal
characteristics.
AB - This Article was originally published under Nature Research's License to Publish,
but has nowbeen made available under a [CC BY 4.0] license. The PDF and HTML
versions of the Articlehave been modified accordingly.
PMID- 29941899
TI - Lessons for cancer drug treatment from tackling a non-cancerous overgrowth
syndrome.
PMID- 29941900
TI - Twenty years of network science.
PMID- 29941901
TI - Weighing in on weight loss in pancreatic cancer.
PMID- 29941903
TI - Topological light-trapping on a dislocation.
AB - Topological insulators have unconventional gapless edge states where disorder
induced back-scattering is suppressed. In photonics, such edge states lead to
unidirectional waveguides which are useful for integrated photonic circuitry.
Cavity modes, another type of fundamental component in photonic chips, however,
are not protected by band topology because of their lower dimensions. Here we
demonstrate that concurrent wavevector space and real-space topology, dubbed as
dual-topology, can lead to light-trapping in lower dimensions. The resultant
photonic-bound state emerges as a Jackiw-Rebbi soliton mode localized on a
dislocation in a two-dimensional photonic crystal, as proposed theoretically and
discovered experimentally. Such a strongly confined cavity mode is found to be
robust against perturbations. Our study unveils a mechanism for topological light
trapping in lower dimensions, which is invaluable for fundamental physics and
various applications in photonics.
PMID- 29941904
TI - Non-aqueous homogenous biocatalytic conversion of polysaccharides in ionic
liquids using chemically modified glucosidase.
AB - The increasing requirement to produce platform chemicals and fuels from renewable
sources means advances in biocatalysis are rapidly becoming a necessity. Biomass
is widely used in nature as a source of energy and as chemical building blocks.
However, recalcitrance towards traditional chemical processes and solvents
provides a significant barrier to widespread utility. Here, by optimizing enzyme
solubility in ionic liquids, we have discovered solvent-induced substrate
promiscuity of glucosidase, demonstrating an unprecedented example of homogeneous
enzyme bioprocessing of cellulose. Specifically, chemical modification of
glucosidase for solubilization in ionic liquids can increase thermal stability to
up to 137 degrees C, allowing for enzymatic activity 30 times greater than is
possible in aqueous media. These results establish that through a synergistic
combination of chemical biology (enzyme modification) and reaction engineering
(solvent choice), the biocatalytic capability of enzymes can be intensified: a
key step towards the full-scale deployment of industrial biocatalysis.
PMID- 29941905
TI - Structure-performance descriptors and the role of Lewis acidity in the methanol
to-propylene process.
AB - The combination of well-defined acid sites, shape-selective properties and
outstanding stability places zeolites among the most practically relevant
heterogeneous catalysts. The development of structure-performance descriptors for
processes that they catalyse has been a matter of intense debate, both in
industry and academia, and the direct conversion of methanol to olefins is a
prototypical system in which various catalytic functions contribute to the
overall performance. Propylene selectivity and resistance to coking are the two
most important parameters in developing new methanol-to-olefin catalysts. Here,
we present a systematic investigation on the effect of acidity on the performance
of the zeolite 'ZSM-5' for the production of propylene. Our results demonstrate
that the isolation of Bronsted acid sites is key to the selective formation of
propylene. Also, the introduction of Lewis acid sites prevents the formation of
coke, hence drastically increasing catalyst lifetime.
PMID- 29941906
TI - Complementary site-selectivity in arene functionalization enabled by overcoming
the ortho constraint in palladium/norbornene catalysis.
AB - Achieving site-selectivity in arene functionalization that is complementary to
the site-selectivity from electrophilic aromatic substitution reactions has been
a long-standing quest in organic synthesis. Palladium/norbornene cooperative
catalysis potentially offers a unique approach to this problem, but its use has
been hampered by the ortho constraint, which is the requirement of an ortho
substituent for mono ortho functionalization of haloarenes. Here, we show that
such a challenge could be addressed using a new class of bridgehead-modified
norbornenes, thereby enabling a broadly useful strategy for arene
functionalization with complementary site-selectivity. A range of ortho
unsubstituted aryl iodides, previously problematic substrates, can now be
employed to provide mono ortho-functionalized products effectively. This method
is applicable for late-stage functionalization of complex bioactive molecules at
positions that are difficult to reach by conventional approaches.
PMID- 29941907
TI - Brittle-star mass occurrence on a Late Cretaceous methane seep from South Dakota,
USA.
AB - Articulated brittle stars are rare fossils because the skeleton rapidly
disintegrates after death and only fossilises intact under special conditions.
Here, we describe an extraordinary mass occurrence of the ophiacanthid ophiuroid
Brezinacantha tolis gen. et sp. nov., preserved as articulated skeletons from an
upper Campanian (Late Cretaceous) methane seep of South Dakota. It is uniquely
the first fossil case of a seep-associated ophiuroid. The articulated skeletons
overlie centimeter-thick accumulations of dissociated skeletal parts, suggesting
lifetime densities of approximately 1000 individuals per m2, persisting at that
particular location for several generations. The ophiuroid skeletons on top of
the occurrence were preserved intact most probably because of increased methane
seepage, killing the individuals and inducing rapid cementation, rather than due
to storm-induced burial or slumping. The mass occurrence described herein is an
unambiguous case of an autochthonous, dense ophiuroid community that persisted at
a particular spot for some time. Thus, it represents a true fossil equivalent of
a recent ophiuroid dense bed, unlike other cases that were used in the past to
substantiate the claim of a mid-Mesozoic predation-induced decline of ophiuroid
dense beds.
PMID- 29941908
TI - Ablation of Runx2 in Ameloblasts Suppresses Enamel Maturation in Tooth
Development.
AB - Runt-related transcription factor 2 (Runx2) is involved in the early stage of
tooth development. However, only few studies have reported the role of Runx2 in
enamel development, which may be attributed to that Runx2 full knockout mice
cannot survive after birth. In the present study, we successfully established a
Runx2-deficient mouse model using a conditional knockout (cKO) method. We
observed a significant reduction in the degree of mineralization and the
decreased size of enamel rods in cKO mice. Histological analysis showed the
retained enamel proteins in enamel layer at maturation stage in cKO molars.
Further analysis by qRT-PCR revealed that the expressions of genes encoding
enamel structure proteins, such as amelogenin (AMELX), ameloblastin (AMBN) and
enamelin (ENAM), were increased in cKO enamel organs. On the other hand, the
expression of kallikrein-related peptidase-4 (KLK4) at the mRNA and protein
levels was dramatically decreased from late secretory stage to maturation stage
in cKO enamel organs, while the expression of matrix metalloproteinase-20 (MMP
20) was not significantly altered. Finally, immunohistochemistry indicated that
the uptake of amelogenins by ameloblasts was significantly decreased in cKO mice.
Taken together, Runx2 played critical roles in controlling enamel maturation by
increasing synthesis of KLK4 and decreasing synthesis of AMELX, AMBN and ENAM.
PMID- 29941909
TI - Dalbavancin for treatment of implant-related methicillin-resistant Staphylococcus
aureus osteomyelitis in an experimental rat model.
AB - Dalbavancin is a new semisynthetic lipoglycopeptide with improved antimicrobial
activity against various gram-positive pathogens. It demonstrates an extensive
plasma half-life which permits outpatient parenteral antimicrobial therapy with
weekly intervals and might therefore be an excellent treatment alternative for
patients requiring prolonged antimicrobial therapy. The present study
investigated dalbavancin monotherapy in an experimental implant-related
methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model. A
clinical MRSA isolate and a Kirschner-wire were inserted into the proximal tibia
of anaesthetized Sprague-Dawley rats. Four weeks after infection 34 animals were
treated over 4 weeks with either dalbavancin (20 mg/kg loading-dose; 10 mg/kg
daily), vancomycin (50 mg/kg twice daily) or left untreated. Twenty-four hours
after the last treatment dose tibial bones and Kirschner-wires were harvested for
microbiological examination. Based on quantitative bacterial cultures of osseous
tissue, dalbavancin was as effective as vancomycin and both were superior to no
treatment. No emergence of an induced glycopeptide-/lipoglycopeptide- resistance
was observed after a treatment period of four weeks with either dalbavancin or
vancomycin. In conclusion, monotherapy with dalbavancin was shown to be as
effective as vancomycin for treatment of experimental implant-related MRSA
osteomyelitis in rats, but both antimicrobials demonstrated only limited
efficacy. Further studies are warranted to evaluate the clinical efficacy of
dalbavancin for the treatment of periprosthetic S. aureus infections.
PMID- 29941910
TI - Sensory overamplification in layer 5 auditory corticofugal projection neurons
following cochlear nerve synaptic damage.
AB - Layer 5 (L5) cortical projection neurons innervate far-ranging brain areas to
coordinate integrative sensory processing and adaptive behaviors. Here, we
characterize a plasticity in L5 auditory cortex (ACtx) neurons that innervate the
inferior colliculus (IC), thalamus, lateral amygdala and striatum. We track daily
changes in sound processing using chronic widefield calcium imaging of L5 axon
terminals on the dorsal cap of the IC in awake, adult mice. Sound level growth
functions at the level of the auditory nerve and corticocollicular axon terminals
are both strongly depressed hours after noise-induced damage of cochlear afferent
synapses. Corticocollicular response gain rebounded above baseline levels by the
following day and remained elevated for several weeks despite a persistent
reduction in auditory nerve input. Sustained potentiation of excitatory ACtx
projection neurons that innervate multiple limbic and subcortical auditory
centers may underlie hyperexcitability and aberrant functional coupling of
distributed brain networks in tinnitus and hyperacusis.
PMID- 29941911
TI - Neck-specific exercise improves impaired interactions between ventral neck
muscles in chronic whiplash: A randomized controlled ultrasound study.
AB - Chronic pain and disability is common in whiplash-associated disorders (WAD),
leading to personal suffering, sick leave, and social cost. The cervical spine is
heavily dependent on muscular support and whiplash injury can cause damage to the
neck muscles, but diagnostic tools to measure neck muscle impairment and evaluate
exercise interventions are lacking. Therefore, the present study investigated
ventral neck muscle interactions in 26 individuals with chronic WAD randomized to
neck-specific exercise (NSE) or remaining on a waiting list (WL) in 3 months. We
performed real-time, non-invasive ultrasound measurements with speckle tracking
analysis and calculated the deformation area and deformation rate in three
ventral neck muscles. Multivariate statistics were used to analyse interactions
between the muscles. After 3 months of NSE, significant improvements were
observed in neck muscle interactions and pain intensity in the NSE group compared
to the WL group. Thus, this study demonstrates that non-invasive ultrasound can
be a diagnostic tool for muscle impairment and used to evaluate exercise
interventions in WAD and stands to make a breakthrough for better management in
chronic WAD.
PMID- 29941912
TI - Polyphenol-rich foods and risk of gestational diabetes: a systematic review and
meta-analysis.
AB - Animal studies have demonstrated anti-diabetic properties of several food-derived
polyphenols, but data in humans remains unclear. This study aimed to review and
meta-analyse evidence concerning the effect of the intake of several polyphenol
rich foods on gestational diabetes (GDM) risk. A systematic literature search was
conducted in PubMed, Web of Science and Embase databases for observational
studies on the association between dietary intake of foods/diets rich in
polyphenols and GDM risk. Inclusion criteria were original research articles with
full texts published in peer-reviewed English language journals, which
investigated foods within the top 100 richest dietary sources of polyphenols and
reported odds ratio/relative risk with their corresponding 95% confidence
intervals. The quality of included studies was assessed using the Newcastle
Ottawa Scale. The intake of polyphenol-rich foods and dietary patterns in
relation to GDM were pooled with fixed- and random-effects models. In total, 12
(10 cohort, 1 cross-sectional and 1 case-control) studies were included for the
final systematic review, comprising 124,959 participants and including 5,786
women with GDM. Five studies found a significant, inverse association between the
intake of polyphenol-rich foods or Mediterranean diet and GDM, whereas five
studies reported no association and two exhibited a positive association. Meta
analyses further showed that the risk of GDM was about halved amongst women with
the highest score of Mediterranean diet compared to those with the lowest score.
The results suggest that dietary patterns rich in polyphenols may reduce the risk
of GDM despite inconclusive evidence for polyphenol-rich food groups.
PMID- 29941913
TI - Dietary responses to a multiple sclerosis diagnosis: a qualitative study.
AB - BACKGROUND/OBJECTIVES: Multiple sclerosis (MS) is an immune-mediated disease with
no known cure and insufficient evidence to support a special therapeutic diet to
alter symptom management or disease progression. Several studies have reported
dietary changes made by people with MS, but there has been limited investigation
into experiences surrounding diet in those recently diagnosed. This study
explored responses to diet after a recent diagnosis of MS in people living in
Western Australia. SUBJECTS/METHODS: Eleven adults with MS (mean time since
diagnosis 8 months) participated in semi-structured interviews focusing on
responses to diet since MS diagnosis. Interviews were transcribed, coded and
analysed using grounded theory principles. RESULTS: Three theme responses
emerged; (1) the perceived incompatibility of lack of/or generalised dietary
advice with disease seriousness at the time of diagnosis; (2) extensive personal
research and information seeking with difficulty judging credibility, and (3)
self-experimentation with diet to either control MS symptoms or to cure MS.
CONCLUSIONS: Given the seriousness of the disease, there is a perceived gap in
dietary information provided at the time of diagnosis. Healthcare professionals
should address concerns with alternative therapeutic diets advertised to treat or
cure MS, and clearly convey the reasoning for the general healthy dietary
recommendations. This would better align advice with the perceptions about the
role of diet in MS, assist people with MS in need of information and minimise
dietary self-experimentation. Future research should explore the importance of
diet for those who have had MS for a longer period of time.
PMID- 29941914
TI - Application of Whole Genome Resequencing in Mapping of a Tomato Yellow Leaf Curl
Virus Resistance Gene.
AB - Tomato yellow leaf curl virus (TYLCV) has significantly impacted the tomato
industry around the world, and the use of insecticides and insect nets have not
effectively controlled the spread of this pathogen. The tomato line AVTO1227 is
highly resistant to TYLCV. In this study, F2 and BC1 populations derived from
AVTO1227 and the susceptible line Money maker were used to assess the genetic
mechanism underlying TYLCV resistance. We have identified a recessive TYLCV
resistance gene, hereby designated as ty-5, which is linked to SlNACI. Genomic
DNA pools from resistant and susceptible groups were constructed, and their
genomes were resequenced. The ty-5 gene was identified on an interval
encompassing the genomic positions 2.22 Mb to 3.19 Mb on tomato chromosome 4.
Genotyping using linkage markers further mapped ty-5 within the interval between
markers ty5-25 and ty5-29, where only the pelota gene is located. Consequently,
pelota was considered as the candidate gene corresponding to ty-5. Two nucleotide
transversions within the promoter region and one transversion in exon region of
the pelota gene were detected in the parental lines. However, the relative
transcript levels of pelota did not significantly differ among the three tomato
lines, regardless of TYLCV infection. This study will facilitate marker-assisted
breeding for resistance to TYLCV and lay a foundation for the research of the
resistance mechanism of ty-5 in tomato.
PMID- 29941915
TI - Direct observation of exciton-exciton interactions.
AB - Natural light harvesting as well as optoelectronic and photovoltaic devices
depend on efficient transport of energy following photoexcitation. Using common
spectroscopic methods, however, it is challenging to discriminate one-exciton
dynamics from multi-exciton interactions that arise when more than one excitation
is present in the system. Here we introduce a coherent two-dimensional
spectroscopic method that provides a signal only in case that the presence of one
exciton influences the behavior of another one. Exemplarily, we monitor exciton
diffusion by annihilation in a perylene bisimide-based J-aggregate. We determine
quantitatively the exciton diffusion constant from exciton-exciton-interaction 2D
spectra and reconstruct the annihilation-free dynamics for large pump powers. The
latter enables for ultrafast spectroscopy at much higher intensities than
conventionally possible and thus improves signal-to-noise ratios for
multichromophore systems; the former recovers spatio-temporal dynamics for a
broad range of phenomena in which exciton interactions are present.
PMID- 29941916
TI - Microstructure and mechanical properties of hard Acrocomia mexicana fruit shell.
AB - Fruit and nut shells can exhibit high hardness and toughness. In the peninsula of
Yucatan, Mexico, the fruit of the Cocoyol palm tree (Acrocomia mexicana) is well
known to be very difficult to break. Its hardness has been documented since the
1500 s, and is even mentioned in the popular Maya legend The Dwarf of Uxmal.
However, until now, no scientific studies quantifying the mechanical performance
of the Cocoyol endocarp has been found in the literature to prove or disprove
that this fruit shell is indeed "very hard". Here we report the mechanical
properties, microstructure and hardness of this material. The mechanical
measurements showed compressive strength values of up to ~150 and ~250 MPa under
quasi-static and high strain rate loading conditions, respectively, and
microhardness of up to ~0.36 GPa. Our findings reveal a complex hierarchical
structure showing that the Cocoyol shell is a functionally graded material with
distinctive layers along the radial directions. These findings demonstrate that
structure-property relationships make this material hard and tough. The
mechanical results and the microstructure presented herein encourage designing
new types of bioinspired superior synthetic materials.
PMID- 29941917
TI - A CLC-type F-/H+ antiporter in ion-swapped conformations.
AB - Fluoride/proton antiporters of the CLCF family combat F- toxicity in bacteria by
exporting this halide from the cytoplasm. These transporters belong to the
widespread CLC superfamily but display transport properties different from those
of the well-studied Cl-/H+ antiporters. Here, we report a structural and
functional investigation of these F--transport proteins. Crystal structures of a
CLCF homolog from Enterococcus casseliflavus are captured in two conformations
with simultaneous accessibility of F- and H+ ions via separate pathways on
opposite sides of the membrane. Manipulation of a key glutamate residue critical
for H+ and F- transport reverses the anion selectivity of transport; replacement
of the glutamate with glutamine or alanine completely inhibits F- and H+
transport while allowing for rapid uncoupled flux of Cl-. The structural and
functional results lead to a 'windmill' model of CLC antiport wherein F- and H+
simultaneously move through separate ion-specific pathways that switch sidedness
during the transport cycle.
PMID- 29941918
TI - Adaptable, illumination patterning light sheet microscopy.
AB - Minimally-invasive optical imaging requires that light is delivered efficiently
to limit the detrimental impact of photodamage on delicate biological systems.
Light sheet microscopy represents the exemplar in tissue specific optical imaging
of small and mesoscopic samples alike. However, further gains towards gentler
imaging require a more selective imaging strategy to limit exposure to multiple
yet discrete tissues without overexposing the sample, particularly where the
information content is sparse or particularly optically sensitive tissues are
present. The development of sample-adaptive imaging techniques is crucial in
pursuit of the next generation of smart, autonomous microscopes. Herein, we
report a microscope capable of performing 4D (x, y, z, t) light patterning to
selectively illuminate multiple, rapidly reconfigurable regions of interest while
maintaining the rapid imaging speed and high contrast associated with light sheet
microscopy. We illustrate this utility in living zebrafish larvae and phantom
samples.
PMID- 29941919
TI - N-Acyldopamine induces aggresome formation without proteasome inhibition and
enhances protein aggregation via p62/SQSTM1 expression.
AB - Accumulation of ubiquitinated protein aggregates is a common pathology associated
with a number of neurodegenerative diseases and selective autophagy plays a
critical role in their elimination. Although aging-related decreases in protein
degradation properties may enhance protein aggregation, it remains unclear
whether proteasome dysfunction is indispensable for ubiquitinated-protein
aggregation in neurodegenerative diseases. Here, we show that N-oleoyl-dopamine
and N-arachidonyl-dopamine, which are endogenous brain substances and belong to
the N-acyldopamine (AcylDA) family, generate cellular inclusions through
aggresome formation without proteasome inhibition. Although AcylDA itself does
not inhibit proteasome activity in vitro, it activates the rearrangement of
vimentin distribution to form a vimentin cage surrounding aggresomes and
sequesters ubiquitinated proteins in aggresomes. The gene transcription of
p62/SQSTM1 was significantly increased by AcylDAs, whereas the transcription of
other ubiquitin-dependent autophagy receptors was unaffected. Genetic depletion
of p62 resulted in the loss of ubiquitinated-protein sequestration in aggresomes,
indicating that p62 is a critical component of aggresomes. Furthermore, AcylDAs
accelerate the aggregation of mutant huntingtin exon 1 proteins. These results
suggest that aggresome formation does not require proteasome dysfunction and
AcylDA-induced aggresome formation may participate in forming cytoplasmic protein
inclusions.
PMID- 29941920
TI - Long-range symmetry breaking in embedded ferroelectrics.
AB - The characteristic functionality of ferroelectric materials is due to the
symmetry of their crystalline structure. As such, ferroelectrics lend themselves
to design approaches that manipulate this structural symmetry by introducing
extrinsic strain. Using in situ dark-field X-ray microscopy to map lattice
distortions around deeply embedded domain walls and grain boundaries in BaTiO3,
we reveal that symmetry-breaking strain fields extend up to several micrometres
from domain walls. As this exceeds the average domain width, no part of the
material is elastically relaxed, and symmetry is universally broken. Such
extrinsic strains are pivotal in defining the local properties and self
organization of embedded domain walls, and must be accounted for by emerging
computational approaches to material design.
PMID- 29941921
TI - Seeing the forest and the trees.
PMID- 29941923
TI - Target tracking and 3D trajectory acquisition of cabbage butterfly (P. rapae)
based on the KCF-BS algorithm.
AB - Insect behaviour is an important research topic in plant protection. To study
insect behaviour accurately, it is necessary to observe and record their flight
trajectory quantitatively and precisely in three dimensions (3D). The goal of
this research was to analyse frames extracted from videos using Kernelized
Correlation Filters (KCF) and Background Subtraction (BS) (KCF-BS) to plot the 3D
trajectory of cabbage butterfly (P. rapae). Considering the experimental
environment with a wind tunnel, a quadrature binocular vision insect video
capture system was designed and applied in this study. The KCF-BS algorithm was
used to track the butterfly in video frames and obtain coordinates of the target
centroid in two videos. Finally the 3D trajectory was calculated according to the
matching relationship in the corresponding frames of two angles in the video. To
verify the validity of the KCF-BS algorithm, Compressive Tracking (CT) and Spatio
Temporal Context Learning (STC) algorithms were performed. The results revealed
that the KCF-BS tracking algorithm performed more favourably than CT and STC in
terms of accuracy and robustness.
PMID- 29941922
TI - The relation of local order to material properties in relaxor ferroelectrics.
AB - Correlating electromechanical and dielectric properties with nanometre-scale
order is the defining challenge for the development of piezoelectric oxides.
Current lead (Pb)-based relaxor ferroelectrics can serve as model systems with
which to unravel these correlations, but the nature of the local order and its
relation to material properties remains controversial. Here we employ recent
advances in diffuse scattering instrumentation to investigate crystals that span
the phase diagram of PbMg1/3Nb2/3O3-xPbTiO3 (PMN-xPT) and identify four forms of
local order. From the compositional dependence, we resolve the coupling of each
form to the dielectric and electromechanical properties observed. We show that
relaxor behaviour does not correlate simply with ferroic diffuse scattering;
instead, it results from a competition between local antiferroelectric
correlations, seeded by chemical short-range order, and local ferroic order. The
ferroic diffuse scattering is strongest where piezoelectricity is maximal and
displays previously unrecognized modulations caused by anion displacements. Our
observations provide new guidelines for evaluating displacive models and hence
the piezoelectric properties of environmentally friendly next-generation
materials.
PMID- 29941924
TI - First report on the application of near-infrared spectroscopy to predict the age
of Aedes albopictus Skuse.
AB - To date, no methodology has been described for predicting the age of Aedes
albopictus Skuse mosquitoes, commonly known as Asian tiger mosquitoes. In this
study, we report the potential of near-infrared spectroscopy (NIRS) technique for
characterizing the age of female laboratory reared Ae. albopictus. Using leave
one-out cross-validation analysis on a training set, laboratory reared mosquitoes
preserved in RNAlater for up to a month were assessed at 1, 3, 7, 9, 13, 16, 20
and 25 days post emergence. Mosquitoes (N = 322) were differentiated into two age
classes (< or >= 7 days) with 93% accuracy, into three age classes (<7, 7-13 and
>13 days old) with 76% accuracy, and on a continuous age scale to within +/-3
days of their actual average age. Similarly, models predicted mosquitoes (N =
146) excluded from the training model with 94% and 71% accuracy to the two and
the three age groups, respectively. We show for the first time that NIRS, with an
improved spectrometer and fibre configuration, can be used to predict the age of
laboratory reared female Ae. albopictus. Characterization of the age of Ae.
albopictus populations is crucial for determining the efficacy of vector control
interventions that target their survival.
PMID- 29941925
TI - The non-cylindrical crustal architecture of the Pyrenees.
AB - We exploit the data from five seismic transects deployed across the Pyrenees to
characterize the deep architecture of this collisional orogen. We map the main
seismic interfaces beneath each transect by depth migration of P-to-S converted
phases. The migrated sections, combined with the results of recent tomographic
studies and with maps of Bouguer and isostatic anomalies, provide a coherent
crustal-scale picture of the belt. In the Western Pyrenees, beneath the North
Pyrenean Zone, a continuous band of high density/velocity material is found at a
very shallow level (~10 km) beneath the Mauleon basin and near Saint-Gaudens. In
the Western Pyrenees, we also find evidence for northward continental subduction
of Iberian crust, down to 50-70 km depth. In the Eastern Pyrenees, these main
structural features are not observed. The boundary between these two domains is
near longitude 1.3 degrees E, where geological field studies document a major
change in the structure of the Cretaceous rift system, and possibly a shift of
its polarity, suggesting that the deep orogenic architecture of the Pyrenees is
largely controlled by structural inheritance.
PMID- 29941926
TI - Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis.
PMID- 29941927
TI - Influence of the 2-methylimidazole/zinc nitrate hexahydrate molar ratio on the
synthesis of zeolitic imidazolate framework-8 crystals at room temperature.
AB - The effect of the 2-methylimidazole (Hmim)/zinc nitrate hexahydrate (Zn) molar
ratio on the physicochemical characteristics of the zeolitic imidazolate
framework-8 (ZIF-8) was investigated. ZIF-8 crystals were synthesized by mixing
Hmim with Zn at room temperature without any additives in methanol solution. It
was found that Hmim/Zn molar ratio had significant influence on the
crystallinity, yield, particle size and porosity of ZIF-8. The samples
synthesized at low Hmim/Zn molar ratio showed a cubic shape, whereas at higher
Hmim/Zn ratios truncated rhombic dodecahedron or rhombic dodecahedron
morphologies were obtained. The particle size is decreased upon increasing the
Hmim/Zn molar ratio. Besides, higher Hmim/Zn molar ratio in a certain range
resulted in improving crystallinity, yield, surface area and micropore volume of
ZIF-8. The ZIF-8 crystals produced at Hmim/Zn molar ratio of 8 exhibited the best
characteristics. The present work provides new insights in relation to the role
of Hmim/Zn molar ratio on the synthesis process of ZIF-8.
PMID- 29941928
TI - GNAS shifts metabolism in pancreatic cancer.
PMID- 29941930
TI - Senescence-associated ribosome biogenesis defects contributes to cell cycle
arrest through the Rb pathway.
AB - Cellular senescence is a tumour suppressor programme characterized by a stable
cell cycle arrest. Here we report that cellular senescence triggered by a variety
of stimuli leads to diminished ribosome biogenesis and the accumulation of both
rRNA precursors and ribosomal proteins. These defects were associated with
reduced expression of several ribosome biogenesis factors, the knockdown of which
was also sufficient to induce senescence. Genetic analysis revealed that Rb but
not p53 was required for the senescence response to altered ribosome biogenesis.
Mechanistically, the ribosomal protein S14 (RPS14 or uS11) accumulates in the
soluble non-ribosomal fraction of senescent cells, where it binds and inhibits
CDK4 (cyclin-dependent kinase 4). Overexpression of RPS14 is sufficient to
inhibit Rb phosphorylation, inducing cell cycle arrest and senescence. Here we
describe a mechanism for maintaining the senescent cell cycle arrest that may be
relevant for cancer therapy, as well as biomarkers to identify senescent cells.
PMID- 29941929
TI - Mutant GNAS drives pancreatic tumourigenesis by inducing PKA-mediated SIK
suppression and reprogramming lipid metabolism.
AB - G protein alphas (GNAS) mediates receptor-stimulated cAMP signalling, which
integrates diverse environmental cues with intracellular responses. GNAS is
mutationally activated in multiple tumour types, although its oncogenic
mechanisms remain elusive. We explored this question in pancreatic tumourigenesis
where concurrent GNAS and KRAS mutations characterize pancreatic ductal
adenocarcinomas (PDAs) arising from intraductal papillary mucinous neoplasms
(IPMNs). By developing genetically engineered mouse models, we show that
GnasR201C cooperates with KrasG12D to promote initiation of IPMN, which progress
to invasive PDA following Tp53 loss. Mutant Gnas remains critical for tumour
maintenance in vivo. This is driven by protein-kinase-A-mediated suppression of
salt-inducible kinases (Sik1-3), associated with induction of lipid remodelling
and fatty acid oxidation. Comparison of Kras-mutant pancreatic cancer cells with
and without Gnas mutations reveals striking differences in the functions of this
network. Thus, we uncover Gnas-driven oncogenic mechanisms, identify Siks as
potent tumour suppressors, and demonstrate unanticipated metabolic heterogeneity
among Kras-mutant pancreatic neoplasms.
PMID- 29941932
TI - Grasping for aspartate in tumour metabolism.
PMID- 29941931
TI - Aspartate is an endogenous metabolic limitation for tumour growth.
AB - Defining the metabolic limitations of tumour growth will help to develop cancer
therapies1. Cancer cells proliferate slower in tumours than in standard culture
conditions, indicating that a metabolic limitation may restrict cell
proliferation in vivo. Aspartate synthesis can limit cancer cell proliferation
when respiration is impaired2-4; however, whether acquiring aspartate is
endogenously limiting for tumour growth is unknown. We confirm that aspartate has
poor cell permeability, which prevents environmental acquisition, whereas the
related amino acid asparagine is available to cells in tumours, but cancer cells
lack asparaginase activity to convert asparagine to aspartate. Heterologous
expression of guinea pig asparaginase 1 (gpASNase1), an enzyme that produces
aspartate from asparagine5, confers the ability to use asparagine to supply
intracellular aspartate to cancer cells in vivo. Tumours expressing gpASNase1
grow at a faster rate, indicating that aspartate acquisition is an endogenous
metabolic limitation for the growth of some tumours. Tumours expressing gpASNase1
are also refractory to the growth suppressive effects of metformin, suggesting
that metformin inhibits tumour growth by depleting aspartate. These findings
suggest that therapeutic aspartate suppression could be effective to treat
cancer.
PMID- 29941935
TI - Continuing Medical Education Questions: June 2018.
PMID- 29941933
TI - Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia
and in tumours.
AB - As oxygen is essential for many metabolic pathways, tumour hypoxia may impair
cancer cell proliferation1-4. However, the limiting metabolites for proliferation
under hypoxia and in tumours are unknown. Here, we assessed proliferation of a
collection of cancer cells following inhibition of the mitochondrial electron
transport chain (ETC), a major metabolic pathway requiring molecular oxygen5.
Sensitivity to ETC inhibition varied across cell lines, and subsequent
metabolomic analysis uncovered aspartate availability as a major determinant of
sensitivity. Cell lines least sensitive to ETC inhibition maintain aspartate
levels by importing it through an aspartate/glutamate transporter, SLC1A3.
Genetic or pharmacologic modulation of SLC1A3 activity markedly altered cancer
cell sensitivity to ETC inhibitors. Interestingly, aspartate levels also decrease
under low oxygen, and increasing aspartate import by SLC1A3 provides a
competitive advantage to cancer cells at low oxygen levels and in tumour
xenografts. Finally, aspartate levels in primary human tumours negatively
correlate with the expression of hypoxia markers, suggesting that tumour hypoxia
is sufficient to inhibit ETC and, consequently, aspartate synthesis in vivo.
Therefore, aspartate may be a limiting metabolite for tumour growth, and
aspartate availability could be targeted for cancer therapy.
PMID- 29941936
TI - Trans-Tracheal Cyanoacrylate Glue Injection for the Management of Malignant
Tracheoesophageal Fistula.
PMID- 29941937
TI - Continuing Medical Education Questions: June 2018.
PMID- 29941939
TI - High fidelity visualization of multiscale dynamics of laser-induced bubbles in
liquids containing gold nanoparticles.
AB - Cavitation in pure liquids and in liquids containing nanoparticles enables
applications in mechanics, bio-medicine, and energy. Its evolution carries a
significant interest. We describe the multiscale dynamic evolution of ultrafast
laser-induced cavitation in pure and gold-nanoparticles-doped liquids in one
dimensional geometries induced by non-diffractive ultrashort Bessel-Gauss laser
beams. Covering the complete electronic and thermomechanical cycle, from the
early plasma phase to bubble cavitation and collapse on ms timescales, we
reconstitute, using time-resolved imaging with amplitude and phase sensitivity,
the hydrodynamic phenomena concurring to bubble evolution. We indicate geometry
specific instabilities accompanying the collapse. The insertion of gold
nanoparticles of 200 nm size has subtle effects in the process energetics. Albeit
a moderate field enhancement minimizing the contribution to breakdown, the
nanoparticles play a role in the overall relaxation dynamics of bubbles. The
evolving bubble border in nanoparticles-containing liquids create a snow-plough
effect that sweeps the nanoparticles at the gas liquid interface. This indicates
that during the macroscopic cavity development, the nanoparticles were removed
from the interaction region and dragged by the hydrodynamic movement. We thus
shed light on the evolution of cavitation bubbles not triggered but perturbed by
the presence of nanoparticles.
PMID- 29941938
TI - NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus
placebo in young people at ultra-high risk of psychotic disorders-medium-term
follow-up and clinical course.
AB - This study reports a medium-term follow-up of a randomised, double-blind, placebo
controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk
for psychosis (UHR) patients. Primary outcomes of interest were transition to
psychosis and symptomatic and functional outcome. A secondary aim was to
investigate clinical predictors of medium-term outcome. Three hundred four UHR
participants were recruited across 10 specialised early psychosis services in
Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3
PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management
(CBCM), over the 6-month study period, with participants receiving further CBCM
sessions on basis of need between months 6-12. Mean time to follow-up was 3.4
(median = 3.3; SD = 0.9) years. There was a modest increase in transitions
between 12-month and medium-term follow-up (11-13%) and substantial improvement
in symptoms and functioning between baseline and follow-up, with no differences
between the treatment groups. Most improvement had been achieved by end of the
intervention. 55% of the sample received mental health treatment between end of
intervention and follow-up. Omega-3 PUFA did not provide additional benefits to
good quality psychosocial intervention over the medium term. Although most
improvement had been achieved by end of intervention the substantial rates of
post-intervention mental health service use indicate longer-term clinical need in
UHR patients. The post-intervention phase treatment or the longer-term effect of
CBCM, or a combination of the two, may have contributed to maintaining the gains
achieved during the intervention phase and prevented significant deterioration
after this time.
PMID- 29941940
TI - NLRP3 inflammasome is expressed and regulated in human islets.
AB - NRLP3 inflammasome is a protein complex involved in the maturation of IL1beta. In
the onset of type 1 diabetes as well as in islet transplantation, IL-1beta is one
of the cytokines involved in the recruitment of immune cells in islets and
eventually in islet destruction. Whether IL-1beta is produced by islet cells is
still under debate and NLRP3 inflammasome-dependent IL-1beta production has not
been yet determined in human islets. The aim of this study was to determine the
expression and the regulation of the NRLP3 inflammasome in human islets. Human
islets were stimulated with LPS and successively with ATP (LPS + ATP) in the
presence or absence of the inflammasome inhibitor glyburide. Islets were also
incubated in hypoxic or normoxic conditions for 24 h in the presence or absence
of glyburide. Then, IL1B and NLRP3 expression was studied by real time PCR,
protein expression by western blot, protein localization by immunofluorescence
and protein secretion by ELISA. LPS + ATP increased gene expression of NRLP3 and
IL1B. Glyburide partially prevented this effect. IL-1beta protein was localized
in beta and non-beta cells. Moreover, LPS + ATP increased IL-1beta protein
expression and production, which were prevented by glyburide. Hypoxia increased
gene expression of NRLP3 and IL1B and induced IL-1beta and caspase-1 production.
Finally, hypoxia-induced cell death which was not prevented by inhibition of
NLRP3 inflammasome. NRLP3 inflammasome is expressed and plays a role in IL-1beta
production by human islets. By contrast, NRLP3 inflammasome activation is not
involved in islet cell death induced by hypoxia.
PMID- 29941941
TI - Insight into the characteristics, removal, and toxicity of effluent organic
matter from a pharmaceutical wastewater treatment plant during catalytic
ozonation.
AB - Changes in the characteristics, removal efficiency, and toxicity of
pharmaceutical effluent organic matter (EfOM) after catalytic ozonation were
investigated in this study. After a 90-min treatment with a catalytic ozonation
process (COP) in the presence of MnO2 ceramsite, the total organic carbon (TOC),
UV254, colority, protein, and humic acid removal rates were 13.24%, 60.83%,
85.42%, 29.36% and 74.19%, respectively. The polysaccharide content increased by
12.73 mg/L during the COP for reaction times between 0 and ~50 min and decreased
by 6.97 mg/L between 50 and ~90 min. Furthermore, 64.44% of the total colority
was detected in the hydrophobic organic matter (HOM) fraction, and after the COP,
and 88.69% of the colority in the HOM was eliminated. Meanwhile, only 59.18% of
the colority in the hydrophilic organic matter (HIM) fraction was removed. GC-MS
analysis showed that 38 organic pollutant species were completely removed, 8 were
partially removed, and 7 were generated. After 90 min of COP treatment, the
pharmaceutical EfOM toxicity was effectively reduced based on the higher
incubation and lower mortality rates.
PMID- 29941942
TI - Molecular diversity of clustered protocadherin-alpha required for sensory
integration and short-term memory in mice.
AB - Clustered protocadherins (Pcdhs) are neuronal cell adhesion molecules
characterized by homophilic adhesion between the tetramers of 58 distinct
isoforms in mice. The diversity of Pcdhs and resulting highly-specific neuronal
adhesion may be required for the formation of neural circuits for executing
higher brain functions. However, this hypothesis remains to be tested, because
knockout of Pcdh genes produces abnormalities that may interfere with higher
brain functions indirectly. In Pcdh-alpha1,12 mice, only alpha1, alpha12 and two
constitutive isoforms are expressed out of 14 isoforms. The appearance and
behavior of Pcdh-alpha1,12 mice are similar to those of wild-type mice, and most
abnormalities reported in Pcdh-alpha knockout mice are not present in Pcdh
alpha1,12 mice. We examined Pcdh-alpha1,12 mice in detail, and found that
cortical depression induced by sensory mismatches between vision and whisker
sensation in the visual cortex was impaired. Since Pcdh-alpha is densely
distributed over the cerebral cortex, various types of higher function are likely
impaired in Pcdh-alpha1,12 mice. As expected, visual short-term memory of
space/shape was impaired in behavioral experiments using space/shape cues.
Furthermore, behavioral learning based on audio-visual associative memory was
also impaired. These results indicate that the molecular diversity of Pcdh-alpha
plays essential roles for sensory integration and short-term memory.
PMID- 29941943
TI - Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that
regulate lineage specification.
AB - MicroRNAs (miRNAs) are known to be crucial players in governing the
differentiation of human induced pluripotent stem cells (hiPSCs). Despite their
utter importance, identifying key lineage specifiers among the myriads of
expressed miRNAs remains challenging. We believe that the current practice in
mining miRNA specifiers via delineating dynamic fold-changes only is inadequate.
Our study, therefore, provides evidence to pronounce "lineage specificity" as
another important attribute to qualify for these lineage specifiers. Adopted
hiPSCs were differentiated into representative lineages (hepatic, nephric and
neuronal) over all three germ layers whilst the depicted miRNA expression changes
compiled into an integrated atlas. We demonstrated inter-lineage analysis shall
aid in the identification of key miRNAs with lineage-specificity, while these
shortlisted candidates were collectively known as "lineage-specific miRNAs".
Subsequently, we followed through the fold-changes along differentiation via
computational analysis to identify miR-192 and miR-372-3p, respectively, as
representative candidate key miRNAs for the hepatic and nephric lineages. Indeed,
functional characterization validated that miR-192 and miR-372-3p regulate
lineage differentiation via modulation of the expressions of lineage-specific
genes. In summary, our presented miRNA atlas is a resourceful ore for the mining
of key miRNAs responsible for lineage specification.
PMID- 29941944
TI - Spatiotemporal endothelial cell - pericyte association in tumors as shown by high
resolution 4D intravital imaging.
AB - Endothelial cells and pericytes are integral cellular components of the
vasculature with distinct interactive functionalities. To study dynamic
interactions between these two cells we created two transgenic animal lines. A
truncated eNOS (endothelial nitric oxide synthase) construct was used as a GFP
tag for endothelial cell evaluation and an inducible Cre-lox recombination, under
control of the Pdgfrb (platelet derived growth factor receptor beta) promoter,
was created for pericyte assessment. Also, eNOStag-GFP animals were crossed with
the already established Cspg4-DsRed mice expressing DsRed fluorescent protein in
pericytes. For intravital imaging we used tumors implanted in the dorsal skinfold
of these transgenic animals. This setup allowed us to study time and space
dependent complexities, such as distribution, morphology, motility, and
association between both vascular cell types in all angiogenetic stages, without
the need for additional labeling. Moreover, as fluorescence was still clearly
detectable after fixation, it is possible to perform comparative histology
following intravital evaluation. These transgenic mouse lines form an excellent
model to capture collective and individual cellular and subcellular endothelial
cell - pericyte dynamics and will help answer key questions on the cellular and
molecular relationship between these two cells.
PMID- 29941945
TI - Nonstoichiometric titanium dioxide nanotubes with enhanced catalytical activity
under visible light.
AB - The catalytic activity of nanotubular titanium dioxide films formed during the
oxidation of acetone to carbon dioxide under the action of visible light with a
wavelength of 450 nm was found to be approximately 2 times higher compared to
standard titanium dioxide (Degussa P25). The nanotubular films were grown by the
anodization of titanium foil using an original technique. Diffuse reflectance
spectra of the films are attributed to enhanced activity in the visible spectrum
by the nonstoichiometry of titanium dioxide near the interface between the
nanotubular film and the titanium foil substrate.
PMID- 29941947
TI - Needle beats pill in gestational diabetes mellitus.
PMID- 29941948
TI - Mechanics-guided developmental fate patterning.
PMID- 29941946
TI - NCX1 and NCX3 as potential factors contributing to neurodegeneration and
neuroinflammation in the A53T transgenic mouse model of Parkinson's Disease.
AB - Na+-Ca2+ exchanger (NCX) isoforms constitute the major cellular Ca2+ extruding
system in neurons and microglia. We herein investigated the role of NCX isoforms
in the pathophysiology of Parkinson's disease (PD). Their expression and activity
were evaluated in neurons and glia of mice expressing the human A53T variant of
alpha-synuclein (A53T mice), an animal model mimicking a familial form of PD.
Western blotting revealed that NCX3 expression in the midbrain of 12-month old
A53T mice was lower than that of wild type (WT). Conversely, NCX1 expression
increased in the striatum. Immunohistochemical studies showed that glial
fibrillary acidic protein (GFAP)-positive astroglial cells significantly
increased in the substantia nigra pars compacta (SNc) and in the striatum.
However, the number and the density of tyrosine hydroxylase (TH)-positive neurons
decreased in both brain regions. Interestingly, ionized calcium binding adaptor
molecule 1 (IBA-1)-positive microglial cells increased only in the striatum of
A53T mice compared to WT. Double immunostaining studies showed that in A53T mice,
NCX1 was exclusively co-expressed in IBA-1-positive microglial cells in the
striatum, whereas NCX3 was solely co-expressed in TH-positive neurons in SNc.
Beam walking and pole tests revealed a reduction in motor performance for A53T
mice compared to WT. In vitro experiments in midbrain neurons from A53T and WT
mice demonstrated a reduction in NCX3 expression, which was accompanied by
mitochondrial overload of Ca2+ ions, monitored with confocal microscopy by X-Rhod
1 fluorescent dye. Collectively, in vivo and in vitro findings suggest that the
reduction in NCX3 expression and activity in A53T neurons from midbrain may cause
mitochondrial dysfunction and neuronal death in this brain area, whereas NCX1
overexpression in microglial cells may promote their proliferation in the
striatum.
PMID- 29941949
TI - Biomaterials driving repair after stroke.
PMID- 29941950
TI - Pure spin currents find the off switch.
PMID- 29941951
TI - Out of step with time.
PMID- 29941952
TI - Hydrogen to the rescue.
PMID- 29941953
TI - NS-018 reduces myeloma cell proliferation and suppresses osteolysis through
inhibition of the JAK2 and Src signaling pathways.
PMID- 29941954
TI - Temperature-dependent virus lifecycle choices may reveal and predict facets of
the biology of opportunistic pathogenic bacteria.
AB - Melioidosis, a serious illness caused by Burkholderia pseudomallei, results in up
to 40% fatality in infected patients. The pathogen is found in tropical water and
soil. Recent findings demonstrated that bacterial numbers can be regulated by a
novel clade of phages that are abundant in soil and water. These phages
differentially infect their bacterial hosts causing lysis at high temperatures
and lysogeny at lower temperatures. Thus seasonal and daily temperature
variations would cause switches in phage-bacteria interactions. We developed
mathematical models using realistic parameters to explore the impact of phages on
B. pseudomallei populations in the surface water of rice fields over time and
under seasonally changing environmental conditions. Historical records were used
to provide UV radiation levels and temperature for two Thailand provinces. The
models predict seasonal variation of phage-free bacterial numbers correlates with
the higher risk of melioidosis acquisition during the "warm and wet" season. We
find that enrichment of the environment may lead to irregular large amplitude
pulses of bacterial numbers that could significantly increase the probability of
disease acquisition. Our results suggest that the phages may regulate B.
pseudomallei populations throughout the seasons, and these data can potentially
help improve the melioidosis prevention efforts in Southeast Asia.
PMID- 29941955
TI - Elucidating the hypoxic stress response in barley (Hordeum vulgare L.) during
waterlogging: A proteomics approach.
AB - Waterlogging is one of the major abiotic stresses that affects barley production
and yield quality. Proteomics techniques have been widely utilized to explore the
mechanisms involved in the responses to abiotic stress. In this study, two barley
genotypes with contrasting responses to waterlogging stress were analyzed with
proteomic technology. The waterlogging treatment caused a greater reduction in
biomass and photosynthetic performance in the waterlogging-sensitive genotype
TF57 than that in the waterlogging-tolerant genotype TF58. Under waterlogging
stress, 30, 30, 20 and 20 differentially expressed proteins were identified
through tandem mass spectrometry analysis in the leaves, adventitious roots,
nodal roots and seminal roots, respectively. Among these proteins, photosynthesis
, metabolism- and energy-related proteins were differentially expressed in the
leaves, with oxygen-evolving enhancer protein 1, ATP synthase subunit and heat
shock protein 70 being up-regulated in TF58. Pyruvate decarboxylase (PDC), 1
amino cyclopropane 1-carboxylic acid oxidase (ACO), glutamine synthetase (GS),
glutathione S-transferases (GST) and beta-1, 3-glucanase in adventitious, nodal
and seminal roots were more abundant in TF58 than those in TF57 under
waterlogging stress. Ten representative genes were selected for validation by qRT
PCR in different genotypes with known waterlogging tolerance, and the expression
levels of three candidate genes (PDC, ACO and GST) increased in the roots of all
genotypes in response to the waterlogging stress. These three genes might play a
significant role in the adaptation process of barley under waterlogging stress.
The current results partially determined the mechanisms of waterlogging tolerance
and provided valuable information for the breeding of barley with enhanced
tolerance to waterlogging.
PMID- 29941957
TI - Arousal dependent modulation of thalamo-cortical functional interaction.
AB - Ongoing changes in arousal influence sensory processing and behavioral
performance. Yet the circuit-level correlates for this influence remain poorly
understood. Here, we investigate how functional interaction between posterior
parietal cortex (PPC) and lateral posterior (LP)/Pulvinar is influenced by
ongoing fluctuations in pupil-linked arousal, which is a non-invasive measure of
neuromodulatory tone in the brain. We find that fluctuations in pupil-linked
arousal correlate with changes to PPC to LP/Pulvinar oscillatory interaction,
with cortical alpha oscillations driving activity during low arousal states, and
LP/Pulvinar driving PPC in the theta frequency band during higher arousal states.
Active visual exploration by saccadic eye movements elicits similar transitions
in thalamo-cortical interaction. Furthermore, the presentation of naturalistic
video stimuli induces thalamo-cortical network states closely resembling epochs
of high arousal in the absence of visual input. Thus, neuromodulators may play a
role in dynamically sculpting the patterns of thalamo-cortical functional
interaction that underlie visual processing.
PMID- 29941958
TI - Descending neurons from the lateral accessory lobe and posterior slope in the
brain of the silkmoth Bombyx mori.
AB - A population of descending neurons connect the brain and thoracic motor center,
playing a critical role in controlling behavior. We examined the anatomical
organization of descending neurons (DNs) in the brain of the silkmoth Bombyx
mori. Moth pheromone orientation is a good model to investigate neuronal
mechanisms of behavior. Based on mass staining and single-cell staining, we
evaluated the anatomical organization of neurite distribution by DNs in the
brain. Dense innervation was observed in the posterior-ventral part of the brain
called the posterior slope (PS). We analyzed the morphology of DNs innervating
the lateral accessory lobe (LAL), which is considered important for moth
olfactory behavior. We observed that all LAL DNs also innervate the PS,
suggesting the integration of signals from the LAL and PS. We also identified a
set of DNs innervating the PS but not the LAL. These DNs were sensitive to the
sex pheromone, suggesting a role of the PS in motor control for pheromone
processing. Here we discuss the organization of descending pathways for pheromone
orientation.
PMID- 29941956
TI - Transcriptome analysis of two contrasting rice cultivars during alkaline stress.
AB - Soil alkalinity greatly affects plant growth and crop productivity. Although RNA
Seq analyses have been conducted to investigate genome-wide gene expression in
response to alkaline stress in many plants, the expressions of alkali-responsive
genes in rice have not been previously investigated. In this study, the
transcriptomic data between an alkaline-tolerant (WD20342) and an alkaline
sensitive (Caidao) rice cultivar were compared under alkaline stress conditions.
A total of 962 important alkali-responsive (IAR) genes from highly differentially
expressed genes (DEGs) were identified, including 28 alkaline-resistant cultivar
related genes, 771 alkaline-sensitive cultivar-related genes and 163 cultivar-non
specific genes. Gene ontology (GO) analysis indicated the enrichment of IAR genes
involved in various stimulus or stress responses. According to Kyoto Encyclopedia
of Genes and Genomes (KEGG) pathway analysis, the IAR genes were related
primarily to plant hormone signal transduction and biosynthesis of secondary
metabolites. Additionally, among these 962 IAR genes, 74 were transcription
factors and 15 occurred with differential alternative splicing between the
different samples after alkaline treatment. Our results provide a valuable
resource on alkali-responsive genes and should benefit the improvement of
alkaline stress tolerance in rice.
PMID- 29941959
TI - Angular- and Polarization-insensitive Ultrathin Double-layered Metamaterial
Absorber for Ultra-wideband Application.
AB - We proposed an ultra-thin polarization-insensitive metamaterial absorber (MMA)
for ultra-wideband and wide incident angle operation. The MMA is composed of
double-layer symmetric split rings (SSRs) connected with two orthogonally
arranged bars and the ground metallic plane separated by two identical
substrates. Multiple metallic layers and scalabilities are employed to provide
broadband absorptivity based on the cooperated mechanisms of the Ohmic loss and
the Fabry-Perot interference. To further broaden the absorption bandwidth, four
lumped resistors are loaded with the SSRs on the top metallic layer. By this
means, an ultra-wideband absorbance is achieved nearly in 4~22 GHz, two gentle
slope belts with absorptivity over 60% and 80% in 4~12 GHz and 12~22 GHz,
respectively. The whole structure is with an ultrathin thickness of 2.4 mm, which
is 0.032lambdalow and 0.176lambdahigh corresponds to the lowest and highest
absorption frequency separately. Meanwhile, the symmetric structure enables the
MMA of satisfactory stability for polarization and wide incident angles.
Numerical and experimental results prove the capability of the proposed MMA for
ultra-wideband absorbance.
PMID- 29941960
TI - CD4+CD28null T Lymphocytes are Associated with the Development of Atrial
Fibrillation after Elective Cardiac Surgery.
AB - Post-operative atrial fibrillation (POAF) is postulated as a complex interaction
of different pathogenic factors, suggesting inflammatory processes as a main
trigger of this particular type of atrial fibrillation. Therefore, the study
sought to assess the impact of cellular immunity on the development of POAF.
Comparing patients developing POAF to individuals free of POAF the fraction of
CD4+CD28null T Lymphocytes was significantly higher in individuals developing
POAF (11.1% [POAF] vs. 1.9% [non-POAF]; p < 0.001). CD4+CD28null cells were
independently associated with the development of POAF with an adjusted odds ratio
per one standard deviation of 4.89 (95% CI: 2.68-8.97; p < 0.001). Compared to N
terminal Pro-Brain Natriuretic Peptide, the fraction of CD4+CD28null cells
demonstrated an increased discriminatory power for the development of POAF (NRI:
87.9%, p < 0.001; IDI: 30.9%, p < 0.001). Interestingly, a pre-operative statin
therapy was associated with a lower fraction of CD4+CD28null cells (p < 0.001)
and showed an inverse association with POAF (p < 0.001). CD4+CD28null cells
proved to be predictive for the development of POAF after cardiac surgery. Our
results potentially indicate an auto-immune impact of this preexisting, highly
cytotoxic T cell subset in the pathogenesis of POAF, which might be modified via
the anti-inflammatory potential of a pre-operative statin-therapy.
PMID- 29941962
TI - Distinct macrophage subsets in the human heart.
PMID- 29941961
TI - Simultaneous and stoichiometric purification of hundreds of oligonucleotides.
AB - Purification of oligonucleotides has traditionally relied on mobility-based
separation methods. However, these are imperfect, biased, and difficult to scale
high multiplex. Here, we present a method for simultaneous purification of many
oligonucleotides that also normalizes concentrations. The method uses a
rationally designed randomer capture probe to enrich for oligos with perfect 5'
sequences, based on the observation that synthesis errors are correlated: product
molecules with one or more deletions in one region are also more likely to have
deletions in other regions. Next-generation sequencing analysis of 64-plex 70 nt
purification products show a median 78% purity, a significant improvement over
polyacrylamide gel electrophoresis and high pressure liquid chromatography (60%
median purity). Additionally, 89% of the oligo products are within a factor of 2
of the median concentration.
PMID- 29941963
TI - LIMA1 variant influences cholesterol absorption.
PMID- 29941964
TI - Erectile dysfunction predicts CVD events.
PMID- 29941965
TI - Early Neolithic executions indicated by clustered cranial trauma in the mass
grave of Halberstadt.
AB - The later phase of the Central European Early Neolithic witnessed a rise in
collective lethal violence to a level undocumented up to this date. This is
evidenced by repeated massacres of settled communities of the Linearbandkeramik
(ca. 5600-4900 cal BC), the first full farming culture in this area. Skeletal
remains of several dozen victims of this prehistoric warfare are known from
different sites in Germany and Austria. Here we show that the mass grave of
Halberstadt, Germany, a new mass fatality site from the same period, reveals
further and so far unknown facets of Early Neolithic collective lethal violence.
A highly selected, almost exclusively adult male and non-local population sample
was killed by targeted blows to the back of the head, indicating a practice of
systematic execution under largely controlled conditions followed by careless
disposal of the bodies. This discovery significantly increases current knowledge
about warfare-related violent behaviour in Early Neolithic Central Europe.
PMID- 29941966
TI - Transcriptional analysis of adipose tissue during development reveals depot
specific responsiveness to maternal dietary supplementation.
AB - Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident
with the loss of the BAT-specific uncoupling protein (UCP)1 and rapid fat growth.
The extent to which this adaptation may vary between anatomical locations remains
unknown, or whether the process is sensitive to maternal dietary supplementation.
We, therefore, conducted a data mining based study on the major fat depots (i.e.
epicardial, perirenal, sternal (which possess UCP1 at 7 days), subcutaneous and
omental) (that do not possess UCP1) of young sheep during the first month of
life. Initially we determined what effect adding 3% canola oil to the maternal
diet has on mitochondrial protein abundance in those depots which possessed UCP1.
This demonstrated that maternal dietary supplementation delayed the loss of
mitochondrial proteins, with the amount of cytochrome C actually being increased.
Using machine learning algorithms followed by weighted gene co-expression network
analysis, we demonstrated that each depot could be segregated into a unique and
concise set of modules containing co-expressed genes involved in adipose
function. Finally using lipidomic analysis following the maternal dietary
intervention, we confirmed the perirenal depot to be most responsive. These
insights point at new research avenues for examining interventions to modulate
fat development in early life.
PMID- 29941967
TI - Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor
neurons from the SMNDelta7 mouse model of SMA.
AB - Spinal muscular atrophy (SMA) is a severe motor neuron (MN) disease caused by the
deletion or mutation of the survival motor neuron 1 (SMN1) gene, which results in
reduced levels of the SMN protein and the selective degeneration of lower MNs.
The best-known function of SMN is the biogenesis of spliceosomal snRNPs, the
major components of the pre-mRNA splicing machinery. Therefore, SMN deficiency in
SMA leads to widespread splicing abnormalities. We used the SMN?7 mouse model of
SMA to investigate the cellular reorganization of polyadenylated mRNAs associated
with the splicing dysfunction in MNs. We demonstrate that SMN deficiency induced
the abnormal nuclear accumulation in euchromatin domains of poly(A) RNA granules
(PARGs) enriched in the splicing regulator Sam68. However, these granules lacked
other RNA-binding proteins, such as TDP43, PABPN1, hnRNPA12B, REF and Y14, which
are essential for mRNA processing and nuclear export. These effects were
accompanied by changes in the alternative splicing of the Sam68-dependent Bcl-x
and Nrnx1 genes, as well as changes in the relative accumulation of the intron
containing Chat, Chodl, Myh9 and Myh14 mRNAs, which are all important for MN
functions. PARG-containing MNs were observed at presymptomatic SMA stage,
increasing their number during the symptomatic stage. Moreover, the massive
accumulations of poly(A) RNA granules in MNs was accompanied by the cytoplasmic
depletion of polyadenylated mRNAs for their translation. We suggest that the SMN
dependent abnormal accumulation of polyadenylated mRNAs and Sam68 in PARGs
reflects a severe dysfunction of both mRNA processing and translation, which
could contribute to SMA pathogenesis.
PMID- 29941968
TI - Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in
complex with ssDNA.
AB - The human APOBEC3G protein is a cytidine deaminase that generates cytidine to
deoxy-uridine mutations in single-stranded DNA (ssDNA), and capable of
restricting replication of HIV-1 by generating mutations in viral genome. The
mechanism by which APOBEC3G specifically deaminates 5'-CC motifs has remained
elusive since structural studies have been hampered due to apparently weak ssDNA
binding of the catalytic domain of APOBEC3G. We overcame the problem by
generating a highly active variant with higher ssDNA affinity. Here, we present
the crystal structure of this variant complexed with a ssDNA substrate at 1.86 A
resolution. This structure reveals atomic-level interactions by which APOBEC3G
recognizes a functionally-relevant 5'-TCCCA sequence. This complex also reveals a
key role of W211 in substrate recognition, implicating a similar recognition in
activation-induced cytidine deaminase (AID) with a conserved tryptophan.
PMID- 29941969
TI - Spontaneous buckling of contractile poroelastic actomyosin sheets.
AB - Shape transitions in developing organisms can be driven by active stresses,
notably, active contractility generated by myosin motors. The mechanisms
generating tissue folding are typically studied in epithelia. There, the
interaction between cells is also coupled to an elastic substrate, presenting a
major difficulty for studying contraction induced folding. Here we study the
contraction and buckling of active, initially homogeneous, thin elastic
actomyosin networks isolated from bounding surfaces. The network behaves as a
poroelastic material, where a flow of fluid is generated during contraction.
Contraction starts at the system boundaries, proceeds into the bulk, and
eventually leads to spontaneous buckling of the sheet at the periphery. The
buckling instability resulted from system self-organization and from the
spontaneous emergence of density gradients driven by the active contractility.
The buckling wavelength increases linearly with sheet thickness. Our system
offers a well-controlled way to study mechanically induced, spontaneous shape
transitions in active matter.
PMID- 29941970
TI - Evidence for neurogenesis in the medial cortex of the leopard gecko, Eublepharis
macularius.
AB - Although lizards are often described as having robust neurogenic abilities, only
a handful of the more than 6300 species have been explored. Here, we provide the
first evidence of homeostatic neurogenesis in the leopard gecko (Eublepharis
macularius). We focused our study on the medial cortex, homologue of the
mammalian hippocampal formation. Using immunostaining, we identified
proliferating pools of neural stem/progenitor cells within the sulcus
septomedialis, the pseudostratified ventricular zone adjacent to the medial
cortex. Consistent with their identification as radial glia, these cells
expressed SOX2, glial fibrillary acidic protein, and Vimentin, and demonstrated a
radial morphology. Using a 5-bromo-2'-deoxyuridine cell tracking strategy, we
determined that neuroblast migration from the ventricular zone to the medial
cortex takes ~30-days, and that newly generated neuronal cells survived for at
least 140-days. We also found that cell proliferation within the medial cortex
was not significantly altered following rupture of the tail spinal cord (as a
result of the naturally evolved process of caudal autotomy). We conclude that the
sulcus septomedialis of the leopard gecko demonstrates all the hallmarks of a
neurogenic niche.
PMID- 29941971
TI - Learning and Memory Impairments in Patients with Minimal Hepatic Encephalopathy
are Associated with Structural and Functional Connectivity Alterations in
Hippocampus.
AB - Patients with minimal hepatic encephalopathy (MHE) show mild cognitive impairment
associated with alterations in attentional and executive networks. There are no
studies evaluating the relationship between memory in MHE and structural and
functional connectivity (FC) changes in the hippocampal system. This study aimed
to evaluate verbal learning and long-term memory in cirrhotic patients with (C
MHE) and without MHE (C-NMHE) and healthy controls. We assessed the relationship
between alterations in memory and the structural integrity and FC of the
hippocampal system. C-MHE patients showed impairments in learning, long-term
memory, and recognition, compared to C-NMHE patients and controls. Cirrhotic
patients showed reduced fimbria volume compared to controls. Larger volumes in
hippocampus subfields were related to better memory performance in C-NMHE
patients and controls. C-MHE patients presented lower FC between the L
presubiculum and L-precuneus than C-NMHE patients. Compared to controls, C-MHE
patients had reduced FC between L-presubiculum and subiculum seeds and bilateral
precuneus, which correlated with cognitive impairment and memory performance.
Alterations in the FC of the hippocampal system could contribute to learning and
long-term memory impairments in C-MHE patients. This study demonstrates the
association between alterations in learning and long-term memory and structural
and FC disturbances in hippocampal structures in cirrhotic patients.
PMID- 29941973
TI - Materials informatics for self-assembly of functionalized organic precursors on
metal surfaces.
AB - Bottom-up fabrication via on-surface molecular self-assembly is a way to create
defect-free, low-dimensional nanomaterials. For bottom-up fabrication to succeed,
precursor molecules which correctly assemble into the target structure must be
first identified. Here we present an informatics technique which connects self
assembled structures with particular chemical properties of the precursor
molecules. Application of this method produces a visual output (a dendrogram)
that functions much like the periodic table, but whereas the periodic table puts
atoms into categories according to the way in which they bond to each other, the
dendrogram put molecules into categories according to the way in which they
arrange in a self-assembled structure. By applying this method to the case of
functionalized bianthracene precursors adsorbed to copper(111), we identify the
functional groups needed to assemble one-dimensional chains, two-dimensional
tilings, and other shapes. This methodology can therefore help to identify
appropriate precursor molecules for forming target nanomaterials via bottom-up
fabrication.
PMID- 29941972
TI - Omics approaches revealed how arbuscular mycorrhizal symbiosis enhances yield and
resistance to leaf pathogen in wheat.
AB - Besides improved mineral nutrition, plants colonised by arbuscular mycorrhizal
(AM) fungi often display increased biomass and higher tolerance to biotic and
abiotic stresses. Notwithstanding the global importance of wheat as an
agricultural crop, its response to AM symbiosis has been poorly investigated. We
focused on the role of an AM fungus on mineral nutrition of wheat, and on its
potential protective effect against Xanthomonas translucens. To address these
issues, phenotypical, molecular and metabolomic approaches were combined.
Morphological observations highlighted that AM wheat plants displayed an
increased biomass and grain yield, as well as a reduction in lesion area
following pathogen infection. To elucidate the molecular mechanisms underlying
the mycorrhizal phenotype, we investigated changes of transcripts and proteins in
roots and leaves during the double (wheat-AM fungus) and tripartite (wheat-AM
fungus-pathogen) interaction. Transcriptomic and proteomic profiling identified
the main pathways involved in enhancing plant biomass, mineral nutrition and in
promoting the bio-protective effect against the leaf pathogen. Mineral and amino
acid contents in roots, leaves and seeds, and protein oxidation profiles in
leaves, supported the omics data, providing new insight into the mechanisms
exerted by AM symbiosis to confer stronger productivity and enhanced resistance
to X. translucens in wheat.
PMID- 29941974
TI - Imaging through scattering media with the auxiliary of a known reference object.
AB - Imaging through scattering media has been one of the main challenges in optics,
and are encountered in many different disciplines of sciences, ranging from
biology, mesoscopic physics to astronomy. Recently, various methods have been
proposed. In this manuscript, we propose a robust method for imaging through
scattering media in a reflective geometry, a scenario widely encountered in non
invasive and marker-free biological imaging. The proposed method relies on the a
priori information of a known reference object in the neighborhood of the target,
and uses it as an auxiliary to reconstruct the target image. We show that the
target image can be analytically reconstructed from the autocorrelation of the
recorded speckle if the reference is point-like, otherwise, deconvolution with
the reference speckle should be performed. We experimentally demonstrate the
proposed method in a proof-of-concept system with an LED illumination through a
thick ground glass.
PMID- 29941976
TI - Physical Unclonable Function based on a Multi-Mode Optical Waveguide.
AB - Physical unclonable functions are the physical equivalent of one-way mathematical
transformations that, upon external excitation, can generate irreversible
responses. Exceeding their mathematical counterparts, their inherent physical
complexity renders them resilient to cloning and reverse engineering. When these
features are combined with their time-invariant and deterministic operation, the
necessity to store the responses (keys) in non-volatile means can be alleviated.
This pivotal feature, makes them critical components for a wide range of
cryptographic-authentication applications, where sensitive data storage is
restricted. In this work, a physical unclonable function based on a single
optical waveguide is experimentally and numerically validated. The system's
responses consist of speckle-like images that stem from mode-mixing and
scattering events of multiple guided transverse modes. The proposed configuration
enables the system's response to be simultaneously governed by multiple physical
scrambling mechanisms, thus offering a radical performance enhancement in terms
of physical unclonability compared to conventional optical implementations.
Additional features like physical re-configurability, render our scheme suitable
for demanding authentication applications.
PMID- 29941975
TI - Towards femtosecond on-chip electronics based on plasmonic hot electron nano
emitters.
AB - To combine the advantages of ultrafast femtosecond nano-optics with an on-chip
communication scheme, optical signals with a frequency of several hundreds of THz
need to be down-converted to coherent electronic signals propagating on-chip. So
far, this has not been achieved because of the overall slow response time of
nanoscale electronic circuits. Here, we demonstrate that 14 fs optical pulses in
the near-infrared can drive electronic on-chip circuits with a prospective
bandwidth up to 10 THz. The corresponding electronic pulses propagate in
macroscopic striplines on a millimeter scale. We exploit femtosecond
photoswitches based on asymmetric, nanoscale metal junctions to drive the pulses.
The non-linear ultrafast response is based on a plasmonically enhanced,
multiphoton absorption resulting in a field emission of ballistic hot electrons
propagating across the nanoscale junctions. Our results pave the way towards
femtosecond electronics integrated in wafer-scale THz circuits.
PMID- 29941978
TI - Peripubertal stress-induced heightened aggression: modulation of the
glucocorticoid receptor in the central amygdala and normalization by mifepristone
treatment.
AB - Despite the enormous negative impact of excessive aggression for individuals and
societies, there is a paucity of treatments. Here, using a peripubertal stress
model of heightened aggression in rats, we investigated the involvement of the
glucocorticoid system and tested the effectiveness of antiglucocorticoid
treatment to normalize behavior. We assessed peripubertal stress-induced changes
in glucocorticoid (GR) and mineralocorticoid (MR) gene expression in different
amygdala nuclei and hippocampus, and report a specific increase in GR mRNA
expression in the central amygdala (CeA). Administration of mifepristone (10
mg/kg), a GR antagonist, before stressor exposure at peripuberty prevented the
habituation of plasma corticosterone responses observed throughout the stress
protocol. This treatment also prevented the increase in aggression and GR
expression in the CeA observed in peripubertally stressed rats at adulthood.
Viral downregulation of CeA GR expression at adulthood led to reduced aggression.
Subsequently, we showed that a brief, 3-day, treatment with mifepristone at
adulthood was effective to normalize the abnormal aggression phenotype in
peripubertally stressed rats. Our results support a key role for GR actions
during peripubertal stress for the long-term programming of heightened
aggression. Strikingly, they also support the translational interest of testing
the effectiveness of mifepristone treatment to diminish reactive aggression in
early adversity-related human psychopathologies.
PMID- 29941979
TI - Silk protein nanofibers for highly efficient, eco-friendly, optically
translucent, and multifunctional air filters.
AB - New types of air filter technologies are being called because air pollution by
particulate matters (PMs) and volatile organic compounds has raised serious
concerns for public health. Conventional air filters have limited application and
poor degradability and they become non-disposable wastes after use. Here, we
report a highly efficient, eco-friendly, translucent, and multifunctional air
purification filter that is highly effective for reducing air pollution,
protecting the environment, and detecting hazardous chemical vapors encountered
in everyday life. Uniform silk protein nanofibers were directly generated on a
window screen by an electrospinning process. Optical properties (translucence and
scattering) of the silk nanofibrous air filters (SNAFs) are advantageous for
achieving viewability and controlling the room temperature. Air filtration
efficiencies of the fabricated SNAFs could reach up to 90% and 97% for PMs with
sizes under 2.5 and 10 MUm, respectively, exceeding the performances of
commercial semi-high-efficiency particulate air (semi-HEPA) filters. After use,
the SNAFs could be naturally degraded. Furthermore, we demonstrate the ability of
SNAFs impregnated with organic dyes to sense hazardous and volatile vapors
encountered in everyday life.
PMID- 29941980
TI - Non-invasive spinal vibration testing using ultrafast ultrasound imaging: A new
way to measure spine function.
AB - Ultrafast ultrasound imaging is used to capture driven spinal vibrations as a new
method for non-invasive spinal testing in living subjects. Previously, it has
been shown that accelerometer-based vibration testing in cadaveric models can
reveal the presence, location and magnitude of spinal pathology. However, this
process remains an invasive procedure as current non-invasive sensors are
inadequate. In this paper, the ability of non-invasive ultrafast ultrasound to
quantify in vivo vertebral vibration response across a broad range of frequencies
(10-100Hz) in anesthetized pig models is investigated. Close agreement with
invasive accelerometer measurements is achieved using the non-invasive ultrasound
method, opening up unique opportunities to investigate spinal pathologies.
PMID- 29941977
TI - Dorsal and ventral hippocampal adult-born neurons contribute to context fear
memory.
AB - The hippocampus contains one of the few neurogenic niches within the adult brain
the subgranular zone of the dentate gyrus. The functional significance of adult
born neurons in this region has been characterized using context fear
conditioning, a Pavlovian paradigm in which animals learn to associate a location
with danger. Ablation or silencing of adult-born neurons impairs both acquisition
and recall of contextual fear conditioning, suggesting that these neurons
contribute importantly to hippocampal memory. Lesion studies indicate that CFC
depends on neural activity in both the dorsal and ventral hippocampus, subregions
with unique extrahippocampal connectivity and behavioral functions. Because most
studies of adult neurogenesis have relied on methods that permanently ablate
neurogenesis throughout the entire hippocampus, little is known about how the
function of adult-born neurons varies along the dorsal-ventral axis. Using a
Nestin-CreERT2 mouse line to target the optogenetic silencer Archaerhodopsin to
adult-born neurons, we compared the contribution of dorsal and ventral adult-born
neurons to acquisition, recall, and generalization of CFC. Acquisition of CFC was
impaired when either dorsal or ventral adult-born neurons were silenced during
training. Silencing dorsal or ventral adult-born neurons during test sessions
decreased context-evoked freezing but did not impair freezing in a hippocampus
independent tone-shock freezing paradigm. Silencing adult-born neurons modestly
reduced generalization of fear. Our data indicate that adult-born neurons in the
dorsal and ventral hippocampus contribute to both memory acquisition and recall.
The comparatively large behavioral effects of silencing a small number of adult
born neurons suggest that these neurons make a unique and powerful contribution
to hippocampal function.
PMID- 29941981
TI - ADAM-like Decysin-1 (ADAMDEC1) is a positive regulator of Epithelial Defense
Against Cancer (EDAC) that promotes apical extrusion of RasV12-transformed cells.
AB - Recent studies have revealed that newly emerging transformed cells are often
eliminated from epithelia via cell competition with the surrounding normal
epithelial cells. However, it remains unknown whether and how soluble factors are
involved in this cancer preventive phenomenon. By performing stable isotope
labeling with amino acids in cell culture (SILAC)-based quantitative mass
spectrometric analyses, we have identified ADAM-like Decysin-1 (ADAMDEC1) as a
soluble protein whose expression is upregulated in the mix culture of normal and
RasV12-transformed epithelial cells. Expression of ADAMDEC1 is elevated in normal
epithelial cells co-cultured with RasV12 cells. Knockdown of ADAMDEC1 in the
surrounding normal cells substantially suppresses apical extrusion of RasV12
cells, suggesting that ADAMDEC1 secreted by normal cells positively regulate the
elimination of the neighboring transformed cells. In addition, we show that the
metalloproteinase activity of ADAMDEC1 is dispensable for the regulation of
apical extrusion. Furthermore, ADAMDEC1 facilitates the accumulation of filamin,
a crucial regulator of Epithelial Defense Against Cancer (EDAC), in normal cells
at the interface with RasV12 cells. This is the first report demonstrating that
an epithelial intrinsic soluble factor is involved in cell competition in
mammals.
PMID- 29941982
TI - Seroprevalence and risk factors for infection with Bartonella bacilliformis in
Loja province, Ecuador.
AB - The seroprevalence and epidemiology of Bartonella bacilliformis infection in the
Andean highlands of Ecuador is largely unknown. We conducted a sero-epidemiologic
survey of 319 healthy children aged 1-15 years living in six rural, mountain
communities in Loja Province, Ecuador. Blood was collected by finger stick onto
filter paper and dried, and the eluted sera analyzed for antibodies to B.
bacilliformis by rPap31 ELISA. Demographic, entomologic, and household variables
were assessed to investigate associated risk factors for antibody seropositivity
to B. bacilliformis. Seroprevalence of 28% was found among children in the study
communities. Increased risk of seropositivity was associated with the presence of
lumber piles near houses. Decreased risk of seropositivity was observed with the
presence of animal waste and incremental 100 meter increases in elevation.
Although investigation of clinical cases of Carrion's disease was not within the
scope of this study, our serology data suggest that infection of children with B.
bacilliformis is prevalent in this region of Ecuador and is largely unrecognized
and undiagnosed. This study highlights the need to further investigate the
prevalence, pathogenesis, epidemiology, and disease impact of this pathogen in
Ecuador.
PMID- 29941984
TI - Additive effects of the combined expression of soluble forms of GAS1 and PTEN
inhibiting glioblastoma growth.
AB - The overexpression of GAS1 (Growth Arrest Specific 1) in glioma cells induces
cell cycle arrest and apoptosis. We previously demonstrated that the apoptotic
process set off by GAS1 is caused by its capacity to inhibit the Glial cell
derived neurotrophic factor (GDNF)-mediated intracellular survival signaling
pathway. Whereas on the other hand, PTEN is a tumor suppressor, inactive in many
tumors, and both GAS1 and PTEN inhibit the PI3K/AKT pathway. Therefore, it is
relevant to investigate the potential additive effect of the overexpression of
GAS1 and PTEN on tumor growth. In particular, we employed secreted forms of both
GAS1 (tGAS1) and PTEN (PTEN-LONG, or PTEN-L) and tested their combined effect on
glioma cells. We observed that the co-expression of both the proteins inhibited
the growth of U-87 MG human glioblastoma cells more effectively than when
independently expressed, and decreased the activity of both AKT and ERK1/2.
Interestingly, the combination of the soluble forms was always the most effective
treatment. To improve the transfer of tGAS1 and PTEN-L, we employed a lentiviral
vector with a p2A peptide-enabled dual expression system that allowed the
generation of the two proteins using a single promoter (CMV), in equimolar
amounts. The viral vector reduced the growth of U-87 MG cells in vitro and had a
striking effect in inhibiting their proliferation after inoculating it into the
immunosuppressed mice. The present results support a potential adjuvant role for
the combined use of tGAS1 and PTEN-L in the treatment of glioblastoma.
PMID- 29941983
TI - Bryozoans are Major Modern Builders of South Atlantic Oddly Shaped Reefs.
AB - In major modern reef regions, either in the Indo-Pacific or the Caribbean,
scleractinian corals are described as the main reef framework builders, often
associated with crustose coralline algae. We used underwater cores to investigate
Late Holocene reef growth and characterise the main framework builders in the
Abrolhos Shelf, the largest and richest modern tropical reef complex in the South
Western Atlantic, a scientifically underexplored reef province. Rather than a
typical coralgal reef, our results show a complex framework building system
dominated by bryozoans. Bryozoans were major components in all cores and age
intervals (2,000 yrs BP), accounting for up to 44% of the reef framework, while
crustose coralline algae and coral accounted for less than 28 and 23%,
respectively. Reef accretion rates varied from 2.7 to 0.9 mm yr-1, which are
similar to typical coralgal reefs. Bryozoan functional groups encompassed 20 taxa
and Celleporaria atlantica (Busk, 1884) dominated the framework at all cores.
While the prevalent mesotrophic conditions may have driven suspension-feeders'
dominance over photoautotrophs and mixotrophs, we propose that a combination of
historical factors with the low storm-disturbance regime of the tropical South
Atlantic also contributed to the region's low diversity, and underlies the unique
mushroom shape of the Abrolhos pinnacles.
PMID- 29941985
TI - Ligand Binding Stabilizes Cellulosomal Cohesins as Revealed by AFM-based Single
Molecule Force Spectroscopy.
AB - The cohesin-dockerin receptor-ligand family is the key element in the formation
of multi-enzyme lignocellulose-digesting extracellular complexes called
cellulosomes. Changes in a receptor protein upon binding of a ligand - commonly
referred to as allostery - are not just essential for signalling, but may also
alter the overall mechanical stability of a protein receptor. Here, we measured
the change in mechanical stability of a library of cohesin receptor domains upon
binding of their dockerin ligands in a multiplexed atomic force microscopy-based
single-molecule force spectroscopy experiment. A parallelized, cell-free protein
expression and immobilization protocol enables rapid mechanical phenotyping of an
entire library of constructs with a single cantilever and thus ensures high
throughput and precision. Our results show that dockerin binding increases the
mechanical stability of every probed cohesin independently of its original
folding strength. Furthermore, our results indicate that certain cohesins undergo
a transition from a multitude of different folds or unfolding pathways to a
single stable fold upon binding their ligand.
PMID- 29941986
TI - Electrical Conductivity Distribution in Detonating Benzotrifuroxane.
AB - Electrical conductivity profile behind the detonation front in the
benzotrifuroxane (BTF) was measured using high-resolution technique. BTF is a
peculiar high explosive which is completely hydrogen-free: its molecular formula
is C6N6O6. Results are compared with the conductivity distributions in detonating
hexogen (RDX, C3H6N6O6) and triaminotrinitrobenzene based explosive (TATB,
C6H6N6O6). The conductivity in BTF was found to be similar to that observed in
the common explosives which contain hydrogen. Thus, the contribution of hydrogen
(e.g., ions produced by the dissociation of water) in the conductivity is minor,
both in the reaction zone and in the final detonation products. The
characteristics of the conductivity profiles generally support the idea of
contact conductivity through the connected structures of carbon particles formed
in the detonation wave.
PMID- 29941987
TI - Fabrication of 3D Fingerprint Phantoms via Unconventional Polycarbonate Molding.
AB - Fingerprint biometrics is a valuable and convenient security tool; every
fingerprint is highly detailed and unique, we always have them on "hand". Herein
we describe a novel bench-top method of making 3D fingerprint replicas (namely,
fingerprint phantoms) by exploring a unique microfabrication approach using
conventional polymeric materials, to aid the development of reliable and accurate
fingerprint biometrics. By pressing an impression of human fingerprints onto
solvent-softened plastic plates (e.g., polycarbonate chips), followed by casting
with polydimethylsiloxane (PDMS, a popular elastomer), we can produce a flexible,
nanoscale detailed, 3D reproduction of the fingerprint ("phantom"). By testing
with standard optical fingerprint scanners, we have shown that all three levels
of fingerprint details can be precisely recorded and match well with the original
fingerprint. Superior to artificial fingerprint patterns, these phantoms have the
exact 3D features of fingerprints and introduce no variability compared to human
sampling, which make them perfect targets for standardizing fingerprint scanners
and for biometric applications. We envision that the microcontact replication
protocol via unconventional PC molding promises a practical, bench-top,
instrumentation-free method to mass reproduce many other micro/nanostructures
with high fidelity.
PMID- 29941988
TI - Ultrathin amorphous carbon films synthesized by filtered cathodic vacuum arc used
as protective overcoats of heat-assisted magnetic recording heads.
AB - Despite numerous investigations of amorphous carbon (a-C) films, a comprehensive
study of the feasibility and optimization of sub-5-nm-thick a-C films deposited
onto the write pole of heat-assisted magnetic recording (HAMR) heads is lacking.
The main objective of this study was to identify the role of pulse substrate bias
voltage and C+ ion incidence angle on the structure and thickness of 1-4-nm-thick
a-C films deposited by a rather new thin-film deposition method, known as
filtered cathodic vacuum arc (FCVA). The cross-sectional structure of a-C films
synthesized under various FCVA conditions was examined by high-resolution
transmission electron microscopy (HRTEM), scanning transmission electron
microscopy (STEM), and electron energy loss spectroscopy (EELS). It was found
that film growth under process conditions of low-to-intermediate substrate bias
voltage (in the range of -25 to -100 V), low ion incidence angle (10 degrees ),
very short deposition time (6 s), and fixed other deposition parameters (65% duty
cycle of substrate pulse biasing and 1.48 * 1019 ions/m2.s ion flux) yields a-C
films of thickness <=4 nm characterized by a significant content (~50-60 at%) of
tetrahedral (sp3) carbon atom hybridization. A threshold where sp3 hybridization
is greatly reduced due to limited film growth was determined from the HRTEM/STEM
and EELS measurements. The results of this study demonstrate the viability of
FCVA to produce extremely thin and uniform protective a-C films with relatively
high sp3 contents for HAMR heads.
PMID- 29941989
TI - Translational control of depression-like behavior via phosphorylation of
eukaryotic translation initiation factor 4E.
AB - Translation of mRNA into protein has a fundamental role in neurodevelopment,
plasticity, and memory formation; however, its contribution in the
pathophysiology of depressive disorders is not fully understood. We investigated
the involvement of MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 and
2) and their target, eIF4E (eukaryotic initiation factor 4E), in depression-like
behavior in mice. Mice carrying a mutation in eIF4E for the MNK1/2
phosphorylation site (Ser209Ala, Eif4e ki/ki), the Mnk1/2 double knockout mice
(Mnk1/2-/-), or mice treated with the MNK1/2 inhibitor, cercosporamide, displayed
anxiety- and depression-like behaviors, impaired serotonin-induced excitatory
synaptic activity in the prefrontal cortex, and diminished firing of the dorsal
raphe neurons. In Eif4e ki/ki mice, brain IkappaBalpha, was decreased, while the
NF-kappaB target, TNFalpha was elevated. TNFalpha inhibition in Eif4e ki/ki mice
rescued, whereas TNFalpha administration to wild-type mice mimicked the
depression-like behaviors and 5-HT synaptic deficits. We conclude that eIF4E
phosphorylation modulates depression-like behavior through regulation of
inflammatory responses.
PMID- 29941990
TI - A novel EM concentrator with open-concentrator region based on multi-folded
transformation optics.
AB - Conventional concentrators with inhomogeneous coating materials that fully
enclose the destined region pose great challenges for fabrication. In this paper,
we propose to design an EM concentrator with homogeneous materials. Distinguished
from conventional ones, the elaborately designed EM concentrator features a
concentrator region that is open to the outer-world, which is achieved with multi
folded transformation optics method by compressing and folding the coating
materials to create window(s). Based on this concept, we also investigate open
rotator and open rotational-concentrator devices, which could simultaneously
rotate and store the EM waves in the central destined region. Due to the open
nature of our proposed designs, we believe they will find potential applications
in remote controlling with impressive new functionalities.
PMID- 29941991
TI - Phytate Decreases Formation of Advanced Glycation End-Products in Patients with
Type II Diabetes: Randomized Crossover Trial.
AB - Myo-inositol hexaphosphate (phytate; IP6) is a natural compound that is abundant
in cereals, legumes, and nuts and it has the ability to chelate metal cations.
The binding of IP6 to transition metals suggests that it could be used for the
treatment of metal-catalyzed protein glycation, which appears to trigger diabetes
related diseases. Our in vitro studies showed that IP6 reduced the formation of
Fe3+-catalyzed advanced glycation end-products (AGEs). This led us to perform a
randomized cross-over trial to investigate the impact of the daily consumption
IP6 on protein glycation in patients with type 2 diabetes mellitus (T2DM; n =
33). Thus, we measured AGEs, glycated hemoglobin (HbA1c), several vascular risk
factors, and urinary IP6 at baseline and at the end of the intervention period.
Patients who consumed IP6 supplements for 3 months had lower levels of
circulating AGEs and HbA1c than those who did not consume IP6. This is the first
report to show that consumption of IP6 inhibits protein glycation in patients
with T2DM. Considering that AGEs contribute to microvascular and macrovascular
complications in T2DM, our data indicates that dietary supplementation with IP6
should be considered as a therapy to prevent the formation of AGEs and therefore,
the development of diabetes-related diseases in patients with T2DM.
PMID- 29941992
TI - Plasmonic refractive index sensing using strongly coupled metal nanoantennas:
nonlocal limitations.
AB - Localized surface plasmon resonance based on coupled metallic nanoparticles has
been extensively studied in the refractive index sensing and the detection of
molecules. The amount of resonance peak-shift depends on the refractive index of
surrounding medium and the geometry/symmetry of plasmonic oligomers. It has
recently been found that as the feature size or the gap distance of plasmonic
nanostructures approaches several nanometers, quantum effects can change the
plasmon coupling in nanoparticles. However, most of the research on plasmonic
sensing has been done based on classical local calculations even for the
interparticle gap below ~3 nm, in which the nonlocal screening plays an important
role. Here, we theoretically investigate the nonlocal effect on the evolution of
various plasmon resonance modes in strongly coupled nanoparticle dimer and trimer
antennas with the gap down to 1 nm. Then, the refractive index sensing in these
nonlocal systems is evaluated and compared with the results in classical
calculations. We find that in the nonlocal regime, both refractive index
sensibility factor and figure of merit are actually smaller than their classical
counterparts mainly due to the saturation of plasmon shifts. These results would
be beneficial for the understanding of interaction between light and nonlocal
plasmonic nanostructures and the development of plasmonic devices such as
nanosensors and nanoantennas.
PMID- 29941994
TI - New drug blocks brain metastasis.
PMID- 29941993
TI - TIMP2 is a Poor Prognostic Factor and Predicts Metastatic Biological Behavior in
Gastric Cancer.
AB - To explore the prognostic related factors and mechanisms of gastric cancer (GC),
we performed the systematic analysis with integrated bioinformatics tools based
on multiple on-line datasets. With uni-variate COX analysis, we screened out 37
survival hazardous genes in GC. Further GO assays disclosed that the signatures
related with extracellular matrix and structure, and the functions of "cell
adhesion molecule binding" and "integrin binding" were the vital mechanisms of
disease progression, and tissue inhibitor of metalloproteinase-2 (TIMP2) was the
potential biomarker for prognosis. Based on GSEA, GSVA and GCN, TIMP2 was
demonstrated to interact with multiple integrin pathways and involve in the
regulation of EMT, cell adhesion, and angiogenesis of GC. The associations of
TIMP2 expression with reduced OS and RFS of patients were declared by Kaplan
Meier analysis, and further confirmed by 1000 internal bootstrap replications and
external KM plotter analysis. With multi-variate COX regression and time
dependent ROC analysis, we validated the prediction independency and capacity of
TIMP2 for prognosis. The relationships of TIMP2 with clinicopathological
characteristics were also uncovered. Taken together, our findings identify TIMP2
as the novel candidate biomarker for poorer outcome of GC patients, and revealed
the underlying functions of TIMP2 and the potential mechanisms for GC
progression.
PMID- 29941995
TI - Social dominance predicts hippocampal glucocorticoid receptor recruitment and
resilience to prenatal adversity.
AB - The developing fetus is highly sensitive to prenatal stress, which may alter
Hypothalamic-Pituitary-Adrenal (HPA) axis programming and increase the risk of
behavioral disorders. There is high variability among the human population,
wherein many offspring of stressed pregnancies display resilience to adversity,
while the remainder displays vulnerability. In order to identify biological
substrates mediating between resilience or vulnerability to prenatal adversity,
we exposed stress-resistant Dominant (Dom) and stress-sensitive Submissive (Sub)
mice to mild prenatal restraint stress (PRS, 45 min on gestational days (GD) 15,
16 and 17). We hypothesized that PRS would differentially alter prenatal
programming of limbic regions regulating the HPA axis and affect among Dom and
Sub offspring. Indeed, PRS increased Sub offspring's serum corticosterone, and
exaggerated their anxiety- and depressive-like behavior, while Dom offspring
remained resilient to the hormonal and behavioral consequences of PRS. Moreover,
PRS exposure markedly facilitated glucocorticoid receptor (GR) recruitment to the
hippocampus among Dom mice in response to restraint stress, which may be
responsible for their resilience to stressful challenge. These findings suggest
proclivity to adaptive or maladaptive prenatal programming of hippocampal GR
recruitment to be inheritable and predictable by social dominance or
submissiveness.
PMID- 29941996
TI - Population genomic data reveal extreme geographic subdivision and novel
conservation actions for the declining foothill yellow-legged frog.
AB - Genomic data have the potential to inform high resolution landscape genetic and
biological conservation studies that go far beyond recent mitochondrial and
microsatellite analyses. We characterize the relationships of populations of the
foothill yellow-legged frog, Rana boylii, a declining, "sentinel" species for
stream ecosystems throughout its range in California and Oregon. We generated
RADseq data and applied phylogenetic methods, hierarchical Bayesian clustering,
PCA and population differentiation with admixture analyses to characterize
spatial genetic structure across the species range. To facilitate direct
comparison with previous analyses, we included many localities and individuals
from our earlier work based on mitochondrial DNA. The results are striking, and
emphasize the power of our landscape genomic approach. We recovered five
extremely differentiated primary clades that indicate that R. boylii may be the
most genetically differentiated anuran yet studied. Our results provide better
resolution and more spatially consistent patterns than our earlier work,
confirming the increased resolving power of genomic data compared to single-locus
studies. Genomic structure is not equal across the species distribution.
Approximately half the range of R. boylii consists of a single, relatively
uniform population, while Sierra Nevada and coastal California clades are deeply,
hierarchically substructured with biogeographic breaks observed in other
codistributed taxa. Our results indicate that clades should serve as management
units for R. boylii rather than previously suggested watershed boundaries, and
that the near-extinct population from southwestern California is particularly
diverged, exhibits the lowest genetic diversity, and is a critical conservation
target for species recovery.
PMID- 29941997
TI - Accurate genomic prediction of Coffea canephora in multiple environments using
whole-genome statistical models.
AB - Genomic selection has been proposed as the standard method to predict breeding
values in animal and plant breeding. Although some crops have benefited from this
methodology, studies in Coffea are still emerging. To date, there have been no
studies describing how well genomic prediction models work across populations and
environments for different complex traits in coffee. Considering that predictive
models are based on biological and statistical assumptions, it is expected that
their performance vary depending on how well these assumptions align with the
true genetic architecture of the phenotype. To investigate this, we used data
from two recurrent selection populations of Coffea canephora, evaluated in two
locations, and single nucleotide polymorphisms identified by Genotyping-by
Sequencing. In particular, we evaluated the performance of 13 statistical
approaches to predict three important traits in the coffee-production of coffee
beans, leaf rust incidence and yield of green beans. Analyses were performed for
predictions within-environment, across locations and across populations to assess
the reliability of genomic selection. Overall, differences in the prediction
accuracy of the competing models were small, although the Bayesian methods showed
a modest improvement over other methods, at the cost of more computation time. As
expected, predictive accuracy for within-environment analysis, on average, were
higher than predictions across locations and across populations. Our results
support the potential of genomic selection to reshape traditional plant breeding
schemes. In practice, we expect to increase the genetic gain per unit of time by
reducing the length cycle of recurrent selection in coffee.
PMID- 29941998
TI - The Joint Association of Small for Gestational Age and Nighttime Sleep with Blood
Pressure in Childhood.
AB - Children born small for gestational age (SGA) are more likely to develop high
blood pressure. In prior studies, longer sleep duration is associated with lower
BP, and SGA is associated with shorter sleep duration in childhood. We
investigated whether sleep duration in early childhood modifies the association
between SGA and higher childhood SBP in 1178 children recruited at birth and
followed up to age 9 years. We ascertained birthweight and gestational age from
medical records. We derived child sleep duration from maternal questionnaire
interview. We calculated child SBP percentile according to U.S. reference data.
We defined elevated SBP as SBP >=75th percentile. In this sample, 154 (13.1%)
children were born SGA. Children born SGA had higher SBP percentiles and higher
risk of elevated SBP. Among children born SGA, those in the highest compared to
the lowest tertile for sleep had a 12.28 lower (-22.00, -2.57) SBP percentile and
0.44 (0.25 to 0.79) times lower risk of developing elevated SBP. Our data are
consistent with an interaction between SGA and sleep duration on childhood
elevated SBP (Pinteraction = 0.0056). In conclusion, in this prospective birth
cohort, longer sleep duration in early childhood may mitigate the blood pressure
raising effect of being born small.
PMID- 29941999
TI - Full rescue of an inactive olfactory receptor mutant by elimination of an
allosteric ligand-gating site.
AB - Ligand-gating has recently been proposed as a novel mechanism to regulate
olfactory receptor sensitivity. TAAR13c, the zebrafish olfactory receptor
activated by the death-associated odor cadaverine, appears to possess an
allosteric binding site for cadaverine, which was assumed to block progress of
the ligand towards the internal orthosteric binding-and-activation site. Here we
have challenged the suggested gating mechanism by modeling the entry tunnel for
the ligand as well as the ligand path inside the receptor. We report an entry
tunnel, whose opening is blocked by occupation of the external binding site by
cadaverine, confirming the hypothesized gating mechanism. A multistep docking
algorithm suggested a plausible path for cadaverine from the allosteric to the
orthosteric binding-and-activation site. Furthermore we have combined a gain-of
function gating site mutation and a loss-of-function internal binding site
mutation in one recombinant receptor. This receptor had almost wildtype ligand
affinities, consistent with modeling results that showed localized effects for
each mutation. A novel mutation of the suggested gating site resulted in
increased receptor ligand affinity. In summary both the experimental and the
modeling results provide further evidence for the proposed gating mechanism,
which surprisingly exhibits pronounced similarity to processes described for some
metabotropic neurotransmitter receptors.
PMID- 29942000
TI - HMGB2 is a novel adipogenic factor that regulates ectopic fat infiltration in
skeletal muscles.
AB - Although various surgical procedures have been developed for chronic rotator cuff
tear repair, the re-tear rate remains high with severe fat infiltration. However,
little is known about the molecular regulation of this process. Mesenchymal stem
cells (MSCs) in the intra-muscular space are origin of ectopic fat cells in
skeletal muscle. We have previously shown that high-mobility group box 2 (HMGB2),
which is a nuclear protein commonly associated with mesenchymal differentiation,
is involved in the early articular cartilage degeneration. In this study, we
addressed the role of HMGB2 in adipogenesis of MSCs and fat infiltration into
skeletal muscles. HMGB2 was highly expressed in undifferentiated MSCs and co
localized with platelet-derived growth factor receptor alpha (PDGFRA) known as an
MSC-specific marker, while their expressions were decreased during adipocytic
differentiation. Under the deficiency of HMGB2, the expressions of adipogenesis
related molecules were reduced, and adipogenic differentiation is substantially
impaired in MSCs. Moreover, HMGB2+ cells were generated in the muscle belly of
rat supraspinatus muscles after rotator cuff transection, and some of these cells
expressed PDGFRA in intra-muscular spaces. Thus, our findings suggest that the
enhance expression of HMGB2 induces the adipogenesis of MSCs and the fat
infiltration into skeletal muscles through the cascade of HMGB2-PDGFRA.
PMID- 29942001
TI - Host-plant induced changes in microbial community structure and midgut gene
expression in an invasive polyphage (Anoplophora glabripennis).
AB - Polyphagous insect herbivores possess diverse mechanisms to overcome challenges
of feeding in multiple plant species including, but not limited to,
transcriptional plasticity and associations with obligate or facultative
symbionts. The Asian longhorned beetle (Anoplophora glabripennis) is a
polyphagous wood-feeder capable of developing on over 100 tree species and, like
other polyphages, its genome contains amplifications of digestive and
detoxification genes. This insect also possesses a diverse gut microbial
community, which has the metabolic potential to augment digestive physiology.
While the genomic repertoires of A. glabripennis and its microbial community have
been studied previously, comparatively less is known about how the gut
transcriptome and community change in response to feeding in different hosts. In
this study, we show that feeding in two suitable hosts (Acer spp. and Populus
nigra) altered the expression levels of multicopy genes linked to digestion and
detoxification. However, feeding in a host with documented resistance (Populus
tomentosa) induced changes in the transcriptome and community beyond what was
observed in insects reared in P. nigra, including the downregulation of numerous
beta-glucosidases, odorant binding proteins, and juvenile hormone binding
proteins, the upregulation of several cuticular genes, and the loss of one major
bacterial family from the gut community.
PMID- 29942002
TI - Ikaros family zinc-finger 1 mutation is an independent factor for the poor
prognosis of adult B-cell acute lymphoblastic leukemia, and allogeneic
hematopoietic stem cell transplantation can improve clinical outcomes.
AB - To investigate the prognosis of patients with adult B-cell acute lymphoblastic
leukemia (B-ALL) with Ikaros family zinc-finger 1 (IKZF1) mutation and determine
the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in
improving the clinical outcome, we detected the IKZF1 mutation and BCR-ABL fusion
gene at diagnosis in the bone marrow of 164 adult patients with B-ALL, and
analyzed the clinical data of these patients retrospectively. Our analysis showed
that grade III-IV acute graft-versus-host disease and IKZF1 mutation in the
transplantation group and age and IKZF1 mutation in the non-transplantation group
were independent factors for poor prognosis by univariate and multivariate
analyses.The 3-year overall survival (OS) and leukemia-free survival (LFS) rates
were much lower in the IKZF1+/BCR-ABL+ subgroup than in the IKZF1+/BCR-ABL- and
IKZF1-/BCR-ABL- subgroups in both the transplantation and non-transplantation
groups. The 3-year OS and LFS rates were significantly higher in the
transplantation group than in the non-transplantation group with IKZF1
mutation.The study demonstrated that IKZF1 mutation was an independent factor
indicating the poor prognosis of adult B-ALL and much worse prognosis in the BCR
ABL+ subgroup in both non-transplantation and transplantation groups. However,
allo-HSCT significantly improved the OS and LFS of patients and also their
clinical outcomes.
PMID- 29942004
TI - Author Correction: Structural prediction of protein models using distance
restraints derived from cross-linking mass spectrometry data.
AB - In the version of this article initially published online, the authors used
incorrectly defined restraints for specifying the distance between residues when
using the HADDOCK portal. Following the publication of a Correspondence by the
developers of the HADDOCK portal (Nat. Protoc. https://dx.doi.org/10.1038/s41596
018-0017-6, 2018) and a Reply by the authors of the Protocol (Nat. Protoc.
https://dx.doi.org/10.1038/s41596-018-0018-5, 2018), the syntax in step 21 has
been corrected. In addition, the input files (available as Supplementary Data 5
7) have been replaced.
PMID- 29942005
TI - Defining distance restraints in HADDOCK.
PMID- 29942003
TI - 2-[2-(4-(trifluoromethyl)phenylamino)thiazol-4-yl]acetic acid (Activator-3) is a
potent activator of AMPK.
AB - AMPK is considered as a potential high value target for metabolic disorders.
Here, we present the molecular modeling, in vitro and in vivo characterization of
Activator-3, 2-[2-(4-(trifluoromethyl)phenylamino)thiazol-4-yl]acetic acid, an
AMP mimetic and a potent pan-AMPK activator. Activator-3 and AMP likely share
common activation mode for AMPK activation. Activator-3 enhanced AMPK
phosphorylation by upstream kinase LKB1 and protected AMPK complex against
dephosphorylation by PP2C. Molecular modeling analyses followed by in vitro
mutant AMPK enzyme assays demonstrate that Activator-3 interacts with R70 and
R152 of the CBS1 domain on AMPK gamma subunit near AMP binding site. Activator-3
and C2, a recently described AMPK mimetic, bind differently in the gamma subunit
of AMPK. Activator-3 unlike C2 does not show cooperativity of AMPK activity in
the presence of physiological concentration of ATP (2 mM). Activator-3 displays
good pharmacokinetic profile in rat blood plasma with minimal brain penetration
property. Oral treatment of High Sucrose Diet (HSD) fed diabetic rats with 10
mg/kg dose of Activator-3 once in a day for 30 days significantly enhanced
glucose utilization, improved lipid profiles and reduced body weight,
demonstrating that Activator-3 is a potent AMPK activator that can alleviate the
negative metabolic impact of high sucrose diet in rat model.
PMID- 29942006
TI - Reply to 'Defining distance restraints in HADDOCK'.
PMID- 29942007
TI - Coherent control theory and experiment of optical phonons in diamond.
AB - The coherent control of optical phonons has been experimentally demonstrated in
various physical systems. While the transient dynamics for optical phonons can be
explained by phenomenological models, the coherent control experiment cannot be
explained due to the quantum interference. Here, we theoretically propose the
generation and detection processes of the optical phonons and experimentally
confirm our theoretical model using the diamond optical phonon by the doublepump
probe type experiment.
PMID- 29942009
TI - Sea surface temperature predicts the movements of an Arctic cetacean: the bowhead
whale.
AB - The effects of climate change constitute a major concern in Arctic waters due to
the rapid decline of sea ice, which may strongly alter the movements and habitat
availability of Arctic marine mammals. We tracked 98 bowhead whales by satellite
over an 11-year period (2001-2011) in Baffin Bay - West Greenland to investigate
the environmental drivers (specifically sea surface temperature and sea ice)
involved in bowhead whale's movements. Movement patterns differed according to
season, with aggregations of whales found at higher latitudes during spring and
summer likely in response to sea-ice retreat and increasing sea temperature (SST)
facilitated by the warm West Greenland Current. In contrast, the whales moved
further south in response to sea temperature decrease during autumn and winter.
Statistical models indicated that the whales targeted a narrow range of SSTs from
-0.5 to 2 degrees C. Sea surface temperatures are predicted to undergo a marked
increase in the Arctic, which could expose bowhead whales to both thermal stress
and altered stratification and vertical transport of water masses. With such
profound changes, bowhead whales may face extensive habitat loss. Our results
highlight the need for closer investigation and monitoring in order to predict
the extent of future distribution changes.
PMID- 29942008
TI - Towards a gene regulatory network shaping the fins of the Princess cichlid.
AB - Variation in fin shape and size contributes to the outstanding morphological
diversity of teleost fishes, but the regulation of fin growth has not yet been
studied extensively outside the zebrafish model. A previous gene expression study
addressing the ornamental elongations of unpaired fins in the African cichlid
fish Neolamprologus brichardi identified three genes (cx43, mmp9 and sema3d) with
strong and consistent expression differences between short and elongated fin
regions. Remarkably, the expression patterns of these genes were not consistent
with inferences on their regulatory interactions in zebrafish. Here, we identify
a gene expression network (GRN) comprising cx43, mmp9, and possibly also sema3d
by a stepwise approach of identifying co-expression modules and predicting their
upstream regulators. Among the transcription factors (TFs) predicted as potential
upstream regulators of 11 co-expressed genes, six TFs (foxc1, foxp1, foxd3, myc,
egr2, irf8) showed expression patterns consistent with their cooperative
transcriptional regulation of the gene network. Some of these TFs have already
been implicated in teleost fish fin regeneration and formation. We particularly
discuss the potential function of foxd3 as driver of the network and its role in
the unexpected gene expression correlations observed in N. brichardi.
PMID- 29942011
TI - Development of an optimal imaging strategy for selection of patients for affibody
based PNA-mediated radionuclide therapy.
AB - Affibody molecules are engineered scaffold proteins, which demonstrated excellent
binding to selected tumor-associated molecular abnormalities in vivo and highly
sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics.
Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based
pretargeted radionuclide therapy using beta-emitting radionuclide 177Lu extended
significantly survival of mice bearing human Her2-expressing tumor xenografts. In
this study, we evaluated two approaches to use positron emission tomography (PET)
for stratification of patients for affibody-based pretargeting therapy. The
primary targeting probe ZHER2:342-SR-HP1 and the secondary probe HP2 (both
conjugated with DOTA chelator) were labeled with the positron-emitting
radionuclide 68Ga. Biodistribution of both probes was measured in BALB/C nu/nu
mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145
xenografts with low Her2 expression. 68Ga-HP2 was evaluated in the pretargeting
setting. Tumor uptake of both probes was compared with the uptake of pretargeted
177Lu-HP2. The uptake of both 68Ga-ZHER2:342-SR-HP1 and 68Ga-HP2 depended on Her2
expression level providing clear discrimination of between tumors with high and
low Her2 expression. Tumor uptake of 68Ga-HP2 correlated better with the uptake
of 177Lu-HP2 than the uptake of 68Ga-ZHER2:342-SR-HP1. The use of 68Ga-HP2 as a
theranostics counterpart would be preferable approach for clinical translation.
PMID- 29942013
TI - Making connections.
PMID- 29942010
TI - Mutually exclusive acetylation and ubiquitylation of the splicing factor SRSF5
control tumor growth.
AB - Most tumor cells take up more glucose than normal cells. Splicing dysregulation
is one of the molecular hallmarks of cancer. However, the role of splicing factor
in glucose metabolism and tumor development remains poorly defined. Here, we show
that upon glucose intake, the splicing factor SRSF5 is specifically induced
through Tip60-mediated acetylation on K125, which antagonizes Smurf1-mediated
ubiquitylation. SRSF5 promotes the alternative splicing of CCAR1 to produce
CCAR1S proteins, which promote tumor growth by enhancing glucose consumption and
acetyl-CoA production. Conversely, upon glucose starvation, SRSF5 is deacetylated
by HDAC1, and ubiquitylated by Smurf1 on the same lysine, resulting in
proteasomal degradation of SRSF5. The CCAR1L proteins accumulate to promote
apoptosis. Importantly, SRSF5 is hyperacetylated and upregulated in human lung
cancers, which correlates with increased CCAR1S expression and tumor progression.
Thus, SRSF5 responds to high glucose to promote cancer development, and SRSF5
CCAR1 axis may be valuable targets for cancer therapeutics.
PMID- 29942012
TI - Evidence for close-range hunting by last interglacial Neanderthals.
AB - Animal resources have been part of hominin diets since around 2.5 million years
ago, with sharp-edged stone tools facilitating access to carcasses. How exactly
hominins acquired animal prey and how hunting strategies varied through time and
space is far from clear. The oldest possible hunting weapons known from the
archaeological record are 300,000 to 400,000-year-old sharpened wooden staves.
These may have been used as throwing and/or close-range thrusting spears, but
actual data on how such objects were used are lacking, as unambiguous lesions
caused by such weapon-like objects are unknown for most of human prehistory.
Here, we report perforations observed on two fallow deer skeletons from Neumark
Nord, Germany, retrieved during excavations of 120,000-year-old lake shore
deposits with abundant traces of Neanderthal presence. Detailed studies of the
perforations, including micro-computed tomography imaging and ballistic
experiments, demonstrate that they resulted from the close-range use of thrusting
spears. Such confrontational ways of hunting require close cooperation between
participants, and over time may have shaped important aspects of hominin biology
and behaviour.
PMID- 29942015
TI - Childhood conditions set the balance.
PMID- 29942014
TI - Sex begets sexes.
PMID- 29942016
TI - Childhood ecology influences salivary testosterone, pubertal age and stature of
Bangladeshi UK migrant men.
AB - Male reproductive investment is energetically costly, and measures of human
reproductive steroid hormones (testosterone), developmental tempo (pubertal
timing) and growth (stature) correlate with local ecologies at the population
level. It is unclear whether male reproductive investment in later life is 'set'
during childhood development, mediated through adulthood, or varies by ethnicity.
Applying a life-course model to Bangladeshi migrants to the United Kingdom, here
we investigate plasticity in human male reproductive function resulting from
childhood developmental conditions. We hypothesized that childhood ecology shapes
adult trade-offs between reproductive investment and/or other fitness-related
traits. We predicted correspondence between these traits and developmental timing
of exposure to ecological constraints (Bangladesh) or conditions of surplus
(United Kingdom). We compared: Bangladesh sedentees (n = 107); Bangladeshi men
who migrated in childhood to the United Kingdom (n = 59); migrants who arrived in
adulthood (n = 75); second-generation UK-born and raised children of Bangladeshi
migrants (n = 56); and UK-born ethnic Europeans (n = 62). Migration before
puberty predicted higher testosterone and an earlier recalled pubertal age
compared with Bangladeshi sedentees or adult migrants, with more pronounced
differences in men who arrived before the age of eight. Second-generation
Bangladeshis were taller, with higher testosterone than sedentees and adult
migrants, and higher waking testosterone than Europeans. Age-related testosterone
profiles varied by group, declining in UK migrants, increasing in sedentees, and
having no significant relationship within UK-born groups. We conclude that male
reproductive function apparently remains plastic late into childhood, is
independent of Bengali or European ethnicity, and shapes physiological trade-offs
later in life.
PMID- 29942017
TI - Making an impact.
PMID- 29942018
TI - Dates for Neanderthal art and symbolic behaviour are reliable.
PMID- 29942019
TI - The rate of facultative sex governs the number of expected mating types in
isogamous species.
AB - It is unclear why sexually reproducing isogamous species frequently contain just
two self-incompatible mating types. Deterministic theory suggests that since rare
novel mating types experience a selective advantage (by virtue of their many
potential partners), the number of mating types should consistently grow.
However, in nature, species with thousands of mating types are exceedingly rare.
Several competing theories for the predominance of species with two mating types
exist, yet they lack an explanation for how many are possible and in which
species to expect high numbers. Here, we present a theoretical null model that
explains the distribution of mating type numbers using just three biological
parameters: mutation rate, population size and the rate of sex. If the number of
mating types results from a mutation-extinction balance, the rate of sexual
reproduction plays a crucial role. If sex is facultative and rare (a very common
combination in isogamous species), mating type diversity will remain low. In this
rare sex regime, small fitness differences between the mating types lead to more
frequent extinctions, further lowering mating type diversity. We also show that
the empirical literature supports the role of drift and facultativeness of sex as
a determinant of mating type dynamics.
PMID- 29942021
TI - Social tipping points in animal societies in response to heat stress.
AB - Living systems sometimes experience abrupt tipping points in response to stress.
Here we investigate the factors contributing to the appearance of such abrupt
state transitions in animal societies. We first construct a mathematical account
of how the personality compositions of societies could alter their propensity to
shift from calm to violent states in response to thermal stress. To evaluate our
model, we subjected experimental societies of the spider Anelosimus studiosus to
heat stress. We demonstrate that both colony size and personality composition
influence the timing of and recoverability from sudden transitions in social
state. Groups composed of aggressive personalities transitioned into violent
within-group dynamics sooner during heating, and also resisted recovery to
baseline non-aggressive behaviour during cooling. We further observed hysteresis
in groups composed of aggressive individuals, where group behaviour depended
strongly on whether the colony had previously been in a calm or agitated state.
These results demonstrate that a society's susceptibility to sudden state shifts
and their recoverability from them can be driven by the personalities of their
constituents.
PMID- 29942020
TI - Early metazoan cell type diversity and the evolution of multicellular gene
regulation.
AB - A hallmark of metazoan evolution is the emergence of genomic mechanisms that
implement cell-type-specific functions. However, the evolution of metazoan cell
types and their underlying gene regulatory programmes remains largely
uncharacterized. Here, we use whole-organism single-cell RNA sequencing to map
cell-type-specific transcription in Porifera (sponges), Ctenophora (comb jellies)
and Placozoa species. We describe the repertoires of cell types in these non
bilaterian animals, uncovering diverse instances of previously unknown molecular
signatures, such as multiple types of peptidergic cells in Placozoa. Analysis of
the regulatory programmes of these cell types reveals variable levels of
complexity. In placozoans and poriferans, sequence motifs in the promoters are
predictive of cell-type-specific programmes. By contrast, the generation of a
higher diversity of cell types in ctenophores is associated with lower
specificity of promoter sequences and the existence of distal regulatory
elements. Our findings demonstrate that metazoan cell types can be defined by
networks of transcription factors and proximal promoters, and indicate that
further genome regulatory complexity may be required for more diverse cell type
repertoires.
PMID- 29942022
TI - The utility of height for the Ediacaran organisms of Mistaken Point.
AB - Ediacaran fossil communities consist of the oldest macroscopic eukaryotic
organisms. Increased size (height) is hypothesized to be driven by competition
for water column resources, leading to vertical/epifaunal tiering and
morphological innovations such as stems. Using spatial analyses, we find no
correlation between tiering and resource competition, and that stemmed organisms
are not tiered. Instead, we find that height is correlated with greater offspring
dispersal, demonstrating the importance of colonization potential over resource
competition.
PMID- 29942023
TI - Genetic association and functional analysis of rs7903456 in FAM35A gene and
hyperuricemia: a population based study.
AB - Recent studies have identified SNP rs7903456 of FAM35A to be associated with
gout. Because of the close connections between hyperuricemia and gout, we
hypothesized that the effect of rs7903456 on gout might be mediated by
hyperuricemia or its related quantitative trait, uric acid level. We investigated
the association between 31 SNPs of FAM35A, including rs7903456, and hyperuricemia
based on 2,773 hyperuricemia patients and controls. We fitted a simple model for
each of these 31 SNPs to screen the candidate SNP for further analyses. Moreover,
we selected potential confounders and fitted a multivariate model to investigate
the adjusted effects of the targeted SNPs. Both disease status of hyperuricemia
and blood uric acid level were considered as the main phenotype. We have
identified rs7903456 to be associated with hyperuricemia and uric acid level. The
significant signal was identified between rs7903456 and uric acid level after
adjusted by several potential confounders. Our findings showed that the T allele
of rs7903456 could increase the uric acid level by ~10 mmol/L on average after
adjusting several biochemical and clinical variables. Our findings indicated that
the previously identified effects of rs7903456 on gout might partly be mediated
by its effect on uric acid levels.
PMID- 29942024
TI - Relationship between Optical Intensity on Optical Coherence Tomography and
Retinal Ischemia in Branch Retinal Vein Occlusion.
AB - Branch retinal vein occlusion (BRVO) may be complicated with retinal ischemia in
some cases. The purpose of the current study is to investigate the relationship
between optical intensity on optical coherence tomography (OCT) and retinal
ischemia in BRVO. Twenty-seven eyes diagnosed with BRVO without macular edema
were classified into two groups based on the presence or absence of retinal
ischemia. The optical intensity of inner retinal layers and photoreceptor inner
segment ellipsoid zone/retinal pigment epithelium layer (ISe/RPE) in the affected
and unaffected regions were measured on OCT. Their ratio (Optical intensity
ratio, OIR) was calculated and compared between affected and unaffected region.
In the retinal ischemia group, the optical intensity of inner retinal layers was
higher in the affected region compared to the unaffected region while the optical
intensity of ISe/RPE was low. The OIR was significantly higher in the affected
region compared to control (0.83 +/- 0.17 vs 0.68 +/- 0.09, p < 0.001). However,
in the non-ischemic group, there was no significant difference between the
affected and unaffected region. The BCVA was moderately correlated with OIR of
affected region (r = 0.489, p = 0.010). Our study suggests that optical intensity
ratio on OCT is correlated with retinal ischemia in BRVO.
PMID- 29942025
TI - A Markovian Approach towards Bacterial Size Control and Homeostasis in Anomalous
Growth Processes.
AB - Regardless of the progress achieved during recent years, the mechanisms coupling
growth and division to attain cell size homeostasis in bacterial populations are
still not well understood. In particular, there is a gap of knowledge about the
mechanisms controlling anomalous growth events that are ubiquitous even in wild
type phenotypes. Thus, when cells exceed the doubling size the divisome dynamics
sets a characteristic length scale that suggests a sizer property. Yet, it has
been recently shown that the size at birth and the size increment still satisfy
an adder-like correlation. Herein we propose a Markov chain model, that we
complement with computational and experimental approaches, to clarify this issue.
In this context, we show that classifying cells as a function of the
characteristic size set by the divisome dynamics provides a compelling framework
to understand size convergence, growth, and division at the large length scale,
including the adaptation to, and rescue from, filamentation processes. Our
results reveal the independence of size homeostasis on the division pattern of
long cells and help to reconcile sizer concepts at the single cell level with an
adder-like behavior at a population level.
PMID- 29942026
TI - A genome-wide mutation analysis method enabling high-throughput identification of
chemical mutagen signatures.
AB - Trinucleotide mutational signatures extracted from cancer genomes provide clues
useful in understanding the roles of mutagens and mutagenic mechanisms in cancer
development. The lack of a simple method for genome-wide analysis of alterations
induced by mutagens hampers the identification of trinucleotide signatures of
mutagen exposure and evaluation of their relationships with human cancers. Here,
we describe a novel approach to facilitate analysis of chemically induced
mutations in bacterial cells by detection of increased frequencies of base
substitutions after mutagen exposure, using paired-end overlapping next
generation sequencing. DNA samples from Salmonella typhimurium strain TA100,
exposed to three alkylating agents, ethylnitrosourea (ENU), methylnitrosourea
(MNU), and ethyl methansulphonate (EMS), were analysed. The G:C > A:T mutation
frequency was increased in all samples, whereas A:T base pair substitution
frequencies were increased specifically in samples exposed to ENU, consistent
with previous reports. Mutation patterns in the context of 96 possible
trinucleotide formats in these samples exhibited a sharp peak corresponding to an
NpCpY consensus sequence, which is similar to the mutational signature of
alkylating agents in human cancer. These results indicate that our approach can
be useful in facilitating the understanding of mechanisms underlying chemical
mutagenicity and for identification of unknown causal mutagens in human cancer.
PMID- 29942027
TI - Influencing the adhesion properties and wettability of mucin protein films by
variation of the environmental pH.
AB - Mucins, the main component of the mucus secretions of goblet and epithelial
cells, are known for exhibiting a different behaviour in accordance with their
surrounding environment (i.e. among others the environmental pH), which induces a
drastic change in their measured mechanical properties. In this work, we have
first employed Atomic Force Microscopy (AFM) in Force Spectroscopy mode to
evaluate the adhesion of porcine mucin films at the nanoscale, and the changes
caused in this particular factor by a pH variation between 7.0 and 4.0, both
quite common values in biological conditions. Measurements also involved
additional varying factors such as the indenting tip chemistry (hydrophobic vs
hydrophilic), its residence time on the measured film (0, 1 and/or 2 seconds),
and increasing pulling rates (ranging from 0.1 up to 10 um/s). A second approach
regarded the macroscale behaviour of the films, due to their potential
applicability in the development of a new set of stimuli-responsive biomaterials.
This was possible by means of complementary Wilhelmy plate method (to test the
wetting properties) and cell proliferation studies on films previously exposed to
the corresponding pH solution. According to our results, treatment with lowest pH
(4.0) provides porcine mucin with a more hydrophilic character, showing a much
stronger adhesion for analogous chemistries, as well as enhanced capability for
cell attachment and proliferation, which opens new pathways for their future use
and consideration as scaffold-forming material.
PMID- 29942028
TI - Contrasting nickel and zinc hyperaccumulation in subspecies of Dichapetalum
gelonioides from Southeast Asia.
AB - Hyperaccumulator plants have the unique ability to concentrate specific elements
in their shoot in concentrations that can be thousands of times greater than in
normal plants. Whereas all known zinc hyperaccumulator plants are facultative
hyperaccumulators with only populations on metalliferous soils hyperaccumulating
zinc (except for Arabidopsis halleri and Noccaea species that hyperaccumulate
zinc irrespective of the substrate), the present study discovered that
Dichapetalum gelonioides is the only (zinc) hyperaccumulator known to occur
exclusively on 'normal' soils, while hyperaccumulating zinc. We recorded
remarkable foliar zinc concentrations (10 730 ug g-1, dry weight) in Dichapetalum
gelonioides subsp. sumatranum growing on 'normal' soils with total soil zinc
concentrations of only 20 ug g-1. The discovery of zinc hyperaccumulation in this
tropical woody plant, especially the extreme zinc concentrations in phloem and
phloem-fed tissues (reaching up to 8465 ug g-1), has possible implications for
advancing zinc biofortification in Southeast Asia. Furthermore, we report
exceptionally high foliar nickel concentrations in D. subsp. tuberculatum (30 260
ug g-1) and >10 wt% nickel in the ash, which can be exploited for agromining. The
unusual nickel and zinc accumulation behaviour suggest that Dichapetalum-species
may be an attractive model to study hyperaccumulation and hypertolerance of these
elements in tropical hyperaccumulator plants.
PMID- 29942030
TI - Vibration and damping characteristics of 3D printed Kagome lattice with
viscoelastic material filling.
AB - Constrained layer dampers (CLD) are in widespread use for passive vibration
damping, in applications including aerospace structures. However, the introducing
of the damping layer can reduce the stiffness of the sandwich structures. A
viscoelastic material filling (VMF) is chosen to balance structural and
vibrational performance of lattice truss in this work. The recently brought
forward 3D Kagome truss with face sheet was manufactured by selective laser
sintering technology and the thermosetting polyurethane was chosen as the
viscoelastic filling material. A novel complex modal analysis finite element
method for Hybrid composite lattice truss sandwich is introduced in this paper.
Dynamic analysis experiment results show that the VMF method is found to be
effective in reducing the vibration amplitude and it has the potential for band
gap design. The VMF method can provide high stiffness at low mass and
considerable vibrational performance at low cost and it can be considered as a
general vibration design method in lattice truss manufacture.
PMID- 29942029
TI - Texture analysis of protein deposits produced by droplet evaporation.
AB - The deposit patterns derived from droplet evaporation allow current development
of medical tests and new strategies for diagnostic in patients. For such purpose,
the development and implementation of algorithms capable of characterizing and
differentiating deposits are crucial elements. We report the study of deposit
patterns formed by the droplet evaporation of binary mixtures of proteins
containing NaCl. Optical microscopy reveals aggregates such as tip arrow-shaped,
dendritic and semi-rosette patterns, needle-like and scalloped lines structures,
as well as star-like and prism-shaped salt crystals. We use the first-order
statistics (FOS) and gray level co-occurrence matrix (GLCM) to characterize the
complex texture of deposit patterns. Three significant findings arise from this
analysis: first, the FOS and GLCM parameters structurally characterize protein
deposits. Secondly, they conform to simple exponential laws that change as a
function of the NaCl concentration. Finally, the parameters are capable of
revealing the different structural changes that occur during the droplet
evaporation.
PMID- 29942031
TI - Parasitic interference.
PMID- 29942032
TI - A novel adenovirus isolated from the Egyptian fruit bat in South Africa is
closely related to recent isolates from China.
AB - Recently a number of novel adenoviruses have been isolated from diverse bat
species and from diverse geographical locations. We describe the isolation of a
novel adenovirus (Family Adenoviridae, genus Mastadenovirus) from a pool of liver
and spleen tissue of an apparently healthy wild-caught Egyptian fruit bat
(Rousettus aegyptiacus) in South Africa. Genetically the virus is most closely
related to four mastadenoviruses recently isolated in China, from Miniopterus
schreibersi and Rousettus leschenaultii bats, which are highly divergent from
previously identified bat adenoviruses. The length of the Rousettus aegyptiacus
adenovirus-3085 (RaegAdV-3085) genome, at 29,342 bp is similar to its closest
relatives, and contains 27 open reading frames. The RaegAdV-3085 genome has a low
G + C content (36.4%) relative to other viruses in the genus (between 43.6 and
63.9%) but similar to its closest relatives. The inverted terminal repeat (ITR)
of RaegAdV-3085 is only 40 bp compared to between 61 and 178 bp of its closest
relatives. The discovery of RaegAdV-3085 expands the diversity of known
adenoviruses in bats and might represent a member of a new mastadenovirus species
in bats.
PMID- 29942034
TI - Author Correction: Prioritizing monitoring and conservation efforts for fish
spawning aggregations in the U.S. Gulf of Mexico.
AB - A correction to this article has been published and is linked from the HTML and
PDF versions of this paper. The error has not been fixed in the paper.
PMID- 29942033
TI - Site-specific characterization of endogenous SUMOylation across species and
organs.
AB - Small ubiquitin-like modifiers (SUMOs) are post-translational modifications that
play crucial roles in most cellular processes. While methods exist to study
exogenous SUMOylation, large-scale characterization of endogenous SUMO2/3 has
remained technically daunting. Here, we describe a proteomics approach
facilitating system-wide and in vivo identification of lysines modified by
endogenous and native SUMO2. Using a peptide-level immunoprecipitation enrichment
strategy, we identify 14,869 endogenous SUMO2/3 sites in human cells during heat
stress and proteasomal inhibition, and quantitatively map 1963 SUMO sites across
eight mouse tissues. Characterization of the SUMO equilibrium highlights striking
differences in SUMO metabolism between cultured cancer cells and normal tissues.
Targeting preferences of SUMO2/3 vary across different organ types, coinciding
with markedly differential SUMOylation states of all enzymes involved in the SUMO
conjugation cascade. Collectively, our systemic investigation details the
SUMOylation architecture across species and organs and provides a resource of
endogenous SUMOylation sites on factors important in organ-specific functions.
PMID- 29942035
TI - High-performance solid state supercapacitors assembling graphene interconnected
networks in porous silicon electrode by electrochemical methods using 2,6
dihydroxynaphthalen.
AB - The challenge for conformal modification of the ultra-high internal surface of
nanoporous silicon was tackled by electrochemical polymerisation of 2,6
dihydroxynaphthalene using cyclic voltammetry or potentiometry and, notably,
after the thermal treatment (800 degrees C, N2, 4 h) an assembly of
interconnected networks of graphene strongly adhering to nanoporous silicon
matrix resulted. Herein we demonstrate the achievement of an easy scalable
technology for solid state supercapacitors on silicon, with excellent
electrochemical properties. Accordingly, our symmetric supercapacitors (SSC)
showed remarkable performance characteristics, comparable to many of the best
high-power and/or high-energy carbon-based supercapacitors, their figures of
merit matching under battery-like supercapacitor behaviour. Furthermore, the
devices displayed high specific capacity values along with enhanced capacity
retention even at ultra-high rates for voltage sweep, 5 V/s, or discharge current
density, 100 A/g, respectively. The cycling stability tests performed at
relatively high discharge current density of 10 A/g indicated good capacity
retention, with a superior performance demonstrated for the electrodes obtained
under cyclic voltammetry approach, which may be ascribed on the one hand to a
better coverage of the porous silicon substrate and, on the other hand, to an
improved resilience of the hybrid electrode to pore clogging.
PMID- 29942036
TI - Body-size increase in crinoids following the end-Devonian mass extinction.
AB - The Devonian period ended with one of the largest mass extinctions in the Earth
history. It comprised a series of separate events, which eliminated many marine
species and led to long-term post-extinction reduction in body size in some
groups. Surprisingly, crinoids were largely unaffected by these extinction events
in terms of diversity. To date, however, no study examined the long-term body
size trends of crinoids over this crucial time interval. Here we compiled the
first comprehensive data sets of sizes of calyces for 262 crinoid genera from the
Frasnian-Visean. We found that crinoids have not experienced long-term reduction
in body size after the so-called Hangenberg event. Instead, size distributions of
calyces show temporal heterogeneity in the variance, with an increase in both the
mean and maximum biovolumes between the Famennian and Tournaisian. The minimum
biovolume, in turn, has remained constant over the study interval. Thus, the
observed pattern seems to fit a Brownian motion-like diffusion model.
Intriguingly, the same model has been recently invoked to explain morphologic
diversification within the eucladid subclade during the Devonian-early
Carboniferous. We suggest that the complex interplay between abiotic and biotic
factors (i.e., expansion of carbonate ramps and increased primary productivity,
in conjunction with predatory release after extinction of Devonian-style
durophagous fishes) might have been involved not only in the early Mississippian
diversity peak of crinoids, but possibly also in their overall passive expansion
into larger body-size niches.
PMID- 29942037
TI - The mysterious origins of microglia.
PMID- 29942038
TI - Stressing the other paraventricular nucleus.
PMID- 29942039
TI - Investigating large-scale brain dynamics using field potential recordings:
analysis and interpretation.
AB - New technologies to record electrical activity from the brain on a massive scale
offer tremendous opportunities for discovery. Electrical measurements of large
scale brain dynamics, termed field potentials, are especially important to
understanding and treating the human brain. Here, our goal is to provide best
practices on how field potential recordings (electroencephalograms,
magnetoencephalograms, electrocorticograms and local field potentials) can be
analyzed to identify large-scale brain dynamics, and to highlight critical issues
and limitations of interpretation in current work. We focus our discussion of
analyses around the broad themes of activation, correlation, communication and
coding. We provide recommendations for interpreting the data using forward and
inverse models. The forward model describes how field potentials are generated by
the activity of populations of neurons. The inverse model describes how to infer
the activity of populations of neurons from field potential recordings. A
recurring theme is the challenge of understanding how field potentials reflect
neuronal population activity given the complexity of the underlying brain
systems.
PMID- 29942040
TI - Author Correction: Microglial immune checkpoint mechanisms.
AB - In the version of this article initially published, the annotation accompanying
ref. 47 ended with "though the modulation of microglia." The first word of this
phrase should have been "through." The error has been corrected in the HTML and
PDF versions of the article.
PMID- 29942042
TI - A decade in psychiatric GWAS research.
AB - After more than 10 years of accumulated efforts, genome-wide association studies
(GWAS) have led to many findings, most of which have been deposited into the GWAS
Catalog. Between GWAS's inception and March 2017, the GWAS Catalog has collected
2429 studies, 1818 phenotypes, and 28,462 associated SNPs. We reclassified the
psychology-related phenotypes into 217 reclassified phenotypes, which accounted
for 514 studies and 7052 SNPs. In total, 1223 of the SNPs reached genome-wide
significance. Of these, 147 were replicated for the same psychological trait in
different studies. Another 305 SNPs were replicated within one original study.
The SNPs rs2075650 and rs4420638 were linked to the most replications within a
single reclassified phenotype or very similar reclassified phenotypes; both were
associated with Alzheimer's disease (AD). Schizophrenia was associated with 74
within-phenotype SNPs reported in independents studies. Alzheimer's disease and
schizophrenia were both linked to some physical phenotypes, including cholesterol
and body mass index, through common GWAS signals. Alzheimer's disease also shared
risk SNPs with age-related phenotypes such as age-related macular degeneration
and longevity. Smoking-related SNPs were linked to lung cancer and respiratory
function. Alcohol-related SNPs were associated with cardiovascular and digestive
system phenotypes and disorders. Two separate studies also identified a shared
risk SNP for bipolar disorder and educational attainment. This review revealed a
list of reproducible SNPs worthy of future functional investigation.
Additionally, by identifying SNPs associated with multiple phenotypes, we
illustrated the importance of studying the relationships among phenotypes to
resolve the nature of their causal links. The insights within this review will
hopefully pave the way for future evidence-based genetic studies.
PMID- 29942044
TI - Pericytes in the renal vasculature: roles in health and disease.
AB - In the dense circulatory system of the kidney, as in all vascularized tissues,
pericytes enwrap capillaries and microvessels to regulate angiogenesis, stabilize
microvascular networks and control blood flow by vasoconstriction. Specialized
renal pericytes known as mesangial cells provide physical support to glomerular
capillaries, whereas a subset of juxtaglomerular arteriolar pericytes control the
local blood pressure in the glomerulus via contraction and influence systemic
blood pressure by secreting renin. Similar to pericytes from many other organs,
cultured human renal pericytes give rise to mesenchymal stem/stromal cells,
suggesting a role of perivascular cells in renal homeostasis and regeneration. On
the other hand, pericytes directly contribute to renal fibrosis, and mesangial
cells may have an essential role in the development of glomerulosclerosis and
other nephropathies. From their early emergence in the renal embryonic rudiment
to their distribution in diverse perivascular niches in the adult organ, we
review the anatomy and function of pericytes in the healthy and diseased kidney.
Many aspects of the ontogeny, specification and functional specialization of
renal pericytes remain elusive. The development of powerful models in the easily
accessible and genetically tractable zebrafish will help to uncover the multiple
facets of these cells.
PMID- 29942043
TI - Blunted endogenous opioid release following an oral dexamphetamine challenge in
abstinent alcohol-dependent individuals.
AB - Addiction has been proposed as a 'reward deficient' state, which is compensated
for with substance use. There is growing evidence of dysregulation in the opioid
system, which plays a key role in reward, underpinning addiction. Low levels of
endogenous opioids are implicated in vulnerability for developing alcohol
dependence (AD) and high mu-opioid receptor (MOR) availability in early
abstinence is associated with greater craving. This high MOR availability is
proposed to be the target of opioid antagonist medication to prevent relapse.
However, changes in endogenous opioid tone in AD are poorly characterised and are
important to understand as opioid antagonists do not help everyone with AD. We
used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET)
radioligand, to investigate endogenous opioid tone in AD for the first time. We
recruited 13 abstinent male AD and 15 control participants who underwent two
[11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral
dose of dexamphetamine to measure baseline MOR availability and endogenous opioid
release. We found significantly blunted dexamphetamine-induced opioid release in
5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD
compared with controls, but no significantly higher MOR availability AD
participants compared with HC in any region. This study is comparable to our
previous results of blunted dexamphetamine-induced opioid release in gambling
disorder, suggesting that this dysregulation in opioid tone is common to both
behavioural and substance addictions.
PMID- 29942045
TI - Molecular detection of small hive beetle Aethina tumida Murray (Coleoptera:
Nitidulidae): DNA barcoding and development of a real-time PCR assay.
AB - Small hive beetle (SHB), Aethina tumida can feed on honey, pollen and brood in
honey bee colonies. It was endemic to Africa, but since 1996 has been detected in
a number of countries worldwide, including Australia, Brazil, Canada, Italy,
Mexico, South Korea, Philippines and the USA where it has had economic effects on
local apiculture. To improve SHB identification, we obtained the first reference
sequences from the DNA barcoding 5' COI gene region for SHB and some species of
the family Nitidulidae associated with beehives. Phylogenetic analysis of SHB COI
sequences (3' COI) revealed two divergent lineages, with those from Australia and
USA being genetically different from the recent detection in Italy. Many
countries, including New Zealand, are currently free from SHB, and require a
rapid detection method for biosecurity. Here we present the development and
validation of a real-time PCR assay for detection of SHB. The assay showed high
specificity and sensitivity for detecting SHB, with no cross-reaction observed
with closely related species, such as A. concolor. The real-time PCR is
sensitive, detecting the target sequences up to 100 copies/uL. This assay should
prove a useful biosecurity tool for rapid detection of SHB worldwide.
PMID- 29942046
TI - It starts with TIRs.
PMID- 29942047
TI - Previsual symptoms of Xylella fastidiosa infection revealed in spectral plant
trait alterations.
AB - Plant pathogens cause significant losses to agricultural yields and increasingly
threaten food security1, ecosystem integrity and societies in general2-5. Xylella
fastidiosa is one of the most dangerous plant bacteria worldwide, causing several
diseases with profound impacts on agriculture and the environment6. Primarily
occurring in the Americas, its recent discovery in Asia and Europe demonstrates
that X. fastidiosa's geographic range has broadened considerably, positioning it
as a reemerging global threat that has caused socioeconomic and cultural
damage7,8. X. fastidiosa can infect more than 350 plant species worldwide9, and
early detection is critical for its eradication8. In this article, we show that
changes in plant functional traits retrieved from airborne imaging spectroscopy
and thermography can reveal X. fastidiosa infection in olive trees before
symptoms are visible. We obtained accuracies of disease detection, confirmed by
quantitative polymerase chain reaction, exceeding 80% when high-resolution
fluorescence quantified by three-dimensional simulations and thermal stress
indicators were coupled with photosynthetic traits sensitive to rapid pigment
dynamics and degradation. Moreover, we found that the visually asymptomatic trees
originally scored as affected by spectral plant-trait alterations, developed X.
fastidiosa symptoms at almost double the rate of the asymptomatic trees
classified as not affected by remote sensing. We demonstrate that spectral plant
trait alterations caused by X. fastidiosa infection are detectable previsually at
the landscape scale, a critical requirement to help eradicate some of the most
devastating plant diseases worldwide.
PMID- 29942048
TI - Rapid and reversible root growth inhibition by TIR1 auxin signalling.
AB - The phytohormone auxin is the information carrier in a plethora of developmental
and physiological processes in plants1. It has been firmly established that
canonical, nuclear auxin signalling acts through regulation of gene
transcription2. Here, we combined microfluidics, live imaging, genetic
engineering and computational modelling to reanalyse the classical case of root
growth inhibition3 by auxin. We show that Arabidopsis roots react to addition and
removal of auxin by extremely rapid adaptation of growth rate. This process
requires intracellular auxin perception but not transcriptional reprogramming.
The formation of the canonical TIR1/AFB-Aux/IAA co-receptor complex is required
for the growth regulation, hinting to a novel, non-transcriptional branch of this
signalling pathway. Our results challenge the current understanding of root
growth regulation by auxin and suggest another, presumably non-transcriptional,
signalling output of the canonical auxin pathway.
PMID- 29942049
TI - Improved identification of concordant and discordant gene expression signatures
using an updated rank-rank hypergeometric overlap approach.
AB - Recent advances in large-scale gene expression profiling necessitate concurrent
development of biostatistical approaches to reveal meaningful biological
relationships. Most analyses rely on significance thresholds for identifying
differentially expressed genes. We use an approach to compare gene expression
datasets using 'threshold-free' comparisons. Significance cut-offs to identify
genes shared between datasets may be too stringent and may miss concordant
patterns of gene expression with potential biological relevance. A threshold-free
approach gaining popularity in several research areas, including neuroscience, is
Rank-Rank Hypergeometric Overlap (RRHO). Genes are ranked by their p-value and
effect size direction, and ranked lists are compared to identify significantly
overlapping genes across a continuous significance gradient rather than at a
single arbitrary cut-off. We have updated the previous RRHO analysis by
accurately detecting overlap of genes changed in the same and opposite directions
between two datasets. Here, we use simulated and real data to show the drawbacks
of the previous algorithm as well as the utility of our new algorithm. For
example, we show the power of detecting discordant transcriptional patterns in
the postmortem brain of subjects with psychiatric disorders. The new R package,
RRHO2, offers a new, more intuitive visualization of concordant and discordant
gene overlap.
PMID- 29942051
TI - Who gets to be a PI?
PMID- 29942052
TI - Determining PI status.
PMID- 29942050
TI - Acute Heart Failure developed as worsening of Chronic Heart Failure is associated
with increased mortality compared to de novo cases.
AB - Acute heart failure (AHF) emerges either de novo or from worsening of chronic
heart failure (CHF). The aim of the present study was to evaluate the association
between worsening of CHF and mortality in AHF patients. Out of 152 included AHF
patients, 47 (30.9%) were de novo AHF patients and 105 (69%) were AHF patients
with worsening of CHF. The proportion dying in hospital (19.0% vs. 4.3%, p =
0.023) and within 3 months after hospitalization (36.6% vs. 6.7%, p < 0.001) was
significantly higher in AHF patients with worsening of CHF. Logistic regression
analyses also showed a significant positive association of AHF emerging as
worsening of CHF with hospital mortality [odds ratio (OR) and 95% confidence
interval (CI): 5.29 (1.46-34.10), p = 0.029] and 3-month mortality [8.09 (2.70
35.03), p = 0.001]. While the association with hospital mortality was no longer
significant after adjusting for comorbidities and clinical as well as laboratory
parameters known to be associated with mortality in heart failure patients, the
association with 3-month mortality remained significant. We conclude that
compared to de novo AHF, AHF evolved from worsening of CHF is a more severe
condition and is associated with increased mortality.
PMID- 29942053
TI - IACUC SOPs.
PMID- 29942054
TI - Modify the SOP.
PMID- 29942055
TI - July Updates: People and Places.
PMID- 29942056
TI - Getting personal with the "reproducibility crisis": interviews in the animal
research community.
PMID- 29942057
TI - A Word from APHIS and OLAW.
PMID- 29942058
TI - Circuit breakers.
PMID- 29942059
TI - Designing new biointerfaces with silicon.
PMID- 29942060
TI - A marker of sociality.
PMID- 29942061
TI - Epigenetic eyes.
PMID- 29942062
TI - Crikey! Croc MRIs.
PMID- 29942063
TI - Move freely with miniLFM.
PMID- 29942064
TI - DNA repair and longevity.
PMID- 29942065
TI - Sunny side up.
PMID- 29942066
TI - New bat genome and immunity.
PMID- 29942067
TI - Termites and aging.
PMID- 29942069
TI - In the name of reproducibility.
PMID- 29942070
TI - Where old players meet new regulators.
PMID- 29942071
TI - Getting to know the neighbors.
PMID- 29942072
TI - Genetic variability and ontogeny predict microbiome structure in a disease
challenged montane amphibian.
AB - Amphibian populations worldwide are at risk of extinction from infectious
diseases, including chytridiomycosis caused by the fungal pathogen
Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact
with Bd and can confer protective benefits to the host. The composition of the
microbiome itself is influenced by many environment- and host-related factors.
However, little is known about the interacting effects of host population
structure, genetic variation and developmental stage on microbiome composition
and Bd prevalence across multiple sites. Here we explore these questions in
Amietia hymenopus, a disease-affected frog in southern Africa. We use
microsatellite genotyping and 16S amplicon sequencing to show that the microbiome
associated with tadpole mouthparts is structured spatially, and is influenced by
host genotype and developmental stage. We observed strong genetic structure in
host populations based on rivers and geographic distances, but this did not
correspond to spatial patterns in microbiome composition. These results indicate
that demographic and host genetic factors affect microbiome composition within
sites, but different factors are responsible for host population structure and
microbiome structure at the between-site level. Our results help to elucidate
complex within- and among- population drivers of microbiome structure in
amphibian populations. That there is a genetic basis to microbiome composition in
amphibians could help to inform amphibian conservation efforts against infectious
diseases.
PMID- 29942074
TI - Experimental evidence for rapid genomic adaptation to a new niche in an adaptive
radiation.
AB - A substantial part of biodiversity is thought to have arisen from adaptive
radiations in which one lineage rapidly diversified into multiple lineages
specialized to many different niches. However, selection and drift reduce genetic
variation during adaptation to new niches and may thus prevent or slow down
further niche shifts. We tested whether rapid adaptation is still possible from a
highly derived ecotype in the adaptive radiation of threespine stickleback on the
Haida Gwaii archipelago, Western Canada. In a 19-year selection experiment, we
let giant sticklebacks from a large blackwater lake evolve in a small clearwater
pond without vertebrate predators. A total of 56 whole genomes from the
experiment and 26 natural populations revealed that adaptive genomic change was
rapid in many small genomic regions and encompassed 75% of the change between
12,000-year-old ecotypes. Genomic change was as fast as phenotypic change in
defence and trophic morphology, and both were largely parallel between the short
term selection experiment and long-term natural adaptive radiation. Our results
show that functionally relevant standing genetic variation can persist in derived
radiation members, allowing adaptive radiations to unfold very rapidly.
PMID- 29942073
TI - Macroevolution of gastric Helicobacter species unveils interspecies admixture and
time of divergence.
AB - Since the discovery of the human pathogen Helicobacter pylori, various other
Helicobacter species have been identified in the stomach of domesticated and wild
mammals. To better understand the evolutionary history of these ecologically
similar but genetically distinct species, we analyzed 108 gastric Helicobacter
genomes and included 54 enterohepatic Helicobacter genomes for comparison
purposes. An admixture analysis supported the presence of an ecological barrier,
preventing the genetic exchange between the gastric and enterohepatic
Helicobacter species, and unraveled many gene flow events within and across
species residing in the stomach. As pets can be colonized by multiple gastric
Helicobacter species, the genetic exchange between the canine and feline strains
was evident, with H. heilmannii and H. bizzozeronii showing the highest
interspecies recombination. An admixture between H. pylori (in particular, the
ancestral African strains), H. acinonychis from wild felines and H. cetorum from
marine mammals was also identified. Because these latter species do not share the
same host, this phenomenon is most likely a remaining signal of shared ancestry.
A reconstruction of the time of divergence of the gastric Helicobacter spp.
revealed that the domestic animal-related Helicobacter species evolved in
parallel with H. pylori and its two closest relatives (H. acinonychis and H.
cetorum), rather than together.
PMID- 29942077
TI - Unraveling the rewired network.
PMID- 29942075
TI - Multifunctional ferrofluid-infused surfaces with reconfigurable multiscale
topography.
AB - Developing adaptive materials with geometries that change in response to external
stimuli provides fundamental insights into the links between the physical forces
involved and the resultant morphologies and creates a foundation for
technologically relevant dynamic systems1,2. In particular, reconfigurable
surface topography as a means to control interfacial properties3 has recently
been explored using responsive gels4, shape-memory polymers5, liquid crystals6-8
and hybrid composites9-14, including magnetically active slippery surfaces12-14.
However, these designs exhibit a limited range of topographical changes and thus
a restricted scope of function. Here we introduce a hierarchical magneto
responsive composite surface, made by infiltrating a ferrofluid into a
microstructured matrix (termed ferrofluid-containing liquid-infused porous
surfaces, or FLIPS). We demonstrate various topographical reconfigurations at
multiple length scales and a broad range of associated emergent behaviours. An
applied magnetic-field gradient induces the movement of magnetic nanoparticles
suspended in the ferrofluid, which leads to microscale flow of the ferrofluid
first above and then within the microstructured surface. This redistribution
changes the initially smooth surface of the ferrofluid (which is immobilized by
the porous matrix through capillary forces) into various multiscale hierarchical
topographies shaped by the size, arrangement and orientation of the confining
microstructures in the magnetic field. We analyse the spatial and temporal
dynamics of these reconfigurations theoretically and experimentally as a function
of the balance between capillary and magnetic pressures15-19 and of the geometric
anisotropy of the FLIPS system. Several interesting functions at three different
length scales are demonstrated: self-assembly of colloidal particles at the
micrometre scale; regulated flow of liquid droplets at the millimetre scale; and
switchable adhesion and friction, liquid pumping and removal of biofilms at the
centimetre scale. We envision that FLIPS could be used as part of integrated
control systems for the manipulation and transport of matter, thermal management,
microfluidics and fouling-release materials.
PMID- 29942076
TI - Sarpagan bridge enzyme has substrate-controlled cyclization and aromatization
modes.
AB - Cyclization reactions that create complex polycyclic scaffolds are hallmarks of
alkaloid biosynthetic pathways. We present the discovery of three homologous
cytochrome P450s from three monoterpene indole alkaloid-producing plants
(Rauwolfia serpentina, Gelsemium sempervirens and Catharanthus roseus) that
provide entry into two distinct alkaloid classes, the sarpagans and the beta
carbolines. Our results highlight how a common enzymatic mechanism, guided by
related but structurally distinct substrates, leads to either cyclization or
aromatization.
PMID- 29942078
TI - Designing microbial consortia with defined social interactions.
AB - Designer microbial consortia are an emerging frontier in synthetic biology that
enable versatile microbiome engineering. However, the utilization of such
consortia is hindered by our limited capacity in rapidly creating ecosystems with
desired dynamics. Here we present the development of synthetic communities
through social interaction engineering that combines modular pathway
reconfiguration with model creation. Specifically, we created six two-strain
consortia, each possessing a unique mode of interaction, including commensalism,
amensalism, neutralism, cooperation, competition and predation. These consortia
follow distinct population dynamics with characteristics determined by the
underlying interaction modes. We showed that models derived from two-strain
consortia can be used to design three- and four-strain ecosystems with
predictable behaviors and further extended to provide insights into community
dynamics in space. This work sheds light on the organization of interacting
microbial species and provides a systematic framework-social interaction
programming-to guide the development of synthetic ecosystems for diverse
purposes.
PMID- 29942079
TI - Metabolic engineering of a carbapenem antibiotic synthesis pathway in Escherichia
coli.
AB - Carbapenems, a family of beta-lactam antibiotics, are among the most powerful
bactericidal compounds in clinical use. However, as rational engineering of
native carbapenem-producing microbes is not currently possible, the present
carbapenem supply relies upon total chemical synthesis of artificial carbapenem
derivatives. To enable access to the full diversity of natural carbapenems, we
have engineered production of a simple carbapenem antibiotic within Escherichia
coli. By increasing concentrations of precursor metabolites and identifying a
reducing cofactor of a bottleneck enzyme, we improved productivity by 60-fold
over the minimal pathway and surpassed reported titers obtained from carbapenem
producing Streptomyces species. We stabilized E. coli metabolism against
antibacterial effects of the carbapenem product by artificially inhibiting
membrane synthesis, which further increased antibiotic productivity. As all known
naturally occurring carbapenems are derived from a common intermediate, our
engineered strain provides a platform for biosynthesis of tailored carbapenem
derivatives in a genetically tractable and fast-growing species.
PMID- 29942080
TI - Cleavage of a carbon-fluorine bond by an engineered cysteine dioxygenase.
AB - Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by
regulating homeostatic levels of cysteine. Human CDO contains a post
translationally generated Cys93-Tyr157 cross-linked cofactor. Here, we
investigated this Cys-Tyr cross-linking by incorporating unnatural tyrosines in
place of Tyr157 via a genetic method. The catalytically active variants were
obtained with a thioether bond between Cys93 and the halogen-substituted Tyr157,
and we determined the crystal structures of both wild-type and engineered CDO
variants in the purely uncross-linked form and with a mature cofactor. Along with
mass spectrometry and 19F NMR, these data indicated that the enzyme could
catalyze oxidative C-F or C-Cl bond cleavage, resulting in a substantial
conformational change of both Cys93 and Tyr157 during cofactor assembly. These
findings provide insights into the mechanism of Cys-Tyr cofactor biogenesis and
may aid the development of bioinspired aromatic carbon-halogen bond activation.
PMID- 29942081
TI - Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast
cancer.
AB - Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of
breast cancers. However, clinical responses to drugs targeting this pathway have
been modest, possibly because of dynamic changes in cellular signaling that drive
resistance and limit drug efficacy. Using a quantitative chemoproteomics
approach, we mapped kinome dynamics in response to inhibitors of this pathway and
identified signaling changes that correlate with drug sensitivity. Maintenance of
AURKA after drug treatment was associated with resistance in breast cancer
models. Incomplete inhibition of AURKA was a common source of therapy failure,
and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237
were highly synergistic and durably suppressed mTOR signaling, resulting in
apoptosis and tumor regression in vivo. This signaling map identifies survival
factors whose presence limits the efficacy of targeted therapies and reveals new
drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway
inhibitors in breast cancer.
PMID- 29942082
TI - De novo variants in neurodevelopmental disorders with epilepsy.
AB - Epilepsy is a frequent feature of neurodevelopmental disorders (NDDs), but little
is known about genetic differences between NDDs with and without epilepsy. We
analyzed de novo variants (DNVs) in 6,753 parent-offspring trios ascertained to
have different NDDs. In the subset of 1,942 individuals with NDDs with epilepsy,
we identified 33 genes with a significant excess of DNVs, of which SNAP25 and
GABRB2 had previously only limited evidence of disease association. Joint
analysis of all individuals with NDDs also implicated CACNA1E as a novel disease
associated gene. Comparing NDDs with and without epilepsy, we found missense
DNVs, DNVs in specific genes, age of recruitment, and severity of intellectual
disability to be associated with epilepsy. We further demonstrate the extent to
which our results affect current genetic testing as well as treatment,
emphasizing the benefit of accurate genetic diagnosis in NDDs with epilepsy.
PMID- 29942083
TI - Leveraging molecular quantitative trait loci to understand the genetic
architecture of diseases and complex traits.
AB - There is increasing evidence that many risk loci found using genome-wide
association studies are molecular quantitative trait loci (QTLs). Here we
introduce a new set of functional annotations based on causal posterior
probabilities of fine-mapped molecular cis-QTLs, using data from the Genotype
Tissue Expression (GTEx) and BLUEPRINT consortia. We show that these annotations
are more strongly enriched for heritability (5.84* for eQTLs; P = 1.19 * 10-31)
across 41 diseases and complex traits than annotations containing all significant
molecular QTLs (1.80* for expression (e)QTLs). eQTL annotations obtained by meta
analyzing all GTEx tissues generally performed best, whereas tissue-specific eQTL
annotations produced stronger enrichments for blood- and brain-related diseases
and traits. eQTL annotations restricted to loss-of-function intolerant genes were
even more enriched for heritability (17.06*; P = 1.20 * 10-35). All molecular
QTLs except splicing QTLs remained significantly enriched in joint analysis,
indicating that each of these annotations is uniquely informative for disease and
complex trait architectures.
PMID- 29942084
TI - Defining endemic cholera at three levels of spatiotemporal resolution within
Bangladesh.
AB - Although much focus is placed on cholera epidemics, the greatest burden occurs in
settings in which cholera is endemic, including areas of South Asia, Africa and
now Haiti1,2. Dhaka, Bangladesh is a megacity that is hyper-endemic for cholera,
and experiences two regular seasonal outbreaks of cholera each year3. Despite
this, a detailed understanding of the diversity of Vibrio cholerae strains
circulating in this setting, and their relationships to annual outbreaks, has not
yet been obtained. Here we performed whole-genome sequencing of V. cholerae
across several levels of focus and scale, at the maximum possible resolution. We
analyzed bacterial isolates to define cholera dynamics at multiple levels,
ranging from infection within individuals, to disease dynamics at the household
level, to regional and intercontinental cholera transmission. Our analyses
provide a genomic framework for understanding cholera diversity and transmission
in an endemic setting.
PMID- 29942085
TI - Meta-analysis of genome-wide association studies for neuroticism in 449,484
individuals identifies novel genetic loci and pathways.
AB - Neuroticism is an important risk factor for psychiatric traits, including
depression1, anxiety2,3, and schizophrenia4-6. At the time of analysis, previous
genome-wide association studies7-12 (GWAS) reported 16 genomic loci associated to
neuroticism10-12. Here we conducted a large GWAS meta-analysis (n = 449,484) of
neuroticism and identified 136 independent genome-wide significant loci (124 new
at the time of analysis), which implicate 599 genes. Functional follow-up
analyses showed enrichment in several brain regions and involvement of specific
cell types, including dopaminergic neuroblasts (P = 3.49 * 10-8), medium spiny
neurons (P = 4.23 * 10-8), and serotonergic neurons (P = 1.37 * 10-7). Gene set
analyses implicated three specific pathways: neurogenesis (P = 4.43 * 10-9),
behavioral response to cocaine processes (P = 1.84 * 10-7), and axon part (P =
5.26 * 10-8). We show that neuroticism's genetic signal partly originates in two
genetically distinguishable subclusters13 ('depressed affect' and 'worry'),
suggesting distinct causal mechanisms for subtypes of individuals. Mendelian
randomization analysis showed unidirectional and bidirectional effects between
neuroticism and multiple psychiatric traits. These results enhance
neurobiological understanding of neuroticism and provide specific leads for
functional follow-up experiments.
PMID- 29942087
TI - Pan4Draft: A Computational Tool to Improve the Accuracy of Pan-Genomic Analysis
Using Draft Genomes.
AB - High-throughput sequencing technologies are a milestone in molecular biology for
facilitating great advances in genomics by enabling the deposit of large volumes
of biological data to public databases. The availability of such data has made
possible the comparative genomic analysis through pipelines, using the entire
gene repertoire of genomes. However, a large number of unfinished genomes exist
in public databases; their number is approximately 16-fold higher than the number
of complete genomes, which creates bias during comparative analyses. Therefore,
the present work proposes a new tool called Pan4Drafts, an automated pipeline for
pan-genomic analysis of draft prokaryotic genomes to maximize the representation
and accuracy of the gene repertoire of unfinished genomes by using reads from
sequencing data. Pan4Draft allows to perform comparative analyses using different
methodologies such as combining complete and draft genomes, using only draft
genomes or only complete genomes. Pan4Draft is available at
http://www.computationalbiology.ufpa.br/pan4drafts and the test dataset is
available at https://sourceforge.net/projects/pan4drafts .
PMID- 29942088
TI - A human anti-IL-2 antibody that potentiates regulatory T cells by a structure
based mechanism.
AB - Interleukin-2 (IL-2) has been shown to suppress immune pathologies by
preferentially expanding regulatory T cells (Tregs). However, this therapy has
been limited by off-target complications due to pathogenic cell expansion. Recent
efforts have been focused on developing a more selective IL-2. It is well
documented that certain anti-mouse IL-2 antibodies induce conformational changes
that result in selective targeting of Tregs. We report the generation of a fully
human anti-IL-2 antibody, F5111.2, that stabilizes IL-2 in a conformation that
results in the preferential STAT5 phosphorylation of Tregs in vitro and selective
expansion of Tregs in vivo. When complexed with human IL-2, F5111.2 induced
remission of type 1 diabetes in the NOD mouse model, reduced disease severity in
a model of experimental autoimmune encephalomyelitis and protected mice against
xenogeneic graft-versus-host disease. These results suggest that IL-2-F5111.2 may
provide an immunotherapy to treat autoimmune diseases and graft-versus-host
disease.
PMID- 29942089
TI - Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota
mediated metabolic health.
AB - The association between altered gut microbiota, intestinal permeability,
inflammation and cardiometabolic diseases is becoming increasingly clear but
remains poorly understood1,2. Indoleamine 2,3-dioxygenase is an enzyme induced in
many types of immune cells, including macrophages in response to inflammatory
stimuli, and catalyzes the degradation of tryptophan along the kynurenine
pathway. Indoleamine 2,3-dioxygenase activity is better known for its suppression
of effector T cell immunity and its activation of regulatory T cells3,4. However,
high indoleamine 2,3-dioxygenase activity predicts worse cardiovascular outcome5
9 and may promote atherosclerosis and vascular inflammation6, suggesting a more
complex role in chronic inflammatory settings. Indoleamine 2,3-dioxygenase
activity is also increased in obesity10-13, yet its role in metabolic disease is
still unexplored. Here, we show that obesity is associated with an increase of
intestinal indoleamine 2,3-dioxygenase activity, which shifts tryptophan
metabolism from indole derivative and interleukin-22 production toward kynurenine
production. Indoleamine 2,3-dioxygenase deletion or inhibition improves insulin
sensitivity, preserves the gut mucosal barrier, decreases endotoxemia and chronic
inflammation, and regulates lipid metabolism in liver and adipose tissues. These
beneficial effects are due to rewiring of tryptophan metabolism toward a
microbiota-dependent production of interleukin-22 and are abrogated after
treatment with a neutralizing anti-interleukin-22 antibody. In summary, we
identify an unexpected function of indoleamine 2,3-dioxygenase in the fine tuning
of intestinal tryptophan metabolism with major consequences on microbiota
dependent control of metabolic disease, which suggests indoleamine 2,3
dioxygenase as a potential therapeutic target.
PMID- 29942090
TI - Reply to 'F508del-CFTR is not corrected by thymosin alpha1'.
PMID- 29942086
TI - Genome-wide association meta-analysis in 269,867 individuals identifies new
genetic and functional links to intelligence.
AB - Intelligence is highly heritable1 and a major determinant of human health and
well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci
linked to variation in intelligence3-7, but much about its genetic underpinnings
remains to be discovered. Here, we present a large-scale genetic association
study of intelligence (n = 269,867), identifying 205 associated genomic loci (190
new) and 1,016 genes (939 new) via positional mapping, expression quantitative
trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based
association analysis. We find enrichment of genetic effects in conserved and
coding regions and associations with 146 nonsynonymous exonic variants.
Associated genes are strongly expressed in the brain, specifically in striatal
medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses
implicate pathways related to nervous system development and synaptic structure.
We confirm previous strong genetic correlations with multiple health-related
outcomes, and Mendelian randomization analysis results suggest protective effects
of intelligence for Alzheimer's disease and ADHD and bidirectional causation with
pleiotropic effects for schizophrenia. These results are a major step forward in
understanding the neurobiology of cognitive function as well as genetically
related neurological and psychiatric disorders.
PMID- 29942091
TI - Poly(GR) impairs protein translation and stress granule dynamics in C9orf72
associated frontotemporal dementia and amyotrophic lateral sclerosis.
AB - The major genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral
sclerosis (ALS) is a C9orf72 G4C2 repeat expansion1,2. Proposed mechanisms by
which the expansion causes c9FTD/ALS include toxicity from repeat-containing RNA
and from dipeptide repeat proteins translated from these transcripts. To
investigate the contribution of poly(GR) dipeptide repeat proteins to c9FTD/ALS
pathogenesis in a mammalian in vivo model, we generated mice that expressed GFP
(GR)100 in the brain. GFP-(GR)100 mice developed age-dependent neurodegeneration,
brain atrophy, and motor and memory deficits through the accumulation of diffuse,
cytoplasmic poly(GR). Poly(GR) co-localized with ribosomal subunits and the
translation initiation factor eIF3eta in GFP-(GR)100 mice and, of importance, in
c9FTD/ALS patients. Combined with the differential expression of ribosome
associated genes in GFP-(GR)100 mice, these findings demonstrate poly(GR)
mediated ribosomal distress. Indeed, poly(GR) inhibited canonical and non
canonical protein translation in HEK293T cells, and also induced the formation of
stress granules and delayed their disassembly. These data suggest that poly(GR)
contributes to c9FTD/ALS by impairing protein translation and stress granule
dynamics, consequently causing chronic cellular stress and preventing cells from
mounting an effective stress response. Decreasing poly(GR) and/or interrupting
interactions between poly(GR) and ribosomal and stress granule-associated
proteins may thus represent potential therapeutic strategies to restore
homeostasis.
PMID- 29942092
TI - Single-cell profiling of breast cancer T cells reveals a tissue-resident memory
subset associated with improved prognosis.
AB - The quantity of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is a
robust prognostic factor for improved patient survival, particularly in triple
negative and HER2-overexpressing BC subtypes1. Although T cells are the
predominant TIL population2, the relationship between quantitative and
qualitative differences in T cell subpopulations and patient prognosis remains
unknown. We performed single-cell RNA sequencing (scRNA-seq) of 6,311 T cells
isolated from human BCs and show that significant heterogeneity exists in the
infiltrating T cell population. We demonstrate that BCs with a high number of
TILs contained CD8+ T cells with features of tissue-resident memory T (TRM) cell
differentiation and that these CD8+ TRM cells expressed high levels of immune
checkpoint molecules and effector proteins. A CD8+ TRM gene signature developed
from the scRNA-seq data was significantly associated with improved patient
survival in early-stage triple-negative breast cancer (TNBC) and provided better
prognostication than CD8 expression alone. Our data suggest that CD8+ TRM cells
contribute to BC immunosurveillance and are the key targets of modulation by
immune checkpoint inhibition. Further understanding of the development,
maintenance and regulation of TRM cells will be crucial for successful
immunotherapeutic development in BC.
PMID- 29942093
TI - A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor
microenvironments.
AB - Intratumoral stimulatory dendritic cells (SDCs) play an important role in
stimulating cytotoxic T cells and driving immune responses against cancer.
Understanding the mechanisms that regulate their abundance in the tumor
microenvironment (TME) could unveil new therapeutic opportunities. We find that
in human melanoma, SDC abundance is associated with intratumoral expression of
the gene encoding the cytokine FLT3LG. FLT3LG is predominantly produced by
lymphocytes, notably natural killer (NK) cells in mouse and human tumors. NK
cells stably form conjugates with SDCs in the mouse TME, and genetic and cellular
ablation of NK cells in mice demonstrates their importance in positively
regulating SDC abundance in tumor through production of FLT3L. Although anti-PD-1
'checkpoint' immunotherapy for cancer largely targets T cells, we find that NK
cell frequency correlates with protective SDCs in human cancers, with patient
responsiveness to anti-PD-1 immunotherapy, and with increased overall survival.
Our studies reveal that innate immune SDCs and NK cells cluster together as an
excellent prognostic tool for T cell-directed immunotherapy and that these innate
cells are necessary for enhanced T cell tumor responses, suggesting this axis as
a target for new therapies.
PMID- 29942094
TI - Global characterization of T cells in non-small-cell lung cancer by single-cell
sequencing.
AB - Cancer immunotherapies have shown sustained clinical responses in treating non
small-cell lung cancer1-3, but efficacy varies and depends in part on the amount
and properties of tumor infiltrating lymphocytes4-6. To depict the baseline
landscape of the composition, lineage and functional states of tumor infiltrating
lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells
from 14 treatment-naive non-small-cell lung cancer patients. Combined expression
and T cell antigen receptor based lineage tracking revealed a significant
proportion of inter-tissue effector T cells with a highly migratory nature. As
well as tumor-infiltrating CD8+ T cells undergoing exhaustion, we observed two
clusters of cells exhibiting states preceding exhaustion, and a high ratio of
"pre-exhausted" to exhausted T cells was associated with better prognosis of lung
adenocarcinoma. Additionally, we observed further heterogeneity within the tumor
regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9,
an activation marker for antigen-specific Tregs. The gene signature of those
activated tumor Tregs, which included IL1R2, correlated with poor prognosis in
lung adenocarcinoma. Our study provides a new approach for patient stratification
and will help further understand the functional states and dynamics of T cells in
lung cancer.
PMID- 29942095
TI - F508del-CFTR is not corrected by thymosin alpha1.
PMID- 29942097
TI - Common variants in the GNL3 contribute to the increasing risk of knee
osteoarthritis in Han Chinese population.
AB - Osteoarthritis (OA) is a complex degenerative joint disorder, which is caused by
both environmental and genetic factors. Previous studies have indicated that the
GNL3 gene is associated with knee osteoarthritis (KOA) susceptibility in
Europeans; however, the exact molecular mechanism is still unclear. In the
present study, we investigated the potential genetic association of GNL3 with KOA
in a two-stage sample of 6,704 individuals from the Han Chinese population.
Subjects containing 1,052 KOA patients and 2,117 controls were considered the
discovery dataset, while subjects consisting of 1,173 KOA patients and 2,362
controls were utilized as the replication dataset. Single-SNP association,
imputation, and haplotypic association analyses were performed. The SNP of
rs11177 in GNL3 was identified to be significantly associated with KOA after
accounting for age, gender and BMI in both stages. The imputed SNP of rs6617 in
SPCS1 was found to be strongly associated with KOA risk, and the significant
association signal was confirmed in the replication stage. Moreover, a haplotype
based analysis also indicated a positive genetic effect of GNL3 on KOA
susceptibility. In summary, our results proved that GNL3 plays an important role
in the etiology of KOA, suggesting that GNL3 is a potential genetic modifier for
KOA development.
PMID- 29942096
TI - Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese
women.
AB - Hepatic steatosis is a multifactorial condition that is often observed in obese
patients and is a prelude to non-alcoholic fatty liver disease. Here, we combine
shotgun sequencing of fecal metagenomes with molecular phenomics (hepatic
transcriptome and plasma and urine metabolomes) in two well-characterized cohorts
of morbidly obese women recruited to the FLORINASH study. We reveal molecular
networks linking the gut microbiome and the host phenome to hepatic steatosis.
Patients with steatosis have low microbial gene richness and increased genetic
potential for the processing of dietary lipids and endotoxin biosynthesis
(notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic
and branched-chain amino acid metabolism. We demonstrated that fecal microbiota
transplants and chronic treatment with phenylacetic acid, a microbial product of
aromatic amino acid metabolism, successfully trigger steatosis and branched-chain
amino acid metabolism. Molecular phenomic signatures were predictive (area under
the curve = 87%) and consistent with the gut microbiome having an effect on the
steatosis phenome (>75% shared variation) and, therefore, actionable via
microbiome-based therapies.
PMID- 29942098
TI - The association of gestational age and birth weight with blood pressure among
children: a Chinese national study.
AB - Gestational age and birth weight are supposed to associate with childhood blood
pressure but remains unclear. This study aimed to investigate the association
between gestational age, birth weight, and blood pressure among Chinese children.
In all, 49 357 children aged 6-18 years were included from a nationwide survey in
China. Gestational age, birth weight, and socioeconomic data were collected by
questionnaires. Systolic (SBP) and diastolic (DBP) blood pressure were
objectively measured. The associations between birth measures and blood pressure
were examined by multivariable linear regression and logistic regression. The
prevalence of hypertension was 19.1%, 19.2%, and 21.0% in preterm, term, and post
term subgroups, and 20.1%, 19.1%, and 19.8% in low-, normal-, and high-birth
weight subgroups, respectively. Results showed significantly positive
associations of gestational age with SBP, DBP, SBP z-score, and DBP z-score in
the overall and term subgroup, but not in the preterm or post-term subgroup.
Birth weight was inversely related to SBP, DBP, SBP z-score, and DBP z-score
across the entire birth-weight spectrum, and the overall association was stronger
in girls than in boys. Similar associations were found in diffident age
subgroups. Children with high birth weight had decreased odds of hypertension (OR
0.84, 95% CI 0.77-0.92) after adjustment for covariates. Preterm birth increased
the risk of high SBP only in boys. This study suggested that gestational age was
positively associated with blood pressure only in term-born children. Birth
weight had a negative association with childhood blood pressure across the whole
range of birth weight.
PMID- 29942099
TI - ARE DISCOVERIES SPURIOUS? DISTRIBUTIONS OF MAXIMUM SPURIOUS CORRELATIONS AND
THEIR APPLICATIONS.
AB - Over the last two decades, many exciting variable selection methods have been
developed for finding a small group of covariates that are associated with the
response from a large pool. Can the discoveries by such data mining approaches be
spurious due to high dimensionality and limited sample size? Can our fundamental
assumptions on exogeneity of covariates needed for such variable selection be
validated with the data? To answer these questions, we need to derive the
distributions of the maximum spurious correlations given certain number of
predictors, namely, the distribution of the correlation of a response variable Y
with the best s linear combinations of p covariates X, even when X and Y are
independent. When the covariance matrix of X possesses the restricted eigenvalue
property, we derive such distributions for both finite s and diverging s, using
Gaussian approximation and empirical process techniques. However, such a
distribution depends on the unknown covariance matrix of X. Hence, we use the
multiplier bootstrap procedure to approximate the unknown distributions and
establish the consistency of such a simple bootstrap approach. The results are
further extended to the situation where residuals are from regularized fits. Our
approach is then applied to construct the upper confidence limit for the maximum
spurious correlation and testing exogeneity of covariates. The former provides a
baseline for guarding against false discoveries due to data mining and the latter
tests whether our fundamental assumptions for high-dimensional model selection
are statistically valid. Our techniques and results are illustrated by both
numerical examples and real data analysis.
PMID- 29942100
TI - A systematic review and meta-analysis of primary teeth caries studies in Gulf
Cooperation Council States.
AB - Objectives: The aim of the study was to evaluate the prevalence and severity of
dental caries in pre-school children in the Gulf Cooperation Council (GCC) area.
Methods: A search of literature was conducted to identify articles of dental
caries in primary dentitions published during the period from January 1st, 1992
to June 30th, 2016. PubMed, Google Scholar search, and hand searching of journals
was conducted to identify relevant articles. The search strategy employed both
dental subject headings and free-text terms. Results: Out of a total of 193
studies that fit the initial inclusion criteria, 159 studies were further
excluded. Only 34 studies were included in the systematic review and meta
analyses. The overall mean dmft in the primary teeth was 5.14 with prevalence of
80.9% in the GCC area. A high level of heterogeneity in the selected studies was
found as demonstrated by Q-value of 2538.501 (df = 21) and I2 value of 99.17%.
However, the funnel plots showed symmetrical shape at the bottom in both dmft and
prevalence studies indicating absence of publication bias, which was also
confirmed by insignificant result of Egger's regression statistical test (Egger's
test P = 0.179-0.358). Conclusion: Caries in the primary dentition in the GCC
States was high both in terms of mean dmft (5.14) and prevalence (80.95%).
PMID- 29942101
TI - Comparison of two surgical techniques in the treatment of multiple gingival
recessions sandwiched with a combination of A-PRF and L-PRF.
AB - Aim: The aim of this study is to compare semilunar vestibular incision technique
with pouch and tunnel technique in combination with A-PRF and L-PRF for treatment
of Miller's class I and II multiple gingival recessions. Method: This is a
randomized, controlled, double-blinded, split mouth study which consists of 16
systemically healthy patients with 96 sites and a mean age of 34.2 years, and
divided randomly into 2 groups, Group A consists of semilunar vestibular incision
technique sandwiched with A-PRF and L-PRF and Group B consists of Pouch and
tunnel technique sandwiched with A-PRF and L-PRF. Clinical parameters were
recorded at baseline, 3 months and 6 months which include plaque index, gingival
index, recession depth, recession width, clinical attachment loss and width of
keratinized tissue. Results: All the clinical parameters showed significantly
better levels for both the groups from baseline to 6 months. Semilunar vestibular
incision technique showed greater significance when compared to pouch and tunnel
technique from baseline to 6 months post operatively. Conclusion: The combination
of A-PRF and L-PRF with pouch and tunnel technique and semilunar vestibular
technique showed better outcome 6 months post operatively. Semilunar vestibular
incision technique showed promising results than pouch and tunnel technique for
the treatment of multiple gingival recessions.
PMID- 29942102
TI - Effectiveness of oral health education intervention among female primary school
children in Riyadh, Saudi Arabia.
AB - Objective: This study aimed to examine the effectiveness of oral health
intervention on the improvement in knowledge and self-reported oral health
behavior among 6-8 year old female primary school children in Riyadh, Saudi
Arabia. Materials and methods: The sample consisted of 1661 girls in primary
schools who are 6 to 8-year-olds (first, second and third graders). The
children's level of knowledge was assessed by a self-administered questionnaire
that was formulated for this specific age and divided into two parts; oral health
knowledge and self-reported oral health behavior. There were seven multiple
choice questions and one true/false question with five underlying parts in the
questionnaire which contained basic information about oral health knowledge, oral
hygiene practices and certain habits that affect teeth. The questionnaires were
distributed before and six weeks after implementation of the oral health
educational program to measure the level improvement of knowledge regarding oral
health among these children. Results: All the questions showed statistically
significant improvement in knowledge and self-reported behavior in the post
intervention group. There was a significant increase in the level of knowledge by
11.24% and level of self-reported behavior by 25% after intervention (P < 0.001).
The highest net change in the knowledge due to intervention was noted among third
graders (13.3%), whereas for self-reported oral health behavior, it was noted
among first graders (28.3%). Conclusion: The results of this study showed that an
easy-to-organize and inexpensive school-based intervention can, on a short-term
basis, be effective in improving the knowledge and self-reported oral health
behavior of children.
PMID- 29942103
TI - The effect of different finishing and polishing techniques on surface roughness
and gloss of two nanocomposites.
AB - Objectives: The aim of this in vitro study was to evaluate the effect of four
finishing and polishing protocols in Surface Roughness (Ra) and Surface Gloss
(Ga) of two different nanocomposites. Materials and Methods: In total, 50 disc
samples of a nanofilled resin and a nanohybrid resin were prepared. The samples
were assigned randomly to one of the five groups to which different polishing
protocols were applied. Analysis of surface roughness was performed using an
Atomic Force Microscope (AFM), with the gloss evaluated using a gloss
meter.Statistical evaluation of the results were analyzed using SPSS software,
based on one-way ANOVA parametric tests along with the Welch correction and the
Dunnett test for multiple comparisons of the tested protocols. Results: The
results evidence the significant influence of the applied Protocol Types and
Resin Types on Surface Roughness (Ra) and Surface Gloss (Ga). The multiple
comparisons between polishing systems highlight the contrast between the most
complex protocol, evidencing the lowest average Ra and the highest value Ga, and
control protocol, evidencing the highest average Ra and the lowest percentage Ga.
FiltekTM Supreme XT provided the best results in both Ra and Ga, in Protocol 4,
while Brilliant EverglowTM performed better in Protocols 2 and 3. Conclusions:
Both Ra and Ga are dependent on the type of protocol used, as protocol 4 evidence
a higher performance, depending also on the type of resins tested in the
research, as nanofilled resin provided the best results. Furthermore, the gloss
is influenced significantly by the surface roughness of the composite resin.
Clinical Relevance: In order to achieve excellent aesthetic appearance and high
durability of the direct restoration, it is important to select initially the
appropriate biomaterial for use and then to base preference for a polishing
technique on achieving perfect results in the surface texture.
PMID- 29942104
TI - Dental age estimation of Omani children using Demirjian's method.
AB - Dental age plays a significant role in forensic dentistry, orthodontics and
paediatric dentistry, as well as in general diagnosis and treatment planning.
Different methods have been developed to determine dental age. One of the most
commonly used methods is Demirjian's method, which was developed in 1973 from
research on a large number of French-Canadian children. It is based on the degree
of tooth mineralisation by examining the radiological appearance of the lower
mandibular left quadrant. The purpose of this study was to assess the dental age
of Omani children using Demirjian's method and evaluate the applicability of the
method in dental age estimation for Omani children. The sample consisted of 485
digital panoramic radiographs of children (264 males, 221 females) aged between
4.6 years and 16.5 years, and obtained from the records of the Military Dental
Centre in Oman. The data were analysed using SPSS. Paired t-tests, intraclass
correlation coefficients (ICC) and difference-against-mean plots were used to
compare the dental age calculated by Demirjian's method with chronological age. A
single examiner scored the radiographs, and intra-observer reliability was
evaluated using Cronbach's alpha on data from rescoring one out of every 20
radiographs. For boys, the mean difference between chronological age and dental
age for all age groups was 0.10 (95% CI -0.03 to 0.24). For girls, the mean
difference between chronological age and dental age for all age groups was 0.05
(95% CI -0.11 to 0.22). Difference-against-mean plots showed no evidence of
differential bias by age. For boys, the ICC was 0.896 (95% CI 0.869-0.917); for
girls, it was 0.886 (95% CI 0.854-0.911). Difference-against-mean plots for boys
(Fig. 1) and girls (Fig. 2) showed some evidence of differential bias by age. In
conclusion, the extent of the observed differences was sufficient for doubt to be
cast upon the utility of Demirjian's method for Oman, particularly when it is
considered that the method's most likely application would be in age
determination for minors in the workforce.
PMID- 29942105
TI - Prevalence of dental caries among male students aged 15-17 years in southern
Asir, Saudi Arabia.
AB - Background: Dental caries had been studied by several studies in Saudi Arabia
among different age groups and at various places. According to World Health
Organization (WHO), assessment of caries at 15 years of age is more meaningful.
The objective of this survey was to assess the prevalence of dental caries among
15-17-year teenage students in Abha, Saudi Arabia. Results of the present study
can be used as baseline data for future oral health interventions for the
population. Methods: A stratified cluster random sampling was followed in
selecting the students. The clinical data was collected using dentition status
component of WHO oral health assessment form 2013. Five investigators were
trained and calibrated with 20 subjects for two successive days (Cronbach's Alpha
= 0.91). Data was analyzed for descriptive statistics and Mann-Whitney U test was
applied to compare the DMFT scores. Results: Prevalence of dental caries among
the study population was found to be 72.9%. The DMFT scores were found to be
highest in the posteriors (90.7%). First permanent molar was the most common
tooth affected by dental caries in all quadrants. Conclusion: The present study
revealed that there is a high prevalence of dental caries among students aged 15
17 years in Abha, Saudi Arabia. Caries prevalence was highest in mandibular
posterior segments, however, it was lowest in mandibular anterior segments. There
is an urgent need for both preventive and curative dental health services in the
region. It is recommended that a coordinated school dental program may be
initiated in the area.
PMID- 29942106
TI - Color and translucency of finished and unfinished esthetic restorative materials
after staining and bleaching.
AB - Purpose: To evaluate the effect of staining and bleaching on color and
translucency of finished and unfinished nano-filled resin composite and giomer.
Materials and methods: Twenty specimens (ten finished + ten unfinished) were
fabricated from each material, then an initial color and translucency measurement
was taken. Specimens were stained in coffee for 48 h at 37 degrees C, rinsed and
dried. After which the second color and translucency measurement was taken. After
in-office bleaching with 40% H2O2 Opalescence boost, a third color and
translucency measurement was taken. CIE L* a* b* system was used for measuring
color change and translucency. Two-way ANOVA and paired t-test were used for
statistical analysis at P <= 0.05. Results: After staining, all specimens showed
clinically acceptable color change (DeltaE <= 3.3) with no significant
differences between groups. After bleaching, all specimens showed clinically
unacceptable color change (DeltaE > 3.3) and significant differences between
finished & polished and unfinished groups (P = 0.024). Nano-composites recorded
significantly higher translucency than giomer (P = 0.000) except after bleaching.
In addition, the translucency of unfinished groups were significantly higher than
finished & polished groups (P = 0.001). Conclusions: The tested materials
responded similarly to staining and bleaching. High concentration bleaching
increased color change and reduced translucency. Finishing & polishing
restorative materials improves their resistance to color change after bleaching,
but it adversely affects translucency.
PMID- 29942107
TI - Gender-specific oral health beliefs and behaviors among adult patients attending
King Abdulaziz Medical City in Riyadh.
AB - Aim: To explore variations in males' and females' oral health beliefs and
behaviors and to assess the influence of oral health beliefs on their related
behaviors within each gender. Materials and methods: A cross-sectional study was
designed to obtain information from patients attending outpatient clinics of King
Abdulaziz Medical City, Riyadh, Saudi Arabia. Of the 553 self-reported
questionnaires, 519 were filled comprising 251 males and 268 females. The
questionnaire consisted of two parts: six demographic questions and 25 questions
assessing oral health beliefs and behaviors. The statistical analysis was done
using frequency distribution and chi square tests. Results: Comparing males with
females, there was no significant gender difference in beliefs. However, when it
comes to behaviors, females were found to act more positively than males in many
assessed oral health aspects of the study. When comparing beliefs versus
behaviors towards the importance of oral health styles, a gap of 12-45% was noted
between those "who believe of oral health behaviors" and those "who actually
practiced them". Conclusions: The study presented valuable information about the
differences between beliefs and behaviors of Saudi population. It also indicated
that females in general, acted more positively toward oral health than males.
Health care providers might need to focus more on the improvement of oral health
behaviors and practices especially among males. The real reasons for lack of
behaviors need further investigation. Furthermore, oral health campaigns should
switch focus from people's education to oral health practices and actions.
PMID- 29942108
TI - Impact of dietary solvents on flexural properties of bulk-fill composites.
AB - Objective: This study investigated the effect of dietary solvents on flexural
strength and modulus of bulk-fill composites. Materials and methods: One
conventional composite (Filtek Z350 [FZ]), two bulk-fill composites (Filtek Bulk
fill [FB] and Tetric N Ceram [TN]) and a bulk-fill giomer (Beautifil-Bulk
Restorative [BB]) were evaluated. Specimens (12 * 2 * 2 mm) were fabricated using
customized stainless steel molds. Specimens were light-cured, removed from their
molds, finished, measured and randomly divided into six groups. The groups (n =
10) were conditioned in the following mediums for 7 days at 37 degrees C: air
(control), artificial saliva (SAGF), distilled water, 0.02 N citric acid,
heptane, 50% ethanol-water solution. After conditioning, the specimens were
rinsed, blotted dry, measured and subjected to flexural testing using a universal
testing machine. Representative SEM images of the intact surfaces were obtained
to appraise the degradation mechanism by dietary solvents. Data was subjected to
statistical analysis using ANOVA/Tukey's tests at significance level p < 0.05.
Results: Significant differences in flexural properties were observed between
materials and conditioning mediums. The highest flexural properties were usually
obtained with conditioning in air (control) or heptane. Exposure to aqueous
solutions generally reduced flexural properties of bulk-fill composites.
Conclusion: The effect of dietary solvents on flexural properties of bulk-fill
composites was material and medium dependent.
PMID- 29942109
TI - Educational environment as perceived by dental students at King Saud University.
AB - Objectives: Main objectives of the present study were to develop a baseline
information about dental students' perception of their educational environment at
the College of Dentistry, King Saud University (KSU) in Riyadh; and to
investigate the role of four different variables on the students' perception.
Methods: Dundee Ready Education Environment Measure (DREEM) questionnaire was
distributed among 497 undergraduate dental students, in the second week of the
first semester of the academic year, from second year students to interns
studying in the College of Dentistry of King Saud University (KSU). Results:
Response rate was 60.73%. Mean for the total DREEM scores was 108.42/200. DREEM
subscales mean were above 50% of the total score. DREEM overall score showed no
significant statistical difference among the four variables investigated, except
the academic year, where the second year students scored significantly higher
(118.36 +/- 15.8) compared to the interns (105 +/- 21.3). Conclusion: Students'
perception of educational environment in the KSU College of Dentistry was
satisfactory. However, several weak areas were identified which need some
attention and consideration.
PMID- 29942110
TI - Bilocular unicystic ameloblastoma of the mandible in a 9 yr old child - A
diagnostic and management dilemma.
AB - Unicystic ameloblastoma is a less encountered variant of the ameloblastoma that
usually presented as unicystic lesions of jaw occurring in 3rd and 4th decades of
life. It shows a typical ameloblastomatous epithelium lining the cyst cavity,
with or without variable tumor proliferations. The case presented here is of a 9
yr old boy who was referred to our center for the management of a large diffuse
swelling on the right side of the face. Clinical and radiologic evaluation showed
two interconnected cystic lesions in the right body and the symphyseal regions of
the mandible associated with impacted canines bilaterally. The initial
histopathology of both cystic spaces showed the lesion to be dentigerous cysts
and the results were reconfirmed in two other centers. A complete surgical
enucleation of this bilocular cyst was done sparing the impacted teeth. The
histopathologic examination of the post-operative specimen showed features of
Unicystic Ameloblastoma. The patient was followed up on a regular basis for more
than 3 years. There is no signs of recurrence and his latest radiographic
examinations shows good bone formation. The impacted teeth are erupting into
position. This case reports the difficulty in clinical diagnosis and the peculiar
bilocular presentation of unicystic ameloblastoma which was conservatively
managed by surgical enucleation of the complete lesion, sparing the dentition.
PMID- 29942111
TI - Feasibility of using allograft bone with resorbable collagen membrane for
alveolar ridge vertical defect augmentation for dental implant placement in
Patient with Aggressive Periodontitis: A case report.
AB - Purpose: This case report demonstrates the feasibility of using allograft bone
with a resorbable collagen membrane to correct an alveolar ridge defect and
achieve a highly esthetic restoration. Case presentation: A 30-year-old woman
with generalized aggressive periodontitis and advanced periodontal vertical bone
loss in periodontally hopeless upper left right premolar which required a fixed
restoration. A staged surgical strategy was devised. First, a resorbable collagen
membrane and allograft bone grafts were used to guide bone regeneration in the
vertical alveolar defect. After 6 months, complete bone regeneration was achieved
and the dental implants were submerged in the bone. Three months later, the
implants were exposed and subsequently restored with a crown. Conclusion: The
vertical guided bone regeneration strategy of using allograft bone and a
resorbable collagen membrane has the potential to eliminate the need for
additional procedures, which are required with non-resorbable membranes, sinus
lift procedures, and extensive block graft procedures.
PMID- 29942112
TI - Dentofacial characteristics in a child with Meier-Gorlin syndrome: A rare case
report.
AB - Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized
by the triad of microtia, absent or small patellae and short stature. The other
associated clinical features may include developmental delay, congenital
pulmonary emphysema, gastro-esophageal reflux, urogenital anomalies, such as
cryptorchidism and feeding problems. The facial characteristics during childhood
are typical, comprising of a small mouth with full lips and
micrognathia/retrognathia. The condition is rare affecting about one to nine
individuals per million. Mutation in the genes of pre-replication complex
involved in DNA-replication is detected in the majority of patients. This impedes
the cellular proliferation resulting in a reduction of total cell number and
thereby retardation of overall growth. This case report describe the typical
dentofacial characteristics in a 5 years old child affected with Meier-Gorlin
syndrome along with other associated anomalies and a multidisciplinary approach
for their management.
PMID- 29942113
TI - Orthodontic extrusion of Ellis Class VIII fracture of maxillary lateral incisor -
The sling shot method.
AB - The aim of this paper is to evaluate the efficacy of forced extrusion using the
sling shot elastic. A 21 year adult patient reported with an Ellis Class VIII
fracture of the maxillary right lateral incisor. Root canal treatment followed by
a fiber reinforced composite post was placed and core build up was done. A metal
button was bonded to the tooth. Begg brackets were placed from the second
premolar on one side to the second premolar on the opposite side. 0.016" * 0.025"
stainless steel was placed in ribbon mode. The ligature wire was placed as a
sling shot from the button on the fractured tooth to the two adjacent teeth. 4 mm
of extrusion was achieved and there was no evidence of root resorption. Forced
extrusion was achieved in four months. The sling shot method is a very effective
method of ligation. Light forces are delivered over a long duration with
definitive results as compared to the inconsistent force delivery with
conventional extrusion mechanics.
PMID- 29942114
TI - Argus II retinal prosthesis system: a review of patient selection criteria,
surgical considerations, and post-operative outcomes.
AB - Retinitis pigmentosa (RP) is a group of heterogeneous inherited retinal
degenerative disorders characterized by progressive rod and cone dysfunction and
ensuing photoreceptor loss. Many patients suffer from legal blindness by their
40s or 50s. Artificial vision is considered once patients have lost all vision to
the point of bare light perception or no light perception. The Argus II retinal
prosthesis system is one such artificial vision device approved for patients with
RP. This review focuses on the factors important for patient selection. Careful
pre-operative screening, counseling, and management of patient expectations are
critical for the successful implantation and visual rehabilitation of patients
with the Argus II device.
PMID- 29942115
TI - Annatto-derived tocotrienol stimulates osteogenic activity in preosteoblastic
MC3T3-E1 cells: a temporal sequential study.
AB - Purpose: Annatto-derived tocotrienol (AnTT) has been shown to improve bone
formation in animal models of osteoporosis. However, detailed studies of the
effects of AnTT on preosteoblastic cells were limited. This study was conducted
to investigate the osteogenic effect of AnTT on preosteoblast MC3T3-E1 cells in a
time-dependent manner. Materials and methods: Murine MC3T3-E1 preosteoblastic
cells were cultured in the different concentrations of AnTT (0.001-1 ug/mL) up to
24 days. Expression of osteoblastic differentiation markers was measured by qPCR
(osterix [OSX], collagen 1 alpha 1 [COL1alpha1], alkaline phosphatase [ALP], and
osteocalcin [OCN]) and by fluorometric assay for ALP activity. Detection of
collagen and mineralized nodules was done via Direct Red staining and Alizarin
Red staining, respectively. Results: The results showed that osteoblastic
differentiation-related genes, such as OSX, COL1alpha1, ALP, and OCN, were
significantly increased in the AnTT-treated groups compared to the vehicle group
in a time-dependent manner (P<0.05). Type 1 collagen level was increased from day
3 to day 15 in the AnTT-treated groups, while ALP activity was increased from day
9 to day 21 in the AnTT-treated groups (P<0.05). Enhanced mineralization was
observed in the AnTT-treated groups via increasing Alizarin Red staining from day
3 to day 21 (P<0.05). Conclusion: Our results suggest that AnTT enhances the
osteogenic activity by promoting the bone formation-related genes and proteins in
a temporal and sequential manner.
PMID- 29942116
TI - Cyclooxygenase inhibitors potentiate receptor tyrosine kinase therapies in
bladder cancer cells in vitro.
AB - Purpose: Receptor tyrosine kinase inhibitors (RTKIs) are used as targeted
therapies for patients diagnosed with cancer with highly expressed receptor
tyrosine kinases (RTKs), including the platelet-derived growth factor receptor
(PDGFR) and c-Kit receptor. Resistance to targeted therapies is partially due to
the activation of alternative pro-survival signaling pathways, including
cyclooxygenase (COX)-2. In this study, we validated the effects of two RTKIs,
axitinib and AB1010, in combination with COX inhibitors on the V-akt murine
thymoma oncogene homolog 1 (Akt) and COX-2 signaling pathways in bladder cancer
cells. Methods: The expression of several RTKs and their downstream signaling
targets was analyzed by Western blot (WB) analysis in human and canine bladder
transitional cell carcinoma (TCC) cell lines. The effects of RTKIs and COX
inhibitors in bladder TCC cells were assessed by MTS for cell viability, by
Caspase-3/7 and Annexin V assay for apoptosis, by WB analysis for detection of
COX-2 and Akt signaling pathways, and by enzyme-linked immunosorbent assay for
detection of prostaglandin E2 (PGE2) levels. Results: All tested TCC cells
expressed the c-Kit and PDGFRalpha receptors, except human 5637 cells that had
low RTKs expression. In addition, all tested cells expressed COX-1, COX-2, Akt,
extracellular signal regulated kinases 1/2, and nuclear factor kappa-light-chain
enhance of activated B cells proteins, except human UM-UC-3 cells, where no COX-2
expression was detected by WB analysis. Both RTKIs inhibited cell viability and
increased apoptosis in a dose-dependent manner in tested bladder TCC cells, which
positively correlated with their expression levels of the PDGFRalpha and c-Kit
receptors. RTKIs increased the expression of COX-2 in h-5637 and K9TCC#1Lillie
cells. Co-treatment of indomethacin inhibited AB1010-induced COX-2 expression
leading to an additive effect in inhibition of cell viability and PGE2 production
in tested TCC cells. Conclusion: Co-treatment of RTKIs with indomethacin
inhibited cell viability and AB1010-induced COX-2 expression resulting in
decreased PGE2 production in tested TCC cells. Thus, COX inhibition may further
potentiate RTKIs therapies in bladder cancer.
PMID- 29942117
TI - Icariside II ameliorates endothelial dysfunction by regulating the MAPK pathway
via miR-126/SPRED1 in diabetic human cavernous endothelial cells.
AB - Aim: The aim of the study was to investigate whether miR-126, a regulator of MAPK
signaling via targeting sprouty-related EVH1 domain-containing protein 1 (SPRED1)
mRNA, is involved in the process by which icariside II (ICA II) ameliorates
endothelial dysfunction in human cavernous endothelial cells (hCECs) exposed to a
diabetic-like environment. Materials and methods: Primary hCECs were isolated and
divided into three groups, normal control, diabetes mellitus (DM), and DM treated
with ICA II. The cell proliferation and migration abilities of the hCECs were
examined. The expression levels of endothelial-related microRNAs and relative
target mRNAs (SPRED1, phosphoinositol-3 kinase regulatory subunit 2, and vascular
cell adhesion molecule 1) of miR-126 were determined by real-time PCR. The
protein expression of endothelial nitric oxide synthase, receptor for advanced
glycation end products, and SPRED1, and MAPK signaling activities was determined
by Western blot analysis. In addition, miR-126 agomir and antagomir were used for
transfection into hCECs to further testify the association between miR-126 and
its targeting mRNA SPRED1. Results: hCECs induced with glucose plus advanced
glycation end product-BSA showed a significant decrease in endothelial nitric
oxide synthase, Ki-67, and miR-126 expression; a downregulated cell migration
ability and an increased receptor for advanced glycation end products level. ICA
II could partially reverse these changes. SPRED1 mRNA showed a contrary tendency
with the miR-126-3p changes. The level of SPRED1 protein increased after the
hCECs were induced with glucose plus advanced glycation end product-BSA, and ICA
II could rescue its aberrant expression. In addition, the MAPK pathway was
downregulated in the hCECs under diabetic conditions, and ICA II could partially
enhance its signaling activities. miR-126 was obviously downregulated, and SPRED1
was accordingly upregulated after miR-126 antagomir transfection, while ICA II
treatment could recover the expressions of both miR-126 and SPRED1. Moreover, the
upregulation of miR-126 and the inhibition of SPRED1 were noticed in the diabetic
hCECs by further transfection with miR-126 agomir. Conclusion: ICA II could
ameliorate endothelial dysfunction by regulating the MAPK pathway via miR
126/SPRED1 in hCECs exposed to a diabetic-like environment, and ICA II might be a
protective agent for endothelial function in diabetic ED.
PMID- 29942118
TI - Evaluating pulmonary function, aerobic capacity, and pediatric quality of life
following a 10-week aerobic exercise training in school-aged asthmatics: a
randomized controlled trial.
AB - Background: It has been documented that aerobic exercise may increase pulmonary
functions and aerobic capacity, but limited data has evaluated a child's
satisfaction and pediatric quality of life (PQoL) with exercise training.
Objectives: This study aimed to investigate the effects of moderate-intensity
exercise training on asthmatic school-aged children. Subjects and methods: This
study included 38 school-aged children with asthma (23 males and 15 females) aged
between 8-12 years. They were randomly assigned to two groups, aerobic exercise
(AE) and conventional treatment (Con ttt) groups. The AE group received a program
of moderate-intensity aerobic exercise for 10 weeks with asthma medications and
the Con ttt group received only asthma medications without exercise intervention.
A home respiratory exercise was recommended for the two groups. Aerobic capacity
was investigated using maximal oxygen uptake (VO2max), 6-minute walk test (6MWT),
and fatigue index. PQoL was evaluated using Pediatric Quality of Life
Questionnaire (PQoLQ). Also, pulmonary function tests were performed, and the
results recorded. Results: The findings of this study showed significant
improvements in pulmonary functions and VO2max in the two groups; however, this
improvement was significantly higher in the AE group than in the Con ttt group
(p<0.05). The 6MWT and fatigue index improved in the AE group (p<0.05) but not in
the Con ttt group (p>0.05). All dimensions of PQoL significantly improved in the
AE group (p<0.05), but there was no significant improvement in the Con ttt group
after the 10-week intervention period (p>0.05). Conclusion: Ten weeks of physical
exercise had beneficial effects on pulmonary functions, aerobic capacity, and
PQoL in school-aged children with asthma. Effort and awareness should be
dedicated to encouraging the active lifestyle among different populations,
especially asthmatic children.
PMID- 29942119
TI - Chronic myeloid leukemia patients and treatment-free remission attitudes: a
multicenter survey.
AB - Background: Treatment-free remission (TFR) is becoming an essential goal for
chronic myeloid leukemia (CML) patients in clinical practice. Few studies have
emphasized patient attitudes or preferences about discontinuing tyrosine kinase
inhibitors treatment. This study aimed to evaluate the characteristics of Chinese
CML patients and their views and perspectives on TFR. Methods: A total of 329 CML
patients participated in this multicenter, questionnaire-based, standardized,
semi-structured, interview-guided, open-ended, cross-sectional study. Information
about demographics, diagnosis information, treatment history, quality of life
(QoL), and TFR preference was collected. Results: The adherence rate was 50%
(N=163) and sex dependent (males, OR=2.24, 95% CI=1.40-3.58). Physical activity,
symptom burden, mood impact, and daily impact were found to be better among
adherent patients. Thirty-four percent of the patients were willing to attempt
TFR positively. The reasons for preferring TFR were due to side effects (56%)
followed by high cost (52%), inconvenience (42%), and pregnancy need (41%).
Multivariate analysis indicated that patients who were younger (OR=0.96, 95%
CI=0.94-0.99) with shorter disease duration (OR=0.90, 95% CI=0.82-0.98) and
higher disease symptom burden (OR=1.08, 95% CI=0.98-1.21) were more likely
positive about TFR. Conclusion: Patients who were younger with shorter disease
duration and higher disease symptom burden were more likely to try TFR. They
expressed several perceived noncost factors of TFR. Our data may help promote the
management of CML and designing of clinical trials for TFR in some developed
regions of China.
PMID- 29942120
TI - Ginkgo biloba extract EGb 761(r) alleviates neurosensory symptoms in patients
with dementia: a meta-analysis of treatment effects on tinnitus and dizziness in
randomized, placebo-controlled trials.
AB - Background: Tinnitus and dizziness are frequent in old age and often seen as
concomitant symptoms in patients with dementia. In earlier clinical trials,
Ginkgo biloba extract EGb 761(r) was found to alleviate tinnitus and dizziness in
elderly patients. Consequently, a meta-analysis was conducted to evaluate the
effects of EGb 761(r) at a daily dose of 240 mg on tinnitus and dizziness
associated with dementia. Methods: Randomized, placebo-controlled clinical trials
of G. biloba extract EGb 761(r) identified by a systematic database search were
included in a meta-analysis if they met all of the following selection criteria:
1) diagnosis of dementia according to generally accepted criteria, 2) treatment
period of at least 20 weeks, 3) outcome measures covering at least two of the
three conventional domains of assessment, 4) presence and severity of dizziness
and tinnitus were assessed, and 5) assessment was done before and after
randomized treatment. Results: Five trials that met the inclusion criteria were
included in the meta-analysis. The risk of bias was judged as low, with Jadad
scores of 3 and 5. In all trials, 11-point box scales were used to assess the
severity of tinnitus and dizziness. Overall, EGb 761(r) was superior to placebo,
with weighted mean differences for change from baseline, calculated in meta
analyses using random effects models, of -1.06 (95% CI: -1.77, -0.36) for
tinnitus (p = 0.003) and -0.77 (95% CI: -1.44, -0.09) for dizziness (p = 0.03).
Conclusion: Our findings support the notion that EGb 761(r) is also effective in
alleviating concomitant neurosensory symptoms in patients with dementia.
PMID- 29942121
TI - Prevalence of multimorbidity in subjects aged >=60 years in a developing country.
AB - Background: Aging is one of the most prominent features in recent population
dynamics around the world. As populations age, the prevalence of simultaneous
chronic diseases increases, which is known as multimorbidity. Objective: The aim
of the present study was to determine the prevalence of multimorbidity and
associated factors in a sample of elderly Mexican subjects. Materials and
methods: A cross-sectional descriptive study was performed on a convenience
sample of 139 subjects aged >=60 years. The dependent variable was the
multimorbidity diagnosis performed by a physician, which was categorized as 0 for
subjects with no chronic disease or only 1 disease and 1 for subjects with 2 or
more chronic diseases. Questionnaires were used to collect the information on the
different variables. A statistical analysis was performed in Stata 11.0. Results:
The mean age was 79.06+/-9.78 years, and 69.1% of the subjects were women. A
total of 69.1% (95% confidence interval =61.3-76.8) reported at least 1
morbidity. The mean morbidity by subject was 1.04+/-1.90. Cardiovascular diseases
(25.9%), hypertension (20.1%), musculoskeletal disorders (19.4%), and diabetes
(13.7%) were the most frequently reported conditions. The prevalence of
multimorbidity (2 or more diseases) was 27.3% (95% confidence interval =19.8
34.8). No significant differences were observed in the independent variables.
Conclusion: In conclusion, the prevalence of multimorbidity in this sample of
elderly Mexican subjects was relatively low. The distribution across the included
variables was not significantly different. Interventions focused on the health
care of older adults with multimorbidity should pay special attention to
cardiovascular diseases, hypertension, and musculoskeletal disorders.
PMID- 29942122
TI - Alternative definitions of chronic bronchitis and their correlation with CT
parameters.
AB - Introduction: Phenotyping of chronic bronchitis (CB) using COPD assessment tool
(CAT) scores and St George's Respiratory Questionnaire (SGRQ) has rarely been
attempted. The present study defined CB using CAT 1 and 2 scores and the
questions on the severity of cough and sputum from the SGRQ. Furthermore, the
predictability of CT parameters was also assessed for each CB definition.
Materials and methods: Patients enrolled in the Korean Obstructive Lung Disease
study from June 2005 to October 2015 were evaluated for this study. The patients
were spirometrically diagnosed with COPD and had a smoking history of >10 pack
years. Volumetric CT scans were performed for each patient upon enrollment in the
cohort. Two definitions of CB using CAT 1/2 scores and SGRQ questions were used
to phenotype CB among the study patients. Receiver operating characteristic curve
analysis was performed to estimate the predictability of CT parameters for the CB
phenotypes. Results: Using CAT 1/2 scores, 57 of 279 (20.4%) patients had CB, and
178 of 573 (31.1%) had CB when the SGRQ questions were used to phenotype it.
Total CAT and SGRQ scores were significantly higher in the CB group than those in
the non-CB group for both definitions of CB. Forced expiratory volume in 1 second
was lower for both CAT-defined and SGRQ-defined CB than that in the non-CB group.
Mean wall thickness was significantly higher for both CB groups than in the non
CB group. Expiratory lung volume was higher and mean lung density was
significantly lower for the SGRQ-defined CB group than non-CB group. Conclusion:
The 2 CB definitions using CAT scores and the SGRQ questions correlated with
associated CT airway parameters. SGRQ-defined CB better reflected the
accompaniment of small airway obstruction when compared with CAT-defined CB.
PMID- 29942123
TI - Can CAPTURE be used to identify undiagnosed patients with mild-to-moderate COPD
likely to benefit from treatment?
AB - Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory
Disease and Exacerbation Risk (CAPTURETM) uses five questions and peak expiratory
flow (PEF) thresholds (males <=350 L/min; females <=250 L/min) to identify
patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity
(FVC) <0.70 and FEV1 <60% predicted or exacerbation risk requiring further
evaluation for COPD. This study tested CAPTURE's ability to identify symptomatic
patients with mild-to-moderate COPD (FEV1 60%-80% predicted) who may also benefit
from diagnosis and treatment. Methods: Data from the CAPTURE development study
were used to test its sensitivity (SN) and specificity (SP) differentiating mild
to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all
COPD cases (mild to severe; n=259) from those without COPD (n=87) were also
estimated. The modified Medical Research Council (mMRC) dyspnea scale and COPD
Assessment Test (CATTM) were used to evaluate symptoms and health status.
Clinical Trial Registration: NCT01880177,
https://ClinicalTrials.gov/ct2/show/NCT01880177?term=NCT01880177&rank=1. Results:
Mean age (+SD): 61 (+10.5) years; 41% male. COPD: FEV1/FVC=0.60 (+0.1), FEV1%
predicted=74% (+12.4). SN and SP for differentiating mild-to-moderate and non
COPD patients (n=160): Questionnaire: 83.6%, 67.8%; PEF (<=450 L/min; <=350
L/min): 83.6%, 66.7%; CAPTURE (Questionnaire+PEF): 71.2%, 83.9%. COPD patients
whose CAPTURE results suggested that diagnostic evaluation was warranted (n=52)
were more likely to be symptomatic than patients whose results did not (n=21)
(mMRC >2: 37% vs 5%, p<0.01; CAT>10: 86% vs 57%, p<0.01). CAPTURE differentiated
COPD from no COPD (n=346): SN: 88.0%, SP: 83.9%. Conclusion: CAPTURE (450/350)
may be useful for identifying symptomatic patients with mild-to-moderate airflow
obstruction in need of diagnostic evaluation for COPD.
PMID- 29942124
TI - Comorbidities, mortality, and management of chronic obstructive pulmonary disease
patients who required admissions to public hospitals in Hong Kong - computerized
data collection and analysis.
AB - Background: COPD is a common cause for hospital admission. Conventional studies
of the epidemiology of COPD involved large patient number and immense resources
and were difficult to be repeated. The present study aimed at assessing the
utilization of a computerized data management system in the collection and
analysis of the epidemiological and clinical data of a large COPD cohort in Hong
Kong (HK). Patients and methods: It was a computerized, multicenter,
retrospective review of the characteristics of patients discharged from medical
departments of the 16 participating hospitals with the primary discharge
diagnosis of COPD in 1 year (2012). Comparison was made between the different
subgroups in the use of medications, ventilatory support, and other health care
resources. The mortality of the subjects in different subgroups was traced up to
December 31, 2014. The top 10 causes of death were analyzed. Results: In total,
9,776 subjects (82.6% men, mean age = 78 years) were identified. Of the 1,918
subjects with lung function coding, 85 (4.4%), 488 (25.5%), 808 (42.1%), and 537
(28.0%) subjects had the Global Initiative for Chronic Obstructive Lung Disease
(GOLD) 1, 2, 3, and 4 classes, respectively. Patients with higher GOLD classes
had higher number of hospital admissions, longer hospital stay, increased usage
of noninvasive mechanical ventilation (NIV), combinations of long-acting
bronchodilators, and higher mortality. Of the 9,776 subjects, 2,278 (23.3%)
received NIV, but invasive mechanical ventilation was uncommon (134 of 9,776
subjects [1.4%]); 4,427 (45.3%) subjects had died by the end of 2014. The top
causes of death were COPD, pneumonia, lung cancer, and other malignancies.
Conclusion: Patients admitted to hospitals for COPD in HK had significant
comorbidities, mortality, and imposed heavy burden on health care resources. It
is possible to collect and analyze data of a large COPD cohort through a
computerized system. Suboptimal coding of lung function results was observed, and
underutilization of long-acting bronchodilators was common.
PMID- 29942125
TI - Prediction models for the development of COPD: a systematic review.
AB - Early identification of people at risk of developing COPD is crucial for
implementing preventive strategies. We aimed to systematically review and assess
the performance of all published models that predicted development of COPD. A
search was conducted to identify studies that developed a prediction model for
COPD development. The Checklist for Critical Appraisal and Data Extraction for
Systematic Reviews of Prediction Modelling Studies was followed when extracting
data and appraising the selected studies. Of the 4,481 records identified, 30
articles were selected for full-text review, and only four of these were eligible
to be included in the review. The only consistent predictor across all four
models was a measure of smoking. Sex and age were used in most models; however,
other factors varied widely. Two of the models had good ability to discriminate
between people who were correctly or incorrectly classified as at risk of
developing COPD. Overall none of the models were particularly useful in
accurately predicting future risk of COPD, nor were they good at ruling out
future risk of COPD. Further studies are needed to develop new prediction models
and robustly validate them in external cohorts.
PMID- 29942126
TI - Significance of prolonged QTc in acute exacerbations of COPD requiring
hospitalization.
AB - Background: A prolonged QT interval is associated with increased risk of Torsade
de Pointes and cardiovascular death. The prevalence and clinical relevance of QT
prolongation in acute exacerbations of COPD (AECOPD), with high risk for cardiac
morbidity and mortality, is currently unclear. Methods: A dual cross-sectional
study strategy was therefore designed. A retrospective study evaluated 140
patients with an AECOPD requiring hospitalization, half of which had prolonged
QTc on the admission ECG. Univariate and multivariate analyses were conducted to
determine associated factors; Kaplan-Meier and Cox regression analyses to assess
prognostic significance. A prospective study evaluated 180 pulmonary patients
with acute respiratory problems requiring hospitalization, to determine whether a
prolonged QTc at admission represents an AECOPD-specific finding and to
investigate the change in QTc-duration during hospitalization. Results:
Retrospectively, hypokalemia, cardiac troponin T and conductance abnormalities on
ECG were significantly and independently associated with QTc prolongation. A
prolonged QTc was associated with increased all-cause mortality (HR 2.698 (95% CI
1.032-7.055), p=0.043), however, this association was no longer significant when
corrected for age, FEV1 and cardiac troponin T. Prospectively, QTc prolongation
was observed in 1/3 of the patients diagnosed with either an AECOPD, lung cancer,
pulmonary infection or miscellaneous acute pulmonary disease, and was not more
prevalent in AECOPD. The QTc-duration decreased significantly during
hospitalization in patients with and without COPD. Conclusion: A prolonged QTc is
a marker of underlying cardiovascular disease during an AECOPD. It is not COPD
specific, but a common finding during the acute phase of a pulmonary disease
requiring urgent hospital admission.
PMID- 29942127
TI - Satisfaction, preference and error occurrence of three dry powder inhalers as
assessed by a cohort naive to inhaler operation.
AB - Background: Inhaled medication is central to the treatment of COPD. Various types
of inhaler devices, which directly deliver medication to the lung, have been
developed. However, patients often exhibit incorrect techniques of inhaler usage.
Effectiveness of therapy may be affected by the ease of device usage, size,
convenience of use, durability, clarity of instructions and device preferences of
patients. This study compares the satisfaction and preference, as well as error
occurrence, with the use of Genuair(r), ElliptaTM and BreezhalerTM by healthy
subjects in Hong Kong. Subjects and methods: One hundred and thirty healthy Hong
Kong Chinese subjects aged >=40 years without a previous diagnosis of COPD and
asthma and with no experience of using dry powder inhalers (DPIs) were recruited.
Subjects learned to use the three DPIs by initially reading the instructions and
then observing a demonstration with verbal explanation. The number of errors
committed was evaluated. Subjects also completed a questionnaire to indicate
their satisfaction and preference. Results: The satisfaction score of comfort for
Breezhaler was significantly higher than that for Ellipta (p<=0.05), while the
satisfaction score on confidence to have inhaled the entire dose was highest for
Genuair compared with Ellipta (p<=0.0001) or Breezhaler (p<=0.05). The overall
satisfaction score was significantly higher for Genuair than Ellipta (p<=0.05) or
Breezhaler (p<=0.01). After reading the instructions, the highest number of
subjects committing one or more critical errors was with Breezhaler (97) followed
by Genuair (70) and then Ellipta (33). Demonstration reduced the number of
critical errors made by subjects for each DPI to one third or lower. Conclusion:
Breezhaler seemed to be more comfortable and easy to carry, but users made less
critical errors when using Ellipta after reading the instructions only. Genuair
provided the clearest indication of correct dose preparation and inhalation.
PMID- 29942128
TI - Enhancement of surface bioactivity on carbon fiber-reinforced polyether ether
ketone via graphene modification.
AB - Background and objective: The modulus of carbon fiber-reinforced polyether ether
ketone (CFR-PEEK), a composite containing layers of carbon fiber sheets, can be
precisely controlled to match bone. However, CFR-PEEK is biologically inert and
cannot promote bone apposition. The objective of this study was to investigate
whether graphene modification could enhance the bioactivity of CFR-PEEK. Methods
and results: In vitro, the proliferation and differentiation of rat bone marrow
stromal cells on scaffolds were quantified via cell-counting kit-8 assay and
Western blotting analysis of osteoblast-specific proteins. Graphene modification
significantly promoted bone marrow stromal cell proliferation and accelerated
induced differentiation into osteogenic lineages compared to cells seeded onto
nongraphene-coated CFR-PEEK. An in vivo rabbit extraarticular graft-to-bone
healing model was established. At 4, 8, and 12 weeks after surgery, microcomputed
tomography analyses and histological observations revealed significantly better
microstructural parameters and higher average mineral apposition rates for
graphene-modified CFR-PEEK implants than CFR-PEEK implants (P<0.05). van Gieson
staining indicated more new bone was formed around graphene-modified CFR-PEEK
implants than CFR-PEEK implants. Conclusion: Graphene may have considerable
potential to enhance the bioactivity and osseointegration of CFR-PEEK implants
for clinical applications.
PMID- 29942129
TI - Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective
glioma treatment.
AB - Background: The treatment of glioma remains a challenge because conventional
chemotherapy is often ineffective by drug resistance. Combinative therapy using
chemotherapeutic agents and siRNA has demonstrated potential to improve
anticancer outcome through a synergistic effect in various cancers. The current
study aims to achieve better glioma treatment through a combinative therapy based
on a folate-targeted nanocarrier carrying both temozolomide (TMZ) and anti-BCL-2
siRNA. Methods: A polymeric micelle (TMZ-FaPEC@siRNA) incorporating TMZ and anti
BCL-2 siRNA was prepared based on folate-conjugated triblock copolymer (Fa-PEG
PEI-PCL, Fa-PEC) of poly(epsilon-caprolactone) (PCL), poly(ethylenimine) (PEI)
and poly(ethylene glycol) (PEG). The physicochemical properties and drug release
profile of TMZ-FaPEC@siRNA were tested. The Fa-targeted drug delivery and joint
effect of siRNA and TMZ to induce glioma apoptosis and tumor growth inhibition
were evaluated both in vitro and in vivo. Results: In vitro cell study
demonstrated that the nanocarrier effectively facilitates codelivery of siRNA and
TMZ into C6 cells, resulting in a strong apoptotic response of cancer cells by
silencing the antiapoptosis BCL-2 gene and activating the proapoptotic Bax gene
simultaneously. In vivo study in rat bearing orthotropic glioma showed that tumor
growth was inhibited and meanwhile animal survival was prolonged remarkably
through intracranial injection of TMZ-FaPEC@siRNA. Conclusion: Our results
evidence the strong efficacy of the folate-targeted nanomedicine carrying TMZ and
BCL-2 siRNA in treating glioma.
PMID- 29942130
TI - Risk assessment of night-eating syndrome occurrence in women in Poland,
considering the obesity factor in particular.
AB - Introduction: Night-eating syndrome (NES) involves uncontrolled and most often
repeated binge eating during the night. It is related with mood disorders as well
as sleep disorders and it may cause obesity. Risks related to NES are obesity,
binge eating disorder, bulimia nervosa, affective disorders, and sleep disorders.
The objective of this study is to analyze eating habits in terms of the risk
assessment of NES occurrence in the population of women in the Masovian
Voivodeship (in Poland). Patients and methods: Six hundred and eleven women
living in the Masovian Voivodeship participated in the study. The average age of
the respondents was 22.7 years (median = 23.0; interquartile range = 3.0). The
Night Eating Questionnaire (NEQ) was used to assess the risk of NES. Results: In
the studied group of women, 1.3% of cases (N = 12) reached a NEQ total score of
>=25, which indicates a probability of 40.7% for NES, while 0.7% (N = 4) reached
a score of >=30, which indicates a probability of 72.2% for occurrence of this
syndrome. The highest average total score was observed in the group of obese
people. The level of education of the participants did not significantly affect
the NEQ score. A weak correlation was observed between the place of residence
variable and the mood/sleep subscale (r = 0.11, P < 0.01). Conclusion: NES may be
one of the causes of overweight and obesity; therefore, the need for further
studies on this health issue is justified. It is worth pointing out that knowing
the conditions responsible for the occurrence of NES, it is possible to suggest a
prevention procedure for this condition.
PMID- 29942131
TI - Agomelatine versus fluoxetine in glycemic control and treating depressive and
anxiety symptoms in type 2 diabetes mellitus subjects: a single-blind randomized
controlled trial.
AB - Background: Depressive and anxiety symptoms could seriously affect the quality of
life of type 2 diabetes mellitus (T2DM) subjects. Currently, little is known
about the efficacy and acceptability of agomelatine versus fluoxetine in treating
these symptoms in T2DM subjects. Therefore, this study was performed to find out
which one was better in treating these symptoms in T2DM subjects. Materials and
methods: T2DM subjects with depressive and anxiety symptoms were randomly
assigned to receive either fluoxetine (30-40 mg/day) or agomelatine (25-50
mg/day). The treatment was continued for 12 weeks. The data of the Hamilton
Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were
collected (at baseline and also at weeks 4, 8 and 12) to assess the depressive
and anxiety symptoms, respectively. The metabolic parameters, including body mass
index (BMI), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c), were
assessed at baseline and after 12 weeks of treatment. The treatment-related
adverse events during the scheduled treatment period were recorded to compare the
acceptability of these two drugs. Results: After 12 weeks of treatment, the
average HDRS and HARS scores were significantly decreased in both groups. The
average HDRS scores were not significantly different between the two groups,
although the agomelatine group had a lower average HDRS score. The response and
remission rates were similar between the two groups, and these two drugs had no
significant effects on BMI and FPG. However, compared with the fluoxetine group,
the agomelatine group had the significantly lower average HARS score (p=0.0017)
and lower average HbA1c level (p<0.00001). Moreover, the incidence of adverse
events was significantly lower in the agomelatine group than in the fluoxetine
group (p=0.032). Conclusion: Both fluoxetine and agomelatine could effectively
reduce depressive and anxiety symptoms in T2DM subjects, but agomelatine might be
more effective and acceptable. Future studies with more subjects are needed to
support and validate our conclusion.
PMID- 29942133
TI - Preoperative practice of surgical position reduces postoperative pain and
discomfort in patients receiving kidney surgeries: a nonrandomized pilot study.
AB - Objective: Prolonged maintenance of surgical position often results in
postoperative pain and discomfort in patients. The present study aimed to
investigate the effect of preoperative practice of surgical position on
postoperative pain and general comfort in patients receiving kidney surgeries.
Methods: For this nonrandomized pilot study, 74 patients receiving kidney
surgeries were selected using the probability sampling method. Patients from ward
1 were assigned to the practice group (n=35), and those from ward 2 were assigned
to the control group (n=39). The practice group were instructed to practice the
surgical position for 3 days prior to the surgery. Postoperative pain and comfort
were surveyed using two questionnaires for 3 days, respectively. The
postoperative pain scores were compared using the Student's t-test. Results: The
two groups did not differ significantly in wound pain on postoperative days 1-3
(P > 0.05). However, the practice group showed significantly reduced low back
pain and contralateral shoulder pain than the control group for 3 postoperative
days (P < 0.05). The physical domain score was significantly higher in the
practice group than in the control group (P < 0.01). Conclusion: Preoperative
practice of surgical position can effectively reduce postoperative low back pain
and contralateral shoulder pain in patients receiving kidney surgeries and
improve the physical comfort.
PMID- 29942132
TI - Structural equation modeling approach between salience network dysfunction,
depressed mood, and subjective quality of life in schizophrenia: an ICA resting
state fMRI study.
AB - Purpose: Quality of life (QOL) is an important clinical outcome for patients with
schizophrenia, and recent studies have focused on subjective QOL. We evaluated
the causal relationship between psychosocial aspect of subjective QOL, symptoms,
cognitive functions, and salience network (SN) dysfunction in schizophrenia using
structural equation modeling (SEM). Patients and methods: We performed a cross
sectional study of 21 patients with symptomatically stabilized schizophrenia and
21 age-, sex-, and education level-matched healthy controls who underwent resting
state functional magnetic resonance imaging. We evaluated SN dysfunction in
schizophrenia using independent component analysis (ICA). We rated participant
psychopathology using the Positive and Negative Syndrome Scale (PANSS), the Brief
Assessment of Cognition in Schizophrenia (BACS), and the Calgary Depression Scale
for Schizophrenia (CDSS). We rated psychosocial aspect of subjective QOL using
the Schizophrenia Quality of Life Scale (SQLS) psychosocial subscale. We applied
SEM to examine the relationships between SN dysfunction, PANSS positive and
negative scores, CDSS total scores, BACS composite scores, and SQLS psychosocial
subscale scores. Results: In second-level analysis after group ICA, patient group
had significant lower right pallidum functional connectivity (FC) within the SN
than the controls did (Montreal Neurological Institute [MNI] [x y z] = [22 -2
6]) (p = 0.027, family-wise error [FWE] corrected). In SEM, we obtained a good
fit for an SEM model in which SN dysfunction causes depressed mood, which in turn
determines psychosocial aspect of subjective QOL (chi-squared p = 0.9, root mean
square error of approximation (RMSEA) < 0.001, comparative fit index [CFI] =
1.00, and standardized root mean square residual [SRMR]= 0.020). Conclusion: We
found a continuous process by which SN dysfunction causes depressed moods that
determine psychosocial aspect of subjective QOL in schizophrenia. This is the
first report that offers a unified explanation of functional neuroimaging,
symptoms, and outcomes. Future studies combining neuroimaging techniques and
clinical assessments would elucidate schizophrenia's pathogenesis.
PMID- 29942134
TI - Collaborative intervention between pharmacists and physicians on elderly
patients: a randomized controlled trial.
AB - Background: The elderly population is the largest consumer of medications as this
age group is at high risk for developing chronic diseases. However, medication
use among elderly people is complicated by an increased risk of drug-related
problems. Therefore, the present study was conducted to investigate the effects
of collaborative interventions between pharmacists and physicians on health
related outcomes of elderly patients. Patients and methods: This was a randomized
controlled trial (RCT) conducted on elderly outpatients who sought treatment in
the Medical Outpatient Department of a public tertiary hospital in Malaysia and
who were taking at least five medications. The participants were randomly
allocated to the intervention and control groups. The intervention group received
pharmaceutical care from a pharmacist in collaboration with physicians and was
followed-up for 6 months, while the control group received usual care in the
outpatient pharmacy. Results: A total of 73 participants in the intervention
group and 79 participants in the control group completed the study. Participants
in the intervention group had significantly better medication adherence (median
=7.0 vs 5.0, U=1224.5, p<0.001, r=0.503) and better Medication Appropriateness
Index (MAI) score (median =8.0 vs 20.0, U=749.5, p<0.001, r=0.639). Conclusion:
Collaborative interventions between pharmacists and physicians improved
medication adherence and MAI scores of the elderly patients. Therefore, such
services should be implemented in all hospitals, especially in countries where
pharmacists are still not playing a substantial role in patient care. Trial
registration: NMRR-12-958-13020.
PMID- 29942135
TI - Effectiveness of lomustine and bevacizumab in progressive glioblastoma: a meta
analysis.
AB - Background: Glioblastomas (GBMs) are the most aggressive type of glial brain
tumors. Despite aggressive treatment with surgery and chemoradiation, GBMs
invariably relapse and tumors are progressive. Controversy remains on optimal
treatment of patients with recurrent GBMs. Data from previous trials have
suggested that the addition of bevacizumab (BEV) to lomustine (CCNU) might
improve overall survival (OS) as compared with that with monotherapies. The aim
of this study was to compare the efficacy of BEV in addition to CCNU versus
single-agent therapy in patients with recurrent GBM. Methods: Electronic
databases were searched for eligible literature updated in December 2017. Trials
assessing the effectiveness of CCNU and BEV in progressive GBM were included, of
which the main outcomes were progression-free survival (PFS) and OS. All the data
were pooled with the corresponding 95% confidence intervals (CIs) using RevMan
software. Sensitivity and heterogeneity were quantitatively evaluated. Results:
Three randomized clinical trials were identified, including 574 patients
(combination group: 358, monotherapies group: 216). The combination group treated
with BEV and CCNU showed improvement in PFS (OR = 0.49; 95% CI, 0.41-0.59; p <
0.00001). No significant differences were, however, found in patients in terms of
the OS (OR = 0.84; 95% CI, 0.68-1.03; p = 0.09). Conclusion: Although treatment
with CCNU plus BEV prolonged PFS, it did not confer OS advantage over
monotherapies in patients with progressive GBM. The encouraging results of the
addition of CCNU to BEV warrant investigation in further randomized trials.
PMID- 29942136
TI - Comparison of the prognosis of neoadjuvant chemoradiotherapy treatment with
surgery alone in esophageal carcinoma: a meta-analysis.
AB - Background: Resection remains the best treatment for carcinoma of the esophagus
in terms of local control, but local recurrence and distant metastasis remain an
issue after surgery. Chemo-radiotherapy (CRT) followed by surgery was associated
with significantly improved survival benefit, but the effectiveness of
neoadjuvant therapy in patients with resectable esophageal carcinoma remains
controversial. The aim of this study was to evaluate the effects of neoadjuvant
chemoradiotherapy in resectable esophageal carcinoma compared to surgery alone
(SA). Methods: A search for publications that compared the efficacy of CRT with
SA in resectable esophageal carcinoma was conducted. After a rigorous review of
the quality, the data were extracted from eligible trials. The major outcomes
measures were odds ratios (ORs). The ORs with their corresponding 95% confidence
intervals were the principal measure of effects. For the meta-analysis, Revman
5.3 software was used to analyze the combined pooled ORs using fixed- or random
effects models according to the heterogeneity. Results: Our findings revealed
that, compared with SA, neoadjuvant CRT was associated with improved overall
survival (OS) and progression-free survival times, but the 3- and 5-year OS did
not show a statistical difference (P>=0.05). The adjuvant chemotherapy group did
not show significant improvement on reference rate and metastasis rate compared
with the control group. Conclusion: CRT does significantly improve progression
free survival and OS in patients with esophageal cancer compared with SA.
However, further assessment is still warranted on the role of CRT in future
trials with well-selected patients.
PMID- 29942137
TI - The association of pretreatment serum albumin with outcomes in bladder cancer: a
meta-analysis.
AB - Background: Recently, numerous studies have shown that pretreatment serum albumin
can be closely associated with the prognosis of patients with bladder cancer
(BC). However, the conclusions regarding this issue are still conflicting. Hence,
in this study, we performed a systematic review and meta-analysis to determine
the prognostic significance of pretreatment serum albumin in BC patients.
Materials and methods: A systematic search was carried out in PubMed, Embase, and
Web of Science. A total of 16 studies involving 13,917 patients were included in
the current meta-analysis. hazard ratios (HRs) and 95% CIs were pooled to assess
the intensity of association. Moreover, heterogeneity, sensitivity analysis and
publication bias were explored. All statistical analyses were conducted by STATA
12.0. Results: Our results suggested that a decreased pretreatment serum albumin
level was closely related to a worse overall survival (HR 1.88, 95% CI 1.43,
2.48; P<0.01) and cancer-specific survival (HR 1.65, 95% CI 1.08, 2.52; P=0.02).
In addition, from the results of this meta-analysis, it was also observed that a
lower pretreatment serum albumin level was linked to higher incidence of
postoperative 30-day complication (odds ratio [OR] 1.41, 95% CI 1.03, 1.91;
P=0.03) and 90-day mortality (OR 2.51, 95% CI 1.82, 3.48; P<0.01). Furthermore,
these findings were demonstrated to be reliable by our sensitivity and subgroup
analysis stratified by ethnicity, analysis type, and cutoff value. Conclusion:
Our results revealed that a lower pretreatment serum albumin level yields a poor
long-term prognosis and increases the risks of postoperative complication and
mortality in BC patients and can be applied to risk stratification and
individualized therapy in BC patients.
PMID- 29942138
TI - MALAT1 silencing suppresses prostate cancer progression by upregulating miR-1 and
downregulating KRAS.
AB - Background: Prostate cancer (PC) is the second leading cause of cancer-related
deaths among men. Long noncoding RNA metastasis-associated lung adenocarcinoma
transcript 1 (MALAT1) performed as an oncogene in multiple cancers including PC.
However, the molecular mechanisms of MALAT1 implicated in PC progression have not
been thoroughly elaborated. Materials and methods: Reverse transcription
quantitative polymerase chain reaction assay was used to detect the expressions
of MALAT1 and microRNA-1 (miR-1). Protein levels of cleaved poly (ADP-ribose)
polymerase, cleaved caspase-3, BAX, bcl-2, and KRAS were determined using a
western blot assay. Cell proliferation was assessed by colony formation and MTS
assays. Cell migration capacity was examined by transwell migration assay
(Corning Incorporated, Corning, NY, USA). Apoptosis rate was measured by flow
cytometry via double staining of annexin V-FITC and propidium iodide. Luciferase
and RNA immunoprecipitation assays were employed to explore the relationship
among miR-1, MALAT1, and KRAS. Results: MALAT1 expression was upregulated and miR
1 expression was downregulated in PC tissues and cell lines. MALAT1 knockdown
inhibited cell proliferation and migration, and promoted cell apoptosis in
androgen receptor-negative DU145 and PC3 cells. Molecular mechanism explorations
disclosed that MALAT1 acted as a molecular sponge of miR-1 in DU145 cells.
Moreover, miR-1 downregulation partly abrogated MALAT1 silencing-mediated anti
proliferative, antimigratory, and proapoptotic effects in DU145 and PC3 cells.
Further investigation revealed that KRAS was a target of miR-1 in DU145 cells.
MALAT1 acted as a competing endogenous RNA of miR-1, resulting in the increase of
KRAS expression in DU145 and PC3 cells. Furthermore, miR-1 overexpression
hampered proliferation and migration and promoted apoptosis in DU145 and PC3
cells, while these effects were markedly weakened following KRAS upregulation.
Conclusion: MALAT1 knockdown inhibited proliferation and migration and
facilitated apoptosis by upregulating miR-1 and downregulating KRAS in androgen
receptor-negative PCa cells, providing a new insight into the molecular basis of
MALAT1 and a potential biomarker or therapeutic target for suppressing castration
resistant PC.
PMID- 29942139
TI - STAT3 induces colorectal carcinoma progression through a novel miR-572-MOAP-1
pathway.
AB - Purpose: Colorectal carcinoma (CRC) is among the most common causes of death.
Recent studies have shown that both STAT3 and miR-572 contribute to CRC
progression. STAT3 plays an important role in miRNA expression. Moreover, MOAP-1,
which is a pro-apoptotic protein that induces cell death or apoptosis, has a
direct correlation with miRNA. Therefore, the current study is designed to
explore whether miR-572 and STAT3 are involved in a common pathway and the role
of MOAP-1 in this process. Patients and methods: The expressions of STAT3, miR
572, and MOAP-1 in human CRC tissues and multiple cell lines were estimated by
qRT-PCR or Western blot. MTT, transwell migration, and invasion assays were used
to assess cell growth, migration, and invasion, respectively. Dual-luciferase
reporter assay was applied to examine the association between miR-572 and MOAP-1.
Results: Elevated STAT3 levels were accompanied by increased miR-572 and
decreased MOAP-1 levels in primary CRC specimens and cell lines. STAT3 promoted
CRC cell growth, migration, and invasion via the upregulated expression of miR
572. Subsequently, miR-572 inhibited MOAP-1 protein expression through an
interaction with its 3'UTR. Conclusion: Our study proposes a novel STAT3-miR-572
MOAP-1 pathway involved in the process of CRC progression, which might be a
potential target for the development of new preventive and therapeutic approaches
against human colorectal cancer.
PMID- 29942140
TI - Downregulation of ribophorin II suppresses tumor growth, migration, and invasion
of nasopharyngeal carcinoma.
AB - Background: It has been reported that ribophorin II (RPN2) expression is
increased in many cancers, but the role of RPN2 in nasopharyngeal carcinoma (NPC)
remains unclear. Patients and methods: This study found that the expression of
RPN2 is increased dramatically in NPC tissues of patients compared with that in
the adjacent normal tissues. This study attempted at understanding the effect of
siRNA-RPN2 treatment on the migration and invasion of NPC cell lines CNE2 and
HNE1. Results: RT-PCR and Western blotting showed that RPN2 was highly expressed
in CNE2 and HNE1 cells. siRNA-RPN2 treatment significantly inhibited cell
viability at 24 and 48 h compared with the control group. Results of the
transwell assay showed that, compared to the control groups, migration and
invasion of the cells treated with siRNA-RPN2 decreased markedly. In addition,
compared to the control groups, caspase-3, caspase-9, and E-cadherin expression
levels increased and MMP 2 expression decreased significantly in the siRNA-RPN2
treated group. Phosphorylation of AKT and PI3K was also inhibited after siRNA
RPN2 treatment. Conclusion: siRNA-RPN2 can effectively inhibit the invasion and
migration of human NPC cells via AKT/PI3K signaling. This can serve as a novel
strategy for NPC treatment.
PMID- 29942141
TI - Mutation EthAW21R confers co-resistance to prothionamide and ethionamide in both
Mycobacterium bovis BCG and Mycobacterium tuberculosis H37Rv.
AB - Ethionamide (ETA) and prothionamide (PRO) are interchangeably used in
tuberculosis (TB) chemotherapy regimens. Subtle discrepancies between biochemical
and genetic information on the modes of sensitivity and resistance of isoniazid
(INH) and ETA warrants further studies. We report a new mutation - EthAW21R - in
Mycobacterium bovis Bacillus Calmette-Guerin that corresponds with co-resistance
to both PRO and ETA, which to the best of our knowledge has not been reported
before. Our findings suggest that mutation EthAW21R could be used as a marker
site for testing PRO and ETA cross-resistance.
PMID- 29942142
TI - Chronic oscillating glucose challenges disarrange innate immune homeostasis to
potentiate the variation of neutrophil-lymphocyte ratio in rats with or without
hidden diabetes mellitus.
AB - Background: The neutrophil-lymphocyte ratio (NLR) has been considered as an
inflammatory marker in various disorders, but it is not clear whether the NLR is
also elevated with hidden diabetes (HD), which is normal in fasting blood glucose
(FBG) but abnormal in the oral glucose tolerance test (OGTT). Materials and
methods: An HD animal model for 27 days and an animal model with oscillating
glucose (OG) for 7 days were applied on adult female Sprague-Dawley rats. OGTT,
leukogram analysis, histology, and immunohistochemistry were carried out.
Results: In HD rats, the percentage of neutrophils increased but the percentage
of lymphocytes decreased; hence, the NLR rose relative to sham. This may be a
result of the OG levels often experienced by diabetic subjects, as normal rats
given OG (6 g/kg/6 h) for 7 days had significantly reduced lymphocyte numbers and
increased NLR compared with the values before and 1 h after oral glucose
administration during OGTT. Glucose-induced disarrangement of partitions of
circulating immune cells and NLR was involved in the increase in oxidative
stress, as these changes were totally blocked by the antioxidant glutathione
(GSH). GSH (50 mg/kg/6 h) totally blocked the glucose-induced alterations in
lymphocyte and NLR values. Conclusion: HD associated with elevation of NLR values
may be partly attributed to a homeostasis disorder of the innate inflammatory
state, caused by oscillating hyperglycemia. Acute high glucose administration
produced a significant decrease in lymphocyte number. OG administration
potentiated this effect and increased the NLR value, which was blocked by GSH,
suggesting that reactive oxygen species play a critical role in maintaining
lymphocyte numbers.
PMID- 29942144
TI - Association of serum procalcitonin and C-reactive protein levels with CURB-65
criteria among patients with community-acquired pneumonia.
AB - Background: The concentration of diagnostic markers such as inflammatory
biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) increases
in bacterial infections. The aim of this study was to compare serum PCT and CRP
levels with CURB-65 ranking, in the patients with community-acquired pneumonia
(CAP). Patients and methods: In a cross-sectional study, 93 hospitalized patients
with a definite diagnosis of CAP, considering inclusion and exclusion criteria,
were enrolled. Serum PCT and CRP levels and their relations with CURB-65 criteria
were assessed. Results: The mean serum levels of PCT and CRP were 3.64+/-12.32
ng/mL and 75.01+/-51.93 mg/L, respectively. There was a statistically significant
association between CURB-65 criteria and serum levels of PCT (P=0.0001) and CRP
(P=0.007), which means that the concentration of these two inflammatory
biomarkers increased with an increase in the score of CURB-65 criteria. Moreover,
there was a statistically significant association between the serum level of PCT
and the outcomes of the disease (P<0.001). Conclusion: According to the results,
the serum level of PCT or CRP is a strong prognostic factor for evaluating
severity of CAP and is a suitable factor for the CURB-65 criteria in the decision
making of whether a patient with CAP in the ICU should be admitted.
PMID- 29942143
TI - Proteomic analysis to identify candidate biomarkers associated with type 1
diabetes.
AB - Purpose: Type 1 diabetes mellitus (DM1) is one of the most common chronic
diseases observed during childhood. The incidence of DM1 is increasing worldwide,
and there is currently no way to prevent or delay the onset or to cure the
disease. Most diseases, including diabetes, stem from abnormalities in the
functioning of proteins, and some studies have reported the expression of protein
variation to be involved in the development of DM1. Thus, the aim of this study
was to investigate the differential expression of serum proteins in patients with
DM1. Materials and methods: Serum of patients with DM1 (n=30) and healthy
controls (n=30) was collected. A proteomic approach was used with depletion of
albumin and immunoglobulin G chromatography on serum samples followed by data
independent, label-free mass spectrometric analysis. Results: A total of eight
serum proteins were identified as being differentially expressed and involved in
the immune system, lipid metabolism, and pathways of coagulation. DM1 was
associated with the upregulation of six proteins: alpha-2-macroglobulin,
apolipoprotein A-II, beta2 glycoprotein I, Ig alpha-2 chain C region, alpha-1
microglobulin, and prothrombin. A total of two proteins were downregulated,
including pregnancy zone protein and complement C4. Conclusion: To the best of
our knowledge, these findings show differential expression of proteins revealing
new proteins that may be involved in the development and progression of diabetes.
PMID- 29942145
TI - Clinical pain, abstraction, and self-control: being in pain makes it harder to
see the forest for the trees and is associated with lower self-control.
AB - Objectives: Although abstract thinking is a fundamental dimension of human
cognition, it has received scant attention in research on pain and cognition. We
hypothesized that physical pain impairs abstraction, because when people
experience pain at high intensity levels, attention becomes concretely focused on
the self in the here and now, where little else matters than finding relief for
the pain they are currently experiencing. We also examined the relationship
between pain and self-control, predicting that pain would debilitate self
control. Patients and methods: Abstraction and self-reported self-control were
assessed in 109 patients with musculoskeletal pain. The influence of specific
pain qualities, such as pain intensity, pain interference with daily activities,
pain duration, and pain persistence, was examined. Furthermore, we assessed other
factors (e.g., anxiety, depression, and fatigue) that could be assumed to play a
role in the pain experience and in cognitive performance. Results: Higher pain
intensity and persistence were associated with less abstract thinking.
Furthermore, self-control decreased with greater pain intensity, persistence, and
self-reported pain interference with daily activities. Self-reported depressive
symptoms mediated the overall relationship between pain and self-control.
Conclusion: Abstraction is compromised in patients reporting higher pain
intensity and persistence. Different dimensions of pain also predict lower self
control although depression seems to account for the relationship between overall
pain and self-control. The current study is the first to report an association
between clinical musculoskeletal pain and abstraction. The results suggest that
pain patients may suffer from a broader range of cognitive disadvantages than
previously believed.
PMID- 29942146
TI - A retrospective case series of ultrasound-guided suprascapular nerve pulsed
radiofrequency treatment for hemiplegic shoulder pain in patients with chronic
stroke.
AB - Purpose: Hemiplegic shoulder pain (HSP) is the most common pain condition after
stroke. Pulsed radiofrequency (PRF) treatment of the suprascapular nerve (SSN)
effectively relieves shoulder pain conditions. To date, there is no study about
the effects of PRF treatment for HSP. Thus, our aim was to report on a case
series about its use in chronic stroke. Patients and methods: Six chronic stroke
patients with HSP (visual analog scale [VAS] score for pain >=30 mm) underwent
ultrasound-guided SSN PRF treatment. All were evaluated before treatment and at 4
and 16 weeks of follow-up. The main outcome was VAS score. Secondary outcomes
were Modified Ashworth Scale, shoulder passive range of motion (PROM), Disability
Assessment Scale (DAS), Fugl-Meyer Assessment, and EuroQol-5 dimension
questionnaire (EuroQol-5D) scores. Results: As compared with baseline,
improvement was observed in the following parameters: VAS for pain (at 4 weeks,
P=0.023; at 16 weeks, P=0.023); shoulder PROM for abduction (at 4 weeks, P=0.023;
at 16 weeks, P=0.024), flexion (at 4 and 16 weeks, P=0.024), extension (at 4 and
16 weeks, P=0.02), and external rotation (4 and 16 weeks, P=0.02); DAS for
hygiene (at 4 and 16 weeks, P=0.024), dressing (at 4 weeks, P=0.02; at 16 weeks,
P=0.024), and pain (at 4 weeks, P=0.024; at 16 weeks, P=0.023); and EuroQol-5D
(at 4 and 16 weeks, P=0.024). Conclusion: Our observations support the use of
ultrasound-guided SSN PRF treatment for HSP in chronic stroke patients.
PMID- 29942147
TI - The roles of gender and profession on gender role expectations of pain in health
care professionals.
AB - Introduction: Gender-related stereotypes of pain may account for some assessment
and treatment disparities among patients. Among health care providers,
demographic factors including gender and profession may influence the use of
gender cues in pain management decision-making. The Gender Role Expectations of
Pain Questionnaire was developed to assess gender-related stereotypic
attributions of pain regarding sensitivity, endurance, and willingness to report
pain, and has not yet been used in a sample of health care providers. The purpose
of this study was to examine the presence of gender role expectation of pain
among health care providers. It was hypothesized that health care providers of
both genders would endorse gender stereotypic views of pain and physicians would
be more likely than dentists to endorse these views. Methods: One-hundred and
sixty-nine providers (89 dentists, 80 physicians; 40% women) were recruited as
part of a larger study examining providers' use of demographic cues in making
pain management decisions. Participants completed the Gender Role Expectations of
Pain Questionnaire to assess the participant's views of gender differences in
pain sensitivity, pain endurance, and willingness to report pain. Results:
Results of repeated measures analysis of variance revealed that health care
providers of both genders endorsed stereotypic views of pain regarding
willingness to report pain (F(1,165)=34.241, P<0.001; d=0.479). Furthermore,
female dentists rated men as having less endurance than women (F(1,165)=4.654,
P=0.032; d=0.333). Conclusion: These findings affirm the presence of some gender
related stereotypic views among health care providers and suggest the presence of
a view among health care providers that men are underreporting their pain in
comparison to women. Future work can refine the effects of social learning
history and other psychosocial factors that contribute to gender and provider
differences in pain management decisions.
PMID- 29942148
TI - alpha7 Nicotinic acetylcholine receptor-mediated anti-inflammatory effect in a
chronic migraine rat model via the attenuation of glial cell activation.
AB - Background: Evidence suggests that the activation of alpha7 nicotinic
acetylcholine receptor (alpha7nAChR) can greatly decrease the neuroinflammation
response. Neuroinflammation plays a pivotal role in the pathogenesis of chronic
migraine (CM). Clinical observations also show that nicotine gum induces
analgesic effects in migraine patients. However, whether alpha7nAChR is involved
in CM is unclear. Objective: To investigate the role of alpha7nAChR in CM and
provide a new therapeutic target for CM. Materials and methods: Thirty-six male
Sprague-Dawley rats were distributed randomly into control, CM, PNU-282987, and
alpha-bungarotoxin groups (n=9 rats in each group). The CM model was established
by the recurrent daily administration of inflammatory soup on the dura over the
course of 1 week. The hind paw threshold and facial allodynia were assessed by
the von Frey test. The expression levels of alpha7nAChR, tumor necrosis factor
alpha, and interleukin-1 beta were analyzed by Western blot and real-time
fluorescence quantitative polymerase chain reaction. The location of alpha7nAChR
in the hippocampus was quantified by immunofluorescence, as well as the
microglial and astrocyte alterations. Changes in the calcitonin gene-related
peptide and the phosphorylated JNK protein among different groups were measured
by Western blot. Results: We found that the expression of alpha7nAChR was reduced
after repeated inflammatory soup administration. The increased expression of
tumor necrosis factor-alpha, interleukin-1 beta, and calcitonin gene-related
peptide in CM group were significantly decreased by PNU-282987 and aggravated by
alpha-bungarotoxin. Moreover, PNU-282987 decreased the numbers of astrocytes and
microglia compared with the numbers in the CM group in both hippocampal CA1 and
CA3 regions. In contrast, alpha-bungarotoxin activated the astrocytes and
microglia, but the differences with respect to the CM group were not significant.
Activated c-Jun N-terminal kinase signaling was observed in CM rats and was also
blocked by PNU-282987. Conclusion: The activation of alpha7nAChR increased the
mechanical threshold and alleviated pain in the CM rat model. alpha7nAChR
activation also decreased the upregulation of astrocytes and microglia through
the p-c-Jun N-terminal kinase-mitogen-activated protein kinase signaling pathway.
PMID- 29942149
TI - Real-world insights on the use of transversus abdominis plane block with
liposomal bupivacaine in the multimodal management of somatic versus visceral
pain in the colorectal surgery setting.
PMID- 29942150
TI - Ovine model of neuropathic pain for assessing mechanisms of spinal cord
stimulation therapy via dorsal horn recordings, von Frey filaments, and gait
analysis.
AB - Background: It is becoming increasingly important to understand the mechanisms of
spinal cord stimulation (SCS) in alleviating neuropathic pain as novel
stimulation paradigms arise. Purpose: Additionally, the small anatomic scale of
current SCS animal models is a barrier to more translational research. Methods:
Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in
sheep (ovine), we have created a chronic model of neuropathic pain that avoids
motor deficits present in prior large animal models. This large animal model has
allowed us to implant clinical grade SCS hardware, which enables both acute and
chronic testing using von Frey filament thresholds and gait analysis.
Furthermore, the larger anatomic scale of the sheep allows for simultaneous
single-unit recordings from the dorsal horn and SCS with minimal electrical
artifact. Results: Detectable tactile hypersensitivity occurred 21 days after
nerve injury, with preliminary indications that chronic SCS may reverse it in the
painful limb. Gait analysis revealed no hoof drop in the CCI model. Single
neurons were identified and discriminated in the dorsal horn, and their activity
was modulated via SCS. Unlike previous large animal models that employed a
complete transection of the nerve, no motor deficit was observed in the sheep
with CCI. Conclusion: To our knowledge, this is the first reported large animal
model of chronic neuropathic pain which facilitates the study of both acute and
chronic SCS using complementary behavioral and electrophysiologic measures. As
demonstrated by our successful establishment of these techniques, an ovine model
of neuropathic pain is suitable for testing the mechanisms of SCS.
PMID- 29942151
TI - Role of palliative radiotherapy in unresectable intrahepatic cholangiocarcinoma:
population-based analysis with propensity score matching.
AB - Background: This population-based study evaluated the overall (OS) and cancer
specific survival (CSS) benefit from palliative radiotherapy (RT) in patients
with unresectable intrahepatic cholangiocarcinoma (ICC). Methods: We queried The
Surveillance, Epidemiology, and End Results (SEER) database for the patients with
unresectable ICC diagnosed from 1973 to 2013. Propensity score-matched analysis
was performed to reduce the impact of the selection bias between the palliative
RT group and the nonpalliative RT group. Kaplan-Meier survival curves were used
to estimate the survival outcome before and after propensity score matching. OS
and CSS were compared between patients with and without palliative RT using
univariate and multivariate Cox proportional hazards regression analyses.
Results: A total of 4,027 of 15,803 patients diagnosed with ICC were included in
this study. Of those, 847 (21%) patients underwent palliative RT, whereas 3,180
(79%) did not. In the unmatched population, patients treated with palliative RT
had improved OS and CSS relative to those treated without palliative RT (adjusted
HR =0.9065, 95% CI =0.8360-0.982, P=0.01735) and CSS (adjusted HR =0.8874, 95% CI
=0.8160-0.9652, P=0.00532). After propensity score matching, palliative RT was
associated with a significantly improved OS (adjusted HR =0.8544, 95% CI =0.7722
0.9453, P=0.00228) and CSS (adjusted HR =0.8563, 95% CI =0.7711-0.9509,
P=0.0037). Conclusion: Palliative RT seems to improve the prognosis of patients
with unresectable ICC.
PMID- 29942152
TI - A two-microRNA signature as a diagnostic and prognostic marker of pancreatic
adenocarcinoma.
AB - Background and aim: Some cancer-specific miRNAs are dysregulated in pancreatic
adenocarcinoma (PAAD) and involved in cell autophagy, differentiation,
proliferation, migration, invasion, and malignant transformation. The aim of our
study was to determine a panel of new diagnostic and prognostic biomarkers for
PAAD. Methods: We conducted a comprehensive analysis of global miRNA-expression
profiles and corresponding prognosis information of 168 PAAD patients from the
Cancer Genome Atlas data set. A total of 16 differentially expressed miRNAs were
identified as aberrantly expressed in PAAD, and six of these were evaluated for
use as diagnostic markers for PAAD. Next, we confirmed a two-miRNA signature
significantly associated with PAAD patient diagnosis and outcome prediction.
Results: The panel of two miRNAs showed outstanding diagnostic performance, with
sensitivity of 100% and specificity of 87.5%. Finally, we divided the PAAD
patients into high-risk and low-risk groups based on the expression profile of
the two miRNAs. Kaplan-Meier analysis demonstrated that patients in the high-risk
group had significantly worse prognosis than patients in the low-risk group.
Univariate and multivariate Cox regression analysis showed that the two-miRNA
signature was an independent prognostic factor for the overall survival of PAAD
patients. Conclusion: Taken together, the two-miRNA signature may serve as an
accurate and sensitive biomarker for diagnosis and PAAD-outcome prediction,
facilitating the diagnosis and potentially improving treatment outcome of PAAD.
PMID- 29942154
TI - Multifocality is associated with central neck lymph node metastases in papillary
thyroid microcarcinoma.
AB - Background: This study aimed to assess the predictive factor of multifocality to
identify patients at high risk of central lymph node metastasis (CLNM). Patients
and methods: Papillary thyroid microcarcinoma patients who underwent total or
hemi-thyroidectomy with effective unilateral or bilateral central lymph node
dissection were enrolled. Results: Multifocality, age, sex, tumor size,
extrathyroidal extension, and nodular goiter were significantly associated with
CLNM. Multifocality was an independent predictor for CLNM in multivariate
analysis. Compared with unifocal disease, the odds ratio for CLNM was 1.447 for
patients with >=2 tumor foci (P<0.001) and 2.978 for patients with >=3 tumor foci
(P<0.001). The significant association is at >=3 foci diseases. Conclusion:
Multifocality with >=3 tumor foci was an independent predictive factor for CLNM
in papillary thyroid microcarcinoma. Multifocality should be assessed when
selecting patients for prophylactic central neck lymph node dissection, and we
speculate that patients with multifocality should undergo more radical treatment.
PMID- 29942153
TI - Fertility preservation in Hodgkin's lymphoma patients that undergo targeted
molecular therapies: an important step forward from the chemotherapy era.
AB - In total, 80%-90% of Hodgkin's lymphoma (HL) patients are curable with
combination chemoradiotherapy. Due to improvements in therapeutic strategies, 50%
of all relapsed/refractory patients may undergo complete clinical responses and
have long-term survival. Treatment options for HL are effective, but may have a
negative impact on post-chemotherapy fertility. Thus, cryopreservation of semen
prior to treatment is recommended for male patients. For female patients,
assisted reproductive techniques (ART) consult and fertility preservation should
be offered as a therapeutical option. In the last years, new targeted molecules
have been available for HL treatment. These new drugs showed a high rate of
overall responses in the setting of heavily pretreated patients, most of them in
relapse after autologous stem cell transplantation, a group previously considered
very poor risk. Up to 50% of patients have a complete response and an improved
overall survival. Future studies will address the usefulness of novel molecules
as a frontline therapy. Considering the high response and survival rates with
monoclonal antibody-based therapeutics, fertility has become a concerning issue
for long-term HL survivors. As progress has been made regarding ART, with the
rigorous steps planned for HL patients, more survivors will become parents.
PMID- 29942155
TI - A nomogram to predict overall survival for biliary tract cancer.
AB - Background: The aim of the study was to develop and validate a nomogram to
predict overall survival (OS) in biliary tract cancer (BTC). Patients and
methods: Patients diagnosed with BTC between 2004 and 2014 were selected for the
study from the Surveillance, Epidemiology, and End Results (SEER) database. All
patients were randomly allocated to 2 sets, the training set (n = 8,869) and the
validation set (n = 8,766), for the purposes of validation. The prognostic
effects of each variable were examined using univariate and multivariate
analyses. Cox regression models and a nomogram were developed based on
significant prognostic factors. The predictive and discriminatory capacity of the
nomogram was evaluated by Harrell's concordance index (C-index) and calibration
plots. Results: Data of 17,635 patients with BTC were collected from the SEER
database. Age; race; tumor site; tumor grade; T, N, and M stage; marital status;
and therapy were associated with survival in the multivariate models. All these
factors were integrated to construct the nomogram. The nomogram for predicting OS
displayed better discrimination power than the tumor-node-metastasis (TNM) stage
system 6th edition in the training set and validation set. The calibration curve
indicated that the nomogram was able to accurately predict 3- and 5-year OS.
Conclusion: This predictive model has the potential to provide an individualized
risk estimate of survival in patients with BTC.
PMID- 29942156
TI - Comparison of NSAIDs activity in COX-2 expressing and non-expressing 2D and 3D
pancreatic cancer cell cultures.
AB - Purpose: In this study, we evaluated the anticancer activity of non-steroidal
anti-inflammatory drugs (NSAIDs) in BxPC-3 and MIA PaCa-2 pancreatic cancer cell
cultures. Methods: To test the effect of compounds on the viability of cells, the
MTT assay was used. The activity of NSAIDs in 3D cell cultures was evaluated by
measuring the size change of spheroids. The type of cell death was identified by
cell staining with Hoechst 33342 and propidium iodide. To evaluate the effect on
the colony-forming ability of cancer cells, the clonogenic assay was used.
Results: Five out of seven tested NSAIDs reduced the viability of BxPC-3 and MIA
PaCa-2 cancer cells. Fenamates were more active against cyclooxygenase-2
expressing BxPC-3 than cyclooxygenase-2 non-expressing MIA PaCa-2 cell line.
Fenamates and coxibs exerted higher activity in monolayer cultured cells, whereas
salicylates were more active in 3D cultures. Fenamates and coxibs induced dose
dependent apoptosis and necrosis. NSAIDs also inhibited the colony-forming
ability of cancer cells. Meclofenamic acid, niflumic acid, and parecoxib
possessed higher activity on BxPC-3, and celecoxib possessed higher activity on
MIA PaCa-2 cell colony formation. Conclusion: Our results show that fenamates,
coxibs, and salicylates possess anticancer activity on human pancreatic cancer
BxPC-3 and MIA PaCa-2 cell cultures.
PMID- 29942157
TI - Expression of 4E-BP1 and phospho-4E-BP1 correlates with the prognosis of patients
with clear cell renal carcinoma.
AB - Background: Eukaryotic translation initiation factor 4E (eIF4E) is a key
regulator of protein synthesis. Changes in eIF4E activity disproportionally
affect the translation of a subset of oncogenic mRNAs in some cancers. Materials
and methods: We have assessed the expression levels of vascular endothelial
growth factor C (VEGFC), eIF4E, eIF4E-binding proteins (4E-BPs) and phospho-4E
BP1 in clear cell renal carcinoma (ccRCC; n=101) using immunohistochemistry and
analyzed the relevant mRNA levels and survival using online databases. Results:
The protein levels of VEGFC, an eIF4E-regulated gene, were upregulated in ccRCC
tissues compared with adjacent normal renal tissues, indicating an enhanced eIF4E
activity in ccRCC. The expression of eIF4E had no significant changes in ccRCC
tissues. However, 4E-BP1 and phospho-4E-BP1 were found to be overexpressed in
ccRCC tissues (P<0.05), and the high mRNA and protein levels of 4E-BP1 and
phospho-4E-BP1 correlated with an unfavorable clinical outcome in ccRCC patients.
Meanwhile, the mRNA expression of PIK3CD and PIK3CG were enhanced in ccRCC.
Conclusion: From these results, we could infer that the increase in eIF4E
activity may be caused by the increased phospho-4E-BP1 level, which was probably
due to the activation of phosphoinositide 3-kinase (PI3K) pathway.
PMID- 29942158
TI - Pheochromocytoma in Denmark during 1977-2016: validating diagnosis codes and
creating a national cohort using patterns of health registrations.
AB - Background: Pheochromocytoma and catecholamine-secreting paraganglioma (PPGL) are
rare but potentially life-threatening tumors. We aimed to validate diagnosis
codes for PPGL in the Danish National Patient Registry, the Danish National
Pathology Registry, and the Danish Registry of Causes of Death and to create a
national cohort of incident PPGL patients by linking these three registries.
Patients and methods: We obtained data from the three abovementioned registries
for all individuals registered with pheochromocytoma or catecholamine
hypersecretion in Denmark during 1977-2016 (average population 5.30 million). We
then reviewed health records for all individuals living in the North Denmark
Region and Central Denmark Region (average population 1.75 million) to validate
the diagnosis of PPGL. We tested a number of algorithms for accurately
identifying true cases of PPGL to maximize positive predictive values (PPVs) and
completeness. The best algorithm was subsequently validated in an external
sample. Results: We identified 2626 individuals with a PPGL diagnosis code in
Denmark, including 787 (30.0%) in the North Denmark Region and Central Denmark
Region. In this subsample, we retrieved the health records of 771/787 (98.0%)
individuals and confirmed 198 incident PPGL patients (25.3%). The PPV of PPGL
diagnosis codes was 21.7% in the Danish National Patient Registry, 50.0% in the
Danish Registry of Causes of Death, and 79.5% in the Danish National Pathology
Registry. By combining patterns of registrations in the three registries, we
could increase the PPV to 93.1% (95% confidence interval [CI]: 88.5-96.3) and
completeness to 88.9% (95% CI: 83.7-92.9), thus creating a national PPGL cohort
of 588 patients. PPV for the optimal algorithm was 95.3% (95% CI: 88.5-98.7) in
the external validation sample. Conclusion: Diagnosis codes for pheochromocytoma
had low PPV in several individual health registries. However, with a combination
of registries we were able to identify a near-complete national cohort of PPGL
patients in Denmark, as a valuable source for epidemiological research.
PMID- 29942159
TI - The impact of rheumatoid arthritis on the risk of adverse events following joint
replacement: a real-world cohort study.
AB - Purpose: To assess whether rheumatoid arthritis (RA) is associated with a greater
risk of adverse events following total knee replacement (TKR) and total hip
replacement (THR) than osteoarthritis (OA). Patients and methods: Individuals
with a diagnosis of RA or OA were identified using primary care records. TKR and
THR following diagnosis were identified using linked hospital records. Myocardial
infarction (MI), prosthetic joint infection (PJI), venous thromboembolism (VTE),
and death were identified within 90 days following surgery, and revision
procedures over 10 years following surgery. The impact of RA compared to OA on
the risk for these adverse events was assessed using Cox proportional hazard
models. Univariable models, with diagnosis as the only explanatory variable, and
multivariable models, with age, gender, and year of surgery first added and then
a measure of other comorbidities also included, were estimated. Results: In all
20,763 individuals, with 10,260 TKR and 10,961 THR, were included in the
analysis. Compared to those with OA, individuals with a diagnosis of RA had a
greater incidence of MI over 90 days following TKR (OA: 0.28%, RA: 0.75%) and
revision over 10 years following THR (OA: 5.55%, RA: 8.68%). Both of these
differences were statistically significant with, for example, hazard ratios of
3.54 (1.44 to 8.73) for MI and 1.61 (1.06 to 2.46) for revision after controlling
for age, gender, year of surgery, and other comorbidities. Conclusion: These
findings suggest that, compared to individuals with OA, those with RA have an
increased short-term risk of MI following TKR. While risk of MI remains below 1%,
this does underline the importance of the management of cardiovascular risk
factors for those with RA. RA was also associated with an increased long-term
risk of revision following THR, which strengthens the argument for investing in
therapies which may prevent the need for joint replacement.
PMID- 29942160
TI - Antiretroviral therapy interruptions: impact on HIV treatment and transmission.
AB - Introduction: Successful management of pediatric and adult human immunodeficiency
virus (HIV) disease includes lifelong administration of antiretroviral therapy
(ART). The need for the continuous use of antiretroviral drugs throughout the
life course poses a challenge to children, adolescents, and adults living with
HIV and their caregivers. Historically, treatment interruptions have been viewed
as a negative therapeutic strategy. Recently, however, treatment interruptions or
treatment reduction strategies have become a focus of investigations as
innovative approaches to the long-term management of HIV disease. Current
challenges with treatment interruptions include identifying an appropriate
timeframe for length of interruptions and identifying HIV patient populations in
whom the treatment interruption can be successful. Objective: In this review, we
aimed at summarizing recent studies of planned and unplanned treatment
interruptions in children and adults living with HIV. Materials and methods: We
searched two databases (PubMed and Cochrane Controlled Trials Register) using
keywords (HIV OR AIDS OR acquired immunodeficiency syndrome OR HIV-1 OR
antiretroviral) AND (treatment interruption OR planned interruption OR
therapeutic interruption OR unplanned interruption), for published randomized and
nonrandomized clinical trials and observational cohort studies in children and
adults (from birth to 99 years of age) in global settings covering a period from
2012 to 2018. In this review, only the studies that contained pediatric and
adolescent populations with baseline immunological, virological, and clinical
characteristics and outcomes after treatment interruption were included. Results:
A total of 174 eligible citations from the two databases were identified. We
identified 10 prospective treatment interruption studies on children (five
studies) and adults (five studies) during 2012-2018 with a total of 863 pediatric
and 273 adult subjects. Collectively, recent studies on children and adults with
HIV infection suggest that treatment interruptions with proper monitoring can be
successful by instituting well-defined immunological and virological parameters
or thresholds such as CD4 count, CD4%, and HIV RNA viral load that identify low
risk populations with treatment failure. In addition to standard virological and
immunological outcome measurements, selected biomarkers that help detect early
immune activation may also be useful in the monitoring of treatment interruption.
Conclusion: Treatment interruptions in adult and especially pediatric patients
with well-controlled HIV disease may provide an alternative opportunity to
optimize long-term HIV management by minimizing drug-associated toxicity and
improving long-term adherence and quality of life.
PMID- 29942161
TI - Side effect experiences of South Korean women in their twenties and thirties
after facial plastic surgery.
AB - Background: Rates of plastic surgery procedures have increased dramatically over
the past several decades, especially for the women in South Korea. Purpose: The
purpose of this study was to explore the subjective experience of South Korean
women in their twenties and thirties with facial plastic surgery (FPS) side
effects. Participants and methods: Seven women who have suffered from FPS side
effects participated in this study. Data were collected from July to September
2015 through individual in-depth interviews using open-ended questions and
analyzed using Colaizzi's method, which is a Husserlian phenomenological
approach. Results: Six themes, and 25 subthemes, were found. Major themes were
"choosing FPS to gain a new self", "facing an unintended self", "trying to accept
a changed self", "making efforts to overcome the situation", "coming to know a
new world", and "pursuing a new lifestyle". Conclusion: This study raises social
awareness on the risk of plastic surgery side effects, which could prevent
unnecessary plastic surgery. It also suggests the need for a deeper understanding
of women's biopsychosocial suffering from plastic surgery side effects.
PMID- 29942162
TI - Effectiveness of nifedipine in threatened preterm labor: a randomized trial.
AB - Objective: Threatened preterm labor is a condition in which regular uterine
contractions occur at least 1 time in 10 minutes and persist for more than 30
minutes before completion of 37 weeks of gestation without dilatation of the
cervix. In preterm labor with cervical dilatation, the efficacy of tocolytics was
proven for prolonging pregnancy. However, in threatened preterm labor, the
efficacy of tocolytics has not yet been well studied. This study aimed to
evaluate the effectiveness of nifedipine versus a placebo for inhibiting uterine
contraction in threatened preterm labor. Materials and methods: A randomized,
double-blinded, placebo-controlled study with 206 threatened preterm labor
patients was undertaken. The participants were randomly allocated into either
nifedipine or placebo groups. The proportion of patients with successful
treatment, gestational age at delivery, and neonatal outcome were compared
between the 2 groups. Results: After 90 minutes of treatment, 88.3% of the
nifedipine group and 69.9% of the placebo group had no uterine contraction
(P<0.001). Nifedipine led to successful treatment outcomes in 77.6% of the total
participants compared with 49.5% in the placebo group (P<0.001). The remainder of
the participants from both groups needed a second-line tocolytic drug. Of these,
9.7% in the nifedipine group delivered within 48 hours compared with 12.6% in the
placebo group (P>0.05). Mean gestation age at delivery and neonatal complications
for both groups were not significantly different. Conclusion: Nifedipine had a
higher success rate for inhibiting threatened preterm contractions.
PMID- 29942163
TI - Elaborated plan for incoming surgical emergency management in Sub-Saharan Africa.
AB - Background: Globally, there has been an increase in injuries as a major cause of
death. This burden is mainly due to an increase in road traffic injuries, and it
poses an enormous burden in low- and middle-income countries. Musculoskeletal and
head injuries are the most prevalent ones, which has led to an overcrowding of
traumatic surgical emergencies. Methodology: An unrestricted search was done in
different research databases for articles published in English between January
2005 and November 2017 focusing on traumatic surgical emergencies. Results: The
past several decades on the global health landscape are notable for increases in
traumatic surgical emergencies. Although this burden of surgical emergencies is
universal, high-income countries have implemented measures including mass
casualty incident management, which continuously reduces the mortality and
morbidity of trauma-related injuries. Nonindustrialized countries are facing
almost the same burden, but there is still a lack of enough sustainable measures
for combating this burden. Nevertheless, the Rwandan pre-hospital emergency care
service (SAMU) which integrate pre-hospital services, has contributed a lot in
the management of emergencies in Rwanda. Limb and head injuries are increasing,
and there is a trend that this would continue. Conclusion: A global upward shift
in traumatic surgical emergencies was noted for the past several decades. This
trend will continue, and it poses a significant burden in Sub-Saharan Africa,
along with worldwide. The Sub-Saharan African mortality and morbidity rates are
increasing in regard to traumatic surgical emergencies. Task shifting, initiation
of similar systems such as SAMU, increase in workforce, conducting enough
research, mass casualty incident protocols implementation, and zero tolerance in
regard to alcohol or psychoactive substances by road users are recommendations
from this review.
PMID- 29942164
TI - Extended Glasgow Outcome Scale correlates with bispectral index in traumatic
brain injury patients who underwent craniotomy.
AB - Background: Assessing consciousness in traumatic brain injury is important
because it also determines the treatment option, which will influence patients'
outcome. A tool used to objectively assess consciousness level is the bispectral
index (BIS) monitor, which was originally designed to monitor the depth of
anesthesia. Glasgow Outcome Scale-Extended (GOS-E) provides a measuring tool to
assess traumatic brain injury (TBI) outcome. The goal of this study was to assess
the correlation between GOS-E scores with BIS values in patients with TBI who
underwent craniotomy. Patients and methods: A total of 68 patients admitted to
the emergency department with decreased consciousness due to TBI who underwent
craniotomy were included in the study. BIS value was measured upon admission,
then GOS-E score was determined 6 months after the incident took place.
Spearman's correlation coefficient was used to assess the correlation between GOS
E score and BIS value. Results: In 68 patients, the GOS-E score was found to have
a strong correlation (r =0.921, p<0.01) with BIS values. From this study, the
formula to estimate GOS-E score based on BIS value upon admission stands as: GOS
E =0.19 (BIS) - 8.31. Conclusion: This study found that there is a strong
correlation between GOS-E score and BIS value. These findings suggest that BIS
scores upon admission may be used to predict the outcomes in patients with TBI.
However, the wide distribution of BIS values for each GOS-E score may limit the
use of BIS scores in accurately predicting GOS-E scores.
PMID- 29942165
TI - Acute pulmonary edema induced by non-ionic low-osmolar radiographic contrast
media.
AB - Background: Non-cardiogenic pulmonary edema (NCPE) after intravenous (iv)
administration of non-ionic radiocontrast media (RCM) is a rare but life
threatening complication. In a context of emergency, its diagnosis is difficult.
Case report: We report the case of a 55-year-old woman who developed an acute
pulmonary edema following iv infusion of non-ionic, low-osmolar RCM during
abdominal CT scan. She needed a 24-hour hospitalization in intensive care unit
for an acute hypoxemic dyspnea. She was falsely treated at first for an
anaphylactic reaction, and then for a cardiac failure. She improved with
cortisone and diuretic treatment. Conclusion: Although NCPE has been rarely
reported after RCM injection, it remains an acute severe complication that has to
be considered. The differential diagnosis involves multiple pathogenic patterns
giving furthermore complexity in choosing an appropriate treatment.
PMID- 29942166
TI - Influence of different soccer-specific maximal actions on physiological,
perceptual and accelerometer measurement loads.
AB - Background: The aim of this study was to compare the effect of different soccer
specific maximal actions (Continuous run, Sprint, Sprint with change of direction
[Sprint COD], Jump and Shot) upon physiological (oxygen uptake and heart rate)
and perceptual (rating of perceived exertion [RPE]) responses and accelerometer
load. Materials and methods: Ten moderately to well-trained male soccer players
volunteered to serve as subjects in this study. A repeated within-subject design
was used in which each subject was tested on five occasions on different days,
one test each day, during a period of 2 weeks. Each of the five tests had a
distance of 900 m and lasted 5 minutes, thus the mean speed for all five tests
was 3 m/s. During the test, oxygen uptake, heart rate and accelerometer load were
measured. Immediately after each test, RPE was recorded, and after the test,
oxygen uptake was measured for 5 minutes while the subject sat in an upright
position on a chair. Results: In the comparison of different soccer-specific
maximal actions upon physiological and perceptual responses and accelerometer
load, this study found that the total accelerometer load was lowest in Sprint and
Sprint COD conditions, although the physiological (oxygen uptake and heart rate)
and perceptual (RPE) responses were highest in the respective conditions. The
Jump condition experienced lower RPE than Sprint and Sprint COD but achieved the
highest accelerometer load. Conclusion: Accelerometer load is not a valid
measurement for energy costs or RPE but may function as a complementary tool to
investigate the player loads during matches and training.
PMID- 29942167
TI - Impact of systemic juvenile idiopathic arthritis/Still's disease on adolescents
as evidenced through social media posts.
AB - Purpose: To understand the experience of adolescent systemic juvenile idiopathic
arthritis (SJIA) patients and those of their parents based on their social media
posts. Methods: English language posts related to SJIA, Still's disease, or
juvenile arthritis were collected and analyzed. Results: In total, 71 posts
created between 2009 and 2015 on 15 websites were identified in November 2015. Of
the 32 unique authors, 17 were SJIA patients aged 13-20 years (40 posts), 7 were
mothers of SJIA patients (12 posts), and 8 patients had unspecified forms of
juvenile arthritis (19 posts). Many patients posted about similar diagnostic
experiences marked by 5 phases: 1) early prediagnosis: pain and fatigue
overlooked until crisis occurred, 2) first misdiagnosis: doctors talked about
"growing pains" and psychosocial problems ("fake pains" to avoid school), 3)
second misdiagnosis: severity acknowledged, but diagnosed as leukemia or another
cancer, 4) tests: tests leading to diagnosis and treatment conducted, and 5)
cognitive identity: patient accepted the diagnosis and its implications. Many
adolescent patients, looking back at disease onset in their childhood, described
themselves as a "sleeping child" rather than the typical active child. Several
patients tried to hide their illness from friends, but expressed concerns openly
online. Many patients described SJIA as a powerful external enemy, using terms
like "bulldozer," "dragon," and "monster." Many posts from patients and their
mothers used superhero language/imagery to help "fight" SJIA. Some patients also
posted about the risk of death. Conclusion: Although most adolescent SJIA
patients openly posted about the difficulties of their disease online, they made
efforts to hide their disease in the real world. They frequently used superhero
words and images in describing their fight for better health. Physicians can use
these insights when counseling SJIA patients to provide a narrative that meshes
with the patients' worldview and perhaps to improve physician-patient
communication to increase treatment adherence.
PMID- 29942168
TI - Use of blood biomarkers to screen for obstructive sleep apnea.
AB - Purpose: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated
with increased risk for cardiovascular disease, diabetes, and other chronic
conditions. Unfortunately, up to 90% of individuals with OSA remain without a
diagnosis or therapy. We assess the relationship between OSA and blood
biomarkers, and test the hypothesis that combinations of markers provide a
characteristic OSA signature with diagnostic screening value. This validation
study was conducted in an independent cohort in order to replicate findings from
a prior feasibility study. Patients and methods: This multicenter prospective
study consecutively enrolled adult male subjects with clinically suspected OSA.
All subjects underwent overnight sleep studies. An asymptomatic control group was
also obtained. Five biomarkers were tested: glycated hemoglobin (HbA1c), C
reactive protein (CRP), uric acid, erythropoietin (EPO), and interleukin-6 (IL
6). Results: The study enrolled 264 subjects. The combination of HbA1c+CRP+EPO
(area under the curve 0.78) was superior to the Epworth Sleepiness Scale (ESS;
0.53) and STOP-Bang (0.70) questionnaires. In non-obese subjects, the combination
of biomarkers (0.75) was superior to body mass index (BMI; 0.61). Sensitivity and
specificity results, respectively, were: HbA1c+CRP+EPO (81% and 60%), ESS (78%
and 19%), STOP-Bang (75% and 52%), BMI (81% and 56%), and BMI in non-obese
patients (81% and 38%). Conclusion: We verify our hypothesis and replicate our
prior feasibility findings that OSA is associated with a characteristic signature
cluster of biomarker changes in men. Concurrent elevations of HbA1c, CRP, and EPO
levels should generate a high suspicion of OSA and may have utility as an OSA
screening tool. Biomarker combinations correlate with OSA severity and,
therefore, may assist sleep centers in identifying and triaging higher risk
patients for sleep study diagnosis and treatment.
PMID- 29942169
TI - Sleeping tongue: current perspectives of genioglossus control in healthy
individuals and patients with obstructive sleep apnea.
AB - The focus of this review was on the genioglossus (GG) muscle and its role in
maintaining upper airway patency in both healthy individuals and obstructive
sleep apnea (OSA) patients. This review provided an overview of GG anatomy and GG
control and function during both wakefulness and sleep in healthy individuals and
in those with OSA. We reviewed evidence for the role of the GG in OSA
pathogenesis and also highlighted abnormalities in GG morphology, responsiveness,
tissue movement patterns and neurogenic control that may contribute to or result
from OSA. We summarized the different methods for improving GG function and/or
activity in OSA and their efficacy. In addition, we discussed the possibility
that assessing the synergistic activation of multiple upper airway dilator
muscles may provide greater insight into upper airway function and OSA
pathogenesis, rather than assessing the GG in isolation.
PMID- 29942170
TI - Perceptions and attitudes toward clinical trials in adolescent and young adults
with cancer: a systematic review.
AB - Purpose: Although cancer clinical trials (CT) offer opportunities for novel
treatments that may lead to improved outcomes, adolescents and young adults (AYA)
are less likely to participate in these trials as compared to younger children
and older adults. We aimed to identify the perceptions and attitudes toward CT in
AYA that influence trial participation. Materials and methods: A systematic
review of cancer literature was conducted that assessed perceptions and attitudes
toward CT enrollment limited to AYA patients (defined as age 15-39). We estimated
the frequency of identified themes by pooling identified studies. Results: In
total, six original research articles were identified that specifically addressed
perceptions or attitudes that influenced CT participation in AYA patients. Three
studies were conducted at pediatric centers - one at an AYA unit, one at an adult
cancer hospital, and one was registry based. Major themes identified for CT
acceptability included: hope for positive clinical affect, altruism, and having
autonomy. Potential deterrents included: prolonged hospitalization, worry of side
effects, and discomfort with experimentation. Conclusion: Limited information is
available with regard to the perceptions and attitudes toward CT acceptability
among AYA patients, especially those treated at adult cancer centers, which
prevents generalization of data and themes. Future research assessing strategies
for understanding and supporting CT decision-making processes among AYA
represents a key focus for future funding to improve CT enrollment.
PMID- 29942171
TI - Does the perception of severity of medical error differ between varying levels of
clinical seniority?
AB - Background and purpose: The Francis Report called for a more "open culture" to
empower health care staff to report medical errors. However, there are differing
opinions amongst doctors as to what constitutes a medical error, and no previous
study has investigated whether the perception of medical errors varies with
clinical seniority. Methods: A prospective study comprising medical students (s),
junior doctors (jd), and consultants (c) from one Deanery was conducted, where
participants were anonymously assessed on their perceptions of error in eight
different hypothetical scenarios using a numerical scale (1-10). Scenarios were
reviewed for face validity and pilot tested before implementation. A statistician
prospectively determined the number of participants to ensure the study was
sufficiently powerful. Scenario ratings were analyzed using non-parametric
statistical tests and free-text answers were analyzed by immersion and
crystallization. Results: Two hundred thirteen participants were recruited with
near equal distribution in gender (51%:49%, F:M) and clinical seniority
(36%:34%:30%, s:jd:c, respectively). Significant difference was shown in three
out of the eight scenarios between the students and the consultants, and in one
of those three between junior doctors and students. Qualitative analysis found
various factors that contribute to participants' decision regarding error
severity. Students and junior doctors commented on potential consequences in
greater detail, but consultants showed greater awareness of the latent factors
contributing to error. Conclusion: Heterogeneity in answers was seen within each
of the cohorts. The most influential factors were scenario outcome and potential
consequences. Latent factors, such as error circumstances and participant's
empathy, also contributed to response. There were significant differences in the
scores between medical students and consultants in some scenarios which may be
related to clinical experience. The heterogeneity of answers suggests there is
scope for improvement in medical error education.
PMID- 29942172
TI - Systematics of South American snail-eating snakes (Serpentes, Dipsadini), with
the description of five new species from Ecuador and Peru.
AB - A molecular phylogeny of the Neotropical snail-eating snakes (tribe Dipsadini) is
presented including 43 (24 for the first time) of the 77 species, sampled for
both nuclear and mitochondrial genes. Morphological and phylogenetic support was
found for four new species of Dipsas and one of Sibon, which are described here
based on their unique combination of molecular, meristic, and color pattern
characteristics. Sibynomorphus is designated as a junior subjective synonym of
Dipsas. Dipsas latifrontalis and D. palmeri are resurrected from the synonymy of
D. peruana. Dipsas latifasciata is transferred from the synonymy of D. peruana to
the synonymy of D. palmeri. A new name, D. jamespetersi, is erected for the taxon
currently known as Sibynomorphus petersi. Re-descriptions of D. latifrontalis and
D. peruana are presented, as well as the first photographic voucher of an adult
specimen of D. latifrontalis, along with photographs of all known Ecuadorian
Dipsadini species. The first country record of D. variegata in Ecuador is
provided and D. oligozonata removed from the list of Peruvian herpetofauna. With
these changes, the number of Dipsadini reported in Ecuador increases to 22, 18
species of Dipsas and four of Sibon.
PMID- 29942173
TI - An updated checklist of the Tenebrionidae sec. Bousquet et al. 2018 of the
Algodones Dunes of California, with comments on checklist data practices.
AB - Generating regional checklists for insects is frequently based on combining data
sources ranging from literature and expert assertions that merely imply the
existence of an occurrence to aggregated, standard-compliant data of uniquely
identified specimens. The increasing diversity of data sources also means that
checklist authors are faced with new responsibilities, effectively acting as
filterers to select and utilize an expert-validated subset of all available data.
Authors are also faced with the technical obstacle to bring more occurrences into
Darwin Core-based data aggregation, even if the corresponding specimens belong to
external institutions. We illustrate these issues based on a partial update of
the Kimsey et al. 2017 checklist of darkling beetles - Tenebrionidae sec.
Bousquet et al. 2018 - inhabiting the Algodones Dunes of California. Our update
entails 54 species-level concepts for this group and region, of which 31 concepts
were found to be represented in three specimen-data aggregator portals, based on
our interpretations of the aggregators' data. We reassess the distributions and
biogeographic affinities of these species, focusing on taxa that are precinctive
(highly geographically restricted) to the Lower Colorado River Valley in the
context of recent dune formation from the Colorado River. Throughout, we apply
taxonomic concept labels (taxonomic name according to source) to contextualize
preferred name usages, but also show that the identification data of aggregated
occurrences are very rarely well-contextualized or annotated. Doing so is a pre
requisite for publishing open, dynamic checklist versions that finely accredit
incremental expert efforts spent to improve the quality of checklists and
aggregated occurrence data.
PMID- 29942174
TI - Cryptic species of Curvularia in the culture collection of the Queensland Plant
Pathology Herbarium.
AB - Several unidentified specimens of Curvularia deposited in the Queensland Plant
Pathology Herbarium were re-examined. Phylogenetic analyses based on sequence
data of the internal transcribed spacer region, partial fragments of the
glyceraldehyde-3-phosphate dehydrogenase and the translation elongation factor 1
alpha genes, supported the introduction of 13 novel Curvularia species. Eight of
the species described, namely, C. beasleyisp. nov., C. beerburrumensissp. nov.,
C. eragrosticolasp. nov., C. kenpeggiisp. nov., C. mebaldsiisp. nov., C.
petersoniisp. nov., C. platziisp. nov. and C. warraberensissp. nov., were
isolated from grasses (Poaceae) exotic to Australia. Only two species, C.
lamingtonensissp. nov. and C. sporobolicolasp. nov., were described from native
Australian grasses. Two species were described from hosts in other families,
namely, C. coatesiaesp. nov. from Litchi chinensis (Sapindaceae) and C.
colbraniisp. nov. from Crinum zeylanicum (Amaryllidaceae). Curvularia reesiisp.
nov. was described from an isolate obtained from an air sample. Furthermore, DNA
sequences from ex-type cultures supported the generic placement of C. neoindica
and the transfer of Drechslera boeremae to Curvularia.
PMID- 29942175
TI - Knowledge and practice regarding contact lens among Saudi urban contact lens
users.
AB - Purpose: To assess the level and determinants of knowledge and practice regarding
contact lens (CL) and its accessories among adult Saudi CL users. Methods: This
survey was conducted in 2015 for Saudi contact lens users visiting a Mall in
Riyadh, Saudi Arabia. The questions were related to knowledge about contact
lenses, correct CL and accessories usage. We inquired indication, initial
prescription, CL use, complications experienced and their management. The
knowledge and practice responses were correlated to their determinants. Results:
In this survey, 510 contact lens users participated. The level of knowledge was
of excellent grade among 279 [54.7% (95% Confidence Interval 50.4-59)] CL users.
The practice was of excellent grade in 210 [41.4% (95% CI 37.1-45.7)] CL users.
Variation in knowledge was not associated to gender (P = 0.1), education (P =
0.4), type of work (P = 0.3), funding for CL (P = 0.1). Occasional users and
those not having prescribed CL had significantly poor knowledge (P < 0.001). The
excellent level of practice was associated to younger CL users (P = 0.004). While
it was not associated to gender (P = 0.8), type of CL (P = 0.9), funding for CL
(P = 0.2), education (P = 0.7) and occupation (P = 0.1). Conclusions: The
knowledge and practice among CL users was less than desired. Those using contact
lens for cosmetic purpose and procuring them without prescription need special
focus for health promotion so that their CL related practice improve and eye
complications are reduced.
PMID- 29942176
TI - Comparison between corneal cross-linking, topical antibiotic and combined therapy
in experimental bacterial keratitis model.
AB - Purpose: This study was conducted to investigate the effects of an experimental
bacterial keratitis model on the corneal collagen cross-linking treatment (CXL),
and also to compare topical antibiotic treatment with the combined treatment.
Methods: The study involved 40 young adult female Sprague Dawley rats, which had
a 2 mm scraped defect of the central corneal epithelium in both eyes. The rats
were divided into two equal groups. The first group was inoculated in both eyes
with standard Pseudomonas Aeruginosa (PA) from a strain suspension prepared from
0.05 ml (Group 1), and the second group was inoculated with standard Methicillin
Resistance Staphylococcus Aureus (MRSA) strains from a suspension prepared from
0.05 ml (Group 2). Group 1 was divided into four sub-groups: Group 1A was treated
by collagen cross-linking (CXL), Group 1C was treated with topical tobramycin
drops CXL and also treated by collagen cross-linking (CXL), Group 1D was treated
with topical tobramycin drops, and Group 1B was left untreated in order to create
a control group. Similarly, Group 2 was also divided into four sub-groups: Group
2A was treated by CXL, Group 2C was treated with topical 5% fortified vancomycin
drops CXL and also treated by CXL, Group 2D was treated with topical 5% fortified
vancomycin drops, and Group 2B was left untreated in order to create a control
group. CXL was performed on the third day following the inoculation and topical
drop therapy. Biomicroscopy and microbiologic assessments were performed on the
third and seventh days following the inoculation of microorganisms. Results: In
the treatment, which compared baselines in all groups before treatment, the
diameter of keratitis infiltrations, corneal clouding, and corneal swab samples
were obtained from the reduction in reproduction. The results were statistically
significant (p < 0.01). Keratitis infiltration groups were conducted on the
seventh day for Groups 1C and 1D according to Group 1B, whilst Groups 2A, 2C and
2D were conducted according to Group 2B, which showed a significant statistical
reduction (p < 0.01). On the seventh day, focal groups were conducted in corneal
clouding Group 1D according to Group 1B and in Groups 2A, 2C and 2D according to
Group 2B, which revealed a significant statistical reduction (p < 0.01). On the
seventh day, reproduction in culture was obtained from corneal swab samples in
Groups 1C and 1D according to Group 1B; in Groups 1C and 1D according to Group
1A; in Groups 2A, 2C and 2D according to Group 2B; and in Group 2C according to
Group 2A, where a significant statistical reduction was observed (p < 0.01).
Conclusions: The clinical and microbiological efficacy of the CXL treatment is
evaluated in our study. In accordance with the conclusion reached an effective
reduction in the density and severity of (infection), occurred as a result of CXL
treatment, CXL treatment combined with topical antibiotic treatment and topical
antibiotic treatment of Pseudomonas Aeruginosa (PA) and Metisilin Rezistant
Staphylococcus Aureus (MRSA) keratitis infections. From these results, it is
shown that topical antibiotics and CXL potentiate each other's effects in the
treatment of resistant bacterial keratitis.
PMID- 29942177
TI - Management of traumatic corneal abrasion by a sample of practicing
ophthalmologists in Saudi Arabia.
AB - Purpose: Corneal epithelial defect (CED) is a common medical emergency condition
involving loss of surface epithelial layer of the cornea. The aim of the study is
to explore the practice patterns of ophthalmologists in management of traumatic
CED in Saudi Arabia and to assess the variance in clinical practice from the
established clinical practice guidelines. Methods: A Survey based study at King
Abdulaziz University Hospital between March 2015 and January 2016. A survey of 16
relevant closed ended questions was distributed to 300 practicing
ophthalmologists including Saudi Ophthalmology Society (SOS) members and non
members. The survey questionnaire focused on the known aspects of traumatic CED
management. Results: 188 practicing ophthalmologists responded to the distributed
questionnaire. That represents a 63% response rate for the present survey study.
The age group most commonly affected by traumatic CED is 6-18 years old (61.2%).
Fingernail trauma (n = 129, 68.6%) was the major cause of CED reported by
respondents. In large CED (>5 mm) most common modality of treatment is pressure
patching with topical antibiotics with or without cycloplegics (40.4%) whereas in
small CED (<2 mm) topical antibiotics and cycloplegics is the preferred way
(40.4%). The most commonly used prophylactic antibiotic was second-generation
fluroquinolons (58.5%). Conclusions: Present study demonstrates that practicing
ophthalmologists are reporting that traumatic CED mostly affects young people and
fingernail trauma is the major cause. There is lack of clear institutional
guidelines and consensus on the management of traumatic corneal abrasions.
PMID- 29942178
TI - Comparison of conjunctival autograft and conjunctival transposition flap
techniques in primary pterygium surgery.
AB - Purpose: To investigate and compare the efficacy of conjunctival autograft and
conjunctival transpositional flap for the treatment of primary pterygium surgery.
Design: Retrospective, interventional case series analysis. Materials and
methods: Medical records of 48 patients who underwent pterygium surgery by
conjunctival autograft or conjunctival transpositional graft for primary
pterygium surgery were reviewed. The conjunctival defects after pterygium
excision were repaired in 21 eyes with conjunctival autograft and in 27 eyes with
conjunctival transpositional flaps. All operations were performed under
subconjunctival anesthesia using 8.0 vicryl sutures. Two groups were compared in
terms of pterygium size, surgery time, complications and pterygium recurrence.
Results: Mean pterygium size was 2.8 mm in conjunctival transpositional flap
group, and 3.4 mm in conjunctival autograft group (p < 0.01). Mean surgery time
in conjunctival transpositional flap and conjunctival autograft groups was 15.9
and 21.7 min, respectively. The haematoma formation under the graft was observed
postoperatively in one eye of conjunctival autograft group. The only one case of
recurrence was observed in both conjunctival autograft and conjunctival
transpositional flap groups (3.7% and 4.7%, respectively). Mean follow up time
was 11.78 months in conjunctival transpositional flap group and 14.95 months in
conjunctival autografting group (p < 0.01). Conclusion: Both conjunctival
transpositional flap and conjunctival autograft techniques have same results in
terms of pterygium recurrence and surgery complications in the treatment of
primary pterygium. Surgery time in conjunctival transpositional flap technique is
significantly shorter. Conjunctival transpositional flap technique may be a good
alternative method for primary pterygium surgery.
PMID- 29942179
TI - Prevalence of keratoconus among patients seeking laser vision correction in Taif
area of Saudi Arabia.
AB - Purpose: To determine the prevalence of keratoconus among patients seeking laser
vision correction (LVC). Methods: Retrospective study of 1374 eyes of 687
patients (335 males, 352 females) who underwent keratoconus screening as a part
of routine preoperative evaluation prior to LVC at the Tadawi surgical centre,
Taif, Saudi Arabia from January 2014 to June 2015. The diagnosis of keratoconus
was based on evaluation of Pentacam derived parameters. Results: Manifest
keratoconus was found in 59 subjects (out of 687 subjects) representing a
prevalence rate of 8.59%. Of the 687 subjects, 45 subjects (6.55%) had bilateral
manifest keratoconus (manifest keratoconus in both eyes or manifest keratoconus
in one eyes and sub-clinical in contralateral eye) and remaining 14 patients
(2.04%) had unilateral manifest keratoconus (with normal fellow eye). Sub
clinical keratoconus was diagnosed in 65 patients representing a prevalence rate
of 9.46%. Of the 687 patients, 20 cases (2.91%) with subclinical keratoconus were
bilateral and 45 (6.55%) were unilateral. Overall, 19.70% males (66/335) and
16.48% (58/352) females had either manifest or sub-clinical keratoconus,
representing no statistically significant difference in the gender predisposition
of the keratoconus disease process (Chi Square test; p = .277). Conclusion: High
prevalence of keratoconus was found among patients seeking LVC. Possible factors
contributing to the high prevalence were recognized to be highly selective
population (patients seeking LVC for myopia/hyperopia/astigmatism), ethnicity
(high prevalence of consanguinity) and geographical location (high altitude) of
the study subjects.
PMID- 29942180
TI - Severe retinal degeneration at an early age in Usher syndrome type 1B associated
with homozygous splice site mutations in MYO7A gene.
AB - Purpose: Usher syndrome is the most common cause of deafness associated with
visual loss of a genetic origin. The purpose of this paper is to report very
severe phenotypic features of type 1B Usher syndrome in a Saudi family affected
by positive homozygous splice site mutation in MYO7A gene. Methods: Affected
siblings went through detailed history. Complete ophthalmic examination was done.
Imaging with colour fundus photography, fundus autofluorescence (AF), and optical
coherence tomography (OCT) scans was performed. Full field electroretinogram
(ffERG) was recorded. Molecular genetic testing was done using next-generation
sequencing. Results: Visual acuity was more reduced (range 20/300-20/40) in older
siblings (age>30 years), than in younger (age <30 years) siblings (range 20/70
20/25). OCT scans showed macular atrophy in all but one case that has cystoid
macular edema (CME). AF demonstrated atrophy outside a small foveal area showing
high signal. FfERG was flat in all cases. The homozygous splice site mutation
c.470+1G>A in intron 5 of the MYO7A gene was detected in all affected siblings.
Conclusions: This mutation manifested with advanced retinal degeneration at a
young age. This may have implications regarding future gene therapy in Usher
syndrome cases with this genotype.
PMID- 29942182
TI - Characteristics, management, and outcome of patients with uveal melanoma treated
by Iodine-125 radioactive plaque therapy in a single tertiary cancer center in
Jordan.
AB - Objective: To evaluate King Hussein Cancer Center experience in using Iodine-125
COMS radioactive plaque for treatment of Uveal Melanoma in Jordan. Methods:
Retrospective case series of eyes with uveal melanoma treated by Iodine-125 COMS
radioactive plaque therapy. Data collection required access to medical,
radiology, Labs and pathology reports. Main outcomes studied includes:
Demographics, tumor features, eye salvage, visual outcome, metastasis, and
mortality. Results: Between September 2008 and March 2015, 28 eyes for 28
patients had intraocular uveal melanoma and treated by Iodine-125 radioactive
plaque therapy. The mean age at diagnosis was 48 years and 16(57%) were males.
The mean tumor thickness was 8 mm (range: 4-13 mm), and 27(96%) patients had
medium or large size tumor. The radioactive plaques used had a median size of 16
mm (range: 12-20 mm). The mean apical dose was 83.5 Gy (range 81-87 Gy), and the
median radiation rate was 7.25 (range: 4.5-13). At median follow up of 2 years
(range 0.5-7 years), eye salvage rate was 93%. Four (15%) patients had distance
metastasis, and 3(11%) were dead. Fifty percent of patient had visual acuity
better than 20/200 at the last date of follow up. Conclusion: Our preliminary
results are encouraging and are comparable to another countries worldwide. The
use of Iodine-125 COMs plaque therapy at the inspection of implementation of
plaque therapy in the developing countries can lead to eye salvage in more than
90% of cases, and reserves functional vision in more than 50% of cases.
PMID- 29942181
TI - Assessment of the macula and choroid in pediatric keratoconus patients.
AB - Purpose: To present choroidal and macular thickness measurements in pediatric
patients with keratoconus and to evaluate a possible correlation between anterior
and posterior segment parameters. Methods: 50 eyes of 50 patients and 50 eyes of
50 age-matched controls were included in this cross-sectional comparative study.
The participants underwent ophthalmologic examination including; refraction,
visual acuity, biomicroscopy, corneal topography and optical coherence
tomography. The choroidal thickness (CT) was measured at subfoveal area and at
500 microns intervals to the nasal and temporal to the fovea up to 1500 microns.
Results: The mean age of the patients and controls were 12.4 +/- 1.9 and 12.0 +/-
2.1 years. The mean thinnest corneal pachimetry was 456 +/- 57 MUm, the mean
central macular thickness (CMT) was 258 +/- 24 MUm and the mean subfoveal
choroidal thickness was 342 +/- 30 MUm for the patients. There was no significant
difference between the patients and controls in regards of CMT and CT at any
measured points (p > 0.05 for all). There was no correlation between anterior
segment parameters and CMT. There was no correlation between anterior segment
parameters and subfoveal choroidal thickness. Conclusions: We may conclude that
keratoconus does not affect the CMT and CT of pediatric keratoconus patients, and
we may propose that we do not need a correction for this group of patients when
we need to evaluate the CMT and CT.
PMID- 29942183
TI - Low vision rehabilitation: An update.
AB - This article provides information concerning issues related to the care of
individuals who are visually impaired. Issues reviewed include determining who
should be referred for vision rehabilitation services, Charles Bonnet syndrome,
visual acuity, contrast sensitivity and visual field testing along with Useful
Field of View testing. This article also discusses technology advances that can
enhance the visual functioning of individuals who are visually impaired,
including how these advances can help drivers with visual impairments to continue
to safely operate motor vehicles, at least on a limited basis. Finally, resources
that are available to both encourage and motivate patients to take advantages of
vision rehabilitation services are reviewed.
PMID- 29942184
TI - Review of the treatment of Graves' ophthalmopathy: The role of the new radiation
techniques.
AB - Graves ophthalmopathy (GO) is an autoimmune disorder and the most frequent
extrathyroidal manifestation of Graves' disease. GO is an inflammatory process
leading to an increased volume of the extraocular muscles and orbital connective
and adipose tissues associated with multiple histopathological changes. Despite
recent progress in the understanding of its pathogenesis, GO often remains a
major diagnostic and therapeutic challenge. It has become increasingly important
to classify patients into categories based on disease severity and activity. Low
doses of radiotherapy (RT) have demonstrated a benefit in the treatment of
moderate-to-severe GO with very few side effects. New RT techniques deliver a
more conformal dose distribution to the target and decrease the dose to normal
healthy tissue minimizing the risk of side effects. In this review we briefly
analyzed the pathogenesis of GO and discussed the most relevant therapeutic
approaches, with particular emphasis in the new RT technics. Appropriately
designed and powered clinical studies are necessary to determine the most
effective treatment with the lowest risk of side effects.
PMID- 29942185
TI - Favorable outcome after choroidal drainage for postoperative kissing
suprachoroidal hemorrhage following trabeculectomy in a high myopic vitrectomised
eye.
AB - A 39-year-old lady with past history of vitreoretinal surgery for retinal
detachment and cataract surgery with Intraocular lens implantation was diagnosed
as uncontrolled glaucoma. She had high myopia. She underwent Trabeculectomy and
following which she presented with massive suprachoroidal hemorrhage in the first
postoperative day with severe loss of vision. This case depicts the risk of
suprachoroidal hemorrhage in a high myopic vitrectomised eye following glaucoma
filtration surgery. It also demonstrates a favorable outcome following
intervention for postoperative Suprachoroidal hemorrhage. At present, there is no
evidence in literature of such event in a high myopic Vitrectomised eye following
Trabeculectomy.
PMID- 29942186
TI - Clinical presentation of multiple cerebral emboli and central retinal artery
occlusion (CRAO) as signs of cardiac myxoma.
AB - Cardiac myxomas are benign tumors of endocardial origin that usually occur in the
left atrium. Trans-thoracic echocardiography is the diagnostic method of choice,
and early surgical removal is the preferred method of treatment. We present a
patient whose history of cerebral emboli and central retinal artery occlusion
(CRAO) led to a diagnosis of cardiac myxoma. Neuroimaging studies showed multiple
infarcts in the region of the left middle and anterior cerebral arteries.
Ophthalmic examination showed gross retinal pallor compatible with left central
retinal artery occlusion (CRAO). The etiology of stroke was investigated by
performing trans-thoracic echocardiography, which showed a mass in the left
atrium compatible with cardiac myxoma. Complete removal of the cardiac tumor was
performed by open-heart surgery. Fortunately, after a period of rehabilitation,
the patient's hemiparesis almost completely resolved, but the loss of vision OS
remained unchanged. Many cases of myxoma are accompanied by constitutional
symptoms, such as anemia, fever and weight loss, which allow for a diagnosis to
made before serious complications such as embolism occur. Unfortunately, in some
patients, such as ours, the absence of signs and symptoms allows the myxoma to
pass completely unnoticed until the first embolic event occurs.
PMID- 29942187
TI - Conjunctival melanoma in a child: A clinicopathological report.
AB - We report a case of a 16 years old Asian Indian boy who presented with a large
brownish lesion measuring 20 * 12 mm on the temporal conjunctive in his right
eye. Anterior segment optical coherence topography revealed cystic spaces without
scleral involvement. The patient underwent conjunctival excisional biopsy using
"no touch" technique with double freeze-thaw cryotherapy to underside of the
adjacent conjunctival margins. Excision involved 4 mm of the surrounding
apparently normal conjunctiva. Absolute alcohol epitheliectomy was done at the
limbus and surrounding 2 mm of cornea to devitalize residual atypical melanocytes
if any. Histopathology confirmed diagnosis of conjunctival melanoma. We started
the patient on topical mitomycin C 0.04% with one weekly on and off cycles
postoperatively. No recurrence was noted after nine months follow up.
PMID- 29942188
TI - Fungal keratitis caused by a rare ocular pathogen, Gjaerumia minor: A case
report.
AB - Fungal keratitis is an important infection of the eye that may cause devastating
effects. Keratitis caused by fungi has been described in many parts of the world
mainly in tropical countries. The objective of this study is to report a serious
eye infection in an adult with a known history of diabetes caused by an uncommon
yeast fungus with details of clinical findings and laboratory investigations.
Left eye visual acuity was no perception of light due to end stage neovascular
glaucoma. The patient was pseudophakic in both eyes. Culture of a corneal
scraping showed yeast like organism on Sabouraud dextrose agar. Gjaerumia minor,
a rare yeast but with history of a pulmonary infection in the region, was
confirmed with 98% similarity in the large subunit ribosomal RNA gene (accession
KY690175). Topical Amphotericin B and oral fluconazole were initiated. The
patient showed gradual improvement, epithelial defect healed, infiltration
steadily regressed and hypopyon disappeared. We report the first case of fungal
keratitis caused by G. minor in Saudi Arabia. Fungal Keratitis should be
considered in cases where clinical response to the conventional antibacterial
antibiotic treatment is not optimal.
PMID- 29942189
TI - Herpetic ocular manifestations in a patient with GATA2 deficiency.
AB - Specific genetic deficiencies are a rare cause that should be included in the
diagnostic algorithm of disseminated herpetic lesions. The aim of this article is
to describe the ocular herpetic manifestations in a rare genetic disorder called
GATA2 deficiency. We present the clinical case of a 26-year-old male with
dendritic ulcers in his cornea, marrow aplasia and idiopathic chronic lymphedema.
He was diagnosed with GATA2 deficiency. GATA2 gene is critical for the genesis
and function of hematopoietic stem cells. Its deficiency can cause
myelodysplastic syndromes, congenital lymphedema and severe viral infections. Our
patient presented these three manifestations, added to a deletion in 20q12 that
confirmed the suspicion of GATA2 mutation. A bone marrow transplant was suggested
as definitive treatment. The corneal herpetic epithelial lesion was analogous to
a regular hepetic keratitis with none stromal keratitis.
PMID- 29942190
TI - Uveitis and internuclear ophthalmoplegia as ocular manifestations of sarcoidosis.
AB - Sarcoidosis is a multisystemic granulomatous chronic disease of unknown etiology
with a wide range of clinical presentations. Diagnosis of sarcoidosis in patients
with ocular manifestations can be challenging. We first describe a case of
sarcoidosis presented with pulmonary involvement and both uveitis and
internuclear ophthalmoplegia as ocular manifestations. A 55-year-old caucasian
woman with non-productive cough and weakness presented with bilateral
granulomatous anterior uveitis. Few days later, the patient presented again
complaining of horizontal diplopia due to internuclear ophthalmoplegia. The
diagnosis of sarcoidosis was made as a result of clinical examination and
systemic investigations. Particularly, high-resolution computed tomography
scanning of the chest was able to identify bilateral hilar lymphadenopathy not
previously detected by chest X-ray. Biopsy confirmed diagnosis showing classic
non-caseating granulomas.
PMID- 29942191
TI - Unilateral macular chorioretinitis in subacute sclerosing panencephalitis studied
by spectral domain optical coherence tomography.
PMID- 29942192
TI - Frequency of mitochondrial m.1555A > G mutation in Syrian patients with non
syndromic hearing impairment.
AB - Background: Mitochondrial maternally inherited hearing impairment (HI) appears to
be increasing in frequency. The incidence of mitochondrial defects causing HI is
estimated to be between 6 and 33% of all hearing deficiencies. Mitochondrial
m.1555A > G mutation is the first mtDNA mutation associated with non-syndromic
sensorineural deafness and also with aminoglycoside induced HI. Its prevalence
varied geographically between different populations. Methods: We carried out PCR,
restriction enzyme based screening, and sequencing of 337 subjects (including 132
patients diagnosed clinically with hereditary deafness) from 54 families from
Syria for m.1555A > G mitochondrial mutation. Results: Mitochondrial m.1555A > G
mutation was detected in one of fifty-four families (1.85%), six out of the 132
(4.5%) of all patients with NSHI and one propositus of the 205 individuals with
normal hearing (0.48%). Conclusion: This is the first study to report prelingual
deafness causative gene mutations identified by sequencing technology in Syrian
families. It is obvious from the results that the testing for the m.1555A > G
mutation is useful for diagnosis of hearing loss in Syrian patients and should
also be considered prior to treatment with aminoglycosides in predisposed
individuals.
PMID- 29942193
TI - The role of bile acids in cellular invasiveness of gastric cancer.
AB - Background: Bile acids have been implicated in the development of digestive tract
malignancy by epidemiological, clinical and animal studies. The growth and
transformation signaling by most of the bile acids is thought to be related to
the induced cyclooxygenase-2 (COX-2) expression and increased production of
prostaglandin E2 (PGE2). The highly hydrophobic bile acids such as
chenodeoxycholic acid (CD) and deoxycholic acid can promote carcinogenesis and
stimulate the invasion of colon cancer cells. On the contrary, ursodeoxycholic
acid (UDCA), a less hydrophobic stereoisomer of CD, inhibits proliferation and
induces apoptosis in colon cancer cells. We examined the effects of bile acid on
human gastric cancer cells MKN-74. Methods: Early-passage human gastric cancer
MKN-74 cells were used for drug treatment, preparation of whole cell lysates,
subcellular extracts and Western blot analysis. The levels of PGE2 released by
the cells were measured by enzyme inummoassay to indicate COX-2 enzymatic
activity. Cellular invasion assay was performed in Boyden chamber. Results:
Exposure of CD led to activation of protein kinase C (PKC) alpha, increased COX-2
expression and increased PGE2 synthesis. The induced COX-2 protein expression
could be detected within 4 h exposure of 200 MUM CD, and it was dose- and time
dependent. PGE2 is the product of COX-2, and has been reported to cause tumor
invasion and angiogenesis in animal study. Safingol (SAF), a PKC inhibitor,
suppressed the COX-2 protein expression and PGE2 production by CD in MKN-74.
Furthermore, UDCA suppressed PGE2 production by CD but did not affect COX-2
protein expression induced by CD. Using a Boyden chamber invasion assay, both SAF
and UDCA impeded CD induced tumor invasiveness of MKN-74 by 30-50%. Conclusions:
Our results indicate that signaling of hydrophobic bile acid such as CD in
gastric cancer cells is through PKC activation and COX-2 induction, which leads
to increased cellular invasion. By perturbing the bile acid pool, UDCA attenuates
CD-induced PGE2 synthesis and tumor invasiveness.
PMID- 29942194
TI - Nocturia: Evaluation and Current Management Strategies.
AB - Nocturia is a complex condition that not only significantly affects quality of
life, but may be an indicator of systemic disease. Initial assessment includes a
detailed history and physical examination and completion of a frequency volume
chart to help identify underlying causes, such as sleep disorders, bladder
storage disorders, and polyuria. Treatment with alpha-blockers or antimuscarinic
medications may help if the underlying cause is determined to be benign prostatic
hyperplasia or overactive bladder, respectively. Treatment options for nocturnal
polyuria have been limited to behavioral therapy and off-label use of timed
diuretics and desmopressin. Desmopressin acetate nasal spray (NoctivaTM, Avadel
Pharmaceuticals, Chesterfield, MO) was approved by the US Food and Drug
Administration in 2017 for the treatment of nocturia due to nocturnal polyuria in
adults who awaken at least twice nightly and has shown efficacy in reducing
nocturnal voids by >=50% in up to 49% of patients in clinical trials.
PMID- 29942195
TI - Factors Associated With Postoperative Infection After Percutaneous
Nephrolithotomy.
AB - Numerous studies have investigated risk factors for the development of
postoperative infection in percutaneous nephrolithotomy (PCNL) patients. Herein,
we describe our meta-analysis of the risk factors for the prediction of post-PCNL
infectious complications. We searched electronic databases using a combination of
the terms percutaneous nephrolithotomy, risk factors, infection, and sepsis. The
primary outcome was post-PCNL infection as defined by fever >38 degrees C or
sepsis as defined by the Sepsis Consensus Definition Committee. Risk factors for
infection in each study were identified and included for analysis if present in
at least two studies. We used quantitative effect sizes in odds ratio to assess
each endpoint. After application of criteria, 24 studies were found, of which 12
were prospective and 12 were retrospective. Of the prospective studies,
preoperative urine culture, renal pelvis culture, stone culture, number of access
points, hydronephrosis, perioperative blood transfusion, and struvite stone
composition were found to be significantly associated with postoperative
infection. Of the 12 retrospective studies, preoperative urine culture, stone
cultures, number of access points, blood transfusion, stone size, and staghorn
formation were associated with infection. Preoperative urine culture, stone
culture, number of access points, and need for blood transfusion were
consistently found to be significant factors. This indicates that the presence of
bacteria in the urine/stone preoperatively as well as the amount of trauma the
kidney sustains during the procedure are major predictors of postoperative
infection.
PMID- 29942196
TI - Differentiating Molecular Risk Assessments for Prostate Cancer.
AB - It is critically important to the evolving goals of prostate biopsy to find
clinically significant cancer with lethal potential and avoid detection of
indolent disease. Better tests and markers are required for improved detection of
clinically significant prostate cancer and avoidance of biopsies in men with
indolent disease. Currently, there are myriad alternative prostate cancer risk
assessment tests available derived from serum and urine that are designed to
improve the specificity for detection of "significant" prostate cancer. Herein we
discuss these tests and their clinical implications.
PMID- 29942197
TI - Transrectal Ultrasound-guided Versus Transperineal Mapping Prostate Biopsy:
Complication Comparison.
AB - Herein, the authors compare morbidity in men who underwent both transrectal
ultrasound-guided (TRUS) prostate biopsy and transperineal mapping biopsy (TPMB)
at two institutions with extensive experience in both procedures. We also
identified strategies and predictive factors to reduce morbidity for both
procedures. In our study, 379 men from two institutions, of which 265 (69.9%) had
a prior TRUS-guided biopsy, also had TPMB performed via a template with biopsies
taken at 5-mm intervals. Men in the TRUS group had a median of 12 cores sampled
whereas the TPMB group had 51.5 (range, 16-151). The median biopsy density was
1.1 core/cc prostate volume. Median age and prostate-specific antigen (PSA) level
were 65 years (range, 34-86) and 5.5 ng/mL (range, 0.02-118). Of these men, 11 of
265 (4.2%) who had TRUS biopsy developed urinary tract infection compared with 3
of 379 (0.79%) of those with mapping biopsy. Infection was 14.8% in TRUS biopsy
group with 13 or more cores versus 2.9% in those with 12 or less (OR, 5.8; 95%
CI, 1.6-21.2; P = 0.003). No men developed retention after TRUS biopsy whereas 30
of 379 (7.9%) did following TPMB. Older age, larger prostate volume (PV), and
higher core number were associated with retention. On linear regression only age
(P = 0.010) and PV (P = 0.016) remained as significant associations. Men older
than 65 years had 12.8% versus 3.9% (OR, 3.7; 95% CI, 1.6-8.4, P = 0.001) and PV
greater than 42 cc had 13.4% versus 2.7% (OR, 5.7; 95% CI, 2.1-15.1) retention
incidence. In the present study TPMB is rarely associated with infection (0.78%)
but more commonly with urinary retention (7.9%). Men older than 65 years and with
PV greater than 42 cc were at four to five times greater retention risk.
Consideration should be given to discharging these men with a urinary catheter
following TPMB.
PMID- 29942198
TI - LUGPA Onsite and LUGPA Virtual Crossfire Programs Offer Novel Alternatives to
Attending an Out-oftown LUGPA Meeting.
PMID- 29942199
TI - Best of the 2017 Society for Pediatric Urology Fall Congress.
PMID- 29942200
TI - Bladder Cancer Academy 2018 Selected Summaries.
PMID- 29942201
TI - Management of Recurrent Non-Muscle Invasive Bladder Cancer.
PMID- 29942202
TI - Penile Fracture.
PMID- 29942203
TI - Management of Obstructive Benign Prostatic Hyperplasia With a >200 mL Gland.
PMID- 29942204
TI - Management of Penile Cancer.
PMID- 29942205
TI - A Potential Link: Cross-fused Renal Ectopia With Concomitant Absent Left
Testicle.
AB - Cross-fused renal ectopia (CFRE) is a rare congenital anomaly in which both
kidneys are located on a unilateral side of the retroperitoneal space. The ureter
of the ectopic kidney is seen to pass over the midline to insert in its normal
anatomic position. Frequently this anomaly goes undetected until there is
radiologic screening for other purposes or when other genitourinary issues are
investigated. Although frequently isolated, this condition has been reported to
be associated with other congenital anomalies, genetic disorders, and various
urogenital anomalies more than 50% of the time. However, we found no cases
linking CFRE with a solitary testicle. This is a case of a 30-year-old man with
left-to-right CFRE with concomitant absent left testicle and obstructing distal
calculus.
PMID- 29942206
TI - Craig A. Reickert, MD, FACS, FASCRS.
PMID- 29942207
TI - Diverticular Disease.
PMID- 29942208
TI - Epidemiology and Pathophysiology of Diverticular Disease.
AB - Colonic diverticular disease is a common health care issue which has historically
been attributed to western countries and older age population. Recent studies
have shown a rise in incidence among developing countries that have adopted
western diets as well as rise in prevalence among younger patients. In this
article, the authors discuss the incidence, epidemiology, and pathophysiology of
colonic diverticular disease.
PMID- 29942209
TI - Medical Management of Diverticular Disease.
AB - This article reviews the current literature supporting the non-surgical options
for treatment in acute uncomplicated diverticulitis, complicated diverticulitis,
and options for prevention of recurrent diverticulitis.
PMID- 29942210
TI - Current Status of the Radiologic Assessment of Diverticular Disease.
AB - Radiologic assessment plays a vital role in the management of diverticulitis. It
not only helps in the diagnosis, but also helps to guide the management. As
technology has progressed, different modalities have offered insight into the
treatment of this disease process. Through various trials and studies, certain
modalities stand above the rest in terms of sensitivity and specificity. Computed
tomography (CT) imaging has also proved to help us guide the management through a
grading system. Newer studies show us the advantages of other modalities such as
ultrasound and magnetic resonance imaging (MRI). Though there is much research
yet to be done with these modalities, they do show a lot of potential.
PMID- 29942211
TI - Considerations and Changes in the Evaluation, Management, and Outcomes in the
Management of Diverticular Disease: The Diagnosis, Pathology, and Treatment of
Diverticular Colitis.
AB - Diverticular colitis, also known as segmental colitis associated with
diverticulosis, is a colonic inflammatory disorder on the spectrum of
inflammatory bowel disease (IBD). The disease consists of macroscopic and
microscopic inflammation affecting inter-diverticular mucosa, sparing peri
diverticular mucosa, with inflammation confined to the descending and sigmoid
colon. The disease likely arises from the altered immune response of an
individual, genetically susceptible to the IBD spectrum of diseases. Patients
with segmental colitis associated with diverticulosis (SCAD) are typically older,
and likely represent a subgroup of IBD-susceptible patients who lacked an
environmental trigger until that point in their life. Most patients remain in
remission with initial treatments of mesalamine or topical steroids, and
maintenance mesalamine afterwards. Only the most severe form of the disease
necessitates immunomodulatory therapy and the consideration of surgery.
PMID- 29942212
TI - Management of Diverticular Disease in the Setting of Other Colorectal Pathology:
Data on Simultaneous Issues in Segmental Colitis, Inflammatory Bowel Disease,
Cancer, and Complications.
AB - Diverticulosis of the colon is a very common anatomical condition. In the Western
world, it affects more than 70% of over 65 years old population and represents
the fifth most important gastrointestinal disease in terms of health care costs
in Western countries. The diagnosis of diverticular disease and diverticulitis
can be challenging. Often, there is overlap with other colonic pathologies, such
as segmental colitis, ischemia, inflammatory bowel disease, cancer, or infectious
colitis. Management of diverticular disease in these settings might be different.
PMID- 29942213
TI - Current Options for the Emergency Management of Diverticular Disease and Options
to Reduce the Need for Colostomy.
AB - This article reviews the current options and recommendations for the emergency
management of acute diverticulitis, including the spectrum of antibiotics,
percutaneous drainage, laparoscopic lavage, and surgical options for resection
with the restoration of bowel continuity.
PMID- 29942215
TI - Management of Diverticular Bleeding: Evaluation, Stabilization, Intervention, and
Recurrence of Bleeding and Indications for Resection after Control of Bleeding.
AB - Diverticular bleeding is the most common cause of lower gastrointestinal bleeding
with nearly 200,000 admissions in the United States annually. Less than 5% of
patients with diverticulosis present with diverticular bleeding and present
usually as painless, intermittent, and large volume of lower gastrointestinal
bleeding. Management algorithm for patients presenting with diverticular bleeding
includes resuscitation followed by diagnostic evaluation. Colonoscopy is the
recommended first-line investigation and helps in identifying the stigmata of
recent hemorrhage and endoscopic management of the bleeding. Radionuclide
scanning is the most sensitive but least accurate test due to low spatial
resolution. Angiography is helpful when patients are actively bleeding and
therapeutic interventions are performed with angioembolization. Surgery for
diverticular bleeding is necessary when associated with hemodynamic instability
and after failed endoscopic or angiographic interventions. When the bleeding site
is localized preoperatively, partial colectomy is sufficient, but subtotal
colectomy is necessary when localization is not possible preoperatively.
PMID- 29942216
TI - Evaluation of Quality of Life and Surgical Outcomes for Treatment of Diverticular
Disease.
AB - The prevalence of diverticular disease in the Western and industrialized nations
has increased over the last century, and our understanding of this disease and
its management continues to evolve. In this article, we review the literature
regarding the postoperative quality of life (QOL) and functional outcomes
following surgical management of diverticulitis, including information regarding
bowel function, recurrence of symptoms, and other postoperative sequelae. While
objective parameters, such as attacks of diverticulitis, complications, and
clinical episodes have been studied, there is a paucity of data on less objective
factors, such as overall patient satisfaction after operative management of
diverticular disease. The literature shows improvement in QOL following surgical
intervention for diverticulitis if preoperative QOL was significantly low,
secondary to severe/complicated diverticulitis. However, a subset of patients
does continue to have symptoms following surgical intervention for
diverticulitis. Often neglected in the literature, there remains a need for
prospective data evaluating preoperative function to ascertain the impact of
surgery on patients' QOL and postoperative function.
PMID- 29942214
TI - Surgical Management of Diverticular Disease in the Elective Setting.
AB - Diverticulosis is a common condition that has increased in prevalence in
industrialized countries over the past century. Estimates of developing
diverticular disease in the United states range from 5% by 40 years of age up, to
over 80% by age 80. It is estimated that approximately 20% of patients with
diverticulosis develop diverticulitis over the course of their lifetime.
Diverticular disease can be divided into simple and chronic diverticulitis with
various sub categories. There are various instances and circumstances where
elective resection is indicated for both complex and simple forms of this disease
process. When planning surgery there are general preoperative considerations that
are important to be reviewed prior to surgery. There are also more specific
considerations depending on secondary problem attributed to diverticulitis, that
is, fistula vs stricture. Today, treatment for elective resection includes open,
laparoscopic and robotic surgery. Over the last several years we have moved away
from open surgery to laparoscopic surgery for elective resection. With the advent
of robotic surgery and introduction of 3D laparoscopic surgery the discussion of
superiority, equivalence between these modalities, is and should remain an
important discussion topic.
PMID- 29942218
TI - Third-Space Endoscopy.
PMID- 29942217
TI - Uncommon Diverticular Disease.
AB - This article describes the epidemiology, pathogenesis, diagnosis, and treatment
of three rare variants of diverticular disease: cecal and right-sided colonic
diverticula, giant colonic diverticula, and small bowel diverticula.
PMID- 29942219
TI - GASTRO-HEP News.
PMID- 29942220
TI - Recent Advances in Third-Space Endoscopy.
AB - The capabilities of interventional gastrointestinal endoscopy have significantly
increased over the past several decades. Improvements in devices and techniques
have eased the transfer of novel concepts from bench to bedside. The concept of
submucosal endoscopy with mucosal flap safety valve has enabled endoscopists to
securely use submucosal space, or third space. Peroral endoscopic myotomy was the
initial procedure performed utilizing submucosal space in patients with
achalasia. Subsequently, this technique has been used successfully for removal of
subepithelial tumors from the esophagus and the stomach. All third-space
endoscopy procedures use a similar technique-a submucosal tunnel is created, and
then a myotomy is performed or a subepithelial tumor is dissected away from the
initial site of the mucosal incision. The other potential indications for third
space endoscopy include refractory gastroparesis, Zenker diverticulum, and
restoration of completely obstructed esophageal lumen. Although the emerging data
look promising for peroral endoscopic myotomy and pyloromyotomy, randomized
studies with long-term follow-up are lacking. Submucosal endoscopy is largely
safe, and the occurrence of major adverse events is uncommon. Therefore, the
majority of third-space endoscopy procedures can be performed in an endoscopy
suite. The most frequently encountered adverse events during submucosal endoscopy
include those related to insufflation, bleeding, and perforations.
PMID- 29942222
TI - Elimination of Hepatitis B and C Virus Infections.
PMID- 29942221
TI - Evaluation of Dysplasia in Barrett Esophagus.
AB - Barrett esophagus (BE) is the precursor lesion to adenocarcinoma of the
esophagus. The current surveillance strategy of 4-quadrant Seattle protocol
biopsies has been associated with sampling error and missing higher-risk lesions,
and there is often less adherence to endoscopic surveillance with long segments.
Advancements in endoscopic imaging and sampling techniques allow for better
surveillance of BE, particularly when assessing for dysplasia. This article
highlights the key endoscopic imaging and sampling advancements in the evaluation
of dysplasia in BE.
PMID- 29942223
TI - Safety and Positioning of Vedolizumab in Patients With Inflammatory Bowel
Disease.
PMID- 29942224
TI - Risk of Hepatocellular Carcinoma in Patients With Nonalcoholic Steatohepatitis.
PMID- 29942225
TI - The Emerging Role of Mast Cells in Irritable Bowel Syndrome.
PMID- 29942226
TI - Optical Coherence Tomography for Barrett Esophagus.
PMID- 29942227
TI - New Trends in Diagnosis, Monitoring and Management of Tumour Diseases.
PMID- 29942228
TI - Basic Concepts of Cancer: Genomic Determination.
PMID- 29942229
TI - Interaction Between Cell Death and Cell Proliferation in Cancer.
PMID- 29942230
TI - Global Approach to Biomedicine: Functional Genomics and Proteomics.
PMID- 29942231
TI - Biology of Metastasis With Focus on Proteases.
PMID- 29942232
TI - The Potential of Cancer Screening Programmes in Europe.
PMID- 29942233
TI - Cancer and Environment.
PMID- 29942235
TI - Laboratory Diagnosis and Monitoring of Leukaemias and Lymphomas at Molecular
Level.
PMID- 29942234
TI - Tumour Markers: Rationale Use.
PMID- 29942236
TI - Breast Cancer and Her-2/Neu.
PMID- 29942237
TI - Psa and Other Biomarkers for Early Detection, Diagnosis and Monitoring of Prost a
Te Cancer.
PMID- 29942238
TI - Colorectal Carcinoma.
PMID- 29942239
TI - Pharmacogenetic And Tumour Drugs.
PMID- 29942240
TI - Towards Automation for Molecular Diagnosis of Cancer.
PMID- 29942241
TI - Ethics and Quality Assessment in Genetic Testing.
PMID- 29942242
TI - Proteomics: A Study of Therapy Resistance in Cancer Cells.
PMID- 29942243
TI - Detection of Disseminated Cancer Cells in Blood.
PMID- 29942244
TI - Gene Expression Profiles - What the Clinician Needs to Know.
PMID- 29942245
TI - The associations between diet and physical activity with body composition and
walking a timed distance in adults with Prader-Willi syndrome.
AB - Background: Research on aging in Prader-Willi syndrome (PWS) is limited, although
people with PWS are living longer. Individuals with PWS present with high fat
mass, low lean mass, and low levels of physical activity (PA). Previous reports
in children and young adults with PWS show inadequate nutrient intake and body
fat percentage indicating obesity. Previous studies in PWS rarely included
individuals beyond young adulthood, especially studies conducted in the United
States. This study includes adults from 18 to 62 years of age, and includes 19 of
the estimated 60 adult individuals with PWS in Oklahoma. Because individuals with
PWS are living longer, information must be provided on aging with PWS. This study
is a report of the initial data for a planned longitudinal study on aging with
PWS. Objective: Determine associations between body composition, diet, PA, and a
timed walk for adults with PWS, and to assess adequacy of dietary intake for
those individuals aging with PWS. Design: This cross-sectional investigation
determined dietary habits, PA, and body composition of adults with PWS, and
tested associations between these variables. Results: Participants ranged in age
from 18 to 62 years. They had healthier body composition, at 26.8% body fat, than
previously reported. Mean body mass index (BMI) was in the overweight range at
26.7. Those who consumed higher amounts of fat (as a percent of total
kilocalories) had statistically significant lower body fat percentage, but this
may simply reflect that individuals with lower body fat percentages felt freer to
consume fat. Mean steps taken per day was 7631.7 steps but only 16% of
participants met healthy PA recommendations despite participating in daily
structured exercise. All participants' diets met Dietary Guidelines for
macronutrient distribution, but 80% were deficient in calcium, 100% were
deficient in dietary vitamin D, and 87% were deficient in fiber. Sample size was
small, so it was difficult to reach statistical significance, despite seeing
clinical significance. Conclusions: Recommend working toward healthy PA
recommendations for all age groups by decreasing time in sedentary activity.
Recommend increasing vitamin A and D fortified dairy products and high-fiber
foods, and consider dietary supplementation, especially for calcium, vitamin D,
and fiber.
PMID- 29942246
TI - Is boiled food spice curcumin still biologically active? An experimental
exploration.
AB - Background: As the major active component of turmeric (Curcuma longa), curcumin
is widely used as a spice and food coloring agent, and also possesses multiple
biological activities and therapeutic potential for neurodegenerative diseases.
To answer the paradox between curcumin's biological activities and poor systemic
bioavailability, we proposed that degradation products of curcumin may make
important contributions to its biological activities, which needs to be verified.
In addition, curcumin is usually heated or boiled used as a spice, it is
necessary to explore whether boiled curcumin, which degrades readily, is still
biologically active. Methods: Thus, in the present study we investigated the
protective effects of curcumin and boiled curcumin mixture on H2O2-induced
oxidative damage in PC12 cells, a widely used model for neurons. Results: Results
showed that in spite of high degradation rates, boiled curcumin mixture still
possessed similar protective activities like parent curcumin, and could
effectively rescue PC12 cells against H2O2-induced damage, via decreasing
production of reactive oxygen species and malondialdehyde, reducing caspase-3 and
caspase-9 activities. Moreover, curcumin's degradation products including ferulic
acid, vanillin and vanillic acid could also improve PC12 cells survival rate.
Conclusion: Our findings indicated that boiled curcumin mixtures still possessed
protective activity for PC12 cells, and supported the contribution of degradation
products to biological activities of curcumin.
PMID- 29942247
TI - Biological and Cognitive Frameworks for a Mental Timeline.
PMID- 29942249
TI - Activity-Dependent Pre-miR-134 Dendritic Localization Is Required for Hippocampal
Neuron Dendritogenesis.
AB - microRNAs (miRNAs) have emerged as critical regulators of neuronal dendrite
development. Specific precursor (pre-)miRNAs are actively transported to
dendrites, but whether this process is regulated by neuronal activity and
involved in activity-dependent dendritogenesis is unknown. Here we show that
BDNF, a neurotrophin that is released in response to increased neuronal activity,
promotes dendritic accumulation of pre-miR-134. Dendritic accumulation, but not
transcription of pre-miR-134, is abrogated by treatment of neurons with the NMDA
receptor (NMDAR) antagonist APV. Furthermore, APV interferes with BDNF-mediated
repression of the known miR-134 target Pumilio 2 (Pum2) in a miR-134 binding site
specific manner. At the functional level, both APV treatment and knockdown of the
pre-miR-134 transport protein DHX36 antagonize BDNF-induced dendritogenesis.
These effects are likely mediated by reduced dendritic miR-134 activity, since
both transfection of a synthetic miR-134 duplex or of a dendritically targeted
pre-miR-134-181a chimera rescues BDNF-dependent dendritogenesis in the presence
of APV. In conclusion, we have identified a novel NMDAR-dependent mechanism
involved in the activity-dependent control of miRNA function during neuronal
development.
PMID- 29942248
TI - Visual Neurons in the Superior Colliculus Discriminate Many Objects by Their
Historical Values.
AB - The superior colliculus (SC) is an important structure in the mammalian brain
that orients the animal toward distinct visual events. Visually responsive
neurons in SC are modulated by visual object features, including size, motion,
and color. However, it remains unclear whether SC activity is modulated by non
visual object features, such as the reward value associated with the object. To
address this question, three monkeys were trained (>10 days) to saccade to
multiple fractal objects, half of which were consistently associated with large
rewards while other half were associated with small rewards. This created
historically high-valued ('good') and low-valued ('bad') objects. During the
neuronal recordings from the SC, the monkeys maintained fixation at the center
while the objects were flashed in the receptive field of the neuron without any
reward. We found that approximately half of the visual neurons responded more
strongly to the good than bad objects. In some neurons, this value-coding
remained intact for a long time (>1 year) after the last object-reward
association learning. Notably, the neuronal discrimination of reward values
started about 100 ms after the appearance of visual objects and lasted for more
than 100 ms. These results provide evidence that SC neurons can discriminate
objects by their historical (long-term) values. This object value information may
be provided by the basal ganglia, especially the circuit originating from the
tail of the caudate nucleus. The information may be used by the neural circuits
inside SC for motor (saccade) output or may be sent to the circuits outside SC
for future behavior.
PMID- 29942251
TI - Analysis of Gene Expression Variance in Schizophrenia Using Structural Equation
Modeling.
AB - Schizophrenia (SCZ) is a psychiatric disorder of unknown etiology. There is
evidence suggesting that aberrations in neurodevelopment are a significant
attribute of schizophrenia pathogenesis and progression. To identify biologically
relevant molecular abnormalities affecting neurodevelopment in SCZ we used
cultured neural progenitor cells derived from olfactory neuroepithelium (CNON
cells). Here, we tested the hypothesis that variance in gene expression differs
between individuals from SCZ and control groups. In CNON cells, variance in gene
expression was significantly higher in SCZ samples in comparison with control
samples. Variance in gene expression was enriched in five molecular pathways:
serine biosynthesis, PI3K-Akt, MAPK, neurotrophin and focal adhesion. More than
14% of variance in disease status was explained within the logistic regression
model (C-value = 0.70) by predictors accounting for gene expression in 69 genes
from these five pathways. Structural equation modeling (SEM) was applied to
explore how the structure of these five pathways was altered between SCZ patients
and controls. Four out of five pathways showed differences in the estimated
relationships among genes: between KRAS and NF1, and KRAS and SOS1 in the MAPK
pathway; between PSPH and SHMT2 in serine biosynthesis; between AKT3 and TSC2 in
the PI3K-Akt signaling pathway; and between CRK and RAPGEF1 in the focal adhesion
pathway. Our analysis provides evidence that variance in gene expression is an
important characteristic of SCZ, and SEM is a promising method for uncovering
altered relationships between specific genes thus suggesting affected gene
regulation associated with the disease. We identified altered gene-gene
interactions in pathways enriched for genes with increased variance in expression
in SCZ. These pathways and loci were previously implicated in SCZ, providing
further support for the hypothesis that gene expression variance plays important
role in the etiology of SCZ.
PMID- 29942252
TI - Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5'UTR and PI3K
Signaling.
AB - The alpha-secretase "a disintegrin and metalloproteinase domain-containing
protein" (ADAM10) is involved in the processing of amyloid precursor protein
(APP). Upregulation of ADAM10 precludes the generation of neurotoxic beta-amyloid
protein (Abeta) and represents a plausible therapeutic strategy for Alzheimer's
disease (AD). In this study, we explored compounds that can potentially promote
the expression of ADAM10. Therefore, we performed high-throughput small-molecule
screening in SH-SY5Y (human neuroblastoma) cells that stably express a luciferase
reporter gene driven by the ADAM10 promoter, including a portion of its 5'
untranslated region (5'UTR). This has led to the discovery of cosmosiin (apigenin
7-O-beta-glucoside). Here, we report that in human cell lines (SH-SY5Y and
HEK293), cosmosiin proportionally increased the levels of the immature and mature
forms of the ADAM10 protein without altering its mRNA level. This effect was
attenuated by translation inhibitors or by deleting the 5'UTR of ADAM10,
suggesting that a translational mechanism was responsible for the increased
levels of ADAM10. Luciferase deletion assays revealed that the first 144
nucleotides of the 5'UTR were necessary for mediating the cosmosiin-induced
enhancement of ADAM10 expression in SH-SY5Y cells. Cosmosiin failed to increase
the levels of the ADAM10 protein in murine cells, which lack native expression of
the ADAM10 transcript containing the identified 5'UTR element. The potential
signaling pathway may involve phosphatidylinositide 3-kinase (PI3K) because
pharmacological inhibition of PI3K attenuated the effect of cosmosiin on the
expression of the ADAM10 protein. Finally, cosmosiin attenuated Abeta generation
because the levels of Abeta40/42 in HEK-APP cells were significantly reduced
after cosmosiin treatment. Collectively, we found that the first 144 nucleotides
of the ADAM10 5'UTR, and PI3K signaling, are involved in cosmosiin-induced
enhancement of the expression of ADAM10 protein. These results suggest that
cosmosiin may be a potential therapeutic agent in the treatment of AD.
PMID- 29942250
TI - Stable STIM1 Knockdown in Self-Renewing Human Neural Precursors Promotes
Premature Neural Differentiation.
AB - Ca2+ signaling plays a significant role in the development of the vertebrate
nervous system where it regulates neurite growth as well as synapse and
neurotransmitter specification. Elucidating the role of Ca2+ signaling in
mammalian neuronal development has been largely restricted to either small animal
models or primary cultures. Here we derived human neural precursor cells (NPCs)
from human embryonic stem cells to understand the functional significance of a
less understood arm of calcium signaling, Store-operated Ca2+ entry or SOCE, in
neuronal development. Human NPCs exhibited robust SOCE, which was significantly
attenuated by expression of a stable shRNA-miR targeted toward the SOCE molecule,
STIM1. Along with the plasma membrane channel Orai, STIM is an essential
component of SOCE in many cell types, where it regulates gene expression.
Therefore, we measured global gene expression in human NPCs with and without
STIM1 knockdown. Interestingly, pathways down-regulated through STIM1 knockdown
were related to cell proliferation and DNA replication processes, whereas post
synaptic signaling was identified as an up-regulated process. To understand the
functional significance of these gene expression changes we measured the self
renewal capacity of NPCs with STIM1 knockdown. The STIM1 knockdown NPCs
demonstrated significantly reduced neurosphere size and number as well as
precocious spontaneous differentiation toward the neuronal lineage, as compared
to control cells. These findings demonstrate that STIM1 mediated SOCE in human
NPCs regulates gene expression changes, that in vivo are likely to
physiologically modulate the self-renewal and differentiation of NPCs.
PMID- 29942255
TI - Effects of a 7-Day Meditation Retreat on the Brain Function of Meditators and Non
Meditators During an Attention Task.
AB - Meditation as a cognitive enhancement technique is of growing interest in the
field of health and research on brain function. The Stroop Word-Color Task (SWCT)
has been adapted for neuroimaging studies as an interesting paradigm for the
understanding of cognitive control mechanisms. Performance in the SWCT requires
both attention and impulse control, which is trained in meditation practices. We
presented SWCT inside the MRI equipment to measure the performance of meditators
compared with non-meditators before and after a meditation retreat. The aim of
this study was to evaluate the effects of a 7-day Zen intensive meditation
training (a retreat) on meditators and non-meditators in this task on performance
level and neural mechanisms. Nineteen meditators and 14 non-meditators were
scanned before and after a 7-day Zen meditation retreat. No significant
differences were found between meditators and non-meditators in the number of the
correct responses and response time (RT) during SWCT before and after the
retreat. Probably, due to meditators training in attention, their brain activity
in the contrast incongruent > neutral during the SWCT in the anterior cingulate,
ventromedial prefrontal cortex/anterior cingulate,
caudate/putamen/pallidum/temporal lobe (center), insula/putamen/temporal lobe
(right) and posterior cingulate before the retreat, were reduced compared with
non-meditators. After the meditation retreat, non-meditators had reduced
activation in these regions, becoming similar to meditators before the retreat.
This result could be interpreted as an increase in the brain efficiency of non
meditators (less brain activation in attention-related regions and same
behavioral response) promoted by their intensive training in meditation in only 7
days. On the other hand, meditators showed an increase in brain activation in
these regions after the same training. Intensive meditation training (retreat)
presented distinct effects on the attention-related regions in meditators and non
meditators probably due to differences in expertise, attention processing as well
as neuroplasticity.
PMID- 29942253
TI - Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic
Inactivity.
AB - The morphology and function of neuronal synapses are regulated by neural
activity, as manifested in activity-dependent synapse maturation and various
forms of synaptic plasticity. Here we employed cryo-electron tomography (cryo-ET)
to visualize synaptic ultrastructure in cultured hippocampal neurons and
investigated changes in subcellular features in response to chronic inactivity, a
paradigm often used for the induction of homeostatic synaptic plasticity. We
observed a more than 2-fold increase in the mean number of dense core vesicles
(DCVs) in the presynaptic compartment of excitatory synapses and an almost 20
fold increase in the number of DCVs in the presynaptic compartment of inhibitory
synapses after 2 days treatment with the voltage-gated sodium channel blocker
tetrodotoxin (TTX). Short-term treatment with TTX and the N-methyl-D-aspartate
receptor (NMDAR) antagonist amino-5-phosphonovaleric acid (AP5) caused a 3-fold
increase in the number of DCVs within 100 nm of the active zone area in
excitatory synapses but had no significant effects on the overall number of DCVs.
In contrast, there were very few DCVs in the postsynaptic compartments of both
synapse types under all conditions. These results are consistent with a role for
presynaptic DCVs in activity-dependent synapse maturation. We speculate that
these accumulated DCVs can be released upon reactivation and may contribute to
homeostatic metaplasticity.
PMID- 29942254
TI - Coherence of the Surface EMG and Common Synaptic Input to Motor Neurons.
AB - Coherence between electromyographic (EMG) signals is often used to infer the
common synaptic input to populations of motor neurons. This analysis, however,
may be limited due to the filtering effect of the motor unit action potential
waveforms. This study investigated the ability of surface EMG-EMG coherence to
predict common synaptic input to motor neurons. Surface and intramuscular EMG
were recorded from two locations of the tibialis anterior muscle during steady
ankle dorsiflexions at 5 and 10% of the maximal force in 10 healthy individuals.
The intramuscular EMG signals were decomposed to identify single motor unit spike
trains. For each trial, the strength of the common input in different frequency
bands was estimated from the coherence between two cumulative spike trains,
generated from sets of single motor unit spike trains (reference measure). These
coherence values were compared with those obtained from the coherence between the
surface EMG signals (raw, rectified, and high-passed filtered at 250 Hz before
rectification) using linear regression. Overall, the high-pass filtering of the
EMG prior to rectification did not substantially change the results with respect
to rectification only. For both signals, the correlation of EMG coherence with
motor unit coherence was strong at 5% MVC (r2 > 0.8; p < 0.01), but only for
frequencies > 5 Hz. At 10% MVC, the correlation between EMG and motor unit
coherence was only significant for frequencies > 15 Hz (r2 > 0.8; p < 0.01).
However, when using raw EMG for coherence analysis, the only significant relation
with motor unit coherence was observed for the bandwidth 5-15 Hz (r2 > 0.68; p =
0.04). In all cases, there was no association between motor unit and EMG
coherence for frequencies < 5 Hz (r2 <= 0.2; p >= 0.51). In addition, a
substantial error in the best linear fit between motor unit and EMG coherence was
always present. In conclusion, high-frequency (>5 Hz) common synaptic inputs to
motor neurons can partly be estimated from the rectified surface EMG at low-level
steady contractions. The results, however, suggest that this association is
weakened with increasing contraction intensity and that input at lower
frequencies during steady isometric contractions cannot be detected accurately by
surface EMG coherence.
PMID- 29942256
TI - Comparison of Administration Routes on the Protective Effects of Bee Venom
Phospholipase A2 in a Mouse Model of Parkinson's Disease.
AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder
worldwide. Progressive loss of dopaminergic neurons in the substantia nigra (SN)
and their synaptic terminal connections in the striatum are main
characterizations of PD. Although many efforts have been made to develop
therapeutics, no treatment has been proven effective. We previously demonstrated
that bvPLA2 can protect dopaminergic neurons by modulating neuroinflammatory
responses in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse
model of PD. The cellular basis for the neuroprotective response of bvPLA2 was
the induction of CD4+CD25+ regulatory T cells (Tregs), a population known to
suppress immune activation and maintain homeostasis and tolerance to self
antigen. The aim of the present study was to investigate the effects of different
routes of bvPLA2 administration in a PD mouse model. Neurobehavioral assessment
revealed progressive deterioration in locomotor functions of the MPTP group
compared with the control group. However, such functions were improved following
subcutaneous (s.c.) bvPLA2 administration. The results showed that the s.c. route
of bvPLA2 administration contributed to the induction of Treg cells and the
reduction of Th1 and Th17 populations, demonstrating that the neuroprotective
effects were associated with reduced tyrosine hydroxylase (TH)-positive
dopaminergic neurons and microglia. These results suggested that the s.c. bvPLA2
injection could be beneficial for treating aspects of PD.
PMID- 29942257
TI - Pharmacokinetics of Human Red Blood Cell Microparticles Prepared Using High
Pressure Extrusion Method.
AB - Red blood cell microparticles (RMPs) is a high potency hemostatic agent, which
may serve as a viable therapeutic approach. They generate thrombin in vitro and
effective in arresting bleeding in animal bleeding models. However, prior to
ascertaining the clinical efficacy of RMPs, detailed preclinical evaluation is
necessary. Therefore, we aimed to characterize RMPs, ascertain their stability,
and determine their pharmacokinetics in rats. RMPs were prepared from human RBCs
by a high-pressure extrusion method. Pharmacokinetic parameters were computed
from groups receiving various RMPs dosing regimens. Volume of distribution,
elimination rate constant, and clearance for RMPs were also assessed. Major
portion of prepared microparticles were RMPs and a very small portion of
particles were from platelets and leukocytes. RMPs were stable when stored at 5
and -20 degrees C for at least 12 months. In vivo half-life was found to vary for
each paradigm, but in general, was less than 2 min for most of the paradigms
evaluated. Our results demonstrate that RMPs are stable during prolonged storage
and have a short half-life. Therefore, the clinical use of RMPs as a hemostatic
agent, within a tailored treatment paradigm, may be advantageous in achieving
prolonged systemic therapeutic benefit without provoking any thrombotic
complications.
PMID- 29942258
TI - Trichostatin a Protects Dendritic Cells Against Oxygen-Glucose Deprivation via
the SRSF3/PKM2/Glycolytic Pathway.
AB - Dendritic cells (DCs) are important to the immune system and are frequently
recruited to hypoxic regions, especially during acute myocardial infarction
(AMI). Emerging data indicate that histone deacetylase (HDAC) inhibitors possess
immunomodulatory functions. We previously showed in a rat model of AMI that the
HDAC inhibitor TSA improved tissue repair, and this was accompanied by increased
DC infiltration in the infarct region, suggesting an important role of TSA in
modulating DC functions. To study the potential modulatory effect of TSA on DCs,
we exploited an in vitro model of hypoxia and glucose deprivation. Culturing of
DCs in the presence of 200 nM TSA improved DC survival under hypoxia and glucose
deprivation. However, on a phenotypic level, TSA induced the expression of the DC
co-stimulatory molecules CD80 and CD86, decreased FITC-dextran uptake, and
facilitated DC migration. Moreover, TSA altered cytokine secretion by reducing
the pro-inflammatory cytokines IL-1beta, IL-10, IL-12, and TGF-beta. Furthermore,
TSA treatment enhanced HIF-1alpha-dependent glycolytic gene expression and
increased pyruvate kinase M2 by upregulating SRSF3. These results suggest that by
TSA alters important DC functions under hypoxia and glucose deprivation, and that
TSA is critical for DC function by modulating SRSF3-PKM2-dependent glycolytic
pathways.
PMID- 29942259
TI - Extending in Silico Protein Target Prediction Models to Include Functional
Effects.
AB - In silico protein target deconvolution is frequently used for mechanism-of-action
investigations; however existing protocols usually do not predict compound
functional effects, such as activation or inhibition, upon binding to their
protein counterparts. This study is hence concerned with including functional
effects in target prediction. To this end, we assimilated a bioactivity training
set for 332 targets, comprising 817,239 active data points with unknown
functional effect (binding data) and 20,761,260 inactive compounds, along with
226,045 activating and 1,032,439 inhibiting data points from functional screens.
Chemical space analysis of the data first showed some separation between compound
sets (binding and inhibiting compounds were more similar to each other than both
binding and activating or activating and inhibiting compounds), providing a
rationale for implementing functional prediction models. We employed three
different architectures to predict functional response, ranging from simplistic
random forest models ('Arch1') to cascaded models which use separate binding and
functional effect classification steps ('Arch2' and 'Arch3'), differing in the
way training sets were generated. Fivefold stratified cross-validation outlined
cascading predictions provides superior precision and recall based on an internal
test set. We next prospectively validated the architectures using a temporal set
of 153,467 of in-house data points (after a 4-month interim from initial data
extraction). Results outlined Arch3 performed with the highest target class
averaged precision and recall scores of 71% and 53%, which we attribute to the
use of inactive background sets. Distance-based applicability domain (AD)
analysis outlined that Arch3 provides superior extrapolation into novel areas of
chemical space, and thus based on the results presented here, propose as the most
suitable architecture for the functional effect prediction of small molecules. We
finally conclude including functional effects could provide vital insight in
future studies, to annotate cases of unanticipated functional changeover, as
outlined by our CHRM1 case study.
PMID- 29942260
TI - Impact of Biologic Treatment of Crohn's Disease on the Rate of Surgeries and
Other Healthcare Resources: An Analysis of a Nationwide Database From Poland.
AB - Background: There is conflicting evidence on the impact of biologic treatment on
the rate of complications and surgeries in Crohn's disease (CD). We aimed to
assess real-world consequences of biologic treatment of CD. Methods: All adult
patients with CD treated with infliximab and adalimumab in the years 2012-2014
were identified from the database of the National Health Fund in Poland. Mixed
models were used to assess the impact of biologics on medical resource
utilization by comparing the periods before and after the first use of biologics
(pre-index vs. post-index). The additional analyses including quintile of total
exposure to biologic treatment were performed. Results: Data on 1393 patients
(age, 31.9 years; males, 52.6%) were analyzed over a median of 1064 days (range:
71, 1148). During the post-index period, patients received from one to four
treatments with biologic agents (maximum allowed period of 12 months per
treatment). We observed a reduction in the rates of surgeries (by 27%, p =
0.001), hospitalizations for CD excluding surgical procedures (by 45%, p <
0.001), as well as consumption of antibiotics (by 31%, p < 0.001) and steroids
(by 35%, p < 0.001) in the post-index compared with the pre-index period. The
reduction in the rate of surgeries, hospitalizations for CD, and steroid intake
increased with the increase of exposure to biologic agents. Conclusion: Biologic
treatment changed the management patterns by lowering the rate of surgeries and
other healthcare resources related to complications or worsening of CD. The
reduction in the resource utilization was dependent on the level of exposure to
treatment, suggesting that limitation of the treatment period itself may be
inadequate.
PMID- 29942261
TI - Transient Increase in Cortical Excitability Following Static Stretching of
Plantar Flexor Muscles.
AB - Spinal excitability in humans is inhibited by both passively holding a static
position with the muscle lengthened (static stretching) and by a single non
active lengthening movement. However, whilst immediately after a passive
lengthening movement the inhibition persists for several seconds, there seem to
be an immediate recovery following static stretching. This result is counter
intuitive and could be attributed to methodological procedures. Indeed,
differently to what has been done until now, in order to study whether static
stretching has a transient effect on the neuromuscular pathway, the procedure
should be repeated many times and measurements collected at different time points
after stretching. In the present study we repeated 60 times 30 s static
stretching of ankle plantar flexors and measured tap reflex (T-reflex), Hoffman
reflex (H-reflex), and motor evoked potentials (MEPs) from the Soleus muscle at
several time points, starting from immediately after until 30 s following the
procedure. T-reflex was strongly inhibited (range 31-91%, p = 0.005) and the
inhibition persisted for 30 s showing a slow recovery (r = 0.541, p = 0.037). H
reflex was not affected by the procedure. Stretching increased the size of the
MEPs (p < 0.0001), differences at times 0 and 2 s after stretching (p = 0.015 and
p = 0.047, respectively). These results confirm that static stretching reduces
muscle spindle sensitivity. Moreover it is suggested that post-activation
depression of Ia afferents, which is commonly considered the cause of H-reflex
depression during both dorsiflexion and static stretching, vanished immediately
following stretching or is counteracted by an increased corticospinal
excitability.
PMID- 29942262
TI - Elevated Nicotinamide Phosphoribosyl Transferase in Skeletal Muscle Augments
Exercise Performance and Mitochondrial Respiratory Capacity Following Exercise
Training.
AB - Mice overexpressing NAMPT in skeletal muscle (NamptTg mice) develop higher
exercise endurance and maximal aerobic capacity (VO2max) following voluntary
exercise training compared to wild-type (WT) mice. Here, we aimed to investigate
the mechanisms underlying by determining skeletal muscle mitochondrial
respiratory capacity in NamptTg and WT mice. Body weight and body composition,
tissue weight (gastrocnemius, quadriceps, soleus, heart, liver, and epididymal
white adipose tissue), skeletal muscle and liver glycogen content, VO2max,
skeletal muscle mitochondrial respiratory capacity (measured by high-resolution
respirometry), skeletal muscle gene expression (measured by microarray and qPCR),
and skeletal muscle protein content (measured by Western blot) were determined
following 6 weeks of voluntary exercise training (access to running wheel) in 13
week-old male NamptTg (exercised NamptTg) mice and WT (exercised WT) mice. Daily
running distance and running time during the voluntary exercise training protocol
were recorded. Daily running distance (p = 0.51) and running time (p = 0.85) were
not significantly different between exercised NamptTg mice and exercised WT mice.
VO2max was higher in exercised NamptTg mice compared to exercised WT mice (p =
0.02). Body weight (p = 0.92), fat mass (p = 0.49), lean mass (p = 0.91), tissue
weight (all p > 0.05), and skeletal muscle (p = 0.72) and liver (p = 0.94)
glycogen content were not significantly different between exercised NamptTg mice
and exercised WT mice. Complex I oxidative phosphorylation (OXPHOS) respiratory
capacity supported by fatty acid substrates (p < 0.01), maximal (complex I+II)
OXPHOS respiratory capacity supported by glycolytic (p = 0.02) and fatty acid (p
< 0.01) substrates, and maximal uncoupled respiratory capacity supported by fatty
acid substrates (p < 0.01) was higher in exercised NamptTg mice compared to
exercised WT mice. Transcriptomic analyses revealed differential expression for
genes involved in oxidative metabolism in exercised NamptTg mice compared to
exercised WT mice, specifically, enrichment for the gene set related to the SIRT3
mediated signaling pathway. SIRT3 protein content correlated with NAMPT protein
content (r = 0.61, p = 0.04). In conclusion, NamptTg mice develop higher exercise
capacity following voluntary exercise training compared to WT mice, which is
paralleled by higher mitochondrial respiratory capacity in skeletal muscle. The
changes in SIRT3 targets suggest that these effects are due to remodeling of
mitochondrial function.
PMID- 29942263
TI - Estimation of Complexity of Sampled Biomedical Continuous Time Signals Using
Approximate Entropy.
AB - Non-linear analysis found many applications in biomedicine. Approximate entropy
(ApEn) is a popular index of complexity often applied to biomedical data, as it
provides quite stable indications when processing short and noisy epochs.
However, ApEn strongly depends on parameters, which were chosen in the literature
in wide ranges. This paper points out that ApEn depends on sampling rate of
continuous time signals, embedding dimension, tolerance (under which a match is
identified), epoch duration and low frequency trends. Moreover, contradicting
results can be obtained changing parameters. This was found both in simulations
and in experimental EEG. These limitations of ApEn suggest the introduction of an
alternative index, here called modified ApEn, which is based on the following
principles: oversampling is compensated, self-recurrences are ignored, a fixed
percentage of recurrences is selected and low frequency trends are removed. The
modified index allows to get more stable measurements of the complexity of the
tested simulated data and EEG. The final conclusions are that, in order to get a
reliable estimation of complexity using ApEn, parameters should be chosen within
specific ranges, data must be sampled close to the Nyquist limit and low
frequency trends should be removed. Following these indications, different
studies could be more easily compared, interpreted and replicated. Moreover, the
modified ApEn can be an interesting alternative, which extends the range of
parameters for which stable indications can be achieved.
PMID- 29942264
TI - Association Between 12 Polymorphisms of VEGF/Hypoxia/Angiogenesis Pathway Genes
and Risk of Urogenital Carcinomas: A Meta-Analysis Based on Case-Control Studies.
AB - Objective: Previous studies indicated potential associations between
polymorphisms in genes of VEGF/hypoxia/angiogenesis pathway and risk of
urogenital carcinomas However, the results were controversial and inconclusive.
Here, we conducted an in-depth meta-analysis to investigate the precise
associations between polymorphisms in VEGF/hypoxia/angiogenesis related genes and
risk of urogenital carcinomas. Methods: We searched PubMed, Web of Science,
EMBASE, and Cochrane Library to identify all eligible publications. Pooled odds
ratios (ORs) corresponding with the 95% confidence intervals (CIs) were
calculated to evaluate their associations. Subgroup analysis was conducted to
further ascertain such relationship and investigate sources of heterogeneity.
Results: In the end, a total of 96 case-control studies fulfilled the inclusion
criteria were enrolled for 12 polymorphisms in 4 VEGF/hypoxia/angiogenesis
related genes. The pooled results showed eNOS-rs2070744 polymorphism conferred a
significantly increased overall risk of urogenital carcinomas in allele,
homozygote, and recessive models, respectively. In addition, eNOS-Intron 4a/b
VNTR polymorphism was identified related to an increased risk of urogenital
carcinomas in recessive model. And VEGF-rs699947 polymorphism was also identified
an increased risk of renal cell carcinoma (RCC) in allelic, heterozygote,
dominant, homozygote, and recessive models. Conclusion: To conclude, eNOS
rs2070744 and eNOS-Intron 4a/b VNTR polymorphisms are risk factors for urogenital
carcinomas. VEGF-rs699947 polymorphism was also identified as an increased risk
factor for renal carcinoma.
PMID- 29942265
TI - Asymmetry of Hippocampus and Amygdala Defect in Subjective Cognitive Decline
Among the Community Dwelling Chinese.
AB - Background: Subjective cognitive decline (SCD) may be the first clinical sign of
Alzheimer's disease (AD). SCD individuals with normal cognition may already have
significant medial temporal lobe atrophy. However, few studies have been devoted
to exploring the alteration of left-right asymmetry with hippocampus and amygdala
in SCD. The aim of this study was to compare SCD individuals with amnestic mild
cognitive impairment (MCI) patients and the normal population for volume and
asymmetry of hippocampus, amygdala and temporal horn, and to assess their
relationship with cognitive function in elderly population living in China.
Methods: 111 SCD, 30 MCI, and 67 healthy controls (HC) underwent a standard T1
weighted MRI, from which the volumes of the hippocampus and amygdala were
calculated and compared. Then we evaluated the pattern and extent of asymmetry in
hippocampus and amygdala of these samples. Furthermore, we also investigated the
relationship between the altered brain regions and cognitive function. Results:
Among the three groups, SCD showed more depressive symptoms (p < 0.001) and
higher percentage of heart disease (16.4% vs. 35.1%, p = 0.007) than controls. In
terms of brain data, significant differences were found in the volume and
asymmetry of both hippocampus and amygdala among the three groups (P < 0.05). In
logistic analysis controlled by age, gender, education level, depression
symptoms, anxiety symptom, somatic disease and lifestyle in terms of smoking,
both SCD and MCI individuals showed significant decreased right hippocampal and
amygdala volume than controls. For asymmetry pattern, a ladder-shaped difference
of left-larger-than-right asymmetry was found in amygdala with MCI>SCD>HC, and an
opposite asymmetry of left-less-than-right pattern was found with HC>SCD>MCI in
hippocampus. Furthermore, correlation was shown between the volume of right
hippocampus and right amygdala with MMSE and MoCA in SCD group. Conclusion: Our
results supported that SCD individuals are biologically distinguishable from HC,
and this may relate to cognitive impairment, although more longitudinal studies
are need to investigate this further.Moreover, different levels of asymmetry in
hippocampus and amygdala might be a potential dividing factor to differentiate
clinical diagnosis.
PMID- 29942266
TI - Prescription and Underprescription of Clozapine in Dutch Ambulatory Care.
AB - Purpose: To our knowledge, no study has examined in a structured way the extent
of underprescription of clozapine in ambulatory patients with Non-Affective
Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients
is provided by Flexible Assertive Community Treatment (FACT) teams and by early
intervention teams. In 20 FACT teams and 3 early intervention teams we assessed
the proportion of patients who: use clozapine (type 1 patients), previously used
this drug (type 2), have an unfulfilled indication for this drug, by type of
indication (type 3), or were at least markedly psychotic, but had not yet
received two adequate treatments with other antipsychotic drugs (type 4). We
expected to find major differences between teams. To rule out that these
differences are caused by differences in severity of psychopathology, we also
calculated the proportions of patients who use clozapine given an indication at
any time (number of type 1 patients divided by the sum of type 1, 2, and 3
patients). Materials and methods: The nurse practitioner of each team identified
the patients already on clozapine. Next, using a highly-structured decision tree,
the nurse practitioner and psychiatrist assessed whether the remaining patients
had an indication for this drug. Indications were treatment-resistant positive
symptoms, tardive dyskinesia, aggression and suicidality. The severity of
positive symptoms was determined using the Clinical Global Impression
Schizophrenia Scale (CGI-SCH). Results: In the participating FACT-teams 2,286
NAPD patients were assessed. The range among teams in proportions was: type 1:
8.8-34.7% (mean: 23.0%), type 2: 0-8.2% (mean: 3.5%), type 3: 1.7-15.6% (mean:
6.9%), type 4: 1.8-16.3% (mean: 8.6%). The range in proportions of patients using
this drug given an indication was 49.0-90.9% (mean: 68.8%). These figures were
lower in early intervention teams. Conclusions: The proportion of patients in
FACT-teams who have an unfulfilled indication for clozapine is 6.9%. There were
considerable differences between teams with respect to this proportion. Almost a
third of the outpatients had at any time an indication for clozapine. If one
takes type 4 patients into account, this proportion may be higher. Registration
number: NTR5135 http://www.trialregister.nl/trialreg/index.asp.
PMID- 29942267
TI - Neural Correlates of Moral Evaluation and Psychopathic Traits in Male Multi
Problem Young Adults.
AB - Multi-problem young adults (18-27 years) present with a plethora of problems,
including varying degrees of psychopathic traits. The amygdala and ventromedial
prefrontal cortex (vmPFC) have been implicated in moral dysfunction in
psychopathy in adolescents and adults, but no studies have been performed in
populations in the transitional period to adulthood. We tested in multi-problem
young adults the hypothesis that psychopathic traits are related to amygdala and
vmPFC activity during moral evaluation. Additionally, we explored the relation
between psychopathic traits and other regions consistently implicated in moral
evaluation. Our final sample consisted of 100 multi-problem young adults and 22
healthy controls. During fMRI scanning, participants judged whether pictures
showed a moral violation on a 1-4 scale. Whole brain analysis revealed neural
correlates of moral evaluation consistent with the literature. Region of interest
analyses revealed positive associations between the affective callous-unemotional
dimension of psychopathy and activation in the left vmPFC, left superior temporal
gyrus, and left cingulate. Our results are consistent with altered vmPFC function
during moral evaluation in psychopathy, but we did not find evidence for amygdala
involvement. Our findings indicate the affective callous-unemotional trait of
psychopathy may be related to widespread altered activation patterns during moral
evaluation in multi-problem young adults.
PMID- 29942268
TI - The Relationship Between Trait Procrastination, Internet Use, and Psychological
Functioning: Results From a Community Sample of German Adolescents.
AB - Adolescents with a strong tendency for irrational task delay (i.e., high trait
procrastination) may be particularly prone to use Internet applications
simultaneously to other tasks (e.g., during homework) and in an insufficiently
controlled fashion. Both Internet multitasking and insufficiently controlled
Internet usage may thus amplify the negative mental health implications that have
frequently been associated with trait procrastination. The present study explored
this role of Internet multitasking and insufficiently controlled Internet use for
the relationship between trait procrastination and impaired psychological
functioning in a community sample of N = 818 early and middle adolescents.
Results from multiple regression analyses indicate that trait procrastination was
positively related to Internet multitasking and insufficiently controlled
Internet use. Insufficiently controlled Internet use, but not Internet
multitasking, was found to partially statistically mediate the association
between trait procrastination and adolescents' psychological functioning (i.e.,
stress, sleep quality, and relationship satisfaction with parents). The study
underlines that adolescents with high levels of trait procrastination may have an
increased risk for negative outcomes of insufficiently controlled Internet use.
PMID- 29942269
TI - Commentary: Why Don't You Go to Bed on Time? A Daily Diary Study on the
Relationships Between Chronotype, Self-Control Resources and the Phenomenon of
Bedtime Procrastination.
PMID- 29942270
TI - Virtually Being Einstein Results in an Improvement in Cognitive Task Performance
and a Decrease in Age Bias.
AB - The brain's body representation is amenable to rapid change, even though we tend
to think of our bodies as relatively fixed and stable. For example, it has been
shown that a life-sized body perceived in virtual reality as substituting the
participant's real body, can be felt as if it were their own, and that the body
type can induce perceptual, attitudinal and behavioral changes. Here we show that
changes can also occur in cognitive processing and specifically, executive
functioning. Fifteen male participants were embodied in a virtual body that
signifies super-intelligence (Einstein) and 15 in a (Normal) virtual body of
similar age to their own. The Einstein body participants performed better on a
cognitive task than the Normal body, considering prior cognitive ability (IQ),
with the improvement greatest for those with low self-esteem. Einstein embodiment
also reduced implicit bias against older people. Hence virtual body ownership may
additionally be used to enhance executive functioning.
PMID- 29942271
TI - Alexithymia Is Related to the Need for More Emotional Intensity to Identify
Static Fearful Facial Expressions.
AB - Individuals with high levels of alexithymia, a personality trait marked by
difficulties in identifying and describing feelings and an externally oriented
style of thinking, appear to require more time to accurately recognize intense
emotional facial expressions (EFEs). However, in everyday life, EFEs are
displayed at different levels of intensity and individuals with high alexithymia
may also need more emotional intensity to identify EFEs. Nevertheless, the impact
of alexithymia on the identification of EFEs, which vary in emotional intensity,
has largely been neglected. To address this, two experiments were conducted in
which participants with low (LA) and high (HA) levels of alexithymia were
assessed in their ability to identify static (Experiment 1) and dynamic
(Experiment 2) morphed faces ranging from neutral to intense EFEs. Results showed
that HA needed more emotional intensity than LA to identify static fearful - but
not happy or disgusted - faces. On the contrary, no evidence was found that
alexithymia affected the identification of dynamic EFEs. These results extend
current literature suggesting that alexithymia is related to the need for more
perceptual information to identify static fearful EFEs.
PMID- 29942272
TI - Implementation of a Positive Technology Application in Patients With Eating
Disorders: A Pilot Randomized Control Trial.
AB - Background: Positive psychological interventions (PPIs) have been suggested to
produce benefits in patients with eating disorders (ED) by improving well-being,
which might act as a buffer of the harmful effects caused by the disorder. Best
Possible Self (BPS) is a PPI which consists of writing and envisioning a future
where everything has turned out in the best possible way. In this regard,
positive technology (PT) can be of considerable benefit as it allows to implement
specific PPIs that have already shown efficacy. Objective: This study tested the
preliminary efficacy of the BPS exercise implemented through a PT application and
carried out for 1 month, in improving positive functioning measures, compared to
a control condition, in patients with ED. Follow-up effects were also explored at
1 and 3 months later. Methods: This is a pilot randomized controlled trial, with
two experimental conditions. Participants were 54 outpatients, who were receiving
ongoing specialized treatment in ED services. 29 participants were randomly
allocated to the BPS intervention and 25 to the control exercise. The sample was
composed mostly by females and the mean age was 27 years. In the intervention
group, participants had to write about their BPS. In the control group
participants had to write about their daily activities. The exercise was
conducted through the Book of Life, which is a PT application that allows users
to add multimedia materials to the written content. Measures of future
expectations, affect, dispositional optimism, hope and self-efficacy were
assessed at different time frames. Results: Findings showed that all participants
improved over time and there were no statistically significant differences
between conditions on the specific measures. These effects were not influenced by
prior levels of ED severity. Within-group effect sizes indicate a greater benefit
for the participants in the BPS condition, compared to the control condition, on
nearly all the measures. Conclusion: Results indicated that PT produced modest
improvements in patients with EDs that are receiving current treatment for ED.
More empirical attention is needed to explore the potential benefits of PPIs as
supporting tools in the prevention and treatment of EDs. Trial registration:
clinicaltrails.gov Identifier: NCT03003910, retrospectively registered December
27, 2016.
PMID- 29942273
TI - Evaluative Processing of Food Images: A Conditional Role for Viewing in
Preference Formation.
AB - Previous research suggested a role of gaze in preference formation, not merely as
an expression of preference, but also as a causal influence. According to the
gaze cascade hypothesis, the longer subjects look at an item, the more likely
they are to develop a preference for it. However, to date the connection between
viewing and liking has been investigated predominately with self-paced viewing
conditions in which the subjects were required to select certain items from
simultaneously presented stimuli on the basis of perceived visual attractiveness.
Such conditions might promote a default, but non-mandatory connection between
viewing and liking. To explore whether the connection is separable, we examined
the evaluative processing of single naturalistic food images in a 2 * 2 design,
conducted completely within subjects, in which we varied both the type of
exposure (self-paced versus time-controlled) and the type of evaluation (non
exclusive versus exclusive). In the self-paced exclusive evaluation, longer
viewing was associated with a higher likelihood of a positive evaluation.
However, in the self-paced non-exclusive evaluation, the trend reversed such that
longer viewing durations were associated with lesser ratings. Furthermore, in the
time-controlled tasks, both with non-exclusive and exclusive evaluation, there
was no significant relationship between the viewing duration and the evaluation.
The overall pattern of results was consistent for viewing times measured in terms
of exposure duration (i.e., the duration of stimulus presentation on the screen)
and in terms of actual gaze duration (i.e., the amount of time the subject
effectively gazed at the stimulus on the screen). The data indicated that viewing
does not intrinsically lead to a higher evaluation when evaluating single food
images; instead, the relationship between viewing duration and evaluation depends
on the type of task. We suggest that self-determination of exposure duration may
be a prerequisite for any influence from viewing time on evaluative processing,
regardless of whether the influence is facilitative. Moreover, the purported
facilitative link between viewing and liking appears to be limited to exclusive
evaluation, when only a restricted number of items can be included in a chosen
set.
PMID- 29942274
TI - Dynamics Matter: Recognition of Reward, Affiliative, and Dominance Smiles From
Dynamic vs. Static Displays.
AB - Smiles are distinct and easily recognizable facial expressions, yet they markedly
differ in their meanings. According to a recent theoretical account, smiles can
be classified based on three fundamental social functions which they serve:
expressing positive affect and rewarding self and others (reward smile), creating
and maintaining social bonds (affiliative smile), and negotiating social status
(dominance smiles) (Niedenthal et al., 2010; Martin et al., 2017). While there is
evidence for distinct morphological features of these smiles, their
categorization only starts to be investigated in human faces. Moreover, the
factors influencing this process - such as facial mimicry or display mode -
remain yet unknown. In the present study, we examine the recognition of reward,
affiliative, and dominance smiles in static and dynamic portrayals, and explore
how interfering with facial mimicry affects such classification. Participants (N
= 190) were presented with either static or dynamic displays of the three smile
types, whilst their ability to mimic was free or restricted via a pen-in-mouth
procedure. For each stimulus they rated the extent to which the expression
represents a reward, an affiliative, or a dominance smile. Higher than chance
accuracy rates revealed that participants were generally able to differentiate
between the three smile types. In line with our predictions, recognition
performance was lower in the static than dynamic condition, but this difference
was only significant for affiliative smiles. No significant effects of facial
muscle restriction were observed, suggesting that the ability to mimic might not
be necessary for the distinction between the three functional smiles. Together,
our findings support previous evidence on reward, affiliative, and dominance
smiles by documenting their perceptual distinctiveness. They also replicate
extant observations on the dynamic advantage in expression perception and suggest
that this effect may be especially pronounced in the case of ambiguous facial
expressions, such as affiliative smiles.
PMID- 29942275
TI - Distinct Patterns of Cognitive Conflict Dynamics in Promise Keepers and Promise
Breakers.
AB - On a daily basis, we see how different people can be in keeping or breaking a
given promise. However, we know very little about the cognitive conflict dynamics
that underlie the decision to keep or break a promise and whether this is shaped
by inter-individual variability. In order to fill this gap, we applied an
ecologically valid promise decision task with real monetary consequences for all
involved interaction partners and used mouse tracking to identify the dynamic, on
line cognitive processes that underlie the decision to keep or break a promise.
Our findings revealed that on average, the process of breaking a promise is
associated with largely curved mouse trajectories, while the process of keeping a
promise was not, indicating that breaking a promise is associated with a larger
conflict. Interestingly, however, this conflict pattern was strongly shaped by
individual differences. Individuals who always kept their promises did not show
any signs of conflict (i.e., straight mouse trajectories), indicating that they
were not tempted by the monetary benefits associated with breaking the promise.
In contrast, individuals who did not always keep their promise exhibited a large
conflict (i.e., curved mouse trajectories), irrespective of whether they broke or
kept their promise. A possible interpretation of these findings is that these
individuals were always tempted by the unchosen decision option - the desire to
act in a fair manner when breaking the promise and the monetary benefits when
keeping the promise. This study provides the first piece of evidence that there
are substantial inter-individual differences in cognitive conflict dynamics that
underlie the decision to keep or break promises and that mouse tracking is able
to illuminate important insights into individual differences in complex human's
decision processes.
PMID- 29942276
TI - A Cross-Sectional and Longitudinal Study of Novel Metaphor and Metonymy
Comprehension in Children, Adolescents, and Adults With Autism Spectrum Disorder.
AB - Previous studies have shown that comprehension of figurative language is impaired
in individuals with autism spectrum disorder (ASD). However, most studies have
focused on lexicalized expressions and have only examined performance at one
particular point in time, without examining how performance changes over
development. The current study examined the comprehension of novel metaphor and
metonymy in individuals with ASDs from a large age range, using both a cross
sectional (Experiment 1) and longitudinal design (Experiment 2). Performance in
the ASD group was lower compared to typically developing (TD) controls, across
all ages. Importantly, the results from Experiments 1 and 2 showed that, although
chronological age was not a good predictor for performance of either novel
metaphor or metonymy in the cross-sectional design, performance improved when
longitudinal data was considered. Correlations between vocabulary knowledge,
visuo-spatial abilities and figurative language comprehension abilities were also
explored.
PMID- 29942277
TI - Eye-Tracking Provides a Sensitive Measure of Exploration Deficits After Acute
Right MCA Stroke.
AB - The eye-tracking study aimed at assessing spatial biases in visual exploration in
patients after acute right MCA (middle cerebral artery) stroke. Patients affected
by unilateral neglect show less functional recovery and experience severe
difficulties in everyday life. Thus, accurate diagnosis is essential, and
specific treatment is required. Early assessment is of high importance as
rehabilitative interventions are more effective when applied soon after stroke.
Previous research has shown that deficits may be overlooked when classical paper
and-pencil tasks are used for diagnosis. Conversely, eye-tracking allows direct
monitoring of visual exploration patterns. We hypothesized that the analysis of
eye-tracking provides more sensitive measures for spatial exploration deficits
after right middle cerebral artery stroke. Twenty-two patients with right MCA
stroke (median 5 days after stroke) and 28 healthy controls were included.
Lesions were confirmed by MRI/CCT. Groups performed comparably in the Mini-Mental
State Examination (patients and controls median 29) and in a screening of
executive functions. Eleven patients scored at ceiling in neglect screening
tasks, 11 showed minimal to severe signs of unilateral visual neglect. An overlap
plot based on MRI and CCT imaging showed lesions in the temporo-parieto-frontal
cortex, basal ganglia, and adjacent white matter tracts. Visual exploration was
evaluated in two eye-tracking tasks, one assessing free visual exploration of
photographs, the other visual search using symbols and letters. An index of
fixation asymmetries proved to be a sensitive measure of spatial exploration
deficits. Both patient groups showed a marked exploration bias to the right when
looking at complex photographs. A single case analysis confirmed that also most
of those patients who showed no neglect in screening tasks performed outside the
range of controls in free exploration. The analysis of patients' scoring at
ceiling in neglect screening tasks is of special interest, as possible deficits
may be overlooked and thus remain untreated. Our findings are in line with other
studies suggesting considerable limitations of laboratory screening procedures to
fully appreciate the occurrence of neglect symptoms. Future investigations are
needed to explore the predictive value of the eye-tracking index and its validity
in everyday situations.
PMID- 29942279
TI - The Gain-Time Constant Product Quantifies Total Vestibular Output in Bilateral
Vestibular Loss.
AB - Patients with inner ear damage associated with bilateral vestibular impairment
often ask "how much damage do I have." Although there are presently three
clinical methods of measuring semicircular canal vestibular function;
electronystagmography (ENG or VENG), rotatory chair and video head-impulse (VHIT)
testing; none of these methods provides a method of measuring total vestibular
output. Theory suggests that the slow cumulative eye position can be derived from
the rotatory chair test by multiplying the high frequency gain by the time
constant, or the "GainTc product." In this retrospective study, we compared the
GainTc in three groups, 30 normal subjects, 25 patients with surgically induced
unilateral vestibular loss, and 24 patients with absent or nearly absent
vestibular responses due to gentamicin exposure. We found that the GainTc product
correlated better with remaining vestibular function than either the gain or the
time constant alone. The fraction of remaining vestibular function was predicted
by the equation R = (GainTc/11.3) - 0.6. We suggest that the GainTc product
answers the question "how much damage do I have," and is a better measure than
other clinical tests of vestibular function.
PMID- 29942278
TI - Effects of Rhythmic Auditory Cueing in Gait Rehabilitation for Multiple
Sclerosis: A Mini Systematic Review and Meta-Analysis.
AB - Rhythmic auditory cueing has been shown to enhance gait performance in several
movement disorders. The "entrainment effect" generated by the stimulations can
enhance auditory motor coupling and instigate plasticity. However, a consensus as
to its influence over gait training among patients with multiple sclerosis is
still warranted. A systematic review and meta-analysis was carried out to analyze
the effects of rhythmic auditory cueing in studies gait performance in patients
with multiple sclerosis. This systematic identification of published literature
was performed according to PRISMA guidelines, from inception until Dec 2017, on
online databases: Web of science, PEDro, EBSCO, MEDLINE, Cochrane, EMBASE, and
PROQUEST. Studies were critically appraised using PEDro scale. Of 602 records,
five studies (PEDro score: 5.7 +/- 1.3) involving 188 participants (144
females/40 males) met our inclusion criteria. The meta-analysis revealed
enhancements in spatiotemporal parameters of gait i.e., velocity (Hedge's g:
0.67), stride length (0.70), and cadence (1.0), and reduction in timed 25 feet
walking test (-0.17). Underlying neurophysiological mechanisms, and clinical
implications are discussed. This present review bridges the gaps in literature by
suggesting application of rhythmic auditory cueing in conventional rehabilitation
approaches to enhance gait performance in the multiple sclerosis community.
PMID- 29942280
TI - Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus Improves
Patient Outcomes: A Nationwide Hospital-Based Survey in Japan.
AB - Background and Purpose: This study aimed to investigate the efficacy of
cerebrospinal fluid shunt intervention for idiopathic normal pressure
hydrocephalus (iNPH) using data from a nationwide epidemiological survey in
Japan. Methods: We conducted a cross-sectional study using data from a nationwide
epidemiological survey performed in Japan. Propensity score matching was used to
select 874 patients from 1,423 patients aged >=60 years, who were diagnosed with
iNPH based on clinical guidelines following a hospital visit in 2012. Patients
who experienced an improvement of at least 1 modified Rankin Scale (mRS) grade
after the intervention were classified as "improved," while the remaining
patients were classified as "non-improved." In the shunt intervention (n = 437)
and non-shunt intervention (n = 437) groups, the differences in mRS grade
improvement were analyzed using the Mann-Whitney U-test. Finally, we examined
subjects in the shunt intervention group (n = 974) to compare the outcomes and
complications of ventriculoperitoneal (VP) shunt (n = 417) with lumboperitoneal
(LP) shunt (n = 540). Results: We examined subjects with iNPH to compare the non
shunt intervention group to the shunt intervention group following adjustment for
age and mRS grade at baseline by propensity score matching (0.31-0.901). The mRS
grade (mean [SD]) was found to improve with non-shunt intervention (2.46 [0.88])
and shunt intervention (1.93 [0.93]) (p < 0.001) in iNPH patients. The mRS
outcome score and complications comparison between the VP and LP shunt groups did
not show significant difference. Conclusions: In this study, analysis of the
efficacy of shunts for possible iNPH conducted in Japan indicated a significant
improvement in the mRS grade between baseline and outcome within 1 year,
regardless of the surgical technique, and shunt intervention was found to be
effective.
PMID- 29942281
TI - Betahistine Treatment in a Cat Model of Vestibular Pathology: Pharmacokinetic and
Pharmacodynamic Approaches.
AB - This study is a pharmacokinetic (PK) and pharmacodynamics (PD) approach using
betahistine doses levels in unilateral vestibular neurectomized cats (UVN)
comparable to those used in humans for treating patients with Meniere's disease.
The aim is to investigate for the first time oral betahistine administration (0.2
and 2 mg/kg/day) with plasma concentrations of betahistine and its major
metabolite 2-pyridylacetic acid (2-PAA) (N = 9 cats), the time course of posture
recovery (N = 13 cats), and the regulation of the enzyme synthesizing histamine
(histidine decarboxylase: HDC) in the tuberomammillary nuclei (TMN) of UVN
treated animals (N = the same 13 cats plus 4 negative control cats). In addition
the effect of co-administration of the lower betahistine dose (0.2 mg/kg/day) and
selegiline (1 mg/kg/day), an inhibitor of the monamine oxidase B (MAOBi)
implicated in betahistine catabolism was investigated. The PK parameters were the
peak concentration (Cmax), the time when the maximum concentration is reached
(Tmax) for both betahistine and 2-PAA and the area under the curve (AUC). The PD
approach consisted at quantifying the surface support area, which is a good
estimation of posture recovery. The plasma concentration-time-profiles of
betahistine and 2-PAA in cats were characterized by early Cmax-values followed by
a phase of rapid decrease of plasma concentrations and a final long lasting low
level of plasma concentrations. Co administration of selegiline and betahistine
increased values of Cmax and AUC up to 146- and 180-fold, respectively. The
lowest dose of betahistine (0.2 mg/kg) has no effects on postural function
recovery but induced an acute symptomatic effect characterized by a fast balance
improvement (4-6 days). The higher dose (2 mg/kg) and the co-administration
treatment induced both this acute effect plus a significant acceleration of the
recovery process. The histaminergic activity of the neurons in the TMN was
significantly increased under treatment with the 2 mg/kg betahistine daily dose,
but not with the lower dose alone or in combination with selegiline. The results
show for the first time that faster balance recovery in UVN treated cats is
accompanied with high plasma concentrations of betahistine and 2-PAA, and
upregulation of HDC immunopositive neurons in the TMN. The higher betahistine
dose gives results similar to those obtained with the lower dose when co
administrated with an inhibitor of betahistine metabolism, selegiline. From a
clinical point of view, the study provides new perspectives for Meniere's disease
treatment, regarding the daily betahistine dose that should be necessary for fast
and slow metabolizers.
PMID- 29942282
TI - Hypothermia Reduces Mortality, Prevents the Calcium Plateau, and Is
Neuroprotective Following Status Epilepticus in Rats.
AB - Status Epilepticus (SE) is a major neurological emergency and is considered a
leading cause of Acquired Epilepsy (AE). We have shown that SE produces neuronal
injury and prolonged alterations in hippocampal calcium levels ([Ca2+]i) that may
underlie the development of AE. Interventions preventing the SE-induced Ca2+
plateau could therefore prove to be beneficial in lowering the development of AE
after SE. Hypothermia is used clinically to prevent neurological complications
associated with Traumatic Brain Injury, cardiac arrest, and stroke. Here, we
investigated whether hypothermia prevented the development of Ca2+ plateau
following SE. SE was induced in hippocampal neuronal cultures (HNC) by exposing
them to no added MgCl2 solution for 3 h. To terminate SE, low Mg2+ solution was
washed off with 31 degrees C (hypothermic) or 37 degrees C (normothermic)
physiological recording solution. [Ca2+]i was estimated with ratiometric Fura-2
imaging. HNCs washed with hypothermic solution exhibited [Ca2+]i ratios, which
were significantly lower than ratios obtained from HNCs washed with normothermic
solution. For in vivo SE, the rat pilocarpine (PILO) model was used. Moderate
hypothermia (30-33 degrees C) in rats was induced at 30-min post-SE using chilled
ethanol spray in a cold room. Hypothermia following PILO-SE significantly reduced
mortality. Hippocampal neurons isolated from hypothermia-treated PILO SE rats
exhibited [Ca2+]i ratios which were significantly lower than ratios obtained from
PILO SE rats. Hypothermia also provided significant neuroprotection against SE
induced delayed hippocampal injury as characterized by decreased FluoroJade C
labeling in hypothermia-treated PILO SE rats. We previously demonstrated that
hypothermia reduced Ca2+ entry via N-methyl-D-aspartate and ryanodine receptors
in HNC. Together, our studies indicate that by targeting these two receptor
systems hypothermia could interfere with epileptogenesis and prove to be an
effective therapeutic intervention for reducing SE-induced AE.
PMID- 29942283
TI - Tachykinin-3 Genes and Peptides Characterized in a Basal Teleost, the European
Eel: Evolutionary Perspective and Pituitary Role.
AB - In mammals, neurokinin B (NKB) is a short peptide encoded by the gene tac3. It is
involved in the brain control of reproduction by stimulating gonadotropin
releasing hormone (GnRH) neurons, mainly via kisspeptin. We investigated tac3
genes and peptides in a basal teleost, the European eel, which shows an atypical
blockade of the sexual maturation at a prepubertal stage. Two tac3 paralogous
genes (tac3a and tac3b) were identified in the eel genome, each encoding two
peptides (NKBa or b and NKB-related peptide NKB-RPa or b). Amino acid sequence of
eel NKBa is identical to human NKB, and the three others are novel peptide
sequences. The four eel peptides present the characteristic C-terminal tachykinin
sequence, as well as a similar alpha helix 3D structure. Tac3 genes were
identified in silico in 52 species of vertebrates, and a phylogeny analysis was
performed on the predicted TAC3 pre-pro-peptide sequences. A synteny analysis was
also done to further assess the evolutionary history of tac3 genes. Duplicated
tac3 genes in teleosts likely result from the teleost-specific whole genome
duplication (3R). Among teleosts, TAC3b precursor sequences are more divergent
than TAC3a, and a loss of tac3b gene would have even occurred in some teleost
lineages. NKB-RP peptide, encoded beside NKB by tac3 gene in actinopterygians and
basal sarcopterygians, would have been lost in ancestral amniotes. Tissue
distribution of eel tac3a and tac3b mRNAs showed major expression of both
transcripts in the brain especially in the diencephalon, as analyzed by specific
qPCRs. Human NKB has been tested in vitro on primary culture of eel pituitary
cells. Human NKB dose-dependently inhibited the expression of lhbeta, while
having no effect on other glycoprotein hormone subunits (fshbeta, tshbeta, and
gpalpha) nor on gh. Human NKB also dose-dependently inhibited the expression of
GnRH receptor (gnrh-r2). The four eel peptides have been synthesized and also
tested in vitro. They all inhibited the expression of both lhbeta and of gnrh-r2.
This reveals a potential dual inhibitory role of the four peptides encoded by the
two tac3 genes in eel reproduction, exerted at the pituitary level on both
luteinizing hormone and GnRH receptor.
PMID- 29942284
TI - Augmented Fibroblast Growth Factor-23 Secretion in Bone Locally Contributes to
Impaired Bone Mineralization in Chronic Kidney Disease in Mice.
AB - Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic disorder
of mineral and bone metabolism caused by CKD. Impaired bone mineralization
together with increased bony secretion of fibroblast growth factor-23 (FGF23) are
hallmarks of CKD-MBD. We recently showed that FGF23 suppresses the expression of
tissue nonspecific alkaline phosphatase (TNAP) in bone cells by a Klotho
independent, FGF receptor-3-mediated signaling axis, leading to the accumulation
of the mineralization inhibitor pyrophosphate. Therefore, we hypothesized that
excessive FGF23 secretion may locally impair bone mineralization in CKD-MBD. To
test this hypothesis, we induced CKD by 5/6 nephrectomy in 3-month-old wild-type
(WT) mice and Fgf23-/-/VDRDelta/Delta (Fgf23/VDR) compound mutant mice maintained
on a diet enriched with calcium, phosphate, and lactose. Eight weeks postsurgery,
WT CKD mice were characterized by reduced bone mineral density at the axial and
appendicular skeleton, hyperphosphatemia, secondary hyperparathyroidism,
increased serum intact Fgf23, and impaired bone mineralization as evidenced by
bone histomorphometry. Laser capture microdissection in bone cryosections showed
that both osteoblasts and osteocytes contributed to the CKD-induced increase in
Fgf23 mRNA abundance. In line with our hypothesis, osteoblastic and osteocytic
activity of alkaline phosphatase was reduced, and bone pyrophosphate
concentration was ~2.5-fold higher in CKD mice, relative to Sham controls. In
Fgf23/VDR compound mice lacking Fgf23, 5/6-Nx induced secondary
hyperparathyroidism and bone loss. However, 5/6-Nx failed to suppress TNAP
activity, and bone pyrophosphate concentrations remained unchanged in Fgf23/VDR
CKD mice. Collectively, our data suggest that elevated Fgf23 production in bone
contributes to the mineralization defect in CKD-MBD by auto-/paracrine
suppression of TNAP and subsequent accumulation of pyrophosphate in bone. Hence,
our study has identified a novel mechanism involved in the pathogenesis of CKD
MBD.
PMID- 29942285
TI - Glucose Metabolism in Children With Growth Hormone Deficiency.
AB - Background: The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis has
a fundamental impact on glucose metabolism. Therefore, both untreated GH
deficiency (GHD) and GH treatment (GHT) may be associated with some metabolic
alterations, although the abnormalities of glucose metabolism have been
investigated by relatively few studies as main outcomes. Aim: The present review
summarizes the available data on glucose metabolism in children with GHD,
providing an overview of the current state of the art in order to better clarify
the real metabolic impact of GHD and GHT. Methods: Among all the existing
studies, we evaluated all original studies that fulfilled our criteria for
analysis reporting parameters of glucose metabolism as the primary or secondary
objective. Results: The reported impact of GHD per se on glucose metabolism is
quite homogeneous, with the majority of studies reporting no significant
difference in metabolic parameters between GHD children and controls. Conversely,
GHT proves to be more frequently associated with a subtle form of insulin
resistance, while both fasting glucose and HbA1c levels remain almost always
within the normal range. Conclusion: The different methods to study glucose
metabolism, the heterogeneity of the populations evaluated, the different doses
of GH used together with the variable duration of follow-up may be responsible
for discrepancy in the results. Long-term longitudinal studies having glucose
homeostasis as their primary outcome are still needed in order better to clarify
the real metabolic impact of GHD and GHT in children.
PMID- 29942286
TI - A Study on the Association Between Polymorphisms in the Cytochrome P450 Family 17
Subfamily A Member 1 Gene Region and Type 2 Diabetes Mellitus in Han Chinese.
AB - Background: Cytochrome P450 family 17 subfamily A member 1 (CYP17A1) gene encodes
a key enzyme in the synthesis and metabolism of steroid hormones and has been
associated with various factors, such as hypertension, insulin resistance, and
polycystic ovary syndrome. However, whether the gene was associated with type 2
diabetes mellitus (T2DM) has not been reported yet. Therefore, we sought to
investigate whether CYP17A1 was associated with T2DM and related traits among Han
Chinese. Methods: Three tagging single nucleotide polymorphisms (rs1004467,
rs17115149, and rs12413409), in the CYP17A1 gene region were selected and
genotyped in a case-control study that included 440 diabetes and 1,320 control
subjects. Effects of genetic loci were studied using univariate unconditional
logistic regression and multivariate logistic regression analysis adjusted for
age, sex, family history, body mass index, smoking, and drinking. Bioinformatics
analysis was also conducted using the GEO DataSets and PROMO database to gain
hints of possible mechanism. Results: Rs17115149 and rs12413409 polymorphisms
were significantly associated with the risk of T2DM, even after adjusting for
age, sex, family history, body mass index, smoking, and drinking. In stratified
analyses, rs1004467 and rs12413409 showed significant association with T2DM in
the older age group (>=65 years) and, in the case of rs12413409, the risk of T2DM
was significant in men but not in women. Rs17115149 had significant association
with T2DM in the hypertension subgroup, and rs12413409 in the non-hypertension
subgroup. Moreover, rs12413409 showed significant association with plasma glucose
levels in the recessive model (P = 0.020) among subjects not taking hypoglycemic
measures. Bioinformatics analysis revealed significantly higher CYP17A1 gene
expression in T2DM patients compared to healthy controls. Finally, the mutant T
allele of the rs17115149 polymorphism allowed binding to the RBP-Jkappa
transcription factor. Conclusion: This is the first report to identify that
variants rs1004467, rs17115149, and rs12413409 of CYP17A1, are related to plasma
glucose levels and T2DM among Han Chinese. Our results suggest that CYP17A1 might
constitute a risk gene for progression to T2DM.
PMID- 29942287
TI - Detection of the Entomopathogenic Fungus Beauveria bassiana in the Rhizosphere of
Wound-Stressed Zea mays Plants.
AB - Entomopathogenic fungi from the genus Beauveria (Vuillemin) play an important
role in controlling insect populations and have been increasingly utilized for
the biological control of insect pests. Various studies have reported that
Beauveria bassiana (Bals.), Vuill. also has the ability to colonize a broad range
of plant hosts as endophytes without causing disease but while still maintaining
the capacity to infect insects. Beauveria is often applied as an inundative spore
application, but little research has considered how plant colonization may alter
the ability to persist in the environment. The aim of this study was to
investigate potential interactions between B. bassiana and Zea mays L. (maize) in
the rhizosphere following inoculation, in order to understand the factors that
may affect environmental persistence of the fungi. The hypothesis was that
different isolates of B. bassiana have the ability to colonize maize roots and/or
rhizosphere soil, resulting in effects to the plant microbiome. To test this
hypothesis, a two-step nested PCR protocol was developed to find and amplify
Beauveria in planta or in soil; based on the translation elongation factor 1
alpha (ef1alpha) gene. The nested protocol was also designed to enable Beauveria
species differentiation by sequence analysis. The impact of three selected B.
bassiana isolates applied topically to roots on the rhizosphere soil community
structure and function were consequently assessed using denaturing gradient gel
electrophoresis (DGGE) and MicroRespTM techniques. The microbial community
structure and function were not significantly affected by the presence of the
isolates, however, retention of the inocula in the rhizosphere at 30 days after
inoculation was enhanced when plants were subjected to intensive wounding of
foliage to crudely simulate herbivory. The plant defense response likely changed
under wound stress resulting in the apparent recruitment of Beauveria in the
rhizosphere, which may be an indirect defensive strategy against herbivory and/or
the result of induced systemic susceptibility in maize enabling plant
colonization.
PMID- 29942288
TI - The ColRS-Regulated Membrane Protein Gene XAC1347 Is Involved in Copper
Homeostasis and hrp Gene Expression in Xanthomonas citri subsp. citri.
AB - Xanthomonas citri subsp. citri (Xcc) is the major causal agent of citrus canker
disease. The XAC1347 gene, which encodes a conserved membrane protein in Xcc, is
required for virulence during infection. However, the molecular events mediated
by XAC1347 remain unclear. In this study, we reported that XAC1347 gene is
positively regulated by two component regulatory system ColRS and required for
type III secretion system function. A non-polar deletion mutant of the XAC1347
gene resulted in a Hrp minus phenotype in plants and reduced copper homeostasis.
Real-time PCR experiments indicated that XAC1347 gene is induced by copper ions.
The expression levels of representative genes from four hrp operons, including
hrpB1, hrcV, hrpF, and hrpD6, were reduced in XAC1347 mutant, indicating that
XAC1347 is involved hrp gene expression.
PMID- 29942289
TI - Putting the Mess in Order: Aspergillus welwitschiae (and Not A. niger) Is the
Etiological Agent of Sisal Bole Rot Disease in Brazil.
AB - Approximately 75% of the worldwide production of hard natural fibers originates
from sisal, an industrial crop from arid and semiarid tropical regions. Brazil is
the world's largest producer of sisal fiber, accounting for more than 40% of the
worldwide production, and sisal bole rot disease has been the main phytosanitary
problem of this crop. All previous studies reporting Aspergillus niger as the
causal agent of the disease were based on the morphological features of fungal
isolates from infected plant tissues in pure cultures. Black aspergilli are one
of the most complex and difficult groups to classify and identify. Therefore, we
performed an integrative analysis of this disease based on the isolation of black
aspergilli from the endospheres and soils in the root zones of symptomatic adult
plants, in vivo pathogenicity tests, histopathology of symptomatic plants, and
molecular phylogeny and worldwide genetic variability of the causal agent. All
sisal isolates were pathogenic and unequivocally produced symptoms of bole rot
disease in healthy plants. In all tree-based phylogenetic methods used, a
monophyletic group formed by A. welwitschiae along with all sisal isolates was
retrieved. Ten A. welwitschiae haplotypes have been identified in the world, and
three occur in the largest sisal-producing area. Most of the isolates are from a
unique haplotype, present in only the sisal-producing region. A. welwitschiae
destroyed parenchymatic and vascular cylinder cells and induced the necrosis of
internal stem tissues. Therefore, sisal bole disease is probably the consequence
of a saprotrophic fungus that opportunistically invades sisal plants and behaves
as a typical necrotrophic pathogen.
PMID- 29942290
TI - The Ferredoxin-Like Proteins HydN and YsaA Enhance Redox Dye-Linked Activity of
the Formate Dehydrogenase H Component of the Formate Hydrogenlyase Complex.
AB - Formate dehydrogenase H (FDH-H) and [NiFe]-hydrogenase 3 (Hyd-3) form the
catalytic components of the hydrogen-producing formate hydrogenlyase (FHL)
complex, which disproportionates formate to H2 and CO2 during mixed acid
fermentation in enterobacteria. FHL comprises minimally seven proteins and little
is understood about how this complex is assembled. Early studies identified a
ferredoxin-like protein, HydN, as being involved in FDH-H assembly into the FHL
complex. In order to understand how FDH-H and its small subunit HycB, which is
also a ferredoxin-like protein, attach to the FHL complex, the possible roles of
HydN and its paralogue, YsaA, in FHL complex stability and assembly were
investigated. Deletion of the hycB gene reduced redox dye-mediated FDH-H activity
to approximately 10%, abolished FHL-dependent H2-production, and reduced Hyd-3
activity. These data are consistent with HycB being an essential electron
transfer component of the FHL complex. The FDH-H activity of the hydN and the
ysaA deletion strains was reduced to 59 and 57% of the parental, while the double
deletion reduced activity of FDH-H to 28% and the triple deletion with hycB to
1%. Remarkably, and in contrast to the hycB deletion, the absence of HydN and
YsaA was without significant effect on FHL-dependent H2-production or total Hyd-3
activity; FDH-H protein levels were also unaltered. This is the first description
of a phenotype for the E. coli ysaA deletion strain and identifies it as a novel
factor required for optimal redox dye-linked FDH-H activity. A ysaA deletion
strain could be complemented for FDH-H activity by hydN and ysaA, but the hydN
deletion strain could not be complemented. Introduction of these plasmids did not
affect H2 production. Bacterial two-hybrid interactions showed that YsaA, HydN,
and HycB interact with each other and with the FDH-H protein. Further novel
anaerobic cross-interactions of 10 ferredoxin-like proteins in E. coli were also
discovered and described. Together, these data indicate that FDH-H activity
measured with the redox dye benzyl viologen is the sum of the FDH-H protein
interacting with three independent small subunits and suggest that FDH-H can
associate with different redox-protein complexes in the anaerobic cell to supply
electrons from formate oxidation.
PMID- 29942291
TI - Comparative Genomics of Lactobacillus acidipiscis ACA-DC 1533 Isolated From
Traditional Greek Kopanisti Cheese Against Species Within the Lactobacillus
salivarius Clade.
AB - Lactobacillus acidipiscis belongs to the Lactobacillus salivarius clade and it is
found in a variety of fermented foods. Strain ACA-DC 1533 was isolated from
traditional Greek Kopanisti cheese and among the available L. acidipiscis genomes
it is the only one with a fully sequenced chromosome. L. acidipiscis strains
exhibited a high degree of conservation at the genome level. Investigation of the
distribution of prophages and Clustered Regularly Interspaced Short Palindromic
Repeats (CRISPRs) among the three strains suggests the potential existence of
lineages within the species. Based on the presence/absence patterns of these
genomic traits, strain ACA-DC 1533 seems to be more related to strain JCM 10692T
than strain KCTC 13900. Interestingly, strains ACA-DC 1533 and JCM 10692T which
lack CRISPRs, carry two similar prophages. In contrast, strain KCTC 13900 seems
to have acquired immunity to these prophages according to the sequences of
spacers in its CRISPRs. Nonetheless, strain KCTC 13900 has a prophage that is
absent from strains ACA-DC 1533 and JCM 10692T. Furthermore, comparative genomic
analysis was performed among L. acidipiscis ACA-DC 1533, L. salivarius UCC118 and
Lactobacillus ruminis ATCC 27782. The chromosomes of the three species lack long
range synteny. Important differences were also determined in the number of
glycobiome related proteins, proteolytic enzymes, transporters, insertion
sequences and regulatory proteins. Moreover, no obvious genomic traits supporting
a probiotic potential of L. acidipiscis ACA-DC 1533 were detected when compared
to the probiotic L. salivarius UCC118. However, the existence of more than one
glycine-betaine transporter within the genome of ACA-DC 1533 may explain the
ability of L. acidipiscis to grow in fermented foods containing high salt
concentrations. Finally, in silico analysis of the L. acidipiscis ACA-DC 1533
genome revealed pathways that could underpin the production of major volatile
compounds during the catabolism of amino acids that may contribute to the typical
piquant flavors of Kopanisti cheese.
PMID- 29942292
TI - Actinobacteria Associated With Arbuscular Mycorrhizal Funneliformis mosseae
Spores, Taxonomic Characterization and Their Beneficial Traits to Plants:
Evidence Obtained From Mung Bean (Vigna radiata) and Thai Jasmine Rice (Oryza
sativa).
AB - In this study, we report on the isolation of actinobacteria obtained from spores
of Funneliformis mosseae and provide evidence for their potential in agricultural
uses as plant growth promoters in vitro and in vivo. Actinobacteria were isolated
from spores of F. mosseae using the dilution plate technique and media designed
for the selective isolation of members of specific actinobacterial taxa. Six
strains namely 48, S1, S3, S4, S4-1 and SP, were isolated and identified based
on16S rRNA gene sequences. Phylogenetic analysis showed that isolate SP belonged
to the genus Pseudonocardia with P. nantongensis KLBMP 1282T as its closest
neighbor. The remaining isolates belonged to the genus Streptomyces. Two
isolates, 48 and S3 were most closely related to S. thermocarboxydus DSM 44293T.
Isolates S4 and S4-1 shared the highest 16S RNA gene similarity with S. pilosus
NBRC 127772T. Isolate S1 showed its closest relationship with the type strain of
S. spinoverrucosus NBRC14228T. The ability of these isolates to produce indole-3
acetic acid (IAA), siderophores and the ability to solubilize phosphate in vitro
were examined. All isolates produced siderophores, four isolates produced IAA and
two isolates solubilized inorganic phosphate at varying levels. S.
thermocarboxydus isolate S3 showed the highest IAA production with high
activities of phosphate solubilization and siderophore production. The
inoculation of mung beans (Vigna radiata) with this strain resulted in a
significant increase in fresh weight, root length and total length as an effect
of IAA production. In an experiment with rice (Oryza sativa), S. thermocarboxydus
isolate S3 promoted the growth of rice plants grown in low nutritional soil under
induced drought stress. This report supports the view that the inoculation of
rice with plant growth promoting actinobacteria mitigates some adverse effects of
low nutrient and drought stress on rice.
PMID- 29942293
TI - The Response Patterns of Arbuscular Mycorrhizal and Ectomycorrhizal Symbionts
Under Elevated CO2: A Meta-Analysis.
AB - Elevated carbon dioxide (eCO2), a much-discussed topic in global warming,
influences development and functions of mycorrhizal fungi and plants. However,
due to the inconsistent results reported in various publications, the response
patterns of symbionts associated with the arbuscular mycorrhizal (AM) or with
ectomycorrhizal (ECM) fungi to eCO2 remains still unclear. Therefore, we
performed a meta-analysis to identify how eCO2 affected mycorrhizal fungi and if
there is a significant different response between AM and ECM symbionts. Our
results demonstrated that eCO2 increased mycorrhizal plants biomass (+26.20%),
nutrient contents [+2.45% in nitrogen (N), and +10.66% in phosphorus (P)] and
mycorrhizal fungal growth (+22.87% in extraradical hyphal length and +21.77% in
mycorrhizal fungal biomass), whereas plant nutrient concentrations decreased (
11.86% in N and -12.01% in P) because the increase in plant biomass was greater
than that in nutrient content. The AM plants exhibited larger increases in their
biomass (+33.90%) and in their N (+21.99%) and P contents (+19.48%) than did the
ECM plants (+20.57% in biomass, -4.28% in N content and -13.35% in P content).
However, ECM fungi demonstrated increased responses of mycorrhizal fungal biomass
(+29.98%) under eCO2 compared with AM fungi (+6.61%). These data indicate
different patterns in the growth of AM and ECM symbionts under eCO2: AM symbionts
contributed more to plant growth, while ECM symbionts were more favorable to
mycorrhizal fungal growth. In addition, the responses of plant biomass to eCO2
showed no significant difference between short-term and long-term groups, whereas
a significant difference in the responses of mycorrhizal fungal growth was found
between the two groups. The addition of N increased plant growth but decreased
mycorrhizal fungal abundance, and P addition increased total plant biomass and
extraradical hyphal length, but shoot biomass largely increased in low P
conditions. Mixtures of mycorrhizal fungi affected the total plant and root
biomasses more than a single mycorrhizal fungus. Clarifying the different
patterns in AM and ECM symbionts under eCO2 would contribute to a better
understanding of the interactions between mycorrhizal fungi and plant symbionts
under the conditions of global climate change as well as of the coevolution of
flora with Earth's environment.
PMID- 29942294
TI - Reducing Water Availability Impacts the Development of the Arbuscular Mycorrhizal
Fungus Rhizophagus irregularis MUCL 41833 and Its Ability to Take Up and
Transport Phosphorus Under in Vitro Conditions.
AB - Climate change scenarios predict a higher variability in rainfall and an
increased risk of water deficits during summers for the coming decades. For this
reason, arbuscular mycorrhizal fungi (AMF) and their mitigating effects on
drought stress in plants are increasingly considered in crop management. However,
the impact of a decrease in water availability on the development of AMF and
their ability to take up and transport inorganic phosphorus (Pi) to their hosts
remain poorly explored. Here, Medicago truncatula plantlets were grown in
association with Rhizophagus irregularis MUCL 41833 in bi-compartmented Petri
plates. The system consisted in associating the plant and AMF in a root
compartment (RC), allowing only the hyphae to extend in a root-free hyphal
compartment (HC). Water availability in the HC was then lowered by increasing the
concentration of polyethylene glycol-8000 (PEG-8000) from 0 to 10, 25, and 50 g L
1 (corresponding to a slight decrease in water potential of -0.024, -0.025,
0.030, and -0.056 Mpa, respectively). Hyphal growth, spore production and
germination were severely impaired at the lowest water availability. The dynamics
of Pi uptake by the AMF was also impacted, although total Pi uptake evaluated
after 24 h stayed unchanged. The percentage of metabolically active extraradical
hyphae remained above 70%. Finally, at the lowest water availability, a higher P
concentration was observed in the shoots of M. truncatula. At reduced water
availability, the extraradical mycelium (ERM) development was impacted,
potentially limiting its capacity to explore a higher volume of soil. Pi uptake
was slowed down but not prevented. The sensitivity of R. irregularis MUCL 41833
to a, even small, decrease in water availability contrasted with several studies
reporting tolerance of AMF to drought. This suggests a species or strain
dependent effect and support the necessity to compare the impact of water
availability on morpho-anatomy, nutrient uptake and transport capacities of
other, potentially more drought-tolerant (e.g., isolated from dry environments)
AMF.
PMID- 29942295
TI - In Vitro Activity of Tedizolid, Dalbavancin, and Ceftobiprole Against Clostridium
difficile.
AB - Background:Clostridium difficile (C. difficile) is a major nosocomial pathogen
that colonizes in the human gut. Recently, the U.S. FDA approved three new
antimicrobial agents against gram-positive bacteria: Tedizolid, Dalbavancin, and
Ceftobiprole. The efficacy of these antibiotics for treatment of C. difficile
infection has not been thoroughly examined. The current study aimed to examine
the in vitro activity of these antibiotics against C. difficile. In addition, to
compare between Dalbavancin and Ceftobiprole to antibiotics from the same class:
Vancomycin and Ceftriaxone, respectively. Methods: Eighty-four C. difficile
isolates were tested for susceptibility to Tedizolid, Dalbavancin, Ceftobiprole,
Vancomycin, and Ceftriaxone by Etest technique in order to determine the minimum
inhibitory concentration (MIC). Results: Upon comparison of the novel antibiotic
agents, Dalbavancin demonstrated the lowest MIC values and ceftobiprole the
highest at MIC50 (0.016, 0.38, and 1.5 MUg/mL, for Dalbavancin, Tedizolid, and
Ceftobiprole, respectively) and MIC90 (0.03, 0.78, and 3.17 MUg/mL,
respectively). Dalbavancin demonstrated significantly lower MIC50 and MIC90
values compared to Vancomycin (0.016 vs. 0.38 and 0.03 vs. 3.5, respectively) (p
< 0.001) and ceftobiprole had significantly lower MIC values compare to
ceftriaxone (1.5 vs. 32 and 3.17 vs. 28.8, respectively) (p < 0.001). Conclusion:
Dalbavancin and Tedizolid may play a role as potential therapeutic agents for
treatment of C. difficile infection. Examination of antibiotic effect on the
intestinal microbiome and clinical trials are needed for more accurate results.
PMID- 29942296
TI - Molecular Diagnosis of Brettanomyces bruxellensis' Sulfur Dioxide Sensitivity
Through Genotype Specific Method.
AB - The yeast species Brettanomyces bruxellensis is associated with important
economic losses due to red wine spoilage. The most common method to prevent
and/or control B. bruxellensis spoilage in winemaking is the addition of sulfur
dioxide into must and wine. However, recently, it was reported that some B.
bruxellensis strains could be tolerant to commonly used doses of SO2. In this
work, B. bruxellensis response to SO2 was assessed in order to explore the
relationship between SO2 tolerance and genotype. We selected 145 isolates
representative of the genetic diversity of the species, and from different
fermentation niches (roughly 70% from grape wine fermentation environment, and
30% from beer, ethanol, tequila, kombucha, etc.). These isolates were grown in
media harboring increasing sulfite concentrations, from 0 to 0.6 mg.L-1 of
molecular SO2. Three behaviors were defined: sensitive strains showed longer lag
phase and slower growth rate and/or lower maximum population size in presence of
increasing concentrations of SO2. Tolerant strains displayed increased lag phase,
but maximal growth rate and maximal population size remained unchanged. Finally,
resistant strains showed no growth variation whatever the SO2 concentrations. 36%
(52/145) of B. bruxellensis isolates were resistant or tolerant to sulfite, and
up to 43% (46/107) when considering only wine isolates. Moreover, most of the
resistant/tolerant strains belonged to two specific genetic groups, allowing the
use of microsatellite genotyping to predict the risk of sulfur dioxide
resistance/tolerance with high reliability (>90%). Such molecular diagnosis could
help the winemakers to adjust antimicrobial techniques and efficient spoilage
prevention with minimal intervention.
PMID- 29942297
TI - Transcriptional Regulation of Cysteine and Methionine Metabolism in Lactobacillus
paracasei FAM18149.
AB - Lactobacillus paracasei is common in the non-starter lactic acid bacteria (LAB)
community of raw milk cheeses. This species can significantly contribute to
flavor formation through amino acid metabolism. In this study, the DNA and RNA of
L. paracasei FAM18149 were sequenced using next-generation sequencing
technologies to reconstruct the metabolism of the sulfur-containing amino acids
cysteine and methionine. Twenty-three genes were found to be involved in cysteine
biosynthesis, the conversion of cysteine to methionine and vice versa, the S
adenosylmethionine recycling pathway, and the transport of sulfur-containing
amino acids. Additionally, six methionine-specific T-boxes and one cysteine
specific T-box were found. Five of these were located upstream of genes encoding
transporter functions. RNA-seq analysis and reverse-transcription quantitative
polymerase reaction assays showed that expression of genes located downstream of
these T-boxes was affected by the absence of either cysteine or methionine.
Remarkably, the cysK2-ctl1-cysE2 operon, which is associated with te methionine
to-cysteine conversion and is upregulated in the absence of cysteine, showed high
read coverage in the 5'-untranslated region and an antisense-RNA in the 3'
untranslated region. This indicates that this operon is regulated by the
combination of cis- and antisense-mediated regulation mechanisms. The results of
this study may help in the selection of L. paracasei strains to control sulfuric
flavor formation in cheese.
PMID- 29942298
TI - Epstein-Barr Virus DNA Enhances Diptericin Expression and Increases Hemocyte
Numbers in Drosophila melanogaster via the Immune Deficiency Pathway.
AB - Infection with the Epstein-Barr virus (EBV) is associated with several
malignancies and autoimmune diseases in humans. The following EBV infection and
establishment of latency, recurrences frequently occur resulting in potential
viral DNA shedding, which may then trigger the activation of immune pathways. We
have previously demonstrated that levels of the pro-inflammatory cytokine IL-17,
which is associated with several autoimmune diseases, are increased in response
to EBV DNA injection in mice. Whether other pro-inflammatory pathways are induced
in EBV DNA pathobiology remains to be investigated. The complexity of mammalian
immune systems presents a challenge to studying differential activities of their
intricate immune pathways in response to a particular immune stimulus. In this
study, we used Drosophila melanogaster to identify innate humoral and cellular
immune pathways that are activated in response to EBV DNA. Injection of wild-type
adult flies with EBV DNA induced the immune deficiency (IMD) pathway resulting in
enhanced expression of the antimicrobial peptide diptericin. Furthermore, EBV DNA
increased the number of hemocytes in flies. Conditional silencing of the IMD
pathway decreased diptericin expression in addition to curbing of hemocyte
proliferation in response to challenge with EBV DNA. Comparatively, upon
injecting mice with EBV DNA, we detected enhanced expression of tumor necrosis
factor-alpha (TNFalpha); this enhancement is rather comparable to IMD pathway
activation in flies. This study hence indicates that D. melanogaster could
possibly be utilized to identify immune mediators that may also play a role in
the response to EBV DNA in higher systems.
PMID- 29942299
TI - Transcriptome Analysis of the Global Response of Pseudomonas fragi NMC25 to
Modified Atmosphere Packaging Stress.
AB - Pseudomonas fragi is usually isolated from chilled meats in relation to their
spoilage, while many studies have shown that the application of modified
atmosphere packaging (MAP) inhibits the spoilage potential of P. fragi. The
effects of MAP on P. fragi NMC25 metabolism were determined in the present study
by exposing this organism to different air conditions and comparing the resulting
transcriptome profiles. We found 559 differentially expressed genes by RNA-seq,
and the results revealed that MAP decreases the expression of genes involved in
the electron transport chain (nuoAB), resulting in an inhibition of aerobic
respiration. Meanwhile, MAP also induced the downregulation of genes responsible
for ATP-binding cassette transporters, flagellar and type I fimbrial proteins,
and DNA replication and repair, which may further influence nutrient uptake,
motility, and growth. In addition, NMC25 cells modified their pathways for energy
production, amino acid synthesis, membrane lipid composition, and other metabolic
patterns to adapt to MAP. These data show that P. fragi NMC25 survives under MAP
but reduces part of its metabolism related to its spoilage ability.
PMID- 29942302
TI - Response: Commentary: Severe Sequelae to Mold-Related Illness as Demonstrated in
Two Finnish Cohorts.
PMID- 29942300
TI - Complement Component 3 Negatively Regulates Antibody Response by Modulation of
Red Blood Cell Antigen.
AB - Red blood cell (RBC) alloimmunization can make it difficult to procure compatible
RBCs for future transfusion, directly leading to increased morbidity and
mortality in transfusion-dependent patients. However, the factors that regulate
RBC alloimmunization remain incompletely understood. As complement has been shown
to serve as a key adjuvant in the development of antibody (Ab) responses against
microbes, we examined the impact of complement on RBC alloimmunization. In
contrast to the impact of complement component 3 (C3) in the development of an
immune response following microbial exposure, transfusion of C3 knockout (C3 KO)
recipients with RBCs expressing KEL (KEL RBCs) actually resulted in an enhanced
anti-KEL Ab response. The impact of C3 appeared to be specific to KEL, as
transfusion of RBCs bearing another model antigen, the chimeric HOD antigen (hen
egg lysozyme, ovalbumin and Duffy), into C3 KO recipients failed to result in a
similar increase in Ab formation. KEL RBCs experienced enhanced C3 deposition and
loss of detectable target antigen over time when compared to HOD RBCs, suggesting
that C3 may inhibit Ab formation by impacting the accessibility of the target KEL
antigen. Loss of detectable KEL on the RBC surface did not reflect antigen
masking by C3, but instead appeared to result from actual removal of the KEL
antigen, as western blot analysis demonstrated complete loss of detectable KEL
protein. Consistent with this, exposure of wild-type B6 or C3 KO recipients to
KEL RBCs with reduced levels of detectable KEL antigen resulted in a
significantly reduced anti-KEL Ab response. These results suggest that C3
possesses a unique ability to actually suppress Ab formation following
transfusion by reducing the availability of the target antigen on the RBC
surface.
PMID- 29942301
TI - Inherited Immunodeficiencies With High Predisposition to Epstein-Barr Virus
Driven Lymphoproliferative Diseases.
AB - Epstein-Barr Virus (EBV) is a gamma-herpes virus that infects 90% of humans
without any symptoms in most cases, but has an oncogenic potential, especially in
immunocompromised individuals. In the past 30 years, several primary
immunodeficiencies (PIDs) associated with a high risk to develop EBV-associated
lymphoproliferative disorders (LPDs), essentially consisting of virus-associated
hemophagocytic syndrome, non-malignant and malignant B-cell LPDs including non
Hodgkin and Hodgkin's types of B lymphomas have been characterized. Among them
are SH2D1A (SAP), XIAP, ITK, MAGT1, CD27, CD70, CTPS1, RASGRP1, and CORO1A
deficiencies. Penetrance of EBV infection ranges from 50 to 100% in those PIDs.
Description of large cohorts and case reports has refined the specific phenotypes
associated with these PIDs helping to the diagnosis. Specific pathways required
for protective immunity to EBV have emerged from studies of these PIDs. SLAM
associated protein-dependent SLAM receptors and MAGT1-dependent NKG2D pathways
are important for T and NK-cell cytotoxicity toward EBV-infected B-cells, while
CD27-CD70 interactions are critical to drive the expansion of EBV-specific T
cells. CTPS1 and RASGRP1 deficiencies further strengthen that T-lymphocyte
expansion is a key step in the immune response to EBV. These pathways appear to
be also important for the anti-tumoral immune surveillance of abnormal B cells.
Monogenic PIDs should be thus considered in case of any EBV-associated LPDs.
PMID- 29942303
TI - The Prognostic Value of Immune Factors in the Tumor Microenvironment of Penile
Squamous Cell Carcinoma.
AB - The host's immune system plays a pivotal role in many tumor types, including
squamous cell carcinomas (SCCs). We aim to identify immunological prognosticators
for lymph node metastases (LNM) and disease-specific survival (DSS) in penile
SCC. For this retrospective observational cohort study, penile SCC patients (n =
213) treated in the Netherlands Cancer Institute, were selected if sufficient
formalin-fixed, paraffin-embedded tumor material was available. Analysis included
previously described high-risk human papilloma virus (hrHPV) status,
immunohistochemical scores for classical and non-classical human leukocyte
antigen (HLA) class I, programmed death ligand-1 (PD-L1) expression, and novel
data on tumor-infiltrating macrophages and cytotoxic an regulatory T-cells.
Clinicopathological characteristics and extended follow-up were also included.
Regression analyses investigated relationships of the immune parameters with LNM
and DSS. In the total cohort, diffuse PD-L1 tumor-cell expression, CD163+
macrophage infiltration, non-classical HLA class I upregulation, and low stromal
CD8+ T-cell infiltration were all associated with LNM. In the multivariable
model, only tumor PD-L1 expression remained a significant predictor for LNM (odds
ratio (OR) 2.8, p = 0.05). hrHPV negativity and diffuse PD-L1 tumor-cell
expression were significantly associated with poor DSS and remained so upon
correction for clinical parameters [hazard ratio (HR) 9.7, p < 0.01 and HR 2.8, p
= 0.03]. The only immune factor with different expression in HPV+ and HPV- tumors
was PD-L1, with higher PD-L1 expression in the latter (p = 0.03). In the HPV-
cohort (n = 158), LNM were associated with diffuse PD-L1 tumor-cell expression,
high intratumoral CD163+ macrophage infiltration, and low number of stromal CD8+
T-cells. The first two parameters were also linked to DSS. In the multivariable
regression model, diffuse PD-L1 expression remained significantly unfavorable for
DSS (HR 5.0, p < 0.01). These results emphasize the complexity of the tumor
microenvironment in penile cancer and point toward several possible immunotherapy
targets. Here described immune factors can aid risk-stratification and should be
evaluated in clinical immunotherapy studies to ultimately lead to patient
tailored treatment.
PMID- 29942304
TI - PU.1 Is Required for the Developmental Progression of Multipotent Progenitors to
Common Lymphoid Progenitors.
AB - The transcription factor PU.1 is required for the development of mature myeloid
and lymphoid cells. Due to this essential role and the importance of PU.1 in
regulating several signature markers of lymphoid progenitors, its precise
function in early lymphopoiesis has been difficult to define. Here, we
demonstrate that PU.1 was required for efficient generation of lymphoid-primed
multipotent progenitors (LMPPs) from hematopoietic stem cells and was essential
for the subsequent formation of common lymphoid progenitors (CLPs). By contrast,
further differentiation into the B-cell lineage was independent of PU.1.
Examination of the transcriptional changes in conditional progenitors revealed
that PU.1 activates lymphoid genes in LMPPs, while repressing genes normally
expressed in neutrophils. These data identify PU.1 as a critical regulator of
lymphoid priming and the transition between LMPPs and CLPs.
PMID- 29942305
TI - Non-Digestible Oligosaccharides Can Suppress Basophil Degranulation in Whole
Blood of Peanut-Allergic Patients.
AB - Background: Dietary non-digestible oligosaccharides (NDOs) have a protective
effect against allergic manifestations in children at risk. Dietary intervention
with NDOs promotes the colonization of beneficial bacteria in the gut and
enhances serum galectin-9 levels in mice and atopic children. Next to this, NDOs
also directly affect immune cells and low amounts may reach the blood. We
investigated whether pre-incubation of whole blood from peanut-allergic patients
with NDOs or galectin-9 can affect basophil degranulation. Methods: Heparinized
blood samples from 15 peanut-allergic adult patients were pre-incubated with a
mixture of short-chain galacto-oligosaccharides and long-chain fructo
oligosaccharides (scGOS/lcFOS), scFOS/lcFOS, or galectin-9 (1 or 5 ug/mL) at 37
degrees C in the presence of IL-3 (0.75 ng/mL). After 2, 6, or 24 h, a basophil
activation test was performed. Expression of FcepsilonRI on basophils, plasma
cytokine, and chemokine concentrations before degranulation were determined after
24 h. Results: Pre-incubation with scGOS/lcFOS, scFOS/lcFOS, or galectin-9
reduced anti-IgE-mediated basophil degranulation. scFOS/lcFOS or 5 ug/mL galectin
9 also decreased peanut-specific basophil degranulation by approximately 20%,
mainly in whole blood from female patients. Inhibitory effects were not related
to diminished FcepsilonRI expression on basophils. Galectin-9 was increased in
plasma after pre-incubation with scGOS/lcFOS, and both NDOs and 5 ug/mL galectin
9 increased MCP-1 production. Conclusion and clinical relevance: The prebiotic
mixture scFOS/lcFOS and galectin-9 can contribute to decreased degranulation of
basophils in vitro in peanut-allergic patients. The exact mechanism needs to be
elucidated, but these NDOs might be useful in reducing allergic symptoms.
PMID- 29942306
TI - Transcriptomic and Quantitative Proteomic Analyses Provide Insights Into the
Phagocytic Killing of Hemocytes in the Oyster Crassostrea gigas.
AB - As invertebrates lack an adaptive immune system, they depend to a large extent on
their innate immune system to recognize and clear invading pathogens. Although
phagocytes play pivotal roles in invertebrate innate immunity, the molecular
mechanisms underlying this killing remain unclear. Cells of this type from the
Pacific oyster Crassostrea gigas were classified efficiently in this study via
fluorescence-activated cell sorting (FACS) based on their phagocytosis of FITC
labeled latex beads. Transcriptomic and quantitative proteomic analyses revealed
a series of differentially expressed genes (DEGs) and proteins present in
phagocytes; of the 352 significantly high expressed proteins identified here
within the phagocyte proteome, 262 corresponding genes were similarly high
expressed in the transcriptome, while 140 of 205 significantly low expressed
proteins within the proteome were transcriptionally low expressed. A pathway
crosstalk network analysis of these significantly high expressed proteins
revealed that phagocytes were highly activated in a number of antimicrobial
related biological processes, including oxidation-reduction and lysosomal
proteolysis processes. A number of DEGs, including oxidase, lysosomal protease,
and immune receptors, were also validated in this study using quantitative PCR,
while seven lysosomal cysteine proteases, referred to as cathepsin Ls, were
significantly high expressed in phagocytes. Results show that the expression
level of cathepsin L protein in phagocytes [mean fluorescence intensity (MFI):
327 +/- 51] was significantly higher (p < 0.01) than that in non-phagocytic
hemocytes (MFI: 83 +/- 26), while the cathepsin L protein was colocalized with
the phagocytosed Vibrio splendidus in oyster hemocytes during this process. The
results of this study collectively suggest that oyster phagocytes possess both
potent oxidative killing and microbial disintegration capacities; these findings
provide important insights into hemocyte phagocytic killing as a component of C.
gigas innate immunity.
PMID- 29942308
TI - Expansion and Antitumor Cytotoxicity of T-Cells Are Augmented by Substrate-Bound
CCL21 and Intercellular Adhesion Molecule 1.
AB - Adoptive immunotherapy is based on ex vivo expansion and stimulation of T-cells,
followed by their transfer into patients. The need for the ex vivo culturing step
provides opportunities for modulating the properties of transferred T-cells,
enhancing their antitumor abilities, and increasing their number. Here, we
present a synthetic immune niche (SIN) that increases the number and antitumor
activity of cytotoxic CD8+ T-cells. We first evaluated the effect of various SIN
compositions that mimic the physiological microenvironment encountered by T-cells
during their activation and expansion in the lymph node. We found that substrates
coated with the chemokine CCL21 together with the adhesion molecule intercellular
adhesion molecule 1 significantly increase the number of ovalbumin-specific
murine CD8+ T-cells activated by antigen-loaded dendritic cells or activation
microbeads. Notably, cells cultured on these substrates also displayed augmented
cytotoxic activity toward ovalbumin-expressing melanoma cells, both in culture
and in vivo. This increase in specific cytotoxic activity was associated with a
major increase in the cellular levels of the killing-mediator granzyme B. Our
results suggest that this SIN may be used for generating T-cells with augmented
cytotoxic function, for use in cancer immunotherapy.
PMID- 29942307
TI - S100A8/A9 in Inflammation.
AB - S100A8 and S100A9 (also known as MRP8 and MRP14, respectively) are Ca2+ binding
proteins belonging to the S100 family. They often exist in the form of
heterodimer, while homodimer exists very little because of the stability.
S100A8/A9 is constitutively expressed in neutrophils and monocytes as a Ca2+
sensor, participating in cytoskeleton rearrangement and arachidonic acid
metabolism. During inflammation, S100A8/A9 is released actively and exerts a
critical role in modulating the inflammatory response by stimulating leukocyte
recruitment and inducing cytokine secretion. S100A8/A9 serves as a candidate
biomarker for diagnosis and follow-up as well as a predictive indicator of
therapeutic responses to inflammation-associated diseases. As blockade of
S100A8/A9 activity using small-molecule inhibitors or antibodies improves
pathological conditions in murine models, the heterodimer has potential as a
therapeutic target. In this review, we provide a comprehensive and detailed
overview of the distribution and biological functions of S100A8/A9 and highlight
its application as a diagnostic and therapeutic target in inflammation-associated
diseases.
PMID- 29942309
TI - Myeloid-Derived Suppressor Cells Hinder the Anti-Cancer Activity of Immune
Checkpoint Inhibitors.
AB - Immune checkpoint inhibitors (ICI) used for cancer immunotherapy were shown to
boost the existing anti-tumor immune response by preventing the inhibition of T
cells by tumor cells. Antibodies targeting two negative immune checkpoint
pathways, namely cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed
cell death protein 1 (PD-1), and programmed cell death-ligand 1 (PD-L1), have
been approved first for patients with melanoma, squamous non-small cell lung
cancer (NSCLC), and renal cell carcinoma. Clinical trials are ongoing to verify
the efficiency of these antibodies for other cancer types and to evaluate
strategies to block other checkpoint molecules. However, a number of patients do
not respond to this treatment possibly due to profound immunosuppression, which
is mediated partly by myeloid-derived suppressor cells (MDSC). This heterogeneous
population of immature myeloid cells can strongly inhibit anti-tumor activities
of T and NK cells and stimulate regulatory T cells (Treg), leading to tumor
progression. Moreover, MDSC can contribute to patient resistance to immune
checkpoint inhibition. Accumulating evidence demonstrates that the frequency and
immunosuppressive function of MDSC in cancer patients can be used as a predictive
marker for therapy response. This review focuses on the role of MDSC in immune
checkpoint inhibition and provides an analysis of combination strategies for MDSC
targeting together with ICI to improve their therapeutic efficiency in cancer
patients.
PMID- 29942310
TI - DN2 Thymocytes Activate a Specific Robust DNA Damage Response to Ionizing
Radiation-Induced DNA Double-Strand Breaks.
AB - For successful bone marrow transplantation (BMT), a preconditioning regime
involving chemo and radiotherapy is used that results in DNA damage to both
hematopoietic and stromal elements. Following radiation exposure, it is well
recognized that a single wave of host-derived thymocytes reconstitutes the
irradiated thymus, with donor-derived thymocytes appearing about 7 days post BMT.
Our previous studies have demonstrated that, in the presence of donor
hematopoietic cells lacking T lineage potential, these host-derived thymocytes
are able to generate a polyclonal cohort of functionally mature peripheral T
cells numerically comprising ~25% of the peripheral T cell pool of euthymic mice.
Importantly, we demonstrated that radioresistant CD44+ CD25+ CD117+ DN2
progenitors were responsible for this thymic auto-reconstitution. Until recently,
the mechanisms underlying the radioresistance of DN2 progenitors were unknown.
Herein, we have used the in vitro "Plastic Thymus" culture system to perform a
detailed investigation of the mechanisms responsible for the high radioresistance
of DN2 cells compared with radiosensitive hematopoietic stem cells. Our results
indicate that several aspects of DN2 biology, such as (i) rapid DNA damage
response (DDR) activation in response to ionizing radiation-induced DNA damage,
(ii) efficient repair of DNA double-strand breaks, and (iii) induction of a
protective G1/S checkpoint contribute to promoting DN2 cell survival post
irradiation. We have previously shown that hypoxia increases the radioresistance
of bone marrow stromal cells in vitro, at least in part by enhancing their DNA
double-strand break (DNA DSB) repair capacity. Since the thymus is also a hypoxic
environment, we investigated the potential effects of hypoxia on the DDR of DN2
thymocytes. Finally, we demonstrate for the first time that de novo DN2
thymocytes are able to rapidly repair DNA DSBs following thymic irradiation in
vivo.
PMID- 29942311
TI - Role of Natural Killer T Cells in the Development of Obesity and Insulin
Resistance: Insights From Recent Progress.
AB - Natural killer T (NKT) cells play important roles in adipose tissue inflammation,
and thus influence the development of diet-induced obesity and insulin
resistance. The interactions between cluster of differentiation (CD)1d and NKT T
cell receptor are thought to be critical in this process, as demonstrated in two
NKT cell-deficient mouse models-systemic CD1d gene knockout (KO) and prototypic
Jalpha18 KO mice. The latter lacks some repertoires besides invariant (i)NKT
cells due to manipulation of the Jalpha18 gene segment; therefore, the role of
iNKT vs. variant NKT cells must be reinterpreted considering the availability of
new Jalpha18 KO mice. NKT cells have varied roles in the development of obesity;
indeed, studies have reported contradictory results depending on the mouse model,
diet, and rearing conditions, all of which could affect the microbiome. In this
mini-review, we discuss these points considering recent findings from our
laboratory and others as well as the role of NKT cells in the development of
obesity and insulin resistance based on data obtained from studies on conditional
CD1d1 KO and new Jalpha18 KO mice generated through gene editing.
PMID- 29942312
TI - Preventive Effect of a Synbiotic Combination of Galacto- and
Fructooligosaccharides Mixture With Bifidobacterium breve M-16V in a Model of
Multiple Rotavirus Infections.
AB - Rotavirus (RV) causes morbidity and mortality among infants worldwide, and there
is evidence that probiotics and prebiotics can have a positive influence against
infective processes such as that due to RV. The aim of this study was to evidence
a preventive role of one prebiotic mixture (of short-chain
galactooligosaccharide/long-chain fructooligosaccharide), the probiotic
Bifidobacterium breve M-16V and the combination of the prebiotic and the
probiotic, as a synbiotic, in a suckling rat double-RV infection model.
Hyperimmune bovine colostrum was used as protection control. The first infection
was induced with RV SA11 and the second one with EDIM. Clinical variables and
immune response were evaluated after both infections. Dietary interventions
ameliorated clinical symptoms after the first infection. The prebiotic and the
synbiotic significantly reduced viral shedding after the first infection, but all
the interventions showed higher viral load than in the RV group after the second
infection. All interventions modulated ex vivo antibody and cytokine production,
gut wash cytokine levels and small intestine gene expression after both
infections. In conclusion, a daily supplement of the products tested in this
preclinical model is highly effective in preventing RV-induced diarrhea but
allowing the boost of the early immune response for a future immune response
against reinfection, suggesting that these components may be potential agents for
modulating RV infection in infants.
PMID- 29942313
TI - Anomalies in T Cell Function Are Associated With Individuals at Risk of
Mycobacterium abscessus Complex Infection.
AB - The increasing global incidence and prevalence of non-tuberculous mycobacteria
(NTM) infection is of growing concern. New evidence of person-to-person
transmission of multidrug-resistant NTM adds to the global concern. The reason
why certain individuals are at risk of NTM infections is unknown. Using high
definition flow cytometry, we studied the immune profiles of two groups that are
at risk of Mycobacterium abscessus complex infection and matched controls. The
first group was cystic fibrosis (CF) patients and the second group was elderly
individuals. CF individuals with active M. abscessus complex infection or a
history of M. abscessus complex infection exhibited a unique surface T cell
phenotype with a marked global deficiency in TNFalpha production during mitogen
stimulation. Importantly, immune-based signatures were identified that appeared
to predict at baseline the subset of CF individuals who were at risk of M.
abscessus complex infection. In contrast, elderly individuals with M. abscessus
complex infection exhibited a separate T cell phenotype underlined by the
presence of exhaustion markers and dysregulation in type 1 cytokine release
during mitogen stimulation. Collectively, these data suggest an association
between T cell signatures and individuals at risk of M. abscessus complex
infection, however, validation of these immune anomalies as robust biomarkers
will require analysis on larger patient cohorts.
PMID- 29942314
TI - Ectonucleotidase-Mediated Suppression of Lupus Autoimmunity and Vascular
Dysfunction.
AB - Objectives: CD39 and CD73 are surface enzymes that jut into the extracellular
space where they mediate the step-wise phosphohydrolysis of the autocrine and
paracrine danger signals ATP and ADP into anti-inflammatory adenosine. Given the
role of vascular and immune cells' "purinergic halo" in maintaining homeostasis,
we hypothesized that the ectonucleotidases CD39 and CD73 might play a protective
role in lupus. Methods: Lupus was modeled by intraperitoneal administration of
pristane to three groups of mice: wild-type (WT), CD39-/-, and CD73-/-. After 36
weeks, autoantibodies, endothelial function, kidney disease, splenocyte
activation/polarization, and neutrophil activation were characterized. Results:
As compared with WT mice, CD39-/- mice developed exaggerated splenomegaly in
response to pristane, while both groups of ectonucleotidase-deficient mice
demonstrated heightened anti-ribonucleoprotein production. The administration of
pristane to WT mice triggered only subtle dysfunction of the arterial
endothelium; however, both CD39-/- and CD73-/- mice demonstrated striking
endothelial dysfunction following induction of lupus, which could be reversed by
superoxide dismutase. Activated B cells and plasma cells were expanded in CD73-/-
mice, while deficiency of either ectonucleotidase led to expansion of TH17 cells.
CD39-/- and CD73-/- mice demonstrated exaggerated neutrophil extracellular trap
release, while CD73-/- mice additionally had higher levels of plasma cell-free
DNA. Conclusion: These data are the first to link ectonucleotidases with lupus
autoimmunity and vascular disease. New therapeutic strategies may harness
purinergic nucleotide dissipation or signaling to limit the damage inflicted upon
organs and blood vessels by lupus.
PMID- 29942315
TI - Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During
Neurotropic Coronavirus-Induced Demyelination.
AB - Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS) characterized by demyelination and axonal loss. Demyelinating
lesions are associated with infiltrating T lymphocytes, bone marrow-derived
macrophages (BMDM), and activated resident microglia. Tissue damage is thought to
be mediated by T cell produced cytokines and chemokines, which activate microglia
and/or BMDM to both strip myelin and produce toxic factors, ultimately damaging
axons and promoting disability. However, the relative contributions of BMDM and
microglia to demyelinating pathology are unclear, as their identification in MS
tissue is difficult due to similar morphology and indistinguishable surface
markers when activated. The CD4 T cell-induced autoimmune murine model of MS,
experimental autoimmune encephalitis (EAE), in which BMDM are essential for
demyelination, has revealed pathogenic and repair-promoting phenotypes associated
with BMDM and microglia, respectively. Using a murine model of demyelination
induced by a gliatropic coronavirus, in which BMDM are redundant for
demyelination, we herein characterize gene expression profiles of BMDM versus
microglia associated with demyelination. While gene expression in CNS
infiltrating BMDM was upregulated early following infection and subsequently
sustained, microglia expressed a more dynamic gene profile with extensive mRNA
upregulation coinciding with peak demyelination after viral control. This delayed
microglia response comprised a highly pro-inflammatory and phagocytic profile.
Furthermore, while BMDM exhibited a mixed phenotype of M1 and M2 markers,
microglia repressed the vast majority of M2-markers. Overall, these data support
a pro-inflammatory and pathogenic role of microglia temporally remote from viral
control, whereas BMDM retained their gene expression profile independent of the
changing environment. As demyelination is caused by multifactorial insults, our
results highlight the plasticity of microglia in responding to distinct
inflammatory settings, which may be relevant for MS pathogenesis.
PMID- 29942316
TI - Identification of DEAD-Box RNA Helicase DDX41 as a Trafficking Protein That
Involves in Multiple Innate Immune Signaling Pathways in a Zebrafish Model.
AB - DDX41 is an important sensor for host recognition of DNA viruses and initiation
of nuclear factor-kappaB (NF-kappaB) and IFN signaling pathways in mammals.
However, its occurrence and functions in other vertebrates remain poorly defined.
Here, a DDX41 ortholog [Danio rerio DDX41 (DrDDX41)] with various conserved
structural features to its mammalian counterparts was identified from a zebrafish
model. This DrDDX41 was found to be a trafficking protein distributed in the
nucleus of resting cells but transported into the cytoplasm under DNA
stimulation. Two nuclear localization signal motifs were localized beside the
coiled-coil domain, whereas one nuclear export signal motif existed in the DEADc
domain. DrDDX41 acts as an initiator for the activation of NF-kappaB and IFN
signaling pathways in a Danio rerio STING (DrSTING)-dependent manner through its
DEADc domain, which is a typical performance of mammalian DDX41. These
observations suggested the conservation of DDX41 proteins throughout the
vertebrate evolution, making zebrafish an alternative model in understanding
DDX41-mediated immunology. With this model system, we found that DrDDX41
contributes to DrSTING-Danio rerio STAT6 (DrSTAT6)-mediated chemokine (Danio
rerio CCL20) production through its DEADc domain. To the best of our knowledge,
this work is the first report showing that DDX41 is an upstream initiator in this
newly identified signaling pathway. The DrDDX41-mediated signaling pathways play
important roles in innate antibacterial immunity because knockdown of either
DrDDX41 or DrSTING/DrSTAT6 significantly reduced the survival of zebrafish under
Aeromonas hydrophilia or Edwardsiella tarda infection. Our findings would enrich
the current knowledge of DDX41-mediated immunology and the evolutionary history
of the DDX41 family.
PMID- 29942317
TI - miR-181a-5p Regulates TNF-alpha and miR-21a-5p Influences Gualynate-Binding
Protein 5 and IL-10 Expression in Macrophages Affecting Host Control of Brucella
abortus Infection.
AB - Brucella abortus is a Gram-negative intracellular bacterium that causes a
worldwide zoonosis termed brucellosis, which is characterized as a debilitating
infection with serious clinical manifestations leading to severe complications.
In spite of great advances in studies involving host-B. abortus interactions,
there are many gaps related to B. abortus modulation of the host immune response
through regulatory mechanisms. Here, we deep sequenced small RNAs from bone
marrow-derived macrophages infected with B. abortus, identifying 69 microRNAs
(miRNAs) that were differentially expressed during infection. We further
validated the expression of four upregulated and five downregulated miRNAs during
infection in vitro that displayed the same profile in spleens from infected mice
at 1, 3, or 6 days post-infection. Among these miRNAs, mmu-miR-181a-5p
(upregulated) or mmu-miR-21a-5p (downregulated) were selected for further
analysis. First, we determined that changes in the expression of both miRNAs
induced by infection were dependent on the adaptor molecule MyD88. Furthermore,
evaluating putative targets of mmu-miR-181a-5p, we demonstrated this miRNA
negatively regulates TNF-alpha expression following Brucella infection. By
contrast, miR-21a-5p targets included a negative regulator of IL-10, programmed
cell death protein 4, and several guanylate-binding proteins (GBPs). As a result,
during infection, miR-21a-5p led to upregulation of IL-10 expression and
downregulation of GBP5 in macrophages infected with Brucella. Since GBP5 and IL
10 are important molecules involved in host control of Brucella infection, we
decided to investigate the role of mmu-miR-21a-5p in bacterial replication in
macrophages. We observed that treating macrophages with a mmu-miR-21a-5p mimic
enhanced bacterial growth, whereas transfection of its inhibitor reduced Brucella
load in macrophages. Taken together, the results indicate that downregulation of
mmu-miR-21a-5p induced by infection increases GBP5 levels and decreases IL-10
expression thus contributing to bacterial control in host cells.
PMID- 29942318
TI - Mucosal-Associated Invariant T Cells in Autoimmune Diseases.
AB - Mucosal-associated invariant T (MAIT) cells are innate T cells restricted by MHC
related molecule 1 (MR1). MAIT cells express semi-invariant T-cell receptors
TRAV1-2-TRAJ33/12/20 in humans and TRAV1-TRAJ33 in mice. MAIT cells recognize
vitamin B2 biosynthesis derivatives presented by MR1. Similar to other innate
lymphocytes, MAIT cells are also activated by cytokines in the absence of
exogenous antigens. MAIT cells have the capacity to produce cytokines, such as
IFNgamma, TNFalpha, and IL-17, and cytotoxic proteins, including perforin and
granzyme B. MAIT cells were originally named after their preferential location in
the mucosal tissue of the gut, but they are also abundant in other peripheral
organs, including the liver and lungs. In humans, the frequency of MAIT cells is
high in peripheral blood, and these cells constitute approximately 5% of
circulating CD3+ cells. Their abundance in tissues and rapid activation following
stimulation have led to great interest in their function in various types of
immune diseases. In this review, first, we will briefly introduce key information
of MAIT cell biology required for better understating their roles in immune
responses, and then describe how MAIT cells are associated with autoimmune and
other immune diseases in humans. Moreover, we will discuss their functions based
on information from animal models of autoimmune and immunological diseases.
PMID- 29942319
TI - Role of Glial Immunity in Lifespan Determination: A Drosophila Perspective.
AB - Increasing body of evidence indicates that proper glial function plays an
important role in neuroprotection and in organismal physiology throughout
lifespan. Work done in the model organism Drosophila melanogaster has revealed
important aspects of glial cell biology in the contexts of longevity and
neurodegeneration. In this mini review, we summarize recent findings from work
done in the fruit fly Drosophila about the role of glia in maintaining a healthy
status during animal's life and discuss the involvement of glial innate immune
pathways in lifespan and neurodegeneration. Overactive nuclear factor kappa B (NF
kappaB) pathways and defective phagocytosis appear to be major contributors to
lifespan shortening and neuropathology. Glial NF-kappaB silencing on the other
hand, extends lifespan possibly through an immune-neuroendocrine axis. Given the
evolutionary conservation of NF-kappaB innate immune signaling and of macrophage
ontogeny across fruit flies, rodents, and humans, the above observations in glia
could potentially support efforts for therapeutic interventions targeting to
ameliorate age-related pathologies.
PMID- 29942320
TI - Across Multiple Species, Phytochemical Diversity and Herbivore Diet Breadth Have
Cascading Effects on Herbivore Immunity and Parasitism in a Tropical Model
System.
AB - Terrestrial tri-trophic interactions account for a large part of biodiversity,
with approximately 75% represented in plant-insect-parasitoid interactions.
Herbivore diet breadth is an important factor mediating these tri-trophic
interactions, as specialisation can influence how herbivore fitness is affected
by plant traits. We investigated how phytochemistry, herbivore immunity, and
herbivore diet breadth mediate plant-caterpillar-parasitoid interactions on the
tropical plant genus Piper (Piperaceae) at La Selva Biological station in Costa
Rica and at Yanayacu Biological Station in Ecuador. We collected larval stages of
one Piper generalist species, Quadrus cerealis, (Lepidoptera: Hesperiidae) and 4
specialist species in the genus Eois (Lepidoptera: Geometridae) from 15 different
species of Piper, reared them on host leaf material, and assayed phenoloxidase
activity as a measure of potential larval immunity. We combined these data with
parasitism and caterpillar species diet breadth calculated from a 19-year
database, as well as established values of phytochemical diversity calculated for
each plant species, in order to test specific hypotheses about how these
variables are related. We found that phytochemical diversity was an important
predictor for herbivore immunity, herbivore parasitism, and diet breadth for
specialist caterpillars, but that the direction and magnitude of these
relationships differed between sites. In Costa Rica, specialist herbivore immune
function was negatively associated with the phytochemical diversity of the Piper
host plants, and rates of parasitism decreased with higher immune function. The
same was true for Ecuador with the exception that there was a positive
association between immune function and phytochemical diversity. Furthermore,
phytochemical diversity did not affect herbivore immunity and parasitism for the
more generalised herbivore. Results also indicated that small differences in
herbivore diet breadth are an important factor mediating herbivore immunity and
parasitism success for Eois at both sites. These patterns contribute to a growing
body of literature that demonstrate strong cascading effects of phytochemistry on
higher trophic levels that are dependent on herbivore specialisation and that can
vary in space and time. Investigating the interface between herbivore immunity,
plant chemical defence, and parasitoids is an important facet of tri-trophic
interactions that can help to explain the enormous amount of biodiversity found
in the tropics.
PMID- 29942323
TI - Editorial: Optical Approaches to Capture Plant Dynamics in Time, Space, and
Across Scales.
PMID- 29942322
TI - Genome-Wide Identification of TCP Family Transcription Factors in Medicago
truncatula Reveals Significant Roles of miR319-Targeted TCPs in Nodule
Development.
AB - TCP proteins, the plant-specific transcription factors, are involved in the
regulation of multiple aspects of plant development among different species, such
as leaf development, branching, and flower symmetry. However, thus far, the roles
of TCPs in legume, especially in nodulation are still not clear. In this study, a
genome-wide analysis of TCP genes was carried out to discover their evolution and
function in Medicago truncatula. In total, 21 MtTCPs were identified and
classified into class I and class II, and the class II MtTCPs were further
divided into two subclasses, CIN and CYC/TB1. The expression profiles of MtTCPs
are dramatically different. The universal expression of class I MtTCPs was
detected in all organs. However, the MtTCPs in CIN subclass were highly expressed
in leaf and most of the members in CYC/TB1 subclass were highly expressed in
flower. Such organ-specific expression patterns of MtTCPs suggest their different
roles in plant development. In addition, most MtTCPs were down-regulated during
the nodule development, except for the putative MtmiR319 targets, MtTCP3, MtTCP4,
and MtTCP10A. Overexpression of MtmiR319A significantly reduced the expression
level of MtTCP3/4/10A/10B and resulted in the decreased nodule number, indicating
the important roles of MtmiR319-targeted MtTCPs in nodulation. Taken together,
this study systematically analyzes the MtTCP gene family at a genome-wide level
and their possible functions in nodulation, which lay the basis for further
explorations of MtmiR319/MtTCPs module in association with nodule development in
M. truncatula.
PMID- 29942324
TI - Microtensile Bond Strength Between Zirconia Core and Veneering Porcelain After
Different Surface Treatments.
AB - Objectives: The long-term clinical success of all-ceramic restorations requires
sufficient bond strength between the veneering ceramic and substructure. The
present study compared the effects of three methods of surface treatment on the
microtensile bond strength of the veneering porcelain to zirconia. Materials and
Methods: Twelve zirconia blocks were randomly divided into four groups of
aluminum oxide (Al2O3) air abrasion, carbon dioxide (CO2) laser irradiation,
erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation, and control
samples (no surface treatment). After surface treatment, the zirconia blocks were
veneered with porcelain. To assess the surface topographies, four surface-treated
specimens were left uncoated. Microtensile bond strength was tested in each group
and was statistically analyzed by one-way ANOVA and post-hoc Tukey's test.
Surface topographies were examined by using scanning electron microscopy (SEM).
Results: The highest and lowest microtensile bond strength values were recorded
in the Al2O3 (43.6+/-10.0 MPa) and control groups (34.7+/-8.2 MPa, P<0.05). The
bond strengths in the CO2- and Er:YAG-irradiated groups were equal to 40.4+/-6.5
MPa and 38.2+/-7.5 MPa, respectively. The majority of the failures (mean=92.44%)
were of cohesive nature located in the veneer, followed by mixed fractures
(mean=7.6%). The milling marks of the computer-aided design/computer-aided
manufacturing (CAD/CAM) machine were apparent in the control samples, while
desert-like micro-cracks were observed on the surfaces treated with CO2 and
Er:YAG lasers. Al2O3 air abrasion produced the roughest topography. Conclusions:
Al2O3 air abrasion resulted in a higher microtensile bond strength compared to
CO2 or Er:YAG laser irradiation. Cohesive failure mode was predominant. No pure
adhesive failures were observed.
PMID- 29942321
TI - Abiotic Stress Signaling in Wheat - An Inclusive Overview of Hormonal
Interactions During Abiotic Stress Responses in Wheat.
AB - Rapid global warming directly impacts agricultural productivity and poses a major
challenge to the present-day agriculture. Recent climate change models predict
severe losses in crop production worldwide due to the changing environment, and
in wheat, this can be as large as 42 Mt/ degrees C rise in temperature. Although
wheat occupies the largest total harvested area (38.8%) among the cereals
including rice and maize, its total productivity remains the lowest. The major
production losses in wheat are caused more by abiotic stresses such as drought,
salinity, and high temperature than by biotic insults. Thus, understanding the
effects of these stresses becomes indispensable for wheat improvement programs
which have depended mainly on the genetic variations present in the wheat genome
through conventional breeding. Notably, recent biotechnological breakthroughs in
the understanding of gene functions and access to whole genome sequences have
opened new avenues for crop improvement. Despite the availability of such
resources in wheat, progress is still limited to the understanding of the stress
signaling mechanisms using model plants such as Arabidopsis, rice and
Brachypodium and not directly using wheat as the model organism. This review
presents an inclusive overview of the phenotypic and physiological changes in
wheat due to various abiotic stresses followed by the current state of knowledge
on the identified mechanisms of perception and signal transduction in wheat.
Specifically, this review provides an in-depth analysis of different hormonal
interactions and signaling observed during abiotic stress signaling in wheat.
PMID- 29942325
TI - Comparison of the Efficacy of Topical Triamcinolone in Orabase and Curcumin in
Orabase in Oral Graft-Versus-Host Disease.
AB - Objectives: Graft-versus-host disease (GVHD) is among the most frequent
complications of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD
has several clinical manifestations in the oral cavity, including painful
desquamative erythema, ulcerative mucosal lesions, and lichenoid lesions. The
patients presenting with oral GVHD complain of oral sensitivity, pain, dysgeusia,
and xerostomia. The treatment of oral GVHD includes a proper systemic therapy
combined with a good oral hygiene and the use of local and topical steroids.
Corticosteroids and immunosuppressants are used for the treatment of chronic oral
GVHD; however, they are associated with different complications. Evidence shows
that curcumin has anti-inflammatory and antioxidative properties. The treatment
of lichen planus and oral mucositis with curcumin has been successful. This study
aimed to compare the efficacy of topical curcumin in Orabase and triamcinolone in
Orabase in the patients affected by oral GVHD. Materials and Methods: Twenty-six
patients presenting with oral GVHD were randomly divided into two groups of 13
using block randomization. The control group used triamcinolone in Orabase, and
the case group received curcumin in Orabase. Results: The two groups were not
significantly different in terms of the alleviated severity of the lesions at the
end of the treatment (P=0.052). The comparison of the pain score via the visual
analog scale (VAS) at the onset of the treatment and at days 14 and 28
(completion of the treatment) showed no significant difference between the two
groups (P>0.05). Conclusions: Curcumin has comparable efficacy to that of
triamcinolone and may be prescribed for the patients presenting with oral GVHD.
PMID- 29942326
TI - Fracture Resistance of Zirconia Restorations with a Modified Framework Design.
AB - Objectives: Chipping is one of the concerns related to zirconia crowns. The
reasons of chipping have not been completely understood. This in-vitro study
aimed to assess the effect of coping design on the fracture resistance of all
ceramic single crowns with zirconia frameworks. Materials and Methods: Two types
of zirconia copings were designed (n=12): (1) a standard coping (SC) with a 0.5mm
uniform thickness and (2) a modified coping (MC) consisted of a lingual margin of
1mm thickness and 2mm height connected to a proximal strut of 4mm height and a
0.3mm-wide facial collar. After veneer porcelain firing, the crowns were cemented
to metal dies. Afterwards, a static vertical load was applied until failure. The
modes of failure were determined. Data were calculated and statistically analyzed
by independent samples T-test. P<0.05 was considered statistically significant.
Results: The mean and standard deviation (SD) of the final fracture resistance
equaled to 3519.42+/-1154.96 N and 3570.01+/-1224.33 N in SC and MC groups,
respectively; the difference was not statistically significant (P=0.9). Also, the
mean and SD of the initial fracture resistance equaled to 3345.34+/-1190.93 N and
3471.52+/-1228.93 N in SC and MC groups, respectively (P=0.8). Most of the
specimens in both groups showed the mixed failure mode. Conclusions: Based on the
results, the modified core design may not significantly improve the fracture
resistance.
PMID- 29942327
TI - Effect of Dental Implant Metal Artifacts on Accuracy of Linear Measurements by
Two Cone-Beam Computed Tomography Systems Before and After Crown Restoration.
AB - Objectives: The aim of this study was to determine the impact of fixture location
and crown restoration on the accuracy of linear measurements by two cone-beam
computed tomography (CBCT) systems. Materials and Methods: Six dental implants
were inserted in a dry human mandible in two stages. CBCT images were obtained in
each stage by Alphard VEGA 3030 and Promax 3D Max systems. Imaging procedures
were repeated after metallic crown placement. Two observers measured the alveolar
height and width using five radiopaque markers. Values were compared to the same
measurements made on initial images (prior to implant insertion) using t-test.
The linear regression test was used to evaluate the effect of implant location on
the accuracy of linear measurements. Results: The impact of fixture and fixture
crown combination on the accuracy of linear measurements of height (t = -5.2,
P=0.0001 and t=-5.98, P<0.0001, respectively) and width (t=-3.42, P=0.004 and t=
2.7, P=0.015, respectively) was significantly underestimated. Metal crowns had no
significant effect on measurements of bone height and width (t=-1.38, P=0.19 and
t=0, P=1.00, respectively). Although both systems showed some underestimations,
Promax 3D Max underestimated bone width significantly more than the other system
(Alphard VEGA 3030=- 0.51mm and Promax 3D Max=-0.80). Regarding implant location,
the measurements in the canine sites were found to be more accurate than the
region between adjacent implants. Conclusions: CBCT is an accurate and
reproducible system for dental implant follow-up examinations. Metal artifacts
can lead to underestimation of measurements. However, this was not statistically
significant in our study.
PMID- 29942328
TI - Adherence of Streptococcus Mutans to Microhybrid and Nanohybrid Resin Composites
and Dental Amalgam: An In Vitro Study.
AB - Objectives: Streptococcus mutans (S. mutans) is a cariogenic microorganism. The
restorative materials which harbor a biofilm with high levels of S. mutans can
accelerate the occurrence of dental caries. The purpose of this study was to
evaluate the influence of different restorative materials on S. mutans
colonization in a simple in-vitro biofilm formation model. Materials and Methods:
Thirteen discs of each material (nanohybrid resin composite, microhybrid resin
composite, and amalgam) were prepared, polished, and sterilized in a gamma
radiation chamber. The saliva-free specimens were exposed to the S. mutans
bacterial suspension (0.5 McFarland) and were incubated for 4 hours. Afterwards,
the specimens were rinsed and sonicated in normal saline. 10MUl of the obtained
suspension was cultured in a sterile blood agar medium. After 24 hours, the
number of colony forming units (CFU) of S. mutans was counted. A sterility test
control was considered for each group of materials. The data were analyzed by one
way ANOVA at 5% significance level. Results: The means and standard deviations of
the logarithmic values of the colonies on the surfaces of amalgam, microhybrid,
and nanohybrid resin composites were equal to 3.76+/-0.64, 3.91+/-0.52 and 3.34+/
0.74, respectively. Conclusions: There were no significant differences between
the restorative materials in terms of S. mutans adhesion rate. The evaluated
resin composites showed comparable numbers of CFUs, which could imply the
importance of the polishing procedures.
PMID- 29942329
TI - Effect of Flapless Immediate Implantation and Filling the Buccal Gap with
Xenograft Material on the Buccal Bone Level: A Randomized Clinical Trial.
AB - Objectives: Following tooth extraction, soft and hard tissue alterations occur;
Different factors can affect this process. The objective of this study was to
determine the effect of gap filling on buccal alveolar crestal bone level after
immediate implant placement after 4- to 6-month observation period. Materials and
Methods: This randomized clinical trial was performed on 20 patients (mean age of
38.8 years) requiring tooth extraction in a total of 27 areas in the anterior
maxilla. The treatment strategy was as follows: atraumatic flapless tooth
extraction, implant placement, insertion of a graft (test group) or no material
(control group) between the implant and the socket wall, connection healing
abutment placement and suturing the area. Clinical and cone beam computed
tomographic examinations were performed before implant placement (baseline), 24
hours after surgery and 4-6 months (T2) after implant placement, to assess the
buccal plate height (BH) and implant complications. Results: After 4 months of
healing, a reduction in different bone measurements was noticed in the two
groups. No statistically significant differences were assessed in bone height
measurements between the test and control groups at different time points. The
study demonstrated that immediate implantation resulted in 1.30 and 1.66 mm
reduction in buccal bone plate in the test and control groups, respectively.
Conclusions: The study demonstrated that immediate implantation in the extraction
socket together with xenograft failed to prevent bone resorption.
PMID- 29942330
TI - Application of Multilevel Models in Dentistry.
AB - Multilevel analysis which was primarily introduced to deal with hierarchical data
was later applied extensively for research in other fields of science and not
only for nested data, but also for repeated measurements or clustered trials.
This method of statistical analysis was applied in dental studies in the 1991 for
the first time but despite its value for data analysis in dental studies, its
application for dental studies remains limited until now. This manuscript reviews
the applications of this method in dental studies.
PMID- 29942331
TI - Effect of Treatment of Obstructive Sleep Apnea by Uvulopalatoplasty on Seizure
Outcomes: A Case Report.
AB - It is estimated that one-third of the people with refractory epilepsy suffer from
obstructive sleep apnea (OSA). In a patient presenting with OSA symptoms and
epilepsy, removing a portion of the soft palate (uvulopalatoplasty) can be
considered the treatment of choice for eliminating the OSA and decreasing the
seizures. Here, we report the results of our surgical approach by which the
patient's problems completely resolved, and we observed no symptoms of OSA or
epilepsy after the surgery. After 10 years of follow-up, the patient is seizure
free and does not need any antiepileptic drugs.
PMID- 29942332
TI - The effect of salusin-beta on expression of pro- and anti-inflammatory cytokines
in human umbilical vein endothelial cells (HUVECs).
AB - BACKGROUND: Atherosclerosis is one of the predominant causes of cardiovascular
disease (CVD). Several studies indicated the significant pathophysiological role
of salusin-beta in atherosclerosis. Cytokines are involved in all stages of
atherosclerosis. Therefore, we aimed to assess the effect of salusin-beta on
interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18) (as
inflammatory cytokines) and interleukin 1Ra (IL-1Ra) (as anti-inflammatory
cytokines) levels in human umbilical vein endothelial cells (HUVECs). METHODS:
The HUVECs were cultured in HUVEC completed medium and treated with different
doses of salusin-beta for 6 and 12 hours. For the investigation of nuclear factor
kbeta (NF-kbeta) signaling pathway involvement, cells were treated in the
presence or absence of Bay 11-7082 (as NF-kbeta inhibitor). The mRNA expression
and protein level of cytokines were measured by a real-time polymerase chain
reaction (PCR) system and enzyme-linked immunosorbent assay (ELISA) method,
respectively. RESULTS: Salusin-beta increased mRNA expression and protein level
of IL-6, IL-8 and IL-18. This protein decreased mRNA and protein level of IL-1Ra
in HUVECs. NF-kbeta signaling pathway was involved in the up-regulatory effect of
salusin-beta on mRNA expression of pro-inflammatory cytokines. The down
regulatory effect of salusin-beta on IL-1Ra expression could not be influenced by
Bay 11-7082 pre-treatment. CONCLUSION: It seems that salusin-beta may participate
in a cascade pathway in vascular inflammation. Our findings suggested that
salusin-beta has potential use as a therapeutic target for atherosclerosis.
PMID- 29942333
TI - The relationship between serum vitamin D levels and ankle-brachial index in
patients with metabolic syndrome.
AB - BACKGROUND: Vitamin D deficiency is a prevalent condition in Iran and previous
studies have shown that a low level of serum vitamin D is related to low ankle
brachial index (ABI). In the present study, the relationship of the serum level
of vitamin D with ABI, as an index for atherosclerosis of peripheral arteries,
was evaluated. METHODS: In this cross-sectional study, data on 91 patients with
metabolic syndrome (Mets) from the Isfahan Cohort Study (ICS) were analyzed in
order to evaluate the association between serum 25(OH) vitamin D level and ABI.
The participants were divided into two groups; group A with desirable serum
vitamin D level and group B with abnormal serum vitamin D level. ABI was measured
and compared between these groups. RESULTS: A crude and adjusted model showed no
association between vitamin D level and ABI in patients with MetS. CONCLUSION: It
can be concluded that serum vitamin D level could not affect ABI in patients with
MetS.
PMID- 29942334
TI - Prediction of the ischemic origin of functional mitral regurgitation in patients
with systolic heart failure through posterior mitral leaflet angle.
AB - BACKGROUND: Differentiating ischemic from non-ischemic functional mitral
regurgitationy (FMR) in patients with cardiomyopathy is important in terms of the
therapeutic decision-making and prognosis, but might be clinically challenging.
In this study, the deformation of mitral valve (MV) indices in the prediction of
the etiology of FMR was assessed using 2D transthoracic and tissue Doppler
echocardiography. METHODS: This case-control study was conducted from April 2015
to January 2016 in Imam Reza Hospital in Mashhad, Iran. The participants
consisted of 40 patients with ischemic cardiomyopathy (ICM) and 22 with non
ischemic dilated cardiomyopathy (DCM) who referred to the heart failure clinic.
Transthoracic echocardiography was performed using the conventional 2D and tissue
Doppler imaging (TDI). MV tenting area (TA), coaptation distance (CD), anterior
and posterior mitral leaflet angles (AMLA and PMLA), and regional systolic
myocardial velocity (Sm) were measured. RESULTS: There were no significant
differences in echocardiographic indices between the two groups, besides Sm and
PMLA which were significantly lower and higher, respectively, in ICM subjects in
comparison with DCM patients (P = 0.002). PMLA >= 40 degrees and Sm <= 4
cm/second have a relatively high value for discriminating the ischemic from non
ischemic origin of functional MR in subjects with systolic heart failure
(sensitivity: 80.0% and 70.0%, specificity: 73.0% and 77.3%; P = 0.001 and P <
0.001; respectively). Multivariable logistic regression identified PMLA and
anterior Sm as major determinants for ischemic MR {Odds ratio (OR) [95%
confidence interval (CI)] = 0.89 (0.82-0.96), P = 0.003, OR (95% CI) = 0.29 (0.14
0.60), P = 0.001, respectively}. CONCLUSION: The present study showed that PMLA
and Sm had an independent significant association with the mechanism of FMR.
These findings are suggestive of the predictive role of mitral deformation
echocardiographic indices in the determination of the etiology of FMR in systolic
heart failure.
PMID- 29942335
TI - Comparison of the effect of the Dietary Approaches to Stop Hypertension diet with
usual dietary advice on expression of peroxisome proliferators-activated receptor
gamma gene in women: A randomized controlled clinical trial.
AB - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) which
controls body weight, glucose homeostasis, and adipocyte differentiation is a
valuable candidate gene for insulin resistance (IR). The present study aimed to
compare the effects of the Dietary Approaches to Stop Hypertension (DASH) diet
and usual dietary advice (UDA) on PPAR-gamma gene expression in women at risk for
cardiovascular disease (CVD). METHODS: This randomized controlled trial was
performed on 44 women aged 20-50 years at risk for CVD (BMI > 25 kg/m2 and low
physical activity). Participants were randomly assigned to the UDA (n = 22) or
DASH (n = 22) diets for 12 weeks. The DASH diet was rich in fruits, vegetables,
whole grains and low-fat dairy products and low in saturated fat, total fat,
cholesterol, refined grains and sweets, with a total of 2400 mg/day sodium. The
UDA diet was a regular diet with healthy dietary advice. Anthropometric indices
and PPAR-gamma gene expression were measured and compared between the two groups
at the end of the study. RESULTS: After the intervention, body mass index (BMI)
and waist circumference (WC) significantly decreased in the DASH group (P <
0.050) but the results showed no significant differences between the two groups.
At the end of the trial, PPAR-gamma gene expression was significantly different
between the UDA and the DASH diet groups (P = 0.040) and this difference remained
significant after adjustment for BMI, and physical activity (P = 0.030).
CONCLUSION: The result of the study showed that the DASH diet significantly
decreased the expression of PPAR-gamma. This finding was unexpected and future
studies on the current topic are therefore recommended.
PMID- 29942336
TI - Epicardial fat thickness and severity of coronary heart disease in patients with
diabetes mellitus type II.
AB - BACKGROUND: Clinical imaging studies have demonstrated a strong direct
correlation between epicardial fat and abdominal visceral adiposity. There are
several studies about positive correlation of epicardial fat and atherosclerotic
coronary disease in general population. This study aimed to evaluate the
association of epicardial fat thickness with atherosclerotic coronary disease in
patients with diabetes mellitus type II. METHODS: This cross-sectional
observational study involved 80 patients with diabetes mellitus type II. The
patients were chosen using simple sampling method from patients with diabetes
mellitus who were referred for angiography because of suspected coronary artery
disease. The severity of coronary atherosclerotic lesions was evaluated using
modified Gensini scoring system. Epicardial fat thickness was measured by
transthoracic echocardiography within 90 days after coronary angiography.
Multiple linear regression method was used to evaluate the association between
mean epicardial fat thickness and Gensini score. RESULTS: After adjustment for
the effects of body mass index (BMI), age, angina, and sex, there was a
significant association between Gensini score and epicardial fat thickness (beta
= 0.825; P < 0.001). Patients with higher blood pressure and higher body mass
index also had a higher Gensini score (P < 0.010). CONCLUSION: In patients with
diabetes mellitus type II, there is a positive association between epicardial fat
thickness and severity of coronary artery disease. So, by echocardiography
evaluation of epicardial fat thickness, we could have an estimation of the
severity of coronary arteries diseases before using more invasive techniques.
PMID- 29942337
TI - Unusual management of parturient patient with severe bicuspid aortic valve
stenosis and congestive heart failure.
AB - BACKGROUND: Critical aortic stenosis (AS) is an unusual cardiac pathology in
pregnancy, but has significant impact on the fetal and maternal outcomes of
pregnancy. Pregnant patients with aortic stenosis and heart failure represent a
major challenge for the heart team and anesthesiologist who should balance the
risks and benefits of different treatment strategies and their effects on the
mother and fetus. CASE REPORT: We present a 26-year-old parturient who underwent
cesarean section at 30 weeks of gestation under general anesthesia in the
presence of cardiac surgical team followed by deferred aortic valve replacement
after two weeks. CONCLUSION: This report describes the importance of
multidisciplinary preoperative evaluation, and careful surgical and anesthetic
planning to avoid the deterioration of perioperative cardiac condition in such
patients.
PMID- 29942338
TI - A rare case of spontaneous and simultaneous multivessel coronary artery spasm
leading to multisite myocardial infarction and ventricular fibrillation.
AB - BACKGROUND: Coronary artery spasm (CAS) can result in life-threatening arrhythmia
and sudden cardiac death. Although this disorder has been known for a long time,
little is known about it, and its mechanisms have been not identified yet. CASE
REPORT: We describe a 52-year-old woman with no significant cardiovascular risk
factors who experienced several episodes of spontaneous and coincident
multivessel coronary artery spasm, which led to myocardial infarction as well as
malignant arrhythmias. Coronary angiography revealed severe migratory narrowing
in the left anterior descending artery and right coronary artery. CONCLUSION:
Simultaneous multivessel coronary artery spasm develop multisite myocardial
infarction (MI), and malignant arrhythmias could occur even in the absence of
significant stenosis and triggering factors, which would lead to an increased
risk of life-threatening cardiac events.
PMID- 29942339
TI - Off-center cardiac rehabilitation focused on extended emotional relationship and
common health gains.
PMID- 29942341
TI - Chewing khat and risky sexual behavior among residents of Bahir Dar City
administration, Northwest Ethiopia.
AB - Introduction: Khat is a well-known natural stimulant and is widely used in
Ethiopia, particularly in Bahir Dar city. Khat chewing is linked with risky
sexual behaviors. Objective: The study was aimed to determine the prevalence of
chewing khat and its relation with risky sexual behaviors among residents of
Bahir Dar City administration, Northwest Ethiopia. Methods: A community based
cross-sectional study was conducted from January to February, 2016. The data were
collected using an interviewer administered structured questionnaire. Logistic
regression analysis was applied to assess association between dependent and
explanatory variables. Results: The proportion of lifetime and current chewing
khat among the study participants were 25.7 and 19.5%, respectively. Males (AOR
5.0; 95% CI 3.0-8.2) than females, merchants (AOR 4.9; 95% CI 2.6-9.3) than
government employees, and those with average monthly income of >= 3001 Ethiopian
birr (AOR 2.4; 95% CI 1.2-4.8) than <= 1000 had an increased current chewing khat
prevalence. Having lifetime history of chewing khat was significantly associated
with ever had sexual intercourse, having extra sexual partners, watching
pornographic film and self-reported sexually transmitted infections. Conclusion:
Chewing khat is associated with increment of having risky sexual behaviors and
self-reported sexually transmitted infections. Harm reduction measures are needed
to prevent the community from engaging in khat use and risky sexual behaviors.
PMID- 29942340
TI - Metformin in the management of diabetes during pregnancy and lactation.
AB - This review explores the current place of metformin in the management of
gestational diabetes (GDM) and type 2 diabetes during pregnancy and lactation.
The rationale and basic pharmacology of metformin usage in pregnancy is discussed
along with the evidence from observational and randomized controlled trials in
women with GDM or overt diabetes. There seems to be adequate evidence of efficacy
and short-term safety of metformin in relation to maternal and neonatal outcomes
in GDM, with possible benefits related to lower maternal weight gain and lower
risk of neonatal hypoglycemia and macrosomia. Additionally, metformin offers the
advantages of oral administration, convenience, less cost and greater
acceptability. Metformin may, therefore, be considered in milder forms of GDM
where glycemic goals are not attained by lifestyle modification. However, failure
rate is likely to be higher in those with an earlier diagnosis of GDM, higher
blood glucose, higher body mass index (BMI) or previous history of GDM, and
insulin remains the cornerstone of pharmacological treatment in such cases. The
use of metformin in type 2 diabetes has been assessed in observational and small
randomized trials. Metformin monotherapy in women with overt diabetes is highly
unlikely to achieve glycemic targets. Hence, the use should be restricted as
adjunct to insulin and may be considered in women with high insulin dose
requirements or rapid weight gain. There is clearly a need for more clinical
trials to assess the effect of combined insulin plus metformin therapy in
pregnancy with type 2 diabetes. Additionally, there is a paucity of data on long
term effects in offspring exposed to metformin in utero. It is imperative to
further explore its impact on offspring as metformin has significant
transplacental transfer and has the potential to impact the programming of the
epigenome. Therefore, caution must be exercised when prescribing metformin in
pregnant women. More research is clearly needed before metformin can be
considered as standard of care in the management of diabetes during pregnancy.
PMID- 29942342
TI - Determinants of depression among people with epilepsy in Central Ethiopia.
AB - Background: Depression is the most frequently and highly occurring mental
disorders in epilepsy patients. When depression is comorbid with epilepsy, it
leads to low employment and poor quality of life. Thus, the aim of this study was
to assess the prevalence and associated factors of depression among people living
with epilepsy in Central Ethiopia. Methods: Institution-based cross-sectional
study was conducted from April to May 2015 at Amanuel Mental Specialized and
TikurAnbesa Hospitals, Addis Ababa, Ethiopia. Samples of 422 epilepsy patients
were selected, and data on depression were collected using validated
questionnaire using face-to-face interview technique. Logistic regression
analysis was performed to assess predictors of depression. Results: The study
indicated that the prevalence of depression among people with epilepsy was 43.8%.
Factors associated with depression were being female (AOR 2.48; 95% CI,
1.61.3.81), being single (AOR 2.23; 95% CI 1.38-3.60), perceived stigma (AOR
2.47; 95% CI 1.59-3.83), medication adherence (AOR 2.85; 95% CI 1.64-4.96), and
current substance use (AOR 2.10; 95% CI 1.34-3.30). Conclusion: There is a high
prevalence of depression among epilepsy patients. Early detection and prompt
management of depressive symptoms are critically important in reducing depression
burden among people living with epilepsy.
PMID- 29942343
TI - Occupational infection and needle stick injury among clinical laboratory workers
in Al-Madinah city, Saudi Arabia.
AB - Background: Clinical laboratory workers face biohazard such as needlestick injury
and occupational infection on a daily basis. In this study, we examined self
reported frequency of occupational infection and needlestick injury among the
clinical laboratory workers in Al- Madinah, Saudi Arabia. Methods: A total of 234
clinical laboratory workers were recruited from private and government health
sectors to answer a self-administered questionnaire that was prepared to achieve
the aims of the study. Results: The results showed that approximately 33% of the
sample had an experienced occupational infection while 24% had experienced a
needlestick injury. Approximately, 49% reported that they always recap needle
after use, whereas 15% reported doing that most of the times. Occupational
infection, needlestick injury and recapping needles after use were associated
with lack of training on biosafety (P < 0.05). Conclusion: The frequency of
occupational infection and needlestick injury among clinical laboratory workers
in Al-Madinah is high. Interventions related to biosafety and infection control
and the use of needlestick prevention devices might be useful in lowering such
frequency.
PMID- 29942344
TI - Cryopreservation of virus: a novel biotechnology for long-term preservation of
virus in shoot tips.
AB - Background: Preservation of plant virus is a fundamental requirement in all types
of virus-related research and applied applications. Development of efficient,
reliable strategies for long-term preservation of plant virus would largely
assist these studies. Results: The present study reported a novel biotechnology
allowing cryopreservation of Apple stem grooving virus (ASGV) in living shoot
tips. Following cryopreservation by droplet-vitrification or encapsulation
dehydration, about 62-67% of shoot regrowth and 100% of ASGV cryopreservation
were obtained. Although shoot proliferation and virus concentration were reduced
in cryopreserved diseased shoots after 8 weeks of shoot regeneration, continuous
subculture for 4 times (16 weeks) increased shoot proliferation and virus
concentration to comparative levels as those produced by shoot tip culture (as a
control to shoot tip cryopreservation). Cryopreserved ASGV was efficiently
transmitted to a woody plant by micrografting and to a herbaceous indicator by
mechanical inoculation. Gene sequencing in three fragments of ASGV genome
including coat protein and movement protein showed that cryopreserved ASGV shared
99.87% nucleotide identities with shoot tip culture-preserved virus, indicating
cryopreserved virus is genetically stable. Conclusions: The present study
demonstrates ASGV, a representative virus that can infect meristematic cells of
shoot tips, can be efficiently cryopreserved in shoot tips. To the best of our
knowledge, this is the first report on plant virus cryopreservation in living
tissues, and has great potential applications to long-term preservation of plant
viruses.
PMID- 29942345
TI - An aerated axenic hydroponic system for the application of root treatments:
exogenous pyruvate as a practical case.
AB - Background: Hydroponic systems are a convenient platform for plant cultivation
when treatments are applied to the roots because they provide precise control of
the composition of the growth medium, ensuring the availability of different
compounds. A problem arises when axenic conditions are needed but the treatment
of choice (exogenous organic acids or sugars) promote the growth of unwanted
microorganisms. Moreover, axenic conditions are usually applied in liquid and
semi-liquid growing systems, where oxygen availability can be compromised, if no
aeration is provided. Results: The driver for the development of this hydroponic
system was the application of the organic acid pyruvate to the roots of plants
grown under aerated axenic conditions. No contamination was detected in the
nutrient solution, even after the addition of pyruvate. The system was validated
in pea plants treated with either pyruvate or herbicides inhibiting amino acid
biosynthesis. The effects on ethanol fermentation were compared by analysing the
enzymatic activity, protein content and transcriptional levels in plants treated
with either pyruvate or herbicides. Conclusions: The developed system enables the
study of the exogenous application of organic acids in the nutrient solution
under axenic conditions and without oxygen limitation. This system allows the
study of the effect of any type of treatments applied to roots under aerated
axenic hydroponic systems at physiological and molecular levels. The role of
pyruvate in the induction of fermentation by herbicides cannot be simply
explained by an increase in substrate availability.
PMID- 29942346
TI - Development of a reconditioning program for elderly abdominal surgery patients:
the Elder-friendly Approaches to the Surgical Environment-BEdside reconditioning
for Functional ImprovemenTs (EASE-BE FIT) pilot study.
AB - Background: Elderly individuals who are hospitalized due to emergency abdominal
surgery spend over 80% of their recovery time in bed, resulting in early and
rapid muscle loss. As these elderly individuals have a lower physiological
reserve, the impact of muscle wasting on function may be profound. The objectives
of this study are to (1) create an independently led post-surgical reconditioning
program and (2) pilot its implementation, while assessing the feasibility and
safety of the program. Methods: The BE FIT program was generated with hospital
rehabilitation staff to target lower limb strength, balance, and endurance. This
pilot study was assessed using a sequential before and after trial, with a cohort
of patients aged >= 65 years enrolled in the Elder-friendly Approaches to the
Surgical Environment (EASE) study. Change in 30-s sit-to-stand performance
between postoperative day 2 and discharge was compared between Usual Care pre-
and post-BE FIT participants. Results: A total of 66 patients participated in the
sub-study, 33 Usual Care and 33 BE FIT. Mean (SD) age was 76.2 (8.78); 44 (67%)
were female, with 11 (17%) reporting mild/moderate frailty on the CHSA Clinical
Frailty Scale. BE FIT participants had a median of three rehab days and self
reported completing an average of 83% of the exercises. The adjusted between
group difference showed that the BE FIT patients were able to complete more
stands than the Usual Care (1.9 stands (0.94), p = 0.05). There were no reported
adverse events. Conclusion: The reconditioning program was shown to be safe and
feasible within the hospital setting for the elderly emergency abdominal surgery
patients. More rigorous assessment is needed to confirm this effectiveness and to
better assess patient adherence to self-directed exercise. Trial registration:
Registration #NCT02233153 through ClinicalTrials.gov. Registered September 8,
2014.
PMID- 29942347
TI - Clinico-pathological features of oropharyngeal squamous cell carcinomas in
Malaysia with reference to HPV infection.
AB - Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has
been rising in Western countries and this has been attributed to human
papillomavirus (HPV) infection. p16 expression is a marker for HPV infection and
p16 positive OPSCC is now recognized as a separate disease entity. There are only
limited data available regarding HPV-related OPSCC in Asian countries and no data
from Malaysia. Methods: We identified 60 Malaysian patients with OPSCC over a 12
year period (2004-2015) from four different hospitals in two major cities, Kuala
Lumpur and Penang. The detection of HPV was carried out using p16
immunohistochemistry and high risk HPV DNA in situ hybridisation. Results:
Overall, 15 (25%) tumours were p16 positive by immunohistochemistry, 10 of which
were also positive for high risk HPV DNA by in situ hybridisation. By comparison,
a matched cohort of UK patients had a p16 positive rate of 49%. However, between
2009 and 2015, where cases were available from all four hospitals, 13 of 37 (35%)
cases were p16 positive. In our Malaysian cohort, 53% of patients were of Chinese
ethnicity and 80% of the p16 positive cases were found in these patients; no
Indian patients had p16 positive disease, despite representing 35% of the total
cohort. Conclusion: The proportion of OPSCCs associated with HPV in Malaysia
appears to be lower than in European and American cohorts and could possibly be
more prevalent amongst Malaysians of Chinese ethnicity. Further, our data
suggests that the burden of HPV-related OPSCC could be increasing in Malaysia.
Larger cross-sectional studies of Malaysian patients are required to determine
the public health implications of these preliminary findings.
PMID- 29942348
TI - Correction to: Proximity ligation scaffolding and comparison of two Trichoderma
reesei strains genomes.
AB - [This corrects the article DOI: 10.1186/s13068-017-0837-6.].
PMID- 29942349
TI - Incidence of early postoperative complications requiring surgical revision for
recurrent lumbar disc herniation after spinal surgery: a retrospective
observational study of 9,310 patients from the German Spine Register.
AB - Background: The recurrence rate in lumbar disc herniations (LDH) has been
reported between 5 and 25%. There are only few data about this phenomenon that
occurs within days of the initial operation. We analyse early recurrent LDH by
analysis of data from the German Spine register. Methods: Data from patients
undergoing disc herniation surgery in the lumbar region were extracted from the
German Spine Registry between 1st January 2012 and 31st December 2016. Patients
with early recurrent LDH within days of initial surgery were separately analysed.
Results: A total of 9310 surgeries for LDH were documented in the German Spine
Register. From these patients 115 (1.2%) presented an early recurrent disc
surgeries within days of the initial surgery. The mean age was 70 +/- 2.50 years.
Most affected segment was L4/5 (47 cases, 41%), followed by L3/4 (45 cases, 39%).
The most of our patients showed a normal or overweight Body Mass Index. Surgery
for early recurrent LDH was associated with a high rate of incidental durotomies
(20 cases, 17.6%). In 3 cases (2.6%) therapy with a lumbar drain was necessary.
Conclusions: The rate of early recurrent LDH within days of surgery is 1.2%. Age
seems to be an important factor in early recurrent LDH while obesity does not.
The data of the German Spine Register seems to have a reliable data collection
system that can perform multicentre data analysis. The databases from this
Register could be used in the future for various purposes, such as the evaluation
of multicentre surgical techniques, results in patients with various surgical
procedures and basic research in spine surgery.
PMID- 29942350
TI - Characterizing the effects of missing data and evaluating imputation methods for
chemical prioritization applications using ToxPi.
AB - Background: The Toxicological Priority Index (ToxPi) is a method for
prioritization and profiling of chemicals that integrates data from diverse
sources. However, individual data sources ("assays"), such as in vitro bioassays
or in vivo study endpoints, often feature sections of missing data, wherein
subsets of chemicals have not been tested in all assays. In order to investigate
the effects of missing data and recommend solutions, we designed simulation
studies around high-throughput screening data generated by the ToxCast and Tox21
programs on chemicals highlighted by the Agency for Toxic Substances and Disease
Registry's (ATSDR) Substance Priority List (SPL), which helps prioritize
environmental research and remediation resources. Results: Our simulations
explored a wide range of scenarios concerning data (0-80% assay data missing per
chemical), modeling (ToxPi models containing from 160-700 different assays), and
imputation method (k-Nearest-Neighbor, Max, Mean, Min, Binomial, Local Least
Squares, and Singular Value Decomposition). We find that most imputation methods
result in significant changes to ToxPi score, except for datasets with a small
number of assays. If we consider rank change conditional on these significant
changes to ToxPi score, we find that ranks of chemicals in the minimum value
imputation, SVD imputation, and kNN imputation sets are more sensitive to the
score changes. Conclusions: We found that the choice of imputation strategy
exerted significant influence over both scores and associated ranks, and the most
sensitive scenarios were those involving fewer assays plus higher proportions of
missing data. By characterizing the effects of missing data and the relative
benefit of imputation approaches across real-world data scenarios, we can augment
confidence in the robustness of decisions regarding the health and ecological
effects of environmental chemicals.
PMID- 29942351
TI - Plecanatide: a new guanylate cyclase agonist for the treatment of chronic
idiopathic constipation.
AB - Chronic constipation affects millions of Americans, consumes significant
healthcare resources, and significantly affects quality of life (QOL). Recently,
several new treatment options have become available for the treatment of
constipation, including intestinal secretagogues such as lubiprotone, and
linaclotide, prokinetics such as prucalopride, and bile acid transporter
antagonists. Plecanatide is the newest of the secretagogue class of compounds
that has been approved by the US Food and Drug Administration for the treatment
of adults with chronic idiopathic constipation (CIC) in the USA. It is a
guanylate cyclase agonist, and a 16 amino acid synthetic peptide that is a
structural analog of human uroguanylin. Two large randomized, double-blind,
placebo-controlled studies assessed the efficacy and safety of plecanatide in CIC
patients (Rome III). Both doses of plecanatide, 3 mg and 6 mg resulted in a
significantly greater percentage of patients who were durable overall complete
spontaneous bowel movement (CSBM) responders (primary endpoint) compared with
those who received placebo (plecanatide 3 mg, 21.0%; plecanatide 6 mg, 19.5%;
placebo, 10.2%; p < 0.001 for each drug dose versus placebo). Plecanatide
treatment also significantly reduced the severity of other CIC symptoms
(straining effort, stool consistency, bloating). Also, plecanatide-treated
patients reported high levels of satisfaction and improved QOL and desire to
continue treatment. The rate of treatment-emergent adverse events with
plecanatide was low, including rates of diarrhea (5%). Plecanatide is a luminally
acting secretagogue that is efficacious and safe for the treatment of CIC. This
article provides an overview of plecanatide in the management of adults with CIC.
PMID- 29942352
TI - The upper limit for TSH during pregnancy: why we should stop using fixed limits
of 2.5 or 3.0 mU/l.
AB - Physiological changes necessitate the use of pregnancy-specific reference ranges
for TSH and FT4 to diagnose thyroid dysfunction during pregnancy. Although many
centers use fixed upper limits for TSH of 2.5 or 3.0 mU/L, this comment
describeds new data which indicate that such cut-offs are too low and may lead to
overdiagnosis or even overtreatment. The new guidelines of the American Thyroid
Association have considerably changed recommendations regarding thyroid function
reference ranges in pregnancy accordingly. Also a stepwise approach to
interpreting these guidelines is discussed as well as the relevant role of FT4 in
diagnosis.
PMID- 29942353
TI - Sociology of the professions: what it means for podiatry.
AB - Background: The health professions have progressed and evolved considerably over
the last few decades in response to demographic, technological, societal and
political changes. They continue to do so as the volume and complexity of
population health needs steadily increase. Role boundary expansion is among the
key changes to the health professions, including podiatry to meet demand.
Nonetheless podiatry's role boundary expansion has not been achieved swiftly or
without resistance from neighbouring and dominant professions. This paper seeks
to explain the nature of this resistance with respect to the sociology of the
professions literature and to shed light on some of the factors and processes at
play when role boundary changes arise in health care. Discussion: Six of the most
contemporaneously relevant sociology of the professions theories are summarised:
Taxonomic, Marxian, Bourdieusian, Foucauldian, Boundary Work and Neo-Weberian
paradigms. Conclusion: This review highlights that some paradigms are more
relevant than others in the current socio-political landscape. It also
illustrates that there is a common theme underlying each approach to defining the
professions and their boundaries: competition. This may help health
professionals, including podiatrists, to understand and manage the challenges and
resistance experienced when professions attempt to expand role boundaries to meet
increasing and changing population health needs.
PMID- 29942354
TI - Key lime (Citrus aurantifolia) inhibits the growth of triple drug resistant
Helicobacter pylori.
AB - Background: Eradication rate for Helicobacter pylori (H. pylori) has decreased
due to antibiotic resistance. Therefore, new strategies are needed to enhance H.
pylori eradication, especially for H. pylori with high antibiotic resistance. The
objective of this study was to evaluate anti-H. pylori activities of constituents
from key lime (Citrus aurantifolia) and their possible inhibitory effects on
urease activity of H. pylori. Methods: Helicobacter pylori strain ATCC 43526 and
triple drug resistant (TDR) H. pylori strains were used in this study. Urease
activities of H. pylori strains were measured by ammonia colorimetrical
quantification using ELISA reader. Minimum inhibitory concentrations were
determined by agar dilution method for antibiotics and by modified media dilution
method for each constituent of Citrus aurantifolia (C. aurantifolia). Results:
Citrus aurantifolia extract decreased the number of colonies of H. pylori strain
ATCC 43526 and TDR H. pylori stains. An increasing concentration of C.
aurantifolia extract attenuated urease activities of H. pylori strain ATCC 43526
and TDR H. pylori strains. Among constituents of C. aurantifolia, citral and 4
hexen-3-one were found to be able to inhibit the growth of H. pylori strain ATCC
43526 and TDR H. pylori strains. Furthermore, citral and 4-hexen-3-one inhibited
urease activities of H. pylori strain ATCC 43526 and TDR H. pylori strains in a
dose-dependent manner. Conclusion: Citrus aurantifolia has antimicrobial effect
on TDR H. pylori strains, suggesting that C. aurantifolia might have therapeutic
potential to control antibiotic-resistant H. pylori strains that cause
eradication failure using other antibiotics.
PMID- 29942355
TI - Takayasu's arteritis associated with eosinophilic gastroenteritis, possibly via
the overactivation of Th17.
AB - Background: Takayasu's arteritis (TA) is a large-vessel vasculitis pathologically
characterized by granulomatous necrotizing vasculitis with giant cells. Although
the cause of TA is still unclear, genetic factors as well as immunological
abnormalities, particularly the overactivation of Th1 and Th-17, are considered
to play important roles in the pathogenesis of this disease. Eosinophilic
gastroenteritis (EGE) is a type of refractory inflammation in which numerous
eosinophils infiltrate the inflammatory area. It is known that the overactivation
of Th2 is associated with the pathogenesis of EGE, although the cause of EGE is
still unclear. The immunological abnormalities in TA are therefore thought to be
different from those in EGE. To date, no cases of complication of TA and EGE have
been reported. Case presentations: An 18 year-old female was diagnosed with EGE
and treated with prednisolone. At 6 months after completion of the treatment, the
patient experienced chest pain, and was diagnosed with TA. TH1 and TH17 immunity
are thought to be involved with TA, while TH2 are considered to be involved with
EGE. In this case, the expression of IL-17 mRNA in the colon mucosa greatly
decreased after prednisolone treatment for EGE. Conclusions: This is the first
report of TA complicated with EGE, and the overactivation of TH17 is considered
to be associated with the pathogenesis of these two diseases.
PMID- 29942356
TI - Coenzyme Q10 suppresses apoptosis of mouse pancreatic beta-cell line MIN6.
AB - Background: In mitochondrial diabetes, apoptosis of beta-cells caused by
mitochondrial stress plays an important role in impaired insulin secretion.
Several studies have reported that coenzyme Q10 (CoQ10) has therapeutic effects
on mitochondrial diabetes, but no reports have examined the fundamental
effectiveness or mechanism of CoQ10 in mitochondrial diabetes. We previously
reported in a Japanese article that CoQ10 has protective effects on pancreatic
beta-cells against mitochondrial stress using mouse pancreatic beta-cell line
MIN6 and staurosporine (STS). Here, we report that CoQ10 protects MIN6 cells
against apoptosis caused by STS and describe the more detailed apoptotic cascade.
Methods: Apoptosis of MIN6 cells was induced by 0.5 uM STS treatment for specific
periods with or without 30 MUM CoQ10. The apoptosis cascade in MIN6 cells was
then investigated using WST-8 assays, annexin-V staining, western blotting, and
DNA degradation analysis. Results: Sixteen hours of 0.5 MUM STS treatment led to
47% cell viability, but pretreatment with 30 MUM CoQ10 resulted in significantly
higher viability of 76% (P < 0.01). CoQ10 also prevented translocation of
phosphatidylserine from the inner leaflet to the outer leaflet of the cell
membrane. CoQ10 prevented cytochrome c release from mitochondria and activation
of caspase-3. Conclusion: We concluded that CoQ10 protects pancreatic beta-cells
through anti-apoptotic effects against STS treatment.
PMID- 29942357
TI - Impact of socioeconomic status on adverse cardiac events after coronary
angioplasty: a cohort study.
AB - Background: Socioeconomic status (SES) has been associated with adverse
cardiovascular events in coronary atherosclerotic disease. However, it is unclear
how SES impacts adverse cardiac events in patients treated with percutaneous
coronary intervention (PCI). Methods: We determined SES based on educational,
economic and occupational parameters for 630 consecutive patients who underwent
PCI at our centre between 01 June 2015 and 01 June 2016. The patients were
divided into low and high SES groups, and they were followed up for 12 months.
Patients were matched at baseline for demographic and procedural characteristics;
multivariate analysis was used to adjust for baseline and procedural variables.
Postprocedure compliance to medications was analysed. At 12 months, the primary
composite end point of major adverse cardiac events (MACE) - consisting of death,
non-fatal myocardial infarction, target lesion revascularisation, target vessel
revascularisation - was compared between the groups. Results: The high SES group
had a higher prevalence of diabetes mellitus (p=0.03; OR 0.74%, 95% CI 0.53% to
1.03%) and a stronger family history of ischaemic heart disease (p=0.003; OR
0.53%, 95% CI 0.33% to 0.84%). Low SES was associated with lower compliance with
medication (p=0.01; OR 2.22%, 95% CI 1.19% to 4.15%). At 12 months, the primary
composite end point of MACE was found to be higher in the low SES group (p=0.01);
higher MACE was primarily driven by cardiac mortality (p<0.001). Low SES was
found to be an independent predictor of MACE (HR 1.84%, 95% CI 1.16% to 2.96%).
Conclusion: Low SES was associated with a higher incidence of major adverse
cardiac events in patients undergoing PCI and was an independent predictor of
MACE at 12 months.
PMID- 29942358
TI - Extended trans-septal versus left atrial approach in mitral valve surgery: 1017
patients' experience.
AB - Objective: The mitral valve may be accessed directly through the left atrium but
visualisation can sometimes be challenging. A trans-septal interatrial approach
provides better exposure and easy access for concomitant tricuspid procedures
especially in difficult cases. This retrospective study evaluates the safety and
effectiveness of the extended vertical trans-septal approach (EVTSA) for routine
mitral valve exposure. Method: 1017 consecutive patients undergoing an isolated
primary mitral valve procedure (repair/replacement) through a median sternotomy
were retrospectively studied between 2000 and 2015. Up to 135 patients were
operated by EVTSA (group A) while 882 patients underwent a traditional left
atrial (LA, group B) approach. Results: There were 135 patients (M/F=56/79) in
group A and 882 patients (M/F=398/484) in group B. Logistic EuroSCORE was
significantly lower in EVTSA group (0.61 vs 0.90, p=0.000001). In the LA group
there were more patients with preoperative transient ischaemic attack or stroke
(94 vs 6, p=0.005). Cumulative cross-clamp time was 82 (44-212) min (EVTSA group)
and 78 (30-360) min (LA group) (p=0.271) while cardiopulmonary bypass time was
107 (58-290) and 114 (43-602) min, respectively (p=0.121).Postoperative blood
loss was 415 mL (EVTSA) vs 427 mL (LA) (p=0.273). No significant difference was
found in the incidence of postoperative atrial fibrillation (p=0.22) or heart
block requiring permanent pacemaker (p=0.14). Conclusion: In our opinion, EVTSA
to the mitral valve is safe and reproducible. It gives excellent exposure of the
mitral valve under all circumstances without any significant increase in cross
clamp or bypass time, postoperative arrhythmia, heart block/pacemaker rate or
bleeding.
PMID- 29942359
TI - Influence of comorbidities and clinical prediction model on neurological
prognostication post out-of-hospital cardiac arrest.
AB - Background: Survival with good neurological function post out-of-hospital cardiac
arrest (OHCA), defined as cerebral performance category (CPC) 1-2, ranges from
1.6% to 3% in Asia. We aim to study the influence of comorbidities and peri-OHCA
event factors on neurological recovery and develop a model that can help
clinicians predict neurological function among patients with post-OHCA admitted
to the hospital. Methods: This was a retrospective cohort study. All patients
admitted post-OHCA from 1 January 2011 to 31 December 2015 to a tertiary centre
were identified through the hospital OHCA registry. Patients who survived till
hospital admission were included. Logistic regression was used to identify
patient and peri-arrest factors that were significantly associated with survival
with CPC 1-2. The significant factors for survival with CPC 1-2 were then put
into a multivariable model and the discriminative ability was tested using the
receiver operator characteristic (ROC) curve. Calibration and internal validation
of the model were also performed. External validation in a small prospective
cohort was also performed. Results: In our derivation cohort of 129 patients,
30.23% survived with CPC 1-2. Significant factors associated with survival with
good neurological outcomes were age-adjusted Charlson Comorbidity Index <=5, time
to first return of spontaneous circulation <=40 min, the presence of immediate
bystander cardiopulmonary resuscitation and shockable rhythms. We also developed
a nomogram which showed good internal (ROC curve 0.84; 95% CI 0.77 to 0.91) and
external validation (ROC curve 0.90; 95% CI 0.81 to 1.00).
PMID- 29942360
TI - A challenging broad-complex tachycardia.
AB - : A 53-year-old man presented with chest pain, palpitations and presyncope,
without history of overt cardiac disease. The patient was alert. His heart rate
was 206 beats per minute, and his blood pressure was 100/50 mm Hg. An intravenous
bolus of amiodarone 150 mg was administered in the emergency department. His ECGs
preamiodarone and postamiodarone are shown in figure 1. Echocardiography showed
low-normal left ventricular systolic function.Figure 1(A) ECG of index
arrhythmia. (B) ECG following amiodarone. Question: What should the next
diagnostic test be?Referral for electrophysiology study.Referral for urgent
coronary angiography.12-lead ECG with posterior lead placement.Bedside adenosine
challenge.
PMID- 29942361
TI - Vasculitis of ascending aorta detected on FDG PET/CT in a patient with fever of
unknown origin.
PMID- 29942362
TI - The clinical potential of romosozumab for the prevention of fractures in
postmenopausal women with osteoporosis.
AB - The glycoprotein sclerostin inhibits activation of the canonical Wnt pathway and
thereby suppresses bone formation by inhibiting the osteoblasts. Additionally,
sclerostin increases bone resorption by stimulating the production of receptor
activator of nuclear factor kappa-beta-ligand (RANKL). Romosozumab (ROMO) is a
monoclonal antibody against sclerostin. Phase III clinical trials in
postmenopausal women with osteoporosis have shown that ROMO increases bone
mineral density at the lumbar spine and hip and reduces the risk of vertebral and
clinical fractures in comparison with placebo. In women with severe osteoporosis,
ROMO reduces the risk of vertebral, nonvertebral and clinical fractures in
comparison with alendronate. ROMO is the first treatment for osteoporosis with
dual action, and may become a valuable tool for improving the treatment of
osteoporosis. At present, the approval of ROMO by the authorities is awaiting
further investigations of a potential increased risk of cardiovascular events
associated with ROMO treatment.
PMID- 29942364
TI - Ankylosing spondylitis and axial spondyloarthritis: recent insights and impact of
new classification criteria.
AB - Development of the Assessment in Spondyloarthritis International Society (ASAS)
classification criteria for axial spondyloarthritis (SpA) was one of the major
breakthroughs in the field over the past decade. Despite some concerns related to
the specificity of the criteria, they stimulated research into the early stage of
the disease. This resulted in major advances in the understanding of the course
of the disease, revealing predictors of progression, improvement in early
diagnosis and treatment in axial SpA. In this review, we summarize the recent
developments resulting from the introduction of the ASAS classification criteria
for axial SpA and the implications for research and clinical practice.
PMID- 29942363
TI - The role of the JAK/STAT signal pathway in rheumatoid arthritis.
AB - Proinflammatory cytokine activation of the Janus kinase/signal transducers and
activators of transcription (JAK/STAT) signal transduction pathway is a critical
event in the pathogenesis and progression of rheumatoid arthritis. Under normal
conditions, JAK/STAT signaling reflects the influence of negative regulators of
JAK/STAT, exemplified by the suppressor of cytokine signaling and protein
inhibitor of activated STAT. However, in rheumatoid arthritis (RA) both of these
regulators are dysfunctional. Thus, continuous activation of JAK/STAT signaling
in RA synovial joints results in the elevated level of matrix metalloproteinase
gene expression, increased frequency of apoptotic chondrocytes and most
prominently 'apoptosis resistance' in the inflamed synovial tissue. Tofacitinib,
a JAK small molecule inhibitor, with selectivity for JAK2/JAK3 was approved by
the United States Food and Drug Administration (US FDA) for the therapy of RA.
Importantly, tofacitinib has demonstrated significant clinical efficacy for RA in
the post-US FDA-approval surveillance period. Of note, the success of tofacitinib
has spurred the development of JAK1, JAK2 and other JAK3-selective small molecule
inhibitors, some of which have also entered the clinical setting, whereas other
JAK inhibitors are currently being evaluated in RA clinical trials.
PMID- 29942365
TI - Transposable elements and gene expression during the evolution of amniotes.
AB - Background: Transposable elements (TEs) are primarily responsible for the DNA
losses and gains in genome sequences that occur over time within and between
species. TEs themselves evolve, with clade specific LTR/ERV, LINEs and SINEs
responsible for the bulk of species-specific genomic features. Because TEs can
contain regulatory motifs, they can be exapted as regulators of gene expression.
While TE insertions can provide evolutionary novelty for the regulation of gene
expression, their overall impact on the evolution of gene expression is unclear.
Previous investigators have shown that tissue specific gene expression in
amniotes is more similar across species than within species, supporting the
existence of conserved developmental gene regulation. In order to understand how
species-specific TE insertions might affect the evolution/conservation of gene
expression, we have looked at the association of gene expression in six tissues
with TE insertions in six representative amniote genomes. Results: A novel
bootstrapping approach has been used to minimise the conflation of effects of
repeat types on gene expression. We compared the expression of orthologs
containing recent TE insertions to orthologs that contained older TE insertions,
and the expression of non-orthologs containing recent TE insertions to non
orthologs with older TE insertions. Both orthologs and non-orthologs showed
significant differences in gene expression associated with TE insertions. TEs
were found associated with species-specific changes in gene expression, and the
magnitude and direction of expression changes were noteworthy. Overall, orthologs
containing species-specific TEs were associated with lower gene expression, while
in non-orthologs, non-species specific TEs were associated with higher gene
expression. Exceptions were SINE elements in human and chicken, which had an
opposite association with gene expression compared to other species. Conclusions:
Our observed species-specific associations of TEs with gene expression support a
role for TEs in speciation/response to selection by species. TEs do not exhibit
consistent associations with gene expression and observed associations can vary
depending on the age of TE insertions. Based on these observations, it would be
prudent to refrain from extrapolating these and previously reported associations
to distantly related species.
PMID- 29942366
TI - Horizontal transfer and proliferation of Tsu4 in Saccharomyces paradoxus.
AB - Background: Recent evidence suggests that horizontal transfer plays a significant
role in the evolution of of transposable elements (TEs) in eukaryotes. Many cases
of horizontal TE transfer (HTT) been reported in animals and plants, however
surprisingly few examples of HTT have been reported in fungi. Findings: Here I
report evidence for a novel HTT event in fungi involving Tsu4 in Saccharomyces
paradoxus based on (i) unexpectedly high similarity between Tsu4 elements in S.
paradoxus and S. uvarum, (ii) a patchy distribution of Tsu4 in S. paradoxus and
general absence from its sister species S. cerevisiae, and (iii) discordance
between the phylogenetic history of Tsu4 sequences and species in the
Saccharomyces sensu stricto group. Available data suggests the HTT event likely
occurred somewhere in the Nearctic, Neotropic or Indo-Australian part of the S.
paradoxus species range, and that a lineage related to S. uvarum or S. eubayanus
was the likely donor species. The HTT event has led to massive proliferation of
Tsu4 in the South American lineage of S. paradoxus, which exhibits partial
reproductive isolation with other strains of this species because of multiple
reciprocal translocations. Full-length Tsu4 elements are associated with both
breakpoints of one of these reciprocal translocations. Conclusions: This work
shows that comprehensive analysis of TE sequences in essentially-complete genome
assemblies derived from long-read sequencing provides new opportunities to detect
HTT events in fungi and other organisms. This work also provides support for the
hypothesis that HTT and subsequent TE proliferation can induce genome
rearrangements that contribute to post-zygotic isolation in yeast.
PMID- 29942367
TI - Nice Finish to 2014 and Looking Forward to 2015.
AB - This editorial article summarizes last year's achievements and current plans for
2015 that focuses on attracting a high quality, variety of articles with more
emphasis in engaging with academia and industry in the field of nanotechnology
and biomedical research.
PMID- 29942368
TI - Influence of Growth Parameters on the Formation of Hydroxyapatite (HAp)
Nanostructures and Their Cell Viability Studies.
AB - Morphology controlled hydroxyapatite (HAp) nanostructures play a vital role in
biomedical engineering, tissue regenerative medicine, biosensors,
chemotherapeutic applications, environmental remediation, etc. The present work
investigates the influence of temperature, pH and time on the growth of HAp
nanostructures using a simple, cost effective and surfactant free chemical
approach. The obtained HAp nanostructures were systematically investigated by
analytical techniques such as XRD, FESEM, EDX, FTIR and Raman spectroscopy. The
XRD analysis showed that the hexagonal structure of the hydroxyapatite and
average crystallite size was estimated from this analysis. The electron
microscopic analysis confirmed the different morphologies obtained by varying the
synthesis parameters such as temperature, pH and time. The elemental composition
was determined through EDS analysis. FTIR and Raman spectroscopic analysis
confirmed the presence of functional groups and the purity and crystallinity of
the samples. The biocompatibility and adhesion nature of samples was examined
with mouse preosteoblast cells. The obtained results demonstrated good
biocompatibility and excellent focal adhesion.
PMID- 29942369
TI - Lab-on-a-Tip (LOT): Where Nanotechnology Can Revolutionize Fibre Optics.
AB - Recently developed lab-on-a-chip technologies integrate multiple traditional
assays on a single chip with higher sensitivity, faster assay time, and more
streamlined sample operation. We discuss the prospects of the lab-on-a-tip
platform, where assays can be integrated on a miniaturized tip for in situ and in
vivo analysis. It will resolve some of the limitations of available lab-on-a-chip
platforms and enable next generation multifunctional in vivo sensors, as well as
analytical techniques at the single cell or even sub-cellular levels.
PMID- 29942370
TI - A Microfluidic Platform Containing Sidewall Microgrooves for Cell Positioning and
Trapping.
AB - Microfluidic channels enable the control of cell positioning and the capturing of
cells for high-throughput screening and other cellular applications. In this
paper, a simple microfluidic platform is proposed for capturing small volumes of
cells using sidewall microgrooves. The cell docking patterns in the channels
containing sidewall microgroove are also studied. Both numerical and experimental
investigations are performed within channels containing sidewall microgrooves of
three different widths (i.e., 50, 100 and 200 MUm). It is observed that channels
containing sidewall microgrooves play an important role in regulating cell
positioning and patterning. The obtained results revealed that 10 to 14 cells
were positioned inside the sidewall channels of 200 MUm width, two to five cells
were positioned within the channels of 100 MUm width, and one to two individual
cells were docked within the sidewall channel of 50 MUm width. Particle modelling
shows the prediction of cell positioning within sidewall microgrooves. The
positions of cells docked within microgroove-containing channels were also
quantified. Furthermore, the shear stress variation and cell positioning in the
sidewall microgrooves were correlated. Therefore, these sidewall microgroove
containing channels could be potentially useful for regulating cell positioning
and patterning on two-dimensional surfaces, three-dimensional microenvironments
and high-throughput screening. Cell patterning and positioning are of great
importance in many biological applications, such as drug screening and cell-based
biosensing.
PMID- 29942371
TI - Multiple Sclerosis and the LIF/IL-6 Axis: Use of Nanotechnology to Harness the
Tolerogenic and Reparative Properties of LIF.
AB - Leukaemia inhibitory factor (LIF) plays a critical role in "stemness" versus
"differentiation", a property that underpins the core value of LIF as a
therapeutic for both the treatment of autoimmune disease and for promoting tissue
repair. This value can be realized using nano-engineering technology, where a new
generation of tools can, with unprecedented ability, manipulate biological
functions. One striking example is the treatment of multiple sclerosis (MS). The
underpinning biology is the newly identified LIF/IL-6 axis in T lymphocytes,
which can tilt the behaviour between immune tolerance versus immune attack. This
LIF/IL-6 axis is ideally suited to nanotherapeutic manipulation, given its
inherent mechanistic simplicity of two mutually opposing feed-forward loops that
determine either tolerogenic (LIF) or inflammatory (IL-6) immunity. Using LIF
that is formulated in biodegradable nanoparticles (LIF-NP) and targeted to CD4+ T
cells, the axis is harnessed towards immune tolerance. This has implications for
the treatment of autoimmune diseases, where the clinical burden is immense. It
encompasses more than 100 diseases and, in the USA alone, costs more than $100
billion in direct health care costs annually. Other properties of LIF include the
promotion of healthy neuro-glial interactions within the central nervous system
(CNS), where, in addition to MS, LIF-NP therapy is relevant to inflammatory
neurodegenerative diseases that represent a large and increasing need within
aging populations. Thirdly, LIF is a reparative growth factor that can maintain
genomic plasticity. LIF-NP supports the use of stem cell-based therapies in
regenerative medicine plus augment therapeutic benefits within the patient. These
core properties of LIF are greatly amplified in value by the advantage of being
formulated as nanoparticles, namely (i) targeted delivery, (ii) exploitation of
endogenous regulatory pathways and (iii) creation of surrogate micro-stromal
niches. We discuss LIF-NP as a means to harness endogenous pathways for the
treatment of MS, both to reset immune self-tolerance and to promote repair of
myelin that is required to support health within the nervous system.
PMID- 29942372
TI - In Vitro AuNPs' Cytotoxicity and Their Effect on Wound Healing.
AB - Recently, due to their unique properties, gold nanoparticles (AuNPs) have been
used in many biological applications. However, little is known about their
toxicity when they come into contact with a biological system. Based on the
proposal that AuNPs can have a positive effect on wound healing, the present
study investigated the influence of negatively-charged-surface AuNPs (average
diameter 25-50 nm) on the viability of normal human dermal fibroblasts (NHDF) and
normal human epidermal keratinocytes (NHEK). Moreover, we evaluated the effect of
AuNPs on the secretion of proteins involved in wound healing, such as interleukin
8 and - 12 (IL-8, IL-12), tumour necrosis factor-alpha (TNF-alpha), vascular
endothelial growth factor (VEGF), basic fibroblast grow factor (bFGF), and
granulocyte-macrophage colony-stimulating factor (GM-CSF). The results showed
that AuNPs were not toxic to NHDF and NHEK. They showed a decrease in AuNPs'
production of pro-inflammatory cytokines IL-6, IL-12 and TNF-alpha, as well as
proteins involved in angiogenesis such as VEGF and bFGF. Thus, we suggest that
AuNPs could have anti-inflammatory and anti-angiogenic activity.
PMID- 29942373
TI - Single-Molecule Detection in Nanogap-Embedded Plasmonic Gratings.
AB - We introduce nanogap-embedded silver plasmonic gratings for single-molecule (SM)
visualization using an epifluorescence microscope. This silver plasmonic platform
was fabricated by a cost-effective nano-imprint lithography technique, using an
HD DVD template. DNA/ RNA duplex molecules tagged with Cy3/Cy5 fluorophores were
immobilized on SiO2-capped silver gratings. Light was coupled to the gratings at
particular wavelengths and incident angles to form surface plasmons. The SM
fluorescence intensity of the fluorophores at the nanogaps showed approximately a
100-fold mean enhancement with respect to the fluorophores observed on quartz
slides using an epifluorescence microscope. This high level of enhancement was
due to the concentration of surface plasmons at the nanogaps. When nanogaps
imaged with epifluorescence mode were compared to quartz imaged using total
internal reflection fluorescence (TIRF) microscopy, more than a 30-fold mean
enhancement was obtained. Due to the SM fluorescence enhancement of plasmonic
gratings and the correspondingly high emission intensity, the required laser
power can be reduced, resulting in a prolonged detection time prior to
photobleaching. This simple platform was able to perform SM studies with a low
cost epifluorescence apparatus, instead of the more expensive TIRF or confocal
microscopes, which would enable SM analysis to take place in most scientific
laboratories.
PMID- 29942375
TI - Turning the Page to Year 2016.
AB - As we conclude another year (2015), Volume 2 completed, we are pleased with the
number of quality published manuscripts. We are also excited to announce
Nanobiomedicine has been indexed in DOAJ (Directory of Open Access Journals)
(https://doaj.org/toc/1849-5435)! This was in part attributed with the help of
our Special Editor, Dr. Barbara Smith, who spearheaded manuscripts highlighting
innovative results that impacted the global health spectrum implementing new
methods for disease diagnosis, including technological and product development
for enhanced point-of-care and personalized health care. Dr. Smith undertook this
endeavor as she transitioned from a post-doc position (from George Whitesides'
lab at Harvard University) to a faculty position at Arizona State, getting
acclimated and setting up her laboratory. We want to thank Dr. Smith for her time
and commitment to our journal. It's worth noting, we had a high number of
submissions throughout the year, however, the expectations of the manuscripts not
published fell short due to our review process, indicating the emphasis of
publishing high quality manuscripts. We thank all the reviewers for their time
and feedback.
PMID- 29942374
TI - ELISA-like Analysis of Cisplatinated DNA Using Magnetic Separation.
AB - Cisplatin belongs to the most widely used cytostatic drugs. The determination of
the presence of the DNA-cisplatin adducts may not only signal the guanine-rich
regions but also monitor the interaction reaction between DNA and the drug in
terms of speed of interaction. In this work, the combined advantages of magnetic
particles-based isolation/purification with fluorescent properties of quantum
dots (QDs) and antibodies targeted on specific recognition of DNA-cisplatin
adducts are demonstrated. The formation of a complex between magnetic particles
with surface modified by anti-dsDNA antibody, cisplatin-modified DNA and QDs
labelled anti-cisplatin-modified DNA antibody was suggested and optimized.
PMID- 29942376
TI - Aminosilane Functionalization and Cytotoxicity Effects of Upconversion
Nanoparticles Y2O3 and Gd2O3 Co-Doped with Yb3+and Er3.
AB - In this study, luminescent upconversion nanoparticles (UCNPs) Y2O3 and Gd2O3 co
doped with Yb3+ and Er3+ were prepared by the sol-gel method (SG). These NPs are
able to absorb near infrared photons and upconvert them into visible radiation
with a direct application in bioimaging, as an important tool to diagnose and
visualize cancer cells. The UCNPs were coated with a thin silica shell and
functionalized with amino groups for further folic acid conjugation to allow
their interaction with folate ligands on the cell surface. Their physical
properties were analysed by Transmission Electron Microscopy (TEM), Fourier
transform infrared spectroscopy (FTIR) and photoluminescence (PL) measurements.
The PL results revealed excellent luminescence properties on all core-shell
UCNPs. Cytotoxicity experiments with concentrations of bare and aminosilane
coated/functionalized UCNPs between 0.001 MUg/mL to 1 MUg/mL were tested on two
different cell lines from human cervix carcinoma (HeLa) and human colorectal
adenocarcinoma (DLD-1) with a colorimetric assay based on the reduction of MTT
reagent (methy-134-thiazolyltetrazolium). The assays show that some
concentrations of bare UCNPs were cytotoxic for cervical adenocarcinoma cells
(HeLa); however, for human colorectal adenocarcinoma all UCNPs are non-cytotoxic.
After UCNPs functionalization with silica-aminosilane (APTES/TEOS), all of the
nanoparticles tested were found to be non-cytotoxic for both cell lines. The
UCNPs functionalized in this work can be further conjugated with specific ligands
and used as biolabels for detection of cancer cells.
PMID- 29942377
TI - Formyl-Peptide Receptor Agonists and Amorphous SiO2-NPs Synergistically and
Selectively Increase the Inflammatory Responses of Human Monocytes and PMNs.
AB - We tested whether amorphous SiO2-NPs and formylpeptide receptor (FPRs) agonists
synergistically activate human monocytes and neutrophil polymorphonuclear
granulocytes (PMNs). Peptide ligands specifically binding to FPR1 (f-MLP) and to
FPR2 (MMK-1, WKYMVM and WKYMVm) human isoforms did not modify the association of
SiO2-NPs to both cell types or their cytotoxic effects. Similarly, the extent of
CD80, CD86, CD83, ICAM-1 and MHCII expression in monocytes treated with SiO2-NPs
was not significantly altered by any FPRs agonist. However, FPR1 stimulation with
f-MLP strongly increased the secretion of IL-1beta, IL-6 and IL-8 by human
monocytes, and of IL-8 by PMNs in the presence of SiO2-NPs, due to the synergic
stimulation of gene transcription. FPR2 agonists also up-modulated the production
of IL-1beta induced by monocytes treated with SiO2-NPs. In turn, SiO2-NPs
increased the chemotaxis of PMNs toward FPR1-specific ligands, but not toward
FPR2-specific ones. Conversely, the chemotaxis of monocytes toward FPR2-specific
peptides was inhibited by SiO2-NPs. NADPH-oxidase activation triggered by FPR1-
and FPR2-specific ligands in both cell types was not altered by SiO2-NPs.
Microbial and tissue danger signals sensed by FPRs selectively amplified the
functional responses of monocytes and PMNS to SiO2-NPs, and should be carefully
considered in the assessment of the risk associated with nanoparticle exposure.
PMID- 29942378
TI - Gold Nanoparticles Impinge on Nucleoli and the Stress Response in MCF7 Breast
Cancer Cells.
AB - Cancer cells can take up gold nanoparticles of different morphologies. These
particles interact with the plasma membrane and often travel to intracellular
organelles. Among organelles, the nucleus is especially susceptible to the damage
that is inflicted by gold nanoparticles. Located inside the nucleus, nucleoli are
specialized compartments that transcribe ribosomal RNA genes, produce ribosomes
and function as cellular stress sensors. Nucleoli are particularly prone to gold
nanoparticle-induced injury. As such, small spherical gold nanoparticles and gold
nanoflowers interfere with the transcription of ribosomal DNA. However, the
underlying mechanisms are not fully understood. In this study, we examined the
effects of gold nanoparticles on nucleolar proteins that are critical to ribosome
biogenesis and other cellular functions. We show that B23/nucleophosmin, a
nucleolar protein that is tightly linked to cancer, is significantly affected by
gold nanoparticles. Furthermore, gold nanoparticles impinge on the cellular
stress response, as they reduce the abundance of the molecular chaperone hsp70
and O-GlcNAc modified proteins in the nucleus and nucleoli. Together, our studies
set the stage for the development of nanomedicines that target the nucleolus to
eradicate proliferating cancer cells.
PMID- 29942379
TI - Knock-down of ELMO1 in Paediatric Rhabdomyosarcoma Cells by Nanoparticle Mediated
siRNA Delivery.
AB - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma that is found in
children and has a poor outcome for those with metastatic disease. Two
histological groups have been distinguished - embryonal (ERMS) and alveolar
(ARMS) forms. The ARMS subtype has higher rates of metastasis, as well as higher
levels of ELMO1, which is thought to be involved in cell migration. Therefore,
the knock-down of ELMO1 by targeted siRNA could provide a mechanism to prevent
the metastatic behaviour of ARMS cells. However, challenges still lie in the
delivery of nucleotides to a tumour site. Herein, we have described the use of a
variety of mesoporous silica nanoparticles as a delivery system for siRNA that is
specific for ELMO1 and shown the effective reduction in cell invasive behaviour
in these cells.
PMID- 29942380
TI - saltPAD: A New Analytical Tool for Monitoring Salt Iodization in Low Resource
Settings.
AB - We created a paper test card that measures a common iodizing agent, iodate, in
salt. To test the analytical metrics, usability, and robustness of the paper test
card when it is used in low resource settings, the South African Medical Research
Council and GroundWork performed independent validation studies of the device.
The accuracy and precision metrics from both studies were comparable. In the
SAMRC study, more than 90% of the test results (n=1704) were correctly classified
as corresponding to adequately or inadequately iodized salt. The cards are
suitable for market and household surveys to determine whether salt is adequately
iodized. Further development of the cards will improve their utility for
monitoring salt iodization during production.
PMID- 29942381
TI - Designer DNA Architectures: Applications in Nanomedicine.
AB - DNA has been used as a material for the construction of nanoscale objects. These
nanostructures are programmable and allow the conjugation of biomolecular guests
to improve their functionality. DNA nanostructures display a wide variety of
characteristics, such as cellular permeability, biocompatibility and stability,
and responsiveness to external stimuli, making them excellent candidates for
applications in nanomedicine.
PMID- 29942382
TI - Global Health Innovation Technology Models.
AB - Chronic technology and business process disparities between High Income, Low
Middle Income and Low Income (HIC, LMIC, LIC) research collaborators directly
prevent the growth of sustainable Global Health innovation for infectious and
rare diseases. There is a need for an Open Source-Open Science Architecture
Framework to bridge this divide. We are proposing such a framework for
consideration by the Global Health community, by utilizing a hybrid approach of
integrating agnostic Open Source technology and healthcare interoperability
standards and Total Quality Management principles. We will validate this
architecture framework through our programme called Project Orchid. Project
Orchid is a conceptual Clinical Intelligence Exchange and Virtual Innovation
platform utilizing this approach to support clinical innovation efforts for multi
national collaboration that can be locally sustainable for LIC and LMIC research
cohorts. The goal is to enable LIC and LMIC research organizations to accelerate
their clinical trial process maturity in the field of drug discovery, population
health innovation initiatives and public domain knowledge networks. When
sponsored, this concept will be tested by 12 confirmed clinical research and
public health organizations in six countries. The potential impact of this
platform is reduced drug discovery and public health innovation lag time and
improved clinical trial interventions, due to reliable clinical intelligence and
bio-surveillance across all phases of the clinical innovation process.
PMID- 29942383
TI - Bioavailability of Orally Delivered Alpha-Tocopherol by Poly(Lactic-Co-Glycolic)
Acid (PLGA) Nanoparticles and Chitosan Covered PLGA Nanoparticles in F344 Rats.
AB - It is hypothesized that the bioavailability of alphaT (alpha-tocopherol), an
antioxidant, can be improved when delivered by poly(lactic-co-glycolic) acid
(PLGA) nanoparticles (NPs) and chitosan covered PLGA nanoparticles (PLGA-Chi
NPs), and that the mucoadhesive properties of chitosan may enhance absorption of
alphaT. PLGA and PLGA-Chi NPs were characterized by measuring entrapment
efficiency, size, polydispersity, and zeta potential. Nanoparticle physical
stability, chemical stability of entrapped alphaT, and release kinetics were also
measured. Pharmacokinetic studies were conducted by administering PLGA (alphaT)
NPs, PLGA-Chi (alphaT) NPs, and free alphaT via oral gavage in rats. The size and
zeta potential of the two particle systems were 97.87 +/- 2.63 nm and -36.2 +/-
1.31 mV for PLGA(alphaT) NPs, and 134 +/- 2.05 nm and 38.0 +/- 2.90 mV for PLGA
Chi (alphaT) nanoparticles in DI water. The particle systems showed to be stable
during various in vitro assays. Bioavailability of nanodelivered alphaT was
improved compared to the free alphaT, by 170% and 121% for PLGA and PLGA-Chi NPs,
respectively. It was concluded that while chitosan did not further improved
bioavailability of alphaT, PLGA NPs protected the entrapped drug from the GI
environment degradation and proved to be an effective delivery system for alphaT.
PMID- 29942384
TI - ZnO Nanoparticles: A Promising Anticancer Agent.
AB - Nanoparticles, with their selective targeting capabilities and superior efficacy,
are becoming increasingly important in modern cancer therapy and starting to
overshadow traditional cancer therapies such as chemotherapy radiation and
surgery. ZnO nanoparticles, with their unique properties such as
biocompatibility, high selectivity, enhanced cytotoxicity and easy synthesis, may
be a promising anticancer agent. Zinc, as one of the major trace elements of the
human body and co-factor of more than 300 mammalian enzymes, plays an important
role in maintaining crucial cellular processes including oxidative stress, DNA
replication, DNA repair, cell cycle progression and apoptosis. Thus, it is
evident that an alteration in zinc levels in cancer cells can cause a deleterious
effect. Research has shown that low zinc concentration in cells leads to the
initiation and progression of cancer and high zinc concentration shows toxic
effects. Zinc-mediated protein activity disequilibrium and oxidative stress
through reactive oxygen species (ROS) may be the probable mechanism of this
cytotoxic effect. The selective localization of ZnO nanoparticles towards cancer
cells due to enhanced permeability and retention (EPR) effect and electrostatic
interaction and selective cytotoxicity due to increased ROS present in cancer
cells show that ZnO nanoparticles can selectively target and kill cancer cells,
making them a promising anticancer agent.
PMID- 29942386
TI - Cross-presentation of lactoferrin encapsulated into chitosan-based nanoparticles.
AB - Induction of CD8+ cytotoxic T-cell response is essential for the protection from
intracellular pathogens. It requires major histocompatibility complex class I
processing of newly synthesized proteins transported from the cytosolic pathway.
Presentation of mature soluble proteins occurs via a cross-presentation (CP)
pathway that is much less efficient in the activation of cytotoxic response.
Encapsulation of proteins into polymeric nanoparticles (NPs) can modulate the
efficacy of antigen CP. In this article, a model antigen lactoferrin (L) was
encapsulated into polysaccharide NPs with different physicochemical properties
(size, charge, and hydrophobicity) and used as an immunogen. CD8+ or CD4+
associated IgG2a or IgG1 subclasses of L-specific antibodies, respectively,
served as a measure of CD8+ versus CD4+ T-cell activation. Among five types of
NPs produced, only succinylchitosan-galactomannan (LSG) and succinylchitosan-PEG
chitosan (LSPC) NPs induced a significant IgG2a response. IgG1 production was
comparable in all but hydrophobic succinyl-dodecyl-chitosan (LSD) NPs, where it
was only marginal. Confocal studies demonstrated that galactomannan-equipped LSG
NPs induced vacuolar type of CP, while positively charged LSPC-NPs were
transported mostly via the cytosolic CP pathway.
PMID- 29942387
TI - Microbubble-liposome conjugate: Payload evaluation of potential theranostic
vehicle.
AB - Liposome-microbubble conjugates are considered as better targeted drug delivery
vehicles compared to microbubbles alone. The microbubble in the integrated drug
delivery system delivers the drug intracellularly on the target, whereas the
liposome component allows loading of high drug dose and extravasation through
leaky vasculature. In this work, a new high yielding microbubble production
method was used to prepare microbubbles for formulation of the liposome
conjugated drug delivery system. In formulation process, the prepared liposome of
200 nm diameter was attached to the microbubble surface using the avidin-biotin
interaction. The analysis of the confocal scanning laser microscope images showed
that approximately 8 * 108 microbubbles per millilitre (range: 2-7 MUm, mean size
5 +/- 0.5 MUm) can be efficiently conjugated to the liposomes. The method of
conjugation was found to be effective in attaching liposome to microbubbles.
PMID- 29942388
TI - Development, in vitro and in vivo evaluations of novel lipid drug delivery system
of Newbouldia laevis (P. Beauv.).
AB - Newbouldia laevis (P. Beauv.) is a tropical rainforest plant used in traditional
folk medicine for the treatment of malaria, cough, joint pains, stomach ache,
oedema and inflammation. The main thrust of this research work was to study the
analgesic/anti-nociceptive properties of N. laevis-loaded solid lipid
microdispersions. N. laevis leaves were extracted using ethanol, and the extract
was formulated into solid lipid microdispersions using lipid matrix comprising a
rational blend of Precirol(r) ATO 5 and Softisan(r) 154. Characterization of the
solid lipid microdispersions include determination of morphology, particle size,
pH, thermal property, encapsulation efficiency percentage and analgesic/anti
nociceptive property. The results obtained showed that the particles were
spherical with sizes ranging from 40 um to 125 um. The solid lipid
microdispersions maintained a stable pH within the acidic region of 5-6 with
insignificant variations (p > 0.05) over a period of 90 days. Thermal analysis
showed that N. laevis was entrapped in the lipid matrix used for the
formulations. Solid lipid microdispersions recorded a maximum encapsulation
efficiency up to 88.1%. N. laevis-loaded solid lipid microdispersions also
produced good analgesic/anti-nociceptive property comparable with the standard
diclofenac potassium. N. laevis-loaded solid lipid microdispersions showed good
analgesic/anti-nociceptive effect and could be used in the treatment and
management of pain.
PMID- 29942385
TI - Nanobiosensors in diagnostics.
AB - Medical diagnosis has been greatly improved thanks to the development of new
techniques capable of performing very sensitive detection and quantifying certain
parameters. These parameters can be correlated with the presence of specific
molecules and their quantity. Unfortunately, these techniques are demanding,
expensive, and often complicated. On the other side, progress in other fields of
science and technology has contributed to the rapid growth of nanotechnology.
Although being an emerging discipline, nanotechnology has raised huge interest
and expectations. Most of the enthusiasm comes from new possibilities and
properties of nanomaterials. Biosensors (simple, robust, sensitive, cost
effective) combined with nanomaterials, also called nanobiosensors, are serving
as bridge between advanced detection/diagnostics and daily/routine tests. Here we
review some of the latest applications of nanobiosensors in diagnostics field.
PMID- 29942389
TI - Antitumor activity of tanshinone and its nanoparticles on U14 cervical carcinoma
bearing mice.
AB - In this study, tanshinone was extracted from Salvia miltiorrhiza. To improve the
utilization and the dissolution of the drug, the tanshinone extractions were
prepared at a pharmaceutical nanoscale and in the nanometer range of 100-200 nm.
Then, the rate of tumor inhibition and the activity of antioxidant system and the
thymus/spleen indices were investigated to find the antitumor effect of
nanoparticles of tanshinone in cervical carcinoma-bearing mice. Our data suggest
that tanshinone inhibits cervical tumor growth and the rates of tumor inhibition
of all drug groups were more than 45%. The highest rate was 70.88% in the high
dose of nanoscale tanshinone group. The activities of superoxide dismutase were
higher in drug groups than in the model control group, and the concentrations of
malondialdehyde were significantly lower. These findings suggested that
tanshinone enhance the superoxide dismutase activity of the mice and decrease the
malondialdehyde content. It may be one of the mechanisms of antitumor effect of
tanshinone. The thymus index and spleen index were higher than normal control or
model control. These data suggested that tanshinone also enhanced the immune
system of mice.
PMID- 29942390
TI - Modulation of the contractility of micropatterned myocardial cells with nanoscale
forces using atomic force microscopy.
AB - The ability to modulate cardiomyocyte contractility is important for
bioengineering applications ranging from heart disease treatments to biorobotics.
In this study, we examined the changes in contraction frequency of neonatal rat
cardiomyocytes upon single-cell-level nanoscale mechanical stimulation using
atomic force microscopy. To measure the response of same density of cells, they
were micropatterned into micropatches of fixed geometry. To examine the effect of
the substrate stiffness on the behavior of cells, they were cultured on a stiffer
and a softer surface, glass and poly (dimethylsiloxane), respectively. Upon
periodic cyclic stimulation of 300 nN at 5 Hz, a significant reduction in the
rate of synchronous contraction of the cell patches on poly(dimethylsiloxane)
substrates was observed with respect to their spontaneous beat rate, while the
cell patches on glass substrates maintained or increased their contraction rate
after the stimulation. On the other hand, single cells mostly maintained their
contraction rate and could only withstand a lower magnitude of forces compared to
micropatterned cell patches. This study reveals that the contraction behavior of
cardiomyocytes can be modulated mechanically through cyclic nanomechanical
stimulation, and the degree and mode of this modulation depend on the cell
connectivity and substrate mechanical properties.
PMID- 29942391
TI - Improving health-care delivery in low-resource settings with nanotechnology:
Challenges in multiple dimensions.
AB - In the two decades after 1990, the rates of child and maternal mortality dropped
by over 40% and 47%, respectively. Despite these improvements, which are in part
due to increased access to medical technologies, profound health disparities
exist. In 2015, a child born in a developing region is nearly eight times as
likely to die before the age of 5 than one born in a developed region and
developing regions accounted for nearly 99% of the maternal deaths. Recent
developments in nanotechnology, however, have great potential to ameliorate these
and other health disparities by providing new cost-effective solutions for
diagnosis or treatment of a variety of medical conditions. Affordability is only
one of the several challenges that will need to be met to translate new ideas
into a medical product that addresses a global health need. This article aims to
describe some of the other challenges that will be faced by nanotechnologists who
seek to make an impact in low-resource settings across the globe.
PMID- 29942392
TI - Hepatocyte-based flow analytical bioreactor for online xenobiotics metabolism
bioprediction.
AB - The research for new in vitro screening tools for predictive metabolic profiling
of drug candidates is of major interest in the pharmaceutical field. The main
motivation is to avoid late rejection in drug development and to deliver safer
drugs to the market. Thanks to the superparamagnetic properties of iron oxide
nanoparticles, a flow bioreactor has been developed which is able to perform
xenobiotic metabolism studies. The selected cell line (HepaRG) maintained its
metabolic competencies once iron oxide nanoparticles were internalized. Based on
magnetically trapped cells in a homemade immobilization chamber, through which a
flow of circulating phase was injected to transport nutrients and/or the studied
xenobiotic, off-line and online (when coupled to a high-performance liquid
chromatography chain) metabolic assays were developed using diclofenac as a
reference compound. The diclofenac demonstrated a similar metabolization profile
chromatogram, both with the newly developed setup and with the control situation.
Highly versatile, this pioneering and innovative instrumental design paves the
way for a new approach in predictive metabolism studies.
PMID- 29942394
TI - Heterogeneity Does Matter for Tumor Characterization.
PMID- 29942393
TI - Cytotoxicity assessment, inflammatory properties, and cellular uptake of
Neutraplex lipid-based nanoparticles in THP-1 monocyte-derived macrophages.
AB - Current antiretroviral drugs used to prevent or treat human immunodeficiency
virus type 1 (HIV-1) infection are not able to eliminate the virus within tissues
or cells where HIV establishes reservoirs. Hence, there is an urgent need to
develop targeted delivery systems to enhance drug concentrations in these viral
sanctuary sites. Macrophages are key players in HIV infection and contribute
significantly to the cellular reservoirs of HIV because the virus can survive for
prolonged periods in these cells. In the present work, we investigated the
potential of the lipid-based Neutraplex nanosystem to deliver anti-HIV
therapeutics in human macrophages using the human monocyte/macrophage cell line
THP-1. Neutraplex nanoparticles as well as cationic and anionic Neutraplex
nanolipoplexes (Neutraplex/small interfering RNA) were prepared and characterized
by dynamic light scattering. Neutraplex nanoparticles showed low cytotoxicity in
CellTiter-Blue reduction and lactate dehydrogenase release assays and were not
found to have pro-inflammatory effects. In addition, confocal studies showed that
the Neutraplex nanoparticles and nanolipoplexes are rapidly internalized into THP
1 macrophages and that they can escape the late endosome/lysosome compartment
allowing the delivery of small interfering RNAs in the cytoplasm. Furthermore,
HIV replication was inhibited in the in vitro TZM-bl infectivity assay when small
interfering RNAs targeting CXCR4 co-receptor was delivered by Neutraplex
nanoparticles compared to a random small interfering RNA sequence. This study
demonstrates that the Neutraplex nanosystem has potential for further development
as a delivery strategy to efficiently and safely enhance the transport of
therapeutic molecules into human monocyte-derived macrophages in the aim of
targeting HIV-1 in this cellular reservoir.
PMID- 29942395
TI - Contribution of Radionuclide Theranostics for Managing Intractable Malignancies.
PMID- 29942397
TI - Peptide Receptor Radionuclide Therapy and the Treatment of Gastroentero
pancreatic Neuroendocrine Tumors: Current Findings and Future Perspectives.
AB - Purpose and Methods: Patients with inoperable and metastasized neuroendocrine
tumors (NETs), particularly those with grades 1 and 2, usually receive treatment
with somatostatin analogues (SSAs). Peptide receptor radionuclide therapy (PRRT)
has gained momentum over the past two decades in patients who progress on SSAs.
177Lu-DOTATATE is currently the most widely used radiopeptide for PRRT. We
reviewed the recent evidence on PRRT and the treatment of gastroentero-pancreatic
neuroendocrine tumors (GEP-NETs). Results: 177Lu-DOTATATE can be used as
neoadjuvant treatment in patients with inoperable GEP-NETs, who might be
candidate for surgery after treatment and as adjuvant therapy after surgical
intervention. Combination treatments of PRRT with chemotherapy or targeted agents
as well as combinations of radionuclides in patients with NETs have been explored
over the last few years. The majority of patients with NETs experience partial
response or have disease stabilization, a small percentage has complete response,
while some 30% of patients, however, will have disease progression. The safety
and efficacy of retreatment with extra cycles of PRRT as salvage therapy have
been evaluated in small retrospective series. Conclusion: Overall, there is
evidence that disease control and quality of life improve significantly after
117Lu PRRT therapy. Clinical trials on this therapy are scarce, and there is a
need for further studies to establish proper management guidelines.
PMID- 29942396
TI - Radiomics in Oncological PET/CT: Clinical Applications.
AB - 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
(PET/CT) is widely used for staging, evaluating treatment response, and
predicting prognosis in malignant diseases. FDG uptake and volumetric PET
parameters such as metabolic tumor volume have been used and are still used as
conventional PET parameters to assess biological characteristics of tumors.
However, in recent years, additional features derived from PET images by
computational processing have been found to reflect intratumoral heterogeneity,
which is related to biological tumor features, and to provide additional
predictive and prognostic information, which leads to the concept of radiomics.
In this review, we focus on recent clinical studies of malignant diseases that
investigated intratumoral heterogeneity on PET/CT, and we discuss its clinical
role in various cancers.
PMID- 29942398
TI - Treatment of Bone Metastasis with Bone-Targeting Radiopharmaceuticals.
AB - Bone is a common metastatic site of cancer. Bone metastasis reduces life
expectancy and results in serious symptoms and complications such as bone pain,
pathological fractures, and spinal cord compression, decreasing quality of life
by restricting sleep and mobility. Treatment for bone metastasis includes drugs
(pure analgesics, hormones, cytotoxic chemotherapy, and bisphosphonates, among
others), external radiation therapy, surgery, and radionuclide therapy using bone
targeting radiopharmaceuticals. Particulate radiation with alpha- or beta-rays is
used as a bone-targeting radiopharmaceutical in radionuclide therapy. beta
Emitters have lower energy and a longer range than alpha-emitters and have less
tumoricidal activity and deliver more radiation to adjacent normal tissue.
Therefore, the main therapeutic effect of bone-targeting beta-emitters such as
89Sr-dichloride is bone pain palliation rather than enhanced survival. In
contrast, alpha-emitters such as 223Ra-dichloride have high energy and a short
range, resulting in greater tumoricidal activity and less radiation damage to
adjacent normal tissue. Treatment with bone-targeting alpha-emitters can improve
survival and decrease bone pain. This review focuses on the principles and
clinical utility of several clinically available bone-targeting
radiopharmaceuticals in metastatic bone disease.
PMID- 29942399
TI - Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine
Tumors.
AB - Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation
therapy using a compound of beta-emitting radionuclide chelated to a peptide for
the treatment of tumor with overexpressed specific cell receptor such as
somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical
resection should be performed for the curative treatment for NETs when it is
feasible; however, a multi-disciplinary approach is needed when locally advanced
or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin
analogues, as a new treatment modality targeting metastatic or inoperable NETs
expressing the SSTR2, have been developed and successfully used for the past two
decades. As Lu-177 emits both beta- and gamma-radiation, it has the ability as a
theragnostic agent for NETs compared with only beta-emitting yttrium-90 labeled
PRRT. Several recent studies reported that Lu-177 gave an overall positive
response and improved the patients' quality of life. To fully exploit its
potential, large comparative studies are needed for the assessment of distinct
efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications
and developing new regimens of Lu-177-based PRRT, more dedicated clinical
research is required.
PMID- 29942400
TI - Evaluating the Predictive Ability of Initial Staging F-18 FDG PET/CT for the
Prognosis of Non-Hodgkin Malignant Lymphoma Patients Who Underwent Stem Cell
Transplantation.
AB - Objectives: This study aimed to determine the value of clinical prognostic
factors and semiquantitative metabolic parameters from initial staging fluorine
18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG
PET/CT) in non-Hodgkin lymphoma (NHL) patients treated with stem cell
transplantation (SCT). Methods: A total of 39 malignant lymphoma patients who
underwent initial staging F-18 FDG PET/CT were enrolled in this study. SUVmax,
MTV_wb, and TLG_wb were measured during the initial staging PET/CT. Receiver
operating characteristic curve (ROC) analysis was adopted to dichotomize
continuous variables. Log-rank test and Cox proportional hazard regression
analysis were used to evaluate disease-free survival (DFS) rate. Results: Among
the 39 patients with malignant lymphoma, 17 (43.6%) had a relapse. For several
clinical factors such as age, ECOG performance score, AMC/ALC score, stages, and
revised International Prognostic Index score, differences between the two
dichotomized groups were statistically insignificant. In univariate analysis, DFS
estimates were 71.0 +/- 7.8 months and 18.0 +/- 5.9 months in high-SUVmax and low
SUVmax group, respectively (P < 0.01). For MTV_wb, DFS estimates were 46.6 +/-
12.4 months and 69.1 +/- 8.5 months in high-MTV_wb and low-MTV_wb group,
respectively (P = 0.12). For TLG_wb, DFS estimates were 65.3 +/- 7.5 months and
13.7 +/- 8.6 months in high-TLG_wb and low-TLG_wb group, respectively (P = 0.02).
In Cox proportional hazard regression analysis, only MTV_wb showed statistical
significance (HR 3.01, 95% CI 1.04-8.74, P = 0.04). Conclusion: In NHL patients
treated with SCT, the MTV_wb of initial staging F-18 FDG PET/CT was an
independent prognostic factor.
PMID- 29942401
TI - A Single Intraperitoneal Injection of Endotoxin Changes Glial Cells in Rats as
Revealed by Positron Emission Tomography Using [11C]PK11195.
AB - Purpose: Intracranial administration of lipopolysaccharide (LPS) is known to
elicit a rapid innate immune response, activate glial cells in the brain, and
induce depression-like behavior. However, no study has focused on the changes in
glial cells induced by intraperitoneal injection of LPS in vivo. Methods: Ten
adult male Fischer F344 rats underwent [11C]PK11195 PET before and 2 days after
intraperitoneal injection of LPS to evaluate the changes in glial cells. The
difference in standardized uptake values (SUV) of [11C]PK11195 between before and
after injection was determined. Results: There was a cluster of brain regions
that showed significant reductions in SUV. This cluster included the bilateral
striata and bilateral frontal regions, especially the somatosensory areas.
Conclusions: Changes in activity of glial cells induced by the intraperitoneal
injection of LPS were detected in vivo by [11C]PK11195 PET. Intraperitoneal
injection of LPS is known to induce depression, and further studies with
[11C]PK11195 PET would clarify the relationships between neuroinflammation and
depression.
PMID- 29942402
TI - Analysis of Iodine Content in Salts and Korean Sauces for Low-Iodine Diet
Education in Korean Patients with Thyroid Cancer Preparing for Radioiodine
Therapy.
AB - Purpose: A low-iodine diet is necessary in patients about to undergo radioiodine
therapy for thyroid cancer to decrease the competitive absorption of ingested
nonradioactive iodine. This study aimed to assess the iodine concentrations in
salts and basic Korean sauces, and to provide fundamental data for guidelines on
a low-iodine diet before radioiodine therapy. Methods: The iodine contents of
refined salts, solar sea salts, fish sauces, and commonly used Korean sauces with
added refined salt were determined by ICP-MS. Results: The iodine content of
refined salts was found to be very low (0.033 +/- 0.05 MUg/100 g) compared with
that of solar sea salts (434 +/- 73.6 MUg/100 g). The iodine contents of Korean
soy sauce, Korean soybean paste, Gochujang seasoned with refined salt were also
very low (0.010, 0.044, 0.002 MUg/100 g, respectively). However, the mean iodine
contents of the shrimp and fish Jeots analyzed in this study were found to be
41.3 +/- 4.2 and 24.8 +/- 4.5 MUg/100 g, respectively. Conclusion: This study is
the first to investigate the iodine contents of the salts and basic sauces used
in Korea. The results show that refined salts and Korean traditional sauces
seasoned with them can be safely used in low-iodine diets before radioiodine
therapy.
PMID- 29942403
TI - Survey Result of the Counting Efficiency of Gamma Counter by Certified Reference
Materials.
AB - Purpose: In radioimmunoassay (RIA), the gamma counter is the important instrument
for the accurate measurement. To manage quality assurance of RIA, the counting
efficiency of gamma counter is one of the important parameters. The aim of this
study was to evaluate the counting efficiency of gamma counters in multiple
institutes on the base of traceability by using the certified reference materials
(CRMs). Methods: Twenty-three institutes that perform RIA were enrolled in this
study. I-125 CRMs that were certified by National Institute of Standards and
Technology (NIST) were used. Each institute was asked to count the activity of I
125 CRMs at most twice on all gamma counters in use. The counting efficiency of
each well of counter was calculated on the base of NIST-certified information,
corrected for I-125 decay for date of testing. Results: From 23 institutes, 44
gamma counters were evaluated. The average counting efficiency of all wells was
85.9% and the standard deviation was 13.5%. As a mean value of each gamma
counter, three gamma counters showed poor counting efficiency (less than 70%).
The poorest counting efficiency was 7%. The counting efficiency of seven gamma
counters was between 70 and 75%. Eight counters had the counting efficiency
between 75 and 90%. More than half of counter (26 gamma counters) showed
excellent counting efficiency (more than 90%). The standard deviation variation
range of inter-well efficiency was from 0 to 11.2. Conclusion: The first survey
on the counting efficiency of gamma counter was performed in South Korea. Most of
the RIA laboratories have well managed the quality assurance of gamma counter.
PMID- 29942404
TI - Incidental Detection of Parathyroid Adenoma on Somatostatin Receptor PET/CT and
Incremental Role of 18F-Fluorocholine PET/CT in MEN1 Syndrome.
AB - Multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by combined
occurrence of tumors of endocrine glands including the parathyroid, the
pancreatic islet cells, and the anterior pituitary gland. Parathyroid involvement
is the most common manifestation and usually the first clinical involvement in
MEN1 syndrome, followed by gastroentero-pancreatic neuroendocrine tumors (NETs).
Here we present a case where the patient initially presented with metastatic
gastric NET and a single parathyroid adenoma was detected incidentally on 68Ga
DOTANOC PET/CT done as part of post 177Lu-DOTATATE therapy (PRRT) follow-up.
Further 18F-fluorocholine PET/CT showed four adenomas for which the patient
subsequently underwent subtotal parathyroidectomy.
PMID- 29942405
TI - Incidental Detection of Peri-Renal Hemorrhage on F-18 FDG PET/CT Imaging in a
Patient with Polycystic Kidney Disease.
AB - A 72-year-old male patient with a history of polycystic kidney disease and lung
malignancy underwent F-18 fluorodeoxyglucose positron emission
tomography/computed tomography (FDG PET/CT) for the evaluation of tumor
recurrence. The FDG PET/CT and subsequent non-enhanced CT scans revealed a
hemorrhage in the peri-renal space of the left original kidney. Interesting in
this case was the incidental detection of unexpected peri-renal hemorrhage during
an oncologic assessment with FDG PET/CT.
PMID- 29942406
TI - [Perinatal varicella: fetal and neonatal risks and management].
AB - The occurrence of clinical varicella during pregnancy is rare but it may pose
maternal and fetal risks. Perinatal maternal varicella may result in potentially
severe neonatal varicella, especially when maternal eruptions occur between 5
days before and 2 days after delivery. We report eight cases of newborns of
mothers with varicella in the peri-partum period in order to synthesize the
current state of knowledge on the risk of contracting virus as well as to develop
treatment protocol. We conducted a descriptive study at the Maternity and
Neonatology Center, Sousse, over a period of 10 years. Eight newborns were
included in the study. Prenatal diagnosis was made in 7 mothers. Only a woman
developed varicella 3 days after delivery. Five newborns were symptomatic on
admission. All newborns had typical varicella skin lesions, three of them had
respiratory distress associated. Treatment was based on newborn isolation, local
skin care and Acyclovir therapy. Patients evolution was favorable. The occurrence
of varicella infection during pregnancy remains possible in the countries where
vaccination is still not accessible to all. The risk of maternal and fetal
complications justifies specific and well codified treatment.
PMID- 29942407
TI - Socio-demographic determinants of malnutrition among primary school aged children
in Enugu, Nigeria.
AB - Introduction: Several factors including the parental literacy, illness,
socioeconomic status, poor sanitation and hygienic practices affect the physical
growth of children. The aim of this study was to determine the socio-demographic
determinants of malnutrition among primary school aged children in Enugu,
Nigeria. Methods: A cross-sectional descriptive study involving primary school
children in Enugu was carried out over a 3 month period. Subjects were selected
using multistage sampling technique. Weight and height were measured using a
digital scale and a wooden stadiometer, respectively. Body Mass Index (BMI),
weight-for-age (WAZ), Height-for-age (HAZ) and BMI-for-age z scores were then
derived using the new WHO reference standards. Results: 348 children (40.4%) were
recruited from 5 public schools while 512 (59.6%) were recruited from 9 private
schools. The mean age of the study participants was 9.2 +/- 1.8 years. 7 (0.8%)
children were stunted, 26 (3.3%) wasted and 28 (3.3%) underweight. Of all the
study participants, overweight and obesity were observed in 73 (8.5%) and 35
(4.1%) children, respectively. Children of lower socioeconomic class were more
stunted, underweight and wasted, while overweight and obesity were more prevalent
among children from the upper socioeconomic class. Conclusion: Factors such as
age and sex, parental education and socioeconomic class had a significant impact
on nutritional status. Overweight and obesity were more prevalent among the
children from the upper socioeconomic class, attending private schools, while
stunting and wasting were more in children of the lower class attending public
schools.
PMID- 29942408
TI - [Quality of the information system and of the effectiveness of public health
interventions in the areas in Benin experiencing performance-based financing
approach in 2014].
AB - Introduction: Performance-based financing (PBF) approach is a public health
intervention, whose effects on the pillars of this system are often not measured,
especially with regard to the information system and to the effectiveness of
public health interventions. Methods: Our cross-sectional study was conducted in
Benin in 67 health units randomly drawn from two PBF_HSS (Health Systems
Strengthening) health zones and two PBF_NHSSP (Health Sector Support Program)
areas, all experiencing PBF, and from two areas where the PBF had not been
implemented. It allowed to evaluate the quality of the information and the
effectiveness of public health interventions. The quality index and the
performance scores of the system components were used to compare the strata
covered by the PBF and the noncovered strata. Results: The quality of the
information system and of the effectiveness of public health interventions was
average in the three strata, with a higher quality index in the PBF_HSS (77%) and
PBF_NHSSP (74%) strata than in the Non_PBF (67%) strata. Health system quality
distribution was more favorable in the strata covered by PBF. The components
achieving a good performance were "demographic information", "results and
essential analyzes" and "statistic support archiving". However, the essential
components of the PBF and of the information system were "supervision" and
"reporting" that continued to have an average QI two years after the beginning of
the intervention. Conclusion: The average quality of the information system and
of the effectiveness of public health interventions could be improved by
respecting the instructions of the PBF, especially when the quality of this
system becomes a priority for the PBF.
PMID- 29942409
TI - [Hypereosinophilic syndrome associated with cardiac involvement].
AB - We report the case of a 30-year old man with no previous medical history and
without cardiovascular risk factors, hospitalized for NYHA Class IV dyspnoea
associated with palpitations in the Department of Cardiology. Clinical
examination showed signs of cardiac decompensation. The patient didn't have
fever, hepatosplenomegaly and palpable lymphadenopathies. Laboratory tests showed
hypereosinophilia greater than 4000 eosinophils per cubic millimeter.
Electrocardiogram objectified atrial tachycardia at a rate of 100 beats per
minute. Echocardiographic examination showed good left ventricular function,
dilation of both atria and a thrombus filling the right ventricular apex. The
diagnosis of thrombus lining the ventricular apex was suspected (A, B);
successive exams showed progressive filling of the right ventricular apex.
Cardiac MRI showed apical filling of both ventricles and after intravenous
injection of gadolinium, late subendocardial enhancement in the left ventricular
apex and in the right ventricular apex, suggesting fibrosis (C, D). Etiologic
investigation of hypereosinophilia excluded parasitic diseases, drug therapies,
neoplasias and autoimmune diseases as a cause. The diagnosis of idiopathic
hypereosinophilic syndrome associated with cardiac involvement was retained.
Corticosteroid therapy associated with hydroxyurea therapy and long-term
anticoagulant therapy were started. Patient's evolution was gradually favorable
with disappearance of hypereosinophilia.
PMID- 29942410
TI - The impetus to Africa CDC's mandate in curbing the rising trend of Antimicrobial
Resistance (AMR) in Africa: the launch of the Africa CDC AMR surveillance network
during the 8th advanced course in diagnostics (ACDx).
AB - The rise of antimicrobial resistance is a global threat and Africa like any other
developing setting is heavily affected. As one of its missions, the Africa CDC is
poised to ensure this rising trend takes a diminishing route in the few years
ahead. Diagnostics obviously play a pivotal role in AMR control and the advanced
course in diagnostics (ACDx) has been instrumental in training critical decision
makers over the past 7 years. This commentary presents an analysis of discussions
and exchanges during the launch of the Africa CDC AMR surveillance network at the
ACDX and the way forward for its implementation. The diagnostics priorities are
also highlighted.
PMID- 29942411
TI - [Legal redress in relation to physical injury due to post-traumatic anterior
pituitary insufficiency].
AB - Post-traumatic anterior pituitary insufficiency (PTAPI) is a rare but established
disease caused by ischemic lesions after severe cranial trauma. This case study
aims to highlight the criteria for imputability of PTAPI to a cranial trauma as
well as the specific principles of legal redress in relation to this disease. We
conducted a forensic study of a patient with diagnosed PTAPI followed up in the
Division of Endocrinology and Legal Medicine at the University Hospital, Sousse
(Tunisia). The patient included in the study was a 45-year old woman with no
particular past medical history. (6 gynaecological procedures, 4 parities and 2
abortions) having regular menstrual cycles, without a history of hemorrhagic
childbirth, who had been involved in a road accident (pedestrian got hit by a
car) causing occipital trauma without initial knowledge loss. She developed
hypothyroidism three years after the accident. The hormonal assessment showed the
involvement of all the other axes. Neuroradiological examination objectified
pituitary gland and pituitary stalk integrity. The definitive diagnosis of PTAPI
was made. Medical examination (performed 4 years after the accident) concluded
that PTAPI was imputable to the accident. Permanent partial disability rate
according to ordinary law has been assessed at 25%. PTAPI diagnosis is made by
elimination. The evaluation of physical injury should be based on residual
symptoms, on therapeutic constraints and on its impact on daily and professional
activity. Patient's evolution under hormone replacement therapy is often
favorable, however, complications may occur, hence the necessity to establish
these complications in order to preserve the right of the patient to underwent
new treatments.
PMID- 29942412
TI - Intra-colic textilome.
PMID- 29942413
TI - Level and pattern of human rabies and dog bites in Techiman Municipality in the
Middle Belt of Ghana: a six year retrospective records review.
AB - Introduction: Rabies is a viral zoonotic disease that is transmitted primarily by
bites from rabid dogs and has the highest case fatality rate of most infectious
diseases in humans. We described a 6-year trend of rabies and dog bites in a peri
urban district in Ghana. Methods: A record review was conducted in the health
facilities in Techiman to identify all human rabies and dog bite cases reported
from January 2011 to December 2016. Rabies and dog bite data were extracted from
health facilities records. Vaccination status of implicated dogs was extracted
from the veterinary records at the Techiman Disease Investigation Farm. Data were
summarized using proportions and presented using tables, charts and figures.
Results: Thirteen (13) cases of human rabies were recorded from 2011 to 2016.
Complete data was available for 10 cases. Median age of rabies victims was 30
(range 3-80 years). A majority were males (8 representing 61.5%). Eight cases
came from rural farming communities, 8 had a previous history of dog bite ranging
from two weeks to five months before the onset of rabies symptoms and one
reported with non-bite rabies. Case fatality was 100%. A total of 680 dog bites
were reported by health facilities. About 50.3% (342) of the victims were males,
a majority of bites (47.9%) occurred among children aged 1-15 years. Positive
rabies cases among offending dogs ranged from 3.3% in 2016 to 17.6% in 2014.
Conclusion: Mass vaccination of dogs and provision of post-exposure vaccination
are needed to reduce rabies transmission.
PMID- 29942415
TI - Intercostal leiomyoma in a child: review of the literature.
AB - Leiomyomas of the chest wall are very rare. In a review of the current literature
twelve cases were found, of which only one concerns of an intercostal leiomyoma
of the chest wall. We report a case of 1 year old male child with intercostal
leiomyoma who presented with a painless rigid swelling of the right chest wall.
The radiological control revealed a solid mass in the right anterior sixth
intercostal space. En-bloc excision of the mass by abrading of the sixth rib
through right anterior thoracotomy was performed. Histopatological analysis
showed a localized intercostal leiomyoma. The patient has a close follow-up for 6
months without evidence of recurrence. This is the first case of a primary
intercostal leiomyoma in a child which was excised totally without reconstruction
of the chest wall.
PMID- 29942414
TI - Prevalence of obesity, diabetes mellitus, hypertension and associated risk
factors in a mining workforce, Democratic Republic of Congo.
AB - Introduction: The burden of non-communicable diseases (NCDs) is increasing in low
and middle-income countries (LMIC). According to the World Health Organization
(WHO) the largest increase occurs in Africa. Obesity, diabetes mellitus and
hypertension (ODH) are major risk factors for cardiovascular diseases, causing
nearly 18 million deaths worldwide. Various risks associated with mining as an
occupational activity are implicated in NCDs' occurrence. This study describes
the baseline prevalence of ODH and associated risk factors in the workforce of
Tenke Fungurume Mining (TFM), in southern Democratic Republic of Congo. Methods:
A cross-sectional study was conducted on a sample of 2,749 employees' and
contractor's occupational health examination files for 2010. Socio-demographic,
occupational, medical, anthropometric and behavioral characteristics were
collected and assessed. Disease status regards ODH was based on WHO criteria. A
multivariate logistic regression model was used. Results: Overall prevalence of
ODH was 4.5%, 11.7%, and 18.2% respectively. Proportions of pre-ODH individuals
were 19.7%, 16.5%, and 47.8% respectively. Prevalence of ODH increased with age,
professional grade, nature of work, gender and reported alcohol use. Smoking 10
or more cigarettes per day increased risk of diabetes and hypertension, while
decreasing obesity. Conclusion: Rates of ODH and associated risk factors are
higher in the TFM workforce, than in the general DRC population. This is likely
reflective of other mining sites in the country and region. It is evident that
ODH are associated with various socio-demographic, occupational, anthropometric,
biomedical and behavioral risk factors. A NCD prevention program and close
monitoring of disease and risk factors trends are needed in this population.
PMID- 29942416
TI - Burden of care amongst caregivers who are first degree relatives of patients with
schizophrenia.
AB - Introduction: Caring for a mentally ill family member is a challenging task.
Caregivers who are first-degree relatives (FDR) are at a higher risk of
experiencing the negative consequences of caregiving. This study was aimed at
determining burden of care and its correlates in caregivers who are first-degree
relatives of patients with schizophrenia. Methods: A dyad of 255 patients and
caregivers was recruited. A socio-demographic questionnaire was administered to
both. The GHQ-12 was used to screen for psychiatric morbidity in the FDRs.
Caregiver's burden was assessed with the Zarit Burden Interview. Patients'
illness severity and level of functioning were assessed using the Brief
Psychiatric Rating Scale and the Global Assessment of Functioning scales
respectively. Results: The mean +/- SD age of caregivers and patients were 45.1
+/-12.3 and 36.7 +/-13.4 years respectively. About 49% of caregivers experienced
high burden of care. Older caregiver's age (r = 0.179; p < 0.004) and greater
illness severity (r = 0.332; p < 0.0001) in the patient had weak to moderate
positive correlation with burden of care. Caregiver's burden also increased with
poorer functioning of the patient (r = -0.467 p < 0.0001). Independent predictors
of caregiver burden were low level of education of the caregiver (OR 2.45; 95% CI
1.27-4.73), psychiatric morbidity in the caregiver (OR 6.74; 95% CI 2.51-18.15)
and poor patient functioning (OR 2.81; 95% CI 1.27-6.18). Conclusion: Caregivers
who are first-degree relatives of patients with schizophrenia experience varying
degrees of burden of care during caregiving. Routine screening and early
psychological intervention would help to ameliorate these negative consequences
of caregiving.
PMID- 29942417
TI - The impact of an unknown HIV serostatus on inpatient mortality.
AB - Introduction: Determining HIV serostatus is crucial for linking HIV-infected
patients to appropriate care, which might reduce their risk of subsequent
morbidity and mortality. A recent South African study demonstrated a potentially
harmful association between an unknown HIV serostatus and rehospitalisation. The
impact of an unknown HIV status on inpatient mortality has not yet been
established in that setting, which formed the impetus for the current study.
Methods: This was an unmatched case-control analysis of adult patient data
collected as part of a demographic survey at the Hlabisa Hospital, South Africa
between October 2009 and February 2014. Cases were defined as patients who
suffered inpatient mortality, while controls were patients who did not suffer
inpatient mortality. A sample size of 92 cases and 276 controls was used in this
study. Patient data related to age, gender, distance between referral clinic and
the hospital, HIV serostatus (HIV-negative, HIV-positive or an unknown HIV
serostatus) and comorbidity were analysed using recommended methods for unmatched
case-control studies. Results: When potential confounders were accounted for, we
found an unknown HIV serostatus to be associated with an almost 8-fold increase
in the odds of inpatient mortality when compared with patients who were known HIV
negative (Odds Ratio: 7.64, 95% Confidence Interval: 1.11-52.33, p = 0.038).
Conclusion: An unknown HIV serostatus was independently associated with a higher
odds of inpatient mortality. This finding highlights the potential benefit of
adopting an "opt-out" approach to HIV counseling and testing. Further research on
this topic is required.
PMID- 29942418
TI - [Fanconi anemia at the University Hospital (CHU) Hassan II of Fez: about 6
cases].
AB - Fanconi anemia is a recessive disorder associated with chromosomal instability.
It is marked by phenotypical heterogeneity which includes medullary deficiency, a
variable malformation syndrome, a predisposition to develop acute leukaemias
myeloides (ALM) and a cellular over-sensitiveness with the agents bridging the
ADN. The diagnosis is based on the abnormal increase in the rate of spontaneous
breaks chromosomal but especially and in a specific way, on a clear increase in
these chromosomal breaks in the presence of bifunctional alkylating agents, which
is the case in our six patients. Genetic counseling is that available for
autosomal recessive diseases. We report our initial observations conducted at the
University Hospital (CHU) Hassan II of Fez confirmed by the detection of a large
chromosomal instability after culture with Mitomycin C compared to a normal
control group. The purpose of this study was to update our knowledge of Fanconi
anemia genes and to highlight the role of cytogenetics in its diagnosis and the
genetic counseling for better management of affected children and their families.
PMID- 29942419
TI - Computational methods for birth-death processes.
AB - Many important stochastic counting models can be written as general birth-death
processes (BDPs). BDPs are continuous-time Markov chains on the non-negative
integers in which only jumps to adjacent states are allowed. BDPs can be used to
easily parameterize a rich variety of probability distributions on the non
negative integers, and straightforward conditions guarantee that these
distributions are proper. BDPs also provide a mechanistic interpretation - birth
and death of actual particles or organisms - that has proven useful in evolution,
ecology, physics, and chemistry. Although the theoretical properties of general
BDPs are well understood, traditionally statistical work on BDPs has been limited
to the simple linear (Kendall) process. Aside from a few simple cases, it remains
impossible to find analytic expressions for the likelihood of a discretely
observed BDP, and computational difficulties have hindered development of tools
for statistical inference. But the gap between BDP theory and practical methods
for estimation has narrowed in recent years. There are now robust methods for
evaluating likelihoods for realizations of BDPs: finite-time transition, first
passage, equilibrium probabilities, and distributions of summary statistics that
arise commonly in applications. Recent work has also exploited the connection
between continuously- and discretely-observed BDPs to derive EM algorithms for
maximum likelihood estimation. Likelihood-based inference for previously
intractable BDPs is much easier than previously thought and regression approaches
analogous to Poisson regression are straightforward to derive. In this review, we
outline the basic mathematical theory for BDPs and demonstrate new tools for
statistical inference using data from BDPs.
PMID- 29942420
TI - Distensibility and Gross Elasticity of the Skin at Various Body Sites and
Association with Pathological Scarring: A Case Study.
AB - Objective: Pathological scars, including hypertrophic scars and keloids, have a
strong predilection for specific regions of the body. Such site specificity might
reflect regional differences in skin properties. Greater knowledge about the
characteristics of the skin at various body regions can promote the development
of clinical approaches to skin incision and flap design and reduce the formation
of cutaneous scars. It could also help elucidate the etiology of pathological
scar development and progression. Thus, we measured the distensibility and gross
elasticity of the skin at various body sites. Methods: Five healthy adult
volunteers were enrolled. In each, the cutaneous viscoelasticity at 16 sites
(forehead, superior eyelid, lower jaw, earlobe, deltoid, outside and medial side
of the upper arm, palm, scapular region, anterior chest, upper abdomen, lateral
abdomen, lower abdomen, lateral thigh, anterior lower leg, and planta) was
examined using a Cutometer MPA 580(r) (Courage Khazaka electronic GmbH, Cologne,
Germany). Results: The skin was particularly distensible at the medial side of
the upper arm, followed by the earlobe, lower jaw, upper abdomen, lateral
abdomen, lower abdomen, and superior eyelid. It was poorly distensible at the
planta, followed by the anterior lower leg, palm, and forehead. The skin was
poorly elastic at the earlobe, superior eyelid, planta, and palm and highly
elastic at the lateral and upper abdomen, scapular region, and deltoid.
Conclusions: Except for the earlobe, all regions with poorly distensible and hard
skin are not prone to pathological scarring. This association between these skin
properties and abnormal scarring could be useful for skin surgeons.
PMID- 29942421
TI - Eyebrow and Eyelash Hair Transplantation: A Systematic Review.
AB - The objective of this systematic review was to investigate the etiologies of hair
loss of the eyebrow and eyelash that required hair transplantation, the optimal
surgical technique, patient outcomes, and common complications. A total of 67
articles including 354 patients from 18 countries were included in this study.
Most patients were women with an average age of 29 years. The most common
etiology requiring hair transplantation was burns, occurring in 57.6 percent of
cases. Both eyebrow and eyelash transplantation use follicular unit
transplantation techniques most commonly; however, other techniques involving
composite grafts and skin flaps continue to be utilized effectively with minimal
complication rates. In summary, many techniques have been developed for use in
eyebrow/eyelash transplantation and the selection of technique depends upon the
dermatologic surgeon's preferences and the unique presentations of their
patients.
PMID- 29942422
TI - A Case-control Study to Evaluate the Prevalence of Nonalcoholic Fatty Liver
Disease Among Patients with Moderate-to-severe Psoriasis.
AB - Objective: International case-control studies have demonstrated that psoriasis is
associated with an increased prevalence of nonalcoholic fatty liver disease
(NAFLD). The purpose of the present study was to establish an association of
psoriasis and NAFLD in patients attending a dermatology clinic center in the
United States. Design: This was an observational, case-control study. Setting:
The study setting was an outpatient dermatology clinic of the George Washington
Medical Faculty Associates in Washington DC. Participants: One hundred fifty-one
adult patients with psoriasis and 51 control subjects were recruited.
Measurements: NAFLD was diagnosed by ultrasonography after excluding secondary
causes of liver disease. Regression analysis was used to assess the associations
between: 1) NAFLD and psoriasis and 2) metabolic syndrome components and NAFLD
among psoriasis patients. Results: NAFLD was more prevalent in patients with
psoriasis (21.2% vs. 7.8%, p<0.04). However, psoriasis was not associated with
NAFLD when matching for age, sex, and body mass index (BMI) (odds ratio: 2.63,
95% confidence interval [CI]: 0.51-13.6; p=0.25). As compared to patients with
psoriasis but without NAFLD, those with NAFLD were more likely to have obesity
(BMI: 34.9 vs. 27.2, 95% CI: 32.4-37.5 vs. 25.9-28.5; p<0.01). NAFLD in patients
with psoriasis was also associated with select components of metabolic syndrome,
including hyperglycemia and hyperlipidemia. Conclusion: Our findings show there
is an association of psoriasis with NAFLD. Our findings also suggest an increased
presence of metabolic syndrome components in patients with psoriasis and NAFLD.
Trial registry: NCT00930384.
PMID- 29942423
TI - Use of Hyaluronic Acid Fillers to Correct Scleral Show: A Review of Technique.
AB - Generally, the shape of women's eyes are distinctly different in intercatal
height from that in men. Ideally, in a woman, the lateral intercostal point is
positioned above the medial intercostal point, which gives the eyes a cat-like
appearance that culturally suggests youth and health. Because of aging and/or
physiological changes, this area can be altered with the inversion of the lateral
intercantal line lower than the medial intercantal line, producing a tired and/or
sad looking appearance. Hyaluronic acid is a quick and safe method of elevating
the lateral intercantal area of the eye. This article describes a technique for
using hyaluronic acid for the treatment of scleral show.
PMID- 29942424
TI - An Open-label, Single-center, Prospective Evaluation of a Novel Noninvasive
Ultrasound Body Sculpting Device.
AB - : Objective: The goal of this study was to evaluate the safety and the efficacy
of the SlimMETM (Lumenis AB, Lumenis, Israel) ultrasound device for noninvasive
body contouring. Design: This was an open-label, single-arm, exploratory study.
Participants: Twenty adult patients presenting with subcutaneous target region
adipose fat thickness greater than 2.5cm were included in this study.
Measurements: Responses to a single treatment session with the ultrasound device
were assessed. Change from baseline in abdominal circumference was evaluated at
one, two, and three months posttreatment. Before and after treatment, the
physician scored improvements, patients completed a self-improvement assessment
questionnaire, and photographs were evaluated by three blinded reviewers.
Immediate skin responses were recorded for up to 30 minutes posttreatment, and
adverse events were recorded throughout the study. Results: A statistically and
clinically significant reduction in abdominal circumference was observed at three
months posttreatment, with a mean of -2.19+/-1.95cm, -2.14+/-1.94cm, and -1.83+/
2.00cm reduction from baseline in the umbilicus, under the ribs, and anterior
superior iliac spine (ASIS) circumference measurements, respectively. Physician
based assessments classified 89.5 percent of subjects as "improved" within three
months of treatment, and 89.5 percent of patients indicated their conditions to
be either improved or much improved within this same time period. Immediate skin
reactions were all expected, short-term, and self-resolving. Conclusions: A
single treatment session using the ultrasound study device appears safe and
effective in achieving noninvasive body contouring. TRIAL REGISTRY: NCT02849847.
PMID- 29942425
TI - Efficacy and Tolerability of an Acne Treatment Regimen with Antiaging Benefits in
Adult Women: A Pilot Study.
AB - Objective: The objective of this study was to assess clinical safety and efficacy
of a novel acne treatment regimen in adult women. Methods: Participants in the
study included an ethnically diverse group of adult women (n=24) with mild-to
moderate acne who were treated twice daily with a topical regimen (cleanser, acne
cream, and rebalancing gel) for eight weeks. Following baseline assessments,
subjects returned to clinic at Weeks 2, 4, and 8 for clinical assessments and
self-assessment questionnaires. Results: Twenty-one of the 24 enrolled women
completed the eight-week clinical trial. Statistically significant clinical
improvements were seen in both acne and aging parameters over time. The product
regimen was well tolerated without adverse reactions commonly seen with topical
acne products. Conclusion: The regimen demonstrated efficacy and tolerability in
adult women with acne and signs of skin aging.
PMID- 29942426
TI - This month's guideline: The Use of Hyaluronidase in Aesthetic Practice (v2.4).
PMID- 29942427
TI - Effect of Age, Gender and Hearing Loss on the Degree of Discomfort Due to
Tinnitus.
AB - Introduction: Tinnitus is one of the complex symptoms of hearing described as a
phantom auditory sensation without any external stimulation. Due to the
subjective nature of tinnitus, perception and discomfort of tinnitus vary among
the patients. The main aim of this study is to investigate the effects of gender,
age and the degree of hearing loss on discomfort due to tinnitus. Methods:
Eighteen patients with tinnitus, aged 21-72 years, (9 males and 9 females) were
recruited. Tinnitus discomfort was investigated by Tinnitus Handicap Inventory
(THI) questionnaire. Psychoacoustic assessments of tinnitus and auditory
threshold assessments were evaluated using a 2-channel clinical audiometer.
Results: The results showed no significant correlation between THI scores with
loudness matching (P=0.187), mean of auditory threshold (P=0.304), gender
(P=0.93) and age (P=0.200). Also, no significant correlation was found between
maximal level of hearing loss and pitch matching (P=0.208). Conclusion: The study
findings suggests that tinnitus is not correlated with age, gender and hearing
loss. Overall, tinnitus is a complicated clinical condition which its real impact
and degree of discomfort are unclear. More investigation is needed to clarify the
factors involving in tinnitus annoyance.
PMID- 29942428
TI - Protective Effects of Enriched Environment Against Transient Cerebral Ischemia
Induced Impairment of Passive Avoidance Memory and Long-Term Potentiation in
Rats.
AB - Introduction: Enriched Environment (EE), a complex novel environment, has been
demonstrated to improve synaptic plasticity in both injured and intact animals.
The present study investigated the capacity of an early environmental
intervention to normalize the impairment of passive avoidance memory and Long
Term Potentiation (LTP) induced by transient bilateral common carotid artery
occlusion (2-vessel occlusion, 2VO) in rats. Methods: After weaning, young Wistar
rats (22 days old) were housed in EE or Standard Environment (SE) for 40 days.
Transient (30-min) incomplete forebrain ischemia was induced 4 days before the
passive avoidance memory test and LTP induction. Results: The transient forebrain
ischemia led to impairment of passive avoidance memory and LTP induction in the
Perforant Path-Dentate Gyrus (PP-DG) synapses. Interestingly, housing and growing
in EE prior to 2VO was found to significantly reverse 2VO-induced cognitive and
LTP impairments. Conclusion: Our results suggest that early housing and growing
in EE exhibits therapeutic potential to normalize cognitive and LTP abnormalities
induced by 2VO ischemic model in rats.
PMID- 29942429
TI - Protective Role of Hypothermia Against Heat Stress in Differentiated and
Undifferentiated Human Neural Precursor Cells: A Differential Approach for the
Treatment of Traumatic Brain Injury.
AB - Introduction: The present study aimed to explore protective mechanisms of
hypothermia against mild cold and heat stress on highly proliferative homogeneous
human Neural Precursor Cells (NPCs) derived from Subventricular Zone (SVZ) of
human fetal brain. Methods: CD133+ve enriched undifferentiated and differentiated
human NPCs were exposed to heat stress at 42 degrees C. Then, Western-blot
quantification was performed using Hsp-70 (70 kilodalton heat shock proteins)
recombinant protein. Finally, changes in pluripotency and Hsp-70 expression were
measured using immunofluorescence staining and RT-qPCR (Quantitative reverse
transcription PCR) analysis, respectively. Results: Heat stress resulted in
abnormal neurospheres development. The apoptosis rate was enhanced during long
term in vitro culture of neurospheres. Neurogenic differentiation reduced and
showed aberrent phenotypes during heat stress. After hypothermia treatment
significant improvement in neurospheres and neuronal cell morphology was
observed. Conclusion: Mild-hypothermia treatment induces attenuated heat shock
response against heat stress resulting in induced HSP-70 expression that
significantly improves structure and function of both undifferentiated human NPCs
and differentiated neurons.
PMID- 29942430
TI - Chronic Pain and Selective Attention to Pain Arousing Daily Activity Pictures:
Evidence From an Eye Tracking Study.
AB - Introduction: According to the pain research literature, attentional bias for
pain is the mechanism responsible for the development and maintenance of fear of
pain in patients with chronic pain. However, there is still some debate about the
exact mechanism and the role of faster engagement versus difficulty in
disengagement in the development of attentional bias. Methods: To investigate
attentional bias in patients with chronic pain, we used an eye-tracker with the
pictures of pain-provoking activities and compared the results with an age- and
gender-matched group of pain-free participants. In addition, other measures of
pain-related cognition and pain severity ratings were included to assess their
contribution to the attentional bias toward pain-related information. Results:
Calculating the frequency of the first fixations showed that both groups fixated
initially on pain-provoking pictures compared to neutral one. Calculating the
speed of fixations showed that control participants were faster in fixating on
neutral stimuli, but patients with pain were faster in fixating on pain-provoking
pictures, indicating a relative vigilance for the pain-related stimuli among
them. These patients reported that the intensity of pain in the previous week was
positively correlated with the speed of their fixation on the painful stimuli.
Conclusion: Although these results did not provide unequivocal support for the
vigilance-avoidance hypothesis, they are generally consistent with the results of
studies using eye tracking technology. Furthermore, our findings put a question
over characterization of attentional biases in patients with chronic pain by
simply relating that to difficulty in disengaging from pain-related stimuli.
PMID- 29942431
TI - A Hybrid Approach Based on Higher Order Spectra for Clinical Recognition of
Seizure and Epilepsy Using Brain Activity.
AB - Introduction: This paper proposes a reliable and efficient technique to recognize
different epilepsy states, including healthy, interictal, and ictal states, using
Electroencephalogram (EEG) signals. Methods: The proposed approach consists of
pre-processing, feature extraction by higher order spectra, feature
normalization, feature selection by genetic algorithm and ranking method, and
classification by support vector machine with Gaussian and polynomial radial
basis function kernels. The proposed approach is validated on a public benchmark
dataset to compare it with previous studies. Results: The results indicate that
the combined use of above elements can effectively decipher the cognitive process
of epilepsy and seizure recognition. There are several bispectrum and bicoherence
peaks at every bi-frequency plane, which reveal the location of the quadratic
phase coupling. The proposed approach can reach, in almost all of the
experiments, up to 100% performance in terms of sensitivity, specificity, and
accuracy. Conclusion: Comparing between the obtained results and previous
approaches approves the effectiveness of the proposed approach for seizure and
epilepsy recognition.
PMID- 29942432
TI - Effect of WIN55-212-2 and Consequences of Extinction Training on Conditioned Fear
Memory in PTSD Male Rats.
AB - Introduction: This study investigates the effects of cannabinoid agonist WIN55
212-2 on acquisition and consolidation phases of the fear memory extinction and
also on anxiety and motor activity. Methods: In this study, we used SPS & S model
to induce post-traumatic stress disorder. One week after SPS, to establish a
conditioned fear memory, rats received an electric foot shock within shock
chamber. After 24 h, for extinction training, the rats were placed back to the
chamber for 9 min, without receiving any shock. In 3 consecutive days and on days
17, 24 and 37, extinction tests were carried out and the freezing behavior was
evaluated. Thirty minutes before the first three extinction tests, animals
received IP injections of WIN or vehicle. Anxiety-like behavior examined with
elevated plus-maze and motor activity with open field, 32 days after
conditioning. Results: Exaggerated and continued conditioned fear memory observed
in SPS & S group compared with shock group. IP injection of a 0.25 mg/kg dose of
WIN before extinction training led to reducing fear responses in animals.
Conclusion: IP injection of WIN increased acquisition or consolidation of fear
memory extinction. SPS & S caused anxiety and this effect improved by the agonist
(0.25 mg/kg).
PMID- 29942433
TI - In Vivo Psychopharmacological Investigation of Delphinium Denudatum and
Amaranthus Spinosus Extracts on Wistar Rats.
AB - Introduction: In our modern era, life style of human being changes and updates
every day that may affect their health status. There is an incredible expectation
that natural origin drugs lack undesirable effects not like synthetic drugs,
though have the same potency and efficacy. No scientific data is available about
the antianxiety properties of Delphinium denudatum root and Amaranthus spinosus
leaves. In this regard, the present study was designed to carry out comparative
and combined study on antianxiety properties of Delphinium denudatum root and
Amaranthus spinosus leaves. Methods: Delphinium denudatum root and Amaranthus
spinosus leaves were defatted with petroleum ether, and then extracted with
hydroalcoholic solvent by soxhlation process. The hydroalcoholic extract of both
drugs singly and in combination were evaluated for their anxiolytic effects on
Wistar albino rats in doses of 200 and 400 mg/kg using different anti-anxiety
tests like Elevated Plus Maze, Staircase, Actophotometer, and Light and Dark
tests. Results: Both hydroalcoholic extracts possessed flavonoids, alkaloids,
saponins, tannins, carbohydrates, proteins, amino acids, carbohydrates, steroids,
sterols, etc. In the dose dependent manner, both the hydroalcoholic extracts
produced good anxiolytic activity. The best result was obtained by a combination
of them in higher dose. Conclusion: Hydroalcoholic extracts of Delphinium
denudatum root and Amaranthus spinosus leaves and their combination may act as a
potent anxiolytic agents in rats. Amaranthus spinosus was found to be more
effective than Delphinium denudatum.
PMID- 29942434
TI - Commentary on "Co-Occurrence of Pituitary Adenoma With Suprasellar and Olfactory
Groove Meningiomas".
AB - Recently, Basic and Clinical Neuroscience published an article by Lim et al.
(2016) entitled Co-occurence of Pituitary Adenoma with Suprasellar and Olfactory
Groove Meningiomas. They claimed it as the first case of co-occurence of these
two malignancies. However, to our knowledge, this is not the first case reported
in this regard. We reported the same case scenario in a 61-year-old woman
referred to our outpatient clinic in 2007. In this commentary, we are going to
discuss our reported case and present a brief review over co-occurence of
intracranial meningioma with pituitary adenoma.
PMID- 29942435
TI - Comparison of Memory Impairment and Oxidative Stress Following Single or Repeated
Doses Administration of Scopolamine in Rat Hippocampus.
AB - Introduction: Scopolamine, a muscarinic cholinergic receptor antagonist, is
widely used to induce memory impairment in experimental animals. The present
study aims to compare memory impairment and oxidative stress following single and
repeated doses administration of scopolamine. Methods: A group of rats received a
single shot of scopolamine in different doses (0.5, 1, or 3 mg/kg, IP) 24 hours
after the passive avoidance training. Then the memory retrieval test was
performed 30 minutes and 7 days after the injection. In the other experiment,
rats received similar doses of scopolamine for 7 consecutive days, 24 hours after
the training session. Then the memory retrieval test was performed 30 minutes and
7 days after the last injection. Acetylcholinesterase (AChE) activity and lipid
peroxidation were measured in their hippocampus tissue, too. Results: Scopolamine
administered in repeated doses caused more impairment in memory function compared
to single dose injection based on the evaluation 30 minutes after injection.
Moreover, the memory impairment persisted for 7 days only in repeated doses
treated groups. Increase in acetylcholinesterase activity and lipid peroxidation
in both groups was observed 30 minutes after scopolamine administration. These
abnormal increases persisted for 7 days only in repeated doses treated groups.
Increased AChE activity and lipid peroxidation was well correlated with
behavioral deficit. Also AChE activity was well associated with lipid
peroxidation. Conclusion: The results of present study showed that repeated
administration of scopolamine induced results in memory impairment. This effect
can be due to long-lasting oxidative stress which may damage the hippocampus
tissue.
PMID- 29942436
TI - Generating the Visual Biofeedback Signals Applicable to Reduction of Wrist
Spasticity: A Pilot Study on Stroke Patients.
AB - Introduction: Application of biofeedback techniques in rehabilitation has turned
into an exciting research area during the recent decade. Providing an appropriate
visual or auditory biofeedback signal is the most critical requirement of a
biofeedback technique. In this regard, changes in Surface Electromyography (SEMG)
signals during wrist movement can be used to generate an indictable visual
biofeedback signal for wrist movement rehabilitation via SEMG biofeedback. This
paper proposes a novel methodology for selecting the most appropriate features
out of wrist muscle SEMG signals. Methods: To this end, the surface EMG signals
from flexor and extensor muscle groups during wrist joint movements were recorded
and analyzed. Some linear and nonlinear features in frequency, time, and time
frequency domains were extracted from the recorded surface EMG signals of the
flexor and extensor muscles. Experiments and analyses were performed on ten
healthy subjects and four stroke patients with wrist muscle spasticity as the
movement disorder subjects. Some heuristic feature selection measures were
applied. The main motivation behind choosing applied heuristic feature selection
measures was meeting. In the first step, the designed visual biofeedback signal
should indicate a healthy wrist motion profile as its successful tracking by the
patient guarantees rehabilitation. In addition, the visual biofeedback signal
should be a smooth curve thus preventing the patient from discomfort while
tracking it on a monitor during the biofeedback therapy. Results: In this pilot
study, after using the introduced feature selection measures, quantitative and
qualitative analyses of the extracted features indicated that Shannon entropy is
the most appropriate feature for generating a visual biofeedback signal as a
healthy wrist motion profile to improve the ability of stroke patients in
controlling wrist joint motion. In addition, it was shown that when the wrist
joint moves between a flexed and rest position, the flexor muscle EMG signal
should be used for generating a visual biofeedback signal. However when the wrist
joint moves between a rest position and an extended position, the extensor muscle
EMG signal is appropriate for providing a visual biofeedback signal. It is worth
noting that the achieved pilot study results should be confirmed by the future
studies with larger samples. Conclusion: According to the obtained results, it
can be concluded that among the analyzed features, the Shannon entropy was the
most appropriate feature. It can be employed for generating a visual biofeedback
signal for reduction of spasticity in patients with stroke.
PMID- 29942437
TI - Stereological Method for Assessing the Effect of Vitamin C Administration on the
Reduction of Acrylamide-induced Neurotoxicity.
AB - Introduction: Acrylamide (ACR) consumption is increasing all over the world.
There are some evidence on the literature about its neurotoxic effect on mature
animals, but the effects of ACR on postnatal development have been less studied.
The purpose of this study was to evaluate the effects of ACR on development of
cortical layer, white matter, and number of Purkinje cells of the cerebellum in
rat newborns. Methods: This study was carried out on 20 female Wistar rats
(average weight: 180 g, aged: two months). The rats were divided into four
groups. Pregnant rats were orally fed with ACR 10 mg/kg and vitamin C 200 mg/kg.
In this study, 6 infants of each group (weighting 32-35 g) were randomly selected
at day 21 after birth and placed under deep anesthesia and transcardial
perfusion. Their cerebellums were fixed and histopathological changes were
evaluated with Hematoxylin and Eosin (H&E) staining and cresyl violet method. The
volume of cerebellar cortical layers and number of Purkinje cells were
investigated by Cavalieri's principle and physical dissector methods. The
obtained data were analyzed by 1-way ANOVA and LSD test using SPSS. P<0.05
considered as statistically significant. Results: The results showed that
newborns of ACR-treated female rats have decreased cerebellar weight (P<=0.05)
and lower than average number of Purkinje cells (P<=0.001). ACR also decreased
the volume of granular and molecular layer and increased the volume of white
matter. While the results showed decreased in white matter volume in vitamin C
group (P<=0.001). Conclusion: ACR induces structural changes in the development
of the cerebellar cortical layers in rat newborns, but these changes may be
prevented by vitamin C as an antioxidant.
PMID- 29942438
TI - Development, Cross-Cultural Adaptation, and Psychometric Characteristics of the
Persian Progressive Aphasia Language Scale in Patients With Primary Progressive
Aphasia: A Pilot Study.
AB - Introduction: Primary Progressive Aphasia (PPA) is a neurological condition
characterized by progressive dissolution of language capabilities. The
Progressive Aphasia Language Scale (PALS) is an easy-to-apply bedside clinical
scale capable of capturing and grading the key language features essential for
the classification of PPA. The objective of the present study was to develop and
validate the Persian version of the PALS (PALS-P) as a clinical language
assessment test. Methods: In this cross-sectional study, PALS was translated and
adapted into Persian according to the international guidelines. A total of 30
subjects (10 subjects with PPA and 20 control subjects without dementia) were
recruited to evaluate the intra-rater reliability and discriminant validity of
PALS-P. Results: The intra-rater reliability of the PALS-P within a 14-day
interval was excellent for each subtest (ICC agreement range=0.81-1.0). PALS-P
results were statistically significant among groups, suggesting its
discriminative validity. Conclusion: This preliminary study indicates that PALS-P
was successfully developed and translated. It seems to be a valid and reliable
screening tool to assess language skills in Persian-speaking subjects with
progressive aphasia.
PMID- 29942439
TI - Discordant Relationship Between Evaluation of Facial Expression and Subjective
Pain Rating Due to the Low Pain Magnitude.
AB - Introduction: Facial expression to pain is an important pain indicator; however,
facial movements look unresponsive when perceiving mild pain. The present study
investigates whether pain magnitude modulates the relationship between subjective
pain rating and an observer's evaluation of facial expression. Methods: Twelve
healthy volunteers were recruited to obtain 108 samples for pain rating with
Visual Analogue Scale (VAS). Subjects underwent three different mechanical
painful stimuli (monofilament forces of 100 g, 300 g, and 600 g) over three
sessions and their facial expressions were videotaped throughout all sessions.
Three observers independently evaluated facial expression of the subjects with a
four-point categorical scale (no pain, mild pain, moderate pain, and severe
pain). The correlations between subjective pain ratings and the evaluation of
facial expression were analyzed in dichotomous group which was low pain ratings
(VAS<30), or high pain rating (VAS>=30). Results: Subjective pain ratings was
significantly correlated with the evaluation of facial expression in high pain
ratings, however no correlation was found between them in mild pain ratings. In
mild pain ratings, most of the subjects (78%) were rated as no pain by observers,
despite the fact that subjects reported pain. Conclusion: The results suggest
that the evaluation of facial expression of pain was difficult for the observer
to detect pain severity when the subjects feel mild pain.
PMID- 29942440
TI - Low Frequency Stimulation Reverses the Kindling-Induced Impairment of Learning
and Memory in the Rat Passive-avoidance Test.
AB - Introduction: The life quality of patients with epileptic seizures is highly
affected by cognitive deficits. Low Frequency Stimulation (LFS) is a novel
approach for the treatment of pharmacoresistant epilepsy. The main goal of this
research is investigating the possible effect of LFS on seizure-induced cognitive
dysfunction. Methods: To this end, the kindled animal were prepared via CA1
electrical stimulation in a semi-rapid way (12 stimulations/day). A group of
animals were stimulated with LFS, 4 times at 30 s, 6 h, 24 h, and 30 h after the
last kindling stimulation. Applied LFS was administered in 4 packages every 5
minutes. The packages were designed with 200 monophasic 200 monophasic square
wave pulses of 0.1 ms duration at 1 Hz. The passive-avoidance test was conducted
on all animals in order to measure the learning and memory behavior. Results:
Hippocampal kindled rats showed deficits in learning and memory when passive
avoidance test was performed. Application of LFS reversed the impairment in
learning and memory behavior in kindled rats. At the same time, LFS markedly
diminished kindling-induced neuronal loss and atrophy in the hippocampus.
Conclusion: LFS may have some protection against seizure-induced cognitive damage
in kindled rats.
PMID- 29942441
TI - The Relationship Between Salivary Alpha Amylase Activity and Score of McGill Pain
Questionnaire in Patients With Tension Type Headache.
AB - Introduction: Tension-type headache is the most common type of headache across
the world. Saliva as a non-invasive medium is used to detect a wide range of
diseases. Salivary Alpha-Amylase (SAA) levels has been suggested as a potential
indirect marker for detecting Sympathoadrenal Medullary (SAM) activity, which is
activated by pain. Significant correlation was found between SAA levels and pain
scale in patients with chronic pain. The purpose of the present study was to
measure SAA activity in Frequent Episodic Tension-Type Headache (FETTH). In
addition to the Visual Analogue Scale (VAS), we intend to assess intensity and
various aspects of pain by McGill Pain Questionnaire (MPQ). Methods: A total of
45 females with FETTH (case group) and 45 healthy voluntary females (control
group) were enrolled in our case-control study. Unstimulated saliva by spitting
method was taken from each participant. Results: SAA levels were significantly
higher in patients with FETTH (P<0.001) when compared with the control group.
There was significant correlation between SAA activity and MPQ score (P<0.001).
Conclusion: This is the first study using MPQ as a subjective means of assessing
quality and quantity of pain alongside the VAS as an objective tool for
evaluating pain in patients with FETTH. SAA may be an appropriate marker for
assessing of pain levels in patients with FETTH. MPQ versus the VAS may be a more
accurate measurement tools along VAS.
PMID- 29942442
TI - Comparison Between Three-Dimensional Diffusion-Weighted PSIF Technique and
Routine Imaging Sequences in Evaluation of Peripheral Nerves in Healthy People.
AB - Introduction: The present study aims to evaluate the Three-Dimensional Diffusion
Weighted reversed fast imaging with steady state free precession (3D DW-PSIF)
sequence with respect to imaging of the peripheral nerves; the tibial, medial,
and lateral plantar nerves in the lower extremity, ulnar and median nerve in the
upper extremity, sciatic nerve, brachial plexus, and lumbosacral plexus, and also
to compare its usefulness with the current two-dimensional sequences on a 1.5 T
MR scanner. Methods: A total of 25 healthy subjects underwent MR imaging of
peripheral nerves, 5 subjects in each area. In each imaging sequence, including
T2W SPAIR and 3D DW-PSIF, images were evaluated for ability to identify the
nerves in the related area using a 3-score scale (0-2). Then, by summing up the
conspicuity scores, a total certainty score was recorded for each sequence.
Results: With combining the results of all studies, the conspicuity mean (SD)
score was 1.57(0.67) on the 3D DW-PSIF images, and 0.74(0.76) on the T2-weighted
images (P<0.001). Regarding the lumbosacral plexus, the corresponding certainty
mean (SD) scores were 1.80(0.40) and 1.07(0.74) (P<0.001) and with regard to the
brachial plexus, they were 1.23(0.83) and 0.75(0.84), (P<0.001). Regarding the
ankle/hind foot they were 1.87(0.35) and 0.40(0.50) (P<0.001) and in the
wrist/proximal hand, 1.70(0.48) and 0.50(0.52) (P<0.001). Regarding the sciatic
nerve, they were 1.80(0.44) and 0.20(0.44) (P=0.003). Conclusion: 3D DW PSIF
provides better manifestation of nerves compared to routine imaging sequences
particularly fat saturated T2W images. This novel imaging technique can be used
in MR neurography examination protocol for exact localization of the nerve and
evaluation of the nerve pathology.
PMID- 29942443
TI - The fate of neurons after traumatic spinal cord injury in rats: A systematic
review.
AB - Objectives: To reach an evidence-based knowledge in the context of the temporal
spatial pattern of neuronal death and find appropriate time of intervention in
order to preserve spared neurons and promote regeneration after traumatic spinal
cord injury (TSCI). Materials and Methods: The study design was based on
Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)
guided systematic review. PubMed and EMBASE were searched (24 October, 2015) with
no temporal or linguistic restrictions. Hand-search was performed in the
bibliographies of relevant articles. Non-interventional animal studies evaluating
time-dependent neuronal death following acute mechanical trauma to the spinal
cord were included. We separately evaluated the fate of various populations of
neurons including propriospinal neurons, ventral motor neurons, Clarke's column
neurons, and supraspinal neurons. Results: We found 11,557 non-duplicated
studies. Screening through the titles and abstracts led to 549 articles, 49 of
which met the inclusion criteria. Both necrotic and apoptotic neuronal deaths
occur after TSCI, though necrosis is the prominent mechanism. There are
differences in the responses of intrinsic neurons of the spinal cord to the TSCI.
Also, the extent of neuronal death in the supraspinal neurons depends on the
anatomical location of their axons. Conclusion: In order to develop new
therapies, selection of the injury model and time of intervention has a crucial
role in the efficacy of therapy. In addition, examining the safety and efficacy
of an intervention by reliable methods not confounded by the injury-related
changes would promote translation of therapies to the clinical application.
PMID- 29942444
TI - Mild exercise along with limb blood-flow restriction modulates the
electrocardiogram, angiotensin, and apelin receptors of the heart in aging rats.
AB - Objectives: Considering the lack of information, the effects of mild endurance
exercise plus blood flow restriction (BFR) on electrocardiographic parameters,
hypertrophy index, and expression of angiotensin II receptors type 1 (AT1R) and
type 2 (AT2R) and apelin receptor (APJ) were assessed in hearts of old male rats.
Materials and Methods: Animal were grouped as control (CTL), Sham (Sh), lower
extremities blood flow restriction (BFR), exercise (Ex), Sham + exercise (Sh +
Ex), and blood flow restriction + exercise (BFR + Ex). Results: Exercise plus BFR
significantly decreased the corrected QT (QTc) interval (P<0.01 vs CTL and Sh
groups) and increased the heart hypertrophy index (P<0.05 vs CTL and BFR groups).
Exercise alone increased expression of the APJ (P<0.01, vs CTL, Sh, and BFR
groups) and AT2 receptors (P<0.001, vs Sh, CTL, BFR, and BFR + exercise groups),
whereas it reduced expression of AT1R (P<0.01 in comparison with CTL, Sh, and BFR
groups). Exercise plus BFR caused a significant increase in APJ (P<0.05 vs Ex,
Sh+Ex and P<0.001 vs CTL, Sh, and BFR groups) and also expression of AT1R
(P<0.001 vs Ex, Sh + Ex, CTL, Sh, and P<0.01 vs BFR groups). Accompaniment of
exercise with BFR destroyed the effect of exercise on the expression of AT2R.
Conclusion: Mild endurance exercise plus BFR can alter the expression of
angiotensin II and apelin receptors that leads to cardiac hypertrophy and
improves the ventricular conductivity of aging rats.
PMID- 29942445
TI - Protective role of HLA-DRB1*11 against juvenile idiopathic arthritis living in
North Eastern Iran.
AB - Objectives: Juvenile idiopathic arthritis (JIA) is one of the most common chronic
rheumatic diseases in children. The complex nature of this immune-mediated
disease owes itself to several predisposing genes and environmental factors
affecting its pathogenesis. Conducted in Iran, this study was originally intended
to investigate every possible association between HLA DRB1 alleles and a
susceptibility to JIA. Materials and Methods: In this case-control study, 45
patients with a definite diagnosis of JIA based on International League against
Rheumatism (ILAR) criteria were compared against 46 healthy controls. DNA samples
taken from both groups were analyzed using PCR-sequence specific primers (PCR
SSP) method. Data analysis including parametric and nonparametric test and
multivariate analysis was undertaken using the SPSS 11.5 software. A P-value<
0.05 was regarded as statistically significant. Results: Mean ages in case group
and healthy controls were 14.64+/-6.21 and 13.73+/-6.39, respectively with no
significant difference between the two groups (P=0.515). Sex difference between
JIA group and healthy controls was also not significant (P=0.068). The frequency
of HLA-DRB1*01 was found the most frequent HLA-RB1 in our patients (33.3%). No
significant statistical correlation between various HLA-DRB1 alleles and clinical
subtypes of the disease could be established from the data. HLA-DRB1*11 was shown
to raise protection to JIA (P=0.035, OR=2.755, 95% CI=0.963-8.055) in
northeastern Iran. In addition, we found that HLA-RB1*09 is nominally associated
with an increased risk of JIA (P=0.56, OR=2, 05, 95% CI=0.18-23.63). Conclusion:
HLA-DRB1*11 was shown to raise protection to JIA in northeastern Iran. The
disparity of findings in other ethnicities prompts further investigations with
larger sample sizes.
PMID- 29942446
TI - Effect of combination therapy with pramipexole and n-acetylcysteine on global
cerebral ischemic reperfusion injury in rats.
AB - Objectives: The study was intended to investigate the combined influence of two
neuroprotective agents pramipexole and n-acetylcysteine on global cerebral
ischemic reperfusion injury (GCIRI) model in rats. Materials and Methods: GCIRI
was induced by bilateral common carotid artery ligation (BCCA) in rats. Animals
were divided into six groups. Groups I, II, and III received saline
intraperitoneally (IP) (5 ml/kg/day, 0.9 % saline). The remaining groups IV, V,
and VI were treated with n-acetylcysteine (NAC-150 mg/kg/day, IP), pramipexole
(PPX-0.23 mg/kg/day, IP) alone and in combination, respectively. BCCA was done in
all groups except in groups I (control) and II (sham control) of animals. The
treatment was given for one week before the surgery and continued for two days
after surgery. Subsequently, behavioral performances, biochemical estimations,
proinflammatory cytokines, and histopathological evaluations were done. Results:
NAC, PPX, and combination treatment groups showed significant ameliorative
effects on behavioral, biochemical, proinflammatory cytokines, and
histopathological studies as compared with the BCCA group. Whereas, the
combination group showed a significant difference in ameliorating the
pathological changes of biochemical parameters and histopathological changes in
comparison with the PPX alone treated group but not with the NAC alone group.
Conclusion: The study concluded that in the combination treatment group the
histopathological parameter improved and the oxidative stress parameters were
mitigated significantly compared with the PPX alone treatment group but not with
the NAC alone treatment group.
PMID- 29942447
TI - Selenium supplementation in the form of selenium nanoparticles and selenite
sodium improves mature male mice reproductive performances.
AB - Objectives: The current study was conducted to examine the possible protective
and retentive effects of one-week intra-peritoneal (IP) administration of
selenium nanoparticles (Se-NPs), compared to its bulk counterpart, selenite
sodium (Ss), after one complete cycle of spermatogenesis in mature male mice.
Materials and Methods: Thirty adult male mice were divided into 3 groups. Control
group was administrated phosphate-buffered saline (IP) and the other groups
received Ss (0.50 mg kg-1) and Se-NPs (0.50 mg kg-1) for seven successive days.
Then, the animals were monitored for 28 days and finally sacrificed and tissue
and blood samples were taken. Histopathological features, sperm quality, in vitro
fertilization (IVF) capability and selenium (Se) content in testicular tissue
were analyzed. Antioxidant enzyme activities including catalase, glutathione
peroxidase, and superoxide dismutase as well as total antioxidant capacity and
malondialdehyde levels were assessed in blood and the tissue samples. Results:
Remarkable differences were found in sperm characteristics, histopathological
features and oxidative stress biomarkers between control and treatment groups.
Moreover, IVF evaluation and tissue Se concentration examination weren't similar
for Se-NPs and Ss. Conclusion: Conclusively, Se-treated groups had more
antioxidant capacity than the control group, but sperm quality and
histopathological features revealed that Se-NPs might possess more antioxidative
and retentive potential compared to Ss in one spermatogenesis cycle.
PMID- 29942448
TI - Cholesteryl ester transfer protein gene variations and macronutrient intakes
interaction in relation to metabolic syndrome: Tehran lipid and glucose study.
AB - Objectives: There are controversial results regarding the effect of the
interaction of CETP polymorphisms with dietary fats on the lipid profiles. The
aim of this study was to examine the effect of CETP polymorphisms (rs5882 and
rs3764261) and macronutrient intakes interaction in relation to metabolic
syndrome (MetS) or its components. Materials and Methods: In this nested case
control study, subjects were selected from among participants of the Tehran Lipid
and Glucose Study. Cases (n=441) were individually matched with two controls (844
non-MetS subjects). DNA samples were genotyped with HumanOmniExpress-24-v1-0 bead
chips, including 649,932 SNP loci. Results: The mean ages at baseline were 38.1+/
10 and 37.0+/-10 years in women and 36.2+/-11 and 36.3+/-11 years in men,
respectively in cases and controls. We did not find significant gene-diet
interactions between rs5882 and dietary macronutrient intakes in relation to MetS
risk. The risk of low HDL-C was lower in the first quartile of MUFA and total fat
intake in G allele carriers, compared to AA genotype group. The risk of high BP
appeared to increase significantly in higher quartiles of trans-fatty acid
intakes (>1.81% of total energy intake) in G allele carriers compared with the AA
genotype group. No significant interactions were found between rs3764261 and
macronutrient intakes in association with MetS or its components. Conclusion: Our
findings demonstrate that dietary fats modify the association of rs5882 and risk
of low HDL-C and high blood pressure.
PMID- 29942449
TI - Protective effects of vitamin D on ischemia-reperfusion injury of the ovary in a
rat model.
AB - Objectives: The aim of the present study is to investigate probable acute effects
of vitamin D on ischemia-reperfusion injury in the rat ovary. Materials and
Methods: A group of 30 Wistar albino rats was divided into five groups of 6 each.
Group 1: underwent laparotomy only and the ovaries were removed. Group 2: 3-hr
ischemia followed by excision of the ovaries. Group 3: 3-hr ischemia and 3-hr
reperfusion and the ovaries were removed. Group 4: vitamin D was administered 30
min prior to the 3-hr of ischemia and the ovaries were excised at the end of
ischemia period. Group 5: vitamin D was administered 30 min prior to the 3-hr of
ischemia and 3-hr reperfusion then the ovaries were removed at the end of
reperfusion. The ovaries excised in each group also underwent biochemical and
histopathologic analysis. MDA (malondialdehyde), SOD (superoxide dismutase), NO
(nitric oxide), TAS (total antioxidant score), TOS (total oxidant score) were
analyzed as biochemical parameters. Results: There were no significant
differences between groups in TAS, TOS, or OSI (P>0.05). MDA levels were lower in
the vitamin D treatment groups especially in group 5, significantly (P<0.05). In
the histopathologic evaluation, we established that an improvement with vitamin D
treatment. According to tissue injury scores, vascular congestion score was
significantly different between group 3 and 5 (P<0.05). Conclusion: Vitamin D
seems an effective molecule for protection of ischemia-reperfusion injury in rat
ovary. There is some significant improvement in oxidative damages with vitamin D
treatment.
PMID- 29942450
TI - The role of nitric oxide in the protective action of remote ischemic per
conditioning against ischemia/reperfusion-induced acute renal failure in rat.
AB - Objectives: We investigated the role of nitric oxide (NO) in the protective
effects of remote ischemic per-conditioning (rIPerC) on renal
ischemia/reperfusion (I/R) injury in male rats. Materials and Methods: I/R
treatment consisted of 45 min bilateral renal artery ischemia and 24 hr
reperfusion interval. rIPerC was performed using four cycles of 2 min occlusions
of the left femoral artery and 3 min reperfusion at the beginning of renal
ischemia. The animals were given normal saline (vehicle), NG-nitro-L-arginine
methyl ester (L-NAME) or L-arginine. Following the reperfusion period, renal
functional- and oxidative stress- parameters, as well as histopathological
changes were assessed. Results: In comparison with the sham group, I/R resulted
in renal dysfunction, as indicated by significantly lower creatinine clearance
and higher fractional excretion of sodium. This went along with decreased
glutathione peroxidase (GPX) and catalase (CAT) activity in the I/R group,
increased malondialdehyde (MDA) contents and histological damages. In comparison
with the I/R group, the rIPerC group displayed improved renal function, increased
activity of GPX and CAT enzymes, and decreased MDA level. However, these effects
were abrogated by L-NAME injection and augmented by L-arginine treatment.
Conclusion: According to the results, the functional and structural consequences
of rIPerC against I/R-induced kidney dysfunction, which is associated with
reduction of lipid peroxidation and intensification of anti-oxidant systems, is
partially dependent on NO production.
PMID- 29942451
TI - Zatariamultiflora ameliorates cisplatin-induced testicular damage via suppression
of oxidative stress and apoptosis in a mice model.
AB - Objectives: Cisplatin (CP), as an anti-neoplastic drug, causes testicular damage.
Zataria multiflora Boiss (ZM), a medicinal plant, has antioxidant and anti
inflammatory properties. The aim of this study was to investigate the effects of
ZM against CP-induced testicular toxicity. Materials and Methods: In this
experimental study, thirty-two adult male mice were randomly divided into four
groups. The control group received normal saline with oral gavage during 7 days;
ZM group received ZM (200 mg/kg) during 7 days by gavage; CP group received CP
(10 mg/kg) intraperitoneally (IP) in the 5th day of study; ZM + CP group received
ZM during 7 days and CP was injected in 5th day. Sperm parameters, biochemical
(MDA, GSH, and PC) levels, serum testosterone levels, and histopathological and
immunohistochemical assays of testis were examined one day after the last drug
treatment. Results: CP treatment caused significant damage via changed sperm
parameters (sperm motility, count, viability rate, and abnormalities), increased
oxidative stress (increased MDA and PC levels, and decreased GSH level),
histological changes (degeneration, necrosis, arrest of spermatogenesis,
congestion, and decrease in thickness of the germinal epithelium, diameter of
seminiferous tubules, and Johnsen's Score), decreased serum testosterone level,
and increased caspase-3 immunoreactivity. ZM preserved spermatogenesis and
mitigated the toxic effects of CP on the testis tissue. In addition, treatment
with ZM significantly reduced caspase-3 immunoreactivity. Conclusion: The
findings of this study suggest that ZM as a potential antioxidant compound and
due to free radicals scavenging activities has a protective effect against CP
induced testicular toxicity.
PMID- 29942452
TI - Does inhibition of angiotensin function cause neuroprotection in diffuse
traumatic brain injury?
AB - Objectives: Neuroprotection is created following the inhibition of angiotensin II
type 1 receptor (AT1R). Therefore, the purpose of this research was examining
AT1R blockage by candesartan in diffuse traumatic brain injury (TBI). Materials
and Methods: Male rats were assigned into sham, TBI, vehicle, and candesartan
groups. Candesartan (0.3 mg/kg) or vehicle was administered IP, 30 min post-TBI.
Brain water and Evans blue contents were determined, 24 and 5 hr after TBI,
respectively. Intracranial pressure (ICP) and neurologic outcome were evaluated
at -1, 1, 4 and 24 hr after TBI. Oxidant index [malondialdehyde (MDA)] was
determined 24 hr after TBI. Results: Brain water and Evans blue contents, and MDA
and ICP levels increased in TBI and vehicle groups in comparison with the sham
group. Candesartan attenuated the TBI-induced brain water and Evans blue
contents, and ICP and MDA enhancement. The neurologic score enhanced following
candesartan administration, 24 hr after TBI. Conclusion: The blockage of AT1R may
be neuroprotective by decreasing ICP associated with the reduction of lipid
peroxidation, brain edema, and blood-brain barrier (BBB) permeability, which led
to the improvement of neurologic outcome.
PMID- 29942453
TI - Radiosensitizing effects of Sestrin2 in PC3 prostate cancer cells.
AB - Objectives: The stress-responsive genes of Sestrin family are recognized as new
tumor suppressor genes in breast carcinoma, however, the function of Sestrin
family in human prostate cancer is not clear. Ionizing radiation (IR) is known to
induce Sestrin gene expression in breast cancer cells. However, the response of
Sestrin to IR has not been reported in PC3 prostate cancer cells. Materials and
Methods: Sestrin2 expression in prostate cancer cell lines (PC3, LNCaP clone FGC,
and DU145) was detected by Western blot and real-time PCR. Cell counting kit (CCK
8) was used to detect cellular proliferation. The radiosensitivity of PC3 cells
was detected by clonogenic assay. Results: Sestrin2 expression in prostate cancer
cell lines (PC3, LNCaP clone FGC, and DU145) is low. In vitro assays indicated
that over-expressing Sestrin2 in human prostate cancer PC3 inhibited tumor
proliferation. In addition, elevated Sestrin2 expression sensitized PC3 cells to
IR. Conclusion: We determined Sestrin2 may function as a tumor suppressor through
repressing proliferation, mediating sensitization to IR in PC3 cells.
PMID- 29942454
TI - Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and
peripheral antinociceptive effect of thymoquinone in rats.
AB - Objectives: Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel
pathway has a modulatory role in pain perception. Previous studies have shown
that thymoquinone exerts antinociceptive effects; however, the mechanisms
underlying antinociception induced by thymoquinone have not been fully clarified.
The aim of the present study was to evaluate the role of L-arginine/NO/cGMP/KATP
channel pathway in the central and peripheral antinociceptive effect of
thymoquinone in rats. Materials and Methods: Rats were pretreated intraplantarly
(IPL) or intracerebroventricularly (ICV) with L-arginine (the NO precursor), l
NAME (an NO synthase inhibitor), SNAP (an NO donor), methylene blue (a guanylyl
cyclase inhibitor), glibenclamide (the blocker of KATP channel), and
tetraethylammonium (TEA, a Kv channel blocker) before the injection of
thymoquinone. Results: Local ipsilateral (20 and 40 MUg, IPL) but not
contralateral and ICV (4 and 8 MUg) administration of thymoquinone caused a dose
dependent and significant antinociception in both early and late phases of the
formalin test. Pretreatment of rats with L-arginine (100 MUg, IPL or ICV) and
SNAP (200 MUg, IPL or ICV) increased while l-NAME (100 MUg, IPL or 1 MUg, ICV)
and methylene blue (400 MUg, IPL or ICV) decreased the antinociceptive effects of
thymoquinone in the formalin test. The administration of TEA (IPL or ICV) did not
modify but glibenclamide (50 MUg, IPL or ICV) significantly abolished the
peripheral and central antinociceptive effects of thymoquinone in both phases of
the formalin test. Conclusion: The results of the present study indicate that L
arginine/NO/cGMP/KATP channel pathway participates in the central and peripheral
antinociceptive effect of thymoquinone.
PMID- 29942455
TI - The role of autophagy in advanced glycation end product-induced proliferation and
migration in rat vascular smooth muscle cells.
AB - Objectives: To investigate the role of autophagy in advanced glycation end
products (AGEs)-induced proliferation and migration in rat vascular smooth muscle
cells (VSMCs). Materials and Methods: After culture, VSMCs were treated with 0,
1, 10, and 100 MUg/ml concentrations of AGEs. Autophagy specific protein light
chain 3 (LC3)-I/II was determined by western blotting, autophagosomes were
observed with electron microscopy, cell proliferation was quantified using the
methyl thiazolyl tetrazolium (MTT) assay, and cell migration was evaluated using
Transwell migration and scratch assays. Results: Compared to the control group,
the level of LC3- II/I in AGEs treatment group was up-regulated, and the number
of autophagosomes was also increased. Furthermore, in concentration of 100 MUg/ml
AGEs, the extent of proliferation and migration was significantly increased
compared to the control group. However, pretreating cells with autophagy
inhibitor 3-MA could attenuate these effects. Conclusion: Our study demonstrated
that AGEs-induced autophagy accelerated AGEs-stimulated proliferation and
migration in VSMCs.
PMID- 29942456
TI - Melatonin ameliorates testicular damages induced by nicotine in mice.
AB - Objectives: Nicotine as a toxic substance leads to impairment of the reproductive
system function. The aim of this study was to evaluate effects of melatonin on
testicular alterations, sperm nuclear integrity, and epididymal sperm parameters
in mice treated with nicotine. Materials and Methods: Male mice were divided into
four groups. Group A received the vehicle, group B received nicotine 0.1 mg/100 g
BW, group C received melatonin 10 mg/kg, group D received nicotine plus
melatonin. Evaluations were made by histology and Johnson's score for study of
spermatogenesis, immunostaining for study of male germ cells apoptosis, sperm
chromatin dispersion (SCD) test for assaying sperm chromatin integrity, enzyme
linked immunosorbent assay (ELISA) for assessment of serum levels of testosterone
and luteinizing hormone (LH), and sperm parameters including morphology,
motility, and count. Results: Nicotine caused a significant decrease in
spermatogenesis quantity and Johnson's score, sperm parameters, and sex hormones.
Melatonin in group D, increased sperm chromatin integrity, improved
spermatogenesis, Johnson's score, and sperm parameters (P<.01) and reduced
apoptosis (P <0.01) in comparison with the nicotine group. Melatonin
significantly increased testosterone and halo sperms. However, its effect on the
LH level was insignificant. The serum testosterone and LH levels were negatively
correlated with the DNA fragmentation index (DFI) (r= -0.86, P<0.001) and (r=
0.78, P<0.001), respectively. Conclusion: this study showed administration of
melatonin in nicotine-treated mice increases both quality and quantity of
spermatogenesis and integrity of sperm's chromatin through reducing apoptosis and
modifying the testosterone level.
PMID- 29942457
TI - Hydroalcoholic extract of flaxseed improves polycystic ovary syndrome in a rat
model.
AB - Objectives: Herbal medicines are an alternative choice for treatment or
controlling of polycystic ovary syndrome (PCOS). Effect of hydroalcoholic extract
of flaxseed was evaluated on ovarian hormones and histological changes of uterus
and ovary in a PCOS-induced rat model. Materials and Methods: Twenty four rats
divided into four groups including negative control, positive control, PCOS and
treatment groups. Positive control group received hydroalcoholic extract of
flaxseed for 30 days. PCOS was induced by single intramuscular injection of
estradiol valerate. Treatment group was treated with flaxseed extract 7 weeks
after induction of PCOS for 30 days. Ovaries and uterus were dissected out and
their sections were used for histomorphometric study. Levels of estradiol,
progesterone, testosterone and dehydroepiandrosterone (DHEA) were measured in the
serum. Results: In the treatment group, flaxseed extract increased level of
progesterone (P<0.05), while decreased testosterone (P<0.05) compared with the
PCOS group. Concentrations of estrogen and DHEA did not change significantly in
comparison with the PCOS group. Histomorphometric study showed that in the
treatment group, the number of preantral follicles, antral follicles and corpus
luteum increased compared with the PCOS group (P<0.05), but the number of cystic
follicles and diameter of antral follicles decreased (P<0.05), and the number of
primary follicle did not alter significantly. In the treatment group, the
thickness of granulosa layer increased, but the thickness of theca layer and
tunica albuginea decreased compared to the PCOS group (P<0.05). Conclusion:
Hormonal profile and histomorphometric features of ovary that were disturbed by
PCOS induction were ameliorated by hydroalcoholic extract of flaxseed.
PMID- 29942458
TI - Functional acclimation across microgeographic scales in Dodonaea viscosa.
AB - Intraspecific plant functional trait variation provides mechanistic insight into
persistence and can infer population adaptive capacity. However, most studies
explore intraspecific trait variation in systems where geographic and
environmental distances co-vary. Such a design reduces the certainty of trait
environment associations, and it is imperative for studies that make trait
environment associations be conducted in systems where environmental distance
varies independently of geographic distance. Here we explored trait variation in
such a system, and aimed to: (i) quantify trait variation of parent and offspring
generations, and associate this variation to parental environments; (ii)
determine the traits which best explain population differences; (iii) compare
parent and offspring trait-trait relationships. We characterized 15 plant
functional traits in eight populations of a shrub with a maximum separation ca.
100 km. Populations differed markedly in aridity and elevation, and environmental
distance varied independently of geographic distance. We measured traits in
parent populations collected in the field, as well as their offspring reared in
greenhouse conditions. Parent traits regularly associated with their environment.
These associations were largely lost in the offspring generation, indicating
considerable phenotypic plasticity. An ordination of parent traits showed clear
structure with strong influence of leaf area, specific leaf area, stomatal
traits, isotope delta13C and delta15N ratios, and Narea, whereas the offspring
ordination was less structured. Parent trait-trait correlations were in line with
expectations from the leaf economic spectrum. We show considerable trait
plasticity in the woody shrub over microgeographic scales (<100 km), indicating
it has the adaptive potential within a generation to functionally acclimate to a
range of abiotic conditions. Since our study shrub is commonly used for
restoration in southern Australia and local populations do not show strong
genetic differentiation in functional traits, the potential risks of transferring
seed across the broad environmental conditions are not likely to be a significant
issue.
PMID- 29942459
TI - Rarity and nutrient acquisition relationships before and after prescribed burning
in an Australian box-ironbark forest.
AB - Nutrient cycling is greatly influenced by dominant plants that contribute high
amounts of leaf litter to soils; however, less-dominant and rare species can play
keystone roles in nutrient cycling if they have unique nutrient acquisition
traits and provide high-quality litter. In many parts of the world, wildfire is
likely to become more frequent and intense under a changing climate. The effect
this will have on plant rarity and on species with unique nutrient acquisition
traits, and thus nutrient cycling, remains poorly understood. Working within an
Australian box-ironbark forest, we determined if a relationship existed between
species rarity and the uniqueness of their leaf nutrient profiles, and if this
relationship changed after prescribed burning. We created an index of species
rarity from a data set of woody perennial species abundance in areas before and
after autumn or spring burns, or left unburnt. We created indices of uniqueness
for the leaf nutrient profiles of 42 woody perennial species occurring in the
ecosystem, based on amounts of six macronutrients and four micronutrients found
in fresh and senesced leaves of each species. Five nutrient acquisition
strategies (mycorrhizal, N-fixing, carnivorous, hemiparasitic and proteoid roots)
were represented in the data set. There was no community-wide relationship
between rarity and uniqueness of leaf nutrient profiles, and this did not change
as a result of fire. However, two hemiparasitic species were relatively rare in
the ecosystem studied, and differed greatly from other species due to high K and
P in senesced leaves. Thus, some of the rarest species, such as hemiparasites,
can be functionally unique. Understanding the functional characteristics of rare
species is important so that unique functional contributors can be identified and
conserved to prevent local extinction.
PMID- 29942460
TI - Presence of fruits decreases probability of retaining flowers in a sequentially
flowering plant.
AB - Both intrinsic and extrinsic plant processes affect the fate of flowers along an
inflorescence in sequentially flowering plants. We investigated whether the
intrinsic process of competition for limited resource between fruits and flowers
owing to resource preemption or sink strength of basal fruits, or architectural
effects due to positional differences in the probability of retaining flowers,
explains a lower probability of retaining distal flowers in Yucca glauca.
Further, we investigated how the extrinsic process of seed herbivory interacts
with the plant's intrinsic processes of flower retention. We carried out a field
experiment to compare flower retention among nine combinations of three
inflorescence treatments (basal flowers only, distal flowers only, distal flowers
with presence of basal fruits) and three ovule damage treatments (no, low and
high) that serve as a cue for potential future seed herbivory. Also, we
quantified flower retention in naturally pollinated inflorescences. Experimental
results showed that the probabilities of retaining basal and distal flowers in
the absence of basal fruits were similar, thus rejecting the architectural
effects hypothesis. Further, in the presence of basal fruits that were in their
initial stages of growth, the probability of retaining distal flowers decreased,
which supports the sink strength hypothesis. We did not see an effect of ovule
damage. In naturally pollinated inflorescences, the probability of retaining
distal flowers decreased with increasing number of basal fruits. Results suggest
that basal fruits constitute strong resource sinks reducing the probability of
retaining distal flowers. Previous studies have tested this mechanism in
cultivated plants. Our study shows evidence for this mechanism in a wild flower
population.
PMID- 29942462
TI - Use of sternal plate for pectus excavatum repair in adults leads to minimal
postoperative pain.
AB - Pectus excavatum is a chest wall deformity that results in caved-in or sunken
appearance of lower half of anterior chest. Surgical treatment is favored when
functional or cosmetic concerns arise. We present a case and series of six
patients (mean haller index: 4.28) who had repair with minimal pleural disruption
and sternal plate. After a broad bilateral inframammary skin incision, the
anterior aspect of sternum is identified and incised. Next, the surgeon
hyperextends and fixates the bone in its desired position by applying manual
dorsal pressure through a small intercostal incision. Superior and inferior
fasciocutaneous flaps are raised and then advanced to reconstruct the soft tissue
defect. All patients had durable repair of the chest wall abnormalities and they
had minimal pain during the postoperative period. No analgesia medication was
necessary 1 month post-operatively. This may provide significantly less pain
compared to the Nuss or Ravitch procedures to fix Pectus excavatum.
PMID- 29942463
TI - Phosphaturic mesenchymal tumor, an unusual localization in head and neck.
AB - Phosphaturic mesenchymal tumor (PMT) is a rare mesenchymal neoplasm associated
with tumor-induced osteomalacia involving bone and soft tissue that produces
paraneoplastic hypophosphatemic osteomalacia. The common physiologic defect in
this conditions involves an impairment in renal tubular phosphate reabsorption
with a downregulation of renal 1alpha-hydroxylase activity, while calcium
metabolism remains essentially unaffected. Microscopic features consist of
spindle cells, multinucleated giant cells and calcifications embedded in a
chondromyxoid matrix with variable cellularity and prominent vascularity.
Approximately 95% of PMTs involve the extremities and appendicular skeleton, with
only 5% occurring in the head and neck region. Localization in the head and neck
is pretty uncommon, nose and paranasal sinuses are preferentially affected. Due
to its rarity, the purpose of the study was to report a new case of PMT whose
locations in temporomandibular joint was never reported in literature.
PMID- 29942464
TI - Atraumatic splenic rupture secondary to abscess in a hemodialysis patient: a rare
and fatal cause of acute abdomen diagnosed late.
AB - Splenic abscess is a very rare condition in the general population. It is more
likely to develop in association with underlying comorbidities and trauma. More
attention should be paid in patients with immunosuppression, diabetes mellitus,
and congenital or acquired immunocompromise. Splenic rupture secondary to
nontraumatic abscess causing acute abdomen is a rarer condition. Herein, we
report a 55-year-old hemodialysis patient who presented with signs and symptoms
of late generalized peritonitis. The patient was operated under emergency
conditions and diagnosed with splenic abscess rupture, for which splenectomy with
drainage procedure was performed. In such patients, the morbidity and mortality
rates vary depending on the intraoperative and postoperative risks.
PMID- 29942461
TI - Wnt/beta-catenin signalling is necessary for gut differentiation in a marine
annelid, Platynereis dumerilii.
AB - Background: Wnt/beta-catenin (or canonical) signalling pathway activity is
necessary and used independently several times for specification of vegetal fate
and endoderm, gut differentiation, maintenance of epithelium in adult intestine
and the development of gut-derived organs in various vertebrate and non
vertebrate organisms. However, its conservation in later stages of digestive
tract development still remains questionable due to the lack of detailed data,
mainly from Spiralia. Results: Here we characterize the Pdu-Tcf gene, a Tcf/LEF
orthologue and a component of Wnt/beta-catenin pathway from Platynereis
dumerilii, a spiralian, marine annelid worm. Pdu-Tcf undergoes extensive
alternative splicing in the C-terminal region of the gene generating as many as
eight mRNA isoforms some of which differ in the presence or absence of a C-clamp
domain which suggests a distinct DNA binding activity of individual protein
variants. Pdu-Tcf is broadly expressed throughout development which is indicative
of many functions. One of the most prominent domains that exhibits rather strong
Pdu-Tcf expression is in the putative precursors of endodermal gut cells which
are detected after 72 h post-fertilization (hpf). At day 5 post-fertilization
(dpf), Pdu-Tcf is expressed in the hindgut and pharynx (foregut), whereas at 7
dpf stage, it is strongly transcribed in the now-cellularized midgut for the
first time. In order to gain insight into the role of Wnt/beta-catenin
signalling, we disrupted its activity using pharmacological inhibitors between
day 5 and 7 of development. The inhibition of Wnt/beta-catenin signalling led to
the loss of midgut marker genes Subtilisin-1, Subtilisin-2, alpha-Amylase and Otx
along with a drop in beta-catenin protein levels, Axin expression in the gut and
nearly the complete loss of proliferative activity throughout the body of larva.
At the same time, a hindgut marker gene Legumain was expanded to the midgut
compartment under the same conditions. Conclusions: Our findings suggest that
high Wnt/beta-catenin signalling in the midgut might be necessary for proper
differentiation of the endoderm to an epithelium capable of secreting digestive
enzymes. Together, our data provide evidence for the role of Wnt/beta-catenin
signalling in gut differentiation in Platynereis.
PMID- 29942465
TI - Biliary pancreatitis in a duplicate gallbladder: a case report and review of
literature.
AB - Duplicated gallbladder is a rare congenital anomaly that require special
attentions due to its clinical, surgical and diagnostic difficulties. We present
a case of a 39-year-old female patient with a duplicated gallbladder who
presented with an acute biliary pancreatitis, a case to our knowledge is the
first in the literature. A double gallbladder in an abdominal ultrasonography was
doubtful, thus a computed tomography scan, a magnetic resonance
cholangiopancreatography and an endoscopic retrograde cholangiopancreatography
were done that confirmed the double gallbladder. A laparoscopic cholecystectomy
with an intraoperative cholangiography was performed safely two months after the
acute attack. The histopathological report revealed a Y-shaped type 1 double
gallbladder according to the Harlaftis et al. classification.
PMID- 29942466
TI - Gastric duplication cyst with elevated CEA level: a case report.
AB - Gastrointestinal tract duplications are congenital malformations rarely seen in
adulthood. Gastric duplications (GD) represent 2-9% of it. Malignant
transformation of GD is a rare complication described in the literature. We
present the case of a 43-year-old man, who presented an abdominal mass and an
elevated CEA level. A total gastrectomy was performed and the histological
examination described a gastric duplication cysts (GDC) without malignant
transformation. It is not the first case of elevation of CEA in GDC without
evidence of malignancy described in the literature. Some authors think that GDC
are premalignant lesions that envolve with the time to carcinomas. It is
recommend that once the GDC is diagnosed to remove surgically the entire cyst
even if the patient is asymptomatic.
PMID- 29942467
TI - Management of dermatofibrosarcoma protuberans of the face using lower trapezius
musculocutaneous pedicle flap reconstruction: a case report.
AB - Dermatofibrosarcoma protuberans (DFSP) is a rare neoplasm which represents <0.1%
of all tumors but it is considered the most common skin sarcoma. It is a slow
growing tumor that arises from the dermis and invades deeper tissues. The precise
origin of DFSP is not well known. It is most frequently seen on the trunk,
extremities, and head and neck. The standard treatment of the localized huge DFSP
consists of a wide local surgical resection with recommended surgical margins of
2-3 cm. Local recurrence after incomplete excision is common. We present a case
of 35-year-old man with enormous bulky mass on the face. Upon histological
examination, the diagnosis of DFSP was made, and the patient underwent en bloc
wide local excision of the mass followed by the use of Trapezius musculocutaneous
pedicle flap reconstruction. On 32 months follow-up, no recurrence has been
reported.
PMID- 29942468
TI - Thinking outside the rectum: a unique approach to the retrieval of gluteal
foreign bodies.
AB - Penetrating gluteal wounds with retained foreign bodies are relatively uncommon
and therefore there is no agreed-upon method of extraction. Retrieval of such
objects can be difficult to achieve due to imperfect anatomy and a lack of clear
planes across which the objects traverse, sometimes requiring novel techniques
for foreign body retrieval. We saw a 37-year-old male with a 2-month history of a
draining abscess on his right buttock. CT and manual probing of the wound
demonstrated a 5-cm tract with a possible foreign body within. We took the
patient to the operating room for exploration of the tract under general
anesthesia, allowing for palpation of the foreign object as well as digital
rectal exam, which identified an object passing posterior to the rectum. A
cystoscope was used to widen the tract and allow for better visualization.
Grasping forceps were inserted into the cystoscope and used to capture/retrieve
the object.
PMID- 29942469
TI - Gastric inlet obstruction from oesophageal cancer with internalized gastric band:
a worrisome outcome?
AB - Band erosion is one late complication of laparoscopic adjustable gastric banding
(LAGB), with the reported incidence between 1% and 28%. Far less common is
oesophageal adenocarcinoma after LAGB, with only three cases previously
described. Here we report a single case of complete gastric inlet obstruction
with oesophageal adenocarcinoma and complete internalization of a gastric band 19
years after its placement.
PMID- 29942470
TI - Extracorporeal cardiopulmonary resuscitation in a neonate after air embolism
during insufflation for laparoscopic peritoneal dialysis catheter placement.
AB - Laparoscopy is increasingly utilized in neonatal surgery with safe and effective
outcomes. Air embolism from insufflation for pneumoperitoneum is a rare but known
risk of laparoscopy. Here we present a rare case of air embolism during
insufflation for laparoscopic peritoneal dialysis catheter placement treated with
extracorporeal cardiopulmonary resuscitation.
PMID- 29942471
TI - Surgical management of iatrogenic left main coronary artery dissection.
AB - This is the case of a 40-year-old female diagnosed with NSTEMI. She underwent
coronary angiography and suffered from type F left main coronary artery
dissection. After hemodynamic stabilization, she was transferred to the nearest
cardiothoracic surgery unit and underwent emergency coronary artery bypass graft
(CABG) surgery. This report highlights important concepts in the management of a
rare complication and emphasizes the surgical treatment decision-making,
underlying an unusual but effective treatment approach.
PMID- 29942472
TI - Enlargement of papillary glioneuronal tumor in an adult after a follow-up period
of 10 years: a case report.
AB - Papillary glioneuronal tumor (PGNT) is a rare brain tumor grouped under mixed
glioneuronal tumors according to the World Health Organization Classification of
the Central Nervous System. The natural history of this pathology is not yet well
documented. We report a case of PGNT that increased in size after a follow-up
period of 10 years. An enlarged cyst wall and nodule showed a low intensity
signal on T2*-weighted, suggesting hemorrhage during the clinical course.
Characteristic pathological findings along with absence of BRAFV600E mutation
identified the tumor as PGNT. The tumor characteristics of PGNT are discussed
based on the presented case, with reference to the existing literature.
PMID- 29942473
TI - Cecal ameboma mimicking obstructing colonic carcinoma.
AB - Ameboma is a mass of granulation tissue with peripheral fibrosis and a core of
inflammation related to amebic chronic infection. The initial presentations of
colonic ameboma usually include obstruction and low gastrointestinal bleeding. It
may mimic colon carcinoma or other granulomatous inflammatory conditions of the
colon in both the clinical presentation and the endoscopic appearance. Here, we
report a case of a 45-year-old male with a presentation of abdominal pain and
constipation, as well as clinical, radiological and endoscopic presentation
resembling colonic carcinoma, that was managed operatively with right
hemicolectomy and post-operative histopathologic finding of cecal ameboma.
PMID- 29942474
TI - Benign inverted papilloma at bladder neck causing acute urinary retention.
AB - Inverted papilloma of the urinary tract is a rare benign lesion. A 59-year-old
male who presented with the chief complaint of gross hematuria and acute urinary
retention is described. Cystoscopy revealed a solitary, papillary tumor at the
bladder neck. Transurethral resection was performed, and histological examination
revealed a pathological diagnosis of inverted papilloma. Following resection, the
patient was able to void without difficulty. This is an interesting case of acute
urinary retention secondary to an inverted papilloma at the bladder neck causing
intermittent outlet obstruction, and we review the literature on inverted
papilloma of the bladder.
PMID- 29942475
TI - Irreversible electroporation in borderline resectable pancreatic adenocarcinoma
for margin accentuation.
AB - Achieving clear microscopic resection margins following pancreaticoduodenectomy
(PD) is challenging particularly in borderline resectable pancreatic carcinoma
(BRPC). Positive resection margins has been identified as a major independent
prognostic factor. Irreversible electroporation (IRE) has emerged as a promising
non-thermal ablative method that could be used in the treatment of pancreatic
cancer as an adjunct to chemotherapy and surgery. This case report describes the
successful simultaneous intraoperative IRE and PD in a patient with BRPC,
achieving clear microscopic resection margins. Technical aspects and histology
showing the effect of IRE are presented. The role of IRE in the treatment of
pancreatic adenocarcinoma should be further evaluated in prospective studies.
PMID- 29942476
TI - A case of ectopic liver tissue adherent to the gallbladder.
AB - We report a case of a 30-year-old lady who presented to the emergency department
with a 1 day history of severe epigastric pain which radiated to the back.
Focused history, physical exam findings, haematological and radiological
investigations, including ultrasound scanning of the abdomen, supported the
diagnosis of acute gallstone pancreatitis. She was managed conservatively and
underwent elective laparoscopic cholecystectomy at a later date.
Intraoperatively, there was noted to be a small nodule loosely adherent to the
gallbladder serosa. Histology from this nodule revealed it to be a portion of
anatomically normal liver parenchyma also referred to as ectopic liver tissue
(ELT). ELT is a rare developmental abnormality in which normally functioning
liver tissue develops at an extra-hepatic site. ELT is known to have an increased
risk of neoplastic transformation and so we believe it to be of clinical
importance.
PMID- 29942477
TI - Spontaneous adrenal hemorrhage. Report of two cases and review of pathogenesis,
diagnosis and management.
AB - Adrenal hemorrhage represents a relatively rare condition, usually associated
with meningococcal septicemia. It is an underestimated cause of acute
decompensation, multiorgan failure and death, usually diagnosed post-mortem.
Depending on its etiology adrenal hemorrhage is categorized as traumatic and non
traumatic. The technical advancement of imaging modalities, has made diagnosis
and management more efficient. Assessment of hemodynamic stability, exclusion of
a hormonal active adrenal tumor and assessment for adrenal insuffi!ciency, are of
cardinal importance. Angiographic embolization has contributed significantly in
better outcomes as emergency laparotomy is associated with high morbidity and
mortality rates. Hereby we present two cases of spontaneous adrenal hemorrhage
associated with extensive retroperitoneal bleeding and hemodynamic instability.
Both underwent angiography with one requiring embolization with favorable
outcome. Investigation for exclusion of underlying adrenal tumor, adrenal
insufficiency and follow-up imaging are presented in detail for both cases.
PMID- 29942478
TI - Diagnosis of human immunodeficiency virus following femoral head harvest post
total hip arthroplasty.
AB - Elective total hip arthroplasty (THA) is a routine procedure. Intraoperative
harvesting of excised femoral heads for the purpose of donation during this
procedure has become standard practice, in response to increasing bone allograft
demand. Robust patient screening and femoral head analysis typically occurs, to
minimize the risk of disease transmission to any potential recipient. Screening
for human immunodeficiency virus (HIV), a virus normally first diagnosed through
serological testing, makes up part of this process. This case describes a 43-year
old male who underwent elective THA, with subsequent analysis of the excised
femoral head at time of screening revealing a diagnosis of HIV, a condition
previously never detected in the donor. First diagnosis of HIV from bone is
exceedingly rare, with this case illustrating an unusual diagnostic pathway of a
well-understood condition, as well as representing an unfamiliar outcome
following a common surgical intervention.
PMID- 29942479
TI - Burkitt's lymphoma presenting as acute appendicitis: a case report.
AB - Appendiceal lymphomas are exceedingly rare, constituting around 0.015% of all
gastrointestinal lymphoma cases. Burkitt's lymphoma is the second most prevalent
pathology, diagnosed in 25.9% of patients. We report a case of a 36-year-old male
admitted with acute abdominal pain with 2 days of evolution, localized in the
right lower quadrant associated with hyporexia, but no fever. On examination he
presented abdominal tenderness on the right iliac fossa. A diagnosis of acute
appendicitis was made clinically. At the post-operative follow up, 2 weeks later,
he presented a low back pain of high intensity, associated with swelling of the
abdomen, night sweats, daily fevers and weight loss. The histopathological exam
of the appendix revealed diffuse and transmural lymphoid proliferation.
Immunohistochemistry suggested high grade B-cell lymphoma indicative of Burkitt's
lymphoma. This patient was staged as a IVxB lymphoma and was submitted into
polychemotherapy with a complete clinical response in 8 months.
PMID- 29942480
TI - Acute single appendicitis in a female with a duplicated appendix.
AB - Appendiceal duplication is a rare congenital anomaly with an estimated incidence
ranging from 0.004 to 0.009%. Preoperative diagnosis of a duplicated appendix is
often difficult and is usually done intraoperatively. Histopathological
examination of the surgical specimen is mandatory to confirm the presence of two
appendices. In this case we report a female patient with acute inflammation in
one of her two appendices. Surgeons should always bear in mind this rare anomaly
to avoid serious ethical and legal consequences.
PMID- 29942481
TI - Unique surgical approach to a twisted ileal-anal pouch.
AB - Total proctocolectomy with ileal pouch-anal anastomosis can restore
gastrointestinal continuity in patients requiring colectomy for ulcerative
colitis, however, it can be associated with high morbidity. Reoperation for pouch
related complications is technically challenging and often leads to deterioration
of pouch function or need for permanent stoma. We report a case of acute on
chronic small bowel obstruction secondary to a 360-degree twist in the small
bowel introduced during creation of the ileal-anal pouch. Our novel approach at
repair has not been reported in past literature which included resection and re
anastomosis of the small bowel proximal to the pouch allowing for pouch salvage
with return to function.
PMID- 29942482
TI - Delayed central nervous system manifestation of Chikungunya virus with magnetic
resonance T2 weighted imaging high signal changes-a case report.
AB - CHIKV is a relatively new virus and we are still learning about the illness. Very
little is known about CNS its involvement and even less about its delayed or long
term manifestations if any. It therefore behoves us to consider delayed CNS
involvement when assessing patients with CHIKV infections that may not have had
an acute neurological manifestation at the time of diagnosis coupled with new
onset neurological manifestations and MRI abnormalities. It seems likely that
patients with CHIKV may experience delayed CNS manifestation of the viral
infection. This report highlights the importance of a travel history when
assessing patients with a neurological complaint. The pathway to best manage such
cases is with repeated imaging to assess if the signal changes either progress,
resolve or more importantly if there is any MRI correlation should changes in
neurology develop during the surveillance period.
PMID- 29942483
TI - Triple thrombophilic simultaneous mutations in patients after bariatric surgery:
is there a role for screening in the Eastern Mediterranean?
AB - BACKGROUND AND PURPOSE: Thrombophilia is a hypercoagulable state that predisposes
to thrombosis. Several genetic risk factors have been shown to predispose to
thromboembolic events. Homozygosity to a thrombophilic mutation certainly
predisposes the affected patient to more serious symptoms. MATERIALS AND METHODS:
Here we present a case of a 56-year-old male patient who underwent sleeve
gastrectomy for morbid obesity, presenting to our institution with abdominal
pain. Investigations revealed thrombosis of the splenic, axillary vein as well as
the right pulmonary artery. The patient was found to have triple thrombophilic
mutations. RESULTS: To our knowledge, this is the first reported case of three
specific simultaneous thrombophilic mutations in a patient from the Eastern
Middle East. CONCLUSION: We suggest a role for screening for thrombophilic
mutations in the Eastern Mediterranean patients undergoing bariatric surgeries
for morbid obesity due to the increased risk of thrombosis in this group of
patients.
PMID- 29942484
TI - Acute-right-ventricular-failure post-cardiotomy: RVAD as a bridge to a successful
recovery.
AB - This is the case of a 57-year-old woman who underwent coronary-artery-bypass
grafting following a diagnosis of NSTEMI with triple-coronary-vessel-disease.
During separation from cardiopulmonary-bypass she developed acute severe-right
ventricular-failure refractory to inotropic support and intra-aortic-balloon-pump
counterpulsation. Therefore VA-ECMO was established in order to separate the
patient from cardiopulmonary-bypass. VA-ECMO was then transitioned to RVAD
support which allowed complete recovery of RV-function and subsequent
explantation. The patient was eventually discharged home.
PMID- 29942485
TI - Disseminated Mycobacterium abscessus infection with spondylodiscitis of thoracic
spine.
AB - A case is presented of an immunosuppressed 51-year-old man with spondylodiscitis
of the thoracic vertebrae from Mycobacterium abscessus infection, in context of
disseminated multi-systemic infection with pulmonary and gastrointestinal
involvement. Multiple challenges in the diagnosis and management of this
confounding case are outlined. The patient underwent aggressive surgical
debridement via T8-T10 vertebrectomy plus reconstruction, and right hemicolectomy
to obtain source control. This was followed by prolonged combination antibiotic
therapy. At time of manuscript patient is 10 months post-surgery and 18 months
from initial presentation, with excellent surgical outcome and control of the
infection. The unique microbiological and clinical characteristics of M.
abscessus are briefly outlined. A synopsis of the relevant literature is given
highlighting the relative paucity of evidence to aid management of this
unpredictable infection. Current best practice guideline recommends combination
of medical therapy and aggressive surgical debridement for infections caused by
M. abscessus.
PMID- 29942486
TI - Fever of unknown origin: a rare presentation of giant hepatic hemangioma.
AB - Hepatic hemangioma is mostly asymptomatic and incidental finding on imaging.
Fever of unknown origin as a sole presentation is rare. We present an interesting
case report of a 49-year-old female, who presented with fever for three months.
Extensive blood investigations and infectious workup failed to reveal the cause.
Contrast computed tomography of abdomen revealed a giant (15 * 11 cm) hemangioma
arising from left lateral segment of liver, and was attributed as a cause for
fever. Surgical excision of hemangioma completely ameliorated the fever.
PMID- 29942487
TI - Aspirin inhibited the metastasis of colon cancer cells by inhibiting the
expression of toll-like receptor 4.
PMID- 29942488
TI - Tonsillar cytokine expression between patients with tonsillar hypertrophy and
recurrent tonsillitis.
AB - Background: Tonsils provide an innovative in vivo model for investigating immune
response to infections and allergens. However, data are scarce on the differences
in tonsillar virus infections and immune responses between patients with
tonsillar hypertrophy or recurrent tonsillitis. We investigated the differences
in virus detection and T cell and interferon gene expression in patients
undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis.
Methods: Tonsils of 89 surgical patients with tonsillar hypertrophy (n = 47) or
recurrent tonsillitis (n = 42) were analysed. Patients were carefully
characterized clinically. Standard questionnaire was used to asses preceding and
allergy symptoms. Respiratory viruses were analysed in tonsils and nasopharynx by
PCR. Quantitative real-time PCR was used to analyse intratonsillar gene
expressions of IFN-alpha, IFN-beta, IFN-gamma, IL-10, IL-13, IL-17, IL-28, IL-29,
IL-37, TGF-beta, FOXP3, GATA3, RORC2 and Tbet. Results: Median age of the
subjects was 15 years (range 2-60). Patients with tonsillar hypertrophy were
younger, smoked less often, had less pollen allergy and had more adenovirus,
bocavirus-1, coronavirus and rhinovirus in nasopharynx (all P < 0.05). Only
bocavirus-1 was more often detected in hypertrophic tonsils (P < 0.05). In age
adjusted analysis, tonsillar hypertrophy was associated with higher mRNA
expressions of IL-37 (P < 0.05). Conclusions: Intratonsillar T cell and
interferon gene expressions appeared to be relatively stable for both tonsillar
hypertrophy and recurrent tonsillitis. Of the studied cytokines, only newly
discovered anti-inflammatory cytokine IL-37, was independently associated with
tonsillar hypertrophy showing slightly stronger anti-inflammatory response in
these patients.
PMID- 28815017
TI - Autophagy and airway fibrosis: Is there a link?
AB - In the past decade, an emerging process named "autophagy" has generated intense
interest in many chronic lung diseases. Tissue remodeling and fibrosis is a
common feature of many airway diseases, and current therapies do not prevent or
reverse these structural changes. Autophagy has evolved as a conserved process
for bulk degradation and recycling of cytoplasmic components to maintain basal
cellular homeostasis and healthy organelle populations in the cell. Furthermore,
autophagy serves as a cell survival mechanism and can also be induced by chemical
and physical stress to the cell. Accumulating evidence demonstrates that
autophagy plays an essential role in vital cellular processes, including tissue
remodeling. This review will discuss some of the recent advancements made in
understanding the role of this fundamental process in airway fibrosis with
emphasis on airway remodeling, and how autophagy can be exploited as a target for
airway remodeling in asthma and chronic obstructive pulmonary disease.
PMID- 29152223
TI - Stage 1 Registered Report: Effect of deficient phagocytosis on neuronal survival
and neurological outcome after temporary middle cerebral artery occlusion
(tMCAo).
AB - Stroke is a major cause of death and disability worldwide. In addition to
neuronal death resulting directly from energy depletion due to lack of blood
supply, inflammation and microglial activation following ischemic brain injury
has been increasingly recognized to be a key contributor to the pathophysiology
of cerebrovascular disease. However, our understanding of the cross talk between
the ischemic brain and the immune system is limited. Recently, we demonstrated
that following focal ischemia, death of mature viable neurons can be executed
through phagocytosis by microglial cells or recruited macrophages, i.e. through
phagoptosis. It was shown that inhibition of phagocytic signaling pathways
following endothelin-1 induced focal cerebral ischemia leads to increased
neuronal survival and neurological recovery. This suggests that inhibition of
specific phagocytic pathways may prevent neuronal death during cerebral ischemia.
To further explore this potential therapeutic target, we propose to assess the
role of phagocytosis in an established model of temporary (45min) middle cerebral
artery occlusion (tMCAo), and to evaluate neuronal survival and neurological
recovery in mice with deficient phagocytosis. The primary outcome of this study
will be forelimb function assessed with the staircase test. Secondary outcomes
constitute Rotarod performance, stroke volume (quantified on MR imaging or brain
sections, respectively), diffusion tensor imaging (DTI) connectome mapping, and
histological analyses to measure neuronal and microglial densities, and
phagocytic activity. Male mice aged 10-12 weeks will be used for experiments.
PMID- 29904591
TI - Predicting ionizing radiation exposure using biochemically-inspired genomic
machine learning.
AB - Background: Gene signatures derived from transcriptomic data using machine
learning methods have shown promise for biodosimetry testing. These signatures
may not be sufficiently robust for large scale testing, as their performance has
not been adequately validated on external, independent datasets. The present
study develops human and murine signatures with biochemically-inspired machine
learning that are strictly validated using k-fold and traditional approaches.
Methods: Gene Expression Omnibus (GEO) datasets of exposed human and murine
lymphocytes were preprocessed via nearest neighbor imputation and expression of
genes implicated in the literature to be responsive to radiation exposure (n=998)
were then ranked by Minimum Redundancy Maximum Relevance (mRMR). Optimal
signatures were derived by backward, complete, and forward sequential feature
selection using Support Vector Machines (SVM), and validated using k-fold or
traditional validation on independent datasets. Results: The best human
signatures we derived exhibit k-fold validation accuracies of up to 98% ( DDB2,
PRKDC, TPP2, PTPRE, and GADD45A) when validated over 209 samples and traditional
validation accuracies of up to 92% ( DDB2, CD8A, TALDO1, PCNA, EIF4G2, LCN2,
CDKN1A, PRKCH, ENO1, and PPM1D) when validated over 85 samples. Some human
signatures are specific enough to differentiate between chemotherapy and
radiotherapy. Certain multi-class murine signatures have sufficient granularity
in dose estimation to inform eligibility for cytokine therapy (assuming these
signatures could be translated to humans). We compiled a list of the most
frequently appearing genes in the top 20 human and mouse signatures. More
frequently appearing genes among an ensemble of signatures may indicate greater
impact of these genes on the performance of individual signatures. Several genes
in the signatures we derived are present in previously proposed signatures.
Conclusions: Gene signatures for ionizing radiation exposure derived by machine
learning have low error rates in externally validated, independent datasets, and
exhibit high specificity and granularity for dose estimation.
PMID- 29942492
TI - Epidemiology of carbapenem-resistant Klebsiella pneumoniae bloodstream infections
after renal transplantation from donation after cardiac death in a Chinese
hospital: a case series analysis.
AB - Background: Although the high mortality rates have been extensively reported
worldwide, few studies have investigated the epidemiology of CRKP-BSIs in the
early stage after kidney transplantation (KTx) from donation after cardiac death
(DCD). We sought to describe the epidemiological and clinical characteristics of
cases of carbapenem resistant Klebsiella pneumoniae bloodstream infections (CRKP
BSIs) in kidney transplantation recipients (KTRs) from DCD in our hospital.
Methods: A retrospective analysis of clinical data of CRKP-BSIs in KTRs admitted
to a Chinese hospital in Beijing, China, between January 1, 2012 and December 31,
2016 was performed. The annual percentage of patients with CRKP, the annual
number of total KTRs and KTRs from DCD were determined. The genetic relatedness
of the strains was determined by polymerase chain reaction and pulse field gel
electrophoresis (PFGE). Results: During the study period, there were total 947
KTRs in our hospital, including 275 KTRs from DCD. Five incidences of CRKP-BSIs
in KTRs were identified, and two of them (Case 1,3) from the same foreign
hospital. The incidence of CRKP-BSIs in the early stage (within 3 months)
following kidney transplantation (KTx) from DCD was about 1.1% (3/275). In Case 1
3 and 5, the rupture of renal transplant artery was presented on the 40th, 16th,
43th and 74th day after KTx, and in Case 4, the thrombus of renal transplant
artery was presented on the 13th day after KTx. Three cases (Case 1,2,5)
occurring pneumothorax on the 45th, 51th and 32th day after KTx. Four cases (Case
1-4) received the excision of the transplanted kidney for the treatment.
Polymerase chain reaction showed the bands for case 2 were distinctive from other
cases. Pulse field gel electrophoresis showed mainly three clusters of the bands
for all the isolates. Conclusions: During the study period, we observed an
increase in the occurrence of CRKP-BSIs among KTRs from DCD in our hospital. We
demonstrated that rupture/thrombus of the renal transplant artery was associated
with CRKP-BSI in the early stage after KTx from DCD. Albeit the low incidence of
CRKP-BSI (1.1%) after KTx from DCD, the high mortality (4/5) had been observed
from the prognosis of the patients. Thorough surveillance of DCD donors, early
identification of CRKP-BSI, necessary preventative measurements and use of
appropriate treatments should be the strategy for CRKP-BSI in the early stage
after KTx from DCD.
PMID- 29942493
TI - Clinical and diagnostic features of Bartter and Gitelman syndromes.
AB - Background: Bartter and Gitelman syndromes are autosomal recessive disorders of
renal tubular salt handling. Due to their rarity, limited long-term data are
available to inform prognosis and management. Methods: Long-term longitudinal
data were analysed for 45 children with pathogenic variants in SLC12A1 (n = 8),
KCNJ1 (n = 8), CLCNKB (n = 17), BSND (n = 2) and SLC12A3 (n = 10) seen at a
single centre between 1984 and 2014. Median follow-up was 8.9 [interquartile
range (IQR) 0.7-18.1] years. Results: Polyhydramnios and prematurity were seen in
children with SLC12A1 and KCNJ1 mutations. Patients with CLCNKB mutations had the
lowest serum potassium and serum magnesium and the highest serum bicarbonate
levels. Fractional excretion of chloride was >0.5% in all patients prior to
supplementation. Nephrocalcinosis at presentation was present in the majority of
patients with SLC12A1 and KCNJ1 mutations, while it was only present in one
patient with CLCNKB and not in SLC12A3 or BSND mutations. Growth was impaired,
but within the normal range (median height standard deviation score -1.2 at the
last follow-up). Impaired estimated glomerular filtration rate (eGFR <90
mL/min/1.73 m2) at the last follow-up was seen predominantly with SLC12A1 [71
mL/min/1.73 m2 (IQR 46-74)] and KCNJ1 [62 mL/min/1.73 m2 (IQR 48-72)] mutations.
Pathological albuminuria was detected in 31/45 children. Conclusions: Patients
with Bartter and Gitelman syndromes had a satisfactory prognosis during
childhood. However, decreased eGFR and pathologic proteinuria was evident in a
large number of these patients, highlighting the need to monitor glomerular as
well as tubular function. Electrolyte abnormalities were most severe in CLCNKB
mutations both at presentation and during follow-up. Fractional excretion of
chloride prior to supplementation is a useful screening investigation in children
with hypokalaemic alkalosis to establish renal salt wasting.
PMID- 29942494
TI - Renal thrombotic microangiopathy and pulmonary arterial hypertension in a patient
with late-onset cobalamin C deficiency.
AB - Cobalamin C (cblC) deficiency is the most commonly inherited inborn error of
vitamin B12 metabolism. It is characterized by multisystem involvement with
severe neurological, hematological, renal and cardiopulmonary manifestations.
Disease is most commonly diagnosed early in the first decade of life. We report a
case of a 20-year-old woman who developed severe pulmonary arterial hypertension
while under nephrologic follow-up for chronic kidney disease. She had initially
presented at 14 years of age with visual disturbance and acute renal failure and
been diagnosed with thrombotic thrombocytopenic purpura on the basis of kidney
biopsy findings of thrombotic microangiopathy and compatible ADAMTS13 (a
disentegrin and metalloproteinase with a thrombospondin type 1 motif member 13).
When cblC deficiency was eventually diagnosed, remarkable improvement in
cardiopulmonary function was evident upon initiation of treatment. This case
highlights the importance of a timely diagnosis and initiation of treatment for
cblC deficiency. Clinical diagnosis may be challenged by asynchronous organ
symptom presentation and by misleading laboratory tests, in this case: an initial
low ADAMTS13. A simple test of plasma homocysteine level should be encouraged in
cases of thrombotic microangiopathy and/or pulmonary artery hypertension.
PMID- 29942497
TI - Clinical and pathological characteristics of non-diabetic renal disease in type 2
diabetes patients.
AB - Background: Renal involvement in type 2 diabetes is mainly due to diabetic
nephropathy (DN). Nevertheless, a sizable proportion of diabetic patients could
actually have nondiabetic renal diseases (NDRDs) or DN plus NDRDs. This study
aimed to explore the pathological features of NDRD in diabetic patients and to
assess the predictability of diagnosing NDRD (+/-DN) versus isolated DN on the
basis of clinical parameters. Methods: Medical records of type 2 diabetes
patients who underwent renal biopsy under suspicion of NDRD from January 2011
through November 2015 were analyzed retrospectively. Results: A total of 101
patients were enrolled in this study. The most frequent indication for renal
biopsy was recent onset of nephrotic syndrome (41%), followed by rapidly
progressive renal failure (29%) and active urinary sediment (21%). On renal
biopsy, 51% of patients had isolated DN, 20% had isolated NDRD and 29% had DN
plus NDRD. IgA nephropathy was the most common cause of isolated NDRD, whereas
acute tubular necrosis (39%) and acute interstitial nephritis (33%) were the main
causes of NDRD superimposed on DN. Male gender, short-duration diabetes (<8
years), lower glycated hemoglobin and active urinary sediment (>=10 red and white
blood cells per high-power field) were independent predictors of NDRD according
to multiple logistic regression analysis. Conclusions: Judicious use of renal
biopsy revealed NDRD (+/-DN) in nearly half of type 2 diabetes patients with
atypical renal presentation, especially in male patients with well-controlled
diabetes, those who have had diabetes for a short duration and those with active
urinary sediment.
PMID- 29942496
TI - Low-dose Rituximab therapy in resistant idiopathic membranous nephropathy: single
center experience.
AB - Background: Persistent significant proteinuria has been associated with increased
risk of progression to end-stage kidney disease in patients with idiopathic
membranous nephropathy (IMN). Rituximab (RTX) therapy has given encouraging
results in IMN, but most of the studies have used a higher dose, which is limited
by the high cost as well as a potential increased risk of infections. Our study
aimed to assess the efficacy and safety of low-dose RTX in patients with
immunosuppression-resistant IMN. Methods: A total of 21 patients with treatment
resistant IMN treated with RTX from 2015 to 2016 at our center were included in
the study. They received two doses of RTX (500 mg each) infusion 7 days apart.
CD19 count was performed after 4 weeks. A single dose of RTX was repeated after 4
6 weeks if CD19 count was not depleted. Results: The mean standard deviation age
of patients was 33.3 +/- 12.3 years and 33.3% were females. Mean proteinuria
before RTX therapy was 6.2 +/- 2.2 g/day, serum creatinine was 0.9 +/- 0.3 mg/dL
and estimated glomerular filtration rate (eGFR) was 95.8 +/- 26.9 mL/min/1.73 m2.
All the patients were non-responders to prior immunosuppressive treatment. Twenty
(95.2%) patients achieved targeted CD19 depletion with two doses of RTX. One
patient required one additional RTX dose due to inadequate B-cell suppression. A
total of 13 (61.9%) patients achieved remission with RTX therapy: 4 (19.0%)
complete and 9 (42.9%) partial remission. Patients who did not respond to RTX had
a significantly lower baseline eGFR compared with those who achieved remission (P
= 0.022). One patient developed respiratory tract infection following RTX during
the follow-up, which responded to a course of oral antibiotics. During median
follow-up of 13.1 (10-23.9) months, four (19%) patients had deterioration in
renal function and one patient relapsed after achieving partial remission. Renal
survival was significantly better in patients who responded to RTX therapy as
compared with those who did not achieve remission (P = 0.0037). Conclusion: Low
dose RTX therapy is effective and safe in immunosuppression-resistant IMN.
PMID- 29942498
TI - Clinical profile and outcome of pigment-induced nephropathy.
AB - Background: Pigment nephropathy represents one of the most severe complications
of rhabdomyolysis or hemolysis. Methods: We performed a retrospective
observational study to analyze the etiology, clinical manifestation, laboratory
profile and outcome in patients with biopsy-proven pigment-induced nephropathy
between January 2011 and December 2016. History, clinical examination findings,
laboratory investigations and outcome were recorded. Results: A total of 46
patients were included with mean follow-up of 14 +/- 5.5 months. Mean age was
40.15 +/- 12.3 years, 65% were males (male:female, 1.8:1) and ~37 (80.4%) had
oliguria. Mean serum creatinine at presentation and peak creatinine were 7.5 +/-
2.2 and 12.1 +/- 4.3 mg/dL, respectively. Evidence of rhabdomyolysis was noted in
26 patients (64%) and hemolysis in 20 patients (36%). Etiology of rhabdomyolysis
include snake envenomation (10 patients), seizures (7), strenuous exercise (5),
wasp sting (2) and rifampicin induced (2). The causes of hemolysis include
rifampicin induced (7 patients), sepsis (5), malaria (3), mismatched blood
transfusion/transfusion reaction (3) and paroxysmal nocturnal hemoglobinuria (2).
On renal biopsy, two patients had acute interstitial nephritis and two had
immunoglobulin A deposits in addition to pigment nephropathy. All except one
(97.8%) required hemodialysis (HD) during hospital stay and mean number of HD
sessions was 9 +/- 2. A total of three patients with sepsis/disseminated
intravascular coagulation died, all had associated hemolysis. On statistical
analysis, there was no difference between AKI due to rhabdomyolysis and hemolysis
except for high creatine phosphokinase in patients with rhabdomyolysis and
Lactate dehydrogenase level in patients with hemolysis. At mean follow-up, five
patients (12%) progressed to chronic kidney disease (CKD). Conclusions: Pigment
nephropathy due to rhabdomyolysis and hemolysis is an important cause of renal
failure requiring HD. The prognosis was relatively good and depends on the
etiology; however, long-term studies and follow-up are needed to assess the true
incidence of CKD due to pigment nephropathy.
PMID- 29942495
TI - Risk factors associated with post-kidney transplant malignancies: an article from
the Cancer-Kidney International Network.
AB - In kidney transplant recipients, cancer is one of the leading causes of death
with a functioning graft beyond the first year of kidney transplantation, and
malignancies account for 8-10% of all deaths in the USA (2.6 deaths/1000 patient
years) and exceed 30% of deaths in Australia (5/1000 patient-years) in kidney
transplant recipients. Patient-, transplant- and medication-related factors
contribute to the increased cancer risk following kidney transplantation. While
it is well established that the overall immunosuppressive dose is associated with
an increased risk for cancer following transplantation, the contributive effect
of different immunosuppressive agents is not well established. In this review we
will discuss the different risk factors for malignancies after kidney
transplantation.
PMID- 29942499
TI - Is progression of coronary artery calcification influenced by modality of renal
replacement therapy? A systematic review.
AB - Background: Progression of coronary artery calcification is an important marker
for cardiovascular morbidity in end-stage renal disease patients. Therefore, we
reviewed the evidence on coronary artery calcification progression in different
renal replacement therapies. Methods: MEDLINE (PubMed), Embase and TRIP databases
were searched from 1999 - 2016. Additionally, bibliographies were searched by
hand and citation tracking of key publications was performed. Prospective studies
were included that examined coronary artery calcification with two or more
multislice computed tomography scans >=6 months apart in patients 18-75 years old
receiving any renal replacement therapy, including kidney transplantation.
Reporting of separate scores for different modalities was required. Two
researchers extracted data independently with pilot-tested forms and assessed the
risk of bias using a validated tool. Results: We identified 29 eligible studies
that assessed coronary artery calcification progression in end-stage renal
disease patients, of which 19 studies evaluated haemodialysis and 8 kidney
transplantation. Evidence on progression in peritoneal dialysis (three studies)
and nocturnal haemodialysis (one study) was limited. Meta-analysis was not
possible due to diverse reporting methods of coronary artery calcification scores
and definitions of progression. Median coronary artery calcification scores were
considerably higher in haemodialysis cohorts at baseline, presumably due to a
generally higher age and dialysis vintage. Median coronary artery calcification
progressed universally. Visual inspection suggested the least progression in
kidney transplant recipients. Conclusions: There is insufficient evidence to
compare the influence of renal replacement therapies on coronary artery
calcification progression. We advocate the adoption of a standardized reporting
method of coronary artery calcification progression.
PMID- 29942500
TI - Shock-wave lithotripsy or ureterorenoscopy for renal stones?
AB - Kidney stones are a common condition with high direct and indirect costs; to
date, the optimal urological approach for some particular presentations including
non-lower pole kidney stones between 10 and 20 mm of diameter is not clear. A
limited number of randomized controlled trials and observational longitudinal
studies suggests that ureterorenoscopy (URS) could be superior to shock-wave
lithotripsy (SWL) in achieving stone-free rates in this setting; however, such
reports are generally weakened by a number of limitations including small sample
size and scarce control for confounding. In this issue, Fankhauser et al. [1]
report the results of a large observational retrospective study on the
comparative efficacy and safety of URS and SWL for the treatment of previously
untreated kidney stones.
PMID- 29942501
TI - Is relative overhydration measurement by bioimpedance spectroscopy useful in
reducing morbidity and mortality in chronic kidney disease?
AB - It is well known that one of the main determinants of mortality and morbidity in
chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients is fluid
overload acting on the cardiovascular system causing hypertension, increased
arterial stiffness, left ventricular hypertrophy and eventually heart failure.
Therefore, assessment and management of volume status is crucial. Bioimpedance
spectroscopy is one of the most popular and practical methods for volume
evaluation. Volume evaluation should be a routine part of following CKD and ESRD
patients, in order to decrease associated mortality and morbidity.
PMID- 29942502
TI - Any grade of relative overhydration is associated with long-term mortality in
patients with Stages 4 and 5 non-dialysis chronic kidney disease.
AB - Background: Overhydration (OH) is associated with mortality in chronic kidney
disease (CKD). A relative overhydration adjusted for extracellular water (OH/ECW)
measured by bioimpedance >15% has shown an increased mortality risk in
haemodialysis but few studies have been developed in advanced CKD. Our objective
was to evaluate the effect of OH on mortality in patients with Stage 4 or 5 non
dialysis CKD. Methods: We performed a prospective study of 356 patients enrolled
in 2011 and followed up until 2016. At baseline we collected general
characteristics, serum inflammatory and nutrition markers, cardiovascular events
(CVEs) and body composition using bioimpedance spectroscopy. During a median
follow-up of 50 (24-66) months we collected mortality data. Results: The mean
creatinine was 3.5 +/- 1.3 mg/dL, median proteinuria was 0.5 [interquartile range
(IQR) 0.2-1.5] g/24 h, median OH was 0.6 (IQR -0.4-1.5) L and mean relative OH
(OH/ECW) was 2.3 +/- 0.8%. We found that 32% of patients died. The univariate Cox
analysis showed an association between mortality and age, diabetes, previous
CVEs, Charlson comorbidity index, low albumin and pre-albumin, high C-reactive
protein (CRP), low lean tissue and high OH/ECW. Multivariate Cox analysis
confirmed an association between mortality and age {exp(B) 1.1 [95% confidence
interval (CI) 1.0-1.3]; P = 0.001}, Charlson comorbidity index [exp(B) 1.1 (95%
CI 1.0-1.2); P = 0.01], CRP [exp(B) 1.1 (95% CI 1.0-1.2); P = 0.04], OH/ECW
[exp(B) 3.18 (95% CI 2.09-4.97); P = 0.031] and low lean tissue [exp(B) 0.82 (95%
CI 0.69-0.98); P = 0.002]. Kaplan-Meier analysis confirmed higher mortality in
patients with OH/ECW >0% (log rank 11.1; P = 0.001). Conclusion: Any grade of
relative OH measured by OH/ECW >0% is associated with long-term mortality in
patients with Stage 4 or 5 non-dialysis CKD.
PMID- 29942503
TI - Relations of established aging biomarkers (IL-6, D-dimer, s-VCAM) to glomerular
filtration rate and mortality in community-dwelling elderly adults.
AB - Background: Biomarkers improving risk prediction for elderly populations with
chronic kidney disease (CKD), an independent predictor of mortality, could be
particularly useful. We previously observed that interleukin-6 (IL-6), D-dimer
and soluble vascular adhesion molecule (s-VCAM) were independent biomarkers of
mortality in elderly individuals. Therefore, we investigated whether these
established biomarkers were independently associated with both estimated
glomerular filtration rate (eGFR) and mortality. Methods: The Established
Populations for Epidemiologic Studies of the Elderly (EPESE) is a longitudinal
cohort of community-dwelling elderly individuals. We investigated the association
among eGFR, the biomarkers (IL-6, D-dimer and s-VCAM) and 4-year all-cause
mortality using restricted cubic splines within Cox proportional hazards models.
Results: Among 1907 participants in EPESE, 1342 had available creatinine and
biomarker measures. Incidence of all-cause mortality was 21.6%. eGFR was
associated with all-cause mortality (P < 0.01); individuals at the lowest (<30
mL/min/1.73 m2) levels had the highest mortality rates. D-dimer and s-VCAM were
associated (P < 0.01) with mortality, and after adjustment for IL-6, D-dimer and
s-VCAM, the mortality risk varied by eGFR level. Conclusions: In community
dwelling elderly individuals, we observed an association among eGFR, 4-year
mortality and IL-6, D-dimer and s-VCAM. eGFR was independently associated with
mortality, and the relation between eGFR and mortality was modified by IL-6, D
dimer and s-VCAM, which was most notable in individuals with severely reduced
eGFR. These findings suggest that IL-6, D-dimer and s-VCAM may be useful
biomarkers for improving risk prediction, but further studies are needed
examining the role of these biomarkers in elderly individuals with CKD.
PMID- 29942504
TI - A comparative analysis of survival of patients on dialysis and after kidney
transplantation.
AB - Background: Kidney transplant survival benefits are not observed for around 8
months after transplantation because of a higher complications rate in early post
transplant periods. This study compares survival of patients awaiting
transplantation with survival of transplant recipients and non-listed dialysis
patients in Ireland. Methods: In this retrospective analysis, the relative-risk
(RR) of death was assessed with time-dependent, non-proportional hazards
analysis, with adjustment for age, cause of end-stage kidney disease (ESKD), time
from first treatment for ESKD to placement on the waiting list and year of
initial placement on the list. Results: A total of 3597 patients were included.
Annual death rates per 100 patient-years at risk for all patients on dialysis,
waiting-list patients and transplant recipients were 16.5, 2.4 and 1.2,
respectively. Death rate was highest among diabetics. The relative risk of death
for all patients on dialysis was five times higher than the waiting-list patients
[RR, 4.90; 95% confidence interval (CI), 3.70-6.52; P < 0.001]. Time to survival
equilibration was 1 year. Thereafter, the 5-year mortality risk was estimated to
be 47% lower than that of the patients on the waiting list (RR, 0.53; 95% CI,
0.37-0.77; P = 0.001). Conclusions: Transplant recipients had a higher risk of
death initially, but a better long-term survival. Time to death risk
equilibration was longer compared with other studies. This could be explained by
better survival rates in our waiting-list cohort.
PMID- 29942505
TI - Interventions to improve hemodialysis adequacy: protocols based on real-time
monitoring of dialysate solute clearance.
AB - Background: The monitoring of dialysate ultraviolet (UV) absorbance is a
validated technology to measure hemodialysis adequacy and allows for continuous
and real-time tracking every session as opposed to the typical once-monthly
assessments. Clinical care guidelines are needed to interpret the findings so as
to troubleshoot problematic absorbance patterns and intervene during an
individual treatment as needed. Methods: When paired with highly structured
clinical care protocols that allow autonomous nursing actions, this technology
has the potential to improve treatment outcomes. These devices measure the UV
absorbance of dialysate solutes to calculate and then display the delivered as
well as predicted clearance for that session. Various technical factors can
affect the course of dialysate absorbance, confound the device's readout of
clearance results and thus lead to challenges for the dialysis unit staff to
properly monitor dialysis adequacy. We analyze optimal and problematic patterns
to the device's 'clearance' display (e.g. due to thrombosis of hollow fibers,
inadequate access blood flow or recirculation) and provide specific interventions
to ensure delivery of an adequate dialysis dose. A rigorous algorithm is
presented with representative device monitor display profiles from actual
hemodialysis sessions. Procedural rationale and interventions are described for
each individual scenario. Conclusion: Real-time hemodialysate UV absorbance
patterns can be used for protocol-based intradialytic interventions to optimize
solute clearance.
PMID- 29942506
TI - Attitudes of nephrologists towards assisted home dialysis in Germany.
AB - Background: Assisted home dialysis (AHD) is an option to combine the benefits of
home dialysis therapy with the needs of dialysis patients who are unable to
perform self-treatment at home. While this method is growing in many countries
worldwide, no data so far are reported for Germany. Methods: A survey was
designed to identify the barriers to the implementation of AHD with the focus on
attitudes and beliefs concerning AHD. The survey was sent to all 2060 members of
the Germany Society of Nephrology. Results: The response rate was 14% of
nephrologists (n = 286), representing 24% of all German centres. AHD was regarded
as a highly meaningful option (>90% of all responding nephrologists). Fifty-five
percent of the centres practice AHD (preferred peritoneal dialysis). The number
of treated patients on AHD was small (77% of the centres treat no more than 10
patients). The nephrologists in centres that performed AHD were of older age and
the number of dialysis patients treated in these centres was greater. AHD was
offered in 57% of centres at chronic kidney disease Stage 4. Inadequate
conventional dialysis and patient's request were reasons for choosing AHD.
Barriers for offering AHD were lack of reimbursement, shortage of staff, lack of
expertise and lack of team motivation. Conclusions: In the view of German
nephrologists, AHD is a meaningful method to provide home dialysis care.
Inadequate funding and a lack of qualified staff were identified as severe
barriers to implementation of AHD. To overcome these barriers and to achieve a
higher penetration of AHD, dedicated actions have to be considered. Further
studies are needed to prove the AHD concept with regard to outcome effects and
cost efficacy.
PMID- 29942507
TI - Efficacy and safety of sofosbuvir-based antiviral therapy to treat hepatitis C
virus infection after kidney transplantation.
AB - Background: The objectives of this pilot study were to assess the efficacy and
safety of an interferon-free sofosbuvir and ribavirin combination regimen to
treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients
and to study the impact of sofosbuvir on calcineurin inhibitor (CNI) drug levels.
Methods: A total of 10 kidney transplant recipients with chronic HCV infection
were included in the study. All received sofosbuvir and ribavirin combination
therapy. The virological response to therapy and the adverse effects of the drugs
were studied. The area under the curve (AUC) and pharmacokinetic data of levels
of CNI were compared while the patients were receiving sofosbuvir and ribavirin
drugs and when they were no longer on these drugs. Results: In all, 9 of 10
patients (90%) achieved rapid virological response (RVR) with undetectable HCV
RNA at 4 weeks and the remaining patient achieved undetectable HCV RNA at 8
weeks. A sustained virological response was seen at 3, 6 and 12 months and was
maintained in all 10 patients (100%). The important aspect of the study is the
effect of treatment with the sofosbuvir-ribavirin combination regimen on the CNI
AUC levels, which resulted in a reduction in the CNI AUC. While used as part of
triple-drug immunosuppression, no change in the dose of CNI (tacrolimus and
cyclosporine) was required based on measurement of C0 levels. Conclusions: The
sofosbuvir and ribavirin combination therapy is effective and safe to treat HCV
infection in the post-renal transplant setting. There is a need for close CNI
level monitoring while these patients are on sofosbuvir therapy. With therapy and
viral clearance, there could be reduction in CNI levels due to increased
clearance of CNI drugs, which is shown by the AUC measurements. This could be
important for patients at high risk for rejection.
PMID- 29942508
TI - Feed conversion ratio, residual feed intake and cholecystokinin type A receptor
gene polymorphisms are associated with feed intake and average daily gain in a
Chinese local chicken population.
AB - Background: The feed conversion ratio (FCR) and residual feed intake (RFI) are
common indexes in measuring feed efficiency for livestock. RFI is a feed intake
adjusted for requirements for maintenance and production so these two traits are
related. Similarly, FCR is related to feed intake and weight gain because it is
their ratio. Cholecystokinin type A receptor (CCKAR) plays an important role in
animal digestive process. We examined the interplay of these three parameters in
a local Chinese chicken population. Results: The feed intake (FI) and body
weights (BW) of 1,841 individuals were monitored on a daily basis from 56 to 105
d of age. There was a strong correlation between RFI and average daily feed
intake (ADFI) and a negative correlation between the FCR and daily gain (rg = -
0.710). Furthermore, we identified 51 single nucleotide polymorphisms (SNPs) in
the CCKAR and 4 of these resulted in amino acid mutations. The C334A mutation was
specifically associated with FI and the expected feed intake (EFI) (P < 0.01)
and significantly associated with the average daily gain (ADG) (P < 0.05).
G1290A was significantly associated with FI and EFI (P < 0.05). Conclusion: FCR
is apply to weight selecting, and RFI is more appropriate if the breeding focus
is feed intake. And C334A and G1290A of the CCKAR gene can be deemed as candidate
markers for feed intake and weight gain.
PMID- 29942510
TI - Running on empty - a nationwide large-scale examination of compulsive exercise in
eating disorders.
AB - Background: Compulsive exercise (CE) has been the neglected "Cinderella" among
eating disorder (ED) symptoms, even though it seems to impact severity, treatment
and outcome. This prompted a large-scale and systematic examination of the impact
of CE in a representative ED sample. Methods: CE was examined in over 9000 female
and male patients from a clinical ED database (covering out-patient, day and/or
residential treatment) with respect to prevalence, ED diagnosis, ED symptoms,
clinical features, patient characteristics, and outcome at 1-year follow-up.
Relationships between changes in CE behavior and remission were also examined.
Results: CE was a transdiagnostic symptom, present in nearly half of all patients
(48%). It was associated with greater overall ED pathology, particularly dietary
restraint, and negative perfectionism. Initial CE did not impact remission rate,
but patients continuing or starting CE during treatment had considerably lower
remission rates compared to patients who never engaged in, or ceased with, CE.
Results were comparable for females and males. Conclusions: At baseline, there
were few differences between patients with and without CE, except a somewhat
higher symptom load for patients with CE, and CE did not predict ED outcome.
However, how CE developed during treatment to 1-year follow-up considerably
impacted remission rates. We strongly recommend CE to be systematically assessed,
addressed, and continuously evaluated in all ED patients seeking treatment.
PMID- 29942509
TI - Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast
cancer cells, but does not impact their proliferation and the response to
chemotherapy or radiation.
AB - Background: Ketogenic diets (KDs) or short-term fasting are popular trends
amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB)
is the main physiological ketone body, whose concentration can reach plasma
levels of 2-6 mM during KDs or fasting. The impact of 3-OHB on the biology of
tumor cells described so far is contradictory. Therefore, we investigated the
effect of a physiological concentration of 3 mM 3-OHB on metabolism,
proliferation, and viability of breast cancer (BC) cells in vitro. Methods: Seven
different human BC cell lines (BT20, BT474, HBL100, MCF-7, MDA-MB 231, MDA-MB
468, and T47D) were cultured in medium with 5 mM glucose in the presence of 3 mM
3-OHB at mild hypoxia (5% oxygen) or normoxia (21% oxygen). Metabolic profiling
was performed by quantification of the turnover of glucose, lactate, and 3-OHB
and by Seahorse metabolic flux analysis. Expression of key enzymes of ketolysis
as well as the main monocarboxylic acid transporter MCT2 and the glucose
transporter GLUT1 was analyzed by RT-qPCR and Western blotting. The effect of 3
OHB on short- and long-term cell proliferation as well as chemo- and
radiosensitivity were also analyzed. Results: 3-OHB significantly changed the
oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in BT20
cells resulting in a more oxidative energetic phenotype. MCF-7 and MDA-MB 468
cells had increased ECAR only in response to 3-OHB, while the other three cell
types remained uninfluenced. All cells expressed MCT2 and GLUT1, thus being able
to uptake the metabolites. The consumption of 3-OHB was not strongly linked to
mRNA overexpression of key enzymes of ketolysis and did not correlate with
lactate production and glucose consumption. Neither 3-OHB nor acetoacetate did
interfere with proliferation. Further, 3-OHB incubation did not modify the
response of the tested BC cell lines to chemotherapy or radiation. Conclusions:
We found that a physiological level of 3-OHB can change the energetic profile of
some BC cell lines. However, 3-OHB failed to influence different biologic
processes in these cells, e.g., cell proliferation and the response to common
breast cancer chemotherapy and radiotherapy. Thus, we have no evidence that 3-OHB
generally influences the biology of breast cancer cells in vitro.
PMID- 29942511
TI - Evaluating the use of high-fidelity simulators during mock neonatal resuscitation
scenarios in trying to improve confidence in residents.
AB - Objective: The purpose of this study was to investigate the effect of the use of
high-fidelity simulators with multidisciplinary teaching on self-reported
confidence in residents. Methods: A total of 26 residents participated in a
session led by a pediatric faculty member and a Neonatal Intensive Care Unit
transport nurse using a high-fidelity pediatric simulator. Multiple scenarios
were presented and each resident took turns in various roles. Pre-intervention
surveys based on a 5-point Likert-type scale were given before the scenarios and
were compared to the results of identical post-intervention surveys. Results:
Statistically significant (p < 0.05) pre to post gains for self-confidence were
observed. Improvements in confidence were analyzed using the mean difference. The
largest improvement in confidence was seen in the ability to treat neonatal
respiratory arrest. This was followed by the ability to supervise/run a code, and
the ability to place an umbilical venous catheter. Conclusion: These results
revealed that high-fidelity simulation-based training has significant positive
gains in residents' self-reported confidence.
PMID- 29942512
TI - Increasing variability of body mass and health correlates in Swiss conscripts, a
possible role of relaxed natural selection?
AB - Background and objectives: The body mass index (BMI) is an established
anthropometric index for the development of obesity-related conditions. However,
little is known about the distribution of BMI within a population, especially
about this distribution's temporal change. Here, we analysed changes in the
distribution of height, weight and BMI over the past 140 years based on data of
Swiss conscripts and tested for correlations between anthropometric data and
standard blood parameters. Methods: Height and weight were measured in 59 504
young Swiss males aged 18-19 years during conscription in 1875-79, 1932-36, 1994
and 2010-12. For 65% of conscripts in 2010-12, results of standard blood analysis
were available. We calculated descriptive statistics of the distribution of
height, weight and BMI over the four time periods and tested for associations
between BMI and metabolic parameters. Results: Average and median body height,
body weight and BMI increased over time. Height did no longer increase between
1994 and 2010-12, while weight and BMI still increased over these two decades.
Variability ranges of weight and BMI increased over time, while variation of body
height remained constant. Elevated levels of metabolic and inflammatory blood
parameters were found at both ends of BMI distribution. Conclusions and
implications: Both overweight and underweight subgroups showed similar changes in
inflammation parameters, pointing toward related metabolic deficiencies in both
conditions. In addition to environmental influences, our results indicate a
potential role of relaxed natural selection on genes affecting metabolism and
body composition.
PMID- 29942513
TI - Associations of single nucleotide polymorphisms with mucinous colorectal cancer:
genome-wide common variant and gene-based rare variant analyses.
AB - Background: Colorectal cancer has significant impact on individuals and
healthcare systems. Many genes have been identified to influence its
pathogenesis. However, the genetic basis of mucinous tumor histology, an
aggressive subtype of colorectal cancer, is currently not well-known. This study
aimed to identify common and rare genetic variations that are associated with the
mucinous tumor phenotype. Methods: Genome-wide single nucleotide polymorphism
(SNP) data was investigated in a colorectal cancer patient cohort (n = 505).
Association analyses were performed for 729,373 common SNPs and 275,645 rare
SNPs. Common SNP association analysis was performed using univariable and
multivariable logistic regression under different genetic models. Rare-variant
association analysis was performed using a multi-marker test. Results: No
associations reached the traditional genome-wide significance. However, promising
genetic associations were identified. The identified common SNPs significantly
improved the discriminatory accuracy of the model for mucinous tumor phenotype.
Specifically, the area under the receiver operating characteristic curve
increased from 0.703 (95% CI: 0.634-0.773) to 0.916 (95% CI: 0.873-0.960) when
considering the most significant SNPs. Additionally, the rare variant analysis
identified a number of genetic regions that potentially contain causal rare
variants associated with the mucinous tumor phenotype. Conclusions: This is the
first study applying both common and rare variant analyses to identify genetic
associations with mucinous tumor phenotype using a genome-wide genotype data. Our
results suggested novel associations with mucinous tumors. Once confirmed, these
results will not only help us understand the biological basis of mucinous
histology, but may also help develop targeted treatment options for mucinous
tumors.
PMID- 29942514
TI - microRNA based prognostic biomarkers in pancreatic Cancer.
AB - Despite tremendous research efforts focused on diagnosis and treatment,
pancreatic ductal adenocarcinoma remains the third leading cause of cancer
related death in the United States, with a 5-year overall survival rate of less
than 5%. Although resistance is rather complex, emerging evidence has
demonstrated that epigenetic alterations (e.g. miRNA) have important roles in
PDAC progression as well as resistance to therapy. Certain miRNAs have been
identified as potential prognostic biomarkers in PDAC. In this review, we
summarize the recent developments in miRNA research related to PDAC therapeutic
resistance mechanisms and the potential of miRNAs as prognostic biomarkers for
future clinical management of PDAC.
PMID- 29942516
TI - Sea turtles with "the bends" breathe easy again after oxygen therapy.
PMID- 29942515
TI - An ecophysiologically informed model of seed dispersal by orangutans: linking
animal movement with gut passage across time and space.
AB - Fauna-mediated ecosystem service provision (e.g. seed dispersal) can be difficult
to quantify and predict because it is underpinned by the shifting niches of
multiple interacting organisms. Such interactions are especially complex in
tropical ecosystems, including endangered peat forests of Central Borneo, a
biodiversity hot spot and home to the critically endangered orangutan (Pongo
pygmaeus wurmbii). We combined studies of the digestive physiology of captive
orangutans in Australia with detailed field studies of wild orangutans in the
Natural Laboratory of Peat-Swamp Forest of Sabangau, Central Kalimantan,
Indonesia. By measuring the gut transit time (TT) of indigestible seed mimics
(beads) in captivity and applying this as a temporal constraint to movement data
of wild orangutans, we developed a mechanistic, time-explicit spatial model to
project the seed dispersal patterns by these large-bodied, arboreal frugivores.
We followed seven orangutans and established home range kernels using Time Local
Convex Hull (T-LoCoH) modelling. This allowed us to model individual orangutan
movements and to adjust these models according to gut transit times to estimate
seed dispersal kernels. Female movements were conservative (core ranges of 55 and
52 ha in the wet and dry seasons, respectively) and revisitation rates to the
same location of n = 4 in each 24-h block. Male movements were more
unpredictable, yielding fragmented core ranges and revisitation rates to the same
location of only 1.2 times each 24 h; males also demonstrated large disjunctions
where they moved rapidly over long distances and were frequently lost from view.
Seed dispersal kernels were nested predictably within the core ranges of females,
but not males. We used the T-LoCoH approach to analyse movement ecology, which
offered a powerful tool to predict the primary deposition of seeds by orangutans,
thereby providing a reliable method for making a priori predictions of seed
dispersal dynamics by other frugivores in novel ecosystems.
PMID- 29942518
TI - Validation of a blubber-based endocrine pregnancy test for humpback whales.
AB - Baleen whales have few identifiable external indicators of pregnancy state,
making it challenging to study essential aspects of their biology and population
dynamics. Pregnancy status in other marine mammals has been determined by
measuring progesterone concentrations from a variety of sample matrices, but
logistical constraints have limited such studies in free-swimming baleen whales.
We use an extensive blubber sample archive and associated calving history data to
retrospectively identify samples that correspond to pregnant females and develop
a progesterone-based pregnancy test for humpback whales. The lowest pregnant
blubber progesterone concentration was 54.97 ng g-1, and the mean for the known
pregnant group was 198.74 +/- 180.65 ng g-1. Conversely, females known to be
below the minimum age of sexual maturity (juvenile females) had an overall low
mean progesterone concentration (0.59 +/- 0.25 ng g-1), well below the known
pregnant range. Of the mature females that did not return with a calf (n = 11),
three fell within the known-pregnant range (320.79 +/- 209.34 ng g-1), while the
levels for the remaining eight were two orders of magnitude below the lowest
known-pregnant level (1.63 +/- 1.15 ng g-1). The proportion of females that did
not return with a calf but had values similar to known-pregnant females are
consistent with rates of calf mortality, but other potential explanations were
considered. Our findings support a validated blubber endocrine assignment of
pregnancy corroborated with field life history information, a first for any
baleen whale species. The progesterone values we measured were similar to those
found in different pregnancy states of other cetaceans and support using blubber
biopsy samples for assigning pregnancy in humpback whales. This method can be
applied to existing archives or new samples to better study life history and
population demography broadly across species and populations.
PMID- 29942517
TI - The conservation physiology toolbox: status and opportunities.
AB - For over a century, physiological tools and techniques have been allowing
researchers to characterize how organisms respond to changes in their natural
environment and how they interact with human activities or infrastructure. Over
time, many of these techniques have become part of the conservation physiology
toolbox, which is used to monitor, predict, conserve, and restore plant and
animal populations under threat. Here, we provide a summary of the tools that
currently comprise the conservation physiology toolbox. By assessing patterns in
articles that have been published in 'Conservation Physiology' over the past 5
years that focus on introducing, refining and validating tools, we provide an
overview of where researchers are placing emphasis in terms of taxa and
physiological sub-disciplines. Although there is certainly diversity across the
toolbox, metrics of stress physiology (particularly glucocorticoids) and studies
focusing on mammals have garnered the greatest attention, with both comprising
the majority of publications (>45%). We also summarize the types of validations
that are actively being completed, including those related to logistics (sample
collection, storage and processing), interpretation of variation in physiological
traits and relevance for conservation science. Finally, we provide
recommendations for future tool refinement, with suggestions for: (i) improving
our understanding of the applicability of glucocorticoid physiology; (ii) linking
multiple physiological and non-physiological tools; (iii) establishing a
framework for plant conservation physiology; (iv) assessing links between
environmental disturbance, physiology and fitness; (v) appreciating opportunities
for validations in under-represented taxa; and (vi) emphasizing tool validation
as a core component of research programmes. Overall, we are confident that
conservation physiology will continue to increase its applicability to more taxa,
develop more non-invasive techniques, delineate where limitations exist, and
identify the contexts necessary for interpretation in captivity and the wild.
PMID- 29942519
TI - Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal
of factor Xa inhibitors.
AB - Background: Although factor Xa inhibitors have become a popular choice for
chronic oral anticoagulation, effective drug reversal remains difficult due to a
lack of specific antidote. Currently, 4-factor prothrombin complex concentrate
(4F-PCC) is considered the treatment of choice for factor Xa inhibitor-related
major bleeding. However, safety of 4F-PCC and its risk of thrombosis when used
for this off-label purpose remain unclear. The purpose of this retrospective
study is to determine the rate of thromboembolism when 4F-PCC is used for the
emergent reversal of factor Xa inhibitors. Methods: We conducted a single-center
retrospective review of medical records between 2013 and 2017. Patients were
included if they received 4F-PCC to reverse rivaroxaban, apixaban, or edoxaban
for emergent invasive procedures or during episodes of major bleeding defined as
bleeding with hemodynamic instability, fall in hemoglobin of 2 g/dL, or bleeding
requiring blood transfusion. Thrombotic events including myocardial infarction,
pulmonary embolism, deep vein thrombosis, cerebral vascular accident, and
arterial thrombosis of the limb or mesentery were recorded if they occurred
within 14 days of 4F-PCC administration. Data was analyzed using point and
interval estimation to approximate the rate and confidence interval of
thromboembolic events. Results: Forty-three patients were identified in our
review. Doses of 4F-PCC were determined by the treating physician and mainly
ranged from 25 to 50 IU/kg. Twenty-two patients (51.2%) received both sequential
compression devices (SCDs) and subcutaneous heparin for DVT prophylaxis. Twenty
one patients (48.8%) were placed on SCDs only. Three patients received
concomitant FFP. Thrombotic events within 14 days of 4F-PCC administration
occurred in 1 out of 43 patients (2.1%, 95% CI [0.1-12.3]). This thrombotic event
was an upper extremity DVT which occurred 1 day after the patient received 1325
IU (25 IU/kg) of 4F-PCC to reverse rivaroxaban for traumatic intracranial
hemorrhage. The patient was taken for emergent decompressive craniotomy after
rivaroxaban reversal. In patients who did not undergo surgery or who underwent
minor invasive procedures, no thrombotic events were noted. Conclusion: Based on
our preliminary data, the thromboembolic rate of 4F-PCC when given at a dose of
25-50 IU/kg to emergently reverse rivaroxaban and apixaban appears acceptable.
Since many patients who require 4F-PCC to emergently reverse factor Xa inhibitors
will be at high risk of developing thrombotic events, practitioners should be
highly vigilant of these complications. Large, multicenter prospective trials are
needed to further determine this risk.
PMID- 29942520
TI - Association between serum ferritin and hypertension according to the working type
in Korean men: the fifth Korean National Health and nutrition examination survey
2010-2012.
AB - Background: Several studies suggest that serum ferritin concentrations reflect
systemic inflammation, and high ferritin levels can increase the risk of
hypertension in adult men. Shift work is also known to increase the risk of
hypertension; however, there has been no study about the relationship between
serum ferritin levels and the prevalence of hypertension according to the working
type. Methods: This cross-sectional study included 4,442 male participants (3,651
daytime workers and 791 shift workers) who participated in the fifth Korean
National Health and Nutrition Examination Survey. Hypertension was defined as a
systolic blood pressure greater than or equal to 140 mmHg, a diastolic blood
pressure greater than or equal to 90 mmHg or the current use of antihypertensive
medications regardless of blood pressure values. For the statistical analyses,
serum ferritin levels were reclassified into quartiles, and complex sample
analyses were used to evaluate the relationship between serum ferritin levels and
the prevalence of hypertension according to the working type in this study.
Results: Serum ferritin and shift work were positively associated with the
prevalence of hypertension. The effect of interaction was above multiplicative.
When compared to participants in the lowest serum ferritin quartile, the odds
ratio for hypertension for participants in the highest serum ferritin quartile
was 1.372 (1.027-1.833) in daytime workers and 2.009 (1.042-3.873) in shift
workers after adjustment. Conclusions: The prevalence of hypertension increased
as ferritin levels increased in individuals, especially in shift workers.
PMID- 29942521
TI - Spatial analysis between particulate matter and emergency room visits for
conjunctivitis and keratitis.
AB - Background: The concentration of particulate matter in the air varies depending
on the region because it is lightweight and generated from a variety of sources.
To assess the relationship between particulate matter and eye disease, this study
analyzes the concentration data obtained from spatial analysis of particulate
matter and emergency visit data. Methods: The study included 769 residents of
Daegu, Korea who had visited an emergency room for the problem of conjunctivitis
or keratitis. Concentrations of PM10 and other air pollutants were obtained from
the Korean Ministry of the Environment. PM10 concentrations and the number of
patients from each of 143 administrative dongs (sub-municipal level
administrative units) of the city of Daegu were obtained using spatial analysis.
The patient distribution and PM10 concentration were mapped for comparison, and
their relationship was examined using scatter plot, regression analysis, and the
independent sample t-test. Results: The number of patients with conjunctivitis
and keratitis was significantly higher in the regions of the top 20% areas than
the bottom 20% areas in terms of PM10 concentration. The distribution of PM10
concentration and number of patients was visually similar on the map. The
concentration of PM10 and the number of patients showed a dose-response
relationship. When the concentrations of other air polluta9nts were controlled
for, the numbers of conjunctivitis and keratitis patients were 0.04 per 1000 ER
patients and 0.10 per 1000 ER patients, respectively. Conclusion: As PM10 is
associated with the prevalence of conjunctivitis and keratitis, measures to
reduce particulate matter through environmental methods are needed.
PMID- 29942522
TI - Accuracy of glycosuria, random blood glucose and risk factors as selective
screening tools for gestational diabetes mellitus in comparison with universal
diagnosing.
AB - Objective: Despite the short-term and long-term health implications of
gestational diabetes mellitus (GDM), opinions are divided on selective vis-a-vis
universal screening. We validated the accuracy of screening tests for GDM.
Research design and methods: Pregnant women (n=491) were recruited to this
prospective, blind comparison with a gold standard study. We did selective
screening between 13 and 20 weeks using reagent-strip glycosuria, random
capillary blood glucose (RBG) and the presence of >=1 risk factor(s). Between 20
and 34 weeks, we did universal screening following the 'one-step' approach using
glycated hemoglobin (HbA1c), fasting venous plasma glucose (FPG), and the 1-hour
and the 'gold standard' 2-hour oral glucose tolerance test (OGTT). Tests accuracy
was estimated following the WHO and the National Institute for Health and Care
Excellence (NICE) diagnostic criteria. Overall test performance was determined
from the area under the receiver operating characteristic curve (AUC). Results:
GDM prevalence per 2-hour OGTT was 9.0% for the WHO criteria and 14.3% for the
NICE criteria. Selective screening using glycosuria, RBG and risk factors missed
97.4%, 87.2% and 45.7% of cases, respectively. FPG threshold >=5.1 mmol/L had the
highest clinically relevant sensitivity (68%) and specificity (81%), but FPG
threshold >=5.6 mmol/L had higher positive predictive value. Although sensitivity
of 1-hour OGTT was 39.5%, it had the highest accuracy and diagnostic OR.
Regarding test performance, 1-hour OGTT and FPG were very good (AUC>0.8), RBG was
poor (AUC~0.60), whereas HbA1c was invaluable (AUC<0.5). Conclusions: Selective
screening using glycosuria and random blood glucose is unnecessary due to its low
sensitivity. Fasting glucose >=5.1 mmol/L could be applicable for screening at
the population level. Where 2-hour OGTT is not available, FPG >=5.6 mmol/L,
complemented by the presence of risk factors, could be useful in making
therapeutic decision.
PMID- 29942523
TI - Lower vitamin D levels are associated with higher blood glucose levels in Asian
Indian women with pre-diabetes: a population-based cross-sectional study in North
India.
AB - Background: Asian Indian women are predisposed to develop obesity, metabolic
syndrome and vitamin D deficiency. Relationship of vitamin D deficiency with
blood glucose levels has not been explored in Asian Indian women with pre
diabetes. Objective: We evaluated the associations of serum 25-hydroxy vitamin D
(25(OH)D) concentrations among adult women with the pre-diabetes residing in
North India (Delhi). Methods: This cross-sectional population-based study
involved 797 women with pre-diabetes aged 20-60 years. Blood pressure, body mass
index (BMI), fasting blood glucose (FBG), extent of sun exposure and serum
25(OH)D levels were assessed. For purpose of analysis, serum 25(OH)D levels
(nmol/L) were categorized in quintiles as follows: 0-21.5 (first quintile), 21.51
35.60 (second quintile), 35.61-46.50 (third quintile), 46.51-62.30 (fourth
quintile) and >62.31 (fifth quintile). Result: The prevalence (%) of vitamin D
deficiency, insufficiency and sufficiency was 68.6, 25.9 and 5.5, respectively.
Mean age (p=0.004), systolic (p=0.05) and diastolic (p=0.04) blood pressure,
weight (p=0.03), BMI (p=0.04) and FBG (p=0.02) were significantly higher in
subjects with vitamin D deficiency as compared with those with vitamin D
insufficiency and sufficiency. Unadjusted mean values of FBG were significantly
decreased in fourth (p=0.02) and fifth quintiles (p=0.030) of 25(OH)D levels as
compared with second quintile. Furthermore, after adjusting for age and family
income FBG levels were significantly increased in first quintile (compared with
fourth (p=0.012) and fifth (p=0.018) quintiles) and second quintile (compared
with fourth (p=0.003) and fifth (p=0.004) quintiles) of 25(OH)D levels,
respectively. Conclusion: Lower vitamin D levels are associated with higher blood
glucose values in Asian Indian women with pre-diabetes. These findings need
confirmation in case-control and prospective studies.
PMID- 29942524
TI - Oral diabetes medication monotherapy and short-term mortality in individuals with
type 2 diabetes and coronary artery disease.
AB - Objective: To determine whether sulfonylurea use, compared with non-sulfonylurea
oral diabetes medication use, was associated with 2-year mortality in individuals
with well-controlled diabetes and coronary artery disease (CAD). Research design
and methods: We studied 5352 US veterans with type 2 diabetes, obstructive CAD on
coronary angiography, hemoglobin A1c <=7.5% at the time of catheterization, and
taking zero or one oral diabetes medication (categorized as no medications, non
sulfonylurea medication, or sulfonylurea). We estimated the association between
medication category and 2-year mortality using inverse probability of treatment
weighted (IPW) standardized mortality differences and IPW multivariable Cox
proportional hazards regression. Results: 49%, 35%, and 16% of the participants
were on no diabetes medications, non-sulfonylurea medications, and sulfonylureas,
respectively. In individuals on no medications, non-sulfonylurea medications, and
sulfonylureas, the unadjusted mortality rates were 6.6%, 5.2%, and 11.9%,
respectively, and the IPW-standardized mortality rates were 5.9%, 6.5%, and 9.7%,
respectively. The standardized absolute 2-year mortality difference between non
sulfonylurea and sulfonylurea groups was 3.2% (95% CI 0.7 to 5.7) (p=0.01). In
Cox proportional hazards models, the point estimate suggested that sulfonylurea
use might be associated with greater hazard of mortality than non-sulfonylurea
medication use, but this finding was not statistically significant (HR 1.38 (95%
CI 1.00 to 1.93), p=0.05). We did not observe significant mortality differences
between individuals on no diabetes medications and non-sulfonylurea users.
Conclusions: Sulfonylurea use was common (nearly one-third of those taking
medications) and was associated with increased 2-year mortality in individuals
with obstructive CAD. The significance of the association between sulfonylurea
use and mortality was attenuated in fully adjusted survival models. Caution with
sulfonylurea use may be warranted for patients with well-controlled diabetes and
CAD, and metformin or newer diabetes medications with cardiovascular safety data
could be considered as alternatives when individualizing therapy.
PMID- 29942525
TI - Left ventricular chamber dilation and filling pressure may help to categorise
patients with type 2 diabetes.
AB - Background: Type 2 diabetes may alter cardiac structure and function. Many
patients with type 2 diabetes have diastolic dysfunction with preserved ejection
fraction (EF). Recently, this latter measure was criticised. Thus, this research
looked at the impact of left ventricular end-diastolic volume and E/e' ratio
variations in patients with type 2 diabetes and preserved EF with the aim to
recognise different clinical phenotypes. Methods: In this cross-sectional study,
we evaluated 176 men affected by type 2 diabetes with transthoracic
echocardiography. All subjects have preserved EF (>50%). Patients were stratified
into four groups based on the median value of both left ventricular end-diastolic
volume and E/e' ratio, and the clinical variables were registered. The
independent predictors associated with the groups were analysed by a multinomial
logistic regression model. Results: Diabetes duration, age, estimated glomerular
filtration rate and antihypertensive treatments were significantly different
among the groups as were EF, left atrial volume index (LAVI), E/A, septum
thickness and s' mean wave. Multinomial regression analysis showed that the
groups significantly differed for age, diabetes duration, EF, LAVI, septum
thickness and s' mean wave. The main result of this study was that patients with
higher left ventricular volume and higher E/e' ratio (group 2) showed the worse
clinical profile. Conclusions: Our study might suggest that variations of left
ventricular end-diastolic volume along with E/e' ratio variations, even in the
normal range, may allow to recognise phenotypes of patients with type 2 diabetes
with worse clinical characteristics. This finding should be tested in prospective
studies to assess the predictive roles of these phenotypes.
PMID- 29942527
TI - Elevation of maternal serum sFlt-1 in pregnancy with mirror syndrome caused by
fetal cardiac failure.
AB - Mirror syndrome (MS) is characterized by the combination of maternal generalized
edema, fetal hydrops and placental hypertrophy. A shift of the serum placenta
derived angiogenic factor like sFlt-1 in MS is similar to that in pre-eclampsia
(PE). We experienced a MS case caused by cardiac myopathy in the fetus with
normal cardiac structure. A 27-year-old primiparous woman at 28 weeks of
gestation had systemic edema without hypertension and proteinuria. Her symptoms
rapidly disappeared after delivery. Compared with previously reported MS cases
with maternal hypertension or proteinuria, the serum sFlt-1 level was lower in
our case. Severity of maternal symptoms in MS might be paralleled with the serum
sFlt-1 level. Additionally, serum hCG level in MS is much higher than that in PE.
Maternal edema rather than hypertension and proteinuria can be more remarkable in
MS compared with PE. It can be potentially explained by increased serum hCG
level.
PMID- 29942526
TI - Physicians' real-world experience with IDegLira: results of a European survey.
AB - Objective: This study aimed to build on the current clinical findings and
investigate physicians' experiences and level of satisfaction in using insulin
degludec/liraglutide (IDegLira) to treat patients with type 2 diabetes (T2D).
Research design and methods: This multicountry, European online survey included
respondents from primary (n=132) and secondary (n=103) care and examined
physicians' use, confidence and satisfaction with IDegLira. To standardize
responses, 24 of 28 questions pertained to an 'average patient' with T2D who has
no major comorbidities, aged 35-70 years, with average cognitive ability/normal
mental status and body mass index >=25 kg/m2. Results: The majority (70%) of
respondents prescribe IDegLira in the same visit they first mention it, with
uncontrolled glycated hemoglobin (HbA1c) (44%) and weight gain (22%) being the
most common reasons. On average, physicians reported that patients weighed 95 kg
and the HbA1c level was 9.0% at initiation. Physicians also reported the average
HbA1c target set was 7.1%; 76% of patients achieved their target. On average,
patients achieved their HbA1c target in <6 months, and the average dose of
IDegLira in patients in glycemic control was 28 dose steps. Respondents were more
satisfied with IDegLira than basal-bolus therapy across all parameters assessed,
including reaching HbA1c targets (59%), number of injections (77%) and avoiding
weight gain (84%). Correspondingly, 77% of physicians reported that IDegLira had
more potential to improve patient motivation compared with basal-bolus to reach
target blood glucose levels. Conclusions: Real-world experience of IDegLira is
consistent with previous trials/studies, with no major differences between
primary and secondary care. Importantly, the majority of respondents were
more/much more satisfied with IDegLira than with basal-bolus therapy.
PMID- 29942528
TI - Acute parotitis due to MRSA causing Lemierre's syndrome.
AB - We report a case of septic thrombophlebitis of the right internal jugular vein
linked with right-sided acute parotitis caused by methicillin-resistant
Staphylococcus aureus (MRSA) in a patient who had recently undergone a pylorus
preserving pancreaticoduodenectomy. Our case is unique because acute parotitis is
a less-recognized cause of Lemierre's syndrome, never previously linked with MRSA
infection in this context. We review the literature on diagnosis and management
of Lemierre's syndrome caused by acute parotitis. Prompt diagnosis and aggressive
antibiotics ensured a favourable outcome.
PMID- 29942529
TI - Holo-cranial metastasis to the brain from breast cancer.
PMID- 29942530
TI - Holo-cord drop metastasis from a glioblastoma-when rarity meets reality.
PMID- 29942531
TI - Unilateral leg oedema due to spontaneous Achilles tendon rupture.
AB - This is a case of severe unilateral lower leg oedema in a 77-year-old man, due to
a spontaneous, complete Achilles tendon rupture. What makes this case unusual is
the absence of trauma in the patient's history. The correct diagnosis was made
only after magnetic resonance imaging. However, a thorough clinical re
examination of the patient revealed an inability to stand and walk on toes and a
palpable defect of the Achilles tendon, which was difficult to detect due to the
marked oedema. This case reminds physicians that an Achilles tendon rupture can
also occur without clear history of trauma and should be considered as a cause of
unilateral lower leg oedema, especially in presence of pain. Moreover, it
illustrates the crucial role of a thorough clinical examination (including
standing and walking on toes) for the correct diagnosis, even when restricting
factors such as oedema and pain are present.
PMID- 29942532
TI - Single dose of propofol causing propofol infusion syndrome in a newborn.
AB - Propofol infusion syndrome (PRIS) is a rare syndrome originally described in
critically ill children undergoing long-term (> 48 h) propofol infusion at high
doses (> 4 mg/kg/h). Severe metabolic acidosis, rhabdomyolysis, renal failure and
fatal cardiac failure are the features. Herein, we present a case of a newborn
who developed PRIS after a single bolus dose of propofol at 3.2 mg/kg/do,
developing rhabdomyolysis and severe metabolic acidosis, with a successful
outcome after medical therapy.
PMID- 29942534
TI - Erratum.
AB - [This corrects the article DOI: 10.1177/2054270417751866.].
PMID- 29942533
TI - Participation of the caudal cerebellar lobule IX to the dorsal attentional
network.
AB - Background: We seeked for specific cerebellar contribution within the dorsal
attentional network (DAN), using Independent Component Analysis (ICA). Methods:
ICA-based analysis was performed on brain resting-state functional images of 19
volunteers. Results: We confirmed that DAN includes bilaterally: lobules VI-VII
(crus I) and VIIB-VIIIA, as previously reported by Region-Of-Interest (ROI)-based
functional connectivity studies. We also found that lobule IX (tonsillae), and as
well as the superior and, likely, inferior colliculi. Also belong to DAN. The
part of lobule IX in relation to DAN is located more caudally and laterally, and
less extensive than the more rostral part of this lobule belonging to the default
mode network (DMN). Conclusion: Rostral and caudal tonsillae partake in the DMN
and DAN, respectively. The latter could subserve either eye movement control in
relation to the oculomotor parieto-frontal network, partially congruent with the
DAN, or more cognitive functions due to functional reallocation within the DAN.
PMID- 29942535
TI - IgA nephropathy in African Americans: uncommon but possible.
AB - Though IgA nephropathy is relatively uncommon in African Americans, our case
serves as a reminder that it needs to be considered in the differentials when
these patients present with proliferative glomerulonephritis.
PMID- 29942537
TI - Welcome to the Digital Health revolution.
PMID- 29942536
TI - Epidemiology of multidrug-resistant tuberculosis (MDR-TB) in Ethiopia: a
systematic review and meta-analysis of the prevalence, determinants and treatment
outcome.
AB - Introduction: The emergence of MDR-TB remained a major public health threat
particularly in developing countries. With increased prevalence and complexity of
treatment, the burden of MDR-TB challenged the country. It is of an important;
the epidemiology of drug resistant TB is not well understood. There are few
studies conducted to assess the prevalence, determinants and treatment outcome of
MDR-TB with inconclusive finding. Therefore, we aimed to conduct a systematic
review and meta-analysis on Epidemiology of MDR-TB in Ethiopia, So that policy
makers and other stalk holders could have pooled evidence on the problem to make
a decision. Methods: The review was conducted through a systematic literature
search of articles published between 1997 and 2017. Five bibliographic databases
and libraries: PubMed/Medline, Global Health Database, Embase, the Cochrane
Library, and African Index Medicus were used. After cleaning and sorting,
analysis was performed using STATA version 11. The pooled rate of MDR-TB
prevalence, determinants and treatment outcome was estimated with a random
effects model. Heterogeneity was assessed by the I2 and publication bias through
funnel plot. Results: The 34 studies that were retained for final analysis
enrolled a total of 7461 TB or MDR-TB patients. We found that 2.18% (95% CI 1.44
2.92%) of newly diagnosed and 21.07% (95% CI 11.47-30.67%) of previously treated
patients have MDR-TB with overall prevalence of 7.24% (95% CI 6.11-8.37). History
of previous treatment is the major determinant (pooled OR = 4.78 (95% CI 3.16
6.39)), while contact history and adherence also contributed. In this review the
pooled death computed among 5 articles showed that 12.25% (95% CI 9.39-15.11%) of
MDR-TB patients were died in the course of treatment. Complication, drug side
effects and HIV infection were the main determinants for the death. Conclusion
and recommendation: The prevalence is by far higher than the previous reports. It
is mainly associated with history of previous treatment along with contact
history. However, the treatment outcomes are comparable with previous studies,
yet it is a concern. Comorbidities, drug side effects and HIV sero-positivity
were the determinants. Thus, proper treatment of drug susceptible TB and early
detection and treatment of MDR-TB before complication develops along with
prevention of drug side effect and contacts with MDR-TB cases are very important.
PMID- 29942538
TI - Managing stress through the Stress Free app: Practices of self-care in digitally
mediated spaces.
AB - In this paper we are concerned with the question of how we feel when living in
concert with multiple technologies. More specifically, we are focused on the
influx of digital apps designed to manage psychological wellbeing. We draw on
empirical work exploring one such app, Stress Free, and focus on the experiences
of stress and technological tools designed to lessen stress. Our concern is with
the way that technologies become part of the experience of stress as opposed to
solely understanding the app as a tool aimed to reduce the occurrence and
severity of stress. This involves taking a theoretical journey through
philosophies of technology that provide valuable resources for conceptualising
the relational characteristics of digitally mediated stress. Our wider interest
is to speak to broader concerns with the movement to 'digital care' and the
implications for how we conceptualise technology, self and care therein.
PMID- 29942539
TI - Addressing barriers to physical activity among women: A feasibility study using
social networking-enabled technology.
AB - Objective: Automated physical activity (PA) monitoring technology and associated
social networks have potential to address barriers to PA, but have rarely been
tested for PA promotion. This technology may be especially beneficial for women,
who experience particular barriers to health-based social networking. The present
study tested the feasibility and acceptability of pairing women as PA partners
via technology-connected social networking. Social comparison (i.e. tendency to
make self-evaluations relative to others) was examined as a mechanism of
interest. Method: Overweight women (n = 12, Mage = 46, MBMI = 32.60 kg/m2) used a
PA sensor (daily wear = 93%) and communicated with an assigned partner
(introduced via technology-connected social networking) for four weeks. Partners
did not know one another prior to study enrollment. Results: PA meaningfully
increased during the program, and was highest among participants who endorsed
stronger (vs. weaker) tendencies toward social comparisons (r = 0.64).
Participants identified several benefits of partner communication; however, some
partners had difficulty initiating communication, and direct comparisons with
partners were seen as unhelpful in this context. Most participants found the PA
sensor beneficial, showed high compliance with daily wear recommendations, and
reported an intent to continue using the PA sensor. Participants endorsed
satisfaction with the program's approach and confidence in maintaining PA gains.
Conclusions: These findings support the use of automated PA sensors and
facilitated partner communication via social networking to promote PA among
women. Insights from participant feedback identify specific avenues for program
improvement; specifically, with respect to the potential difficulties of negative
social comparisons.
PMID- 29942540
TI - Social media used as a health intervention in adolescent health: A systematic
review of the literature.
AB - Objective: Adolescents are known to be high users of social media, and social
media is beginning to be used in health care. The primary objective of this
review was to determine the current state of play on the use of social media as a
health intervention in addressing the health of adolescents. Methods: Six
databases were searched: CINAHL, Medline, Scopus, ProQuest, Psych Info and
Science Direct, from 2000-2013. The review process followed PRISMA guidelines
with quality assessments of the selected articles undertaken. Results: Three
studies used social media as a health intervention in adolescent health. Facebook
was the social media of choice. The way this social media tool was incorporated
as the intervention varied. None of the social media interventions had a
significant or sustained impact on the primary outcomes of the studies reviewed.
Measures of social media process were limited and lacked meaning. Conclusions:
The selected papers provided insight into the beginning phase of using social
media as a health intervention to address adolescent health. The review
highlights three important areas for consideration when undertaking research on
the use of social media as a health intervention for adolescents: the newness of
using social media as a health intervention, the importance of the use of
rigorous methodological processes when using social media as a health
intervention, and the need to develop further knowledge on adolescents' use of
social media, in particular their hidden world of social media.
PMID- 29942541
TI - UK policy on social networking sites and online health: From informed patient to
informed consumer?
AB - Background: Social networking sites offer new opportunities for communication
between and amongst health care professionals, patients and members of the
public. In doing so, they have the potential to facilitate public access to
health care information, peer-support networks, health policy fora and online
consultations. Government policies and guidance from professional organisations
have begun to address the potential of these technologies in the domain of health
care and the responsibilities they entail for their users. Objective: Adapting a
discourse analytic framework for the analysis of policy documents, this review
paper critically examines discussions of social networking sites in recent
government and professional policy documents. It focuses particularly on who
these organisations claim should use social media, for what purposes, and what
the anticipated outcomes of use will be for patients and the organisations
themselves. Conclusion: Recent policy documents have configured social media as a
new means with which to harvest patient feedback on health care encounters and
communicate health care service information with which patients and the general
public can be 'empowered' to make responsible decisions. In orienting to social
media as a vehicle for enabling consumer choice, these policies encourage the
marketization of health information through a greater role for non-profit and
commercial organisations in the eHealth domain. At the same time, current policy
largely overlooks the role of social media in mediating ongoing support and self
management for patients with long-term conditions.
PMID- 29942542
TI - Virtual research visits and direct-to-consumer genetic testing in Parkinson's
disease.
AB - Objective: The purpose of this study was to conduct a proof-of-concept study to
evaluate remote recruitment and assessment of individuals ("virtual research
visits") with Parkinson's disease who have pursued direct-to-consumer genetic
testing. Methods: Participants in 23andMe's "Parkinson's Research Community" were
contacted by 23andMe. Fifty willing participants living in 23 states underwent a
remote, standardized assessment including cognitive and motor tests by a
neurologist via video conferencing and then completed a survey. Primary outcomes
assessed were (a) proportion of participants who completed the remote
assessments; (b) level of agreement (using Cohen's kappa coefficient) of patient
reported data with that of a neurologist; and (c) interest in future virtual
research visits. Results: The self-reported diagnosis of Parkinson's disease was
confirmed in all cases (k = 1.00). The level of agreement for age of symptom
onset (k = 0.97) and family history (k = 0.85) was very good but worse for
falling (k = 0.59), tremor (k = 0.56), light-headedness (k = 0.31), and urine
control (k = 0.15). Thirty-eight (76%) of the 50 participants completed a post
assessment survey, and 87% of respondents said they would be more or much more
willing to participate in future clinical trials if they could do research visits
remotely. Conclusion: Remote clinical assessments of individuals with known
genotypes were conducted nationally and rapidly from a single site, confirmed
self-reported diagnosis, and were received favorably. Direct-to-consumer genetic
testing and virtual research visits together may enable characterization of
genotype and phenotype for geographically diverse populations.
PMID- 29942543
TI - Improving health outcomes for young people with long term conditions: The role of
digital communication in current and future patient-clinician communication for
NHS providers of specialist clinical services for young people - LYNC study
protocol.
AB - Background: Young people living with long term conditions are vulnerable to
health service disengagement. This endangers their long term health. Studies
report requests for digital forms of communication - email, text, social media -
with their health care team. Digital clinical communication is troublesome for
the UK NHS. Aim: In this article we aim to present the research protocol for
evaluating the impacts and outcomes of digital clinical communications for young
people living with long term conditions and provide critical analysis of their
use, monitoring and evaluation by NHS providers (LYNC study: Long term
conditions, Young people, Networked Communications). Methods: The research
involves: (a) patient and public involvement activities with 16-24 year olds with
and without long term health conditions; (b) six literature reviews; (c) case
studies - the main empirical part of the study - and (d) synthesis and a
consensus meeting. Case studies use a mixed methods design. Interviews and non
participant observation of practitioners and patients communicating in up to 20
specialist clinical settings will be combined with data, aggregated at the case
level (non-identifiable patient data) on a range of clinical outcomes meaningful
within the case and across cases. We will describe the use of digital clinical
communication from the perspective of patients, clinical staff, support staff and
managers, interviewing up to 15 young people and 15 staff per case study. Outcome
data includes emergency admissions, A&E attendance and DNA (did not attend)
rates. Case studies will be analysed to understand impacts of digital clinical
communication on patient health outcomes, health care costs and consumption,
ethics and patient safety.
PMID- 29942544
TI - Theory-based strategies for enhancing the impact and usage of digital health
behaviour change interventions: A review.
AB - There is growing evidence that digital interventions can successfully effect
meaningful changes in health-related behaviour. However, optimisation of digital
intervention delivery is challenged by low usage, high attrition and small effect
sizes. Whilst a number of conceptual frameworks and models exist to guide
intervention planning and development, insufficient attention has been paid to
how existing psychological theory could inform the optimal implementation and
delivery of the design features commonly used in digital health behaviour change
interventions. This paper provides a critical review of psychological theories
and models in order to consider their implications for the design of digital
interventions. The theories reviewed include theories of: persuasion and attitude
change; motivation; volition and self-regulation; patient preferences for
participation in medical decision making; and social support. A set of theory
based guidelines is provided to inform the development of future interventions.
PMID- 29942545
TI - Towards 'Engagement 2.0': Insights from a study of dynamic consent with biobank
participants.
AB - Web 2.0 technologies have enabled new methods of engagement, moving from static
mono-directional sources of information to interactive user-led experiences. Use
of Web 2.0 technologies for engagement is gaining momentum within the health
sector however this is still in its infancy in biobanking research. This paper
reports on findings from focus groups with biobank participants to gauge their
views on a Web 2.0 dynamic consent interface. The findings from this study
suggest that participants would welcome more interactive engagement with
biobanks, and the opportunity to hear more about how their data and samples are
being used in research. We propose that by adopting Web 2.0 tools for dynamic
consent, we can move towards an 'Engagement 2.0' model whereby research
participants have the opportunity for more interactive engagement with medical
research, setting up a two-way communication channel between participants and
researchers, for the benefit of both.
PMID- 29942546
TI - Creating a database of internet-based clinical trials to support a public-led
research programme: A descriptive analysis.
AB - Background: Online trials are rapidly growing in number, offering potential
benefits but also methodological, ethical and social challenges. The
International Network for Knowledge on Well-being (ThinkWellTM) aims to increase
public and patient participation in the prioritisation, design and conduct of
research through the use of technologies. Objective: We aim to provide a baseline
understanding of the online trial environment, determining how many trials have
used internet-based technologies; how they have been used; and how use has
developed over time. Methods: We searched a range of bibliographic databases to
March 2015, with no date limits, supplemented by citation searching and
references provided by experts in the field. Results were screened against
inclusion and exclusion criteria, and included studies mapped against a number of
key dimensions, with key themes developed iteratively throughout the process.
Results: We identified 1992 internet-based trials to March 2015. The number of
reported studies increased substantially over the study timeframe. The largest
number of trials were conducted in the USA (49.7%), followed by The Netherlands
(10.2%); Australia (8.5%); the United Kingdom (5.8%); Sweden (4.6%); Canada (4%);
and Germany (2.6%). South Korea (1.5%) has the highest number of reported trials
for other continents. There is a predominance of interventions addressing core
public health challenges including obesity (8.6%), smoking cessation (5.9%),
alcohol abuse (7.7%) and physical activity (10.2%); in mental health issues such
as depression (10.9%) and anxiety (5.6%); and conditions where self-management
(16.6%) or monitoring (8.1%) is a major feature of care. Conclusions: The results
confirm an increase in the use of the internet in trials. Key themes have emerged
from the analysis and further research will be undertaken in order to investigate
how the data can be used to improve trial design and recruitment, and to build an
open access resource to support the public-led research agenda.
PMID- 29942547
TI - Harnessing patient feedback data: A challenge for policy and service improvement.
PMID- 29942548
TI - #ec: Findings and implications from a quantitative content analysis of tweets
about emergency contraception.
AB - Twitter, a popular social media, helps users around the world quickly share and
receive information. The way in which Twitter frames health issues - especially
controversial issues like emergency contraception (EC) - can influence public
opinion. The current study analyzed all English-language EC-related tweets from
March 2011 (n = 3535). Variables measured user characteristics (e.g. gender),
content (e.g. news, humor), Twitter-specific strategy (e.g. retweet), and certain
time periods (e.g. weekends). The analysis applied chi-square and regression
analyses to the variables. Tweets most frequently focused on content related to
news (27.27%), accessing EC (27.27%), and humor (25.63%). Among tweets that were
shared, however, the most common content included humor, followed by
personal/vicarious experience. Although only 5.54% of shared tweets mentioned
promiscuity, this content category had the strongest odds for being shared (OR =
1.51; p = 0.031). The tweet content with lowest odds of being shared were side
effects (OR = 0.24; p < 0.001), drug safety (OR = 0.44; p < 0.001), and news (OR
= 0.44; p < 0.001). Tweets with the greatest odds of having been sent on a
weekend sought advice (OR = 1.94; p = 0.012), addressed personal or vicarious
experience (OR = 1.91; p < 0.001), or contained humor (OR = 1.56; p < 0.001).
Similar patterns occurred in tweets sent around St. Patrick's Day. Only a few
differences were found in the ways in which male and female individuals discussed
EC on Twitter. In particular, when compared to males, females mentioned birth
control (p = 0.002), EC side effects (p = 0.024), and issues related to
responsibility (p = 0.003) more often than expected. Study findings offer timely
and practical suggestions for public health professionals wanting to communicate
about EC via Twitter.
PMID- 29942550
TI - The perceived impact of suicide-related internet use: A survey of young
Australians who have gone online for suicide-related reasons.
AB - The aim of the present study was to examine the perceived impact of suicide
related Internet use, particularly of websites with potentially harmful attitudes
towards suicide (encouraging suicide or discouraging help-seeking) or potentially
helpful attitudes towards suicide (discouraging suicide or encouraging help
seeking), the online availability of suicide methods and online suicide
communities The present study used a cross-sectional, anonymous online survey.
Participants were 102 Australian citizens and permanent residents recruited from
various, non-mental health-related websites, aged 18-24 years, who had gone
online for suicide-related reasons within the past 12 months. Overall, there was
a significant decrease in participants' retrospective ratings of their suicidal
thoughts and behaviours from before they first went online for suicide-related
reasons to the time of the survey. However, characteristics of websites did not
significantly predict users' suicidal thoughts and behaviours. Participants
reported both positive and negative online experiences, even for similar forms of
suicide-related Internet use (e.g. reading information on suicide methods). The
findings suggest that suicide-related Internet use is complex and its impact
cannot necessarily be strictly attributed to specific types of websites or online
content. The Internet may pose a risk to some vulnerable individuals but may also
provide helpful, valuable support to others. Mental health professionals should
therefore be aware of these potential risks and direct more efforts towards
online suicide prevention.
PMID- 29942549
TI - A social network analysis of supportive interactions on prenatal sites.
AB - Objective: The purpose of this exploratory study was to validate and extend
previous research on social support by identifying which dimensions of social
support are most commonly exchanged on health-related social networking sites and
how social network structure varies with each support dimension exchanged.
Methods: This research applies a multiple case study approach by examining two
social networking sites that focus on pregnancy and prenatal health. For one
month, support seeking and providing messages were content analyzed and a social
network analysis examined the connections between members. Results: The sample
size consisted of 525 support-seeking messages and 1965 support-providing
messages. Findings indicate that participants requested informational and
emotional support more than esteem and network support, with no requests for
tangible support. Findings also suggest participants substituted emotional
support for informational support when they were unable to provide the
information sought. The social network analysis showed that network structure
varied across support dimensions, with the informational and emotional support
networks having the largest number of members and greatest density and
reciprocity. Conclusions: This study suggests that online support networks are
fairly effective in meeting participants' needs. The support dimension sought was
generally provided and when it was not another dimension of support may have been
substituted; thus, participants may have benefitted in unintended ways. The data
also suggest there may be an optimal network size to support member engagement,
whereby too large of a network may facilitate diffusion of responsibility and too
small a network may not facilitate enough momentum to support a well-connected
community.
PMID- 29942551
TI - Virtual rehabilitation: What are the practical barriers for home-based research?
AB - Virtual reality technologies are becoming increasingly accessible and affordable
to deliver, and consequently the interest in applying virtual reality within
rehabilitation is growing. This has resulted in the emergence of research
exploring the utility of virtual reality and interactive video gaming
interventions for home use by patients. The aim of this paper is to highlight the
practical factors and difficulties that may be encountered in research in this
area, and to make recommendations for addressing these. Whilst this paper focuses
on examples drawn mainly from stroke rehabilitation research, many of the issues
raised are relevant to other conditions where virtual reality approaches have the
potential to be applied to home-based rehabilitation.
PMID- 29942552
TI - Semantic networks of interests in online non-suicidal self-injury communities.
AB - People who engage in non-suicidal self-injury (NSSI) often conceal their
practices, which limits examination and understanding of their engagement. The
goal of this research is to utilize data from public online social networks
(namely, LiveJournal, a major blogging social networking site) to observe the
NSSI population in a naturally occurring setting. Specifically, the focus of this
paper is the interests publicly declared by LiveJournal users. In the course of
study, we collected the self-declared interests of 25,000 users who are members
of or participate in 139 NSSI-related communities. We constructed a family of
semantic networks of interests based on their similarity. The semantic networks
are structured and contain several dense clusters-semantic domains-that include
NSSI-specific interests (such as self-injury and razor), references to music
performers (such as evanescence), and general daily life and creativity related
interests (such as poetry and friendship). Assuming users are genuine in their
declarations, the clusters reveal distinct patterns of interest and may signal
keys to NSSI.
PMID- 29942554
TI - An investigation of strategies used in alcohol brand marketing and alcohol
related health promotion on Facebook.
AB - Objective: Alcohol brands are incorporating social networking sites (SNS) into
their marketing programmes. SNS are also being used to reduce alcohol consumption
and harms by health promotion organisations. Marketing via SNS can attempt to
influence consumers using a range of strategies from traditional marketing,
social media, and behaviour change theory. This study systematically quantifies
marketing strategies used by alcohol brands and health promoters on Facebook.
Methods: We identified the 10 most popular alcohol brands and health promotion
organisations in Australia on Facebook and extracted all posts from April 2014. A
framework was developed, listing 33 SNS marketing strategies. The frequency of
use of each strategy in posts was counted for all profiles. Results: The median
number of fans of alcohol brands was 189,290 compared with 7562 for health
promotion pages. A total of 210 Facebook posts were analysed. Popular marketing
strategies included visual attraction, connecting with other organisations, and
links to culture and events. Time-specific and day-specific posts and tweets were
used more regularly by alcohol brands than health promotion agencies.
Conclusions: Alcohol brands remain substantially more popular than health
promotion organisations, and this difference is likely driven by offline factors
rather than specific use of marketing strategies. However, health promotion
organisations can learn from the strategies used by popular brands, particularly
in the use of time and day-specific content.
PMID- 29942553
TI - Feasibility of conducting a web-based survey of patient-reported outcomes and
rehabilitation progress.
AB - Background: Web-based surveys provide an efficient means to track clinical
outcomes over time without the use of clinician time for additional paperwork.
Our purpose was to determine the feasibility of utilizing web-based surveys to
capture rehabilitation compliance and clinical outcomes among postoperative
orthopedic patients. The study hypotheses were that (a) recruitment rate would be
high (>90%), (b) patients receiving surveys every two weeks would demonstrate
higher response rates than patients that receive surveys every four weeks, and
(c) response rates would decrease over time. Methods: The study deaign involved a
longitudinal cohort. Surgical knee patients were recruited for study
participation during their first post-operative visit (n = 59, 34.9 +/- 12.0
years of age). Patients with Internet access, an available email address and
willingness to participate were counter-balanced into groups to receive surveys
either every two or four weeks for 24 weeks post-surgery. The surveys included
questions related to rehabilitation and questions from standard patient-reported
outcome measures. Outcome measures included recruitment rate (participants
consented/patients approached), eligibility (participants with email/participants
consented), willingness (willing participants/participants eligible), and
response rate (percentage of surveys completed by willing participants). Results:
Fifty-nine patients were approached regarding participation. Recruitment rate was
98% (n = 58). Eligibility was 95% (n = 55), and willingness was 91% (n = 50). The
average response rate was 42% across both groups. There was no difference in the
median response rates between the two-week (50%, range 0-100%) and four-week
groups (33%, range 0-100%; p = 0.55). Conclusions: Although patients report being
willing and able to participate in a web-based survey, response rates failed to
exceed 50% in both the two-week and four-week groups. Furthermore, response rates
began to decrease after the first three months postoperatively. Therefore,
supplementary data collection procedures may be necessary to meet established
research quality standards.
PMID- 29942555
TI - Accuracy of the Yamax CW-701 Pedometer for measuring steps in controlled and free
living conditions.
AB - Objective: The Yamax Digi-Walker CW-701 (Yamax CW-701) is a low-cost pedometer
that includes a 7-day memory, a 2-week cumulative memory, and automatically
resets to zero at midnight. To date, the accuracy of the Yamax CW-701 has not
been determined. The purpose of this study was to assess the accuracy of steps
recorded by the Yamax CW-701 pedometer compared with actual steps and two other
devices. Methods: The study was conducted in a campus-based lab and in free
living settings with 22 students, faculty, and staff at a mid-sized university in
the Southeastern US. While wearing a Yamax CW-701, Yamax Digi-Walker SW-200, and
an ActiGraph GTX3 accelerometer, participants engaged in activities at variable
speeds and conditions. To assess accuracy of each device, steps recorded were
compared with actual step counts. Statistical tests included paired sample t
tests, percent accuracy, intraclass correlation coefficient, and Bland-Altman
plots. Results: The Yamax CW-701 demonstrated reliability and concurrent validity
during walking at a fast pace and walking on a track, and in free-living
conditions. Decreased accuracy was noted walking at a slow pace. Conclusions:
These findings are consistent with prior research. With most pedometers and
accelerometers, adequate force and intensity must be present for a step to
register. The Yamax CW-701 is accurate in recording steps taken while walking at
a fast pace and in free-living settings.
PMID- 29942556
TI - Validity of the Samsung Phone S Health application for assessing steps and energy
expenditure during walking and running: Does phone placement matter?
AB - Background: The emergence of mHealth and the utilization of smartphones in
physical activity interventions warrant a closer examination of validity evidence
for such technology. This study examined the validity of the Samsung S Health
application in measuring steps and energy expenditure. Methods: Twenty-nine
participants (mean age 21.69 +/- 1.63) participated in the study. Participants
carried a Samsung smartphone in their non-dominant hand and right pocket while
walking around a 200-meter track and running on a treadmill at 2.24 m?s-1. Steps
and energy expenditure from the S Health app were compared with StepWatch 3 Step
Activity Monitor steps and indirect calorimetry. Results: No significant
differences between S Health estimated steps and energy expenditure during
walking and their respective criterion measures, regardless of placement. There
was also no significant difference between S Health estimated steps and the
criterion measure during treadmill running, regardless of placement. There was
significant differences between S Health estimated energy expenditure and the
criterion during treadmill running for both placements (both p < 0.001).
Conclusions: The S Health application measures steps and energy expenditure
accurately during self-selected pace walking regardless of placement. Placement
of the phone impacts the S Health application accuracy in measuring physical
activity variables during treadmill running.
PMID- 29942557
TI - Making connections and promoting the profession: Social media use by World
Federation of Occupational Therapists member organisations.
AB - Background: World Federation of Occupational Therapists (WFOT) member
organisations comprise 77 national occupational therapy organisations across the
world. Each national organisation interacts with its members and the public using
diverse methods. Increasingly, national organisations are broadening their
communication methods. Objective: The objective of this study was to examine if
and how occupational therapy organisations are using social media for
communication, and if so, the types of concerns or barriers they experience and
what role they anticipate social media might play in the near future. Methods: An
online survey was developed; 57 of 77 WFOT member organisations responded.
Findings: This study identified that WFOT national organisations are using social
media, to varying degrees, with or without an individual formally assigned to
manage social media. Respondents reported that they used social media to:
communicate with members, promote the organisation and promote the profession.
Commonly expressed needs included assistance with guidelines for ethical social
media use, developing technical expertise, and recognition of limits of time and
competing priorities. Recommendations arising from this research are at the
global, national, local and individual levels and incorporate active
dissemination and pure diffusion approaches. Taking steps to increase the use of
social media could indirectly impact occupational therapy practice through
enhancing organisations' abilities to support practitioners to enhance their
practice. Limitations and recommendations for further research: Although 57% of
WFOT member organisations returned usable responses, there may be some additional
perspectives that were not captured. It would be helpful to contact non
responding organisations to explore their social media use and plans. Further
research could examine how future initiatives put in place by WFOT impact social
media use by member organisations.
PMID- 29942558
TI - Internet use for mental health information and support among European university
students: The e-MentH project.
AB - The aim of the present study was to describe the socio-demographic variables
associated with the use of the Internet for mental health information-seeking by
European university students, including participants' trust in the Internet, and
their use of the Internet in comparison to traditional formal mental health care.
A cross-sectional anonymous 25-item survey was conducted with 2466 students in
three courses (Computer Science, Law, Nursing) from four European universities
(France, Ireland, Italy, Spain). Participants were equally distributed in all
four countries; they were mostly females (57.5%), with a mean age of 21.6 years.
Overall, female, French and Nursing students were more likely to look for mental
health information. The majority (69.7%) of students reported that information
about mental health on the Internet was unreliable. Among all participants,
Spanish students reported a higher trust in web content. The findings suggest
that university students frequently use the Internet for mental health
information-seeking but not for mental health support. Furthermore, they do not
entirely trust the Internet for mental health-related issues. This should be
considered in planning Internet-based programmes for mental health promotion and
prevention in university students.
PMID- 29942559
TI - Exergames for the corporate wellness program in Singapore: An investigation of
employees' acceptance via watching Kinect video.
AB - Objective: This study aimed to explore the acceptance of exergames in a work
environment and investigate influencing factors through examining a conceptual
model. Methods: After viewing a short video on playing exergames, sixty recruited
working adults scored items associated with perceived usefulness, perceived ease
of use, attitude toward use, and intention to use. Confirmatory factor analysis
was carried out to test the measurement model, followed by structural equation
modeling to estimate the path coefficients. Results: The conceptual model was
generally supported, with most of the path coefficients being statistically
significant. Employees who perceived a higher level of ease of use toward
exergames are more likely to have higher perceived usefulness and attitude toward
use; higher perceived usefulness and attitude toward use further increases
employees' intention of use for the exergames. Conclusion: Findings emphasized
the importance of usability in affecting employees' acceptance of exergames,
thereby implying that designers should balance hedonic and utilitarian
considerations in game design.
PMID- 29942560
TI - Online support system for students in higher education: Proof-of-concept study.
AB - Background: Providing support to the increasing numbers of students facing mental
health difficulties in higher education (HE) can be difficult due to stigma or
lack of resources. Alternative and/or complementary sources of support are
needed, such as online interventions that are recognised for their therapeutic
value and cost-effectiveness. Objectives: We aim to provide evidence supporting
the conceptual and practical value of a newly developed online multimedia
intervention system for HE students who face mild to moderate symptoms of anxiety
and depression and study-skills difficulties. Methods: Students from five
universities were invited to participate in a cross-sectional proof-of-concept
study. Students were invited through the universities' internal communication
channels. Following demonstration of each part of the system, students completed
a survey with quantitative and qualitative questions. Results: Response was
largely positive. Positive responses on the features of the questionnaire ranged
between 65% and 86%; on the features of the workshops ranged between 57% and 91%;
on 'My place' ranged between 65% and 79%; on the animated videos ranged between
79% and 92%; and on the overall system ranged between 78% and 89%. Participants
indicated areas for improvement and ways in which such improvement could be
accomplished; these then guided the development of the system. Conclusions: The
results confirm the need for such a system. It can complement student support
services (SSS) by dealing with cases with mild to moderate difficulties, hence
allowing SSS to prioritise and effectively address more severe cases. Potentially
this method can provide a meaningful alternative to SSS; this is worth
investigating further.
PMID- 29942561
TI - Crowdsourcing for self-monitoring: Using the Traffic Light Diet and crowdsourcing
to provide dietary feedback.
AB - Background: Smartphone photography and crowdsourcing feedback could reduce
participant burden for dietary self-monitoring. Objectives: To assess if
untrained individuals can accurately crowdsource diet quality ratings of food
photos using the Traffic Light Diet (TLD) approach. Methods: Participants were
recruited via Amazon Mechanical Turk and read a one-page description on the TLD.
The study examined the participant accuracy score (total number of correctly
categorized foods as red, yellow, or green per person), the food accuracy score
(accuracy by which each food was categorized), and if the accuracy of ratings
increased when more users were included in the crowdsourcing. For each of a range
of possible crowd sizes (n = 15, n = 30, etc.), 10,000 bootstrap samples were
drawn and a 95% confidence interval (CI) for accuracy constructed using the 2.5th
and 97.5th percentiles. Results: Participants (n = 75; body mass index 28.0 +/-
7.5; age 36 +/- 11; 59% attempting weight loss) rated 10 foods as red, yellow, or
green. Raters demonstrated high red/yellow/green accuracy (>75%) examining all
foods. Mean accuracy score per participant was 77.6 +/- 14.0%. Individual photos
were rated accurately the majority of the time (range = 50%-100%). There was
little variation in the 95% CI for each of the five different crowd sizes,
indicating that large numbers of individuals may not be needed to accurately
crowdsource foods. Conclusions: Nutrition-novice users can be trained easily to
rate foods using the TLD. Since feedback from crowdsourcing relies on the
agreement of the majority, this method holds promise as a low-burden approach to
providing diet-quality feedback.
PMID- 29942562
TI - Who tweets about cancer? An analysis of cancer-related tweets in the USA.
AB - Cancer patients, family members and friends are increasingly using social media.
Some oncologists and oncology centres are engaging with social media, and
advocacy groups are using it to disseminate information and coordinate
fundraising efforts. However, the question of whether such social media activity
corresponds to areas with higher incidence of cancer or higher access to cancer
centres remains understudied. To address this gap, our study compared US
government data with 90,986 cancer-related tweets with the keywords 'chemo',
'lymphoma', 'mammogram', 'melanoma', and 'cancer survivor'. We found that the
frequency of cancer-related tweets is not associated with mammogram testing and
cancer incidence rates, but that the concentration of doctors and cancer centres
is associated with cancer-related tweet frequency. Ultimately, we found that
Twitter has value to cancer patients, survivors and their families, but that
cancer-related social media resources may not be targeting locations that could
see the most value and benefit. Therefore, there are real opportunities to better
align cancer-related engagement on Twitter and other social media.
PMID- 29942563
TI - When are medical apps medical? Off-label use and the Food and Drug
Administration.
AB - People have a love/hate relationship with rapidly changing healthcare technology.
While consumer demand for medical apps continues to grow as rapidly as does
supply (there are over 100,000 health, wellness and medical applications, or
'apps' on the market), healthcare professionals and safety experts worry about
the impact of these apps on the health consumer. In response to the rapidly
growing mobile healthcare sector, the Food and Drug Administration has put forth
guidelines to regulate 'mobile medical apps' (MMAs), those health-related apps
that are (self) designated as medical devices. In this article, I argue that this
decision, to only regulate apps that bill themselves as medical devices, will
create a market for 'off-label' app use. Further, I will talk about the oft used
analogy between off-label apps and off-label pharmaceuticals, showing that off
labeling apps will provide patients none of the benefits that come with a
physician prescribing a drug off-label, while exposing the mobile healthcare
consumer to significant risks that go significantly beyond those that we know of
(and must accept) from prescription drugs. Recognizing that the Food and Drug
Administration is not going to be able to significantly change its policies on
oversight, I will suggest specific actions to at least mitigate some of the risks
associated with off-label app use.
PMID- 29942565
TI - Improving performances of the emergency department using discrete event
simulation, DEA and the MADM methods.
AB - This article presents a method by which performances at an emergency department
(ED) in a large hospital in Iran could be improved, where the long waiting times
and unbalanced utilization create problems for patients and ED staff. This method
firstly simulates patient flow in the ED and finds bottlenecks that cause
inefficiency in ED performance. In the simulation model, patient arrival is
assumed to be non-homogenous and the operation of medical tests such as MRI, CT
scan, pathology testing, laboratory testing, ultrasonography, and radiology are
detailed and virtual queues of patients' specimens are considered separately from
patient queues. Based on the simulation reports of the current situation and
target criteria, what-if scenarios were used to design scenarios that could
improve ED performance. This method used the data envelopment method (DEA) to
determine efficient scenarios, analytic hierarchy process (AHP) to specify the
weight of each criterion, the Delphi method to specify suitable utilization rates
for various resources, and the extended Vlsekriterijumska Optimizacija I
KOmpromisno Resenje (VIKOR) method to compare data on 95% confidence intervals
from efficient scenarios and to rank scenarios by considering conflicting
criteria. Implementing the first scenario in the ranking would reduce acute
patients' overall waiting time by approximately 5%, and it doesn't require any
additional investments.
PMID- 29942564
TI - MedLink: A mobile intervention to improve medication adherence and processes of
care for treatment of depression in general medicine.
AB - Background: Major depressive disorder is a common psychological problem affecting
up to 20% of adults in their lifetime. The majority of people treated for
depression receive antidepressant medication through their primary care
physician. This commonly results in low rates of recovery. Failure points in the
process of care contributing to poor outcomes include patient non-adherence to
medications, failure of physicians to optimize dose and absence of communication
between patients and physicians. Objective: This pilot study evaluated the
feasibility of a systemic digital intervention (MedLink) designed to address
failure points and improve treatment of depression in primary care among patients
during the first eight weeks of initiating a new course of antidepressant
therapy. Methods: Participants were provided with the MedLink mobile app that
provided dose reminders, information and surveys of symptoms and side effects. A
cellularly enabled pillbox monitored antidepressant medication adherence. Reports
were provided to physicians and participants to prompt changes in medication
regimen. Study outcomes were assessed via self-report and interview measures at
baseline, week 4 and week 8. Results: Medication adherence detected by the
MedLink system was 82%. Participants demonstrated significant decreases in
depressive symptoms on the patient health questionnaire-9 (PHQ-9) (p = 0.0005)
and the Quick Inventory of Depressive Symptomatology (p = 0.0008) over the eight
week trial. Usability was generally rated favorably. Conclusions: The MedLink
system demonstrated promise as an intervention to address failure points in the
primary care treatment of major depressive disorder. Current findings support the
further development of MedLink through a randomized controlled trial to evaluate
the efficacy of improving processes of care, patient adherence and symptoms of
depression.
PMID- 29942566
TI - Internet use and health: Connecting secondary data through spatial
microsimulation.
AB - Objective: Internet use may affect health and health service use, and is seen as
a potential lever for empowering patients, levelling inequalities and managing
costs in the health system. However, supporting evidence is scant, partially due
to a lack of data to investigate the relationship on a larger scale. This paper
presents an approach for connecting existing datasets to generate new insights.
Methods: Spatial microsimulation offers a way to combine a random sample survey
on Internet use with aggregate census data and other routine data from the health
system based on small geographic areas to examine the relationship between
Internet use, perceived health and health service use. While health research has
primarily used spatial microsimulation to estimate the geographic distribution of
a certain phenomenon, this research highlights this simulation technique as a way
to link datasets for joint analysis, with location as the connecting element.
Results: Internet use is associated with higher perceived health and lower health
service use independently of whether Internet use was conceptualised in terms of
access, support or usage, and controlling for sociodemographic covariates.
Internal validation confirms that differences between actual and simulated data
are small; external validation shows that the simulated dataset is a good
reflection of the real world. Conclusion: Spatial microsimulation helps to
generate new insights through linking secondary data in a privacy-preserving and
cost-effective way. This allows for better understanding the relationship between
Internet use and health, enabling theoretical insights and practical implications
for policy with insights down to the local level.
PMID- 29942567
TI - A case study of stakeholder perceptions of patient held records: the Patients
Know Best (PKB) solution.
AB - Introduction: Patients Know Best (PKB) provides a patient portal with integrated,
patient-controlled digital care records. Patient-controlled personal health
records facilitate coordinated management of chronic disease through improved
communications among, and about, patients across professional and organisational
boundaries. An NHS foundation trust hospital has used PKB to support self
management in patients with inflammatory bowel disease; this paper presents a
case study of usage. Methods: The stakeholder empowered adoption model provided a
framework for consulting variously placed stakeholders. Qualitative interviews
with clinical stakeholders and a patient survey. Results: Clinicians reported PKB
to have enabled a new way of managing stable patients, this facilitated clinical
and cost effective use of specialist nurses; improved two-way communications, and
more optimal use of outpatient appointments and consultant time. The portal also
facilitated a single, rationalised pathway for stable patients, enabling access
to information and pro-active support. For patients, the system was a source of
support when unwell and facilitated improved communication with specialists.
Three main barriers to adoption were identified; these related to concerns over
security, risk averse attitudes of users and problems with data integration.
Conclusions: Patient-controlled personal health records offer significant
potential in supporting self-management. Digital connection to healthcare can
help patients to understand their condition better and access appropriate, timely
clinical advice.
PMID- 29942568
TI - Creating connections - the development of a mobile-health monitoring system for
heart failure: Qualitative findings from a usability cohort study.
AB - Objective: There is significant interest in the role of digital health technology
in enabling optimal monitoring of heart failure patients. To harness this
potential, it is vital to account for users' capacity and preferences in the
development of technological solutions. We adopted an iterative approach focussed
on learning from users' interactions with a mobile-health monitoring system.
Methods: We used a participatory mixed methods research approach to develop and
evaluate a mobile-health monitoring system. Fifty-eight heart failure patients
were recruited from three health care settings in the UK and provided with
Internet-enabled tablet computers that were wirelessly linked to sensor devices
for blood pressure, heart rate and weight monitoring. One to two home visits were
conducted with a subgroup of 29 participants to evaluate the usability of the
system over a median follow-up period of six months. The thematic analysis of
observational data and 45 interviews was informed by the domestication of
technology theory. Results: Our findings indicate that digital health
technologies need to create and extend connections with health professionals, be
incorporated into users' daily routines, and be personalised according to users'
technological competencies and interest in assuming a proactive or more passive
role in monitoring their condition. Conclusions: Users' patterns of engagement
with health technology changes over time and varies according to their need and
capacity to use the technology. Incorporating diverse user experiences in the
development and maintenance of mobile-health systems is likely to increase the
extent of successful uptake and impacts on outcomes for patients and providers.
PMID- 29942569
TI - Digital health citizens and the future of the NHS.
PMID- 29942570
TI - What do we need to consider when planning, implementing and researching the use
of alternatives to face-to-face consultations in primary healthcare?
AB - Objectives: Communications technologies are variably utilised in healthcare.
Policymakers globally have espoused the potential benefits of alternatives to
face-to-face consultations, but research is in its infancy. The aim of this essay
is to provide thinking tools for policymakers, practitioners and researchers who
are involved in planning, implementing and evaluating alternative forms of
consultation in primary care. Methods: We draw on preparations for a focussed
ethnographic study being conducted in eight general practice settings in the UK,
knowledge of the literature, qualitative social science and Cochrane reviews. In
this essay we consider different types of patients, and also reflect on how the
work, practice and professional identities of different members of staff in
primary care might be affected. Results: Elements of practice are inevitably lost
when consultations are no longer face-to-face, and we know little about the
impact on core aspects of the primary care relationship. Resistance to change is
normal and concerns about the introduction of alternative methods of consultation
are often expressed using proxy reasons; for example, concerns about patient
safety. Any planning or research in the field of new technologies should be
attuned to the potential for unintended consequences. Conclusions: Implementation
of alternatives to the face-to-face consultation is more likely to succeed if
approached as co-designed initiatives that start with the least controversial and
most promising changes for the practice. Researchers and evaluators should
explore actual experiences of the different consultation types amongst patients
and the primary care team rather than hypothetical perspectives.
PMID- 29942571
TI - A review of design characteristics of cognitive behavioral therapy-informed
behavioral intervention technologies for youth with depression and anxiety.
AB - Objective: Cognitive behavioral therapy (CBT) has the strongest evidence base for
the prevention and treatment of depression and anxiety in youth. Behavioral
intervention technologies (BITs) provide an opportunity to overcome access
barriers to traditional delivery of CBT. The present review evaluates the design
characteristics of CBT-informed BITs for depression and anxiety designed for and
tested with youth. Methods: A state-of-the-art review of three library databases
(PubMed, Scopus, and Web of Science) was conducted to identify papers that
evaluated the use of CBT-informed BITs for the prevention and/or treatment of
depression and anxiety among youth. Narrative results of design characteristics
were organized using the BIT model, which provides a framework for design and
evaluation. Results: 219 unique results were retrieved through the search. After
review, 14 papers (4 prevention and 10 treatment) met the selection criteria. A
broad diversity occurred in reporting the design and methodology of CBT delivered
to youth through BITs. Psychoeducation was overwhelmingly utilized as the primary
change strategy throughout the interventions, with a heavy use of content
delivery elements and linear workflows. The reporting of sample characteristics
was minimal and varied. Conclusions: Providing psychoeducation via content
delivery was the most utilized BIT change strategy in the interventions, likely
limiting the use of multiple BIT elements or flexible workflows. While
characterizations could be inferred from the current reports, the high level of
variability in reporting is problematic. Generalizability becomes increasingly
more difficult to carry out effectively without clear descriptions of the design
for evaluated BITs.
PMID- 29942572
TI - E-mental health special issue.
PMID- 29942573
TI - 'Pushed' self-tracking using digital technologies for chronic health condition
management: a critical interpretive synthesis.
AB - Introduction: Health policies internationally advocate health services provider
support for health services users' 'self-management' of chronic health
conditions. Digital technologies are beginning to have a role in delivering such
support. 'Pushed' self-tracking of health-related information, including imposed
measurement of biomedical and behavioural data, is one approach; however, there
is little systematic or discursive research. The aim of this research was to
explore factors relevant to the implementation of 'pushed' self-tracking
technologies into support for self-management of chronic health conditions
interventions. Methods: This paper reports a critical interpretive synthesis of
studies involving 'pushed' self-tracking using digital technologies to support
the self-management of chronic health conditions. The review systematically
identified relevant literature, characterised the technologies and discursively
explored their implementation and impacts, and human technology interactions.
Findings: The literature (n = 83), including 'simple' (n = 51) and 'complex' (n =
32) interventions, perhaps unsurprisingly, concentrates on technical and clinical
rather than sociological and behavioural perspectives, which limits
understanding. Some attention is paid to experiences and views of providers and
users about digital technologies implementation and impacts on the delivery of
care, for example: consequences of having increased information; compatibility
with current systems; implications for personnel; and human-technology
negotiations. Conclusions: This is a rapidly developing field and early technical
and clinical insights are useful. There are opportunities for researchers to
explore the sociological and behavioural aspects, and ethical challenges, of
implementing 'pushed' self-tracking support programmes too. Detailed
multidisciplinary research is needed to understand and guide technical and
medical developments that integrate digital technologies into the delivery of
care.
PMID- 29942574
TI - Understanding the use of contextual cues: design implications for medication
adherence technologies that support remembering.
AB - Objective: Forgetfulness is one of the main reasons of unintentional medication
non-adherence. Adherence technologies that help people remember to take their
medications on time often do not take into account the context of people's
everyday lives. Existing evidence that highlights the effectiveness of
remembering strategies that rely on contextual cues is largely based on research
with older adults, and thus it is not clear whether it can be generalized to
other populations or used to inform the design of wider adherence technologies
that support medication self-management. Understanding how younger populations
currently remember medications can inform the design of future adherence
technologies that take advantage of existing contextual cues to support
remembering. Methods: We conducted three surveys with a total of over a thousand
participants to investigate remembering strategies used by different populations:
women who take oral contraception, parents and carers who give antibiotics to
their children, and older adults who take medications for chronic conditions.
Results: Regardless of the population or the type of regimen, relying on
contextual cues-routine events, locations, and meaningful objects-is a common and
often effective strategy; combinations of two or more types of cues are more
effective than relying on a single cue. Conclusions: To effectively support
remembering, adherence technologies should help users recognize contextual cues
they already have at their disposal and reinforce relevant cues available in
their environment. We show that, given the latest developments in technology,
such support is already feasible.
PMID- 29942575
TI - The Men's Safer Sex Trial: A feasibility randomised controlled trial of an
interactive digital intervention to increase condom use in men.
AB - Objectives: We aimed to determine the feasibility of an online randomised
controlled trial (RCT) of the Men's Safer Sex website, measuring condom use and
sexually transmitted infection (STI). Methods: For this study 159 men aged >=16
with female sexual partners and recent condomless sex or suspected STI were
recruited from three UK sexual health clinics. Participants were randomised to
the intervention website plus usual clinic care (n = 84), or usual clinic care
only (n = 75). Online outcome data were solicited at 3, 6, and 12 months.
Results: Men were enrolled via tablet computers in clinic waiting rooms. Software
errors and clinic Wi-Fi access presented significant challenges, and online
questionnaire response rates were poor (36% at 3 months with a L10 voucher; 50%
at 12 months with L30). Clinical records (for STI diagnoses) were located for 94%
of participants. Some 37% of the intervention group did not see the intervention
website (n = 31/84), and (as expected) there was no detectable difference in
condomless sex with female partners (IRR = 1.01, 95% CI 0.52 to 1.96). New acute
STI diagnoses were recorded for 8.8% (7/80) of the intervention group, and 13.0%
(9/69) of the control group over 12 months (IRR = 0.75, 95% CI 0.29 to 1.90).
Conclusion: It is likely to be feasible to conduct a future large-scale RCT to
assess the impact of an online intervention using clinic STI diagnoses as a
primary outcome. However, practical and technical challenges need to be addressed
before the potential of digital media interventions can be realised in sexual
health settings.Trial registration number: ISRCTN18649610.
PMID- 29942577
TI - Virtual carers for the elderly: A case study review of ethical responsibilities.
AB - Intelligent digital healthcare systems are becoming an increasingly considered
approach to facilitating continued support of our ageing population. Within the
remit of such digital systems, 'Virtual Carer' is one of the more consistent
terms that refers to an artificial system capable of providing various assistive
living and communicative functionalities, embodied within a graphical avatar
displayed on a screen. As part of the RITA (Responsive Interactive Advocate)
project - a proof of concept for one such virtual carer system - a series of semi
structured discussions with various stakeholders was conducted. This paper
presents the results of these discussions to highlight data security, replacement
of human/physical care and always acting in the user's best interest. These three
ethical concerns and designer responsibilities are identified as highly relevant
to both individuals and groups that may, in the future, utilise a system like
RITA either as a care receiver or provider. This paper also presents some
initial, theoretical safeguard processes relevant to these key concerns.
PMID- 29942576
TI - Exploring the ambivalent evidence base of mobile health (mHealth): A systematic
literature review on the use of mobile phones for the improvement of community
health in Africa.
AB - Background: Africa is labelled the world's fastest-growing 'mobile region'.
Considering such growth and the fragility of the continent's healthcare, mHealth
has flourished. This review explores mHealth for community health in Africa in
order to assess its still ambivalent evidence base. Methods: Using PubMed, Web of
Science, OvidSP and Google Scholar, a systematic review was conducted of one
decade (2005-2015) of peer-reviewed literature on mHealth in Africa. Data
analysis focused on qualifications of success and failure. Impact evaluations of
project assessments (n = 65) were complemented with general analyses/overviews of
mHealth's effectiveness (n = 35). Results: Review of these texts reveals
ambivalence in the appraisal of mHealth; essentially, the critical stance in
general analyses/overviews is absent from project assessments. Especially weak
evidence concerning sustainability and scalability is stressed in overviews.
Project assessments are more optimistic. Their analysis suggests a causal
connection between simplicity and success. Effective interventions are thus
characterized by straightforward design and modest objectives. Greatest
impediments of impact are general technology-related issues and intervention
inappropriateness due to insufficient understanding of beneficiaries and specific
context of use (circumstantial complications). Conclusion: Distinguishing between
these two categories of complications helps to break the deadlock that marks the
mHealth debate and add nuance to claims that mHealth's evidence base is weak.
Constructive realism - rather than unfounded optimism or pessimism without nuance
- should guide the design of interventions. Besides anticipative of technology
related complications, such realism must lead to either basic interventions or to
smart mHealth shaped by deep understanding of the context of implementation.
PMID- 29942578
TI - Experiences of using a wearable camera to record activity, participation and
health-related behaviours: Qualitative reflections of using the Sensecam.
AB - Objective: Upcoming technology is changing the way that we are able to collect
data looking into activity, social participation and health behaviours. Wearable
cameras are one form of technology that allows us to automatically record a
collection of passive images, building a visual diary of the user's day. Whilst
acknowledging the usefulness of wearable cameras in research, it is also
important to understand individuals' experiences whilst using them. The aim of
this study was to explore the acceptance, experience and usability of a wearable
camera (Microsoft(r) Sensecam) to record the day-to-day activity and social
participation of older people. Methods: A total of 18 older adults, who had worn
the wearable camera for seven days, took part in semi-structured interviews.
Results: Four themes emerged from the findings: 'Intrusiveness'; 'Importance of
others'; 'Remembering the wearable camera'; and 'Ease of use'. Conclusions:
Individuals' expectations and experiences of using the wearable camera differed
considerably. Participants believed that the wearable camera would be intrusive,
difficult to use and would evoke public reaction; however, these worries were not
borne out in experience. Individuals typically forgot about the presence of the
wearable camera during use, remembering it only sporadically. One drawback to its
use is that some participants were cautious of using the camera when around
others, which impacted the amount of time the camera was worn, and, therefore,
the nature of the data recorded. Design issues of the Sensecam were also a
problem for the older adults in the study and affected their interaction with the
technology.
PMID- 29942579
TI - The 'who' and 'what' of #diabetes on Twitter.
AB - Social media are being increasingly used for health promotion, yet the landscape
of users, messages and interactions in such fora is poorly understood. Studies of
social media and diabetes have focused mostly on patients, or public agencies
addressing it, but have not looked broadly at all of the participants or the
diversity of content they contribute. We study Twitter conversations about
diabetes through the systematic analysis of 2.5 million tweets collected over 8
months and the interactions between their authors. We address three questions.
(1) What themes arise in these tweets? (2) Who are the most influential users?
(3) Which type of users contribute to which themes? We answer these questions
using a mixed-methods approach, integrating techniques from anthropology, network
science and information retrieval such as thematic coding, temporal network
analysis and community and topic detection. Diabetes-related tweets fall within
broad thematic groups: health information, news, social interaction and
commercial. At the same time, humorous messages and references to popular culture
appear consistently, more than any other type of tweet. We classify authors
according to their temporal 'hub' and 'authority' scores. Whereas the hub
landscape is diffuse and fluid over time, top authorities are highly persistent
across time and comprise bloggers, advocacy groups and NGOs related to diabetes,
as well as for-profit entities without specific diabetes expertise. Top
authorities fall into seven interest communities as derived from their Twitter
follower network. Our findings have implications for public health professionals
and policy makers who seek to use social media as an engagement tool and to
inform policy design.
PMID- 29942580
TI - Digital health and the biopolitics of the Quantified Self.
AB - Recent years have witnessed an intensive growth of systems of measurement and an
increasing integration of data processes into various spheres of everyday life.
From smartphone apps that measure our activity and sleep, to digital devices that
monitor our health and performance at the workplace, the culture of measurement
is currently on the rise. Encouraged by movements such as the Quantified Self,
whose motto is 'self knowledge through numbers', a growing number of people
across the globe are embracing practices of self-quantification and tracking in
the spirit of improving their wellbeing and productivity or charting their
fitness progress. In this article, I examine the biopolitical aspects of the
Quantified Self practices, exploring some of the ideologies and rationalities
underlying self-tracking culture. I argue that such practices represent an
instantiation of a 'biopolitics of the self' whereby the body is made amenable to
management and monitoring techniques that often echo the ethos of neoliberalism.
Rather than being restricted to an individualized form, self-tracking practices
are also becoming part of a biosocial and communal phenomenon in which
individuals are incited to share with others information about their physical
activities and biodata. In exploring some examples of this data sharing culture,
I critically address the extent to which the sharing of personal physical data
can be seen as a 'solidaristic' act that can contribute to a larger Big Data
ecosystem and inform the wider medical community and healthcare research and
policy. I link this discussion to debates on 'data philanthropy', highlighting
the emerging tension between philanthropic discourses of data sharing and issues
of privacy. From here, I go on to discuss further ethical and political concerns,
particularly in relation to data security and the marked shifts in healthcare
responsibilities.
PMID- 29942581
TI - Treatment choices for depression: Young people's response to a traditional e
health versus a Health 2.0 website.
AB - Objective: This exploratory experimental study compared young people's
credibility appraisals and behavioural intentions following exposure to
depression treatment information on a Health 2.0 website versus a traditional
website. The traditional website listed evidence-based treatment recommendations
for depression as judged by field experts. The Health 2.0 website contained
information about how helpful each treatment was, as aggregated from feedback
from young people with lived experience of depression. Method: Participants (n =
279) were provided with a vignette asking them to imagine that they had just
received a diagnosis of depression and they had gone online to find information
to guide their treatment choices. They were randomly allocated to view either the
traditional or the Health 2.0 website, and were asked to rate the credibility of
the depression treatment information provided. They were also asked to indicate
the extent to which they would be likely to act on the advice of the website.
Results: Participants in the traditional website condition rated their website as
significantly more influential than did participants presented with the Health
2.0 website. This difference in treatment influence was fully accounted for the
participants' perception of credibility of the information provided by the
websites. Conclusion: The traditional website was rated as significantly more
credible and influential than the Health 2.0 website. Treatment decisions
appeared to be based on the extent to which online information appears credible.
In conclusion, health-related content was perceived by users as more credible
when endorsed by experts than by other users, and perceived message credibility
appears to be a powerful determinant of behavioural intentions within the e
health setting.
PMID- 29942583
TI - Is knee pain information on YouTube videos perceived to be helpful? An analysis
of user comments and implications for dissemination on social media.
AB - Objective: There is little research that characterises knee pain related
information disseminated via social media. However, variances in the content and
quality of such sources could compromise optimal patient care. This study
explored the nature of the comments on YouTube videos related to non-specific
knee pain, to determine their helpfulness to the users. Methods: A systematic
search identified 900 videos related to knee pain on the YouTube database. A
total of 3537 comments from 58 videos were included in the study. A
categorisation scheme was developed and 1000 randomly selected comments were
analysed according to this scheme. Results: The most common category was the
users providing personal information or describing a personal situation (19%),
followed by appreciation or acknowledgement of others' inputs (17%) and asking
questions (15%). Of the questions, 33% were related to seeking help in relation
to a specific situation. Over 10% of the comments contained negativity or
disagreement; while 4.4% of comments reported they intended to pursue an action,
based on the information presented in the video and/or from user comments.
Conclusion: It was observed that individuals commenting on YouTube videos on knee
pain were most often soliciting advice and information specific to their
condition. The analysis of comments from the most commented videos using a
keyword-based search approach suggests that the YouTube videos can be used for
disseminating general advice on knee pain.
PMID- 29942582
TI - Expectancy, usage and acceptance by general practitioners and patients:
exploratory results from a study in the German outpatient sector.
AB - Objective: The study's objective was to assess factors contributing to the use of
smart devices by general practitioners (GPs) and patients in the health domain,
while specifically addressing the situation in Germany, and to determine whether,
and if so, how both groups differ in their perceptions of these technologies.
Methods: GPs and patients of resident practices in the Hannover region, Germany,
were surveyed between April and June 2014. A total of 412 GPs in this region were
invited by email to participate via an electronic survey, with 50 GPs actually
doing so (response rate 12.1%). For surveying the patients, eight regional
resident practices were visited by study personnel (once each). Every second
patient arriving there (inclusion criteria: of age, fluent in German) was asked
to take part (paper-based questionnaire). One hundred and seventy patients
participated; 15 patients who did not give consent were excluded. Results: The
majority of the participating patients (68.2%, 116/170) and GPs (76%, 38/50)
owned mobile devices. Of the patients, 49.9% (57/116) already made health-related
use of mobile devices; 95% (36/38) of the participating GPs used them in a
professional context. For patients, age (P < 0.001) and education (P < 0.001)
were significant factors, but not gender (P > 0.99). For doctors, neither age (P
= 0.73), professional experience (P > 0.99) nor gender (P = 0.19) influenced
usage rates. For patients, the primary use case was obtaining health (service)
related information. For GPs, interprofessional communication and retrieving
information were in the foreground. There was little app-related interaction
between both groups. Conclusions: GPs and patients use smart mobile devices to
serve their specific interests. However, the full potentials of mobile
technologies for health purposes are not yet being taken advantage of. Doctors as
well as other care providers and the patients should work together on exploring
and realising the potential benefits of the technology.
PMID- 29942584
TI - Impact of social media usage on daytime sleepiness: A study in a sample of
tertiary students in Singapore.
AB - Objective: Many tertiary students access social networking sites on a daily
basis. With the increased usage of smartphones, accessing social networking sites
while commuting, in schools, waiting for friends, television commercial breaks
has become prevalent among tertiary students. What started as a lifestyle choice
has now become a daily necessity. Such behavior among tertiary students raises an
important question for educators: how does social media usage affect tertiary
students' sleep patterns and daytime sleepiness, their attention difficulties,
especially in school? Thus, the aim of this study was to examine the
relationships between tertiary students' self-reports of social media usage and
daytime sleepiness. Design: The design was a cross-sectional, quantitative
research study. Methods: We used a survey that contained questions concerning
demographic data, daytime sleepiness, total sleep time and social media usage and
a version of the Cleveland Adolescent Sleepiness Questionnaire, modified for use
in tertiary students, were used for data collection (n = 969). Results: The most
preferred tool for accessing social networking sites was smartphones and WhatsApp
was the most accessed site. Results indicated that nocturnal technology use has a
weak, negative impact on tertiary students' quantity of sleep that may lead to
daytime sleepiness. Local Singapore students spent significantly more time on
social networking sites at night compared to foreign students. As a result, local
students experienced more daytime sleepiness compared to foreign students.
Conclusions: Prolonged social media usage, especially in bed, has a negative
impact on tertiary students' daytime sleepiness. Since the technology is such an
integral part of most tertiary students' lives, it is important to understand the
impact it has on their sleep and daytime sleepiness.
PMID- 29942585
TI - Making sense with sensors: Self-tracking and the temporalities of wellbeing.
AB - Self-tracking devices and apps often measure and provide interpretations of
personal data in a rather straightforward way, for instance by visualising the
speed and distance of a run or the quality of sleep during night. There is,
however, a growing number of devices claiming to support increased wellbeing by
extensive data analysis to provide insights and algorithmic advice about unseen
and neglected dimensions of our lives, bodies, and experiences. This article
engages with two devices of this kind, namely the Moodmetric and the OURA which
are two recently released 'smart' rings with associated smartphone apps that
claim to measure emotions and rest, promote happiness and help users to perform
better. Focusing on how certain values, visions and ideas are used to frame and
explain the potential functionality of these devices, this article approaches the
discursive underpinnings of their design as deeply intertwined with the
temporalities of late modernity. Empirically, the article is based on a discourse
analysis of blog posts, marketing materials and user guides from the OURA and
Moodmetric companies along with video recordings of the public appearances and
sales pitches of company representatives.
PMID- 29942586
TI - The use of social media by arthritis health professionals to disseminate a self
management program to patients: A feasibility study.
AB - Objective: The objective of this study was to determine the feasibility of
Facebook as a dissemination strategy for the People Getting a Grip on Arthritis
self-management program by arthritis health professionals to their patients.
Methods: The feasibility study comprised a single arm, pre-post design that
included a convenience sample of 78 arthritis health professionals across Canada.
Assessments were performed at baseline, two-weeks post-intervention, and at three
months follow-up using online questionnaires. The primary outcome measure was
change in perceived usability of Facebook as a dissemination strategy for the
People Getting a Grip on Arthritis program with patients at two-weeks post
intervention using an instrument based on an extended version of the Technology
Acceptance Model 2. Comparisons with baseline were assessed using t-test
analyses. Results: Statistically significant improvements from baseline were seen
for all items of the Technology Acceptance Model 2 domains: perceived ease of use
(four items), intention to use (two items) and output quality (two items)
domains. Variable results were seen for the job relevance, perceived usefulness,
voluntariness, and result demonstrability domains of the Technology Acceptance
Model 2. There were no statistically significant improvements for the subjective
norm and image domains. Conclusions: Facebook may provide arthritis health
professionals with an additional option of how to best share evidence-based
information to allow their patients to successfully self-manage their arthritis.
PMID- 29942587
TI - How does health feel? Towards research on the affective atmospheres of digital
health.
AB - The concept of affective atmospheres has recently emerged in cultural geography
to refer to the feelings that are generated by the interactions and movements of
human and nonhuman actors in specific spaces and places. Affective atmospheres
can have profound effects on the ways in which people think and feel about and
sense the spaces they inhabit and through which they move and the other actors in
those spaces. Thus far, very little research has adopted this concept to explore
the ways in which digital health technologies are used. As part of seeking to
redress this lacuna, in this essay I draw on previously published literature on
affective atmospheres to demonstrate and explain the implications of this
scholarship for future theoretical and empirical scholarship about digital health
practices that pays attention to their affective and sensory elements. The
article is structured into six parts. The first part outlines the concepts and
research practices underpinning affective atmospheres scholarship. In the second
part, I review some of the research that looks at place, space and mobilities in
relation to affective atmospheres. In the third part I focus more specifically on
the affective atmospheres of medical encounters, and then move on to digital
technology use in the fourth part. I then address in the fifth part, some
relevant scholarship on digital health technologies. I end the essay with some
reflections of directions in which future research taking up the concept of
affective atmospheres in the context of digital health technologies can go. The
key research question that these topics all work towards is that asking 'How does
digital health feel?'
PMID- 29942588
TI - Do health apps need endorsement? Challenges for giving advice about which health
apps are safe and effective to use.
PMID- 29942589
TI - 'This really takes it out of you!' The senses and emotions in digital health
practices of the elderly.
AB - Wearables, fitness apps and home-based monitoring technology designed to help
manage chronic diseases are generally considered in terms of their effectiveness
in saving costs and improving the health care system. This article looks,
instead, at the digital health practices of persons older than 65 years; it
considers their actual health practices, their senses and emotions. In a
qualitative study 27 elderly persons were interviewed about their digital health
practices and accompanied while using the devices. The findings show that digital
technologies and ageing bodies are co-productive in performing specific modes of
health and the ageing process. The study shows that digital technologies not only
encourage the elderly to remain physically active and enable them to age in
place, but also that the use of these technologies causes the elderly to develop
negative emotions that stand in a charged relationship to ageing stereotypes.
Thereby, the sense of seeing has been place in pole position, while the faculty
for introspection declines. This means that age-related impaired vision can
result in particularly severe consequences. In the discussion it is debated in
which concrete ways that digital health technologies have had a negative impact.
The sociotechnical practices associated with wearables conform to the primacy of
preventing ageing; passive and active monitoring technologies appear as
subsystems of risk estimation, which in turn regulates diverse practices. The
conclusion highlights the interrelation between notions of successful ageing and
the digital practices of the elderly.
PMID- 29942590
TI - Trading pounds for points: Engagement and weight loss in a mobile health
intervention.
AB - Objective: The objective of this study was to describe participant engagement and
examine predictors of weight loss and points earned through the point-based
incentive system of the Social Pounds Off Digitally (POD) app. Materials and
methods: Overweight and obese adults with Android smartphones/tablets (body mass
index 25-49.9 kg/m2; N = 24) were recruited for a 3-month weight loss
intervention. Participants completed a survey assessing demographics and
personality and had their weight measured. Participants received the content of
the intervention via podcasts and used the Social POD app to self-monitor diet,
physical activity, and weight. The Social POD app contained: tracking features;
in-app notifications to track; pre-set goals for tracking; newsfeed for updates
on others' goal attainment; ability to earn and track points for usage (exchanged
for study-provided prizes); and a message screen. Analyses examined relationships
between percent weight loss, personality characteristics, and total points
earned. Results: A total of 4843 points were earned (mean = 202 +/- 105
points/participant). Most participants earned all three prizes (62.5%), followed
by two prizes (21%), no prizes (12.5%), and one prize (4%). Total points earned
significantly predicted percent weight loss (B = -0.02, p = .01), and higher
conscientiousness significantly predicted greater total points earned (B = 10.27,
p = .01), but other personality characteristics assessed did not. Conclusion: A
mobile app yielded moderately high participant engagement, as demonstrated by
points earned. Earning points was significantly associated with percent weight
loss, and conscientiousness was significantly associated with total points
earned. Future research should examine whether point systems impact health
behavior and weight loss when rewards are discontinued. Clinical trial
registration number: NCT02344836.
PMID- 29942591
TI - Effectiveness and cost-effectiveness of a fully self-guided internet-based
intervention for sub-clinical social anxiety symptoms: Protocol for a randomised
controlled trial.
AB - Design and objective: This paper describes the protocol for a large-scale
pragmatic, randomised controlled trial and economic evaluation to investigate the
effectiveness and cost-effectiveness of the self-directed E-Couch social anxiety
module versus a waiting list control condition, for reducing sub-clinical social
anxiety symptoms in the general population. Study population: Community-based
adults (aged 18+) with social anxiety symptoms that do not meet the criteria for
social anxiety disorder recruited via a direct-to-consumer advertisement on
national websites. Intervention and control: Intervention is the self-guided E
Couch social anxiety module. Control group participants are placed on a waiting
list to receive the intervention at the end of the trial. Both groups receive
email and text message reminders. Outcome measures: The primary outcome will be
change in self-reported social anxiety score using the Social Phobia Inventory
(SPIN). Secondary outcomes will be the changes in the following self-report
measures: Brief Fear of Negative Evaluation scale (BFNE-S); depression (CES-D);
mental wellbeing (SWEMWEBS); health status (SF36); use of health services; safety
events; and adherence, retention, and attrition rates. All measures will be
administered at baseline, 6 weeks, and 3, 6 and 12 months. Analysis: A mixed
effects model will be used to analyse the effect of the intervention on the
primary and secondary outcomes (intention to treat analysis). Secondary analyses
will explore moderators and mediators of effect. A prospective economic
evaluation, conducted from a NHS and social care perspective, will provide
estimates of cost utility and cost-effectiveness. An interview study will be
conducted with 20 participants to explore issues including acceptability,
adherence, retention and attrition. Trial registration numbers: NCT02451878 and
ISRCTN15819951.
PMID- 29942592
TI - A framework for synthesis of safety justification for digitally enabled
healthcare services.
AB - Background: Digitally enabled healthcare services combine socio-technical
resources to deliver the required outcomes to patients. Unintended operation of
these services may result in adverse effects to the patient. Eliminating
avoidable harm requires a systematic way of analysing the causal conditions,
identifying opportunities for intervention. Operators of such services may be
required to justify, and communicate, their safety. For example, the UK
Standardisation Committee for Care Information (SCCI) standards 0129 and 0160
require a safety justification for health IT (superseded versions were known as
the Information Standards Board (ISB) 0129 & 0160. Initial as well as current
standards are maintained by the NHS Digital. Method: A framework was designed,
and applied as proof of concept, to an IT-supported clinical emergencies (A&E)
service. Evaluation was done qualitatively based on the authors' experience,
identifying potential benefits of the approach. Results: The applied framework
encapsulates analysis, and structures the generated information, into a skeleton
of an evidence-based case for safety. The framework improved management of the
safety activities, assigning ownership to stakeholders (e.g. IT developer), also
creating a clear and compelling safety justification. Conclusions: Application of
the framework significantly contributed to systematising an exploratory approach
for analysing the service, in addition to existing methods such as reporting. Its
application made the causal chain to harm more diaphanous. Constructing a safety
case contributed to: (a) identifying potential assurance gaps, (b) planning
production of information and evidence, and (c) communication of the
justification by graphical unambiguous means.
PMID- 29942593
TI - Challenges and opportunities in evaluating a digital sexual health intervention
in a clinic setting: Staff and patient views.
AB - Objectives: The aim of the study was to gather the views of sexual health clinic
staff and male clinic users regarding digital sexual health promotion and online
trial procedures. Methods: The Men's Safer Sex website was offered on tablet
computers to men in the waiting rooms of three sexual health clinics, in a
feasibility online randomised controlled trial (RCT). Interviews were conducted
with 11 men who had participated in the trial and with nine clinic staff, to
explore their views of the website and views of the online trial. Interviews were
audio-recorded and transcribed, and we conducted a thematic analysis of
interviews and of 281 free text comments from the online RCT outcome
questionnaires. Results: Clinic users and staff felt that digital interventions
such as the Men's Safer Sex website are useful, especially if NHS endorsed. Pre
appointment waiting time presents a good opportunity for intervention but clinic
users and staff felt that a website should supplement rather than replace face-to
face healthcare. The RCT procedures fitted well around clinical activities, but
men did not self-direct to the tablet computers. Staff were more concerned about
consent and confidentiality than clinic users, and staff and patients were
frustrated by multiple technical problems. The trial outcome questionnaire was
thought-provoking and could constitute an intervention in itself. Participants
felt that clinics would need to promote a digital intervention and/or offer the
site routinely to promote engagement. Conclusion: Digital interventions could
usefully supplement in-person sexual health care, but there are important
obstacles in terms of IT access in NHS settings, and in promoting engagement.
PMID- 29942594
TI - Usability testing of a smoking cessation smartphone application ('SmokeFree
Baby'): A think-aloud study with pregnant smokers.
AB - Background: Only a few digital interventions have been developed for pregnant
smokers, and little is known about the acceptability and usability of smartphone
apps to aid cessation in pregnancy. This study aimed to explore pregnant smokers'
views on the design, content and usability of a pregnancy-specific smoking
cessation app in order to inform intervention development and optimisation.
Methods: Ten interviews were conducted and the 'think-aloud' protocol was used in
order to explore participants' views about a smoking cessation smartphone app
('SmokeFree Baby'). The data were subsequently thematically analysed.
Participants were 18 and over, pregnant, and daily or weekly cigarette smokers.
Results: Three main themes were identified: views about the design elements, mode
of delivery and content of the intervention. App design was considered as an
important element that might influence potential users' engagement with the
intervention. Participants felt that the intervention content was educational,
motivational and non-judgemental. However, it was emphasised that the app should
provide further options for personalisation and include more practical features.
Conclusions: Delivering smoking cessation support via a smartphone app can be
feasible and acceptable for pregnant smokers. They appear to value content that
is motivational, educational and personalised, and meeting these requirements may
be important for user experience and promoting engagement with the intervention.
PMID- 29942595
TI - When support is needed: Social support solicitation and provision in an online
alcohol use disorder forum.
AB - Background: Obtaining adequate social support presents a challenge for many in
addiction recovery. Increasingly, individuals in recovery use online forums to
exchange support with peers, yet it is unclear which help-seeking strategies most
effectively recruit peer support, and which forms of support are most valued by
recipients. Methods: This study applied quantitative content analysis to examine
social support solicitation and delivery in an online forum for alcohol use
disorder (AUD). We compared the frequency with which peers provided
informational, emotional, and companionship support after solicitations that: (1)
were direct or indirect, (2) disclosed positive or negative emotions, and (3)
mentioned or did not mention recovery problems. We assessed likelihood that
recipients would express gratitude after receiving each type of support, and
assessed whether the "match" between solicitation and disclosure styles
influenced rates of gratitude expression. Results: Emotional disclosures, whether
positive or negative, received the highest volume of supportive replies.
Emotional support was the most common response to solicitations overall, and was
disproportionately offered after recipients disclosed positive emotions.
Informational support was disproportionately offered after recipients disclosed
negative emotions or recovery problems, or explicitly requested help. Regardless
of their solicitation style, recipients expressed more gratitude after receiving
emotional support than other support types. Conclusions: Providing emotional
support was common in an online AUD forum, and precipitated expressing gratitude
from recipients to support providers. The results may be helpful in guiding
participants to more effectively obtain and provide recovery support in online
forums.
PMID- 29942596
TI - Patient-perceived acceptability of a virtual world-based cardiac rehabilitation
program.
AB - Background: Despite its benefits, cardiac rehabilitation (CR) participation rates
remain subpar. Telehealth lifestyle interventions have emerged as modalities to
enhance CR accessibility. Virtual-world (VW) technology may provide a means to
increase CR use. Objectives: This pilot study assessed the feasibility and
acceptability of a VW-based CR program as an extension to medical center-based
CR. Our goal is to apply the study results toward the design of a patient
centered VW platform prototype with high usability, understandability, and
credibility. Methods: Patients (n = 8, 25% women) recently enrolled in outpatient
CR at Mayo Clinic, Rochester, Minnesota participated in a 12-week, VW health
education program and provided feedback on the usability, design and satisfaction
of the intervention at baseline and completion. A mixed-methods approach was used
to analyze the participant perceptions of the intervention. Results: Overall,
there were positive participant perceptions of the VW experience. There was
unanimous high satisfaction with the graphical interface appearance and ease of
use. Participants placed value on the convenience, accessibility, and social
connectivity of the remote program as well as the novelty of the simulation
platform presentations, which aided in memorability of key concepts. Greater than
80% of participants reported that the program improved their health knowledge and
helped to maintain better health habits. Conclusions: Our pilot study revealed
the feasibility and acceptability of an innovative VW-based CR program among
cardiac patients. This novel delivery method for CR has the potential to
influence healthy lifestyle change and to increase accessibility to vulnerable
populations with higher cardiovascular disease burdens.
PMID- 29942597
TI - A text message intervention to reduce first year university students' alcohol
use: A pilot experimental study.
AB - Objective: The aim of Orientation Week is to help new students acclimatize to
university life. However, Orientation Week is characterized by heavy alcohol use
and during this time students may develop drinking patterns that persist into the
academic year. The aim of the current study was to refine a brief Ecological
Momentary Intervention (EMI) and test its effectiveness in reducing students'
alcohol use during both Orientation Week and throughout the academic year.
Method: We conducted two focus groups with students who had received a pilot
intervention. We then updated and trialled the intervention with students from
two residential colleges (College 1 n = 117 and College 2 n = 269) who were
assigned to either an Ecological Momentary Assessment (EMA) condition or an EMA
EMI condition. Students in both conditions reported their pre-university drinking
and their drinking during Orientation Week and the academic year via text
message. In addition to the EMA messages, during Orientation Week, participants
in the EMA-EMI condition received messages highlighting the potential social
consequences of heavy alcohol use. Results: In College 1 those in the EMA-EMI
condition consumed fewer drinks, relative to those in the EMA condition, across
both Orientation Week (9.7 vs. 15.5; t(98) = 2.138, p = .018) and the academic
year. (4.3 vs. 6.8; t(98) = 1.788, p = .039). There were, however, no significant
differences between conditions in College 2. Conclusion: The current findings
suggest that EMIs may be successful under certain circumstances and may provide a
simple, cost-effective means of intervening.
PMID- 29942598
TI - What we see when we digitize pain: The risk of valorizing image-based
representations of fibromyalgia over body and bodily experience.
AB - Fibromyalgia is chronic pain of unknown etiology, attended by fatigue and
affective dysfunction. Unapparent to the unpracticed eye or diagnostic image, it
is denied the status of "real" suffering given to visually confirmable disorders.
It is my customary mode of existence: a contingent landscape of swinging bridges
that may or may not give way, everything a potential threat or deprivation. I
don't express it within the framework of acute pain, but I am evaluated by
traditional biomedical standards anyway. Ultimately, the diagnostic image of
pain, and the medical and academic discourse used to interpret it, determines my
functionality. Such a stance dismisses bodily senses and alternate ways of
knowing in pursuit of the ocularcentric objectivity promised by digital health
technologies, whose vision remains chained to the interpretive, discursive
strategies of human operators and interpreters. A new poetics of pain is critical
not only for rewriting the dominant metaphors that construct and delimit our
imaginings of pain but also for rewiring the use and reading of digital
technologies, wherein the digital image becomes the new site of the hermeneutic
exercise, even when the suffering body lies in plain view. This facilitates a
failure to listen and touch in patient care, and the imposition of a narrative
based on visual evidence, translated into sanitized language, at the cost of
intercorporeality. If pain strips sufferers of a voice, my body and its affects
should be allowed to speak.
PMID- 29942599
TI - Layers of sense: the sensory work of diagnostic sensemaking in digital health.
AB - Sensory judgements have always been a part of medical practice and this sensory
work is often entangled with technologies, from the stethoscope to digitised
devices for advanced life support. This article investigates this sensory work
and its entanglements with technological sensors in diagnostic practice. Based on
semi-structured interviews, it presents a close analysis of practitioners' use of
anaesthetic monitoring and telemedicine. It argues that senses and sensors are
recursively combined in the moment towards understanding. In this, digital
technologies do not present self-evident data, but rather the practitioner must
learn to sense the sensors to interpret health and illness. Sensory work (of both
the senses and sensors) is not dispensable or entirely delegable because it is
intimately entwined with sensemaking. The significance of sensory work to
sensemaking reinforces the importance of its consideration in digital health
sociotechnical assemblages.
PMID- 29942600
TI - Mobilizing social media users to become advertisers: Corporate hashtag campaigns
as a public health concern.
AB - Objective: With the growing popularity of social media, corporate marketers are
increasingly launching hashtag campaigns to encourage consumers to create branded
user-generated content on their behalves. If successful, these campaigns may
expand the reach of harmful marketing messages and capitalize on peer-effects
among adolescents. To shed light on these novel corporate campaigns, we performed
a case study of the user-generated Instagram content created in response to a
hashtag campaign promoting the quick-service restaurant Kentucky Fried Chicken
(KFC). Methods: We performed a content analysis of one week's worth of user
generated Instagram posts created with the hashtag #HowDoYouKFC between 24 April
2015-1 May 2015. Posts were coded to discern: (a) relevance to KFC as a brand
and/or food; (b) themes in the post, (c) the content of images/videos, and (d)
overall sentiment toward KFC. Posts that were deleted or made private during the
study period were removed. Descriptive statistics were calculated to discern
trends in post content. Results: Instagram users created 196 posts with
#HowDoYouKFC during the study period. After removing irrelevant and
deleted/private posts, analysis of the 128 remaining user-generated posts
revealed that 45% of posts were explicitly positive toward KFC and 39% lacked a
specific stance or emotion related to KFC. Of the posts, 55% depicted KFC chicken
and 65% included depictions of the brand hashtag on food packaging. Conclusions:
Findings indicate that corporations are successfully converting individual social
media users into positive advertisers for harmful products. Novel efforts are
needed to counter corporate user-generated content campaigns.
PMID- 29942601
TI - Exercise monitoring of young adults using a Facebook application.
AB - Facebook, with a record 1.7+ billion monthly active users, is increasingly the
platform of choice for a multitude of e-health applications. This work presents
our experience in exercise monitoring using a custom-built Facebook application
for activity self-reporting. A group of young adults (n = 49, age = 24 +/- 7
years, body mass index (BMI) = 22.5 +/- 3) took part in a 5-week pilot study,
part of the NutriHeAl intervention project. Participants reported their daily
exercise activities for an average of 33 +/- 5 days and were also equipped with
digital pedometers (Fibit Zips) for the full duration, allowing the evaluation of
their activity reporting accuracy by comparing steps/min to a 'truth ceiling'
value for two pre-defined exercise categories (2 + and 3+ metabolic equivalent of
task (MET) intensity). We found that users not only reported their exercise
consistently for an extended period of time but also achieved an average accuracy
score of 71 +/- 21% (82 +/- 18% for 2+ MET exercises), making this novel exercise
monitoring methodology a formidable tool for a modern physician's digital
arsenal. In addition, the developed tools and processes can also be re-used in
other e-health applications.
PMID- 29942602
TI - Co-constructed health narratives during a 'media event': The case of the first
Dutch Twitter heart operation.
AB - Objective: This article examines the relationship between microblogging and the
development of health narrative through the lens of an institution-initiated
media event, the first live-tweeted heart operation in the Netherlands. It
specifically addresses the question, how does health narrative take shape on a
microblog and other (social) media, through the combination of self-initiated
status updates, reactions to questions and short conversations with followers?
Methods: A combination of qualitative and quantitative data analysis was used to
identify prominent themes in the tweets and trace the complex process by which
the narrative took shape. The results presented here are derived from the
qualitative analysis. Results: There are four recurring health narrative themes
in the tweets: (a) new challenges to professionalism; (b) mutual exchanges of
information, support and advice; (c) increasingly personal (and public) details;
and (d) questions about 'resuming normalcy'. The special nature of this case also
reveals interesting features, such as the multiple narrative starting points and
the phenomenon of 'tweeting by proxy', and raises a number of critical questions
regarding this type of use of social media in healthcare. Conclusions: In the
discussion we reflect on whether/how microblogged health narratives are really
'new' and on the implications of this single case for understanding the
relationship between social media, health narrative and the changing
relationships between information technologies, actors and institutions. We
further examine this case as an example of what Lupton has deemed the 'digital
patient experience economy', in reference to patients increasingly being
encouraged to post experiences of their illness and encounters with the
healthcare system to online platforms, where these shared experiences become
valorised and monetised.
PMID- 29942603
TI - Help seeking for social anxiety: A pilot randomised controlled trial.
AB - Objective: Although social anxiety disorder is a persistent and debilitating
condition, only a minority of people with social anxiety disorder seek help and
little is known about methods for promoting help seeking for social anxiety
disorder. This pilot trial explored the potential effectiveness of an online
program designed to increase help-seeking intentions for social anxiety disorder.
Methods: Australian adults with symptoms of untreated social anxiety disorder
were recruited online and randomised to either the Shyness Information Online
intervention (n = 41) or an online attention control condition (n = 41). Each
program together with a baseline and postintervention survey was delivered in one
session. The primary outcome was intentions to seek help from a professional.
Secondary measures included anxiety literacy, help-seeking attitudes,
internalised stigma, and perceived need for treatment. The acceptability of the
program content and feasibility of the recruitment method were also examined.
Results: Although they did not demonstrate a significantly greater increase in
help-seeking intentions relative to the control group (p = 0.097), those
receiving the intervention showed more favourable attitudes towards seeking
psychological help (Hedges'g = 0.38; p = 0.025) and a higher level of perceived
need for treatment (p <= 0.001). Participants also showed a greater knowledge
about social anxiety disorder at post-intervention than the control participants
(adjusted Hedges' g = 0.46, p < 0.001). Most respondents were satisfied with the
intervention content; the recruitment strategy appeared feasible. Conclusions:
Further investigation of the intervention is warranted to test its effectiveness,
explore the relationships between factors that influence social anxiety disorder
help-seeking behaviour and to further test the validity of the social anxiety
disorder help-seeking model on which the intervention was based.
PMID- 29942604
TI - Living the metrics: Self-tracking and situated objectivity.
AB - This paper evaluates self-tracking practices in connection with ideas of
objectivity via exploration of confrontations with personal data, particularly
with reference to physiological stress and recovery measurements. The discussion
departs from the notion of 'mechanical objectivity', seeking to obtain evidence
that is 'uncontaminated by interpretation'. The framework of mechanical
objectivity tends, however, to fall short when people translate physiological
measurements to fit their expectations and everyday experiences. We develop the
concept of 'situated objectivity' with the goal of highlighting the everyday as a
domain of interpretation, reflection and ambiguity, proposing that the concept
offers an analytical entry point to a more profound understanding of how people
engage with their personal data. Everyday data encounters are not methodical and
systematic, but combine knowledge in an eclectic manner. Framed in this way, self
tracking practices are less occupied with 'facts of life' than translating and
transforming life based on earlier experiences, cultural understandings and
shared expectations. Paradoxically, new measurement devices and software, which
are supposed to be based on sound, universal and generalisable principles, hard
facts and accurate descriptions, become raw material for daily decisions, as
people seek bespoke answers and craft personalised theories of health and life.
From this perspective, self-tracking measurements can be used to experiment and
learn, gaining value in relation to the communicative processes that they promote
and contributing to possibilities for rethinking health knowledge and health
promotion.
PMID- 29942606
TI - Acceptability and willingness to pay for telemedicine services in Enugu state,
southeast Nigeria.
AB - Background: This study examines the level of awareness, acceptability and
consumers' willingness to pay (WTP) for telemedicine services using the
contingent valuation method (CVM). This work is important as it elicits the value
that consumers attach to telemedicine given there is a gap in this knowledge in
many sub-Saharan countries such as in Nigeria. Methods: The study was based on
primary data obtained through an interviewer-administered questionnaire of 370
individuals including both males and females from 25 years and over, to collect
data on respondents' awareness of, acceptability of, and WTP for telemedicine,
using the bidding game question format. A socioeconomic status (SES) index was
created, based on information on household assets, and was used to categorize
respondents into SES quartiles. The data were analyzed using a combination of
descriptive techniques, logistics and the Tobit regression model (Tobit Type 1)
methods. Results: The study found that majority of the people (58.9%) had no
knowledge of telemedicine. However, 48.7% of the respondents were willing to pay
for telemedicine. The mean WTP for a telemedicine was US$2.04 for each visit.
Tobit regression analysis showed that respondents' socioeconomic status (SES) was
the main statistically significant variable that explained their WTP for
telemedicine. Conclusion: The study has shown that there is a low-level awareness
of and WTP for telemedicine services in Enugu State, South East of Nigeria. The
finding of a positive relationship between SES and WTP implies that the poor may
not be able to pay for telemedicine and may need government subsidies to be able
to benefit from such service. Also, government and their partners need to
undertake wide scale campaign before the introduction of telemedicine.
PMID- 29942605
TI - What might get in the way: Barriers to the use of apps for depression.
AB - Objective: Smartphones are being used with increasing frequency to deliver
behavioral interventions for depression via apps. However, barriers specific to
using an app for depression are poorly defined. The purpose of the current study
is to identify barriers to the use of a mobile app to deliver treatment for
depression. Secondarily, design implications will be provided based upon
identified barriers. Method: A card sorting task that ranked and grouped barriers
to the use of apps for depression was completed. Participants first completed a
card sorting task identifying barriers to face-to-face treatment, as a primer to
identification of treatment barriers. The sample consisted of those above (n = 9)
and below (n = 11) the threshold for a referral to psychotherapy, to capture
anticipated barriers for likely end users. Cluster analyses were conducted to
analyze the card sorting data. Multiple analyses were conducted to identify: 1)
the most important barriers, and 2) how consistently barriers were ranked as
important. Result: The card sorting task identified a number of primary barriers
to the use of apps for depression treatment, including concerns over intervention
efficacy, app functioning, privacy, cost, and lack of guidance and tailored
feedback. The top face-to-face treatment barrier was cost, overlapping with
mobile barriers. Conclusion: This study identified perceived barriers to the use
of mobile treatment apps. Identification of barriers implicates design
recommendations for apps for depression.
PMID- 29942607
TI - The feasibility of delivering constraint-induced language therapy via the
Internet.
AB - Objective: This study is designed to determine the feasibility of the provision
of an evidenced-based aphasia therapy, constraint-induced language therapy, via
telerehabilitation. It describes the computer software that was developed
specifically for the delivery of constraint-induced language therapy in the
online environment and presents two case studies. Methods: Two participants with
chronic aphasia were assessed before and after a two-week intensive treatment
block of constraint-induced language therapy delivered via Web-based
videoconferencing. The group-based, dual card request game utilized in face-to
face constraint-induced language therapy was transformed into an innovative and
user-friendly Web-based game - Internet constraint-induced language therapy
(iCILT). Participants accessed iCILT via the Internet from their own home every
weekday for two weeks. Language and quality of life measures were administered
pre- and post-therapy in order to detect treatment effects. Participant
satisfaction information was also recorded. Results: Online delivery of iCILT was
technically feasible and participant satisfaction was high with a number of
benefits associated with telerehabilitation identified by participants. Post
treatment performance for language functioning and communication-related quality
of life was variable for each participant, however improvements in naming were
noted. Conclusions: Constraint-induced language therapy delivered via
telerehabilitation may be a feasible alternative to traditional face-to-face
therapy for people with chronic aphasia.
PMID- 29942608
TI - Internet-based Interacting Together Everyday, Recovery After Childhood TBI (I
InTERACT): Protocol for a multi-site randomized controlled trial of an internet
based parenting intervention.
AB - Objectives: We discuss the rationale and description of the Internet-Based
Interacting Together Everyday, Recovery After Childhood TBI (I-InTERACT), a
telehealth intervention designed to promote positive parenting skills through
live in-session skills practice and coaching. A second objective is to describe
the protocol of a three-armed (Internet Resource Comparison, I-InTERACT, and I
InTERACT Express) multi-site randomized controlled trial (RCT) designed to
examine intervention effectiveness. Method: Participants included parents of
children ages 3-9 who sustained a moderate or severe traumatic brain injury (TBI)
any time since birth. Measures assessing parenting behaviors, parent-child
interaction, parent/family factors, and child factors were collected prior to
intervention, 3 months after enrollment and 6-months after enrollment. Results:
This protocol manuscript was submitted before the completion of data collection
and prior to any data analysis. It is expected that the I-InTERACT and I-InTERACT
Express interventions will be associated with an increase in positive parenting
behaviors, and a decrease in negative parenting behaviors, parental distress, and
child behavior problems. Finally it is expected that socioeconomic status, life
stressors, and social resources will moderate treatment effects. Conclusions: The
study described in this protocol paper represents one of the first large multi
site RCTs of a parenting intervention designed to promote positive parenting
skills in families with young children who sustained a TBI. We plan to
disseminate findings to patients and families as well as clinical and research
professionals, and begin to develop a research base for this telehealth
intervention.
PMID- 29942609
TI - When self-tracking enters physical rehabilitation: From 'pushed' self-tracking to
ongoing affective encounters in arrangements of care.
AB - In this paper, I explore what happens when self-tracking technologies and devices
travel into the context of physical rehabilitation and come to constitute what
Lupton has called 'pushed' self-tracking. By unpacking the processes through
which a self-tracking technology is put to use in physical rehabilitation in
Denmark, and the kind of relationships patients and healthcare providers
establish with and through this technology, I illustrate how a new geography of
responsibility is constituted, where responsibility for professional guidance is
delegated to the technology and patients are expected to produce and engage in
movement data. In contrast to the image of 'pushing' as a single activity where
one part (technology) has the authority to push the other (patient) to act in
certain ways, I argue that 'the push' is better described as an ongoing and
contingent process that evolves through affective and affecting encounters
between human (patients, healthcare providers) and nonhuman (technology,
algorithms, software) actors. I illustrate that even though responsibility is
delegated to the technology, it is unable to make bodies move by itself. Rather,
what determines what 'it' becomes and how 'it' comes to act is enabled by the
constitution of a wider arrangement of care and the arrangements' ability to
affect and respond to particular bodies.
PMID- 29942611
TI - VIEWPOINT: What counts as online patient feedback, and for whom?
PMID- 29942610
TI - Exploring the acceptability and feasibility of a preconception and diabetes
information app for women with pregestational diabetes: A mixed-methods study
protocol.
AB - Background: Women with diabetes are at increased risk of adverse maternal and
fetal outcomes. Preconception care can improve pregnancy outcomes and is
paramount to minimise complications, but, current provision is sub-optimal.
Mobile technology, particularly smartphones and apps have the potential to
improve preconception care provision but research is lacking in this area. The
need to use modern technologies to improve preconception care knowledge and
awareness led to the development of a preconception and diabetes information app
in Stage A of this study. Objective: The aim of this paper, Stage B of the study,
is to explore the feasibility and acceptability of the Preconception and Diabetes
Information app to improve preconception care knowledge and attitudes in women
with diabetes, and explore the potential for wider implementation. Methods: A
mixed-methods study design adopting a quasi-experimental approach will assess
women's knowledge and attitudes related to preconception care, and level of
patient activation (knowledge and confidence for self-management of health)
before and after the three-month intervention period. A log of activity will be
used to determine engagement with the app and semi-structured interviews will
explore women's experiences. Conclusions: This is the first study to explore the
acceptability and feasibility of a preconception and diabetes information app for
women with diabetes. The app has potential to change the way preconception care
is delivered, improve pregnancy outcomes and be widely implemented both in
developed and developing countries. This is important given the considerable
shortfalls in current preconception care services in the United Kingdom and
around the world.
PMID- 29942612
TI - Measurements of glucose concentration in aqueous solutions using reflected THz
radiation for applications to a novel sub-THz radiation non-invasive blood sugar
measurement method.
AB - The terahertz (THz) frequency range corresponds to molecular vibrations or
relaxation modes such as those for the hydrogen bond. Most biomolecules are
activated only in aqueous solutions, thus, to understand the function and
structure of biomolecules, it is necessary to investigate the characteristics of
electromagnetic waves in hydrated samples. THz radiation causes little damage to
the human body, thus it is expected that it can be applied for noninvasive
examinations. However, spectrometry of the transmitted light is difficult, since
the absorption of THz radiation in water is extremely high. In this study, we
used sub-THz radiation (frequencies near to 0.1 THz), where the absorption is
lower than for THz radiation, to measure the reflectance of a glucose water
solution. We found that the reflectance decreases in proportion with the glucose
concentration. These results suggest that sub-THz radiation can be used in the
noninvasive measurement of blood glucose levels.
PMID- 29942613
TI - Using SmartQuit(r), an Acceptance and Commitment Therapy Smartphone application,
to reduce smoking intake.
AB - Objective: SmartQuit(r) is a smartphone application (app) for smoking cessation
based on Acceptance and Commitment Therapy, a behavioural therapy that encourages
individuals to accept internal experiences, such as cravings to smoke, without
acting on those experiences or urges. We used a single-subject (A-B-A) design
with 10 participants to examine whether SmartQuit(r) use would reduce cigarette
intake in a New Zealand sample. Methods: 10 smokers tallied their own cravings
experienced and cigarettes smoked then sent those tallies to the first author
every day until we observed stable patterns (Phase A1). We then gave the
participants individual access to the SmartQuit(r) app (Phase B). When they
advised that they had ceased using the app, they again recorded daily cravings
and cigarettes smoked for a minimum of three days (Phase A2). We also collected
follow-up smoking and craving data at 1, 2 and up to 13 months after completion
of Phase A2. Results: Using SmartQuit(r) reduced our participants' daily
cigarette intake significantly in the short-term and three individuals remained
smoke-free up to 13 months later. Cravings to smoke did not differ significantly
across Phases A1, B and A2, but graphical analysis showed a trend for decreasing
cravings. Conclusion: Our results suggest that SmartQuit(r) provides another
readily accessible intervention to help people stop smoking and is suited for use
with a New Zealand population.
PMID- 29942614
TI - The effect of programme testimonials on registrations for an online cognitive
behaviour therapy intervention: a randomised trial.
AB - Objective: Suboptimal visit-to-registration rates limit the reach and potential
impact of online health interventions. In this study, we examined whether
testimonials presented during a new-user registration process could increase the
uptake rates of MoodGYM, an open-access automated intervention designed to reduce
the symptoms of depression. Methods: We conducted a three-armed parallel
randomised controlled trial on the MoodGYM website involving variations of the
first page of the registration process. Spontaneous visitors saw either the
current pre-registration content, the current content supplemented by a first
person past user testimonial or the current content accompanied by a testimonial
from a third-party health professional. The primary outcome measure was the
proportion of visitors seeing each version who completed registration. Results: A
total of 14,267 visits were recorded across the three conditions. The past user,
health professional and control condition registration rates were 45.6%, 45.5%
and 45.5% respectively, indicating that there was no effect of registration
content on registration rate. (p > 0.05). Conclusions: There may be limited use
for testimonials in well-established interventions that have programme benefits
clearly stated and presented in other forms. However, we cannot exclude the
possibility that testimonial effects might be moderated by positioning or other
elements within the registration flow or by visitor source. Further research is
required to examine these factors and, more broadly, assess whether modifications
to other aspects of the registration process can improve visit-to-registration
rates.
PMID- 29942615
TI - Acceptability of targeting social embarrassment in a digital intervention to
reduce student alcohol consumption: A qualitative think aloud study.
AB - Objective: Increasing knowledge about alcohol-related harms, changing social
norms, or encouraging drinking within safe unit levels often fails to change
behaviour in young people. A novel intervention called 'OneTooMany' was
developed, which targets the short-term social, and potentially, embarrassing
consequences of drinking alcohol. The aim of this paper was to explore its
acceptability, and to determine any features that might influence its
effectiveness as a means of reducing alcohol consumption. Methods: Participants
were 23 young adults (aged 18-30) currently studying at university (n = 18) or in
the first six months following graduation (n = 5). A think aloud interview
approach was employed. Three main themes were identified in a deductive thematic
analysis. Results: Embarrassing experiences were a normalised part of drinking
occasions, while some were actively avoided, others were celebrated. Humour
served as a device to engage and interest participants, but could also diminish
intervention messages. OneTooMany prompted reflections on many regrettable
drinking experiences, but the participants did not see themselves as the target
audience for this intervention. Conclusions: Interventions may benefit from
focusing on some of the short term, embarrassing consequences of excessive
alcohol consumption. Further research is needed to ensure that reflections on
past behaviour are helpful in addressing future behaviour.
PMID- 29942616
TI - Digital health now and in the future: Findings from a participatory design
stakeholder workshop.
AB - Objectives: While digital health technologies hold potential for improving
healthcare and the generation and dissemination of health information, there are
many issues to be resolved in facilitating their provision and efficacy and
ensuring ethical management of personal health data. In the face of high-stakes
digital health initiatives, debates and controversies, eliciting the views and
experiences of the diverse constituents in the digital health ecosystem is
important. Methods: A digital health stakeholder workshop was held in Canberra,
Australia, to address two key questions: 1) What is currently working and not
working in digital health? and 2) Where should digital health go in the future?
As part of a living lab approach, the 25 workshop participants from research,
industry, patient and other healthcare consumer groups and government, engaged in
participatory design activities directed at stimulating ideas and discussion. The
design artefacts and videos generated during the workshop were thematically
analysed. Results: Digital health technologies offer valuable ways for healthcare
consumers, providers, community groups and health industries to create and share
information about health, medicine and healthcare. However, members of some
social groups are currently excluded from full participation in the digital
health ecosystem. Mechanisms for facilitating further consultation between the
various stakeholders involved in digital health, including patients and carers,
need to be established. The rights and responsibilities of the different
stakeholders involved in connected digital health also need to be better
identified and highlighted. At the same time, personal data privacy and security
need protection. Conclusion: Establishing the effective and responsible delivery
of digital health technologies and collection, protection and sharing of health
data is highly complex. Infrastructure, ethical and social issues need to be
considered.
PMID- 29942617
TI - The use of mobile devices for physical activity tracking in older adults'
everyday life.
AB - Objective: The tracking of one's own physical activity with mobile devices is a
way of monitoring and motivating oneself to remain healthy. Older adults' general
use of mobile devices for physical activity tracking has not yet been examined
systematically. The study aimed to describe the use of physical activity
trackers, smartwatches and smartphones, or tablets for tracking physical activity
and to examine the reasons for the use of these technologies. Methods:
Participants aged >=50 years (N = 1013) living in Switzerland were interviewed in
a telephone survey. To address the research questions, we calculated descriptive
frequency distributions, tested for differences between groups, and performed
logistic regression analyses. Results: Descriptive and multivariate analyses
showed that (a) 20.5% of participants used mobile devices for physical activity
tracking; (b) men, younger individuals, those with a strong interest in new
technology, and those who frequently exercised had a higher likelihood of using
mobile devices for physical activity tracking; and (c) participants more often
agreed with reasons for use relating to tracking physical activity and motivating
oneself to remain healthy than they did with reasons relating to social factors.
Conclusions: The study presented representative data about the actual use of
mobile tracking technology in persons over 50 years of age. Today, mainly active
and younger elderly (mostly men) with a high interest in technology are using
tracking technologies. Results indicate a need for further studies on
motivational and usability aspects regarding the use of mobile health tracking
devices by older adults.
PMID- 29942618
TI - Digital health evaluation workshop for interprofessional healthcare students.
AB - The use of online resources by patients for their daily health needs has
escalated with the proliferation of mobile devices and mobile apps. While
healthcare professionals can help their patients access quality online resources
and tools, they may not have received the education and training to do this
effectively. To meet this educational need, a daylong workshop was developed at a
health sciences university that aimed to increase awareness of students in
various health disciplines of mobile health-related apps and federally sponsored
websites that provide patient-friendly medical information.
PMID- 29942619
TI - Editorial: Towards sensory studies of digital health.
PMID- 29942620
TI - The effectiveness of text message-based self-management interventions for poorly
controlled diabetes: A systematic review.
AB - Background: Poorly controlled diabetes leads to debilitating complications at a
significant cost to health systems. Text messaging is an ideal platform for the
delivery of self-management interventions to patients with poorly controlled
diabetes due to the ubiquity of mobile phones, and the ability of text messaging
to reach people in their everyday lives when self-management of the condition is
vital. This systematic review aimed to assess the effectiveness of short message
service-based diabetes self-management interventions on glycaemic control in
adults with poorly controlled diabetes. Methods/design: MEDLINE, PubMed, EMBASE,
The Cochrane Library and PsychINFO were searched from inception through to 23
January 2017 for randomised controlled trials investigating the use of text
messaging based self-management interventions on haemoglobin A1c for patients
with poorly controlled diabetes. Results: Seven studies met the inclusion
criteria and were included in the review. Three of the studies reported a
significant decrease in haemoglobin A1c from baseline to follow-up in the
intervention group compared to the control group. No clear relationship between
positive outcomes and intervention dose, content and functionality was seen.
Discussion: Evidence supporting text messaging for improvements in glycaemic
control in people with poorly controlled diabetes is mixed. Previous reviews have
reported positive impacts on glycaemic control for short message service
interventions in patients with diabetes; however, when limited to those with
poorly controlled diabetes the evidence is less clear. Large-scale studies with
robust methodology and longer-term follow-up are needed to further understand the
impact of text-messaging-based self-management interventions for people with
poorly controlled diabetes.
PMID- 29942621
TI - The accuracy and promise of personal breathalysers for research: Steps toward a
cost-effective reliable measure of alcohol intoxication?
AB - Objective: Technology is continuing to shape the way we collect health data,
including data on alcohol use. A number of technologies are being developed to
objectively measure intoxication 'in the wild' without relying on self-report;
the most immediate solution may be the use of personal breathalysers. In this
study, we aimed to determine whether a cost-effective personal breathalyser would
perform in a similar manner to a device used for roadside breath testing. Method:
We intercepted young adults (n = 337; 45% men) outside three concerts,
administered 5-min interviews, and asked for breath samples on two devices (a
personal breathalyser and a police-grade breathalyser). Results: Participants
reported having consumed an average of 7.3 standard drinks before the interview
and had a mean Blood Alcohol Content of 0.077 g/dl on the police-grade device and
0.085 g/dl on the personal device. Difference scores suggested the personal
breathalyser was more likely to over report Blood Alcohol Content (bias = 0.008
g/dl). Conclusion: Although the personal device was more likely to over report
Blood Alcohol Content compared with the police-grade device, the results suggest
that personal devices could be used as a measure of Blood Alcohol Content when
collecting data outside of the lab.
PMID- 29942622
TI - What makes online substance-use interventions engaging? A systematic review and
narrative synthesis.
AB - Background: Online substance-use interventions are effective in producing
reductions in harmful-use. However, low user engagement rates with online
interventions reduces overall effectiveness of interventions. Identifying optimal
strategies with which to engage users with online substance-use interventions may
improve usage rates and subsequent effectiveness. Objectives: (1) To identify the
most prevalent engagement promoting strategies utilised to increase use of online
substance-use interventions. (2) To determine whether the identified engagement
promoting strategies increased said use of online substance-use interventions.
Review methods: The reviewed followed Cochrane methodology. Databases were
searched for online substance-use interventions and engagement promoting
strategies limited by study type (randomised controlled trial). Due to
heterogeneity between engagement promoting strategies and engagement outcomes,
meta-analytic techniques were not possible. Narrative synthesis methods were
used. Results: Fifteen studies were included. Five different engagement promoting
strategies were identified: (1) tailoring; (2) delivery strategies; (3)
incentives; (4) reminders; (5) social support. The most frequently reported
engagement promoting strategies was tailoring (47% of studies), followed by
reminders and social support (40% of studies) and delivery strategies (33% of
studies). The narrative synthesis demonstrated that tailoring, multimedia
delivery of content and reminders are potential techniques for promoting
engagement. The evidence for social support was inconclusive and negative for
incentives. Conclusions: This review was the first to examine engagement
promoting strategies in solely online substance-use interventions. Three
strategies were identified that may be integral in promoting engagement with
online substance-use interventions. However, the small number of eligible
extracted studies, inconsistent reporting of engagement outcomes and diversity of
engagement features prevent firmer conclusions. More high-quality trials
examining engagement are required.
PMID- 29942623
TI - Making the most of the waiting room: Electronic patient engagement, a mixed
methods study.
AB - Objective: The purpose of this study was to explore whether patients with
musculoskeletal conditions would agree to use digital technologies to learn about
research registries and make a decision about signing up whilst in the clinic
waiting room. Methods: Patients were recruited from four hospital clinics across
Oxfordshire. We used an explanatory mixed methods design with two sequential
phases comprising an exploratory, cross-sectional questionnaire (n = 84),
followed by focus group interviews (n = 8) to provide context for the findings
from the questionnaire. Multivariate ordinal logistic regression models were used
to explore relationships between patient preferences and characteristics.
Thematic analysis was used to understand the reasons for patient preferences
regarding digital technologies and research registries. Results: As participants'
age increased, they were more likely to report a preference for face-to-face
recruitment methods compared to those using digital technologies. Findings from
the focus groups indicated this was primarily due to a fear of technology and
physical limitations associated with a patient's condition. Patients also
reported a preference for making a decision about signing up at a later date,
which was attributed to patients feeling distracted whilst in the waiting room
due to anxieties related to their upcoming appointment. Conclusions: Many
patients with musculoskeletal conditions in the UK may be interested in learning
about opportunities to participate in research whilst using digital technologies
within the waiting room. The results suggest the need for choice regarding the
presentation and format of information and whether it can be accessed at a later
date at home.
PMID- 29942624
TI - Digital transformation in government: Lessons for digital health?
PMID- 29942626
TI - Effectiveness and impact of networked communication interventions in young people
with mental health conditions: A rapid review.
AB - Objective: To describe the latest evidence of effectiveness and impact of
networked communication interventions for young people with mental health
conditions. Methods: Searching five databases from 2009 onwards, we included
studies of any design investigating two-way communication interventions for the
treatment of young people (mean age 12-25) with a chronic mental health disorder.
The data were synthesised using narrative summary. Results: Six studies met the
inclusion criteria, covering a range of mental health conditions (depression,
psychosis, OCD). Interventions included an online chat room (n = 2),
videoconferencing (n = 3) and telephone (n = 1). Where studies compared two
groups, equivalence or a statistically significant improvement in symptoms was
observed compared to control. Views of patients and clinicians included impact on
the patient-clinician interaction. Clinicians did not feel it hindered their
diagnostic ability. Conclusion: Networked communication technologies show promise
in the treatment of young people with mental health problems but the current
available evidence remains limited and the evidence base has not advanced much
since the previous inception of this review in 2011. Practice implications:
Although the available research is generally positive, robust evidence relating
to the provision of care for young persons via these technologies is lacking and
healthcare providers should be mindful of this.
PMID- 29942627
TI - Investing in college students: the role of the fitness tracker.
AB - Fitness trackers are becoming a popular way to encourage physical activity and
impact health behaviors. Although many college students may own and use fitness
trackers, they remain a high-risk group in terms of rates of obesity and lack of
physical activity. In this study, college students were provided with fitness
trackers to self-monitor step count. Pre- and post-measures of body composition,
resting heart rate and blood pressure, knowledge of physical activity behaviors
and perception of wellness were used to determine the impact of the fitness
trackers. The research was completed in two phases: phase one with completely
voluntary participation and phase two as a part of a required general education
wellness course. Results did not indicate a significant change in step count over
12 weeks nor did they show positive change in body measurements; however, there
were indicators of activity benefits. Knowledge and perception of wellness were
not positively impacted in the voluntary study; however, when the education
component was required, some increases in knowledge and perception of wellness
were shown in the general education course. Many lessons were learned in the
study that should be considered when planning future research with fitness
trackers in the college-age setting.
PMID- 29942628
TI - Validity of wrist-worn consumer products to measure heart rate and energy
expenditure.
AB - Introduction: The ability to monitor physical activity throughout the day and
during various activities continues to improve with the development of wrist-worn
monitors. However, the accuracy of wrist-worn monitors to measure both heart rate
and energy expenditure during physical activity is still unclear. The purpose of
this study was to determine the accuracy of several popular wrist-worn monitors
at measuring heart rate and energy expenditure. Methods: Participants wore the
TomTom Cardio, Microsoft Band and Fitbit Surge on randomly assigned locations on
each wrist. The maximum number of monitors per wrist was two. The criteria used
for heart rate and energy expenditure were a three-lead electrocardiogram and
indirect calorimetry using a metabolic cart. Participants exercised on a
treadmill at 3.2, 4.8, 6.4, 8 and 9.7 km/h for 3 minutes at each speed, with no
rest between speeds. Heart rate and energy expenditure were manually recorded
every minute throughout the protocol. Results: Mean absolute percentage error for
heart rate varied from 2.17 to 8.06% for the Fitbit Surge, from 1.01 to 7.49% for
the TomTom Cardio and from 1.31 to 7.37% for the Microsoft Band. The mean
absolute percentage error for energy expenditure varied from 25.4 to 61.8% for
the Fitbit Surge, from 0.4 to 26.6% for the TomTom Cardio and from 1.8 to 9.4%
for the Microsoft Band. Conclusion: Data from these devices may be useful in
obtaining an estimate of heart rate for everyday activities and general exercise,
but energy expenditure from these devices may be significantly over- or
underestimated.
PMID- 29942629
TI - Seven lessons for interdisciplinary research on interactive digital health
interventions.
AB - Research and development for interactive digital health interventions requires
multi-disciplinary expertise in identifying user needs, and developing and
evaluating each intervention. Two of the central areas of expertise required are
Health (broadly defined) and Human-Computer Interaction. Although these share
some research methods and values, they traditionally have deep differences that
can catch people unawares, and make interdisciplinary collaborations challenging,
resulting in sub-optimal project outcomes. The most widely discussed is the
contrast between formative evaluation (emphasised in Human-Computer Interaction)
and summative evaluation (emphasised in Health research). However, the
differences extend well beyond this, from the nature of accepted evidence to the
culture of reporting. In this paper, we present and discuss seven lessons that we
have learned about the contrasting cultures, values, assumptions and practices of
Health and Human-Computer Interaction. The lessons are structured according to a
research lifecycle, from establishing the state of the art for a given digital
intervention, moving through the various (iterative) stages of development,
evaluation and deployment, through to reporting research results. Although our
focus is on enabling people from different disciplinary backgrounds to work
together with better mutual understanding, we also highlight ways in which future
research in this interdisciplinary space could be better supported.
PMID- 29942630
TI - Health literacy and digital media use: Assessing the Health Literacy Skills
Instrument - Short Form and its correlates among African American college
students.
AB - Improving health literacy is increasingly seen as a solution to health problems
and inequalities. This study assesses how one of the more recent measures of
health literacy, the Health Literacy Skills Instrument - Short Form, performs
among African American college students, and ascertains if and how media use
relates to health literacy. Results indicate that both the use of health-related
websites and apps as well as overall time spent with the media were positively,
but conditionally, linked to health literacy. However, findings also pointed to
the need for further test development.
PMID- 29942631
TI - The impact of digital health interventions on health-related outcomes in the
workplace: A systematic review.
AB - Background: The impact of employee health on productivity in the workplace is
generally evidenced through absenteeism and presenteeism. Multicomponent worksite
health programmes, with significant online elements, have gained in popularity
over the last two decades, due in part to their scalability and low cost of
implementation. However, little is known about the impact of digital-only
interventions on health-related outcomes in employee groups. The aim of this
systematic review was to assess the impact of pure digital health interventions
in the workplace on health-related outcomes. Methods: Multiple databases,
including MEDLINE, EMBASE, PubMed and PsycINFO, were used to review the
literature using PRISMA guidelines. Results: Of 1345 records screened, 22
randomized controlled trial studies were found to be eligible. Although there was
a high level of heterogeneity across these studies, significant improvements were
found for a broad range of outcomes such as sleep, mental health, sedentary
behaviours and physical activity levels. Standardized measures were not always
used to quantify intervention impact. All but one study resulted in at least one
significantly improved health-related outcome, but attrition rates ranged widely,
suggesting sustaining engagement was an issue. Risk of bias assessment was low
for one-third of the studies and unclear for the remaining ones. Conclusions:
This review found modest evidence that digital-only interventions have a positive
impact on health-related outcomes in the workplace. High heterogeneity impacted
the ability to confirm what interventions might work best for which health
outcomes, although less complex health outcomes appeared to be more likely to be
impacted. A focus on engagement along with the use of standardized measures and
reporting of active intervention components would be helpful in future
evaluations.
PMID- 29942632
TI - Digital health technologies to support access to medicines and pharmaceutical
services in the achievement of sustainable development goals.
AB - Objectives: The objective of this study was to describe the conceptual and
implementation approach of selected digital health technologies that were
tailored in various resource-constrained countries. To provide insights from a
donor-funded project implementer perspective on the practical aspects based on
local context and recommendations on future directions. Methods: Drawing from our
multi-year institutional experience in more than 20 high disease-burden countries
that aspire to meet the 2030 United Nations Sustainable Development Goal 3, we
screened internal project documentation on various digital health tools that
provide clarity in the conceptual and implementation approach. Taking into
account geographic diversity, we provide a descriptive review of five selected
case studies from Bangladesh (Asia), Mali (Francophone Africa), Uganda (East
Africa), Mozambique (Lusophone Africa), and Namibia (Southern Africa). Findings:
A key lesson learned is to harness and build on existing governance structures.
The use of data for decision-making at all levels needs to be cultivated and
sustained through multi-stakeholder partnerships. The next phase of information
management development is to build systems for triangulation of data from
patients, commodities, geomapping, and other parameters of the pharmaceutical
system. A well-defined research agenda must be developed to determine the
effectiveness of the country- and regional-level dashboards as an early warning
system to mitigate stock-outs and wastage of medicines and commodities.
Conclusion: The level of engagement with users and stakeholders was resource
intensive and required an iterative process to ensure successful implementation.
Ensuring user acceptance, ownership, and a culture of data use for decision
making takes time and effort to build human resource capacity. For future United
Nations voluntary national reviews, countries and global stakeholders must
establish appropriate measurement frameworks to enable the compilation of
disaggregated data on Sustainable Development Goal 3 indicators as a precondition
to fully realize the potential of digital health technologies.
PMID- 29942633
TI - The use of social media among health professionals to facilitate chronic disease
self-management with their patients: A systematic review.
AB - Objective: The objective of this systematic review was to summarize the evidence
pertaining to the use of social media by health professionals to facilitate
chronic disease self-management with their patients. Methods: A systematic
approach was used to retrieve and extract relevant data. A total of 5163
citations were identified, of which seven unique studies met criteria for
inclusion; one was a randomized controlled trial, two were prospective cohort
studies, and four were qualitative studies. The following social media platforms
were evaluated: discussion forums (6 studies) and collaborative project (1
study). Results: The available evidence suggests that health professionals
perceived discussion forums and collaborative projects to be useful social media
platforms to facilitate chronic disease self-management with patients. No
relevant evidence was found regarding the use of other social media platforms.
Most studies indicated positive findings regarding health professionals'
intention to use discussion forums, while the one study that used a collaborative
project also indicated positive findings with its perceived ease of use as health
professionals felt that it was useful to facilitate chronic disease self
management with patients. Mixed findings were seen in regards to health
professionals' perceived ease of use of discussion forums. The most common
barrier to using social media platforms was the lack of time in health
professionals' schedules. Conclusions: Discussion forums and collaborative
projects appear to be promising resources for health professionals to assist
their patients in self-managing their chronic conditions; however, further
research comparing various social media platforms is needed.
PMID- 29942634
TI - Using social media for health research: Methodological and ethical considerations
for recruitment and intervention delivery.
AB - As the popularity and diversity of social media platforms increases so does their
utility for health research. Using social media for recruitment into clinical
studies and/or delivering health behavior interventions may increase reach to a
broader audience. However, evidence supporting the efficacy of these approaches
is limited, and key questions remain with respect to optimal benchmarks,
intervention development and methodology, participant engagement, informed
consent, privacy, and data management. Little methodological guidance is
available to researchers interested in using social media for health research. In
this Tutorial, we summarize the content of the 2017 Society for Behavioral
Medicine Pre-Conference Course entitled 'Using Social Media for Research,' at
which the authors presented their experiences with methodological and ethical
issues relating to social media-enabled research recruitment and intervention
delivery. We identify common pitfalls and provide recommendations for recruitment
and intervention via social media. We also discuss the ethical and responsible
conduct of research using social media for each of these purposes.
PMID- 29942635
TI - Seeking virtual social support through blogging: A content analysis of published
blog posts written by people with chronic pain.
AB - Objective: People with chronic pain often have limited avenues for social
support. Social isolation often develops as their abilities to engage in daily
social and vocational activities decrease. With recent advancements in technology
and increasing use of social media, virtual platforms such as blogging may
provide opportunities for social support. This study analyzed published blog
posts of people with chronic pain to investigate how social support occurs
through blogging for chronic pain blog users and the nature of such online
interactions. Methods: A total of 810 blog posts published from January 2014 to
December 2015 on 44 publicly accessible chronic pain blogs were collected and
analyzed through qualitative phenomenological thematic analysis. Results: The
Virtual Online Support Sequence (VOSS) was identified through the exchange of
online comments; this sequence defines the process by which virtual social
support can be established through the process of chronic pain blogging. Three
subthemes were also identified in relation to social support in the online
blogging environment: (a) the virtual community of pain blogging; (b)
establishing social support through the VOSS; and (c) recounting everyday
experiences related to pain. Conclusions: These findings suggest that blogging
can be useful in seeking, receiving and providing social support for people with
chronic pain. Understanding this mechanism behind establishing virtual social
support may potentially encourage people with chronic pain to pursue additional
support online if they have limited face-to-face opportunities.
PMID- 29942636
TI - Contradictions in digital health engagement: An activity tracker's ambiguous
influence on vulnerable young adults' engagement in own health.
AB - Objective: Activity trackers are designed to support individuals in monitoring
and increasing their physical activity. The use of activity trackers among
individuals diagnosed with depression and anxiety has not yet been examined. This
pilot study investigates how this target group engages with an activity tracker
during a 10-week health intervention aimed to increase their physical activity
level and improve their physical and mental health. Methods: Two groups of 11
young adults (aged 18-29 years) diagnosed with depression or anxiety participated
in the digital health intervention. The study used mixed methods to investigate
the research question. Quantitative health data were used to assess the
intervention's influence on the participants' health and qualitative data
provided insights into the participants' digital health experience. Results: The
study demonstrated an ambiguous influence from the use of an activity tracker
with positive physical and mental health results, but a fading and even negative
digital health engagement and counterproductive competition. Conclusions: The
ambiguous results identify a need for (1) developing strategies for health
professionals to provide supervised use of activity trackers and support the
target groups' abilities to convert health information about physical activity
into positive health strategies, and (2) designing alternatives for health
promoting IT targeted users who face challenges and need motivation beyond self
tracking and competition.
PMID- 29942637
TI - Apps and wearables for monitoring physical activity and sedentary behaviour: A
qualitative systematic review protocol on barriers and facilitators.
AB - Objective: Monitoring of physical activity and sedentary behaviours by mobile
phone applications (apps) and wearable technology (wearables) may improve these
health behaviours. This systematic review aims to synthesise the qualitative
literature on the barriers and facilitators of using apps and wearables for
monitoring physical activity and/or sedentary behaviour in adults. Methods: This
review protocol is registered in PROSPERO (CRD42017070194). Scientific databases
including CINAHL Complete, MEDLINE, PsycINFO, SPORTDiscus, Cochrane Library and
Scopus will be searched for relevant studies published from 1 January 2012 to the
date the searches are conducted. Studies will be included if they incorporated
adults who used an app or wearable for monitoring physical activity and/or
sedentary behaviour; explored the barriers and/or facilitators of using an app
and/or wearable; and were published in English. Following duplicate screening of
titles and abstracts, full texts of potentially eligible papers will be screened
to identify studies using qualitative approaches to explore barriers and
facilitators of using apps and/or wearables for monitoring physical activity
and/or sedentary behaviour. Discrepancies will be resolved through consensus or
by consulting a third screener. Relevant excerpts (quotes and text) from the
included papers will be extracted and analysed thematically. The Critical
Appraisal Skills Programme Qualitative Research Checklist will be used to
appraise included studies. Conclusion: The results of this work will be useful
for those intending to monitor physical activity and/or sedentary behaviour using
these technologies.
PMID- 29942638
TI - Utilization of online focus groups to include mothers: A use-case design,
reflection, and recommendations.
AB - Advances in technology over the past decade have allowed unique methodologies to
emerge, enabling the engagement of hard-to-reach populations on sensitive topics
in a way that was before thought not possible with traditional face-to-face
modalities. This study aimed to use online focus group discussions (FGDs) to
explore breastfeeding mothers' use of social media. Results indicate participants
had a positive experience with online FGDs, and almost all preferred this method
to traditional face-to-face focus groups. We discuss reflections of the online
FGD experience, including best practices and recommendations for innovative ways
to include time-constrained or hard-to-reach participants, for yielding rich
qualitative data.
PMID- 29942639
TI - Comparison and transformation between CDISC ODM and EN13606 EHR standards in
connecting EHR data with clinical trial research data.
AB - Objectives: Integrating Electronic Health Record (EHR) systems into the field of
clinical trials still contains several challenges and obstacles. Heterogeneous
standards and specifications are used to represent healthcare and clinical trial
information. Therefore, this work investigates the mapping and data
interoperability between healthcare and research standards: EN13606 used for the
EHRs and the Clinical Data Interchange Standards Consortium Operational Data
Model (CDISC ODM) used for clinical research. Methods: Based on the
specifications of CDISC ODM 1.3.2 and EN13606, a mapping between the structure
and components of both standards has been performed. Archetype Definition
Language (ADL) forms built with the EN13606 editor were transformed to ODM XML
and reviewed. As a proof of concept, clinical sample data has been transformed
into ODM and imported into an electronic data capture system. Reverse
transformation from ODM to ADL has also been performed and finally reviewed
concerning map-ability. Results: The mapping between EN13606 and CDISC ODM shows
the similarities and differences between the components and overall record
structure of the two standards. An EN13606 archetype corresponds with a group of
items within CDISC ODM. Transformations of element names, descriptions, different
languages, datatypes, cardinality, optionality, units, value range and
terminology codes are possible from EN13606 to CDISC ODM and vice versa.
Conclusion: It is feasible to map data elements between EN13606 and CDISC ODM and
transformation of forms between ADL and ODM XML format is possible with only
minor limitations. EN13606 can accommodate clinical information in a more
structured manner with more constraints, whereas CDISC ODM is more suitable and
specific for clinical trials and studies. It is feasible to transform EHR data in
the EN13606 form to ODM to transfer it into research database. The attempt to use
EN13606 to build a study protocol (that was already built with CDISC ODM) also
suggests the possibility of using EN13606 standard in place of CDISC ODM if
needed to avoid transformations.
PMID- 29942640
TI - Seeking connectivity to everyday health and wellness experiences: Specificities
and consequences of connective gaps in self-tracking data.
AB - Objective: Self-tracking technologies have created high hopes, even hype, for
aiding people to govern their own health risks and promote optimal wellness. High
expectations do not, however, necessarily materialize due to connective gaps
between personal experiences and self-tracking data. This study examines
situations when self-trackers face difficulties in engaging with, and reflecting
on, their data with the aim of identifying the specificities and consequences of
such connective gaps in self-tracking contexts. Methods: The study is based on
empirical analyses of interviews of inexperienced, experienced and extreme self
trackers (in total 27), who participated in a pilot study aiming at promoting
health and wellness. Results: The study shows that people using self-tracking
devices actively search for constant connectivity to their everyday experiences
and particularly health and wellness through personal data but often become
disappointed. The results suggest that in connective gaps the personal data
remains invisible or inaccurate, generating feelings of confusion and doubt in
the users of the self-tracking devices. These are alarming symptoms that may lead
to indifference when disconnectivity becomes solidified and data ends up becoming
dead, providing nothing useful for the users of self-tracking technologies.
Conclusions: High expectations which are put on wearables to advance health and
wellness may remain unmaterialised due to connective gaps. This is problematic if
individuals are increasingly expected to be active in personal data collection
and interpretation regarding their own health and wellness.
PMID- 29942641
TI - Challenges faced with the implementation of Web-Based Data Query Systems for
population health: development of a questionnaire based on expert consensus.
AB - Background: State health agencies (SHA) and local health agencies (LHA) face
several challenges with the dissemination of local health data using Web-Based
Data Query Systems (WDQS). To help guide future research, this study aimed to
utilize expert consensus to identify the most relevant items that contribute to
these challenges. Methods: A total of 17 researchers and public health
professionals agreed to participate in a three-round Delphi process. In round 1,
four topics were represented on a 42-item questionnaire using a 5-point Likert
scale, along with free-text responses. Free-text responses were analyzed leading
to a series of items for a second Delphi round. Participants were given an
opportunity to revise results in round 3 for items that did not meet consensus in
round 1 or round 2. Consensus on expert opinions was defined at interquartile
range (IQR) <= 1. Results: The experts reached consensus on a total of 21 (50%)
of the 42 items presented in the initial questionnaire. Eleven of the 15 (73%) of
the items extracted from the free-text responses met consensus. Items in
consensus from this pilot study were used to develop an instrument for a broader
survey across Behavioral Risk Factor Surveillance System (BRFSS) coordinators
across all 50 US states. Conclusion: Experts confirmed that software development
costs, inadequate human resources, data sharing gaps, a lack of political
support, and poor data quality contribute significantly to challenges in their
data implementation. The findings from this pilot study inform us of items of
public health significance that will help guide future research.
PMID- 29942642
TI - Synthesis of a gadolinium based-macrocyclic MRI contrast agent for effective
cancer diagnosis.
AB - Background: Gadolinium-based contrast agents are widely used as a contrast agent
for magnetic resonance imaging. Since gadolinium ions are toxic, many chelators
are developed to bind gadolinium ions to prevent free gadolinium-associated
disease. However, many reports indicated that linear chelator-based contrast
agents are associated with nephrogenic systemic fibrosis (NSF) in patients with
low kidney function. Therefore, the demand for stable macrocyclic chelator-based
contrast agent is now increasing. Method: 1,4,7,10-Tetraazacyclododecane-1,4,7,10
tetraacetate (DOTA) was conjugated to lactobionic acid (LBA) through DCC-NHS
coupling reaction. Gd3+ (gadolinium ion) was chelated to 1,4,7,10
Tetraazacyclododecane-1,4,7,10-tetraacetate-lactobionic acid (DOTA-LAE) and free
Gd3+ was removed using a cation exchange column. In vitro cytotoxicity of
contrast agent towards normal cells was measured using MTT assay. For in vivo MR
imaging, contrast agents were intravenously injected to tumor-bearing mice and
imaged by a MR imaging scanner. Results: This new macrocyclic gadolinium-based
contrast agent showed enhanced in vitro paramagnetic properties compared to
Gadovist. In addition, Gd-DOTA-LAE showed a 29% increased contrast enhancement of
tumor tissue compared to normal tissue within 20 min past IV injection.
Conclusions: We developed a new macrocyclic T1-weighted MR contrast agent. This
new contrast agent offers various opportunities for cancer detection and
diagnosis.
PMID- 29942643
TI - A comprehensive comparison of sex-inducing activity in asexual worms of the
planarian Dugesia ryukyuensis: the crucial sex-inducing substance appears to be
present in yolk glands in Tricladida.
AB - Background: Turbellarian species can post-embryonically produce germ line cells
from pluripotent stem cells called neoblasts, which enables some of them to
switch between an asexual and a sexual state in response to environmental
changes. Certain low-molecular-weight compounds contained in sexually mature
animals act as sex-inducing substances that trigger post-embryonic germ cell
development in asexual worms of the freshwater planarian Dugesia ryukyuensis
(Tricladida). These sex-inducing substances may provide clues to the molecular
mechanism of this reproductive switch. However, limited information about these
sex-inducing substances is available. Results: Our assay system based on feeding
sex-inducing substances to asexual worms of D. ryukyuensis is useful for
evaluating sex-inducing activity. We used the freshwater planarians D.
ryukyuensis and Bdellocephala brunnea (Tricladida), land planarian Bipalium
nobile (Tricladida), and marine flatworm Thysanozoon brocchii (Polycladida) as
sources of the sex-inducing substances. Using an assay system, we showed that the
three Tricladida species had sufficient sex-inducing activity to fully induce
hermaphroditic reproductive organs in asexual worms of D. ryukyuensis. However,
the sex-inducing activity of T. brocchii was sufficient only to induce a pair of
ovaries. We found that yolk glands, which are found in Tricladida but not
Polycladida, may contain the sex-inducing substance that can fully sexualize
asexual worms of D. ryukyuensis. Conclusions: Our results suggest that within
Tricladida, there are one or more common compounds or functional analogs capable
of fully sexualizing asexual worms of D. ryukyuensis; namely, the crucial sex
inducing substance (hydrophilic and heat-stable, but not a peptide) produced in
yolk glands.
PMID- 29942644
TI - Form and Function of the skin glands in the Himalayan newt Tylototriton
verrucosus.
AB - Background: Amphibians have evolved a remarkable diversity of defensive
mechanisms against predators. One of the most conspicuous components in their
defense is related to their ability to produce and store a high variety of
bioactive (noxious to poisonous) substances in specialized skin glands. Previous
studies have shown that T. verrucosus is poisonous with the potential to truly
harm or even kill would-be predators by the effect of its toxic skin secretions.
However, little is known on form and function of the skin glands responsible for
production and release of these secretions. Results: By using light- and scanning
electron microscopy along with confocal laser scanning microscopy, we show that
T. verrucosus exhibits three different multicellular skin glands: one mucous- and
two granular glands. While mucous glands are responsible for the production of
the slippery mucus, granular glands are considered the production site of toxins.
The first type of granular glands (GG1) is found throughout the skin, though its
average size can vary between body regions. The second type of granular glands
(GG2) can reach larger dimensions compared with the former type and is restricted
to the tail region. Despite their different morphology, all three skin gland
types are enwrapped by a distinct myoepithelial sheath that is more prominently
developed in the granular (i.e. poison-) glands compared to the mucous glands.
The myoepithelial sheath consists of one layer of regularly arranged slender
myoepithelial cells that run from the gland pore to the basal gland pole.
Conclusions: This study shows that the skin in the Himalayan newt T. verrucosus
displays one mucus- and two poison gland types enwrapped by a myoepithelial
sheath. Contraction of the myoepithelium squeezes the glands and glandular
content is released upon the skin surface where the secretion can deploy its
defensive potential.
PMID- 29942645
TI - Bapx1 upregulation is associated with ectopic mandibular cartilage development in
amphibians.
AB - Background: The emergence of novel structures during evolution is crucial for
creating variation among organisms, but the underlying processes which lead to
the emergence of evolutionary novelties are poorly understood. The gnathostome
jaw joint is such a novelty, and the incorporation of bapx1 expression into the
intermediate first pharyngeal arch may have played a major role in the evolution
of this joint. Knockdown experiments revealed that loss of bapx1 function leads
to the loss of the jaw joint, because Meckel's cartilage and the palatoquadrate
fuse during development. We used Xenopus laevis and Ambystoma mexicanum to
further investigate the function of bapx1 in amphibians. Bapx1 expression levels
were upregulated through the use of Ly-294,002 and we investigated the potential
consequences of the enhanced bapx1 expression in amphibians to test the
hypothesized joint inducing function of bapx1. Results: We show that Ly-294,002
upregulates bapx1 expression in vivo. Additionally, ectopic mandibular arch
derived cartilages develop after Ly-294,002 treatment. These ectopic cartilages
are dorsoventrally oriented rods situated lateral to the palatoquadrate. The
development of these additional cartilages did not change the muscular
arrangement of mandibular arch-derived muscles. Conclusions: Development of
additional mandibular cartilages is not unusual in larval anurans. Therefore,
changes in the bapx1 expression during evolution may have been the reason for the
development of several additional cartilages in the larval anuran jaw.
Furthermore, our observations imply a joint-promoting function of bapx1, which
further substantiates its hypothetical role in the evolution of the gnathostome
jaw joint.
PMID- 29942646
TI - Lactosylated N-Alkyl polyethylenimine coated iron oxide nanoparticles induced
autophagy in mouse dendritic cells.
AB - Dendritic cell (DC)-based vaccines have shown promising therapeutic results in
cancer and some immune disorders. It is critical to track in vivo migration
behaviours of DCs and monitor the whole process dynamically and non-invasively.
Superparamagnetic iron oxide (SPIO) nanoparticles are chosen for DC labelling
under magnetic resonance imaging (MRI) because of their proven biosafety as
contrast agents. However, when used for cell labelling, sensitive biological
indicators such as cell autophagy may be helpful to better understand the process
and improve the probe design. Here, lactosylated N-Alkyl polyethylenimine coated
SPIO nanoparticles are used for DC labelling. This probe shows satisfactory cell
labelling efficiency and low cytotoxicity. In this study, autophagy was used as a
key factor to understand how DCs react to nanoparticles after labelling. Our
results demonstrate that the nanoparticles can induce protective autophagy in
DCs, as inhibition of the autophagy flux could lead to cell death. Meanwhile, the
nanoparticles induced autophagy could promote DC maturation which is an essential
process for its migration and antigen presentation. Autophagy induced DC
maturation is known to enhance the vaccine functions of DCs, therefore, our
results suggest that beyond the MRI tracking ability, this probe might enhance
therapeutic immune activation as well.
PMID- 29942647
TI - A study of the initial adhesive force of cells on silk fibroin-based materials
using micropipette aspiration.
AB - With the development of biomaterials, more attention is paid to the adhesion
characteristics between cells and materials. It is necessary to study the
adhesive force with a suitable method. Silk fibroin (SF) is widely investigated
in biomedical application due to its novel biocompatibility and mechanical
properties. In this article, the micropipette aspiration method and measurement
pattern of uniform cells in round shape (UCR) was used to study the initial
adhesive force of three types of cells on pure silk fibroin films (SFFs). We also
compared the adhesive forces of modified SFFs with that of pure SFFs. The results
of adhesive force in the initial adhesive stage were in concordance with the
results of MTT assay and microscope observation, which were confirmed by the
above three cell lines and four kinds of SFFs. The results indicated UCR was an
efficient and quantitative measurement pattern in initial adhesion stage. This
article also provides a useful method in identifying initial cell-materials
interactions.
PMID- 29942649
TI - Poly (ethylene glycol) hydrogel elasticity influences human mesenchymal stem cell
behavior.
AB - Coordinated investigations into the interactions between biologically mimicking
(biomimetic) material constructs and stem cells advance the potential for the
regeneration and possible direct replacement of diseased cells and tissues. Any
clinically relevant therapies will require the development and optimization of
methods that mass produce fully functional cells and tissues. Despite advances in
the design and synthesis of biomaterial scaffolds, one of the biggest obstacles
facing tissue engineering is understanding how specific extracellular cues
produced by biomaterial scaffolds influence the proliferation and differentiation
of various cell sources. Matrix elasticity is one such tailorable property of
synthetic scaffolds that is known to differ between tissues. Here, we investigate
the interactions between an elastically tailorable polyethylene glycol (PEG)
based hydrogel platform and human bone marrow-derived mesenchymal stem cells
(hMSCs). For these studies, two different hydrogel compositions with elastic
moduli in the ranges of 50-60 kPa and 8-10 kPa were implemented. Our findings
demonstrate that the different elasticities in this platform can produce changes
in hMSC morphology and proliferation, indicating that the platform can be
implemented to produce changes in hMSC behavior and cell state for a broad range
of tissue engineering and regenerative applications. Furthermore, we show that
the platform's different elasticities influence stem cell differentiation
potential, particularly when promoting stem cell differentiation toward cell
types from tissues with stiffer elasticity. These findings add to the evolving
and expanding library of information on stem cell-biomaterial interactions and
opens the door for continued exploration into PEG-based hydrogel scaffolds for
tissue engineering and regenerative medicine applications.
PMID- 29942648
TI - Synthesis of photo-reactive poly (vinyl alcohol) and construction of scaffold
free cartilage like pellets in vitro.
AB - Photo-reactive poly(vinyl alcohol) (PRPVA) was synthesized by introduction of
phenyl azido groups into poly(vinyl alcohol) (PVA) and applied for surface
modification. PRPVA was grafted onto cell culture plate surface homogeneously or
in a micropattern. Human mesenchymal stem cells (hMSCs) cultured on cell culture
plate surface and PVA-modified surface showed different behaviors. Cells adhered
and spread well on cell culture plate surface, while they did not adhere on PVA
grafted surface at all. When hMSCs were cultured on PVA-micropatterned surface,
they formed a cell micropattern. Cells formed pellets after cultured on PVA
homogeneously modified surface in chondrogenic induction medium for 2 weeks. The
pellets were positively stained by hematoxylin/eosin, safranin-O/fast green and
toluidin blue, and they were also stained brown by Type II collagen and
proteoglycan immunohistological staining. Real-time PCR analysis was conducted to
investigate the expression of colI, colII, colX, aggrecan and sox9 mRNA. Results
of gene expression were in agreement with those of histological and
immunohistological observations. These results indicated that hMSCs cultured on
PVA-modified surface performed chondrogenic differentiation, and it was possible
to construct scaffold-free cartilage like pellets with PVA-modified surface in
vitro.
PMID- 29942651
TI - Gamma Knife radiosurgery for locally recurrent choroidal melanoma following
plaque radiotherapy.
AB - Background: For the majority of eyes with choroidal melanoma, radiation therapy
is the treatment of choice. Local recurrence after radiation therapy can occur,
however, and when it does, salvaging the globe with useful vision is atypical.
Case presentation: We report a case of late, local failure 7 years following
previous brachytherapy successfully managed with Gamma Knife radiosurgery (GKR).
With 3 years of follow up after GKR, the visual acuity is 20/20 and there is no
evidence of systemic metastases. Conclusion: To our knowledge, this is the first
report of successful salvage GKR therapy after brachytherapy failure in an eye
with choroidal melanoma. GKR is an option for select cases of local recurrence
after radiation plaque brachytherapy.
PMID- 29942650
TI - Endovascular stent-induced alterations in host artery mechanical environments and
their roles in stent restenosis and late thrombosis.
AB - Cardiovascular stent restenosis remains a major challenge in interventional
treatment of cardiovascular occlusive disease. Although the changes in arterial
mechanical environment due to stent implantation are the main causes of the
initiation of restenosis and thrombosis, the mechanisms that cause this
initiation are still not fully understood. In this article, we reviewed the
studies on the issue of stent-induced alterations in arterial mechanical
environment and discussed their roles in stent restenosis and late thrombosis
from three aspects: (i) the interaction of the stent with host blood vessel,
involve the response of vascular wall, the mechanism of mechanical signal
transmission, the process of re-endothelialization and late thrombosis; (ii) the
changes of hemodynamics in the lumen of the vascular segment and (iii) the
changes of mechanical microenvironment within the vascular segment wall due to
stent implantation. This review has summarized and analyzed current work in order
to better solve the two main problems after stent implantation, namely in stent
restenosis and late thrombosis, meanwhile propose the deficiencies of current
work for future reference.
PMID- 29942652
TI - The substitution rate of HIV-1 subtypes: a genomic approach.
AB - HIV-1M causes most infections in the AIDS pandemic. Its genetic diversity is
defined by nine pure subtypes and more than sixty recombinant forms. We have
performed a comparative analysis of the evolutionary rate of five pure subtypes
(A1, B, C, D, and G) and two circulating recombinant forms (CRF01_AE and CRF02
AG) using data obtained from nearly complete genome coding sequences. Times to
the most recent common ancestor (tMRCA) and substitution rates of these HIV
genomes, and their genomic partitions, were estimated by Bayesian coalescent
analyses. Genomic substitution rate estimates were compared between the HIV-1
datasets analyzed by means of randomization tests. Significant differences in the
rate of evolution were found between subtypes, with subtypes C and A1 and
CRF01_AE displaying the highest rates. On the other hand, CRF02_AG and subtype D
were the slowest evolving types. Using a different molecular clock model for each
genomic partition led to more precise tMRCA estimates than when linking the same
clock along the HIV genome. Overall, the earliest tMRCA corresponded to subtype
A1 (median = 1941, 95% HPD = 1943-55), whereas the most recent tMRCA corresponded
to subtype G and CRF01_AE subset 3 (median = 1971, 95% HPD = 1967-75 and median =
1972, 95% HPD = 1970-75, respectively). These results suggest that both
biological and epidemiological differences among HIV-1M subtypes are reflected in
their evolutionary dynamics. The estimates obtained for tMRCAs and substitution
rates provide information that can be used as prior distributions in future
Bayesian coalescent analyses of specific HIV-1 subtypes/CRFs and genes.
PMID- 29942653
TI - Chikungunya virus evolution following a large 3'UTR deletion results in host
specific molecular changes in protein-coding regions.
AB - The 3'untranslated region (UTR) in alphavirus genomes functions in virus
replication and plays a role in determining virus host range. However, the
molecular evolution of virus UTRs is understudied compared to the evolution of
protein-coding regions. Chikungunya virus (CHIKV) has the longest 3'UTR among the
alphaviruses (500-700 nt), and 3'UTR length and sequence structure vary
substantially among different CHIKV lineages. Previous studies showed that
genomic deletions and insertions are key drivers of CHIKV 3'UTR evolution.
Inspired by hypothesized deletion events in the evolutionary history of CHIKV, we
used experimental evolution to examine CHIKV adaptation in response to a large
3'UTR deletion. We engineered a CHIKV mutant with a 258 nt deletion in the 3'UTR
(DeltaDR1/2). This deletion reduced viral replication on mosquito cells, but did
not reduce replication on mammalian cells. To examine how selective pressures
from vertebrate and invertebrate hosts shape CHIKV evolution after a deletion in
the 3'UTR, we passaged DeltaDR1/2 virus populations strictly on primate cells,
strictly on mosquito cells, or with alternating primate/mosquito cell passages.
We found that virus populations passaged on a single host cell line increased in
fitness relative to the ancestral deletion mutant on their selected host, and
viruses that were alternately passaged improved on both hosts. Surprisingly,
whole genome sequencing revealed few changes in the 3'UTR of passaged
populations. Rather, virus populations evolved improved fitness through mutations
in protein coding regions that were associated with specific hosts.
PMID- 29942655
TI - Patterns of genomic site inheritance in HIV-1M inter-subtype recombinants
delineate the most likely genomic sites of subtype-specific adaptation.
AB - Recombination between different HIV-1 group M (HIV-1M) subtypes is a major
contributor to the ongoing genetic diversification of HIV-1M. However, it remains
unclear whether the different genome regions of recombinants are randomly
inherited from the different subtypes. To elucidate this, we analysed the
distribution within 82 circulating and 201 unique recombinant forms (CRFs/URFs),
of genome fragments derived from HIV-1M Subtypes A, B, C, D, F, and G and
CRF01_AE. We found that viruses belonging to the analysed HIV-1M subtypes and
CRF01_AE contributed certain genome fragments more frequently during
recombination than other fragments. Furthermore, we identified statistically
significant hot-spots of Subtype A sequence inheritance in genomic regions
encoding portions of Gag and Nef, Subtype B in Pol, Tat and Env, Subtype C in
Vif, Subtype D in Pol and Env, Subtype F in Gag, Subtype G in Vpu-Env and Nef,
and CRF01_AE inheritance in Vpu and Env. The apparent non-randomness in the
frequencies with which different subtypes have contributed specific genome
regions to known HIV-1M recombinants is consistent with selection strongly
impacting the survival of inter-subtype recombinants. We propose that hotspots of
genomic region inheritance are likely to demarcate the locations of subtype
specific adaptive genetic variations.
PMID- 29942656
TI - Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10.
AB - The Bayesian Evolutionary Analysis by Sampling Trees (BEAST) software package has
become a primary tool for Bayesian phylogenetic and phylodynamic inference from
genetic sequence data. BEAST unifies molecular phylogenetic reconstruction with
complex discrete and continuous trait evolution, divergence-time dating, and
coalescent demographic models in an efficient statistical inference engine using
Markov chain Monte Carlo integration. A convenient, cross-platform, graphical
user interface allows the flexible construction of complex evolutionary analyses.
PMID- 29942654
TI - Selective constraint and adaptive potential of West Nile virus within and among
naturally infected avian hosts and mosquito vectors.
AB - Arthropod-borne viruses are among the most genetically constrained RNA viruses,
yet they have a remarkable propensity to adapt and emerge. We studied wild birds
and mosquitoes naturally infected with West Nile virus (WNV) in a 'hot spot' of
virus transmission in Chicago, IL, USA. We generated full coding WNV genome
sequences from spatiotemporally matched bird and mosquito samples using high
throughput sequencing, allowing a molecular evolutionary assessment with deep
coverage. Mean FST among samples was 0.66 (+/-0.02 SE) and was bimodal, with mean
nucleotide diversity being higher between samples (interhost piN = 0.001; piS =
0.024) than within them (intrahost piN < 0.0001; piS < 0.001). Eight genomic
sites with FST > 1.01 (in the PrM, NS2a, NS3, NS4b, and 5'-noncoding genomic
regions) showed bird versus mosquito variant frequency differences of >30 per
cent and/or polymorphisms fixed in >=5 host or vector individuals, suggesting
host tropism for these variants. However, phylogenetic analyses demonstrated a
lack of grouping by bird or mosquito, most inter-sample differences were
synonymous (mean interhost piN/piS = 0.04), and there was no significant
difference between hosts and vectors in either their nucleotide diversities or
levels of purifying selection (mean intrahost piN/piS = 0.28 in birds and piN/piS
= 0.21 in mosquitoes). This finding contrasts with the 'trade-off' and 'selective
sieve' hypotheses that have been proposed and tested in the laboratory, which
predict strong host versus vector effects on WNV genetic variation, with
heightened selective constraint in birds alternating with heightened viral
diversity in mosquitoes. Overall, our data show WNV to be highly selectively
constrained within and between both hosts and vectors but still able to vary at a
limited number of sites across the genome. Such site-specific plasticity in the
face of overall selective constraint may offer a mechanism whereby highly
constrained viruses such as WNV and its relatives can still adapt and emerge.
PMID- 29942657
TI - Viral attenuation by engineered protein fragmentation.
AB - A possible but untested method of viral attenuation is protein fragmentation,
engineering wild-type proteins as two or more peptides that self-assemble after
translation. Here, the bacteriophage T7 was engineered to encode its essential
RNA polymerase as two peptides. Initial fitness was profoundly suppressed.
Subjecting the engineered virus to over 100 generations of adaptation by serial
transfer resulted in a large fitness increase, still remaining below that of
evolved wild-type. The fitness increase was accompanied by three substitutions in
the fragmented peptides as well as six mutations in other parts of the genome,
but the fragmentation was retained. This study thereby demonstrates the
feasibility of using gene fragmentation as a possibly permanent method of
attenuation, but the initial fitness of the engineered genome may be a poor
measure of its fitness on extended adaptation.
PMID- 29942658
TI - Adapting form to function: can simulation serve our healthcare system and
educational needs?
PMID- 29942659
TI - An empirical model for educational simulation of cervical dilation in first-stage
labor.
AB - Background: Several models for educational simulation of labor and delivery were
published in the literature and incorporated into a commercially available
training simulator (CAE Healthcare Lucina). However, the engine of this simulator
does not include a model for the clinically relevant indicators: uterine
contraction amplitude and frequency, and cervical dilation. In this paper, such a
model is presented for the primigravida in normal labor. Methods: The conceptual
and mathematical models represent oxytocin release by the hypothalamus, oxytocin
pharmacokinetics, and oxytocin effect on uterine contractions, cervical dilation,
and (positive) feedback from cervical dilation to oxytocin release by the
hypothalamus. Results: Simulation results for cervical dilation are presented,
together with target data for a normal primigravida. Corresponding oxytocin
concentrations and amplitude and frequency of uterine contractions are also
presented. Conclusion: An original empirical model for educational simulation of
oxytocin concentration, uterine contractions, and cervical dilation in first
stage labor is presented. Simulation results for cervical dilation match target
data for a normal patient. The model forms a basis for taking into account more
independent variables and patient profiles and can thereby considerably expand
the range of training scenarios that can be simulated.
PMID- 29942660
TI - A nanomedicine approach enables co-delivery of cyclosporin A and gefitinib to
potentiate the therapeutic efficacy in drug-resistant lung cancer.
AB - Drug resistance, accounting for therapeutic failure in the clinic, remains a
major challenge to effectively manage cancer. Cyclosporin A (CsA) can reverse
multidrug resistance (MDR), especially resistance to epidermal growth factor
receptor tyrosine kinase inhibitors. However, the application of both drugs in
cancer therapies is hampered by their poor aqueous solubility and low
bioavailability due to oral administration. CsA augments the potency of gefitinib
(Gef) in both Gef-sensitive and Gef-resistant cell lines. Here, we show that the
simultaneous encapsulation of CsA and Gef within polyethylene glycol-block
poly(D, L-lactic acid) (PEG-PLA) produced a stable and systemically injectable
nanomedicine, which exhibited a sub-50-nm diameter and spherical structures.
Impressively, the co-delivery of therapeutics via single nanoparticles (NPs)
outperformed the oral administration of the free drug combination at suppressing
tumor growth. Furthermore, in vivo results indicated that CsA formulated in NPs
sensitized Gef-resistant cells and Gef-resistant tumors to Gef treatment by
inactivating the STAT3/Bcl-2 signaling pathway. Collectively, our nanomedicine
approach not only provides an alternative administration route for the drugs of
choice but also effectively reverses MDR, facilitating the development of
effective therapeutic modalities for cancer.
PMID- 29942661
TI - Empirical antimicrobial treatment in haemato-/oncological patients with
neutropenic sepsis.
AB - Neutropenic sepsis in haemato-/oncological patients is a medical emergency, as
infections may show a fulminant clinical course. Early differentiation between
sepsis and febrile neutropenic response often proves to be challenging. To assess
the severity of the illness, different tools, which are discussed in this
article, are available. Once the diagnosis has been established, the correct use
of early empirical antibiotic and antifungal treatment is key in improving
patient survival. Therefore, profound knowledge of local resistance patterns is
mandatory and carefully designed antibiotic regimens have to be established in
cooperation with local microbiologists or infectious diseases specialists. In the
following, identification, therapy and management of high-risk, neutropenic
patients will be reviewed based on experimental and clinical studies, guidelines
and reviews.
PMID- 29942662
TI - 30 Immunotherapy in advanced NSCLC-from the 'tsunami' of therapeutic knowledge to
a clinical practice algorithm: results from an international expert panel meeting
of the Italian Association of Thoracic Oncology (AIOT).
AB - Although lung cancer remains the leading cause of death from cancer worldwide,
the advent of immunotherapy is changing the survival of patients affected by non
small cell lung cancer (NSCLC). A multitude of clinical trials are evaluating
different immune checkpoints inhibitors in this new field of thoracic oncology.
At the beginning of the immunotherapy era, nivolumab, pembrolizumab and
atezolizumab showed high efficacy in patients with advanced NSCLC in second-line
setting, receiving approvals for clinical practice. Nivolumab and atezolizumab
are approved independently from programmed death lig and 1 (PD-L1) expression,
while pembrolizumab is currently approved only for patients with PD-L1 expression
>=1%. The role of PD-L1 expression acquired more interest considering first-line
clinical trials, in which the role of immunotherapy as monotherapy was confirmed
only for pembrolizumab in patients with PD-L1 expression >=50%. These data were
analysed in this paper, focusing on the implications in clinical practice and how
to use them to an accurate clinical benefit of patients with advanced NSCLC. We
report a review based on a MEDLINE/PubMed, searched for randomised phase 2/3
trials evaluating immune checkpoint inhibitors and NSCLC, that moved to an
approval from Food and Drug Administration (FDA) and European Medicine Agency
(EMA). The evidence discussed in this manuscript and the final therapeutic
algorithm, coming out from an International Experts Panel Meeting of the Italian
Association of Thoracic Oncology.
PMID- 29942663
TI - Clonal evolution of colorectal cancer in a patient with serially resected
metastases and liquid biopsies: a case report and discussion of the literature.
AB - Background: Metastatic colorectal cancer represents a striking example of clonal
heterogeneity and tumour evolution, which generates acquired resistance to
therapy. Once hard to perform, the study of clonal heterogeneity is now
significantly aided by the use of liquid biopsies. Method: We herein report a
case of a patient with colorectal cancer and serial development of multiple
metastases which were all resected and genotyped. A rare point mutation was
identified in the primary tumour (but not in any of the organ metastatic sites),
as well as in the first and the last out of three consecutive liquid biopsies.
The review of the literature offered some insight in the evolution of the
patient's tumour and general directions on how to interpret liquid biopsy
results. Conclusions: This patient case emphasises the need for large prospective
studies designed to bridge liquid biopsy data with useful clinical endpoints, in
order to optimally integrate this revolutionary tool in everyday practice.
PMID- 29942665
TI - Role of chemotherapy in resectable liver metastases from colorectal cancer: food
for thought from pooled evidence.
PMID- 29942664
TI - Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2
negative metastatic breast cancer: a systematic review and meta-analysis.
AB - Single-agent poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been
approved as the first targeted therapy available for patients with BRCA-mutated
HER2-negative metastatic breast cancer. This meta-analysis aimed to better
evaluate activity, efficacy and safety of single-agent PARPi in this population.
A systematic search of Medline, Embase and conference proceedings up to 31
January 2018 was conducted to identify randomised controlled trials (RCTs)
investigating single-agent PARPi versus monochemotherapy in patients with BRCA
mutated HER2-negative metastatic breast cancer. Using the random-effect model, we
calculated summary risk estimates (pooled HR and OR with 95% CI) for progression
free survival (PFS), overall survival (OS), objective response rate (ORR), any
grade and grade 3-4 adverse events (AEs), treatment discontinuation rate and time
to deterioration in quality of life (QoL). Two RCTs (n=733) were included. As
compared with monochemotherapy, single-agent PARPi significantly improved PFS (HR
0.56(95% CI 0.45 to 0.70)) and ORR (OR 4.15 (95% CI 2.82 to 6.10)), with no
difference in OS (HR 0.82 (95% CI 0.64 to 1.05)). Single-agent PARPi
significantly increased risk of anaemia and any grade headache, but reduced risk
of neutropenia and any grade palmar-plantar erythrodysesthesia syndrome as
compared with monochemotherapy. No significant differences in other AEs and
treatment discontinuation rate were observed. Patients treated with PARPi
experienced a significant delayed time to QoL deterioration (HR 0.40 (95% CI 0.29
to 0.54)). Single-agent PARPi showed to be an effective, well tolerated and
useful treatment in maintaining QoL of patients with BRCA-mutated HER2-negative
metastatic breast cancer.
PMID- 29942666
TI - Phase Ib/II trial evaluating the safety, tolerability and immunological activity
of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined
with FOLFOX in patients with metastatic colorectal cancer.
AB - Background: 5-Fluorouracil plus irinotecan or oxaliplatin alone or in association
with target therapy are standard first-line therapy for metastatic colorectal
cancer (mCRC). Checkpoint inhibitors targeting PD-1/PD-L1 demonstrated efficacy
on mCRC with microsatellite instability but remain ineffective alone in
microsatellite stable tumour. 5-Fluorouracil and oxaliplatin were known to
present immunogenic properties. Durvalumab (D) is a human monoclonal antibody
(mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its
receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte
associated protein 4 (CTLA-4). This study is designed to evaluate whether the
addition of PD-L1 and CTLA-4 inhibition to oxaliplatin, fluorouracil and
leucovorin (FOLFOX) increases treatment efficacy. Methods: This phase II study
(ClinicalTrials.gov NCT03202758) will assess the efficacy and safety of
FOLFOX/D/T association in patients with mCRC (n=48). Good performance status
patients (Eastern Cooperative Oncology Group <2) with untreated, RAS mutational
status mCRC will be eligible. Prior adjuvant therapy is allowed provided
recurrence is >6 months postcompletion. There is a safety lead in nine patients
receiving FOLFOX/D/T. Assuming no safety concerns the study will go on to include
39 additional patients. Patients will receive folinic acid (400 mg/m2)/5
fluorouracil (400 mg/m2 as bolus followed by 2400 mg/m2 as a 46-hour
infusion)/oxaliplatin (85 mg/m2) every 14 days with D (750 mg) D1 every 14 days
and T (75 mg) D1 every 28 days. After six cycles of FOLFOX only D/T will continue
until disease progression, death, intolerable toxicity, or patient/investigator
decision to stop. Primary endpoint is safety and efficacy according to
progression-free survival (PFS); secondary endpoints include overall response
rate and quality of life. Hypothesis is that a PFS of 50% at 6 months is
insufficient and a PFS of 70.7% is expected (with alpha=10%, beta=10%). Blood,
plasma and tumour tissue will be collected and assessed for potential prognostic
and predictive biomarkers.
PMID- 29942667
TI - Shortening adjuvant chemotherapy in stage III colon cancer: are we ready for a
change?
PMID- 29942668
TI - In the literature: June 2018.
PMID- 29942669
TI - Incidence of cetuximab-related infusion reaction in head and neck cancer
patients: may we predict it?
PMID- 29942670
TI - Practical issues of biomarker-assisted targeted therapy in precision medicine and
immuno-oncology era.
AB - The concept of precision medicine is not new, as multiplex and very sensitive
methods, or next-generation sequencing and matched targeted cancer therapies,
have come to clinical practice. Substantial progress has been made from the
discovery to the development and clinical application of biomarkers and matched
targeted therapies. However, there still remain many challenges and issues to be
overcome in each step, from acquisition of tumour tissues through validation of
biomarkers to the final decision on targeted therapy. This review will briefly
touch on these issues, hoping to provide a better understanding and application
of targeted therapy in cancer treatment in the era of precision medicine and
immuno-oncology. It also helps to understand that the meaning or value of
biomarker(s) and matched targeted therapy changes along with expansion of
knowledge and advance of methodology, and constant efforts have to be made in
evaluating the meaning and clinical value during the development and after the
establishment of biomarkers or the approval of matched targeted therapies, which
might be more complicated by the advent of new therapeutic agents and new
diagnostic methods.
PMID- 29942671
TI - Developing the public health workforce: training and recognizing specialists in
public health from backgrounds other than medicine: experience in the UK.
AB - Background: There is increasing recognition that improving health and tackling
inequalities requires a strong public health workforce capable of delivering key
public health functions across systems. The World Health Organization in Europe
has identified securing the delivery of the Essential Public Health Operations
and strengthening public health capacities within this as a priority.It is
acknowledged that current public health capacities and arrangements of public
health services vary considerably across the World Health Organization in
European Region, and investment in multidisciplinary workforce with new skills is
essential if public health services are to be delivered. Case presentation: This
paper describes the current situation in the UK where there are nationally funded
multidisciplinary programmes for training senior public health specialists.
Uniquely, the UK provides public health registration for multidisciplinary as
well as medical public health specialists. Conclusion: The transition from a
predominantly medical to a multidisciplinary public health specialist workforce
over a relatively short timescale is unprecedented globally and was the product
of a sustained period of grass roots activism aligned with national policy
innovation. the UK experience might provide a model for other countries seeking
to develop public health specialist workforce capacity in line with the Essential
Public Health Operations.
PMID- 29942672
TI - Correction: Human anti-HIV IgM detection by the OraQuick ADVANCE(r) Rapid HIV 1/2
Antibody Test.
AB - [This corrects the article DOI: 10.7717/peerj.4430.].
PMID- 29942673
TI - Feeding ecology and sexual dimorphism in a speciose flower beetle clade
(Hopliini: Scarabaeidae).
AB - The relationship between feeding ecology and sexual dimorphism is examined in a
speciose South African monkey beetle clade. We test whether feeding and mating at
a fixed site (embedding guild) is associated with greater levels of sexual
dimorphism and possibly sexual selection than species using unpredictable feeding
resources (non-embedding guild). Sexual dimorphism was measured using a point
scoring system for hind leg and colour across the two feeding guilds for >50% of
the regional fauna. Quantification of hind leg dimorphism using a scoring system
and allometric scaling were used to identify traits subject to sexual selection.
Feeding guild had a significant effect on hind leg dimorphism, with embedders
having high and non-embedders low scores. The sessile and defendable distribution
of females on stable platform flowers may favour contests and associated hind leg
weaponry. In contrast, degree of colour dimorphism between the sexes was not
associated with any particular feeding guild, and may serve to reduce male
conflict and combat. Embedder males had high proportions (~76%) of species with
positive allometric slopes for almost all hind leg traits. For male non
embedders, only ~37% of species showed positive scaling relationships.
Phylogenetic data, in conjunction with behavioural data on the function of leg
weaponry and visual signalling among males is needed to better understand the
link between sexual dimorphism and sexual selection in the radiation of the
monkey beetles.
PMID- 29942674
TI - Ampelisca eschrichtii Kroyer, 1842 (Ampeliscidae) of the Sakhalin Shelf in the
Okhotsk Sea starve in summer and feast in winter.
AB - Background: Ampelisca eschrichtii Kroyer, 1842 of the Sakhalin Shelf of the
Okhotsk Sea, Far Eastern Russia, comprise the highest known biomass concentration
of any amphipod population in the world and are a critically important prey
source for western gray whales. Growth and reproduction in this population has
not been apparent in summer. However, they are not accessible for sampling in
winter to test a previous default conclusion that they grow and reproduce in
winter. Methods: We tested the default winter growth and reproduction hypothesis
by detailed comparisons of the brood and gonad development among 40 females and
14 males and brood sizes among females observed since 2002. Our test included six
predictions of reproductive synchrony that would be apparent from gonad and brood
morphology if active reproduction occurs in summer. Results: We found high
prevalences of undersized and damaged oocytes, undersized broods, a lack of
females brooding fully formed juveniles, atrophied ovaries, and males with mature
sperm but lacking fully developed secondary sex morphologies required for pelagic
mating. All of these conditions are consistent with trophic stress and
starvation. Discussion: These A. eschrichtii populations therefore appear to
starve in summer and to grow and reproduce in winter. The Offshore A. eschrichtii
populations occur in summer below water strata bearing high phytoplankton
biomasses. These populations are more likely to feed successfully in winter when
storms mix phytoplankton to their depths.
PMID- 29942675
TI - Cities may save some threatened species but not their ecological functions.
AB - Background: Urbanization is one of the main causes of biodiversity loss
worldwide. Wildlife responses to urbanization, however, are greatly variable and,
paradoxically, some threatened species may achieve much larger populations in
urban than in natural habitats. Urban conservation hotspots may therefore help
some species avoid regional or even global extinctions, but not conserve their
often overlooked ecological functions in the wild. We aim to draw attention to
this issue using two species of globally threatened parrots occurring in the
Dominican Republic: the Hispaniolan amazon (Amazona ventralis) and the
Hispaniolan parakeet (Psittacara chloropterus). Methods: We conducted a large
scale roadside survey in June 2017 across the country to estimate the relative
abundance of parrots in natural habitats, rural habitats, and cities. We combined
this with informal interviews with local people to collect information on past
and current human impacts on parrot populations. We also looked for foraging
parrots to assess their potential role as seed dispersers, an ecological function
that has been overlooked until very recently. Results: Relative abundances of
both parrot species were negligible in rural areas and very low in natural
habitats. They were generally between one and two orders of magnitude lower than
that of congeneric species inhabiting other Neotropical ecosystems. Relative
abundances were six times higher in cities than in natural habitats in the case
of the Hispaniolan parakeet and three times higher in the case of the Hispaniolan
amazon. People indicated hunting for a source food and to mitigate crop damage as
causes of parrot population declines, and a vigorous illegal trade for parrots
(131 individuals recorded, 75% of them poached very recently), mostly obtained
from protected areas where the last small wild populations remain. We observed
parrots foraging on 19 plant species from 11 families, dispersing the fruits of
14 species by carrying them in their beaks and consuming them in distant perching
trees. They discarded undamaged mature seeds, with the potential to germinate, in
99.5% of cases (n = 306), and minimum dispersal distances ranged from 8 to 155 m
(median = 37 m). Discussion: The loss of ecological functions provided by some
species when they disappear from natural habitats and only persist in cities may
have long-term, unexpected effects on ecosystems. Our example demonstrates how
two cities may soon be the last refuges for two endemic parrots if overharvesting
continues, in which case their overlooked role as seed dispersers would be
completely lost in nature. The functional extinction of these species could
strongly affect vegetation communities in an island environment where seed
dispersal species are naturally scarce. While conservation plans must include
urban populations of threatened species, greater efforts are needed to restore
their populations in natural habitats to conserve ecological functions.
PMID- 29942676
TI - GEsture: an online hand-drawing tool for gene expression pattern search.
AB - Gene expression profiling data provide useful information for the investigation
of biological function and process. However, identifying a specific expression
pattern from extensive time series gene expression data is not an easy task.
Clustering, a popular method, is often used to classify similar expression genes,
however, genes with a 'desirable' or 'user-defined' pattern cannot be efficiently
detected by clustering methods. To address these limitations, we developed an
online tool called GEsture. Users can draw, or graph a curve using a mouse
instead of inputting abstract parameters of clustering methods. GEsture explores
genes showing similar, opposite and time-delay expression patterns with a gene
expression curve as input from time series datasets. We presented three examples
that illustrate the capacity of GEsture in gene hunting while following users'
requirements. GEsture also provides visualization tools (such as expression
pattern figure, heat map and correlation network) to display the searching
results. The result outputs may provide useful information for researchers to
understand the targets, function and biological processes of the involved genes.
PMID- 29942677
TI - Biological nitrification inhibition by root exudates of native species, Hibiscus
splendens and Solanum echinatum.
AB - Australian native species grow competitively in nutrient limited environments,
particularly in nitrogen (N) limited soils; however, the mechanism that enables
this is poorly understood. Biological nitrification inhibition (BNI), which is
the release of root exudates into the plant rhizosphere to inhibit the
nitrification process, is a hypothesized adaptive mechanism for maximizing N
uptake. To date, few studies have investigated the temporal pattern and
components of root exudates by Australian native plant species for BNI. This
study examined root exudates from two Australian native species, Hibiscus
splendens and Solanum echinatum, and contrasted with exudates of Sorghum bicolor,
a plant widely demonstrated to exhibit BNI capacity. Root exudates were collected
from plants at two, four, and six weeks after transplanting to solution culture.
Root exudates contained three types of organic acids (OAs), oxalic, citric and
succinic acids, regardless of the species. However, the two Australian natives
species released larger amount of OAs in earlier development stages than S.
bicolor. The total quantity of these OAs released per unit root dry mass was also
seven-ten times greater for Australian native plant species compared to S.
bicolor. The root exudates significantly inhibited nitrification activity over
six weeks' growth in a potential nitrification assay, with S. echinatum (ca. 81%
inhibition) > S. bicolor (ca. 80% inhibition) > H. splendens (ca. 78%
inhibition). The narrow range of BNI capacity in the study plants limited the
determination of a relationship between OAs and BNI; however, a lack of
correlation between individual OAs and inhibition of nitrification suggests OAs
may not directly contribute to BNI. These results indicate that Australian native
species generate a strongly N conserving environment within the rhizosphere up to
six weeks after germination, establishing a competitive advantage in severely N
limited environments.
PMID- 29942678
TI - Comparative health assessment of urban and non-urban free-ranging mule deer
(Odocoileus hemionus) in southeastern British Columbia, Canada.
AB - Background: The provincial wildlife management agency, British Columbia Ministry
of Forests, Lands, Natural Resource Operations and Rural Development, performed a
translocation to control the urban mule deer (Odocoileus hemionus; uMD)
overpopulation and supplement the declining non-urban mule deer (nuMD) population
in the Kootenay region, British Columbia, Canada. The objectives of this cross
sectional study were to evaluate the health of the urban and nuMD populations by
comparing pathogen exposure, body condition scores (BCS) and pregnancy rates, to
characterize the health risks associated with the translocation and to
investigate the role of infectious diseases in the decline of the nuMD deer
population. Methods: Two hundred free-ranging mule deer were captured in urban
and non-urban environments in the Kootenay region from 2014 to 2017. BCS and
morphometric examinations were performed for each deer. Blood samples collected
from each deer were tested for exposure to selected pathogens and pregnancy
status. Results: Body condition scores averaged 3.4 on a five-point scale, was
greater in nuMD, and significantly differed between years. Antibodies were
detected for adenovirus hemorrhagic disease virus (38.4% (uMD 43.7%, nuMD
33.3%)), bluetongue virus (0.6% (uMD 1.2%, nuMD 0%)), bovine respiratory
syncytial virus (8.4% (uMD 4.6%, nuMD 12.1%)), bovine viral diarrhea virus (1.1%
(uMD 0%, nuMD 2.2%)), bovine parainfluenza-3 virus (27.0% (uMD 27.6%, nuMD
26.4%)), Neospora caninum (22.1% (uMD 24.4%, nuMD 19.7%)) and Toxoplasma gondii
(8.2% (uMD 12.3%, nuMD 3.9%)). No antibodies against epizootic hemorrhagic
disease virus were detected. Pregnancy rates did not differ between the two deer
populations (90.7% (uMD 90.6%, nuMD 90.9%)). Exposure to N. caninum was
associated with a reduced probability of being pregnant. uMD were more likely to
be exposed to T. gondii than nuMD. Discussion: Comparison of BCS, pregnancy rates
and pathogen exposure of uMD and nuMD showed that the health of the two
populations did not significantly differ, suggesting uMD translocations do not
pose a severe risk of pathogen transmission between mule deer populations and
that these selected pathogens do not factor in the decline of the nuMD
population. However, inclusion of additional health indicators and creation of a
robust predictive disease model are warranted to further characterize the health
of mule deer and the health risks associated with uMD translocations. These
results should be considered as part of a formal risk assessment for future uMD
translocations in southeastern British Columbia.
PMID- 29942679
TI - Cranial morphology of Sinovenator changii (Theropoda: Troodontidae) on the new
material from the Yixian Formation of western Liaoning, China.
AB - A new three-dimensionally preserved troodontid specimen consisting of most of the
skull, partial mandibles and six articulated cervical vertebrae (PMOL-AD00102)
from the Early Cretaceous Yixian Formation of Beipiao, western Liaoning, China is
identified as Sinovenator changii on the basis of a surangular with a "T"-shaped
cross-section. High-resolution computed tomographic data for the skull of this
new specimen facilitated a detailed description of the cranial anatomy of S.
changii. New diagnostic features of S. changii include a well-developed medial
shelf on the jugal, a slender bar in the parasphenoid recess, a lateral groove on
the pterygoid flange of the ectopterygoid, and the lateral surface of the
anterior cervical vertebrae bearing two pneumatic foramina. Our new observation
confirms that the braincase of Sinovenator is not as primitive as previously
suggested, although it still shows an intermediate state between derived
troodontids and non-troodontid paravians in having an initial stage of the
subotic recess and the otosphenoidal crest. Additionally, this new specimen
reveals some novel and valuable anatomical information of troodontids regarding
the quadrate-quadratojugal articulation, the stapes, the epipterygoid and the
atlantal ribs.
PMID- 29942680
TI - High prevalence of Lynx rufus gammaherpesvirus 1 in wild Vermont bobcats.
AB - Gammaherpesviruses (GHVs) are host specific DNA viruses that infect a large range
of mammalian species. These viruses preferentially target host lymphocyte cell
populations and infection may lead to morbidity or mortality in
immunocompromised, co-infected, or non-adapted hosts. In this study, we tested
for the presence of Lynx rufus gammaherpesvirus 1 (LruGHV1) in a northeastern
United States population of wild bobcats (L. rufus). We estimated prevalence of
infection and viral load in infected individuals using quantitative real-time PCR
analysis of spleen DNA from 64 Vermont bobcats. We observed an overall prevalence
of 64% using this methodology. Bobcat age was significantly positively associated
with GHV infection status, and we noted a trend for higher viral loads in young
animals, but prevalence and viral load were similar in male and female bobcats. A
single LruGHV1 variant was identified from the sequencing of the viral
glycoprotein B gene of Vermont bobcats. This gene sequence was 100% similar to
that reported in Florida bobcats and slightly variant from other isolates
identified in the Western USA. Our work suggests broad geographic distribution
and high prevalence of LruGHV1 in bobcat populations across the United States
with infection attributes that suggest horizontal transmission of the agent.
Geographic differences in viral genotype may reflect historical migration and
expansion events among bobcat populations.
PMID- 29942681
TI - Scraping marking behaviour of the largest Neotropical felids.
AB - Background: Details of how, why and in what conditions large felids make scrapes
is unknown. Here, we examined the general hypothesis about the use of scrapes for
marking proposals, as well as to communicate with other individuals to signalize
particular points or areas of interest, by studying scrape-marking behaviour of
jaguars and pumas. Methods: We surveyed by scrapes between five days and two
months mainly during dry season in five study areas from Mexico (El Eden and San
Ignacio), Belize (Cockscomb) and Brazil (Angatuba and Serra das Almas), which
differed in presence and/or abundance of jaguars and pumas. Paths were slowly
walked while searching for scrapes by teams normally composed of two people and
tracks were stored in GPS, distinguishing the type of path surveyed (unpaved
track roads, trails and cross-country). Results: We found a total of 269 felid
scrapes along 467 km of paths surveyed, obtaining a finding rate of 0.576 scrapes
per km. Most scrapes were found in car tracks (0.629 scrapes per km), followed by
trails (0.581 scrapes per km), and rarely did we find scrapes in cross country
(0.094 scrapes per km). In trails, scrapes were found in a similar frequency in
the centre and edge, whereas in car tracks they were mainly found in the edge.
There were also clear differences in the position of the scrapes between study
areas that differed in presence and/or abundance of pumas and jaguars, with
scrapes located mainly in the centre in areas only with pumas, in the centre and
in the edge in areas with a similar number of jaguars and pumas, and in the edge
in area mainly dominated by jaguars. The remarking rate tended to be higher in
one of the areas with only pumas where natural vegetation was scarcer. Felids
chose sites mainly covered by leaves and located in paths less wide, clean and
rarely used. Discussion: Scraping was a frequent behaviour in the largest felids
of America, although in some areas, scraping behaviour was rare. Scrapes seem to
be signalizing some specific areas within territories and data suggest that they
are made with the proposal of communication between individuals. It seems that a
high scraping behaviour in pumas is not related to the presence of jaguars.
PMID- 29942683
TI - Predicted effects of landscape change, sea level rise, and habitat management on
the extirpation risk of the Hawaiian common gallinule (Gallinula galeata
sandvicensis) on the island of O'ahu.
AB - We conducted a spatially explicit, stochastic, individually based population
viability analysis for the Hawaiian common gallinule (Gallinula galeata
sandvicensis), an endangered subspecies of waterbird endemic to fragmented
coastal wetlands in Hawai'i. This subspecies persists on two islands, with no
apparent movement between them. We assessed extirpation risk for birds on O'ahu,
where the resident gallinule population is made up of several fragmented
subpopulations. Data on genetic differentiation were used to delineate
subpopulations and estimate dispersal rates between them. We used sensitivity
analyses to gauge the impact of current uncertainty of vital rate parameters on
population projections, to ascertain the relative importance of gallinule vital
rates to population persistence, and to compare the efficacy of potential
management strategies. We used available sea level rise projections to examine
the relative vulnerability of O'ahu's gallinule population to habitat loss
arising from this threat. Our model predicted persistence of the island's
gallinule population at 160 years (~40 generations), but with high probabilities
of extirpation for small subpopulations. Sensitivity analyses highlighted the
importance of juvenile and adult mortality to population persistence in Hawaiian
gallinules, justifying current predator control efforts and suggesting the need
for additional research on chick and fledgling survival. Subpopulation
connectivity from dispersal had little effect on the persistence of the island
wide population, but strong effects on the persistence of smaller subpopulations.
Our model also predicted island-wide population persistence under predicted sea
level rise scenarios, but with O'ahu's largest gallinule populations losing >40%
of current carrying capacity.
PMID- 29942682
TI - Dissemination of antibiotic resistance genes associated with the sporobiota in
sediments impacted by wastewater.
AB - Aquatic ecosystems serve as a dissemination pathway and a reservoir of both
antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In
this study, we investigate the role of the bacterial sporobiota to act as a
vector for ARG dispersal in aquatic ecosystems. The sporobiota was operationally
defined as the resilient fraction of the bacterial community withstanding a harsh
extraction treatment eliminating the easily lysed fraction of the total bacterial
community. The sporobiota has been identified as a critical component of the
human microbiome, and therefore potentially a key element in the dissemination of
ARG in human-impacted environments. A region of Lake Geneva in which the
accumulation of ARG in the sediments has been previously linked to the deposition
of treated wastewater was selected to investigate the dissemination of tet(W) and
sul1, two genes conferring resistance to tetracycline and sulfonamide,
respectively. Analysis of the abundance of these ARG within the sporobiome
(collection of genes of the sporobiota) and correlation with community
composition and environmental parameters demonstrated that ARG can spread across
the environment with the sporobiota being the dispersal vector. A highly abundant
OTU affiliated with the genus Clostridium was identified as a potential specific
vector for the dissemination of tet(W), due to a strong correlation with tet(W)
frequency (ARG copy numbers/ng DNA). The high dispersal rate, long-term survival,
and potential reactivation of the sporobiota constitute a serious concern in
terms of dissemination and persistence of ARG in the environment.
PMID- 29942684
TI - Monitoring monthly surface water dynamics of Dongting Lake using Sentinel-1 data
at 10 m.
AB - High temporal resolution water distribution maps are essential for surface water
monitoring because surface water exhibits significant inner-annual variation.
Therefore, high-frequency remote sensing data are needed for surface water
mapping. Dongting Lake, the second-largest freshwater lake in China, is famous
for the seasonal fluctuations of its inundation extents in the middle reaches of
the Yangtze River. It is also greatly affected by the Three Gorges Project. In
this study, we used Sentinel-1 data to generate surface water maps of Dongting
Lake at 10 m resolution. First, we generated the Sentinel-1 time series
backscattering coefficient for VH and VV polarizations at 10 m resolution by
using a monthly composition method. Second, we generated the thresholds for
mapping surface water at 10 m resolution with monthly frequencies using Sentinel
1 data. Then, we derived the monthly surface water distribution product of
Dongting Lake in 2016, and finally, we analyzed the inner-annual surface water
dynamics. The results showed that: (1) The thresholds were -21.56 and -15.82 dB
for the backscattering coefficients for VH and VV, respectively, and the overall
accuracy and Kappa coefficients were above 95.50% and 0.90, respectively, for the
VH backscattering coefficient, and above 94.50% and 0.88, respectively, for the
VV backscattering coefficient. The VV backscattering coefficient achieved lower
accuracy due to the effect of the wind causing roughness on the surface of the
water. (2) The maximum and minimum areas of surface water were 2040.33 km2 in
July, and 738.89 km2 in December. The surface water area of Dongting Lake varied
most significantly in April and August. The permanent water acreage in 2016 was
556.35 km2, accounting for 19.65% of the total area of Dongting Lake, and the
acreage of seasonal water was 1525.21 km2. This study proposed a method to
automatically generate monthly surface water at 10 m resolution, which may
contribute to monitoring surface water in a timely manner.
PMID- 29942685
TI - Is publication bias present in gastroenterological research? An analysis of
abstracts presented at an annual congress.
AB - Background: Publication bias is the tendency of investigators, reviewers, and
editors to submit or accept manuscripts for publication based on their direction
or strength of findings. In this study, we investigated if publication bias was
present in gastroenterological research by evaluating abstracts at Americas
Hepato-Pancreato-Biliary Congresses from 2011 to 2013. Methods: We searched
Google, Google Scholar, and PubMed to locate the published reports of research
described in these abstracts. If a publication was not found, a second
investigator searched to verify nonpublication. If abstract publication status
remained undetermined, authors were contacted regarding reasons for
nonpublication. For articles reaching publication, the P value, study design,
time to publication, citation count, and journals in which the published report
appeared were recorded. Results: Our study found that of 569 abstracts presented,
297 (52.2%) reported a P value. Of these, 254 (85.5%) contained P values
supporting statistical significance. The abstracts reporting a statistically
significant outcome were twice as likely to reach publication than abstracts with
no significant findings (OR 2.10, 95% CI [1.06-4.14]). Overall, 243 (42.7%)
abstracts reached publication. The mean time to publication was 14 months and a
median time of nine months. Conclusion: In conclusion, we found evidence for
publication bias in gastroenterological research. Abstracts with significant P
values had a higher probability of reaching publication. More than half of
abstracts presented from 2011 to 2013 failed to reach publication. Readers should
take these findings into consideration when reviewing medical literature.
PMID- 29942686
TI - Vertical stratification of plant-pollinator interactions in a temperate
grassland.
AB - Visitation of plants by different pollinators depends on individual plant traits,
spatial context, and other factors. A neglected aspect of small-scale variation
of plant-pollinator interactions is the role of vertical position of flowers. We
conducted a series of experiments to study vertical stratification of plant
pollinator interactions in a dry grassland. We observed flower visitors on cut
inflorescences of Centaurea scabiosa and Inula salicina placed at different
heights above ground in two types of surrounding vegetation: short and tall. Even
at such a small-scale, we detected significant shift in total visitation rate of
inflorescences in response to their vertical position. In short vegetation,
inflorescences close to the ground were visited more frequently, while in tall
vegetation, inflorescences placed higher received more visits. Moreover, we found
major differences in the composition of the pollinator community on flowers at
different heights. In a second experiment, we measured flower visitation rate in
inflorescences of Salvia verticillata of variable height. Total flower visitation
rate increased markedly with inflorescence height in this case. Data on seed set
of individual plants provide evidence for a corresponding positive pollinator
mediated selection on increased inflorescence height. Overall, our results
demonstrate strong vertical stratification of plant-pollinator interactions at
the scale of mere decimetres. This may have important ecological as well as
evolutionary implications.
PMID- 29942687
TI - Melatonin significantly influences seed germination and seedling growth of Stevia
rebaudiana Bertoni.
AB - Background: Melatonin (MEL) is a signaling molecule in plants that affects
developmental processes during vegetative and reproductive growth. Investigations
have proved that exogenously applied MEL also has the potential to improve seed
germination and plant development. Methods: In the present study, seeds of
stevia, a species with a very low germination rate, were germinated on an agar
gel (AG) containing MEL at various concentrations (5, 20, 100, and 500 uM) in
light. Seeds germinated on AG without MEL were used as controls. For the first 24
or 48 h of germination, the seeds were maintained in darkness as a pre-incubation
step. Some seeds were not exposed to this pre-incubation step. Results: At
concentrations of 20 and 5 uM, MEL significantly improved germination, but only
in seeds pre-incubated in darkness for 24 h (p < 0.001). At concentrations of 100
and 500 uM, MEL had an inhibitory effect on germination, regardless of the pre
incubation time. Melatonin also affected plantlet properties. At a concentration
of 20 uM, MEL increased plantlet fresh weight and leaf numbers. At a
concentration of 5 uM, it promoted plantlet height. Regarding root development,
the most favorable MEL concentration was 500 uM. Biochemical analysis revealed
that MEL promoted higher pigment concentrations but hampered superoxide dismutase
activity. On the other hand, the concentrations of sugars and phenolics, as well
as the activities of catalase and peroxidase, increased at a MEL concentration of
500 uM. Discussion: The results suggest that MEL can improve germination of
positively photoblastic stevia seeds and that it can play a role in plantlet
development. However, the effects observed in the present study depended on the
quantity of MEL that was applied.
PMID- 29942688
TI - Evaluation of the effect of chickenpox vaccination on shingles epidemiology using
agent-based modeling.
AB - Background: Biological interactions between varicella (chickenpox) and herpes
zoster (shingles), two diseases caused by the varicella zoster virus (VZV),
continue to be debated including the potential effect on shingles cases following
the introduction of universal childhood chickenpox vaccination programs. We
investigated how chickenpox vaccination in Alberta impacts the incidence and age
distribution of shingles over 75 years post-vaccination, taking into
consideration a variety of plausible theories of waning and boosting of immunity.
Methods: We developed an agent-based model representing VZV disease,
transmission, vaccination states and coverage, waning and boosting of immunity in
a stylized geographic area, utilizing a distance-based network. We derived
parameters from literature, including modeling, epidemiological, and immunology
studies. We calibrated our model to the age-specific incidence of shingles and
chickenpox prior to vaccination to derive optimal combinations of duration of
boosting (DoB) and waning of immunity. We conducted paired simulations with and
without implementing chickenpox vaccination. We computed the count and cumulative
incidence rate of shingles cases at 10, 25, 50, and 75 years intervals, following
introduction of vaccination, and compared the difference between runs with
vaccination and without vaccination using the Mann-Whitney U-test to determine
statistical significance. We carried out sensitivity analyses by increasing and
lowering vaccination coverage and removing biological effect of boosting.
Results: Chickenpox vaccination led to a decrease in chickenpox cases. The
cumulative incidence of chickenpox had dropped from 1,254 cases per 100,000
person-years pre chickenpox vaccination to 193 cases per 100,000 person-years 10
years after the vaccine implementation. We observed an increase in the all-ages
shingles cumulative incidence at 10 and 25 years post chickenpox vaccination and
mixed cumulative incidence change at 50 and 75 years post-vaccination. The
magnitude of change was sensitive to DoB and ranged from an increase of 22-100
per 100,000 person-years at 10 years post-vaccination for two and seven years of
boosting respectively (p < 0.001). At 75 years post-vaccination, cumulative
incidence ranged from a decline of 70 to an increase of 71 per 100,000 person
years for two and seven years of boosting respectively (p < 0.001). Sensitivity
analyses had a minimal impact on our inferences except for removing the effect of
boosting. Discussion: Our model demonstrates that over the longer time period,
there will be a reduction in shingles incidence driven by the depletion of the
source of shingles reactivation; however in the short to medium term some age
cohorts may experience an increase in shingles incidence. Our model offers a
platform to further explore the relationship between chickenpox and shingles,
including analyzing the impact of different chickenpox vaccination schedules and
cost-effectiveness studies.
PMID- 29942689
TI - Biodegradation of Crystal Violet dye by bacteria isolated from textile industry
effluents.
AB - Industrial effluent containing textile dyes is regarded as a major environmental
concern in the present world. Crystal Violet is one of the vital textile dyes of
the triphenylmethane group; it is widely used in textile industry and known for
its mutagenic and mitotic poisoning nature. Bioremediation, especially through
bacteria, is becoming an emerging and important sector in effluent treatment.
This study aimed to isolate and identify Crystal Violet degrading bacteria from
industrial effluents with potential use in bioremediation. The decolorizing
activity of the bacteria was measured using a photo electric colorimeter after
aerobic incubation in different time intervals of the isolates. Environmental
parameters such as pH, temperature, initial dye concentration and inoculum size
were optimized using mineral salt medium containing different concentration of
Crystal Violet dye. Complete decolorizing efficiency was observed in a mineral
salt medium containing up to 150 mg/l of Crystal Violet dye by 10% (v/v)
inoculums of Enterobacter sp. CV-S1 tested under 72 h of shaking incubation at
temperature 35 degrees C and pH 6.5. Newly identified bacteria Enterobacter sp.
CV-S1, confirmed by 16S ribosomal RNA sequencing, was found as a potential
bioremediation biocatalyst in the aerobic degradation/de-colorization of Crystal
Violet dye. The efficiency of degrading triphenylmethane dye by this isolate,
minus the supply of extra carbon or nitrogen sources in the media, highlights the
significance of larger-scale treatment of textile effluent.
PMID- 29942690
TI - Effects of equal-volume resistance training with different training frequencies
in muscle size and strength in trained men.
AB - Background: The objective of the present study was to compare the effects of
equal-volume resistance training (RT) performed with different training
frequencies on muscle size and strength in trained young men. Methods: Sixteen
men with at least one year of RT experience were divided into two groups, G1 and
G2, that trained each muscle group once and twice a week, respectively, for 10
weeks. Elbow flexor muscle thickness (MT) was measured using a B-Mode ultrasound
and concentric peak torque of elbow extensors and flexors were assessed by an
isokinetic dynamometer. Results: ANOVA did not reveal group by time interactions
for any variable, indicating no difference between groups for the changes in MT
or PT of elbow flexors and extensors. Notwithstanding, MT of elbow flexors
increased significantly (3.1%, P < 0.05) only in G1. PT of elbow flexors and
extensors did not increase significantly for any group. Discussion: The present
study suggest that there were no differences in the results promoted by equal
volume resistance training performed once or twice a week on upper body muscle
strength in trained men. Only the group performing one session per week
significantly increased the MT of their elbow flexors. However, with either once
or twice a week training, adaptations appear largely minimal in previously
trained males.
PMID- 29942691
TI - Weak population structure in the ant Formica fusca.
AB - Dispersal is a fundamental trait of a species' biology. High dispersal results in
weakly structured or even panmictic populations over large areas, whereas weak
dispersal enables population differentiation and strong spatial structuring. We
report on the genetic population structure in the polygyne ant Formica fusca and
the relative contribution of the dispersing males and females to this. We sampled
12 localities across a ~35 km2 study area in Finland and generated mitochondrial
DNA (mtDNA) haplotype data and microsatellite data. First, we assessed queen
dispersal by estimating population differentiation from mtDNA haplotype data.
Second, we analysed nuclear DNA microsatellite data to determine overall
population genetic substructure in the study area with principal components
analysis, Bayesian clustering, hierarchical F statistics and testing for evidence
of isolation-by-distance. Third, we directly compared genetic differentiation
estimates from maternally inherited mtDNA and bi-parentally inherited DNA
microsatellites to test for sex-bias in dispersal. Our results showed no
significant spatial structure or isolation by distance in neither mtDNA nor DNA
microsatellite data, suggesting high dispersal of both sexes across the study
area. However, mitochondrial differentiation was weaker (Fst-mt = 0.0047) than
nuclear differentiation (Fst-nuc = 0.027), which translates into a sixfold larger
female migration rate compared to that of males. We conclude that the weak
population substructure reflects high dispersal in both sexes, and it is
consistent with F. fusca as a pioneer species exploiting unstable habitats in
successional boreal forests.
PMID- 29942692
TI - A Miocene pygmy right whale fossil from Australia.
AB - Neobalaenines are an enigmatic group of baleen whales represented today by a
single living species: the pygmy right whale, Caperea marginata, found only in
the Southern Hemisphere. Molecular divergence estimates date the origin of pygmy
right whales to 22-26 Ma, yet so far there are only three confirmed fossil
occurrences. Here, we describe an isolated periotic from the latest Miocene of
Victoria (Australia). The new fossil shows all the hallmarks of Caperea, making
it the second-oldest described neobalaenine, and the oldest record of the genus.
Overall, the new specimen resembles C. marginata in its external morphology and
details of the cochlea, but is more archaic in it having a hypertrophied
suprameatal area and a greater number of cochlear turns. The presence of Caperea
in Australian waters during the Late Miocene matches the distribution of the
living species, and supports a southern origin for pygmy right whales.
PMID- 29942694
TI - A comparative study of the gastric ossicles of Trichodactylidae crabs (Brachyura:
Decapoda) with comments on the role of diet and phylogeny in shaping
morphological traits.
AB - The gastric armature of decapod foregut is a feeding structure that sparks
controversial debates about the role dietary and historical components have in
shaping its morphological traits. Having previous information about the natural
diet is an interesting way to gather evidence on this issue. For the present
study, we analyzed the morphological traits of gastric ossicles involved directly
in the maceration of food in nine species of freshwater crabs of the family
Trichodactylidae (Brachyura: Decapoda) representing five genera, three tribes and
two subfamilies. The analyzed gastric ossicles were quite consistent among
closely related species, suggesting that the observed traits had a clear
phylogenetic component. However, it was also noted that the morphological traits
of the gastric teeth of trichodactylid crabs match well with the natural diet and
presented likeness with general features of other species with a similar trophic
habit. We discuss the influence of phylogeny and function on the design of
morphological traits and propose to quantify the role of phylogeny and function
in shaping morphological traits through the analysis of phylogenetic signals.
PMID- 29942693
TI - The effect of running versus cycling high-intensity intermittent exercise on
local tissue oxygenation and perceived enjoyment in 18-30-year-old sedentary men.
AB - Background: High-intensity interval training (HIIT) has been proposed as a time
efficient exercise format to improve exercise adherence, thereby targeting the
chronic disease burden associated with sedentary behaviour. Exercise mode
(cycling, running), if self-selected, will likely affect the physiological and
enjoyment responses to HIIT in sedentary individuals. Differences in
physiological and enjoyment responses, associated with the mode of exercise,
could potentially influence the uptake and continued adherence to HIIT. It was
hypothesised that in young sedentary men, local and systemic oxygen utilisation
and enjoyment would be higher during a session of running HIIT, compared to a
session of cycling HIIT. Methods: A total of 12 sedentary men (mean +/- SD; age
24 +/- 3 years) completed three exercise sessions: a maximal incremental exercise
test on a treadmill (MAX) followed by two experiment conditions, (1) free-paced
cycling HIIT on a bicycle ergometer (HIITCYC) and (2) constant-paced running HIIT
on a treadmill ergometer (HIITRUN). Deoxygenated haemoglobin (HHb) in the
gastrocnemius (GN), the left vastus lateralis (LVL) and the right vastus
lateralis (RVL) muscles, oxygen consumption (VO2), heart rate (HR), ratings of
perceived exertion (RPE) and physical activity enjoyment (PACES) were measured
during HIITCYC and HIITRUN. Results: There was a higher HHb in the LVL (p =
0.001) and RVL (p = 0.002) sites and a higher VO2 (p = 0.017) and HR (p < 0.001)
during HIITCYC, compared to HIITRUN. RPE was higher (p < 0.001) and PACES lower
(p = 0.032) during HIITCYC compared to HIITRUN. Discussion: In sedentary
individuals, free-paced cycling HIIT produces higher levels of physiological
stress when compared to constant-paced running HIIT. Participants perceived
running HIIT to be more enjoyable than cycling HIIT. These findings have
implications for selection of mode of HIIT for physical stress, exercise
enjoyment and compliance.
PMID- 29942695
TI - Low resolution scans can provide a sufficiently accurate, cost- and time
effective alternative to high resolution scans for 3D shape analyses.
AB - Background: Advances in 3D shape capture technology have made powerful shape
analyses, such as geometric morphometrics, more feasible. While the highly
accurate micro-computed tomography (uCT) scanners have been the "gold standard,"
recent improvements in 3D surface scanners may make this technology a faster,
portable, and cost-effective alternative. Several studies have already compared
the two devices but all use relatively large specimens such as human crania. Here
we perform shape analyses on Australia's smallest rodent to test whether a 3D
scanner produces similar results to a uCT scanner. Methods: We captured 19
delicate mouse (Pseudomys delicatulus) crania with a uCT scanner and a 3D scanner
for geometric morphometrics. We ran multiple Procrustes ANOVAs to test how
variation due to scan device compared to other sources such as biologically
relevant variation and operator error. We quantified operator error as levels of
variation and repeatability. Further, we tested if the two devices performed
differently at classifying individuals based on sexual dimorphism. Finally, we
inspected scatterplots of principal component analysis (PCA) scores for non
random patterns. Results: In all Procrustes ANOVAs, regardless of factors
included, differences between individuals contributed the most to total
variation. The PCA plots reflect this in how the individuals are dispersed.
Including only the symmetric component of shape increased the biological signal
relative to variation due to device and due to error. 3D scans showed a higher
level of operator error as evidenced by a greater spread of their replicates on
the PCA, a higher level of multivariate variation, and a lower repeatability
score. However, the 3D scan and uCT scan datasets performed identically in
classifying individuals based on intra-specific patterns of sexual dimorphism.
Discussion: Compared to uCT scans, we find that even low resolution 3D scans of
very small specimens are sufficiently accurate to classify intra-specific
differences. We also make three recommendations for best use of low resolution
data. First, we recommend that extreme caution should be taken when analyzing the
asymmetric component of shape variation. Second, using 3D scans generates more
random error due to increased landmarking difficulty, therefore users should be
conservative in landmark choice and avoid multiple operators. Third, using 3D
scans introduces a source of systematic error relative to uCT scans, therefore we
recommend not combining them when possible, especially in studies expecting
little biological variation. Our findings support increased use of low resolution
3D scans for most morphological studies; they are likely also applicable to low
resolution scans of large specimens made in a medical CT scanner. As most
vertebrates are relatively small, we anticipate our results will bolster more
researchers in designing affordable large scale studies on small specimens with
3D surface scanners.
PMID- 29942696
TI - Comprehensive analysis of mitogen-activated protein kinase cascades in
chrysanthemum.
AB - Background: Mitogen-activated protein kinase (MAPK) cascades, an important type
of pathway in eukaryotic signaling networks, play a key role in plant defense
responses, growth and development. Methods: Phylogenetic analysis and conserved
motif analysis of the MKK and MPK families in Arabidopsis thaliana, Helianthus
annuus and Chrysanthemum morifolium classified MKK genes and MPK genes. qRT-PCR
was used for the expression patterns of CmMPK and CmMKK genes, and yeast two
hybrid assay was applied to clear the interaction between CmMPKs and CmMKKs.
Results: We characterized six MKK genes and 11 MPK genes in chrysanthemum based
on transcriptomic sequences and classified these genes into four groups. qRT-PCR
analysis demonstrated that CmMKKs and CmMPKs exhibited various expression
patterns in different organs of chrysanthemum and in response to abiotic stresses
and phytohormone treatments. Furthermore, a yeast two-hybrid assay was applied to
analyze the interaction between CmMKKs and CmMPKs and reveal the MAPK cascades in
chrysanthemum. Discussion: Our data led us to propose that CmMKK4-CmMPK13 and
CmMKK2-CmMPK4 may be involved in regulating salt resistance and in the
relationship between CmMKK9 and CmMPK6 and temperature stress.
PMID- 29942697
TI - Spatio-temporal evolution of water-related ecosystem services: Taihu Basin,
China.
AB - Water-related ecosystem services (WESs) arise from the interaction between water
ecosystems and their surrounding terrestrial ecosystems. They are critical for
human well-being as well as for the whole ecological circle. An urgent service
oriented reform for the utilization and supervision of WESs can assist in
avoiding ecological risks and achieving a more sustainable development in the
Taihu Basin, China (THB). Spatially distributed models allow the multiple impacts
of land use/land cover conversion and climate variation on WESs to be estimated
and visualized efficiently, and such models can form a useful component in the
toolbox for integrated water ecosystem management. The Integrated Valuation of
Ecosystem Services and Tradeoffs model is used here to evaluate and visualize the
spatio-temporal evolution of WESs in the THB from 2000 to 2010. Results indicate
that water retention service experienced a decline from 2000 to 2005 with a
recovery after 2005, while there was ongoing water scarcity in urban areas. Both
the water purification service and the soil retention service underwent a slight
decrease over the study period. Nutrients export mainly came from developed land
and cultivated land, with the hilly areas in the south of the THB forming the
primary area for soil loss. The quantity and distribution of WESs were impacted
significantly by the shrinkage of cultivated land and the expansion of developed
land. These findings will lay a foundation for a service-oriented management of
WESs in the THB and support evidence-based decision making.
PMID- 29942698
TI - aaquetzalli is required for epithelial cell polarity and neural tissue formation
in Drosophila.
AB - Morphogenetic movements during embryogenesis require dynamic changes in
epithelial cell polarity and cytoskeletal reorganization. Such changes involve,
among others, rearrangements of cell-cell contacts and protein traffic. In
Drosophila melanogaster, neuroblast delamination during early neurogenesis is a
well-characterized process requiring a polarized neuroepithelium, regulated by
the Notch signaling pathway. Maintenance of epithelial cell polarity ensues
proper Notch pathway activation during neurogenesis. We characterize here
aaquetzalli (aqz), a gene whose mutations affect cell polarity and nervous system
specification. The aqz locus encodes a protein that harbors a domain with
significant homology to a proline-rich conserved domain of nuclear receptor co
activators. aqz expression occurs at all stages of the fly life cycle, and is
dynamic. aqz mutants are lethal, showing a disruption of cell polarity during
embryonic ventral neuroepithelium differentiation resulting in loss of epithelial
integrity and mislocalization of membrane proteins (shown by mislocalization of
Crumbs, DE-Cadherin, and Delta). As a consequence, aqz mutant embryos with
compromised apical-basal cell polarity develop spotty changes of neuronal and
epithelial numbers of cells.
PMID- 29942699
TI - Allometric shell growth in infaunal burrowing bivalves: examples of the
archiheterodonts Claibornicardia paleopatagonica (Ihering, 1903) and Crassatella
kokeni Ihering, 1899.
AB - We present two cases of study of ontogenetic allometry in outlines of bivalves
using longitudinal data, a rarity among fossils, based on the preserved post
larval record of shells. The examples are two infaunal burrowing bivalves of the
southern South America, Claibornicardia paleopatagonica (Archiheterodonta:
Carditidae) (early Paleocene) and Crassatella kokeni (Archiheterodonta:
Crassatellidae) (late Oligocene-late Miocene). Outline analyses were conducted
using a geometric morphometric approach (Elliptic Fourier Analysis), obtaining
successive outlines from shells' growth lines, which were used to reconstruct
ontogenetic trajectories. In both taxa, ontogenetic changes are characterized by
the presence of positive allometry in the extension of posterior end, resulting
in elongated adult shells. This particular allometric growth is known in others
infaunal burrowing bivalves (Claibornicardia alticostata and some Spissatella
species) and the resulting adult morphology is present in representatives of
several groups (e.g., Carditidae, Crassatellidae, Veneridae, Trigoniidae).
Taxonomic, ecological and evolutionary implications of this allometric growth
pattern are discussed.
PMID- 29942700
TI - Prevalence of extended spectrum beta lactamase and plasmid mediated quinolone
resistant genes in strains of Klebsiella pneumonia, Morganella morganii,
Leclercia adecarboxylata and Citrobacter freundii isolated from poultry in South
Western Nigeria.
AB - A serious concern is arising on the coexistence of extended-spectrum beta
lactamase (ESBL) and plasmid mediated quinolone resistance (PMQR) producing
bacteria in animal husbandry, which could be transferred to humans, especially in
strains that may not be routinely screened for resistance. This study therefore
tested the prevalence of ESBL and PMQR genes in selected bacteria isolated from
poultry faeces. Faecal droppings of birds were collected from 11 farms in five
states in South Western Nigeria. Bacteria were isolated from the samples on
cefotaxime supplemented plates and identified with MALDI-TOF. The MIC was
determined using VITEK system and resistance genes were detected with PCR. A
total of 350 strains were isolated from different samples and selected strains
were identified as 23 Klebsiella pneumonia, 12 Morganella morganii, seven
Leclercia adecarboxylata and one Citrobacter freundii. All the species were
resistant to gentamycin, trimethoprim/sulphamethaxole, tobramycin, piperacillin,
cefotaxime and aztreonam (except Morganella morganii strains which were mostly
susceptible to aztreonam). All the tested strains were susceptible to imipenem,
meropenem and amikacin. All Leclercia adecarboxylata strains were resistant to
ceftazidime, cefepime and fosfomycin while all Morganella morganii strains were
resistant to fosfomycin, moxifloxacin and ciprofloxacin. All tested species were
generally sensitive to ciprofloxacin except Morganella morganii strains which
were resistant to ciprofloxacin. The resistance to ciprofloxacin, ceftazidime,
cefepime, tigercylin, colistin and fosfomycin were 65%, 40%, 23%,, 7%, 33%, 48%
respectively while the prevalence of SHV, TEM and CTX genes were 42%, 63%, 35%
respectively. 9.3% of the isolates had the three ESBL genes, 2.33% had qnrA gene,
4.65% had qnr B gene while none had qnrS gene. The most prevalent PMQR gene is
Oqxb (25.58%) while 6.98% had the qep gene. Klebsiella pneumoniae generally had
both ESBL and PMQR genes. The high prevalence of extended spectrum beta-lactamase
genes in the studied strains calls for caution in the use of beta lactam
antibiotics in poultry feeds. This is the first report of the occurrence of
extended spectrum beta-lactamase and plasmid mediated quinolone resistance genes
in Morganella morganii and Leclercia adecarboxylata strains isolated from poultry
faeces.
PMID- 29942701
TI - Floating nurseries? Scyphozoan jellyfish, their food and their rich symbiotic
fauna in a tropical estuary.
AB - Background: The anthropogenic modification of trophic pathways is seemingly
prompting the increase of jellyfish populations at the expense of planktivorous
fishes. However, gross generalizations are often made because the most basic
aspects of trophic ecology and the diverse interactions of jellyfish with fishes
remain poorly described. Here we inquire on the dynamics of food consumption of
the medusoid stage of the scyphozoan jellyfish Stomolophus meleagris and
characterize the traits and diversity of its symbiotic community. Methods: S.
meleagris and their associated fauna were sampled in surface waters between
November 2015 and April 2017 in Malaga Bay, an estuarine system at the Colombian
Pacific. Stomach contents of medusae were examined and changes in prey
composition and abundance over time analysed using a multivariate approach. The
associated fauna was identified and the relationship between the size of medusae
and the size those organisms tested using least-square fitting procedures.
Results: The presence of S. meleagris medusa in surface waters was seasonal. The
gut contents analysis revealed that algae, copepods and fish early life stages
were the more abundant items, and PERMANOVA analysis showed that the diet
differed within the seasons (P(perm) = 0.001) but not between seasons (P(perm) =
0.134). The majority of the collected medusae (50.4%) were associated with
individuals of 11 symbiotic species, 95.3% of them fishes, 3.1% crustaceans and
1.6% molluscs. Therefore, this study reports 10 previously unknown associations.
The bell diameter of S. meleagris was positively related to the body sizes of
their symbionts. However, a stronger fit was observed when the size relationship
between S. meleagris and the fish Hemicaranx zelotes was modelled. Discussion:
The occurrence of S. meleagris was highly seasonal, and the observed patterns of
mean body size through the seasons suggested the arrival of adult medusae to the
estuary from adjacent waters. The diet of S. meleagris in the study area showed
differences with previous reports, chiefly because of the abundance of algae that
are seemingly ingested but not digested. The low number of zooplanktonic items in
gut contents suggest the contribution of alternative food sources not easily
identifiable. The observed changes in the composition of food in the guts
probably reflect seasonal changes in the availability of prey items. The regular
pattern in the distribution of symbionts among medusae (a single symbiont per
host) and the positive host-symbiont size relationship reflects antagonistic
intraspecific and interspecific behaviour of the symbiont. This strongly suggest
that medusa represent an "economically defendable resource" that potentially
increases the survival and recruitment of the symbionts to the adult population.
We argue that, if this outcome of the symbiotic association can be proven,
scyphozoan jellyfish can be regarded as floating nurseries.
PMID- 29942702
TI - Initial response of phenology and yield components of wheat (Triticum durum L.,
CIRNO C2008) under experimental warming field conditions in the Yaqui Valley.
AB - This work evaluates the experimental warming effects on phenology and grain yield
components of wheat in the Yaqui Valley, Sonora, Mexico, using CIRNO C2008
variety from Triticum durum L., as a model during the cropping cycle of 2016-2017
(December to April). Infrared radiators were deployed to induce experimental
warming by 2 degrees C above ambient crop canopy temperature, in a temperature
free-air controlled enhancement system. Temperature was controlled by infrared
temperature sensors placed in eight plots which covered a circle of r = 1.5 m
starting five days after germination until harvest. The warming treatment caused
a reduction of phenophases occurrence starting at the stem extension phenophase.
Such phenological responses generated a significant biological cycle reduction of
14 days. Despite this delay, CIRNO C2008 completed its biological cycle
adequately. However, plant height under the warming treatment was reduced
significantly and differences were particularly observed at the final phenophases
of the vegetative cycle. Plant height correlated negatively with spikes length,
spikes mass, and number of filled grains. Warming also reduced grain yield in
33%. The warming treatment caused a stress intensity (SI = 1-yield warming/yield
control) of 39.4% and 33.2% in biomass and grain yield, respectively. The
differences in stress intensities between biomass and grain yield were based on
plant height reduction. Grain mass was not affected, demonstrating the crop
capability for remobilization and adequate distribution of elaborated substances
for the spikes under warming conditions.
PMID- 29942703
TI - How many fish? Comparison of two underwater visual sampling methods for
monitoring fish communities.
AB - Background: Underwater visual surveys (UVSs) for monitoring fish communities are
preferred over fishing surveys in certain habitats, such as rocky or coral reefs
and seagrass beds and are the standard monitoring tool in many cases, especially
in protected areas. However, despite their wide application there are potential
biases, mainly due to imperfect detectability and the behavioral responses of
fish to the observers. Methods: The performance of two methods of UVSs were
compared to test whether they give similar results in terms of fish population
density, occupancy, species richness, and community composition. Distance
sampling (line transects) and plot sampling (strip transects) were conducted at
31 rocky reef sites in the Aegean Sea (Greece) using SCUBA diving. Results: Line
transects generated significantly higher values of occupancy, species richness,
and total fish density compared to strip transects. For most species, density
estimates differed significantly between the two sampling methods. For secretive
species and species avoiding the observers, the line transect method yielded
higher estimates, as it accounted for imperfect detectability and utilized a
larger survey area compared to the strip transect method. On the other hand,
large-scale spatial patterns of species composition were similar for both
methods. Discussion: Overall, both methods presented a number of advantages and
limitations, which should be considered in survey design. Line transects appear
to be more suitable for surveying secretive species, while strip transects should
be preferred at high fish densities and for species of high mobility.
PMID- 29942704
TI - Incidence of ill-health related job loss and related social and occupational
factors. The "unfit for the job" study: a one-year follow-up study of 51,132
workers.
AB - Objective: The analysis of ill-health related job loss may be a relevant
indicator for the prioritization of actions in the workplace or in the field of
public health, as well as a target for health promotion. The aim of this study
was to analyze the medical causes, the incidence, and the characteristics of
employees medically unfit to do their job. Methods: This one-year prospective
study included all workers followed by occupational physicians in an occupational
health service in the south of France. The incidence of unfitness for work have
been grouped according to the main medical causes and analyzed. We performed a
multivariate analysis in order to adjust the observed risk of job loss based on
the age groups, sex, occupation and the activity sectors. Results: A total of 17
occupational physicians followed up 51,132 workers. The all-cause incidence of
being unfit to return to one's job was 7.80/00 (n = 398). The two main causes of
being unfit for one's job were musculoskeletal disorders (47.2%, n = 188) and
mental ill-health (38.4%, n = 153). Being over 50 years old (Odds ratio (OR)
2.63, confidence interval 95% CI [2.13-3.25]) and being a woman (OR 1.52, 95% CI
[1.21-1.91]) were associated with the all-cause unfitness, independent of
occupation and activity sector. Conclusions: Identification of occupational and
demographic determinants independently associated with ill-health related job
loss may provide significant and cost-effective arguments for health promotion
and job loss prevention.
PMID- 29942705
TI - Plant-insect interactions patterns in three European paleoforests of the late
Neogene-early-Quaternary.
AB - Plants and insects are constantly interacting in complex ways through forest
communities since hundreds of millions of years. Those interactions are often
related to variations in the climate. Climate change, due to human activities,
may have disturbed these relationships in modern ecosystems. Fossil leaf
assemblages are thus good opportunities to survey responses of plant-insect
interactions to climate variations over the time. The goal of this study is to
discuss the possible causes of the differences of plant-insect interactions'
patterns in European paleoforests from the Neogene-Quaternary transition. This
was accomplished through three fossil leaf assemblages: Willershausen, Berga
(both from the late Neogene of Germany) and Bernasso (from the early Quaternary
of France). In Willershausen it has been measured that half of the leaves
presented insect interactions, 35% of the fossil leaves were impacted by insects
in Bernasso and only 25% in Berga. The largest proportion of these interactions
in Bernasso were categorized as specialist (mainly due to galling) while in
Willershausen and Berga those ones were significantly more generalist. Contrary
to previous studies, this study did not support the hypothesis that the mean
annual precipitation and temperature were the main factors that impacted the
different plant-insect interactions' patterns. However, for the first time, our
results tend to support that the hydric seasonality and the mean temperature of
the coolest months could be potential factors influencing fossil plant-insect
interactions.
PMID- 29942706
TI - Molecular detection and phylogenetic assessment of six honeybee viruses in Apis
mellifera L. colonies in Bulgaria.
AB - Honey bee colonies suffer from various pathogens, including honey bee viruses.
About 24 viruses have been reported so far. However, six of them are considered
to cause severe infection which inflicts heavy losses on beekeeping. The aim of
this study was to investigate incidence of six honey bee viruses: deformed wing
virus (DWV), acute bee paralysis virus (ABPV), chronic bee paralysis virus
(CBPV), sacbrood virus (SBV), kashmir bee virus (KBV), and black queen cell virus
(BQCV) by a reverse transcription polymerase chain reaction (RT-PCR). A total of
250 adult honey bee samples were obtained from 50 colonies from eight apiaries
situated in three different parts of the country (South, North and West
Bulgaria). The results showed the highest prevalence of DWV followed by SBV and
ABPV, and one case of BQCV. A comparison with homology sequences available in
GenBank was performed by phylogenetic analysis, and phylogenetic relationships
were discussed in the context of newly described genotypes in the uninvestigated
South Eastern region of Europe. In conclusion, the present study has been the
first to provide sequencing data and phylogenetics analyses of some honey bee
viruses in Bulgaria.
PMID- 29942707
TI - Fish species richness is associated with the availability of landscape components
across seasons in the Amazonian floodplain.
AB - Understanding environmental biodiversity drivers in freshwater systems continues
to be a fundamental challenge in studies of their fish assemblages. The present
study seeks to determine the degree to which landscape variables of Amazonian
floodplain lakes influences fish assemblages in these environments. Fish species
richness was estimated in 15 Amazonian floodplain lakes during the high and low
water phases and correlated with the areas of four inundated wetland classes: (i)
open water, (ii) flooded herbaceous, (iii) flooded shrubs and (iv) flooded forest
estimated in different radius circular areas around each sampling site. Data were
analyzed using generalized linear models with fish species richness, total and
guilds as the dependent variable and estimates of buffered landscape areas as
explanatory variables. Our analysis identified the significance of landscape
variables in determining the diversity of fish assemblages in Amazonian
floodplain lakes. Spatial scale was also identified as a significant determinant
of fish diversity as landscape effects were more evident at larger spatial
scales. In particular, (1) total species richness was more sensitive to
variations in the landscape areas than number of species within guilds and (2)
the spatial extent of the wetland class of shrubs was consistently the more
influential on fish species diversity.
PMID- 29942708
TI - An integrative taxonomic analysis reveals a new species of lotic Hynobius
salamander from Japan.
AB - We examine the phylogenetic structure and morphological differentiation within
the Hynobius kimurae-H. boulengeri species complex-a widely-distributed group of
stream-breeding hynobiid salamanders, inhabiting montane areas of western,
central and eastern parts of Honshu Island, Japan. Phylogenetic relationships
were assessed based on analyses of mitochondrial (mtDNA) and nuclear (nuDNA) gene
fragments for a total of 51 samples representing 23 localities covering the
entire range of the species complex. Morphological study included one-way
analysis of variance (ANOVA) and principal components analysis (PCA) analyses of
26 morphometric and six meristic characters for 38 adult specimens of H. kimurae
and three adult specimens of H. boulengeri. MtDNA genealogy supported monophyly
of the H. kimurae-H. boulengeri complex, which is sister to all other Hynobius
except H. retardatus. The complex is subdivided into three major clades,
corresponding to the Eastern (Clade I) and Western (Clade II) populations of H.
kimurae sensu lato, and to H. boulengeri (Clade III). Monophyly of H. kimurae
sensu lato is only moderately supported by mtDNA, while nuDNA suggested that the
Western form of H. kimurae is closer to H. boulengeri than to the eastern form.
The time of the split of the H. kimurae-H. boulengeri complex is estimated as
late Miocene and coincides with intensive crust movement in western Japan.
Divergence between Clades I and II took place in early Pliocene and was likely
influenced by the uplift of Central Japanese Highlands. All three clades were
found to be different in a number of morphological characters, allowing us to
describe the eastern form of H. kimurae as a new species, Hynobius fossigenussp.
nov.
PMID- 29942709
TI - Starch biotransformation into isomaltooligosaccharides using thermostable alpha
glucosidase from Geobacillus stearothermophilus.
AB - The present study first identified the biotransformation of starch as a novel
preparation method was investigated using the alpha-transglucosidase-producing
Geobacillus stearothermophilus U2. Subsequently, 5 L- and 20 L-scale
fermentations were performed. After isolation and purification, liquid alpha
glucosidase preparations were obtained. Through covalent cross-linking and
adsorption cross-linking using chitosan as the carrier and glutaraldehyde as the
crosslinking agent, the conditions for immobilization of alpha-glucosidase on
chitosan were determined. Moreover, Isomaltooligosaccharides (IMOs) were then
prepared using chitosan membrane-immobilized alpha-glucosidase, beta-amylase,
pullulanase, fungal alpha-amylase and starch as substrate. The mixed syrup that
contained IMOs was evaluated and analyzed by thin-layer chromatography (TLC) and
high-performance liquid chromatography (HPLC). In addition, small-scale
preparation of IMOs was performed. These results are a strong indication that the
alpha-transglucosidase-producing G. stearothermophilus as a potential application
technique can be successfully used to prepare industrial IMOs.
PMID- 29942711
TI - Effect of human recreation on bird anti-predatory response.
AB - Wildlife perceive humans as predators, and therefore normally flushes. Flight
initiation distance (FID) is the distance a human can approach an animal at a
steady pace until it flushes. Recently, several studies showed differences in
within-species FID according to human presence by comparing urban and rural
habitats, with urban birds showing reduced FIDs. However, urban and rural
habitats also differ in structure, which might affect FID. Therefore, in order to
understand the real effect of human presence, we investigated whether differences
in FID are also present in natural habitats (forests), differing only in the
intensity of human use for recreation. We found that human frequentation had a
distinct effect on bird escape responses, with shorter FIDs in forests more
heavily frequented by humans than in forests rarely visited by humans. Whether
this finding is driven by non-random spatial distribution of personalities (shy
vs. bold) or phenotypic plasticity (habituation to humans) cannot be assessed
with our data. Studies relying on FIDs should also incorporate human recreation
intensity, as this affects the measurements strongly.
PMID- 29942712
TI - Analyzing mixing systems using a new generation of Bayesian tracer mixing models.
AB - The ongoing evolution of tracer mixing models has resulted in a confusing array
of software tools that differ in terms of data inputs, model assumptions, and
associated analytic products. Here we introduce MixSIAR, an inclusive, rich, and
flexible Bayesian tracer (e.g., stable isotope) mixing model framework
implemented as an open-source R package. Using MixSIAR as a foundation, we
provide guidance for the implementation of mixing model analyses. We begin by
outlining the practical differences between mixture data error structure
formulations and relate these error structures to common mixing model study
designs in ecology. Because Bayesian mixing models afford the option to specify
informative priors on source proportion contributions, we outline methods for
establishing prior distributions and discuss the influence of prior specification
on model outputs. We also discuss the options available for source data inputs
(raw data versus summary statistics) and provide guidance for combining sources.
We then describe a key advantage of MixSIAR over previous mixing model software
the ability to include fixed and random effects as covariates explaining
variability in mixture proportions and calculate relative support for multiple
models via information criteria. We present a case study of Alligator
mississippiensis diet partitioning to demonstrate the power of this approach.
Finally, we conclude with a discussion of limitations to mixing model
applications. Through MixSIAR, we have consolidated the disparate array of mixing
model tools into a single platform, diversified the set of available
parameterizations, and provided developers a platform upon which to continue
improving mixing model analyses in the future.
PMID- 29942710
TI - The impact of PI3K inhibitors on breast cancer cell and its tumor
microenvironment.
AB - The phosphoinositide 3-kinase (PI3K) pathway shows frequent aberrant alterations
and pathological activation in breast cancer cells. While PI3K inhibitors have
not achieved expectant therapeutic efficacy in clinical trials, and several
studies provide promising combination strategies to substantially maximize
therapeutic outcomes. Besides its direct impact on regulating cancer cells
survival, PI3K inhibitors are also demonstrated to have an immunomodulatory
impact based on the tumor microenvironment. Inhibition of the leukocyte-enriched
PI3K isoforms may break immune tolerance and restore cytotoxic T cell activity by
reprogramming the tumor microenvironment. In addition, PI3K inhibitors have
pleiotropic effects on tumor angiogenesis and even induce tumor vascular
normalization. In this review, we discuss the mechanism of PI3K inhibitor
suppression of breast cancer cells and modulation of the tumor microenvironment
in order to provide further thoughts for breast cancer treatment.
PMID- 29942713
TI - Patients with chronic periodontitis present increased risk for primary Sjogren
syndrome: a nationwide population-based cohort study.
AB - Many reports have mentioned the association between chronic periodontitis (CP)
and primary Sjogren syndrome (pSS). However, no cohort study has been performed
for the risk of pSS in patients with CP. In this study, we evaluated the risk of
pSS from CP exposure in a nationwide population-based cohort study in Taiwan. We
studied the claims data of Taiwanese population from 2001 to 2012. We identified
76,765 patients with CP from the National Health Insurance Database in Taiwan. We
also selected 76,765 controls that were randomly frequency matched by age, sex,
and index year from the general population. We analyzed the risk of pSS by using
Cox proportional hazards regression models including sex, age, and comorbidities.
In this study, 76,765 patients with CP (mean age: 40.8 years) and 76,765 controls
(mean age: 41.0 years) were followed-up for 8.54 and 8.49 years, respectively. A
total of 869 cases of pSS were identified in CP cohort and 483 cases in non-CP
cohort. Multivariate Cox regression analysis indicated that the incidence rate of
pSS was significantly higher in CP cohort than those who in non-CP cohort
(adjusted HR: 1.79, 95% CI [1.60-2.00]). Taken together, this nationwide
retrospective cohort study demonstrated that the risk of pSS was significantly
higher in patients with CP than in the general population. The association
between CP and pSS was significant in the female group.
PMID- 29942714
TI - Comparison of the toxic effects of different mycotoxins on porcine and mouse
oocyte meiosis.
AB - Background: Aflatoxin B1 (AFB1), deoxynivalenol (DON), HT-2, ochratoxin A (OTA),
zearalenone (ZEA) are the most common mycotoxins that are found in corn-based
animal feed which have multiple toxic effects on animals and humans. Previous
studies reported that these mycotoxins impaired mammalian oocyte quality.
However, the effective concentrations of mycotoxins to animal oocytes were
different. Methods: In this study we aimed to compare the sensitivity of mouse
and porcine oocytes to AFB1, DON, HT-2, OTA, and ZEA for mycotoxin research. We
adopted the polar body extrusion rate of mouse and porcine oocyte as the standard
for the effects of mycotoxins on oocyte maturation. Results and Discussion: Our
results showed that 10 MUM AFB1 and 1 MUM DON significantly affected porcine
oocyte maturation compared with 50 MUM AFB1 and 2 MUM DON on mouse oocytes.
However, 10 nM HT-2 significantly affected mouse oocyte maturation compared with
50 nM HT-2 on porcine oocytes. Moreover, 5 MUM OTA and 10 MUM ZEA significantly
affected porcine oocyte maturation compared with 300 MUM OTA and 50 MUM ZEA on
mouse oocytes. In summary, our results showed that porcine oocytes were more
sensitive to AFB1, DON, OTA, and ZEA than mouse oocytes except HT-2 toxin.
PMID- 29942715
TI - Psychological, pharmacological, and combined treatments for binge eating
disorder: a systematic review and meta-analysis.
AB - Objective: To systematically review the efficacy of psychological,
pharmacological, and combined treatments for binge eating disorder (BED). Method:
Systematic search and meta-analysis. Results: We found 45 unique studies with
low/medium risk of bias, and moderate support for the efficacy of cognitive
behavior therapy (CBT) and CBT guided self-help (with moderate quality of
evidence), and modest support for interpersonal psychotherapy (IPT), selective
serotonin reuptake inhibitors (SSRI), and lisdexamfetamine (with low quality of
evidence) in the treatment of adults with BED in terms of cessation of or
reduction in the frequency of binge eating. The results on weight loss were
disappointing. Only lisdexamfetamine showed a very modest effect on weight loss
(low quality of evidence). While there is limited support for the long-term
effect of psychological treatments, we have currently no data to ascertain the
long-term effect of drug treatments. Some undesired side effects are more common
in drug treatment compared to placebo, while the side effects of psychological
treatments are unknown. Direct comparisons between pharmaceutical and
psychological treatments are lacking as well as data to generalize these results
to adolescents. Conclusion: We found moderate support for the efficacy of CBT and
guided self-help for the treatment of BED. However, IPT, SSRI, and
lisdexamfetamine received only modest support in terms of cessation of or
reduction in the frequency of binge eating. The lack of long-term follow-ups is
alarming, especially with regard to medication. Long-term follow-ups,
standardized assessments including measures of quality of life, and the study of
underrepresented populations should be a priority for future research.
PMID- 29942716
TI - Effects of anthropogenic wildfire in low-elevation Pacific island vegetation
communities in French Polynesia.
AB - Anthropogenic (or human-caused) wildfire is an increasingly important driver of
ecological change on Pacific islands including southeastern Polynesia, but fire
ecology studies are almost completely absent for this region. Where observations
do exist, they mostly represent descriptions of fire effects on plant communities
before the introduction of invasive species in the modern era. Understanding the
effects of wildfire in southeastern Polynesian island vegetation communities can
elucidate which species may become problematic invasives with continued wildfire
activity. We investigate the effects of wildfire on vegetation in three low
elevation sites (45-379 m) on the island of Mo'orea in the Society Islands,
French Polynesia, which are already heavily impacted by past human land use and
invasive exotic plants, but retain some native flora. In six study areas (three
burned and three unburned comparisons), we placed 30 transects across sites and
collected species and abundance information at 390 points. We analyzed each local
community of plants in three categories: natives, those introduced by Polynesians
before European contact (1767 C.E.), and those introduced since European contact.
Burned areas had the same or lower mean species richness than paired comparison
sites. Although wildfire did not affect the proportions of native and introduced
species, it may increase the abundance of introduced species on some sites. Non
metric multidimensional scaling indicates that (not recently modified) comparison
plant communities are more distinct from one another than are those on burned
sites. We discuss conservation concerns for particular native plants absent from
burned sites, as well as invasive species (including Lantana camara and
Paraserianthes falcataria) that may be promoted by fire in the Pacific.
PMID- 29942717
TI - Influences for Gender Disparity in Academic Psychiatry in the United States.
AB - Introduction Academic undertakings, including research, lead to career
progression. However, the career paths of female psychiatrists appear to diverge
significantly from that of their male counterparts. This article reviews the
pervasiveness of the trend of women being less likely to pursue active research
in psychiatry. In addition, we examine the correlation between academic rank and
research productivity. Methods We searched the American Medical Association's
(AMA) Fellowship and Residency Electronic Interactive Database (FREIDA) to
identify training programs for psychiatry. A total of 5234 psychiatrists met our
inclusion criteria. The gender, academic rank, research work, and h-index of
faculty members were compared. The ratio of women reaching senior ranks as
compared to men was also calculated. The Scopus database was used to determine
the h-index of the individuals included in this study. Data analysis was done
with SPSS 22.0 Release 2013 (IBM SPSS Statistics for Windows, IBM, Armonk, NY,
USA). Kruskal-Wallis and Mann-Whitney U tests were used where required, with the
P-value set at less than 0.05. Results In our study sample, 2181 (42%) of the
psychiatrists were women. However, according to the information obtained from the
websites of 23 programs, few women reached higher ranks, full professorship, or
positions such as the chairperson of a program, and only 9% of women achieved the
designation of chairperson of the psychiatry department, with men representing
the other 91%. Higher academic rank correlated with higher h-index. A
statistically-significant difference between the genders in terms of h-index was
found for the assistant professor rank as well. However, this difference was not
observed at the level of an associate professor. Conclusions Despite adequate
representation of women in the academic workforce in psychiatry, there appears to
be a discrepancy in the research productivity of the two genders. This study
highlights the need for targeted interventions to address gender disparities in
academic psychiatry.
PMID- 29942719
TI - A Sweet Diagnosis for a Non-Resolving Rash.
AB - Subcutaneous Sweet's syndrome (SSS) is a rare variant of Sweet's syndrome (SS),
clinically characterized by erythematous plaques or nodules with a histologic
pattern demonstrating a neutrophilic panniculitis (NP). We report a case of a 74
year-old woman with myelodysplastic syndrome (MDS) who presented with persistent
fever, malaise, and non-resolving generalized erythematous nodules and was found
to have an MDS-related SSS. SSS should be entertained and other causes of NP
should be excluded prior to treating a patient with systemic corticosteroids.
Early diagnosis of SSS in a patient not responding to broad-spectrum antibiotics
is crucial as it helps to minimize unnecessary prolonged antibiotics exposure in
this era of antimicrobial resistance. In patients with frequent relapses, a slow
corticosteroid taper could be beneficial.
PMID- 29942718
TI - Thromboelastography With Platelet Mapping is Not an Effective Measure of Platelet
Inhibition in Patients With Spontaneous Intracerebral Hemorrhage on Antiplatelet
Therapy.
AB - Thromboelastography with platelet mapping (TEG-PM) is a modality to measure
platelet function, especially in patients taking antiplatelet medications. It
consists of two components: arachidonic acid (AA), which is sensitive to aspirin,
and adenosine diphosphate (ADP), which is sensitive to clopidogrel. In patients
with spontaneous intracerebral hemorrhages (sICH), the clinical interpretation of
platelet mapping is unclear. The objective of this study was to evaluate TEG-PM
in patients with sICH on aspirin and/or clopidogrel who receive platelet
transfusions. This study was an IRB-approved, retrospective case-control study
over three years at an academic medical center. Adult patients with sICH were
included if they had an admission computed tomography head (CTH) and platelet
mapping followed by a repeat platelet mapping and CTH post platelet transfusion.
A threshold of 50% inhibition was used as the benchmark for both ADP and AA
inhibition. Around 248 subjects with sICH were identified, and 107 were excluded
for incomplete documentation, leaving 141 for analysis. Of these, nine met our
inclusion criteria. No statistical significance was found on the antithrombotic
effects of aspirin or clopidogrel on TEG-PM (p=1.00 for both). Sensitivity and
specificity of TEG-PM for clopidogrel was 100% and 42.9%, respectively, and 80%
and 0%, respectively, for aspirin. Platelet transfusion did not significantly
change AA or ADP inhibition (p=1.00). Hemorrhagic expansion on CTH was not
associated with a decrease AA or ADP inhibition (p=1.00). TEG-PM is not an
effective measure of platelet inhibition in sICH patients who were on
antiplatelet medications and is not a reliable measurement following platelet
transfusion.
PMID- 29942720
TI - Permanent Interstitial Brachytherapy for Previously Irradiated Head and Neck
Cancer.
AB - OBJECTIVE: To evaluate our institutional experience using brachytherapy for the
re-irradiation of the head and neck. STUDY DESIGN/METHODS: We reviewed the
records of patients who received brachytherapy for head and neck cancer in a
previously irradiated field between 2007 and 2016. RESULTS: Sixty-nine patients
received brachytherapy-based re-irradiation. Forty-nine patients (71%) were
treated for recurrent cancers, 15 patients (22%) had second primary cancers, and
five patients (7%) were treated for persistent tumors. The median dose was 90 Gy
(range 30-180). Median follow-up was 3.0 years for surviving patients and 0.6
years for all patients. Overall survival at one, three, and five years was 58%,
19%, and 12%, respectively. Local control at one, three, and five years was 55%,
38%, and 28%, respectively. A disease-free interval of less than one year was
associated with significantly worse local control (p=.04). Patients who received
brachytherapy for a neck disease had significantly worse locoregional control
than those who received brachytherapy for mucosal disease (heart rate (HR) 2.14,
95% CI 1.00-4.56, p=.05). Patients who had an extranodal extension had
significantly worse overall survival than those without an extranodal extension
(HR 2.57, 95% CI 1.28-5.37, p=.008). Seventy-four percent of patients who had
pain before brachytherapy (with or without surgery) had an improvement of
symptoms. Acute and chronic toxicity of at least Common Terminology Criteria for
Adverse Events Grade 3 was seen in 27% and 19% of the patients, respectively.
CONCLUSIONS: Brachytherapy-based re-irradiation is an effective approach for
patients undergoing re-irradiation for head and neck cancer. Brachytherapy may be
more effective for mucosal recurrences than neck recurrences.
PMID- 29942721
TI - The Impact of a Sibling's Death in Intensive Care Unit: Are We Doing Enough to
Help Them?
AB - As physicians, we have lost many children who were under our care despite our
best efforts. For most of us, after breaking the news to the family, we move on
to treat our next patient who needs help. However, the family and most
importantly the siblings have a harder time. The aim of this report is to try to
understand how they cope with the loss of a sibling who was previously in
intensive care unit.
PMID- 29942722
TI - Levels of Anxiety and Depression Before Palliative Reirradiation Are Comparable
to Those Before First Palliative Radiotherapy.
AB - INTRODUCTION: The purpose of this study was to evaluate whether or not patients
scheduled for the reirradiation of a previously treated target volume report
reduced levels of anxiety and depression, compared to patients receiving their
first course of palliative radiotherapy, e.g., because they are familiar with the
process of treatment planning and delivery. METHODS: A retrospective comparison
of two groups of patients (37% reirradiated, overall 102 patients), which scored
their symptoms before palliative radiotherapy with the Edmonton symptom
assessment system (ESAS). RESULTS: The two groups differed significantly with
regard to the incidence of bone metastases, which was higher in the reirradiation
group. Mean anxiety and depression scores were not significantly different
between the two groups. The same was true for the proportion of patients with
symptom scores >=4. Analyses limited to patients treated for bone metastases
revealed no significant differences either. Survival was similar, too.
CONCLUSION: The facts that similar ESAS scores of anxiety and depression were
observed and that prognosis was comparable suggest that the magnitude of these
symptoms might be associated with the presence of incurable cancer itself (or the
related somatic symptom burden) rather than the setting in which palliative
radiotherapy is performed.
PMID- 29942723
TI - Necrotizing Crescentic Glomerulonephritis Complicating Bivalvular Bacterial
Endocarditis.
AB - In the setting of an increasing incidence of endocarditis in the United States,
we report a patient with necrotizing crescentic glomerulonephritis (GN)
associated with native valve bacterial endocarditis due to Streptococcus
parasanguinis. He was started on appropriate antibiotic treatment and subsequent
blood cultures showed no growth. However, due to continuing decline in kidney
function, immunosuppressive therapy was started. Despite immunosuppressive
therapy and antibiotics, renal function did not improve and chronic hemodialysis
was required. Due to rarity of condition, there are no definite treatment
guidelines available. Antibiotics, steroids, immunosuppressive agents can be of
help in most cases. Further research in this regard may help with early diagnosis
and better treatment modalities.
PMID- 29942724
TI - Role of Immune Checkpoint Inhibitors in Advanced or Recurrent Endometrial Cancer.
AB - Currently, treatment options for patients with advanced or recurrent endometrial
cancer remain limited. The current standard of care treatment for advanced
endometrial carcinoma is a platinum doublet chemotherapy. Second-line treatment
options overall are very limited. There is no optimal treatment option for
patients who show disease progression with first-line therapy. Therefore, novel
and more efficacious therapies for patients with advanced or recurrent disease
are needed. Immune checkpoint inhibitors have demonstrated a very impressive
safety profile and anti-tumor activity in patients with programmed death-ligand 1
(PD-L1) positive endometrial cancer who were pre-treated with chemotherapy. We
have done a detailed review of the literature to emphasize the role of immune
checkpoint inhibitors in the treatment of metastatic or recurrent endometrial
cancer.
PMID- 29942725
TI - Torsion of Ovarian Dysgerminoma in a Child: Role of Computed Tomography.
AB - Dysgerminomas are malignant germ cell tumors of the ovary that most commonly
occur in the adolescent population. Ovarian dysgerminoma presenting with
complications like torsion is a rare entity in the pediatric age group. Cross
sectional imaging plays a crucial role in diagnosis, tumor staging before
surgical resection, and for planning adjuvant chemotherapy. We report a case of a
nine-year-old female who presented to the emergency room (ER) with abdominal
distention and abdominal pain. Computed tomography scan revealed a large right
sided pelvic mass with areas of low attenuation, speckled calcification,
peritumoral free fluid, and a twisted vascular pedicle that was likely
originating from the left adnexa. The right ovary was normal in appearance.
Suspicion of a left-sided ovarian tumor with torsion was raised, which was later
confirmed on surgery and histopathology of the resected specimen.
PMID- 29942726
TI - Armour(r) Thyroid Rage - A Dangerous Mixture.
AB - Armour(r) Thyroid (Forest Pharmaceuticals, LLC; affiliate of Allergan, Dublin,
Ireland) is a natural porcine derivative thyroid supplement that is frequently
used without physician monitoring by health enthusiasts as a weight loss
supplement. Although there are no publications associating Armour Thyroid and
major coronary events, significant drug interactions may exist. A 32-year-old
male with a history of hypothyroidism, cystic acne, and solitary congenital
kidney presented to the emergency room after experiencing crushing substernal
chest pain radiating to his left shoulder, accompanied by diaphoresis and
shortness of breath. The patient denied any tobacco use or family history of
heart disease. He was self-administering 120 mg of Armour Thyroid daily. On
examination, the patient was well-developed with cystic acne and a flushed
appearance. His vital signs on admission were a blood pressure of 171/106 mmHg,
heart rate of 88 beats per minute (bpm), and respiratory rate of 16 breaths/min.
The electrocardiogram revealed marked ST-segment elevation in the anterior chest
leads. Laboratory studies revealed elevated troponins. Urine drug screen was
negative. The patient underwent an emergent coronary angiogram, which confirmed
an occluded left anterior descending artery. He was treated successfully by
thrombectomy and stenting of his left anterior descending artery. Evaluation for
other causes of thrombosis was negative: glycosylated hemoglobin (HbA1C) 5.5%,
low-density lipoprotein (LDL) 127 mg/dL, high-density lipoprotein (HDL) 33 mg/dL,
hypercoagulable evaluation negative, and hemoglobin (Hgb) 17.1 gm/dL. Luteinizing
hormone (LH) and follicle stimulating hormone (FSH) were < 0.20 miu/mL. Thyroid
profile results were thyroid-stimulating hormone (TSH) 0.20 miu/mL (low), T3 free
4.08 pg/mL (high), and T4 total 1.2 mcg/dL (low), which were consistent with
exogenous thyroid hormone administration. Focused questioning triggered by his
cystic acne led to the discovery that the patient was self-administering
exogenous testosterone replacement therapy. The patient declined to share
specifics with the healthcare team. This was confirmed by a high testosterone
level of 1,311 ng/dL. Hyperthyroidism increases the risk of cardiovascular events
two to three times through the propagation of a hypercoagulable, hypofibrinolytic
state possibly via an increase in clotting factors, a decrease in fibrinolytic
enzymes, and an increased inhibition of the protein C pathway. The effect of
androgens on cardiovascular mortality is uncertain. Androgens stimulate the
hemostatic system, increase adverse lipid profile, and erythropoiesis. The
combined therapy likely resulted in a synergistic potentiation of
hypercoagulable, hypofibrinolytic effects of both agents. Given the absence of
other cardiovascular risk factors, the cause of the myocardial infarction in our
patient was likely due to drug interaction between Armour Thyroid and exogenous
testosterone therapy. Due to the potential drug interaction between both natural
and prescribed thyroid hormone and testosterone supplements, patients should be
discouraged from self-administration of thyroid or anabolic steroids. Due to the
lack of standardization in the T3 content, the use of Armour Thyroid should be
avoided.
PMID- 29942727
TI - Stereotactic Radiosurgery for Prostate Cancer Following Magnetic Resonance
Imaging Directed Biopsy: A Multidisciplinary Approach with Case Examples.
AB - Classically, prostate cancer has been diagnosed via systematic, transrectal
ultrasound-guided biopsy prompted by an abnormal digital rectal exam or elevated
serum prostate-specific antigen (PSA) level. The development of multi-parametric
magnetic resonance imaging (MRI) has led to improved detection of prostate cancer
foci. For patients with clinically localized prostate cancer seeking definitive
therapy through radiation therapy, external beam radiation has been a mainstay
with a movement toward hypofractionation, notably prostate stereotactic body
radiotherapy (SBRT). We aim to describe the practical aspects of establishing a
multidisciplinary, MRI-based prostate SBRT program by means of case examples. The
prostate SBRT team at the University of Alabama at Birmingham has been performing
prostate SBRT for over four years using a multidisciplinary workflow. We have
additionally completed a phase II trial of prostate SBRT with additional
targeting of intraprostatic lesions with higher doses of radiation using a
simultaneous integrated boost technique. While there have been no reported
randomized trials of prostate SBRT, this treatment has been proven safe and
effective for properly selected patients with low and intermediate-risk prostate
cancer. We present our multidisciplinary approach to prostate SBRT with two
clinical cases targeting high-risk [MAM1] lesions in different anatomic zones of
the prostate highlighting pertinent clinical challenges in successfully
delivering prostate SBRT and managing potential side effects. In conclusion, we
report a multidisciplinary, MRI-based approach to treating patients with ultra
hyperfractionated stereotactic radiosurgery as primary definitive treatment for
prostate cancer.
PMID- 29942728
TI - A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia.
AB - We describe the case of a 53-year-old woman who visited many pneumologists
without a diagnosis until finally being diagnosed with diffuse idiopathic
pulmonary neuroendocrine cell hyperplasia (DIPNECH). It is a relatively new
disease characterized by neuroendocrine cell hyperplasia in small airways. She
has stable DIPNECH and neuroendocrine carcinoma with somatostatin therapy.
PMID- 29942729
TI - Off-label Sodium Oxybate in Childhood Narcolepsy: A Comprehensive Report.
AB - Narcolepsy is a sleep disorder that can manifest in childhood or adolescence by
causing excessive sleepiness, hallucinations, sleep attacks, or cataplexy. There
is often a significant delay in diagnosis with the mean time being 15 years from
the onset of symptoms, which may lead to further exacerbations and a high
comorbidity burden. Although narcolepsy is predominantly associated with loss of
hypocretin (orexin), the role of genetics is poorly understood and, therefore, is
complementary to the diagnosis but not confirmatory. We present the case of a
child who was misdiagnosed as suffering from schizophrenia only to later uncover
narcolepsy with cataplexy. Even though she did not meet strict criteria for
narcolepsy type 1, her history and objective data were consistent enough to make
an official diagnosis. In addition, her clinical response to treatment was very
positive, further supporting narcolepsy as the most likely underlying condition.
This presentation highlights the importance of continued education and research
to reduce the risk of delay in diagnosis or misdiagnosis.
PMID- 29942730
TI - Immunization Against Hepatitis A Virus and Hepatitis B Virus in Patients with
Chronic Liver Disease: Are We Doing a Good Job?
AB - INTRODUCTION: In the era of highly effective vaccines for Hepatitis A Virus (HAV)
and Hepatitis B Virus (HBV), acute viral hepatitis in patients with a chronic
liver disease remains a public health concern. Vaccination for HAV and HBV is
endorsed by all liver society guidelines. The aim of our study was to determine
the rates of immunization in an internal medicine resident clinic. METHODS: We
identified patients with a chronic liver disease seen at the University of
Oklahoma Internal Medicine resident clinic between June 2014 and May 2015. ICD-9
code 571 was used to identify patients with a chronic liver disease. Vaccination
records and patient data were reviewed. RESULTS: A total of 141 patients with a
chronic liver disease (mean age 54.1 years, 56% males) were identified. Almost
half of the patients (47.5%) were also being seen in the gastroenterology clinic.
During the internal medicine resident clinic visit, vaccination against HAV and
HBV was addressed for 50% and 46% of the patients, respectively. Patients being
seen by senior residents were more likely to be immunized against HAV (OR 2.7,
p=0.009) and HBV (OR 2.1, p=0.03). Patients followed in the GI clinic were more
likely to be immunized against HAV (OR 2.1, p= 0.02) and HBV (OR 2.0, p=0.02).
The gender of the treating physician and etiology had no impact on vaccination
rates. DISCUSSION: Immunization rates for HAV and HBV remain subpar despite clear
guidelines for patients with a chronic liver disease. This provides an important
avenue for improvement. Different strategies, including resident education,
developing vaccination protocols, and referral to the gastroenterology clinic,
are likely to improve vaccination status for patients with chronic liver
diseases.
PMID- 29942731
TI - Imatinib-induced Hepatitis in a Patient Treated for Gastrointestinal Stromal
Tumor: A Rare Adverse Effect.
AB - Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the digestive
tract. The clinical behavior of GISTs varies greatly, has extended follow-up, and
almost all of the tumors have malignant potential. The introduction of imatinib
has led to extraordinary improvements in the treatment of individuals with GISTs
(as well as those with Philadelphia chromosome-positive chronic myeloid leukemia
(CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL)).
However, there have been notable postmarketing reports of adverse drug reactions
of hepatotoxicity with the use of imatinib. By our search, among individuals
taking imatinib for the treatment of GIST, only six cases of drug-induced liver
injury (DILI) have been reported. Here, we present an interesting case of an
elderly woman who developed DILI after taking imatinib for the treatment of GIST.
As the liver function tests (LFTs) initially did not improve, it was decided to
proceed with an interventional radiology (IR)-guided liver biopsy, which showed a
histologic pattern of acute hepatitis, consistent with DILI. Ultimately,
discontinuation of the antineoplastic agent led to recovery in the patient's
clinical condition along with normalization of her LFTs over the next several
weeks. Thus, it is essential that physicians remain alert for and suspect DILI
for any patient being treated with imatinib who presents with a sudden elevation
of LFTs. The key to making the diagnosis is stopping the offending agent and
closely monitoring the liver enzymes for improvement. When discontinuation of
imatinib alone does not lead to improvement in LFTs and the patient's clinical
status, a detailed history should be taken and initial diagnostic testing
performed to exclude other etiologies. And, if they are negative, a liver biopsy
should be considered.
PMID- 29942732
TI - Risk-Assessment of Esophageal Surgery: Diagnosis and Treatment of Celiac Trunk
Stenosis.
AB - Anastomotic leakage of the gastric conduit following surgical treatment of
esophageal cancer is a life-threatening complication. An important risk factor
associated with anastomotic leakage is calcification of the supplying arteries of
the gastric conduit. The patency of calcified splanchnic arteries cannot be
assessed on routine computed tomography (CT) scans for esophageal cancer and, as
such, in selected patients with known or assumed mesenteric artery disease,
additional CT angiography of the abdominal arteries with 1 mm slices is strongly
encouraged. If the mesenteric perfusion is compromised in patients with
resectable esophageal cancer, angioplasty procedures with stenting of the
mesenteric arteries could be performed to prevent possible ischemia of the
gastric conduit.
PMID- 29942733
TI - Estimating lifetime and 10-year risk of lung cancer.
AB - Lung cancer is the commonest cancer worldwide. Mortality and incidence rates are
traditionally used to assess cancer burden and as public health indicators.
However, these metrics are difficult to interpret at an individual level.
Providing the lifetime and 10-year risks of cancer could improve risk
communication. Our aim was to estimate current lifetime and 10-year risks of lung
cancer by smoking status and changes in these risks between 1995 and 2013 in a
Swiss population. We used all lung cancer cases recorded between 1995 and 2013 by
two population-based cancer registries in the contiguous cantons of Vaud and
Valais, in Western Switzerland. We estimated sex-specific lifetime risk and 10
year risk of lung cancer using the current probability method, accounting for
competing risk of death. Estimates were also provided by smoking status. Between
1995 and 2013, 9623 cases of lung cancer were recorded. During this period, the
lifetime risk decreased in men from 7.1% to 6.7% and increased in women from 2.5%
to 4.1%. In both sexes, the 10-year risk of lung cancer increased with age until
the age of 60-70 and decreased thereafter. Difference in the cumulative risk
between current, former, and never smokers were very large and reported in user
friendly charts to ease risk communication. These lifetime and 10-year risk
estimates could be used systematically as public health indicators. Regularly
updating risk estimations are necessary for conditions like lung cancer whose
incidence has changed substantially.
PMID- 29942734
TI - Distal Clavicle Fracture Repair Using Cortical Button Fixation With
Coracoclavicular Ligament Reconstruction.
AB - Management of distal clavicle fractures remains controversial. Various treatment
options have been described including open reduction and internal fixation with
hook plate fixation, tension band wiring, screw fixation, and distal locking
plates. Many of these techniques are associated with a high perioperative
complication rate. We describe a surgical technique that allows indirect fixation
of distal clavicle fractures and reconstruction of the CC ligaments without the
use of prominent hardware.
PMID- 29942735
TI - Arthroscopic Untethering of the Fat Pad of the Knee: Release or Resection of the
Infrapatellar Plica (Ligamentum Mucosum) and Related Structures for Anterior Knee
Pain.
AB - Anterior knee pain (AKP), a multifactorial symptom complex, can be successfully
treated surgically. A specific diagnosis often cannot be made, but the pain is
linked to an unrecognized common factor in most patients: the mechanical behavior
of the non-isometric contents of the anterior compartment of the knee-the fat pad
(FP) and infrapatellar plica (IPP). The objective of this presentation is to
describe an effective arthroscopic technique that treats AKP by addressing this
common factor. The operation consists of release or resection of the IPP, or
ligamentum mucosum, which tethers the FP. These highly innervated tissues act
together as a hydraulic shock absorber, filling the anterior compartment. They
stretch and deform at the extremes of knee motion because of constraint centrally
by the non-isometric IPP. These dynamic changes in shape are eliminated when the
plica is released or resected. Pain perception is from perturbed nociceptive
nerves: pain relief results from de-tensioning these contained nerves by
untethering the fat pad. Ascribing pain causation is problematic because
morphologic change, such as inflammation, fibrosis, or contracture of these
structures, is only present in a minority of cases. Nonetheless, AKP is both
physically linked to these central, pain-sensitive structures and relieved by
this operation.
PMID- 29942736
TI - Pulmonary Langerhans Cell Histiocytosis(PLCH) masquerading as Atypical
Mycobacterial infection.
PMID- 29942737
TI - Incidental extensive adenocarcinoma in lungs explanted from a transplant
recipient with an idiopathic pulmonary fibrosis flare-up: A clinical dilemma.
AB - Patients under consideration for lung transplantation as treatment for end-stage
lung diseases such as idiopathic pulmonary fibrosis (IPF) often have risk factors
such as a history of smoking or concomitant emphysema, both of which can
predispose the patient to lung cancer. In fact, IPF itself increases the risk of
lung cancer development by 6.8% to 20%. Solid organ malignancy (non-skin) is an
established contraindication for lung transplantation. We encountered a clinical
dilemma in a patient who presented with an IPF flare-up and underwent urgent
evaluation for lung transplantation. After transplant, the patient's explanted
lungs showed extensive adenocarcinoma in situ, with the foci of invasion and
metastatic adenocarcinoma in N1-level lymph nodes, as well as usual interstitial
pneumonia. Retrospectively, we saw no evidence to suggest malignancy in addition
to the IPF flare-up. Clinical diagnostic dilemmas such as this emphasize the need
for new noninvasive testing that would facilitate malignancy diagnosis in
patients too sick to undergo invasive tissue biopsy for diagnosis. Careful
pathological examination of explanted lungs in patients with IPF is critical, as
it can majorly influence immunosuppressive regimens, surveillance imaging, and
overall prognosis after lung transplant.
PMID- 29942738
TI - Trypanosome co-infections increase in a declining marsupial population.
AB - Understanding the impacts of parasites on wildlife is growing in importance as
diseases pose a threat to wildlife populations. Woylie (syn. brush-tailed
bettong, Bettongia penicillata) populations have undergone enigmatic declines in
south-western Western Australia over the past decade. Trypanosomes have been
suggested as a possible factor contributing towards these declines because of
their high prevalence in the declining population. We asked whether temporal
patterns of infection with Trypanosoma spp. were associated with the decline
patterns of the host, or if other factors (host sex, body condition, co-infection
or rainfall) were more influential in predicting infection patterns. Species
specific nested PCRs were used to detect the two most common trypanosomes (T.
copemani and T. vegrandis) from 444 woylie blood samples collected between 2006
and 2012. Time relative to the decline (year) and an interaction with co
infection by the other trypanosome best explained patterns of infection for both
trypanosomes. The prevalence of single species infections for both T. copemani
and T. vegrandis was lower after the population crash, however, the occurrence of
co-infections increased after the crash compared to before the crash. Our results
suggest an interaction between the two parasites with the decline of their host,
leading to a higher level of co-infection after the decline. We discuss the
possible mechanisms that may have led to a higher level of co-infection after the
population crash, and highlight the importance of considering co-infection when
investigating the role of parasites in species declines.
PMID- 29942739
TI - Polymerase chain reaction-based open reading frame typing (POT) method analysis
for a methicillin-resistant Staphylococcus aureus (MRSA) outbreak through breast
feeding in the neonatal intensive care unit.
AB - Introduction: The route of methicillin-resistant Staphylococcus aureus (MRSA)
transmission in the neonatal intensive care unit (NICU) is not clearly explained.
We investigate an MRSA outbreak involving five babies in the NICU. The molecular
investigation using polymerase chain reaction-based open reading frame typing
(POT) method was performed. Presentation of outbreak: A MRSA outbreak occurred in
a six-bed NICU affecting 5 babies. Within 13 days of the emergence of index case,
all five babies including triplets and other two babies were found to colonize
MRSA by the active surveillance culture. Environmental surveillance cultures
revealed that the preserved breast milk provided by the triplets' mother was the
only item in the NICU that was positive for MRSA. The mother had a bite wound on
the nipples, and the breast milk was not pasteurized. The POT method revealed
that MRSA strains detected from the triplets, the breast milk, and the other baby
who was fed the triplets' mother's milk were genetically identical (POT index:
106-247-33). The all strains of MRSA carried Staphylococcal cassette chromosome
mec (SCCmec) IV and had good susceptibility for the non-beta-lactam antimicrobial
agents, suggesting the strains were community-acquired MRSA. Conclusions: The
mother's milk contaminated with community-origin MRSA is serving as the reservoir
of MRSA and one of the sources of MRSA outbreaks in the NICU. It is important to
closely monitor the condition of the mothers of the children in the NICU.
Pasteurization of breast milk should be considered when the skin on the nipple is
broken.
PMID- 29942740
TI - Talaromyces marneffei infection in a non-HIV non-endemic population.
AB - Introduction: Talaromyces marneffei infection is a systemic mycosis, caused by a
dimorphic fungus, an opportunistic pathogen formerly known as Penicillium
marneffei. This disease is endemic to Southeast Asia and common in human
immunodeficiency virus (HIV) infected patients with low CD4 counts. Here we
present a very rarely reported case of Talaromyces marneffei infection in an
apparent non-immunosuppressed patient presenting decades later in a non-endemic
setting (United States). Presentation of case: Our patient was a 75-year-old
Caucasian Navy veteran, who served in Vietnam as a part of the Swift Boat service
in 1966. He presented to his primary care provider with uncontrolled
nonproductive cough and abnormal chest computerized tomography. Bronchoscopy
specimens showed Talaromyces. He was empirically treated with itraconazole and
then switched to voriconazole after confirmation of diagnosis but he later
deteriorated was changed to liposomal amphotericin B and isavuconazole. Patient
did well for the next 90 days on isavuconazole until the therapy was stopped.
Soon after stopping the medication (isavuconazole) his symptoms recurred and
ultimately patient expired. Discussion: Talaromycosis generally presents as
pulmonary infection with manifestations similar with other endemic fungi. It is
often seen HIV patients with travel to South east Asia. Very rarely this
infection is seen and reported in non-immunosuppressed and in non-endemic areas.
To date there are 4 well-documented cases among non-HIV, non-endemic population.
Conclusion: Talaromyces can cause infection in non-HIV and non-endemic population
and could be an underrecognized cause of pulmonary infections among veterans with
even a remote history of exposure to the organism during deployment.
PMID- 29942741
TI - Anal tuberculosis: A non-Healing anal lesion.
AB - Anal tuberculosis is an extremely rare extrapulmonary presentation of
tuberculosis (TB). Less than 1% of the individuals who contract TB manifests as
gastrointestinal TB, and anoperineal TB is much less frequently encountered, 1%
of the TB cases of the digestive tract. A rare case of anal tuberculosis is
reported in a 37-year-old male patient with a recent anal fistula surgery and
relapsing anal lesions. AFB were detected by biopsy and culture. In total, the
treatment course lasted 6 months and the patient showed signs of recovery in the
early stages of the treatment (after 2 weeks), and complete remission was
achieved. In conclusion, it is recommended that in case of encountering Non
healing and recurrent anal lesions, especially in regions endemic for TB, should
be evaluated for tuberculosis.
PMID- 29942742
TI - First confirmed case of human rabies in Saudi Arabia.
AB - Rabies is an almost invariably fatal Lyssavirus-induced disease, that causes
acute encephalitis in humans and other mammals. The viral reservoirs include both
wild and domestic animals. The infection causes about 24000 to 60000 deaths
worldwide per year (Giesen et al., 2015; Naghavi et al., 2015) with Africa and
Asia having the majority of human deaths (95%) caused by rabies. Rabies is
endemic in animals in Arabian peninsula. Some countries in the region such as
Saudi Arabia, Yemen and Oman are reporting increasing number of cases of wildlife
rabies. Among these countries Saudi Arabia is largest, but published data
regarding the rabies status in the country are scarce. We report a case of a 60
year old Saudi man who was admitted to cardiac ICU of a tertiary care hospital in
Makkah, primarily with history of chest pain for cardiac evaluation, who was
found to have signs suggestive hydrophobia. On history, it was found that he had
an unprovoked scratch on his face by a dog in Morocco a month prior to admission
and his saliva PCR test confirmed rabies virus.
PMID- 29942743
TI - Subclinical leprosy manifesting as a reversal reaction after LHRH agonist
administration.
PMID- 29942744
TI - An unusual odontogenic infection due to Clostridium subterminale in an
immunocompetent patient: A case report and review of the literature.
AB - Clostridium subterminale is an anaerobic spore-forming bacterium usually
associated with infections in patients who are immunocompromised. This case
report focuses on a rare presentation of a multifascial space odontogenic
infection associated with the bacterial isolate Clostridium subterminale. The
management of an odontogenic infection associated with an isolate of Clostridium
subterminale in an immunocompetent female is described, as well as a review of
the literature.
PMID- 29942745
TI - A case of acute disseminated encephalomyelitis following Mycoplasma pneumoniae
infection.
AB - We report a case of acute disseminated encephalomyelitis (ADEM) secondary to
Mycoplasma pneumoniae infection that failed to improve with methylprednisolone
and intravenous immunoglobulin (IVIG); who responded with plasmapheresis. A 21-
year- old female with an unremarkable medical history, initially presented to an
outside hospital with fever and an influenza-like illness and was subsequently
intubated for worsening sensorium. Brain magnetic resonance imaging was
suggestive of ADEM or vasculitis for which she received five days of pulse
steroids and IVIG. She showed no signs of improvement and was transferred to our
hospital for plasmapheresis. Her work up revealed an elevated IgM antibody and
positive sputum for Mycoplasma pneumonia by polymerase chain reaction, suggesting
the pathogen as the culprit for her ADEM. Intravenous azithromycin and daily
plasmapheresis were initiated for seven consecutive days. Following commencement
of her treatment, the patient experienced good recovery and was subsequently
extubated. She continued to improve with physical therapy and gained mobility,
with the help of a walker. Patients commonly present with ADEM following viral
infection or vaccination and less frequently post bacterial infection. The
current treatment of ADEM due to Mycoplasma pneumoniae is based on limited case
reports. Our patient poorly responded to pulse steroids and IVIG, while she
markedly improved on azithromycin and plasmapheresis. In patients presenting with
encephalopathic signs and neurological manifestations following pneumonia;
Mycoplasma pneumoniae infection and subsequent immune-mediated demyelination
should be considered.
PMID- 29942746
TI - Incidental diagnosis of sternoclavicular septic arthritis with Moraxella
nonliquefaciens.
AB - An 83-year old man presented acutely to the emergency department with generalized
weakness and subjective fevers. A month earlier he had undergone resection of a
large intramuscular sarcoma from his thigh. The cancer staging work-up was still
underway and a decision about adjuvant therapy was still pending. Although
initial laboratory assessment showed leukocytosis, this normalized soon after
admission without the use of antimicrobials. No fevers were documented. During
the admission an 18F-FDG PET/CT was performed in continuation of his sarcoma
staging workup. This revealed unexpected abnormal radiotracer uptake in the left
sternoclavicular joint with fluid collections extending into the
sternocleidomastoid muscle and the mediastinum. Imaging findings were consistent
with septic arthritis and abscess formation, despite lack of fever or localizing
symptoms. Ultrasound-guided aspiration revealed purulent fluid that grew
Moraxella nonliquefaciens. Given the unusual presentation, ongoing clinical
uncertainty about the true cause of the septic joint, and concern for an occult
sarcoma metastasis, surgical debridement and resection of the joint was carried
out. Pathology and microbiology evaluation confirmed septic arthritis with
osteomyelitis and abscess extension into the mediastinum. No tumor cells were
identified. Postoperative course was complicated by hematoma, but otherwise the
patient responded well to antimicrobial therapy.
PMID- 29942747
TI - Adult onset immunoglobulin A vasculitis (Henoch-Schonlein purpura) with alveolar
hemorrhage.
AB - S. pyogenes is the cause of many important human diseases, ranging from mild
superficial skin infections to life-threatening systemic diseases. The post
streptococcal syndromes are immune mediated phenomena including Immunoglobulin A
Vasculitis (Henoch-Schonlein purpura). HSP is more common in children and usually
self limited but it can cause skin, joint, renal, gastrointestinal and rarely
respiratory involvement. We present a case with Streptococcus pyogenes pneumonia
that presented with respiratory failure, pulmonary hemorrhage, extensive rash and
renal failure.
PMID- 29942748
TI - Salmonella Enteritidis cholecystitis with chronic granulomatous disease.
AB - We describe a 40-year-old woman with Salmonella cholecystitis complicating adult
onset X-linked chronic granulomatous disease (CGD) caused by a de novo mutation
in the paternal-origin CYBB gene. CGD was diagnosed by familial genetic analysis
of the CYBB gene encoding NADPH oxidase gp91phox after detection of a refractory
subcutaneous abscess at the age of 28. At age 40, she began experiencing frequent
fever and diarrhea over a period of 3 months that were refractory to
antibacterial treatment. Cholecystitis was evident. Her symptoms improved after
percutaneous trans-hepatic gallbladder aspiration puncture with stand-by
cholecystectomy. Salmonella enterica serotype Enteritidis (S. Enteritidis) was
detected in blood, stool, and bile acid samples. Due to her suppressed
bactericidal ability caused by CGD, S. Enteritidis was considered to have
translocated from the gut to reside in the gallbladder, causing her repeated
enteritis and sepsis. When encountering CGD with recurrent salmonellosis, the
possibility of cholecystitis should be considered as another infection focus.
PMID- 29942749
TI - Pericarditis due to Neisseria meningitidis serogroup W135.
AB - Neisseria meningitidis is a well-recognized cause of bacterial meningitis.
Although less common, N. meningitidis can also involve extra-meningeal sites,
including the pericardium. The frequency of such extra-meningeal clinical
manifestations differs depending on N. meningitidis serogroup. N. meningitidis
serogroups C and W135 have been reportedly associated with extra-meningeal
meningococcal disease more frequently including pericarditis. In general,
meningococcal pericarditis is categorized into three etiologies; primary
meningococcal disease, secondary disease due to disseminated meningococcemia, and
reactive form as an immunologic complication. Importantly, meningococcal
pericarditis can cause massive pericardial effusion with cardiac tamponade that
can lead to cardiogenic shock. We report a case of pericarditis due to N.
meningitidis serogroup W135 secondary to disseminated meningococcal disease.
PMID- 29942750
TI - Cellulitis and Bacteremia due to Neisseria weaveri following a dog bite.
AB - Neisseria weaveri is a gram-negative rod that can cause skin and soft tissue
infections associated with dog bites. Although N. weaveri is a less well
recognized zoonotic Neisseria species, its potential pathogenicity merits
recognition since N. weaveri can cause severe septicemia in humans.
PMID- 29942751
TI - A lost world disease: Copra itch outbreak caused by Tyrophagus longior mite.
AB - An outbreak investigation of copra itch revealed a cluster of six suspected cases
with skin dermatitis, with 11-32 years of age, belonging to a single family,
between June and July 2016 in Phang Nga province, Southern Thailand.
Epidemiologic investigation of these suspected cases revealed five probable cases
developing multiple discrete erythematous papules with intense pruritus on the
body rather than the extremities and one confirmed case whose skin was infested
with domestic mite, Tyrophagus longior (Gervais) (Ascari: Ascaridae). This mite
was also found in unused coir mattresses outside their bedrooms. Household
infestation with T. longior mites rendered these family members to become more
susceptible to expose indoor biting of T. longior adult mites that were adapted
well to the domestic environments with poor hygienic conditions. Human exposure
to mite bites was more likely to be a direct contact than an indirect contact.
Findings from this copra itch outbreak investigation provided understanding of
natural disease of copra itch and factors that favored the outbreak, and could
guide diagnosis for physicians, surveillance and response for surveillance and
rapid response teams (SRRTs), and prevention and control for entomologists and
public health personnel.
PMID- 29942752
TI - Multiple gas emboli complicating an emphysematous pyelonephritis.
AB - We report a rare case of emphysematous pyelonephritis complicated by septic shock
and multiple gas emboli in the pulmonary artery (with transient cor pulmonale),
coronary artery (with transient acute coronary syndrome).
PMID- 29942753
TI - Necrotizing osteomyelitis in a man with disseminated Mycobacterium chelonae
infection.
AB - Cases of disseminated nontuberculous mycobacterial (NTM) infection are difficult
to treat. We encountered an elderly man with disseminated Mycobacterium chelonae
infection. The clinical evaluation and treatment of patients with this type of
systemic infection pose unique challenges. Disseminated NTM infection with bone
involvement often requires surgical intervention in addition to antimicrobial
therapy.
PMID- 29942754
TI - Sloughing skin in intravenous drug user.
AB - A 32 year old female, an active intravenous drug user, was admitted for fever,
myalgias and an erythematous macular rash on her distal extremities. She quickly
decompensated and developed septic shock. Her examination was significant for a
progressive rash which within two days developed bullae and necrosis with
progression to a confluent rash involving her palms and soles (Figs. 1 and 2).
Her rash involved nearly one third of her body with what was equivalent to a
third degree burn. Her labs were significant for leukocytosis with bandemia,
elevated liver function tests with worsening thrombocytopenia and fibrinogen
levels consistent with disseminated intravascular coagulation (DIC) Her
transthoracic echocardiogram (Fig. 3) showed a 5 cm vegetation on the tricuspid
valve. Her blood cultures were positive for methicillin-sensitive Staphylococcus
aureus. She was meeting the clinical criteria for toxic shock syndrome (TSS) and
subsequent testing for toxic shock syndrome toxin antibody was positive. She was
treated with antibiotics and intravenous gamma globulin (IVIG). Due to her
worsening rash she was transferred to a burns unit. She was diagnosed with
Purpura fulminans (PF) which is a skin manifestation of DIC and has a rare
association with Staphylococcus aureus infection.The main focus of this case
report is to emphasise this rare association, prompt an early diagnosis and
referral to prevent life threatening complications.
PMID- 29942755
TI - Fatal breakthrough mucormycosis in a multivisceral transplant patient receiving
micafungin: Case report and literature review.
AB - Introduction: Antifungal agents are routinely used in the post-transplant setting
for both prophylaxis and treatment of presumed and proven fungal infections.
Micafungin is an echinocandin-class antifungal with broad antifungal cover and
favorable side effect profile but, notably, it has no activity against molds of
the order Mucorales. Presentation of case: A 47-year-old woman underwent
multivisceral transplantation for intestinal failure-associated liver disease.
She had a prolonged post-operative recovery complicated by invasive candidiasis
and developed an intolerance to liposomal amphotericin B. In view of her
immunosuppression, she was commenced on micafungin as prophylaxis to prevent
invasive fungal infection. However, she developed acute graft versus host disease
with bone marrow failure complicated by disseminated mucormycosis which was only
diagnosed post mortem. Discussion: Non-Aspergillus breakthrough mold infections
with micafungin therapy are rare with only eight other cases having been
described in the literature. Breakthrough infections have occurred within one
week of starting micafungin. Diagnosis is problematic and requires a high degree
of clinical suspicion and microscopic/histological examination of an involved
site. The management of these aggressive infections involves extensive
debridement and appropriate antifungal cover. Conclusion: A high level of
suspicion of invasive fungal infection is required at all times in
immunosuppressed patients, even those receiving antifungal prophylaxis. Early
biopsy is required. Even with early recognition and aggressive treatment of these
infections, prognosis is poor.
PMID- 29942756
TI - Multiple recurrent abscesses in a patient with undiagnosed IL-12 deficiency and
infection by Burkholderia gladioli.
AB - We report the occurrence of two severe illnesses experienced by one patient over
a 19 year period of time. Both illnesses were characterized by severe
inflammation and tissue destruction. Signs and symptoms of the first illness were
characteristic of lymphogranuloma venereum (LGV). The second illness mimicked
scrofula. During the second illness the patient was discovered to have a rare
immunodeficiency due to auto-antibodies to Interleukin (IL)-12 and infection by
Burkholderia gladioli, a plant pathogen usually harmless in humans. We were able
to retrieve biopsies from the first illness to establish that B. gladioli was
already present during the original presentation. That first illness lasted 5
year s, but she survived without the correct pathogen ever being identified, and
without a diagnosis of immunodeficiency. After a remission of 10 year s, she
experienced her second illness. The responses to treatment before and after the
correct diagnoses were established provide us with an excellent opportunity to
consider and discuss how disease expression reflects complex relationships
between host defenses and microbial characteristics.
PMID- 29942757
TI - First confirmed case of Powassan neuroinvasive disease in Rhode Island.
AB - The Powassan Virus is the arthropod-borne vector responsible for Powassan
neuroinvasive disease. The virus was first isolated in 1958 and has been
responsible for approximately 100 cases of neuroinvasive disease. Rates of
infection have been on the rise over the past decade with numerous states
reporting their first confirmed case; New Jersey, New Hampshire and Connecticut
all reported their first case within the last five years. We present here the
first confirmed case of Powassan neuroinvasive disease in the nearby state of
Rhode Island. A previously healthy 81-year-old female with known tick exposure
presented with fever, altered sensorium, seizures and focal neurological
deficits. After an extensive work-up that was largely unrevealing Powassan
encephalitis was suspected. The diagnosis was confirmed with serological testing
consisting of Powassan IgM enzyme-linked immunosorbent assay and Powassan plaque
reduction neutralization testing. The case study provides evidence for the
increasing spread of Powassan neuroinvasive disease and reinforces the importance
of requesting focused testing for Powassan Virus in patients from an endemic area
with a clinically compatible syndrome.
PMID- 29942758
TI - Pulmonary artery intravascular abscess: A rare complication of incomplete
infective endocarditis treatment in the setting of injection drug use.
AB - Infective endocarditis (IE) is a serious complication of injection drug use.
Right-sided IE encompasses 5-10% of all IE cases, with the majority involving the
tricuspid valve (TV). The predominant causal organism is Staphylococcus aureus.
Most cases of right-sided IE can be successfully treated with antimicrobials, but
approximately 5-16% require eventual surgical intervention. We report the case of
a 36-year-old female with active injection drug use who developed methicillin
sensitive Staphylococcus aureus IE of the tricuspid valve. Associated with poor
adherence to medical therapy as a consequence of opioid addiction, she developed
septic emboli to the lungs and an intravascular abscess in the left main
pulmonary artery. These long-term potentially fatal, sequelae of incompletely
treated IE require surgical intervention, as medical therapy is unlikely to be
sufficient. Surgical management may involve TV replacement, pulmonary artery
resection, and pneumonectomy. Prevention of these complications may have been
achieved by concurrent opioid addiction therapy. An intravascular pulmonary
artery abscess is a novel complication of advanced IE that has not been
previously reported. This complication likely arose due to incomplete IE
treatment as a consequence of opioid addiction, highlighting the need for
concurrent addiction management. Intravenous antimicrobial therapy is likely not
adequate, and surgical intervention, including pulmonary artery resection and
pneumonectomy may be necessary.
PMID- 29942759
TI - Cave diving for a diagnosis: Disseminated histoplasmosis in the
immunocompromised.
AB - Tumor necrosis factor (TNF) inhibitors are widely used in the treatment of
inflammatory conditions and are associated with risks of invasive infections. We
present a diagnostically challenging patient with unique comorbidities and travel
history. A 53-year-old man with a history of polysubstance abuse and psoriasis on
adalimumab presented to our hospital directly from the airport with fever,
dyspnea, and cough. He had been living in Costa Rica and engaged in many outdoor
activities. Within 6 hours and a limited history, he was intubated; vasopressors
and antimicrobials were promptly administered. An extensive infectious disease
investigation was undertaken, considering potential travel-related exposures and
his immunosuppressive state. However, multi-organ failure with worsening
disseminated intravascular coagulation ensued, and within four days of admission,
the patient passed away. Five days after his death, the urine Histoplasma antigen
resulted positive. Disseminated histoplasmosis should be suspected in a patient
on anti-TNF therapy, with a severe febrile illness and pneumonia refractory to
antibacterial therapy. A high index of suspicion is necessary to make the
diagnosis and initiate prompt treatment.
PMID- 29942760
TI - Lawsonella clevelandensis as the causative agent of a breast abscess.
AB - Lawsonella clevelandensis is a Gram-stain-positive, partially acid-fast,
anaerobic, being considered a new species within a new genus in the suborder
Corynebacterineae. There are only a few cases reported worldwide. This is a
fastidious microorganism, difficult to identify by conventional methods, leading
to inappropriate treatments. The authors report a case of a 29-year-old woman
with a 3-week evolution of a breast nodule. There was a family history of breast
carcinoma. Samples were collected for histological and microbiological
examination. Gram staining revealed Gram-positive filamentous bacilli, acid-fast
positive. The cultural examination revealed a Lawsonella clevelandensis that was
confirmed by molecular methods. At the last follow up, the evolution was
favorable; the abscess was resolved, with no evidence of recurrence. To our
knowledge the present case was the first reported in Europe.
PMID- 29942761
TI - Gastric syphilis: The great imitator in the stomach.
AB - Syphilis is resurging worldwide. Here, we present the case of a 33-year-old
heterosexual man who presented with a 3-week history of epigastric pain, nausea,
emesis, and 8 kg weight loss. He was subsequently diagnosed with gastric
syphilis, based on reactive syphilis serological testing and Treponema pallidum
found in gastric biopsy specimens. Gastric syphilis is a rare presentation
observed in 1% of cases and usually develops in secondary syphilis. Given the
nonspecific manifestation and findings, a high index of suspicion is required for
diagnosis of gastric syphilis.
PMID- 29942762
TI - A malar rash from inner Rio de Janeiro State, Brazil.
AB - A 49-year-old previously healthy woman from Rio de Janeiro State, Brazil,
presented with a right malar rash that started as a tiny pustule and progressed
to an ulcerated papulonodular lesion within ten weeks. A presumptive diagnosis of
zoonotic sporotrichosis was made based on excellent response to treatment and
epidemiological linkage with a diseased cat.
PMID- 29942763
TI - An uncommon complication of Listeria monocytogenes infection:
Polyradiculoneuritis following Listeria meningoencephalitis.
AB - Listeria monocytogenes, primarily a foodborne pathogen, is commonly responsible
for disorders affecting the central nervous system and cranial nerves. We hereby
present the first case to our knowledge of listeriosis linked to a peripheral
neurological disorder causing acute upper limb weakness.
PMID- 29942764
TI - Fatal pancytopenia due to albendazole treatment for strongyloidiasis.
AB - We report 7 cases of strongyloidiasis that had occurred from 2016 through 2017 in
a tertiary hospital of southern China. Three of the 7 patients (age 66-77) with
farming exposure many years ago developed symptomatic infection while receiving
immunosuppressant for underlying medical conditions. The majority of them were
treated with albendazole due to unavailability of ivermectin in mainland China.
One of the 7 patients, with underlying IgG4 sclerosing cholangitis and secondary
biliary cirrhosis was on immunosuppressives and developed severe pancytopenia 15
days after albendazole treatment. He ultimately died of polymicrobial sepsis.
This was the second fatal case being reported in the literature as a consequence
of albendazole-induced myelosuppression. We have undertaken a review of the
literature regarding the use of albendazole for strongyloidiasis and its adverse
effect with a focus on myelosuppression as a rare but potentially serious event.
PMID- 29942765
TI - Lyme disease presenting with multiple cranial neuropathies on MRI.
AB - We present the case of a 10-year old patient from southeastern Ontario with
severe bilateral facial palsy. MRI was performed that showed extensive symmetric
enhancement of cervical cranial nerve roots and multiple cranial nerves (III, V,
VI, VII, VIII, X and XII). Lumbar puncture was performed that revealed
pleocytosis and elevated proteins in the cerebrospinal fluid. Serology confirmed
the diagnosis of neuroborreliosis. The patient was treated with a 4-week course
of IV ceftriaxone, following which he returned to baseline.
PMID- 29942766
TI - New technology meets clinical knowledge: Diagnosing Streptococcus suis meningitis
in a 67-year-old man.
AB - Strepotocuccus suis (S. suis) infection is known to be caused by the exposure to
contaminated animals, specifically pigs and wild boars. This pathogen can cause
bacterial meningitis, and one report indicated that it is the most common
pathogen causing bacterial meningitis in Vietnam (Mai et al., 2008). A 67-year
old man was diagnosed with S. suis bacteremia and meningitis. In general,
identification of this pathogen using standard biochemical methods takes time. We
successfully diagnosed S. suis bacteremia in this patient, however, using the
relatively new technology called Matrix-Assisted Laser Desorption/Ionization Time
of-Flight mass spectrometry (MALDI-TOF MS). Knowledge of the characteristics of
S. suis and this newer technology led to the definitive diagnosis and prompt
management of this patient. Herein, we highlight the use of a new technology in
the context of sound microbiological knowledge in caring for patients.
PMID- 29942767
TI - Out of town guest: A healthy 7 year old from a non-endemic area presents with
histoplasmosis granulomatous disease.
AB - Histoplasmosis is a common fungal infection, normally infecting people exposed to
demolition sites or bat/bird droppings in the central and eastern states. When a
child presents with a chest mass and eosinophilia in a non-endemic region the
likelihood of an infectious process like pulmonary histoplasmosis is unknown. A
seven year old immunocompetent child with a mediastinal mass and eosinophilia
presented with acute cough, fever, non-bloody emesis, and four pound weight loss.
A neoplastic work up was negative. Further evaluation showed a positive M band
(chronic histoplasmosis infection) and negative H band (acute infection). Tissue
obtained by thoracotomy demonstrated necrotizing granulomatous inflammation with
calcification consistent with histoplasmosis. Patient recovered after completion
of a twelve week course of itraconazole. A mediastinal mass in a symptomatic
child has a 50% risk of cancer as the primary diagnosis. The Infectious Disease
Society of America guidelines recommend treatment of histoplasmosis granulomatous
disease with itraconazole if symptomatic and surgery only for obstruction. Thus
our patient did not have a clear indication for surgery. In a child with a
mediastinal mass, despite low risk factors should they be evaluated for a fungal
infection prior to invasive surgery? This case demonstrates that histoplasmosis
can cause a granuloma in a non-endemic region and that an infectious etiology
ought to be considered when working up a symptomatic child with a chest mass as
it may prevent unnecessary surgery.
PMID- 29942768
TI - Late onset acute pancreatitis in P. falciparum malaria - An adverse reaction to
intravenous artesunate?
PMID- 29942769
TI - Infective endocarditis associated with Bartonella henselae: A case series.
AB - Organisms in the genus Bartonella are cause of blood culture-negative
endocarditis. Bartonella infective endocarditis is being increasingly reported
worldwide; however, reports from Japan are limited. Here, we report five cases of
infective endocarditis associated with Bartonella henselae. All patients had a
history of contact with cats or fleas; this information helped achieve an
appropriate diagnosis.
PMID- 29942770
TI - Bullous and pustular cutaneous larva migrans: two case reports and a literature
review.
AB - Cutaneous larva migrans (CLM) is a common skin infestation in tropical countries.
The classic presentation is a serpiginous, migratory track on the feet. Local and
systemic reactions, as well as secondary bacterial infections, are rarely
reported. The authors report two cases of CLM with a blister and pustular
response on uncommon body locations. The patients were treated with anthelmintic
therapy, and a topical corticosteroid was used to relieve their severe reactions.
This report aims to describe an infrequent presentation of a common disease and
review treatment plans.
PMID- 29942771
TI - Gemella haemolysans bacteremia in a patient with secondary peritonitis due to a
duodenal ulcer perforation: A case report.
AB - We describe a case of Gemella haemolysans septic shock in a 75-year old Japanese
male with a duodenal perforation and secondary peritonitis. Blood cultures on
admission were positive for Gram-positive and Gram-variable cocci, and G.
haemolysans was identified using whole cell matrix-assisted laser
desorpition/ionization mass spectrometry (MALDI-TOF MS), with a score value of
2.12. The 16S rRNA sequencing was difficult to use as a diagnostic test because
there was more than 99% sequence homology with related bacterial strains. Based
on both the biochemical profiles and whole groEL sequence, we concluded that the
strain in our patient was G. haemolysans. The patient was successfully treated
with a 16-day course of antimicrobials. His clinical condition improved, and no
evidence of a relapse of the infection was noted. Although MALDI-TOF MS and 16S
rRNA sequencing are useful for identification of the species, the basic
biochemical profile is also important to identify a rare species.
PMID- 29942772
TI - A case of Pasteurella multocida pneumonia needed to differentiate from non
tuberculous mycobacteriosis.
AB - We report a case of Pasteurella multocida pneumonia. A 71-year old Japanese woman
with pulmonary infiltration of the lingual division of left lung 3 years before,
which was thought to be caused by non-tuberculous mycobacteriosis (NTM) was
referred to our clinic on account of chronic cough, sputum, dyspnea, and left
pulmonary infiltration. Although she owned over 10 cats, no bites or scratches
were mentioned. Pasteurella multocida was confirmed by the culture of the
patient's bronchoalveolar lavage (BAL) fluid. NTM infection was ruled out by acid
fast bacillus smears, cultures, and polymerase chain reaction of three sputum
specimens and BAL fluid. The infection route in this case was considered to have
resulted from inhalation of contaminated aerosols or contact with her cats. Close
contact with animals should be avoided, particularly for patients with chronic
pulmonary diseases, as it is a risk factor for pneumonia due to Pasteurella
multocida.
PMID- 29942773
TI - Shewanella cellulitis and bacteremia following marine water exposure.
PMID- 29942774
TI - Cryptococcosis as a cause of nephrotic syndrome? A case report and review of the
literature.
AB - We present a case of a 74 years old male with cutaneous cryptococcosis of the
right forearm. Cryptococcus neoformans var. neoformans was cultivated from the
skin and from the bloodstream. He was diagnosed with nephrotic syndrome (focal
segmental glomerulosclerosis) 21 months prior to admission, which was steroid
dependent. He was treated with prednisone and cyclosporine A. Concurrently with
his renal disease he was also diagnosed as having disseminated severe tinea
mannum, tinea corporis and tinea cruris; onychomycosis, skin eczema and
psoriasis. After a prolonged course of anti-fungal therapy, his skin lesions as
well as his nephrotic syndrome recovered completely. Follow up after 7 months
without any anti-fungal or immunosuppression showed no skin or renal recurrence.
We assume that the renal disease was related to the pre-existing cutaneous
cryptococcosis, aggravated by immunosuppression, and discuss the close
association between cutaneous cryptococcosis and nephrotic syndrome, as well as
similar case reports in the literature.
PMID- 29942775
TI - Fourier's gangrene associated with a decubitus ulcer.
PMID- 29942776
TI - Fatal spotted fever rickettsiosis in Argentina.
AB - We present a fatal case of a 17-year-old male patient who was hospitalized for
febrile seizures and generalized skin rash.
PMID- 29942777
TI - A rare case of influenza A in a hospitalized adult presenting with encephalitis
and a seizure.
AB - Influenza A in hospitalized adults uncommonly may present with neurologic
manifestations, e.g., encephalitis. Encephalitis is the most common influenza
related neurologic complication in adults, However, seizures in hospitalized
adults due to influenza are extremely rare. This is a case of a 58 year old
female hospitalized for influenza A. On admission, she was confused and obtunded.
Her EEG showed diffuse global slowing indicative of encephalitis. On hospital day
(HD) #2, she had a seizure. She had no history of a seizure disorder, and was not
febrile at the time of the seizure. While seizures are not uncommon in children
(febrile seizures) with influenza B, but in adults with influenza A, only a few
cases of seizures have been reported. This case was most interesting in having
both encephalitis and seizure complicating influenza A. If present,
neuropsychiatric manifestations may be due to ostelamivir, but encephalitis and
seizures are not among the neurologic adverse effects of ostelamivir. In adults
hospitalized with influenza A, clinicians should be alert to the possibility of
neurologic complications.
PMID- 29942778
TI - Comment on "Mycobacterium neoaurum line-related bacteremia with pulmonary
involvement: Case report and review of literature''.
PMID- 29942779
TI - The diagnosis of symptomatic acute antiretroviral syndrome during the window
period with antigen/antibody testing and HIV viral load.
AB - Despite much focus on moving toward a cure to end the epidemic human
immunodeficiency virus (HIV) epidemic there are still thousands of new infections
occurring every year in the United States. Although there is ongoing transmission
of HIV in the United States and a growing population of people living with HIV,
the acute presentation of HIV infection can be challenging to diagnose and is
often not considered when patients present to healthcare providers. Although in
certain states there are HIV testing laws that require that all persons between
the ages of 13 and 64 be offered HIV testing in an opt-out approach, many patient
presenting with an acute illness, that would warrant diagnostic testing for HIV,
leave without having an HIV test performed for either diagnostic or screening
purposes. We describe the case of a woman who presented to medical attention with
symptoms later confirmed to be due to acute HIV infection. She was initially
discharged from the hospital and only underwent HIV testing with confirmation of
her diagnosis after readmission. We describe the algorithm where fourth
generation testing combined with HIV viral load testing allowed for the diagnosis
of acute HIV prior to the development of a specific immunoglobulin response.
Consideration of this diagnosis, improved HIV screening, and understanding of the
use of antigen/antibody screening tests, combined with Multispot and HIV viral
RNA detection, when appropriate, can allow for early diagnosis of HIV before
progression of disease and before undiagnosed patient spread the infection to new
contacts.
PMID- 29942780
TI - Group A streptococcus acute otitis media progressing to neuroinvasive disease in
adults.
AB - Acute otitis media affects 700 million people each year with children being
disproportionately affected relative to adults. Group A streptococcus is a
pathogen implicated in a broad array of human pathology. It is, however, a rare
cause of acute otitis media and neuroinvasive disease in older adults with only 2
3 cases occurring per year in the United States. We describe two such cases from
a single institution in Rhode Island in 2017. The clinical presentation,
neuroimaging and management are reviewed. The mechanism of intracranial spread
may have involved dehiscence of the bony tegmen of the roof of the middle ear
cavity.
PMID- 29942781
TI - A case of cutaneous metastasis mimicking herpes zoster rash.
AB - Cutaneous metastasis is a rare occurrence and often is confused with infectious
etiology most commonly herpes zoster rash. We present a case 49 year old male
with history of metastatic colon cancer with persistent dermatomal vesicular rash
that thought to be due to herpes zoster. A skin biopsy eventually revealed
malignant cells.
PMID- 29942782
TI - Comment on: Disseminated Nocardia cyriacigeorgia causing pancreatitis in a
haploidentical stem cell transplant recipient.
PMID- 29942783
TI - Letter to the editor - Nocardia identification.
PMID- 29942784
TI - A case of chronic granulomatous craniofacial osteomyelitis.
AB - We present the clinical image of a 56-year old male who presented with chronic
multiple craniofacial discharging sinuses with lytic, sclerotic destruction of
facial bones on radiology causing gross facial deformity. He remained undiagnosed
for years. The diagnosis was clinched on histopathology as a chronic
granulomatous osteomyelitis showing Actinomyces.
PMID- 29942785
TI - Bezold's abscess in a diabetic patient without significant clinical symptoms.
AB - A 52-year-old Japanese man with a history of type 2 diabetes mellitus (DM)
presented with mild dizziness. On admission, the physical examination only
revealed tachycardia and right sided cervical lymphadenopathy. On the fifth day
of admission, his mental status slightly worsened. Urgent Computed Tomography
(CT) of the head and neck revealed multiple abscesses spreading from the right
temporal bone to the right sternocleidomastoid muscle. Bezold's abscess was
diagnosed. Streptococcus pneumoniae was isolated from middle ear fluid and blood
cultures. Bezold's abscess has rarely been described in the era of antimicrobial
therapy. However this abscess can still occur in patients without any typical
severe symptoms. Repeated history taking and thorough physical examination can
help detect Bezold's abscess.
PMID- 29942786
TI - Toxocariasis of the eye.
PMID- 29942787
TI - Secondary immune thrombocytopenia (ITP) as an initial presentation of Whipple's
disease.
AB - Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease characterized
by low platelet count that has been associated with a number of chronic
infections but rarely described as a manifestation of Whipple's disease (WD). We
present a case of Whipple's disease in a patient initially diagnosed with ITP. A
46-year old male in the fifth decade of life presented with presumed idiopathic
ITP and was treated with several therapies including corticosteroids, rituximab,
and thrombopoietin receptor agonists. Several years later, he developed weight
loss and worsening arthralgias. He was found to have evidence of WD in a jejunal
lymph node, the duodenum, and the cerebral spinal fluid (CSF). His diagnosis of
WD, as a cause of secondary ITP, came a full 8 years after he was discovered to
have thrombocytopenia and over 4 years after he was diagnosed with ITP. WD is an
uncommon, multiorgan system disease caused by the actinomycete Tropheryma
whipplei. Whipple's disease presents a diagnostic challenge due to the wide array
of possible presenting clinical manifestations, as well as a prolonged time
course with separation of symptoms over many years. While T. whipplei is
ubiquitous in the environment, few individuals develop clinical disease, raising
the prospect that select immunodeficiencies, both singular or in combination, may
play a role in infection. While rare, in the appropriate clinical setting, one
should consider infection with T. whipplei in addition to other chronic
infections as a cause of secondary ITP regardless of how long ago the diagnosis
of ITP was made.
PMID- 29942788
TI - A rare case of giant renal angiomyolipoma in a woman with tuberous sclerosis.
PMID- 29942789
TI - A narrative review on do's and don'ts in prescription label writing - lessons for
pharmacists.
AB - Providing medicines information is a key role of a pharmacist. Miscommunication
between pharmacist and patient may lead to adverse drug events or therapeutic
failure. The aim of the review was to summarize the available research findings
on factors that lead to poor communication between pharmacist and patient when
providing written medicines information on dispensing and auxiliary labels and
identify successful interventional approaches that help to alleviate these
concerns. We selected articles available on PubMed, SAGE, and Google Scholar
databases that are relevant to our objective. A total of 33 articles that matched
the objectives of this review were retrieved and evaluated by all three authors.
It was found that patient literacy levels, number of medicines dispensed, format
and organization of the label, complexity of dosing instructions, precision of
writing dosing instructions and use of icons, graphics and pictograms were
aspects that were frequently used, and hence assessed by research groups on
medicine label writing. Most studies reported that simple and straight forward
instructions written legibly were better comprehended by patients. Based on our
findings, we provide here useful tips for pharmacists on writing dosing
instructions for patients. Finally, we spotlight crucial research gaps related to
communicating written dosing instructions that need to be addressed in the
future.
PMID- 29942790
TI - Pharmacist-led screening in sexually transmitted infections: current
perspectives.
AB - Introduction: Sexually transmitted infection (STI) screening is a crucial
initiative that aims to reduce the increasing global prevalence of many common
STIs such as chlamydia, gonorrhea, and herpes simplex virus (HSV). Many STIs are
either asymptomatic or show mild symptoms that are often attributed to other
infections; hence, screening is the only way to identify - and by extension,
treat - them. In this way, the spread of STIs can be reduced, and the health
implications of an untreated STI are minimized. Community pharmacies could
provide an avenue to convenient, confidential STI screening by using noninvasive
or minimally invasive sample collection techniques that are used by the consumer
or pharmacist. We identified the most common STIs found globally and investigated
the current and potential role of pharmacists in provision of STI screening
interventions. Discussion: There is sufficient evidence for pharmacy-based
chlamydia screening, with many consumers and pharmacists finding it an acceptable
and highly valued service. Some evidence was found for pharmacy-based gonorrhea,
hepatitis B virus (HBV), and human immunodeficiency virus (HIV) screening.
Appropriate sample collection for gonorrhea screening needs to be further
examined in a pharmacy setting. HBV screening presented an increased risk of
personal injury to pharmacists through the collection of whole blood specimens,
which could be reduced through consumer self-sampling. Pharmacist-collected
specimens for HIV is less risky as an oral swab can be used, nullifying the risk
of transmission; but pre- and post-screen consultations can be time-intensive;
hence, pharmacists would require remuneration to provide an ongoing HIV screening
service. Not enough evidence was found for syphilis screening through community
pharmacies; more studies are required that consider sampling methods other than
pharmacist-collected whole blood specimens. There is no evidence to date for
pharmacist-led trichomoniasis or HSV screening. Conclusion: Pharmacists are well
positioned to provide STI screening services, but further investigations are
needed to overcome financial, safety, and confidentiality barriers.
PMID- 29942791
TI - An Extended Hypofractionated Palliative Radiotherapy Regimen for Head and Neck
Carcinomas.
AB - Background: Palliative radiotherapy to patients with head and neck cancer is
often necessary, but there is a substantial variation in the treatment regimens
reported in the literature, and consensus on the most appropriate schedules does
not exist. In order to minimize acute toxicity while at the same time trying to
achieve prolonged tumor control, a long hypofractionated regimen has been used
routinely in Denmark. In the current retrospective study, we investigated the
outcome in patients intended for palliative radiotherapy with this regimen.
Materials and methods: Patients with newly diagnosed head and neck cancer treated
with palliative radiotherapy of 52-56 Gy in 13-14 fractions twice weekly from
2009 to 2014 were included. Patients were excluded if they had previously
received radiotherapy. Data on disease location, stage, patient performance
status (PS), treatment response, acute skin and mucosal toxicity, and late
fibrosis were collected prospectively and supplemented with information from
medical records. Results: 77 patients were included in the study. Fifty-eight
patients (75%) completed the intended treatment. Loco-regional tumor response
(complete or partial) was evaluated 2 months posttreatment and observed in 45% of
the entire population corresponding to 71% of patients alive. PS had a
significant influence on survival (p = 0.007) and on not completing the intended
treatment. Grade III or IV acute mucositis were observed in 25%, and grade III or
IV acute dermatitis observed in 15%. Conclusion: Palliative hypofractionated
radiotherapy with 52-56 Gy in 13-14 fractions shows good tumor response and
tolerability in a vulnerable patient population. However, it may not be suited
for patients in poor PS.
PMID- 29942792
TI - A Review of Circulating Tumor DNA in Hepatobiliary Malignancies.
AB - Circulating tumor DNA (ctDNA) is released into circulation (blood) specifically
from tumor cells undergoing metabolic secretion, apoptosis, or necrosis, carries
tumor-specific genetic or epigenetic alterations. Technologies enabling clinical
evaluation of ctDNA continue to advance rapidly and allow for the assessment of
patient-specific tumoral genetic and epigenetic alterations. This holds great
potential for earlier detection of disease, serial monitoring of tumor
heterogeneity, identification of therapeutic targets, and evaluation of treatment
response and mechanisms of resistance. Hepatobiliary malignancies are often
diagnosed late, recur commonly, yield limited available tumor on biopsy, and
harbor several genomic alterations with potential therapeutic impacts. Patients
suffering from or at risk for these diseases thus stand to benefit immensely from
this technology. Herein, we review the limited literature pertaining to the
potential for ctDNA technologies in such patients. Patients with these cancers
stand to benefit greatly from the application of ctDNA technologies, and
concerted efforts at further investigation of such are ongoing and greatly
needed.
PMID- 29942793
TI - Blood Serum From Head and Neck Squamous Cell Carcinoma Patients Induces Altered
MicroRNA and Target Gene Expression Profile in Treated Cells.
AB - The head and neck squamous cell carcinoma (HNSCC) represents one of the most
common cancers in humans. Close to 600,000 new diagnoses are made every year
worldwide and over half of diagnosed patients will not survive. In view of this
low survival rate, the development of novel cell-based assays for HNSCC will
allow more mechanistic approaches for specific diagnostics for each individual
patient. The cell-based assays will provide more informative data predicting
cellular processes in treated patient, which in effect would improve patient
follow up. More importantly, it will increase the specificity and effectiveness
of therapeutic approaches. In this study, we investigated the role of serum from
HNSCC patients on the regulation of microRNA (miRNA) expression in exposed cells
in vitro. Next-generation sequencing of miRNA revealed that serum from HNSCC
patients induced a different miRNA expression profile than the serum from healthy
individuals. Out of 377 miRNA detected, we found that 16 miRNAs were
differentially expressed when comparing cells exposed to serum from HNSCC or
healthy individuals. The analysis of gene ontologies and pathway analysis
revealed that these miRNA target genes were involved in biological cancer-related
processes, including cell cycle and apoptosis. The real-time PCR analysis
revealed that serum from HNSCC patients downregulate the expression level of five
genes involved in carcinogenesis and two of these genes-P53 and SLC2A1-are direct
targets of detected miRNAs. These novel findings provide new insight into how
cancer-associated factors in circulation regulate the expression of genes and
regulatory elements in distal cells in favor of tumorigenesis. This has the
potential for new therapeutic approaches and more specific diagnostics with tumor
specific cell lines or single-cell in vitro assays for personalized treatment and
early detection of primary tumors or metastasis.
PMID- 29942794
TI - MuvB: A Key to Cell Cycle Control in Ovarian Cancer.
AB - Cancer cells are characterized by uncontrolled proliferation, whereas the ability
to enter quiescence or dormancy is important for cancer cell survival and disease
recurrence. Therefore, understanding the mechanisms regulating cell cycle
progression and exit is essential for improving patient outcomes. The MuvB
complex of five proteins (LIN9, LIN37, LIN52, RBBP4, and LIN54), also known as
LINC (LIN complex), is important for coordinated cell cycle gene expression. By
participating in the formation of three distinct transcriptional regulatory
complexes, including DREAM (DP, RB-like, E2F, and MuvB), MMB (Myb-MuvB), and
FoxM1-MuvB, MuvB represents a unique regulator mediating either transcriptional
activation (during S-G2 phases) or repression (during quiescence). With no known
enzymatic activities in any of the MuvB-associated complexes, studies have
focused on the therapeutic potential of protein kinases responsible for
initiating DREAM assembly or downstream enzymatic targets of MMB. Furthermore,
the mechanisms governing the formation and activity of each complex (DREAM, MMB,
or FoxM1-MuvB) may have important consequences for therapeutic response. The MMB
complex is associated with prognostic markers of aggressiveness in several
cancers, whereas the DREAM complex is tied to disease recurrence through its role
in maintaining quiescence. Here, we review recent developments in our
understanding of MuvB function in the context of cancer. We specifically
highlight the rationale for additional investigation of MuvB in high-grade serous
ovarian cancer and the need for further translational research.
PMID- 29942795
TI - Prognostic Role of Hypoxia-Inducible Factor-2alpha Tumor Cell Expression in
Cancer Patients: A Meta-Analysis.
AB - Hypoxia-inducible factor-2alpha (HIF-2alpha) plays an important role in tumor
progression and metastasis. A number of studies have evaluated the correlation
between HIF-2alpha overexpression and clinical outcome in cancer patients but
yielded inconsistent results. To comprehensively and quantitatively summarize the
evidence on the capability of HIF-2alpha to predict the prognosis of cancer
patients with solid tumors, a meta-analysis was carried out. Renal cell carcinoma
(CC-RCC) was separately analyzed due to an alternative mechanism of regulation.
Systematic literature searches were performed in PubMed and Embase databases for
relevant original articles until February 2018. Forty-nine studies with 6,052
patients were included in this study. The pooled hazard ratios (HRs) with
corresponding confidence intervals were calculated to assess the prognostic value
of HIF-2alpha protein expression in tumor cells. The meta-analysis revealed
strong significant negative associations between HIF-2alpha expression and five
endpoints: overall survival [HR = 1.69, 95% confidence interval (95% CI) 1.39
2.06], disease-free survival (HR = 1.87, 95% CI 1.2-2.92), disease-specific
survival (HR = 1.57, 95% CI 1.06-2.34), metastasis-free survival (HR = 2.67, 95%
CI 1.32-5.38), and progression-free survival (HR = 2.18, 95% CI 1.25-3.78).
Subgroup analyses revealed similar associations in the majority of tumor sites.
Overall, these data demonstrate a negative prognostic role of HIF-2alpha in
patients suffering from different types of solid tumors.
PMID- 29942797
TI - Correction to: Molecular, biochemical and kinetic analysis of a novel,
thermostable lipase (LipSm) from Stenotrophomonas maltophilia Psi-1, the first
member of a new bacterial lipase family (XIX).
AB - [This corrects the article DOI: 10.1186/s40709-018-0074-6.].
PMID- 29942796
TI - High Throughput Screening for Natural Host Defense Peptide-Inducing Compounds as
Novel Alternatives to Antibiotics.
AB - A rise in antimicrobial resistance demands novel alternatives to antimicrobials
for disease control and prevention. As an important component of innate immunity,
host defense peptides (HDPs) are capable of killing a broad spectrum of pathogens
and modulating a range of host immune responses. Enhancing the synthesis of
endogenous HDPs has emerged as a novel host-directed antimicrobial therapeutic
strategy. To facilitate the identification of natural products with a strong
capacity to induce HDP synthesis, a stable macrophage cell line expressing a
luciferase reporter gene driven by a 2-Kb avian beta-defensin 9 (AvBD9) gene
promoter was constructed through lentiviral transduction and puromycin selection.
A high throughput screening assay was subsequently developed using the stable
reporter cell line to screen a library of 584 natural products. A total of 21
compounds with a minimum Z-score of 2.0 were identified. Secondary screening in
chicken HTC macrophages and jejunal explants further validated most compounds
with a potent HDP-inducing activity in a dose-dependent manner. A follow-up oral
administration of a lead natural compound, wortmannin, confirmed its capacity to
enhance the AvBD9 gene expression in the duodenum of chickens. Besides AvBD9,
most other chicken HDP genes were also induced by wortmannin. Additionally,
butyrate was also found to synergize with wortmannin and several other newly
identified compounds in AvBD9 induction in HTC cells. Furthermore, wortmannin
acted synergistically with butyrate in augmenting the antibacterial activity of
chicken monocytes. Therefore, these natural HDP-inducing products may have the
potential to be developed individually or in combinations as novel antibiotic
alternatives for disease control and prevention in poultry and possibly other
animal species including humans.
PMID- 29942798
TI - Cortical microtubule orientation in Arabidopsis thaliana root meristematic zone
depends on cell division and requires severing by katanin.
AB - Background: Transverse cortical microtubule orientation, critical for anisotropic
cell expansion, is established in the meristematic root zone. Intending to
elucidate the possible prerequisites for this establishment and factors that are
involved, microtubule organization was studied in roots of Arabidopsis thaliana,
wild-type and the p60-katanin mutants fra2, ktn1-2 and lue1. Transverse cortical
microtubule orientation in the meristematic root zone has proven to persist under
several regimes inhibiting root elongation. This persistence was attributed to
the constant moderate elongation of meristematic cells, prior to mitotic
division. Therefore, A. thaliana wild-type seedlings were treated with
aphidicolin, in order to prevent mitosis and inhibit premitotic cell elongation.
Results: In roots treated with aphidicolin for 12 h, cell divisions still
occurred and microtubules were transverse. After 24 and 48 h of treatment,
meristematic cell divisions and the prerequisite elongation ceased, while
microtubule orientation became random. In meristematic cells of the p60-katanin
mutants, apart from a general transverse microtubule pattern, cortical
microtubules with random orientation were observed, also converging at several
cortical sites, in contrast to the uniform transverse pattern of wild-type cells.
Conclusion: Taken together, these observations reveal that transverse cortical
microtubule orientation in the meristematic zone of A. thaliana root is cell
division-dependent and requires severing by katanin.
PMID- 29942800
TI - Best Practices for Developing and Validating Scales for Health, Social, and
Behavioral Research: A Primer.
AB - Scale development and validation are critical to much of the work in the health,
social, and behavioral sciences. However, the constellation of techniques
required for scale development and evaluation can be onerous, jargon-filled,
unfamiliar, and resource-intensive. Further, it is often not a part of graduate
training. Therefore, our goal was to concisely review the process of scale
development in as straightforward a manner as possible, both to facilitate the
development of new, valid, and reliable scales, and to help improve existing
ones. To do this, we have created a primer for best practices for scale
development in measuring complex phenomena. This is not a systematic review, but
rather the amalgamation of technical literature and lessons learned from our
experiences spent creating or adapting a number of scales over the past several
decades. We identified three phases that span nine steps. In the first phase,
items are generated and the validity of their content is assessed. In the second
phase, the scale is constructed. Steps in scale construction include pre-testing
the questions, administering the survey, reducing the number of items, and
understanding how many factors the scale captures. In the third phase, scale
evaluation, the number of dimensions is tested, reliability is tested, and
validity is assessed. We have also added examples of best practices to each step.
In sum, this primer will equip both scientists and practitioners to understand
the ontology and methodology of scale development and validation, thereby
facilitating the advancement of our understanding of a range of health, social,
and behavioral outcomes.
PMID- 29942799
TI - Current understanding of reovirus oncolysis mechanisms.
AB - Mammalian orthoreovirus (reovirus) is under development as a cancer virotherapy.
Clinical trials demonstrate that reovirus-based therapies are safe and tolerated
in patients with a wide variety of cancers. Although reovirus monotherapy has
proven largely ineffective, reovirus sensitizes cancer cells to existing
chemotherapeutic agents and radiation. Clinical trials are underway to test the
efficacy of reovirus in combination with chemotherapeutic and radiation regimens
and to evaluate the effectiveness of reovirus in conjunction with
immunotherapies. Central to the use of reovirus to treat cancer is its capacity
to directly kill cancer cells and alter the cellular environment to augment other
therapies. Apoptotic cell death is a prominent mechanism of reovirus cancer cell
killing. However, reoviruses can also kill cancer cells through nonapoptotic
mechanisms. Here, we describe mechanisms of reovirus cancer cell killing,
highlight how reovirus is used in combination with existing cancer treatments,
and discuss what is known as to how reovirus modulates cancer immunotherapy.
PMID- 29942801
TI - Changes in Protein O-GlcNAcylation During Mouse Epididymal Sperm Maturation.
AB - After leaving the testis, sperm undergo two sequential maturational processes
before acquiring fertilizing capacity: sperm maturation in the male epididymis,
and sperm capacitation in the female reproductive tract. During their transit
through the epididymis, sperm experience several maturational changes; the
acquisition of motility is one of them. The molecular basis of the regulation of
this process is still not fully understood. Sperm are both transcriptionally and
translationally silent, therefore post-translational modifications are essential
to regulate their function. The post-translational modification by the addition
of O-linked beta-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of
phosphorylation in different cellular processes. Therefore, our work was aimed to
characterize the O-GlcNAcylation system in the male reproductive tract and the
occurrence of this phenomenon during sperm maturation. Our results indicate that
O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is
present in the testis, epididymis and immature caput sperm. Its presence is
significantly reduced in mature cauda sperm. Consistently, caput sperm display
high levels of O-GlcNAcylation when compared to mature cauda sperm, where it is
mostly absent. Our results indicate that the modulation of O-GlcNAcylation takes
place during sperm maturation and suggest a role for this post-translational
modification in this process.
PMID- 29942804
TI - Editorial: Contemporary Strategies in the Management of Civilian Vascular Trauma.
PMID- 29942802
TI - Molecular and Cellular Mechanisms for Proteinuria in Minimal Change Disease.
AB - Minimal Change Disease (MCD) is a clinical condition characterized by acute
nephrotic syndrome, no evident renal lesions at histology and good response to
steroids. However, frequent recurrence of the disease requires additional
therapies associated with steroids. Such multi-drug dependence and frequent
relapses may cause disease evolution to focal and segmental glomerulosclerosis
(FSGS) over time. The differences between the two conditions are not well
defined, since molecular mechanisms may be shared by the two diseases. In some
cases, genetic analysis can make it possible to distinguish MCD from FSGS;
however, there are cases of overlap. Several hypotheses on mechanisms underlying
MCD and potential molecular triggers have been proposed. Most studies were
conducted on animal models of proteinuria that partially mimic MCD and may be
useful to study glomerulosclerosis evolution; however, they do not demonstrate a
clear-cut separation between MCD and FSGS. Puromycin Aminonucleoside and
Adriamycin nephrosis are models of glomerular oxidative damage, characterized by
loss of glomerular basement membrane polyanions resembling MCD at the onset and,
at more advanced stages, by glomerulosclerosis resembling FSGS. Also Buffalo/Mna
rats present initial lesions of MCD, subsequently evolving to FSGS; this
mechanism of renal damage is clearer since this rat strain inherits the unique
characteristic of overexpressing Th2 cytokines. In Lipopolysaccharide
nephropathy, an immunological condition of renal toxicity linked to B7-1(CD80),
mice develop transient proteinuria that lasts a few days. Overall, animal models
are useful and necessary considering that they reproduce the evolution from MCD
to FSGS that is, in part, due to persistence of proteinuria. The role of
T/Treg/Bcells on human MCD has been discussed. Many cytokines, immunomodulatory
mechanisms, and several molecules have been defined as a specific cause of
proteinuria. However, the hypothesis of a single cell subset or molecule as cause
of MCD is not supported by research and an interactive process seems more
logical. The implication or interactive role of oxidants, Th2 cytokines, Th17,
Tregs, B7-1(CD80), CD40/CD40L, c-Mip, TNF, uPA/suPAR, Angiopoietin-like 4 still
awaits a definitive confirmation. Whole genome sequencing studies could help to
define specific genetic features that justify a definition of MCD as a "clinical
pathology-genetic entity."
PMID- 29942803
TI - The Laboratory-Based Intermountain Validated Exacerbation (LIVE) Score Identifies
Chronic Obstructive Pulmonary Disease Patients at High Mortality Risk.
AB - Background: Identifying COPD patients at high risk for mortality or healthcare
utilization remains a challenge. A robust system for identifying high-risk COPD
patients using Electronic Health Record (EHR) data would empower targeting
interventions aimed at ensuring guideline compliance and multimorbidity
management. The purpose of this study was to empirically derive, validate, and
characterize subgroups of COPD patients based on routinely collected clinical
data widely available within the EHR. Methods: Cluster analysis was used in 5,006
patients with COPD at Intermountain to identify clusters based on a large
collection of clinical variables. Recursive Partitioning (RP) was then used to
determine a preferred tree that assigned patients to clusters based on a
parsimonious variable subset. The mortality, COPD exacerbations, and comorbidity
profile of the identified groups were examined. The findings were validated in an
independent Intermountain cohort and in external cohorts from the United States
Veterans Affairs (VA) and University of Chicago Medicine systems. Measurements
and Main Results: The RP algorithm identified five LIVE Scores based on
laboratory values: albumin, creatinine, chloride, potassium, and hemoglobin. The
groups were characterized by increasing risk of mortality. The lowest risk, LIVE
Score 5 had 8% 4-year mortality vs. 56% in the highest risk LIVE Score 1 (p <
0.001). These findings were validated in the VA cohort (n = 83,134), an expanded
Intermountain cohort (n = 48,871) and in the University of Chicago system (n =
3,236). Higher mortality groups also had higher COPD exacerbation rates and
comorbidity rates. Conclusions: In large clinical datasets across different
organizations, the LIVE Score utilizes existing laboratory data for COPD
patients, and may be used to stratify risk for mortality and COPD exacerbations.
PMID- 29942805
TI - Are Amyloid Fibrils RNA-Traps? A Molecular Dynamics Perspective.
AB - The self-assembly of proteins and peptides into amyloids is a key feature of an
increasing number of diseases. Amyloid fibrils display a unique surface
reactivity endowing the sequestration of molecules such as MicroRNAs, which can
be the active moiety of the toxic action. To test this hypothesis we studied the
recognition between a model RNA and two different steric zipper spines using
molecular dynamics simulations. We found that the interaction occurs and displays
peptide-sequence dependence. Interestingly, interactions with polar zipper
surfaces such as the formed by SNQNNF are more stable and favor the formation of
beta-barrel like complexes resembling the structures of toxic oligomers. These
sequence-structure-recognition relationships of the two different assemblies may
be exploited for the design of compounds targeting the fibers or competing with
RNA-amyloid attachment.
PMID- 29942806
TI - Development of a Contractile Cardiac Fiber From Pluripotent Stem Cell Derived
Cardiomyocytes.
AB - Stem cell therapy has the potential to regenerate cardiac function after
myocardial infarction. In this study, we sought to examine if fibrin microthread
technology could be leveraged to develop a contractile fiber from human
pluripotent stem cell derived cardiomyocytes (hPS-CM). hPS-CM seeded onto fibrin
microthreads were able to adhere to the microthread and began to contract seven
days after initial seeding. A digital speckle tracking algorithm was applied to
high speed video data (>60 fps) to determine contraction behaviour including beat
frequency, average and maximum contractile strain, and the principal angle of
contraction of hPS-CM contracting on the microthreads over 21 days. At day 7,
cells seeded on tissue culture plastic beat at 0.83 +/- 0.25 beats/sec with an
average contractile strain of 4.23+/-0.23%, which was significantly different
from a beat frequency of 1.11 +/- 0.45 beats/sec and an average contractile
strain of 3.08+/-0.19% at day 21 (n = 18, p < 0.05). hPS-CM seeded on
microthreads beat at 0.84 +/- 0.15 beats/sec with an average contractile strain
of 3.56+/-0.22%, which significantly increased to 1.03 +/- 0.19 beats/sec and
4.47+/-0.29%, respectively, at 21 days (n = 18, p < 0.05). At day 7, 27% of the
cells had a principle angle of contraction within 20 degrees of the microthread,
whereas at day 21, 65% of hPS-CM were contracting within 20 degrees of the
microthread (n = 17). Utilizing high speed calcium transient data (>300 fps) of
Fluo-4AM loaded hPS-CM seeded microthreads, conduction velocities significantly
increased from 3.69 +/- 1.76 cm/s at day 7 to 24.26 +/- 8.42 cm/s at day 21 (n =
5-6, p < 0.05). hPS-CM seeded microthreads exhibited positive expression for
connexin 43, a gap junction protein, between cells. These data suggest that the
fibrin microthread is a suitable scaffold for hPS-CM attachment and contraction.
In addition, extended culture allows cells to contract in the direction of the
thread, suggesting alignment of the cells in the microthread direction.
PMID- 29942808
TI - Assessment of Canine Autologous Conditioned PlasmaTM Cellular and Transforming
Growth Factor-beta1 Content.
AB - To evaluate (1) the cellular composition of canine ACPTM including using two
different preparation protocols with variations on centrifugation time, (2) the
effect of different activation protocols on the transforming growth factor (TGF)
beta1 content in the ACP, and (3) patient factors that might influence platelet
concentration of the ACP. ACP was made with blood from 15 dogs using a
manufacturer-recommended protocol. Each ACP sample was divided into three
aliquots that were activated with calcium chloride (CaCl2), human gamma-thrombin
(HGT), or not activated. TGF-beta1 was quantified in each aliquot using an ELISA
and comparisons among activation protocols were performed using a Skillings-Mack
test. Correlations between platelet and TGF-beta1 concentration were assessed
with a Pearson correlation coefficient. ACP was subsequently prepared from an
additional 17 dogs using a slightly modified centrifugation protocol and cellular
composition was assessed. Effects of dog age, body weight, and hematocrit were
assessed for their potential impact on ACP platelet concentration using a
multiple linear regression analysis. The mean increase in platelet concentration
in the ACP above that in the whole blood was 1.2* (+/-std 0.62) and leukocyte
concentration was a mean of 26% (0.37) that in the whole blood using the standard
protocol. There was a significant (p < 0.01) effect of activation on TGF-beta1
concentrations with mean concentrations of 4,538 (2,317), 14,948 (13,784), and
14,096 (15,210) pg/ml in aliquots that were not activated or were activated with
thrombin or CaCl2 respectively. There were significant correlations between the
platelet concentration and TGF-beta1 concentration in aliquots that were
activated with either thrombin (r = 0.66; p < 0.01) or CaCl2 (r = 0.86, p <
0.0001). The mean increase in platelet concentration was 1.4* (0.62) and the
leukocyte concentration was 0.28* (0.13) that in whole blood using the modified
ACP preparation protocol. Dog age, body weight, and hematocrit were not
significant predictors of ACP platelet concentration. These data show that on
average this preparation protocol produces a mildly platelet-concentrated,
leukoreduced platelet-rich plasma. Intentional activation had a significant
effect on TGF-beta1 concentrations with use of both CaCl2 and thrombin resulting
in higher TGF-beta1 concentrations than that obtained in samples that are not
activated.
PMID- 29942809
TI - Editorial: Digital Transformation of Animal Health Data: Proceedings of the AHEAD
2017 Workshop.
PMID- 29942807
TI - Kruppel-Like Factors in Metabolic Homeostasis and Cardiometabolic Disease.
AB - Members of the Kruppel-like factor (KLF) family of transcription factors, which
are characterized by the presence of three conserved Cys2/His2 zinc-fingers in
their C-terminal domains, control a wide variety of biological processes. In
particular, recent studies have revealed that KLFs play diverse and essential
roles in the control of metabolism at the cellular, tissue and systemic levels.
In both liver and skeletal muscle, KLFs control glucose, lipid and amino acid
metabolism so as to coordinate systemic metabolism in the steady state and in the
face of metabolic stresses, such as fasting. The functions of KLFs within
metabolic tissues are also important contributors to the responses to injury and
inflammation within those tissues. KLFs also control the function of immune
cells, such as macrophages, which are involved in the inflammatory processes
underlying both cardiovascular and metabolic diseases. This review focuses mainly
on the physiological and pathological functions of KLFs in the liver and skeletal
muscle. The involvement of KLFs in inflammation in these tissues is also
summarized. We then discuss the implications of KLFs' control of metabolism and
inflammation in cardiometabolic diseases.
PMID- 29942810
TI - Defining and Clarifying the Terms Canine Possessive Aggression and Resource
Guarding: A Study of Expert Opinion.
AB - The terms possessive aggression and resource guarding are often used
interchangeably to describe behavior patterns used by a dog to control primary
access to a perceived valuable item. The use of inconsistent terminology may
impact the effectiveness of communication between dog owners and clinicians,
affect treatment and management success for the behavior, and inhibit research
progress. The aim of this study was to explore the opinions of canine behavior
experts on the meaning of and preference for the terms possessive aggression and
resource guarding, as well as to develop and propose an operational ethological
definition for the preferential term identified. Eighty-five individuals met the
inclusion criteria and were invited to participate in a two-stage online survey.
Results from the two-stage survey found that the majority of participants
preferred the term resource guarding. Detailed exploration of meaning and
definitions required in-depth discussion beyond traditional survey methods,
therefore, respondents from the second stage of the survey were invited to
participate in an online discussion board. Following content analysis of the data
from the discussion board, we conclude that the majority of participants
preferred the term resource guarding. Considering 100% consensus was not reached
regarding terminology among experts in the field, future authors and clinicians
should provide clear definitions where terms are applied to ensure effective
communication between all parties and to ensure consistency in canine behavior
research. Based on expert contributions, we define resource guarding as "the use
of avoidance, threatening, or aggressive behaviors by a dog to retain control of
food or non-food items in the presence of a person or other animal."
PMID- 29942811
TI - International Survey Regarding the Use of Rehabilitation Modalities in Horses.
AB - To define which biologic, electrophysical and other modalities are used in horses
for injury or performance issues, a questionnaire regarding 38 modalities was
distributed to eight veterinary groups. A total of 305 complete or partial
responses were obtained from over 10 geographic regions; 75.4% from private
equine practice or regional private equine referral hospitals, 14.1% from
university teaching hospitals or satellite clinics, 8.2% from private mixed
animal practice, and 2.3% from veterinary rehabilitation centers. The majority of
respondents were located in the USA (60%), Europe (25.6%), and Canada (5.6%).
Respondents reported working with athletic horses primarily in the disciplines of
hunter-jumper (26.9%), dressage (16.0%), and pleasure riding (14.7%), followed by
Western riding, track racing, and eventing. Warmbloods (39.7%) were the
predominant breed presenting to respondents, followed by Thoroughbreds (20.3%)
and Quarter Horses (17.3%) ahead of other breeds. All 38 modalities were used by
respondents. The 10 most prominently utilized were controlled hand walking
(97.3%), therapeutic shoeing (96.1%), ice (95.2%), compression bandaging (89.5%),
platelet rich plasma (PRP; 86.5%), therapeutic exercises (84.3%), interleukin-1
receptor antagonist protein therapy (IRAP; 81.4%), stretching (83.3%), and cold
water hydrotherapy (82.9%). Heat (77.6%), massage (69.0%), and acupuncture
(68.3%) were also commonly utilized. The least prominently used modalities were
hyperbaric oxygen therapy (9.4%), cytowave (8.3%), and radiofrequency (6.4%).
Injectable modalities (IRAP, PRP, mesotherapy, stem cells) were almost solely
administered by veterinarians; other modalities were variably applied by
veterinarians, technicians, veterinary assistants, farriers, physical therapists,
trainers, and other entities. A total of 33% of respondents reported working
collaboratively with physical therapists on equine patients. Findings indicate
that a broad range of invasive and non-invasive modalities are used in equine
patients to address a variety of rehabilitation and performance needs, and that
personnel with varying levels of expertise are involved in their administration.
This suggests that further investigation to better define the delivery, efficacy
and any negative effects of many of these modalities is important.
PMID- 29942812
TI - A retrospective cohort study to compare post-injury admissions for infectious
diseases in burn patients, non-burn trauma patients and uninjured people.
AB - Background: Injury triggers a range of systemic effects including inflammation
and immune responses. This study aimed to compare infectious disease admissions
after burn and other types of injury using linked hospital admissions data.
Methods: A retrospective longitudinal study using linked health data of all
patients admitted with burns in Western Australia (n = 30,997), 1980-2012, and
age and gender frequency matched cohorts of people with non-burn trauma (n =
28,647) and no injury admissions (n = 123,399). Analyses included direct
standardisation, negative binomial regression and Cox proportional hazards
regression. Results: Annual age-standardised infectious disease admission rates
were highest for the burn cohort, followed by the non-burn trauma and uninjured
cohorts. Age-standardised admission rates by decade showed different patterns
across major categories of infectious diseases, with the lower respiratory and
skin and soft tissue infections the most common for those with burns and other
open trauma. Compared with the uninjured, those with burns had twice the
admission rate for infectious disease after discharge (incident rate ratio (IRR),
95% confidence interval (CI): 2.04, 1.98-2.11) while non-burn trauma experienced
1.74 times higher rates (95%CI: 1.68-1.81). The burn cohort experienced 10%
higher rates of first-time admissions after discharge when compared with the non
burn trauma (hazard ratio (HR), 95%CI: 1.10, 1.05-1.15). Compared with the
uninjured cohort, incident admissions were highest during the first 30 days after
discharge for burns (HR, 95%CI: 5.18, 4.15-6.48) and non-burn trauma (HR, 95%CI:
5.06, 4.03-6.34). While incident rates remained high over the study period, the
magnitude decreased with increasing time from discharge: burn vs uninjured: HR,
95%CI: 30 days to 1 year: 1.69, 1.53-1.87; 1 to 10 years: 1.40, 1.33-1.47; 10
years to end of study period: 1.16, 1.08-1.24; non-burn trauma vs uninjured: HR,
95%CI: 30 days to 1 year: 1.71, 1.55-1.90; 1 to 10 years: 1.30, 1.24-1.37; 10
years to end of study period: 1.09, 1.03-1.17). Conclusions: Burns and non-burn
trauma patients had higher admission rates for infectious diseases compared with
age and gender matched uninjured people. The pattern of annual admission rates
for major categories of infectious diseases varied across injury groups. Overall,
the burn cohort experienced the highest rates for digestive, lower respiratory
and skin and soft tissue infections. These results suggest long-term
vulnerability to infectious disease after injury, possibly related to long-term
immune dysfunction.
PMID- 29942813
TI - The venous ulcer continues to be a clinical challenge: an update.
AB - Venous ulcers are a common chronic problem in many countries especially in
Northern Europe and USA. The overall prevalence of this condition is 1% rising to
3% in the over 65 years of age. Over the last 25 years, there have been many
developments applicable to its diagnosis and treatment. These advances,
notwithstanding healing response and recurrence, are variable, and the venous
ulcer continues to be a clinical challenge. The pathogenesis of venous ulcers is
unrelieved or ambulatory venous hypertension resulting mostly from deep venous
thrombosis leading to venous incompetence, lipodermatosclerosis, leucocyte
plugging of the capillaries, tissue hypoxia and microvascular dysfunction. It is
not known what initiates venous ulcers. Triggers vary from trauma of the lower
extremity to scratching to relieve itchy skin over the ankle region. Venous
ulcers can be painful, and this condition presents an increasing burden of care.
A systematic analysis of the role of technology used for diagnosis and management
strongly supports the use of compression as a mainstay of standardised care. It
further shows good evidence for the potential of some treatment procedures to
accelerate healing. This article reviews the pathogenetic mechanisms, current
diagnostic methods and standard care and its limitations.
PMID- 29942814
TI - Clinical Outcomes After the Nonoperative Management of Lateral Patellar
Dislocations: A Systematic Review.
AB - Background: The first-line treatment for patellar dislocations is often
nonoperative and consists of physical therapy and immobilization techniques, with
various adjuncts employed. However, the outcomes of nonoperative therapy are
poorly described, and there is a lack of quality evidence to define the optimal
intervention. Purpose: To perform a comprehensive review of the literature and
assess the quality of studies presenting patient outcomes from nonoperative
interventions for patellar dislocations. Study Design: Systematic review; Level
of evidence, 4. Methods: The MEDLINE, AMED, Embase, CINAHL, Cochrane Library,
PEDro, and SPORTDiscus electronic databases were searched through July 2017 by 3
independent reviewers. The PRISMA (Preferred Reporting Items for Systematic
Reviews and Meta-Analyses) guidelines were followed. Study quality was assessed
using the CONSORT (Consolidated Standards for Reporting Trials) criteria for
randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies
and case series. Results: A total of 25 studies met our inclusion criteria,
including 12 randomized controlled trials, 7 cohort studies, and 6 case series,
consisting of 1066 patients. Studies were grouped according to 4 broad categories
of nonoperative interventions based on immobilization, weightbearing status,
quadriceps exercise type, and alternative therapies. The most commonly used
outcome measure was the Kujala score, and the pooled redislocation rate was 31%.
Conclusion: This systematic review found that patient-reported outcomes
consistently improved after all methods of treatment but did not return to
normal. Redislocation rates were high and close to the redislocation rates
reported in natural history studies. There is a lack of quality evidence to
advocate the use of any particular nonoperative technique for the treatment of
patellar dislocations.
PMID- 29942815
TI - Outcomes of Joint Preservation Procedures for Cartilage Injuries in the Hip: A
Systematic Review and Meta-analysis.
AB - Background: The detection and management of chondral injuries of the hip,
especially in a younger patient population, may preempt joint degeneration.
Although the outcomes of preservation techniques have been well described for
other weightbearing joints, such as the knee, evidence for hip joint preservation
after procedures such as microfracture and autologous chondrocyte implantation
remains in its infancy. Purpose: To evaluate outcomes of joint preservation
procedures in the hip, including the success rate and patient-reported outcomes
(PROs). Study Design: Systematic review; Level of evidence, 4. Methods: This
review was performed using the terms "hip arthroscopy," "microfracture,"
"autologous chondrocyte implantation," "fibrin glue," "osteochondral transfer,"
and variations thereof in 5 electronic databases, yielding 325 abstracts. After
the application of eligibility criteria, 19 articles were included. Weighted
means were calculated for PROs, and pooled estimates were calculated for age,
follow-up, chondral lesion size, and success of hip preservation procedures with
a random-effects proportion meta-analysis. Results: A total of 1484 patients
(1502 hips) were identified across 19 studies (mean age, 38.0 +/- 1.3 years; mean
follow-up, 31.8 +/- 9.6 months). Hip joint preservation techniques demonstrated a
high success rate, ranging from 85.6% to 99.7%. The mean pooled chondral lesion
size was 2.5 +/- 0.3 cm2 (95% CI, 1.9-3.0 cm2). Microfracture was the most
frequent technique, utilized by 11 studies, and demonstrated an 89.6% success
rate (95% CI, 82.4%-96.7%). The highest pooled success rate was exhibited by
autologous membrane-induced chondrogenesis in 3 studies (99.7% [95% CI, 99.0%
100.0%]). All PROs demonstrated a statistically significant increase
postoperatively, including the modified Harris Hip Score, Nonarthritic Hip Score,
and Hip Outcome Score-Activities of Daily Living and Hip Outcome Score-Sports
Specific Subscale (all P < .05). The visual analog scale for pain also
demonstrated a statistically significant decrease of 37.2% (P < .05). Conclusion:
Hip preservation procedures demonstrate a high success rate, with microfracture
representing the most frequently utilized cartilage preservation technique in the
peer-reviewed literature. PROs significantly improved after surgery. Further
investigation of hip preservation modalities with long-term follow-up is required
to create evidence-based clinical recommendations and treatment algorithms.
PMID- 29942817
TI - Optical coherence tomography for ocular surface and corneal diseases: a review.
AB - The advent of optical coherence tomography (OCT) imaging has changed the way
ophthalmologists image the ocular surface and anterior segment of the eye. Its
ability to obtain dynamic, high and ultra-high resolution, cross-sectional images
of the ocular surface and anterior segment in a noninvasive and rapid manner
allows for ease of use. In this review, we focus on the use of anterior segment
OCT, which provides an "optical biopsy" or in vivo imaging of various ocular
surface and corneal pathologies, allowing the clinician to diagnose diseases
otherwise not visualized by traditional methods. The utility of anterior segment
OCT for various anterior segment pathologies is reviewed.
PMID- 29942816
TI - Arthroscopic-Assisted Latissimus Dorsi Tendon Transfer for Massive Rotator Cuff
Tears: A Systematic Review.
AB - Background: Arthroscopic-assisted latissimus dorsi tendon transfer (LDTT) has
shown promising results with good outcomes in patients with massive rotator cuff
tears (MRCTs), as reported by individual studies. However, to the best of the
authors' knowledge, no systematic review has been performed to assess the
collective outcomes of these individual studies. Purpose/Hypothesis: The primary
purpose of this study was to assess patient outcomes after arthroscopic-assisted
LDTT for the management of MRCTs. The secondary objectives were to report on the
management of MRCTs, including diagnostic investigations, surgical decision
making, and arthroscopic techniques, as well as to evaluate the quality of
evidence of the existing literature. It was hypothesized that nearly all patients
were satisfied with arthroscopic-assisted LDTT and that they experienced
improvements in pain symptoms, function, and strength after the procedure, with
an overall complication rate of less than 10%. Study Design: Systematic review;
Level of evidence, 4. Methods: The databases MEDLINE, Embase, and PubMed were
searched from database inception (1946) until August 18, 2017, with titles,
abstracts, and full-text articles screened independently by 2 reviewers.
Inclusion criteria were English-language studies investigating arthroscopic
assisted LDTT for the management of MRCTs on patients of all ages. Conference
papers, book chapters, review articles, and technical reports were excluded. The
quality of the included studies was categorized by level of evidence and the
Methodological Index for Non-Randomized Studies (MINORS) checklist. Results: In
total, 8 studies (7 case series [median MINORS score, 7 of 16] and 1 prospective
comparative study [median MINORS score, 14 of 24]) were identified; the studies
included 258 patients (258 shoulders) with MRCTs treated with LDTT using
arthroscopic-assisted techniques. The decision to pursue surgery was based on
both clinical findings and investigations in 5 studies, investigations only in 2
studies, and clinical findings only in 1 study. Overall, 88% of patients were
satisfied with the results of surgery and experienced significant improvement in
their symptoms, including shoulder pain, strength, range of motion, and overall
function, over a mean follow-up period of 34.3 months. Overall, there was a low
rate of complications (7%) associated with the procedure. Conclusion:
Arthroscopic-assisted LDTT for MRCTs provides patients with marked improvement in
shoulder pain, strength, and function, and the procedure is associated with a low
risk of complication. Further high-quality comparative studies are warranted to
validate these findings in comparison with other operative techniques.
PMID- 29942818
TI - On the Role of Different Age Groups and Pertussis Vaccines During the 2012
Outbreak in Wisconsin.
AB - Background: There is limited information on the roles of different age groups in
propagating pertussis outbreaks, and on the impact of vaccination on pertussis
transmission in the community. Methods: The relative roles of different age
groups in propagating the 2012 pertussis outbreak in Wisconsin were evaluated
using the relative risk (RR) statistic that measures the change in the group's
proportion among all detected cases before vs after the epidemic peak. The impact
of vaccination in different age groups against infection (that is potentially
different from the protective effect against detectable disease) was evaluated
using the odds ratios (ORs), within each age group, for being vaccinated vs
undervaccinated before vs after the outbreak's peak. Results: The RR statistic
suggests that children aged 13-14 years played the largest relative role during
the outbreak's ascent (with estimates consistent across the 3 regions in
Wisconsin that were studied), followed by children aged 7-8, 9-10, and 11-12
years. Young children and older teenagers and adults played more limited relative
roles during the outbreak. Results of the vaccination status analysis for the
fifth dose of DTaP (for children aged 7-8 years: OR, 0.44; 95% confidence
interval [CI], 0.23-0.86; for children aged 9-10 years: OR, 0.51; 95% CI, 0.27
0.95); and for Tdap for children aged 13-14 years (OR, 0.38, 95% CI, 0.16-0.89)
are consistent with protective effect against infection. Conclusions: While our
epidemiological findings for the fifth dose of DTaP and for Tdap are consistent
with protective effect against infection, further studies, including those
estimating vaccine effectiveness against infection/transmission to others
particularly for pertussis vaccines for adolescents, are needed to evaluate the
impact of vaccination on the spread of pertussis in the community.
PMID- 29942820
TI - Gastrointestinal Events in High-Dose vs Standard-Dose Influenza Vaccine
Recipients.
AB - Passive surveillance data had signaled the possibility of gastrointestinal
adverse events occurring after the administration of high-dose inactivated
influenza vaccine (IIV-HD). However, in a large, prospective randomized clinical
trial, rates of serious gastrointestinal events were no greater among IIV-HD
recipients than among those who received a standard-dose influenza vaccine.
PMID- 29942819
TI - Cerebral Oximetry for Detecting High-mortality Risk Patients with Cryptococcal
Meningitis.
AB - Background: Cryptococcus is the commonest cause of adult meningitis in Africa,
with 50%-70% experiencing increased intracranial pressure. Cerebral oximetry is a
noninvasive near-infrared spectroscopy technology to monitor percent regional
cerebral tissue oxygenation (rSO2). We assessed if cerebral oximetry predicts
meningitis mortality. Methods: We performed cerebral oximetry within 14 days of
cryptococcal meningitis diagnosis on 121 Ugandans from April 2016 to September
2017. We evaluated baseline rSO2 association with mortality by multivariable
logistic regression and correlation with other clinical factors. We compared
groups formed by initial rSO2 <30% vs >=30% for longitudinal change with mixed
effects models. We measured change in %rSO2 before and after lumbar puncture
(LP). Results: The median initial rSO2 (interquartile range) was 36% (29%-42%),
and it was <30% in 29% (35/121). For 30-day mortality, the unadjusted odds ratio
(per 5% increase in rSO2) was 0.73 (95% confidence interval [CI], 0.58 to 0.91; P
= .005). Those with initial rSO2 <30% had 3.4 (95% CI, 1.5 to 8.0) higher odds of
30-day mortality than those with initial rSO2 >=30%. Hemoglobin correlated with
initial rSO2 (rho = .54; P < .001), but rSO2 did not correlate with pulse
oximetry, intracranial pressure, cerebral perfusion pressure, or quantitative
cerebrospinal fluid culture, and rSO2 was unchanged pre/post-lumbar punctures.
The longitudinal rSO2 measurements change was 15% (95% CI, 12% to 18%) lower in
the group with initial rSO2 <30%. Conclusions: Individuals with cryptococcal
meningitis and low cerebral oximetry (rSO2 < 30%) have high mortality. Cerebral
oximetry may be useful as a prognostic marker of mortality. Targeted
interventions to improve rSO2 should be tested in trials to try to decrease
mortality in meningitis.
PMID- 29942822
TI - Inflammation Associates With Impaired Small Arterial Elasticity Early in HIV
Disease.
AB - We estimated small arterial elasticity and used linear regression to evaluate its
association with inflammatory biomarkers among antiretroviral therapy-naive, HIV
positive patients with high CD4+ counts. After adjustment, high-sensitivity C
reactive protein and interleukin-6 were inversely associated with small arterial
elasticity. These data suggest that systemic inflammation may contribute to
vascular dysfunction even in very early HIV disease.
PMID- 29942821
TI - Towards a Definition for Health Care-Associated Infection.
AB - Background: Health care-associated infection (HcAI) is a term frequently used to
describe community-onset infections likely to be caused by multidrug-resistant
organisms (MDROs). The most frequently used definition was developed at Duke
University Medical Center in 2002 (Duke-2002). Although some professional
societies have based management recommendations on Duke-2002 (or modifications
thereof), neither Duke-2002 nor other variations have had their performance
measured. Methods: A case-control study was conducted at Assaf Harofeh Medical
Center (AHMC) of consecutive adult bloodstream infections (BSIs). A multivariable
model was used to develop a prediction score for HcAI, measured by the presence
of MDRO infection on admission. The performances of this new score and previously
developed definitions at predicting MDRO infection on admission were measured.
Results: Of the 504 BSI patients enrolled, 315 had a BSI on admission and 189 had
a nosocomial BSI. Patients with MDRO-BSI on admission (n = 100) resembled
patients with nosocomial infections (n = 189) in terms of epidemiological
characteristics, illness acuity, and outcomes more than patients with non-MDRO
BSI on admission (n = 215). The performances of both the newly developed score
and the Duke-2002 definition to predict MDRO infection on admission were
suboptimal (area under the receiver operating characteric curve, 0.76 and 0.68,
respectively). Conclusions: Although the term HcAI is frequently used, its
definition does not perform well at predicting MDRO infection present on
admission to the hospital. A validated score that calculates the risk of MDRO
infection on admission is still needed to guide daily practice and improve
patient outcomes.
PMID- 29942823
TI - Room for Improvement: The HIV-Diabetes Care Continuum Over 15 Years in the
Women's Interagency HIV Study.
AB - Background: Gains in life expectancy through optimal control of HIV infection
with antiretroviral therapy (ART) may be threatened if other comorbidities, such
as diabetes, are not optimally managed. Methods: We analyzed cross-sectional data
of the Women's Interagency HIV Study (WIHS) from 2001, 2006, and 2015. We
estimated the proportions of HIV-positive and HIV-negative women with diabetes
who were engaged in care and achieved treatment goals (hemoglobin A1c [A1c]
<7.0%, blood pressure [BP] <140/90 mmHg, low-density lipoprotein [LDL]
cholesterol <100 mg/dL, not smoking) and viral suppression. Repeated-measures
models were used to estimate the adjusted prevalence of achieving each diabetes
treatment goal at each time point, by HIV status. Results: We included 486 HIV
positive and 258 HIV-negative women with diabetes. In 2001, 91.8% visited a
health care provider, 60.7% achieved the A1c target, 70.5% achieved the BP
target, 38.5% achieved the LDL cholesterol target, 49.2% were nonsmokers, 23.3%
achieved combined ABC targets (A1c, BP, and cholesterol), and 10.9% met combined
ABC targets and did not smoke. There were no differences by HIV status, and
patterns were similar in 2006 and 2015. Among HIV-positive women, viral
suppression increased from 41% in 2001 to 87% in 2015 compared with 8% and 13%
achieving the ABC goals and not smoking. Viral suppression was not associated
with achievement of diabetes care goals. Conclusions: Successful management of
HIV is outpacing that of diabetes. Future studies are needed to identify factors
associated with gaps in the HIV-diabetes care continuum and design interventions
to better integrate effective diabetes management into HIV care.
PMID- 29942824
TI - Rheumatic Heart Disease Prophylaxis in Older Patients: A Register-Based Audit of
Adherence to Guidelines.
AB - Background: Prevention of rheumatic heart disease (RHD) remains challenging in
high-burden settings globally. After acute rheumatic fever (ARF), secondary
antibiotic prophylaxis is required to prevent RHD. International guidelines on
recommended durations of secondary prophylaxis differ, with scope for clinician
discretion. Because ARF risk decreases with age, ongoing prophylaxis is generally
considered unnecessary beyond approximately the third decade. Concordance with
guidelines on timely cessation of prophylaxis is unknown. Methods: We undertook a
register-based audit to determine the appropriateness of antibiotic prophylaxis
among clients aged >=35 years in Australia's Northern Territory. Data on
demographics, ARF episode(s), RHD severity, prophylaxis type, and relevant
clinical notes were extracted. The determination of guideline concordance was
based on whether (1) national guidelines were followed; (2) a reason for
departure from guidelines was documented; (3) lifelong continuation was
considered appropriate in all cases of severe RHD. Results: We identified 343
clients aged >=35 years prescribed secondary prophylaxis. Guideline concordance
was 39% according to national guidelines, 68% when documented reasons for
departures from guidelines were included and 82% if patients with severe RHD were
deemed to need lifelong prophylaxis. Shorter times since last echocardiogram or
cardiologist review were associated with greater likelihood of guideline
concordance (P < .001). The median time since last ARF was 5.9 years in the
guideline-concordant group and 24.0 years in the nonconcordant group (P < .001).
Thirty-two people had an ARF episode after age 40 years. Conclusions: In this
setting, appropriate discontinuation of RHD prophylaxis could be improved through
timely specialist review to reduce unnecessary burden on clients and health
systems.
PMID- 29942825
TI - Risk Factors for Self-Reported Cholera Within HIV-Affected Households in Rural
Haiti.
AB - Background: Cholera continues to be a major cause of morbidity and mortality
worldwide and is now endemic in Haiti since first being introduced in 2010.
Cholera and HIV have significant geographic overlap globally, but little is known
about the clinical features and risk of cholera among HIV-infected people and
their households. Methods: We assessed HIV-affected households originally
recruited for a randomized controlled trial of food supplements. We assessed for
correlation between household and individual factors and reported history of
cholera since 2010 using univariable and multivariable analyses. Results: There
were 352 HIV-infected household members, 32 with reported history of medically
attended cholera, and 1968 other household members, 55 with reported history of
medically attended cholera. Among HIV-infected individuals in this study, no
variables correlated with reported history of cholera in univariable analyses.
Among all household members, known HIV infection (adjusted odds ratio [AOR],
3.75; 95% CI, 2.43-5.79; P < .0001), source of income in the household (AOR,
1.82; 95% CI, 1.05-3.15; P = .034), time required to fetch water (AOR, 1.07 per 5
minute increase; 95% CI, 1.01-1.12; P = .015), and severe household food
insecurity (AOR, 3.23; 95% CI, 1.25-8.34; P = .016) were correlated with reported
history of cholera in a multivariable analysis. Conclusions: Known HIV infection,
source of household income, time required to fetch water, and severe household
food insecurity were independently associated with reported history of medically
attended cholera in HIV-affected households in rural Haiti. Further research is
required to better understand the interactions between HIV and cholera.
PMID- 29942827
TI - A brief overview of the 2016 Neurobiology of Stress Workshop.
PMID- 29942826
TI - Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for
Mucopolysaccharidoses.
AB - Mucopolysaccharidoses (MPSs) are inherited metabolic diseases caused by the
deficiency of lysosomal enzymes needed to catabolize glycosaminoglycans (GAGs).
Four therapeutic options are currently considered: enzyme replacement therapy,
substrate reduction therapy, gene therapy, and hematopoietic stem cell
transplantation. However, while some of them exhibit limited clinical efficacy
and require high costs, others are still in development. Therefore, alternative
treatments for MPSs need to be explored. Here we describe an innovative
therapeutic approach based on the use of a recombinant protein that is able to
bind the excess of extracellular accumulated heparan sulfate (HS). We demonstrate
that this protein is able to reduce lysosomal defects in primary fibroblasts from
MPS I and MPS IIIB patients. We also show that, by masking the excess of
extracellular accumulated HS in MPS fibroblasts, fibroblast growth factor (FGF)
signal transduction can be positively modulated. We, therefore, suggest the use
of a competitive binding molecule for HS in MPSs as an alternative strategy to
prevent the detrimental extracellular substrate storage.
PMID- 29942828
TI - Data on horizontally transferred genes in California two-spot octopus, Octopus
bimaculoides.
AB - Horizontal gene transfer (HGT), a mechanism that shares genetic material between
the host and donor from separated offspring branches, has been described as a
means of producing novel and beneficial phenotypes for the host organisms. In the
present study, 12 HGT genes were identified from California two-spot octopus
Octopus bimaculoides based on a similarity search, phylogenetic construction,
gene composition analysis and PCR (Polymerase Chain Reaction) validation. The
data collected from the HGT genes from octopus, indicating the phylogenetic
incongruences, CodonW analysis, PCR products, detailed motifs and organisms used
in screening. In phylogenetic screening, those genes were nested within bacteria
homologs and identified as HGT genes transferred from the bacteria to the
octopus. The motifs were similar in proteins of the horizontally acquired Zn
metalloproteinases, but differed to endogenous proteins. CodonW was employed to
investigate the codon usage bias between HGT genes and other genes in the octopus
genome. In PCR validation, all the HGT genes could be produced as amplified
fragments. The results collectively indicated the existence of HGT in molluscs
and its potential l contribution to the evolution of octopus with regards to
functional innovation and adaptability.
PMID- 29942829
TI - Reverse Koebner phenomenon induced by the Mantoux test in erythrodermic
psoriasis: A case report and literature review.
PMID- 29942830
TI - The importance of lymph node examination: Simultaneous diagnosis of hypopigmented
mycosis fungoides and follicular B-cell lymphoma.
PMID- 29942831
TI - Case report-delayed splenic rupture in combination with medial femoral neck
fracture after low energy trauma. Development of hemorrhagic shock 5 days after
hip prosthesis due to a rare cause.
AB - A 79 year old female patient was admitted to our emergency department with a
fracture of the right medial femoral neck six days after a fall on her right side
and a cemented hemiprosthesis was implanted. Five days later, she developed a
hemorrhagic shock and was diagnosed with a delayed splenic rupture and the spleen
was resected. Histopathological examination showed a delayed rupture of an
otherwise normal spleen without signs of an underlying pathology. The outcome was
fatal: In the postoperative course she developed pneumonia, three weeks later she
succumbed due to multiple organ failure. Even careful reevaluation of the case
did not provide any clues to expect an injury of the spleen according to trauma
mechanism. This case shows that delayed splenic rupture of a normal spleen may
occur even after a low energy trauma. Injury of the spleen should therefore
always be considered, even with an uncharacteristic anamnesis. Physical
examination after trauma should therefore always include a careful clinical
evaluation. The clinical threshold for a FAST examination should be low. The
coincidence of a femoral neck fracture and a splenic rupture after a low energy
trauma has not been reported before.
PMID- 29942832
TI - Severe ocular trauma-The hidden danger of plastic bottles when throwing out the
rubbish.
AB - This is the first reported case of ocular trauma caused by a plastic bottle cap
occurring accidentally without misuse. The mechanism involved an un-emptied
plastic bottle containing orange juice being thrown away with other rubbish. The
combination of this minor impact and the pressure built up within the bottle
through fermentation caused expulsion of the cap at high velocity. This cap
caused severe ocular trauma requiring urgent ophthalmic assessment and
intervention. Our simple recommendation is that plastic bottles have their caps
removed and are emptied before being thrown away.
PMID- 29942833
TI - Recovery after fracture dislocation of L3/L4 ASIA B: Case report.
AB - In fracture dislocations of the lumbar region, two anatomical facts can help
preserve neurological damage in patients, when compared with trauma in the
cervical or thoracic region. Firstly, the spinal cord in adults extends only to
the lower edge of the first lumbar vertebra, and secondly, the large vertebral
space in this region gives ample space for the roots of the cauda equine. As a
result, the nerve injury may be minimal, because the nerve roots in this region
are accommodated in a larger area, with less content and space. This study
presents the case of a 48-year-old male, a construction worker, who suffered a
fall from a height of approximately 15 meters, directly hitting the lumbar region
against a beam, and presenting pain and inability to move the legs. The patient
was brought to the emergency room 1 hour after the accident, clinically assessed,
submitted to x-rays and a CT scan, and diagnosed as having an ASIA B L3-L4
fracture dislocation. Three hours after the accident, reduction was performed via
posterior transpedicular fixation. One week later, an anterior approach was
performed. The patient progressed to ASIA C 24 hours after the first surgery.
Three months later, the patient was functional with ASIA D and good sphincter
control. The author's purpose is to show the results obtained by an intervention
in the initial hours of the trauma, which helped promote the evolution from a
nonfunctional injury to a functional one, with near-total recovery.
PMID- 29942834
TI - Chronic leg swelling and palpitation as a late complication of post-traumatic
arteriovenous fistula: A case report.
AB - Introduction: Chronic post-traumatic arteriovenous fistula (AVF) is a late
complication of vascular injury and can be presented with symptoms of congestive
heart failure, venous hypertension and distal ischaemia. We present an unusual
case of chronic leg swelling in adult caused by post-traumatic AVF. Case
presentation: A 52 year old white-male patient complained of palpitation, pain
and swollen right leg. Arterial pulses distally from the groin were present. His
medical history revealed him to have sustained gunshot injury of the left thigh 5
years before. Angiography showed a large AVF between superficial femoral artery
and femoral vein. The patient underwent surgical repair of AVF with ligation of
AVF between superficial femoral artery under spinal anaesthesia. Completion
angiography confirmed AVF exclusion. Leg swelling healed within a month.
Conclusion: Post-traumatic fistula should be obliterated as soon as possible.
Untreated fistula results in complications including renin-mediated hypertension
and high-output heart failure, venous and/or arterial insufficiency.
PMID- 29942835
TI - The first description in the literature, of a complication during the extraction
of a retrograde expandable intra-medullary nail in three patients.
AB - Ankle fractures in elderly people are low-energy fractures characterised by
fragility. In the majority, they are unstable and challenging to manage.
Retrograde expandable intra-medullary nails (Fixion(r), Biomet Merck Limited)
inserted through the calcaneum across the sub-talar and ankle joints into the
tibia have been successfully used in the treatment of fragility fractures and non
unions of the distal tibia and ankle, where the use of an antegrade locked nail
would not provide adequate fracture stability for union. Primary fracture
management involves removing the nail at least 3-4 months after radiological
check. In cases of treatment of non-unions a longer treatment period is often
required before removal of nail is considered. We present three patients where
breakage of the Fixion(r) nail during surgery caused problems in nail extraction.
PMID- 29942836
TI - Fracture of the acetabulum with femoral artery injury presenting late: A case
report.
AB - This study reports a rare case of both column acetabulum fracture with femoral
artery injury that presented late and was managed with arterial reconstruction
and fracture fixation. A thirty-one year old man sustained both column acetabular
fracture on the left in a motor vehicle accident. On admission there was no
obvious neuro-vascular deficit. During surgery for the fracture after 7 days of
the injury the femoral artery was found to be severely crushed with no blood
flow. The anterior column of the acetabulum was stabilised followed by resection
and reconstruction of the femoral artery. The post-operative period was
uneventful and he was discharged normally. At 6 months from injury the fractures
had united well with excellent limb circulation and good lower limb function.
Femoral artery injury with acetabular fracture is rare and late presentations are
unreported hitherto. The results of fracture stabilisation and vessel
reconstruction seem to be excellent. Literature of similar injuries is reviewed.
PMID- 29942837
TI - Case report: AVN of the femoral head five year follow-up of the combination of
ipsilateral femoral neck and sub-trochanteric fracture.
AB - To our knowledge, the type of combination of ipsilateral femoral neck and sub
trochanteric fracture is rare. And the long term follow-up is seldom been
reported. A 60 year old woman suffered from a traffic accident. We gave her the
intramedullary nail treatment for the combination of ipsilateral femoral neck and
sub-trochanteric fracture, and the fracture indeed cured after one year and there
is no clue of necrosis of the femoral head, but after 5 years, there is an
evidence of necrosis of the femoral head. Combination of ipsilateral femoral neck
and sub-trochanteric fracture should be kept in mind. Patients with this unusual
fracture should be kept under surveillance for longer than might be thought
currently to be necessary for there is a possibility of necrosis of the femoral
head, even a nondisplaced femoral neck fracture.
PMID- 29942839
TI - Lateral plating of the temporal bone: Hemostatic technique for complex transverse
fractures of the petrous temporal bone.
AB - Background: Transverse petrous temporal bone fractures are commonly associated
with significant intracranial trauma. Diastases of these fractures can lead to
issues with hemostasis in the setting of venous sinus or petrous internal carotid
artery (ICA) injuries. Objective: To describe a rare case of a severe displaced
transverse petrous temporal bone fracture with impending intra-operative
exsanguination, treated with fracture reduction and lateral plating in order to
achieve hemostasis. Methods: We retrospectively reviewed the records of a patient
admitted to the neurosurgical department with a hyperacute epidural hematoma
(EDH) secondary to a transverse petrous temporal bone fracture with venous sinus
and petrous ICA injuries. Results: A 22 year old male was admitted for a severe
traumatic brain injury leading to a left displaced transverse petrous temporal
bone fracture and a hyperacute EDH. Given the location of the fractures, injury
to the venous sinus (at the area of the transverse-sigmoid junction) and petrous
ICA was suspected.Intra-operatively, significant blood loss from both the venous
sinus and petrous ICA was encountered. Given the displaced temporal bone
fracture, packing of the areas was impaired.We performed a manual reduction of
the temporal fracture, followed by lateral plating in order to achieve hemostasis
from the petrous ICA and aid with packing of the venous sinus injury.
Conclusions: Reduction and lateral plating of displaced transverse petrous
temporal bone fractures can aid significantly with intra-operative hemostasis in
the extreme case of venous sinus and/or petrous ICA injuries.
PMID- 29942838
TI - Comminuted distal humeral fracture treated using the Ilizarov technique in a
patient with rheumatoid arthritis and osteoporosis.
AB - The goal of treatment for distal humeral fractures in patients with rheumatoid
arthritis (RA) is to obtain sufficient bone union and good elbow function.
However, treating comminuted distal humeral fractures in patients with RA and
osteoporosis is challenging. We present the case of a 58-year-old woman with RA
and osteoporosis who suffered a comminuted distal humeral fracture and was
successfully treated with the Ilizarov technique. The Ilizarov technique is
minimally invasive compared with conventional open surgery, can obtain good
stabilization, and allows earlier rehabilitation, even if the fractured bone is
severely osteoporotic. The patient exhibited good elbow function and alignment at
the final follow-up examination (18 postoperative months). To the best of our
knowledge, the present case is the first in which a comminuted distal humeral
fracture in a patient with RA and severe osteoporosis was successfully treated
with an Ilizarov external fixator.
PMID- 29942840
TI - Osteochondral autograft transfer for post-traumatic osteochondral defects of the
anterolateral surface of the distal tibial plafond.
AB - Post-traumatic osteochondral defects of the distal tibial plafond may be a more
common cause of pain and osteoarthritis than previously recognized. However, the
literature on the surgical treatment of osteochondral defects of the distal
tibial plafond is significantly limited. This case report presents the operative
technique and clinical outcome of osteochondral autograft transfer for an
osteochondral defect on the anterolateral surface of the distal tibial plafond. A
case of transfer of osteochondral autograft plugs to repair the anterolateral
surface of the distal tibial plafond and prevent progression of forward
displacement of the talus in a 25-year-old man who presented with pain in his
right ankle, following a history of trauma.
PMID- 29942841
TI - Simultaneous bilateral femoral neck fracture in a patient with renal
osteodystrophy.
AB - We present a unique case of displaced simultaneous bilateral fractures, Garden 3
type, in a 49 year woman treated with non-cemented total hip arthroplasty. The
patient showed a Harris hip score of 86 on the right hip and a 81 on the left
side on the fourth postoperative year, besides a bilateral Trendelenburg gait,
more pronounced on the right side. She needed a cane to walk, and felt pain in
the left thigh. The X-ray showed a shortening of 0.9 cm and a left femoral varus.
The other arthroplasty components showed good osseointegration and position. We
found that the use of the uncemented total hip arthroplasty to treat a
simultaneous bilateral fracture in renal osteodystrophy patients has satisfactory
results at a four year follow-up. According to the OCEBM Levels of Evidence
Working Group, this study is graded as a Level of Evidence IV.
PMID- 29942842
TI - Irreducible dorsal dislocation of the interphalangeal joint of the big toe: a
case report.
AB - Irreducible dislocation of the interphalangeal joint (IPJ) big toe is a rare
injury Hitori et al. (2006) . We report a case of the right big toe IPJ
dislocation following a trauma. The problem was diagnosed and managed at other
medical centers with standard treatment of closed manual reduction and splint.
The right big toe was splinted accordingly and the patient was referred to our
orthopedic outpatient clinic. At the clinic, a repeat plain radiograph was
ordered due to high suspicion of the irreducible IPJ.
PMID- 29942843
TI - Delayed chest wall hematoma caused by progressive displacement of rib fractures
after blunt trauma.
AB - Rib fracture is a common injury resulting from blunt thoracic trauma. Although
hemothorax and pneumothorax are known delayed complications of rib fracture,
delayed chest wall hematoma has rarely been reported. We discuss the case of an
81-year-old woman who was not undergoing antiplatelet or anticoagulant therapy
who presented to our emergency department after a traffic injury. This patient
had a nondisplaced rib fracture that went undetected on the initial computed
tomography scan; the development of progressive displacement led to hemorrhagic
shock due to delayed chest wall hematoma. The chest wall hematoma was effectively
diagnosed and treated via contrast-enhanced computed tomography and angiographic
embolization. This case highlights the possibility of this potential delayed
complication from a common injury such as a rib fracture.
PMID- 29942844
TI - A novel technique for reimplanting extruded bone fragments in open fractures.
AB - Extruded bone fragments are a rare complication of high-energy open fractures.
Generally, management is thorough debridement and managing the bone defect. In
the literature, there are only a few case reports where successful retention of
the free bone fragment has been done. Disinfection of bone fragment is done by
autoclaving or use of antiseptic/antibiotic solution. Autoclaving leads to
complete loss of viable cells and antiseptic/antibiotic solutions do not
disinfect completely. In this case report, authors present an innovative
technique of disinfecting the bone fragment effectively with minimum compromise
on biology. A 38-year-old male with compound grade III B comminuted fracture of
distal femur with 2 extruding bone pieces was managed by thorough debridement,
external fixator and antibiotic cement spacer. The extruded bone fragments were
rinsed in saline and diluted betadine and implanted in subfascial plane in
healthy soft tissues in the thigh along with a few antibiotic beads for assuring
disinfection. After 1 week, when no clinical signs of infection were found, the
site was opened, cement spacer removed, free fragments positioned anatomically
and rigid internal fixation was done. Fracture united at 6 months with good
functional outcome. At last follow-up at 1 year, the patient was mobilising
freely and there were no signs of low grade infection. The key points of this
procedure are:1)Viability of bone fragment maintained while achieving
disinfection.2)Traumatised soft tissues healed and prepared for accepting the
free bone fragment.3)Use of antibiotic cement counters any remaining chances of
infection after thorough debridement.4)Faster union with maintenance of bone
length and alignment with use of anatomic fragments. Extensive search of
literature was done and this procedure was found to be novel. A larger case
series can help in determining the utility of this technique in compound
fractures.
PMID- 29942845
TI - Blunt pharyngeal trauma detected by ultrasound sonography: A case report.
AB - Pharyngeal perforation related to blunt neck trauma is a rare clinical entity.
Here in, we report a case of pharyngeal perforation secondary to minor blunt neck
trauma. A 46 year old female was brought to our emergency room with neck pain.
She fell down and hit her neck directly to the edge of a bed. There was no
crepitation in physical examination. Neck ultrasound showed a small amount of air
in her deep neck space. Followed CT and nasopharyngeal scope supported the
presence of pharyngeal perforation. So emergency exploration was done. We found a
laceration of hypopharynx and it was repaired. She could discharged without any
complication on day 7. The indirect finding of pharyngeal perforation is
subcutaneous emphysema. However if the air is localized only in deep cervical
space, physical assessment is difficult. Although CT scan is potent modality to
find air in the deep organs, ultrasound may be alternatives. Emphasis is based on
the suspicion that minor blunt neck trauma may cause pharyngeal perforation.
PMID- 29942846
TI - Extra nuchal-type fibroma associated with repetitive blunt trauma during
religious activities.
AB - Nuchal-type fibroma (NTF) is a rare, benign subcutaneous tumor that usually
arises from the posterior neck. NTF is histologically characterised by dense
collagen bundles and sparse fibroblasts. Only four trauma-related cases have been
previously published. Herein, we present a case of extra NTF with histopathology,
and six palanquin porters by using snowball sampling technique in ethnographic
field research. A palanquin is a type of human-powered transport carried upon the
shoulders mostly seen in religious processions. All individuals (mean age, 26.8
years) displayed similar shoulder masses measuring up to 12 cm in the greatest
dimensions. They averaged approximately 8.1 years of palanquin-carrying work
each. We believe that long-term, heavy shoulder weight bearing of palanquins in
religious dance performances may attribute to the incidence of extra NTF. This
study reviews all literature of trauma-associated NTF through PubMed database,
and highlights the association between repetitive blunt trauma and the
development of NTF.
PMID- 29942847
TI - Hypothermia and near-drowning associated with life-threatening injuries: A
remarkable recovery: A case report.
AB - A young male suffered multiple severe injuries after a fall and near-drowning. On
presentation to the emergency department (ED), he was in a critical and unstable
condition and his chances of survival were deemed very low. This case illustrates
the management of the hypothermic multi-trauma patient and the remarkable
recovery made possible by a high standard of care.
PMID- 29942848
TI - Post-traumatic pancreatico-dural fistula: Case report and management challenges.
AB - Pancreatic injury can occur following high-energy blunt trauma to the torso.
Although several types of pancreatic fistulas have been described in literature,
we report to our knowledge, the first case of a pancreatico-dural fistula of
traumatic origin. A 20-year-old male sustained a severe blow to the thoraco
abdominal region in the setting of a motorcycle accident. A total body scan
revealed an AAST (American Association for the Surgery of Trauma) grade 4 splenic
injury. A laparotomy with splenectomy and abdominal packing was performed. This
was later followed by thoracolumbar instrumentation for posterior fixation of a
T11-T12 transdiscal type C fracture with anterior subluxation of T11, according
to the AO classification. Subsequent management was complicated by the
persistence of a pseudomeningocele despite multiple surgical drainage procedures
and a concomitant increase in retroperitoneal fluid collections. High levels of
amylase and lipase in the pseudomeningocele fluid confirmed the presence of a
pancreatico-dural fistula, due to a Wirsung duct rupture. This case report
illiustrates the challenges in the management of this rare condition.
PMID- 29942849
TI - More than just a urinary catheter - Haemorrhage control by using a Foley catheter
in a penetrating aortic root injury.
AB - The prevalence of great vessel injuries in thoracic trauma is reported at 0.3
10%, predominantly due to a penetrating mechanism. Thoracic aortic injuries, more
specifically those within proximity of the aortic root are challenging to manage
and unceasing bleeding hampers adequate visualisation for performing repair. We
report a case of a 31-year-old male that presented to the emergency department 1
h after sustaining a stab wound injury within proximity of the left upper sternal
border. Vital signs were stable on presentation. Physical examination revealed a
1.5 cm laceration in the 3rd intercostal space. Chest X-ray revealed a small left
pneumothorax, FAST scan was negative, and CT of the chest revealed left sided
haemopneumothorax and haemopericardium. The patient was emergently transferred to
the operating room where median thoracotomy was performed. A significant amount
of bleeding was observed originating from a 1 cm laceration of the aortic root.
Bleeding was controlled using a Foley catheter after unsuccessful attempts of
digital compression, and the laceration was repaired using pledgeted sutures.
Postoperative echocardiography and CT scan of the chest revealed normal cardiac
functions with resolution of haemopericardium and haemopneumothorax, and the
patient was discharged in a stable condition. High index of suspicion should be
maintained for injury to the great vessels in patients with penetrating chest
injuries, despite apparent haemodynamic stability. In this case, balloon
tamponade using a Foley catheter served as a quick and simple technique that
resulted in an almost bloodless field, facilitating adequate visualisation for
definitive repair. Although the use of this technique has been previously
described, this report serves as a reminder that a Foley catheter can be
successfully used for balloon catheter tamponade in injuries to the aortic root.
PMID- 29942850
TI - Management of severe traumatic flexion-distraction injuries in a multisystem
trauma patient: A case report.
AB - Study design: Case report and relevant literature review. Objective: To discuss
the management of severe flexion-distraction injury of the subaxial cervical
spine in a multisystem trauma patient. Summary of background data: Traumatic
cervical spine injury from flexion-distraction injury can cause significant
instability requiring extensive instrumentation complicated by vascular and soft
tissue injuries. Methods: The medical record of a patient who suffered traumatic
flexion-distraction injury was reviewed for relevant clinical and radiology data.
A literature review on the management of traumatic cervical injuries was
performed using the PubMed database. Results: We report a case of 21-year-old
woman who suffered a C5-C6 flexion-distraction injury. After she underwent
anterior cervical discectomy and fusion (ACDF), her care was transferred to the
senior author (S.K.) due to the severity of the distraction. The patient returned
to the OR the next day and underwent removal of implants at C5 and corpectomy
with anterior and posterior instrumentation. Conclusion: There are many ways to
manage a flexion-distraction injury of the cervical spine. In a polytrauma
patient, the surgical strategy can become complex. We present a surgical option
with an acceptable outcome.
PMID- 29942851
TI - Perineal impalement injury by steel bar - A near miss.
AB - Adult perianal impalement injuries are uncommon but can carry high morbidity and
mortality. We report a case of a penetrating perineal trauma in a construction
worker highlighting an innovative use of a Sengstaken tube to control his pelvic
bleeding, as well as the operative management of his sphincteric injury. This
article illustrates principles of effective acute care and discusses a diagnostic
approach to evaluating a potentially complex injury, as well as the decision
making process with regard to fecal diversion and choice of sphincteric repair.
PMID- 29942852
TI - Multi-trauma secondary to hypocalcaemia-induced seizure: A case report.
AB - Introduction: Fractures are known sequelae of seizures. We present a young male
with bilateral acetabula and surgical neck of humerus (SNOH), right neck of femur
(NOF) and thoracolumbar fractures in the context of a hypocalcaemic seizure
secondary to severe malnutrition, secondary hyperparathyroidism and vitamin D
deficiency. The authors believe that numerous severe injuries in a single patient
secondary to seizure are extremely rare and have not been seen in the literature.
Case report: A 25-year-old male presented to A&E following a collapse. He
described limited movement and pain in all four limbs and collateral history
described a generalised tonic-clonic seizure. XR and CT identified pelvic,
femoral and humeral fractures, as well as compression fractures of T11, T12 and
L1 vertebrae. His pelvic, femoral and SNOH fractures all required ORIF with intra
operative biopsy revealing abnormal bone quality. His spinal fractures did not
require management.His young age and severe injuries prompted endocrinology and
neurological evaluation. These revealed severe malnutrition secondary to
behavioural and dietary factors with severe hypocalcaemia, secondary
hyperparathyroidism and vitamin D deficiency. His metabolic and nutritional
deficits were replaced intravenously and orally and his seizure attributed to
hypocalcaemia. Discussion and conclusion: Clinical suspicion for fractures should
be high as the rate of fracture following seizure is approximately 6% [1]. Close
evaluation and tertiary survey should be completed as missed musculoskeletal
injury has been reported to be over 10% [2] and pre-existing medical and social
risk factors may increase the incidence of these injuries [3-4].Given the young
man's presentation, a high clinical suspicion was held for an underlying syndrome
such as osteomalacia. Secondary to early aggressive treatment, a biopsy performed
was non-diagnostic and features of osteomalacia were not present. Due to the
potential consequences of a seizure, the authors recommend individuals who
present with seizure or collapse be thoroughly examined and investigated to
ensure no co-existing injury or pathology.
PMID- 29942853
TI - Traumatic isolated perforation of lower oesophagus.
AB - One of the rarest cases of non-iatrogenic oesophageal perforation is falling from
height. We report a case of a 26 year old man with oesophageal perforation
resulting from a fall of 12 meter height. A pneumomediastinum in the absence of a
pneumothorax and contrast extravasation from the oesophagus on CT evoked a
perforation of the aerodigestive tract. No other injuries were seen. A non
operative management was pursued with good outcomes.
PMID- 29942854
TI - Ventricular tachycardia-inducibility predicts arrhythmic events in post
myocardial infarction patients with low ejection fraction. A systematic review
and meta-analysis.
AB - Background: Inducibility of ventricular arrhythmias at electrophysiological study
(EPS) has long been suggested as predictive for subsequent arrhythmic events.
Nevertheless, the usefulness of EPS in the clinical practice is still unclear. We
performed a systematic review and meta-analysis to assess the predictive power of
EPS in primary prevention of ventricular arrhythmias in post-myocardial
infarction (MI) patients with left ventricular dysfunction. Methods: MEDLINE and
the Cochrane Library databases were systematically searched to identify studies,
which analyzed EPS predictive value in post-MI patients with mean EF < 40% for
the composite arrhythmic endpoint defined by: sudden cardiac death (SCD), aborted
SCD, ventricular tachycardia (VT), ventricular fibrillation (VF), appropriate
implantable cardioverter-defibrillator (ICD) interventions. Results: Nine
studies, evaluating 3959 patients with 647 arrhythmic events, were included in
the meta-analyses. EPS showed a strong predictive power for the arrhythmic
endpoint with a pooled odds ratio (OR) of 4.00 (95% confidence interval [CI]:
2.30-6.96) in the whole set of studies, albeit a high level of heterogeneity
among studies. EPS predictive power was higher in studies where VT-inducibility
was tested (OR 6.52; 95% CI: 2.30-18.44; sensitivity 0.65, specificity 0.78, and
negative predictive value 0.94), versus those assessing VT/VF-inducibility (OR
2.09; 95% CI: 1.34-3.26). VT-inducibility was predictive even when assessed
within one month after MI (OR 7.85; 95% CI: 3.67-16.80). Conclusions:
Inducibility of ventricular arrhythmias at EPS is a strong predictor of the
arrhythmic endpoint in post-MI patients with impaired EF, particularly when VT
inducibility is tested. EPS could help selecting the patients who can mostly
benefit from ICD therapy.
PMID- 29942855
TI - Prognostic implications of high-sensitivity cardiac troponin T assay in a real
world population with non-ST-elevation acute coronary syndrome.
AB - Background: High-sensitivity cardiac troponin T (hsTnT) was recently approved for
clinical use by the Food and Drug Administration. The transition from
contemporary to hsTnT assays requires a thorough understanding of the clinical
differences between these assays. Hypothesis: HsTnT may provide a more accurate
prognostic stratification than contemporary cardiac troponin I (cTnI) in patients
with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Methods: HsTnT
and cTnI were measured in 644 patients with CK-MB negative NSTE-ACS who were
enrolled in the prospective multicenter SPAI (Stratificazione Prognostica
dell'Angina Instabile) study. Patients were stratified at the 99th percentile
reference limit for each assay. The primary endpoint was cardiovascular death
(CVD) or non-fatal myocardial infarction (MI); the secondary endpoint was the
occurrence of unstable angina (UA). Follow-up lasted 180 days. Results: Patients
with hsTnT >=99th percentile were at higher risk of CVD/MI (30-day: 5.9% vs 0.8%,
p = 0.001; 180-day: 11.1% vs 4.7%, p = 0.004), also after adjusting for TIMI Risk
Score. No significant difference in CVD/MI at 180-day was found between hsTnT
positive/cTnI-negative and hsTnT-negative/cTnI-negative patients (adjHR 1.61, 95%
CI 0.74-3.49, p = 0.232). Occurrence of UA was not differently distributed
between hsTnT groups dichotomized at the 99th percentile (12.4% vs 12.5% p =
0.54). Conclusions: Our investigation on a real-world NSTE-ACS population showed
good prognostic performance of hsTnT in the risk stratification of the hard
endpoint, but did not demonstrate the improved prognostic ability of hsTnT over
contemporary cTn. Neither troponin assay predicted the recurrence of UA,
suggesting the acute rise of cardiac troponin as a marker of severity, but not
the occurrence of future coronary instability.
PMID- 29942856
TI - Excited state engineering for efficient reverse intersystem crossing.
AB - Reverse intersystem crossing (RISC) from the triplet to singlet excited state is
an attractive route to harvesting electrically generated triplet excitons as
light, leading to highly efficient organic light-emitting diodes (OLEDs). An
ideal electroluminescence efficiency of 100% can be achieved using RISC, but
device lifetime and suppression of efficiency roll-off still need further
improvement. We establish molecular design rules to enhance not only the RISC
rate constant but also operational stability under electrical excitation. We show
that the introduction of a second type of electron-donating unit in an initially
donor-acceptor system induces effective mixing between charge transfer and
locally excited triplet states, resulting in acceleration of the RISC rate while
maintaining high photoluminescence quantum yield. OLEDs using our designed sky
blue emitter achieved a nearly 100% exciton production efficiency and exhibited
not only low efficiency roll-off but also a marked improvement in operational
stability.
PMID- 29942857
TI - Low temperature rates for key steps of interstellar gas-phase water formation.
AB - The gas-phase formation of water molecules in the diffuse interstellar medium
(ISM) proceeds mainly via a series of reactions involving the molecular ions OH+,
H2O+, and H3O+ and molecular hydrogen. These reactions form the backbone for the
chemistry leading to the formation of several complex molecular species in space.
A comprehensive understanding of the mechanisms involved in these reactions in
the ISM necessitates an accurate knowledge of the rate coefficients at the
relevant temperatures (10 to 100 K). We present measurements of the rate
coefficients for two key reactions below 100 K, which, in both cases, are
significantly higher than the values used in astronomical models thus far. The
experimental rate coefficients show excellent agreement with dedicated
theoretical calculations using a novel ring-polymer molecular dynamics approach
that offers a first-principles treatment of low-temperature barrierless gas-phase
reactions, which are prevalent in interstellar chemical networks.
PMID- 29942858
TI - Materials for lithium-ion battery safety.
AB - Lithium-ion batteries (LIBs) are considered to be one of the most important
energy storage technologies. As the energy density of batteries increases,
battery safety becomes even more critical if the energy is released
unintentionally. Accidents related to fires and explosions of LIBs occur
frequently worldwide. Some have caused serious threats to human life and health
and have led to numerous product recalls by manufacturers. These incidents are
reminders that safety is a prerequisite for batteries, and serious issues need to
be resolved before the future application of high-energy battery systems. This
Review aims to summarize the fundamentals of the origins of LIB safety issues and
highlight recent key progress in materials design to improve LIB safety. We
anticipate that this Review will inspire further improvement in battery safety,
especially for emerging LIBs with high-energy density.
PMID- 29942859
TI - Constraint of a ruthenium-carbon triple bond to a five-membered ring.
AB - The incorporation of a metal-carbon triple bond into a ring system is challenging
because of the linear nature of triple bonds. To date, the synthesis of these
complexes has been limited to those containing third-row transition metal
centers, namely, osmium and rhenium. We report the synthesis and full
characterization of the first cyclic metal carbyne complex with a second-row
transition metal center, ruthenapentalyne. It shows a bond angle of 130.2(3)
degrees around the sp-hybridized carbyne carbon, which represents the recorded
smallest angle of second-row transition metal carbyne complexes, as it deviates
nearly 50 degrees from the original angle (180 degrees ). Density functional
theory calculations suggest that the inherent aromatic nature of these
metallacycles with bent Ru=C-C moieties enhances their stability. Reactivity
studies showed striking observations, such as ambiphilic reactivity, a metal
carbon triple bond shift, and a [2 + 2] cycloaddition reaction with alkyne and
cascade cyclization reactions with ambident nucleophiles.
PMID- 29942860
TI - Direct metabolite detection with an n-type accumulation mode organic
electrochemical transistor.
AB - The inherent specificity and electrochemical reversibility of enzymes poise them
as the biorecognition element of choice for a wide range of metabolites. To use
enzymes efficiently in biosensors, the redox centers of the protein should have
good electrical communication with the transducing electrode, which requires
either the use of mediators or tedious biofunctionalization approaches. We report
an all-polymer micrometer-scale transistor platform for the detection of lactate,
a significant metabolite in cellular metabolic pathways associated with critical
health care conditions. The device embodies a new concept in metabolite sensing
where we take advantage of the ion-to-electron transducing qualities of an
electron-transporting (n-type) organic semiconductor and the inherent
amplification properties of an ion-to-electron converting device, the organic
electrochemical transistor. The n-type polymer incorporates hydrophilic side
chains to enhance ion transport/injection, as well as to facilitate enzyme
conjugation. The material is capable of accepting electrons of the enzymatic
reaction and acts as a series of redox centers capable of switching between the
neutral and reduced state. The result is a fast, selective, and sensitive
metabolite sensor. The advantage of this device compared to traditional
amperometric sensors is the amplification of the input signal endowed by the
electrochemical transistor circuit and the design simplicity obviating the need
for a reference electrode. The combination of redox enzymes and electron
transporting polymers will open up an avenue not only for the field of biosensors
but also for the development of enzyme-based electrocatalytic energy
generation/storage devices.
PMID- 29942861
TI - Self-consistent determination of spin Hall angle and spin diffusion length in Pt
and Pd: The role of the interface spin loss.
AB - Spin Hall angle (thetaSH) and spin diffusion length (lambdasd) are the key
parameters in describing the spin-charge conversion, which is an integral part of
spintronics. Despite their importance and much effort devoted to quantifying
them, significant inconsistencies in the reported values for the same given
material exist. We report a self-consistent method to quantify both thetaSH and
lambdasd of nonmagnetic materials by spin pumping with various ferromagnetic (FM)
pumping sources. We characterize the spin-charge conversion for Pt and Pd with
various FM combinations using (i) effective spin-mixing conductance, (ii)
microwave photoresistance, and (iii) inverse spin Hall effect measurements and
find that the pumped spin current suffers an interfacial spin loss (ISL), whose
magnitude varies for different interfaces. By properly treating the ISL effect,
we obtained consistent values of thetaSH and lambdasd for both Pt and Pd
regardless of the ferromagnet used.
PMID- 29942862
TI - Observation of Poiseuille flow of phonons in black phosphorus.
AB - The travel of heat in insulators is commonly pictured as a flow of phonons
scattered along their individual trajectory. In rare circumstances, momentum
conserving collision events dominate, and thermal transport becomes hydrodynamic.
One of these cases, dubbed the Poiseuille flow of phonons, can occur in a
temperature window just below the peak temperature of thermal conductivity. We
report on a study of heat flow in bulk black phosphorus between 0.1 and 80 K. We
find a thermal conductivity showing a faster than cubic temperature dependence
between 5 and 12 K. Consequently, the effective phonon mean free path shows a
nonmonotonic temperature dependence at the onset of the ballistic regime, with a
size-dependent Knudsen minimum. These are hallmarks of Poiseuille flow previously
observed in a handful of solids. Comparing the phonon dispersion in black
phosphorus and silicon, we show that the phase space for normal scattering events
in black phosphorus is much larger. Our results imply that the most important
requirement for the emergence of Poiseuille flow is the facility of momentum
exchange between acoustic phonon branches. Proximity to a structural transition
can be beneficial for the emergence of this behavior in clean systems, even when
they do not exceed silicon in purity.
PMID- 29942863
TI - Wavelength-tunable and shape-reconfigurable photonic capsule resonators
containing cholesteric liquid crystals.
AB - Cholesteric liquid crystals (CLCs) have a photonic bandgap due to the periodic
change of refractive index along their helical axes. The CLCs containing optical
gain have served as band-edge lasing resonators. In particular, CLCs in a
granular format provide omnidirectional lasing, which are promising as a point
light source. However, there is no platform that simultaneously achieves high
stability in air and wavelength tunability. We encapsulate CLCs with double
shells to design a capsule-type laser resonator. The fluidic CLCs are fully
enclosed by an aqueous inner shell that promotes the planar alignment of LC
molecules along the interface. The outer shell made of silicone elastomer
protects the CLC core and the inner shell from the surroundings. Therefore, the
helical axes of the CLCs are radially oriented within the capsules, which provide
a stable omnidirectional lasing in the air. At the same time, the fluidic CLCs
enable the fine-tuning of lasing wavelength with temperature. The capsules retain
their double-shell structure during the dynamic deformation. Therefore, the CLCs
in the core maintain the planar alignment along the deformed interface, and a
lasing direction can be varied from omnidirectional to bi- or multidirectional,
depending on the shape of deformed capsules.
PMID- 29942864
TI - Sagittal plane assessment of spino-pelvic complex in a Central European
population with adolescent idiopathic scoliosis: a case control study.
AB - Background: Scoliosis is a complex three-dimensional deformity. While the frontal
profile is well understood, increasing attention has turned to balance in the
sagittal plane. The present study evaluated changes in sagittal spino-pelvic
parameters in a large Hungarian population with adolescent idiopathic scoliosis.
Methods: EOS 2D/3D images of 458 scoliotic and 69 control cases were analyzed.
After performing 3D reconstructions, the sagittal parameters were assessed as a
whole and by curve type using independent sample t test and linear regression
analysis. Results: Patients with scoliosis had significantly decreased thoracic
kyphosis (p < 0.001) with values T1-T12, 34.1 +/- 17.1o vs. 43.4 +/- 12.7o in
control; T4-T12, 27.1 +/- 18.8o vs. 37.7 +/- 15.1o in control; and T5-T12, 24.9
+/- 15.8o vs. 32.9 +/- 15.0o in control. Changes in thoracic kyphosis correlated
with magnitude of the Cobb angle (p < 0.001). No significant change was found in
lumbar lordosis and the pelvic parameters. After substratification according to
the Lenke classification and individually evaluating subgroups, results were
similar with a significant decrease in only the thoracic kyphosis. A strong
correlation was seen between sacral slope, pelvic incidence, and lumbar lordosis,
and between pelvic version and thoracic kyphosis in control and scoliotic groups,
whereas pelvic incidence was also seen to be correlated with thoracic kyphosis in
scoliosis patients. Conclusion: Adolescent idiopathic scoliosis patients showed a
significant decrease in thoracic kyphosis, and the magnitude of the decrease was
directly related to the Cobb angle. Changes in pelvic incidence were minimal but
were also significantly correlated with thoracic changes. Changes were similar
though not identical to those seen in other Caucasian studies and differed from
those in other ethnicities. Scoliotic curves and their effect on pelvic balance
must still be regarded as individual to each patient, necessitating individual
assessment, although changes perhaps can be predicted by patient ethnicity.
PMID- 29942865
TI - Emergency department use by paediatric patients in Lombardy Region, Italy: a
population study.
AB - Objectives: To estimate the rate of paediatric attendance at emergency
departments (EDs) in the Lombardy Region, Italy, and to determine the factors
contributing to different patterns of use. Methods: By analysing healthcare
administrative databases, ED attendance by 1.6 million youths <18 years old
during 2012 in the Lombardy Region was assessed. The pattern of use was
categorised based on the number of ED visits and level of emergency, defined by
triage code and outcome of the visit. Logistic regression analyses were performed
to identify the characteristics of access for non-urgent reasons and those of
patients with frequent non-urgent access (>=4 accesses for non-urgent reasons
only). A case-control study was carried out to compare healthcare resource use by
children 1-5 years old who were 'frequent non-urgent users' with that of randomly
selected controls, matched by age, gender, nationality and primary care
physician. Results: During 2012, 440 284 (27%) of children and adolescents had at
least one ED attendance, with trauma (26%) and respiratory tract infections (22%)
as the most frequent diagnoses. In all, 533 037 (79%) accesses were for non
urgent reasons, and 12 533 (3% of the ED users) were frequent non-urgent users.
Male gender (OR 1.12; 95% CI 1.08 to 1.17), preschool age (OR 3.14; 95% CI 2.98
to 3.31) and place of residence (OR 1.74; 95% CI 1.70 to 1.99) were associated
with a higher risk of being a frequent non-urgent user. Moreover, a greater
healthcare consumption was observed in this group. Conclusions: One out of four
children and adolescents attended the ED at least once per year, 3% of whom were
frequent non-urgent users, with a high overall healthcare resource consumption.
PMID- 29942866
TI - Demographic characteristics of labial adhesion in South Korea: a population-based
study from 2010 to 2014.
AB - Objective: To investigate the demographic features of labial adhesion (LA) in
South Korea. Design: A population-based nationwide study. Setting: Census
population of South Korea. Participants: With the entire population of South
Korea (n=47 990 761), patients under age 7 who were newly diagnosed with LA from
January 2010 to December 2014 were included. Main outcome measure: The average
incidence and the peak age of LA occurrence were estimated. Results: A total of
4934 newly diagnosed LAs were analysed. The incidence of LA has constantly
increased since 2008, the year that the Korean Developmental Screening Test for
InfantsandChildren registry began. The average incidence of LA was 55.0 cases/100
000 person-years (95% CI 53.5 to 56.6). The highest incidence was 183.6 cases/100
000 person-years (95% CI 175.8 to 191.6) in the age group of13 to 24 months. The
relative risk of acquiring LA in the age group of 13 to 24 months was 1.481 (95%
CI 1.381 to 1.587) compared with the age group of 0 to 12 months. Conclusions:
The demographic characteristics of LA including the average incidence and the
highest incidence age group in South Korea were revealed in this nationwide,
population-based study including a total of 4934 newly developed LA cases.
Further studies are needed to reveal the natural disease course and the
significance of diagnosing asymptomatic LA cases.
PMID- 29942867
TI - Drakenstein Child Health Study (DCHS): investigating determinants of early child
development and cognition.
AB - Introduction: There is growing awareness that psychosocial risk and resilience
factors in early life play a key role in influencing later health. Most work has
been done in high-income settings, rather than low-income and middle-income
countries (LMICs), where the majority of the global childhood population resides.
The few studies with well-defined cohorts in LMICs have employed various methods
and measures, making comparisons across studies challenging. This presentation
describes the methodology for infant and child developmental measures used in the
Drakenstein Child Health Study (DCHS), a multidisciplinary longitudinal birth
cohort study in South Africa. Methods and analysis: We outline a multilevel
approach combining a range of measures including parental reports, behaviour
observations, clinician-administered scales and brain imaging. Using this
approach, we aim at a longitudinal perspective of developmental, cognitive,
socioemotional and neurophysiological outcomes in a birth cohort of children in
an LMIC. Ethics and dissemination: The study was approved by the faculty of
Health Sciences, Human Research Ethics Committee, University of Cape Town
(401/2009), Stellenbosch University (N12/02/0002) and the Western Cape Provincial
Health Research committee (2011RP45). Discussion: Children in the DCHS develop in
a context typical of many communities in South Africa and other LMICs. There is a
critical need for research in LMICs to elucidate underlying factors that inform
risk for, and resilience to, poor developmental outcomes in infants born into
high-risk communities. Such work may inform effective intervention strategies
appropriate to this context.
PMID- 29942868
TI - Outcomes after injury prevention counselling in a paediatric office setting: a 25
year review.
AB - Objective: Injury is the leading cause of death and acquired disability in
children. Primary care providers routinely provide age-appropriate injury
prevention (IP) counselling during healthcare visits. The objective was to review
evaluations of the effectiveness of office-based paediatric IP counselling
research. Design: This review identified studies from July 1991 to June 2016 of
children <5 years and their caretakers to determine the effectiveness of office
based counselling on IP knowledge, behaviours and outcomes. Studies were included
if they had: (1) an intervention for a family with a child <5 years of age; (2)
an unintentional injury mechanism addressed during counselling; (3) one or more
mechanisms recommended to be discussed for children <5 years in the 2007American
Academy of Pediatrics Policy Statement; (4) counselling occurring in the office
setting; (5) an assessment of an outcome (eg, change in knowledge, behaviour or
injury occurrences); and (6) English-language publication. Study characteristics
(whether the study was controlled, randomised and/or blinded), target safety
behaviours, the sample size, outcomes assessed (injuries, behaviour changes
and/or education changes) and demonstrated effects were summarised. Results:
Sixteen articles met inclusion criteria. Twelve articles were randomised
controlled trials, three were non-randomised trials and one was a pretest and
post-test study. Fourteen articles measured a change in knowledge or reported
behaviour, four included observed behaviour change and five measured change in
injury outcomes. Thirteen of the 16 studies had positive effects demonstrated for
certain outcomes, including for fall, poisoning, burn, fire, traffic injury and
drowning prevention, while 10 showed no differences between study groups for
other outcomes. Conclusions: Published outcomes-based IP-related counselling
research in the primary care setting for young children is infrequent, and
additional research is necessary to further describe the effectiveness of these
primary prevention efforts.
PMID- 29942869
TI - Correction: CASITA: a controlled pilot study of community-based family coaching
to stimulate early child development in Lima, Peru.
AB - [This corrects the article DOI: 10.1136/bmjpo-2018-000268.][This corrects the
article DOI: 10.1136/bmjpo-2018-000268.].
PMID- 29942870
TI - Induction of lung-like cells from mouse embryonic stem cells by decellularized
lung matrix.
AB - Decellularization of tissues is a recently developed technique mostly used to
provide a 3-dimensional matrix structure of the original organ, including
decellularized lung tissues for lung transplantation. Based on the results of the
present study, we propose new utilization of decellularized tissues as inducers
of stem cell differentiation. Decellularized lung matrix (L-Mat) samples were
prepared from mouse lungs by SDS treatment, then the effects of L-Mat on
differentiation of ES cells into lung cells were investigated. ES cell derived
embryoid bodies (EBs) were transplanted into L-Mat samples and cultured for 2
weeks. At the end of the culture, expressions of lung cell-related markers, such
as TTF-1 and SP-C (alveolar type II cells), AQP5 (alveolar type I cells), and
CC10 (club cells), were detected in EB outgrowths in L-Mat, while those were not
found in EB outgrowths attached to the dish. Our results demonstrated that L-Mat
has an ability to induce differentiation of ES cells into lung-like cells.
PMID- 29942871
TI - Finding optimal mentor-mentee matches: A case study in applied two-sided
matching.
AB - Two-Sided Matching is a well-established approach to find allocations and
matchings based on the participants' preferences. While its most prominent
applications are College Admissions and School Choice problems, this paper
applies the concept to the matching of mentors to mentees in a higher education
context. Both mentors and mentees have preferences with whom they ideally want to
be matched, as well as who they want to avoid. As the general formulation for
these types of preferences is NP-hard, several existing approximation algorithms
and heuristics are compared with respect to their ability to find a matching with
desirable properties. The results show that a combination of evolutionary
heuristics and local search approaches works best in finding high-quality
solutions, allowing us to find mentor-mentee pairs which are close to the
respective ideal match.
PMID- 29942872
TI - Enhanced carbon tolerance of Ir alloyed Ni-Based metal for methane partial
oxidation.
AB - Carbon plugging of active catalytic sites significantly degrades the performance
of the hydrocarbon reformers. In this study, we show that small amount of Ir
alloyed to Ni/CeO2 nanoparticle exhibit promising improvements to the carbon
tolerance properties. XRD analysis indicates that the synthesized nanoparticles
are comprised of independent NiO and CeO2 particulates and that the added Ir
atoms tend to stay on the surface consistent with the theoretical calculation
results of the proposed Ir-Ni alloy. The Ir rich samples show higher methane
cracking rate and better carbon removal characteristics. Also, the CO selectivity
result shows that adding Ir can prolong the lifetime of the Ni active sites
despite a slight drop in the initial partial oxidization reforming rate. Our
findings highlight the enhancement effects of Ir on the Ni-based metal carbon
tolerance properties and bring us one step closer to finding a solution for the
carbon plugging problem.
PMID- 29942873
TI - Temperature and pH effect on glucose production from pretreated bagasse by a
novel species of Citrobacter and other bacteria.
AB - Cellulolytic bacteria that produce cellulases, which are active over a range of
pH and temperatures, can be used to catalyze hydrolysis of pretreated
lignocellulosic material. This is important in the production of second
generation biofuels among other biotechnological applications. In this
investigation, bacteria isolated from sugarcane bagasse were identified as
strains of Enterobacter xiangfangensis, Serratia rubidaea, Klebsiella pneumoniae
and a novel species of Citrobacter designated Citrobacter sp. UWIBGS10. The
glucose production potential of these strains was studied on thermally and
solvent pretreated sugarcane bagasse. This was performed at 24-hour intervals up
to 168 hours in the range of pH 5-9 and temperature range 25-40 degrees C.
Maximal concentrations of glucose for Citrobacter sp. UWIBGS10 occurred at pH 6
and 25 degrees C. For E. xiangfangensis, S. rubidaea, K. pneumoniae glucose
concentrations were consistent across the pH and temperature ranges examined.
From these results it could be concluded that the bacteria demonstrated ability
for lignocellulolytic hydrolysis for the production of glucose and could be
further explored for the characterization of commercial cellulolytic enzymes.
PMID- 29942874
TI - Rapid "epiretinal membrane" development following intravitreal bevacizumab for
Coats' disease.
AB - Purpose: To report a case of rapid "epiretinal membrane" ("ERM") development
following intravitreal bevacizumab for juvenile Coats' disease. Observations: A 7
year old boy was followed for four years with asymptomatic stage 2 Coats' disease
in his left eye. At age 11, he developed symptomatic cystoid macular edema. Argon
laser photocoagulation to the leaking aneurysms failed to improve his vision,
which had symptomatically declined to 20/30. Four-months after laser, a single
injection of intravitreal bevacizumab was given. Rapid development of an "ERM"
was noticed on his first post-injection follow-up at 4 weeks. By 8-weeks post
injection the visual acuity had deteriorated to 20/400. 25 + gauge pars plana
vitrectomy with "ERM" peeling was performed, with recovery of vision to 20/30 at
the 4 months post-operative visit. Conclusions and importance: Intravitreal
bevacizumab may induce rapidly progressive "ERM" in patients with juvenile Coats'
disease.
PMID- 29942875
TI - ST elevation: Differential diagnosis and caveats. A comprehensive review to help
distinguish ST elevation myocardial infarction from nonischemic etiologies of ST
elevation.
AB - Prompt diagnosis of acute ST segment elevation myocardial infarction (STEMI) by
the initial ECG is important in order to perform an urgent coronary angiography
as soon as possible and achieve successful revascularization, therewith improving
mortality and morbidity. Several diseases and conditions can mimic an acute
myocardial infarction (AMI) but may not benefit from a (percutaneous)
revascularization strategy. This narrative clinical review will discuss the ECG
features of some of the causes of non-ischemic ST segment elevation to facilitate
early recognition, prevent wrongful diagnosis and improve treatment outcomes.
PMID- 29942876
TI - How can emergency physicians protect their work in the era of pseudo publishing?
AB - Recently scientists have been targets of pseudo journals (fake, hijacked or
predatory journals). These journals provide a low barrier to publication and
quick publication times compared to high quality journals and exploit the pay-to
publish system in order to charge publication fees but they provide no formal
peer-review. We aim to increase awareness among emergency physicians about pseudo
journals. Trying to list all of fake, hijacked or predatory journals is not the
solution because new journals are launched almost everyday and the fast
proliferation of journals makes it difficult to identify and list all of them.
Only an understanding of the practices and markers of legitimate and predatory
publishers will allow the researcher to keep pace with danger because fraud is an
ever-changing field. In this review we offer basic information (our top list of
strategies and potential red flags) to recognize these journals to avoid
submission and suggest some solutions if a paper has already been submitted or
published in these journals.
PMID- 29942877
TI - Use of the iTClamp versus standard suturing techniques for securing chest tubes:
A randomized controlled cadaver study.
AB - Objectives: Tube thoracostomy (TT) is a common yet potentially life-saving trauma
procedure. After successful placement however, securing a TT through suturing is
a skillset that requires practice, risking that the TT may become dislodged
during prehospital transport. The purpose of this study was to examine if the
iTClamp was a simpler technique with equivalent effectiveness for securing TTs.
Materials and methods: In a cadaver model, a 1.5 inch incision was utilized along
the upper border of the rib below the 5th intercostal space at the anterior
axillary line. TTs (sizes 28Fr, 32Fr, 36Fr and 40Fr) were inserted and secured
with both suturing and iTClamp techniques according to the preset randomization.
TT were then functionally tested for positive and negative pressure as well as
the force required to remove the TT (pull test-up to 5 lbs). Time to secure the
TT was also recorded. Results: When sutured is placed by a trained surgeon, the
sutures and iTClamp were functionally equivalent for holding a positive and
negative pressure. Mean pull force for both sutures and iTClamp exceeded the 5 lb
threshold; there was no significant difference between the groups. Securing the
TT with the iTClamp was significantly faster (p < 0.0001) with the iTClamp having
a mean application time of 37.0 +/- 22.8 s and using a suture had a man
application time of 96.3 +/- 29.0 s. Conclusion: The iTClamp was effective in
securing TTs. The main benefit to the iTClamp is that minimal skill is required
to adequately secure a TT to ensure that it does not become dislodged during
transport to a trauma center.
PMID- 29942878
TI - Impact of point-of-care ultrasound on disposition time of patients presenting
with lower extremity deep vein thrombosis, done by emergency physicians.
AB - Background: Point-of-care venous compression ultrasound (VCU) is highly accurate
in deep vein thrombosis (DVT) diagnosis; however, waiting to perform this exam by
radiologists, may cause delay in patients' disposition. Objective: To compare the
effect of point-of-care VCU on patients' disposition time, done by emergency
physician versus radiologists. Methods: A total of 50 patients suspected of
having lower extremity DVT, were randomized into 2 equal groups and they
underwent a point-of-care VCU performed either by an emergency physician
(emergency medicine (EM) group) or a radiologist (radiology group). The mean time
of patients' disposition and management were compared between the two groups.
Results: The EM group consisted of 16 males and 9 females while the radiology
group consisted of 13 males and 12 females. The median time elapsed from triage
to performing ultrasonography and the median time elapsed from triage to final
disposition were significantly lower in the EM group than those in the radiology
group (50 min vs. 142 min, and 69 min vs. 260 min, respectively; p < .001). The
final diagnosis was confirmed to be DVT in 14 patients (56%) in the EM group and
in 17 patients (68%) in the radiology group (p = .38). There was no false
positive or negative diagnosis. Conclusions: Performing VCU in patients suspected
of having DVT by a trained emergency physician could significantly reduce the
time of patients' disposition in the emergency setting.
PMID- 29942879
TI - Placement of central venous lines for sepsis in the elderly has markedly
increased-Evidence from a cohort of New Jersey (USA) emergency departments.
AB - Background: Early goal directed therapy for sepsis patients requires placement of
central lines (CVPL) to measure central pressure. Objective: We hypothesized that
the percentage of CVPL placed for sepsis has increased over time, whereas the
frequency of lines placed for other conditions has not changed. Methods: This was
a retrospective cohort study. Investigators analyzed records from consecutive ED
patients in nine hospitals over a 10-year period. Patients >65 years identified
with CVPL by CPT codes and diagnoses established by ICD-9 codes.We computed the
annual number of patients that had a CVPL placed for sepsis and other conditions.
We calculated the change from 2005 and 2014 in the normalized number of patients
>65 with sepsis and other conditions and the 95% confidence intervals (CIs).We
normalized the annual number of CVPLs by the average number of total annual
visits for those >65 years as the annual visits in the >65 years cohort increased
by > 25% over the course of the study. We then plotted the annual number of
normalized CVPLs for sepsis and other conditions placed versus year and computed
the linear regression coefficients (R2). Alpha was set at 0.05. Results: Of the
3,772520 visits in the data base there were 711,435 visits by patients >65 years;
3184 (0.45%) had CVPL placed and 784 of those patients were treated for sepsis.
The percent of patients with CVPL for sepsis increased 212% (95% CI: 115% to
356%) from 2005 to 2014, but there was no statistically significant annual change
in percent of CVPL placed for other conditions (10% decrease, 95% CI: -26% to
9%). The linear regression coefficient for the plot of annual normalized number
of CVPLs vs. year (See table and plot) was statistically significant for sepsis
(R2 = 0.94, p < 0.001) but not for other conditions (R2 = 0.09, p = 0.80).
Conclusion: We found that CVPL placed for sepsis tripled from 2004 to 2011,
whereas CVPL placed for other conditions did not change significantly.
PMID- 29942880
TI - Grayanotoxin levels in blood, urine and honey and their association with clinical
status in patients with mad honey intoxication.
AB - Objectives: The purpose of this study was to investigate whether there is an
association between grayanotoxin levels in urine and blood of patients with mad
honey intoxication and in the honey consumed, and the resulting clinical picture.
The pilot data acquired from this study was analysed in National Forensic
Service, Daejeon Institute, South Korea and first results were published as a
preliminary study. Patients and methods: This descriptive study was conducted at
a university hospital emergency department in Turkey. 25 cases diagnosed with mad
honey intoxication were obtained the study. Samples of mad honey consumed by
patients were obtained. Blood and urine specimens were collected at presentation
to the emergency department. GTX 1 and GTX 3 levels from patients' blood, urine
and honey consumed were investigated simultaneously using the LC-MS/MS system.
Results: Mean GTX 1 concentration in blood was 4.82 ng/mL and mean GTX 3 level
6.56 ng/mL. Mean GTX concentration in urine was 0.036 MUg/mL and mean GTX 3 level
0.391 MUg/mL. Mean GTX I concentration in honeys consumed was 8.73 MUg/gr and
mean GTX 3 level 27.60 MUg/gr. Conclusion: This descriptive study is show
grayanotoxin levels in body fluids of patients with mad honey intoxication. No
association was determined between grayanotoxin levels in blood and clinical
data.
PMID- 29942881
TI - Treating acute hypertensive cardiogenic pulmonary edema with high-dose
nitroglycerin.
AB - Acute pulmonary edema due to sympathetic surge and increased peripheral vascular
resistance often present to the emergency department (ED) with markedly elevated
blood pressure, severe dyspnea, and desaturation. This condition is known as
"SCAPE" (sympathetic crashing acute pulmonary edema). We present three SCAPE
patients who were successfully treated with high-dose nitroglycerin (NTG) and
bilevel positive airway pressure (BiPAP) ventilation. All three patients
presented with respiratory failure on arrival but rapidly improved after
treatment and did not require endotracheal intubation or admission to the
intensive care unit (ICU). SCAPE patients usually present to the ED with extreme
respiratory distress associated with diaphoresis, restlessness, and high blood
pressure. Emergency physicians must know how to manage SCAPE with high-dose
nitrates and NIPPV (noninvasive positive pressure ventilation) because, when
treated promptly, one will not only save a life but also obviate the need for
endotracheal intubation and ICU admission.
PMID- 29942882
TI - Theophylline toxicity: An old poisoning for a new generation of physicians.
AB - A healthy 4-year-old female presented to the emergency department for vomiting
and diarrhea. She was diagnosed with a urinary tract infection, treated with
antibiotics and anti-emetics and discharged. Within four hours, her symptoms
recurred, followed by decreasing responsiveness and seizures. She had significant
hypokalemia, hyperglycemia, and a combined respiratory and metabolic acidosis. A
sibling then mentioned that the patient ingested their father's 200 mg sustained
release theophylline tablets the previous morning. A serum theophylline level was
immediately ordered and returned >444 MUmol/L. The patient was intubated and
treated with activated charcoal, antiemetics, potassium and intravenous fluids.
She underwent continuous renal replacement therapy and her levels declined over
the next 24 hours. She was extubated on hospital day 2 and discharged without
sequelae. Theophylline ingestions are rare but potentially very serious.
Physicians need to know how to diagnose and treat these ingestions.
PMID- 29942883
TI - Severe allergic reaction to human insulin in the patient with diabetic
ketoacidosis.
AB - Diabetic ketoacidosis (DKA) is an acute and major life-threatening complication
of diabetes mellitus. Fluid resuscitation, insulin therapy, and electrolyte
replacement are essential for DKA treatment. Rarely, life threatening allergic
reactions might develop in a patient treated with insulin. If anaphylaxis
develops after insulin, the DKA treatment options are restricted. A limited
number of case reports have been reported in patients with severe anaphylactic
reactions to human insulin who were then treated with synthetic insulin
analogues. We present a case of a 45-year-old male patient with allergic
reactions to human insulin. The patient was successfully treated with insulin
aspart and hemodialysis.
PMID- 29942884
TI - A new side effect of synthetic cannabinoid use by the bucket (waterpipe) method:
Acute respiratory distress syndrome (ARDS).
AB - The use and content of synthetic canibinden (SCs) has been rapidly increased in
the last decades. The complex content of these substances bring along a wide
spectrum of side effects. In addition to the expected neuropsychological side
effects of pleasure-inducing substances such as agitation, anxiety, panic attack
and hallucinations, rare cases of cerebrovascular diseases, seizures, acute renal
injury, myocardial infarction and chronic lung injury have also been previously
reported. Here we report a 19-year -old male who was presented with acute
respiratory distress syndrome (ARDS) within hours of inhaled SC use with the
rarely preferred bucket method. There is limited information in the literature
about pulmonary effects of SCs and we could not detect any other ARDS case that
develoed within hours after consumption of SC with the bucket method.
PMID- 29942885
TI - Ulnar sided wrist pain after falling on outstretched hand.
PMID- 29942886
TI - Use of the distal radial artery remnant for autogenous radial-cephalic wrist
fistula after radial artery harvest for coronary artery bypass grafting.
AB - Harvesting of the radial artery is a common technique used to provide conduit for
coronary artery bypass graft surgery. We report the case of a patient with
exhausted left upper extremity access options, history of left upper extremity
dialysis access-associated steal syndrome, and prior right radial artery harvest
for coronary artery bypass graft who received an autogenous distal radial artery
remnant to cephalic vein wrist fistula.
PMID- 29942887
TI - Endovascular management of an acute type B aortic dissection in a patient with
fibromuscular dysplasia.
AB - We report the case of a 44-year-old woman who developed an acute type B aortic
dissection caused by an entry tear from an aneurysmal left common iliac artery
that extended retrograde to the proximal descending thoracic aorta. She
experienced refractory chest pain despite optimal medical management, thereby
indicating repair. Endovascular aortic repair was subsequently performed.
Intraoperatively, fibromuscular dysplasia was diagnosed by the characteristic
appearance of her renal arteries. The patient tolerated the procedure and had
resolution of her chest pain. In summary, we present a highly unusual case of
type B aortic dissection resulting from a retrograde common iliac artery tear in
a patient with fibromuscular dysplasia.
PMID- 29942888
TI - Aortic arch thrombus caused by nitrous oxide abuse.
AB - Nitrous oxide is a recreational drug gaining in popularity for its deemed
innocence. However, side effects have recently been reported. In this case, a
patient suffered major aortic arch thrombus resulting in arterial occlusion of
his arm and temporary cerebral infarction and later deep venous thrombosis and
pulmonary embolism. No common causes for thrombus in this high-flow vessel were
identified. The authors state that the patient's chronic nitrous oxide abuse
might have led to this thrombus, although it has never been described previously.
This hypothesis is supported with laboratory tests at several presentations.
PMID- 29942889
TI - Acute limb ischemia of the lower extremity associated with left upper lobe
surgery for primary lung cancer.
AB - Thrombosis formation in the pulmonary vein stump after pulmonary lobectomy has
recently been reported to be an extremely rare cause of arterial embolism. We
herein report the first case series of acute limb ischemia encountered after
video-assisted thoracoscopic left upper lobectomy or left upper division
segmentectomy for primary lung cancer. The patients underwent embolectomy, and
their perioperative courses were uneventful. It should be recognized that the
pulmonary vein stump can cause acute limb ischemia after pulmonary lobectomy.
PMID- 29942890
TI - Abdominal aortic aneurysm with periaortic malignant lymphoma differentiated from
aneurysmal rupture by clinical presentation and magnetic resonance imaging.
AB - Abdominal aortic aneurysm (AAA) associated with periaortic malignant lymphoma is
difficult to differentiate from aneurysmal rupture because of similarities in
their clinical presentation and appearance on computed tomography images. We here
report a case of AAA associated with periaortic malignant lymphoma diagnosed
preoperatively with an absence of typical symptoms, showing that AAA in
periaortic malignant lymphoma can present without any clinical correlates.
Magnetic resonance imaging was used to confirm the diagnosis. The patient was
treated by endovascular repair, which may be safer and more effective than open
surgery for AAA associated with malignant lymphoma because of the tight adhesion
between the aneurysm and the lymphoid tissue.
PMID- 29942891
TI - Lower limb ischemia due to popliteal artery compression by Baker cyst.
AB - A Baker cyst is the most common mass around the knee joint. It is mostly
asymptomatic; however, it may cause knee pain or focal swelling because of
compression of vein or nerve. Herein, we report a case of Baker cyst obstructing
arterial flow and causing intermittent claudication. An attached polycystic mass
was found posterior to the popliteal artery. Needle aspiration was ineffective,
and the patient experienced recurrent lower leg pain. Surgical resection was
performed, and the patient became symptom free. Baker cyst may cause lower limb
ischemia through obstruction of arterial flow, requiring surgical intervention.
PMID- 29942892
TI - Reverse extra-anatomic aortic arch debranching procedure allowing thoracic
endovascular aortic repair of a chronic ascending aortic aneurysm.
AB - A 79-year-old woman was admitted with a large chronic dissecting ascending aortic
aneurysm starting 5 mm distal to the ostia of the left coronary artery and ending
immediately proximal to the innominate artery. A reverse extra-anatomic aortic
arch debranching procedure was performed. During the same operative time, through
a transapical approach, a thoracic stent graft was deployed with the proximal
landing zone just distal to the coronary ostia and the distal landing zone
excluding the origin of the left common carotid artery. The postoperative course
was uneventful. Computed tomography at 12 months documented patent extra-anatomic
aortic arch debranching and no evidence of endoleak.
PMID- 29942893
TI - A pararenal abdominal aortic aneurysm with iliac arteries stenosis.
PMID- 29942894
TI - Endovascular management of TransAtlantic Inter-Society Consensus D iliac artery
occlusion secondary to radiation arteritis.
AB - Management of limb ischemia caused by radiation injury can be challenging.
Atypical conduits or tunnels have been used for bypass through or around the
injured area. Application of endovascular therapy for revascularization has not
been widely published. Standard and alternative access sites with or without
hybrid arterial adjuncts can be used successfully in cases in which surgical
bypass is prohibitive. We describe a case of limb salvage in a patient treated
with high-dose radiation for recurrent endocervical adenocarcinoma using a hybrid
open surgical and endovascular approach.
PMID- 29942895
TI - Left acute neovascular glaucoma after right carotid endarterectomy.
AB - Carotid endarterectomy is a commonly performed vascular surgical procedure with
well-known complications, such as stroke and nerve injury. Neovascular glaucoma
(NVG) is an exceedingly rare complication after carotid endarterectomy that can
result in loss of vision. All previous reports of NVG after carotid
endarterectomy have occurred on the same side as the carotid surgery; in this
report, we present a case of left-sided NVG after right carotid endarterectomy
for contralateral ocular ischemic syndrome. We aim to emphasize the importance of
early recognition and treatment of this serious complication as rapid
intervention has the potential to save sight.
PMID- 29942896
TI - Transcarotid artery stenting for carotid artery pseudoaneurysm using flow
reversal technique.
AB - Carotid artery pseudoaneurysm results mostly from direct trauma, prior
endarterectomy, prior dissection, radiation, and infections. There are many
different surgical and endovascular treatment options for repair, and the choice
of treatment depends on patient-, surgeon-, and institute-related factors.
Studies have reported the efficacy of various endovascular techniques for
aneurysm repair, including stent graft placement and coil embolization, with
promising short- and long-term outcomes. In this report, we describe two cases of
carotid artery pseudoaneurysm (after trauma and after carotid endarterectomy)
treated successfully through transcarotid artery stenting using the flow reversal
technique to minimize the risk of embolization and stroke.
PMID- 29942897
TI - Aberrant splenic artery complicated by aneurysm during pregnancy.
AB - The aberrant splenic artery is an uncommon anomaly. It may become a challenging
problem when it is associated with an aneurysm diagnosed during pregnancy. Our
experience with a patient who underwent two interventions, each performed in the
postpartum period without incident, highlights the need to employ techniques that
ensure aneurysm closure and thus avoid recurrence and need for repetitive
procedures.
PMID- 29942898
TI - A mycotic aneurysm of the abdominal aorta caused by Mycobacterium bovis after
intravesical instillation with bacillus Calmette-Guerin.
AB - Intravesical administration of bacillus Calmette-Guerin (BCG), a live attenuated
strain of Mycobacterium bovis, plays an important role in adjuvant treatment of
superficial bladder cancer. Severe adverse events due to this treatment are rare.
Complications of varying character and severity have been described, including
rare BCG-related vascular infections. In this writing, we present a case of
mycotic abdominal aneurysm caused by M. bovis infection related to prior
intravesical BCG instillation.
PMID- 29942899
TI - Excision of true facial artery aneurysm using facial nerve monitoring.
PMID- 29942900
TI - A right aortic arch with abnormal origin of the left vertebral artery from the
left common carotid artery.
PMID- 29942901
TI - Abdominal aortic aneurysm and congenital pelvic kidney.
PMID- 29942902
TI - Digital gangrene and pneumatosis intestinalis associated with calciphylaxis.
AB - Reports of calciphylaxis or calcific uremic arteriolopathy associated with acral
and gastrointestinal involvement are rare. We describe a 36-year-old white woman
with end-stage renal disease on hemodialysis after failed kidney and pancreas
transplantation who developed dry gangrene of bilateral digits, osteomyelitis,
and small bowel ischemia within several months of each presentation. She had
multiple debridements of a septic right ankle. Computed tomography angiography
showed severe vascular calcification and pneumatosis intestinalis. She underwent
intestinal resection for gangrenous small bowel. A multidisciplinary approach
with aggressive medical and surgical management may improve survival. Our case
and the literature confirm the high morbidity of patients with calciphylaxis and
vascular complications. Careful follow-up remains necessary for diagnosis and
management to prevent complication, infection, and death.
PMID- 29942903
TI - Cystic adventitial disease of the popliteal artery with spontaneous regression.
AB - Cystic adventitial disease (CAD) of the popliteal artery with spontaneous
regression is rare. We describe a 44-year-old man with rapid onset of severe
intermittent claudication who is currently undergoing conservative follow-up. CAD
was diagnosed, and resection of the lesion with autologous vein replacement was
scheduled. However, the claudication suddenly improved at 5 weeks after onset.
Computed tomography and ultrasound revealed that the cystic lesion in the
adventitia had nearly disappeared. This case report describes the imaging
findings and the possibility of conservative treatment. CAD can occur in the
popliteal artery and is usually treated surgically. However, reports of
spontaneous regression are rare. We report our experience with a case of CAD that
eventually spontaneously regressed.
PMID- 29942904
TI - Migration of endovascular plug in hybrid repair of dysphagia lusoria.
AB - Aberrant right subclavian artery is the most common brachiocephalic artery
congenital abnormality and may result in dysphagia from external compression by
the aberrant artery on the esophagus. Repair of this anatomic variant can be
performed by both open and hybrid endovascular techniques. This case illustrates
a complication of a hybrid repair resulting in proximal migration of a vascular
occlusion plug, presenting as recurrent dysphagia and need for open surgical
extraction of the plug.
PMID- 29942905
TI - Coil embolization of an acutely expanding spontaneous splenic artery dissection.
AB - Symptomatic dilation of a spontaneous splenic artery dissection is a very rare
and potentially catastrophic nonatherosclerotic vascular disease. Splenic artery
rupture has not been reported after acute diffuse dilation, but it has been
reported with celiac artery dissections. We believe treatment is mandatory if
pain persists despite blood pressure control. The presentation and endovascular
treatment of a spontaneous celiac trunk dissection with continued expansion of
the splenic artery branch are discussed.
PMID- 29942906
TI - Acute aortic dissection with sporadic aortic calcifications during chemotherapy
with sunitinib.
PMID- 29942907
TI - Fenestrated endovascular repair of aortic arch aneurysm in patients with bovine
arch using the Najuta stent graft.
AB - We describe the case of a 74-year-old man with a thoracic aortic aneurysm with a
bovine arch who underwent fenestrated endovascular repair of aortic arch aneurysm
using the Najuta stent graft (Kawasumi Laboratories, Inc, Tokyo, Japan). He has
had a previous endovascular aneurysm repair and femoropopliteal bypass for
abdominal aortic aneurysm combined with peripheral arterial disease. The Najuta
stent graft was inserted and deployed at zone 0 with delicate positional
adjustment of the fenestration of the stent graft to the brachiocephalic trunk.
There was no endoleak or complication. His postoperative course was uneventful.
At 7-month follow-up, complete exclusion of the aneurysm was noted. The Najuta
stent graft repair of aortic arch aneurysms is a safe and effective treatment
option for patients with a bovine arch.
PMID- 29942908
TI - Coil embolization using microballoon assistance combined with the double-catheter
technique for a large superior mesenteric arterial pseudoaneurysm and fistula
secondary to acute pancreatitis.
AB - Pseudoaneurysm of the superior mesenteric artery (SMA) is rare and associated
with the risk of massive fatal hemorrhage and acute mesenteric ischemia. We
describe a 43-year-old man with acute pancreatitis who presented with an SMA
pseudoaneurysm measuring 13 * 12 cm in diameter. The pseudoaneurysm originated
between the first and second jejunal arteries and drained into the mesenteric
vein. The SMA trunk between the first and second jejunal arteries was embolized
with detachable coils using microballoon assistance. After coil placement,
arteriography showed the collateral circulation and no perfusion delay of the
distal SMA. This technique was useful for isolation of the SMA pseudoaneurysm.
PMID- 29942909
TI - Endovascular repair of tortuous recurrent femoral-popliteal aneurysm in a patient
with Loeys-Dietz syndrome.
AB - Loeys-Dietz syndrome is a rare connective tissue disorder with widespread
arterial tortuosity and aneurysms. This syndrome is most notable for its aortic
disease, including aortic root dilation and aortic dissection or rupture.
Although not as well studied, peripheral artery aneurysms are a prevalent
concurrent manifestation and have previously been repaired with both open and
endovascular approaches. There are minimal data about the durability and
technical considerations of endovascular repair in this disease. We report a case
of a patient who developed an extremely tortuous recurrent femoral-popliteal
artery aneurysm secondary to aneurysmal degeneration around previously placed
stents that was treated with an endovascular approach.
PMID- 29942910
TI - A case of metastatic adenocarcinoma from an unknown primary involving the aortic
bifurcation.
AB - Aortic malignant neoplasms are rare; these may be primary or secondary
(metastatic). Increasing use of cross-sectional imaging has allowed better
detection and diagnosis of these conditions. We encountered a young woman
presenting with acute abdomen who was found on cross-sectional imaging to have a
malignant tumor involving the aortic bifurcation. An en bloc excision of the
tumor was performed, with distal aorta reconstruction using an aortoiliac Dacron
graft; this was complicated with infection and graft occlusion, necessitating
total removal and extra-anatomic bypass. A pathologic diagnosis of metastatic
adenocarcinoma involving the aortic bifurcation, with an unknown primary, was
made.
PMID- 29942911
TI - Amnion membrane improves results in treating neurogenic thoracic outlet syndrome.
AB - A patient with neurogenic thoracic outlet syndrome was initially treated with
scalenectomy, first rib resection, and wrapping of the brachial plexus (BP) with
amnion membrane (AM) to prevent postoperative adhesions. Twelve months later, at
reoperation for recurrent symptoms, the AM was observed to be intact. The BP had
no scar tissue around it. Recurrence was due to scarring around the nerve roots
superior to the portion of the plexus that had been wrapped with AM. It was
concluded that the AM had successfully protected the portion of the BP that had
been wrapped. Longer term studies are in progress.
PMID- 29942912
TI - Three-vessel fenestrated and bilateral iliac branched graft repair of a
juxtarenal aortic aneurysm with bilateral common iliac aneurysms.
AB - We describe a patient with large bilateral common iliac artery aneurysms as well
as a large juxtarenal abdominal aortic aneurysm successfully treated by a novel
approach. The procedure, completed in one setting, involved this sequence:
positioning and deployment of bilateral iliac branch grafts with appropriate
internal iliac limbs; insertion of a three-vessel fenestrated proximal device
with cannulation and stenting of the left renal artery; and positioning and
deployment of a bifurcated endograft and two mating limbs to the bilateral iliac
branch device. The procedure was completed with percutaneous access; the patient
recovered well and was discharged on postoperative day 1.
PMID- 29942913
TI - Direct oral anticoagulant therapy as an alternative to surgery for the treatment
of a patient with a floating thrombus in the ascending aorta and pulmonary
embolism.
AB - A floating thrombus in the ascending aorta was incidentally discovered in a
patient with a descending thoracic aortic aneurysm and a history of alcoholism.
The patient developed deep venous thrombosis and pulmonary embolism. However, he
refused to undergo surgical excision of the thrombus in the ascending aorta.
Therefore, treatment with rivaroxaban was administered for 3 months, and it
completely dissolved the thrombus. Anticoagulant therapy may be an alternative
treatment when surgery cannot be performed.
PMID- 29942914
TI - Type IIIB endoleak caused by fabric erosion after thoracic endovascular aneurysm
repair.
PMID- 29942915
TI - Femoral vessel injury by a nonlethal weapon projectile.
AB - Rubber projectiles are used as an alternative to metal bullets owing to their
lower morbidity and mortality rate. There are few reports of vascular lesions of
extremities caused by rubber projectiles in the literature. The authors report
the case of a 37-year-old man who was the victim of a penetrating injury to the
left thigh with a rubber projectile. He reported only pain at the site of the
injury; pulses were decreased in the affected limb. After arteriography confirmed
an injury to the superficial femoral artery, he underwent an arterial and venous
femorofemoral bypass using a reversed contralateral saphenous vein.
PMID- 29942916
TI - Revascularization for failed carotid artery stenting in a patient with a rare
vertebral artery anomaly.
AB - There is a growing cohort of patients requiring complex revascularization for
failed carotid artery stenting. This revascularization can be complex in patients
with coexisting supra-aortic vascular anomalies. Aberrant origin of the vertebral
artery (VA) is an example of such an anomaly. Although VA anomalies are rare,
their occurrence is of significant importance in endovascular and open vascular
procedures. We report a case of a 78-year-old man with rare VA anomaly, whose
left internal carotid artery ostium was inadvertently covered during a carotid
artery stenting procedure. We discuss the carotid artery revascularization in
this patient as well as the relevant literature.
PMID- 29942917
TI - Endovascular treatment of complex aortic injuries 40 years after surgery for
aortic coarctation.
PMID- 29942918
TI - Extra-anatomic ascending to descending thoracic aortic bypass for repair of adult
aortic recoarctation.
PMID- 29942919
TI - Oral Glucose Tolerance Test Glucose Peak Time Is Most Predictive of Prediabetes
and Hepatic Steatosis in Obese Girls.
AB - Obese adolescent girls are at increased risk for type 2 diabetes, characterized
by defects in insulin secretion and action. We sought to determine if later
glucose peak timing (>30 minutes), 1-hour glucose >155 mg/dl, or monophasic
pattern of glucose excursion during an oral glucose tolerance test (OGTT) reflect
a worse cardiometabolic risk profile. Post-pubertal overweight/obese adolescent
girls without diabetes were studied (N = 88; age, 15.2 +/- 0.2 years; body mass
index percentile, 97.7 +/- 0.5). All participants completed an OGTT and body
composition measures. Thirty-two girls had a four-phase hyperinsulinemic
euglycemic clamp with isotope tracers, vascular imaging, and muscle mitochondrial
assessments. Participants were categorized by glucose peak timing (<=30 min =
early; >30 min = late), 1-hour glucose concentration (+/-155 mg/dL) and glucose
pattern (monophasic, biphasic). Girls with a late (N = 54) vs earlier peak (n =
34) timing had higher peak glucose (P < 0.001) and insulin (P = 0.023), HbA1c (P
= 0.021); prevalence of hepatic steatosis (62% vs 26%; P = 0.003) and lower oral
disposition index (P < 0.001) and glucagon-like peptide-1 response (P = 0.037).
When classified by 1-hour glucose, group differences were similar to peak timing,
but minimal when classified by glucose pattern. In the >155 mg/dL group only,
peripheral insulin sensitivity and fasting free fatty acids were worse. A later
glucose peak or >155 mg/dL 1-hour glucose predicts metabolic disease risk in
obese adolescent girls. This may defect incretin effects and first phase insulin
response, and muscle and adipose insulin resistance.
PMID- 29942920
TI - Suspected Testosterone-Producing Tumor in a Patient Taking Biotin Supplements.
AB - A perimenopausal woman presented with palpitations, hirsutism, and inability to
lose weight. Laboratory tests revealed an unusual endocrine hormonal profile
including pituitary hormones (TSH, ACTH, and prolactin) below reference intervals
and gonadal (testosterone) and adrenal (cortisol) hormones above reference
intervals. Ultimately, after a comprehensive workup including a scheduled
surgical procedure, abnormal laboratories were determined due to biotin
interference. Biotin (vitamin B7) is a water-soluble vitamin and essential
cofactor for the metabolism of fatty acids, glucose, and amino acids. The
recommended daily intake of biotin for adults is 30 ug/d. Many over-the-counter
products, particularly those marketed for hair, skin, and nail growth, contain
biotin 100-fold of recommended daily intake. This case is unique due to the
abnormalities observed not only in the well-described TSH "sandwich" immunoassay,
but also in tests for gonadal steroids, adrenal, and pituitary hormones. Falsely
high as well as falsely low results can be ascribed to biotin. Competitive
immunoassays (Fig. 1A)- in this case, tests used initially for serum cortisol and
testosterone- can demonstrate falsely high results. Interference falsely lowers
the immunometric "sandwich" immunoassay (Fig. 1B)-in this case, TSH. Biotin
effect on our patient's endocrine testing led to decidedly abnormal findings,
unnecessary medical referrals and diagnostic studies, and comprehensible
psychological distress. Interference with one immunoassay, TSH, persisted a full
2 weeks after discontinuation of biotin; indeed, some tests demonstrate
sensitivity to lesser quantities of biotin. Improved communication between
patients, health care providers, and laboratory professionals is required
concerning the likelihood of biotin interference with immunoassays.
PMID- 29942921
TI - Letter to the Editor: Endocrine Compromise in Mitochondrial Disorders.
PMID- 29942923
TI - Everolimus Directly Suppresses Insulin Secretion Independently of Cell Growth
Inhibition.
AB - Everolimus, an orally administered mammalian target of rapamycin inhibitor, has
been widely used as an immunosuppressant and an anticancer agent. Whereas
everolimus can control recurrent hypoglycemia in patients with insulinoma,
possibly through tumor regression and/or the direct inhibition of insulin
secretion, time-dependent changes in serum insulin levels caused by everolimus
still remain unclear. Here we report a clinical case of a patient with metastatic
insulinoma, in which frequent monitoring of serum insulin levels demonstrated
rapid and substantial changes in insulin secretion levels, a few days after the
discontinuation as well as the readministration of everolimus. To further confirm
the direct effect of everolimus on beta-cell function, we performed in vitro
experiments using mouse insulinoma cells (MIN6) and human induced pluripotent
stem cell (hiPSC)-derived insulin-producing cells and found that everolimus
significantly suppressed glucose-stimulated insulin secretion in both MIN6 cells
and hiPSC-derived insulin-producing cells. Thus, both a patient with metastatic
insulinoma and in vitro experiments demonstrated that everolimus directly
suppresses insulin secretion, independently of its tumor regression effect.
PMID- 29942922
TI - Cancer Treatment-Induced Bone Loss in Women With Breast Cancer and Men With
Prostate Cancer.
AB - Cancer and cancer therapies can have a negative impact on bone health. Because
cancer is a common diagnosis, survivorship concerns for osteoporosis and
fragility fractures are an important component of care. This review addresses
management of bone health in nonmetastatic cancer survivorship with a focus on
breast cancer and prostate cancer.
PMID- 29942924
TI - Pregnancy-Induced Perturbation of Urinary Androgenic Steroid Disposition.
AB - Objective: To investigate the excretion and conjugation profile of testosterone
(T), Epitestosterone (EpiT), and other androgen metabolites in different phases
of pregnancy and postpregnancy as a reflection of the "androgenic exposure."
Design: Consecutive recruitment of pregnant women. Setting: Maternity outpatient
low-risk pregnancy clinic. Patients: Seventy-seven pregnant women. Interventions:
Collection of urine for analyses of sulfate (S) and glucuronide (G) conjugates
and metabolic ratios of androgens and androgen metabolites using liquid
chromatography-tandem mass spectrometry. Main Outcome Measures: Excretion
profiles and metabolic ratios of G and S conjugates of T, EpiT,
dehydroepiandrosterone (DHEA), androsterone (A), etiocholanolone (Etio), and
dihydrotestosterone in relation to trimester and postpartum, body mass index,
fetal sex, and ethnicity. Results: T-S excretion increased significantly between
the second and third trimester, whereas excretion of T-G did not change. In
contrast, both conjugates of EpiT increased markedly, more so for the S-(17-fold)
than the G-conjugate (1.6-fold). The preference for S over G conjugation was
conspicuous for EpiT and DHEA (S/G ratio 2.1 and 4.7, respectively, in the third
trimester), whereas the reverse was true for T, A, and Etio (S/G 0.6, 0.13, and
0.11, respectively). Conclusions: Pregnancy influences the androgen excretion
profile, with the most profound change being an increase in EpiT excretion
throughout the trimesters. EpiT may modulate the effect of T, but its exact role
during pregnancy is not known. There were marked differences in the S/G conjugate
ratios between androgens upstream and downstream from T in the metabolic network.
These results are interesting to compare with the androgen disposition in women
with endocrine disorders or abuse of steroids.
PMID- 29942926
TI - Severe Cushing Syndrome Due to an ACTH-Producing Pheochromocytoma: A Case
Presentation and Review of the Literature.
AB - Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome is rarely caused by
a pheochromocytoma. We present a case of a 46-year-old woman who developed severe
hypertension, hypokalemia, and typical Cushingoid features. Investigations
revealed extremely high metanephrine, cortisol, and ACTH levels. Imaging showed a
3.8-cm left adrenal mass. Preoperative control of hypertension and hypokalemia
was very challenging. The patient was cured after surgical removal of the adrenal
mass. We followed this by a review of the literature using the databases Google
Scholar and PubMed. A total of 58 cases have been reported to date. In summary,
ACTH-producing pheochromocytoma is a rare condition that poses a clinical
challenge in the perioperative period. It is important that physicians be aware
of such a condition because early recognition and treatment are crucial to
decrease morbidity and mortality.
PMID- 29942925
TI - Lower Renal Function Is Associated With Derangement of 11-beta Hydroxysteroid
Dehydrogenase in Type 2 Diabetes.
AB - Context: Derangement of 11-beta hydroxysteroid dehydrogenase type 1 and type 2
(11beta-HSD1 and 11beta-HSD2), which regulate intracellular cortisol production,
has been suggested in both type 2 diabetes (T2D) and chronic kidney disease
(CKD). However, activity of 11beta-HSD enzymes in patients with T2D and CKD has
never been assessed. Objectives: To compare 11beta-HSD activities between
patients with T2D and healthy controls, and assess whether in T2D, renal function
is associated with 11beta-HSD activities. Design: Cross-sectional analysis in the
Diabetes and Lifestyle Cohort Twente (DIALECT-1). Setting: Referral center for
T2D. Patients: Patient with T2D [n = 373, age 64 +/- 9 years, 58% men, 26% of
patients estimated glomerular filtration rate (eGFR) <60 mL/min.1.73 m2] and
healthy controls (n = 275, age 53 +/- 11 years, 48% men). Mean Outcome Measure:
We measured cortisol, cortisone, and metabolites [tetrahydrocortisol (THF), allo
THF (aTHF), and tetrahydrocortisone (THE)] in 24-hour urine samples. Whole body
11beta-HSD and 11beta-HSD2 activities were calculated as the urinary (THF +
aTHF)/THE and cortisol/cortisone ratios, respectively. Results: Patients with T2D
had a higher (THF + aTHF)/THE ratio [1.02 (0.84 to 1.27) vs 0.94 (0.79 to 1.0), P
< 0.001] and cortisol/cortisone ratio [0.70 (0.58 to 0.83) vs 0.63 (0.54 to
0.74), P < 0.001] than healthy controls. In T2D, lower eGFR was associated with a
higher (THF + aTHF)/THE ratio (beta = -0.35, P < 0.001), and a higher
cortisol/cortisone ratio (beta = -0.16, P = 0.001). Conclusions: In this real
life secondary care setting of patients with T2D, 11beta-HSD enzymes activities
were shifted to higher intracellular cortisol production in T2D, which was
further aggravated in patients with CKD. Prospective analyses are warranted to
investigate causality of these associations.
PMID- 29942927
TI - Na+/Ca2+ Exchanger a Druggable Target to Promote beta-Cell Proliferation and
Function.
AB - An important feature of type 2 diabetes is a decrease in beta-cell mass.
Therefore, it is essential to find new approaches to stimulate beta-cell
proliferation. We have previously shown that heterozygous inactivation of the
Na+/Ca2+ exchanger (isoform 1; NCX1), a protein responsible for Ca2+ extrusion
from cells, increases beta-cell proliferation, mass, and function in mice. Here,
we show that Ncx1 inactivation also increases beta-cell proliferation in 2-year
old mice and that NCX1 inhibition in adult mice by four small molecules of the
benzoxyphenyl family stimulates beta-cell proliferation both in vitro and in
vivo. NCX1 inhibition by small interfering RNA or small molecules activates the
calcineurin/nuclear factor of activated T cells (NFAT) pathway and inhibits
apoptosis induced by the immunosuppressors cyclosporine A (CsA) and tacrolimus in
insulin-producing cell. Moreover, NCX1 inhibition increases the expression of
beta-cell-specific genes, such as Ins1, Ins2, and Pdx1, and
inactivates/downregulates the tumor suppressors retinoblastoma protein (pRb) and
miR-193a and the cell cycle inhibitor p53. Our data show that Na+/Ca2+ exchange
is a druggable target to stimulate beta-cell function and proliferation. Specific
beta-cell inhibition of Na+/Ca2+ exchange by phenoxybenzamyl derivatives may
represent an innovative approach to promote beta-cell regeneration in diabetes
and improve the efficiency of pancreatic islet transplantation for the treatment
of the disease.
PMID- 29942928
TI - PAPPA2 as a Therapeutic Modulator of IGF-I Bioavailability: in Vivo and in Vitro
Evidence.
AB - Context: Pregnancy-associated plasma protein A2 (PAPPA2) is a protease that
cleaves IGF-binding protein (IGFBP)-3 and IGFBP-5, liberating free IGF-I. Five
patients from two families with genetic mutations in PAPPA2 presented with growth
retardation, elevated total IGF-I, and IGFBP-3 but decreased free IGF-I.
Objective: To determine whether plasma transfusion or recombinant human
(rh)PAPPA2 could increase free IGF-I in patients with PAPPA2 deficiency or
idiopathic short stature (ISS). Design: Single patient interventional study
combined with in vitro experimentation. Setting: Academic medical center.
Patients: Three siblings with PAPPA2 deficiency and four patients with ISS.
Interventions: An adult female with PAPPA2 deficiency received a 20 mL/kg plasma
transfusion. PAPPA2, intact IGFBP-3, and free and total IGF-I levels were
monitored during 2 weeks. rhPAPPA2 was added to serum from patients with PAPPA2
deficiency and ISS in vitro for 4 hours. Intact IGFBP-3 and free IGF-I levels
were assayed via ELISA. Main Outcome Measures: Free IGF-I concentrations.
Results: Plasma transfusion resulted in a 2.5-fold increase of free IGF-I levels
on day 1 posttransfusion with a return to baseline during a 2-week period. In
vitro studies demonstrated a dose-dependent increase in free IGF-I and decrease
in intact IGFBP-3 after the addition of rhPAPPA2. The increase in free IGF-I was
more pronounced in patients with PAPPA2 deficiency compared with those with ISS.
Conclusions: PAPPA2 plays a key role in regulation of IGF-I bioavailability.
rhPAPPA2 is a promising therapy to increase free IGF-I levels both in patients
with PAPPA2 deficiency as well as in patients with ISS.
PMID- 29942930
TI - Prevalence, causes, and complications of cesarean delivery in Iran: A systematic
review and meta-analysis.
AB - Background: Uncontrolled increase of C-section is one of the major problems in
Iranian health system, such that C-section is the most common surgical procedure
in the entire country's hospitals in Obstetrics and Gynecology sections. A
variety of complications also come along with cesarean. Objective: The aim of
this study was to evaluate the prevalence, causes, and complications of cesarean
in Iran. Materials and Methods: forty-one articles were considered with respect
to certain criteria and were included in a systematic review to perform a meta
analysis study. The systematic review's search was conducted on SID, Iranmedx,
Magiran, Medlib, PubMed, and Science Direct databases published between1999-2016.
The weight of each included study was calculated according to its sample size and
the reported prevalence of binomial distribution. A random-effects model using R
and STATA (Version 11.2) software was utilized for analyzing data. Results: The
total number of the sample was 197514 pregnant women with a mean age of 26.72 yr.
The prevalence of cesarean in Iran was estimated at 48%. The main reasons for the
prevalence of cesarean in this study were mothers' higher education, previous
cesarean, and doctor recommendation. The most frequent complication in women
undergoing cesarean was the muscular pain, and the most common fetal
complications in newborns by caesarean delivery was transient tachypnea.
Conclusion: The prevalence of C-section in Iran is much higher than what WHO
recommends. It is essential, to decrease such a phenomenon, making the mothers
aware of the risks of cesarean delivery, and establishing counselling sessions as
well to eliminate the mothers' fear of vaginal delivery.
PMID- 29942929
TI - Fibroblast Growth Factor 2 and Its Receptors in Bone Biology and Disease.
AB - The fibroblast growth factor (FGF) regulatory axis is phylogenetically ancient,
evolving into a large mammalian/human gene family of 22 ligands that bind to four
receptor tyrosine kinases for a complex physiologic system controlling cell
growth, differentiation, and metabolism. The tissue targets for the primary FGF
function are mainly in cartilage and in bone for morphogenesis, mineralization,
and metabolism. A multitude of complexities in the FGF ligand-receptor signaling
pathways have made translation into therapies for FGF-related bone disorders such
as osteomalacia, osteoarthritis, and osteoporosis difficult but not impossible.
PMID- 29942931
TI - Testicular histopathology and phosphorylated protein changes in mice with
diabetes induced by multiple-low doses of streptozotocin: An experimental study.
AB - Background: The streptozotocin (STZ)-induced diabetic model is widely used to
evaluate the adverse effects of diabetes mellitus (DM) on spermatogenesis and
testicular steroidogenesis. However, the actual mechanism of sub/infertility in
DM males needs to be elucidated. Objective: To conduct a detailed examination of
the testicular histopathology, sperm acrosome reaction (AR) status, and tyrosine
phosphorylated protein expression in the testis of male mice induced with STZ.
Materials and Methods: Ten ICR mice were divided into two groups (n=5/each):
control and diabetes induced by multiple low doses of streptozotocin (MLD-STZ).
The control mice were intraperitoneally injected with citrate buffer, whereas MLD
STZ mice were injected with STZ at 40 mg/kg body weight for five consecutive
days. At the end of the experiment (day 40), reproductive parameters, AR status,
and the histopathology of the testis and epididymis were evaluated. The
expression of testicular tyrosine phosphorylated proteins was examined. Results:
Blood glucose levels, AR percentages, and sperm abnormality of STZ group were
significantly higher (p=0.003, 0.001, 0.000), while sperm concentration was
significantly lower (p=0.001) compared to control. Histopathology of the
seminiferous tubule was classified into 7 types. Additionally, abundant round
cells were found in the epididymal lumen of the MLD-STZ mice. Moreover, the
intensities of testicular phosphorylated proteins (170, 70, 36, 30, and 25 kDas)
were markedly higher and a 120 kDa protein band was noticeably lower in the MLD
STZ mice. Conclusion: MLD-STZ-induced DM causes many testicular histopathologies,
precocious sperm AR, and increased expression of testicular phosphorylated
proteins. These findings may clarify some mechanisms of sub/infertility in DM
males.
PMID- 29942932
TI - NFKB1 rs28362491 and pre-miRNA-146a rs2910164 SNPs on E-Cadherin expression in
case of idiopathic oligospermia: A case-control study.
AB - Background: A notable proportion of idiopathic male infertility cases is
accompanied by oligozoospermia; and yet, the molecular mechanisms of
fertilization problem underlying this defect are still unclear. Epithelial
cadherin has been involved in several calcium-dependent cell-to-cell adhesion
events; however, its participation in gamete interaction has also not been fully
investigated. Objective: The aim was to investigate the changes in the expression
of E-cadherin, based on the frequency of Single nucleotide polymorphisms in
Nuclear Factor Kappa-B 1 and pre-mir-146a in oligospermic men. Materials and
Methods: In this case-control study, semen and blood samples of 131 oligospermic
men as the case group and 239 fertile healthy men as the control group were
analyzed. Variants single nucleotide polymorphisms rs28362491 and rs2910164 were
performed using polymerase chain reaction-restriction fragment length
polymorphism method and E-cadherin expression were determined by
immunoprecipitation studies. Results: ins/ins genotype of rs28362491 was
determined as a risk factor for idiopathic oligospermia by 1.73 times (p=0.0218),
whereas no significant differences were found between the groups concerning pre
mir-146a rs2910164 polymorphism (p=0.2274 in case of GC genotype and p=0.9052 in
case of GG genotype). Combined genotype analysis results did not show any notable
differences between the multiple comparisons of 28362491-rs2910164 in
oligospermic men and control groups. In addition, E-cadherin expression of
oligospermic men with ins/ins genotype was significantly lower than patients with
del/ins genotype (p=0.0221). E-cadherin expression level was low in oligospermic
men with respect to the control group in presence of ins/ins genotype of NFKB1
gene. Conclusion: These results suggest that ins allele prevents binding of
surface proteins to spermatozoa, leading to a low affinity of sperm-oocyte
interaction in oligospermic men.
PMID- 29942933
TI - Pregnancy outcome in delayed start antagonist versus microdose flare GnRH agonist
protocol in poor responders undergoing IVF/ICSI: An RCT.
AB - Background: Over the years, many article on different aspects of pathogenesis and
management of poor ovarian responders have been published but there is no clear
guideline for treating themyet. Objective: This study was designated to compare
the effectiveness of a delayed start protocol with gonadotropin-releasing hormone
(GnRH) antagonist and microdose flare-up GnRH agonist protocol in poor ovarian
responders. Materials and Methods: This randomized clinical trial consisted of
100 poor ovarian responder women in assisted reproductive technologies cycles.
They were divided randomly in delayed-start antagonist protocol (with estrogen
priming followed by early follicular-phase GnRH antagonist treatment for 7 days
before ovarian stimulation) and microdose flare-up GnRH agonist protocol. The
main outcome was clinical pregnancy rate and second outcome was the number of
retrieved oocytes, mature oocytes, 2PN number, fertilization rate, and
implantation rate. Results: Fertilization rate, clinical pregnancy rate, and
ongoing pregnancy rates were not significantly different between the two studied
protocols. Number of retrieved oocytes (5.10+/-3.41 vs. 3.08+/-2.51) with
p=0.002, mature oocytes (4.32+/-2.69 vs. 2.34+/-1.80) with p=0.003, number of 2PN
(3.94+/-1.80 vs. 2.20+/-1.01) with p=0.001 and implantation rate (19.40% vs.
10.30%) with p=0.022 were significantly higher in delayed antagonist group.
Conclusion: The delayed-start protocol can improve ovarian response in poor
responders by stimulating and synchronizing follicle development.
PMID- 29942934
TI - Protective effect of cerium oxide nanoparticle on sperm quality and oxidative
damage in malathion-induced testicular toxicity in rats: An experimental study.
AB - Background: Malathion is an organophosphorus pesticide that commonly used in many
agricultural and non-agricultural processes. Previous studies have reported the
effects of melatonin on the reproductive system. Cerium dioxide nanoparticles
(CeNPs) due to their antioxidative properties are promising to impact on the
development of male infertility. Objective: The aim of this study was to evaluate
the effect of CeNPs on oxidative stress and sperm parameters after malathion
exposure of male rats. Materials and Methods: 36 adult male Wistar rats were
divided into 6 groups (n=6/each): Control, CeNPs -treated control (15 and 30
mg/kg/day), malathion (100 mg/ kg/day), and CeNPs -treated malathion groups (15
and 30 mg/ kg/day). At the end of the study (4 wk), the sperm counts, motility,
and viability in the testis of rats were measured, also lipid peroxidation, total
antioxidant capacity, and total thiol groups in homogenate testis were
investigated. Results: Malathion significantly reduced sperm count, viability,
and motility than the control rats (p<0.001). Co-treatment of malathion with
CeNPs 30 mg/kg had a protective effect on sperm counts (p=0.03), motility
(p=0.01), and viability (p<0.001) compare to malathion group. Also, the results
showed that malathion reduced testis total anti-oxidant capacity, the total thiol
group, and increased testis malondialdehyde than the control rats (p<0.001).
CeNPs 30 mg/kg are increased total antioxidant capacity (p<0.001) and total thiol
group (p=0.03) compared to malathion group. CeNPs at both doses (15 and 30 mg/kg)
improved malondialdehyde than the malathion group (p<0.001 and p=0.01
respectively). Conclusion: CeNPs 30 mg/kg administered considerably restored
testicular changes induced by malathion. The improvement of oxidative stress by
CeNPs may be associated with increased sperm counts, motility and viability in
the testis.
PMID- 29942935
TI - Ovary stereological features and serum biochemical factors following induction of
polycystic ovary syndrome with testosterone enanthate in mice: An experimental
study.
AB - Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder featured by
insulin resistance and hyperandrogenism. Testosterone enanthate can induce PCOS
in mice models. Objective: We investigated the ovary stereological features along
with the oxidative stress and inflammatory factors in mice following PCOS
induction using testosterone enanthate. Materials and Methods: Twelve female NMRI
mice (3 wk old) were divided into 2 groups (n=6/each): Control and PCOS. PCOS was
induced through daily injections of testosterone enanthate (1 mg/100g
subcutaneous s.c for 5 wk). Finally, ovaries were studied stereologically. The
serum levels of the follicle-stimulating hormone, luteinizing hormone,
testosterone, interleukin-6, and tumor necrosis factor-alpha were measured using
ELISA kit. Serum levels of Malondialdehyde and the antioxidant capacity were
measured relatively using thiobarbituric acid and ferric reducing antioxidant
power assay. Results: The mean total volume of ovary and the mean volume of
cortex (p<0.001), volume of oocyte in the preantral (p=0.011) and antral follicle
(p=0.015), thickness of zona pellucida (p=0.016), the number of antral follicles
(p=0.012), the serum levels of follicle-stimulating hormone (p<0.001) and the
antioxidant capacity (p=0.020) reduced significantly in the PCOS group compared
to the control. The number of primary (p=0.017) and preantral (p=0.006) follicles
and the serum levels of testosterone (p<0.001), Luteinizing hormone (p=0.002),
Malondialdehyde, Interleukin 6 and Tumor necrosis factor-alpha (p<0.001) showed a
significant increase in the PCOS group compared to the control. Conclusion:
Testosterone enanthate induced PCOS causes stereological features in the ovary,
increases the oxidative stress and inflammatory markers in mice.
PMID- 29942936
TI - Thymoquinone ameliorates some endocrine parameters and histological alteration in
a rat model of polycystic ovary syndrome.
AB - Background: Polycystic ovary syndrome (PCOS) is a common form of the endocrine
disease which is associated with metabolic dysfunction. PCOS and type 2 diabetes
mellitus are related in multiple aspects and are similar in many pathological
features. Anti-diabetic effects of Nigella sativa and protective effects of it on
reproductive system have been suggested in some reports. Objective: The aim of
current study was to evaluate the effects of thymoquinone, the main components of
Nigella sativa, on PCOS model of rats. Materials and Methods: Intraperitoneal
injection of estradiol valerate for 25 days was used to induce PCOS in Wistar
rats, followed by intraperitoneal administration of 8 and 16 mg/kg thymoquinone
for 30 days. Rats were divided into 5 groups; control, sham or PCOS, experiment-1
(PCOS and 8 mg/kg thymoquinone), experiment-2 (PCOS and 16 mg/kg thymoquinone),
and metformin (PCOS and metformin administration, 100 mg/kg) groups. All of the
animals were subjected to serum biochemical analysis of blood and
histopathological study of ovaries. Results: Estradiol valerate induced PCOS
while administration of thymoquinone recovered it. The body weight, ovarian
morphology, and ovulation had been improved and the serum biochemical parameters
including glucose, triglyceride, total cholesterol, low-density lipoprotein, high
density lipoprotein, luteinizing hormone, and follicle stimulating hormone were
reversed after thymoquinone intervention. Conclusion: Our data suggest that
thymoquinone has improvement effects on an ovarian function and ovulation in the
PCOS rat model. Therefore, thymoquinone and Nagilla sativa could be used as a
protective agent and as an adjunct treatment in PCOS patients.
PMID- 29942937
TI - Male obesity and semen quality: Any association?
AB - Background: Infertility as well as obesity are risng global concern. Whilst there
is an established association between female obesity and infertility, a similar
link is yet to be proven in men. Objective: To determine the effects of elevated
body mass index (BMI) on semen quality among male partners of infertile couples
attending an infertility clinic. Materials and Methods: In this cross-sectional
study, 206 men who met the inclusion criteria were recruited for the study.
Selected participants were grouped according to their BMI (kg/m2): normal BMI
(18.5-24.9 kg/m2) and elevated BMI (>=25 kg/m2). The effect of weight on semen
quality was assessed based on sperm count, percentage motility, and morphology.
Results: The number of participants with normal BMI was 110 (53.4%) while those
with elevated BMI were 96 (46.6%). Of the participants in elevated BMI group, 52
(25.2%) were overweight and 44 (21.4%) were obese. There was no statistically
significant difference in the semen quality as well as the pattern of semen
parameter abnormalities between males with normal and elevated BMI (overweight or
obese) (p=0.813). Conclusion: Elevated BMI did not significantly influence semen
quality.
PMID- 29942938
TI - Oxygen activation at a dicobalt centre of a dipyridylethane naphthyridine
complex.
AB - The mechanism of oxygen activation at a dicobalt bis-MU-hydroxo core is probed by
the implementation of synthetic methods to isolate reaction intermediates.
Reduction of a dicobalt(iii,iii) core ligated by the polypyridyl ligand
dipyridylethane naphthyridine (DPEN) by two electrons and subsequent protonation
result in the release of one water moiety to furnish a dicobalt(ii,ii) center
with an open binding site. This reduced core may be independently isolated by
chemical reduction. Variable-temperature 1H NMR and SQUID magnetometry reveal the
reduced dicobalt(ii,ii) intermediate to consist of two low spin Co(ii) centers
coupled antiferromagnetically. Binding of O2 to the open coordination site of the
dicobalt(ii,ii) core results in the production of an oxygen adduct, which is
proposed to be a dicobalt(iii,iii) peroxo. Electrochemical studies show that the
addition of two electrons results in cleavage of the O-O bond.
PMID- 29942942
TI - Electromechanical failure of MoS2 nanosheets.
AB - Molybdenum disulfide (MoS2) has attracted particular attention as a promising
electronics and optoelectronics material due to its significant physical
properties. In this research, the electromechanical properties of MoS2 nanosheets
are systematically investigated with the conductive AFM nanoindentation method.
The suspended MoS2 nanosheets with the thickness of tens of nanometers can
sustain external applied load (~4.3 MUN) until the bias increases to a critical
value (+4 V). Small external load (~400 nN) may also lead to a failure when the
bias (+7 V) overcomes the contact Schottky barrier and generates high electric
current. The extent of destruction of MoS2 nanosheets is related to the external
applied load and the bias. Besides, the MoS2 nanosheets suspended on the holes
are more likely to be damaged than those supported on the substrate under the
same conditions. The volcanic volume expansion profiles of the damaged area after
the electromechanical failure are caused by electric current-induced local
heating anodic oxidation and buckling-induced structural instability. The
emergence of gas bubbles in the damaged area proves the strong oxidation process.
These experiments have proved that the electric current can promote the
mechanical failure of MoS2 nanosheets. The findings can also provide beneficial
guidance for the electromechanical applications of MoS2 nano-devices.
PMID- 29942943
TI - Surface acoustic wave diffraction driven mechanisms in microfluidic systems.
AB - Acoustic forces arising from high-frequency surface acoustic waves (SAW) underpin
an exciting range of promising techniques for non-contact manipulation of fluid
and objects at micron scale. Despite increasing significance of SAW-driven
technologies in microfluidics, the understanding of a broad range of phenomena
occurring within an individual SAW system is limited. Acoustic effects including
streaming and radiation force fields are often assumed to result from wave
propagation in a simple planar fashion. The propagation patterns of a single SAW
emanating from a finite-width source, however, cause a far richer range of
physical effects. In this work, we seek a better understanding of the various
effects arising from the incidence of a finite-width SAW beam propagating into a
quiescent fluid. Through numerical and experimental verification, we present five
distinct mechanisms within an individual system. These cause fluid swirling in
two orthogonal planes, and particle trapping in two directions, as well as
migration of particles in the direction of wave propagation. For a range of IDT
aperture and channel dimensions, the relative importance of these mechanisms is
evaluated.
PMID- 29942944
TI - Amaranth peptides decreased the activity and expression of cellular tissue factor
on LPS activated THP-1 human monocytes.
AB - The effect of amaranth peptides on the activity and expression of tissue factor
(TF) on THP-1 activated cells was evaluated in vitro. An active anticoagulant
peptide fraction (AF) was found to inhibit TF expression (IC50 = 0.39 mg mL-1)
and activity. Immunocytochemical fluorescence confocal microscopy analysis showed
that treated monocytes decreased TF membrane translocation by 49.0% and increased
two-fold in nuclei compared to a positive control, indicating a decrease of
active TF to initiate the coagulation cascade. Moreover, a cytokine array
suggested that the AF mechanism of action implied the inhibition of the NF-kappaB
pathway. Expression of MIP-3alpha, interleukin-1beta, interleukin-1alpha, TARC,
pentaxin 3, and PDGF-AA cytokines was highly suppressed by AF peptides, producing
reductions of 78.8%, 61.8%, 54.1%, 42.6%, 37.9% and 37.8%, respectively, compared
to a positive control. The results suggest a potential mechanism for the
antithrombotic and anti-inflammatory effect of AF, by showing that amaranth
peptides play a negative feedback regulatory role over the NF-kappaB pathway. In
this research, we link for the first time the immunomodulatory activity of
amaranth peptides with the inhibition of TF expression and therefore their
antithrombotic potential.
PMID- 29942945
TI - Cyclooctatetraenyl calcium and strontium amido complexes.
AB - This paper reports the synthesis and structural characterisation of a series of
cyclooctatetraenyl (C8H8) complexes of calcium and strontium, most of them
containing the bis(trimethylsilyl)amido ligand. Mixing MI2 (M = Ca, Sr),
KN(SiMe3)2 and K2(C8H8) in thf in a 2 : 2 : 1 ratio gave the inverse sandwich
amido complexes [[{(Me3Si)2N}M(thf)x]2(MU-C8H8)] (M = Ca, x = 1; M = Sr, x = 2)
(1-Ca, 1-Sr) in fair to good yields. From a 1 : 1 : 1 ratio, the mixed potassium
calcium complex [[{(Me3Si)2N}Ca(thf)](MU-C8H8)K] (2) was obtained in good yield.
The reaction of 2 with a 1 : 1 mixture of CaI2 and KN(SiMe3)2 yielded 1-Ca
confirming that the reaction could be carried out stepwise. Attempts at making
heterobimetallic calcium strontium amido complexes from the reaction of 2 with
Sr{N(SiMe3)2}2 led to redistribution reactions which afforded the potassium
strontium complex [[K{(Me3Si)2N}2Sr]2(MU-C8H8)] (3) among other species. Complex
3 was more conveniently synthesised in fair yield starting from a 2 : 4 : 1 molar
mixture of SrI2, KN(SiMe3)2 and K2(C8H8), respectively. Treatment of 2 with
PhC[triple bond, length as m-dash]CH in benzene yielded an insoluble complex
tentatively formulated as the polymeric complex [CaK(CCPh)(C8H8)(thf)x]n (4).
Upon dissolution in thf, 4 underwent a redistribution reaction yielding the X-ray
characterised [{Ca(MU-C8H8)2}K2(thf)2] (5) and a homoleptic calcium alkynyl
complex [Ca(CCPh)2(thf)x]. Several compounds were characterised by X-ray
diffraction as discrete or polymeric structures where CaCpi interactions were
identified in some cases. Despite identified drawbacks, such as the lability of
the coordinated thf ligands and facile redistribution reactions, this study
represents the first synthetic approach to cyclooctatetraenyl heavy alkaline
earth metal amido complexes.
PMID- 29942946
TI - Synthesis and structure of arylselenium(ii) and aryltellurium(ii) cations based
on rigid 5-tert-butyl-1,3-bis-(N-pentylbenzimidazol-2'-yl)benzenes.
AB - The transmetalation reactions of a mercury precursor, [Pentyl(N^C^N)HgCl] (19),
with selenium halides (SeCl4, SeBr4, and SeCl2) were attempted to obtain the
corresponding organoselenium trichloride [Pentyl(N^C^N)SeCl3], tribromide
[Pentyl(N^C^N)SeBr3], and monochloride [Pentyl(N^C^N)SeCl], respectively [(N^C^N)
= 5-tert-butyl-1,3-bis-(N-pentyl-benzimidazol-2'-yl)phenyl]. However, in all the
cases, a very facile ionization of the Se-halogen bond was observed leading to
the isolation of a new class of air stable arylselenium(ii) complexes:
[Pentyl(N^C^N)Se+]2[HgCl4]2- (20) and [Pentyl(N^C^N)Se+]2[HgBr4]2- (21). This is
the first report on the formation of NCN pincer-based arylselenium(ii) cations
via the transmetalation route. Similar reactions were further investigated with
several tellurium precursors: {TeCl4, TeBr4 and TeI2} which resulted in the
formation of analogous aryltellurium(ii) complexes: [Pentyl(N^C^N)Te+]2[HgCl4]2-
(22), [Pentyl(N^C^N)Te+][Cl]- (23), [Pentyl(N^C^N)Te+]2[HgBr4]2- (24),
[Pentyl(N^C^N)Te+][Br]- (25) and [Pentyl(N^C^N)Te+]4[Hg2Cl4.72I3.28]4- (26).
These are only the second set of examples of aryltellurium cations (hypervalent
10-Te-3 species) with the NCN pincer-based ligand, characterised by X-ray
crystallographic studies. The crystallographic studies show a strong SeN/TeN
intramolecular interaction, which is confirmed by NBO calculations suggesting the
donation of a lone pair of electrons on nitrogen to a lone p-vacancy on
selenium/tellurium atoms. The analysis based on NPA derived charges indicates
that the contribution of SeN interactions to the electrostatic stabilization
energy is in the range of 40-60%, whereas TeN interactions have a contribution of
about 84% and more, attributed to the differences in the electronegativity of
selenium and tellurium. Furthermore, the formation of arylselenium(ii) and
aryltellurium(ii) complexes was favoured due to the presence of the sigma-hole on
the Se/Te centres.
PMID- 29942947
TI - Atomic layer deposition of TiO2 shells on MoO3 nanobelts allowing enhanced
lithium storage performance.
AB - Atomic layer deposition (ALD) of TiO2 shells on MoO3 nanobelts (denote as
TiO2@MoO3) is realized using a home-made ALD system, which allows a controllable
hydrolysis reaction of TiCl4-H2O on an atomic scale. When used as an anode
material for lithium ion batteries, the TiO2@MoO3 electrode demonstrates much
enhanced lithium storage performance including higher specific capacity, better
cycling stability and rate capability.
PMID- 29942948
TI - PredCSO: an ensemble method for the prediction of S-sulfenylation sites in
proteins.
AB - Protein S-sulfenylation is a type of reversible post-translational modification
(PTM) through which cysteine (CYS) thiols of proteins are reversibly oxidized to
cysteine sulfenic acids (CSO). Recent studies have shown that this event plays an
essential role in cell signaling, transcriptional regulation and protein
functions. Therefore, the identification of S-sulfenylation sites is important to
understand the functions of S-sulfenylated proteins. In this study, we proposed
PredCSO, a computational method for predicting S-sulfenylation sites in proteins.
PredCSO is built on four kinds of features, including position-specific scoring
matrix, position-specific amino acid propensity, the absolute solvent
accessibility and four-body statistical pseudo-potential. In particular, 21
crucial features were refined out using a two-step feature selection procedure
consisting of a max-relevance algorithm and a sequential backward elimination
algorithm. To overcome the problem of imbalanced sample sizes, we adopt an
ensemble method, which combines bootstrap resampling, gradient tree boosting and
majority voting. Our performance evaluation shows that PredCSO achieves state-of
the-art performance in identifying S-sulfenylation sites in proteins.
PMID- 29942949
TI - Low molecular weight heparin-based reduction-sensitive nanoparticles for
antitumor and anti-metastasis of orthotopic breast cancer.
AB - Tumor metastasis has become a major obstacle for the clinical treatment of
malignant breast cancer. Thus, a delivery system capable of both antitumor and
anti-metastasis efficacy is desired. In this work, a low molecular weight heparin
(LMWH)-based reduction-sensitive delivery system was developed, aiming to combine
the properties of both the antitumor drug and active excipients to achieve a
synergistic antitumor and anti-metastatic efficiency as well as resolving the
potential adverse effects of both doxorubicin and LMWH. That is, the efficiency
of DOX could be enhanced and its toxicity could be lowered. Meanwhile, the
biological properties of LMWH could be strengthened and its bleeding risk could
also be alleviated. Briefly, drug-loaded crosslinked nanoparticles (DOX/cLLHC2)
had a longer blood circulation time and exhibited a rapid reduction-triggered
release of DOX. The in vitro assays revealed that DOX/cLLHC2 exhibited a higher
cellular uptake and cytotoxicity compared to free DOX. Meanwhile, for the
existence of LMWH, DOX/cLLHC2 inhibited cell migration and invasion, as well as
effectively inhibited the tube-like formation of human umbilical vein endothelial
cells. DOX/cLLHC2 possessed a superior tumor accumulation compared to lipoic acid
unmodified nanoparticles and free DOX. Also, DOX/cLLHC2 exhibited encouraging
antitumor and anti-metastasis efficiency in an orthotopic breast cancer model.
Overall, DOX/cLLHC2 could exert antitumor, anti-metastasis, and anti-angiogenesis
efficacy simultaneously as well as having lower systemic toxicity, which makes it
suitable for the therapy of metastatic breast carcinoma.
PMID- 29942950
TI - Fe-doped CoP nanosheet arrays: an efficient bifunctional catalyst for zinc-air
batteries.
AB - It is highly desired to design and develop low-cost and efficient bifunctional
electrocatalysts for zinc-air batteries (ZABs). In this communication, we report
that Fe-doped CoP nanosheet arrays on nickel foam (Fe0.33-CoP/NF) act as a highly
active bifunctional electrocatalyst for both the oxygen reduction reaction and
the oxygen evolution reaction in alkaline media. We further demonstrate the use
of Fe0.33-CoP/NF as the cathode to construct rechargeable ZABs with superior
performance to that of the CoP/NF counterpart. In concentrated alkaline
electrolytes, such ZABs exhibit a higher power density of 63 mW cm-2 than that of
CoP/NF (23 mW cm-2) with a long cycle life (up to 200 h).
PMID- 29942952
TI - Enhanced electrochemical performance of Na0.5Ni0.25Mn0.75O2 micro-sheets at 3.8 V
for Na-ion batteries with nanosized-thin AlF3 coating.
AB - Na0.5Ni0.25Mn0.75O2 (NNMO) micro-sheets are novel and attractive cathode
materials for Na-ion batteries because of the high capacity and a considerable
operating voltage of 3.8 V versus Na/Na+, while the rate and cycling capabilities
were not satisfactory. In this paper, AlF3 and Al2O3 were employed as surface
modifying materials to enhance the electrochemical performance of NNMO micro
sheets by a simple wet chemical process. XRD, SEM and TEM analyses indicated that
the AlF3 layer was amorphous and evenly coated on the surface of NNMO, while the
Al2O3 layer was attached to the NNMO surface with the morphology of
nanoparticles. Different coating modes led to different electrochemical results.
AlF3 coated NNMO (NNMO@AlF3) delivered a better rate and cycling performance than
the pristine NNMO, while the Al2O3 coated NNMO (NNMO@Al2O3) could not. The
NNMO@AlF3 exhibited a 1C discharge capacity of 108 mA h g-1 and 0.2C capacity
retention of 80% up to 100 cycles with the almost invariable high potential. The
electrochemistry impedance spectroscopy analysis demonstrated that the AlF3
coated NNMO had the best structure stability and fastest Na-intercalation
kinetics.
PMID- 29942954
TI - Pd/C-catalyzed dehydrogenation of 2-cinnamoylbenzoic acids to 3-benzylidene-3H
isochroman-1,4-diones.
AB - Pd/C, a widely accepted hydrogenation catalyst, is found to catalytically
dehydrogenate 2-cinnamoylbenzoic acids to 3-benzylidene-3-H-isochroman-1,4-diones
with H2 as the only byproduct. This synthetic reaction proceeds without oxidants
and hydrogen acceptors, thereby representing an atom- and step-efficient approach
to a wide range of functionalized 3-benzylidene-3H-isochroman-1,4-diones.
PMID- 29942955
TI - Enhanced Schottky effect of a 2D-2D CoP/g-C3N4 interface for boosting
photocatalytic H2 evolution.
AB - As emerging noble metal-free co-catalysts, transition metal phosphides have been
employed to improve photocatalytic H2 production activity. Herein, the
metallicity of CoP, as a representative phosphide, and the Schottky effect
between CoP and g-C3N4 are confirmed via theoretical calculations. Then, a 2D/2D
structure is designed to enlarge the Schottky effect between the interfaces, for
which the apparent quantum efficiency of the photocatalytic H2 evolution is 2.1
times that of corresponding 0D/2D heterojunctions. The morphology,
microstructure, chemical composition, and physical nature of pristine CoP, g
C3N4, and the composites are characterized in order to investigate the dynamic
behavior of photo-induced charge carriers between CoP and g-C3N4. Based on the
measurements, it is proposed that the efficient electron collecting effect of CoP
can be attributed to the superior interfacial contact and Schottky junction
between the CoP and g-C3N4 interfaces. Furthermore, the excellent electrical
conductivity and low overpotential of CoP make water reduction easier. This work
demonstrates that the construction of a 2D/2D structure based on a suitable Fermi
level is crucial for enhancing the Schottky effect of transition metal
phosphides.
PMID- 29942956
TI - Phosphinecarboxamide as an unexpected phosphorus precursor in the chemical vapour
deposition of zinc phosphide thin films.
AB - This paper demonstrates the use of phosphinecarboxamide as a facile phosphorus
precursor, which can be used alongside zinc acetate for the chemical vapour
deposition (CVD) of adherent and crystalline zinc phosphide films. Thin films of
Zn3P2 have a number of potential applications and phosphinecarboxamide is a safer
and more efficient precursor than the highly toxic, corrosive and flammable
phosphine used in previous CVD syntheses.
PMID- 29942958
TI - Coupling desalination and energy storage with redox flow electrodes.
AB - Both freshwater shortage and energy crisis are global issues. Herein, we present
a double-function system of faradaic desalination and a redox flow battery
consisting of VCl3|NaI redox flow electrodes and a feed stream. The system has a
nominal cell potential (E0 = +0.79 V). During the discharge process, the salt
ions in the feed are extracted by the redox reaction of the flow electrodes,
which is indicated by salt removal. Stable and reversible salt removal capacity
and electricity can be achieved up to 30 cycles. The energy consumption is as low
as 10.27 kJ mol-1 salt. The energy efficiency is as high as 50% in the current
aqueous redox flow battery. With energy recovery, the desalination energy
consumption decreases greatly to 5.38 kJ mol-1; this is the lowest reported value
to date. This "redox flow battery desalination generator" can be operated in a
voltage range of 0.3-1.1 V. Our research provides a novel method for obtaining
energy-saving desalination and redox flow batteries.
PMID- 29942959
TI - Hydroxide-ion-conductive gas barrier films based on layered double
hydroxide/polysulfone multilayers.
AB - A dual-functional organic-inorganic film with gas barrier and hydroxide ion
conductivity properties was fabricated via the layer-by-layer assembly of layered
double hydroxide (LDH) nanoplates and quaternary ammonium grafted polysulfone
(QAPSF). By incorporating inorganic flakes with high ionic conductivity and gas
barrier effects into an ion-conductive polymer matrix, this work overcomes the
commonly-believed incompatibility between gas blocking and ionic conduction.
PMID- 29942960
TI - Precursor-mediated synthesis of Cu2-xSe nanoparticles and their composites with
TiO2 for improved photocatalysis.
AB - The direct synthesis of copper selenide nanoparticles from the reaction of
ditertiarybutyl selenide tBu2Se with copper(ii) trifluoroacetate Cu(TFA)2 under
mild conditions is reported. The isolation of a molecular species during the
course of this reaction, established as [Cu2(TFA)2(tBu2Se)3], by spectroscopic
studies and single crystal X-ray structure analysis, confirmed that metal
selenide NPs are formed via this intermediate species containing a reduced copper
center. Extending this reaction in the presence of commercial TiO2 (P25) offered
an easy synthesis of copper selenide-titania nanocomposites with different Cu/Ti
ratios. These nanocomposites, well-characterized by powder XRD, STEM, TEM, BET,
XPS, EDX and UV-Vis studies, were examined as photocatalysts for the degradation
of formic acid (FA). The nCu2-xSe-TiO2 nanocomposites with low mol% of copper
selenide, i.e. n = 0.1 and 0.3 mol%, displayed a superior catalytic activity over
P25, which is an established benchmark for photocatalysis under UV light.
PMID- 29942963
TI - Revisiting graphene-polymer nanocomposite for enhancing anticorrosion
performance: a new insight into interface chemistry and diffusion model.
AB - Graphene is impermeable to all molecules and has high chemical stability, which
makes it an excellent anticorrosion coating for metals. However, current studies
have indicated that galvanic coupling between graphene and a metal actually
accelerates corrosion at the interface. Due to the insulating nature of polymers,
graphene-polymer composite coatings with a strong interaction between the filler
and the polymer matrix are an alternative means of addressing this issue.
Nevertheless, such coatings require well-dispersed graphene flakes to lengthen
the diffusion paths of gases or liquids, while preventing the formation of a
conducting network from graphene to the metal. The difficulty in preparing such
coatings was mainly due to problems with the control of the assembled phase
during interfacial reactions. Herein, the interactions between the filler and the
polymer were found to be a key factor governing anticorrosion performance, which
has scarcely been previously reported. The advantage of graphene as a filler in
anticorrosion coatings lies in its dispersibility and miscibility with both the
casting solvent and the polymer. Electrochemically exfoliated graphene (EC
graphene) with appropriate surface functionalities that allow high miscibility
with waterborne polyurethane (PU) and hydrophobic epoxy has been found to be an
ideal filler that outperforms other graphene materials such as graphene oxide
(GO) and reduced graphene oxide (rGO). Furthermore, a bilayer coating with EC
graphene additives for PU over epoxy has been found to reduce the corrosion rate
(CR) to 1.81 * 10-5 mm per year. With a graphene loading of less than 1%, this
represents the lowest CR ever achieved for copper and steel substrates and a
diffusion coefficient that is lower by a factor of nearly 2.2 than that of the
pristine polymer. Furthermore, we have shown that by controlling the amount of
graphene loaded in the polymer galvanic corrosion favored by the formation of an
interconnected graphene percolation network can successfully be limited. The
present study, together with a facile and eco-friendly method of nanocomposite
synthesis, may pave the way toward practical applications in the development of
graphene-based anticorrosion coatings.
PMID- 29942964
TI - Metal-free C(sp3)-H bond sulfonyloxylation of 2-alkylpyridines and alkylnitrones.
AB - Pyridin-2-ylmethyl tosylate derivatives are obtained in high yields from 2
alkylpyridine 1-oxides via a [3,3]-sigmatropic rearrangement of the adduct
between 2-alkylpridine 1-oxides with benzenesulfonyl chlorides. Moreover,
alkylnitrones also undergo [3,3]-sigmatropic rearrangement to give alpha
tosylated ketones after hydrolysis. Substitution reactions with nucleophiles then
lead to diverse useful functionalizations for the synthesis of pincer ligands.
PMID- 29942969
TI - Correction: In vitro selection of electrochemical peptide probes using
bioorthogonal tRNA for influenza virus detection.
AB - Correction for 'In vitro selection of electrochemical peptide probes using
bioorthogonal tRNA for influenza virus detection' by Tara Bahadur K. C. et al.,
Chem. Commun., 2018, 54, 5201-5204.
PMID- 29942970
TI - Surfactant-free synthesis of Cu2O yolk-shell cubes decorated with Pt
nanoparticles for enhanced H2O2 detection.
AB - Pt decorated yolk-shell Cu2O cubes are obtained using a surfactant-free and
multiple-step method. Porous yolk-shell cubic structures, together with
synergistic effects between Pt and Cu2O, endow the yolk-shell Pt-Cu2O based
nonenzymatic H2O2 sensors with enhanced sensing performance.
PMID- 29942971
TI - Bicycloaromaticity and Baird-type bicycloaromaticity of dithienothiophene-bridged
[34]octaphyrins.
AB - Aromatic properties of two recently synthesized dithienothiophene-bridged (DTT)
[34]octaphyrins have been investigated by calculating magnetically induced
current densities and vertical excitation energies. These intriguing molecules
have been proposed to be the first synthesized neutral bicycloaromatic compounds.
The triplet state of their dications was even suggested to be Baird-type
bicycloaromatic rendering them very interesting as a new prototype of molecules
possessing simultaneously the two rare types of aromaticity. Here, we investigate
computationally the aromatic properties of the neutral as well as the singly and
doubly charged DTT-bridged [34]octaphyrins. Our study provides unambiguous
information about changes in the aromatic properties of the DTT-bridged
[34]octaphyrins upon oxidation. The calculations identify two independent
diatropic ring currents in the neutral DTT-bridged [34]octaphyrins, showing that
they are indeed bicycloaromatic. The current-density flow of the two independent
ring currents of the bicycloaromatic compounds are visualized and individual
aromatic pathways are quantified by performing numerical integration. The
calculations show that two independent diatropic ring currents can indeed be
sustained by molecules consisting of two aromatic rings that share a common set
of pi electrons. The current density calculations on the singly charged DTT
bridged [34]octaphyrins show that they are weakly antiaromatic, which does not
agree with the suggested aromatic character deduced from spectroscopical studies.
The triplet state of the two DTT-bridged [34]octaphyrin cations with very similar
molecular structures have unexpectedly different aromatic character. One of them
is Baird-type bicycloaromatic, whereas the triplet state of the other dication
has one aromatic and one nonaromatic ring, which could not be resolved from
available spectroscopical data. Calculations of excitation energies reveal that a
simple model cannot be employed for interpreting the electronic excitation
spectra of the present molecules, because more than 20 excited states contribute
to the spectra above 2.5 eV (500 nm) showing the importance of computations. The
present work illustrates how detailed information about molecular aromaticity can
nowadays be obtained by scrutinizing calculated current densities.
PMID- 29942972
TI - The limited extent of the electronic modulation of chlorins and bacteriochlorins
through chromene-annulation.
AB - Optical data (UV-vis absorption and fluorescence emission spectra, including
fluorescence yields and lifetimes) and electrochemical measurements are used to
quantify the modulation of the electronic properties of meso
tetrakis(pentafluorophenyl)-chlorin diol and -bacteriochlorin tetraols upon
intramolecular chromene-annulation, including the investigation of regio- and
stereoisomers. The small modulations of the frontier orbitals of the
porphyrinoids are rationalized using DFT computations and can be traced to small
electronic effects due to the co-planarized meso-aryl groups in combination with
conformational effects.
PMID- 29942973
TI - Asymmetric total synthesis of (+)-ovafolinins A and B.
AB - (+)-Ovafolinins A and B are two homologous lignans containing unique polycyclic
skeletons. Benefiting from a highly diastereoselective alkylation of (S)
Taniguchi lactone, a double Friedel-Crafts reaction, a global debenzylation and a
Cu(OAc)2-enabled benzylic oxidative cyclization, we present herein an efficient
synthetic approach to (+)-ovafolinins A and B.
PMID- 29942974
TI - An innovative and efficient route to the synthesis of metal-based
glycoconjugates: proof-of-concept and potential applications.
AB - With a view to developing more efficient strategies to the functionalization of
metallodrugs with carbohydrates, we here report on an innovative and efficient
synthetic route to generate gold(iii) glycoconjugates in high yields and purity.
The method is based on the initial synthesis of the zinc(ii)-dithiocarbamato
intermediate [ZnII(SSC-Inp-GlcN)2] (Inp = isonipecotic moiety; GlcN = amino
glucose) followed by the transfer of the glucoseisonipecoticdithiocarbamato
ligand to the gold(iii) center via transmetallation reaction between the zinc(ii)
intermediate and K[AuIIIBr4] in 1 : 2 stoichiometric ratio, yielding the
corresponding glucose-functionalized gold(iii)-dithiocarbamato derivative
[AuIIIBr2(SSC-Inp-GlcN)]. No protection/deprotection of the amino-glucose
scaffold and no chromatographic purification were needed. The synthetic protocol
was optimized for glucose precursors bearing the amino function at either the C2
or the C6 position, and works in the case of both alpha and beta anomers. The
application of the synthetic strategy was also successfully extended to other
metal ions of biomedical interest, such as gold(i) and platinum(ii), to obtain
[AuI(SSC-Inp-GlcN)(PPh3)] and [PtII(SSC-Inp-GlcN)2], respectively. All compounds
were fully characterized by elemental analysis, mid- and far-IR, mono- and
multidimensional NMR spectroscopy, and, where possible, X-ray crystallography.
Results and potential applications are here discussed.
PMID- 29942975
TI - Interplay between hydrogen bonding and n->pi* interaction in an analgesic drug
salicin.
AB - The competition and cooperation between weak intermolecular interactions are
important in determining the conformational preferences of molecules.
Understanding the relative strengths of these effects in the context of potential
drug candidates is therefore essential. We use a combination of gas-phase
spectroscopy and quantum-chemical calculations to elucidate the nature of such
interactions for the analgesic salicin [2-(hydroxymethyl)phenyl beta-d
glucopyranoside], an analog of aspirin found in willow bark. Of several possible
conformers, only three are observed experimentally, and these are found to
correspond with the three lowest energy conformers obtained from density
functional theory calculations and simulated Franck-Condon spectra. Natural bond
orbital analyses show that these are characterized by a subtle interplay between
weak n->pi* interaction and conventional strong hydrogen bond, with additional
insights into this interaction provided by analysis of quantum theory of atoms in
molecules and symmetry-adapted perturbation theory calculations. In contrast, the
higher energy conformers, which are not observed experimentally, are mostly
stabilized by the hydrogen bond with negligible contribution of n->pi*
interaction. The n->pi* interaction results in a preference for the benzyl
alcohol group of salicin to adopt a gauche conformation, a characteristic also
found when salicin is bound to the beta-glucosidase enzyme. As such,
understanding the interplay between these weak interactions has significance in
the rationalization of protein structures.
PMID- 29942977
TI - Dilated cardiomyopathy with re-worsening left ventricular ejection fraction.
AB - Re-worsening left ventricular ejection fraction (LVEF) is observed in some
patients with dilated cardiomyopathy (DCM) despite initial improvements in LVEF.
We analyzed cardiac outcomes and clinical variables associated with this re
worsening LVEF. A total of 180 newly diagnosed DCM patients who received only
pharmacotherapy were enrolled. Echocardiography was performed after 6, 12, 24,
and 36 months after initiation of pharmacotherapy. Patients were divided into
three groups: (1) Improved: (n = 113, 63%), defined as those > 10% increase in
LVEF after 12 months and no decrease (> 10%) between 12 and 36 months; (2) Re
worse: (n = 12, 7%), those with > 10% increase in LVEF after 12 months but with
decrease (> 10%) between 12 and 36 months; and (3) Not-improved: (n = 55: 30%),
those with no increase in LVEF (> 10%) after 12 months. Patients with re-worse
group were older (P = 0.04) and had higher brain natriuretic peptide (BNP) levels
after 12 months (P = 0.002) than those in the Improved group. Major cardiac
events (sudden death, implantation of a ventricular assist device, and death due
to heart failure,) were observed in 13 (7%) patients after 36 months of
pharmacotherapy. Multivariate analysis revealed that the Re-worse group had a
higher risk for cardiac events (hazard ratio 11.7, 95% confidence interval 1.9
90.7, P = 0.01) than the Improved group, but had a similar risk compared with the
Not-improved group. Re-worsening LVEF was associated with poor cardiac outcomes
in newly diagnosed DCM patients. Age and persistently high-BNP levels after
improvement in LVEF were significantly associated with re-worsening LVEF.
PMID- 29942976
TI - Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer.
AB - : Papillary thyroid cancer is a prevalent endocrine malignancy. Although
alterations in glutamine metabolism have been reported in several types of
hematological and solid tumors, little is known about the functions of glutamine
and glutaminolysis-associated proteins in papillary thyroid cancer. Here, we
demonstrated the glutamine dependence of papillary thyroid cancer cells, and with
the use of RT2-PCR arrays, we screened for the aberrant overexpression of
glutaminase in human papillary thyroid cancer tissues and cells. These results
were later confirmed via real-time PCR, Western blots, and immunohistochemical
staining. We found that the levels of glutaminase were significantly correlated
with extrathyroidal extension. Inhibition of GLS suppressed glutaminolysis and
reduced mitochondrial respiration. The proliferative, viable, migratory, and
invasive abilities of papillary thyroid cancer cells were impaired by both the
pharmacological inhibition and the genetic knockdown of glutaminase.
Additionally, the inhibition of glutaminase deactivated the mechanistic target of
the rapamycin complex 1 (mTORC1) signaling pathway, promoting autophagy and
apoptosis. Collectively, these findings show that glutaminase-mediated glutamine
dependence may be a potential therapeutic target for papillary thyroid cancer.
KEY MESSAGES: PTC cells are glutamine-dependent, and GLS is aberrantly
overexpressed in PTC. Inhibition of GLS suppressed glutaminolysis and reduced
mitochondrial respiration. Inhibition of GLS impairs the viability of PTC cells.
GLS blockade causes deactivation of mTORC1 and induction of autophagy and
apoptosis. GLS may be a potential therapeutic target for PTC.
PMID- 29942978
TI - A multicenter trial of extracorporeal cardiac shock wave therapy for refractory
angina pectoris: report of the highly advanced medical treatment in Japan.
AB - We have previously demonstrated that cardiac shock wave therapy (CSWT)
effectively improves myocardial ischemia through coronary neovascularization both
in a porcine model of chronic myocardial ischemia and in patients with refractory
angina pectoris (AP). In this study, we further addressed the efficacy and safety
of CSWT in a single-arm multicenter study approved as a highly advanced medical
treatment by the Japanese Ministry of Health, Labour and Welfare. Fifty patients
with refractory AP [mean age 70.9 +/- 12.6 (SD) years, M/F 38/12] without the
indications of percutaneous coronary intervention (PCI) or coronary artery bypass
grafting (CABG) were enrolled in 4 institutes in Japan. Ischemic myocardial
regions in the left ventricle (LV) were identified by drug-induced stress
myocardial perfusion imaging (MPI). Shock waves (200 shots/spot at 0.09 mJ/mm2)
were applied to 40-60 spots in the ischemic myocardium 3 times in the first week.
The patients were followed up for 3 months thereafter. Forty-one patients
underwent CSWT and completed the follow-up at 3 months. CSWT markedly improved
weekly nitroglycerin use [from 3.5 (IQR 2 to 6) to 0 (IQR 0 to 1)] and the
symptoms [Canadian Cardiovascular Society functional class score, from 2 (IQR 2
to 3) to 1 (IQR 1 to 2)] (both P < 0.001). CSWT also significantly improved 6-min
walking distance (from 384 +/- 91 to 435 +/- 122 m, P < 0.05). There were no
significant changes in LV ejection fraction evaluated by echocardiography and LV
stroke volume evaluated by cardiac magnetic resonance imaging (from 56.3 +/- 14.7
to 58.8 +/- 12.8%, P = 0.10, and from 52.3 +/- 17.4 to 55.6 +/- 15.7 mL, P =
0.15, respectively). Percent myocardium ischemia assessed by drug-induced stress
MPI tended to be improved only in the treated segments (from 16.0 +/- 11.1 to
12.1 +/- 16.2%, P = 0.06), although no change was noted in the whole LV. No
procedural complications or adverse effects related to the CSWT were noted. These
results of the multicenter trial further indicate that CSWT is a useful and safe
non-invasive strategy for patients with refractory AP with no options of PCI or
CABG.
PMID- 29942979
TI - Age-moderating effect in prepotent response inhibition in boys with Asperger
syndrome: a 2.5 years longitudinal study.
AB - Following our previous cross-sectional analysis, indicating age-related
improvements of response inhibition in a random-motor-generation task (MPT) in
adolescents with Asperger syndrome (AS), the present study reports data from a
2.5-year follow-up examination in the original sample. We found more marked
improvements within the follow-up interval in younger AS children, while older AS
boys as well as typically developing (TD) boys remained at a relatively constant
level throughout. The current longitudinal study further substantiates the notion
that AS children (on average) catch up with TD children when they grow older as
regards the basic inhibition of developing routine response patterns.
PMID- 29942980
TI - Relationship between duration of untreated prodromal symptoms and symptomatic and
functional recovery.
AB - Our previous study has found that a long duration of untreated prodromal symptoms
(DUPrS) does not increase the conversion risk to psychosis in individuals with
attenuated psychosis syndrome (APS). However, whether a long DUPrS will lead to
other poor outcomes remains unknown. The purpose of this study was to analyse the
association between the DUPrS and outcomes (symptomatic and functional recovery)
in APS population. A post hoc analysis was performed in 391 individuals with APS
as identified by the structured interview. APS subjects had follow-up interviews
every 6 months for 2 years following diagnosis. Poor functional outcome was
defined as a Global Assessment of Functioning (GAF) score less than 60 at the
time of follow-up. Poor symptomatic outcome was defined as at least one of the
positive symptoms rated scores of 3 or higher. A post hoc analysis was performed
in 391 individuals with APS as identified by the structured interview. APS
subjects had follow-up interviews every 6 months for 2 years following diagnosis.
Poor functional outcome was defined as a Global Assessment of Functioning (GAF)
score less than 60 at the time of follow-up. Poor symptomatic outcome was defined
as at least one of the positive symptoms rated scores of 3 or higher. Of total
391 individuals, 334 were followed up for 2 years to assess clinical outcome, 82
(24.6%) had shown conversion to psychosis, 79 (23.7%) met the criteria of poor
functioning outcome, and 145 (43.4%) met the criteria of poor symptomatic
outcome. A significant correlation between GAF scores and DUPrS was observed in
the non-converter group, but not in the converters. Individuals with APS who had
a longer DUPrS were correlated with poorer functional outcome. However, it was
not correlated with poorer symptomatic outcome. While a longer DUPrS was not
related to poor symptomatic outcome, it was significantly related to poor
functional outcome. Our findings highlight the importance of reducing DUPrS to
decrease future functional impairment in populations at risk for psychosis.
PMID- 29942981
TI - Increasing the number of available ranks in virus taxonomy from five to ten and
adopting the Baltimore classes as taxa at the basal rank.
AB - This opinion article makes a case for increasing the number of ranks used in
virus taxonomy from the current five to ten (as are used to classify cellular
life forms) and placing the Baltimore classes in the proposed basal rank of
domain. These suggestions aim at initiating the process of accommodation of
Baltimore classes in virus taxonomy and extension of the virus taxonomy scale to
encompass also the most distant relationships.
PMID- 29942982
TI - Early morphological changes in tissues when replacing abdominal wall defects by
bacterial nanocellulose in experimental trials.
AB - Experimental trials were done on five dogs to explore if an anterior abdominal
wall defect could be repaired using wet (99.9%), compact BNC membranes produced
by the Medusomyces gisevii Sa-12 symbiotic culture. The abdominal wall defect was
simulated by middle-midline laparotomy, and a BNC membrane was then fixed to open
aponeurotic edges with blanket suture (Prolene 4-0, Ethicon). A comparative study
was also done to reinforce the aponeurotic defect with both the BNC membrane and
polypropylene mesh (PPM) (Ultrapro, Ethicon). The materials were harvested at 14
and 60 days postoperative to visually evaluate their location in the abdominal
tissues and evaluate the presence of BNC and PPM adhesions to the intestinal
loops, followed by histologic examination of the tissue response to these
prosthetics. The BNC exhibited good fixation to the anterior abdominal wall to
form on the 14th day a capsule of loose fibrin around the BNC. Active reparative
processes were observed at the BNC site at 60 days post-surgery to generate new,
stable connective-tissue elements (macrophages, giant cells, fibroblasts, fibrin)
and neocapillaries. Negligible intraperitoneal adhesions were detected between
the BNC and the intestinal loops as compared to the case of PPM. There were no
suppurative complications throughout the postsurgical period. We noticed on the
60th day after the BNC placement that collagenous elements and new capillary
vessels were actively formed in the abdominal wall tissues, generating a dense
postoperative cicatrix whose intraperitoneal adhesions to the intestinal loops
were insignificant compared to the PPM graft.
PMID- 29942983
TI - A Simple Approach for Comparing the In Vitro Dissolution Profiles of Highly
Variable Drug Products: a Proposal.
AB - When in vitro dissolution profile variability prohibits the use of the F2 metric,
there currently is no satisfactory alternative available. Published reports
evaluating alternative approaches such as Multivariate Statistical Distance and
use of a bootstrap F2 identify sources of bias that can limit the utility of
these alternatives. Within veterinary medicine, an additional complication is the
potential magnitude of interlot variability associated with dosage forms
containing "natural" ingredients. In situations when both interlot and intralot
variability need to be factored in the test and reference profile comparison, we
designed a method that integrates such concepts as F2, USP S1 and S2 criteria and
statistical tolerance limits. Unlike F2, this alternative approach integrates a
statistical confidence into the determination through the use of tolerance limits
about the reference product profile. Moreover, while differences in product
variability, along with differences in mean profiles, will influence the
comparability assessment, this method does not impose the need to confirm
homogeneity of variances: there is not direct statistical comparison of test
versus reference dissolution data. For more typical situations when interlot
variability is not a concern, the F2 component can be omitted from the profile
comparison. Lastly, by being a model-independent approach, we avoid the potential
for introducing error into the comparability determination due either to model
misspecification or problems associated with a lack of collinearity. This
manuscript details this alternative approach and the results of performance
characterization efforts to illustrate its behavior under a range of potential
situations.
PMID- 29942985
TI - Longitudinal Change in High-Cost Prosocial Behaviors of Defending and Including
during the Transition to Adulthood.
AB - Despite high profile examples that are highlighted in the popular media, we know
little about high-cost prosocial behaviors such as defending and including, and
how these behaviors might change over time and vary by individual. Thus, this
study explored defending and including behaviors across the transition to
adulthood by assessing growth and profiles of these high-cost prosocial behaviors
over a four-year time span. In addition the study explored gender, emotional
(sympathy), cognitive (personal values), individual (self-esteem), and relational
(maternal warmth) factors during adolescence that predicted profiles of defending
and including during the transition to adulthood. Participants were 469
individuals (52% female, 70% European American) who participated at four time
points (ages 18-21). Growth curve analyses showed that defending and including
behaviors decreased slightly across the transition to adulthood and these
behaviors tended to vary as a function of the target of the behavior. Latent
profile analyses revealed three groups at each age, one with low, one with
medium, and one with high levels of defending and including. The discussion
focused on the prevalence and change in defending and including behaviors during
the transition to adulthood, as well as the variability that exists in high-cost
behavioral profiles.
PMID- 29942986
TI - How to Attain a Popularity Goal? Examining the Mediation Effects of Popularity
Determinants and Behaviors.
AB - Popularity has been examined extensively in recent years, particularly regarding
its behavioral correlates. However, much less is known about the social cognitive
processes related to popularity and the strategies to attain popularity. This
study examined the longitudinal association between popularity goal and
popularity status by focusing on the mediation effects of perceived contributing
behaviors for popularity (i.e., popularity determinants) and actual behaviors in
a sample of 5th and 6th graders (N = 382; 47% girls) in China. The results
revealed that participants' popularity goal indirectly related to aggression,
academic performance, and prosocial behaviors through the mediation of the
corresponding popularity determinant perceptions. Furthermore, participants'
popularity goal longitudinally predicted their later popularity status changes
through the mediation of perceptions of prosocial behaviors as a popularity
determinant and prosocial behaviors. The findings of this study were discussed in
relationship to their cultural context.
PMID- 29942984
TI - Improving the standards for gut microbiome analysis of fecal samples: insights
from the field biology of Japanese macaques on Yakushima Island.
AB - Fecal DNA-based 16S ribosomal RNA (rRNA) gene sequencing using next-generation
sequencers allows us to understand the dynamic gut microbiome adaptation of
animals to their specific habitats. Conventional techniques of fecal microbiome
analysis have been developed within the broad contexts defined by human biology;
hence, many of these techniques are not immediately applicable to wild nonhuman
primates. In order to establish a standard experimental protocol for the analysis
of the gut microbiomes of wild animals, we selected the Japanese macaques (Macaca
fuscata yakui) on Yakushima Island. We tested different protocols for each stage
of fecal sample processing: storage, DNA extraction, and choice of the sequencing
region in the bacterial 16S rRNA gene. We also analyzed the gut microbiome of
captive Japanese macaques as the control. The comparison of samples obtained from
identical macaques but subjected to different protocols showed that the tested
storage methods (RNAlater and lysis buffer) produced effectively the same
composition of bacterial operational taxonomic units (OTUs) as the standard
frozen storage method, although the relative abundance of each OTU was
quantitatively affected. Taxonomic assignment of the detected bacterial groups
was also significantly affected by the region being sequenced, indicating that
sequencing regions and the corresponding polymerase chain reaction (PCR) primer
pairs for the 16S rRNA gene should be carefully selected. This study improves the
current standard methods for microbiome analysis in wild nonhuman primates.
Japanese macaques were shown to be a suitable model for understanding microbiome
adaptation to various environments.
PMID- 29942987
TI - Distress Intolerance Mediates the Relationship between Child Maltreatment and
Nonsuicidal Self-Injury among Chinese Adolescents: A Three-Wave Longitudinal
Study.
AB - Nonsuicidal self-injury (NSSI) is a serious public health concern among
adolescents. Identifying risk factors of NSSI is important to effectively prevent
or reduce such behavior. Child maltreatment is one of the most widely recognized
risk factors for NSSI. How child maltreatment and NSSI is related, however, is
still unclear. The present study tested the temporal relationship between
physical and emotional abuse and NSSI, with distress intolerance as the potential
mediator. Potential gender differences on these associations were also tested. We
assessed all study variables among 2259 Chinese adolescents (53.8% females; Mage
= 15.11 years, SD = 1.57) for three times at 6-month intervals. The results
showed that distress intolerance only mediated the relationship between emotional
abuse and NSSI, but not between physical abuse and NSSI. In addition, this
mediation effect of distress intolerance was significant only for females. The
findings of this study can help researchers and practitioners understand pathways
by which child maltreatment impacts adolescent NSSI. Implications for preventions
and interventions of NSSI were discussed.
PMID- 29942988
TI - Fluorescence Guidance in Surgical Oncology: Challenges, Opportunities, and
Translation.
AB - Surgical resection continues to function as the primary treatment option for most
solid tumors. However, the detection of cancerous tissue remains predominantly
subjective and reliant on the expertise of the surgeon. Surgery that is guided by
fluorescence imaging has shown clinical relevance as a new approach to detecting
the primary tumor, tumor margins, and metastatic lymph nodes. It is a technique
to reduce recurrence and increase the possibility of a curative resection. While
significant progress has been made in developing this emerging technology as a
tool to assist the surgeon, further improvements are still necessary. Refining
imaging agents and tumor targeting strategies to be a precise and reliable
surgical strategy is essential in order to translate this technology into patient
care settings. This review seeks to provide a comprehensive update on the most
recent progress of fluorescence-guided surgery and its translation into the
clinic. By highlighting the current status and recent developments of
fluorescence image-guided surgery in the field of surgical oncology, we aim to
offer insight into the challenges and opportunities that require further
investigation.
PMID- 29942989
TI - Influence of Multidrug Resistance-Associated Proteins on the Excretion of the
ABCC1 Imaging Probe 6-Bromo-7-[11C]Methylpurine in Mice.
AB - PURPOSE: Multidrug resistance-associated proteins (MRPs) mediate the
hepatobiliary and renal excretion of many drugs and drug conjugates. The positron
emission tomography (PET) tracer 6-bromo-7-[11C]methylpurine is rapidly converted
in tissues by glutathione-S-transferases into its glutathione conjugate, and has
been used to measure the activity of Abcc1 in the brain and the lungs of mice.
Aim of this work was to investigate if the activity of MRPs in excretory organs
can be measured with 6-bromo-7-[11C]methylpurine. PROCEDURES: We performed PET
scans with 6-bromo-7-[11C]methylpurine in groups of wild-type, Abcc4(-/-) and
Abcc1(-/-) mice, with and without pre-treatment with the prototypical MRP
inhibitor MK571. RESULTS: 6-Bromo-7-[11C]methylpurine-derived radioactivity
predominantly underwent renal excretion. In blood, MK571 treatment led to a
significant increase in the AUC and a decrease in the elimination rate constant
of radioactivity (kelimination,blood). In the kidneys, there were significant
decreases in the rate constant for radioactivity uptake from the blood
(kuptake,kidney), kelimination,kidney, and the rate constant for tubular
secretion of radioactivity (kurine). Experiments in Abcc4(-/-) mice indicated
that Abcc4 contributed to renal excretion of 6-bromo-7-[11C]methylpurine-derived
radioactivity. CONCLUSIONS: Our data suggest that 6-bromo-7-[11C]methylpurine may
be useful to assess the activity of MRPs in the kidneys as well as in other
organs (brain, lungs), although further work is needed to identify the MRP
subtypes involved in the disposition of 6-bromo-7-[11C]methylpurine-derived
radioactivity.
PMID- 29942991
TI - Baicalin attenuates collagen-induced arthritis via inhibition of JAK2-STAT3
signaling and regulation of Th17 cells in mice.
AB - This study focused on the potential therapeutic effect of Baicalin on collagen
induced arthritis (CIA) in mice and the underlying mechanisms. Baicalin (200
mg/kg) was administrated after the induction of CIA for 42 days. Therapeutic
effects were evaluated by arthritic scores, X-rays and assessment of
histopathological joint destruction. The production of TNF-alpha,IL-6,IL-17,IL
1beta were also measured. The percentage of Th17 cells in splenocytes were
determined by flow cytometry analysis. Our results showed that Baicalin treatment
attenuated the severity of arthritis of CIA mice and reduced the levels of
several cytokines. Further mechanistic investigations revealed that Baicalin
suppressed the expression and phosphorylation of JAK2 and STAT3 protein in
splenocytes tissue. Moreover, the percentage of Th17 cells in splenocytes also
downregulated by Baicalin. Our experiment indicate that CIA mice can be
alleviated by Baicalin treatment via inhibition of JAK2-STAT3 signaling and
regulation of Th17 cells in mice.
PMID- 29942992
TI - ?
PMID- 29942990
TI - In Vivo Evaluation of Magnetic Targeting in Mice Colon Tumors with Ultra-Magnetic
Liposomes Monitored by MRI.
AB - PURPOSE: The development of theranostic nanocarriers as an innovative therapy
against cancer has been improved by targeting properties in order to optimize the
drug delivery to safely achieve its desired therapeutic effect. The aim of this
paper is to evaluate the magnetic targeting (MT) efficiency of ultra-magnetic
liposomes (UML) into CT26 murine colon tumor by magnetic resonance imaging (MRI).
PROCEDURES: Dynamic susceptibility contrast MRI was applied to assess the
bloodstream circulation time. A novel semi-quantitative method called %I0.25,
based on the intensity distribution in T2*-weighted MRI images was developed to
compare the accumulation of T2 contrast agent in tumors with or without MT. To
evaluate the efficiency of magnetic targeting, the percentage of pixels under the
intensity value I0.25 (I0.25 = 0.25(Imax - Imin)) was calculated on the intensity
distribution histogram. RESULTS: This innovative method of processing MRI images
showed the MT efficiency by a %I0.25 that was significantly higher in tumors
using MT compared to passive accumulation, from 15.3 to 28.6 %. This methodology
was validated by ex vivo methods with an iron concentration that is 3-fold higher
in tumors using MT. CONCLUSIONS: We have developed a method that allows a semi
quantitative evaluation of targeting efficiency in tumors, which could be applied
to different T2 contrast agents.
PMID- 29942993
TI - ?
PMID- 29942994
TI - ?
PMID- 29942995
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PMID- 29942996
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PMID- 29942998
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PMID- 29942997
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PMID- 29942999
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PMID- 29943001
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PMID- 29943000
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PMID- 29943002
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PMID- 29943003
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PMID- 29943004
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PMID- 29943005
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PMID- 29943006
TI - [New endoscopic methods: hemostasis by over-the-scope clip (OTSC) and endoscopic
full-thickness resection with the Full Thickness Resection Device (FTRD)].
PMID- 29943007
TI - [Undescended testis: current pathways of diagnostics and treatment].
PMID- 29943008
TI - [Drowning - Near-Drowning].
PMID- 29943009
TI - [Valgus instability of the elbow in throwing athletes].
PMID- 29943010
TI - [Shoulder pain in athletes - 5 steps from diagnosis to successful treatment].
PMID- 29943011
TI - [Articular cartilage lesions in athletes].
PMID- 29943013
TI - ?
PMID- 29943012
TI - [Rupture of the proximal hamstring tendon].
PMID- 29943014
TI - ?
PMID- 29943015
TI - ?
PMID- 29943016
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PMID- 29943017
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PMID- 29943018
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PMID- 29943020
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PMID- 29943019
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PMID- 29943021
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PMID- 29943022
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PMID- 29943023
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PMID- 29943024
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PMID- 29943025
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PMID- 29943027
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PMID- 29943026
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PMID- 29943028
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PMID- 29943029
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PMID- 29943030
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PMID- 29943031
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PMID- 29943032
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PMID- 29943034
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PMID- 29943035
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PMID- 29943033
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PMID- 29943037
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PMID- 29943036
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PMID- 29943038
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PMID- 29943039
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PMID- 29943042
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PMID- 29943041
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PMID- 29943040
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PMID- 29943043
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PMID- 29943044
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PMID- 29943046
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PMID- 29943048
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PMID- 29943047
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PMID- 29943049
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PMID- 29943050
TI - [Platelets - what should a GP know about].
PMID- 29943053
TI - A novel very simple laparoscopic hepatic inflow occlusion apparatus for
laparoscopic liver surgery.
AB - BACKGROUND: Control of bleeding is extremely important for laparoscopic liver
resection. We introduce a new and operationally simple laparoscopic hepatic
inflow occlusion apparatus (LHIOA) and its successful application in laparoscopic
surgery for patients with cirrhosis. METHODS: The self-designed LHIOA was
constructed using a tracheal catheter (7.5#) and infusion set. The tracheal
catheter and infusion set were trimmed to 30 and 70 cm, to serve as an occlusion
tube and occlusion tape, respectively. After establishment of pneumoperitoneum,
the occlusion tape was inserted to encircle the hepatoduodenal ligament. The
occlusion tube was then introduced and the ends of the occlusion tape were pulled
out of it to occlude the hepatic inflow. Under intermittent vascular occlusion
with the LHIOA, the liver parenchyma was transected using an ultrasonic scalpel
and monopolar electrocoagulation. Outcomes of the application of the LHIOA in
hepatocellular carcinoma patients with cirrhosis (LHIOA group, n = 46) were
compared with patients undergoing laparoscopic hepatectomy without LHIOA (non
LHIOA group, n = 46), using one-to-one propensity case-matched analysis. RESULTS:
The LHIOA effectively occluded the hepatic inflow while showing no damage to the
hepatoduodenal ligament. The time required for presetting the LHIOA is 6.8 +/-
0.6 min. The conversion rate in the non-LHIOA group was 13.0% while there was no
conversion in the occlusion group (P < 0.001). The median blood loss of patients
in the LHIOA group (60 ml, range 50-200 ml) was significantly less than that of
patients in the non-LHIOA group (250 ml, range 100-800) (P < 0.001). Transfusion
was required in 8 patients in the non-LHIOA group while no transfusion was
required in the LHIOA group. The median operative time in the LHIOA group (157
min, range 80-217 min) was significantly shorter than that in the non-LHIOA group
(204 min, range 105-278 min) (P < 0.001). CONCLUSIONS: The new LHIOA is
effective, safe, and simple. It can significantly reduce conversion rate, blood
loss, and operative time. It facilitates laparoscopic liver resection and is
recommended for use.
PMID- 29943052
TI - beta-N-Acetylglucosaminidase MthNAG from Myceliophthora thermophila C1, a
thermostable enzyme for production of N-acetylglucosamine from chitin.
AB - Thermostable enzymes are a promising alternative for chemical catalysts currently
used for the production of N-acetylglucosamine (GlcNAc) from chitin. In this
study, a novel thermostable beta-N-acetylglucosaminidase MthNAG was cloned and
purified from the thermophilic fungus Myceliophthora thermophila C1. MthNAG is a
protein with a molecular weight of 71 kDa as determined with MALDI-TOF-MS. MthNAG
has the highest activity at 50 degrees C and pH 4.5. The enzyme shows high
thermostability above the optimum temperature: at 55 degrees C (144 h, 75%
activity), 60 degrees C (48 h, 85% activity; half-life 82 h), and 70 degrees C
(24 h, 33% activity; half-life 18 h). MthNAG releases GlcNAc from chitin
oligosaccharides (GlcNAc)2-5, p-nitrophenol derivatives of chitin
oligosaccharides (GlcNAc)1-3-pNP, and the polymeric substrates swollen chitin and
soluble chitosan. The highest activity was detected towards (GlcNAc)2. MthNAG
released GlcNAc from the non-reducing end of the substrate. We found that MthNAG
and Chitinase Chi1 from M. thermophila C1 synergistically degraded swollen chitin
and released GlcNAc in concentration of approximately 130 times higher than when
only MthNAG was used. Therefore, chitinase Chi1 and MthNAG have great potential
in the industrial production of GlcNAc.
PMID- 29943054
TI - Local infiltration versus laparoscopic-guided transverse abdominis plane block in
laparoscopic cholecystectomy: double-blinded randomized control trial.
AB - BACKGROUND: Transverse abdominal plane block (TAP) is a new technique of regional
block described to reduce postoperative pain in laparoscopic cholecystectomy
(LC). Recent reports describe an easy technique to deliver local anesthetic agent
under laparoscopic guidance. METHODS: This randomized control trial was designed
to compare the effectiveness of additional laparoscopic-guided TAP block against
the standard full thickness port site infiltration. 45 patients were randomized
in to each arm after excluding emergency LC, conversions, ones with coagulopathy,
pregnancy and allergy to local anesthetics. All cases were four ports LC.
Interventions-Both groups received standard port site infiltration with 3-5 ml of
0.25% bupivacaine. The test group received additional laparoscopic-guided TAP
block with 20 ml of 0.25% bupivacaine subcostally, between the anterior axillary
and mid clavicular lines. As outcome measures the pain score, opioid requirement,
episodes of nausea and vomiting and time to mobilize was measured at 6 hourly
intervals. RESULTS: The two groups were comparable in the age, gender, body mass
index, indication for cholecystectomy difficulty index and surgery duration. The
pain score at 6 h (P = 0.043) and opioid requirement at 6 h (P = 0.026) was
higher in the TAP group. These were similar in subsequent assessments. Other
secondary outcomes were similar in the two groups. CONCLUSION: Laparoscopic
guided transverses abdominis plane block using plain bupivacaine does not give an
additional pain relief or other favorable outcomes. It can worsen the pain
scores. Pre registration: The trial was registered in Sri Lanka clinical trial
registry-SLCTR/2016/011 ( http://www.slctr.lk/trials/357 ).
PMID- 29943055
TI - Application of ultrasonography to high-tie and low-tie vascular ligation of the
inferior mesenteric artery in laparoscopic colorectal cancer surgery: technical
notes.
AB - BACKGROUND: Two ligation techniques can be applied in laparoscopy for left-sided
colorectal cancer: (1) high-tie (HT), transection at the level of the inferior
mesenteric artery (IMA); and (2) low-tie (LT), transection below the IMA, at the
level of superior rectal artery (SRA), preserving the left colic artery (LCA).
However, even with preoperative images, it can still be a challenge to identify
these structures due to intraoperative individual conditions. In this study, we
assess the use intraoperative ultrasonography (IOUS) to aid us in identifying the
IMA and its branches to the SRA, LCA, and sigmoid artery. METHODS: We performed
IOUS in 18 patients diagnosed with left-sided colorectal cancer. Preoperatively,
a three-dimensional computed tomography (3D-CT) angiography was obtained in
majority of the patients, to visualize the IMA and its branches. Two patients
were contraindicated to receive a contrast study, hence, was unable to undergo 3D
CT angiography. The resected specimen was grossly examined for the study. The
bifurcation types were identified and compared using different modalities:
preoperative 3D-CT, IOUS, and gross examination of the resected specimen.
RESULTS: The branching of the IMA revealed by IOUS was consistent to the findings
preoperatively by the 3D-CT and postoperatively by the resected specimen. The
IOUS result of the two patients without preoperative 3D-CT evaluation was also
consistent with the post-operative bifurcation type. CONCLUSIONS: IOUS is an easy
and feasible modality which aids in detecting the branching of the IMA during LT
and HT ligation in laparoscopic left-sided colorectal surgery. It can serve as an
adjunct modality for 3D-CT angiography and can also be considered a safe
alternative option for cases wherein 3D-CT angiography is unavailable.
PMID- 29943056
TI - Transcystic versus traditional laparoscopic common bile duct exploration: its
advantages and a meta-analysis.
AB - BACKGROUND: The best approach for treating common bile duct stones remains a
matter of debate. Traditional laparoscopic common bile duct exploration (LCBDE)
can cause adverse events such as stenosis of the bile duct. Moreover, with
advances in technology and surgical skills, the use of laparoscopic transcystic
common bile duct exploration (LTCBDE) is gradually rising. OBJECTIVES: To compare
the safety, feasibility, and short-term clinical benefits of LTCBDE and LCBDE
through matched cases. METHODS: Web of science, Cochrane, PubMed, and CNKI were
searched systematically to identify studies published between January 2007 and
December 2017 that compared LTCBDE and LCBDE without a restriction of languages.
This meta-analysis was performed using Review Manager 5.3. RESULTS: Twenty-one
studies matched the selection criteria, including 1561 cases of LTCBDE and 1500
cases of LCBDE. There was no obvious difference in stone clearance (OR 1.44, 95%
CI 0.84-2.47; P = 0.18). However, LTCBDE had a shorter operative time (MD -
17.72, 95% CI - 19.42 to - 16.02; P < 0.00001) and shorter hospital stay (MD -
2.20, 95% CI - 2.32 to - 2.08; P < 0.00001). Besides, the LTCBDE group showed
significantly better results for blood loss (MD - 7.61, 95% CI - 8.85 to - 6.37;
P < 0.00001) and postoperative complications (OR 0.28, 95% CI 0.19-0.41; P <
0.00001). In addition, LTCBDE was more cost efficient (MD - 2.51, 95% CI - 2.72
to - 2.30; P < 0.00001). Further, we calculated the absolute mean of operative
time (LTCBDE:LCBDE = 97.56:117.81 min), hospital stay (LTCBDE:LCBDE = 5.22:8.91
days), hospital expenses (LTCBDE:LCBDE = 8646.121:11848.31 RMB), blood loss
(LTCBDE:LCBDE = 29.3:52.0 ml), the rate of CBD stone clearance (LTCBDE:LCBDE =
92.8:95.0%), and postoperative complications (LTCBDE:LCBDE = 6.7:14.6%) in both
groups to obtain more convincing results. CONCLUSIONS: The stone clearance of
LTCBDE was equal to that of LCBDE, and LTCBDE demonstrated a shorter operative
time, lower blood loss, and other advantages. Thus, the surgical procedure of
laparoscopic transcystic choledochotomy is feasible and safe.
PMID- 29943058
TI - Long-term follow-up after sleeve gastrectomy versus Roux-en-Y gastric bypass
versus one-anastomosis gastric bypass: a prospective randomized comparative study
of weight loss and remission of comorbidities.
AB - BACKGROUND: One-Anastomosis Gastric Bypass (OAGB) has exponentially increased in
the last decade, as it is associated with very low complications, mortality,
readmissions and reoperations rates, and shows excellent short- and long-term
benefits of weight loss and resolution of comorbidities. The aim of this study
was to compare the effect of SG, RYGB, and OAGB, on short- and long-term weight
loss and comorbidities resolution. METHODS: A prospective randomized clinical
study of all morbidly obese patients undergoing SG, RYGB, and OAGB, as primary
bariatric procedures, was performed. Patients were randomly assigned into 3
groups: those patients undergoing SG, those ones undergoing RYGB and those ones
undergoing OAGB. BMI, excess BMI loss (EBMIL) and remission of type 2 diabetes
(T2DM), hypertension (HT), and dyslipidemia (DL) were assessed. RESULTS: 600
patients were included in the study, 200 in each group. Follow-up rate at 5 years
postoperatively was 91% in SG group, 92% in RYGB, and 90% in OAGB. OAGB achieves
significantly greater EBMIL than RYGB and SG at 1, 2, and 5 years (p < 0.001,
respectively). At 5 years, OAGB achieves significantly greater remission of T2DM
(p = 0.027), HT (p = 0.006), and DL (p < 0.001) than RYGB and SG. RYGB did not
show significant superiority than SG in short- and long-term remission of T2DM
and HT, but achieves greater remission of DL (p < 0.001). CONCLUSION: OAGB
achieves superior mid- and long-term weight loss than RYGB and SG. There are no
significant differences in weight loss between SG and RYGB at 1, 2, and 5 years.
OAGB achieves better short- and long-term resolution rates of DM, HT, and DL than
SG and RYGB. RYGB and SG obtain similar T2DM and HT remissions, but RYGB reaches
significantly greater rates of DL remission. ClinicalTrials.gov Identifier:
NCT03467646.
PMID- 29943057
TI - Safety of single-incision robotic cholecystectomy for benign gallbladder disease:
a systematic review.
AB - BACKGROUND: Multiport laparoscopic cholecystectomy (MLC) is the gold standard
technique for cholecystectomy. In order to reduce postoperative pain and improve
cosmetic results, the application of the single-incision laparoscopic
cholecystectomy (SILC) technique was introduced, leading surgeons to face
important challenges. Robotic technology has been proposed to overcome some of
these limitations. The purpose of this review is to assess the safety of single
incision robotic cholecystectomy (SIRC) for benign disease. METHODS: An Embase
and Pubmed literature search was performed in February 2017. Randomized
controlled trial and prospective observational studies were selected and assessed
using PRISMA recommendations. Primary outcome was overall postoperative
complication rate. Secondary outcomes were postoperative bile leak rate, total
conversion rate, operative time, wound complication rate, postoperative hospital
stay, and port site hernia rate. The outcomes were analyzed in Forest plots based
on fixed and random effects model. Heterogeneity was assessed using the I2
statistic. RESULTS: A total of 13 studies provided data about 1010 patients who
underwent to SIRC for benign disease of gallbladder. Overall postoperative
complications rate was 11.6% but only 4/1010 (0.4%) patients required further
surgery. A postoperative bile leak was reported in 3/950 patients (0.3%).
Conversion occurred in 4.2% of patients. Mean operative time was 86.7 min
including an average of 42 min should be added as for robotic console time. Wound
complications occurred in 3.7% of patients. Median postoperative hospital stay
was 1 day. Port site hernia at the latest follow-up available was reported in
5.2% of patients. CONCLUSIONS: The use of the Da Vinci robot in single-port
cholecystectomy seems to have similar results in terms of incidence and grade of
complications compared to standard laparoscopy. In addition, it seems affected by
the same limitations of single-port surgery, consisting of an increased operative
time and incidence of port site hernia.
PMID- 29943059
TI - National trends of endoscopic retrograde cholangiopancreatography utilization and
outcomes in decompensated cirrhosis.
AB - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) can be
challenging in patients with decompensated cirrhosis (DC) due to increased risk
of adverse events related to liver dysfunction. Limited data exist regarding its
national utilization in patients with DC. We aim to determine the trends in
utilization and outcomes of ERCP among patients with DC in US hospitalizations.
METHODS: We identified hospitalizations undergoing ERCP (diagnostic and
therapeutic) between 2000 and 2013 from the National Inpatient Sample (NIS)
database and used validated ICD9-CM codes to identify DC hospitalizations. We
utilized Cochrane-Armitage test to identify changes in trends and multivariable
survey regression modeling for adjusted odds ratios (aOR) for adverse outcomes
and mortality predictors. RESULTS: There were 43782 cases of ERCPs performed in
DC patients during the study period. Absolute number of ERCPs performed in this
population from 2000 to 2013 showed an upward trend; however, the proportion of
DC patients undergoing ERCP remained stable. We noted significant decrease in
utilization of diagnostic ERCP and an increase of therapeutic ERCPs (P < 0.01).
There was a significant decrease in the mean length of stay for DC patients
undergoing ERCP from 8.2 days in 2000 to 7.2 days in 2013 (P < 0.01) with an
increase in the mean cost of hospitalization from $17053 to $19825 (P < 0.001).
Mortality rates showed a downward trend from 2000 to 2013 from 13.6 to 9.6% (P <
0.01). Increasing age, Hispanic race, diagnosis of hypertension and diabetes
mellitus, and private insurance were related to adverse discharges(P < 0.01).
Increasing age, presence of hepatic encephalopathy, and sepsis were associated
with higher mortality (P < 0.01). CONCLUSIONS: There is an increasing trend in
therapeutic ERCP utilization in DC hospitalizations nationally. There is an
overall decrease in mortality in DC hospitalizations undergoing ERCP. This
improvement in mortality suggests improvement in both procedural technique and
peri-procedural care as well as overall decreasing mortality in cirrhosis.
PMID- 29943060
TI - Impact of 3D printing technology on the comprehension of surgical liver anatomy.
AB - BACKGROUND AND AIMS: Surgical planning in liver resection depends on the precise
understanding of the three-dimensional (3D) relation of tumors to the
intrahepatic vascular trees. This study aimed to investigate the impact of 3D
printing (3DP) technology on the understanding of surgical liver anatomy.
METHODS: We selected four hepatic tumors that were previously resected. For each
tumor, a virtual 3D reconstruction (VIR) model was created from multi-detector
computed tomography (MDCT) and was prototyped using a 3D printer. Forty-five
surgical residents were evenly assigned to each group (3DP, VIR, and MDCT
groups). After evaluation of the MDCT scans, VIR model, or 3DP model of each
tumor, surgical residents were asked to assign hepatic tumor locations and state
surgical resection proposals. The time used to specify the tumor location was
recorded. The correct responses and time spent were compared between the three
groups. RESULTS: The assignment of tumor location improved steadily from MDCT, to
VIR, and to 3DP, with a mean score of 34.50, 55.25, and 80.92, respectively.
These scores were out of 100 points. The 3DP group had significantly higher
scores compared with other groups (p < 0.001). Furthermore, 3DP significantly
improved the accuracy of surgical resection proposal (p < 0.001). The mean
accuracy of the surgical resection proposal for 3DP, VIR, and MDCT was 57, 25,
and 25%, respectively. The 3DP group took significantly less time, compared with
other groups (p < 0.005). The mean time spent on assessing the tumor location for
3DP, VIR, and MDCT groups was 93, 223, and 286 s, respectively. CONCLUSIONS: 3D
printing improves the understanding of surgical liver anatomy for surgical
residents. The improved comprehension of liver anatomy may facilitate laparoscopy
or open liver resection.
PMID- 29943061
TI - A propensity score-matched analysis of robotic versus open pancreatoduodenectomy
for pancreatic cancer based on margin status.
AB - BACKGROUND: No study has shown the oncologic non-inferiority of robotic
pancreatoduodenectomy (RPD) versus open pancreatoduodenectomy (OPD) for
pancreatic cancer (PC). METHODS: This is a single institution propensity score
matched study comparing RPD and ODP for resectable PC, based on factors
predictive of R1 resection (<= 1 mm). Only patients operated on after completion
of the learning curve in both procedures and for whom circumferential margins
were assessed according to the Leeds pathology protocol were included. The
primary study endpoint was the rate of R1 resection. Secondary study endpoints
were as follows: number of examined lymph nodes (N), rate of perioperative
transfusions, percentage of patients receiving adjuvant therapies, occurrence of
local recurrence, overall survival, disease-free survival, and sample size
calculation for randomized controlled trials (RCT). RESULTS: Factors associated
with R1 resection were tumor diameter, number of positive N, N ratio, logarithm
odds of positive N, and duodenal infiltration. The matching process identified 20
RPDs and 24 OPDs. All RPDs were completed robotically. R1 resection was
identified in 11 RPDs (55.0%) and in 10 OPDs (41.7%) (p = 0.38). There was no
difference in the rate of R1 at each margin as well as in the proportion of
patients with multiple R1 margins. RPD and OPD were also equivalent with respect
to all secondary study endpoints, with a trend towards lower rate of blood
transfusions in RPD. Based on the figures presented herein, a non-inferiority RCT
comparing RPD and OPD having the rate of R1 resection as the primary study
endpoint requires 3355 pairs. CONCLUSIONS: RPD and OPD achieved the same rate of
R1 resections in resectable PC. RPD was also non-inferior to OPD with respect to
all secondary study endpoints. Because of the high number of patients required to
run a RCT, further assessment of RPD for PC would require the implementation of
an international registry.
PMID- 29943062
TI - Nodal upstaging evaluation in NSCLC patients treated by robotic lobectomy.
AB - BACKGROUND: Open pulmonary resection is considered the gold standard treatment of
early-stage non-small cell lung cancer (NSCLC). However, in the last decades, the
use of minimal-invasive techniques has given promising results. Survival in lung
cancer, after surgery, depends on the number of pathological nodes (pN), thus
lymph nodal upstaging can be considered a surrogate for surgical quality of the
procedure. Several studies have demonstrated a lower rate of upstaging in video
assisted thoracic surgery than in open surgery, suggesting an approach-related
difference in lymphadenectomy. Features of robotic technique could consent a
lymph nodal dissection similar to open surgery. The aim of the study is to
compare nodal upstaging between thoracotomy and robotic approaches to evaluate
the oncologic radicality. METHODS: Between January 2013 and December 2016, 212
consecutive cN0 NSCLC patients underwent lobectomy and lymphadenectomy (N1 + N2
stations) by either thoracotomy (Open Group) or robotic surgery (Robotic Group).
RESULTS: Lobectomy and lymphadenectomy were performed in 106 cN0-cN1 NSCLC
patients by robotic surgery and in 106 cN0-cN1 NSCLC patients by open surgery. A
mean of 14.42 +/- 6.99 lymph nodes was removed in the Robotic Group (RG) and a
mean of 14.32 +/- 7.34 nodes in the Open Group (OG). Nodal upstaging was observed
in 22 (20.75%) RG patients and in 19 OG (17.92%) patients. CONCLUSIONS: Robotic
lobectomy for clinical N0-N1 NSCLC appears to be equivalent to thoracotomy in
terms of efficacy of lymph node dissection and nodal upstaging. Given that the
nodal upstaging is a surrogate of quality of surgery, we can consider robotic
lobectomy an appropriate procedure which ensures similar result to the open
approach.
PMID- 29943063
TI - A retrospective multicenter analysis on redo-laparoscopic anti-reflux surgery:
conservative or conversion fundoplication?
AB - BACKGROUND: Nearly 20% of patients who undergo hiatal hernia (HH) repair and anti
reflux surgery (ARS) report recurrent HH at long-term follow-up and may be
candidates for redo surgery. Current literature on redo-ARS has limitations due
to small sample sizes or single center experiences. This type of redo surgery is
challenging due to rare but severe complications. Furthermore, the optimal
technique for redo-ARS remains debatable. The purpose of the current multicenter
study was to review the outcomes of redo-fundoplication and to identify the best
ARS repair technique for recurrent HH and gastroesophageal reflux disease (GERD).
METHODS: Data on 975 consecutive patients undergoing hiatal hernia and GERD
repair were retrospectively collected in five European high-volume centers.
Patient data included demographics, BMI, techniques of the first and redo
surgeries (mesh/type of ARS), perioperative morbidity, perioperative
complications, duration of hospitalization, time to recurrence, and follow-up. We
analyzed the independent risk factors associated with recurrent symptoms and
complications during the last ARS. Statistical analysis was performed using
GraphPad Prism(r) and R software(r). RESULTS: Seventy-three (7.49%) patients
underwent redo-ARS during the last decade; 71 (98%) of the surgeries were
performed using a minimally invasive approach. Forty-two (57.5%) had conversion
from Nissen to Toupet. In 17 (23.3%) patients, the initial Nissen fundoplication
was conserved. The initial Toupet fundoplication was conserved in 9 (12.3%)
patients, and 5 (6.9%) had conversion of Toupet to Nissen. Out of the 73
patients, 10 (13%) underwent more than one redo-ARS. At 8.5 (1-107) months of
follow-up, patients who underwent reoperation with Toupet ARS were less
symptomatic during the postoperative period compared to those who underwent
Nissen fundoplication (p = 0.005, OR 0.038). Patients undergoing mesh repair
during the redo-fundoplication (21%) were less symptomatic during the
postoperative period (p = 0.020, OR 0.010). The overall rate of complications
(Clavien-Dindo classification) after redo surgery was 11%. Multivariate analysis
showed that the open approach (p = 0.036, OR 1.721), drain placement (p = 0.0388,
OR 9.308), recurrence of dysphagia (p = 0.049, OR 8.411), and patient age (p =
0.0619, OR 1.111) were independent risk factors for complications during the last
ARS. CONCLUSIONS: Failure of ARS rarely occurs in the hands of experienced
surgeons. Redo-ARS is feasible using a minimally invasive approach. According to
our study, in terms of recurrence of symptoms, Toupet fundoplication is a
superior ARS technique compared to Nissen for redo-fundoplication. Therefore,
Toupet fundoplication should be considered in redo interventions for patients who
initially underwent ARS with Nissen fundoplication. Furthermore, mesh repair in
reoperations has a positive impact on reducing the recurrence of symptoms
postoperatively.
PMID- 29943064
TI - Minor laparoscopic liver resection as day-case surgery (without overnight
hospitalisation): a pilot study.
AB - BACKGROUND: Day-case surgery (DCS) has become increasingly popular over recent
years, as has laparoscopic liver resection (LLR) for the treatment of benign or
malignant liver tumours. The purpose of this prospective study was to demonstrate
the feasibility of minor LLR as DCS. METHODS: Prospective, intention-to-treat,
non-randomised study of patients undergoing minor LLR between July 2015 and
December 2017. Exclusion criteria were resection by laparotomy, major LLR,
difficult locations for minor LLR, history of major abdominal surgery,
hepatobiliary procedures without liver parenchyma resection, cirrhosis with Child
> A and/or portal hypertension, significant medical history and exclusion
criteria for DCS. The primary endpoint was the unplanned overnight admission
rate. Secondary endpoints were the reason for exclusion, complication data,
criteria for DCS evaluation, satisfaction and compliance with the protocol.
RESULTS: One hundred sixty-seven patients underwent liver resection during the
study period. LLR was performed in 92 patients (55%), as DCS in 23 patients
(25%). Reasons for minor LLR were liver metastasis (n = 9), hepatic adenoma (n =
5), hepatocellular carcinoma (n = 4), ciliated hepatic foregut cyst (n = 2) and
other benign tumours (n = 3). All day-case minor LLR, except two patients,
consisted of single wedge resection, while one patient underwent left lateral
sectionectomy. There were four unplanned overnight admissions (17.4%), one
unscheduled consultation (4.3%), two hospital readmissions (8.6%) and no major
complications/mortality. Compliance with the protocol was 69.5%. Satisfaction
rate was 91%. CONCLUSION: In selected patients, day-case minor LLR is feasible
with acceptable complication and readmission rates. Day-case minor LLR can
therefore be legitimately proposed in selected patients.
PMID- 29943065
TI - Role of indo-cyanine green (ICG) fluorescence in laparoscopic adrenalectomy: a
retrospective review of 55 Cases.
AB - BACKGROUND: Indo-Cyanine Green Fluorescence is an emerging technology with more
frequent use in laparoscopic and robotic surgery. It relies on near-infrared
(NIR) fluorescence to demonstrate tissue perfusion with demarcation of tissue
planes and vascular pedicles. The aim of the study is to evaluate the role of
this technology in laparoscopic adrenalectomy (LA). METHODS: 55 patients
underwent laparoscopic adrenalectomy using NIR Fluorescence enabled laparoscope.
All cases received a standard initial dose of 5-mg dye to aid tissue
visualization. Surgery proceeded with "fluorescence mode" demonstrating real-time
NIR images superimposed on standard white-light imaging. The timing, number of
doses were dictated by the operating surgeon, which were recorded and correlated
with intra-operative fluorescence visualization. RESULTS: 54 patients underwent
successful LA, with one conversion in a case of large pheochromocytoma due to
difficult hemostasis. The lag between ICG administration and visualization of
adrenal fluorescence varied between 30 and 75 s. The total duration of adrenal
parenchymal fluorescence after a single dose did not exceed 15 min in our series.
Average total administered dose was 14.4 mg. We suffered no mortality. There were
no adverse effects due to the dye. 5 patients suffered Grade I complications,
with one patient suffering Grade II and IV complication each, as per Clavien
Dindo Classification. Final histopathology demonstrated pheochromocytoma,
adrenocortical adenoma, adrenocortical carcinoma, cushing's adenoma,
aldosteronoma, and myelolipoma. CONCLUSION: We describe our initial positive
experience with ICG fluorescence in LA, with a detailed description of dye
administration in our study. The technology offers real-time differentiation of
tissues and identification of vascular structures, providing immediate guidance
during surgery. Further evaluation of its role in adrenocortical malignancy is
warranted. NIR fluorescence is a safe, useful addition in laparoscopic
adrenalectomy which will undergo further refinement over time.
PMID- 29943066
TI - Long-term outcomes of laparoscopy-assisted distal gastrectomy versus open distal
gastrectomy for gastric cancer: a 10-year single-institution experience.
AB - BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer has
been widely applied; however, its oncologic efficacy has yet been well
established. The study aimed to compare the long-term oncologic outcomes of LADG
versus open distal gastrectomy (ODG) on gastric cancer. METHODS: The
clinicopathologic data of gastric cancer patients who underwent distal
gastrectomy with curative intent from October 2004 through September 2014 were
included and analyzed in a retrospective cohort. The last follow-up was September
2016. RESULTS: 769 eligible patients (LADG 414 vs. ODG 355) were included in the
study. No significant difference was observed between the groups in 5-year DFS
(LADG 61.2% vs. ODG 59.1%; p = 0.384) and OS rates (LADG 65.8% vs. ODG 66.3%; p =
0.750). During surgery, though LADG group had longer operating time, the blood
loss was less than ODG group. LADG group had faster postoperative recovery course
including shorter time to oral intake, ambulation, and discharge time.
Postoperative complication rate within 30 days showed no significant difference
between the groups (LADG 15.7% vs. ODG 13.0%; p = 0.281). Age over 65 years old,
blood loss > 200 ml, postoperative complication, and advanced T and N stage were
identified as independent risk factors for DFS and OS. CONCLUSIONS: LADG could
yield similar oncologic outcomes compared with ODG in treating distal gastric
cancer. However, the findings need to be further confirmed through ongoing
prospective randomized controlled trials.
PMID- 29943067
TI - What are the reasons for a longer operation time in robotic gastrectomy than in
laparoscopic gastrectomy for stomach cancer?
AB - BACKGROUND: Many studies have shown that robotic gastrectomy requires a longer
operation time than laparoscopic gastrectomy. However, no study has analyzed the
exact reason for this difference in detail. We therefore investigated the reasons
why more time is needed in robotic gastrectomy. METHODS: Ten consecutive cases of
robotic distal gastrectomy (RDG) performed in our institution were selected to
measure the operation time in detail. Ten cases of laparoscopic distal
gastrectomy (LDG) performed during the same period were chosen for comparison.
The operation videos and electronic medical records of these 20 patients were
retrospectively reviewed. The overall operation time, operation time in each
step, and time required for instrument changes were measured. The number of
intraoperative instrument changes and camera cleanings were also counted.
RESULTS: The overall operation time (including effective time and junk time) was
56.8 min longer for RDG than LDG (273.7 vs. 216.9 min, respectively; p = 0.000).
The effective time was only 15.3 min longer for RDG than LDG (145.9 vs. 130.6
min, respectively; p = 0.094). The time needed for the six technical steps was
also not significantly different between the two groups. However, the junk time
(instrument setup and docking or positioning of surgical arms) was 41.5 min
longer for RDG than LDG (127.8 vs. 86.2 min, respectively; p = 0.001). The number
of instrument changes was not different between RDG and LDG (p = 0.277), but the
time required for each was longer for RDG than LDG (p = 0.000). The number of
camera cleanings was lower for RDG than LDG (10.7 vs. 15.5 times, respectively; p
= 0.005). CONCLUSIONS: To reduce the operation time in RDG, a smarter and simpler
system for setup should be developed to reduce the junk time. Additionally, a
system for swifter instrument changes and more sophisticated energy devices are
warranted to reduce the effective time.
PMID- 29943068
TI - Long-term results of laparoscopic versus open intraperitoneal onlay mesh
incisional hernia repair: a propensity score-matched analysis.
AB - BACKGROUND: Intraperitoneal onlay mesh repair (IPOM) of incisional hernia is
performed by laparoscopic and open access. The aim of the present study is to
compare open versus laparoscopic surgery specifically using an IPOM technique for
incisional hernia repair. METHODS: A propensity score-matched observational
single center study of patients that underwent IPOM between 2004 and 2015 was
conducted. The primary outcome was hernia recurrence; secondary outcomes include
length of stay, surgical site infections (SSI), complications, and localization
of recurrence. RESULTS: Among 553 patients with incisional hernia repair, 59%
underwent laparoscopic and 41% open IPOM. A total of 184 patients completed
follow-up. After a mean follow-up of 5.5 years recurrence rate was 20% in
laparoscopic and 19% in open repair (p = 1.000). Patients undergoing laparoscopic
IPOM had significantly reduced operation time (median 120 vs. 180 min, p <
0.001), shorter hospital stays (6 vs. 8 days, p = 0.002), less complications (10
vs. 23%, p = 0.046), and fewer SSI (1 vs. 21%, p < 0.001). CONCLUSIONS:
Laparoscopic IPOM is associated with reduced morbidity compared to open IPOM for
incisional hernia repair.
PMID- 29943069
TI - Estimating urban above ground biomass with multi-scale LiDAR.
AB - BACKGROUND: Urban trees have long been valued for providing ecosystem services
(mitigation of the "heat island" effect, suppression of air pollution, etc.);
more recently the potential of urban forests to store significant above ground
biomass (AGB) has also be recognised. However, urban areas pose particular
challenges when assessing AGB due to plasticity of tree form, high species
diversity as well as heterogeneous and complex land cover. Remote sensing, in
particular light detection and ranging (LiDAR), provide a unique opportunity to
assess urban AGB by directly measuring tree structure. In this study, terrestrial
LiDAR measurements were used to derive new allometry for the London Borough of
Camden, that incorporates the wide range of tree structures typical of an urban
setting. Using a wall-to-wall airborne LiDAR dataset, individual trees were then
identified across the Borough with a new individual tree detection (ITD) method.
The new allometry was subsequently applied to the identified trees, generating a
Borough-wide estimate of AGB. RESULTS: Camden has an estimated median AGB density
of 51.6 Mg ha-1 where maximum AGB density is found in pockets of woodland;
terrestrial LiDAR-derived AGB estimates suggest these areas are comparable to
temperate and tropical forest. Multiple linear regression of terrestrial LiDAR
derived maximum height and projected crown area explained 93% of variance in tree
volume, highlighting the utility of these metrics to characterise diverse tree
structure. Locally derived allometry provided accurate estimates of tree volume
whereas a Borough-wide allometry tended to overestimate AGB in woodland areas.
The new ITD method successfully identified individual trees; however, AGB was
underestimated by <= 25% when compared to terrestrial LiDAR, owing to the
inability of ITD to resolve crown overlap. A Monte Carlo uncertainty analysis
identified assigning wood density values as the largest source of uncertainty
when estimating AGB. CONCLUSION: Over the coming century global populations are
predicted to become increasingly urbanised, leading to an unprecedented expansion
of urban land cover. Urban areas will become more important as carbon sinks and
effective tools to assess carbon densities in these areas are therefore required.
Using multi-scale LiDAR presents an opportunity to achieve this, providing a
spatially explicit map of urban forest structure and AGB.
PMID- 29943070
TI - Dendritic cell trafficking in tumor-bearing mice.
AB - Prostate cancer is one of the leading causes of cancer deaths, with no curative
treatments once it spreads. Alternative therapies, including immunotherapy, have
shown limited efficacy. Dendritic cells (DC) have been widely used in the
treatment of various malignancies. DC capture antigens and move to the lymphoid
organs where they prime naive T cells. Interaction between DC and T cells are
most active in lymph nodes and suppression of DC trafficking to lymph nodes
impairs the immune response. In this work, we aimed to study trafficking of DC in
vivo via various routes of delivery, to optimize the effectiveness of DC-based
therapy. A DC labeling system was developed using 1,1'-dioctadecyltetramethyl
indotricarbocyanine Iodine for in vivo fluorescent imaging. DC harvested from
C57B/6 mice were matured, labeled, and injected intravenously, subcutaneously, or
intratumorally, with or without antigen loading with whole tumor lysate, into
C57B/6 mice inoculated with RM-1 murine prostate tumor cells. Signal intensity
was measured in vivo and ex vivo. Signal intensity at the tumor site increased
over time, suggesting trafficking of DC to the tumor with all modes of injection.
Subcutaneous injection showed preferential trafficking to lymph nodes and tumor.
Intravenous injection showed trafficking to lungs, intestines, and spleen.
Subcutaneous injection of DC pulsed with whole tumor lysate resulted in the
highest increase in signal intensity at the tumor site and lymph nodes,
suggesting subcutaneous injection of primed DC leads to highest preferential
trafficking of DC to the immunocompetent organs.
PMID- 29943071
TI - Expression of CD3, PD-L1 and CTLA-4 in mammary and extra-mammary Paget disease.
AB - BACKGROUND: Mammary and extra-mammary Paget disease is a rare form of intra
epithelial glandular neoplasm which is characteristically recurrent and
necessitates multiple excisions that have an important impact on morbidity. Local
immuno-modulating treatments have been applied with promising results, but the
local immune markers of Paget disease have not been studied. AIM OF THE STUDY: To
investigate the local immune micro-environment of Paget disease. MATERIALS AND
METHODS: Sixty-four specimens from 41 patients, including cases with multiple
recurrences and underlying primary neoplasm, have been studied for their
expression of CD3, PD-L1 and CTLA-4. RESULTS: Nineteen cases were mammary; 22
were extra-mammary and involved the vulva, the anus, the inguinal region and the
lower extremity. PD-L1 was not expressed by any neoplastic lesion or the
associated lymphocytes. CTLA-4 expression was found in nine cases. Higher stromal
CD3 expression and moderate levels of intra-epithelial CD3 expression were
present in most cases. Biopsies, subsequent excision specimens and recurrences
showed the same immunohistochemical profile of CD3 and PD-L1, although there were
different levels of CTLA-4 in a few cases. The underlying lesions in mammary
Paget disease showed the same immunohistochemical profile as the intra-epithelial
neoplastic cells. The expression of the markers did not correlate with age, sex,
localization or recurrence. CONCLUSION: Paget disease is characterized by an
intense lymphocytic response, devoid of the immune-suppressive impact of the PD
L1 pathway, but with occasional CTLA-4 expression.
PMID- 29943072
TI - Novel microsurgical management of uveitis-glaucoma-hyphema syndrome.
AB - PURPOSE: To report a series of cases and microsurgical management of rarely
occurring uveitis-glaucoma-hyphema (UGH) syndrome in patients with single-piece
acrylic intraocular lens (IOL) placed in the capsular bag. METHODS: It was a
series of patients with UGH syndrome induced by posterior chamber IOL/capsular
bag complex instability (pseudophakodonesis), who underwent IOL fixation to the
iris. Visual acuity, intraocular pressure, number of glaucoma medications and IOL
status (position) were recorded by the same protocol before and 6 months after
the surgical treatment. RESULTS: The case series presents three patients with UGH
syndrome caused by single-piece acrylic IOL placed in-the-bag. Each patient had
uneventful phacoemulsification with posterior chamber IOL implantation few years
ago and pseudophakodonesis caused by weakened zonules from pseudoexfoliation with
subsequent development of UGH syndrome. IOL fixation to the iris with
satisfactory postoperative results was performed due to the development of UGH.
Signs of syndrome did not recur 6 months after the operation. CONCLUSION: UGH
syndrome can be induced by unstable in-the-bag IOL due to zonular laxity.
Depending on the severity of the syndrome, this condition can be fought by
applying a minimally invasive approach-IOL suturing to the iris with direct
observation under the surgical microscope precisely in the anticipated location
with no or minimal pupil deformation. Symptoms of UGH did not recur due to
increased stability of the IOL and, as a result of this, declined irritation of
the uveal tissue.
PMID- 29943073
TI - Seasonal incidence of ruptured abdominal aortic aneurysm and the influence of
atmospheric pressure: a systematic review and meta-analysis.
AB - Ruptured abdominal aortic aneurysm (rAAA) is a life-threatening condition with a
high mortality rate. Seasonal variations in the incidence of rAAA and the
influence of atmospheric pressure have been studied throughout decades; however,
the conclusions are contradictory. Therefore, we aimed to conduct a meta-analysis
and systematic review of literature on seasonal variations in rAAA incidence and
the influence of atmospheric pressure. Studies investigating seasonal variations
in rAAA incidence and influence of atmospheric pressure were retrieved. For
dichotomous data, we generated risk ratios (RRs) and 95% confidence intervals
(CIs) for rAAA incidence compared among seasons. The studies were subdivided
according to latitude, elevation, and climatic types, for subgroup comparisons.
Studies reporting monthly incidence and seasonal mortality were further
investigated. For continuous data, standardized mean differences (SMDs) and 95%
CIs were generated for atmospheric pressure comparisons. Twenty-four eligible
studies were included, comprising a total of 38,506 patients with rAAA. Pooled
rAAA incidence was 25% in spring, 23% in summer, 26% in autumn, and 26% in
winter. Pooled analysis demonstrated a statistically significant higher rAAA
incidence in winter than in summer (RR 1.10, P = 0.04) and in autumn than in
summer (RR 1.11, P < 0.00001). However, there was no statistically significant
difference among other seasons. In the study of the influence of atmospheric
pressure, no statistically significant difference was observed. In conclusion,
our study revealed a higher incidence of rAAA in autumn and winter than in
summer; however, atmospheric pressure was found to exert no influence.
PMID- 29943074
TI - ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively
collected ADMET database.
AB - Current pharmaceutical research and development (R&D) is a high-risk investment
which is usually faced with some unexpected even disastrous failures in different
stages of drug discovery. One main reason for R&D failures is the efficacy and
safety deficiencies which are related largely to absorption, distribution,
metabolism and excretion (ADME) properties and various toxicities (T). Therefore,
rapid ADMET evaluation is urgently needed to minimize failures in the drug
discovery process. Here, we developed a web-based platform called ADMETlab for
systematic ADMET evaluation of chemicals based on a comprehensively collected
ADMET database consisting of 288,967 entries. Four function modules in the
platform enable users to conveniently perform six types of drug-likeness analysis
(five rules and one prediction model), 31 ADMET endpoints prediction (basic
property: 3, absorption: 6, distribution: 3, metabolism: 10, elimination: 2,
toxicity: 7), systematic evaluation and database/similarity searching. We believe
that this web platform will hopefully facilitate the drug discovery process by
enabling early drug-likeness evaluation, rapid ADMET virtual screening or
filtering and prioritization of chemical structures. The ADMETlab web platform is
designed based on the Django framework in Python, and is freely accessible at
http://admet.scbdd.com/ .
PMID- 29943075
TI - Perceived Relationship Development in Anxious and Non-Anxious Adolescents: a
Person-Centered Five-Wave Longitudinal Study.
AB - Developmental changes in adolescents' relationships with parents and friends
intertwine, but individual differences in these relationships are likely to
emerge as not all adolescents develop similarly. Generalized anxiety symptoms may
underlie these individual differences, as these symptoms have frequently been
associated with interpersonal difficulties. This study examines relationship
quality development with parents and friends in adolescents with low and high
levels of generalized anxiety symptoms. A latent transition analysis was
performed in a two-cohort five-wave study design covering ages 12 to 16 (n = 923,
50.8% males) and 16 to 20 (n = 390, 43.4% males). About one-third of adolescents
with high levels of generalized anxiety symptoms perceived a turbulent
relationship with both their parents and best friends, whereas only one-tenth of
those with low levels of generalized anxiety symptoms did. Low levels as opposed
to high levels of generalized anxiety symptoms predicted a twice as high
likelihood to perceive harmonious relationships with both their parents and best
friends. Nevertheless, adolescents with low and high levels of generalized
anxiety symptoms exhibited similar trends in relationship development. Overall,
our findings indicate that generalized anxiety symptoms are not deterministic
markers for relationship difficulties as there were plenty of adolescents with
high levels of generalized anxiety symptoms that experienced no relationship
difficulties across adolescence.
PMID- 29943077
TI - Epidemiological changes in potential heart donors after brain death: a
retrospective 15 year cohort study.
AB - Changes in the causes of brain death may influence the numbers of hearts that can
be procured and transplanted. We retrospectively investigated whether the
distribution of causes responsible for brain death have changed over a 15-year
period in a cohort of 1286 potential heart donor (aged <= 60), and whether it
influenced heart procurement. Between 2001 and 2016, the age of potential donors
significantly increased (p < 0.0001) as well as the relative proportion of
postanoxic brain death, while that of traumatic brain injury decreased (p =
0.0007). A significant increase in the use of norepinephrine was detectable. The
number of transplanted hearts did not significantly change, with no differences
in the age of donors or in the causes of brain death. According to our data, in
our 15-year study period, significant changes in the causes of brain death
occurred (indicated by a reduction in potential donors following traumatic brain
injury) together with an increase in donor age. Nevertheless, the number of
transplanted hearts did not change probably thanks to a modified donor management
(as inferred by a different use of vasoactive drugs).
PMID- 29943076
TI - Pivotal role of LBD16 in root and root-like organ initiation.
AB - In the post-embryonic stage of Arabidopsis thaliana, roots can be initiated from
the vascular region of the existing roots or non-root organs; they are designated
as lateral roots (LRs) and adventitious roots (ARs), respectively. Some root-like
organs can also be initiated from the vasculature. In tissue culture, auxin
induced callus, which is a group of pluripotent root-primordium-like cells, is
formed via the rooting pathway. The formation of feeding structures from the
vasculature induced by root-knot nematodes also borrows the rooting pathway. In
this review, we summarize and discuss recent progress on the role of LATERAL
ORGAN BOUNDARIES DOMAIN16 (LBD16; also known as ASYMMETRIC LEAVES2-LIKE18,
ASL18), a member of the LBD/ASL gene family encoding plant-specific transcription
factors, in roots and root-like organ initiation. Different root and root-like
organ initiation processes have distinct priming mechanisms to specify founder
cells. All these priming mechanisms converge to activate LBD16 expression in the
primed founder cells. The activation of LBD16 expression leads to organ
initiation via promotion of cell division and establishment of root-primordium
identity. Therefore, LBD16 might play a common and pivotal role in root and root
like organ initiation.
PMID- 29943078
TI - [Psychosocial burden and strains in geriatric nursing: comparison of nursing
personnel with and without migration background].
AB - BACKGROUND: Because of demographic changes the nursing care sector is faced with
a lack of qualified employees in the medium and long term. The shortage in the
work force is caused by high workloads and unfavorable working conditions. In
response to this shortage, there have been attempts to recruit qualified nursing
staff from abroad and also to improve the integration of people with a migration
background living in Germany into the job market. METHODOLOGY: Based on a
quantitative cross-sectional study of 366 nurses, the psychosocial burden and
strains among employees with a migration background (n = 112) and without a
migration background (n = 254) were examined. For this purpose, 13 scales of the
German version of the Copenhagen Psychosocial Questionnaire (COPSOQ) were used
for the assessment of psychosocial factors at work. The results were compared
with professional group-specific reference values (geriatric care) from the
COPSOQ database. RESULTS: The comparison of nursing staff with and without a
migration background revealed that the emotional demands, work-privacy conflict
and role conflicts factors received a significantly better rating among nursing
staff with a migration background, while development opportunities were rated
worse by this population group. The surveyed nursing staff exhibited higher
stress values compared to the COPSOQ reference group in almost all scales.
CONCLUSION: Nursing staff with a migration background need to be supported with
respect to development opportunities. Suitable education and training measures
may offer adequate career perspectives and may encourage employees to stay in
their jobs.
PMID- 29943079
TI - [Critical discussion on the current quality debate on long-term care-a plea for a
systemic and empirical insight into the development and measurement of quality in
long-term care].
AB - Against the background of the quality debates on long-term care and recurrent
reform measures in politics on this topic, a critical discussion on the current
state of quality development, testing and reporting in Germany is presented. In
Germany, the linear model of Donabedian's structural, process and outcome quality
is still used as a basis for quality issues in nursing care; however,
international research suggests that multiple and mutually interacting factors
influence nursing quality and that a more systematic and systemic perspective for
the further development of nursing quality (especially of features, criteria and
indicators of nursing quality) appears more appropriate. This article intends to
open the perspective of the development, measurement and reporting of quality in
nursing and to make a critical contribution for a systemic theory development as
a relevant basis for future developments of quality evaluation programs and
quality reporting systems in long-term care.
PMID- 29943080
TI - Epitope Ligand Binding Sites of Blood Group Oligosaccharides in Lectins Revealed
by Pressure-Assisted Proteolytic Excision Affinity Mass Spectrometry.
AB - Affinity mass spectrometry using selective proteolytic excision and extraction
combined with MALDI and ESI mass spectrometry has been applied to the
identification of epitope binding sites of lactose, GalNac, and blood group
oligosaccharides in two blood group-specific lectins, human galectin-3 and
glycine max lectin. The epitope peptides identified comprise all essential amino
acids involved in carbohydrate recognition, in complete agreement with available
X-ray structures. Tryptic and chymotryptic digestion of lectins for proteolytic
extraction/excision-MS was substantially improved by pressure-enhanced digestion
using an automated Barocycler procedure (40 kpsi). Both previously established
immobilization on affinity microcolumns using divinyl sulfone and coupling of a
specific peptide glycoprobe to the gold surface of a biosensor chip were
successfully employed for proteolytic excision and extraction of carbohydrate
epitopes and affinity measurements. The identified epitope peptides could be
differentiated according to the carbohydrate employed, thus demonstrating the
specificity of the mass spectrometric approach. The specificities of the epitope
ligands for individual carbohydrates were further ascertained by affinity studies
using synthetic peptide ligands with immobilized carbohydrates. Binding
affinities of the synthetic ligand peptides to lactose, in comparison to the
intact full-length lectins, were determined by surface acoustic wave (SAW)
biosensor analysis and provided micromolar KD values for the intact lectins, in
agreement with results of previous ITC and SPR studies. Binding affinities of the
epitope peptides were approximately two orders of magnitude lower, consistent
with their smaller size and assembled arrangement in the carbohydrate recognition
domains. Graphical Abstract ?.
PMID- 29943081
TI - Variation in FPOP Measurements Is Primarily Caused by Poor Peptide Signal
Intensity.
AB - Fast photochemical oxidation of proteins (FPOP) may be used to characterize
changes in protein structure by measuring differences in the apparent rate of
peptide oxidation by hydroxyl radicals. The variability between replicates is
high for some peptides and limits the statistical power of the technique, even
using modern methods controlling variability in radical dose and quenching.
Currently, the root cause of this variability has not been systematically
explored, and it is unknown if the major source(s) of variability are structural
heterogeneity in samples, remaining irreproducibility in FPOP oxidation, or
errors in LC-MS quantification of oxidation. In this work, we demonstrate that
coefficient of variation of FPOP measurements varies widely at low peptide signal
intensity, but stabilizes to ~ 0.13 at higher peptide signal intensity. We
dramatically reduced FPOP variability by increasing the total sample loaded onto
the LC column, indicating that the major source of variability in FPOP
measurements is the difficulties in quantifying oxidation at low peptide signal
intensities. This simple method greatly increases the sensitivity of FPOP
structural comparisons, an important step in applying the technique to study
subtle conformational changes and protein-ligand interactions. Graphical Abstract
?.
PMID- 29943082
TI - The effect of experience and of dots' density and duration on the detection of
coherent motion in dogs.
AB - Knowledge about the mechanisms underlying canine vision is far from being
exhaustive, especially that concerning post-retinal elaboration. One aspect that
has received little attention is motion perception, and in spite of the common
belief that dogs are extremely apt at detecting moving stimuli, there is no
scientific support for such an assumption. In fact, we recently showed that dogs
have higher thresholds than humans for coherent motion detection (Kanizsar et al.
in Sci Rep UK 7:11259, 2017). This term refers to the ability of the visual
system to perceive several units moving in the same direction, as one coherently
moving global unit. Coherent motion perception is commonly investigated using
random dot displays, containing variable proportions of coherently moving dots.
Here, we investigated the relative contribution of local and global integration
mechanisms for coherent motion perception, and changes in detection thresholds as
a result of repeated exposure to the experimental stimuli. Dogs who had been
involved in the previous study were given a conditioned discrimination task, in
which we systematically manipulated dot density and duration and, eventually, re
assessed our subjects' threshold after extensive exposure to the stimuli.
Decreasing dot duration impacted on dogs' accuracy in detecting coherent motion
only at very low duration values, revealing the efficacy of local integration
mechanisms. Density impacted on dogs' accuracy in a linear fashion, indicating
less efficient global integration. There was limited evidence of improvement in
the re-assessment but, with an average threshold at re-assessment of 29%, dogs'
ability to detect coherent motion remains much poorer than that of humans.
PMID- 29943084
TI - Localization of Human Glutamate Dehydrogenases Provides Insights into Their
Metabolic Role and Their Involvement in Disease Processes.
AB - Glutamate dehydrogenase (GDH) catalyzes the reversible deamination of L-glutamate
to alpha-ketoglutarate and ammonia. In mammals, GDH contributes to important
processes such as amino acid and carbohydrate metabolism, energy production,
ammonia management, neurotransmitter recycling and insulin secretion. In humans,
two isoforms of GDH are found, namely hGDH1 and hGDH2, with the former being
ubiquitously expressed and the latter found mainly in brain, testis and kidney.
These two iso-enzymes display highly divergent allosteric properties, especially
concerning their basal activity, ADP activation and GTP inhibition. On the other
hand, both enzymes are thought to predominantly localize in the mitochondrial
matrix, even though alternative localizations have been proposed. To further
study the subcellular localization of the two human iso-enzymes, we created
HEK293 cell lines stably over-expressing hGDH1 and hGDH2. In these cell lines,
immunofluorescence and enzymatic analyses verified the overexpression of both
hGDH1 and hGDH2 iso-enzymes, whereas subcellular fractionation followed by
immunoblotting showed their predominantly mitochondrial localization. Given that
previous studies have only indirectly compared the subcellular localization of
the two iso-enzymes, we co-expressed them tagged with different fluorescent dyes
(green and red fluorescent protein for hGDH1 and hGDH2, respectively) and found
them to co-localize. Despite the wealth of information related to the functional
properties of hGDH1 and hGDH2 and the availability of the hGDH1 structure, there
is still an ongoing debate concerning their metabolic role and their involvement
in disease processes. Data on the localization of hGDHs, as the ones presented
here, could contribute to better understanding of the function of these important
human enzymes.
PMID- 29943083
TI - Resveratrol Boosts Cognitive Function by Targeting SIRT1.
AB - Cognitive decline is among the most devastating age-related conditions and is
rapidly becoming an important cause of disease burdens worldwide. New strategies
for the prevention and management of cognitive decline are needed. Resveratrol, a
polyphenolic compound, has been found to enhance brain health through multiple
signaling pathways. Optimal SIRT1 activation is the most crucial step in the
neuroprotection provided by resveratrol against cognitive impairment. This review
discusses several recent developments in our understanding of the mechanisms by
which resveratrol delay age-related cognitive decline through SIRT1. The
regulatory mechanisms include anti-oxidative, anti-inflammatory, anti-apoptotic
processes and autophagy regulation, as well as increases in cerebral blood flow
and improvements in the plasticity of synaptic pathways. Resveratrol, as well as
novel SIRT1 activators, is likely to provide promising therapeutic strategies for
impeding cognitive decline, repairing brain functions, and supporting healthy
aging.
PMID- 29943085
TI - Inhalation of Simulated Smog Atmospheres Affects Cardiac Function in Mice.
AB - The health effects of individual criteria air pollutants have been well
investigated. However, little is known about the health effects of air pollutant
mixtures that more realistically represent environmental exposures. The present
study was designed to evaluate the cardiac effects of inhaled simulated smog
atmospheres (SA) generated from the photochemistry of either gasoline and
isoprene (SA-G) or isoprene (SA-Is) in mice. Four-month-old female mice were
exposed for 4 h to filtered air (FA), SA-G, or SA-Is. Immediately and 20 h after
exposure, cardiac responses were assessed with a Langendorff preparation using a
protocol consisting of 20 min of global ischemia followed by 2 h of reperfusion.
Cardiac function was measured by index of left-ventricular developed pressure
(LVDP) and cardiac contractility (dP/dt) before ischemia. Pre-ischemic LVDP was
lower in mice immediately after SA-Is exposure (52.2 +/- 5.7 cm H2O compared to
83.9 +/- 7.4 cm H2O after FA exposure; p = 0.008) and 20 h after SA-G exposure
(54.0 +/- 12.7 cm H2O compared to 79.3 +/- 7.4 cm H2O after FA exposure; p =
0.047). Pre-ischemic left ventricular contraction dP/dtmax was lower in mice
immediately after SA-Is exposure (2025 +/- 169 cm H2O/sec compared to 3044 +/-
219 cm H2O/sec after FA exposure; p < 0.05) and 20 h after SA-G exposure (1864 +/
328 cm H2O/sec compared to 2650 +/- 258 cm H2O/sec after FA exposure; p = 0.05).
In addition, SA-G reduced the coronary artery flow rate 20 h after exposure
compared to the FA control. This study demonstrates that acute SA-G and SA-Is
exposures decrease LVDP and cardiac contractility in mice, indicating that
photochemically-altered atmospheres affect the cardiovascular system.
PMID- 29943086
TI - Transthoracic echocardiography and mortality in sepsis: are we there yet?
PMID- 29943087
TI - Beyond bleeps and alarms: live music by the bedside in the ICU.
PMID- 29943088
TI - The End of Phase 3 Clinical Trials in Biosimilars Development?
AB - Most patients still have limited or no access to life-changing therapeutic
proteins in the treatment of their cancer or autoimmune disorders. The current
clinical development model of biosimilars is expensive, and in most cases, large,
phase 3 trials do not provide meaningful information on the clinical equivalence
of biosimilars and reference compounds. At the same time, the development of
state-of-the-art orthogonal analytical methods has enabled a better understanding
of the structure and structure-function relationship of biotherapeutics. Hence,
we suggest here that a solid chemistry, manufacturing, and controls (CMC) package
and meaningful phase 1 studies will leave limited uncertainty on biosimilarity,
which can be addressed-if needed-by post-approval, long-term follow-up studies
(post-approval studies, pharmacovigilance, real world evidence data and
registries, and possibly new post-approval models to be developed). We believe
that this new approach may be more appropriate than 600- to 1000-patient, phase 3
trials in assessing biosimilarity and therapeutic equivalence, under the
condition that the administered biosimilar given to individual patients can be
clearly identified. Obviously, there will probably never be a "one size fits all"
development model, and an individualized, risk-based approach to biosimilar
development will always have to be considered and discussed early with
regulators.
PMID- 29943089
TI - Self-inflicted long bone fractures for insurance fraud.
AB - Self-inflicted fractures simulating traffic accident represent a new social fraud
opportunity for criminality. Recognising scams through an increase of awareness
of existence of self-inflicted arm fractures for insurance fraud could help
community health workers to report these injuries to the competent authorities.
In this article, authors have recognised an unusual but consistent pattern of
upper and lower limb fractures whose incidence does not coincide in numerical
terms with what is reported in literature. The aim of the present study is to
describe fracture patterns observed over the past 2 years. Further, authors
describe clinical presentations of these fractures and attempt to define a
possible mechanism of these types of injuries.
PMID- 29943090
TI - Local Application of Pyrophosphorylated Simvastatin Prevents Experimental
Periodontitis.
AB - PURPOSE: Simvastatin (SIM), a HMG-CoA reductase inhibitor widely prescribed for
hypercholesterolemia, has been reported to ameliorate inflammation and promote
osteogenesis. Its clinical applications on these potential secondary indications,
however, have been hampered by its lack of osteotropicity and poor water
solubility. To address this challenge, we propose to design and evaluate the
therapeutic efficacy of a novel simvastatin prodrug with better water solubility
and bone affinity. METHOD: The prodrug (SIM-PPi) was synthesized by directly
conjugating a SIM trimer to a pyrophosphate (PPi). It was characterized and
evaluated in vitro for its water solubility, osteotropicity, toxicity, anti
inflammatory and osteoinductive properties. It was then tested for anti
inflammatory and osteoinductive properties in vivo by three weekly injections
into gingiva of a ligature-induced experimental periodontitis rat model. RESULTS:
In vitro studies showed that SIM-PPi has greatly improved water-solubility of SIM
and shows strong binding to hydroxyapatite (HA). In macrophage culture, SIM-PPi
inhibited LPS-induced pro-inflammatory cytokines (IL-1beta, IL-6). In osteoblast
culture, it was found to significantly increase alkaline phosphatase (ALP)
activity with accelerated mineral deposition, confirming the osteogenic potential
of SIM-PPi. When tested in vivo on an experimental periodontal bone-loss model,
SIM-PPi exhibited a superior prophylactic effect compared to dose equivalent SIM
in reducing inflammatory cells and in preserving alveolar bone structure, as
shown in the histological and micro-CT data. CONCLUSION: SIM-PPi may have the
potential to be further developed for better clinical management of bone loss
associated with periodontitis.
PMID- 29943091
TI - Correction to: Transposable Elements Activity is Positively Related to Rate of
Speciation in Mammals.
AB - The original version of the article unfortunately contained tagging error in
Given and Surname of all the authors.
PMID- 29943092
TI - Dl-3-n-Butylphthalide improves lipopolysaccharide-induced depressive-like
behavior in rats: involvement of Nrf2 and NF-kappaB pathways.
AB - RATIONALE AND OBJECTIVES: Dl-3-n-Butylphthalide (NBP), a small molecule compound
extracted from the seeds of Apium graveolens, possesses a large range of
biological effects. Here, we attempted to explore the therapeutic effects of NBP
on lipopolysaccharide (LPS)-induced major depressive disorder (MDD) and gain
further insight into the underlying mechanisms of the antidepressant effects of
NBP. METHODS: We evaluated the effect of NBP against LPS-induced behavioral
changes in rats. We also examined the inflammation, oxidative stress, and
apoptosis markers and analyzed the Nrf2 and NF-kappaB pathways in the hippocampus
of rats following repeated peripheral immune challenge by LPS for 2 weeks (500
MUg/kg every other day). RESULTS: Our results indicated that repeated LPS
administration induced the rats to a depressive-like state and activated
inflammatory response, oxidative stress, and apoptosis reactions in the
hippocampus. NBP treatment attenuated the LPS-induced abnormal behavior and
ameliorated pathogenic processes in rats with MDD. NBP reduced the inflammatory
response with inhibited expression of pro-inflammatory cytokines including IL
1beta and IL-6 and downregulated the NF-kappaB signal pathway. Concurrent with
the anti-inflammation action, NBP reduced LPS-induced oxidative reactions in the
hippocampus and enhanced Nrf2-targeted signals, as evidenced by increased
transcription of antioxidant enzymes and decreased malondialdehyde (MDA)
production. In addition, NBP inhibited LPS-induced neuronal apoptosis in the rat
brain, as evidenced by decreased apoptosis marker Caspase-3 production and TUNEL
assay. CONCLUSIONS: These results provide more insight into pathogenesis of MDD
and firstly demonstrated the potential antidepressant actions of NBP.
PMID- 29943094
TI - Dutch Adolescents' Everyday Expressions of Sexual Behavior Trajectories Over a 2
Year Period: A Mixed-Methods Study.
AB - Using an extended definition of sexuality, this mixed-methods study builds on
existing research into adolescents' emergent sexual development by longitudinally
examining adolescents' sexual behavior trajectories (i.e., from less to more
intimate sexual behavior). Over a 2-year period, 45 adolescents (M age = 15.9
years) reported on their sexual behavior using questionnaires and on their
everyday expressions of sexuality in the form of semi-structured diaries. Cluster
analysis using the questionnaire data identified three sexual behavior
trajectories: a non-sexually active trajectory (meaning no or minor sexual
behavior) (n = 29), a gradually sexually active trajectory (meaning step-by-step
sexual behavior development) (n = 12), and a fast sexually active trajectory
(meaning rapid sexual behavior development) (n = 4). Qualitative analysis using
diaries revealed the following themes: romantic versus sex-related topics,
desires, uncertainties, and references to the social context. In general, all
adolescents reported more about romantic aspects of sexuality (than about sexual
acts) in the diaries, regardless of their sexual behavior trajectory. Sexually
active adolescents (i.e., gradual and fast) were more concerned with sexuality in
their diaries, especially more with the physical aspects of sexuality, than non
active adolescents. Gradual adolescents experienced more desires about physical
sexual contact and reported fewer references to their social network than non
active and fast adolescents. The findings suggest that sexual education that
discusses the internal experiences of sexuality, such as feelings and thoughts,
particularly the romantic aspects, may help adolescents process their preferences
for different sexual and romantic acts and may contribute to healthy sexual
development.
PMID- 29943093
TI - The effect of dopamine on conditioned placebo analgesia in healthy individuals: a
double-blind randomized trial.
AB - RATIONALE: Better means to control placebo effects are key to optimizing
treatment outcomes. Dopamine-based reward and learning mechanisms have been
hypothesized to drive placebo effects. Here, we tested whether dopamine
augmentation can modulate learned placebo effects. METHODS: We performed a
randomized, double-blind parallel group study with 70 healthy adult participants
to test whether a single oral dose of the dopamine precursor levodopa/carbidopa
(100/25 mg) administered before the acquisition of conditioned placebo analgesia
enhances the placebo response in an established experimental placebo model using
heat pain. RESULTS: Overall, the observed levels of placebo analgesia in our
sample were low and not statistically significant. Levodopa, compared to placebo,
only led to a marginal increase in placebo analgesia. Female participants tended
to show larger placebo responses than male participants. Within the female
subgroup, levodopa showed small-to-moderate effects on placebo analgesia;
however, this effect was not statistically significant. CONCLUSIONS: In summary,
the present study could not provide evidence for a placebo augmenting effect of
levodopa-enhanced dopamine levels in healthy subjects. Further studies are needed
to elucidate whether placebo enhancement can be achieved through dopamine
augmentation.
PMID- 29943095
TI - Collective Sex Environments Without the Sex? Insights from the BDSM Community.
PMID- 29943096
TI - Climate variability decreases species richness and community stability in a
temperate grassland.
AB - Climate change involves modifications in both the mean and the variability of
temperature and precipitation. According to global warming projections, both the
magnitude and the frequency of extreme weather events are increasing, thereby
increasing climate variability. The previous studies have reported that climate
warming tends to decrease biodiversity and the temporal stability of community
primary productivity (i.e., community stability), but the effects of the
variability of temperature and precipitation on biodiversity, community
stability, and their relationship have not been clearly explored. We used a long
term (from 1982 to 2014) field data set from a temperate grassland in northern
China to explore the effects of the variability of mean temperature and total
precipitation on species richness, community stability, and their relationship.
Results showed that species richness promoted community stability through
increases in asynchronous dynamics across species (i.e., species asynchrony).
Both species richness and species asynchrony were positively associated with the
residuals of community stability after controlling for its dependence on the
variability of mean temperature and total precipitation. Furthermore, the
variability of mean temperature reduced species richness, while the variability
of total precipitation decreased species asynchrony and community stability.
Overall, the present study revealed that species richness and species asynchrony
promoted community stability, but increased climate variability may erode these
positive effects and thereby threaten community stability.
PMID- 29943097
TI - Evaluation of the effects of sensorimotor exercise on physical and psychological
parameters in breast cancer patients undergoing neurotoxic chemotherapy.
AB - INTRODUCTION: Breast cancer is the most common cancer disease of women in
industrialized countries. Neurotoxic chemotherapy drugs are known to harm
peripheral nerves and cause a chemotherapy-induced peripheral neuropathy (CIPN).
CIPN is one of the most common adverse events associated with Paclitaxel
chemotherapy and may remain present long after the termination of chemotherapy.
Thus, it reduces the patients' quality of life (QoL) both during chemotherapy and
onwards, and can impose a danger on breast cancer survivors due to an increased
risk of falling and fall-related injuries. METHODS: The aim of this randomized
controlled trial (RCT) (n = 36) (IG: intervention group, n = 17) (CG: control
group, n = 19) was to determine whether sensorimotor exercises have a positive
effect on physical and psychological parameters in breast cancer patients
undergoing neurotoxic chemotherapy (Paclitaxel). RESULTS: As a result, we were
able to show significant improvements in postural stability in monopedal stance
[left leg 16.17 +/- 3.67 vs. 21.55 +/- 5.33 (p < 0.001) and right leg 15.14 +/-
2.30 vs. 20.85 +/- 5.05 (p < 0.001)] and in bipedal stance [T1 vs. T0, - 0.49
(IG) vs. + 1.14 (CG) p = 0.039]. DISCUSSION: These results in posturography
correlate with the clinical presentation with intervention group patients scoring
significantly better on the Fullerton Advanced Balance Scale [37.71 +/- 2.73 vs.
34.47 +/- 3.98 (p = 0.004)]. Moderate strength training successfully prevented a
strength loss in the IG that was remarkable in the CG (- 1.60 vs. 0.60, p =
0.029). Concerning the psychological parameters assessed via EORTC- and MFI
questionnaires, no significant improvements were found. CONCLUSION: Future
studies should focus on the correlation of clinical and posturometry findings and
subjective QOL such as the long-term-development of CIPN.
PMID- 29943099
TI - Granular corneal dystrophy: an enigma resolved.
AB - PURPOSE: To report the intra-familial phenotypic variation of granular corneal
dystrophy (GCD) across different age groups. METHOD: Two cases of GCD belonging
to the same family (mother and daughter) were assessed and clinical findings were
noted. RESULT: An 18-year-old female with complaint of glare, on examination
showed brownish granules involving bowman's layer and superficial corneal stroma
suggesting a diagnosis of Bowman layer dystrophy. Screening of her mother
revealed multiple diffuse white granular opacities with snowflake appearance
involving the central cornea. The intervening cornea was clear and limbus was not
involved. Focal illumination showed deep stromal involvement. All these findings
were typical of GCD. Genetic analysis revealed mutation of TGF beta-1 located on
5q31 which was consistent with our clinical diagnosis of GCD. CONCLUSION:
Variable clinical presentation of GCD in different age groups can lead to
diagnostic dilemma. Screening of family members can be helpful especially when
dealing with early cases of GCD.
PMID- 29943100
TI - Evaluation of the effect of combined intravitreal ranibizumab injection and sub
tenon steroid injection in the treatment of resistant diabetic macular edema.
AB - PURPOSE: To compare sub-tenon steroid plus anti-VEGF injection with anti-VEGF
injection solely in the treatment of resistant diabetic macular edema (DME).
METHOD: Patients who exhibited insufficient anatomic [over 350 MUm central
macular thickness (CMT)] and less than 3 lines of visual gain at least six anti
VEGF injections, were randomly divided into two groups. In group I, the anti-VEGF
injection was performed 10 days after the sub-tenon steroid injection
[Triamcinolone acetonide (Sinakort-A(r))]. And anti-VEGF was performed when
needed during the follow-up period. In group II, treatment was continued with
anti-VEGF only. All patients' visual acuity and CMT were followed up for 6
months. RESULTS: The baseline BCVA in group I and group II was 0.51 +/- 0.667
logMAR and 0.47 +/- 0.60 logMAR, respectively (p = 0.52). In group I and II, at
the end of 6-month follow-up, BCVA improved to 0.38 +/- 0.60 logMAR (p < 0.001)
and 0.43 +/- 0.60 logMAR (p = 0.20), respectively. The baseline CMT in group I
and group II was 494 +/- 118.32 and 438.20 +/- 90.99 MUm, respectively (p =
0.029). In group I and II, at the end of 6 months, CMT decreased to 302.57 +/-
69.89 MUm (p < 0.001) and 439.20 +/- 107.6 MUm (p = 0.96), respectively.
CONCLUSION: Adding steroid to routine anti-VEGF treatment is an effective way of
treatment method for resistant DME.
PMID- 29943098
TI - Exploration of intrinsic brain activity in migraine with and without comorbid
depression.
AB - BACKGROUND: Major depressive disorder is a common comorbidity in migraineurs.
Depression may affect the progression and prognosis of migraine. Few studies have
examined the brain function in migraineurs that may cause this comorbidity. Here,
we aimed to explore depression-related abnormalities in the intrinsic brain
activity of interictal migraineurs with comorbid depression using resting-state
functional magnetic resonance imaging. RESULTS: Significant main effects of
migraine and depression provided evidence that migraine and depression jointly
affected the left medial prefrontal cortex, which was thought to be the neural
basis of self-referential mental activity in previous studies. Abnormalities in
this region may contribute to determining the common symptoms of migraine and
depression and even result in comorbidity. Additionally, migraineurs with
comorbid depression had different developmental trajectories in the right
thalamus and fusiform, which were associated with recognizing, transmitting,
controlling and remembering pain and emotion. CONCLUSIONS: Based on our findings,
the abnormal mPFC which may contribute to determining the common symptoms in
migraine and depression and may be a therapeutic target for migraineurs comorbid
depression. The different developmental trajectory in thalamus and fusiform
indicates that the comorbidity may arise through a specific mechanism rather than
simple superposition of migraine and depression.
PMID- 29943101
TI - ERK1/2 regulates heat stress-induced lactate production via enhancing the
expression of HSP70 in immature boar Sertoli cells.
AB - Lactate produced by Sertoli cells plays an important role in spermatogenesis, and
heat stress induces lactate production in immature boar Sertoli cells.
Extracellular signaling regulated kinase 1 and 2 (ERK1/2) participates in heat
stress response. However, the effect of ERK1/2 on heat stress-induced lactate
production is unclear. In the present study, Sertoli cells were isolated from
immature boar testis and cultured at 32 degrees C. Heat stress was induced in a
43 degrees C incubator for 30 min. Proteins and RNAs were detected by western
blotting and RT-PCR, respectively. Lactate production and lactate dehydrogenase
(LDH) activity were detected using commercial kits. Heat stress promoted ERK1/2
phosphorylation, showing a reducing trend with increasing recovery time. In
addition, heat stress increased heat shock protein 70 (HSP70), glucose
transporter 3 (GLUT3), and lactate dehydrogenase A (LDHA) expressions, enhanced
LDH activity and lactate production at 2-h post-heat stress. Pretreatment with
U0126 (1 * 10-6 mol/L), a highly selective inhibitor of ERK1/2 phosphorylation,
reduced HSP70, GLUT3, and LDHA expressions and decreased LDH activity and lactate
production. Meanwhile, ERK2 siRNA1 reduced the mRNA level of ERK2 and weakened
ERK1/2 phosphorylation. Additionally, ERK2 siRNA1 reduced HSP70, GLUT3, and LHDA
expressions decreased LDH activity and lactate production. Furthermore, HSP70
siRNA3 downregulated GLUT3 and LDHA expressions and decreased LDH activity and
lactate production. These results show that activated ERK1/2 increases heat
stress-induced lactate production by enhancing HSP70 expression to promote the
expressions of molecules related to lactate production (GLUT3 and LDHA). Our
study reveals a new insight in reducing the negative effect of heat stress in
boars.
PMID- 29943102
TI - Height, waist circumference, body mass index, and body somatotype across the life
course and risk of glioma.
AB - PURPOSE: Recent studies have suggested height as a risk factor for glioma, but
less is known regarding body mass index (BMI) or other anthropomorphic measures.
We evaluated the association between body habitus and risk of glioma. METHODS: We
evaluated the association of measures of height, BMI, waist circumference, and
somatotypes with risk of glioma in two prospective cohorts, the Nurses' Health
Study and the Health Professionals Follow-Up Study. RESULTS: We documented 508
incident cases of glioma (321 glioblastoma [GBM]). In both cohorts, we found no
significant association between adult BMI or waist circumference and risk of
glioma, with pooled HR for BMI of 1.08 (95% CI 0.85-1.38 comparing >= 30 to < 25
kg/m2) and for waist circumference of 1.05 (95% CI 0.80-1.37 highest vs. lowest
quintile). Higher young adult BMI (at age 18 in NHS and 21 in HPFS) was
associated with modestly increased risk of glioma in the pooled cohorts (pooled
HR 1.35, 95% CI 1.06-1.72 comparing >= 25 kg/m2 vs. less; HR 1.34 for women and
1.37 for men). Analysis of body somatotypes suggested reduced risk of glioma
among women with heavier body types at all ages this measure was assessed (HRs
ranging from 0.52 to 0.65 comparing highest tertile to lowest tertile), but no
significant association among men. Height was associated with increased risk of
glioma among women (HR 1.09, 95% CI 1.04-1.14 per inch), but not significantly
among men. Within the 8 years prior to diagnosis, cases had no material weight
loss compared to non-cases. All results were similar when limited to GBM.
CONCLUSION: Adult BMI and waist circumference were not associated with glioma.
Higher BMI at age 21 for men and at age 18 for women was modestly associated with
risk in the pooled cohort. Based on body somatotypes, however, women with heavier
body types during childhood and young adulthood may be at lower risk of glioma,
although this association was not observed later in life with measurements of
BMI. Greater height was associated with increased risk, and the trend was more
pronounced in women.
PMID- 29943104
TI - Presentation of central precocious puberty in two patients with Tay-Sachs
disease.
AB - Tay-Sachs disease is an autosomal recessive type of lysosomal storage disorder.
The disease is very rare in Turkey, with an incidence of 0.54/100,000. The
clinical manifestations of Tay-Sachs disease include progressive developmental
delay, seizures, deafness, blindness, spasticity, and dystonia, which are caused
by the accumulation of gangliosides in the central nervous system. To date, only
one case indicating the association between Tay-Sachs disease and central
precocious puberty has been reported. Although the mechanism of this association
is not clear, it is thought to be due to ganglioside accumulation in the central
nervous system or the inhibition of the hypothalamic inhibiting pathway. Herein,
we report two patients with genetically proven Tay-Sachs disease who developed
central precocious puberty during follow-up. Pubertal development in patients
affected by Tay-Sachs disease should be carefully assessed.
PMID- 29943103
TI - Maternal Anthropometry and Its Relationship with the Nutritional Status of
Vitamin D, Calcium, and Parathyroid Hormone in Pregnant Women After Roux-en-Y
Gastric Bypass.
AB - OBJECTIVE: To assess the influence of pre-pregnancy body mass index (BMI), total
gestational weight gain (TGWG), and pre-pregnancy surgical success on the
nutritional status of vitamin D, calcium, and parathyroid hormone (PTH) in the
trimesters of pregnancy of women who previously underwent Roux-en-Y gastric
bypass (RYGB). METHODOLOGY: This is an analytical, longitudinal, and
retrospective study comprising 42 pregnant women who previously underwent RYGB.
Concentrations of vitamin D3, calcium, and PTH were assessed in all trimesters.
Anthropometric variables necessary for calculating TGWG, surgical success, and
BMI were collected preoperatively and over the trimesters of pregnancy. RESULTS:
A total of 97.1% had vitamin D3 inadequacy at some point in pregnancy. Pre
pregnancy BMI, even when classified as overweight, may have exacerbated the serum
concentrations of this vitamin in the third trimester (p = 0.011), and it was
significantly lower in women with normal weight and/or obesity (p = 0.039). It
was evidenced that both pre-pregnancy BMI and TGWG above the recommended optimal
weight can be associated with calcium homeostasis, especially early in pregnancy.
It was also shown that surgical success in the pre-pregnancy period may have
influenced the serum concentrations of vitamin D in the second trimester of
pregnancy (p = 0.013). CONCLUSION: This study draws attention to the importance
of monitoring the nutritional status of vitamin D3 and calcium in the prenatal
period due to its relationship with pre-pregnancy BMI, TGWG, and surgical
success.
PMID- 29943105
TI - Application of a Volumetric Absorptive Microsampling Device to a Pharmacokinetic
Study of Tacrolimus in Rats: Comparison with Wet Blood and Plasma.
AB - BACKGROUND AND OBJECTIVES: Volumetric absorptive microsampling (VAMS) devices are
useful for sampling a smaller volume of blood from rodents in the preclinical
setting. In the present study, we evaluated the proof of concept of a VAMS device
by comparing the pharmacokinetic data of tacrolimus in rats among dried blood in
VAMS, wet blood, and plasma. METHODS: Tacrolimus was administered orally, to
rats, at a dose of 10 mg/kg. Only 10 MUL aliquots of blood were absorbed by VAMS
devices at designated time points. Tacrolimus was extracted with a methanol-water
mixture (1:1, v/v) via sonication. Tacrolimus levels in wet blood (10 MUL) and
plasma (10 MUL) were quantified after protein precipitation. RESULTS: Tacrolimus
in VAMS devices was quantifiable from 0.2 ng/mL using high-performance liquid
chromatography with tandem mass spectrometer. Accuracy and precision were within
the acceptance criteria. Bland-Altman plots showed that tacrolimus concentrations
in VAMS devices were similar to those in wet blood, regardless of tacrolimus
levels. On the other hand, tacrolimus levels in plasma were different from those
in VAMS devices, especially at lower concentrations, likely due to partition of
tacrolimus to blood cells. However, pharmacokinetic parameters were comparable
among the three matrices. CONCLUSIONS: Collectively, these findings suggest that
the VAMS device can be a useful device for pharmacokinetic studies in rats.
PMID- 29943106
TI - Knowledge.
PMID- 29943107
TI - Third Year of Survey Data Shows Continuing Benefits of Medicaid Expansions for
Low-Income Childless Adults in the U.S.
AB - BACKGROUND: The Affordable Care Act (ACA) of 2010 incentivized states to expand
eligibility for their Medicaid programs. Many did so in 2014, and there has been
great interest in understanding the effects of these expansions on access to
health care, health care utilization, and population health. OBJECTIVE: To
estimate the longer-term (three-year) impact of Medicaid expansions on insurance
coverage, access to care, preventive care, self-assessed health, and risky health
behaviors. DESIGN: A difference-in-differences model, exploiting variation across
states and over time in Medicaid expansion, was estimated using data from the
Behavioral Risk Factor Surveillance System (BRFSS) for 2010-2016. PARTICIPANTS:
Low-income childless adults aged 19-64 years in the BRFSS. MAIN MEASURES:
Outcomes included insurance coverage, access to care, several forms of preventive
care (e.g., routine checkups, flu shots, HIV tests, dental visits, and cancer
screening), risky health behaviors (e.g., smoking, alcohol abuse, obesity), and
self-assessed health. KEY RESULTS: The previously documented benefits of Medicaid
expansions on insurance coverage, access to care, preventive care, and self
assessed health have persisted 3 years after expansion. There was no detectable
effect on risky health behaviors. CONCLUSIONS: The Affordable Care Act was
motivated in part by a desire to increase health insurance coverage, improve
access to care, and increase use of preventive care. The Medicaid expansions
facilitated by the ACA are helping to achieve those objectives, and the benefits
have persisted 3 years after expansion.
PMID- 29943108
TI - Breakdowns on the information highway during inter-hospital patient transfers.
PMID- 29943111
TI - On the necessity of careful interpretation of omics data.
PMID- 29943109
TI - Comparative Effectiveness of Usual Care With or Without Chiropractic Care in
Patients with Recurrent Musculoskeletal Back and Neck Pain.
AB - BACKGROUND: Chiropractic care is a popular alternative for back and neck pain,
with efficacy comparable to usual care in randomized trials. However, the
effectiveness of chiropractic care as delivered through conventional care
settings remains largely unexplored. OBJECTIVE: To evaluate the comparative
effectiveness of usual care with or without chiropractic care for patients with
chronic recurrent musculoskeletal back and neck pain. STUDY DESIGN: Prospective
cohort study using propensity score-matched controls. PARTICIPANTS: Using
retrospective electronic health record data, we developed a propensity score
model predicting likelihood of chiropractic referral. Eligible patients with back
or neck pain were then contacted upon referral for chiropractic care and enrolled
in a prospective study. For each referred patient, two propensity score-matched
non-referred patients were contacted and enrolled. We followed the participants
prospectively for 6 months. MAIN MEASURES: Main outcomes included pain severity,
interference, and symptom bothersomeness. Secondary outcomes included
expenditures for pain-related health care. KEY RESULTS: Both groups' (N = 70
referred, 139 non-referred) pain scores improved significantly over the first 3
months, with less change between months 3 and 6. No significant between-group
difference was observed. (severity - 0.10 (95% CI - 0.30, 0.10), interference -
0.07 (- 0.31, 0.16), bothersomeness - 0.1 (- 0.39, 0.19)). After controlling for
variances in baseline costs, total costs during the 6-month post-enrollment
follow-up were significantly higher on average in the non-referred versus
referred group ($1996 [SD = 3874] vs $1086 [SD = 1212], p = .034). Adjusting for
differences in age, gender, and Charlson comorbidity index attenuated this
finding, which was no longer statistically significant (p = .072). CONCLUSIONS:
We found no statistically significant difference between the two groups in either
patient-reported or economic outcomes. As clinical outcomes were similar, and the
provision of chiropractic care did not increase costs, making chiropractic
services available provided an additional viable option for patients who prefer
this type of care, at no additional expense.
PMID- 29943110
TI - Hepatocyte SHP deficiency protects mice from acetaminophen-evoked liver injury in
a JNK-signaling regulation and GADD45beta-dependent manner.
AB - Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver
failure. Prolonged c-Jun N-terminal kinase (JNK) activation plays a central role
in APAP-induced liver injury; however, growth arrest and DNA damage-inducible 45
beta (GADD45beta) is known to inhibit JNK phosphorylation. The orphan nuclear
receptor small heterodimer partner (SHP, NR0B2) acts as a transcriptional co
repressor of various genes. The aim of the present study was to investigate the
role of SHP in APAP-evoked hepatotoxicity. We used lethal (750 mg/kg) or
sublethal (300 mg/kg) doses of APAP-treated wild-type (WT), Shp knockout (Shp-/
), hepatocyte-specific Shp knockout (Shphep-/-), and Shp and Gadd45beta double
knockout (Shp-/-Gadd45beta-/-) mice for in vivo studies. Primary mouse
hepatocytes were used for a comparative in vitro study. SHP deficiency protected
against APAP toxicity with an increased survival rate, decreased liver damage,
and inhibition of prolonged hepatic JNK phosphorylation in mice, which was
independent of APAP metabolism regulation. Furthermore, Shphep-/- mice showed
diminished APAP hepatotoxicity compared with WT mice. SHP-deficient primary mouse
hepatocytes also showed decreased cell death and inhibition of sustained JNK
phosphorylation following toxic APAP treatment. While SHP expression declined,
GADD45beta expression increased after APAP treatment in WT mice. In Shp-/- mice,
APAP-evoked GADD45beta induction was significantly enhanced. Notably, the
ameliorative effects of SHP deficiency on APAP-induced liver injury were
abolished in Shp-/-Gadd45beta-/- mice. The current study is the first to
demonstrate that hepatocyte-specific SHP deficiency protects against APAP
overdose-evoked hepatotoxicity in a JNK signaling regulation and GADD45beta
dependent manner. SHP is suggested to be a novel therapeutic target for APAP
overdose treatment.
PMID- 29943112
TI - Novel approach to integrated DNA adductomics for the assessment of in vitro and
in vivo environmental exposures.
AB - Adductomics is expected to be useful in the characterization of the exposome,
which is a new paradigm for studying the sum of environmental causes of diseases.
DNA adductomics is emerging as a powerful method for detecting DNA adducts, but
reliable assays for its widespread, routine use are currently lacking. We propose
a novel integrated strategy for the establishment of a DNA adductomic approach,
using liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ
MS/MS), operating in constant neutral loss scan mode, screening for both known
and unknown DNA adducts in a single injection. The LC-QqQ-MS/MS was optimized
using a representative sample of 23 modified 2'-deoxyribonucleosides reflecting a
range of biologically relevant DNA lesions. Six internal standards (ISTDs) were
evaluated for their ability to normalize, and hence correct, possible variation
in peak intensities arising from matrix effects, and the quantities of DNA
injected. The results revealed that, with appropriate ISTDs adjustment, any bias
can be dramatically reduced from 370 to 8.4%. Identification of the informative
DNA adducts was achieved by triggering fragmentation spectra of target ions. The
LC-QqQ-MS/MS method was successfully applied to in vitro and in vivo studies to
screen for DNA adducts formed following representative environmental exposures:
methyl methanesulfonate (MMS) and five N-nitrosamines. Interestingly, five new
DNA adducts, induced by MMS, were discovered using our adductomic approach-an
added strength. The proposed integrated strategy provides a path forward for DNA
adductomics to become a standard method to discover differences in DNA adduct
fingerprints between populations exposed to genotoxins, and facilitate the field
of exposomics.
PMID- 29943114
TI - What is the cause of P-wave undersensing in this CRT-D device?
PMID- 29943113
TI - iTRAQ-based quantitative proteomic analysis reveals dynamic changes during
daylily flower senescence.
AB - MAIN CONCLUSION: Sugar-related metabolic biological processes and metabolic
pathways as well as invertase, protease, and ribosomal proteins may be critical
regulators controlling the circadian rhythm and ephemeral properties of daylily
flowers. Daylily is a familiar perennial flower. The daylily flower opens at dawn
and withers away at night. Flower longevity in almost all daylily varieties from
opening to fading is less than 24 h. In the past decades, the physiological
changes and genetic responses to senescence in daylily flowers have been
reported. However, the main metabolic pathways and biological processes involved
in daylily flower senescence and the proteins involved in premature senility of
daylily flowers are poorly understood. Herein, we identified differences between
the proteomes of four developmental stages (s1-s4) of daylily flowers using iTRAQ
based quantitative proteomic methods. A total of 445 proteins (containing at
least two unique peptides) were identified, and differentially expressed proteins
(upregulation >= 1.5 or downregulation <= 0.67, P value <= 0.05) were detected
between these stages in the following numbers: 58 (s2/s1), 59 (s3/s1), 31
(s3/s2), 64 (s4/s1), 52 (s4/s2), and 29 (s4/s3). Protein functions and
classifications were analyzed based on GO, KEGG, and COG, and expressive
hierarchical cluster analysis and functional enrichment analysis for
differentially expressed proteins were carried out. A comparison of the late
stages (s3 and s4) with the early stage (s1) revealed that the sugar (hexose,
monosaccharide, and glucose) metabolic process GO category was the most enriched,
and sugar (galactose, pentose, starch, and sucrose) metabolism pathways
constituted the most enriched KEGG category. Finally, the potential research
value of invertase, protease, and ribosomal proteins for revealing the mechanism
underlying the circadian rhythm and ephemeral properties of daylily flowers are
discussed. These data and analyses provide new insight into the senescence
mechanism of daylily flowers.
PMID- 29943116
TI - Coronary pressure-derived parameters.
PMID- 29943115
TI - Transcatheter aortic valve replacement with the 34 mm Medtronic Evolut valve :
Early results of single institution experience.
AB - OBJECTIVES: To report our experience with the recently introduced 34 mm Evolut
transcatheter aortic valve replacement (TAVR) prosthesis. BACKGROUND: A larger
TAVR prosthesis has become available for the treatment of aortic stenosis (AVS)
in larger native aortic annuli (up to 30 mm). Outcomes with this new device are
still unreported. RESULTS: The first 25 transfemoral TAVRs performed by our team
with the self-expandable 34 mm Evolut are presented. The majority of patients
were male (84%) with a mean age of 81.3 +/- 5.6 years, a median logistic euro
SCORE of 14.7 (5.4-61.0), and a computed tomography measured mean perimeter
derived aortic annulus diameter of 27.1 +/- 1.4 mm (min. 25.0-max. 31.2 mm). We
implanted one 34 mm Evolut in all patients. Median operative time and radiation
time were 68.5 and 12.4 min respectively. To optimise final valve position and
haemodynamic performance, at least one complete re-sheathing and re-positioning
of the same valve was reported in 33.2%. New permanent pacemaker implantation
(PPMI) was necessary in 28.5%. At Receiver Operating Characteristic (ROC)
analysis, a minimal diameter of the left ventricular outflow tract <21.9 mm was a
significant predictor for PPMI (specificity 82%; sensitivity 83%; p = 0.005; Area
Under the Curve (AUC) = 0.9). Length of stay in hospital was 9.2 +/- 5.8 days and
no in-hospital death was reported. At discharge, grade 1 + para-valvular
regurgitation was present in 32%, and no regurgitation in the remaining patients.
Device success and early safety were 100% and 92% respectively. CONCLUSIONS: TAVR
with the 34 mm Evolut prosthesis has shown satisfactory acute outcomes. Although
results are consistent with those observed with smaller Evolut prostheses, a
trend for a higher PPMI rate has been noticed and could derive from a higher
oversizing rate.
PMID- 29943117
TI - Trends in patient characteristics and clinical outcome over 8 years of
transcatheter aortic valve implantation.
AB - AIM: In the evolving field of transcatheter aortic valve implantations (TAVI) we
aimed to gain insight into trends in patient and procedural characteristics as
well as clinical outcome over an 8-year period in a real-world TAVI population.
METHODS: We performed a single-centre retrospective analysis of 1,011 consecutive
patients in a prospectively acquired database. We divided the cohort into
tertiles of 337 patients; first interval: January 2009-March 2013, second
interval: March 2013-March 2015, third interval: March 2015-October 2016.
RESULTS: Over time, a clear shift in patient selection was noticeable towards
lower surgical risks including Society of Thoracic Surgeons predicted risk of
mortality score and comorbidity. The frequency of transfemoral TAVI increased
(from 66.5 to 77.4%, p = 0.0015). Device success improved (from 62.0 to 91.5%, p
< 0.0001) as did the frequency of symptomatic relief (>=1 New York Heart
Association class difference) (from 73.8 to 87.1%, p = 0.00025). Complication
rates decreased, including in-hospital stroke (from 5.0 to 2.1%, p = 0.033) and
pacemaker implantations (from 10.1 to 5.9%, p = 0.033). Thirty-day mortality
decreased (from 11.0 to 2.4%, p < 0.0001); after adjustment for patient
characteristics, a mortality-risk reduction of 72% was observed (adjusted hazard
ratio [HR]: 0.28, 95% confidence interval [CI]: 0.13-0.62). One-year mortality
rates decreased (from 23.4 to 11.4%), but this was no longer significant after a
landmark point was set at 30 days (mortality from 31 days until 1 year) (adjusted
HR: 0.69, 95% CI: 0.41-1.16, p = 0.16). CONCLUSION: A clear shift towards a lower
risk TAVI population and improved clinical outcome was observed over an 8-year
period. Survival after TAVI improved impressively, mainly as a consequence of
decreased 30-day mortality.
PMID- 29943118
TI - Correction to: Depression literacy and health-seeking attitudes in the Western
Pacific region: a mixed-methods study.
AB - In the original publication of this article, Acknowledgements Section was not
included. The Acknowledgements are given below. The original article has been
corrected.
PMID- 29943119
TI - [Neoadjuvant chemoradiotherapy for rectal cancer : Results of the OCUM study].
PMID- 29943120
TI - Development and validation of a formula based on maxillary sinus measurements as
a tool for sex estimation: a cone beam computed tomography study.
AB - BACKGROUND: As sex estimation is an important step to delineate the biological
profile, the development of tools employing anatomical structures which may
maintain their integrity even after extreme events, such as the maxillary sinus,
become useful for forensic identification. Thus, the aim in the present study was
to develop and validate a formula for sex estimation through measurements in the
maxillary sinuses in a Brazilian population, using cone beam computed tomography
(CBCT) scans. MATERIAL AND METHODS: Linear and volumetric measurements in the
maxillary sinus were performed bilaterally in 94 CBCT scans from 45 males (mean
age 25.2 +/- 0.79) and 49 females (mean age 23.7 +/- 0.50). The OnDemand 3D
software was employed for linear measurements (height, length and width of, and
the largest distance between the right and left maxillary sinuses), while the ITK
SNAP 3.0 segmentation software was used to acquire the volume. The data obtained
was applied to a mathematical model for sex estimation. To validate the developed
formula, another sample composed of 60 CBCT images of Brazilian individuals was
tested. RESULTS: Overall, maxillary sinuses' measurements were significantly
higher in males, without statistically significant differences between the right
and left sides within each group. The most dimorphic measurement was the height,
with an accuracy of 77.7% regarding sex estimation. The formula created lead to a
sex estimation of 87.8% for females and 80% for males, with an overall accuracy
of 84%. When the formula validity was tested in another sample, it showed an
accuracy of 82.4%. CONCLUSION: The formula developed through measurements in the
maxillary sinus using CBCT scans showed an accuracy of 84% for sex estimation and
can be applied as a complementary method for human identification in the
Brazilian population.
PMID- 29943121
TI - Prediction of ovarian function recovery in young breast cancer patients after
protection with gonadotropin-releasing hormone agonist during chemotherapy.
AB - PURPOSE: This study evaluated predictive factors for recovery of ovarian function
after ovarian protection by GnRH agonist during chemotherapy in young breast
cancer patients. METHODS: This prospective cohort study analyzed 105 young breast
cancer patients who were studied longitudinally after receiving GnRH agonist
during cyclophosphamide-based chemotherapy for ovarian protection. Associations
between pretreatment hormones, clinical factors, and recovery of ovarian function
(resumption of menstruation or anti-Mullerian hormone (AMH) >= 1 ng/ml) were
evaluated at 12 months and long-term follow-up after completion of chemotherapy.
RESULTS: Mean age was 32 years (range 23-42 years). In multivariate analyses,
tamoxifen use (P = 0.035) and pretreatment follicle-stimulating hormone (FSH) (P
= 0.032) were predictive of resumption of menstruation, and age (P = 0.019),
tamoxifen use (P = 0.022), pretreatment FSH (P < 0.001), and AMH (P = 0.040) were
predictors for AMH >= 1 ng/ml at 12 months. In addition, pretreatment AMH was a
predictor for AMH >= 1 ng/ml after long-term follow-up. Receiver operating
characteristic curve analyses gave area under the curve of 0.805 for resumption
of menstruation and 0.903 for serum AMH concentration >= 1 ng/ml at 12 months,
when age, tamoxifen use, pretreatment FSH, and AMH were combined. CONCLUSION:
Pretreatment AMH (3.26 ng/ml), age (33.9 years), pretreatment FSH (5.5 IU/l), and
tamoxifen use are useful predictors for AMH >= 1 ng/ml at 12 months after GnRH
agonist. This finding will support patient and clinician decision-making
regarding fertility preservation.
PMID- 29943123
TI - Comparisons of New HIV Rapid Test Kit Performance.
AB - The development of rapid point-of-care tests for HIV infection has greatly
reduced the problem of failure to return for test results. Test manufacturers are
now developing test kits that can test for two or even three diseases at the same
time, multiple-disease test kits. This study reports on the sensitivity and
specificity of HIV tests when included on multi-disease test kits. 1029
participants were recruited from 2011 to 2014. HIV test kit sensitivities ranged
from 91.1 to 100%, and the HIV test kit specificities from 99.5 to 100%. The two
HIV kits which used oral fluid instead of blood performed well.
PMID- 29943122
TI - Chemotherapeutic Delivery from a Self-Assembling Peptide Nanofiber Hydrogel for
the Management of Glioblastoma.
AB - PURPOSE: Localized chemotherapy has gained significant impetus for the management
of malignant brain tumors. In the present study, we appraised the versatility of
an in-situ gel forming self-assembling peptide, ac-(RADA)4-CONH2, as a
biocompatible delivery depot of the chemotherapeutic drug doxorubicin (DOX) and
the anticancer agent curcumin (CUR), respectively. METHODS: The morphology and
mechanical properties of ac-(RADA)4-CONH2 were assessed with scanning electron
microscopy (SEM) and rheological studies. The in vitro drug release from ac
(RADA)4-CONH2 was monitored in phosphate-buffered saline pH 7.4. Distribution of
the fluorescent actives within the peptide matrix was visualized with confocal
laser scanning microscopy (CLSM). The in vitro biological performance of the ac
(RADA)4-CONH2-DOX and ac-(RADA)4-CONH2-CUR was evaluated on the human
glioblastoma U-87 MG cell line. RESULTS: SEM studies revealed that the ac-(RADA)4
CONH2 hydrogel contains an entangled nanofiber network. Rheology studies showed
that the more hydrophobic CUR resulted in a stiffer hydrogel compared with ac
(RADA)4-CONH2 and ac-(RADA)4-CONH2-DOX, due to the interaction of CUR with the
hydrophobic domains of the peptide nanofibers as confirmed by CLSM. In vitro
release studies showed a complete DOX release from ac-(RADA)4-CONH2 within 4 days
and a prolonged release for ac-(RADA)4-CONH2-CUR over 20 days. An increased
cellular uptake and a higher cytotoxic effect were observed for ac-(RADA)4-CONH2
DOX, compared with DOX solution. Higher levels of early apoptosis were observed
for the cells treated with the ac-(RADA)4-CONH2-CUR, compared to CUR solution.
CONCLUSIONS: The current findings highlight the potential utility of the in-situ
depot forming ac-(RADA)4-CONH2 hydrogel for the local delivery of both water
soluble and insoluble chemotherapeutic drugs.
PMID- 29943124
TI - Prevalence and Factors Associated with Contraceptive Use Among Kenyan Women Aged
15-49 Years.
AB - Uptake of contraceptives is generally low in low-income settings. For women with
HIV, contraception is a reliable and affordable method of minimizing vertical
transmission. We investigated the factors that affect contraceptive use among
Kenyan women using data collected during the Kenya Demographic & Health Survey
(KDHS) of 2014. Data on contraceptive use were extracted from the 2014 KDHS
database. Records of 31,079 Kenyan women of reproductive age (15-49 years) were
analyzed. Frequencies were calculated; cross-tabulations and bivariate and
multivariate analyses were conducted. Twelve thousand thirty-two women (39%)
reported using a contraceptive method. Region, religion, education, number of
living children, marital status, and prior testing for HIV were significantly
associated with contraceptive use among women (P < 0.001). Social, economic, and
demographic factors predict contraceptive use among Kenyan women and should be
addressed in order to increase contraceptive uptake.
PMID- 29943125
TI - Population Pharmacokinetic Analysis and Model-Based Simulations of Aripiprazole
for a 1-Day Initiation Regimen for the Long-Acting Antipsychotic Aripiprazole
Lauroxil.
AB - : BACKGROUND AND OBJECTIVES: Aripiprazole lauroxil (AL), a long-acting injectable
antipsychotic for the treatment of schizophrenia, requires 21 days of oral
aripiprazole supplementation upon initiation (21-day initiation regimen). An
alternative 1-day initiation regimen utilizing a nano-crystalline milled
dispersion of AL (ALNCD) plus a single 30 mg oral aripiprazole dose achieved
aripiprazole concentrations associated with therapeutic doses of aripiprazole in
the same time frame as the 21-day initiation regimen when starting AL (441 or 882
mg). A population pharmacokinetic (PopPK) model was developed to describe
aripiprazole pharmacokinetics following administration of ALNCD, AL and oral
aripiprazole, and evaluate dosing scenarios likely to be encountered in clinical
practice. METHODS: In total, 12,768 plasma aripiprazole concentrations from 343
patients (from 4 clinical studies) were included in the PopPK analysis and used
to construct the model. RESULTS: Concomitant administration of the 1-day
initiation regimen with all approved AL dosing regimens (441, 662, or 882 mg
monthly, 882 mg every 6 weeks, or 1064 mg every 2 months) is predicted to achieve
aripiprazole concentrations associated with therapeutic doses of AL using the 21
day initiation regimen within 4 days, maintaining these concentrations until the
next AL dose. Administration of the first AL injection 10 days after the 1-day
initiation regimen resulted in median aripiprazole concentrations just before the
second dose of AL >= 77% of that when coadministered on the same day.
Coadministration of AL with a single ALNCD injection was predicted to be
effective in rapidly re-establishing concentrations associated with therapeutic
doses of AL following dose delay. CONCLUSIONS: Model-based simulations
demonstrate that the 1-day initiation regimen is suitable for starting treatment
with all AL doses, allowing a window of <= 10 days between initiation and AL
administration. ALNCD may also be used to re-establish concentrations associated
with therapeutic doses of AL in conjunction with a delayed AL dose.
PMID- 29943126
TI - Environmentally friendly remediation of lead/cadmium co-contaminated loess soil
in northwestern China using a humificated straw solution.
AB - The remediation of heavy metal-contaminated soils is a great challenge and an
important issue for global environmental sciences and engineering. Soil washing
technology is popularly used for soil remediation, but there are issues that must
be solved. These include selecting an environmentally friendly washing solution
and preventing damage to the soil during the washing process. The aim of the
present work is to reveal the effects of operational conditions on soil
remediation contaminated by lead/cadmium, and the effects on soil physicochemical
properties caused by the washing reaction. A loess soil sample was collected from
northwestern China, and a humificated straw solution was used as the washing
solution. The remediation efficiency was investigated using a small-scale
experimental device. The remediation efficiency could be improved by optimizing
the operational conditions, and we found that the Elovich equation fits better
the reaction process compared to the double-constant equation and the first-order
kinetics equation. The washing rate of cadmium was slightly faster than that of
lead. Compared to the topsoil in the column, the concentration of lead/cadmium
was higher in the bottom soil, and the content of lead/cadmium in the inner layer
soil was lower than that in the outer layer soil. The washing process had little
influence on the surface characteristics and functional groups of soil. The
humificated straw solution could be used effectively to remove lead/cadmium and
preserve nutrients in loess soil.
PMID- 29943127
TI - Correction to: Computed Free Energies of Peptide Insertion into Bilayers are
Independent of Computational Method.
AB - The original version of the article unfortunately contained an error in NIH
support grant number RO1-GM74639 in the Acknowledgements section. The correct
grant number is RO1-GM74637. This has been corrected with this erratum.
PMID- 29943128
TI - Solid-state NMR chemical shift assignments of aquaporin Z in lipid bilayers.
AB - Aquaporin Z is the first identified prokaryotic water channel in Escherichia coli
with a high water permeability and strict substrate selectivity. Here we report
nearly complete (94% of amino acid residues) 13C and 15N chemical shift
assignments of AqpZ reconstituted in the lipid bilayers using a set of 2D and 3D
magic angle spinning solid-state NMR spectra. Secondary structure of AqpZ
predicted from chemical shift assignments is generally similar to that of X-ray
structure with a number of differences in loop and near-loop regions. The BMRB
accession number of the assignments is 27244.
PMID- 29943129
TI - Conservative management of endometrial cancer: a survey amongst European
clinicians.
AB - OBJECTIVE: To investigate differences and similarities in the clinical approach
of young clinicians managing women with endometrial cancer (EC) conservatively.
METHODS: A web-based survey was carried out. A platform of the European Network
of Young Gynaecological Oncologists (ENYGO) database was used. A 38-item multiple
choice questionnaire was used to evaluate current practice in fertility-sparing
management of EC. The survey covered investigations, treatment options, follow-up
and management of recurrence and future family planning. Descriptive statistics
were used. RESULTS: Overall, 116 out of 650 (17.84%) ENYGO members responded to
the survey. In 92 (79.3%) centres, the caseload of early stage EC treated
conservatively was less than 10 per year. One hundred and seven responders
(93.8%) believe that treatment with progestins could be offered in grade 1 EC
without myometrial invasion, but a minority would recommend it even for grade 2
tumours with no myometrial invasion or grade 1 with superficial invasion. The
diagnostic tool for establishing grade of tumour was hysteroscopy with dilatation
and curettage in 64 (55%) centres. Medroxyprogesterone acetate represents the
most commonly prescribed progestogen (55, 47.4%). In 78 (67.2%) centres, a repeat
endometrial biopsy was offered after 3 months of treatment commencement.
Recurrences are treated mostly with hysterectomy (81, 69.9%) with only a small
number of responders recommending to repeat progestin treatment. Lynch syndrome
is a contraindication for conservative management in half of the responders (57,
49.1%). Most clinicians agree that patients should be referred promptly for
assisted reproductive techniques once complete response has been achieved (68,
58.6%). CONCLUSIONS: Our study shows that conservative management is increasingly
offered to women affected by early stage EC wishing to preserve their fertility.
Further studies and joint registries are required to evaluate safety and
effectiveness of this approach in this probably growing number of patients.
PMID- 29943130
TI - How long women should be hospitalized after cesarean delivery.
AB - PURPOSE: We aimed to investigate the impact of early versus late discharge
following cesarean delivery (CD) on re-admission rate. METHODS: This is a
retrospective cohort study of all CDs performed between 2013 and 2016. Patients
who underwent CD between 01/13 and 12/14, were routinely discharged on
postoperative day (POD) 3 (early discharge) and were defined as T1 group.
Patients who had CD between 01/15 and 12/16 were routinely discharged on POD 4
(late discharge) and were defined as T2 group. Data on re-admission rate and
postpartum complications were compared between the groups. RESULTS: As compared
to the T2 group (n = 1856), less patients in the T1 group (n = 2020) had >= 2
previous CDs (13 vs. 15.6%, respectively; p = 0.02). The T1 group had shorter
operative time as compared to the T2 group (p < 0.001). Postoperative
complications and re-admission rates were similar between the groups. By logistic
regression analysis model only intrapartum complications (RR = 7.87, CI 2.45
25.26, p < 0.001) and prolonged labor (RR = 3.68, CI 1.44-9.39, p = 0.006) were
found to be independently associated with postpartum re-admission. CONCLUSIONS:
Early discharge after CD (POD 3) seems to be as safe as a more delayed discharge.
PMID- 29943131
TI - Illness perception in overweight and obesity and impact on bio-functional age.
AB - PURPOSE: Obesity is pandemic. Yet, the success of most weight loss programmes is
poor. The aim of the study was to assess illness perception in overweight/obese
people and its impact on bio-functional age (BFA) reflecting physical, mental,
emotional and social functioning. METHODS: 75 overweight/obese subjects from the
cross-sectional Bern Cohort Study 2014 were included. Participants followed a
validated "bio-functional status" test battery amended by the validated
questionnaires Patiententheoriefragebogen (illness perception) and AD-EVA (eating
and movement behaviour). BFA was calculated in subjects aged >= 35 years (n =
56). RESULTS: (1) Mental occupation with the cause of overweight/obesity was
generally moderate to high, but decreasing with age. (2) The predominant theories
for being overweight/obese were health behaviour (58.7%) and psychosocial factors
(33.3%). (3) Overweight/obese people with psychosocial theories on illness causes
were more likely to have emotional or disinhibited eating patterns. (4) Cognitive
control of eating patterns increased with age in both sexes. (5) Overweight/obese
people were still bio-functionally younger than their chronological age (8.6 +/-
0.8 year equivalents), although (6) quality of life was below average and (7) the
risk for functional pro-aging was increased in those being especially mentally
occupied with causes for overweight/obesity (r = 0.38, p < 0.001) and those
having psychosocial (r = 0.32, p < 0.05) or naturalistic theories (r = 0.47, p >
0.001). CONCLUSIONS: Consciously perceived psychosocial stress was found to be a
main factor to disturb health and promote unhealthy cognitive patterns regulating
eating and moving habits. Thus, successful weight reduction programmes should
integrate subjective illness perceptions to not only improve the therapeutic
outcome, but also functioning (BFA).
PMID- 29943132
TI - Nomogram for predicting para-aortic lymph node metastases in patients with
cervical cancer.
AB - PURPOSE: Some patients with cervical cancer may benefit from prophylactic
extended-field radiotherapy (EFRT). However, the indications for prophylactic
EFRT were unclear. In this study, we constructed a nomogram to predict para
aortic lymph node (PALN) metastases in cervical cancer. METHODS: Between January
2011 and June 2017, 1903 patients with stage IA-IVA cervical cancer received
definitive radiotherapy. Patients who were diagnosed during 2011-2015 were
assigned to a model development cohort (n = 1193) and others were assigned to a
validation cohort (n = 710). Possible predictors were analysed using logistic
regression models with model development cohort. A nomogram based on this work
was constructed and validated. RESULTS: A total of 130 patients (6.8%) suffered
from PALN metastases, with 81 patients (6.8%) in the model development cohort and
49 patients (6.9%) in the validation group. Multivariate analysis of the model
development cohort demonstrated that histology, tumour size, bilateral pelvic
lymph node (PLN) metastases, common iliac lymph node metastases and PLN
convergence or muscle involvement were significant predictive factors of PALN
metastases. The nomogram including these five factors showed good predictive
accuracy (concordance index 0.916, 95% confidence interval, CI 0.881-0.952) in
the model development cohort. In the validation cohort, the nomogram showed good
discrimination (concordance index 0.949, 95% CI 0.911-0.988) and the predicted
probability was close to the actual observed outcome. CONCLUSION: We have
developed a robust tool that is able to predict PALN metastases in patients with
cervical cancer. The nomogram could help physicians to decide whether
prophylactic EFRT should be performed for patients with cervical cancer patients.
PMID- 29943133
TI - Influence of Idiopathic Pulmonary Fibrosis Progression on Healthcare Resource
Use.
AB - BACKGROUND: Disease progression and acute exacerbations in patients with
idiopathic pulmonary fibrosis (IPF) are associated with high morbidity and
mortality. They usually require a visit to a specialist or a general practitioner
(GP) in less severe cases or hospitalisation in more severe cases. OBJECTIVE: The
objective of this study was to identify factors that influence resource use in
IPF. METHODS: Clinical and healthcare resource use data were collected in two
large, international, multi-centre, randomised controlled trials (RCTs) that
studied nintedanib for the treatment of IPF (INPULSIS-1 and -2). The pooled data
of nintedanib and placebo included 1014 patients followed for 12 months. The
trial data were analysed in 3-month intervals. We studied two dependent
variables: the occurrence of all-cause hospitalisation and visits to a physician
(GP or specialist). The independent variables included the change in forced vital
capacity percent predicted (FVC%pred), investigator-reported acute exacerbation
events, age, time since diagnosis, smoking status, and sex. RESULTS:
Hospitalisation during a 3-month interval was significantly associated with a
drop of at least 5 or 10 points in FVC%pred (odds ratios [ORs] 1.58 [p = 0.009]
and 2.62 [p < 0.001]) and associated with the occurrence of at least one acute
exacerbation (OR 14.44; p < 0.001) during the same interval. The above factors
remained significant when repeating the analysis for hospitalisation based on
change in FVC%pred or events occurring during the previous 3 months interval.
Smoker status and a unit change in FVC%pred during the previous interval were
added to the significant factors. Physician visits during a 3-month interval were
significantly associated with a lower FVC%pred at the start of the interval (per
10-point decrement, OR 1.05; p = 0.040) and with the change in FVC%pred during
the same interval (per 10-point loss, OR 1.13; p = 0.042). Visits were also
associated with a 5-point drop in FVC%pred (OR 1.23; p = 0.020), age (per 5-year
increments OR 1.07; p = 0.028), and female sex (OR 1.32; p = 0.017).
Nevertheless, the predictive power of the models was considered poor for both
outcomes (hospitalisation and physician visits). CONCLUSIONS: Disease progression
and acute exacerbation events are significantly associated with hospitalisation
of patients with IPF. Outpatient visits to physicians are associated with disease
progression, baseline FVC%pred, age and sex.
PMID- 29943134
TI - Variation in airborne pollen concentrations among five monitoring locations in a
desert urban environment.
AB - The urbanization of the Las Vegas Valley has transformed this part of the Mohave
Desert into a green oasis by introducing many non-native plant species, some of
which are allergenic. Typically, one monitoring station is established per city
to obtain pollen counts for an entire metropolitan area. However, variations in
pollen concentrations could occur among different microenvironments. The
objective of this study is to measure and compare pollen concentrations in five
locations in Las Vegas to determine if there are significant differences between
microenvironments within the city. Air samples were collected from five sites
across the Las Vegas Valley over a 1-year period. Prepared slides were analyzed
with a light microscope for pollen grains and converted into airborne pollen
concentrations. Mixed model methods were used to determine mean differences. Tree
pollen was the greatest contributor to the annual average airborne pollen
concentrations (130 grains/m3) compared to weeds (6 grains/m3) and grass (3
grains/m3). The highest peak occurred in March 2016 (9589 total grains/m3). There
were several differences among sites with respect to concentrations of individual
tree species and for total weed and grass concentrations. We observed significant
variations in concentration and composition among the five pollen collection
stations that were established across the Las Vegas Valley. This study presented
new outdoor pollen data for the southwest region of the USA, focused in Las
Vegas. The results indicate that more sites and comprehensive monitoring of
outdoor allergens are needed to provide accurate information to the community
about outdoor air quality conditions.
PMID- 29943135
TI - Use of Epidural Analgesia in Sigmoidectomy: Is There Any Advantage in the Era of
Minimally Invasive Surgery?
AB - BACKGROUND: There is no consensus as to the effects of epidural analgesia on
postoperative outcomes after laparoscopy in the context of the Enhanced Recovery
Programs. The aim of this study was to evaluate the effects of epidural analgesia
on postoperative outcomes after elective laparoscopic sigmoidectomy. METHODS: The
use of epidural analgesia was discontinued in elective laparoscopic sigmoidectomy
and substituted by the perioperative administration of systemic lidocaine. Data
from patients undergoing elective laparoscopic sigmoidectomy between January 2014
and September 2016 was prospectively analysed. Patients with epidural analgesia
were compared with patients without, in analgesics administrated postoperatively,
length of stay, day of first defecation and mobilisation, and complication and
reoperation rates. RESULTS: A total of 160 patients (male 85; female 75), median
age 68 (30-92 years), were included. The groups consisted of 80 patients each.
Mean length of stay (5.6 vs. 7.2 days, p = 0.03) and day of first mobilisation
(mean 1.2 vs. 1.6 days, p = 0.004) were significantly shorter in the group
without epidural analgesia. Reoperation rate (7.5 vs. 2.5%) was not statistically
different. Complication rate was significantly lower (12.5 vs. 30%, p = 0.007) in
the group without epidural. Day of first defecation was shorter in the epidural
group (1.4 vs. 1.7 days, p = 0.04). Mean amount of analgesics administrated was
not statistically different between groups, except for metamizole, that was
administrated more in the group without epidural. CONCLUSIONS: Epidural analgesia
did not offer benefits on postoperative analgesia or outcomes after elective
laparoscopic sigmoidectomy, causing longer length of stay, later mobilisation and
higher complication rate.
PMID- 29943136
TI - Independent Predictors of Increased Operative Time and Hospital Length of Stay
Are Consistent Across Different Surgical Approaches to Pancreatoduodenectomy.
AB - BACKGROUND: While minimally invasive approaches are increasingly being utilized
for pancreatoduodenectomy (PD), factors associated with prolonged operative time
(OpTime) and hospital length of stay (LOS) remain poorly defined, and it is
unclear whether these factors are consistent across surgical approaches. METHODS:
The ACS-NSQIP targeted pancreatectomy database from 2014 to 2016 was used to
identify all patients who underwent open (OPD), laparoscopic (LPD), or robotic
(RPD) pancreatoduodenectomy. Multivariable linear regression analyses were used
to evaluate predictors of OpTime and LOS, as well as quantify the changes
observed relative to each surgical approach. RESULTS: Among 10,970 patients, PD
procedure types varied: 9963 (92%) open, 418 (4%) laparoscopic, and 409 (4%)
robotic. LOS was longer for the open and laparoscopic approaches (11 vs. 11 vs.
10 days, P = 0.0068), whereas OpTime was shortest for OPD (366 vs. 426 vs. 435
min, P < 0.0001). Independent predictors of a prolonged OpTime were ASA class >=
3 (P = 0.0002), preoperative XRT (P < 0.0001), pancreatic duct < 3 mm (P =
0.0001), T stage >= 3 (P = 0.0108), and vascular resection (P < 0.0001) for OPD;
T stage >= 3 (P = 0.0510) and vascular resection (P = 0.0062) for LPD; and
malignancy (P = 0.0460) and conversion to laparotomy (P = 0.0001) for RPD.
Independent predictors of increased LOS were age >= 65 years (P = 0.0002), ASA
class >= 3 (P = 0.0012), hypoalbuminemia (P < 0.0001), and preoperative blood
transfusion (P < 0.0001) for OPD as well as an OpTime > 370 min (all p < 0.05)
and specific postoperative complications (all p < 0.05) for all surgical
approaches. CONCLUSIONS: Perioperative risk factors for prolonged OpTime and
hospital LOS are relatively consistent across open, laparoscopic, and robotic
approaches to PD. Particular attention to these factors may help identify
opportunities to improve perioperative quality, enhance patient satisfaction, and
ensure an efficient allocation of hospital resources.
PMID- 29943137
TI - Should Surgical Treatment Be Provided to Patients with Colorectal Cancer Who Are
Aged 90 Years or Older?
AB - PURPOSE: The number of patients aged >= 90 years is increasing worldwide;
however, the treatment guidelines for colorectal cancer in elderly patients
remain unclear. This study aimed to investigate the clinical outcomes of patients
with primary colorectal cancer aged >= 90 years. METHODS: We retrospectively
reviewed the medical records of 100 patients (aged >= 90 years) with primary
colorectal adenocarcinoma. Their demographic and clinical characteristics and
surgical outcomes were assessed. RESULTS: The patients who underwent tumor
resections (n = 71) showed longer overall and cancer-specific survival than those
who underwent non-operative treatments (n = 29) (median overall survival time:
23.92 months vs. 2.99 months, P < 0.0001). Age, body mass index, performance
status, advanced cancer stage (stages 3 and 4), and treatment strategy were
identified as risk factors, prognostic factors, and predictors of overall
survival. No significant differences in the postoperative morbidity rate, in
hospital mortality rate, and survival time were found between the elective
laparoscopic (n = 27) and elective open (n = 37) surgery subgroups. However, the
in-hospital mortality rate was 6.25% (4/64) in the patients who underwent
elective open surgeries and 42.9% (3/7) in those who underwent emergent open
surgeries (p = 0.0179). CONCLUSIONS: In clinical practice, surgical treatment
should not be denied to patients with primary colorectal cancer aged >= 90 years.
However, the high complication and mortality rates for emergency surgeries act as
a deterrent. Further studies to eliminate the bias between operative and non
operative groups may be needed to validate our results.
PMID- 29943138
TI - Acquired Adult Aerodigestive Fistula: Classification and Management.
AB - BACKGROUND: Acquired aerodigestive fistulae (ADF) are rare, but associated with a
high mortality rate. We present our experience of the diagnosis, management and
outcomes of patients with ADFs treated at a tertiary centre. Utilising our
findings, we propose an anatomical classification system, demonstrating how
specific features of an ADF may determine management. METHODS: A clinical
database was searched and 48 patients with an ADF were identified. A
classification system was developed based on anatomical location of the ADF and
differences in clinico-pathological features based on this categorisation were
performed, with the chi-squared test used for inferential analyses and Kaplan
Meier curves with log-rank test to assess survival. RESULTS: Twenty (41.6%)
patients developed an ADF secondary to malignancy, with previous radiotherapy
(18.7%), post-operative anastomotic dehiscence and endotherapy (14.6% each)
representing other causes. Thirty-one patients were managed with tracheal and/or
oesophageal stents and eight underwent surgical repair. The classification system
demonstrated benign causes of ADF were either proximally or distally sited,
whilst a malignant cause resulted in mid-tracheal fistulae (p = 0.001), with the
latter associated with poorer survival. ADFs over 20 mm in size were associated
with poor survival (p = 0.011), as was the use of previous radiotherapy. Proximal
and distal ADFs were associated with improved survival (p = 0.006), as were those
patients managed surgically (p = 0.001). CONCLUSION: By classifying ADFs, we have
demonstrated that anatomical location correlates with the size, history of
malignancy, previous radiotherapy and aetiology of ADF, which can affect
management. The proposed classification system will aid in formulating multi
modality individualised treatment plans.
PMID- 29943140
TI - Laparoscopic Heller Myotomy and Hiatal Hernia Repair After Failed Peroral
Endoscopic Myotomy.
PMID- 29943139
TI - Sarcopenic Obesity Is Associated with Severe Postoperative Complications in
Gastric Cancer Patients Undergoing Gastrectomy: a Prospective Study.
AB - OBJECTIVE: This study aimed to determine the risk of severe postoperative
complications (SPCs) in patients with gastric cancer and to construct a nomogram
based on independently related factors to identify high-risk patients. METHODS:
We conducted a prospective study of 636 consecutive patients with gastric cancer
who underwent radical gastrectomy. Degrees of sarcopenia and obesity were
calculated before surgery. Factors contributing to SPCs were determined using
univariate and multivariate analysis. A nomogram consisting of the independent
risk factors was constructed to quantify the individual risk of SPCs. RESULTS:
Logistic analysis revealed that sarcopenic obesity, age, open surgery, and
combined resection were independent prognostic factors for SPCs. Sarcopenic obese
patients have the highest risk in all patients (sarcopenic obesity vs normal, OR
= 6.575 p = 0.001; sarcopenic obesity vs obesity, OR = 5.833 p = 0.001;
sarcopenic obesity vs sarcopenia, OR = 2.571 p = 0.032), while obese patients
share the similar rate of SPCs with normal people (obesity vs normal, OR = 1.056
p = 0.723). The nomogram we constructed was able to quantify the risk of SPCs
reliably (c-index, 0.737). CONCLUSIONS: Sarcopenic obesity, together with age,
open surgery, and combined resection are independent predictors of SPCs. Obesity
will significantly increase the risk of SPCs in sarcopenic patient with gastric
cancer, but it will not bring higher risk to normal patients. Our nomogram is a
simple and practical instrument to identify patients at high risk of surgical
complications.
PMID- 29943141
TI - IDH wild-type WHO grade II diffuse low-grade gliomas. A heterogeneous family with
different outcomes. Systematic review and meta-analysis.
AB - WHO grade II diffuse low-grade gliomas (DLGGs) were recently divided into sub
groups on the basis of their molecular profiles. IDH wild-type (IDH-wt) tumors
seem to be associated with unfavorable prognoses due to biological similarities
to glioblastomas. The authors performed a systematic review and meta-analysis of
literature examining epidemiology, clinical characteristics, management, and the
outcome of IDH-wt grade II DLGGs. According to PRISMA guidelines, a comprehensive
review of studies published from January 2009 to October 2017 was carried out.
The authors identified series that examined the prevalence rate, clinical and
radiological characteristics, treatment, and outcome of IDH-wt DLGGs. Variables
influencing outcomes were analyzed using a random-effects meta-analysis model.
Finally, a meta-regression analysis was performed to examine the impact of
therapeutic strategies on the effect-size. Twenty-two studies were included in
this systematic review. The IDH-wt prevalence rate was 22.9% (95% CI 18.4-27.4%).
The hazard ratio for this molecular subgroup in the DLGGs population was 3.46
(95% CI 2.24-5.36; p < 0.001), and the heterogeneity was significant (I2 = 85%,
tau2 = 0.88) (HR range 1.28-376). Nonetheless, publication bias did not affect
the analysis (p = 0.176). The meta-regression revealed that the extent of
resection and post-operative chemotherapy affected the outcome in the IDH-wt
subgroup (p < 0.001 and 0.015, respectively), with no significant association of
the HR with the rate of RT or RT + CHT. The prevalence of IDH-wt tumors is
approximately 23% of DLGGs. The absence of IDH mutation is associated with a
heterogeneous outcome, and its therapeutic relevance for postoperative management
remains unclear. Maximal surgical resection improves the overall survival in the
DLGGs population, beyond molecular status. Further molecular stratification is
needed to better understand IDH-wt behavior and therapeutic response.
PMID- 29943142
TI - 18F-sodium fluoride positron emission tomography assessed microcalcifications in
culprit and non-culprit human carotid plaques.
AB - BACKGROUND: 18F-NaF positron emission tomography (PET) targets
microcalcifications. We compared in vitro microPET assessed 18F-NaF uptake
between culprit and non-culprit human carotid plaques. Furthermore, we compared
18F-NaF uptake with calcification visualized on microcomputed tomography
(microCT). METHODS: Carotid plaques from stroke patients undergoing surgery were
incubated in 18F-NaF and scanned using a microPET and a microCT scan. The average
PET assessed 18F-NaF uptake was expressed as percentage of the incubation dose
per gram (%Inc/g). 18F-NaF PET volume of interest (VOI) was compared with CT
calcification VOI. RESULTS: 23 carotid plaques (17 culprit, 6 non-culprit) were
included. The average 18F-NaF uptake in culprit carotid plaques was comparable
with the uptake in non-culprit carotid plaques (median 2.32 %Inc/g [IQR 1.98 to
2.81] vs. median 2.35 %Inc/g [IQR 1.77 to 3.00], P = 0.916). Only a median of 10%
(IQR 4 to 25) of CT calcification VOI showed increased 18F-NaF uptake, while
merely a median of 35% (IQR 6 to 42) of 18F-NaF PET VOI showed calcification on
CT. CONCLUSIONS: 18F-NaF PET represents a different stage in the calcification
process than CT. We observed a similar PET assessed 18F-NaF uptake and pattern in
culprit and non-culprit plaques of high-risk patients, indicating that this
method may be of more value in early atherosclerotic stenosis development.
PMID- 29943143
TI - Genetic variation in mutualistic and antagonistic interactions in an invasive
legume.
AB - Mutualists may play an important role in invasion success. The ability to take
advantage of novel mutualists or survive and reproduce despite a lack of
mutualists may facilitate invasion by those individuals with such traits. Here,
we used two greenhouse studies to examine how soil microbial communities in
general and mutualistic rhizobia in particular affect the performance of a legume
species (Medicago polymorpha) that has invaded five continents. We performed two
plant growth experiments with Medicago polymorpha, inoculating them with soil
slurries in one experiment or rhizobial cultures in another experiment. For both
experiments, we compared the growth of Medicago in competition with conspecific
or heterospecific plants and examined variation among plant genotypes collected
from the native and introduced ranges. We found that all genotypes experienced
similar increases in biomass and formed more nodules that house rhizobia bacteria
when inoculated with soil from a previously invaded site, compared to
uninoculated plants or plants inoculated with soil from uninvaded and low
invasion sites. In a second experiment, plants inoculated with rhizobia generally
produced more biomass, had greater tolerance to interspecific competition, and
had greater effects on competitor biomass than uninoculated plants. However,
plant genotypes collected from the native range benefited more from rhizobia and
were less tolerant of competition relative to genotypes collected from the
introduced range. In the introduced range, compatible mutualists may not be
readily available but competition is intense, causing Medicago to evolve to
benefit less from interactions with rhizobia mutualists, while simultaneously
becoming more tolerant of competition.
PMID- 29943144
TI - Reduced dry season transpiration is coupled with shallow soil water use in
tropical montane forest trees.
AB - Tropical montane cloud forests (TMCF) are ecosystems particularly sensitive to
climate change; however, the effects of warmer and drier conditions on TMCF
ecohydrology remain poorly understood. To investigate functional responses of
TMCF trees to reduced water availability, we conducted a study during the 2014
dry season in the lower altitudinal limit of TMCF in central Veracruz, Mexico.
Temporal variations of transpiration, depth of water uptake and tree water
sources were examined for three dominant, brevi-deciduous species using
micrometeorological, sap flow and soil moisture measurements, in combination with
oxygen and hydrogen stable isotope composition of rainfall, tree xylem, soil and
stream water. Over the course of the dry season, reductions in crown conductance
and transpiration were observed in canopy species (43 and 34%, respectively) and
mid-story trees (23 and 8%), as atmospheric demand increased and soil moisture
decreased. Canopy species consistently showed more depleted isotope values
compared to mid-story trees. However, MixSIAR Bayesian model results showed that
the evaporated (enriched) soil water pool was the main source for trees despite
reduced soil moisture. Additionally, while increases in tree water uptake from
deeper to shallower soil water sources occurred, concomitant decreases in
transpiration were observed as the dry season progressed. A larger reduction in
deep soil water use was observed for canopy species (from 79 +/- 19 to 24 +/-
20%) compared to mid-story trees (from 12 +/- 17 to 10 +/- 12%). The increase in
shallower soil water sources may reflect a trade-off between water and nutrient
requirements in this forest.
PMID- 29943145
TI - Aliens will provide: avian responses to a new temporal resource offered by
ornithocorous exotic shrubs.
AB - Frugivorous birds are able to track spatiotemporal changes in fruit availability.
Food resource fluctuations, characteristic of seasonal environments, can be
affected by the naturalization of exotic ornithocorous plants. In the mountain
forest of central Argentina, invasive shrubs of the genus Pyracantha provide a
new temporal resource that modifies fluctuations of natural resource availability
because the invasives fructify in autumn-winter (largely uncoupled with the
fruiting of native species). The contrasting patterns of resource fluctuation
between non-invaded and invaded areas throughout the year provide a good study
system to test predictions of the fruit-tracking hypothesis, and to understand
the relationship between food resources offered by fleshy fruited invasives and
abundances of avian trophic guilds. By means of point counts conducted during
five time periods at invaded and non-invaded sites we found that the presence of
Pyracantha, and time periods, significantly affected frugivorous bird abundance,
which in autumn-winter was greater in invaded sites and in spring-summer similar
between invaded and non-invaded sites. On the other hand, granivores and
insectivores did not show a significant relationship with the presence of
Pyracantha. Abundances of the most common seed disperser were significantly
affected by the interaction between time period and presence of Pyracantha. These
results indicate that the abundances of birds that legitimately disperse
Pyracantha seeds are temporally and spatially associated with fruit abundance
provided by this exotic plant. This underscores fruit availability as an
important ecological factor affecting frugivorous bird abundance, and suggests
that Pyracantha seed dispersers are capable of detecting changes in the
availability of its fruit, likely contributing to the effectiveness of its
dispersal.
PMID- 29943146
TI - Upper cervical two-point discrimination thresholds in migraine patients and
headache-free controls.
AB - BACKGROUND: Chronic pain including migraine is associated with structural and
functional changes in the somatosensory cortex. Previous reports proposed two
point discrimination (TPD) as a measurement for cortical alterations. Limited
evidence exists for tactile acuity in the neck and no data is available for
migraine. METHODS: To introduce a standardized protocol for the measurement of
TPD in the upper cervical spine, 51 healthy participants were investigated with a
newly developed paradigm which was evaluated for intra-rater reliability. The
same protocol was applied by two further examiners to 28 migraine patients and 21
age-, and gender-matched healthy controls to investigate inter-rater reliability
and between group differences. RESULTS: Results indicated excellent intra-rater
(right ICC(2,4) = 0.82, left ICC(2,4) = 0.83) and good inter-rater reliability
(right ICC(2,4) = 0.70, left ICC(2,4) = 0.75). Migraine patients had larger TPD
thresholds (26.86 +/- 7.21) than healthy controls (23.30 +/- 6.17) but these
became only statistically significant for the right side of the neck (p = 0.02).
There was a significant, moderate association with age for the right side (r =
0.42 p = 0.002, n = 51), and less strong association for the left side (r = 0.34,
p = 0.14) in healthy individuals. TPD did not correlate with headache days per
month or the dominant headache side in migraine patients. CONCLUSIONS:
Surprisingly, migraine patients showed increased TPD thresholds in the upper
cervical spine interictally. Although a body of evidence supports that
hypersensitivity is part of the migraine attack, the current report indicates
that interictally, migraine patients showed worse tactile acuity similar to other
chronic pain populations. This has been hypothesized to indicate structural and
functional re-organisation of the somatosensory cortex.
PMID- 29943147
TI - Effect of Temporal Expression of Integral Membrane Proteins by Baculovirus
Expression Vector System.
AB - Integral membrane proteins (IMPs) are popular target for drugs, but their
resolved structures have been overlooked when compared with cytosolic proteins.
The main reason is that IMPs usually need intensive post-translational
modifications and they are bound to membranes, which increase the complexity of
purifying or crystalizing them. Although different expression systems are used to
express IMPs, baculovirus is considered one of the most successful expression
systems for those proteins. Despite that, there are always unknown discrepancies
in the level of IMPs expression in the baculovirus expression system.
Retrospective studies have shown that expression of an immunoglobulin (anti
Chymase mouse monoclonal IgG1) driven by vp39 promoter was more efficient
compared to its expression under polyhedrin (polh) promoter; however, this
conclusion was not tested on different IMPs to generalize such a conclusion. In
this study, the expression of eight different IMPs has been compared under vp39
and polh promoters of Autographa californica nucleopolyhedrovirus. Although
different IMPs have shown different patterns of expression, the expression driven
by vp39 promoter was found to be generally more efficient than the polh promoter.
PMID- 29943148
TI - Engineering Yarrowia lipolytica for Use in Biotechnological Applications: A
Review of Major Achievements and Recent Innovations.
AB - Yarrowia lipolytica is an oleaginous saccharomycetous yeast with a long history
of industrial use. It aroused interest several decades ago as host for
heterologous protein production. Thanks to the development of numerous molecular
and genetic tools, Y. lipolytica is now a recognized system for expressing
heterologous genes and secreting the corresponding proteins of interest. As
genomic and transcriptomic tools increased our basic knowledge on this yeast, we
can now envision engineering its metabolic pathways for use as whole-cell factory
in various bioconversion processes. Y. lipolytica is currently being developed as
a workhorse for biotechnology, notably for single-cell oil production and
upgrading of industrial wastes into valuable products. As it becomes more and
more difficult to keep up with an ever-increasing literature on Y. lipolytica
engineering technology, this article aims to provide basic and actualized
knowledge on this research area. The most useful reviews on Y. lipolytica
biology, use, and safety will be evoked, together with a resume of the
engineering tools available in this yeast. This mini-review will then focus on
recently developed tools and engineering strategies, with a particular emphasis
on promoter tuning, metabolic pathways assembly, and genome editing technologies.
PMID- 29943150
TI - Soluble Production of Human Recombinant VEGF-A121 by Using SUMO Fusion Technology
in Escherichia coli.
AB - Human recombinant vascular endothelial growth factor-A121 (hrVEGF-A121) has
applications in pharmaceutical industry especially in regenerative medicine.
Here, we report the expression, purification, and characterization of hrVEGF-A121
in Escherichia coli expression system using human small ubiquitin-related
modifier-3 (hSUMO3) fusion partner. Total RNA was isolated from healthy human
gingival tissue, VEGF-A121 gene was RT-PCR amplified, and hSUMO3 gene was tagged
at N-terminus. The fusion gene (SUMO3-VEGF-A121) was cloned in pET-22b(+)
expression vector and transferred into E. coli strains; BL21 codon + and Rosetta
gami B(DE3). The hrVEGF-A121 expression was optimized for temperature, IPTG
concentration, and time in Terrific Broth (TB). The positive transformants were
sequenced and hrVEGF-A121 nucleotide sequence was submitted to Genbank (Accession
No. KT581010). Approximately 40% of total cell protein expression was observed in
soluble form on 15% SDS-PAGE. The hSUMO3 was cleaved from hrVEGF-A121 with SUMO
protease and purified by Fast Protein Liquid Chromatography using anionic Hi-trap
Resource Q column. From 100 ml TB, ~ 25.5% and ~ 6.8 mg of hrVEGF-A121 protein
was recovered. The dimerized hrVEGF-A121 was characterized by Native PAGE and
Western blot, using human anti-VEGF-A antibody and ESI-MS showed dimeric hrVEGF
A121 at 31,015 Da. The biological activity of hrVEGF-A121 was assessed in vitro
by MTT and cell viability assay and observed to be bioactive.
PMID- 29943151
TI - Protective effect of isoliquiritigenin against cerebral injury in septic mice via
attenuation of NF-kappaB.
AB - BACKGROUND: The study was conducted to scrutinize the outcome of
isoliquiritigenin (ISL) against cerebral injury in septic mice. METHODS: The
sepsis was introduced using cecal ligation and puncture (CLP) method in
experimental mice. The effect of ISL was quantified using the content of brain
water and blood brain barrier (BBB) permeability. The effect on the levels of
myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA) and
glutathione (GSH) in brain homogenates was also determined. The effect of ISL on
the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6
in serum was also estimated. The levels of various inflammatory biomarkers (COX-2
and PGE2) were also studied. The expression of NF-kappaB signalling cascade and
inducible nitric oxide synthase (iNOS) was estimated by Western blot. RESULTS:
Compared with CLP group, the brain water content was found to be reduced
significantly together with the enhanced BBB integrity in ISL treated group. The
level of MDA was reduced together with enhanced level of SOD and GSH in the ISL
treated group. The levels of TNF-alpha, IL-1beta, and IL-6 were also found to be
modulated in ISL group. The level of COX-2 and PGE2 was reduced to near normal
after ISL administration together with increase in the IkappaBalpha expression
and reduction of p65 and p-p65 expression in a concentration-dependent manner.
The expression of iNOS was also found to be reduced in ISL group. CONCLUSION:
These results demonstrate that ISL causes protection of CLP-induced sepsis in
experimental mice via multiple pathways.
PMID- 29943149
TI - Combinatorial Interactions of Biotic and Abiotic Stresses in Plants and Their
Molecular Mechanisms: Systems Biology Approach.
AB - Plants are continually facing biotic and abiotic stresses, and hence, they need
to respond and adapt to survive. Plant response during multiple and combined
biotic and abiotic stresses is highly complex and varied than the individual
stress. These stresses resulted alteration of plant behavior through regulating
the levels of microRNA, heat shock proteins, epigenetic variations. These
variations can cause many adverse effects on the growth and development of the
plant. Further, in natural conditions, several abiotic stresses causing factors
make the plant more susceptible to pathogens infections and vice-versa. A very
intricate and multifaceted interactions of various biomolecules are involved in
metabolic pathways that can direct towards a cross-tolerance and improvement of
plant's defence system. Systems biology approach plays a significant role in the
investigation of these molecular interactions. The valuable information obtained
by systems biology will help to develop stress-resistant plant varieties against
multiple stresses. Thus, this review aims to decipher various multilevel
interactions at the molecular level under combinatorial biotic and abiotic
stresses and the role of systems biology to understand these molecular
interactions.
PMID- 29943152
TI - Incidence of nausea and vomiting in breast cancer patients treated with
anthracycline plus cyclophosphamide-based chemotherapy regimens in Italy: NAVY
observational study.
AB - PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse
event with cancer chemotherapy, despite the availability of effective antiemetic
agents. This is a prospective observational study of Italian breast cancer
patients treated with anthracycline plus cyclophosphamide (AC), assessed CINV
incidence, adherence to national antiemetic guidelines (AIOM 2012), and the
relationship with CINV outcomes. METHODS: Patients with breast cancer scheduled
to receive their first cycle of an AC-based regimen were enrolled at 12 Italian
centers and their clinical data prospectively recorded. CINV incidence was
assessed from patient diaries after the first chemotherapy cycle. The
relationship between guideline adherence and CINV outcomes was examined using
multiple logistic regression. RESULTS: The overall incidence rates of nausea and
vomiting among 246 evaluable patients were 63.0 and 25.4%, respectively. Most
patients received a 5-HT3-RA agent and dexamethasone for acute phase CINV
prophylaxis, whereas a triple combination including aprepitant (NK1-RA),
consistent with national guidelines, was used in only 45.5% of cases. In the
delayed phase, the guideline adherence was 48.8%, while the overall adherence was
43.5%. After adjusting for confounding factors, adherence to antiemetic
prophylaxis guidelines was associated with a significant reduction in the odds of
three endpoints, namely any nausea, "significant nausea," and vomiting (OR =
0.49, OR = 0.54, and OR = 0.48, respectively), and a 90% increase in the odds of
overall complete protection (OR = 1.90). CONCLUSIONS: CINV is still a critical
issue in AC-treated patients, despite antiemetic treatment. Non-adherence to
antiemetic guidelines may lead to poorer outcomes and indicates the need for
strategies to enhance the use of guidelines in clinical practice.
PMID- 29943153
TI - Is the relationship between social support and depressive symptoms mediated by
hope among Chinese central nervous system tumor patients?
AB - BACKGROUND: It is common for central nervous system (CNS) tumor patients to
suffer from depressive symptoms. If unrecognized or untreated, CNS tumors may
lead to many serious problems in these patients. This study examines the
association of social support with depressive symptoms in CNS tumor patients and
explores the extent to which hope mediates this relationship. METHODS: A total of
269 CNS tumor patients in China were included in this study. We assessed
depressive symptoms using the Epidemiologic Studies Depression Scale (CES-D),
social support using the Perceived Social Support Scale (PSSS), and hope using
the Herth Hope Index (HHI). Questionnaires were distributed to collect these
data. Hierarchical linear regression analyses explored the interrelationship
between social support, hope, and depressive symptoms. RESULTS: After adjustment
for demographic characteristics, patients with less social support exhibited more
depressive symptoms (beta = - 0.452, P < 0.01). Social support explained 19.1% of
the variance in depressive symptoms. After adding hope to the regression model,
the effect size for social support was reduced by over half but remained
significant (from beta = - 0.452 to beta = - 0.218, P < 0.01). In addition, a
lower level of hope (beta = - 0.386, P < 0.01) was associated with more
depressive symptoms, and this measure explained an additional 9.3% of the
variance in depressive symptoms. CONCLUSIONS: Much of the relationship between
social support and depressive symptoms is explained by hope. Thus, interventions
boosting both social support and hope help to reduce depressive symptoms in
patients with CNS tumors.
PMID- 29943154
TI - The Presence of HLA-A Bw4-80I KIR Ligands Could Predict "Difficult-to-Treat"
Psoriasis and Poor Response to Etanercept.
AB - BACKGROUND: Psoriasis is an immune-mediated dermatosis with a wide genetic
predisposition. The immunogenetic background, specifically interactions between
human leukocyte antigen (HLA) class I ligands and killer-cell immunoglobulin-like
receptor (KIRs), have functional significance in modulating natural killer (NK)
cells and can influence susceptibility and response to biological therapy.
OBJECTIVE: The main aim of this study was to correlate HLA-A and -B KIR ligands
with response to biological therapy in patients with psoriasis. METHODS: HLA-A
and -B polymorphisms were determined in 48 patients (35 males and 13 females),
with a mean of 22 years of disease (range 8-55). All patients were treated with
biological therapy (adalimumab, etanercept, infliximab, or ustekinumab) for at
least 6 months. RESULTS: This study identifies, with statistical significance,
the presence of at least one ligand HLA-A Bw4-80I in the "poor-responder"
population (patients who needed two or more biologics) compared with the
"responder" population (patients with good response after a single biological
drug) (47.62 vs. 11.11%; p = 0.006) as well as in "non-responders to etanercept"
compared with "responders to etanercept" (52.63 vs. 5%; p = 0.001). CONCLUSION:
Our preliminary results suggest that at least one ligand HLA-A Bw4-80I could be
associated with "difficult-to-treat" psoriasis and that this ligand may reduce
the probability of response to etanercept, producing more tumor necrosis factor
(TNF)-alpha and neutralizing NK activity through a predominance of activating
KIR. The ab initio identification of genetic markers of response to biologic
therapy could improve the efficacy and economic impact of these agents.
PMID- 29943155
TI - Angiogenesis and Hepatic Fibrosis: Western and Chinese Medicine Therapies on the
Road.
AB - Hepatic fibrosis is a common feature of almost all chronic liver diseases.
Formation of new vessels (angiogenesis) is a process strictly related to the
progressive fibrogenesis which leads to cirrhosis and liver cancer. This review
mainly concerns the relationship between angiogenesis and hepatic fibrosis, by
considering the mechanism of angiogenesis, cells in angiogenesis, anti-angiogenic
and Chinese medicine therapies.
PMID- 29943156
TI - A novel HIPEC technique using hybrid CO2 recirculation system: intra-abdominal
diffusion test in a porcine model.
AB - The role of loco-regional treatment of peritoneal carcinomatosis using
intraperitoneal chemotherapy is still investigated. Actually, new technologies
are suitable for these procedures, especially a new hybrid system using CO2
called Peritoneal Recirculation System (PRS-1.0 Combat). A HIPEC procedure in a
porcine model using the PRS system was conducted. The objective of
experimentation was to assess the distribution of liquid inside the abdomen, by
using methylene blue instead of chemotherapy. Moreover, we positioned six
different thermal probes in different abdominal regions inside the abdomen to
measure the temperature during procedure. During the procedure, all thermal
probes recorded an average temperature of 41.5 degrees . At the end of infusion,
the abdomen was emptied and then opened; the tracer distribution was recorded. No
technical problems were recorded during the procedure. Good distribution of
tracer was recorded. More studies are needed to investigate better this new
technology.
PMID- 29943157
TI - Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological
challenge.
AB - Treatment of malignant pleural mesothelioma (MPM) represents a highly unmet
medical need. Here, we discuss the results and therapeutic potential of first-
and second-generation immunomodulatory antibodies targeting distinct immune
checkpoints for the treatment of MPM, as well as their prospective therapeutic
role in combination strategies. We also discuss the role of appropriate
radiological criteria of response for MPM and the potential need of ad hoc
criteria of disease evaluation in MPM patients undergoing treatment with
immunotherapeutic agents.
PMID- 29943159
TI - Correction to: Real-world data on Len/Dex combination at second-line therapy of
multiple myeloma: treatment at biochemical relapse is a significant prognostic
factor for progression-free survival.
AB - The original version of this article contained a mistake. The name of Eirini
Katroditou should have been Eirini Katodritou. The original article has been
corrected.
PMID- 29943158
TI - Epigenetic responses to abiotic stresses during reproductive development in
cereals.
AB - KEY MESSAGE: Overview of current understanding of epigenetic alterations after
abiotic stresses during reproductive development in cereals. Abiotic stresses,
including heat, drought, cold, flooding, and salinity, negatively impact crop
productivity. Various stages during reproductive development are especially
sensitive to environmental stresses, which may lead to complete sterility and
severe yield losses. Plants exhibit diverse responses to ameliorate stress
damage. Changes in DNA methylation, histone modification as well as regulation of
small RNA and long noncoding RNA pathways have been shown to represent key
modulators in plant stress responses. During reproductive development in cereals,
various protein complexes controlling histone and DNA methylation have been
identified, revealing conserved and novel mechanisms regulating abiotic stress
responses in cereals and other plant species. New findings highlight the role of
transposable elements during stress periods. Here, we review our current
understanding of epigenetic stress responses during male and female gametophyte
formation (germline development), fertilization, early seed devolvement, and seed
maturation in cereals. An integrative model of epigenetic responses during
reproductive development in cereals is proposed, emphasizing the role of DNA
methylation and histone modifications during abiotic stresses.
PMID- 29943160
TI - Inferring potential small molecule-miRNA association based on triple layer
heterogeneous network.
AB - Recently, many biological experiments have indicated that microRNAs (miRNAs) are
a newly discovered small molecule (SM) drug targets that play an important role
in the development and progression of human complex diseases. More and more
computational models have been developed to identify potential associations
between SMs and target miRNAs, which would be a great help for disease therapy
and clinical applications for known drugs in the field of medical research. In
this study, we proposed a computational model of triple layer heterogeneous
network based small molecule-MiRNA association prediction (TLHNSMMA) to uncover
potential SM-miRNA associations by integrating integrated SM similarity,
integrated miRNA similarity, integrated disease similarity, experimentally
verified SM-miRNA associations and miRNA-disease associations into a
heterogeneous graph. To evaluate the performance of TLHNSMMA, we implemented
global and two types of local leave-one-out cross validation as well as fivefold
cross validation to compare TLHNSMMA with one previous classical computational
model (SMiR-NBI). As a result, for Dataset 1, TLHNSMMA obtained the AUCs of
0.9859, 0.9845, 0.7645 and 0.9851 +/- 0.0012, respectively; for Dataset 2, the
AUCs are in turn 0.8149, 0.8244, 0.6057 and 0.8168 +/- 0.0022. As the result of
case studies shown, among the top 10, 20 and 50 potential SM-related miRNAs,
there were 2, 7 and 14 SM-miRNA associations confirmed by experiments,
respectively. Therefore, TLHNSMMA could be effectively applied to the prediction
of SM-miRNA associations.
PMID- 29943162
TI - Epigenetics at the epicenter of a revolution in ARTs.
PMID- 29943161
TI - A semi-automatic technique to quantify complex tuberculous lung lesions on 18F
fluorodeoxyglucose positron emission tomography/computerised tomography images.
AB - BACKGROUND: There is a growing interest in the use of 18F-FDG PET-CT to monitor
tuberculosis (TB) treatment response. However, TB causes complex and widespread
pathology, which is challenging to segment and quantify in a reproducible manner.
To address this, we developed a technique to standardise uptake (Z-score),
segment and quantify tuberculous lung lesions on PET and CT concurrently, in
order to track changes over time. We used open source tools and created a MATLAB
script. The technique was optimised on a training set of five pulmonary
tuberculosis (PTB) cases after standard TB therapy and 15 control patients with
lesion-free lungs. RESULTS: We compared the proposed method to a fixed threshold
(SUV > 1) and manual segmentation by two readers and piloted the technique
successfully on scans of five control patients and five PTB cases (four cured and
one failed treatment case), at diagnosis and after 1 and 6 months of treatment.
There was a better correlation between the Z-score-based segmentation and manual
segmentation than SUV > 1 and manual segmentation in terms of overall spatial
overlap (measured in Dice similarity coefficient) and specificity (1 minus false
positive volume fraction). However, SUV > 1 segmentation appeared more sensitive.
Both the Z-score and SUV > 1 showed very low variability when measuring change
over time. In addition, total glycolytic activity, calculated using segmentation
by Z-score and lesion-to-background ratio, correlated well with traditional total
glycolytic activity calculations. The technique quantified various PET and CT
parameters, including the total glycolytic activity index, metabolic lesion
volume, lesion volumes at different CT densities and combined PET and CT
parameters. The quantified metrics showed a marked decrease in the cured cases,
with changes already apparent at month one, but remained largely unchanged in the
failed treatment case. CONCLUSIONS: Our technique is promising to segment and
quantify the lung scans of pulmonary tuberculosis patients in a semi-automatic
manner, appropriate for measuring treatment response. Further validation is
required in larger cohorts.
PMID- 29943163
TI - Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal
dissection-induced gastric ulcers: a prospective randomized phase II study.
AB - BACKGROUND: Vonoprazan, potassium-competitive acid blocker, is expected to reduce
incidence of delayed bleeding after gastric endoscopic submucosal dissection
(ESD); however, preliminary data to design a large-scale comparative study are
lacking. This study aimed to assess the efficacy of vonoprazan in preventing
delayed bleeding after gastric ESD. METHODS: In this single-center randomized
phase II trial, a modified screened selection design was used with a threshold
non-bleeding rate of 89% and an expected rate of 97%. In this design, Simon's
optimal two-stage design was first applied for each parallel group, and efficacy
was evaluated in comparison with the threshold rate using binomial testing.
Patients were randomly assigned in a 1:1 ratio to receive either vonoprazan 20 mg
(VPZ group) or lansoprazole 30 mg (PPI group) for 8 weeks from the day before
gastric ESD. The primary endpoint was the incidence of delayed bleeding, defined
as endoscopically confirmed bleeding accompanied by hematemesis, melena, or a
decrease in hemoglobin of >= 2 g/dl. RESULTS: Delayed bleeding occurred in three
of 69 patients (4.3%, 95% CI 0.9-12.2%, p = 0.047) in the VPZ group, and four of
70 (5.7%, 95% CI 1.6-14.0%, p = 0.104) in the PPI group. As only vonoprazan
showed significant reduction in delayed bleeding compared with the threshold
rate, it was determined to be efficacious treatment. CONCLUSIONS: Vonoprazan
efficaciously reduced the delayed bleeding rate in patients with an ESD-induced
gastric ulcer. A large-scale, randomized, phase III study is warranted to
definitively test the effectiveness of vonoprazan compared with proton pump
inhibitors.
PMID- 29943164
TI - Different mitochondrial response to cisplatin and hyperthermia treatment in human
AGS, Caco-2 and T3M4 cancer cell lines.
AB - Gastrointestinal cancers (gastric, pancreatic and colorectal) are life
threatening diseases, which easily spread to peritoneal cavity (Juhl et al. in
Int J Cancer 57:330-335, 1994; Schneider et al. in Gastroenterology 128:1606
1625, 2005; Geer and Brennan in Am J Surg 165:68-72 1993). Application of
hyperthermal intraperitoneal chemotherapy (HIPEC) is one of the choices treating
these malignancies and prolonging patient survival time. Despite numbers of
clinical trials showing positive effects of HIPEC against various types of
cancer, the question whether hyperthermia significantly potentiate the
cytotoxicity of cisplatin remains unanswered. Little information is available on
the HIPEC effect at the level of mitochondria. To define the effect of
hyperthermia (40 degrees C and 43 degrees C) to cisplatin treated human gastric
AGS, pancreatic T3M4 and colorectal Caco-2 cancer cells, we established an in
vitro experiment, which mimics clinical HIPEC conditions. Giving the importance
of mitochondrial energy metabolism in cancer, we investigated the effect of
cisplatin and hyperthermia on mitochondrial Complex-I (glutamate/malate) and
complex-II (succinate) dependent respiratory rates, the coupling of oxidative
phosphorylation, the proton permeability of mitochondrial inner membrane and on
the integrity of mitochondrial outer membrane in Caco-2, AGS and T3M4 cancer cell
lines. Our main findings are: 1) treatment of cells with cisplatin causes the
impairment of mitochondrial functions - the increase in the proton permeability
of mitochondrial inner membrane and decrease in the oxidative phosphorylation
efficiency in Caco-2, AGS and T3M4 cancer cells; 2) hyperthermia (40 degrees C
and 43 degrees C) increased state 2 respiration rate only in AGS cells without
any effects on Caco-2 and T3M4 cells; 3) hyperthermia in combination with
cisplatin doesn't enhance cisplatin effect neither in Caco-2 and T3M4 nor in AGS
cells. Thus, our results show the different mitochondrial response of gastric
AGS, pancreatic T3M4 and colorectal Caco-2 cancer cells to cisplatin or/and
hyperthermia - treatment. Further studies are needed to find the mechanisms of
cell line - specific mitochondrial response to cisplatin and hyperthermia.
PMID- 29943165
TI - Noninvasive auto-titrating ventilation (AVAPS-AE) versus average volume-assured
pressure support (AVAPS) ventilation in hypercapnic respiratory failure patients:
reply.
PMID- 29943166
TI - Penile self-amputation.
PMID- 29943167
TI - Linalool, citral, eugenol and thymol: control of planktonic and sessile cells of
Shigella flexneri.
AB - The antimicrobial activity of linalool, citral, eugenol and thymol was determined
in growth studies of both planktonic (PC) and biofilm cells (BC) Shigella
flexneri. These components were evaluated either in isolation or in combinations
using a sequential experimental strategy with Plackett & Burman and central
composite rotational designs totaling 47 treatments. The minimum inhibitory
concentration for PC was 0.125% (v v-1) for linalool and 0.5% (v v-1) for citral,
eugenol and thymol. The biofilm minimum bactericidal concentration was 3 and 1%
(v v-1) for linalool and citral, respectively, and 2% (v v-1) for eugenol and
thymol. In the mixtures, the minimum concentrations in the efficient assays for
PC growth inhibition were 0.0003, 0.0443 and 0.0443% (v v-1), for linalool,
citral and thymol, respectively. In the BC, only two assays with concentrations
of 0.0558, 0.0558 and 0.319% (v v-1) and 0.035, 0.035 and 0.3999% (v v-1) for
linalool, citral and thymol, respectively, inhibited Shigella growth. Synergism
was observed among the components, where PC and BC growth inhibition occurred at
lower concentrations than those noted individually. The bactericidal effect of
the components in microplate was different from the observed in stain steel
coupons. Therefore, the obtained model can describe and predict the PC count of
S. flexneri in medium with the tested compounds and they could be an alternative
for the use in microbiological control in food industry.
PMID- 29943168
TI - Thoracoscopic right middle lobe segmentectomy.
AB - Reports of right middle lobe segmentectomy are rare. We report here that
anatomical right middle lobe segmentectomy is a relatively simple surgical
procedure and can achieve good expansion of the remnant lung for patients with a
relatively large right middle lobe.
PMID- 29943169
TI - Two different methods to assess sympathetic tone during general anesthesia lead
to different findings.
AB - Noxious stimulation influences the autonomic nervous system activity. Sympathetic
tone monitoring is currently used to assess the adequacy of the balance between
nociception and anti-nociception during general anesthesia. The Surgical
Plethysmographic Index (SPI) and the EBMi software (Custos(c)) are commercial
devices that use different algorithms to measure it. We aimed at determining
whether those devices provide similar information during routine surgical
procedures under general anesthesia. Data acquired during a previously published
study in patients undergoing surgery under general anesthesia were
retrospectively analyzed and passed through the EBMi software. The occurrence of
EBMi alarms of increased sympathetic tone was compared to the occurrence of SPI
values >= 60, a commonly recommended intraoperative SPI threshold. Trends in
classical parameters of sympathetic tone during the 5 min preceding a SPI >= 60,
namely blood pressure, heart rate, and plethysmographic pulse amplitude were
assessed. SPI >= 60 episodes (n = 307) were more frequent than EBMi alerts (n =
240). Approximately 70% of EBMi alerts occurred during periods where the SPI was
below 60. Among all episodes of SPI >= 60, absence of any EBMi alerts was much
more frequent than the inverse. A majority, but not all SPI >= 60 episodes were
consistently preceded by an increase in heart rate and/or a decrease in pulse
amplitude. Blood pressure did not significantly change before SPI >= 60. Longer
SPI >= 60 episodes were associated with lower anti-nociception anesthetic
regimen. Different methods of sympathetic tone assessment during general
anesthesia provide conflicting information. Prospective studies should be
undertaken to clarify the clinical indications of both techniques.
PMID- 29943170
TI - Insurance, chronic health conditions, and utilization of primary and specialty
outpatient services: a Childhood Cancer Survivor Study report.
AB - PURPOSE: Survivors of childhood cancer require life-long outpatient healthcare,
which may be impacted by health insurance. This study sought to understand
survivors' utilization of outpatient healthcare provider services. METHODS: The
study examined cross-sectional survey data using an age-stratified sample from
the Childhood Cancer Survivor Study of self-reported annual use of outpatient
services. Multivariable logistic regression analyses were used to identify risk
factors associated with utilization of services. RESULTS: Six hundred ninety
eight survivors were surveyed, median age 36.3 years (range 22.2-62.6), median
time from diagnosis 28.8 years (range 23.1-41.7). Almost all (93%) of survivors
had at least one outpatient visit during the previous year; 81.3% of these visits
were with a primary care providers (PCP), 54.5% were with specialty care
physicians, 30.3% were with nurse practitioner/physician's assistants (NP/PA),
and 14.2% were with survivorship clinic providers. Survivors with severe to life
threatening chronic health conditions had greater odds of utilizing a specialty
care physician (OR = 5.15, 95% CI 2.89-9.17) or a survivorship clinic (OR = 2.93,
95% CI 1.18-7.26) than those with no chronic health conditions. Having health
insurance increased the likelihood of seeking care from NP/PA (private, OR =
2.76, 95% CI 1.37-5.58; public, OR = 2.09, 95% CI 0.85-5.11), PCP (private, OR =
7.82, 95% CI 3.80-13.10; public, OR = 7.24, 95% CI 2.75-19.05), and specialty
care (private, OR = 2.96, 95% CI 1.48-5.94; public, OR = 2.93, 95% CI 1.26-6.84)
compared to without insurance. CONCLUSION: Most childhood cancer survivors
received outpatient care from a PCP, but a minority received care from a
survivorship clinic provider. Having health insurance increased the likelihood of
outpatient care. IMPLICATIONS FOR CANCER SURVIVORS: Targeted interventions in the
primary care setting may improve risk-based, survivor-focused care for this
vulnerable population.
PMID- 29943171
TI - Flexible voices: Identity perception from variable vocal signals.
AB - Human voices are extremely variable: The same person can sound very different
depending on whether they are speaking, laughing, shouting or whispering. In
order to successfully recognise someone from their voice, a listener needs to be
able to generalize across these different vocal signals ('telling people
together'). However, in most studies of voice-identity processing to date, the
substantial within-person variability has been eliminated through the use of
highly controlled stimuli, thus focussing on how we tell people apart. We argue
that this obscures our understanding of voice-identity processing by controlling
away an essential feature of vocal stimuli that may include diagnostic
information. In this paper, we propose that we need to extend the focus of voice
identity research to account for both "telling people together" as well as
"telling people apart." That is, we must account for whether, and to what extent,
listeners can overcome within-person variability to obtain a stable percept of
person identity from vocal cues. To do this, our theoretical and methodological
frameworks need to be adjusted to explicitly include the study of within-person
variability.
PMID- 29943172
TI - Characterizing belief bias in syllogistic reasoning: A hierarchical Bayesian meta
analysis of ROC data.
AB - The belief-bias effect is one of the most-studied biases in reasoning. A recent
study of the phenomenon using the signal detection theory (SDT) model called into
question all theoretical accounts of belief bias by demonstrating that belief
based differences in the ability to discriminate between valid and invalid
syllogisms may be an artifact stemming from the use of inappropriate linear
measurement models such as analysis of variance (Dube et al., Psychological
Review, 117(3), 831-863, 2010). The discrepancy between Dube et al.'s,
Psychological Review, 117(3), 831-863 (2010) results and the previous three
decades of work, together with former's methodological criticisms suggests the
need to revisit earlier results, this time collecting confidence-rating
responses. Using a hierarchical Bayesian meta-analysis, we reanalyzed a corpus of
22 confidence-rating studies (N = 993). The results indicated that extensive
replications using confidence-rating data are unnecessary as the observed
receiver operating characteristic functions are not systematically asymmetric.
These results were subsequently corroborated by a novel experimental design based
on SDT's generalized area theorem. Although the meta-analysis confirms that
believability does not influence discriminability unconditionally, it also
confirmed previous results that factors such as individual differences mediate
the effect. The main point is that data from previous and future studies can be
safely analyzed using appropriate hierarchical methods that do not require
confidence ratings. More generally, our results set a new standard for analyzing
data and evaluating theories in reasoning. Important methodological and
theoretical considerations for future work on belief bias and related domains are
discussed.
PMID- 29943173
TI - The relationship between responsiveness to social and monetary rewards and ADHD
symptoms.
AB - Alterations in reward processing are frequently reported in attention deficit
hyperactivity disorder (ADHD). One important factor affecting reward processing
is the quality of reward as social and monetary rewards are processed by
different neural networks. However, the effect of reward type on reward
processing in ADHD has not been extensively studied. Hence, in the current study,
an exploratory research was conducted to investigate the effect of reward type
(i.e., social or monetary) on different phases of reward processing. We recorded
event-related potentials (ERPs) during a spatial attention paradigm in which cues
heralded availability and type of the upcoming reward and feedbacks informed
about the reward earned. Thirty-nine (19 males) healthy individuals (age range:
19-27 years) participated in the study. ADHD symptoms were assessed by using ADHD
self-report scale (ASRS). Our results revealed a consistent negative correlation
between the hyperactivity subscale of ASRS and almost all social-feedback related
ERPs (P2, P3, and FRN). ERP amplitudes after social feedbacks were less positive
for P2 and P3 and more negative for FRN for individuals with greater
hyperactivity levels. Our findings suggest that hyporesponsiveness to social
feedbacks may be associated with hyperactivity. However, the results have to be
confirmed with clinical populations.
PMID- 29943174
TI - Adolescents' neural response to social reward and real-world emotional closeness
and positive affect.
AB - Feeling emotionally close to others during social interactions is a ubiquitous
and meaningful experience that can elicit positive affect. The present study
integrates functional magnetic resonance imaging (fMRI) and ecological momentary
assessment (EMA) to investigate whether neural response to social reward (1) is
related to the experience of emotional closeness and (2) moderates the
association between emotional closeness and positive affect during and following
social interactions. In this study, 34 typically developing adolescents (ages 14
18 years) completed a social-reward fMRI task, a monetary-reward fMRI task, and a
2-week EMA protocol regarding their social and affective experiences. Adolescents
with greater right posterior superior temporal sulcus/temporoparietal junction
(pSTS/TPJ) response to social reward reported greater mean momentary emotional
closeness. Neural response to social reward in the right pSTS/TPJ moderated how
strongly momentary emotional closeness was associated with both concurrent
positive affect and future peak happiness, but in different ways. Although
emotional closeness had a significant positive association with concurrent
positive affect among adolescents at both high and low right pSTS/TPJ response
based on a follow-up simple slopes test, this association was stronger for
adolescents with low right pSTS/TPJ response. In contrast, emotional closeness
had a significant positive association with future peak happiness among
adolescents with high right pSTS/TPJ response, but not among those with low right
pSTS/TPJ response. These findings demonstrate the importance of neural response
to social reward in key social processing regions for everyday experiences of
emotional closeness and positive affect in the context of social interactions.
PMID- 29943175
TI - Cognitive changes in conjunctive rule-based category learning: An ERP approach.
AB - When learning rule-based categories, sufficient cognitive resources are needed to
test hypotheses, maintain the currently active rule in working memory, update
rules after feedback, and to select a new rule if necessary. Prior research has
demonstrated that conjunctive rules are more complex than unidimensional rules
and place greater demands on executive functions like working memory. In our
study, event-related potentials (ERPs) were recorded while participants performed
a conjunctive rule-based category learning task with trial-by-trial feedback. In
line with prior research, correct categorization responses resulted in a larger
stimulus-locked late positive complex compared to incorrect responses, possibly
indexing the updating of rule information in memory. Incorrect trials elicited a
pronounced feedback-locked P300 elicited which suggested a disconnect between
perception, and the rule-based strategy. We also examined the differential
processing of stimuli that were able to be correctly classified by the suboptimal
single-dimensional rule ("easy" stimuli) versus those that could only be
correctly classified by the optimal, conjunctive rule ("difficult" stimuli).
Among strong learners, a larger, late positive slow wave emerged for difficult
compared with easy stimuli, suggesting differential processing of category items
even though strong learners performed well on the conjunctive category set.
Overall, the findings suggest that ERP combined with computational modelling can
be used to better understand the cognitive processes involved in rule-based
category learning.
PMID- 29943176
TI - Neural evidence for the contribution of holistic processing but not attention
allocation to the other-race effect on face memory.
AB - Multiple mechanisms have been suggested to contribute to the other-race effect on
face memory, the phenomenon of better memory performance for own-race than other
race faces. Here, two of these mechanisms, increased attention allocation and
greater holistic processing during memory encoding for own-race than other-race
faces, were tested in two separate experiments. In these experiments event
related potentials were measured during study (the difference due to memory, Dm)
and test phase (old/new effects) to examine brain activation related to memory
encoding and retrieval, allowing for selective investigations of these memory sub
processes. In Experiment 1, participants studied own-race (Caucasian) and other
race (Chinese) faces under focused or divided attention. In Experiment 2,
participants studied own-race (Caucasian) and other-race (African American) faces
presented upright or upside down (i.e., inverted). Both experiments showed
decreases in memory performance when attention allocation or holistic processing
was reduced, but these effects were similar for own-race and other-race faces.
Manipulations of holistic processing, but not attention allocation, influenced
the neural other-race effects during memory encoding. Inverted own-race faces
showed similar neural patterns as upright other-race faces, indicating that when
holistic processing of own-race faces was reduced, these faces were encoded
similarly as upright other-race faces. No influences of the experimental
manipulations on other-race effects during memory retrieval were found. The
present study provides the first neural evidence that increased holistic
processing during memory encoding contributes to the other-race effect on face
memory.
PMID- 29943177
TI - Long-term results of two different trans-obturator techniques for surgical
treatment of women with stress and mixed urinary incontinence: a 10-year
randomised controlled study follow-up.
AB - INTRODUCTION: Our aim was to compare the long-term results and complications of
the outside-in (Monarc(r)) versus inside-out (TVT-O(r)) trans-obturator
approaches. METHODS: We performed a 10-year follow-up of our randomised study
from 2007 in which we compared short-term outcomes of both procedures in 120
women. Patients were examined at our department in a tertiary centre between
March and December 2016. The primary aim of the study was to compare the cure and
satisfaction rates of both procedures. The secondary aim was to determine the
incidence of vaginal tape exposures, dyspareunia and LUTS. Statistical analysis
was performed using SPSS Statistics Programme 21.0. Descriptive statistics were
calculated based on basic patient characteristics. Non-parametric tests were used
for comparisons of numerical and Pearson's chi-square for categorical data.
Statistical significance was set at p < 0.05. RESULTS: Of 114 living patients,
82.5% responded. Average follow-up time was 10.2 years. There were no
statistically significant differences between the objective (84.6% for Monarc vs.
94.6% for TVT-O) and subjective cure rates (67.9% vs. 68.3%) or satisfaction
rates (83.9% vs. 78.7%). We found no cases of vaginal tape exposure; 6.4% of all
(10.3% of sexually active) patients reported dyspareunia and 34% reported LUTS
with no significant differences between groups. DISCUSSION: According to our
study, both the inside-out and outside-in procedures showed comparable long-term
efficacy with low complication rates. To our knowledge, this is the longest
randomised study follow-up comparing the cure and satisfaction rates of these two
techniques.
PMID- 29943178
TI - Direct communication between radiologists and patients following imaging
examinations. Should radiologists rethink their patient care?
AB - OBJECTIVES: To investigate patients' perception of the radiology service when the
radiologist communicates the findings to patients. METHODS: After routine MRI,
patients in group 1 (n = 101) were given the opportunity to discuss the findings
with the radiologist. Patients in group 2 (n = 101) left the radiology department
without any personal communication. Subsequently, by means of a questionnaire
designed by an expert psychologist, both groups were asked regarding their
anxiety, emotional attachment to the institute and subjective assessment of
competence. RESULTS: Overall 76 % of all patients were concerned about their
imaging findings without significant difference between both groups (p = 0.179).
Significantly more patients in group 1 (81%) versus group 2 (14%; p < 0.001)
perceived the opportunity to discuss their imaging findings with a radiologist to
be a characteristic of a good radiology consultation. A larger number of patients
in group 1 experienced significantly higher bonding and only wanted in the future
to be examined in the department with communication (p = 0.001) (93%/75%).
Significantly more patients in group 1 regarded the radiology department they
attended as being more competent (mean score 4.72/4.09, p < 0.001). CONCLUSION:
Direct communication of imaging findings from radiologists to patients after an
MRI examination leads to increased confidence in the radiology service and higher
bonding between the patient and radiologist. Radiologists who refrain from direct
communication have a lower bonding to patients and are assessed to have lower
competence from the patient's point of view. KEY POINTS: * Communication between
radiologists and patients leads to an increased bonding affinity. * Direct
communication leads to increased patient confidence in the radiology service. *
Patients perceived discussion with a radiologist of high value.
PMID- 29943179
TI - Correction to: Frequency and characteristics of contralateral breast
abnormalities following recall at screening mammography.
AB - The original version of this article, published on 17 April 2018, unfortunately
contained a mistake.
PMID- 29943180
TI - Comparison between software volumetric breast density estimates in breast
tomosynthesis and digital mammography images in a large public screening cohort.
AB - OBJECTIVES: To compare software estimates of volumetric breast density (VBD)
based on breast tomosynthesis (BT) projections to those based on digital
mammography (DM) images in a large screening cohort, the Malmo Breast
Tomosynthesis Screening Trial (MBTST). METHODS: DM and BT images of 9909 women
(enrolled 2010-2015) were retrospectively analysed with prototype software to
estimate VBD. Software calculation is based on a physics model of the image
acquisition process and incorporates the effect of masking in DM based on
accumulated dense tissue areas. VBD (continuously and categorically) was compared
between BT [central projection (mediolateral oblique view (MLO)] and two-view DM,
and with radiologists' BI-RADS density 4th ed. scores. Agreement and correlation
were investigated with weighted kappa (kappa), Spearman's correlation coefficient
(r), and Bland-Altman analysis. RESULTS: There was a high correlation (r = 0.83)
between VBD in DM and BT and substantial agreement between the software breast
density categories [observed agreement, 61.3% and 84.8%; kappa = 0.61 and K =
0.69 for four (a/b/c/d) and two (fat involuted vs. dense) density categories,
respectively]. There was moderate agreement between radiologists' BI-RADS scores
and software density categories in DM (K = 0.55) and BT (K = 0.47). CONCLUSIONS:
In a large public screening setting, we report a substantial agreement between
VBD in DM and BT using software with special focus on masking effect. This
automated and objective mode of measuring VBD may be of value to radiologists and
women when BT is used as the primary breast cancer screening modality. KEY
POINTS: * There was a high correlation between continuous volumetric breast
density in DM and BT. * There was substantial agreement between software breast
density categories (four groups) in DM and BT; with clinically warranted binary
software breast density categories, the agreement increased markedly. * There was
moderate agreement between radiologists' BI-RADS scores and software breast
density categories in DM and BT.
PMID- 29943181
TI - Characteristics of screen-detected cancers following concordant or discordant
recalls at blinded double reading in biennial digital screening mammography.
AB - OBJECTIVES: To analyse which mammographic and tumour characteristics led to
concordant versus discordant recalls at blinded double reading to further
optimise our breast cancer screening programme. METHODS: We included a
consecutive series of 99,013 screening mammograms obtained between July 2013 and
January 2015. All mammograms were double read in a blinded fashion. Discordant
readings were routinely recalled without consensus or arbitration. During the 2
year follow-up, relevant data of the recalled women were collected. We compared
mammographic characteristics, screening outcome and tumour characteristics
between concordant and discordant recalls. RESULTS: There were 2,543 concordant
recalls (71.4%) and 997 discordant recalls (28.0%). The positive predictive value
of a concordant recall was significantly higher (23.5% vs. 10.0%, p < 0.001). The
proportion of BI-RADS 0 was significantly higher in the discordant recall group
(75.7% vs. 56.3%, p < 0.001). Discordant recalls were more often an asymmetry or
architectural distortion (21.8% vs. 13.2% and 9.3% vs. 6.5%, respectively, p <
0.001). There were no differences in the distribution of DCIS and invasive
cancers and tumour characteristics were comparable for the two groups, except for
a more favourable tumour grade in the discordant recall group (54.7% vs. 39.9%
grade I tumours, p = 0.022). CONCLUSIONS: Screen-detected cancers detected by a
discordant reading show a more favourable tumour grade than cancers diagnosed
after a concordant recall. The higher proportion of asymmetries and architectural
distortions in this group provide a possible target for improving screening
programmes by additional training of screening radiologists and the
implementation of digital breast tomosynthesis. KEY POINTS: * With blinded double
reading of screening mammograms, screen-detected cancers detected by a discordant
reading show a more favourable tumour grade than cancers diagnosed after a
concordant recall. * The proportions of asymmetries and architectural distortions
are higher in case of a discordant reading. * Possible improvement strategies
could target additional training of screening radiologists and the implementation
of digital breast tomosynthesis in breast cancer screening programmes.
PMID- 29943182
TI - Evaluation of T2-W MR imaging and diffusion-weighted imaging for the early post
treatment local response assessment of patients treated conservatively for
cervical cancer: a multicentre study.
AB - OBJECTIVES: To compare MR imaging with or without DWI and clinical response
evaluation (CRE) in the local control evaluation of cervical carcinoma after
radiotherapy. METHODS: In a multicentre university setting, we prospectively
included 107 patients with primary cervical cancer treated with radiotherapy.
Sensitivity and specificity for CRE and MR imaging (with pre-therapy MR imaging
as reference) (2 readers) were evaluated using cautious and strict criteria for
identifying residual tumour. Nested logistic regression models were constructed
for CRE, subsequently adding MR imaging with and without DWI as independent
variables, as well as the pre- to post-treatment change in apparent diffusion
coefficient (delta ADC). RESULTS: Using cautious criteria, CRE and MR imaging
with DWI (reader 1/reader 2) have comparable high specificity (83% and 89%/95%,
respectively), whereas MR imaging without DWI showed significantly lower
specificity (63%/53%) than CRE. Using strict criteria, CRE and MR imaging with
DWI both showed very high specificity (99% and 92%/95%, respectively), whereas MR
imaging without DWI showed significantly lower specificity (89%/77%) than CRE.
All sensitivities were not significantly different. Addition of MR imaging with
DWI to CRE has statistically significant incremental value in identifying
residual tumour (reader 1: estimate, 1.06; p = 0.001) (reader 2: estimate, 0.62;
p = 0.02). Adding the delta ADC did not have significant incremental value in
detecting residual tumour. CONCLUSIONS: DWI significantly increases the
specificity of MR imaging in the detection of local residual tumour. Furthermore,
MR imaging with DWI has significant incremental diagnostic value over CRE,
whereas adding the delta ADC has no incremental diagnostic value. KEY POINTS: *
If MR imaging is used for response evaluation, DWI should be incorporated * MR
imaging with DWI has diagnostic value comparable/complementary to clinical
response evaluation * Inter-reader agreement is moderate to fair for two
experienced radiologist readers * Quantitative measurements of ADC early post
therapy have limited diagnostic value.
PMID- 29943183
TI - Apparent diffusion coefficient as a potential marker for tumour differentiation,
staging and long-term clinical outcomes in gallbladder cancer.
AB - OBJECTIVES: To evaluate the correlation between tumour differentiation or stage
of gallbladder cancer (GBC) and the apparent diffusion coefficient (ADC), as well
as to assess whether ADC value can predict long-term disease-free survival (DFS)
after surgery. METHODS: This retrospective study was approved by the
institutional review board and the requirement for informed consent was waived.
Between March 2008 and June 2016, 79 patients who underwent magnetic resonance
(MR) imaging with diffusion-weighted image and subsequent surgery for GBC were
included in this study. Correlations between quantitative ADC values and tumour
differentiation or stage based on the American Joint Committee on Cancer (AJCC)
were assessed using Spearman's correlation analysis. Prognostic factors for DFS
were identified with multivariate Cox regression analysis using imaging and
clinical characteristics. RESULTS: All patients were classified as having well-
(n = 18), moderately (n = 35) or poorly differentiated GBCs (n = 26). The ADC
value of GBCs was significantly correlated with tumour differentiation and AJCC
stage (p < 0.001 and p < 0.001, respectively). Sixty-nine patients were followed
up for 2.0-92.4 months (median, 23.5 months). On multivariate analysis, the
significant prognostic factor for DFS was not tumour differentiation or AJCC
stage but a binary tumour ADC value (hazard ratio, 4.29; p = 0.009). DFS rates
were significantly different according to the classification of tumour ADC value
(cut-off value = 1.04 * 10-3 mm2/s; p = 0.004). CONCLUSION: The ADC value of GBCs
was significantly correlated with tumour differentiation as well as AJCC stage.
In addition, it predicted long-term outcomes after surgery in patients with GBC.
KEY POINTS: * ADC values of GBC and tumour differentiation were negatively
correlated. * Lower ADC values of GBC were significantly correlated with higher
tumour stage. * Tumour ADC value could be useful for risk stratification of GBC
patients.
PMID- 29943184
TI - Fully automated detection and segmentation of meningiomas using deep learning on
routine multiparametric MRI.
AB - OBJECTIVES: Magnetic resonance imaging (MRI) is the method of choice for imaging
meningiomas. Volumetric assessment of meningiomas is highly relevant for therapy
planning and monitoring. We used a multiparametric deep-learning model (DLM) on
routine MRI data including images from diverse referring institutions to
investigate DLM performance in automated detection and segmentation of
meningiomas in comparison to manual segmentations. METHODS: We included 56 of 136
consecutive preoperative MRI datasets [T1/T2-weighted, T1-weighted contrast
enhanced (T1CE), FLAIR] of meningiomas that were treated surgically at the
University Hospital Cologne and graded histologically as tumour grade I (n = 38)
or grade II (n = 18). The DLM was trained on an independent dataset of 249 glioma
cases and segmented different tumour classes as defined in the brain tumour image
segmentation benchmark (BRATS benchmark). The DLM was based on the DeepMedic
architecture. Results were compared to manual segmentations by two radiologists
in a consensus reading in FLAIR and T1CE. RESULTS: The DLM detected meningiomas
in 55 of 56 cases. Further, automated segmentations correlated strongly with
manual segmentations: average Dice coefficients were 0.81 +/- 0.10 (range, 0.46
0.93) for the total tumour volume (union of tumour volume in FLAIR and T1CE) and
0.78 +/- 0.19 (range, 0.27-0.95) for contrast-enhancing tumour volume in T1CE.
CONCLUSIONS: The DLM yielded accurate automated detection and segmentation of
meningioma tissue despite diverse scanner data and thereby may improve and
facilitate therapy planning as well as monitoring of this highly frequent tumour
entity. KEY POINTS: * Deep learning allows for accurate meningioma detection and
segmentation * Deep learning helps clinicians to assess patients with meningiomas
* Meningioma monitoring and treatment planning can be improved.
PMID- 29943185
TI - Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound
ablation of the prostate.
AB - PURPOSE: To quantitatively assess 12-month prostate volume (PV) reduction based
on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non
perfused volume (NPV), and to compare measurements with predictions of acute and
delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology
review of the Phase I clinical trial of MRI-guided transurethral ultrasound
ablation (TULSA) in patients with localized prostate cancer. MATERIALS AND
METHODS: Treatment day MRI and 12-month follow-up MRI and biopsy were available
for central radiology review in 29 of 30 patients from the published
institutional review board-approved, prospective, multi-centre, single-arm Phase
I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining
PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in
12-month biopsy cores. Reduction of viable PV was compared to predictions based
on the fraction of the prostate covered by the MR-t derived acute thermal
ablation volume (ATAV, 55 degrees C isotherm), delayed thermal ablation volume
(DTAV, 240 cumulative equivalent minutes at 43 degrees C thermal dose isocontour)
and treatment-day NPV. We also report linear and volumetric comparisons between
metrics. RESULTS: After TULSA, the median 12-month reduction in viable PV was
88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53%
volume reduction, and underestimated ATAV and DTAV by 36% and 51%. CONCLUSION:
Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV
(240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue
reduction at 12 months. Immediate post-treatment NPV underestimates tissue
ablation. KEY POINTS: * MRI-guided transurethral ultrasound ablation (TULSA)
achieved an 88% reduction of viable prostate tissue volume at 12 months, in
excellent agreement with expectation from thermal dose calculations. * Non
perfused volume on immediate post-treatment contrast-enhanced MRI represents only
64% of the acute thermal ablation volume (ATAV), and reports only 60% (53%
instead of 88% achieved) of the reduction in viable prostate tissue volume at 12
months. * MR-thermometry-based predictions of 12-month prostate volume reduction
based on 240 cumulative equivalent minute thermal dose volume are in excellent
agreement with reduction in viable prostate tissue volume measured on pre- and 12
month post-treatment T2w-MRI.
PMID- 29943186
TI - CT diagnosis of pleural and stromal invasion in malignant subpleural pure ground
glass nodules: an exploratory study.
AB - OBJECTIVES: To assess the risk of visceral pleural invasion (VPI) and improve the
diagnosis of invasive adenocarcinoma (IA) in pure ground-glass nodules (pGGNs) in
contact with pleura, through a comprehensive analysis of the thin-section CT
features of subpleural malignant pGGNs. METHODS: CT findings and clinical
information of 115 consecutive patients in our hospital between January 2012 and
December 2015 who met the following criteria were retrospectively studied: (a)
thin-section CT within 1 month before surgery proved pGGN in contact with pleura,
and (b) the pGGN was confirmed as malignancy by surgery. Univariate analysis and
a multivariate logistic regression analysis were conducted to identify the
independent risk factors of IA and VPI. RESULTS: No pleural invasion was observed
microscopically in any of the pGGNs. Univariate analysis indicated that tumour
shape (p = 0.004), relative density (p = 0.038) and the existence of pleural
retraction (p < 0.001) were significantly different between the invasive group
and pre- or minimally invasive group. Multivariate logistic regression analysis
revealed that pleural retraction (OR, 5.663; p < 0.001), lobulated tumour shape
(OR, 4.812; p = 0.016) and tumour relative density greater than 1.60 (OR, 4.449;
p = 0.001) were independent risk factors of IA. CONCLUSIONS: Pulmonary
adenocarcinoma manifesting as pGGN generally does not invade the pleura. A
comprehensive consideration of tumour shape, relative density and tumour-pleural
relationship can independently predict IA. KEY POINTS: * This study showed that
pGGN-like adenocarcinoma generally does not invade the pleura. * This study
suggested that persistent pGGN with pleural retraction, lobulated shape and high
relative density (> 1.60) may very likely be invasive adenocarcinoma. * Using
"relative density" can reduce confounding of contrast agent and respiratory
status in analysis of CT images.
PMID- 29943187
TI - Diagnosis of Recurrent Fracture in a Pediatric Cohort.
AB - Significant fracture history in children is defined as having at least one
vertebral fracture, at least 2 fractures by age 10, or at least 3 fractures by
age 19. Between September 2011 and December 2014, clinical data were collected on
children with a significant fracture history that attended a major Australian
children's hospital. Fifty-six patients were identified as having 305 fractures
in total, including 44 vertebral fractures. 18% of patients (10/56) were
diagnosed with osteogenesis imperfecta (OI) by a bone health expert, molecular
testing or both, and they sustained 23% of all fractures (71/305). Analysis of
serum bone biochemistry showed all median values to be within a normal range and
no clinically significant differences between patients with and without OI. The
DXA and pQCT derived bone mineral density (BMD) and bone mineral content (BMC) Z
scores were reduced overall. DXA derived total body and lumbar spine areal BMD
for-age and BMC-for-age Z scores were significantly lower in children who had
vertebral fractures or who were later diagnosed with OI. Similarly, pQCT
performed on radii and tibiae showed Z scores significantly less than zero. pQCT
derived limb muscle cross sectional area Z scores were significantly lower in the
OI subgroup. In conclusion, this study describes the bone phenotype of children
referred to a tertiary hospital clinic for recurrent fractures and highlights a
subset of children with previously undiagnosed OI, but a larger cohort without
classic OI. Thus it can be clinically challenging to differentiate between
children with OI type 1 (mild phenotype) and non-OI children without bone
densitometry and genetic testing. We conclude that recurrent fractures in
children should prompt a comprehensive bone and systemic health assessment to
eliminate an underlying pathology.
PMID- 29943188
TI - Vitamin D Intake and Magnetic Resonance Parameters for Knee Osteoarthritis: Data
from the Osteoarthritis Initiative.
AB - PURPOSE: There is evidence that vitamin D may play a role in the osteoarthritis
(OA) pathogenesis, but the few data available are limited to X-rays and clinical
findings. The aim of this study was to investigate whether a higher intake of
vitamin D was associated with a better architecture of the cartilage of the knee,
assessed with magnetic resonance (MRI), in a large cohort from North America.
METHODS: 783 participants (59.8% females; mean age: 62.3 years) with an MRI
assessment from the Osteoarthritis Initiative were included. Vitamin D dietary
intake was calculated as the sum of food and oral supplementation. A coronal 3D
FLASH with Water Excitation MR sequence of the right knees was used. The strength
of the association between dietary vitamin D intake and knee MRI parameters was
investigated through an adjusted linear regression analysis, reported as
standardized betas with 95% confidence intervals (CIs). RESULTS: Using a linear
regression analysis, adjusted for ten potential confounders, higher vitamin D
intake (reported as an increase in one standard deviation, = 250 IU) corresponded
to significantly higher values of mean cartilage thickness and volume of
cartilage at medial tibia, volume of cartilage and mean cartilage thickness at
central lateral femur, volume of cartilage and mean cartilage thickness at
central medial femur, and volume of cartilage and mean cartilage thickness at
central medial tibial-femoral compartment. CONCLUSIONS: Higher vitamin D intake
is associated with a significantly better architecture of the cartilage of the
knee, also independently taking in account from several potential confounders.
PMID- 29943189
TI - Postural control is associated with muscle power in post-menopausal women with
low bone mass.
AB - : Older women with low bone mass are at higher risk of fracture and there is
limited data on what is associated with risk of falls. We found explosive jumping
to relate most strongly to postural control. It may be beneficial to include
power or speed training into falls prevention programs. INTRODUCTION: Post
menopausal women with low bone mass are at higher risk of bone fractures
subsequent to falls. Understanding the correlates of postural control in this
collective informs intervention design for falls prevention. METHODS: We examined
postural control in single-leg stance on stable and unstable surfaces in 63
community-dwelling post-menopausal women with osteopenia or osteoporosis but
without diagnosed neuromuscular, vestibular or arthritic diseases. Postural
measures were compared to countermovement jump performance (height, force and
power), leg-press strength (10 repetition maximum), calf muscle area and density
(via peripheral quantitative computed tomography), body mass, height and age.
RESULTS: On step-wise regression, peak countermovement jump power and jump height
(p <= 0.014), but not jump force, leg-press strength or calf muscle size, were
related to postural control in single-leg stance on, respectively, an unstable
surface (eyes open) and standing on a stable surface (eyes open). None of the
parameters measured were significantly related to the postural control parameters
in single-leg stance on a stable surface with eyes closed. With testing on the
stable surface, body mass was associated with slow mean centre of pressure
movement speed (p <= 0.030). CONCLUSIONS: Our findings show that, in post
menopausal women with low bone mass, neuromuscular power is a more important
determinant of postural control than muscle strength or size. Our findings
provide evidence to support the integration of power or speed training into falls
prevention and balance training programs in post-menopausal women with osteopenia
and osteoporosis.
PMID- 29943190
TI - Relationship of American Indian blood quantum with osteoporosis risk: a cross
sectional study of American Indian women in Oklahoma.
AB - : Information regarding the prevalence and risk of osteoporosis among American
Indian (AI) women is limited. This study showed that with increasing AI blood
quantum, the prevalence of osteoporosis at the hip based on BMD T-scores
decreased and this appeared to be independent of other risk factors.
INTRODUCTION: This study was designed to investigate the effects of AI blood
quantum (BQ) on osteoporosis prevalence and risk in a cohort of AI women in
Oklahoma. METHODS: Women (n = 301), aged 50 years and older, were recruited to
participate in the Oklahoma American Indian Women's Osteoporosis Study. Baseline
bone density, fracture history, bone biochemical markers, and potential risk
factors were assessed. Participants were stratified by AI BQ into BQ1 <= 25%, BQ2
= 25-49%, BQ3 = 50-74%, and BQ4 = 75-100%. The effects of BQ on the prevalence
and risk of osteoporosis were evaluated. RESULTS: Based on T-scores, one in
approximately eight women in the study was osteoporotic at one or more sites. The
prevalence of osteoporosis decreased (p < 0.05) with increasing BQ, especially at
the hip, trochanteric, and intertrochanter regions. No differences in bone
specific alkaline phosphatase and C-telopeptide were observed across BQ that
could account for the differences in bone density. 25-OH vitamin D decreased with
increasing BQ, but mean for each BQ1-4 was > 40 ng/mL. Fracture history did not
differ across BQ, and though 52% of the population consumed less than the RDA for
calcium, no effect of BQ was observed. CONCLUSIONS: In this cohort of women who
identified as AI, greater Indian BQ was associated with a decrease in the
prevalence of osteoporosis.
PMID- 29943191
TI - Imaging-based outcome prediction in patients with intracerebral hemorrhage.
AB - Besides the established spot sign in computed tomography angiography (CTA),
recently investigated imaging predictors of hematoma growth in noncontrast
computed tomography (NCCT) suggest great potential for outcome prediction in
patients with intracerebral hemorrhage (ICH). Secondary hematoma growth is an
appealing target for therapeutic interventions because in contrast to other
determined factors, it is potentially modifiable. Even more initial therapy
studies failed to demonstrate clear therapeutic benefits, there is a need for an
effective patient selection using imaging markers to identify patients at risk
for poor outcome and thereby tailor individual treatments for every patient.
Hence, this review gives an overview about the current literature on NCCT imaging
markers for neurological outcome prediction and aims to clarify the association
with the established spot sign. Moreover, it demonstrates the clinical impact of
these parameters and gives a roadmap for future imaging research in patients with
intracerebral hemorrhage.
PMID- 29943192
TI - Phase II study of pazopanib in combination with paclitaxel in patients with
metastatic melanoma.
AB - PURPOSE: This phase II study evaluated the safety and clinical activity of
pazopanib, a potent and mutlitargeted tyrosine kinase inhibitor (TKI) of vascular
endothelial growth factor receptors (VEGFRs)-1, -2 and -3, platelet-derived
growth factor receptor (PDGFR)-alpha and beta, and cKit, in combination with
metronomic paclitaxel in patients with metastatic melanoma. EXPERIMENTAL DESIGN:
Sixty chemotherapy-naive patients received pazopanib at a starting dose of 800 mg
daily in combination with metronomic dosing of paclitaxel 80 mg/m2 weekly thrice
every 4 weeks. The primary endpoint was 6-month progression-free survival (PFS)
rate, while secondary endpoints included 1-year overall survival rate, RECIST
response rates, progression-free survival rates and median overall survival.
Prior BRAF-targeted therapy or checkpoint inhibitors were permitted. RESULTS: The
6-month PFS rate was 68%, with a 1-year OS rate of 48%. Objective response rate
was 37% comprising one complete and 20 partial responses. Stable disease at 8
weeks was noted in 32 patients (55%) with an overall clinical benefit rate of
93%. Six-month median progression-free survival was 8 months and median OS was
12.7 months. The most frequently (> 15%) reported non-hematologic, treatment
related adverse events were fatigue, diarrhea, hypertension, transaminitis and
peripheral neuropathy. Treatment-related non-fatal bowel perforation, a known
class effect, occurred in one patient. No significant association was noted
between plasma levels of pazopanib and response. CONCLUSIONS: The combination of
pazopanib and metronomic paclitaxel was well-tolerated, demonstrating significant
activity in metastatic melanoma. Further evaluation of this combination is
warranted.
PMID- 29943195
TI - [Urology in Munich celebrating its 80th anniversary : Memories of the
establishment and development from an eyewitness].
AB - The Department of Urology, Municipal Hospital, Thalkirchnerstr. 48, Munich (1938
1984) is justly reputed as one of the germ-cells of German Urology, not only by
Prof. May's protagonism for an independent urology, but also by the multiple,
especially technical innovations under the successors, which are fundamentals for
the modern urology.
PMID- 29943193
TI - Nucleo-cytoplasmic transport of TDP-43 studied in real time: impaired microglia
function leads to axonal spreading of TDP-43 in degenerating motor neurons.
AB - Transactivating DNA-binding protein-43 (TDP-43) deposits represent a typical
finding in almost all ALS patients, more than half of FTLD patients and patients
with several other neurodegenerative disorders. It appears that perturbation of
nucleo-cytoplasmic transport is an important event in these conditions but the
mechanistic role and the fate of TDP-43 during neuronal degeneration remain
elusive. We have developed an experimental system for visualising the perturbed
nucleocytoplasmic transport of neuronal TDP-43 at the single-cell level in vivo
using zebrafish spinal cord. This approach enabled us to image TDP-43-expressing
motor neurons before and after experimental initiation of cell death. We report
the formation of mobile TDP-43 deposits within degenerating motor neurons, which
are normally phagocytosed by microglia. However, when microglial cells were
depleted, injury-induced motor neuron degeneration follows a characteristic
process that includes TDP-43 redistribution into the cytoplasm, axon and
extracellular space. This is the first demonstration of perturbed TDP-43
nucleocytoplasmic transport in vivo, and suggests that impairment in microglial
phagocytosis of dying neurons may contribute towards the formation of
pathological TDP-43 presentations in ALS and FTLD.
PMID- 29943196
TI - Chronic solvent-induced encephalopathy: course and prognostic factors of
neuropsychological functioning.
AB - PURPOSE: Working in conditions with daily exposure to organic solvents for many
years can result in a disease known as chronic solvent-induced encephalopathy
(CSE). The aims for this study were to describe the neuropsychological course of
CSE after first diagnosis and to detect prognostic factors for neuropsychological
impairment after diagnosis. METHODS: This prospective study follows a Dutch
cohort of CSE patients who were first diagnosed between 2001 and 2011 and
underwent a second neuropsychological assessment 1.5-2 years later. Cognitive
subdomains were assessed and an overall cognitive impairment score was
calculated. Paired t tests and multivariate linear regression analyses were
performed to describe the neuropsychological course and to obtain prognostic
factors for the neuropsychological functioning at follow-up. RESULTS: There was a
significant improvement on neuropsychological subdomains at follow-up, with
effect sizes between small and medium (Cohen's d 0.27-0.54) and a significant
overall improvement of neuropsychological impairment with a medium effect size
(Cohen's d 0.56). Prognostic variables for more neuropsychological impairment at
follow-up were a higher level of neuropsychological impairment at diagnosis and
having a comorbid diagnosis of a psychiatric disorder at diagnosis. CONCLUSIONS:
Results are in line with previous research on the course of CSE, stating that CSE
is a non-progressive disease after cessation of exposure. However, during follow
up the percentage patients with permanent work disability pension increased from
14 to 37%. Preventive action is needed in countries where exposure to organic
solvents is still high to prevent new cases of CSE.
PMID- 29943197
TI - Combined resection of the transpancreatic common hepatic artery preserving the
gastric arterial arcade without arterial reconstruction in
hepatopancreatoduodenectomy: a case report.
AB - BACKGROUND: Surgeons sometimes must plan pancreatoduodenectomy (PD) for patients
with a variant common hepatic artery (CHA) branching from the superior mesenteric
artery (SMA) penetrating the pancreatic parenchyma, known as a transpancreatic
CHA (tp-CHA). CASE PRESENTATION: A 67-year-old man was admitted to our hospital
because of liver dysfunction. A duodenal tumor was identified by gastrointestinal
endoscopy, and a biopsy revealed a neuroendocrine tumor. Computed tomography
showed multiple metastases in the left three sections of the liver. As an
anatomical variant, the CHA branched from the SMA and passed through the
parenchyma of the pancreatic head, and all hepatic arteries branched from the
CHA. Furthermore, the arcade between the left and right gastric artery (RGA) was
detected, and the RGA branched from the root of the left hepatic artery. PD and
left trisectionectomy of the liver were performed. The tp-CHA was resected with
the pancreatic head, and the gastric arterial arcade was preserved to maintain
the right posterior hepatic arterial flow. Postoperatively, there were no signs
of hepatic ischemia. CONCLUSIONS: When planning PD, including
hepatopancreatoduodenectomy, for patients with a tp-CHA, surgeons should simulate
various situations for maintaining the hepatic arterial flow. The preservation of
the gastric arterial arcade is an option for maintaining the hepatic arterial
flow to avoid arterial reconstruction.
PMID- 29943198
TI - Patterns of coronal curve changes in forward bending posture: a 3D ultrasound
study of adolescent idiopathic scoliosis patients.
AB - PURPOSE: The Adam's forward bending test is the most commonly used approach to
assess the spine deformity in adolescent idiopathic scoliosis (AIS) patients.
However, there are noticeable differences in the hump appearance from standing to
forward bending. This phenomenon has yet to be understood due to limitations of
conventional radiographs. This study aimed to investigate effects of postural
change in the spine deformity in the coronal plane of AIS patients using a 3D
ultrasound imaging system. METHODS: This was a prospective study that recruited
72 AIS patients at a single institute. All patients were scanned twice in the
sitting and sitting forward bending postures. A coronal ultrasound image showing
the spinal curvature was generated after each scan and the spinous process angle
(SPA) representing the deformity was manually measured from it. Correlation of
SPAs under sitting and sitting forward bending postures was analyzed. RESULTS: In
the comparison test, it was noted that there were three types of spine profile
alternation after the postural change. In types I and II, the SPA angle numbers
were the same before and after forward bending and only SPA values changed. In
type III, the two curvatures were changed to one curvature in the forward bending
posture. Moderate correlation was observed between the angles obtained in the two
postures (r = 0.55, p < 0.001). CONCLUSIONS: Spine deformities of AIS patients
vary with different postures. The patterns of changes in sitting and sitting
forward bending postures are highly subject dependent. These slides can be
retrieved under Electronic Supplementary Material.
PMID- 29943200
TI - Correction to: Residual Renal Function and Obstructive Sleep Apnea in Peritoneal
Dialysis: A Pilot Study.
AB - The original version of this article unfortunately contained a mistake in the
article title. The correct article title is "Residual Renal Function and
Obstructive Sleep Apnea in Peritoneal Dialysis: A Pilot Study".
PMID- 29943199
TI - A residue of motif III positions the helicase domains of motor subunit HsdR in
restriction-modification enzyme EcoR124I.
AB - Type I restriction-modification enzymes differ significantly from the type II
enzymes commonly used as molecular biology reagents. On hemi-methylated DNAs type
I enzymes like the EcoR124I restriction-modification complex act as conventional
adenine methylases at their specific target sequences, but unmethylated targets
induce them to translocate thousands of base pairs through the stationary enzyme
before cleaving distant sites nonspecifically. EcoR124I is a superfamily 2 DEAD
box helicase like eukaryotic double-strand DNA translocase Rad54, with two RecA
like helicase domains and seven characteristic sequence motifs that are
implicated in translocation. In Rad54 a so-called extended region adjacent to
motif III is involved in ATPase activity. Although the EcoR124I extended region
bears sequence and structural similarities with Rad54, it does not influence
ATPase or restriction activity as shown in this work, but mutagenesis of the
conserved glycine residue of its motif III does alter ATPase and DNA cleavage
activity. Through the lens of molecular dynamics, a full model of HsdR of
EcoR124I based on available crystal structures allowed interpretation of
functional effects of mutants in motif III and its extended region. The results
indicate that the conserved glycine residue of motif III has a role in
positioning the two helicase domains.
PMID- 29943201
TI - Beyond 35 years of Parkinson's disease: a comprehensive clinical and instrumental
assessment.
AB - BACKGROUND: We sought to characterize the clinical, neuropsychological,
electrophysiological, and neuroimaging features of Parkinson's disease (PD) after
over 35 years since the onset of motor symptoms. METHODS: Five consecutively
consenting PD patients treated with subthalamic nucleus deep brain stimulation
(STN-DBS) were recruited in a cross-sectional study of motor (Unified PD Rating
Scale section-III), non-motor (Non-Motor Symptoms Scale), autonomic (Scale for
Outcome in PD-Autonomic), and neuropsychological features associated with the
very advanced phase of PD. In addition, patients underwent neurophysiological
(autonomic tests and nerve conduction studies) and neuroimaging (brain MRI, 123I
FP-CIT SPECT, and 123I-MIBG myocardial scintigraphy) studies, as well as a
genetic analysis of 34 genes and single nucleotide polymorphisms associated with
PD. RESULTS: There was a sustained motor response to L-dopa (range 14.4-35.6%),
STN-DBS (23.3-38.4%), and L-dopa plus STN-DBS (37.8-63.0%). There were mild-to
moderate non-motor symptoms (range 19-83 on a scale of 0 to 360) and autonomic
dysfunction (8-28 on a scale of 0-69). Two patients were demented, one had mild
cognitive impairment, and two were cognitively preserved. Three patients had a
sensory-axonal peripheral neuropathy and two a moderate-to-severe autonomic
neuropathy. All cases showed a complete nigro-striatal dopaminergic denervation
and a severe cardiovascular noradrenergic denervation. The brain MRI revealed
only moderate frontal atrophy. The genetic tests were unremarkable. CONCLUSIONS:
Even after more than 35 years of disease, L-dopa and STN-DBS remain effective on
PD cardinal symptoms. Although axial, autonomic, and neuropsychological features
may become key determinants of disability, some patients maintain a satisfactory
quality of life, without significant motor and non-motor impairment.
PMID- 29943203
TI - Optimizing Rheumatoid Arthritis Patients for Surgery.
AB - PURPOSE OF REVIEW: The purpose of this review is to guide providers on how best
to optimize the health of patients with rheumatoid arthritis (RA) planning
surgery, to reduce risk and complications and achieve the best outcomes. RECENT
FINDINGS: The American College of Rheumatology (ACR) and the American Association
of Hip and Knee Surgeons (AAHKS) have issued a recent guideline on perioperative
management of antirheumatic medications in patients with RA. Patients with RA
will continue to need surgery. Newer literature is helping to plan the
perioperative period to help reduce complications and improve outcomes.
PMID- 29943202
TI - SEEG-guided radiofrequency coagulation (SEEG-guided RF-TC) versus anterior
temporal lobectomy (ATL) in temporal lobe epilepsy.
AB - BACKGROUND: Stereoelectroencephalography-guided radiofrequency thermocoagulation
(SEEG-guided RF-TC) is a super-selective procedure. Hippocampus has a limited
volume and is widely accessible to SEEG so that SEEG-guided RF-TC could be an
alternative to the anterior temporal lobectomy (ATL) in case of temporal lobe
epilepsy (TLE) syndrome. OBJECTIVE: To compare seizure-free rate at 1-year follow
up between patients undergoing SEEG-guided RF-TC and patients undergoing ATL in
TLE over a 15-year period. METHODS: All patients had a drug-resistant epilepsy
and underwent SEEG after non-conclusive phase I investigations suspecting a TLE.
Two groups were selected according to the procedure which the patients underwent
(ATL or SEEG-guided RF-TC); TLE had to be confirmed by SEEG in the two groups.
The primary outcome was seizure freedom at 1 year. The secondary outcome was
response (at least 50% reduction of seizure frequency) at 1 year. In case of
persistent seizures after SEEG-guided RF-TC, ATL was performed. RESULTS: A total
of 21 patients underwent SEEG-guided RF-TC and 49 ATL. At 12 months, none of the
patients of the SEEG-guide RF-TC group was seizure free, while 37 (75.5%) in the
ATL group were so (p < 0.001). Ten patients (47.6%) were responders after 12
months of follow-up after SEEG-guided RF-TC; all patients in the ATL group who
were seizure free were responders. CONCLUSION: SEEG-guided RF-TC is not as
effective as ATL in TLE. As no memory impairment following SEEG-guided RF-TC was
found, patients with dominant mesial involvement for whom hippocampectomy is not
an option could benefit from the technique.
PMID- 29943204
TI - Diabetes Management Among Arab Americans Who Sought Care at a Large Metropolitan
Hospital System in Michigan.
AB - To estimate and compare the management of diabetes among Arab, Asian, non
Hispanic Black, and non-Hispanic Whites attending a large health system in
metropolitan Detroit. Data were electronically abstracted for 6622 adult patients
with diabetes. Dependent variables were uptake of A1c testing and results, LDL-C
testing and results, and eye examination frequency. The independent variable was
race/ethnicity. Logistic regression models were used to examine the association
between Arab Americans and non-Hispanic Whites for each of the dependent
variables while controlling for confounders. Arab Americans were 38% more likely
than non-Hispanic Whites to report an A1c > 7% (OR 1.38; 95% CI 1.03, 1.87). Arab
Americans were 62% less likely to receive an eye exam compared to non-Hispanic
Whites (OR 1.62; 95% CI 1.21, 2.17). Population based studies about diabetes
management among Arab Americans will facilitate tailored interventions aimed at
preventing/delaying diabetes complications and reducing premature mortality due
to diabetes.
PMID- 29943205
TI - Anal gland adenocarcinoma in situ with pagetoid spread: a case report.
AB - BACKGROUND: Anal gland carcinoma with perianal Paget's disease is rare, and anal
gland carcinoma in situ is extremely rare. No cases of anal gland carcinoma in
situ with pagetoid spread have been previously reported. CASE PRESENTATION:
Physical examination in a 75-year-old woman revealed an erythematous, inflamed,
perianal skin lesion. Neither colposcopy, cystoscopy, colonoscopy, computed
tomography, nor magnetic resonance imaging showed evidence of malignant
genitourinary or gastrointestinal lesions. Histopathological examination of a
biopsy specimen showed many Paget's cells in the perianal skin lesion and no
malignant cells in the rectal or vaginal mucosa. Therefore, primary extramammary
Paget's disease of the anogenital region was suspected, and we performed anus
preserving wide local excision. However, immunohistochemistry revealed a
diagnosis of secondary extramammary Paget's disease due to adenocarcinoma arising
from the anal gland. We therefore proceeded with a radical operation.
Histopathological examination showed no residual cancer cells. The final
diagnosis was anal gland adenocarcinoma in situ with pagetoid spread in the
perianal skin. CONCLUSIONS: This is the first case report of anal gland
adenocarcinoma in situ with pagetoid spread. We recommend immunohistochemical
analysis of biopsy and locally resected specimens to obtain an accurate diagnosis
and determine the appropriate treatment when there is no visible tumor.
PMID- 29943206
TI - SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 influences flowering time, lateral
branching, oil quality, and seed yield in Brassica juncea cv. Varuna.
AB - SOC1, a MADS-box type II transcription factor, integrates environmental and
endogenous cues to promote flowering in angiosperms. Recent reports implicating
SOC1 in roles beyond floral transition prompted functional characterization of
SOC1 in polyploid rapeseed mustard genomes. Gene characterization in Brassicas
necessitates analysis of composite homeolog function. While insertional
mutagenesis is untenable in Brassicas owing to gene redundancy, gain-of-function
approach entails serial characterization of individual homeologs. Herein, we
demonstrate modulated floral promotive effects in natural variants of Brassica
SOC1 and provide lateral branching as a probable outcome of polyploidy-induced
gene diversification. Ectopic expression of two B genome specific SOC1 variants
in Arabidopsis thaliana resulted in differential floral acceleration and
manifestation of multiple vegetative rosettes. Characterization of composite
homeolog function in B. juncea via introgression of Brassica SOC1 specific
artificial miRNA, designed to target homeologs, also exhibited modifications in
floral transition and lateral branching. Comprehensive analysis of field
performance of B. juncea transgenics displayed altered fitness across 11
agronomic traits. Crucially, reduced SOC1 levels directly impacted two
developmental traits, namely, flowering time and number of lateral branches which
in turn influenced several dependent agronomic traits. While delayed flowering
and crop maturity resulted in altered fatty acid composition with higher SFA and
lower PUFA in transgenics relative to controls, reduction in overall count of
lateral branches caused a concomitant decrease in silique count which ultimately
impacted total seed yield in transgenics. Statistical analysis revealed number of
secondary branches as the most critical trait influencing seed yield. Based on
our findings, we propose enhancing levels Brassica SOC1, a key target, for
achieving earliness in flowering, improved seed yield and oil quality, and
studying trait trade-offs.
PMID- 29943207
TI - The efficiency of inspiratory muscle training in patients with ankylosing
spondylitis.
AB - Ankylosing spondylitis (AS) is an inflammatory rheumatic disease affecting mainly
the axial skeleton and sacroiliac joints. The aim of the current study was to
investigate the effects of inspiratory muscle training (IMT) on respiratory
muscles and functional exercise capacity, as well as on the specific outcomes of
the disease in AS patients. A total of 32 AS patients (mean age 37.37 +/- 10.41
years) were randomly assigned as the Training Group (TG) (n = 16, mean age =
35.62 +/- 8.18 years) who received IMT + conventional exercise, and the Control
Group (CG) (n = 16, mean age = 39.12 +/- 12.26 years) who only performed the
conventional exercise program. All the subjects were evaluated at baseline and at
the end of the 8th week. Respiratory muscle strength was assessed by measuring
the maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax).
Functional exercise capacity was measured using the 6-min walk test (6MWT). The
Bath AS Disease Activity Index (BASDAI), Bath AS Disease Function Index and Bath
AS Metrology Index were used for activity, function and basic measurements of the
disease. A statistically significant improvement was determined in the PImax (p =
0.000), PEmax (p = 0.002), 6MWT (p = 0.041) and BASDAI (p = 0.049) values in the
TG after training. There was a significant difference between baseline and after
conventional exercise in terms of PEmax (p = 0.017) in the CG. The PEmax (p =
0.001) and the 6MWT (p = 0.053) values were significantly better in the TG. The
results of this study demonstrated that IMT in addition to conventional exercises
increased inspiratory muscle strength, functional exercise capacity and
positively affected the disease activity in AS.
PMID- 29943208
TI - Preclinical Development of Cell-Based Products: a European Regulatory Science
Perspective.
AB - PURPOSE: This article describes preclinical development of cell-based medicinal
products for European markets and discusses European regulatory mechanisms open
to developers to aid successful product development. Cell-based medicinal
products are diverse, including cells that are autologous or allogeneic, have
been genetically modified, or not, or expanded ex vivo, and applied systemically
or to an anatomical site different to that of their origin; comments applicable
to one product may not be applicable to others, so bespoke development is needed,
for all elements - quality, preclinical and clinical. METHODS: After establishing
how the product is produced, proof of potential for therapeutic efficacy, and
then safety, of the product need to be determined. This includes understanding
biodistribution, persistence and toxicity, including potential for malignant
transformation. These elements need to be considered in the context of the
intended clinical development. RESULTS: This article describes regulatory
mechanisms available to developers to support product development that aim to
resolve scientific issues prior to marketing authorization application, to enable
patients to have faster access to the product than would otherwise be the case.
CONCLUSIONS: Developers are encouraged to be aware of both the scientific issues
and regulatory mechanisms to ensure patients can be supplied with these products.
PMID- 29943209
TI - Continuous Single-Step Wet Granulation with Integrated in-Barrel-Drying.
AB - PURPOSE: It was investigated if continuous wet granulation and drying could be
combined in a twin-screw granulator with the aim to provide (pre-)dried granules
in a single-step process, i.e. in-barrel-drying. METHODS: To have a consistent
and robust material propulsion mechanism, a twin-screw granulator was divided
into two compartments. One compartment was operated at lower temperature to
granulate and to pre-heat the material, while another compartment was operated at
very high temperature to evaporate the granulation liquid as rapidly as possible.
Design of experiments was used to investigate the in-barrel-drying process in
detail. The process was further investigated for twin-screw wet granulation with
API suspension feed, and compared against traditional fluidised-bed drying.
Granule and compact properties were evaluated to study the process impact on the
product quality. RESULTS: In-barrel-drying was demonstrated as feasible and
yielded completely dried and granulated material at specific settings. The
evaporation zone temperature and the processed mass of water were identified as
key parameters to balance the evaporation capacity of the process and the
material throughput. Granules and compacts showed an acceptable product quality.
CONCLUSIONS: In-barrel-drying can be used to condense the wet granulation and
drying process steps into one piece of equipment, thereby limiting or even
omitting downstream drying process steps.
PMID- 29943211
TI - Physicochemical and Antioxidant Properties of Riboflavin in Dextran70/HSA
Systems.
AB - Physicochemical properties of Riboflavin (Vitamin B2) (RF), in Dextran 70 (Dx70)
(a biological relevant glucidic type macromolecule) and Human Serum Albumin (HSA)
(a carrier/transport protein) based system, have been studied by absorption,
fluorescence, circular dichroism and electrochemistry. No significant changes on
the fluorescence of RF in Dx70/HSA systems with and without the influence of
temperature (30-60 degrees C range) were observed. No changes on the intrinsic
Tryptophan fluorescence in Dx70/RF/HSA system, have been evidenced. HSA secondary
structure when RF binds in Dx70/RF/HSA systems, with a renaturation effect of
Dx70, was found. In Dx70/RF/HSA system the major process which RF undergoes is
the proton transfer, Ered = -0.43 V. Using the chemiluminescence method, an
improvement of the antioxidant activity of RF into the Dx70/RF/HSA system, was
also found. RF concentration in Dx70/RF/HSA systems is important in RF oxidative
damages when it reacts with target molecules and thus promotes their oxidation.
The results have relevance in the oxidative stress process and in pharmaceutical
formulations containing RF.
PMID- 29943210
TI - Pathogenesis of Enteropathy-Associated T Cell Lymphoma.
AB - PURPOSE OF REVIEW: To provide an update on the pathogenesis of enteropathy
associated T cell lymphoma (EATL) and its relationship with refractory celiac
disease (RCD), in light of current knowledge of immune, genetic, and
environmental factors that promote neoplastic transformation of intraepithelial
lymphocytes (IELs). RECENT FINDINGS: EATL frequently evolves from RCD type II
(RCD II) but can occur "de novo" in individuals with celiac disease. Recurrent
activating mutations in members of the JAK/STAT pathway have been recently
described in EATL and RCD II, which suggests deregulation of cytokine signaling
to be an early event in lymphomagenesis. Intraepithelial T cells are presumed to
be the cell of origin of EATL (and RCD II). Recent in vitro molecular and
phenotypic analyses and in vivo murine studies, however, suggest an origin of RCD
II from innate IELs (NK/T cell precursors), which could also be the cell of
origin of RCD II-derived EATL. The immune microenvironment of the small
intestinal mucosa in celiac disease fosters the development of EATL, often in a
multistep pathway.
PMID- 29943213
TI - Interactive effects of Magnaporthe inoculation and nitrogen doses on the plant
enzyme machinery and phyllosphere microbiome of resistant and susceptible rice
cultivars.
AB - Severity of plant diseases is often influenced by the availability of nutrients,
particularly N; however, its effect on the phyllosphere microbiome in foliar
pathogen challenged plants is less investigated in rice. The tripartite
interaction among the fungal pathogen (Magnaporthe oryzae), rice cultivars
(basmati and non-basmati, blast resistant or susceptible) and nitrogen (N)
fertilization (0, 120 and 180 N) was investigated. Plant growth, elicitation of
defense responses and abundance of microbial members in the rice phyllosphere
were monitored using biochemical and molecular methods. In general,
photosynthetic pigments were distinct for each cultivar, and optimal N doses led
to higher values. The susceptible var. CO-39 and resistant CO-39I exhibited
higher contents of photosynthetic pigments and micronutrients such as zinc in
leaves in response to N doses. Elicitation of defense and hydrolytic enzymes was
significantly influenced by pathogen inoculation and modulated by N doses, but
varietal effects were distinct. Scoring indices emphasized the pathogen
susceptibility of var. CO-39 and PB-1, which showed almost 40-60% higher values
than the resistant cultivars; the interactions of cultivars and N doses was also
significant. Characteristic changes were recorded in the abundances of the gene
copies, particularly, with an overall increase in the number of cyanobacterial
16S rRNA, and bacterial amoA in pathogen-challenged treatments, while nifH gene
copies exhibited a reducing trend with increasing N doses, in the presence or
absence of pathogen. The varietal differences in the cause and effect
relationships can be valuable in crop protection for more effective foliar
application of pesticides or biocontrol agents.
PMID- 29943212
TI - En route into chloroplasts: preproteins' way home.
AB - Chloroplasts are the characteristic endosymbiotic organelles of plant cells which
during the course of evolution lost most of their genetic information to the
nucleus. Thus, they critically depend on the host cell for allocation of nearly
their complete protein supply. This includes gene expression, translation,
protein targeting, and transport-all of which need to be tightly regulated and
perfectly coordinated to accommodate the cells' needs. To this end, multiple
signaling pathways have been implemented that interchange information between the
different cellular compartments. One of the most complex and energy consuming
processes is the translocation of chloroplast-destined proteins into their target
organelle. It is a concerted effort from chaperones, receptor proteins, channels,
and regulatory elements to ensure correct targeting, efficient transport, and
subsequent folding. Although we have discovered and learned a lot about protein
import into chloroplasts in the last decades, there are still many open questions
and debates about the roles of individual proteins as well as the mechanistic
details. In this review, I will summarize and discuss the published data with a
focus on the translocation complex in the chloroplast inner envelope membrane.
PMID- 29943214
TI - Correction to: Gene therapy knockdown of VEGFR2 in retinal endothelial cells to
treat retinopathy.
AB - The article "Gene therapy knockdown of VEGFR2 in retinal endothelial cells to
treat retinopathy", written by "Aaron B. Simmons, Colin A. Bretz, Haibo Wang,
Eric Kunz, Kassem Hajj, Carson Kennedy, Zhihong Yang, Thipparat Suwanmanee, Tal
Kafri and M. Elizabeth Hartnett", was originally published electronically on the
publisher's internet portal (currently SpringerLink) on 05 May 2018 without open
access. With the author(s)' decision to opt for Open Choice the copyright of the
article changed on 20 June 2018 to (c) The Author(s) 2018 and the article is
forthwith distributed under the terms of the Creative Commons Attribution 4.0
International License ( http://creativecommons.org/licenses/by/4.0/ ), which
permits use, duplication, adaptation, distribution and reproduction in any medium
or format, as long as you give appropriate credit to the original author(s) and
the source, provide a link to the Creative Commons license and indicate if
changes were made.
PMID- 29943215
TI - Adsorptive removal of harmful algal species Microcystis aeruginosa directly from
aqueous solution using polyethylenimine coated polysulfone-biomass composite
fiber.
AB - In recent times, the treatment of harmful algal blooms (HABs) became an important
environmental issue to preserve and remediate water resources globally. In the
present study, the adsorptive removal of harmful algal species Microcystis
aeruginosa directly from an aqueous medium was attempted. Waste biomass
(Escherichia coli) was immobilized using polysulfone and coated using the
cationic polymer polyethylenimine (PEI) to generate PEI-coated polysulfone
biomass composite fiber (PEI-PSBF). The density of M. aeruginosa in an aqueous
medium (BG11) was significantly decreased by treatment with PEI-PSBF.
additionally, analysis using FE-SEM, confirmed that the removal of M. aeruginosa
algal cells by PEI-PSBF was caused by the adsorption mechanism. According to the
profiles of phosphorus for the algal cell growth in M. aeruginosa cultivating
samples, we found that the adsorbed M. aeruginosa onto the PEI-PSBF lost their
biological activity compared to the non-treated M. aeruginosa cells.
PMID- 29943216
TI - Long-term outcomes following partial atrioventricular septal defect (AVSD) repair
in Ireland.
AB - BACKGROUND: We describe the long-term results of partial atrioventricular septal
defect (AVSD) repair in a single centre encompassing a 22-year period. Described
are rates of survival, reoperation and complications. METHODS: We performed a
retrospective review of 556 patients undergoing AVSD repair to identify the 51
patients who underwent partial AVSD repair in Our Lady's Children's Hospital,
Crumlin, Ireland, between 1993 and 2015 with long-term follow-up where available.
RESULTS: A total of 29 (56.8%) of patients were male and mean age at operation
was 3.32 years. Mean weight was 13.2 kg. Trisomy 21 was present in 29 (56.8%).
Five patients (9.6%) had undergone prior surgery. Mean cardiopulmonary bypass
time was 89 +/- 36 min and mean aortic cross-clamp time was 57 +/- 28 min. One
patient underwent partial AVSD repair and concomitant tracheal resection and
extracorporeal membrane oxygenation decannulation. One patient was managed with
suture atrial septal defect (ASD) closure, the remainder with patch repair of ASD
and mitral cleft closure. The length of hospital stay was 9 +/- 5 days. Median
follow-up was 6.06 years (IQR, 1.65-10.2 years). There were no early mortalities.
One patient died 1 year following surgery (1.9%). One patient required
reoperation at an interval of 2 years for severe mitral regurgitation (1.9%).
CONCLUSIONS: Short- and long-term survival following partial AVSD repair in
Ireland revealed excellent results compared with other published series.
Reoperation incidence also compared excellently with other reports published in
the literature.
PMID- 29943217
TI - Topical Ivermectin in the Treatment of Papulopustular Rosacea: A Systematic
Review of Evidence and Clinical Guideline Recommendations.
AB - INTRODUCTION: Rosacea is a chronic inflammatory skin disease with different
phenotypes. There is accumulating evidence that the commensal Demodex mite is
linked to papulopustular rosacea. Established treatment options, including
topical metronidazole, azelaic acid, and tetracyclines, are thought to work
through their anti-inflammatory effects. However, none of these therapies have
been shown to be curative and are associated with frequent relapses. Therefore,
new and improved treatment options are needed. Topical ivermectin 1.0% cream is a
new option having both anti-inflammatory and acaricidal activity against Demodex
mites which might pave the way to a more etiologic approach. Its use has now been
widely adopted by clinical guidelines. The objective was to review the evidence
and clinical guideline recommendations concerning ivermectin 1.0% cream in the
treatment of papulopustular rosacea. METHODS: A systematic review of both medical
literature and clinical guideline recommendations was conducted. Numbers needed
to treat (NNT) were calculated for relevant dichotomous outcomes (e.g., relapse
rate and achieving full lesion clearance) to compare ivermectin with other
established treatment options for rosacea. RESULTS: The search identified three
randomized trials, three extension studies, and two meta-analyses. Ivermectin has
only been tested in moderate-to-severe papulopustular rosacea. Ivermectin is an
effective treatment option for papulopustular rosacea and seems to be more
effective than metronidazole (NNT = 10.5) at 12 weeks of treatment. Although
ivermectin was numerically more effective than metronidazole at week 36 in
preventing relapse (NNT = 17.5), relapse after discontinuation of treatment in
both groups was common with 62.7% and 68.4% of patients relapsing. Based on
limited generalizability of available evidence, clinical guidelines have yielded
different treatment algorithms and, in some areas, conflicting recommendations.
CONCLUSION: Topical ivermectin is an effective option in the treatment of
papulopustular rosacea. Although ivermectin seems to be more effective than
topical metronidazole, with both treatment options about two-thirds of patient
relapsed within 36 weeks after discontinuation of treatment. More research is
needed to establish the clinical benefit of ivermectin's acaricidal action in
preventing relapse compared to other non-etiologic treatment approaches.
PMID- 29943218
TI - Muscle-invasive bladder cancer organ-preserving therapy: systematic review and
meta-analysis.
AB - PURPOSE: To determine the effectiveness and harms of bladder-preserving trimodal
therapy (TMT) as a first-line treatment versus radical cystectomy (RC) plus
radical pelvic lymphadenectomy in the treatment of muscle-invasive bladder cancer
in terms of overall survival. METHODS: We included parallel clinical trials and
prospective and retrospective cohort studies that included patients older than 18
years old, diagnosed with muscle-invasive bladder cancer, who underwent TMT
compared with RC. The planned comparison was TMT versus RC plus pelvic
lymphadenectomy as first-line treatment. The primary outcome was overall survival
(OS) and secondary outcomes were salvage cystectomy and cancer-specific survival
and progression-free survival. A search strategy was designed for MEDLINE,
CENTRAL, Embase, and LILACS. We saturated information with conference abstracts,
in progress clinical trials, literature published in non-indexed journals, and
other sources of gray literature. Standardized tools assessed the risk of bias
independently. We performed the statistical analysis in R v3.4.1 and effect sizes
were reported in terms of hazard ratios (HR) and the corresponding 95% confidence
intervals (95%CI). Accordingly, we used a random effect model due to the
statistical heterogeneity found in included studies. RESULTS: We found 2682
records with the search strategies and, finally, 11 studies were included in the
quantitative analysis. The summary HR for OS was 1.06 95%CI (0.85-1.31) I2 = 77%,
showing no statistical difference. Regarding cancer-specific survival, the
summary HR was 1.23 95%CI (1.04-1.46) I2 = 14%. On the other side, for the
progression-free survival, the summary HR was 1.11 95%CI (0.63-1.95) I2 = 78%.
Only one study described HR for adverse events (1.37 95%CI 1.16-1.59).
CONCLUSION: We found no differences in overall survival and progression-free
survival between these two interventions. Nonetheless, we found that cancer
specific survival favored patients who received radical cystectomy.
PMID- 29943219
TI - Ablation energies for focal treatment of prostate cancer.
AB - CONTEXT: In recent years, focal therapy has emerged as a treatment option for a
selected group of men with localized prostate cancer. Cryotherapy and high
intensity focused ultrasound (HIFU) are the most investigated types of focal
treatment with other options currently under evaluation. OBJECTIVE: The objective
of the study was to give a comprehensive overview of six available focal
treatment options for prostate cancer with their rationale, delivery mechanism,
and outcomes. INFORMATION ACQUISITION: The SIU ICUD chapter on available Energies
to Treat Prostate Cancer was used as a guide to describe the different
technologies. For outcomes, a literature search was conducted using PubMed key
words including focal therapy, HIFU, cryotherapy, irreversible electroporation,
vascular-targeted photodynamic therapy, laser interstitial therapy,
radiofrequency ablation, microwave therapy, and their synonyms in MeSH terms.
CONCLUSION: Focal therapy appears to have encouraging outcomes on quality of life
and urinary and erectile function. For oncological outcomes, it is challenging to
fully interpret the outcomes due to heterogeneity in patient selection and short
term follow-up.
PMID- 29943220
TI - Beyond transrectal ultrasound-guided prostate biopsies: available techniques and
approaches.
AB - OBJECTIVES: Recent advances have led to the use of magnetic resonance imaging
(MRI) alone or with fusion to transrectal ultrasound (TRUS) images for guiding
biopsy of the prostate. Our group sought to develop consensus recommendations
regarding MRI-guided prostate biopsy based on currently available literature and
expert opinion. METHODS: The published literature on the subject of MRI-guided
prostate biopsy was reviewed using standard search terms and synthesized and
analyzed by four different subgroups from among the authors. The literature was
grouped into four categories-MRI-guided biopsy platforms, robotic MRI-TRUS fusion
biopsy, template mapping biopsy and transrectal MRI-TRUS fusion biopsy. Consensus
recommendations were developed using the Oxford Center for Evidence Based
Medicine criteria. RESULTS: There is limited high level evidence available on the
subject of MRI-guided prostate biopsy. MRI guidance with or without TRUS fusion
can lead to fewer unnecessary biopsies, help identify high-risk (Gleason >= 3 +
4) cancers that might have been missed on standard TRUS biopsy and identify
cancers in the anterior prostate. There is no apparent significant difference
between MRI biopsy platforms. Template mapping biopsy is perhaps the most
accurate method of assessing volume and grade of tumor but is accompanied by
higher incidence of side effects compared to TRUS biopsy. CONCLUSIONS: Magnetic
resonance imaging-guided biopsies are feasible and better than traditional
ultrasound-guided biopsies for detecting high-risk prostate cancer and anterior
lesions. Judicious use of MRI-guided biopsy could enhance diagnosis of clinically
significant prostate cancer while limiting diagnosis of insignificant cancer.
PMID- 29943222
TI - Introduction to State-of-the-Art Multidimensional Time-Resolved Spectroscopy
Methods.
AB - The field of multidimensional laser spectroscopy comprises a variety of highly
developed state-of-the-art methods, which exhibit broad prospects for
applications in several areas of natural, material, and even medical sciences.
This collection summarizes the main achievements from this area and gives basic
introductory insight into what is currently possible with such methods. In the
present introductory contribution, we briefly outline the general concept behind
multidimensional laser spectroscopy, for instance by highlighting the often
employed analogy between multidimensional laser spectroscopy and NMR methods. Our
initial introduction is followed by an overview of the most important and widely
used multidimensional spectroscopies' classification. Special emphasis is placed
on how the contributing spectral region defines a natural way of grouping the
techniques in terms of their information content. On this basis, we introduce the
most important graphical ways in which multidimensional data is generally
visualized. This is done by comparing specifically temporal and spectra axes that
make up each single multidimensional data plot. Several central experimental
methods that are common to the various techniques reviewed in this collection are
addressed in the perspective of recent developments and their impact on the
field. These methods include, for example, heterodyne/homodyne detection, fast
scanning, spatial light modulation, and sparse sampling methods. Importantly, we
address the central and fundamental questions where multidimensional ultrafast
spectroscopy can be used to help understanding chemical dynamics and
intermolecular interactions. Finally, we briefly pinpoint what we believe are the
main open questions and what will be the future directions for technical
developments and promotion of scientific understanding that multidimensional
spectroscopy can provide for chemistry, physics, and life sciences.
PMID- 29943221
TI - Newborn screening for homocystinurias: recent recommendations versus current
practice.
AB - PURPOSE: To assess how the current practice of newborn screening (NBS) for
homocystinurias compares with published recommendations. METHODS: Twenty-two of
32 NBS programmes from 18 countries screened for at least one form of
homocystinuria. Centres provided pseudonymised NBS data from patients with
cystathionine beta-synthase deficiency (CBSD, n = 19), methionine
adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation
disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including
methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and
decision limits were converted to multiples of the median (MoM) to allow
comparison between centres. RESULTS: NBS programmes, algorithms and decision
limits varied considerably. Only nine centres used the recommended second-tier
marker total homocysteine (tHcy). The median decision limits of all centres were
>= 2.35 for high and <= 0.44 MoM for low methionine, >= 1.95 for high and <= 0.47
MoM for low methionine/phenylalanine, >= 2.54 for high propionylcarnitine and >=
2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had
a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD
and cRMD, respectively, but failed to detect six individuals with cRMD. To
enhance sensitivity and decrease second-tier testing costs, we further adapted
these decision limits using the data of 15,000 healthy newborns. CONCLUSIONS: Due
to the favourable outcome of early treated patients, NBS for homocystinurias is
recommended. To improve NBS, decision limits should be revised considering the
population median. Relevant markers should be combined; use of the postanalytical
tools offered by the CLIR project (Collaborative Laboratory Integrated Reports,
which considers, e.g. birth weight and gestational age) is recommended. tHcy and
methylmalonic acid should be implemented as second-tier markers.
PMID- 29943224
TI - Comparing the use of open and closed questions for Web-based measures of the
continued-influence effect.
AB - Open-ended questions, in which participants write or type their responses, are
used in many areas of the behavioral sciences. Although effective in the lab,
they are relatively untested in online experiments, and the quality of responses
is largely unexplored. Closed-ended questions are easier to use online because
they generally require only single key- or mouse-press responses and are less
cognitively demanding, but they can bias the responses. We compared the data
quality obtained using open and closed response formats using the continued
influence effect (CIE), in which participants read a series of statements about
an unfolding event, one of which is unambiguously corrected later. Participants
typically continue to refer to the corrected misinformation when making
inferential statements about the event. We implemented this basic procedure
online (Exp. 1A, n = 78), comparing standard open-ended responses to an
alternative procedure using closed-ended responses (Exp. 1B, n = 75). Finally, we
replicated these findings in a larger preregistered study (Exps. 2A and 2B, n =
323). We observed the CIE in all conditions: Participants continued to refer to
the misinformation following a correction, and their references to the target
misinformation were broadly similar in number across open- and closed-ended
questions. We found that participants' open-ended responses were relatively
detailed (including an average of 75 characters for inference questions), and
almost all responses attempted to address the question. The responses were
faster, however, for closed-ended questions. Overall, we suggest that with
caution it may be possible to use either method for gathering CIE data.
PMID- 29943223
TI - Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates
angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.
AB - Endoplasmic reticulum stress (ERS) is involved in the development of abdominal
aortic aneurysm (AAA). Since bioactive peptide intermedin (IMD)1-53 protects
against AAA formation, here we investigated whether IMD1-53 attenuates AAA by
inhibiting ERS. AAA model was induced by angiotensin II (AngII) in ApoE KO mouse
background. AngII-treated mouse aortas showed increased ERS gene transcription of
caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating
transcription factor 4(ATF4).The protein level of ERS marker glucose regulated
protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up
regulated by AngII. Increased ERS levels were accompanied by severe VSMC
apoptosis in human AAA aorta. In vivo administration of IMD1-53 greatly reduced
AngII-induced AAA and abrogated the activation of ERS. To determine whether IMD
inhibited AAA by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl
butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly
reduced the incidence of AAA and AAA-related pathological disorders. In vitro,
AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis.
IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was
abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of
adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in
ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect
of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect
against AAA formation by inhibiting ERS via activating AMPK phosphorylation.
PMID- 29943225
TI - Is systematic nasogastric decompression after pancreaticoduodenectomy really
necessary?
AB - BACKGROUND: Since the spread of enhanced recovery programs, early withdrawal of
the nasogastric tube (NGT) is recommended after pancreaticoduodenectomy (PD),
although few data on the safety of this practice are available. The aim of the
present study was to evaluate the absence of nasogastric decompression after PD
on postoperative outcome. STUDY DESIGN: All consecutive patients undergoing PD
between January 2014 and December 2015 at a single center were retrospectively
analyzed. Since May 2015, all operated patients had the NGT removed immediately
after the procedure (NGT- group) and were compared to patients operated before
this practice (NGT+ group), who had the NGT maintained until at least
postoperative day 3. RESULTS: During the study period, 139 patients underwent PD,
of whom 40 (29%) were in the NGT- group and 99 (71%) were in the NGT+ group. The
length of hospital stay (LOS) and rate of postoperative complications of grade 2
or higher according to the Clavien-Dindo grading system were significantly higher
in the NGT+ group [14 (11-25) vs. 10 (8-14.2), P = 0.005 and 82.8 vs. 40%, P <
0.001, respectively]. Incidence and severity of delayed gastric emptying (DGE)
grade B-C were also higher in the NGT+ group (45.5 vs. 7.5%, P < 0.001). There
was no difference between the two groups concerning the 90-day postoperative
mortality (P = 0.18). CONCLUSION: The absence of systematic nasogastric
decompression after PD might reduce postoperative complications, DGE, and LOS.
These encouraging results deserve to be confirmed by a prospective randomized
study (NCT: 02594956).
PMID- 29943226
TI - A radiation-free mixed-reality training environment and assessment concept for C
arm-based surgery.
AB - PURPOSE: The discrepancy of continuously decreasing opportunities for clinical
training and assessment and the increasing complexity of interventions in surgery
has led to the development of different training and assessment options like
anatomical models, computer-based simulators or cadaver trainings. However,
trainees, following training, assessment and ultimately performing patient
treatment, still face a steep learning curve. METHODS: To address this problem
for C-arm-based surgery, we introduce a realistic radiation-free simulation
system that combines patient-based 3D printed anatomy and simulated X-ray imaging
using a physical C-arm. To explore the fidelity and usefulness of the proposed
mixed-reality system for training and assessment, we conducted a user study with
six surgical experts performing a facet joint injection on the simulator.
RESULTS: In a technical evaluation, we show that our system simulates X-ray
images accurately with an RMSE of 1.85 mm compared to real X-ray imaging. The
participants expressed agreement with the overall realism of the simulation, the
usefulness of the system for assessment and strong agreement with the usefulness
of such a mixed-reality system for training of novices and experts. In a
quantitative analysis, we furthermore evaluated the suitability of the system for
the assessment of surgical skills and gather preliminary evidence for validity.
CONCLUSION: The proposed mixed-reality simulation system facilitates a transition
to C-arm-based surgery and has the potential to complement or even replace large
parts of cadaver training, to provide a safe assessment environment and to reduce
the risk for errors when proceeding to patient treatment. We propose an
assessment concept and outline the steps necessary to expand the system into a
test instrument that provides reliable and justified assessments scores
indicative of surgical proficiency with sufficient evidence for validity.
PMID- 29943228
TI - [S1 guidelines on malignant hyperthermia : Update 2018].
AB - The prevalence of malignant hyperthermia (MH) in Germany is 1:2000-1:3000 and
therefore more common than previously assumed, so that anesthesia personnel will
more often be confronted with susceptible patients in the clinical setting. After
the initial treatment with 2.5 mg/kg body weight dantrolene, further therapy
using up to 10 mg/body weight dantrolene can be indicated for 24 h. Under these
circumstances it is important to have a sufficient amount of water available for
injection purposes. For outpatient anesthesia a stockage of dantrolene is not
necessary as long as the use of MH trigger substances in general is strictly
avoided. The introduction of Ryanodex(r) (Eagle Pharmaceuticals, Woodcliff Lake,
NJ, USA), a preparation of dantrolene with clearly improved pharmacological
properties, in the clinical practice has not yet been realized in Germany.
PMID- 29943229
TI - Is Braak staging valid for all types of Parkinson's disease?
AB - Braak et al. proposed that cases with Lewy pathology in the peripheral nervous
sytem, spinal cord and brain stem are prodromal Parkinson's disease (PD),
suggesting a hypothesized progression of PD pathology. However, the putative
potential of peripheral alpha-synuclein to promote brain pathology has been
questioned recently. The Braak staging is a matter of vigorous debate, since <
100% of cases with Lewy pathology fitting the proposed PD staging scheme;
however, most studies assessing typical PD cases show that the vast majority (80
100%) fit the Braak staging scheme. Incidental Lewy body disease and PD can show
Lewy pathology in substantia nigra or other brain areas without involvement of
dorsal motor nucleus of the vagus nerve. The Braak staging system is valid for PD
patients with young onset, long duration with motor symptoms, but not for others,
e.g., late onset and rapid course PD. The validity of Braak staging and its
relationship to various subtypes of PD warrants further studies.
PMID- 29943227
TI - Health Literacy Among a Formerly Incarcerated Population Using Data from the
Transitions Clinic Network.
AB - Health literacy is increasingly understood to be a mediator of chronic disease
self-management and health care utilization. However, there has been very little
research examining health literacy among incarcerated persons. This study aimed
to describe the health literacy and relevant patient characteristics in a
recently incarcerated primary care patient population in 12 communities in 6
states and Puerto Rico. Baseline data were collected from 751 individuals through
the national Transitions Clinic Network (TCN), a model which utilizes a community
health worker (CHW) with a previous history of incarceration to engage previously
incarcerated people with chronic medical diseases in medical care upon release.
Participants in this study completed study measures during or shortly after their
first medical visit in the TCN. Data included demographics, health-related survey
responses, and a measure of health literacy, The Newest Vital Sign (NVS).
Bivariate and linear regression models were fit to explore associations among
health literacy and the time from release to first clinic appointment, number of
emergency room visits before first clinic appointment and confidence in adhering
to medication. Our study found that almost 60% of the sample had inadequate
health literacy. Inadequate health literacy was associated with decreased
confidence in taking medications following release and an increased likelihood of
visiting the emergency department prior to primary care. Early engagement may
improve health risks for this population of individuals that is at high risk of
death, acute care utilization, and hospitalization following release.
PMID- 29943230
TI - Handgrip Strength and Health in Aging Adults.
AB - Handgrip strength (HGS) is often used as an indicator of overall muscle strength
for aging adults, and low HGS is associated with a variety of poor health
outcomes including chronic morbidities, functional disabilities, and all-cause
mortality. As public health initiatives and programs target the preservation of
muscle strength for aging adults, it is important to understand how HGS factors
into the disabling process and the sequence of health events that connect low HGS
with premature mortality. Such information will help to inform interventions
designed to slow the disabling process and improve health outcomes for those at
risk for muscle weakness. Further, unraveling the disabling process and
identifying the role of weakness throughout the life course will help to
facilitate the adoption of HGS measurements into clinical practice for healthcare
providers and their patients. The purposes of this article were to (1) highlight
evidence demonstrating the associations between HGS and clinically relevant
health outcomes, (2) provide directions for future research in HGS and health,
and (3) propose a sequence of health-related events that may better explain the
role of muscle weakness in the disabling process.
PMID- 29943231
TI - The Relationship Between Training Load and Injury in Athletes: A Systematic
Review.
AB - BACKGROUND: The relationship between training load and musculoskeletal injury is
a rapidly advancing area of research in need of an updated systematic review.
OBJECTIVE: This systematic review examined the evidence for the relationship
between training load and musculoskeletal injury risk in athlete, military, and
first responder (i.e. law enforcement, firefighting, rescue service) populations.
METHODS: The CINAHL, EMBASE, MEDLINE, SportDISCUS, and SCOPUS databases were
searched using a comprehensive strategy. Studies published prior to July 2017
were included if they prospectively examined the relationship between training
load and injury risk. Study quality was assessed using the Newcastle-Ottawa
Quality Assessment Scale (NOS) and Oxford Centre for Evidence-Based Medicine
levels of evidence. A narrative synthesis of findings was conducted. RESULTS: A
total of 2047 articles were examined for potential inclusion. Forty-six met the
inclusion criteria and 11 known to the authors but not found in the search were
added, for a total of 57 articles. Overall, 47 studies had at least partially
statistically significant results, demonstrating a relationship between training
load and injury risk. Included articles were rated as poor (n = 15), fair (n =
6), and good (n = 36) based on NOS score. Articles assessed as 'good' were
considered level 2b evidence on the Oxford Centre for Evidence-Based Medicine
Model, and articles assessed as 'fair' or 'poor' were considered level 4
evidence. CONCLUSIONS: Our results demonstrate that the existence of a
relationship between training load and injury continues to be well supported in
the literature and is strongest for subjective internal training load. The
directionality of this relationship appears to depend on the type and timeframe
of load measured.
PMID- 29943232
TI - Prognostic benefit of acute heart failure associated with atherosclerosis: the
importance of prehospital medication in patients with severely decompensated
acute heart failure.
AB - Atherosclerotic diseases sometimes contribute to acute heart failure (AHF). The
aim of the present study is to elucidate the prognostic impact of AHF with
atherosclerosis. A total of 1226 AHF patients admitted to the intensive care unit
were analyzed. AHF associated with atherosclerosis was defined by the etiology:
atherosclerosis-AHF group (n = 708) (patients whose etiologies were ischemic
heart disease or hypertensive heart disease) or AHF not associated with
atherosclerosis (non-atherosclerosis-AHF) group (n = 518). Kaplan-Meier curves
showed that the survival rate of the atherosclerosis-AHF group was significantly
better than that of the non-atherosclerosis-AHF group within 730 days of follow
up. Regarding pre-hospital medications, atherosclerosis-AHF patients were more
likely to be administered nitroglycerin (20.3 vs. 13.7%, p = 0.003), nicorandil
(18.8 vs. 7.5%, p < 0.001), angiotensin-converting enzyme inhibitor (ACE-I) or
angiotensin II receptor blocker (ARB) (46.5 vs. 38.6%, p = 0.006), beta-blocker
(33.2 vs. 26.6%, p = 0.014) and statin (30.1 vs. 22.4%, p = 0.003) because of a
previous coronary event or atherosclerotic diseases. In sub-group analysis of
medication including administered >= 3 drugs within 5 medications and ACE-I/ARB,
atherosclerosis-AHF significantly decreased the rate of all-cause death within
180 days (hazard ratio (HR) 0.215, 95% CI 0.078-0.593 and HR 0.395, 95% CI 0.244
0.641, respectively) with a significant interaction (p value for interaction
0.022 and 0.005, respectively). Kaplan-Meier curves showed that the 180-days
survival rate of the atherosclerosis-AHF group with ACE-I/ARB and >= 3 drugs were
significantly better than other groups. The AHF patients associated with
atherosclerosis lead to be a good long-term outcome. A relationship may exist
between efficient treatment including ACE-Is before admission and a good outcome
in mid-term.
PMID- 29943233
TI - Osteogenic differentiation of encapsulated rat mesenchymal stem cells inside a
rotating microgravity bioreactor: in vitro and in vivo evaluation.
AB - The objective of this study is to evaluate the in vitro and in vivo osteogenic
potential of rat bone marrow mesenchymal stem cells (BM-MSCs) using
chitosan/hydroxyapatite (C/HAp) microbeads as encapsulation matrix under
osteoinductive medium and dynamic culture conditions. The degradation
characteristics of C/HAp microbeads were evaluated under in vitro and in vivo
conditions for 180 days. BM-MSCs were encapsulated in C/HAp microbeads with > 85%
viability, and were cultured in a slow turning lateral vessel-type rotating
bioreactor simulating microgravity conditions for 28 days, under the effect of
osteogenic inducers. MTT assay showed that the metabolic activity of encapsulated
cells was preserved > 80% after a week. In vitro experiments confirmed that the
encapsulated BM-MSCs differentiated into osteoblastic cells, formed bone-like
tissue under osteogenic microgravity bioreactor conditions. Preliminary in vivo
study indicated C/HAp microbeads containing BM-MSCs were able to repair the
surgically-created small bone defects in the rat femur. BM-MSCs-C/HAp composite
microbeads may have potential for modular bone regeneration.
PMID- 29943235
TI - Identification of Abnormal 51 CTA/CTG Expansion as Probably the Shortest
Pathogenic Allele for Spinocerebellar Ataxia-8 in China.
PMID- 29943234
TI - Update on the Gastrointestinal Microbiome in Systemic Sclerosis.
AB - PURPOSE OF REVIEW: Accumulating evidence suggests that gut microbiota affect the
development and function of the immune system and may play a role in the
pathogenesis of autoimmune diseases. The purpose of this review is to summarize
recent studies reporting gastrointestinal microbiota aberrations associated with
the systemic sclerosis disease state. RECENT FINDINGS: The studies described
herein have identified common changes in gut microbial composition. Specifically,
patients with SSc have decreased abundance of beneficial commensal genera (e.g.,
Faecalibacterium, Clostridium, and Bacteroides) and increased abundance of
pathobiont genera (e.g., Fusobacterium, Prevotella, Erwinia). In addition, some
studies have linked specific genera with the severity of gastrointestinal
symptoms in systemic sclerosis. More research is needed to further characterize
the gastrointestinal microbiota in systemic sclerosis and understand how
microbiota perturbations can affect inflammation, fibrosis, and clinical
outcomes. Interventional studies aimed at addressing/correcting these
perturbations, either through dietary modification, pro/pre-biotic
supplementation, or fecal transplantation, may lead to improved outcomes for
patients with systemic sclerosis.
PMID- 29943236
TI - Systems-Based Interactome Analysis for the Hematopoiesis Effect of Angelicae
Sinensis Radix: Regulated Network of Cell Proliferation towards Hemopoiesis.
AB - OBJECTIVE: To explore the molecular-level mechanism on the hematopoiesis effect
of Angelicae Sinensis Radix (ASR) with systems-based interactome analysis.
METHODS: This systems-based interactome analysis was designed to enforce the
workflow of "ASR (herb)->compound->target protein->internal protein actions
>ending regulated protein for hematopoiesis". This workflow was deployed with
restrictions on regulated proteins expresses in bone marrow and anemia disease
and futher validated with experiments. RESULTS: The hematopoiesis mechanism of
ASR might be accomplished through regulating pathways of cell proliferation
towards hemopoiesis with cross-talking agents of spleen tyrosine kinase (SYK),
Janus kinase 2 (JAK2), and interleukin-2-inducible T-cell kinase (ITK). The
hematopoietic function of ASR was also validated by colony-forming assay
performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were
activated. CONCLUSION: This study provides a new approach to systematically study
and predict the therapeutic mechanism for ASR based on interactome analysis
towards biological process with experimental validations.
PMID- 29943237
TI - Antidepressants and recurrence of depression in the postpartum period.
AB - To examine postpartum recurrence rates of depression comparing women receiving
antidepressant treatment to women not being treated with psychotropic medication.
This was a prospective study of 130 women with major depressive disorder (MDD)
who attended a tertiary care perinatal clinic during and after pregnancy.
Depression recurrence was defined as a score of 13 or more on the Edinburgh
Postnatal Depression Scale (EPDS) or a score of greater than 13 on the Hamilton
Depression Rating Scale (HDRS). Over half of women (56.9%) were not receiving
medication during pregnancy to treat their mood disorder, with the rate of
medication use increasing over the 1-year postpartum period. When comparing women
being treated with antidepressant medication (monotherapy or combination therapy)
to women receiving no psychotropic medication, no significant differences in
recurrence rates were observed during the postpartum period. However, we did
observe that the occurrence of depression in our sample fluctuated between rates
comparable to general population estimates to rates that were at times more than
twofold higher, regardless of treatment with antidepressant medication. The
findings of this study align with research which suggests that the postpartum
period is a particularly vulnerable time for recurrence of depression. Moreover,
our results suggest that this remains the case regardless of antidepressant
treatment.
PMID- 29943241
TI - [Modern genetic counselling : Practical aspects exemplified by hypertrophic
cardiomyopathy].
AB - Genetic counselling and subsequent molecular genetic testing should be performed
in patients when an inherited monogenic form of heart disease is suspected. For
the individual patient as well as for the (possibly asymptomatic) relatives,
molecular diagnostics is important for an early diagnosis, (preventive) therapy
and prognosis assessment. Using the example of hypertrophic cardiomyopathy (HCM),
the most common monogenic form of structural heart disease, essential aspects of
modern genetic counselling are elucidated. Specific examples of one case with a
classical form of hypertrophic obstructive cardiomyopathy and one case of
congenital HCM with Noonan's syndrome are discussed.
PMID- 29943240
TI - [Genetic testing to prevent sudden cardiac death].
AB - Successfully incorporating genetic testing into clinical practice to prevent
sudden cardiac death (SCD) requires (1) appropriate recognition of an inherited
cardiovascular condition, (2) identification of appropriate family members at
risk and for genetic testing, (3) selection of the appropriate genetic test and
information about the expected diagnostic yield, (4) understanding the complexity
of result interpretation and distinct handling of incidental findings and (5)
providing effective communication and medical advice regarding the genetic and
medical results and implications to the patient and his family. Molecular autopsy
in SCD victims will be of future importance to determine the cause of death.
Interdisciplinary patient care should be provided in specialized centers with a
high level of cardiogenetic expertise and is recommended to provide precise and
individualized patient management.
PMID- 29943239
TI - The effects of transcranial alternating current stimulation (tACS) at individual
alpha peak frequency (iAPF) on motor cortex excitability in young and elderly
adults.
AB - Transcranial alternating current stimulation (tACS) can modulate brain
oscillations, cortical excitability and behaviour. In aging, the decrease in EEG
alpha activity (8-12 Hz) in the parieto-occipital and mu rhythm in the motor
cortex are correlated with the decline in cognitive and motor functions,
respectively. Increasing alpha activity using tACS might therefore improve
cognitive and motor function in the elderly. The present study explored the
influence of tACS on cortical excitability in young and old healthy adults. We
applied tACS at individual alpha peak frequency for 10 min (1.5 mA) to the left
motor cortex. Transcranial magnetic stimulation was used to assess the changes in
cortical excitability as measured by motor-evoked potentials at rest, before and
after stimulation. TACS increased cortical excitability in both groups. However,
our results also suggest that the mechanism behind the effects was different, as
we observed an increase and decrease in intracortical inhibition in the old group
and young group, respectively. Our results indicate that both groups profited
similarly from the stimulation. There was no indication that tACS was more
effective in conditions of low alpha power, that is, in the elderly.
PMID- 29943242
TI - Accurate Coil Positioning is Important for Single and Paired Pulse TMS on the
Subject Level.
AB - Function-guided navigation is commonly used when assessing cortical excitability
using transcranial magnetic stimulation (TMS). However, the required accuracy,
stability and the effect of a change in coil positioning are not entirely known.
This study investigates the accuracy of function-guided navigation for
determining the hotspot. Furthermore, it evaluates the effect of a change in coil
location on the single and paired pulse excitability measures: motor evoked
potential (MEP) amplitude, TMS evoked potential (TEP) and long intracortical
inhibition (LICI), and of a change in coil orientation on LICI. Eight healthy
subjects participated in the single pulse study, and ten in the paired pulse
study. A robot-guided navigation system was used to ensure accurate and stable
coil positioning at the motor hotspot as determined using function-guided
navigation. In addition, we targeted four locations at 2 mm and four at 5 mm
distance around the initially defined hotspot, and we increased and decreased the
coil orientation by 10 degrees . In none of the subjects, the largest MEP
amplitudes were evoked at the originally determined hotspot, resulting in a poor
accuracy of function-guided navigation. At the group level, a change in coil
location had no significant effect on the MEP amplitude, TEP, or LICI, and a
change in coil orientation did not significantly affected LICI. However, at the
subject level significant effects on MEP amplitude, TEP, and LICI were found for
changes in coil location or orientation, although absolute differences were
relatively small and did not show a consistent pattern. This study indicates that
a high accuracy in coil positioning is especially required to measure cortical
excitability reliably in individual subjects using single or paired pulse TMS.
PMID- 29943243
TI - Calibration and application of the Chemcatcher(r) passive sampler for monitoring
acidic herbicides in the River Exe, UK catchment.
AB - Acidic herbicides are used to control broad-leaved weeds. They are stable, water
soluble, and with low binding to soil are found frequently in surface waters,
often at concentrations above the EU Drinking Water Directive limit of 0.10 MUg L
1. This presents a problem when such waters are abstracted for potable supplies.
Understanding their sources, transport and fate in river catchments is important.
We developed a new Chemcatcher(r) passive sampler, comprising a 3M EmporeTM anion
exchange disk overlaid with a polyethersulphone membrane, for monitoring acidic
herbicides (2,4-D, dicamba, dichlorprop, fluroxypyr, MCPA, MCPB, mecoprop,
tricolpyr). Sampler uptake rates (Rs = 0.044-0.113 L day-1) were measured in the
laboratory. Two field trials using the Chemcatcher(r) were undertaken in the
River Exe catchment, UK. Time-weighted average (TWA) concentrations of the
herbicides obtained using the Chemcatcher(r) were compared with concentrations
measured in spot samples of water. The two techniques gave complimentary
monitoring data, with the samplers being able to measure stochastic inputs of
MCPA and mecoprop occurring in field trial 1. Chemcatcher(r) detected a large
input of MCPA not found by spot sampling during field trial 2. Devices also
detected other pesticides and pharmaceuticals with acidic properties. Information
obtained using the Chemcatcher(r) can be used to develop improved risk
assessments and catchment management plans and to assess the effectiveness of any
mitigation and remediation strategies.
PMID- 29943244
TI - Fodder radish seed cake biochar for soil amendment.
AB - In this work, fodder radish seed cake (FRSC) was pyrolyzed in a rotary kiln
reactor at 0, 3, and 6 rpm, at final temperature of 500 degrees C. Maximum
biochar yield was observed at 0 rpm (~ 26 wt.%). Increase of the rotary speed
decreased the volatile matter content and increased the ash content of the
biochars. Biochars exhibited alkaline pH (~ 9.0), low electrical conductivity (<
105.6 dS m-1), and high cation exchange capacity (69 to 78 cmolc kg-1), as well
as high nitrogen contents (~ 80 g kg-1). FTIR analysis presented biochars with
similar spectra, with carboxyl and carbonyl groups within the structure, along
with aromatic rings and nitrogen containing functions (amides). Biochar
incubation experiments in an acrisol at different biochar doses (5 g L-1 soil to
40 g L-1 soil) were performed in order to evaluate changes in soil fertility
parameters caused by FRSC biochar application. Results indicated that most of
macro (N, P, K, Ca, Mg) and micronutrients (S, Cu, Zn, Mn, B, Na) increased with
increase of the dosage, along with the decrease in Al and H+ Al contents. An
increase in pH (from 4.25 to 5.33) was also observed, in electric conductivity
(from 30.0 to 45.7 dS m-1), and a decrease in soil real density (from 3.67 to
2.99 kg L-1) at the dosage of 40 g char L-1 soil.
PMID- 29943245
TI - Integrated adsorption-solar photocatalytic membrane reactor for degradation of
hazardous Congo red using Fe-doped ZnO and Fe-doped ZnO/rGO nanocomposites.
AB - In this work, synergistic effect of solar photocatalysis integrated with
adsorption process towards the degradation of Congo red (CR) was investigated via
two different approaches using a photocatalytic membrane reactor. In the first
approach, sequential treatments were conducted through the adsorption by graphene
oxide (GO) and then followed by photocatalytic oxidation using Fe-doped ZnO
nanocomposites (NCs). In the second approach, however, CR solution was treated by
photocatalytic oxidation using Fe-doped ZnO/rGO NCs. These nanocomposites were
synthesized by a sol-gel method. The NCs were characterized by X-ray diffraction
(XRD), photoluminescence (PL), Fourier transmission infrared (FTIR), ultraviolet
visible (UV-vis) spectroscopy, and field emission scanning electron microscopy
(FESEM). It was observed that Fe-doped ZnO could enhance the photoactivity of ZnO
under solar light. When Fe-doped ZnO were decorated on GO sheets, however, this
provided a surface enhancement for adsorption of organic pollutants. The
photocatalytic performances using both approaches were evaluated based on the
degradation of CR molecules in aqueous solution under solar irradiation.
Nanofiltration (NF) performance in terms of CR residual removal from water and
their fouling behavior during post-separation of photocatalysts was studied.
Serious flux declined and thicker fouling layer on membrane were found in
photocatalytic membrane reactor using Fe-doped ZnO/rGO NCs which could be
attributed to the stronger pi-pi interaction between rGO and CR solution.
PMID- 29943246
TI - Metal release and sequestration from black slate mediated by a laccase of
Schizophyllum commune.
AB - Schizophyllum commune is a filamentous basidiomycete which can degrade complex
organic macromolecules like lignin by the secretion of a large repertoire of
enzymes. One of these white rot enzymes, laccase, exhibits a broad substrate
specificity and is able to oxidize a variety of substances including carbonaceous
rocks. To investigate the role of laccase in bioweathering, laccase gene lcc2 was
overexpressed, and the influence on weathering of black slate, originating from a
former alum mine in Schmiedefeld, Germany, was examined. The metal release from
the rock material was enhanced, associated with a partial metal accumulation into
the mycelium. A sequestration of metals could be shown with fluorescent staining
methods, and an accumulation of Zn, Cd, and Pb was visualized in different cell
organelles. Additionally, we could show an increased metal resistance of the
laccase overexpressing strain.
PMID- 29943247
TI - Gibberellins application timing modulates growth, physiology, and quality
characteristics of two onion (Allium cepa L.) cultivars.
AB - Lack of scientific literature exists regarding the effects of gibberellic acid
(GA3) application timings on various phenological and physiological aspects of
seed crop of locally available onion cultivars. Therefore, current study was
planned in Vegetable Research Area, University of Agriculture, Faisalabad to
optimize the growth stage for GA3 application on seed production in two local
onion cultivars (Phulkara and Dark Red) during 2013 and 2014. Application timings
of gibberellins at 100 mg/L of H2O were as (G1) control (no spray), (G2) foliar
application at 2-3 leaf stage, (G3) foliar application at 6-7 leaf stage, and
(G4) foliar application at the time of flowering. Data on average of both years
showed that tallest plants (66.15 cm) and maximum number of leaves per plant
(84.56) were noted in cv. Phulkara when GA3 was applied at 2-3 leaf stage.
Minimum number of days to initiate flowering (47.92) and maximum number of umbels
per plant (15.45) were noted with GA3 application at 6-7 leaf stage in Phulkara
and Dark Red, respectively. The highest seed yield per umbel (2.94 g) was
recorded in cv. Dark Red when GA3 sprayed at 6-7 leaf stage, while GA3
application at the time of flowering in the cv. Phulkara produced seeds with
highest seedling vigor index (586.79). Overall, it appears that seed yield and
quality characters were promoted by the application of GA3 at different growth
stages and could be valuable for seed production of onion.
PMID- 29943248
TI - Levels, distribution, and ecological risk of organochlorines in red mullet
(Mullus barbatus) and annular sea bream (Diplodus annularis) from the Gulf of
Izmir, Eastern Aegean, in 2009-2012.
AB - Organochlorine (OCs) concentrations were measured in two fish species, Mullus
barbatus and Diplodus annularis, collected from Izmir Gulf during 2009-2012 in
order to explain the status of these contaminants in edible fish. No data is
available on the levels of organochlorines in marine organism from Izmir Gulf. In
both fish species from the study area, Aroclors were determined in higher
concentrations than organochlorine pesticides (OCPs). Maximum concentrations of
OCPs and PCBs measured in the edible part of D. annularis were 45-165 and 530
1591 ng g-1 lipid weight (lw), respectively. DDTs (sum of DDT and metabolites)
and cyclodienes ranged from 4-56 to 16-110 ng g-1 lw, respectively. The levels of
DDTs measured in the present study were generally comparable or lower than those
found in studies from other Mediterranean and non-Mediterranean regions. The
potential risks for fish consumers were assessed. Although the estimated daily
intake (EDI) for DDTs, heptachlor, and drins through the sampled fish species by
Izmir inhabitants was quite lower than the ADI (acceptable daily intake)
established by the FAO/WHO, EDI for Aroclor 1254 was close to the ADI value of 20
ng g-1 recommended by the IPCS (2000).
PMID- 29943249
TI - Accuracy of data buoys for measurement of cyanobacteria, chlorophyll, and
turbidity in a large lake (Lake Erie, North America): implications for estimation
of cyanobacterial bloom parameters from water quality sonde measurements.
AB - Microcystin (MCY)-producing harmful cyanobacterial blooms (cHABs) are an annual
occurrence in Lake Erie, and buoys equipped with water quality sondes have been
deployed to help researchers and resource managers track cHABs. The objective of
this study was to determine how well water quality sondes attached to buoys
measure total algae and cyanobacterial biomass and water turbidity. Water samples
were collected next to two data buoys in western Lake Erie (near Gibraltar Island
and in the Sandusky subbasin) throughout summers 2015, 2016, and 2017 to
determine correlations between buoy sonde data and water sample data. MCY and
nutrient concentrations were also measured. Significant (P < 0.001) linear
relationships (R2 > 0.75) occurred between cyanobacteria buoy and water sample
data at the Gibraltar buoy, but not at the Sandusky buoy; however, the
coefficients at the Gibraltar buoy differed significantly across years. There was
a significant correlation between buoy and water sample total chlorophyll data at
both buoys, but the coefficient varied considerably between buoys and among
years. Total MCY concentrations at the Gibraltar buoy followed similar temporal
patterns as buoy and water sample cyanobacterial biomass data, and the ratio of
MCY to cyanobacteria-chlorophyll decreased with decreased ambient nitrate
concentrations. These results suggest that buoy data are difficult to compare
across time and space. Additionally, the inclusion of nitrate concentration data
can lead to more robust predictions on the relative toxicity of blooms. Overall,
deployed buoys with sondes that are routinely cleaned and calibrated can track
relative cyanobacteria abundance and be used as an early warning system for
potentially toxic blooms.
PMID- 29943251
TI - Oxidation of ethylenethiourea in water via ozone enhanced by UV-C: identification
of transformation products.
AB - Ethylenethiourea (ETU) is a toxic degradation product of one class of fungicide
which is largely employed in the world, the ethylenebisdithiocarbamates. In this
study, ETU was degraded by ozonation enhanced by UV-C light irradiation (O3/UV-C)
in aqueous medium. Degradation experiments were conducted at natural pH (6.8) and
neutral pH (7.0, buffered). ETU was promptly eliminated from the reactive medium
during ozonation in the presence and absence of light. Within the first few
minutes of reaction conducted in natural pH, the pH decreased quickly from 6.8 to
3.0. Results show that ETU mineralization occurs only in the reaction conducted
in neutral pH and that it takes place in a higher rate when enhanced by UV-C
irradiation. Main intermediates formed during the O3/UV-C experiments in
different conditions tested were also investigated and three different
degradation mechanisms were proposed considering the occurrence of direct and
indirect ozone reactions. At pH 7, ethylene urea (EU) was quickly generated and
degraded. Meanwhile, at natural pH, besides EU, other compounds originated from
the electrophilic attack of ozone to the sulfur atom present in the contaminant
molecule were also identified during reaction and EU was detected within 60 min
of reaction. Results showed that ozonation enhanced by UV-C promotes a faster
reaction than the same system in the absence of light, and investigation of the
toxicity is recommended.
PMID- 29943250
TI - Bio-concentration potential and associations of heavy metals in Amanita muscaria
(L.) Lam. from northern regions of Poland.
AB - Fruiting bodies of Amanita muscaria and topsoil beneath from six background areas
in northern regions of Poland were investigated for the concentration levels of
Ag, Al, Ba, Ca, Cd, Co, Cu, Fe, Hg, K, Mg, Mn, Na, Rb, Sr, and Zn. In addition,
the bioconcentration factors (BCF values) were studied for each of these metallic
elements. Similar to studies from other basidiomycetes, A. muscaria showed
species-specific affinities to some elements, resulting in their bioconcentration
in mycelium and fruiting bodies. This mushroom growing in soils with different
levels of the geogenic metallic elements (Ag, Al, Ba, Ca, Co, Cu, Fe, Hg, K, Mg,
Mn, Na, Rb, Sr, and Zn) showed signs of homeostatic accumulation in fruiting
bodies of several of these elements, while Cd appeared to be accumulated at a
rate dependent of the concentration level in the soil substrate. This species is
an efficient bio-concentrator of K, Mg, Cd, Cu, Hg, Rb, and Zn and hence also
contributes to the natural cycling of these metallic elements in forest
ecosystems.
PMID- 29943252
TI - Growth, physiological adaptation, and NHX gene expression analysis of Iris
halophila under salt stress.
AB - This study investigated the growth, physiological changes, and the transcript
levels of NHX1 gene of Iris halophila in response to low NaCl concentration (50
mM) and high NaCl concentration (150 mM). Our results showed that both 50 and 150
mM NaCl had no obvious negative effects on plant growth; what is more, low NaCl
concentration (50 mM) increased root length, root fresh weight, and the ratio of
root length to leaf length compared with the control group. The malondialdehyde
(MDA) contents in leaves and roots of I. halophila had no obvious difference as
compared with control. Proline levels of I. halophila exhibited basically an
enhancement under salt stress conditions. Particularly at 4 days, the proline
contents in leaves reached 1.85 to 2.31-fold higher and the contents in roots
reached 1.27 to 1.62-fold higher than that of control at 50 and 150 mM NaCl,
respectively. The contents of the soluble sugar in leaves and roots of I.
halophila under 150 mM NaCl at 7 days were 32.4 and 98.7% higher than that of
control, respectively. The increase rate of K+ contents with the increasing
concentration of salt was less than that of Na+ contents, but K+ contents in the
seedlings under NaCl stress was still higher than Na+ contents and the ratio of
K+ to Na+ was also greater than 1. The transcript levels of IhNHX1 in leaves of
I. halophila at 4 and 7 days under 150 mM NaCl were higher than that of control;
however, the transcript levels of IhNHX1 in roots had no significant difference
compared with the control under low and high salt stress at 1, 4, and 7 days.
Therefore, salt tolerance in I. halophila could be partially due to higher
proline, soluble sugar, and K+ accumulation.
PMID- 29943253
TI - Mercury, cadmium, and lead content in demersal sharks from the Macaronesian
islands.
AB - The overexploitation of shark and ray fishing as well as anthropogenic pollution
in the sea has led to a large decline in their population, and because sharks
occupy a high trophic position in the ecosystem, they could have high
concentrations of heavy metals such as Hg, Pb, and Cd. This study is based on
seven species of demersal sharks which were caught in the Macaronesian
archipelagos (Tenerife, Gran Canaria, and the Azores Archipelago). Hg and Pb
concentrations were found in the present study to be below those reported in
other comparative studies, with the highest reported values of Hg and Pb being
281,738 MUg/kg for Pb in Deania profundorum (Smith & Radcliffe, 1912) and 264,30
MUg/kg for Hg in Centrophorus uyato, Rafinesque, 1810. As for Cd, the values
found here are higher than those in the literature, the highest reported
concentration being 120.36 MUg/kg in Centrophorus squamosus (Bonnaterre, 1788).
PMID- 29943254
TI - Effects of Bacillus subtilis and nanohydroxyapatite on the metal accumulation and
microbial diversity of rapeseed (Brassica campestris L.) for the remediation of
cadmium-contaminated soil.
AB - This study investigated the effects of the co-application of Bacillus subtilis
and nanohydroxyapatite (NHAP) on plant growth, soil cadmium (Cd) dynamics, and
the microbiological characteristics (such as enzyme activity and bacterial
species richness) of the rhizosphere soil. Rapeseed was used as a model plant in
pot experiments. Different concentrations of B. subtilis and 0.5% NHAP were
applied alone and in combination to Cd-contaminated soil. The Cd contents in
soils and plants as well as the rhizospheric microorganism diversity were
assessed. The addition of B. subtilis or NHAP alone increased the soil Cd content
and decreased the plant Cd content, while their co-application more effectively
increased the soil and plant Cd contents than either treatment alone. B. subtilis
and NHAP reduced the plant Cd content by 43.15-57.04% compared with that in the
control. Rhizosphere community richness and bacterial diversity were
significantly increased after co-application of B. subtilis and NHAP. Co
application of B. subtilis and NHAP effectively promoted rapeseed growth and
improved Cd-contaminated soil remediation.
PMID- 29943255
TI - Hydrophilic modification and anti-fouling properties of PVDF membrane via in situ
nano-particle blending.
AB - Two hydrophilic poly-vinylidene fluoride (PVDF) ultrafiltration membranes were
prepared via in situ embedment of nanoparticles (NP), i.e., TiO2 and Al2O3,
respectively, and their anti-organic-fouling and anti-biofouling were
comprehensively investigated. Characterization of modified PVDF-NP membranes by
XRD and FTIR exhibited that nanoparticles were embedded successfully. Series of
fast filtration tests demonstrated that in contrary to virgin PVDF membrane, PVDF
NP membranes have high permeability and anti-organic-fouling ability by
decreasing the possibility of organic matters deposition and accumulation. Co
existed Ca2+ in feed solution deteriorated the organic fouling in virgin PVDF and
PVDF-NP membranes, which was mainly caused by gelation of macromolecular
foulants. PVDF-NP membranes were used to form MBR modules for domestic wastewater
treatment, and the long-term monitoring evidenced that hydrophilic modified
membranes achieved stably high COD and [Formula: see text] rejection
efficiencies, and better organic rejection capability than mAO process. PVDF-NP
membranes possessed consistently high anti-biofouling ability to maintain stable
membrane permeability.
PMID- 29943256
TI - Correction to: Deep Learning for Drug Design: an Artificial Intelligence Paradigm
for Drug Discovery in the Big Data Era.
AB - The name of the corresponding author should be 'Xiang-Qun Xie', rather than
'Xiang-Qun Sean Xie'.
PMID- 29943258
TI - ?
PMID- 29943259
TI - [The importance of breastfeeding for the infant].
AB - Breastmilk is natural nutrition for infants. In addition to nutrients, breast
milk contains a variety of immunomodulatory, anti-inflammatory and antimicrobial
substances that help to reduce short- and long-term morbidity risks and
positively influence the child's cognitive and psychomotor development. Studies
show that breastfed children are at a significantly lower risk for lower
respiratory tract infections, otitis media, and gastroenteritis compared with non
breastfed children. Also, the risk for sudden infant death syndrome is
significantly reduced by breastfeeding. Breastfeeding does not have an influence
on the risk of allergies, neither in the overall population nor in children with
a familial predisposition. However, breastfeeding promotes brain development,
especially of the white matter, and is associated with improved intelligence by
about 2 IQ points. Furthermore, studies show an inverse correlation between
breastfeeding and the subsequent risk for obesity, and there is evidence for a
risk reduction of type 2 diabetes mellitus. Breastfed infants can largely
regulate their food intake. This can have a positive effect on later eating
behavior and the risk for becoming overweight. In view of the positive health
effects of breastfeeding, it is recommended that infants be breast-fed
exclusively during the first few months of life and that complementary feeding
should be started at the earliest from the beginning of the 5th month and no
later than at the beginning of the 7th month. Complementary food should be
offered in a suitable form and with consideration of the signals of the child.
Overall, breastfeeding can make a significant contribution to promoting public
health and thereby to reducing healthcare costs.
PMID- 29943257
TI - Globus pharyngeus: a review of etiology, diagnostics, and treatment.
AB - Globus is a non-painful sensation of a lump or a foreign body in the throat, and
it frequently improves with eating. Although globus is a common symptom, only
little is known about the etiology, and the causes have remained controversial.
Previously, globus was labelled as a hysterical symptom. However, nowadays, the
research has been mainly focused on somatic causes and it is suspected that the
etiology is complex. Because of the unclear etiology, the diagnostics and
treatment are varying, predisposing patients to possible unnecessary
investigations. This review presents the current literature of globus: its
etiology, diagnostics, and treatment. In addition, a special aim is to discuss
the rational investigation methods in globus diagnostics and present a diagnostic
algorithm based on recent researches.
PMID- 29943260
TI - [Monitoring breastfeeding in Germany-the current need for action and
perspectives].
AB - Breastfeeding monitoring is understood to be the systematic assessment of
current, comprehensive and precise data on breastfeeding rates, breastfeeding
behaviour and relevant framework conditions at a national and regional level,
with the aim of optimal breastfeeding support. For this purpose, in 2009, the
National Breastfeeding Committee in Germany presented an integrative monitoring
concept that included different assessment instruments and assessment fields. The
hitherto fragmented implementation is still insufficient; in particular, the
implementation of longer-term and sustainable concepts within the structures of
the healthcare system is still lacking.To systematically collect breastfeeding
data, it is mandatory to integrate the different modules. Longitudinal data on
selected core breastfeeding indicators should be collected within the quality
assurance structures of perinatal medicine and within the regular school entrance
examinations, and be integrated into the health surveillance system. Detailed
epidemiological studies on breastfeeding and infant nutrition should be carried
out every 5 years, covering influencing factors from pregnancy until the end of
the first year of life. The monitoring of high-risk groups should take place with
systematic interventions within the institutionalized frameworks of "Early
Preventions" (local support systems offering assistance to parents and children)
and health authorities with social compensatory activities, with the immediate
transfer to of the results into practice.The integrative concept of breastfeeding
monitoring in Germany is in accordance with international criteria, tailored to
existing structures and experiences, and can be presented internationally.
Sufficient centralized resources are needed to coordinate and implement this
concept.
PMID- 29943261
TI - [Breastfeeding rate and promotion in selected European countries].
AB - BACKGROUND: Breastfeeding benefits the short- and long-term health of mothers and
their children. Breastfeeding promotion is an important task for society and the
healthcare system. AIMS: We report national breastfeeding data and monitoring
systems of selected European countries based on data provided by national
breastfeeding committees and international organisations. Strategies for
promoting, protecting and supporting breastfeeding, achievements and challenges
are reported. METHODS: Representatives of breastfeeding committees and
initiatives from Belgium, Croatia, Denmark, Germany, Italy, Ireland, Norway,
Sweden, Switzerland, Spain and The Netherlands completed a standardised
questionnaire. Reported results were compiled and complemented by additional
information compiled by the authors. RESULTS: Considerable differences in
breastfeeding rates, data collection and strategies for breastfeeding promotion
exist within Europe. At the age of 6 months 35-65% of infants are breastfed and
13-39% are fully or exclusively breastfed in the countries included. Varying
methods of breastfeeding monitoring are established in 7 of 11 countries (not in
Germany). National breastfeeding committees exist in 9 countries and a national
plan for breastfeeding promotion in 6 countries. All country representatives
supported stronger European collaboration on improved breastfeeding promotion.
CONCLUSIONS: Governments and health systems should collaborate in strengthening
evidence based breastfeeding monitoring and promotion and implement financial and
policy support. Sustained enhanced collaboration of European countries with
exchange of information and experience on breastfeeding support and a new
initiative for establishing a strategic European masterplan on breastfeeding
promotion appear necessary.
PMID- 29943262
TI - Family Care Curriculum: A Parenting Support Program for Families Experiencing
Homelessness.
AB - Purpose In the United States, families with children characterize the fastest
growing portion of the homeless population. Parenting for families experiencing
homelessness presents unique challenges since families facing homelessness are
disproportionately more likely to experience a myriad of interpersonal and
contextual stressors that heighten the risk of parents engaging in suboptimal
parenting approaches. This article describes the development and implementation
of the Family Care Curriculum (FCC) train-the-trainer parenting support program
specifically designed to support positive parenting in families experiencing
homelessness. Description The FCC is a 6-week theory-based parenting intervention
aimed to create positive shifts in parental attitudes to enhance sensitive and
nurturing parenting and positive parent-child relationships. FCC assists parents
in reflecting on how their own experiences contribute to some of their parenting
beliefs, patterns, and behaviors. Parents are coached to imagine and understand
the emotions, attachment, and developmental needs behind their children's
behaviors so they can maintain empathic and nurturing parenting responses in the
context of cumulative and chronic stress. Parents are supported through learning
to engage in self-care. A unique and important feature of the FCC is the
inclusion of a culturally sensitive approach that takes into consideration the
effects of racism, classism, and oppression on parent-child relationships.
Conclusion FCC was designed, implemented, and championed by expert providers in
the fields of family therapy, social work, and pediatrics to support parents
experiencing homelessness. FCC adds to the body of effective attachment-based,
trauma-informed, and culturally sensitive parenting interventions for improving
parent-child relations and family health amongst vulnerable populations.
PMID- 29943263
TI - Liquid-liquid interfacial self-assembled Au NP arrays for the rapid and sensitive
detection of butyl benzyl phthalate (BBP) by surface-enhanced Raman spectroscopy.
AB - Recent years have seen a large number of incidents involving the contamination of
liquor with phthalate plasticizers (PAEs). There is therefore an urgent need to
develop novel analytical strategies for the rapid and sensitive detection of
PAEs. The PAE butyl benzyl phthalate (BBP) is very harmful to the human body, so
we developed a surface-enhanced Raman spectroscopy (SERS) platform for the rapid
detection of BBP in liquor based on liquid-liquid extraction and the simultaneous
self-assembly of arrays of Au nanoparticles (Au NPs) at an organic/aqueous
interface. The self-assembly of Au NPs occurs under the influence of the surface
tension at the interface between the immiscible solvents. In the first step of
the strategy, cyclohexane (CYH) is mixed with BBP-containing liquor to extract
the BBP. Then the self-assembly of Au NPs at an organic/aqueous interface is
induced using the CYH supernatant as the organic phase, a colloid of Au NPs as
the aqueous phase, and ethanol as the inducer. During this process, the BBP
molecules extracted from the liquor participate directly in the Au NP self
assembly process, which causes the analytes to be loaded into SERS-active
nanogaps in the Au NP arrays, thus permitting the sensitive detection of BBP. BBP
levels as low as 1.3 mg/kg in the liquor were detected using this method. Fifteen
batches of the assembled SERS platform produced a relative standard deviation of
10.58% in the SERS intensity of the peak at 1178 cm-1 generated in the presence
of 0.08 ppm crystal violet, indicating that this strategy possesses good
reproducibility. Furthermore, interfacial assembly allowed the dual-analyte
detection of BBP in the organic phase and an edible pigment (sunset yellow) in
the aqueous phase to be achieved with high sensitivity and credible
reproducibility using the SERS platform. Interfacial self-assembled SERS-active
arrays therefore show great potential for the rapid and sensitive in situ
detection of BBP in liquor samples. Graphical abstract ?.
PMID- 29943264
TI - Molecularly imprinted polymers combined with membrane-protected solid-phase
extraction to detect triazines in tea samples.
AB - Spherical molecularly imprinted polymers (MIPs) were prepared by emulsion
polymerization. The isothermal adsorption and selective adsorption indicated that
the MIPs obtained exhibit excellent specific recognition for the template
(atrazine) and its analogues. The MIPs were encapsulated in a polypropylene
microporous membrane to fabricate MIP adsorption packages for the direct
extraction of triazines in uncentrifuged and unfiltered tea extracts. The
extraction conditions affecting the extraction efficiency, including the type and
volume of extraction solvent, the number of MIP adsorption packages, the surface
area of the MIP adsorption packages, the mass of MIPs in the MIP adsorption
packages, the extraction time, the eluting solvent, and the eluting volume, were
optimized. Under the optimal extraction and high-performance liquid
chromatography-tandem mass spectrometry conditions, the method exhibited
excellent linearity in the range from 0.5 to 250 ng g-1, with R2 >= 0.9992. The
detection limit of the method was 0.09-0.18 ng g-1. The intraday and interday
relative standard deviations ranged from 3.1% to 7.5% and from 3.1% to 7.9%,
respectively. The method was successfully used to detect triazines in five tea
samples. At a spiking concentration of 2 ng g-1, satisfactory recoveries ranging
from (81 +/- 3)% to (104 +/- 7)% were obtained. The membrane-protected solid
phase extraction method based on molecularly imprinted material is expected to be
widely used to enrich triazines in complex samples. Graphical Abstract Schematic
illustration of the MIPs combined with membrane-protected solid-phase extraction
of triazines in tea sample.
PMID- 29943265
TI - Cataluminescence sensing of carbon disulfide based on CeO2 hierarchical hollow
microspheres.
AB - Material morphology-dependent cataluminescence (CTL) sensing characteristic and
application are presented in this work. Hierarchical hollow microspheres CeO2
were synthesized via the hydrothermal reaction of glucose and N, N-dimethyl
formamide (Glu-DMF). SEM, XRD, TEM, HRTEM and BET were used to characterize the
prepared CeO2 materials. Compared with CeO2 cubics (CeO2 Cubs), CeO2 hierarchical
hollow microspheres (CeO2 HMs) show an enhanced CTL response to carbon disulfide.
The response and recovery times of CeO2 HMs-based CTL sensor towards carbon
disulfide are about 8 s and 20 s, respectively. CeO2 HMs exhibits a linear CTL
response to carbon disulfide in the concentration range of 0.50~10 MUg*mL-1 with
an excellent sensitivity and selectivity. These results suggest that CeO2 HMs
will be a highly promising CTL sensing material for the detection and monitoring
carbon disulfide. Graphical abstract CeO2 hierarchical hollow microspheres (CeO2
HMs) were synthesized via the hydrothermal reaction of glucose and N, N-dimethyl
formamide (Glu-DMF). Meanwhile, the prepared CeO2 HMs shows commendable CTL
response towards carbon disulfide. Due to the excellent analytical performance of
designed CeO2 HMs-based sensor for carbon disulfide, it has potential application
value in various locations.
PMID- 29943266
TI - Characterization of a nanoflow sheath liquid interface and comparison to a sheath
liquid and a sheathless porous-tip interface for CE-ESI-MS in positive and
negative ionization.
AB - Coupling of capillary electrophoresis to electrospray mass spectrometry still
remains challenging and a topic of research to find the best interface regarding
sensitivity, robustness, and ease of use. Here, a nanoflow sheath liquid
interface for CE-ESI-MS is presented and compared to both a standard triple-tube
sheath liquid and a porous-tip sheathless interface for three groups of analytes.
The nanoflow sheath liquid interface with a separation capillary inserted into a
glass emitter was initially characterized to facilitate optimization and method
development. Implementation of a shut-off valve, syringe pump, and inline filter
enabled easy handling and fast analyses, repeatable both in positive and negative
modes (intra-day RSD of 6.6 to 12.0%). The same setup was used for sheathless
interfacing by exchanging the emitter and using a porous etched tip separation
capillary. Both nanoflow interfaces showed similar performance. Average peak
areas using the nanoflow sheath liquid interface were a factor of 38 for 6
organic acids in negative mode, 114 and 36 for the light and heavy chain of a
monoclonal antibody, and 13 higher for peptides in positive mode compared to the
triple-tube interface. This first direct comparison of the three most common
interfaces exhibits a strong improvement in sensitivity to the same extent for
both nanoflow interfaces, where sheath liquid interfaces offer full flexibility
in method development.
PMID- 29943267
TI - The value of radical radiotherapy in the primary tumor of newly diagnosed oligo
metastatic nasopharyngeal carcinoma patients.
AB - BACKGROUND: To explore the efficacy and patterns of treatment failure of radical
radiotherapy in newly diagnosed oligo-metastatic nasopharyngeal carcinoma
patients. METHODS: We included 39 newly diagnosed oligo-metastatic nasopharyngeal
carcinoma patients who received radical radiotherapy and chemotherapy in Zhejiang
Cancer Hospital. Treatment and prognosis information were collected. The Kaplan
Meier methods and Cox proportional hazards models were used to calculate survival
rates and analyze prognostic factors. RESULTS: After a median follow-up time of
38 months, the 1-, 3-, and 5-year overall survival rates were 97, 70, and 57.9%,
while the 1-, 3-, and 5-year progression-free survival rates were 87, 59, and
50.9%, respectively. Age, numbers of metastases lesions, cycles, and schemes of
chemotherapy were independent prognostic factors of the overall survival.
Patients with no more than three metastasis lesions had a higher survival rate
than those with >= 3 metastatic lesions (P = 0.023). More than four cycles
chemotherapy provide a higher survival rate than less than four cycles.
Chemotherapy including docetaxel had a significantly survival advantages (P =
0.041). CONCLUSION: Radical radiotherapy is important for newly diagnosed oligo
metastatic nasopharyngeal carcinoma patients, which can still achieve long-term
survival after chemo-radiotherapy.
PMID- 29943268
TI - The interactions between tree-herb layer diversity and soil properties in the
oriental beech (Fagus orientalis Lipsky) stands in Hyrcanian forest.
AB - This study investigated the interactions between tree-herb layer diversity and
some physico-chemical and eco-physiological characteristics of soil in natural
oriental beech stand in western Guilan, Iran. The data were collected from nine
research sites (50 m * 50 m) which were described as a gradient from pure
oriental beech (Fagus orientalis Lipsky) stands to mixed stands with up to nine
deciduous tree species (n = 27) in Hyrcanian forest. Herbaceous plants were
sampled within ten 1 m * 1 m sub-plots in two plots of 400 m2 which were
installed randomly in each research site. Composite soil samples were taken at
five positions in each research site. We found that the increase in tree
diversity in mature oriental beech stands brought about an increase in microbial
biomass carbon, soil carbon content, and the ratio of microbial biomass carbon to
the organic carbon (Cmic/Corg). Increased soil organic carbon raised microbial
biomass carbon through creating suitable environment for microorganisms. The
findings also indicated that the ratio of microbial biomass carbon to the organic
carbon (Cmic/Corg) increased as a quantitative indicator of soil carbon dynamics
that finally benefits soil fertility of mixed oriental beech stands compared to
pure oriental beech stands. The results showed that humus layer and litter
thickness were negatively correlated with tree layer richness. Generally, it can
be stated that maintaining a mixture of tree layer species in natural oriental
beech stands results in an increase in richness and diversity values of herb
plants as well as carbon content and microbial biomass carbon of soil.
PMID- 29943270
TI - Renal sympathetic denervation induces changes in heart rate variability and is
associated with a lower sympathetic tone.
AB - BACKGROUND: Renal nerve stimulation (RNS) is used to localize sympathetic nerve
tissue for selective renal nerve sympathetic denervation (RDN). Examination of
heart rate variability (HRV) provides a way to assess the state of the autonomic
nervous system. The current study aimed to examine the acute changes in HRV
caused by RNS before and after RDN. METHODS AND RESULTS: 30 patients with
hypertension referred for RDN were included. RNS was performed under general
anesthesia before and after RDN. Heart rate (HR) and blood pressure (BP) were
continuously monitored. HRV characteristics were assessed 1 min before and after
RNS and RDN. RNS before RDN elicited a maximum increase in systolic BP of 45 (+/-
22) mmHg which was attenuated to 13 (+/- 12) mmHg (p < 0.001) after RDN. RNS
before RDN decreased the sinus cycle length from 1210 (+/- 201) ms to 1170 (+/-
203) ms (p = 0.03), after RDN this effect was blunted (p = 0.59). The LF/HF ratio
in response to RNS changed from ? + 0.448 (+/- 0.550) before RDN to ? - 0.656 (+/
0.252) after RDN (p = 0.02). Selecting patients off beta-blockade (n = 11), the
RNS-induced changes in HRV components before versus after RDN were more
pronounced (LF/HF ratio ? + 0.900 +/- 1.171 versus ? - 0.828 +/- 0.519, p =
0.01), whereas changes in HRV parameters in patients on beta-blockade (n = 19)
were no longer significant. In patients with diabetes mellitus (n = 7), RNS
induced no changes in HRV parameters (LF/HF ratio ? - 0.039 +/- 0.103 versus ? -
0.460 +/- 0.491, p = 0.92). CONCLUSION: RNS induces changes in HRV suggesting
increased sympathetic activity. Conversely, after RDN, the RNS-induced changes in
HRV suggesting a lower sympathetic autonomic balance. These changes were most
pronounced in beta-blocker naive patients and not present in patients with
diabetes mellitus. These findings could support RNS-guided RDN to optimize
results.
PMID- 29943269
TI - Postoperative complications after elective coronary artery bypass grafting
surgery in patients with sleep-disordered breathing.
AB - BACKGROUND: Sleep-disordered breathing (SDB) may increase the risk of
postoperative complications in patients after cardiac surgery. This study
evaluated the length of hospital stay as well as postoperative cardiac,
respiratory, and renal complications after elective coronary artery bypass
grafting (CABG) in patients without SDB, with central sleep apnea (CSA), or with
obstructive sleep apnea (OSA). METHODS: The presence and type of SDB had been
assessed with polygraphic recordings in 100 patients the night before elective
CABG surgery. SDB was defined as an apnea-hypopnea index (AHI) of >= 15/h.
Prolonged length of hospital stay (LOS) and postoperative hemodynamic instability
due to any cause were retrospectively evaluated as primary endpoints and cardiac,
respiratory, and renal complications as secondary endpoints. RESULTS: 37% of
patients had SDB, 14% CSA, and 23% OSA. LOS differed significantly between
patients without SDB and those with CSA and OSA [median (25;75. percentile): 8.0
days (7.5;11.0) vs. 9.5 days (7.0;12.5) vs. 12.0 days (9.0;17.0), Kruskal-Wallis
test between three groups: p = 0.023; OSA vs. no SDB: p = 0.005]. AHI was
significantly associated with prolonged LOS [> 9 days; odds ratio (OR) (95%
confidence interval): 1.047 (1.001;1.095), p = 0.044]. Prolonged need of
vasopressors (>= 48 h) was observed in 36% of patients without SDB, in 64% with
CSA, and in 62% with OSA (p = 0.037). AHI was significantly associated with
prolonged (>= 48 h) need of vasopressors [OR (95% CI): 1.052 (1.002;1.104), p =
0.040], independent of any confounders. CONCLUSIONS: SDB, particularly OSA, is
associated with prolonged LOS after CABG, independent of known confounders.
Prolonged LOS in patients with SDB may be due to increased postoperative
hemodynamic instability due to any cause.
PMID- 29943271
TI - Long-term effects of device-guided slow breathing in stable heart failure
patients with reduced ejection fraction.
AB - BACKGROUND: Slow breathing (SLOWB) alleviates symptoms of chronic heart failure
(HF) but its long-term effects are unknown. We examined the acute and long-term
impact of device-guided breathing on hemodynamics and prognostic parameters in HF
patients with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Twenty-one
patients with HFrEF (23.9 +/- 5.8%, SD +/- mean) on optimal medical therapy
underwent blood pressure (BP), heart rate (HR), HR variability, 6-min walk test
(6MWT), cardiopulmonary exercise testing (CPET), and echocardiography
measurements before and 3 months after SLOWB home training (30 min daily). After
3 months, all patients were assigned to continue SLOWB (Group 1) or no-SLOWB
(Group 2). All tests were repeated after 6 months. Acute SLOWB (18 +/- 5 vs 8 +/-
2 breaths/min, P < 0.001) had no influence on BP and HR but improved saturation
(97 +/- 2 vs 98 +/- 2%, P = 0.01). Long-term SLOWB reduced office systolic BP (P
< 0.001) but not central or ambulatory systolic BP. SLOWB reduced SDNN/RMSSD
ratio (P < 0.05) after 3 months. One-way repeated measures of ANOVA revealed a
significant increase in 6MWT and peak RER (respiratory exchange ratio) from
baseline to 6-month follow-up in group 1 (P < 0.05) but not group 2 (P = 0.85 for
6MWT, P = 0.69 for RER). No significant changes in echocardiography were noted at
follow-up. No HF worsening, rehospitalisation or death occurred in group 1 out to
6-month follow-up. Two hospitalizations for HF decompensation and two deaths
ensued in group 2 between 3- and 6-month follow-up. CONCLUSIONS: SLOWB training
improves cardiorespiratory capacity and appears to slow the progression of HFrEF.
Further long-term outcome studies are required to confirm the benefits of paced
breathing in HFrEF.
PMID- 29943272
TI - Heart Valve Disease Awareness Survey 2017: what did we achieve since 2015?
AB - AIMS: The 2015 Heart Valve Disease Awareness Survey showed a low knowledge and
awareness about heart valve disease in the general population despite its high
prevalence and morbidity. The 2017 survey was conducted to re-evaluate concern
and knowledge about heart valve disease after 2 years of rapidly increasing
patient numbers presenting with heart valve disease. METHODS AND RESULTS: A total
of 12,820 people aged 60 years or older in 11 European countries took part in the
survey. While the number of people concerned most about heart valve disease
increased significantly (2015:1.7% vs. 2017:2.1%; p < 0.001), it is still very
low compared to cancer (28.8%) or Alzheimer's disease (20.9%). More people claim
to be familiar with heart valve disease in general (2015: 17.1% vs. 2017: 20.0%;
p < 0.001) and the majority claims to know of at least one therapy for heart
valve disease (61.9%). Nevertheless, only 3.8% could correctly identify aortic
stenosis (AS), which is significantly less than in 2015 (7.2%; p < 0.001). As
before, the majority of the respondents claimed to rarely or never undergo a
stethoscope check from their general practitioner (2015: 54.2% vs. 2017: 50.6%, p
< 0.001); nevertheless, a positive trend can be seen. People wish heart valve
disease to be part of regular checks by the general practitioners. CONCLUSION:
The general population's knowledge of heart valve disease in general slightly
increased over the last 2 years. However, detailed understanding of aortic
stenosis and its treatment options is still low, as is the level of concern shown
for heart valve disease. Nevertheless, the general population cites heart valve
disease as a condition they wish to be checked for regularly.
PMID- 29943273
TI - Gender-dependent association of diabetes mellitus with mortality in patients
undergoing transcatheter aortic valve replacement.
AB - BACKGROUND: Diabetes mellitus (DM) is a risk factor for cardiovascular disease.
However, its effect on procedural and follow-up performance after transcatheter
aortic valve replacement (TAVR) remains controversial. METHODS AND RESULTS: We
performed an observational study of all consecutive patients treated with a
transfemoral TAVR in a single-center cohort (n = 1818). All patients were
stratified by diabetes status and gender. All-cause 3-year mortality was the
primary endpoint. Male patients with DM were identified to have substantially
increased 3-year mortality [125/314 (39.8%)] compared to males without DM
[142/478 (29.7%), p < 0.01]. Male patients with DM had significantly higher 3
year mortality in comparison to female patients with (p < 0.01) or without DM (p
< 0.01). There was no difference in 3-year mortality for female patients with
[135/465 (29.0%)] and without DM [151/554 (27.3%); p = 0.70]. This increase in
mortality in male DM patients was triggered by both cardiovascular and non
cardiovascular mortality. Furthermore, DM served as an independent predictor of 3
year mortality after TAVR selectively only in men. The interaction between male
gender and diabetes mellitus was identified as an independent predictor of 3-year
mortality [HR 1.88 (1.25; 2.82); p < 0.01]. DM did not affect 30-day mortality
for the overall cohort and for males. CONCLUSION: Males with DM are a high-risk
subgroup of patients after TAVR and require close medical attention including
aggressive therapy of modifiable risk factors. Intensified diabetes management
may improve long-term survival after TAVR.
PMID- 29943274
TI - Optimal Conditions for the Asymmetric Polymerase Chain Reaction for Detecting
Food Pathogenic Bacteria Using a Personal SPR Sensor.
AB - We have been developing quick and simple system for detecting food-poisoning
bacteria using a combination of an asymmetric PCR and a portable surface plasmon
resonance (SPR) sensor. The system would be suitable for point-of-care detection
of food-poisoning bacteria in the field of food industry. In this study, we
established a novel method for quantifying the amplified forward (F) and reverse
(R) chains of Staphylococcus aureus separately by high-performance liquid
chromatography (HPLC). The concentration of single-stranded DNA amplicon
excessively amplified, which is crucial for the system, could be calculated as
the difference between those of the F- and R-chains. For the R-chain, a
correction based on the F-chain concentration in the sample was used to obtain a
more accurate value, because the determination of the R-chain concentration was
affected by that of the coexisting F-chain. The concentration values were also
determined by fluorescence imaging for electrophoresis gels of amplicons with
FITC- or Cy5-conjugated primers, and they were in good agreement with the values
by the HPLC. The measured concentration of the single-strand F-chain correlated
well with the value of the SPR response against the probe that was a
complementary sequence of the F-chain, immobilized on the sensor chip of the SPR
sensor.
PMID- 29943275
TI - Anti-Diabetic and Anti-Nephritic Activities of Grifola frondosa Mycelium
Polysaccharides in Diet-Streptozotocin-Induced Diabetic Rats Via Modulation on
Oxidative Stress.
AB - Grifola frondosa is an edible fungus with a variety of potential pharmacological
activities. This study investigates the hypoglycemic, anti-diabetic nephritic,
and antioxidant properties of G. frondosa polysaccharides in diet-streptozotocin
induced diabetic rats. After a 4-week treatment with 100 mg/kg of metformin and
200 mg/kg of one of four different G. frondosa polysaccharide mixtures
(especially GFPS3 and GFPS4), diabetic rats had enhanced body weight and
suppressed plasma glucose, indicating the hypoglycemic activities of the G.
frondosa polysaccharides. G. frondosa polysaccharides regulated the level of
serum creatinine, blood urea nitrogen, N-acetyl-beta-D-glucosaminidase, and
albuminuria; inhibited the serum levels of interleukin (IL)-2, IL-6, and TNF
alpha; and enhanced the serum levels of matrix metalloproteinase 9 and interferon
alpha, confirming their anti-diabetic nephritic activities. G. frondosa
polysaccharides ameliorated the pathological alterations in the kidneys of
diabetic rats. Moreover, G. frondosa polysaccharides modulated the serum levels
of oxidant factors such as superoxide dismutase, glutathione peroxidase,
catalase, malondialdehyde, and reactive oxygen species, revealing their
antioxidant properties. Furthermore, the administration of G. frondosa
polysaccharides inhibited nuclear factor kappa B activities in the serum and
kidneys. All of the data revealed that the activation of nuclear factor kappa B
plays a central role in G. frondosa polysaccharide-mediated anti-diabetic and
anti-nephritic activities.
PMID- 29943276
TI - Differences in the interpretation of a modernized Mediterranean diet prescribed
in intervention studies for the management of type 2 diabetes: how closely does
this align with a traditional Mediterranean diet?
AB - PURPOSE AND METHODS: Adherence to Mediterranean diet (MedDiet) is associated with
the prevention and management of type 2 diabetes mellitus (T2DM). However, in
intervention studies, there is discordance in the interpretation of a MedDiet.
The purpose of this paper was to examine, synthesize, and develop a narrative
review, exploring the qualitative differences in the interpretation of a
modernized MedDiet prescribed as an intervention in clinical trials for the
management of T2DM, and how closely this aligns with a traditional MedDiet. The
'traditional' MedDiet is often described as a dietary pattern high in unprocessed
plant foods (fruits, vegetables, legumes, nuts, wholegrain cereals, and olive
oil); moderate consumption of wine; low moderate in fish/shellfish; and an
infrequent consumption of red meat, animal fats, vegetable oils, and processed
foods. RESULTS AND CONCLUSIONS: Synthesis of the reviewed literature demonstrates
considerable variation in the qualitative interpretation of a MedDiet. We also
identified inadequate reporting of MedDiet interventions, despite a number of
studies referring to their intervention as a 'traditional' MedDiet. The majority
of studies emphasized the same key dietary components and principles: an
increased intake of vegetables, wholegrains, and the preferential consumption of
white meat in substitute of red and processed meat and abundant use of olive oil.
However, the reporting of specific dietary recommendations for fruit, legumes,
nuts, bread, red wine, and fermentable dairy products were less consistent or not
reported. Irrespective of the discordance in the interpretation of a MedDiet, a
number of studies included in the present review reported improved glycaemic
control and favorable cardiovascular outcomes with adherence to a Mediterranean
style diet. Nevertheless, greater clarity and depth of reporting amongst
intervention studies is warranted for the refinement of a modernized MedDiet
definition that is distinct from a prudent dietary pattern.
PMID- 29943277
TI - Primary Care and Neurology in Psychiatry Residency Training: a Survey of Early
Career Psychiatrists.
AB - OBJECTIVE: A survey of recently certified psychiatrists was conducted to obtain
their feedback about the contribution of the primary care and neurology
components of residency training to their professional development and to their
current needs as practitioners. METHODS: A 22-item survey was developed based on
issues discussed at a forum on residency competence requirements and administered
electronically to four cohorts of recently certified psychiatrists. RESULTS: The
response rate was 17% (1049/6083). Overall, the respondents described both their
primary care and neurology experiences as helping them accomplish several goals
for their professional development. The majority were satisfied with their
primary care training and felt well-prepared to enter practice. The most common
suggestions for improving the primary care component were better integration with
psychiatry and providing longitudinal experiences and more outpatient experience.
They were somewhat less satisfied with their neurology training, and only about
half felt well-prepared for the neurologic aspects of psychiatry practice. The
most common suggestions for improving neurology training were to provide more
time in neurology with experiences that were more relevant to psychiatry such as
outpatient and consultation experiences. Some also thought longitudinal
experiences would be useful. CONCLUSIONS: These psychiatrists were generally
satisfied with the primary care and neurology components of residency training
and felt that they had contributed to their professional development. Their
suggestions for improvement contribute to the rich discussion among training
directors and other psychiatry educators about these components of residency
training.
PMID- 29943278
TI - Authorized Generic Drugs: an Overview.
AB - In the United States (U.S.), an authorized generic (AG) drug is essentially the
approved brand-name drug (i.e., innovator drug), but marketed with a different
name. Like independent generics, authorized generics (AGs) generally tend to cost
less than their brand name counterpart, even though AGs are essentially identical
to the brand. Most patients and health professionals are unaware of the
availability of AGs even though they are commonplace. The launch of an AG has a
financial impact on patients and on the competitive landscape of the
pharmaceutical industry. Information regarding AGs is limited. The purpose of
this study is to familiarize the reader with AGs. A review of the government
documents and literature was conducted. The marketing of AGs has resulted, but
not always, in benefits to the patient. AGs have been used as a tool in
agreements between brand and generic companies. Countries have differing
allowance and approval policies for AGs. AGs have played an important role in the
healthcare system.
PMID- 29943279
TI - Thermal Behavior of 19F Nuclear Magnetic Resonance Signal of 19F-Containing
Compound in Lipid Nano-Emulsion for Potential Tumor Diagnosis.
AB - We developed carriers of a 19F magnetic resonance imaging (19F MRI) agent,
capable of responding to the temperature difference for cancer diagnosis. The
carriers were based on high melting point (mp) neutral lipids, namely,
tripalmitin (TPT) and tristearin (TSR) and triarachidin (TAC). Lipid nano
emulsions (LNEs) containing a fluorine compound, i.e., a modified alpha
tocopherol (19F-TP), were respectively prepared as TPT-LNE, TSR-LNE, TAC-LNE1,
and TAC-LNE2 and studied by 19F NMR spectroscopy. In LNE prepared with soybean
oil as a control, the full width at half maximum (FWHM) values of the 19F NMR
signal of 19F-TP remained constant at 25, 37, and 42 degrees C, while those of
the LNEs prepared from a neutral lipid with a high mp showed a sharp decrease
between 25 and 37 degrees C. The magnitude of the decrease followed the order:
TPT-LNE < TSR-LNE < TAC-LNE1. However, TAC-LNE2, for which the amount of
encapsulated 19F-TP was one third less than that of TAC-LNE1, showed a sharp
decline in the FWHM between 37 and 42 degrees C. To examine these changes, the
19F spin-lattice (T1) and spin-spin (T2) relaxation times of 19F-TP were
measured. TAC-LNE2 in particular showed a substantial change in its T2 value
between 37 and 42 degrees C compared with the change of its T1 value. This result
was attributed to activation of the molecular motion of 19F-TP in TAC-LNE2 from
37 to 42 degrees C. Thus, TAC-LNE showed potential for use as a carrier for
cancer diagnosis using 19F MRI.
PMID- 29943280
TI - Co-Processed Excipients for Dispersible Tablets-Part 2: Patient Acceptability.
AB - Palatability and patient acceptability are critical attributes of dispersible
tablet formulation. Co-processed excipients could provide improved organoleptic
profile due to rational choice of excipients and manufacturing techniques. The
aim of this study was to identify the most suitable co-processed excipient to use
within directly compressible dispersible tablet formulations. Nine excipients,
selected based on successful manufacturability, were investigated in a
randomised, preference and acceptability testing in 24 healthy adult volunteers.
Excipients were classified in order of preference as follows (from most
preferred): SmartEx QD100 > F-Melt Type C > F-Melt Type M > MicroceLac >
Ludiflash > CombiLac > Pharmaburst 500 > Avicel HFE-102 > Avicel PH-102. Broad
differences were identified in terms of acceptability, with SmartEx QD100 being
'very acceptable', F-Melt Type C, F-Melt Type M and MicroceLac being
'acceptable', Ludiflash, CombiLac and Pharmaburst 500 being 'neutral' and Avicel
products being 'very unacceptable' based on ratings using five-point hedonic
scales. Organoleptic differences were ascribed to different composition and
physical properties of excipients, resulting in dissimilar taste and mouth-feel.
Excipients with particle size in water larger than 200-250 MUm were considered
poorly acceptable, which supports the use of this value as a threshold for
maximum particle size of dispersible formulation. The most promising co-processed
excipients for directly compressible dispersible tablets were successfully
identified.
PMID- 29943281
TI - Pharmaceutical Additive Manufacturing: a Novel Tool for Complex and Personalized
Drug Delivery Systems.
AB - Inter-individual variability is always an issue when treating patients of
different races, genders, ages, pharmacogenetics, and pharmacokinetic
characteristics. However, the development of novel dosage forms is limited by the
huge investments required for production line modifications and dosages
diversity. Additive manufacturing (AM) or 3D printing can be a novel alternative
solution for the development of controlled release dosages because it can produce
personalized or unique dosage forms and more complex drug-release profiles. The
primary objective of this manuscript is to review the 3D printing processes that
have been used in the pharmaceutical area, including their general aspects,
materials, and the operation of each AM technique. Advantages and shortcomings of
the technologies are discussed with respect to practice and practical
applications. Thus, this review will provide an overview and discussion on
advanced pharmaceutical AM technologies, which can be used to produce unique
controlled drug delivery systems and personalized dosages for the future of
personalized medicine.
PMID- 29943282
TI - Amisulpride-CD-Loaded Liposomes: Optimization and In Vivo Evaluation.
AB - Amisulpride (AMS) is an atypical antipsychotic agent used for the treatment of
schizophrenia. The effect of different variables, i.e., the type of cyclodextrins
(CDs), ratio of drug/CDs, and type of loading on the prepared AMS-CD liposomes
(single and double loaded) was studied by applying 23 full factorial design.
Double-loaded liposomes are loaded with AMS-hydroxyl propyl-beta-cyclodextrin (HP
beta-CD) in the aqueous phase and free drug in the lipophilic bilayer, while
single-loaded liposomes are loaded only with AMS-HP-beta-CD in the aqueous phase.
Entrapment efficiency, particle size, polydespersibility, and zeta potential were
selected as dependent variables. Design Expert(r) software was used to obtain an
optimized formulation with high entrapment efficiency (64.55 +/- 1.27%), average
particle size of 40.1 +/- 2.77 nm, polydespersibility of 0.44 +/- 0.37, and zeta
potential of - 48.8 +/- 0.28. Optimized formula was evaluated for in vitro
release, surface morphology and stability study was also conducted. AMS-HP-beta
CD in double-loaded liposomes exhibited higher drug release than those in the
conventional liposomes and in the single-loaded liposomes. The maximum plasma
concentration (Cmax) of AMS in optimized AMS-HP-beta-CD double-loaded liposomal
formulation increased by 1.55- and 1.29-fold, as compared to the commercial
tablets and conventional liposomes, respectively. However, the relative
bioavailability of AMS double-loaded liposomes was 1.94- and 1.28-folds of
commercial tablet and conventional liposomes, respectively.
PMID- 29943283
TI - Nanoemulsion-Loaded Hydrogels for Topical Administration of Pentyl Gallate.
AB - The aim of this study is to describe the development of nanoemulsion-loaded
hydrogels to deliver pentyl gallate (PG), a gallic acid n-alkyl ester, through
the skin. PG is an antioxidant agent; however, it seems to be a promising agent
for herpis labialis treatment. Aristoflex AVC(r) and chitosan were used as
gelling agents for nanoemulsion thickening. The developed formulations presented
suitable PG content (94.4-100.3% w/w), nanometric droplet sizes (162-297 nm),
high zeta potentials, and a non-Newtonian pseudoplastic behavior. Both vehicles
neither enhanced PG penetration nor delayed its release from the nanoemulsion.
Formulations remained physically stable at 8 degrees C during 3 months of
storage.
PMID- 29943284
TI - The lingual nerve: overview and new insights into anatomical variability based on
fine dissection using human cadavers.
AB - This article, for both researchers and clinicians, presents an overview of the
lingual nerve and highlights how new insights into human anatomical variability
can be gained by integrating fine dissection of cadavers with neuroanatomical
approaches, microscopic studies, and morphometric techniques. Textbooks mainly
provide descriptions of the typical or common gross anatomical appearance of
structures in the human body with little reference to the nature and extent of
variation that may be encountered within and between populations. Furthermore,
few texts attempt to integrate descriptions of the regional distribution and
branching of neural structures with their central connections or their
microscopic anatomy. Using the lingual nerve as an example from the head and neck
region, we show that there is still an important place for detailed fine
dissections of human cadavers when they are also integrated with morphometric
techniques applied to data representing observed variation at both macro- and
micro-levels. It is essential that health professionals have a sound
understanding of the nature and extent of anatomical variation displayed normally
by their patients so that they can perform procedures, such as local anaesthesia
and surgery, safely and also be able to correctly diagnose pathology when it is
present.
PMID- 29943285
TI - An analysis of the interactions between folic acid and aromatic guest molecules.
AB - The formation of complexes between folate and therapeutic drug molecules is well
known. In this work, we attempted to elucidate the role of the aromatic rings of
folate and drug molecules in interactions between both of these molecules. A
detailed molecular simulation study was carried out to explore the associative
behavior of folic acid with phenylalanine and tyrosine, which show fluorescence
emission following the excitation of these molecules at 257 nm and 274 nm,
respectively. Therefore, studies of fluorescence emission from phenylalanine and
tyrosine were performed in this work. The results of these studies indicated that
folic acid associates with phenylalanine and tyrosine with binding constants
ranging from 1.46 * 104 to 2.66 * 104 M-1. X-ray diffraction studies suggested
that folic acid self-assembly is maintained in the presence of associative
interactions of the folic acid with guest molecules. These results demonstrate
that the aromatic rings in the structures of the folic acid and the therapeutic
drug play an important role in the encapsulation of guest molecules through
folate self-assembly.
PMID- 29943286
TI - Esophageal cancer associated with a sarcoid-like reaction and systemic
sarcoidosis in lymph nodes: supportive findings of [18F]-fluorodeoxyglucose
positron emission tomography-computed tomography during neoadjuvant therapy.
AB - BACKGROUND: In patients with esophageal cancer, differentiation between lymph
node metastasis and lymphadenopathies from sarcoidosis or sarcoid-like reactions
of lymph nodes is clinically important. Herein, we report two esophageal cancer
cases with lymph node involvement of sarcoid-like reaction or sarcoidosis. CASE
PRESENTATION: One patient received chemotherapy and the other chemoradiotherapy
as initial treatments. In both cases, [18F]-fluorodeoxyglucose positron emission
tomography-computed tomography (FDG-PET/CT) was performed before and after
chemo(radio)therapy. After the treatment, FDG uptake was not detected in the
primary tumor, but it was slightly reduced in the hilar and mediastinal lymph
nodes in both cases. These non-identical responses to chemo(radio)therapy suggest
the presence of sarcoid-like reaction of lymph nodes associated with squamous
cell carcinoma of the esophagus. Curative surgical resection was performed as
treatment. CONCLUSIONS: These FDG-PET/CT findings may be helpful to distinguish
between metastasis and sarcoidosis-associated lymphadenopathy in esophageal
cancer.
PMID- 29943287
TI - Investigation of the effect of homocysteinylation of substance P on its binding
to the NK1 receptor using molecular dynamics simulation.
AB - Substance P is a neurotransmitter or modulator in both the central and peripheral
nervous systems. In this work, modifications of the lysine in SP by homocysteine
and an acetyl group as well as the conformational dynamics of the native and
modified SP peptides and their complexes with the NK1 receptor were studied via
MD simulation. It was found that modifying SP stabilizes the peptide structure,
but the modified SP peptides are less likely to bind to the NK1 receptor, so the
resulting complexes are less stable. The RMSD of native SP (~0.33 nm) is about
twice as large as that of the modified SP peptides (~0.18 nm), while the RMSD for
the receptor complexed with native SP is ~0.3 nm, and that for the receptor
complexed with either of the modified peptides is ~0.35 nm, which demonstrates
the high stability of the modified SP peptides as well as the receptor complexed
with native SP. Such behavior was also observed in other structural analyses. The
binding free energies of the native and modified SP peptides with the NK1
receptor were also compared. The DeltaGbind values for the binding of
homocysteinylated SP to the NK1 receptor and the binding of the acetylated SP and
native SP to the NK1 receptor were -38.89, -64.46, and - 264.52 kJ mol-1,
respectively. Modification of the lysine of SP decreases the binding affinity of
the peptide to the NK1 receptor. In other words, homocysteinylation or
acetylation of SP leads to weaker interactions of the peptide with the NK1
receptor compared to those between native SP and NK1. We propose that this
phenomenon leads to increased levels of homocysteinylated SP in plasma in many
diseases such as breast cancer. Graphical abstract Substance P (SP) is a
neuropeptide which binds to the NK1 receptor. SP is of great pharmacological
interest, as agonists and antagonists of SP can potentially be used to treat many
chronic diseases. Therefore, in this work, the lysine (LYS) in SP was
theoretically modified with a homocysteine or acetyl group to explore the effects
of such a modification on the binding affinity of this peptide with the NK1
receptor and the structural dynamics of the resulting complex.
PMID- 29943288
TI - Genome-wide identification of the pectate lyase-like (PLL) gene family and
functional analysis of two PLL genes in rice.
AB - Pectate lyase catalyses the eliminative cleavage of de-esterified pectin, which
is a major component of primary cell walls in many higher plants. Pectate lyase
like (PLL) genes have been identified in various plant species and are involved
in a broad range of physiological processes associated with pectin degradation.
Previous studies have functionally identified two PLL genes in rice (Oryza
sativa. L). However, the knowledge concerning genome-wide analysis of this family
remains limited, and functions of the other PLL genes have not been thoroughly
elucidated to date. In this study, we identified 12 PLL genes based on a genome
wide investigation in rice. A complete overview of this gene family is presented,
including chromosomal locations, exon-intron structure, cis-acting elements and
conserved motifs. PLL protein sequences from multiple plant species were compared
and divided into five groups based on phylogenetic analysis. Quantitative RT-PCR
analysis revealed that only a portion of OsPLL genes (4 of 12) exhibits
detectable expression levels. Notably, OsPLL1, OsPLL3, OsPLL4 and OsPLL12 exhibit
strong and preferential expression in panicles suggesting that the potential
roles of these genes are crucial during rice panicle development. Moreover,
knockdown of OsPLL3 and OsPLL4 by artificial microRNA (amiRNA) disrupted normal
pollen development and resulted in partial male sterility. These results could
provide valuable information for characterising the functions and dissecting the
molecular mechanisms of the OsPLL genes.
PMID- 29943289
TI - Characterization of Vv-miR156: Vv-SPL pairs involved in the modulation of grape
berry development and ripening.
AB - SPL is a plant-specific transcription factor family. Many researchers reported
that SPL members targeted by miR156s could play crucial roles in the modulation
of plant growth and development. Although there are similar reports on grapes,
till now little is known about grape berry development and ripening. To gain more
insight into how grape miR156s (Vv-miR156s) modulated the above given processes
of grape berries by mediating their target gene Vv-SPLs, here we identified the
precise sequences of Vv-miR156s in 'Giant Rose' grape berries, predicted their
potential targets, and revealed that the matching degree of various Vv-miR156: Vv
SPL pairs exhibited some discrepancy, implying the divergence of their
interaction. Subsequently, we also discovered similar motifs such as ABRE, CGTCA
and ERE, which are more specific to berry development and ripening, within the
promoters of both Vv-MIR156s and Vv-SPLs. With berry development and ripening,
meanwhile, Vv-miR156a, b/c/d, e and f/g/i exhibited an overall increasing
expression trend, while their targets showed opposite trends at the corresponding
stages. Additionally, exogenous ABA and NAA application promoted or curbed the
expression of Vv-miR156s to some extent, before grape berry ripening stage. The
cleavage products, sites and frequencies of Vv-miR156a, b/c/d, e, f/g/i and their
respective targets (Vv-SPL2, 9, 10, 16) during grape berry development and
ripening process were validated by our developed PPM-RACE and modified RLM-RACE
together with qRT-PCR, which demonstrated that Vv-miR156s can be involved in the
modulation of grape berry development and ripening process by mediating the
expression of Vv-SPL2, 9, 10, 16. Our findings lay an important foundation for
further recognizing their functions in grape berries, and enrich the knowledge of
the regulatory mechanism of miRNA-mediated grape berry development and ripening.
PMID- 29943291
TI - Can the Single Cell Make Biomedicine Different?
AB - The single-cell as the basic unit of biological organs and tissues has recently
been considered an important window to furthermore understand molecular
mechanisms of organ function and biology. The current issue with a special focus
on single cell biomedicine is the first effort to collect the evidence of disease
associated single cell research, define the significance of single cell
biomedicine in the pathogenesis of diseases, value the correlation of single cell
gene sequencing with disease-specific biomarkers, and monitor the dynamics of RNA
processes and responses to microenvironmental changes and drug resistances.
PMID- 29943290
TI - Physiologically based pharmacokinetic-quantitative systems toxicology and safety
(PBPK-QSTS) modeling approach applied to predict the variability of amitriptyline
pharmacokinetics and cardiac safety in populations and in individuals.
AB - The physiologically based pharmacokinetic (PBPK) models allow for predictive
assessment of variability in population of interest. One of the future
application of PBPK modeling is in the field of precision dosing and personalized
medicine. The aim of the study was to develop PBPK model for amitriptyline given
orally, predict the variability of cardiac concentrations of amitriptyline and
its main metabolite-nortriptyline in populations as well as individuals, and
simulate the influence of those xenobiotics in therapeutic and supratherapeutic
concentrations on human electrophysiology. The cardiac effect with regard to QT
and RR interval lengths was assessed. The Emax model to describe the relationship
between amitriptyline concentration and heart rate (RR) length was proposed. The
developed PBPK model was used to mimic 29 clinical trials and 19 cases of
amitriptyline intoxication. Three clinical trials and 18 cases were simulated
with the use of PBPK-QSTS approach, confirming lack of cardiotoxic effect of
amitriptyline in therapeutic doses and the increase in heart rate along with
potential for arrhythmia development in case of amitriptyline overdose. The
results of our study support the validity and feasibility of the PBPK-QSTS
modeling development for personalized medicine.
PMID- 29943292
TI - Automated Single-Cell Analysis and Isolation System: A Paradigm Shift in Cell
Screening Methods for Bio-medicines.
AB - We have developed an automated robot that facilitates non-invasive isolation of a
single cell with the most favorable properties from arrays containing >105 cells,
thus allowing the establishment of new cell screening methods for bio-medicines.
In this chapter, an outline of the proposed automated single-cell analysis and
isolation system (hereafter called 'single-cell robot') is reviewed by comparison
with a conventional fluorescence-activated cell sorter (FACS). The single-cell
robot could perform high-throughput screening for both mammalian cells secreting
the highest amount of bio-medicines (e.g. Chinese hamster ovary (CHO) cells or
hybridomas), and stem cells with the highest pluripotency (e.g., embryonic stem
(ES) cells), from huge number of cell libraries based on the recently proposed
concept of "single cell-based breeding". The rational screening method for the de
novo agonist design could also be performed using yeast cells expressing
functional mammalian cytokine receptors (e.g., epidermal growth factor receptor
(EGFR), somatostatin G protein-coupled receptor (SSTR5), and interleukin 5
receptor (IL5R)). Furthermore, the single-cell robot could comprehensively
analyze the reaction between olfactory sensory neurons and specific odorants,
which will shed light on how odorants are recognized by olfactory receptors.
Taken together, these unique features of the proposed single-cell robot will
contribute to the high-throughput development of forthcoming bio-medicines.
PMID- 29943293
TI - Single-Cell Non-coding RNA in Embryonic Development.
AB - Non-coding RNAs (ncRNAs) have significant regulatory functions on the regulation
of gene expression of various life activities after transcription, even though
they do not encode proteins. During the development of embryos, ncRNAs, such as
long non-coding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs),
small nucleolar RNAs (snoRNAs), and Piwi-interacting RNAs (piRNAs), have been
widely proven as key regulators. The emerging single-cell RNA sequencing
technique is powerful for profiling "cell-to-cell" variability at the genomic
level. It has been applied to detect the expression of ncRNAs during embryo
development. In this chapter, we pay close attention to single-cell ncRNA
expression and summarize their roles in embryo development.
PMID- 29943295
TI - Circulating Tumor Cells: The Importance of Single Cell Analysis.
AB - Cancer cells that have shed from the primary tumor are able to invade into
surrounding tissues, to intravasate into the bloodstream to become circulating
tumor cells (CTCs), at least one part of that cells will be able to generate
distant metastases. The discovery of CTCs has improved the study of cancer
disease as it represents a non invasive biopsy that can be used as prognostic and
prediction biomarkers. Tumour heterogeneity is a concept related to differences
in tumor cells within the same tumor or between tumours in terms of genetic and
phenotypic profiles, such as morphology, metabolic activity, proliferation rate,
migration and metastatic abilities. Characterization of heterogeneity among CTCs
at the single cell level may be useful to better understand the causes and
progression of disease and for an accurate selection of molecular
prognostic/prediction markers. In this chapter we aimed to describe methods for
CTC enrichment and isolation as well as current methodologies for single cell
analysis at different levels, including RNA, DNA, protein and epigenetic events.
Finally we wanted to stress clinical and biological importance of single CTC
analysis by reviewing some studies carried out in different cancer subtypes.
PMID- 29943294
TI - High Throughput Single Cell RNA Sequencing, Bioinformatics Analysis and
Applications.
AB - Single cell sequencing (SCS) can be harnessed to acquire the genomes,
transcriptomes and epigenomes from individual cells. Next generation sequencing
(NGS) technology is the driving force for single cell sequencing. scRNA-seq
requires a lengthy pipeline comprising of single cell sorting, RNA extraction,
reverse transcription, amplification, library construction, sequencing and
subsequent bioinformatic analysis. Computational algorithms are essential to
fulfill many tasks of interest using scRNA-seq data. scRNA-seq has already
enabled researchers to revisit long-standing questions in cancer biology,
including cancer metastasis, heterogeneity and evolution. Circulating Tumor Cells
(CTC) are not only an important mechanism for cancer metastasis, but also provide
a possibility to diagnose and monitor cancer in a convenient way independent of
surgical resection of the cancer.
PMID- 29943296
TI - Super-Resolution Fluorescence Microscopy for Single Cell Imaging.
AB - In the past two decades, super-resolution fluorescence microscopy has undergone a
dynamic evolution. Following proof-of-concept studies with stimulated emission
depletion (STED) microscopy, several new approaches such as structured
illumination microscopy (SIM), photoactivation localization microscopy (PALM) and
stochastic optical reconstruction microscopy (STORM), have been developed for
imaging of nanoscale structural details and fast cellular dynamics in biological
research. In this chapter, after briefly explaining their principles, we will
describe the recent application of these super-resolution techniques in single
cell imaging. In addition, the extension of super-resolution microscopy to 3D,
multicolor, live-cell imaging and multimodal imaging are also discussed,
significantly improving the precision of single cell imaging. Combining with
molecular biology, biochemistry and bio-computing algorithms, super-resolution
fluorescence microscopy continues to expand its capabilities and provide
comprehensive insights into the details of single cells.
PMID- 29943297
TI - Single Cell Proteomics for Molecular Targets in Lung Cancer: High-Dimensional
Data Acquisition and Analysis.
AB - In the proteomic and genomic era, lung cancer researchers are increasingly under
challenge with traditional protein analyzing tools. High output, multiplexed
analytical procedures are in demand for disclosing the post-translational
modification, molecular interactions and signaling pathways of proteins
precisely, specifically, dynamically and systematically, as well as for
identifying novel proteins and their functions. This could be better realized by
single-cell proteomic methods than conventional proteomic methods. Using single
cell proteomic tools including flow cytometry, mass cytometry, microfluidics and
chip technologies, chemical cytometry, single-cell western blotting, the quantity
and functions of proteins are analyzed simultaneously. Aside from deciphering
disease mechanisms, single-cell proteomic techniques facilitate the
identification and screening of biomarkers, molecular targets and promising
compounds as well. This review summarized single-cell proteomic tools and their
use in lung cancer.
PMID- 29943298
TI - Therapeutic Antibody Discovery in Infectious Diseases Using Single-Cell Analysis.
AB - Since the discovery of mouse hybridoma technology by Kohler and Milstein in 1975,
significant progress has been made in monoclonal antibody production. Advances in
B cell immortalization and phage display technologies have generated a myriad of
valuable monoclonal antibodies for diagnosis and treatment. Technological
breakthroughs in various fields of 'omics have shed crucial insights into
cellular heterogeneity of a biological system in which the functional
individuality of a single cell must be considered. Based on this important
concept, remarkable discoveries in single-cell analysis have made in identifying
and isolating functional B cells that produce beneficial therapeutic monoclonal
antibodies. In this review, we will discuss three traditional methods of antibody
discovery. Recent technological platforms for single-cell antibody discovery will
be reviewed. We will discuss the application of the single-cell analysis in
finding therapeutic antibodies for human immunodeficiency virus and emerging Zika
arbovirus.
PMID- 29943299
TI - Single Cell Genetics and Epigenetics in Early Embryo: From Oocyte to Blastocyst.
AB - Single cell technology has enormously changed the landscape of biomedical
science, including single cell omics, gene editing, single cell imaging, single
cell (embryo) manipulate, or non-invasive micro-test. Single cell technology also
leads the research area of early embryo from basic research to reproductive
medical application. We got the knowledge of programming/reprogramming and the
epigenetics dynamics in the cell lineage differentiation. In the reproductive
medicine, the genomic sequencing of embryo or polar body and the preimplantation
genetic diagnosis rely on the single cell techniques. Those discoveries will
improve the assisted reproductive technologies, human health, and livestock
husbandry. In the future, the comprehensive atlas of cell state and lineage
information can be generated for cellular systems by single-cell multi-omics
approaches.
PMID- 29943300
TI - The Potential Roles and Advantages of Single Cell Sequencing in the Diagnosis and
Treatment of Hematological Malignancies.
AB - Hematological malignancies (HM) are a heterogeneous group of life-threatening
hematological diseases. The heterogeneity and clonal evolution of HM
subpopulations are the main obstacles for precise diagnoses, risk stratification,
and even targeted therapies. Standard bulk-sample genomic examinations average
total mutations from multiple subpopulations and conceal the clonal diversity
that may play a significant role in HM progression. Therefore, the development of
novel methods that detect intra-tumor heterogeneity is critical for the discovery
of novel potential therapeutic targets. The recently developed single cell
sequencing (SCS) technologies can analyse genetic polymorphisms at a single cell
level. SCS requires the precise isolation of single cells and amplification of
their genetic material. It allows the analysis of genomic, transcriptomic, and
epigenomic information in single cancer cells. SCS may also be able to monitor
minimal residual disease (MRD) of HM by sequencing circulating tumor cells (CTCs)
from peripheral blood. Functional heterogeneity and clonal evolution exist in
acute leukemia, multiple myeloma (MM) and chronic myeloid leukemia (CML)
subpopulations and have prognostic value. In this thesis, we provide an overview
of SCS technologies in HM and discuss the heterogeneous genetic variation and
clonal structure among subpopulations of HM. Furthermore, we aimed to shed light
on the clinical applications of SCS technologies, including the development of
new targeted therapies for drug-resistant or recurrent HM.
PMID- 29943301
TI - Application of Single Cell Sequencing in Cancer.
AB - Cancer is a heterogenetic disease at both the level of clinical manifestation and
the level of the genome. Single-cell sequencing provides an unprecedented means
of characterizing the intra-tumor heterogeneity and detecting and analyzing the
genomes of cancer cells. These data will help to reconstruct the understanding of
the evolutionary lineage of cancer cells. In the future, single-cell technology
is believed to be a useful tool in diagnostic and prognostic application in
oncology. The application of single cell technology in clinics will make it
possible to detect cancer non-invasively at early stages and to develop precision
medicine. In this chapter, we review the research and application status of the
single cell technology in cancer.
PMID- 29943302
TI - Emergence of Bias During the Synthesis and Amplification of cDNA for scRNA-seq.
AB - The advent of single-cell omics technology has promoted our understanding of the
genomic, epigenomic, and transcriptomic heterogeneity in individual cells.
Compared to traditional sequencing studies using bulk cells, single-cell
transcriptome technology is naturally more dynamic for in depth analysis of
genomic variation resulting from cell division and is useful in unraveling the
regulatory mechanisms of gene networks in many diseases. However, there are still
some limitations of current single-cell RNA sequencing (scRNA-seq) protocols.
Biases that arise during the RNA reverse transcription and cDNA pre-amplification
steps are the most common problems and play pivotal roles in limiting the
quantitative accuracy of scRNA-seq. In this review, we will describe how these
biases emerge and impact scRNA-seq protocols. Moreover, we will introduce several
current and convenient modified scRNA-seq methods that allow for bias to be
decreased and estimated.
PMID- 29943303
TI - Detection and Application of RNA Editing in Cancer.
AB - RNA editing is the process which happened in the post-transcriptional stage that
the genetic information contained in an RNA molecule will be changed. RNA editing
has been found to be related with many cancers, so through identifying RNA
editing sites, we can find useful information on the process of carcinogenesis.
In this review, we will discuss the main types of RNA editing and their role in
cancers, as well as the current detection methods of RNA editing and the
challenges we should overcome.
PMID- 29943304
TI - Is Pooled CRISPR-Screening the Dawn of a New Era for Functional Genomics.
AB - Functional genomics aims to develop an in-depth understanding of how specific
gene dysfunctions are related to diseases. A common method for investigating the
genome and its complex functions is via perturbation of the interactions between
the DNA, RNA and their protein respective protein derivatives. Commonly, arrayed
and pooled genetic screens are utilized to achieve this and in recent years have
been fundamental in achieving the current level of understanding for gene
dysfunctions. However, they are limited in specific aspects which scientists have
attempted to address. Clustered regularly palindromic repeats (CRISPR)-based
methods for genetic screens have in recent years become more prevalent but
crucially shared similar properties to previous methods and failing to provide a
distinct advantage over previous methods. CROP-seq, Perturb-seq, and CRISPR-seq
have combined CRISPR and single-cell RNA-sequencing (scRNA-seq) and is the newest
addition to the geneticist's arsenal, providing scientists with methods to edit
DNA with improved speed, accuracy, and efficiency which could usher us into a new
era of study methods for functional genomics. We briefly overview the CRISPR-Cas9
systems, the evolution of genetic screening in recent years, and evaluate and
discuss the significance of CROP-seq, Perturb-seq, and CRISPR-seq.
PMID- 29943305
TI - Roles of Single Cell Systems Biomedicine in Lung Diseases.
AB - Single cell sequencing is important to detect the gene heterogeneity between
cells, as the part of single-cell systems biology which combines computational
science, mathematical modelling and high-throughput technologies with biological
function and organization in the cell. We initially arise the question how to
integrate the outcomes of single-cell systems biology with clinical phenotype,
interpret alterations of single-cell gene sequencing and function in patient
response to therapies, and understand the significance of single-cell systems
biology in the discovery and development of new molecular diagnostics and
therapeutics. The present review furthermore focuses the significance of singe
cell systems biology in respiratory diseases and calls the special attention from
scientists who are working on single cell systems biology to improve the
diagnosis and therapy for patients with lung diseases.
PMID- 29943306
TI - The Significance of Single-Cell Biomedicine in Stem Cells.
AB - Clinical application of stem cells (SCs) progresses significantly in the
treatment of a large number of diseases, e.g. leukemia, respiratory diseases,
kidney disease, cerebral palsy, autism, or autoimmune diseases. Of those, the
population, biological phenotypes, and functions of individual SCs are mainly
concerned, due to the lack of cell separation and purification processes. The
single-cell technology, including microfluidic technology and single-cell genome
amplification technology, is widely used to study SCs and gains some
recognitions. The present review will address the importance of single-cell
technologies in the recognition and heterogeneity of SCs and highlight the
significance of current single-cell approaches in the understanding of SC
phenotypes. We also discuss the values of single-cell studies to overcome the
bottleneck in explore of biological mechanisms and reveal the therapeutic
potentials of SCs in diseases, especially tumor-related diseases, as new
diagnostic and therapeutic strategies.
PMID- 29943307
TI - The low levels of bone morphogenic protein-4 and its antagonist noggin in type 2
diabetes.
AB - OBJECTIVE: Bone morphogenic protein-4 (BMP-4) is a proinflammatory cytokine which
is controlled by BMP-4 antagonists. Our aim was to investigate the levels of BMP
4 and its antagonists, noggin and matrix Gla protein (MGP), in prediabetes and
diabetes. DESIGN: One hundred and forty-two type 2 diabetic, 32 prediabetic, and
58 control subjects participated in this cross-sectional study. BMP-4, noggin,
and MGP were measured with the ELISA method. RESULTS: There was a significant
difference between the three groups in relation to sex, hypertension, fasting
plasma glucose, HbA1c, lipid profiles, and diastolic blood pressure (p < 0.05).
BMP-4 levels were significantly lower in the diabetic group compared to the
control group (108.5 and 127.5 ng/mL, respectively, p < 0.001 diabetes vs.
control). Noggin levels were significantly lower in the diabetic group compared
to the prediabetic and control groups (10.5, 11.5, and 12.0 ng/mL, as median,
respectively, p < 0.001; diabetes vs. control, p = 0.002; diabetes vs.
prediabetes). BMP-4 was associated significantly with noggin in the entire study
population (beta coefficient = 0.796, p < 0.001). Receiver operating
characteristic (ROC) curve analysis showed that the area under the ROC curve was
0.708 (95% CI 0.551-0.864, p = 0.011) for BMP-4 levels. The optimal cutoff value
of BMP-4 for detecting albuminuria was 118.5 ng/mL for which sensitivity was
71.4% and specificity was 66.4%. CONCLUSIONS: BMP-4 and noggin levels were lower
in the diabetic group. High BMP-4 levels were significantly associated with
albuminuria. Further studies are warranted to determine the role of BMP-4 in the
pathogenic processes underlying albuminuria and hyperglycemia in patients with
type 2 diabetes.
PMID- 29943308
TI - Detection of MRSA in nasal swabs-marked reduction of time to report for negative
reports by substituting classical manual workflow with total lab automation.
AB - In 2016, the workflow for MRSA detection in nasal swabs was changed from a
classic-manual workflow to an automated workflow using total lab automation (TLA;
BD Kiestra). This change entailed a reduction of the incubation time from 2 days
to 20 h and reading of plates on weekdays and weekends instead of weekdays only.
The workflow alteration did not include the introduction of 24/7. We wanted to
follow up on the consequences for the times to report (TTR). We compared the TTR
of all nasal swabs, which were sent for MRSA detection from June until August in
2015 (workflow-classic-manual) and in 2016 (workflow-automated). We calculated
median TTR and interquartile ranges for the three possible reporting outcomes
(negative, MRSA-known, MRSA-new) per day and workflow. A multivariable linear
regression modeled the exposure variables workflow, day, and reporting outcome on
TTR including interaction variables. The quantity and reasons for a TTR longer
than 3 days were analyzed. During both 3-month periods, a total of 16,111 reports
were issued (2015:7620; 2016:8491). The median TTR for negative reports was 48:28
(hh:mm) in 2015 and 23:58 in 2016. In the linear regression, all exposure
variables had a strong and highly significant (p < 0.001) influence on the TTR.
The number of reports with a TTR longer than 3 days shrank from 2418 (2015) to 60
(2016). The workflow alteration halved the median TTR for negative reports and
the number of reports with a TTR longer than 3 days was reduced by 97.5%.
PMID- 29943309
TI - Radioiodine (131I) therapies performed in a paediatric hospital: facilities and
procedures.
AB - Radioiodine (131I) therapies on younger children with thyroid cancer and
neuroblastoma can be challenging as they are required to be isolated for a period
of time due to radiation safety concerns. At our hospital these therapies are
performed in a purpose-built child-friendly therapy room. Nursing staff are able
to provide personal care during the isolation period with minimum radiation
exposure. Patients are provided with various age-appropriate entertainment items
such as iPad, X-Box, DVD, craft and books to keep them entertained while in
isolation. Parents can communicate freely with their child via the audio-visual
system located in the Ward Parent Lounge and can also stay in the shielded part
of the ante room of the therapy room. Nursing staff can communicate with the
patient via a similar audio-visual system located in the nurses station so that
they only need to enter the therapy room when they are required to provide
personal patient care. All persons entering the therapy room are monitored with
personal digital dosimeters. Patients accept the isolation period with minimal
aggravation and the personal radiation exposures to staff, parents and visitors
are well below the general public annual limit of 1000 uSv. The design and
facilities of the therapy room with its child-friendly surroundings and support
network makes the experience of the isolation period easier and positive for both
patients and parents. For Graves' disease, the patients are treated as
outpatients in the Department of Nuclear Medicine and are discharged within a
short time after the radioiodine administration.
PMID- 29943310
TI - The peripheral dose outside the applicator in electron beams of an Elekta linear
accelerator.
AB - Peripheral doses out of field could have short and long terms biological effects
on patients treated with electron beams. In this study, peripheral dose outside
the applicator was measured using the 6, 10 and 18 MeV beams of an Elekta synergy
linac. For these beams dose profiles were measured using EBT3 film at various
depths within a solid water phantom. Measurements were performed using 6 * 6, 10
* 10, 14 * 14 and 20 * 20 cm2 applicators at gantryangles of 0 degrees , 10
degrees and 20 degrees and depths of 0, 0.5, 1 cm and depth of Dmax (maximum
dose) for each energy. The peripheral dose profiles were normalized to the
distance of 2 cm from the edge of each field. The largest peak of the peripheral
dose was observed for 18 MeV 3 cm from the outer edge of the applicator. Peak
dose increased with increasing energy. Peak dose at 18 MeV electron beam was 1.6%
at the surface of phantom and at the distance of 2 cm from the outer edge of the
applicator when the applicator of 20 * 20 cm2 was used. Peak dose at 6 MeV
electron beam was 1.15% at the same distance in the same applicator size. It was
found that the peak dose decreased with increasing depth and increased with
increase in field size. Also, the peak dose moved towards CAX with increase in
gantry angle.In general dose to tissue out of field could be reduced using
appropriate shielding for each applicator and beam energy.
PMID- 29943311
TI - Future forum, Hobart, October 29, 2017: examining the role of medical physics in
cancer research.
AB - This commentary reports on a forum held in October 2017 in Hobart, Tasmania,
attended by 20 Australasian medical physicists, to consider the future role of
medical physics, as well as non-medical physics and allied disciplines, in
oncology research. Attendees identified important areas of oncology research
which physicists can be contributing to, with these evaluated in the context of a
set of "Provocative Questions" recently generated by the American Association of
Physicists in Medicine. Primary perceived barriers to participation in research
were identified, including a "lack of knowledge of cancer science", together with
potential solutions. Mechanisms were considered for engagement with the broader
scientific community, consumers, advocates and policy makers. In considering
future opportunities in oncology research for medical physicists, it was noted
that a professional need to focus on the safety and accuracy of current
treatments applied to patients, encouraging risk-aversion, is somewhat in
competition with the role of physical scientists in the exploration and discovery
of new concepts and understandings.
PMID- 29943312
TI - Biomechanical behavior of Hoffa's fat pad in healthy and osteoarthritic
conditions: histological and mechanical investigations.
AB - The Infrapatellar Fat Pad (IFP) lies between patella, femur, meniscus and tibia
and properly fills the space between these structures. This fatty structure
facilitates distribution of synovial fluid and may act to absorb impulsive
actions generated through the joint. In case of Osteoarthritis (OA), IFP is found
to be affected by inflammation, hypertrophy and fibrosis. The aim of the present
study is to analyze the correlation between microscopic characteristics and
mechanical properties of the IFP in healthy and OA conditions. The microscopic
anatomy of the IFP was analyzed through histological methods, whose results
showed that the IFP affected by OA maintains similar lobules configuration but
thicker interlobular septa. Geometrical data together with the morphological
analysis of lobules and septa represented the basic data to provide numerical
micro-models of the IFP. Numerical analyses were developed to evaluate the
mechanical behavior considering the characteristic loading conditions as
compressive, torsion and shear actions. The results were applied to identify the
parameters of a homogenized hyperelastic constitutive formulation that interprets
the IFP mechanics. The constitutive formulation was implemented within a finite
element model of the knee, which was applied to evaluate the overall mechanical
functionality of the knee structures. The results pointed out the actual
mechanical relevance of IFP and the loss of proper stress-strain behavior of the
OA IFP under mechanical loads.
PMID- 29943314
TI - The Contribution of the Reciprocal-Engagement Model as a Theoretical Framework of
a Portuguese Scale for Quality Assessment of Genetic Counseling.
PMID- 29943313
TI - 18F-FDG PET/CT can predict chemosensitivity and proliferation of epithelial
ovarian cancer via SUVmax value.
AB - PURPOSE: This study aimed to explore the clinical and prognostic significance of
18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography
(18F-FDG PET/CT) in epithelial ovarian cancer (EOC). METHODS: We retrospectively
investigated 48 EOC patients who underwent preoperative 18F-FDG PET/CT and
primary cytoreductive surgery at our hospital between January 2010 and June 2015.
None of these patients received neoadjuvant chemotherapy. PET/CT parameters
including the maximum and average standardized uptake value (SUVmax, SUVavg), the
metabolic tumor volume (MTV) were measured. Tumor proliferation marker Ki67 was
evaluated using immunohistochemistry. The relationships between the PET/CT
parameters and chemosensitivity, tumor proliferation, and overall survival (OS)
were analyzed, respectively. RESULTS: The median (range) SUVmax, SUVavg, and MTV
values were 11.42 (3.14-20.20), 4.8 (2.55-9.47), and 150.11 (0.19-792.46),
respectively. Overall, 93.8% (45/48) of patients had high-grade serous ovarian
cancer. The SUVmax value had a positive correlation with the Ki67 index (P =
0.030, r = 0.314), and a higher SUVmax level was associated with chemosensitivity
(P = 0.026). However, neither SUVavg nor MTV had associations with the patients'
clinicopathological parameters. None of these three PET/CT parameters were found
to be potential predictors of OS. CONCLUSIONS: Preoperative 18F-FDG PET/CT had a
predictive value on chemosensitivity and proliferation after primary debulking
surgery in EOC patients noninvasively.
PMID- 29943315
TI - Genomic Selection Using BayesCpi and GBLUP for Resistance Against Edwardsiella
tarda in Japanese Flounder (Paralichthys olivaceus).
AB - The Japanese flounder is one of the most widely farmed economic flatfish species
throughout eastern Asia including China, Korea, and Japan. Edwardsiella tarda is
a major species of pathogenic bacteria that causes ascites disease and,
consequently, a huge economy loss for Japanese flounder farming. After generation
selection, traditional breeding methods can hardly improve the E. tarda
resistance effectively. Genomic selection is an effective way to predict the
breeding potential of parents and has rarely been used in aquatic breeding. In
this study, we chose 931 individuals from 90 families, challenged by E. tarda
from 2013 to 2015 as a reference population and 71 parents of these families as
selection candidates. 1,934,475 markers were detected via genome sequencing and
applied in this study. Two different methods, BayesCpi and GBLUP, were used for
genomic prediction. In the reference population, two methods led to the same
accuracy (0.946) and Pearson's correlation results between phenotype and genomic
estimated breeding value (GEBV) of BayesCpi and GBLUP were 0.912 and 0.761,
respectively. In selection candidates, GEBVs from two methods were highly similar
(0.980). A comparison of GEBV with the survival rate of families that were
structured by selection candidates showed correlations of 0.662 and 0.665,
respectively. This study established a genomic selection method for the Japanese
flounder and for the first time applied this to E. tarda resistance breeding.
PMID- 29943316
TI - Part II: Temporomandibular Joint (TMJ)-Regeneration, Degeneration, and
Adaptation.
AB - PURPOSE OF REVIEW: Elucidate temporomandibular joint (TMJ) development and
pathophysiology relative to regeneration, degeneration, and adaption. RECENT
FINDINGS: The pharyngeal arch produces a highly conserved stomatognathic system
that supports airway and masticatory function. An induced subperiosteal layer of
fibrocartilage cushions TMJ functional and parafunctional loads. If the
fibrocartilage disc is present, a fractured mandibular condyle (MC) regenerates
near the eminence of the fossa via a blastema emanating from the medial
periosteal surface of the ramus. TMJ degenerative joint disease (DJD) is a
relatively painless osteoarthrosis, resulting in extensive sclerosis, disc
destruction, and lytic lesions. Facial form and symmetry may be affected, but the
residual bone is vital because distraction continues to lengthen the MC with
anabolic bone modeling. Extensive TMJ adaptive, healing, and regenerative
potential maintains optimal, life support functions over a lifetime. Unique
aspects of TMJ development, function, and pathophysiology may be useful for
innovative management of other joints.
PMID- 29943317
TI - Behavior of two Leishmania infantum strains-evaluation of susceptibility to
antimonials and expression of microRNAs in experimentally infected J774
macrophages and in BALB/c mice.
AB - Strains of the same Leishmania parasite species, isolated from different host
organisms, may exhibit unique infection profiles and induce a change in the
expression of microRNAs among host macrophages and in model host mice. MicroRNAs
(MiR) are endogenous molecules of about 22 nucleotides that are involved in many
regulatory processes, including the vertebrate host immune response. In this
respect, the infectivity and susceptibility to antimonials of two L. infantum
strains, BH46, isolated from human, and OP46, isolated from symptomatic dog, were
characterized in J774 macrophages and BALB/c mice. Parasite burden was assessed
in the liver, spleen, and bone marrow using the serial limiting dilution
technique. A higher parasite burden was observed in the spleen and bone marrow of
animals infected with OP46 compared to BH46 strain. Our results also showed that
OP46 was less susceptible to the antimonials. In addition, miR-122 and miR-155
expression was evaluated in the liver and J774 macrophages, and in spleens from
infected animals, respectively. An increase was observed in the expression of miR
155 in J774 macrophages infected with both strains compared to uninfected cells,
with a higher expression in cells infected with OP46. However, no difference in
the expression of miR-122 and miR-155 was observed in the infected animals. Thus,
this study shows that OP46 was more infective for mice, it caused a higher
increase in miR-155 expression in infected macrophages and was less susceptible
to the antimonials evaluated. These data suggest that alteration in miR-155 level
likely plays a role in regulating the response to L. infantum.
PMID- 29943318
TI - Molecular investigation of vector-borne parasites in wild micromammals, Barcelona
(Spain).
AB - Information about the role of micromammals in the epidemiology of Leishmania
infantum and Babesia sp. in southern Europe is scarce. Wild micromammals were
captured in natural areas in the Barcelona province (NE Spain) in 2011 and
analysed by real-time PCR for the presence of DNA of Piroplasmida (n = 253) and
Leishmania infantum (n = 166). The wood mouse (Apodemus sylvaticus) was the most
abundant species, but all specimens tested negative for L. infantum, for which
two out of 15 (13.3%) white-toothed shrews (Crocidura russula) and one out of 23
(4.3%) Algerian mice (Mus spretus) resulted positive. No individual was positive
for Piroplasmida DNA. The role of wild micromammals in the epidemiology of these
parasites in the study area seems negligible.
PMID- 29943321
TI - ?
PMID- 29943320
TI - Melatonin and ST Segment Elevation Acute Myocardial Infarction-the "Forgotten
Cardioprotective Therapy" Strikes Again.
PMID- 29943322
TI - ?
PMID- 29943323
TI - ?
PMID- 29943319
TI - The utility of an rTeGM6-4r-based immunochromatographic test for the serological
diagnosis of non-tsetse-transmitted equine trypanosomosis in rural areas of
Mongolia.
AB - Our previous studies report epidemics of non-tsetse-transmitted equine
trypanosomosis in Mongolia. However, the current status of non-tsetse-transmitted
equine trypanosomosis endemicity remains to be clarified in some parts of
Mongolia. We previously reported the potential application of rTeGM6-4r-based
diagnostic tools, an rTeGM6-4r-based immunochromatographic test (ICT) and an
enzyme-linked immunosorbent assay (ELISA), in the serological surveillance of
equine trypanosomosis in Mongolia. In the present study, the utility of the
rTeGM6-4r-based ICT was validated. The rTeGM6-4r-based ICT accurately diagnosed
positive reference sera that had been prepared from dourine horses in Mongolia,
similarly to the rTeGM6-4r-based ELISA. The diagnostic performance of the rTeGM6
4r-based ICT was maintained when the strips were preserved for at least 2 months
under dry conditions. The ICT detected 42 positive serum samples from a total of
1701 equine sera that had been collected from all 21 provinces of Mongolia. The
kappa-value, sensitivity and specificity of rTeGM6-4r-based ICT were 0.58, 50.0%
(95% CI, 37.7-62.3%) and 99.3% (95% CI, 98.7-99.6%), respectively, in comparison
to the rTeGM6-4r-based ELISA. Our field-friendly rTeGM6-4r-based ICT was found to
be useful for the serological diagnosis of non-tsetse-transmitted equine
trypanosomosis in rural areas of Mongolia.
PMID- 29943324
TI - ?
PMID- 29943325
TI - ?
PMID- 29943326
TI - ?
PMID- 29943327
TI - [Famous people living with HIV and AIDS].
PMID- 29943328
TI - [Long-Term Non-Progressor].
PMID- 29943329
TI - [Generic antiretroviral drugs and their potential for cost reduction].
PMID- 29943330
TI - [Are there strategies against latent infection?]
PMID- 29943331
TI - [The HIV reservoir in resting CD4 T-cells: Barrier on the road to an HIV cure].
PMID- 29943332
TI - [The cure of Timothy Brown. How is his condition now and has this case been
repeated?]
PMID- 29943333
TI - [Is there still hope for an HIV vaccine?]
PMID- 29943334
TI - [New opportunities for HIV diagnostics].
PMID- 29943335
TI - [Professional HIV testing].
PMID- 29943336
TI - ?
PMID- 29943337
TI - ?
PMID- 29943338
TI - ?
PMID- 29943339
TI - ?
PMID- 29943340
TI - ?
PMID- 29943341
TI - ?
PMID- 29943342
TI - ?
PMID- 29943343
TI - ?
PMID- 29943346
TI - ?
PMID- 29943344
TI - ?
PMID- 29943347
TI - Complicated Acute Heart Failure Subsets.
PMID- 29943348
TI - Spanish Language Use Across Generations and Depressive Symptoms Among US Latinos.
AB - Acculturation markers, such as language use, have been associated with Latino
depression. Language use may change between generations; however, few studies
have collected intergenerational data to assess how language differences between
generations impact depression. Using the Ninos Lifestyle and Diabetes Study (2013
2014), we assessed how changes in Spanish language use across two generations of
Mexican-origin participants in Sacramento, California, influenced offspring
depressive symptoms (N = 603). High depressive symptoms were defined as CESD-10
scores >= 10. We used log-binomial and linear-binomial models to calculate
prevalence ratios and differences, respectively, for depressive symptoms by
language use, adjusting for identified confounders and within-family clustering.
Decreased Spanish use and stable-equal English/Spanish use across generations
protected against depressive symptoms, compared to stable-high Spanish use.
Stable-low Spanish use was not associated with fewer depressive symptoms compared
to stable-high Spanish use. Exposure to multiple languages cross-generationally
may improve resource access and social networks that protect against depression.
PMID- 29943349
TI - Residual Dipolar Couplings in Structure Determination of Natural Products.
AB - The determination of natural products stereochemistry remains a formidable task.
Residual dipolar couplings (RDCs) induced by anisotropic media are a powerful
tool for determination of the stereochemistry of organic molecule in solution.
This review will provide a short introduction on RDCs-based methodology for the
structural elucidation of natural products. Special attention is given to the
current availability of alignment media in organic solvents. The applications of
RDCs for structural analysis of some examples of natural products were discussed
and summarized. This review provides a short introduction on RDCs-based
methodology for the structural elucidation of natural products. Special attention
is given to the current availability of alignment media in organic solvents. The
applications of RDCs for structural analysis of some examples of natural products
were discussed and summarized.
PMID- 29943350
TI - Total bleeding with rivaroxaban versus warfarin in patients with atrial
fibrillation receiving antiplatelet therapy after percutaneous coronary
intervention.
AB - : Among atrial fibrillation (AF) patients undergoing percutaneous coronary
intervention (PCI), rivaroxaban with background antiplatelet therapy
significantly reduced the first occurrence of bleeding compared to triple therapy
with warfarin. This study hypothesized that total bleeding events, including
those beyond the first event, would be reduced with rivaroxaban-based regimens.
In the PIONEER AF-PCI trial, 2099 patients in the modified intention-to-treat
population were randomized to three groups and followed for 12 months: (1)
rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (N = 696); (2) rivaroxaban
2.5 mg twice daily plus dual antiplatelet therapy (DAPT) (N = 706); and (3) dose
adjusted warfarin plus DAPT (N = 697). Descriptive statistics for the number of
subjects who experienced one or more bleeding events were calculated. The total
number of bleeding events was compared across treatment groups using the Wei,
Lin, and Weissfeld method. A total of 514 and 439 events of clinically
significant bleeding and bleeding requiring medical attention occurred throughout
the study. Compared to triple therapy with warfarin, rivaroxaban-based regimen
was associated with a reduction in total events of clinically significant
bleeding (Group 1 vs. Group 3: HR 0.64 [95% CI 0.49-0.85], p < 0.001, NNT = 11;
Group 2 vs. Group 3: HR 0.62 [95% CI 0.48-0.80], p < 0.001, NNT = 10). Similarly,
rivaroxaban reduced the total bleeding events requiring medical attention (Group
1 vs. Group 3: HR 0.66 [95% CI 0.49-0.89], p < 0.001, NNT = 14; Group 2 vs. Group
3: HR 0.64 [95% CI 0.48-0.85], p = 0.002, NNT = 13). Rivaroxaban-based regimen
reduced the total bleeding events compared with VKA-based triple therapy in
stented AF patients. One clinically significant bleeding event could be prevented
with rivaroxaban use for every 10-11 patients treated, and one bleeding requiring
medical attention could be prevented with rivaroxaban for every 13-14 patients
treated. These data provide evidence that total bleeding events, including those
beyond the first event, are reduced with rivaroxaban-based antithrombotic
regimens. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov .
Unique identifier: NCT01830543 (PIONEER AF-PCI).
PMID- 29943352
TI - The Effects of Deferred Action for Childhood Arrivals on the Educational Outcomes
of Undocumented Students.
AB - Deferred Action for Childhood Arrivals (DACA) is the first large-scale
immigration policy to affect undocumented immigrants in the United States in
decades and offers eligible undocumented youth temporary relief from deportation
as well as renewable work permits. Although DACA has improved the economic
conditions and mental health of undocumented immigrants, we do not know how DACA
improves the social mobility of undocumented immigrants through its effect on
educational attainment. We use administrative data on students attending a large
public university to estimate the effect of DACA on undocumented students'
educational outcomes. The data are unique because they accurately identify
students' legal status, account for individual heterogeneity, and allow separate
analysis of students attending community colleges versus four-year colleges.
Results from difference-in-difference estimates demonstrate that as a temporary
work permit program, DACA incentivizes work over educational investments but that
the effect of DACA on educational investments depends on how easily colleges
accommodate working students. At four-year colleges, DACA induces undocumented
students to make binary choices between attending school full-time and dropping
out of school to work. At community colleges, undocumented students have the
flexibility to reduce course work to accommodate increased work hours. Overall,
the results suggest that the precarious and temporary nature of DACA creates
barriers to educational investments.
PMID- 29943351
TI - Lights and shadows of long-term dual antiplatelet therapy in "real life" clinical
scenarios.
AB - Dual antiplatelet therapy (DAPT) is a cornerstone of treatment for patients with
acute coronary syndromes (ACS). Mounting evidences have opened the debate about
the optimal DAPT duration. Considering the ACS-pathophysiology, the most recent
guidelines recommend DAPT in all ACS patients for at least 12 months unless there
are contraindications such as excessive risk of bleeding. Thus, it can be
considered acceptable earlier discontinuation if the risk of morbidity from
bleeding outweighs the anticipated benefit. On the other hand, several studies
have clearly indicated that a significant burden of platelet related-events, such
as stroke and new ACS might occur after this period, suggesting that potential
benefits might derive by prolonging DAPT beyond 12 months (Long DAPT). Indeed,
although current guidelines give some indications about patients eligible for
Long DAPT, they do not embrace several real-life clinical scenarios. Thus, in
such scenarios, how to decide whether a patient is eligible for Long DAPT or not
might be still challenging for clinicians. This position paper presents and
discusses various "real-life" clinical scenarios in ACS patients, in order to
propose several possible recommendations to overcome guidelines potential
limitations.
PMID- 29943353
TI - Imputation Match Bias in Immigrant Wage Convergence.
AB - Although immigrants to the United States earn less at entry than their native
born counterparts, an extensive literature has found that immigrants have faster
earnings growth that results in rapid convergence to native-born earnings.
However, recent evidence based on U.S. Census data indicates a slowdown in the
rate of earnings assimilation. We find that the pace of immigrant wage
convergence based on recent data may be understated in the literature as a result
of the method used by the census to impute missing information on earnings, which
does not use immigration status as a match characteristic. Because both the share
of immigrants in the workforce and earnings imputation rates have risen over
time, imputation match bias for recent immigrants is more consequential than in
earlier periods and may lead to an underestimate of the rate of immigrant wage
convergence.
PMID- 29943354
TI - VPA selectively regulates pluripotency gene expression on donor cell and improve
SCNT embryo development.
AB - SCNT technology has been successfully used to clone a variety of mammals, but the
cloning efficiency is very low. This low efficiency is likely due to the
incomplete reprogramming of SCNT embryos. Histone modification and DNA
methylation may participate in these events. Thus, it would be interesting to
attempt to improve the efficiency of SCNT by using a HDACi VPA. In order to
guarantee the effect of VPA and reduce its cytotoxicity, a comprehensive analysis
of the cell proliferation and histone modification was performed. The results
showed that 0.5 and 1 mM VPA treatment for 24 h were the optimal condition.
According to the results, H3K4me3 was increased in 0.5 and 1 mM VPA groups,
whereas H3K9me2 was significantly decreased. These are the signals of gene
activation. In addition, VPA treatment led to the overexpression of Oct4 and
Nanog. These indicated that VPA-treated cells had similar patterns of histone to
zygotic embryos, and may be more favorable for reprograming. A total of 833
cloned embryos were produced from the experimental replicates of VPA-treated
donor cells. In 1 mM treatment group, the blastocyst rates were significantly
increased compared with control. At the same time, our findings demonstrated the
interrelation between DNA methylation and histone modifications.
PMID- 29943355
TI - Establishment and characterization of novel patient-derived osteosarcoma
xenograft and cell line.
AB - Osteosarcoma is an aggressive mesenchymal malignancy of the bone. Patient-derived
models are essential tools for elucidating the molecular mechanisms associated
with poor prognosis and the development of novel anticancer drugs. This study
described the establishment of a patient-derived cancer model of osteosarcoma.
Primary osteosarcoma tumor tissues were obtained from an osteosarcoma patient and
inoculated in the skin of immunodeficient mice, followed by transplantation to
other mice upon growth. Cells were maintained in monolayer cultures, and the
capability of spheroid formation was assessed by seeding the cells on culture
dishes. The invasion ability of cells was monitored by Matrigel assay, and
genomic and proteomic backgrounds were examined by mass spectrometry. A cell line
was established from patient-derived tumors and showed similar histology to that
of the primary tumor tissue. Additionally, these cells formed spheroids on low
attachment tissue-culture dishes and exhibited invasive capabilities, and we
confirmed that the genomic backgrounds were similar between patient-derived
xenograft tumors and the cell line. Furthermore, the proteome of the patient
derived tumors and the cells exhibited similar, but not identical, patterns to
that of the original tumor tissue. Our results indicated that this patient
derived xenograft model and cell line would be useful resources for osteosarcoma
research.
PMID- 29943356
TI - Brain metastases in colorectal cancer: prognostic factors and survival analysis.
AB - PURPOSE: Colorectal cancer (CRC) brain metastases (BM) are an uncommon and late
event. We aim to investigate the impact of clinical factors, treatment modalities
and RAS/BRAF status on the outcomes of CRC patients with BM. PATIENTS: We
retrospectively analysed CRC patients who developed BM in our centre between
January 1997 and June 2017. Clinical factors, treatment modalities, RAS/BRAF
status and survival were evaluated. RESULTS: Twenty-eight patients were recorded;
82% had left-sided (LS) CRC and 71% had lung metastases. Median time to BM
diagnosis was 36 months (m) and 93% of patients received local treatment of BM
(43% whole brain radiotherapy, 50% surgery). Right-sided (RS) CRC showed shorter
time to BM, not previously described (9.3 vs 46.6 m for RS and LS CRC,
respectively; HR = 4.7, p = 0.006). Median overall survival (mOS) from BM
treatment was 9.5 m, better in patients who underwent surgery than those treated
with radiotherapy alone (12.1 vs 4.6 m, respectively; HR = 0.3, p = 0.019) and in
those without progressive metastatic extracranial disease (7.2 vs 20.9 m, for
progressive and non-progressive, respectively; HR = 0.3, p = 0.056). Patients
with two or more metastatic extracranial locations showed worse prognosis (5.9 vs
16.3 m, for > 2 vs 0-1, respectively; HR = 3.7, p = 0.015). RAS/BRAF status did
not showed prognostic value. CONCLUSIONS: Time to BM diagnosis is shorter in RS
CRC. The presence of two or more metastatic extracranial locations and
progressive metastatic extracranial disease at the time of BM diagnosis could be
bad prognosis factors for CRC BM patients.
PMID- 29943357
TI - High Circulatory Phosphate Level Is Associated with Cerebral Small-Vessel
Diseases.
AB - High phosphate is linked to vascular calcification and endothelial dysfunction;
however, its relationship with cerebral small-vessel diseases (CSVDs) is still
unknown. Study subjects were prospectively recruited from the community-based I
Lan Longitudinal Aging Study. CSVDs including lacunes, white matter
hyperintensities (WMHs), and cerebral microbleeds were evaluated using 3T
magnetic resonance images. Multivariate analyses were performed to study the
associations between circulatory phosphate level and the presence of CSVDs. In
vitro experiments included human brain microvascular endothelial cell (HBMEC)
studies and western blotting. The present study included 186 subjects (age [mean
+/- standard deviation, range] 64.7 +/- 8.6, 50-86.8 years; 93 men). Multivariate
analysis revealed that circulatory phosphate levels > 3.925 mg/dL were associated
with severe WMH with an odds ratio of 3.7 (95% confidence interval = 1.3-10.6)
independent of age, sex, traditional vascular risk factors, total cholesterol,
renal function, or circulatory calcium level. The in vitro study revealed a
downregulation of tight junction protein (zona occludens-1, occludin, and claudin
5) expression in HBMECs after 48 h of treatment with high phosphate (2.5/5 mM).
We are the first to report a relationship between circulatory phosphate and
CSVDs. Our results suggest that high circulatory phosphate level might be a novel
risk factor for CSVD, possibly by impairing BBB structures.
PMID- 29943358
TI - Hypertension and Organ Damage in Women.
AB - An adequate cardiovascular (CV) prevention strategy in women should consider the
acknowledgement of sex-specific risk factors, such as hypertension in pregnancy,
the concomitant presence of autoimmune diseases and the benefit of evaluating
subclinical organ damage and treating hypertension. In accordance to current
guidelines, the diagnostic approach does not differ between men and women,
although the cardiac response to pressure overload may suggest greater
sensitivity in women, and may vary according to age, ethnic background and
obesity, that potentiates the effect of hypertension on left ventricular (LV)
hypertrophy. Several studies have observed peculiar abnormalities in LV systolic
and diastolic function according to gender. The possible mechanisms that
influence a different cardiac adaptation to chronic pressure overload in men and
women are not fully understood, although hormonal status, and in particular the
lack of estrogen effects after menopause may contribute to the cardiovascular
adaptation response to increased afterload. The increase in LV mass in response
to chronic pressure overload is associated with higher LV ejection fraction in
women than in men and LV torsion is maintained with aging in women but not in
men. Interstitial fibrosis may reduce circumferential shortening and early
diastolic strain rate, in the presence of a preserved ejection fraction in women,
favoring the development of heart failure with preserved ejection fraction.
Changes in aortic stiffness with aging may influence cardiac structural and
functional changes. Isolated systolic hypertension reflects an increase in aortic
stiffness, is frequent in women and may be associated to a greater development of
concentric LVH. The regression of hypertensive LVH is more difficult in women,
and residual hypertrophy is more common in women than in men despite effective
antihypertensive treatment and blood pressure control. Carotid atherosclerosis
has been extensively investigated in men and women, showing that women usually
develop carotid plaques after menopause, with smaller and less unstable plaques;
however large and/or a hypoechogenic plaques are more strictly related to
cerebrovascular events in women than in men. More advanced abnormalities in the
subcutaneous microcirculation have been recently observed, and well translate in
the evidence of more prevalent coronary microcirculation involvement in women
ischemic heart disease. The prevalence of albuminuria and of reduced estimated
glomerular filtration rate (eGFR < 60 ml/min/1.73) are respectively lower and
higher in postmenopausal women than in men. Experimental data suggest the
possible involvement of renin-angiotensin-aldosterone system and of T regulatory
lymphocytes to this regard.
PMID- 29943360
TI - Characterization of cyanobacterial cells synthesizing 10-methyl stearic acid.
AB - Recently, microalgae have attracted attention as sources of biomass energy.
However, fatty acids from the microalgae are mainly unsaturated and show low
stability in oxygenated environments, due to oxidation of the double bonds. The
branched-chain fatty acid, 10-methyl stearic acid, is synthesized from oleic acid
in certain bacteria; the fatty acid is saturated, but melting point is low. Thus,
it is stable in the presence of oxygen and is highly fluid. We previously
demonstrated that BfaA and BfaB in Mycobacterium chlorophenolicum are involved in
the synthesis of 10-methyl stearic acid from oleic acid. In this study, as a
consequence of the introduction of bfaA and bfaB into the cyanobacterium,
Synechocystis sp. PCC 6803, we succeeded in producing 10-methyl stearic acid,
with yields up to 4.1% of the total fatty acid content. The synthesis of 10
methyl stearic acid in Synechocystis cells did not show a significant effect on
photosynthetic activity, but the growth of the cells was retarded at 34 degrees
C. We observed that the synthesis of 10-methylene stearic acid, a precursor of 10
methyl stearic acid, had an inhibitory effect on the growth of the transformants,
which was mitigated under microoxic conditions. Eventually, the amount of 10
methyl stearic acid present in the sulfoquinovosyl diacylglycerol and
phosphatidylglycerol of the transformants was remarkably higher than that in the
monogalactosyldiacylglycerol and digalactosyldiacylglycerol. Overall, we
successfully synthesized 10-methyl stearic acid in the phototroph, Synechocystis,
demonstrating that it is possible to synthesize unique modified fatty acids via
photosynthesis that are not naturally produced in photosynthetic organisms.
PMID- 29943359
TI - Complementary chromatic and far-red photoacclimations in Synechococcus ATCC 29403
(PCC 7335). I: The phycobilisomes, a proteomic approach.
AB - Synechococcus ATCC 29403 (PCC 7335) is a unicellular cyanobacterium isolated from
Puerto Penasco, Sonora Mexico. This cyanobacterium performs complementary
chromatic acclimation (CCA), far-red light photoacclimation (FaRLiP), and
nitrogen fixation. The Synechococcus PCC 7335 genome contains at least 31 genes
for proteins of the phycobilisome (PBS). Nine constitutive genes were expressed
when cells were grown under white or red lights and the resulting proteins were
identified by mass spectrometry in isolated PBS. Five inducible genes were
expressed under white light, and phycoerythrin subunits and associated linker
proteins were detected. The proteins of five inducible genes expressed under red
light were identified, the induced phycocyanin subunits, two rod linkers and the
rod-capping linker. The five genes for FaRLiP phycobilisomes were expressed under
far-red light together with the apcF gene, and the proteins were identified by
mass spectrometry after isoelectric focusing and SDS-PAGE. Based on in silico
analysis, Phylogenetic trees, and the observation of a highly conserved amino
acid sequence in far-red light absorbing alpha allophycoproteins encoded by
FaRLiP gene cluster, we propose a new nomenclature for the genes. Based on a
ratio of ApcG2/ApcG3 of six, a model with the arrangement of the allophycocyanin
trimers of the core is proposed.
PMID- 29943361
TI - Developmental regulation of protein import into plastids.
AB - The plastid proteome changes according to developmental stages. Accruing evidence
shows that, in addition to transcriptional and translational controls, preprotein
import into plastids is also part of the process regulating plastid proteomes.
Different preproteins have distinct preferences for plastids of different
tissues. Preproteins are also divided into at least three age-selective groups
based on their import preference for chloroplasts of different ages. Both tissue
and age selectivity are determined by the transit peptide of each preprotein, and
a transit-peptide motif for older-chloroplast preference has been identified.
Future challenges lie in identifying other motifs for tissue and age selectivity,
as well as in identifying the receptor components that decipher these motifs.
Developmental regulation also suggests that caution should be exercised when
comparing protein import data generated with plastids isolated from different
tissues or with chloroplasts isolated from plants of different ages.
PMID- 29943362
TI - Uniform Field Resonators for EPR Spectroscopy: A Review.
AB - Cavity resonators are often used for electron paramagnetic resonance (EPR).
Rectangular TE102 and cylindrical TE011 are common modes at X-band even though
the field varies cosinusoidally along the Z-axis. The authors found a way to
create a uniform field (UF) in these modes. A length of waveguide at cut-off was
introduced for the sample region, and tailored end sections were developed that
supported the microwave resonant mode. This work is reviewed here. The radio
frequency (RF) magnetic field in loop-gap resonators (LGR) at X-band is uniform
along the Z-axis of the sample, which is a benefit of LGR technology. The LGR is
a preferred structure for EPR of small samples. At Q-band and W-band, the LGR
often exhibits nonuniformity along the Z-axis. Methods to trim out this
nonuniformity, which are closely related to the methods used for UF cavity
resonators, are reviewed. In addition, two transmission lines that are new to
EPR, dielectric tube waveguide and circular ridge waveguide, were recently used
in UF cavity designs that are reviewed. A further benefit of UF resonators is
that cuvettes for aqueous samples can be optimum in cross section along the full
sample axis, which improves quantification in EPR spectroscopy of biological
samples.
PMID- 29943363
TI - Predictors of surgical outcome and early criteria of remission in acromegaly-some
controversial issues.
PMID- 29943364
TI - Aspirin for Primary Prevention of Cardiovascular Disease and Renal Disease
Progression in Chronic Kidney Disease Patients: a Multicenter Randomized Clinical
Trial (AASER Study).
AB - BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk for
developing cardiovascular events. However, limited evidence is available
regarding the use of aspirin in CKD patients to decrease cardiovascular risk and
to slow renal disease progression. STUDY DESIGN: Prospective, multicenter, open
label randomized controlled trial. SETTING AND PARTICIPANTS: One hundred eleven
patients with estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73 m2
without previous cardiovascular events. INTERVENTION: Aspirin treatment (100
mg/day) (n = 50) or usual therapy (n = 61). Mean follow-up time was 64.8 +/- 16.4
months. OUTCOMES: The primary endpoint was composed of cardiovascular death,
acute coronary syndrome (nonfatal MI, coronary revascularization, or unstable
angina pectoris), cerebrovascular disease, heart failure, or nonfatal peripheral
arterial disease. Secondary endpoints were fatal and nonfatal coronary events,
renal events (defined as doubling of serum creatinine, >= 50% decrease in eGFR,
or renal replacement therapy), and bleeding episodes. RESULTS: During follow-up,
17 and 5 participants suffered from a primary endpoint in the control and aspirin
groups, respectively. Aspirin did not significantly reduce primary composite
endpoint (HR, 0.396 (0.146-1.076), p = 0.069. Eight patients suffered from a
fatal or nonfatal coronary event in the control group compared to no patients in
the aspirin group. Aspirin significantly reduced the risk of coronary events (log
rank, 5.997; p = 0.014). Seventeen patients in the control group reached the
renal outcome in comparison with 3 patients in the aspirin group. Aspirin
treatment decreased renal disease progression in a model adjusted for age,
baseline kidney function, and diabetes mellitus (HR, 0.272; 95% CI, 0.077-0.955;
p = 0.043) but did not when adjusted for albuminuria. No differences were found
in minor bleeding episodes between groups and no major bleeding was registered.
LIMITATIONS: Small sample size and open-label trial. CONCLUSIONS: Long-term
treatment with low-dose aspirin did not reduce the composite primary endpoint;
however, there were reductions in secondary endpoints with fewer coronary events
and renal outcomes. ClinicalTrials.gov Identifier: NCT01709994.
PMID- 29943365
TI - Thrombopoietin Levels During Tyrosine Kinase Inhibitor Therapy for Chronic
Myeloid Leukemia.
AB - BACKGROUND AND OBJECTIVE: Although it is well known that platelet depletion is
one of the major adverse events related to tyrosine kinase inhibitor (TKI)
therapy, the effect of TKIs on thrombopoietin (TPO), a stimulating factor for
thrombopoiesis, has not been examined to date. In this study, we investigated the
effect of TKIs on the levels of plasma TPO concentration in patients with well
controlled chronic myeloid leukemia receiving imatinib or dasatinib and those in
treatment-free remission (TFR). METHODS: Blood samples for blood cell counts and
plasma TPO levels were obtained from 23 dasatinib-treated patients before and 1 h
after intake, 11 patients treated with imatinib before and 2 h after intake, and
nine TFR patients. Levels of plasma TPO were determined by using enzyme-linked
immunosorbent assays. RESULTS: Levels of TPO were significantly inversely
correlated with platelet counts in the entire cohort (r = - 0.568, p < 0.0001).
Dasatinib intake, but not imatinib, significantly reduced platelet counts after
intake (p = 0.0009 in dasatinib and p = 0.5431 in imatinib). However, imatinib
and dasatinib intake increased the levels of TPO in these patients (p = 0.0024,
dasatinib; p = 0.0098, imatinib). CONCLUSIONS: Our study results suggest that
neither dasatinib nor imatinib therapy inhibits TPO production. Rather, transient
increases in TPO levels seen with these two treatments might be a result of the
decrease in TPO clearance these TKIs confer. However, further investigations are
required to clarify the effect of TKIs on thrombopoiesis.
PMID- 29943366
TI - Influence of involuntary facial expressions on reproducibility of 3D
stereophotogrammetry in children with and without complete unilateral cleft lip
and palate from 3 to 18 months of age.
AB - OBJECTIVES: To assess the influence of involuntary facial expressions on 3D
facial stereophotogrammetry reproducibility in children with and without
unilateral cleft lip, alveolus and palate (UCLP) aged 3-18 months. MATERIALS AND
METHODS: Three to eight 3D facial images per time point were acquired within 10
min of 31 children with UCLP and 50 controls at 3, 12 and 18 months of age. 3D
mapping of two 3D facial images per subject per age was performed. Distance kits
of the full face and nasolabial area were calculated. RESULTS: In the total
subject pool, mean variation between two 3D facial images ranged from 0.38-0.88
mm. There were no significant differences within groups for the various ages.
Variation between controls and UCLP subjects did not differ significantly.
Variation was higher in the nasolabial area than in the full face. CONCLUSIONS:
The influence of involuntary facial expressions on the estimation of facial
growth should not be underestimated, especially in the nasolabial region of UCLP
subjects aged 3 months. To improve 3D facial imaging reliability, image capturing
should be performed by a trained photographer following a meticulous image
capturing protocol, including thorough review after capture. CLINICAL RELEVANCE:
Facial 3D stereophotogrammetry is a useful tool for monitoring facial growth
longitudinally in young children with facial deformities, as no radiation is
involved and image capture is easy and fast. It can be performed reliably in
children with and without UCLP aged 3-18 months by an experienced photographer
utilising a meticulous image capturing protocol.
PMID- 29943367
TI - Metabolomics profiling of cleidocranial dysplasia.
AB - OBJECTIVES: Cleidocranial dysplasia (CCD) is a rare autosomal-dominantly
inherited skeletal dysplasia that is predominantly associated with heterozygous
mutations of RUNX2. However, no information is available regarding metabolic
changes associated with CCD at present. MATERIALS AND METHODS: We analyzed
members of a CCD family and checked for mutations in the RUNX2 coding sequence
using the nucleotide BLAST program. The 3D protein structure of mutant RUNX2 was
predicted by I-TASSER. Finally, we analyzed metabolites extracted from plasma
using LC-MS/MS. RESULTS: We identified a novel mutation (c.1061insT) that
generates a premature termination in the RUNX2 coding region, which, based on
protein structure prediction models, likely alters the protein's function.
Interestingly, metabolomics profiling indicated that 30 metabolites belonging to
13 metabolic pathways were significantly changed in the CCD patients compared to
normal controls. CONCLUSIONS: The results highlight interesting correlations
between a RUNX2 mutation, metabolic changes, and the clinical features in a
family with CCD. The results also contribute to our understanding of the
pathogenetic processes underlying this rare disorder. CLINICAL RELEVANCE: This
study provides the first metabolomics profiling in CCD patients, expands our
insights into the pathogenesis of the disorder, may help in diagnostics and its
refinements, and may lead to novel therapeutic approaches to CCD.
PMID- 29943368
TI - Anesthetic efficacy of an inferior alveolar nerve block in soft tissue and
correlation between soft tissue and pulpal anesthesia.
AB - OBJECTIVES: This study was aimed at evaluating the anesthetic success rates in
various regions of soft tissue after inferior alveolar nerve (IAN) block and
comparing the success rates of soft tissue anesthesia with those of pulpal
anesthesia to find correlations. MATERIALS AND METHODS: Fifty-nine dental
students received an IAN block injection. A total of four test sites were used
for soft tissue anesthesia using a pressure algometer (PA): the corner of the
lower lip vermilion border (LL); the buccal-attached gingiva of the lateral
incisor (BGI), the molar (BGM), and the lingual gingiva (LG). The lateral incisor
(LI) and the first molar (M1) were evaluated for pulpal anesthesia using an
electric pulp tester. To evaluate whether soft tissue anesthesia can be an
indicator of pulpal anesthesia, the positive predictive value (PPV) and negative
predictive value (NPV) were calculated. RESULTS: The highest success rate for
soft tissue anesthesia was seen on the LG (93.9%), followed by LL (79.6%), BGI
(53.1%), and BGM (14.3%). The PPVs of LL for the M1 and Ll were 74.4 and 59.0%.
The NPVs for the M1 and LI were much higher in the LL (90.0 and 100%,
respectively) than in the BGI (56.5 and 69.6%, respectively). CONCLUSIONS: The
highest success rate was found in the LG. Lip numbness was not an indicator of
pulpal anesthesia of M1 and LI. However, if the LL was not anesthetized, the
probabilities of failed pulpal anesthesia were very high in the LI and M1.
CLINICAL RELEVANCE: The clinicians need to consider not doing an additional
lingual nerve block after IAN block.
PMID- 29943369
TI - The antimicrobial properties, cytotoxicity, and differentiation potential of
double antibiotic intracanal medicaments loaded into hydrogel system.
AB - OBJECTIVE: This study evaluated the antimicrobial properties, cytotoxicity, and
mineralization potential of methylcellulose hydrogels loaded with low
concentrations of double antibiotic pastes (DAP). MATERIALS AND METHODS: The
direct and residual antibacterial effects of 1, 5, and 10 mg/mL of DAP loaded
into hydrogels as well as calcium hydroxide (Ca(OH)2) were tested against single
species biofilms of Enterococcus faecalis and dual-species biofilms (Enterococcus
faecalis and Prevotella intermedia). The effects of DAP hydrogels on
proliferation and mineralization of dental pulp stem cells (DPSC) were tested
using MTT assays, alkaline phosphate activity (ALP), and alizarin red staining.
Fisher's exact tests, Wilcoxon rank sum tests, and one-way ANOVA were used for
statistical analyses (alpha = 0.05). RESULTS: All tested concentrations of DAP
hydrogels as well as Ca(OH)2 demonstrated significant direct antibacterial
effects against single- and dual-species biofilms. However, only 5 and 10 mg/mL
of DAP hydrogels exhibited significant residual antibacterial effects against
both types of tested biofilms. Only 1 mg/mL of DAP hydrogels did not have
significant negative effects on DPSC viability, ALP activity, and mineralization
nodule formation. However, 5 and 10 mg/mL of DAP hydrogels caused significant
negative effects on cytotoxicity and mineralization nodule formation of DPSC.
CONCLUSIONS: Hydrogels containing 1 mg/mL DAP offered significant direct
antibacterial effects against single- and dual-species biofilms without causing
significant negative effects on viability, ALP activity, and mineralization
nodule formation of DPSC. CLINICAL RELEVANCE: The methylcellulose-based hydrogel
proposed in this study can be used clinically as a biocompatible system to
deliver controlled low concentrations of DAP.
PMID- 29943370
TI - Single-center experience of the bridge-to-bridge strategy using the Nipro
paracorporeal ventricular assist device.
AB - Currently, we use the Nipro paracorporeal VAD (p-VAD) for initial short-term
ventricular support, as a bridge to decision (BTD) or a bridge to candidacy (BTC)
treatment, in Interagency Registry for Mechanically Assisted Circulatory Support
(INTERMACS) levels 1 and 2 patients. However, it is possible that compared to
patients with primary implantable-VADs (P-iVAD), the bridge-to-bridge (BTB)
patients are more likely to develop complications. This retrospective study used
data from 24 consecutive BTB patients who were initially implanted with Nipro p
VAD as BTD or BTC treatments between April 2011 and March 2016, and subsequently
underwent conversion to an i-VAD. The data from 72 patients who underwent a
primary i-VAD (P-iVAD) procedure were used for comparison. Between the two
groups, there was no significant difference in the incidence of infectious events
(p = 0.72) or stroke (p = 0.44). Orthotropic heart transplantation was performed
in 6 of the 24 patients in the BTB group and in 21 of the 72 patients in the P
iVAD group. The 1- and 2-year survival rates were 95.8% and 95.8% in the BTB
group and 91% and 85.8% in the P-iVAD group; these values were not significantly
different between groups (p = 0.91). Based on these results we conclude that BTB
using Nipro p-VAD is a reasonable strategy for treating patients with severe
decompensated end-stage heart failure.
PMID- 29943371
TI - Proteomics and bioinformatics analyses identify novel cellular roles outside
mitochondrial function for human miro GTPases.
AB - The human Miro GTPases (hMiros) have recently emerged as important mediators of
mitochondrial transport and may significantly contribute to the development of
disorders such as Alzheimer's and schizophrenia. The hMiros represent two highly
atypical members of the Ras superfamily, and exhibit several unique features: the
presence of a GTPase domain at both the N-terminus and C-terminus, the presence
of two calcium-binding EF-hand domains and localisation to the mitochondrial
outer membrane. Here, elucidation of Miro GTPase signalling pathway components
was achieved through the use of molecular biology, cell culture techniques and
proteomics. An investigation of this kind has not been performed previously; we
hoped, through these techniques, to enable the profiling and identification of
pathways regulated by the human Miro GTPases. The results indicate several novel
putative interaction partners for hMiro1 and hMiro2, including numerous proteins
previously implicated in neurodegenerative pathways and the development of
schizophrenia. Furthermore, we show that the N-terminal GTPase domain appears to
fine-tune hMiro signalling, with GTP-bound versions of this domain associated
with a diverse range of interaction partners in comparison to corresponding GDP
bound versions. Recent evidences suggest that human Miros participate in host
pathogen interactions with Vibrio Cholerae type III secretion proteins. We have
undertaken a bioinformatics investigation to identify novel pathogenic effectors
that might interact with Miros.
PMID- 29943372
TI - Fluoride in Iranian Drinking Water Resources: a Systematic Review, Meta-analysis
and Non-carcinogenic Risk Assessment.
AB - A systematic review, meta-analysis, and non-carcinogenic risk considering
fluoride content of drinking water resources of 31 provinces of Iran among some
international databases such as Science Direct, Scopus, PubMed, and national
databases including SID and Irandoc (2011 to July 2017) were conducted. In this
context, 10 articles (40 studies) with 1706 samples were included in meta
analyses and risk assessment studies. The pooled concentration of fluoride in the
cold, mild, and warm weather provinces were calculated as 0.39 mg/L (95% CI 0.32
0.48 mg/L), 0.52 (95% CI 0.43-0.61 mg/L), and 0.75 (95% CI 0.56-0.94 mg/L),
respectively. The pooled concentration of fluoride in Iranian drinking water
resources was 0.51 (95% CI 0.45-0.57 mg/L). The minimum and maximum
concentrations of fluoride content were related to Kermanshah (0.19 mg/L) and
Kerman (1.13 mg/L) provinces, respectively. The HQ of fluoride in the children
and adults were 0.462 and 0.077, respectively as children are more vulnerable
than adults. The HQ for children and adults was lower than 1 value. Therefore,
there is no considerable non-carcinogenic risk for consumers due to drinking
water in Iran. Although the non-carcinogenic of fluoride in drinking water was
not significant, fluoride entry from other sources, such as food or inhalation,
could endanger the health of the residents of Kerman and Bushehr provinces.
PMID- 29943374
TI - Anlotinib: First Global Approval.
AB - Jiangsu Chia-Tai Tianqing Pharmaceutical and Advenchen Laboratories are co
developing anlotinib (Focus V(r)) for the treatment of advanced cancer. Anlotinib
is an oral small molecule inhibitor of multiple receptor tyrosine kinases, with a
broad spectrum of inhibitory effects on tumour angiogenesis and growth. Anlotinib
is approved in China for the treatment of patients with locally advanced or
metastatic non-small cell lung cancer (NSCLC) who have undergone progression or
recurrence after >= 2 lines of systemic chemotherapy. Anlotinib is also
undergoing phase II and/or III clinical development for various sarcomas and
carcinomas in China, USA and Italy. This article summarizes the milestones in the
development of anlotinib leading to this first approval for NSCLC.
PMID- 29943373
TI - Postural Orthostatic Tachycardia Syndrome: Prevalence, Pathophysiology, and
Management.
AB - Postural orthostatic tachycardia syndrome (POTS) is a debilitating disease that
predominantly affects young women. It is a multifactorial disorder that is
characterized by severe tachycardia and orthostatic intolerance. Patients with
POTS experience a variety of cardiac, neurological, and immunological symptoms
that significantly reduce quality of life. In this review, a comprehensive
framework is provided to aid in helping identify and treat patients with POTS.
Given its heterogenous nature, it is crucial to understand each component of POTS
in relation to one another instead of distinct parts. The framework highlights
the overlap among the five main subtypes of POTS based on its pathophysiology
(neuropathic, hypovolemic, primary hyperadrenergic, joint-hypermobility-related,
and immune-related). Emphasis is placed on incorporating a multidisciplinary
approach when treating patients with POTS, especially with a new focus towards
immunotherapy. Although research has advanced our knowledge of POTS, there is
still a critically unmet need to further our understanding and provide patients
with the relief they need.
PMID- 29943375
TI - Regorafenib: A Review in Metastatic Colorectal Cancer.
AB - Regorafenib (Stivarga(r)) is an oral small-molecule multiple kinase inhibitor. It
is indicated worldwide for patients with metastatic colorectal cancer (mCRC). In
the EU and USA it is indicated for patients with mCRC who have been previously
treated with, or are not considered candidates for available therapies, including
fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and, if RAS wild-type,
an anti-EGFR therapy. In Japan, it is indicated for the treatment of
unresectable, advanced/recurrent CRC. The addition of regorafenib to best
supportive care prolonged median overall survival (OS; by up to 2.5 months) and
progression-free survival (PFS; by up to 1.5 months) relative to the addition of
placebo in double-blind phase 3 studies (CORRECT and CONCUR) in patients with
mCRC who had progressed after failure of standard therapy. Health-related quality
of life was not adversely affected with regorafenib relative to placebo. A large
open-label phase 3 study (CONSIGN) and several large real-world studies supported
the efficacy of regorafenib in this setting. Regorafenib had a generally
manageable tolerability profile, which was consistent with the profile of a
typical small-molecule multiple kinase inhibitor. Treatment-related adverse
events (AEs), mostly of mild or moderate severity, were reported in the majority
of patients receiving regorafenib, with dermatological toxicities and liver
enzyme elevations among the most common AEs. Although identification of
biomarkers/parameters predicting efficacy outcomes with regorafenib will help to
individualize therapy, current evidence indicates that regorafenib is a valuable
treatment option for patients with refractory mCRC who have a very poor
prognosis.
PMID- 29943377
TI - Development of Conversion Functions Mapping the FACT-B Total Score to the EQ-5D
5L Utility Value by Three Linking Methods and Comparison with the Ordinary Least
Square Method.
AB - INTRODUCTION: Health-related quality-of-life (HRQoL) measures are commonly mapped
to a value that represents a utility for economic evaluation via regression
models, which may lead to shrinkage of the variance. OBJECTIVES: This study aimed
to develop and compare conversion functions that map the Functional Assessment of
Cancer Therapy-Breast (FACT-B) total score to the EuroQoL 5-Dimensions, 5-Levels
(EQ-5D-5L) utility value via four methods. METHODS: We used the HRQoL scores of
238 Singapore patients with breast cancer to develop the conversion function for
the equipercentile, linear equating, mean rank and ordinary least squares (OLS)
methods. We compared the distributions of the observed values and the four sets
of mapped values and performed regression analyses to assess whether the
association with risk factors was preserved by utility values derived from
mapping. RESULTS: At baseline, the observed EQ-5D-5L utility value had a mean +/-
standard deviation (SD) of 0.820 +/- 0.152, and 24.8% of the respondents attained
a value of 1. The OLS method (mean 0.820; SD 0.112; proportion 0%) better agreed
with the observed data than the equipercentile (mean 0.831; SD 0.152; proportion
23.5%), linear equating (mean 0.814; SD 0.145; proportion 11.8%) and mean rank
method (mean 0.821; SD 0.147; proportion 23.9%). The significance of association
was preserved for all parameters involved in the regression analyses by the
equipercentile and linear equating methods, but the mean rank and OLS methods
were inconsistent with the observed data for one and two parameters,
respectively. CONCLUSION: The problem of shrinkage in the variance occurred in
the OLS method, but it provided an unbiased estimate for the mean and better
agreement. Among the other three linking methods, the mean rank method better
described the distribution, whereas the equipercentile and linear equating
methods better assessed the association with risk factors.
PMID- 29943376
TI - The Significance of the Intestinal Microbiome for Vaccinology: From Correlations
to Therapeutic Applications.
AB - Despite unprecedented advances in understanding the intestinal microbiome, its
potential to improve fields such as vaccinology has yet to be realized. This
review briefly outlines the immunologic potential of the intestinal microbiome
for vaccinology and highlights areas where the microbiome holds specific promise
in vaccinology. Oral rotavirus vaccine effectiveness in low-income countries is
used as a case study to describe how the intestinal microbiome may be employed to
improve a vaccine's immunogenicity. A top-down, evidence-based approach is
proposed to identify effective microbiota-based applications for vaccine
improvement. Applying evidence from field studies in pertinent populations that
correlate microbiome composition with vaccine effectiveness to appropriate
experimental platforms will lead to the identification of safe, vaccine
supporting microbiota targets that are relevant to populations in need of
improvement in vaccine-induced immunity.
PMID- 29943378
TI - Beneficial Changes in Capsicum frutescens Due to Priming by Plant Probiotic
Burkholderia spp.
AB - Plant probiotic mechanisms of endophytic microorganisms are highly remarkable as
it play key role in growth and health of plants. Even though Burkholderia spp.
have been studied for their role in plant growth and disease management, report
on their field performance is very limited. Hence, the objective of the study was
to investigate the plant probiotic performance of selected Burkholderia spp. on
Capsicum frutescens. The results of the study showed bacterial influence on
growth of C. frutescens with remarkable induction of early flowering and
fruiting. Most interestingly, the plants treated with Burkholderia strains, ZoB74
and ZoB82 were found to have limited infestation with Bemisia tabaci. However,
the control plants and those treated with Burkholderia ZoB86 were observed to
have stunted growth with crumpled and curled leaves with no flowers or fruits.
Hence, the study confirmed the strain specific potential of Burkholderia spp. in
triggering the early flowering and fruiting in C. frutescens with associated
protection from insect attack.
PMID- 29943379
TI - An integrative framework for salamander and mouse limb regeneration.
AB - Appendage regeneration is not a simple task. The animal must harness all of its
energy and resources to orchestrate perhaps one of the most complicated events
since its development. Balancing the immune response, wound healing,
proliferation, patterning and differentiation is an elegant job, and how some
animals achieve that still leaves researchers enchanted today. In this work, we
review some of the molecular aspects of regeneration, with a focus on the
axolotl, the champion of tetrapod limb regeneration, and the mouse, an excellent
mammalian model for digit tip regeneration. Advances in molecular and genomic
tools have enabled the discovery of exciting fundamental features of limb
regeneration. Integrating the data from different animal systems will be crucial
to understanding the common requirements of successful appendage regeneration and
places for flexibility. The combination of these efforts is paving the way to
grasping how good regenerators respond to the loss of body parts, how these
mechanisms might compare in modest regenerators, and, ultimately, in developing
approaches for improving regenerative outcomes in humans.
PMID- 29943381
TI - Erratum.
PMID- 29943380
TI - Editorial: Distinguishing between the challenges posed by surface and deep forms
of heterogeneity to diagnostic systems: do we need a new approach to subtyping of
child and adolescent psychiatric disorders.
AB - Diagnostic formulations attempt to impose order on the messy reality of
psychopathological phenomena. By doing this, so their advocates argue, they
provide both the platform necessary for systematic scientific study, and,
crucially, the bridge of shared terms and concepts vital if psychiatric science
is to be truly translational; where scientific endeavour is guided by clinical
priorities and, in-turn, scientific findings innovate clinical practice. The
diagnostic schemes we currently work with, taking DSM-5 as the obvious case, are
the product of an interesting historical process of ongoing revision - at the
same time pragmatic and scientific. On the one hand, it is a process both
anchored firmly in historical precedent and constrained by the practical needs of
clinicians, patients and health insurance companies. On the other hand, it is a
process open to new empirical data about how to best cluster symptomatic
expressions and differentiate clinical presentations - so that over historical
time diagnostic categories achieve an increasingly accurate mapping of the
taxonomy (i.e., underlying structure), and related pathophysiology, of
psychiatric phenomenon. Resolving the inevitable tensions that arise when trying
to reconcile these pragmatic (economic and professional) and scientific
priorities has proved to be both challenging and contentious. The study of
heterogeneity as exemplified by the articles highlighted in this editorial
indicate a range of different approaches that can be effectively used to refine
psychiatric taxonomies by incorporating developmental and pathophysiological data
to help identify new putative subtypes of potential therapeutic significance.
PMID- 29943382
TI - Quantifying the regression to the mean effect in Poisson processes.
AB - Regression to the mean (RTM) can occur whenever an extreme observation is
selected from a population and a later observation is closer to the population
mean. A consequence of this phenomenon is that natural variability can be
mistaken as real change. Simple expressions are available to quantify RTM when
the underlying distribution is bivariate normal. However, there are many real
world situations, which are better approximated as a Poisson process. Examples
include the number of hard disk failures during a year, the number of cargo ships
damaged by waves, daily homicide counts in California, and the number of deaths
per quarter attributable to acquired immune deficiency syndrome in Australia. In
this paper, we derive expressions for quantifying RTM effects for the bivariate
Poisson distribution for both the homogeneous and inhomogeneous cases.
Statistical properties of our derivations have been evaluated through a
simulation study. The asymptotic distributions of RTM estimators have been
derived. The RTM effect for the number of people killed in road accidents in
different regions of New South Wales (Australia) is estimated using maximum
likelihood.
PMID- 29943383
TI - Urine flow rate curve shapes and their descriptors.
AB - AIMS: To review the descriptors and definitions of urine flow rate curve shape
with a view to promoting greater clarity and to propose standard terms METHODS: A
search was made in the PubMed and ICS standardization documents on urine flow
rate curve shape. RESULTS: The flow shape descriptors and their definitions are
summarized and presented. "Normal" was widely used for describing a bell-shaped
flow curve, and "plateau" was mostly used where the ICS describe "constrictive"
flow shape. The use of shape descriptors "fluctuating," "compressive," "tower
shaped," and "intermittent" varied in the literature. CONCLUSION: This survey
provides an overview of flow shape descriptors and their definitions. We suggest
it is clearer to use only descriptors that describe shape alone, that is, normal,
fluctuating, intermittent, and plateau, with comments on symmetry and Qmax .
PMID- 29943384
TI - The efficacy of vaginal suppository based on myrtle in patients with
cervicovaginal human papillomavirus infection: A randomized, double-blind,
placebo trial.
AB - Human papillomavirus (HPV) can be detected in most of cervical cancers. Due to
antiviral, antimutagenic, and proapoptotic activities of myrtle, this study was
designed to investigate the effect of a herbal suppository based on myrtle in
cervicovaginal HPV infections. This study was performed as a double-blind
randomized trial at the Clinic of Traditional Medicine in Mashhad University of
Medical Sciences between 2016 and 2017. Sixty women, 18 to 50 years old, with
cervicovaginal HPV infection, were included and randomly allocated to two groups.
Sixty placebo or herbal vaginal suppositories were prescribed for 3 months (20
suppositories at each menstrual cycle). Each herbal vaginal suppository contained
10% of myrtle aqueous extract and 0.5% of myrtle essential oil. The HPV test and
colposcopic findings were evaluated after treatment. There was no difference
between two groups as regards lesion site, diagnosis time of disease, and HPV
type before intervention (p >= 0.05). At the end of the study, the HPV test was
negative in 92.6% and 62.6% of the intervention and placebo groups, respectively
(p = 0.036). The change in cervical lesion size was 71.4% and 30.4% in the
intervention and placebo groups, respectively, based on colposcopic findings (p =
0.015). It seems that herbal suppository can speed up virus clearance and can be
effective in treating HPV infection.
PMID- 29943385
TI - Endoscopic papillary large balloon dilation and endoscopic papillary balloon
dilation both without sphincterotomy for removal of large bile duct stones: A
propensity-matched analysis.
AB - BACKGROUND AND AIM: Endoscopic papillary large balloon dilation (EPLBD) without
endoscopic sphincterotomy (EST) may facilitate extraction of large bile duct
stones through achieving adequate dilation of the ampulla. However, contrary to
favorable long-term outcomes after endoscopic papillary balloon dilation (EPBD),
that of EPLBD without EST has been little investigated. Therefore, we conducted
the current study to evaluate short- and long-term outcomes of EPLBD without EST
and EPBD after removal of large bile duct stones (LBDS; >=10 mm). METHODS: This
retrospective study included patients without a previous history of EST, EPBD or
EPLBD who underwent EPLBD without EST or EPBD for removal of LBDS. Each patient
in the EPLBD without EST group was matched to a patient in the EPBD group using
propensity scores. RESULTS: Forty-four patients in each group were matched for
the analysis. Baseline characteristics were balanced after propensity matching.
Rate of complete stone removal in a single session was higher (80% vs 16%, P <
0.001), number of ERCP sessions (1.3 +/- 0.7 vs 2.4 +/- 1.5, P < 0.001) and rate
of lithotripsy use (30% vs 80%, P < 0.001) were smaller in the matched EPLBD
without EST group. Contrary to null between-group differences in early adverse
events (P = 0.99), a cumulative rate of late biliary complications was higher in
the EPLBD without EST group (P = 0.02). CONCLUSION: EPLBD without EST showed
higher efficacy for removal of LBDS but was associated with worse long-term
outcomes when compared to EPBD.
PMID- 29943386
TI - Bone regeneration by freeze-dried composite of octacalcium phosphate collagen and
teriparatide.
AB - OBJECTIVE: Octacalcium phosphate (OCP) and collagen (col) composite (OCPcol)
demonstrated superior bone regeneration properties, and its commercialization
appears to be forthcoming. As a practical medical material for new combination
products, we developed a freeze-dried composite with OCPcol and teriparatide
(TPTD) (OCPcolTPTDf), and investigated its bone regenerative properties.
MATERIALS AND METHODS: A disk of OCPcol was made by mixing OCP granules and
atelocollagen for medical use. Then, OCPcolTPTDf was prepared by impregnation of
the OCPcol disk with 1.0 or 0.1 ug of TPTD solution (OCPcolTPTDf 1.0 and
OCPcolTPTDf 0.1, respectively) followed by lyophilization. In vitro release
profiles of TPTD from OCPcolTPTDf were determined using an enzyme-linked
immunosorbent assay. Implantation of OCPcolTPTDf or OCPcol was carried out for a
rat critical-sized calvarial defect. And five defects in each group were
collected after 12 weeks of implantation. RESULTS: The retention-release profiles
of TPTD from OCPcolTPTDf supported a higher degree of retention of TPTD.
Radiographic, histological, and histomorphometric examinations indicated that
regenerated bone was filled in most of the defects of the OCPcolTPTDf.
Additionally, the OCPcolTPTDf groups showed significantly enhanced bone
regeneration compared with the OCPcol group. CONCLUSIONS: These results suggested
that this newly developed bone regenerative composite could be a practical
medical material.
PMID- 29943387
TI - Plasma levels of free fatty acids correlate with type 2 diabetes mellitus.
AB - AIMS: Free fatty acids (FFA) mediate adverse metabolic effects such as
downregulated carbohydrate metabolisms, providing causal links between obesity
and the development of type 2 diabetes mellitus (T2DM). Here, we investigated the
plasma concentrations of FFA alone and in combination with protein glycation as
potential diagnostic and prognostic biomarkers of T2DM. MATERIALS AND METHODS:
EDTA-plasma obtained from 48 newly diagnosed male T2DM patients, 48 long-term
controlled (24 male and 24 female) T2DM patients, 20 prediabetic male T2DM
patients and two age-matched control cohorts (48 non-diabetic (ND) men; 24 male
and 24 female ND partipants) were analysed for a set of clinical parameters
including FFA. Glycation sites were quantified after tryptic digestion using
tandem mass spectrometry. RESULTS: Median plasma concentrations of FFA were
almost three-fold higher in samples obtained from newly diagnosed (long-term
controlled) T2DM patients than in those obtained from the control group,
providing diagnostic sensitivity (SN) of 92% (85%) and specificity (SP) of 90%
(88%). When combined with the glycation level of lysine-141 of haptoglobin,
diagnostic accuracy improved further for newly diagnosed (SN, 94%; SP 96%) and
long-term controlled (SN, 85%; SP, 94%) T2DM patients (HbA1c: SN, 88%; SP, 96%).
A prospective pilot study evaluating the prognostic value revealed initially low
FFA levels for pre-diabetic patients that increased in the following four years
in patients whose prediabetic state worsened or who developed T2DM. CONCLUSIONS:
FFA levels are elevated in newly diagnosed and long-term controlled T2DM
patients, providing high diagnostic accuracy of 87% and 91%, respectively, which
improved further when combined with the glycation degree of lysine-141 in
haptoglobin. Additionally, FFA showed higher mean fold-changes than HbA1c or FPG
in subjects developing T2DM, indicating higher sensitivity towards the
progression of the disease.
PMID- 29943388
TI - Solvothermally Controlled Synthesis of Organic-Inorganic Hybrid Nanosheets as
Efficient pH-Universal Hydrogen-Evolution Electrocatalysts.
AB - Electrocatalysts with a high efficiency and durability for the hydrogen evolution
reaction (HER) hold tremendous promise for next-generation energy conversion.
Among the state-of-art catalysts for HER, organic-inorganic hybrid nanosheets
exhibit a great potential with the merits of high activity, good durability, and
low cost. Nevertheless, there is no general method for the synthesis of binary
metal phosphide hybrid nanosheet HER catalysts with a tunable morphology and
composition. Herein, we report a facile approach for the synthesis of nanosheets
consisting of a binary cobalt nickel phosphide hybrid with a hierarchically
porous nanostructures using an oxidation- phosphorization process. The as
optimized hybrid nanosheets annealed at 350 degrees C yield the highest pH
universal activity with overpotentials of 148, 111, and 173 mV in acidic,
alkaline, and neutral media, respectively. Besides the promoted mass diffusion in
the hierarchically porous structure, the extraordinary performance can be also
attributed to the weakened adsorption of hydrogen as a result of the tunable
composition of Co and Ni, which was revealed by first-principles calculations.
PMID- 29943389
TI - NK4 inhibits the proliferation and induces apoptosis of human rheumatoid
arthritis synovial cells.
AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
proliferation and insufficient apoptosis of synovial cells. NK4 is a hepatocyte
growth factor antagonist and is implicated in cell proliferation, viability, and
apoptosis of many tumour cells. This study aimed to investigate the role of NK4
in the regulation of human RA synovial cell proliferation and apoptosis.
Fibroblast-like synoviocytes (FLSs) isolated from RA patients and MH7A synovial
cells were subjected to MTT, flow cytometry, and Western blot analysis. We found
that NK4 suppressed cell proliferation through cell cycle arrest at the G0/G1
phase and induced apoptosis in RA synovial cells. Furthermore, NK4 altered the
expression of cell cycle and apoptosis-related proteins such as cyclin D1, cyclin
B1, PCNA, p21, p53, Bcl-2, Bax, cleaved caspase-9, and cleaved caspase-3.
Additionally, NK4 reduced the phosphorylation level of NF-kappaB p65 and
upregulated the expression of sirt1, but did not change the levels of p38 and p
p38 in RA-FLS and MH7A cells. In conclusion, NK4 inhibits the proliferation and
induces apoptosis of human RA synovial cells. NK4 is a promising therapeutic
target for RA. We demonstrated that NK4 inhibited cell proliferation by inducing
apoptosis and arresting cell cycle in RA-FLS and MH7A cells. The apoptotic
effects of NK4 may be mediated in part by decreasing Bcl-2 protein level,
increasing Bax and caspase 3 protein levels, and inhibiting NF-kappaB signalling
in RA-FLS and MH7A cells. These findings reveal potential mechanism underlying
the role of NK4 in RA synovial cells and suggest that NK4 is a promising agent
for RA treatment.
PMID- 29943390
TI - Refining nursing assessment and management with a new postanaesthetic care
discharge tool to minimize surgical patient risk.
AB - AIMS: To evaluate use of an evidence-based discharge tool, the Post-Anaesthetic
Care Tool and its impact on nursing assessment, communication, and management of
patients in the postanaesthetic care unit. BACKGROUND: Postanaesthetic care unit
nurses manage patients immediately after surgery and make clinical decisions on
discharge readiness. There is a lack of evidence-based guidance on assessing,
documenting, and communicating the patient's postoperative experience. The Post
Anaesthetic Care Tool, which includes instructions for assessing discharge
readiness and incorporates the ISOBAR acronym, was developed following a
comprehensive systematic review and expert consultation. DESIGN AND METHODS: This
quasiexperimental, multicentre, nonrandomized study was conducted in three
postanaesthetic care units in Australia. Participants were nurses providing care
to adults postgeneral anaesthesia. Episodes of care were observed before (N =
723) and after (N = 694) introduction of the evidence-based tool. Statistical
methods (Chi-Square and Mann-Whitney U-Tests) were undertaken to analyse nursing
assessment, communication, and management outcomes before and after
implementation of the Post-Anaesthetic Care Tool. RESULTS: The Post-Anaesthetic
Care Tool was associated with statistically significant improvements in the
frequency of nursing assessment and responsiveness to complications including
pain, nausea/vomiting and hypothermia. After the tool's introduction, nurses
requested more medical reviews. This was associated with increased recognition of
clinical deterioration and significant improvements in clarity of handover from
the postanaesthetic care unit to the ward. CONCLUSIONS: The structured discharge
tool, Post-Anaesthetic Care Tool, was associated with improved nursing management
of patients in the postanaesthetic care unit and enabled early identification and
response to clinical concerns.
PMID- 29943391
TI - Serotonin, behavior, and natural selection in New World monkeys.
AB - Traits that undergo massive natural selection pressure, with multiple events of
positive selection, are hard to find. Social behaviour, in social animals, is
crucial for survival, and genetic networks involved in behaviour, such as those
of serotonin (5-HT) and other neurotransmitters, must be the target of natural
selection. Here, we used molecular analyses to search for signals of positive
selection in the 5-HT system and found such signals in the M3-M4 intracellular
domain of the 5-HT3A serotonin receptor subunit (HTR3A) in primates. We detected
four amino acid sites with signs of putatively positive selection (398, 403, 432
and 416); the first three showed indications of being selected in New World
monkeys (NWM, Platyrrhini), specifically in the Callitrichinae branch.
Additionally, we searched for associations of these amino acid variants with
social behavioural traits (i.e. sex-biased dispersal, dominance and social
monogamy) using classical and Bayesian methods, and found statistically
significant associations for unbiased sex dispersal (398L and 416S), unbiased sex
dominance (416S) and social monogamy (416S), as well as significant positive
correlation between female dispersal and 403G. Furthermore, we found putatively
functional protein motifs determined by three selected sites, of which we
highlight a ligand motif to GSK3 in the 416S variant, appearing only in
Platyrrhini. 5-HT, 5-HT3A receptor and GSK3 are part of a network that
participates in neurodevelopment and regulates behaviour, among other functions.
We suggest that these genetic variations, together with those found in other
neurotransmitter systems, must contribute to adaptive behaviours and consequently
to fitness in NWMs.
PMID- 29943392
TI - A Solid-State Fibriform Supercapacitor Boosted by Host-Guest Hybridization
between the Carbon Nanotube Scaffold and MXene Nanosheets.
AB - Fiber-shaped supercapacitors with improved specific capacitance and high rate
capability are a promising candidate as power supply for smart textiles. However,
the synergistic interaction between conductive filaments and active nanomaterials
remains a crucial challenge, especially when hydrothermal or electrochemical
deposition is used to produce a core (fiber)-shell (active materials) fibrous
structure. On the other hand, although 2D pseudocapacitive materials, e.g., Ti3
C2 T x (MXene), have demonstrated high volumetric capacitance, high electrical
conductivity, and hydrophilic characteristics, MXene-based electrodes normally
suffer from poor rate capability owing to the sheet restacking especially when
the loading level is high and solid-state gel is used as electrolyte. Herein, by
hosting MXene nanosheets (Ti3 C2 T x ) in the corridor of a scrolled carbon
nanotube (CNT) scaffold, a MXene/CNT fiber with helical structure is successfully
fabricated. These features offer open spaces for rapid ion diffusion and
guarantee fast electron transport. The solid-state supercapacitor based on such
hybrid fibers with gel electrolyte coating exhibits a volumetric capacitance of
22.7 F cm-3 at 0.1 A cm-3 with capacitance retention of 84% at current density of
1.0 A cm-3 (19.1 F cm-3 ), improved volumetric energy density of 2.55 mWh cm-3 at
the power density of 45.9 mW cm-3 , and excellent mechanical robustness.
PMID- 29943393
TI - Flavonoids of Artocarpus heterophyllus Lam. heartwood inhibit the innate immune
responses of human phagocytes.
AB - OBJECTIVES: To investigate the effects of flavonoids isolated from Artocarpus
heterophyllus. heartwood on chemotaxis, phagocytosis, reactive oxygen species
(ROS) production and myeloperoxidase (MPO) activity of human phagocytes. METHODS:
Chemotaxis was evaluated using a modified Boyden chamber and phagocytosis was
determined by flowcytometer. Respiratory burst was investigated by luminol-based
chemiluminescence assay while MPO activity was determined by colorimetric assay.
KEY FINDINGS: Artocarpanone and artocarpin strongly inhibited all steps of
phagocytosis. Artocarpanone and artocarpin showed strong chemotactic activity
with IC50 values of 6.96 and 6.10 MUm, respectively, which were lower than that
of ibuprofen (7.37 MUm). Artocarpanone was the most potent compound in inhibiting
ROS production of polymorphonuclear leucocytes and monocytes with IC50 values
comparable to those of aspirin. Artocarpin at 100 MUg/ml inhibited phagocytosis
of opsonized bacteria (28.3%). It also strongly inhibited MPO release with an
IC50 value (23.3 MUm) lower than that of indomethacin (69 MUm). Structure
activity analysis indicated that the number of hydroxyl group, the presence of
prenyl group and variation of C-2 and C-3 bonds might contribute towards their
phagocytosis. CONCLUSIONS: Artocarpanone and artocarpin were able to suppress
strongly the phagocytosis of human phagocytes at different steps and have
potential to be developed into potent anti-inflammatory agents.
PMID- 29943394
TI - Endocrine mucin-producing sweat gland carcinoma: A study of 11 cases with
molecular analysis.
AB - BACKGROUND: Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare,
low-grade adnexal neoplasm that most commonly involves the eyelid. Analogous to
solid papillary carcinoma of the breast, it probably represents a precursor
lesion to mucinous carcinoma. Here, we describe 11 cases of EMPSGC with molecular
analysis. METHODS: We performed a retrospective search of the Johns Hopkins
Medical Institute pathology database and identified 11 cases of EMPSGC.
Immunohistochemistry was performed for chromogranin, synaptophysin, neuron
specific enolase, estrogen receptor (ER), epithelial membrane antigen (EMA),
cytokeratin 7 (CK7), and cytokeratin 20 (CK20). Array comparative genomic
hybridization (aCGH) and BRAFV600E pyrosequencing were performed on two and three
cases, respectively. RESULTS: We observed a strong female predilection (73%
females, 8/11 cases) with an average age of 66 years (range, 56-83 years).
EMPSGCs were associated with adjacent benign sweat gland cysts (3/11), atypical
intraductal proliferation (1/11), and mucinous carcinoma (1/11).
Immunohistochemically, all tumors expressed at least one neuroendocrine marker,
ER, EMA, and CK7, and were negative for CK20. aCGH demonstrated a 6p11.2 to
6q16.1 deletion (1/2 cases). All cases were negative for BRAFV600E mutation (3/3
cases). CONCLUSION: This series provides further histopathologic support that
EMPSGC represents a multistage progression to mucinous carcinoma. Additional
studies are needed to understand its molecular mechanisms.
PMID- 29943395
TI - Effects of tumour necrosis factor-alpha and interleukin-1 beta on in vitro
development of bovine secondary follicles.
AB - The objective of this study was to determine the effects of TNF-alpha and IL
1beta on development and survival of bovine secondary follicle culture in vitro
for 18 days. Secondary follicles (~0.2 mm) were isolated from ovarian cortex and
individually cultured at 38.5 degrees C, with 5% CO2 in air, for 18 days, in TCM
199+ alone (cultured control) or supplemented with 10 ng/ml IL-1beta, 10 ng/ml
TNF-alpha or both TNF-alpha and IL-1beta. The effects of these treatments on
growth, follicular survival, antrum formation, viability, ultrastructure and mRNA
levels for GDF-9, c-MOS, H1foo and Cyclin B1 were evaluated. The results showed
that addition of TNF-alpha to culture medium increased follicular diameter and
rate of antrum formation, whereas that of IL-1beta and a mixture of IL-1beta and
TNF-alpha did not do so. Ultrastructural analysis showed that, among the tested
cytokine treatments, follicles cultured in the presence of TNF-alpha had the best
preserved oocytes and granulosa cells. The presence of TNF-alpha, IL-1beta or
both did not influence the expression of mRNAs analysed. In conclusion, in
contrast to IL-1beta, TNF-alpha promotes growth of and antrum formation in in
vitro cultured bovine secondary follicles, while their ultrastructure and
viability were maintained.
PMID- 29943396
TI - Investigation of potent odorants generated during the production of whey protein
hydrolysates.
AB - Whey protein hydrolysates (WPH) were prepared from whey protein concentrate (WPC)
by partial or extensive hydrolysis. WPC and two WPH types were characterized by a
descriptive sensory analysis. WPC exhibited a "milky", "sweet", and "mild milk
fat" odor, whereas extensively hydrolyzed whey protein (E-WPH) demonstrated
"cheese-like", "acrid odor", and "sour" olfactory characteristics. In E-WPH, 3
(methylthio)-propanal, phenylacetaldehyde, and 3-methylbutanoic acid were
specifically detected with high flavor dilution factors upon aroma extract
dilution analysis. These odor-active compounds likely contributed to the
olfactory characteristics of E-WPH, and their concentration increased together
with that of their respective putative precursors: free methionine,
phenylalanine, and leucine.
PMID- 29943397
TI - Chronic hand eczema: A prospective analysis of the Swiss CARPE registry focusing
on factors associated with clinical and quality of life improvement.
AB - BACKGROUND: Hand eczema (HE) is common and may follow a chronic disease course.
So far, prospective studies investigating the risk factors for disease
progression as a prerequisite for targeted prevention are scarce. OBJECTIVE: To
evaluate the overall association of HE-associated factors with clinical and
quality of life (QoL) improvement during a follow-up of 2 years. METHODS: Data of
the prospective patient cohort (N = 199) followed by the Swiss chronic HE (CHE)
registry on long-term patient management (CARPE-CH) were analysed by means of
both classic regression and semantic map analyses. RESULTS: Both severity of HE
and QoL significantly improved over the period of 2 years (P < .001). However,
20% of patients had moderate to severe HE after 2 years of follow-up. As factors
associated with an unfavourable CHE clinical course and QoL, environmental
exposures, male sex, occupational skin disease, job loss or change at baseline,
allergic contact dermatitis, a chronic disease course, palmar localization and
widespread eczema were identified. CONCLUSIONS: Analysis of prospective data from
CARPE-CH shows a complex pattern of associations among variables as shown by
semantic map and classic statistical analyses. Factors related to occupational
exposure had the highest impact on CHE.
PMID- 29943398
TI - The biotechnological potential of marine bacteria in the novel lineage of
Pseudomonas pertucinogena.
AB - Marine habitats represent a prolific source for molecules of biotechnological
interest. In particular, marine bacteria have attracted attention and were
successfully exploited for industrial applications. Recently, a group of
Pseudomonas species isolated from extreme habitats or living in association with
algae or sponges were clustered in the newly established Pseudomonas
pertucinogena lineage. Remarkably for the predominantly terrestrial genus
Pseudomonas, more than half (9) of currently 16 species within this lineage were
isolated from marine or saline habitats. Unlike other Pseudomonas species, they
seem to have in common a highly specialized metabolism. Furthermore, the marine
members apparently possess the capacity to produce biomolecules of
biotechnological interest (e.g. dehalogenases, polyester hydrolases,
transaminases). Here, we summarize the knowledge regarding the enzymatic
endowment of the marine Pseudomonas pertucinogena bacteria and report on a
genomic analysis focusing on the presence of genes encoding esterases,
dehalogenases, transaminases and secondary metabolites including carbon storage
compounds.
PMID- 29943400
TI - Perceived Marital Support and Incident Mental Illness: Evidence from the National
Comorbidity Survey.
AB - Social support in marriage may be associated with reduced risk for mental
illness. Past studies are limited by short follow up and a focus on depression. A
two-wave nationally representative survey in the United States (n = 2,503) is
used to examine whether social support in marriage is associated with the onset
of each of four clusters of disorders-internalizing, externalizing, phobic, and
bipolar-10 years later. Results indicate that higher levels of perceived marital
support were protective against internalizing, fear, and bipolar disorders, and
against incident externalizing disorders for women. Protective effects of social
support in marriage against mental illness are long-lasting, and sometimes differ
by gender. Findings suggest the importance of mental health assessment in
clinical practice.
PMID- 29943399
TI - Academic outcomes of flipped classroom learning: a meta-analysis.
AB - CONTEXT: The flipped classroom (FC), reversing lecture and homework elements of a
course, is popular in medical education. The FC uses technology-enhanced pre
class learning to transmit knowledge, incorporating in-class interaction to
enhance higher cognitive learning. However, the FC model is expensive and
research on its effectiveness remains inconclusive. The aim of this study was to
compare the efficacy of the FC model over traditional lecture-based (LB) learning
by meta-analysis. METHODS: We systematically searched MEDLINE, PubMed, ERIC,
CINAHL, EMBASE, reference lists and Association for Medical Education in Europe
(AMEE) conference books. Controlled trials comparing academic outcomes between
the FC and LB approaches in higher education were considered eligible. The main
findings were pooled using a random-effects model when appropriate. RESULTS:
Forty-six studies (9026 participants) were included, comprising four randomised
controlled trials (RCTs), 19 quasi-experimental studies and 23 cohort studies.
Study populations were health science (n = 32) and non health science (n = 14)
students. The risk of bias was high (36/37 articles). Meta-analyses revealed that
the FC had significantly better outcomes than the LB method in examination scores
(post-intervention and pre-post change) and course grades, but not in objective
structured clinical examination scores. Subgroup analyses showed the advantage of
the FC was not observed in RCTs, non-USA countries, nursing and other health
science disciplines and earlier publication years (2013 and 2014). Cumulative
analysis and meta-regression suggested a tendency for progressively better
outcomes by year. Outcome assessments rarely focused on behaviour change.
CONCLUSIONS: The FC method is associated with greater academic achievement than
the LB approach for higher-level learning outcomes, which has become more obvious
in recent years. However, results should be interpreted with caution because of
the high methodological diversity, statistical heterogeneity and risk of bias in
the studies used. Future studies should have high methodological rigour, a
standardised FC format and utilise assessment tools evaluating higher cognitive
learning and behaviour change to further examine differences between FC and LB
learning.
PMID- 29943401
TI - Development and initial testing of the self-care of chronic illness inventory.
AB - AIM: The aim was to develop and psychometrically test the self-care of chronic
illness Inventory, a generic measure of self-care. BACKGROUND: Existing measures
of self-care are disease-specific or behaviour-specific; no generic measure of
self-care exists. DESIGN: Cross-sectional survey. METHODS: We developed a 20-item
self-report instrument based on the Middle Range Theory of Self-Care of Chronic
Illness, with three separate scales measuring Self-Care Maintenance, Self-Care
Monitoring, and Self-Care Management. Each of the three scales is scored
separately and standardized 0-100 with higher scores indicating better self-care.
After demonstrating content validity, psychometric testing was conducted in a
convenience sample of 407 adults (enrolled from inpatient and outpatient settings
at five sites in the United States and ResearchMatch.org). Dimensionality testing
with confirmatory factor analysis preceded reliability testing. RESULTS: The Self
Care Maintenance scale (eight items, two dimensions: illness-related and health
promoting behaviour) fit well when tested with a two-factor confirmatory model.
The Self-Care Monitoring scale (five items, single factor) fitted well. The Self
Care Management scale (seven items, two factors: autonomous and consulting
behaviour), when tested with a two-factor confirmatory model, fitted adequately.
A simultaneous confirmatory factor analysis on the combined set of items
supported the more general model. CONCLUSION: The self-care of chronic illness
inventory is adequate in reliability and validity. We suggest further testing in
diverse populations of patients with chronic illnesses.
PMID- 29943402
TI - Dating igneous rocks using the Potassium-Argon Laser Experiment (KArLE)
instrument: A case study for ~380 Ma basaltic rocks.
AB - RATIONALE: We report new K-Ar isochron data for two ~380 Ma basaltic rocks, using
an updated version of the Potassium-Argon Laser Experiment (KArLE), which is
being developed for future in situ dating of planetary materials. These basalts
have K contents comparable with those of lunar KREEP basalts or igneous
lithologies found by Mars rovers, whereas previous proof-of-concept studies
focused primarily on more K-rich rocks. We aim to measure these analogous samples
to show the advancing capability of in situ K-Ar geochronology. METHODS:
Combining laser-induced breakdown spectroscopy (LIBS), mass spectrometry (MS),
and microscopic analyses, we measured the abundance of K and 40 Ar from 23 spots
on the basalt samples. We then constructed K-Ar isochron plots from these rocks.
The breadboard instrument consists of flight-equivalent devices including a 30-mJ
Nd:YAG laser and a quadrupole mass spectrometer. RESULTS: Despite much lower K
abundances than in previous studies, the isochron slopes yielded 380 +/- 44 Ma
and 398 +/- 50 Ma for 380.7-Ma and 373.5-Ma rocks, respectively, indicating that
accuracy better than 25 Ma (<7%) is achievable with our instrument. The isochron
intercepts both yielded trapped 40 Ar approximately 1 * 10-6 cm3 STP/g.
CONCLUSIONS: Our experimental results demonstrate that accurate and precise
measurements are possible using the KArLE approach on basaltic rocks, which are
ubiquitous on planetary surfaces, and are useful in addressing a wide range of
questions in planetary science.
PMID- 29943403
TI - Discrepancy between wrist-actigraph and polysomnographic measures of sleep in
patients with stable heart failure and a novel approach to evaluating
discrepancy.
AB - Wrist-actigraphy is often used to measure sleep characteristics in a variety of
populations, but discrepancies between actigraphic and polysomnographic measures
have been noted in populations experiencing poor sleep quality. The purpose of
this study is to examine the discrepancy between these measures and risk factors
for discrepancy in people with heart failure using a novel index. We used sleep
measures simultaneously recorded by actigraphy and polysomnography, and clinical
data from a cross-sectional study of 155 patients with heart failure (age = 60.5
[16.1] years; 65.2% male) recruited from evidence-based heart failure disease
management programmes. The discrepancy and consistency between the two measures
were evaluated using Bland-Altman plots, intra-class correlations and a newly
developed index that represents activity counts in wake episodes. Overall,
participants had short total sleep time (327.7 [95.9] min) and poor sleep
efficiency (71.3 [16.0]%) on polysomnography. The discrepancies between sleep
measures were small in patients less than 60 years old, and there was excellent
consistency (intra-class correlation = 0.81) compared with older patients who had
poorer consistency (intra-class correlation = 0.53) on total sleep time. Higher
daytime motor activity, poor sleep quality and more severe insomnia were
associated with smaller discrepancies in older, but not younger, patients, and
associations were more sensitively detected by the new index. These findings
suggest the importance of aging, disability and co-morbidity that may influence
motor activity from which sleep estimates are scored with actigraphy. The new
index may be useful in identifying factors associated with the correspondence
between actigraphy and polysomnography.
PMID- 29943404
TI - Boron-Substituted Coronene: Intriguing Geometric and Electronic Properties, and
Large Nonlinear Optical Response.
AB - By substituting boron atoms for selected carbon atoms of a graphene quantum dot
(GQD) model, namely a coronene molecule, the substituent effect on its geometric
and electronic structure, as well as nonlinear optical response has been
systemically investigated in theory. Our computations reveal that the boron
substitution leads to a similar noncentrosymmetric apophysis structure for the
boron-substituted coronene in singlet and triplet states. Noticeably, due to the
small energy difference of 2.5 kcal mol-1 between the singlet and triplet states,
the boron-substituted molecule can easily be switched between the
antiferromagnetic (singlet state) and ferromagnetic (triplet state) state by
slightly changing the external conditions. Notably, the boron-substituted
coronene exhibits a considerably large first hyperpolarizability of 36241 au,
because boron substitution yields a raised structure with an intermediate singlet
diradical character. Hence, it is expected that this study not only provides new
insights for the boron-substituent effect on the structure and properties of
graphene but also may promote practical applications of GQDs in the fields of
spintronics and nonlinear optics.
PMID- 29943405
TI - Microscopic considerations for optimizing silk biomaterials.
AB - Silk is an especially appealing biomaterial due to its adaptable mechanical
properties, allowing it to be used in a wide range of tissue engineering
applications. However, processing conditions play a critical role in determining
silk's mechanical properties, biodegradability, and biocompatibility. While bulk
properties of silk have been widely explored, focusing on microscopic features is
becoming increasingly important, as modifications at this scale largely affect
the resulting regenerative properties of the biomaterial. Structural changes
caused by the silk source, extraction, and processing should be carefully
considered, as they will affect the biocompatibility and degradability of silk
fibroin. Processing techniques and physical properties of silk that make it an
ideal material for many biomedical applications will be explored. This article is
categorized under: Implantable Materials and Surgical Technologies >
Nanotechnology in Tissue Repair and Replacement Implantable Materials and
Surgical Technologies > Nanomaterials and Implants.
PMID- 29943406
TI - Broken science and the failure of academics-resignation or reaction?
PMID- 29943407
TI - Mesenteric tumour deposits arising from small-intestine neuroendocrine tumours
are frequently associated with fibrosis and IgG4-expressing plasma cells.
AB - AIMS: Mesenteric tumour deposits frequently occur in small-intestine
neuroendocrine tumours. In many instances, these mesenteric tumour deposits are
surrounded by a dense fibrotic stroma and have associated lymphoplasmacytic
inflammation. The aim of this study was to examine whether mesenteric tumour
deposits in patients with small-intestine NETs neuroendocrine tumours show
histological and immunophenotypic overlap with IgG4-related sclerosing
mesenteritis. METHODS AND RESULTS: Sixty-six mesenteric tumour deposits from 66
patients with small-intestine neuroendocrine tumours with blocks available for
further studies were identified from our archives. Cases were assessed for
clinicopathological features and the presence of IgG4-positive and IgG-positive
plasma cells by immunohistochemistry. Ratios of IgG4-positive to IgG-positive
plasma cells were calculated. Seventeen mesenteric tumour deposits (26%) showed
>40 IgG4-positive plasma cells per high-power field, and the majority of cases
(68%) showed at least some staining of IgG4-positive plasma cells. Mesenteric
tumour deposits with >20 IgG4-positive plasma cells per high-power field tended
to be larger (25.9 +/- 13.0 mm versus 18.6 +/- 15.8 mm; P = 0.07), and had more
IgG-positive plasma cells (88 +/- 24 versus 36 +/- 37; P < 0.01) and a higher
IgG4-positive/IgG-positive plasma cell ratio (0.66 +/- 0.18 versus 0.17 +/- 0.25;
P < 0.01). All but one mesenteric tumour deposit with >20 IgG4-positve plasma
cells had a ratio of >40%. CONCLUSIONS: IgG4 expression is frequent in mesenteric
tumour deposits from small-intestine neuroendocrine tumours. Undersampling of
tumour on biopsies of mesenteric tumour deposits could potentially cause
diagnostic confusion with IgG4-related sclerosing mesenteritis.
PMID- 29943408
TI - The relationship between serum rheumatoid factor level and no-reflow phenomenon
in patients with acute ST-segment elevation myocardial infarction undergoing
primary percutaneous coronary intervention.
AB - OBJECTIVE: This study aimed to evaluate the relationship between serum rheumatoid
factor (RF) levels and no-reflow phenomenon in patients with acute ST-segment
elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary
intervention (PCI). METHODS: This single-center, cross-sectional study included a
total of 318 consecutive patients who were diagnosed with STEMI and underwent
primary PCI within 12 hours of the onset of symptoms. Baseline serum RF levels of
all patients were measured. The diagnosis of no-reflow phenomenon was defined as
a flow of TIMI II or less without the presence of dissection, mechanical
obstruction, significant residual stenosis, or other plausible causes. The
patients were divided into reflow group (n = 283) and no-reflow group (n = 46)
regarding the angiographic features of thrombolysis in myocardial infarction
(TIMI) flow of the infarct-related artery. RESULTS: No-reflow phenomenon was
observed in 13.8% of the patients. Median RF level was significantly higher in no
reflow group than in reflow group (18.5 (7.0-27.6) vs 8.0 (4.6-50.8), P < .001).
Forward conditional logistic regression analysis demonstrated that body mass
index (OR = 0.845, 95% CI: 0.765 to 0.933, P = .001), diabetes mellitus (OR =
5.257, 95% CI: 1.124 to 24.587, P = .035), baseline RF level (OR = 1.198, 95% CI:
1.108 to 1.295, P < .001), and SYNTAX score I (OR = 1.065, 95% CI: 1.025 to
1.107, P = .001) were the independent predictors of no-reflow phenomenon.
CONCLUSION: Baseline serum RF concentrations are independently associated with
the no-reflow phenomenon in patients undergoing primary PCI for acute STEMI.
PMID- 29943409
TI - Static to Dynamic: Kazan Chemists and the Transformation from Chemical Structure
to Reaction Regiochemistry.
AB - The Theory of Chemical Structure, first proposed independently by Friedrich
August Kekule and Archibald Scott Couper in 1858 was elaborated into a much more
useful tool for organic chemists by the Russian, Aleksandr Mikhailovich Butlerov,
the Professor of Chemistry at Kazan University. During the tenure of Butlerov,
and his mentors, Zinin and Klaus, Kazan became the pre-eminent school of
chemistry in the Russian empire. Butlerov's work firmly established structural
theory, and Butlerov confirmed its predictive value by predicting the structures
of alcohols and alkenes, and then completing their synthesis. Butlerov's student
(and disciple), Vladimir Vasil'evich Markovnikov, took Butlerov's work and
extended it, exploring the mutual influence of atoms in a molecule on the
properties of the compound. From this work, Markovnikov was able to formulate his
empirical rule for addition to alkenes.
PMID- 29943410
TI - Silver-doped graphite carbon nitride nanosheets as fluorescent probe for the
detection of curcumin.
AB - Green fluorescent silver (Ag)-doped graphite carbon nitride (Ag-g-C3 N4 )
nanosheets have been fabricated by an ultrasonic exfoliating method. The
fluorescence of the Ag-g-C3 N4 nanosheets is quenched by curcumin. The
fluorescence intensity decreases with the increase in the concentration of
curcumin, indicating that the Ag-g-C3 N4 nanosheets can function as a non-toxic
and facile fluorescence probe to detect curcumin. The fluorescence intensity of
Ag-g-C3 N4 nanosheets shows a linear relationship to curcumin in the
concentration range 0.01-2.00 MUM with a low detection limit of 38 nM. The
fluorescence quenching process between curcumin and Ag-g-C3 N4 nanosheets mainly
is based on static quenching. The fluorescent probe has been successfully applied
to analyse curcumin in human urine and serum samples with satisfactory results.
PMID- 29943411
TI - Silver nanoparticles: Electron transfer, reactive oxygen species, oxidative
stress, beneficial and toxicological effects. Mini review.
AB - The industry of nanotechnology has had a rapid development in the last decades.
In particular, silver nanoparticles (AgNPs) have unique properties so they can be
used in different industrial applications, mainly in areas such as electronics,
environment, medicine, biosensors and biotechnology; as well as household and
healthcare-related products, like cosmetics, due to their antimicrobial
properties. These beneficial effects are also offset by the higher chemical
reactivity of these NPs due to their surface area to volume ratio, leading to the
increased formation of reactive oxygen species (ROS) within cells. AgNPs,
however, have a dark side: they increase the formation of reactive oxygen species
(ROS). With increased human exposure to AgNPs, the risk and safety standards have
attracted much attention. This review highlights the beneficial and toxicological
effects of AgNPs in terms of cytotoxicity and genotoxicity.
PMID- 29943412
TI - Hierarchical Biomineralization: from Nature's Designs to Synthetic Materials for
Regenerative Medicine and Dentistry.
AB - Biomineralization is a highly dynamic, yet controlled, process that many living
creatures employ to develop functional tissues such as tooth enamel, bone, and
others. A major goal in materials science is to create bioinspired functional
structures based on the precise organization of building blocks across multiple
length scales. Therefore, learning how nature has evolved to use
biomineralization could inspire new ways to design and develop synthetic
hierarchical materials with enhanced functionality. Toward this goal, this review
dissects the current understanding of structure-function relationships of dental
enamel and bone using a materials science perspective and discusses a wide range
of synthetic technologies that aim to recreate their hierarchical organization
and functionality. Insights into how these strategies could be applied for
regenerative medicine and dentistry are also provided.
PMID- 29943413
TI - Nurse opinions about initiating spiritual conversation and prayer in patient
care.
AB - AIM: The aim of this study was to understand nurses' opinions about initiating
spiritual or religious conversation during patient care and to measure how these
perspectives are associated with demographic, religious and work-related
characteristics. BACKGROUND: Nurses are expected to provide spiritual care and do
so in diverse ways. Little is known about how nurses think about initiating
spiritual or religious discourse. DESIGN: Cross-sectional, quantitative. METHODS:
Online survey methods allowed data collection from 445 nurses. The survey,
accessed from the homepage of the Journal of Christian Nursing for 6 months
beginning June 2015, included scales measuring various facets of religiosity, and
items assessing nurse opinions about introducing spirituality or religion during
patient care and demographic and work-related variables. Variables showing
significant associations with Nurse Opinion items in bivariate analyses were
examined using binary logistic regression. RESULTS: About 90% of participants
believed it appropriate to initiate conversation about spirituality/religion and
nearly three-quarters thought it appropriate to self-disclose
spirituality/religion or offer prayer under certain circumstances or anytime. All
personal religiosity indicators except tentativeness of belief were found to be
associated with responses to Nurse Opinion items. That is, higher religiosity was
associated with opinion one could initiate such conversations, whereas lower
religiosity was associated with waiting for patients to initiate. Nurses working
in a faith-based organization were 276% more likely to believe they could
initiate such conversation and 153% more likely to think they could initiate an
offer of prayer. CONCLUSION: Nurse religiosity and work environment were
associated with nurse opinions about initiating spiritual/religious discourse
with patients.
PMID- 29943414
TI - Allergic contact dermatitis caused by benzyl salicylate in hair products.
PMID- 29943415
TI - Self-regulated learning in the clinical context: a systematic review.
AB - OBJECTIVES: Research has suggested beneficial effects of self-regulated learning
(SRL) for medical students' and residents' workplace-based learning. Ideally,
learners go through a cyclic process of setting learning goals, choosing learning
strategies and assessing progress towards goals. A clear overview of medical
students' and residents' successful key strategies, influential factors and
effective interventions to stimulate SRL in the workplace is missing. This
systematic review aims to provide an overview of and a theoretical base for
effective SRL strategies of medical students and residents for their learning in
the clinical context. METHODS: This systematic review was conducted according to
the guidelines of the Association for Medical Education in Europe. We
systematically searched PubMed, EMBASE, Web of Science, PsycINFO, ERIC and the
Cochrane Library from January 1992 to July 2016. Qualitative and quantitative
studies were included. Two reviewers independently performed the review process
and assessed the methodological quality of included studies. A total of 3341
publications were initially identified and 18 were included in the review.
RESULTS: We found diversity in the use of SRL strategies by medical students and
residents, which is linked to individual (goal setting), contextual (time
pressure, patient care and supervision) and social (supervisors and peers)
factors. Three types of intervention were identified (coaching, learning plans
and supportive tools). However, all interventions focused on goal setting and
monitoring and none on supporting self-evaluation. CONCLUSIONS: Self-regulated
learning in the clinical environment is a complex process that results from an
interaction between person and context. Future research should focus on
unravelling the process of SRL in the clinical context and specifically on how
medical students and residents assess their progress towards goals.
PMID- 29943417
TI - Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and
its residues in milk.
AB - Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human
and veterinary medicine. The aim of this study was to assess two major active
metabolites of MET, 4-methylaminoantipyrin (MAA) and 4-aminoantipyrin (AA), in
goat plasma after intravenous (IV) and intramuscular (IM) administration. In
addition, metabolite concentration in milk was monitored after IM injection. Six
healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a
crossover design study. The blood and milk samples were analyzed using HPLC
coupled with ultraviolet detector and the plasma vs concentration curves analyzed
by a noncompartmental model. In the goat, the MET rapidly converted into MAA and
the mean maximum concentration was 183.97 MUg/ml (at 0.08 hr) and 51.94 MUg/ml
(at 0.70 hr) after IV and IM administration, respectively. The area under the
curve and mean residual time values were higher in the IM than the IV
administered goats. The average concentration of AA was lower than MAA in both
groups. Over 1 MUg/ml of MAA was found in the milk (at 48 hr) after MET IM
administration. In conclusion, IM is considered to be a better administration
route in terms of its complete absorption with long persistence in the plasma.
However, this therapeutic option should be considered in light of the likelihood
of there being milk residue.
PMID- 29943416
TI - Efficient computation of the joint probability of multiple inherited risk alleles
from pedigree data.
AB - The Elston-Stewart peeling algorithm enables estimation of an individual's
probability of harboring germline risk alleles based on pedigree data, and serves
as the computational backbone of important genetic counseling tools. However, it
remains limited to the analysis of risk alleles at a small number of genetic loci
because its computing time grows exponentially with the number of loci
considered. We propose a novel, approximate version of this algorithm, dubbed the
peeling and paring algorithm, which scales polynomially in the number of loci.
This allows extending peeling-based models to include many genetic loci. The
algorithm creates a trade-off between accuracy and speed, and allows the user to
control this trade-off. We provide exact bounds on the approximation error and
evaluate it in realistic simulations. Results show that the loss of accuracy due
to the approximation is negligible in important applications. This algorithm will
improve genetic counseling tools by increasing the number of pathogenic risk
alleles that can be addressed. To illustrate we create an extended five genes
version of BRCAPRO, a widely used model for estimating the carrier probabilities
of BRCA1 and BRCA2 risk alleles and assess its computational properties.
PMID- 29943418
TI - Quantitative Determination of Contribution by Enhanced Local Electric Field,
Antenna-Amplified Light Scattering, and Surface Energy Transfer to the
Performance of Plasmonic Organic Solar Cells.
AB - Plasmonic metal nanostructures are widely used as subwavelength light
concentrators to enhance light harvesting of organic solar cells through two
photophysical effects, including enhanced local electric field (ELEF) and antenna
amplified light scattering (AALS), while their adverse quenching effect from
surface energy transfer (SET) should be suppressed. In this work, a comprehensive
study to unambiguously distinguish and quantitatively determine the specific
influence and contribution of each effect on the overall performance of organic
solar cells incorporated with Ag@SiO2 core-shell nanoparticles (NPs) is
presented. By investigating the photon conversion efficiency (PCE) as a function
of the SiO2 shell thickness, a strong competition between the ELEF and SET
effects in the performance of the devices with the NPs embedded in the active
layers is found, leading to a maximum PCE enhancement of 12.4% at the shell
thickness of 5 nm. The results give new insights into the fundamental
understanding of the photophysical mechanisms responsible for the performance
enhancement of plasmonic organic solar cells and provide important guidelines for
designing more-efficient plasmonic solar cells in general.
PMID- 29943419
TI - EIMS Fragmentation and MRM quantification of autoxidation products of alpha- and
beta-amyrins in natural samples.
AB - RATIONALE: Riverine particulate organic matter is generally considered to be
refractory with respect to further decomposition in the ocean. In order to check
the validity of this paradigm, there is a real need for tracers sufficiently
stable and specific to monitor the degradation of terrestrial higher plant
material in the environment. 3beta-hydroxy-urs-12-en-11-one and 3beta-hydroxy
olean-12-en-11-one (autoxidation products of alpha- and beta-amyrin) were
previously proposed for such use. METHODS: EIMS fragmentation pathways of 3beta
hydroxy-urs-12-en-11-one and 3beta-hydroxy-olean-12-en-11-one TMS derivatives
were investigated. These pathways were deduced by: (i) low energy CID-GC/MS/MS,
(ii) accurate mass measurement and (iii) deuterium labelling. Quantification of
these compounds in total lipid extracts of natural samples was then carried out
in MRM mode. RESULTS: CID-MS/MS analyses, accurate mass measurement and deuterium
labelling experiments allowed us to elucidate EIMS fragmentations of 3beta
hydroxy-urs-12-en-11-one and 3beta-hydroxy-olean-12-en-11-one TMS derivatives.
Some specific fragmentation pathways, useful in addition to chromatographic
retention times for further characterization, could be selected. As an
application of some of the described fragmentations, TMS derivatives of these
oxidation products were characterized and quantified in MRM mode in different
natural samples. CONCLUSIONS: EIMS fragmentations of 3beta-hydroxy-urs-12-en-11
one and 3beta-hydroxy-olean-12-en-11-one TMS derivatives exhibit specific
fragment ions, which appear to be very useful for the quantification of these
oxidation products in natural samples (riverine particulate matter, wet and dry
deposited atmospheric particles).
PMID- 29943420
TI - Hue discrimination among pathologists using a computer-based Farnsworth-Munsell
100-hue test.
PMID- 29943421
TI - Increased plasma prothrombin time is associated with poor prognosis in patients
with paraquat poisoning.
AB - BACKGROUND: Paraquat can cause severe injury to vascular endothelial cells and
lead to coagulation dysfunction when it is taken into the blood by oral
ingestion. In this study, we aim to find a routine coagulation index to serve as
an indicator of outcome in patients with acute paraquat poisoning. METHODS:
Between January 2012 and December 2016, 209 patients who attempted suicide by
oral ingestion of paraquat were admitted to the emergency room. Routine
coagulation indices, including plasma prothrombin time (PT), activated partial
thromboplastin time (APTT), fibrinogen (Fbg), thrombin time (TT), and D-dimer
were measured to analyze the trend of changes and their relationship with
prognosis. RESULTS: The results showed that the PT and APTT values in the >=30 mL
group were significantly greater than those in the <30 mL group (both P < .01).
Within 1 week of admission, PT and APTT values gradually decreased, while Fbg
levels gradually increased. Univariate and multivariate Cox regression analysis
indicated that sex, ingestion volume, and PT were independent predictors of
mortality within 40 days. The cumulative survival rates differed significantly (P
= .001) between patients with PT <12 seconds and PT >=12 seconds. CONCLUSIONS:
Coagulation status in patients with PQ poisoning was closely related to
prognosis. Routine monitoring of coagulation function, particularly PT in plasma,
is helpful for analysis of the condition and prognosis of patients with PQ
poisoning.
PMID- 29943422
TI - Tanshinone IIA effects on ovarian cancer cell line.
AB - OBJECTIVES: To explore the potential therapeutic effect of Tanshinone IIA against
ovarian cancer in vitro and elucidate the underlying molecular mechanism.
METHODS: The cell survival upon Tanshinone IIA treatment was determined by the
clonogenic assay. Cell apoptosis was analysed by Annexin V/propidium iodide
double staining. The cleaved caspase-3/poly ADP-ribose polymerase and apoptosis
related factors were quantified by Western blotting. The relative expression of
microRNAs (miRs) was determined by real-time polymerase chain reaction. KEY
FINDINGS: Tanshinone IIA treatment induced significant apoptosis in TOV-21G
cells. Tanshinone suppressed survivin expression while not affected Bax, Bcl-2
and Bcl-xL. We further predicted and experimentally confirmed overexpression of
miR-205 in TOV-21G, which ectopic significantly inhibited survivin and promoted
cell apoptosis. miR-205-specific antagonist completely abrogated the cell
suppressive effect of Tanshinone IIA. CONCLUSIONS: Our data suggested that
Tanshinone IIA induced cell apoptosis in ovarian carcinoma TOV-21G cells via
direct upregulation of miR-205. Our study highlighted the potential therapeutic
application of Tanshinone IIA against ovarian malignancy.
PMID- 29943423
TI - Partially Etched Ti3 AlC2 as a Promising High-Capacity Lithium-Ion Battery Anode.
AB - MXenes, a family of two-dimensional transition-metal carbide and nitride
materials, are thought to be promising materials in energy storage because of
their high electronic conductivity, hydrophilic surfaces, and low diffusion
barriers. MXenes are generally prepared by removing the "A" elements (A=Al, Si,
Sn, etc.) from their corresponding MAX phases by using hydrofluoric acid (HF) and
other etching agents, although these "A" elements usually have great volumetric
and gravimetric capacities. In a study of the etching progress of Ti3 AlC2 and
evaluation of their anode performance in lithium-ion batteries, a partially
etched sample (0.5 h-pe Ti3 C2 Tx ) is found to have much higher capacity (160
mAh g-1 , 331.6 mAh cm-3 at 1C) when compared with the fully etched Ti3 C2 Tx
(110 mAh g-1 , 190.3 mAh cm-3 at 1C). Moreover, a 99 % capacity retention was
observed even after 1000 cycles in the 0.5 h-pe Ti3 C2 Tx anode. This interesting
result can be explained, at least in part, by the alloying of the residual Al
during lithiation.
PMID- 29943425
TI - Royal Society of Chemistry Prizes and Awards 2018.
PMID- 29943424
TI - Beneficial effects of cilostazol on liver injury induced by common bile duct
ligation in rats: Role of SIRT1 signaling pathway.
AB - Liver fibrosis is a health challenge requiring alternative therapeutic
approaches. Cilostazol is a selective phosphodiesterase-3 inhibitor and possesses
antioxidant, anti-inflammatory and antifibrotic properties. Sirtuin 1 (SIRT1) is
a member of the silent information regulator 2 family. Cilostazol upregulates
SIRT1 expression. Cilostazol protects against the cholestatic liver insults
caused by bile duct obstruction. Involvement of SIRT1 pathway in this protective
effect has not been studied yet. So, we hypothesized that SIRT1 signaling may
have a role in cilostazol protective effects against bile duct ligation-induced
liver damages. Rats were subjected to common bile duct ligation then treated with
cilostazol (9 mg/kg or 27 mg/kg) in the presence or absence of specific SIRT1
inhibitor EX527. Cilostazol improved liver function, reduced inflammation,
enhanced antioxidant status, ameliorated cholestatic liver injury and upregulated
hepatic SIRT1. However, these protective effects were abrogated by EX527,
suggesting that SIRT1 signaling may have a role in these effects. In conclusion,
cilostazol in a dose-dependent way produced hepatoprotective effects via anti
inflammatory, antioxidant, antifibrotic effects which were mediated, in part,
through SIRT1 upregulation.
PMID- 29943426
TI - A novel cytochrome P450 mono-oxygenase from Streptomyces platensis resembles
activities of human drug metabolizing P450s.
AB - Cytochrome P450 mono-oxygenases (P450) are versatile enzymes which play essential
roles in C-source assimilation, secondary metabolism, and in degradations of endo
and exogenous xenobiotics. In humans, several P450 isoforms constitute the
largest part of phase I metabolizing enzymes and catalyze oxidation reactions
which convert lipophilic xenobiotics, including drugs, to more water soluble
species. Recombinant human P450s and microorganisms are applied in the
pharmaceutical industry for the synthesis of drug metabolites for
pharmacokinetics and toxicity studies. Compared to the membrane-bound eukaryotic
P450s, prokaryotic ones exhibit some advantageous features, such as high
stability and generally easier heterologous expression. Here, we describe a novel
P450 from Streptomyces platensis DSM 40041 classified as CYP107L that efficiently
converts several commercial drugs of various size and properties. This P450 was
identified by screening of actinobacterial strains for amodiaquine and ritonavir
metabolizing activities, followed by genome sequencing and expression of the
annotated S. platensis P450s in Escherichia coli. Performance of CYP107L in
biotransformations of amodiaquine, ritonavir, amitriptyline, and thioridazine
resembles activities of the main human metabolizing P450s, namely CYPs 3A4, 2C8,
2C19, and 2D6. For application in the pharmaceutical industry, an E. coli whole
cell biocatalyst expressing CYP107L was developed and evaluated for preparative
amodiaquine metabolite production.
PMID- 29943427
TI - Synthesis and biological evaluation of some new tricyclic pyrrolo[3,2
e]tetrazolo[1,5-c]pyrimidine derivatives as potential antitubercular agents.
AB - A series of new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines 8a-l were
synthesized and characterized by IR, NMR (1 H and 13 C), and mass spectral
analysis. The newly synthesized compounds 8a-l were inspected for their in vitro
antitubercular activity against Mycobacterium tuberculosis (MTB) H37 Ra using an
established XTT reduction menadione assay (XRMA). The title compounds exhibited
minimum inhibitory concentrations (MIC90 ) ranging from 0.09 to >30 MUg/mL. Five
compounds (8c, 8i-l) were further confirmed for their dose-dependent effect
against MTB. These compounds were evaluated in the THP-1 infection model, where
8i (MIC90 = 0.35 MUg/mL), 8j (MIC90 = 1.17 MUg/mL), 8k (MIC90 = 2.38 MUg/mL),
and 8l (MIC90 = 1.17 MUg/mL) demonstrated significant antitubercular activity.
All the ex vivo active compounds showed insignificant cytotoxicity against the
human cancer cell lines, HeLa, MCF-7, and THP-1. Inactivity of all these
compounds against Gram positive and Gram negative bacteria indicates their
specificity. Molecular docking studies in the active site of the sterol 14alpha
demethylase (CYP51) enzyme revealed a similar binding mode to the native ligand
in the crystal structure, thereby helping to understand the ligand-protein
interactions and to establish a structural basis for inhibition of MTB. The
results suggest novel pharmacophores as selective and specific inhibitors against
MTB that can be explored further to synthesize lead compounds against
tuberculosis. In summary, the results clearly indicate the identification of some
novel, selective, and specific inhibitors against MTB that can be explored
further for potential antitubercular drugs.
PMID- 29943429
TI - Triply Linked Porphyrinoids.
AB - Triply linked porphyrin arrays, so called porphyrin tapes, are intriguing
molecules in terms of their planar structures, far red-shifted absorption bands,
multi-charge storage abilities, and high conductivities. Recently, porphyrin tape
variants such as porphyrin-expanded porphyrin hybrid tapes, porphyrin arch-tapes,
corrole tapes, and a subporphyrin tape have been explored as novel pi-conjugated
materials. These new molecules exhibit electronic and structural characteristics
owing to direct triple linkages. This Minireview first discusses the fundamental
properties of the parent porphyrin tapes and the peripherally functionalized
porphyrin tapes. Then, a focus has been placed on the syntheses, structures, and
unique properties of the recently explored porphyrin tape variants.
PMID- 29943428
TI - Spontaneous development of Alzheimer's disease-associated brain pathology in a
Shugoshin-1 mouse cohesinopathy model.
AB - Spontaneous late-onset Alzheimer's disease (LOAD) accounts for more than 95% of
all human AD. As mice do not normally develop AD and as understanding on
molecular processes leading to spontaneous LOAD has been insufficient to
successfully model LOAD in mouse, no mouse model for LOAD has been available.
Existing mouse AD models are all early-onset AD (EOAD) models that rely on
forcible expression of AD-associated protein(s), which may not recapitulate
prerequisites for spontaneous LOAD. This limitation in AD modeling may contribute
to the high failure rate of AD drugs in clinical trials. In this study, we
hypothesized that genomic instability facilitates development of LOAD and tested
two genomic instability mice models in the brain pathology at the old age.
Shugoshin-1 (Sgo1) haploinsufficient (?) mice, a model of chromosome instability
(CIN) with chromosomal and centrosomal cohesinopathy, spontaneously exhibited a
major feature of AD pathology; amyloid beta accumulation that colocalized with
phosphorylated Tau, beta-secretase 1 (BACE), and mitotic marker phospho-Histone
H3 (p-H3) in the brain. Another CIN model, spindle checkpoint-defective BubR1-/+
haploinsufficient mice, did not exhibit the pathology at the same age, suggesting
the prolonged mitosis-origin of the AD pathology. RNA-seq identified ten
differentially expressed genes, among which seven genes have indicated
association with AD pathology or neuronal functions (e.g., ARC, EBF3). Thus, the
model represents a novel model that recapitulates spontaneous LOAD pathology in
mouse. The Sgo1-/+ mouse may serve as a novel tool for investigating mechanisms
of spontaneous progression of LOAD pathology, for early diagnosis markers, and
for drug development.
PMID- 29943430
TI - A bundled phosphate control intervention (4Ds) for adults with end-stage kidney
disease receiving haemodialysis: A cluster randomized controlled trial protocol.
AB - AIM: To evaluate the effectiveness of a bundled self-management intervention
(Taking control of your phosphate with the 4Ds) to improve phosphate control
among adults receiving haemodialysis. BACKGROUND: Hyperphosphataemia occurs in
end-stage kidney disease and is associated with increased morbidity and
mortality. While hyperphosphataemia can be managed through four methods (food,
drinks, drugs and dialysis) adherence to these methods is challenging for
patients. Studies also tend to focus on one method of phosphate control rather
than bundling all methods together into a theoretically driven intervention.
DESIGN: A multisite cluster randomized controlled trial with repeated measures.
METHODS: Adults receiving haemodialysis with high serum phosphate levels (>1.6
millimoles per litre for at least 3 months) will be cluster randomized to
standard care or intervention according to haemodialysis treatment shift.
Informed by social cognitive theory, the intervention focuses on improving self
efficacy and incorporates the "teach-back" method of patient education. The
intervention brings together essential phosphate control strategies of diet,
drinks, drugs (phosphate binders) and dialysis prescription in a 12-week self
management education programme. The primary outcome is serum phosphate level.
Secondary outcomes are knowledge of and adherence to phosphate control strategies
and self-efficacy for managing kidney disease. DISCUSSION: Efforts to improve
phosphate control have been undertaken although the optimal approach remains
unclear. This study will make an important contribution to building an evidence
base of phosphate control nursing intervention that can be delivered during
routine haemodialysis. TRIAL REGISTRATION: Australian and New Zealand Clinical
Trials Registry Number ACTRN12617000703303.
PMID- 29943432
TI - Synthesis and Antiviral Evaluation of TriPPPro-AbacavirTP, TriPPPro-CarbovirTP,
and Their 1',2'-cis-Disubstituted Analogues.
AB - Herein we describe the synthesis of lipophilic triphosphate prodrugs of abacavir,
carbovir, and their 1',2'-cis-substituted carbocyclic analogues. The 1',2'-cis
carbocyclic nucleosides were prepared by starting from enantiomerically pure
(1R,2S)-2-((benzyloxy)methyl)cyclopent-3-en-1-ol by a microwave-assisted
Mitsunobu-type reaction with 2-amino-6-chloropurine. All four nucleoside
analogues were prepared from their 2-amino-6-chloropurine precursors. The
nucleosides were converted into their corresponding nucleoside triphosphate
prodrugs (TriPPPro approach) by application of the H-phosphonate route. The
TriPPPro compounds were hydrolyzed in different media, in which the formation of
nucleoside triphosphates was proven. While the TriPPPro compounds of abacavir and
carbovir showed increased antiviral activity over their parent nucleoside, the
TriPPPro compounds of the 1',2'-cis-substituted analogues as well as their parent
nucleosides proved to be inactive against HIV.
PMID- 29943431
TI - Impact of Graphene on the Efficacy of Neuron Culture Substrates.
AB - How graphene influences the behavior of living cells or tissues remains a
critical issue for its application in biomedical studies, despite the general
acceptance that graphene is biocompatible. While direct contact between cells and
graphene is not a requirement for all biomedical applications, it is often
mandatory for biosensing. Therefore, it is important to clarify whether graphene
impedes the ability of cells to interact with biological elements in their
environment. Here, a systematic study is reported to determine whether applying
graphene on top of matrix substrates masks interactions between these substrates
and retinal ganglion cells (RGCs). Six different platforms are tested for primary
RGC cultures with three platforms comprised of matrix substrates compatible with
these neurons, and another three having a layer of graphene placed on top of the
matrix substrates. The results demonstrate that graphene does not impede
interactions between RGCs and underlying substrate matrix, such that their
positive or negative effects on neuron viability and vitality are retained.
However, direct contact between RGCs and graphene reduces the number, but
increases basal activity, of functional cation channels. The data indicate that,
when proper baselines are established, graphene is a promising biosensing
material for in vitro applications in neuroscience.
PMID- 29943433
TI - Synthesis of Bare Iron Nanoparticles from Ferrocene Hexane Solution by
Femtosecond Laser Pulses.
AB - Iron-based nanoparticles (FeNPs) have unique and attractive properties such as
superparamagnetism, biocompatibility, and catalytic activity. Although the
synthesis of precious metal NPs from a metal in liquid and/or metal salt solution
by a pulsed laser has been investigated, comparably little effort has been
devoted to examine the production of FeNPs. Here we report the synthesis of
carbon-shell free spherical NPs of iron oxide (magnetite) from ferrocene hexane
solution by femtosecond near infrared laser pulses. Nanosecond UV laser pulses
are used to compare the evolution of the particle size distribution as a function
of laser irradiation time. The size of NPs remains constant even for extended
exposure to femtosecond laser pulses, whereas it grows with exposure to
nanosecond laser pulses. The primary particles are generated by photochemical
reactions regardless of pulse duration; however, the fragmentation of NPs by
successive femtosecond laser pulses regulates the particle size.
PMID- 29943434
TI - Bayesian applications in pharmaceutical statistics.
PMID- 29943435
TI - Differences in the persistence of spatial memory deficits induced by a chronic
stressor in adolescents compared to juveniles.
AB - Adolescence is thought of as a stress-sensitive developmental period. While many
studies have compared adolescent responses to stress relative to that of adults,
a growing body of work has examined stress responses in juveniles. Here we
investigated if a chronic stressor has a differential effect on spatial memory in
rats depending on whether it occurs during adolescence or the juvenile period.
Male rats were exposed to the stress hormone corticosterone (Cort) in their
drinking water, a vehicle control (2.5% ethanol), or water, for 7 days before
being tested on a novel Object/Place task 6 days or 6 weeks later. Exposure to
Cort or ethanol at either age impaired spatial memory at the 6-day test. The
ethanol induced impairment was attenuated 6 weeks later. However, rats given Cort
during adolescence, but not the juvenile period, were still impaired. Together,
these results suggest that adolescence is indeed a stress-sensitive period.
PMID- 29943436
TI - Can't Ignore-Distraction by Task-Irrelevant Sounds in Early and Middle Childhood.
AB - Attention control abilities are relevant for learning success. Little is known
about the development of audio-visual attention in early childhood. Four groups
of children between the ages of 4 and 10 years and adults performed an audio
visual distraction paradigm (N = 106). Multilevel analyses revealed increased
reaction times in a visual categorization task when task-irrelevant novel sounds
were presented, demonstrating involuntary distraction of attention. This
distraction effect decreased with age and significantly differed between age
groups. In addition, the two youngest age groups responded with a delay in trials
following a distractor trial, indicating delayed reallocation of attention to the
task at hand. Results indicate a significant maturation of audio-visual attention
control within a few years during early childhood that continues throughout
middle childhood.
PMID- 29943437
TI - Skeletal unit construction of rat mandible based on the masticatory muscle
anatomy and double microcomputed tomography.
AB - This study aimed to divide the mandible into skeletal units based on three
dimensional (3D) muscular anatomy with microcomputed tomography (micro-CT) of
Sprague-Dawley rat. Five normal rats were micro-CT scanned at 12 weeks of age
before and after contrast enhancements for the masticatory muscles. Three
dimensional reconstruction of the mandible was performed from the initial micro
CT images, followed by segmentation of the masticatory muscles using the second
enhanced micro-CT data. Bone and muscle models were superimposed based on the
teeth and bony structures to evaluate muscular orientation and attachment. The
mandible was divided into skeletal units using the bony structures and muscle
attachments. The mandibular foramen and mental foramen were adopted as the
reference points based on their anatomical and developmental significance. The
skeletal units consisted of the condylar, coronoid, angular, body and symphyseal
units. Further evaluation of these units in relation to development, growth, and
other biology and medicine will be helpful in elucidating their biological
identities.
PMID- 29943438
TI - How a System of Checks on Symbiosis Could Become Disastrous.
PMID- 29943439
TI - Sex Differences in Early Embryogenesis: Inter-Chromosomal Regulation Sets the
Stage for Sex-Biased Gene Networks: The dialogue between the sex chromosomes and
autosomes imposes sexual identity soon after fertilization.
AB - Sex-specific transcriptional and epigenomic profiles are detectable in the embryo
very soon after fertilization. I propose that in male (XY) and female (XX) pre
implantation embryos sex chromosomes establish sexually dimorphic interactions
with the autosomes, before overt differences become apparent and long before
gonadogenesis. Lineage determination restricts expression biases between the
sexes, but the epigenetic differences are less constrained and can be
perpetuated, accounting for dimorphisms that arise later in life. In this way,
sexual identity is registered in the epigenome very early in development. As
development progresses, sex-specific regulatory modules are harbored within
shared transcriptional networks that delineate common traits. In reviewing this
field, I propose that analyzing the mechanisms for sexual dimorphisms at the
molecular and biochemical level and incorporating developmental and environmental
factors will lead to a greater understanding of sex differences in health and
disease. Also see the video abstract here: https://youtu.be/9BPlbrHtkHQ.
PMID- 29943440
TI - Penalized spline smoothing using Kaplan-Meier weights with censored data.
AB - In this paper, we consider the problem of nonparametric curve fitting in the
specific context of censored data. We propose an extension of the penalized
splines approach using Kaplan-Meier weights to take into account the effect of
censorship and generalized cross-validation techniques to choose the smoothing
parameter adapted to the case of censored samples. Using various simulation
studies, we analyze the effectiveness of the censored penalized splines method
proposed and show that the performance is quite satisfactory. We have extended
this proposal to a generalized additive models (GAM) framework introducing a
correction of the censorship effect, thus enabling more complex models to be
estimated immediately. A real dataset from Stanford Heart Transplant data is also
used to illustrate the methodology proposed, which is shown to be a good
alternative when the probability distribution for the response variable and the
functional form are not known in censored regression models.
PMID- 29943441
TI - Bayesian variable selection logistic regression with paired proteomic
measurements.
AB - We explore the problem of variable selection in a case-control setting with mass
spectrometry proteomic data consisting of paired measurements. Each pair
corresponds to a distinct isotope cluster and each component within pair
represents a summary of isotopic expression based on either the intensity or the
shape of the cluster. Our objective is to identify a collection of isotope
clusters associated with the disease outcome and at the same time assess the
predictive added-value of shape beyond intensity while maintaining predictive
performance. We propose a Bayesian model that exploits the paired structure of
our data and utilizes prior information on the relative predictive power of each
source by introducing multiple layers of selection. This allows us to make
simultaneous inference on which are the most informative pairs and for which-and
to what extent-shape has a complementary value in separating the two groups. We
evaluate the Bayesian model on pancreatic cancer data. Results from the fitted
model show that most predictive potential is achieved with a subset of just six
(out of 1289) pairs while the contribution of the intensity components is much
higher than the shape components. To demonstrate how the method behaves under a
controlled setting we consider a simulation study. Results from this study
indicate that the proposed approach can successfully select the truly predictive
pairs and accurately estimate the effects of both components although, in some
cases, the model tends to overestimate the inclusion probability of the second
component.
PMID- 29943442
TI - Calendar time as an instrumental variable in assessing the risk of heart failure
with antihyperglycemic drugs.
AB - OBJECTIVE: In recent years, second-line diabetes treatment with dipeptidyl
peptidase-4 inhibitors (DPP-4i) increased with a corresponding decrease in
thiazolidinediones (TZDs). Using hospitalization for heart failure (HF) as a
positive control outcome, we explored the use of calendar time as an instrumental
variable (IV) and compared this approach to an active comparator new-user study.
METHODS: We identified DPP-4i or TZD initiators after a 6-month washout using
Medicare claims 2006-2013. The IV was defined as a binary variable comparing
initiators during October 2010 to December 2013 (postperiod) versus January 2008
to May 2010 (preperiod). We examined IV strength and estimated risk differences
(RDs) for HF using Kaplan-Meier curves, which were compared with propensity score
(PS)-weighted RD for DPP-4i versus TZD. RESULTS: The IV compared 22 696
initiators (78% DPP-4i) in the postperiod versus 20 283 initiators (38% DPP-4i)
in the preperiod, resulting in 40% compliance. The active-comparator (PS
weighted) approach compared 26 198 DPP-4i and 18 842 TZD initiators. Covariate
balance across IV levels was slightly better than across treatments (standardized
difference, 3% vs 4.5%). The 1- and 2-year local average treatment effects of RD
of HF per 100 patients in the "compliers" (95% confidence intervals) were -0.62 (
0.99 to -0.25) and -0.88 (-1.46 to -0.25). Corresponding PS-weighted results were
-0.20 (-0.33 to -0.05) and -0.18 (-0.30 to 0.03). CONCLUSION: Both approaches
indicated lesser risk of HF hospitalizations among DPP-4i vs TZD initiators. The
magnitude of the estimated effects may differ due to differences in the target
populations and assumptions. Calendar time can be leveraged as an IV when market
dynamics lead to profound changes in treatments.
PMID- 29943443
TI - Estimating plate-based model food proportions in adults living in Scotland using
short dietary assessment questionnaires.
AB - AIM: To determine whether a food frequency questionnaire (FFQ) and a short
dietary assessment tool can be used to accurately estimate the Eatwell Guide
proportions (a plate-based food model) of diets of adults living in Scotland.
METHODS: The cross-sectional study was conducted as a follow up of the 2010
Scottish Health Survey (participants aged 18-65 years old). Proportions of the
Eatwell Guide food groups (starchy carbohydrates, fruits and vegetables (F&V),
dairy and alternatives, protein foods and oils and spreads) were calculated from
the Scottish Health Survey Eating Habits Module (SHeS EHM), Scottish
Collaborative Group FFQ (SCG FFQ) and a seven-day estimated food diary (reference
method), and compared using the Aitchison method and Wilcoxon Signed-Rank Test.
Bland-Altman analyses assessed mean difference and 95% limits of agreement
between the methods for each food group. RESULTS: Ninety-six adults were included
(mean (SD) age = 51.4 (11.1) years; body mass index = 27.1 (4.9) kg/m2 ; 58%
female). The SCG FFQ scored a lower median Aitchison distance (1.47) than the
SHeS EHM (1.99) (P < 0.001), showing greater agreement with the reference method
(P < 0.001). Bland-Altman plots also showed better agreement for the SCG FFQ than
the SHeS EHM. Poorest agreement was for starchy carbohydrates (both methods),
protein foods (SHeS EHM) and dairy (SCG FFQ). CONCLUSIONS: The SCG FFQ could be
used to estimate Eatwell Guide proportions and monitor compliance to the Eatwell
Guide recommendations and could be improved with small changes. The SHeS EHM is
less suitable, but additional questions on dairy foods, and oils and spreads
would improve its ability to estimate the Eatwell Guide proportions.
PMID- 29943444
TI - Epoxy-Functional Sterically Stabilized Diblock Copolymer Nanoparticles via RAFT
Aqueous Emulsion Polymerization: Comparison of Two Synthetic Strategies.
AB - Polymerization-induced self-assembly (PISA) is a powerful and versatile technique
for the synthesis of a wide range of sterically stabilized diblock copolymer nano
objects. Recently, PISA has been used to prepare epoxy-functional diblock
copolymer worms and spheres directly in aqueous solution by incorporating
glycidyl methacrylate (GlyMA) into the core-forming hydrophobic block. Herein,
the synthesis of diblock copolymer spheres via reversible addition-fragmentation
chain transfer (RAFT) aqueous emulsion polymerization of benzyl methacrylate is
examined, in which the epoxy groups are exclusively located within a non-ionic
poly(glycerol monomethacrylate)-based stabilizer block. Two synthetic strategies
are explored: i) using an epoxy-functional RAFT chain transfer agent (CTA) to
place an epoxy group at the terminus of every stabilizer block and ii)
incorporation of ~1 epoxy group per stabilizer chain via copolymerization of
GlyMA with glycerol monomethacrylate (GMA). The epoxy groups conferred by the
GlyMA comonomer are significantly more resistant to hydrolysis than those
introduced using the epoxy-functional RAFT CTA. The epoxy-functional
nanoparticles are subsequently reacted with various water-soluble thiols to
modify their electrophoretic behavior. Such nanoparticles are expected to offer
potential applications in the context of mucoadhesion.
PMID- 29943445
TI - Ratings surveillance and reliability in a study of major depressive disorder with
subthreshold hypomania (mixed features).
AB - OBJECTIVES: Site-independent ratings surveillance assessed ratings reliability in
a clinical trial. METHODS: Inter-rater reliability was assessed at the screen
visit in a 6-week, double-blind, placebo-controlled study of lurasidone for the
treatment of major depressive disorder (MDD) with subthreshold hypomanic
("mixed") symptoms (clinicaltrials.gov NCT01421134). Site-based Montgomery-Asberg
Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) interviews
were paired with 184 site-independent ratings derived from audio-digital
recordings. RESULTS: The paired MADRS and YMRS scores were highly correlated (r =
0.708 and 0.885, respectively) and generated minimal scoring discordance. The
surveillance program identified 14 MADRS scores (7.6% of this sample) that were
below the study entry criterion (MADRS >=26) and resulted in screen failure. When
present, paired scoring discordance was associated with symptom severity,
interview length, interview quality, and the level of patient cooperation. Higher
severity scores (MADRS >=40 and YMRS >=15) were associated with greater paired
scoring discordance. Further, MADRS scores <30 and short MADRS interviews
conducted in <=12 min revealed significantly more pairs of discordant outliers (p
= 0.04 and 0.009, respectively). CONCLUSIONS: The findings suggest that MDD
patients with mixed features can be reliably assessed, that paired site-based and
site-independent assessments were generally concordant, and that ratings
surveillance may reinforce ratings precision.
PMID- 29943446
TI - How Low Can You Go? Low Densities of Poly(ethylene glycol) Surfactants Attract
Stealth Proteins.
AB - It is now well-established that the surface chemistry and "stealth" surface
functionalities such as poly(ethylene glycol) (PEG) chains of nanocarriers play
an important role to decrease unspecific protein adsorption of opsonizing
proteins, to increase the enrichment of specific stealth proteins, and to prolong
the circulation times of the nanocarriers. At the same time, PEG chains are used
to provide colloidal stability for the nanoparticles. However, it is not clear
how the chain length and density influence the unspecific and specific protein
adsorption keeping at the same time the stability of the nanoparticles in a
biological environment. Therefore, this study aims at characterizing the protein
adsorption patterns depending on PEG chain length and density to define limits
for the amount of PEG needed for a stealth effect by selective protein adsorption
as well as colloidal stability during cell experiments. PEG chains are introduced
using the PEGylated Lutensol AT surfactants, which allow easy modification of the
nanoparticle surface. These findings indicate that a specific enrichment of
stealth proteins already occurs at low PEG concentrations; for the decrease of
unspecific protein adsorption and finally the colloidal stability a full surface
coverage is advised.
PMID- 29943447
TI - Text messaging improves preoperative exercise in patients undergoing bariatric
surgery.
AB - BACKGROUND: To investigate whether a text message intervention improves adherence
to preoperative exercise advice prior to laparoscopic sleeve gastrectomy (LSG).
METHODS: A single-blinded parallel design 1:1 ratio randomized controlled trial
was performed in patients undergoing LSG as a single-stage bariatric procedure
for morbid obesity. The intervention group received preoperative daily text
messages. The primary outcome was adherence to preoperative exercise advice as
assessed by the number of participants partaking in >=450 metabolic equivalent
minutes (METmin-1 ) exercise activity per week preoperatively. RESULTS: Eighty
eight patients were included in the analysis with 44 allocated to each arm.
Adherence and exercise activity increased significantly from baseline in the
exposure group (EG) but not in the control group (CG). Adherence was
significantly higher in the EG at the end of the intervention period compared to
the CG. Despite increased exercise activity, there was no improvement in 6-min
walk test or surgical recovery. CONCLUSION: A daily text message intervention
improved adherence to preoperative exercise advice, but this did not correlate
with improved surgical recovery.
PMID- 29943448
TI - Advancing microbiome research.
PMID- 29943449
TI - Basalt fibers grafted with a poly(ionic liquids) coating for in-tube solid-phase
microextraction.
AB - To improve the durability and extraction efficiency of an ionic liquid coating, 1
dodecyl-3-vinylimidazolium bromide was polymerized and grafted onto basalt fibers
for in-tube solid-phase microextraction. To develop an extraction tube, basalt
fibers grafted with the poly(ionic liquids) coating were filled into a polyether
ether ketone tube with a 0.75 mm inner diameter. The extraction tube was
connected to high-performance liquid chromatography system equipped with a
sampling pump to build an online enrichment and analysis system. Using four
common phthalates as model analytes, the extraction tube was investigated by the
online analysis system. Good enrichment performance was exhibited by high
enrichment factors ranging from 851 to 1858. Under the optimum conditions, an
online analysis method was established, and good linearity (0.03-12 and 0.15-12
MUg/L) and low limits of detection (0.01-0.05 MUg/L) were achieved. This analysis
method was applied to real samples including water in a disposable plastic box
and the bottled water, some targets were detected but not quantified, and the
relative recoveries spiked at 2, 5 and 10 MUg/L were in the range of 86.4-119.5%.
PMID- 29943450
TI - Filter-based emulsification microextraction as an efficient method for the
determination of chlorophenols by gas chromatography.
AB - In this work, an efficient microextraction method was applied for the extraction
of some chlorophenols in water samples. This method, termed filter-based
emulsification microextraction, is based on the dispersion of an extractant into
an aqueous sample solution to accelerate the extraction process and the
utilization of a Nylon syringe filter to break the emulsion. After phase
separation, the method is coupled with gas chromatography as a final analyzer
instrument. The overall derivatization/extraction time was about 90 s. The
proposed method is centrifuge-free, and it also provides a suitable sample clean
up by filtration of the extracting phase. The effective parameters involved in
the extraction method were optimized. Under the optimal experimental conditions,
the method provided a good linearity in the range of 2.0-2000 ng/mL, extraction
repeatabilities (relative standard deviations) below 9.4%, enrichment factors of
180-203, and limits of detection between 0.5 and 1.2 ng/mL.
PMID- 29943451
TI - Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous
treatment of absence status epilepticus.
AB - OBJECTIVE: The objective of this study was to evaluate effectiveness, retention,
and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in
clinical practice. METHODS: A multicenter, retrospective cohort study recruiting
all patients that started BRV in 2016 and 2017. RESULTS: A total of 61 patients
(mean age = 29.8, range = 9-90 years, 41 female [67%]) were treated with BRV.
They were difficult to control, with 2.4 failed antiepileptic drugs (AEDs) in the
past, taking 1.9 AEDs on average at baseline. The length of exposure to BRV
ranged from 7 days to 24 months, with a mean retention time of 7.9 months,
resulting in a total exposure time to BRV of 483 months. The retention rate was
82% at 3 months and 69% at 6 months. Efficacy at 3 months was 36% (50% responder
rate), with 25% seizure-free for 3 months. Patients with juvenile myoclonic
epilepsy showed a responder rate of 60%, with 40% being free of any seizures.
Long-term 50% responder rate was present in 17 patients (28%; 11 seizure-free
[18%]) for >6 months and in 14 patients (23%; 10 seizure-free [16%]) for >12
months. Treatment-emergent adverse events were observed in 26% of the patients,
with the most common being somnolence, ataxia, and psychobehavioral adverse
events. Use of intravenous BRV with bolus injection of 200-300 mg in two females
with absence status epilepticus was well tolerated, but did not result in
cessation of status epilepticus. SIGNIFICANCE: Use of BRV in GGE is well
tolerated, and 50% responder rates are similar to those observed in the
regulatory trials for focal epilepsies. An immediate switch from levetiracetam
(LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral
adverse events seems less prominent than under LEV, and a switch to BRV can be
considered in patients with LEV-induced adverse events.
PMID- 29943452
TI - Cardiac effects of acute administration of a protonophore in a rat model.
AB - OBJECTIVES: Excessive use of uncoupling agents, previously used as weight loss
agents, has led to the increase in body temperature and death. The aim of the
present study was to evaluate the acute cardiac effects of mitochondrial
protonophore in a rat model at a high dose, and its specific influence on cardiac
substrate uptake. METHODS: Eight-week-old male Sprague-Dawley rats were
intraperitoneally injected with the protonophore carbonyl cyanide m-chloro phenyl
hydrazone (CCCP; 4 mg/kg) or vehicle (dimethyl sulfoxide). Blood pressure, heart
rate (HR) and systolic function were recorded. Substrate uptake was monitored by
radioactive tracers. KEY FINDINGS: Compared to the control group, the respiratory
rate and body temperature increased, the left ventricle was dilated, and systolic
function transiently deteriorated in the CCCP group. There was no difference in
blood pressure and HR between the two groups. In cardiac substrate uptake,
glucose uptake showed a 95% increase (P < 0.05), and fatty acid uptake showed a
52% decrease (P < 0.05) in CCCP-administered group. CONCLUSIONS: The deleterious
effects on cardiac function and the changes in substrate uptake were observed
when administered with the protonophore at a high dose.
PMID- 29943453
TI - Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor
therapy: A spectrum of immune reactions from paraneoplastic pemphigus-like to
Grover-like lesions.
AB - Checkpoint inhibitors (CPIs) restore the function of effector immunocytes to
target and destroy cancer cells. Immune-related adverse events (irAEs) are a
consequence of immune reactivation, with unpredictable inflammatory response,
loss of self-tolerance, and development of autoimmunity. Adverse events from CPIs
that present as dermatologic toxicities have diverse clinical and histopathologic
features. CPI-associated dermatologic toxicities may exhibit histopathologic
features of lichenoid dermatitis, bullous pemphigoid, and granulomatous/sarcoid
like reactions. Suprabasal acantholytic dermatologic toxicities associated with
CPIs are particularly rare but represent an emerging histopathologic pattern and
include lichenoid dermatitis with suprabasal acantholysis/vesicle formation to
Grover disease (transient acantholytic dermatosis). Here, we report two patients
who developed suprabasal acantholytic dermatologic toxicities during CPI therapy.
One patient exhibited a CPI-associated autoimmune blistering disease with
paraneoplastic pemphigus (PNP)-like features restricted to histopathology and
immunofluorescence, while the other patient had Grover-like lesions. A review of
the literature revealed a spectrum of suprabasal acantholytic dermatologic
toxicities associated CPIs that may present as lichenoid dermatitis with
acantholysis/vesicle formation, Grover-like eruptions, and lesions with PNP-like
features restricted to histopathology and immunofluorescence. It is important for
clinicians and pathologists to recognize the types of dermatologic toxicities
associated with CPIs to direct appropriate therapeutic strategies.
PMID- 29943454
TI - Phosphoryl-Transfer Reaction in RNA under Alkaline Conditions.
AB - The phosphoryl-transfer reaction in RNA under alkaline conditions by exploring
the influence of several solvents theoretically was studied. The calculations
were carried out by using the M06-2X functional and the solvents were taken as a
continuum by using the solvent model density (SMD) method. The main findings show
that the O2'-P-O5' angle in the reactants, the free activation energies, and the
reaction mechanism are clearly dependent on the dielectric constant of the
environment, thus showing that the electrostatic term is the determining factor
for this chemical system with two negative charges. Our study seems to indicate
that water, the solvent with the greatest dielectric constant, would be the
solvent that increases the reaction rate the most. As this outcome was not the
case in enzymatic catalysis, one has to conclude that, in the case of proteins as
well as for ribozymes, the enzymatic catalysis is not mainly due to the solvent
reaction field, but to local electrical fields as a result of enzyme
preorganization.
PMID- 29943455
TI - Family physician remuneration schemes and specialist referrals: Quasi
experimental evidence from Ontario, Canada.
AB - Understanding how family physicians respond to incentives from remuneration
schemes is a central theme in the literature. One understudied aspect is
referrals to specialists. Although the theoretical literature has suggested that
capitation increases referrals to specialists, the empirical evidence is mixed.
We push forward the empirical research on this question by studying family
physicians who switched from blended fee-for-service to blended capitation in
Ontario, Canada. Using several health administrative databases from 2005 to 2013,
we rely on inverse probability weighting with fixed-effects regression models to
account for observed and unobserved differences between the switchers and
nonswitchers. Switching from blended fee-for-service to blended capitation
increases referrals to specialists by about 5% to 7% per annum. The cost of
specialist referrals is about 7 to 9% higher in the blended capitation model
relative to the blended fee-for-service. These results are generally robust to a
variety of alternative model specifications and matching techniques, suggesting
that they are driven partly by the incentive effect of remuneration. Policy
makers need to consider the benefits of capitation payment scheme against the
unintended consequences of higher referrals to specialists.
PMID- 29943456
TI - Land-atmospheric feedbacks during droughts and heatwaves: state of the science
and current challenges.
AB - Droughts and heatwaves cause agricultural loss, forest mortality, and drinking
water scarcity, especially when they occur simultaneously as combined events.
Their predicted increase in recurrence and intensity poses serious threats to
future food security. Still today, the knowledge of how droughts and heatwaves
start and evolve remains limited, and so does our understanding of how climate
change may affect them. Droughts and heatwaves have been suggested to intensify
and propagate via land-atmosphere feedbacks. However, a global capacity to
observe these processes is still lacking, and climate and forecast models are
immature when it comes to representing the influences of land on temperature and
rainfall. Key open questions remain in our goal to uncover the real importance of
these feedbacks: What is the impact of the extreme meteorological conditions on
ecosystem evaporation? How do these anomalies regulate the atmospheric boundary
layer state (event self-intensification) and contribute to the inflow of heat and
moisture to other regions (event self-propagation)? Can this knowledge on the
role of land feedbacks, when available, be exploited to develop geo-engineering
mitigation strategies that prevent these events from aggravating during their
early stages? The goal of our perspective is not to present a convincing answer
to these questions, but to assess the scientific progress to date, while
highlighting new and innovative avenues to keep advancing our understanding in
the future.
PMID- 29943457
TI - Insights in a novel gram-positive type IV secretion system.
PMID- 29943458
TI - Topical proline therapy in prolidase deficiency.
PMID- 29943460
TI - Clinical characteristics of early onset anorexia nervosa.
AB - The aim of the current paper is to evaluate clinical characteristics of 30
children with early onset anorexia nervosa (EO-AN; age = 12.2 +/- 1.6 years)
compared with 30 patients with adolescent onset AN (AO-AN; age = 15.9 +/- 0.7
years) and 60 age-matched healthy controls. Statistical analyses included one-way
analyses of variance with three planned comparisons and chi-square tests.
Compared with AO-AN, EO-AN patients displayed more restrictive eating behaviour
(p = 0.038), received more tube-feeding (p = 0.024), and had less problems with
self-esteem (p < 0.001) and perfectionism (p = 0.001). EO-AN patients have
similar eating disorder pathology (p = 0.183), body-image distortion (p = 0.060),
and number of hospitalizations (p = 0.358) as AO-AN. Only a third of EO-AN
patients suffer from low self-esteem. Overall, core AN pathology seems similar in
EO-AN and AO-AN. However, EO-AN patients show differences in their pathological
eating behaviour and the need for tube-feeding.
PMID- 29943459
TI - Regulation of contact sensitivity in non-obese diabetic (NOD) mice by innate
immunity.
AB - BACKGROUND: Genetic background influences allergic immune responses to
environmental stimuli. Non-obese diabetic (NOD) mice are highly susceptible to
environmental stimuli. Little is known about the interaction of autoimmune
genetic factors with innate immunity in allergies, especially skin
hypersensitivity. OBJECTIVES: To study the interplay of innate immunity and
autoimmune genetic factors in contact hypersensitivity (CHS) by using various
innate immunity-deficient NOD mice. METHODS: Toll-like receptor (TLR) 2
deficient, TLR9-deficient and MyD88-deficient NOD mice were used to investigate
CHS. The cellular mechanism was determined by flow cytometry in vitro and
adoptive cell transfer in vivo. To investigate the role of MyD88 in dendritic
cells (DCs) in CHS, we also used CD11cMyD88+ MyD88-/- NOD mice, in which MyD88
is expressed only in CD11c+ cells. RESULTS: We found that innate immunity
negatively regulates CHS, as innate immunity-deficient NOD mice developed
exacerbated CHS accompanied by increased numbers of skin-migrating CD11c+ DCs
expressing higher levels of major histocompatibility complex II and CD80.
Moreover, MyD88-/- NOD mice had increased numbers of CD11c+ CD207- CD103+ DCs
and activated T effector cells in the skin-draining lymph nodes. Strikingly, re
expression of MyD88 in CD11c+ DCs (CD11cMyD88+ MyD88-/- NOD mice) restored hyper
CHS to a normal level in MyD88-/- NOD mice. CONCLUSION: Our results suggest that
the autoimmune-prone NOD genetic background aggravates CHS regulated by innate
immunity, through DCs and T effector cells.
PMID- 29943461
TI - Protective effect of skin-derived precursors on photoaging in nude mice.
AB - OBJECTIVES: Currently, innovative methods to prevent photoaging are needed. Skin
derived precursors (SKP) have been shown to play a crucial role in resisting UVB
induced apoptosis in vitro. The objective of this study was to explore the effect
of SKP on preventing skin photoaging in vivo. METHODS: Skin-derived precursors
from neonatal BALB/c mice were isolated, identified and intradermally
transplanted with a PKH26 label to track their survival. These were then injected
at different concentrations into the buttock dermis of nude mice at 2-weekly
intervals before UV irradiation. Photographs, assessment of live skin surface,
histology with quantitative real-time polymerase chain reaction and
immunohistochemistry were used to evaluate the impact of SKP on wrinkles and
other relevant indicators of skin photoaging. RESULTS: SKP exhibited a sphere
like structure and could survive for at least 2 weeks after intradermal
transplantation. A large dose of SKP transplantation (105 SKP +UV) at 2-weekly
intervals were able to ameliorate coarse UV-induced wrinkles. Moreover, the skin
smoothness value, dermal thickness and collagen percentage were significantly
increased in mice that received a large dose of SKP (105 SKP +UV). UV radiation
induced the mRNA expression of MMP-13 and decreased the mRNA and protein
expression of TbetaRII, but these effects were diminished by SKP transplantation.
The transplantation of SKP could increase the mRNA of TIMP-1. CONCLUSIONS: We
found that transplanted SKP exert a beneficial impact on preventing UV-induced
wrinkles in vivo, suggesting that SKP transplantation is a promising candidate
for preventing photoaging.
PMID- 29943462
TI - Design of Silica-Oligourethane-Collagen Membranes for Inflammatory Response
Modulation: Characterization and Polarization of a Macrophage Cell Line.
AB - The polarization of macrophages M0 to M1 or M2 using molecules embedded in
matrices and hydrogels is an active field of study. The design of biomaterials
capable of promoting polarization has become a paramount need nowadays, since in
the healing process macrophages M1 and M2 modulate the inflammatory response. In
this work, several immunocytochemistry and ELISA tests strongly suggest the
achievement of polarization using collagen-based membranes crosslinked with tri
functionalized oligourethanes and coated with silica. Measuring the amount of TGF
beta1 secreted to culture media by macrophages growth on these materials, and
quantifying the macrophage morphology, it is proved that it is possible to
stimulate the anti-inflammatory pathway toward M2, having measurements with p <=
0.05 of statistical significance between the control and the collagen-based
membranes. Furthermore, some physicochemical characteristics of the hybrid
materials are tested envisaging future applications: collagenase degradation
resistance, water uptake, collagen fiber diameter, and deformation resistance are
increased for all the crosslinked biomaterials. It is considered that the
biological and physicochemical properties make the material suitable for the
modulation of the inflammatory response in the chronic wounds and promising for
in vivo studies.
PMID- 29943463
TI - Osteochondral resurfacing implantation angle is more important than implant
material stiffness.
AB - Osteochondral resurfacing implants are a promising treatment for focal cartilage
defects. Several implant-factors may affect the clinical outcome of this
treatment, such as the implant material stiffness and the accuracy of implant
placement, known to be challenging. In general, softer implants are expected to
be more accommodating for implant misalignment than stiffer implants, and motion
is expected to increase effects from implant misalignment and stiffness. 3D
finite element models of cartilage/cartilage contact were employed in which
implantation angle (0 degrees , 5 degrees , 10 degrees ) and implant material
stiffness (E = 5 MPa, 100 MPa, 2 GPa) were varied. A creep loading (0.6 MPa) was
simulated, followed by a sliding motion. Creep loading resulted in low maximum
collagen strains of 2.5% in the intact case compared to 11.7% with an empty
defect. Implants mostly positively affected collagen strains, deviatoric strains,
and hydrostatic pressures in the adjacent cartilage, but these effects were
superior for correct alignment (0 degrees ). The main effect of implant
misalignment was bulging of opposing cartilage tissue into the gap caused by the
misalignment. This increased collagen strains and hydrostatic pressures.
Deviatoric strains were increased adjacent to the gap. Subsequent sliding
initially increased strains for a stiff, misaligned implant, but generally
sliding decreased strains. In conclusion, implants can decrease the detrimental
effect of defects, but correct implant alignment is crucial, more than implant
material stiffness. Implant misalignment causes a gap, causing potentially
damaging cartilage deformation during prolonged loading, for example, standing,
even for soft implants. Mild motion may positively affect the cartilage. (c) 2018
The Authors. Journal of Orthopaedic Research(r) published by Wiley Periodicals,
Inc. on behalf of Orthopaedic Research Society. J Orthop Res 9999:1-12, 2018.
PMID- 29943464
TI - When I say ... sociocultural learning theory.
PMID- 29943465
TI - Improvement in dissolution rate and photodynamic efficacy of chlorin e6 by
sucrose esters as drug carrier in nanosuspension formulation: optimisation and in
vitro characterisation.
AB - OBJECTIVES: Chlorin e6 is a poorly water-soluble photoactive drug. Its monomers
form aggregates at the tumour physiological pH, which drastically reduces its
photodynamic efficacy. This study aimed to improve the dissolution rate and
photodynamic efficacy of chlorin e6 by nanosuspension formulation using
biodegradable sucrose esters as drug carrier. METHODS: A modified emulsion
solvent diffusion method was used to prepare the nanosuspension, where amount of
Ce6, ratio of sucrose monopalmitate to sucrose monolaurate as carrier and ratio
of dichloromethane to acetone as solvent, were varied using central composite
design. Particle size, zeta potential, encapsulation efficiency and in vitro drug
release characteristics of the nanosuspensions were evaluated. The formulation
was optimised by response surface methodology and its photodynamic efficacy
evaluated. KEY FINDINGS: The optimised nanosuspension had mean particle size of
~200 nm, 88% drug encapsulation efficiency and faster drug release compared to
pure Ce6. Spectroscopic studies showed that Ce6 exists in monomeric form in the
carrier, which facilitated a remarkable increase in cellular uptake, in vitro
singlet oxygen generation and cytotoxicity to oral squamous carcinoma cells.
CONCLUSIONS: The dissolution rate and photodynamic efficacy of Ce6 were markedly
improved by formulating the drug as a nanosuspension with sucrose esters as drug
carrier.
PMID- 29943466
TI - Semi-quantitative non-target analysis of water with liquid chromatography/high
resolution mass spectrometry: How far are we?
AB - Combining high-resolution mass spectrometry (HRMS) with liquid chromatography
(LC) has considerably increased the capability of analytical chemistry. Among
others, it has stimulated the growth of the non-target analysis, which aims at
identifying compounds without their preceding selection. This approach is already
widely applied in various fields, such as metabolomics, proteomics, etc. The
applicability of LC/HRMS-based non-target analysis in environmental analyses,
such as water studies, would be beneficial for understanding the environmental
fate of polar pollutants and evaluating the health risks exposed by the new
emerging contaminants. During the last five to seven years the use of LC/HRMS
based non-target analysis has grown rapidly. However, routine non-target analysis
is still uncommon for most environmental monitoring agencies and environmental
scientists. The main reasons are the complicated data processing and the
inability to provide quantitative information about identified compounds. The
latter shortcoming follows from the lack of standard substances, considered so
far as the soul of each quantitative analysis for the newly discovered
pollutants. To overcome this, non-target analyses could be combined with semi
quantitation. This Perspective aims at describing the current methods for non
target analysis, the possibilities and challenges of standard substance-free semi
quantitative analysis, and proposes tools to join these two fields together.
PMID- 29943467
TI - From ornament to armament or loss of function? Breeding plumage acquisition in a
genetically monogamous bird.
AB - The evolution of conspicuous male traits is thought to be driven by female mate
choice or male-male competition. These two mechanisms are often viewed as
distinct processes, with most studies focusing on female choice. However, both
mechanisms of sexual selection can act simultaneously on the same trait (i.e.,
dual function) and/or interact in a synergistic or conflicting way. Dual-function
traits are commonly assumed to originate through male-male competition before
being used in female choice; yet, most studies focusing on such traits could not
determine the direction of change, lacking phylogenetic information. We
investigated the role of conspicuous male seasonal plumage in male-male
competitive interactions in the purple-crowned fairy-wren Malurus coronatus, a
cooperatively breeding bird. Male breeding plumage in most Malurus species is
selected by female choice through extra-pair mate choice, but unlike its
congeners, M. coronatus is genetically monogamous, and females do not seem to
choose males based on breeding plumage acquisition. Our study shows that, within
groups, subordinate males that were older, and therefore higher-ranked in the
queue for breeder position inheritance, produced a more complete breeding
plumage. In line with this, subordinate males that were older and/or displayed a
more complete breeding plumage were more successful in competitively acquiring a
breeder position. A role as a signal of competitive ability was experimentally
confirmed by presenting models of males: in breeding colours, these received more
aggression from resident breeder males than in nonbreeding colours, but elicited
limited response from females, consistent with competitors in breeding plumage
being perceived as a bigger threat to the breeder male. The role of the
conspicuous breeding plumage in mediating male-male interactions might account
for its presence in this genetically monogamous species. As phylogenetic
reconstructions suggest a past female choice function in M. coronatus, this could
represent a sexual trait that shifted functions, or a dual-function trait that
lost one function. These evolutionary scenarios imply that intra- and intersexual
functions of ornaments may be gained or lost independently and offer new
perspectives in understanding the complex dynamics of sexual selection.
PMID- 29943469
TI - #SixSecondStudying: the rise and fall of Vine in MedEd.
PMID- 29943468
TI - Gastrointestinal: Colonic angiosarcoma in a patient initially presenting with leg
pain.
PMID- 29943470
TI - Pharmacokinetic/pharmacodynamic relationship of enrofloxacin against Aeromonas
hydrophila in crucian carp (Carassius auratus gibelio).
AB - The pharmacokinetic (PK) properties of enrofloxacin (ENR) and its metabolite
ciprofloxacin (CIP) were investigated in crucian carp following oral
administration at different dose levels (5, 10, 20, 40 mg/kg body weight). The
disposition kinetics of ENR was found to be linear over the dose range studied.
Serum half-lives ranged from 64.56 to 72.68 hr. The in vitro and ex vivo
activities of ENR in serum against a pathogenic strain of Aeromonas hydrophila
were determined. In vitro and ex vivo bactericidal activity of ENR was
concentration dependent. Dosing of 10 mg/kg resulted in an AUC/minimum inhibitory
concentration (MIC) ratio of 368.92 hr and a Cmax /MIC ratio of 7.23,
respectively, against A. hydrophila 147 (MIC = 0.48 MUg/ml), indicating a likely
high level of effectiveness in clinical infections caused by A. hydrophila with
MIC value <= 0.48 MUg/ml. Modeling of ex vivo growth inhibition data to the
sigmoid Emax equation provided the values of AUC24 hr /MIC required to produce
bacteriostasis, bactericidal activity, and elimination of bacteria, these values
were 21.70, 53.01, and 125.21 hr, respectively. These findings in conjunction
with MIC90 data suggested that ENR at the dose of 7.81 mg/kg predicted a positive
clinical outcome and minimize the risk of emergence of resistance.
PMID- 29943471
TI - MiR-126 correlates with increased disease severity and promotes keratinocytes
proliferation and inflammation while suppresses cells' apoptosis in psoriasis.
AB - BACKGROUND: This study aimed to investigate the miR-126 expression in lesional
skin and its correlation with clinical features in psoriasis patients and to
explore the effect of upregulated miR-126 on cells' proliferation, apoptosis, and
inflammation in human keratinocytes. METHODS: A total of 102 psoriasis patients
were consecutively enrolled in this study. MiR-126 expressions in lesional skin
and paired nonlesional skin were detected by quantitative polymerase chain
reaction (qPCR). Human keratinocytes (HaCaT cells) were transfected with miR-126
mimic plasmids and blank mimic plasmid. Cell Counting Kit-8 and annexin
V/propidium iodide assays were performed to assess the cells' proliferation and
apoptosis, and protein levels of apoptotic markers (cleaved caspase-3 [C-caspase
3] and B-cell lymphoma-2 [Bcl-2]) were detected by Western blot assay.
Inflammatory cytokines mRNA and protein levels were detected by qPCR and Western
blot assays, respectively. RESULTS: MiR-126 expression was upregulated in
lesional skin tissue compared with paired nonlesional skin tissue, and its
expression positively associated with Psoriasis Area and Severity Index score in
psoriasis patients. MiR-126 expression was increased in miR-126 mimic group
compared with negative control (NC) mimic group after plasmids transfection into
HaCaT cells, and cells' proliferation was enhanced while cells' apoptosis rate
was reduced in miR-126 mimic group than NC mimic group. Protein expressions of C
caspase and Bcl-2 also indicated miR-126 mimic decreased the cells' apoptosis. In
addition, miR-126 mimic increased TNF-alpha, IFN-gamma, IL-17A, and IL-22
expressions while decreased IL-10 expression. CONCLUSION: In conclusion, miR-126
correlates with elevated risk and increased disease severity in psoriasis
patients, and upregulation of miR-126 promotes cells' proliferation and
inflammation while inhibits cells' apoptosis in keratinocytes.
PMID- 29943472
TI - mHealth resources for asthma and pregnancy care: Methodological issues and social
media recruitment. A discussion paper.
AB - AIMS: A discussion of methodological issues and social media recruitment to a
feasibility study to investigate mHealth resources for asthma and pregnancy care.
BACKGROUND: Pregnant women with asthma are reported to be poorly supported
according to an international research. We sought to establish if a mHealth
intervention might be feasible and acceptable to them. DESIGN: A Phase I or
modelling study. METHODS: A project team designed an intervention to address UK
national guidelines for the management of asthma during pregnancy, using other
resources already accessible on the web. This was made available on a project
website optimized for mobile phone usage. Links were Tweeted and advertised on
Facebook, asking participants to access the project website, which included links
to the resources and before- and after-use questionnaires to establish baseline
symptom data and participant views of the resources. RESULTS: Despite 55,700
Twitter impressions in a 76-day period over winter 2016-2017, this recruitment
strategy garnered 402 engagements but only seven respondents for questionnaire 1
and zero respondents for questionnaire 2. CONCLUSIONS: We could not recruit to
this study despite believing that social media recruitment would be effective and
we recommend that social media recruitment be used cautiously. Apparently, we did
not sufficiently address the theoretical aspects of communications theory and
were not clear enough about our key messages. Publication bias may exist about
the non-publication of other failed telemedicine studies using social media; this
goes largely unreported in some systematic reviews and may influence researchers'
decision-making about social media recruitment.
PMID- 29943473
TI - Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in
Iran.
AB - T-cell receptor excision circles (TRECs) and kappa-deleting recombination
excision circles (KRECs) are recently used for detection of T or B cell
lymphopenia in neonates based on region-specific cutoff levels. Here, we report
cutoffs for TREC and KREC copies useful for newborn screening and/or diagnosis of
primary immunodeficiency diseases (PID) in Iran. DNA was extracted from a single
3.2 mm punch of dried blood spots collected from 2160 anonymized newborns
referred to two major referral health centers between 2014 and 2016. For
refinement of the cutoffs, 51 patients with a definite diagnosis of severe
combined immunodeficiency, X-linked agammaglobulinaemia and combined
immunodeficiency, including ataxia telangiectasia, human phosphoglucomutase 3 and
Janus kinase-3 deficiency, as well as 47 healthy controls were included. Samples
from patients with an X-linked hyper-IgM-syndrome, Wiskott-Aldrich syndrome and
DNA ligase 4 deficiency were considered as disease controls. Triplex-quantitative
real-time PCR was used. Cutoffs were calculated as TRECs < 11 and KRECs < 6
copies with an ACTB > 700 copies with sensitivity of 100% for TREC and 97% for
KREC. Among thirty anonymized newborn samples (1.5%) with abnormal results for
TREC and/or KREC, only twenty one available cases were retested and shown to be
in the normal range except for three samples (0.15%). All of the patients with a
definitive diagnosis were correctly identified based on our established TREC/KREC
copy numbers. Determining cutoffs for TREC/KREC is essential for correctly
identifying children with PID in newborn screening. Early diagnosis of PID
patients enables appropriate measures and therapies like stem cell
transplantation. This article is protected by copyright. All rights reserved.
PMID- 29943474
TI - Strategies for imputing missing covariates in accelerated failure time models.
AB - Missing covariates often occur in biomedical studies with survival outcomes.
Multiple imputation via chained equations (MICE) is a semi-parametric and
flexible approach that imputes multivariate data by a series of conditional
models, one for each incomplete variable. When applying MICE, practitioners tend
to specify the conditional models in a simple fashion largely dictated by the
software, which could lead to suboptimal results. Practical guidelines for
specifying appropriate conditional models in MICE are lacking. Motivated by a
study of time to hip fractures in the Women's Health Initiative Observational
Study using accelerated failure time models, we propose and experiment with some
rationales leading to appropriate MICE specifications. This strategy starts with
specifying a joint model for the variables involved. We first derive the
conditional distribution of each variable under the joint model, then approximate
these conditional distributions to the extent which can be characterized by
commonly used regression models. We propose to fit separate models to impute
incomplete variables by the failure status, which is key to generating
appropriate MICE specifications for survival outcomes. The proposed strategy can
be conveniently implemented with all available imputation software that uses
fully conditional specifications. Our simulation results show that some commonly
used simple MICE specifications can produce suboptimal results, while those based
on the proposed strategy appear to perform well and be robust toward model
misspecifications. Hence, we warn against a mechanical use of MICE and suggest
careful modeling of the conditional distributions of variables to ensure proper
performance.
PMID- 29943475
TI - Gas-phase stability of sandwich complexes of crown ethers with metal cations - as
studied by collision induced dissociation tandem mass spectrometry.
AB - RATIONALE: The gas-phase stabilities of the sandwich complexes formed by 12-crown
4 or 15-crown-5 with metal cations (Na+ , K+ , Rb+ , Tl+ , Ag+ , Ca2+ , Sr2+ ,
Ba2+ , Pb2+ , Hg2+ , Cd2+ ) are compared with the stability of the sandwich
complex formed by benzo-12-crown-4 or benzo-15-crown-5 with the cations. It is
interesting to check if the possible cation-pi interactions increase the gas
phase stabilities of the sandwich complexes of benzo-crown ethers with metal
cations. METHODS: The sandwich complexes were generated in the gas phase by
electrospray ionization (ESI) and then they were subjected to the collision
induced dissociation tandem mass spectrometry experiments (CID-MS/MS). On the
basis of the obtained product ion spectra, the respective breakdown plots of the
ion abundances ratios against collision energy expressed in the terms of center
of-mass were made. RESULTS: The gas-phase stabilities of [(B12C4)2 +Tl]+ ,
[(B15C5)2 +SrNO3 ]+ , [(B15C5)2 +PbNO3 ]+ and [(B15C5)2 +SrCl]+ were higher than
those of [(12C4)2 +Tl]+ , [(15C5)2 +SrNO3 ]+ , [(15C5)2 +PbNO3 ]+ and [(15C5)2
+SrCl]+ , respectively. For the other sandwich complexes the stabilities of the
complexes with benzo-crown ethers were not higher than those of the complexes of
simple crown ethers. CONCLUSIONS: It is reasonable to assume that the cation-pi
interaction increases the stability of the sandwich complex of B12C4 with Tl+ and
the stabilities of sandwich complexes of B15C5 with Sr2+ and Pb2+ .
PMID- 29943476
TI - Multi-drug ultraperformance liquid chromatography/tandem mass spectrometry method
to quantify antimicrobials in feeding stuffs at carry-over level.
AB - RATIONALE: Carry-over is an undesirable contamination from medicated to non
medicated during the production of feedingstuffs. In 2014 the European Parliament
and the Council started working to produce a new regulatory act that will fix
tolerable levels of drugs by carry-over in non-target feed to have a harmonized
practice to evaluate this contamination by veterinary drugs. METHODS: We
developed a rapid and effective multi-analyte method coupling ultraperformance
liquid chromatography to tandem mass spectrometry (UPLC/MS/MS) for the detection
of 37 drugs belonging to different classes of antimicrobials (sulfonamides,
tetracyclines, macrolides, quinolones, pleuromutilins and streptogramins) in
feeds at carry-over levels. The method was in-house validated in the
concentration range 0.25-2.0 mg kg-1 , according to the Regulation (UE) 2017/625
requirements and the guideline included in the Commission Decision 2002/657/EC
for official methods. RESULTS: The UPLC/MS/MS method allows the determination of
the antimicrobials in 15 min, by providing results compliant to the criteria
established by the European Commission legislation. All the analytes showed a
limit of detection (LOD) in the range 2.0-5.0 MUg kg-1 and a limit of
quantification (LOQ) at 10.0 MUg kg-1 ; oxytetracycline, doxycycline, spiramycin
and virginiamycin have a higher LOD and LOQ (15.0 MUg kg-1 ; 30.0 MUg kg-1 ,
respectively). Recoveries were satisfactory ranging from 90.4% to 103.1%.
CONCLUSIONS: The method is characterized by an effective clean-up of all drugs
without the use of large sample size and organic solvent extraction.
PMID- 29943477
TI - Length-based body weight estimation in paediatric patients: The impact of habitus
A clinical observational trial.
AB - BACKGROUND: Paediatric emergency tapes provide drug dosing based on the patient's
estimated body weight. Unfortunately, published data revealed an unsatisfactory
accuracy. A newly developed digital algorithm for weight estimation (CLAWAR)
allowing a three-staged habitus adaptation (normal, obese, or cachectic; CLAWAR
3) demonstrated a higher accuracy for weight estimation compared to paediatric
emergency tapes. However, the incidence of incorrectly evaluated habitus was 27%.
A five-staged habitus adaptation with figural images was suggested by Wells et al
to improve habitus and weight estimation. Therefore, CLAWAR was modified with
five habitus stages including figural images (CLAWAR-5). We hypothized CLAWAR-5
improves the accuracy of weight estimation. METHODS: After obtaining informed
written parental consent patients were included in this single centre,
prospective clinical observation trial. Body weight estimations by CLAWAR-3 and
CLAWAR-5 within +/-10% of the actual body weight were compared. Furthermore, the
incidence of correct evaluated habitus was calculated. McNemar Tests were used
for statistical analysis. Results presented as median (interquartiles), P < .003
considered significant. RESULTS: In total, 312 patients aged 3.3 years (0.7-6.6),
with a body length of 95.9 cm (70.0-121.2), weighing 14.8 kg (8.1-22.5), were
included. Both CLAWAR-3 and CLAWAR-5 showed equivalent accuracy for weight
estimation within the +/-10% interval (62.2% vs 60.6%, P = .609). Despite adding
figural images, the incidence of correct evaluated habitus with CLAWAR-5 (46.8%)
was worse than with CLAWAR-3 (66.7%). CONCLUSION: The five-staged habitus-adapted
method could not improve the accuracy of weight estimation. Furthermore, the
error rate of habitus classification was not reduced by the implementation of
figural images.
PMID- 29943478
TI - Reciprocal link between cell biomechanics and exocytosis.
AB - A cell is able to sense the biomechanical properties of the environment such as
the rigidity of the extracellular matrix and adapt its tension via regulation of
plasma membrane and underlying actomyosin meshwork properties. The cell's ability
to adapt to the changing biomechanical environment is important for cellular
homeostasis and also cell dynamics such as cell growth and motility. Membrane
trafficking has emerged as an important mechanism to regulate cell biomechanics.
In this review, we summarize the current understanding of the role of cell
mechanics in exocytosis, and reciprocally, the role of exocytosis in regulating
cell mechanics. We also discuss how cell mechanics and membrane trafficking,
particularly exocytosis, can work together to regulate cell polarity and
motility.
PMID- 29943479
TI - The main beneficial effect of roselle (Hibiscus sabdariffa) on obesity is not
only related to its anthocyanin content.
AB - BACKGROUND: The calyxes of roselle (Hibiscus sabdariffa) are recognized for their
high nutraceutical value because they decrease body weight and obesity
complications. These effects have been attributed mainly to anthocyanins.
However, the calyxes comprise important concentration of flavonoids, phenolic,
and organic acids, which could also contribute to these effects. The objective of
this work was to determine the effect of the Alma Blanca white roselle variety on
obesity and hepatic steatosis in high-fat, high-fructose, diet-fed rats and
compare its beneficial effects with the red variety (Criolla), which has been
more extensively studied. RESULTS: Aqueous and methanolic extracts were prepared
from two roselle varieties, Alma Blanca (white) and Criolla (red). The
phytochemical profiles were determined using high-performance liquid
chromatography-mass spectrometry (HPLC-MS). Criolla extracts contain principally
anthocyanins, phenolic acids, and flavonoids. Anthocyanins were not detected in
Alma Blanca. The aqueous extracts of both varieties prevented body-weight gain
and decreased adipocytes hyperplasia on rats fed a hypercaloric diet. These
extracts also protected against hepatic steatosis. These benefits were associated
with hibiscus, dimethyl hibiscus, and hydroxycitric acid. CONCLUSION: These
results demonstrated that calyxes from Hibiscus sabdariffa contain compounds that
are different from anthocyanins, with potential benefits to health. The organic
acids were strongly associated with these beneficial health effects. (c) 2018
Society of Chemical Industry.
PMID- 29943480
TI - High frequency of variant RHD genotypes among donors and patients of mixed origin
with serologic weak-D phenotype.
AB - BACKGROUND: The current transfusion policy recommended for individuals with
serologic weak-D phenotype is based on data derived from European-descent
populations. Data referring to the distribution of RH alleles underlying weak-D
phenotype among people of mixed origin are yet incomplete, and the applicability
of European-based transfusion guidelines to this specific population is
questionable. GOAL: To evaluate the distribution of RHD variant genotype among
individuals with serologic weak-D phenotype of both African and European descent.
METHODS: Donors and patients of mixed origin and with serologic weak-D phenotype
were selected for the study. They were investigated using conventional RHD-PCR
assays and RHD whole-coding region direct sequencing. RESULTS: One hundred and
six donors and 58 patients were included. There were 47 donors and 29 patients
with partial-D genotype (47/106, 44.3%, and 29/58, 50%, respectively). RHD*DAR
and RHD*weak D type 38 represented the most common altered RHD alleles among
donors (joint frequency of 39.6%), while weak D types 1-3 accounted for 10.4% of
the total D variant samples. RHD*DAR was the most common allele identified in the
patient group (frequency of 31%), and weak D types 1-3 represented 29.3% of the
total. CONCLUSION: The frequency of partial D among mixed individuals with
serologic weak-D phenotype is high. They should be managed as D-negative patients
until molecular tests are complete.
PMID- 29943481
TI - Using vignettes to understand heart failure self-care.
AB - AIMS AND OBJECTIVES: To explore hospitalised heart failure (HF) patients' self
care decisions. BACKGROUND: Heart failure self-care is integral to maintain and
manage health, and may prevent unnecessary HF hospitalisations. Nevertheless,
self-care remains challenging for patients, and using vignettes offer a new
perspective to understand patient HF self-care decision-making. DESIGN: This
qualitative descriptive analysis was conducted as part of a mixed methods study.
METHODS: We conducted semi-structured interviews (N = 20) to elicit patient
decisions about self-care in responses to three vignettes, which varied in
symptom severity. Content analysis was used to extract quotes describing
participant responses. RESULTS: Participants were on average 60 years old,
primarily male, African American, unemployed and highly symptomatic (NYHA Class
III or IV). Overall, participants were able to identify when symptoms required a
decision to seek urgent medical attention, but had difficulty identifying the
appropriate decision to make in response to less acute symptoms such as swelling.
CONCLUSIONS: Symptoms other than shortness of breath were challenging for
patients to interpret and manage appropriately. Understanding how to apply HF
knowledge to alleviate symptoms was also difficult. RELEVANCE TO CLINICAL
PRACTICE: Vignettes may be a helpful tool to prompt patient-healthcare provider
communication about self-care management and prompt discussions about appropriate
self-care decisions in response to varying levels of symptom severity.
PMID- 29943482
TI - Effects of Electrolyte Anions on the Reduction of Carbon Dioxide to Ethylene and
Ethanol on Copper (100) and (111) Surfaces.
AB - The CO2 electroreduction reaction has been investigated on Cu(100) and Cu(111)
surfaces in 0.1 m aqueous solutions of KClO4 , KCl, KBr, and KI electrolyte. The
formation of ethylene and ethanol on these surfaces generally increased as the
electrolyte anion was changed from ClO4- ->Cl- ->Br- ->I- . For example, on
Cu(100) at -1.23 V versus RHE, as the electrolyte anion changed from ClO4- to I-
, the faradaic efficiency (FE) of ethylene formation increased from 31 to 50 %,
FEethanol increased from 7 to 16 %, and the associated current densities
increased five- and sevenfold, respectively. A remarkable total FE of up to 74 %
for C2 and C3 products was obtained in the presence of KI. Despite surface
roughening in the presence of the electrolytes, the Cu(100) electrode still
enhanced the formation of C2 compounds better than Cu(111). The favorable
reduction of CO2 to C2 products in KI electrolyte was correlated with a higher
*CO population on the surface, as shown using linear sweep voltammetry. In situ
Raman spectroscopy indicated that the coordination environment of *CO was altered
by the used electrolyte anion. Thus, apart from affecting the morphology of the
electrode and local pH value, we propose that the anion plays a critical role in
enhancing the formation of C2 products by tuning the coordination environment of
adsorbed *CO, which gives rise to more efficient C-C coupling.
PMID- 29943483
TI - Impact of preoperative biliary drainage on postoperative outcome after
pancreaticoduodenectomy: An analysis of 1500 consecutive cases.
AB - BACKGROUND AND AIM: Implications of preoperative biliary drain on morbidity and
mortality after pancreatoduodenectomy are still controversial. The present study
aims to assess the impact of preoperative biliary drain on postoperative outcome
and to define optimal serum bilirubin cut-off to recommend biliary drainage in
patients undergoing pancreatoduodenectomy. METHODS: All consecutive
pancreatoduodenectomies carried out at Verona Hospital from 2005 to 2016 were
retrospectively analyzed. The study population was divided into three groups:
preoperative biliary drained (Stented Group), preoperative jaundice without
drainage (Jaundiced Group) and the control group of non-jaundiced, non-stented
patients (Control Group). RESULTS: A total of 1500 patients were included. Seven
hundred and fourteen patients (47.6%) received biliary drain (stented group), 258
(17.2%) patients did not (jaundiced group) and 528 (35.2%) patients represented
the (control group). Major complications and mortality rates did not differ
between groups. Conversely, the risk of developing surgical site infections
doubled in the stented group (18.1%) (OR = 2.1, 95% CI = 1.5-2.8). In jaundiced
patients, a preoperative bilirubin value greater than 7.5 mg/dL (128 MUmol/L)
accurately predicted the likelihood of postoperative complications. CONCLUSION:
Preoperative biliary drain does not increase major complications and mortality
rates after pancreatoduodenectomy, but it is associated with higher surgical site
infection rates. In jaundiced patients, a bilirubin value greater than 7.5 mg/dL
(128 MUmol/L) should indicate biliary drainage.
PMID- 29943486
TI - Effectiveness of interprofessional education and new prospects.
PMID- 29943484
TI - Differential aging-related changes in neurophysiology and gene expression in IB4
positive and IB4-negative nociceptive neurons.
AB - Despite pain prevalence altering with age, the effects of aging on the properties
of nociceptors are not well understood. Nociceptors, whose somas are located in
dorsal root ganglia, are frequently divided into two groups based on their
ability to bind isolectin B4 (IB4). Here, using cultured neurons from 1-, 3-, 5-,
8-, 12-, and 18-month-old mice, we investigate age-dependent changes in IB4
positive and IB4-negative neurons. Current-clamp experiments at physiological
temperature revealed nonlinear changes in firing frequency of IB4-positive, but
not IB4-negative neurons, with a peak at 8 months. This was likely due to the
presence of proexcitatory conductances activated at depolarized membrane
potentials and significantly higher input resistances found in IB4-positive
neurons from 8-month-old mice. Repetitive firing in nociceptors is driven
primarily by the TTX-resistant sodium current, and indeed, IB4-positive neurons
from 8-month-old mice were found to receive larger contributions from the TTX
resistant window current around the resting membrane potential. To further
address the mechanisms behind these differences, we performed RNA-seq experiments
on IB4-positive and IB4-negative neurons from 1-, 8-, and 18-month-old mice. We
found a larger number of genes significantly affected by age within the IB4
positive than IB4-negative neurons from 8-month-old mice, including known
determinants of nociceptor excitability. The above pronounced age-dependent
changes at the cellular and molecular levels in IB4-positive neurons point to
potential mechanisms behind the reported increase in pain sensitivity in middle
aged rodents and humans, and highlight the possibility of targeting a particular
group of neurons in the development of age-tailored pain treatments.
PMID- 29943485
TI - Study on the interaction of antidiabetic drug Pioglitazone with calf thymus DNA
using spectroscopic techniques.
AB - Pioglitazone is an antidiabetic drug used to treat type 2 diabetes mellitus.
Interaction of Pioglitazone with calf thymus DNA was investigated using
multispectroscopic techniques and molecular docking study. Quenching and binding
constant was calculated at 3 different temperatures. The binding constant of
Pioglitazone with calf thymus DNA was calculated to be 6.49 * 103 M-1 at 293 K.
The quenching mechanism was found to be a static process, and thermodynamic
parameters revealed van der Waals interactions and hydrogen bonds to be the major
force working in Pioglitazone-DNA interaction. Pioglitazone follows the
nonintercalative mode of binding and was involved in complex formation with DNA
through minor groove binding and electrostatic interactions. Experiments like KI
quenching studies, dye displacement assays, Circular Dichroism (CD) spectroscopy,
DNA melting study, and viscosity measurements studies supported the
nonintercalative mode of binding. This was further corroborated by molecular
docking studies.
PMID- 29943487
TI - Influence of reaction conditions on the oxidation of thiol groups in model
peptidomimetic oligoureas.
AB - Working with thiols is associated with the risk of unwanted oxidation reactions,
which includes the formation of disulfides. Here, the use of short peptidomimetic
oligoureas as a model system to study the influence of reaction conditions on the
thiol oxidation process is described. The formation of disulfide bond is usually
performed in aqueous solutions; in this study, it was shown that the oxidation
reaction occurs also in organic medium. It was discovered that the rate of the
oxidation reaction strongly depends on the type of solvent, which is the
consequence of the change of the oxidant (air or DMSO), the temperature, and the
presence (or absence) of base. The details reported here may help those working
with thiols to find suitable conditions to control the oxidation behaviour in
organic solvents, ensuring that ?SH groups either remain intact or form disulfide
bonds as desired.
PMID- 29943488
TI - Abscisic acid, cold and salt stimulate conserved metabolic regulation in the moss
Physcomitrella patens.
AB - Salt and cold are major abiotic stresses that have adverse effects on plant
growth and development. To cope with these stresses and their detrimental effects
plants have evolved several metabolic, biochemical and physiological processes
that are mainly triggered and mediated by the plant hormone abscisic acid (ABA).
To elucidate the metabolic responses of the moss Physcomitrella patens, which
serves as a model plant for abiotic stress adaptation, we performed GC-MS-based
metabolic profiling of plants challenged for 5 and 28 h with either salt, cold or
ABA. Our results indicate significant changes in the accumulation of several
sugars including maltose, isomaltose and trehalose, amino acids including
arginine, histidine, ornithine, tryptophan and tyrosine, and organic acids mainly
citric acid and malonic acid. The metabolic responses provoked by ABA, cold and
salt show considerable similarities. The accumulation of certain metabolites
positively correlates with gene expression data whereas some metabolites do not
show correlation with cognate transcript abundance. To place our results into an
evolutionary context we compared the ABA- and stress-induced metabolic changes in
moss to available metabolic profiles of the seed plant Arabidopsis thaliana. We
detected considerable conservation between the species, indicating early
evolution of stress-associated metabolic adaptations that probably occurred at
the plant water-to-land transition.
PMID- 29943489
TI - Metformin is associated with a lower risk of active tuberculosis in patients with
type 2 diabetes.
AB - BACKGROUND AND OBJECTIVE: Metformin is an oral anti-diabetic therapy (ADT) to
manage type 2 diabetes mellitus (T2DM), and has been reported to have potential
anti-tuberculosis (TB) effects. This study investigates the risk of active TB
among persons with T2DM who were treated with various ADT and insulin therapies.
METHODS: We conducted a nationwide population-based cohort study using the Taiwan
Longitudinal Health Insurance Database, including 49 028 T2DM patients who were
metformin users (n = 44 002) or non-users (n = 5026). A total of 5026 propensity
score-matched pairs of metformin users and non-users with T2DM were evaluated
from 1998 to 2010. The data were analysed using Cox proportional hazard models.
RESULTS: Patients with T2DM had a significantly higher rate of incident TB than
did the control subjects (adjusted hazard ratio: 2.01; 95% confidence interval
(95% CI): 1.80-2.25). After adjusting for comorbidities, diabetes complications,
ADT type and statin use, metformin use was an independent factor for predicting a
reduced risk of active TB (adjusted relative risk (aRR): 0.24; 95% CI: 0.18
0.32). The association between metformin use and active TB risk was also
consistent in most subgroup analyses, except for patients with metabolic
disorders (aRR: 0.46; 95% CI: 0.11-1.87). This protective effect of metformin was
dose-dependent but diminished gradually in the elderly population. CONCLUSION:
Among all types of ADT and insulin therapies, metformin is the only agent with a
decreased risk of active TB in the T2DM population. However, this effect was
diminished in the elderly population and was not observed in patients with
metabolic disorders.
PMID- 29943490
TI - Co-administrating apigenin in a high-cholesterol diet prevents
hypercholesterolaemia in golden hamsters.
AB - OBJECTIVES: Hypercholesterolaemia is a major risk factor for developing
atherosclerosis. Increased consumption of fruits and vegetables is recommended to
hypercholesterolaemic patients. In this study, the hypocholesterolaemic effect of
apigenin and luteolin was evaluated in a hamster model. METHODS: Hamsters were
put on a high-cholesterol diet for 9 weeks, and apigenin or luteolin was
administered in the diet at 60 and 300 ppm. KEY FINDINGS: Both apigenin and
luteolin supplementations could attenuate the aorta plaque formation by 30% and
20%, respectively. Apigenin-fed hamsters at both dosages displayed a 1.5-fold
increase in hepatic Ldlr expression and a 40% reduction in non-HDL cholesterol
level as compared with those in the control fed a high-cholesterol (HC) diet.
Besides, faecal elimination of cholesterol was facilitated by 20% in the hamsters
with high apigenin consumption. Suppressing the expression of the cholesterol
transporter ncp1l1 in the intestinal mucosa could block the cholesterol
absorption and promote its elimination. The differential regulations of ncp1l1
and Ldlr appeared to be the underlying hypocholesterolaemic mechanism of apigenin
in this model system. Luteolin supplementation, on the other hand, had no effect
on the blood cholesterol. CONCLUSIONS: This study illustrated that dietary
administration of apigenin attenuated HC feeding-induced hypercholesterolemia in
hamsters.
PMID- 29943491
TI - Relationship of demoralization with anxiety, depression, and quality of life: A
Southern European study of Italian and Portuguese cancer patients.
AB - BACKGROUND: Demoralization syndrome is a significant condition that has not been
greatly studied in Southern European countries. AIMS: To extend the knowledge of
demoralization in Southern Europe by examining its prevalence according to
different methods of assessment, its relationship with anxiety and depression,
and its impact on quality of life (QoL) among cancer patients. METHODS: A
convenience sample of 195 cancer outpatients from two oncology centers (102 from
Lisbon, Portugal, and 93 from Ferrara, Italy) participated in an observational,
cross-sectional study using the Diagnostic Criteria of Psychosomatic Research
Demoralization interview (DCPR/D) and psychometric tools (Demoralization scale
DS; Patient Health Questionnaire-9/PHQ-9; Hospital Anxiety Depression Scale-HADS;
and European Quality of Life-5-EQ-5D). RESULTS: A 25.1% prevalence (CI 95%, 0.19
0.31) of clinically relevant demoralization was reported on the DCPR/D interview.
A total demoralization score cutoff score >= 25 maximized sensitivity (81.6%),
and specificity (72.6%) in identifying DCPR/D demoralized patients. The DCPR/D
and DS were associated with poorer levels of QoL. About half of the patients who
were demoralized were not clinically depressed (PHQ-9). Self-reported suicidal
ideation (PHQ-9 item 9) was found in a minority of patients (8.2%), most of whom
(77%) were cases of depression (PHQ-9), but one-quarter (23%) were not depressed,
yet moderately/severely demoralized (DCPR/D and DS). CONCLUSIONS: This Southern
European study confirms the importance of demoralization in cancer patients as a
different condition with respect to depression and its relationship with poor QoL
and suicidal ideation.
PMID- 29943492
TI - Characteristic and influencing factors of Taqman genotyping calling error.
AB - BACKGROUND: Taqman fluorescent probe was frequently applied in single nucleotide
polymorphism (SNP) genotyping. However, the characteristic of calling error and
the influencing factors remain unclear. METHOD: Calling errors of Taqman
genotyping was evaluated systematically based on Mendelian inheritance. Twenty
two SNPs were genotyped by Taqman probe for 419 pedigrees. Mendelian genetic
errors were counted for every SNP and pedigree. Cluster analysis was applied to
investigate the compatibility between Taqman probes and DNA sample. RESULTS: On
one hand, errors were found for all the SNPs. The error number ranged from 4 to
33 with median of 10.5. On the other hand, Mendelian genetic errors showed
features of both randomness and cluster. Half of the pedigrees containing errors
had only 1 Mendelian genetic error. But there was also a pedigree containing up
to 10 Mendelian genetic errors. Furthermore, cluster analysis indicated that
errors of different SNPs took place in different pedigree cluster. CONCLUSION: It
could be concluded that calling error is inevitable for Taqman genotyping of
large samples. The quality of Taqman probe and DNA sample, as well as their
compatibility, may account for the error incidence.
PMID- 29943493
TI - Hypoglycaemia risk in the first 8 weeks of titration with insulin glargine 100
U/mL in previously insulin-naive individuals with type 2 diabetes mellitus.
AB - Patient characteristics associated with hypoglycaemia frequency during insulin
glargine 100 U/mL (Gla-100) titration and clinical outcomes at Week 24 were
examined using participant-level data from 16 treat-to-target trials involving
individuals with type 2 diabetes mellitus who were inadequately controlled with
oral antidiabetes drugs and were initiating Gla-100 (n = 3549). Hypoglycaemia
(plasma glucose <3.9 mmol/L or severe) during the first 8 weeks of titration was
stratified by number of events (0, 1-3 and >=4), resulting in 72.5%, 20.6% and
6.9% of participants in each group, respectively. Changes in glycaemia, body
weight and insulin dose from baseline to Weeks 12 and 24 were analysed.
Hypoglycaemia was more common in participants with lower BMI and fasting C
peptide, and in those undergoing sulfonylurea treatment. Glycaemic outcomes at
Week 24 were similar in each hypoglycaemia group, despite the fact that the Week
24 mean daily dose and dose increase for Gla-100 were highest in participants
without hypoglycaemia and were lowest in those experiencing >=4 events. The risk
of hypoglycaemia during Gla-100 titration depends mainly on patient
characteristics and on sulfonylurea use and may delay dose titration, which
apparently has little effect on short-term glycaemic control in a clinical trial
setting.
PMID- 29943494
TI - MART-1-labeled melanocyte density and distribution in actinic keratosis and
squamous cell cancer in situ: Pagetoid melanocytes are a potential source of
misdiagnosis as melanoma in situ.
AB - BACKGROUND: Actinic keratosis (AK) and squamous cell carcinoma in-situ (SCCIS)
within or near melanoma in situ (MIS) can complicate diagnosis due to overlapping
clinical and microscopic features. This study aimed to describe basilar
melanocyte density and pagetoid spread in AK and SCCIS for improved diagnostic
accuracy. METHODS: A total of 22 AK and 22 SCCIS biopsies containing a margin of
uninvolved epidermis were immunostained with MART-1 (melanoma antigen recognized
by T-cells 1). The basilar melanocyte:keratinocyte ratio and the number and
distribution of pagetoid melanocytes were compared in AK, SCCIS, and uninvolved
epidermis. An in-vitro human skin model was created to assess the impact of
keratinocyte atypia on melanocyte distribution. RESULTS: The median basilar
melanocyte:keratinocyte ratio in SCCIS (1:11.49) was lower than in uninvolved
epidermis (1:5.59, P = 0.0011), and the ratio in AK (1:6.94) was similar to
uninvolved epidermis (P = 0.987). Pagetoid melanocytes were absent in
perilesional skin but common in AK (21/22, P < 0.0001) and SCCIS (22/22, P <
0.0001). Pagetoid melanocytes at or above the mid-spinous layer were more common
in SCCIS (21/22) vs AK (7/22, P < 0.0001). Pagetoid melanocytes were present in
the in-vitro skin model made with neoplastic but not normal keratinocytes.
CONCLUSIONS: Pagetoid melanocytes in AK and SCCIS should be interpreted with
caution to avoid overdiagnosis of MIS.
PMID- 29943495
TI - Triflimide: An Overlooked High-Performance Catalyst of the Mukaiyama Aldol
Reaction of Silyl Ketene Acetals with Ketones.
AB - The Mukaiyama aldol reaction is a widely applied carbon-carbon bond forming
reaction. However, despite numerous well-established methods using aldehydes as
acceptors, only few examples exist with ketones. Here we report a highly
practical catalytic approach to this transformation, namely, the triflimide
catalyzed Mukaiyama aldol reaction of silyl ketene acetals with ketones. This
method exhibits a broad substrate scope, is very rapid, tolerates functionalized
substrates, and requires only parts-per-million catalyst loadings with
preparative scale reactions up to hundreds of grams in excellent purity (>99 %).
PMID- 29943496
TI - Role of dietary amino acid balance in diet restriction-mediated lifespan
extension, renoprotection, and muscle weakness in aged mice.
AB - Extending healthy lifespan is an emerging issue in an aging society. This study
was designed to identify a dietary method of extending lifespan, promoting
renoprotection, and preventing muscle weakness in aged mice, with a focus on the
importance of the balance between dietary essential (EAAs) and nonessential amino
acids (NEAAs) on the dietary restriction (DR)-induced antiaging effect. Groups of
aged mice were fed ad libitum, a simple DR, or a DR with recovering NEAAs or
EAAs. Simple DR significantly extended lifespan and ameliorated age-related
kidney injury; however, the beneficial effects of DR were canceled by recovering
dietary EAA but not NEAA. Simple DR prevented the age-dependent decrease in slow
twitch muscle fiber function but reduced absolute fast-twitch muscle fiber
function. DR-induced fast-twitch muscle fiber dysfunction was improved by
recovering either dietary NEAAs or EAAs. In the ad libitum-fed and the DR plus
EAA groups, the renal content of methionine, an EAA, was significantly higher,
accompanied by lower renal production of hydrogen sulfide (H2 S), an endogenous
antioxidant. Finally, removal of methionine from the dietary EAA supplement
diminished the adverse effects of dietary EAA on lifespan and kidney injury in
the diet-restricted aged mice, which were accompanied by a recovery in H2 S
production capacity and lower oxidative stress. These data imply that a dietary
approach could combat kidney aging and prolong lifespan, while preventing muscle
weakness, and suggest that renal methionine metabolism and the trans-sulfuration
pathway could be therapeutic targets for preventing kidney aging and subsequently
promoting healthy aging.
PMID- 29943497
TI - Increased exhausted CD8+ T cells with programmed death-1, T-cell immunoglobulin
and mucin-domain-containing-3 phenotype in patients with multiple myeloma.
AB - AIM: The immunosuppressive microenvironment plays a crucial role in T-cell
immunodeficiency in multiple myeloma (MM). Overexpression of T-cell
immunosuppressive receptors, including programmed death-1 (PD-1) and T-cell
immunoglobulin and mucin-domain-containing-3 (Tim-3), may be related to tumor
immunosuppression and poor prognosis, and the malignant bone marrow (BM)
microenvironment may contribute to such immunosuppression. The purpose of this
study was to analyze the distribution of PD-1+ and/or Tim-3+ T cells in different
T-cell subset in patients with MM. METHODS: The expression of PD-1 and Tim-3 with
exhausted (CD244+ and CD57+ ) CD3+ , CD4+ and CD8+ T cells between BM and
peripheral blood (PB) from 10 patients with untreated MM was detected by
multicolor flow cytometry assay. RESULTS: A significant increase in both PD-1+
CD57+ and Tim-3+ CD57+ CD3+ T cells and PD-1+ Tim-3+ CD3+ T cells was detected in
PB from patients with MM compared with 10 healthy individuals (HIs), and the
alteration was mostly in the CD8+ T-cell subset. Significant higher percentage of
PD-1+ CD3+ T cells was found in BM compared with PB from patients with MM. The
level of PD-1+ Tim-3+ CD3+ , CD4+ , and CD8+ T cells was high in BM group
compared with PB. Moreover, PD-1+ CD244+ or PD-1+ CD57+ CD3+ T cells,
particularly PD-1+ CD244+ and PD-1+ CD57+ CD8+ T cells were significantly higher
in BM than in PB. In addition, limited dynamic detection data from three MM cases
who achieved complete remission after treatment showed that the numbers of either
PD-1+ or PD-1+ Tim-3+ T cells in different T-cell subsets were decreased in both
BM and PB. CONCLUSION: We characterized the distribution of PD-1 and TIM-3
concurrent with exhausted CD3+ , CD4+ and CD8+ T cells between BM and PB from
patients with MM. Higher numbers of PD-1+ CD244+ or PD-1+ CD57+ CD3+ T cells in
BM from patients with MM may contribute to mediate the BM immunosuppressive
microenvironment. Although heterogeneous alterations in Tim-3+ T cells may
represent a complex immunosuppressive pattern in MM. Overall, higher levels of PD
1+ CD244+ or PD-1/Tim-3+ CD57+ CD8+ T cells may be a major reason for lower T
cell activation and T-cell immunodeficiency in MM.
PMID- 29943498
TI - Management of pregnancies after combined screening for pre-eclampsia at 19-24
weeks' gestation.
AB - OBJECTIVE: To estimate the patient-specific risk of pre-eclampsia (PE) at 19-24
weeks' gestation by maternal factors and combinations of mean arterial pressure
(MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor
(PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). On the basis of the
risk of PE, the women would be stratified into high-, intermediate- and low-risk
management groups. The high-risk group would require close monitoring for high
blood pressure and proteinuria at 24-31 weeks. The intermediate-risk group,
together with the undelivered pregnancies from the high-risk group, would have
reassessment of risk for PE at 32 weeks to identify those who would require close
monitoring for high blood pressure and proteinuria at 32-35 weeks. All
pregnancies would have reassessment of risk for PE at 36 weeks to define the plan
for further monitoring and delivery. METHODS: This was a prospective
observational study of women attending for an ultrasound scan at 19-24 weeks as
part of routine pregnancy care. Patient-specific risks of delivery with PE at <
32 and at < 36 weeks' gestation were calculated using the competing-risks model
to combine the prior distribution of gestational age at delivery with PE,
obtained from maternal characteristics and medical history, with multiples of the
median (MoM) values of MAP, UtA-PI, PlGF and sFlt-1. Different risk cut-offs were
used to vary the proportion of the population stratified into high-, intermediate
and low-risk groups, and the performance of screening for delivery with PE at <
32 weeks' gestation and at 32 + 0 to 35 + 6 weeks was estimated. RESULTS: The
study population of 16 254 singleton pregnancies included 467 (2.9%) that
subsequently developed PE (23 delivered at < 32 weeks, 58 delivered at 32 + 0 to
35 + 6 weeks and 386 delivered at >= 36 weeks). Using a risk of > 1 in 25 for PE
at < 32 weeks' gestation and risk of > 1 in 150 for PE at < 36 weeks, the
proportion of the population stratified into the high-risk group was about 1% of
the total, and the proportion of cases of PE at < 32 weeks' gestation contained
within this high-risk group varied from about 35% with screening by maternal
factors and MAP, to 78% with maternal factors, MAP and UtA-PI, and up to 100%
with maternal factors, MAP, UtA-PI and PlGF, with or without sFlt-1. Similarly,
the proportion of the population requiring reassessment of risk at 32 weeks'
gestation and the proportion of cases of PE at 32 + 0 to 35 + 6 weeks contained
within this population varied, respectively, from about 18% and 79% with
screening by maternal factors and MAP, to 10% and 90% with maternal factors, MAP,
UtA-PI and PlGF, with or without sFlt-1. CONCLUSION: In the new pyramid of
pregnancy care, assessment of risk for PE at 19-24 weeks' gestation can stratify
the population into those requiring intensive monitoring at 24-31 weeks and those
in need of reassessment at 32 weeks. Copyright (c) 2018 ISUOG. Published by John
Wiley & Sons Ltd.
PMID- 29943499
TI - A General Strategy for Extrusion Bioprinting of Bio-Macromolecular Bioinks
through Alginate-Templated Dual-Stage Crosslinking.
AB - The recently developed 3D bioprinting technology has greatly improved the ability
to generate biomimetic tissues that are structurally and functionally relevant to
their human counterparts. The selection of proper biomaterials as the bioinks is
a key step toward successful bioprinting. For example, viscosity of a bioink is
an important rheological parameter to determine the flexibility in deposition of
free-standing structures and the maintenance of architectural integrity following
bioprinting. This requirement, however, has greatly limited the selection of
bioinks, especially for those naturally derived due to their commonly low
mechanical properties. Here the generalization of a mechanism for extrusion
bioprinting of bio-macromolecular components, mainly focusing on collagen and its
derivatives including gelatin and gelatin methacryloyl, is reported.
Specifically, a templating strategy is adopted using a composite bioink
containing both the desired bio-macromolecular component and a polysaccharide
alginate. The physically crosslinkable alginate component serves as the temporal
structural support to stabilize the shape of the construct during bioprinting;
upon subsequent chemical or physical crosslinking of the bio-macromolecular
component, alginate can be selectively removed to leave only the desired bio
macromolecule. It is anticipated that this strategy is general, and can be
readily expanded for use of a wide variety of other bio-macromolecular bioinks.
PMID- 29943500
TI - Activating KIR Haplotype Influences Clinical Outcome Following HLA-Matched
Sibling Hematopoietic Stem Cell Transplantation.
AB - Natural killer cells are thought to influence the outcome of hematopoietic stem
cell transplant (HSCT), impacting on relapse, overall survival, graft versus host
disease and the control of infection, in part through the complex interplay
between the large and genetically diverse killer immunoglobulin-like receptor
(KIR) family and their ligands. This study examined the relationship between KIR
gene content and clinical outcomes including the control of opportunistic
infections such as cytomegalovirus in the setting of human leucocyte antigen
(HLA)-matched sibling HSCT in an Australian cohort. The presence of the KIR B
haplotype which contain more activating receptors in the donor, in particular
centromeric B haplotype genes (Cen-B), was associated with improved overall
survival of patients with acute myeloid leukemia (AML) undergoing sibling HSCT
and receiving myeloablative conditioning. Donor Cen-B haplotype was also
associated with reduced acute graft versus host disease grades II-IV whereas
donor telomeric-B haplotype was associated with decreased incidence of CMV
reactivation. In contrast, we were not able to demonstrate a reduced rate of
relapse when the donor had KIR Cen-B, however relapse with a donor Cen-A
haplotype was a competing risk factor to poor overall survival. Here we show that
the presence of donor activating KIR led to improved outcome for the patient,
potentially through reduced relapse rates and decreased incidence of acute GvHD
translating to improved overall survival. This article is protected by copyright.
All rights reserved.
PMID- 29943501
TI - Tunable Chiroptical Properties from the Plasmonic Band to Metal-Ligand Charge
Transfer Band of Cysteine-Capped Molybdenum Oxide Nanoparticles.
AB - Understanding the interactions between a semiconducting nanocrystal surface and
chiral anchoring molecules could resolve the mechanism of chirality induction in
nanoscale and facilitate the rational design of chiral semiconducting materials
for chiroptics. Now, chiral molybdenum oxide nanoparticles are presented in which
chirality is transferred via a bio-to-nano approach. With facile control of the
amount of chiral cysteine molecules under redox treatment, circular dichroism
(CD) signals are generated in the plasmon region and metal-ligand charge-transfer
band. The obtained enhanced CD signals with tunable lineshapes illustrate the
possibility of using chiral molybdenum oxide nanoparticles as potentials for
chiral semiconductor nanosensors, optoelectronics, and photocatalysts.
PMID- 29943502
TI - The impact of installation of automatic milking system on production and
reproduction traits of dairy cows.
AB - The objective of the research was the evaluation of change in the traditional
milking system using automatic milking system in the scope of the selected
reproduction features of dairy cows of the Polish Holstein-Friesian breed. Animal
material consisted of 2,818 cows used on nine farms equipped with the automatic
milking system Astronaut A4 made by Lely. The cows were controlled in the scope
of services per conception, service period, length of pregnancy, calving interval
and calving to conception period, milk yield, protein and fat content obtained in
lactations of 305 days. The selected traits were observed between 2005 and 2015.
In this period, the milking system was changed from the conventional to automated
one. The collected data material was statistically processed, using the
multifactorial analysis of variance. The period between the first calving and the
second effective insemination was reduced by 11.8 days, and the period between
the second calving and the third effective insemination was shortened by 4 days
after the installation of the automatic milking system. The increase in milk
yield by 466 kg during 305-day lactation was observed among primiparous cows. The
percentage of protein and fat content in the researched groups decreased;
moreover, the fall of intergroup variability was noticeable, which may be a sign
of the levelling of the yield within the herd.
PMID- 29943503
TI - The influence of selective A1 and A2A receptor antagonists on the antidepressant
like activity of moclobemide, venlafaxine and bupropion in mice.
AB - OBJECTIVE: The main goal of our study was to investigate whether a selective
antagonism of the adenosine A1 or A2A receptors is able to enhance the
antidepressant activity of commonly prescribed drugs. MATERIALS AND METHODS: All
experiments were carried out on male Albino Swiss mice. The forced swim test and
the tail suspension test were used to evaluate the antidepressant-like potential.
Drug concentrations in animals' serum and brains were measured by high
performance liquid chromatography. KEY FINDINGS: The antidepressant potential of
moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg) and bupropion (10 mg/kg) was
enhanced by a co-administration with 3,7-dimethyl-1-propargylxanthine (DMPX; an
antagonist of adenosine A2A receptors; 3 mg/kg) or 8-cyclopentyl-1,3
dipropylxanthine (an antagonist of adenosine A1 receptors; 1 mg/kg). However,
significant interactions between the tested substances were detected only in the
experiments with DMPX. The nature of the observed interplays is rather
pharmacodynamic than pharmacokinetic, because neither serum nor brain
concentrations of the used drugs were significantly increased. CONCLUSIONS:
Blockage of the adenosine receptors (particularly the A2A subtypes) could be
considered in future as a novel, promising part of the combined antidepressant
therapy. However, further studies on this subject are needed.
PMID- 29943504
TI - Salvia miltiorrhiza enhances the survival of mesenchymal stem cells under
ischemic conditions.
AB - OBJECTIVES: To validate the enhanced therapeutic effect of Salvia miltiorrhiza
Bunge (SM) for brain ischemic stroke through the anti-apoptotic and survival
ability of mesenchymal stem cells (MSCs). METHODS: The viability and the
expression level of cell apoptotic and survival-related proteins in MSCs by
treatment of SM were assessed in vitro. In addition, the infarcted brain region
and the behavioural changes after treatment of MSCs with SM were confirmed in rat
middle cerebral artery occlusion (MCAo) models. KEY FINDINGS: We demonstrated
that SM attenuates apoptosis and improves the cell viability of MSCs. In the rat
MCAo model, the recovery of the infarcted region and positive changes of
behaviour are observed after treatment of MSCs with SM. CONCLUSIONS: The therapy
using SM enhances the therapeutic effect for brain ischemic stroke by promoting
the survival of MSCs. This synergetic effect thereby proposes a new experimental
approach of traditional Chinese medicine and stem cell-based therapies for
patients suffering from a variety of diseases.
PMID- 29943505
TI - Congenital syphilis as a clinical and histopathologic mimic of neonatal lupus.
PMID- 29943506
TI - Pt and Pt-Ni(OH)2 Electrodes for the Hydrogen Evolution Reaction in Alkaline
Electrolytes and Their Nanoscaled Electrocatalysts.
AB - The design and synthesis of Pt-based electrocatalysts for the hydrogen evolution
reaction (HER) are of great importance for the successful development of hydrogen
based alternative energy technologies. Although Pt is considered to be the most
active catalyst for the HER, its reaction performance is limited in alkaline
solutions owing to a slow rate for water dissociation. Therefore, many research
groups have intensively investigated reaction mechanisms and developed system
designs and efficient Pt-based catalysts to enhance the alkaline HER. Herein, we
summarize the catalytic surface specificity of Pt and Pt-Ni(OH)2 materials to
control the kinetics of the alkaline HER. In particular, we increase our
understanding of Ni(OH)2 -modified Pt surfaces and the corresponding nanoscaled
Pt-Ni(OH)2 electrocatalysts to improve the sluggish water-dissociation step, and
this knowledge will guide us to future sustainable energy applications of
advanced nanomaterials.
PMID- 29943507
TI - Dexamethasone impacts zinc levels in goats by regulating zinc transportation in
the colon and the metabolism in the liver.
AB - The aim of this study was to investigate the effects of dexamethasone (DEX) on
zinc metabolism in goats. In this study, 10 goats were randomly divided into two
groups. One group was injected with dexamethasone (Dex group) and the other group
was injected with saline (Con group). Dex treatment significantly decreased
hepatic zinc levels (p < .01) and increased Zn transporters 1 (ZNT-1) expression
(p < .05). The concentration of zinc in the cecal and colonic contents was
significantly increased (p < .05). However, zinc levels were increased only in
the colon tissues (p < .05) but not in the cecal tissues (p > .05). A dramatic
increase in Zrt-, Irt-related proteins 14 (ZIP-14) expression (p < .05) following
Dex treatment was also observed and likely induced the elevated zinc levels in
the colon, and a significant reduction in Zip-14 methylation (p < .05) may be
responsible for the observed increase in Zip-14 expression. Together, these
results indicate that Dex influences zinc homeostasis by increasing hepatic ZNT-1
and colonic ZIP-14 expression. Additionally, these results provide valuable
information for the clinical application of Dex.
PMID- 29943508
TI - Effects of Adrenaline on maternal and fetal fentanyl absorption in epidural
analgesia: A randomized trial.
AB - BACKGROUND: The combination of low-dose local anesthesia and lipophilic opioids
such as fentanyl is established as a standard solution for labor epidural
analgesia. Fentanyl increases efficacy, but may have negative effects on the
neonate in terms of reduced neonatal neurologic and adaptive capacity scores and
breast feeding. We hypothesized that addition of adrenaline 2 MUg/mL to a
solution of bupivacaine 1 mg/mL and fentanyl 2 MUg/mL would reduce the systemic
uptake of fentanyl, resulting in reduced serum fentanyl in the fetus at birth.
METHODS: Forty-one nulliparous women requesting epidural analgesia were
randomized to epidural analgesia with or without adrenaline. Blood samples were
drawn from the mother with regular intervals, and at delivery. An umbilical vein
blood sample (used as a proxy for fetal exposure) was drawn after clamping.
RESULTS: There were no significant differences between the groups in fentanyl
concentrations in the umbilical vein and maternal serum at birth. There was a
significantly lower mean area under the maternal serum-concentration curve for
the first 2 hours of treatment in the adrenaline group (mean difference 0.161
nmol h/L [0.034; 0.289], P = .015), implying slower systemic uptake in the
adrenaline group initially. There were no significant differences in treatment
duration, motor block, Apgar scores, umbilical pH and base excess, or mode of
delivery. CONCLUSIONS: The addition of adrenaline to an epidural solution
containing fentanyl lowered maternal systemic serum fentanyl concentration during
the first 2 hours, but did not lower serum fentanyl concentration in the
umbilical vein and mother at delivery.
PMID- 29943509
TI - Applications of systems modelling in obesity research.
AB - Obesity is a complex system problem involving a broad spectrum of policy, social,
economic, cultural, environmental, behavioural, and biological factors and the
complex interrelated, cross-sector, non-linear, dynamic relationships among them.
Systems modelling is an innovative approach with the potential for advancing
obesity research. This study examined the applications of systems modelling in
obesity research published between 2000 and 2017, examined how the systems models
were developed and used in obesity studies and discussed related gaps in current
research. We focused on the applications of two main systems modelling
approaches: system dynamics modelling and agent-based modelling. The past two
decades have seen a growing body of systems modelling in obesity research. The
research topics ranged from micro-level to macro-level energy-balance-related
behaviours and policies (19 studies), population dynamics (five studies), policy
effect simulations (eight studies), environmental (10 studies) and social
influences (15 studies) and their effects on obesity rates. Overall, systems
analysis in public health research is still in its early stages, with limitations
linked to model validity, mixed findings and its actual use in guiding
interventions. Challenges in theory and modelling practices need to be addressed
to realize the full potential of systems modelling in future obesity research and
interventions.
PMID- 29943510
TI - Inducing effects of cellulosic hydrolysate components of lignocellulose on
cellulosome synthesis in Clostridium thermocellum.
AB - Cellulosome is a highly efficient supramolecular machine for lignocellulose
degradation, and its substrate-coupled regulation requires soluble transmembrane
signals. However, the inducers for cellulosome synthesis and the inducing effect
have not been clarified quantitatively. Values of cellulosome production capacity
(CPC) and estimated specific activity (eSA) were calculated based on the primary
scaffoldin ScaA to define the stimulating effects on the cellulosome synthesis in
terms of quantity and quality respectively. The estimated cellulosome production
of Clostridium thermocellum on glucose was at a low housekeeping level. Both
Avicel and cellobiose increased CPCs of the cells instead of the eSAs of the
cellulosome. The CPC of Avicel-grown cells was over 20-fold of that of glucose
grown cells, while both Avicel- and glucose-derived cellulosomes showed similar
eSA. The CPC of cellobiose-grown cells was also over three times higher than
glucose-grown cells, but the eSA of cellobiose-derived cellulosome was 16% lower
than that of the glucose-derived cellulosome. Our results indicated that cello
oligosaccharides played the key roles in inducing the synthesis of the
cellulosome, but non-cellulosic polysaccharides showed no inducing effects.
PMID- 29943511
TI - Expression of melatonin and its related synthase and membrane receptors in the
oestrous corpus luteum and corpus luteum verum of sheep.
AB - Melatonin is an important factor involved in regulating reproduction; it is
synthesized enzymatically by the sequential action of melatonin-synthesizing
enzymes, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O
methyltransferase (HIOMT), and exerts its biological functions mainly through
receptor-mediated action. To evaluate the expression of melatonin, two melatonin
synthesizing enzymes (HIOMT and AANAT), and membrane receptors (MT1 and MT2) in
oestrous corpus luteum (CL) and CL verum of sheep (Ovis aries), we performed
ELISA, qRT-PCR, western blotting and immunohistochemistry. The quantitative
results showed that melatonin, HIOMT and AANAT levels in the CL verum were
significantly higher than those in oestrous CL (p < 0.05), whereas MT1 and MT2
exhibited no change between the oestrous CL and CL verum (p > 0.05); moreover,
the localization results showed that HIOMT, AANAT, MT1 and MT2 were mainly
expressed in large luteal cells (LLCs). In summary, the above results suggested
that sheep CL has potential for the synthesis of melatonin; meanwhile, they also
suggested that CL is one of the targets of melatonin. These results provide not
only a basis for whether sheep CL can synthesize melatonin but also provide a
reference for further study on the mechanism of melatonin in the CL.
PMID- 29943512
TI - Achieving Ultralow Wear with Stable Nanocrystalline Metals.
AB - Recent work suggests that thermally stable nanocrystallinity in metals is
achievable in several binary alloys by modifying grain boundary energies via
solute segregation. The remarkable thermal stability of these alloys has been
demonstrated in recent reports, with many alloys exhibiting negligible grain
growth during prolonged exposure to near-melting temperatures. Pt-Au, a proposed
stable alloy consisting of two noble metals, is shown to exhibit extraordinary
resistance to wear. Ultralow wear rates, less than a monolayer of material
removed per sliding pass, are measured for Pt-Au thin films at a maximum Hertz
contact stress of up to 1.1 GPa. This is the first instance of an all-metallic
material exhibiting a specific wear rate on the order of 10-9 mm3 N-1 m-1 ,
comparable to diamond-like carbon (DLC) and sapphire. Remarkably, the wear rate
of sapphire and silicon nitride probes used in wear experiments are either higher
or comparable to that of the Pt-Au alloy, despite the substantially higher
hardness of the ceramic probe materials. High-resolution microscopy shows
negligible surface microstructural evolution in the wear tracks after 100k
sliding passes. Mitigation of fatigue-driven delamination enables a transition to
wear by atomic attrition, a regime previously limited to highly wear-resistant
materials such as DLC.
PMID- 29943513
TI - Maturation ability after transfer of freeze-dried germinal vesicles from porcine
oocytes.
AB - The purpose of this study was to examine whether freeze-dried germinal vesicles
(GV) can be matured in vitro after being injected into enucleated fresh oocytes
in pigs as an alternative method for conservation of genetic resources. Although
no reduction of the size of GV (p = .094), resveratrol treatment significantly
enhanced the survival rates following GV transfer (GVT) (p < .001).
Supplementation with 100 or 200 mmol/L trehalose in freeze-drying medium
significantly increased the proportions of GVs with intact nuclear membrane and
DNA integrity compared with the control group. Following transfer of freeze-dried
GVs into enucleated fresh oocytes, the proportion of reconstructed oocytes
reached the metaphase-II stage (2.4% +/- 1.4%) was significantly lower (p < .05)
than that of the in vitro matured control group (83.2% +/- 2.5%), it was
comparable with the GVT control group (7.4% +/- 2.7%). The rates of freeze-dried
GVs with intact nuclear membrane and DNA stored at -20 degrees C for 5 days were
significantly higher (p < .05) than those at 4 degrees C and room temperature.
The rates of intact nuclear membrane and DNA in the freeze-dried GV stored for 15
or 30 days at -20, 4 degrees C and RT were not significantly different. In
conclusion, matured oocytes were produced derived from freeze-dried GVs.
PMID- 29943515
TI - So, you want to start a new nursing journal? Stop, read this first.
PMID- 29943514
TI - Targeting dyspnoea in patients with very severe COPD: Practical precision
medicine.
PMID- 29943516
TI - Leucocyte telomere length and paroxysmal atrial fibrillation: A prospective
cohort study and systematic review with meta-analysis.
AB - BACKGROUND: Telomere length is a surrogate marker of biological aging. Whether
telomere length predicts the risk of atrial fibrillation (AF) independently of
biological aging is controversial. We conducted a cohort study to examine the
relationship between telomere length and paroxysmal AF (PAF), followed by a
systematic review and meta-analysis of the published literature, incorporating
our own data. METHODS: DNA was extracted from peripheral blood. Leucocyte
telomere length was measured by a real-time polymerase chain reaction-based
method, normalized to a single copy gene, and presented as telomere/single gene
ratio (t/s). RESULTS: A total of 100 non-AF patients and 50 PAF patients (mean
age: 61.0 +/- 9.4 and 64.0 +/- 10.7 years, respectively) were included. T/s for
subjects without AF tended to be shorter than for those with AF (0.21 [0.06-0.36]
vs 0.28 [0.11-0.71], P = .077). T/s was associated with a 1.60-fold increase in
the risk of AF but this was not significant (95% CI: 0.988-2.597, P = .056). Our
meta-analysis confirms no difference in telomere length between AF and non-AF
patients and t/s was not associated with higher risk of AF in multivariate
analysis. CONCLUSIONS: Our prospective data showed that leucocyte telomere length
was similar between AF and non-AF patients but was significantly longer in male
patients with PAF than those without AF in our subgroup analysis. Our meta
analysis found that t/s did not predict AF. These findings support the notion
that chronological aging, but not markers of biological aging, predicts the risk
of AF.
PMID- 29943517
TI - Risk factors for developing diabetes after 3 years among community-dwelling
elderly with impaired fasting glucose.
AB - BACKGROUND: The aim of the present study was to examine the risk factors for
developing diabetes after 3 years in an elderly Chinese suburban population with
impaired fasting glucose (IFG). METHODS: The study population comprised residents
of the Hangu area of Tianjin, China, with IFG, aged >=60 years, who joined the
national free physical examination program (n = 328; mean [+/-SD] age 68.0 +/-6.1
years; 48.2% men). Diabetes was defined by self-report of a physician's diagnosis
or fasting plasma glucose (FPG) >=7.0 mmol/L; IFG was defined as FPG >=5.6 and <
7.0 mmol/L. Risk factors of incident diabetes at the 3-year follow-up were
analyzed individually using logistic regression analysis. RESULTS: Between
baseline and the 3-year follow-up, 56 subjects with IFG at baseline had developed
diabetes. After multivariate adjustment for demographic and clinical factors, the
incidence of diabetes increased with higher FPG (odds ratio [OR] 9.30, 95%
confidence interval [CI] 2.84-30.48), but decreased with the grip strength/weight
ratio (OR 0.88, 95% CI 0.82-0.94). Moreover, the combination of higher FPG and
lower grip strength/weight was associated with a higher incidence of diabetes
than higher FPG only or lower grip strength/weight (P < 0.05). CONCLUSION: The
present study indicates that higher FPG and lower muscle strength are associated
with glycemic deterioration among subjects with IFG after 3 years. The results
suggest that not only glucose levels, but also physical performance may be useful
markers of the risk of diabetes in this population.
PMID- 29943518
TI - Short-term effects of crisis response planning on optimism in a U.S. Army sample.
AB - AIM: This study examined the short-term effects of a brief crisis intervention on
optimism of acutely suicidal soldiers. METHODS: U.S. Soldiers (N = 97) presenting
for an emergency mental health appointment in a military emergency department or
behavioural health clinic were randomly assigned to treatment as usual standard
crisis response plan, or enhanced crisis response plan (E-CRP). This study is
used a subsample of the original clinical trial (n = 64) for those who completed
self-report measures of optimism (Life Orientation Test-Revised) prior to
receiving any intervention and a secondary self-report assessment one-month
following the intervention. RESULTS: Results indicate that individuals with low
baseline optimism who received the E-CRP had significant increases in optimism 1
month post-intervention. CONCLUSION: This provides evidence that discussing a
patient's reasons for living during a CRP increases optimism in those high-risk
patients with the lowest baseline optimism.
PMID- 29943519
TI - Total Synthesis and Biological Evaluation of the Glycosylated Macrocyclic
Antibiotic Mangrolide A.
AB - The macrocyclic antibiotic mangrolide A has been described to exhibit potent
activity against a number of clinically important Gram-negative pathogens.
Reported is the first enantioselective total synthesis of mangrolide A and
derivatives. Salient features of this synthesis include a highly convergent
macrocycle preparation, stereoselective synthesis of the disaccharide moiety, and
two beta-selective glycosylations. The synthesis of mangrolide A and its
analogues enabled the re-examination of its activity against bacterial pathogens,
and only minimal activity was observed.
PMID- 29943520
TI - The Effect of Addition of Calcium Phosphate Particles to Hydrogel-Based Composite
Materials on Stiffness and Differentiation of Mesenchymal Stromal Cells toward
Osteogenesis.
AB - The stiffness of a hydrogel has a significant role on the mechanical stability of
a scaffold. However, the stiffness of pure hydrogels can be tuned only within a
limited range. Herein, it is hypothesized that the range of hydrogel stiffness
can be greatly increased by the addition of calcium phosphate particles and that
such composites promote the osteogenic differentiation of human mesenchymal stem
cells (hMSCs). Beta-tricalcium phosphate (beta-TCP) particles are incorporated at
concentrations of 0.5 and 5 mg mL-1 into various agarose and agarose-collagen
blends. These composites are characterized with respect to stiffness, viscosity,
degradation, cell morphology, viability, and osteogenesis. The osteogenic hMSCs
in less stiff composites with 0.5 mg mL-1 beta-TCP show the highest alkaline
phosphatase expression compared to blends without beta-TCP and stiffer composites
with 5 mg mL-1 beta-TCP. Quantitative polymerase chain reaction also shows higher
expression of ALP, RUNX2, and collagen I by hMSCs in less stiff composites with
0.5 mg mL-1 beta-TCP compared to blends without beta-TCP and stiffer composite
blends. It is concluded that by addition of calcium phosphate to specific
hydrogels the stiffness can be tuned in a desired range and thus the osteogenic
differentiation of embedded hMSCs can be better controlled and adjusted compared
to pure hydrogels.
PMID- 29943521
TI - Caffeine alters the effects of bone marrow-derived mesenchymal stem cells on
neutrophils.
AB - BACKGROUND: It has been shown that mesenchymal stem cells (MSCs) express all four
adenosine receptors' subtypes, and stimulation of these receptors plays an active
role in bone marrow-derived mesenchymal stem cell proliferation and
differentiation. The interaction between MSCs and immunocytes, such as
neutrophils, has been investigated in some recent studies. OBJECTIVES: This study
was carried out to investigate the effects of caffeine as an adenosine antagonist
on the effects of bone marrow-derived MSCs on neutrophils. MATERIAL AND METHODS:
Mesenchymal stem cells were isolated from the bone marrow of rats and pulsed with
different concentrations of caffeine (0.1, 0.5 and 1 mM) at different times (24,
48 and 72 h). Mesenchymal stem cells were co-cultured with neutrophils for 4 h
and the functions of neutrophils were evaluated. RESULTS: The findings showed
that MSCs pulsed with caffeine at low to moderate concentrations preserved the
neutral red uptake by neutrophils and established the MSCs' ability to protect
neutrophils from apoptosis. Mesenchymal stem cells treated with caffeine
increased the phagocytosis of neutrophils and simultaneously diminished the
production of potentially harmful reactive oxygen substances, more profound than
MSCs without treatment. Nevertheless, a high concentration of caffeine could
interfere with some aspects of the crosstalk between MSCs and neutrophils.
CONCLUSIONS: These findings may offer new insight into the potential mechanisms
underlying the immunomodulatory effects of caffeine.
PMID- 29943522
TI - Does preemptive gabapentin modulate cytokine response in total knee arthroplasty?
A placebo controlled study.
AB - BACKGROUND: Gabapentin, as a structural analogue of gamma-aminobutyric acid, has
been investigated to provide pain relief in the early postoperative period
following various surgical interventions. OBJECTIVES: The objective of this study
was to investigate whether preemptive oral administration of gabapentin 800 mg
can reduce postoperative pain and modulate the inflammatory cytokine response in
comparison to placebo in patients undergoing total knee arthroplasty under
general anesthesia. MATERIAL AND METHODS: Fifty-two patients were randomly
divided into 2 groups before surgery, either to receive peroral gabapentin 800 mg
or placebo drug, 1 h before surgery. All patients had general anesthesia with
endotracheal intubation, in a standardized fashion, by the same anesthetist.
Thirty min before completion of surgery, intramuscular diclofenac sodium 75 mg
was administered. Following extubation, visual analogue pain scale (VAS) scores
and additional analgesic requirements were recorded at 15 min at post-anesthesia
care unit (PACU), and at 4th and 24th h postoperatively. Plasma levels of
interleukin 6 (IL-6), and tumor necrosis factor R (TNF-R) were measured at
predetermined time points (T0 1 h before administration of gabapentin, T1 at
postoperative the 4th h mark, and T2 at postoperative at the 24th h mark).
RESULTS: The VAS scores at postoperative 4th h were significantly higher in
placebo and gabapentin groups compared with VAS scores at PACU and at 24th h. The
groups did not differ in terms of additional analgesic requirements. In
gabapentin group, IL-6 levels at T1 and T2 were significantly lower in comparison
to values measured in placebo group at the same time points. This difference was
not significant in TNF-R levels between the groups. CONCLUSIONS: Though
preemptive oral gabapentin administration did not reduce postoperative pain and
analgesic requirements in total knee arthroplasty surgery, it attenuated IL-6
production on the first postoperative day.
PMID- 29943523
TI - A pilot data analysis of a metabolomic HPLC-MS/MS study of patients with COPD.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous
condition with multiple clinical faces. Metabolomic profiling studies small
molecules present in biological samples by combined use of chromatography with
mass spectrometry. OBJECTIVES: The goal of our work was to perform a high
performance liquid chromatography combined with tandem mass spectrometry (HPLC
MS/MS) metabolomic study to compare the concentrations of metabolites in COPD
patients and in controls. MATERIAL AND METHODS: Participants were recruited at
the University Hospital, Hradec Kralove, Czech Republic, with the approval of the
ethics committee. The analysis of blood samples was performed at Health Sciences
Center (HSC) in Kuwait. The blood samples were analyzed for concentrations of
acylcarnitines and amino acids by high performance liquid chromatography (Waters
2690 HPLC; Waters, Milford, USA) and a triple-quadruple tandem mass spectrometer
(Quattro LC, Micromass, Manchester, United Kingdom). RESULTS: Groups of 10
subjects with COPD and 10 healthy controls were analyzed. Carnitine analysis
showed that the free carnitine to acylcarnitine ratio (C0/AC ratio) was
significantly lower in COPD (0.58 MUM/L) compared to the controls (0.73 MUM/L; p
= 0.002). The mean C8/C2 ratio in the COPD group was significantly higher (0.03
MUM/L) - in the control group it was 0 MUM/L (p = 0.03). Amino acid analysis
showed lower levels of phenylalanine in the COPD group (22.05 MUM/L) compared to
the controls (30.05 MUM/L; p = 0.008). The alanine concentrations were
significantly lower in the COPD group (173 MUM/L) than in the control group (253
MUM/L; p = 0.001). The pyroglutamate levels were higher in COPD (1.58 MUM/L) than
in the controls (1 MUM/L; p = 0.040). CONCLUSIONS: The carnitine and
acylcarnitine levels in COPD subjects in this study possibly indicate a
predisposition to atherosclerosis as a result of inadequate beta-oxidation of
fatty acids and show the presence of oxidative stress. Furthermore, the high
sensitivity to changes in circulating amino acid levels may allow us to detect
subclinical malnutrition and take early preventative interventions such as
nutritional supplementation and patient education.
PMID- 29943524
TI - Bileaflet pericardial patch repair for rheumatic mitral valve disease.
AB - Surgical repair in rheumatic mitral valve disease is technically challenging as
the disease affects both valvular and subvalvular structures. Due to the
resultant shortage of pliable valve tissue, pericardial patch techniques are
progressively used to restore normal valve function. This makes mitral valve
repair possible even in the most severe forms of rheumatic mitral valve disease.
In this tutorial, we report a case of mitral valve repair with a bileaflet
(decellularized) pericardial patch in a patient with severe rheumatic mitral
valve disease.
PMID- 29943525
TI - Reconstruction of high-resolution early-photon tomography based on the first
derivative of temporal point spread function.
AB - For fluorescence molecular tomography, higher spatial resolution can be achieved
using minimally scattered early photons. Conventional reconstruction methods of
early photon tomography (EPT) are based on the integral of temporal point spread
function (TPSF), which may lead to poor image quality due to systematic noise and
time mismatch between the TPSF data and forward model. The derivative of the
rising portion of TPSF is proposed to be used in EPT to increase the performance
of reconstruction because the derivative is less sensitive to noise and time
mismatch than the integral. A method based on projected Tikhonov regularization
with the reconstructed result of steepest descent algorithm as a priori
information is developed. Using the derivative of TPSF, the method can achieve
high spatial resolution in phantom experiments and is capable of separating
targets with an edge-edge distance of 1.5 mm.
PMID- 29943526
TI - In vivo multiphoton kinetic imaging of the toxic effect of carbon tetrachloride
on hepatobiliary metabolism.
AB - We used intravital multiphoton microscopy to study the recovery of hepatobiliary
metabolism following carbon tetrachloride (CCl4) induced hepatotoxicity in mice.
The acquired images were processed by a first order kinetic model to generate
rate constant resolved images of the mouse liver. We found that with progression
of hepatotoxicity, the spatial gradient of hepatic function disappeared. A CCl4
induced damage mechanism involves the compromise of membrane functions, resulting
in accumulation of processed 6-carboxyfluorescein molecules. At day 14 following
induction, a restoration of the mouse hepatobiliary function was found. Our
approach allows the study of the response of hepatic functions to chemical agents
in real time and is useful for studying pharmacokinetics of drug molecules
through optical microscopic imaging.
PMID- 29943527
TI - Image-guided filtering for improving photoacoustic tomographic image
reconstruction.
AB - Several algorithms exist to solve the photoacoustic image reconstruction problem
depending on the expected reconstructed image features. These reconstruction
algorithms promote typically one feature, such as being smooth or sharp, in the
output image. Combining these features using a guided filtering approach was
attempted in this work, which requires an input and guiding image. This approach
act as a postprocessing step to improve commonly used Tikhonov or total
variational regularization method. The result obtained from linear backprojection
was used as a guiding image to improve these results. Using both numerical and
experimental phantom cases, it was shown that the proposed guided filtering
approach was able to improve (as high as 11.23 dB) the signal-to-noise ratio of
the reconstructed images with the added advantage being computationally
efficient. This approach was compared with state-of-the-art basis pursuit
deconvolution as well as standard denoising methods and shown to outperform them.
PMID- 29943528
TI - [Research advance of influenza B viruses].
AB - Influenza B virus (IBV) is a segmented negative-strand RNA virus, which often
causes local outbreak or seasonal epidemic along with influenza A virus (IAV) in
the world. It is pathogenic to children, teenagers and elderly people and has a
higher mortality rate in children and adolescents, so it poses a serious threat
to public health and health. IBV is more likely to cause complications than IAV
and the disease burden of IBV even exceeds IAV in the epidemic season. Recently,
especially after winter of 2017, IBV has become the dominant strain in many areas
of our country and seriously affects people's health. In view of this, this
article reviews the structure, epidemiology, immunology and prevention of IBV,
aiming at enhancing public's perceptions of the virus and providing reference for
making strategies for prevention and control of influenza B.
PMID- 29943529
TI - [Molecular mechanisms underlying daptomycin resistance].
AB - Due to potent bactericidal activity and low rate of drug-resistance, daptomycin
is recognized as first line antibiotic to treat serious infections caused by drug
resistant Gram-positive pathogens. However, the incidence of daptomycin
resistance is increasing due to its widespread application. Alteration of cell
wall homeostasis and membrane phospholipid metabolism is involved in daptomycin
resistance. The unique mode of action underlying daptomycin resistance in
important pathogens, including Staphylococcus aureus and Enterococci, is
presented in this paper.
PMID- 29943530
TI - [Applications of simulated gastro-intestinal model in foodborne pathogens:
tolerance and pathogenesis].
AB - We evaluated the tolerance and pathogenesis of foodborne pathogens with a
simulated gastro-intestinal tract model that simulates the chemical, physical and
biological effects of human digestion process under laboratory conditions. This
could be used to study the tolerance, pathogenesis, gut microbiota interaction
and vaccine development of foodborne pathogens, so as to contribute to control
and treatment of foodborne pathogens. This review introduces the applications of
simulated gastro-intestinal tract model tp evaluate foodborne pathogens, which
includes in-vitro static gastro-intestinal model, in-vitro dynamic gastro
intestinal model, conventional animal model and humanized animal model. And the
concepts and characteristics of all models are described in detail. Also, the
shortcomings of existing models are analyzed, and improvements of artificial
gastro-intestinal tract model are prospected. In conclusion, this review could
provide comprehensive data for promoting the progress of studying tolerance and
pathogenesis of foodborne pathogens.
PMID- 29943531
TI - [Advances in haplotype analysis technique].
AB - Haplotype is the combination of a series of genetic mutations that coexist on a
single chromosome, each of which has its own unique haplotypes. As a common data
analysis method, the analysis of haplotype is effective for the localization of
heterozygosis SNPs on single chromosome, the excavation of disease genes and the
search of maladies treatments. It mainly includes indirect computational
inferential method and direct experimental method. In this review we introduced
various haplotype analysis methods and applications, especially two important
ones: single-molecule dilution and contiguity-preserving transposition sequencing
common technology. Meanwhile, further research prospects on haplotype sequencing
were proposed.
PMID- 29943532
TI - [Progress in biosynthesis of santalene and santalol].
AB - Santalene and santalol are the main components of valuable perfume sandalwood
essential oil, and have good antibacterial, anti-oxidation and anti-tumor
activities. Commercial sandalwood essential oil is mainly extracted from
sandalwood tree that grows slowly and is difficult to cultivate. In addition, the
extraction recovery of sandalwood essential oil from sandalwood tree is too low
to meet the market demand. These factors make sandalwood essential oil expensive.
An option is to use genetic engineering and molecular biological methods to
heterologously express related synthase of santalene and santalol in microbial
host. In this paper, the biosynthesis progress of santalene and santalol
synthase, as well as the optimization of mevalonate metabolic pathways in the
hosts are summarized. Furthermore, the strategies of applying protein engineering
technology to carry out orthomutation of santalene synthase were also discussed,
to provide reference for the optimal biosynthesis of santalene and santalol.
PMID- 29943533
TI - [Roles and mechanisms of netrins in cancer development].
AB - As secreted protein and membrane-bound proteins, netrins play important roles in
biological processes such as neural cell migration, differentiation and
apoptosis. Netrins were thought to guide axon outgrowth and central nervous
system morphology since they were discovered. Besides, they also participate in
physiological processes such as cell adhesion, migration, differentiation,
angiogenesis, lymph angiogenesis, and inflammation in non-neural tissues. Recent
studies showed that netrins also involved in the regulation of initiation and
development of various tumors including colorectal cancer, pancreatic ductal
adenocarcinoma. Because of the functional diversity of netrins and the different
biological effects of different receptors in tumor tissue, the specific mechanism
of their action in tumors remains unclear. Based on current research progress of
our group, this review summed up recent research findings on netrins in relation
to cancer biology, suggested possible mechanisms, and discussed the implications
in cancer research and intervention.
PMID- 29943534
TI - [Construction of recombinant PRRSV ORF5 gene by DNA shuffling technique].
AB - Recombinant PRRSV ?2ORF5 gene was constructed using DNA shuffling from four
genetically different strains of PRRSV to study its heterologous cross
neutralizing ability. The ?2ORF5 mutant gene was cloned into the vector pET-32a
and transferred into E. coli BL21. SDS-PAGE confirmed that the molecular weight
of the recombinant ?2ORF5 was about 42 kDa, consistent with the predicted result.
Then the purified recombinant protein was injected into BALB/c mouse to obtain
polyclonal antibody. Western blotting analysis with mouse-anti-?2ORF5 polyclonal
serum indicated that the parental virus recombinant GP5 protein reacted with the
specific antibodies. Four parental viruses could be inhibited by the anti-?2ORF5
polyclonal antibody and the inhibition rates were higher than 53%. This work has
laid a foundation for further development vaccine for PRRSV.
PMID- 29943535
TI - [Genome mining and characterization of a new mandelate racemase].
AB - Racemases have been applied for the synthesis of enantiomerically pure compounds
through the deracemization methods. Mandelate racemase from Pseudomonas putida
was the only enzyme that catalyzes the interconversion of mandelate enantiomers.
Using genome mining approaches, we identified 9 mandelate racemases (MRs). A
novel racemase named ArMR with higher activity and better soluble protein
expression, was isolated from Agrobacterium radiobacter. ArMR displayed the
optimum catalytic activity at 50 C, pH 7.8 in Tris-HCl buffer. The half-life of
ArMR at 50, 40 and 30 C was 0.17, 27.2 and 70.7 h, respectively. KM parameter of
ArMR towards (R)- and (S)-mandelic acid was 1.44 and 0.81 mmol/L, respectively;
the corresponding kcat value was 410 s-1 and 218 s-1. In addition, KM of ArMR
towards (R)- and (S)-2-chloro mandelic acid was 6.48 and 6.37 mmol/L, and the
corresponding kcat value 0.22 s-1 and 0.23 s-1, respectively. Meanwhile, Mg2+ and
Mn2+ could activate the enzyme whereas Zn2+ inactivated the enzyme completely.
Discovery of more novel MRs provides supports further research and development of
these racemases.
PMID- 29943536
TI - [Improvement of inhibitors tolerance of Saccharomyces cerevisiae by
overexpressing of long chain sphingoid kinases encoding gene LCB4].
AB - By-products released from pretreatment process of lignocellulose seriously hinder
the development of cellulosic fuel ethanol. Therefore, the great way to increase
the efficiency of cellulosic ethanol production is improvement of Saccharomyces
cerevisiae tolerance to these inhibitors. In this work, the effects of LCB4 gene
overexpression on cell growth and ethanol fermentation in S. cerevisiae S288C
under acetic acid, furfural and vanillin stresses were studied. Compared to the
control strain S288C-HO, the recombinant strain S288C-LCB4 grew better on YPD
solid medium containing 10 g/L acetic acid, 1.5 g/L furfural and 1 g/L vanillin.
Ethanol yields of recombinant strain S288C-LCB4 were 0.85 g/(L.h), 0.76 g/(L.h)
and 1.12 g/(L.h) when 10 g/L acetic acid, 3 g/L furfural and 2 g/L vanillin were
supplemented into the fermentation medium respectively, which increased by 34.9%,
85.4% and 330.8% than the control strain S288C-HO. Meanwhile, ethanol
fermentation time was reduced by 30 h and 44 h under furfural and vanillin
stresses respectively. Further metabolites analysis in fermentation broth showed
that the recombinant strain produced more protective compounds, such as glycerol,
trehalose and succinic acid, than the control strain, which could be the reason
for enhancing strain tolerance to these inhibitors from pretreatment process of
lignocellulose. The results indicated that overexpression of LCB4 gene could
significantly improve ethanol fermentation in S. cerevisiae S288C under acetic
acid, furfural and vanillin stresses.
PMID- 29943537
TI - [Enhanced production of bacitracin by knocking out of amino acid permease gene
yhdG in Bacillus licheniformis DW2].
AB - Bacitracin is a broad-spectrum polypeptide antibiotic, which is formed by 11
amino acids residues. Precursor amino acids supply might be the limit factor
during bacitracin fermentation. First, our results demonstrated that increasing
Ile and Leu supplies were regarded as the efficient strategies for the enhanced
titer of bacitracin. Then, the amino acid permease YhdG, which was identified as
the BCAA permease, was deleted and overexpressed in DW2, respectively. Our
results showed that knocking out of permease YhdG could improve bacitracin
production remarkablely. The bacitracin titer of the yhdG deficient strain
DW2DeltayhdG reached 917.35 U/mL by flask fermentation, increased by 11% compared
with that of DW2. In addition, the bacitracin titer was decreased by 25% in the
YhdG overexpressed strain. Meanwhile, the intracellular concentrations of BCAA
were higher than DW2 during the biosynthesis of bacitracin. The above results
suggested that the permease YhdG might act as an exporter for branched chain
amino acids in B. licheniformis DW2. Taken together, the increasing intracellular
concentrations of branched chain amino acids by deleting amino acid permease YhdG
could improve bacitracin titer. This study provided a new strategy for high-level
production of bacitracin.
PMID- 29943538
TI - [Cloning and analysis of a powdery mildew responsive gene CmSAMDC from Cucumis
melo L.]
AB - In order to investigate the effect of S-adenosylmethionine decarboxylase (SAMDC)
gene in melon resistance to powdery mildew, according to the previous results of
EST sequences from cDNA-AFLP library and the melon genome sequence data, the
SAMDC gene was isolated from Chinese wild melon clone 'Yuntian930' by RT-PCR and
designated as CmSAMDC (GenBank Accession No. KF151861). The mORF (main open
reading frame) was 1 095 bp encoding 364 amino acids with a molecular mass of 40
kDa. The predicted protein sequence showed high similarity with Cucumis sativus
and Citrofortunella microcarpa. The SDS-PAGE showed that the expression protein
was a fusion protein with the molecular weight of 40 kDa, which perfectly matched
the mass calculated from the amino acid sequence. Quantitative real-time PCR
analysis indicated that the expression level of CmSAMDC reached a maximum at 48
hpi (hours post inoculation) that over 7-fold to 0 hpi, and the expression of
CmSAMDC was also detected in tendril, root, leaf and stem. These results indicate
that CmSAMDC gene may play protective roles in melon resistance to powdery mildew
infection.
PMID- 29943539
TI - [Separation and identification of differential protein in the insect-resistant
and insect-susceptible mungbean].
AB - In order to find the insect-resistant composition and differentially expressed
proteins of mungbean, Jinlv No.7, B20 and Weilv 2117 were used as experimental
materials, and the differential proteins and functions of mungbean varieties that
are resistant and susceptible to bruchids were compared and analyzed by two
dimensional gel electrophoresis (2-DE) and identified by mass spectrometry. Among
the samples, 15 protein spots showed a more than 2.5 times reproducible up
regulated, significance 6 of them were successfully identified by the database,
and involved three kinds of proteins. They are the alpha and beta subtype 8S
globulin, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBis CO) subunits
binding protein and the precursor peptide chains for amylase inhibitor and
trypsin inhibitor. The protein expressions of B49 (alpha subtype 8S globulin) and
B31 (RuBis CO subunits binding protein) of insect-resistant mungbean were 10 000
and 23 times higher than that of insect-susceptible mungbeans. It stunted the
growth and even death of the Callosobruchus chinensis L. that alpha and beta
subtype 8S globulin and RuBis CO subunits binding protein and precursor peptide
chains for amylase inhibitor and trypsin inhibitor of insect-resistant mungbean,
the bruchid resistance effect of these three proteins need to further verified in
terms of the quantity and the combined effect.
PMID- 29943540
TI - [Fermentation of sheep bone enzymatic hydrolysates by Lactobacillus plantarum].
AB - In order to improve the nutritional value and bio-availability of sheep bone
enzymatic hydrolysates, we tried to ferment the hydrolysates with lactic acid
bacteria (LAB) to enhance free Ca2+, to generate oligopeptide and antioxidative
activity. First, we isolated 7 LAB strains from commercial starters and selected
Lactobacillus plantarum as the starter for its highest protease-producing
ability. The content of released Ca2+ was evaluated when the fermenting
conditions were optimized by the method of responsive surface design. When
supplemented with 1% maltose and inoculated 4% L. plantarum, at initial pH 5.5
and 37 C for 14 h, Ca2+ content in the hydrolysates increased significantly
(P<0.05), as well as the generation oligopeptide (P<0.01), and the content of
hydroxyproline (P<0.01). The count of L. plantarum in the fermented hydrolysates
reached to 94.6*108 CFU/mL. L. plantarum fermentation significantly enhanced the
ability to scavenge free radicals DPPH, .OH and O2-. (P<0.01, P<0.05). Therefore,
fermenting sheep bone hydrolysates by L. plantarum can increase free Ca2+,
oligopeptide and antioxidative ability.
PMID- 29943541
TI - [PPP2R2A binds and dephosphorylates GFPT2 in breast cancer cells].
AB - PPP2R2A is one of the regulatory subunits of the PP2A phosphatase complexes, and
previous studies showed that its upregulation promotes cancer cell survival and
growth. In this research, we used the tandem affinity purification and the HPLC
Chip-ESI/MS/MS mass spectrometry to screen the PPP2R2A-binding proteins and the
results indicated that the GFPT-1/-2 were the potential partners of PPP2R2A. We
further validated the interaction between PPP2R2A and GFPT-1/-2 through GST Pull
down, co-immunoprecipitation and immunofluorescence assays. And we found that
knockdown of PPP2R2A by lentivirus-mediated shRNA enhanced the phosphorylation of
GFPT2, whereas the phosphorylation of GFPT1 had no significant change. GFPT2 is a
rate-limiting enzyme in the hexosamine pathway. Our results showed that the
knockdown of PPP2R2A promoted the total cellular O-GlcNAcylation in MDA-MB-231
breast cancer cells. These results suggest that PPP2R2A interacts with GFPT1/2,
and leads to the phosphorylation of GFPT2, which can regulate the cellular O
GlcNAcylation.
PMID- 29943542
TI - [Effects of recombinant human interferon beta1a on the chondrogenic
differentiation of human bone marrow mesenchymal stem cell].
AB - Recombinant human interferon beta (rhIFN-beta) is a glycoprotein produced by
genetically engineered cells and has anti-virus, anti-tumor and immunoregulation
functions. Although studies have shown that other subtypes of IFN such as IFN
gamma affects cell proliferation and differentiation to some extent, the effect
of rhIFN-beta on chondrogenic differentiation of human bone marrow mesenchymal
stem cells (hMSCs) is less known. In this study we studied the effect of rhIFN
beta on the chondrogenic differentiation of hMSCs by inducing hMSCs into
cartilage pellet via adding IFN-beta1a into regular TGF-beta3 chondrogenic
differentiation medium. We collected the induced pellets and then detected GAG
content, assessed pellets size, observed agreecan using alcian blue staining, and
analyzed the expression of Sox and CollangenIIusing real-time PCR and Western
blotting. Addition of 100 ng/mL IFN-beta1a to regular TGF-beta3 chondrogenic
differentiation medium could improve the concentration of GAG, increase the size
of pellets, promote the formation of aggrecan and up-regulate the expression of
CollangenII and Sox9. IFN-beta1a combined with TGF-beta3 could promote
chondrogenic differentiation of hMSCs.
PMID- 29943543
TI - [An improved method for stem cell derivation from human great saphenous vein].
AB - The objectiue was to explore how to improve stem cell derivation from human great
saphenous vein. After the saphenous vein was cut into small pieces, the cells of
the vessel wall were obtained by tissue adherent method and digestion with type
II collagenase. The morphological changes of blood vessel wall were observed
under inverted microscope. The survival of vascular wall cells was assessed by
trypan blue staining. Stem cells doubly positive for CD34 and CD117 were sorted
out by immunofluorescent staining and flow cytometry. The cells obtained by
tissue adherence method exhibited signs of fibrotic changes and aging at the
third passage (P3), while the cells extracted by enzymatic digestion still showed
colony-like growth. Survival rates of these two groups of cells were (91.7+/
1.2)% and (97.2+/-0.7)%, (P=0.005). The results of flow cytometry showed that the
positive rates of CD34 and CD117 double positive cells in these two groups were
(0.16+/- 0.05)% and (0.44+/-0.07)%, respectively, with statistical significance
(P=0.005). Immunofluorescent staining showed that the positive rates of double
positive stem cells in the two groups were (89.41+/-2.06)% and (94.03+/-1.83)%,
P<0.05 one week after the sorted stem cells were cultured. The positive rates of
CD31, VEGF2 and SMA in the stem cells determined by flow cytometry were (0.12+/
0.01)%, (0.19+/-0.02)% and (0.45+/-0.01)%, respectively, which were not
statistically different from those of the control groups. This could rule out
substantial inclusion of mature endothelial cells and smooth muscle cells. Tube
forming experiment confirmed that these vascular stem cells had developmental
plasticity. More viable and morphologically healthy vascular stem cells can be
derived by enzymatic digestion. These cells can be widely used in clinical and
basic research.
PMID- 29943544
TI - [Differentiation of human pluripotent stem cells into red blood cells].
AB - At present, the experimental technique to produce human red blood cells in vitro
is complicated, and in order to optimize the induction steps, human pluripotent
stem cells were differentiated into red blood cells through two induction steps.
First, human pluripotent stem cells (including Rh negative A type umbilical cord
mesenchymal stem cells (hUCMSCRh-A) and human iPS cells (hiPS)) were
differentiated into CD31+ and CD34+ cells in BVF medium. PCR and flow cytometry
were used to exam the expression of CD31 and CD34. We found that hUCMSCRh-A
derived CD31+ and CD34+ cells were 5.3% and 22.7%, respectively; hiPS derived
CD31+ and CD34+ cells were 31.2% and 8.2%, respectively. For the second induction
step, the obtained CD31+ and CD34+ cells were differentiated into mature
erythrocytes for 36 days under the addition of various growth factors. Through
Giemsa staining, we found that the obtained mature erythrocytes were similar in
morphology and size to normal human erythrocytes, and some obtained erythrocytes
were enucleated. Globin expression was detected by real time RT-PCR, and the
expression of beta-globin was more than 20%. The obtained erythrocytes are
collected into the centrifuge tube, and then erythrocytes were naturally settled
and showed the red color. Our findings provide a novel and effective method for
the quantity generation of human red blood cells in vitro.
PMID- 29943545
TI - [Regression analysis to select native-like structures from decoys of antigen
antibody docking].
AB - Given the increasing exploitation of antibodies in different contexts such as
molecular diagnostics and therapeutics, it would be beneficial to unravel
properties of antigen-antibody interaction with modeling of computational protein
protein docking, especially, in the absence of a cocrystal structure. However,
obtaining a native-like antigen-antibody structure remains challenging due in
part to failing to reliably discriminate accurate from inaccurate structures
among tens of thousands of decoys after computational docking with existing
scoring function. We hypothesized that some important physicochemical and
energetic features could be used to describe antigen-antibody interfaces and
identify native-like antigen-antibody structure. We prepared a dataset, a subset
of Protein-Protein Docking Benchmark Version 4.0, comprising 37 nonredundant 3D
structures of antigen-antibody complexes, and used it to train and test
multivariate logistic regression equation which took several important
physicochemical and energetic features of decoys as dependent variables. Our
results indicate that the ability to identify native-like structures of our
method is superior to ZRANK and ZDOCK score for the subset of antigen-antibody
complexes. And then, we use our method in workflow of predicting epitope of anti
Ebola glycoprotein monoclonal antibody-4G7 and identify three accurate residues
in its epitope.
PMID- 29943546
TI - [Expression and identification of an antimicrobial peptide VIP in Pichia
pastoris].
AB - With the sequence of the vasoactive intestinal peptiepeptide (VIP) from humans
and according to the condon bias of Pichia pastoris, we designed PCR primers of
VIP and obtained the sequence of VIP by SOE-PCR. Then VIP gene was cloned into
Pichia pastoris secretory expression vector and the cell secretary system GS115
pPICZalphaA-vip was constructed. The recombinant strain was induced by methanol
for 96 hours, and we collected the supernatant and identified the VIP by mass
spectrometry. The molecular weight of VIP was consistent with theoretical
molecular weight. The final result showed that the target peptide VIP was
successfully expressed. The experimental investigations of agarose gel diffusion
revealed that the recombinant expression modified VIP had relatively strong
antibacterial activity to E. coli ATCC25922 and S. aureus ATCC25923. The minimal
inhibitory concentration (MIC) of VIP to E. coli ATCC25922 and S. aureus
ATCC25923 was 8 mmol/L and 16 mmol/L. Further cytotoxicity and hemolytic
experiments indicated that recombinant VIP was non-toxic to normal cells NCM460
and IPEC-J2, had little hemolysis activity to SD rat erythrocytes. Meanwhile, by
transmission electron microscopy, we found that VIP mainly inhibited bacteria by
disrupting the cell membrane. These experiments established a useful system for
further studies, application and mass production of antimicrobial peptide VIP.
PMID- 29943547
TI - [Establishment of time-resolved fluorescence immunochromatographic assay for
detection of carbohydrate antigen 19-9].
AB - To establish a time-resolved fluorescence immunochromatographic assay for
quantitative determination of carbohydrate antigen 19-9 (CA19-9) in serum, we
prepared CA19-9 test strips by integrating double-antibody sandwich method and
fluorescence immunochromatography technique. Carboxy fluorescent microspheres and
nitrocellulose membrane were used as carriers for labeling and coating CA19-9
pairing antibodies. We optimized the process by adjusting the amount of labeling
and coating antibody. According to the linear range, lowest detection limit and
precision, We evaluated the time-resolved fluorescence immunochromatographic
assay of CA19-9. When the amount of labeled antibody was 80 MUg for 20 MUL
fluorescent microspheres, and the concentration of coated antibody on the test
line was 1.5 mg/mL, the optimal reaction time was 15 minutes. Assay linear range
was 12.5 to 800 U/mL and the minimum detection limit was 6.32 U/mL. The Within
run and between-run coefficient of variation were less than 15%. Average recovery
rate was 101%. By detecting 50 clinical samples in parallel with Roche
electrochemical luminescence detection kit, correlation coefficient was 0.980 6.
The experiment, initially established a fluorescence immunochromatographic
detection method to quantitative detection of serum CA19-9, which has a good
clinical application prospect.
PMID- 29943548
TI - Fulminant cytomegalovirus infection in a preterm newborn.
PMID- 29943549
TI - Should children over 12 years have an EEG after a single unprovoked epileptic
seizure?
PMID- 29943550
TI - Videogames unmask hypertension in children.
PMID- 29943551
TI - Dietary Supplementation with Raspberry Extracts Modifies the Fecal Microbiota in
Obese Diabetic db/db Mice.
AB - Raspberries are polyphenol-rich fruits with the potential to reduce the severity
of the clinical signs associated with obesity, a phenomenon that may be related
to changes in the gut microbiota. The aim of this study was to investigate the
effect of raspberry supplementation on the fecal microbiota using an in vivo
model of obesity. Obese diabetic db/db mice were used in this study and assigned
to two experimental groups (with and without raspberry supplementation). Fecal
samples were collected at the end of the supplementation period (8 weeks) and
used for bacterial 16S rRNA gene profiling using a MiSeq instrument (Illumina).
QIIME 1.8 was used to analyze the 16S data. Raspberry supplementation was
associated with an increased abundance of Lachnospiraceae (p = 0.009), a very
important group for gut health, and decreased abundances of Lactobacillus,
Odoribacter, and the fiber degrader S24-7 family as well as unknown groups of
Bacteroidales and Enterobacteriaceae (p < 0.05). These changes were enough to
clearly differentiate bacterial communities accordingly to treatment, based on
the analysis of UniFrac distance metrics. However, a predictive approach of
functional profiles showed no difference between the treatment groups. Fecal
metabolomic analysis provided critical information regarding the raspberry
supplemented group, whose relatively higher phytosterol concentrations may be
relevant for the host health, considering the proven health benefits of these
phytochemicals. Further studies are needed to investigate whether the observed
differences in microbial communities (e.g., Lachnospiraceae) or metabolites
relate to clinically significant differences that can prompt the use of raspberry
extracts to help patients with obesity.
PMID- 29943553
TI - Cofactor Regeneration Using Permeabilized Escherichia coli Expressing NAD(P)+
Dependent Glycerol-3-Phosphate Dehydrogenase.
AB - Oxidoreductases are effective biocatalysts, but their practical use is limited by
the need for large quantities of NAD(P)H. In this study, a whole-cell biocatalyst
for NAD(P)H cofactor regeneration was developed using the economical substrate
glycerol. This cofactor regeneration system employs permeabilized Escherichia
coli cells in which the glpD and gldA genes were deleted and the gpsA gene, which
encodes NAD(P)+-dependent glycerol-3-phosphate dehydrogenase, was overexpressed.
These manipulations were applied to block a side reaction (i.e., the conversion
of glycerol to dihydroxyacetone) and to switch the glpD-encoding enzyme reaction
to a gpsA-encoding enzyme reaction that generates both NADH and NADPH. We
demonstrated the performance of the cofactor regeneration system using a lactate
dehydrogenase reaction as a coupling reaction model. The developed biocatalyst
involves an economical substrate, bifunctional regeneration of NAD(P)H, and
simple reaction conditions as well as a stable environment for enzymes, and is
thus applicable to a variety of oxidoreductase reactions requiring NAD(P)H
regeneration.
PMID- 29943554
TI - Structures of Zymomonas 2-Keto-3-Deoxy-6-Phosphogluconate Aldolase with and
without a Substrate Analog at the Phosphate-Binding Loop.
AB - 2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, which catalyzes aldol cleavage
and condensation reactions, has two distinct substrate-binding sites. The
substrate-binding mode at the catalytic site and Schiff-base formation have been
well studied. However, structural information on the phosphate-binding loop (P
loop) is limited. Zymomonas mobilis KDPG aldolase is one of the aldolases with a
wide substrate spectrum. Its structure in complex with the substrate-mimicking 3
phosphoglycerate (3PG) shows that the phosphate moiety of 3PG interacts with the
P-loop and a nearby conserved serine residue. 3PG-binding to the P-loop replaces
water molecules aligned from the P-loop to the catalytic site, as observed in the
apo-structure. The extra electron density near the P-loop and comparison with
other aldolases suggest the diversity and flexibility of the serine-containing
loop among KDPG aldolases. These structural data may help to understand the
substrate-binding mode and the broad substrate specificity of the Zymomonas KDPG
aldolase.
PMID- 29943556
TI - Antimicrobial Effect of 2-Phenylethynyl-Butyltellurium in Escherichia coli and
Its Association with Oxidative Stress.
AB - This study aimed to evaluate the antimicrobial activity of 2-phenylethynyl
butyltellurium (PEBT) in Escherichia coli and the relation to its pro-oxidant
effect. For this, we carried out disk diffusion test, minimum inhibitory
concentration (MIC) assay, and survival curve analysis. We also measured the
level of extracellular reactive oxygen species (ROS), activity of the antioxidant
enzymes superoxide dismutase (SOD) and catalase (CAT), and level of non-protein
thiols (NPSH). PEBT at 1.28 and 0.128 mg/disk exhibited antimicrobial capability
in the disk diffusion test, with an MIC value of 1.92 mg/ml, whereas PEBT at
0.96, 1.92, and 3.84mg/ml inhibited bacterial growth after a 9-h exposure. PEBT
at 3.84, 1.92, and 0.96 mg/ml increased extracellular ROS production, decreased
the intracellular NPSH level, and reduced the SOD and CAT activities. Glutathione
or ascorbic acid in the medium protected the bacterial cells from the
antimicrobial effect of PEBT. In conclusion, PEBT exhibited antimicrobial
activity against E. coli, involving the generation of ROS, oxidation of NPSH, and
reduction of the antioxidant defenses in the bacterial cells.
PMID- 29943557
TI - Clinical Implication of Sarcopenia in Patients with Inflammatory Bowel Disease.
AB - Recent studies have shown that inflammatory bowel disease (IBD) patients are
affected by altered body composition, especially low muscle mass or sarcopenia.
Detection of sarcopenia is important, as it can independently predict osteopenia,
sarcopenic obesity, and poor disease outcomes during IBD progress. The challenges
are needed to identify diagnostic and managing strategies for sarcopenia in IBD
to improve disease outcomes and increase the quality of life in patients with
IBD.
PMID- 29943558
TI - Efficacy of Peracetic Acid (EndoPA(r)) for Disinfection of Endoscopes.
AB - Background/Aims: We aimed to investigate the efficacy of peracetic acid
(EndoPA(r) Firson Co., Ltd., Cheonan, Korea) in disinfecting endoscopes. Methods:
We prospectively investigated the gastroscopes (Part I) utilized in 100
gastroscopic examinations and colonoscopes (Part II) utilized in 30 colonoscopic
examinations after disinfecting them with 0.2% peracetic acid (EndoPA(r) Firson
Co., Ltd.). These instruments had been collected consecutively throughout the
study period. We reprocessed and disinfected the endoscopes according to the
guidelines for cleaning and disinfecting gastrointestinal endoscopes laid down by
the Korean Society of Gastrointestinal Endoscopy in 2017. Three culture samples
were obtained from each examination, based on different sampling methods. The
primary outcome was a positive culture rate. Results: In Part I of our study, two
of 300 samples were positive. The culture positive rate after disinfection was
0.7% (2/300). The culture positive rate was not significantly different based on
the exposure time to EndoPA(r) or the age of the scopes (p=0.7 or 0.2,
respectively). In Part II of our study, all samples (n=90) were negative.
Conclusions: We conclude that 0.2% peracetic acid (EndoPA(r)) appears to be a
good disinfectant for both gastroscopes and colonoscopes.
PMID- 29943559
TI - Gastrointestinal Gas and Abdominal Fat Quantity Measured by Three-Dimensional
Abdominal Computed Tomography in Patients with Functional Bloating.
AB - Background/Aims: The aim of this study was to assess whether increased intestinal
gas or fat content in the abdominal cavity is related to abdominal bloating,
using three-dimensional abdominal computed tomography scan. Methods: Twenty-nine
healthy individuals without abdominal bloating and organic disease (15 women;
mean age, 49 years; range of age, 23-73 years) and 30 patients with chronic
recurrent abdominal bloating-diagnosed with functional bloating (10 women; mean
age, 53 years; range of age, 35-75 years) - participated in this study. The mean
values of measured parameters were compared using independent sample t-test.
Results: The mean volume of total colon gas in bloated patients was similar to
that in control subjects. The distribution of intra-abdominal gas was also
similar between the two groups. However, the amount of gas in the transverse
colon tended to be significantly higher in patients with bloating than in
controls (p=0.06). Body mass index was similar between the two groups (23.4+/-3.2
kg/m2 and 22.3+/-3.1 kg/m2, respectively). Moreover, no significant differences
with respect to circumferential area, subcutaneous fat, visceral fat area, and
total fat area were found between the two groups. Conclusions: Bloating might not
just be the result of gastrointestinal gas or intra-abdominal fat. Other
contributing factors, such as localized abnormality in gas distribution and
visceral hypersensitivity, may be involved.
PMID- 29943560
TI - Diagnostic Value of Carcinoembryonic Antigen in Ascites for Colorectal Cancer
with Peritoneal Carcinomatosis.
AB - Background/Aims: Diagnostic tests for carcinoembryonic antigen (CEA) in ascites
have been performed in various malignant cases, but there is only few data on the
applicability of CEA for colorectal cancer (CRC) patients with peritoneal
carcinomatosis. We aimed to determine the usefulness of CEA in ascites (aCEA) as
a diagnostic parameter for CRC with peritoneal carcinomatosis. Methods: Between
January 2000 and May 2013, the medical records of 259 patients who underwent
paracentesis for the evaluation of ascites were retrospectively reviewed. CRC
patients with ascites (n=82) and patients with non-malignant ascites (n=177) were
evaluated. Patients who had other malignancies, including gastric or ovarian
cancer, with ascites were excluded. The optimal diagnostic cut-off value of aCEA
for CRC with peritoneal carcinomatosis was determined using receiver operating
characteristic curve analysis. The value of aCEA for predicting the occurrence of
peritoneal carcinomatosis was evaluated using a logistic regression model.
Results: The optimal cut-off value of aCEA to diagnose CRC with peritoneal
carcinomatosis was 3.89 ng/mL, and the area under the curve for aCEA was 0.996
(sensitivity 96.3%, specificity 100%, positive predictive value 100%, negative
predictive value 98.3%). Multivariate logistic regression analysis showed that
aCEA was an independent factor predicting the occurrence of peritoneal
carcinomatosis. Conclusions: In this study, we showed that aCEA may be a useful
parameter for diagnosing CRC with peritoneal carcinomatosis, and we propose an
optimal aCEA cut-off value of 3.89 ng/mL. Further study that includes patients
with other malignant ascites may be necessary to validate these findings.
PMID- 29943561
TI - Gastrointestinal cancer risk in patients with a family history of
gastrointestinal cancer.
AB - Background/Aims: This study was performed to evaluate the relationship between
family history of gastrointestinal (GI) cancers and incidence of any GI cancer in
the Korean population. Methods: Between January 2015 and July 2016, 711 GI cancer
patients and 849 controls in 16 hospitals in Korea were enrolled. Personal
medical histories, life styles, and family history of GI cancers were collected
via questionnaire. Results: There was a significant difference in the incidence
of family history of GI cancer between GI cancer patients and controls (p=0.002).
Patients with family history of GI cancer tended to be diagnosed as GI cancer at
younger age than those without family history (p=0.016). The family members of GI
cancer patients who were diagnosed before 50 years of age were more frequently
diagnosed as GI cancer before the age of 50 years (p=0.017). After adjusting for
major confounding factors, age (adjusted odds ratio [AOR] 1.065, 95% confidence
interval [CI]; 1.053-1.076), male gender (AOR 2.270, 95% CI; 1.618-3.184),
smoking (AOR 1.570, 95% CI; 1.130-2.182), and sibling's history of GI cancer (AOR
1.973, 95% CI; 1.246-3.126) remained independently associated with GI cancers.
Conclusions: GI cancer patients tended to have a first relative with a history of
concordant GI cancer. Personal factors (old age and male) and lifestyle (smoking)
contribute to the development of GI cancer, independently. Individuals with high
risk for GI cancers may be advised to undergo screening at an earlier age.
PMID- 29943562
TI - Case of Bleeding Ileal Varices after a Colectomy Diagnosed by Capsule Endoscopy.
AB - We report a case of bleeding ileal varices associated with intra-abdominal
adhesions after colectomy which was successfully diagnosed using capsule
endoscopy. A 77-year-old woman visited the emergency department for several
episodes of melena. She had a medical history of neoadjuvant chemo-radiation
therapy and subsequent surgery for rectal cancer 6 years previously. Conventional
diagnostic examinations including upper endoscopy, colonoscopy, and abdominal
computed tomography could not detect any bleeding focus, however, following
capsule endoscopy revealed venous dilatations with some fresh blood in the distal
ileum, indicating bleeding ileal varices. The patient underwent exploratory
laparotomy and the affected ileum was successfully resected. No further
gastrointestinal bleeding occurred during the 6 months follow-up. Small
intestinal varices are important differential for obscure gastrointestinal
bleeding especially in patients with a history of abdominal surgery in the
absence of liver cirrhosis, and capsule endoscopy can be a good option for
diagnosing small intestinal varices.
PMID- 29943563
TI - A Case of Graves' Disease Accompanied with Acute Hepatitis A Virus Infection.
AB - Concurrent presentation of acute hepatitis A virus (HAV) infection and Graves'
disease has not been reported in literature worldwide. Although there is no well
established mechanism that explains the induction of Graves' disease by HAV to
date, our case suggests that HAV infection may be responsible for inducing
Graves' disease. A healthy 27-year-old female presented fever, palpitation, and
diarrhea, and she was subsequently diagnosed as acute HAV infection.
Concurrently, she showed hyperthyroidism, and the diagnosis was made as Graves'
disease. She had never had symptoms that suggested hyperthyroidism, and previous
thyroid function test was normal. Acute HAV infection was recovered by
conservative management, however, thyroid dysfunction was maintained even after
normalization of liver enzymes. Methimazole was used to treat Graves' disease. We
report a case of concurrent acute HAV infection and Graves' disease in a patient
without preexisting thyroid disease. This suggests that HAV infection may be a
trigger for an autoimmune thyroid disease in susceptible individuals.
PMID- 29943564
TI - [Studies in the fauna of waters in the Polish part of the Tatra Mountains in the
years 1919-1939].
AB - This work constitutes a continued presentation of the history of Polish research
in the fauna of the Tatra waters and covers the inter-war period. During the
years 1919-1939 these studies were still conducted but on a smaller scale than
before the 1st World War. Many publications were based on earlier research done
before 1914, which were broader works concerning the territory of the whole
country, including also the Tatra waters, such as a monograph on the leeches of
Poland by Michal Giedroyc, lacewing insects by Jozef Dziegielewicz, or
juxtaposition of Heteroptera (true bugs) of "Galicia" by Adam Krasucki. Alfred
Litynski summed up his many years' research on the fauna of Cladocera (water
fleas) conducted in 120 ponds, both on the Polish and Slovak sides of the Tatra
Mountains. Unpublished materials of deceased scientists were used as well.
Professor Kazimierz Simm, the disciple of professor Antoni Wierzejewski who died
in 1916, published his monograph on Spongaria, in which he mentioned Spongaria
from the Toporowy Pond and included notes about the winter fauna in the outflow
of Morskie Oko. Museum collections were also used. Edward Schechtel worked out
feed for trouts caught in Morskie Oko in 1900. New research on the fauna of the
Tatra Mountains were conducted both as part of broader studies in the Polish
fauna but also presented results of studies pursued only in the Tatras. Numerous
researchers continued earlier studies of zooplankton crustacea in the waters of
the Tatra Mountains during the inter-war period. Monographic study on Phyllopoda
and Copepoda complexes of the Toporowy Pond was presented by Kazimierz Gajl.
Several works of Zygmunt Kozminski were devoted to population and taxonomic
studies on plankton crustacean Cyclops strennus. Tadeusz Wolski found in the bog
spring on Kalatowki a new Tatra species of water flea (Cladocera) - Moina
rectirostris. Meaningful from the scientific point of view and, at the same time,
controversial, was the work of Gajl on Branchinecta paludosa. Using an enormous
amount of materials coming from the Dwoisty Pond, as well as comparative material
from Scandinavia, arctic European and Asian parts of Russia, Greenland, Alasca,
and on the basis of differences in anatomical features, he came to a conclusion
that the population of the Polish Tatras was a separate species Branchinecta
polonica. This distinction was questioned later by scientists. It remained
unsolved, however, because the population of this species in the Dwoisty Pond
died out. At that time, for much broader scale studies were performed on
flatworms (Dendrocoelum lacteum). They were started by Wladyslaw Polinski with
his monograph on the distribution of two species of Acoela - Crenobia alpina i
Dugesia gonocephala - in Poland, and continued by W. Tomaszewski. Yet much
greater achievements in learning about this group were made by Marian Gieysztor,
who not only named several new species from the Tatras but on the basis of the
materials coming from there also described species quite new to science:
Macrostomum catarractae and Dalyellia tatrica. His research were on the global
scale and later scientists named one species Gieysztor. From the world-science
point of view, equally important were studies conducted by Witold Stefanski on
nematodes living freely in pond mosses and the lakes of the Tatra Mountains. In
addition to the register of species, majority of which were found for the first
time in the Tatra waters, he described three species new to science: Tripyla
tatrica, Steratocephalus demani and Bunonema steineri. One of the greatest
achievements of inter-war hydrobiology were studies concerning biology of the
inshore sands, the so-called psammon, conducted by Jerzy Wisniewski all over
Poland, including the territory of the Tatra Mountains. In the Tatras Wisniewski
studied the fauna of rotifers occurring in the psammon on the shores of lakes and
streams and the fauna of underwater sand. Briofile rotifers in Poland were
studied by Leszek Kazimierz Pawlowski and in his research materials from the
Tatra Mountains were also included. Similarly, Wladyslaw Rydzewski in his review
of Polish water mites from the Tatras named 9 species. On a smaller scale studies
were conducted on the insects living in the Tatra waters. In his key to mayflies,
based on the archive materials, Jozef Stanislaw Mikulski listed 7 species from
the Tatra Mountains. A note on morphologic differences of mayflies from Baetis
alpinus group was published by Anna Steinberg. Publishing his findings of many
years' studies on lacewings in Poland from the area of the Tatra Mountains, Jan
Zacwilichowski named only one species Sialis flavilateratafrom Stawy
Gasiennicowe. In a thorough monograph by Tadeusz Jaczewski on water boatmen
(Heteroptera) in Poland, there is only one mention of aquatic bug Glaenocorisa
cavifrons occurring in the Toporowy Staw. In his subsequent work (Jaczewski),
another species from Toporowy Staw was mentioned - Notonecta lutea. Of
fundamental importance were only the studies on Tatra dragonflies conducted by
Jozef Fudakowski. He found 39 species of dragonflies in the area of the Tatra
Mountains, occurring in lower water bodies: Toporowy Staw Nizny, Toporowy Staw
Wyzny, Smreczynski Staw, at Capki bog-spring, on Siwa Polana, in Dolina
Kondratowa, Dolina Pyszna, and the high-situated bog-spring near Morskie Oko. A
popular-science review of studies on the Tatra lakes, which included also fauna
research, were presented by Jerzy Mlodziejowski i J. Rzoska.
PMID- 29943565
TI - [Edward Forbes (1815-1854). A creationist who contributed to the development of
evolutionism].
AB - Charles Darwin's On the Origin of Species appeared in bookshops in 1859. The
history of the publication has been discussed in many publications. It is often
stressed that Darwin had decided to publish the theory after reading a letter
from Alfred Russel Wallace, who independently drew similar conclusion. However,
in a detailed investigation into the history of evolutionism, contribution of
Edward Forbesto making the theory public should also be acknowledged. This less
known to the contemporaries British naturalist had died (at the age of 39) before
Darwin's opus magnum was published. Forbes' premature death was considered a
great tragedy for the world of natural science. He was a creationist and stated
that the paleontological data unambiguously indicate that the new species are not
the result of transmutation but are God's creation. The aim of this publication
is to present Forbes' contribution to the development of the theory publically
criticized by him.
PMID- 29943566
TI - [Anatomy in the perspective of Kazimierz Kostanecki].
AB - Kazimierz Telesfor Kostanecki (1863-1940) remains one of the most important
figures in the history of Polish medicine and natural science. He was the creator
of one of the biggest scientific schools on Polish soil, a researcher versatile,
working in parallel on many fields of natural science exploration. In his view,
anatomy has become a dynamic and comprehensive science, that combines what today
belongs to histology, cytology and embryology. Kostanecki has created an
universal model of research, referring to comparative methods and based on
planned series of experimental studies, especially when it came to issues related
to developmental anatomy and mechanics of fertilization. This model was used and
developed by his students and followers. It is not surprising, therefore, that
the name Kostanecki has been repeatedly reported in the world literature, and a
number of phenomena and facts established by him has kept its value, which comes
obviouswhen we still can find citations of Polish scholar works in the
contemporary monographs and articles.
PMID- 29943567
TI - A Chiral Organic Field-Effect Transistor with a Cyclodextrin Modulated Copper
Hexadecafluorophthalocyanine Semiconductive Layer as the Sensing Unit.
AB - This work reported the construction of a chiral sensor based on an organic field
effect transistor to probe the subtle change of weak interactions in the chiral
discrimination process, with the ability to achieve fast, sensitive, and
quantitative real-time chiral analysis for various racemic pairs, where a beta
cyclodextrin (beta-CD) sensitized copper hexadecafluorophthalocyanine (F16CuPc)
semiconductive layer was employed as the sensing unit. Physical adsorptive
assembly of beta-CD on the semiconductive layer guarantees the impressive field
effect-amplified chiral sensitivity. The enantiomer induced aggregation pattern
diversification of the sensing layer resulted in enhanced or weakened surface
dipole interactions to various degrees and hence brought about the drain current
fluctuation. A fast and real-time detection of the enantiomer pairs in aqueous
solution at 10-9 M was achieved. This chiral organic field-effect transistor
(COFET) afforded reliable ability for quantitative determination of the pure
isomer content in enantiomer pairs and was further proven to have great potential
for the resolution of "real-world" pharmaceutical drugs.
PMID- 29943568
TI - Asymmetric Syntheses of (2 R,3 S)-3-Hydroxyproline and (2 S,3 S)-3
Hydroxyproline.
AB - Two synthetic routes have been developed for the asymmetric syntheses of (2 R,3
S)- and (2 S,3 S)-3-hydroxyproline. The key synthetic step in each of these
strategies is the conversion of protected alpha,delta-dihydroxy-beta-amino esters
(either 2,3- anti- or 2,3- syn-configured) into beta,delta-dihydroxy-alpha-amino
esters (protected forms thereof), via the intermediacy of the corresponding
aziridinium ions. The products of these stereospecific rearrangements were then
cyclized and deprotected to afford (2 R,3 S)-3-hydroxyproline and (2 S,3 S)-3
hydroxyproline as single diastereoisomers (>99:1 dr) in >26% overall yield.
PMID- 29943569
TI - Evidence of Influence of Human Activities and Volcanic Eruptions on Environmental
Perchlorate from a 300-Year Greenland Ice Core Record.
AB - A 300-year (1700-2007) chronological record of environmental perchlorate,
reconstructed from high-resolution analysis of a central Greenland ice core,
shows that perchlorate levels in the post-1980 atm were two-to-three times those
of the pre-1980 environment. While this confirms recent reports of increased
perchlorate in Arctic snow since 1980 compared with the levels for the prior
decades (1930-1980), the longer Greenland record demonstrates that the Industrial
Revolution and other human activities, which emitted large quantities of
pollutants and contaminants, did not significantly impact environmental
perchlorate, as perchlorate levels remained stable throughout the 18th, 19th, and
much of the 20th centuries. The increased levels since 1980 likely result from
enhanced atmospheric perchlorate production, rather than from direct release from
perchlorate manufacturing and applications. The enhancement is probably
influenced by the emission of organic chlorine compounds in the last several
decades. Prior to 1980, no significant long-term temporal trends in perchlorate
concentration are observed. Brief (a few years) high-concentration episodes
appear frequently over an apparently stable and low background (~1 ng kg-1).
Several such episodes coincide in time with large explosive volcanic eruptions
including the 1912 Novarupta/Katmai eruption in Alaska. It appears that
atmospheric perchlorate production is impacted by large eruptions in both high-
and low-latitudes, but not by small eruptions and nonexplosive degassing.
PMID- 29943570
TI - Regioselective Copper-Catalyzed Oxidative Coupling of alpha-Alkylated Styrenes
with Tertiary Alkyl Radicals.
AB - A radical-mediated oxidative cross-coupling of readily accessible alpha-alkylated
styrenes with 1,3-dicarbonyl compounds utilizing a combination of Cu(OAc)2 and
air as a catalytic system is described. Rather than requiring alpha-halocarbonyl
compounds, this efficient approach enables direct installation of tertiary
functionalized alkyl motifs to olefins with simple carbonyl derivatives. The
novel protocol is characterized with high allylic selectivities via a competing
beta-H elimination. Both radical-clock and -trapping experiments provided clear
cut evidence for the intermediacy of an alpha-keto carbon-centered radical.
PMID- 29943571
TI - A Re-examination of the Synthesis of Monolayer-Protected Co x(SCH2CH2Ph) m
Nanoclusters: Unexpected Formation of a Thiolate-Protected Co(II) T3
Supertetrahedron.
AB - Herein, we report a re-examination of the synthesis and characterization of
monolayer-protected Co x(SCH2CH2Ph) m nanoclusters. These clusters were
reportedly formed by the reaction of CoCl2 with NaBH4 in the presence of
HSCH2CH2Ph and were suggested to contain between 25 and 30 Co atoms. In our
hands, however, we found no experimental evidence to support the existence of
these large clusters in the reaction mixture. Instead, this reaction results in
the relatively clean formation of the cobalt(II) coordination complex
[Co10(SCH2CH2Ph)16Cl4] (1). Complex 1 has been fully characterized using a wide
variety of techniques, including single-crystal X-ray crystallography, NMR
spectroscopy, mass spectrometry, and magnetometry. This complex represents the
first example of a thiolate-protected Co(II) T3 supertetrahedral cluster.
PMID- 29943572
TI - Simultaneous Improvement of Efficiency and Lifetime of Quantum Dot Light-Emitting
Diodes with a Bilayer Hole Injection Layer Consisting of PEDOT:PSS and Solution
Processed WO3.
AB - Even though chemically stable metal oxides (MOs), as substitutes for poly(3,4
ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), have been successfully
adopted for improving device stability in solution-processed quantum dot light
emitting diodes (QLEDs), the efficiencies of QLEDs are at a relatively low level.
In this work, a novel architecture of QLEDs has been introduced, in which
inorganic/organic bilayer hole injection layers (HILs) were delicately designed
by inserting an amorphous WO3 interlayer between PEDOT:PSS and the indium tin
oxide anode. As a result, the efficiency and operational lifetime of QLEDs were
improved simultaneously. The results show that the novel architecture QLEDs
relative to conventional PEDOT:PSS-based QLEDs have an enhanced external quantum
efficiency by a factor of 50%, increasing from 8.31 to 12.47%, meanwhile exhibit
a relatively long operational lifetime (12 551 h) and high maximum brightness
(>40 000 cd m-2) resulting from a better pathway for hole injection with
staircase energy-level alignment of the HILs and reduction of surface roughness.
Our results demonstrate that the novel architecture QLEDs using bilayer
MO/PEDOT:PSS HILs can achieve long operational lifetime without sacrificing
efficiency.
PMID- 29943573
TI - Paper-Based Enzyme Competition Assay for Detecting Falsified beta-Lactam
Antibiotics.
AB - Falsified and substandard antibiotics are a growing worldwide problem that leads
to increased patient mortality and decreased trust in healthcare, and contributes
to antimicrobial resistance. Monitoring falsified antibiotics is difficult
because most falsified pharmaceuticals are most commonly found in developing
countries, where detecting the active ingredient is difficult due to lack of
access to complex instrumentation. Herein, we describe the development and
optimization of a microfluidic paper-based analytical device (MUPAD) to detect
the active ingredient in the most falsified class of antibiotics, beta-lactams.
The assay is based on enzyme competition, making it the first demonstrated
competitive enzyme assay reported in paper-based devices. The assay uses
nitrocefin, a chromogenic substrate, to compete with beta-lactam antibiotics in a
reaction with beta-lactamase. A yellow color indicates legitimate drugs, while a
color change from yellow to red indicates falsified drugs. In addition to testing
for the active ingredient, another section of the device was added to test the
sample pH to further verify results and identify common falsified ingredients
like aspirin or baking soda. Calibration curves for four different antibiotics,
including cefazolin, have been generated making it the first paper-based device
capable of detecting both cephalosporin and penicillin antibiotics. The MUPAD has
also been tested with common falsified ingredients and four antibiotics in tablet
or injectable form, demonstrating its potential for in-field falsified antibiotic
testing.
PMID- 29943574
TI - Versatile Exciplex-Forming Co-Host for Improving Efficiency and Lifetime of
Fluorescent and Phosphorescent Organic Light-Emitting Diodes.
AB - We report a new efficient exciplex-forming system consisting of a biscarbazole
donor and a triazine-based acceptor. The new exciplex was characterized with a
high photoluminescence quantum yield up to 68% and effective thermally activated
delayed fluorescence behavior. The BCzPh:3P-T2T (2:1, 30 nm) blend was examined
not only as an emitting layer (device D1) but also a reliable co-host of
fluorescent and phosphorescent emitters for giving highly efficient exciplex
based organic light-emitting diodes (OLEDs) with a high maximum external quantum
efficiency of 15.5 and 29.7% for devices doped with 1 wt % C545T (device D2) and
8 wt % Ir(ppy)2(acac) (device D4), respectively. More strikingly, a strongly
enhanced lifetime ( T75 = 16 927 min.) of the C545T-doped device was obtained.
The transient electroluminescence measurement as well as capacitance-voltage and
impedance-voltage correlations were utilized to explore the factors governing the
high efficiency and stability. The obtained results clearly show that the energy
transfer and charge transport is highly efficient; they also show the
photoelectric semiconducting characteristics of exciplex-based OLEDs, which are
significantly different from those of unipolar host-based reference devices D3
(Alq3: 1 wt % C545T) and D5 (CBP: 8 wt % Ir(ppy)2(acac)). Our works have
established a systematic protocol to shed light on the mechanisms behind exciplex
based devices. The combined results also confirm the bright prospect of the
exciplex-forming system as the co-host for highly efficient and stable OLEDs.
PMID- 29943575
TI - Portable Aptasensor of Aflatoxin B1 in Bread Based on a Personal Glucose Meter
and DNA Walking Machine.
AB - Despite some recent developments on the portable on-site sensor of Aflatoxin B1
(AFB1), the complex and expensive preparation of recognition elements have still
limited their wide applications. In this paper, using the fast, low-cost, and
stable recognition of aptamer DNA-AFB1, a portable aptasensor was constructed for
the on-site detection of AFB1 in food matrixes, with the readout of personal
glucose meter (PGM) and DNA walking machine for signal probe separation. In such
an assay protocol, the target could trigger the DNA walker to autonomously move
on the electrode surface, propelled by unidirectional Pb2+-specific DNAzyme
digestion, which could amplify the signal and separate the signal probe as well
for further quantification by the PGM. Under optimized conditions, the increase
of PGM signal was relative with the concentration of AFB1 ranging from 0.02 to 10
nM and the low limit of detection (LOD) was 10 pM (S/N = 3). With the features of
portability, and cheapness, the presented user-friendly method could be extended
to various other analytes for wide point-of-care applications.
PMID- 29943576
TI - Phase Stability and Electronic Structure of Prospective Sb-Based Mixed Sulfide
and Iodide 3D Perovskite (CH3NH3)SbSI2.
AB - Lead-free antimony-based mixed sulfide and iodide perovskite phases have recently
been reported to be synthesized experimentally and to exhibit reasonable
photovoltaic performance. Through a combination of experimental validation and
computational analysis, we show no evidence of the formation of the mixed sulfide
and iodide perovskite phase, MASbSI2 (MA = CH3NH3+), and instead that the main
products are a mixture of the binary and ternary compounds (Sb2S3 and MA3Sb2I9).
Density functional theory calculations also indicate that such a mixed sulfide
and iodide perovskite phase should be thermodynamically less stable compared with
binary/ternary anion-segregated secondary phases and less likely to be
synthesized under equilibrium conditions. Additionally, band structure
calculations show that this mixed sulfide and iodide phase, if possible to
synthesize (e.g., under nonequilibrium conditions), should have a suitable direct
band gap for photovoltaic application.
PMID- 29943577
TI - Thin and Flexible Carbon Nanotube-Based Pressure Sensors with Ultrawide Sensing
Range.
AB - A scalable electrophoretic deposition (EPD) approach is used to create novel
thin, flexible, and lightweight carbon nanotube-based textile pressure sensors.
The pressure sensors can be produced using an extensive variety of natural and
synthetic fibers. These piezoresistive sensors are sensitive to pressures ranging
from the tactile range (<10 kPa), the body weight range (~500 kPa), and very high
pressures (~40 MPa). The EPD technique enables the creation of a uniform carbon
nanotube-based nanocomposite coating, in the range of 250-750 nm thick, of
polyethyleneimine (PEI) functionalized carbon nanotubes on nonconductive fibers.
In this work, nonwoven aramid fibers are coated by EPD onto a backing electrode
followed by film formation onto the fibers creating a conductive network. The
electrically conductive nanocomposite coating is firmly bonded to the fiber
surface and shows piezoresistive electrical/mechanical coupling. The pressure
sensor displays a large in-plane change in electrical conductivity with applied
out-of-plane pressure. In-plane conductivity change results from fiber/fiber
contact as well as the formation of a sponge-like piezoresistive nanocomposite
"interphase" between the fibers. The resilience of the nanocomposite interphase
enables sensing of high pressures without permanent changes to the sensor
response, showing high repeatability.
PMID- 29943578
TI - RNA Environment Is Responsible for Decreased Photostability of Uracil.
AB - UV light can induce chemical reactions in nucleic acids and thereby damage the
genetic code. Like all of the five primary nucleobases, the isolated RNA base
uracil exhibits ultrafast, nonradiative relaxation after photoexcitation, which
helps to avoid photodamage most of the time. Nevertheless, within RNA and DNA
strands, commonly occurring photolesions have been reported and are often
ascribed to long-lived and delocalized excited states. Our quantum dynamical
study now shows that excited-state longevity can also occur on a single
nucleobase, without the need for delocalization. We include the effects of an
atomistic RNA surrounding in wave packet simulations and explore the
photorelaxation of uracil in its native biological environment. This reveals that
steric hindrance through embedding in an RNA strand can inhibit the ultrafast
relaxation mechanism of uracil, promoting excited-state longevity and potential
photodamage. This process is nearly independent from the specific combination of
neighboring bases.
PMID- 29943579
TI - Designing Stability into Thermally Reactive Plumbylenes.
AB - Lead analogues of N-heterocyclic carbenes (NHPbs) are the least understood
members of this increasingly important class of compounds. Here we report the
design, preparation, isolation, structure, volatility, and decomposition pathways
of a novel aliphatic NHPb: rac- N 2, N 3-di- tert-butylbutane-2,3-diamido
lead(II) (1Pb). The large steric bulk of the tert-butylamido moieties and rac
butane backbone successfully hinder redox decomposition pathways observed for
diamidoethylene and -ethane backbone analogues, pushing the onset of thermal
decomposition from below 0 degrees C to above 150 degrees C. With an
exceptionally high vapor pressure of 1 Torr at 94 +/- 2 degrees C and excellent
thermal stability among Pb(II) complexes, 1Pb is a promising precursor for the
chemical vapor deposition (CVD) and atomic layer deposition (ALD) of functional
lead-containing materials.
PMID- 29943580
TI - Nickel-Catalyzed Arylative Carboxylation of Alkynes with Arylmagnesium Reagents
and Carbon Dioxide Leading to Trisubstituted Acrylic Acids.
AB - Nickel-catalyzed arylcarboxylation of alkynes with arylmagnesium reagents and
carbon dioxide (CO2, 1 atm) was realized in one pot. Various trisubstituted
acrylic acids within an aryl group at the beta-position have been prepared
efficiently with good regioselectivity under mild conditions. The resulting
products could be further transformed to benzoannelated cycles retaining CO2 as a
one-carbon synthon.
PMID- 29943581
TI - Comparing clinical effects of marbofloxacin and gamithromycin in goat kids with
pneumonia.
AB - The aim of this study was to compare the clinical efficacy of a single-dose of
gamithromycin (GM) or marbofloxacin (MR) in kids with naturally occurring
pneumonia. Thirty-six kids, aged 2-2.5 months, with body weight ranging from 12
kg to 18 kg were presented with clinical signs of pneumonia. The most prominent
clinical findings were an increase in the respiratory rate, crackling lung sounds
on auscultation, coughing, nasal discharge and an increased rectal temperature.
Mannheimia haemolytica and Mycoplasma spp. colonies were isolated from
microbiological examination of six transtracheal washes and lung tissues of one
necropsied kid. The severity of pneumonia was evaluated by using cumulative
clinical score (CCS). The CCS of the 36 kids used in the study were four and
above. Kids were randomly divided into two equal groups; the GM group received a
single subcutaneous dose of GM at a dosage of 6 mg/kg and the MR group received
MR intramuscularly at a dosage of 8 mg/kg as a single-dose. No side effects
related to the drugs were detected in either group. All 36 kids were clinically
examined 3 weeks after the initiation of the treatment. Clinical signs in both
groups were almost completely absent at the end of the study. A single
administration of GM or MR was successfully used in the treatment of kids with
pneumonia.
PMID- 29943582
TI - A model to facilitate the mental health of psychiatric nurses in a forensic unit
to manage mental health care users' hostile behaviour constructively.
AB - BACKGROUND: Hostile behaviour by mental health care users (MHCUs) is prevalent
in forensic units in South Africa, and this causes service providers distress and
burnout. Psychiatric nurses (PNs) find it difficult to render quality care to
MHCUs who are threatening them and also challenging their authority in a forensic
unit. Forensic mental health care practitioners may be challenged to engage
authentically with MHCUs who constitute a risk to their personal safety or who
have committed acts the practitioner finds morally disturbing. There is a need to
facilitate the mental health of PNs in a forensic unit to manage hostile
behaviour constructively. OBJECTIVE: The objective of this article is to
describe the process that was followed in developing, implementing and evaluating
a model that could be used as a framework of reference to facilitate the mental
health of PNs in a forensic unit to manage hostile behaviour constructively.
METHOD: A theory-generative, qualitative, exploratory descriptive and contextual
study design was used to develop the model. The steps of the process entailed the
identification of the central concept, the definition of the central concept and
other essential criteria and the classification of the central and related
concepts. The model was then described and evaluated. RESULTS: The central
concept was identified as the 'facilitation of empowerment of PNs to manage
hostility in a constructive manner', defined, classified and then described and
evaluated. CONCLUSION: The model as framework of reference could assist PNs in
managing hostility in a forensic unit constructively.
PMID- 29943583
TI - Occurrence of the specific long spike burst pattern in the ovine proximal
gallbladder as an indication of myoelectric regional variability.
AB - The myoelectrical activity of the ovine gallbladder has not been fully
recognised. Five rams were fitted with six small intestinal and three gallbladder
electrodes and a strain gauge force transducer was mounted near the gallbladder
fundic electrode. In two series of successive experiments, the
electromyographical and mechanical recordings were recorded over a period of 5-7
hours. The occurrence of the slow waves in the small bowel was regular, unlike
those in the gallbladder. In the gallbladder infundibulum, the specific pattern,
called the long spike burst pattern (LSBP), was observed. It comprised usually
one or two parts of prolonged duration. The first part resembled the classical
(short lasting) spike burst in the small bowel, and its amplitude was lower than
that of the second part. The spike burst frequency of the second part was 2-3
times lower than that of the first part. During phase 1-like and phase 2a-like
activities, the intensity of the gallbladder LSBP was reduced while enhanced
after feeding. In fasted rams, the duration of a specific pattern, observed in
the gallbladder infundibulum, was longer than in non-fasted animals and its
amplitude was low. Similar events were recorded in the gallbladder corpus, but
the specific pattern was shorter and irregular. In the gallbladder fundus, mostly
irregular short spike bursts were recorded. It is concluded that in sheep,
specific types of the long-lasting groups of spikes occur in the upper
gallbladder areas exhibiting myoelectrical regional variability. The character of
an LSBP depends on feeding conditions.
PMID- 29943584
TI - Prevalence of mastitis pathogens in South African pasture-based and total mixed
ration-based dairies during 2008 and 2013.
AB - Recent years have seen a change in the relative prevalence of environmental and
contagious intramammary pathogens, as well as a change in the relative number of
total mixed ration (TMR)-based and pasture (PAS)-based dairies in South Africa.
The objectives of the study were to determine and compare the prevalence of
mastitis pathogens in TMR and PAS dairies in South Africa during 2008 and 2013;
furthermore, the within-herd prevalence of Streptococcus uberis in Str. uberis
positive herds was determined and compared. The prevalence of each pathogen, as
well as the within-herd prevalence of Str. uberis, were compared between the two
years and the two management systems using bacterial culture results from
routinely collected composite cow milk samples submitted to the Onderstepoort
Milk Laboratory, Faculty of Veterinary Science, University of Pretoria. Coagulase
negative staphylococci had the highest prevalence in both TMR and PAS dairies for
both 2008 (29.60% [95.00% CI: 28.80% - 30.40%] and 26.90% [95.00% CI: 25.50% -
28.30%], respectively) and 2013 (20.20% [95.00% CI: 19.30% - 21.10%] and 22.70%
[95.00% CI: 22.20% - 23.10%], respectively), which decreased significantly from
2008 to 2013 in both TMR and PAS dairies (p < 0.001). Streptococcus uberis showed
an increase in prevalence in both TMR (p = 0.002) and PAS dairies (p = 0.001)
from 2008 (2.36% [95.00% CI: 2.10% - 2.65%] and 2.63% [95.00% CI: 2.16% - 3.16%],
respectively) to 2013 (3.10% [95.00% CI: 2.72% - 3.51%] and 3.64% [95.00% CI:
3.45% - 3.83%], respectively). Staphylococcus aureusshowed a significant decrease
in both TMR (p = 0.011) and PAS (p < 0.001) dairies from 2008 (4.71% [95.00% CI:
4.34% - 5.10%] and 5.62% [95.00% CI: 4.94% - 6.36%], respectively) to 2013 (3.95%
[95.00% CI: 3.52% - 4.40%] and 1.71% [95.00% CI: 1.58% - 1.84%], respectively).
The median within-herd prevalence of Str. uberis for the combined dairy systems
showed a significant increase from 2008 (1.72% [IQR: 0.88% - 5.00%]) to 2013
(3.10% [IQR: 1.72% - 4.70%]) (p < 0.001). Statistically significant differences
were found in the prevalence of most of the major contagious and environmental
mastitis pathogens between 2008 and 2013 and between TMR and PAS dairies. The
within-herd prevalence of Str. uberis increased from 2008 to 2013, with the
highest within-herd prevalence in PAS dairies in 2013.
PMID- 29943585
TI - A pilot study: Considering spirituality in an inclusive model of practice in
clinical audiology.
AB - BACKGROUND: A patient-orientated approach in medical clinical practice is
emerging where patients and practitioners are considering and including the
spiritual, emotional and psychosocial aspects of the individual. This practice is
an important change in health care, specifically in the field of audiology as a
holistic view of the patient now alters the perspective on the management of
individuals with hearing impairments. Objectives: This article explored the
experiences of a participant who reported supernatural healing of his
sensorineural hearing loss (SNHL). Hence, this study focuses on the consideration
of spirituality in the inclusive model of care. Method: An exploratory,
qualitative narrative inquiry was used to obtain data from a single pilot case
study of a 27-year-old man who reported healing of his permanent profound hearing
loss. Results: Four themes were identified within the narrative obtained: prayer
and faith, deaf culture, identity and purpose. The participant stated that he
believed that he was partially healed to fulfil his purpose in life. The partial
healing allowed him to belong to the deaf community and the hearing world
simultaneously. Conclusion: South Africans live in a diverse society where most
people accept spirituality as part of their search for meaning in life. Health
care for individuals should therefore consider the person as a holistic being
more than a medical entity. The exploration of narratives of individuals who
report supernatural healing of a SNHL will assist health care practitioners and
audiologists in managing individuals in an inclusive manner. This pilot study
thus has implications for policy and practice in health care contexts.
PMID- 29943586
TI - Erratum: Wideband acoustic immittance for assessing middle ear functioning for
preterm neonates in the neonatal intensive care unit.
AB - No abstract available.
PMID- 29943587
TI - Exploring the efficacy of melodic intonation therapy with Broca's aphasia in
Arabic.
AB - BACKGROUND: Even though the efficacy of melodic intonation therapy (MIT) with
persons with aphasia (PWA) has been explored in different languages, the efficacy
of MIT with Arabic-speaking PWA has never been explored. Aims: To explore the
efficacy of MIT, adapted to Arabic, in promoting the expressive abilities of a 70
year-old Jordanian Arabic-speaking male subject with severe Broca's aphasia 3
months post-onset. Methods: An 8-week MIT therapy programme with tapping (1.5 h
daily, 6 days a week) was used in a multiple baseline design across two types of
trained phrases (i.e. automatic and self-generated phrases). Outcome measures
included accuracy of production of trained (at the end of each session) and
untrained phrases (at the end of each week). Pre- and post-treatment measures
used, were the bilingual aphasia test, the American Speech-Language Hearing
Association Functional Assessment of Communicative Skills, the communicative
effectiveness index and the American Speech and Hearing Association Quality of
Communication Life Scale. Accuracy of production for the trained and untrained
phrases was also measured 2 weeks and 4 weeks after the treatment programme was
finished. Results: The patient, (MK), improved his expressive productions post
treatment in automatic and self-generated phrases. Automatic phrases exceeded the
established 75% accuracy criterion, whereas the self-generated phrases reached
criterion and remained constant at follow-up. Moreover, MK gradually started
improving on the generalisation stimuli, once the treatment on the self-generated
phrases started and maintained the gains 2 weeks and 4 weeks post-treatment.
Conclusion: MIT appears to be a viable treatment option for Jordanian Arabic
speaking persons with Broca's aphasia. However, more research is needed with
larger groups of Jordanian Arabic-speaking persons with Broca's aphasia to
provide more support to the present findings. Moreover, future studies might
focus on the efficacy of MIT with persons with Broca's aphasia from different
Arab countries and from countries where Arabic is part of the multicultural
structure like South Africa and other countries on the African continent.
PMID- 29943588
TI - Skydiving: The audiological perspective.
AB - BACKGROUND: Skydiving is a popular recreational sport for the young and old.
There is minimal research pertaining to skydiving and its relation to the
audiological system. The risks of skydiving in relation to the auditory system
should be explored further. Aims: The main aim of this study was to explore the
relationship between skydiving and audiology in South Africa. The sub-aims of the
study focused on determining if skydivers were provided with safety precautions
before they commenced with the dive, determining the middle ear pressure before
and after the skydive and identifying the audiological symptoms that were present
post-dive. This study also aimed at scrutinising the South African sports and
recreation policy. Method: A mixed-method descriptive research design was
utilised. Qualitative information pertaining to audiology was identified and
recorded from the scrutiny of South Africa (SA) policy and the dropzone consent
forms at two skydiving schools. Thirty-one skydivers were purposefully recruited
to undergo a pre- and post-dive tympanometric assessment. Results: There is no
information within the clearance forms that pertain to the audiological risks
related to skydiving. There was a lack of information related to the risks of
skydiving in the clearance forms at both dive schools. A statistically
significant pressure change was noted in regular skydivers, regardless of the
ability to equalise effectively during the skydive. Conclusion: This study
identified the gaps in policy and clearance forms, highlighting the need for the
inclusion of safety measures and risks in the documentation and legislation that
governs the sport. Audiologists, sportspeople and medical advisors should be
cognisant of the negative consequences that may be evident within the auditory
system of skydivers.
PMID- 29943589
TI - Priority areas for cannabis and cannabinoid product research in South Africa.
AB - No abstract available.
PMID- 29943590
TI - Delivery of primary health care in Malawi.
AB - Malawi is a landlocked country with a population of 17 million. The delivery of
the health care system is based on primary health care (PHC). The PHC structures
are acceptable; however, the system is marked by maldistribution of resources,
fragmentation of services and shortage of staff. This hampers the function of the
set, well-meaning PHC frameworks. Family medicine offers training and retention
of the PHC and rural workforce, harnessing clinical governance and capacity
building. Family medicine's role extends to involve advocacy for the PHC to
improve its performance.
PMID- 29943591
TI - Antiretroviral initiation of pregnant women and antenatal care booking practices
in eThekwini District, KwaZulu-Natal, South Africa.
AB - BACKGROUND: The introduction of antiretroviral therapy (ART) in South Africa
began as part of the prevention of mother-to-child transmission programme. For
significant reduction of vertical transmission, early antenatal care booking and
ART initiation are necessary. AIM: This study aimed to evaluate ART initiation
and booking practices of women attending antenatal care in eThekwini district
during financial years (FY) 2010/2011 and 2013/2014. METHODS: An observational
study used a retrospective chart review at four eThekwini district community
health centres (CHC). From these CHCs, records of women that initiated ART in
FY10/11 and FY13/14 were reviewed and compared for ART initiation delays and
booking practices. RESULTS: A total of 2749 pregnant women who attended antenatal
care (ANC) at the study sites were found eligible for ART; of these, 49% (n =
1334) attended ANC in FY10/11 while 51% (n = 1414) attended in FY13/14. In
FY10/11, 46% (n = 610) and 60 % (n = 855) of the womenwere initiated on ART
during pregnancy. The mean gestational age at booking for FY10/11 was 20.88
(standard deviation [s.d.] = 5.6) and 18.40 (s.d. = 6.2) in FY13/14. The mean
gestational age at ART initiation for women who initiated ART in FY10/11 was
26.30 (s.d. = 6.02) and in FY13/14 it was 19.06 (s.d. = 6.86). CONCLUSION: In
FY13/14 ART initiations occurred within 4 days after booking. ANC booking before
20 weeks was found to have improved between the two years from 39% to
58%;however, on average, in both years women booked during the second trimester.
PMID- 29943592
TI - Reasons for inconsistent condom use by young adults in Mahalapye, Botswana.
AB - BACKGROUND: Botswana is one of the countries significantly affected by the HIV
and AIDS epidemic. Despite an extensive preventive campaign, the incidence of HIV
remains high.Condoms are an important contributor to prevention of new HIV
infections, although they are not consistently used by young adults. AIM: The aim
of this study was to explore the reasons why condoms are not consistently usedby
young adults. SETTING: Mahalapye District Hospital and Airstrip Clinic, Botswana.
METHOD: This was a phenomenological qualitative study using individual in-depth
interviews.Eleven participants were purposively selected, including six males and
five females. Data were transcribed and analysed using the framework method.
RESULTS: All participants acknowledged the importance of utilising condoms to
prevent unplanned pregnancies and sexually transmitted infections. Reasons not to
use condoms were a need to have a child,implied lack of trust or faithfulness,
long-term relationships need toplease the partner and decreased pleasure. Other
contributing factors were lack of knowledge of benefits, less fear of contracting
HIV and AIDS as it can now be controlled with medication,influence of tradition,
alcohol and drug abuse, peer pressure, power and gender issues and the refusal of
the partner. The female condom was largely rejected by young adults in general
and by women in particular because of its size and the perception that it is
complicated to insert. CONCLUSION: The current preventive campaign against HIV
and AIDS needs to take cognisance of the factors affecting decisions on the use
of condoms by young adults and the obstacles to their use, particularly the new
belief that HIV and AIDS is no longer a significant concern.
PMID- 29943593
TI - Mental health in primary care: Integration through in-service training in a South
African rural clinic.
AB - BACKGROUND: Integrating mental health into primary care is a global priority. It
is proposed to 'task-share' the screening, diagnosis and treatment of common
mental disorders fromspecialists to primary care workers. Key to facilitating
this is training primary care workers to deliver mental health care. Mental
health training in Africa shows a predominance of short-term, externally driven
training programmes. Locally, a more sustainable delivery system was needed. AIM:
The aim of the study was to develop and evaluate a locally delivered, long-term,
inservice training programme to facilitate mental health care in primary care.
METHODS: This was a quasi-experimental study using mixed methods. The in-service
training programme was delivered in weekly 1-h sessions by local psychiatry staff
to 20 primary care nurses at the clinic over 5 months. The training was evaluated
using quantitative data from participant questionnaires and analysis of the
referrals from primary to specialist care. Qualitative data were collected via
semi-structured interviews and 14 observed training sessions. RESULTS: The
training was feasible and well received. Referrals to the mental health nurse
increased in quality and participants' self-rated competence improved. Additional
benefits included the development of supervision skills of mental health nurses
and providing a forum for staff to discuss service improvement. The programme
acted as a vehicle to pilot integration in one clinic and identify unanticipated
barriers prior to rollout. CONCLUSIONS: Long-term, in-service training, using
existing local staff had benefits to the integration of mental health into
primary care. This approach could be relevant to similar contexts elsewhere.
PMID- 29943594
TI - Knowledge of cervical cancer, human papillomavirus and prevention among first
year female students in residences at the University of the Free State.
AB - BACKGROUND: Cervical cancer is the second most common cancer among women in South
Africa. One of the major risk factors for the development of cervical cancer is
the human papillomavirus (HPV). AIM: To determine the knowledge of first-year
female students living in residences on the main campus of the University of the
Free State (UFS) regarding cervical cancer and HPV. SETTING: Female residences on
the main campus of UFS. METHODS: A descriptive cross-sectional study was
conducted on participants between the ages of 18 and 25 years using a non-random
convenience sampling method. Seven residences were included. Anonymous self
administered questionnaires were distributed during the eveningmeetings to all
first-year female students at the selected residences after an information
session.Students had to complete the questionnaires immediately after the
meeting. RESULTS: Most of the 373 respondents (85.8%) knew that cervical cancer
arises from the cervix, but only 15.4% knew that it was caused by a virus. Of the
62.5% participants who knew that HPV was a cancer-causing virus, most correctly
knew that HPV was contracted by unprotected sexual intercourse (81.1%) and that
there is a vaccine to protect against HPV (73.1%). However, 62.0% knew that the
vaccine was available in South Africa and only 31.0% knew the vaccine was free of
charge. CONCLUSION: The study revealed that students had limited knowledge of
cervical cancer, HPVand vaccine availability.
PMID- 29943595
TI - An illustrated booklet for reinforcing community health worker knowledge of
tuberculosis and facilitating patient counselling.
AB - BACKGROUND: Community health workers (CHWs) have facilitated the move to
decentralise tuberculosis (TB) management, but lack access to information
appropriate both for personal use and in patient interaction and education. AIM:
To explore the impact of a pictorial-based TB booklet on reinforcing CHW
knowledge and facilitating patient counselling. SETTING: This study was conducted
in local primary health care clinics and the Hospice in Grahamstown, Eastern Cape
Province in South Africa. METHODS: Quantitative and qualitative methods were
used. A simple, 17-page, A5 booklet containing pictograms and simple text was
designed in collaboration with CHWs who advised on preferred content. Its
influence on knowledge was assessed in 31 CHWs using a 17-item questionnaire in a
before-and-after study. The experiences of CHWs using the booklet were
qualitatively explored using focus group discussions (FGD) and semi-structured
interviews. RESULTS: Overall knowledge increased significantly from 70.6% to
85.3% (p < 0.001) with 8 of 17 questions significantly better answered at follow
up. These addressed meaning of side effects and side effect advice for patients,
cause and prevention of TB, action if a dose is forgotten, timing of dose in
relation to food intake and the possibility that not all patients are
cured.Community health workers reported using the booklet during patient
interactions, commenting that it enhanced their confidence in their own TB
related knowledge, improved recall of information and reduced uncertainty. They
appreciated the simplicity of the text and its userfriendliness because of the
inclusion of pictograms. The booklet was perceived to be valuable as a tool for
both patient education as well as improved communication with patients.
CONCLUSION: A simple, user-friendly TB booklet containing pictograms improved
CHWknowledge and acted as a valuable tool in patient communication and education.
PMID- 29943596
TI - Burnout among rural hospital doctors in the Western Cape: Comparison with
previous South African studies.
AB - BACKGROUND: Burnout among doctors negatively affects health systems and,
ultimately,patient care. AIM: To determine the prevalence of burnout among
doctors working in the district health system in the Overberg and Cape Winelands
districts of the Western Cape Province and to compare the findings with those of
previous South African studies. SETTING: Rural district hospitals. METHODS:
During 2013, a validated questionnaire (Maslach Burnout Inventory) was sent to 42
doctors working in the district health system within the referral area of the
Worcester Hospital, consisting of the Overberg health district and the eastern
half of the Cape Winelands. RESULTS: Response rate was 85.7%. Clinically
significant burnout was found among 81% of respondents. High levels of burnout on
all three subscales were present in 31% of participants.Burnout rates were
similar to those of a previous study conducted among doctors working in the Cape
Town Metropolitan Municipality primary health care facilities. Scores for
emotional exhaustion (EE) and depersonalisation (DP) were greater than those of a
national survey;however, the score for personal accomplishment (PA) was greater.
EE and PA scores weresimilar to that of a study of junior doctors working in the
Red Cross Children's Hospital;however, EE was smaller. CONCLUSION: This study
demonstrates high burnout rates among doctors working at district level
hospitals, similar to the prevalence thereof in the Cape Town Metropolitan
primary health care facilities. Health services planning should include
strategies to address and prevent burnout of which adequate staffing and improved
work environment are of prime importance.
PMID- 29943597
TI - The prevalence of underweight in children aged 5 years and younger attending
primary health care clinics in the Mangaung area, Free State.
AB - BACKGROUND: The Constitution of South Africa stipulates that all children have
the right to basic nutrition; however, a great number of South African children
are underweight for age. It is important to address malnutrition as it is
associated with more than 50% of all child deathsin developing countries and also
increases the risk for infective diseases. AIM: To determine the prevalence of
underweight in children aged 5 years and younger attending primary health care
clinics in the Mangaung area, Free State, and determine the possible underlying
causes thereof. SETTING: Six preselected primary health care clinics in the
Mangaung area. METHODS: This was a cross-sectional study. Demographic and
clinical information and anthropometric measurements were collected from the
children's Road-to-Health clinic cards,obtained from the children's caregivers.
RESULTS: In total, 240 children were included, of which 51.7% were girls. The
median age was 7.5 months. The weight-for-age graph revealed that 7.7% (95%
confidence interval: 4.8%;11.9%) of children were underweight or severely
underweight for age. Length-for-age and weight-for-height graphs were mostly
incomplete. Underweight children differed from normal weight children regarding
birth weight (low birth weight 70.6% vs. 12.4%) and history of malnutrition
(60.0% vs. 7.1%). CONCLUSION: The prevalence of underweight in children aged 0-5
years attending primary health care clinics in Mangaung is 7.7% based on
information available from Road-to-Healthcards. This figure could be higher if
these cards were filled in more accurately. A low birth weight and history of
malnutrition are associated with underweight.
PMID- 29943598
TI - Decolonising the mindsets, attitudes and practices of the allopathic and
indigenous health practitioners in postcolonial society: An exploratory approach
in the management of patients.
AB - BACKGROUND: The indigenous health care system continues in the postcolonial era
to be perceived by antagonists as a threat to Western medicine. It has been
associated with 'witchcraft', actively discouraged and repressed through official
government prohibition laws. Despite that, human immunodeficiency virus and
acquired immunodeficiency syndrome(HIV and AIDS) patients consult both allopathic
and indigenous health practitioners. AIM: The study explored a collaboration
model between allopathic and traditional health practitioners in the management
of patients living with HIV and AIDS in postcolonial South Africa. SETTING: We
conducted six combined focus group discussions and four separate group
discussions with each category of co-researchers. METHODS: Combined and separate
focus group discussions were conducted with community members, allopathic and
indigenous health practitioners, applying the cyclical method in the
decolonisation process. Their perceptions and experiences in the management of
HIV and AIDS patients were explored, and finally decolonisation strategies
suitable for collaboration in their context were identified. RESULTS: The two
health systems were rendering services to the same HIV and AIDS communities.Lack
of communication created confusion. Collaboration was long overdue. A change in
mindsets, attitudes and practices among practitioners was critical, with an
acknowledgementthat 'neither health system is better than the other, but the two
should be complementary, recognising that the culture and beliefs of patients
influence their health-seeking behaviour'. CONCLUSION: Co-researchers were
committed to working together in the fight against HIV and AIDS infections. Their
model for collaboration addresses the challenges of patients' secrecy, treatment
overdose and the abandonment of antiretroviral treatment. Through the application
of a decolonisation process, their mindsets, attitudes and practices towards each
other were changed, enabling the joint development of a custom model for
collaboration between allopathic health practitioners and indigenous health
practitioners in the management of patients living with HIV and AIDS.
PMID- 29943600
TI - Sexual assault survivors' perspectives on clinical follow-up in the Eden
District, South Africa: A qualitative study.
AB - BACKGROUND: Although effective follow-up of sexual assault survivors is linked to
optimal recovery, attendance at follow-up consultations is poor. It is therefore
essential that health care providers maximise the benefit of follow-up care for
every sexual assault survivor. AIM: This study explored the personal experiences
of sexual assault survivors to better understand the enablers of, and barriers
to, attendance at follow-up consultations. METHODS: This phenomenological
qualitative study was conducted at the three hospitals which manage most sexual
assault survivors within the Eden District. Using purposive sampling, 10
participants were selected. Consenting participants shared their
experiencesduring semi-structured interviews with the researcher. RESULTS:
Authoritative, client-held documentation was a powerful enabler to accessing
follow-up care. Individualised, patient-centred care further enhanced
participants' access to, and utilisation of, health care services. The failure of
health care providers to integrate follow-up care for sexual assault survivors
into established chronic care services was a missedopportunity in the continuum
of care. Negative perceptions, based on others' or personal prior experience of
police, judicial and health care systems, were further barriers to follow-up
care. CONCLUSION: This study highlights the need of survivors of sexual assault
for integrated,patient-centred care, encompassing principles of good
communication. Committed actions of all stakeholders are necessary to tackle
negative perceptions that create barriers to follow-upcare. A simple practical
strategy, the provision of a scheduled appointment on official stationery, is
easy to effect at facility level. As a powerful enabler to follow-up care, this
should be implemented as a priority intervention.
PMID- 29943599
TI - Exploring a communication curriculum through a focus on social accountability: A
case study at a South African medical school.
AB - BACKGROUND: Good communication is integral to social accountability, and training
is included in medical curricula internationally. In KwaZulu-Natal, training is
conducted in English, in spite of most public sector patients being mother tongue
isiZulu speakers. Communication challenges with patients are common, but good
communication and African language teaching are not emphasised in teaching. AIM:
This study explored communication training and how it related to social
accountability at a single institution in KwaZulu-Natal. SETTING: This
exploratory, qualitative case study design at the medical school explored
participants' perceptions about communication and social accountability and
reviewed relevant educational documentation for evidence. METHODS: Purposive
sampling was used to select medical students, educators and stakeholders from the
educational and service platforms. Focus group discussions and semi-structured
interviews were conducted. The data were thematically analysed with reference to
Boelen's social obligation scale for medical schools. RESULTS: Good communication
was valued, but often poorly role-modelled. Participants agreed that
communication and isiZulu teaching were insufficiently supported to respond
adequately to the needs of local communities. Social accountability was not well
understood by students, while medical school educators and other stakeholders
indicated that, despite aspirations, this goal had not yet been achieved.
CONCLUSIONS: Learning isiZulu language and culture in an integrated manner in
both preclinical and clinical phases would improve communication with patients,
contribute to socially responsive health care, and better address health care
needs. Incorporating a social accountability framework in curriculum review would
highlight the importance of measuring health outcomes and community impacts, and
so enhance the educational mission of the medical school.
PMID- 29943601
TI - Tuberculosis infection control practices in a high-burden metro in South Africa:
A perpetual bane for efficient primary health care service delivery.
AB - BACKGROUND: Tuberculosis (TB) prevention, including infection control, is a key
element in the strategy to end the global TB epidemic. While effective infection
control requires all health system components to function well, this is an area
that has not received sufficient attention inSouth Africa despite the
availability of policy and guidelines. AIM: To describe the state of
implementation of TB infection control measures in a high-burden metro in South
Africa. SETTING: The research was undertaken in a high TB- and HIV-burdened
metropolitan area of South Africa. More specifically, the study sites were
primary health care facilities (PHC), thatamong other services also diagnosed TB.
METHODS: A cross-sectional survey, focusing on the World Health Organization
levels of infection control, which included structured interviews with nurses
providing TB diagnosis and treatment services as well as observations, at all 41
PHC facilities in a high TB-burdened and HIV-burdened metro of South Africa.
RESULTS: Tuberculosis infection control was poorly implemented, with few
facilities scoring 80% and above on compliance with infection control measures.
Facility controls: 26 facilities (63.4%) had an infection control committee and
12 (29.3%) had a written infection control plan. Administrative controls: 26
facilities (63.4%) reported separating coughing and noncoughing patients, while
observations revealed that only 11 facilities (26.8%) had separate waiting areas
for (presumptive) TB patients. Environmental controls: most facilities used open
windows for ventilation (n = 30; 73.2%); however, on the day of the visit, only
12 facilities (30.3%) had open windows in consulting rooms. Personal protective
equipment: 9 facilities (22%) did not have any disposable respirators in stock
and only 9 respondents (22%) had undergone fit testing. The most frequently
reported barrier to implementing good TBinfection control practices was lack of
equipment (n = 22; 40%) such as masks and disposable respirators, as well as the
structure or layout of the PHC facilities. The main recommendation to improve TB
infection control was education for patients and health care workers (n = 18;
33.3%). CONCLUSION: All levels of the health care system should be engaged to
address TB prevention and infection control in PHC facilities. Improved infection
control will address the nosocomial spread of TB in health facilities and keep
health care workers and patients safe from infection.
PMID- 29943602
TI - Training of workplace-based clinical trainers in family medicine, South Africa:
Before-and-after evaluation.
AB - BACKGROUND: The training of family physicians is a relatively new phenomenon in
the district health services of South Africa. There are concerns about the
quality of clinical training and the low pass rate in the national examination.
AIM: To assess the effect of a five-day course to train clinical trainers in
family medicine on the participants' subsequent capability in the workplace.
SETTING: Family physician clinical trainers from training programmes mainly in
South Africa, but also from Ghana, Uganda, Kenya, Malawi and Botswana. METHODS: A
before-and-after study using self-reported change at 6 weeks (N = 18) and a 360
degree evaluation of clinical trainers by trainees after 3 months (N = 33).
Quantitative data were analysed using the Statistical Package for Social
Sciences, and qualitative data wereanalysed thematically. RESULTS: Significant
change (p < 0.05) was found at 6 weeks in terms of ensuring safe and effective
patient care through training, establishing and maintaining an environment for
learning, teaching and facilitating learning, enhancing learning through
assessment, and supporting and monitoring educational progress. Family physicians
reported that they were better at giving feedback, more aware of different
learning styles, more facilitative and less authoritarian in their educational
approach, more reflective and critical of their educational capabilities and more
aware of principles in assessment. Despite this, the trainees did notreport any
noticeable change in the trainers' capability after 3 months. CONCLUSION: The
results support a short-term improvement in the capability of clinical trainers
following the course. This change needs to be supported by ongoing formative
assessment and supportive visits, which are reported on elsewhere.
PMID- 29943603
TI - Scaling community-based services in Gauteng, South Africa: A comparison of three
workforce-planning scenarios.
AB - BACKGROUND: The introduction of community-based services through community health
workers is an opportunity to redefine the approach and practice of primary health
care. Based on bestpractice community oriented primary care (COPC), a COPC
planning toolkit has been developed to model the creation of a community-based
tier in an integrated district health system. AIM: The article describes the
methodologies and assumptions used to determine workforce numbers and service
costs for three scenarios and applies them to the poorest 60% of the population
in Gauteng, South Africa. SETTING: The study derives from a Gauteng Department of
Health, Family Medicine (University of Pretoria) partnership to support
information and communication technology (ICT)-enabled COPC through community
based health teams (termed as ward-based outreach teams). METHODS: The modelling
uses national census age, gender and income data at small area level, provincial
facility and national burden of disease data. Service calculations take into
account multidimensional poverty, demand-adjusted burden of disease and available
work time adjusted for conditions of employment and geography. RESULTS: Assuming
the use of ICT for each, a health workforce of 14 819, 17 925 and 7303 is
required per scenario (current practice, national norms and full-time employed
COPC), respectively. Total service costs for the respective scenarios range from
R1.1 billion, through R947 million to R783 million. CONCLUSION: Modelling shows
that delivering ICT-enabled COPC with full-time employees is the optimal
scenario. It requires the smallest workforce, is the most economical, even when
individual community health worker costs of employment are twice those of current
practice, and is systemically the most effective.
PMID- 29943604
TI - Perceptions of young men at the Free State School of Nursing with regards to
teenage pregnancy.
AB - BACKGROUND: Teenage pregnancy is a socio-economic challenge and a serious public
health problem for communities in South Africa. It is, therefore, imperative that
effective interventions and programmes be implemented to address this problem. A
number of research studies have been conducted on teenage pregnancy in South
Africa, but their focus was mainly on teenage girls excluding young men's
involvement in teenage pregnancy. AIM: The aim of the study was to determine the
perceptions of young men between the ages of 18 and 23 years towards teenage
pregnancy. METHODS: A qualitative, explorative semi-structured interview
descriptive design was used toconduct the study. The study was guided by the
Johnson's Behavioral System Model. Purposive sampling was used to select 10
participants with whom semi-structured interviews were conducted. Thematic
analysis of data were performed. SETTING: The study was conducted in Free State
School of Nursing's two main campuses. RESULTS: The findings of this study
revealed that young men were not involved in reproductive health programmes
aiming to prevent teenage pregnancies. Father and son's poor communication on
issues related to sex and teenage pregnancy contributes to unprotected sexual
intercourse resulting in teenage pregnancy. Cultural and traditional practices
such as the withdrawal method, not using contraceptives, and misleading teachings
at the initiation schools contribute to risk factors of teenage pregnancy.
CONCLUSION: There is still a gap in reproductive health that needs to be filled
by involving young men to reduce teenage pregnancies. Involving young men in
reproductive health programmes could lead to a decreased number of teenage
pregnancies. Factors, such as cultural and traditional practices, and father and
son sexual health education, need to be taken into consideration to prevent
teenage pregnancies.
PMID- 29943605
TI - Clinical mentoring to improve quality of care provided at three NIM-ART
facilities: A mixed methods study.
AB - BACKGROUND: The South African Department of Health implemented the nurse
initiated management of antiretroviral treatment (NIM-ART) programme as a policy
to decentralise services. Increasing access to ART through nurse initiation
results in significant consequences. AIM: This study evaluated the quality of
care provided, the barriers to the effective rollout of antiretroviral services
and the role of a clinical mentor. SETTING: The study was conducted at three NIM
ART facilities in South Africa. One clinic provided a high standard of care, one
had a high defaulter rate, and at the third clinic, treatment failures were
missed, and routine bloods were not collected. METHODS: A mixed methods study
design was used. Data were collected using patient satisfaction surveys, review
of clinical records, facility audits, focus group interviews, field notes and a
reflection diary. RESULTS: NIM-ART nurses prescribed rationally and followed
antiretroviral guidelines.Mortality rates and loss to follow-up rates were lower
than those at the surrounding hospitals, and 91.1% of nurse-monitored patients
had an undetectable viral load after a year. The quality of care provided was
comparable to doctor-monitored care. The facility audits found recurrent
shortages of essential drugs. Patients indicated a high level of satisfaction.
Salary challenges,excessive workload, a lack of trained nurses and
infrastructural barriers were identified as barriers. On-going mentoring and
support by a clinical mentor strengthened each of the facilities, facilitated
quality improvement and stimulated health workers to address constraints.
CONCLUSION: Clinical mentors are the key to addressing institutional treatment
barriers and ensuring quality of patient care.
PMID- 29943606
TI - The role of community volunteers in PMTCT programme: Lessons from selected sites
in Zambia to strengthen health education on infant feeding and follow-up of HIV
positive mother-infant pair.
AB - BACKGROUND: A global debate surrounding health care delivery at the lowest level
of the community has aroused interest among researchers. In settings where
skilled health workforce is scarce, the community relies on volunteers to provide
care. AIM: To explore the role of community-based volunteers (CBVs) and their
perspectives on human immunodeficiency virus (HIV) and infant feeding to gain
insights into the implementation of prevention of mother-to-child transmission
(PMTCT) interventions at community level. SETTING: The study was conducted in
Lusaka using Ngombe and Chelstone health facilities to recruit participants.
Fieldwork took place from January 2014 to September 2014. METHODS: An exploratory
descriptive qualitative study employing focus group discussions was conducted
with CBVs. Convenient sampling was used to recruit 10 participants from each
site. All transcribed interviews were imported into the Nvivo 10 for open coding
and analysis. RESULTS: Although the role of community volunteers was to support
and teach mothers on infant feeding in relation to HIV, the known cultural norms
and practices had a bearing on how they tailored their information on
breastfeeding to mothers. However, their link of the community to the health
facilities cannot be overemphasised in these settings. CONCLUSION: The role of
community volunteers in PMTCT interventions can be strengthened by improving
their training through use of appropriate educational materials and support of
required resources. Lessons from these sites can inform future research to design
communitybased interventions and develop health education materials that are
sensitive to cultural norms and practices in this and similar settings.
PMID- 29943607
TI - Examining the impact of a Mindfulness-Based Stress Reduction intervention on the
health of urban South Africans.
AB - BACKGROUND: Mindfulness-based stress reduction (MBSR) has been found to have
significant health benefits in studies conducted in the global North. AIM: This
study examined the effects of MBSR on stress, mood states and medical symptoms
among urban South Africans to inform future research and clinical directions of
MBSR in local settings. SETTING: Participants completed an 8-week MBSR programme
based in central Cape Town. METHOD: A retrospective analysis of 276 clinical
records was conducted. Mindfulness, stress, negative and positive mood, medical
symptoms and psychological symptoms were assessed before and after the
intervention using self-report questionnaires. We compared pre and
postintervention scores and examined the relationship between changes in
mindfulness and changes in stress, mood and medical symptoms. RESULTS:
Mindfulness scores were significantly higher after intervention, both on the
Kentucky Inventory of Mindfulness Skills (KIMS) and the Mindful Attention
Awareness Scale (MAAS). Changes on the KIMS were associated with reductions in
stress, negative mood, psychological symptoms and total medical symptoms, and
improvement in positive mood. Changes in mindfulness, as measured by the MAAS,
were significantly correlated only with reduced total number of medical symptoms.
CONCLUSION: This study provides preliminary evidence for the positive health
impact of MBSR on urban South Africans, and in turn acceptability and feasibility
evidence for MBSR in South Africa and supports the case for larger trials in
different local settings.
PMID- 29943608
TI - Patient satisfaction and treatment adherence of stable human immunodeficiency
virus-positive patients in antiretroviral adherence clubs and clinics.
AB - BACKGROUND: South Africa has experienced a substantial increase in access to
antiretroviral treatment (ART) in recent years. Effective strategies to manage
access to treatment need to be incorporated into and implemented in ART
programmes. Antiretroviral treatment adherence clubs are a new strategy that is
being implemented in various parts of South Africa. AIM: The aim of the study was
to investigate treatment adherence and patient satisfaction of stable human
immunodeficiency virus (HIV) patients on ART in ART adherence clubs and clinics.
SETTING: The study was conducted in the Eden district of the Western Cape, South
Africa. METHODS: A cross-sectional analytical study was conducted to examine the
relationships between patient satisfaction and treatment adherence in ART
adherence clubs and clinics in the Eden district, Western Cape province, South
Africa. Validated questionnaires were used to measure patient satisfaction and
self-reported treatment adherence. RESULTS: The study included 320 participants
(98 club and 222 clinic) from 13 primary health care clinics. The analyses showed
that higher levels of satisfaction could be predicted with club participants
compared to clinic participants (p = 0.05). There was no significant difference
between clinic and club participants with regards to treatment adherence.
However, being adherent was more likely in participants who were satisfied (odds
ratio = 3.18, 95% confidence interval [1.14-7.11], p < 0.01). CONCLUSION:
Antiretroviral treatment adherence clubs provide a service that patients are more
satisfied with although they are not more adherent to treatment. This strategy
may be effective for the delivery of long-term care for patients on ART.
PMID- 29943609
TI - Bereavement overload and its effects on, and related coping mechanisms of health
care providers and ward administrators at National District Hospital in
Bloemfontein, Free State.
AB - BACKGROUND: Patient death is an event that all health care workers will face at
some point. Beyond the family, the greatest emotional strain is on people who
work directly with the patient and family. Bereavement overload occurs after
multiple losses without time for normal grief in between. AIM: To investigate
bereavement overload, its effects and related coping mechanisms of personnel
working in adult medical wards. SETTING: Four adult medical wards at National
District Hospital, Bloemfontein. METHODS: An analytical cross-sectional study
design was performed with the aid of an intervieweradministered questionnaire.
The target population included health care providers (13 doctors and 20 nurses),
eight final-year medical students, and four administrative staff working in
thefour adult medical wards at National District Hospital, during August to
October 2016. RESULTS: Half (48.9%) of the 45 participants reported bereavement
overload. None of the medical students reported bereavement overload compared to
60.0% of nurses, 75.0% of administrative staff and 53.9% of doctors. Nearly two
thirds (64.5%, n = 29) stated that they suffered from compassion fatigue. The
majority of participants (62.2%) used only positive coping mechanisms. The use of
negative coping mechanisms correlated directly with a longer duration in the
medical field. CONCLUSION: With a 49% prevalence of bereavement overload, it is
important that support systems are in place to prevent the effects of negative
coping mechanisms. The desirable outcome is that health care providers, who
suffer from bereavement overload, experience compassion satisfaction and become
more dedicated to the patients' well-being without expense to themselves.
PMID- 29943610
TI - Chronic substance use and self-harm in a primary health care setting.
AB - BACKGROUND: Chronic substance use (CSU) is associated with health problems,
including selfharm, placing a significant burden on health care resources and
emergency departments (EDs). This is problematic in low- and middle-income
countries like South Africa (SA), where primary care facilitates and emergency
departments (EDs) are often poorly resourced. AIM: To investigate the
epidemiology of CSU and self-harm and to consider the implications for primary
health care service delivery and suicide prevention in SA. METHODS: Data were
collected from 238 consecutive self-harm patients treated at the emergency
department (ED) of an urban hospital in SA. The data were analysed using
bivariate and multivariate analyses. RESULTS: Approximately 37% of self-harm
patients reported CSU. The patients in the CSU subgroup, compared to other self
harm patients, were more likely to be men (odds ratio[OR] = 8.33, 95% confidence
interval [CI] = 3.19-20.9, p < 0.001), to have self-harmed by inflicting damage
to their body tissue OR = 4.45, 95% CI = 1.77-11.2, p < 0.01) and to have a
history of self-harm (OR = 3.71, 95% CI = 1.44-9.54, p = 0.007). A significantly
smaller proportion of CSU patients, compared to other self-harm patients, were
referred for psychiatric assessment (OR = 8.05, 95% CI = 4.16-15.7, p < 0.001).
CONCLUSION: The findings of this study confirm that CSU is associated with
greater service utilisation and repetition of self-harm among patients in primary
health care settings. Treating self-harm as the presenting problem within primary
care settings does not necessarily ensure that patients receive the care that
they need. It might be helpful to include psychiatric assessments and screening
for CSU as an integral component of care for self-harm patientswho present in
primary health care settings.
PMID- 29943611
TI - Scoping review of risk factors of and interventions for adolescent repeat
pregnancies: A public health perspective.
AB - BACKGROUND: Adolescent repeat pregnancy is of importance in public health because
the birth of a second child to an adolescent mother compounds the adverse
medical, educational, socioeconomic and parenting outcomes. Repeat pregnancy in
adolescence is not only an international phenomenon but also a local concern as
it also occurs in South Africa. The prevalence of adolescent repeat pregnancy in
Durban, KwaZulu-Natal, was reported as 17.6% in 2013. AIM: This review aimed to
gather relevant information from national and international sources to inform
practice and to provide an understanding of what is known about the risk factors
of and the interventions for adolescent repeat pregnancy. METHODS: A scoping
review was undertaken using the Arksey and O'Malley framework. An electronic
search was conducted using PubMed, Medline, Science Direct, Ebscohost, Sage and
Wiley Online and Google Scholar. RESULTS: The search identified 3032 citations.
After a review of the full text articles, 26 articles met the inclusion criteria.
Risk factors pertaining to adolescent repeat pregnancy are categorised according
to individual factors, partner relationship factors, family factors, peer
factors, and social and community factors. Interventions to reduce adolescent
repeat pregnancy have been largely influenced by the ecological framework. Across
studies, adolescent mothers who received medical, psychosocial, educational, and
family planning support experienced lower rates of repeat pregnancy. CONCLUSION:
A single 'one-size-fits-all' intervention for adolescent repeat pregnancy
prevention is unlikely as different strategies were employed by the intervention
programmes in this scoping review.
PMID- 29943612
TI - The development of the visual screening tool for anxiety disorders and
depression: Addressing barriers to screening for depression and anxiety disorders
in hypertension and/or diabetes.
AB - BACKGROUND: There is a lack of screening tools for common mental disorders that
can be applied across cultures, languages and levels of education in people with
diabetes and hypertension. Aim: To develop a visual screening tool for depression
and anxiety disorders that is applicable across cultures and levels of education.
Setting: Participants were purposively recruited from two not-for-profit
organisations and two public health facilities - a maternal mental health unit
and a primary health care centre. Method: This was a qualitative cross-sectional
study. Thirteen drawings based on the Hospital Anxiety and Depression Scale
depicting symptoms of anxiety disorders and depression were drawn. Participants
described emotions and thoughts depicted in the drawings. Data were analysed
through content analysis. Results: Thirty-one women (66%) and 16 men (34%)
participated in the development of the visual screening tool. The mean age was 34
(standard deviation [SD] 12.46). There were 32 (68%) black participants, 11 (23%)
mixed race participants and 4 (9%) white participants. Two participants (4%) had
no schooling, 14 (31%) primary schooling, 8 (18%) senior schooling, 13 (29%)
matric qualification and 8 (18%) had post-matric qualification. Participants
correctly described 10 out of the 13 visual depiction of symptoms as associated
with depression and anxiety disorders, with no differences between levels of
education and cultural groups. Conclusion: Ten drawings were appropriate for
inclusion in the visual screening tool for anxiety disorders and depression
(VISTAD). The VISTAD will be validated against the mini international
neuropsychiatric interview (MINI) in a primary care population with hypertension
and/or diabetes.
PMID- 29943614
TI - Why high tech needs high touch: Supporting continuity of community primary health
care.
AB - BACKGROUND: Integrated care through community-oriented primary care (COPC)
deployed through municipal teams of community health workers (CHWs) has been part
of health reform in South Africa since 2011. The role of COPC and integration of
information and communication technology (ICT) information to improve patient
health and access to care, require a better understanding of patient social
behaviour. Aim: The study sought to understand how COPC with CHWs visiting
households offering health education can support antenatal follow-up and what the
barriers for access to care would be. Method: A mixed methodological approach was
followed. Quantitative patient data were recorded on an electronic health record
keeping system. Qualitative data collection was performed through interviews of
the COPC teams at seven health posts in Mamelodi and telephonic patient
interviews. Interviews were analysed according to themes and summarised as
barriers to access care from a social and community perspective. Results: An
integrated COPC approach increased the number of traceable pregnant women
followed up at home from 2016 - 2017. Wrong addresses or personal identification
were given at the clinic because of fear of being denied care. Allocating
patients correctly to a ward-based outreach team (WBOT) proved to be a challenge
as many patients did not know their street address. Conclusion: Patient health
data available to a health worker on a smartphone as part of COPC improve patient
traceability and follow-up at home making timely referral possible. Health system
developments that support patient care on community level could strengthen
patient health access and overall health.
PMID- 29943613
TI - Investigating the interaction between human immunodeficiency virus, nutrition,
and disability: A cross-sectional observational study.
AB - BACKGROUND: The average lifespan of people with human immunodeficiency virus
(HIV) has increased because of the enhanced access to anti-retroviral treatment.
This increased longevity has led to a heightened focus on the comorbidities which
may arise, allowing a clearer understanding of the contextual, personal,
psychological and functional problems and their interrelations. Disability
(functional limitations) and insufficient nutritional intake may interact
cyclically with HIV and/or acquired immunodeficiency syndrome (AIDS); however, no
research to date has investigated this interaction. Aims: The objective of this
article was to report on the nutritional outcomes using albumin and body mass
index outcomes as a subset of a larger study among adults living with HIV and/or
AIDS. Setting: This study was conducted at a large HIV clinic based in an urban
area in Johannesburg, South Africa, which provides HIV treatment and support to
over 6000 persons with HIV and TB. This clinic is part of a large public health
regional hospital where extensive HIV research is undertaken. Methods: This study
was a cross-sectional observational study. The sample composed of 278
participants between 18 and 65 years of age and had been on highly active
antiretroviral therapy (HAART) for more than six months. Statistical analyses
were performed using the Statistical Package for the Social Sciences. Results:
The results indicated that albumin level had significant inverse associations
with functional limitations and physical health symptoms. Women were
significantly more likely to have lower nutritional levels. A logistic regression
analysis suggested that gender and physical health symptoms were the primary
predictors of albumin levels. Conclusion: The findings presented in this article
can be applied to HIV and/or AIDS treatment programmes, such as HAART. It re
emphasises the importance of providing individuals on anti-retroviral therapy
with affordable and adequate nutrition, education on the importance of
nutritional intake and the benefits of potentially adopting supplement
programmes. As females seem to be more adversely affected by low nutritional
levels, with the findings showing an increased likelihood of developing physical
health symptoms, focus also needs to be given to cultural or social factors that
impact nutritional intake in women.
PMID- 29943615
TI - Predictors of post-partum family planning uptake in Webuye Hospital, western
Kenya.
AB - BACKGROUND: A short inter-pregnancy interval increases the risk for maternal and
neonatal deaths in addition to other pregnancy complications including: preterm
delivery, low birth weight, anaemia and premature rupture of membranes. However,
only one half of Kenyan women, who have no desire to conceive immediately after
birth, are using contraception one year after delivery. Aim: The aim of this
study was to determine the predictors of uptake of post-partum family planning
(PPFP). Setting: The study was conducted among post-partum women accompanying
their children for their first measles vaccination at Webuye County Hospital
(WCH), in western Kenya. Methods: This was a cross-sectional study involving 259
randomly sampled post-partum women, accompanying their children for their first
measles vaccination. A structured, interviewer-administered questionnaire was
used to collect data. Logistic regression was used to identify correlates of PPFP
uptake. Results: The uptake of PPFP among women at 9 months post-partum at WCH
was found to be 78.4% +/- 5.0%. The odds of PPFP uptake among women living with
their sexual partners was 88.2% less than among those not living with their
partners with the true population effect between 97% and 51% (OR = 0.118; 95% CI:
0.028-0.494; p = 0.003). Conclusions: Not living with her sexual partner in the
same house is the key predictor of a woman's PPFP uptake in WCH. This study
recommends that any programme aimed at improving post-partum contraceptive use in
WCH should target women who live with their partners in the same house.
PMID- 29943616
TI - Intimate partner violence: The need for an alternative primary preventive
approach in Botswana.
AB - Intimate partner violence is a common social problem which causes considerable
relationship stress and results in significant morbidity and mortality of the
victims. Botswana, like many other countries in sub-Saharan Africa, has tried to
address the problem of intimate partner violence with legislations prescribing
punitive measures for the perpetrators and protection for the victims. The
effectiveness of these measures in reducing the prevalence of intimate partner
violence is doubtful. This article is to motivate for an alternative primary
preventive approach to the problem as a more pragmatic option.
PMID- 29943617
TI - Could an increase in vigilance for spinal tuberculosis at primary health care
level, enable earlier diagnosis at district level in a tuberculosis endemic
country?
AB - BACKGROUND: Expert clinicians and researchers in the field of spinal tuberculosis
(STB) advocate for early identification and diagnosis as a key to reducing
disability, severity of disease, expensive surgery and death, especially in
tuberculosis (TB) endemic countries like South Africa. South Africa has the
highest incidence per capita of tuberculosis in the world, and a conservative
estimate of the incidence of STB in South Africa is 8-16:100 000. People living
with STB may initially present to primary health care (PHC) centres, where the
opportunity exists for early identification. Spinal pain is the most common
presentation of STB, but even this symptom may not be present. Occasionally the
only symptoms are neurological injury, dysphagia or referred pain. Computerised
tomography-guided biopsy remains the diagnostic gold standard for STB. AIM: A
narrative review was undertaken to investigate the evidence available that could
assist with the early diagnosis of STB. METHOD: Articles were searched for and
retrieved from three databases and assessed for quality and relevance to primary
settings in a TB endemic country. RESULTS: The following evidence-based,
affordable and available tools could facilitate early diagnosis of STB at PHC and
district hospital levels: (1) back pain screening questions, undressed spinal
physical examination, HIV and antiretroviral therapy history, (2) erythrocyte
sedimentation rate, C-reactive protein, platelets, haemoglobin, white cell count
(WCC), sputum for GeneXpert and accurate weight measurement, (3) physiotherapy
and/or medical and/or speech therapy assessment, (4) full spinal radiograph,
chest radiograph, abdominal ultrasound, urine lipoarabinomannan (LAM) if CD4 <
200 and ultrasound-guided biopsy of superficial abscesses, (5) clear referral
guidelines at all levels, (6) a positive response to treatment to confirm the
diagnosis. CONCLUSION: These affordable and simple actions at PHC and district
levels could facilitate earlier diagnosis of STB.
PMID- 29943618
TI - Legal duties, professional obligations or notional guidelines? Screening,
treatment and referral of domestic violence cases in primary health care settings
in South Africa.
AB - BACKGROUND: Since 2013, approximately 4400 women have been murdered by their
partners in South Africa. This is five times higher than the per capita global
average. Domestic violence is known to be cyclical, endemic and frequently
involves multiple victims. It also becomes progressively more dangerous over time
and may lead to fatalities. In 2012, the Health Professions Council of South
Africa released a domestic violence protocol for emergency service providers.
This protocol, or screening guidelines, includes assessing future risk to
domestic violence, providing physical and psychosocial care, documentation of
evidence of abuse and informing patients of their rights and the services
available to them. The extent to which these guidelines have been circulated and
implemented, particularly by general health care practitioners (HCPs), is
unknown. AIM: We review international treaties to which South Africa is a
signatory, as well as national legislation and policies that reinforce the right
to care for victims of domestic violence, to delineate the implication of these
laws and policies for HCPs. METHOD: We reviewed literature and analysed national
and international legislation and policies. RESULTS: The 'norms' contained in
existing guidelines and currently practiced in an ad hoc manner are not only
compatible with existing statutory duties of HCPs but are in fact a natural
extension of them. CONCLUSION: Proactive interventions such as the use of
guidelines for working with victims of domestic violence enable suspected cases
of domestic violence to be systematically identified, appropriately managed,
properly referred, and should be adopted by all South African HCPs.
PMID- 29943619
TI - Calgranulin C (S100A12) Is Differentially Expressed in Subtypes of Chronic
Rhinosinusitis.
AB - Background Calgranulin C (S100A12) is an innate immune peptide at the air-mucosal
interface associated with neutrophil involvement, which when overexpressed has
been implicated as a biomarker of inflammatory diseases. Decreased epithelial
expression of certain innate immune peptides has been reported in chronic
rhinosinusitis (CRS). We hypothesized that S100A12 is differentially expressed in
the sinonasal mucosa of patients with CRS compared to controls and that S100A12
is a potential biomarker of CRS-specific quality of life (QOL) and disease
severity. Methods A prospective observational study was conducted which included
70 patients: 17 controls, 28 having CRS without (CRSsNP), and 25 with (CRSwNP)
nasal polyps. The expression of S100A12 and human neutrophil elastase (HNE) was
assessed in the anterior ethmoid tissues from all patients using enzyme-linked
immunosorbent assay (ELISA) and immunohistochemical (IHC) analyses. Disease
specific QOL (Rhinosinusitis Disability Index) and disease severity (computed
tomography [CT] and endoscopy) were evaluated and correlated to the expression
levels of S100A12. Results S100A12 and HNE were significantly elevated in
patients with CRSsNP compared to normal controls ( P < .05 and P < .001,
respectively) and patients with CRSwNP ( P < .05 and P < .001, respectively), as
measured by ELISA and IHC analyses. Patients with CRS exhibited worse CRS
specific disease severity compared to normal controls ( P < .05), and the
increased protein levels of S100A12 were significantly correlated to disease
severity, represented by CT scores ( P < .05). Conclusions S100A12 is
differentially expressed in CRS subtypes and is significantly elevated in
patients with CRSsNP and associated with CRS-specific disease severity.
PMID- 29943620
TI - The Mathilde Krim Effect as a Way to Overcome the Matilda Effect.
AB - The Matilda effect illustrates how the contributions of women to science have
been historically attributed to their male colleagues in some circumstances. This
effect may perpetuate and even increase the gender gap we currently face.
Recognizing the work of great women who led our way and committed their careers
to transform society can offer the gender-positive role models required to speed
up the movement toward gender equity in science. As a way to overcome the Matilda
effect and begin to acknowledge the contributions of outstanding women
scientists, I propose to embrace the Mathilde Krim effect, and commemorate how
the will of a woman had such a profound impact on the fight against HIV and AIDS.
PMID- 29943621
TI - Medical Students' Perspectives on HIV Prevention Education in the Preclinical
Years.
PMID- 29943622
TI - Protection of Kidney Function with Human Antioxidation Protein alpha1
Microglobulin in a Mouse 177Lu-DOTATATE Radiation Therapy Model.
AB - AIMS: Peptide receptor radionuclide therapy (PRRT) is in clinical use today to
treat metastatic neuroendocrine tumors. Infused, radiolabeled, somatostatin
analog peptides target tumors that are killed by irradiation damage. The
peptides, however, are also retained in kidneys due to glomerular filtration, and
the administered doses must be limited to avoid kidney damage. The human radical
scavenger and antioxidant, alpha1-microglobulin (A1M), has previously been shown
to protect bystander tissue against irradiation damage and has pharmacokinetic
and biodistribution properties similar to somatostatin analogs. In this study, we
have investigated if A1M can be used as a renal protective agent in PRRT.
RESULTS: We describe nephroprotective effects of human recombinant A1M on the
short- and long-term renal damage observed following lutetium 177 (177Lu)
DOTATATE (150 MBq) exposure in BALB/c mice. After 1, 4, and 8 days (short term),
177Lu-DOTATATE injections resulted in increased formation of DNA double-strand
breaks in the renal cortex, upregulated expression of apoptosis and stress
response-related genes, and proteinuria (albumin in urine), all of which were
significantly suppressed by coadministration of A1M (7 mg/kg). After 6, 12, and
24 weeks (long term), 177Lu-DOTATATE injections resulted in increased animal
death, kidney lesions, glomerular loss, upregulation of stress genes,
proteinuria, and plasma markers of reduced kidney function, all of which were
suppressed by coadministration of A1M. Innovation and Conclusion: This study
demonstrates that A1M effectively inhibits radiation-induced renal damage. The
findings suggest that A1M may be used as a radioprotector during clinical PRRT,
potentially facilitating improved tumor control and enabling more patients to
receive treatment. Antioxid. Redox Signal. 00, 000-000.
PMID- 29943623
TI - High Seroprevalence of Syphilis Among HIV-Infected Patients and Associated
Predictors.
PMID- 29943624
TI - Are we SHARP enough? The importance of adequate patient selection in sorafenib
treatment for hepatocellular carcinoma.
AB - BACKGROUND: Upon FDA/EMEA registration for hepatocellular carcinoma (HCC),
sorafenib received a broader therapeutic indication than the eligibility criteria
of the landmark SHARP trial. This allowed treatment of SHARP non-eligible
patients in daily clinical practice. AIM: To assess sorafenib efficacy and safety
in SHARP eligible and non-eligible patients, and determine the validity of the
current therapeutic indication as described by the FDA/EMEA. PATIENTS AND
METHODS: Consecutive patients treated with sorafenib for advanced HCC at two
Dutch tertiary referral centers between 2007 and 2016 were analyzed
retrospectively. Primary outcome was overall survival (OS). Secondary outcomes
were time to progression (TTP), response rate, adverse events and reasons for
discontinuation. Outcomes were compared between SHARP eligible and non-eligible
patients. RESULTS: One hundred and ninety-three of 257 (75%) patients were SHARP
eligible. SHARP eligible patients (9.5 months, 95% CI 7.7-11.3) had a longer
median OS than non-eligible patients (5.4 months, 95% CI 3.6-7.1) (log-rank p <
.001). SHARP non-eligible patients were more often Child-Pugh B, had higher AST
and ALT levels and developed more grade 3-4 liver dysfunction (44 versus 23%, p <
.001) during treatment. SHARP ineligibility remained the strongest predictor of
OS (HR 1.78, 95% CI 1.32-2.41) and an independent predictor of TTP (HR 1.45, 95%
CI 1.05-2.00) in multivariable analysis. CONCLUSIONS: Landmark trial outcomes of
sorafenib for HCC are reproducible in daily practice, provided that the SHARP
eligibility criteria are respected. Based on the findings of this and previous
studies, sorafenib usage should be restricted to Child-Pugh A patients.
PMID- 29943625
TI - Recurrent episodes of feline lower urinary tract disease with different causes:
possible clinical implications.
AB - Case series summary While descriptions of cats with recurrent episodes of feline
idiopathic cystitis (FIC) exist, little is published on cats with recurrent
episodes of feline lower urinary tract disease (FLUTD) where the cat is diagnosed
with different causes of FLUTD at separate episodes. In the present paper, six
cats, originally part of larger studies of FLUTD among Norwegian cats, are
described. In the project period (2003-2009), these cats had several episodes of
FLUTD. At each episode, the cats had a complete physical examination, abdominal
imaging, blood work, urinalysis and urine culture performed. Two of the cats
initially presented with urolithiasis and subsequently with episodes of non
obstructed FIC. Four of the cats presented with non-obstructed FIC at one or more
episodes, but were later diagnosed with urolithiasis or bacterial cystitis
without prior catheterisation or other known predisposing factors. Relevance and
novel information Cats with recurrent episodes of FLUTD may present with
different causes at different times. The need to thoroughly work-up cats with
recurrent episodes of FLUTD at each presentation is emphasised. FIC may be
considered as a predisposing factor in cats developing urolithiasis or bacterial
cystitis; alternatively, interrelated FLUTD disease mechanisms exists. Thus,
applying multimodal environmental enrichment and modification (MEMO) to cats with
signs of FLUTD independent of diagnosis should be considered.
PMID- 29943626
TI - High Concentration of Insulin Induces MUC5AC Expression via Phosphoinositide 3
Kinase/AKT and Mitogen-activated Protein Kinase Signaling Pathways in Human
Airway Epithelial Cells.
AB - Background Insulin is involved in a glucose homeostatic regulation and a cellular
metabolism via phosphorylation of phosphoinositide 3 kinase (PI3K) pathway and
mitogen-activated protein kinase (MAPK) pathway. Hyperinsulinemia reduces insulin
sensitivity and is an obvious potential factor affecting airway inflammation in
chronic airway diseases. MUC5AC is a major secreted mucin, which plays a critical
role in inflammatory response in the respiratory tract. However, the relationship
between insulin and MUC5AC expression has not been studied. Objective This study
investigated the effect and the brief signaling pathway of high concentration of
insulin (HI) on MUC5AC expression in human airway epithelial cell. Methods In NCI
H292 cells and primary cultures of normal nasal epithelial cells, the effect and
signaling pathway of HI on MUC5AC expression were investigated using reverse
transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme
immunoassay, and immunoblot analysis with several specific inhibitors and small
interfering RNA (siRNA). Results HI significantly increased MUC5AC expression and
activated PI3K/AKT, extracellular signal-related kinase 1/2 (ERK1/2) and p38
MAPKs. The specific PI3K and AKT inhibitor as well as knockdown of AKT1 and AKT2
by the respective siRNAs significantly blocked HI-mediated expression of MUC5AC.
Meanwhile, the specific ERK1/2 MAPK and p38 MAPK inhibitor as well as knockdown
of ERK1, ERK2, and p38 MAPK by the respective siRNAs also attenuated HI-induced
expression of MUC5AC. Conclusion The results of this study suggest that HI
induces MUC5AC expression via PI3K/AKT and MAPK signaling pathways in human
airway epithelial cells.
PMID- 29943627
TI - Swiss students and young physicians want a flexible goal-oriented GP training
curriculum.
AB - BACKGROUND: A growing shortage of general practitioners (GPs), in Switzerland and
around the world, has forced countries to find new ways to attract young
physicians to the specialty. In 2017, Switzerland began to fund hundreds of new
study places for medical students. This wave of young physicians will soon finish
University and be ready for postgraduate training. We hypothesized that an
attractive postgraduate training program would encourage interested young
physicians to pursue a GP career. METHODS: This is a cross-sectional survey of
young physicians from the Swiss Young General Practitioners Association (JHaS),
members of Cursus Romand de medecine de famille (CRMF), and all current medical
students (5th or 6th years) (n = 554) in Switzerland, excluding students
indicating definitely not to become GPs. We asked all if they were likely to
become a GP (Likert: 1-10), and then asked them to score general features of a GP
training curriculum, and likely effects of the curriculum on their career choice
(Likert scale). They then rated our model curriculum (GO-GP) for attractiveness
and effect (Likert Scales, open questions). RESULTS: Most participants thought
they would become GPs (Likert: 8 of 10). Over 90% identified the same features as
an important part of a curriculum ("yes" or "likely yes"): Our respondents
thought the GO-GP curriculum was attractive (7.3 of 10). It was most attractive
to those highly motivated to become GPs. After reviewing the curriculum, most
respondents (58%) felt GO-GP would make them more likely to become a GP. Almost
80% of respondents thought an attractive postgraduate training program like GO-GP
could motivate more young physicians to become GPs. CONCLUSIONS: Overall, medical
students and young physicians found similar features attractive in the general
and GO-GP curriculum, regardless of region or gender, and thought an attractive
curriculum would attract more young doctors to the GP specialty. Key points An
attractive postgraduate training program in general practice can attract more
young physicians to become GPs. In this study cross-sectional survey including
medical students (n = 242) and young physicians (n = 312) we presented general
features for a curriculum and a model curriculum for general practice training,
for evaluation of attractiveness to our study population. General practice
training curriculum provides flexibility in choice of rotations, access to short
rotations in a wide variety of medical specialties, training in specialty
practices as well, mentoring and career guidance by GPs and guidance in choosing
courses/certificate programs necessary for general practice. These findings help
building attractive postgraduate training programs in general practice and fight
GP shortage.
PMID- 29943628
TI - Comparison of field surveillance methods for and assessment of factors
potentially associated with the presence of free-roaming cats in a mixed-urban
environment.
AB - OBJECTIVE To evaluate 2 methods of surveying free-roaming cats (Felis catus) and
identify factors potentially associated with the presence of such cats in a mixed
urban environment. ANIMALS Free-roaming cats on and near The Ohio State
University campus. PROCEDURES The university campus and surrounding areas were
divided into zones classified by land-use category; 100 zones were selected for
surveillance of free-roaming cats by the line-transect method (with visual
observation). Twenty-three of the 100 zones were selected for surveillance by the
trail-camera method (motion-triggered still photography). Food resources in the
study site were mapped, and the presence of other animal species was recorded
with trail cameras. Potential associations between the number of cat sightings
and variables of interest were assessed by statistical methods, RESULTS There
were 6 cat sightings in 5 zones and 92 cat sightings in 9 zones with the line
transect and trail-camera methods, respectively. Cats were most frequently
detected off campus and in urban land-use zones. The number of cat sightings with
trail cameras was significantly correlated with the density of food resources but
not wildlife sightings in the area and was significantly greater at night than
during the day. CONCLUSIONS AND CLINICAL RELEVANCE The number of sightings with
the trail-camera method was substantially higher than that obtained with the line
transect method; however, identification of individual cats was generally not
possible, and population size could not be estimated with these methods.
Communities considering population control for free-roaming cats should consider
the use of trail cameras to identify areas with high free-roaming cat activity
and observation at night to gather baseline data. Easily accessible food waste
may attract free-roaming cats.
PMID- 29943629
TI - Amount of skin shrinkage affecting tumor versus grossly normal marginal skin of
dogs for cutaneous mast cell tumors excised with curative intent.
AB - OBJECTIVE To assess differences in skin shrinkage between grossly visible tumor
and grossly normal marginal skin of dogs for cutaneous mast cell tumors (MCTs)
excised with curative intent and to determine an equation to estimate
postexcisional gross tumor margins from preexcisional measurements and vice
versa. SAMPLE 19 cytologically confirmed and surgically excised cutaneous MCTs
obtained from dogs. PROCEDURES Tumors were measured in craniocaudal and
dorsoventral directions before excision, immediately after excision, and after
fixation in formalin. Both grossly visible tumor and surrounding grossly normal
skin that comprised the surgical margin were measured at each time point.
Percentage of shrinkage was compared among time points and between the tumor and
surrounding grossly normal skin. Patient and histopathologic variables were
correlated to skin shrinkage. RESULTS Overall shrinkage was 17.70%. The amount of
shrinkage within the grossly visible tumor (4.45%) was less than that within the
surrounding grossly normal skin (24.42%). Most of the shrinkage occurred
immediately after excision. There was no effect of age, sex, completeness of
excision, or degree of edema. Accuracy of an equation to estimate postexcisional
margins from preexcisional measurements was only 18.4%. CONCLUSIONS AND CLINICAL
RELEVANCE Grossly evident MCTs of dogs shrunk less than did the grossly normal
surrounding skin. Although an equation to estimate postexcisional margins from
preexcisional measurements could be derived, it likely would need to contain
additional variables not included in the study reported here. Until such an
equation exists, care must be used when extrapolating surgical margins from
histologic margins and vice versa.
PMID- 29943630
TI - Evaluation of leak pressure and closure time for double-layer esophagotomy
closure with an interrupted or a continuous suture pattern.
AB - OBJECTIVE To compare the leak pressure and amount of time required to perform
closure for 2 double-layer esophagotomy closure techniques. SAMPLE 28
intrathoracic esophageal segments harvested from 38 porcine cadavers. PROCEDURES
Longitudinal 3-cm esophagotomy incisions made in porcine cadaveric esophagi were
closed with 2 double-layer closure techniques. Fifteen incisions were closed with
a simple interrupted pattern, and 13 incisions were closed with a simple
continuous pattern. Leak pressure, bursting wall tension, and closure time were
compared between suture patterns by use of a t test or Mann-Whitney rank sum
test. RESULTS Median leak pressures differed significantly between segments
closed with the simple interrupted pattern (16.0 mm Hg; range, 5.4 to 54.9 mm Hg)
and the simple continuous pattern (38.7 mm Hg; range, 11.3 to 81.9 mm Hg). Median
bursting wall tension differed significantly between the simple interrupted
pattern (0.63 * 105 dynes/cm; range, 0.16 * 105 dynes/cm to 2.89 * 105 dynes/cm)
and the simple continuous pattern (1.79 * 105 dynes/cm; range, 0.44 * 105
dynes/cm to 4.70 * 105 dynes/cm). Mean +/- SD closure time differed significantly
between the simple interrupted pattern (19.2 +/- 2.0 minutes) and the simple
continuous pattern (14.7 +/- 1.5 minutes). CONCLUSIONS AND CLINICAL RELEVANCE In
the study reported here, double-layer simple continuous closure resulted in a
higher median postoperative leak pressure and higher median postoperative
bursting wall tension and could be performed more rapidly than the double-layer
simple interrupted closure on these porcine cadaveric specimens.
PMID- 29943633
TI - Evaluation of a fluorescence resonance energy transfer quantitative polymerase
chain reaction assay for identification of gyrA mutations conferring enrofloxacin
resistance in canine urinary Escherichia coli isolates and canine urine
specimens.
AB - OBJECTIVE To evaluate a fluorescence resonance energy transfer quantitative PCR
(FRET-qPCR) assay for detection of gyrA mutations conferring fluoroquinolone
resistance in canine urinary Escherichia coli isolates and canine urine
specimens. SAMPLE 264 canine urinary E coli isolates and 283 clinical canine
urine specimens. PROCEDURES The E coli isolates were used to validate the FRET
qPCR assay. Urine specimens were evaluated by bacterial culture and
identification, isolate enrofloxacin susceptibility testing, and FRET-qPCR assay.
Sensitivity and specificity of the FRET-qPCR assay for detection of gyrA
mutations in urine specimens and in E coli isolated from urine specimens were
computed, with results of enrofloxacin susceptibility testing used as the
reference standard. RESULTS The validated FRET-qPCR assay discriminated between
enrofloxacin-resistant and enrofloxacin-susceptible E coli isolates with an area
under the receiver operating characteristic curve of 0.92. The assay accurately
identified 25 of 40 urine specimens as containing enrofloxacin-resistant isolates
(sensitivity, 62.5%) and 226 of 243 urine specimens as containing enrofloxacin
susceptible isolates (specificity, 93.0%). When the same assay was performed on E
coli isolates recovered from these specimens, sensitivity (77.8%) and specificity
(94.8%) increased. Moderate agreement was achieved between results of the FRET
qPCR assay and enrofloxacin susceptibility testing for E coli isolates recovered
from urine specimens. CONCLUSIONS AND CLINICAL RELEVANCE The FRET-qPCR assay was
able to rapidly distinguish between enrofloxacin-resistant and enrofloxacin
susceptible E coli in canine clinical urine specimens through detection of gyrA
mutations. Therefore, the assay may be useful in clinical settings to screen such
specimens for enrofloxacin-resistant E coli to avoid inappropriate use of
enrofloxacin and contributing to antimicrobial resistance.
PMID- 29943632
TI - Hemodynamic effects of MK-467 following intravenous administration to isoflurane
anesthetized cats concurrently receiving dexmedetomidine.
AB - OBJECTIVE To evaluate the efficacy of each of 3 incremental doses of MK-467 for
alleviation of dexmedetomidine-induced hemodynamic depression in isoflurane
anesthetized cats. ANIMALS 6 healthy adult domestic shorthair cats. PROCEDURES
Each cat was anesthetized with isoflurane and received a target-controlled
infusion of dexmedetomidine estimated to maintain the plasma dexmedetomidine
concentration at 10 ng/mL throughout the experiment. Heart rate (HR) and direct
arterial pressures were measured at baseline (isoflurane administration only),
during dexmedetomidine infusion, and before and after IV administration of each
of 3 serially increasing doses (15, 30, and 60 MUg/kg) of MK-467. Cardiac index
(CI) and systemic vascular resistance (SVR) were recorded at baseline, during
dexmedetomidine infusion, and at the mean arterial pressure nadir after
administration of the 30- and 60-MUg/kg doses of MK-467. RESULTS Compared with
baseline values, the dexmedetomidine infusion significantly decreased HR and
increased arterial pressures. Each dose of MK-467 caused a significant decrease
in arterial pressures and a significant, albeit clinically irrelevant, increase
in HR (<= 10%). Following administration of the 30- and 60-MUg/kg doses of MK
467, all cats developed clinical hypotension (mean arterial pressure, < 60 mm Hg)
even though CI and SVR returned to baseline values. CONCLUSIONS AND CLINICAL
RELEVANCE Results indicated administration of small doses of MK-467 to isoflurane
anesthetized cats receiving dexmedetomidine restored CI and SVR, but caused a
substantial decrease in arterial pressures and only a marginal increase in HR.
Therefore, caution should be used when MK-467 is administered to alleviate
dexmedetomidine-induced hemodynamic depression in isoflurane-anesthetized cats.
PMID- 29943634
TI - Effects of a nutrient-enriched water on water intake and indices of hydration in
healthy domestic cats fed a dry kibble diet.
AB - OBJECTIVE To evaluate the effects of drinking nutrient-enriched water (NW) on
water intake and indices of hydration in healthy domestic cats fed a dry kibble
diet ad libitum. ANIMALS 18 domestic shorthair cats. PROCEDURES Group-housed cats
were assigned to tap water (TW; n = 9) or NW (9) groups. All cats received TW at
baseline (days -7 to -1). No changes were made to the food-water regimen for the
TW group. The NW group received NW instead of TW from days 0 through 10, then
received TW and NW in separate bowls (days 11 through 56). Food intake was
measured through day 10; liquid consumed by drinking was measured throughout the
study. Blood and urine samples were collected at predetermined times for
analyses; 48-hour urine collection (days 28 through 30 or 31 through 33) was
performed to assess output volume and aid endogenous creatinine-based glomerular
filtration rate (GFR) determination. Data were analyzed with linear mixed-effects
models. RESULTS Baseline TW and calorie intake were similar between groups. The
NW treatment was significantly associated with increased liquid consumption
during the treatment phase. Mean urine output was significantly higher in the NW
group (15.2 mL/kg/d) than in the TW group (10.3 mL/kg/d). Mean GFR (1.75 vs 1.87
mL/min/kg, respectively) did not differ between groups. Effects of treatment and
time were each significant for urine specific gravity and osmolality and urine
creatinine, phosphate, and urea nitrogen concentrations, with lower values for
the NW group. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that
consumption of the NW can increase liquid intake and improve measures of
hydration in healthy cats. These effects may offer health benefits to some cats
in need of greater water consumption.
PMID- 29943635
TI - Determination of minimum alveolar concentration and cardiovascular effects of
desflurane in positive-pressure ventilated sheep.
AB - OBJECTIVE To determine the minimum alveolar concentration of desflurane (MACDES)
and effects on cardiovascular variables in positive-pressure ventilated sheep.
ANIMALS 13 adult female sheep. PROCEDURES Anesthesia was induced with desflurane.
After a 30-minute equilibration at an end-tidal concentration of desflurane
(etDES) of 10.5%, an electrical stimulus (5 Hz/ms and 50 mA) was applied for 1
minute or until gross purposeful movement occurred. The etDES was then changed by
0.5% (modified up-down method), depending on whether a positive motor response
had been elicited, and stimulation was repeated. The MACDES was the etDES midway
between a positive and negative response. After MACDES was determined, etDES was
increased to 1.3 and 1.6 MACDES. Animals were allowed to equilibrate for 15
minutes, and cardiovascular, blood gas, acid-base, and hematologic variables were
measured. Times to induction of anesthesia, extubation, attainment of sternal
position, and standing and duration of anesthesia were recorded. RESULTS Mean +/-
SD MACDES was 9.81 +/- 0.79%. Times to intubation, extubation, and standing were
4.81 +/- 2.21 minutes, 14.09 +/- 4.05 minutes, and 32.4 +/- 12.5 minutes,
respectively. Duration of anesthesia was 226 +/- 22 minutes. Heart rate increased
significantly at induction of anesthesia but otherwise remained at preanesthetic
rates. Arterial blood pressures progressively decreased with increasing etDES;
pressures increased slightly only in response to noxious stimulation. CONCLUSIONS
AND CLINICAL RELEVANCE The MACDES determined here compared favorably with that
determined for other sheep populations and indicated similar anesthetic potency
as in other species. Desflurane caused dose-dependent arterial hypotension, which
indicated the need for careful blood pressure monitoring.
PMID- 29943636
TI - Microbial integrity of preservative-free alfaxalone in a multiple-use system for
two storage conditions and three handling techniques.
AB - OBJECTIVE To evaluate the microbial integrity of preservative-free cyclodextrin
based alfaxalone in a multiple-use system. SAMPLE 22 vials of preservative-free
alfaxalone. PROCEDURES 2 storage conditions (room temperature, 22 degrees C;
refrigerated temperature, 4 degrees C) and 3 handling techniques (closed system
transfer device, nonclosed dispensing pin, and manufacturer-supplied vial
stopper) comprised 6 treatment groups (3 replicates/group). An aliquot (0.5 mL)
was withdrawn from each vial daily for 14 days. Samples were immediately
inoculated into tryptic soy broth and incubated at 36 degrees C for 24 hours;
samples were subcultured onto 5% Columbia sheep blood agar and incubated for 48
hours. Isolated colonies were evaluated for identification. RESULTS There was no
evidence of microbial contamination of vials stored for 7 days in refrigeration
and handled with a protected port (closed system transfer device or nonclosed
dispensing pin). CONCLUSIONS AND CLINICAL RELEVANCE The US FDA prohibits the use
of alfaxalone beyond 6 hours after the vial stopper is broached (punctured), as
mandated for a preservative-free injectable medication. Findings for the study
reported here supported the use of alfaxalone for 7 days when refrigerated and
handled with a single puncture of the stopper by use of a protected port (closed
system transfer device or nonclosed dispensing pin). This would appear to be a
practical alternative for an injectable anesthetic. It would minimize drug waste
and the subsequent environmental impact for disposal of unused drug and allow
standardization of storage and handling protocols for alfaxalone use in
veterinary practices across the United States.
PMID- 29943637
TI - Effects of grape seed extract, lutein, and fish oil on responses of canine lens
epithelial cells in vitro.
AB - OBJECTIVE To determine the effects of grape seed extract (GSE), lutein, and fish
oil containing omega-3 fatty acids on oxidative stress, migration, proliferation,
and viability of lens epithelial cells (LECs). SAMPLE Lens capsules or cultured
LECs obtained from canine cadavers. PROCEDURES An antioxidant reductive capacity
assay was used to determine reducing capability of each substance. The LECs were
cultured and incubated with various substances, including N-acetyl cysteine
(NAC), when appropriate, and dimethyl sulfoxide (DMSO) as positive and vehicle
control substances, respectively. A dichlorofluorescein assay was used to
evaluate reactive oxygen species (ROS) production, and a 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyltetrazolium bromide assay was used to determine cell viability.
Ex vivo posterior capsule opacification (PCO) was used to evaluate LEC migration
and proliferation. RESULTS Antioxidant reductive effects of GSE surpassed those
of NAC, lutein, and fish oil containing omega-3 fatty acids. The GSE reduced ROS
production in LECs, compared with the DMSO vehicle control, whereas lutein was
pro-oxidative. All test substances reduced cell viability. Ex vivo PCO was not
altered by GSE, was decreased by lutein, and was increased by fish oil containing
omega-3 fatty acids, compared with results for the DMSO vehicle control.
CONCLUSIONS AND CLINICAL RELEVANCE Only GSE had significant antioxidant
capabilities and reduced ROS production; however, no effect on ex vivo PCO was
detected. Fish oil containing omega-3 fatty acids increased ex vivo PCO. No
conclusions could be made regarding antioxidant effects of these substances on
LECs. These findings suggested that the substances will not decrease PCO.
PMID- 29943638
TI - Evaluation of self-injurious behavior, thermal sensitivity, food intake, fecal
output, and pica after injection of three buprenorphine formulations in rats
(Rattus norvegicus).
AB - OBJECTIVE To assess effects of buprenorphine hydrochloride (BH), sustained
release buprenorphine (SRB), and high-concentration buprenorphine (HCB)
formulations in healthy rats. ANIMALS 8 Sprague-Dawley rats. PROCEDURES In a
crossover-design study, rats received BH (0.05 mg/kg), SRB (1.2 mg/kg), HCB (0.30
mg/kg), or 5% dextrose solution (0.2 mL/kg), SC, once. Self-injurious behavior
and thermal sensitivity (hind limb withdrawal latencies) were assessed prior to
injection (time 0) and 1, 4, 8, 12, and 24 hours after injection. Food intake,
kaolin intake, and fecal output were measured over 12-hour light and dark periods
before and after each treatment. Values were compared among treatments and time
points. RESULTS Self-injurious behavior was detected with all buprenorphine
treatments; scores were greater at all time points during the 12 hours after HCB
and 24 hours after SRB administration than at time 0. Percentage change in hind
limb withdrawal latencies from time 0 was higher with BH and HCB 1 hour after
injection than at other time points. Postinjection light-period food intake was
higher (BH and HCB) and dark-period food intake was lower (BH, HCB, and SRB),
compared with preinjection values for the same treatments. For SRB, postinjection
light-period kaolin intake was greater than the preinjection value, and
postinjection light- and dark-period kaolin intake was greater than that for
other treatments. CONCLUSIONS AND CLINICAL RELEVANCE Hypoalgesic effects were
briefly observed after administration of BH or HCB in healthy rats; adverse
effects were detected in some rats with all buprenorphine formulations. Studies
comparing effects of BH, SRB, and HCB in rats undergoing surgery or other noxious
stimuli are indicated to determine clinical benefits in this species.
PMID- 29943639
TI - Evaluation of topical ophthalmic ganciclovir gel for the treatment of dogs with
experimentally induced ocular canine herpesvirus-1 infection.
AB - OBJECTIVE To determine the in vitro half maximal effective concentration (EC50)
of ganciclovir for canine herpesvirus-1 (CHV-1) and to evaluate the efficacy of
ganciclovir ophthalmic gel in dogs with experimentally induced ocular CHV-1
infection. ANIMALS 10 specific pathogen-free adult Beagles. PROCEDURES
Cytotoxicity and EC50 of ganciclovir for CHV-1 were determined during in vitro
experiments. During an in vivo experiment, dogs with experimentally induced
ocular CHV-1 infections received 1 drop of 0.15% ganciclovir (ganciclovir group;
n = 5) or artificial tear (control group; 5) ophthalmic gel in both eyes 5 times
daily for 7 days, then 3 times daily for 7 days. For each dog, ophthalmic and
confocal microscopic examinations were performed at predetermined times to
determine severity of ocular disease and inflammation. Conjunctival swab
specimens were collected at predetermined times for PCR assay analysis to
determine CHV-1 shedding. RESULTS No in vitro cytotoxic effects were observed for
ganciclovir concentrations <= 500MUM. The EC50 of ganciclovir for CHV-1 was
37.7MUM. No adverse effects associated with ganciclovir were observed during the
in vivo experiment. Mean ocular disease and inflammation scores for the
ganciclovir group were significantly lower than those for the control group. Mean
duration of CHV-1 shedding for the ganciclovir group (0.4 days) was significantly
shorter than that for the control group (6.2 days). CONCLUSIONS AND CLINICAL
RELEVANCE Topical administration of 0.15% ganciclovir ophthalmic gel was well
tolerated and effective in decreasing clinical disease scores, ocular tissue
inflammation, and duration of viral shedding in dogs with experimentally induced
ocular CHV-1 infection.
PMID- 29943640
TI - Antinociceptive efficacy and respiratory effects of dexmedetomidine in ball
pythons (Python regius).
AB - OBJECTIVE To determine antinociceptive efficacy, behavioral patterns, and
respiratory effects associated with dexmedetomidine administration in ball
pythons (Python regius). ANIMALS 12 ball pythons. PROCEDURES Antinociception was
assessed by applying an infrared heat stimulus to the cranioventral surface of
snakes during 2 experiments. Thermal withdrawal latency was measured at 0, 2, and
24 hours after SC injections of dexmedetomidine (0.1 or 0.2 mg/kg) or saline
(0.9% NaCl) solution and at 0 to 60 minutes after injection of dexmedetomidine
(0.1 mg/kg) or saline solution. Behaviors were recorded at 0, 2, and 24 hours
after administration of dexmedetomidine (0.1 mg/kg) or saline solution. Tongue
flicking, head flinch to the approach of an observer's hand, movement, and
righting reflex were scored. Respiratory frequency was measured by use of
plethysmography to detect breathing-related movements after injection of
dexmedetomidine (0.1 mg/kg) or saline solution. RESULTS Mean baseline withdrawal
latency was 5 to 7 seconds; saline solution did not alter withdrawal latency.
Dexmedetomidine increased withdrawal latency by 18 seconds (0.2 mg/kg) and 13
seconds (0.1 mg/kg) above baseline values at 2 hours. Increased withdrawal
latency was detected within 15 minutes after dexmedetomidine administration. At 2
hours after injection, there were few differences in behavioral scores.
Dexmedetomidine injection depressed respiratory frequency by 55% to 70%, compared
with results for saline solution, but snakes continued to breathe without
prolonged apnea. CONCLUSIONS AND CLINICAL RELEVANCE Dexmedetomidine increased
noxious thermal withdrawal latency without causing excessive sedation. Therefore,
dexmedetomidine may be a useful analgesic drug in ball pythons and other snake
species.
PMID- 29943641
TI - Involvement of LIMK1/2 in actin assembly during mouse embryo development.
AB - LIMKs (LIMK1 and LIMK2) are serine/threonine protein kinases that involve in
various cellular activities such as cell migration, morphogenesis and
cytokinesis. However, its roles during mammalian early embryo development are
still unclear. In the present study, we disrupted LIMK1/2 activity to explore the
functions of LIMK1/2 during mouse early embryo development. We found that p
LIMK1/2 mainly located at the cortex of each blastomeres from 2-cell to 8-cell
stage, and p-LIMK1/2 also expressed at morula and blastocyst stage in mouse
embryos. Inhibition of LIMK1/2 activity by LIMKi 3 (BMS-5) at the zygote stage
caused the failure of embryo early cleavage, and the disruption of LIMK1/2
activity at 8-cell stage caused the defects of embryo compaction and blastocyst
formation. Fluorescence staining and intensity analysis results demonstrated that
the inhibition of LIMK1/2 activity caused aberrant cortex actin expression and
the decrease of phosphorylated cofilin in mouse embryos. Taken together, we
identified LIMK1/2 as an important regulator for cofilin phosphorylation and
actin assembly during mouse early embryo development.
PMID- 29943643
TI - Editorial Comment on: Prediction of Bacteriuria Based on Clinical or Laboratory
Parameters in Patients with Indwelling Ureteral Stents Before Ureterorenoscopy
Should Not Substitute for Urine Cultures by Weber et al.
PMID- 29943642
TI - A new baby in the c-Myc-directed transcriptional machinery: Che-1/AATF.
AB - B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common
malignancy in childhood. Despite the high cure-rate, identifying new druggable
molecular targets is still of great interest. In a cohort of BCP-ALL pediatric
patients, irrespectively of the molecule/karyotype lesions found, we recently
observed high expression of c-Myc and Che-1/AATF, which disappears at time of
remission. Study of the molecular mechanisms involved in this co-expression
revealed that Che-1 expression was crucial for induction of blast-cell
proliferation driven by c-Myc. Furthermore, Che-1/AATF silencing in primary BCP
ALL cell lines improves responsiveness to chemotherapy. These data individuate
Che-1 as a possible novel target in the treatment of BCP-ALL able to affect c-Myc
driven tumorigenicity.
PMID- 29943644
TI - The RANKL rs12585014 polymorphism is associated with age at menarche in
postmenopausal women with hip fracture.
AB - The RANK/RANKL/OPG signaling is important in the regulation of bone turnover. The
aim of the present work was to analyze the rs3018362 and rs12585014 polymorphisms
in the RANK and RANKL genes, as well as risk factors in postmenopausal women.
Women with hip fracture, with femoral neck osteoporosis and controls (n = 646)
were recruited. From these, 303 women who fulfill the inclusion criteria were
genotyped using real-time PCR with TaqMan probes. There were no associations of
the rs3018362 and rs12585014 with osteoporosis or fracture. When women were
divided by age at menarche, the rs12585014 GG genotype was strongly associated
with age at menarche >13 years [p = .00774, OR = 6.429 (1.907-21.103)] in women
with hip fracture. Significant differences in risk factors such as body mass
index, age at menopause, use of estrogens, the presence of hypertension, and
diabetes mellitus were found. Carrying the GG genotype of rs12585014 entails a
higher risk of having menarche later (>13 years), which could involves a greater
risk of fractures. The rs3018362 and rs12585014 do not seem to be associated with
hip osteoporosis or hip fracture in Mexican women.
PMID- 29943645
TI - Challenges with the precise prediction of ABC-transporter interactions for
improved drug discovery.
AB - INTRODUCTION: Given that membrane efflux transporters can influence a drug's
pharmacokinetics, efficacy and safety, identifying potential substrates and
inhibitors of these transporters is a critical element in the drug discovery and
development process. Additionally, it is important to predict the inhibition
potential of new drugs to avoid clinically significant drug interactions. The
goal of preclinical studies is to characterize a new drug as a substrate or
inhibitor of efflux transporters. Areas covered: This article reviews preclinical
systems that are routinely utilized to determine whether a new drug is substrate
or inhibitor of efflux transporters including in silico models, in vitro membrane
and cell assays, and animal models. Also included is an examination of studies
comparing in vitro inhibition data to clinical drug interaction outcomes. Expert
opinion: While a number of models are employed to classify a drug as an efflux
substrate or inhibitor, there are challenges in predicting clinical drug
interactions. Improvements could be made in these predictions through a tier
approach to classify new drugs, validation of preclinical assays, and refinement
of threshold criteria for clinical interaction studies.
PMID- 29943646
TI - A fatal workplace nickel carbonyl exposure.
PMID- 29943647
TI - Evaluation of a mobile social networking application for improving diabetes Type
2 knowledge: an intervention study using WhatsApp.
AB - AIM: The aim of this study is to evaluate the WhatsApp social networking
application for improving knowledge, self-efficacy and awareness about diabetes
management. METHODOLOGY: The study was conducted with intervention and control
groups at Teaching Hospital in Al-Khobar, Saudi Arabia. The intervention group
received weekly educational messages using WhatsApp, while the control group
received regular care. RESULTS: Statistically, compared with the control group,
the diabetes knowledge and self-efficacy of the intervention group increased
significantly after the intervention with the WhatsApp application. CONCLUSION:
The WhatsApp application can be effectively used for enhancing diabetes
knowledge, self-efficacy and awareness among the Saudi population.
PMID- 29943648
TI - Orbito-cranial gunshot injury: the case of the missing entrance wound.
AB - This paper presents the case of a 68 years old male who was admitted to the
hospital after being attacked by another person. The main clinical signs were
confusion and severe periorbital edema, findings of gunshot injury were not
evident initially. However, a CT scan showed findings compatible with an orbito
cranial perforating gunshot injury. To the best of the author's knowledge, cases
like this have not been reported in the literature. This report shows us that an
orbito-cranial gunshot injury should be ruled out in cases of severe periorbital
edema, especially if the cause of the injury remains unidentified.
PMID- 29943649
TI - Three-dimensional multimodality fusion imaging as an educational and planning
tool for deep-seated meningiomas.
AB - INTRODUCTION: The utility of surgical simulation with three-dimensional
multimodality fusion imaging (3D-MFI) has been demonstrated. However, its
potential in deep-seated brain lesions remains unknown. The aim of this study was
to investigate the impact of 3D-MFI in deep-seated meningioma operations.
MATERIAL AND METHODS: Fourteen patients with deeply located meningiomas were
included in this study. We constructed 3D-MFIs by fusing high-resolution magnetic
resonance (MR) and computed tomography (CT) images with a rotational digital
subtraction angiogram (DSA) in all patients. The surgical procedure was simulated
by 3D-MFI prior to operation. To assess the impact on neurosurgical education,
the objective values of surgical simulation by 3D-MFIs/virtual reality (VR) video
were evaluated. To validate the quality of 3D-MFIs, intraoperative findings were
compared. The identification rate (IR) and positive predictive value (PPV) for
the tumor feeding arteries and involved perforating arteries and veins were also
assessed for quality assessment of 3D-MFI. RESULTS: After surgical simulation by
3D-MFIs, near-total resection was achieved in 13 of 14 (92.9%) patients without
neurological complications. 3D-MFIs significantly contributed to the
understanding of surgical anatomy and optimal surgical view (p < .0001) and
learning how to preserve critical vessels (p < .0001) and resect tumors safety
and extensively (p < .0001) by neurosurgical residents/fellows. The IR of 3D-MFI
for tumor-feeding arteries and perforating arteries and veins was 100% and 92.9%,
respectively. The PPV of 3D-MFI for tumor-feeding arteries and perforating
arteries and veins was 98.8% and 76.5%, respectively. CONCLUSIONS: 3D-MFI
contributed to learn skull base meningioma surgery. Also, 3D-MFI provided high
quality to identify critical anatomical structures within or adjacent to deep
seated meningiomas. Thus, 3D-MFI is promising educational and surgical planning
tool for meningiomas in deep-seated regions.
PMID- 29943650
TI - Pharmacokinetics-pharmacodynamics of antifungal agents in the central nervous
system.
AB - INTRODUCTION: Mortality from invasive fungal disease involving the central
nervous system (CNS) is excessive. Achieving therapeutic drug concentrations at
the site of infection within the CNS is always difficult and its evaluation is
complex due to anatomical barriers and variable pathophysiological lesions. Areas
covered: This review provides an updated summary of the CNS PK of antifungal
therapies. It considers factors that influence the success of antifungal regimens
for CNS infection as well as preclinical and clinical data that quantify
antifungal pharmacokinetics (PK) in the CNS. Furthermore, it presents state-of
the-art technologies to enhance the clinical use of existing antifungal drugs,
and introduces novel antifungal drugs in development. Expert opinion: The
antifungal drugs currently available are either suboptimal, or are being used
suboptimally, for CNS disease. Therapeutic drug monitoring is mandatory to
enhance their effectiveness. Novel drugs in development may offer more
efficacious options. In all cases, contemporary technologies to assess CNS PK
offer the opportunity to enhance our understanding and use of antifungal drugs
for CNS fungal disease.
PMID- 29943652
TI - Autophagy in Human Health and Disease: Novel Therapeutic Opportunities.
AB - SIGNIFICANCE: In eukaryotes, autophagy represents a highly evolutionary conserved
process, through which macromolecules and cytoplasmic material are degraded into
lysosomes and recycled for biosynthetic or energetic purposes. Dysfunction of the
autophagic process has been associated with the onset and development of many
human chronic pathologies, such as cardiovascular, metabolic, and
neurodegenerative diseases as well as cancer. Recent Advances: Currently,
comprehensive research is being carried out to discover new therapeutic agents
that are able to modulate the autophagic process in vivo. Recent evidence has
shown that a large number of natural bioactive compounds are involved in the
regulation of autophagy by modulating several transcriptional factors and
signaling pathways. CRITICAL ISSUES: Critical issues that deserve particular
attention are the inadequate understanding of the complex role of autophagy in
disease pathogenesis, the limited availability of therapeutic drugs, and the lack
of clinical trials. In this context, the effects that natural bioactive compounds
exert on autophagic modulation should be clearly highlighted, since they depend
on the type and stage of the pathological conditions of diseases. FUTURE
DIRECTIONS: Research efforts should now focus on understanding the survival
supporting and death-promoting roles of autophagy, how natural compounds interact
exactly with the autophagic targets so as to induce or inhibit autophagy and on
the evaluation of their pharmacological effects in a more in-depth and
mechanistic way. In addition, clinical studies on autophagy-inducing natural
products are strongly encouraged, also to highlight some fundamental aspects,
such as the dose, the duration, and the possible synergistic action of these
compounds with conventional therapy. Antioxid. Redox Signal. 00, 000-000.
PMID- 29943651
TI - Localized co-delivery of collagenase and trastuzumab by thermosensitive hydrogels
for enhanced antitumor efficacy in human breast xenograft.
AB - Modulation of the collagen-rich extracellular matrix (ECM) in solid tumors by the
treatment with collagenase has been proved effective in enhancement of the
interstitial transport and antitumor efficacy of antibodies. We, therefore,
developed a PLGA-PEG-PLGA polymer-based thermosensitive hydrogel, which
incorporated a HER2-targeted monoclonal antibody trastuzumab and collagenase
(Col/Tra/Gel) for peritumoral administration. HER2-positvie BT474 tumor-bearing
mice were selected as a model. The Col/Tra/Gel showed the continuous and biphasic
release of protein drugs for 9 days in vitro. NIR imaging studies demonstrated a
long-term retention of Col/Tra/Gel hydrogel in the peritumoral area for over 20
days. Treatment with Col/Tra/Gel reduced the collagen density and enhanced
apoptotic cell death in tumor tissue, resulting in superior treatments with
increased efficacy and reduced toxicity compared with other control groups.
Moreover, a quarter-dose of Col/Tra/Gel exhibited a better antitumor efficacy
than that of intravenous injection of clinical trastuzumab formulation. This
localized co-delivery system offers a potential strategy for the modulation of
dense ECM and enhancement of antibody efficacy.
PMID- 29943653
TI - Improving Clinical Prediction Rules In Acute Kidney Injury With The Use of
Biomarkers of Cell Cycle Arrest: A Pilot Study.
AB - INTRODUCTION: Early recognition of patients developing acute kidney injury is of
considerable interest, we report the first use of a combination of a clinical
prediction rule with a biomarker in emergent adult medical patients to improve
AKI recognition. METHODS: Single-centre prospective pilot study of medical
admissions without AKI identified as high risk by a clinical prediction rule.
Urine samples were obtained and tissue inhibitor of metalloproteinases-2 (TIMP-2)
and insulin-like growth factor binding protein 7 (IGFBP7) - biomarkers associated
with cell cycle arrest, were measured. OUTCOME: Creatinine based KDIGO hospital
acquired AKI (HA-AKI). RESULTS: Of 69 patients recruited, HA-AKI developed in 13%
(n = 9), in whom biomarker values were higher (median 0.43 [interquartile range
0.21-1.25] vs. 0.07 [0.03-0.16] in cases without (P = 0.008). Peak rise in
creatinine was higher in biomarker positive cases (median 30 MUmol/l (7-72) vs 1
MUmol/l (0-16), P = 0.002). AUROC was 0.78 (95% CI 0.57-0.98). At the suggested
cut-off (0.3) sensitivity for predicting AKI was 78% (95% CI 40-97%), specificity
89% (78-95%), positive predictive value 50% (31-69%) and negative predictive
value 96% (89-99%). DISCUSSION: Addition of a urinary biomarker allows exclusion
of a significant number of patients identified to be at higher risk of AKI by a
clinical prediction rule.
PMID- 29943654
TI - Reexamining performance validity cutoffs within the Complex Ideational Material
and the Boston Naming Test-Short Form using an experimental malingering paradigm.
AB - OBJECTIVE: This study was designed to cross-validate previously published
performance validity cutoffs embedded within the Complex Ideational Material
(CIM) and the Boston Naming Test-Short Form (BNT-15). METHOD: Seventy healthy
undergraduate students were randomly assigned to either a control condition (n =
40) and instructed to perform to the best of their ability or an experimental
malingering (n = 30) condition and instructed to feign cognitive impairment while
avoiding detection. All participants were administered the same battery of
neuropsychological tests. RESULTS: Previously published validity cutoffs within
the CIM (raw score <=9 or T-score <=29) and BNT-15 (<=12) produced good
classification accuracy using both experimental malingering and psychometrically
defined invalid responding as criterion variable. However, a BNT-15 completion
time >=85 s produced a better signal detection profile than BNT-15 accuracy
scores. CONCLUSIONS: Results support the clinical utility of existing cutoffs.
Given the relatively high base rate of failure even in the control group (5-15%),
and the perfect specificity of CIM <=9 and BNT-15 <= 11 to noncredible
responding, relabeling this range of performance as "Abnormal" instead of
"Impaired" would better capture the uncertainty in its clinical interpretation.
PMID- 29943655
TI - Exploiting Viruses to Treat Diseases.
PMID- 29943656
TI - The Impact of Cervical Spinal Cord Contusion on the Laryngeal Resistance in the
Rat.
AB - The present study was designed to investigate laryngeal function responses to
chemoreceptor activation after unilateral high-cervical spinal cord contusion in
rats. Adult male Sprague-Dawley rats received laminectomy or unilateral contusion
at the C2 spinal cord. Both respiratory airflow and subglottal pressure were
measured in spontaneously breathing rats at three days, two weeks, or six weeks
after spinal surgery. Laryngeal closure responses were evoked via intrajugular
capsaicin (1.5 MUg/kg) administration and hypoxia (12.5% O2, 3 min) to activate
bronchopulmonary C-fibers and chemoreceptors, respectively. High cervical
contusion resulted in long-term reductions in tidal volume without changes in
laryngeal resistance at baseline. Alternatively, capsaicin-induced increased
subglottal pressure was significantly attenuated in contused rats at three days
post-injury. Contused rats regained the ability to increase laryngeal resistance
after capsaicin treatment at two and six weeks post-injury, whereas this
recovered response remained weaker than uninjured animals. Notably, hypoxia
induced laryngeal closure was not altered during the acute injured stage, but
instead was blunted at six weeks post-injury. These data suggest that cervical
spinal cord injury not only influences the breathing pattern, but it also impacts
upper airway function through modulation of laryngeal resistance. An attenuated
laryngeal closure response may negatively impact the ability to prevent irritant
inhalation and maintenance of the functional residual capacity. This may
contribute to the provocation of pulmonary disease after cervical spinal cord
injury.
PMID- 29943657
TI - Predictors of Rectourethral Fistula Formation After Primary Whole-Gland
Cryoablation for Prostate Cancer: Results from the Cryo On-Line Database
Registry.
AB - PURPOSE: To define the incidence and risk factors associated with rectourethral
fistula (RUF) formation following primary whole-gland cryosurgery using a
multicenter centralized registry. PATIENTS AND METHODS: The Cryo On-Line Data
(COLD) registry was queried for men undergoing primary whole-gland cryotherapy
between 1990 and 2014 who developed a RUF. Patient factors and disease parameters
were correlated with RUF using chi-square and the t-test. Variables with p < 0.25
were entered into a binary logistic regression with stepwise backward elimination
to determine the factors associated with RUF formation. RESULTS: A total of 4102
men underwent primary whole-gland cryotherapy in the COLD registry at the time of
analysis. Postoperative RUF was documented in 50 out of 4102 cases (1.2%).
Patients with RUF had similar demographic data, prostate volume, preoperative
prostate-specific antigen level, and clinical stage in comparison to those
without fistula. On both univariate and multivariate analyses, postoperative
urinary retention (odds ratio [OR]: 6.30; confidence interval [95% CI] 3.43
11.58, p < 0.001), preoperative Gleason score of >=7 (OR: 1.92; 95% CI 1.08-3.43,
p = 0.027), and preoperative incontinence (OR: 2.95; 95% CI 1.12-7.76, p = 0.028)
were the most significant risk factors associated with RUF formation. CONCLUSION:
Primary whole-gland cryotherapy for prostate cancer is associated with a
historically low rate (1.2%) of postoperative RUF formation. The rate decreased
further to 0.55% over the last several years, suggesting better patient selection
and technical improvement. Postoperative urinary retention, Gleason score >=7,
and preoperative urinary incontinence were the key demographic, clinical, and
pathologic features associated with RUF formation in this study.
PMID- 29943659
TI - Frozen Sections for Margins During Partial Nephrectomy Do Not Influence
Recurrence Rates.
AB - INTRODUCTION: Frozen sections (FS) are routinely employed to assess margin status
during partial nephrectomy (PN) for clinically localized renal cell carcinoma
(CLRCC); however, their oncologic benefit remains unclear. There have been no
studies investigating the long-term impact of FS on local or metastatic
recurrence. We wished to determine whether the utilization of FS for this purpose
during PN influenced recurrence rates. MATERIALS AND METHODS: We performed a
retrospective review of 1090 patients with (n = 172) and without (n = 918) FS
during open and robotic PN between 2006 and 2016 for CLRCC at a single tertiary
care institution. Standard follow-up protocols were employed, with imaging used
to guide subsequent biopsy for confirmation. Univariate and multivariate
competing-risk regression analysis predicting the association of FS status and
clinicodemographic characteristics with recurrence, with adjustment for all-cause
mortality, were performed. Administrative data were reviewed to calculate costs
of FS. RESULTS: Forty-five out of 1090 (4.13%) patients had recurrence. There was
no difference in the cumulative incidence of recurrence between patients with and
without FS (chi2 = 0.001, p = 0.97). On multivariable competing risk analysis, FS
was not associated with recurrence (hazard ratio [HR], 1.56; 95% confidence
interval [CI], 0.65-3.76). However, tumor grade (g3-4 vs 1-2: HR, 2.45; 95% CI,
1.16-5.14) and stage (>pT2 vs pT1a: HR, 2.86; 95% CI, 1.13-7.26) were associated
with recurrence. The average direct charge per patient undergoing FS was $902.
CONCLUSIONS: Intraoperative FS for margins during PN did not predict decreased
recurrence rates in a single-institution high-volume center. Given the lack of
associated benefit, and the added cost, the utilization of FS during PN should be
limited.
PMID- 29943658
TI - Nucleolin modulates compartmentalization and dynamics of histone 2B-ECFP in the
nucleolus.
AB - Eukaryotic cells have 2 to 3 discrete nucleoli required for ribosome synthesis.
Nucleoli are phase separated nuclear sub-organelles. Here we examined the role of
nuclear Lamins and nucleolar factors in modulating the compartmentalization and
dynamics of histone 2B (H2B-ECFP) in the nucleolus. Live imaging and Fluorescence
Recovery After Photobleaching (FRAP) of labelled H2B, showed that the depletion
of Lamin B1, Fibrillarin (FBL) or Nucleostemin (GNL3), enhances H2B-ECFP mobility
in the nucleolus. Furthermore, Nucleolin knockdown significantly decreases H2B
ECFP compartmentalization in the nucleolus, while H2B-ECFP residence and mobility
in the nucleolus was prolonged upon Nucleolin overexpression. Co-expression of N
terminal and RNA binding domain (RBD) deletion mutants of Nucleolin or inhibiting
45S rRNA synthesis reduces the sequestration of H2B-ECFP in the nucleolus. Taken
together, these studies reveal a crucial role of Nucleolin-rRNA complex in
modulating the compartmentalization, stability and dynamics of H2B within the
nucleolus.
PMID- 29943660
TI - Methods used to assess the performance of biomarkers for the diagnosis of acute
kidney injury: a systematic review and meta-analysis.
AB - PURPOSE: Methods used to explore biomarkers for acute kidney injury (AKI) might
have a major impact on the results and the use of these biomarkers. We evaluated
the methods used to investigate biomarkers of AKI. MATERIALS AND METHODS: A
systematic review and meta-analysis were performed using a computerized search of
the MEDLINE and the EMBASE databases (PROSPERO CRD42017059618). Articles
reporting biomarker's performance to diagnose AKI were included. The outcome
included a description of the methods used to assess the performance of
biomarkers to diagnose AKI. RESULTS: Among the 295 included studies, assessment
of biomarkers was the primary endpoint in 284 with sample size calculation in
only 8% of cases. Eighty-five percent of the studies summarized the performance
of biomarkers with receiver operating characteristic (ROC) curves; however, 74
studies (25%) did not provide the threshold, sensibility or specificity. A total
of 176 studies evaluated more than one biomarker, and only 25% combined
biomarkers to increase diagnostic performance. We determined that the definition
of AKI and study design impacted the diagnostic performance using uNGAL (urinary
neutrophil gelatinase-associated lipocalin) as an example. Major publication bias
was identified. CONCLUSIONS: Most articles that reported biomarkers of AKI
performance present methodological weaknesses. Basic rules should be provided to
increase the quality of reporting in this area.
PMID- 29943661
TI - Engineered Nanoparticles for Effective Redox Signaling During Angiogenic and
Antiangiogenic Therapy.
AB - SIGNIFICANCE: Redox signaling plays a vital role in regulating various cellular
signaling pathways and disease biology. Recently, nanomedicine (application of
nanotechnology in biology and medicine) has been demonstrated to regulate
angiogenesis through redox signaling. A complete understanding of redox signaling
pathways influenced angiogenesis/antiangiogenesis triggered by therapeutic
nanoparticles is extensively reviewed in this article. Recent Advances: In recent
times, nanomedicines are regarded as the Trojan horses that could be employed for
successful drug delivery, gene delivery, peptide delivery, disease diagnosis, and
others, conquering barriers associated with conventional theranostic approaches.
CRITICAL ISSUES: Physiological angiogenesis is a tightly regulated process
maintaining a balance between proangiogenic and antiangiogenic factors. The redox
signaling is one of the main factors that contribute to this physiological
balance. An aberrant redox signaling cascade can be caused by several exogenous
and endogenous factors and leads to reduced or augmented angiogenesis that
ultimately results in several disease conditions. FUTURE DIRECTIONS: Redox
signaling-based nanomedicine approach has emerged as a new platform for
angiogenesis-related disease therapy, where nanoparticles promote angiogenesis
via controlled reactive oxygen species (ROS) production and antiangiogenesis by
triggering excessive ROS formation. Recently, investigators have identified
different efficient nano-candidates, which modulate angiogenesis by controlling
intracellular redox molecules. Considering the importance of angiogenesis in
healthcare, a thorough understanding of nanomedicine-regulated redox signaling
would inspire researchers to design and develop more novel nanomaterials that
could be used as an alternative strategy for the treatment of various diseases,
where angiogenesis plays a vital role. Antioxid. Redox Signal. 00, 000-000.
PMID- 29943662
TI - Let's Get to the Point: Comparing Insertion Characteristics and Scope Damage of
Flat-Tip and Ball-Tip Holmium Laser Fibers.
AB - INTRODUCTION: A ball-tip holmium laser fiber (TracTip; Boston Scientific) has
been developed to theoretically reduce damaging friction forces generated within
a ureteroscope working channel. We compared the insertional forces and damage
with a ureteroscope inner lining when inserting standard flat-tip and ball-tip
laser fibers. MATERIALS AND METHODS: A standard ureteroscope channel liner was
placed in a 3D-printed plastic mold. Molds were created at four angles of
deflection (30 degrees , 45 degrees , 90 degrees , and 180 degrees ) with a 1 cm
radius of curvature. New 200 MUm ball-tip (TracTip; Boston Scientific) and 200
MUm flat-tip (Flexiva; Boston Scientific) laser fibers were advanced through the
liner using a stage controller. A strain gauge was used to measure force required
for insertion. Each fiber was passed 600 times at each angle of deflection. The
ureteroscope liner was changed every 150 passes. Leak testing was performed every
50 passes or when the insertional force increased significantly to assess damage
to the liner. RESULTS: At all deflection angles, the average insertional force
was significantly lower with the ball-tip laser fibers compared with flat-tip
laser fibers (p < 0.001). All trials with the ball-tip lasers were completed at
each angle without any leaks. Two of four trials using flat-tip fibers at 45
degrees deflection caused liner leaks (at 91 and 114 passes). At 90 degrees
deflection, all flat-tip trials caused liner leaks on first pass. The 180 degrees
trials could not physically be completed with the flat-tip laser fiber. Within
the flat- and ball-tip groups, an increasing amount of force was needed to pass
the fiber as the degree of deflection increased (p < 0.001). CONCLUSIONS: The
ball-tip holmium laser fiber can be safely passed through a deflected
ureteroscope without causing liner perforation. The standard flat-tip fiber
requires greater insertion force at all angles and can cause the ureteroscope
liner to leak if it is deflected 45 degrees or more.
PMID- 29943664
TI - Assessing Cost of Robotic Utilization in Partial Nephrectomy with Increasing
Utilization.
AB - PURPOSE: To evaluate trends in utilization of robotic assistance in partial
nephrectomy (PN) and assess the association between cost and utilization.
PATIENTS AND METHODS: Using the 2009-2012 Nationwide Inpatient Sample database,
we identified all adult (>17 years) patients undergoing PN for localized primary
renal malignancy. Coding for robotic assistance (17.4 * ) began in the final
quarter of 2008. The primary outcome was total hospital cost exclusive of
physician fees. A multiple linear regression model was used to adjust for patient
and hospital characteristics. RESULTS: Between 2009 and 2012, there were 32,664
(58%) open, 3498 (6%) laparoscopic, and 20,350 (36%) robot-assisted partial
nephrectomies performed in the United States. Between 2009 and 2012, the total
number of partial nephrectomies semiannually increased by 93% (5114-9845) with
robotic partial nephrectomies (RPNs) representing >80% of the increase. RPN
increased from 1029 cases in the first half of 2009 to 4840 in the last half of
2012 and surpassed utilization of open nephrectomy. The proportion of all partial
nephrectomies performed with robotic assistance increased from 20% to 49% during
the same period. After adjusting for demographics, Charlson comorbidity index,
and hospital region, RPN went from $1,464 (p = 0.009) more than open in 2009 to
$456 (p = 0.28) less than open in 2012. CONCLUSIONS: Utilization of RPN surpassed
open in 2012 in the United States. The difference in cost between the robotic and
open approaches decreased during the study period and by 2011 was not
statistically different.
PMID- 29943663
TI - Chronic social stress induces DNA methylation changes at an evolutionary
conserved intergenic region in chromosome X.
AB - Chronic stress resulting from prolonged exposure to negative life events
increases the risk of mood and anxiety disorders. Although chronic stress can
change gene expression relevant for behavior, molecular regulators of this change
have not been fully determined. One process that could play a role is DNA
methylation, an epigenetic process whereby a methyl group is added onto
nucleotides, predominantly cytosine in the CpG context, and which can be induced
by chronic stress. It is unknown to what extent chronic social defeat, a model of
human social stress, influences DNA methylation patterns across the genome. Our
study addressed this question by using a targeted-capture approach called Methyl
Seq to investigate DNA methylation patterns of the dentate gyrus at putative
regulatory regions across the mouse genome from mice exposed to 14 days of social
defeat. Findings were replicated in independent cohorts by bisulfite
pyrosequencing. Two differentially methylated regions (DMRs) were identified. One
DMR was located at intron 9 of Drosha, and it showed reduced methylation in
stressed mice. This observation replicated in one of two independent cohorts. A
second DMR was identified at an intergenic region of chromosome X, and
methylation in this region was increased in stressed mice. This methylation
difference replicated in two independent cohorts and in Major Depressive Disorder
(MDD) postmortem brains. These results highlight a region not previously known to
be differentially methylated by chronic social defeat stress and which may be
involved in MDD.
PMID- 29943665
TI - Application of automatic statistical post-processing method for analysis of
ultrasonic and digital dermatoscopy images.
AB - Ultrasonic and digital dermatoscopy diagnostic methods are used in order to
estimate the changes of structure, as well as to non-invasively measure the
changes of parameters of lesions of human tissue. These days, it is very actual
to perform the quantitative analysis of medical data, which allows to achieve the
reliable early-stage diagnosis of lesions and help to save more lives. The
proposed automatic statistical post-processing method based on integration of
ultrasonic and digital dermatoscopy measurements is intended to estimate the
parameters of malignant tumours, measure spatial dimensions (e.g. thickness) and
shape, and perform faster diagnostics by increasing the accuracy of tumours
differentiation. It leads to optimization of time-consuming analysis procedures
of medical images and could be used as a reliable decision support tool in the
field of dermatology.
PMID- 29943667
TI - Rapamycin Confers Neuroprotection Against Aging-Induced Oxidative Stress,
Mitochondrial Dysfunction, and Neurodegeneration in Old Rats Through Activation
of Autophagy.
AB - Brain aging is an intricate and natural phenomenon exclusively characterized by
oxidative stress, accumulation of oxidatively damaged macromolecules, and
alterations in structure and function of neurons that further increase the risk
factor for most of the neurodegenerative diseases. In addition, age-dependent
defective autophagy has also been implicated to favor the pathogenesis and
prevalence of the neurological diseases. Therefore, the development of strategies
that delay aging and the concomitant neurological disorders remain elusive. Thus,
the present study was undertaken to investigate the effect of rapamycin-induced
activation of autophagy on aging-related oxidative stress, cell death,
neuroinflammation, and neurodegeneration in rat brain. Our data demonstrated the
significant age-related oxidative stress, apoptotic cell death, elevated
inflammatory response, and reduced level of markers associated with rejuvenation
and neural integrity, including the activities of ion channel transporters
(Na+/K+-ATPase and Ca2+-ATPase) and acetylcholinesterase in the brain of old aged
rats. Furthermore, rapamycin (0.5 mg/kg b.w. for 28 days) induced activation of
autophagy provided significant protection to aging rat brain by reducing the
aging-induced oxidative stress, apoptotic cell death, and markers of
neurodegeneration. Thus, our data confirmed that autophagy plays a pivotal role
in delaying brain aging plausibly by maintaining the cellular homeostasis, and
structural and functional integrity of cells in the brain.
PMID- 29943668
TI - Spontaneous migration of retained intracranial bullet.
PMID- 29943666
TI - Recurrent Glioblastoma Treated with Recombinant Poliovirus.
AB - BACKGROUND: The prognosis of patients with recurrent World Health Organization
(WHO) grade IV malignant glioma is dismal, and there is currently no effective
therapy. We conducted a dose-finding and toxicity study in this population of
patients, evaluating convection-enhanced, intratumoral delivery of the
recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO). PVSRIPO recognizes
the poliovirus receptor CD155, which is widely expressed in neoplastic cells of
solid tumors and in major components of the tumor microenvironment. METHODS: We
enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV
malignant glioma, confirmed on histopathological testing, with measurable disease
(contrast-enhancing tumor of >=1 cm and <=5.5 cm in the greatest dimension). The
study evaluated seven doses, ranging between 107 and 1010 50% tissue-culture
infectious doses (TCID50), first in a dose-escalation phase and then in a dose
expansion phase. RESULTS: From May 2012 through May 2017, a total of 61 patients
were enrolled and received a dose of PVSRIPO. Dose level -1 (5.0*107 TCID50) was
identified as the phase 2 dose. One dose-limiting toxic effect was observed; a
patient in whom dose level 5 (1010 TCID50) was administered had a grade 4
intracranial hemorrhage immediately after the catheter was removed. To mitigate
locoregional inflammation of the infused tumor with prolonged glucocorticoid use,
dose level 5 was deescalated to reach the phase 2 dose. In the dose-expansion
phase, 19% of the patients had a PVSRIPO-related adverse event of grade 3 or
higher. Overall survival among the patients who received PVSRIPO reached a
plateau of 21% (95% confidence interval, 11 to 33) at 24 months that was
sustained at 36 months. CONCLUSIONS: Intratumoral infusion of PVSRIPO in patients
with recurrent WHO grade IV malignant glioma confirmed the absence of
neurovirulent potential. The survival rate among patients who received PVSRIPO
immunotherapy was higher at 24 and 36 months than the rate among historical
controls. (Funded by the Brain Tumor Research Charity and others;
ClinicalTrials.gov number, NCT01491893 .).
PMID- 29943669
TI - Perinephric Fat Stranding Is Associated with Elevated Creatinine Among Patients
with Acutely Obstructing Ureterolithiasis.
AB - INTRODUCTION: Pyelovenous/pyelolymphatic backflow from acute ureteral
obstruction, manifesting radiologically as perinephric fat stranding (PFS), may
result in elevated serum creatinine. Among patients with acutely obstructing
ureterolithiasis, we evaluated the relationship between degree of PFS and changes
in serum creatinine from baseline. METHODS: Our tertiary care center's radiology
dictation system (Fluency Discovery, M Modal) was queried for noncontrast
abdominopelvic CT studies obtained in the Emergency Department for patients with
obstructing ureteral calculi from 7/2015 to 4/2016. A single radiologist blinded
to clinical data reviewed all CT scans and coded stone size, location, severity
of hydronephrosis, and degree of PFS (none, mild, moderate, severe). For patients
who met imaging criteria, a retrospective chart review was performed. RESULTS: We
evaluated 148 patients with mean age of 46 years (SD 14.6), 56.0% (n = 83) were
male. On univariate analysis, moderate-severe perinephric stranding was
associated with elevated creatinine from baseline (OR 2.93, p = 0.03). Mean
creatinine increased as the severity of stranding increased (none Cr = 0.978
mg/dL, mild Cr = 0.983 mg/dL, moderate Cr = 1.165 mg/dL, severe Cr = 1.370 mg/dL;
p < 0.01). An increase in creatinine from baseline was not associated with
greater severity of hydronephrosis (OR 0.504, p = 0.189). There was no
association between degree of PFS and severity of hydronephrosis, positive urine
culture, stone location, or symptom duration (p > 0.05). On regression analysis
controlling for positive urine culture and degree of hydronephrosis, there
remained an association between elevated serum creatinine from baseline and
moderate-severe PFS (OR 9.0, p = 0.01). CONCLUSIONS: Among patients with acute
obstructive ureterolithiasis, moderate-severe PFS was associated with elevated
serum creatinine from baseline. This elevated creatinine was not explained by the
obstructed kidney alone, as there was no association between the severity of
hydronephrosis and increased creatinine. Pyelovenous/pyelolymphatic backflow
resulting in PFS may be a contributing factor to elevated serum creatinine in
this setting.
PMID- 29943670
TI - Beyond 'charting outcomes' in the radiation oncology match: analysis of self
reported applicant data.
AB - The Charting Outcomes resource is useful in gauging an applicant's competiveness
for a given specialty. However, many variables are not reported in Charting
Outcomes that may influence an applicant's ability to match. A significant
proportion of applicants record their experiences in an anonymous, self-reported
applicant spreadsheet. We analyzed factors associated with a successful match
using this dataset to test the hypothesis that research productivity and high
academic performance correlates with success rates. A retrospective analysis of
"RadOnc Interview Spreadsheet" for the 2015, 2016, and 2017 radiation oncology
match was performed. Data were accessed via studentdoctor.net. Board scores,
research characteristics, Sub-I participation, and interview invitation rates
were available. Mann-Whitney U, Kruskal-Wallis, and chi-square tests were used
for statistical analysis. When possible, results were compared to those reported
in the National Residency Match Program's "Charting Outcomes" report. A total of
158 applicants were examined for the applicant characteristics. Applicants
applied to a median of 61 programs and received a median of 14 interviews. The
mean step 1 score was 248 (range: 198 to 272) and most were in the highest grade
point average quartile (68.3%). 21.7% participated in additional research
year(s), and 19% obtained a PhD. The majority of applicants took three radiation
oncology electives (48.7%). On multivariate analysis, alpha-omega-alpha (AOA)
honors society status (p=0.033), participating in a research year (p=0.001) and
number of journal publications (p=0.047) significantly correlated with higher
interview invitation rates. In summary, this study identifies important
considerations for radiation oncology applicants that have not been previously
reported, such as induction into AOA and number of journal publications.
PMID- 29943671
TI - Cigarette smoking and risk of Behcet's disease: a propensity score matching
analysis.
AB - OBJECTIVE: Behcet's disease (BD) is an inflammatory disease and smoking may have
a role in its triggering. This case-control study was conducted to investigate
the association between smoking and the risk of BD. METHODS: We included 192
patients with BD and 822 healthy siblings of patient with BD and 373 healthy
unrelated persons as control groups. Demographic data and smoking history of
patients and their siblings were obtained by direct and in some cases by
telephone interview with the participants. Demographic data and smoking history
of healthy controls were obtained by direct interview. Propensity score matching
(PSM) analyses for reducing the heterogeneity between studied groups and
calculating the actual effect of smoking in BD was performed. Matching was
performed based on demographic characteristics (age, gender, educational status
and marital status). After PSM, we carried out multivariate analyses with BD as
the main outcome variable and smoking history as the main predictor variable to
calculate odds ratios with 95% confidence intervals. RESULTS: Ever smoking was
not significantly associated with an increased risk of BD compared with never
smoking. In comparison with healthy siblings and healthy unrelated persons, the
relative risk of developing BD was 0.8-2.6. No significant differences were
observed in the clinical manifestations of BD patients in ever smokers and never
smokers. However, disease activity in ever smokers at disease presentation was
significantly more than never smokers. CONCLUSION: Smoking is not a significant
risk factor for BD.
PMID- 29943672
TI - Enhanced Voluntary Exercise Improves Functional Recovery following Spinal Cord
Injury by Impacting the Local Neuroglial Injury Response and Supporting the
Rewiring of Supraspinal Circuits.
AB - Recent reports suggest that rehabilitation measures that increase physical
activity of patients can improve functional outcome after incomplete spinal cord
injuries (iSCI). To investigate the structural basis of exercise-induced
recovery, we examined local and remote consequences of voluntary wheel training
in spinal cord injured female mice. In particular, we explored how enhanced
voluntary exercise influences the neuronal and glial response at the lesion site
as well as the rewiring of supraspinal tracts after iSCI. We chose voluntary
exercise initiated by providing mice with free access to running wheels over
"forced overuse" paradigms because the latter, at least in some cases, can lead
to worsening of functional outcomes after SCI. Our results show that mice
extensively use their running wheels not only before but also after injury
reaching their pre-lesion exercise levels within five days after injury. Enhanced
voluntary exercise improved their overall and skilled motor function after
injury. In addition, exercising mice started to recover earlier and reached
better sustained performance levels. These improvements in motor performance are
accompanied by early changes of axonal and glial response at the lesion site and
persistent enhancements of the rewiring of supraspinal connections that resulted
in a strengthening of both indirect and direct inputs to lumbar motoneurons.
PMID- 29943673
TI - A Prospective Observational Study of Complications in 140 Sialendoscopies.
AB - Objectives To evaluate the incidence and nature of complications associated with
diagnostic and interventional sialendoscopies and to report intervention failures
in a prospective setup. Study Design Prospective observational study. Setting
Academic tertiary care university hospital. Subjects and Methods Patients who
underwent diagnostic or interventional sialendoscopy between October 2015 and
December 2016 were prospectively enrolled. Patient data, operation-related
factors, treatment failures, and complications were recorded into a database and
analyzed. Results A total of 140 sialendoscopies were attempted or performed on
118 patients; 67 (48%) were for a parotid gland and 73 (52%) for a submandibular
gland. The sialendoscopy was interventional in 81 cases (58%), diagnostic in 56
(40%), and not possible to perform in 3 (2.1%). A total of 21 complications were
registered for 21 sialendoscopies (15%) and 21 patients (18%). The most common
complication was infection, in 9 cases (6.4%). Other observed complications were
salivary duct perforation (4 cases), prolonged glandular swelling (3 cases),
transient lingual nerve analgesia (2 cases), basket entrapment (2 cases), and
transient weakness in the marginal branch of the facial nerve (1 case). All
complications were related to interventional procedures or papilla dilatation.
Failure to treat occurred in 21 (15%) sialendoscopies: sialendoscopy itself was
unsuccessful in 3 cases, and an intended intervention failed in 18 cases.
Conclusion Complications in sialendoscopy are usually related to interventional
procedures. The complications are mainly minor and temporary but lead to
additional follow-up visits, further treatments, and sometimes hospitalization.
Sialendoscopic procedures are safe but not free of complications.
PMID- 29943674
TI - Future directions for monitoring and human health research for the Arctic
Monitoring and Assessment Programme.
AB - For the last two and a half decades, a network of human health experts under the
Arctic Monitoring and Assessment Program (AMAP) has produced several human health
assessment reports. These reports have provided a base of scientific knowledge
regarding environmental contaminants and their impact on human health in the
Arctic. These reports provide scientific information and policy-relevant
recommendations to Arctic governments. They also support international agreements
such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the
Minamata Convention on Mercury. Key topics discussed in this paper regarding
future human health research in the circumpolar Arctic are continued contaminant
biomonitoring, health effects research and risk communication. The objective of
this paper is to describe knowledge gaps and future priorities for these fields.
PMID- 29943675
TI - Current Thyrotropin Immunoassays Recognize Macro-Thyrotropin Leading to
Hyperthyrotropinemia in Females of Reproductive Age.
AB - BACKGROUND: Macro-thyrotropin (macro-TSH) is a high molecular weight form of TSH
that leads to hyperthyrotropinemia. This study was undertaken to examine the
prevalence and nature of macro-TSH in females of reproductive age. METHODS: Blood
samples were taken from 1794 female patients who visited the Hamada Obstetrics
and Gynecology Hospital in Tokyo, Japan, complaining of infertility. The serum of
305 patients with TSH concentrations >2.5 mIU/L was screened for macro-TSH by the
polyethylene glycol method. Samples with TSH precipitation ratios by polyethylene
glycol >70% were further analyzed using gel filtration chromatography (GFC),
protein G columns, and 125I-TSH binding experiments. RESULTS: Screening of the
305 patients revealed that 63 had serum TSH precipitation ratios >70%. GFC
revealed that immunoreactive TSH, with a molecular weight of approximately 150
kDa, eluted at higher ratios (79.6 +/- 24.4%) in 27 of the 63 patients compared
to 0.4 +/- 2.0% in the control group. Serum TSH concentrations in 24 of the 27
patients were spuriously elevated due to human anti-mouse antibodies. Macro-TSH
was found in the other three patients, and one of them had detectable anti-TSH
autoantibodies. Eight of the remaining 36 patients who did not have high
molecular-weight TSH assessed by GFC had immunoglobulin G-associated TSH. Three
commercially available TSH immunoassays (Elecsys(r), Centaur(r), and
Architect(r)) all recognized macro-TSH leading to the elevated serum TSH
concentrations. CONCLUSIONS: Macro-TSH was present in 0.17% of infertile women.
Commercial TSH immunoassays recognized macro-TSH, resulting in the diagnosis of
hyperthyrotropinemia.
PMID- 29943676
TI - Incidence and Survival of Thyroid Cancer in Children, Adolescents, and Young
Adults in Denmark: A Nationwide Study from 1980 to 2014.
AB - BACKGROUND: Thyroid cancer constitutes a major and increasing proportion of head
and neck cancers in children and adolescents. The purpose of this study was to
determine the incidence and survival of thyroid cancer in Danish patients aged 0
24 years from 1980 to 2014. METHODS: Patients aged 0-24 years registered with
primary thyroid cancer in the Danish Cancer Registry or the Danish Pathology Data
Bank during 1980-2014 were included. Crude incidence rates and age-adjusted
incidence rates (AAIR) per 100,000, average annual percent change (AAPC), and
overall survival (OS) were evaluated in relation to sex, histopathological tumor
type, age at diagnosis, and year of diagnosis. RESULTS: A total of 297 thyroid
cancer patients (72% female, 72% papillary carcinoma) were identified. The AAIR
per 100,000 increased significantly from 0.36 in 1980 to 0.97 in 2014, with an
AAPC of 2.9%. There was no significant increase in incidence among children and
adolescents (0-17 years). However, among young adults (18-24 years), a
significant increase in incidence was observed (AAPC 3.7%). The incidence of
thyroid cancer increased with age from 0.05 among infants aged 0 years to 1.73
among young adults aged 24 years. Female patients and papillary carcinoma showed
significant increase in incidence (AAPC 3.3% and 3.2%), whereas male patients and
other histopathological tumor types showed no change. The 15-year OS was 99%. The
lowest 15-year OS was observed among patients with medullary carcinomas at 96%.
There was no significant difference in OS between groups based on
histopathological tumor type, and there was no significant change in OS over
time. CONCLUSION: In this nationwide study, no change in OS was observed, but a
significant increase was seen in the incidence of thyroid cancer among young
adults (aged 18-24 years), mainly attributed to an increase among females and
patients with papillary carcinoma. No increase in incidence was seen among
children and adolescents. These findings demonstrate the excellent prognosis for
children and adolescents diagnosed with thyroid cancer.
PMID- 29943677
TI - Pain in Head and Neck Cancer Survivors: Prevalence, Predictors, and Quality-of
Life Impact.
AB - OBJECTIVES: Pain is common among patients with cancer, stemming from both
malignancy and side effects of treatment. The extent to which pain persists after
treatment has received little attention. We examined the prevalence, predictors,
and impact on quality of life (QOL) caused by pain among survivors of head and
neck cancer. STUDY DESIGN: Cohort study. SETTING: Tertiary head and neck cancer
survivorship clinic. SUBJECTS AND METHODS: We identified survivors of head and
neck cancer >=1 year after diagnosis and examined the prevalence and risk factors
for development of pain. Pain and QOL were assessed with multiple QOL
instruments. Ordinal regression modeling examined predictors of pain in
survivors. RESULTS: We identified 175 patients at a median of 6.6 years after
diagnosis. Among survivors, 45.1% reported pain, and 11.5% reported severe pain.
Among patients with current pain, 46% reported low overall QOL versus only 12% of
those without pain ( P < .001). On multivariable analysis after adjustment for
age, sex, and stage of disease, pain was associated with trimodality treatment
(odds ratio [OR], 3.55; 95% CI, 1.06-12.77). Multivariable analysis of QOL issues
revealed that pain was associated with major depression (OR, 3.91; 95% CI, 1.68
9.11), anxiety (OR, 4.22; 95% CI, 2.28-7.81), poor recreation (OR, 3.31; 95% CI,
1.70-6.48), and low overall QOL (OR, 2.20; 95% CI, 1.12-4.34). CONCLUSIONS: Years
after head and neck cancer treatment, pain remains a significant problem and is
associated with worse QOL. Future efforts should focus on preventing pain from
treatment and comprehensive management.
PMID- 29943678
TI - Regulation of inflammatory response of macrophages and induction of regulatory T
cells by using retinoic acid-loaded nanostructured lipid carrier.
AB - Immunomodulatory function of all-trans retinoic acid (ATRA) has been gathering
much attention for the therapy of autoimmune diseases. ATRA is a chemically
unstable molecule which requires proper formulation for targeted delivery. Here
we examined nanostructured lipid carrier (NLC) for the formulation of ATRA. NLC
is a representative nanoparticle formulation especially suited for oral delivery.
We established the preparation procedures of ATRA-containing NLC (NLC-RA) which
minimizes the degradation of ATRA during the preparation process. NLC-RA thus
obtained was taken up by macrophages and induced anti-inflammatory response via
suppressing NF-kappaB signaling as well as via enhancing the production of anti
inflammatory cytokines. Moreover, NLC-RA enhanced differentiation of naive T
cells to regulatory T cells in the co-culture system with dendritic cells. These
results suggest that NLC-RA is a promising alternative therapy for the autoimmune
diseases especially intestinal bowel disease.
PMID- 29943680
TI - Clinical tools for chemotherapy toxicity prediction and survival in geriatric
cancer patients.
AB - Chemotherapy is one of the main treatments for cancer and is associated in many
cancers with significant benefits in overall and disease-free survival.
Nevertheless, it is also associated with adverse effects that make its
administration difficult in patients with comorbidities or decreased general
status. Older patients belong more often to these categories because of the
physiologic effects of aging in organ functions but also because of longer
effects of chronic conditions in different organs. As a result, the decision for
administration of possibly beneficial chemotherapy to older patients becomes more
problematic given that there is a requirement to balance this benefit with a
higher probability of severe adverse effects that may even culminate to patient's
demise. Thus, the ability to predict accurately the subset of older patients that
will develop severe adverse effects with chemotherapy and, conversely, those that
will tolerate it with a more acceptable adverse effect profile, is of clinical
importance. This article will discuss progress made in devising predictive tools
for use in older patients with cancer considered for receiving chemotherapy. A
discussion of recent developments on the related but distinct subject of
prediction of mortality in geriatric cancer patients with a focus on those
receiving chemotherapy will also be included to provide a data-frame of the
status of survival prediction tools in geriatric oncology patients.
PMID- 29943679
TI - Association of Thyroid Function and Autoimmunity with Ovarian Reserve in Women
Seeking Infertility Care.
AB - BACKGROUND: While overt thyroid disease is a well known risk factor for
infertility, the potential consequences of mild thyroid dysfunction or thyroid
autoimmunity remain unknown. Experimental studies suggest a considerable role for
thyroid hormone in the physiological mechanisms of ovarian reserve, but
translation of such findings to human studies remains rare. A potential role for
thyroid function in female reproduction could be especially relevant when the
cause of infertility remains unknown, such as in women with diminished ovarian
reserve (DOR) or unexplained infertility. The aims of this study were to
investigate the association of thyroid function and autoimmunity with markers of
ovarian reserve day 3 follicle-stimulating hormone (FSH) concentrations and
antral follicle count (AFC), and to investigate whether thyroid function or
autoimmunity may have different effects in women with DOR or unexplained
infertility. METHODS: Thyrotropin, free thyroxine, thyroxine, free
triiodothyronine (fT3), triiodothyronine, thyroid peroxidase antibodies (TPOAbs),
and thyroglobulin antibodies (TgAbs), as well as AFC and the day 3 FSH
concentration, were measured among women seeking fertility treatment at the
Massachusetts General Hospital Fertility Center. Multiple linear or mixed
regression models were used to study the association of thyroid function or
autoimmunity with AFC or day 3 FSH. RESULTS: In the total study population (436
women, 530 AFC measurements), there was no association of thyroid function or
TPOAb positivity with AFC. However, TgAb positivity was associated with a higher
AFC (mean difference = 3.4 [95% confidence interval (CI) 1.8-5.1], p < 0.001). In
women with DOR or unexplained infertility, lower fT3 and TPOAb positivity were
associated with a lower AFC (fT3: continuous nonlinear association, p = 0.009;
TPOAb positivity: -2.3 follicles [confidence interval -3.8 to -0.5], p = 0.01),
while TgAb positivity was not associated with AFC. Neither thyroid function nor
thyroid antibody positivity was associated with the day 3 FSH concentration.
CONCLUSIONS: This study found that lower fT3 and TPOAb positivity are associated
with a lower AFC in women with DOR or unexplained infertility. Future studies are
required to replicate these findings and further elucidate the role of TgAbs and
underlying mechanisms through which thyroid function and autoimmunity is
associated with ovarian reserve.
PMID- 29943681
TI - The impact of alerting designs on air traffic controller's eye movement patterns
and situation awareness.
AB - : This research investigated controller' situation awareness by comparing
COOPANS's acoustic alerts with newly designed semantic alerts. The results
demonstrate that ATCOs' visual scan patterns had significant differences between
acoustic and semantic designs. ATCOs established different eye movement patterns
on fixations number, fixation duration and saccade velocity. Effective decision
support systems require human-centered design with effective stimuli to direct
ATCO's attention to critical events. It is necessary to provide ATCOs with
specific alerting information to reflect the nature of the critical situation in
order to minimise the side effects of startle and inattentional deafness.
Consequently, the design of a semantic alert can significantly reduce ATCOs'
response time, therefore providing valuable extra time in a time-limited
situation to formulate and execute resolution strategies in critical air safety
events. The findings of this research indicate that the context-specified design
of semantic alerts could improve ATCO's situational awareness and significantly
reduce response time in the event of Short Term Conflict Alert (STCA) activation
which alerts to two aircraft having less than the required lateral or vertical
separation. Practitioner Summary: Eye movements are closely linked with visual
attention and can be analysed to explore shifting attention whilst performing
monitoring tasks. This research has found that context-specific designed semantic
alerts facilitated improved ATCO cognitive processing by integrating visual and
auditory resources. Semantic designs have been demonstrated to be superior to
acoustic design by directing the operator's attention more quickly to critical
situations. ABBREVIATIONS: APW: area proximity warning; ASRS: aviation safety
reporting system; ATC: air traffic control; ATCO: air traffic controller; ATM:
air traffic management; COOPANS: cooperation between air navigation service
providers; HCI: human-computer interaction; IAA: irish aviation authority; MSAW:
minimum safe altitude warning; MTCD: medium-term conflict detection; SA:
situation awareness; STCA: short term conflict alert; TP: trajectory prediction.
PMID- 29943682
TI - Impact of non-alcoholic fatty liver disease on pregnancy.
PMID- 29943683
TI - Prognosis of Acute Subdural Hematoma in the Elderly: A Systematic Review.
AB - Acute subdural hematoma (aSDH) is among the most common injury types encountered
by neurosurgeons, and carries a poor prognosis, particularly in the elderly. As
the incidence of aSDH in the elderly population rises, identifying those patients
who may benefit from operative intervention is crucial. This systematic review
aimed to identify data on prognostic factors or indices, such as the modified
frailty index, that may help predict outcome, and hence guide management. A
comprehensive search of online databases was conducted by two independent
authors, and data on prognostic factors and outcomes were extracted. The quality
of the evidence was evaluated using the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) criteria. Of 769 studies identified in the
initial search, 7 satisfied inclusion and exclusion criteria. Mortality and
morbidity varied considerably among studies. Initial Glasgow Coma Scale (GCS) of
3-8 was the most consistently reported negative prognostic feature. Several
studies evaluated the impact of medical comorbidities and premorbid frailty, but
were limited by small sample size. A previous history of pneumonia was shown to
increase the risk of Glasgow Outcome Score (GOS) 1-3 (odds ratio [OR] 6.4 [95% CI
1.6-25.2], p = 0.04) in a single study, which also reported a greater increase in
GOS at 3 months in those with fewer than five comorbidities (56% vs. 19%, p <
0.01). There are limited data describing prognostic factors or the use of frailty
indices within the specific group of elderly patients with aSDH. Prospective
research is needed to evaluate the utility of accurate and validated assessments
of frailty to enhance the neurosurgeon's ability to appropriately manage this
complex and expanding patient group.
PMID- 29943684
TI - Overcoming the challenges of RNAi-based therapy: an interview with James
Hamilton.
AB - J Hamilton currently serves as vice president of Clinical Development at
Arrowhead Pharmaceuticals, Inc. (CA, USA), where he is responsible for clinical
strategy, clinical trial design, implementation and execution. In this role, he
managed the ARC-520, ARC-521 and ARC-AAT global programs. Previously, he was
medical director and head of Corporate Development at Arrowhead. He led
Arrowhead's acquisition of the Novartis RNAi assets and led Arrowhead's $670
million cardiovascular deal with Amgen (CA, USA). He earned an MD and MBA at The
Ohio State University (USA) and is a licensed physician with board certification
in emergency medicine. J Hamilton speaks to Hannah Makin, commissioning editor.
PMID- 29943685
TI - Industry update: the latest developments in the field of therapeutic delivery 1
28 February 2018.
PMID- 29943686
TI - Micro and nanoneedles for drug delivery and biosensing.
AB - Delivering therapeutics in a painless manner is one of the many objectives for
the treatment of clinical conditions. Micro and nanoneedles are small-scale
devices that can help overcome the resistance encountered during drug diffusion
by creating conduits of small dimensions through biomembranes. Microneedles for
drug delivery applications were manually produced until the 1990s and after this
the high precision technology from the semiconductor industry was adopted for
their production [ 1 ]. Over the last decade or so, microneedles for
transdermal applications have been widely studied. Currently, microneedle
patches, mainly based on hyaluronates, are available over the counter for
cosmetic applications. On the other hand, nanoneedles are used in atomic force
microscopy, which has been explored for drug delivery and biosensing over the
last two decades [ 2 , 3 ]. Micro and nanoneedle-based biosensing also poses
potential for environment-responsive drug delivery. In this article, the current
research, clinical studies and future perspectives of micro and nanoneedle-based
systems are discussed for drug delivery and biosensing applications.
PMID- 29943687
TI - Industry update March 2018.
AB - The present industry update covers the period 1-31 March 2018. Sources of
information included company press releases, regulatory and patent agencies
notices and various news websites. A number of companies reported positive early
stage clinical trial results for therapeutic candidates enabled by different
delivery strategies including Cerenis Therapeutics Inc. and Enteris. March also
saw the announcement of some significant collaborations; Bluebird Bio and Celgene
announced plans for a collaboration with a view to developing a novel CAR-T
therapy, and Windtree Therapeutics Inc. and Eleison Pharmaceuticals Inc. agreed
to form a partnership to facilitate the delivery of inhaled liquid cisplatin.
InMed Pharmaceuticals and OncoSec Medical Inc., companies engaged at preclinical
evaluation of their delivery technologies, also announced publications this month
on the development of their platforms.
PMID- 29943688
TI - Evidence for intranasal oxytocin delivery to the brain: recent advances and
future perspectives.
AB - The neuropeptide oxytocin plays an evolutionarily conserved role in mammalian
social behavior. Despite striking effects on animal social behavior after
intracerebroventricular drug delivery, this delivery mode is impractical in
humans. Intranasal oxytocin delivery provides a noninvasive alternative to
increase central oxytocin activity, and has shown promise as a treatment for
psychiatric illnesses. Intranasal oxytocin delivery is purported to increase
central oxytocin concentrations via channels surrounding trigeminal and olfactory
nerve fibers, which may facilitate increased activity at central oxytocin
receptors. This report outlines the evidence for intranasal oxytocin delivery
increasing central concentrations or activity, identifies current knowledge gaps
and highlights future research opportunities. Recent efforts to enhance
intranasal oxytocin delivery via improved intranasal delivery technology and dose
ranging studies are discussed.
PMID- 29943689
TI - The role of nanoparticles in the improvement of systemic anticancer drug
delivery.
AB - The systemic delivery of drugs to the body via circulation after oral
administration is a preferred method of drug administration during cancer
treatment given its ease of implementation. However, the physicochemical
properties of many current anticancer drugs limit their effectiveness when
delivered by systemic routes. The use of nanoparticles (NPs) has emerged as an
effective means of overcoming the inherent limitations of systemic drug delivery.
We provide herein an overview of various NP formulations that facilitate
improvements in the efficacy of various anticancer drugs compared with the free
drug. This review will be useful to the reader who is interested in the role NP
technology is playing in shaping the future of chemotherapeutic drug delivery and
disease treatment.
PMID- 29943690
TI - Fabrication and Characterization of Silk Microfiber-Reinforced Methacrylated
Gelatin Hydrogel with Turnable Properties.
AB - Despite considerable research effort, the natural hydrogels presently available
for tissue engineering suffer from several major drawbacks, one of the
significant issue is their poor mechanical strength which are unable to satisfy
some mechanical requirements for successful outcomes. Herein, to mimic the
composition and structure of the natural extracellular matrix, the micron-sized
silk fibers obtained by alkaline hydrolysis were used as a reinforcement phase in
a GelMA hydrogel, resulting in a material with significantly greater stiffness
than pure GelMA hydrogel alone. In addition, the hydrogel demonstrated tunable
compressive strength, swelling capacity, and degradation properties based on the
silk fiber length. Experiments with cells indicated that MC3T3-E1 pre-osteoblasts
quickly adhered to and proliferated on the surface of the composite hydrogels, as
revealed by FDA/PI staining and CCK-8 assays. In addition, various cellular
responses, including cell adhesion, changes in cellular morphology and cell
proliferation behavior, occurred on the composite hydrogel and varied with fiber
length. Overall, this study introduces a series of fiber-reinforced, tunable
composite hydrogels that could be useful for various tissue engineering
applications.
PMID- 29943691
TI - ILUVIEN(r) technology in the treatment of center-involving diabetic macular
edema: a review of the literature.
AB - Diabetic macular edema (DME) is one of the major causes of blindness, caused
primarily by hyperglycemia and results from multiple pathological processes
mostly secondary to increased levels of VEGF and other inflammatory cytokines.
DME management includes control of systemic risk factors together with laser
photocoagulation, frequent intraocular injections of anti-VEGF agents and
steroids implants. Recent adoption of novel alternative drug delivery options has
led to the development of sustained release ocular implants with longer duration
of action with less injection frequency. This article will review the
pharmacology and clinical data in terms of efficacy, safety and benefits of the
sustained release steroid implants in treatment of DME with special emphasis on
the fluocinolone acetonide ILUVIEN(r) implant.
PMID- 29943692
TI - Increases in fatigue do not change spasticity scores in persons with multiple
sclerosis.
AB - AIM: Fatigue is a common finding in multiple sclerosis (MS) which may result in
worsening of gait, function and other MS symptoms, like spasticity. Although the
worsening of spasticity with fatigue has been reported by persons with MS, the
effect of fatigue on spasticity has not been measured. PURPOSE: The purpose of
this study was to compare lower extremity Modified Ashworth Scale (MAS) scores of
persons with mild-to-moderate MS symptoms before and after fatigued and
unfatigued conditions. METHODS: Using a randomized crossover design, MS subjects
underwent 6-min walk to induce fatigue and 6-min supine rests, with lower
extremity spasticity measured before and after each condition. Friedman tests
gave paired comparisons of MAS before and after each condition. RESULTS: 16
subjects with mild-to-moderate MS completed the study (mean age = 56; standard
deviation = 11.7). Friedman tests showed a significant decrease in mean rank for
overall average MAS for both lower extremities (p = 0.031) when comparing
fatigued to unfatigued conditions. This appeared to be driven by the right lower
extremity average MAS (p = 0.002) and, more specifically, in post hoc pre to post
test comparisons for right knee flexor (p = 0.002 fatigued; p = 0.059 unfatigued)
and right knee extensor (p = 0.001 fatigued; p = 0.020 unfatigued) MAS mean rank
differences. Fatigue did not result in increased spasticity. CONCLUSION:
Spasticity in these subjects with MS was not worsened by fatigue suggesting that
worsening of gait with fatigue may be due to causes other than spasticity.
PMID- 29943693
TI - Phase III SUNBEAM and RADIANCE PART B trials for Ozanimod in relapsing multiple
sclerosis demonstrate superiority versus interferon-beta-1a (Avonex(r)) in
reducing annualized relapse rates and MRI brain lesions.
AB - Biography: Volker Koscielny, MD, is the Vice President, Global Medical Affairs,
for Inflammation and Immunology at Celgene. Volker trained as a doctor in his
native Germany and worked for several pharmaceutical companies prior to joining
Celgene in January 2015.
PMID- 29943694
TI - Myasthenia gravis: the unmet needs of a paradigmatic autoimmune disease.
PMID- 29943695
TI - Reflections of the use of locating technologies with persons with dementia:
proceedings of a key stakeholder forum.
AB - AIM: To describe the proceedings and outcomes of a Locating Technology and
Dementia Forum that brought together 109 representatives of researchers, product
manufacturers, policy makers, Alzheimer Societies, clinicians, first responders,
persons with dementia and care partners. METHODS: Information gathered from this
event was used to create strategic direction for advancing the development and
use of locating technologies among persons with dementia. RESULTS: Key
recommendations from this forum include the need to: fund and conduct research
pertaining to usability and effectiveness of technologies; increase awareness
about the risk of missing person events; develop a guideline of strategies to
manage critical wandering; and engage users in technology development and
evaluation. CONCLUSION: Results are being used to guide research and to inform
policies directed at the management of dementia-related wandering.
PMID- 29943696
TI - Corporal punishment of children: discipline or abuse?
AB - INTRODUCTION: Corporal punishment is a public health problem due to its impact on
the physical, psychological, and social interactions of children. OBJECTIVES: To
determine the knowledge of pediatricians in Lebanon regarding corporal
punishment, their preventive, educational, and legal role. METHODS: A cross
sectional descriptive study conducted on 153 pediatricians in Lebanon, by a
questionnaire distributed at the 12th Annual Congress of the Lebanese Pediatric
Society and the North Lebanon Pediatric Society. RESULTS: Less than 50% and less
then 60% of pediatricians know the effects of physical punishment on the physical
and psychic health of the child, respectively. About 74.2% and 23.2% of
pediatricians disagree with Article186 of the Lebanese Criminal Code and Lebanese
Law422/02 (Article25), respectively. Only 76.2% of Lebanese pediatricians always
advise the abandonment of corporal punishment and 4.7% advise its use for
discipline. CONCLUSION: Pediatricians play a fundamental role in the abolition of
corporal punishment, but this cannot be accomplished without improving their
skills in this area. They are invited to seek legal reforms in Lebanon to abolish
the use of corporal punishment as a means of disciplining children.
PMID- 29943697
TI - An Untapped Resource in the Spotlight of Medicinal Biotechnology: The Genus
Scutellaria.
AB - BACKGROUND: This review is intended to draw the attention of pharmaceutical and
biotechnological communities to the untapped potential of the Scutellaria genus.
Skullcaps, as they are more widely known, are found in one of the oldest materia
medica in the world, that of ancient Chinese pharmacology, and their numerous
wide range of medicinal bioactivities have been studied both in vivo and in
vitro. For thousands of years, chemical compounds from the Scutellaria species
have been safely used as antitumor, antibacterial, antiviral, anti-inflammatory,
antioxidant or hepatoprotective factors. OBJECTIVE: As these effects are well
known, reflected in the presence of Scutellaria plants in national
pharmacopoeias, it is clear that the plant has yet enormous unexploited
potential. The European pharmacological market has turned to the resources of
Scutellaria only in the last two decades, and although the construction and
clinical processing of a new drug is a long process, the general impression is
that very few medical products in pharmacies have been inspired by the
phytochemistry of skullcaps. CONCLUSION: This paper presents the current state of
knowledge on the wealth of Scutellaria chemical compounds with treatment
applications, its tissue culture and biotechnological achievements, especially in
the context of the production of secondary metabolites.
PMID- 29943698
TI - Cytotoxicity, Genotoxicity, Antioxidant Potential and Chemical Composition of
Leaves of Campomanesia pubescens (Mart. ex DC.) O.Berg.
AB - BACKGROUND: Plants of the genus Campomanesia belong to the family Myrtaceae and
are very abundant in Cerrado areas. Teas from leaves of species of this genus are
used for intestinal infections, combating obesity, stomach pathology, fever and
among others. OBJECTIVE: The present study evaluated the chemical composition and
antioxidant potential, cytotoxicity and genotoxicity of ethanolic extract from
leaves of Campomanesia pubescens (Mart. ex DC.) O.Berg. METHOD: For the
evaluation of antioxidant activity, the free radical DPPH and for determination
of phenolic compounds Folin-Ciocalteau reagent were used. Identification of the
substances was performed by HPLC-DAD by comparison of the retention times with
standards analyzed under the same conditions and by evaluation of molecular
absorption spectra in the ultraviolet and visible region. The cytotoxicity,
genotoxicity were evaluated using Allium cepa bioassay. RESULTS: In the ethanolic
extract 7-hydroxy-6-methyl-5-methoxyflavanone, 5,7-dihydroxy-6-methylflavanone,
5,7-dihydroxy-8-methylflavanone, 2',4'-dihydroxy-6'-methoxychalcone, 5,7
dihydroxy-6,8- dimethylflavanone, 2',4'-dihydroxy-5'-methyl-6'-methoxychalcone
and 2',4'-dihydroxy-3',5'-dimethyl-6'- methoxychalcone were identified. The
extract showed antioxidant activity and cytotoxic effects on cell division and
increased chromosomal alterations in Allium cepa test. CONCLUSION: These results
showed antioxidant activity and suggest the cytotoxic and genotoxic effects in
Allium cepa of ethanolic extract obtained from the leaves of Campomanesia
pubescens.
PMID- 29943699
TI - Differential Approaches are Much Needed for "Real World" Management of
Hypertension in the Era of "Hypertension Paradox".
PMID- 29943700
TI - Autophagy: a promising target for age-related osteoporosis.
AB - Autophagy is a process the primary role of which is to clear up damaged cellular
components such as long-lived proteins and organelles, thus participating in the
conservation of different cells. Osteoporosis associated with aging is
characterized by consistent changes in bone metabolism with suppression of bone
formation as well as increased bone resorption. In advanced age, not only bone
mass but also bone strength decrease in both sexes, resulting in an increased
incidence of fractures. Clinical and animal experiments reveal that age-related
bone loss is associated with many factors such as accumulation of autophagy,
increased levels of reactive oxygen species, sex hormone deficiency, and high
levels of endogenous glucocorticoids. Available basic and clinical studies
indicate that age-associated factors can regulate autophagy. Those factors play
important roles in bone remodeling and contribute to decreased bone mass and bone
strength with aging. In this review, we summarize the mechanisms involved in bone
metabolism related to aging and autophagy, supplying a theory for therapeutic
targets to rescue bone mass and bone strength in older people.
PMID- 29943701
TI - Asymmetric Finite Size of Ions and Orientational Ordering of Water in Electric
Double Layer Theory Within Lattice Model.
AB - In the present review, a brief historical survey of the mean-field theoretical
description of Electric Double Layer (EDL) is presented. Special attention is
devoted to asymmetric finite size of ions and orientational ordering of water
dipoles. A model of Wicke and Eigen, who were first to explicitly derive the ion
distribution functions for finite size of ions, is discussed. Arguments are given
in favour of changing the recently adopted name of the mean-field EDL model for
finite size of ions from Bikerman model to Bikerman-Wicke-Eigen model.
Theoretically predicted asymmetric and symmetric camel-like shape of the voltage
dependence of the differential capacitance is also discussed.
PMID- 29943702
TI - Prognostic Value of White Blood Cell in Acute Ischemic Stroke Patients.
AB - BACKGROUND AND AIMS: It is unclear whether white blood cell on admission has a
prognosis value on ischemic stroke and whether its function is affected by other
inflammation factors. We hypothesized that elevated white blood cell is
associated with stroke severity and 3-month mortality after acute ischemic
stroke. METHODS: A total of 3891 acute ischemic stroke subjects from the China
Antihypertensive Trial in Acute Ischemic Stroke (CATIS) were included in this
analysis. Participants were divided into four groups according to quartiles of
white blood cell on admission (cutoff points for the quintiles:
5.60*109/L,6.83*109/L,8.50*109/L). The primary outcome was a combination of death
and major disability (modified Rankin Scale score >=3) at 3 months. Secondary
outcomes were major disability, death, and vascular events, respectively.
RESULTS: After adjustment for major conventional risk factors, elevated white
blood cell on admission was associated with poor primary and secondary outcomes
after acute ischemic stroke. Compared with the lowest quartile, the ORs (95% CIs)
for the highest quartile were 1.79 (1.37-2.91) and 1.62 (1.21-3.55) for primary
outcome in model 1 and model 2. In addition, there was a linear association
between white blood cell and primary outcome at 3-months (P for linear trend =
0.001). CONCLUSION: This analysis indicated that elevated white blood cell on
admission is associated with 3-months poor prognosis in ischemic stroke patients
independently of other inflammation factors. The results emphasize the need for
further research on the application of anti-inflammatory therapy.
PMID- 29943703
TI - Synthesis, Characterization, Antimicrobial and Antioxidant Potential of Diazenyl
Chalcones.
AB - A series of diazenyl chalcones was prepared by base catalyzed Claisen-Schmidt
condensation of synthesized hydroxy substituted acetophenone azo dye with various
substituted aromatic/ heteroaromatic aldehydes. The structural conformation of
synthesized chalcones was done by a number of physicochemical and spectral means
like FTIR, UV-visible, mass, NMR spectroscopy and CHNS/O analysis. These diazenyl
chalcones were assessed for their in vitro antimicrobial potential against
several Gram-negative, Gram-positive bacterial and fungal strains by serial tube
dilution method. The fluconazole and cefadroxil were used as standard drugs. The
target compounds were also evaluated for their antioxidant potential by DPPH
assay. (2E)-3-(2,4-Dichlorophenyl)-1-(4-((2,6-
dihydroxyphenyl)diazenyl)phenyl)prop-2-en-1-one (C-7) had shown very good
antimicrobial potential with MIC ranges from 3.79 to 15.76 MUg/ml against most of
the tested microorganisms. Most of the synthesized diazenyl chalcones were found
to be active against B. subtilis. The (2E)-1-(5-((2-Chloro- 4
nitrophenyl)diazenyl)-2-hydroxyphenyl)-3-(2-hydroxynaphthalen-1-yl)prop-2-en-1
one (C-10) had shown high free radical-scavenging activity when compared with the
ascorbic acid as the reference antioxidant.
PMID- 29943704
TI - PCR Amplification Strategies Towards Full-length HIV-1 Genome Sequencing.
AB - The advent of next-generation sequencing has enabled greater resolution of viral
diversity and improved feasibility of full viral genome sequencing allowing
routine HIV-1 full genome sequencing in both research and diagnostic settings.
Regardless of the sequencing platform selected, successful PCR amplification of
the HIV-1 genome is essential for sequencing template preparation. As such, full
HIV-1 genome amplification is a crucial step in dictating the successful and
reliable sequencing downstream. Here we reviewed existing PCR protocols leading
to HIV-1 full genome sequencing. In addition to the discussion on basic
considerations on relevant PCR design, the advantages as well as the pitfalls of
the published protocols were reviewed.
PMID- 29943705
TI - Mosquito and Tick-borne Illnesses in the United States. Guidelines for the
Recognition and empiric Treatment of Zoonotic Diseases in the Wilderness.
AB - In the United States, tick-borne illnesses account for a significant number of
patients that have been seen and treated by health care facilities. This in turn,
has resulted in a significant morbidity and mortality and economic costs to the
country. The distribution of these illnesses is geographically variable and is
related to the climate as well. Many of these illnesses can be diagnosed and
treated successfully, if recognized and started on appropriate antimicrobial
therapy early in the disease process. Patient with illnesses such as Lyme
disease, Wet Nile illness can result in chronic debilitating diseases if not
recognized early and treated. This paper covers illnesses such as Lyme disease,
West Nile illness, Rocky Mountain Spotted fever, Ehrlichia, Tularemia, typhus,
mosquito borne illnesses such as enteroviruses, arboviruses as well as arthropod
and rodent borne virus infections as well. It covers the epidemiology, clinical
features and diagnostic tools needed to make the diagnosis and treat these
patients as well.
PMID- 29943706
TI - MicroRNA-223 Regulates Septin-2 and Septin-6 in Stored Platelets.
AB - BACKGROUND: Septins have been identified to play important roles in platelets,
but their regulation in platelets is unknown. Human platelet being an enucleated
and terminally differentiated cell, mRNA downregulation by miRs is one of the
posttranscriptional mechanisms operative in platelets. OBJECTIVE: Since platelets
are known to have miR-223 in abundance, the objective of this study is to test
whether a) platelet septins have miR-223 interacting target sites in their mRNA
3'UTRs, b) septin mRNAs and miR-223 form complexes with Argonaute 2 (AGO2)
protein in platelets, which is the catalytic component of an RNA Induced
Silencing Complex (RISC), c) a reporter gene with septin mRNA 3' untranslated
region (UTR) is subjected to downregulation by miR-223 and d) anti-miR-223 can
suppress miR-223 activity and enhance septin-2 expression in platelets. METHOD:
Bioinformatics tools were used to screen mRNA 3'UTRs of septin-2 and septin-6 for
miR- 223 target sites. Subsequently, platelet extracts were immunoprecipitated by
AGO2 antibodies to identify that the two septin mRNAs and miR-223 were in complex
with AGO2. A luciferase reporter chimeric- gene expression system was utilized to
monitor miR-223 mediated downregulation luciferase gene containing the 3'UTR of
either septin-2 or septin-6. Further, anti-miR-223 was utilized in platelets to
directly demonstrate the role of miR-223 on the expression of septin-2. RESULTS:
Our results demonstrate that in stored platelets a) septine-2 and septin-6 mRNAs
have miR- 223 target sites, b) septin-2 and septin-6 are in complex with Ago-2,
c) in luciferase reporter gene system, the interaction of miR-223 with 3' UTRs of
septin-2 and septin-6 leads to downregulation of luciferase expression and d)
anti-miR-223 downregulated miR-223 activity and thereby the expression of septin
2 is upregulated. CONCLUSION: The results demonstrate that like in nucleated
cells, enucleated platelets also have miRbased mechanisms for the regulation of
their septins.
PMID- 29943707
TI - Molecular Characterization of Tandem Repeat Protein 36 Gene of Ehrlichia canis
Detected in Naturally Infected Dogs from Peru.
AB - Ehrlichia spp. are emerging infectious pathogens, especially in the Americas.
Although Ehrlichia canis is primarily a parasite of dogs, polymerase chain
reaction-confirmed human infections have been reported from Mexico, Venezuela,
and Costa Rica. This study reports the presence of E. canis DNA in 13.7% of 205
dogs from urban areas in Peru and of those, five were analyzed for phylogenetic
variation using the Tandem Repeat Protein 36 (TRP36) gene. The use of the TRP36
gene for such analysis was validated against 16S rRNA and heat shock protein
genes using Shannon's entropy bioinformatic approach. When compared with other E.
canis strains previously reported, three unique and novel E. canis strains were
detected. In addition, the TRP36 amino acid tandem repeat sequences of the
Peruvian strains share close similarity to an E. canis strain detected from four
human blood bank samples in Costa Rica. This study reports for the first time
domestic dogs infected with E. canis strains closely related to a zoonotic
strain, which may be of public health concern as dogs can be chronically infected
with this pathogen.
PMID- 29943708
TI - Experimental Infection of Rattus norvegicus by the Group II Intermediate
Pathogen, Leptospira licerasiae.
AB - Leptospira licerasiae serovar Varillal, a group II intermediate pathogen
species/serovar discovered in the Peruvian Amazon city of Iquitos, is commonly
recognized in this region by sera from humans (at least 40% seroprevalence)
without a known clinical history of leptospirosis. This high frequency of human
seroreactivity remains unexplained. To test the hypothesis that the oral route of
infection might explain the high rate of human seroreactivity against L.
licerasiae, an experimental infection model using Rattus norvegicus was
developed, given that rats were one of the original reservoir hosts identified as
being colonized by this leptospire. Sprague-Dawley rats were experimentally
exposed via mucosa, direct gastric gavage, or parenteral inoculation with nine
different isolates of L. licerasiae originally isolated from Peruvian humans,
peridomiciliary rodents, and wildlife. As shown by quantitative polymerase chain
reaction of kidney tissue, Leptospira infection via these routes of infection was
equally successful. Importantly, the data show that L. licerasiae infects R.
norvegicus via the oral route, leading to renal colonization. Not only do these
findings confirm the infectiousness of group II Leptospira, but also they
underscore the potential importance of oral as well as mucosal and transcutaneous
routes of Leptospira infection.
PMID- 29943709
TI - Evaluation of Treatment Coverage and Enhanced Mass Drug Administration for
Onchocerciasis and Lymphatic Filariasis in Five Local Government Areas Treating
Twice Per Year in Edo State, Nigeria.
AB - The western region of Edo state in southern Nigeria is highly endemic for
onchocerciasis. Despite years of mass drug administration (MDA) with ivermectin
(IVM), reports suggest persistently high prevalence of onchocerciasis, presumably
because of poor coverage. In 2016, twice-per-year treatment with IVM (combined
with albendazole for lymphatic filariasis in the first round where needed) began
in five local government areas (LGAs) of Edo state. We undertook a multistage
cluster survey within 3 months after each round of MDA to assess coverage. First
round coverage was poor: among 4,942 people of all ages interviewed from 145
clusters, coverage was 31.1% (95% confidence intervals [CI]: 24.1-38.0%). Most
respondents were not offered medicines. To improve coverage in the second round,
three LGAs were randomized to receive MDA through a "modified campaign" approach
focused on improved supervision and monitoring. The other two LGAs continued with
standard MDA as before. A similar survey was conducted after the second round,
interviewing 3,362 people in 87 clusters across the five LGAs. Coverage was not
statistically different from the first round (40.0% [95% CI: 31.0-49.0%]) and
there was no significant difference between the groups (P = 0.7), although the
standard MDA group showed improvement over round 1 (P < 0.01). The additional
cost per treatment in the modified MDA was 1.6 times that of standard MDA.
Compliance was excellent among those offered treatment. We concluded that poor
mobilization, medicine distribution, and program penetration led to low coverage.
These must be addressed to improve treatment coverage in Edo state.
PMID- 29943711
TI - Activity of Ceftolozane-Tazobactam against Burkholderia pseudomallei.
AB - We investigated the in vitro activity of a novel fifth-generation cephalosporin
tazobactam combination, ceftolozane-tazobactam against Burkholderia pseudomallei,
the etiological agent of melioidosis. Using both disc diffusion and minimum
inhibitory concentration (MIC) strip techniques against 56 clinical isolates and
an national collection of type cultures (NCTC) strain, the MIC to ceftolozane
tazobactam was found to be between 0.75 and 4 mcg/mL. The MIC50 was found to be
1.5 mcg/mL and MIC90 was 2.0 mcg/mL. This study provides initial evidence of
ceftolozane-tazobactam as a novel agent in the management of melioidosis.
PMID- 29943710
TI - An Improved Enzyme-Linked Immunoassay for the Detection of Leptospira-Specific
Antibodies.
AB - Leptospirosis is a neglected zoonotic disease with worldwide endemicity and
continues to be a significant public health burden on resource-limited
populations. Previously, we produced three highly purified recombinant antigens
(rLipL32, rLipL41, and rLigA-Rep) and evaluated their performance of detecting
Leptospira-specific antibodies in enzyme-linked immunosorbent assay (ELISA) as
compared with the microscopic agglutination test (MAT). The overall sensitivity
of this assay approached 90%. Recently, another recombinant antigen (rLigB-Rep)
was prepared. We tested each individual antigen and a 1:1:1:1 mixture of these
four antigens for the detection of Leptospira-specific antibodies in ELISA. The
performance of these recombinant antigens was evaluated with a much larger
febrile patient panel (337 MAT-confirmed positive sera and 92 MAT-negative sera
from febrile patients). Combining the detection results of immunoglobulin M and
immunoglobulin G from these four individual antigens, the overall sensitivity was
close to 90% but the specificity was only 66%, based on the MAT reference method.
The overall sensitivity and specificity of the four-antigen mixture were 82% and
86%, respectively. The mixture of four antigens also exhibited a broader
reactivity with MAT-positive samples of 18 serovars from six major pathogenic
Leptospira species. Given the limitations of MAT, the data were further analyzed
by Bayesian latent class model, showing that ELISA using a 1:1:1:1 mixture still
maintained high sensitivity (79%) and specificity (88%) as compared with the
sensitivity (90%) and specificity (83%) of MAT. Therefore, ELISA using a mixture
of these four antigens could be a very useful test for seroprevalence studies.
PMID- 29943712
TI - Human Strongyloidiasis in Hawaii: A Retrospective Review of Enzyme-Linked
Immunosorbent Assay Serodiagnostic Testing.
AB - Human strongyloidiasis is widely prevalent in tropical and subtropical regions
worldwide but is not endemic in Hawaii. Subclinical, chronic infections may be
lifelong; immunosuppressive therapy, particularly with glucocorticoids, may lead
to serious or fatal disseminated disease, which is preventable. We performed a
retrospective analysis of patients tested for Strongyloides immunoglobulin G
antibody in an academic medical center in Honolulu, Hawaii, from 2005 to 2012. Of
the 475 patients tested, 78 (16%) were seropositive. The largest proportion of
seropositive cases was found among Micronesians (30%), Polynesians (26%),
Filipinos (13%), and Southeast Asians (11%). Among the seropositive patients, the
most likely reason for clinicians to order testing was blood eosinophilia. Stool
parasite examination results were available for 58% of seropositive patients of
which 11% were positive for Strongyloides stercoralis larvae. Antihelminthic
therapy, usually ivermectin, was ordered for 71% of patients. After treatment,
blood eosinophilia and Strongyloides serology results were reassessed for 76% and
35% of patients, respectively; both tests tended to show improvement. Travelers
and immigrants from Strongyloides-endemic areas, including Micronesia and
Polynesia, should have serodiagnostic testing for latent strongyloidiasis, and if
positive, treated empirically with ivermectin, particularly when corticosteroids
or other immunosuppressive therapies are anticipated.
PMID- 29943713
TI - Serotype Distribution and Antimicrobial Resistance of Shigella Species in Bangui,
Central African Republic, from 2002 to 2013.
AB - Shigella is a major cause of severe diarrhea in children less than the age of 5
years in sub-Saharan Africa. The aim of this study was to describe the (sub
)serotype distribution and antimicrobial susceptibility of Shigella serogroups
from Centrafrican patients with diarrhea between 2002 and 2013. We collected 443
Shigella isolates in total. The most common serogroups were Shigella flexneri (N
= 243, 54.9%), followed by Shigella sonnei (N = 90, 20.3%) and Shigella
dysenteriae (N = 72, 16.3%). The high diversity of (sub-)serotypes of S. flexneri
and S. dysenteriae may impede the development of an efficient vaccine. Rates of
resistance were high for ampicillin, chloramphenicol, tetracycline, and
cotrimoxazole but low for many other antimicrobials, confirming recommendations
for the use of third-generation cephalosporins (only one organism resistant) and
fluoroquinolones (no resistance). However, the detection of one extended-spectrum
beta-lactamase-producing Shigella organism highlights the need for continued
monitoring of antimicrobial drug susceptibility.
PMID- 29943714
TI - Q Fever in Military Firefighters during Cadet Training in Brazil.
AB - We report five cases of Q fever among cadets during a training program for
Military Firefighters Academy in the state of Rio de Janeiro, Brazil. This
cluster confirms the significance of Coxiella burnetii as an infectious agent in
Brazil, where the occurrence of this zoonosis is poorly documented and highlights
the potential risk for Q fever transmission in rural areas or farms with infected
animals.
PMID- 29943715
TI - Mixed Infection with Severe Fever with Thrombocytopenia Syndrome Virus and Two
Genotypes of Scrub Typhus in a Patient, South Korea, 2017.
AB - Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease
with a high mortality rate. Infection can also occur through close contact with
an infected patient. Scrub typhus is an acute febrile illness caused by Orientia
tsutsugamushi, a bacterium transmitted to humans through chigger mite bites.
South Korea is an endemic region of SFTS and scrub typhus. In this study, we
confirmed that a patient was coinfected with SFTS virus and two (Boryong and
Taguchi) genotypes of O. tsutsugamushi.
PMID- 29943717
TI - How Far Are We from Reaching Universal Malaria Testing of All Fever Cases?
AB - Universal malaria diagnostic testing of all fever cases is the first step in
correct malaria case management. However, monitoring adherence to universal
testing is complicated by unreliable recording and reporting of the true number
of fever cases. We searched the literature to obtain gold-standard estimates for
the proportion of patients attending outpatient clinics in sub-Saharan Africa
with malarial and non-malarial febrile illness. To correct for differences in
malaria transmission, we calculated the proportion of patients with fever after
excluding confirmed malaria cases. Next, we analyzed routine data from Guinea and
Senegal to calculate the proportion of outpatients tested after exclusion of
confirmed malaria cases from the numerator and denominator. From 12 health
facility surveys in sub-Saharan Africa with gold-standard fever screening, the
median proportion of febrile illness among outpatients after exclusion of
confirmed malaria fevers was 57% (range: 46-80%). Analysis of routine data after
exclusion of confirmed malaria cases demonstrated much lower testing proportions
of 23% (Guinea) and 13% (Senegal). There was substantial spatial and temporal
heterogeneity in this testing proportion, and testing in Senegal was correlated
with malaria season. Given the evidence from gold-standard surveys that at least
50% of non-malaria consultations in sub-Saharan Africa are for febrile illness,
it appears that a substantial proportion of patients with fever are not tested
for malaria in health facilities when considering routine data. Tracking the
proportion of patients tested for malaria after exclusion of the confirmed
malaria cases could allow programs to make inferences about malaria testing
practices using routine data.
PMID- 29943716
TI - Case Report: Fulminant Murine Typhus Presenting with Status Epilepticus and Multi
Organ Failure: an Autopsy Case and a Review of the Neurologic Presentations of
Murine Typhus.
AB - Murine typhus (MT) is an important cause of febrile illness in endemic areas, and
there is an epidemiologic resurgence of this infection currently transpiring in
Texas and California. Fatal cases and severe neurological complications are rare.
A fatal case of MT in a middle-aged man is reported with a course culminating in
multi-organ failure and refractory status epilepticus. An autopsy revealed
hemorrhagic pneumonia, acute tubular necrosis, and ischemic necrosis in the
liver, adrenals, and brain. We have also reviewed the neurologic complications of
MT.
PMID- 29943718
TI - Protobothrops mucrosquamatus Bites to the Head: Clinical Spectrum from Case
Series.
AB - Protobothrops mucrosquamatus (Trimeresurus mucrosquamatus) is a medically
important species of pit viper with a wide geographic distribution in Southeast
Asia. Bites by P. mucrosquamatus mostly involve the extremities. Little is known
about the toxic effects of P. mucrosquamatus envenoming to the head because of
the infrequency of such occurrence. To better delineate the clinical
manifestations of envenoming to the head, we report three patients who suffered
from P. mucrosquamatus bites to the head and were treated successfully. All three
patients developed progressive soft tissue swelling extending from head to neck,
with two patients expanding further onto the anterior chest wall. Mild
thrombocytopenia was noted in two patients. One patient had transient acute renal
impairment and airway obstruction, necessitating emergent intubation. All three
patients received high doses of species-specific antivenom with recovery within 1
week. No adverse reactions to antivenom were observed.
PMID- 29943720
TI - Development of Loop-Mediated Isothermal Amplification-Based Lateral Flow Device
Method for the Detection of Malaria.
AB - The present study aims to develop a method for rapid diagnosis of malaria using
loop-mediated isothermal amplification (LAMP) combined with a lateral flow device
(LFD). By adding the biotin-labeled and fluorescein amidite-labeled loop primers
to the LAMP reaction solution, the end product can be visualized on a LFD. The
entire procedure takes approximately 42 minutes to complete, LAMP assay exhibited
high sensitivity, as the detection limit was 0.01 pg/MUL for all five Plasmodium
species. It was demonstrated that all Plasmodium knowlesi (N = 90) and Plasmodium
vivax (N = 56) were positively amplified by LAMP-LFD assay, whereas healthy donor
samples (N = 8) were negative. However, not all mixed infections were positive,
and other infected nonmalaria samples were negative. Loop-mediated isothermal
amplification-LFD represents a robust approach with potential suitability for use
in resource-constrained laboratories. We believe that LAMP-LFD has a potential to
be developed as point-of-care diagnostic tool in future.
PMID- 29943719
TI - Safety, Immunogenicity, and Protective Efficacy against Controlled Human Malaria
Infection of Plasmodium falciparum Sporozoite Vaccine in Tanzanian Adults.
AB - We are using controlled human malaria infection (CHMI) by direct venous
inoculation (DVI) of cryopreserved, infectious Plasmodium falciparum (Pf)
sporozoites (SPZ) (PfSPZ Challenge) to try to reduce time and costs of developing
PfSPZ Vaccine to prevent malaria in Africa. Immunization with five doses at 0, 4,
8, 12, and 20 weeks of 2.7 * 105 PfSPZ of PfSPZ Vaccine gave 65% vaccine efficacy
(VE) at 24 weeks against mosquito bite CHMI in U.S. adults and 52% (time to
event) or 29% (proportional) VE over 24 weeks against naturally transmitted Pf in
Malian adults. We assessed the identical regimen in Tanzanians for VE against
PfSPZ Challenge. Twenty- to thirty-year-old men were randomized to receive five
doses normal saline or PfSPZ Vaccine in a double-blind trial. Vaccine efficacy
was assessed 3 and 24 weeks later. Adverse events were similar in vaccinees and
controls. Antibody responses to Pf circumsporozoite protein were significantly
lower than in malaria-naive Americans, but significantly higher than in Malians.
All 18 controls developed Pf parasitemia after CHMI. Four of 20 (20%) vaccinees
remained uninfected after 3 week CHMI (P = 0.015 by time to event, P = 0.543 by
proportional analysis) and all four (100%) were uninfected after repeat 24 week
CHMI (P = 0.005 by proportional, P = 0.004 by time to event analysis). Plasmodium
falciparum SPZ Vaccine was safe, well tolerated, and induced durable VE in four
subjects. Controlled human malaria infection by DVI of PfSPZ Challenge appeared
more stringent over 24 weeks than mosquito bite CHMI in United States or natural
exposure in Malian adults, thereby providing a rigorous test of VE in Africa.
PMID- 29943721
TI - Calcified Neurocysticercosis and Headache in an Endemic Village: A Case-Control
Study Nested to a Population-Based Cohort.
AB - Headache in patients with calcified neurocysticercosis (NCC) is probably common
but has been largely overlooked. We aimed to assess the presence,
characteristics, and diagnosis of headache across patients with calcified NCC and
their matched controls. In this case-control study nested to a population-based
cohort, Atahualpa residents aged >= 20 years with calcified NCC were identified
as case patients and paired 1:1 to age- and gender-matched randomly selected
controls. A culturally adapted questionnaire was derived from the EUROLIGHT.
Headache diagnosis was established according to the International Classification
of Headache Disorders, 3rd edition. Conditional logistic regression models for
matched paired data were fitted to assess the independent association between
calcified NCC (as the exposure) and headache variables, after adjusting for
education, alcohol intake, depression, and epilepsy. The selection process
generated 106 case patients and their matched controls. Lifetime headache
prevalence (odds ratio [OR]: 4.18; 95% Confidence Interval [CI]: 1.79-9.75; P =
0.001), current headaches (OR: 4.19; 95% CI: 1.92-9.16; P < 0.001), and intense
headaches (OR: 9.47; 95% CI: 2.88-31.19; P < 0.001) were more frequent among
cases than in controls. In addition, migraine (but not other forms of headache)
was more frequent among subjects with calcified NCC (OR: 4.89; 95% CI: 2.36
11.39; P < 0.001). This study shows a robust epidemiological association between
headache-particularly migraine-and calcified NCC.
PMID- 29943722
TI - Iron Deficiency is Prevalent among HIV-Infected Kenyan Adults and is Better
Measured by Soluble Transferrin Receptor than Ferritin.
AB - Iron deficiency (ID) and human immunodeficiency virus (HIV) infection frequently
coexist. Little data exist on ID in HIV-infected individuals, partly because the
iron marker ferritin is altered by inflammation common in HIV infection. We
measured iron biomarkers (ferritin, soluble transferrin receptor [sTfR],
hepcidin) and red cell indices (hemoglobin, mean corpuscular volume [MCV]) in
newly diagnosed, antiretroviral therapy-naive, HIV-infected (N = 138) and
uninfected (N = 52) Kenyan adults enrolled in a study of the immune response to
malaria. We compared markers between infected and uninfected groups with t test
and Wilcoxon Rank-Sum, used Spearman correlation to determine the association
between iron and inflammatory markers, and applied logistic regression to
determine which markers best predicted anemia. HIV-infected individuals had lower
hemoglobin (P < 0.001), lower MCV (P < 0.001), higher sTfR (P = 0.003), and a
greater prevalence of ID (sTfR > 8.3 mg/L) than uninfected individuals. Ferritin
was elevated in HIV-infected individuals and was more strongly correlated with C
reactive protein (rho = 0.43, P < 0.001) and hepcidin (rho = 0.69, P < 0.001)
than with hemoglobin. The best predictor of anemia in HIV-infected participants
was sTfR, with a one log-unit increase in sTfR associated with a 6-fold increase
in the odds of anemia (odds ratio = 6.3, 95% confidence interval: 1.8-21.8).
These data suggest a significant burden of ID among treatment-naive HIV-infected
Kenyan adults. Soluble transferrin receptor may be a reliable marker of ID in HIV
mediated inflammation.
PMID- 29943723
TI - Zika Virus and the World Health Organization Criteria for Determining Recent
Infection Using Plaque Reduction Neutralization Testing.
AB - The recent Zika virus (ZIKV) epidemic swept across Latin America and the
Caribbean, where dengue virus (DENV) is endemic. The antigenic similarities of
these closely related flaviviruses left researchers and clinicians with
challenges to interpret serological tests. Thirty-six women attending a prenatal
clinic in Honduras and with positive DENV IgM enzyme-linked immunoabsorbent
assays (ELISAs) were screened with a ZIKV immunoglobulin M ELISA, reverse
transcription polymerase chain reaction for ZIKV and DENV 1-4, and plaque
reduction neutralization tests (PRNTs) for ZIKV and DENV-2. Plaque reduction
neutralization test results were interpreted using the World Health Organization
(WHO) and Centers for Disease Control and Prevention (CDC) criteria. Using the
WHO criteria of a PRNT90 titer >= 20 and a 4-fold difference between ZIKV and
DENV titers, we determined that 69.4% of samples had a recent ZIKV infection,
compared with 5.6% using CDC criteria. The interpretation of ZIKV PRNTs in a DENV
endemic region is highly dependent on the choice of interpretation criteria.
PMID- 29943724
TI - Water, Sanitation, and Hygiene Services in Public Health-Care Facilities in
Indonesia: Adoption of World Health Organization/United Nations Children's Fund
Service Ladders to National Data Sets for a Sustainable Development Goal Baseline
Assessment.
AB - Provision of basic water, sanitation, and hygiene (WASH) services in health-care
facilities is gaining increased attention, given growing acceptance of its
importance to the maternal and newborn quality of care agenda and the universal
health coverage framework. Adopting and contextualizing an emerging World Health
Organization/United Nations Children's Fund Joint Program Monitoring service
ladder approach to national data collected in 2010/2011, we estimated the
national coverage of primary health centers (PHCs) (N = 8,831), auxiliary PHCs (N
= 22,853), village health posts (N = 28,692), and village maternity clinics (N =
14,396) with basic WASH services in Indonesia as part of a Sustainable
Development Goal baseline assessment. One quarter of PHCs did not have access to
a combination of basic water and sanitation (WatSan) services (23.6%) with
significant regional variation (10.6-59.8%), whereas more than two-third of PHCs
(72.0%) lacked handwashing facility with soap in all three locations (general
consulting room, immunization room, and delivery room). More than a half of the
three lower health service level facility types lacked basic WatSan services.
National health facility monitoring systems need to be urgently strengthened for
tracking the progress and addressing gaps in basic WASH services in health
facilities in Indonesia.
PMID- 29943725
TI - Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum
Malaria in Under-Five-Year-Old Nigerian Children Ten Years Following Adoption as
First-Line Antimalarials.
AB - The efficacies of 3-day regimens of artemether-lumefantrine (AL), artesunate
amodiaquine (AA), and dihydroartemisinin-piperaquine (DHP) were evaluated in 910
children < 5 years old with uncomplicated malaria from six geographical areas of
Nigeria. Parasite positivity 1 day and Kaplan-Meier estimated risk of persistent
parasitemia 3 days after therapy initiation were both significantly higher, and
geometric mean parasite reduction ratio 1 day after treatment initiation (PRRD1)
was significantly lower in AL-treated children than in AA- and DHP-treated
children. No history of fever, temperature > 38 degrees C, enrollment parasitemia
> 75,000 MUL-1, and PRRD1 < 5,000 independently predicted persistent parasitemia
1 day after treatment initiation. Parasite clearance was significantly faster and
risk of reappearance of asexual parasitemia after initial clearance was
significantly lower in DHP-treated children. Overall, day 42 polymerase chain
reaction-corrected efficacy was 98.3% (95% confidence interval [CI]: 96.1-100)
and was similar for all treatments. In a non-compartment model, declines of
parasitemias were monoexponential with mean terminal elimination half-life of 1.3
hours and unimodal frequency distribution of half-lives. All treatments were well
tolerated. In summary, all three treatments evaluated remain efficacious
treatments of uncomplicated malaria in young Nigerian children, but DHP appears
more efficacious than AL or AA.
PMID- 29943726
TI - Associations between Use of Antimalarial Medications and Health among U.S.
Veterans of the Wars in Iraq and Afghanistan.
AB - Mefloquine (Lariam(r); Roche Holding AG, Basel, Switzerland) has been linked to
acute neuropsychiatric side effects. This is a concern for U.S. veterans who may
have used mefloquine during recent Southwest Asia deployments. Using data from
the National Health Study for a New Generation of U.S. Veterans, a population
based study of U.S. veterans who served between 2001 and 2008, we investigated
associations between self-reported use of antimalarial medications and overall
physical and mental health (MH) using the twelve-item short form, and with other
MH outcomes using the post-traumatic stress disorder Checklist-17 and the Patient
Health Questionnaire (anxiety, major depression, and self-harm). Multivariable
logistic regression was performed to examine associations between health measures
and seven antimalarial drug categories: any antimalarial, mefloquine,
chloroquine, doxycycline, primaquine, mefloquine plus any other antimalarial, and
any other antimalarial or antimalarial combination while adjusting for the
effects of deployment and combat exposure. Data from 19,487 veterans showed that
although antimalarial use was generally associated with higher odds of negative
health outcomes, once deployment and combat exposure were added to the
multivariable models, the associations with each of the MH outcomes became
attenuated. A positive trend was observed between combat exposure intensity and
prevalence of the five MH outcomes. No significant associations were found
between mefloquine and MH measures. These data suggest that the poor physical and
MH outcomes reported in this study population are largely because of combat
deployment exposure.
PMID- 29943727
TI - Circulation of Influenza A(H5N8) Virus, Saudi Arabia.
AB - Highly pathogenic avian influenza A(H5N8) viruses have been detected in several
continents. However, limited viral sequence data are available from countries in
the Middle East. We report full-genome analyses of highly pathogenic H5N8 viruses
recently detected in different provinces in Saudi Arabia.
PMID- 29943728
TI - NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody
dependent cellular cytotoxicity.
AB - Antibodies acquired naturally through repeated exposure to Plasmodium falciparum
are essential in the control of blood-stage malaria. Antibody-dependent functions
may include neutralization of parasite-host interactions, complement activation,
and activation of Fc receptor functions. A role of antibody-dependent cellular
cytotoxicity (ADCC) by natural killer (NK) cells in protection from malaria has
not been established. Here we show that IgG isolated from adults living in a
malaria-endemic region activated ADCC by primary human NK cells, which lysed
infected red blood cells (RBCs) and inhibited parasite growth in an in vitro
assay for ADCC-dependent growth inhibition. RBC lysis by NK cells was highly
selective for infected RBCs in a mixed culture with uninfected RBCs. Human
antibodies to P. falciparum antigens PfEMP1 and RIFIN were sufficient to promote
NK-dependent growth inhibition. As these results implicate acquired immunity
through NK-mediated ADCC, antibody-based vaccines that target bloodstream
parasites should consider this new mechanism of action.
PMID- 29943729
TI - Optogenetic dissection of descending behavioral control in Drosophila.
AB - In most animals, the brain makes behavioral decisions that are transmitted by
descending neurons to the nerve cord circuitry that produces behaviors. In
insects, only a few descending neurons have been associated with specific
behaviors. To explore how descending neurons control an insect's movements, we
developed a novel method to systematically assay the behavioral effects of
activating individual neurons on freely behaving terrestrial D. melanogaster. We
calculated a two-dimensional representation of the entire behavior space explored
by these flies, and we associated descending neurons with specific behaviors by
identifying regions of this space that were visited with increased frequency
during optogenetic activation. Applying this approach across a large collection
of descending neurons, we found that (1) activation of most of the descending
neurons drove stereotyped behaviors, (2) in many cases multiple descending
neurons activated similar behaviors, and (3) optogenetically activated behaviors
were often dependent on the behavioral state prior to activation.
PMID- 29943732
TI - Disentangling the strings that organize behavior.
AB - The neurons that connect the brain and ventral nerve cord in fruit flies have
been mapped in unprecedented detail.
PMID- 29943731
TI - Temporal processing and context dependency in Caenorhabditis elegans response to
mechanosensation.
AB - A quantitative understanding of how sensory signals are transformed into motor
outputs places useful constraints on brain function and helps to reveal the
brain's underlying computations. We investigate how the nematode Caenorhabditis
elegans responds to time-varying mechanosensory signals using a high-throughput
optogenetic assay and automated behavior quantification. We find that the
behavioral response is tuned to temporal properties of mechanosensory signals,
such as their integral and derivative, that extend over many seconds.
Mechanosensory signals, even in the same neurons, can be tailored to elicit
different behavioral responses. Moreover, we find that the animal's response also
depends on its behavioral context. Most dramatically, the animal ignores all
tested mechanosensory stimuli during turns. Finally, we present a linear
nonlinear model that predicts the animal's behavioral response to stimulus.
PMID- 29943733
TI - The characterisation of hepatic mitochondrial function in patients with non
alcoholic fatty liver disease (NAFLD) using the 13C-ketoisocaproate breath test.
AB - : Hepatic mitochondrial function (HMF) assessed by the 13C-ketoisocaproate breath
test (13C-KICA BT) has been previously shown to be significantly associated with
the severity of biopsy proven non-alcoholic fatty liver disease (NAFLD). However,
it is uncertain whether any perturbation in HMF relates specifically to severity
of liver disease or factors associated with metabolic syndrome within (NAFLD).
Our aim was to investigate whether there was any change in HMF assessed by 13C
KICA BT in patients with NAFLD compared to control subjects, and to assess the
factors that are independently associated with HMF. METHODS: 77 patients with
NAFLD and 11 healthy control subjects were studied. HMF was assessed using 13C
KICA BT and expressed as cumulative % 13C-dose recovered on breath over 1 h (cPDR
over 1 h). Liver fat and fibrosis was assessed by transient elastography.
Multivariable linear regression modelling was undertaken to test the independence
of associations with HMF. RESULTS: HMF (cPDR over 1 h) was lower in NAFLD
compared to controls [13.4% (4.8) v. 21.0% (6.3); p < 0.0001)]. In NAFLD, HMF was
lower in patients with diabetes versus no diabetes [12.7% (3.4) v. 14.3% (6.1); p
= 0.003)]. Regression modelling showed age (beta = -0.08; p = 0.01), waist
circumference (beta = -0.08; p = 0.01), hip circumference (beta = -0.04; p =
0.01), aspartate aminotransferase (AST) (beta = -0.05; p = 0.01) and diabetes
status (beta = -1.81; p = 0.01) were independently associated with HMF (R2 =
41.5%; p < 0.0001). CONCLUSIONS: In patients with NAFLD (compared to healthy
subjects), there was a reduction in HMF assessed by the 13C-KICA BT. Furthermore,
in patients with NAFLD, HMF is independent and inversely associated with age,
waist and hip circumference, AST and diabetes status.
PMID- 29943734
TI - The effect of patent ductus arteriosus on pre-ductal and post-ductal perfusion
index in preterm neonates.
AB - OBJECTIVE: The ductus arteriosus is a blood vessel that connects the pulmonary
artery to the descending aorta during fetal life and generally undergoes
spontaneous closure shortly after birth. In premature neonates it often fails to
close (patent ductus arteriosus-PDA), which can result in diversion of a
significant part of the left-ventricular cardiac output to the pulmonary
circulation. This left-to-right shunt may result in significant increase of
pulmonary blood flow and decrease of systemic perfusion (hemodynamically
significant PDA-hsPDA), which may lead to severe neonatal morbidity. The study
objective was to find the relationship between hsPDA and perfusion index (PI), a
photoplethysmographic parameter related to systemic perfusion. APPROACH: PI
measures the relative systolic increase in tissue light absorption due to the
systolic increase in the tissue blood volume. PI has been found to be directly
related to tissue perfusion and is therefore expected to be affected by hsPDA.
MAIN RESULTS: PI was found to be higher in preterm neonates with hsPDA after
first week of life, in comparison to those with closed DA, despite the lower
systemic perfusion, probably due to reverse flow during diastole. SIGNIFICANCE:
In our study, perfusion index increased despite the lower systemic perfusion,
indicating that in neonates with hsPDA, perfusion index is not necessarily a
measure of perfusion. Nevertheless, PI can be used as a screening tool for
suspicious PDA, in order to select a relatively small group of neonates for a
more definitive examination by echocardiography, which is not suitable for
universal screening.
PMID- 29943730
TI - The functional organization of descending sensory-motor pathways in Drosophila.
AB - In most animals, the brain controls the body via a set of descending neurons
(DNs) that traverse the neck. DN activity activates, maintains or modulates
locomotion and other behaviors. Individual DNs have been well-studied in species
from insects to primates, but little is known about overall connectivity patterns
across the DN population. We systematically investigated DN anatomy in Drosophila
melanogaster and created over 100 transgenic lines targeting individual cell
types. We identified roughly half of all Drosophila DNs and comprehensively map
connectivity between sensory and motor neuropils in the brain and nerve cord,
respectively. We find the nerve cord is a layered system of neuropils reflecting
the fly's capability for two largely independent means of locomotion -- walking
and flight -- using distinct sets of appendages. Our results reveal the basic
functional map of descending pathways in flies and provide tools for systematic
interrogation of neural circuits.
PMID- 29943735
TI - A novel approach to brain connectivity reveals early structural changes in
Alzheimer's disease.
AB - OBJECTIVE: Recent studies have shown that complex networks along with diffusion
weighted imaging (DWI) can be efficient and promising techniques for early
detection of structural pathological changes in Alzheimer's disease. Besides,
connectivity studies, specifically assessing the organization of a graph and its
topology, could represent the best chance to discover how brain activity is
shaped and driven. Accordingly, we propose a methodology to evaluate how
Alzheimer's disease affects brain networks through a novel way to look at graph
connectivity. In fact, we use the combination of network features related to
brain organization with network features related to the variations in
connectivity between several subjects. APPROACH: From a DWI brain scan we
reconstruct a probabilistic tractography by evaluating the number of white matter
fibers connecting two anatomical districts, thus obtaining a weighted undirected
network. The nodes of this network are the cerebral regions provided by the
reference brain atlas, the weights are the intensity of linkage among them. We
investigated brain connectivity graphs retrieved from a set of 222 publicly
available DWI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI):
47 Alzheimer's disease (AD) patients, 52 normal controls (NC) and 123 mild
cognitive impairment (MCI) subjects, this latter cohort includes 85 early and 38
late MCI subjects, EMCI and LMCI respectively. MAIN RESULTS: The proposed brain
connectivity approach effectively characterizes Alzheimer's disease, especially
in its early stages. In fact, MCI is a prodromal phase of Alzheimer's disease. We
report a [Formula: see text] accuracy for the discrimination of NC and AD
subjects and accuracies of [Formula: see text] and [Formula: see text] for the
discrimination of MCI from respectively NC and AD subjects. SIGNIFICANCE: Our
complex network approach offers an innovative and effective instrument to model
brain connectivity and detect in DWI tractographies early changes due to
Alzheimer's.
PMID- 29943736
TI - Bone mineral density loss in patients with cirrhosis.
AB - Background/Aims: Evidence of increased risk of osteoporosis and osteopenia in
chronic liver disease and cirrhosis is inconsistent. This study aims to
investigate this relationship and to identify the predictors of increased loss of
bone mineral density in Saudi patients. Patients and Methods: One hundred and
sixty-four patients and controls who are age and gender matched, were included in
this study with 1:1 ratio. Patients' included in this study were adults with
confirmed liver cirrhosis. Bone mineral densitometry (BMD) at both lumbar spine
(LS) and femoral neck (FN) were collected for both groups. Univariate and
multivariate regression analyses were performed to identify predictors of BMD
loss. Results: Results showed that cirrhotic patients are at higher risk of
developing osteoporosis or osteopenia at LS (OR 2.23, 95% CI [1.19-4.19], P =
0.01) but not at FN, when compared to control sample. Patients with cirrhosis
were found to have lower vitamin D and PTH levels (P = 0.0005) and (P = 0.006),
respectively. Of the possible predictors tested (gender, age, body mass index
[BMI], phosphorus, calcium, parathyroid hormone (PTH), vitamin D, and Model for
End Stage Liver Disease [MELD] score), female gender was the main predictor of
loss of BMD at LS only (OR 4.80, 95% CI [1.47-15.73], P = 0.01). Conclusions: The
study showed that cirrhotic patients are at increased susceptibility of having
decreased BMD, particularly at the LS and it highlights the need for preventive
measures, especially for female patients.
PMID- 29943737
TI - Chronic nonbacterial osteomyelitis from a tertiary care referral center.
AB - Chronic nonbacterial osteomyelitis (CNO) is a little known autoinflammatory bone
disorder primarily affecting children and sometimes young adults. Diagnosis is
often delayed due to its varied and nonspecific initial symptoms. Very few cases
are reported from India. The aim of this report is to increase the awareness of
this disease among physicians, orthopedic surgeons, and rheumatologists. Four
male patients were diagnosed with CNO in the past 3 years. The age at onset
varied from 9 to 23 years with a median diagnostic delay of 3.5 years. All
patients presented with recurrent bony pain with or without localized swelling
over the affected bones. Two patients had previously undergone open surgical
procedures with bone biopsies and three patients had received at least one course
of antibiotics. Two patients responded well to nonsteroidal anti-inflammatory
drugs alone, one patient required a short course of glucocorticoids, and another
patient required methotrexate to control disease activity. This case series
includes males, onset at a relatively later age in most, and a longer diagnostic
delay. Thus, in addition to children and adolescents, CNO should be suspected in
young adults presenting with recurrent bony pain with or without localized
swelling.
PMID- 29943738
TI - Social capital, trust in health information, and acceptance of Measles-Rubella
vaccination campaign in Tamil Nadu: A case-control study.
AB - Background: Parents' decision about vaccination of children is influenced by
social relationships and sources of information. The aim of this study was to
assess the influence of social capital and trust in health information on the
status of Measles-Rubella (MR) vaccination campaign in Tamil Nadu. Materials and
Methods: This was a case-control study carried out in Kancheepuram district in
Tamil Nadu where the MR vaccination campaign offered by Government of Tamil Nadu
had poor acceptance. Cases were parents of children who had refused the MR
vaccine and controls were parents having children in the same age group who had
accepted the vaccine. Data on social capital and trust in health information were
collected by using social capital scale developed by the researchers and trust in
the source of information was measured by using simple questions on the level of
trust in the information source. Results: Nonadministration of MR vaccine was
high among young parents and parents of younger children. Vaccine acceptance was
higher when it was offered at school (P < 0.000) and also among parents who
trusted school teachers (P < 0.003) and other school children (P < 0.014) as
source of information. MR vaccine acceptance was less among parents who trusted
social media and WhatsApp information. Greater levels of health-related physical
social capital led to greater vaccine hesitancy. Multivariate analysis revealed
that greater the age of the child, better parental attitudes toward vaccination,
poorer health-related physical social capital, and greater trust in health
information provided by school teachers led to overall greater acceptance of the
MR vaccine. Conclusion: Strong homogeneous bonding social capital had a negative
influence on MR vaccine acceptance. Schools and school teachers played a vital
role in influencing parental decision to vaccinate.
PMID- 29943739
TI - Ureterocolic fistula diagnosed on the basis of diuretic renogram and direct
radionuclide cystography.
AB - Ureterocolic fistulae are a rare phenomenon and are most commonly seen secondary
to obstructive ureteric calculi. These are usually diagnosed on barium enema or
intravenous urography. Most of the times, more than one investigation is needed
to confirm the findings. We present a case of iatrogenically-induced ureterocolic
fistula, diagnosed on renogram and direct radionuclide cystography. This case
showcases the possibility of using a renogram study as a diagnostic tool for a
suspected ureterocolic fistula. A renogram study also enables to asess the renal
function, which is essential in deciding the management.
PMID- 29943740
TI - Moyamoya syndrome in hemoglobin E-beta thalassemia: A rare presentation and
association.
AB - Moyamoya disease is an idiopathic, nonatherosclerotic, noninflammatory, chronic
progressive cerebrovascular disease characterized by bilateral stenosis or
occlusion of the arteries around the circle of Willis, typically the supraclinoid
internal carotid arteries, followed by extensive collateralization, which are
prone to thrombosis, aneurysm, and hemorrhage. Secondary moyamoya phenomenon or
moyamoya syndrome (MMS) occurs in a wide range of clinical scenarios including
prothrombotic states such as sickle cell anemia, but the association with other
hemoglobinopathies is less frequently observed. We describe a case of a 25-year
old female with hemoglobin E-beta thalassemia who had a rare presentation of MMS
in the form of choreoathetoid movements in the left upper and lower extremities.
We describe this association, primarily to emphasize thalassemia as an extremely
rare but a potential etiology of MMS. Since MMS is a progressive disease, it is
important to diagnose and initiate treatment to prevent worsening of the disease
and recurrence of stroke.
PMID- 29943741
TI - Managing pulmonary embolism secondary to suppurative deep vein thrombophlebitis
due to community-acquired Staphylococcus aureus in a resource-poor setting.
AB - Deep vein thrombosis and pulmonary thromboembolism are rare and life threatening
emergencies in children. We report an 11-year old female who presented with acute
complaints of high grade fever, pain in the left thigh and inability to walk and
breathlessness since 6 days. On physical examination, there was a diffuse tender
swelling of the left thigh, tachypnea, tachycardia with hyperdynamic precordium
and bilateral basal crepitations. Ultrasonography and venous doppler of lower
limbs showed mild effusion of left hip joint and thrombus in the left common
femoral vein and left external iliac vein suggesting a diagnosis of septic
arthritis with thrombophlebitis. The tachypnea and tachycardia which was out of
proportion to fever and crepitations on auscultation prompted suspicion of an
embolic phenomenon. Radiograph of the chest revealed multiple wedge shaped
opacities in the right middle zone and lower zone suggestive of pulmonary
embolism and left lower zone consolidation. For corroboration, computed
tomography pulmonary angiography and computed tomography of abdomen was performed
which showed pulmonary thromboembolism and deep venous thrombosis extending up to
infrarenal inferior vena cava. On further workup, magnetic resonance imaging of
hips showed left femoral osteomyelitis and multiple intramuscular abscesses in
the muscles around the hip joint. Blood culture grew methicillin resistant
Staphylococcus aureus. Antibiotics were changed according to culture sensitivity
and there was a dramatic response. After four weeks of anticoagulation and
antibiotics the child became asymptomatic and thrombus resolved. Thus, it is
crucial to consider methicillin resistant Staphylococcus aureus infection as an
important infection when we encounter such a clinical scenario. This case report
highlights an unusual and potentially life threatening presentation of a virulent
strain of a common pathogen, which when diagnosed was completely amenable to
treatment.
PMID- 29943742
TI - Internet for child mental health: Boon or bane.
PMID- 29943743
TI - An unusual cause of respiratory distress.
AB - Exogenous lipoid pneumonia is a rare alveolar-filling disorder characterized by
foreign body reaction to inhaled/aspirated hydrocarbon that may be vegetable oil,
animal fat, or mineral oil. It is vanishingly rare and often missed except in the
classical clinical settings of acute aspiration of petroleum products. We present
a toddler with iatrogenic exogenous lipoid pneumonia and highlight clinical and
radiological clues that can prompt early recognition of this entity.
PMID- 29943744
TI - Efficacy of vitamin D supplementation in major depression: A meta-analysis of
randomized controlled trials.
AB - Background: There is a need to develop and periodically evaluate new treatment
strategies in major depression due to the high burden of nonresponse and
inadequate response to antidepressants. Aim: We aimed to assess the effect of
vitamin D supplementation on depression symptom scores among individuals with
clinically diagnosed major depression. Materials and Methods: Electronic search
of databases was carried out for published randomized controlled trials in
English language, peer-reviewed journals from inception till August 2017. Outcome
measure used for effect size calculation was depression symptom scores. Effect
sizes for the trials were computed using standardized mean difference (Cohen's
d), and I2 test was used to assess sample heterogeneity. Pooled mean effect sizes
were derived using both fixed and random-effects model. Critical appraisal of
studies was done using the Cochrane risk of bias assessment tool. Results: A
total of four trials involving 948 participants were included in the study. In
three trials, the intervention group received oral vitamin D supplementation
whereas in one parenteral vitamin D was given. Pooled mean effect size for
vitamin D supplementation on depressive symptom ratings in major depression was
0.58 (95% confidence interval, 0.45-0.72). The I2 value for heterogeneity was 0
suggesting low heterogeneity among studies. Egger plot intercept indicated
minimal publication bias. Conclusion: Vitamin D supplementation favorably
impacted depression ratings in major depression with a moderate effect size.
These findings must be considered tentative owing to the limited number of trials
available and inherent methodological bias noted in few of them.
PMID- 29943745
TI - Unconditional probability of dying and age-specific mortality rate because of
major non-communicable diseases in India: Time trends from 2001 to 2013.
AB - Background: Unconditional probability of dying because of four major non
communicable diseases (NCDs) between 30 and 70 years of age is the selected
global indicator to measure the impact of NCD prevention and control programs.
Objective: To calculate the unconditional probability of dying and age-specific
mortality rate because of major NCDs in India from 2001 to 2013. Methods: This
study used multiple data sources that are available in the public domain-Census
2001 and 2011, Sample Registration System, causes of death reports in 2001-03,
2004-06, and 2010-13. Unconditional probability of dying between ages 30 and 70
years during 2001, 2006, and 2013 was calculated by the formula suggested by the
World Health Organization. Line graphs were used to depict time trends in age
specific mortality rates over the years in four major NCDs (cardiovascular
diseases, cancer, diabetes, and chronic respiratory diseases). Results: The age
specific mortality rate because of four NCDs showed a decrease of 51 deaths per
100,000 population from 2001 to 2013. Of the four NCDs, age-specific mortality
rate was highest in cardiovascular diseases (238.2/100,000 population) and least
in diabetes mellitus (21.9/100,000 population); it was 76.3 and 58.2/100,000
population for cancer and chronic respiratory diseases, respectively. The
probability of dying was very less and was almost the same from 30 to 44 years of
life and increased steeply after that till 70 years of life; and it was more in
males (24%) compared with females (17.4%). Conclusion: Although India has shown a
decreasing trend in premature mortality because of NCDs in the past decade, the
rate of decrease is not on par to achieve the global "25 * 25" target.
PMID- 29943746
TI - Early presentation of ruptured post-traumatic hepatic artery pseudoaneurysm.
AB - Visceral artery aneurysms (VAA) are an uncommon but well recognized condition.
Hepatic artery aneurysms (HAA) represent 14-20% of all visceral artery aneurysms.
Post traumatic hepatic artery pseudoaneurysm is an uncommon delayed complication
of blunt liver trauma. Here we present a case of a 27 year old male with blunt
abdominal trauma who developed a post traumatic pseudoaneurysm of the hepatic
artery just proximal to its bifurcation into the left and right branches. The
pseudoaneurysm ruptured within 12 hours of injury and he required double ligation
of the hepatic artery as well as right and left hepatic arteries . However, the
bleeding continued through the retrograde flow from the gastroduodenal artery and
hence, ligation of gastrodudenal artery was also done. The decision of complete
devasularisation of liver was taken as an emergency lifesaving procedure. The
patient recovered and was discharged without sequel.
PMID- 29943747
TI - Tele-evidence: A videoconferencing tool as a viable alternative to physical
appearance of doctors for the judicial summons.
AB - Introduction: The role of physicians often extends beyond provision of direct
patient care and includes appearance in courts as professional or expert
witnesses to give their testimony in various legal cases. This often consumes
precious time and resources of the doctors and the hospitals. This study was
taken up to evaluate the present system of the physical appearance of the doctors
to various courts and compare it with the videoconferencing mode of giving
testimony (tele-evidence). Materials and Methods: Available records of summons
and vehicles used were analyzed to calculate the cost involved and man-hours
consumed in honoring the court summons. Telemedicine facility, available in our
institute, was used for conducting tele-evidence with selected courts of the two
states as a pilot, which was later expanded. A survey was also done to assess the
experience of the physicians with physical appearance and videoconferencing using
structured questionnaire after approval from the Institute's Ethics Committee.
Likert scale of 0-10 points was used to measure satisfaction. Results: There was
43% drop in the monthly mileage of vehicles, 49% reduction in the fuel cost per
month, and 28% savings in terms of time consumed for court duties. Satisfaction
score for parameters of time consumed, physical strain, mental strain,
communication with Honorable Judges, and overall experience was 87% through tele
evidence as compared to 31% with physical appearance. Conclusion: Tele-evidence
is an acceptable and implementable mode of testifying and has led to tremendous
resource savings in our tertiary care setting. The model needs to be replicated
for deliverance of justice and is in consonance with Government's push toward
Digital India.
PMID- 29943748
TI - Impact of climate change on occupational health and productivity: a systematic
literature review focusing on workplace heat.
AB - BACKGROUND: With climate change, mean annual air temperatures are getting hotter
and extreme weather events will become more and more common in most parts of the
world. OBJECTIVES: As part of the EU funded project HEAT-SHIELD we conducted a
systematic review to summarize the epidemiological evidence of the effects of
global warming-related heat exposure on workers' health and productivity.
METHODS: Three separate searches, focused, respectively, on: i) heat-related
illness (HRI), cardiovascular, respiratory and kidney diseases; ii) traumatic
injuries; and iii) vector-borne diseases or vectors distribution, were conducted
in PubMed. EMBASE was also consulted to retrieve relevant studies focused on the
health effects of climate change. A fourth search strategy to assess the effects
on work productivity was conducted both in PubMed and in the SCOPUS database.
RESULTS: A significant proportion of studies reported findings regarding the
Mesoamerican nephropathy issue. This is a disease occurring especially among
young and middle-aged male sugarcane workers, without conventional risk factors
for chronic kidney disease. For injuries, there is a reversed U-shaped exposure
response relationship between Tmax and overall daily injury claims. Outdoor
workers are at increased risk of vector-borne infectious diseases, as a positive
correlation between higher air temperatures and current or future expansion of
the habitat of vectors is being observed. As for productivity, agriculture and
construction are the most studied sectors; a day with temperatures exceeding 32
degrees C can reduce daily labour supply in exposed sectors by up to 14%.
CONCLUSIONS: The present findings should inform development of further research
and related health policies in the EU and beyond with regard to protecting
working people from the effects of workplace heat during climate change.
PMID- 29943749
TI - Occupational health and safety of road haulage company employees.
AB - BACKGROUND: This paper follows up on a project that was launched in 2008 and
contributed to the development of the new Italian Society of Occupational
Medicine (SIML) guidelines for the road haulage industry. OBJECTIVE: To reach a
better understanding of occupational illness amongst truck drivers, in order to
define appropriate health monitoring protocols and promote a healthy life-style.
METHODS: We assessed 673 male drivers (mean age 43.85 years, SD 9.56; mean
working seniority 27.28 years, SD 10.59), employed by 46 different companies. The
drivers, who were gradually recruited in the study over the years, had a maximum
of 8 re-assessments each, for a total of 2608 examinations. We applied a survey
protocol consisting in a medical examination, questionnaires for the most common
risks and instrumental and laboratory tests in compliance with SIML guidelines.
RESULTS: We identified a total of 44 work-related diseases: 22 cases of noise
induced hearing loss (NIHL) and 22 cases of lumbar degenerative disc disease. As
regards metabolic disorders, we observed 28 cases of diabetes mellitus, in most
cases (71.4%) as a first diagnosis or under poor therapeutic control. We observed
poorly-controlled hypertension in 103 drivers, the majority of whom (54%) were
diagnosed for the first time. Over 30% of the workers in our study were obese and
approximately 40% were tobacco smokers. We identified just 9 individuals (1.3%)
with a positive toxicological screening for use of recreational drugs. Our data
confirm a high prevalence of occupational illness amongst truck drivers.
Cardiovascular and metabolic conditions require close monitoring.
PMID- 29943750
TI - Falling asleep at the wheel and distracted driving. The High-Risk Professional
Drivers study.
AB - BACKGROUND: Sleepiness at the wheel and driving while engaged in other activities
are well known risk factors for traffic accidents. This article estimates the
prevalence of these factors among Italian Professional Drivers (PDs) and their
impact on reported driving mistakes. METHODS: A cross-sectional study was
conducted using anonymous questionnaires. PDs (n=497) were divided into two
groups: high-risk PDs (HiRis_PDs) (those who self-reported more than one incident
during the last 3 years and/or more than one mistake during the past year) and
non-HiRis_PDs (subjects who did not meet the above-mentioned inclusion criteria).
Logistic regression analyses were performed to assess the association of self
reported sleepiness and/or risky driving behaviour with the condition of being a
high-risk driver. RESULTS: 161 (32.4%) subjects were defined as HiRis_PDs. Forty
one percent of the interviewees experienced at least one episode per month of
sudden-onset sleep at the wheel. Twenty-eight point two percent reported a
regular use of a hand-held cell phone. Predictive factors for being HiRis_PDs
were: at least one self-reported episode per month of falling asleep at the wheel
[odds ratio (OR) 5, 95% confidence interval (CI) 3.21-7.80, P<0.001], driving
while regularly engaged in other activities (mainly hand-held cell phone use) (OR
6.11, 95% CI 2.90-12.84, P<0.001), and young age (OR 0.96, OR 1 year of age
increase, 95% CI 0.94-0.98, P=0.001). CONCLUSIONS: Focusing prevention efforts on
recognizing sleepiness at the wheel and on avoiding other distracting activities
while driving can reduce the possibility of driving errors on the road by about 5
6 times.
PMID- 29943751
TI - Stakeholders' views on vocational rehabilitation programs: a call for
collaboration with Occupational Health Physicians.
AB - BACKGROUND: The triple-dip recession taking place in Italy in 2008-2014 impacted
negatively on health, mainly by increasing the rate of unemployment. This
increased the prevalence of mental health disorders, while reducing the number of
available places on vocational rehabilitation programs (VRPs) delivered by the
psychiatric services. OBJECTIVES: To explore the different points of views of
stakeholders (namely, users and professionals) involved in VRPs developed inside
an Italian Community Mental Health Center (CMHC). METHODS: A sample of users,
psychiatrists, educators and nurses of an Italian CMHC involved in VRPs took part
in a focus group. Content analysis was performed with MAXQDA 12, by developing a
hierarchical code system a posteriori (i.e., derived from the data). The
respondent validation phase was carried out by means of a multiple-choice
questionnaire, administered to all participants. RESULTS: A total of 86 emerging
issues were coded, divided into two macro-areas: Positive and Negative
Reinforcements (48 contributions, 56%, and 38 contributions, 44%, respectively),
further subdivided into three areas: professional (service) factors, personal
(i.e, user-related) factors, and work environment features (including
relationships in the workplace). Some contributions raised issues concerning
occupational health protection (e.g. need of information about the rights and
duties of the users-workers, as well as the risks they are exposed to in the
workplace). CONCLUSIONS: The analysis suggested to address specific issues
concerning work and VRPs by means of psycho-education group interventions
currently carried out at CMHCs, and pointed to the need to foster collaboration
between mental health professionals and the occupational health physician of the
company where the VRP is started and where the user might be employed.
PMID- 29943752
TI - {Perception of alcohol problem among workers of the transportation, healthcare
and building sectors in the Lazio Region].
AB - AIM: To perform an analysis of the perception of alcohol use among workers of the
transportation, healthcare and building sectors. METHODS: A survey was carried
out on alcohol consumption and knowledge of deriving health effects. Socio
demographic characteristics of the workers were collected. Risk indexes for
habitual alcohol and binge consumption were calculated. RESULTS: The number of
workers entering the survey is 3,914 (57% males; 58% married). Two-thirds of the
sample reported good knowledge of alcohol-related risks that could occur at the
workplace, and 55% of alcohol-related health risks. Binge drinking is inversely
associated with female gender, good perceived health and good knowledge of
alcohol-related risks at the workplace and of alcohol-related health risks.
People who are single, young and working in the building sector show higher odds
for binge drinking. The habitual use is positively associated with marital status
(OR=1.51 for single) and working sector (in the building sector OR=3.28; in the
healthcare OR=1.90); and inversely associated with good health (OR=0.70), good
knowledge of alcohol-related risks at the workplace (OR=0.54) and of alcohol
related health risks (OR=0.41). CONCLUSIONS: Socio-demographic factors, such as
age, gender and marital status are associated with different patterns of alcohol
consumption, that in turn are inversely associated with good knowledge of alcohol
related risks at the workplace and of alcohol-related health risks. These results
suggest the need to increase knowledge of alcohol-related issues among the
workers, both at the workplace and in everyday life.
PMID- 29943753
TI - {Health and work after invasive heart procedures, rehabilitation and occupational
evaluation].
AB - BACKGROUND: Our previous experience with the "CardioWork" protocol (activated in
2005) demonstrated the usefulness of the interaction between occupational
physician and cardiologist to facilitate work resumption after invasive heart
procedures and subsequent rehabilitation, adapting the work tasks of the patients
to the changed physical capabilities. OBJECTIVES: We surveyed the health
conditions and employment status of the subjects previously studied, years after
their completion of the protocol in order to verify its effectiveness over a long
period of time. METHODS: We contacted 125 patients included in the protocol from
2005 to 2011: 4 were deceased; 101 (94 males and 7 females; mean age: 49.2 years)
participated in the study. We collected clinical data (from the hospital computer
archive), as well as information on prescriptions compliance and occupation (by
interview). Respondents were also asked to give a subjective judgment on their
health, their re-employment, and the usefulness of the indications regarding job
fitness. RESULTS: In addition to the high survival rate, the survey showed
maintenance of satisfactory clinical conditions (good left ventricular function,
exercise tolerance, rare cardiological relapses, few sick-leave days), adherence
to prescriptions, high employment rate, high level of subjective satisfaction.
CONCLUSIONS: The study confirms the importance of appropriate rehabilitation
after acute cardiac event, and the need for an interdisciplinary approach
involving the occupational physician. By following this strategy, patients not
only can return to work early, satisfactorily and with minimal risks, but they
also tend to keep their work and to reach retirement age in good health.
PMID- 29943754
TI - [Mobile miniature X-ray evaluation and pneumoconiosis: the role of the Clinica
del Lavoro in Milan (1941-1948)].
AB - Since the end of the 19th century, X-rays have been used to detect lung diseases.
In Italy, 207,096 miniature chest radiographs were taken from 1941 to 1948.
Traditional radiographs gave better results, but miniature chest radiographs were
useful for screening. Indeed, the development of mobile miniature chest
radiography units resulted in an improvement in mass X-rays screening for the
detection of penumoconiosis. These mobile miniature units were mounted on a bus
chassis, a solution that allowed to easily reach workers. The authors analyze
some models of X-ray wagon units used by the "Clinica del Lavoro" in Milan in the
1950s. From the point of view of medical museology, the preservation of these
devices requires appropriate spaces.
PMID- 29943756
TI - [Medication administration errors at an emergency service: knowing to decrease
risk].
AB - OBJECTIVE: TThere is a great potential risk of errors in the emergency services
and the studies carried out present heterogeneous results and methodology. The
aim was to calculate the prevalence and characteristics, types and consequences
for the patient, of medications administration errors in patients who attended
the emergency department (ED) of a tertiary hospital, and to propose improvement
strategies to prevent them. METHODS: A cross-sectional study of direct
observation in the emergency areas of internal medicine and observation of adult
patients was conducted in September 2016. Data collection was conducted by 4,
nursing professional's observers from the ED. Medication errors reported by
professionals to the hospital's voluntary reporting system were also analysed.
RESULTS: The number of medication administration errors observed was 150 (19%)
versus the number of medication administration errors reported to the hospital's
notification system, which was 14, from 2013 to 2016. The most frequent type of
error was incorrect administration rate (67%), followed by preparation errors
(16%) and incorrect time administration (14%). The medications that accumulated
the most errors were furosemide and methylprednisolone. None of the errors
involved damage to the patient. Descriptive statistics was used to summarize the
results of the study. CONCLUSIONS: The prevalence of medication administration
errors in the ED is high. Knowing about them is effective to undertake specific
improvement actions that may influence prevention, increasing patient safety.
PMID- 29943757
TI - [Analysis of the use of point-of-care ultrasonography in Emergency Departments in
public hospitals in Catalonia. ECURCAT Study].
AB - BACKGROUND: The aim of this study was to determine the degree of implantation,
the characteristics and the formation of point-of-care ultrasonography, performed
by emergency physicians in the public hospital emergency department (ED) of
Catalonia. METHODS: Descriptive study based on a survey conducted with those
responsible for the public ED in Catalonia and structured in three blocks:
difficulty of implementing the technique and perceived reasons for this
difficulty, equipment available in the emergency room and its use, and training
of emergency physicians. RESULTS: The survey was answered by 96.3% of public ED;
in 63.5% of them the emergency physicians performed point-of-care
ultrasonography. Implementing ultrasonography was considered to have a high
degree of difficulty in 86.5%, and 78.8% had their own ultrasound. The most
frequent use is abdominal (87.9%), thoracic (72.7%) and peripheral vascular
(69.7%). The presence of protocols and registers of the activity is scarce. The
training is not uniform between staff doctors and those on call. No significant
differences were found according to the type of hospital, the degree of activity
or the presence of a radiologist 24 hours a day, the exception being the FAST
protocol, which was more used in regional hospitals (89.5% vs. 42.9%; p=0.007).
CONCLUSIONS: Point-of-care ultrasonography done by emergency physicians is used
in more than half of the Catalan public ED. There is a need for extending the use
of ultrasound in the ED, it should be more regulated, appropriately registered
and involve all physicians working in the emergency department.
PMID- 29943755
TI - Electroacupuncture Inhibits Apoptosis of Peri-Ischemic Regions via Modulating
p38, Extracellular Signal-Regulated Kinase (ERK1/2), and c-Jun N Terminal Kinases
(JNK) in Cerebral Ischemia-Reperfusion-Injured Rats.
AB - BACKGROUND Previous studies suggested that inhibition of apoptosis prevents the
dysfunction of ischemia-reperfusion injury. In the pathogenesis of ischemia
reperfusion injury, JNK/ERK1/2 and p38 play an essential role in regulation of
cell apoptosis. Electroacupuncture (EA), a form of acupuncture, has demonstrated
superiority in preventing ischemia-reperfusion injury, but the underlying
mechanism is unclear. In the present study, we explored the effects of
electroacupuncture at Shenting (GV24) and Baihui (GV20) acupoints on focal
cerebral ischemia-reperfusion (MCAO) rats, and explored whether JNK/ERK1/2- and
p38-mediated cell apoptosis are involved. MATERIAL AND METHODS The rats were
divided into a sham operation control group, an ischemia group, and an
electroacupuncture group with acupuncture applied for 10 days (30 min per day).
TTC staining was used to calculate the ischemic brain volume. TUNEL staining and
transmission electron microscopy were used to detect cell apoptosis. Western blot
analysis and Bio-Plex were used to detect JNK, p38, ERK1/2, Bcl-2, and Bax
protein expression. RESULTS We found that electroacupuncture at day 10
significantly reduced cerebral infarction. In addition, electroacupuncture
suppressed activation of JNK and p38, while enhancing the activation of ERK1/2 in
the peri-ischemic regions. Consequently, the effect of electroacupuncture on
these pathways resulted in the inhibition of apoptosis, which was demonstrated by
TUNEL and transmission electron microscopy. We found that electroacupuncture
upregulated the anti-apoptotic Bcl-2/Bax ratio in peri-ischemic regions.
CONCLUSIONS Our findings suggest that inhibition of cell apoptosis via regulating
multiple signaling pathways might be a mechanism whereby electroacupuncture has a
positive therapeutic effect on post-stroke impairment.
PMID- 29943758
TI - [Appendicitis, an unusual cause of acute abdomen in neonatal patients. A case
report].
AB - Appendicitis is the most frequent surgical disease in childhood, but it is very
uncommon in the neonatal period. In this period of life, a delay in diagnosis
(frequently due to the rareness of this pathology and lack of clinical suspicion)
and consequently in therapeutic approach, frequently results in appendicular
perforation and a subsequently poor evolution of this pathology. We present the
case of a neonate with a history of Down's syndrome and Fallot's tetralogy. Due
to her basal cardiopathy, she required surgical intervention to create a systemic
pulmonary fistula, as a temporary bridge until definitive cardiac surgery could
be performed. In the postoperative period of this surgery she presented fever,
acute abdomen and abdominal radiography compatible with pneumoperitoneum. An
emergency laparotomy was performed, which revealed peritonitis secondary to a
cecal gangrenous appendix with perforation in its middle third. Neonatal
appendicitis is usually associated with diseases such as cystic fibrosis,
necrotizing enterocolitis, or Hirschsprung's disease, as in the case of our
patient. In neonates with acute abdomen and presence of pneumoperitoneum,
appendicitis must be part of the differential diagnosis and requires urgent
surgical intervention. Despite this, it presents a high rate of morbidity and
mortality. Once the definitive diagnosis is made, any basal pathology that
justifies its presence should be discarded.
PMID- 29943759
TI - [Quality of life in patients undergoing bariatric surgery: evolution and
determinants].
PMID- 29943760
TI - [Primary eosinophilic colitis in a celiac patient].
AB - Primary eosinophilic gastrointestinal disorders include a spectrum of
inflammatory chronic diseases in which eosinophils infiltrate the gut in the
absence of known causes of such tissue eosinophilia. They may affect any area of
the gastrointestinal tract although exclusive colonic disease is exceptional. Due
to their low prevalence these disorders are not usually taken into account when
making a differential diagnosis in a patient with chronic diarrhea, which is the
reason why in many cases the diagnosis can take many years. We describe the case
of a patient with well-controlled celiac disease and chronic diarrhea of
indeterminate origin. The final diagnosis was eosinophilic colitis. A complete
response was obtained when she was treated with oral budesonide. Nowadays she
remains asymptomatic.
PMID- 29943761
TI - [End of life care in Spanish intensive care units].
PMID- 29943762
TI - [Non-invasive diagnosis of cardiac amyloidosis due to transthyretin. Case
report].
AB - Amyloidosis due to deposits of transthyretin (ATTR) is currently considered the
most frequent form of cardiac amyloidosis and its incidence is increasing thanks
to the advances in diagnostic imaging techniques. Some non-invasive diagnostic
criteria have recently been published on this entity that due to the development
of new drugs for the specific treatment of cardiac ATTR, have prognostic and
therapeutic implications. That is why cardiac ATTR could cease to be a rare
disease and become a frequent one, and become potentially treatable instead of
incurable. We present the case of an 80-year-old male diagnosed with non
hereditary cardiac ATTR by means of gammagraphy with 99mTc diphosfonate
scintigraphy (99mTc-DPD) following the new criteria of non-invasive diagnosis.
PMID- 29943763
TI - [Let's educate the whole population in cardiopulmonary reanimation].
PMID- 29943764
TI - [Lethal interaction between 5-fluorouracil and brivudine].
PMID- 29943765
TI - [Laparotomy in a patient under opioid free anesthesia].
AB - Obese patients subjected to bariatric surgery have a high probability of
presenting complications that worsen with the use of opioids and can be reduced
thanks to anaesthetic techniques like opioid-free anaesthetics (OFA). The risk of
having to convert the laparoscopic surgical technique into open surgery is one of
the criticisms aimed at this anaesthetic modality, facing the possibility of
there not being a correct sympathetic or nociceptive control. We present the case
of a patient scheduled for laparoscopic bariatric surgery who, while maintaining
OFA, was converted to open surgery (exploratory laparoscopy), with correct
control achieved of both haemodynamics and perioperative pain.
PMID- 29943766
TI - [Defensive Medicine in Primary Care].
PMID- 29943767
TI - [Improvement in quality of life following bariatric surgery].
PMID- 29943768
TI - [An infant with intestinal pneumatosis and pneumoperitoneum: the difficult
decision not to intervene].
AB - Pneumoperitoneum in children may be due to causes that do not require urgent
surgery (cardiopulmonary resuscitation manoeuvres, severe respiratory pathology
or mechanical ventilation). Surgery in these cases could even worsen the
prognosis. We present the case of a male infant, ex-preterm, with a history of
necrotizing enterocolitis and ileal perforation at birth, requiring laparotomy
and intestinal resection on two occasions and developing a secondary microcolon,
due to disuse. At six months, after transitioning to full oral feeding, he
presented abdominal distension with extensive intestinal pneumatosis and
pneumoperitoneum on radiographs. His general appearance was good with normal
intestinal transit and no peritonitis. The patient remained fasting with
intravenous antibiotics, nasogastric decompression and parenteral nutrition. The
evolution was favourable with oral feeding restarting on the seventh day of
admission. The existence of pneumoperitoneum does not always require a laparotomy
and global assessment of the patient by an interdisciplinary health team may
avoid unnecessary aggressive treatments.
PMID- 29943769
TI - Use of Functional Foods and Oral Supplements as Adjuvants in Cancer Treatment.
AB - In cancer patients treated with radiotherapy to the abdominopelvic region,
dietary modifications and the use of functional foods (fortified food with added
ingredients to provide specific health improving benefits, such as antioxidants,
omega-3 fatty acids, and glutamine), may contribute to the improvement of the
toxic effects of treatment, including nausea, diarrhea, and constipation, among
others. With the aim of analyzing which coadjuvant foods benefit these patients,
scientific evidence was gathered by a group of experts. For these patients, the
authors recommend a diet that includes sufficient foods rich in antioxidants and
polyphenols instead of supplements. Docosahexaenoic and eicosapentaenoic acids
have proven useful for the management of anorexia/cachexia in pancreatic cancer
patients. Probiotics composed of Lactobacillus spp. and Bifidobacterium spp. are
regarded as safe even in patients with neutropenia and have been proven to
decrease gastrointestinal symptoms. Several factors should be considered before
probiotic supplementation, these include the stage of the disease, radiation
dose, and symptomatology of each patient. There is no demonstrated clear benefit
to the use of glutamine, so it is not recommended due to its high cost.
PMID- 29943770
TI - Nutrition in Patients with Cancer Treated with Chemo-radiotherapy to the
Abdominopelvic Area. A consensus report.
PMID- 29943771
TI - Epidemiological Profile, Gastrointestinal Toxicity, and Treatment of Pelvic
Cancers in Patients Managed with Radiotherapy to the Abdominal Pelvic Area.
AB - Mexico has seen an increase in cancer prevalence in its entire population as well
as particular age ranges, predominantly the older segment. The most frequently
reported pelvic cancers in Mexico are cervical, endometrial, bladder, prostate,
rectum, and anal canal. Approximately 80% of the population diagnosed with pelvic
cancers present with locally advanced tumors and require concomitant
chemoradiotherapy, sequential chemoradiotherapy, or radiotherapy alone. The
toxicity of any of these treatment modalities may be manifested as intestinal
injury, a significant problem that can compromise the response to treatment, the
patient's nutritional state, quality of life, and survival. In this article, we
will approach key aspects in nutrition as well as the epidemiological
characteristics and toxicities in patients affected by these pelvic tumors.
PMID- 29943772
TI - Nutritional Assessment Tools for the Identification of Malnutrition and
Nutritional Risk Associated with Cancer Treatment.
AB - Malnutrition and muscle wasting are common features of cancer cachexia that may
interfere with the patient's response to cancer treatment, survival, and quality
of life. An accurate nutritional screening at the time of diagnosis and
throughout the patient's treatment fosters better control of the disease. Several
screening tools have proven to be useful for this purpose. Nevertheless,
nutritional evaluation is not a routine practice in this clinical setting and
procedures must be standardized. Nutritional risk screening (NRS), malnutrition
screening tool (MST), and patient-generated subjective global assessment (PG-SGA)
are the most common screening tools, and each one possesses some benefits when
screening patients for malnutrition; however, weight loss over a specific time
period, dietary intake and anorexia must also be considered. The body mass index
adjusted weight loss grading system predicts survival. We recommend the
application of MST or NRS, followed by PG-SGA, food intake determination,
measurement of body weight, and its changes as well as body composition,
biochemical nutritional markers, muscle function, and physical performance.
PMID- 29943773
TI - Nutrient Recommendations for Cancer Patients Treated with Pelvic Radiotherapy,
with or without Comorbidities.
AB - Radiotherapy is one of the main treatment options used in pelvic cancers.
Ionizing radiation induces damage to surrounding tissues, resulting in disruption
of normal physiological functions and symptoms such as diarrhea, tenesmus,
incontinence, and rectal bleeding, which can all significantly alter the
patient's quality of life. These patients are at increased risk of developing
protein-calorie malnutrition and micronutrient deficiencies. Therefore, designing
a proper nutritional intervention plan, with an optimal proportion of protein,
fat, and carbohydrates, is required to reduce or even reverse the patients' poor
nutritional status, increase their tolerance and response to oncology treatment,
decrease the rate of complications and improve their quality of life. The aim of
this review was to establish a nutritional plan that includes recommendations on
macronutrient proportions and micronutrient intake in patients receiving pelvic
radiotherapy. The following nutritional plan has been recommended in the
literature: Energy: 28-31 kcal/kg/day, using the Harris-Benedict formula adjusted
for body weight in obese patients; protein: 20-30%; fat: 30-40%; and
carbohydrates: 40-50%. The maintenance of adequate levels of Vitamin D, Vitamin
E, Vitamin A, calcium, magnesium, thiamin, riboflavin, and niacin must be
emphasized. Physical activity must also be increased to maintain muscle mass.
Nutrient requirements must be established in an integral manner, considering the
patient's age, nutritional status, and the presence of comorbidities. Unnecessary
dietary restrictions should be avoided to ensure an adequate nutritional status.
PMID- 29943774
TI - Effects of Dietary Components During and After Concomitant Chemoradiotherapy,
Radiotherapy, or Sequential Chemoradiotherapy to the Abdominopelvic Area.
AB - Radiotherapy is a fundamental part of the treatment of pelvic neoplasms. Up to
90% of patients develop gastrointestinal symptoms as a result of acute injury to
the small and large intestine, particularly in the mucosa. Radiotherapy leads to
atrophy of the intestinal epithelium, acute crypt inflammation, inflammatory
infiltration of the epithelium, malabsorption of lactose, and biliary salts as
well as alterations in pancreatic enzymes and biliary salts, resulting in the
malabsorption syndrome and dysbiosis. The most commonly reported symptoms of
pelvic radiation disease include changes in bowel habits (94%), decreased fecal
consistency (80%), frequency of bowel movements (74%), bowel urgency (39%), and
fecal incontinence (37%). Although nutritional interventions with dietary
modifications have been reported to prevent and treat gastrointestinal symptoms,
the evidence remains inconclusive.
PMID- 29943775
TI - Epidemiological Data on the Nutritional Status of Cancer Patients Receiving
Treatment with Concomitant Chemoradiotherapy, Radiotherapy or Sequential
Chemoradiotherapy to the Abdominopelvic Area.
AB - Cancer patients are particularly susceptible to undernourishment so associated
weight loss is frequent. Approximately 15% of patients lose >10% of their usual
body weight, 40-80% become undernourished, and about 20% die as a result. Well
nourished patients have a higher survival rate when compared with patients at
risk of undernourishment (19.9 vs. 3.7 months); hence, nutritional intervention
is pivotal. Undernourishment negatively influences the patient's prognosis, and
its prevalence depends on the tumor type and location, disease stage, treatment,
and the applied nutritional evaluation tool. During abdominopelvic radiotherapy,
up to 90% of patients experience symptoms of varying severity; weight loss during
radiotherapy is an early indicator of nutritional deterioration, and he the use
of radiation is associated with a higher likelihood of undernourishment. In
patients with gynecological malignancies, 12.5-54% are malnourished before
receiving oncological treatment, worsening after treatment in 35.8-82% of cases.
There is also deterioration of the nutritional status in patients with colorectal
cancer once pelvic radiotherapy is initiated, whereby 50% of cases are
malnourished at the beginning of treatment, and 66.7% are so when it ends.
Although there are notable differences in the impact of radiotherapy on weight
according to the radiated region, 88% patients receiving abdominal radiotherapy
were found to lose weight compared to 38% of patients whose treatment was limited
to the pelvis.
PMID- 29943776
TI - A DNA-linker-DNA bifunctional probe for simultaneous SERS detection of miRNAs via
symmetric signal amplification.
AB - In this work, using a dual functional DNA-linker-DNA (DLD) probe, a new concept
of a symmetric signal amplification (SSA) reaction is introduced to
simultaneously analyze miRNAs. By coupling the surface-enhanced Raman scattering
(SERS) technology with symmetric amplification modes, this flexible biosensing
system exhibits high sensitivity and specificity.
PMID- 29943777
TI - Comparison of quenching mechanisms in Gd3Al5-xGaxO12:Ce3+ (x = 3 and 5) garnet
phosphors by photocurrent excitation spectroscopy.
AB - In this work we present the results of photocurrent excitation spectroscopy (PCE)
of Gd3Al2Ga3O12:Ce3+ (GAGG:Ce3+) and Gd3Ga5O12:Ce3+ (GGG:Ce3+) performed at
temperatures ranging from 100 to 500 K supplemented by spectroscopic measurements
(steady state and time resolved photoluminescence spectroscopy) performed at
temperatures ranging from 10 to 500 K and at high pressure up to 300 kbar. The
PCE spectra contain bands related to transitions from the ground state 2F5/2 of
the 4f1 electronic configuration to the crystal field split states related to the
5d1 electronic configuration of Ce3+. This implicates the presence of the
autoionization process - transfer of electrons from the localized, excited states
of Ce3+ to the conduction band (CB), directly linked to luminescence quenching of
Ce3+. The mechanism of autoionization of GAGG:Ce3+ and GGG:Ce3+ was determined to
be different on the grounds of differences in temperature dependence of
photocurrent intensity. The latter system exhibits autoionization, which occurs
when all of the 5d excited states are degenerated with the CB, whereas in the
former system, the autoionization process is thermally assisted with an
activation energy barrier (distance to the edge of the CB) of approximately 1600
cm-1. In GGG:Ce3+ the degeneracy of 5d1 states of Ce3+ was lifted by application
of high pressure, shifting the edge of the CB up and exposing Ce3+ luminescence
at 20 kbar. Further spectroscopic analyses of the pressure-temperature dependence
of the luminescence decay time as well as the temperature dependence of
photocurrent intensity of GGG:Ce3+ have independently shown existence of a
luminescence quenching state located approximately 600 cm-1 below the CB,
attributed to the impurity trapped exciton.
PMID- 29943778
TI - Electroformation of phospholipid giant unilamellar vesicles in physiological
phosphate buffer.
AB - Phospholipid Giant Unilamellar Vesicles (GUVs) are usually prepared by
electroformation in water, that is in a low-conductivity solution. We developed a
protocol allowing their electroformation in the most common physiological buffer,
phosphate-buffered saline (PBS). This was achieved based on a specific sequence
of increasing electrical fields and for the two usual electrode types for
electroformation, namely Indium Tin oxide-coated glass slides and Pt electrodes.
These GUVs are stable over time (hour time-scale) and they can be isolated or
micro-injected. The membrane composition was modified by adding cholesterol in
order to adjust its mechanical properties. The optimal proportion of cholesterol
vs. total phospholipid concentration was a ratio of 20 mol%, which increases
membrane rigidity and facilitates vesicle microinjection.
PMID- 29943779
TI - Drastic rearrangement of self-assembled hydrogen-bonded tapes in a molecular
crystal.
AB - A 2 : 1 hydrogen-bonded crystal of 2-pyrrolidone and chloranilic acid shows
structural phase transitions accompanied by the drastic rearrangement of hydrogen
bonded tapes. Such a phenomenon is attributed to the selective and directional
character of hydrogen bonds.
PMID- 29943781
TI - Influence of long-range forces and capillarity on the function of underwater
superoleophobic wrinkled surfaces.
AB - Underwater superoleophobic surfaces can be considered a particular type of
lubricant-infused surface, that have anti-fouling properties by virtue of a
trapped water layer that repels oils. However, as their function relies on a
water layer being trapped in the surface roughness, it is crucial to understand
the factors that determine the layer stability. In this work, the forces that are
responsible for the stability of thin liquid films within structured surfaces
were quantified, and the conclusions were tested against the performance of
wrinkled surfaces as underwater superoleophobic coatings. Here, the system
studied was a family of wrinkled surfaces made of hydrophilic poly(4
vinylpyridine) (P4VP), whereby the wrinkle width could be controllably tuned in
the range 90 nm to 8000 nm. The van der Waals free energy was quantified and the
capillary forces trapping water in the surface micro- and nano-wrinkle structure
were estimated. P4VP surfaces with micro-scale wrinkles had underwater
superoleophobic properties, and low adhesion to different oils with droplet roll
off angle below 6 degrees +/- 1 degrees . Despite the van der Waals free energy
of the system pointing to the dewetting of a water film under oil on top of a
smooth P4VP film, the wrinkled structure is sufficient to induce a Cassie state
with a trapped water layer. The micro-scale wrinkles (average width 4-12 MUm)
were found to be particularly effective in the trapping of the water in a Cassie
non-adhesive state. The P4VP wrinkled surfaces are superamphiphobic, as when they
were first infused with oil, and then exposed to a droplet of water under oil,
they exhibited superhydrophobic behavior. The P4VP wrinkles have the additional
useful feature of being transparent underwater, which makes them useful
candidates for the protection of underwater cameras and sensors.
PMID- 29943782
TI - Charge effects regulate reversible CO2 reduction catalysis.
AB - Modular but geometrically constrained ligands were used to investigate the impact
of key ligand design parameters (charge and bite angle) on CO2 hydrogenation and
formic acid dehydrogenation activity. These studies yielded an optimized catalyst
that achieved over 118 000 turnovers in CO2 hydrogenation, 247 000 turnovers in
HCO2H dehydrogenation, was applied in a hydrogen storage device used for 6 cycles
of hydrogen storage/release without requiring changes in pH or solvent, and
generated H2/CO2 gas at a pressure of 190 atm from formic acid.
PMID- 29943783
TI - Magnetic field modulated SERS enhancement of CoPt hollow nanoparticles with sizes
below 10 nm.
AB - It is well known that Pt shows much weaker plasmonic effects in the visible
spectrum when compared to Au, Ag and Cu. Therefore, the realization of efficient
optical absorption by Pt nanoparticles with sizes below 10 nm in the visible
spectrum remains a challenge. One possible way to enhance the optical absorption
is to prepare Pt-based bimetallic magnetic nanoparticles. Furthermore, if an
external magnetic field is applied, the synergistic effect of both electric and
magnetic fields may provide sufficient SERS enhancement. In this paper, CoPt
hollow nanoparticles (NPs) with sizes below 10 nm and ultrathin shells (~2 nm)
were synthesized in solution, at room temperature. The NPs have high surface-to
volume ratios and excellent structural stability. The hollow NPs exhibited
enhanced light absorption characterized by surface-enhanced Raman scattering
(SERS) with 4-mercaptobenzoic acid (4-MBA) as tip molecules. It is noted that the
SERS enhancement of these alloyed NPs can be tuned by using an external magnetic
field. A synergistic optical effect between these hollow NPs and the Ag film
substrate is obtained. Hence, CoPt hollow NPs show promise as SERS substrates and
potential for other applications in optical enhancement.
PMID- 29943784
TI - Native defect-assisted enhanced response to CH4 near room temperature by
Al0.07Ga0.93N nanowires.
AB - Gas sensors at low operating temperature with high sensitivity require group III
nitrides owing to their high chemical and thermal stabilities. For the first
time, Al0.07Ga0.93N nanowires (NWs) have been utilized in CH4 sensing, and it has
been demonstrated that they exhibit an improved response compared to GaN NWs at
the low operating temperature of 50 degrees C. Al0.07Ga0.93N NWs have been
synthesized via the ion beam mixing process using inert gas ion irradiation on
the bilayer of Al/GaN NWs. The sensing mechanism is explained with the help of
native defects present in the system. The number of shallow acceptors created by
Ga vacancies (VGa) is found to be higher in Al0.07Ga0.93N NWs than in as-grown
GaN NWs. The role of the O antisite defect (ON) for the formation of shallow VGa
is inferred from photoluminescence spectroscopic analysis. These native defects
strongly influence the gas sensing behaviour, which results in enhanced and low
temperature CH4 sensing.
PMID- 29943785
TI - The Auger process in multilayer WSe2 crystals.
AB - Multilayer WSe2 with a larger optical density of states and absorbance is
regarded as a better candidate than its monolayer counterpart for next generation
optoelectronic devices, however insight into carrier dynamics is still lacking.
Herein, we experimentally observed an anomalous PL quenching with decreasing
temperature for multilayer WSe2. At a low temperature (77 K), the Auger processes
govern carrier recombination in multilayer WSe2, which are induced by a phonon
bottleneck effect and strong photon absorption, and lead to PL quenching. From
transient absorption spectroscopy, two distinct Auger processes are observed: a
fast one (1-2 ps) and a slow one (>190 ps), which are caused by two different
deep midgap defect-levels in WSe2. Based on the Auger recombination model, these
two Auger rates are quantitatively estimated at ~6.69 (+/-0.05) * 10-2 and 1.22
(+/-0.04) * 10-3 cm2 s-1, respectively. Our current observations provide an
important supplement for optimizing the optical and electric behaviors in
multilayer WSe2 based devices.
PMID- 29943786
TI - Synergistic combination chemotherapy using carrier-free celastrol and doxorubicin
nanocrystals for overcoming drug resistance.
AB - A key challenge of chemotherapy in clinical treatments is multidrug resistance
(MDR), which mainly arises from drug efflux-induced tumor cell survival. Thus, it
is necessary to provide biocompatible chemotherapeutics to improve drug
accumulation in MDR cells. Herein, two clinical small molecular drugs, celastrol
(CST) and doxorubicin (DOX), were self-assembled into carrier-free and
biocompatible nanoparticles (CST/DOX NPs) via a simple and green precipitation
method for synergistic combination chemotherapy to overcome DOX resistance. These
spherical CST/DOX NPs can improve the water-solubility of CST, reduce the dosage
of DOX, and therefore significantly enhance cellular drug accumulation by
activating heat shock factor 1 (HSF-1) and inhibiting NF-kappaB to depress P-gp
expression, which results in apoptosis and autophagy of DOX resistant cells
through the ROS/JNK signaling pathway. Finally, synergistic combination
chemotherapy was attained in both MCF-7/MDR cells and 3D multicellular tumor
spheroids. Thus, CST/DOX NPs provide an alternative for overcoming drug
resistance in future clinical applications.
PMID- 29943788
TI - Suppression of exciton dephasing in sidewall-functionalized carbon nanotubes
embedded into metallo-dielectric antennas.
AB - Covalent functionalization of single-walled carbon nanotubes (SWCNTs) is a
promising route to enhance the quantum yield of exciton emission and can lead to
single-photon emission at room temperature. However, the spectral linewidth of
the defect-related E11* emission remains rather broad. Here, we systematically
investigate the low-temperature exciton emission of individual SWCNTs that have
been dispersed with sodium-deoxycholate (DOC) and polyfluorene (PFO-BPy), are
grown by laser vaporization (LV) or by CoMoCat techniques and are functionalized
with oxygen as well as 3,5-dichlorobenzene groups. The E11 excitons in oxygen
functionalized SWCNTs remain rather broad with up to 10 meV linewidth while
exciton emission from 3,5-dichlorobenzene functionalized SWCNTs is found to be
about one order of magnitude narrower. In all cases, wrapping with PFO-BPy
provides significantly better protection against pump induced dephasing compared
to DOC. To further study the influence of exciton localization on pump-induced
dephasing, we have embedded the functionalized SWCNTs into metallo-dielectric
antenna cavities to maximize light collection. We show that 0D excitons
attributed to the E11* emission of 3,5-dichlorobenzene quantum defects of LV
grown SWCNTs can display near resolution-limited linewidths down to 35 MUeV.
Interestingly, these 0D excitons give rise to a 3-fold suppressed pump-induced
exciton dephasing compared to the E11 excitons in the same SWCNT. These findings
provide a foundation to build a unified description of the emergence of novel
optical behavior from the interplay of covalently introduced defects,
dispersants, and exciton confinement in SWCNTs and might further lead to the
realization of indistinguishable photons from carbon nanotubes.
PMID- 29943789
TI - A fully verified theoretical analysis of strain-photonic coupling for quantum
wells embedded in wavy nanoribbons.
AB - For optoelectronic devices, an attractive research field involves the flexible
adjustment of the band gap in semiconductor quantum well (QW) structures by
strain engineering. However, rigid wafer-based technology enables lattice-misfit
strain during epitaxial growth, which is biaxial, unchangeable, and not
sufficient for the devices fitted on various irregular surfaces. Therefore,
exploiting the strain produced by externally deformed configurations offers
unique opportunities to continuously and non-defectively tune the QW's band
structure. Here, we propose a strategy to induce uniaxially distributed strain in
elaborately designed wavy quantum well nanoribbons (QWNRs). Meanwhile, a
numerically solved strain-photonic coupling model based on the theory of
elasticity and the eight-band k.p method is established to illustrate the strain
distribution coupled with the strain-induced band gap shift of the wavy QWNR. The
MU-photoluminescence measurements reveal a periodically varied band gap in the QW
along the uniaxial tensile direction, which is consistent with the result of
theoretical calculations. This model demonstrates the potential application of a
wrinkled configuration in arbitrarily controlling and tuning the band gap and
thus the optoelectronic performances of quantum well systems.
PMID- 29943790
TI - Hydrothermal synthesis of Bi2WO6 with a new tungsten source and enhanced
photocatalytic activity of Bi2WO6 hybridized with C3N4.
AB - Bi2WO6 nanosheets were synthesized by a hydrothermal method with H2WO4 for the
first time. The band structure of Bi2WO6 was investigated on the basis of density
functional theory calculations. Bi2WO6 photocatalysts showed photocatalytic
activity for the degradation of methylene blue under visible light irradiation.
Kinetic studies using radical scavenger technologies suggested that holes were
the dominant photo-oxidants. After hybridization with C3N4, the photocatalytic
activity of Bi2WO6 was obviously enhanced. The enhanced photocatalytic activity
of the C3N4/Bi2WO6 photocatalysts could be attributed to the effective separation
of photogenerated e-/h+ pairs. The photogenerated holes on the valence band of
Bi2WO6 can transfer to the highest occupied molecular orbital of C3N4via the well
developed interface, causing a reduction in the probability of e-/h+
recombination; consequently, large numbers of photogenerated holes led to the
enhancement of the photocatalytic activity.
PMID- 29943791
TI - Cargo carrying bacteria at interfaces.
AB - The displacements of ensembles of colloids at the interface between oil and
suspensions of the bacterium Pseudomonas aeruginosa PA14DeltapelA indicate
enhanced colloid mobilities and apparently diffusive motion driven by
interactions with the bacteria. However, inspection of individual trajectories of
~500 particles reveals prolonged, directed displacements inconsistent with purely
hydrodynamic interactions between swimming bacteria and colloids. Analysis of the
properties of colloid paths indicates trajectories can be sorted into four
distinct categories, including diffusive, persistent, curly, and mixed trajectory
types. Non-diffusive trajectories are the norm, comprising 2/3 of the observed
trajectories. Imaging of colloids in the interface reveals anisotropic assemblies
formed by colloids decorated with one or more adhered bacteria that drive the
colloids along these paths. The trajectories and enhanced transport result from
individual colloids being moved as cargo by these adhered bacteria. The
implications of these structures and open questions for interfacial transport are
discussed and related to the active colloid literature.
PMID- 29943792
TI - [Collecting stories with Ahmed and Ibrahim].
PMID- 29943793
TI - [New numbers on the duration of major and minor depressive episodes in the
general population; results from NEMESIS-2].
AB - BACKGROUND: Relatively little research has been conducted that can reliably be
used by psychiatrists, psychologists and general practitioners to estimate the
recovery time of their patients suffering from depression. The treatment
guideline for depression submits that half of those with mdd will recover within
three months.
AIM: To present the findings from nemesis-2 (the Netherlands
Mental Health Survey and Incidence Study-2) on both the duration of depressive
episodes in the general population and associated risk indicators.
METHOD:
The respondents that had developed a depressive episode between the first two
follow-up assessments were selected; 286 with a clinical depression according to
dsm-iv criteria (mdd) and 107 with a subclinical depression (MinDD). The episode
duration was assessed with the Life Chart Interview.
RESULTS: Half of the
patients with mdd recovered within 6 months and 12% had not recovered after 3
years. The mean duration for mdd was 10.7 months. Better physical and mental
health before depression onset predicted shorter duration. Longer duration was
associated with comorbid dysthymia or anxiety disorder. In comparison, the median
duration of MinDD was half the length of mdd (3 months), whereas the mean
duration (8.7 months), the percentage that had not recovered after 3 years (10%)
and risk indicators for episode duration hardly differed.
CONCLUSION: In
the guideline for depression it is assumed that half of those with mdd will
recover within three months. Our study, however, found the median duration of mdd
to be twice as long. Consequently, only a short period without active treatment
can be justified. This paper also concludes that MinDD cannot be regarded as a
transient, self-limiting mood state.
PMID- 29943794
TI - [Somatic and pharmacological nurse care in 2b-teams in Flanders: a cross
sectional explorative study].
AB - BACKGROUND: In the context of the Belgian mental health care reform (project
107), 2b-teams provide care to people with a serious mental illness (smi), a
population encountering regular somatic comorbidity and limited compliance with
medication. Team composition and care provided by these teams is rather
unclear.
AIM: To consider the team composition and to focus on the nurses'
role within Flemish 2b-teams. Also, seen from different disciplines involved, to
determine the desired future nursing role.
METHOD: A structured interview
was used to discover team characteristics and fidelity to the flexible assertive
community treatment (fact) model in 12 Flemish 2b-teams. With a digital survey
containing 16 questions we explored the actual and desired nursing care,
according to 151 nurses and medical physicians.
RESULTS: Despite the
difference in team size and composition, it was not found to be significant.
Flemish team's fact model-fidelity was average. Actual care was restricted to
psychosocial interventions. Regarding desired care, significant differences were
found between physicians and nurses. Caregivers within outreach teams scored
items significantly higher on desired care compared to actual care.
CONCLUSION: We conclude that the team composition of Flemish 2b-team varies, with
an average fact model fidelity. Team care is restricted to psychosocial
interventions, while more somatic and nursing care is desired.
PMID- 29943795
TI - [Belgian FACT teams: looking for assurance of good care].
PMID- 29943796
TI - [The effects of pharmacological and psychotherapeutic treatment of comorbid
anxiety disorders in patients with bipolar disorder].
AB - BACKGROUND: The co-occurrence of bipolar disorder and anxiety disorder is
associated with a worse prognosis. Clinical guidelines do not give clear
therapeutic recommendations on this subject.
AIM: To review the evidence on
the effectiveness of both psychotherapy and pharmacotherapy for anxiety disorders
in patients with a bipolar disorder.
METHOD: A systematic search in PubMed,
Embase, Cochrane en Psycinfo and subsequent screening of potential studies
resulted in 11 included studies.
RESULTS: Five studies examined the effect
of pharmacotherapy on treatment of comorbid anxiety disorders. One of these
studies showed that both olanzapine and lamotrigine provided positive results in
treating the anxiety disorders, with olanzapine being the more effective of the
two. Conflicting results were found for quetiapine and valproic acid. The
conclusion of one study was that risperidone was not effective. No studies were
found researching the effect of psychotherapy on treatment of comorbid anxiety
disorders. However, two case studies and four studies that included patients with
mixed diagnoses, including bipolar disorder, proposed evidence that behavioral
and cognitive behavioral therapy (cbt) had a positive effect on treatment of the
comorbid anxiety disorder.
CONCLUSION: There is little evidence on the
treatment of comorbid anxiety disorders in people with bipolar disorder.
Psychotherapy is preferred due to the uncertainty of the effects of
pharmacotherapy and the associated risk of causing side effects. Pharmacotherapy
can be considered in cases where this is insufficiently effective.
PMID- 29943797
TI - [Providing insight into the construct decisional conflict and its usability to
assess shared decision making].
AB - BACKGROUND: The increased attention for shared decision making (sdm) in mental
health care creates a need to evaluate its application. The construct decisional
conflict, which refers to the satisfaction of patients regarding both the
decision making process and the decisions made, could be of added value.
AIM: Clarifying decisional conflict and reflecting on its feasibility to evaluate
sdm in mental health care.
METHOD: A literature study exploring the
construct of decisional conflict was conducted, followed by a translation of the
results into a visual model.
RESULTS: Decisional conflict is a multi
dimensional construct and consists of factors influencing the decision making
process (information, support, values clarity), level of uncertainty concerning
the options and the quality of the decision making. Decisional conflict can be
illustrated by using a model and assessed with the Decisional Conflict
Scale.
CONCLUSION: Decisional conflict is informative and useful in the
evaluation of the application of sdm and improvement of the quality of the
decision making in mental health care as well. This is of importance since
patients who experienced less decisional conflict are more engaged in treatment
and show better clinical outcomes.
PMID- 29943798
TI - [Ten years of cognitive control training for depression: an overview of findings
and challenges].
AB - BACKGROUND: 2007 marks a shift in scientific literature on the cognitive
vulnerabilities of depression. Preceded by a vast amount of studies exploring
neuroplasticity and cognitive transfer effects, Siegle e.a. (Cognit Ther Res
2007; 31: 235-62) published the findings of a proof-of-principle study in which
cognitive control training (cct) was applied to treat depression. This denotes an
evolution towards clinically oriented cct studies targeting reduction of the
vulnerability mechanisms of depression. Following this publication, several
studies tested the effects of cct on emotional vulnerability. These studies show
great variability.
AIM: This article provides an overview summarizing the
findings of cct for depression published in the last 10 years.
METHOD: The
results of a recently conducted systematic review were reviewed, with a
particular interest in clinical implications and challenges.
RESULTS: cct
shows beneficial effects on indicators of depression vulnerability (e.g., stress
reactivity, rumination, symptomatology). Associated literature underlines the
importance of intensive training procedures, use of an affective task context and
task motivation.
CONCLUSION: cct shows potential as a clinical intervention
for depression. However, several questions still need to be addressed before
implementation into clinical practice is warranted.
PMID- 29943799
TI - [Child with extreme regression after migration and trauma].
AB - A 12-year-old boy in an asylum-seeking family suffered from extreme regression. A
few days after a minor traffic accident, he regressed to the developmental stage
of a young toddler. The rare diagnosis pervasive refusal syndrome (prs) was made.
This is considered to be an extreme form of a conversion disorder. We provided
multidisciplinary, supportive and stimulating treatment, taking into account
potentially influential factors. The boy recovered slowly, resuming adequate
functionality two years later. Additional reports of similar cases are necessary
to improve the knowledge on prs.
PMID- 29943800
TI - [Hypomania induced by intranasal corticosteroid fluticasone spray].
AB - A 79-year old man was diagnosed with an episode of hypomania during the use of
fluticasone intranasal spray. After discontinuation the patient recovered
completely. Patients with oral corticosteroid treatment have an increased risk of
developing severe neuropsychiatric symptoms. This case-report shows that adverse
systemic effects can also occur when using local corticosteroids. While the
incidence of systemic side effects after using local treatment is not well known,
there are various case reports. It is advised to be cautious when using multiple
corticosteroids simultaneously due to the additive effect, when treating risk
groups and when treating patients with a history of psychiatric disease.
PMID- 29943801
TI - Hospital-based phototherapy: What is the cost to our patients?
PMID- 29943802
TI - Influenza vaccine for chronic obstructive pulmonary disease (COPD).
AB - BACKGROUND: Influenza vaccinations are currently recommended in the care of
people with COPD, but these recommendations are based largely on evidence from
observational studies, with very few randomised controlled trials (RCTs)
reported. Influenza infection causes excess morbidity and mortality in people
with COPD, but there is also the potential for influenza vaccination to cause
adverse effects, or not to be cost effective. OBJECTIVES: To determine whether
influenza vaccination in people with COPD reduces respiratory illness, reduces
mortality, is associated with excess adverse events, and is cost effective.
SEARCH METHODS: We searched the Cochrane Airways Trials Register, two clinical
trials registries, and reference lists of articles. A number of drug companies we
contacted also provided references. The latest search was carried out in December
2017. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines
with placebo, either alone or with another vaccine, in people with COPD. DATA
COLLECTION AND ANALYSIS: Two review authors independently extracted data. All
entries were double-checked. We contacted study authors and drug companies for
missing information. We used standard methods expected by Cochrane. MAIN RESULTS:
We included 11 RCTs with 6750 participants, but only six of these included people
with COPD (2469 participants). The others were conducted on elderly and high-risk
individuals, some of whom had chronic lung disease. Interventions compared with
placebo were inactivated virus injections and live attenuated intranasal virus
vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal
live attenuated vaccine with intra-muscular inactivated vaccine and intranasal
placebo. Studies were conducted in the UK, USA and Thailand.Inactivated vaccine
reduced the total number of exacerbations per vaccinated participant compared
with those who received placebo (mean difference (MD) -0.37, 95% confidence
interval (CI) -0.64 to -0.11; P = 0.006; two RCTs, 180 participants; low quality
evidence). This was due to the reduction in 'late' exacerbations, occurring after
three or four weeks (MD -0.39, 95% CI -0.61 to -0.18; P = 0.0004; two RCTs, 180
participants; low quality evidence). Both in people with COPD, and in older
people (only a minority of whom had COPD), there were significantly more local
adverse reactions in people who had received the vaccine, but the effects were
generally mild and transient.There was no evidence of an effect of intranasal
live attenuated virus when this was added to inactivated intramuscular
vaccination.Two studies evaluating mortality for influenza vaccine versus placebo
were too small to have detected any effect on mortality. However, a large study
(N=2215) noted that there was no difference in mortality when adding live
attenuated virus to inactivated virus vaccination, AUTHORS' CONCLUSIONS: It
appeared, from the limited number of RCTs we were able to include, all of which
were more than a decade old, that inactivated vaccine reduced exacerbations in
people with COPD. The size of effect was similar to that seen in large
observational studies, and was due to a reduction in exacerbations occurring
three or more weeks after vaccination, and due to influenza. There was a mild
increase in transient local adverse effects with vaccination, but no evidence of
an increase in early exacerbations. Addition of live attenuated virus to the
inactivated vaccine was not shown to confer additional benefit.
PMID- 29943803
TI - Terlipressin versus placebo or no intervention for people with cirrhosis and
hepatorenal syndrome.
AB - BACKGROUND: Hepatorenal syndrome is a potentially reversible renal failure
associated with severe liver disease. The disease is relatively common among
people with decompensated cirrhosis. Terlipressin is a drug that increases the
blood flow to the kidneys by constricting blood vessels. The previous version of
this systematic review found a potential beneficial effect of terlipressin on
mortality and renal function in people with cirrhosis and hepatorenal syndrome.
OBJECTIVES: To assess the beneficial and harmful effects of terlipressin versus
placebo/no intervention for people with cirrhosis and hepatorenal syndrome.
SEARCH METHODS: We identified eligible trials through searches of the Cochrane
Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of
Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, and Science
Citation Index Expanded, and manual searches until 21 November 2016. SELECTION
CRITERIA: Randomised clinical trials (RCTs) involving participants with cirrhosis
and type 1 or type 2 hepatorenal syndrome allocated to terlipressin versus
placebo or no intervention. We allowed co-administration with albumin
administered to both comparison groups. DATA COLLECTION AND ANALYSIS: Two review
authors independently extracted data from trial reports and undertook
correspondence with the authors. Primary outcomes were mortality, hepatorenal
syndrome, and serious adverse events. We conducted sensitivity analyses of RCTs
in which participants received albumin, subgroup analyses of participants with
type 1 or type 2 hepatorenal syndrome, and Trial Sequential Analyses to control
random errors. We reported random-effects meta-analyses with risk ratios (RR) and
95% confidence intervals (CI). We assessed the risk of bias based on the Cochrane
Hepato-Biliary Group domains. We graded the quality of the evidence using GRADE.
MAIN RESULTS: We included nine RCTs with a total of 534 participants with
cirrhosis and ascites. One RCT had a low risk of bias for mortality and a high
risk of bias for the remaining outcomes. All included trials had a high risk of
bias for non-mortality outcomes. In total, 473 participants had type 1
hepatorenal syndrome. Seven RCTs specifically evaluated terlipressin and albumin.
Terlipressin was associated with a beneficial effect on mortality when including
all RCTs (RR 0.85, 95% CI 0.73 to 0.98; 534 participants; number needed to treat
for an additional beneficial outcome (NNTB) 10.3 people; low-quality evidence).
Trial Sequential Analysis including all RCTs also found a beneficial effect of
terlipressin. Additional analyses showed a beneficial effect of terlipressin and
albumin on reversal of hepatorenal syndrome (RR 0.63, 95% CI 0.48 to 0.82; 510
participants; 8 RCTs; NNTB 4 people; low-quality evidence). Terlipressin
increased the risk of serious cardiovascular adverse events (RR 7.26, 95% CI 1.70
to 31.05; 234 participants; 4 RCTs), but it had no effect on the risk of serious
adverse events when analysed as a composite outcome (RR 0.91, 95% CI 0.68 to
1.21; 534 participants; 9 RCTs; number needed to treat for an additional harmful
outcome 24.5 people; low-quality evidence). Non-serious adverse events were
mainly gastrointestinal, including diarrhoea (RR 5.76, 95% CI 2.19 to 15.15; 240
participants; low-quality evidence) and abdominal pain (RR 1.54, 95% CI 0.97 to
2.43; 294 participants; low-quality evidence).We identified one ongoing trial on
terlipressin versus placebo in participants with cirrhosis, ascites, and
hepatorenal syndrome type 1.Three RCTs reported funding from a pharmaceutical
company. The remaining trials did not report funding or did not receive funding
from pharmaceutical companies. AUTHORS' CONCLUSIONS: This review suggests that
terlipressin may be associated with beneficial effects on mortality and renal
function in people with cirrhosis and type 1 hepatorenal syndrome, but it is also
associated with serious adverse effects. We downgraded the strength of the
evidence due to methodological issues including bias control, clinical
heterogeneity, and imprecision. Consequently, additional evidence is needed.
PMID- 29943804
TI - Foley catheter silicone versus latex for term outpatient induction of labour: A
randomised trial.
AB - BACKGROUND: Both silicone and latex single-balloon Foley catheters are available
for cervical ripening but no literature exists to compare them. Local experience
suggested more frequent insertion-related accidental rupture of the membranes
(acROM) with silicone. AIMS: To compare the performance of silicone versus latex
catheters with respect to acROM and other outcomes. MATERIALS AND METHODS: Women
undergoing outpatient Foley catheter cervical ripening were randomised to a
silicone or latex catheter. Data were collected on the primary outcome, acROM,
and secondary outcomes including catheter insertion failure, unplanned hospital
admission and patient-reported discomfort, together with intrapartum fever and
antibiotics for suspected chorioamnionitis along with general obstetric and
neonatal outcomes. RESULTS: Among 534 recruited women, acROM was significantly
more common with a silicone compared to a latex catheter at 7.2% (19/265) versus
1.5% (4/269) (relative risk (RR) 4.8; 95% CI 1.7-14.0). Insertion failure was
significantly less common with silicone than latex at 2.6% (7/265) versus 9.3%
(25/269) (RR 0.3; 95% CI 0.1-0.6). However, when the alternative catheter was
subsequently tried, the final failure rates were 1.9% silicone (5/265) versus
2.6% latex (7/269). Insertion-related hospital admission was higher with silicone
at 9.4% (25/265) than latex at 4.8% (13/269) (RR 2.1; 95% CI 1.1-4.1). All other
obstetric outcomes were similar between the groups. CONCLUSION: When used for
cervical ripening, a silicone Foley catheter is associated with a higher rate of
acROM than a latex catheter but a lower rate of insertion failure. It may,
therefore, be reasonable to attempt insertion with a latex catheter initially and
manage insertion failures with a silicone catheter.
PMID- 29943805
TI - Perineal trauma with vaginal birth after a previous caesarean section: A
retrospective cohort study.
AB - BACKGROUND: There is a paucity of information regarding perineal injuries in
women who achieve vaginal birth after caesarean section (VBAC). AIMS: To
ascertain the rate of severe perineal injuries in women achieving VBAC at a major
tertiary obstetric hospital, and to determine if vaginal birth is more likely to
be associated with perineal injuries in women with one previous caesarean section
compared with nulliparous women. MATERIALS AND METHODS: A retrospective cohort
study was undertaken of women with singleton pregnancies at term who delivered
vaginally between 2013 and 2016. We compared nulliparous women with women who had
undergone one previous caesarean section. The primary outcome analysed was the
rate of third and fourth degree tears in each group. Secondary outcomes were
major post-partum haemorrhage and instrumental delivery. RESULTS: Totals of 10
663 nulliparous women and 629 VBAC women achieved vaginal birth. Of the VBAC
women, 418 achieved their first vaginal birth (first VBAC group). Overall, there
was no significant difference in the rate of third and fourth degree tears in the
VBAC group compared with the nulliparous group (6.0% vs 5.6%; P = 0.73). There
was no significant increase in anal sphincter injuries in the first VBAC group
compared with the nulliparous group (6.0% vs 7.4%; P = 0.25). CONCLUSION: No
overall difference in the rate of severe perineal injuries between VBAC women and
nulliparous women who achieve vaginal birth was observed in this study.
PMID- 29943806
TI - Fire in the theatre: A cautionary tale.
PMID- 29943807
TI - Poromas with large lumens histopathologically mimicking syringocystadenoma
papilliferum: Report of three cases.
AB - We report on three patients exhibiting tumours with exophytic pedunculated
structures with eroded surfaces. All cases showed the basic histopathological
features of poroma accompanied by large, invaginated ductal structures lined by
multiple layers of columnar or cuboidal cells. The columnar cells of invaginated
ductal/cystic structures focally exhibited subtle features reminiscent of
decapitation secretion along with dense infiltration of plasma cells in the
surrounding stroma, mimicking syringocystadenoma papilliferum.
PMID- 29943808
TI - Zerumbone inhibits epithelial-mesenchymal transition and cancer stem cells
properties by inhibiting the beta-catenin pathway through miR-200c.
AB - Colorectal cancer (CRC) is one of the most lethal and rampant human malignancies
in the world. Zerumbone, a sesquiterpene isolated from subtropical ginger, has
been found to exhibit an antitumor effect in various cancer types. However, the
effect of Zerumbone on the biological properties of CRC, including epithelial
mesenchymal transition (EMT) and cancer stem cells (CSCs) has not been fully
elucidated. Here, we investigated the inhibitory action of Zerumbone on the EMT
process, CSC markers, and the beta-catenin signaling pathway in the presence or
absence of miR-200c. The effect of Zerumbone on HCT-116 and SW-48 cells viability
was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
assay. The effects of Zerumbone on EMT-related genes, CSCs markers, cell
migration, invasion, sphere-forming, and beta-catenin signaling pathway were
explored. To evaluate the role of miR-200c in anticancer effects by Zerumbone,
miR-200c was downregulated by LNA-anti-miR-200c. Zerumbone significantly
inhibited cell viability, migration, invasion, and sphere-forming potential in
HCT-116 and SW-48 cell lines. Zerumbone significantly suppressed the EMT and CSC
properties as well as downregulated the beta-catenin. Silencing of miR200c
reduced the inhibitory effects of Zerumbone on EMT and CSCs in CRC cells. These
data indicated that Zerumbone may be a promising candidate for reducing the risk
of CRC progression by suppressing the beta-catenin pathway via miR-200c.
PMID- 29943809
TI - Eight-type human papillomavirus E6/E7 oncoprotein detection as a novel and
promising triage strategy for managing HPV-positive women.
AB - The management of HPV-positive women becomes particularly crucial in cervical
cancer screening. Here we assessed whether detection of E6 or E7 oncoproteins
targeting eight most prevalent HPV types could serve as a promising triage
option. Women (N = 1,416) aged 50-60 from Shanxi, China underwent screening with
HPV testing and liquid-based cytology (LBC), with any positive results referring
to colposcopy and biopsy if necessary. Women with HPV-positive results received
further tests using DNA-based genotyping, E6 or E7 oncoprotein detection
targeting HPV16/18 (for short: E6 (16/18) Test) or HPV16/18/31/33/35/45/52/58
(for short: E6/E7 (8 types) Test), respectively. Among HPV-positive women, E6/E7
(8 types) oncoproteins had lower positivity (17.37%) compared to DNA-based
genotyping for same eight types (58.30%) and LBC with ASC-US threshold (50.97%);
HPV16 was the genotype showing the highest frequency (8.49%) for oncoprotein
detection followed by HPV52 (3.47%), 58 (2.32%), 33 (1.54%), 18 (1.16%), 45
(0.77%), 35 (0.39%) and 31 (0%). For detection of cervical intraepithelial
neoplasia Grade 3 or higher (CIN3+), E6/E7 (8 types) Test had similar sensitivity
(100.00%) and superior specificity (85.94%) as well as positive predictive value
(PPV, 22.22%) compared to both LBC and DNA-based genotyping (8 types); For
detection of CIN2+, E6/E7 (8 types) Test was less sensitive (67.74%) but still
more specific (89.47%) and risk predictive with PPV of 46.67%. Notably, E6/E7 (8
types) Test remarkably decreased the number of colposcopies needed to detect one
CIN2+ and CIN3+ (2.14 and 4.50). E6/E7 oncoprotein detection showed a good "trade
off" between sensitivity and specificity with more efficient colposcopy
referrals, which is of great importance to maximize the benefits of HPV-based
screening program, especially applicable for the areas with high HPV prevalence
and low-resources.
PMID- 29943810
TI - Visual working memory load disrupts the space-based attentional guidance of
target selection.
AB - During visual search, the selection of target objects is guided by stored
representations of target-defining features (attentional templates). It is
commonly believed that such templates are maintained in visual working memory
(WM), but empirical evidence for this assumption remains inconclusive. Here, we
tested whether retaining non-spatial object features (shapes) in WM interferes
with attentional target selection processes in a concurrent search task that
required spatial templates for target locations. Participants memorized one shape
(low WM load) or four shapes (high WM load) in a sample display during a
retention period. On some trials, they matched them to a subsequent memory test
display. On other trials, a search display including two lateral bars in the
upper or lower visual field was presented instead, and participants reported the
orientation of target bars that were defined by their location (e.g., upper left
or lower right). To assess the efficiency of attentional control under low and
high WM load, EEG was recorded and the N2pc was measured as a marker of
attentional target selection. Target N2pc components were strongly delayed when
concurrent WM load was high, indicating that holding multiple object shapes in WM
competes with the simultaneous retention of spatial attentional templates for
target locations. These observations provide new electrophysiological evidence
that such templates are maintained in WM, and also challenge suggestions that
spatial and non-spatial contents are represented in separate independent visual
WM stores.
PMID- 29943811
TI - Author's reply to: Implementation and organization of cancer screening in France.
PMID- 29943812
TI - Inhaled corticosteroids in COPD and the risk of lung cancer.
AB - Inhaled corticosteroids (ICS) might reduce the risk of lung cancer by controlling
airway inflammation in patients with chronic obstructive pulmonary disease (COPD)
because both are associated with chronic inflammation. The objective was to
assess the impact of ICS on lung cancer risk reduction in COPD patients. We
performed a nested case-control study based on the database of the National
Health Insurance Service-National Sample Cohort, a nationally representative
cohort of 1,125,691 participants in Korea followed over 11 years. The eligible
population was patients aged 30-89 years who were newly diagnosed with COPD and
initiated inhaled medications after diagnosis. Cases were defined as individuals
diagnosed with lung cancer after the initiation of inhaled medications and were
matched with controls by propensity score at a 1:4 ratio. We identified 265
individuals with lung cancer, matched with 1,060 controls. Use of ICS was
associated with reduced risk of lung cancer (adjusted hazard ratio [aHR] 0.74,
95% CI 0.57-0.96). The high cumulative ICS dose group, defined as those above the
third quartile of ICS dose distribution, had a lower risk of lung cancer than the
low cumulative dose group (aHR 0.51, 95% CI 0.34-0.75). The effect of ICS on lung
cancer risk reduction was more remarkable in former smokers than current smokers.
Additionally, the result was consistent in men regardless of the classification
according to ICS use, while it was not significant in women. ICS, particularly at
high cumulative dose, might be associated with decreased risk of lung cancer in
patients with COPD. Severe COPD frequently warrants treatment with inhaled
corticosteroids, which exert immunomodulatory and antiproliferative effects.
Despite an association between COPD and increased lung cancer risk, patients on
ICS appear to have a reduced likelihood of developing lung cancer. Here,
analyzing data from the National Health Insurance Service-National Sample Cohort
in Korea, the authors show that ICS use is associated with decreased lung cancer
risk in COPD patients. An inverse dose-response relationship was detected,
whereby increasing cumulative ICS dose was associated with decreasing lung cancer
risk. The effect was most pronounced in men and former smokers.
PMID- 29943813
TI - Oxidative stress regulates autophagy in cultured muscle cells of patients with
chronic obstructive pulmonary disease.
AB - The proteolytic autophagy pathway is enhanced in the lower limb muscles of
patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen
species (ROS) have been shown to regulate autophagy in the skeletal muscles, but
the role of oxidative stress in the muscle autophagy of patients with COPD is
unknown. We used cultured myoblasts and myotubes from the quadriceps of eight
healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and
32.0%, respectively; p < 0.0001). We compared the autophagosome formation, the
expression of autophagy markers, and the autophagic flux in healthy subjects and
the patients with COPD, and we evaluated the effects of the 3-methyladenine (3
MA) autophagy inhibitor on the atrophy of COPD myotubes. Autophagy was also
assessed in COPD myotubes treated with an antioxidant molecule, ascorbic acid.
Autophagosome formation was increased in COPD myoblasts and myotubes (p = 0.011;
p < 0.001), and the LC3 2/LC3 1 ratio (p = 0.002), SQSTM1 mRNA and protein
expression (p = 0.023; p = 0.007), BNIP3 expression (p = 0.031), and autophagic
flux (p = 0.002) were higher in COPD myoblasts. Inhibition of autophagy with 3-MA
increased the COPD myotube diameter (p < 0.001) to a level similar to the
diameter of healthy subject myotubes. Treatment of COPD myotubes with ascorbic
acid decreased ROS concentration (p < 0.001), ROS-induced protein carbonylation
(p = 0.019), the LC3 2/LC3 1 ratio (p = 0.037), the expression of SQSTM1 (p <
0.001) and BNIP3 (p < 0.001), and increased the COPD myotube diameter (p <
0.001). Thus, autophagy signaling is enhanced in cultured COPD muscle cells.
Furthermore, the oxidative stress level contributes to the regulation of
autophagy, which is involved in the atrophy of COPD myotubes in vitro.
PMID- 29943814
TI - Cleavage of caspase-12 at Asp94, mediated by endoplasmic reticulum stress (ERS),
contributes to stretch-induced apoptosis of myoblasts.
AB - Mechanical overloading can lead to skeletal muscle damage instead of remodeling.
This is attributed to the excessive apoptosis of myoblasts, mechanism of which
remains to be elucidated. The present study aimed to investigate the involvement
of endoplasmic reticulum stress (ERS) and caspase-12 in mediating the stretch
induced apoptosis of myoblasts. Myoblast apoptosis was evaluated by Hoechst
staining, DNA fragmentation assay, Annexin V binding, and propidium iodide
staining, as well as caspase-3 and poly-ADP-ribose polymerase 1 cleavage. First,
our results showed that apoptosis was elevated in a time-dependent manner when
myoblasts were subjected to cyclic mechanical stretch (CMS) for 12, 24, and 36
hr. Concomitantly, CMS triggered the ERS and caspase-12 cleavage; ERS inhibitor
GSK 2606414 suppressed the CMS-induced cleavage of caspase-12 and myoblast
apoptosis. Silencing caspase-12 attenuated the apoptosis of myoblasts under CMS.
Furthermore, CMS-induced myoblast apoptosis was partially recovered by
overexpressing wild-type caspase-12 in caspase-12-silenced myoblasts. In
contrast, overexpressing mutant caspase-12 (D94N), which cannot be cleaved into
the active caspase-12 fragments, failed to accomplish the same effect. Finally,
C2C12 overexpressing truncated caspase-12 segment (TC-casp12-D94), which starts
from Asp94 and ends at Asn419, underwent apoptosis under both static and
stretched conditions. Interestingly, C2C12 myoblasts seemed to be resistant to
stretch-induced apoptosis upon low-serum-induced differentiation. In conclusion,
our study provided evidence that caspase-12 cleavage at Asp94, induced by ERS
under mechanical stimuli, is the key molecule in initiating the stretch-triggered
apoptosis of myoblasts.
PMID- 29943815
TI - Influence of all-trans retinoic acid on sperm metabolism and oxidative stress:
Its involvement in the physiopathology of varicocele-associated male infertility.
AB - The mechanisms by which varicocele affects fertility remain undetermined. Vitamin
A (all-trans retinoic acid [ATRA]) is required for fertility and normal
spermatogenesis; however, the mechanisms driving its action are not defined yet.
Previously, we demonstrated in varicocele sperm a reduced RARalpha expression and
that ATRA influence sperm performance. To further define vitamin A significance
in male gamete and in the physiopathology of varicocele, we tested for the first
time ATRA action on human sperm metabolism and antioxidant defense systems.
Evaluating triglycerides content and lipase activity, in normal sperm ATRA had a
lipid lowering effect, which was not observed in varicocele sperm. The modulation
of the glucose-6-phosphate dehydrogenase activity, concomitantly with a reduction
of the glucose content, highlight an ATRA role on glucose metabolism. ATRA
induced the superoxide dismutase (SOD) and glutathione transferase activities,
while it reduced the malondialdehyde and reactive oxygen species (ROS) production
both in healthy and varicocele sperm. Interestingly, SOD1 and SOD2 have been
localized in the acrosome and midpiece, glutathione- S-transferase omega 2
(GSTO2) in the acrosome, equatorial, and subacrosomial regions. SOD1, SOD2, and
GSTO2 levels were significantly lower in varicocele with respect to healthy
sperm. Herein, we discovered that ATRA treatment was able to reprogram sperm
metabolism toward that of the capacitation status. The retinol protected human
sperm from ROS damage enhancing the antioxidant enzymes activity, providing
evidence toward the efficacy of vitamin A as therapeutic tool in improving sperm
quality. These novel findings further confirm the importance of vitamin A in male
fertility adding new insights into the retinoids complex biological framework.
PMID- 29943816
TI - The Role of Quantitative Systems Pharmacology in the Design of First-in-Human
Trials.
PMID- 29943817
TI - PMLIV overexpression promotes TGF-beta-associated epithelial-mesenchymal
transition and migration in MCF-7 cancer cells.
AB - The epithelial-mesenchymal transition (EMT) is a key event associated with
metastasis and dissemination in breast tumor pathogenesis. Promyelocytic leukemia
(PML) gene produces several isoforms due to alternative splicing; however, the
biological function of each specific isoform has yet to be identified. In this
study, we report a previously unknown role for PMLIV, the most intensely studied
nuclear isoform, in transforming growth factor-beta (TGF-beta) signaling
associated EMT and migration in breast cancer. This study demonstrates that PMLIV
overexpression promotes a more aggressive mesenchymal phenotype and increases the
migration of MCF-7 cancer cells. This event is associated with activation of the
TGF-beta canonical signaling pathway through the induction of Smad2/3
phosphorylation and the translocation of phospho-Smad2/3 to the nucleus. In this
study, we report a previously unknown role for PMLIV in TGF-beta signaling
induced regulation of breast cancer-associated EMT and migration. Targeting this
pathway may be therapeutically beneficial.
PMID- 29943818
TI - Contemporary Issues in Women's Health.
PMID- 29943820
TI - Fibroblasts and mesenchymal stem cells: Two sides of the same coin?
AB - Mesenchymal stem/stromal cells (MSCs) have gained considerable popularity owing
to the vast possibilities and lack of ethical constraints and risks normally
associated with other stem cells, such as embryonic stem cells. However, they are
morphologically indistinguishable from fibroblasts. This review aims to assess
the similarities and differences between the two cell types, and the possible
relationship between them. We found that the two cells seem almost identical with
respect to their surface immunophenotype, proliferation, and differentiation
capacities and even, to an extent, their gene expression profiles and
immunomodulatory capacities. There are some differences in capability between the
two cells, with MSCs being more efficient than fibroblasts. Even so, the
similarities are so striking, that, if we were to follow the current criteria
provided by the International Society for Cellular Therapy, fibroblasts ought to
be named as MSCs. One promising marker is their DNA methylation profiles.
Nonetheless, without any other marker to differentiate between the cells in the
first place, it would be difficult to find a definitive marker. Interestingly,
the differences observed between the two cells have also been observed between
young and old MSCs. This also seems to be true of certain cell surface markers.
Therefore, it is possible that fibroblasts are in fact aged MSCs and that the two
cells are the same.
PMID- 29943819
TI - P2Y12 shRNA treatment decreases SGC activation to relieve diabetic neuropathic
pain in type 2 diabetes mellitus rats.
AB - Diabetic neuropathic pain is a common complication of type 2 diabetes mellitus
(DM). Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG)
plays a crucial role in neuropathic pain through the release of proinflammatory
cytokines. The P2Y12 receptor is expressed in SGCs of the DRG. In this study, our
aim was to investigate the role of the P2Y12 receptor on the pathological changes
in diabetic neuropathic pain. The present study showed that diabetic neuropathic
pain increased mechanical and thermal hyperalgesia in type 2 DM model rats. The
results showed that the expression levels of P2Y12 messenger RNA (mRNA) and
protein in DRG SGCs were increased in DM model rats compared with control rats.
Glial fibrillary acidic protein (GFAP) and interleukin-1beta (IL-1beta)
expression levels in the DRG were increased in DM rats. Upregulation of GFAP is a
marker of SGC activation. Targeting the P2Y12 receptor by short hairpin RNA
(shRNA) decreased the upregulated expression of P2Y12 mRNA and protein,
coexpression of P2Y12 and GFAP, the expression of GFAP, IL-1beta, and tumor
necrosis factor-receptor 1 in the DRG of DM rats, and relieved mechanical and
thermal hyperalgesia in DM rats. After treatment with the P2Y12 receptor shRNA,
the enhancing integrated OPTICAL density (IOD) ratios of p-P38 MAPK to P38
mitogen activated protein kinase (MAPK) in the DM rats treated with P2Y12 shRNA
were significantly lower than that in the untreated DM rats. Therefore, P2Y12
shRNA treatment decreased SGC activation to relieve mechanical and thermal
hyperalgesia in DM rats.
PMID- 29943821
TI - Management of intersex newborns: Legal and ethical developments.
AB - Countries worldwide are increasingly expanding male/female binary sex
classifications to recognize a third status. Intersex newborns may be included in
this third category on birth certification. Parents, families, and communities
require counselling and education to accommodate intersex newborns without stigma
or discrimination. Whatever its biological or genetic origin, intersex status is
a natural if relatively uncommon condition (one in 1500-2000 live births) that
distinguishes sex from gender. The tendency of societies to recognize only male
and female genders at birth has resulted in intersex children being subjected to
invasive surgery and related, sometimes lifelong, medication to confirm them as
male or female. On gaining maturity, some are severely distressed and resentful
that early gender assignment was mistaken, particularly when excision of testes
to enforce femininity or of ovaries to enforce masculinity has denied them
procreative capacity. Emerging principles support postponement of such
interventions until intersex individuals can make a gender choice for themselves.
PMID- 29943822
TI - Randomised study of HPV prevalence and detection of CIN2+ in vaginal self
sampling compared to cervical specimens collected by medical personnel.
AB - We conducted a randomised study to compare vaginal self-sampling with assisted
sampling by medical personnel on the cervix for HPV testing in primary screening.
The first aim was to determine if the HPV prevalence is independent of sampling
location (vagina versus cervix) and the person performing the sampling. The
second aim was to evaluate if the two sampling strategies differed in the
detection rate of CIN2+. In total, 19,523 women were randomised into two groups,
with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush
and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were
applied to the indicating FTA elute card and analysed for high-risk HPV using the
hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and
for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7%
of invited women participated in the study, as compared to 34.2% in the AS arm.
All samples contained sufficient amount of nuclear DNA for a valid HPV result,
with vaginal samples having a higher DNA amount than cervical samples (p < 4.62 *
10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 *
10-2 ), and the distribution of HPV types similar between arms. There was no
difference in the prevalence of CIN2+ per 1000 women screened between arms (p =
0.86). The results show that vaginal self-sampling is an equivalent alternative
to sampling by medical personnel for HPV typing and identification of CIN2+.
PMID- 29943823
TI - BMAL1 and CLOCK proteins in regulating UVB-induced apoptosis and DNA damage
responses in human keratinocytes.
AB - A diverse array of biological processes are under circadian controls. In mouse
skin, ultraviolet ray (UVR)-induced apoptosis and DNA damage responses are time
of-day dependent, which are controlled by core clock proteins. This study
investigates the roles of clock proteins in regulating UVB responses in human
keratinocytes (HKCs). We found that the messenger RNA expression of brain and
muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK)
genes is altered by low doses (5 mJ/cm2 ) of UVB in the immortalized HaCat HKCs
cell line. Although depletion of BMAL1 or CLOCK has no effect on the activation
of Rad3-related protein kinases-checkpoint kinase 1-p53 mediated DNA damage
checkpoints, it leads to suppression of UVB-stimulated apoptotic responses, and
downregulation of UVB-elevated expression of DNA damage marker gamma-H2AX and
cell cycle inhibitor p21. Diminished apoptotic responses are also observed in
primary HKCs depleted of BMAL1 or CLOCK after UVB irradiation. While CLOCK
depletion shows a suppressive effect on UVB-induced p53 protein accumulation,
depletion of either clock gene triggers early keratinocyte differentiation of
HKCs at their steady state. These results suggest that UVB-induced apoptosis and
DNA damage responses are controlled by clock proteins, but via different
mechanisms in the immortalized human adult low calcium temperature and primary
HKCs. Given the implication of UVB in photoaging and photocarcinogenesis,
mechanistic elucidation of circadian controls on UVB effects in human skin will
be critical and beneficial for prevention and treatment of skin cancers and other
skin-related diseases.
PMID- 29943824
TI - A new copper ionophore DPMQ protects cells against ultraviolet B irradiation by
inhibiting the TRPV1 channel.
AB - Copper is more likely than iron to generate reactive oxygen species (ROS) in a
redox reaction due to its higher electrochemical reactivity. This study examined
the effect of a newly synthesized Cu2+ binding compound, (E)-2-(4
(dimethylamino)phenylimino)methyl)quinolin-8-ol (DPMQ), on ultraviolet B (UVB)
irradiation-induced cytotoxicity in human dermal fibroblasts. DPMQ induced Cu2+
influx as effectively as disulfiram, a Cu2+ ionophore anticancer drug. However,
disulfiram induced ROS generation, mitochondrial dysfunction, and apoptosis in
fibroblasts in a Cu2+ -dependent manner, whereas DPMQ was not only nontoxic, but
protected cells against UVB irradiation-induced apoptosis in a Cu2+ -independent
manner. UVB irradiation induced a Ca2+ -dependent increase in ROS generation, a
decrease in Nrf2 levels, and activation of the mitochondrial apoptotic pathway,
and these effects were prevented by DPMQ, which also increased Nrf2 nuclear
translocation in a Cu2+ -independent manner. UVB irradiation activated 12
lipoxygenase and 12-hydroxyeicosatetraenoic acid (12-HETE), a product of 12
lipoxygenase, activated the TRPV1 channel. DMPQ did not act as a Ca2+ chelator,
but inhibited the cytosolic Ca2+ increase induced by 12-HETE or capsaicin, but
not that induced by bradykinin or ATP. Blockade of Ca2+ influx by pharmacological
inhibition or silencing of the TRPV1 channel or chelation of cytosolic Ca2+
inhibited the UVB irradiation-induced Nrf2 reduction, ROS generation,
mitochondrial dysfunction, and apoptosis. Taken together, our results suggest
that Ca2+ influx via the TRPV1 channel is responsible for UVB irradiation-induced
cytotoxicity and that DPMQ protects cells against UVB irradiation by inhibiting
the TRPV1 channel and stabilizing Nrf2, and could thus be a potentially useful
compound for the treatment of free radical-induced diseases.
PMID- 29943825
TI - Parent-offspring conflict over mate choice: An experimental study in China.
AB - Both parents and offspring have evolved mating preferences that enable them to
select mates and children-in-law to maximize their inclusive fitness. The theory
of parent-offspring conflict predicts that preferences for potential mates may
differ between parents and offspring: individuals are expected to value
biological quality more in their own mates than in their offspring's mates and to
value investment potential more in their offspring's mates than in their own
mates. We tested this hypothesis in China using a naturalistic 'marriage market'
where parents actively search for marital partners for their offspring. Parents
gather at a public park to advertise the characteristics of their adult children,
looking for a potential son or daughter-in-law. We presented 589 parents and
young adults from the city of Kunming (Yunnan, China) with hypothetical mating
candidates varying in their levels of income (proxy for investment potential) and
physical attractiveness (proxy for biological quality). We found some evidence of
a parent-offspring conflict over mate choice, but only in the case of daughters,
who evaluated physical attractiveness as more important than parents. We also
found an effect of the mating candidate's sex, as physical attractiveness was
deemed more valuable in a female potential mate by parents and offspring alike.
PMID- 29943827
TI - Implementation and organization of cancer screening in France.
PMID- 29943828
TI - Circular RNA circITGA7 inhibits colorectal cancer growth and metastasis by
modulating the Ras pathway and upregulating transcription of its host gene ITGA7.
AB - Circular RNAs (circRNAs) are significantly dysregulated in various cancer types.
However, the roles and mechanisms of circRNAs in cancer remain largely unknown.
In this study, we demonstrated that a novel circRNA (circITGA7) and its linear
host gene ITGA7 are both significantly downregulated in colorectal cancer (CRC)
tissues and cell lines. These decreased expression levels correlated with CRC
progression. Functional assays demonstrated that ectopic circITGA7 expression
suppressed the growth and metastasis of CRC cells in vitro and in vivo. Knockdown
of circITGA7 or ITGA7 promoted the proliferation and migration of CRC cells in
vitro, and enhanced CRC growth in vivo. Mechanistically, by using RNA-sequencing
and KEGG enrichment analysis, we found that circITGA7 is a negative regulator of
the Ras signalling pathway, and that ITGA7 is associated with cytokine-related
signalling pathways. In addition, circITGA7 binds to miR-370-3p to antagonise its
suppression of neurofibromin 1, which is a well-known negative regulator of the
Ras pathway. Finally, circITGA7 upregulates the transcription of ITGA7 by
suppressing RREB1 via the Ras pathway. In conclusion, our findings indicate a
suppressor role of circITGA7 and ITGA7 in CRC, and reveal that circITGA7 inhibits
the proliferation and metastasis of CRC cells by suppressing the Ras signalling
pathway and promoting the transcription of ITGA7, suggesting that circITGA7 is a
potential target for CRC treatment. Copyright (c) 2018 Pathological Society of
Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PMID- 29943826
TI - Coffee and tea consumption and risk of prostate cancer in the European
Prospective Investigation into Cancer and Nutrition.
AB - The epidemiological evidence regarding the association of coffee and tea
consumption with prostate cancer risk is inconclusive, and few cohort studies
have assessed these associations by disease stage and grade. We examined the
associations of coffee (total, caffeinated and decaffeinated) and tea intake with
prostate cancer risk in the European Prospective Investigation into Cancer and
Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed
over 14 years of follow-up. Data on coffee and tea consumption were collected
through validated country-specific food questionnaires at baseline. We used Cox
proportional hazards regression models to compute hazard ratios (HRs) and 95%
confidence intervals (CI). Models were stratified by center and age, and adjusted
for anthropometric, lifestyle and dietary factors. Median coffee and tea intake
were 375 and 106 mL/day, respectively, but large variations existed by country.
Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day)
consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94
1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer and 0.97
(95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease,
respectively. No evidence of association was seen for consumption of total,
caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or
cancer by stage, grade or fatality in this large cohort. Further investigations
are needed to clarify whether an association exists by different preparations or
by concentrations and constituents of these beverages.
PMID- 29943829
TI - Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in
multiple myeloma.
AB - Obesity has become a global epidemic influencing the establishment and
progression of a wide range of diseases, such as diabetes, cardiovascular
disease, and cancer. In 2016, International Agency for Research on Cancer
reported that obesity is now associated with 13 different cancers, one of which
is multiple myeloma (MM), a destructive cancer of plasma cells that predominantly
reside in the bone marrow. Obesity is the accumulation of excess body fat, which
causes metabolic, endocrine, immunologic, and inflammatory-like changes. Obesity
is usually associated with an increase in visceral and/or subcutaneous fat;
however, an additional fat depot that also responds to diet-induced changes is
bone marrow adipose tissue (BMAT). There have been several studies over the past
few decades that have identified BMAT as a key driver in MM progression.
Adipocytes secrete numerous adipokines, such as leptin, adiponectin, resistin,
adipsin, and visfatin, which when secreted at normal controlled levels have
protective properties. However, in obesity these levels of secretion change,
coupled with an increase in adipocyte number and size causing a profound and
lasting effect on the bone microenvironment, contributing to MM cell growth,
survival, and migration as well as potentially fueling bone destruction. Obesity
is a modifiable risk factor making it an attractive option for targeted therapy.
This review discusses the link between obesity, monoclonal gammopathy of
undetermined significance (a benign condition that precedes MM), and myeloma, and
the contribution of key adipokines to disease establishment and progression.
PMID- 29943830
TI - Social capital, health, health behavior, and utilization of healthcare services
among older adults: A conceptual framework.
AB - Meeting the health needs of Americans must change as the population continues to
live longer. A strategy that considers social well-being is necessary. One way to
improve social well-being is through increased social capital, which includes
networks among individuals and norms of reciprocity and trust between them.
Supporting attainment of bonding social capital from close-knit groups, such as
family, and bridging or linking social capital from those who are dissimilar are
vital. Research shows there is a relationship among social capital and self
reported mental and physical health, health behaviors, healthcare utilization,
and mortality. Because older adults are often dependent on others for their
healthcare needs, it is posited that social capital plays a key role. Nurses can
be instrumental in investigating levels of social capital for individuals and
determining what type of social support is needed and who in the individual's
network will provide that support. When support is absent, the nurse serves as
the link between patients and available resources. The purpose of this article is
to introduce a conceptual framework that can assist nurses and other healthcare
providers to consider social capital in older adults in the context of
relationships and the social environments to which they belong.
PMID- 29943832
TI - Lack of benefit Of 3,4-Diaminopyridine in MuSK+MG.
PMID- 29943831
TI - A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of
bevacizumab, with Avastin(r) (EU and US) in healthy male subjects.
AB - AIM: The aim of this study was to compare the pharmacokinetics (PK) of DRL_BZ
with that of EU-approved (reference medicinal product; RMP) and US-licensed
(reference product; RP) bevacizumab (Avastin(r) ) in healthy male subjects.
METHODS: In this double-blind, parallel-group, Phase 1 study (BZ-01-001), men
aged 20-45 years were randomized 1:1:1 to receive a single intravenous infusion
of 1 mg kg-1 of bevacizumab as DRL_BZ, RMP or RP. A total of 149 subjects were
randomized (DRL_BZ, 50; RMP, 50; RP, 49). Primary endpoints included maximum
observed serum concentration (Cmax ), area under the concentration-time curve
from time zero (pre-dose) extrapolated to infinity (AUC(0-infinity) ), and area
under the concentration-time curve from time zero (pre-dose) to last quantifiable
concentration (AUC(0-t) ). Secondary objectives were to compare the safety and
immunogenicity of DRL_BZ with those of the reference products. RESULTS: Primary
PK parameters were comparable across groups, and 90% confidence intervals for the
geometric mean ratios of the primary PK endpoints were within the pre-specified
equivalence margins (80-125%) for all pairwise comparisons (DRL_BZ vs. RMP,
DRL_BZ vs. RP and RMP vs. RP). No deaths or serious adverse events were reported.
Similar numbers of subjects reported similar numbers of treatment-emergent
adverse events in the three treatment groups. One subject who received DRL_BZ had
anti-drug antibodies at the Day 85 visit; however, no anti-drug antibodies were
detected in this subject at the 12-month follow-up visit. CONCLUSIONS: PK, safety
and immunogenicity of DRL_BZ were comparable to EU-approved and US-licensed
bevacizumab in healthy male subjects.
PMID- 29943833
TI - The basal interstitial nucleus (BIN) of the cerebellum provides diffuse ascending
inhibitory input to the floccular granule cell layer.
AB - The basal interstitial nucleus (BIN) in the white matter of the
vestibulocerebellum has been defined more than three decades ago, but has since
been largely ignored. It is still unclear which neurotransmitters are being used
by BIN neurons, how these neurons are connected to the rest of the brain and what
their activity patterns look like. Here, we studied BIN neurons in a range of
mammals, including macaque, human, rat, mouse, rabbit, and ferret, using tracing,
immunohistological and electrophysiological approaches. We show that BIN neurons
are GABAergic and glycinergic, that in primates they also express the marker for
cholinergic neurons choline acetyl transferase (ChAT), that they project with
beaded fibers to the glomeruli in the granular layer of the ipsilateral floccular
complex, and that they are driven by excitation from the ipsilateral and
contralateral medio-dorsal medullary gigantocellular reticular formation.
Systematic analysis of codistribution of the inhibitory synapse marker VIAAT, BIN
axons, and Golgi cell marker mGluR2 indicate that BIN axon terminals complement
Golgi cell axon terminals in glomeruli, accounting for a considerable proportion
( > 20%) of the inhibitory terminals in the granule cell layer of the floccular
complex. Together, these data show that BIN neurons represent a novel and
relevant inhibitory input to the part of the vestibulocerebellum that controls
compensatory and smooth pursuit eye movements.
PMID- 29943834
TI - Behavior management in the field of nursing: A concept analysis.
AB - AIM: This concept analysis is to clarify what behavior management in the field of
nursing means, what attributes signify it, and what its antecedents and
consequences are. BACKGROUND: A variety of definitions of behavior management
were identified in literature. This has resulted in a degree of confusion in the
way behavior management is described. METHODS: The Walker and Avant concept
analysis approach was applied. Literature searches were conducted using CINAHL,
Academic Search Complete, Business Source Complete, Communication and Mass Media
Complete, Education Research Complete, PubMed Medline, Google Scholar and many
online dictionaries, with timeline from January 2000 to November 2017. FINDINGS:
The analysis demonstrates that the concept of behavior management in nursing
field has two core attributes: (a) conscious actions to maintain and promote
positive activities, and (b) training and assisting from the person who has
knowledge and experience. Antecedents include poor general knowledge, lack of
ability to control, and personality. Consequences include an improvement of
quality and productivity and quality of life, reduction of mortality rate of
diseases, and development of pro-social skills for the youth. CONCLUSION: The
analysis helps nurses to understand the concept and its application into clinical
practice as well as to develop appropriate intervention plans for patients.
PMID- 29943835
TI - Itching at night: A review on reducing nocturnal pruritus in children.
AB - The most common causes of chronic nocturnal itching in children are atopic
dermatitis and psoriasis, with lichen simplex chronicus and prurigo nodularis
contributing to lesser degrees. Despite the prevalence of nocturnal itching, its
pathophysiology remains poorly understood. The most troubling consequence of
itching at night is poor quality of sleep. Poor sleep quality in children with
nocturnal itching has been linked to adverse neurocognitive, behavioral, and
physiologic outcomes, including poor performance in school, attention deficit
hyperactivity disorder, short stature, hypertension, obesity, and impaired immune
function. There is no consensus on the best management of nocturnal itching in
children. We conducted a review of the literature evaluating the efficacy of
various treatment options for children with chronic nocturnal pruritus. Our
review found three recently conducted randomized controlled trials and one case
report demonstrating the efficacy of topical corticosteroids, oral melatonin, and
clonidine in reducing nocturnal itching or improving sleep quality in children
with nocturnal pruritus. Future research is needed to elucidate the
pathophysiology of nocturnal itching to best develop targeted, effective
treatment strategies.
PMID- 29943836
TI - Forkhead-box R2 promotes metastasis and growth by stimulating angiogenesis and
activating hedgehog signaling pathway in ovarian cancer.
AB - Overexpression of forkhead-box R2 (FoxR2) is related to metastasis and
progression of tumor. However, its biological functions in ovarian cancer (OC)
progression remain unclear. Herein, we aimed to explore the changes in biological
functions and molecular events related to FoxR2 overexpression. We found that
FoxR2 is upregulated frequently in OC where these events are associated with
worse histologic grade and poor survival. Enhanced expression of FoxR2 was
related to cell growth, migration, and epithelial-mesenchymal transition, whereas
silencing of FoxR2 suppressed these malignant phenotypes. In addition,
angiogenesis was stimulated by FoxR2 overexpression by enhancing vascular
endothelial growth factor expression. Further mechanistic investigations revealed
that the increase in cell surface FoxR2 promoted sonic hedgehog binding and
signaling. Inhibiting hedgehog pathway with sonidegib decreased FoxR2-induced
migration and lung metastasis of OC cells, establishing the critical role of
hedgehog signaling in mediating the effects of FoxR2 expression. Taken together,
our results indicate that FoxR2 overexpression in OC contributes to malignant
behavior in cancer cells, at least in part through stimulating angiogenesis and
activation of the hedgehog signaling pathway. Hedgehog signaling pathway
activation may be the key in tumor progression mediated by FoxR2.
PMID- 29943837
TI - Bier anaemic spots, cyanosis with urticaria-like eruption (BASCULE) syndrome on
trunk and upper limbs.
AB - Bier anaemic spots, cyanosis with urticaria-like eruption syndrome is a recently
described benign vasomotor dermatosis that mainly affects the lower limbs.
Histopathology shows multiple dilated dermal vessels with scattered eosinophils.
We report a case on the trunk and upper limbs.
PMID- 29943838
TI - Onychomycosis in children: Safety and efficacy of antifungal agents.
AB - Onychomycosis is an uncommon condition in childhood, but prevalence in children
is increasing worldwide.The objective was to review the efficacy and safety of
systemic and topical antifungal agents to treat onychomycosis in children.
Databases (Pubmed, OVID, Scopus, clinicaltrials.gov, Cochrane Library) were
searched. Seven studies were selected for inclusion. Only one was a randomized
controlled trial. In total, 208 children were administered antifungal agents for
the treatment of onychomycosis. Four reports of mild adverse events were
documented (1.9% of treated children), one of which discontinued treatment
(0.5%). Limitations of this review are the lack of randomized controlled trials
available in pediatric onychomycosis. These findings suggest that antifungal
therapies used to treat onychomycosis in children are associated with a low
incidence of adverse events. Current dosing regimens for antifungal drugs are
effective and appear safe to use in children, notwithstanding that the Food and
Drug Administration has not approved any of these agents for the treatment of
onychomycosis in children. To our knowledge, this review is the most up-to-date,
comprehensive summary of pediatric onychomycosis treatment.
PMID- 29943840
TI - Let's think again about using mammalian temperature-sensitive mutants to
investigate functional molecules-The perspectives from the studies on three
mutants showing chromosome instability.
AB - This review evaluates the use of temperature-sensitive (ts) mutants to
investigate functional molecules in mammalian cells. A series of studies were
performed in which mammalian cells expressing functional molecules were isolated
from ts mutants using complementation by the introduction and expression of the
responsible protein tagged with the green fluorescent protein. The results showed
that chromosome instability and cell-cycle arrest were caused by ts defects in
the following three molecules: the largest subunit of RNA polymerase II, a
protein involved in splicing, and ubiquitin-activating enzyme. The cells
expressing functional protein were then isolated by introducing the responsible
gene tagged with the green fluorescent protein to complement the ts phenotype.
These cells proved to be useful in analyzing the dynamics of RNA polymerase II in
living cells. Analyses of the functional interaction between proteins involved in
splicing were also useful in the investigation of ts mutants and their
derivatives. In addition, these cells demonstrated the functional localization of
ubiquitin-activating enzyme in the nucleus. Mammalian ts mutants continue to show
great potential to aid in understanding the functions of the essential molecules
in cells. Therefore, it is highly important that studies on the identification
and characterization of the genes responsible for the phenotype of a mutant are
carried out.
PMID- 29943839
TI - The impact of burnout on self-efficacy, outcome expectations, career interest and
nurse turnover.
AB - AIMS: To examine the impact of burnout on self-efficacy, outcome expectations,
career interest and on nurses' intentions to leave the profession and to leave
the organization. BACKGROUND: Burnout is associated with nurse turnover. Research
clarifying the underlying mechanism may provide a novel means to mitigate the
impact of burnout on nurse turnover. DESIGN: This study uses a cross-sectional
design and proportionate stratified sampling. METHODS: Data were collected from a
sample of nurses in one medical centre in northern Taiwan during February - March
2017. This study included nurses employed full-time at the medical centre.
Burnout was measured using Maslach Burnout Inventory-Human Service Survey. Self
efficacy, outcome expectations and career interest were measured using the scale
of Cunningham et al. Intentions to leave were measured using the scales of Teng
et al. Structural equation modelling was used to assess the proposed framework.
RESULTS: Burnout was negatively related to self-efficacy and outcome
expectations. Self-efficacy was positively related to outcome expectations.
Outcome expectations were also positively related to career interest. However,
self-efficacy was not related to career interest. Career interest was negatively
related to the intention to leave the organization, which was further related to
the intention to leave the profession. The model fitted the data acceptably.
CONCLUSIONS: When nurses leave the profession, patient outcomes may be affected.
Policy makers should evaluate whether the healthcare system can instil
expectations for satisfaction, power and adequate compensation in the profession
and thus retain nurses.
PMID- 29943841
TI - MicroRNA-198 inhibition of HGF/c-MET signaling pathway overcomes resistance to
radiotherapy and induces apoptosis in human non-small-cell lung cancer.
AB - Non-small-cell lung cancer (NSCLC) is the most common cause of death from cancer
worldwide. MicroRNAs (miRNAs) are a group of important regulators in NSCLC,
including miR-198. However, the underlying molecular mechanisms of miR-198
involvement in intrinsic resistance to radiotherapy in NSCLC remain to be
elucidated. In this study, to investigate the clinical significance of miR-198 in
NSCLC in relation to the response to radiotherapy, we determined the expression
patterns of miR-198 between responders and nonresponders after 2 months of
radiotherapy and found that decreased expressions of miR-198 were associated with
radiotherapy resistance. In addition, we altered the endogenous miR-198 using
mimics or inhibitors to examine the effects of miR-198 on 4-Gy-irradiated A549
and SPCA-1 cells in vitro. Upregulating miR-198 was shown to inhibit cell
proliferation, migration, and invasion and induce apoptosis. MiR-198 inhibition
produced a reciprocal result. PHA665752, a selective small-molecule c-Met
inhibitor, potently inhibited hepatocyte growth factor (HGF)-stimulated and
constitutive c-Met phosphorylation and rescued 4-Gy-irradiated A549 and SPCA-1
cells from miR-198 inhibition. Most importantly, we established tumor xenografts
of 4-Gy-irradiated A549 and SPCA-1 cells in nude mice and found that miR-198
could suppress tumor formation. Hence, our data delineates the molecular pathway
by which miR-198 inhibits NSCLC cellular proliferation and induces apoptosis
following radiotherapy, providing a novel target aimed at improving the
radiotherapeutic response in NSCLC.
PMID- 29943842
TI - Leishmania donovani infection differentially regulates small G-proteins.
AB - Leishmania is a protozoan parasite that resides and replicates in macrophages and
causes leishmaniasis. The parasite alters the signaling cascade in host
macrophages and evades the host machinery. Small G-proteins are GTPases, grouped
in 5 different families that play a crucial role in the regulation of cell
proliferation, cell survival, apoptosis, intracellular trafficking, and
transport. In particular, the Ras family of small G-proteins has been identified
to play a significant role in the cellular functions mentioned before. Here, we
studied the differential expression of the most important small G-proteins during
Leishmania infection. We found major changes in the expression of different
isoforms of Ras, mainly in N-Ras. We observed that Leishmania donovani infection
led to enhanced N-Ras expression, whereas it inhibited K-Ras and H-Ras
expression. Furthermore, an active N-Ras pull-down assay showed enhanced N-Ras
activity. L donovani infection also increased extracellular signal-regulated
kinase 1/2 phosphorylation and simultaneously decreased p38 phosphorylation. In
contrast, pharmacological inhibition of Ras led to reduction in the
phosphorylation of extracellular signal-regulated kinase 1/2 and enhanced the
phosphorylation of p38 in Leishmania-infected cells, which could lead to
increased interleukin-12 expression and decreased interleukin-10 expression.
Indeed, farnesylthiosalicyclic acid (a Ras inhibitor), when used at the effective
level in L donovani-infected macrophages, reduced amastigotes in the host
macrophages. Thus, upregulated N-Ras expression during L donovani infection could
be a novel immune evasion strategy of Leishmania and would be a potential target
for antileishmanial immunotherapy.
PMID- 29943843
TI - Generation of tolerogenic dendritic cells using Lactobacillus rhamnosus and
Lactobacillus delbrueckii as tolerogenic probiotics.
AB - Systemic lupus erythematosus (SLE) concurs with excessive uncontrolled
inflammatory immune responses that lead to the loss of immune tolerance.
Dendritic cells (DCs) are important and determinant immune cells that regulate
immune responses. Tolerogenic DCs with regulatory markers and cytokines could
induce regulatory immune cells and responses. Tolerogenic probiotics are capable
of producing regulatory DCs from monocytes in in vitro conditions. The purpose of
this study was to evaluate the effect of Lactobacillus delbrueckii and
Lactobacillus rhamnosus on the production of DCs in an in vitro condition.
Peripheral blood mononuclear cells were isolated from the healthy and SLE donors.
Monocytes were cultured with optimized concentrations of granulocyte-macrophage
colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to produce immature
DCs (IDCs). An IDC uptake assay was performed, and IDCs of healthy and SLE donors
were divided into three subgroups following 48 hours of treatment with GM-CSF and
IL-4, along with L. delbrueckii, L. rhamnosus, and mixed probiotics for the
production of tolerogenic DCs. The surface expression of Human Leukocyte Antigen
antigen D Related (HLA-DR), CD86, CD80, CD83, CD1a, and CD14 was analyzed using
flow cytometry, and the gene expression levels of indoleamine 2,3-dioxygenase
(IDO), IL-10, and IL-12 were measured using real-time polymerase chain reaction.
We observed significantly reduced expression of costimulatory molecules and other
surface markers in the probiotic-induced mature DCs (MDCs) in both healthy and
SLE donor groups in comparison with lipopolysaccharide (LPS)-induced MDCs. In
addition, the expression of IDO and IL-10 increased, whereas IL-12 decreased
significantly in probiotic-induced MDCs compared with LPS-induced MDCs. IDCs and
especially mature tolerogenic DC of SLE patients highly expressed IDO. The
results of the current study suggested that live probiotics could modify
properties of DCs to modulatory cells, which might contribute to the induction of
tolerance and renovation of immune hemostasis.
PMID- 29943844
TI - The value of measurement for development of nursing knowledge: Underlying
philosophy, contributions and critiques.
AB - AIM: A philosophical discussion of constructive realism and measurement in the
development of nursing knowledge is presented. BACKGROUND: Through Carper's four
patterns of knowing, nurses come to know a person holistically. However,
measurement as a source for nursing knowledge has been criticized for underlying
positivism and reductionist approach to exploring reality. Which seems mal
alignment with person-centred care. DESIGN: Discussion paper. DISCUSSION:
Constructive realism bridges positivism and constructivism, facilitating the
measurement of physical and psychological phenomena. Reduction of complex
phenomena and theoretical constructs into measurable properties is essential to
building nursing's empiric knowledge and facilitates (rather than inhibits)
person-knowing. IMPLICATIONS FOR NURSING: Nurses should consider constructive
realism as a philosophy to underpin their practice. This philosophy supports
measurement as a primary method of inquiry in nursing research and clinical
practice. Nurses can carefully select, and purposefully integrate, measurement
tools with other methods of inquiry (such as qualitative research methods) to
demonstrate the usefulness of nursing interventions and highlight nursing as a
science.
PMID- 29943845
TI - A novel molecular mechanism of microRNA-21 inducing pulmonary fibrosis and human
pulmonary fibroblast extracellular matrix through transforming growth factor
beta1-mediated SMADs activation.
AB - Pulmonary fibrosis (PF), characterized by the destruction of lung tissue
architecture and the abnormal deposition of extracellular matrix (ECM) proteins,
currently has no satisfactory treatment. The role of microRNA (miR)-21 in PF has
been reported; the current study attempted to investigate a novel molecular
mechanism by which miR-21 exerted its function. Consistent with previous studies,
miR-21 inhibition reduced ECM protein levels in bleomycin (BLM)-induced mouse
model of PF. In human pulmonary fibroblast (IMR-90), miR-21 inhibition reduced
transforming growth factor beta1 (TGFbeta1)-induced ECM protein expression.
Regarding a novel molecular mechanism, TGFbeta1 combined with TGFbeta1 receptor 1
(TGFbeta1RI) to activate SMAD2/3, promote SMAD4 nucleus transformation, and thus
regulate miR-21 expression and ECM. SMAD3 and SMADs complex could bind to the
promoter region of miR-21 to promote miR-21 expression. In conclusion, miR-21
exerts promotive effects on BLM-induced PF and TGFbeta1-induced ECM in IMR-90;
TGFbeta1 combines with TGFbeta1RI to activate SMAD2/3, promote SMAD4 nucleus
transformation, promote miR-21 expression, and thus to promote BLM-induced PF and
TGFbeta1-induced ECM in IMR-90 cells.
PMID- 29943847
TI - Pathological cyclic strain promotes proliferation of vascular smooth muscle cells
via the ACTH/ERK/STAT3 pathway.
AB - Abnormal proliferation of vascular smooth muscle cells (VSMCs) is closely related
to hyperplasia in hypertension. Our previous study suggested that
adrenocorticotropic hormone (ACTH) is mechano-responsive and may regulate VSMC
proliferation. However, the molecular mechanism of VSMC abnormal proliferation
induced by conditions of high cyclic strain, especially the role of ACTH in this
process, is unclear. Our results revealed that ACTH and its specific receptor
melanocortin receptor type 2 (MC2R) were highly expressed in hypertensive rat
models. Furthermore, it was demonstrated that the expression of ACTH and MC2R was
up-regulated when exposed to high cyclic strain in vitro, accompanied by abnormal
proliferation of VSMCs. Next, it was proved that ACTH-dependent cell
proliferation was related to the phosphorylation of extracellular regulated
protein kinases (ERK) and signal transducer and activator of transcription 3
(STAT3). The study also found that ACTH could promote dimerization and
glycosylation of melanocortin 2 receptor accessory protein (MRAP), which had a
significant effect on MC2R membrane localization and signal activation. When
VSMCs were treated with PD98059, a mitogen-activated protein kinase (MAP kinase)
cascade antagonist, it was determined that phosphorylation of STAT3 at Ser727 was
dependent on ERK phosphorylation. In summary, these data demonstrated that the
abnormal proliferation of VSMCs induced by conditions of high cyclic strain is in
part attributed to ACTH and its receptor MC2R. Identifying the mechanism of ACTH
dependent proliferation of VSMCs may help to provide new therapeutic targets for
hypertension.
PMID- 29943846
TI - Pleural adverse drugs reactions and protein kinase inhibitors: Identification of
suspicious targets by disproportionality analysis from VigiBase.
AB - AIMS: To evaluate the risk of pleural disorders (PD) associated with 33 protein
kinase (PK) inhibitors (PKIs) through a disproportionality analysis and to
identify which PKs and pathways are involved in PKI-induced PD. METHODS: To
evaluate the risk of PD, reporting odds ratios (RORs) were calculated for 33 PKIs
through data registered in the World Health Organization safety report database
(VigiBase). We undertook a literature review to identify PKs that were possibly
involved in PD caused by PKIs. Pearson correlation coefficients (r) between RORs
and affinity data of 19 PKIs were calculated to identify the cellular target most
likely to be involved in PKI-induced PD. RESULTS: A total of 235 110 individual
case safety reports were extracted from the database for 33 available PKIs. Among
these reports, 5001 concerned PD (2.1%). Significant and positive
disproportionality for PD was found for 29 of 33 PKI included in our study with
top values for dasatinib [ROR = 115.3; 95% confidence interval (CI): 110.1
120.8], bosutinib (ROR = 20.4; 95% CI: 15.8-26.4) and ponatinib (ROR = 12; 95%
CI: 9.2-15.6). Correlation analyses between the product of dissociation constant
and ROR highlighted possibly Lyn involvement in PD with PKI (r = 0.73, P =
0.0004). CONCLUSIONS: Our study showed that 28 of the 33 tested PKIs were
associated with PD. Besides, the study highlighted the role of Lyn in PD caused
by PKIs through an immune-mediated process.
PMID- 29943848
TI - Dermatoscopic features of lichen nitidus.
AB - Dermatoscopy is a noninvasive, painless, and easily repeatable technique that
reveals interesting and characteristic features associated with various cutaneous
conditions. Lichen nitidus is a rare dermatosis of childhood. We describe the
dermatoscopic features in 8 cases of lichen nitidus, which can aid noninvasive
diagnosis. The report serves to emphasize the need for examining these lesions
using both polarized and nonpolarized modes.
PMID- 29943849
TI - Prescription patterns of angiotensin-converting enzyme inhibitors for various
indications: A UK population-based study.
AB - AIM: Angiotensin-converting enzyme inhibitors (ACEIs) are widely prescribed for
several cardiovascular indications. This study investigated patterns of ACEI use
for various indications. METHODS: A descriptive, retrospective population-based
study was conducted using data from the UK Clinical Practice Research Datalink.
Patients starting ACEIs (2007-2014) were selected and ACEI indications were
retrieved from electronically recorded medical records. Stratified by indication,
we distinguished between persistent and nonpersistent ACEI use, considering a 6
month interval between two prescription periods as a maximum for persistent use.
Five-year persistence rates for various indications were calculated using the
Kaplan-Meier method and compared in a log-rank test. Nonpersistent users were
subdivided into three groups: (i) stop; (ii) restart; and (iii) switch to an
angiotensin II-receptor blocker. Patients who received ACEIs for hypertension who
switched to other classes of antihypertensive medications were further
investigated. RESULTS: In total, 254 002 ACEI initiators were identified with
hypertension (57.6%), myocardial infarction (MI; 4.2%), renal disease (RD; 3.7%),
heart failure (HF; 1.5%), combinations of the above (17.2%) or none of the above
(15.8%). Five-year persistence rates ranged from 43.2% (RD) to 68.2% (MI; P <
0.0001). RD and HF patients used ACEIs for the shortest time (average 23.6 and
25.0 months, respectively). For the nonpersistent group, the percentage of
switchers to angiotensin II-receptor blockers ranged from 27.6% (RD) to 42.2%
(MI) and the restarters ranged from 15.0% (HF) to 18.1% (group without
indication). CONCLUSIONS: Depending on the indication, there are various rates of
ACEI nonpersistence. Patients with RD are most likely to discontinue treatment.
PMID- 29943850
TI - Enhancing developmental rate and quality of mouse single blastomeres into
blastocysts using a microplatform.
AB - The present work reports the beneficial effects of using a microplatform on the
development of mouse single blastomeres (SBs) to the blastocyst stage.
Development of blastocysts from SBs separated from two- and four-cell stage
embryos (two- and four-cell SBs) can provide a valuable supply both for couples
who use fertility-assisted techniques and farm animals. As a step forward, we
introduce three chips that provide the possibility of culturing SBs separately,
in groups, and in the vicinity of the intact embryo (co-culture), while each well
of the chips is assigned to an isolated SB. Two- and four-cell SBs co-cultured
with intact embryos showed 97.1% and 76.6% developmental rates and up to 34.1%
and 49.1% growth relative to the microdroplet method (control). We examined the
quality of developed blastocysts by assessing the total cell number, the number
of inner cell mass (ICM) according to the octamer-binding transcription factor 4
marker (OCT4), and trophectoderm (TE). Co-culture of SBs with an intact embryo in
a chip with nanoscale culture medium volume also increased the cell population of
the developed embryo. The ICM:TE ratio, which is the most important blastocyst
quality parameter, also indicated that developed two-cell SBs have a higher
degree of similarity to intact embryos despite fewer numbers of total cells.
PMID- 29943851
TI - Pediatric "pet consort dermatitis"-Allergic contact dermatitis from transfer of
bronopol from a pet cat.
AB - Consort dermatitis refers to an allergic contact dermatitis caused by transfer
from an intimate contact to a sensitized patient. Although close contact with
other humans most commonly provokes consort dermatitis, pets have been the source
in a minority of cases. We present a unique case of transfer dermatitis from a
patient's cat litter to her forearms. Pediatric dermatologists should be aware of
the possibility of consort or "transfer" allergic contact dermatitis from pets.
PMID- 29943852
TI - Methotrexate for severe nummular eczema in children: Efficacy and tolerability in
a retrospective study of 28 patients.
AB - BACKGROUND/OBJECTIVES: Nummular eczema in children is a chronic condition
characterized by pruritic coin-shaped eczematous lesions that affect any part of
the body and often become exudative. Mid- to high-potency topical corticosteroids
are considered the mainstay treatment, but there are limited data on the use of
systemic therapy for nummular eczema in children. The objective of the current
study was to evaluate the efficacy and safety of methotrexate in children with
severe nummular eczema. METHODS: A retrospective review was undertaken of
children with nummular eczema treated with methotrexate between January 2007 and
May 2017. RESULTS: The records of 28 patients (24 male, 4 female) with a mean age
at the beginning of treatment of 7.8 +/- 1.6 years (95% confidence interval (CI)
= 6.1-9.4 years) were reviewed. The median duration of treatment was 12.6 +/- 3.3
months (95% CI = 9.2-16 months), and 14 patients were still undergoing
methotrexate therapy at the time of last review. Ten patients (35.7%) had
complete or almost complete clearance of eczema (> 90% improvement), 13 (46.4%)
had marked improvement (50%-89%), four had mild improvement (< 50%), and one
failed methotrexate therapy. Gastrointestinal intolerance (21.4%) and a
nonsignificant increase in liver enzymes (17.9%) were the most frequent side
effects. No serious adverse events were noted. CONCLUSION: Methotrexate is an
effective, well-tolerated treatment in children with moderate to severe nummular
eczema that has failed to respond to conventional topical therapy.
PMID- 29943853
TI - Successful thrombolysis of a subacute prosthetic valve thrombosis with modified
ultra-slow thrombolytic therapy.
AB - Prosthetic valve thrombosis is a serious complication of heart valve surgery.
According to the recent studies, thrombolytic therapy is an important alternative
therapy to the open heart surgery with successful outcomes. We present a case of
a prosthetic mitral valve thrombosis who was successfully treated with modified
ultra-slow thrombolytic therapy.
PMID- 29943854
TI - Interindividual differences in the clinical effectiveness of liraglutide in Type
2 diabetes: a real-world retrospective study conducted in Spain.
AB - AIMS: To study the response of clinical variables (HbA1c , body weight, lipid
profile and blood pressure) over 24 months of liraglutide treatment in a real
world clinical setting, and to describe the evolution of HbA1c and body weight
reduction in response to liraglutide treatment by employing generalized additive
mixed models (GAMMs). METHODS: We included people aged >= 18 years with Type 2
diabetes mellitus that initiated liraglutide treatment between November 2011 and
May 2015. Demographic and clinical data were retrieved retrospectively over 24
months from electronic medical records with a median duration of observation of
7.0 (IQR 3.0-12.0) months. RESULTS: Individuals that initiated liraglutide
therapy were obese (BMI 39.1 kg/m2 ), with inadequate HbA1c (68 mmol/mol [8.4%]),
blood pressure and lipid levels. Upon liraglutide treatment, HbA1c , body weight,
mean systolic and diastolic blood pressure, and lipid levels decreased gradually.
GAMMs demonstrated that longer treatment with liraglutide was a predictor of
improved HbA1c response, whereas higher baseline HbA1c , longer Type 2 diabetes
duration and treatment with insulin were predictors of worse HbA1c response.
Higher baseline weight, longer treatment with liraglutide and the interaction
between metformin and time were predictors of improved weight response.
CONCLUSIONS: In this real-world study, we showed the effectiveness of liraglutide
in improving body weight, HbA1c , mean systolic and diastolic blood pressure, and
lipid levels. GAMMs indicated that baseline HbA1c and weight, time of treatment
with liraglutide, diabetes duration and the use of metformin or insulin are
predictors of clinical response to liraglutide.
PMID- 29943855
TI - Multiple Spitz nevi after allogeneic hematopoietic stem cell transplantation.
AB - Spitz nevus commonly appears as a solitary lesion. A 12-year-old male patient
presented with a 6-month history of several pigmented lesions on his trunk and
lower extremities. He had undergone chemoradiotherapy and unrelated umbilical
cord blood transplantation against recurring acute lymphoblastic leukemia for 6
years. After that, several pigmented lesions abruptly developed on his trunk and
lower extremities, and the number of those increased significantly.
Pathologically, the diagnosis of multiple Spitz nevi was made. In a clinical
correlation, we diagnosed multiple Spitz nevi resulting from such an
immunocompromised condition. This is the first description of clinical,
dermoscopic, and histopathologic features of multiple Spitz nevi in the
hematopoietic cell transplantation (HSCT) recipient child.
PMID- 29943856
TI - Left atrial function: Correlation with left ventricular function and contractile
reserve in patients with hypertension.
AB - AIMS: Alterations in left atrial (LA) and left ventricular (LV) function have
been documented in hypertensive patients. However, the correlation of LA with LV
functional changes has not been established. Using normotensive controls, we
examined LA functional changes in hypertensive patients by strain deformation
analysis, and their relationship to LV functional changes including contractile
reserve (CR). METHODS: One hundred and sixteen patients (61 men, aged 57.6 +/-
9.1 years, 67 with hypertension) underwent dobutamine echocardiography. Patients
with significant coronary or valvular disease, previous myocardial infarction or
coronary revascularization, and diabetes were excluded. LA reservoir (Es),
conduit (Ee), and atrial contractile (Ea) strain were measured at rest. LV global
longitudinal strain (GLS) and ejection fraction (LVEF) were measured at rest and
at low-dose dobutamine. LV CR was calculated as the difference in GLS and LVEF
between the low dose and their corresponding resting values. RESULTS:
Hypertensive patients, compared with controls, had significantly impaired LA Es
(30.7 +/- 3.9% vs 42.4 +/- 4.9%), Ee (16.2 +/- 4.1% vs 22.5 +/- 5.5%), and Ea
(14.5 +/- 4.1% vs 19.9 +/- 5.0%, all P < .001) strain. All LA phasic strain
correlated with LV GLS at rest, at low-dose dobutamine, and LV CR. There was no
correlation between LA strain and LVEF or LV CR assessed by LVEF. LV GLS and
LAVImax were the strongest independent determinants for LA Es/Ee and LA Ea,
respectively. CONCLUSION: Compared to controls, hypertensive patients had
impaired LA strain, which correlated with LV GLS and CR. LV GLS and LAVImax were
the strongest independent determinants for LA Es/Ee and LA Ea, respectively,
independent of BP and LVMi.
PMID- 29943858
TI - Occurrence of oral health problems and planned measures in dependent older people
in nursing care.
AB - AIMS AND OBJECTIVE: To describe oral health problems and planned measures in
older people receiving nursing care. BACKGROUND: Poor oral health conditions have
a negative impact on the quality of life of older people. Therefore, oral care is
an important task in daily nursing activities. METHODS: Data were obtained from
the web-based Swedish national quality register Senior Alert. Data regarding oral
health status and planned measures in individuals >=65 years from one county in
Sweden between July 2014-June 2015 were included. The Revised Oral Assessment
Guide-the Jonkoping (ROAG-J) was used routinely by nursing staff in nursing care
facilities to measure oral health status. RESULTS: Oral assessments were made on
2,567 individuals (65.7% women). The most common oral health problem was related
to "Teeth" (43.0%), which indicates deficient oral hygiene and/or broken teeth.
At least one measure was planned in all the participants. The most common planned
measures were "Moistening of the mouth" (16.6%), followed by "Brushing -
assistance or complete help" (13.5%). CONCLUSION: Oral health problems were
common, and planned measures did not seem to be sufficient to address the
identified problems. The results indicate that greater priority should be given
to the oral health care of older people in nursing care. RELEVANCE TO CLINICAL
PRACTICE: The study highlights the importance of not only identifying oral health
problems but also having knowledge and strategies for oral health care.
Collaboration is needed to support nurses in caring for the oral health care of
older people in nursing homes.
PMID- 29943857
TI - Fetal modified left myocardial performance index monitoring during open surgery
for myelomeningocele repair.
AB - OBJECTIVE: Fetal hemodynamic changes have already been described during open
myelomeningocele repair. This study aimed to access fetal myocardial performance
index (MPI) during this high-complexity surgery. METHODS: Open myelomeningocele
repair was performed in 37 fetuses between the 24th and 27th week of gestation.
MPI was calculated at specific periods: pre-anesthesia, postanesthesia,
neurosurgery (early skin manipulation, spinal cord releasing, and sintesis), and
end of surgery. Mean +/- standard deviation (SD) of MPI and its related times
isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and
ejection time (ET)-was determined for each period. Analysis of variance (ANOVA)
with repeated measures was used to assess differences among these periods. Tukey
multiple comparison times test compared global surgery stages. RESULTS: The mean
of MPI in the specific time points was 0.32, 0.32, 0.34, 0.48, 0.36, and 0.32,
respectively (P < .001). In the two-tailed comparison times, neurosurgery stage
presents MPI highest levels, especially on stage 3b (early skin manipulation and
spinal cord releasing) related to ICT and IRT rising and ET decreased levels.
CONCLUSION: Fetal global cardiac function is altered during the open
myelomeningocele repair. The neurosurgery stage represents the critical phase of
the procedure.
PMID- 29943859
TI - Cutaneous manifestations in Egyptian children with beta-thalassemia major:
Relationship with serum ferritin, thyroid profile, and treatment modalities.
AB - BACKGROUND: Cutaneous manifestations can be found in many patients with
hematologic disorders, including thalassemia. METHODS: Patients with beta
thalassemia major attending the pediatric department of Fayoum University
Hospital from April 2016 to October 2016 (n = 100) were compared with controls (n
= 100). Both groups underwent detailed history evaluation, clinical examination,
and laboratory investigations, including complete blood count, liver and kidney
function, serum ferritin, and thyroid profile. A single dermatologist conducted a
clinical dermatologic examination for all participants. RESULTS: Children with
thalassemia had a greater prevalence of xerosis (72%), pruritus (52%), idiopathic
guttate hypomelanosis (22%), urticaria (16%), ephelides (freckles; 13%), and
scars (13%) than controls (P <= .001). We detected a significant relationship
between serum ferritin and pruritus, xerosis, ephelides, idiopathic guttate
hypomelanosis, urticaria, and age of patients with thalassemia (P < .05).
Children without thyroid abnormalities were more likely to have xerosis,
pruritus, idiopathic guttate hypomelanosis, urticaria, and ephelides (86%) than
controls (P < .05). Although there was no significant difference in skin findings
between patients who did and did not receive chelating agents (P > .05), a
significant association was found between xerosis and the use of deferoxamine and
deferiprone, whereas ephelides and urticaria were more common in patients
receiving deferasirox. CONCLUSION: Because cutaneous manifestations are common in
Egyptian patients with beta thalassemia major, regular dermatologic follow-up is
recommended for early management.
PMID- 29943860
TI - Altered susceptibility to air sampling stress by filtration is related to
colistin resistance development in Acinetobacter baumannii.
AB - The accurate quantification of antibiotic-resistant bacteria in indoor air has
recently attracted increasing attention. Here, we investigated whether the
susceptibility of a nosocomial infection-related microbe, Acinetobacter
baumannii, to strong sampling stress caused by Nuclepore filter changes as it
develops resistance to a drug called colistin. Both colistin-sensitive A.
baumannii (CSAB) and colistin-resistant A. baumannii (CRAB) are generally
desiccation-resistant strains that can be collected by filter sampling. However,
the resistance of CRAB to the three combined stresses (aerosolization, impaction,
and desiccation) caused by filter sampling was 1.8 times lower than that of CSAB
(P < 0.05). The sampling stresses caused by filter sampling not only reduced the
culturability of A. baumannii but also destroyed proteins to result in cellular
protein leakage. CRAB released 17%-38% more extracellular protein than did CSAB
when they were both subjected to desiccation stress for 240 minutes (P < 0.01).
The combination of using a sampling flow rate of 20 L/min and sampling for 60
minutes with a Nuclepore filter with open-face cassettes (OFCs) is recommended
for collecting airborne A. baumannii. A Nuclepore filter operated with closed
face cassettes (CFCs) significantly decreased the culturability of CRAB due to
desiccation effects.
PMID- 29943861
TI - Level of knowledge, emotional impact and perception about the role of nursing
professionals concerning palliative sedation.
AB - AIMS AND OBJECTIVES: To explore aspects related to the fulfilment of the role of
nurses in palliative sedation. BACKGROUND: Palliative sedation demands knowledge
and a proper attitude for maintaining comfort, preserving dignity and
contributing to a peaceful death. In some developed countries, nurses have a well
established role in palliative sedation. However, studies on their role and its
fulfilment are limited, particularly in the developing world. DESIGN: An
exploratory, mixed, qualitative and quantitative study was conducted. A self
administered questionnaire was used to examine the level of knowledge of
palliative sedation and the level of confidence in skills and knowledge about
palliative sedation. Also, focus groups were conducted to explore the emotional
impact and the perceived role of nurses. METHODS: Forty-one nurses from three
advanced-care hospitals with palliative care units in Colombia completed the
questionnaire. Also, four focus groups were conducted with 22 participants
selected from the first phase. RESULTS: A high level of knowledge regarding
palliative sedation was found, but the level of confidence in skills was higher
than the confidence in knowledge. The participants expressed their belief that
their knowledge was derived from experience but believed that it was not enough
to fulfil their role with confidence. A negative emotional impact about the
patients' condition was found. For some, it served as motivation to provide
better care. For others, it was difficult to face, especially when assisting
children. They also expressed satisfaction and gratification about providing
relief from suffering through sedation. CONCLUSIONS: The role of nursing is
essential in palliative sedation. Although the nurses' knowledge is adequate, it
primarily derives from experience and not from formal training, which impacts on
their perceived confidence and their distress. RELEVANCE TO CLINICAL PRACTICE:
Formal training for the optimal fulfilling of the nursing role in palliative
sedation is crucial to provide better end-of-life care, particularly in
developing countries.
PMID- 29943862
TI - Meta-analysis of the effects of rice-field abandonment on biodiversity in Japan.
AB - Farmland abandonment is increasing worldwide. Concurrently, some conservationists
view this as an opportunity for biodiversity restoration (i.e., rewilding). Due
to a lack of data, however, it remains unclear whether farmland abandonment
increases biodiversity in different farmland types and surrounding environments.
Information is particularly scarce for Asia, home to one-third of identified
biodiversity hotspots and where dominant farmlands (i.e., rice fields) are often
viewed as substitutes for natural wetlands. We conducted the first meta-analysis
of the impacts of rice-field abandonment on biodiversity, in which we considered
multiscale factors, such as taxon surveyed, landscape context, and climate.
Species richness and abundance after abandonment decreased to 56-72%. This
reduced biodiversity was unlikely to recover, at least for plant species
richness, even after 10-15 years. These results suggest rewilding will not
necessarily be achieved by rice-field abandonment. Moreover, there was a
pronounced biodiversity decline under dry conditions (e.g., low precipitation),
especially for organisms closely associated with aquatic environment, such as
amphibians and fish. Biodiversity reduction was least pronounced for birds and
mammals. Such context dependency may suggest that impacts of farmland abandonment
can be predicted by considering biological features of organisms and their
associations with human-modified environments.
PMID- 29943863
TI - The price of journeying towards the prize-Commencing nursing students'
experiences of working and studying: A qualitative study.
AB - AIMS AND OBJECTIVES: To explore the experiences of commencing first-year
undergraduate nursing students who were studying full time while engaging in 20
or more hours of paid work each week. METHOD: Using a qualitative exploratory
design, commencing full-time nursing students who were employed in paid work for
at least 20 hr per week were interviewed between May-June 2016. Data were
thematically analysed using the following approach: data familiarisation,
generating initial codes independently, searching and reviewing themes and
subthemes, and defining and naming these themes and subthemes. RESULTS: Four main
themes were identified which illustrated students' experiences of working and
studying: (a) "Work is a necessity...not a choice" identified how students relied
heavily on the financial income from paid work to support themselves and others
during their studies, (b) "Something's got to give" highlighted the sacrifices
that needed to be made to avoid negative effects on their studies, (c) "It's a
balancing act!" demonstrated how students studied strategically and balanced
their workload despite challenges, and lastly (d) "Being supported to work and
study" described the overwhelming support from others for students to succeed
academically. CONCLUSIONS: Despite support, working 20 hr or more per week while
studying full time often overwhelmed students' personal resources and negatively
impacted on course grades. Inflexible University timetables compounded the
challenges experienced by students who struggled to balance work and study
commitments. RELEVANCE TO CLINICAL PRACTICE: Nursing employers play a pivotal
role in enabling students to juggle effectively their work-study commitments,
through providing work flexibility. Students may also benefit if the nursing
workforce advocates that they be awarded exclusion from selected clinical
placement requirements, particularly if the clinical placement focus is closely
related to their current nursing employment.
PMID- 29943864
TI - Lewis Superacids: Classifications, Candidates, and Applications.
AB - Lewis acids play a major role in all areas of chemistry. For a long time, toxic,
corrosive and oxidizing SbF5 was considered as the strongest Lewis acid known.
Lately, species significantly exceeding the Lewis acidity of SbF5 have been
realized and were termed Lewis superacids (LSA). Prospective new candidates
emerge steadily, which not only outperform SbF5 by their strength, but also in
terms of their accessibility and ease of handling. In principle, Lewis superacids
allow us to combine the outstanding activity of Bronsted superacids with the
excellent selectivity of a common Lewis acid. However, the broad application of
Lewis superacids in synthesis is all but popular. The present review deals with
strong Lewis acids. First, it critically discusses Lewis acidity scaling methods
and suggests an extended definition for Lewis superacidity. It then summarizes
the properties and applications of the strongest currently known Lewis acids,
indexed by the fluoride ion affinity (FIA). The supporting information contains a
comprehensive list of experimentally and theoretically derived FIA data as a
guide for the choice of Lewis acidic reagents/catalyst. This contribution shall
encourage the search for new Lewis superacids and promote their application in
non-specialized laboratories.
PMID- 29943865
TI - Mass spectrometric characterization of intact desferal-conjugated monoclonal
antibodies for immuno-PET imaging.
AB - RATIONALE: Immuno-PET imaging may prove to be a diagnostic and
progression/intervention biomarker for Alzheimer's disease (AD) with improved
sensitivity and specificity. Immuno-PET imaging is based on the coupling of an
antibody with a chelator that captures a radioisotope thus serving as an in-vivo
PET ligand. A robust and quality controlled process for linking the chelator to
the-antibody is fundamental for the success of this approach. METHODS: The
structural integrities of two monoclonal antibodies (trastuzumab and
JRF/AbetaN/25) and the quantity of desferal-based chelator attached following
modification of the antibodies were assessed by online desalting and intact mass
analysis. Enzymatic steps for the deglycosylation and removal of C-terminal
lysine was performed sequentially and in a single tube to improve intact mass
data. RESULTS: Intact mass analysis demonstrated that inclusion of enzymatic
processing was critical to correctly derive the quantity of chelator linked to
the monoclonal antibodies. For trastuzumab, enzymatic cleaving of the glycans was
sufficient, whilst additional removal of the C-terminal lysine was necessary for
JRF/AbetaN/25 to ensure reproducible assessment of the relatively low amount of
attached chelator. CONCLUSIONS: An efficient intact mass analysis-based process
was developed to reproducibly determine the integrity of monoclonal antibodies
and the quantity of attached chelator. This technique could serve as an essential
quality control approach for the development and production of immuno-PET
tracers.
PMID- 29943866
TI - Able to purchase? Agency problems in China's social health insurance system and
the pitfalls of third-party strategic purchasing.
AB - The notion of strategic purchasing has gained increasing currency in the global
health policy discourse. It is believed that an active prudent purchaser is able
to act in the best interest of both government and consumers as a third party
negotiating with providers for cost-effective care. It would be wrong, however,
to assume that the formation of a third-party purchaser automatically leads to
such desired outcomes. A variety of agency problems relating to incompetence
often prevent purchasers from fulfilling their mandates, aggravating cost
inflation. This study provides an alternative explanation for the rapid cost
inflation in the Chinese health system, by focusing on the unique role played by
the social health insurance administration. Provincial-level panel data analysis
reveals that misaligned bureaucratic incentives and limited administrative
capacity of the social health insurance administration contribute significantly
to rapidly escalating costs. This study argues that despite the merit of the
notion of third-party strategic purchasing, it must not be forgotten that
effective purchasing hinges on certain crucial prerequisites that may not
necessarily be present in reality. Appropriate alignment of the social health
insurance administration's organizational mandates and development of its
capacity is essential to China's move towards strategic purchasing of health
services.
PMID- 29943867
TI - Short-term longitudinal changes in adult dental fear.
AB - This study aimed to evaluate (i) longitudinal fluctuations and considerable
changes in adult fear at five data-collection points during a 2.5-yr period and
(ii) the stability of symptoms of depression in dental fear-change groups. Pilot
data from the FinnBrain Birth Cohort study, of 254 families expecting a baby,
were used. Data-collection points (DCPs) were: 18-20 and 32-34 gestational weeks;
and 3, 12, and 24 months after delivery. At baseline, 119 women and 85 men
completed the Modified Dental Anxiety Scale (MDAS) questionnaire. At all DCPs, 57
(48%) women and 35 (41%) men completed MDAS. Depression was measured using the
Edinburgh Postnatal Depression Scale. Changes in MDAS were analyzed using general
linear modelling for repeated measures. Stability of dental fear was assessed
using dichotomized MDAS scores. Dental fear among women decreased statistically
significantly in late pregnancy and increased thereafter. Among men, dental fear
tended to increase in late pregnancy and decreased afterwards. Depression scores
varied in high and fluctuating fear groups but the differences diminished towards
the last DCP. Dental fear among adults experiencing a major life event does not
seem to be stable. Clinicians should take this into account. The mechanisms
behind these changes need further research.
PMID- 29943869
TI - Arthritis in Kawasaki disease: A poorly recognised manifestation.
AB - AIM: To determine the prevalence of arthritis in Kawasaki disease (KD) and the
clinical characteristics of children with KD and arthritis. METHODS: This was a
single-centre, 15-year, retrospective study of children admitted with KD.
Clinical features (including coronary involvement), laboratory results and
treatment response were evaluated. RESULTS: Of 63 children with KD, 60.3% were
male, with a median of age of 2.0 years. Complete KD was found in 68.3%. The time
from symptom onset to treatment was 7.0 days (median); 30.7% had coronary artery
aneurysms, from which 82.5% responded to intravenous immunoglobulin. During the
course of their illness, eight children developed arthritis (12.7%), which was
early onset in six (75%) and oligoarticular in five (62.5%). The median number of
joints was 3.5 (P25 = 1.3, P75 = 17.0), and at least one large joint was
affected. In all cases, the arthritis was self-limited and left no sequelae,
lasting a median of 14 days and no longer than 22 days. KD children with
arthritis were older (P = 0.025), and those with early-onset arthritis responded
to first-line therapy, unlike the late-onset group (P = 0.018). CONCLUSIONS: This
study emphasises the value of a systematic articular examination of joints in KD.
Refractory KD was observed in children with late-onset arthritis.
PMID- 29943870
TI - Beamforming algorithms for endocardial border detection.
AB - BACKGROUND: Software-based beamforming which utilizes delay and standard
beamforming is a signal processing technique that temporarily stores data from
each probe element to improve specular reflections to improve the image
resolution. We compared a software algorithm which uses delay and standard
beamforming with delay and sum beamforming in standard, hardware to evaluate
endocardial borders and need for echo contrast. METHODS: In this prospective
study, eligible participants were >=18 years of age referred clinically for
transthoracic echocardiograms. A limited study consisting of three views (apical
4, apical 3, and apical 2 chamber) was performed with the software-based
beamforming and standard platform. Number and quality of segments visualized were
evaluated using a 17-segment model. Quality of segments was graded as 0 = not
visualized, 1 = incompletely visualized, or 2 = completely visualized. Overall
quality score for each study (0 = poor, 1 = adequate, 2 = good) was reported. The
need for contrast was determined by ASE guidelines. RESULTS: A total of 101
patients (mean age 61 +/- 16 years, males 52%) were enrolled. Mean number of
segments visualized in apical 4- (6.28 vs 5.65, P < .001), apical 3- (6.27 vs
5.54, P < .001), and apical 2-chamber views (6.26 vs 5.72 P < .001) was higher
with the software vs standard platform. The average overall score for image
quality was significantly better for the software platform vs standard (1.4 vs
0.9, P =< .001). With the software platform, 23% were judged as requiring
contrast as compared with 45% for the standard platform (P < .001). CONCLUSIONS:
Delay and standard beamforming in software platform identified more segments with
better image quality when compared to the standard high-end platform, decreasing
the need for contrast usage.
PMID- 29943871
TI - Aetiological spectrum, clinical differentiation and efficacy of polyethylene
glycol over lactulose in children with constipation: Experience of 316 cases.
AB - AIM: To find the aetiological spectrum, clinical features to differentiate
organic from functional constipation (FC) and the efficacy of polyethylene glycol
(PEG) over lactulose in the treatment of childhood constipation. METHODS: From
January 2007 to December 2014, 316 consecutive children (up to 18 years) with
constipation were included in this study. FC was defined as per Rome III
criteria. Standard treatment protocol (disimpaction with PEG followed by
laxatives) was followed in FC. Lactulose was used in the first 4 years of study
and PEG in the last 4 years. Success of therapy was assessed at 3 months.
RESULTS: The median age was 44 (25.00-78.00) months, and 227 (72%) were boys. The
majority, 245 (77.5%), had FC, while Hirschsprung disease was the most common
organic cause (39.4%). On multivariate analysis, delayed passage of meconium,
growth failure, absence of retentive posturing and absent faecal impaction
significantly (P < 0.05) determined an organic aetiology. In FC, successful
outcome at 3 months was achieved equally with PEG and lactulose (81 vs. 76%,
respectively). However, more children in lactulose group had to be switched over
to PEG due to lack of efficacy (P = 0.0002). CONCLUSIONS: FC is the most common
cause of constipation in children. Presence of delayed passage of meconium,
growth failure and absence of retentive posturing and absent faecal impaction
raise the suspicion of an organic cause. Both lactulose and PEG are equally
effective. PEG has an edge over lactulose as the need for switch over was
uncommon.
PMID- 29943868
TI - Electrocardiographic findings in 130 hospitalized neonatal calves with diarrhea
and associated potassium balance disorders.
AB - BACKGROUND: Hyperkalemia in neonatal diarrheic calves can potentially result in
serious cardiac conduction abnormalities and arrhythmias. OBJECTIVES: To document
electrocardiographic (ECG) findings and the sequence of ECG changes that are
associated with increasing plasma potassium concentrations (cK+ ) in a large
population of neonatal diarrheic calves. ANIMALS: One hundred and thirty neonatal
diarrheic calves (age <=21 days). METHODS: Prospective observational study
involving calves admitted to a veterinary teaching hospital. RESULTS:
Hyperkalemic calves (cK+ : 5.8-10.2, blood pH: 6.55-7.47) had significantly (P <
.05) longer QRS durations as well as deeper S wave, higher T wave, and higher ST
segment amplitudes in lead II than calves, which had both venous blood pH and cK+
within the reference range. The first ECG changes in response to an increase in
cK+ were an increase in voltages of P, Ta, S, and T wave amplitudes. Segmented
linear regression indicated that P wave amplitude decreased when cK+ >6.5 mmol/L,
S wave amplitude voltage decreased when cK+ >7.4 mmol/L, QRS duration increased
when cK+ >7.8 mmol/L, J point amplitude increased when cK+ >7.9 mmol/L, and ST
segment angle increased when cK+ >9.1 mmol/L. P wave amplitude was characterized
by a second common break point at cK+ = 8.2 mmol/L, above which value the
amplitude was 0. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperkalemia in neonatal
diarrheic calves is associated with serious cardiac conduction abnormalities. In
addition to increased S and T wave amplitude voltages, alterations of P and Ta
wave amplitudes are early signs of hyperkalemia, which is consistent with the
known sensitivity of atrial myocytes to increased cK+ .
PMID- 29943872
TI - Stretch imposed on active muscle elicits positive adaptations in strain risk
factors and exercise-induced muscle damage.
AB - INTRODUCTION: Stretching highly-contracted plantar flexor muscles (isokinetic
eccentric contractions) results in beneficial adaptations in muscle strain risk
factors; however its effects in other muscle groups, and on architectural
characteristics and exercise-induced muscle damage (EIMD), are unknown. METHODS:
The influence of a 6-week knee extensor training program was studied in 26
volunteers (13 control; 13 experimental). Before and after the training program,
passive and maximal isometric and eccentric knee extensor moments and range of
motion (ROM) were recorded on an isokinetic dynamometer with simultaneous
ultrasound imaging of vastus lateralis (VL). On a separate day, EIMD markers
(creatine kinase [CK], delayed onset muscle soreness [DOMS]) were measured before
and 24 hours after a 20-minute downhill run. The 6-week training program was
performed twice-weekly where five sets of 12 stretches (3 seconds per stretch)
were imposed on maximally contracted knee extensor muscles. RESULTS: Significant
(P < 0.05) increases in eccentric (29.5%) and isometric (17.4%) moments, ROM (5.2
degrees ), stretch tolerance (55.4%), elastic energy storage (73.0%), VL
thickness (7.8%), pennation angle (9.0%), and tendon stiffness (8.7%) occurred.
No change (P > 0.05) in passive muscle-tendon stiffness (-9.4%) or resting
fascicle length (-0.7%) occurred. The downhill run resulted in substantial DOMS
and significant increase in CK concentration before the training program
(107.6%); however, DOMS was eliminated from the knee extensors and a
significantly smaller increase in CK (-70.0%) occurred post-training. CONCLUSION:
Positive adaptations in functional and physiological variables confirm that
imposing stretch on maximally contracted muscle provides beneficial adaptations
likely to mitigate EIMD and injury risk and enhance functional performance.
PMID- 29943873
TI - Usefulness of high-frequency ultrasonography in the assessment of cutaneous
lesions in children with hematologic malignancies.
AB - High-frequency ultrasonography is a bedside tool increasingly used for the
assessment of skin lesions, but there have been few reports about its importance
in children with skin signs of hematologic disease. We present three cases to
highlight the usefulness of high-frequency ultrasonography in assisting with the
diagnosis of these skin lesions.
PMID- 29943874
TI - The last 2 years of life for children with severe physical disability:
Observations from a tertiary paediatric centre.
AB - AIM: To describe the clinical course for children with severe physical disability
(SPD) in the 2 years prior to their death and to identify whether these children
had palliative care involvement and advance care planning prior to death. To
investigate whether there is a difference between children with progressive
(PSPD) and non-progressive (NPSPD) aetiologies of SPD. METHODS: A retrospective
cohort analysis of 48 children with SPD who died between 1 January 2013 and 1
January 2015 at The Royal Children's Hospital, Melbourne. Clinical charts were
reviewed to collect data about the type of SPD, frequency and duration of
hospital admissions, duration of palliative care involvement (if any) and
presence of an advance care plan. RESULTS: The majority of children were admitted
in the 6 months before their death, and over a third were admitted to the
intensive care unit. There was a significant increase in the frequency of
hospital admissions as the study cohort approached death (P = 0.003). The
majority of children with SPD were offered a referral to a palliative care
service, with referrals more likely in children with PSPD (90%) compared to
children with NPSPD (57%). While approximately 60% of children in each cohort had
an advance care plan, there was a trend towards this being formalised earlier in
children with PSPD (P = 0.09). CONCLUSION: The increase in hospital admissions
prior to death in children with SPD suggests an opportunity for greater
consistency in offering advanced care planning and palliative care, especially to
those with NPSPD.
PMID- 29943875
TI - Inflammation-dependent and independent airway remodelling in asthma.
AB - BACKGROUND AND OBJECTIVE: The pathology of asthma is characterized by airway
inflammation (granulocytic (GA) or paucigranulocytic (PGA)) and remodelling of
airway structures. However, the relationship between inflammatory phenotypes and
remodelling is unclear. We hypothesized that some features of airway remodelling
are dependent on granulocytic airway inflammation while others are not. METHODS:
Post-mortem airway sections from control subjects (n = 48) and cases of asthma
with (n = 51) or without (n = 29) granulocytic inflammation in the inner airway
wall were studied. The thickness of the airway smooth muscle (ASM) layer,
basement membrane and inner and outer airway walls, the size and number of ASM
cells, the volume fraction of extracellular matrix within the ASM layer, ASM
shortening and luminal mucus were estimated. Airway dimensions were compared
between the three subject groups. RESULTS: In cases of PGA, only the thickness of
the ASM layer and basement membrane was increased compared with control subjects.
In cases of GA, not only the ASM and basement membrane were increased in
thickness, but there was also increased inner and outer airway wall thickness and
increased narrowing of the airway lumen due to ASM shortening and mucus
obstruction, compared with control subjects. Granulocytic inflammation was
observed more often in cases of fatal asthma. CONCLUSION: These findings suggest
that inner and outer wall thickening coexists with inflammation, whereas
thickening of the ASM layer and basement membrane may be present even in the
absence of inflammation. Remodelling of the ASM layer and basement membrane may
therefore be less susceptible to anti-inflammatory therapy.
PMID- 29943876
TI - Paediatric cardiopulmonary resuscitation: Knowledge and perceptions of surf
lifeguards.
AB - AIM: To conduct a comprehensive analysis of surf lifeguards' real and perceived
ability in paediatric cardiopulmonary resuscitation (CPR), knowledge of child
resuscitation protocols and technical competency during a simulated CPR scenario.
METHODS: Surf lifeguards aged 16 years and over were invited to complete a
written survey and simulated test of five cycles of single-rescuer CPR on a
paediatric manikin. In accordance with the latest Australia and New Zealand
Committee on Resuscitation (ANZCOR) guidelines, practical skills were assessed by
trained observers. A manikin fitted with electronic data-collection capability
recorded technical compression and ventilation skills. RESULTS: A total of 244
participants were entered into the study. Most previous CPR training did not
include a paediatric component (53%). Lifeguards rated their ability to perform
CPR on an adult as 'highly effective' or 'effective' in 56% of responses. Less
than a quarter (23%), however, gave this response when compared to a child.
Observed CPR skills were mostly compliant with ANZCOR guidelines (80-99%).
Manikin data provided a median compression rate of 115.6 min-1 , compression
depth of 3.7 cm and tidal volume of 220.0 mL. Almost half of ventilations were
too little (45%), and around one fifth were too much (22%). CONCLUSIONS: Surf
lifeguards are less confident in paediatric CPR. The overall performance of
observed and technical CPR skills, which were mostly ANZCOR guideline compliant,
suggests that performance could be improved if paediatric-specific training is
provided to supplement the adult-focused methods currently in use. The use of
electronic feedback manikins is recommended to address the technical compression
and ventilation issues identified in this study.
PMID- 29943877
TI - Pyogenic arthritis pyoderma gangrenosum and acne syndrome: A rare but important
diagnosis for antibiotic-resistant erysipelas-like erythema and osteonecrosis.
PMID- 29943878
TI - Prevalence of physical restraint among ventilated intensive care unit patients.
AB - AIMS AND OBJECTIVES: To investigate the prevalence of physical restraint among
mechanically ventilated intensive care unit patients in Jordan and to identify
predicting factors and consequences. BACKGROUND: Physical restraint has been
widely used among intensive care unit patients in many countries. Despite the
benefits it offers in protecting patients from disrupting their medical
treatment, it has been reported that restraint has many physical and
psychological adverse effects. METHOD: A cross-sectional and observational study
was conducted during a period of 3 months (April-June 2017). A sample of 321
intensive care unit patients was selected from five governmental and one
university-affiliated hospital in the north and middle of Jordan. The Restraint
Prevalence Tool was used to collect data from the patients. RESULTS: The study
found that the prevalence of physical restraint use on intensive care unit
patients in Jordan was 35.8%. This prevalence rate varied across the units,
ranging from 33.3%-57.1%. The factors that predicted physical restraint use were
younger age (odds ratio = 0.96), large intensive care unit (odds ratio = 6.14),
the surgical intensive care unit (odds ratio = 10.36), the night shift (odds
ratio = 3.57), a conscious patient (odds ratio = 2.24) and longer hospital stay
(odds ratio = 1.07). However, hospital type, gender and being on chemical
restraint were not significantly associated with physical restraint. Many
patients were observed to have physical complications from restraint use, such as
redness, bruising and oedema. CONCLUSION: Physical restraint is a common practice
in Jordan. Not following standard restraint practices may lead to many physical
complications among intensive care unit patients. RELEVANCE TO CLINICAL PRACTICE:
This study recommends implementing more policies/guidelines inside Jordanian
hospitals. In addition, nursing education programs on the safe use of physical
restraint should be implemented.
PMID- 29943879
TI - Nomenclature in heart failure: a call for objective, reproducible, and
biologically-driven terminology.
PMID- 29943880
TI - Expiratory muscle strength and functional exercise tolerance in adults with
cystic fibrosis: a cross-sectional study.
AB - OBJECTIVE: A 6-minute walk work (6MWW), that is the product of distance walked at
the 6-minute walk test (6MWT) multiplied by body weight, has been suggested as an
appropriate variable for estimating functional capacity. Under the hypothesis
that 6MWW strongly correlates with expiratory muscle strength (PE max), as found
in Chronic Obstructive Pulmonary Disease (COPD), the aim of the study was to
determine the degree of this correlation in adults with cystic fibrosis. METHODS:
A cross-sectional study was carried out at the Regional Referral Centre for
Cystic Fibrosis, where patients with cystic fibrosis attending their regular
follow-up, aged 18 years or older with mild-to-normal lung disease, were asked to
participate. Dietitians determined nutritional status before subjects performed
spirometry and static measurement of respiratory muscles. The 6MWT was performed
as the last study procedure. Spearman correlation test was used to correlate PE
max with 6MWW and other study variables. RESULTS: Twenty-five cystic fibrosis
subjects aged 18-30 years and with FEV1 values ranging from 42.4% to 123.4%
predicted completed the study. PE max strongly correlated with 6MWW (rho .72, p =
.0001) whereas it did not correlate with other study variables, including
distance at the 6MWT. Distance walked multiplied by body weight (p = .0019) and
body mass index (p = .0238) were significantly lower in those with PE max below
the lower limits of normal. CONCLUSION: Increased functional exercise tolerance
is related to higher static expiratory pressure in patients with mild-to-normal
cystic fibrosis lung disease. Difference in exercise performance might reflect a
possible difference in body composition that needs to be further investigated.
PMID- 29943881
TI - Systematic review and meta-analysis of robotic versus open hepatectomy.
AB - BACKGROUND: To date, there are few studies comparing the outcomes of robotic
hepatectomy (RH) versus open hepatectomy (OH). We report the first systematic
review and meta-analysis comparing the outcomes of RH versus OH. METHODS: A
systemic review was performed of all comparative studies of RH versus OH that
reported the perioperative outcome(s) of interest. RESULTS: Seven retrospective
cohort studies were included. There was no significant difference in patients'
baseline characteristics. RH was associated with a longer operation time (mean
difference (MD) 61.47 min; 95% confidence interval (CI) (7.03, 115.91); P =
0.03), shorter hospital stay (MD -2.57 days; 95% CI (-3.31, -1.82); P < 0.001),
lower costs, less overall (risk ratio (RR) 0.63; 95% CI (0.46, 0.86); P = 0.004),
minor (RR 0.64; 95% CI (0.43, 0.95); P = 0.03) and major (RR 0.45; 95% CI (0.22,
0.94); P = 0.03) post-operative complications compared to OH. CONCLUSION: RH had
superior perioperative outcomes and was not cost prohibitive compared to OH, but
had longer operation times.
PMID- 29943882
TI - The clinical outcome of LMNA missense mutations can be associated with the amount
of mutated protein in the nuclear envelope.
AB - AIMS: Lamin A/C mutations are generally believed to be associated with a severe
prognosis. The aim of this study was to investigate disease expression in three
affected families carrying different LMNA missense mutations. Furthermore, the
potential molecular disease mechanisms of the mutations were investigated in
fibroblasts obtained from mutation carriers. METHODS AND RESULTS: A LMNA
p.Arg216Cys missense mutation was identified in a large family with 36 mutation
carriers. Disease expression was unusual with a late onset and a favourable
prognosis. Two smaller families with severe disease expression were shown to
carry a LMNA-p.Arg471Cys and LMNA-p.Arg471His mutation, respectively. LMNA gene
and protein expression was investigated in eight different mutation carriers by
quantitative reverse transcriptase polymerase chain reaction, Western blotting,
immunohistochemistry, and protein mass spectrometry. The results showed that all
mutation carriers incorporated mutated lamin protein into the nuclear envelope.
Interestingly, the ratio of mutated to wild-type protein was only 30:70 in LMNA
p.Arg216Cys carriers with a favourable prognosis while LMNA-p.Arg471Cys and LMNA
p.Arg471His carriers with a more severe outcome expressed significantly more of
the mutated protein by a ratio of 50:50. CONCLUSION: The clinical findings
indicated that some LMNA mutations may be associated with a favourable prognosis
and a low risk of sudden death. Protein expression studies suggested that a
severe outcome was associated with the expression of high amounts of mutated
protein. These findings may prove to be helpful in counselling and risk
assessment of LMNA families.
PMID- 29943883
TI - Measuring detachment of Aspergillus niger spores from colonies with an atomic
force microscope.
AB - Detachment of fungal spores from moldy surfaces and the subsequent aerosolization
can lead to adverse health effects. Spore aerosolization occurs when the forces
for aerosolization exceed the binding forces of spores with their colonies. The
threshold force to detach a spore from a growing colony remains unknown. This
investigation measured the detachment of spores of Aspergillus niger from a
colony using an atomic force microscope (AFM). The spores were first affixed to
the cantilever of the AFM with ultraviolet curing glue, and then, the colony was
moved downward until the spores detached. The threshold detachment forces were
inferred from the deflection of the cantilever. In addition, the spores were
aerosolized in a wind tunnel by a gradual increase of the blowing air speed. The
forces measured by the AFM were compared with the hydrodynamic forces for
aerosolization. The AFM measurements revealed that a force of 3.27 +/- 0.25 nN
was required to detach a single spore from the 4-day-old colony, while 1.98 +/-
0.13 nN was sufficient for the 10-day-old colony. Slightly smaller detachment
forces were observed by the AFM than were determined by the aerosolization tests.
PMID- 29943884
TI - The misperception of 'stable' heart failure.
PMID- 29943885
TI - Exercise elicits dynamic changes in extravascular lung water and haemodynamic
congestion in heart failure patients with preserved ejection fraction.
PMID- 29943886
TI - Low serum chloride in patients with chronic heart failure: clinical associations
and prognostic significance.
AB - BACKGROUND: Low serum chloride is common in patients with chronic heart failure
(CHF) and is associated with worse outcomes. We investigated the clinical and
prognostic associations, including cause of death associations, of low serum
chloride in patients referred to a secondary care clinic with suspected heart
failure. METHODS AND RESULTS: Patients with echocardiogram and serum chloride
were evaluated (n = 5613). CHF was defined as signs and symptoms of the disease
and either left ventricular systolic dysfunction (LVSD) worse than mild [heart
failure with reduced ejection fraction (HFrEF)] or LVSD mild or better and raised
amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (>125 ng/L)
[heart failure with preserved ejection fraction (HFpEF)]. Hypochloraemia was
defined as greater than two standard deviations below the mean in the local
normal distribution (<96 mmol/L). Of the 5613 patients referred, 908 patients did
not have CHF, 1988 had HFrEF, and 2717 had HFpEF. Compared to patients in the
fourth quartile (median chloride 106 mmol/L), patients in the first quartile
(median chloride 96 mmol/L) had more severe symptoms (38% New York Heart
Association class III or IV vs. 25%, P < 0.001) and were more likely to take loop
diuretics (79% vs. 55%, P < 0.001). The annual mortality rate for patients with
CHF was 11%. Hypochloraemia was associated with an increased risk of death
independent of NT-proBNP. Patients in the first quartile had a two-fold increased
risk of death compared to patients in the fourth quartile (P < 0.001). Sudden
death was a common mode of death amongst patients with hypochloraemia.
CONCLUSIONS: Hypochloraemia is strongly related to an adverse prognosis and may
be a therapeutic target in patients with CHF.
PMID- 29943887
TI - Cancer and heart failure-more than meets the eye: common risk factors and co
morbidities.
PMID- 29943888
TI - Use of an ocular wound chamber for the prevention of exposure keratopathy in a
guinea pig model.
AB - Current therapies available to treat and heal ocular surface injuries and
periocular burns are frequently inadequate, costly, and labor intensive. To
address these limitations, we have employed a flexible, semitransparent ocular
wound chamber (OWC) to provide protection as well as a watertight seal to allow
for the constant delivery of therapeutics to the ocular surface and surrounding
periocular tissue. This study demonstrates the safety and utilization of the OWC
on uninjured eyes and in our exposure keratopathy model. For initial safety
studies (N = 3 per group), the eyelids remained intact and the eye uninjured. A
blepharotomy (N = 6 per group) was performed to remove the upper and lower
eyelids surrounding the left (OS) eye to create our exposure keratopathy model.
Right (OD) eyes served as uninjured controls in all studies. Following OWC
placement, 0.5 mL HPMC gel or balanced saline solution (BSS) was injected into
the chamber. Animals were monitored daily and fully assessed via white light,
fluorescein, and OCT imaging at least through 72 hours post OWC placement. In
studies that included a blepharotomy, skin samples were analyzed by multiplex
cytokine analysis. Results of safety experiments revealed no significant
differences between treatment groups in corneal thickness, fluorescein staining,
OCT imaging, or histological eye or skin sections when compared to control eyes.
In our exposure keratopathy model, OWC treated eyes showed significantly less
fluorescein uptake and also were found to have significantly lower levels of
cytokines IL-13 and IL-5 in skin samples. These results demonstrate for the first
time that treatment using the OWC device is not only safe, but significantly
protects against blepharotomy-induced exposure keratopathy. As a whole, this
study advances our overall efforts to develop a feasible solution to treat ocular
surface injuries, infections, and periocular burns.
PMID- 29943889
TI - Preconception care for infertile couples: Nurses' and midwives' roles in
promoting better maternal and birth outcomes.
AB - INTRODUCTION: Preconception care promotes better maternal outcomes, may assist in
preventing birth defects and improves fertility awareness among healthy
childbearing couples. Yet, the significance of preconception care for infertile
couples is undeveloped area of practice in Europe. AIMS AND OBJECTIVES: To
discuss the importance of nurses and midwives in providing preconception care to
infertile couples in the United Kingdom and Spain. DESIGN: Discursive paper.
METHOD: A comparison of different midwifery and nursing approaches to
preconception care for infertile couples in two European countries. FINDINGS: At
present, infertile couples' needs for preconception care are not routinely
identified or understood. There is an opportunity for these needs to be
considered and identified by nurses at the time of investigation for infertility
or when planning pregnancy with assisted conception. CONCLUSIONS: We argue that,
by providing preconception care, nurses and midwives have an opportunity to
deliver important advice to infertile couples in both primary care and specialist
infertility services.
PMID- 29943890
TI - Multi-ethnic comparisons of diabetes in heart failure with reduced ejection
fraction: insights from the HF-ACTION trial and the ASIAN-HF registry.
AB - AIM: To describe differences in patient characteristics and outcomes by ethnicity
in patients with diabetes mellitus (DM) and heart failure (HF) with reduced
ejection fraction (HFrEF, ejection fraction <=35%) in a multi-ethnic cohort.
METHODS AND RESULTS: Patient level data from two cohorts (HF-ACTION and ASIAN-HF)
were combined, and patients grouped by self-reported ethnicity. DM was defined as
the presence of a clinical diagnosis and/or receiving anti-diabetic therapy. A
total of 6214 (1324 whites, 674 blacks, 1297 Chinese, 1510 Indians, 717 Malays,
692 Japanese/Koreans) patients were included. The overall prevalence of DM was
39.5% (n = 2454). The prevalence of DM was lowest in whites (29.3%), followed by
Japanese/Koreans (34.1%), blacks (35.9%), Chinese (42.3%), Indians (44.2%), and
highest in Malays (51.9%). The correlation between age, sex, body mass index,
coronary artery disease, hypertension, atrial fibrillation, peripheral vascular
disease and chronic kidney disease with DM differed significantly by ethnicity (P
for interaction <0.05). The strongest correlations were seen in Malay women,
whites with obesity, Indians with coronary artery disease and hypertension, and
blacks with chronic kidney disease. On multivariable analyses, DM was
significantly associated with the composite of 1-year overall mortality/HF
hospitalization (hazard ratio 1.37, 95% confidence interval 1.19-1.57; P <
0.001), with no interaction by ethnicity (P for interaction =0.31). CONCLUSIONS:
There is marked heterogeneity in the prevalence and correlates of DM among
different ethnic groups with HF worldwide. Subgroups particularly predisposed to
DM warrant special attention, since DM increases the combined risk of morbidity
and mortality in all ethnicities with HF.
PMID- 29943891
TI - Outcome of landmark-guided percutaneously inserted tunneled central venous
catheters in infants and children under 3 years with cancer.
AB - BACKGROUND: There is a paucity of information on procedural and long-term
outcomes of tunneled central venous catheters (TCVC) in infants and children
younger than 3 years undergoing anticancer therapy. This study aims to evaluate
the success, safety, and complications leading to surgical revision or premature
removal of TCVC in this particular patient group. METHODS: The clinical course of
pediatric patients with percutaneous inserted TCVC, including Groshong (GC) and
Hickman/Broviac (HB) catheters, has been analyzed retrospectively. The data
analysis includes patient and device characteristics, adverse events during
insertion, and dwell period complications. RESULTS: A consecutive series of 238
children undergoing implantation of 273 TCVC, including 148 (54.2%) GC and 125
(45.8%) HB catheters, with a total of 38,209 catheter days at risk (cdr) were
reviewed. The patient cohort consisted of 65 (23.8%) infants, 77 (28.2%) children
aged 1-2 years, and 131 (48.0%) aged 2-3 years. The overall rate of adverse
events during catheter insertion was 12.8% (n = 35) with no differences between
age groups or devices. The overall rate of long-term complication was 28.2% (n =
77, catheter risk [CR] per 1,000 cdr = 1.75), with the highest prevalence in
infants (P = 0.01). The most common complication was late dislocation (n = 24,
8.8%, CR = 0.47), followed by early dislocation (n = 20, 7.3%) and infection (n =
18, 7.4%, CR = 0.42). CONCLUSION: Percutaneous landmark-guided insertion of TCVC
in neonates and small children with cancer is safe. Patterns of long-term
complications are different from those for older children and should be prevented
through appropriate management.
PMID- 29943892
TI - Using 4DCT-ventilation to characterize lung function changes for pediatric
patients getting thoracic radiotherapy.
AB - PURPOSE: A form of lung functional imaging has been developed that uses 4DCT data
to calculate ventilation (4DCT-ventilation). Because 4DCTs are acquired as
standard-of-care to manage breathing motion during radiotherapy, 4DCT-ventilation
provides functional information at no extra dosimetric or monetary cost. 4DCT
ventilation has yet to be described in children. 4DCT-ventilation can be used as
a tool to help assess post-treatment lung function and predict for future
clinical thoracic toxicities for pediatric patients receiving radiotherapy to the
chest. The purpose of this work was to perform a preliminary evaluation of 4DCT
ventilation-based lung function changes for pediatric patients receiving
radiotherapy to the lungs. METHODS: The study used four patients with pre and
postradiotherapy 4DCTs. The 4DCTs, deformable image registration, and a density
change-based algorithm were used to compute pre and post-treatment 4DCT
ventilation images. The post-treatment 4DCT-ventilation images were compared to
the pretreatment 4DCT-ventilation images for a global lung response and for an
intrapatient dose-response (providing an assessment for dose-dependent regional
dose-response). RESULTS: For three of the four patients, a global ventilation
decline of 7-37% was observed, while one patient did not demonstrate a global
functional decline. Dose-response analysis did not reveal an intrapatient dose
response from 0 to 20 Gy for three patients while one patient demonstrated
increased 4DCT-ventilation decline as a function of increasing lung doses up to
50 Gy. CONCLUSIONS: Compared to adults, pediatric patients have unique lung
function, dosimetric, and toxicity profiles. The presented work is the first to
evaluate spatial lung function changes in pediatric patients using 4DCT
ventilation and showed lung function changes for three of the four patients. The
early changes demonstrated with lung function imaging warrant further
longitudinal work to determine whether the imaging-based early changes can be
predicted for long-term clinical toxicity.
PMID- 29943893
TI - Evaluation of mobile phone applications to support medication adherence and
symptom management in oncology patients.
AB - Mobile phone applications (apps), may support pediatric oncology patients with
medication and disease management. A scoping review of the literature, a search
of the iTunes App and Google Play Stores, was conducted to identify medication
and symptom management apps for adult and pediatric oncology patients. Pooled
results yielded 28 apps which were assessed for quality using the Mobile
Application Rating Scale, with mean overall scores ranging from 2.8 to 4.3. Most
apps received low scores in the Engagement domain. Our study assessed the quality
of available mobile oncology apps and identified areas for improvement in design
and function.
PMID- 29943894
TI - Recent Advances and Developments of in vitro Evaluation of Heterocyclic Moieties
on Cancer Cell Lines.
AB - Besides worthy development in cancer therapy, cancer is still one of the leading
causes of death, worldwide. The future burden of cancer will probably be even
larger because people are adopting poor lifestyles with poor diet, frequently
smoking and less physical activity. The effective anticancer drugs having
efficacy and selectivity with low toxicity is still a challenge for the
scientific fraternity. The advances in the cancer study have its origin on the
availability of different types of experimental model systems that review the
various forms of this disease. Cell lines emerge as a feasible alternative for
anticancer activities, being at the same time easy to manipulate and molecularly
characterize. Heterocycles are key structural components of many of the anti
cancer drugs available on the market today. Indeed, of the novel molecular anti
cancer agents approved by the FDA between 2010 and 2017, almost two-thirds
contained heterocyclic rings within their structures. This review summarizes and
provides updated literature on heterocyclic compounds using various cancer cell
lines reported during the period of 2014-2017 together with the structure
activity relationships.
PMID- 29943896
TI - Relatively favorable prognosis for MLL-rearranged childhood acute leukemia with
reciprocal translocations.
AB - BACKGROUND: Mixed-lineage leukemia (MLL) with multifarious partner genes leads to
aggressive leukemia with dismal outcomes. METHODS: Using panel-based targeted
sequencing, we examined 90 cases with MLL-rearranged (MLL-r) childhood acute
leukemia, including 55 with acute lymphoblastic leukemia (ALL) and 35 with acute
myeloid leukemia (AML). RESULTS: MLL breakpoints and complete rearrangements were
identified. A total of 37.8% (34/90) of patients displayed a single direct MLL
fusion gene, 15.6% (14/90) carried a single reciprocal fusion, and 27.8% (25/90)
had both reciprocal MLL fusion alleles. The remaining 17 MLL-r cases exhibited
complex translocations with homozygous disruptions on chromosome 11 or two
breakpoints on the same MLL allele with a deletion of functional regions. A total
of 77 patients (45 ALL and 32 AML) received chemotherapy with a median follow-up
of 2.5 years. Unexpectedly, we identified children with reciprocal MLL fusions
who exhibited relatively favorable outcomes compared with those in children with
complex translocations or a single direct MLL fusion allele (66.1% vs. 24.6% and
27.6%, P = 0.001). Reciprocal MLL fusion may be functionally rescued by a
partially truncated MLL protein. CONCLUSION: Comprehensive MLL-r analysis by
targeted next-generation sequencing can provide detailed molecular information
and is helpful for precise stratified treatment and clinical prognosis
determination.
PMID- 29943895
TI - Improving accuracy for stereotactic body radiotherapy treatments of spinal
metastases.
AB - PURPOSE: Use of SBRT techniques is now a relatively common recourse for spinal
metastases due to good local control rates and durable pain control. However, the
technique has not yet reached maturity for gantry-based systems, so work is still
required in finding planning approaches that produce optimum conformity as well
as delivery for the slew of treatment planning systems and treatment machines.
METHODS: A set of 32 SBRT spine treatment plans based on four vertebral sites,
varying in modality and number of control points, were created in Pinnacle. These
plans were assessed according to complexity metrics and planning objectives as
well as undergoing treatment delivery QA on an Elekta VersaHD through ion chamber
measurement, ArcCheck, film-dose map comparison and MLC log-file reconstruction
via PerFraction. RESULTS: All methods of QA demonstrated statistically
significant agreement with each other (r = 0.63, P < 0.001). Plan complexity and
delivery accuracy were found to be independent of MUs (r = 0.22, P > 0.05) but
improved with the number of control points (r = 0.46, P < 0.03); with use of 90
control points producing the most complex and least accurate plans. The fraction
of small apertures used in treatment had no impact on plan quality or accuracy (r
= 0.29, P > 0.05) but rather more complexly modulated plans showed poorer results
due to MLC leaf position inaccuracies. Plans utilizing 180 and 240 control points
produced optimal plan coverage with similar complexity metrics to each other.
However, plans with 240 control points demonstrated slightly better delivery
accuracy, with fewer MLC leaf position discrepancies. CONCLUSION: In contrast to
other studies, MU had no effect on delivery accuracy, with the most impactful
parameter at the disposal of the planner being the number of control points
utilized.
PMID- 29943897
TI - Exposure to polycyclic aromatic hydrocarbons, vitamin D, and lung function in
children with asthma.
AB - BACKGROUND: It is unclear whether exposure to polycyclic aromatic hydrocarbons
(PAH) affects lung function in children with asthma. Whether vitamin D
insufficiency enhances any detrimental effects of PAH on lung function in
asthmatic children is also unknown. METHODS: Cross-sectional study of 1,821
children (6-17 years) who participated in the 2007-2012 National Health and
Nutrition Examination Survey. Multivariable linear regression was used to analyze
the relation between molar mass of urinary PAH metabolites (sum of all PAH
(SigmamolPAH), sum of PAH with 2 benzene rings (Sigmamol2-PAH), or sum of PAH
with 3 or 4 benzene rings (Sigmamol3,4-PAH)) and lung function or exhaled
fraction of nitric oxide (FeNO) in children with and without asthma. In this
multivariable analysis, we tested whether vitamin D insufficiency (a serum
25(OH)D level <30 ng/mL) interacts with PAH exposure on lung function in children
with asthma. RESULTS: Children in the highest quartiles of urinary Sigmamol3,4
PAH had 2.3 times increased odds of asthma than those in the lowest quartile of
Sigmamol3,4-PAH. Urinary PAH were not associated with lung function in children
with or without asthma. Given a significant interaction between vitamin D
insufficiency and PAH metabolites on lung function in asthmatic children, we
stratified the analysis by vitamin D status. In this analysis, urinary PAH
metabolites were significantly associated with 2.7-3.9% reduced %predicted FEV1
and %predicted FEV1/FVC in children with asthma and vitamin D insufficiency, but
not in those with asthma and vitamin D sufficiency. CONCLUSIONS: Vitamin D
insufficiency and PAH exposure may have synergistic detrimental effects on lung
function in asthmatic children.
PMID- 29943898
TI - Reliably discriminating stock structure with genetic markers: Mixture models with
robust and fast computation.
AB - Delineating naturally occurring and self-sustaining subpopulations (stocks) of a
species is an important task, especially for species harvested from the wild.
Despite its central importance to natural resource management, analytical methods
used to delineate stocks are often, and increasingly, borrowed from superficially
similar analytical tasks in human genetics even though models specifically for
stock identification have been previously developed. Unfortunately, the
analytical tasks in resource management and human genetics are not identical
questions about humans are typically aimed at inferring ancestry (often referred
to as "admixture") rather than breeding stocks. In this article, we argue, and
show through simulation experiments and an analysis of yellowfin tuna data, that
ancestral analysis methods are not always appropriate for stock delineation. In
this work, we advocate a variant of a previously introduced and simpler model
that identifies stocks directly. We also highlight that the computational aspects
of the analysis, irrespective of the model, are difficult. We introduce some
alternative computational methods and quantitatively compare these methods to
each other and to established methods. We also present a method for quantifying
uncertainty in model parameters and in assignment probabilities. In doing so, we
demonstrate that point estimates can be misleading. One of the computational
strategies presented here, based on an expectation-maximization algorithm with
judiciously chosen starting values, is robust and has a modest computational
cost.
PMID- 29943899
TI - Light exposure via a head-mounted device suppresses melatonin and improves
vigilant attention without affecting cortisol and comfort.
AB - We aimed at assessing whether a head-mounted light therapy device, enriched in
blue wavelengths, suppresses melatonin secretion and improves vigilant attention
in the late evening hours. We also assessed whether using such light device is
associated with discomfort and physiological stress. Seventeen healthy young
participants (eight females) participated in a counterbalanced within-subject
design during which they were exposed for 2 hr before habitual sleep time to a
blue-enriched light (1500 lx) or to a lower intensity red-light (150 lx) control
condition, using a new-generation light emitting diode (LED) head-mounted device.
Compared to the red light control condition, blue-enriched light significantly
reduced melatonin secretion and reaction times during a psychomotor vigilance
task while no significant differences were detected in discomfort and cortisol
levels. These results suggest that, compared to a control condition, blue
enriched light, delivered by a new-generation head-mounted device, elicits
typical non-visual responses to light without detectable discomfort and
physiological stress. They suggest that such devices might constitute an
effective alternative to standard light boxes.
PMID- 29943900
TI - Measures that matter: Health-related quality of life in children with
interstitial lung disease.
PMID- 29943901
TI - The association between gender and pediatric respiratory morbidity.
AB - OBJECTIVE: To evaluate the association between newborn gender and the risk for
later pediatric respiratory morbidity. STUDY DESIGN: A population based cohort
analysis was performed by comparing the risk of long-term respiratory morbidity
(until 18 years of age) according to gender. Respiratory morbidity included
hospitalizations involving pneumonia, asthma, bronchitis, bronchiolitis, upper
respiratory tract infection (URTI), influenza, and bronchiectasis. Deliveries
occurred between the years 1991 and 2014 in a tertiary medical center. Kaplan
Meier survival curves were constructed to compare cumulative respiratory
morbidity. A Cox proportional hazards model controlled for confounders. RESULTS:
During the study period 240 953 newborns met the inclusion criteria. Among them,
118 113 were females (49.0%) and 122 840 were males (51.0%). During the 18 years
of follow-up, 13 719 (5.7%) different newborns were hospitalized with respiratory
related morbidity. Males had significantly higher rates of respiratory morbidity
as compared with females (6.4% vs 4.9% respectively, P < 0.001, OR 1.32, 95% CI
1.28-1.37). Specifically, pneumonia, bronchitis, asthma, bronchiolitis, and URTI
were significantly more common in males. Males exhibited higher total cumulative
respiratory morbidity (log rank P < 0.001), as well as higher cumulative
morbidity in several sub-categories. These sub-categories included pneumonia,
bronchitis, asthma, bronchiolitis, and URTI (P < 0.05 in all). The Cox regression
model demonstrated male gender to be an independent risk factor for pediatric
respiratory morbidity while adjusting for gestational age, birthweight, and other
confounders (HR 1.29, 95% CI 1.25-1.34, P < 0.001). CONCLUSIONS: Males are at an
increased risk for pediatric respiratory morbidity, independent of obstetrical
characteristics such as gestational age and birthweight.
PMID- 29943903
TI - Tick-borne relapsing fever as a potential veterinary medical problem.
AB - Tick-borne relapsing fever (TBRF) caused by the bacteria Borrelia, is poorly
documented in veterinary medicine. Given the widespread presence of the soft tick
vectors - Ornithodoros and the recently discovered hard tick vectors, as well as
their close association with animal hosts, it is highly likely that infection
occurs, but is rarely reported to be of veterinary importance. Sporadic reports
of canine infection, some being fatal through to probable cause of abortion in
horses have been published. Some of these pathogens exist in regions where there
are limited diagnostic facilities, hence, they are likely to be missed and their
impact on productivity may be unquantified. Here we review available literatures
on cases of TBRF in domestic and wild animals in order to show their potential
veterinary medical impact. Future efforts using field and laboratory surveys are
needed to determine pathogenesis, vector competence and distribution in animals,
their impact on animal health and productivity as well as to prevent further
spill to the human population, where it is already a public health problem in
some parts of the world.
PMID- 29943904
TI - The viability and necessity of APRN-led care models in the clinical management of
haemophilia and other inherited bleeding and clotting disorders.
AB - A growing and ageing haemophilia treatment centre (HTC) population, as well as a
glaring shortage of adult haematologists available for the clinical management of
persons with haemophilia (PWH), has resulted in significant care gaps in the
United States. In response, various advanced practice registered nurse (APRN)
based models have been adopted across the country to counteract a deficit in
haematologist resources for adult PWH. These models in the management of PWH have
demonstrated competency and efficiency in the care of patients with haemophilia,
offering a viable solution in areas where haematologist resources are limited and
assure quality care provision, most notably in rural areas. The available
literature indicates equivalence in terms of clinical outcomes, patient
satisfaction and elements of healthcare service utilization. With continued
support in current clinical guidelines and institutional contributions in the
form of residency and fellowship programmes, the robust successes of APRN models
for the clinical management of PWH can be maintained and expanded well into the
foreseeable future.
PMID- 29943902
TI - A novel cardiac output response to stress test developed to improve diagnosis and
monitoring of heart failure in primary care.
AB - AIMS: Primary care physicians lack access to an objective cardiac function test.
This study for the first time describes a novel cardiac output response to stress
(CORS) test developed to improve diagnosis and monitoring of heart failure in
primary care and investigates its reproducibility. METHODS AND RESULTS:
Prospective observational study recruited 32 consecutive primary care patients
(age, 63 +/- 9 years; female, n = 18). Cardiac output was measured continuously
using the bioreactance method in supine and standing positions and during two 3
min stages of a step-exercise protocol (10 and 15 steps per minute) using a 15 cm
height bench. The CORS test was performed on two occasions, i.e. Test 1 and Test
2. There was no significant difference between repeated measures of cardiac
output and stroke volume at supine standing and Stage 1 and Stage 2 step
exercises (all P > 0.3). There was a significant positive relationship between
Test 1 and Test 2 cardiac outputs (r = 0.92, P = 0.01 with coefficient of
variation of 7.1%). The mean difference in cardiac output (with upper and lower
limits of agreement) between Test 1 and Test 2 was 0.1 (-1.9 to 2.1) L/min,
combining supine, standing, and step-exercise data. CONCLUSIONS: The CORS, as a
novel test for objective evaluation of cardiac function, demonstrates acceptable
reproducibility and can potentially be implemented in primary care.
PMID- 29943905
TI - Comparing osteonecrosis clinical phenotype, timing, and risk factors in children
and young adults treated for acute lymphoblastic leukemia.
AB - BACKGROUND: Treatment-related osteonecrosis (ON) is a serious complication of
treatment of acute lymphoblastic leukemia (ALL). PROCEDURE: This study included
1,489 patients with ALL, aged 1-45 years, treated according to the Nordic Society
of Paediatric Haematology and Oncology ALL2008 protocol, using alternate-week
dexamethasone during delayed intensification, with prospective registration of
symptomatic ON. We aimed at comparing risk factors, timing, and clinical
characteristics of ON in children and young adults. RESULTS: ON was diagnosed in
67 patients, yielding a 5-year cumulative incidence of 6.3%, but 28% in female
adolescents. Median age at ALL diagnosis was 12.1 years and 14.9 years for
females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%)
and 30 (46%) had multiple-joint involvement. The median interval between ALL and
ON diagnosis was significantly shorter in children aged 1.0-9.9 years (0.7 years
[range: 0.2-2.1]) compared with adolescents (1.8 years [range: 0.3-3.7, P <
0.001]) and adults (2.1 years [range: 0.4-5.3, P = 0.001]). Female sex was a risk
factor in adolescent patients (hazard ratio [HR] = 2.1, 95% confidence interval
[CI]: 1.1-4.2) but not in children aged 1.1-9.9 years (HR = 2.4, 95% CI: 0.9-6.2,
P = 0.08) or adults aged 19-45 years (HR = 1.1, 95% CI: 0.3-4.0). Age above 10
years at ALL diagnosis (odds ratio [OR] = 3.7, P = 0.026) and multiple joints
affected at ON diagnosis (OR = 3.4, P = 0.027) were risk factors for developing
severe ON. CONCLUSION: We provide a detailed phenotype of patients with ALL with
symptomatic ON, including description of risk factors and timing of ON across age
groups. This awareness is essential in exploring measures to prevent development
of ON.
PMID- 29943907
TI - Revisiting pleuropulmonary blastoma and atypical choroid plexus papilloma in a
young child: DICER1 syndrome or not?
PMID- 29943906
TI - Deciphering the mechanism of potent peptidomimetic inhibitors targeting
plasmepsins - biochemical and structural insights.
AB - : Malaria is a deadly disease killing worldwide hundreds of thousands people each
year and the responsible parasite has acquired resistance to the available drug
combinations. The four vacuolar plasmepsins (PMs) in Plasmodium falciparum
involved in hemoglobin (Hb) catabolism represent promising targets to combat drug
resistance. High antimalarial activities can be achieved by developing a single
drug that would simultaneously target all the vacuolar PMs. We have demonstrated
for the first time the use of soluble recombinant plasmepsin II (PMII) for
structure-guided drug discovery with KNI inhibitors. Compounds used in this study
(KNI-10742, 10743, 10395, 10333, and 10343) exhibit nanomolar inhibition against
PMII and are also effective in blocking the activities of PMI and PMIV with the
low nanomolar Ki values. The high-resolution crystal structures of PMII-KNI
inhibitor complexes reveal interesting features modulating their differential
potency. Important individual characteristics of the inhibitors and their
importance for potency have been established. The alkylamino analog, KNI-10743,
shows intrinsic flexibility at the P2 position that potentiates its interactions
with Asp132, Leu133, and Ser134. The phenylacetyl tripeptides, KNI-10333 and KNI
10343, accommodate different rho-substituents at the P3 phenylacetyl ring that
determine the orientation of the ring, thus creating novel hydrogen-bonding
contacts. KNI-10743 and KNI-10333 possess significant antimalarial activity,
block Hb degradation inside the food vacuole, and show no cytotoxicity on human
cells; thus, they can be considered as promising candidates for further
optimization. Based on our structural data, novel KNI derivatives with improved
antimalarial activity could be designed for potential clinical use. DATABASE:
Structural data are available in the PDB under the accession numbers 5YIE, 5YIB,
5YID, 5YIC, and 5YIA.
PMID- 29943908
TI - Meeting report of the STAR-Sensitization in Transplantation Assessment of Risk:
Naive Abdominal Transplant Organ subgroup focus on kidney transplantation.
AB - The development of de novo donor-specific HLA antibody (dnDSA) is a critical
feature contributing to late allograft failure. The complexity of the issue is
further complicated by organ-specific differences, detection techniques, reliance
of tissue histopathology and changing diagnostic criteria, ineffective therapies,
and lack of consensus. To tackle these issues, the Sensitization in
Transplantation Assessment of Risk (STAR) 2017 was initiated as a collaboration
of the American Society of Transplantation and American Society of
Histocompatibility and Immunogenetics consisting of 8 working groups with the
goal to provide guidelines on how to assess risk and risk stratify patients based
on their potential alloimmune and DSA status. Herein is a summary of discussions
by the Naive Abdominal Working Group, highlighting currently available data and
identifying gaps in our knowledge on the development and impact of dnDSA
following kidney transplantation.
PMID- 29943909
TI - Minimally invasive preservation versus splenectomy during distal pancreatectomy:
a systematic review and meta-analysis.
AB - BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) has gained in
popularity recently. However, there is no consensus on whether to preserve the
spleen or not. In this study, we compared MIDP outcomes between spleen-preserving
distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS); as
well as outcomes between splenic vessel preservation (SVP) and Warshaw's
technique (WT). METHODS: A systematic search of PubMed (MEDLINE) and Cochrane
Library was conducted and the reference lists of review articles were hand
searched. RESULTS: Fifteen relevant studies with 769 patients were selected for
meta-analyses of DPS and SPDP, while another 15 studies with 841 patients were
used for the analysis between SVP and WT. Compared with the DPS group, SPDP
patients had significantly lower incidences of infectious complications (P =
0.006) and pancreatic fistula (P = 0.002), shorter operative time (P < 0.001),
and less blood loss (P = 0.01). Compared with WT, SVP patients had significantly
lower incidences of splenic infarction (P < 0.001) and secondary splenectomy (P =
0.003). Subanalysis for laparoscopic surgery alone had similar results.
CONCLUSIONS: Based on this study, SPDP has significantly superior outcomes
compared to DPS. When a spleen is preserved, SVP has better outcomes over WT for
reducing splenic complications.
PMID- 29943910
TI - 3D printing technology will eventually eliminate the need of purchasing
commercial phantoms for clinical medical physics QA procedures.
PMID- 29943911
TI - A palmitoyltransferase Approximated gene Bm-app regulates wing development in
Bombyx mori.
AB - The silkworm Bombyx mori is an important lepidopteran model insect in which many
kinds of natural mutants have been identified. However, molecular mechanisms of
most of these mutants remain to be explored. Here we report the identification of
a gene Bm-app is responsible for the silkworm minute wing (mw) mutation which
exhibits exceedingly small wings during pupal and adult stages. Compared with the
wild type silkworm, relative messenger RNA expression of Bm-app is significantly
decreased in the u11 mutant strain which shows mw phenotype. A 10 bp insertion in
the putative promoter region of the Bm-app gene in mw mutant strain was
identified and the dual luciferase assay revealed that this insertion decreased
Bm-app promoter activity. Furthermore, clustered regularly interspaced short
palindromic repeats/RNA-guided Cas9 nucleases-mediated depletion of the Bm-app
induced similar wing defects which appeared in the mw mutant, demonstrating that
Bm-app controls wing development in B. mori. Bm-app encodes a
palmitoyltransferase and is responsible for the palmitoylation of selected
cytoplasmic proteins, indicating that it is required for cell mitosis and growth
during wing development. We also discuss the possibility that Bm-app regulates
wing development through the Hippo signaling pathway in B. mori.
PMID- 29943912
TI - Interleukin 1 receptor antagonist (IL1RA) gene polymorphism and levels associated
with adverse outcome in severe community-acquired pneumonia in children: A
hospital-based study in India.
AB - BACKGROUND: High morbidity and mortality due to community-acquired pneumonia
(CAP) is seen in children under 5 years of age in India. Besides identified risk
factors for CAP, there may be a phenotype-genotype association with cytokines,
resulting in enhanced inflammatory response resulting in the adverse outcome
(AO), namely complications and death. AIM: To assess the association of IL1RA
gene polymorphism on serum levels of IL1RA and with AO in children under 5 years
of age hospitalized with WHO-defined severe CAP. METHOD: A prospective cohort
study with nested case-control design conducted in a tertiary care teaching
hospital after obtaining institutional ethical approval. Included were children
between 2 and 59 months of age hospitalized with WHO-defined severe CAP with
consistent radiological abnormalities. Excluded were those with suspected or
proven cystic fibrosis, pulmonary tuberculosis, malignancy, immunodeficiency, and
congenital heart disease. Polymerase chain reaction (PCR) was used to analyze the
Variable Number of Tandem Repeats (VNTRs) of IL1RA gene polymorphism and ELISA
test to detect serum levels of IL1RA. RESULTS: From 2014 to 2016, of 420 screened
cases, 350 were eligible and included, of which 132 (37.7%) had no complication
and 218 (62.3%) had AO, which included complications like empyema,
pyopneumothorax, acute respiratory distress syndrome (ARDS), and septic shock of
these 24 (6.9%) expired. Higher risk of AO was seen in A2A2 genotype (OR 11.18, p
0.0001) and lower in A1A1 genotype (OR 0.18, P < 0.0001). Serum IL1RA (ng/mL) was
statistically significantly elevated in CAP with AO (2.55 +/- 1.44) versus
uncomplicated (0.87 +/- 0.52) (P < 0.0001). CONCLUSION: In IL1RA gene, A1A1
genotype was associated with lower risk and A2A2 genotype with increased the risk
of AO. Higher serum levels of IL1RA were found in A2A2 genotype indicating
possibly enhanced inflammatory response resulting in AO of CAP.
PMID- 29943913
TI - Eosinophilic granulomatosis with polyangiitis in children: Data from the French
RespiRare(r) cohort.
AB - OBJECTIVES: To describe the characteristics of pediatric cases of eosinophilic
granulomatosis with polyangiitis (EGPA), a systemic necrotizing vasculitis rarely
diagnosed in children, retrieved from the French Reference Center for rare
pediatric lung diseases and compared with adult cases included in the French
Vasculitis Study Group cohort. METHODS: We collected information on pediatric
EGPA disease presentation, management, and outcome. Cases met the Lanham criteria
and/or American College of Rheumatology classification criteria. RESULTS:
Fourteen cases of pediatric EGPA were included, from 1980 to 2012, with a median
follow-up of 58.5 months. Median age at diagnosis was 12.3 years. All cases had
respiratory involvement. The organ systems most frequently involved were the
upper airway (85%), skin (71%), digestive tract (64%), and heart (57%).
Neurological and renal involvement were rare. Four of the fourteen children were
positive for ANCA (30.7%). During follow-up, three children required intensive
care and one child died. The relapse rate was 64%. In comparison with an adult
cohort, we found more ENT, heart, and digestive-tract involvement, and fewer
neurological manifestations. In children, the delay between asthma onset and
diagnosis was shorter, and biopsies showed fewer features of vasculitis.
CONCLUSION: This French cohort is the biggest pediatric EGPA series described to
date, with a long follow-up period. The findings confirm that pediatric EGPA has
specific clinical, radiological, and histological characteristics that differ
from adult EGPA. Development of systemic symptoms, and consequently diagnosis,
occur with a shorter delay in children, mainly during the eosinophilic phase and
leading to a specific presentation.
PMID- 29943914
TI - Detection of Plasma Curcuminoids from Dietary Intake of Turmeric-Containing Food
in Human Volunteers.
AB - SCOPE: Curcumin (from turmeric), has been extensively investigated for potential
beneficial properties in numerous diseases. Most work has focused on supra
dietary concentrations/doses that would necessitate curcumin supplementation.
However, much evidence instigating curcumin research is underpinned by
epidemiological data based on low dietary intake via turmeric consumption.
METHODS AND RESULTS: Here, a novel, highly sensitive liquid chromatography
electrospray ionization-mass spectrometry (LC-ESI-MS/MS) method for detection of
curcuminoids is described. Assay sensitivity is demonstrated in a pilot
pharmacokinetic volunteer study following ingestion of foodstuffs containing a
standardized mass of turmeric, representative of daily consumption by certain
South Asian populations. Free parent curcumin was detectable in plasma from one
individual, reaching maximal plasma concentrations (Cmax ) of 3.2 nm. Curcumin
conjugates were detected in all volunteers; Cmax for curcumin glucuronide is 47.6
+/- 28.5 nm 30 min post-food, while Cmax for demethoxycurcumin glucuronide and
curcumin sulfate is ~2 nm. Curcumin and its major metabolites persist in plasma
for at least 8 h. CONCLUSION: Despite poor absorption and rapid conjugation,
dietary intake of standard culinary turmeric within complex food matrices
furnished human plasma with detectable levels of curcuminoids. Whether sustained
low systemic concentrations of these non-nutritive, biologically active, dietary
components may have pharmacological activity for human health benefit, warrants
further research.
PMID- 29943915
TI - Does lung microbiome play a causal or casual role in asthma?
AB - Asthma is the most common chronic disease in childhood. The pathogenesis of
asthma is multifactorial and is thought to include environmental factors
interacting with genetics during pregnancy and in the first years of life. In the
last decades, a possible role of gut microbiota in allergic disease pathogenesis
has been demonstrated. Next generation sequencing techniques have allowed the
identification of a distinct microbiome in the healthy lungs. The lung microbiome
is characterized by the prevalence of bacteria belonging to the phylum
Bacteroidetes (mostly Prevotella and Veilonella spp) in healthy subjects and to
the phylum Proteobacteria in asthmatics (mostly Haemophilus, Moraxella, and
Neisseria spp). In asthma, as well as in other diseases, the lung microbiome
composition changes due to a disruption of the delicate balance between
immigration and elimination of bacteria. The lung microbiome can interact with
the immune system, thus influencing inflammation. Early infections with viruses,
such as respiratory syncytial virus, may alter lung microbiome composition
favoring the emergence of Proteobacteria, a phylum which is also linked to
severity of asthma and bronchial hyperreactivity. Lastly, antibiotics may alter
the gut and lung microbiota and potentially disturb the relationship between
microbiota and host. Therefore, antibiotics should be prescribed with increasing
awareness of their potential harmful effect on the microbiota in young children
with and without asthma. The potential effects of probiotics and prebiotics on
lung microbiome are unknown.
PMID- 29943916
TI - MiRNAs: regulators of human disease.
AB - MicroRNAs (miRNAs) represent the mediators of important leading biological
functions of molecular pathways in humans. They are a class of very small, non
coding RNAs; their function is the balance of the protein levels at the post
transcriptional stage. They are implicated in molecular processes and diseases,
including diabetes, metabolism, autoimmune diseases, angiogenesis and
tumorigenesis, and female fertility, exhibiting an altered expression profile.
Any process taking place in the human organism is intertwined by miRNAs. MiRNAs
have an impact on the biochemistry of pathways of the invisible molecular world.
They circulate in a stable chemical configuration in body fluids (tears, serum,
plasma, amniotic fluid, ascetic fluid, urine) with their molecular sequence
specificity remaining unchanged. Their indisputable molecular stability ranks
them as extremely vigorous potential markers in human disease. MiRNAs demonstrate
a specific expressive signature, representative of the tissue specificity and the
clinical staging. The shift on the concentration and expression of a miRNA
reflects the course of a disease. MiRNAs may operate as oncogenes (tumor growth)
or tumor suppressor (tumor reduction) genes in cancer pathways. In malignant
disease, proliferation, maintenance, and progression of cancer cells is induced
by the stimulation of the oncogenes or complete deactivation of the tumor
suppressor gene activity.
PMID- 29943917
TI - A novel surgical technique for the large ovarian cystic mass - combined mini
laparotomy and laparoscopy.
AB - BACKGROUND: Laparoscopic resection of ovarian cysts > ten cm in diameter can be
technically challenging. Laparotomy is often the preferred surgical approach.
Minimal access surgery in gynaecology has been compared to laparotomy and has
been shown to result in shorter patient hospital length of stay, reduced post
operative pain, and faster return to routine activities. Minimal access surgical
techniques for ovarian masses > ten cm are therefore of interest as they may
offer significant benefits. OBJECTIVE: To assess the feasibility of a novel
surgical technique using a combination of both laparoscopy and mini-laparotomy in
the surgical management of ovarian cystic masses > ten cm. Outcomes including
hospital length of stay, return to usual activities, post-operative
complications, and patient satisfaction were assessed. MATERIALS AND METHODS: A
total of 17 patients who underwent surgery by a gynaecologic oncologist at a
tertiary institution in Western Australia from June 2012 to September 2013 were
selected. The risk of malignancy index was used to triage patients. A mini
laparotomy incision was utilised to downsize the mass and to retrieve the
specimen, while the remainder of the procedure was performed by laparoscopy.
Medical records were used to collect post-operative and follow up data. Patient
satisfaction at six weeks post-surgery was analysed by means of a telephone
questionnaire. RESULTS: Patients had an average age of 52 years. They were more
likely to be post-menopausal and to have a raised body mass index (BMI) (average
BMI 29.6 kg/m2). All 17 patients had an ovarian mass larger than ten cm in
maximal diameter. Fourteen of the 17 cases were benign. Three patients were
diagnosed with early stage mucinous ovarian tumours of low malignant potential.
There were no malignancies. The procedure was associated with a high level of
patient satisfaction. CONCLUSION: Combined mini-laparotomy and laparoscopy to
resect ovarian masses > ten cm has potential benefits for patients in terms of
faster recovery, lower analgesia requirements, and improved cosmetic outcome.
Larger prospective studies are required to adequately assess complication rates,
quality of life, and long-term outcomes in those patients with ovarian tumours of
low malignant potential.
PMID- 29943918
TI - Does prophylactic bilateral salpingectomy during pelviscopic hysterectomy
increase perioperative morbidity?.
AB - : Purpose ofinvestigation: To compare the safety of additional salpingectomies in
patients undergoing laparoscopic hysterectomies for benign indication. MATERIALS
AND METHODS: The study was conducted in the Ortenau Klinikum Offenburg (Baden
Wirttemberg, Germany). Classical laparoscopic hysterectomies were performed
between 2010 and 2011 and a prophylactic salpingectomy was added thereafter. The
authors analysed the postoperative complications until 2013 according to the
Clavien-Dindo scale in performing a logistic regression model adjusted on
potential confounders. They also analysed other surgery outcomes such as
operative time, duration of the hospital stay, and the blood loss during the
surgery. RESULTS: Over 301 patients were retrieved from the records.
Postoperative complication rates were not different between the two groups (13.8%
versus 14.2 % patients, OR = 0.93 [0.47 - 1.84], p = 0.84). Other outcomes were
also not different. CONCLUSION: Prophylactic salpingectomy performed during a
laparoscopic hysterectomy for benign conditions seems to be' safe and
recommended. Prospective studies especially with respect to the magnitude of the
prophylactic effect are needed.
PMID- 29943919
TI - Treatment and outcome of Stage I Al squamous carcinoma of the cervix: a
clinicopathologic study of 346 cases.
AB - OBJECTIVE: To analyze the clinicopathologic feature of Stage I A I squamous
carcinoma of the cervix (SCC) and to explore the outcome of different surgical
methods. MATERIALS AND METHODS: Clinicopathological data of 346 cases with Stage
I Al SCC diagnosed between November 2nd, 1995 and December 31st, 2011 were
reviewed and analyzed. RESULTS: As major diagnostic method, 44.5% (154/346)
patients accepted cold knife conization (CKC), while 58.1% (201/346) patient took
total hysterectomy (TH) as their final surgical methods. The trend in treatment
methods from 1995 to 2011 revealed that increasing cases were treated with CKC,
modified radical hysterectomy (MRH) obviously reduced, while the proportion
treated by TH remained unchanged. Due to a small number of cases receiving
vaginal trachelectomy (VT) and radical trachelectomy (RT), the authors did not
find any obvious changes. PROGNOSIS: The overall recurrence rate was 1.2%
(4/346). The overall survival rates for CKC, VT, TH, MRH, and RT were 100%, 100%,
98.2%, 100%, and 100%, and the difference was not statistically significant (p =
0.819). The incidence rate of LVSI was 4.9% (17/346), the overall survival rates
for patients with LVSI and without LVSI were 99.3% and 93.3%, respectively, and
there was statistical difference between them (p = 0.003). Univariate analysis
showed that only LVSI was an important predictor for survival (p = 0.030).
CONCLUSIONS: the treatments for Stage I Al SCC are becoming more conservative,
and individualized therapy and more frequent surveillance should be administrated
to those patients with LVSI.
PMID- 29943920
TI - The effects of intraperitoneal chemotherapeutic agents on adhesion formation.
AB - PURPOSE: Intra-abdominal adhesions are a major complication of healing.
Furthermore these adhesions may cause morbidity and sometimes mortality for
patients, and also are a financial burden to the health system. MATERIALS AND
METHODS: Cecum abrasion was performed in all rats and solutions containing saline
to group 1, 5-fluorouracil to group 2, cisplatin to group 3, paclitaxel to the
group 4, and mitomycin-C were administered into the abdomen of the groups,
respectively. The intra-abdominal adhesions were scored after the macroscopic
evaluation. RESULTS: Among the chemotherapeutic drugs, paclitaxel significantly
increases occurring of intra-abdominal adhesions in comparison with the control
group and the other drugs according to the evaluation of scoring and statistical
studies. CONCLUSION: It is suggested to use the drugs which have a proven anti
adhesion feature or barriers to the patients who are going to be applied
intraperitoneal chemotherapy with paclitaxel.
PMID- 29943921
TI - The impact of conisation on pregnancy outcome.
AB - AIM: The objective of present study was to investigate whether conisation is
associated with adverse pregnancy outcomes in Flanders, Belgium. Therefore a
retrospective cohort study was conducted at the Antwerp University Hospital.
MATERIALS AND METHODS: The study was approved by the Ethical Committee and based
on a questionnaire as well as on medical records. Confounders, like smoking,
alcohol use, drug use, chronic illness, and gynaecological disorders during
pregnancy were all taken into account. A multiple logistic regression was
performed for an association between adverse pregnancy outcomes and confounders.
RESULTS: The study showed that there was association between conisation, low
birth weight, and caesarean section. After conisation there was a significantly
higher risk of 3.275 on a low birth weight. The risk of a caesarean section after
conisation was tripled. A gynaecological disorder during the pregnancy had a
significantly higher risk of delivering a child with a low birth weight and a
higher risk of a caesarean section. Smoking and a chronic illness gave a
significant higher risk of caesarean section. DISCUSSION: Conisation is easy to
perform and highly effective in the prevention of cervical cancer. Conisation has
a high morbidity, as it is associated with severe adverse pregnancy outcome. A
conisation should therefore only be performed on a true indication; otherwise it
will be the victim of its own success.
PMID- 29943922
TI - Ovarian metastases from colorectal cancer: prognostic role of prophylactic
oophorectomy. A single center experience.
AB - BACKGROUND: The incidence of ovarian metastases (OM) from colorectal cancer (CRC)
is uncommon but women with OM from CRC had poorer quality of life and decreased
survival. Mateials and Methods: The authors retrospectively categorized women
submitted to surgery for CRC from January 2004 to December 2012 considering
previous mono- or bilateral-oophorectomy, oophorectomy performed during
colorectal resection, and oophorectomy performed after surgery for CRC and its
cause. The analysis focused on two groups: women who underwent surgery for CRC
before menopause and after menopause. Survival outcome in terms of overall
survival (OS) and disease- free survival (DFS) were assessed and appearance of OM
was also evaluated. RESULTS: In postmenopausal women with CRC who underwent left
hemicolectomy or anterior resection of the rectum the incidence of OM was 4 %
with a statistical significance (p < 0.05). The mean OS of patients with
metachronous OM was 26 months and the patients' age ranged from 60 to 70 years.
CONCLUSION: The authors suggest prophylactic oophorectomy in postmenopausal women
with an age between 60 and 70 years with cancer of left colon or rectum; in these
patients there was an increased risk of metachronous OM with related decrease of
OS.
PMID- 29943923
TI - A survey of knowledge and awareness of Jordanian female university students of
human papillomavirus infection and its vaccine.
AB - OBJECTIVE: To assess the knowledge and awareness of Jordanian female university
students regarding human papillomavirus (HPV) infection and its vaccine.
MATERIALS AND METHODS: A self-administered, anonymous questionnaire was
distributed to 450 participants at Jordan University of Science and Technology
(JUST) in Jordan. The survey focused on three areas: knowledge and awareness of
HPV infection, knowledge of HPV vaccine, and source of information about HPV
infection and its vaccine. RESULTS: The survey response rate was 79.8%. Most of
the respondents (about 68%) have heard about HPV and knew that the HPV is a virus
in the genital area that is sexually transmitted, and 59% of them knew that
persistent infection with PV virus can cause precancerous/cancerous diseases in
the genital tract. Only 45% of the respondents have ever heard about HPV vaccine
and 37.8% of them knew that HPV vaccine is very effective in preventing HPV
infection and its related precancerous/cancerous diseases. Majority of the
respondents, 78.7 % and 73.5%, who knew about HPV and HPV vaccine, respectively,
had heard about it from healthcare providers. CONCLUSION: The study suggests that
more health education and information about the HPV characteristics and HPV
vaccine is needed for female university students.
PMID- 29943924
TI - Docetaxel and nab-paclitaxel are safe alternative options for patients with
gynecologic malignancies following hypersensitivity reaction to paclitaxel.
AB - Docetaxel and nab-paclitaxel are safe alternatives to paclitaxel after
hypersensitivity reaction occurs. There was no significant difference in overall
survival between those that had paclitaxel, docetaxel, and nab-paclitaxel.
PMID- 29943925
TI - Complications of laser conization versus loop electrosurgical excision procedure
in pre- and postmenopausal patients.
AB - : Purpose ofinvestigation: The aim of this retrospective study was to compare the
results and complications of laser conization and loop electrosurgical excision
procedure (LEEP), performed for cervical intraepithelial neoplasia (CIN) or
microinvasive carcinoma, between postmenopausal and premenopausal patients.
MATERIAL AND METHODS: This study recruited a total of 551 patients. In the laser
group (n = 405), there were 361 (89.1%) premenopausal and 44 (10.9%)
postmenopausal women. In the LEEP group (n = 146), there were 129 (88.4%)
premenopausal and 17 (11.6%) postmenopausal women. The factors investigated in
both groups were the length of the tissue cone removed and the presence of
positive endocervical cone margins, residual disease, and cervical stenosis.
RESULTS: In the laser group, the length of the tissue cone was significantly
longer in postmenopausal patients (17.9 +/-3.9 mm vs. 15.7 +/- 3.6mm; p = 0.002).
The rate of positive endocervical margins was significantly higher in
premenopausal patients (9.1% vs. 0%; p = 0.037). The rate of cervical stenosis
was significantly higher in postmenopausal patients (59.1% vs. 8.3%; p < 0.0001).
In the LEEP group, there were no differences in the length of the tissue cone
(premenopausal, 11.7 +/- 1.9 mm vs. postmenopausal, 11.4 +/- 2.7 mm; p = 0.12),
the rate of positive endocervical margins (24.0% vs. 17.6%), or the rate of
residual disease (13.2% vs. 17.6%). The rate of cervical stenosis was
significantly higher in postmenopausal patients (23.5% vs. 4.1%; p = 0.002);
however this rate was significantly lower than that seen in the laser group.
CONCLUSION: In postmenopausal patients, the rates of positive endocervical cone
margins and of residual disease were higher in the LEEP group; however, the rate
of cervical stenosis was higher in the laser group. Physicians should be aware of
the characteristics of the devices used for cervical conization in postmenopausal
women with CIN.
PMID- 29943926
TI - Malignant transformation of mature cystic teratoma of the ovary: 30-year
experience of a single tertiary care center.
AB - OBJECTIVE: To review the authors' experience with this rare disease and describe
their management modality and the outcome. MATERIAL AND METHODS: From January
1983 to December 2013, 13 patients with malignant transformation arising in
ovarian MCT were treated at the Division of Gynecologic Oncology in the
University of Manitoba. Demographic characteristics, symptoms, signs, stage, mode
of therapy, and results of follow-up were reviewed retrospectively. RESULTS:
Median age at diagnosis was 53 years (range 25-65). The most common presenting
symptom was a palpable mass in nine cases. Squamous cell carcinoma (SCC) was
found in 38% (five cases), adenocarcinoma in 15% (two cases), anaplastic
carcinoma in 8% (one case), and papillary thyroid carcinoma in 38% (five cases).
Eight cases were Stage I, two cases were Stage II, and three cases were Stage
III. All patients underwent surgery. Five patients received adjuvant treatment
with platinum-based chemotherapy + pelvic radiation. Four patients had recurrent
disease (two SCC and two adenocarcinoma). Three patients died of disease after
recurrence. The median follow up period of the entire patient population was 60
months, with a three-year overall survival of 76%. CONCLUSION: Malignant
transformation of MCT is large ovarian tumors that mainly occur in patients in
their fifth and sixth decades of life. They often present as incidental
pathologic findings after surgery for MCT. SCC has traditionally been the most
common pathology, however in the present series, the authors found that papillary
thyroid carcinoma was equally common. Platinum-based chemotherapy with pelvic
radiation in early stage (including Stage IA) and locally recurrent dis- ease
should be offered. Advanced stages and mucinous adenocarcinoma represent a poorer
prognosis despite adjuvant treatment. In patients with papillary thyroid
carcinoma, conservative surveillance in early stage and adjuvant total
thyroidectomy with radioactive iodine treatment in advanced stage disease appears
to be an effective treatment.
PMID- 29943927
TI - Clinical and epidemiological profile of women with breast cancer managed in a
public referral hospital in northeastern Brazil.
AB - AIM: To evaluate the clinical and epidemiological profile of women with breast
cancer, managed in the Breast Service at Hospital Get6lio Vargas (HGV). MATERIALS
AND METHODS: A descriptive, observational cross-sectional study, involving 174
breast cancer patients, managed at the Breast Service at HGV in Teresina, in the
northeast of Brazil, from May 2011 to June 2014. Epidemiological variables
included age group, age at menarche, age at first childbirth, and menopause. The
tumor characteristics studied were histological type, TNM classification, and
staging. The results were organized in distribution tables. RESULTS: Breast
carcinoma was more common in patients aged 60 and over, in multiparous women, and
in women who were menopausal before age 55. The most common histological type was
ductal invasive carcinoma T2N1MO (Stage IIB) in 83 (48%) women. CONCLUSION: The
current study shows that the majority of carcinomas were Stage II or advanced
tumors, with clinically positive axillary lymph node status and weak correlation
with reproductive risk factors.
PMID- 29943928
TI - A retrospective analysis of patients treated for gestational trophoblastic
diseases: a 4-year experience of a tertiary hospital.
AB - AIM: To study incidence, clinical outcome, and follow-up data of the gestational
trophoblastic disease (GTD) in patients diagnosed in the present Department.
MATERIALS AND METHODS: This study included the authors' retrospective clinical
records regarding the cases of GTD which were diagnosed and followed up between
January 2011 and January 2015. Patients' age, gravidity and parity, obstetric
history, subgroup of GTD, gestational weeks, management results, and pre-post
treatment beta-hCG levels was investigated and an incidence study was
constituted. RESULTS: Total of 56 GTD cases were hospitalized and clinical
records of 16,840 normal spontaneous deliveries were evaluated during the study
period. The incidence of GTD was 3.3/1,000 cases. After histopathological
examination, nine of 47 cases were partial molar pregnancy, whereas 38 cases were
complete moles. There were no choriocarcinoma and invasive moles. All cases were
treated with vacuum curettage without complication. CONCLUSION: The GTD incidence
in this clinic is high with a rate of 3.3/1,000 per pregnancy compared to Turkish
literature. High birth rates of our population may play a role in high incidence
results. Further investigation in this field is essential.
PMID- 29943929
TI - Metastatic mammary carcinoma despite histologically negative sentinel lymph
nodes: are there any indicators for estimating recurrence and metastasis rates?.
AB - OBJECTIVE: This study aimed to identify indicators for an increased frequency of
recurrent or metastatic disease in women with mammary carcinoma staged negative
for nodal involvement. MATERIALS AND METHODS: 202/270 patients (age: mean 57.5,
range 24-83 years) with histologically confirmed early stage mammary carcinoma
negative for metastasis to the sentinel lymph nodes (SLN) were observed with
respect to their clinical course for a mean period of 3.6 years following SLN
extirpation. RESULTS: Forty of 202 patients with negative SLN underwent
chemotherapy (38/188 in the recurrence-free group vs. 2/14 in the group with
progressive disease) and 79% of both subcollectives did not undergo chemotherapy.
Seven of 188 of patients in the recurrence-free group received immunotherapy and
none of the patients in the group with disease progression were treated with this
modality. One hundred sixty-two of 202 patients with negative SLN underwent
hormone therapy, 157/188 in the recurrence-free group and 5/14 in the group with
disease progression. One hundred sixty-four of 202 patients with negative nodal
status received adjuvant radiation therapy of the affected breast, 156/188 in the
recurrence-free group and 8/14 in the group with disease progression.
CONCLUSIONS: When assessing the risk profile for disease recurrence or the
occurrence of metastatic disease, statistically significant differences with
respect to disease progression were identified for the parameters chemo-,
antibody, hormone, and radiation therapy. The preliminary observations of this
study show that even those patients in an early disease stage and with negative
SLNs profit from these adjuvant non-surgical therapy options.
PMID- 29943930
TI - Endometrial malignancies arising on endometrial polyps and precursor lesions.
AB - INTRODUCTION: Polyps are covered with endometrial epithelium and composed of
varying proportions of gland, stroma, and blood vessels. Traditionally,
endometrial polyps are accepted as a precursor of cancer. The aim of this study
was to evaluate the relationship between malignancies arising on endometrial
polyps and precursor lesions of these malignancies. MATERIALS AND METHODS: Data
of patients who underwent total abdominal hysterectomy because of a malignancy
diagnosed on endometrial polyps were obtained retrospectively from pathology
archives. RESULTS: When all malignancies on endometrial polyp were considered,
37% of cases were Type I, 55% were Type II, and 7% were carcinosarcoma.
Endometrial intraepithelial carcinoma (EIC) was detected as tumor-adjacent areas
on the polyp in eight of the patients who were diagnosed with serous carcinoma.
CONCLUSION: The authors found a precursor lesion in 20 (74%) of their patients
who showed endometrial malignancy developing on endometrial polyps. Even when an
overt malignancy is not detected on polyps in the curettage material, precursor
lesions should be carefully searched.
PMID- 29943931
TI - The effect of aprepitant and dexamethasone combination on paclitaxel-induced
hypersensitivity reaction.
AB - PURPOSE OF INVESTIGATION: Dexamethasone (DEX) is often administered to prevent
paclitaxel (PTX)-induced hypersensitivity reactions (HSR). The DEX dose is
reduced when administered in combination with aprepitant (APR). However, the
influence of that dose reduction on PTX-induced HSR has not been thoroughly
studied. The present authors aimed to investigate the effects of the combined
administration of APR and DEX on PTX-induced HSR. MATERIALS AND METHODS: Fifty
one patients who received a three-week PTX regimen in combination with APR and
DEX were retrospectively analysed. The authors compared the dose of DEX with the
incidence of HSR and other toxicities. RESULTS: Patients were stratified into two
groups depending on the DEX dose, > 20 mg (group D, 33 patients), and < 12 mg
(group reD, 26 patients). The incidence of HSR in Groups D and reD were 51.5%
(17/33) and 53.8% (14/26), respectively. The frequencies of other toxicities
between the groups were comparable. CONCLUSION: The findings suggest that
although a reduction in DEX dose is possible when APR is co-administered, this
does not affect the PTX-induced HSR. However, adverse effect should be closely
monitored.
PMID- 29943932
TI - Attitudes and knowledge among parents or guardians of 12-year-old girls about HPV
vaccination - A population-based survey in Iceland.
AB - PURPOSE: To assess attitude and knowledge among parents or guardians of 12-year
old girls about human papillomavirus (HPV), cervical cancer, and HPV vaccination.
Material andMethods: A mail survey was sent to a randomized sample of 1,000
parents or guardians of 12-year-old girls from a cohort of total 2,092 girls born
in 1995 and registered in the Icelandic National Register by the end of December
2007. RESULTS: Of the 994 eligible parents, 583 (59%) returned the questionnaire.
Majority of the respondents were mothers who had two or three children. More than
one-third of respondents had university education and 84% were married or living
with a partner. Over two-thirds did not know that HPV causes cervical cancer and
genital warts. Almost all (> 90%) would vaccinate theirs daughters with a HPV
vaccine, 73% said they would vaccinate their sons, or themselves if the vaccine
was effective for them. Only 11% believed HPV vaccination would increase
promiscuity or decrease cervical screening attendance. CONCLUSION: In Iceland,
willingness to vaccinate young girls with HPV vaccine is high, however, knowledge
about HPV infections is limited.
PMID- 29943933
TI - Diagnostic value of transvaginal color Doppler ultrasound on endometrial lesions.
AB - OBJECTIVE: To discuss the diagnostic value of transvaginal color Doppler
ultrasound on endometrial lesions. MATERIALS AND METHODS: The study included 126
cases diagnosed with endometrial lesions by transvaginal color Doppler ultrasound
that were examined by hysteroscopy, biopsy, and curettage pathology, and compared
with pathology. RESULTS: The transvaginal color Doppler ultrasound diagnosis
corresponded to 92.6% (117 of 126 cases) of the pathology diagnosis. CONCLUSIONS:
Transvaginal color Doppler ultrasound has important diagnostic value in the case
of endometrial lesions, has a high rate of detection and diagnostic on
endometrial lesions, and is the best method for diagnosis of endometrial lesions.
PMID- 29943934
TI - The ovarian cancers in geriatric population: the validity of inflammatory
markers, malignancy risk indices 1, 2, 3, 4, and CA-125 levels in malignancy
discrimination of adnexal masses.
AB - PURPOSE: To investigate the predictive value of the Risk of Malignancy Index
(RMI), CA-125, and inflammatory markers in discriminating ovarian cancers (OCs).
MATERIALS AND METHODS: The postmenopausal (PM) women (n= 139) with adnexal masses
who un- derwent surgery were included. The predictive value of CA-125, RMI (1,
2,3, and 4) and inflammatory markers [neutrophil lymphocyte ratio (NLR), platelet
lymphocyte ratio (PLR)] were calculated in geriatric (G) and non-geriatric women.
RESULTS: OCs had significantly increased NLR and PLR. RMI models were highly
reliable in PM (Kappa: 0.642-0.715; AUC: 0.907-0.934). CA-125 measurement alone
had good accuracy and moderate reliability in PM (kappa: 0.507-0.587), excellent
accuracy and moderate reliability in G, NLR, and PLR predicting OCs, showed fair
agreement in the PM, while PLR had a moderate agreement with G. CONCLUSION: RMI
algorithms were the best models for malignancy prediction. However, the rise of
PLR and CA-125 levels in a G population may be used as refer- ring adnexal masses
to gynecologic oncologists.
PMID- 29943935
TI - The expression and significance of WT1 in xenotransplanted ovarian carcinoma
treated by paclitaxel.
AB - In this study, the authors investigated the expression and significance of WTl in
xenotransplanted ovarian carcinoma cell SKOV3 of nude mice treated with
paclitaxel. Xenotransplanted ovarian carcinoma was established in nude mice using
the SKOV3 cell line. The mice were randomized into the treatment group with
paclitaxel and control group with normal sodium. The sizes of the
xenotransplanted tumors were measured and the tumor specimens were confirmed by
routine hemotoxylin-eosin (H&E) staining. The apoptosis index was then assayed
using flow cytometry. WTl and bcl-2 expression were detected with
immunohistochemistry, and WT1 mRNA expression was determined by reverse
transcriptase polymerase chain reaction (RT-PCR). The authors found that the
growth of the xenotransplanted tumor was inhibited by paclitaxel therapy.
Compared to the control group, the apoptosis rate was significantly increased in
the treatment group (p < 0.05). At the same time, the expression of WTl, bcl-2
and WTI, mRNA were significantly decreased in the paclitaxel therapy group (p <
0.05). The authors conclude that the WTl gene may play an important role during
apoptosis of ovarian carcinoma and the mechanism may be closely related to bcl-2.
PMID- 29943936
TI - Endometrioid adenocarcinoma arising from adenomyosis: a case report.
AB - BACKGROUND: Endometriosis is most commonly found in the peritoneum of the lesser
pelvis and in the genital tract (in the ovaries). Its malignant transformation is
quite rare, which usually appears in patients who previously underwent surgical
procedures aimed at treating endometriosis. Years of hormone substitution
(unopposed estrogen therapy) is also considered to have a role. According to the
present authors' current knowledge, these are mostly well-differentiated tumors
with low malignancy, which are primarily treated surgically. CASE: In the present
case the authors present a 73-year-old female patient who underwent a laparotomy
due to abdominal pain and a mass in the lesser pelvis. The authors performed
hysterectomy along with bilateral adnexectomy and omental resection. The
histological examination of the specimens verified an endometrial adenocarcinoma
formed on the ground of adenomyosis and the endometrial adenocarcinoma of the
left ovary. CONCLUSION: The malignant transformation of endometriosis is rare,
and the mechanisms how it develops on the grounds of adenomyosis is currently
unclear.
PMID- 29943937
TI - Total vaginectomy and radical vulvectomy for extension of extra-mammary Paget's
disease.
AB - Extra-mammary Paget's disease of the vulva is a rare non-invasive adenocarcinoma
that usually occurs in postmenopausal women. Histologically, it often extends
beyond the visible lesion, leading to positive surgical margins and frequent
recurrences, but can be managed by simple vulvectomy or wide local excision.
Although current evidence supports the use of radical surgery as an alternative
to the generally performed wide local excision in the treatment of widely
extended extra mammary Paget's disease of the vulva, nonetheless there
controversy still exists regarding the extent of an adequate resection margin.
Here the authors present a case of successful radical vulvectomy with total
vaginectomy without adjuvant treatment on a delayed diagnosis of extra-mammary
Paget's disease, extending from the vulva to the apex of vagina.
PMID- 29943938
TI - A mixed carcinoma of the uterus arising from an atypical polypoid adenomyoma: a
case report.
AB - An atypical polypoid adenomyoma (APAM) is a benign mixed epithelial and
mesenchymal uterine tumor. Patients typically present with hypermenorrhea or
abnormal uterine bleeding, and the tumor is most commonly found in nulliparous or
infertile women of reproductive age. The natural pathological course of an APAM
remains unclear because of the rarity of the disease. The coexistence or
sequential development of low-grade malignant endometrial tumors has been
reported; however, reports of a mixed carcinoma arising from an APAM have not
been published yet. In this report, the authors describe the case of a woman with
a mixed carcinoma of the uterus arising from an APAM. This case extends our
knowledge of the natural pathological course of an APAM and its etiological
relationship with a mixed carcinoma of the uterus, which may contribute to the
development of management strategies for an APAM.
PMID- 29943939
TI - Ovarian endometrioid carcinoma with yolk sac tumor component in a postmenopausal
woman.
AB - Yolk sac tumor (YST) coexisting with a variety of histologic patterns have been
described, but with an epithelial malignant component is extremely rare. It has
been suggested that this rare tumor represents an adenocarcinoma with aberrant
differentiation because it occurs in the same age range as epithelial ovarian
carcinoma and shows an aggressive behavior and poor prognosis. Although
chemotherapy is effective for pure YST, YST with endometrioid adenocarcinoma does
not respond to chemotherapy. Here the authors report a postmenopousal women with
ovarian endometrioid adenocarcinoma (OEC) associated with YST.
PMID- 29943940
TI - Myxoid leiomyosarcoma of the uterus: a case report and review of the literature.
AB - A para 1, 52-year-old female was admitted with complaints of irregular vaginal
bleeding for the previous six months. Ultrasonography revealed a 4x6-cm tumor
extending into the uterine cavity and cervical canal. On vaginal examination, a
2x2-cm tumor protruding from the cervical os was found, and an enlarged uterus
was palpated. Vaginal intrauterine tumor resection was performed, and the patient
was diagnosed with uterine myxoid leiomyosarcoma. A total abdominal hysterectomy
with bilateral salpingo-oophorectomy was performed, followed by postoperative
chemotherapy. Twenty-one months after surgery, the patient died of tumor
recurrence. Uterine myxoid leiomyosarcoma is an extremely rare variant of uterine
sarcoma with a poor prognosis and malignant biological behavior.
PMID- 29943941
TI - Incidental tubal endometrioid adenocarcinoma - case report.
AB - The fallopian tubes represent a highly important structure for ovarian
carcinogenesis. They provide the passage of eutopic endometrium from the uterus,
as well as metastatic cells from the ovaries. A direct source of tumor cells for
ovarian cancer was also recently confirmed in the fallopian tubes. The authors
present a case report of an incidental tubal endometrioid carcinoma with the
coexistence of adenomyosis.
PMID- 29943942
TI - Rapid enlargement of endometrial stromal sarcoma after uterine fibroid
embolization for presumed adenomyosis: a case report and literature review.
AB - Uterine sarcomas have rarely been diagnosed after uterine artery embolization. It
remains unclear whether the diagnostic work-up is required prior to such
embolization to prevent a missed diagnosis of sarcomas and a delay in providing
definitive treatment. Because of the rarity and heterogeneity of endometrial
stromal neoplasms, little is known about their epidemiology, pathogenesis, and
molecular pathology. The authors report a case of low-grade endometrial stromal
sarcoma (ESS) diagnosed after uterine fibroid embolization. Although they
performed laparoscopic biopsy of the rapidly growing uterine mass, they could not
detect the ESS. Although rare, ESS should be considered in the differential
diagnosis of uterine fibroid enlargement. It is essential to assess the risk of
malignancy by taking into account the patient's clinical symptoms, results of the
physical exam, and imaging findings prior to uterine artery embolization.
Pathologic diagnosis should include an adequate biopsy sample and the use of
molecular genetic testing.
PMID- 29943943
TI - Obturator mononeuropathy due to adenocarcinoma of unknown primary origin.
AB - A 35-year-old woman presented with a three-month history of left groin and thigh
pain. Neurological examination and electromyography showed pathological features
consistent with obturator nerve involvement. Imaging studies revealed a left
retroperitoneal mass, which by pathological examination was shown to be
metastatic adenocarcinoma of possible Mullerian origin. Primary tumor could not
be detected in a follow-up period of three years. Obturator mononeuropathy can be
the first manifestation of cancer. Cancer of unknown primary origin may
occasionally be local, well-restricted and carry a good prognosis.
PMID- 29943944
TI - An exploration of the reasons why people attend but do not wait to be seen in
emergency departments.
AB - AIM: The aim of the study was to explore the reasons why people do not always
wait to receive treatment after registering in emergency departments (EDs).
METHOD: Patients who attended the ED at a general hospital in the south of
England and left without being seen (LWBS) were recorded between 1 June and 31
August 2016 and 597 patient records were analysed. Six patients participated in
semi-structured interviews. Data were manually coded. FINDINGS: The most common
presenting complaint for people who LWBS was limb problems, however some had
potentially more serious conditions such as chest pain. The six interviewees
accessed the ED because of a perceived urgent need, and reasons for leaving
before being seen included long waiting time, other commitments, non-availability
of specialty services, perceiving their problem as less urgent, resolution of
condition and discomfort in the waiting area. CONCLUSION: People who LWBS may not
have trivial health problems, which is a risk for them and hospital trusts.
Although many of the people who LWBS did so because of the lengthy waiting time,
there may be other factors involved some of which could be prevented.
PMID- 29943945
TI - Evolution of gold nanoparticle clusters in living cells studied by sectional dark
field optical microscopy and chromatic analysis.
AB - The evolution of gold nanoparticle (Au NP) clusters in living cells are studied
by using sectional dark-field optical microscopy and chromatic analysis approach.
During endocytosis, Au NP clusters undergo fantastic color changes, from green to
yellow-orange due to the plasmonic coupling effect. Analysis of brightness/hue
values of the dark-field images helps estimate the numbers of Au NPs in the
clusters. The Au NP clusters were further categorized into four groups within the
endocytosis. As the results, the late endosomes had increased number of large Au
NP clusters with time, while clustered numbers in secondary and tertiary groups
were first increased and then decreased due to the fusion and fission of the
endocytic vesicles. The time constants and cluster numbers for different groups
are fitted by using an integrated rate equation, and show a positive correlation
with the size of the Au NP cluster. The efficiency of Au NP uptake is only about
50% for normal cells, while 75% for cancer cells. Compared to normal cells,
cancer cells show a larger number in uptake, while faster rate in removal. The
propose method helps the kinetic study of endocytosed nanoparticles in
physiological conditions.
PMID- 29943946
TI - Healing of human critical-size alveolar bone defects secondary to cyst
enucleation: a randomized pilot study with 12 months follow-up.
AB - BACKGROUND: Alveolar bone cyst enucleation can give rise to critical-size defects
whose healing may be incomplete due to the loss of periosteum or bone walls and
there is a paucity of studies investigating the use of immediate bone grafts. The
aim of this study was to compare spontaneous healing versus a deproteinized
bovine bone graft. METHODS: In this prospective randomized clinical pilot study,
twenty patients requiring the removal of a cyst >=20 mm in maximum diameter were
randomly assigned to one of two groups: deproteinized bovine bone grafting (test)
or spontaneous healing (control). Computed tomographies were obtained
preoperatively and 12 months after surgery and the radiolucent volumes were
compared. Residual radiological morphology and clinical outcomes at 7 days and 1,
6 and 12 months after surgery were also assessed. RESULTS: The median percentage
reduction in the volume of the defect was 98% in the test group and 73% in the
control group (P=0.001) with an evidence of soft tissue invagination in the
latter. There were no differences in the clinical parameters between the two
groups. CONCLUSIONS: Within the limitations of this pilot study, the healing of
critical-size alveolar bone defects is incomplete at 1 year observation and the
use of deproteinized bovine bone graft did not influence the clinical outcomes.
PMID- 29943947
TI - Evaluation of stress biomarkers and electrolytes in saliva of patients undergoing
fixed orthodontic treatment.
AB - BACKGROUND: The aim of this study was to test the hypothesis that treatment with
orthodontic appliances evokes significant functional limitations and emotional
stress, which can be detected by salivary biomarkers. METHODS: Twenty subjects
(10 men and 10 women) who underwent orthodontic treatment were included in this
prospective study. Saliva was sampled for detection of alpha-amylase activity and
cortisol levels at three different times: before bracket placement (T0), 24 hours
after archwire placement (T1), and 30 days after archwire placement (T2). The
saliva electrolytes concentrations of calcium, phosphorus, magnesium, sodium and
potassium were also evaluated. Moreover, the possible functional limitations of
the appliances were evaluated by a masticatory performance test and pain
experience registration. All variables were compared with those in a control
group with normal occlusion. RESULTS: The orthodontic patients exhibited a
significant increase in emotional stress as detected by the alpha-amylase
activity at T1, the period in which patients reported the higher values of pain
and exhibited the lower masticatory performance indices. The basal salivary
cortisol was not affect by the treatment and the main change detected in
electrolyte concentration was a sodium reduction, when these patients were
compared to controls. CONCLUSIONS: The present data indicate that orthodontic
patients are under emotional stress only during the period of higher pain
experience, which could also disrupt the masticatory performance. However, these
alterations were not correlated with a single measurement of stress-related
biomarkers in saliva, suggesting that these solitary endocrine measurements are
not adequate to predict the temporary pain and masticatory limitation
experimented by patients undergoing orthodontic treatment.
PMID- 29943948
TI - Fluorescent characterization of amyloid deposits in the kidneys of mdx mice.
AB - Amyloidosis is a group of diseases that occurs when amyloid proteins are
deposited in tissues and organs. The traditional way of identifying amyloid in
tissue sections is staining with Congo red. However, this method has a number of
limitations including background staining (background fluorescence), low
fluorescence intensity and false-positive staining. Therefore, a complex of
fluorescence-based methods should be applied to characterize tissue localization
of amyloid deposits. The aim of this study was to identify amyloid deposits in
the kidneys of dystrophin-deficient mdx mice using different fluorescent dyes. We
examined 8 cases of renal amyloidosis in aged mdx mice. In all cases, we used
traditional methods for amyloid detection (Congo red and Thioflavin T), as well
as a new fluorescent dye, disodium salt of 2,7- (1-amino-4-sulfo-2-naphthylazo)
fluorene (DSNAF). In our study, we confirmed the amyloid structure of protein
deposits in kidneys of aging mdx mice by several fluorescence-based staining
methods. We found that fixation method has profound effects on downstream
staining procedures, and demonstrated that the application of specific fixative,
zinc-ethanol-formaldehyde (ZEF), instead of traditional NBF allow to reduce the
background fluorescence. We also illustrated the usefulness of novel fluorescent
dye DSNAF for detection of amyloid deposits in mouse tissues. Our results
confirmed the strong affinity and high specificity of this dye for amyloid
fibrils. The verification of DSNAF for detecting amyloid in human tissues will
provide a conclusion on the applicability of the developed staining method in
clinical research practice.
PMID- 29943949
TI - Marine bisindole alkaloid: A potential apoptotic inducer in human cancer cells.
AB - Marine organisms such as corals, sponges and tunicates produce active molecules
which could represent a valid starting point for new drug development processes.
Among the various structural classes, the attention has been focused on 2,2-bis(6
bromo-3-indolyl) ethylamine, a marine alkaloid which showed a good anticancer
activity against several tumor cell lines. Here, for the first time, the
mechanisms of action of 2,2-bis(6-bromo-3-indolyl) ethylamine have been evaluated
in a U937 tumor cell model. Morpho-functional and molecular analyses,
highlighting its preferred signaling pathway, demonstrated that apoptosis is the
major death response induced by this marine compund. Chromatin condensation,
micronuclei formation, blebbing and in situ DNA fragmentation, occurring through
caspase activation (extrinsic and intrinsic pathways), were observed. In
particular, the bisindole alkaloid induces a mitochondrial involvement in
apoptosis machinery activation with Blc-2/Bcl-x down-regulation and Bax up
regulation. These findings demonstrated that 2,2-bis(6-bromo-3-indolyl)
ethylamine alkaloid-induced apoptosis is regulated by the Bcl-2 protein family
upstream of caspase activation.
PMID- 29943950
TI - Diagnosis of sudden cardiac death due to early myocardial ischemia: An
ultrastructural and immunohistochemical study.
AB - The aim of this post-mortem ultrastructural and immunohistochemical study is to
explore the characteristics of acute myocardial ischemia in the context of sudden
death, using the combination of two different methods, both more insightful than
ordinary histology. Transmission electron microscope and immunohistochemistry, in
addition to the traditional histology, were applied to study human heart
specimens collected during forensic autopsies. The whole series was sub-grouped
into cases (n=17) and controls (n=10). The control group consisted of unnatural
death with a short agonal period (immediately lethal injuries). Heart samples of
the two cohorts of subjects were prepared for electron microscopy. On the other
hand, each specimen, formalin fixed and paraffin embedded, was stained with
haematoxylin and eosin and immunoreacted with the following primary antibodies:
antiFibronectin, antiConnexin-43, anti npCx43 (dephosphorylated form of
Connexin43), antiZonula occludens-1. Immunopositivity of each marker in the
myocardium was semi-quantitatively graded. Electron microscopy revealed a number
of interesting differences between acute myocardial ischemia and controls,
regarding the morphology of nucleus, mitochondria and intercellular junctions. By
immunohistochemistry, fibronectin was found to be markedly increased in the
extracellular matrix of the acute myocardial ischemia cases, with a remarkable
difference in respect of controls. Connexin 43 staining disclosed a slightly
increase in the cytoplasm of acute myocardial ischemia cases with respect to the
controls, whereas no relevant differences were seen between cases and controls at
intercellular junctions. Dephosphorylated form of Cx43 showed an evident
difference of staining in cases compared to controls and overall this difference
more evident in the cytoplasm. Zonula occludens 1, described as an important
marker for functional modification of cardiac muscle fibers, resulted negative or
very weak in the vast majority of both cases and controls. The present study
attempts to simultaneously apply electron microscopy and immunohistochemistry, in
order to figure out the morphological changes that might lead to pathological
processes underlying the sudden, unexpected death due to acute myocardial
ischemia, and consequently to find useful diagnostic markers of very early
ischemic injury. Both methods showed significant differences between acute
myocardial ischemia and controls, regarding, overall nuclei, mitochondria, and
intercellular junctions.A.
PMID- 29943951
TI - Autophagic processes increase during senescence in cultured sheep neurons and
astrocytes.
AB - A possible response to aging is autophagy, a self-digestion process in which
portions of cytoplasm are encapsulated by double-membrane-bound structures and
delivered to lysosome for degradation. A previous work of our group showed that
astrocytes under starving conditions are characterized by a higher upregulation
of the marker of autophagy LC3 II than neurons. Aim of the present work was to
evaluate LC3 II expression in an aging model consisting in fetal sheep neurons
and astrocytes at 10, 20 and 30 days of culture. Such model has been validated by
a remarkable activity of beta-galactosidase, commonly used to reveal cell aging.
LC3 II immunoreactivity in neurons and astrocytes progressively increased with
time but differences were observed on the basis of cell density. Indeed, LC3 II
immunoreactivity is higher in clusters of neurons and astrocytes and this may be
due to the fact that cell-cell contact would represent a second stress in
addition to aging itself. Both cell types displayed a reduction in LC3 II signal
in nuclei, and a corresponding strengthening in the cytoplasm with time. This may
be due to the need of aged cells to remove damaged cytoplasmic components through
autophagic processes. Such variation in LC3 II localization could be caused by
migration from the nucleus to cytoplasm as well as possible de novo
intracytoplasmic production. The present work based on sheep neural cells in
vitro may represent a helpful tool in the studies on aging processes in which
autophagy plays a remarkable role.
PMID- 29943952
TI - Quantification of placental change in mouse models of preeclampsia using magnetic
resonance microscopy.
AB - Abnormal development of the placenta is postulated to be central to the aetiology
of preeclampsia. This study investigates changes in placental histopathology in
mouse models of preeclampsia compared to the morphology using magnetic resonance
microscopy (MRM) (11.7 T) of intact ex vivo tissue followed by 3D analysis of the
image data. Here, C57BL/6JArc pregnant mice were subject to either normal
pregnancy (n=3), or to one of two experimental models of preeclampsia; TNF-alpha
infusion (n=3) or reduced uterine perfusion pressure(RUPP) (n=3). Placental
tissue was collected at gestational day (gd) 17, fixed in formalin and incubated
with MagnavistTM contrast agent, and high resolution images (50 MUm * 50 MUm * 50
MUm voxels) obtained by magnetic resonance imaging at 11.74 T. Visual
segmentation into placental subregions and three dimensional (3D) reconstruction
followed by volume analysis was performed with AmiraTM 3D analysis software. The
significance of differences between treatment groups in total and regional
volumes was assessed. In a single placenta the volumes measure by standard
histology were compared. Three placentas from each animal were imaged, segmented
into anatomical regions and 3D reconstructions generated. Total placental volume,
labyrinth and decidual volume were not significantly different between groups.
The junctional zone volume was found to be significantly larger in the RUPP
animals (18.5+/-1.5 mm3) compared to TNF-alpha infused animals (15.8+/-1.5) or
control animals (15.0+/-0.7, P<0.01). However, the decidual/junctional zone
volume was smaller in the TNF-a compared to control animals (P<0.05). Placental
structural change in experimental models of preeclampsia is able to be visualized
and quantified using MRM and 3-D analysis. These techniques could prove to be a
powerful tool in examining changes in placental morphology.
PMID- 29943953
TI - Distribution of non-myelinating Schwann cells and their associations with
leukocytes in mouse spleen revealed by immunofluorescence staining.
AB - The nervous system and the immune system communicate extensively with each other
in order to maintain homeostasis and to regulate the immune response. The
peripheral nervous system (PNS) communicates specifically with the immune system
according to local interactions, including the "hardwiring" of
sympathetic/parasympathetic (efferent) and sensory nerves (afferent) to lymphoid
tissue and organs. To reveal this type of bidirectional neuroimmune interaction
at the microscopic level, we used immunofluorescent staining of glial fibrillary
acidic protein (GFAP) coupled with confocal microscopy/3D reconstruction to
reveal the distribution of non-myelinating Schwann cells (NMSCs) and their
interactions with immune cells inside mouse spleen. Our results demonstrate i)
the presence of an extensive network of NMSC processes in all splenic
compartments including the splenic nodules, periarteriolar lymphoid sheath
(PALS), marginal zone, trabecula, and red pulp; ii) the close association of
NMSC processes with blood vessels (including central artries and their branches,
marginal sinuses, penicillar arterioles and splenic sinuses); iii) the close
"synapse-like" interaction/association of NMSC processes with various subsets of
dendritic cells (DCs; e.g., CD4+CD11c+ DCs, B220+CD11c+ DCs, and F4/80+ CD11c+
DCs), macrophages (F4/80+), and lymphocytes (B cells, CD4+ T helper cells). Our
novel findings concerning the distribution of NMSCs and NMSC-leukocytes
interactions inside mouse spleen should improve our understanding of the
mechanisms through which the PNS affects cellular- and humoral-mediated immune
responses in a variety of health conditions and infectious/non-infectious
diseases.
PMID- 29943954
TI - ATP metabolizing enzymes ENPP1, 2 and 3 are localized in sensory neurons of rat
dorsal root ganglion.
AB - In dorsal root ganglion (DRG) neurons, ATP is an important neurotransmitter in
nociceptive signaling through P2 receptors (P2Rs) such as P2X2/3R, and adenosine
is also involved in anti-nociceptive signaling through adenosine A1R. Thus, the
clearance system for adenine nucleotide/nucleoside plays a critical role in
regulation of nociceptive signaling, but there is little information on it,
especially ectoenzyme expression profiles in DRG. In this study, we examined
expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterases
(ENPPs), by which ATP is metabolized to AMP, in rat DRG. The mRNA expression
levels of ENPP2 were greater than those of ENPP1 and ENPP3 in rat DRGs. On
immunohistochemical analysis, ENPP1, 2 and 3 were found in soma of DRG neurons.
Immunopositive rate of ENPP3 was greater than that of ENPP1 and ENPP2 in all DRG
neurons. ENPP3, as compared with ENPP1 and ENPP2, was expressed mainly by
isolectin B4-positive cells, and slightly by neurofilament 200-positive ones. In
this way, the expression profile of ENPP1, 2 and 3 was different in DRGs, and
they were mainly expressed in small/medium-sized DRG neurons. Moreover, ENPP1-, 2
and 3-immunoreactivities were colocalized with P2X2R, P2X3R and prostatic acid
phosphatase (PAP), as an ectoenzyme for metabolism from AMP to adenosine.
Additionally, PAP-immunoreactivity was colocalized with equilibrative nucleoside
transporter (ENT) 1, as an adenosine uptake system. These results suggest that
the clearance system consisted of ENPPs, PAP and ENT1 plays an important role in
regulation of nociceptive signaling in sensory neurons.
PMID- 29943955
TI - The role of mutated SOD1 gene in synaptic stripping and MHC class I expression
following nerve axotomy in ALS murine model.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
characterized by motoneuron death. Several cellular pathways have been described
to be involved in ALS pathogenesis; however, the involvement of presynaptic
stripping and the related MHC class I molecules in mutant SOD1 motoneurons
remains to be clarified. To this purpose, we here investigated, for the first
time, the motoneurons behavior, di per seand after facial axonal injury, in terms
of synaptic stripping and MHC class I expression in wild-type (Wt) mice and in a
murine model of ALS, the SOD1(G93A) mice, at the presymptomatic and symptomatic
stage of the disease. Concerning Wt animals, we found a reduction in
synaptophysin immunoreactivity and an increase of MHC class I molecules in facial
motoneurons after axotomy. In uninjured motoneurons of SOD1(G93A) mice, an
altered presynaptic framework was evident, and this phenomenon increased during
the disease course. The alteration in the presynaptic input is related to
excitatory fibers. Moreover, after injury, a further decrease of excitatory input
was not associated to an upregulation of MHC class I molecules in motoneuron
soma. This study demonstrates, for the first time, that the presence of mutated
SOD1 protein affects the MHC class I molecules expression, altering the
presynaptic input in motoneurons. Nevertheless, a positive MHC class I
immunolabeling was evident in glial cells around facial injured motoneurons,
underlying an involvement of these cells in synaptic stripping. This study
contributes to better understand the involvement of the mutated SOD1 protein in
the vulnerability of motoneurons after damage.
PMID- 29943956
TI - Appearance of beta-dystroglycan precedes the formation of glio-vascular end-feet
in developing rat brain.
AB - Dystroglycan has an important role in binding of perivascular glial end-feet
tothe basal lamina. Its beta-subunit is localized in the glial end-feet. The
investigation period lasted from E(embryonic day)12 to E20. Laminin and beta
dystroglycan were detected by immunohistochemistry, the glial localization of the
latter one was supported by electron microscopy. The immatureglial structures
were visualized by the immunostaining of nestin. The beta-dystroglycan
immunoreactivity appeared at E16 following the laminin of basal lamina but
preceding the perivascular processes of radial glia (E18) and astrocyte-like
cells (E20). It occurred in cell bodies which attached to the vessels directly
but not with vascular processes and end-feet. The presence of beta-dystroglycan
in such immature cells may promote their differentiation to perivascular
astrocytes and influence the formation of the glio-vascular processes.
PMID- 29943958
TI - Aortic treatment in connective tissue disease.
AB - Connective Tissue Disease (CTD) represents a group of genetic conditions
characterized by disruptive matrix remodeling. When this process involves aortic
and vascular wall, patients with CTD have a high risk of developing arterial
aneurysms, dissections and ruptures. Open surgical repair is still the gold
standard therapy for patients with CTD with reasonable morbidity and mortality
risk. The surgical treatment of CTD often requires multiple operations. In the
endovascular era, fenestrated and branched stent grafts may play a role in
reducing the complications of multiple open operations. Although the long-term
results of endovascular treatment in the setting of CTD are unknown, it is
generally accepted that endovascular treatment is restricted to selected patients
with high surgical risk. In an emergency setting, endovascular intervention can
serve as a lifesaving bridge to elective open aortic repair. Aortic centers
performing a large volume of complex open and endovascular aortic repairs have
started to combine these 2 techniques in a staged fashion. The goal is to reduce
the morbidity and mortality associated with extensive aortic repairs in CTD
patients. For this reason, recommend endovascular therapy when a "graft to graft"
approach is possible. In this scenario, the surgeon who performs the open repair
must take into consideration future interventions. Surgical repair in any aortic
segment should allow creation of proximal and distal landing zones over 4 cm to
secure the sealing of a future stent graft. Connective tissue disease should be
treated with a multidisciplinary approach, in high volume centers. Endovascular
treatment represents a potential option in patients at high risk for open repair.
Staged hybrid procedures have emerged as a way to reduce spinal cord ischemia and
avoid multiple open surgeries. The aim of this article is to discuss the
management of aortic diseases in CTD, focusing on to the role of standard open
surgery and emerging endovascular treatment, and to give an overview of the few
series published regarding this topic with a small number of patients.
PMID- 29943957
TI - GalNAc-T15 in gastric adenocarcinoma: Characterization according to tissue
architecture and cellular location.
AB - Gastric cancer (GC) is the second most common cause of cancer-related deaths in
the world. This study aims to investigate the differential tissue expression of
ppGalNAc-T15 and to evaluate its possible association with clinical-pathological
parameters and outcome of gastric adenocarcinoma patients. For these 70 patients
were evaluated the expression by immunohistochemistry to ppGalNAc-T15. Our
results showed that 33 (47.1%) patients were ppGalNAC-T15+ positive and 37
(52.9%) negative. Positive staining for ppGalNAc-T15 was significantly present in
patients older than 60 years (P=0.0306) and submitted to total gastrectomy
(P=0.0087). Also, some results remained at the limit of significance as surgical
standing (P=0.0562) and histological grade (P=0.0549). Therefore, the ppGalNAc
T15 immunoreactivity can be useful to understand the prognosis of patients with
gastric cancer.
PMID- 29943959
TI - Does the in situ technique provide better long-term patency of femoro-distal
bypass reconstruction?
PMID- 29943960
TI - Is late open conversion after TEVAR more risky than primary open repair of
descending thoracic aneurysms?
PMID- 29943961
TI - Techniques and outcomes of false lumen embolization in chronic type B aortic
dissection.
AB - Endovascular strategies have been increasingly used for the treatment of chronic
type B aortic dissection (cTBAD) offering better outcomes in terms of mortality
and morbidity compared to open surgical repair. Aortic remodeling after standard
TEVAR is less likely in cTBAD due to rigidity of the dissection membrane. Another
limitation of endovascular therapy is continued retrograde false lumen perfusion
with back-flow from distal entry tears. Treatment strategies in cTBAD should aim
at false lumen thrombosis. There are many approaches to achieve this goal of
false lumen thrombosis, but concepts as open surgery or fenestrated and branched
endovascular repair are limited by either high technical and logistic demands to
the surgeon or high rates of mortality and morbidity. False lumen embolization
techniques offer less invasive treatment strategies with promising early results.
The main strategies for false lumen embolization include the "cork in the bottle
neck" technique, the Candy-Plug technique or the Knickerbocker-technique. This
article describes technical aspects and early results of these new endovascular
techniques of false lumen embolization in chronic aortic dissection.
PMID- 29943962
TI - Graft design and selection of fenestrations vs branches for renal and mesenteric
incorporation in endovascular treatment of pararenal and thoracoabdominal aortic
aneurysms.
AB - To address target vessels in pararenal and thoracoabdominal aortic aneurysms with
fenestrated and branched grafts, two solutions are available: fenestrations
(holes in the graft) and directional side-branches. Fenestrations work well for
target vessels that have a close to 90-degree take-off from the aorta, and when
the main graft at the level of the target vessel is adjacent or close to the
aortic wall. Directional side-branches work well when target vessels have a
steeper take-off angle and when there is a larger gap to be bridged. A third
option of "inner branches" has been evaluated by our group to address target
vessels that are not very suitable for either a fenestration or a directional
side- branch. Most pararenal aneurysms are treated with fenestrated grafts,
whereas thoraco- abdominal aneurysms are treated mostly by grafts incorporating
both fenestrations and branches. In Nuremberg, 347 patients were treated with
fenestrated/branched grafts for thoraco- abdominal aneurysms. A stent-graft with
fenestrations only was used in 108 (31.1%) patients, a stent-graft with branches
only in 104 (30.0%) patients, and a stent-graft with a combination of
fenestrations and branches in 135 (38.9%) patients. For the RAs (n=625)
fenestrations were used in 408 (65.3%) and branches in 217 (34.7%). For the SMA
(n=341) fenestrations were used in 169 (49.6%) and branches in 172 (50.4%). For
the CA (n=297), fenestrations were used in 84 (28.3%), and branches in 213
(71.7%). Target vessel patency at 3 years was 98.2 +/-0.9% for vessels targeted
with fenestrations and 92.2+/-1.9% for vessels targeted with branches (p=0.009).
PMID- 29943963
TI - Techniques and outcomes of secondary open repair for chronic dissection after
acute repair of type A aortic dissection.
AB - Despite successful repair of acute type A aortic dissection (TAAD), the distal
false lumen may remain patent resulting in progressive degeneration of the
remaining distal aorta. This can lead to aneurysmal dilatation and risk of
rupture. Open distal reoperation to replace the residually dissected thoraco
abdominal aorta may be accomplished with acceptable morbidity and mortality in
experienced hands. This can be facilitated when the index operation for acute
TAAD is tailored to exclude all primary tears and set the arch and descending
aorta for a subsequent open, endovascular or hybrid procedure.
PMID- 29943964
TI - Quantitative Studies on the Structure of Molten Binary Potassium Molybdates by in
Situ Raman Spectroscopy and Quantum Chemistry ab Initio Calculations.
AB - The quantitative distribution of different species ( Q ijklm and H ijklmno) in
binary potassium molybdate melts has been investigated by in situ high
temperature Raman spectroscopy in conjunction with quantum chemistry (QC) ab
initio calculations. The symmetric stretching vibrational wavenumbers of
molybdenum nonbridging oxygen bonds in high wavenumber range and their
respectively corresponding Raman scattering cross sections were determined and
analyzed. Deconvolution of the stretching bands of molybdenum nonbridging oxygen
bonds of molten Raman spectra by using the Voigt function was carried out. The
six-coordinated molybdenum oxygen octahedra [MoO6]6- have been proposed to be
present in molten molybdates, apart from the well-known existence of the four
coordinated [MoO4]2- tetrahedra. The quantitative analysis of different species
in the molten K2MoO4-MoO3 system and their dependence on the content of MoO3, as
well as the relationship with the viscosities of the melts, were also discussed.
The quantitative results have been integrated with published data on physical and
chemical properties of the melts.
PMID- 29943965
TI - Toward Better Understanding of EBPR Systems via Linking Raman-Based Phenotypic
Profiling with Phylogenetic Diversity.
AB - This study reports a proof-of concept study to demonstrate the novel approach of
phenotyping microbial communities in enhanced biological phosphorus removal
(EBPR) systems using single cell Raman microspectroscopy and link it with
phylogentic structures. We use hierarchical clustering analysis (HCA) of single
cell Raman spectral fingerprints and intracellular polymer signatures to separate
and classify the functionally relevant populations in EBPR systems, namely
polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms
(GAOs), as well as other microbial populations. We then investigated the link
between Raman-based community phenotyping and 16S rRNA gene-based phylogenetic
characterization of four lab-scale EBPR systems with varying solid retention time
(SRT) to gain insights into possible genotype-function relationships. Combined
and simultaneous phylogenetic and phenotypic evaluation of EBPR ecosystems
revealed SRT-dependent phylogenetic and phenotypic characteristics of the PAOs
and GAOs, and their association with EBPR performance. The phenotypic diversity
and plasticity of PAO populations, which otherwise could not be obtained with
phylogenetic analysis alone, showed complex but potentially crucial association
with EBPR process stability.
PMID- 29943966
TI - In Situ Spectroelectrochemical Studies into the Formation and Stability of Robust
Diazonium-Derived Interfaces on Gold Electrodes for the Immobilization of an
Oxygen-Tolerant Hydrogenase.
AB - Surface-enhanced infrared absorption spectroscopy is used in situ to determine
the electrochemical stability of organic interfaces deposited onto the surface of
nanostructured, thin-film gold electrodes via the electrochemical reduction of
diazonium salts. These interfaces are shown to exhibit a wide electrochemical
stability window in both acetonitrile and phosphate buffer, far surpassing the
stability window of thiol-derived self-assembled monolayers. Using the same in
situ technique, the application of radical scavengers during the electrochemical
reduction of diazonium salts is shown to moderate interface formation.
Consequently, the heterogeneous charge-transfer resistance can be reduced
sufficiently to enhance the direct electron transfer between an immobilized redox
active enzyme and the electrode. This was demonstrated for the oxygen-tolerant
[NiFe] hydrogenase from the "Knallgas" bacterium Ralstonia eutropha by relating
its electrochemical activity for hydrogen oxidation to the interface properties.
PMID- 29943967
TI - Mesenchymal Stem Cell/Red Blood Cell-Inspired Nanoparticle Therapy in Mice with
Carbon Tetrachloride-Induced Acute Liver Failure.
AB - Acute liver failure is a critical condition characterized by global hepatocyte
death and often time needs a liver transplantation. Such treatment is largely
limited by donor organ shortage. Stem cell therapy offers a promising option to
patients with acute liver failure. Yet, therapeutic efficacy and feasibility are
hindered by delivery route and storage instability of live cell products. We
fabricated a nanoparticle that carries the beneficial regenerative factors from
mesenchymal stem cells and further coated it with the membranes of red blood
cells to increase blood stability. Unlike uncoated nanoparticles, these particles
promote liver cell proliferation in vitro and have lower internalization by
macrophage cells. After intravenous delivery, these artificial stem cell analogs
are able to remain in the liver and mitigate carbon tetrachloride-induced liver
failure in a mouse model, as gauged by histology and liver function test. Our
technology provides an innovative and off-the-shelf strategy to treat liver
failure.
PMID- 29943968
TI - Toward an Intensive Longitudinal Understanding of Activated Sludge Bacterial
Assembly and Dynamics.
AB - Temporal microbial community studies have broadened our knowledge of the dynamics
and correlations among microbes in both natural and artificial engineering
systems. Using activated sludge as a model system, we utilized the intensive
longitudinal sampling method to identify overlooked diversity and the hidden
dynamics of microbes, detect cross-associations among microbes after detrending,
and reveal the central microbial dynamics during sludge bulking and foaming. We
discovered that the accumulative alpha diversity in activated sludge sampled
daily over 392 days could be as high as 14 000 OTUs, and that the bacterial
community dynamics followed a gradual succession, drifting away from the initial
observed day and displaying a significant time-dependent trend. Cross
associations among bacteria were modulated after removing potential spurious
correlations based on autocorrelation in microbial time series. Moreover,
clusters of bacteria displaying rapid turnover were discovered during the
beginning, ongoing, and fading of sludge bulking and foaming, and their
physicochemical parameters are resolved. These identified groups of bacteria and
their related environmental factors could potentially supply clues to form
hypotheses for treating operational problems, such as sludge bulking and foaming.
PMID- 29943969
TI - High-Throughput and Sensitive Fluorimetric Strategy for MicroRNAs in Blood Using
Wettable Microwells Array and Silver Nanoclusters with Red Fluorescence Enhanced
by Metal Organic Frameworks.
AB - A high-throughput and sensitive fluorimetric analysis method has been developed
with wettable microwells array for probing short-chain microRNAs (miRNAs) in
blood using silver nanoclusters (AgNCs) with red fluorescence amplified and
stabilized by metal organic frameworks (MOFs). Glass slides were first spotted
with polyacrylic acid to form hydrophilic microdots and then patterned with
hydrophobic hexadecyltrimethoxysilane, followed by etching the microdots to yield
the microwells array. Furthermore, the DNA capture probes with silver-binding G
sequences were covalently bound onto the functionalized microwells to hybridize
with targeting miRNAs. Exonuclease I catalytic digestion was then conducted to
remove any single-strand DNA probes unhybridized. Eventually, AgNCs were applied
to specifically recognize the G sequences of DNA probes survived to be further
coated with MOFs of zeolitic imidazolate framework (ZIF-8). Unexpectedly, the red
fluorescence of AgNCs probes could be dramatically enhanced due to the "electron
donor effect" of nitrogen-containing ligands of ZIF-8 coatings, together with
improved sensing stability. High detection sensitivity and reproducibility could
thereby be expected for detecting miRNAs in the blood with the concentrations
linearly ranging from 0.175 to 500 pM. Markedly different from the common
sandwiched DNA detection methods, the developed fluorimetric strategy using AgNCs
coated with MOFs and DNA probes designed with silver-recognizing sequences would
be tailored for quantifying various kinds of short-chain miRNAs with low levels
in the complicated blood media.
PMID- 29943970
TI - Successive and Specific Detection of Hg2+ and I- by a DNA@MOF Biosensor:
Experimental and Simulation Studies.
AB - A 2D metal-organic framework (MOF) of {[Cu(Dcbb)(Bpe)].Cl} n (1, H2DcbbBr = 1
(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide, Bpe = trans-1,2-bis(4
pyridyl)ethylene)) has been prepared. MOF 1 associates with the thymine-rich (T
rich), single-stranded probe DNA (ss-DNA, denoted as P-DNA) labeled with
fluorophore FAM (FAM = carboxyfluorescein) and quenches the FAM emission to give
a nonemissive P-DNA@1 hybrid (off state). The P-DNA in the hybrid subsequently
captures the Hg2+ to give a rigid double-stranded DNA featuring T-Hg2+-T motif
(ds-DNA@Hg2+) and detach from MOF 1, triggering the recovery of the FAM
fluorescence (on state). Upon subsequent addition of I-, Hg2+ was further
sequestrated from the ds-DNA@Hg2+ duplex, driven by the stronger Hg-I
coordination. The released P-DNA is resorbed by MOF 1 to regain the initial P
DNA@1 hybrid (off state). The P-DNA@1 sensor thus detects Hg2+ and I-
sequentially via a fluorescence "off-on-off" mechanism. The sensor is highly
selective and sensitive, yielding detection limits of 3.2 and 3.3 nM,
respectively. The detection process was conformed by circular dichroism (CD) and
the detection mechanism was verified by fluorescence anisotropy, binding
constant, and simulation of the binding free energy at each stage.
PMID- 29943971
TI - Alterations to the Intestinal Microbiome and Metabolome of Pimephales promelas
and Mus musculus Following Exposure to Dietary Methylmercury.
AB - Mercury is a global contaminant, which may be microbially transformed into
methylmercury (MeHg), which bioaccumulates. This results in potentially toxic
body burdens in high trophic level organisms in aquatic ecosystems and maternal
transfer to offspring. We previously demonstrated effects on developing fish
including hyperactivity, altered time-to-hatch, reduced survival, and
dysregulation of the dopaminergic system. A link between gut microbiota and
central nervous system function in teleosts has been established with
implications for behavior. We sequenced gut microbiomes of fathead minnows
exposed to dietary MeHg to determine microbiome effects. Dietary exposures were
repeated with adult CD-1 mice. Metabolomics was used to screen for metabolome
changes in mouse brain and larval fish, and results indicate effects on lipid
metabolism and neurotransmission, supported by microbiome data. Findings suggest
environmentally relevant exposure scenarios may cause xenobiotic-mediated
dysbiosis of the gut microbiome, contributing to neurotoxicity. Furthermore,
small-bodied teleosts may be a useful model species for studying certain types of
neurodegenerative diseases, in lieu of higher vertebrates.
PMID- 29943972
TI - Controlled Movement of a Smart Miniature Submarine at Various Interfaces.
AB - Smart miniaturized aquatic devices have many important applications, but their
locomotion at different interfaces remains a challenge. Here, we report a smart
miniaturized submarine moving at various air/liquid or oil/water interfaces. The
microsubmarine is fabricated by a CO2-responsive superhydrophobic copper mesh and
is driven by the Marangoni effect. The microsubmarine can not only transfer among
different interfaces reversibly but also move horizontally at the interfaces
freely. The unique locomotion of the device is attributed to a CO2-triggered
switch between superhydrophobicity and underwater superoleophobicity. Moreover,
the microsubmarine exhibits good stability and excellent oil repellence at the
oil/water interface. Our study provides a strategy for fabricating smart aquatic
devices that have potential applications in environment monitoring, water
purification, channel-free microfluidics, and so on.
PMID- 29943973
TI - Regulation Effects of Biomimetic Hybrid Scaffolds on Vascular Endothelium
Remodeling.
AB - The formation of complete and well-functioning endothelium is critical for the
success of tissue-engineered vascular grafts yet remaining a fundamental
challenge. Endothelium remodeling onto the lumen of tissue-engineered vascular
grafts is affected by their topographical, mechanical, and biochemical
characteristics. For meeting multiple requirements, composite strategies have
recently emerged for fabricating hybrid scaffolds, where the integrated
properties are tuned by varying their compositions. However, the underlying
principle how the integrated properties of hybrid scaffolds regulate vascular
endothelium remodeling remains unclear. To uncover the regulation effects of
hybrid scaffolds on vascular endothelium remodeling, we prepared different
biomimetic hybrid scaffolds using gelatin methacrylamide (GelMA) and poly-epsilon
caprolactone (PCL) and then investigated vascular endothelial cell responses on
them. GelMA and PCL, respectively, conferred the resulting scaffolds with
biomimetic bioactivity and mechanical properties, which were tuned by varying
GelMA/PCL mass ratios (3:1, 1:1, or 1:3). On different GelMA/PCL hybrid
scaffolds, distinct vascular endothelial cell responses were observed. Firm cell
scaffold/cell-cell interactions were rapidly established on the hybrid scaffolds
with the highest mass ratio of bioactive GelMA. However, they were mechanically
insufficient as vascular grafts. On the contrary, the scaffolds with the highest
mass ratio of PCL showed significantly reinforced mechanical properties but poor
biological performance. Between the two extremes, the scaffolds with the same
GelMA/PCL mass ratio balanced the pros and cons of two materials. Therefore, they
could meet the mechanical requirements of vascular grafts and support the early
stage vascular endothelial cell remodeling by appropriate biological signaling
and mechanotransduction. This investigation experimentally proves that scaffold
bioactivity is the dominant factor affecting vascular endothelial cell adhesion
and remodeling, whereas mechanical properties are crucial factors for the
integrity of endothelium. This work offers a universal design strategy for
desirable vascular grafts for improved endothelium remodeling.
PMID- 29943974
TI - Boosting the Deep Discharging/Charging Lithium Storage Performances of Li3VO4
through Double-Carbon Decoration.
AB - With high theoretical capacity, good ionic conductivity, and suitable working
plateaus, Li3VO4 has emerged as an eye-catching intercalation anode material for
lithium storage. However, Li3VO4 suffers from poor electrical conductivity and
20% volume variation under deep discharging/charging conditions. Herein, we
present a "double-carbon decoration" strategy to tackle both issues. Deflated
balloon-like Li3VO4/C/reduced graphene oxide (LVO/C/rGO) microspheres with
continuous electron transport pathways and sufficient free space for volume
change accommodation are fabricated through a facile spray-drying method. Under
deep discharging/charging conditions (0.02-3.0 V), LVO/C/rGO achieves a high
intercalation capacity of 591 mA h g-1. With high capacity and outstanding
stability, LVO/C/rGO outperforms other intercalation anode materials (such as
graphite, Li4Ti5O12, and TiO2). In situ X-ray diffraction measurement reveals
that the lithium storage is realized through both solid-solution reaction and two
phase reaction mechanisms. A LVO/C/rGO//LiNi0.8Co0.15Al0.05O2 lithium-ion full
cell is also assembled. In such full cell, LVO/C/rGO also demonstrates high
specific capacity and excellent cycling stability. The above results manifest
that the LVO/C/rGO anode has the potential to be applied in the next-generation
high-performance lithium-ion batteries.
PMID- 29943975
TI - Multishell Precursors Facilitated Synthesis of Concentration-Gradient Nickel-Rich
Cathodes for Long-Life and High-Rate Lithium-Ion Batteries.
AB - The rational design of concentration-gradient (CG) structure is demonstrated as
an available approach to improve the electrochemical performances of high-energy
nickel-rich cathodes for lithium-ion batteries (LIBs). However, the complicated
preparing processes, especially the CG-precursors, generally result in the less
than-ideal repeatability and consistency that is regarded as an extreme challenge
for the widespread commercialization. Thus, the innovative strategy with facile
steps and the feasibility of large-scale preparation for commercialized
applications should be urgently developed. Herein, through the temperature
tunable cation diffusion, the feasibility of controllable preparation of nickel
rich CG-LiNi0.7Co0.15Mn0.15O2 (NCM) from multishell precursors is first
demonstrated. As expected, the Li/CG-NCM half cells show much enhanced cycle
life, rate property, and safety because of the mitigated side-reactions and fast
Li+ kinetics. Besides, the Li4Ti5O12/CG-NCM full cells also exhibit long-term
lifespan, 95% capacity retention even after 2000 cycles, and high-rate behaviors.
Importantly, by contrast with the conventional techniques that prepare CG
cathodes from CG precursors, the proposed new synthesis strategy from multishell
precursors is suitable for large-scale preparation. Overall, this multishell
precursor-facilitated synthesis probably promotes the practical applications of
CG cathodes for state-of-the-art LIBs and also can be easily expanded to
controllably preparing spinel- and olive-type CG cathodes.
PMID- 29943976
TI - Large-Scale Assessment of Extractables and Leachables in Single-Use Bags for
Biomanufacturing.
AB - Single-use technologies (SUTs) are widely used during biopharmaceutical
manufacture as disposable bioreactors or media and buffer storage bags. Despite
their advantages, the risk of release of extractable and leachable (E&Ls)
substances is considered an important drawback in adopting disposables in the
biomanufacturing process. E&Ls may detrimentally affect cell viability or
productivity or may persist during purification and present a risk to the patient
if remaining in the final drug product. In this study, 34 plastic films from
single-use bags (SUBs) for cell cultivation were extracted with selected solvents
that represent reasonable worst-case conditions for most typical biomanufacturing
applications. SUBs were incubated at small-scale under accelerated-aging
conditions that represented standard operational conditions of use. Leachables
analysis was performed following dispersive liquid-liquid microextraction (DLLME)
for analyte preconcentration and removal of matrix interference. Resulting
extracts were characterized by GC-headspace for volatiles, high resolution GC
Orbitrap-MS/MS for semivolatiles, high resolution LC-Orbitrap-MS/MS for
nonvolatiles, and ICP-MS for trace elemental analysis. Multivariate statistical
analysis of the analytical data revealed significant correlations between the
type and concentration of compounds and bags features including brand,
manufacturing date and polymer type. The analytical data demonstrates that, over
recent years, the nature of E&Ls has been altered due to the implementation of
manufacturing changes and new types of polymers and may change further with the
future advent of regulations that will limit or ban the use of certain raw
materials and additives. The broad E&L database generated herein facilitates
toxicological assessments from a biomanufacturing standpoint and provides
practical guidelines for confident determination of E&Ls to enable screening and
elimination of nonsatisfactory films for single use bioprocessing.
PMID- 29943977
TI - High-Resolution Ion Mobility Spectrometry for Rapid Cannabis Potency Testing.
AB - We report initial results from an ion mobility spectrometry (IMS)-based analysis
of natural cannabis samples and explore the possibility of using this technique
to distinguish medical marijuana from illegal forms of the drug, as defined by
Swiss legislation. We analyzed cannabis extracts by electrospray ionization IMS
MS and found that high-resolution drift-tube IMS ( R > 150) can effectively
isolate and quantify the controlled substance, Delta9-tetrahydrocannabinol (THC),
even in the presence of other noncontrolled cannabinoid isomers including
cannabidiol (CBD). We used this information to determine whether the THC content
of a given sample surpassed the legal limit, which is 1% by weight in
Switzerland. Our IMS-MS methodology produced equivalent quantification results to
standard HPLC-based methods and offers the additional advantage of significantly
shorter time requirements for the analysis. In addition, IMS-based analysis
offers flexibility over HPLC in that it can be performed on portable devices. As
such, these findings may have implications for cannabis testing in police
laboratories.
PMID- 29943978
TI - Covalently Cross-Linked Elastomers with Self-Healing and Malleable Abilities
Enabled by Boronic Ester Bonds.
AB - Covalently cross-linked rubbers are renowned for their high elasticity that play
an indispensable role in various applications including tires, seals, and medical
implants. Development of self-healing and malleable rubbers is highly desirable
as it allows for damage repair and reprocessability to extend the lifetime and
alleviate environmental pollution. Herein, we propose a facile approach to
prepare permanently cross-linked yet self-healing and recyclable diene-rubber by
programming dynamic boronic ester linkages into the network. The network is
synthesized through one-pot thermally initiated thiol-ene "click" reaction
between a novel dithiol-containing boronic ester cross-linker and commonly used
styrene-butadiene rubber without modifying the macromolecular structure. The
resulted samples are covalently cross-linked and possess relatively high
mechanical strength which can be readily tailored by varying boronic ester
content. Owing to the transesterification of boronic ester bonds, the samples can
alter network topologies, endowing the materials with self-healing ability and
malleability.
PMID- 29943979
TI - Synthesis, Structure, and Cytotoxicity of Oxaliplatin-Based Platinum(IV)
Anticancer Prodrugs Bearing One Axial Fluoride.
AB - Fluorine plays more and more important roles in drug design and development. In
recent years, fluorine-containing organic drugs have already been applied in a
broad range of therapeutic areas. Herein, we report our attempt to introduce an
axial fluorine ligand to Pt(IV) complexes by oxidizing oxaliplatin with
electrophilic fluorinating reagents in different protic solvents. The crystal
structure of one representative complex is presented. The fluorinated Pt(IV)
complexes are further expanded by functionalization with different anhydrides,
and their analogues bearing one different axial ligand (OAc or OH group) are also
synthesized. Further investigations show that the axial fluorine atom has
dramatic effects on the chemical properties of these prodrugs. These new
fluorinated Pt(IV) complexes are proved to be stable in physiological conditions.
For most of the fluorinated Pt(IV) complexes, a higher reduction potential
indicates its greater tendency to be reduced by ascorbate. Introducing an axial
fluorine ligand in Pt(IV) complexes does not lead to the increase of their
lipophilicity. Moreover, these new fluorinated Pt(IV) complexes show better
cytotoxicity than nonfluorinated analogues which may derive from their higher
cellular accumulation in cancer cells. Therefore, the good stability and high
cytotoxicity of these fluorinated Pt(IV) prodrugs indicate their great potential
as a building block for further functionalization.
PMID- 29943980
TI - Chiral BINAPO-Controlled Diastereoselective Self-Assembly and Circularly
Polarized Luminescence in Triple-Stranded Europium(III) Podates.
AB - Chiral lanthanide helical architectures have received intense attentions in
recent years because of their potential applications as chiral probes and sensors
and as circularly polarized luminescence (CPL) materials. However,
stereoselectivity control in the self-assembly of lanthanide helicate is
challenging due to the poor stereochemical preference and variable coordination
numbers of Ln(III) ions. Herein, we reported the employing chiral ancillary
ligand R/S-BINAPO to induce achiral tripodal ligand to form a pair of homochiral
lanthanide triple-helical podates [Eu(TTEA)((R/S)-BINAPO); R/S-1] {(R/S)-BINAPO =
( R/ S)-2,2'-bis(diphenylphosphoryl)-1,1'-binaphthyl; TTEA = tris[(4-(4,4,4
trifluoro-1,3-dioxobutyl)-benzamido)ethyl]amine}. X-ray crystallographic analysis
for rac-1 reveals that the chirality of BINAPO is transferred during the self
assembly process to give either P or M helical architectures in podates. The 1H
and 31P NMR and circular dichroism measurements confirm the diastereopurity of
the assemblies in solution. A detailed optical and chiroptical characterization
reveals that the luminescent enantiopure podates not only exhibit intense CPL
with | glum| values reaching 0.072 but also show high luminescence quantum yields
of 32.8%. Our results provide a feasible strategy for designing homochiral
helical lanthanide supramolecular architecture and synthesizing excellent CPL
materials.
PMID- 29943981
TI - Specific Imaging of Tyrosinase in Vivo with 3-Hydroxybenzyl Caged D-Luciferins.
AB - Tyrosinase (TYR), a key enzyme in biosynthesis of melanin, usually functions as a
biomarker of severe skin diseases such as vitiligo and melanoma cancer. Accurate
detection of TYR activity in vivo is urgent but still challenging. Inspired by
the advantages of bioluminescence in vivo strategy in imaging and the specific
hydroxylation of 3-hydroxybenzyloxy group by TYR, a bioluminogenic probe, TYR
LH2, was designed and synthesized through caging D-luciferin with 3
hydroxybenzyl. The probe exhibits high selectivity and sensitivity toward TYR
with a detection limit of 0.11 U/mL in a small detection volume of 100 MUL.
Bioluminescence imaging results show that TYR-LH2 is fully competent for
monitoring the dynamic changes of TYR in living cells and model animals and
possesses the capability of discriminating melanocytes from other cell lines,
thus offering a promising approach for investigation and diagnosis of melanoma
cancer and other TYR-related diseases in vivo.
PMID- 29943982
TI - In Situ Growth of NiFe Alloy Nanoparticles Embedded into N-Doped Bamboo-like
Carbon Nanotubes as a Bifunctional Electrocatalyst for Zn-Air Batteries.
AB - Developing low-cost catalysts for electrochemical oxygen reduction reaction (ORR)
and oxygen evolution reaction (OER) with superior performance in an alkaline
solution is of significance for large-scale applications in aqueous zinc-air
batteries (ZABs). Herein, we describe the in situ design of embedded NiFe
nanoparticles into the N-doped bamboo-like carbon nanotube (NBCNT) with high
catalytic performance and stability. The obtained NiFe@NBCNT hybrid exhibits a
high electrochemical activity and stability with an unexpectedly low
overpotential of ~195 mV for OER at 10 mA cm-2 and an onset potential at 1.03 V
for ORR, superior to the state-of-the-art Pt/C and RuO2 catalysts. Additionally,
compared to the mixture of Pt/C and RuO2 cathodes, the ZAB based on the
NiFe@NBCNT cathode displays a lower overpotential (0.80 V), higher stable round
trip efficiency (58.3%), and improved power density for 200 cycles at 10 mA cm-2.
Apparently, the obtained results indicate that the NiFe@NBCNT hybrid is proven to
be one of the best nonnoble metal catalysts for achieving commercial
implementation of rechargeable ZABs.
PMID- 29943983
TI - How Much Bean Hemagglutinin Is Safe for Human Consumption?
PMID- 29943984
TI - Total Syntheses of Thailanstatins A-C, Spliceostatin D, and Analogues Thereof.
Stereodivergent Synthesis of Tetrasubstituted Dihydro- and Tetrahydropyrans and
Design, Synthesis, Biological Evaluation, and Discovery of Potent Antitumor
Agents.
AB - Efficient and selective total syntheses of spliceosome modulating natural
products thailanstatins A-C and spliceostatin D are reported. A number of
stereoselective methods for the construction of various tetrasubstituted dihydro-
and tetrahydropyrans were developed as a prerequisite for the syntheses of these
naturally occurring molecules and variations thereof. The pyran-forming reactions
utilize a Heck/Saegusa-Ito cascade sequence to generate hydroxy
alpha,beta,gamma,delta-unsaturated aldehyde precursors followed by a catalyst
controlled oxa-Michael cyclization to furnish tetrasubstituted dihydropyrans with
high stereocontrol. Subsequent optimized homogeneous or heterogeneous
hydrogenations of these dihydropyran systems afford their tetrahydropyran
counterparts, also in a highly stereoselective manner. The synthesized
thailanstatins and related analogues were biologically evaluated for their
cytotoxic properties, leading to the identification of a number of compounds with
exceptionally potent antitumor activities suitable for further development as
potential antibody-drug conjugate payloads, single drugs, or drug combinations
for cancer therapies. Important structure-activity relationships within the
thailanstatin family and structurally related compounds are discussed and are
expected to be path-pointing for future studies.
PMID- 29943985
TI - Versatile Control of Directed Supramolecular Assembly via Subtle Changes of the
Rhodium(I) Pincer Building Blocks.
AB - Various rhodium(I) pincer complexes with different structural features have been
prepared and found to display interesting self-assembly properties due to the
extensive Rh(I)...Rh(I) interactions. The incorporation of electron-withdrawing
CF3 substituent has been found to improve the stability of the complexes and also
facilitate the directed assembly of complex molecules, providing an opportunity
for the systematic investigation of the various noncovalent interactions in their
versatile self-assembly behaviors and insights into the structure-property
relationship in governing the intermolecular interactions. An isodesmic growth
mechanism is identified for the solvent-induced aggregation process. The complex
molecules exhibit intense low-energy absorption bands corresponding to the
absorptions of the dimers, trimers, and higher order oligomers upon aggregation,
with energies related to the electronic properties of the tridentate N-donor
ligand. Chiral auxiliaries have also been introduced into the rhodium(I)
complexes to build up helical supramolecular assemblies and soft materials.
PMID- 29943987
TI - Applying Molecular Networking for the Detection of Natural Sources and Analogues
of the Selective Gq Protein Inhibitor FR900359.
AB - The cyclic depsipeptide FR900359 (FR), isolated from the traditional Chinese
medicine plant Ardisia crenata, is a potent Gq protein inhibitor and thus a
valuable tool to study Gq-mediated signaling of G protein-coupled receptors. Two
new FR analogues (3 and 4) were isolated from A. crenata together with the known
analogues 1 and 2. The structures of compounds 3 and 4 were established by NMR
spectroscopic data and MS-based molecular networking followed by in-depth LCMS2
analysis. The latter approach led to the annotation of further FR analogues 5-9.
Comparative bioactivity tests of compounds 1-4 along with the parent molecule FR
showed high-affinity binding to Gq proteins in the low nanomolar range (IC50 =
2.3-16.8 nM) for all analogues as well as equipotent inhibition of Gq signaling,
which gives important SAR insights into this valuable natural product.
Additionally, FR was detected from leaves of five other Ardisia species, among
them the non-nodulated leaves of Ardisia lucida, implying a much broader
distribution of FR than originally anticipated.
PMID- 29943986
TI - 1-Octen-3-ol Is Formed from Its Glycoside during Processing of Soybean [ Glycine
max (L.) Merr.] Seeds.
AB - Soaking and maceration of dry soybean seeds induce the formation of aliphatic
volatile compounds that impact the flavor properties of food products prepared
from soybean. Most aliphatic volatile compounds are formed through oxygenation of
unsaturated fatty acids by lipoxygenases; however, lipoxygenases are not
responsible for the formation of 1-octen-3-ol. 1-Octen-3-ol in soybean products
is in general an off-flavor compound; thus, a procedure to manage its formation
is required. In this study, we show that the formation of 1-octen-3-ol after
hydration of soybean seed powder is independent of oxygen, suggesting that 1
octen-3-ol is not formed de novo from unsaturated fatty acids but instead from
its derivative. When crude methanol extract of soybean seeds was reacted with
beta-glycosidases, 1-octen-3-ol was rather liberated from its glycoside. We
purified the parent glycoside from soybean seeds and confirmed it as ( R)-1-octen
3-yl beta-primeveroside [( R)-1-octen-3-yl 6- O-beta-d-xylopyranosyl-beta-d
glucopyranoside]. Green immature soybean fruits (pericarp and seeds) contain a
high amount of 1-octen-3-yl beta-primeveroside. Its amount decreases after
hydration of dry soybean powder. The results indicate that management of 1-octen
3-ol levels in soybean products requires a different strategy than that applied
to off-flavor compounds formed de novo.
PMID- 29943988
TI - Granular, Slow-Release Fertilizer from Urea-formaldehyde, Ammonium Polyphosphate,
and Amorphous Silica Gel: A New Strategy Using Cold Extrusion.
AB - A new granular, slow-release fertilizer prepared by a cold-extrusion strategy
(GSRFEx) based on urea-formaldehyde (UF), ammonium polyphosphate (APP), and
amorphous silica gel (ASG) was presented. Characterizations showed that there
were strong hydrogen-bond interactions and good compatibility among UF, APP, and
ASG in GSRFEx. The mechanical properties as well as the slow-release properties
of GSRFEx were greatly enhanced after the addition of APP and ASG to UF. Rape pot
experiments indicated that GSRFEx could improve N-use efficiency dramatically and
thereby facilitate the growth of rape. Importantly, as an economical, effective,
and environment-friendly technology, cold extrusion has great potential to be
applied in horticulture and agriculture. We hope that our work can offer an
alternative method for the design of slow-release fertilizers with desirable
properties.
PMID- 29943989
TI - Second-Generation Synthesis of (+)-Fastigiatine Inspired by Conformational
Studies.
AB - (+)-Fastigiatine is a complex alkaloid isolated from the alpine club moss
Lycopodium fastigatum, most commonly found in New Zealand. It has been the
subject of two successful synthetic campaigns. A second-generation route toward
fastigiatine was developed to resolve two problematic steps from our initial
synthesis. Selective reduction and protection of the C13 ketone improved the
yield and reliability of the dibromocarbene ring expansion step. In the prior
synthesis, cuprate addition to the C10 enone generated a 1:1 mixture of isomers
in an advanced intermediate. Protection of the C13 alcohol with a large silyl
group changed the conformational preference of the enone and led to a more
selective conjugate addition to produce the desired beta-epimer at C10.
MacMillan's decarboxylative photoredox addition method proved to be more
practical than the prior aminomethyl cuprate addition chemistry. The second
generation synthesis is longer than the original but improves the selectivity and
reproducibility of the overall route.
PMID- 29943990
TI - Correction to Synergistic Chemopreventive and Therapeutic Effects of Co-drug UA
Met: Implication in Tumor Metastasis.
PMID- 29943991
TI - Synthesis of Polyheterocyclic Tropones by [2 + 2 + 2 + 1] Carbonylative
Cycloaddition of Triynes.
AB - A direct synthesis of tropones (2,4,6-cycloheptatrienes) from simple preorganized
triynes has been elaborated. This simple rhodium-catalyzed domino strategy allows
one-pot access to fully substituted tropones in a 6-6-7-5 tetracyclic core in
average to high yields.
PMID- 29943992
TI - Visible-Light-Mediated Nickel(II)-Catalyzed C-N Cross-Coupling in Water: Green
and Regioselective Access for the Synthesis of Pyrazole-Containing Compounds.
AB - A regioselective green approach for the nickel(II)-catalyzed C-N cross-coupling
between arylamines and pyrazoles through a photoredox process is reported.
Moderate to good yield was observed for this reaction, performed in water under
air at room temperature. This strategy provides a powerful tool for the green
synthesis of pyrazole-containing bioactive molecules. In addition, a single
electron-transfer mechanism is proposed in this report.
PMID- 29943993
TI - Correlative Single-Molecule FRET and DNA-PAINT Imaging.
AB - DNA-PAINT is an optical super-resolution microscopy method that can visualize
nanoscale protein arrangements and provide spectrally unlimited multiplexing
capabilities. However, current multiplexing implementations based on, for
example, DNA exchange (such as Exchange-PAINT) achieves multitarget detection by
sequential imaging, limiting throughput. Here, we combine DNA-PAINT with single
molecule FRET and use the FRET efficiency as parameter for multiplexed imaging
with high specificity. We demonstrate correlated single-molecule FRET and super
resolution on DNA origami structures, which are equipped with binding sequences
that are targeted by pairs of dye-labeled oligonucleotides generating the FRET
signal. We futher extract FRET values from single binding sites that are spaced
just ~55 nm apart, demonstrating super-resolution FRET imaging. This combination
of FRET and DNA-PAINT allows for multiplexed super-resolution imaging with low
background and opens the door for accurate distance readout in the 1-10 nm range.
PMID- 29943994
TI - Multicomponent Reaction Based Synthesis of 1-Tetrazolylimidazo[1,5- a]pyridines.
AB - A series of unprecedented tetrazole-linked imidazo[1,5- a]pyridines are
synthesized from simple and readily available building blocks. The reaction
sequence involves an azido-Ugi-deprotection reaction followed by an acetic
anhydride-mediated N-acylation-cyclization process to afford the target
heterocycle. Furthermore, the scope of the methodology was extended to diverse R3
substitutions by employing commercial anhydrides, acid chlorides, and acids as an
acyl component. The scope for the postmodification reactions are explored and the
usefulness of the synthesis is exemplified by an improved three-step synthesis of
a guanylate cyclase stimulator.
PMID- 29943995
TI - Asymmetric Construction of 3-Azabicyclo[3.1.0]hexane Skeleton with Five
Contiguous Stereogenic Centers by Cu-Catalyzed 1,3-Dipolar Cycloaddition of
Trisubstituted Cyclopropenes.
AB - A highly diastereo- and enantioselective desymmetrization of prochiral
cyclopropenes via a Cu(CH3CN)4BF4/Ph-Phosferrox complex catalyzed 1,3-dipolar
cycloaddition of azomethine ylides was described. A variety of complex 3
azabicyclo[3.1.0]hexane derivatives bearing five contiguous stereogenic centers
and two all-carbon quaternary stereogenic centers were directly synthesized as a
single isomer in excellent yields (up to 99%) and enantioselectivities (97 -> 99%
ee). Notably, various functional groups (CO2R, CN, CONMe2, and Ph) of
cyclopropenes were found to be well-tolerated in this transformation. The
cycloadduct was conveniently converted to a biologically important GABA
derivative via LiAlH4 reduction and subsequent hydrolysis.
PMID- 29943996
TI - Adsorption of Ultrathin Ethylene Carbonate Films on Pristine and Lithiated
Graphite and Their Interaction with Li.
AB - Aiming at a better understanding of the solid-electrolyte interphase formation in
Li-ion batteries, we have investigated the interaction of ultrathin films of
ethylene carbonate (EC), which is a key solvent of battery electrolytes, with
pristine and lithiated highly oriented pyrolytic graphite (HOPG) and with
postdeposited Li. Employing X-ray and ultraviolet photoelectron spectroscopy as
well as Fourier transform infrared spectroscopy under ultrahigh-vacuum
conditions, in combination with density functional theory (DFT)-based
calculations, we find that EC adsorbs molecularly intact on pristine HOPG in the
entire temperature range between 80 K and desorption at 200 K. Features in the
ultraviolet photoelectron spectra could be related to the molecular orbitals of
EC obtained from DFT calculations, and a similar adsorption/desorption behavior
is obtained also on lithiated HOPG. In contrast, stepwise postdeposition of ~0.5
and one monolayer of Li0 on a preadsorbed EC adlayer leads not only to
stabilization of Li+/Lidelta+ at the surface, possibly as adsorbed Li+(EC) n
species, but also to EC decomposition, forming products such as Li2CO3, ROCO2Li
(CH2OCO2Li)2, and Li2O. Consequences on the electronic surface properties and on
the stabilization of the resulting adlayer are discussed. Upon annealing up to
room temperature, some residual Li-containing decomposition products remain on
the surface, which is considered as the initial stage of the solid|electrolyte
interphase formation at the electrode|electrolyte interface.
PMID- 29943997
TI - Working as a medical doctor in the Calais migrant camp.
PMID- 29943998
TI - Assessing Mozambicans' willingness and determinants to use pre-exposure
prophylactic HIV medication.
AB - In anticipation of the introduction of the pre-exposure prophylaxis drugs as an
additional HIV prevention tool, we mapped the different positions of Mozambicans'
willingness to use it. Overall, 507 adults indicated willingness to use under
different conditions varying as a function of perceived susceptibility to and
severity of infection, side effects, administration protocol, and cost. Three
qualitatively different positions were found: Unwillingness irrespective of
conditions (4%), depend on circumstances (76%), and unconditional willingness
(8%). A large majority of participants were willing to use pre-exposure
prophylaxis drugs, provided that the administration is not too constraining, and
the adverse side effects can be minimized.
PMID- 29943999
TI - The tripartite structure of pain-related affect: a confirmatory factor analysis.
AB - Numerous emotion-based constructs seem related to pain and pain-related
disability. These include general affect constructs such as anxiety and
depression, as well as specific anxiety-related constructs such as anxiety
sensitivity and fear of pain. Few studies examine the relationships between these
constructs. Those that have suggest they can be reduced to three or four
underlying components. We used a confirmatory approach to test the models of pain
related anxiety found in previous exploratory studies. Adult participants (N =
294) completed commonly used measures of affect-related constructs relevant to
pain. Confirmatory Factor Analyses tested three models to determine the best fit.
The tripartite model, with small modifications, was found to provide the best
fit. The model consisted of: 1) General distress, 2) Fear of pain from
injury/insult, and 3) Cognitive intrusion of pain.
PMID- 29944000
TI - A new integrative approach to increase quality of life by reducing pain and fear
of movement in patients undergoing total hip arthroplasty: the IARA model.
AB - Total hip arthroplasty (THA) improve the patients' quality of life, and one of
the most important problems after surgery is to optimize postoperative pain
management. It has been shown that pain is intimately linked to the fear of
movement, the so-called kinesiophobia, which can affect the entire perioperative
period and quality of life in people undergoing THA. In this study, we aimed to
present a new integrative approach called IARA model specifically focused on
educational interventions such as knowledge and awareness of illness, guided
imagery, and drawings to help the patient achieve full autonomy and confidence
about the perioperative period and surgery. The Hip Injury and Osteoarthritis
Outcome Score (HOOS), Tampa Scale Kinesiophobia (TSK) questionnaire, and Numeric
Rating Scale 0-10 have been used to test the efficacy of IARA. The main finding
in the present study was the effectiveness of IARA model in improving indexes of
pain (p < 0.01) and QoL (p < 0.01) and to keep kinesiophobia levels low in
patients undergoing THA.
PMID- 29944001
TI - Protective and antioxidant effects of copper-nicotinate complex against glycerol
induced nephrotoxicity in rats.
AB - Copper-nicotinate complex (CNC) has antioxidant activities through scavenging of
free radicals formed inside the body. CNC also has anti-tumor and anti
inflammatory activities. The current study was designed to determine the effect
of glycerol on rat kidney function and oxidative stress as well as, the potential
nephroprotective effects of CNC. Forty male Wistar rats were randomly allocated
into four equal groups. The groups of rats were as follows: GI was kept under
normal control conditions; GII was orally given CNC at a dose of 0.043 mg kg-1
body weight (BW), three times/week for 4 weeks; GIII was administered glycerol
(topical application) at a dose of 3.15 ml kg-1 BW daily for 4 weeks; and GIV was
given CNC and glycerol with the same dose and route. The results revealed that
CNC improves the renal dysfunctions induced by glycerol by recovering the levels
of urea and creatinine to normal, as well as through the antioxidant status
manifested by the normalization of catalase, superoxide dismutase, reduced
glutathione, and malondialdehyde levels. Moreover, by its effect as an anti
oxidant, CNC reduces the effect of glycerol on the kidney by decreasing the
fibrosis, degenerative changes and necrotic changes in the renal tubules. In
conclusion, CNC could alleviate the side effects that might be caused by
glycerol.
PMID- 29944002
TI - Decomposing the effect of adiposity on cardiovascular disease - lessons learned
from mediation analysis and relevance for public health.
PMID- 29944003
TI - Evaluating a stroke-specific version of the Illness Perception Questionnaire
Revised, using the Think-Aloud method.
AB - The main purpose was to evaluate, using the Think-Aloud method, a version of the
Illness Perception Questionnaire-Revised for stroke survivors. Six stroke
survivors (mean age = 58.8 years, range = 31-78 years, standard deviation = 18.9
years) took part in Think-Aloud interviews, analysed according to established
guidelines. Overall, 179 problems emerged. The most noteworthy was missing or
insufficient Think-Aloud data generated, where participants did not think out
loud. Others included complex and negative item wording, and items on the
treatment control sub-scale. Questionnaire length, simpler wording and verbal
probing are important considerations in further development of an Illness
Perception Questionnaire-Revised for stroke survivors.
PMID- 29944004
TI - Tapping the resources of Tibetan medicine for the prevention of heart disease.
PMID- 29944005
TI - EuroPrevent 2018, cardiovascular prevention at its highest levels.
PMID- 29944006
TI - Socio-ecological determinants of alcohol, tobacco, and drug use behavior of
adolescents in Kilifi County at the Kenyan coast.
AB - Alcohol, tobacco, and other drug use form a risk factor for health and social
problems during adolescence. From a socio-ecological model, perceptions of 85
young people and 10 stakeholders on the types of alcohol, tobacco, and other
drugs used and the predisposing and protective factors were explored; among
adolescents at the Kenyan Coast in the Kilifi County. We found that the
consumption of home-brewed alcohol, tobacco and marijuana smoking, and khat
chewing was common and requires multi-component and community-centered
intervention. Countering alcohol, tobacco, and other drug use needs enforcement
of strong measures to regulate access to alcohol, tobacco, and other drugs for
minors; addressing social and cultural norms; strategies for poverty alleviation;
and community empowerment.
PMID- 29944008
TI - Comparative effectiveness from a single-arm trial and real-world data: alectinib
versus ceritinib.
AB - AIM: To compare the overall survival of anaplastic lymphoma kinase-positive non
small-cell lung cancer patients who received alectinib with those who received
ceritinib. MATERIALS & METHODS: Two treatment arms (alectinib [n = 183] and
ceritinib [n = 67]) were extracted from clinical trials and an electronic health
record database, respectively. Propensity scores were applied to balance baseline
characteristics. Kaplan-Meier and multivariate Cox regression were conducted.
RESULTS: After propensity score adjustment, baseline characteristics were
balanced. Alectinib had a prolonged median overall survival (alectinib = 24.3
months and ceritinib = 15.6 months) and lower risk of death (hazard ratio: 0.65;
95% CI: 0.48-0.88). CONCLUSION: Alectinib was associated with prolonged overall
survival versus ceritinib, which is consistent with efficacy evidence from
clinical trials.
PMID- 29944009
TI - Exploring Phenotype-Genotype Correlations Using Interstitial Glucose Results in a
Family With a Glucokinase Mutation.
PMID- 29944007
TI - Bench-to-clinic development of imageable drug-eluting embolization beads: finding
the balance.
AB - This review describes the historical development of an imageable spherical
embolic agent and focuses on work performed in collaboration between
Biocompatibles UK Ltd (a BTG International group company) and the NIH to
demonstrate radiopaque bead utility and bring a commercial offering to market
that meets a clinical need. Various chemistries have been investigated and
multiple prototypes evaluated in search of an optimized product with the right
balance of handling and imaging properties. Herein, we describe the steps taken
in the development of DC Bead LUMITM, the first commercially available radiopaque
drug-eluting bead, ultimately leading to the first human experience of this novel
embolic agent in the treatment of liver tumors.
PMID- 29944010
TI - Strong inverse associations of Mediterranean diet, physical activity and their
combination with cardiovascular disease: The Seguimiento Universidad de Navarra
(SUN) cohort.
AB - Background Inverse associations of the Mediterranean diet (MedDiet) and physical
activity with cardiovascular disease have been previously reported. We
investigated the individual and combined contributions of both to this inverse
association in a Mediterranean cohort. Design We used data from 19,536
participants from a prospective cohort of Spanish university graduates, the
'Seguimiento Universidad de Navarra' (SUN) cohort, followed up between December
1999 and December 2016. Methods Adherence to the MedDiet was obtained from a 136
item validated food-frequency questionnaire and categorized in tertiles using
four previously reported dietary scores. A validated questionnaire assessed the
physical activity levels according to volume, intensity and frequency. Results
Participants were followed up during a median time of 10.4 years. Compared with
the lowest category of adherence to the MedDiet (<=3 in the Mediterranean Diet
Score), higher adherence (6-9 points) was strongly inversely associated with
cardiovascular disease (multivariable adjusted hazard ratio = 0.33; 95%
confidence interval (CI) 0.20-0.55). Also, engaging in an active lifestyle (6-8
points in an eight-item score) compared with low activity (<2 points) was
associated with a reduced risk of incident cardiovascular disease (hazard ratio =
0.43; 95% CI 0.20-0.90). Greater adherence to the MedDiet and engaging in high
levels of active lifestyle showed a 75% relatively reduced risk of cardiovascular
disease (hazard ratio = 0.25; 95% CI 0.13-0.48). Conclusions The combined effect
of adherence to the MedDiet and adopting an active lifestyle showed a synergistic
inverse association with cardiovascular disease risk.
PMID- 29944011
TI - Sense of meaning influences mental functioning in chronic renal patients.
AB - In this preliminary study, we examined whether aspects of spiritual well-being
accounted for mental and physical health-related quality of life in 68 patients
with end-stage renal disease, when controlling for age, type of treatment,
physical symptoms, and worries. Hierarchical multiple regressions showed that
meaning was associated with better mental health, while worry and physical
symptoms also accounted for poor mental health. Faith and peace did not
contribute to mental health. Older age, type of treatment (hemodialysis), and
physical symptoms accounted for poor physical health. Our findings suggest that
clinicians should include spiritual well-being in future interventions for end
stage renal disease patients.
PMID- 29944012
TI - Examining fat talk and self-compassion as distinct motivational processes in
women's eating regulation: A self-determination theory perspective.
AB - This study examined whether pursuing intrinsic versus extrinsic goals was
associated with distinct motivational processes in eating regulation and with
healthy versus unhealthy eating. Path analysis demonstrated that appearance goals
were associated with fat talk, whereas health goals were associated with self
compassion. Fat talk was positively associated with non-self-determined
motivation and unhealthy eating, whereas self-compassion was positively
associated with self-determined motivation and healthy eating, and negatively
associated with unhealthy eating. Findings emphasize the negative effects of
pursuing appearance goals and engaging in fat talk and the benefits of pursuing
health goals and being self-compassionate.
PMID- 29944013
TI - Complex role of IL-23R polymorphisms on ankylosing spondylitis: a meta-analysis.
AB - BACKGROUND: The aim of the meta-analysis was to evaluate the association between
10 widely studied polymorphisms of interleukin-23 receptor gene (IL-23R) and
ankylosing spondylitis (AS). METHODS: A comprehensive literature search,
screening of eligible articles and data extraction was performed independently by
two investigators. Further meta-analysis was conducted with STATA 12.0 software
(Stata Corp.; College Station, TX, USA). The association between IL-23R
polymorphisms and AS was evaluated by odds ratio (OR) and 95% confidence
intervals (95% CI). RESULTS: Twenty-five case-control studies with 8431 cases and
8972 controls were included in this meta-analysis. Quantitative meta-analysis
revealed that minor allele frequency (MAF) of rs1004819, rs1495965, and rs2201841
was significantly higher in the AS group (p value < .001, < .001, = .010,
respectively). MAF of rs10489629, rs11209026, rs11465804, and rs1343151was
significantly lower in the AS group (p value = .002, < .001, = .032, < .001,
respectively). However, there is no significant difference between these two
groups in rs10889677, rs11209032, and rs7517847 frequency (p value = .128, .237,
.131, respectively). CONCLUSIONS: The present study indicates that minor allele
carriers of rs1004819, rs1495965, and rs2201841 are susceptible to AS.
Conversely, minor alleles of rs10489629, rs11209026, rs11465804, and rs1343151
have protective effect on AS.
PMID- 29944014
TI - Contribution of the production for self-consumption to food availability and food
security in households of the rural area of a Brazilian city.
AB - Production for self-consumption can meet the principles of food safety such as
respect for food habits and diversity. The participation of production for self
consumption in food availability was compared to the purchase of food for 30 days
in 79 households (272 inhabitants) of the rural area of a Brazilian city in 2012.
The food security was evaluated by the method "Food energy deficiency in the
domicile" that classified 12.7% of the households as insecure. In all households,
staple foods (rice, pasta, corn, beans, milk, eggs, meats) were available and
more than 60% had processed foods (cookies, soft drinks). Only 22.7% of the
calories came from production for own consumption and the biggest expense was the
purchase of carbohydrates (91.1%), mainly sugar (12.2%). Evaluating only the
energy availability of food is not sufficient since the quality and origin of
food is of great relevance in the food security condition.
PMID- 29944016
TI - Impact of the level of sickness on higher mortality in emergency medical
admissions to hospital at weekends.
AB - Objective Routine administrative data have been used to show that patients
admitted to hospitals over the weekend appear to have a higher mortality compared
to weekday admissions. Such data do not take the severity of sickness of a
patient on admission into account. Our aim was to incorporate a standardized
vital signs physiological-based measure of sickness known as the National Early
Warning Score to investigate if weekend admissions are: sicker as measured by
their index National Early Warning Score; have an increased mortality; and
experience longer delays in the recording of their index National Early Warning
Score. Methods We extracted details of all adult emergency medical admissions
during 2014 from hospital databases and linked these with electronic National
Early Warning Score data in four acute hospitals. We analysed 47,117 emergency
admissions after excluding 1657 records, where National Early Warning Score was
missing or the first (index) National Early Warning Score was recorded outside +/
24 h of the admission time. Results Emergency medical admissions at the weekend
had higher index National Early Warning Score (weekend: 2.53 vs. weekday: 2.30, p
< 0.001) with a higher mortality (weekend: 706/11,332 6.23% vs. weekday:
2039/35,785 5.70%; odds ratio = 1.10, 95% CI 1.01 to 1.20, p = 0.04) which was no
longer seen after adjusting for the index National Early Warning Score (odds
ratio = 0.99, 95% CI 0.90 to 1.09, p = 0.87). Index National Early Warning Score
was recorded sooner (-0.45 h, 95% CI -0.52 to -0.38, p < 0.001) for weekend
admissions. Conclusions Emergency medical admissions at the weekend with
electronic National Early Warning Score recorded within 24 h are sicker, have
earlier clinical assessments, and after adjusting for the severity of their
sickness, do not appear to have a higher mortality compared to weekday
admissions. A larger definitive study to confirm these findings is needed.
PMID- 29944015
TI - Novel coumarin-6-sulfonamides as apoptotic anti-proliferative agents: synthesis,
in vitro biological evaluation, and QSAR studies.
AB - Herein, we report the synthesis of different novel sets of coumarin-6-sulfonamide
derivatives bearing different functionalities (4a, b, 8a-d, 11a-d, 13a, b, and
15a-c), and in vitro evaluation of their growth inhibitory activity towards the
proliferation of three cancer cell lines; HepG2 (hepatocellular carcinoma), MCF-7
(breast cancer), and Caco-2 (colon cancer). HepG2 cells were the most sensitive
cells to the influence of the target coumarins. Compounds 13a and 15a emerged as
the most active members against HepG2 cells (IC50 = 3.48 +/- 0.28 and 5.03 +/-
0.39 uM, respectively). Compounds 13a and 15a were able to induce apoptosis in
HepG2 cells, as assured by the upregulation of the Bax and downregulation of the
Bcl-2, besides boosting caspase-3 levels. Besides, compound 13a induced a
significant increase in the percentage of cells at Pre-G1 by 6.4-folds, with
concurrent significant arrest in the G2-M phase by 5.4-folds compared to control.
Also, 13a displayed significant increase in the percentage of annexin V-FITC
positive apoptotic cells from 1.75-13.76%. Moreover, QSAR models were established
to explore the structural requirements controlling the anti-proliferative
activities.
PMID- 29944017
TI - The pluripotency network in colorectal cancer pathogenesis and prognosis: an
update.
AB - Stemness characteristics are defining properties of cancer initiating cells and
are associated with the ability to metastasize and survive in hostile
environments. Establishment of the stem cell network depends on the action of a
set of core transcription factors that work in concert with other ancillary
proteins that are also important during embryonic development. New data
consolidate the role of core pluripotency transcription factors OCT4, SOX2 and
NANOG as adverse prognostic factors in colorectal cancer. mRNA-binding proteins
LIN28 and Musashi, that are associated with stemness, and epigenetic modifiers
such as de-acetylase SIRT1 may also have prognostic value in colorectal cancer.
This paper provides an update of the stem cell factors in the pathogenesis and
prognosis of colorectal cancer.
PMID- 29944018
TI - Exogenous IL-9 Ameliorates Experimental Autoimmune Myasthenia Gravis Symptoms in
Rats.
AB - Interleukin-9 (IL-9) is a multifunctional cytokine involved in protective
immunity or immunopathology depending on the microenvironment and specific
disease settings. Our early study determined that IL-9 and Th9 cells participate
in and promote the progression of experimental autoimmune myasthenia gravis
(EAMG). The data from this study showed that exogenous recombinant rat IL-9 (rrIL
9) acted as an IL-9 receptor antagonist, reduced the incidence of EAMG in rats,
alleviated the severity of the disease, and reduced the anti-acetylcholine
receptor (AChR) IgG antibody levels by altering the Th-subset distribution. These
data suggest that administration of rrIL-9 may provide a novel therapeutic
strategy against MG or related autoimmune diseases. Abbreviations: 2
Mercaptoethanol (2-ME); antibodies (Abs); ?-bungarotoxin (?-BTX); acetylcholine
receptor (AChR); airway hyper-reactivity (AHR); allophycocyanin-conjugated (APC);
antigen presenting cells (APCs); complete Freund's adjuvant (CFA); Cyanine dye 3
(Cy3); dendritic cells (DCs); experimental autoimmune encephalomyelitis (EAE);
experimental autoimmune myasthenia gravis (EAMG); flow cytometry (FACS); fetal
bovine serum (FBS); fetal calf serum (FCS); Fluorescein isothiocyanate (FITC);
gamma chain (?c); intraperitoneally (i.p.); Incomplete Freund's adjuvant (IFA);
interferon (IFN); immunoglobulin (Ig); Interleukin (IL); Janus kinase (JAK);
myasthenia gravis (MG); Mononuclear cells (MNC); neuromuscular junctions (NMJ);
optical density (OD); ovalbumin (OVA); phosphate-buffered saline (PBS);
phycoerythrin (PE); Peridinin chlorophyll protein complex (Percp); Rat AChR ?
subunit (R-AChR97-116); Recombinant Rat (rr); room temperature (RT); signal
transducer and activator of transcription (STAT); T helper cells (Th).
PMID- 29944020
TI - Response to: Prevalence of depressive symptoms among medical students taught
using problem-based learning versus traditional methods.
PMID- 29944019
TI - Epstein-Barr Virus-Associated Nodal Marginal Zone Lymphoma: Part of the Spectrum
of Posttransplant Lymphoproliferative Disorder?
AB - A 56-year-old man, who received deceased kidney transplant 20 years ago,
presented with an enlarged submandibular lymph node. Histologic examination
revealed nodal marginal zone lymphoma in which the neoplastic lymphoid cells
showed diffuse positivity for Epstein-Barr virus early RNA by in situ
hybridization. Systemic lymphoma workup showed stage I disease. The tumor was
managed as a posttransplant lymphoproliferative disorder and the
immunosuppression was modified. There was no evidence of lymphoma at follow-up 6
years after excision alone. This case supports the inclusion of Epstein-Barr
virus-positive nodal marginal zone lymphoma as a form of monomorphic B-cell
lymphoproliferative disorder, in line with the status of its extranodal mucosa
associated lymphoid tissue lymphoma counterpart.
PMID- 29944021
TI - Twelve tips for teaching empathy using simulated patients.
AB - Empathy is a key component of humane, patient-centered consulting. Physician
empathy increases patient satisfaction and enablement; it may even lead to better
health outcomes. Despite this, empathy in clinical encounters is often lacking
and empathy in medical students decreases as they progress from the early to the
senior undergraduate years. The components of empathy - like attentive listening
and a mastery of non-verbal communication - are standard fare for communication
training and universities and clinical postgraduate programs frequently employ
simulated/standardized patients (SPs) to facilitate this training. In the field
of empathy, SPs bring added value to feedback given that many are professional
actors, well versed in the skills of putting themselves "in another character's
shoes." Drawing from the existing evidence base and their personal training and
role-play experience, the authors provide 12 practical tips for teaching empathy
with simulated patients.
PMID- 29944022
TI - Medical Teacher In Ten Minutes.
PMID- 29944023
TI - Are Upfront Levels for Colon "Polyps" Necessary? A Pragmatic Review.
AB - INTRODUCTION: Colon biopsies are among the most frequently examined specimens by
pathologists. Many pathology practices, ours included, review upfront levels on
all gastrointestinal biopsies. In our experience, when a lesion is present on
specimens labeled "colon polyp," it is readily identified on the first level. To
test our hypothesis, we re-reviewed 500 cases in which a lesion was identified
histologically and determined if the diagnosis could be made on the first level.
Furthermore, we examined 50 additional cases of high-grade dysplasia/carcinoma to
determine if the higher-grade component was also present on the first level.
MATERIALS AND METHODS: Cases were retrieved for lesions that could account for a
colon polyp clinically, and the first level was examined to determine if lesional
tissue was present on the first level. Fifty additional cases of higher-grade
lesions were included to ensure higher-grade lesions were present on the first
level. RESULTS: Overall, 497/500 (99.4%) of the non-high-grade lesions were
present on the first level, whereas 3/500 (0.6%) required the additional level
for diagnosis. All 50 high-grade lesions were present on the first level
examined. DISCUSSION: Many pathology practices routinely order upfront levels on
all gastrointestinal biopsies, often generating 2 or 3 slides. Additional slides
increase costs, increase the likelihood of laboratory-generated errors, and can
waste limited tissue on small biopsies for which ancillary studies may be
necessary. Our study showed that a single level is sufficient in the overwhelming
majority of cases in which a lesion is identified histologically.
PMID- 29944024
TI - Maintaining therapeutic progress in multiple myeloma by integrating genetic and
biological advances into the clinic.
AB - INTRODUCTION: Utilizing advances in genetic and immunologic analysis to segment
and direct treatment is potentially a way of maintaining therapeutic progress
toward cure in multiple myeloma (MM). This approach works well using clinical
segments but can be optimized using recent genetic and immunologic technologies,
which have opened the possibility of enhancing risk stratification and disease
subclassification. Areas covered: This position paper discusses strategies to
segment myeloma into subgroups with distinct risk profiles and distinct
targetable lesions are presented. Expert commentary: Risk stratified treatment of
MM is already a clinical reality that can be enhanced by the developmental of
unified segmentation and testing approaches. Mutation-targeted treatment has
proven to be effective against the RAS pathway, but is compromised by intra
clonal and spatiotemporal heterogeneity. Identifying new disease segments based
on tumor biology or immunological content of the microenvironment offers an
exciting new way to control and even eradicate myeloma clones. Going forward,
risk and biologically stratified therapy for myeloma is a promising way of
maintaining therapeutic progress, as is precision immunotherapy directed by the
cellular context of the bone marrow.
PMID- 29944025
TI - Twelve tips to maximize the value of a clinical competency committee in
postgraduate medical education.
AB - Medical education has shifted to a competency-based paradigm, leading to calls
for improved learner assessment methods and validity evidence for how assessment
data are interpreted. Clinical competency committees (CCCs) use the collective
input of multiple people to improve the validity and reliability of decisions
made and actions taken based on assessment data. Significant heterogeneity in CCC
structure and function exists across postgraduate medical education programs and
specialties, and while there is no "one-size-fits-all" approach, there are ways
to maximize value for learners and programs. This paper collates available
evidence and the authors' experiences to provide practical tips on CCC purpose,
membership, processes, and outputs. These tips can benefit programs looking to
start a CCC and those that are improving their current CCC processes.
PMID- 29944026
TI - Radiation risk amongst orthopaedic surgeons - Do we know the risk?
AB - Radiation risk amongst orthopaedic surgeons and theatre personnel is increasing
with increased use of fluoroscopy imaging. Increased radiation risk has been
shown to be associated with an increased risk of malignancies, ocular and thyroid
disorders. Very high exposures have been reported in spinal surgery and during
intra-medullary nailing. With an increase in modern and percutaneous methods, the
use of intra-operative fluoroscopy has increased as well. The aim of this article
was to review the available evidence of radiation risk amongst healthcare
personnel. A systematic search was carried out in PubMED, CINAHL and Cochrane on
intra-operative radiation in trauma and orthopaedic operating room. Inclusion
criteria were clinical studies and systematic reviews reporting on radiation
exposure, fluoroscopy time and references to specific safety guidelines. This
article highlights the safety aspects of radiation protection and harmful effects
of radiation during orthopaedic procedures. The responsibility to minimise
radiation exposure in operating theatre lies with the team within the operating
room.
PMID- 29944027
TI - Hair extensions need to be considered during preoperative assessment.
AB - Hair extensions are an increasingly common hairstyling practice. Others have
demonstrated these devices can lead to hair and scalp injuries. We describe a
recent case where such an injury was narrowly avoided in a patient undergoing a
long surgical procedure. We suggest that preoperative assessment procedures need
to be aware of such devices and provide advice to patients accordingly.
PMID- 29944028
TI - Assessing pain in children in the perioperative setting.
AB - Pain assessment and management in children is challenging for a number of
reasons. This paper aims to identify these challenges and highlight strategies
for effective pain assessment and management in children in the perioperative
setting.
PMID- 29944029
TI - Scapular muscle balance and spinal stabilizer recruitment during an inverted row.
AB - Persons with subacromial impingement syndrome (SIS) have an imbalance in scapular
muscle recruitment. To avoid humeral head compression against the coracoacromial
arch during the early stages of rehabilitation, physical therapists recommend
movements targeting scapular retraction, shoulder depression, and arm extension
such as the inverted row (IR) exercise. The purposes of this study were to
describe: (1) scapular balance ratios during an IR and (2) the magnitudes of
recruitment of spinal stabilizer muscles. Scapular muscle balance ratios from 26
healthy participants were calculated from electromyographic (EMG) activity of the
upper trapezius (UTP), lower trapezius (LTP), middle trapezius (MTP), serratus
anterior (SA), posterior deltoid (PD), latissimus dorsi (LD), and biceps brachii
(BB) during an IR on stable and unstable support surfaces. Balance ratios were
obtained by dividing normalized EMG activity of the UTP by the normalized EMG
values from each of the other six muscles. Four median scapular balance ratios
(UTP/MTP, UTP/PD, UTP/LD, and UTP/BB) ranged from 0.9 to 2.2, whereas the UTP/LTP
ratio ranged from 1.6 to 2.2 and the UTP/SA ratio ranged from 1 to 4.7.
Activation of seven muscles promoted safe containment of the humeral head within
the glenoid fossa during the IR in healthy persons and potentially people with
the tendency for development of SIS. Four spinal stabilizer muscles were
examined: longissimus thoracis (LT), multifidus (MF), rectus abdominis (RA), and
external oblique (EO). Spinal stabilizer EMG activation values ranged from 34% to
40% maximum voluntary isometric contraction (MVIC) for the RA and EO and from 54%
to 66% MVIC for the LT and MF.
PMID- 29944030
TI - Evanescence of Endometrial Carcinomas in Hysterectomy Specimens: Observations on
the "Vanishing Cancer" Phenomenon.
AB - BACKGROUND: The phenomenon of vanishing carcinomas, first described in context of
prostatic carcinomas, has been documented in endometrial carcinomas as well.
METHODS: The archives of the department were searched for case files of
endometrial carcinoma diagnosed on endometrial curetting/biopsy but which did not
reveal any cancer on the subsequent hysterectomy specimen. Clinical and
pathological correlation was established. RESULTS: A total of 5 cases were
retrieved with biopsy-diagnosed endometrial carcinomas, 4 endometrioid and 1
serous type, which on subsequent hysterectomies did not reveal any tumor. These 5
cases represented 1.56% of total hysterectomies in our series. All were Stage Ia
tumors, which on follow-up (mean = 18.2 months) did not show any local
reoccurrence. Adjuvant therapy was instituted in 1 case in the form of pelvic
irradiation in view of the serous histology. In all cases, the primary diagnosis
was reconfirmed and any remote possibility of incorrect patient identification,
laboratory errors, and institution of hormonal therapy were adequately ruled out
along with an extensive endometrial sampling in hysterectomy. CONCLUSION: The
recognition of "vanishing endometrial carcinoma" as a distinct entity is of
utmost importance to avoid mislabeling them as medical errors.
PMID- 29944031
TI - Telehealth requires expansion of physicians' communication competencies training.
AB - We are in the midst of transformation of health systems where remote consulting
(via video, telephone, email, and mobile messaging) is soon to become the
dominant mode of consultation. Most of the literature on telehealth omits
mentioning the need for telehealth communication competencies. Yet evidence base
has been growing about how critical this training is - whether from clinical
communication research or litigation claims analysis. In this article, we are
calling for an urgent expansion of communication skills curricula to encompass
these new telehealth domains from medical schools, specialty trainings to CMEs.
PMID- 29944032
TI - Co-use of cannabis, tobacco, and alcohol during adolescence: policy and
regulatory implications.
AB - Legislative reforms have legalized use of cannabis for medical and recreational
purposes. Efforts to evaluate the public health impact of these changes have
predominantly focused on determining whether liberalizing cannabis policies has
increased cannabis use patterns. Co-use of cannabis and other licit substances,
namely tobacco and alcohol, is common during the developmental period of
adolescence, which is generally characterized by an increase in risk-taking and
novelty-seeking. However, limited research has sought to evaluate the potential
implications of reforms to medical and recreational cannabis laws on concurrent
and simultaneous use of cannabis, tobacco, and alcohol during adolescence. The
current report reviews the extant literature detailing the prevalence and
outcomes associated with concurrent and simultaneous cannabis-tobacco and
cannabis-alcohol use, including recent work that has examined how concurrent and
simultaneous use may be influenced by cannabis reform. This review details how
the cannabis landscape and cannabis retail marketplace have evolved and briefly
summarizes the corresponding policy and regulatory challenges that have emerged.
The report concludes with a focused cannabis co-use research agenda that adopts
different strategies including behavioural economic, self-administration, and
survey research methods.
PMID- 29944033
TI - Haptic Exploratory Procedures of Children and Youth with and without Cerebral
Palsy.
AB - AIMS: Compare haptic exploratory procedures (EPs) and exploratory movements (EMs)
of children. This study also tested the interrater reliability of a novel digital
recording method. METHODS: Participants were 31 children with typical development
(TD) (aged 6 years 1 month to 15 years 9 months; 14 male) and 23 children with
spastic unilateral cerebral palsy (CP) (aged 6 years to 15 years 5 months; 13
males; right hemiplegia, n = 12). RESULTS: There were no statistically
significant differences between groups for expected EP (p = .15), additional EPs
(p = .78), or EMs (p = .69) but there was for mean duration of exploration (p <
.001) and accuracy (p < .001). This suggests that although children with CP
performed similar haptic EPs for each object as children with TD, they took more
time and were less accurate in their identification. There was substantial
agreement between the two raters' observations of expected EP, kappa = .64, p <
.0005. CONCLUSION: Children with CP performed similar haptic EPs as their TD
peers. However, despite similarities, the results indicate that for children with
CP manual ability was not the primary determinant of accuracy or speed of
identification. This study provides evidence for a reliable method of recording
haptic EPs.
PMID- 29944034
TI - Epithelioid Angiosarcoma: An Unusual Cause of Gastrointestinal Bleeding.
PMID- 29944035
TI - Grappling with complexity: Medical students' reflective writings about
challenging patient encounters as a window into professional identity formation.
AB - AIM: Clerkship-specific interactive reflective writing (IRW)-enhanced reflection
may enhance professional identity formation (PIF), a fundamental goal of medical
education. PIF process as revealed in students? reflective writing (RW) has been
understudied. METHODS: The authors developed an IRW curriculum within a Family
Medicine Clerkship (FMC) and analyzed students? reflections about
challenging/difficult patient encounters using immersion-crystallization
qualitative analysis. RESULTS: The qualitative analysis identified 26 unique
emergent themes and five distinct thematic categories (1. Role of emotions, 2.
Role of cognition, 3. Behaviorally responding to situational context, 4. Patient
factors, and 5. External factors) as well as an emergent PIF model from a
directed content analysis. The model describes students? backgrounds, emotions
and previous experiences in medicine merging with external factors and processed
during student?patient interactions. The RWs also revealed that processing often
involves polarities (e.g. empathy/lack of empathy or
encouragement/disillusionment) as well as dissonance between idealized visions
and lived reality. CONCLUSIONS: IRW facilitates and ideally supports grappling
with the lived reality of medicine; uncovering a "positive hidden curriculum"
within medical education. The authors propose engaging learners in guided
critical reflection about complex experiences for meaning-making within a safe
learning climate as a valuable way to cultivate reflective, resilient
professionals with "prepared" minds and hearts for inevitable challenges of
healthcare practice.
PMID- 29944036
TI - Pilates-based exercise in the treatment of a patient with persistent low back
pain following transforaminal lumbar interbody fusion.
AB - BACKGROUND: Low back pain (LBP) is the most commonly reported cause of disability
in people under the age of 45 and is estimated to occur in 60-70% of the adult
population in the industrialized world. This case report describes the use of
Pilates-based exercise (PBE) in the physical therapy management of a patient with
persistent chronic low back pain (CLBP) following transforaminal lumbar interbody
fusion. CASE DESCRIPTION: The patient was a 24-year-old female with a 7-year
history of LBP presenting 17 months following surgery. The patient remained with
constant LBP and right hip pain at 8/10 on the Numeric Pain Rating Scale (NPRS)
after completing a course of physical therapy following the lumbar fusion.
OUTCOMES: The PBE intervention lasted for 22 sessions during which the patient
demonstrated complete resolution of right hip pain and remained with intermittent
LBP (2/10 NPRS) at discharge. Minimally Clinically Important Difference levels
for all self-reported outcome measure instruments were exceeded at discharge. The
patient returned to work with lifting restrictions. DISCUSSION: Patients
following spine surgery are often excluded in studies of spine stabilization and
PBE interventions. This case report describes the use of PBE in the treatment of
a patient following spine fusion. Research to elucidate the impact of PBE on
patients with CLBP is needed.
PMID- 29944037
TI - The anti-inflammation effect of Baige capsule and its principal components
mixture in MCAO rats.
AB - BACKGROUND: Baige (BG) is a compound Chinese herbal preparation, constituted of
different position extracts (ethanol extracts from Pueraria lobate and SFE-CO2
extracts from Radix Angelicae dahuricae) of P. lobata and A. dahurica to treat
the brain injury in patients. AIM: The goal of this study was to identify the
neuroprotective properties of BG and its principal component mixture (PCM) and
verify whether the material basis for BG is its PCM. METHODS: Middle cerebral
artery occlusion (MCAO) was operated on male Sprague-Dawley rat for 2 h,
different doses of BG or PCM or vehicle were gavaged after 3 h of MCAO. Rats were
sacrificed after 30 days treatment. Blood serum inflammation factors and NGF were
detected by ELISA. RESULTS: After 30 days of treatment, both BG and PCM
interventions reduced the infarct volume, modified neurological severity score
(mNSS) in rats, declined IL-1beta and IL-6 levels in the serum, increased NGF
level in the serum and recovered the number of Nissl body in injured brain.
CONCLUSIONS: Both BG and PCM exert equivalent levels of recovery effect in MCAO
on rats; and PCM is the material foundation of BG. This recovery effect is
associated with inflammatory inhibition and NGF production.
PMID- 29944038
TI - Predictors of physical therapists' intentions to counsel for smoking cessation:
Implications for practice and professional education.
AB - OBJECTIVE: This study explored factors predicting intention (predominant
construct in social cognitive behavioral models) for smoking cessation (SC)
counseling that may provide salient information for designing/targeting SC
counseling training for physical therapists (PTs). DESIGN: Cross-sectional
questionnaire survey of PTs licensed to practice in Canada. METHODS: Self
efficacy items and PT views were assessed for internal consistency (Cronbach's
alpha) and data reduced using principal axis factor analysis. Hierarchical linear
regression modeling assessed predictors of intention to counsel for SC. RESULTS:
Internal consistency: self-efficacy and PT views: r = 0.937, r = 0.821,
respectively. Factor structures from self-efficacy: "skills and knowledge" and
"clinic incidentals" (57% total variance); from PT views': "professional role"
and "role modeling" (63.8% total variance). Significant predictors of intent to
counsel for SC were "professional role" (beta = 0.54, p <= 0.001), and "skills
and knowledge" (beta = 0.23, p <= 0.001). CONCLUSIONS: Physical therapists'
intent to engage in SC counseling increases when they consider it their
"professional role." Encouraging PTs to view SC counseling as a professional role
as well as increasing SC counseling self-efficacy focusing on skills and
knowledge to do so needs to be incorporated into entry-level academic physical
therapy programs and continuing professional PT education.
PMID- 29944039
TI - Autologous stem cell transplant in acute lymphoblastic leukemia: prognostic
impact of pre-transplant minimal residual disease.
PMID- 29944040
TI - Mirenas against malignancy: an alternative to operative management.
AB - BACKGROUND: Complex atypical hyperplasia is a recognised precursor to endometrial
cancer, the most common gynaecological cancer of the Western World, with
hysterectomy being the first line of management. With the increasing elderly
population size and BMI, optimal surgical management can be challenging in a sub
set of patients. Levonorgestrol releasing IUS system (Mirena coil) has been
identified as a treatment for those unsuitable for surgical management. AIMS: To
assess the efficacy of Mirena coils in the treatment of endometrial cancers and
complex atypical hyperplasia in our patient population. METHOD: Retrospective
analysis of all type 1 endometrial cancers and CAH diagnosed in Tayside from
April 2011 to March 2016 (duration 5 years) managed by a Mirena coil. Primary
outcome was resolution of malignancy on biopsy. Secondary outcome was
continuation of treatment. RESULTS: Two hundred nineteen out of 245 eligible
endometrial cancers and 38 of 41 CAH case notes were available for assessment. A
Mirena coil was the primary mode of treatment in eight endometrial cancers (3.6%)
and 18 cases of CAH (47.4%). Of the eight endometrial cancers treated, five (62%)
continued with the Mirena coil as the primary mode of treatment. Two patients
died during their follow-up due to unrelated illnesses and one patient proceeded
to hysterectomy due to the absence of progestogenic effect on repeat Pipelle
biopsy at six months (12.5%). Four patients have been followed for one year and
of those; two showed no evidence of malignancy, one was unable to be biopsied and
the last showed persistent disease but was too frail for intervention. At two
year follow-up, two patients remain with one showing disease recurrence. Thirteen
patients (87%) have continued to use the Mirena as management of CAH out of 18
treatments. Of the five patients who did not continue with the IUS; two patients
had progressive disease, despite the coil (11%), two patients lost enough weight
to proceed to hysterectomy and one patient died unexpectedly. Medical co
morbidities and BMI were the main cited reasons for proceeding with the IUS as
the primary treatment. Average BMI of endometrial cancer cases was 43.9 and 45.1
for CAH. CONCLUSIONS: Mirena coil is effective in treating or controlling the
progression of endometrial malignancy in the subgroup of patients where there is
an increased risk associated with definitive surgery. The treatment failure rate
appears to be consistent at about one-tenth of the cohort of women with both
endometrial cancers and complex atypical hyperplasia.
PMID- 29944041
TI - An audit of Ninewells Hospital fertility preservation service.
AB - BACKGROUND: Infertility is a devastating consequence of some medical and surgical
interventions. Men can protect their fertility by storing or 'banking' sperm
before beginning treatment. This is called fertility preservation. Fertility
preservation is traditionally offered to cancer patients undergoing gonadotoxic
therapy. AIMS: This study reports the results of an audit of the Ninewells
Hospital fertility preservation service. It aims to characterise the patients who
attended our service and assess their utilisation rate and outcome of treatment.
METHOD: A retrospective study carried out between January 2000 and March 2017.
Data was collected using a combination of laboratory and clinical records.
RESULTS: A total of 296 patients attended for fertility preservation, of which
264 banked sperm. The number of men referred for sperm banking increased during
the study period from 3 in 2000 to 26 in 2016. Testicular cancer (41.7%) was the
most common indication followed by, haematological malignancies (33.0%), other
malignancies (15.2%) and benign disease (10.2%). The proportion of men with
benign disease increased over-time and accounted for 15% of all patients since
2015. At the time of sperm banking, the median age was 29.8 years. Fourteen men
(5.3%) returned for fertility treatment with their banked sperm after an average
of 40.8 months. After a total of 32 treatment cycles, 12 babies were born (6
singletons and 3 twins). Eight of the fourteen couples succeeded in having at
least one child (57.1%). A small proportion of men engaged in fertility
monitoring (9.5%) or disposed of their banked sperm (5.7%). CONCLUSIONS: There is
an increasing demand for fertility preservation, especially from patients with
benign disease. Only a small proportion of men utilised their banked sperm,
however, those that did had a good chance of becoming fathers. Data from this
study will be used to review our referral pathways and inform our future
practice.
PMID- 29944042
TI - Small bowel evisceration: a late complication following vaginal hysterectomy.
AB - : We present a case of small bowel evisceration occurring as a late complication
following vaginal hysterectomy and subsequent vault prolapse. CASE HISTORY: A 92
year-old female presented with sudden onset severe abdominal pain, followed by
the sensation of vaginal fullness and the discovery of a large prolapse per
vagina, with no history of trauma or sexual intercourse. Past medical history
consisted of vaginal hysterectomy 20 years previously with a subsequent
sacrospinous vault fixation. On examination, a vaginal vault prolapse was found
with 3 feet of oedematous small bowel prolapsed through it. Peristalsis remained
visible. An emergency laparotomy was undertaken as a joint procedure between the
gynaecology and general surgery teams. The small bowel was gently manipulated
back through a 3 cm defect in the vault. Once in the abdomen, it was found to be
viable and no resection was required. The vault defect was closed with 1/0 Vicryl
and the vault was then fixed to the left lateral side wall of the peritoneum.
Routine closure of the abdomen was performed after saline washout. Recovery was
complicated by a postoperative ileus requiring nasogastric tube insertion for two
days. She recovered well following this and will be followed up in the
gynaecology outpatient clinic. DISCUSSION: Small bowel evisceration is a rare
complication following hysterectomy. With relatively few cases reported in the
literature, incidence is difficult to determine. The most commonly reported risk
factors are postmenopausal atrophy, previous vaginal surgery and enterocele.
Cases have been reported following both abdominal and vaginal surgical
approaches, and are commonly precipitated by sexual intercourse, introduction of
a foreign body into the vagina or increased intra-abdominal pressure (Gandhi and
Jha 2011 ). Vaginal evisceration is a gynaecological emergency. Prompt
recognition is vital in order to prevent compromise of intra-abdominal contents
(Codd et al. 2010 ). Management requires a multidisciplinary approach and early
transfer to theatre for urgent surgical repair; various different approaches have
been described, however, if there is any question about organ viability
exploration via a midline laparotomy is indicated (Gandhi and Jha 2011 ).
Educational message/learning point: We have presented this case in order to raise
awareness of small bowel evisceration as a late complication following
hysterectomy. Clinicians in both general surgery and gynaecology should be aware
of its potentially non-specific presenting symptoms, as eviscerated organs may
not be particularly evident on admission. This is a life threatening condition
that requires immediate recognition and management via a multidisciplinary
approach.
PMID- 29944043
TI - A systematic review of the use, quality and effects of pelvic examination in
primary care for the detection of gynaecological cancer.
AB - AIM: This three part systematic review gathered all the current evidence on the
use, quality and effects of pelvic examination (abdominal palpation, bimanual
vaginal examination +/- visualisation of the cervix) in primary care in
diagnosing gynaecological cancer. Research questions * Do primary care
practitioners perform pelvic examination during the assessment of symptoms, which
are potentially indicative of gynaecological cancer? (RQ1) * What is the quality
of pelvic examination performed in primary care, in terms of technical competence
and interpretation of findings? (RQ2) * Is pelvic examination associated with the
referral of patients with gynaecological cancer, and if so, in what way? (RQ3)
Methods: PRISMA guidelines were followed. MEDLINE, EMBASE and Cochrane databases
were searched using a combination of four terms, their MeSH terms and synonyms:
pelvic examination; primary care; competency and gynaecological cancer. Inclusion
and exclusion criteria were defined. Citation lists of all identified papers were
searched. Two authors (PW and PM or CMB or CB) independently screened titles,
abstracts and the full texts of publications. Data extraction was performed by PW
and duplicated in all papers by a second reviewer (PM, CMB or CB). Paper quality
was assessed using CASP methodology. RESULTS: Nine hundred fifty four references
were identified: 21 met the inclusion criteria: 5 RQ1; 6 RQ2; 10 RQ3. Examination
rates prior to referral were generally low: one paper identified pre-referral PE
in 52% of the patients; remaining papers demonstrated examination in less than
half of the patients with suspicious symptoms. No papers explored GPs' competence
at performing PE directly; but one paper identified 39% of 'clinically
suspicious' cervices referred for colposcopy as having no abnormality. Pre
referral PE was associated with reduced diagnostic delay and early stage
diagnosis. CONCLUSIONS: Pre-referral pelvic examination in symptomatic women
appears to be under-performed, despite urgent suspected cancer referral guideline
recommendation to do so (Healthcare Improvement Scotland 2014 ; National
Institute for Health and Care Excellence 2015 ). While no evidence was found to
confirm GPs' competence for performing PE, there was an association with shorter
diagnostic delay and better outcomes in those women where it was performed.
PMID- 29944044
TI - The use of laser assisted hatching of frozen/thawed embryos versus laser assisted
hatching of fresh embryos in human intracytoplasmic sperm injection.
AB - : Cryopreservation of human embryos has become an essential part of assisted
reproduction. It limits the number of embryo transferred while supernumerary
embryos can be transferred in subsequent cycles, however, it is associated with
zonal hardening, which lowers the success rate in the majority of (ICSI) centres,
associated with decreased implantation rate and clinical pregnancy rates.
Assisted hatching has been used to induce microdissection of the zona pellucida.
Many techniques have been used, such as mechanical, chemical, piezo and laser
techniques. AIM: To compare the efficacy of laser assisted hatching of vitrified
embryos and fresh embryos with regards to implantation rate and clinical
pregnancy rate. STUDY DESIGN: Prospective randomised study. PATIENTS AND METHODS:
One hundred twenty women with fresh embryos scheduled for (ICSI) were randomised
in two groups; laser assisted hatching (LAH) group (test group), containing 60
women and the other is (non LAH) (control group). Second group with 120 women
with frozen embryos were randomised in (LAH group) and (non LAH group). On the
day of embryo transfer, 1.48 MUm Infrared Diode laser, class 1 M, was used in
test group to induce zonal microdissection, the quality and safety of embryos is
assessed morphologically after hatching. On the other hand, the zona of the
control group were left intact. Both clinical pregnancy and implantation rates
were estimated. RESULTS: Laser assisted hatching group had clinical pregnancy and
implantation rates of 38% and 50%, respectively. Non laser assisted hatching
group had lower clinical pregnancy and implantation rates; 30% (p = .442) and 33%
(p = .095), respectively, with no statistically significant difference p < .05.
CONCLUSION: LAH does not improve statistically both pregnancy rate and
implantation rate in fresh embryos. However, there is improvement in both
implantation and pregnancy rate in Vitrified group.
PMID- 29944045
TI - Repeat induction of labour for post-term pregnancy.
AB - BACKGROUND: A previous post-term pregnancy is thought to influence the gestation
of a subsequent pregnancy. Adverse maternal and perinatal outcomes are associated
with post-term pregnancy and routine induction of labour by 42+0 weeks is advised
to reduce these complications. OBJECTIVE: To determine the recurrence rate of a
post-term pregnancy and the need for repeat induction of labour. METHODS: This
observational cohort study featured women with a first and second singleton
pregnancy, based on data recorded in the Aberdeen Maternity and Neonatal Databank
(1986-2012). Term and post-term pregnancies were defined as >=37+0 - 40+6 and
>=41+0 weeks, respectively. The exposure was a post-term pregnancy and the
control a term pregnancy. Logistic regression was used to assess post-term
recurrence and repeat induction of labour. RESULTS: The study population
consisted of 25,669 women with 33% of the women delivering post-term in their
first pregnancy. In these women, the rate of a subsequent post-term pregnancy was
35.7% compared to 18.6% for women with an initial term pregnancy (adjusted odds
ratio (aOR) 2.27, 95% confidence interval (CI) 2.11-2.44). Compared to women who
had spontaneous term deliveries in both pregnancies, women who were induced post
term in the second pregnancy had increased odds of having been induced post-term
in their first pregnancy. The adjusted odds ratio was found to be 6.08 (95% CI
5.30-6.98). CONCLUSIONS: Women with a first post-term pregnancy are less likely
to labour spontaneously and more likely to have a second post-term pregnancy with
a higher risk of repeat induction of labour, than women who have previously
delivered at term. These findings could be useful in the counselling of women
with a previous post-term pregnancy. Given that these women are less likely to
labour spontaneously, the offer of an elective induction could also be considered
to potentially improve maternal and perinatal outcomes.
PMID- 29944046
TI - Hysteroscopic and laparoscopic management of caesarean scar (niche) defects in
symptomatic patients.
AB - INTRODUCTION: Worldwide, rates of caesarean section are rising. The term 'niche'
describes the presence of an hypoechoic area within the myometrium of the lower
uterine segment, reflecting a discontinuation of the myometrium at the site of a
previous caesarean section. A defect in caesarean section scar is associated with
symptoms like abnormal uterine bleeding, infertility and complications in
subsequent pregnancy including: risk of rupture and morbidly adherent placenta.
It can also increase rates of complications during gynaecological procedures:
IUCD insertion, evacuation of retained products of conception, hysteroscopy and
risk of ectopic pregnancy at scar site. AIMS: To assess the use of surgical
techniques to repair niche defects in symptomatic patients, with regards to
operative complications, symptomatic relief, postop lower segment thickness and
fertility. METHODS: Patients were identified between August 2015-March 2017.
INCLUSION CRITERIA: Patients who had one previous caesarean section, symptomatic
i.e. abnormal uterine bleeding, dysmenorrhoea, dyspareunia, infertility.
EXCLUSION CRITERIA: Asymptomatic patients. No previous caesarean section.
RESULTS: Between August 2015 and March 2017, six patients underwent surgical
management of niche defect. Four patients reported post menstrual bleeding, one
patient had infertility and one had intermenstrual bleeding and dyspareunia. All
patients had one caesarean section previously. Mean lower segment measurement
preoperatively was 2.5 mm +/- 1.6 mm. EBL intraoperatively was 130 ml (10-180
ml). Mean operating time was 90 mins (70-150 min). One patient was pregnant after
niche repair and delivered by CS at 38 w. In all six cases, TVS in 3-5 months
after surgery revealed restored lower segment to normal thickness 9.2 mm +/- 1.8
mm. Symptom resolution was noted in all patients. There were no operative
complications. CONCLUSIONS: Anterior uterine wall should be explored in the case
of symptomatic patients with previous caesarean section scar. Hysteroscopic
resection should not be proposed when RMT is <3 mm. Laparoscopic/vaginal repair
allows restoration of the anatomy of the lower uterine segment when residual
myometrium is <3 mm. Laparoscopic repair allows antefixation in cases of
retroverted uterus. Consideration of a surgical approach should be determined by
the patient's plans for fertility and by niche thickness. For women who do not
desire pregnancy and whose niche thickness is >3 mm, a hysteroscopic approach
should be considered. Women with symptomatic caesarean scar defects who do not
desire fertility may also be candidates for hysterectomy. Patients who desire
future fertility, especially those with <3 mm of myometrium at the niche site,
should undergo laparoscopic resection.
PMID- 29944047
TI - The Water@Birth Study: an exploratory study on the requirements of water for hand
hygiene during labour and delivery in low-income countries.
AB - BACKGROUND: Infections acquired during childbirth are one of the leading causes
of maternal death; the majority of these deaths occur in low-income settings.
Hand hygiene is one of the most effective ways of preventing infection but
requires basic resources, such as running water, to be performed. Limited
literature on water volume requirements for hand hygiene in healthcare facilities
exists despite the importance of this information, particularly in resource-poor
settings. AIM: To establish the volume of water required for hand hygiene during
childbirth in low-income countries. METHODS: Data was collected in Aberdeen
Maternity Hospital (AMH) and Felege Hiwot Referral Hospital, Ethiopia (FHRH),
with an average of 14 and 16 deliveries per day respectively. Primary data on
hand hygiene opportunities (HHOs) during childbirth were gathered using
observational methods, and secondary data gathered from register and case-note
reviews. The volume of water required for each HHO (H2O/HHO) was calculated by
multiplying flow rate by hand washing time. Estimates of water requirements were
derived by calculating the number of HHOs during childbirth and the H2O/HHO.
Water requirement estimates from each facility were compared to each other as
well as to WHO recommendations. Due to skewed data, Spearman's rho was utilised
to explore the relationship between variables. RESULTS: Eleven deliveries were
observed in AMH and 20 in FHRH. The number of HHOs was largely determined by the
length of labour. Stringently following WHO recommendations lead to a
significantly higher number of HHOs than was performed in clinical practice at
both sites. Hand washing also occurred for a much shorter time than the WHO
recommendation of 40-60 seconds, with an average of 24 seconds in AMH and 25
seconds in FHRH observed. The estimated number of HHOs at sites ranged from 5 to
16 per hour per delivery and water consumption from 21 to 159.6 litres per hour
per delivery. Hand hygiene was estimated to require 8937.6 litres and 4838.4
litres per day or 638.4 litres and 302.4 litres per delivery for AMH and FHRH,
respectively. CONCLUSIONS: Water requirements are variable due to the nature of
childbirth but are not currently met in low-income countries. In terms of
performance of hand hygiene, there is a large gap between clinical and
recommended practice and thus room for improvement. The volume of water required
for hand hygiene has significant implications for water requirements within
maternity units, particularly in resource-poor settings. Further research on
water requirements is merited to improve the targeting of limited resources.
PMID- 29944048
TI - A document analysis of 'Adverse incidents in fertility clinics: lessons to learn'
reports published by the Human Fertilisation and Embryology Authority between
2010-2015.
AB - BACKGROUND: The fertility clinic is an environment in which significant adverse
incidents are potentially catastrophic. The Human Fertilisation and Embryology
Authority (HFEA) publishes an annual report of adverse incidents in fertility
clinics across the UK. These incident reports are published with the view that
providing clinics with 'lessons to learn' will encourage education, lead to a
reduction in adverse incidents and create a culture of transparency. However, the
latest data demonstrates that a meaningful reduction in adverse incidents in the
fertility sector is yet to be seen. Consequently, the efficacy of the HFEA
incident reporting system is uncertain. Human factors has emerged as a science,
which may be applicable to the incident reporting systems used within the
fertility clinic. Through the application of human factors theory, ergonomists
endeavour to realise how systems can be redesigned to maximise performance and
minimise risk. The HFEA have already recognised the value of applying human
factors science to the complex, sociotechnical system of the fertility clinic in
their latest incident report. METHOD: This study has capitalised on the HFEA's
realisation by conducting a human factors based document analysis of the
published HFEA incident reports, with the aim that the results would inform
recommendations for enhancing the HFEA's current incident reporting system. The
narrative, messages and intentions of each report were analysed using an
inductive thematic analysis. The HFEA's analyses of the adverse incidents, in
particular the contributory factors and learning points identified, were analysed
using a deductive thematic analysis, using the SEIPS model as a conceptual
framework. RESULTS: Firstly, the results of each inductive thematic analysis
revealed four themes, which emerged from the data, giving an insight into the
narrative, messages and intentions of the HFEA reports. The themes were: (1)
culture of incident reporting, (2) role of the HFEA, (3) importance of incident
reporting and (4) incident reporting processes. Secondly, the deductive thematic
analysis revealed that the HFEA do not employ a holistic, systems based approach
to errors which led to underdeveloped analyses of incidents and weaker
interventions. CONCLUSION: The results of this study align with the current
literature, highlighting that incident reporting systems which do not embrace a
more systematic methodology are making a poorer impact. We recommend that the
HFEA strive to fully embed human factors methodologies into their incident
reporting systems. We propose that human factors will enhance the reports and
improve education, learning and corrective actions in fertility clinics.
PMID- 29944049
TI - Novel use of laparoscopic-guided TAP block in total laparoscopic hysterectomy.
AB - BACKGROUND: Transverse abdominis plane (TAP) block is a peripheral nerve block
designed to anaesthetise the nerves supplying the anterolateral abdominal wall
(T6 to L1). We introduced laparoscopic TAP block at Ninewells Hospital in 2014
and present a retrospective study assessing its efficacy. To our knowledge, there
is limited study done on laparoscopic-guided TAP block whilst there are abundant
literatures available on ultrasound-guided TAP block. AIMS: To evaluate the
efficacy of laparoscopic-guided TAP block as postoperative analgesia following
total laparoscopic hysterectomy (TLH). METHODOLOGY: A retrospective study was
done between November 2014 to October 2016 (24 months) comparing patients who had
TLH with TAP block (Group 1; n = 45) and patients who had TLH without TAP block
(Group 2; n = 31) in our gynaecology unit. Patients were identified from theatre
database. Data was collected from clinical portal and medical notes. The data
included demographic information, BMI, METS score, intra-operative opiates use,
post-operative pain scores, opiate requirements and use of patient-controlled
analgesia (PCA), total dose of opiates used and day of discharge. The outcomes
were analysed using means, odds ratios (OR), Mann-Whitney U-test and Fisher's
exact or Chi-square test with 95% confidence interval (CI). RESULTS: Patients in
Group 1 were older (mean age of 64.4, range 38-87) when compared to Group 2 (mean
age of 49.3, range 37-81). Group 1 and 2 had comparable mean BMI (30.34 vs.
30.02) and METS score (6.77 vs. 7.76). Mean post-operative pain scores were lower
in Group 1 within 4 hours, in periods of 4-12 hours, 12-24 hours and 24-48 hours
post-op. Smaller proportion of patients in Group 1 required opiates post
operatively in all periods as compared to Group 2. This was statistically
significant in the periods of 12-24 hours post-op (OR 0.31, 95% CI 0.11-0.82; p =
.01). PCA use was significantly lower in Group 1 (OR 0.02, 95% CI 0.0014-0.46; p
= .01). Group 1 had lower mean total dose of opiates used (27.182 mg, range 0-102
mg) than Group 2 (59.452 mg, range 0-240 mg), which was statistically significant
(p < .0001). Average post-op hospital stay was 1.3 and 1.8 days in Group 1 and 2,
respectively. CONCLUSION: Laparoscopic-guided TAP block delivered as post
operative analgesia following TLH results in reduced opiate requirement at post
operative period 12-24 hours, reduced PCA use and lower total dose of opiates
used.
PMID- 29944050
TI - Review of use of Mysodelle as a method of induction of labour.
AB - BACKGROUND: Mysodelle is a 200 mcg misoprostol, vaginal delivery system. It is a
PGE1 analogue and accepted as a method of IOL by Scottish medicine consortium in
2014 (Medicines Health and Regulatory Authority; Wing et al., 2013 ). AIMS: The
main objective of this project was to determine efficacy of Mysodelle with
regards to time interval between insertions to delivery. We also studied the
safety profile of Mysodelle with regards to operative delivery rates, foetal
concerns and incidence of hyperstimulation. METHODOLOGY: A protocol which
outlined the criteria for suitability for the use of Mysodelle was developed.
This method was used for IOL for primiparous women more than 38 weeks of
gestations with unfavourable cervix and intact membranes with no foetal concerns
on scan, i.e. suboptimal growth or reduced liquor. Mysodelle was left in situ for
maximum duration of 24 hours and CTG was monitored every 4 hours. The data was
collected prospectively over 1 year from January 2016. RESULTS: We reviewed 50
women for the study period of one year. All women were primiparous with singleton
term gestations between 38 + 5 weeks to term +11 days. The indications for IOL
included postdates, reduced foetal movement, big baby and advanced maternal age.
Following the use of Mysodelle, 55% of the women progressed to active labour and
did not require oxytocin on labour ward. In 20% of the women, Mysodelle was
removed for suspicious CTG or tachysystole. Four women failed IOL with Mysodelle.
14% women had hyperstimulation response to Mysodelle and needed terbutaline. 46%
women had spontaneous vaginal delivery and 24% needed instrumental delivery.
Remaining 30% patients delivered by caesarean section. The median time from
Mysodelle administration to vaginal delivery was 21 hours (95% confidence
interval 18.8-26.8 hours). There were no neonatal adverse outcomes. CONCLUSIONS:
Results at AMH overall are in keeping with those from EXPEDITE study (Wing et al.
2013 ). It was found to be more efficacious in terms of insertion to delivery
time, however, was associated with more tachysystole and hyperstimulation
requiring terbutaline as previously highlighted in Cochrane review (Alfirevic and
Weeks 2006 ; Hofmeyr et al. 2010 ). There was no increased risk of operative
delivery or adverse neonatal outcome with the use of Mysodelle. A reduction in
time to vaginal delivery and time to active labour associated with misoprostol
vaginal delivery system may be an advantage for patients and the service (ISD
Scotland 2013 ), but it needs to be seen if this benefit is offset due to
increased requirements for foetal monitoring due to uterine tachysystole and
hyperstimulation. MHRA have advised that Mysodelle can cause uterine
tachysystole, that might not respond to tocolytic treatment. (MHRA medicine
update 2018).
PMID- 29944051
TI - Perinatal outcomes following mid trimester detection of isolated short foetal
femur length.
AB - BACKGROUND: Short foetal femur length (FL) is a normal variant but may also be a
marker for disorders such as skeletal dysplasia, Trisomy 21 (T21), Turners
syndrome, congenital infection (TORCH) and foetal growth restriction (FGR). AIM:
Our aim was to review outcomes in our population following a diagnosis of
isolated short FL (FL <5th centile) when detected at the time of mid trimester
foetal anomaly scan (FAS). METHODS: All women within NHS Tayside who attended for
routine mid trimester foetal anomaly scan at 18-21 weeks gestation (Range = 18+2
21+3 weeks) between November 2011 and June 2016 were included. Those who had an
isolated FL <5th centile were identified using Viewpoint. Data relating to
perinatal and childhood outcomes were obtained from local databases. RESULTS: 72
women were identified. The median maternal age was 30 years (range = 17-45
years). 39/72 (54.2%) women were primigravid. 41/72 (56.9%) women had Down's
syndrome screening (DSS). 12/72 (16.7%) women were offered TORCH screens, none of
which were positive for recent or current infection. Invasive testing was
performed in 8/72 (11%) women; 1 had previously had first trimester chorionic
villus sampling (CVS) for raised maternal age. 7 women had amniocentesis (1 prior
to FAS for increased DSS risk). All those that had invasive testing had normal
foetal karyotype. Median gestational age at delivery was 38 weeks (range = 26-41
weeks). 10/72 (13.9%) had genetic testing after birth, 6 were performed shortly
after birth due to dysmorphic features. 4/72 (5.5%) had Trisomy 21 and 3 of these
had VSD that had not been identified antenatally. For those with T21, 3 mothers
had declined DSS and 1 had a low risk DSS result. Fifty out of seventy two
(69.4%) babies had constitutionally short femurs. 13/72 (18%) had FGR and 3/72
(4.2%) had skeletal dysplasia. One baby had William's syndrome, one had
Klinefelter syndrome and two had genetic deletions of uncertain significance.
CONCLUSIONS: Knowledge of outcomes will enable better counselling for women with
isolated short foetal femur. In our local population, more than two-thirds of the
babies with isolated short femur will be normal. Women must, however, be informed
of the potential for foetal aneuploidy and foetal skeletal dysplasia. In view of
this, women should be offered invasive testing and follow-up ultrasound scans to
assess the foetal skeleton. Furthermore isolated short foetal femur is a marker
for FGR and all women with isolated short femur should be offered serial
ultrasound scans to assess foetal growth and well-being in the third trimester.
PMID- 29944052
TI - Diagnosing causes of headache within the postpartum period.
AB - BACKGROUND: Headache is one of the most common symptoms following delivery and
the underlying cause may be benign or life threatening. Identification of the
cause of headache in the postpartum period can be challenging and relies on a
comprehensive history and thorough examination, with particular focus on the
presence or absence of neurological signs, which may suggest a more serious
diagnosis (Nelson-Piercy 2010 ). However, through clinical experience and
research, we have noted that post-partum headache is significantly under
recognised and treated (Goldszmidt et al. 2005 ). AIMS: To ensure a standardised
approach to the management of patients presenting with postpartum headache, we
sought to introduce a diagnostic tool for postpartum headache. METHODS: This was
a literature review combined with a postpartum headache case example that
occurred within our institution in 2015. Risk factors and potential clinical
failures from the case were noted and compared to the literature. RESULTS: Our
case is a 28-year-old woman who developed a postpartum headache following
spontaneous vaginal delivery. Of note, the patient had an epidural inserted in
labour for analgesia. Initially, systemic and neurological examinations were
normal and the patient was discharged home with simple analgesics and a diagnosis
of tension-type headache. She represented with worsening headache, pyrexia and
signs of meningism. Lumbar puncture confirmed a diagnosis of bacterial meningitis
caused by Haemophilus influenzae. She was treated with IV ceftriaxone and
discharged home without any long-term sequelae. In an attempt to improve
recognition of post-partum headache, especially rare causes such as meningitis,
NHS Tayside has chosen to adopt the PARTUM mneumonic (Lim et al. 2014 ). Pressure
(blood pressure for pre-eclampsia/eclampsia) Anaesthetic (post-dural puncture
headache) Reversible (vasoconstriction syndrome) Thrombosis (cerebral venous
sinus thrombosis, ischaemic stroke) Use your brain (there are so many other
causes of headache) Migraine (Lim et al. 2014 ). PARTUM was first devised in 2014
as part of a research paper published by the Journal Practical Neurology (Lim et
al. 2014 ). The aim of the mnemonic is to allow the treating physician a basic
list of postpartum headache causes to use as a working diagnosis (Lim et al. 2014
). CONCLUSIONS: Research has shown that many postpartum headaches go undiagnosed
and as a result are poorly treated, often returning following discharge from
secondary care (Nelson-Piercy 2010 ). The hope is that the introduction of this
adjuvant will allow clinicians to identify the cause of postpartum headaches
earlier and will allow life threatening diagnoses to be quickly excluded.
PMID- 29944053
TI - Celebrating scholarship in healthcare simulation: Medical teacher turns 40.
PMID- 29944054
TI - Outcome of Isolated Absent Septum Pellucidum Diagnosed by Fetal Magnetic
Resonance Imaging (MRI) Scan.
AB - Improved fetal imaging has resulted in increased diagnosis of isolated absent
septum pellucidum without other intracranial abnormalities. There is little
literature regarding outcomes for these fetuses. This study hypothesized the
majority of infants diagnosed by fetal magnetic resonance imaging (MRI) with
isolated absent septum pellucidum would retain this diagnosis postnatally.
Specifically, in the absence of postnatal endocrine or ophthalmologic
abnormalities, postnatal imaging would find no additional related findings, and
fetuses would be at low risk for developmental delay. Two of 8 subjects met
postnatal criteria for septo-optic dysplasia; remaining subjects had normal
postnatal endocrine and ophthalmologic evaluations and no significant related
findings on postnatal MRI. One subject without septo-optic dysplasia had delays
on developmental screening; all others had normal screening (range of follow-up 8
72 months). Our study questions the necessity of postnatal imaging for prenatally
diagnosed isolated absent septum pellucidum. Majority of fetuses with isolated
absent septum pellucidum retained this diagnosis postnatally.
PMID- 29944055
TI - Evaluation of the relationship between microalbuminuria and 25-(OH) vitamin D
levels in patients with type 2 diabetes mellitus.
AB - BACKGROUND: 25-(OH) vitamin D (VD) deficiency has been described as potential
risk factor for the development of diabetes in many epidemiological studies. 25
(OH) VD deficiency and insulin resistance associated with this deficiency are
common findings in patients with type 2 diabetes mellitus. The objective of this
study is to evaluate the relationship between 25-(OH) VD levels and
microalbuminuria. METHODS: The patients with type 2 diabetes mellitus aged
between 40 and 65 years, who were admitted to the diabetes outpatient clinics of
our hospital, were evaluated in two different groups. The first group consisted
of 119 patients with insufficient 25-(OH) VD levels (10-30 ng/mL) and the second
group consisted of 121 patients with 25-(OH) VD deficiency (<=10 ng/mL). The
relationship between 25-(OH) VD levels and the level of microalbuminuria was
evaluated in the two groups. RESULTS: The mean 25-(OH) VD level was 11.5 ng/mL
and the mean HbA1c level was 9.1%. When the patient groups were evaluated
according to 25-(OH) VD levels, HbA1c values were significantly higher in
patients with a 25-(OH) VD level of 10 ng/mL or lower (p = .039). 25-(OH) VD
levels were not significantly different between patients with different stages of
renal failure (p = .119), whereas the level of microalbuminuria was significantly
different (p = .030). CONCLUSIONS: This study found that the level of
microalbuminuria was significantly higher in patients with 25-(OH) vitamin D
deficiency compared to patients with 25-(OH) VD insufficiency.
PMID- 29944056
TI - Genome Sequences of Three Races of Peronospora effusa: A Resource for Studying
the Evolution of the Spinach Downy Mildew Pathogen.
AB - Downy mildew disease, caused by the obligate oomycete pathogen Peronospora
effusa, is the most important economic constraint for spinach production. Three
races (races 12, 13, and 14) of P. effusa have been sequenced and assembled. The
draft genomes of these three races have been deposited to GenBank and provide
useful resources for dissecting the interaction between the host and the pathogen
and may provide a framework for determining the mechanism by which new races of
the pathogen are rapidly emerging.
PMID- 29944057
TI - Differentiating the Drug Normalization Framework: A Quantitative Assessment of
Cannabis Use Patterns, Accessibility, and Acceptability Attitudes among
University Undergraduates.
AB - BACKGROUND/OBJECTIVES: The drug normalization framework investigates the social
integration of substance use. This article contributes a quantitative assessment
of cannabis normalization as differentiated by social location predictors.
METHODS: Logistic and zero-inflated negative binomial regression models assess
three areas of cannabis normalization: accessibility, acceptability, and recent
use. Peer network cannabis use prevalence, gender, nativity, campus locale and
living arrangement are explored as focal predictors of variation in normalization
among 1,713 cannabis using and nonusing undergraduate students in Canada.
RESULTS: Women report lower odds of positive cannabis acceptability attitudes.
While women report lower rates of recent cannabis use, gender is not a
significant predictor for lifetime prevalence. Being a recent immigrant
significantly predicts lower recent use, lower odds of favorable attitudes to
cannabis, and reduced accessibility in comparison to students born in Canada.
Longer-term immigrants do not show significant differences from students born in
Canada on accessibility and acceptability, suggesting a substance use
acculturation effect. Lower peer cannabis use prevalence exhibits a protective
effect against use. In comparison to students who report that "some" of their
peer network uses cannabis, those with "all" users in their network exhibit lower
acceptability attitudes. This suggests a threshold relationship between peer use
prevalence and acceptability. Conclusions/Importance: This article provides a
data point for assessing future shifts in cannabis normalization prior to
impending changes in Canadian drug policy that will legalize recreational
cannabis use. Results show that normalization components of recent use,
acceptability, and accessibility are differentiated by gender, nativity, and peer
network cannabis use prevalence.
PMID- 29944058
TI - Modulation of transporter activity of OATP1B1 and OATP1B3 by the major active
components of Radix Ophiopogonis.
AB - Radix Ophiopogonis is often an integral part of many traditional Chinese
formulas, such as Shenmai injection used to treat cardio-cerebrovascular
diseases. The present study aimed to investigate the influence of the four active
components of Radix Ophiopogonis on the transport activity of OATP1B1 and
OATP1B3. The uptake of rosuvastatin in OATP1B1-HEK293T cells were stimulated by
methylophiopogonanone A (MA) and ophiopogonin D' (OPD') with EC50 calculated to
be 11.33+/-2.78 and 4.62+/-0.64 MUM, respectively. However, there were no
remarkable influences on rosuvastatin uptake in the presence of
methylophiopogonanone B (MB) or ophiopogonin D (OPD). The uptake of atorvastatin
in OATP1B1-HEK293T cells can be increased by MA, MB, OPD and OPD' with EC50
calculated to be 6.00+/-1.60, 13.64+/-4.07, 10.41+/-1.28 and 3.68+/-0.85 MUM,
respectively. The uptake of rosuvastatin in OATP1B3-HEK293T cells was scarcely
influenced by MA, MB, and OPD, but was considerably increased by OPD' with an
EC50 of 14.95+/-1.62 MUM. However, the uptake of telmisartan in OATP1B3-HEK293T
cells was notably reduced by OPD' with an IC50 of 4.44+/-1.10 MUM, and barely
affected by MA, MB, and OPD. The four active components of Radix Ophiopogonis
affect the transporting activitives of OATP1B1 and OATP1B3 in a substrate
dependent manner.
PMID- 29944059
TI - Cellular adaptive response and regulation of HIF after low dose gamma-radiation
exposure.
AB - PURPOSE: Cellular damage due to low dose of gamma-radiation (<=0.1 Gy) is
generally extrapolated from observing the effects at higher doses. These
estimations are not accurate. This has led to uncertainties while assessing the
radiation risk factors at low doses. Although there are reports on the radiation
induced adaptive response, the mechanism of action is not fully elucidated,
leading to the uncertainties. One of the outcomes of low dose radiation exposure
is believed to be an adaptive response. The mechanism of adaptive response is not
fully understood. Therefore, the study was undertaken to understand the role of
hypoxia inducible factor (HIF) on radiation induced adaptive response. MATERIALS
AND METHODS: Human breast cancer cell line MCF-7 cells pre-exposed to low dose
gamma-radiation (0.1 Gy; priming dose) were exposed to 2 Gy (challenging dose) 8
h after the priming dose and studied for the adaptive response. Cell death was
measured by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT)
assay and apoptosis was measured by fluorescence-activated cell sorting analysis.
DNA damage was measured by alkaline comet assay. HIF transcription activity was
assayed using transiently transfected plasmid having HIF consensus sequence and
luciferase as the reporter gene. RESULTS: Cells when exposed to 0.1 Gy priming
dose 8 h prior to the higher dose (2 Gy; challenging dose) results in lower
amount of radiation induced damages compared to the cells exposed to 2 Gy alone.
Cobalt chloride treatment in place of priming dose also results in the protection
to cells when exposed to challenging dose. There was up-regulation of HIF
activity when cells were exposed to priming dose, indicating the role of HIF in
radiation induced response. CONCLUSION: Results indicate the gamma-radiation
induced adaptive response. One of the mechanism proposed is up-regulation of HIF
after low dose exposure, which protects the cells from damages when they are
exposed to challenging dose of 2 Gy radiation.
PMID- 29944060
TI - The effect of air dust pollution on semen quality and sperm parameters among
infertile men in west of Iran.
AB - BACKGROUND: Pollutants during haze and Asian dust storms are transported out of
the Asian continent, affecting the regional climate and the hydrological and
biogeochemical cycles. Nonetheless, no specific studies evaluated the dust
particles influence on semen quality in a specific geographical area. OBJECTIVE:
In this article, we investigated the effect of dust particles on semen quality
and sperm parameters among infertile men. METHODS: A descriptive-analytic study
was conducted among 850 infertile men between 2011 and 2015 years. Semen quality
was assessed according to the WHO 2010 guidelines, including sperm concentration,
progressive motility, and morphology. Four-year average dust particle
concentrations were estimated at each participant's address using the Air
Pollution Monitoring Station affiliated with the Department of Environment of
Kermanshah city were gathered. RESULTS: Dust particle levels were highest in the
summer months, in Kermanshah province. Our results show that, dust pollution was
found to be significantly negatively correlated with sperm morphology and sperm
concentration before and after lab-processing, but sperm progressive motility is
low sensitive to dust particles. CONCLUSIONS: Our findings showed that exposures
to dust particle may influence sperm quantity in infertile men, consistent with
the knowledge that sperm morphology and concentration are the most sensitive
parameters of dust pollution.
PMID- 29944061
TI - Implementing a Standardized Transition Care Plan in Skilled Nursing Facilities.
AB - Prior studies have not described strategies for implementing transitional care in
skilled nursing facilities (SNFs). As part of the Connect-Home study, we pilot
tested the Transition Plan of Care (TPOC) template, an implementation tool that
SNF staff used to deliver transitional care. A retrospective chart review was
used to describe the impact of the TPOC template on three implementation
outcomes: reach to patients, staff adoption of the template, and staff fidelity
to the intervention protocol for transition care planning. The template reached
100% of eligible patients ( N = 68). Adoption was high, with documentation by
four disciplines in 90.6% of patient records ( N = 61). Fidelity to the
intervention protocol was moderately high, with 73% of documentation that was
concordant with the protocol. Our findings suggest an electronic medical record
(EMR)-based implementation tool may increase the ability of staff to prepare
older adults and their caregivers for self-care at home. Further research is
needed to test the efficacy of the protocol on patient outcomes after transitions
from SNF to home.
PMID- 29944062
TI - Hand grip strength is associated with fatigue among men with COPD:
epidemiological data from northern Sweden.
AB - The aim of this study was to investigate if hand grip strength (HGS) is
associated with: 1) fatigue, and specifically clinically relevant fatigue (CRF);
2) low physical activity; and 3) fatigue independent of physical activity level,
among individuals with and without COPD. Data were collected from the Obstructive
Lung Disease in Northern Sweden (OLIN) COPD-study in 2014. HGS was measured with
a hand-grip dynamometer, fatigue and physical activity were assessed by
questionnaires; FACIT-Fatigue respectively IPAQ. Among individuals with COPD (n =
389), but not without COPD (n = 442), HGS was lower among those with CRF than
those without CRF, significantly so among men (p = 0.001) and close to among
women (p = 0.051). HGS was not associated with physical activity levels within
any of the groups. HGS was associated with fatigue among men, but not women, with
COPD independent of physical activity level, age, height, and smoking habits
(Beta = 0.190, 95% CI 0.061-0.319, respectively Beta = 0.048, 95% CI-0.056
0.152), while there were no corresponding significant findings among individuals
without COPD. In summary, HGS was associated with CRF among individuals with COPD
in this population-based study. Among men with COPD, HGS was associated with
fatigue independent of physical activity level and common confounders.
PMID- 29944063
TI - Medical-Legal Partnership Impact on Parents' Perceived Stress: A Pilot Study.
AB - Stress has adverse effects on health, and prolonged stress exposure is a risk
factor for several mental and physical illnesses. 1 Families living in poverty
face many stressors created and maintained by economic hardship and unaddressed
legal and social needs. Medical-Legal Partnerships (MLPs) aim to improve health
and well-being by addressing health-harming legal and social needs of patients.
This pilot study examined whether MLP-involved parents perceived themselves as
stressed; to what they attributed their stress; and whether they reported a
reduction in stress when their MLP cases were closed. The study shows
improvements in perceived stress following receipt of MLP interventions.
PMID- 29944064
TI - Self-defining memories related to alcohol dependence and their integration in the
construction of the self in a sample of abstinent alcoholics.
AB - Using a self-defining memory task, this work studies the exact moment in which
abstinent alcoholics perceived themselves as addicted. Phenomenological variables
involved in the memory were obtained asking participants to evaluate their
cognitions, perceptions and emotions associated with that self-defining memory.
The sample consisted of 12 female and 31 male ex-alcoholics, with abstinence
ranging from 6 months to 23 years. Mean age was 52.91 years. Our findings showed
that awareness of the alcoholic self emerges in the context of uncontrolled
consumption or an ultimatum from family members. This type of memory had a
positive valence for most of the participants, regardless of the memory
perspective (actor versus spectator). Those who remembered from an actor
perspective, perceived the event as providing higher growth and personal
learning. These results show the importance of exploring situations of
uncontrolled consumption and family dynamics in the self-recognition of alcohol
dependence. In addition, reinforcing an actor perspective compared to a spectator
perspective might results in higher levels of personal enrichment, which may help
maintain a patient's long-term recovery. These results support the use of
autobiographical memory techniques to enhance awareness of the addicted self, and
suggest the need to include these interventions in rehabilitation programmes.
PMID- 29944065
TI - Fatigue Among Adults With Type 1 Diabetes Mellitus and Implications for Self
Management: An Integrative Review.
AB - Purpose The aim of this review was to integrate empirical and theoretical
literature on fatigue among adults with type 1 diabetes mellitus (T1DM). A
methodological review using an integrative approach was used. Databases MEDLINE
via Pubmed, CINAHL, PsycINFO, and Science Direct were searched for peer-reviewed
articles published in English from 2007-2017, using the following search terms
and Boolean operators: "Type 1 Diabetes" and "Fatigue." Of 199 articles initially
retrieved, 14 were chosen for inclusion. These articles included 13 quantitative
(7 cross-sectional, 2 cohort, 2 secondary data analyses, 2 experimental) and 1
qualitative phenomenology. Fatigue was identified as one of the most troublesome
symptoms reported in persons with T1DM. Four main themes emerged: fatigue in T1DM
is multidimensional and related to psychological, physiological, situational, and
sociodemographic factors. Conclusions Fatigue is considered a classic symptom of
hyperglycemia; however, there were minimal data to support the theory that
fatigue is related to hyperglycemia or hypoglycemia. Studies on fatigue among
persons with T1DM are limited to small samples and cross-sectional designs with
few randomized controlled trials addressing fatigue and diabetes-related
symptoms. Evidence is conflicting regarding the onset of fatigue among persons
with T1DM and the relationship between fatigue and diabetes duration. The
prevalence of fatigue is likely influenced by disease physiology, psychological
stress, and lifestyle factors, but more research is needed to confirm these
relationships as causal inference is unclear.
PMID- 29944066
TI - [Status and development of the role as Parkinson Nurse in Germany - an online
survey].
AB - : Status and development of the role as Parkinson Nurse in Germany - an online
survey Abstract. BACKGROUND: In Germany there is a course for Parkinson Nurses
(PN) since 2006. Content, structure and organization of their tasks have not yet
been systematically described for Germany. AIM: How is the typical working day of
PN organised in Germany? Which tasks do they have? Which conditions are promoting
or inhibiting for their work? METHODS: Among the graduates of the course, an
online survey was conducted from September to November 2016. 39 questionnaires
were analysed descriptively (response rate 34 %). RESULTS: 52 % of PN work in
specialist hospitals and 26 % work in hospitals of maximum medical care. Only 29
% work according to a concept and only 23 % have a job description. 21 % of
respondents no longer work as PN. Counselling and education, information on
medication management, educational advertising on Parkinson' disease as well as
training of other professionals are at the centre of their work. The activities
usually focus the work in the institution; a trans-sectoral support for people
with Parkinson's disease is rare. CONCLUSIONS: In the future, concepts and job
descriptions should be stored in the institutions, which are oriented towards a
cross-institutional orientation framework. On the basis of a common understanding
of roles it is possible to facilitate networking of the PN as well as the co
operation with other specialists. The curriculum at an academic level leads to
the necessary competencies.
PMID- 29944067
TI - Successfully Managing Diabetes in a Community Setting: Evidence From the YMCA of
Greater Richmond Diabetes Control Program.
AB - Purpose The purpose of this study was to describe how a community-academic
partnership developed and implemented a shared goal of evaluating the impact of a
large community-based diabetes self-management program on diabetes care and
mental health outcomes. Methods Data came from the YMCA of Greater Richmond
Diabetes Control Program (DCP), a 12-week, group-format self-management program
led by lay health coaches. Adults with type 2 diabetes (N = 312) completed
baseline assessments of sociodemographic characteristics, diabetes history, and
mental health. Four outcomes were assessed pre- and post-DCP on 141 participants
who completed the program: hemoglobin A1C (A1C), weight, depressive symptoms
(Patient Health Questionnaire-8), and glucose monitoring. The team worked with a
Community Advisory Board throughout the research process. Results The DCP had
wide geographic reach, including lower-income neighborhoods. The average age of
the participants was 53.9 years, 71.4% were female, and 69% were African
American. During the DCP, A1C declined from 8.4% to 7.6% (P < .001), but weight
was unchanged (229.2 vs 227.9, P < .282). During the DCP, the proportion of
participants with clinically significant depressive symptoms declined from 32.4%
to 15.5% (P < .001), and frequency of glucose monitoring significantly increased.
Conclusions The YMCA of Greater Richmond DCP has wide reach into underserved
populations throughout the metropolitan area. This program is effective at
improving diabetes self-management and mental health. Findings have implications
for supporting academic-community partnerships to address diabetes disparities.
PMID- 29944071
TI - Real-world effectiveness of clozapine for intellectual disability: Results from a
mirror-image and a reverse-mirror-image study.
AB - BACKGROUND:: Comorbid mental illness is common in patients with intellectual
disability. Antipsychotics are widely used for these conditions, but the effect
of clozapine remains largely unknown. AIMS:: We aimed to investigate the
effectiveness of clozapine on naturalistic outcomes in patients with intellectual
disability. METHODS:: By combining the national health registers, we identified
all patients in Denmark with intellectual disability initiating clozapine
treatment during the period 1996-2012. We used a mirror-image model to test
whether initiation of clozapine treatment was associated with reduction in
psychiatric admissions and inpatient days, reduction in the number of individuals
performing intentional self-harm or overdose, and less frequent use of
concomitant psychopharmacological treatment. Similar outcome measures were used
in a reverse mirror-image model to investigate the effects of clozapine
termination. RESULTS:: A total of 405 patients with intellectual disability
redeemed clozapine. After initiation of clozapine the number of psychiatric
admissions were reduced by 0.65 admissions (95% CI: 0.31-1.00) and the inpatient
days were reduced by 67.2 days (95% CI: 51.2-83.3), with a similar decrease for
patients with intellectual disability without psychiatric comorbidity. Clozapine
treatment was not found to reduce the number of individuals with intentional self
harm, incidents of overdose, or the use of concomitant psychotropics. In cases
where clozapine treatment was terminated, the number of psychiatric admissions
increased by 0.57 admissions (95% CI: 0.01-1.12). CONCLUSION:: This nationwide
study, which is the largest to date, suggests that treatment with clozapine is
associated with a reduction in psychiatric admissions and inpatient days in
patients with intellectual disability. Further studies evaluating the effects of
clozapine in patients with intellectual disability are warranted.
PMID- 29944072
TI - Managing the risk of intimacy: accounts of disclosure and responsiveness among
people with HIV and intimate partners of people with HIV.
AB - It is well known that concerns about sexual risk tend to decline among people in
intimate relationships where there is established commitment and trust. In the
context of relationships at increased risk for HIV transmission, interactions
involving disclosure and partner responsiveness are key to maintaining intimacy
and physical safety. This paper explores concepts of risk and sexual intimacy
articulated by a community sample of 30 people living with HIV and their intimate
relationship partners. Data revealed the shifts in intimate relationship dynamics
upon the disclosure of an HIV diagnosis, the importance of intimacy in the
context of managing one or both partners' HIV care and responses to new advances
in HIV prophylaxis. Findings suggest that participants' experiences of self
disclosure and partner responsiveness most often resulted in an increased sense
of protectiveness from and for partners. This suggests that health-promoting
messaging should be adapted to be more relevant to intimate couple communication
and mutual support.
PMID- 29944073
TI - The Privatization of Public Hospitals: Its Impact on Financial Performance.
AB - This study examined the effects of public hospitals' privatization on financial
performance. We used a sample of nonfederal acute care public hospitals from 1997
to 2013, averaging 434 hospitals per year. Privatization was defined as
conversion from public status to either private not-for-profit (NFP) or private
for-profit (FP) status. Financial performance was measured by operating margin
(OM) and total margin (TM). We used hospital level and year fixed effects linear
panel regressions with nonlagged independent and control variables (Model 1),
lagged by 1 year (Model 2), and lagged by 2 years (Model 3). Privatization to FP
was associated with 17% higher OM (Model 2) and 9% higher OM (Model 3), compared
with 3%, 4%, and 6% higher OM for privatization to NFP for all three Models,
respectively. Privatization to FP was associated with 7% higher TM (Model 2) and
privatization to NFP was associated with 2% higher TM (Model 3).
PMID- 29944074
TI - A Comprehensive Psychometric Examination of the Lesbian, Gay, and Bisexual
Knowledge and Attitudes Scale for Heterosexuals (LGB-KASH).
AB - Heterosexual attitudes toward individuals with other sexual orientations and
identities, such as lesbian, gay, bisexual, transgender, intersex, asexual, etc.
(LGBTQIA+), have been conceptualized as multidimensional and wide-ranging. With
the objective of measuring these attitudes, Worthington and colleagues developed
the Lesbian, Gay, and Bisexual Knowledge and Attitudes Scale for Heterosexuals
(LGB-KASH). In this article, 540 college students were administered the LGB-KASH;
these data were examined for their psychometric properties of the instrument
using a sequential approach. The first step included descriptive analysis,
including internal consistency measures and association rules, followed by the
evaluation of dimension structure with factor analysis
(confirmatory/exploratory), and, finally, item analysis using non-parametric
(Mokken scale analysis) and parametric approaches (item response theory).
Specific to the LGB-KASH factor structure, the current structure was not
supported by these data; however, alternative subsets of items that could be used
to revise the original instrument to obtain a more psychometrically sound measure
are suggested.
PMID- 29944075
TI - Intravenous treprostinil via an implantable pump in pediatric pulmonary arterial
hypertension.
AB - Intravenous prostacyclin-based therapy improves survival in children with
pulmonary arterial hypertension (PAH), but is typically administered via an
external infusion pump, which places a considerable burden on the patient.
Implanted pumps may overcome some of the limitations of external pumps. We
describe the first long-term use of an implanted pump for intravenous
treprostinil delivery in a pediatric patient with PAH. Our patient was
experiencing marked dyspnea on exertion despite triple combination therapy with
bosentan, sildenafil, and inhaled iloprost. Parenteral prostacyclin-based therapy
was discussed and the patient rejected options involving external pumps; she
finally chose intravenous treprostinil delivery via an implanted pump (LENUS
Pro(r); fixed flow rate; 20 ml reservoir). The patient underwent pump
implantation in July 2012 (aged 14 years) under general anesthesia with no peri-
or postoperative complications. She showed marked improvements in fatigue and
dyspnea over the subsequent weeks, and her inhaled iloprost regimen was slowly
decreased and stopped after six months. During follow-up, the pump showed an
unexpected, progressive increase in flow rate that allowed a treprostinil dose of
170 ng/kg/min to be achieved, but at the cost of shortened intervals between
refills. The pump was therefore replaced in August 2017 with a newer model with
an adjustable flow rate (Siromedes(r)). A catheter dislocation was corrected
under local anesthesia one week after the replacement surgery. The patient is
currently receiving treprostinil 170 ng/kg/min with percutaneous refills every 12
13 days. Thus, implantable pumps might be a valuable alternative to external
pumps for treprostinil infusion in pediatric PAH.
PMID- 29944076
TI - Reducing Psychological Stress in Peripartum Women With Heart Rate Variability
Biofeedback: A Systematic Review.
AB - Peripartum women are exposed to a variety of stressors that have adverse health
consequences for the maternal-child dyad (e.g., impaired bonding). To combat
these adverse health consequences, heart rate variability biofeedback (HRVBF) may
be implemented by holistic nurses to aid peripartum women experiencing a high
level of stress. A systematic review was completed using the guidelines
established in the PRISMA (Preferred Reporting Items for Systematic Reviews and
Meta-Analyses) statement. To be included in the review, studies had to meet the
following criteria: (a) published scientific articles, (b) studies published in
English, (c) experimental, quasi-experimental, or case reports, (d) use of HRVBF
as the main treatment, (e) use of psychological stress as a dependent variable,
and (f) studies published until December 2017. The major findings of this review
can be described as follows: (a) HRVBF and psychological stress in peripartum
women are related concepts, (b) peripartum women who completed HRVBF report a
reduction in stress compared with participants who did not receive HRVBF, and (c)
there is currently no information on the effectiveness of HRVBF on psychological
stress in the first and early second trimester of pregnancy. Overall, this
systematic review of the literature provides objective evidence that HRVBF may be
a potential beneficial adjuvant treatment for stress management in peripartum
women.
PMID- 29944077
TI - Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative
BOLD MRI with Intraoperative and Histologic Validation.
AB - Purpose To validate ferumoxytol-based quantitative blood oxygenation level
dependent (BOLD) MRI for mapping oxygenation of human infiltrative astrocytomas
by using intraoperative measurement of tissue oxygen tension and histologic
staining. Materials and Methods Fifteen patients with infiltrative astrocytomas
were recruited into this prospective multicenter study between July 2014 and
December 2016. Prior to treatment, participants underwent preoperative
quantitative BOLD MRI with ferumoxytol to generate tissue oxygen saturation
(StO2) maps. Two intratumoral sites were identified, one with low StO2 and one
with high StO2. Neuronavigation was used to locate sites intraoperatively for
insertion of oxygen-sensing probes to measure local tissue oxygen tension (PtO2).
Biopsies from both sites were taken and stained for markers of hypoxia (hypoxia
inducible factor 1alpha, carbonic anhydrase IX) and neoangiogenesis (vascular
endothelial growth factor, endoglin [CD105]). Spearman correlation and
nonparametric sign-rank tests were used to analyze data. Results Ten patients
with median age of 58.5 years (interquartile range, 25 years; four men and six
women) completed the study. Because there is no linear relationship between StO2
and PtO2, the ratios of low to high StO2 versus low to high PtO2 in each patient
were compared and a significant correlation was found (r = 0.73; P = .01).
Pathologic analyses revealed differences between carbonic anhydrase IX (P = .03)
for sites of low StO2 versus high StO2. CD105 displayed a similar trend but was
not significant (P = .09). Conclusion Ferumoxytol-based quantitative blood
oxygenation level-dependent MRI can potentially be used as a noninvasive
surrogate for oxygenation mapping in infiltrative astrocytomas. This technique
can potentially be integrated in treatment planning for aggressive targeting of
hypoxic areas in tumors.
PMID- 29944078
TI - Current Applications and Future Impact of Machine Learning in Radiology.
AB - Recent advances and future perspectives of machine learning techniques offer
promising applications in medical imaging. Machine learning has the potential to
improve different steps of the radiology workflow including order scheduling and
triage, clinical decision support systems, detection and interpretation of
findings, postprocessing and dose estimation, examination quality control, and
radiology reporting. In this article, the authors review examples of current
applications of machine learning and artificial intelligence techniques in
diagnostic radiology. In addition, the future impact and natural extension of
these techniques in radiology practice are discussed.
PMID- 29944079
TI - Multiple Administrations of Gadobutrol in the Pediatric Brain: No Change in T1
Signal at MRI.
AB - Purpose To determine whether multiple doses of gadobutrol increase the T1 signal
intensity in the brains of children. Materials and Methods This retrospective
imaging study evaluated 91 children (median age, 5.4 years; age range, 0-17
years) with brain tumors who underwent five or more MR brain examinations at a
single institution. A subgroup of 46 patients received five or more
administrations of gadobutrol (0.1 mmol/kg) and underwent follow-up MRI. T1
signal intensity in the globus pallidus and dentate nucleus was measured at the
first to sixth unenhanced MR brain examination in these children. Globus pallidus
to-corpus callosum and dentate nucleus-to-corpus callosum signal intensity ratios
were analyzed by linear mixed-effect analysis. Subgroup analysis was performed
for six children who underwent 14 or more administrations of gadobutrol. Results
The globus pallidus-to-corpus callosum ratio increased with patient age (absolute
change, 0.0052 per year; 95% confidence interval: 0.0033, 0.0071; P < .0001).
There was no change in the dentate nucleus-to-corpus callosum ratio with age (P =
.30). Among 46 children who received five or more doses of gadobutrol (median
dose, 11 mL; range, 3.9-31 mL), there was no change in signal intensity ratio of
the globus pallidus (P = .17) or dentate nucleus (P = .44). Among six children
who underwent more than 14 administrations of gadobutrol (median dose, 64 mL;
range, 40-91 mL) there was no change in signal intensity ratio of the globus
pallidus (P = .15) or dentate nucleus (P = .50). Conclusion No increase in T1
weighted signal intensity ratio was observed in the globus pallidus or dentate
nucleus after the administration of at least five doses of gadobutrol. (c) RSNA,
2018 Online supplemental material is available for this article.
PMID- 29944080
TI - Machine Detection of High Breast Density: Worse Outcomes for Our Patients.
PMID- 29944081
TI - In Utero Exposure to Gadolinium-based Contrast Agents.
PMID- 29944082
TI - Guidelines for Biopsy of Thyroid Nodules.
PMID- 29944083
TI - Improving Spatial Resolution at CT: Development, Benefits, and Pitfalls.
PMID- 29944084
TI - 4D Flow Meets CT: Can It Compete with 4D Flow MRI?
PMID- 29944085
TI - Phantom Study of In-Stent Restenosis at High-Spatial-Resolution CT.
AB - Purpose To examine the diagnostic performance of high-spatial-resolution (HSR) CT
with 0.25-mm section thickness for evaluating renal artery in-stent restenosis.
Materials and Methods A 0.05-mm wire phantom and vessel phantoms with renal
stents with in-stent stenotic sections of varying diameters were scanned with
both an HSR CT scanner equipped with 160-section multi-detector rows (0.25-mm
section thickness) and a conventional CT scanner. The wire phantom was used to
analyze modulation transfer function (MTF). With the vessel phantoms, the error
rates were calculated as the absolute difference between the measured diameters
and true diameters divided by the true diameters at the narrowing sections. For
qualitative evaluation, overall image quality and diagnostic accuracy for
evaluating stenosis in three stages were assessed by two radiologists.
Statistical analyses included the paired t test, Wilcoxon signed-rank test, and
McNemar test. Results HSR CT achieved 24.3 line pairs per centimeter +/- 0.5
(standard deviation) and 29.1 line pairs per centimeter +/- 0.4 at 10% and 2%
MTF, respectively; and conventional CT was 12.5 line pairs per centimeter +/- 0.1
and 14.3 line pairs per centimeter +/- 0.1 at 10% and 2% MTF, respectively. The
mean error rate of the measured diameter at HSR CT (8.0% +/- 5.8) was
significantly lower than that at at conventional CT (16.9% +/- 9.3; P < .001).
Image quality at HSR CT was significantly better than that at conventional CT (P
< .001), but HSR CT was not significantly superior to conventional CT in terms of
diagnostic accuracy. Conclusion Compared with conventional CT, high-spatial
resolution CT achieved spatial resolutions of up to 29 line pairs per centimeter
at 2% modulation transfer function and yielded improved measurement accuracy for
the evaluation of in-stent restenosis in a phantom study of renal artery stents.
Published under a CC BY 4.0 license.
PMID- 29944086
TI - Quantification of Liver Fibrosis at T1 and T2 Mapping with Extracellular Volume
Fraction MRI: Preclinical Results.
AB - Purpose To evaluate MRI T1 and T2 mapping with calculation of extracellular
volume (ECV) for diagnosis and grading of liver fibrosis. Materials and Methods
Different grades of fibrosis were induced in 60 male Sprague-Dawley rats by bile
duct ligation (BDL) and carbon-tetrachloride (CCl4) intoxication. Portal pressure
was measured invasively, whereas hepatic fibrosis was quantified by
hydroxyproline content, Sirius red staining, and alpha smooth muscle actin
staining. T1 values, T2 values, and ECV were assessed by using quantitative MRI
mapping techniques. Results T1 values in animals 4 weeks after BDL were greater
than in control animals (718 msec +/- 74 vs 578 msec +/- 33, respectively; P <
.001). T2 values at 4 weeks were also greater in animals that underwent BDL than
in control animals (46 msec +/- 6 vs 29 msec +/- 2, respectively; P < .001).
Similar T1 and T2 findings were observed after CCl4 intoxication. ECV was greater
in animals 4 weeks after BDL compared with control animals (31.3% +/- 1.3 vs
18.2% +/- 3.5, respectively; P < .001), with similar results after CCl4
intoxication. High correlations were found between ECV and hepatic hydroxyproline
content (BDL: r = 0.68, P < .001; CCl4: r = 0.65, P < .001), Sirius red staining
(BDL: r = 0.88, P < .001; CCl4: r = 0.82, P < .001), alpha smooth muscle actin
staining (BDL: r = 0.70, P < .001; CCl4: r = 0.73, P < .001), and portal pressure
(BDL: r = 0.54, P = .003; CCl4: r = 0.39, P = .043). Conclusion Elevation of T1
and T2 values and ECV was associated with severity of liver fibrosis and portal
hypertension in an experimental animal model.
PMID- 29944087
TI - Ex Vivo Mercury Release from Dental Amalgam after 7.0-T and 1.5-T MRI.
AB - Purpose To evaluate ex vivo mercury release from dental amalgam after 7.0-T and
1.5-T MRI. Materials and Methods The authors evaluated 60 caries-free molar or
premolar teeth that had been extracted for clinical indications. Two-sided
cavities were opened in each tooth and amalgam fillings applied. After 9 days,
two groups of 20 randomly selected teeth were placed in 20 mL of artificial
saliva immediately followed by 20 minutes of MRI exposure at 1.5 or 7.0 T. A
control group of teeth was placed in artificial saliva without undergoing MRI
exposure. The teeth were removed from the artificial saliva 24 hours later, and
the saliva was analyzed for mercury content by using inductively coupled plasma
mass spectrometry. One-way analysis of variance was used to compare the mean
mercury values among the three independent groups, and the Tukey test was used
for multiple comparisons of the mean values. Results The mean mercury content of
the artificial saliva was 673 MUg/L +/- 179 in the 7.0-T MRI group, 172 MUg/L +/-
60 in the 1.5-T MRI group, and 141 MUg/L +/- 152 in the control group. The
mercury content in the 7.0-T group was greater than that in both the 1.5-T group
(P < .001; 95% confidence interval: 368 MUg/L, 633 MUg/L) and the control group
(P < .001; 95% confidence interval: 416 MUg/L, 648 MUg/L). There was no
statistically significant difference in mercury content between the 1.5-T and
control groups (P = .84; 95% confidence interval: -164 MUg/L, 110 MUg/L).
Conclusion In an ex vivo setting, mercury was released from amalgam fillings
after exposure to 7.0-T MRI but not 1.5-T MRI.
PMID- 29944088
TI - Automated Volumetric Analysis of Mammographic Density in a Screening Setting:
Worse Outcomes for Women with Dense Breasts.
AB - Purpose To describe screening outcomes from BreastScreen Norway stratified by
volumetric breast density (VBD). Materials and Methods This retrospective study
included data from 107 949 women aged 50-69 years (mean age +/- standard
deviation, 58.7 years +/- 5.6) who underwent 307 015 screening examinations from
2007 to 2015. Automated software classified mammographic density as nondense (VBD
<7.5%) or dense (VBD >=7.5%). Rates and distributions of screening outcomes
(recall, biopsy, screen-detected and interval breast cancer, positive predictive
values of recall and of needle biopsy, sensitivity, specificity, and
histopathologic tumor characteristics) were analyzed and stratified by density.
Tests of proportions, including propensity score and t tests, were used. Results
In 28% (87 021 of 307 015) of the screening examinations, the breasts were
classified as dense. Recall rates for women with nondense versus dense breasts
were 2.7% (5882 of 219 994) and 3.6% (3101 of 87 021); biopsy rates were 1.1%
(2359 of 219 994) and 1.4% (1209 of 87 021); rates of screen-detected cancer were
5.5 (1210 of 219 994) and 6.7 (581 of 87 021) per 1000 examinations; and rates of
interval breast cancer were 1.2 (199 of 165 324) and 2.8 (185 of 66 674) per 1000
examinations, respectively (P < .001 for all). Sensitivity was 82% (884 of 1083)
for nondense breasts and 71% (449 of 634) for dense breasts, whereas specificity
was 98% (160 973 of 164 440) and 97% (64 250 of 66 225), respectively (P < .001
for both). For screen-detected cancers, mean tumor diameter was 15.1 mm and 16.6
mm (P = .01), and lymph node-positive disease was found in 18% (170 of 936) and
24% (98 of 417) (P = .02) of women with nondense and dense breasts, respectively.
Conclusion Screening examinations of women with dense breasts classified by using
automated software resulted in higher recall rate, lower sensitivity, larger
tumor diameter, and more lymph node-positive disease compared with women with
nondense breasts.
PMID- 29944089
TI - Intracardiac Flow at 4D CT: Comparison with 4D Flow MRI.
AB - Purpose To investigate four-dimensional (4D) flow CT for the assessment of
intracardiac blood flow patterns as compared with 4D flow MRI. Materials and
Methods This prospective study acquired coronary CT angiography and 4D flow MRI
data between February and December 2016 in a cohort of 12 participants (age
range, 36-74 years; mean age, 57 years; seven men [age range, 36-74 years; mean
age, 57 years] and five women [age range, 52-73 years; mean age, 64 years]). Flow
simulations based solely on CT-derived cardiac anatomy were assessed together
with 4D flow MRI measurements. Flow patterns, flow rates, stroke volume, kinetic
energy, and flow components were quantified for both techniques and were compared
by using linear regression. Results Cardiac flow patterns obtained by using 4D
flow CT were qualitatively similar to 4D flow MRI measurements, as graded by
three independent observers. The Cohen kappa score was used to assess
intraobserver variability (0.83, 0.79, and 0.70) and a paired Wilcoxon rank-sum
test showed no significant change (P > .05) between gradings. Peak flow rate and
stroke volumes between 4D flow MRI measurements and 4D flow CT measurements had
high correlation (r = 0.98 and r = 0.81, respectively; P < .05 for both).
Integrated kinetic energy quantified at peak systole correlated well (r = 0.95, P
< .05), while kinetic energy levels at early and late filling showed no
correlation. Flow component analysis showed high correlation for the direct and
residual components, respectively (r = 0.93, P < .05 and r = 0.87, P < .05),
while the retained and delayed components showed no correlation. Conclusion Four
dimensional flow CT produced qualitatively and quantitatively similar
intracardiac blood flow patterns compared with the current reference standard,
four-dimensional flow MRI. (c) RSNA, 2018 Online supplemental material is
available for this article.
PMID- 29944090
TI - Prospective Relations between Social Comparison Orientation and Weight Loss
Outcomes.
AB - Maintenance of weight loss after behavioral intervention tends to be poor, and
there is need for an improved understanding of factors that are associated with
successful maintenance. Social comparison is known to be a powerful influence on
treatment outcomes for group-based behavioral weight loss programs, but little is
known about the role of individual differences in social comparison orientation
(i.e., tendency to value comparison information) in this context. The goal of
this study was to examine prospective relations between social comparison
orientation and long-term weight loss outcomes (percent weight loss and aerobic
intensity physical activity) among participants in behavioral weight loss
treatment. Participants (n = 161, MAge = 54, MBMI = 34.4 kg/m2) completed a
measure of social comparison orientation at pre-treatment baseline. Height and
weight were measured in the research center and aerobic-intensity physical
activity was assessed via accelerometer at baseline, mid- and end-of-treatment,
and at 6 and 12 months post-treatment (representing maintenance). Multilevel
models tested prospective relations between comparison orientation and treatment
outcomes over time, with emphasis on differences during the post-treatment
maintenance phase. Stronger (vs. weaker) general comparison orientation was
associated with better maintenance of aerobic-intensity physical activity.
However, stronger (vs. weaker) orientation toward comparisons with better-off
others (i.e., upward comparison) was associated with less weight loss success
during and after treatment. Social comparison orientation thus shows meaningful
relations with long-term maintenance of key outcomes in group-based behavioral
weight loss treatment, and warrants further investigation in this context.
PMID- 29944091
TI - Exploring how workplace and social policies relate to caregivers' financial
strain.
AB - Informal caregiving is a critical component of the US long-term care system, but
can have significant negative impacts on caregiver employment, finances, and well
being. An online survey of Colorado caregivers was piloted in 2016-17 to explore
whether workplace and social policies such as access to paid family leave and
public health insurance can buffer the negative financial impacts of caregiving
and help caregivers to remain in the workforce. Using standardized measures, the
survey assessed caregivers' employment and financial status, well-being (physical
and mental health, caregiver strain, benefits of caregiving), access to workplace
supports, and covariates (e.g., caregiver demographics, health, social support,
and service utilization). Ninety-five caregivers, recruited through community
agency partners, completed the survey. Respondents were predominately female
(89%), middle-aged (M = 57), non-Hispanic White (64%) or Latino/a (22%), and
caring for a parent (40%) or spouse (30%) for over one year. Half (51%) reported
working full- or part-time jobs, while 16.4% had stopped working because of
caregiving. In multivariate regression modeling, predictors of financial strain
included the care recipients' financial strain and the caregiver's reduction or
ceasing of work. Medicare may be protective to minimize caregivers' need to
reduce or cease work. Implications for caregivers' ability to stay engaged in the
workforce and prepare for their own retirement are explored.
PMID- 29944092
TI - Ruegeria denitrificans sp. nov., a marine bacterium in the family
Rhodobacteraceae with the potential ability for cyanophycin synthesis.
AB - Strain CECT 5091T, an aerobic, marine, Gram-reaction- and Gram-stain-negative,
chemoheterotrophic bacterium was isolated from oysters harvested off the Spanish
Mediterranean coast. Analysis of the 16S rRNA gene sequence placed the strain
within the genus Ruegeria, in the family Rhodobacteraceae, with 16S rRNA gene
similarities of 98.7, 98.7 and 98.4 % to Ruegeria conchae, Ruegeria atlanticaand
Ruegeria arenilitoris, respectively. Average nucleotide identities (ANI) and in
silico DNA-DNA hybridization (DDH) were determined, comparing the genome sequence
of CECT 5091T with those of the type strains of 12 species of the genus Ruegeria:
the values obtained were always below the thresholds (95-96 % ANI, 70 % in silico
DDH) used to define genomic species, proving that CECT 5091T represents a novel
species of the genus Ruegeria. The strain was slightly halophilic and mesophilic,
with optimum growth at 26 degrees C, pH 7.0 and 3 % salinity, it required sodium
and magnesium ions for growth and was able to reduce nitrate to dinitrogen.
Carbon sources for growth include some carbohydrates (d-ribose, d-glucose, l
rhamnose, N-acetyl-d-glucosamine) and multiple organic acids and amino acids. The
major cellular fatty acid was summed feature 8 (C18 : 1omega7c and/or C18 :
1omega6c), representing 70 % of the total fatty acids. Carbon monoxide oxidation,
cyanophycin synthetic ability and phosphatidylglycerol, diphosphatidylglycerol
and phosphatidylcholine production are predicted from genome annotation, while
bacteriochlorophyll a production was absent. The DNA G+C content of the genome
was 56.7 mol%. We propose the name Ruegeriadenitrificans sp. nov. and strain CECT
5091T (=5OM10T=LMG 29896T) as the type strain for the novel species.
PMID- 29944093
TI - Sphingomonas tabacisoli sp. nov., a member of the genus Sphingomonas, isolated
from rhizosphere soil of Nicotiana tabacum L.
AB - A Gram-staining-negative, aerobic, motile and rod-shaped bacterium, designated
strain X1-8T, was isolated from rhizosphere soil of Nicotiana tabacum L.
collected from the tobacco produce base located in Kunming, south-west PR China.
Cells showed oxidase-negative and catalase-positive reactions and were motile by
means of peritrichous flagella. Growth occurred at 25-40 degrees C and pH 6.0
8.0 with optimal growth at 30-35 degrees C, pH 7.0. The major respiratory
lipoquinone was Q-10. C16 : 0 and summed feature 8 (C18 : 1omega7c and/or C18 :
1omega6c) were identified as major cellular fatty acids. The profile of polar
lipids contained diphosphatidylglycerol, phosphatidylglycerol,
phosphatidylethanolamine, phosphatidylmethylethanolamine, sphingoglycolipid,
phosphatidylcholine and one unidentified glycolipid. The major polyamine was sym
homospermidine. The genomic DNA G+C content was 66.5 mol%. The results of
phylogenetic analysis based on 16S rRNA gene sequences indicated that X1-8T
should be affiliated to the genus Sphingomonasand formed a clade with most
closely related species Sphingomonas changbaiensisNBRC 104936T. The results of
16S rRNA gene sequences similarity analysis indicated that X1-8T had the highest
similarity with S. changbaiensisNBRC 104936T (98.4 %) and lower than 96.0 % with
other species of the genus Sphingomonas. DNA-DNA hybridization data indicated
that X1-8T represented a novel genomic species of the genus Sphingomonas. The
characteristics determined in the polyphasic taxonomic study indicated that X1-8T
represents a novel species of the genus Sphingomonas, for which the name
Sphingomonas tabacisoli sp. nov. (type strain X1-8T=KCTC 62032T=CGMCC 1.16275T)
is proposed.
PMID- 29944095
TI - Nanoparticles Targeting and Remodeling Tumor Microenvironment for Cancer
Theranostics.
AB - The tumor microenvironment (TME) is featured with aberrant vasculatures, specific
physiological parameters, viscoelastic extracellular matrix and stromal cells,
which are important factors in tumor initiation, development and metastasis. The
components in TME form physical/biological barriers for drug delivery and
therapy, and also contribute to resistance to treatment and immunosuppression.
The advances in nanobiotechnology have offered a myriad of nanoparticles for
targeting and treating tumors through the passive or active targeting strategies.
However, the barriers in TME always limit the drug delivery and therapeutic
efficacy of nanoparticles. To cope with this, recent strategies have employed
nanoparticles to target and remodel tumor microenvironment, while a variety of
nanoparticles have been developed with different functions for this score. In
this review, we have described the typical features of tumor microenvironment
along with their roles in tumor progression, and then focused on recent
progresses in development and application of nanoparticles to target and remodel
TME for enhanced cancer therapy.
PMID- 29944094
TI - Streptomyces geranii sp. nov., a novel endophytic actinobacterium isolated from
root of Geranium carolinianum L.
AB - A novel endophytic actinomycete, designated A301T, was isolated from the root of
Geranium carolinianum Linn collected from Mount Emei in China and characterized
using a polyphasic approach. Growth occurred at 10-37 degrees C, pH 6-11 and in
the presence of 0-5 % NaCl (w/v). Strain A301T contained ll-diaminopimelic acid
as the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell
hydrolysates included galactose and ribose. The predominant menaquinones were MK
9(H6) and MK-9(H8). The major cellular fatty acids were C15 : 0, C16 : 0,
anteiso-C15 : 0 and iso-C16 : 0. The polar lipid profile consisted of
diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, two
unidentified phospholipids, three unidentified lipids and two unidentified
aminophospholipids. Strain A301T shared the highest 16S rRNA gene sequence
similarity to Streptomyces cinereorubersubsp. fructofermentans NBRC 15396T (98.1
%) and Streptomyces turgidiscabies ATCC 700248T (98.1 %). The DNA-DNA relatedness
values between strain A301T and the two above-mentioned members of the genus
Streptomyces were 42.6 % and 47.2 %, respectively. The G+C content of the DNA was
70.5 mol%. On the basis of the polyphasic approach and DNA-DNA hybridization
data, strain A301T represents a novel species within the genus Streptomyces, for
which the name Streptomyces geranii sp. nov. is proposed. The type strain is
A301T (=CGMCC 4.7422T=JCM 32177T).
PMID- 29944096
TI - Targeting Delivery of Rapamycin with Anti-Collagen IV Peptide Conjugated
Fe3O4@Nanogels System for Vascular Restenosis Therapy.
AB - Coronary arterial disease (CAD) remains the leading cause of death globally.
Although percutaneous coronary interventions (PCI) are most of the important
clinical procedure for CAD treating, unfortunately, vascular restenosis is proved
as the major drawback of PCI. Because of the complex nature of the restenotic
process, the efficacy of drug administration is emphasized. Targeting drug
delivery systems become a promising experimental approach for restenosis therapy.
Hence, we design and fabricate a thermo/pH-responsive nanogel system with the
magnetic inner core as the multifunctional nanocarrier for drug delivery and
MRI/fluorescence imaging. To this end, NIPAm-based Fe3O4 core-shell structure
nanogel is synthesized as the responsive nanosystem for rapamycin (RAPA)
delivery, and the surface conjugation with anti-collagen IV peptide makes the
nanosystem an ideal candidate for targeting delivery of RAPA. Based on its
stimuliresponsive properties, the nanosystem shows desirable intracellular
release behavior of RAPA and significantly reduces the adverse effect of RAPA.
The in vitro cytotoxicity evaluations present the biosafety profiles and
antiproliferation performance of the drug-loaded nanogels. Meanwhile, the
magnetic Fe3O4 inner core shows enhanced T2 weight sensitivity, providing a high
potential for imaging-guiding therapy. In the balloon angioplasty model,
targeting nanogels are demonstrated accumulation at the injured site of artery.
Compared with the non-targeting nanogels, treatment with peptide conjugated
nanogels attenuates neointimal hyperplasia more effectively. The biochemical
assays further reveal that the enhanced restenosis prevention effect is
contributed to the selective release of RAPA at the injured sites of artery,
which notably potentiate the nanosystem as a systemically targeting delivered
treatment.
PMID- 29944097
TI - Biodegradable Interlayer-Crosslinked Polymer Micelles with Reduction Sensitivity
for Non-Small Cell Lung Cancer Therapy.
AB - To achieve higher therapeutic efficiency with catabatic side effects, desirable
nanocarriers should be designed to retain the loaded drug tightly during the
systemic circulation, but release the drug rapidly and efficiently upon
endocytosis by tumor cells. Herein, we synthesized a novel folate conjugated
poly(ethylene glycol)-poly(L-glutamic acid)-poly(L-phenylalanine) (folate-PEG
PLG(HS)-PPhe) copolymer to achieve a desired controlled delivery of doxorubicin
(DOX). The copolymer could self-assemble into interlayer-crosslinked micelles
with reduction sensitivity, and DOX was successfully loaded into the interior of
copolymer. The interlayer-crosslinked disulfide bond at the intermediate region
of between PEG and poly(L-phenylalanine) led to significant improvement of the
system stability through the introduction of an additional mechanism of
carrier/carrier interaction. The crosslinked interlayer could be cleaved at the
desired target site under tumor-relevant reductive conditions and DOX were
rapidly released from the DOX loaded folate-PEG-PLG (HS)-PPhe micelles (DOX
fPGPM), and significantly lowered the drug leakage without glutathione (GSH).
Importantly, the DOX-fPGPM exhibited significantly higher antitumor efficiency
both in vitro and in vivo in comparison with free DOX, and Doxil (commercial
doxorubicin-loaded liposomes). Biodistribution studies showed that DOX more
effectively accumulated in tumor tissue after iv injection of DOXfPGPM. The DOX
fPGPM designed in this work potentially resolved the dilemma between systemic
stability and rapid intracellular drug release, and would provide a promising
nanomedicine platform for cancer therapy.
PMID- 29944098
TI - Delivery of a Modified mRNA Encoding IL-22 Binding Protein (IL-22BP) for Colon
Cancer Gene Therapy.
AB - As an alternative form of genetic material, mRNA lacks a CpG island and can
function without crossing the nuclear membrane. These properties make mRNA less
of a potential immune stimulant than plasmid DNA. Therefore, chemically modified
mRNA is an effective alternative to plasmid DNA for gene therapy. In this study,
cationic liposomes were used as a vector to transport mRNA complexes that had
been compressed using protamine and to obtain high mRNA transport and expression
efficiency. The liposome-protamine-IL-22BP mRNA complex can strongly inhibit the
growth of C26 tumour cells by inducing apoptosis, inhibiting tumour angiogenesis
and increasing the number of immune cells that infiltrate the tumour
microenvironment. The obvious tumour regression and safety of this approach were
observed in peritoneal metastasis and subcutaneous xenograft models. The
antitumour effect of the liposome protamine mRNA complex was as good as that for
a plasmid DNA complex, and demonstrated the potential for mRNA-based gene
therapy.
PMID- 29944099
TI - A Novel Delivery System of Cyclovirobuxine D for Brain Targeting: Angiopep
Conjugated Polysorbate 80-Coated Liposomes via Intranasal Administration.
AB - The blood-brain barrier (BBB) poses a challenge for the treatment of
cerebrovascular diseases including cerebral ischemia-reperfusion injury,
Parkinson's syndrome, and cerebral tumors. Nanotechnology has developed as a
promising strategy for drug delivery applications to the brain, especially
liposomes (Lps) that have shown an intrinsic ability to cross the BBB. Angiopep-2
(ANG), a ligand for low-density lipoprotein receptor-related protein-1 (LRP1), is
a good prospect for use as a targeting ligand for brain delivery using Lps. It
was also reported that Polysorbate 80 (Tween 80, T80) plays a special role in
brain targeting. Moreover, the nasal drug delivery method has attracted increased
attention with its brain targeting capability in the clinical treatment of
cerebrovascular diseases. The aim of this work was to evaluate the capability of
Angiopep-conjugated Polysorbate 80-Coated Liposomes in the delivery of
cyclovirobuxine D across the BBB in vitro and in vivo. For this purpose, we first
synthesized DSPE-PEG2000-Angiopep-2 then cyclovirobuxine D was encapsulated in
Angiopep-conjugated Polysorbate 80-Coated Liposomes (T80-An2-CVB-D-Lps) prepared
by thin film evaporation and an ultrasonic technique. Formulations were
characterized in terms of encapsulation efficiency, transmission electron
microscope (TEM) morphology, size distribution, and zeta potential. Angiopep
conjugated Polysorbate 80-Coated Liposomes enhanced in vitro BBB transport of CVB
D compared to the nontargeted liposomes and the CVB-D solution in the BBB model
consisting of brain microvascular endothelial (bEnd.3) cells. To evaluate the
brain targeting of T80-An2-CVB-D-Lps in vivo, microdialysis samples were
collected from the striatum and blood simultaneously. Rats were dosed with brain
targeting liposomes, CVB-D liposomes and CVB-D solution by intranasal
administration and with brain-targeting liposomes by intravenous injection. The
results showed that T80-An2-CVB-D-Lps were spherical, small (approximately 80
nm), homogeneously dispersed, negatively charged and possessed a high
encapsulation efficiency. T80-An2-CVB-D-Lps crossed the BBB model better than the
other treatments did. In addition, in a pharmacodynamic study, there was a higher
AUC in the brain after T80-An2-CVB-D-Lps by intranasal administration. In
conclusion, T80-An2-Lps can enhance the BBB permeability and improve the
transport of CVB-D to the brain. This coadministration strategy can be utilized
to enhance the brain accumulation in other cerebrovascular diseases.
PMID- 29944100
TI - Tea Polyphenols Functionalized and Reduced Graphene Oxide-ZnO Composites for
Selective Pb2+ Removal and Enhanced Antibacterial Activity.
AB - New materials with good purification of water quality (heavy metal ions removal
and inhibition of bacteria) have increasingly attracted more research attentions.
Considering the advantages of zinc oxide (ZnO) and tea polyphenol functionalized
and reduced graphene oxide (TPG), the TPG-ZnO composites were prepared under
moderate hydrothermal method and characterized by various methods. Lead ions
(Pb2+) and Streptococcus mutans (S. mutans) were used to evaluate the adsorption
capacity and antimicrobial activity of the TPG-ZnO, respectively. The influencing
factors for heavy metal ions removal (pH, contact time), adsorption kinetics, and
isotherms were discussed in this article. Furthermore, their antibacterial
properties against S. mutans were investigated by counting of colony-forming
units (CFU), scanning electron microscope (SEM) and confocal laser scanning
microscopy (CLSM). Results showed that the novel TPG-ZnO composites presented
higher adsorption efficiency for Pb2+ (98.92%) compared with pure ZnO and
enhanced antibacterial activity effects (99.99%) towards S. mutans, compared with
pure ZnO and TPG (P < 0.05). The TPG-ZnO composites are therefore promising water
purification materials for application in high-efficient removal of heavy metal
ions and inhibition of bacterial growth.
PMID- 29944101
TI - In Vivo Dopamine Biosensor Based on Copper(I) Sulfide Functionalized Reduced
Graphene Oxide Decorated Microelectrodes.
AB - A novel dopamine biosensor based on carbon fiber microelectrodes (CFMEs) modified
with copper(I) sulfide functionalized nanocomposites of the reduced graphene
oxide (Cu2S/RGO) has been explored for the sensitive detection of dopamine and in
vivo monitoring the neurotransmitters released by Drosophila's brain. The as
prepared Cu2S/RGO decorated microelectrodes were characterized by scanning
electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), and cyclic
voltammetry (CV). Our observations demonstrate that Cu2S/RGO-CFMEs exhibited
excellent catalytic activity and high selectivity for dopamine with relatively
low detection limit (24 nM), wide linear range (i.e., from 0.1-20 MUM) and
outstanding reproducibility. Furthermore, the as-prepared new dopamine biosensor
with high sensitivity and good stability was readily used to detect the amount of
dopamine in the brain of drosophila, indicating the potential and promising
application in the in vivo measurement of neurotransmitters without other
electrochemical interference such as histidine, ascorbic acid, uric acid, and
others.
PMID- 29944102
TI - Echogenic Chitosan Nanodroplets for Spatiotemporally Controlled Gene Delivery.
AB - To attain attractive ultrasound-responsive gene delivery, a new kind of echogenic
chitosan nanodroplets (CND) was developed to explore the potential to deliver
genes in a spatiotemporally controlled manner. Self-assembled amphiphilic
chitosan micelles of nanoscale size were fabricated to encapsulate hydrophobic
perfluoropentane into the inner cores. The resulting CND presented a positive
surface charge, enabling the formation of nano-complexes with genetic cargo
through electrostatic interactions. Agarose-gel electrophoresis further confirmed
the ability of CND to bind DNA. CND was also observed to protect DNA from
degradation by nucleases. A temperature-dependent droplet-to-bubble conversion
was also demonstrated. More importantly, our study revealed that CND in
combination with ultrasound could significantly enhance gene delivery. In
conclusion, our study demonstrated a novel carrier with great potential for
efficient ultrasound-mediated gene delivery to specific tissues in a
spatiotemporally controlled manner.
PMID- 29944103
TI - Targeting Detection and Inhibition of Methicillin-Resistant Staphylococcus aureus
Pneumonia with a Theranostic Mesoporous Silica-Based Platform.
AB - In this study, non-invasive early stage diagnosis of methicillin-resistant
Staphylococcus aureus-related pneumonia and related anti-inflammatory profiles
with theranostic platforms were reported. Mesoporous silica NPs were first
synthesized and chemically modified to bear an amino group and further covalently
bind to amino-2,4,6-triiodoisophthalic acid and anti-methicillin-resistant S.
aureus antibodies. The drug-loaded NPs were characterized by transmission
electron microscopy, dynamic light scattering analysis and X-ray photoelectron
spectra. MTT and broth dilution assays were used to investigate the
biocompatibility and antibacterial potency of the platform. In vivo computed
tomography analysis was performed in rats infected with different kinds of
pneumonia, and anti-inflammatory studies such as bronchoalveolar lavage and
pathological assays were used to test the capability of our nanomedicine as a
theranostic platform. In addition, the long-term safety of the hybrid NPs was
investigated via hematological and biochemical assays.
PMID- 29944104
TI - Fluorescence Resonance Energy Transfer Visualization of Molecular Delivery from
Polymeric Micelles.
AB - Polymeric micelles are important carriers for anticancer drug delivery. However,
rare papers focused on the dynamic of drug in the core of micelles. In this
paper, we used fluorescence resonance energy transfer (FRET) technique to
investigate the dynamic diffusion of drug from polymeric micelles. mPEG-PCL
diblock copolymers were used as carriers. A pair of fluorescence molecules Cy3
and Cy5 was selected to evoke the FRET phenomenon. Cy5 was immobilized on the
terminal group of PCL segments, Cy3 was encapsulated in the Cy5 modified
polymeric micelles as the model drug. The drug loaded polymeric micelles were
incubated with 4T1 breast cancer cells. The FRET was observed to explore the
dynamic of Cy3 in the micelles. The results showed that the Cy3 loaded micelles
were stable in aqueous solution as the energy-transfer efficiency (ETE,
I660/I565) rarely decreased even when the time was as long as 120 h. The ETE
increased with the content of encapsulated Cy3. The FRET spectra showed that the
ETE of the Cy3 loaded polymeric micelles lowered with the release of Cy3 in PBS.
The intracellular tracking of the Cy3 loaded micelles found more than 60% loaded
drug was release within 12 h with the calculation of ETE in FRET spectra and it
was same to confocal laser scanning and flow cytometry results.
PMID- 29944105
TI - miR-135a-5p and miR-124-3p Inhibit Malignancy of Glioblastoma by Downregulation
of Syndecan Binding Protein.
AB - Due to its high invasiveness, glioblastoma is difficult to treat by surgery,
radiotherapy, chemotherapy or any combination therapy. Syndecan binding protein
(SDCBP), a widely distributed intracellular scaffold protein, has an important
role in both physiological and pathological process. In the current work, we have
identified target sequences for miR-135a-5p and miR-124-3p in the 3'-untranslated
region of the SDCBP mRNA. Therefore, we have investigated the relationship
between SDCBP, miR-135a-5p and miR-124-3p in glioblastoma multiforme cells T98G
and U87 in vitro and in vivo. Dual luciferase activity assay documented that
SDCBP is, in fact, the target of miR-135a-5p, miR-124-3. Western blot, qRT-PCR,
proliferation, migration, and invasion assays have demonstrated that of silencing
SDCBP or overexpressing miR-135a-5p/miR-124-3p significantly interferes with the
malignant properties of glioblastoma cells. In vivo studies have shown that
silencing SDCBP or overexpressing miR-135a-5p/miR-124-3p result in a marked
decrease of tumor size and prolong life of tumor-bearing mice. A therapy
combining the three treatments inhibits synergistically subcutaneous tumor growth
in nude mice. In conclusion, proliferation, migration and invasion of
glioblastoma can be inhibited by targeted regulation of SDCBP through
upregulation of miR-135a-5p and miR-124-3p.
PMID- 29944106
TI - Silver Nanoparticle Exposure Induces Neurotoxicity in the Rat Hippocampus Without
Increasing the Blood-Brain Barrier Permeability.
AB - Silver nanoparticles (Ag-NPs) can enter the brain and subsequently induce
neurotoxicity. However, the toxicity of Ag-NPs on the blood-brain barrier (BBB)
and the underlying mechanism(s) of action on the hippocampus in vivo are not well
understood. To investigate Ag-NP suspension (Ag-NPS)-induced toxicity on the BBB
and neurons, Sprague-Dawley rats were randomly divided into 3 groups, and Ag-NPS,
Ag-ion, and 5% sucrose solution (vehicle control) were administrated
intravenously, respectively. After 24 h exposure to Ag-NPS, the BBB permeability
was not significantly changed. However, the Ag concentrations in the brain
tissues were only detected in the Ag-NPS group. Gene expression results indicated
that the expression of Claudin 4 (tight junction protein) was significantly
decreased. Furthermore, astrocyte foot swelling, neuron shrinkage and Ag-NP like
particles were observed under transmission electron microscopy. Global gene
expression analysis showed that 502 genes were up-regulated and 703 genes were
down-regulated in the hippocampi treated with Ag-NPS. In the Ag-NPS-treated
group, 78 biological functions were changed based on gene ontology (GO) and 34
signaling pathways were significantly changed using Kyoto Encyclopedia of Genes
and Genomes (KEGG) pathway analysis, which were associated with the neuroactive
ligand-receptor interaction, cytokine-cytokine receptor interaction, calcium
signaling pathway and MAPK signaling pathway. In comparison, 27 GO and 9 KEGG
pathways were changed in the released Ag-ion-treated group. Ag-NPS decreased
C1qtnf3 expression and increased Adra1d expression to affect MAPK signaling
pathway, which promoted inflammation and apoptosis in the hippocampus. Moreover,
Ag-NPS significantly increased Spp1, Cacna1s and Tacr3 mRNAs expression, which
may result in intracellular calcium increasing and initiate cell death.
Furthermore, Ag-NPS affected calcium signaling pathway and neuroactive ligand
receptor (Grin2a, Drd2, and Adra1d), which are crucial in diverse cellular
functions in the brain including cognition and neurodevelopment. These results
draw our attention to the importance of Ag-NP-induced toxicity in the rat
hippocampus and provide a better understanding of its toxicological mechanisms in
vivo.
PMID- 29944107
TI - Nanocochleates as the Potential Delivery Systems for Oral Antitumor of
Hydroxycamptothecin.
AB - It remains a major challenge to improve the oral antitumor efficacy of
hydroxycamptothecin (HCPT). The aim of this study was to develop the oral HCPT
formulation via nanocochleates technology. After HCPT was incorporated into
calcium ions-induced nanocochleates, its oral bioavailability significantly
enhanced, up to a 2.3-fold. Most importantly, in vivo antitumor effect of HCPT
loaded nanocochleates could be achieved upon oral administration to hepatoma
bearing BALB/c-nude mice, showing the remarkable inhibition of tumor growth as
compared to normal saline, HCPT suspensions and HCPT-loaded liposomes. Caco-2
cells, as an in vitro model, were conducted to investigate the absorption
mechanisms of intestinal tract. Caco-2 transport studies indicated that HCPT
loaded nanocochleates were uptake via clathrin- and caveolin-mediated
endocytosis. Furthermore, ZO-1, F-actin and claudin-4, known as three cellular
tight junction proteins, were obvious down-regulation, which suggested that HCPT
loaded nanocochleates could open cellular tight junctions and paracellular route.
In conclusion, nanocochleates served as a promising vehicle to facilitate the
oral delivery of HCPT.
PMID- 29944108
TI - In Vivo Vaginal Fungal Load Reduction After Treatment with Itraconazole-Loaded
Polycaprolactone-Nanoparticles.
AB - Itraconazole (ITZ) has a broad spectrum of action and is commonly used for the
treatment of fungal infections. Topic administration of ITZ is a promising
strategy to improve vulvovaginal candidiasis treatment, which can be further
optimized by its encapsulation in nanoparticles to increase drug delivery and
reduce ITZ toxicity. In this work, we designed polycaprolactone nanoparticles
containing ITZ and evaluated in vivo the efficacy of this yet unexplored
approach. Nanocapsules (ITZ-NC) and nanospheres (ITZ-NS) were obtained by
nanoprecipitation. ITZ-NC presented encapsulation efficiency of 99%, mean
diameter of 190 nm, PDI 0.1 and zeta potential of -15 mV. ITZ-NS showed
encapsulation efficiency of 97%, mean diameter of 120 nm, PDI 0.1 and zeta
potential of -10 mV. Both particles were efficiently freeze-dried using 10%
trehalose + 10% sucrose. Nanoparticles were then incorporated in a viscous
formulation for vaginal application in female Balb/C mice infected with Candida
albicans. Fungal load was significantly reduced in infected animals after
treatment with ITZ-NC but not with ITZ-NS, compared to animals treated with ITZ
solution. Histological analysis showed a clear difference between vaginal tissues
of ITZ-NC and ITZ-NS and ITZ solution-treated animals, which correlated with IL
1beta and TNF-alpha quantification. Animals treated with ITZ-NC showed reduced
cytokine levels and healthy tissue characteristics, while animals treated with
ITZ-NS and ITZ solution showed increased IL-1beta and TNF-alpha levels and
typical tissue inflammation. Our results demonstrate the potential of ITZ-NC to
improve the treatment of vulvovaginal candidiasis after topical application in
the vagina, opening new perspectives for the treatment of this disease.
PMID- 29944109
TI - Olivibacter ginsenosidimutans sp nov., with ginsenoside converting activity
isolated from compost, and reclassification of Pseudosphingobacterium domesticum
as Olivibacter domesticus comb. nov.
AB - A Gram-stain-negative, aerobic and rod-shaped, bacterium designated as strain
BS18T, was isolated from compost and subjected to a polyphasic taxonomic
analysis. On the basis of the results of 16S rRNA gene sequence analysis, BS18T
represents a member of the genus Olivibacter of the family Sphingobacteriaceaeand
is most closely related to Olivibacter oleidegradansTBF2/20.2T (93.7 %),
Olivibacter jilunii 14-2AT (93.6 %), Olivibacter ginsengisoli Gsoil 060T (93.6
%), Pseudosphingobacterium domesticumDC186T (93.0 %) and shared <=93.1 % sequence
similarity with the other members of the genus Olivibacter. BS18T contained MK-7
as the predominant quinone, iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 4
(iso-C15 : 0 2-OH and/or C16 : 1omega7c), as the major fatty acids and
phosphatidylethanolamine (PE) as main polar lipid. BS18T could be distinguished
from the other members of the genus Olivibacter by a number of chemotaxonomic and
phenotypic characteristics. On the basis of the results of polyphasic taxonomic
analysis, BS18T represents a novel species within the genus, for which the name
Olivibacter ginsenosidimutans sp. nov. is proposed. The type strain of
Olivibacter ginsenosidimutans is BS18T (=KACC 16612T=JCM 18200T). It is also
proposed to transfer Pseudosphingobacterium domesticumto the genus Olivibacter,
as Olivibacter domesticus comb. nov. (type strain DC186T=CCUG 54353T=LMG 23837T).
PMID- 29944110
TI - Characterization of neutralizing epitopes in antigenic site B of recently
circulating influenza A(H3N2) viruses.
AB - Influenza A(H3N2) viruses are associated with outbreaks worldwide and can cause
disease with severe complications. The impact can be reduced by vaccination,
which induces neutralizing antibodies that mainly target the haemagglutinin
glycoprotein (HA). In this study we generated neutralizing mouse monoclonal
antibodies (mAbs) against A/Victoria/361/2011 and identified their epitopes by
generating and sequencing escape viruses. The epitopes are located in antigenic
site B, which is near the receptor-binding site and is immunodominant in humans.
Amino acid (aa) substitutions at positions 156, 158, 159, 189, 190 and 193 in
antigenic site B led to reduced ability of mAbs to block receptor-binding. The
majority of A(H3N2) viruses that have been circulating since 2014 are
antigenically distinct from previous A(H3N2) viruses. The neutralization
sensitive epitopes in antigenic site B of currently circulating viruses were
examined with these mAbs. We found that clade 3C.2a viruses, possessing an
additional potential glycosylation site at HA1 position N158, were poorly
recognized by some of the mAbs, but other residues, notably at position 159, also
affected antibody binding. Through a mass spectrometric (MS) analysis of HA, the
glycosylated sites of HA1 were established and we determined that residue 158 of
HA1 was glycosylated and so modified a neutralization-sensitive epitope.
Understanding and monitoring individual epitopes is likely to improve vaccine
strain selection.
PMID- 29944111
TI - Ferrigenium kumadai gen. nov., sp. nov., a microaerophilic iron-oxidizing
bacterium isolated from a paddy field soil.
AB - An iron-oxidizing bacterium, designated strain An22T, which was isolated from a
paddy field soil in Anjo, Japan, was described taxonomically. Strain An22T was
motile by a single polar flagellum, curved-rod, Gram-negative bacterium that was
able to grow at 12-37 degrees C (optimally at 25-30 degrees C) and at pH 5.2
6.8 (pH 5.9-6.1). The strain grew microaerobically and autotrophically by
oxidizing ferrous iron, but did not form stalks, a unique structure of iron
oxides. The major cellular fatty acids were C16 : 0 and C16 : 1omega7c/C16 :
1omega6c. The major respiratory quinones were UQ-10 and UQ-8. The strain
possessed ribulose-1,5-bisphosphate carboxylase/oxygenase indicating an
autotrophic nature via the Calvin-Benson-Bassham cycle. The total DNA G+C content
was 61.4 mol%. 16S rRNA gene sequence analysis revealed that strain An22T was
affiliated with the class Betaproteobacteria and clustered with iron-oxidizing
bacteria, Gallionella ferrugineaJohan (94.8 % similarity) and Ferriphaselus
amnicola OYT1T (94.4 %) in the family Gallionellaceae. Based on the low 16S rRNA
gene sequence similarity to the phylogenetically closest genera and the
combination of unique morphological, physiological and biochemical
characteristics, strain An22T represents a novel genus and species within the
family Gallionellaceae, for which the name Ferrigenium kumadai gen. nov., sp.
nov. is proposed. The type strain is An22T (=JCM 30584T=NBRC 112974T=ATCC TSD
51T).
PMID- 29944112
TI - Streptomyces populi sp. nov., a novel endophytic actinobacterium isolated from
stem of Populus adenopoda Maxim.
AB - A novel endophytic actinobacterium strain, designated A249T, was isolated from
the stem of Populus adenopoda collected at Mount Qingcheng in south-west China.
Its taxonomic position was determined by using a polyphasic approach. The
cultural and morphological characteristics of isolate A249T were consistent with
members of the genus Streptomyces. Growth occurred at 10-37 degrees C, pH 6.0
12.0 and in the presence of 0-4 % (w/v) NaCl. Analysis of the 16S rRNA gene
sequence and phylogenetic trees showed the closest phylogenetic relatives to
strain A249T were Streptomyces shaanxiensis JCM 16925T (98.0 % 16S rRNA gene
sequence similarity) and Streptomyces lanatus JCM 4332T (97.9 %). The DNA-DNA
hybridization values between the strain A249T and the two reference strains
ranged from 41.4 to 49.4 %. The DNA G+C content was 71.7 mol%. The range of
average nucleotide identity values was 81.5-86.7 %. Chemical analysis of cellular
components indicated that strain A249T contained ll-diaminopimelic acid, xylose
and galactose. The predominant menaquinones were MK-9(H6) and MK-9(H8). The polar
lipids were diphosphatidylglycerol, phosphatidylinositol mannosides,
phosphatidylethanolamine, two unidentified lipids, one unidentified phospholipid,
one unidentified aminolipid and one unidentified aminophospholipid. The major
fatty acids comprised C16 : 0, iso-C14 : 0, iso-C15 : 0, iso-C16 : 0, anteiso-C15
: 0 and C16 : 1omega7c. On the basis of the phenotypic and genotypic
differentiation of the three tested strains, isolate A249T is proposed to
represent a novel species of the genus Streptomyces, named Streptomyces populi
sp. nov. The type strain is A249T (=CGMCC 4.7417T=JCM 32175T).
PMID- 29944113
TI - Specific Amino Acids Affect Cardiovascular Diseases and Atherogenesis via
Protection against Macrophage Foam Cell Formation: Review Article.
AB - The strong relationship between cardiovascular diseases (CVD), atherosclerosis,
and endogenous or exogenous lipids has been recognized for decades,
underestimating the contribution of other dietary components, such as amino
acids, to the initiation of the underlying inflammatory disease. Recently,
specific amino acids have been associated with incident cardiovascular disorders,
suggesting their significant role in the pathogenesis of CVD. Special attention
has been paid to the group of branched-chain amino acids (BCAA), leucine,
isoleucine, and valine, since their plasma values are frequently found in high
concentrations in individuals with CVD risk. Nevertheless, dietary BCAA, leucine
in particular, have been associated with improved indicators of atherosclerosis.
Therefore, their potential role in the process of atherogenesis and concomitant
CVD development remains unclear. Macrophages play pivotal roles in the
development of atherosclerosis. They can accumulate high amounts of circulating
lipids, through a process known as macrophage foam cell formation, and initiate
the atherogenesis process. We have recently screened for anti- or pro-atherogenic
amino acids in the macrophage model system. Our study showed that glycine,
cysteine, alanine, leucine, glutamate, and glutamine significantly affected
macrophage atherogenicity mainly through modulation of the cellular triglyceride
metabolism. The anti-atherogenic properties of glycine and leucine, and the pro
atherogenic effects of glutamine, were also confirmed in vivo. Further
investigation is warranted to define the role of these amino acids in
atherosclerosis and CVD, which may serve as a basis for the development of anti
atherogenic nutritional and therapeutic approaches.
PMID- 29944114
TI - Challenging the Cinderella Hypothesis: A New Model for the Role of the Motor Unit
Recruitment Pattern in the Pathogenesis of Myofascial Pain Syndrome in Postural
Muscles.
AB - BACKGROUND: The energy crisis hypothesis, which is a widely accepted model for
the pathogenesis of myofascial pain, has been corroborated by experimental
observations. However, the nature of the insult leading to the energy crisis
remains elusive. A commonly cited model for this insult is the Cinderella
hypothesis, suggesting that hierarchical recruitment of motor units leads to a
disproportional load on small units, thus driving them towards an energy crisis.
New findings cast doubt on this model, showing that in postural muscles motor
units are recruited in rotation, rather than in a hierarchical order, precluding
the formation of the so-called Cinderella units. OBJECTIVE: To explore the
influence of common myofascial predisposing factors such as muscle load and
muscle strength on the relaxation time of postural muscle motor units, assuming
they are recruited in rotation. METHODS: A stochastic model of a postural
skeletal muscle was developed which integrates the energy crisis model and motor
unit rotation patterns observed in postural muscles. Postulating that adequate
relaxation time is essential for the energetic replenishment of motor units, we
explored the influence of different parameters on the relaxation time of
individual motor units under varying conditions of muscle loads and muscle
strengths. RESULTS: The motor unit relaxation/contraction time ratio decreases
with elevated muscle loads and with decreased total muscle strength. CONCLUSIONS:
In a model of a postural muscle, in which motor units are recruited in rotation,
common predisposing factors of myofascial pain, such as increased muscle load and
decreased muscle force, lead to shortened motor unit relaxation periods.
PMID- 29944115
TI - Collaborative study for the establishment of human immunoglobulin BRP replacement
batches.
AB - Human immunoglobulin products are used for the treatment of a number of diseases,
such as primary or secondary immunodeficiencies and autoimmune conditions due to
the complete absence of antibodies or the production of defective
immunoglobulins. Quality control of human immunoglobulin products is essential to
ensure therapeutic functionality and safety. This includes testing for Fc
function and anticomplementary activity (ACA), as well as verification of
appropriate molecular size distribution using size-exclusion chromatography as
prescribed in the European Pharmacopoeia (Ph. Eur.) monographs 0338, 0918, 2788
and 1928. To this end, specific biological reference preparations (BRPs) must be
used. Stocks of these BRPs were running low and therefore a collaborative study
was run by the European Directorate for the Quality of Medicines & HealthCare
(EDQM), under the aegis of the Biological Standardisation Programme, to calibrate
replacement batches. Seventeen laboratories, including manufacturers and Official
Medicines Control Laboratories, took part in the study. Several batches of
candidate BRPs were calibrated against human immunoglobulin (ACA and molecular
size) BRP batch 1 and human immunoglobulin (Fc function and molecular size) BRP
batch 1 to ensure continuity. Based on the study results, the candidate BRPs were
adopted by the Ph. Eur. Commission as Ph. Eur. human immunoglobulin for
anticomplementary activity BRP batch 1 and batch 2, Ph. Eur. human immunoglobulin
for Fc function BRP batch 1 and batch 2 and Ph. Eur. human immunoglobulin
(molecular size) BRP batch 2 and batch 3.
PMID- 29944117
TI - A new twist on peer review.
AB - eLife is conducting a trial in which authors will decide how to respond to the
issues raised during peer review.
PMID- 29944116
TI - Recruitment of two dyneins to an mRNA-dependent Bicaudal D transport complex.
AB - We investigated the role of full-length Drosophila Bicaudal D (BicD) binding
partners in dynein-dynactin activation for mRNA transport on microtubules. Full
length BicD robustly activated dynein-dynactin motility only when both the mRNA
binding protein Egalitarian (Egl) and K10 mRNA cargo were present, and electron
microscopy showed that both Egl and mRNA were needed to disrupt a looped, auto
inhibited BicD conformation. BicD can recruit two dimeric dyneins, resulting in
faster speeds and longer runs than with one dynein. Moving complexes
predominantly contained two Egl molecules and one K10 mRNA. This mRNA-bound
configuration makes Egl bivalent, likely enhancing its avidity for BicD and thus
its ability to disrupt BicD auto-inhibition. Consistent with this idea,
artificially dimerized Egl activates dynein-dynactin-BicD in the absence of mRNA.
The ability of mRNA cargo to orchestrate the activation of the mRNP (messenger
ribonucleotide protein) complex is an elegant way to ensure that only cargo-bound
motors are motile.
PMID- 29944119
TI - Inferences on hydrogen bond networks in water from isopermitive frequency
investigations.
AB - Intermolecular hydrogen bonds play a crucial role in determining the unique
characteristics of liquid water. We present low-frequency (1 Hz-40 MHz)
dielectric spectroscopic investigations on water in the presence and absence of
added solutes at different temperatures from 10 degrees C to 60 degrees C. The
intersection points of temperature dependent permittivity contours at the
vicinity of isopermitive frequency (IPF) in water are recorded and its properties
are presumed to be related to the extent of hydrogen bond networks in water. IPF
is defined as the frequency at which the relative permittivity of water is almost
independent of temperature. The set of intersection points of temperature
dependent permittivity contours at the vicinity of IPF are characterized by the
mean [Formula: see text] and root-mean-square deviation/standard deviation
[Formula: see text] associated with IPF. The tunability of M IPF by the addition
of NaCl and MgCl2 salt emphasizes the strong correlation between the
concentration of ions in water and the M IPF. The [Formula: see text] is surmised
to be related to the orientational correlations of water dipoles as well as to
the intermolecular hydrogen bond networks in water. Further, alterations in
[Formula: see text] is observed with the addition of kosmotropic and chaotropic
solutes into water and are thought to arise due to the restructuring of hydrogen
bond networks in water in presence of added solutes. Notably, the solute induced
reconfiguration of hydrogen bond networks in water or often-discussed structure
making/breaking effects of the added solutes in water can be inferred, albeit
qualitatively, by examining the M IPF and [Formula: see text]. Further, the
Gaussian deconvoluted OH-stretching modes present in the Raman spectra of water
and aqueous solutions of IPA and DMF strongly endorses the structural
rearrangements occurring in water in presence of kosmotropes and chaotropes and
are in line with the results derived from the root-mean-square deviation in IPF.
PMID- 29944118
TI - RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs.
AB - Polarised mRNA transport is a prevalent mechanism for spatial control of protein
synthesis. However, the composition of transported ribonucleoprotein particles
(RNPs) and the regulation of their movement are poorly understood. We have
reconstituted microtubule minus end-directed transport of mRNAs using purified
components. A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein
Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein
motor and its accessory complex dynactin, thus defining a minimal transport
competent RNP. Unexpectedly, the RNA is required for robust activation of dynein
motility. We show that a cis-acting RNA localisation signal promotes the
interaction of Egl with BicD, which licenses the latter protein to recruit dynein
and dynactin. Our data support a model for BicD activation based on RNA-induced
occupancy of two Egl-binding sites on the BicD dimer. Scaffolding of adaptor
protein assemblies by cargoes is an attractive mechanism for regulating
intracellular transport.
PMID- 29944120
TI - Inhibitory effects of extracts from Cinnamomum camphora fallen leaves on algae.
AB - Natural allelochemicals are considered as a source of algaecides. To uncover the
anti-algal activity of Cinnamomum camphora fallen leaves and promote their usage
as algaecides, the composition of their water and methanol extracts was analyzed,
and the inhibitory effects of extracts on the growth of Microcystis aeruginosa
and Chlamydomonas reinhardtii, and chlorophyll (Chl) content and photosynthetic
abilities in C. reinhardtii were investigated. Twenty-five compounds were
detected in the water extracts, mainly including terpenoids, esters, alcohols,
and ketones. Compared to water extracts, there were more compounds and higher
concentration in methanol extracts. Both water and methanol extracts inhibited
the growth of the two algae, and 15 mg.ml-1 methanol extracts killed the algal
cells after 48 h. The levels of Chl a and Chl b, as well as maximum quantum yield
of photosystem II photochemistry (Fv/Fm) in C. reinhardtii cells reduced
gradually with increasing the concentration of extracts, while the maximum
quantum yield of non-photochemical de-excitation (phiDO) increased gradually. At
the same concentration, methanol extracts showed stronger inhibitory effects than
water extracts, due to their higher number of compounds and higher concentration.
Therefore, C. camphora fallen leaves have a potential value as an algaecide.
PMID- 29944121
TI - Optimization of process conditions for preparation of activated carbon from waste
Salix psammophila and its adsorption behavior on fluoroquinolone antibiotics.
AB - Salix psammophila (SP), a solid waste abundantly available, was applied as a
precursor to prepare the activated carbon by chemical activation method using
phosphoric acid (H3PO4). Response surface methodology based on Box-Behnken design
was used to optimize the prepared conditions of activated carbon. The effects of
concentration of H3PO4, activation temperature and activation time on the
adsorption performance (expressed by the adsorption capacity of ciprofloxacin
hydrochloride (CIP) and norfloxacin (NOR)) were investigated. The optimum
conditions were obtained using H3PO4 concentration of 67.83%, activation
temperature of 567.44 degrees C and activation time of 86.61 min. The optimum
activated carbon (SPAC) was characterized with scanning electron microscopy
energy dispersive X-ray spectroscopy (SEM-EDS), Brunauer-Emmett-Teller (BET) and
Fourier transform infrared spectroscopy (FTIR). The adsorption behavior of CIP
and NOR on SPAC was carried out and the mechanisms for the adsorption process
were proposed. The equilibrium data were fitted by the Freundlich and Langmuir
isotherm models, which resulted in 251.9 mg/g and 366.9 mg/g of the maximum
monolayer adsorption for CIP and NOR at 25 degrees C, respectively. The best
fitted kinetic model was pseudo-second-order, implying that chemisorption
dominated in the adsorption process. This study indicated that activated carbon
based on Salix psammophila (SPAC) was an excellent adsorbent for removing
fluoroquinolone antibiotics from aqueous solutions.
PMID- 29944122
TI - Microalgae population dynamics growth with AnMBR effluent: effect of light and
phosphorus concentration.
AB - The aim of this study was to evaluate the effect of light intensity and
phosphorus concentration on biomass growth and nutrient removal in a microalgae
culture and their effect on their competition. The photobioreactor was
continuously fed with the effluent from an anaerobic membrane bioreactor pilot
plant treating real wastewater. Four experimental periods were carried out at
different light intensities (36 and 52 MUmol s-1 m-2) and phosphorus
concentrations (around 6 and 15 mgP L-1). Four green algae - Scenedesmus,
Chlorella, Monoraphidium and Chlamydomonas- and cyanobacterium were detected and
quantified along whole experimental period. Chlorella was the dominant species
when light intensity was at the lower level tested, and was competitively
displaced by a mixed culture of Scenedesmus and Monoraphidium when light was
increased. When phosphorus concentration in the photobioreactor was raised up to
15 mgP L-1, a growth of cyanobacterium became the dominant species in the
culture. The highest nutrient removal efficiency (around 58.4 +/- 15.8% and 96.1
+/- 16.5% of nitrogen and phosphorus, respectively) was achieved at 52 MUmol s-1
m-2 of light intensity and 6.02 mgP L-1 of phosphorus concentration, reaching
about 674 +/- 86 mg L-1 of volatile suspended solids. The results obtained reveal
how the light intensity supplied and the phosphorus concentration available are
relevant operational factors that determine the microalgae species that is able
to predominate in a culture. Moreover, changes in microalgae predominance can be
induced by changes in the growth medium produced by the own predominant species.
PMID- 29944123
TI - Evaluating catchment response to artificial rainfall from four weather generators
for present and future climate.
AB - The technical lifetime of urban water infrastructure has a duration where climate
change has to be considered when alterations to the system are planned. Also,
models for urban water management are reaching a very high complexity level with,
for example, decentralized stormwater control measures being included. These
systems have to be evaluated under as close-to-real conditions as possible. Long
term statistics (LTS) modelling with observational data is the most close-to-real
solution for present climate conditions, but for future climate conditions
artificial rainfall time series from weather generators (WGs) have to be used. In
this study, we ran LTS simulations with four different WG products for both
present and future conditions on two different catchments. For the present
conditions, all WG products result in realistic catchment responses when it comes
to the number of full flowing pipes and the number and volume of combined sewer
overflows (CSOs). For future conditions, the differences in the WGs
representation of the expectations to climate change is evident. Nonetheless, all
future results indicate that the catchments will have to handle more events that
utilize the full capacity of the drainage systems. Generally, WG products are
relevant to use in planning of future changes to sewer systems.
PMID- 29944124
TI - Effect of low concentrations of dissolved oxygen on the activity of denitrifying
methanotrophic bacteria.
AB - Chemical energy can be recovered from municipal wastewater as biogas through
anaerobic treatment. Effluent from direct anaerobic wastewater treatment at low
temperatures, however, still contains ammonium and considerable amounts of
dissolved methane. After nitritation, methane can be used as electron donor for
denitrification by the anaerobic bacterium 'Candidatus Methylomirabilis oxyfera'.
It was shown that in the presence of 0.7% O2, denitrifying methanotrophic
activity slightly increased and returned to its original level after oxygen had
been removed. At 1.1% O2, methane consumption rate increased 118%, nitrite
consumption rate increased 58%. After removal of oxygen, methane consumption rate
fully recovered, and nitrite consumption rate returned to 88%. Therefore, traces
of oxygen that bacteria are likely to be exposed to in wastewater treatment are
not expected to negatively affect the denitrifying methanotrophic process. 2.0%
O2 inhibited denitrifying activity. Nitrite consumption rate decreased 60% and
did not recover after removal of oxygen. No clear effect on methane consumption
was observed. Further studies should evaluate if intermittent addition of oxygen
results in increased growth rates of the slow-growing 'Candidatus
Methylomirabilis oxyfera'.
PMID- 29944125
TI - Adsorption of reactive dyes onto chitosan/montmorillonite intercalated composite:
multi-response optimization, kinetic, isotherm and thermodynamic study.
AB - Chitosan/montmorillonite intercalated composite (CTS/MMT) was used as an
effective adsorbent for removal of reactive dyes, i.e. Reactive Black 5 (RB5),
Reactive Red 136 (RR136), Reactive Yellow 145 (RY145) and Reactive Blue 222
(RB222). Taguchi method attached grey relational analysis was applied to
determine the optimal adsorption conditions, including pH, initial concentration
of dye, temperature, adsorbent dosage and contact time, for achieving
simultaneous maximization of removal percentage and adsorption capacity. The
percentage contribution of each adsorption condition was determined in the
analysis of variance and showed that the most effective parameter in removal of
RB5, RY145 and RB222 is the dye solution pH, whereas the initial concentration
was the determining factor for optimum efficiency for the dye RR136. Under
respective optimal condition, the removal percentages and adsorption capacity of
four reactive dyes onto CTS/MMT were both found in the following order: RR136 >
RY145 > RB5 > RB222. The maximum removal percentages of 78.8 and 49.5%, and the
adsorption capacity of 315.20 and 123.75 mg/g were obtained for RR136 and RB222,
respectively. The adsorption behaviors showed that the adsorption kinetics and
isotherms were in best agreement with Avrami fractionary order model and the Toth
isotherm, respectively.
PMID- 29944126
TI - Modelling the bioenergy potential of municipal wastewater treatment plants.
AB - A municipal wastewater treatment plant accounts for a large portion of the total
energy consumption of a municipality. Besides their high energy demand, the
plants also display a significant bioenergy potential. This is due to the
utilisation of the energy content of digester gas and sewage sludge if there
exist suitable units. To maximise the energy recovery efficiency of wastewater
treatment systems (WWTS), it is important to analyse the amount of digester gas
and sludge produced in different types of plants. Therefore, the present paper
deals with designing a tool to answer the following research questions: Which
bioenergy potentials occur in different plant types? Which mass and energy flows
are related to the specific potentials? Which utilisation processes for the
potentials can lead to a high energy recovery efficiency of WWTS? Preliminary
analyses with the designed tool were focused on estimating the level of electric
and thermal energy self-sufficiency of different plant configuration scenarios
including or excluding digester gas and/or sludge utilisation units. First
results based on the level of self-sufficiency and associated energy and disposal
costs show that a digester gas and sewage sludge utilisation should be considered
when designing future WWTS.
PMID- 29944127
TI - Brewery wastewater treatment using MBR coupled with nanofiltration or
electrodialysis: biomass acclimation and treatment efficiency.
AB - Breweries release significant amounts of wastewater loaded with various organic
and mineral materials. Prior studies of membrane bioreactor (MBR) wastewater
treatment have been conducted with very little interest granted to the conditions
of biomass acclimation. This study displays biomass behavior during brewery
wastewater treatment by an aerobic MBR. In addition, nanofiltration and
electrodialysis have been studied as potential post-treatment to decrease mineral
concentrations and permit further water reuse for agriculture. An anoxic/aerobic
laboratory MBR, associated with a flat sulfonated polyether membrane was used for
synthetic brewery wastewater treatment. Biomass acclimation was performed using a
feeding substrate. Organic concentrations in the MBR influent varied from 700 mg
COD/L to 10,600 mg COD/L (COD: chemical oxygen demand) for 110 days. The results
indicate a good acclimation to effluent with high salts and organic matter loads.
Steady evolution of biomass concentration and activities was achieved after 90
days of operation. A reduction of COD of around 95% was obtained with MBR and up
to 99% with nanofiltration post-treatment for the reconstructed brewery effluent
with an organic loading rate of 7 g COD/L.d and a solid and hydraulic retention
time of 30 days and 36 hours. A good reduction of the salt content was also
recorded primarily with the nanofiltration and electrodialysis processes.
PMID- 29944128
TI - Further contributions to the understanding of nitrogen removal in waste
stabilization ponds.
AB - A set of experiments were conducted in Brazil in a pilot-scale waste
stabilization pond (WSP) system (a four-maturation-pond series) treating an
upflow anaerobic sludge blanket (UASB) reactor effluent. Over a year and a half
the pond series was monitored under two flow rate conditions, hence also
different hydraulic retention times and surface loading rates. On-site and
laboratory trials were carried out to assess: (i) ammonia losses by
volatilization using acrylic capture chambers placed at the surface of the ponds;
(ii) organic nitrogen sedimentation rates using metal buckets placed at the
bottom of the ponds for collecting settled particulate matter; (iii) nitrogen
removal by algal uptake based on the nitrogen content of the suspended
particulate matter in samples from the ponds' water column. In addition,
nitrification and denitrification rates were measured in laboratory-based
experiments using pond water and sediment samples. The pond system achieved high
nitrogen removal (69% total nitrogen and 92% ammonia removal). The average total
nitrogen removal rates varied from 10,098 to 3,849 g N/ha.d in the first and the
last ponds, respectively, with the following fractions associated with the
various removal pathways: (i) 23.5-45.6% sedimentation of organic nitrogen; (ii)
13.1-27.8% algal uptake; (iii) 1.2-3.1% ammonia volatilization; and (iv) 0.15
0.34% nitrification-denitrification.
PMID- 29944129
TI - Performance of an indigenous integrated slurry photocatalytic membrane reactor
(PMR) on the removal of aqueous phenanthrene (PHE).
AB - In this study, a slurry photocatalytic membrane reactor (PMR) was developed and
evaluated for the degradation of aqueous phenanthrene (PHE). During continuous
process with a hydraulic retention time (HRT) of 140 min, the maximum PHE
degradation and total organic carbon (TOC) removal efficiencies were found to be
97% and 79%, respectively. The reuse and recovery potential of TiO2 was studied
with continuous recycling. The major intermediates during photodegradation of PHE
were found to be phenanthrenequinone, phenanthenol and fluorine. This study also
includes an investigation of membrane fouling caused by hydrophilic nano TiO2.
The cake layer observed on the membrane surface was characterized by scanning
electron microscopy (SEM), atomic force microscopy (AFM) and energy dispersive
spectroscopy (EDS). In addition, the effect of operating parameters such as pH
and permeate flux on membrane fouling were also investigated. Low permeate flux
and alkaline conditions reduced membrane fouling.
PMID- 29944130
TI - A comparison of removal performance of volatile organic and sulfurous compounds
between odour abatement systems.
AB - Three types of odour abatement systems in sewer networks in Australia were
studied for 18 months to determine the removals of different compounds. Six
volatile sulfurous compounds and seven volatile organic compounds (VOCs) were
further investigated. All types of odour abatement systems exhibited good removal
of hydrogen sulfide with the biotrickling filters (BTFs) showing the highest
consistent removal. Biofilters outperformed BTFs and activated carbon (AC)
filters in the removal of dimethyl mono-, di- and tri-sulfide species at the low
inlet concentrations typically found. AC filters exhibited little VOC removal
with no compound consistently identified as having a removal greater than 0%.
Biofilters outperformed BTFs in VOC removal, yet both had high removal
variability.
PMID- 29944131
TI - Effect of heating temperature and time on the phosphate adsorption capacity of
thermally modified copper tailings.
AB - In the present study, copper tailings were treated at different temperatures (50
650 degrees C) and for various times (0.5-6 hours) and their phosphate
adsorption capacity was investigated. The results showed that heating temperature
significantly affected adsorption capacity. The highest capacity was observed in
treatments at 310-350 degrees C. Heating time did not influence phosphate
adsorption ability of copper tailings. Scanning electron microscopy, Barrett
Joyner-Halenda (BJH), and Fourier transform infrared spectroscopy (FTIR) were
employed to characterize untreated copper tailings (raw CT) and copper tailings
heated at 340 degrees C (CT340). The results showed that CT340 had a rougher
surface, more and smaller pores, a larger surface area and higher FTIR
transmittance than raw CT. These changes in texture might explain the increased
phosphate adsorption of thermally modified copper tailings. Mathematical modeling
showed that the Langmuir nonlinear model was the best fit to the current data.
The maximum adsorption capacities of raw CT and CT340 were predicted as 2.08 mg/g
and 14.25 mg/g at 298 K, pH 6.0, respectively.
PMID- 29944132
TI - The role of sodium carbonate in PAM coagulation-flocculation for oil acidized
wastewater treatment.
AB - The pH value of oil acidized wastewater is relatively low (pH = 6.1), which
seriously affects the flocculation of polyacrylamide (PAM). NaOH was used to
adjust the pH value, but the maximum was only 7.5. The regulation was limited as
the Ca2+ in aqueous phase up to 1,350 mg L-1 consumed OH-. A novel formulation of
Na2CO3 + PAM was proposed to form CaCO3 floc core to facilitate PAM coagulation.
When the concentration was above 400 mg L-1, the PAM precipitation tended to be
maximum, followed by NaOH adjustment of pH to 8.0 that could enhance PAM
flocculation successively. The sewage sludge (SS) remained and residue oil
reduced to 25 mg L-1 and 34mg L-1 respectively. The analysis of the species and
composition of fatty acids indicated that the coagulation-flocculation
selectively effected the sedimentation of saturated fatty acids (SAT). This
provides a new idea for recovery of high value-added residual oil. The optimal
additive of Na2CO3 is expected as promising coagulant aid to improve the PAM
coagulation-flocculation of oil acidized wastewater.
PMID- 29944133
TI - Effect of steam explosion on physicochemical properties of waste activated sludge
and the performance of anaerobic digestion.
AB - The effect of steam explosion on physicochemical properties of sludge and the
performance of anaerobic digestion (AD) was investigated. The steam explosion was
conducted under different combinations of temperature and time, ranging 151-198
degrees C and 4-12 min respectively. The capillary suction time (CST) and
viscosity of the sludge was increased with particle size decreased by improved
hydrolysis temperature and prolonged hydrolysis time. The best sludge
solubilization achieved was 41.3% under pretreatment condition of 198 degrees C
and 4 min. Biogas production was enhanced with the improved sludge
solubilization, and a linear correlation was found between biogas production and
the severity factor (logR0) of steam explosion. However, the biogas productivity
was reduced when the logR0 was increased from 3.79 to 3.96, probably owing to the
generation of refractory organics during the high severity pretreatment. The
temperature of 198 degrees C and the time of 8 min were the recommended
operation parameters of steam explosion pretreatment for sludge AD, which could
improve biogas production by 99.7 mL/g VSfed. The pH and NH4+-N during sludge AD
was increased by steam explosion pretreatment; however, no inhibition on biogas
production was observed.
PMID- 29944134
TI - Kinetic, isotherm, and thermodynamic studies of the adsorption of dyes from
aqueous solution by cellulose-based adsorbents.
AB - In this study, a highly efficient and eco-friendly porous cellulose-based aerogel
was synthesized by grafting polyethyleneimine onto quaternized cellulose (PQC) to
remove the anionic dye Congo Red (CR). The prepared aerogel had a good
flexibility and formability. The adsorbents were characterized by scanning
electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and
elemental analysis. The results showed that there were many amino groups on
CE/PQC aerogel and the structure was porous, which increased the adsorption
capacity. The effects of initial concentration, adsorbent dose, contact time,
temperature, and pH on the dye sorption were all investigated. The adsorption
mechanism was also explored, including adsorption kinetics, adsorption isotherms
and thermodynamic studies of adsorption. The results showed that the adsorption
kinetics and isotherms fitted the pseudo-second-order kinetic model and Langmuir
isotherm, respectively. The Langmuir isotherm revealed that the maximum
theoretical adsorption capacity of the aerogels for CR was 518.403 mg g-1. The
thermodynamic parameters including Gibbs free energy change (DeltaG0), enthalpy
change (DeltaH0) and entropy change (DeltaS0), showed the adsorption process was
exothermic and spontaneous. These results imply that this new absorbent can be
universally and effectively used for the removal of dyes from industrial textile
wastewater.
PMID- 29944135
TI - Filamentous bacteria in the nitrifying activated sludge.
AB - Filamentous bacteria in addition to wastewater treatment are responsible for the
shape of flocs and sedimentation properties of activated sludge. Their dynamics
in activated sludge influences the performance of the whole sewage treatment
plant. Therefore the composition of activated sludge biocenosis and its dynamics
in the nitrification process were investigated. Four laboratory-scale activated
sludge membrane bioreactors fed with wastewater highly concentrated with ammonium
(synthetic wastewater imitating landfill leachate) were operated to obtain a high
rate of nitrification. The sludge age was 8, 12, 24 and 32 days. An additional
fifth reactor was conventionally ammonium loaded at 12-day sludge age and served
as the reference. A shift in filamentous bacteria population was observed in all
operated reactors. There was no influence of sludge age on composition or
abundance of filamentous biocenosis. In high ammonium loaded activated sludge
Nostocoida limicola, Haliscomenobacter hydrossis and also Type 021N were the most
abundant filamentous bacteria. In the reference reactor Type 021N and
Sphaerotilus natans dominated the activated sludge.
PMID- 29944136
TI - Synthesis of magnetic alginate beads based on magnesium ferrite (MgFe2O4)
nanoparticles for removal of Sr (II) from aqueous solution: kinetic, equilibrium
and thermodynamic studies.
AB - Novel magnetic alginate beads (MagAlgbeads) have been developed by incorporation
of magnesium ferrite (MgFe2O4) in alginate beads with the aim of using them in
the removal of strontium from aqueous solution. MagAlgbeads were characterized by
transmission electron microscopy, scanning electron microscopy, X-ray
fluorescence and Fourier transform infrared spectroscopy. The adsorption of
strontium onto MagAlgbeads were found to depend on pH and strontium removal
increases with increasing pH until pH is 6. Strontium adsorption kinetics run
through pseudo-second-order model. Thermodynamically, strontium adsorption was
endothermic and spontaneous. Langmuir isotherm gave good fitting for strontium
removal with adsorption capacity of 505.5 mg/g. These results proved that the
prepared MagAlgbeads are very efficient material for strontium adsorption.
PMID- 29944137
TI - Advanced nitrogen removal from municipal wastewater treatment plant secondary
effluent using a deep bed denitrification filter.
AB - With the improvement of wastewater discharge standards, wastewater treatment
plants (WWTPs) are continually undergoing technological improvements to meet the
evolving standards. In this study, a quartz sand deep bed denitrification filter
(DBDF) was used to purify WWTP secondary effluent, utilizing high nitrate
nitrogen concentrations and a low C/N ratio. Results show that more than 90% of
nitrate nitrogen (NO3-N) and 75% of chemical oxygen demand (COD) could be removed
by the 20th day of filtration. When the filter layer depth was set to 1,600 mm
and the additional carbon source CH3OH was maintained at 30 mg L-1 COD (20 mg L-1
methanol), the total nitrogen (TN) and COD concentrations of DBDF effluent were
stabilized below 5 and 30 mg L-1, respectively. Analysis of fluorescence revealed
that DBDF had a stronger effect on the removal of dissolved organic matter (DOM),
especially of aromatic protein-like substances. High throughput sequencing and
qPCR results indicate a distinctly stratified microbial distribution for the main
functional species in DBDF, with quartz sand providing a good environment for
microbes. The phyla Proteobacteria, Bacteroidetes, and Chloroflexi were found to
be the dominant species in DBDF.
PMID- 29944138
TI - Influence of combined sulfachloropyridazine sodium and zinc on enzyme activities
and biogas production during anaerobic digestion of swine manure.
AB - In order to study the influence of different concentrations of zinc and
sulfachloropyridazine sodium (SCPS) on anaerobic digestion (AD) during biogas
production, we determined the levels of urease, dehydrogenase activity, and
volatile fatty acids (VFAs) in batch tests. The experiments were conducted in
small AD devices at a temperature of 37 degrees C using swine manure and wheat
straw as raw materials. Four digestion trials were performed using different zinc
and SCPS contents: control digestion with no additives (CK), SCPS at 630 mg kg-1
dry weight (S), SCPS at 630 mg kg-1 with zinc at 500 mg kg-1 dry weight (SL), and
SCPS at 630 mg kg-1 with zinc at 5,000 mg kg-1 dry weight (SH). The biogas
accumulation under S was 1.7 times that with CK, while SL and SH produced 78% and
35% of that under S, respectively. Correlation analysis showed that the
accumulated biogas was significantly negatively correlated (p < 0.05) with VFAs,
and the urease activity was significantly negatively correlated (p < 0.01) with
zinc and significantly positively correlated with VFAs (p < 0.05). The
dehydrogenase activity was strongly correlated (p < 0.01) with the biogas
accumulated during the AD of swine manure.
PMID- 29944139
TI - The application of ceramsite ecological floating bed in aquaculture: its effects
on water quality, phytoplankton, bacteria and fish production.
AB - In recent years, biological floating bed technology has been applied increasingly
in aquaculture ponds. In this study we developed a novel floating bed made from
ceramsite and studied its effect on water quality, phytoplankton, bacteria and
fish growth. Water quality was effectively regulated and controlled in ceramsite
floating bed (CFB) ponds with an average transparency of 23.18 cm, ammonia
nitrogen (NH4+-N) of 2.30 mg L-1, total nitrogen (TN) of 5.09 mg L-1 and total
phosphate (TP) of 1.32 mg L-1 which are lower than in control ponds without CFB.
Increased phytoplankton species diversity, bacterial number, metabolic activity
and microbial diversity was observed with CFB. At the end of growth stage, feed
conversion ratio (FCR) was reduced with a total fish yield of 14,838 kg ha-1 at a
survival rate of 77.2% in CFB ponds, which is significantly higher than control
(P < 0.05). These results emphasize the potential of ecological floating bed to
improve water quality, microalgal diversity, reduce the risk of harmful algal
blooms and increase the number, activity and diversity of microorganisms as well
as fish yield.
PMID- 29944141
TI - Movement velocity as a measure of level of effort during resistance exercise.
AB - This study analyzed whether the loss of repetition velocity during a resistance
exercise set was a reliable indicator of the number of repetitions left in
reserve. Following the assessment of one-repetition (1RM) strength and full load
velocity relationship, thirty men were divided into three groups according to
their 1RM strength/body mass: novice, well-trained and highly-trained. On two
separate occasions and in random order, subjects performed tests of maximal
number of repetitions to failure against loads of 65%, 75% and 85% 1RM in four
exercises: bench press, full squat, prone bench pull and shoulder press. For each
exercise, and regardless of the load being used, the absolute velocities
associated to stopping a set before failure, leaving a certain number of
repetitions (2, 4, 6 or 8) in reserve, were very similar and showed a high
reliability (CV 4.4-8.0%). No significant differences in these stopping
velocities were observed for any resistance training exercise analyzed between
the novice, well-trained and highly-trained groups. These results indicate that
by monitoring repetition velocity one can estimate with high accuracy the
proximity of muscle failure and, therefore, to more objectively quantify the
level of effort and fatigue being incurred during resistance training. This
method emerges as a substantial improvement over the use of perceived exertion to
gauge the number of repetitions left in reserve.
PMID- 29944140
TI - TET2 controls chemoresistant slow-cycling cancer cell survival and tumor
recurrence.
AB - Dormant or slow-cycling tumor cells can form a residual chemoresistant reservoir
responsible for relapse in patients, years after curative surgery and adjuvant
therapy. We have adapted the pulse-chase expression of H2BeGFP for labeling and
isolating slow-cycling cancer cells (SCCCs). SCCCs showed cancer initiation
potential and enhanced chemoresistance. Cells at this slow-cycling status
presented a distinctive nongenetic and cell-autonomous gene expression profile
shared across different tumor types. We identified TET2 epigenetic enzyme as a
key factor controlling SCCC numbers, survival, and tumor recurrence. 5
Hydroxymethylcytosine (5hmC), generated by TET2 enzymatic activity, labeled the
SCCC genome in carcinomas and was a predictive biomarker of relapse and survival
in cancer patients. We have shown the enhanced chemoresistance of SCCCs and
revealed 5hmC as a biomarker for their clinical identification and TET2 as a
potential drug target for SCCC elimination that could extend patients' survival.
PMID- 29944142
TI - Transcriptional profiling of stellate ganglia from normotensive and spontaneously
hypertensive rat strains.
AB - The course of hypertension remains poorly understood, although impairment of the
sympathetic nervous systems is thought to play a role in its aetiology. In this
study, RNA-sequencing (RNAseq) was used to identify transcriptomal differences in
the sympathetic stellate ganglia between 16-week-old normotensive Wistar rats and
spontaneously hypertensive rats (SHR). Sequencing quality was assessed by FastQC
and quasi-mapping rate by Salmon. Differential expression results were confirmed
by real time reverse transcriptase Quantitative Polymerase Chain Reaction (qRT
PCR). RNAseq analysis was found to be predictive and representative of
transcriptomal changes when compared to qRT-PCR by correlation analysis. Whether
these changes underpin physiological sympathetic phenotypes associated with
hypertension remains to be established, however this dataset identifies lead
transcripts as a priori targets for further investigation.
PMID- 29944143
TI - High content screen for identifying small-molecule LC3B-localization modulators
in a renal cancer cell line.
AB - Forms of selective autophagy have now been recognized to regulate flux in many
intracellular processes. Specific pathways and functions have been identified for
mitophagy, ERphagy, and other selective autophagies; yet there is no consensus in
whether and how autophagy regulates protein maintenance in and around the
nucleus. Such processes are of interest for potential degradation of DNA and
nuclear envelope proteins in various disease states. The mechanistic details of
such nucleus-related autophagic processes remain elusive due to the lack of
chemical or genetic regulators to manipulate and follow the process in vitro.
Here, we describe a high content screen from which we identified small chemical
compounds that can modulate the localization of the autophagy marker MAP1LC3B
(LC3) in renal carcinoma cells. We also describe a pipeline designed for the
execution and analysis of high content screens. The chemical tools discerned from
this screen will allow for the deeper exploration of the mechanism, regulation,
and molecular targets of nuclear-localized LC3 in perturbed cellular states.
PMID- 29944144
TI - Emotional ratings and skin conductance response to visual, auditory and haptic
stimuli.
AB - The human emotional reactions to stimuli delivered by different sensory
modalities is a topic of interest for many disciplines, from Human-Computer
Interaction to cognitive sciences. Different databases of stimuli eliciting
emotional reaction are available, tested on a high number of participants.
Interestingly, stimuli within one database are always of the same type. In other
words, to date, no data was obtained and compared from distinct types of emotion
eliciting stimuli from the same participant. This makes it difficult to use
different databases within the same experiment, limiting the complexity of
experiments investigating emotional reactions. Moreover, whereas the stimuli and
the participants' rating to the stimuli are available, physiological reactions of
participants to the emotional stimuli are often recorded but not shared. Here, we
test stimuli delivered either through a visual, auditory, or haptic modality in a
within participant experimental design. We provide the results of our study in
the form of a MATLAB structure including basic demographics on the participants,
the participant's self-assessment of his/her emotional state, and his/her
physiological reactions (i.e., skin conductance).
PMID- 29944145
TI - A design framework and exemplar metrics for FAIRness.
PMID- 29944146
TI - Time-lapse imagery and volunteer classifications from the Zooniverse Penguin
Watch project.
AB - Automated time-lapse cameras can facilitate reliable and consistent monitoring of
wild animal populations. In this report, data from 73,802 images taken by 15
different Penguin Watch cameras are presented, capturing the dynamics of penguin
(Spheniscidae; Pygoscelis spp.) breeding colonies across the Antarctic Peninsula,
South Shetland Islands and South Georgia (03/2012 to 01/2014). Citizen science
provides a means by which large and otherwise intractable photographic data sets
can be processed, and here we describe the methodology associated with the
Zooniverse project Penguin Watch, and provide validation of the method. We
present anonymised volunteer classifications for the 73,802 images, alongside the
associated metadata (including date/time and temperature information). In
addition to the benefits for ecological monitoring, such as easy detection of
animal attendance patterns, this type of annotated time-lapse imagery can be
employed as a training tool for machine learning algorithms to automate data
extraction, and we encourage the use of this data set for computer vision
development.
PMID- 29944147
TI - Response to Letter to the Editor: "Endocrine Disorders in Primary Mitochondrial
Disease".
PMID- 29944148
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1177/2055207615605644.].
PMID- 29944149
TI - Molecular motions in a fluxional (eta6-indenyl)tricarbonylchromium hemichelate: a
density functional theory molecular dynamics study.
AB - A comprehensive Density Functional Theory (DFT) study is reported on molecular
motions occurring in a hemichelate complex, formally composed of the (eta3-2
methylallyl)Pd(ii) cation bonded to a (eta6-indenyl)tricarbonylchromium anion,
that has been recognized as being highly fluxional in a previous experimental
study (C. Werle, M. Hamdaoui, C. Bailly, X.-F. Le Goff, L. Brelot and J.-P.
Djukic, J. Am. Chem. Soc., 2013, 135, 1715-1718). Its dynamics can be decomposed
into three molecular motions: (i) the indenyl ligand can switch from a eta1 to a
eta3 binding mode to Pd, (ii) the Cr(CO)3 moiety forms loose interactions with
Pd, and can potentially rotate around the aryl-Cr axis, and (iii) the binding
mode of the 2-methylallyl ligand to Pd may undergo partial decoordination or
rotation around the Pd-C axis. Herein, DFT based molecular dynamics simulations
have been performed to provide microscopic insights into the dynamical behaviour
of the complex on a 100 ps timescale. QTAIM analyses have been performed over
trajectories to investigate the rearrangement of its electronic structure over
time. Next, free energy calculations, following the metadynamics approach, have
been undertaken to compute thermodynamic and kinetic data relative to the
molecular rearrangements occurring in the complex. The results show that the
fastest motion is the ring slippage of the indenyl ligand, and that this motion
is coupled with the rotation of the 2-methylallyl ligand. Conversely, the Cr(CO)3
rotation is significantly slower, however, a fast rocking motion is observed,
consisting of transient approaches of carbonyl ligands to Pd. QTAIM analyses
point to loose Pd/carbonyl and Pd/Cr interactions on average, that significantly
evolve over time as fluxional motions occur.
PMID- 29944150
TI - The proportion of Met80-sulfoxide dictates peroxidase activity of human
cytochrome c.
AB - The peroxidase activity of cytochrome c is proposed to contribute to apoptosis by
peroxidation of cardiolipin in the mitochondrial inner membrane. However,
cytochrome c heme is hexa-coordinate with a methionine (Met80) on the distal
side, stopping it from acting as an efficient peroxidase. The first naturally
occurring variant of cytochrome c discovered, G41S, has higher peroxidase
activity than wild-type. To understand the basis for this increase and gain
insight into the peroxidase activity of wild-type, we have studied wild-type,
G41S and the unnatural variant G41T. Through a combined kinetic and mass
spectrometric analysis, we have shown that hydrogen peroxide specifically
oxidizes Met80 to the sulfoxide. In the absence of substrate this can be further
oxidized to the sulfone, leading to a decrease in peroxidase activity. Peroxidase
activity can be correlated with the proportion of sulfoxide present and if fully
in that form, all variants have the same activity without a lag phase caused by
activation of the protein.
PMID- 29944152
TI - A robust split-luciferase-based cell fusion screening for discovering myogenesis
promoting molecules.
AB - Myogenesis-promoting chemicals are an important source of new pharmaceuticals for
the treatment of skeletal muscle atrophy that impairs quality of life. This
report presents a robust and quantitative bioluminescence-based assay for
screening myogenesis-promoting compounds in chemical libraries. The assay system
consists of two stable C2C12 myoblast cell lines, each of which expresses either
an N-terminal or a C-terminal split luciferase fragment fused to a naturally
split DnaE intein as an indicator for cell fusion. Cell fusion during myogenesis
induces bioluminescence in the cytosol because of the reconstitution of
luciferases. The luminescence intensity quantitatively represents the progress in
the cell fusion and therefore indicates the extent of myogenesis. We applied this
assay system to a high-throughput screening of myogenesis-promoting compouns in
1191 pharmacologically proven bioactive small molecules, which revealed two
chemical compounds as myogenesis-promoting compounds: Imatinib and Doxazosin
mesylate. The assay system enabled a robust and quantitative evaluation of the
extent of myogenesis through simple luminescence measurements, and is expected to
be widely applicable for high-throughput screening of cell fusion-promoting and
inhibiting molecules.
PMID- 29944151
TI - Effect of ionic strength on shear-thinning nanoclay-polymer composite hydrogels.
AB - Nanoclay-polymer shear-thinning composites are designed for a broad range of
biomedical applications, including tissue engineering, drug delivery, and
additive biomanufacturing. Despite the advances in clay-polymer injectable
nanocomposites, colloidal properties of layered silicates are not fully
considered in evaluating the in vitro performance of shear-thinning biomaterials
(STBs). Here, as a model system, we investigate the effect of ions on the
rheological properties and injectability of nanoclay-gelatin hydrogels to
understand their behavior when prepared in physiological media. In particular, we
study the effect of sodium chloride (NaCl) and calcium chloride (CaCl2), common
salts in phosphate buffered saline (PBS) and cell culture media (e.g., Dulbecco's
Modified Eagle's Medium, DMEM), on the structural organization of nanoclay
(LAPONITE(r) XLG-XR, a hydrous lithium magnesium sodium silicate)-polymer
composites, responsible for the shear-thinning properties and injectability of
STBs. We show that the formation of nanoclay-polymer aggregates due to the ion
induced shrinkage of the diffuse double layer and eventually the liquid-solid
phase separation decrease the resistance of STB against elastic deformation,
decreasing the yield stress. Accordingly, the stress corresponding to the onset
of structural breakdown (yield zone) is regulated by the ion type and
concentration. These results are independent of the STB composition and can
directly be translated into the physiological conditions. The exfoliated nanoclay
undergoes visually undetectable aggregation upon mixing with gelatin in
physiological media, resulting in heterogeneous hydrogels that phase separate
under stress. This work provides fundamental insights into nanoclay-polymer
interactions in physiological environments, paving the way for designing clay
based injectable biomaterials.
PMID- 29944153
TI - Formation of arrays of planar, murine, intestinal crypts possessing a
stem/proliferative cell compartment and differentiated cell zone.
AB - A simple, in vitro intestinal model recapitulating key aspects of crypt
architecture and physiology would facilitate our understanding the impact of
drugs, foods and microbial metabolites on the intestine. To address the
limitations of previously reported intestinal in vitro platforms, we developed a
planar crypt array that replicated the spatial segregation and physiologic
responses of primary mouse intestinal epithelial cells in the large intestine.
Collagen was coated across an impermeable film possessing an array of microholes
creating two regions of distinct stiffness and porosity (above and outside the
microholes). Primary mouse colon epithelial cells formed a continuous monolayer
across the array with a proliferative cell zone above the microholes and a
nonproliferative or differentiated cell region distant from the microholes.
Formation of a chemical gradient of growth factors across the array yielded a
more complete or in vivo-like cell segregation of proliferative and
differentiated cells with cell migration outward from the proliferative cell zone
into the differentiated zone to replace apoptotic dying cells much as occurs in
vivo. Short chain fatty acids (microbial metabolites) applied to the luminal
surface of the crypt array significantly impacted the proliferation and
differentiation of the cells replicating the known in vivo effects of these fatty
acids. Importantly this planar crypt array was readily fabricated and maintained,
easily imaged with properties quantified by microscopy, and compatible with
reagent addition to either the luminal or basal fluid reservoirs. The ability to
observe simultaneously stem/proliferative and differentiated cell behavior and
movement between these two compartments in response to drugs, toxins,
inflammatory mediators or microbial metabolites will be of widespread utility.
PMID- 29944154
TI - Effects of Low-Protein Diet on lipid and anthropometric profiles of patients with
chronic kidney disease on conservative management.
AB - INTRODUCTION: Chronic Kidney disease (CKD) patients have a high prevalence of
cardiovascular mortality, and among the risk factors are dyslipidemia and
obesity, common findings in the early stages of CKD. The aim of this study was to
evaluate the effects of low protein diet (LPD) on the lipid and anthropometric
profile in non-dialysis CKD patients. METHODS: Forty CKD patients were studied
(20 men, 62.7 +/- 15.2 years, glomerular filtration rate (GFR) 26.16 +/- 9.4
mL/min/1.73m2). LPD (0.6g/kg/d) was prescribed for six months and, biochemical
and anthropometric parameters like body mass index (BMI), waist circumference and
body fat mass (assessed by dual X-ray absorptiometry - DXA) were evaluated before
and after six months with LPD. RESULTS: After six months of nutritional
intervention, patients presented reduction on BMI (from 28.1 +/- 5.6 to 27.0 +/-
5.3 Kg/m2, p = 0.001), total cholesterol (from 199.7 +/- 57.1 to 176.0 +/-
43.6mg/dL, p = 0.0001), LDL (from 116.2 +/- 48.1 to 97.4 +/- 39.1 mg/dL, p =
0,001) and uric acid (from 6.8 +/- 1.4 to 6.2 +/- 1.3 mg/dL, p = 0.004). In
addition, GFR values were increased from 26.2 +/- 9.5 to 28.9 +/- 12.7mL/min (p =
0.02). The energy, proteins, cholesterol and fiber intake were reduced
significantly. CONCLUSION: LPD prescribe to non-dialysis CKD patients for six
months was able to improve some cardiovascular risk factors as overweight and
plasma lipid profile, suggesting that LPD can be also an important tool for
protection against cardiovascular diseases in these patients.
PMID- 29944155
TI - Understanding the causes of mortality post-transplantation - there is more than
meets the eye.
PMID- 29944156
TI - High Flow and volume overload: The saga continues.
PMID- 29944157
TI - Solitary functioning kidney in children: clinical implications.
AB - INTRODUCTION: Children with solitary functioning kidney (SFK) are prone to
develop long term problems, which are not well represented in the literature. The
extent to which the presence of associated congenital anomalies of kidney and
urinary tract (CAKUT) further de-stabilize renal function is to be addressed.
OBJECTIVE: This study was conducted to evaluate the etiology, presentation,
presence of CAKUT, and renal damage in children with SFK. METHODS: All children
with SFK who presented to the department of pediatric surgery from March 2014 to
May 2016 were included in the study. Children with malignancy were excluded from
the study. RESULTS: Of the 20 patients with SFK, 14 (70%) had primary SFK (8 with
agenesis and 6 with multicystic dysplastic kidney), 6 (30%) belonged to secondary
SFK group, among them 3 had pelviureteric junction obstruction, 2 had posterior
urethral valves and 1 had vesicoureteric reflux. Eight (40%) had associated
CAKUT, 4 (20%) were asymptomatic while 8 (40%) had UTI and 6 (30%) had
hypertension. Ten (50%) patients had reduced glomerular filtration rate (GFR)
suggesting compromised renal function. CONCLUSION: Children with SFK have high
morbidity especially when associated with ipsilateral CAKUT. Long-term periodical
follow up is essential in these patients to improve clinical outcome.
PMID- 29944158
TI - The importance of histopathology in the diagnosis of isolated renal sarcoidosis:
a case report.
AB - INTRODUCTION: Sarcoidosis is a systemic inflammatory disease of unknown etiology,
characterized by the presence of non-caseating granulomas in several organs;
renal impairment alone is a rare condition. When it affects the kidneys, the most
prevalent manifestations are hypercalcemia and hypercalciuria. This paper aims to
address the topic of renal sarcoidosis, by means of a case report, and reinstate
the importance of histopathology in its diagnosis. METHODS: The data came from an
observational clinical study with a qualitative approach, through an interview
with the renal sarcoidosis patient and data from her medical records. CASE
REPORT: Patient D.M.S., 50 years old, Caucasian, presented with reddish eyes and
body pains lasting for fifteen days as first manifestations of the disease. Upon
kidney ultrasound scan, we found renal parenchymal nephropathy. Serial renal
function and metabolic tests reported anemia and progressive urea and creatinine
changes, as well as hypercalcemia and hypercalciuria, confirming acute kidney
failure (AKF). A histopathological examination suggested the diagnosis, which was
confirmed by clinical, laboratory and histopathological data. There was
therapeutic resolution after steroid therapy. DISCUSSION: The symptomatology of
sarcoidosis is diverse and often non-specific. Renal manifestation, which usually
occurs after organ involvement, is present in less than 5% of patients, and about
1% to 2% of these patients may develop AKF. CONCLUSIONS: The use of
histopathology together with clinical and laboratory data to diagnose isolated
renal sarcoidosis, rule out other etiologies and introduce early treatment is of
paramount importance.
PMID- 29944159
TI - Inappropriate activity of local renin-angiotensin-aldosterone system during high
salt intake: impact on the cardio-renal axis.
AB - Although there is a general agreement on the recommendation for reduced salt
intake as a public health issue, the mechanism by which high salt intake triggers
pathological effects on the cardio-renal axis is not completely understood.
Emerging evidence indicates that the renin-angiotensin-aldosterone system (RAAS)
is the main target of high Na+ intake. An inappropriate activation of tissue RAAS
may lead to hypertension and organ damage. We reviewed the impact of high salt
intake on the RAAS on the cardio-renal axis highlighting the molecular pathways
that leads to injury effects. We also provide an assessment of recent
observational studies related to the consequences of non-osmotically active Na+
accumulation, breaking the paradigm that high salt intake necessarily increases
plasma Na+ concentration promoting water retention.
PMID- 29944160
TI - Tubulointerstitial nephritis and uveitis syndrome in children: report of three
cases.
AB - Tubulointerstitial nephritis and uveitis syndrome is a rare and probably
underdiagnosed condition. Renal and ocular manifestations may not occur
simultaneously, making the diagnosis more difficult. Nephritis may be
asymptomatic; therefore, renal function evaluation is essential for diagnosis.
Urinary beta2-microglobulin levels may be particularly useful. Uveitis, mostly
anterior, nongranulomatous and bilateral, occurs usually after the onset of
nephritis. Treatment includes corticosteroids and, eventually, other
immunosuppressant agents. Renal disease is usually benign and resolves
spontaneously or after treatment with systemic corticosteroids. Uveitis, however,
may be chronic or recurrent. The authors described the cases of three pediatric
patients diagnosed with tubulointerstitial nephritis and uveitis syndrome. The
goal of this paper was to warn the medical community over the need to screen
patients with uveitis for renal disease.
PMID- 29944161
TI - Initial surgical results of 500 Parathyroidectomies for Hyperparathyroidism
related to chronic kidney disease - mineral and bone disorder.
AB - INTRODUCTION: Surgical treatment of hyperparathyroidism related to chronic kidney
disease is a challenging procedure even for experienced parathyroid surgeons.
Over the years, adjuvant techniques have been developed to assist the medical
team to improve surgical outcomes. However, medical staff in poor countries have
less access to these techniques and the effectiveness of surgery in this context
is unclear. OBJECTIVE: verify the effectiveness of surgery for treatment of
hyperparathyroidism related to chronic kidney disease without adjuvant
techniques. METHODS: Over a 5-years period, patients with hyperparathyroidism
that had clinical therapeutic failure were evaluated for surgical treatment.
Total parathyroidectomy with autograft or subtotal resection were the selected
procedures. Surgeries were performed in a tertiary hospital in Brazil without the
assistance of some of the adjuvant techniques that are usually applied, such as
frozen section, nerve monitoring, and gamma probe. Intraoperative PTH and
localization pre-operative exams were applied, but with huge restrictions.
RESULTS: A total of 518 patients with hyperparathyroidism (128 secondary and 390
tertiary) were surgically treated. Total parathyroidectomy were performed in
81.5%, subtotal in 12.4%, and 61% of patients had a surgical failure. Of all
failures, only 1.4% needed a second surgery totaling 98.6% of successful initial
surgical treatment. Neck hematoma and unilateral focal fold paralysis occurred in
1.9% and 1.5%, respectively. CONCLUSION: parathyroidectomy is a safe and
reproducible surgical procedure even in the absence of adjuvant techniques.
PMID- 29944162
TI - In vitro effect of uremic serum on barrier function and inflammation in human
colonocytes.
AB - INTRODUCTION: In chronic kidney disease (CKD), it has been suggested that
alterations within the gut are associated with an inflammatory state and uremic
toxicity. Studies suggest that uremia may impair the function of the intestinal
barrier via the promotion of increased intestinal permeability. To understand the
mechanisms that are involved in intestinal barrier damage in the setting of
uremia, we evaluated the in vitro effect of uremic serum on transepithelial
electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial
cells (T84). METHODS: Pools of serum from healthy individuals, patients not on
dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84
cells were incubated for 24 h in medium, of which 10% consisted of the pooled
serum from each group. After incubation, the TER was measured and the following
parameters were determined by flow cytometry: expression of toll-like receptors
(TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of
IL-6 in the culture supernatant was determined by ELISA. RESULTS: No difference
was observed among the groups with respect to TER, apoptosis, and ROS or the
expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in
cells that were incubated with pre- and post-HD serum. CONCLUSION: The results
that were obtained from this model suggest that uremic serum per se does not seem
to impair the integrity of intestinal epithelial cells. The increased IL-6
secretion by cells that were incubated with HD serum suggests a potential effect
of uremia in the intestinal inflammatory response.
PMID- 29944163
TI - Polymorphism related to cardiovascular risk in hemodialysis subjects: a
systematic review.
AB - Cardiovascular disease (CVD) is one of the leading causes of mortality in
hemodialysis (HD) subjects. In addition to the traditional risk factors that are
common in these individuals, genetic factors are also involved, with emphasis on
single nucleotide polymorphs (SNPs). In this context, the present study aims to
systematically review the studies that investigated the polymorphisms associated
with cardiovascular risk in this population. In general, the SNPs present in HD
individuals are those of genes related to inflammation, oxidative stress and
vascular calcification, also able of interfering in the cardiovascular risk of
this population. In addition, polymorphisms in genes related to recognized risk
factors for CVD, such as dyslipidemia, arterial hypertension and left ventricular
hypertrophy, also influence cardiovascular morbidity and mortality.
PMID- 29944164
TI - Sub-optimal Application of a High SPF Sunscreen Prevents Epidermal DNA Damage in
Vivo.
AB - The cyclobutane pyrimidine dimer (CPD) is a potentially mutagenic DNA photolesion
that is the basis of most skin cancers. There are no data on DNA protection by
sunscreens under typical conditions of use. The study aim was to determine such
protection, in phototypes I/II, with representative sunscreen-user application. A
very high SPF formulation was applied at 0.75, 1.3 and 2.0 mg/cm2. Unprotected
control skin was exposed to 4 standard erythema doses (SED) of solar simulated
UVR, and sunscreen-treated sites to 30 SED. Holiday behaviour was also simulated
by UVR exposure for 5 consecutive days. Control skin received 1 SED daily, and
sunscreen-treated sites received 15 (all 3 application thicknesses) or 30 (2.0
mg/cm2) SED daily. CPD were assessed by quantitative HPLC-tandem mass
spectrometry (HPLC-MS/MS) and semi-quantitative immunostaining. In comparison
with unprotected control sites, sunscreen significantly (p <= 0.001-0.05) reduced
DNA damage at 1.3 and 2.0 mg/cm2 in all cases. However, reduction with typical
sunscreen use (0.75 mg/cm2) was non-significant, with the exception of HPLC-MS/MS
data for the 5-day study (p <0.001). Overall, these results support sunscreen use
as a strategy to reduce skin cancer, and demonstrate that public health messages
must stress better sunscreen application to get maximal benefit.
PMID- 29944165
TI - Application of participation in clinical practice: Key issues.
AB - BACKGROUND: Rehabilitation services are increasingly targeting involvement in
daily life. In the International Classification of Functioning, Disability and
Health this is referred to as "participation". How-ever, questions have arisen
regarding the conceptualization of participation, and consensus is lacking.
METHODS: The first phase of this study is a critical review of the literature to
detect recurring conceptual problems in the application of participation and how
researchers deal with these. The second phase is a systematic review to identify
how participation measures are operationalized. RESULTS: The critical review
found possible solutions to 4 recurring key limitations: (i) how to deal with
ambiguity and vagueness regarding the term "participation"; (ii) how to
differentiate between activity and participation; (iii) what is the current
empirical knowledge about the subjective aspects of participation; (iv) what are
the different ways to measure participation. The systematic review found 18
instruments operationalizing participation in different ways: (i) unidimensional:
frequency of performing activities; (ii) unidimensional: limitations in
experiencing participation when performing activities; (iii) multidimensional:
multiple subjective dimensions when performing activities; and (iv)
multidimensional: objective and subjective dimensions. DISCUSSION AND CONCLUSION:
Notwithstanding an increasing body of knowledge, some issues remain unclear and
how participation is measured is subject to debate. This results in difficulties
in the use of participation in clinical practice. However, insight into the
current body of knowledge and awareness of shortcomings might help clinicians who
aim to apply participation in practice.
PMID- 29944166
TI - Disfiguring Leukoderma Caused by Banned Cosmetics: A Quiz.
PMID- 29944167
TI - Influence of functional electrical stimulation of the hamstrings on knee
kinematics in stroke survivors walking with stiff knee gait.
AB - OBJECTIVE: To explore whether functional electrical stimulation of the hamstrings
results in improved knee kinematics in chronic stroke survivors walking with a
stiff knee gait. DESIGN: Quasi-experimental. SUBJECTS: Sixteen adult chronic
stroke survivors. METHODS: Survivors received functional electrical stimulation
of the hamstrings, 3 times a week for 1 h during a period of 5 weeks. 3D
kinematics was calculated before the training period and after 5 weeks of
training. Knee kinematics of walking without stimulation before the training
period was compared with walking with stimulation after 5 weeks of training.
(intervention effect). In addition, knee kinematics of walking without
stimulation before the training period was compared with walking without
stimulation after the training period (therapeutic effect). RESULTS: The
intervention effect showed a significant increase, of mean 8.7 degrees (standard
deviation (SD) 8.3, p = 0.001), in peak knee flexion. The therapeutic effect
showed a significant increase in peak knee flexion, of mean 3.1 degrees (SD 4.7,
p = 0.021) Conclusion: The results of this exploratory study suggest an increase
in knee kinematics in swing after functional electrical stimulation of the
hamstrings in stroke survivors walking with a stiff knee gait. The largest
improvement in peak knee flexion in swing was seen when participants walked with
hamstring stimulation. Participants with low neurological impairment responded
better to hamstring stimulation, and there are indications that the effect of
hamstring stimulation can be predicted during a single session. The effect of
functional electrical stimulation is comparable to that of more invasive
treatment options, such as botulinum toxin or soft-tissue surgery. This makes
functional electrical stimulation a feasible treatment option for daily clinical
practice.
PMID- 29944169
TI - Methotrexate for the Treatment of Recalcitrant Primary Localized Cutaneous
Amyloidosis: A Case Series.
PMID- 29944168
TI - Development and validation of a clinically applicable arm use monitor for people
after stroke.
AB - OBJECTIVE: To develop and validate a clinically applicable and easy-to-use
accelerometry-based device to measure arm use in people after stroke; the Activ8
arm use monitor (Activ8-AUM). DESIGN: Development and validation study. PATIENTS:
A total of 25 people at different stages of rehabilitation after stroke were
included in this study. METHODS: The Activ8-AUM consists of 3 single-sensor
Activ8s: one on the unaffected thigh and one on each wrist. Arm use was
calculated by combining movement intensity of the arms with data from body
posture and movements on the leg sensor. Data were divided into 2 sets: one for
determining situation-specific movement intensity thresholds for arm use, and the
other to validate the Activ8-AUM using video recordings. RESULTS: Overall
agreement between the Activ8-AUM and video recordings was 75%, sensitivity was
73% and specificity was 77%. Agreement between the different categories of arm
use ranged from 42% to 93% for the affected arm and from 24% to 82% for the
unaffected arm. CONCLUSION: By combining the movement intensity threshold with
body posture and movements, good agreement was reached between the Activ8-AUM and
video recordings. This result, together with the easy-to-use configuration, makes
the Activ8-AUM a promising device to measure arm use in people after stroke.
PMID- 29944170
TI - Premature Aging Syndrome, Penttinen Type: Report of a Chinese Case with a PDGFRB
Mutation.
PMID- 29944171
TI - The role of Interdisciplinary Teams in Physical and Rehabilitation Medicine.
AB - The increasing complexity of healthcare provision and medical interventions
requires collaboration between large numbers of health professionals. The nature
of the interactions between team members determines whether the pattern of
working is described as multi-, inter- or trans-disciplinary. Such team-working
is an important part of the specialty of Physical and Rehabilitation Medicine.
Grounded in group behaviour theory, team-working demonstrates that joint aims,
trust and willingness to share knowledge, can improve patient outcomes, including
mortality. The synthesis of individual skills and knowledge and working to common
patient goals, has shown benefit in many conditions. This evidence base is
perhaps best in stroke, but has been demonstrated in many other conditions,
including acquired brain injury, back pain, mental health, cardiopulmonary
conditions, chronic pain and hip fracture. There are also considerable benefits
to staff and health organizations in terms of outcome and staff morale. This
review paper examines the evidence for the benefit of such team-working and for
the recommendations of team-working in rehabilitation services.
PMID- 29944172
TI - A Case of Pityriasis Rubra Pilaris Treated Successfully with the
Phosphodiesterase-4 Inhibitor Apremilast.
PMID- 29944173
TI - Renalase is associated with adverse left atrial remodelling and disease burden in
patients with atrial fibrillation undergoing pulmonary vein isolation.
AB - BACKGROUND: Renalase is a catecholamine-metabolising enzyme, but its possible
association with atrial fibrillation (AF) remains unknown. AIM: We sought to
evaluate plasma renalase concentration in patients with AF undergoing pulmonary
vein isolation (PVI) with respect to AF clinical characteristics, left atrial
(LA) remodelling, and PVI efficacy. METHODS: This case-control study included 69
patients (median age 58 years) with either paroxysmal (89%) or persistent (11%)
AF, referred for PVI, and a control group consisting of 15 patients without AF,
matched for age, sex, and comorbidi-ties. An evaluation of transthoracic
echocardiography with LA speckle tracking and plasma renalase concentration using
an enzyme-linked immunosorbent assay was performed. AF recurrence was defined as
any AF episode on seven-day electro-cardiographic monitoring at six-month follow
up. RESULTS: Renalase level was higher in the study group than in the control
group (mean 27.99 vs. 21.48 MUg/mL, p = 0.004), but it was lower in patients with
persistent AF (19.05 vs. 28.77 MUg/mL; p = 0.023) and among patients with AF
episodes di-rectly preceding PVI (24.50 vs. 29.66 MUg/mL; p = 0.04). Renalase
concentration within the first quartile was associated with higher mean heart
rate (70 vs. 61 bpm, p = 0.029), greater AF burden (36.9% vs. 9.3%, p = 0.027),
greater LA diameter (41.1 vs. 37.9 mm, p = 0.011), and a trend towards less
negative global LA strain (-9.4 vs. -13.5, p = 0.082). Logistic regres-sion
revealed that global four-chamber LA strain was the only independent predictor of
renalase variability (p = 0.0045). Renalase concentration did not predict AF
recurrence at six-month follow-up (area under curve [AUC] = 0.614, p = 0.216).
CONCLUSIONS: Low renalase level may be associated with impaired rate control,
higher AF burden, and advanced LA remodel-ling in AF patients undergoing PVI, but
it does not predict sinus rhythm maintenance.
PMID- 29944174
TI - Ten-year study of late electrotherapy complications. Single-centre analysis of
indications and safety of transvenous leads extraction.
AB - BACKGROUND: An increase in the number of cardiac implantable electronic device
(CIED) implantations is associated with a higher frequency of electrotherapy
complications. AIM: The aim of the study was to determine the risk factors for
late electrotherapy complications and to evaluate the effectiveness of
transvenous lead extraction (TLE) and survival after TLE. METHODS: We analysed
the clinical data of 225 patients with electrotherapy complications referred for
TLE in a single centre in the years 2006 to 2015. Indications for TLE, risk
factors for infectious complications, effectiveness of TLE, and survival after
the procedure were assessed. RESULTS: In the study group, non-infectious
indications for TLE predominated (78.2%). Analysis of risk for infectious
complications demonstrated the important role of chronic renal failure (hazard
ratio [HR] 1.842, p = 0.034) and a greater number of CIED-related procedures (HR
4.768, p < 0.001). High effectiveness of TLE and significantly higher long-term
mortality of patients with infectious complications compared with the remainder
(50% vs. 20%, p < 0.05) were documented. CONCLUSIONS: The study demonstrated a
high rate of patients with non-infectious complications referred for TLE and very
high effectiveness of the procedure. The worse long-term survival of patients
with infectious complications, as well as increased risk for such complications
due to the greater number of prior procedures, should prompt the consideration of
early referral for TLE in the case of lead dysfunctions.
PMID- 29944175
TI - Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in
children with comorbid tic disorders.
AB - BACKGROUND: This is an update of the original Cochrane Review published in Issue
4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of
the comorbid psychiatric disorders that complicate tic disorders. Medications
commonly used to treat ADHD symptoms include stimulants such as methylphenidate
and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants;
and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to
the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is
often of greater priority than the medical management of tics. However, for many
decades, clinicians have been reluctant to use stimulants to treat children with
ADHD and tics for fear of worsening their tics. OBJECTIVES: To assess the
effects of pharmacological treatments for ADHD in children with comorbid tic
disorders on symptoms of ADHD and tics. SEARCH METHODS: In September 2017, we
searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two
trial registers and contacted experts in the field for any ongoing or unpublished
studies. SELECTION CRITERIA: We included randomized, double-blind, controlled
trials of any pharmacological treatment for ADHD used specifically in children
with comorbid tic disorders. We included both parallel-group and cross-over study
designs. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures
of Cochrane, in that two review authors independently selected studies, extracted
data using standardized forms, assessed risk of bias, and graded the overall
quality of the evidence by using the GRADE approach. MAIN RESULTS: We included
eight randomized controlled trials (four of which were cross-over trials) with
510 participants (443 boys, 67 girls) in this review. Participants in these
studies were children with both ADHD and a chronic tic disorder. All studies took
place in the USA and ranged from three to 22 weeks in duration. Five of the eight
studies were funded by charitable organizations or government agencies, or both.
One study was funded by the drug manufacturer. The other two studies did not
specify the source of funding. Risk of bias of included studies was low for
blinding; low or unclear for random sequence generation, allocation concealment,
and attrition bias; and low or high for selective outcome reporting. We were
unable to combine any of the studies in a meta-analysis due to important clinical
heterogeneity and unit-of-analysis issues.Several of the trials assessed multiple
agents. Medications assessed included methylphenidate, clonidine, desipramine,
dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low-quality
evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality
evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the
treatment of ADHD in children with tics. All studies, with the exception of a
study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also
improved in children treated with guanfacine, desipramine, methylphenidate,
clonidine, and a combination of methylphenidate and clonidine. In one study, tics
limited further dosage increases of methylphenidate. High-dose dextroamphetamine
appeared to worsen tics in one study, although the length of this study was
limited to three weeks. There was appetite suppression or weight loss in
association with methylphenidate, dextroamphetamine, atomoxetine, and
desipramine. There was insomnia associated with methylphenidate and
dextroamphetamine, and sedation associated with clonidine. AUTHORS' CONCLUSIONS:
Following an updated search of potentially relevant studies, we found no new
studies that matched our inclusion criteria and thus our conclusions have not
changed.Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine
appear to reduce ADHD symptoms in children with tics though the quality of the
available evidence was low to very low. Although stimulants have not been shown
to worsen tics in most people with tic disorders, they may, nonetheless,
exacerbate tics in individual cases. In these instances, treatment with alpha
agonists or atomoxetine may be an alternative. Although there is evidence that
desipramine may improve tics and ADHD in children, safety concerns will likely
continue to limit its use in this population.
PMID- 29944176
TI - Multilayer Lead-Free Ceramic Capacitors with Ultrahigh Energy Density and
Efficiency.
AB - The utilization of antiferroelectric (AFE) materials is thought to be an
effective approach to enhance the energy density of dielectric capacitors.
However, the high energy dissipation and inferior reliability that are associated
with the antiferroelectric-ferroelectric phase transition are the main issues
that restrict the applications of antiferroelectric ceramics. Here,
simultaneously achieving high energy density and efficiency in a dielectric
ceramic is proposed by combining antiferroelectric and relaxor features. Based on
this concept, a lead-free dielectric (Na0.5 Bi0.5 )TiO3 -x(Sr0.7 Bi0.2 )TiO3 (NBT
xSBT) system is investigated and the corresponding multilayer ceramic capacitors
(MLCCs) are fabricated. A record-high energy density of 9.5 J cm-3 , together
with a high energy efficiency of 92%, is achieved in NBT-0.45SBT multilayer
ceramic capacitors, which consist of ten dielectric layers with the single-layer
thickness of 20 um and the internal electrode area of 6.25 mm2 . Furthermore, the
newly developed capacitor exhibits a wide temperature usage range of -60 to 120
degrees C, with an energy-density variation of less than 10%, and satisfactory
cycling reliability, with degradation of less than 8% over 106 cycles. These
characteristics demonstrate that the NBT-0.45SBT multilayer ceramic is a
promising candidate for high-power energy storage applications.
PMID- 29944177
TI - Nanoparticle@Metal-Organic Frameworks as a Template for Hierarchical Porous
Carbon Sponges.
AB - The preparation of hierarchical porous carbon sponges (HCS) from metal oxide
nanoparticle@metal-organic frameworks is reported. ZnO nanoparticles are
partially converted to zeolitic imidazolate framework-8 (ZIF-8) crystals in
presence of n-butylamine to obtain ZnO@ZIF-8 porous hybrids. After direct
carbonization, followed by ZnO acidic etching, ZnO@ZIF-8 crystals were converted
to submicrometric HCS. Due to the high surface area and accessible porosity,
combining micro- and mesoporosity of HCS, their application for the extraction of
water pollutants was studied by preparing HCS/polymer membranes, and showed a
high efficiency for the fast (650 L m-2 h-1 ) removal of plastic degradation by
products (DBP, dibutyl phthalate. DEHP, bis(2-n-ethylhexyl)phthalate). DBP and
DEHP breakthroughs were lower than 3 % after the filtration of 100 mL of water
containing simultaneously both phthalates at a high concentration level (300 MUg
L-1 , each). HCS/polymer membranes were reusable up to 5 times, maintaining their
extraction capacity, with relative errors of 6 % for DBP, and <1 % for DEHP.
PMID- 29944178
TI - Cold Sintered Ceramic Nanocomposites of 2D MXene and Zinc Oxide.
AB - Nanocomposites containing 2D materials have attracted much attention due to their
potential for enhancing electrical, magnetic, optical, mechanical, and thermal
properties. However, it has been a challenge to integrate 2D materials into
ceramic matrices due to interdiffusion and chemical reactions at high
temperatures. A recently reported sintering technique, the cold sintering process
(CSP), which densifies ceramics with the assistance of transient aqueous
solutions, provides a means to circumvent the aforementioned problems. The
efficacious co-sintering of Ti3 C2 Tx (MXene), a 2D transition carbide, with ZnO,
an oxide matrix, is reported. Using CSP, the ZnO-Ti3 C2 Tx nanocomposites can be
sintered to 92-98% of the theoretical density at 300 degrees C, while avoiding
oxidation or interdiffusion and showing homogeneous distribution of the 2D
materials along the ZnO grain boundaries. The electrical conductivity is improved
by 1-2 orders of magnitude due to the addition of up to 5 wt% MXene. The hardness
and elastic modulus show an increase of 40-50% with 0.5 wt% MXene, and over 150%
with 5 wt% of MXene. The successful densification of ZnO-MXene nanocomposite
demonstrates that the cold sintering of ceramics with 2D materials is a promising
processing route for designing new nanocomposites with a diverse range of
applications.
PMID- 29944179
TI - The Hebeloma cylindrosporum HcPT2 Pi transporter plays a key role in
ectomycorrhizal symbiosis.
AB - Through a mutualistic relationship with woody plant roots, ectomycorrhizal fungi
provide growth-limiting nutrients, including inorganic phosphate (Pi), to their
host. Reciprocal trades occur at the Hartig net, which is the symbiotic interface
of ectomycorrhizas where the two partners are symplasmically isolated. Fungal Pi
must be exported to the symbiotic interface, but the proteins facilitating this
transfer are unknown. In the present study, we combined transcriptomic,
microscopy, whole plant physiology, X-ray fluorescence mapping, 32 P labeling and
fungal genetic approaches to unravel the role of HcPT2, a fungal Pi transporter,
during the Hebeloma cylindrosporum-Pinus pinaster ectomycorrhizal association. We
localized HcPT2 in the extra-radical hyphae and the Hartig net and demonstrated
its determinant role for both the establishment of ectomycorrhizas and Pi
allocation towards P. pinaster. We showed that the host plant induces HcPT2
expression and that the artificial overexpression of HcPT2 is sufficient to
significantly enhance Pi export towards the central cylinder. Together, our
results reveal that HcPT2 plays an important role in ectomycorrhizal symbiosis,
affecting both Pi influx in the mycelium and efflux towards roots under the
control of P. pinaster.
PMID- 29944180
TI - Oxoberyllates SrBeO2 and Sr12 Be17 O29 as Novel Host Materials for Eu2+
Luminescence.
AB - Beryllate structures are marginally investigated, but show intriguing structural
relations to oxo- and nitridosilicates. A typical feature is the coordination of
Be in both trigonal planar and tetrahedral coordination by O. A broad range of
structures is accessible by variable combinations of both building units. Three
novel ternary Sr-oxoberyllates are characterized by single-crystal X-ray
diffraction analysis, density functional theory calculations and investigations
on luminescence properties: alpha-SrBeO2 , beta-SrBeO2 and Sr12 Be17 O29 are
obtained with oxoberyllate substructures, made up of either BeO3 triangles or
BeO4 tetrahedra. The compounds can be described as chain- and layer-type
beryllates. When excited with blue light of (In,Ga)N LED chips, beta-SrBeO2 and
Sr12 Be17 O29 show visible emission in the yellow and orange spectral range,
respectively, upon doping with Eu2+ . Exceptional narrow-band yellow emission
(lambdaem =564 nm, fwhm=55 nm) makes beta-SrBeO2 :Eu2+ a promising phosphor for
application in phosphor-converted (pc-)LEDs.
PMID- 29944181
TI - Photocontrol of Drug Release from Supramolecular Hydrogels with Green Light.
AB - Photoresponsive smart materials transform light energy into sophisticated
functions. They find increasing biomedical applications in light-induced drug
release and photopharmacology, because they can provide the desired therapeutic
effect locally due to precise spatiotemporal dosage control. However, the
majority of reported studies rely on cytotoxic UV light that penetrates tissues
poorly. Here, we report the first drug-releasing system based on photochromic low
molecular weight supramolecular hydrogels that is triggered with visible light.
We demonstrated green-light-induced release of structurally unmodified
antibiotic, anticancer, and anti-inflammatory drugs under physiological
conditions. Using the antibiotic-loaded gel, we selectively inhibited bacterial
growth with green light.
PMID- 29944182
TI - A Shape-Induced Orientation Phase within 3D Nanocrystal Solids.
AB - When nanocrystals self assemble into ordered superstructures they form functional
solids that may inherit the electronical properties of the single nanocrystals.
To what extent these properties are enhanced depends on the positional and
orientational order of the nanocrystals within the superstructure. Here, the
formation of micrometer-sized free-standing supercrystals of faceted 20 nm Bi
nanocrystals is investigated. The self-assembly process, induced by nonsolvent
into solvent diffusion, is probed in situ by synchrotron X-ray scattering. The
diffusion-gradient is identified as the critical parameter for controlling the
supercrystal-structure as well as the alignment of the supercrystals with respect
to the substrate. Monte Carlo simulations confirm the positional order of the
nanocrystals within these superstructures and reveal a unique orientation phase:
the nanocrystal shape, determined by the atomic Bi crystal structure, induces a
total of 6 global orientations based on facet-to-facet alignment. This parallel
alignment of facets is a prerequisite for optimized electronic and optical
properties within designed nanocrystal solids.
PMID- 29944183
TI - A Longitudinal Examination of Decisions to Ride and Decline Rides with Drinking
Drivers.
AB - BACKGROUND: Riding with a drinking driver (RWDD) is a serious concern that leads
to numerous preventable deaths every year. There is a significant gap in research
on empirically tested predictors of RWDD that could be implemented in prevention
efforts. College students are in need of such prevention efforts, as they have
some of the highest rates of alcohol-related crash fatalities and may engage in
RWDD more than their noncollege peers. This study utilized behavioral decision
making approach to examine predictors of RWDD and declining a ride from a
drinking driver (Decline) in older college students. METHODS: Students (n = 791)
in their third year of college were enrolled from 3 large and diverse
universities. Psychosocial (e.g., expectancies, norms) and decision-making
variables (willingness to RWDD and intentions to use alternatives) were assessed
in the fall of their third year. One year later, RWDD and Decline behaviors were
assessed. Zero-inflated Poisson analyses were used to assess how decision-making
variables predicted RWDD and Decline behavior. Associations between psychosocial
and decision-making variables were also assessed. RESULTS: Thirteen percent of
students reported RWDD and ~28% reported Decline behavior. Willingness to RWDD
and typical weekly drinking were both associated with increases in RWDD (odds
ratio [OR] = 1.58 and 1.40, respectively), whereas intentions to use
alternatives, sex, and ethnicity were not associated with RWDD. Only weekly
drinking was associated with Decline, with an increase in drinking associated
with increased Decline (OR = 1.48). All psychosocial variables were significantly
associated with the decision-making variables except positive expectancies.
CONCLUSIONS: Results provide evidence that willingness to RWDD is a predictor of
future RWDD, even if students intend to use safe alternatives. Future research is
needed to better understand decision-making factors that influence Decline.
Results also suggest prevention and interventions efforts, such as brief
motivational intervention, Parent-Based Interventions, and normative feedback
interventions could be adapted to reduce RWDD.
PMID- 29944184
TI - Small-animal, whole-body imaging with metamaterial-inspired RF coil.
AB - Particular applications in preclinical magnetic resonance imaging require the
entire body of an animal to be imaged with sufficient quality. This is usually
performed by combining regions scanned with small coils with high sensitivity or
long scans using large coils with low sensitivity. Here, a metamaterial-inspired
design employing a parallel array of wires operating on the principle of
eigenmode hybridization was used to produce a small-animal imaging coil. The coil
field distribution responsible for the coil field of view and sensitivity was
simulated in an electromagnetic simulation package and the coil geometrical
parameters were optimized for whole-body imaging. A prototype coil was then
manufactured and assembled using brass telescopic tubes with copper plates as
distributed capacitance. Its field distribution was measured experimentally using
the B1+ mapping technique and was found to be in close correspondence with the
simulated results. The coil field distribution was found to be suitable for large
field of view small-animal imaging and the coil image quality was compared with a
commercially available coil by whole-body scanning of living mice. Signal-to
noise measurements in living mice showed higher values than those of a
commercially available coil with large receptive fields, and rivalled the
performance of small receptive field and high-sensitivity coils. The coil was
deemed to be suitable for some whole-body, small-animal preclinical applications.
PMID- 29944185
TI - Efficiently enforcing artisanal fisheries to protect estuarine biodiversity.
AB - Artisanal fisheries support millions of livelihoods worldwide, yet ineffective
enforcement can allow for continued environmental degradation due to
overexploitation. Here, we use spatial planning to design an enforcement strategy
for a pre-existing spatial closure for artisanal fisheries considering climate
variability, existing seasonal fishing closures, representative conservation
targets and enforcement costs. We calculated enforcement cost in three ways,
based on different assumptions about who could be responsible for monitoring the
fishery. We applied this approach in the Patos Lagoon estuary (Brazil), where we
found three important results. First, spatial priorities for enforcement were
similar under different climate scenarios. Second, we found that the cost and
percentage of area enforced varied among scenarios tested by the conservation
planning analysis, with only a modest increase in budget needed to incorporate
climate variability. Third, we found that spatial priorities for enforcement
depend on whether enforcement is carried out by a central authority or by the
community itself. Here, we demonstrated a method that can be used to efficiently
design enforcement plans, resulting in the conservation of biodiversity and
estuarine resources. Also, cost of enforcement can be potentially reduced when
fishers are empowered to enforce management within their fishing grounds.
PMID- 29944186
TI - Flexible Transient Optical Waveguides and Surface-Wave Biosensors Constructed
from Monocrystalline Silicon.
AB - Optical technologies offer important capabilities in both biological research and
clinical care. Recent interest is in implantable devices that provide intimate
optical coupling to biological tissues for a finite time period and then undergo
full bioresorption into benign products, thereby serving as temporary implants
for diagnosis and/or therapy. The results presented here establish a silicon
based, bioresorbable photonic platform that relies on thin filaments of
monocrystalline silicon encapsulated by polymers as flexible, transient optical
waveguides for accurate light delivery and sensing at targeted sites in
biological systems. Comprehensive studies of the mechanical and optical
properties associated with bending and unfurling the waveguides from wafer-scale
sources of materials establish general guidelines in fabrication and design.
Monitoring biochemical species such as glucose and tracking physiological
parameters such as oxygen saturation using near-infrared spectroscopic methods
demonstrate modes of utility in biomedicine. These concepts provide versatile
capabilities in biomedical diagnosis, therapy, deep-tissue imaging, and surgery,
and suggest a broad range of opportunities for silicon photonics in bioresorbable
technologies.
PMID- 29944187
TI - pi-Phase Tin and Germanium Monochalcogenide Semiconductors: An Emerging Materials
System.
AB - Cubic pi-phase monochalcogenides (MX, M = Sn, Ge; X = S, Se) are an emerging new
class of materials that has recently been discovered. Here, their thermodynamic
stability, progress in synthetic routes, properties, and prospective applications
are reviewed. The thermodynamic stability is demonstrated through density
functional theory total energy and phonon spectra calculations, which show that
the pi-phase polytype is stable across the monochalcogenide family. To date, only
pi-phase tin monochalcogenides have been observed experimentally while pi-phase
Ge-monochalcogenides are predicted to be stable but are yet to be experimentally
realized. Various synthetic preparation protocols of pi-SnS and pi-SnSe are
described, focusing on surfactant-assisted nanoparticle synthesis and chemical
deposition of thin films from aqueous-bath compositions. These techniques provide
materials with different surface energies, which are likely to play a major role
in stabilizing the pi-phase in nanoscale materials. The properties of this newly
discovered family of semiconducting materials are discussed in comparison with
their conventional orthorhombic polymorphs. These could benefit a number of
photovoltaic and optoelectronic applications since, apart from being cubic, they
also possess characteristic advantages, such as moderately low toxicity and
natural abundance.
PMID- 29944188
TI - Creating Lineage Trajectory Maps Via Integration of Single-Cell RNA-Sequencing
and Lineage Tracing: Integrating transgenic lineage tracing and single-cell RNA
sequencing is a robust approach for mapping developmental lineage trajectories
and cell fate changes.
AB - Mapping the paths that stem and progenitor cells take en route to differentiate
and elucidating the underlying molecular controls are key goals in developmental
and stem cell biology. However, with population level analyses it is difficult -
if not impossible - to define the transition states and lineage trajectory branch
points within complex developmental lineages. Single-cell RNA-sequencing analysis
can discriminate heterogeneity in a population of cells and even identify rare or
transient intermediates. In this review, we propose that using these data, one
can infer the lineage trajectories of individual stem cells and identify putative
branch points. Clonal lineage tracing of stem cells allows one to define the
outcome of differentiation. Integrating these single cell-based approaches
provides a robust strategy for establishing and testing models of how an
individual stem cell changes through time to differentiate and self-renew.
PMID- 29944189
TI - Oral health care for patients with developmental disabilities: A survey of
Michigan general dentists.
AB - AIMS: The aim of this study to examine the level of access to dental care in
Michigan for individuals with DD and explore the dentists' practices, attitudes,
and perceived barriers to providing care to this vulnerable population. METHODS
AND RESULTS: A survey was mailed to a random sample of 1250 general dental
practitioners with an active license in the State of Michigan. The survey
included questions related to dentists' demographic information, opinion about
willingness, barriers, and training needs associated with delivering care to
children and adults with developmental disabilities. Descriptive statistics were
computed and chi-squared tests and logistic regression models analyzed the
association between predictor and key outcome variables. Results show that most
dentists treated individuals with developmental disabilities (80.3%). Respondents
who indicated that they currently do not treat these patients identified behavior
management of patient (67.9%), inadequate training and experiences (52.4%) and
severity of patient's condition (41.7%) as the most common reasons for not
providing care to individuals with developmental disabilities. CONCLUSION: A
majority of Michigan general dentists treat patients with developmental
disabilities. Addressing barriers like training and improved reimbursements might
help in increasing the number of dentists willing to treat patients with
developmental disabilities.
PMID- 29944190
TI - SNARE Complex-Associated Proteins in the Lateral Amygdala of Macaca mulatta
Following Long-Term Ethanol Drinking.
AB - BACKGROUND: Recent work with long-term ethanol (EtOH) self-administration in
nonhuman primate models has revealed a complex array of behavioral and
physiological effects that closely mimic human alcohol abuse. Detailed
neurophysiological analysis in these models suggests a myriad of pre- and
postsynaptic neurobiological effects that may contribute to the behavioral
manifestations of long-term EtOH drinking. The molecular mechanisms regulating
presynaptic effects of this chronic EtOH exposure are largely unknown. To this
end, we analyzed the effects of long-term EtOH self-administration on the levels
of presynaptic SNARE complex proteins in Macaca mulatta basolateral amygdala, a
brain region known to regulate both aversive and reward-seeking behaviors.
METHODS: Basolateral amygdala samples from control and EtOH-drinking male and
female monkeys were processed. Total basolateral amygdala protein was analyzed by
Western blotting using antibodies directed against both core SNARE and SNARE
associated proteins. We also performed correlational analyses between protein
expression levels and a number of EtOH drinking parameters, including lifetime
grams of EtOH consumed, preference, and blood alcohol concentration. RESULTS:
Significant interactions or main effects of sex/drinking were seen for a number
of SNARE core and SNARE-associated proteins. Across the range of EtOH-drinking
phenotypes, SNAP25 and Munc13-1 proteins levels were significantly different
between males and females, and Munc13-2 levels were significantly lower in
animals with a history of EtOH drinking. A separate analysis of very heavy
drinking individuals revealed significant decreases in Rab3c (females) and
complexin 2 (males). CONCLUSIONS: Protein expression analysis of basolateral
amygdala total protein from controls and animals following long-term EtOH self
administration suggests a number of alterations in core SNARE or SNARE-associated
components that could dramatically alter presynaptic function. A number of
proteins or multiprotein components were also correlated with EtOH drinking
behavior, which suggest a potentially heritable role for presynaptic SNARE
proteins.
PMID- 29944191
TI - Why Do Corals Bleach? Conflict and Conflict Mediation in a Host/Symbiont
Community.
AB - Coral bleaching has attracted considerable study, yet one central question
remains unanswered: given that corals and their Symbiodinium symbionts have co
evolved for millions of years, why does this clearly maladaptive process occur?
Bleaching may result from evolutionary conflict between the host corals and their
symbionts. Selection at the level of the individual symbiont favors using the
products of photosynthesis for selfish replication, while selection at the higher
level favors using these products for growth of the entire host/symbiont
community. To hold the selfish lower-level units in check, mechanisms of conflict
mediation must evolve. Fundamental features of photosynthesis have been co-opted
into conflict mediation so that symbionts that fail to export these products
produce high levels of reactive oxygen species and undergo programmed cell death.
These mechanisms function very well under most environmental conditions, but
under conditions particularly detrimental to photosynthesis, it is these
mechanisms of conflict mediation that trigger bleaching.
PMID- 29944192
TI - Archaea-First and the Co-Evolutionary Diversification of Domains of Life.
AB - The origins and evolution of the Archaea, Bacteria, and Eukarya remain
controversial. Phylogenomic-wide studies of molecular features that are
evolutionarily conserved, such as protein structural domains, suggest Archaea is
the first domain of life to diversify from a stem line of descent. This line
embodies the last universal common ancestor of cellular life. Here, we propose
that ancestors of Euryarchaeota co-evolved with those of Bacteria prior to the
diversification of Eukarya. This co-evolutionary scenario is supported by
comparative genomic and phylogenomic analyses of the distributions of fold
families of domains in the proteomes of free-living organisms, which show
horizontal gene recruitments and informational process homologies. It also
benefits from the molecular study of cell physiologies responsible for membrane
phospholipids, methanogenesis, methane oxidation, cell division, gas vesicles,
and the cell wall. Our theory however challenges popular cell fusion and two
domain of life scenarios derived from sequence analysis, demanding phylogenetic
reconciliation. Also see the video abstract here: https://youtu.be/9yVWn_Q9faY.
PMID- 29944193
TI - Recombinant FVIIa therapy for heavy menstrual bleeding in patients with severe FV
deficiency.
PMID- 29944194
TI - A Method for Parasagittal Sectioning for Neuroanatomical Quantification of Brain
Structures in the Adult Mouse.
AB - In this article, we present a standardized protocol for fast and robust
neuroanatomical phenotyping of the adult mouse brain, which complements a
previously published article (doi: 10.1002/cpmo.12) in Current Protocols in Mouse
Biology. It is aimed at providing an experimental pipeline within an academic
research setting from experimental work to data analysis. Our analysis focuses on
one single parasagittal plane, covering the majority of brain regions involved in
higher order cognitions such as the cortex, hippocampus, and cerebellum, for a
total of 166 parameters of area, length, and cell-level measurements in contrast
to 78 parameters in our previously published coronal screen. Benefits of using
parasagittal analysis for large-scale neuroanatomic screens are discussed. (c)
2018 by John Wiley & Sons, Inc.
PMID- 29944195
TI - Recommendations on multidisciplinary management of elective surgery in people
with haemophilia.
AB - Planning and undertaking elective surgery in people with haemophilia (PWH) is
most effective with the involvement of a specialist and experienced
multidisciplinary team (MDT) at a haemophilia treatment centre. However, despite
extensive best practice guidelines for surgery in PWH, there may exist a gap
between guidelines and practical application. For this consensus review, an
expert multidisciplinary panel comprising surgeons, haematologists, nurses,
physiotherapists and a dental expert was assembled to develop practical
approaches to implement the principles of multidisciplinary management of
elective surgery for PWH. Careful preoperative planning is paramount for
successful elective surgery, including dental examinations, physical assessment
and prehabilitation, laboratory testing and the development of haemostasis and
pain management plans. A coordinator may be appointed from the MDT to ensure that
critical tasks are performed and milestones met to enable surgery to proceed. At
all stages, the patient and their parent/caregiver, where appropriate, should be
consulted to ensure that their expectations and functional goals are realistic
and can be achieved. The planning phase should ensure that surgery proceeds
without incident, but the surgical team should be ready to handle unanticipated
events. Similarly, the broader MDT must be made aware of events in surgery that
may require postoperative plans to be changed. Postoperative rehabilitation
should begin soon after surgery, with attention paid to management of haemostasis
and pain. Surgery in patients with inhibitors requires even more careful
preparation and should only be undertaken by an MDT experienced in this area, at
a specialized haemophilia treatment centre with a comprehensive care model.
PMID- 29944196
TI - Enhancement of Thermodynamic Gas-Phase Acidity and Basicity of Water by Means of
Secondary Interactions.
AB - A series of A?water, B?water complexes (A=acid, B=base) are studied at the G4
level of theory to show that water acidity or basicity can be modulated by non
covalent interactions. Protic and non-protic acids interacting with water form
hydrogen bonds or other kinds of non-covalent interactions, respectively, that
may dramatically change the acidity of water up to almost 360 kJ ? mol-1 in terms
of enthalpy. Similarly, hydrogen bonds responsible for the interaction between
typical small nitrogen-containing Lewis bases and water can enhance the proton
affinity of water by almost 300 kJ ? mol-1 . Our results reveal that these large
enhancements are linearly related with the binding energy of the charged
complexes, and are determined by the Lewis acid-base properties of the molecule
involved in the interaction, allowing a quite precise modulation of the
corresponding acid-base properties of water.
PMID- 29944197
TI - Mitochondrial Subtype Identification and Characterization.
AB - Healthy, functional mitochondria are central to many cellular and physiological
phenomena, including aging, metabolism, and stress resistance. A key feature of
healthy mitochondria is a high membrane potential (Deltapsi) or charge
differential (i.e., proton gradient) between the matrix and inner mitochondrial
membrane. Mitochondrial Deltapsi has been extensively characterized via flow
cytometry of intact cells, which measures the average membrane potential within a
cell. However, the characteristics of individual mitochondria differ dramatically
even within a single cell, and thus interrogation of mitochondrial features at
the organelle level is necessary to better understand and accurately measure
heterogeneity. Here we describe a new flow cytometric methodology that enables
the quantification and classification of mitochondrial subtypes (via their
Deltapsi, size, and substructure) using the small animal model C. elegans. Future
application of this methodology should allow research to discern the bioenergetic
and mitochondrial component in a number of human disease and aging models,
including, C. elegans, cultured cells, small animal models, and human biopsy
samples. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29944198
TI - Colors of attraction: Modeling insect flight to light behavior.
AB - Light sources attract nocturnal flying insects, but some lamps attract more
insects than others. The relation between the properties of a light source and
the number of attracted insects is, however, poorly understood. We developed a
model to quantify the attractiveness of light sources based on the spectral
output. This model is fitted using data from field experiments that compare a
large number of different light sources. We validated this model using two
additional datasets, one for all insects and one excluding the numerous Diptera.
Our model facilitates the development and application of light sources that
attract fewer insects without the need for extensive field tests and it can be
used to correct for spectral composition when formulating hypotheses on the
ecological impact of artificial light. In addition, we present a tool allowing
the conversion of the spectral output of light sources to their relative insect
attraction based on this model.
PMID- 29944199
TI - Low-cost LED-based Photo-CIDNP Enables Biocompatible Hyperpolarization of 19 F
for NMR and MRI at 7 T and 4.7 T.
AB - Substrates containing 19 F can serve as background-free reporter molecules for
NMR and MRI. However, in vivo applications are still limited due to the lower
signal-to-noise ratio (SNR) when compared with 1 H NMR. Although
hyperpolarization can increase the SNR, to date, only photo-chemically induced
dynamic nuclear polarization (photo-CIDNP) allows for hyperpolarization without
harmful metal catalysts. Photo-CIDNP was shown to significantly enhance 19 F NMR
signals of 3-fluoro-DL-tyrosine in aqueous solution using flavins as
photosensitizers. However, lasers were used for photoexcitation, which is
expensive and requires appropriate protection procedures in a medical or lab
environment. Herein, we report 19 F MR hyperpolarization at 4.7 T and 7 T with a
biocompatible system using a low-cost and easy-to-handle LED-based set-up. First
hyperpolarized 19 F MR images could be acquired, because photo-CIDNP enabled
repetitive hyperpolarization without adding new substrates.
PMID- 29944200
TI - Complexes of Crown Ether Macrocycles with Methyl Guanidinium: Insights into the
Capture of Charge in Peptides.
AB - Crown ethers are well known as modulating agents of protein function and
interactions. The action of crown ethers is driven by an alteration of the
charged moieties of proteins through the capping of cationic amino acid side
chains. This study evaluates the conformational features involved in the binding
of crown ethers to the side chain of arginine. For this purpose, isolated
complexes of methyl guanidinium with 12-crown-4 and 18-crown-6 are characterized
with infrared action vibrational spectroscopy and quantum chemical computations.
The conformational landscapes of the two complexes comprise an extensive ensemble
of conformations close in energy. In the 12-crown-4 complex, the crown ether has
the plane of its backbone approximately perpendicular to that of the guanidinium
moiety and coordinates to two or three of its NHdelta+ bonds. In the 18-crown-6
complex, the crown ether backbone is partially folded and tilted with respect to
guanidinium and fixes its position in order to facilitate up to a four-fold
coordination in the complex. The access of the complexes to multiple
conformations leads to broad band structures in the N-H stretching region of
their vibrational spectra.
PMID- 29944201
TI - Multicombination Approach Suppresses Listeria monocytogenes-Induced Septicemia
Associated Acute Hepatic Failure: The Role of iRhom2 Signaling.
AB - The mortality rate of acute liver failure significantly increases due to fatal
septicemia. Inactive rhomboid protein 2 (iRhom2) is an essential regulator of
shedding TNF-alpha by trafficking with TNF-alpha converting enzyme (TACE).
Fisetin, a flavonoid present in various fruits and plants, possesses anti
oxidative stress and anti-inflammatory activities. Here, multi-combination
nanoparticles Fe@Au conjugated with fisetin, iRhom2 small interfering RNA
(siRNA), and TNF-alpha inhibitor (FN) are prepared to examine their effects on
fatal septicemia-associated hepatic failure induced by Listeria monocytogenes
(LM) in mice and to reveal the underlying mechanisms. After LM infection,
upregulation of glutamic-oxalacetic transaminease, glutamic-pyruvic transaminase,
alkaline phosphatase, TNF-alpha, malondialdehyde, H2 O2 , and O2- is
observedcompared to FN-treated mice. The iRhom2/TACE/TNF-alpha signals are
enhanced in vivo and in vitro, resulting in oxidative stress, which is especially
associated with the activation of kupffer cells and other macrophages. Decrease
in Nrf2 activation and increase of inflammation-associated regulators are also
noted in vivo and in vitro. Furthermore, overexpression of TNF-alpha derived from
macrophages aggravates hepatic failure. Inversely, the processes above are
restored by FN nanoparticles through the regulation of the iRhom2/TACE/TNF-alpha
axis and Nrf2 activation. These findings suggest that FN may be a potential
approach to protect against bacterial septicemia-related diseases by targeting
iRhom2.
PMID- 29944202
TI - Multiphoton Intravital Calcium Imaging.
AB - Multiphoton intravital calcium imaging is a powerful technique that enables high
resolution longitudinal monitoring of cellular and subcellular activity hundreds
of microns deep in the living organism. This unit addresses the application of 2
photon microscopy to imaging of genetically encoded calcium indicators (GECIs) in
the mouse brain. The protocols in this unit enable real-time intravital imaging
of intracellular calcium concentration simultaneously in hundreds of neurons, or
at the resolution of single synapses, as mice respond to sensory stimuli or
perform behavioral tasks. Protocols are presented for implantation of a cranial
imaging window to provide optical access to the brain and for 2-photon image
acquisition. Protocols for implantation of both open skull and thinned skull
windows for single or multi-session imaging are described. (c) 2018 by John Wiley
& Sons, Inc.
PMID- 29944203
TI - A DNA-Mediated Chemically Induced Dimerization (D-CID) Nanodevice for Nongenetic
Receptor Engineering To Control Cell Behavior.
AB - Small-molecule regulation is a powerful switching tool to manipulate cell signal
transduction for a desired function; however, most available methods usually
require genetic engineering to endow cells with responsiveness to user-defined
small molecules. Herein, we demonstrate a nongenetic approach for small-molecule
controlled receptor activation and consequent cell behavior manipulation that is
based on DNA-mediated chemically induced dimerization (D-CID). D-CID uses a
programmable chemical-responsive DNA nanodevice to trigger DNA strand
displacement and induce the activation of c-Met, a tyrosine kinase receptor
cognate for hepatocyte growth factor, through dimerization. Through the use of
various functional nucleic acids, including aptamers and DNAzymes, as recognition
modules, the versatility of D-CID in inducing c-Met signaling upon addition of
various small-molecular or ionic cues, including ATP, histidine, and Zn2+ , is
demonstrated. Moreover, owing its multi-input properties, D-CID can be used to
manipulate the behaviors of multiple cell populations simultaneously in a
selective and programmable fashion.
PMID- 29944204
TI - Co-immobilized Whole Cells with omega-Transaminase and Ketoreductase Activities
for Continuous-Flow Cascade Reactions.
AB - An improved sol-gel process involving the use of hollow silica microspheres as a
supporting additive was applied for the co-immobilization of whole cells of
Escherichia coli with Chromobacterium violaceum omega-transaminase activity and
Lodderomyces elongisporus with ketoreductase activity. The co-immobilized cells
with two different biocatalytic activities could perform a cascade of reactions
to convert racemic 4-phenylbutan-2-amine or heptan-2-amine into a nearly
equimolar mixture of the corresponding enantiomerically pure R amine and S
alcohol even in continuous-flow mode. The novel co-immobilized whole-cell system
proved to be an easy-to-store and durable biocatalyst.
PMID- 29944205
TI - Monolayer AsTe2 : Stable Robust Metal in 2D, 1D and 0D.
AB - The structural, phononic, and electronic properties of the monolayer structures
of AsTe2 are characterized by performing density functional theory (DFT)
calculations. Total energy optimization and phonon calculations reveal that
single layers of the 2H-AsTe2 and 1T-AsTe2 phases form dynamically stable crystal
structures. Electronic structure analysis also shows that both 2H and 1T phases
have nonmagnetic metallic character. It is also predicted that the metallic
nature of the ultra-thin both 2H-AsTe2 and 1T-AsTe2 structures remain unchanged
even under high biaxial strain values. For further examination of the
dimensionality effect in the robust metallicity in 2D AsTe2 phases, electronic
characteristics of 1D nanoribbons and 0D quantum dots are also investigated. It
is found that independent from the dimension and crystallographic orientations 0D
and 1D structures of 2H- and 1T-AsTe2 structures have metallic behavior. It is
found that single layers of AsTe2 are quite promising materials for nanodevice
applications owing to the robust metallic character.
PMID- 29944206
TI - A Compact Head-Mounted Endoscope for In Vivo Calcium Imaging in Freely Behaving
Mice.
AB - Miniaturized fluorescence microscopes for imaging calcium transients are a
promising tool for investigating the relationship between behavior and population
level neuronal activity in rodents. However, commercially available miniature
microscopes may be costly and, because they are closed source, may not be easily
modified based on particular experimental requirements. Here, we describe how to
build and use a low-cost compact head-mounted endoscope (CHEndoscope) system for
in vivo calcium imaging. The CHEndoscope uses an implanted gradient index lens
along with the genetically encoded calcium indicator GCaMP6 to image calcium
transients from hundreds of neurons simultaneously in awake behaving mice. This
system is affordable, open source, and flexible, permitting modification
depending on the particular experiment. This article describes in detail the
assembly, surgical implantation, data collection, and processing of calcium
signals using the CHEndoscope system. The aim of this open framework is to
provide an accessible set of miniaturized calcium imaging tools for the
neuroscience research community. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29944207
TI - The Combination of Hydrogen and Methanol Production through Artificial
Photosynthesis-Are We Ready Yet?
AB - Because 100 % quantum efficiency for the photosynthetic production of H2 from H2
O under visible illumination has been achieved recently, the oxidation of H2 O to
O2 remains the bottleneck to the overall water-splitting reaction. Oxidation of
CH4 to CH3 OH might be combined with water reduction instead, so that H2 and CH3
OH chemical fuels can be simultaneously produced through a one-step process under
solar illumination. This combination would be a promising approach towards a more
sustainable future of chemistry, in which developing different strategies for
artificial photosynthesis is of paramount importance. By using free and adsorbed
HO. radicals on the semiconductor surface, CH4 can be activated to H3 C. radicals
and converted into CH3 OH, respectively, with great selectivity up to 100 %. The
present lack of efficient photosynthetic systems for the formation of H2 and CH3
OH from abundant H2 O and CH4 motivates future research for basic science and
industrial applications.
PMID- 29944208
TI - A Peri-tetracene Diradicaloid: Synthesis and Properties.
AB - Peri-acenes are good model compounds for zigzag graphene nanoribbons, but their
synthesis is extremely challenging owing to their intrinsic open-shell diradical
character. Now, the successful synthesis and isolation of a stable peri-tetracene
derivative PT-2ClPh is reported; four 2,6-dichlorophenyl groups are attached onto
the most reactive sites along the zigzag edges. The structure was confirmed by X
ray crystallographic analysis and its electronic properties were systematically
investigated by both experiments and theoretical calculations. It exhibits an
open-shell singlet ground state with a moderate diradical character (y0 =51.5 %
by calculation) and a small singlet-triplet gap (DeltaES-T =-2.5 kcal mol-1 by
SQUID measurement). It displays global aromatic character, which is different
from the smaller-size bisanthene analogue BA-CF3.
PMID- 29944209
TI - Genome-wide screening of long non-coding RNAs involved in rubber biosynthesis in
Eucommia ulmoides.
AB - Increasing evidence indicates that long non-coding RNAs (lncRNAs) play pivotal
roles in regulatory networks controlling plant and animal gene expression.
However, lncRNA roles in regulating rubber biosynthesis in Eucommia ulmoides, an
emerging source of natural rubber (Eu-rubber), are currently unknown. Here, we
report on RNA deep-sequencing of E. ulmoides fruits at two developmental stages.
Based on application of a stringent pipeline, 29,103 lncRNAs and 9,048
transcripts of uncertain coding potential (TUCPs) were identified. Two
differentially expressed (DE) TUCPs appear to simultaneously regulate 12 protein
coding genes involved in Eu-rubber biosynthesis (GIEBs), as well as 95 DE genes.
Functional categorization of these 95 DE genes indicated their involvement in
subcellular microstructures and cellular processes, such as cell wall, cell
division, and growth. These DE genes may participate in the differentiation and
development of laticifers, where Eu-rubber is synthesized. A model is proposed in
which "commanders" (DE TUCPs) direct the "builders" (DE genes) to construct a
"storehouse" of materials needed for Eu-rubber synthesis, and the "workers"
(GIEBs) to synthesize Eu-rubber. These findings provide insights into both cis-
and trans-polyisoprene biosynthesis in plants, laying the foundation for
additional studies of this crucial process.
PMID- 29944210
TI - Cell migration in the Xenopus gastrula.
AB - Xenopus gastrulation movements are in large part based on the rearrangement of
cells by differential cell-on-cell migration within multilayered tissues.
Different patterns of migration-based cell intercalation drive endoderm and
mesoderm internalization and their positioning along their prospective body axes.
C-cadherin, fibronectin, integrins, and focal contact components are expressed in
all gastrula cells and play putative roles in cell-on-cell migration, but their
actual functions in this respect are not yet understood. The gastrula can be
subdivided into two motility domains, and in the vegetal, migratory domain, two
modes of cell migration are discerned. Vegetal endoderm cells show ingression
type migration, a variant of amoeboid migration characterized by the lack of
locomotory protrusions and by macropinocytosis as a mechanism of trailing edge
resorption. Mesendoderm and prechordal mesoderm cells use lamellipodia in a
mesenchymal mode of migration. Gastrula cell motility can be dissected into
traits, such as cell polarity, adhesion, mobility, or protrusive activity, which
are controlled separately yet in complex, combinatorial ways. Cells can
instantaneously switch between different combinations of traits, showing
plasticity as they respond to substratum properties. This article is categorized
under: Early Embryonic Development > Gastrulation and Neurulation.
PMID- 29944211
TI - OsPKpalpha1 encodes a plastidic pyruvate kinase that affects starch biosynthesis
in the rice endosperm.
AB - Pyruvate kinase (PK) is a key enzyme in glycolysis and carbon metabolism. Here,
we isolated a rice (Oryza sativa) mutant, w59, with a white-core floury
endosperm. Map-based cloning of w59 identified a mutation in OsPKpalpha1, which
encodes a plastidic isoform of PK (PKp). OsPKpalpha1 localizes to the amyloplast
stroma in the developing endosperm, and the mutation of OsPKpalpha1 in w59
decreases the plastidic PK activity, resulting in dramatic changes to the lipid
biosynthesis in seeds. The w59 grains were also characterized by a marked
decrease in starch content. Consistent with a decrease in number and size of the
w59 amyloplasts, large empty spaces were observed in the central region of the
w59 endosperm, at the early grain-filling stage. Moreover, a phylogenetic
analysis revealed four potential rice isoforms of OsPKp. We validated the in
vitro PK activity of these OsPKps through reconstituting active PKp complexes
derived from inactive individual OsPKps, revealing the heteromeric structure of
rice PKps, which was further confirmed using a protein-protein interaction
analysis. These findings suggest a functional connection between lipid and starch
synthesis in rice endosperm amyloplasts.
PMID- 29944212
TI - Ion-Selective Prussian-Blue-Modified Celgard Separator for High-Performance
Lithium-Sulfur Battery.
AB - Application of Li-S batteries has been restricted because of their major problem,
that is, shuttling of soluble polysulfides between electrodes, which results in
serious capacity fading. For the development of high-performance Li-S batteries,
we first time utilize a simple growth method to introduce a Prussian blue (PB)
modified Celgard separator as an ion-selective membrane. The unique structure of
PB could effectively suppress the shuttle of polysulfides but scarcely affect the
transfer ability of lithium ions, which is beneficial to achieve high sulfur
conversion efficiency and capacity retention. The Li-S battery with PB-modified
Celgard separator has an average capacity decay of only 0.03 % per cycle at 1 C
after 1000 cycles.
PMID- 29944213
TI - Assessing Individual Neuronal Activity Across the Intact Brain: Using
Hybridization Chain Reaction (HCR) to Detect Arc mRNA Localized to the Nucleus in
Volumes of Cleared Brain Tissue.
AB - Arc (activity-regulated cytoskeleton-associated protein) is an immediate early
gene that may be used to label recently active neurons. Arc is transcribed
following neuronal activity, and its mRNA is then rapidly transported to
dendrites. This feature allows nuclear-localized Arc mRNA to define ensembles of
recently active neurons in systems or circuit neuroscience. However, typical in
situ hybridization techniques severely constrain the thickness of the tissue
specimen (typically 20-um brain slices). Here, we describe a protocol for
visualizing intranuclear Arc mRNA in large (4 * 4 * 3 mm) volumes of intact mouse
brain tissue. We combined a tissue clearing protocol (iDISCO+) with an advanced
in situ hybridization technique (hybridization chain reaction [HCR]) to detect
nuclear-localized Arc mRNA in whole, intact brain regions without the need for
brain sectioning or reconstruction. We successfully applied this protocol to
image ensembles of neurons of the basolateral amygdala in mice that are active
following the recall of a conditioned fear memory. (c) 2018 by John Wiley & Sons,
Inc.
PMID- 29944214
TI - Bastard Breadfruit and other Cheap Provisions: Early Food Science for the Welfare
of the Lower Orders.
AB - Breadfruit is best known in connection with an infamously failed project: the
1789 mutiny against the Bounty, commanded by William Bligh. However, four years
later, Bligh returned to the Pacific and fulfilled his commission, delivering
breadfruit and other Pacific foods to Caribbean plantations. Placing these plant
transfers in the emerg- ing sciences of food and nutrition in the eighteenth
century, this essay examines the broader political project of what would much
later be called 'the welfare state; which motivated British officials' interest
in experimenting with novel ingredients and recipes to cheaply nourish a range of
dependent populations in institutional settings. Perhaps most strikingly, their
nutritional recommendations borrowed directly from agricultural practices,
particularly from new methods for feeding livestock in confinement.
PMID- 29944215
TI - We're still here!
PMID- 29944216
TI - Child vaccination: 'A slow erosion'?.
PMID- 29944217
TI - Giving a little extra support.
PMID- 29944218
TI - A reason to Smile.
PMID- 29944219
TI - Retinoblastoma: Can you see it?.
PMID- 29944220
TI - Clinical update: Non-epileptic attack disorder.
PMID- 29944221
TI - Critical reflections on early career research development in public health
nursing.
AB - Clinical academic careers for nurses, midwives and allied health professionals
are gaining recognition internationally and nationally, yet public health nurses
appear underrepresented. The purpose of this paper is to share our learning
through a clinical-academic partnership. We critique our experiences and in the
context of public health nursing, share some of the challenges we experienced. We
aim to build on a capability framework for early career research development,
applying it specifically to public health nursing. In so doing, we hope to
provide insight and motivation for public health nurses seeking to engage with
research through clinical academic career opportunities. Our experience shows
that the framework can be useful in identifying strengths, but also capabilities
that need to be developed. We recognise that uncertainties about public health
nursing roles may limit individual wherewithal for continuing professional
development. Nonetheless, we recommend public health nurses consider clinical
academic careers to advance research in practice.
PMID- 29944222
TI - Exploring the benefits of Smile4life training: Findings from a pilot study.
AB - Smile4life is Scotland's national oral health improvement programme for people
experiencing homelessness. Following an oral health and psychosocial needs
assessment of 853 homeless people across Scotland, the Smile4life intervention
was developed and rolled out across all NHS boards. Dental health and health and
social care practitioners were invited to attend a training event at the launch
of the Smile4life: Guide for Trainers - a training guide for practitioners
working with homeless people. This paper presents results from HoPSCOTCH, a pilot
study that took place in four NHS boards to examine the benefits of training for
practitioners regarding their awareness of homelessness and the oral health needs
of homeless people. Dental health (baseline: 10; follow-up: 8) and health and
social care practitioners (baseline: 13; follow-up: 12) completed questionnaires
about their knowledge, attitudes and behaviours. The results showed that there
were increases in practitioner knowledge, confidence and motivation to help
service users access dental care, to provide oral health education and to use
motivational interviewing. The authors recommend that future training for
practitioners who work with homeless people should include communication skills
and advice on how to deliver tailored interventions, with the aim of
strengthening practitioners' confidence and motivation to deliver the Smile4life
intervention.
PMID- 29944223
TI - Improving the chance of successful implantation - part I - embryo attachment to
the endometrium and adequate trophoblast invasion.
AB - : The first in a series on improving embryo implantation is presented with
emphasis on embryo attachment and trophoblast invasion. PURPOSE: To present
knowledge of events needed for embryo attachment to the endometrium and
subsequent trophoblast invasion and uterine remodeling leading to successful
pregnancy. MATERIALS AND METHODS: Based on normal events, some practical
suggestions are proposed as to possible means of improving pregnancy rates by
enhancing possible embryo attachment and trophoblast invasion. RESULTS: Potential
benefits of achieving adequate serum estradiol levels at peak follicular
maturation, and the benefits of progesterone in the luteal phase are discussed.
Also the potential benefits of purposeful endometrial injury is considered.
CONCLUSIONS: Knowledge of the events leading to embryo attachment and trophoblast
invasion could lead to novel research ideas helping to improve pregnancy rates in
addition to proper hormone supplementation and endometrial biopsy.
PMID- 29944224
TI - Flemish obstetricians' personal preference regarding induction of labor and mode
of delivery in term births.
AB - INTRODUCTION: In a 2002 survey, 2% of Flemish gynecologists preferred elective
cesarean section for themselves or their partner. This study aims to determine
actual preference regarding induction of labor and mode of delivery in term
cephalic or breech births for gy- necologists or their partners. MATERIALS AND
METHODS: An anonymous postal questionnaire was sent to all gynecologists and
trainees in Flanders. RESULTS: Response rate was 28.2 % (241/852). In case of an
uncomplicated cephalic singleton pregnancy, 39 gynecologists (16.2%) preferred
cesarean section. Most (n=134, 66.5%) chose induction at 41 weeks, 26 (13%) at 40
weeks, 37 (18%) at 42 weeks, 26 (13%) at 40 weeks, three (1.5%) preferred
induction before 40 weeks and two (1%) would wait until after 42 weeks.
Concerning term breech, 30% (n=72) opted for vaginal delivery and 70% (n = 169)
for planned cesarean section. Ninety-nine (41%) gynecologists pre- ferred to
attempt external version first. Only 115 (47.7 %) gynecologists felt
professionally capable to assist vaginal breech delivery them- selves; about one
third (n=96; 38%) had performed less than ten vaginal breech deliveries in their
career. CONCLUSIONS: Flemish gynecologists are still in favor of vaginal delivery
for themselves in terms of cephalic position, but an increasing number favor
planned cesarean section. Most Flemish gynecologists opt for cesarean section for
themselves or their partners in case of term breech and state that they do not
feel capable in assisting vaginal breech delivery for their patients.
PMID- 29944225
TI - HELLP syndrome is still a serious, life-threatening complication of pregnancy:
admission of 34 women to an eastern Turkish intensive care unit.
AB - OBJECTIVE: The transfer of the obstetric patient to the intensive care unit is
considered as an indicator of maternal morbidity. The most important two
indications for admittance of the obstetric patient to the intensive care unit
are postpartum hemorrhage and hypertensive disorders. The purpose of this study
was to determine maternal morbidity and mortality rates in patients diagnosed
with hemolysis, elevated liver enzyme levels, and low platelet count (HELLP)
syndrome who required intensive care. MATERIALS AND METHODS: The charts of 34
patients who were diagnosed with HELLP syndrome and treated in intensive care
unit between the years 2005 - 2013 were evaluated retrospectively. RESULTS:
During the study period, a total of 151 patients were diagnosed with HELLP
syndrome and 34 patients were admitted to the intensive care unit. Mean age of
the patients was 28.97 +/- 7.26 years and there was no significant difference be-
tween survivors and non-survivors (p = 0.442). There were no significant
differences between survivors and non-survivors in terms of gestational age,
parity, and multiparity rates (p > 0.05). There was 31.2% mortal cases and 77.8%
of living cases had received regular antenatal follow-up and the difference was
statistically significant (p = 0.006). 30 patients (88.2%) required invasive
mechanical ven- tilation. The average Glasgow Coma Score (GCS) of patients was
6.47 +/- 4.34. There were significant differences between patients who lived and
who died in terms of Acute Physiology and Chronic Health Evaluation II (APACHE
II), Sequential Organ Failure Assessment (SOFA) score, and duration of invasive
mechanical ventilation (p < 0.05). Twenty-two patients (64.7%) required
transfusion of blood and blood products. Maternal mortality occurred in 16
patients (47%). The causes of death were: intracerebral hemorrhage in six cases,
acute respiratory distress syndrome (ARDS) in three cases, disseminated
intravascular coagulation (DIC) in three?cases, sepsis/multi- ple organ
dysfunction syndrome (MODS) in two cases, hepatic rupture in one case, and
massive pulmonary embolism in one case. Con- clusion: HELLP syndrome is still one
of the most serious and life-threatening complications of pregnancy. Mortality
rate can be reduced by regular antenatal follow-up and transfer of pregnant women
who carry risk to the intensive care unit without delay.
PMID- 29944226
TI - Rupture risk factors of fallopian tubal pregnancy.
AB - The present authors analyzed patients' backgrounds and pre-surgical findings to
clarify the risk factors of rupture of fallopian tubal pregnancy. The surgical
findings 113 cases were clearly diagnosed as fallopian tubal pregnancy with or
without rupture. Twenty-six cases of fallopian tubal pregnancy were ruptured and
87 cases were not ruptured at the time of operation. The risk factors of
fallopian tubal rupture were assessed by Chi-square for independence test and
multiple regression analysis. Obesity (BMI over 26), prior birth history, social
welfare entitlement, ultrasonography findings of fetal heart movement, and pre
surgical serum beta-hCG level more than 3,000 mIU/ml patient were significantly
higher risk in fallopian tubal rupture. Fertility treatment patient were at
significantly lower risk for fallopian tubal rupture. Higher beta-hCG levels,
especially >3,000 mIU/ml is associated with increased risk of fallopian tubal
rupture in ectopic pregnancy.
PMID- 29944227
TI - Urethral instillations of clobetasol propionate and lidocaine: a promising
treatment of urethral pain syndrome.
AB - PURPOSE: To evaluate topical treatment with clobetasol propionate and lidocaine
in women with urethral pain syndrome (UPS) in a retrospective pilot study.
MATERIALS AND METHODS: Urethral instillations of two ml clobetasol propionate
cream and two ml lidocaine gel in 30 Caucasian women age 15-74 years with UPS
between 1999 and 2006 were evaluated retrospectively. Instillations were given ap
proximately once a week until the patient improved. Between one and 15 (median
three) instillations were given. In substudy I a review was undertaken of the
medical records to register the treatment effect at the end of the treatment (the
last instillation) and any relapses six months thereafter. Substudy II was a
follow-up at least five years after last instillation based on medical records
and a written ques- tionnaire. RESULTS: Substudy I (n=30): By the end of the
treatment 18 women had no symptoms and 12 were improved. Five patients had
relapsed within six months. Substudy II (n=28): Twenty-eight women responded to
the questionnaire. Four women remained with no symptoms, 18 remained improved,
and six had the same symptoms as before treatment. Twenty women thought the
treatment was very effective, five rather effective, and three women reported
poor effect. Twenty-six women would ask for retreatment if a relapse oc- curred,
two patients would not. No side effects, except transient pain, were reported.
CONCLUSIONS: This retrospective study and long- term follow-up suggests that
urethral instillation of clobetasol propionate and lidocaine is effective in
treating women with UPS. Randomized control studies are warranted.
PMID- 29944228
TI - The influence of sperm parameters on the outcome of intracytoplasmic sperm
injection-embryo transfer cycle in poor responder women under 35 years of age.
AB - : To evaluate the influence of sperm parameters on the outcome of
intracytopiasmic sperm injection (ICSI) cycies in poor responaer women under the
age of 35 years in a retrospective analysis in a fertility center. MATERIALS AND
METHODS: A total of 432 poor responder women who underwent ICSI cycles were
evaluated. The interventions included ICSI and microdissection testicular sperm
extraction (m-TESE). Main outcome measures included fertilization, cleavage,
clinical pregnancy, and delivery rates. RESULTS: Patients were di- vided into
four groups according to the sperm parameters and the source of sperm; testicular
spermatozoa obtained from men with azoospermia (group 1; n=26), severe
oligoasthenoteratozoospermia (OAT) (group 2; n=35), OAT (group 3; n=104), and
normal semen analysis (group 4; n=267). Average age of the women, antral follicle
count, FSH level, male age, number of previous ICSI cycles, duration of
infertility, and the maximal endometrial thickness were similar among the groups.
In group 1, the fertilization rate was lower than those in all other groups.
Cleavage, clinical pregnancy, and delivery rates were similar among the groups.
CONCLUSIONS: Neither sperm parameters nor the source of spermatozoa affects
delivery rate through ICSI in poor responder women < 35-years-old.
PMID- 29944229
TI - Clinico-biochemical characteristics of 229 Portuguese infertile women with
polycystic ovary syndrome: clinical relevance and relationship with fertility
treatment results.
AB - PURPOSE: Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-age
women. The authors aimed to evaluate the characteristics of PCOS women and its
relationship with fertility treatment outcomes. MATERIALS AND METHODS: The
authors reviewed records of PCOS women assisted at Hospital Santa Maria.
Fertility treatment results were assessed as pregnancy rate, number of cycles,
and miscarriage rate. RESULTS: They identified 229 PCOS women, 179 (78.2%) had
waist circumference > 80 cm, 72 (31.4%) had type 2 diabetes mellitus (T2DM)
familial history and glucose abnormalities, hypertriglyceridemia and low
cholesterol-HDL were detected in 23(10.1%), 15 (6.6%) and 103 (45.0%),
respectively. Pregnancy was achieved in 164 women. The mean number of cycles to
achieve pregnancy was 2.7 (+/-2.2). Statistical analysis identified factors
associated with longer/higher number of treatments: primary infertility, T2DM
familial history, hypertriglyceridemia, and low cholesterol-HDL. Waist
circumference > 80 cm, older age, and increased LH level were associated with
miscarriage. CONCLUSIONS: Primary infertility, T2DM familial history,
hypertriglyceridemia, low cholesterol-HDL, older age, waist circumference > 80
cm, and high LH may confer poorer fertility treatment results.
PMID- 29944230
TI - Addition of low-dose hCG to rFSH during ovarian stimulation for IVF/ICSI: is it
beneficial?
AB - PURPOSE: The aim of the study was to assess the eftect ot the addition or iow
cose numan cnononic gonauoiropm (hCG) to ovarian stimulation with recombinant
follicle stimulating hormone (rFSH) on in vitro fertilization/intracytoplasmic
sperm injection (IVF/ICSI) outcome. MATERIALS AND METHODS: This retrospective
clinical study was conducted on 141 women undergoing ICSI through a short GnRH
agonist protocol with rFSH and the addition of low-dose (100 IU/day) hCG. The
control group consisted of 124 women undergoing ovarian stimulation with a
similar protocol devoid of hCG. Statistical analysis in the study population
along with a subgroup analysis for age 35 years and 36 years was performed.
RESULTS: Women in hCG group were statistically significant older and with higher
basal FSH compared to control group. This can be attributed to the Centre's
latent tendency to add hCG in the stimulation protocol in poor prognosis
patients. Despite this fact and the fact that several ovarian stimulation
parameters, such as peak estradiol levels, number of oocytes retrieved, number of
mature oocytes, and fertilization rates were in favor of the control group, the
quality of transferred embryos and pregnancy rates were in favor of hCG group.
Similar results were obtained in the subgroup analyses apart from peak estradiol
levels, which did not differ among the study groups. CONCLUSIONS: The addition of
hCG to rFSH may be associated with better quality embryos and higher pregnancy
rates, even in women of advanced reproductive age with higher basal FSH levels,
which are often considered to have poorer ovarian reserve.
PMID- 29944231
TI - Serum carcinogenic antigen (CA)-125 and CA 19-9 combining pain score in the
diagnosis of pelvic endometriosis in infertile women.
AB - OBJECTIVE: To define the utility of serum carcinogenic antigen (CA)-125 and CA 19
9 combining pain score in the prediction of pelvic endometriosis in infertile
women. MATERIALS AND METHODS: Serum CA-125 and CA 19-9 were measured using
immunoradiologic methods during the follicular phase preceding laparoscopy for
infertility. Values obtained were correlated with the occurrence and severity of
endometriosis. Receiver operating characteristic (ROC) curve was applied to
assess the utility of serum CA-125, CA 19-9, and pain score in preoperative
preparation. Cut-off value of CA-125 and CA 19-9 was defined. RESULTS: The study
enrolled 294 infertile women receiving laparoscopy between July 2010 and
September 2011. Ninety-four patients were diagnosed with endometriosis and 200
patients without. Preoperative serum CA-125 and CA 19-9 levels were significantly
different between the two groups. ROC curve analyses of serum CA-125 and CA 19-9
set a cut-off value of 18.25 IU/ml and 13.15 IU/ml, producing a sensitivity of
64.8% and 84.8%, a specificity of 81.9% and 51.6%, a positive predictive value
(PPV) of 63.6% and 46.1%, and a negative predictive value (NPV) of 81.0% and
87.4%, respectively. Combined-analyses of CA-125 and CA 19-9 produced a
sensitivity of 72.4%, a specificity of 81.9%, a PPV of 62.3%, and a NPV of 81.8%.
Combined-analyses of serum CA-125, CA 19-9 and pain score produced a sensitivity
of 71.0% and a specificity of 74.0%. CONCLUSIONS: Preoperative CA-125 and CA 19-9
levels combining pain score can be useful for the prediction of pelvic
endometrinsis and may he included in the evaluation of unexulained infertile
women.
PMID- 29944232
TI - Impacts of maternal anxiety on non-stress test parameters.
AB - OBJECTIVE: To determine the association between antenatal maternal anxiety with
non-stress test (NST) parameters, which is an indi- cator test of fetal well
being in the third trimester. MATERIALS AND METHODS: Between January and December
of 2013, 212 pregnant women, with 36-41 weeks of gestation were assessed with
measures of distress and anxiety with Beck Anxiety Inventory (BAI) and with NST.
The new National Institute Child Health and Human Development (NICHD) 2008
guideline criteria were used for interpretation of NST. Anxiety scores were
grouped as minimal, mild, moderate, and severe. The impact of anxiety on NST
parameters were investigated. RESULT: Anxiety scores were inversely correlated
with fetal heart rate (FHR) accelerations (r = -0.631, and r = -0.855), number of
fetal movements (r = -0.633, r = -0.860), FHR variability scores (r = -0.650, r =
-0.877). and NST scores (r = -0.505, r = 0.729), (for all p < 0.001). NST scores
were lower in severe anxiety group than the others. CONCLUSION: The study showed
that severe form of anxiety significantly affects NST parameters in near-term
pregnancies.
PMID- 29944233
TI - Management of bladder endometriosis with combined transurethral and laparoscopic
approach. Follow-up of pain control, quality of life, and sexual function at 12
months after surgery.
AB - To describe the pre-surgical and post-surgical outcomes at one year in terms of
recurrence of lower urinary tract symptoms, quality of life, and sexual function
of a transurethral and laparoscopic combined approach in the treatment of bladder
endometriosis. The au- thors performed a prospective observational study of 16
women affected by symptomatic bladder endometriosis at the University Hos- pitals
of Cagliari, Padua, and Foggia. In all patients bladder nodule was excised with a
transurethral and laparoscopic combined approach technique. Intensity of lower
urinary tract symptoms (VAS score) were assessed pre- and post-operatively at
one, six, and 12 months after surgery; quality of life (SF-36) and sexual
functions (FSFI) were collected preoperatively and one year postoperatively.
Operative time was 120.18 +/- 15.77 minutes and mean blood loss was 65.12 +/-
44.74. No intraoperative and postoperative complications and conversion
laparotomy occurred. Intensity of lower urinary tract symptoms evaluated with VAS
score were significantly lower after one, six, and 12 months postsurgery vs.
presurgery (p < 0.001). The authors observed a significantly improvement in the
quality of life and sexual functions in all patients at one year after surgery.
This surgical approach is safe and simple in the treatment of bladder en-
dometriosis, with low risks and optimal resolution of symptoms, and improvement
of quality of life and sexual function.
PMID- 29944234
TI - Is maternal Vitamin D associated with gestational diabetes mellitus in pregnant
women in Cyprus?
AB - BACKGROUND: There are conflicting results about the relationship between Vitamin
D deficiency (VDD) and gestational diabetes mellitus (GDM). AIM: The aim of the
study was to determine the association between 25 hydroxy vitamin D levels and
GDM in Turkish Cypriot pregnant women. STUDY DESIGN: The authors conducted a
prospective case-control study. MATERIALS AND METHODS: The authors analysed serum
250HD concentrations in 230 pregnant women between 2013-2014 in the winter period
(November-April). Twenty- five hydroxy vitamin D was measured at the time of
glucose tolerance testing at mid-gestation (24-26 weeks of pregnancy), in a popu-
lation at increased risk for GDM. Patients were than divided in to two groups:
pregnant women with GDM and pregnant women without GDM. RESULTS: The mean level
of 25 hydroxy vitamin D in the study group was 21.9 +10.4 ng/ml. Pregnant women
were diagnosed as having vitamin D insufficiency. The level of 25 hydroxy vitamin
D in women with and without GDM were 22.3 +/- 10.7 ng/dl and 20.3 +/- 9.3 ng/dl,
respectively (p = 0.262). CONCLUSION: The present study showed 250HD
insufficiency in pregnant women at midgestation which was not associated with
GDM.
PMID- 29944235
TI - Obstetric outcomes of intramural leiomyomas in pregnancy.
AB - AIM: The authors aimed to study larger intramural leiomyoma with a size of >=
three cm on pregnancy outcome of singleton pregnancies compared with control
group. MATERIALS AND METHODS: The hospital records of all pregnancies followed
between years of 2009 and 2013 were searched for the diagnosis of intramural
leiomyoma in the second trimester ultrasonographic screening, past medical
history, demographics, pregnancy follow up, and pregnancy outcomes of pregnant
women. In the data analyses, 112 singleton pregnant women with intramural
leiomyoma were included in the study group and 168 singleton pregnant women
without leiomyoma were included in the control group. RESULTS: The presence of
pregnancy associated leiomyoma was found to be a risk factor for abortion (odds
ratio (OR):12.6, 95% confidence interval (CI) 2.5-63.6) hospitalization for pain
(OR: 19.6, 95% CI 5.8-66.5), premature rupture of mem- branes (OR: 6.7, 95% CI
1.4-32.4), oligohydramniosis (OR: 5.3, 95% CI 1.4-20.0), preterm birth (OR: 4.7,
95% CI 1.9-11.6), and breech presentation and other abnormal presentations (OR:
9.7, 95% CI 2.8-34.2) and neonatal intensive care need (OR: 3.0, 95% CI 1.2-7.5).
No correlation with the rate of intrauterine growth restriction, intrauterine
fetal death, placenta previa, abruption of placenta, and cesarean section was
found. CONCLUSIONS: Pregnancy associated intramural leiomyoma is a risk factor
for some perinatal complications and these results may be useful for prenatal
counseling.
PMID- 29944236
TI - Immunohistochemical expression of hormonal receptors, collagen, elastin, and
proteoglycans in genuine urinary incontinence.
AB - PURPOSE: To study the expression of hormonal receptors, collagen, elastin,
proteoglycans, and VIP in the vaginal wall of women with stress urinary
incontinence (SUI). MATERIALS AND METHODS: Fifty-eight specimens of the anterior
vaginal wall (28 women with SUI) were processed by Ventana immunostaining method.
RESULTS: Both groups were compatible for age, BMI, and obstetric history.
Positive ER-alpha and ER-beta immunoreaction was observed in 46.4% and 3.6% of
SUI (43.3% and 33.3% of controls) (p < 0.05), respectively, and PR immunoreaction
in 39.3% of SUI (46.7% of controls). Collagen I and III immunoreaction was
observed in 28,6% and 21.4% of SUI (30.% and 36.7% of controls), respectively,
and elastin, decorin, and fibromodulin immunoreaction in 10.7%, 10.7%, and 10.7%
of SUI (50%, 33.3%, 33,.3% of controls) (p < 0.05), respectively. VIP
immunoreaction was observed in 7.1% of SUI (36.7% of controls). CONCLUSION:
Imunoexpression of ER-P, elastin, decorin, fibromodulin, and VIP was
significantly lower in SUI than controls, showing that the ER-beta dependent re
modeling of the extracellular matrix of vaginal tissues is the main mechanism of
SUI.
PMID- 29944237
TI - The assessment of maternal and umbilical cord homocysteine levels in obese
pregnant women.
AB - PURPOSE: The aim of this study was to compare the maternal plasma and umbilical
cord blood homocysteine levels in obese and non-obese pregnant women. MATERIALS
AND METHODS: One hundred-ten term pregnant women, who completed their 3711,
gestational weeks and were not in active labor, were enrolled in the study. While
41 out of them were obese (BMI >= 30 kg/m(2)), 69 were non-obese (BMI < 30
kg/m(2)). The maternal plasma and umbilical cord homocysteine levels and
umbilical cord pH values were compared between the groups. The statistical
analyses were performed using t-test, Mann Whitney test, and Chi-square test. Ap
< 0.05 value was set as statistically significant. RESULTS: The mean of age was
higher in obese group in borderline significance (26.8 +/- 5.4 vs. 28.8 +/- 5.
l,p = 0.049). The mean of gestational weeks, birthweight, the mode of delivery,
and umbilical cord pH values were similar between the groups (p > 0.05). The
maternal plasma homocysteine levels [median (interquartile range); 7.6 (4.1) vs.
7.1 (4.9)] and umbilical cord homocysteine values were not statistically
different [8.6 (4.2) vs. 8.8 (4.5)] between the groups (p > 0.05). CONCLUSION:
The maternal and umbilical cord blood homocysteine levels are not different in
obese and non-obese pregnant women.
PMID- 29944238
TI - Three-dimensional transperineal ultrasound: is there a correlation among age,
weight, delivery mode, and a change in the pelvic floor architecture in Korean
premenopausal women?
AB - PURPOSE: The purpose of this study was to evaluate the morphological
characteristics and related factors of changes to the female pelvic floor
architecture during rest and the Valslva maneuver using three-dimensional (3D)
transperineal ultrasonography (TPUS) in parous women. MATERIALS AND METHODS: One
hundred thirty-five premenopausal parous women (aged 29-50 years) were evaluated.
The pelvic floor structures were measured during rest and during the Valsalva
maneuver using 3D TPUS. RESULTS: The delivery mode was an im- portant affecting
factor in determining the change of contractility of pelvic floor architecture.
The factors of age and weight were asso- ciated with changes in the anus.
CONCLUSION: The delivery mode might be a meaningful factor in the change of
contractility of pelvic floor architecture. These measurements provide a baseline
upon which further investigations in a larger cohort of subjects can be compared,
to determine the range and change of the normal appearance of the specific pelvic
structures.
PMID- 29944239
TI - The role of hysteroscopy in unexplained infertility.
AB - PURPOSE OF INVESTIGATION: To evaluate pregnancy rate after diagnostic and
operative hysteroscopy in nulliparous patients with inter- tility of unknown
cause. MATERIALS AND METHODS: The authors conducted this study on 92 nulliparous
patients with unexplained infer- tility that underwent diagnostic hysteroscopy
which showed an uterine lesion (submucous fibroids, uterine septa, polyps,
synechias) and underwent operative hysteroscopy to remove the lesion between 2007
and 2011. Patients' data were retrospectively extrapolated from patient's charts,
then the patients were called to ask if they had pregnancies after hysteroscopic
surgery. RESULTS: The present study showed a significant increase in pregnancy
rate after hysteroscopic surgery (85% during the two years after the surgery).
The most common endocavitary lesions were endometrial polyps (21%), uterine septa
(25%), and submucous myomas (18%). CONCLUSIONS: Ac- cording to the present data,
hysteroscopic evaluation of nulliparous women with unexplained infertility could
be useful to detect lesions not diagnosed with other tests, and the treatment of
these endocavitary lesions plays an important role in the diagnostic and
therapeutic iter. The results show-a pregnancy rate of 85% in the patients
treated for endocavitary lesions, but 15% of the patients, despite a normal
uterine cavity, continue to have unexplained infertility and are classified as
idiopathic infertility.
PMID- 29944240
TI - Monitoring and treatment results of 88 HBsAg-positive pregnant women.
AB - Approximately 5% of all women in the world are HBsAg-positive. Chronic hepatitis
B is a problem in women of reproductive age. This paper assessed 88 HBsAg
positive pregnant women, of whom 11 began treatment during pregnancy and five
became pregnant while receiving treatment. The files of HBsAg-positive pregnant
women were reviewed between January 2010 and December 2013-retrospectively. From
these 88 pregnant women, 72 did not receive any treatment during their pregnancy,
11 began treatment during their pregnancy, and five became pregnant while
receiving treatment. Nine of these 11 pregnant women were given tenofovir
disoproxil fumarate and two of them lamivudine. Ten babies of the 11 mothers that
began treatment during their pregnancy were healthy, but one was lost due to
preterm birth. Of the five patients who became pregnant while receiving
treatment, the treatments of four women were discontinued and they were monitored
during their pregnancies because mild-moderate (less than stage 3) fibrosis was
found in their liver biopsy results. It is important to screen all pregnant women
for hepatitis B and to assess those found HBsAg-positive. It is possible to
protect both the mother and baby using appropriate approaches.
PMID- 29944241
TI - Clinical analysis of 95 cases with ovarian pregnancy.
AB - BACKGROUND: Ovarian pregnancy (OP) is a rare ectopic pregnancy, in which it is
very difficult to achieve preoperative diagnosis. Ovarian blood supply in OP
increases which will lead to intra-abdominal bleeding, hazarding women's lives.
Surgical exploration should be conducted once cases of OP are suspected.
OBJECTIVE: To investigate clinical characteristics, diagnosis, and therapy of OP.
MATERIALS AND METHODS: A retrospective study was conducted in 95 patients with OP
admitted to the present hospital from January 2005 to June 2014. RESULTS: OP
accounted for 1.79% of ectopic pregnancy over the same period, of which 68.4% had
a history of artificial abortion, 6.3% was treated with intrauterine
contraceptive device (IUD), 87.4% had abdominal pain, 84.2% had a history of
menopause, and 51.6% had vaginal bleeding. All patients had no preoperative
diagnosis and underwent laparoscopic wedge resection of ovary or lesionectomy and
were all were cured. CONCLUSION: Since the cause of OP is still unknown and it
has no typical clinical manifestations, the present authors adopt blood P-hCG
combined with B-ultrasound to improve the preoperative diagnosis. They prefer
laparoscopic wedge resection of ovary or lesionectomy, which induce higher rate
of intrauterine pregnancy and lower rates of ectopic pregnancy and infertility in
re-pregnancy after surgery.
PMID- 29944242
TI - Effects of estradiol injection on outcome of in-vitro fertilization: a
randomized, double-blind, placebo controlled trial.
AB - PURPOSE: To evaluate the effects of estradiol (E2) supplementation on pregnancy
outcome in patients with unexplained infertility undergoing in vitro
fertilization (IVF). MATERIALS AND METHODS: A total of 100 women with unexplained
infertility and candidates for IVF, were included in this study and were randomly
assigned to receive E2 supplementation or placebo during the luteal phase. The E2
serum levels in the hCG administration day and third and seventh day after ovum
retrieval were measured in control group. The rate of pregnancy was also
quantified and compared between the two study groups. RESULTS: There was no
significant difference between two study groups regarding baseline
characteristics. E2 level decreased significantly in third (1765.34 +/- 680.09; p
< 0.001) and seventh (1459.66 +/- 593.80; p < 0.001) days after ovum retrieval
(2411.16 +/- 713.52). The authors found that the serum level of E2 was
significantly lower in those who received E2 supplementation at day 3 (p < 0.001)
and 7 (p<0.001). However the pregnancy rate was not significantly different
between two study groups (p = 0.849). In the same way, there was no significant
difference between two study groups regarding the number of retrieved oocytes (p
= 0.563) and number of MII oocytes (p = 0.103). CONCLUSIONS: E2 supplementation
during the luteal phase in patients with unexplained infertility undergoing IVF,
is associated with decreased serum levels of E2 after hCG injection. However the
fertility outcome was not affected by E2 supplementation.
PMID- 29944243
TI - Using the LigaSure vessel sealing device in the large uterus at laparoscopic
hysterectomy.
AB - OBJECTIVE: To compare intraoperative hemorrhage and other operative parameters
between patients with large and small weighted uterus who underwent laparoscopic
hysterectomy (LH). MATERIALS AND METHODS: Forty-six patients intending to have LH
were divided into two groups according to uterine weight (group 1 > 300 grams vs.
group 2 < 299 grams). Intraoperative blood loss, operating time, periopera- tive
complications, and duration of hospitalization were compared. RESULTS:
Intraoperative blood loss was significantly higher in the large uterus group
(group 1); 350 (227-454) ml vs. 250 (182-320) ml (p < 0.001). However, it was not
significantly different between the groups in the laparoscopy step. Mean
operating time was 90 (77-103) minutes and 80 (62-98) minutes in groups 1 and 2,
respectively (p < 0.001) revealing ten-minute delay in group 1. Similarly, this
was also not significantly different in the laparoscopy step. No significant
differences were found between two groups; in terms of hemoglobin concentration
decrease, major and minor complications, and hospitalization duration.
CONCLUSION: The authors conclude that LigaSure can be safely used for LH in
patients with a large uterus.
PMID- 29944244
TI - Analysis of the reason of abnormal uterine bleeding induced by copper corrosion
of IUD Cu.
AB - OBJECTIVES: This study aimed to analyze relationship of the copper corrosion of
copper intrauterine device (TCu220 IUD) and abnormal uterine bleeding. MATERIALS
AND METHODS: Sixty-four patients of abnormal uterine bleeding (too much blood
volume, shorten cycle, lengthen period or irregular vaginal bleeding) and 72
cases of normal menstrual cycle and quantity in the present hospital, which were
removed of IUD due to non-medical reasons, were enrolled, and 36 regular
menstruation cases without placing IUD were selected as control group, in which
had assessed in vitro copper ion release of TCu220 IUD and content of copper ions
and VEGF in endometrial tissue of each group of women. RESULTS: Daily Cu I UD
copper dissolution quantities of abnormal uterine bleeding women was
significantly higher than that of regular menstruation women (p < 0.05). Copper
ion content and the expression of VEGF in endometrial tissue of abnormal uterine
bleeding women was significantly higher than that of regular menstruation women
endometrial tissue (p < 0.05), and the endometrial VEGF expression had a positive
correlation with copper ion concentration in endometrial tissue. CONCLUSION: High
dissolution quantity of Cu IUD may lead to increase of copper ion content in
endometrial tissue and may cause VEGF secretion in the endometrium, and then the
occurrence of abnormal uterine bleeding.
PMID- 29944245
TI - Bulky fibroid and pregnancy: myomectomy is possible during pregnancy.
AB - When bulky fibroids are discovered during pregnancy, they can become acutely
complicated. The question of their resection thus arises. The authors report a
case of a woman who was diagnosed at eight weeks' gestation by ultrasound and
then by MRI, with a uterine fibroma measuring 22x12x15 cm.
PMID- 29944246
TI - A case of a 42-year-old patient with anomalous origin of the left main coronary
artery from the pulmonary artery who delivered three times with no complications:
presentation, diagnosis, and review.
AB - An anomalous origin of the left coronary artery (LCA) from the pulmonary artery
or Bland-White-Garland (BWG) syndrome is a rare congenital cardiac anomaly, which
is unusual to survive to adulthood if left uncorrected. The authors report an
unusual case of a multiparity patient who delivered several times without any
complications presenting at the age of 42 years with recurrent dyspnea on
exertion in which echocardiographic findings of diastolic flow near the origin of
the pulmonary valve were suggestive of anomalous origin of the LCA. A CT
angiography confirmed that the left main coronary artery arises from the
undersurface of the pulmonary flow close :o its origin and gives rise to a left
anterior descending (LAD) and left circumflex arteries.
PMID- 29944247
TI - Interstitial ectopic pregnancy after salpingectomy due to previous tubal
pregnancy - a case report.
AB - Ectopic pregnancy is the development of the embryo outside the uterine cavity. In
recent years an increase in the incidence of ectopic pregnancies has been
observed. It is mainly related to the increased number of IVF procedures. The
most frequent localization is the ampulla of the fallopian tube. In cases of
intramural or cornual ectopic pregnancies, many patients have a history of
ectopic pregnancy on the same side or underwent partial salpingectomy in the
past. Treatment of such pregnancies involves laparotomy and removal of the uterus
or comu of the uterus. This case concerns a patient operated because of
intramural pregnancy. She had a salpingectomy in the past because of tubal
ectopic pregnancy on the same side. This case shows that even after removal of
the fallopian tube there is still a risk of ectopic pregnancy in the intramural
part of this tube.
PMID- 29944248
TI - Asymptomatic isthmico-cervical uterine perforation with IUD - our experience and
literature review.
AB - PURPOSE: The study aim was to report an unusual case of a misplaced IUD in
isthmico-cervical region causing partial uterine perforation and discuss
literature data regarding such a condition. CASE REPORT: A 50-year-old women was
referred to the present institution for IUD extraction. She was diagnosed with
spontaneously misplaced IUD located in isthmico-cervical region of the uterus
causing partial perforation. The time of dislocation was unknown, as she was
completely asymptomatic for ten years after IUD application. More-over, she had
no risk factors for device misplacement. The removal of IUD was uneventful.
CONCLUSION: Isthmico-cervical misplacement of IUD, although rare, can occur at
any time and can be asymptomatic. Thus, women with IUD should be annually checked
up in order to prevent possible IUD complications.
PMID- 29944249
TI - Successful transvaginal aspiration of interstitial pregnancy after failed
methotrexate treatment.
AB - Interstitial pregnancy is an uncommon condition that is challenging, not only in
making an accurate diagnosis, but also in the choice of treatment. Systemic
methotrexate (MTX) treatment has been favored to prevent scarring of the uterus.
Nevertheless, surgery is generally indicated when this treatment fails.
Transvaginal aspiration of the gestational tissue has been proposed as an
alternative to surgery. The authors present a case of interstitial pregnancy in
which the patient failed to respond to multidose MTX treatment and was
successfully treated with transvaginal sonography-guided transvaginal aspiration
of the gestational tissue, thereby bypassing the risk associated with undergoing
major surgery. Transvaginal aspiration of conceptive tissue may be a novel
treatment for patients with unruptured interstitial pregnancy.
PMID- 29944250
TI - P450 oxidoreductase deficiency with maternal virilization during pregnancy.
AB - PURPOSE: The authors report on a rare case of maternal virilization during
pregnancy caused by autosomal recessive P450 oxidore- ductase (POR) deficiency.
MATERIALS AND METHODS: A 24-year-old primigravida developed a deepening voice and
hirsutism in the second trimester. Prenatal ultrasonography failed to detect any
fetal abnormality and fetal growth was normal. POR deficiency was suspected, but
the mother declined fetal genetic testing. A female neonate was delivered by
cesarean section at 41 weeks' gestation. RESULTS: The neonate had skeletal
abnormalities. Mutational analysis of the POR gene demonstrated homozygosity for
c.1370 G>A and p.R457H in the patient and heterozygosity in her parents. POR
deficiency was confirmed in the neonate. CONCLUSION: POR deficiency should be
suspected in cases of maternal virilization. Maternal urinary estriol, fetal
magnetic resonance imaging, and parental genetic testing should be performed.
Parental consent for fetal genetic testing should be sought to ensure prompt
diagnosis and early treatment.
PMID- 29944251
TI - Growing teratoma syndrome after ovarian inmature teratoma: a case report and
review of the literature.
AB - Growing teratoma syndrome is an uncommon complication of malignant germ cell
cancer, characterised by the development of large tumours during or after
chemotherapy, despite normalisation of tumour marker levels and metastasis, which
contain only mature teratoma. Given its low incidence, little is data available.
The authors present the case of a 15-year-old girl with a growing teratoma and
the literature review outlines the current knowledge of its pathogenesis, common
sites, diagnosis, natural course, treatment, and prognosis.
PMID- 29944252
TI - Analysis on two postmenopausal women with clinical symptoms resulting from
completely encapsulated intrauterine device by fibrous tissue.
AB - OBJECTIVES: To report two cases of retained intrauterine device (IUD)
encapusulated by fibrous tissues. CASES: Two cases of post-menopausal women had a
history of using IUD for over 30 years with clinical symptoms resulting from
completely encapsulated intrauterine device by fibrous tissue and the IUDs were
successfully removed through hysteroscopic and open surgery. CONCLUSIONS: IUD
could be severely encapsulated by fibrous tissue. The removal is possible with a
good understanding of the pathogenetic condition and a skilled operation under
hysteroscopy.
PMID- 29944253
TI - Large pedunculated angiomyofibroblastoma of the vulva with concomitant anemia: a
case report and mini review of the literature.
AB - Angiomyofibroblastoma is a rare myxoid tumor and is often seen in vulvar and
vaginal area. Patients usually present with a mass on the vulva or labium majus
at the premenopausal ages. The lesions are usually between 0.5 cm and ten cm.
Lesions have quite cellularity with regular borders under the microscope. Lesions
contain numerous veins and bulging stromal cells. Treatment of
angiomyofibroblastoma is simple surgical resection. Angiomyofibroblastoma should
be differentiated from the other vulvar neoplasms, which need radical surgical
treatment, especially from the aggressive angiomyxoma. Hereby, the authors aimed
to report a premenopausal women presented with vulvar mass and accompanying
anemia. She was diagnosed with angiomyofibroblastoma.
PMID- 29944254
TI - Reading Cosmographia: Peter Apian's Book- Instrument Hybrid and the Rise of the
Mathematical Amateur in the Sixteenth Century.
AB - The incorporation of paper instruments, also known as volvelles, into
astronomical and cosmographical texts is a well-known facet of sixteenth-century
printing. However, the impact that these instruments had on the reading public
has yet to be determined. This paper argues that the inclusion of paper
instruments in Peter Apian's Cosmographia transforms the text into a book
instrument hybrid. The instruments and accompanying text in Cosmographia enabled
readers to make their own measurements and calculations of both the heavens and
the earth. Through the experience of manipulating the instruments, the readers
became participants in sixteenth century mathematical culture, and thus
mathematical amateurs. I conclude that the presence of these mathematical
amateurs contributed to a much broader social base for the cultural shift towards
an empirical understanding of nature from 1500 to 1700.
PMID- 29944255
TI - The "Subtile Aereal Spirit of Fountains": Mineral Waters and the History of
Pneumatic Chemistry.
AB - The standard history of pneumatic chemistry is dominated by a landmark
discoverers-type narrative stretching from Robert Boyle, through Stephen Hales,
Joseph Black, and Joseph Priestley, to Antoine Lavoisier. This article challenges
this view by demonstrating the importance of the study of mineral waters - and
their "aerial component" - to the evolution of pneumatic chemistry, from around
van Helmont to the period before Black (1640s-1750s). Among key figures examined
are Joan Baptista van Helmont, Johann Joachim Becher, Robert Boyle, Friedrich
Hoffmann, and William Brownrigg.
PMID- 29944256
TI - Situating Kant's Pre-Critical Monadology: Leibnizian Ubeity, Monadic Activity,
and Idealist Unity.
AB - This essay examines the relationship between monads and space in Kant's early
precritical work, with special attention devoted to the question of ubeity, a
Scholastic doctrine that Leibniz describes as "ways of being somewhere." By
focusing attention on this concept, evidence will be put forward that supports
the claim, held by various scholars, that the monad-space relationship in Kant is
closer to Leibniz' original conception than the hypotheses typically offered by
the later Leibniz-Wolff school. In addition, Kant's monadology, in conjunction
with God's role, also helps to shed light on further aspects of his system that
are broadly Leibnizian, such as monadic activity and the unity of space.
PMID- 29944257
TI - Behind the headlines.
PMID- 29944258
TI - Unravelling the rebate riddle.
PMID- 29944259
TI - Working together: Peer support and occupational health.
PMID- 29944260
TI - Protecting little passengers.
PMID- 29944261
TI - Clinical update: Fever and rash in children.
PMID- 29944262
TI - Born to move: The importance of early physical activity and interaction.
AB - The Born to Move' project was initiated in response to health visitor concerns
that babies with increasingly sedentary lives were achieving their developmental
milestones later. Anecdotal evidence suggested that increasing numbers of
children were starting school before achieving the expected developmental levels
locally. The aim was to maximise the impact of health visitors in Kent, to enable
parents and carers to have a greater understanding of the importance of their
vital role in encouraging child development. Consistent promotion of key
messages, including the value of awake tummy time in infants and of interactive
play was achieved through multi-agency workshops for all health visiting and
children centre teams. Parents were also supported by a leaflet given by health
visitors at new birth visits, posters in all children's centres and access to a
specifically designed free smartphone app. The intervention was initially
introduced in one district. Measurable outcomes were obtained through collation
of existing one year review data. The number of babies who had crawled in the
first year increased from 30 per cent (baseline data), to 94 per cent a year
after the project started. A report to commissioners led to extension of the
project across Kent using the 'train the trainer' approach.
PMID- 29944263
TI - Innovation from the inside: Collaborating for school readiness.
AB - This paper will critically reflect on a service evaluation project that was
undertaken within Sussex Community NHS Foundation Trust in 2014/15. The project
sought to provide a new way of working that supported health visitors (HVs) and
school nurses (SNs) in developing effective collaborative and partnership working
practices in order to meet the health needs and improve the health outcomes of
children aged four to five years in preparation and readiness for school. HVs and
SNs are well placed to work with families and provide the early interventions and
health support required to support school readiness, e.g. behaviour, sleep,
eating and continence advice. Historically, within Susssex Community NHS
Foundation Trust, this public health approach has been taken on by the SN
service. However, problems were identified locally with this model due to several
factors including reduced staffing and confusion regarding transition of care
from HVs to SNs. In response, a new way of working was considered locally to
ensure the best possible service for families.
PMID- 29944265
TI - The human touch.
PMID- 29944264
TI - Last word with Suzanne Perry.
PMID- 29944266
TI - Good will hunting?.
PMID- 29944268
TI - Leading by example.
PMID- 29944267
TI - A Powerful Message.
PMID- 29944269
TI - How to enhance practice in a DIGITAL WORLD.
PMID- 29944270
TI - Act without delay.
PMID- 29944271
TI - Not adding up.
PMID- 29944272
TI - School nurses shall shine.
PMID- 29944273
TI - Another point of view.
PMID- 29944274
TI - Positive parenting.
PMID- 29944275
TI - Domestic abuse on your doorstep?.
PMID- 29944276
TI - Safety first.
PMID- 29944277
TI - ?
PMID- 29944278
TI - [Surgery of abdominal wall hernias in 2018 : an update of current practices].
AB - Abdominal wall hernias remain common problem that affect a large proportion of
the population from various ages. The management as well as the referral to
surgeons can be oriented with guidelines. One of the aims of this article is
identification of emergencies compared to eligible cases allowing watchful
waiting strategy in the setting of the three most common abdominal wall hernias.
The aim is to provide to the general practitioner an update and simple tools for
the current management.
PMID- 29944279
TI - [How to manage patients with a suspicion of gallstone migration into the common
bile duct ?]
AB - Symptomatic cholelithiasis associated with modified liver and pancreas function
tests should raise the suspicion of a gallstone migration into the common bile
duct (CBD). CBD evaluation is mainly done by endoscopic ultrasound or magnetic
resonance cholangio-pancreatography. CBD stone retrieval is performed by
endoscopic retrograde cholangio-pancreatography (ERCP). Patients at low-risk of
CBD stone should be treated by cholecystectomy without further investigation,
whereas high-risk patients should undergo CBD clearance before cholecystectomy.
For intermediate-risk patients, we recommend initial cholecystectomy with
intraoperative cholangiogram, followed if necessary by postoperative ERCP.
PMID- 29944280
TI - [Appendix tumours and their management].
AB - An appendix tumour is found every 100 appendectomies. It can also be incidental
discovery during a routine radiological examination and presents as a mucocele of
the appendix. Appendix tumours are of varied histological type, and include
mainly neuroendocrine tumours as well as epithelial tumours. The latter, when
they secrete mucin, can give rise to peritoneal pseudomyxoma, a particular form
of carcinosis harbouring serious complications. The management of appendix
tumours responds to specific recommendations and, in advanced cases, requires the
expertise of a university centre specialized in digestive oncology. The role of
the primary care practitioner lies in the diagnosis and referral of patients with
appendix tumours.
PMID- 29944281
TI - [Screening for anal cancer : is it the same as for cervical cancer ?]
AB - Anal dysplasia is usually caused by HPV infection and can lead to squamous anal
cancer. The purpose of this article is to describe the classification of these
precursor lesions but above all to identify the groups of patients at risk and to
clarify the screening and follow-up that must be initiated.
PMID- 29944282
TI - [Can the management and pronostic of pancreatic adenocarcinoma be improved ?]
AB - Pancreatic cancer is the 10th leading cause of death worldwide. It is a very
lethal and aggressive tumor, with a 5-year overall survival rate under 5 % for
confirmed ductal adenocarcinoma. Even though many genes have been identified as
possible treatment targets, surgery remains the only curative treatment. Imaging
is essential to the initial workup and is mostly based on CT-scan and MRI
studies. Resectability is based on the absence of distant metastases and arterial
vasculature infiltration. 3D imaging reconstruction could add precision to the
surgical evaluation. Many phase II non randomized studies have shown that neo
adjuvant chemotherapy had a positive effect on pancreatic cancer. Nevertheless
this approach is only reserved for cases with locally advanced tumors.
PMID- 29944283
TI - [Can surgery treat type 2 diabetes ? Yes, according to international companies].
AB - Type 2 diabetes (DM2) and obesity are chronic diseases that often coexist with
considerable morbidity and mortality. Approximately 85 % of all DM2 patients have
a body mass index (BMI) ranking them as overweight (BMI 25-29,9 kg/m2) or obese
(BMI > 30 kg/m2). Metabolic surgery is the only treatment for diabetes that
results in long-term remission in 23 to 60 % of patients in the office depending
on the preoperative duration of diabetes and the severity of the disease. This
review presents evidence for the use of metabolic surgery (CM) as a primary
treatment for DM2, potential mechanisms of its effects, and recommendations for
its use in expanded patient populations.
PMID- 29944284
TI - ?
PMID- 29944286
TI - ?
PMID- 29944285
TI - ?
PMID- 29944287
TI - ?
PMID- 29944289
TI - ?
PMID- 29944288
TI - ?
PMID- 29944290
TI - ?
PMID- 29944291
TI - ?
PMID- 29944292
TI - [Opioid consumption from 1985 to 2015 : The situation in Switzerland, with an
international comparison].
AB - In North America the massive increase in opioid prescriptions for chronic non
cancer pain has been a major health issue for several years. In Switzerland, the
situation is less well known. This article aims to present the evolution of the
Swiss consumption and replace it in a European and international context using
the International Narcotics Control Board database. Between 1985 and 2015, the
Swiss opioid consumption raised from 18 to 421 mg/person/year, making Switzerland
the 7th largest opioid consumer per capita in the world. This increase could be
due to more adequate pain management or liberalized opioid prescription for
indications unsupported by the current evidence. Given these elements, further
research is needed, yet increased caution is recommended when prescribing opioid
drugs.
PMID- 29944293
TI - [Opioids prescription in the vulnerable populations : the children and the
elderly. Practical guidelines].
AB - Pain management in ambulatory care regularly requires the prescription of
opioids. These drugs allow adequate analgesia achievement in many patients, but
inefficiency and/or intolerable side effects may limit their use. Factors related
to physiological particularities, comorbidities and comedication, as well as
difficulties related to drug intake and pain assessment, make children and the
elderly more vulnerable to variability in opioid response and problems of safety
and efficacy profile. The purpose of this article is to remain the specificities
of these two populations and to propose recommendations for the good use of
opioids for ambulatory care.
PMID- 29944294
TI - [Acute pain management in opioid-maintained patients].
AB - Treatment of acute nociceptive pain in patients with opioid substitution therapy
(OST) is an actual topic. The clinical features of this population, as pain
sensibility, and the pharmacological features of OST, require an individualized
care which must be adjusted to the patient's pain and the OST used. This article
offers a summary of the main possible pharmacological strategies by highlighting
the features of pain in these patients and removing the barriers to an effective
management. Generally, the OST is kept and a multimodal analgesia is added
according to the intensity of the pain. Multimodal analgesia includes non
pharmacological measures, non opioid drugs and/or opioid drugs which must be
chosen according to the OST. Collaboration between different health professionals
provides an effective management of pain in order to protect this vulnerable
population from the negative health consequences of an insufficiently relieved
pain.
PMID- 29944295
TI - [Pain and osteoarthritis].
AB - Osteoarthritis is one of the principal reasons for chronic pain worldwide. With
the increase of life span, sedentary lifestyle and obesity, its socioeconomic
impact is on the rise. The origin of osteoarthritis pain is heterogeneous and
related to structural changes of all intra-and para-articular components.
Optimization of biomechanics constitutes a principal pillar of therapeutic
strategies. Although disease-modifying concepts are the main goal, symptomatic
therapies may bring temporary relief. Identification of a neuropathic component
of pain is important to implement the optimal pharmacotherapy. Based on today's
knowledge, therapy evolves towards a multimodal approach, which should be
implemented early on.
PMID- 29944296
TI - [Pain, sex and neuroinflammation : toward gender bias?]
AB - While in clinical research epidemiological data indicate a higher prevalence of
chronic pain in women, preclinical research has long focused on male animal
models. Recently, in the study of neuropathic pain, it was found that mechanisms
responsible for pain behavior after a peripheral nerve injury in male differed
from the ones in female. At a time when gender equality is being claimed, science
is reviewing its copy and has to find the sex differences that could lead to new
and appropriate therapeutic targets.
PMID- 29944297
TI - [Pain management in adult medico-surgical wards : practical guidelines].
AB - Guidelines for pain management in the medical and surgical departments of the
Geneva University Hospitals (GUH) have been systematically developed using a
multidisciplinary approach. These guidelines are aimed towards improving
healthcare quality. We point to the ways the pain network of the GUH has elected
to deal with the ever-increasing progression of concepts regarding pain
management. This is of importance at a time when the risks related to the
patients' transitions between the different departments, to the specificities of
the clinical practices, and to the need for personalized care have never been so
high.
PMID- 29944298
TI - [Capgras delusion and Alzheimer disease].
AB - Capgras delusion is classified with the misidentification syndromes. In dementia
it associates cognitive deficiency of memory and facial recognition
(prosopoagnosia) with delirious idea of substitution by a double. The first
reported case in the paper describes the important affective and comportmental
reactions due to the identification of a double perceived as an imposter,
affecting both the suffering person and his family. Rarely, as reported in the
second case, misrecognition concerns the person itself (autoprosopagnosia) who
can have the illusion to be in front of a twin brother (" auto-Capgras "). We
discuss data from the literature concerning prevalence, results of cerebral
imaging and functional prognosis associated with this curious syndrome.
PMID- 29944299
TI - ?
PMID- 29944301
TI - ?
PMID- 29944300
TI - ?
PMID- 29944302
TI - ?
PMID- 29944303
TI - ?
PMID- 29944304
TI - ?
PMID- 29944305
TI - Work of the NHS England Youth Forum and its effect on health services.
AB - AIM: To examine the role of members of the NHS England Youth Forum (NHSEYF) and
the strategies used to influence health service provision for children and young
people. METHOD: An evaluative mixed-methods study was commissioned by NHS England
and undertaken by the University of Hertfordshire between July 2015 and September
2016. Data collection comprised activity logs, a form of questionnaire, and semi
structured interviews. FINDINGS: The analysis of the activity logs revealed that
the young people were undertaking a wide range of activities across England.
Seven themes emerged from the interviews: the young people; motivation;
commitment; community (the local area as well as a community spirit); knowledge
experts; youth workers; and funding. In summary, the members of the NHSEYF were
committed to their role and their work was having a positive effect on health
service provision. CONCLUSION: The NHSEYF has developed rapidly and successfully.
It is enabling the voice of young people to be heard.
PMID- 29944306
TI - Intervertebral disc herniation: prevalence and association with clinical
diagnosis.
AB - Background: Low back pain is one of the common health problems encountered in
life with intervertebral disc herniation being a common cause of its occurrence.
Magnetic resonance imaging has emerged the gold standard for diagnosing a
herniated disc. Aims and Objective: To assess the frequency and pattern of
occurrence of disc herniation as well as evaluate the association of disc
herniation on magnetic resonance imaging with clinical symptoms. Method: A total
of 120 adult patients who came for magnetic resonance imaging scan of the
lumbosacral spine for a period of 1year in the department of Radiology University
of Port-Harcourt Teaching Hospital. The end plates of 600 lumbar interspaces were
graded for type, size and site of lumbar disc herniation. Results: The age
distribution of patients was from 18-80 years; mean age was 51.0.
PMID- 29944307
TI - Malaria parasitaemia among febrile under-five children at Nnamdi Azikiwe
University Teaching Hospital, Nnewi, South-East, Nigeria.
AB - Background: Malaria is an infectious disease caused by Plasmodium and transmitted
by the bite of an infected female Anopheles mosquito. It continues to be a global
challenge with about half of the world's population being at risk of the disease
and under-5 children being the most vulnerable. Aims and Obejectives: To
determine the prevalence of malaria parasitaemia and some associated symptoms
among febrile under-five children presenting at Nnamdi Azikiwe University
Teaching Hospital Nnewi, Nigeria. Materials and Methods: A total of 200 children
under the age of five years were recruited for the study. Data on socio
demographic characteristics and symptoms were collected through interviewer
administered questionnaire. They were physically examine and blood sample was
collected from each of them. The Blood smear was Giemsa stained and examined
microscopically for malaria parasite. Result: There were 118 males and 82
females, giving a male: female ratio of 1.44:1. Their ages ranged from 3-59
months and the average age was 27+17.49 months. Those in the age range of 12-23
months and 24-35 months constitute the highest number (23%) each. Forty-seven
(23.5%) came from the rural area while 153(76.5%) came from the urban area.
Average number of days the subjects had fever before presentation were 3.78+1.95
days with a range of 1-30 0 days. Body temperature ranged from 35.9-40.4 C with
average of 37.7+0.8oC. Forty (20%) were positive to microscopy. Those in the age
range of 47-59 months have the highest prevalence of malaria. Parasite density
ranged from 40-136,000/MUL with a mean of 18,687.2+3360/MUL. All the children who
are positive by microcopy had Plasmodium falciparium as the specie causing
malaria. Conclusion: Malaria parasitaemia among these under-5 children is 20%.
PMID- 29944308
TI - Monthly sulphadoxine-pyrimethamine combination versus daily proguanil for malaria
chemoprophylaxis in sickle cell disease: a randomized controlled study at the Jos
University Teaching Hospital.
AB - Background: Malaria carries a high case fatality among patients with sickle cell
disease. In Jos University Teaching Hospital, at the time of this study, the use
of Proguanil was the acceptable mode of chemoprophylaxis for preventing malaria
in these patients. Intermittent Preventive Treatment (IPT) with Sulphadoxine
Pyrimethamine [SP] has shown great potential for reducing the prevalence of
malaria and anaemia among pregnant women, infants and travellers. We hypothesised
that monthly SP was superior to daily Proguanil in reducing malaria parasitaemia,
clinical malaria attacks and sickle cell crises in such patients. Objective: To
assess the efficacy and affordability of monthly SP versus daily Proguanil for
malaria chemoprophylaxis in patients attending Sickle Cell Clinic at Jos
University Teaching Hospital, Plateau State, Nigeria. Methods: One hundred and
fifty four patients [114 children and 40 adults] with Sickle Cell Disease in
their steady state were randomized to monthly SP or daily Proguanil for malaria
chemoprophylaxis. Active detection of malaria parasite in the peripheral blood
and packed cell volumes were done at each monthly visit to the clinic over a
period of three months. The primary outcome measure was the proportion of
patients with malaria parasite in the peripheral blood at the end of 3 months.
The secondary outcome measures included episodes of clinical malaria attacks,
frequency and type of sickle cell crises and adverse effects of the medication.
Results: Ninety four percent [72/77] of patients in the SP group and 91% [70/77]
in the Proguanil group respectively completed three months of follow up. SP
reduced the prevalence of malaria parasitaemia by 25% [(14%) 10/72] compared to
6.4% [(30%) 21/70] in the proguanil group. [X2 54; p = 0.01]. Seventeen percent
[12/72] of the patients receiving monthly SP had malaria attacks compared to 57%
[40/70] on prophylaxis with Proguanil. [X2 =25; p< 0.0003]. Thirty three percent
[24/72] of the patients receiving SP had at least an episode of bone pain crises
compared to 69% [48/70] of the patients receiving Proguanil. [X2 =17.6;
p<0.0001]. SP was 8 times cheaper than Proguanil. Conclusion: Monthly
chemoprophylaxis with SP was more efficacious than daily Proguanil in reducing
the prevalence of asymptomatic malaria parasitaemia, clinical malaria attack and
sickle cell crises in patients with sickle cell disease. SP was 8 times cheaper
than Proguanil. No significant side effect was recorded in both groups. The
current practice of routinely prescribing daily Proguanil to SCD patients for
malaria chemoprophylaxis needs to be reviewed.
PMID- 29944309
TI - Prevalence and determinants of glucose intolerance among HIV/AIDS patients in
north-central Nigeria.
AB - Background: The advent of potent antiviral drugs has revolutionalised the
clinical course of HIV / AIDS resulting in increased survival and improved
quality of life. Metabolic derangements in HIV infected patients are becoming
more common probably due to this increased survival from the use of HAART. There
is limited data on the occurrence of glucose intolerance among HIV patients in
Nigeria. Objective: To determine the prevalence of glucose intolerance and
associated risk factors in HIV/AIDS patients. Results: Of the 584 patients
studied, 384 (130 males and 251 females) with mean+/-SD age of 38+/-15 years were
HAARTtreated; while 200 (61 males and 139 females) with mean+/-SD age of 33+/-17
years were HAART-naive. Overall, the prevalence of GI was 40.4% (IFG) 19.5%, IGT
11.5% and DM 9.4%. The prevalence of IFG (27.1%) and DM (11.2%) in HAART -
treated patients were observed and those in HAART-naive patients were (IFG
5.0%,DM 6.0%), p<0.005. IGT was more prevalent in HAART-naive than in HAART
treated patients (19.5%, and 7.3% respectively), p<0.05. The proportions of
patients with GI were higher in overweight and obese HAART-treated patients with
moderate CD4 cell count (200-500 x106 cell/L); while in the HAART-naive patients,
GI was more prevalent in underweight subjects with CD4 cell count (<200 x 106
cell/L). The Determinants of GI were age, increasing BMI, low CD4 cell count,
metabolic syndrome and HAART treatment duration. The independent predictors of
glucose intolerance in HIV / AIDS patients were low CD4 cell count and prolonged
HAART treatment duration. Conclusion: The prevalence of GI among HIV/AIDS
patients in North-Central Nigeria is high. Treatment with HAART and low CD4 cell
count are strong determinants of glucose intolerance in our HIV / AIDS patients.
Regular screening for glucose intolerance among our HIV / AIDS patients is
recommended.
PMID- 29944310
TI - Mentorship in orthopaedic and trauma residency training programme in Nigeria: the
residents' perspective.
AB - Background: Mentorship is important in residency training as it is necessary for
personal and professional development of the resident trainees. Objectives: This
study documents mentorship in orthopaedic residency training programme in Nigeria
by assessing the awareness of orthopaedic residents on the role of a mentor,
willingness to be mentored and their perceived reasons for the possible lack of
mentors/ participation of senior colleagues in a mentorship programme. Method:
This was a descriptive cross sectional study of 37 orthopaedic residents
attending a revision course of the Faculty of Orthopaedics, National Postgraduate
Medical College of Nigeria. Self-administered structured questionnaires were used
to collect data. Data obtained was analyzed using SPSS version 21.0. Results: The
mean age of the respondent was 34.7 +/- 4.7 years. The Male: Female ratio was
19:1. The average number of years already spent in the residency programme by the
respondents was 2.8 +/- 0.9 years. Only 27% of residents had participated in a
mentorship programme since they began residency programme but only half were
still being mentored at the time of the study. Sixty-five percent reported no
formal mentorship programme in their institutions. However, 73% of the
respondents would want a formal mentorship programme in their institution. Ninety
percent of the respondents desired to be mentored. Conclusion: Most residents are
willing to be mentored. Consultants and trainers should ensure that the trainees
are mentored.
PMID- 29944311
TI - Complications following nasotracheal intubation using cuffed polyvinyl chloride
tube: a prospective cross sectional study.
AB - Background: To examine the complications following nasotracheal intubation by
documenting the nasal traumas observed with the use of untreated cuffed polyvinyl
chloride tube in unprepared nostrils. Methods: Patients who had maxillofacial
surgeries under general anesthesia, muscle relaxation and nasotracheal intubation
were included in the study. Nasotracheal intubation was carried out after
induction of anesthesia was effected with intravenous propofol and suxamethonium
by an Anesthetist using well lubricated cuffed polyvinyl chloride tube. Sizes
6.0, 6.5 and 7.0mm were inserted in females while sizes 7.0 and 7.5mm were
inserted in males. Occasionally, the natural curve of the tube guides it through
the cords without the aid of Magill forceps. Anterior rhinoscopy was performed by
otolaryngologist 24 hours after surgery. Results were subjected to statistical
analysis. Results: Sixty four patients were included in the study. They were
between the ages of 21 and 63 years (mean 33.2 +/- 14.1 years); they were 39
males and 25 females. The most frequently used nasotracheal tube (NT) was size
7.0mm internal diameter. Epistaxis was noticed in 52 (81.2%) patients. There were
no statistically significant differences in the incidence of epistaxis observed
in males and females, and also between right and left nostrils. A total of 46.8%
of nasal trauma were inferior turbinate trauma involving the inferior medial
aspect. Conclusion: The use of untreated cuffed polyvinyl chloride tube for
nasotracheal intubation in unprepared nostrils is associated with a high
incidence of epistaxis and nasal trauma.
PMID- 29944312
TI - Clinical practitioners' knowledge of ionizing radiation doses in diagnostic
radiology examinations in Calabar.
AB - Background: Observation has shown a preponderance of irrelevant, unjustified and
perhaps unnecessary radiological requests in the study area. The consequences of
this on the patients' doses and population collective dose may be dire.
Objective: To assess Clinicians/Referrers' knowledge of radiation doses of
patients undergoing radiological examinations. Methodology: A prospective, non
experimental, cross-sectional survey of clinicians (except radiologists) in
various hospitals in Calabar metropolis, Cross River State, Nigeria, was
conducted. A pretested and validated questionnaire was designed to extract
responses on rating of effective doses for commonly requested imaging
examinations, using the value for the posterior-anterior (PA) chest x-ray as
reference. Questions on radiosensitivity of different organs, imaging modalities
that use ionizing radiation and considerations for the choice of ionizing
radiation (IR) based examinations were included. Participants were also asked for
their preferred methods of filling any knowledge gap on IR issues. Responses were
presented in simple percentages. Results: A total of 104 respondents, made up of
63.5% males and 36.5% females participated in the study. At least 70% and 42% of
the respondents, respectively, were aware that Ultrasound and Magnetic Resonance
Imaging were not IR based modalities. About 67.3% of the respondents did not know
the doses of commonly requested radiological examinations. This result was not
dependent on clinicians' demography. A total of 61.5% of the respondents referred
patients for IR examinations even when the result was unlikely to alter their
diagnosis or treatment; but to reassure the patient (98.8% ), meet expectations
of patients (35%) or to give the patient the feeling of being taken seriously
(75%). Conclusion: Participating Clinicians in this study have showed poor
knowledge of radiation doses of commonly requested radiological examinations.
Most participants suggested improvement of their knowledge of radiation doses
through continuous medical education and by the provision of referral guidelines.
PMID- 29944313
TI - FEV1, FVC, FEV1 /FVVC as predictors of rhinitis among saw mill workers in north
central Nigeria.
AB - Background: Rhinitis is one of the commonest occupational related respiratory
disorders that is only restricted to the upper airway but can involve the lower
respiratory tract with considerable airflow limitation, this study was conducted
assess the ventilator function of persons exposed to saw dust with rhinitis
symptoms. Methods: This is a cross sectional study carried out among 200 randomly
selected saw mill workers and 200 healthy staff of Jos University Teaching
Hospital staff in Jos metropolis from September to November 2008. Data on
sociodemographic variables, symptoms of rhinitis, etc was obtained using a
modified semi structured British medical research council questionnaire while
respiratory function data was measured using a spirometry. Result: A total of 400
responds comprising of 200 saw mill workers and 200 controls participated in this
study. Based on diagnostic criteria. 43% of the subjects fit into diagnosis of
rhinitis, 33% had asthma symptoms and 24 % did not fit into any category compared
to none of < 5% of the control group. The ventilatory function based on FEV1,
FVC, FEV1/FVC ratio and PEFR showed a significant decline when matched with
controls and predicted value, suggesting an airflow limitation among the rhinitis
group. Conclusion: Rhinitis associated with wood dust exposure is not restricted
to airway but involves the entire respiratory tract with airflow limitation as
one of its consequences.
PMID- 29944314
TI - An evaluation of intra-operative and post-operative blood loss in total knee
arthroplasty at the National Orthopaedic Hospital, Lagos.
AB - Background: Total knee replacement is a rewarding and reliable procedure,
producing a lasting relief to severe knee pains. However, significant blood loss
usually in the post-operative period may be a challenge, necessitating prompt
restoration of circulating blood volume to minimize morbidity and mortality. The
aim of this study was to evaluate blood loss after total knee replacement.
Patients and Methods: A prospective study of blood loss after Total Knee
Arthroplasty in 53 patients in the National Orthopaedic Hospital, Lagos.
Consecutive patients with established indications, presenting for total knee
arthroplasty were recruited into the study after obtaining their consent.
Results: The mean intra-operative blood loss was 342.4 mls, with a range of 50 -
1500 mls. The mean post-operative blood loss and total blood loss were 603.6 mls
and 940.3 mls respectively, showing a strong positive correlation (r = 0.884, p <
0.01). The average pre-operative and post-operative haemoglobin concentration
were 12.5 +/- 1.2 g/dl and 9.8 +/- 0.9 g/dl, respectively. The mean haemoglobin
loss was 2.6 +/- 1.2 g/dl (r = 0.46, p < 0.001). Conclusion: Post-operative blood
loss as measured by suction drainage, is a good predictor of total blood loss,
showing a strong and positive correlation.
PMID- 29944315
TI - Effect of education and training on patient referral by public primary health
care workers in Mushin Local Government Area to State General Hospitals.
AB - Background: Poor referral linkages had been noted and documented by various
researchers on the health care delivery system in Nigeria. This study is designed
to find out the situation of referral practices and make recommendations on how
to improve the situation. Materials and Methods: A quasi-experimental study was
carried out to determine the effect of health education and training on the
Knowledge, attitude and practices of patient referral by primary health care
workers in Mushin and Surulere Local Government Areas of Lagos State of Nigeria.
A total sample of 170 primary health care workers was involved in the study: 85
in each of the Local Government Areas. The study involved three stages, the pre
intervention, the intervention phase, and a post intervention phase of the study.
Results: Analysis of the responses of the two groups showed that there was no
statistically significant difference in the responses in the areas concerning
their attitude towards, and knowledge of patient referral at the pre-intervention
phase.In the post-intervention phase the differences in the responses between the
two groups in the area of practice of patient referral were statistically
significant. In the control group 18.8% of the workers used the two-way referral
form in the pre-intervention phase. This rose to 27.1% in the post intervention
phase. In the experimental group, 17.5% used the two-way referral form in the pre
intervention phase, and this rose to 69.4% in the post intervention phase.
Conclusion: The conclusion was that education and training on patient referral
could improve the patient referral activities of primary health care workers.
PMID- 29944316
TI - Prevalence of sickle cell gene among apparently healthy under-two south-east
Nigerian children: what is the role of parental premarital counselling and socio
demographic characteristics? A pilot study.
PMID- 29944317
TI - Dentine hypersensitivity: real or imagined.
PMID- 29944318
TI - Percutanous vertebroplasty for vertebral compression fracture in geriatric
patients; a report of two cases.
PMID- 29944319
TI - Anomalous renal artery is potential cause of resistant hypertension in a 53 year
old patient: case report.
AB - Background: Drug-resistant hypertension can be attributable to secondary
hypertension and other causes. Anomalous renal artery is uncommon but can be a
potential cause of resistant hypertension. Case Report: We highlight the
challenges in management of resistant hypertension and describe its unusual
association with renal artery anomaly in 53 years old man who was referred to our
nephrology clinic from a peripheral general hospital on account of poorly
controlled hypertension. At presentation, BP was severely elevated at 208/100mmHg
but no remarkable findings in the rest of the examination. Several investigations
done including abdominal ultrasound scan and Computerised Tomography (CT) Renal
angiogram revealed a Left anomalous renal artery. Patient declined all suggested
urologic interventions and he was then managed conservatively. Conclusion: We
found that anomalous renal arteries can be a potential cause of resistant
hypertension. We therefore recommend ultrasound scan of the abdomen as a
screening modality due to its being non-invasive.
PMID- 29944320
TI - Histopathology practice and training in Nigeria - a model.
AB - Objectives: Contemporary histopathology practice and training in Nigeria have
been plagued by the fundamental issue of inadequate exposure to surgical
pathology material by both trainees and trainers. This paper critically examines
the factors that affect the discipline and profers practical solutions to aid its
advancement. Materials and Method: This review is based on the authors experience
and observations of histopathology practice in Nigeria. Results: The Nigerian
health sector is plagued by many ills including poor funding, weak policies,
dilapidated structures, disgruntled and frustrated practitioners, amongst others
and pathologists are not immune to all these. In recent times, there has been a
proliferation of accredited training centres as well as medical graduates
interested in the specialty of histopathology. The busiest histopathology
laboratories in the country ascession between 2200 and 5500 surgical samples
yearly. Thus there is inadequate exposure by histopathologists and trainee
pathologists to surgical materials with the attendant consequences. Many centres
still rely principally on routine haematoxylineosin stains. There are no
nationally agreed standard reporting formats for most diseases. Conclusion: The
development of a deanery or regional system of accredited histopathology
laboratories may form the fulcrum for improving the overall quality of
histopathological services and training in Nigeria. This will help develop local
expertise and ensure adequate exposure to teaching aids and surgical materials.
We hope that the proffered solutions will help encourage local pathologists to
continue and increase their efforts to raise the profession up to enviable
heights.
PMID- 29944334
TI - Bacterial Inhibition and Osteoblast Adhesion on Ti Alloy Surfaces Modified by
Poly(PEGMA- r-Phosmer) Coating.
AB - We have synthesized and immobilized PEGMA500-Phosmer to Ti6Al4V surfaces by a
simple procedure to reduce bacteria-associated infection without degrading the
cell response. Adhered bacteria coverage was lessened to 1% on polymer-coated
surfaces when exposed to Escherichia coli, Staphylococcus epidermidis, and
Streptococcus mutans. Moreover, PEGMA500-Phosmer and homoPhosmer coatings
presented better responses to MC3T3-E1 preosteoblast cells when compared with the
results for PEGMA2000-Phosmer-coated and raw Ti alloy surfaces. The behavior of
balancing bacterial inhibition and cell attraction of the PEGMA500-Phosmer
coating was explained by the grafted phosphate groups, with an appropriate PEG
brush length facilitating greater levels of calcium deposition and further
fibronectin adsorption when compared with that of the raw Ti alloy surface.
PMID- 29944335
TI - Stereoisomers of Schisandrin B Are Potent ATP Competitive GSK-3beta Inhibitors
with Neuroprotective Effects against Alzheimer's Disease: Stereochemistry and
Biological Activity.
AB - Glycogen synthase kinase-3beta (GSK-3beta) is a key enzyme in
hyperphosphorylation of tau proteins and is a promising therapeutic target in
Alzheimer's disease (AD). Here, we reported, for the first time, that the
stereoisomers of Schisandrin B (Sch B), (+)-1, (-)-1, (+)-2, and (-)-2, were
potent GSK-3beta inhibitors. They were demonstrated to selectively target GSK
3beta in an orthosteric binding mode, with IC50 values of 340, 290, 80, and 70
nM, respectively. Further study showed that these stereoisomers can significantly
increase the expression of p-GSK-3beta (Ser9) and decrease the expressions of p
GSK-3beta (Tyr216) and p-GSK-3beta (Tyr279). Finally, these compounds can
alleviate the cell injury induced by Abeta, and the cognitive disorders in AD
mice, especially (+)-2 and (-)-2. Collectively, the stereoisomers of Sch B,
especially (+)-2 and (-)-2, were found to be potential selective ATP-competitive
GSK-3beta inhibitors, which further affected their anti-AD effects. These
promising findings explained the biological target of Sch B in AD, and bring a
new understanding in the stereochemistry and bioactivities of Sch B.
PMID- 29944336
TI - Structural Basis of Small Molecule Targetability of Monomeric Tau Protein.
AB - The therapeutic targeting of intrinsically disordered proteins (IDPs) by small
molecules has been a challenge due to their heterogeneous conformational
ensembles. A potential therapeutic strategy to alleviate the aggregation of IDPs
is to maintain them in their native monomeric state by small molecule binding.
This study investigates the structural basis of small molecule druggability of
native monomeric Tau whose aggregation is linked to the onset of Tauopathies such
as Alzheimer's disease. Initially, two available monomeric conformational
ensembles of a shorter Tau construct K18 (also termed Tau4RD) were analyzed which
revealed striking structural differences between the two ensembles, while similar
number of hot spots and small molecule binding sites were identified on monomeric
Tau ensembles as on tertiary folded proteins of similar size. Remarkably, some
critical fibril forming sequence regions of Tau (V306-K311, V275-K280)
participated in hot spot formation with higher frequency compared to other
regions. As an example of small molecule binding to monomeric Tau, it was shown
that methylene blue (MB) bound to monomeric K18 and full-length Tau selectively
with high affinity (Kd = 125.8 nM and 86.6 nM, respectively) with binding modes
involving Cys291 and Cys322, previously reported to be oxidized in the presence
of MB. Overall, our results provide structure-based evidence that Tau can be a
viable drug target for small molecules and indicate that specific small molecules
may be able to bind to monomeric Tau and influence the way in which the protein
interacts among itself and with other proteins.
PMID- 29944337
TI - Self-Assembly-Assisted Facile Synthesis of MoS2-Based Hybrid Tubular
Nanostructures for Efficient Bifunctional Electrocatalysis.
AB - In this work, MoS2-based hybrid tubular nanostructures are facilely synthesized
via a self-assembly-assisted process and evaluated as a bifunctional
electrocatalyst for hydrogen evolution reactions (HERs) and oxygen reduction
reactions (ORRs). By simply mixing the reactants under ambient conditions,
(NH4)2MoS4/polydopamine (PDA) hybrid nanospheres are formed. The protonated
dopamine is linked to tetrahedral [MoS4]2- via weak N-H...S and O-H...S
interactions, causing the PDA nanospheres merging together and forming nanorods
under stirring-induced shear force. Moreover, the oxidative polymerization of
dopamine proceeds on the surface of the nanorods, whereas it is prohibited inside
the nanorods owing to lack of oxygen, leading to outward diffusion of dopamine
and hence cavitation. After annealing, the tubular morphology is perfectly
retained, while ultrafine MoS2 monolayers are formed due to the confinement of
the framework. Benefiting from these unique structural features, the MoS2/C
hybrid nanotubes possess abundant active sites and high surface area, as well as
boost electronic and ionic transport, remarkably enhancing their electrocatalytic
activities. The onset and half-wave potentials are 0.91 and 0.82 V, respectively,
for ORR, close to those of Pt/C. Moreover, low onset potential and small Tafel
slope are also observed for HER, demonstrating the potential of the hybrid
nanotubes as a promising non-noble metal bifunctional electrocatalyst.
PMID- 29944338
TI - De Novo-Designed alpha-Helical Barrels as Receptors for Small Molecules.
AB - We describe de novo-designed alpha-helical barrels (alphaHBs) that bind and
discriminate between lipophilic biologically active molecules. alphaHBs have five
or more alpha-helices arranged around central hydrophobic channels the diameters
of which scale with oligomer state. We show that pentameric, hexameric, and
heptameric alphaHBs bind the environmentally sensitive dye 1,6-diphenylhexatriene
(DPH) in the micromolar range and fluoresce. Displacement of the dye is used to
report the binding of nonfluorescent molecules: palmitic acid and retinol bind to
all three alphaHBs with submicromolar inhibitor constants; farnesol binds the
hexamer and heptamer; but beta-carotene binds only the heptamer. A co-crystal
structure of the hexamer with farnesol reveals oriented binding in the center of
the hydrophobic channel. Charged side chains engineered into the lumen of the
heptamer facilitate binding of polar ligands: a glutamate variant binds a
cationic variant of DPH, and introducing lysine allows binding of the
biosynthetically important farnesol diphosphate.
PMID- 29944339
TI - Clinical Trials and Therapeutic Rationale for Drug Repurposing in Schizophrenia.
AB - There is a paucity of efficacious novel drugs to address high rates of treatment
resistance and refractory symptoms in schizophrenia. The identification of novel
therapeutic indications for approved drugs-drug repurposing-has the potential to
expedite clinical trials and reduce the costly risk of failure which currently
limits central nervous system drug discovery efforts. In the present Review we
discuss the historical role of drug repurposing in schizophrenia drug discovery
and review the main classes of repurposing candidates currently in clinical
trials for schizophrenia in terms of their therapeutic rationale, mechanisms of
action, and preliminary results from clinical trials. Subsequently we outline the
challenges and limitations which face the clinical repurposing pipeline and how
novel technologies might serve to address these.
PMID- 29944340
TI - Sequence Specific Modeling of E. coli Cell-Free Protein Synthesis.
AB - Cell-free protein synthesis (CFPS) is a widely used research tool in systems and
synthetic biology. However, if CFPS is to become a mainstream technology for
applications such as point of care manufacturing, we must understand the
performance limits and costs of these systems. Toward this question, we used
sequence specific constraint based modeling to evaluate the performance of E.
coli cell-free protein synthesis. A core E. coli metabolic network, describing
glycolysis, the pentose phosphate pathway, energy metabolism, amino acid
biosynthesis, and degradation was augmented with sequence specific descriptions
of transcription and translation and effective models of promoter function. Model
parameters were largely taken from literature; thus the constraint based approach
coupled the transcription and translation of the protein product, and the
regulation of gene expression, with the availability of metabolic resources using
only a limited number of adjustable model parameters. We tested this approach by
simulating the expression of two model proteins: chloramphenicol
acetyltransferase and dual emission green fluorescent protein, for which we have
data sets; we then expanded the simulations to a range of additional proteins.
Protein expression simulations were consistent with measurements for a variety of
cases. The constraint based simulations confirmed that oxidative phosphorylation
was active in the CAT cell-free extract, as without it there was no feasible
solution within the experimental constraints of the system. We then compared the
metabolism of theoretically optimal and experimentally constrained CFPS
reactions, and developed parameter free correlations which could be used to
estimate productivity as a function of carbon number and promoter type. Lastly,
global sensitivity analysis identified the key metabolic processes that
controlled CFPS productivity and energy efficiency. In summary, sequence specific
constraint based modeling of CFPS offered a novel means to a priori estimate the
performance of a cell-free system, using only a limited number of adjustable
parameters. While we modeled the production of a single protein in this study,
the approach could easily be extended to multiprotein synthetic circuits, RNA
circuits, or the cell-free production of small molecule products.
PMID- 29944341
TI - FT-IR Hyperspectral Imaging and Artificial Neural Network Analysis for
Identification of Pathogenic Bacteria.
AB - Identification of microorganisms by Fourier transform infrared (FT-IR)
spectroscopy is known as a promising alternative to conventional identification
techniques in clinical, food, and environmental microbiology. In this study we
demonstrate the application of FT-IR hyperspectral imaging for rapid, objective,
and cost-effective diagnosis of pathogenic bacteria. The proposed method involves
a relatively short cultivation step under standardized conditions, transfer of
the microbial material onto suitable IR windows by a replica method, FT-IR
hyperspectral imaging measurements, and image segmentation by machine learning
classifiers, a hierarchy of specifically optimized artificial neural networks
(ANN). For cultivation, aliquots of the initial microbial cell suspension were
diluted to guarantee single-colony growth on solid agar plates. After a short
incubation period when microbial microcolonies achieved diameters between 50 and
300 MUm, microcolony imprints were produced by using a specifically developed
stamping device which allowed spatially accurate transfer of the microcolonies'
upper cell layers onto IR-transparent CaF2 windows. Dry microcolony imprints were
subsequently characterized using a mid-IR microspectroscopic imaging system
equipped with a focal plane array (FPA) detector. Spectral data analysis involved
preprocessing, quality tests, and the application of supervised modular ANN
classifiers for hyperspectral image segmentation. The resulting easily
interpretable segmentation maps suggest a taxonomic resolution below the species
level.
PMID- 29944342
TI - Laser Ablation as a Versatile Tool To Mimic Polyethylene Terephthalate
Nanoplastic Pollutants: Characterization and Toxicology Assessment.
AB - The presence of micro- and nanoplastics in the marine environment is raising
strong concerns since they can possibly have a negative impact on human health.
In particular, the lack of appropriate methodologies to collect the nanoplastics
from water systems imposes the use of engineered model nanoparticles to explore
their interactions with biological systems, with results not easily correlated
with the real case conditions. In this work, we propose a reliable top-down
approach based on laser ablation of polymers to form polyethylene terephthalate
(PET) nanoplastics, which mimic real environmental nanopollutants, unlike
synthetic samples obtained by colloidal chemistry. PET nanoparticles were
carefully characterized in terms of chemical/physical properties and stability in
different media. The nanoplastics have a ca. 100 nm average dimension, with
significant size and shape heterogeneity, and they present weak acid groups on
their surface, similarly to photodegraded PET plastics. Despite no toxic effects
emerging by in vitro studies on human Caco-2 intestinal epithelial cells, the
formed nanoplastics were largely internalized in endolysosomes, showing
intracellular biopersistence and long-term stability in a simulated lysosomal
environment. Interestingly, when tested on a model of intestinal epithelium, nano
PET showed high propensity to cross the gut barrier, with unpredictable long-term
effects on health and potential transport of dispersed chemicals mediated by the
nanopollutants.
PMID- 29944343
TI - Adsorption of PFOA at the Air-Water Interface during Transport in Unsaturated
Porous Media.
AB - Miscible-displacement experiments are conducted with perfluorooctanoic acid
(PFOA) to determine the contribution of adsorption at the air-water interface to
retention during transport in water-unsaturated porous media. Column experiments
were conducted with two sands of different diameter at different PFOA input
concentrations, water saturations, and pore-water velocities to evaluate the
impact of system variables on retardation. The breakthrough curves for
unsaturated conditions exhibited greater retardation than those obtained for
saturated conditions, demonstrating the significant impact of air-water
interfacial adsorption on PFOA retention. Retardation was greater for lower water
saturations and smaller grain diameter, consistent with the impact of system
conditions on the magnitude of air-water interfacial area in porous media.
Retardation was greater for lower input concentrations of PFOA for a given water
saturation, consistent with the nonlinear nature of surfactant fluid-fluid
interfacial adsorption. Retardation factors predicted using independently
determined parameter values compared very well to the measured values. The
results showed that adsorption at the air-water interface is a significant source
of retention for PFOA, contributing approximately 50-75% of total retention, for
the test systems. The significant magnitude of air-water interfacial adsorption
measured in this work has ramifications for accurate determination of PFAS
migration potential in vadose zones.
PMID- 29944344
TI - Glucose-Responsive Peptide Coacervates with High Encapsulation Efficiency for
Controlled Release of Insulin.
AB - A new glucose-responsive insulin delivery system is fabricated using biomimetic
peptide coacervates derived from the Humboldt squid (Dosidicus Gigas) beak. Both
insulin and glucose oxidase are coencapsulated within coacervate microdroplets.
The glucose oxidase quickly responds to increasing glucose levels to generate a
local acidic environment, thereby rapidly triggering the dissociation of pH
sensitive coacervates to release the insulin cargo. The rate of insulin release
is dependent on the glucose level, increases under hyperglycemic conditions, and
decreases under normoglycemic conditions. This glucose responsiveness mimics
pancreatic beta-cell function by releasing insulin according to glucose levels.
PMID- 29944345
TI - Targeting the Unique Mechanism of Bacterial 1-Deoxy-d-xylulose-5-phosphate
Synthase.
AB - The bacterial metabolite 1-deoxy-d-xyulose 5-phosphate (DXP) is essential in
bacterial central metabolism feeding into isoprenoid, thiamin diphosphate (ThDP),
and pyridoxal phosphate de novo biosynthesis. Halting its production through the
inhibition of DXP synthase is an attractive strategy for the development of novel
antibiotics. Recent work has revealed that DXP synthase utilizes a unique random
sequential mechanism that requires formation of a ternary complex among pyruvate
derived C2alpha-lactylthiamin diphosphate (LThDP), d-glyceraldehyde 3-phosphate
(d-GAP), and enzyme, setting it apart from all other known ThDP-dependent
enzymes. Herein, we describe the development of bisubstrate inhibitors bearing an
acetylphosphonate (AP) pyruvate mimic and a distal negative charge mimicking the
phosphoryl group of d-GAP, designed to target the unique form of DXP synthase
that binds LThDP and d-GAP in a ternary complex. A d-phenylalanine-derived
triazole acetylphosphonate (d-PheTrAP) emerged as the most potent inhibitor in
this series, displaying slow, tight-binding inhibition with a Ki* of 90 +/- 10
nM, forward ( k1) and reverse ( k2) isomerization rates of 1.1 and 0.14 min-1,
respectively, and exquisite selectivity (>15000-fold) for DXP synthase over
mammalian pyruvate dehydrogenase. d-PheTrAP is the most potent, selective DXP
synthase inhibitor described to date and represents the first inhibitor class
designed specifically to exploit the unique E-LThDP-GAP ternary complex in ThDP
enzymology.
PMID- 29944346
TI - Impact of D1-V185 on the Water Molecules That Facilitate O2 Formation by the
Catalytic Mn4CaO5 Cluster in Photosystem II.
AB - The oxidations of the O2-evolving Mn4CaO5 cluster in Photosystem II are coupled
to the release of protons to the thylakoid lumen via one or more proton egress
pathways. These pathways are comprised of extensive networks of hydrogen-bonded
water molecules and amino acid side chains. The hydrophobic residue, D1-V185, is
adjacent to numerous water molecules in one of these pathways. The D1-V185N
mutation dramatically slows O-O bond formation. This impairment has been
attributed to a disruption of the hydrogen-bonded water molecules that are
crucial for proton egress or whose rearrangement is required for catalysis. In
this study, Fourier transform infrared spectroscopy was employed to characterize
the impact of the D1-V185N mutation on the carboxylate groups and water molecules
that form a network of hydrogen bonds in this putative proton egress pathway. By
analyzing carboxylate stretching modes, carbonyl stretching modes of hydrogen
bonded carboxylic acids, O-H stretching modes of hydrogen-bonded water molecules,
and D-O-D bending modes, we obtain evidence that the D1-V185N mutation perturbs
the extensive network of hydrogen bonds that extends from YZ to D1-D61 to a
greater extent than any mutation yet examined but does not alter the water
molecules that interact directly with D1-D61. The mutation also alters the
environments of the carboxylate groups whose p Ka values change in response to
the S1 to S2 and S2 to S3 transitions. Finally, the mutation alters the
environment of the water molecule whose bending mode vanishes during the S2 to S3
transition, consistent with assigning the Ca2+-bound W3 as the water molecule
that deprotonates and joins oxo bridge O5 during the S2 to S3 transition,
possibly as the second substrate water molecule for O2 formation.
PMID- 29944347
TI - Molecular Toxicity of Metal Oxide Nanoparticles in Danio rerio.
AB - Metal oxide nanoparticles can exert adverse effects on humans and aquatic
organisms; however, their toxic mechanisms are still unclear. We investigated the
toxic effects and mechanisms of copper oxide, zinc oxide, and nickel oxide
nanoparticles in Danio rerio using microarray analysis and the comet assay.
Copper oxide nanoparticles were more lethal than the other metal oxide
nanoparticles. Gene ontology analysis of genes that were differentially expressed
following exposure to all three metal oxide nanoparticles showed that the
nanoparticles mainly affected nucleic acid metabolism in the nucleus via
alterations in nucleic acid binding. KEGG analysis classified the differentially
expressed genes to the genotoxicity-related pathways "cell cycle", "Fanconi
anemia", "DNA replication", and "homologous recombination". The toxicity of metal
oxide nanoparticles may be related to impairments in DNA synthesis and repair, as
well as to increased production of reactive oxygen species.
PMID- 29944348
TI - Phase Behavior of Acetylated Cellulose Nanocrystals and Origins of the Cross
Hatch Birefringent Texture.
AB - Cellulose nanocrystals hydrolyzed by hydrochloric acid and esterified by acetic
acid produce acetylated cellulose nanocrystals (CNC-AA) with acetyl ester surface
functional groups. While much attention has been paid to understanding the phase
behavior (liquid crystal) of aqueous dispersions of sulfonated nanocrystals,
relatively few studies have focused on CNC-AA dispersions. CNC-AA dispersions
exhibit multiple phase regimes and markedly different phase behavior due to their
lower surface charge. At concentrations above 5.0 * 10-4%vol, a decrease in the
apparent diffusion coefficient indicates the onset of interparticle interactions
and a transition from the dilute regime. From 0.003 to 0.31%vol, biphasic
behavior is observed, consisting of a birefringent lower phase and disordered or
isotropic upper phase. Small-angle neutron scattering was used to measure the
growth of fractal structures with increasing concentration and indicates a two
dimensional assembly with short-range order in a plate-like assembled geometry.
Above 0.31%vol, the dispersion transitions exhibit a cross-hatch birefringent
texture, which is believed to exist as a fine-scale nematic that possesses frozen
in flow shear behavior, consistent with a glassy phase. This cross-hatch pattern
is maintained in dried films, where atomic force microscopy and scanning electron
microscopy reveal a layered sheet-like structure. Imaging also indicates that the
basic unit of CNC-AA microstructure in the film consists of 0.5-1.5 MUm scale
aligned nanorod domains, which agrees with neutron scattering and the dimensions
of each individual "hatch" in the birefringent texture observed by cross
polarized microscopy. The assembly of the nanorods into this layered structure
and the fine-scale nematic birefringent cross-hatch texture is of significant
fundamental interest, particularly since it differs greatly from cellulose
nanocrystals with other surface chemistry and offers potential opportunities in
other applications owing to the unique assembly.
PMID- 29944349
TI - Electron-Rich Metal Cations Enable Synthesis of High Molecular Weight, Linear
Functional Polyethylenes.
AB - Group 10 metal catalysts have shown much promise for the copolymerization of
nonpolar with polar alkenes to directly generate functional materials, but access
to high copolymer molecular weights nevertheless remains a key challenge toward
practical applications in this field. In the context of identifying new
strategies for molecular weight control, we report a series of highly polarized
P(V)-P(III) chelating ligands that manifest unique space filling and
electrostatic effects within the coordination sphere of single component Pd
polymerization catalysts and exert important influences on (co)polymer molecular
weights. Single component, cationic phosphonic diamide-phosphine (PDAP) Pd
catalysts are competent to generate linear, functional polyethylenes with Mw up
to ca. 2 * 105 g mol-1, significantly higher than prototypical catalysts in this
field, and with polar content up to ca. 9 mol %. Functional groups are positioned
by these catalysts almost exclusively along the main chain, not at chain ends or
ends of branches, which mimics the microstructures of commercial linear low
density polyethylenes. Spectroscopic, X-ray crystallographic, and computational
data indicate PDAP coordination to Pd manifests cationic yet electron-rich active
species, which may correlate to their complementary catalytic properties versus
privileged catalysts such as electrophilic alpha-diimine (Brookhart-type) or
neutral phosphine-sulfonato (Drent-type) complexes. Though steric blocking within
the catalyst coordination sphere has long been a reliable strategy for catalyst
molecular weight control, data from this study suggest electronic control should
be considered as a complementary concept less prone to suppression of comonomer
enchainment that can occur with highly sterically congested catalysts.
PMID- 29944350
TI - One-Pot Sequential Kinetic Profiling of a Highly Reactive Manganese Catalyst for
Ketone Hydroboration: Leveraging sigma-Bond Metathesis via Alkoxide Exchange
Steps.
AB - A comprehensive experimental and computational mechanistic study of the highly
enantioselective hydroboration of ketones catalyzed by a manganese(II) alkyl
boxmi pincer complex is reported. The catalyst operates at low catalyst loadings
(down to 0.01 mol %) under very mild conditions (typically -40 degrees C) and
facilitates the reduction of both aryl alkyl and dialkyl ketones with excellent
selectivity (up to >95%ee). Catalyst activation pathways were investigated,
demonstrating that a manganese(II) hydride and a manganese(II) alkoxide species
are part of the catalytic cycle and can be generated via sigma-bond metathesis of
the alkyl precursor with the borane or by alcoholysis. Extensive kinetic
experiments based on a "one-pot sequential kinetic profiling" approach under
various conditions in combination with kinetic simulations reveal that two
catalytic cycles are effective with this earth-abundant base metal catalyst: (i)
a minor MnH/borane-mediated insertion cycle, in which the subsequent, product
releasing metathesis step is rate determining ( k m = 0.076 s-1), giving a
background reaction, which is zeroth order in substrate concentrations, and (ii)
a major MnOR/borane-based alkoxide exchange process, leveraging the high-barrier
metathesis via the affiliation to an insertion step. The latter features non
integer reaction orders in both reagents due to a combination of an adduct
formation step ( k a = 2.12 M-1 s-1, k -a = 0.49 s-1) and a substrate insertion
step of comparable rates ( k ai = 3.74 M-1 s-1). The kinetic findings are
underpinned by high-level density functional theory calculations of the
mechanism, control experiments, and kinetic isotope effect/Hammett/Eyring
analysis in different concentration regimes. The study highlights the role of a
rigorous mechanistic understanding of homogeneous catalytic processes in 3d
metals for rational catalyst discovery and optimization.
PMID- 29944351
TI - Dynamic Geospatial Modeling of the Building Stock To Project Urban Energy Demand.
AB - In the United States, buildings account for more than 40% of total energy
consumption and the evolution of the urban form will impact the effectiveness of
strategies to reduce energy use and mitigate emissions. This paper presents a
broadly applicable approach for modeling future commercial, residential, and
industrial floorspace, thermal consumption (heating and cooling), and associated
GHG emissions at the tax assessor land parcel level. The approach accounts for
changing building standards and retrofitting, climate change, and trends in
housing and industry. We demonstrate the automated workflow for California and
project building stock, thermal energy consumption, and associated GHG emissions
out to 2050. Our results suggest that if buildings in California have long
lifespans, and minimal energy efficiency improvements compared to building codes
reflective of 2008, then the state will face a 20% or higher increase in thermal
energy consumption by 2050. Baseline annual GHG emissions associated with thermal
energy consumption in the modeled building stock in 2016 is 34% below 1990 levels
(110 Mt CO2eq/y). While the 2020 targets for the reduction of GHG emissions set
by the California Senate Bill 350 have already been met, none of our scenarios
achieve >80% reduction from 1990 levels by 2050, despite assuming an 86%
reduction in electricity carbon intensity in our "Low Carbon" scenario. The
results highlight the challenge California faces in meeting its new energy
efficiency targets unless the State's building stock undergoes timely and
strategic turnover, paired with deep retrofitting of existing buildings and
natural gas equipment.
PMID- 29944352
TI - Oxygen-Atom Vacancy Formation at Polyoxovanadate Clusters: Homogeneous Models for
Reducible Metal Oxides.
AB - We report the first example of oxygen-atom vacancy formation at the surface of a
polyoxometalate, highlighting the ability of a polyoxovanadate-alkoxide cluster,
[V6O7(OCH3)12]1-, to function as a homogeneous model for reducible metal oxides.
The removal of an oxide ion from [V6O7(OCH3)12]1- results in the formation of a
reactive vanadium(III) cation within the multimetallic framework. Generation of
[V6O6(OCH3)12]1- is confirmed by 1H NMR, infrared and electronic absorption
spectroscopies, as well as electrospray ionization mass spectrometry. The
consequences of oxygen atom removal on the electrochemical profile of the
assembly are assessed, revealing that stabilization of the reduced cluster is
achieved through delocalized electron density. The oxygen-atom vacancy permits
activation of O2, demonstrating the ability of polyoxovanadate-alkoxide clusters
to serve as both structural and functional models of reducible metal oxides.
PMID- 29944353
TI - Reactions of Neutral Scandium/Phosphorus Lewis Pairs with Small Molecules.
AB - Treating a scandium mixed alkyl/diaryloxide complex with phosphino-substituted
alcohols resulted in the formation of scandium mixed alkoxyl/diaryloxide
complexes Sc[OC(CH3)2CH2PR2][O-2,6- tBu2-C6H3]2[THF] (6, R = Ph; 8, R = tBu). The
reactivity of Sc-based Lewis pair complexes 6 and 8 toward a wide range of
substrates was investigated. A ligand substitution reaction occurred when complex
6 was treated with benzophenone. The reaction of complex 6 with sulfur afforded a
phosphane oxidative product. Complexes 6 and 8 also exhibited typical Sc/P
frustrated Lewis pair (FLP) reactivity. They added to the carbonyl group of
phenyl isocyanate to form seven-membered metallacycles. Complex 6 underwent
selective Sc/P 1,4-addition reactions with alpha,beta-unsaturated carbonyl
compounds to give the corresponding nine-membered metallacyclic products. The
reaction of 6 with 0.5 mol of dimethyl acetylenedicarboxylate led to the
formation of bicyclo[7.7.0]cetane-derived metallacycle 16 in a distinctive double
1,4-addition pattern. With benzil complex 6 underwent a 1,4-addition reaction to
afford a cis-enediolate which was coordinated to the Sc/P FLP through Sc-O and P
O bonds. Treatment of complex 6 with cyclopropyl phenyl ketone afforded the 10
membered metallaheterocycle 18, in which a scandium Lewis acid added to the
oxygen atom and the phosphine Lewis base attacked the cyclopropyl group with ring
opening. A ring-opening reaction also took place when epoxycyclohexane was
employed as a substrate. Complex 6 successfully cleaved the C-Br bond of benzyl
bromide to give zwitterionic complex 20 with newly formed Sc-Br and P-C bonds.
Scandium phosphazine complex 21 was generated by a Sc/P 1,1-addition to the
terminal nitrogen atom of (trimethylsilyl)diazomethane. Aided by the phosphorus
Lewis base, scandium Lewis acid was able to abstract chloride from (Ph3P)AuCl to
produce heterobimetallic Sc/Au complexes 22 and 23. Many complexes in this study
were characterized by single-crystal X-ray diffraction.
PMID- 29944355
TI - Experimental and Theoretical Studies on alpha-In2Se3 at High Pressure.
AB - alpha(R)-In2Se3 has been experimentally and theoretically studied under
compression at room temperature by means of X-ray diffraction and Raman
scattering measurements as well as by ab initio total-energy and lattice-dynamics
calculations. Our study has confirmed the alpha ( R3 m) -> beta' ( C2/ m) -> beta
( R3 m) sequence of pressure-induced phase transitions and has allowed us to
understand the mechanism of the monoclinic C2/ m to rhombohedral R3 m phase
transition. The monoclinic C2/ m phase enhances its symmetry gradually until a
complete transformation to the rhombohedral R3 m structure is attained above 10
12 GPa. The second-order character of this transition is the reason for the
discordance in previous measurements. The comparison of Raman measurements and
lattice-dynamics calculations has allowed us to tentatively assign most of the
Raman-active modes of the three phases. The comparison of experimental results
and simulations has helped to distinguish between the different phases of In2Se3
and resolve current controversies.
PMID- 29944354
TI - Morphology Optimization via Side Chain Engineering Enables All-Polymer Solar
Cells with Excellent Fill Factor and Stability.
AB - All-polymer solar cells (all-PSCs) composed of conjugated polymers as both donor
and acceptor components in bulk heterojunction photoactive layers have attracted
increasing attention. However, it is a big challenge to achieve optimal
morphology in polymer:polymer blends. In response, we report herein a new
strategy to adjust the nanoscale organization for all-PSCs. Specifically, side
chain engineering of the well-known naphthalene diimide (NDI)-based polymer N2200
is modulated by introducing a fraction of linear oligoethylene oxide (OE) side
chains to replace branched alkyl chains on the NDI units and by synthesizing a
series of NDI-based polymer acceptors NOE x, where x is the percentage of OE
chain substituted NDI units relative to total NDI units. Compared to the
reference polymer NOE0, OE-chain-containing polymer NOE10 offers a much higher
power conversion efficiency (PCE) of 8.1% with a record high fill factor (FF) of
0.75 in all-PSCs. Moreover, the NOE10-based all-PSC exhibits excellent long-term
and thermal stabilities with >97% of the initial PCE being maintained after 300 h
of aging at 65 degrees C. This work demonstrates an effective morphology
optimization strategy to achieve highly efficient and stable all-PSCs and shows
the excellent potential of NOE10 as an alternative to commercially available
acceptor polymers N2200.
PMID- 29944356
TI - Nucleotide-Resolution Genome-Wide Mapping of Oxidative DNA Damage by Click-Code
Seq.
AB - Single-nucleotide-resolution sequencing of DNA damage is required to decipher the
complex causal link between the identity and location of DNA adducts and their
biological impact. However, the low abundance and inability to specifically
amplify DNA damage hinders single-nucleotide mapping of adducts within whole
genomes. Despite the high biological relevance of guanine oxidation and seminal
recent advances in sequencing bulky adducts, single-nucleotide-resolution whole
genome mapping of oxidative damage is not yet realized. We coupled the
specificity of repair enzymes with the efficiency of a click DNA ligation
reaction to insert a biocompatible locator code, enabling high-throughput,
nucleotide-resolution sequencing of oxidative DNA damage in a genome. We
uncovered thousands of oxidation sites with distinct patterns related to
transcription, chromatin architecture, and chemical oxidation potential. Click
code-seq overcomes barriers to DNA damage sequencing and provides a new approach
for generating comprehensive, sequence-specific information about chemical
modification patterns in whole genomes.
PMID- 29944357
TI - Genetically Encoded Catalytic Hairpin Assembly for Sensitive RNA Imaging in Live
Cells.
AB - DNA and RNA nanotechnology has been used for the development of dynamic molecular
devices. In particular, programmable enzyme-free nucleic acid circuits, such as
catalytic hairpin assembly, have been demonstrated as useful tools for
bioanalysis and to scale up system complexity to an extent beyond current
cellular genetic circuits. However, the intracellular functions of most synthetic
nucleic acid circuits have been hindered by challenges in the biological delivery
and degradation. On the other hand, genetically encoded and transcribed RNA
circuits emerge as alternative powerful tools for long-term embedded cellular
analysis and regulation. Herein, we reported a genetically encoded RNA-based
catalytic hairpin assembly circuit for sensitive RNA imaging inside living cells.
The split version of Broccoli, a fluorogenic RNA aptamer, was used as the
reporter. One target RNA can catalytically trigger the fluorescence from tens-to
hundreds of Broccoli. As a result, target RNAs can be sensitively detected. We
have further engineered our circuit to allow easy programming to image various
target RNA sequences. This design principle opens the arena for developing a
large variety of genetically encoded RNA circuits for cellular applications.
PMID- 29944358
TI - Luminescence and Energy Transfer between Ce3+ and Pr3+ in BaY2Si3O10 under VUV
vis and X-ray Excitation.
AB - A detailed investigation on photoluminescence properties and energy transfer (ET)
dynamics of Ce3+, Pr3+-doped BaY2Si3O10 is provided along with the potential X
ray excited luminescence application. The luminescence properties of Pr3+ are
studied in VUV-UV-vis spectral range at low temperature, and the spectral
profiles of Pr3+3P0 and 1D2 emission lines are determined using time-resolved
emission spectra. Upon 230 nm excitation, the electron population from Pr3+ 4f5d
state to its 4f2 excited state is discussed in detail. As Pr3+ concentration
rises, Pr3+3P0 and 1D2 luminescence possess different concentration-related
properties. The incorporation of Ce3+ in the codoped sample produces the strong
Ce3+ luminescence under 230 nm excitation, which is the combined result of Pr3+
4f5d -> Ce3+ 5d ET and Ce3+ intrinsic excitation. On the other hand, the
increasingly strong ET of Ce3+ 5d -> Pr3+ 4f2 results in the decrease of Ce3+
emission intensity and the gradual deviation of Ce3+ luminescence decay from the
single exponential in the system. By employing the Inokuti-Hirayama model, the
dipole-dipole interaction is confirmed as the predominant multipolar effect in
controlling this ET process, and the value of C DA is determined to be 9.97 * 10
47 m6.s-1. Finally, the relatively low scintillation light yield of Ce3+-doped
BaY2Si3O10 material impedes its application potential in the scintillator field,
and the cosubstitution of Pr3+ results in the observable decline of scintillation
performance.
PMID- 29944359
TI - Controlled Tuning of the Properties in Optoelectronic Self-Sorted Gels.
AB - Multicomponent supramolecular gels have great potential for optoelectronics.
Ideally, we could control the self-assembly of multiple components across many
length scales, from the primary assembled structures to how these are arranged in
space. This would allow energy transfer between p-type and n-type fibers to be
controlled. Usually, a single network is formed and analyzed. It is not clear how
most networks could be modified, and certainly not how these might be
differentiated. Here, we address both of these issues. We show how the different
components in a multicomponent gel can be differentiated by small-angle neutron
scattering using contrast-matching experiments. The rate of self-assembly can be
used to vary the networks that are formed, leading directly to changes in the
efficiency of electron transfer. The assembly kinetics can therefore be used to
prepare different networks from the same primary building blocks and primary self
assembled structures. We expect that these advances will allow multicomponent
systems to become effective electronic materials.
PMID- 29944360
TI - Exploration of the Effects of gamma-Phosphate-Modified ATP Analogues on Histidine
Kinase Autophosphorylation.
AB - While two-component systems (TCSs), composed of a sensor histidine kinase (HK)
and a response regulator, are the main signaling pathways in bacteria, global TCS
activity remains poorly described. Here, we report the kinetic parameters of the
HK autophosphorylation reaction using previously uncharacterized gamma-phosphate
modified ATP analogues to further elucidate their utility as activity-based
probes for global TCS analysis. Given the increased stability of
thiophosphorylated histidine in comparison to that of the native phosphoryl
modification, which is attributed to the decreased electrophilicity of this
moiety, we anticipated that ATPgammaS may be turned over much more slowly by the
HKs. Surprisingly, we found this not to be the case, with the turnover numbers
decreasing <1 order of magnitude. Instead, we found that alkylation of the
thiophosphate had a much more dramatic effect on turnover and, in one case, the
binding affinity of this substrate analogue (BODIPY-FL-ATPgammaS).
PMID- 29944361
TI - At Long Last: Olefin Metathesis Macrocyclization at High Concentration.
AB - Macrocyclic lactones, ketones, and ethers can be obtained in the High
Concentration Ring-Closing Metathesis (HC-RCM) reaction in high yield and
selectivity at concentrations 40 to 380 times higher than those typically used by
organic chemists for similar macrocyclizations. The new method consists of using
tailored ruthenium catalysts together with applying vacuum to distill off the
macrocyclic product as it is formed by the metathetical backbiting of oligomers.
Unlike classical RCM, no large quantities of organic solvents are used, but
rather inexpensive nonvolatile diluents, such as natural or synthetic paraffin
oils. Moreover, use of a protecting atmosphere or a glovebox is not needed, as
the new catalysts are perfectly moisture and air stable. In addition, some other
cyclic compounds previously reported as unobtainable by RCM in neat conditions,
or in high dilutions even, can be formed with the help of the HC-RCM method.
PMID- 29944362
TI - Aggregation Behavior of Multiwalled Carbon Nanotube-Titanium Dioxide Nanohybrids:
Probing the Part-Whole Question.
AB - Multiwalled carbon nanotube-titanium dioxide (MWNT-TiO2) nanohybrids (NHs), a
promising support for electrocatalysts, have a high likelihood of environmental
release. Aggregation of these NHs may or may not be captured by the sum of their
component behavior, thus necessitating a systematic evaluation. This study probes
the "part-whole question" by systematically evaluating the role of TiO2 loading
(C:Ti molar ratios of 1:0.1, 1:0.05 and 1:0.033) on the aggregation behavior of
these NHs. Aggregation kinetics of these in-house synthesized (using a sol-gel
method) NHs and the components is investigated with time-resolved dynamic light
scattering in the presence of mono- and divalent cations and with and without
Suwannee River humic acid. A deviation in the aggregation behavior from classical
electrokinetic theory has been observed which indicates that the material
complexity has a strong influence in the observed behavior; hence other material
attributes (e.g., fractal dimension, surface roughness, charge heterogeneity,
etc.) should be carefully considered when studying such materials. The sum of the
aggregation behavior of the parts may not capture that of the whole (i.e., of the
NHs); aggregation depends on the TiO2 loading and also on the hybridization
process and the background aquatic chemistry.
PMID- 29944363
TI - Density Functional Theory under the Bubbles and Cube Numerical Framework.
AB - Density functional theory within the Kohn-Sham density functional theory (KS-DFT)
ansatz has been implemented into our bubbles and cube real-space molecular
electronic structure framework, where functions containing steep cusps in the
vicinity of the nuclei are expanded in atom-centered one-dimensional (1D)
numerical grids multiplied with spherical harmonics (bubbles). The remainder,
i.e., the cube, which is the cusp-free and smooth difference between the atomic
one-center contributions and the exact molecular function, is represented on a
three-dimensional (3D) equidistant grid by using a tractable number of grid
points. The implementation of the methods is demonstrated by performing 3D
numerical KS-DFT calculations on light atoms and small molecules. The accuracy is
assessed by comparing the obtained energies with the best available reference
energies.
PMID- 29944364
TI - Biological and Chemical Control of Sclerotinia sclerotiorum using Stachybotrys
levispora and Its Secondary Metabolite Griseofulvin.
AB - Sclerotinia sclerotiorum is responsible for the white mold of soybeans, and the
difficulty to control the disease in Brazil is causing million-dollar damages.
Stachybotrys levispora has shown activity against S. sclerotiorum. In our present
investigation, we analyzed the chemical basis of this inhibition. Eight compounds
were isolated, and using spectroscopic methods, we identified their structures as
the known substances 7-dechlorogriseofulvin, 7-dechlorodehydrogriseofulvin,
griseofulvin, dehydrogriseofulvin, 3,13-dihydroxy-5,9,11-trimethoxy-1
methylbenzophenone, griseophenone A, 13-hydroxy-3,5,9,11-tetramethoxy-1
methylbenzophenone, and 12-chloro-13-hydroxy-3,5,9,11-tetramethoxy-1
methylbenzophenone. Griseofulvin inhibited the mycelial growth of S. sclerotiorum
at 2 MUg mL-1. Thus, the antagonistic effect of S. levispora to S. sclerotiorum
may well be due to the presence of griseofulvins. Our results stimulate new work
on the biosynthesis of griseofulvins, to locate genes that encode key enzymes in
these routes and use them to increase the production of these compounds and thus
potentiate the fungicide effect of this fungus. S. levispora represents an agent
for biocontrol, and griseofulvin represents a fungicide to S. sclerotiorum.
PMID- 29944365
TI - Hapten-Grafted Programmed Probe as a Corecognition Element for a Competitive
Immunosensor to Detect Acetamiprid Residue in Agricultural Products.
AB - We have developed an effective competitive electrochemical immunosensor assay
based on hapten-grafted programmed probe (HGPP) as a corecognition element for
highly sensitive and selective detection of acetamiprid. Starting with the
synthesis of hapten, HGPP was prepared using carboxyl group in the hapten and
amino group in the 5' end of the programmed probe through covalent conjugation.
Acetamiprid present in samples competes with HGPP to bind with capture antibody
on the electrodes by specific recognition interaction. Methylene blue probe (MBP)
was used as the electrochemical redox probe to capture the hybridized HGPP on the
electrodes. The competitive reaction changes in accordance with the quantity of
the target acetamiprid in the sample, as the amounts of the hybridized HGPP and
the immobilized antibody are constant, i.e., the more acetamiprid samples are
added, the less MBP is combined on the electrodes. In the optimal conditions,
thus, biosensor output showed a linear relationship from 5 to 105 ng L-1 for the
acetamiprid assay with a detecting limit of 3.2 ng L-1. The biosensor was
successful in quantifying the amount of acetamiprid in spiked strawberry and
cabbage extracts. This competitive immunosensor assay represents a rapid and
sensitive technology for acetamiprid assay or other small molecule targets in
food.
PMID- 29944367
TI - Anharmonic Densities of States for Vibrationally Excited I-(H2O), (H2O)2, and I
(H2O)2.
AB - Monte Carlo sampling calculations were performed to determine the anharmonic sum
of states, Nanh( E), for I-(H2O), (H2O)2, and I-(H2O)2 versus internal energy up
to their dissociation energies. The anharmonic density of states, rhoanh( E), is
found from the energy derivative of Nanh( E). Analytic potential energy functions
are used for the calculations, consisting of TIP4P for H2O...H2O interactions and
an accurate two-body potential for the I-...H2O fit to quantum chemical
calculations. The extensive Monte Carlo samplings are computationally demanding,
and the use of computationally efficient potentials was essential for the
calculations. Particular emphasis is directed toward I-(H2O)2, and distributions
of its structures versus internal energy are consistent with experimental studies
of the temperature-dependent vibrational spectra. At their dissociation
thresholds, the anharmonic to harmonic density of states ratio, rhoanh( E)/rhoh(
E), is ~2, ~ 3, and ~260 for I-(H2O), (H2O)2, and I-(H2O)2, respectively. The
large ratio for I-(H2O)2 results from the I-(H2O)2 -> I-(H2O) + H2O dissociation
energy being more than 2 times larger than the (H2O)2 -> 2H2O dissociation
energy, giving rise to highly mobile H2O molecules near the I-(H2O)2 dissociation
threshold. This work illustrates the importance of treating anharmonicity
correctly in unimolecular rate constant calculations.
PMID- 29944368
TI - Mechanistic Insights into Stereospecific Bioactivity and Dissipation of Chiral
Fungicide Triticonazole in Agricultural Management.
AB - Research interest in chiral pesticides has increased probably because enantiomers
often exhibit different environmental fate and toxicity. An investigation into
the enantiomer-specific bioactivity of chiral triticonazole enantiomers in
agricultural systems revealed intriguing experimental and theoretical evidence.
For nine of the phytopathogens studied ( Rhizoctonia solani, Fusarium
verticillioide, Botrytis cinerea (strawberry and tomato), Rhizoctonia cereali,
Alternaria solani, Gibberella zeae, Sclerotinia sclerotiorum, and Pyricularia
grisea), the fungicidal activity data showed ( R)-triticonazole was 3.11-82.89
times more potent than the ( S) enantiomer. Furthermore, ( R)-triticonazole
inhibited ergosterol biosynthesis and cell membrane synthesis 1.80-7.34 times
higher than its antipode. Homology modeling and molecular docking studies
suggested the distinct bioactivities of the enantiomers of triticonazole were
probably due to their different binding modes and affinities to CYP51b. However,
field studies demonstrated that ( S)-triticonazole was more persistent than ( R)
triticonazole in fruits and vegetables. The results showed that application of
pure ( R)-triticonazole, with its high bioactivity and relatively low resistance
risk, instead of the racemate in agricultural management would reduce the
application dosage required to eliminate carcinogenic mycotoxins and any
environmental risks associated with this fungicide, yielding benefits in food
safety and environmental protection.
PMID- 29944366
TI - Design of a New Glutamine-Fipronil Conjugate with alpha-Amino Acid Function and
Its Uptake by A. thaliana Lysine Histidine Transporter 1 ( AtLHT1).
AB - Creating novel pesticides with phloem mobility is essential for controlling
insects in vascular tissue and root, and conjugating existing pesticides with
amino acid is an effective approach. In order to obtain a highly phloem-mobile
candidate for efficient pesticides, an electro-neutral l-glutamine-fipronil
conjugate (l-GlnF) retaining alpha-amino acid function was designed and
synthesized to fit the substrate specificity of an amino acid transporter.
Cotyledon uptake and phloem loading tests with Ricinus communis have verified
that l-GlnF was phloem mobile, and its phloem mobility was higher than that of
its enantiomer d-GlnF and other previously reported amino acid-fipronil
conjugates. Inhibition experiments then suggested that the uptake of l-GlnF was,
at least partially, mediated by an active transport mechanism. This inference was
further strengthened by assimilation experiments with Xenopus oocytes and
genetically modified Arabidopsis thaliana, which showed a direct correlation
between the uptake of l-GlnF and the expression of amino acid transporter AtLHT1.
Thus, conjugation with l-Gln appears to be a potential strategy to ensure the
uptake of pesticides via an endogenous amino acid transport system.
PMID- 29944369
TI - Additive Tuned Selective Synthesis of Bicyclo[3.3.0]octan-1-ols and
Bicyclo[3.1.0]hexan-1-ols Mediated by AllylSmBr.
AB - The selective construction of bicyclo[3.3.0]octan-1-ols and bicyclo[3.1.0]hexan-1
ols was achieved by using an allylSmBr/additive(s) system. By employing HMPA as
the only additive, the momoallylation/ketone-alkene coupling occurred preferably
and afforded bicyclo[3.3.0]octan-1-ols in good yields with high
diastereoselectivities. While the ester-alkene coupling predominated to generate
bicyclo[3.1.0]hexan-1-ols in moderate yields with excellent
diastereoselectivities in the presence of a proton source, such as pyrrole as the
coadditive with HMPA. The tunable reactivity of allylSmBr by additive(s) would
make it a versatile reagent in organic synthesis.
PMID- 29944370
TI - Izenamides A and B, Statine-Containing Depsipeptides, and an Analogue from a
Marine Cyanobacterium.
AB - Izenamides A, B, and C (1-3), new linear depsipeptides, were isolated from a
taxonomically distinct marine cyanobacterium. Izenamides A and B contain a
statine moiety [(3 S,4 S)-4-amino-3-hydroxy-6-methylheptanoic acid] and inhibited
the activity of cathepsin D, an aspartic peptidase. Meanwhile, izenamides did not
show growth-inhibitory activity against HeLa, HL60, or MCF-7 cells at up to 10
MUM.
PMID- 29944371
TI - Discovery of Potent, Selective, and Peripherally Restricted Pan-Trk Kinase
Inhibitors for the Treatment of Pain.
AB - Hormones of the neurotrophin family, nerve growth factor (NGF), brain derived
neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), are
known to activate the family of Tropomyosin receptor kinases (TrkA, TrkB, and
TrkC). Moreover, inhibition of the TrkA kinase pathway in pain has been
clinically validated by the NGF antibody tanezumab, leading to significant
interest in the development of small molecule inhibitors of TrkA. Furthermore,
Trk inhibitors having an acceptable safety profile will require minimal brain
availability. Herein, we discuss the discovery of two potent, selective,
peripherally restricted, efficacious, and well-tolerated series of pan-Trk
inhibitors which successfully delivered three candidate quality compounds 10b,
13b, and 19. All three compounds are predicted to possess low metabolic clearance
in human that does not proceed via aldehyde oxidase-catalyzed reactions, thus
addressing the potential clearance prediction liability associated with our
current pan-Trk development candidate PF-06273340.
PMID- 29944372
TI - Identification of Morpholino Thiophenes as Novel Mycobacterium tuberculosis
Inhibitors, Targeting QcrB.
AB - With the emergence of multidrug-resistant strains of Mycobacterium tuberculosis
there is a pressing need for new oral drugs with novel mechanisms of action.
Herein, we describe the identification of a novel morpholino-thiophenes (MOT)
series following phenotypic screening of the Eli Lilly corporate library against
M. tuberculosis strain H37Rv. The design, synthesis, and structure-activity
relationships of a range of analogues around the confirmed actives are described.
Optimized leads with potent whole cell activity against H37Rv, no cytotoxicity
flags, and in vivo efficacy in an acute murine model of infection are described.
Mode-of-action studies suggest that the novel scaffold targets QcrB, a subunit of
the menaquinol cytochrome c oxidoreductase, part of the bc1-aa3-type cytochrome c
oxidase complex that is responsible for driving oxygen-dependent respiration.
PMID- 29944374
TI - Self-Assembly of alpha-Tocopherol Transfer Protein Nanoparticles: A Patchy
Protein Model.
AB - We describe the mechanism of self-aggregation of alpha-tocopherol transfer
protein into a spherical nanocage employing Monte Carlo simulations. The protein
is modeled by a patchy coarse-grained representation, where the protein-protein
interfaces, determined in the past by X-ray diffraction, are represented by
simplified two-body interaction potentials. Our results show that the
oligomerization kinetics proceeds in two steps, with the formation of metastable
trimeric units and the subsequent assembly into the spherical aggregates. Data
are in agreement with experimental observations regarding the prevalence of
different aggregation states at specific ambient conditions. Finally, our results
indicate a route for the experimental stabilization of the trimer, crucial for
the understanding of the physiological role of such aggregates in vitamin E body
trafficking.
PMID- 29944373
TI - Ehrenfest Statistical Dynamics in Chemistry: Study of Decoherence Effects.
AB - In previous works, we introduced a geometric route to define our Ehrenfest
statistical dynamics (ESD) and we proved that, for a simple toy model, the
resulting ESD does not preserve purity. We now take a step further: we
investigate decoherence and pointer basis in the ESD model by considering some
uncertainty in the degrees of freedom of a simple but realistic molecular model,
consisting of two classical cores and one quantum electron. The Ehrenfest model
is sometimes discarded as a valid approximation to nonadiabatic coupled quantum
classical dynamics because it does not describe the decoherence in the quantum
subsystem. However, any rigorous statistical analysis of the Ehrenfest dynamics,
such as the described ESD formalism, proves that decoherence exists. In this
article, decoherence in ESD is studied by measuring the change in the quantum
subsystem purity and by analyzing the appearance of the pointer basis to which
the system decoheres, which for our example is composed of the eigenstates of the
electronic Hamiltonian.
PMID- 29944375
TI - Monitoring Ultrafast Spin Crossover Intermediates in an Iron(II) Complex by Broad
Band Stimulated X-ray Raman Spectroscopy.
AB - The photoinduced spin crossover dynamics of transition metal complexes is of
fundamental scientific importance and is used for sensor device applications and
solar energy harvesting. Current X-ray and optical spectroscopy experiments for
[FeII(bpy)3], an archetypal earth-abundant metal complex, show conflicting spin
dynamics. We have simulated the broad band transient X-ray absorption and hybrid
(broad + narrow band) X-ray stimulated Raman signals at the N and Fe K-edges of
the key excited state intermediates involved in the spin crossover process of
this complex. We find that these signals are much more sensitive to electron and
spin populations than transition absorption and may be useful in the design of
photovoltaic and artificial photosynthetic systems.
PMID- 29944376
TI - Direct Computation of the Quantum Partition Function by Path-Integral Nested
Sampling.
AB - In the present work we introduce a computational approach to the absolute
rovibrational quantum partition function using the path-integral formalism of
quantum mechanics in combination with the nested sampling technique. The
numerical applicability of path-integral nested sampling is demonstrated for
small molecules of spectroscopic interest. The computational cost of the method
is determined by the evaluation time of a point on the potential energy surface
(PES). For efficient PES implementations, the path-integral nested sampling
method can be a viable alternative to the direct-Boltzmann-summation technique of
variationally computed rovibrational energies, especially for medium-sized
molecules and at elevated temperatures.
PMID- 29944377
TI - Extending the Lotus Effect: Repairing Superhydrophobic Surfaces after
Contamination or Damage by CHic Chemistry.
AB - Superhydrophobic surfaces have gained a reputation to show a self-cleaning
behavior ("Lotus effect") as drops rolling off the surface take along loosely
adhering dust particles. However, this self-cleaning process reaches its limits
when such surfaces are brought in contact with sticky contaminants such as oils
and smaller particles. Once intimate contact is established between the surface
and a small particle, it will be almost impossible to remove it because of strong
surface interactions. Such contaminations, however, lead to contact line pinning
and destroy the superhydrophobic effect. Because the fragility of the micro- and
nanostructures prohibits any mechanical cleaning, the sample is usually doomed.
Here, we report a universal method for restoring superhydrophobicity: by simple
dip-coating, a conformal ultrathin layer (~10 nm) of a highly hydrophobic and
photoreactive fluoropolymer is deposited. Through short UV irradiation (5 min),
this thin layer is cross-linked and chemically attached to the underlying surface
by C,H-insertion cross-linking, thus covering the contaminant like a thin veil.
We use this "cover-up" strategy of masking the contaminants to restore
superhydrophobicity. We demonstrate this principle by deliberately soiling the
surface with various model contaminants, such as oily substances and particles,
and study the repair process.
PMID- 29944378
TI - Preclinical Efficacy of Anti-RON Antibody-Drug Conjugate Zt/g4-MMAE for Targeted
Therapy of Pancreatic Cancer Overexpressing RON Receptor Tyrosine Kinase.
AB - Aberrant expression of the RON receptor tyrosine kinase, a cell surface protein,
is a pathogenic feature in pancreatic cancer, which renders it a drug target for
targeted therapy. Nevertheless, development of therapeutics targeting RON for
pancreatic cancer therapy is hampered due to the lack of full addiction by
pancreatic cancer cells to RON signaling for growth and survival. Here we
describe a novel strategy using anti-RON antibody-directed drug delivery in the
form of an antibody-drug conjugate for inhibition and/or eradication of
pancreatic cancers. Monoclonal antibody Zt/g4 specific to the RON Sema domain was
selected as the drug carrier based on its ability to induce robust RON
internalization. Conjugation of Zt/g4 with monomethyl auristatin E, designated as
Zt/g4-MMAE, was achieved through a protease-sensitive dipeptide linker to reach a
drug to antibody ratio of 3.29:1. Zt/g4-MMAE was stable in human plasma with a
dissociation rate less than 4% within a 10 day period. In vitro, Zt/g4-MMAE
rapidly induced RON internalization, resulting in cell cycle arrest followed by
massive cell death. The maximal effect was seen in pancreatic cancer cells with
more than 10 000 receptor molecules per cell. Zt/g4-MMAE also synergized in vitro
with chemotherapeutics including gemcitabine, 5-fluorouracil, and oxaliplatin to
further reduce PDAC cell viability. In vivo, Zt/g4-MMAE exerts a long-lasting
activity, which not only inhibited but also eradicated pancreatic xenograft
tumors. These finding indicate that Zt/g4-directed drug delivery is highly
effective for eradicating pancreatic tumors. Thus, Zt/g4-MMAE is a novel
biotherapeutic with potential for therapy of RON-expressing pancreatic
malignancies.
PMID- 29944379
TI - Elementary Derivation of the "|DeltaMU| Big Is Good" Rule.
AB - Thirty years ago, Parr and Yang postulated that favorable chemical processes are
associated with large changes in the electronic chemical potential or,
equivalently, the electronegativity. They called this the "|DeltaMU| big is good"
rule and noted that if the rule could be justified, then it "would constitute a
validation of frontier theory from first principles." We provide a simple and
insightful justification for the "|DeltaMU| big is good" rule, with special
emphasis on electron-transfer reactions. Furthermore, we show that it implies
Pearson's hard/soft acid/base principle mathematically and confirm this result
with numerical examples. This supports Parr's intuition that many other
reactivity precepts arise as corollaries to the more fundamental "|DeltaMU| big
is good" rule. In all of this, it is essential to consider the intensive nature
of the chemical potential.
PMID- 29944380
TI - One-Step Conversion of Potassium Organotrifluoroborates to Metal
Organoborohydrides.
AB - This letter describes the one-step conversion of heteroatom-substituted potassium
organotrifluoroborates (KRBF3) to metal monoorganoborohydrides (MRBH3) using
alkali metal aluminum hydrides. The method tolerates a variety of functional
groups, expanding MRBH3 diversity. Hydride removal with Me3SiCl in the presence
of dimethylaminopyridine (DMAP) affords the organoborane.DMAP (RBH2.DMAP)
adducts.
PMID- 29944381
TI - Material Dimensionality Effects on Electron Transfer Rates Between CsPbBr3 and
CdSe Nanoparticles.
AB - Films containing mixtures of zero- or two-dimensional nanostructures (quantum
dots or nanoplatelets) were prepared in order to investigate the impacts of
dimensionality on electronic interactions. Electron transfer from CsPbBr3 to CdSe
was observed in all of the mixtures, regardless of particle dimensionality, and
characterized via both static and transient absorption and photoluminescence
spectroscopies. We find that mixtures containing nanoplatelets as the electron
acceptor (CdSe) undergo charge transfer more rapidly than those containing
quantum dots. We believe the faster charge transfer observed with nanoplatelets
may arise from the extended spatial area of the CdSe nanoplatelets and/or the
continuous density of acceptor states that are present in nanoplatelets. These
results bolster the use of one- or two-dimensional nanomaterials in the place of
zero-dimensional quantum dots in the design of related optoelectronic devices
such as solar cells, light-emitting diodes, and photocatalysts and further offer
the prospect of fewer required hopping events to transport carriers due to the
larger spatial extent of the particles.
PMID- 29944382
TI - Selective Synthesis of 3-Substituted Pyrrolidinones by Enol-Passerini and
Anomalous Enol-Passerini Condensations.
AB - Enols are used for the first time in a condensation with aldehydes and
isocyanides to selectively give three- or pseudo-four-component adducts,
depending on the reaction conditions. These new transformations have proven to be
a convenient alternative for the synthesis of biologically relevant
pyrrolidinones containing peptidic or pseudo-peptidic groups on carbon 3. More
importantly, this work attests to the utility of heterocyclic enols containing
conjugated electron-withdrawing groups as useful reagents in isocyanide-based
multicomponent reactions.
PMID- 29944383
TI - Palladium-Catalyzed Site-Selective Amidation of Dichloroazines.
AB - A highly site-selective amidation reaction of substituted 2,4-dichloroazines is
reported. Palladium acetate/1,1'-bis(diphenylphosphino)ferrocene (dppf) was
identified as the optimal catalyst system, producing >99:1 C-2/C-4 selectivity
for most examples. The generality of this transformation was demonstrated through
a survey of a diverse amide/substituted 2,4-dichloroazine scope, leading to the
preparation of the desired C-2 amidated products in good to excellent yields.
PMID- 29944384
TI - Clinical Characteristics and Predictors of Reduced Survival for Adult-diagnosed
Cystic Fibrosis. Analysis of the Canadian CF Registry.
AB - RATIONALE: Individuals diagnosed with cystic fibrosis (CF) as adults represent a
growing subpopulation of CF cases, but there are limited studies describing their
characteristics and prognosis. OBJECTIVES: The objectives of this study were to
describe the clinical characteristics of individuals with adult-diagnosed CF,
estimate survival rates in this population, and identify clinical predictors of
reduced survival at baseline. METHODS: The Canadian CF Patient Registry was used
to identify patients with CF who were >=18 years of age at diagnosis and received
a diagnosis between 1990 and 2014. Clinical characteristics were described and
the Kaplan-Meier method was used to estimate lung-transplant-free survival.
Multivariable Cox regression analysis and adjusted survival curves were employed
to identify important predictors of reduced survival at the time of diagnosis
(i.e., baseline) and to produce adjusted effects. RESULTS: A total of 362 adults
were diagnosed with CF during the study period. The median follow-up time was 7.7
years and 48 individuals experienced an event (15 transplants, 33 deaths without
transplant). The median age at diagnosis was 34.3 years, with the majority of
individuals presenting with pulmonary and/or gastrointestinal symptoms (71%).
Lung-transplant-free survival was 88% at 10 years and 86% at 15 years. Age at
diagnosis (hazard ratio [HR], 1.24 per 5-year increase, 95% confidence interval
[CI], 1.09-1.43), diabetes (HR, 4.19; 95% CI, 1.35-13.01), and lung function (HR,
1.35 per 5% decrease in forced expiratory volume in 1 second % predicted; 95% CI,
1.24-1.48) at baseline were important predictors of reduced survival.
CONCLUSIONS: CF care providers can use this information to inform individuals who
received a diagnosis of CF as adults about their prognosis and to guide the
necessity of treatments, specifically with regard to those who are at high risk
for a worse prognosis.
PMID- 29944385
TI - Validation of the V49.86 Code for Do-Not-Resuscitate Status in Hospitalized
Patients at a Single Academic Medical Center.
PMID- 29944386
TI - Actigraphy to Evaluate Sleep in the Intensive Care Unit. A Systematic Review.
AB - RATIONALE: Poor sleep quality is common in the intensive care unit (ICU) and may
be associated with adverse outcomes. Hence, ICU-based efforts to promote sleep
are gaining attention, motivating interest in methods to measure sleep in
critically ill patients. Actigraphy evaluates rest and activity by
algorithmically processing gross motor activity data, usually collected by a
noninvasive wristwatch-like accelerometer device. In critically ill patients,
actigraphy has been used as a surrogate measure of sleep; however, its use has
not been systematically reviewed. OBJECTIVES: To conduct a systematic review of
ICU-based studies that used actigraphy as a surrogate measure of sleep, including
its feasibility, validity, and reliability as a measure of sleep in critically
ill patients. METHODS: We searched PubMed, EMBASE, CINAHL, Proquest, and Web of
Science for studies that used actigraphy to evaluate sleep in five or more
patients in an ICU setting. RESULTS: Our search yielded 4,869 citations, with 13
studies meeting eligibility criteria. These 13 studies were conducted in 10
countries, and eight (62%) were published since 2008. Across the 13 studies, the
mean total sleep time of patients in the ICU, as estimated using actigraphy,
ranged from 4.4 to 7.8 hours at nighttime and from 7.1 to 12.1 hours over a 24
hour period, with 1.4 to 49.0 mean nocturnal awakenings and a sleep efficiency of
61 to 75%. When compared side-by-side with other measures of sleep
(polysomnography, nurse assessments, and patient questionnaires), actigraphy
consistently yielded higher total sleep time and sleep efficiency, fewer
nighttime awakenings (vs. polysomnography), and more overall awakenings (vs.
nurse assessment and patient questionnaires). None of the studies evaluated the
association between actigraphy-based measures of sleep and outcomes of patients
in the ICU. CONCLUSIONS: In critically ill patients, actigraphy is being used
more frequently as a surrogate measure of sleep; however, because actigraphy only
measures gross motor activity, its ability to estimate sleep is limited by the
processing algorithm used. Prior ICU-based studies involving actigraphy were
heterogeneous and lacked data regarding actigraphy-based measures of sleep and
patient outcomes. Larger, more rigorous and standardized studies are needed to
better understand the role of actigraphy in evaluating sleep and sleep-related
outcomes in critically ill patients.
PMID- 29944387
TI - Cigarette Smoking Impairs the Bioenergetic Immune Response to Mycobacterium
tuberculosis Infection.
AB - Smoking is a major risk factor driving the tuberculosis epidemic, and smokers'
alveolar macrophages (AM) demonstrate significant immune defects after infection.
Recently, macrophage glycolytic reprogramming has emerged as crucial in the early
host immune response to Mycobacterium tuberculosis (Mtb) infection. In the
present study, we sought to compare baseline metabolic characteristics and the
glycolytic response to infection of human AM from smokers and nonsmokers. AM were
obtained at bronchoscopy, and extracellular flux analyses were performed to
determine baseline metabolic characteristics compared with human monocyte-derived
macrophages (MDM). Metabolic characterization of AM from smokers and nonsmokers
was performed similarly. After infection with Mtb, differences in glycolytic
response were measured by extracellular flux analyses and gene expression
analyses and correlated with production of glycolysis-driven IL-1beta and
prostaglandin E2. Similar experiments were performed in cigarette smoke extract
treated MDM as an alternative model. At baseline, human AM from nonsmokers have a
significantly lower extracellular acidification rate/oxygen consumption rate
ratio than MDM (P < 0.05), but they retain substantial glycolytic reserve.
Compared with nonsmokers' AM, smokers' AM demonstrate reduced metabolic activity,
reduced glycolytic reserve (P = 0.051), and reduced spare respiratory capacity (P
< 0.01). After infection with Mtb, smokers' AM have significantly reduced
glycolytic response, as measured by extracellular flux analyses (P < 0.05) and
glycolytic gene expression analyses. Cigarette smoke extract-treated MDM
similarly demonstrate reduced metabolic activity and reserves, as well as
impaired glycolytic response to infection. Human AM demonstrate metabolic
plasticity that allows glycolytic reprogramming to occur after Mtb infection. In
smokers, this metabolic reserve is significantly attenuated, with consequent
impairment of the glycolytic response to infection.
PMID- 29944388
TI - beta-Klotho deficiency shifts the gut-liver bile acid axis and induces hepatic
alterations in mice.
AB - beta-Klotho (encoded by Klb) is an obligate co-receptor mediating both fibroblast
growth factor (FGF)15 and FGF21 signaling. Klb-/- mice are refractory to
metabolic FGF15 and FGF21 action and exhibit derepressed (increased) bile acid
(BA) synthesis. Here, we deeply phenotyped male Klb-/- mice on a pure C57BL/6J
genetic background fed a chow diet, focusing on metabolic aspects. This aims to
better understand the physiological consequences of concomitant FGF15 and FGF21
signaling deficiency, in particular on the gut-liver axis. Klb-/- mice present
permanent growth restriction independent of adiposity and energy balance. Klb-/-
mice also exhibit few changes in carbohydrate metabolism, combining normal gluco
tolerance, insulin sensitivity and fasting response with increased gluconeogenic
capacity and decreased glycogen mobilization. Livers of Klb-/- mice reveal
pathologic features, including a pro-inflammatory status and initiation of
fibrosis. These defects are associated to a massive shift in BA composition in
the enterohepatic system and blood circulation featured by a large excess of
microbiota-derived deoxycholic acid (DCA), classically known for its genotoxicity
in the gastrointestinal tract. In conclusion, beta-Klotho is a gatekeeper of
hepatic integrity, through direct action (mediating FGF21 anti-inflammatory
signaling) and indirect mechanisms (mediating FGF15 signaling that maintain BA
level and composition).
PMID- 29944389
TI - Circulating extracellular vesicles are associated with lipid and insulin
metabolism.
AB - We have reported that hypertrophic adipocytes release extracellular vesicles
(EVs) and the number of circulating adipocyte-derived EVs correlated with insulin
and homeostasis model assessment-insulin resistance (HOMA-IR) in a pilot study
using obese patients. Here, we explored the association between circulating EV
level and various metabolic parameters, including obesity and lipid and glucose
metabolisms, among 203 subjects (76 men and 127 women; median age, 54 yr) with or
without risk factor for metabolic diseases, who received a 75-g oral glucose
tolerance test (OGTT). Circulating EV number was significantly higher in men than
in women ( P < 0.001). Circulating EV number in individuals with impaired OGTT
pattern was significantly higher compared with those with normal OGTT patterns (
P < 0.05). Multiple regression analysis revealed that circulating EV number
correlated most strongly and significantly with elevated triglyceride (TG; t =
8.55, P < 0.001). Additionally, circulating EV number correlated significantly
with homeostasis model assessment-beta-cell function (HOMA-beta; t = 2.38, P <
0.05). Receiver operating characteristic curve revealed that the cutoff value of
EV numbers in individuals with elevated serum TG levels (?150 mg/dl) was
identified (136,738 EVs/MUl of plasma, P < 0.001, sensitivity 0.842, false
positive rate of 0.257). Perilipin and asialoglycoprotein receptor 1 were
detected on a part of isolated circulating EVs, indicating EV release from
adipocytes and hepatocytes, which were related to lipid and glucose metabolism.
Circulating EVs represent a promising metabolic biomarker for lipid and glucose
metabolism and have potential for monitoring metabolic status in humans,
including individuals without metabolic risk factors.
PMID- 29944390
TI - Oxytocin response to controlled dietary sodium and angiotensin II among healthy
individuals.
AB - Oxytocin, while classically known for its role in parturition, lactation, and
social behavior, also has been implicated in the control of sodium homeostasis in
animal models. To improve our understanding of oxytocin physiology in humans, we
measured basal oxytocin levels under low- and liberal-dietary-sodium conditions
and following a peripheral angiotensin II (ANG II) infusion. Ten healthy
individuals underwent a 6-day standardized low-sodium diet and a 6-day liberal
sodium diet. Each diet was followed by a graded ANG II infusion for 30-min
sequential intervals at doses of 0.3, 1.0, and 3.0 ng.kg-1.min-1. Fasting serum
oxytocin was assessed before and after ANG II infusion. Basal oxytocin levels
(1,498.5 +/- 94.7 vs. 1,663.3 +/- 213.9 pg/ml, P = 0.51) did not differ after the
low- and liberal-sodium diets. Following the ANG II infusion, ANG II levels and
mean arterial pressure significantly increased as expected. In contrast, the ANG
II infusion significantly lowered oxytocin levels from 1,498.5 +/- 94.7 vs.
1,151.7 +/- 118.1 pg/ml ( P < 0.001) on the low-sodium diet and from 1,663.3 +/-
213.9 vs. 1,095.2 +/- 87.4 pg/ml ( P = 0.03) on the liberal-sodium diet. The
percent change in oxytocin following the ANG II infusion did not differ by sodium
diet (-25 +/- 5% vs. -28 +/- 7% low- vs. liberal-sodium conditions, P > 0.99).
Dietary sodium intake did not affect circulating oxytocin levels among healthy
individuals. Systemic oxytocin levels were significantly suppressed following a
peripheral ANG II infusion independent of dietary sodium conditions.
PMID- 29944391
TI - ErbB4 deletion predisposes to development of metabolic syndrome in mice.
AB - ErbB4, a member of the EGF receptor family, plays a variety of roles in
physiological and pathological states. Genetic studies have indicated a link
between ErbB4 and type 2 diabetes and obesity, but its role in metabolic syndrome
(MetS) has not been reported. In the current study we found that mice with ErbB4
deletion developed MetS after 24 wk on a medium-fat diet (MFD), as indicated by
development of obesity, dyslipidemia, hepatic steatosis, hyperglycemia,
hyperinsulinemia, and insulin resistance, compared with wild-type mice. ErbB4
deletion mice also exhibited increased amounts of subcutaneous and visceral fat,
with increased serum leptin levels, compared with wild-type mice, whereas levels
of adiponectin were not significantly different. Histologically, severe
inflammation, indicated by F4/80 immunostaining and M1 macrophage polarization,
was detected in inguinal and epididymal white adipose tissue in ErbB4 deletion
mice. ErbB4 expression decreased during 3T3-L1 preadipocyte differentiation.
Administration of neuroregulin 4, a specific ligand for ErbB4, to 3T3-L1
adipocytes had no effect on adipogenesis and lipolysis but significantly
inhibited lipogenesis, promoted browning, induced GLUT4 redistribution to the
cell membrane, and increased glucose uptake. Neuroregulin 4 also significantly
increased glucose uptake in adipocytes isolated from wild-type mice, while these
effects were significantly decreased in adipocytes isolated from ErbB4 deletion
mice. In conclusion, our results indicate that ErbB4 may play an important role
in glucose homeostasis and lipogenesis. ErbB4 deficiency-related obesity and
adipose tissue inflammation may contribute to the development of MetS.
PMID- 29944393
TI - DNA Methylation Regulates RGS2-induced S100A12 Expression in Airway Epithelial
Cells.
AB - RGS2 is a key modulator of stress in human airway epithelial cells, especially of
hyperresponsiveness and mucin hypersecretion, both of which are features of
cystic fibrosis (CF). Because its expression can be modulated through the DNA
methylation pathway, we hypothesize that RGS2 is downregulated by DNA
hypermethylation in CF airway epithelial cells. This downregulation would then
lead to an enhanced inflammatory response. We demonstrated RGS2 transcript and
protein downregulation in cultured airway epithelial cells from patients with CF
and validated our findings in two CF epithelial cell lines. A methylated DNA
immunoprecipitation array showed the presence of methylated cytosine on 13 gene
promoters in CF. Among these genes, we confirmed that the RGS2 promoter was
hypermethylated by using bisulfite conversion coupled with a methylation-specific
PCR assay. Finally, we showed that downregulation of RGS2 in non-CF cells
increased the expression of S100A12, a proinflammatory marker. These results
highlight the importance of epigenetic regulation in gene expression in CF and
show that RGS2 might modulate the inflammatory response in CF through DNA
methylation control.
PMID- 29944392
TI - Leptin regulation of core body temperature involves mechanisms independent of the
thyroid axis.
AB - The ability to maintain core temperature within a narrow range despite rapid and
dramatic changes in environmental temperature is essential for the survival of
free-living mammals, and growing evidence implicates an important role for the
hormone leptin. Given that thyroid hormone plays a major role in thermogenesis
and that circulating thyroid hormone levels are reduced in leptin-deficient
states (an effect partially restored by leptin replacement), we sought to
determine the extent to which leptin's role in thermogenesis is mediated by
raising thyroid hormone levels. To this end, we 1) quantified the effect of
physiological leptin replacement on circulating levels of thyroid hormone in
leptin-deficient ob/ob mice, and 2) determined if the effect of leptin to prevent
the fall in core temperature in these animals during cold exposure is mimicked by
administration of a physiological replacement dose of triiodothyronine (T3). We
report that, as with leptin, normalization of circulating T3 levels is sufficient
both to increase energy expenditure, respiratory quotient, and ambulatory
activity and to reduce torpor in ob/ob mice. Yet, unlike leptin, infusing T3 at a
dose that normalizes plasma T3 levels fails to prevent the fall of core
temperature during mild cold exposure. Because thermal conductance (e.g., heat
loss to the environment) was reduced by administration of leptin but not T3,
leptin regulation of heat dissipation is implicated as playing a uniquely
important role in thermoregulation. Together, these findings identify a key role
in thermoregulation for leptin-mediated suppression of thermal conduction via a
mechanism that is independent of the thyroid axis.
PMID- 29944395
TI - Attenuation and Protection Efficacy of a Recombinant Infectious Laryngotracheitis
Virus (ILTV) Depleted of Open Reading Frame C (DeltaORFC) when Delivered in ovo.
AB - In an effort to produce more stable vaccines for infectious laryngotracheitis
virus (ILTV), recombinant strains with deletion of genes associated with
virulence have been evaluated for attenuation and protection efficacy. Among
viral genes associated with virulence, a cluster of five open reading frames
(ORFs; A through E) have been identified. An attenuated ILTV recombinant strain
with deletion of the ORF C gene induced protection comparable to that elicited by
the tissue culture origin (TCO) vaccine when administered via eyedrop. The
objective of this study was to evaluate the attenuation and protection efficacy
of the DeltaORF C strain when delivered in ovo to maternal antibody negative (MAb
) and maternal antibody positive (MAb+) embryos. In ovo delivery of the DeltaORF
C strain did not affected hatchability or body weight gain, while virus
transmission to contact chickens was minor. Nevertheless, nine of ninety (10%) of
MAb- chickens vaccinated with the DeltaORF C strain showed marked dyspnea, and
upon postmortem examination bloody mucoid plugs and high viral genome load were
detected in their tracheas. Moreover, the DeltaORF C strain induced satisfactory
protection in MAb- chickens, but marginal protection in MAb+ chickens after
challenge. The reduced protection observed for MAb+ groups of chickens was likely
caused by the interference of maternally derived antibodies. This report presents
the use of a genetically attenuated ILTV strain delivered in ovo as a potential
new approach in the control of ILTV.
PMID- 29944394
TI - Gross Morphometry, Histomorphometry, and Immunohistochemistry Confirm Early and
Persistent Jejunal Crypt Hyperplasia in Poults with Enteritis and Depressed
Growth.
AB - Phosphorylated histone 3 (PH3) and cleaved caspase 3 (CCASP3) were used to detect
proliferating and apoptotic cells, respectively, in the jejunums of female
sibling poults, with and without enteritis and depressed growth, from hatch to
day 35. Poults that developed enteritis and depressed growth (SIB flock) were
raised on a commercial farm in eastern North Carolina, whereas poults with normal
growth and no enteritis (TAU flock) were raised in the Teaching Animal Unit at
North Carolina State University College of Veterinary Medicine. Beginning on day
5 through day 35 and at processing, TAU poults were significantly heavier than
SIB poults. Jejunal weights, relative jejunal weights, and jejunal densities were
greater in SIB poults from day 10 through 35. Jejunal efficiency (body weight
/jejunal length) was higher in TAU poults at day 5 and days 10 through 35.
Mucosal thickness was greater in SIB poults between days 7 and 21 but greater in
TAU poults at days 28 and 35. From day 7 to 35, villus-to-crypt ratios were
higher for TAU poults and lower for SIB poults because hyperplastic crypts formed
a greater percentage of the mucosa in SIB poults. By day 7, PH3- and CCASP3
positive cells were increased in SIB poults, showing that mucosal changes
resulted from combined crypt epithelial hyperplasia and increased apoptosis of
villous enterocytes. Findings in this study confirm that enteritis, in the
absence of clinical signs, and depressed growth in turkey poults begins by day 7,
can be identified microscopically, persists for at least 35 days, is associated
with lower processing weights, and has a profound negative effect on turkey
growth.
PMID- 29944396
TI - Survey for Bacteria and Antimicrobial Resistance in Wild Turkeys ( Meleagris
gallopavo) in Ontario, Canada.
AB - Since being successfully reintroduced into Ontario, Canada, wild turkey (
Meleagris gallopavo) populations have undergone robust growth and range
expansion. This, along with increases in land use changes from human population
growth and subsequent developments in agriculture and livestock production, has
heightened opportunities for interactions between wild turkeys, domestic poultry,
and humans. As conspecifics, wild and domestic turkeys are susceptible to
infection and disease from many of the same pathogens. Thus, transmission by
direct or indirect contact is a potential health threat to both groups,
particularly with the overlapping range of wild turkeys in Ontario with numerous
commercial and backyard poultry operations. However, these threats are difficult
to assess due to knowledge gaps in the prevalence and geographic distribution of
potential pathogens circulating among wild turkeys. We assessed for potentially
pathogenic bacteria in free-ranging, hunter-harvested wild turkeys in Ontario ( n
= 152) by cloacal swab culture for Campylobacter spp., Salmonella spp., and
Escherichia coli and culture of lung and spleen for Pasteurella multocida,
Ornithobacterium rhinotracheale, and Erysipelothrix rhusiopathiae. Antimicrobial
resistance testing was also performed on E. coli isolates. Generic E. coli
isolates were recovered from 69.1% (105/152) of wild turkeys tested, and two
(1.9%) of these isolates exhibited resistance to azithromycin and one (1.0%) to
ampicillin. Intermediate susceptibility to chloramphenicol was observed in one
(1.0%) isolate. One (0.7%) wild turkey swab tested positive for C. jejuni, but no
samples were positive for P. multocida, Salmonella spp., O. rhinotracheale, or E.
rhusiopathiae. To our knowledge, this is the first survey of these bacteria and
assessment for antimicrobial resistance among wild turkeys in Ontario.
PMID- 29944397
TI - Virulence of Escherichia coli Isolates Obtained from Layer Chickens with
Colibacillosis Associated with Pericarditis, Perihepatitis, and Salpingitis in
Experimentally Infected Chicks and Embryonated Eggs.
AB - To evaluate the virulence of avian pathogenic Escherichia coli (APEC) isolates
obtained from colibacillosis cases associated with pericarditis, perihepatitis,
and salpingitis, the embryo lethality assay and experimental infection model in
chicks were used in this study. According to the established criteria based on
mortality in the embryo lethality assay for evaluating the virulence of E. coli
isolates, 23 of the 26 APEC isolates associated with pericarditis and
perihepatitis and 8 of the 20 isolates associated with salpingitis were found to
be virulent. Isolate D137, which had been obtained from a case with pericarditis
and perihepatitis and had an embryo mortality of 92%, and isolate D445, which had
been obtained from a case with pericarditis and perihepatitis and had an embryo
mortality of 17%, were used for the experimental infection. Four of the five 11
day-old chickens inoculated through the air sac with isolate D137 died 1 day
postinoculation, and the challenge strain was recovered from the air sac,
pericardial sac, or liver; however, colibacillosis lesions were found in only one
of the five birds postmortem. All five chicks inoculated with isolate D445
survived for 7 days postinoculation and exhibited airsacculitis or pericarditis
lesions at 7 days postinoculation; the challenge strain was not recovered from
the lesions postmortem. The results obtained in this study suggest that the
different APEC isolates tested cause illness in chickens through distinct
pathogenesis.
PMID- 29944398
TI - Streptococcosis in Commercial and Noncommercial Avian Species in California: 95
Cases (2000-2017).
AB - Streptococcal bacterial species represent common inhabitants of the intestinal
tract of animals and humans with a potential for opportunistic infections.
Streptococcosis has been identified in turkey poults ( Meleagris gallopavo),
ducklings and goslings (Anatidae), broiler chickens, semimature-adult chickens (
Gallus gallus domesticus), and young and adult pigeons (Columbidae). However, the
exact underlying factors that lead to bacterial invasion of the blood stream and
tissue colonization have not been completely elucidated. The electronic database
of the California Animal Health and Food Safety laboratory (Fresno, Tulare, and
Turlock branches) was searched for necropsy cases in which streptococcosis was
diagnosed in different avian species between January 2000 and August 2017. A
total of 95 cases, involving both commercial operations and noncommercial
premises, were analyzed. Streptococcus spp., Streptococcus bovis, and
Streptococcus gallolyticus were identified from multiple organs, with macroscopic
or histopathologic lesions (or both) indicative of septicemia in 23 (24%), 40
(42%), and 30 (32%) cases, respectively. Streptococcus pluranimalium and
Streptococcus lutetiensis were also isolated from one (1%) and two (2%) cases,
respectively. Turkey poults, broiler chickens, and ducklings were the most
commonly affected species with streptococcosis. Splenitis and hepatitis were the
most-common lesions observed and these were the organs with the highest isolation
rate. An overview of the clinical and pathologic presentation, and possible
predisposing conditions associated with this bacterial infection, is provided.
PMID- 29944399
TI - Genetic Characterization of Infectious Bursal Disease Viruses from Field
Outbreaks of the North East Region of India.
AB - In recent years, acute severe outbreaks of infectious bursal disease (IBD) are
frequently observed in commercial chicken populations of the North East Region
(NER) of India, resulting in huge economic loses to poultry farmers. Field
outbreaks of IBD in 30 different poultry farms in the NER were confirmed by
clinicopathologic examination and reverse transcriptase PCR. A total of 10
isolates of IBD virus (IBDV) from these outbreaks were characterized by the
genetic analysis of VP1 and the hypervariable region of the VP2 gene. Nucleotide
sequences, deduced amino acid sequences, and phylogenetic analysis of both VP2
and VP1 genes revealed two genetically diverse strains of very virulent IBDV
(vvIBDV) and one intermediate strain circulating in the NER. These isolates
differ at nucleotide and amino acid levels from vvIBDV isolates of mainland India
and are clustered in distinctly separate groups in the phylogenetic tree. Six of
the isolates revealed a unique combination of vvIBDV amino acid signatures in the
VP2 gene (A222, I256, I294), while bearing the non-vvIBDV amino acid signatures
of the VP1 gene (146E, 147G, 242D), but they are clearly classified as vvIBDV in
a phylogenetic analysis of both genes. Interestingly, one of the isolates showed
99% sequence homology with attenuated vaccine strains in the VP2 gene and
clustered together. This study demonstrates the diversity of IBDVs in India and
document for the first time the possible involvement of attenuated vaccine
strains in the epidemiology of IBD in India.
PMID- 29944400
TI - Bactericidal Efficacy of Food Additive-Grade Calcium Hydroxide Against Salmonella
Infantis on Eggshells.
AB - The bactericidal efficacy of food additive-grade calcium hydroxide [FdCa(OH)2]
was evaluated for inactivation of Salmonella Infantis and Salmonella Enteritidis
in liquid and Salmonella Infantis on contaminated eggshells. The activity of
FdCa(OH)2 was also compared with that of sodium hypochlorite (NaOCl) containing
150 ppm chlorine (150 ppm NaOCl). FdCa(OH)2 solutions (0.1% and 0.2%) in the
presence or absence of organic materials (5% calf serum [CS]) at pH 12.6 were
used to inactivate Salmonella Infantis and Salmonella Enteritidis in a reaction
tube or on eggshells artificially contaminated with Salmonella Infantis. Both
0.1% and 0.2% FdCa(OH)2 were capable of inactivating Salmonella Infantis and
Salmonella Enteritidis in liquid at >3 log10 colony-forming units (CFU)/ml within
3 and 1 min of contact time, respectively, even in the presence of 5% CS.
Additionally, 0.1% and 0.2% FdCa(OH)2 reduced bacterial levels on contaminated
eggshells to >3 log10 CFU/ml, within 3 and 1 min, respectively, in the presence
of 5% CS. Without CS, 0.1% and 0.2% FdCa(OH)2 could reduce bacteria on eggshells
to >3 log10 CFU/ml within 1 min and 30 sec, respectively. In contrast, 150 ppm
NaOCl solution could not inactivate bacteria on eggshells down to >3 log10 CFU/ml
within 3 min contact time, either with or without CS, and no bacterial reduction
was observed in redistilled water. The findings of the present study indicate
that FdCa(OH)2 solution has high efficacy against foodborne bacteria and may be a
good candidate for enhancement of biosecurity at farms and egg processing plants.
PMID- 29944401
TI - Expert Elicitation Provides a Rapid Alternative to Formal Case-Control Study of
an H7N9 Avian Influenza Outbreak in the United States.
AB - An expert elicitation was staged to rapidly decipher plausible routes and risks
of pathogen transmission in the 2017 H7N9 avian influenza (AI) outbreak in the
four-state region of Tennessee, Alabama, Georgia, and Kentucky. The process
included the identification of risk factors found in a preponderance of
commercial broiler breeder case farms over matched controls and an opinion-based
weighting of risks and mitigations perceived influential to this outbreak.
Although the two highly pathogenic AI case farms had general location and company
ownership in common, obvious connections were lacking for the remainder of H7N9
infected (all low pathogenicity) commercial farms. Expert elicitation of
differences between known cases and controls suggested a key role for
environmental rather than lateral (business network) pathways in the distribution
of low pathogenicity AI across commercial broiler breeder operations. Factors
with greatest strength as predictors of disease, whether or not they were causal,
included mesopredator or rodent incursions, enclosure defects, and habitat
disturbance that might attract wildlife to the farm (e.g., feed spills and
vacating of neighboring properties). Business affiliations that may have
facilitated farm-to-farm transfer, in contrast, were limited. Biosecurity
standards varied across this study group but were no more or less stringent among
cases over controls. However, results from a parallel hypothetical scenario
staged to address field data gaps suggest that uniformity and consistency in the
implementation of biosecurity practices may impact risk of disease introduction.
Importantly, this study was conducted within a few weeks and with little
disruption to emergency response activities. As such, the approach offers an
alternative model for interim field investigation of new or emerging high
consequence diseases with immediate decision support needs.
PMID- 29944402
TI - White Chick Syndrome Associated with Chicken Astrovirus in Ontario, Canada.
AB - Sixty-four cases of white chick syndrome (WCS) in broiler breeders producing
affected progeny were reported from seven hatcheries in Ontario, Canada, between
2009 and 2016, with 43 of those originating from two hatcheries owned by a single
company. WCS cases were identified by the presence of typical chicks in the
hatchery that were generally weak with pale to white down, enlarged abdomens, and
occasionally brown wiry fluff on the dorsum of the neck. Affected embryos and
chicks had characteristic gross and histologic liver lesions, and livers were
positive for chicken astrovirus (CAstV) RNA by real-time reverse transcriptase
PCR. Affected broiler breeder flocks experienced egg production drops of 0% to
21% and hatchability drops of 0% to 68.4%. The amino acid sequence of the region
encoding the capsid gene of WCS viruses demonstrated all Ontario CAstV to be in
Group B, Subgroup Bii.
PMID- 29944403
TI - Variant Serotypes of Fowl Adenovirus Isolated from Commercial Poultry Between
2007 and 2017 in Some Regions of China.
AB - The present study was performed to detect and characterize the serotypes of fowl
adenovirus associated with inclusion body hepatitis (IBH) or hepatitis
hydropericardium syndrome (HHS) in commercial poultry in some regions of China
between 2007 and 2017. Approximately 81 fowl adenovirus strains were isolated
from liver or kidney samples from diseased poultry. A sequencing analysis of the
hexon loop 1 gene revealed fowl adenovirus serotypes 8a, 8b, and 11 in samples of
broilers with IBH, serotype 11 in layers with IBH, and serotype 4 in poultry with
HHS. Of the fowl adenovirus serotype 4 strains, 62.07% were isolated from layers.
Additionally, 74.07% of the isolated strains were fowl adenovirus serotype 11
prior to June 2014; 53.70% were serotype 4 after that time point; and strains
isolated in the first half of 2017 were all serotype 8b, which was related to the
widespread application of inactivated serotype 4 adenovirus vaccines. These
results demonstrate that fowl adenovirus serotypes 11, 4, and 8b were the
predominant serotypes in some regions of China between 2007 and June 2014,
between June 2014 and 2016, and in the first half of 2017, respectively. Layers
were the predominant host infected with fowl adenovirus serotype 4 and could also
be infected by serotype 11.
PMID- 29944404
TI - Detection and Characterization of Circovirus in Canary Flocks.
AB - Circovirus infections have been documented in adult and nestling canaries
(Fringillidae) but the distribution of the virus in the world is not yet known.
In captive canary flocks, Circovirus infections have been reported based on the
clinical observations. In this study, the presence of both canary circovirus
(CaCV) and chicken anemia virus (CAV) in canary flocks was investigated. Virus
strains were detected by PCR and direct sequencing of amplified products.
Nucleotide sequences were aligned and compared with existing data in GenBank. PCR
identified CaCV-positive birds, giving an overall positivity rate of 25%, but all
samples were negative for CAV. According to the sequencing data, three distinct
strains were identified. Our results indicated a relationship between genetic
variation in the replicase gene ( rep) and the geographic regions as well as the
feasibility of using the rep gene for virus detection and molecular epidemiology
investigations. We are reporting detection and characterization of canary
circovirus based on the rep gene. Sequencing results and sequence identity
analysis revealed that the rep gene could be used for detecting and
discriminating the members of family Circoviridae. This manuscript is the first
report of canary circovirus in Iran and of three new strains in the world.
PMID- 29944405
TI - Using Multinomial and Space-Time Permutation Models to Understand the
Epidemiology of Infectious Bronchitis in California Between 2008 and 2012.
AB - Although infectious bronchitis virus (IBV) has been described as one of the most
economically important viral respiratory diseases in poultry, there are few
analyses of outbreaks that use spatial statistics. In order to better understand
how the different genotypes of IBV behave spatially and temporally, we used
geographic information system-based mapping coupled with spatial and spatial
temporal statistics to identify statistically significant clustering of multiple
strains of infectious bronchitis (IB) between 2008 and 2012 in California.
Specifically, space-time permutation and multinomial models were used to identify
spatial and spatial-temporal clusters of various genotypes of IBV. Using time
permutations (i.e., windows) spanning days to years, we identified three
statistically significant ( P < 0.05) clusters. In contrast, multinomial models
identified two statistically significant spatial-temporal clusters and one
statistically significant spatial cluster. When comparing the space-time
permutation and multinomial models against each other, we identified spatial and
temporal overlap in two of the three statistically significant clusters. From a
practical perspective, multinomial clustering approaches may be advantageous for
studying IB because the model allows the different genotypes of IB to be
independent nominal variables, thereby allowing for a more detailed spatial
analysis. To that point, based on their risk ratios, the genotypes classified as
vaccine-related were identified as the most significant contributor to two of the
three mutinomial clusters. Additionally, statistically significant clusters were
mapped and layered on a hot-spot analysis of commercial poultry farm density in
order to qualitatively assess the relationship between farm density and clusters
of IBV. Results showed that one of the three space-time permutations and one of
the three multinomial clusters were spatially centered near the highest density
farm areas, as determined by the hot-spot analysis.
PMID- 29944406
TI - Identification of Novel Linear Epitopes Located in the Infectious Bronchitis
Virus Spike S2 Region.
AB - We identified novel linear epitopes on the infectious bronchitis virus (IBV)
spike S2 region. The conformational structure of the IBV spike protein was
predicted from a homologous protein, human coronavirus NL63 spike. Although the
obtained structure was incomplete, most of the IBV spike protein structure was
predicted; the N-terminus of the S1 region could not be predicted due to its
variability. In the model, the region located in the proximity of the fusion
peptide appeared to be well conserved, and we evaluated the antigenicity of these
domains, which are involved in the membrane fusion machinery. Western blotting
revealed that IBV TM86 spike residues 686-723 were antigenic. Epitope mapping
analysis using synthesized peptides revealed that IBV TM86 spike 669-685
(SNFSTGAFNISLLLTPP), 686-697 (SNPRGRSFIEDL), and 692-703 (SFIEDLLFTSVE) residues
were major linear epitopes; two identified epitopes (686-697 and 692-703) were
covered by the fusion peptide, and the other epitope (669-685) was adjacent to
the fusion peptide. Although the identified epitopes are identically located as
the neutralizing epitope in severe acute respiratory syndrome coronavirus, the
recombinant protein that includes those epitopes could not elicit neutralizing
antibodies against IBV. This is the first report describing IBV spike S2 epitopes
located in the proximity of the fusion peptide, and it is suggested that the
spike fusion machinery of IBV may differ from that of severe acute respiratory
syndrome coronavirus, or, alternatively, IBV may have another mechanism to
penetrate the cell membrane.
PMID- 29944407
TI - Profiling of Egg Layer Flocks Affected with Focal Duodenal Necrosis Based on a
Questionnaire Survey.
AB - Focal duodenal necrosis (FDN) is an intestinal disease of egg-laying chickens,
characterized by multifocal mucosal erosions in the duodenal loop and proximal
jejunum. It is currently considered by the Association of Veterinarians in Egg
Production and the United States Animal Health Association as one of the top five
disease concerns of the table egg industry in the United States. Previous studies
have associated this condition with Clostridium species. The purpose of this
study was to investigate the epidemiologic characteristics of table egg layer
flocks affected with FDN. An online questionnaire was distributed to commercial
layer operations in different states in the United States. Layer farms that had
diagnosed FDN within the past 12 mo were surveyed. The questionnaire had 45
questions about management, nutrition, housing, and methods for disease
prevention and control. Thirty-seven surveys were sent and 21 were completed,
which represents a response rate of 56.7%. The survey results showed the presence
of FDN in five egg-layer genetic lines or breed crosses of different ages, with
most cases reported between 30-39 wk of age. The pullets were cage-reared in all
affected flocks and the majority of flocks in production were housed in
traditional cages. Most of the FDN-affected flocks received more than 12
different feed formulations from pre-lay to 60 wk of age. Distiller's dried grain
with solubles was a common ingredient added to the feed in the majority of
affected flocks, and all flocks were provided with limestone as a calcium source
for egg production. Most surveys reported that coccidiosis and roundworm
parasitism were not problems in affected flocks in production; however, pests
such as flies and rodents were reported as problems in most affected flocks.
Additionally, most affected farms never washed feeders, cages, and houses before
disinfection, which may not be sufficient to prevent the persistency and
transmission of the causative agent of FDN. In conclusion, several management
practices that have been associated with enteric disease, including clostridial
associated enteritis, were described by the majority of FDN-affected flocks.
Additional studies are needed to determine if management and health practices
identified in this survey represent risk factors for FDN.
PMID- 29944408
TI - Avian Influenza Virus Surveillance in High Arctic Breeding Geese, Greenland.
AB - The connectedness in Arctic regions between migratory waterbird populations
originating from different continents and the potential for virus exchange at
their shared Arctic breeding ground point to the need to explore the largely
unstudied circumpolar circulation of avian influenza viruses (AIV). We here
report the investigation of AIV in wild birds and lakes in a high Arctic area of
Northeast Greenland. No AIV could be detected in the fecal, feather, and water
samples collected from large flocks of pink-footed geese Anser brachyrhynchus and
barnacle geese Branta leucopsis in and around refuge lakes, where they congregate
at high density during their flightless molting period in summer.
PMID- 29944409
TI - Epidemic Characteristics of Clinical Histomoniasis in Chicken Flocks in Eastern
China.
AB - Preliminary diagnosis of clinical symptoms and gross lesions with subsequent
histopathologic and PCR analyses revealed histomoniasis in 276 chicken flocks in
Jiangsu Province, China, and surrounding areas from January 2012 to December
2015. Detailed statistical analysis was performed to explore the occurrence and
epidemic characteristics of histomoniasis in chicken flocks. The results
indicated that histomoniasis usually occurred in free-range flocks of local
broilers and laying hens. Also, 2- to 3-mo-old chickens were most susceptible to
infection, and adult chickens rarely developed infection. The morbidity rate of
chickens was generally 10%-30%, with mortality rates of less than 10%. Moreover,
histomoniasis is a seasonal disease, occurring most often from April to June, and
the rate of coinfection with heterakids in the ceca of infected chicken was
50.8%. The symptoms of diseased chickens included mental fatigue, bowing of the
head and wings, and yellowish green droppings, with bloody stool in very limited
cases. Most of the pathologic changes were characteristic of the disease, but
there were also some atypical lesions confirmed by laboratory techniques. In the
current study, the histomoniasis epidemic was first investigated in Chinese
chicken flocks, and the results provided a useful reference for further study of
this disease.
PMID- 29944411
TI - Premenstrual Psychosis in an Adolescent: A Case Report.
AB - Premenstrual psychosis is a rare phenomenon initiating during or preceding
menses, often lasting one to two weeks after the onset of menses. Previous
literature shows links between the estrogen decline of the menstrual cycle's late
luteal phase and the worsening of preexisting symptomatology in psychosis. There
is thought to be a similar etiology in premenstrual psychosis. Current literature
describes mostly clinical cases showing successful treatment using oral
contraceptives and/or atypical antipsychotics. We present an adolescent who
suffered from a new episode of psychosis beginning just before the onset of
menses. Her symptoms abated after the completion of menses and with the
initiation of combined oral contraceptives and olanzapine.
PMID- 29944412
TI - Methylphenidate as Treatment for Clozapine-Induced Sedation in Patients with
Treatment-Resistant Schizophrenia.
AB - BACKGROUND: Treatment-resistant schizophrenia patients frequently need to be
managed with clozapine. However, noncompliance is in-part due to complaints of
sedation, fatigue, and low energy. There is little literature reporting on the
effectiveness and safety of using stimulants to treat clozapine-induced sedation.
We report three cases of treatment-resistant schizophrenia where methylphenidate
was used to address these common side-effects. METHODS: To evaluate the
effectiveness and safety of psychostimulants in treatment-resistant
schizophrenia, we reviewed 3 extensively documented cases of clozapine-induced
sedation treated with methylphenidate for over 2 years, in addition to reviewing
the literature on this topic. RESULTS: All 3 patients reported improvements in
energy and fatigue, along with decreased sedation, while treated with
methylphenidate for 27, 30, and 32 months respectively. Clozapine doses ranged
between 325mg and 500mg daily; methylphenidate doses ranged between 2.5mg of the
immediate-release and 72mg daily of the extended-release formulation. There was
no reported or observed increase in psychotic symptoms resulting from treatment
with methylphenidate. CONCLUSION: Methylphenidate may be safe and effective in
the management of clozapine-induced sedation in treatment-resistant
schizophrenia. Large scale, placebo-controlled, double-blind trials are needed to
further validate the safety and efficacy of methylphenidate as treatment for
clozapine-induced sedation.
PMID- 29944413
TI - Faux-Pas Test: A Proposal of a Standardized Short Version.
AB - Previous research on theory of mind suggests that people with schizophrenia have
difficulties with complex mentalization tasks that involve the integration of
cognition and affective mental states. One of the tools most commonly used to
assess theory of mind is the Faux-Pas Test. However, it presents two main
methodological problems: 1) the lack of a standard scoring system; 2) the
different versions are not comparable due to a lack of information on the stories
used. These methodological problems make it difficult to draw conclusions about
performance on this test by people with schizophrenia. The aim of this study was
to develop a reduced version of the Faux-Pas test with adequate psychometric
properties. The test was administered to control and clinical groups. Interrater
and test-retest reliability were analyzed for each story in order to select the
set of 10 stories included in the final reduced version. The shortened version
showed good psychometric properties for controls and patients: test-retest
reliability of 0.97 and 0.78, inter-rater reliability of 0.95 and 0.87 and
Cronbach's alpha of 0.82 and 0.72.
PMID- 29944414
TI - An Exploratory Study of Exercise-related Effects on Memory and Hippocampal
Connectivity in Schizophrenia.
AB - Memory impairment in schizophrenia has been linked to abnormal functioning of
fronto-temporal networks. In this pilot study, we investigated whether 12-weeks
of exercise improved hippocampal-dependent memory functions and resting-state
functional connectivity in middle-aged adults with schizophrenia. The exercise
regimen was feasible, well-attended, and safe. There was a pre- to post
intervention increase in spatial memory accuracy that was correlated to an
increase in hippocampal-prefrontal cortex connectivity. No increase was found in
pattern separation performance or hippocampal volume. A controlled trial is
needed to replicate these findings and elucidate the functional brain networks
underlying exercise-induced cognitive improvement in schizophrenia.
PMID- 29944415
TI - THE USE OF LONG-ACTING ANTIPSYCHOTICS FOR THE MANAGEMENT OF AGGRESSIVENESS IN
SCHIZOPHRENIA: A CLINICAL OVERVIEW.
AB - Aggressive behaviour represents a challenge in the treatment of patients with
schizophrenia, being often associated with clinical predictors of severity of
illness such as poor insight, psychotic re-exacerbation, concomitant substance
misuse or comorbidity with personality disorders. As psychotic relapses and
consequent risk of aggressive behaviour are often associated with a poor
compliance, purpose of the present manuscript is to give an overview of the
available data about the use of depot antipsychotics for the management of
violence in patients with schizophrenia. A research in the main database sources
has been conducted to identify relevant papers about the topic. Few studies (most
of them retrospective and with small sample sizes) have investigated the
effectiveness of depot antipsychotic for the treatment of aggressive behaviour in
schizophrenia. Aripiprazole depot appears to be promising for the management of
aggressive behaviour of subjects with schizophrenia, however data about its
efficacy in the long-term are absent and lack of evidence prevents the
recommendation of this compound for the treatment of aggressiveness in subjects
affected by schizophrenia. In addition, there is not sufficient evidence to
conclude that a specific depot antipsychotic may have a better efficacy on
aggressive behaviour of patients affected by schizophrenia. Prospective
comparative studies (e.g. with oral clozapine and aripiprazole depot) are needed
to assess the real clinical advantage of the use of depot antipsychotic versus
oral alternatives for the prevention of violent behaviour in schizophrenia.
PMID- 29944416
TI - First-Episode Psychosis and Hypokalemia: A Case Report and Review of the
Literature.
AB - Hypokalemia is the most frequent electrolyte abnormality seen in clinical
practice. Hypokalemia is defined as serum potassium below 3.5 mEq/L and is
usually asymptomatic and only identified in routine laboratory analysis. However,
in some cases, symptoms include hypertension, palpitations, muscle weakness, easy
fatigability, cramping and myalgias, memory impairment, disorientation and
confusion, depressed or anxious mood, and irritability. Although rare,
hypokalemia has been associated with psychosis. In particular, hypokalemia has
been associated with psychotic exacerbations in patients with chronic psychotic
disorder. We present a case report of a young female who developed a first
presentation of acute psychosis and in which complementary investigations
revealed hypokalemia. The psychosis resolved in few hours after replacement
therapy with potassium chloride. The patient returned her usual functioning after
discharge and there were no signs of psychosis at six-month follow-up.
PMID- 29944417
TI - Neurocryptococcosis in immunocompetent patient with psychosis.
AB - BACKGROUND: The involvement of Cryptococcus as an etiological agent in behavioral
disorders, such as psychosis, is rare finding. METHODS: We report the case of 20
year-old man showed apparent functioning behavior premorbid, immunocompetent,
with had a first psychotic episode one day after a clinical condition by mild
fever, polyarthralgia, headache, fatigue and insomnia and detected cryptococcal
antigen latex and India ink positive for Cryptococus neoformans in lumbar
puncture. The psychotic episode responded to antifungal and antipsychotic
treatment. CONCLUSIONS: We emphasize the importance of paying attention to subtle
systemic and neurological signs and investigating the general medical condition
cause in the case of a first psychotic episode.
PMID- 29944418
TI - Re-titration rates after clozapine-induced neutropenia or agranulocytosis: A case
report and literature review.
AB - Clozapine-induced neutropenia occurs in 3-5% of individuals treated with
clozapine. Current US guidelines require interruption of clozapine when the
absolute neutrophil count (ANC) drops below 1000 cells/mm3. There is minimal
available guidance for what dosing schedule to use when restarting clozapine
after an episode of neutropenia. Here, we present a case of a 50-year-old
Caucasian female with a history of schizoaffective disorder who was successfully
rechallenged on clozapine one month after developing clozapine-induced
neutropenia (ANC 600 cells/mm3). To understand published re-titration rates of
clozapine after neutropenia, we conducted a literature review using a using the
PubMed database and found only seven case reports that unambiguously reported a
clozapine dosing schedule during re-challenge. All were successful except one, a
case of clozapine rechallenge after agranulocytosis. Including this case
presentation, six out of eight cases restarted clozapine more cautiously than
recommended by the US guidelines for a new clozapine initiation. We cannot
comment what role a slower or more rapid titration plays in a successful
rechallenge after neutropenia with the available evidence. We encourage
researchers to publish their dosing schedule in detail after an episode of
neutropenia or agranulocytosis.
PMID- 29944419
TI - Prevalence and clinical impact of childhood adversities in women with
schizophrenia.
AB - Patients with schizophrenia have higher rates of adverse childhood experiences
(ACEs) than the general population, and those who suffered multiple traumatic
experiences have a higher prevalence of positive symptoms, poorer social
functioning and more suicidal ideations and behavior. The current study aims to
determine the prevalence of ACEs in a female patient sample with schizophrenia.
An observational descriptive cross-sectional study was conducted. Participants
included 50 female patients older than 18 years, with schizophrenia. Semi
structured interviews and the Adverse Childhood Experiences Questionnaire were
conducted. We observed that 90% experienced at least one ACE. Most (52%) suffered
4 or more ACEs. A high prevalence of emotional abuse and neglect was found and a
significant relationship between patients who suffered multiple ACEs and the
presence of suicidal behavior and persistent auditory hallucinations.
PMID- 29944421
TI - Subjectivity and Catatonic Symptoms.
AB - Although recognized as a feature of schizophrenia since the time of Kraepelin,
motor disorders have received relatively little attention, particularly as regard
their phenomenology. This is particularly the case in the English-speaking
literature, where 'automaticity', mutism, and autonomic instability, have been
emphasized among the features of catatonia at the expense of more complex
behaviors and mannerisms. The possible relationship between the content of
thinking disorders, such as hallucinations and dereistic thinking, and
involuntary and semi-voluntary movement disorders, has been little noted. That
such gestures might have "intentionality", or meaning, has not been considered.
The case is presented of an adolescent who developed involuntary movements which
seemed to have meaning in reference to his interests. The thought content,
phenomenology, and brain abnormalities underpinning catatonia merit further
study.
PMID- 29944420
TI - When Dementia Kills Before One Passes Away: Case Report of Cotard's Syndrome.
AB - INTRODUCTION: Cotard's Syndrome (CS), among the noncognitive changes in the forms
of dementia, is a seldom-found manifestation (1). This syndrome is characterized
by the delusion of having lost organs (the individual experiences huge changes in
the body and believes that he/she no longer has one or more organs) and by
nihilistic delusion (the individual believes he/she or everyone in the world has
died or been destroyed) (2). In 1880, Jules Cotard (1840-1889) described a
clinical condition that he believed corresponded to a new subtype of depression,
which he called anxious melancholia. He proposed that a state of acute depression
and morbid anxiety could foster the development of structured delusions of
hypochondria. Two years later he referred to the same clinical condition using
the term delires des negations for the first time (3). The eponym CS was only
introduced in 1893 by Emil Regis, who stated that Cotard had not described a new
clinical entity but rather a syndrome - a cluster of symptoms that could also be
found in other mental illnesses apart from depression and in which anxiety was
the central characteristic (4). The most prominent symptoms found in an analysis
of one hundred cases were: depressed mood (89%), nihilistic delusion (69%),
anxiety (65%), delusion of guilt (63%), delusion of immortality (55%) and
hypochondriacal delusions (58%) (12). Currently, CS is not classified as an
isolated disorder in the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) of the American Psychiatric Association or in the International
Statistical Classification of Diseases and Related Health Problems (ICD-10).
There is a growing consensus to consider it a secondary syndrome of an underlying
disorder, of which the most associated disorders are: unipolar depression,
bipolar depression and primary psychotic disorders. Other conditions have also
been described, such as dementia, severe intellectual disability, cerebrovascular
accident, brain tumor, and Parkinson's disease, among others (5).
PMID- 29944422
TI - Exploring construct validity of clinical staging in schizophrenia spectrum
disorders in an acute psychiatric ward.
AB - OBJECTIVE: clinical staging and profiling of schizophrenia spectrum disorders has
been proposed to describe and define the heterogenous course of disease. We
examined the construct validity of clinical staging in schizophrenia spectrum
disorders by measuring differences in distribution and severity of relevant
clinical profilers and therapeutic improvement (HoNOS) across clinical stages.
METHODS: we performed a prospective cross-sectional study with 258 inpatients who
met DSM-IV criteria for schizophrenia spectrum disorders, recruited in an acute
ward of a psychiatric hospital from 1-1-2015 until 31-12-2016. All patients
(N=258) were assigned to a clinical stage, according to the criteria described by
McGorry and clinical profilers were determined. Therapeutic improvement was
assessed by measuring change in differences in HoNOS score during admission.
RESULTS: significant higher severity scores of clinical profilers were found in
more advanced stages compared to earlier stages. This pattern was apparent in the
clinical profilers negative symptoms (F=4.56, P<0.01), number of psychotic
episodes last year (F=13.65, P<0.01), compliance (F=2.76, P<0.05), work and daily
activities (F=9.85, P<0.001), living situation (F=3.71, P<0.05), support of close
relatives (F=9.38, P<0.001) and pre-morbid functioning (F=7.33, P<0.001).
Judicial background was less prevalent in earlier stages compared to more
advanced disease stages. No differences in therapeutic improvement (HoNOS) were
found between clinical stages. CONCLUSION: this study demonstrates that clinical
staging in schizophrenia spectrum disorders has an acceptable construct validity
between earlier and more chronic stages of disease. Several clinical profilers
increase in more advanced stages compared to earlier clinical stages, which
supports construct validity.
PMID- 29944423
TI - Psychiatric patient with Chilaiditi's syndrome.
AB - BACKGROUND: Chilaiditi's sign is defined as the interposition of bowels between
the liver and the right diaphragm. When the patient is symptomatic due to the
intestinal obstruction, the case is referred to as Chilaiditi's syndrome.
OBJECTIVE: To emphasize the importance of accurate diagnose of Chilaiditi's
syndrome in patients with psychotic disturbances. METHOD: A 46 years old male was
admitted to our department suffering from a constant epigastric and right upper
quadrant pain with radiation to the right shoulder. The pain started 10 hours
before the admission of the patient and was accompanied with vomiting. Patient
has a history of schizophrenia and intellectual disability. He was in a
stimulatory situation and unable to give any information about his state of
health. RESULTS: Patient was afebrile, tachycardic and laboratory results were
normal. The chest and abdomen x-ray showed the Chilaiditi's sign. With the
ultrasound procedure the case of the pneumoperitoneum was excluded. A
conservative treatment with IV fluid hydration, pain management, diet
modification, laxatives and enemas, was used. After a week of hospitalization,
the patient felt well, having proper diet and regular evacuations and at the
Chilaiditi's sign was no more observed. DISCUSSION: The etiology of the
Chilaiditi's syndrome is multifactoral and it has been reported that it is
associated with psychotropic medication and intellectual disability. CONCLUSIONS:
The diagnosis of the syndrome is vital in order to avoid unnecessary and
dangerous surgical interventions. Only few publications of a Chilaiditi syndrome
in patients with psychosis are cited in the literature.
PMID- 29944424
TI - Epidermolysis bullosa: management complexities for paediatric patients.
AB - : The genetic skin condition, epidermolysis bullosa (EB) causes the skin to be
fragile and blister. As a result, blisters need to be lanced and the skin needs
to be dressed with specialist dressings for protection and to promote wound
healing. METHOD: a prospective case series and product evaluation of the
AllevynTM Gentle Border Lite dressing range was conducted, with four paediatric
patients diagnosed with the following types of EB: recessive dystrophic
(generalised severe), dominant dystrophic, simplex (generalised severe) and
junctional (localised). Specialist EB nurses at Birmingham Children's Hospital
conducted the evaluation and compiled the case series. Management and outcomes:
clinical, patient and health economic outcomes were captured. The outcomes
reported suggest an increase in dressing time wear and a reduction in dressing
changes when comparing Allevyn Gentle Border Lite dressings to the patient's
regular foam dressing regime. Furthermore, a cost saving measure could be shown.
CONCLUSION: this small case series suggests that the use of the Allevyn Gentle
Border Lite dressing range can positively impact the clinical, patient and health
economic outcomes of paediatric EB patients.
PMID- 29944425
TI - EWMA 2018: a conference to remember.
PMID- 29944427
TI - Liverpool Heart and Chest Hospital's first tissue viability nurse consultant.
PMID- 29944426
TI - Target areas in wound care.
PMID- 29944428
TI - Mitigating the damaging effects of tissue distortions by using a low-friction
heel protector.
AB - This article reports the finding of a small non-controlled evaluation over a 2
week period in three different care settings: a residential care home, an acute
stroke unit and a community intermediate care hospital. At initial recruitment 30
patients were identified by clinical assessment as being at high risk of
developing a heel pressure ulcer. Further inclusion criteria were identifying
heels that had signs of pressure damage occurring, blanching and non-blanching
erythema, blistering and category 2 ulceration. In all, 15 patients fully
completed the evaluation over a 14-day period. The mean age was 86 years. The low
friction bootee was worn constantly while in bed and seated in chairs, only being
removed for heel checks and hygiene care. No patients were independently mobile
during the evaluation; products were not worn to walk in due to a risk of falling
patients in the community hospital who had to mobilise for rehabilitation removed
the bootees for this activity. All had pressure mapping and ultrasound of pedal
pulses prior and after evaluation by the tissue viability specialist nurse.
Results of pressure mapping showed a reduction of peak heel pressures on
application of the bootees and a final review of reduction in visual signs of
heel damage, reduced pain, increased comfort and ease of use. These results
indicate that a standardised care pathway approach to heel protection using low
friction heel bootees is effective in all care settings for the reduction and
prevention of heel pressure damage.
PMID- 29944429
TI - Moisture-associated skin damage: cause, risk and management.
AB - Understanding the differential diagnosis between moisture-associated skin damage
(MASD) and pressure ulcers (PU) ensures appropriate management and interventions
are instigated at the earliest opportunity. Most damage occurring to the buttocks
or sacrum is attributed to pressure, shear, excessive moisture or a combination
of these factors. MASD caused by excessive moisture to the sacrum/buttock area is
recognised as incontinence-associated dermatitis (IAD); its occurrence is an
identified risk factor in the development of PUs. Treatment for IAD should
therefore focus on both IAD management and pressure ulcer prevention.
PMID- 29944430
TI - Scars: impact and management, with a focus on topical silicone-based treatments.
AB - Many people are living with scars caused by surgery or traumatic injury. Scar
prevention in the early stages of wound healing is an essential aspect of care.
Ongoing scar management is generally by self-care, using non-invasive methods
such as silicone sheeting and/or massage. Silicone is considered to be the first
line non-invasive, prophylactic and therapeutic measure for scar management.
Nurses have a role in supporting patients with self-care of their scars as well
as providing psychological support, as the impact of a scar and effect of quality
of life can be significant.
PMID- 29944431
TI - Social support modifies the negative effects of acculturation on obesity and
central obesity in Mexican men.
AB - BACKGROUND: This study examined the moderating role of social support in the
acculturation-obesity/central obesity relationship in Mexican American (MA) men
and women. METHODS: Data from NHANES 1999-2008 were used. Acculturation derived
from language use, country of birth and length of residence in the U.S. Social
support assessed emotional and financial support. BMI (>=30) and waist
circumference (>=88 cm for women; >=102 cm for men) measured obesity and central
obesity, respectively. Weighted multivariate logistic regression models were used
to describe associations. RESULTS: Compared to less acculturation, more
acculturation was associated with higher odds of obesity (ORs 2.48; 95% CI 1.06
5.83) and central obesity (2.90; 1.39-6.08) among MA men with low/no social
support, but not among MA men reporting high social support. The modifying
effects was not observed among women. CONCLUSION: Higher amounts of social
support appeared to attenuate the risk of obesity/central obesity associated with
acculturation. Interventions enhancing social support maybe effective among
acculturated MAs, particularly among men.
PMID- 29944432
TI - Head postures during naturalistic driving.
AB - OBJECTIVE: A rotated head posture at the time of a rear-end impact is associated
with a higher risk of acute and chronic whiplash injury. The objective of this
study was to quantify the amplitude and duration of rotated head postures
observed in drivers during naturalistic driving. METHODS: Twenty volunteers (14
males: 36 +/- 12 years, 6 females: 27 +/- 5 years) drove a 2010 Subaru Impreza on
public roads while their 3D head angular position relative to the car was
recorded using inertial measurement units. An experimenter rode in the passenger
seat (right side) and logged when subjects performed one of 6 head movements:
Bilateral shoulder and side mirror checks, looking at the rearview mirror, and
looking at the front seat passenger. Video of the subjects was used to confirm
the logged head movements and identify movements that the experimenter missed.
The duration and amplitude of all 6 head movements were tabulated and then
compared between periods when the car was moving and when the car was stationary.
RESULTS: During a 68 +/- 5-min drive, subjects performed a median (range) of 15
(5-39) left shoulder checks, 82.5 (29-167) left mirror checks, 40.5 (10-168)
rearview mirror checks, 27.5 (3-113) right mirror checks, 60 (0-185) passenger
looks, and 12.5 (1-28) right shoulder checks. Peak yaw angles of the head
relative to the vehicle for these 6 movements averaged -81.5 degrees , -34.3
degrees , 16.2 degrees , 42.1 degrees , 58.2 degrees , and 84.3 degrees ,
respectively. Drivers spent a larger proportion of time in nonneutral postures
when the vehicle was stopped (17.5%) compared to moving (8.2%) (Z = 3.92, P <
.0001). Drivers also moved their head further from neutral during the movements
when the car was stationary compared to moving (t19 = 5.90, P < .0001).
CONCLUSIONS: Drivers use larger and longer duration head movements when
stationary than when driving. Given an increased risk of whiplash injury for
initially rotated head postures, these findings provide a possible explanation
for why drivers are more likely to be injured when hit from behind while their
vehicle is stationary. Further, the head postures characterized in this study can
be used as initial conditions in volunteer and computational studies to improve
our understanding of why nonneutral head postures are associated with increased
whiplash injury risk.
PMID- 29944433
TI - Temporal regulation of two cytosolic phosphoglucomutases during stigma
development in ornamental kale (Brassica oleracea var. acephala).
AB - Phosphoglucomutases (PGM) (5.4.2.2.) belong to the Phosphohexomutases superfamily
and are highly specific in catalyzing the interconversion of Glc-1-P to Glc-6-P.
In this study, we characterize the expression and activity of two cytosolic PGMs
(cPGM2 and cPGM3) stigmas of ornamental kale during flower development. In
stigmas, cPGM expression and activity showed a gradual increase during stigma
development with the highest activity around the time of anthesis. Blocking of
cPGM activity in the stigmas using a known inhibitor, resulted in breakdown of
self-incompatibility in immature S3 and S4 stigmas, but had no effect on the
fully mature S5 stigmas. It is likely that cPGMs are required for accumulation of
factors necessary for SI response in mature stigmas.
PMID- 29944434
TI - Core features of the hormonal status in in vitro grown potato plants.
AB - Some time ago, potato transformants expressing Agrobacterium-derived auxin
synthesis gene tms1 were generated. These tms1-transgenic plants, showing
enhanced productivity, were studied for their hormonal status, turnover and
responses in comparison with control plants. For this purpose, contents of
phytohormones belonging to six different classes (auxins, cytokinins,
gibberellins, abscisic, jasmonic and salicylic acids) were determined by a
sensitive UPLC-MS/MS method in tubers and shoots of in vitro grown plants. To
date, this study represents the most comprehensive analysis of the potato
hormonal system. On the basis of obtained results, several new generalizations
concerning potato hormonal status were drawn. Overall, these data can serve as a
framework for forthcoming integrative studies of the hormonal system in potato
plants.
PMID- 29944435
TI - Experiences of Inpatient Bone Marrow Transplantation Nurses and Providers Using
Electronic Symptom Reporting.
AB - PURPOSE: To investigate the use of electronic patient-reported outcomes (PROs) to
assess symptoms and how they can provide opportunities to clinicians to address
symptoms in a timely manner to improve clinical care. As part of a larger study
to evaluate whether providing standardized symptom reports to the medical team
would decrease the time to treatment of reported symptoms in hematopoietic stem
cell transplant recipients, we assessed nurses' and providers' perceptions of
electronic symptom reporting. METHODS: Semistructured interviews of RNs, MDs, NPs
and PAs were conducted at an academic cancer center in the southeastern United
States. Nurses' and providers' perceptions of electronic symptom reporting were
explored. Interviews were audio-recorded, transcribed, and coded by two
investigators to identify major themes. RESULTS: Fourteen RNs and seven providers
(MDs, PAs, and NPs) participated in the interviews. Three main themes emerged
from the interviews: electronic symptom reporting may improve assessment and
care, integrating symptom reporting into nurse workflow presents difficulties,
and there are barriers for completion of surveys. CONCLUSION: The majority of
nurses and providers believed that the inclusion of electronic symptom reporting
in bone marrow transplantation inpatient units has the potential to improve care
but that barriers to implementation remain.
PMID- 29944436
TI - Differential effects of light-to-dark transitions on phase setting in circadian
expression among clock-controlled genes in Pharbitis nil.
AB - The circadian clock is synchronized by the day-night cycle to allow plants to
anticipate daily environmental changes and to recognize annual changes in day
length enabling seasonal flowering. This clock system has been extensively
studied in Arabidopsis thaliana and was found to be reset by the dark to light
transition at dawn. By contrast, studies on photoperiodic flowering of Pharbitis
nil revealed the presence of a clock system reset by the transition from light to
dark at dusk to measure the duration of the night. However, a Pharbitis
photosynthetic gene was also shown to be insensitive to this dusk transition and
to be set by dawn. Thus Pharbitis appeared to have two clock systems, one set by
dusk that controls photoperiodic flowering and a second controlling
photosynthetic gene expression similar to that of Arabidopsis. Here, we show that
circadian mRNA expression of Pharbitis homologs of a series of Arabidopsis clock
or clock-controlled genes are insensitive to the dusk transition. These data
further define the presence in Pharbitis of a clock system that is analogous to
the Arabidopsis system, which co-exists and functions with the dusk-set system
dedicated to the control of photoperiodic flowering.
PMID- 29944437
TI - Deletion of TLS polymerases promotes homologous recombination in Arabidopsis.
AB - Unrepaired DNA damage hinders the maintenance of genome integrity because it
blocks the catalytic activity of replicase. The stalled replication fork can be
processed through either translesion synthesis (TLS) with specific polymerases,
or replication using the undamaged template. To investigate how TLS activities
are regulated and how the stalled replication fork is processed in plants,
reversion frequencies and homologous recombination (HR) frequencies were analyzed
using GUS-based substrates. The HR frequencies in plants deficient in DNA
polymerase zeta (Pol zeta) or Rev1 were higher than that in wildtype plants under
normal conditions, and were significantly increased by ultraviolet light
irradiation. Heat shock protein (HSP) 90 is known to be involved in various
stress responses. To examine the role of HSP90 in the regulation of damage
tolerance, we analyzed reversion frequencies and HR frequencies in plants grown
in the presence of a HSP inhibitor, geldanamycin (GDA). Reversion frequency was
lower in GDA-treated plants than in mock-treated plants. Though the HR frequency
was higher in GDA-treated wildtype plants than in mock-treated plants, no
significant difference was detected in Rev1-deficient plants. In yeast, TLS
polymerases interacted with each other or with a replication clump component,
proliferating cell nuclear antigen (PCNA). HSP90 interacted with REV1 or REV7 in
Nicotiana benthamiana cells. These results suggest that HSP90 interacts with TLS
polymerase(s), which promotes error-prone TLS in plants.
PMID- 29944438
TI - Biochemical control systems for small molecule damage in plants.
AB - As a system, plant metabolism is far from perfect: small molecules (metabolites,
cofactors, coenzymes, and inorganic molecules) are frequently damaged by unwanted
enzymatic or spontaneous reactions. Here, we discuss the emerging principles in
small molecule damage biology. We propose that plants evolved at least three
distinct systems to control small molecule damage: (i) repair, which returns a
damaged molecule to its original state; (ii) scavenging, which converts reactive
molecules to harmless products; and (iii) steering, in which the possible
formation of a damaged molecule is suppressed. We illustrate the concept of small
molecule damage control in plants by describing specific examples for each of
these three categories. We highlight interesting insights that we expect future
research will provide on those systems, and we discuss promising strategies to
discover new small molecule damage-control systems in plants.
PMID- 29944439
TI - Antibody pharmacokinetics in rat brain determined using microdialysis.
AB - Here, we present the first case-study where microdialysis is used to investigate
the pharmacokinetics of antibody in different regions of rat brain. Endogenous
IgG was used to understand antibody disposition at steady-state and exogenously
administered trastuzumab was used to understand the disposition in a dynamic
setting. Microdialysis samples from the striatum (ST), lateral ventricle (LV),
and cisterna magna (CM) were collected, along with plasma and brain homogenate,
to comprehensively understand brain pharmacokinetics of antibodies. Antibody
concentrations in cerebrospinal fluid (CSF) were found to vary based on the site
of-collection, where CM concentrations were several-fold higher than LV. In
addition, antibody concentrations in CSF (CM/LV) were found to not accurately
represent the concentrations of antibody inside brain parenchyma (e.g., ST).
Elimination of CSF from CM was found to be slower than LV, and the entry and exit
of antibody from ST was also slower. Pharmacokinetics of exogenously administered
antibody revealed that the entry of antibody into LV via the blood-CSF barrier
may represent an early pathway for antibody entry into the brain. Plasma
concentrations of antibody were 247-667, 104-184, 165-435, and 377-909 fold
higher than the antibody concentrations in LV, CM, ST, and brain homogenate. It
was found that the measurement of antibody pharmacokinetics in different regions
of the brain using microdialysis provides an unprecedented insight into brain
disposition of antibody. This insight can help in designing better molecules,
dosing regimens, and route of administration, which can in turn improve the
efficacy of antibodies for central nervous system disorders.
PMID- 29944440
TI - The clinical, immunological and microbiological impact of the 10-valent
pneumococcal-Protein D conjugate vaccine in children with recurrent protracted
bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: A
multi-centre, double-blind, randomised controlled trial.
AB - We aimed to determine the efficacy of the 10-valent pneumococcal-Haemophilus
influenzae protein D conjugate vaccine (PHiD-CV) in children aged 18-months to
<18-years with recurrent protracted bacterial bronchitis (rPBB), chronic
suppurative lung disease (CSLD) or bronchiectasis. In a multi-centre, double
blind randomised controlled trial, children received two doses, 2-months apart of
the 10vPHiD-CV or quadrivalent meningococcal-ACYW135 conjugate vaccine. Active
surveillance for acute exacerbations, respiratory symptoms and antibiotic use was
undertaken through to 12-months after the second vaccine dose (clinical cohort
only). Serum, saliva and nasopharyngeal swabs were collected to measure
immunological and microbiological effects (immunology cohort). Between December
2012 and August 2015, 62 children were enrolled onto the clinical protocol (1
excluded from clinical analyses due to unblinding), while 74 contributed to the
immunology cohort (overall mean age = 6.8-years (standard deviation = 3.7), 42
(56.8%) male). The absolute risk difference comparing the 10vPHiD-CV group (n =
31 children) to the MenACYW135 group (n = 30 children) for acute exacerbations
was -0.5 exacerbations/100-weeks at risk (95% confidence interval (CI) -2.0,
0.9). Compared to the MenACYW135 group, children who received the 10vPHiD-CV were
less likely to have respiratory symptoms in each fortnight of surveillance
(incidence density ratio (IDR) 0.82, 95%CI 0.61, 1.10) and required fewer short
course (<14-days duration) antibiotics (IDR 0.81, 95% CI 0.61, 1.09). The vaccine
was immunogenic and no serious adverse events related to the vaccine were
reported. In conclusion, 10vPHiD-CV might have a future role in managing children
with rPBB, CSLD and bronchiectasis, but larger multicentre trials are needed to
confirm or refute findings from this preliminary study.
PMID- 29944441
TI - Microwave radiation alters burn injury-evoked electric potential in Nicotiana
benthamiana.
AB - The dielectric effect enforced on charged ions and dipolar molecules by the
oscillating electric field of microwaves may influence electric signaling in
plants. In the present study, the exposure of Nicotiana benthamiana plants to
continuous wave 2.45 GHz microwave radiation with 1.9 - 2.1 W m-2 power density
significantly reduced the amplitude of leaf burning-induced variation potential
along the plant stem. The change in amplitude of the variation potential occurred
mainly because of a significant reduction of the depolarization rate. This effect
was not observed during the post-microwave exposure period. The unique
characteristics observed in the variation potentials were also observed under
microwave exposure, suggesting unaffected information delivery to distant
locations or unaffected transport of specific chemicals generated by the injury.
PMID- 29944442
TI - Effect of phosphate deficiency-induced anthocyanin accumulation on the expression
of Solanum lycopersicum GLABRA3 (SlGL3) in tomato.
AB - In Arabidopsis thaliana, the bHLH transcription factor, GLABRA3 (AtGL3), is an
important regulator of epidermal cell differentiation and positively controls
anthocyanin accumulation. In contrast, we previously showed that Solanum
lycopersicum GLABRA3 (SlGL3), the AtGL3 homolog, suppressed anthocyanin
accumulation in Arabidopsis. To clarify this functional discrepancy in
anthocyanin accumulation, we analyzed the SlGL3 expression pattern in anthocyanin
induced tomato. The SlGL3 expression was significantly reduced in tomato
seedlings rich in anthocyanin as a result of inorganic phosphate (Pi) starvation.
This was consistent with the previous result obtained in Arabidopsis, wherein the
overexpression of SlGL3 was shown to inhibit anthocyanin accumulation. Our study
suggests that the function of SlGL3 is different from that of AtGL3, and it might
inhibit anthocyanin accumulation in tomato.
PMID- 29944443
TI - New functions of an old kinase MPK4 in guard cells.
AB - Mitogen-activated protein kinase (MPK) cascades play important roles in plant
development, immune signaling and stress responses. MPK4 was initially identified
as a negative regulator in systemic acquired resistance (SAR) because the levels
of salicylic acid (SA) and reactive oxygen species (ROS) were higher in the
Arabidopsis mpk4 mutant. MPK4 is highly expressed in guard cells, specialized
epidermal cells forming stomatal pores on leaf surface that function at the
frontline of bacterial pathogen invasion. In addition to biotic stresses,
stomatal guard cells also mediate cellular responses to abiotic stimuli such as
drought and CO2 changes. MPK4 appears to play different roles in different plant
systems. In this review, we briefly discuss the protein kinase MPK4 functions and
focus on its signaling roles in different plant systems, especially in stomatal
guard cells.
PMID- 29944444
TI - AUXIN RESPONSE FACTOR3 plays distinct role during early flower development.
AB - AUXIN RESPONSE FACTOR3 (ARF3), one of the auxin response factors family of
transcription factors, is well characterized by its functions in polarity
identification and organ patterning. We recently demonstrated that ARF3 plays
important roles in floral meristem (FM) maintenance and termination by regulating
cytokinin biosynthesis and signaling. However, the relationship of its multiple
roles in differently developmental stage is still unclear. Here, we present data
that ARF3 plays distinct roles during early flower development that are different
from its roles in organ polarity determination and pattering. Thus, our findings
shed light on the functional diversity of one specific transcription factor in
plant development.
PMID- 29944445
TI - SlPRA1A/RAB attenuate EIX immune responses via degradation of LeEIX2 pattern
recognition receptor.
AB - Pattern recognition receptors (PRR) are plasma membrane (PM) proteins that
recognize microbe-associated molecular patterns (MAMPs), triggering an immune
response. PRR are classified as receptor like kinases (RLKs) or receptor like
proteins (RLPs). The PM localization of PRRs, which is crucial for their
availability to sense MAMPs, depends on their appropriate trafficking through the
endomembrane system. Recently, we have identified SlPRA1A, a prenylated RAB
acceptor type-1 (PRA1) from S. lycopersicum, as a regulator of RLP-PRR
localization and protein levels. SlPRA1A overexpression strongly decreases RLP
PRR protein levels, particularly those of LeEIX2, redirecting it to the vacuole
for degradation. Interestingly, SlPRA1A does not affect RLK-PRRs, indicating its
activity to be specific to RLP-PRR systems. As PRA1 proteins stabilize RABs on
membranes, promoting RABs activity, we aimed to identify a RAB target of SlPRA1A.
Screening of a set of A. thaliana RABs revealed that AtRABA1e is able to mimic
SlPRA1A activity. Through live cell imaging, we observed that SlPRA1A enhances
AtRABA1e localization on SlPRA1A positive punctuated structures. These results
indicate that AtRABA1e is a putative target of SlPRA1, and a co-regulator of
LeEIX2 trafficking and degradation.
PMID- 29944446
TI - Kinesin-dependent transport of keratin filaments: a unified mechanism for
intermediate filament transport.
AB - Keratin intermediate filaments (IFs) are the major cytoskeletal component in
epithelial cells. The dynamics of keratin IFs have been described to depend
mostly on the actin cytoskeleton, but the rapid transport of fully polymerized
keratin filaments has not been reported. In this work, we used a combination of
photoconversion experiments and clustered regularly interspaced short palindromic
repeats/clustered regularly interspaced short palindromic repeats-associated
protein 9 genome editing to study the role of microtubules and microtubule motors
in keratin filament transport. We found that long keratin filaments, like other
types of IFs, are transported along microtubules by kinesin-1. Our data revealed
that keratin and vimentin are nonconventional kinesin-1 cargoes because their
transport did not require kinesin light chains, which are a typical adapter for
kinesin-dependent cargo transport. Furthermore, we found that the same domain of
the kinesin heavy chain tail is involved in keratin and vimentin IF transport,
strongly suggesting that multiple types of IFs move along microtubules using an
identical mechanism.-Robert, A., Tian, P., Adam, S. A., Kittisopikul, M.,
Jaqaman, K., Goldman, R. D., Gelfand, V. I. Kinesin-dependent transport of
keratin filaments: a unified mechanism for intermediate filament transport.
PMID- 29944447
TI - A novel immunodeficient rat model supports human lung cancer xenografts.
AB - Patient-derived xenograft (PDX) animal models allow the exogenous growth of human
tumors, offering an irreplaceable preclinical tool for oncology research. Mice
are the most commonly used host for human PDX models, however their small body
size limits the xenograft growth, sample collection, and drug evaluation.
Therefore, we sought to develop a novel rat model that could overcome many of
these limitations. We knocked out Rag1, Rag2, and Il2rg in Sprague Dawley (SD)
rats by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR
associated protein 9 technology. The development of lymphoid organs is
significantly impaired in Rag1-/-Rag2-/-Il2rg-/Y (designated as SD-RG) rats.
Consequently, SD-RG rats are severely immunodeficient with an absence of mature
T, B, and NK cells in the immune system. After subcutaneous injection of tumor
cell lines of different origin, such as NCI-H460, U-87MG, and MDA-MB-231, the
tumors grow significantly faster and larger in SD-RG rats than in nonobese
diabetic- Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Most important of all, we
successfully established a PDX model of lung squamous cell carcinoma in which the
grafts recapitulate the histopathologic features of the primary tumor for several
passages. In conclusion, the severely immunodeficient SD-RG rats support fast
growth of PDX compared with mice, thus holding great potential to serve as a new
model for oncology research.-He, D., Zhang, J., Wu, W., Yi, N., He, W., Lu, P.,
Li, B., Yang, N., Wang, D., Xue, Z., Zhang, P., Fan, G., Zhu, X. A novel
immunodeficient rat model supports human lung cancer xenografts.
PMID- 29944448
TI - Comparison between the impacts of two different modes of salicylic acid
application on tomato (Solanum lycopersicum) responses to salinity.
AB - Exogenous application of salicylic acid may improve tolerance to salinity. To
investigate whether exogenous salicylic acid application had similar protective
effects when applied as a priming agent or concomitantly with NaCl, tomato
seedlings primed or not with 10 uM salicylic acid were further treated with 125
mM NaCl, 10 uM salicylic acid or combined treatments. Both priming and
concomitant application of salicylic acid increased plant growth of salt-stressed
plants but their positive impact was not additive. The endogenous salicylic acid
concentration increased in the leaves after concomitant application but not in
response to priming, suggesting that salicylic acid accumulated during priming
was metabolized subsequently. Priming increased Na+ and K+ accumulation in leaves
of salt-treated plants while concomitant application had no impact on shoot Na+
and K+ accumulation. Both priming and concomitant salicylic acid decreased
osmotic potential values in salt-treated plants. Carbon isotope discrimination
showed that combination of both salicylic acid application methods were required
to maintain a good water use efficiency in salt-treated plants. Our work
demonstrated that both procedures of salicylic acid application have positive
impact on salt resistance but that the underlying properties sustaining these
adaptations differ according to application methods.
PMID- 29944449
TI - Is the diurnal variation in muscle force output detected/detectable when multi
joint movements are analysed using the musclelab force-velocity encoder?
AB - We have investigated the magnitude of diurnal variation in back squat and bench
press performance using the MuscleLab force velocity transducer. Thirty
resistance-trained males (mean +/- SD: age 21.7 +/- 1.4 years; body mass 80.5 +/-
4.5 kg; height 1.79 +/- 0.06 m) underwent two sessions at different times of day:
morning (M, 07:30 h) and evening (E, 17:30 h). Each session included a period
when rectal temperature (Trec) was measured at rest, a 5-min standardized 150 W
warm-up on a cycle ergometer, then defined programme of bench press (at 20, 40
and 60 kg) and back squat (at 30, 50 and 70 kg) exercises. A linear encoder was
attached to an Olympic bar used for the exercises and average force (AF), peak
velocity (PV) and time-to-peak velocity (tPV) were measured (MuscleLab software;
MuscleLab Technology, Langesund, Norway) during the concentric phase of the
movements. Values for Trec at rest were higher in the evening compared to morning
values (0.48 degrees C, P < 0.0005). Daily variations were apparent for both
bench press and back squat performance for AF (1.9 and 2.5%), PV (8.3 and 12.7%)
and tPV (-16.6 and -9.8%; where a negative number indicates a decrease in the
variable from morning to evening). There was a main effect for load where AF and
tPV increased and PV decreased from the lightest load to the heaviest for both
bench press and back squat (47.1 and 80.2%; 31.7 and 57.7%; -42.1 and -73.9%; P <
0.0005 where a negative number indicates a decrease in the variable with
increasing load). An interaction was found only for tPV, such that the tPV occurs
earlier in the evening than the morning at the highest loads (60 and 70 kg) for
both bench press and back squat, respectively (mean difference of 0.32 and 0.62
s). In summary, diurnal variation in back squat and bench press was shown; and
the tPV in complex multi-joint movements occurs earlier during the concentric
phase of exercise when back squat or bench press is performed in the evening
compared to the morning. This difference can be detected using a low cost,
portable and widely available commercial instrument and enables translation of
past laboratory/tightly controlled experimental research in to main-stream
coaching practice.
PMID- 29944450
TI - Induced ovule-to-flower switch by interfering with SlIMA activity in tomato.
AB - The INHIBITOR OF MERISTEM ACTIVITY in tomato (SlIMA) and MINI ZINC FINGER 2 in
Arabidopsis (AtMIF2), two members of the MINI ZINC FINGER family (MIF), are
involved in the regulation of flower and ovule development. MIF proteins possess
a unique non-canonical zinc-finger domain that confers the capacity to interact
with other protein partners. The characterization of SlIMA and AtMIF2 gain- and
loss-of-function transgenic lines in Solanum lycopersicum and Arabidopsis
thaliana respectively, allowed the demonstration of their conserved functional
role in the termination of floral stem cell maintenance. During early floral
development, the expression of SlIMA and AtMIF2 is induced by the MADS-Box
transcription factor AGAMOUS (AG). Then, SlIMA or AtMIF2 protein recruits the
C2H2 zinc finger KNUCKLES (KNU), in a transcriptional repressor complex together
with TOPLESS (TPL) and HISTONE DEACETYLASE19 (HDA19). This complex binds to the
WUSCHEL (WUS) locus leading to its repression. To further characterize the role
of these interactions in flower development, we have investigated the effects of
a dominant negative form of SlIMA, SlIMAch that leads to spectacular phenotypes,
including ovule conversion into a floral meristem.
PMID- 29944452
TI - Differences in determinants of aerobic and muscle strengthening physical activity
among college students: a reasoned action approach.
AB - While there is a concerted effort to promote physical activity (PA) across United
States government and non-governmental organizations, interventions typically
focus on aerobic forms of PA, leaving out muscle strengthening PA. The purpose of
this study was to operationalize the Reasoned Action Approach (RAA) to explain
theory-based correlates of aerobic and muscle strengthening PA, which can provide
targets for future public health interventions. Theory-based correlates of both
PA behaviors were evaluated using logistic regression analyses, and intentions
predicted a significant amount of aerobic PA (14.9%) and muscle strengthening PA
(30.7%). Theory-based correlates of intentions to both PA behaviors were
evaluated using linear regression analyses, and attitudes, perceived norms, and
perceived behavioral control predicted a significant amount for aerobic PA (46.2%
to 55.8%) and for muscle strengthening PA (53.9% to 59.8%). Finally, theory-based
correlates of attitudes, injunctive norms, descriptive norms and perceived
behavioral control were evaluated using salient beliefs, derived from an
elicitation study. Results suggest that the RAA is a robust framework for
predicting both types of PA behaviors. Belief-based measures also provides
guidance for future public health promotion interventions and health
communication strategies.
PMID- 29944451
TI - Development of sugar beet leaves: contents of hormones, localization of abscisic
acid, and the level of products of photosynthesis.
AB - The level of hormones in the tissues of sugar beet leaves of different age in
parallel with their growth and metabolic activity was assayed; the latter was
analyzed, measuring the contents of sugars and N-containing compounds, and the
activities of Rubisco and proteases. The highest auxin and ABA concentration was
detected in the actively growing upper leaf, while high level of cytokinins was
maintained in the middle and upper leaves characterized by intensive
photosynthesis. Leaf senescence being manifested in decline of chlorophyll
content, decrease of photosynthesis and activation of proteolysis was accompanied
by a decline in concentration of cytokinins. Glucose level gradually increased
from upper (younger) to a lower (elder) leaves; this was accompanied with the
signs of senescence on the background of decreased cytokinins level. Immuno
histochemical technique revealed increased level of abscisic acid in phloem
parenchyma of the lowest leaf. The results suggest a possible involvement of
auxins in maintaining leaf growth, an implication of decreased cytokinins level
in the hypothesized induction of senescence by glucose, and a participation of
abscisic acid in the active loading of metabolites into the phloem of senescing
leaf.
PMID- 29944453
TI - Relationship between immune cells and alcohol dependents and controls: what about
the lymphocyte-related ratios?
PMID- 29944454
TI - Inferior Turbinate Swing Technique: A Novel Surgical Route to Approach Maxillary
Sinus Area Pathology.
AB - The inferior turbinate is an important structure for maintenance of adequate
physiologic function within the nasal cavity. However, it hampers access to
lesions involving maxillary sinus areas, including postoperative mucocele or
benign tumor, and acts as an inferior limit to widening the natural ostium of a
maxillary sinus. Here, we introduce a novel technique, interior turbinate swing,
to facilitate entry to the inferior meatus or maxillary sinus while maintaining
integrity of the inferior turbinate. In this technique, the anterior part of
inferior turbinate is cut with sharp scissors, rotated posteriorly, and held in
the nasopharynx. The inferior turbinate swing technique was employed in 38
subjects, and no patients exhibited recurrence of the causative disease without
complication. Therefore, we may conclude that the inferior turbinate swing
technique is a simple, effective, and safe treatment option for the management of
postoperative mucocele, maxillary sinusitis with narrow inlet, or benign tumors.
PMID- 29944455
TI - Exploring the metabolic variation between domesticated and wild tetraploid wheat
genotypes in response to corn leaf aphid infestation.
AB - Infestation of Triticum (wheat) plants by their pest Rhopalosiphum maidis (corn
leaf aphid) causes severe vegetative damage. Despite the agro-economic importance
of wheat, the metabolic diversity of Triticum turgidum (tetraploid wheat) in
response to aphid attack has not been sufficiently addressed. In this study, we
compared the metabolic diversity of two tetraploid wheat genotypes, domesticated
and wild emmer. The plants were grown in a control growth room and infested with
aphids for 96 h. Our untargeted metabolic analysis performed on plants with and
without aphids revealed massive differences between the two genotypes. The
targeted metabolic analysis highlighted the differences in the biosynthesis of
phytohormones. The aphid progeny was lower in the cultivated durum wheat than in
the wild emmer wheat. Overall, these observations emphasize the potential of
using the natural diversity of wheat species to better understand the metabolic
responses to pest damage.
PMID- 29944456
TI - Estimation of a Preference-Based Summary Score for the Patient-Reported Outcomes
Measurement Information System: The PROMIS(r)-Preference (PROPr) Scoring System.
AB - BACKGROUND: Health-related quality of life (HRQL) preference-based scores are
used to assess the health of populations and patients and for cost-effectiveness
analyses. The National Institutes of Health Patient-Reported Outcomes Measurement
Information System (PROMIS(r)) consists of patient-reported outcome measures
developed using item response theory. PROMIS is in need of a direct preference
based scoring system for assigning values to health states. OBJECTIVE: To produce
societal preference-based scores for 7 PROMIS domains: Cognitive Function
Abilities, Depression, Fatigue, Pain Interference, Physical Function, Sleep
Disturbance, and Ability to Participate in Social Roles and Activities. SETTING:
Online survey of a US nationally representative sample ( n = 983). METHODS:
Preferences for PROMIS health states were elicited with the standard gamble to
obtain both single-attribute scoring functions for each of the 7 PROMIS domains
and a multiplicative multiattribute utility (scoring) function. RESULTS: The 7
single-attribute scoring functions were fit using isotonic regression with linear
interpolation. The multiplicative multiattribute summary function estimates
utilities for PROMIS multiattribute health states on a scale where 0 is the
utility of being dead and 1 the utility of "full health." The lowest possible
score is -0.022 (for a state viewed as worse than dead), and the highest possible
score is 1. LIMITATIONS: The online survey systematically excludes some
subgroups, such as the visually impaired and illiterate. CONCLUSIONS: A generic
societal preference-based scoring system is now available for all studies using
these 7 PROMIS health domains.
PMID- 29944457
TI - Current methods for tumor-associated macrophages investigation.
AB - Oncoimmunology is a rapidly growing field, focusing both on studying of the
interaction of immune factors with tumor cells and also on the development of new
therapies. In this regard, immunotherapy is increasingly used clinically.
Although tumorigenesis is generally seen as an autonomous process involving
genetically transformed cancer cells, it is increasingly recognized that tumor
environment is an essential factor that modulates both tumor progression and
resistance to therapy. Tumor-associated immune cells, and in particular
macrophages, are of particular importance in all stages of the tumorigenesis
process and are also a clinical prognostic marker. From quantification of a
single analyte in a given sample to complex platforms comprising multiple
techniques, several methods for investigation of the dynamic balance and
interaction between tumor-associated macrophages (TAMs) and tumor cells are
available. This review presents the techniques carried out currently for
investigation of TAMs functions, interactions, and modulation both at
translational and transcriptional levels - ELISA and Multiplex assays, flow
cytometry, immunohistochemistry, DNA microarray - as essential steps not only for
research purposes but also for predicting the therapeutic efficiency and patient
survival.
PMID- 29944458
TI - Can international elite sport success trickle down to mass sport participation?
Evidence from Danish team handball.
AB - Many scholars do not find evidence of a trickle-down effect from elite sport
success to mass sport participation. Contrary to what is assumed by the trickle
down effect "theorem", successful elite sportspeople do not seem to inspire
amateurs to take up sport themselves. However, recent studies present evidence
that elite sport can have an influence. In this article, we apply regression
models on time series data from one of the most successful Danish sports, team
handball. Our findings are mixed, but lean towards supporting scholars who argue
that trickle-down effects are not necessarily an inherent part of international
sporting success. Further studies should examine more sports to identify where
trickle-down effects occur and why.
PMID- 29944459
TI - Role of TAF15b in transcriptional regulation of autonomous pathway for flowering.
AB - The autonomous pathway promotes flowering by repressing a major flowering
repressor, FLOWERING LOCUS C (FLC). Approximately 30 genes are involved in this
pathway, and several of them are related to RNA processing; however, the
molecular basis of the transcriptional regulation of FLC is yet to be understood.
Recently, we discovered a new autonomous pathway gene, TATA-binding protein
associated factor 15b (TAF15b), which has a RNA recognition motif (RRM) and
represses the level of FLC transcripts. TAF15b regulates the expression of FLC by
directly interacting with RNA polymerase II (Pol II) at the transcription start
sites on both the sense and antisense strands of the FLC locus. In addition to
the transcriptional regulation in the nucleus, TAF15b accumulates in processing
bodies (p-bodies), which are cytoplasmic RNA granules involved in translational
repression, during heat stress. Here we discuss the implications of our findings
and suggest a dual role of TAF15b in both transcriptional and translational
regulation.
PMID- 29944460
TI - Stage II Oral Tongue Cancer: Survival Impact of Adjuvant Radiation Based on Depth
of Invasion.
AB - Objective To determine if adjuvant radiation therapy for patients with pT2N0 oral
cavity tongue cancer affects overall survival. Study Design Retrospective cohort
study. Setting National Cancer Database. Subjects and Methods Cases diagnosed
between 2004 and 2013 with pathologic stage pT2N0 oral cavity tongue cancer with
negative surgical margins were extracted from the National Cancer Database. Data
were stratified by treatment received, including surgery only and surgery +
postoperative radiation therapy. Univariate analysis was performed with a 2
sample t test, chi-square test, or Fisher exact test and log-rank test, while
multivariate analysis was performed with Cox regression models adjusted for
individual variables as well as a propensity score. Results A total of 934
patients were included in the study, with 27.5% of patients receiving surgery
with postoperative radiation therapy (n = 257). In univariate analysis, there was
no significant difference in 3-year overall survival between the patient groups (
P = .473). In multivariate analysis, there was no significant difference in
survival between the treatment groups, with adjuvant radiation therapy having a
hazard ratio of 0.93 (95% CI, 0.60-1.44; P = .748). Regarding tumors with a depth
of invasion >5 mm, there was no survival benefit for the patients who received
postoperative radiation therapy as compared with those who received surgery alone
(hazard ratio = 0.93; 95% CI, 0.57-1.53; P = .769). Conclusion An overall
survival benefit was not demonstrated for patients who received postoperative
radiation therapy versus surgery alone for pT2N0 oral cavity tongue cancer,
irrespective of depth of tumor invasion.
PMID- 29944461
TI - Modeling Cell and Tumor-Metastasis Dosimetry with the Particle and Heavy Ion
Transport Code System (PHITS) Software for Targeted Alpha-Particle Radionuclide
Therapy.
AB - The use of targeted radionuclide therapy for cancer is on the rise. While beta
particle-emitting radionuclides have been extensively explored for targeted
radionuclide therapy, alpha-particle-emitting radionuclides are emerging as
effective alternatives. In this context, fundamental understanding of the
interactions and dosimetry of these emitted particles with cells in the tumor
microenvironment is critical to ascertaining the potential of alpha-particle
emitting radionuclides. One important parameter that can be used to assess these
metrics is the S-value. In this study, we characterized several alpha-particle
emitting radionuclides (and their associated radionuclide progeny) regarding S
values in the cellular and tumor-metastasis environments. The Particle and Heavy
Ion Transport code System (PHITS) was used to obtain S-values via Monte Carlo
simulation for cell and tumor metastasis resulting from interactions with the
alpha-particle-emitting radionuclides, lead-212 (212Pb), actinium-225 (225Ac) and
bismuth-213 (213Bi); these values were compared to the beta-particle-emitting
radionuclides yttrium-90 (90Y) and lutetium-177 (177Lu) and an Auger-electron
emitting radionuclide indium-111 (111In). The effect of cellular internalization
on S-value was explored at increasing degree of internalization for each
radionuclide. This aspect of S-value determination was further explored in a cell
line-specific fashion for six different cancer cell lines based on the cell
dimensions obtained by confocal microscopy. S-values from PHITS were in good
agreement with MIRDcell S-values (cellular S-values) and the values found by
Hindie et al. (tumor S-values). In the cellular model, 212Pb and 213Bi decay
series produced S-values that were 50- to 120-fold higher than 177Lu, while 225Ac
decay series analysis suggested S-values that were 240- to 520-fold higher than
177Lu. S-values arising with 100% cellular internalization were two- to sixfold
higher for the nucleus when compared to 0% internalization. The tumor dosimetry
model defines the relative merit of radionuclides and suggests alpha particles
may be effective for large tumors as well as small tumor metastases. These
results from PHITS modeling substantiate emerging evidence that alpha-particle
emitting radionuclides may be an effective alternative to beta-particle-emitting
radionuclides for targeted radionuclide therapy due to preferred dose-deposition
profiles in the cellular and tumor metastasis context. These results further
suggest that internalization of alpha-particle-emitting radionuclides via
radiolabeled ligands may increase the relative biological effectiveness of
radiotherapeutics.
PMID- 29944462
TI - Personalized design of ankle-foot prosthesis based on computer modeling of
amputee locomotion.
AB - This study proposes a computer modeling approach to find the optimal damping
coefficients of the viscoelastic ankle-foot prostheses for each specific amputee.
A two-dimensional locomotion model was developed for a transtibial amputee and
personalized using his body measures and the reference gait pattern of an
equivalent able-bodied subject. By employing the forward dynamic simulation, the
amputee's locomotion was synthesized for different prosthetic settings to find
the optimal damping coefficients, based on a kinematics and a total work cost
function. Results indicated a good agreement between the model predictions and
the experimental observations.
PMID- 29944463
TI - Effects of a long-term smartphone-based self-monitoring intervention in patients
with lipid metabolism disorders.
AB - The majority of lipid metabolism disorders can be managed well if patients adhere
to their therapies. Self-monitoring can drive adherence with regards to
medication intake, physical activities, and nutrition. Technical devices like
smartphones can further support its users to achieve health-related goals. In a
clinical trial, 100 patients with lipid metabolism disorders were asked to use a
smartphone application over a duration of 12 months. Users of this app could set
reminders to keep track of their medication and other disease-related variables,
such as weight and cholesterol. More than half of all patients that started to
use the app continued to use the app over the full 12 months. However, 43% of the
patients that were asked to use the app stated that they never started to use the
app. The reasons cited were lack of time, health problems, lack of motivation,
and technical problems. The number of patients with high medication adherence
increased significantly due to the use of the app. Health apps might benefit
patients by enabling them to better manage chronic diseases, but successful
digital health concepts will need to address efficient onboarding as well as long
term motivation.
PMID- 29944464
TI - Anaeromyces contortus, sp. nov., a new anaerobic gut fungal species
(Neocallimastigomycota) isolated from the feces of cow and goat.
AB - Ten different anaerobic gut fungal strains were isolated from fecal samples of
cow and goat in Oklahoma, USA. The isolates displayed polycentric thalli,
uniflagellated zoospores, and sausage-shaped hyphal constrictions, all
characteristic of the genus Anaeromyces, and lobed or appressorium-like
structures on the hyphae, previously reported in Anaeromyces elegans but not in
A. mucronatus or A. robustus. Further, the strains exhibited highly coiled and
entangled hyphae previously unreported in the Neocallimastigomycota, but
resembling fungal traps previously observed in multiple nematophagous fungi.
Scanning electron micrographs of isolates grown on switchgrass showed entrapment
of plant material by the hyphal coils and the penetration of plant fibers at
various sites by the appressorium-like structures. Molecular analysis based on
sequences of both partial nuc rDNA ITS1 spacer region and the D1-D2 domains of
the nuc28S rDNA confirmed the classification of all isolates in Anaeromyces and
confirmed their phylogenetic distance from the available A. mucronatus and A.
robustus sequences. On the basis of morphological and phylogenetic distinctions,
we conclude that these strains represent a new Anaeromyces species, for which A.
contortus is proposed.
PMID- 29944466
TI - SIT LESS: A prototype home-based system for monitoring older adults sedentary
behavior.
AB - This paper presents the overall design of a prototype home-based system aimed to
reduce sedentary behavior of older adults. Quantitative performance indicators
were developed to measure the sedentary behavior and daily activities of an older
adult. The sedentary behavior is monitored by identifying individual positions
(standing, sitting, and lying) within the field of view of a Microsoft Kinect
sensor, using a custom designed algorithm. The physical activity of the older
adult when outside the field of view of the Microsoft Kinect sensor is monitored
by counting the number of steps using a Fitbit Charge HR watch, which the older
adult is equipped with. A user interface was developed on a PC platform to
interact with the older adult. The user interface is automatically operated and
includes several modules. It displays the activity level, and provides feedbacks,
alerts, and reminders to reduce sedentary behavior. Evaluations using a mixed
methods approach that included a focus group, interviews, and observations were
conducted to examine the integrated system, evaluate the users' experience with
the system, and compare different types of feedbacks and alerts. The analyses
indicated the feasibility of the proposed SIT LESS system along with
recommendations for improving the system in future research.
PMID- 29944465
TI - Being mothers and fathers of a child with type 1 diabetes aged 1 to 7 years: a
phenomenological study of parents' experiences.
AB - PURPOSE: The diagnosis of diabetes in pre-school children poses a number of
unique challenges related to everyday responsibility, and the continuous need for
supervision and caregiving. This may affect both the child's and the parents'
perceived burden caused by the condition. The aim of the study was to explore the
lived experience of being mothers and fathers of a child with type 1 diabetes
aged 1 to 7 years. METHODS: The study is rooted in an interpretive
phenomenological methodology as described by van Manen. In-depth interviews were
carried out to collect data. FINDINGS: We were able to identify one essential
theme across the interviews: Striving to live an ordinary family life, yet
feeling and living very differently-with interrelated sub-themes: A life-changing
situation, Always on guard, and Struggling to let go. CONCLUSION: Parents
described a profoundly changed situation, and they were indeed striving to live
like a "normal" family. They were in need of support from health care
professionals at the outpatient clinic, not only support and supervision in
regard to practical tasks, but also concerning handling a changed life situation
and emotional reactions, especially in the first year after diagnosis.
PMID- 29944467
TI - Effect of integrated yoga on anti-psychotic induced side effects and cognitive
functions in patients suffering from schizophrenia.
AB - Background Twenty one (12 females) subjects, diagnosed with schizophrenia by a
psychiatrist using ICD-10, in the ages 52.87 + 9.5 years and suffering since 24.0
+/- 3.05 years were recruited into the study from a schizophrenia rehabilitation
center in Bengaluru. Methods All subjects were taking anti-psychotic medications
and were in stable state for more than a month. Psychiatric medications were kept
constant during the study period. Assessments were done at three points of time:
(1) baseline, (2) after one month of usual routine (pre) and (3) after five
months of validated Integrated Yoga (IY) intervention (post). Validated 1 h Yoga
module (consisting of asanas, pranayama, relaxation techniques and chantings) was
practiced for 5 months, five sessions per week. Antipsychotic-induced side
effects were assessed using Simpson Angus Scale (SAS) and Udvalg for Kliniske
Undersogelser (UKU) side effect rating scale. Cognitive functions (using Trail
making Test A and B), clinical symptoms and anthropometry were assessed as
secondary variables. Comparisons between "pre" and "post" data was done using
paired samples t-tests after subtracting baseline scores from them respectively.
Results At the end of five months, significant reduction in drug-induced
Parkinsonian symptoms (SAS score; p=0.001) and 38 items of UKU scale was observed
along with significant improvement in processing speed, executive functions and
negative symptoms of schizophrenia patients. No side effects of Yoga were
reported. Conclusions The present study provides preliminary evidence for
usefulness of Integrated Yoga intervention in managing anti-psychotic-induced
side effects.
PMID- 29944468
TI - Induction of neutrophil apoptosis by a Bcl-2 inhibitor reduces particulate matter
induced lung inflammation.
AB - BackgroundEnvironmental particulate matter exposure can cause various respiratory
problems including aggravated asthma, decreased lung function and increased
respiratory symptoms. However, the molecular mechanisms underlying PM-induced
lung inflammation are incompletely understood. Effective therapeutic strategies
are required.ResultsA mouse model of particulate matter-induced lung inflammation
was used to identify the pathology and the molecular mechanisms for particulate
matter-induced lung inflammation. The mouse model revealed that particulate
matter induced neutrophil-dominated lung inflammation. Neutrophils derived from
particulate matter-instilled mice showed decreased apoptosis and elevated Bcl-2
expression. Further studies in vav-Bcl-2 transgenic mice made it clear that Bcl-2
overexpression caused a marked increase in neutrophils in bronchoalveolar lavage
fluid. Furthermore, we found that the Bcl-2 inhibitor ABT-199 reduced particulate
matter-induced lung inflammation, and induced apoptosis of neutrophils in
particulate matter-induced lung inflammation mice model.ConclusionsParticulate
matter-induced lung inflammation is mediated in part by inhibition of apoptosis
of inflammatory cells. Bcl-2 is responsible for the reduced apoptosis of
inflammatory cells in particulate matter-induced lung inflammation. The Bcl-2
selective inhibitor ABT-199 reduces particulate matter-induced lung inflammation
by inducing the apoptosis of neutrophils and might be a promising drug for the
treatment of particulate matter-induced lung inflammation.
PMID- 29944469
TI - Carbon nanotube sponges as tunable materials for electromagnetic applications.
AB - The microwave conductivity and permittivity of both single-walled and multi
walled carbon nanotube (SWCNT and MWCNT) sponges were measured while compressing
the samples. Compression leads to a huge variation of the absorptance,
reflectance, and transmittance of the samples. The dependence of the microwave
conductivity on the sponge density follows a power-law relation with exponents
1.7 +/- 0.1 and 2.0 +/- 0.2 for MWCNT and SWCNT sponges, respectively. These
exponents can be decreased slightly by the addition of a non-conducting component
which partly electrically separates adjacent tubes within the samples. The
conductivity of MWCNT sponge was measured in the terahertz range while heating in
air from 300 to 513 K and it increased due to an increase of a number of
conducting channels in MWCNTs.
PMID- 29944470
TI - Reversal of docetaxel resistance in prostate cancer by Notch signaling
inhibition.
AB - Acquired docetaxel (Doc) resistance in hormone-refractory prostate cancer (HRPC)
remains an ongoing clinical challenge, resulting in failed chemotherapy and tumor
recurrence. However, the mechanism of Doc-resistance development in prostate
cancer cells is still unclear. Here, we observed a subpopulation of prostate
cancer cells, in both Doc-resistant cell lines and the tumors of patients with
HRPC, which show stem cell markers and greater tumorigenic potential. Those stem
like prostate cancer cells show high expression of ABCB1, which encodes multidrug
resistance-related protein P-glycoprotein, leading to the Doc-resistance in
prostate cancer. Moreover, we found that Notch signaling pathway activation in
Doc-resistant cell lines and tumor tissues of patients with HRPC correlated with
tumorigenicity and the development of Doc resistance. Here, we revealed that a
combination of Doc and a Notch signaling inhibitor overcomes Doc resistance and
increases the survival of mice with Doc-resistant xenografts. Therefore,
targeting the Notch signaling pathway may be a promising strategy to overcome the
Doc-resistant cancer in the clinic.
PMID- 29944471
TI - Prostatic Adenocarcinoma With Focal Pleomorphic Giant Cell Features: A Series of
30 Cases.
AB - Prostatic adenocarcinoma with focal pleomorphic giant cell features is rare with
the only prior series consisting of 6 cases. From 2005 to 2018, we identified 29
cases from our consult service and 1 case from our own institution. Men ranged in
age from 39 to 90 years (median=75.5). Diagnostic specimens consisted of needle
biopsies (n=13); transurethral resections (n=7), urethral/bladder biopsies (n=8),
radical prostatectomy (n=1), and orchiectomy (n=1). In all cases, there was usual
acinar prostatic adenocarcinoma, where the highest grade in all cases was Gleason
score 9 to 10 (Grade Group 5). On average, 68% of the involved cores had cancer
with a maximum percent of cancer averaging 55%; on average, transurethral
resections had 85% of the area involved by cancer. Areas of cancer showing
pleomorphic giant cell features were focal (<5%). Two of the needle biopsies
showed extraprostatic extension. The radical prostatectomy had seminal vesicle
invasion and positive margins with lymphovascular invasion. Prostatic
adenocarcinoma with focal pleomorphic giant cell features is always accompanied
by extensive usual acinar prostate adenocarcinoma where the highest grade in all
cases was Gleason score 9 to 10 (Grade Group 5). Although the pleomorphic
component is focal, it can mimic urothelial carcinoma. IHC can be misleading as
PSA staining is often negative or focal in both the pleomorphic and usual
prostatic adenocarcinoma components. NKX3.1 is the most sensitive prostate
marker, but was still focal in 1 usual prostatic adenocarcinoma and negative in 2
pleomorphic components. Prostatic adenocarcinoma with focal pleomorphic giant
cell features has a dismal prognosis. In men with no prior diagnosis of prostate
adenocarcinoma and >1-year follow-up, 7/19 (37%) were dead at a median of 8
months after diagnosis. Of the 7 men with a prior history of prostate
adenocarcinoma, 4/7 (57%) were dead at a median of 7 months after diagnosis of
recurrent prostate adenocarcinoma with pleomorphic giant cell features.
PMID- 29944472
TI - Evaluating outcomes of mother-infant pairs using dolutegravir for HIV treatment
during pregnancy.
AB - OBJECTIVES: Dolutegravir (DTG), a second-generation integrase inhibitor, is an
effective treatment for HIV but its safety and efficacy are not well established
in pregnancy. Here, we assess maternal and infant outcomes of mother-infant pairs
using DTG-containing regimens during pregnancy. METHODS: We performed a
retrospective cohort analysis of pregnant women with HIV on DTG from two urban
clinics in the United States, 2015-2018. Maternal outcomes included viral
suppression (viral load of <20 copies/ml prior to delivery), development of
resistance, and tolerability to DTG. Infant outcomes included preterm delivery
(birth at <37 weeks), small for gestational age (SGA, weight <10th percentile),
infant HIV status at birth, birth defect(s), and Appearance, Pulse, Grimace,
Activity, Respiration (APGAR) scores. We performed a trend analysis to assess DTG
use over time. RESULTS: A total of 66 women used DTG during pregnancy and the
proportion on DTG increased each year: in 2015, 8% (5/60) of women were on DTG,
versus 22% (15/67) in 2016, 42% (30/71) in 2017, and 59% (16/27) in 2018 (P <
0.05). Among women who delivered (n = 57), 77.2% were undetectable at delivery.
There were no drug resistance and no reported side effects during pregnancy.
Infants had a mean APGAR score of 8 (SD 1.5) at 1 min and 9 (SD 0.8) at 5 min;
31.6% were born prematurely and 15.8% were SGA, and 2 infants had a birth defect.
No cases of HIV transmission occurred. CONCLUSION: Our findings suggest that DTG
can be an effective treatment during pregnancy. Infant outcomes (preterm
deliveries and birth defects) need to be investigated in larger studies.
PMID- 29944473
TI - Cutaneous Metastasis of Choriocarcinoma in 2 Male Patients: A Rare Presentation
of an Aggressive Malignancy That Dermatopathologists Must Recognize.
AB - Testicular choriocarcinoma needs to be considered in the differential diagnosis
of cutaneous metastases in young adult men because of its propensity for early
hematogenous dissemination. Furthermore, the diagnosis may not be suspected in
many cases in which there is clinically no testicular enlargement. This highly
aggressive germ cell tumor typically metastasizes to the liver, lungs, and brain.
Skin metastasis is exceedingly rare with only 22 cases previously reported in the
world literature. We herein report 2 additional cases: a 25-year-old man and a 32
year-old man, both of whom were treated for mixed germ cell tumors and developed
multiple cutaneous metastases to the head.
PMID- 29944474
TI - Relationships Between Cognitive Complaints and Quality of Life in Older Adults
With Mild Cognitive Impairment, Mild Alzheimer Disease Dementia, and Normal
Cognition.
AB - PURPOSE: To examine in persons with varying degrees of cognitive impairment the
relationship between self-reports of cognitive complaints and quality of life
(QOL). METHODS: Older adults (n=259) with normal cognition, mild cognitive
impairment (MCI), and mild stage Alzheimer disease (AD) dementia completed tests
of cognition and self-report questionnaires about QOL and 3 kinds of cognitive
complaints: cognitive difficulties, distress from cognitive difficulties, and
believing you had more memory problems than most people. Bivariate,
multivariable, and multivariate regression analyses assessed relationships
between domains of QOL and each cognitive complaint. RESULTS: Bivariate and
multivariable analyses controlling for severity of cognitive and functional
impairment found that cognitive complaints were related to relatively lower
quality of daily life (QOL-AD, Dementia Quality of Life Scale), greater
depression (GDS), more anxiety (BAI), higher perceived stress (PSS), and lower
general mental well-being (SF-12 MCS). DISCUSSION: Cognitive complaints have
robust associations with QOL. These findings have implications for AD prevention
trials and management of clinical populations.
PMID- 29944475
TI - Alzheimer Disease Clinical Trial Recruitment: Does Participation in a Brief
Cognitive Screen at a Community Health Fair Promote Research Engagement?
AB - BACKGROUND: Slow participant recruitment impedes Alzheimer disease research
progress. Although research suggests that direct involvement with potential
participants supports enrollment, strategies for how best to engage potential
participants are still unclear. PURPOSE: This study explores whether community
health fair (HF) attendees who engage in a brief cognitive screen (BCS) are more
likely to enroll in research than attendees who do not complete a BCS. SUBJECTS:
A total of 483 HF attendees. METHODS: Attendees were tracked for a 1-year period
to ascertain research involvement. RESULTS: In total, 364 attendees expressed
interest in research and 126 completed a BCS. Over the follow-up period, 21
individuals prescreened as eligible and 19 enrolled in an investigational study.
Among all HF attendees, BCS completers had a 2.5-fold increase in subsequently
prescreening as eligible as compared with non-BCS completers. However, when
limited only to participants who stated an interest in research, this difference
was no longer significant. CONCLUSIONS: Completing a BCS at a community event may
be an indicator of future research engagement, but for those already interested
in participation, the BCS may be a poor indicator of future involvement. The BCS
may also reduce anxiety and stigma around memory evaluation, which may translate
into research engagement in the future.
PMID- 29944476
TI - Outcomes after culprit-only percutaneous coronary intervention for multivessel
disease during ST-segment elevation myocardial infarction: a comparison of
registry and clinical trial outcomes.
AB - BACKGROUND: The PRAMI and CvLPRIT trials support preventive percutaneous coronary
intervention (PCI) for multivessel coronary disease found during ST-segment
elevation myocardial infarction (STEMI). We assess our real-world experience of
the management of multivessel disease identified during primary PCI (PPCI) in a
large UK regional centre. PATIENTS AND METHODS: All STEMI patients who underwent
culprit-only PPCI during the study period (August 2011 to August 2013) were
retrospectively assessed for eligibility to each trial. The two resulting groups
were designated as the 'observational' cohorts. Primary outcomes were then
determined and compared with the culprit-only revascularisation cohorts from the
respective published randomized controlled trials (RCTs). RESULTS: A total of
1143 consecutive cases were presented during the study period. Of these, 343
would have been suitable for inclusion to PRAMI and were included in the
'observational PRAMI' cohort; 196 patients were included in the 'observational
CvLPRIT' cohort.The 'observational PRAMI' cohort experienced fewer primary
outcome events (13.1 vs. 22.9%), cardiac deaths (0.6 vs. 4.3%) and nonfatal
myocardial infarctions (3.5 vs. 8.7%) than the culprit-only PCI PRAMI cohort
(n=231); there were significantly more diabetics (P=0.022) and anterior STEMI
initial presentations in the culprit-only PCI PRAMI cohort. Primary outcomes were
comparable to those of the preventive PCI PRAMI cohort.The 'observational
CvLPRIT' cohort showed no significant difference in primary outcomes over 12
months (16.8 vs. 21.2%), but significantly lower all-cause mortality (2 vs. 6.9%)
than the culprit-only PCI CvPLRIT cohort (n=146). The 30-day event rates were
similar to the preventive PCI arm; the 12-month events were better than the
nonpreventive, but not as good as the preventive RCT cohorts. CONCLUSION:
Outcomes from culprit-only primary PCI for multivessel disease in patients
selected by the RCT criteria from an all-comers population representing real-life
experience are better than those published in the two main RCTs. The RCTs may
have selected a high-risk population for study exaggerating the benefits of
preventive PCI.
PMID- 29944477
TI - Relationship With the Father of the Baby and Perceived Stress Among Black Women.
AB - OBJECTIVE: The purpose of this study was to examine whether the relationship with
the father of the baby was related to psychological stress among Black women.
METHODS: This is a secondary analysis of data derived from a retrospective cohort
study of 1,410 Black new mothers participating in the Life-course Influences on
Fetal Environments (LIFE) study conducted in the Detroit Metropolitan area. Data
were obtained from maternal interview and medical records abstraction. Perceived
stress was measured by the Cohen's Perceived Stress Scale. The mother's
relationship with the father of the baby before and after pregnancy was measured
using two questions. RESULTS: Women who reported sometimes close/sometimes
distant relationship with the father of the baby prior to pregnancy had higher
levels of perceived stress compared with women who reported close relationship
with the father of the baby prior to pregnancy (38.73 and 35.10, respectively, p
< .001). Women who reported current distant relationship (38.82 and 34.45,
respectively, p < .001) and sometimes close/sometimes distant relationship (38.83
and 34.45, respectively, p < .001) reported higher levels of perceived stress
compared with women who had current close relationship with the father of the
baby. CLINICAL IMPLICATIONS: Women who reported to have a close relationship with
the father of the baby before and during the pregnancy reported lower levels of
stress compared with women with a distant relationship with the father of the
baby. Nurses should assess women's relationship with the father of the baby and
their levels of stress.
PMID- 29944478
TI - Psychosocial Factors and Preterm Birth Among Black Mothers and Fathers.
AB - OBJECTIVE: Black women are more likely to live in disadvantaged neighborhoods and
experience racial discrimination and psychological stress compared with White
women. These factors have been related to preterm birth (PTB). However, research
is limited on the associations of disadvantaged neighborhoods, racial
discrimination, and psychological stress among expectant Black fathers and PTB.
This review focuses on what is known about psychosocial factors in relation to
PTB among Black parents. METHODS: The Scopus database was used to search for
studies using keywords of adverse childhood experiences, neighborhood
environment, racial discrimination, psychological stress, depressive
symptoms/depression, coping, locus of control, social support, and mother-father
relationship. Each of these keywords was combined with the term preterm birth.
This review focused on the associations of these psychosocial factors collected
during the prenatal period and risk for PTB. However, due to lack of data for
some of these factors during the prenatal period, studies conducted in the
immediate period after birth were included. The focus of this review was on
research conducted with Black expectant fathers given the limited data on the
association between paternal psychosocial factors and PTB. This review only
highlights studies that examined the associations of maternal psychosocial
factors and PTB. It does not present a comprehensive review of studies on
maternal factors given the extent of the studies that examined these
associations. RESULTS: Pregnant Black women are more likely to report living in
disadvantaged neighborhoods; experiencing racial discrimination, psychological
stress, and depressive symptoms; using avoidance coping; and reporting lower
levels of social support compared with White women. Limited data suggest that
Black expectant fathers experience higher rates of everyday unfair treatment
because of race/ethnicity compared with White fathers. Research suggests that
these psychosocial factors have been related to PTB among pregnant Black women;
however, research is limited on examining these associations among expectant
Black fathers. CLINICAL IMPLICATIONS: Maternal-child nurses are in the position
to assess these psychosocial factors among expectant parents. Nurses should also
assess risk factors for PTB for both expectant parents and provide support to
couples who are at risk for PTB.
PMID- 29944479
TI - Hearing in Real-Life Environments (HERE): Structure and Reliability of a
Questionnaire on Perceived Hearing for Older Adults.
AB - OBJECTIVES: The ability to hear in a variety of social situations and
environments is vital for social participation and a high quality of life. One
way to assess hearing ability is by means of self-report questionnaire. For
questionnaires to be useful, their measurement properties, based on careful
validation, have to be known. Only recently has consensus been reached concerning
how to perform such validation and been published as COSMIN (consensus-based
standards for the selection of health status measurement instruments) guidelines.
Here the authors use these guidelines to evaluate the measurement properties of
the "Hearing in Real-Life Environments" (HERE) questionnaire, a newly developed
self-report measure that assesses speech perception, spatial orientation, and the
social-emotional consequences of hearing impairment in older adults. The aim is
to illustrate the process of validation and encourage similar examinations of
other frequently used questionnaires. DESIGN: The HERE questionnaire includes 15
items with a numeric rating scale from 0 to 10 for each item and allows the
assessment of hearing with and without hearing aids. The evaluation was performed
in two cohorts of community-dwelling older adults from Finland (n = 581, mean 82
years) and the United Kingdom (n = 50, mean 69 years). The internal structure of
the questionnaire and its relationship to age, hearing level, and self-reported
and behavioral measures of speech perception was assessed and, when possible,
compared between cohorts. RESULTS: The results of the factor analysis showed that
the HERE's internal structure was similar across cohorts. In both cohorts, the
factor analysis showed a satisfactory solution for three factors (speech hearing,
spatial hearing, and socio-emotional consequences), with a high internal
consistency for each factor (Cronbach's alpha's for the factors from 0.90 to
0.97). Test-retest analysis showed the HERE overall mean score to be stable and
highly replicable over time (intraclass correlation coefficient = 0.86, standard
error of measurement of the test score = 0.92). The HERE overall mean score
correlated highly with another self-report measure of speech perception, the
Speech Spatial Qualities of Hearing questionnaire (standardized regression
coefficient [beta] = -0.75, p < 0.001), moderately highly with behaviorally
assessed hearing level (best-ear average: beta = 0.45 to 0.46), and moderately
highly with behaviorally measured intelligibility of sentences in noise (beta =
0.50, p < 0.001). CONCLUSIONS: Using the COSMIN guidelines, the authors show that
the HERE is a valid, reliable, and stable questionnaire for the assessment of
self-reported speech perception, sound localization, and the socio-emotional
consequences of hearing impairment in the context of social functioning. The
authors also show that cross-cultural data collected using different data
collection strategies can be combined with a range of statistical methods to
validate a questionnaire.This is an open-access article distributed under the
terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC),
where it is permissible to download, share, remix, transform, and buildup the
work provided it is properly cited. The work cannot be used commercially without
permission from the journal.
PMID- 29944480
TI - Identification of Gambling Problems in Primary Care: Properties of the NODS-CLiP
Screening Tool.
AB - INTRODUCTION: There are several brief screening tools for gambling that possess
promising psychometric properties, but have uncertain utility in generalist
healthcare environments which prioritize prevention and brief interventions. This
study describes an examination of the National Opinion Research Centre Diagnostic
and Statistical Manual of Mental Disorders Screen for Gambling Problems (NODS
CLiP), in comparison with the Problem Gambling Severity Index (PGSI), when used
to operationalize gambling problems across a spectrum of severity. METHODS: Data
were obtained from 1058 primary care attendees recruited from 11 practices in
England who completed various measures including the NODS-CLiP and PGSI. The
performance of the former was defined by estimates of sensitivity, specificity,
positive predictive values (PPVs), and negative predictive values (NPVs), when
PGSI indicators of problem gambling (5+) and any gambling problems (1+),
respectively, were reference standards. RESULTS: The NODS-CLiP demonstrated
perfect sensitivity for problem gambling, along with high specificity and a NPV,
but a low PPV. There was much lower sensitivity when the indicator of any
gambling problems was the reference standard, with capture rates indicating only
20% of patients exhibiting low to moderate severity gambling problems (PGSI 1-4)
were identified by the NODS-CLiP. CONCLUSIONS: The NODS-CLiP performs well when
identifying severe cases of problem gambling, but lacks sensitivity for less
severe problems and may be unsuitable for settings which prioritize prevention
and brief interventions. There is a need for screening measures which are
sensitive across the full spectrum of risk and severity, and can support
initiatives for improving identification and responses to gambling problems in
healthcare settings such as primary care.
PMID- 29944481
TI - Treatment of Kratom Dependence With Buprenorphine-Naloxone Maintenance.
AB - INTRODUCTION: Use of the unregulated herbal supplement kratom is on the rise in
the United States. We present a case series of 2 patients who developed kratom
dependence and withdrawal who were successfully transitioned to buprenorphine
naloxone maintenance. CASE SUMMARY: Two patients using kratom to self-treat
chronic pain after prescription opioids were discontinued presenting to our
clinic with evidence of kratom dependence and withdrawal. On examination, both
patients showed signs of mild opioid withdrawal. Both patients were successfully
transitioned to buprenorphine-naloxone maintenance via home initiation with
control of both their opioid withdrawal and chronic pain. CONCLUSIONS: Kratom use
is on the rise and with increasing evidence of developing opioid-type dependence
due to chronic kratom use. This case series shows that buprenorphine can be used
to treat kratom dependence and underlying chronic pain that drives it use.
PMID- 29944482
TI - Critical Friends: Health Professionals' Experiences of Collegial Feedback in a
Clinical Setting.
AB - INTRODUCTION: A critical friend is a trusted person who asks provocative
questions, provides data to be examined through another lens, and offers critique
of a person's work as part of collegial feedback. However, empirical evidence
presenting the use of collegial feedback to develop health professionals'
competence in clinical settings seems to be scarce. The aim of this study was to
explore health professionals' experiences of observing each other as critical
friends in a clinical setting, as part of a continuous professional development
initiative. METHODS: The study was designed as a qualitative inductive study.
Reflective journals written by health professionals (n = 57) were analyzed using
thematic networks. The health professionals represented registered nurses and
registered nurses with different specialist education (eg, in pediatrics, mental
health, intensive care, and anesthesiology), biomedical scientists, occupational
therapists, physiotherapists, and dental hygienists. RESULTS: Health
professionals can successfully use collegial feedback and benefit from critical
friendships in clinical settings as it offers ample opportunities for reflection
before, during, and after the observation. A key finding was that to incorporate
changes to professional practice, each individual needs to not only act as a
critical friend but also experience being observed by a critical friend.
DISCUSSION: Based on the results of this study, it seems worthwhile to implement
and further develop opportunities for health professionals to act as critical
friends. We suggest that future research explore not only how professional
competence develops over time but also how it impacts on health-related outcomes
for patients.
PMID- 29944483
TI - Multireader Study on the Diagnostic Accuracy of Ultrafast Breast Magnetic
Resonance Imaging for Breast Cancer Screening.
AB - OBJECTIVES: Breast cancer screening using magnetic resonance imaging (MRI) has
limited accessibility due to high costs of breast MRI. Ultrafast dynamic contrast
enhanced breast MRI can be acquired within 2 minutes. We aimed to assess whether
screening performance of breast radiologist using an ultrafast breast MRI-only
screening protocol is as good as performance using a full multiparametric
diagnostic MRI protocol (FDP). MATERIALS AND METHODS: The institutional review
board approved this study, and waived the need for informed consent. Between
January 2012 and June 2014, 1791 consecutive breast cancer screening examinations
from 954 women with a lifetime risk of more than 20% were prospectively
collected. All women were scanned using a 3 T protocol interleaving ultrafast
breast MRI acquisitions in a full multiparametric diagnostic MRI protocol
consisting of standard dynamic contrast-enhanced sequences, diffusion-weighted
imaging, and T2-weighted imaging. Subsequently, a case set was created including
all biopsied screen-detected lesions in this period (31 malignant and 54 benign)
and 116 randomly selected normal cases with more than 2 years of follow-up. Prior
examinations were included when available. Seven dedicated breast radiologists
read all 201 examinations and 153 available priors once using the FDP and once
using ultrafast breast MRI only in 2 counterbalanced and crossed-over reading
sessions. RESULTS: For reading the FDP versus ultrafast breast MRI alone,
sensitivity was 0.86 (95% confidence interval [CI], 0.81-0.90) versus 0.84 (95%
CI, 0.78-0.88) (P = 0.50), specificity was 0.76 (95% CI, 0.74-0.79) versus 0.82
(95% CI, 0.79-0.84) (P = 0.002), positive predictive value was 0.40 (95% CI, 0.36
0.45) versus 0.45 (95% CI, 0.41-0.50) (P = 0.14), and area under the receiver
operating characteristics curve was 0.89 (95% CI, 0.82-0.96) versus 0.89 (95% CI,
0.82-0.96) (P = 0.83). Ultrafast breast MRI reading was 22.8% faster than reading
FDP (P < 0.001). Interreader agreement is significantly better for ultrafast
breast MRI (kappa = 0.730; 95% CI, 0.699-0.761) than for the FDP (kappa = 0.665;
95% CI, 0.633-0.696). CONCLUSIONS: Breast MRI screening using only an ultrafast
breast MRI protocol is noninferior to screening with an FDP and may result in
significantly higher screening specificity and shorter reading time.
PMID- 29944484
TI - Influence of Cross-Section Design and Vertical Misfit on Stress Distribution in
Overdenture Retaining System: 3-Dimensional Finite Element Analysis.
AB - PURPOSE: To evaluate by 3-dimensional (3-D) finite element analysis the stress
generated on overdenture-retaining bar system with different cross sections
(round, ovoid, or Hader) and misfit levels (50, 100, and 200 MUm) manufactured
with different metallic alloys (Au type IV, Ag-Pd, Ti cp, and Co-Cr). MATERIALS
AND METHODS: Three-dimensional finite element models were modeled using specific
3-D software (SolidWorks) and imported into mechanical simulation software
(ANSYS). A displacement simulating the settlement of the screw was performed
until the infrastructure was settled properly on the prosthetic platform.
RESULTS: Higher misfit levels caused higher stress on the overdenture-retaining
bar system components, where (1) Hader bar presented the highest values (bar =
730.71; screw = 59.66, and periimplant bone tissue = 42.96, in megapascal) and
(2) round bars made with type IV Au alloy presented lower stress values on the
bar framework (193.99 MPa) and screw (10.27 MPa). CONCLUSIONS: Higher vertical
misfit increased the stress values on the overdenture-retaining bar system;
complex cross-sectional designs increased stress values on the bar framework,
prosthetic screw, and periimplant bone tissue; stiffer alloys caused higher
stress values on all the studied conditions.
PMID- 29944485
TI - Optimal Multimodal Analgesia Treatment Recommendations for Total Joint
Arthroplasty: A Critical Analysis Review.
PMID- 29944487
TI - Total Wrist Arthroplasty.
PMID- 29944486
TI - Scapular Winging in the Pediatric Patient.
PMID- 29944489
TI - Advancing theory on the multilevel role of leadership in the implementation of
evidence-based health care practices.
AB - BACKGROUND: Top managers' transformational leadership is associated with
significant influence on subordinates. Yet little is known about the extent to
which top managers' transformational leadership influences middle managers'
implementation leadership and, ultimately, frontline staff delivery of evidence
based health care practices. PURPOSE: To test a multilevel leadership model
examining the extent to which top managers' transformational leadership, as
mediated by implementation leadership of middle managers (i.e., those who
supervise direct clinical services), affects staff attitudes toward evidence
based practices (EBPs) and their implementation. METHODOLOGY/APPROACH: We used
data collected in 2013 from 427 employees in 112 addiction health services
programs in Los Angeles County, California. We relied on hierarchical linear
models with robust standard errors to analyze multilevel data, individuals nested
in programs. We conducted two path models to estimate multilevel relationships
with two EBPs: contingency management and medication-assisted treatment. RESULTS:
Findings partially supported our theory-driven multilevel leadership model.
Specifically, results demonstrated that middle managers' implementation
leadership mediated the relationship between top managers' transformational
leadership and attitudes toward EBPs. At the same time, they showed the mediated
relationship for delivery of contingency management treatment was only marginally
significant (standardized indirect effect = .006, bootstrap p = .091). We did not
find a mediation effect for medication-assisted treatment. DISCUSSION: Findings
advance leadership theory in health care, highlighting the importance of middle
managers' implementation leadership in transmitting the influence of top
managers' transformational leadership on staff attitudes toward EBPs. The full
path model shows the extent to which transformational leadership may influence
staff implementation of innovative practices as mediated through staff attitudes
toward EBPs and middle managers' implementation leadership. PRACTICE
IMPLICATIONS: Our findings have implications for developing a multilevel
leadership approach to implementation in health care. Leadership development
should build on different competencies based on managers' level but align
managers' priorities on the same implementation goals.This is an open-access
article distributed under the terms of the Creative Commons Attribution-Non
Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to
download and share the work provided it is properly cited. The work cannot be
changed in any way or used commercially without permission from the journal.
PMID- 29944488
TI - Serum sodium, model for end-stage liver disease, and a recent invasive procedure
are risk factors for severe acute-on-chronic liver failure and death in cirrhotic
patients hospitalized with bacterial infection.
AB - INTRODUCTION: Bacterial infection is present in up to 30% of hospitalized
cirrhotic patients. It can lead, even after its resolution, to organ dysfunction
and even acute-on-chronic liver failure (ACLF). It is the precipitating factor of
ACLF in one third of the cases and is the main cause of mortality in patients
with liver cirrhosis. OBJECTIVES: The aim of this study was to evaluate the
prevalence and identify early risk factors for severe ACLF and death in
hospitalized patients with liver cirrhosis with bacterial infection. PATIENTS AND
METHODS: This was a prospective observational study. Hospitalized patients with
liver cirrhosis and bacterial infection were included. Clinical and laboratory
data and their evolution to organ dysfunction and death were assessed. A
statistical analysis were carried out to identify predictors of severe ACLF and
in-hospital mortality. RESULTS: This study included 88 patients. ACLF was
observed in 62 (70%) patients, with 48 (55%) grade 2 or higher. Of the 27 deaths
(31% of all patients), 26 had severe ACLF (54% mortality) (P<0.0001). The
independent risk factors for ACLF of at least 2 and death were baseline serum
sodium [odds ratio (OR): 0.874; P=0.01, and OR: 0.9, P=0.04], initial MELD (OR:
1.255, P=0.0001, and OR: 1.162, P=0.005), and a recent invasive procedure (OR:
3.169, P=0.01, and OR: 6.648, P=0.003). CONCLUSION: Lower serum sodium values,
higher MELD scores at diagnosis of infection, and a recent history of invasive
procedures were independent risk factors for severe ACLF and death in patients
with cirrhosis and bacterial infection.
PMID- 29944490
TI - A rare mutation in the EPG5 gene causes Vici syndrome.
PMID- 29944491
TI - Effects of Childhood Life Events on Adjustment Problems in Adolescence: A
Longitudinal Study.
AB - OBJECTIVES: Stressful life events (SLEs) have been associated with adjustment
problems in adolescence (APA) in cross-sectional studies. Using a longitudinal
cohort, we examined the influence of these events and predefined covariates on
APA and compared internalizing and externalizing trajectories among children with
many versus few SLEs. METHODS: Data were obtained from the Study of Early Child
Care and Youth Development. One thousand three hundred sixty-four children and
their families were followed from child's birth until age 15 years. Adjustment
problems at age 15 years were defined as high (>60 T-score) internalizing and/or
externalizing problems on the Youth Self-Report and Child Behavior Checklist.
Stressful life events were evaluated at 54 months, and third and fifth grade.
Categories created by mixture model analyses for covariates were used in logistic
regressions to predict adjustment problems. RESULTS: Mothers reported higher
rates of adjustment problems than adolescents (21.1% vs 16.3%; p < 0.0001).
Adjustment problems were associated with more SLEs (odds ratio [OR] = 1.7; p =
0.0042), male sex (OR = 1.9; p = 0.001), child's high emotional reactivity (OR =
1.6; p = 0.01), and paternal depression (OR = 2.1; p = 0.0165). Analysis using
the mother's report of adjustment problems showed the same predictors, as well as
lower maternal education level (OR = 3.5; p = 0.0003), and child's friendship
quality (OR = 0.4; p = 0.005). Higher internalizing and externalizing T-scores
were apparent in children with more SLEs from 2 years of age onward (ps <
0.0001). CONCLUSION: After adjusting for multiple covariates, SLEs during
childhood predicted adjustment problems. Our results suggest that emotional
reactivity and paternal depression play a role in the development of APA.
PMID- 29944492
TI - Utilization of Facial Image Analysis Technology for Blink Detection: A Validation
Study.
AB - PURPOSE: The assessment of anterior eye diseases and the understanding of
psychological functions of blinking can benefit greatly from a validated blinking
detection technology. In this work, we proposed an algorithm based on facial
recognition built on current video processing technologies to automatically
filter and analyze blinking movements. We compared electrooculography (EOG), the
gold standard of blinking measurement, with manual video tape recording counting
(mVTRc) and our proposed automated video tape recording analysis (aVTRa) in both
static and dynamic conditions to validate our aVTRa method. METHODS: We measured
blinking in both static condition, where the subject was sitting still with chin
fixed on the table, and dynamic condition, where the subject's face was not fixed
and natural communication was taking place between the subject and interviewer.
We defined concordance of blinks between measurement methods as having less than
50 ms difference between eyes opening and closing. RESULTS: The subjects
consisted of seven healthy Japanese volunteers (3 male, four female) without
significant eye disease with average age of 31.4+/-7.2. The concordance of EOG
vs. aVTRa, EOG vs. mVTRc, and aVTRa vs. mVTRc (average+/-SD) were found to be
92.2+/-10.8%, 85.0+/-16.5%, and 99.6+/-1.0% in static conditions and 32.6+/
31.0%, 28.0+/-24.2%, and 98.5+/-2.7% in dynamic conditions, respectively.
CONCLUSIONS: In static conditions, we have found a high blink concordance rate
between the proposed aVTRa versus EOG, and confirmed the validity of aVTRa in
both static and dynamic conditions.
PMID- 29944493
TI - Postsurgical Cataract Prophylaxis With Intravitreal "Triamcinolone-Moxifloxacin"
May Not Be Optimal For Preventing Endophthalmitis.
AB - PURPOSE: Intravitreal injections of antibiotics and anti-inflammatories are used
by some cataract surgeons for surgical prophylaxis. To support this prophylaxis,
intravitreal triamcinolone-moxifloxacin (TM) and triamcinolone-moxifloxacin
vancomycin (TMV) were tested for preventing Staphylococcus aureus (SA)
endophthalmitis in rabbits. METHODS: Trademark formulations of TM (15/1 mg/mL)
and TMV (15/1/10 mg/mL) were intravitreally injected into seven groups of eight
rabbits each (A-G). Before intravitreal injection, the vitreous was first
challenged with clinical SA endophthalmitis isolates (5,000 colony-forming unit)
with varying minimum inhibitory concentrations (MICs in MUg/mL) to moxifloxacin
(denoted by the MIC at the end of each group listed): A) TMV-10, B) TM-10, C)
Saline-10, D) TM-2, E) Saline-2, F) TM-0.032, and G) Saline-0.032. After 24 hr,
the rabbit eyes were graded for clinical endophthalmitis and cultured for viable
SA. RESULTS: Rabbits treated with TMV and challenged by SA with a moxifloxacin
MIC of 10 MUg/mL did not present with endophthalmitis (0/8, no eyes with
endophthalmitis). For SA with moxifloxacin MICs of 10.0 and 2.0 MUg/mL, TM did
not prevent endophthalmitis (16/16, 100% of eyes with endophthalmitis). For SA
with a moxifloxacin MIC of 0.032 MUg/mL, endophthalmitis was prevented with TM
(0/8, no eyes with endophthalmitis). All saline-treated eyes developed
endophthalmitis (23/23, 100% of eyes with endophthalmitis). CONCLUSIONS:
Intravitreal monotherapy with TM did not provide consistent prevention of SA
endophthalmitis, whereas intravitreal TMV successfully prevented endophthalmitis
because of SA with elevated MIC values to moxifloxacin. Cataract surgeons need to
be aware that vancomycin seems to be essential for intravitreal prophylaxis to
cover moxifloxacin resistance.
PMID- 29944494
TI - Analysis of SmartPlug Insertion-Related Complications.
AB - PURPOSE: To evaluate the complications and the treatment results of SmartPlug
related complications. METHODS: Retrospective review of all patients from a
single medical hospital who received SmartPlug (Medennium, Inc., Irvine, CA)
insertions from October 2007 to February 2014. All patients who developed
SmartPlug-related canaliculitis and pyogenic granuloma were analyzed. Lacrimal
irrigation with antibiotics was performed in most patients. RESULTS: Six hundred
thirty-one eyes received SmartPlug insertion and 18 eyes developed SmartPlug
related complications (14 canaliculitis and 4 pyogenic granuloma). The mean time
interval from insertion to development of the complications is 3.0 (0.5-6.9)
years. Sixteen eyes received lacrimal irrigation with antibiotics, and all the
eyes showed improvement without recurrence. The other two eyes had recurrence of
granuloma pyogenica only after surgical excision. CONCLUSIONS: SmartPlug-related
complications, including canaliculitis and granuloma pyogenica, required long
term follow-up. Most of the complications can be cured by lacrimal irrigation of
antibiotics.
PMID- 29944495
TI - Predictability of the Achieved Lenticule Thickness in Small Incision Lenticule
Extraction for Myopia Correction.
AB - PURPOSE: To investigate the predictability of the achieved lenticule thickness in
small incision lenticule extraction (SMILE) for the correction of myopia.
METHODS: In this prospective study, a total of 80 eyes of 45 patients who
underwent the SMILE procedure were included. A Scheimpflug camera was used to
measure the preoperative and postoperative corneal topography. Achieved lenticule
thicknesses at the pupil center and corneal vertex were calculated by subtracting
the postoperative corneal thickness at the pupil center and corneal vertex from
preoperative corresponding values. Predictability between the achieved and
VisuMax readout at different locations (the pupil center and corneal vertex) and
postoperative visits (postoperative day 1 and 6 months) were evaluated using a
general linear model. RESULTS: Achieved lenticule thickness at the pupil center
and corneal vertex showed good correlation at both postoperative day 1 (pupil
center: r=0.914, corneal vertex: r=0.903) and 6 months (pupil center: r=0.886,
corneal vertex: r=0.866). The achieved lenticule thickness at postoperative day 1
was 8.5-MUm thinner at the pupil center and 9.6-MUm thinner at the corneal vertex
than the VisuMax readout. CONCLUSIONS: This study suggests that the
predictability between the achieved and VisuMax readout is favorable. The
lenticule thickness at the pupil center is closer to the VisuMax readout than
corneal vertex.
PMID- 29944496
TI - Is Sesamol Effective in Corneal Neovascularization?
AB - OBJECTIVES: To evaluate the effects of topically and subconjunctivally
administered sesamol on experimentally induced corneal neovascularization in
rats. METHODS: Fifty-six right eyes of 56 Wistar Albino rats were chemically
cauterized to induce corneal neovascularization in this experimental and
comparative study. The subjects were divided into eight groups: topical sesamol
(group 1), subconjunctival sesamol (group 2), topical bevacizumab (group 3),
subconjunctival bevacizumab (group 4), topical bevacizumab+ sesamol (group 5),
subconjunctival bevacizumab+ sesamol (group 6), topical Tween 80 (group 7), and
control (group 8). The amount of subconjunctivally injected sesamol and
bevacizumab was 1.25 mg each. Topical groups were administered 10 mg/mL drops
twice daily. The control group was left untreated. To evaluate the degree of
corneal neovascularization, digital photographs and corneal sections stained with
hematoxylin-eosin and CD31 were used. RESULTS: When photographs of
neovascularization areas were examined, all treatment groups showed statistically
significant differences when compared with the control group (P<0.001). Topical
sesamol was found to be more effective when compared with subconjunctival sesamol
(P=0.003). Topical sesamol+ bevacizumab was found to be more effective when
compared with topical bevacizumab (P=0.018). The numbers of new corneal vessels
were as follows: 12.28+/-6.29 in group 1, 36.85+/-12.8 in group 2, 18.85+/-7.71
in group 3, 16.85+/-8.70 in group 4, 19.57+/-8.56 in group 5, 22.57+/-7.43 in
group 6, 45.00+/-11.29 in group 7, and 51.16+/-5.91 in group 8 (P<0.001).
CONCLUSIONS: The outcomes of this study suggest antiangiogenic effects of
sesamol. The use of topical sesamol monotherapy or sesamol combined with
bevacizumab may be options for the prevention of corneal neovascularization.
PMID- 29944497
TI - Long-Term Clinical Observation of Posterior Chamber Phakic Intraocular Lens
Implantation in Young Population.
AB - OBJECTIVES: To compare the clinical outcomes and vision-related quality of life
after implantable collamer lens (ICL) implantation for younger patients (17 years
<= age <=21 years) and for older patients (age >21 years). METHODS: Design:
Retrospective observational study. This study-enrolled patients underwent ICL
implantation and finished 5-year follow-up who were divided into two groups based
on age. Uncorrected distance visual acuity and corrected distance visual acuity
(CDVA), refractions for the evaluation of efficacy, safety, stability, and
predictability, intraocular pressure, corneal endothelial cell, ICL vaults,
higher-order aberration (HOA), contrast sensitivity (CS) functions, adverse
events, and quality of life were evaluated on 1, 3, 7, 14 days, 1, 3, 6 months
and 1, 3, 5 years after surgery. RESULTS: The study enrolled 164 eyes (82
patients), 84 in younger group (17 years <= age <=21 years) and 80 in older group
(age >21 years). The mean postoperative log of minimal angle of resolution CDVA
of younger group was better than those of older group. The mean spherical
equivalent values were more myopic in younger group than older group. As for CS
and HOA, the younger and older groups showed similar data. The NEI-RQL scores of
dependence on correction, worry, suboptimal correction, appearance, and
satisfaction of older group were higher, whereas the score of symptom and near
vision was worse. Both groups showed similar results in vaults, endothelial cell
density and adverse events. CONCLUSIONS: The ICL performed well for the ametropia
correction of both younger and older patients throughout the 5-year period. In
the younger group, the visual quality was even better, but the myopic shift was
quicker.
PMID- 29944498
TI - Response of the Aging Eye to First Day of Modern Material Contact Lens Wear.
AB - OBJECTIVES: To investigate the ocular surface of an aged population wearing a
daily disposable contact lens (CL) over their 1st day of wear. METHODS: Forty
eyes from 40 presbyopic subjects were fitted a daily CL (Delefilcon A). Tear
osmolarity, tear meniscus area (TMA), and ocular surface aberrations (total
higher-order root mean square [RMS]) were assessed at baseline (t0), at 20 min
(t1) and after 8 hr (t2) of wear. Fluorescein corneal and conjunctival staining
and tear breakup time (TBUT) were performed at t0 and t2. RESULTS: No
statistically significant changes were found between t0, t1, and t2 for TMA and
between t0 and t2 for fluorescein corneal and conjunctival staining. Tear breakup
time worsened by the end of the day from 10.4+/-0.4 sec t0 to 9.0+/-0.3 sec t2
(P<0.05). Osmolarity showed significant changes between t0 306.9+/-2.3 mOsm/L and
t1 312.4+/-2.4 mOsmol/L (P=0.02) but returned to baseline values at 8 hr
(310.40+/-2.26 mOsm/L; P=0.09). Total higher-order RMS showed significant changes
between t0 0.38+/-0.02 MUm and t1 0.61+/-0.04 MUm (P<=0.001) and between t0 and
t2 0.64+/-0.41 MUm (P<=0.001). CONCLUSIONS: Delefilcon A may induce measures
changes (osmolarity and TBUT values) in a presbyopic population; however, TMA and
vital staining were maintained at the baseline level over the day.
PMID- 29944499
TI - Comparison of Different Corneal Power Readings From Pentacam in Post-laser In
Situ Keratomileusis Eyes.
AB - OBJECTIVES: To compare the various Pentacam-measured K-readings with the clinical
history method (CHM) in eyes that have undergone myopic laser in situ
keratomileusis (LASIK). METHODS: In this prospective study, Pentacam examination
was performed in 71 eyes 1 month after myopic LASIK. The true net power (TNP) 4
mm, total corneal refractive power (TCRP) 4 mm, equivalent K-reading (EKR) 4.0
mm, and EKR 4.5 mm obtained from the same scan were compared with the K derived
from CHM. RESULTS: The average baseline spherical equivalence was -5.44+/-2.38 D.
After LASIK, the mean KCHM was 37.67+/-2.13 D, TCRP4mm was 37.14+/-1.79 D, TNP4mm
was 36.88+/-1.76 D, EKR4.0mm was 37.58+/-1.94 D, and EKR4.5mm was 37.51+/-1.94 D.
TCRP4mm, TNP4mm, and EKR4.5mm showed a statistically significant deviation from
the KCHM, with the mean error being 0.53 D, 0.79 D, and 0.16 D, respectively
(P<0.05). Only the EKR4.0mm showed no statistically significant difference from
the KCHM (mean error 0.09 D, P=0.23). The EKR4.0mm also had the narrowest 95%
limits of agreement (LoA) (-1.10 to +1.28 D), whereas both TCRP4mm and TNP4mm had
a wider LoA (-0.88 to +1.95 D and -0.62 to +2.20 D, respectively). All four
Pentacam K-readings had a strong and statistically significant correlation with
the KCHM. CONCLUSIONS: Using the CHM as reference, the EKR4.0mm demonstrated the
closest agreement when compared with the EKR4.5mm, TNP4mm, and TCRP4mm obtained
from the same scan.
PMID- 29944500
TI - "Therapeutic Penetrating Keratoplasty: A Retrospective Review".
AB - PURPOSE: To report the indications, outcomes, and complications of therapeutic
penetrating keratoplasty (Th PK) in patients with corneal perforation and/or
nonhealing corneal ulceration. METHODS: A retrospective review was conducted of
51 eyes of 51 patients undergoing Th PK between January 1, 2006 and April 15,
2016. Data collected included patient demographics, visual acuity (VA), size of
the corneal infiltrate and epithelial defect, degree of corneal
thinning/perforation, microbiological results, surgical details, and
postoperative complications. RESULTS: The average age at presentation was 56.0
years (range 6-92 years), and most of the patients were females (n=31, 60.8%). Th
PK was performed for corneal perforation in 28 eyes (54.9% of cases), nonhealing
corneal ulcer in 16 eyes (31.4% of cases), and imminent risk of corneal
perforation in 7 eyes (13.7% of cases). Infection was the most common reason for
performing a Th PK and was present in 92.3% (47/51) of all cases. Of the
infectious cases, the most common etiologies were bacterial (44.7%, 21/47) and
fungal (31.9%, 15/47). The most common identifiable risk factor for undergoing a
Th PK was a history of contact lens wear, which was seen in 32.7% of patients.
Initial anatomic success was achieved in all patients after performing Th PK.
Most patients (33/51; 64.7%) had clear grafts at their last follow-up
examination. There was an improvement in VA in 70.2% (33/47, where data were
available) of the patients at the final postoperative visit compared with the
preoperative visit. Average best postoperative VA (1.14+/-0.88 logarithm of the
minimum angle of resolution [LogMAR]; 20/276) was significantly better than the
presenting (1.98+/-0.68 LogMAR; 20/1910) and preoperative (2.18+/-0.55 LogMAR;
20/3,027) visual acuities (P<0.0001). The most common complication after Th PK
was cataract, which was present in 81.8% (27/33) of phakic eyes in which lens
status could be assessed, followed by graft failure (47.1%; 24/51), and secondary
glaucoma (45.1%; 23/51). Five eyes developed infection in the therapeutic graft,
four eyes had persistent corneal epithelial defect at their last follow-up visit,
and two eyes underwent evisceration. CONCLUSIONS: Therapeutic penetrating
keratoplasty achieves anatomic success and it is a useful procedure for restoring
a stable cornea in cases in which infection fails to heal or when the cornea
perforates. Furthermore, Th PK achieves corneal clarity and improves vision in
most patients.
PMID- 29944501
TI - Vision Improvement and Compliance With the Use of Orthokeratology Lenses in
School Children: A Sample From Five Primary Schools in Northern Taiwan.
AB - PURPOSE: To assess the visual acuity and compliance with the use of
orthokeratology lenses (OrthoK) in school children. METHODS: A retrospective
study was conducted to determine the education-related factors influencing the
improvement in visual acuity in myopic students using OrthoK in five primary
schools in Taiwan. RESULTS: Of the 5,173 eligible students from five primary
schools, 1906 (36.8%) students were diagnosed with myopia. Among 201 (10.6%)
students wearing OrthoK, 69.7% had used them for at least 1 year, 53.2% achieved
visual acuity greater than 0.8 (6/7.5, log of minimal angle of resolution 0.1) in
school, and 49.8% had received health education related to OrthoK care. Multiple
logistic regression analysis showed that a higher possibility to achieve visual
acuity greater than 0.8 was associated with more than 1-year use of OrthoK, good
compliance, and receiving health education from an ophthalmologist. CONCLUSION:
It is important that children wearing OrthoK receive education and comply with
the use of OrthoK for visual acuity improvement.
PMID- 29944502
TI - Scleral Lens Issues and Complications Related to a Non-optimal Fitting
Relationship Between the Lens and Ocular Surface.
AB - INTRODUCTION: The advent of high oxygen permeability (Dk) of rigid contact lens
materials has reduced complications related to hypoxia when using scleral contact
lenses (ScCLs). However, new issues and complications have emerged. Some of these
issues and complications are caused by the nonoptimal fitting relationship with
the underlying ocular surface, which may pose a challenge in their management.
METHOD: PubMed searches using different keywords and an investigation into the
issues and complications etiology were conducted. Detailed guidelines for their
management are provided. RESULTS: The literature provides a few reports of severe
adverse reactions to ScCLs. The most common issues, unique to ScCL wear, have
been described. Likewise, other anomalies in ScCL fitting may affect patient
satisfaction and lead to drop out, promoting eye surgery or dramatic
psychological effects. The management of these issues and complications may be
also frustrating for clinicians who will, in turn, rarely, or not at all,
prescribe them. CONCLUSION: Scleral contact lenses intimidate practitioners
because of their large diameter and the lack of knowledge in regard to the
fitting process but especially because of the challenging management of issues
and complications that may occur relating to the lens fitting relationship with
the underlying ocular surface. A detailed description of the etiology and
management of these anomalies will allow practitioners to gain more confidence in
fitting ScCLs and prescribe them more often. Patients are the primary
beneficiaries from wearing these large rigid lenses; ScCLs represent a life
changing event for many patients.
PMID- 29944503
TI - Effects of Preoperative Topometric Indices on Visual Gain After Intracorneal Ring
Segment Implantation For Keratoconus.
AB - OBJECTIVES: To assess the corneal topometric parameters that can be predictive
for better visual gain after intracorneal ring segment (ICRS) implantation in
eyes with keratoconus. METHODS: A total of 42 eyes of 32 patients who underwent
ICRS implantation at Dokuz Eylul University, Deparment of Ophthalmology, Cornea
Divison were included. Changes in uncorrected distance visual acuity (UDVA),
corrected distance visual acuity (CDVA), refractive errors, and corneal
topometric indices measured using Scheimpflug topography (Pentacam, Oculus) were
evaluated retrospectively. RESULTS: After creation of intrastromal tunnels of
5.01+/-0.03 mm inner diameter, 5.71+/-0.03 mm outer diameter and at 384.21+/
34.12 MUm depth, 1 or 2 ICRS of 150 to 350 um thickness and 90 to 210 degrees
arc length were implanted. Preoperative UDVA of 0.09+/-0.10 and CDVA of 0.29+/
0.14 Snellen lines improved postoperatively to 0.42+/-0.26 and 0.62+/-0.24,
respectively (P<0.001 for both). Preoperative spherical equivalent of -6.35+/
4.58D and refractive astigmatism of -5.89+/-2.40D decreased to -3.59+/-3.86 and
2.25+/-1.66D, retrospectively (P<0.001 for both). Strong negative correlations
were detected between preoperative mean simulated keratometry (SimKavg)/index of
surface variance (ISV) and changes in UDVA/CDVA (P<0.01, for all). Postoperative
change in ISV was positively correlated with thicknesses of implanted rings.
Change in topographical keratoconus classification was positively and change in
index of vertical asymmetry was negatively correlated with number of implanted
rings (P<0.05 for all). CONCLUSIONS: Preoperative ISV value seems to be
beneficial in predicting visual gain after ICRS implantation, in addition to
SimKavg. Future work on new nomograms for ICRS selection that include ISV,
besides refractive, topographic, and cone location data, is warranted.
PMID- 29944504
TI - Investigation of the Effect of Orthokeratology Lenses on Quality of Life and
Behaviors of Children.
AB - PURPOSE: To investigate the changes in the quality of life and behaviors in
children before and after wearing orthokeratology lenses and to analyze the
potential impact of orthokeratology lenses on children's quality of life,
behaviors, and the progression of myopia. METHODS: A total of 100 children
receiving orthokeratology lenses in the People's Hospital of Hebei Province and
the Nanjing First Hospital from January 2016 to February 2017 were enrolled in
this study. A questionnaire survey was conducted for the orthokeratology lenses
wearers before and 3 months after wearing the orthokeratology lenses, and
analysis was performed for the 69 valid questionnaires. RESULTS: The scores of
symptom module, entertainment module, and study and life module marked by the
children differed significantly 3 months after wearing the orthokeratology
lenses. Among 20 entries, the life quality scores of nine surveys before and
after wearing lenses were statistically significant (P<0.05). The main reason why
the children chose orthokeratology lenses was more convenience in athletic
activities (43.5%). The majority of children (75.4%) were willing to accept
orthokeratology lenses to correct vision and to alleviate myopia progression.
CONCLUSION: Orthokeratology lenses have a good effect on children's quality of
life, behaviors, and psychology. The children who wore lenses were more self
confident, more willing to try new things, and more active in participating in
sports and entertainment, resulting in an increasing trend of the total time
spent on outdoor activities.
PMID- 29944505
TI - Evaluation of Long-Term Silicone Hydrogel Use on Ocular Surface Inflammation and
Tear Function in Patients With and Without Meibomian Gland Dysfunction.
AB - OBJECTIVES: To determine whether silicone hydrogel (SH) contact lens (CL) use,
with or without meibomian gland dysfunction (MGD), promotes ocular surface
inflammation. METHODS: Subjects wearing SH-CL for at least 6 months who also had
coexisting MGD (group 1, n=20), SH-CL users who did not have MGD (group 2, n=20),
patients who had MGD but did not use CL (group 3, n=20), and healthy CL-naive
individuals with no known systemic or ocular diseases (group 4, n=20) were
included in this cross-sectional, single-center study. All subjects underwent
tear function tests consisting of tear break-up time (tBUT), ocular surface
staining, Schirmer test, and the Ocular Surface Disease Index (OSDI)
questionnaire, as well as determination of tear IL-1RA, IL-1beta, IL-2, IL-2R, IL
4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IFN-alpha, IFN
gamma, TNF-alpha, granulocyte-macrophage colony-stimulating factor, IP-10,
monokine induced by gamma interferon, RANTES, eotaxin, MIP-1alpha, MIP-1beta, and
MCP-1 levels using Luminex multicytokine immunobead assay. Intergroup comparisons
were made using one-way analysis of variance or Kruskal-Wallis test. RESULTS: The
tBUT was lower (P=0.048) and ocular surface staining (P=0.032) as well as OSDI
scores (P=0.001) were higher in group 1 but not in groups 2 or 3 when compared
with those in the control group. Tear cytokine levels were similar across all
groups. None of the tear cytokine levels were elevated in CL wearers (groups 1
and 2) or those with MGD (groups 1 and 3) as compared to those in control
subjects. CONCLUSION: Silicone hydrogel contact lens use with concomitant MGD is
not associated with cytokine-driven ocular surface inflammation but may impact
tear function leading to dry eye symptoms.
PMID- 29944506
TI - Circular Keratotomy Combined With Wedge Resection in the Management of High
Astigmatism After Penetrating Keratoplasty.
AB - OBJECTIVE: To evaluate the effectiveness of circular keratotomy combined with
wedge resection for the management of high astigmatism after penetrating
keratoplasty (PK). METHODS: The study included seven eyes of seven patients with
previous PK who underwent circular keratotomy combined with wedge resection. The
uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA),
spherical equivalent (SE) refraction, and keratometric powers obtained by corneal
topography were evaluated. The power vector method was used to analyze the
astigmatic change postoperatively. RESULTS: The mean follow-up period was 18.42+/
8.56 months (range 12-33 months). Uncorrected visual acuity, BCVA, and SE were
improved in all eyes postoperatively. The mean preoperative astigmatism reduced
from 15.11+/-5.48 D (range, 10.0-24.4 D) to 4.98+/-3.01 D (range, 2.2-9.6 D),
postoperatively. According to the vector analysis, the overall mean surgically
induced astigmatism at last visit was 12.87+/-6.20 D. The most common
complication was the loosening of sutures occurred in five eyes within 2 months.
CONCLUSIONS: Circular keratotomy combined with corneal wedge resection is a
favorable option for the management of high astigmatism after PK.
PMID- 29944507
TI - Polymicrobial Keratitis With Cryptococcus curvatus, Candida parapsilosis, and
Stenotrophomonas maltophilia After Penetrating Keratoplasty: A Rare Case Report
With Literature Review.
AB - OBJECTIVES: To report the first case of fungal keratitis caused by Cryptococcus
curvatus after penetrating keratoplasty (PK) in an immunocompetent patient and to
describe its therapeutic challenge and long-term outcome. METHODS: An
interventional case report. RESULTS: A 54-year-old female patient underwent right
PK for lattice dystrophy. At 5-year post-PK, she developed a polymicrobial
keratitis caused by Candida parapsilosis, and Stenotrophomonas maltophilia at the
peripheral graft, which was successfully treated with topical antibiotic and
antifungal drops. One year later, another fungal keratitis occurred which
apparently resolved with antifungal treatment but recurred in an unusual fashion
and required a repeat PK revealing the diagnosis of C. curvatus keratitis. This
was confirmed by microbiological culture on Sabouraud dextrose agar, nuclear
ribosomal repeat regional sequencing of the D1-D2 and internal transcribed spacer
regions, and histopathological examination. Various topical, intracorneal, and
systemic antifungal treatments had been attempted but failed to resolve the
infection completely, necessitating a subsequent third PK. A further recurrence
was noted 16-month post-third PK, which was eradicated with multiple topical and
intracorneal antifungal treatment, and direct cryotherapy to the corneal abscess.
No further recurrence of C. curvatus was noted at 4-year follow-up. CONCLUSIONS:
Cryptococcus curvatus should be added to the known list of organisms capable of
causing fungal keratitis. Our experience suggests that this type of organism
could cause low-grade, grumbling infection, which may however be exceptionally
difficult to treat. Long-term eradication of this rare fungal keratitis could be
potentially achieved by intensive ocular and systemic antifungal treatment,
repeat therapeutic keratoplasties, and focal cryotherapy.
PMID- 29944508
TI - Relationship of Water Content With Silicon and Fluorine Contents of Silicone
Hydrogel Contact Lens Materials.
AB - OBJECTIVES: The relationship between water (W) content and silicon (Si) content
of silicone-hydrogel (SiHy) contact lens materials was inspected using identical
methodologies, equipment, and operators for materials composing 16 types of
commercially available SiHy contact lenses. Fluorine (F) content was included in
the analysis for the three materials also containing a fluoropolymer. One type of
lens consisted of a bulk SiHy material coated with thin layers of conventional
hydrogel. METHODS: SiHy materials were obtained in the form of 16 contact lens
brands purchased on the open market in a common range of refractive powers from
3 to +6 D in single lots. All test lenses were equilibrated at room temperature
in a standard saline recommended in the American National Standards Institute
Z80.20-2016 and International Organization for Standardization (ISO) 18369-4:2017
standards. W content was obtained gravimetrically, in %, according to those
standards for 16 lenses of each SiHy material. Si content was determined in %
using inductively coupled plasma optical emission spectroscopy for four digested
lenses of each material. F content was determined in % using an ion-selective
electrode for four combusted lenses of each of the three fluorinated SiHy
materials. W and Si contents of the bulk SiHy material of the coated lens were
estimated by computational exclusion of the hydrogel layers. RESULTS: The linear
coefficients of determination (R, n=16) were -0.7576 (relating mean dry Si
content [n=4] to mean W content [n=16]) and -0.8819 (relating mean hydrated Si
content [n=4] to mean W content [n=16]). When the 4 SiHy materials that were
fluorinated or coated were excluded from the analysis, the R values (n=12) were
0.8869 and -0.9263, respectively. When F contents and the coating were added to
the assessments, the linear coefficients of determination (R, n=16) became
0.8948 (relating mean dry [Si+F] content to mean W content) and -0.9397 (relating
mean hydrated [Si+F] content to mean W content). CONCLUSIONS: There is a
fundamental negative linear relationship between Si and W contents for SiHy
contact lens materials above 35% W content that is followed when F content and
hydrogel coatings are empirically added to the analysis below 35% W content. The
relationship was tightest for hydrated (Si+F) content and W content, for which
the regression equation had an R of -0.9397: (Si+F)=-0.3073 (W)+22.148. The
relationship between (Si+F) and W therefore seems to be based on composition
rather than structure of available SiHy contact lens materials.
PMID- 29944509
TI - Intrasubject Repeatability and Interdevice Agreement of Anterior Chamber Depth
Measurements by Orbscan and Pentacam in Different Grades of Keratoconus.
AB - OBJECTIVES: To evaluate the repeatability of anterior chamber depth (ACD)
measurements by Orbscan and Pentacam imaging devices in different grades of
keratoconus. METHODS: One examiner performed 3 consecutive ACD measurements with
both devices on 74 eyes of 42 keratoconus patient. Repeatability was assessed
using intrasession test-retest variability. Within-subject SD was determined for
repeatability, and the coefficient of variation was calculated for each
measurement. The intraclass correlation coefficient (ICC) was also determined to
assess the variance of repeated data. RESULTS: Overall, the three ACD
measurements were not significantly different either with Pentacam or Orbscan.
The ICC index values were greater than 90% with both devices, and it
significantly reduced at higher grades of keratoconus with Pentacam. Interdevice
differences were statistically significant. The interdevice agreement with ACD
measurements was 0.981, and the agreement was lower at higher grades of
keratoconus. The 95% limits of agreement between the 2 devices for ACD was from
0.19 to 0.04. CONCLUSIONS: Our results indicate acceptable repeatability for ACD
measurements with both Orbscan and Pentacam in keratoconus patients. The
progression of keratoconus has no significant effect on repeatability results of
these devices. The good agreement between them allows their interchangeable use.
PMID- 29944510
TI - Comparison Between Diclofenac and Ketorolac Ophthalmic Drops for Pain Management
After Photorefractive Keratectomy: A Randomized Clinical Study.
AB - OBJECTIVES: To assess and compare the efficacy of two nonsteroidal anti
inflammatory drugs (NSAIDs), namely diclofenac and ketorolac, for pain control
after photorefractive keratectomy (PRK). METHODS: In this double-masked clinical
study, 60 patients treated bilaterally with PRK were randomly allocated into two
groups. Postoperatively, one group of patients received diclofenac 0.1% drops and
the other group was prescribed ketorolac 0.5% ophthalmic drops in both eyes every
6 hr on the first day and then, no NSAID was applied until the third day. No oral
analgesic drug was used after surgery. Patients completed the Visual Analog Scale
questionnaire to determine the degree of pain and ocular discomfort (tearing,
foreign body sensation, blurred vision, and photophobia) on the first and the
third day after surgery. RESULTS: Pain relief was achieved with both medications
after surgery, and there was no significant intergroup difference in the level of
pain reduction at 24 and 72 hr postoperatively (P>0.05). The ketorolac group
experienced less tearing and photophobia only at 24 hr postoperatively (P=0.01),
and by 72 hr after surgery, the results were similar in two groups (P>0.05).
There was no significant intergroup difference in terms of foreign body sensation
or blurred vision on the first or third postoperative days (P>0.05). CONCLUSIONS:
Both diclofenac and ketorolac are effective in reducing pain and ocular
discomfort after PRK, and ketorolac may have greater control on tearing and
photophobia during the first 24 postoperative hours.
PMID- 29944511
TI - Stabilization Time of Anterior Segment Parameters After Trabeculectomy Surgery.
AB - OBJECTIVES: To investigate the postoperative changes in the anterior segment
parameters by Scheimpflug imaging method in patients undergoing trabeculectomy
surgery. METHODS: This prospective study included 38 phakic eyes of 38 patients
with primary open-angle glaucoma who underwent trabeculectomy. Anterior chamber
angle (ACA), anterior chamber depth (ACD), anterior chamber volume (ACV), and
central corneal thickness (CCT) of the eyes were measured by performing
Scheimpflug imaging in preoperative (baseline) and postoperative periods (1st
week and 1st, 3rd, and 6th months after the surgery). RESULTS: Significant
differences were observed in all the anterior segment parameters during the
postoperative period (P<0.001 for ACA, ACD, and CCT; P=0.001 for ACV). Compared
with preoperative values, ACA, ACD, and ACV values decreased and CCT value
increased in the 1st postoperative week (P<0.001 for all the parameters).
Compared with the 1st postoperative-week values, ACA, ACD, and ACV values
significantly increased and CCT value significantly decreased in the 1st
postoperative month (P=0.002 for ACV; P<0.001 for ACA, ACD, and CCT). However, no
significant differences were observed between the baseline and 1st postoperative
month values (P>0.05 for all the parameters). Moreover, the changes in the
anterior segment parameters were not statistically significant after the 1st
postoperative month. CONCLUSIONS: Our results showed that the changes in the
anterior segment parameters observed in the early postoperative period after
trabeculectomy returned to their baseline values after approximately 1 month
after the surgery and remained stable thereafter.
PMID- 29944512
TI - Office-Based Diagnosis of Demodex Using Smartphone.
AB - Demodex is an important pathogen in ophthalmology. It is believed to cause a
variety of eyelid and eyelash diseases. Currently, light microscopes are being
used for imaging demodex. However, microscopes are not available everywhere.
Also, it is not cost-effective to perform light microscopy in every case. In this
case, we demonstrate a new method: imaging demodex using cell phone. A 90-diopter
noncontact double aspheric lens was attached to the posterior camera of the
smartphone with clear tape. An eyelash of a patient with blepharitis was removed.
A video was taken using smartphone. There was a moving demodex parasite in the
root of the eyelash. A clear video image could be taken using the smartphone. A
smartphone and a 90-diopter lens are adequate for the imaging and diagnosis of
demodex.
PMID- 29944513
TI - The Impact of Sleep Duration on Performance Among Competitive Athletes: A
Systematic Literature Review.
AB - The athletic advantage of sleep, although commonly touted by coaches, trainers,
and sports physicians, is still unclear and likely varies by sport, athletic
performance metric, and length of sufficient or insufficient sleep. Although
recent literature reviews have highlighted circadian and nutritional factors that
influence different aspects of athletic performance, a systematic summary of the
effects of sleep duration and sleep quality on performance among competitive
athletes is lacking. Here we systematically review the relationship between sleep
duration and sleep quality and objective athletic performance among competitive
athletes across 19 studies representing 12 sports. Taken holistically, we find
that the sports requiring speed, tactical strategy, and technical skill are most
sensitive to sleep duration manipulations. Furthermore, longer-term sleep
manipulations are more likely than acute sleep manipulations (whether deprivation
or extension) to affect athletic performance. Thus, the importance of sleep for
competitive athletes to achieve high performance is dependent on the demands of
the sport as well as the length of sleep interventions. In light of the limited
number of studies investigating sleep quality and performance, the potential
relevance of subjective sleep quality remains an interesting question for future
work.
PMID- 29944514
TI - Pseudonormalization of the Typical Electrocardiography Repolarization Pattern of
a Black Athlete.
AB - Cardiac repolarization of black athletes has a distinctive pattern. During an
episode of pericarditis, this pattern may evolve into a "pseudonormalized"
electrocardiography (ECG). On resolution of the pericardial inflammation, the ECG
may return to the normal variant for a black athlete, sounding the alarms of
extended disease to the myocardium. Recognizing the normal variant for a black
athlete will reduce the need for unnecessary further testing or treatments. The
case is discussed in detail.
PMID- 29944515
TI - Novel Factors Associated With Analgesic and Anti-inflammatory Medication Use in
Distance Runners: Pre-race Screening Among 76 654 Race Entrants-SAFER Study VI.
AB - OBJECTIVE: Analgesic/anti-inflammatory medication (AAIM) increases the risk of
medical complications during endurance races. We determined how many runners use
AAIM before or during races, AAIM types, and factors associated with AAIM use.
DESIGN: Cross-sectional study. SETTING: 21.1-km and 56-km races. PARTICIPANTS:
Seventy-six thousand six hundred fifty-four race entrants. METHODS: Participants
completed pre-race medical screening questions on AAIM use, running injury or
exercise-associated muscle cramping (EAMC) history, and general medical history.
MAIN OUTCOME MEASURES: Analgesic/anti-inflammatory medication use, types of AAIM
(% runners; 95% confidence interval), and factors associated with AAIM use (sex,
age, race distance, history of running injury or EAMC, and history of chronic
diseases) [prevalence ratio (PR)]. RESULTS: Overall, 12.2% (12.0-12.5) runners
used AAIM 1 week before and/or during races (56 km = 18.6%; 18.0-19.1, 21.1 km =
8.3%; 8.1-8.6) (P < 0.0001). During races, nonsteroidal anti-inflammatory drugs
(NSAIDs) (5.3%; 5.1-5.5) and paracetamol (2.6%; 2.4-2.7) were used mostly.
Independent factors (adjusted PR for sex, age, and race distance; P < 0.0001)
associated with AAIM use were running injury (2.7; 2.6-2.9), EAMC (2.0; 1.9-2.1),
cardiovascular disease (CVD) symptoms (2.1; 1.8-2.4), known CVD (1.7; 1.5-1.9),
CVD risk factors (1.6; 1.5-1.6), allergies (1.6; 1.5-1.7), cancer (1.3; 1.1-1.5),
and respiratory (1.7; 1.6-1.8), gastrointestinal (2.0; 1.9-2.2), nervous system
(1.9; 1.7-2.1), kidney/bladder (1.8; 1.6-2.0), endocrine (1.5; 1.4-1.7), and
hematological/immune (1.5; 1.2-1.8) diseases. CONCLUSIONS: 12.2% runners use AAIM
before and/or during races, mostly NSAIDs. Factors (independent of sex, age, and
race distance) associated with AAIM use were history of injuries, EAMC, and
numerous chronic diseases. We suggest a pre-race screening and educational
program to reduce AAIM use in endurance athletes to promote safer races.
PMID- 29944517
TI - Perioperative Blood Management, Red Cell Recovery (Cell Salvage) Practice in an
Australian Tertiary Hospital: A Hospital District Clinical Audit.
AB - BACKGROUND: Data on red cell recovery (cell salvage) utilization in Australia are
limited and national guidance is based on a single Australian audit conducted at
a hospital that excludes cardiothoracic surgery. This clinical audit aimed to
analyze the utility of red cell recovery at a tertiary health care facility which
includes cardiothoracic surgery. Secondary aims of this study were to identify
specific surgical procedures in which red cell recovery is most beneficial and to
quantify this benefit. METHODS: Data were collected retrospectively on all adult
red cell recovery surgical cases conducted at a 2-campus health care facility
over a 2-year period. Case demographic data, including surgical procedure, red
blood cell return, and hematocrit levels, were collated and analyzed against
national cell salvage guidelines. Average return per procedure was collated into
a red cell recovery benefit analysis. RESULTS: A total of 471 red cell recovery
cases for 85 surgical procedures met inclusion criteria. Of the 7 surgical
subspecialties utilizing red cell recovery, orthopedics utilized the most cases
(22.9%, n = 108), followed by urology (19.1%, n = 90) and cardiothoracic surgery
(18.3%, n = 86). Radical retropubic prostatectomy (11.7%), revision (7.6%), and
primary (6.6%) total hip replacement were the most utilized procedures. Red cell
recovery use had a 79% compliance rate with national guidelines. Vascular surgery
and urology had the highest average return at 699 mL (interquartile range, 351
1127; CI, 449-852) and 654 mL (interquartile range, 363-860; CI, 465-773),
respectively. CONCLUSIONS: Overall, our center demonstrated good compliance with
national red cell recovery guidelines. This audit adds to the existing data on
red cell recovery practice in Australia and provides a benefit-specific surgical
procedure guideline that includes cardiothoracic surgery.
PMID- 29944516
TI - Preoperative High-Dose Methylprednisolone and Glycemic Control Early After Total
Hip and Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.
AB - BACKGROUND: To evaluate the effect of a single preoperative dose of 125 mg
methylprednisolone (MP) on glycemic homeostasis early after fast-track total hip
and knee arthroplasty. METHODS: One-hundred thirty-four patients undergoing
elective unilateral total hip arthroplasty and total knee arthroplasty were
randomized (1:1) to preoperative intravenous MP 125 mg (group MP) or isotonic
saline intravenous (group C). All procedures were performed under spinal
anesthesia, using a standardized multimodal analgesic regime. The primary outcome
was the change in plasma glucose 2 hours postoperatively, and secondary outcomes
included plasma C-peptide concentrations, homeostatic model assessment (HOMA),
HOMA-IR (insulin resistance), and HOMA-B (beta-cell function). Fasting blood
samples were collected at baseline and 2, 6 (nonfasting), 24, and 48 hours after
surgery with complete samples from 122 patients (group MP = 62, group C = 60) for
analyses. RESULTS: MP patients had increased plasma glucose levels at 2 hours
(adjusted mean [95% CI], 7.4 mmol.L [7.2-7.5] vs 6.0 mmol.L [5.9-6.2]; P = .023)
and 6 hours (13.9 mmol.L [13.3-14.5] vs 8.4 mmol.L [7.8-9.0]; P < .001), and in
plasma C-peptide 24 hours postoperatively (1675 pmol.L [1573-1778] vs 1248 pmol.L
[1145-1351]; P < .001). An impaired insulin response was also observed in group
MP as reflected by HOMA-B (P < .001). Additionally, HOMA-IR increased 24 hours
postoperatively in group MP compared to group C (P < .001). Parameters were
normalized 48 hours postoperatively. CONCLUSIONS: Preoperative administration of
MP 125 mg resulted in a transient postoperative increase in plasma glucose and
insulin resistance and impaired insulin secretion in response to hyperglycemia.
PMID- 29944518
TI - Treating Anemia in the Preanesthesia Assessment Clinic: Results of a
Retrospective Evaluation.
AB - BACKGROUND: Perioperative anemia is challenging during hospital stay because
anemia and red blood cell (RBC) transfusions are associated with an increased
morbidity and mortality. With the implementation of patient blood management
(PBM), a preanesthesia assessment clinic to screen and treat anemia before
elective surgery was institutionalized at Muenster University Hospital, Germany.
The main objective of this study was to evaluate the association between treating
preoperative anemic patients with intravenous iron (IVI) and (primarily)
presurgical hemoglobin levels and (secondarily) use of RBCs and mortality.
METHODS: Between April 1, 2014, and July 4, 2016, patients scheduled for elective
surgery with a risk for RBC transfusions >10% in 2013 were screened for
preoperative anemia and, if indicated, treated with IVI. Patients' data, time
span between visit in the anesthesia/PBM clinic and surgery, demographic data,
type of surgery, the difference of hemoglobin levels between visit and surgery,
RBC transfusion, infectious-related International Classification of Disease codes
during hospital stay, and 1-year survival were determined retrospectively by
screening electronic data files. In addition, patients were interviewed about
adverse events, health-related events, and infections via telephone 30, 90, and
365 days after visiting the anesthesia/PBM clinic. RESULTS: A total of 1101
patients were seen in the anesthesia/PBM clinic between days -28 and -1 (median
[Q1-Q3], -3 days [-1, -9 days]) before elective surgery. Approximately 29% of
patients presented with anemia, 46.8% of these anemic patients were treated with
ferric carboxymaltose (500-1000 mg).In the primary analysis, hemoglobin levels at
median were associated with a reduction between the visit in the anesthesia/PBM
clinic and the surgery in all nonanemic patients on beginning of medical
treatment (nonanemic patients at median -2.8 g/dL [-4, -0.9 g/dL], while anemic
patients without IVI presented with median differences of -0.8 g/dL [-2, 0 g/dL]
and anemic patients with IVI of 0 g/dL [-1.0, 0.5 g/dL]). Hemoglobin levels
raised best at substitution 22-28 days before surgery (0.95 g/dL [-0.35, 1.18
g/dL]). Due to the selection criteria, transfusion rates were high in the cohort.
Overall, there was no association between IVI treatment and the use of RBC
transfusions (odds ratio for use of RBCs in anemic patients, no IVI versus IVI:
1.14; 95% confidence interval, 0.72-1.82). Patients treated with or without IVI
presented a comparable range of International Classification of Disease codes
related to infections. Telephone interviews indicated similar adverse events,
health-related events, and infections. Cox regression analysis showed an
association between anemia and reduced survival, regardless of IVI. CONCLUSIONS:
An anemia clinic within the preanesthesia assessment clinic is a feasible and
effective approach to treat preoperative anemia. The IVI supplementation was safe
but was associated with decreased RBC transfusions in gynecology/obstetric
patients only. The conclusions from this retrospective analysis have to be tested
in prospective, controlled trials.
PMID- 29944519
TI - Usefulness of the Korean Version of the CAGE-Adapted to Include Drugs Combined
With Clinical Predictors to Screen for Opioid-Related Aberrant Behavior.
AB - BACKGROUND: As national opioid consumption in South Korea has soared, well
validated screening tools for opioid use disorder (OUD) have become
indispensable. The aims of our study were to evaluate OUD using the Korean
version of the CAGE-Adapted to Include Drugs (CAGE-AID) and the CAGE-Opioid (an
alternative version of the CAGE-AID), and to investigate clinical predictors that
might be useful to screen for OUD in conjunction with the CAGE-AID/Opioid
questionnaires. METHODS: A single-center, prospective, observational study was
performed. After linguistic validation of the Korean version of the CAGE
AID/Opioid questionnaires, we assessed OUD in patients with chronic opioid
treatment. Multivariable logistic models of the CAGE-AID/Opioid questionnaires
combined with relevant clinical predictors were established. Then, the receiver
operating characteristic curve analysis of the multivariable CAGE-AID/Opioid
models was conducted to assess diagnostic accuracy to screen for OUD. Next, we
calculated predicted probability with >85% sensitivity and >50% specificity in
each CAGE-AID and CAGE-Opioid model. Using the optimal value of the predicted
probability, a cutoff score of the CAGE-AID/Opioid questionnaires combined with
the relevant clinical factors was suggested to screen for OUD. RESULTS: Among 201
participants, 51 patients showed >=1 OUDs. In the multivariable regression model,
male sex, comorbid neuropsychiatric disorder, and current heavy drinking
significantly remained as clinical variables to predict OUD combined with the
scores of the Korean CAGE-AID/Opioid questionnaire. The area under the curve was
0.77 (95% confidence interval, 0.71-0.83) for the CAGE-AID model and 0.78 (95%
confidence interval, 0.71-0.83) for the CAGE-Opioid model. The optimal predicted
probability values to screen for OUD in the CAGE-AID/Opioid models were >0.135
(sensitivity, 0.86; specificity, 0.52) and >0.142 (sensitivity, 0.86;
specificity, 0.53), respectively. When we used these predictive probabilities,
the cutoff score of the CAGE-AID/Opioid questionnaires ranged from 0 to 3, which
was dependent on the presence of the relevant clinical variables in each model.
CONCLUSIONS: In this study, one fourth of the total participants with chronic
opioid treatment showed OUD in the Korean population. The multivariable models of
the CAGE-AID/Opioid with sex, comorbid neuropsychiatric disorder, and current
heavy drinking are valid parameters to screen for OUD, with the cutoff scores of
the CAGE-AID/Opioid questionnaires ranging from 0 to 3 depending on the presence
of the clinical variables.
PMID- 29944520
TI - Incidence and Epidemiology of Perioperative Transfusion-Related Pulmonary
Complications in Pediatric Noncardiac Surgical Patients: A Single-Center, 5-Year
Experience.
AB - BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion
associated circulatory overload (TACO) are the leading causes of transfusion
related fatalities. While these transfusion-related pulmonary complications
(TRPCs) have been well detailed in adults, their burden in pediatric subsets
remains poorly defined. We sought to delineate the incidence and epidemiology of
pediatric TRPCs after intraoperative blood product transfusion. METHODS: In this
retrospective cohort study, we evaluated all consecutive pediatric patients
receiving intraoperative blood product transfusions during noncardiac surgeries
between January 2010 and December 2014. Exclusion criteria were cyanotic heart
disease, preoperative respiratory insufficiency, extracorporeal membrane
oxygenation, and American Society of Anesthesiologists physical status VI.
Medical records were electronically screened to identify those with evidence of
hypoxemia, and in whom a chest x-ray was obtained within 24 hours of surgery.
Records were then manually reviewed by 2 physicians to determine whether they met
diagnostic criteria for TACO or TRALI. Disagreements were adjudicated by a third
senior physician. RESULTS: Of 19,288 unique pediatric surgical patients, 411 were
eligible for inclusion. The incidence of TRPCs was 3.6% (95% confidence interval
[CI], 2.2-5.9). TACO occurred in 3.4% (95% CI, 2.0-5.6) of patients, TRALI was
identified in 1.2% (95% CI, 0.5-2.8), and 1.0% (95% CI, 0.4-2.5) had evidence for
both TRALI and TACO. Incidence was not different between males (3.4%) and females
(3.8%; P = .815). Although a trend toward an increased incidence of TRPCs was
observed in younger patients, this did not reach statistical significance (P =
.109). Incidence was comparable across subsets of transfusion volume (P = .184)
and surgical specialties (P = .088). Among the 15 patients experiencing TRPCs,
red blood cells were administered to 13 subjects, plasma to 3, platelets to 3,
cryoprecipitate to 2, and autologous blood to 3. Three patients with TRCPs were
transfused mixed blood components. CONCLUSIONS: TRPCs occurred in 3.6% of
transfused pediatric surgical patients, with the majority of cases attributable
to TACO, congruent with adult literature. The frequency of TRPCs was comparable
between genders and across surgical procedures and transfusion volumes. The
observed trend toward increased TRPCs in younger children warrants further
consideration in future investigations. Red blood cell administration was the
associated component for the majority of TRPCs, although platelets demonstrated
the highest risk per component transfused. Mitigation of perioperative risk
associated with TRPCs in pediatric patients is reliant on further
multiinstitutional studies powered to examine patterns and predictors of this
highly morbid entity.
PMID- 29944521
TI - US Food and Drug Administration Disruption of Generic Drug Market Increases
Hospital Costs.
AB - BACKGROUND: The purpose of the US Food and Drug Administration's Marketed
Unapproved Drugs Initiative is to decrease marketing of older unapproved
medications. The administration has recently extended its rulings by including
sterile injectable drugs administered in the inpatient environment. The impact of
this initiative on the inpatient environment has been minimally studied. METHODS:
Consecutive retrospective purchase data of vasopressin for injection
(vasopressin) and neostigmine methylsulfate for injection (neostigmine) from 720
hospitals and 746 hospitals, respectively, were included. Purchases occurred from
January 1, 2010 to December 31, 2016. The average noncontract drug price was
calculated and compared to the purchase data during the impact of the initiative.
Comparison was made of hospital purchases made before and after the initiative.
The year 2014 was considered a washout transition year due to the large amounts
of discontinued unapproved formulations that were still available and purchased
by hospitals. The analysis was completed using a matched paired t test. RESULTS:
The noncontract price for vasopressin increased from $12.83 per vial to $158.83
per vial (1138% increase) and for neostigmine from $27.74 per vial to $175.14 per
vial (531% increase) across the pre- and postinitiative intervals; however,
purchase volumes after the price increases were not found to have a statistically
significant difference compared to purchases before the price increases (P = .98
and P = .4, respectively). CONCLUSIONS: Health systems have experienced a
significant cost increase of vasopressin and neostigmine and are absorbing price
increases for these older, generic sterile injectable drugs.
PMID- 29944523
TI - Use of Earlier-Reported Rotational Thromboelastometry Parameters to Evaluate
Clotting Status, Fibrinogen, and Platelet Activities in Postpartum Hemorrhage
Compared to Surgery and Intensive Care Patients.
AB - BACKGROUND: Rotational thromboelastometry (ROTEM) can provide clinical
information in 10-20 minutes for guiding administration of fibrinogen, platelets,
and fresh frozen plasma products. While ROTEM testing is well established for
cardiac and other surgeries, it is less characterized for use in postpartum
hemorrhage (PPH) patients. We wanted to determine if the earlier-measured ROTEM
parameters (alpha-angle and amplitude at 10 minutes [A10]) could replace the
later parameters (amplitude at 20 minutes and maximum amplitude [maximum clot
firmness {MCF}]) in all patient groups studied. We also correlated the A10 and
alpha-angle of the EXTEM and FIBTEM tests to the fibrinogen levels and platelet
counts in these patients. METHODS: We retrospectively analyzed 100 sets of EXTEM
and FIBTEM results ordered on patients undergoing operations for PPH, patients in
intensive care units (ICU), and those undergoing cardiothoracic surgery
(cardiothoracic operating room [C/T OR]). We determined if the correlations among
the various parameters were similar among the PPH, ICU, and C/T OR patients.
RESULTS: As expected, the EXTEM A10 (A10EX) and FIBTEM A10 (A10FIB) correlated
highly to the EXTEM MCF and FIBTEM MCF in all patient groups. The A10EX parameter
correlated significantly to both fibrinogen and platelet levels, and the A10FIB
correlated to the fibrinogen levels. The difference between the A10EX and the
A10FIB (PLTEM) is related to platelet activity, and we found that the PLTEM and
platelet count correlated highly for all 100 PPH patients (r = 0.80), C/T OR
patients (r = 0.70), and ICU patients (r = 0.66), despite 4 high platelet counts
with relatively low PLTEM values in the ICU group. The earlier-reported parameter
EXTEM alpha angle (alpha-EX) is an excellent indicator of the A10EX, with an
alpha-EX >=65 degrees (ie, normal) giving a >96% probability that the A10EX was
>=44 mm, and an alpha-EX value below 65 mm giving an 86% probability that the
A10EX was <44 mm. CONCLUSIONS: The correlations among the ROTEM parameters for
the PPH comparisons were equivalent to the C/T OR patients studied, and the A10EX
and A10FIB could replace the MCF results in all patient groups. Also, the alpha
EX was an early indicator of the A10EX and had good correlations to the A10FIB
and the fibrinogen in all patient groups. Finally, in a separate group of 62
comparisons, the FIBTEM alpha angle showed promise as an early indicator of the
A10FIB and the fibrinogen levels.
PMID- 29944524
TI - Ketamine as a Rapid Sequence Induction Agent in the Trauma Population: A
Systematic Review.
AB - The choice of drug used to facilitate endotracheal intubation in trauma patients
during rapid sequence induction (RSI) may have an impact on survival. Ketamine is
commonly used in the hemodynamically unstable trauma patient although it has been
associated with side effects. This review sought to investigate whether ketamine
should be preferred over other induction agents for RSI in trauma patients.
PubMed, Embase, and the Cochrane Library were systematically searched on
September 19, 2016 for studies reporting RSI of adult trauma patients with
ketamine compared with another induction agent (etomidate, propofol, thiopental,
or midazolam). No language restrictions were applied. The primary outcome was 30
day mortality, and secondary outcomes included information on blood transfusions,
length of hospital stay, and hospital mortality. Risk of bias was assessed using
the Cochrane Risk of Bias assessment tool for randomized trials and the Risk of
Bias in Non-Randomized Studies of Interventions for nonrandomized studies of
intervention. A total of 4 studies were included. A cohort study from 1976
compared thiopental (n = 26) with ketamine (n = 14) for RSI in trauma patients.
The primary outcome was number of blood transfusions, and no significant
difference was found. Risk of bias was judged to be serious. A randomized
controlled trial from 2009 compared etomidate (n = 57) with ketamine (n = 47) and
found no significant difference in 28-day mortality (odds ratio [OR], 0.8 [0.4
2.0]). The trial was judged to have a low risk of bias. Two cohort studies from
2015 and 2017 also compared etomidate (n = 116 and n = 526) with ketamine (n =
145 and n = 442). No significant difference in hospital mortality between the
groups was observed (OR, 1.11 [0.38-3.27] and OR, 1.41 [0.91-2.16],
respectively). Both studies were judged to have a moderate risk of bias, thus
excluding the possibility of a meaningful meta-analysis. The study from 2017 also
reported number of units of blood transfused during the first 48 hours after
trauma and length of hospital stay. No significant differences were observed (OR,
1.14 [0.87-1.49] and OR, 1.1 [0.95-1.27], respectively). Extremely few studies
have compared induction agents for RSI in trauma patients. No significant
differences have been found in mortality, length of hospital stay, or number of
blood transfusions after induction with ketamine compared to other induction
agents, but a clinically relevant benefit or harm cannot be excluded.
PMID- 29944525
TI - Delayed Breast Reconstruction on Patients With Upper Extremity Lymphedema: A
Systematic Review of the Literature and Pooled Analysis.
AB - BACKGROUND: Breast cancer-related lymphedema (BCRL) is a debilitating condition
with morbidity, hindered quality of life, and increased health-related costs.
Experimental studies support the use of musculocutaneous flaps for managing
animal models with lymphedema. Although vascularized lymph node transfer (VLNT)
and lymphovenous anastomosis are used to surgically treat patients with
lymphedema, it is not known whether musculocutaneous or adipocutaneous flaps (eg,
delayed autologous breast reconstruction) are effective for treating refractory
upper extremity BCRL. We conducted a systematic review and pooled analysis to
assess the impact of delayed breast reconstruction on developed BCRL. METHODS:
Following PRISMA guidelines, we systematically searched PubMed, Scopus, EMBASE,
and Google Scholar databases for relevant studies published through November 11,
2016. We screened 934 unique articles. Of these, we conducted full-text and
reference screening on 37 articles. We then performed a pooled and sensitivity
analysis using random effects. RESULTS: Eight studies met our inclusion criteria.
One study was a case report; 7 studies were case series with sample sizes ranging
from 3 to 38 patients. According to our pooled analysis 58% of patients reported
improvement after breast reconstruction with or without VLNT. Sensitivity
analysis revealed that 84% (95% confidence interval, 0.74-0.95) of patients who
underwent breast reconstruction and VLNT reported improvement, whereas only 22%
(95% confidence interval, 0.12-0.32) of those who had breast reconstruction alone
reported improvement. CONCLUSIONS: Our review summarizes the current evidence
regarding the effect of delayed breast reconstruction on established lymphedema.
The VLNT component of the autologous breast reconstruction procedures may be the
largest contributing factor leading to lymphedema improvement.
PMID- 29944526
TI - Ceftriaxone-Resistant Aeromonas hydrophila Infection Following Leech Therapy: A
New Resistant Strain.
AB - We report a case of ceftriaxone-resistant Aeromonas hydrophila infection in a 32
year-old man after medicinal leech therapy. The patient underwent a free gracilis
muscle flap for dorsal foot soft tissue reconstruction. Because of persistent
congestion after venous revision, medicinal leech therapy was initiated to aid in
flap salvage. Intravenous ceftriaxone was administered prior to application of
leeches for prophylaxis against A. hydrophila. Leech therapy was discontinued
after 1 week, and ceftriaxone was discontinued 24 hours thereafter. An infection
developed despite being on appropriate antibiotics. Culture sensitivities
indicated that A. hydrophila was resistant to ceftriaxone.
PMID- 29944527
TI - Surgical Refinement Following Free Gracilis Transfer for Smile Reanimation.
AB - IMPORTANCE: Gracilis free muscle transfer is widely regarded as the gold standard
functional smile reanimation in long-standing facial palsy. Although most
patients achieve meaningful oral commissure movement, a subset has suboptimal
aesthetic outcomes due to midfacial bulk or oral commissure malposition. Safe
refinements that do not compromise excursion would be a welcome addition to the
surgical armamentarium for this population. OBJECTIVES: The goal of this study
was to describe surgical approaches to the 3 most common postoperative sequelae
that detract from the final result after gracilis facial reanimation and to
examine how these surgical refinements affect aesthetic outcome, smile excursion,
and quality of life. DESIGN: This was a retrospective case series. SETTING:
Tertiary care center (Massachusetts Eye and Ear Infirmary Facial Nerve Center).
PARTICIPANTS: Of 260 gracilis transfers performed since 2003, meaningful
excursion (>3 mm) but poor aesthetic outcome requiring additional surgery was
noted in 21 patients and was related either to excess muscle bulk (9), resting
inferior malposition of the oral commissure (9), or resting superior/lateral
malposition of the oral commissure (3). INTERVENTION: Specific surgical
interventions to address each of these negative sequelae were developed and
refined, to preserve muscle functionality but eliminate the unsightly feature.
MAIN OUTCOME: Aesthetic status, determined by midfacial symmetry; quantitative
smile excursion; and quality of life (using the FaCE instrument) were measured
before and after revision. RESULTS: Patients who underwent gracilis refinement
directed at either muscle debulking, or gracilis tightening or loosening
experienced significantly improved aesthetics/midfacial symmetry and improved
quality of life with no significant decrease in smile excursion. CONCLUSIONS:
Improved aesthetics and quality of life can be achieved through targeted revision
of the gracilis free tissue transfer, without significant loss of smile
excursion.
PMID- 29944528
TI - Single-Stage Primary Cleft Lip and Palate Repair: A Review of the Literature.
AB - BACKGROUND: Single-stage cleft lip and palate repair is a debated surgical
approach. While some studies have described favorable outcomes, concerns include
the effect on craniomaxillofacial growth and increased risk of complications. To
this date, there has not been a comprehensive appraisal of available data
following combined cleft lip and palate repair. METHODS: An extensive literature
review was performed to identify all relevant articles. The level of evidence of
these articles was graded according to the Oxford Centre for Evidence-Based
Medicine Levels of Evidence Scale. RESULTS: A total of 22 relevant articles were
identified, all of which were retrospective in nature. Patient age at the time of
surgery ranged from 1 month to 10 years, the longest duration of follow-up was 18
years, and the largest study included 106 patients. Review of the literature
shows that overall surgical outcomes following combined cleft lip and palate
repair are encouraging. An increased rate of postoperative fistulas with
associated speech abnormalities in some studies is noteworthy. Importantly, there
is no evidence to suggest an impact on craniomaxillofacial growth, and
psychosocial outcomes and parental satisfaction seem to be improved with single
stage surgery as compared with the staged approach. CONCLUSIONS: Our review shows
overall favorable outcomes associated with combined cleft lip and palate repair.
The limited follow-up time or nature of evaluated outcomes in some studies may
underrepresent the true rate of adverse events, and highlights the need for
additional long-term studies with standardized follow-up. To our knowledge, our
review is the first to evaluate existing data regarding outcomes following
combined cleft lip and palate repair.
PMID- 29944522
TI - Society of Anesthesia and Sleep Medicine Guideline on Intraoperative Management
of Adult Patients With Obstructive Sleep Apnea.
AB - The purpose of the Society of Anesthesia and Sleep Medicine Guideline on
Intraoperative Management of Adult Patients With Obstructive Sleep Apnea (OSA) is
to present recommendations based on current scientific evidence. This guideline
seeks to address questions regarding the intraoperative care of patients with
OSA, including airway management, anesthetic drug and agent effects, and choice
of anesthesia type. Given the paucity of high-quality studies with regard to
study design and execution in this perioperative field, recommendations were to a
large part developed by subject-matter experts through consensus processes,
taking into account the current scientific knowledge base and quality of
evidence. This guideline may not be suitable for all clinical settings and
patients and is not intended to define standards of care or absolute requirements
for patient care; thus, assessment of appropriateness should be made on an
individualized basis. Adherence to this guideline cannot guarantee successful
outcomes, but recommendations should rather aid health care professionals and
institutions to formulate plans and develop protocols for the improvement of the
perioperative care of patients with OSA, considering patient-related factors,
interventions, and resource availability. Given the groundwork of a comprehensive
systematic literature review, these recommendations reflect the current state of
knowledge and its interpretation by a group of experts at the time of
publication. While periodic reevaluations of literature are needed, novel
scientific evidence between updates should be taken into account. Deviations in
practice from the guideline may be justifiable and should not be interpreted as a
basis for claims of negligence.
PMID- 29944529
TI - A Technique for the Prevention of Recurrent Eyebrow Ptosis After Brow Lift
Surgery.
AB - BACKGROUND: Preventing the recurrence of eyebrow ptosis after brow lift surgery
is challenging. We developed a novel technique to maintain elevation of the
eyebrow after brow lift surgery. METHODS: A consecutive sample of patients who
underwent brow lift surgery between June 2014 and June 2016 was divided into 2
groups. Group A underwent resection of excess skin during brow lift surgery;
group B underwent the new eyebrow lift technique, which involved resecting skin
and the lateral part of the orbital orbicularis oculi muscle, elevating the lower
margin of the orbital orbicularis oculi muscle, and suturing it to the orbital
periosteum. Eyebrow height and patient satisfaction were measured preoperatively
and after surgery. RESULTS: This study included 273 patients. Mean follow-up time
was 24.8 months (range, 6-52 months). Brow height was similar in groups A and B
immediately postoperatively (group A: 28.37 +/- 3.02 mm vs group B: 29.21 +/-
2.97 mm) and at 6 months after operation (group A: 26.65 +/- 2.53 mm vs group B:
27.45 +/- 2.77 mm). At 12 months (group A: 22.73 +/- 2.31 mm vs group B: 25.61 +/
2.62 mm) and 24 months (group A: 20.76 +/- 2.22 mm vs group B: 24.74 +/- 3.10
mm) after operation, the amount of brow elevation was significantly greater in
group B. Two patients in group B experienced supraorbital neuralgia after
surgery, which resolved by the 6-month follow-up. At 12 and 24 months after
operation, patients in group B were significantly more satisfied with their
surgery than patients in group A. CONCLUSION: Our novel technique is simple and
effective for preventing recurrent eyebrow ptosis after brow lift surgery.
PMID- 29944530
TI - Management of Incidental Hernia Discovered During Abdominal Contouring in Post
Bariatric Surgery Patients.
AB - PURPOSE: An increase in bariatric surgery has led to a rise in postbariatric
contouring procedures. Despite a comprehensive preoperative assessment, body
habitus in these patients may significantly limit the abdominal exam. Abdominal
contouring procedures typically elevate large portions of the skin and fat off
the abdominal wall, and unexpected hernia may be discovered intraoperatively. No
study to date has characterized such hernia discovery at the time of body
contouring surgery. We reviewed our experience of management of incidental hernia
found during abdominoplasty or panniculectomy after laparoscopic bariatric
surgery. METHODS: Records of all post-bariatric surgery patients undergoing
abdominal contouring procedures between 2007 and 2017 were reviewed to identify
patients with incidental hernias discovered intraoperatively. These patients were
further examined by reviewing operative details, patient-specific factors, and
outcomes. RESULTS: Six hundred eighty-one post-bariatric surgery patients
underwent abdominal body contouring procedures with incidental ventral hernia
discovered in 36 patients (5.3% [45 hernias]). At the time of plastic surgery,
average age was 49 years (range, 25-64 years), and body mass index was 30.7 kg/m
(range 25-43 kg/m). Of 36 patients with incidental hernia, 26 patients (72.2%)
had a single hernia, and the remainder had multiple (27.8%). Mean hernia size was
4.1 cm (range, 0.25-24 cm). Most hernias were located paraumbilical/umbilical
(46.7%) or epigastric (37.8%). Ninety-eight percent of hernias were repaired
primarily (n = 44) by the plastic surgeon, and in 1 case (2%), mesh repair was
performed by a consulting general surgeon. Average follow-up was 1.9 +/- 0.3
years. Only 1 patient (2.8%) developed hernia recurrence after 48 months. Other
postoperative complications included superficial wound healing problems (19.4%),
seroma (16.7%), suture abscess (5.6%), and cellulitis that resolved with
antibiotics (5.6%). CONCLUSIONS: This is the first study to characterize
incidental hernia discovered at the time of body contouring in the post-bariatric
surgery patient. The body contouring surgeon should be aware of this common
finding. Hernias typically discovered during panniculectomy or abdominoplasty
arise in umbilical or epigastric regions, likely from prior laparoscopic port
sites, and can be safely repaired by the plastic surgeon with low overall
complication rates.
PMID- 29944531
TI - Optimal Reconstruction Method for Large Radionecrosis Following Breast Cancer
Treatment: Utility of Free Transverse Rectus Abdominis Myocutaneous Flap Using
Contralateral Internal Mammary Artery as Recipient.
AB - INTRODUCTION: In extensive radionecrosis following radiotherapy for breast cancer
(BC) treatment, the defect after excision can be reconstructed with a transverse
rectus abdominis myocutaneous (TRAM) flap. In this study, we report outcome of
free TRAM flap using contralateral internal mammary artery (IMA) as a recipient
in comparison with pedicled TRAM. METHODS: We reviewed cases of chest wall
radionecrosis following BC treatment during the past 8 years. Radionecrosis
involving full-thickness soft tissue with defect sizes greater than 10 * 10 cm
were included. We compared the outcomes of patients who underwent reconstruction
with either pedicled TRAM flaps or free TRAM flaps. We used IMA as a recipient
for free TRAM flap, whereas we used contralateral superior epigastric artery
based flap for pedicled TRAM. RESULTS: A total of 14 BC patients underwent chest
wall reconstruction due to radionecrosis: 7 received pedicled TRAM flaps, 5
received free TRAM flaps, and 2 were excluded because of the small defect size.
The pedicled and free TRAM groups were similar in patient demographics and defect
size. However, distal flap loss rate was significantly higher in the pedicled
TRAM group compared with the free TRAM group (P = 0.028). There was no difference
in abdominal hernia incidence between the 2 groups (P = 0.100). CONCLUSIONS: Wide
chest wall defects caused by radionecrosis following BC treatment can be
successfully reconstructed with a free TRAM flap that uses a contralateral IMA as
a recipient. The free TRAM flap demonstrates a lower rate of distal flap loss
than the pedicled TRAM flap, hence reduces the risk of severe morbidity.
PMID- 29944532
TI - Publication Rates and Author Characteristics From 3 Plastic Surgery Journals in
2006 and 2016.
AB - BACKGROUND: Areas of surgical care in which, traditionally, plastic surgeons were
exclusively involved are now routinely offered by other surgical specialists.
Whether this shift in clinical responsibilities influenced publication rates of
plastic surgeons remains unknown. The current article investigates the proportion
of contributions in plastic surgery journals originating from authors with a
plastic surgery background as well as publication rates and author demographics.
METHODS: A cross-sectional sample study of every publication originating from
Annals of Plastic Surgery, Journal of Plastic, Reconstructive and Aesthetic
Surgery, and Plastic and Reconstructive Surgery was performed for 2006 and 2016.
Data about the articles' methodological design and branch of plastic surgery as
well as authors' country of origin, educational degree and specialty training
were analyzed. RESULTS: From 1721 publications included, head and neck
reconstruction was the branch of plastic surgery with the highest number of
publications at 18% and most articles (30%) were retrospective cohort studies.
From 3381 authors analyzed, a significant proportion originated from United
States (34%). More than 85% of authors were physicians as opposed to other health
care professionals. The specialty with the highest representation was plastic
surgery at 72%, but the proportion decreased in all 3 journals by a mean rate of
3.8% in 2016. CONCLUSIONS: A slight decrease in publication rates from plastic
surgeons occurred in Annals of Plastic Surgery, Journal of Plastic,
Reconstructive and Aesthetic Surgery, and Plastic and Reconstructive Surgery from
2006 to 2016. Publications rates and author characteristics in plastic surgery
journals provide valuable insight on plastic surgeons' contribution to
contemporary scientific literature.
PMID- 29944533
TI - Discussion: A Matter of a Conundrum: Evaluating the Impact of Resident
Participation and the July Effect on Outcomes in Autologous Breast
Reconstruction.
PMID- 29944534
TI - A Modification of an Established Method of Intercalary Extremity Bone Defect
Reconstruction: The "Hemi-Capanna" Technique.
AB - BACKGROUND: Skeletal reconstruction of segmental defects of the appendicular
skeleton is among the most challenging tasks in reconstructive surgery. A popular
method of reconstruction of large osseous defects is the combination of massive
allografts and vascularized bone transfer. We present and discuss our experience
with a modification of the traditional Capanna technique in which the allograft
is split in half longitudinally to provide for more space for postoperative
fibula hypertrophy. METHODS: Patients who underwent reconstruction of segmental
intercalary defects of the tibia using our modified technique were
retrospectively identified. The following parameters were retrieved: patient age,
race, sex, length of skeletal defect, recipient vessels, type of microsurgical
anastomosis, union rate, complication rate, ambulation (yes/no), and follow-up
(in months). RESULTS: Two male patients underwent reconstruction of the tibia via
the modified "hemi-Capanna" technique. The tibia defect measured 12 and 13 cm,
respectively. No intraoperative or postoperative complications were encountered.
Osseous union was obtained in both patients who are both ambulatory. CONCLUSION:
The hemi-Capanna technique not only leaves more room for hypertrophy of the
vascularized fibula, but also simplifies the technique of combining an allograft
with vascularized bone transfer in reconstructions of segmental skeletal defects
of the appendicular skeleton.
PMID- 29944535
TI - The SPEED score in the emergency department: not so fast!
PMID- 29944536
TI - The SPEED score: give it some time.
PMID- 29944537
TI - Supporting Our Residents: A Time for Vision and Voice.
PMID- 29944538
TI - The Public Service Loan Forgiveness Program Should Be Reformed, Not Eliminated.
PMID- 29944539
TI - How an Off-Course Discussion Can Lead to Co-Learning for Both Teachers and
Learners.
PMID- 29944540
TI - Concrete Steps for Empowering Learners to Create a Feedback Environment.
PMID- 29944541
TI - Aligning Health Care and Academia: The Clinician Innovator.
PMID- 29944542
TI - Physician-Scientists: Medical Gladiators in the Arenas of Medicine and Science.
PMID- 29944543
TI - Confronting the Research Funding Crisis: Medical Societies' Role in Filling the
Gap.
PMID- 29944544
TI - Missed Opportunities for Chronic Disease Education in the Longitudinal Primary
Care Clerkship?
PMID- 29944545
TI - Artist's Statement: The Heart of Science and Art.
PMID- 29944546
TI - Who's With Me?
PMID- 29944548
TI - The Music of Medicine.
PMID- 29944547
TI - The Impact of Premedical Clinical Experience.
PMID- 29944549
TI - Commentary on The Music of Medicine.
PMID- 29944550
TI - Osteotomy in Genioplasty by Piezosurgery.
AB - BACKGROUND: The chin is the most prominent and median sector of the lower third
of the face giving harmony to nose and lips. The authors present the application
of piezoelectric scalpel for the correction of different chin deformities. The
distinctive characteristics of this device allow us to avoid or reduce the
immediate genioplasty complications. METHODS: Fifty-five patients with defective
chin have been treated from January 2006 to April 2008. Intraoral chinplasty was
performed during the correction of dentofacial dysmorphisms or associated with
nasal surgery. The authors used a piezoelectric cutting device to perform
different osteotomies and if necessary, interpositional graft was used to
stabilize bony segments. RESULTS: Piezosurgery has been associated with a fewer
number of postoperative complications, especially as regard intraoperative
bleeding, nerve injuries (immediate and late), hematomas and seromas, and
asymmetry (immediate and early). The mean time for completing the complete
procedure of genioplasty with piezosurgery was almost the same compared with the
saw and drill. CONCLUSIONS: Chinplasty represents one of the most common
ancillary procedures and may be associated with corrective surgery of dentofacial
dysmorphisms. Mental nerve injuries, asymmetries, intraoperative bleeding are the
main immediate complications of genioplasty. Distinctive characteristics of
ultrasonic piezoelectric osteotomy are selective cut of mineralized structure
with less risk of vascular and nervous damage (microvibrations), intraoperative
precision (thin cutting scalpel and no macrovibrations), blood free site
(cavitation effect). In our experience, piezoelectric scalpel, compared with saw
and drill, enables us to reduce or avoid immediate complications of chin surgery,
helping the surgeon to reach patients' satisfaction. LEVEL OF EVIDENCE: IV.
PMID- 29944551
TI - Bilateral Harvesting of a Fibula Free Flap: Assessment of Morbidity.
AB - PURPOSE: To investigate morbidity related to harversting of bilateral fibula free
flap for head and neck reconstruction using subjective and functional tests.
METHODS: Patients were retrospectively evaluated using point evaluation system
(PES) and balance evaluation systems test (BESTest) questionnaires to assess
morbidity related to surgery. RESULTS: Five patients were enrolled in the study.
Mean PES scores was 22.2 over 24. Mean overall function assessed with BESTest was
77.6%, and the results were poorest for section I. Sections V and VI had scores
of 88% and 83%, respectively, indicating that the sensory balance and gait
stability of the patients were compromised only minimally. CONCLUSION: Bilateral
harvesting of the fibula free flap is not associated with an increase in long
term morbidity and does not lead to significant functional impairments.
Therefore, this procedure should be considered safe, and can be performed without
concern regarding morbidity, when bone reconstruction with a fibula free flap is
indicated.
PMID- 29944552
TI - Jugular Bulb Anatomy for Lateral Skull Base Approaches.
AB - BACKGROUND: This study was designed to define the detailed anatomical relations
of the jugular bulb with the facial nerve, sigmoid sinus, otic capsule, and
internal acoustic canal allowing the safe management of the jugular bulb.
METHODS: Thirty-five formalin-perfused cadaveric temporal bones that had well
mastoid and petrous pneumatization without any neurovascular variations on
computed tomography scan were selected for the study. The bones were dissected
via translabyrinthine approach. RESULTS: The dome of the jugular bulb was located
under the facial nerve in 21 of the cases (60%), in the mastoid cavity in 8 of
the cases (22.9%), and in the tympanic cavity in 6 of the cases (17.1%).
Significant difference was observed only between the temporal bones in which the
dome of the jugular bulb was located in the mastoid cavity and under the facial
nerve with regard to the mastoid cortex-lateral semicircular canal measurement (P
= 0.04). CONCLUSION: Because of the high variability of the position of the dome
of the jugular bulb, the precise knowledge of the relations of the jugular bulb
and the preoperative radiologic verification of possible variations are essential
to avoid the problems associated with its position and to decide the approach
individually.
PMID- 29944553
TI - Evaluation of Airway Volume in Cleft Lip and Palate Following Nasoalveolar
Molding.
AB - Patients with cleft lip and palate (CLP) have commonly reduced nasal airways and
are more prone to snoring, mouth breathing and hypopnea during sleep. Therefore,
the morphometric evaluation of pharyngeal airway in patients with CLP is crucial.
The purpose of this study is to evaluate the pharyngeal airway volumes of
patients with CLP who underwent nasoalveolar molding (NAM) and to compare them
with a well-matched control group without NAM. The study consisted of 40 patients
with CLP divided into 2 main groups (26 with NAM; 14 without NAM) and 4 subgroups
(15 unilateral CLP [UCLP] with NAM, mean age: 10.13 +/- 1.30 years; 11 bilateral
CLP [BCLP] with NAM, mean age: 10.55 +/- 1.51 years; 7 UCLP without NAM, mean
age: 9.86 +/- 1.68 years; 7 BCLP without NAM, mean age: 10.28 +/- 1.89 years).
Nasopharyngeal, oropharyngeal, and total airway volumes of all the patients were
calculated 3-dimensionally with cone-beam computed tomography. There were
statistically significant differences in nasopharyngeal volume (P < 0.05) of NAM
group compared to control group; however, volumetric differences in oropharyngeal
and total pharyngeal airway were not significant (P > 0.05). The amount of
nasopharyngeal, oropharyngeal, and total pharyngeal airway size in the BCLP with
NAM group was significantly larger compared to BCLP without NAM group (P < 0.05).
However, UCLP did not show any significant difference in NAM group (P > 0.05).
This study implies that NAM can effectively enlarge the nasopharyngeal airway
size in patient with CLP. In addition, the pharyngeal airway volume enlargement
is more apparent in BCLP than UCLP individuals.
PMID- 29944554
TI - Correcting the Cleft Lip Nose Deformity: The Graft Number 1 for the Columella.
AB - BACKGROUND: The nose deformity associated with cleft lip is difficult to solve in
the primary and secondary surgery. In an adult patient, many techniques are used
including mobilization, suspension, fixation and trimming the alar cartilages,
septoplasty, nasal bones osteotomies, and dorsal bone and cartilage resection.
Different types of cartilage grafts are commonly used. METHODS: A septal
cartilage graft was used in 75 adult patients with mild to severe cleft lip
deformities. Based on the golden ratio proportions of the columella that can be
observed in the lateral view, a septal cartilage graft with a number 1 shape was
created and inserted between the medial cruras in 75 patients, with unilateral or
bilateral cleft lip, between 2007 and 2014. Complementary surgery was done in the
nose of all the patients. A retrospective, observational, and descriptive study
was made with presurgical and postsurgical photographs, throughout a 6-month
follow-up period. RESULTS: Excellent cosmetic and functional results were seen,
especially in the lateral view. There was 1 septal perforation reported. The
patients were satisfied with the aesthetic results. CONCLUSION: The graft number
1 works in the reality; it has proven to be a stable support to the affected
cartilage, projects a nice nasal tip, and is a lasting solution for adults.
PMID- 29944555
TI - Homologous Banked Bone Grafts for the Reconstruction of Large Cranial Defects in
Pediatric Patients.
AB - PURPOSE: Autogenous bone represents the best material in pediatric reconstructive
cranioplasty because of its compatibility with growth; however, its availability
is limited. Alternative use of alloplastic materials would have the advantage of
unlimited amount, but shows an increased risk of complications and
incompatibility with growth. Fresh frozen banked cadaveric bones could be ideal
for the reconstruction of large cranial defects in growing patients, because it
offers unlimited amount of structural grafts with biomechanics properties quite
similar to the autologous bones. RESULTS: The authors report 2 cases of growing
patients (13 months female and 9 years old male) undergoing the reconstruction of
large (about 70 cm and 50 cm respectively) cranial vault defects, by using
structural homologous banked bone grafts.Analytic main reconstruction materials
risks/benefits evaluation, literature review of few previously reported pediatric
cranioplasty with homologous bone, and both clinical cases satisfactory
radiologic long-term results (beyond 4 years of F.U.) are reported. CONCLUSION:
Structural homologous banked bone grafts appear as a valid solution for pediatric
canioplasty reconstruction of wide defects, entailing the advantages of available
without limitations and compatibility with future growth. The risk of
transmissible infections seems minimal and is totally counterbalanced by the
stability of long-term results.
PMID- 29944556
TI - Long-Term Results for a One-Stage Surgery Technique for Patients With
Craniofacial Plexiform Neurofibroma.
AB - BACKGROUND: Neurofibromatosis (NF) is an autosomal dominant genetic disorder, and
NF type 1 (NF1) is one of the most common forms. Plexiform neurofibroma (PNF) is
one of the characteristic expressions of NF1. The proper treatment for patients
with craniofacial PNF is surgery. The evaluation methods for the surgical outcome
of these patients are still controversial. As a consequence, a one-stage surgical
technique and an appropriate evaluation method for patients with craniofacial PNF
were discussed in this article. METHODS: This research is a retrospective study.
Nine patients with craniofacial PNF were included in this study. They had
undergone a one-stage surgical technique of tumor debulking and nasolabial fold
reconstruction. Three methods had been applied to evaluate the surgical outcome.
RESULTS: Significant improvement was observed in 8 patients. Eight patients were
assessed by the relatively objective evaluation method. Obvious symmetry
improvement was calculated using Mimics software in 7 patients. CONCLUSION: The
surgical technique could achieve good surgical outcomes in both functional and
cosmetic terms. Additionally, the relatively objective evaluation technique based
on Mimics software could be a more convincing method for evaluating the surgical
outcomes of craniofacial patients with PNF.
PMID- 29944557
TI - Comparative Analysis of the Efficacy of Dental Plaque Removal Between Manual and
Powered Toothbrushes in Individuals With Syndactyly.
AB - OBJECTIVE: To compare the efficacy of dental plaque removal between manual and
powered toothbrushes in individuals with syndactyly. MATERIAL AND METHODS:
Seventeen patients with Apert syndrome aged 11 to 30 years. The efficacy of
toothbrushing was evaluated by the O'Leary plaque index at 2 periods: initial
(before toothbrushing) and final (immediately after toothbrushing), using manual
toothbrush (Colgate Twister) and powered toothbrush (Colgate Actibrush). Means
were compared by the ANOVA test at a significance level of 5%. RESULTS: The
reduction in the plaque index was different for each type of toothbrush
(interaction factor between manual and powered toothbrushes and initial and final
periods, P = 0.026). The powered toothbrush provided greater reduction of dental
plaque than the manual toothbrush. CONCLUSION: In individuals with syndactyly,
both manual and powered toothbrushes allowed significant plaque reduction on
tooth surfaces; however, the powered toothbrush exhibited greater efficacy of
plaque removal compared with the manual toothbrush.
PMID- 29944558
TI - Successful Treatment of Pneumocephalus Using a Free-Style Chimeric Free Flap From
a Scarred Thigh.
AB - Pneumocephalus is an air collection in cranial cavity caused by accidental
exposition of intracranial compartment after trauma or surgery. Skull base
reconstruction with free flap is a useful surgical tool to avoid cerebral
herniation or intracranial infection. The authors describe a patient of
pneumocephalus following anterior skull base meningioma resection, unsuccessfully
treated with 2 attempts of fascia lata grafts harvested from both thighs. A free
style chimeric anterolateral thigh free flap was performed using middle third of
rectus femoris muscle to fill the planum spheno-ethmoidalis defect and
adipocutaneous paddle for postoperative monitoring and for favoring a tension
free skin closure. Free-style dissection with limited undermining in the
previously scarred thigh was performed to avoid donor-site complication.
Postoperative course was uneventful with complete resolution of the
pneumocephalus.
PMID- 29944559
TI - Introducing the Rectus Fascia Scalp Augmentation Technique: A New Method for
Improving Scalp Durability in Cranioplasty Reconstruction.
AB - OBJECTIVE: Patients with cranioplasty in need of skull reconstruction are at
increased risk of complications when presenting with abnormally thin scalps. As
such, the authors sought to develop and investigate a new technique for scalp
augmentation using autologous rectus fascia grafts (ARFGs) for prevention of
implant extrusion and long-term scalp durability. METHODS: A retrospective review
of our database, consisting of 450 consecutive cranial reconstructions from 2012
to 2017, was performed under institutional review board approval. Selection
criteria included all adult patients requiring implant-based cranioplasty
reconstruction and concomitant scalp augmentation using ARFGs. All long-term
outcomes were reviewed for scalp-related complications and are presented here.
RESULTS: In total, 12 consecutive patients receiving ARFGs were identified.
Average follow-up was 10 months (range = 2-17 months). Average graft size and
dimension was 82 cm (range = 12-360 cm). All patients (n = 12) underwent
concomitant cranioplasty reconstruction and had a history of at least 5 or
greater previous neurocranial operations. Six patients had radiation therapy
prior to cranioplasty. Two major complications (2/12, 17%) were identified
related to deep, recurrent intracranial infections. More importantly, none of the
patients (n = 12) in this study cohort developed scalp breakdown and/or implant
extrusion in the areas of rectus fascia scalp augmentation. CONCLUSION: The use
of ARFGs for underlay scalp augmentation appears to be both safe and reliable
based on our preliminary experience. This new approach is extremely valuable when
performing large-size cranioplasty reconstruction in patients with abnormally
thin scalps, an extensive neurosurgical history, and/or suboptimal tissue
quality. Furthermore, this method has been successful in avoiding free tissue
transfer and/or staged tissue expansion as first-line surgery in our complicated
cranioplasty population.
PMID- 29944560
TI - Sphenoid Sinus Mucocele Caused by Complications After Transsphenoidal Pituitary
Surgery.
AB - OBJECTIVE: The purpose of this study was to review the clinical characteristics,
treatment methods, and surgical outcomes of sphenoid sinus mucocele after
transsphenoidal pituitary surgery. PATIENTS AND METHODS: A total of 404 patients
who underwent transsphenoidal pituitary surgery between January 2010 and December
2016 were identified. Among them, 5 patients with sphenoid sinus mucocele were
included in this study. In our hospital, a single-nostril endonasal endoscopic
wide sphenoidotomy is routinely used for pituitary tumor surgery. RESULTS: The
occurrence rate of sphenoid sinus mucocele was 1.2% (5/404). Of the 5 patients, 2
were males and 3 were females. Four lesions (80.0%) were located in the right
sphenoid sinus and 1 lesion (20.0%) was located in the left sphenoid sinus.
Endoscopic marsupialization for sphenoid sinus mucocele was performed under local
anesthesia in all patients. There were no major complications resulting from the
surgical intervention, and there was no recurrence at the time of the last follow
up. CONCLUSION: Sphenoid sinus mucocele after endonasal transsphenoidal pituitary
surgery is an extremely rare complication. Nasal endoscopy and MRI are useful for
diagnosing this lesion. Endoscopic marsupialization is a safe and effective
procedure for sphenoid sinus mucocele after endonasal transsphenoidal pituitary
surgery.
PMID- 29944561
TI - Combined External, Endoscopic, Endonasal-Assisted En Bloc Resection of Malignant
Tumors From the Lacrimal Drainage System.
AB - PURPOSE: The aim of this study is to describe a minimally invasive technique of
en bloc resection of malignant tumors from lacrimal drainage system (LDS).
METHODS: This was a noncomparative, retrospective chart review of the clinical
and pathologic findings of patients presenting with a LDS malignant tumor who
underwent endoscopic prelacrimal recess approach with a small external incision
for en bloc excision of the LDS. RESULTS: A total of 12 patients from April 2010
to July 2017 were reviewed in this study. Of the 12 patients, 7 were males. The
mean age was 51 years (range, 38-66 years), and all cases were unilateral.
Histopathology revealed 3 adenoid cystic carcinomas, 2 squamous cell carcinomas,
2 melanomas, and 1 each of papilloma with carcinoma, papillary squamous cell
carcinoma, mucoepidermoid carcinoma, B-cell lymphoma, and natural killer/T-cell
lymphoma. Epiphora and a mass were the most common presentations. Adjuvant
radiotherapy was given in 6 cases after surgery. Eleven patients remain alive and
mean disease-free survival time was 25 months (range, 3-78 months). Two cases
with malignant melanoma showed recurrence and 1 patient died of metastatic
involvement. CONCLUSION: Endoscopic endonasal approach combined with a small
external incision is efficient method for the management of tumors arising from
the LDS.
PMID- 29944562
TI - Auto-Fluorescence and Histopathologic Evaluation of Medication-Related
Osteonecrosis of the Jaws: Perspectives for Treatment.
AB - Auto-fluorescence (AF) of healthy bone tissue has recently been described. Loss
of AF (LAF) has, on the contrary, been reported in necrotic bone. Further, the
use of LAF as a possible guidance to distinguish viable from necrotic bone during
surgical treatment of osteonecrosis has been proposed. The aim of this study is
to detail 8 patients of medication-related osteonecrosis of the jaws treated
through an AF-guided surgical resection. The authors also provide the
histopathologic description of hypo-fluorescent and hyper-fluorescent bone in
each patient. After removal of necrotic bone block, Er:YAG laser was used for
vaporizing further necrotic bone, up to the detection of strongly hyper
fluorescent bone. Samples of hyper-fluorescent bone were collected around areas
of necrosis. Histopathologic evaluation revealed viable bone tissue in all hyper
fluorescent specimens. On the basis of these data, AF-guided surgical resection
could be effective in highlighting surgical margins of necrotic bone tissue and
it might have some utility in a range of applications of bone surgery.
PMID- 29944563
TI - Efficacy of Photocoagulation of Vascular Malformations in the Oral Mucosa Using
Nd: YAG Laser.
AB - The purpose of this study was to analyze the effectiveness of Nd: YAG laser
photocoagulation in the treatment of vascular malformations in the oral and
perioral area; 93 patients (104 lesions) were evaluated in an Ambulatory of Oral
Medicine (2006-2013). The sample consisted of 57 women (61%) and 36 men (39%),
aged 8 to 85 years. The lesion size was smaller than 3 cm in most patients. The
lesions were located on the lips, jugal mucosa, tongue, palate, gingiva, and
retromolar trigone. All patients were treated on an outpatient basis using local
anesthesia and Nd: YAG laser (Power Laser C ) with a wavelength of 1064 nm and a
fiber optic diameter of 400 MUm. After treatment no patients had complications,
however, in patients of deep lesions, 2 or more irradiations were required to
treat the lesions. Finally, the authors conclude that the clinical and aesthetic
satisfactory results of the 93 patients treated with Nd: YAG laser suggest that
this type of laser is effective and safe in the treatment of oral and perioral
vascular malformations.
PMID- 29944566
TI - The Mystery of the Vestibular Labyrinth, a Family Passion.
PMID- 29944565
TI - Review of "National Trends in Readmission Following Inpatient Surgery in the
Hospital Readmissions Reduction Program Era" by Mehtsun WT, Papanicolas I, Zheng
J, Orav EJ, Lillemoe KD, Jha AK in Ann Surg 267: 599-605, 2018.
PMID- 29944564
TI - Fibrous Dysplasia: A Complex Maxillary Reconstruction.
AB - Fibrous dysplasia is a benign tumor of the skeleton. Mostly 2 forms are
described: a monostotic and a poliostotic form. The maxilla and the mandible are
the most interested of the facial district. The authors report a patient of a
huge maxillary fibrous dysplasia. A 63-year-old patient was treated for a 20-year
progressive left maxillary neoformation. A total maxillectomy was performed. The
defect was reconstructed with a custom-made midface implant associated with a
temporal and a pericranial flap.
PMID- 29944567
TI - Cancer-on-a-Chip and Artificial Intelligence: Tomorrow's Cancer Management.
PMID- 29944569
TI - Founding of the Brazilian Association of Apert Syndrome.
PMID- 29944570
TI - Advanced Neuroimaging Techniques for Difficult Diagnoses: Giant Hemorrhagic
Venous Infarct Or Not?
AB - An 51-year-old female presented with a headache, nausea, vomiting, and weakness.
The lesion resembling a hemorrhagic mass was observed in the brain tomography and
magnetic resonance imaging of the patient. However, thrombosis was suspected in
the cerebral venules adjacent to the lesion. Magnetic resonance spectroscopy and
magnetic resonance perfusion data excluded neoplastic lesions. Thus, the patient
was treated for venous infarction. Hemorrhagic venous infarcts may mimic
hemorrhagic masses. For this reason, the distinction of the lesions is important
for the treatment procedure. Advanced neuroimaging in lesions resembling
hemorrhagic masses must be performed for accurate diagnosis.
PMID- 29944568
TI - Serious Complications After Le Fort III Distraction Osteogenesis in Syndromic
Craniosynostosis: Evolution of Preventive and Therapeutic Strategies.
AB - BACKGROUND: There is a paucity of studies that report complication rates
following a subcranial Le Fort III advancement using distraction osteogenesis.
The purpose of this study was to identify and describe serious postoperative
complications following Le Fort III advancement with distraction osteogenesis,
and provide strategies to assist in the resolution of these complications.
METHODS: An observational retrospective study was performed on consecutive
patients with Apert, Crouzon, or Pfeiffer syndromes (n = 16) who underwent Le
Fort III advancement using distraction osteogenesis between 2008 and 2017.
Serious complications were defined as frontal bone loss, cerebrospinal fluid
leak, meningitis, seizures, or major blood loss (ie, massive transfusion within
the first postoperative day). RESULTS: Three (18.7%) patients presented serious
complications, namely cerebrospinal fluid leak (n = 1; 6.2%), seizures (n = 1;
6.2%) due to a halo-type device trans-pin intracranial migration, and major blood
loss (n = 1; 6.2%). Adopting well-delineated interventions, all of these
complications were resolved without fatality. CONCLUSION: A Le Fort III
advancement has a significant morbidity rate, with 3 of our patients (18.7%) in
this study presenting serious complications. Appropriate management reduced this
morbidity, and all complications were resolved without fatality.
PMID- 29944571
TI - Effectiveness of Nasoalveolar Molding in the Unilateral Cleft Lip and Cleft
Palate.
AB - BACKGROUND: Cleft lip and palate develops during embryogenesis due to an
alteration in the fusion of the tissues which will form the upper lip and palate.
The rate of occurrence in Chile is 1.6 per 1000 live births. The object of the
present study was to determine the effectiveness of the Grayson nasoalveolar
molding appliance in reducing the gap between the alveolar segments in cases of
unilateral cleft lip and palate by sex, age at start of treatment, initial gap
between the alveolar segments, and number of checkups. METHODS: The study design
was quasi-experimental, with measurements taken before and after surgery and no
control group. The authors studied the medical records and models of a sample of
52 patients with complete unilateral cleft lip and palate who were discharged
after treatment using Grayson nasoalveolar molding appliance. Treatment was
considered effective when the final gap was 3 mm or less. Then the percentage of
cases in which treatment was effective, applying statistical tests, including log
regression, to assess the influence of other variables was calculated. RESULTS:
The authors observed that the Grayson nasoalveolar molding appliance was
effective in 69.23% of patients. Of the variables studied, the initial gap
presented statistically significant differences (initial gap of 8-12 mm,
effectiveness 82.61%); in the log regression, the same variable presented a
statistically significant difference in the adjusted odds of effectiveness.
CONCLUSION: Grayson nasoalveolar molding appliance presents good effectiveness in
reducing the gap between the alveolar segments in patients with unilateral cleft
lip and palate, especially in cases with a gap of 8 to 12 mm.
PMID- 29944572
TI - From the Editor.
PMID- 29944573
TI - Prioritization, Development, and Validation of American Association of
Cardiovascular and Pulmonary Rehabilitation Performance Measures.
AB - BACKGROUND: In 2014, the American Association of Cardiovascular and Pulmonary
Rehabilitation Quality of Care Committee was asked to develop performance
measures (PMs) to assess program quality and aid in program improvement and
certification. METHODS: A 3-step process was used to prioritize, develop, and
then validate new PMs for both cardiac and pulmonary rehabilitation programs.
First, we surveyed national leadership, medical directors, and program directors
to identify and rank various American Association of Cardiovascular and Pulmonary
Rehabilitation potential PM topics. Then, the face validity of the drafted PMs
was assessed in a second national survey. Finally, we assessed the inter- and
intrarater reliability and feasibility of each PM by abstracting patient charts
at programs throughout the United States. At each step, modifications were made
to refine and improve the measures for clarity, reliability, and consistency.
RESULTS: Through survey answers received from 302 people (19% response rate), we
identified 5 categories for PM development: optimal blood pressure control,
tobacco use cessation, and improvement in functional capacity, depression, and
sensation of dyspnea. After drafting the PMs, a second survey with 82 respondents
(57% response rate), found that the proposed PMs had good face validity. Finally,
we found excellent inter- and intrarater reliability for the blood pressure,
functional capacity, depression, and dyspnea measures (kappa generally >0.80.)
However, validity concerns were raised about the tobacco intervention PM as
written, and it continues to undergo further refinement and testing. CONCLUSIONS:
We developed and validated 5 new PMs for use in cardiac and pulmonary
rehabilitation program quality assessment, improvement, and certification.
PMID- 29944575
TI - Safe and Effective Endoscopic Resection of Massive Colorectal Adenomas >=8 cm in
a Tertiary Referral Center.
AB - BACKGROUND: Endoscopic resection of large colorectal lesions is well reported and
is the first line of treatment for all noninvasive colorectal neoplasms in many
centers, but little is known about the outcomes of endoscopic resection of truly
massive colorectal lesions >=8 cm. OBJECTIVE: We report on the outcomes of
endoscopic resection for massive (>=8 cm) colorectal adenomas and compare the
outcomes with resection of large (2.0-7.9 cm) lesions. DESIGN: This was a
retrospective study. SETTINGS: The study was conducted in a tertiary referral
unit for interventional endoscopy. PATIENTS: A total of 435 endoscopic resections
of large colorectal polyps (>=2 cm) were included, of which 96 were >=8 cm. MAIN
OUTCOME MEASURES: Outcomes included initial successful resection, complications,
recurrence, surgery, and hospital admission. RESULTS: Endoscopic resection was
successful for 91 of 96 massive lesions (>=8 cm). Mean size was 10.1 cm (range, 8
16 cm). A total of 75% had previous attempts at resection or heavy manipulation
before referral. Thirty two were resected using endoscopic submucosal dissection
or hybrid endoscopic submucosal dissection and the rest using piecemeal
endoscopic mucosal resection. No patients required surgery for a perforation.
Five patients had postprocedural bleeding. There were 25 recurrences: 2 were
treated with transanal endoscopic microsurgery, 2 with right hemicolectomy, and
the rest with endoscopic resection. Compared with patients with large lesions,
more patients with massive adenomas had complications (19.8% versus 3.3%),
required admission (39.6% versus 11.0%), developed recurrence (30.8% versus
9.9%), or required surgery for recurrence (5.0% versus 0.8%). LIMITATIONS: This
was a retrospective study. CONCLUSIONS: Endoscopic resection of massive
colorectal adenomas >=8 cm is achievable with few significant complications, and
the majority of patients avoid surgery. Systematic assessment is required to
appropriately select patients for endoscopic resection, which should be performed
in specialist units. See Video Abstract at http://links.lww.com/DCR/A653.
PMID- 29944576
TI - Patient Perceptions and Quality of Life After Colon and Rectal Surgery: What Do
Patients Really Want?
AB - BACKGROUND: Colorectal surgery outcomes must be accurately assessed and aligned
with patient priorities. No study to date has investigated the patient's
subjective assessment of outcomes most important to them during and following
their surgical recovery. Although surgeons greatly value the benefits of
laparoscopy, patient priorities remain understudied. OBJECTIVE: This study aimed
to assess what aspects of patients' perioperative care and recovery they value
most when queried in the postoperative period. DESIGN: This study is an
exploratory cross-sectional investigation of a defined retrospective patient
population. Enrollees were stratified into subcategories and analyzed, with
statistical analysis performed via chi test and unpaired t test. SETTINGS: This
study was conducted at a single academic medical center in New England. PATIENTS:
Patients who underwent a colorectal surgical resection between 2009 and 2015 were
selected. INTERVENTIONS: Patients within a preidentified population were asked to
voluntarily complete a 32-item questionnaire regarding their surgical care. MAIN
OUTCOME MEASURES: The primary outcomes measured were patient perioperative and
postoperative quality of life and satisfaction on selected areas of functioning.
RESULTS: Of 167 queried respondents, 92.2% were satisfied with their recovery.
Factors considered most important included being cured of colorectal cancer
(76%), not having a permanent stoma (78%), and avoiding complications (74%).
Least important included length of stay (13%), utilization of laparoscopy (14%),
and incision appearance and length (2%, 4%). LIMITATIONS: The study had a
relatively low response rate, the study is susceptible to responder's bias, and
there is temporal variability from surgery to questionnaire within the patient
population. CONCLUSIONS: Overall, patients reported high satisfaction with their
care. Most important priorities included being free of cancer, stoma, and
surgical complications. In contrast, outcomes traditionally important to surgeons
such as laparoscopy, incision appearance, and length of stay were deemed less
important. This research helps elucidate the outcomes patients truly consider
valuable, and surgeons should focus on these outcomes when making surgical
decisions. See Video Abstract at http://links.lww.com/DCR/A596. See Visual
Abstract at https://tinyurl.com/yb25xl66.
PMID- 29944577
TI - How to Insert a Draining Seton Correctly.
AB - INTRODUCTION: Misconceptions exist about the proper way to use draining setons in
the management of anal fistulas. This technical note lays out the principles for
their use. TECHNIQUE: Insertion of draining setons is a prerequisite to
successful management of anal fistulas. The correct technique involves
identification of the correct track and internal opening and drainage of the
track with a silastic seton. This sets the stage for definitive repair after the
inflammation subsides. RESULTS: Three cases are presented to illustrate common
errors made during the insertion of draining setons. CONCLUSIONS: Appropriate
seton drainage of an anorectal fistula is an important part of the ultimate
repair. Correct use of setons minimizes symptoms from the seton itself and
optimizes its effectiveness.
PMID- 29944578
TI - Surgical Techniques for Identification of the Prostate Gland Using the Autonomic
Nerve as a Landmark During Transanal Total Mesorectal Excision: Secure Dissection
of the Male Rectourethral Muscle.
PMID- 29944580
TI - Lymph Node Yield After Neoadjuvant Chemoradiotherapy in Rectal Cancer Specimens:
A Randomized Trial Comparing Two Fixatives.
AB - BACKGROUND: It is widely reported that neoadjuvant chemoradiation reduces lymph
node yield in rectal cancer specimens. Some have questioned the adequacy of
finding >=12 lymph nodes for accurate staging, and fewer nodes were correlated
with good response. Others reported that low lymph node count raises the chance
for understaging and correlates with worse survival. In addition, a few studies
demonstrated that diligent specimen analysis increases lymph node count.
OBJECTIVE: The aim of this study was to compare Carnoy's solution and formalin
concerning lymph node yield in specimens of patients with rectal cancer after
neoadjuvant chemoradiation. DESIGN: This is a prospective randomized trial that
was conducted from 2012 to 2015. SETTINGS: This study was performed in a
reference cancer center in Brazil. PATIENTS: Patients who underwent low anterior
resection with total mesorectal excision after neoadjuvant chemoradiation for
rectal adenocarcinoma were included. INTERVENTION: Rectosigmoid specimens were
randomized for fixation with Carnoy's solution or formalin. MAIN OUTCOME
MEASURES: A total of 130 specimens were randomized. After dissection, the
residual fat from the formalin group was immersed in Carnoy's solution in search
for missed lymph nodes (Revision). RESULTS: The Carnoy's solution group had
superior lymph node count (24.0 vs 16.3, p < 0.01) and fewer cases with <12 lymph
nodes (6 vs 22, p = 0.001). The Revision group found lymph nodes in all cases
(mean, 11.1), retrieving metastatic lymph nodes in 6 patients. It reduced the
formalin cases with <12 lymph nodes from 33.8% to 4.6% and upstaged 2 patients.
Tumor response to neoadjuvant chemoradiotherapy was not associated with lymph
node count. LIMITATIONS: This was a unicentric study. CONCLUSIONS: Compared with
formalin, the Carnoy's solution increases lymph node count and reduces the cases
with <12 lymph nodes. Harvested lymph nodes are missed following routine analysis
and this is clinically relevant. Finding <12 lymph nodes is not a sign of good
response to neoadjuvant chemoradiation (www.clinicaltrials.gov. Unique
identifier: NCT02629315). See Video Abstract at http://links.lww.com/DCR/A694.
PMID- 29944579
TI - Can Endorectal Ultrasound, MRI, and Mucosa Integrity Accurately Predict the
Complete Response for Mid-Low Rectal Cancer After Preoperative Chemoradiation? A
Prospective Observational Study from a Single Medical Center.
AB - BACKGROUND: Patients with locally advanced rectal cancer could be managed by a
watch-and-wait approach if they achieve clinical complete response after
preoperative chemoradiotherapy. Mucosal integrity, endorectal ultrasound, and
rectal MRI are used to evaluate clinical complete response; however, the accuracy
remains questionable. Clinical practice based on those assessment methods needs
more data and discussion. OBJECTIVE: The aim of this prospective study was to
evaluate the accuracy of mucosal integrity, endorectal ultrasound, and rectal MRI
to predict clinical complete response after chemoradiotherapy. DESIGN: Endorectal
ultrasound and rectal MRI were undertaken 6 to 7 weeks after preoperative
chemoradiation therapy. Patients then received radical surgery based on the
principles of total mesorectal excision. Preoperative tumor staging achieved by
endorectal ultrasound and rectal MRI was compared with postoperative staging by
pathologic examination. Sensitivity, specificity, and accuracy of each evaluation
method were calculated. SETTINGS: The study was conducted at a single tertiary
care center. PATIENTS: Patients diagnosed with mid-low rectal cancer by biopsy
between May 2014 and December 2016 were enrolled in this study. RESULTS: A total
of 124 patients were enrolled in this study, and postoperative pathology revealed
that 20 patients (16.13%) achieved complete response (ypT0N0). The sensitivity of
mucosal integrity, endorectal ultrasound, and MRI to predict clinical complete
response was 25%. The specificity of mucosal integrity, endorectal ultrasound,
and MRI was 94.23%, 93.90%, and 93.27%. The combination of each 2 or all 3
methods did not improve accuracy. Regression analysis showed that none of these
methods could predict postoperative ypT0. LIMITATIONS: The sample size is small,
and we did not focus on the follow-up data and cannot compare prognosis data with
previous research studies. CONCLUSIONS: Both single-method and combined mucosal
integrity, endorectal ultrasound, and rectal MRI have poor correlation with
postoperative pathologic examination. A watch-and-wait approach based on these
methods might not be a proper strategy compared with radical surgery after
neoadjuvant therapy. See Video Abstract at http://links.lww.com/DCR/A693.
PMID- 29944581
TI - Diagnostic Accuracy of 3-Dimensional Endoanal Ultrasound in Identifying Perianal
Crohn's Fistulas.
AB - BACKGROUND: Perianal fistulizing Crohn's disease is a challenging clinical
situation that requires proper management. Some features seen on the endoanal
ultrasound can be helpful in discriminating between cryptoglandular and Crohn's
disease fistulas. OBJECTIVE: The aim of this study was to define the diagnostic
accuracy of 3-dimensional endoanal ultrasound in differentiating between Crohn's
disease and cryptogenic fistulas. DESIGN: This was a prospective observational
study. SETTINGS: The study was conducted in the colorectal unit of an IBD
referral center. PATIENTS: Consecutive patients referred for suspected perianal
sepsis from September 2015 to December 2016 were included. INTERVENTIONS: Three
dimensional endoanal ultrasonography was the studied intervention. MAIN OUTCOMES
MEASURES: Sensitivity, specificity, and positive and negative likelihood ratios
of 4 ultrasonographic features (Crohn's ultrasound fistula sign, the presence of
a double track, debris or an abscess within the fistula track, and the maximum
width of the track) in discriminating between cryptoglandular and Crohn's disease
fistulas were calculated. The interobserver agreement for each feature was
quantified. RESULTS: In this study, 158 patients, of whom 33 had a diagnosis of
Crohn's disease, were included. The interobserver agreement was good for all of
the ultrasonographic features. All of these features were more frequent in cases
of Crohn's disease fistulas (p = 0.0001). The maximum width of the fistula track
was highly accurate for discriminating between cryptogenic and Crohn's disease
fistulas (area under the receiver operating characteristic curve = 0.922). The
simultaneous presence of 2 features was suggestive of Crohn's disease fistula. In
particular, the presence of a track width >4 mm in conjunction with either a
double track or the Crohn's ultrasound fistula sign showed very high specificity
(1.00). Conversely, a fistula track width <=3 mm had high sensitivity (0.97).
LIMITATIONS: Patients included in the cryptogenic group might be diagnosed as
having Crohn's disease at follow-up. CONCLUSIONS: The combination of specific
endoanal ultrasonographic features allows for highly accurate discrimination
between Crohn's disease and cryptogenic fistulas. See Video Abstract at
http://links.lww.com/DCR/A619.
PMID- 29944584
TI - What Every Colorectal Surgeon Should Know About Bundled Payments for Major Bowel
Procedures: Where Are We Going?
PMID- 29944582
TI - Histological Comparison of Cold versus Hot Snare Resections of the Colorectal
Mucosa.
AB - BACKGROUND: Delayed postpolypectomy bleeding occurs more frequently after hot
resection than after cold resection. OBJECTIVE: To elucidate the underlying
mechanism, we performed a histological comparison of tissue after cold and hot
snare resections. DESIGN: This is a prospective study, registered in the
University Hospital Medical Information Network (UMIN000020104). SETTING: This
study was conducted at Aizu Medical Center, Fukushima Medical University, Japan.
PATIENTS: Fifteen patients scheduled to undergo resection of colorectal cancer
were enrolled. INTERVENTION: On the day before surgery, 2 mucosal resections (hot
and cold) of normal mucosa were performed on each patient using the same snare
without saline injection. The difference was only the application of
electrocautery or not. Resection sites were placed close to the cancer to be
included in the surgical specimen. MAIN OUTCOME MEASURES: The primary outcome
measure was the depth of destruction. Secondary outcome measures included the
width of destruction, depth of the remaining submucosa, and number of vessels
remaining at the resection sites. The number and diameter of vessels in undamaged
submucosa were also evaluated. RESULTS: All cold resections were limited to the
shallow submucosa, whereas 60% of hot resections advanced to the deep submucosa
and 20% to the muscularis propria (p < 0.001). There was no significant
difference in the width of destruction. The number of remaining large vessels
after hot resections trended toward fewer (p = 0.15) with a decreased depth of
remaining submucosa (p = 0.007). In the deep submucosa, the vessel diameter was
larger (p < 0.001) and the number of large vessels was greater (p = 0.018).
LIMITATIONS: Histological assessment was not blinded to the 2 reviewers. Normal
mucosa was used instead of adenomatous tissue. CONCLUSIONS: Hot resection caused
damage to deeper layers involving more large vessels. This may explain the
mechanism for the reduced incidence of hemorrhage after cold snare polypectomy.
See Video Abstract at http://links.lww.com/DCR/A631.
PMID- 29944583
TI - Revisional and Reconstructive Surgery for Failing IPAA is Associated with Good
Function and Pouch Salvage in Highly Selected Patients.
AB - BACKGROUND: Revisional and reconstructive surgery for IPAA is rare given the high
success of pouch surgery for chronic ulcerative colitis. Limited data exist on
both surgical and functional outcomes in patients with chronic ulcerative colitis
who undergo IPAA revision or reconstruction. OBJECTIVE: This study aimed to
determine the surgical and functional outcome in patients with chronic ulcerative
colitis who undergo IPAA revision or reconstruction. DESIGN: A prospectively
collected surgical database was accessed for this study. SETTING: This study was
conducted at an IBD referral center. PATIENTS: Patients with chronic ulcerative
colitis who underwent IPAA revision or reconstruction were selected. MAIN OUTCOME
MEASURES: The primary outcomes measured were 30-day postoperative outcomes and
long-term pouch function. RESULTS: Eighty-one patients were identified. Original
IPAA was performed for chronic ulcerative colitis (n = 71; 88%) and indeterminate
colitis (n = 11; 12.%), and the most common configuration was a J-pouch (n = 69;
86%) with handsewn anastomosis (n = 41;68%). No independent predictors of 30-day
postoperative complications following reconstructive/revisional surgery were
identified. Pelvic abscesses and Crohn's disease of the pouch were independently
associated with ultimate pouch excision. Median follow-up following
revision/reconstruction was 40 months (range, 1-292 months) during which 15
patients (23%) had pouch failure. The 5- and 10-year pouch survival rates
following revision were 85 +/- 5% and 65 +/- 9% by Kaplan-Meier estimation; age
<30 years was significantly associated with pouch survival. Long-term function (n
= 30; 35%) compared with a matched control cohort of primary IPAA was
characterized by significantly increased daytime bowel incontinence (p = 0.0119),
liquid stool (p = 0.0062), and medication to thicken stools (p = 0.0452).
LIMITATIONS: This was a single-center series, and response rate for functional
data was 35%. CONCLUSIONS: In properly selected patients with a failing pouch,
originally made for chronic ulcerative colitis or indeterminate colitis,
revisional and reconstructive surgery is associated with low complication rates,
high pouch salvage, and acceptable long-term pouch function. See Video Abstract
at http://links.lww.com/DCR/A640.
PMID- 29944585
TI - Outcome After Redo Surgery for Complicated Colorectal and Coloanal Anastomosis: A
Systematic Review.
AB - BACKGROUND: When a colorectal or coloanal anastomosis fails because of persistent
leakage or stenosis, or the anastomosis has to be resected for recurrent cancer,
constructing a new anastomosis might be an option in selected patients. This is a
rare and complex type of redo surgery. OBJECTIVE: The aim of this review was to
evaluate the current literature on redo anastomosis for complicated colorectal or
coloanal anastomosis. DATA SOURCES: A systematic literature search of MEDLINE,
EMBASE, the Cochrane Library, the PROSPERO register, clinicaltrials.gov, and the
World Health Organization International Clinical Trials Registry Platform
database was performed. STUDY SELECTION: Two reviewers independently screened the
available literature. All studies reporting on redo surgery and aiming at
reconstruction of a prior low colorectal or coloanal anastomosis for any
indication were included. MAIN OUTCOME MEASURES: Primary outcome was successful
restoration of continuity. Secondary outcomes were postoperative morbidity,
pelvic sepsis, incontinence, and mortality. RESULTS: Nine studies were included,
comprising 291 patients, of whom 76% had index surgery for colorectal cancer.
Pooled proportions showed an overall success rate of 79% (95% CI, 69-86), with a
pooled incidence of major postoperative morbidity of 16% (95% CI, 10-24). The
pooled pelvic sepsis rate was 16% (95% CI, 9-27), and the pooled surgical
reintervention and readmission rates were 11% (95% CI, 8-17) and 7% (95% CI, 3
15). Five studies reported on incontinence, with a pooled proportion of 17% (95%
CI, 10-26). LIMITATIONS: The limitations of this review are the lack of
randomized controlled trials and high-quality studies, and the small sample sizes
and heterogeneous patient populations in the included studies. CONCLUSIONS: Redo
surgery is a valuable treatment option for the complicated colorectal or coloanal
anastomosis with 79% successful restoration of bowel continuity in the published
literature from experienced tertiary centers.
PMID- 29944586
TI - The Future of Interventional Pulmonology and the Role of the Journal.
PMID- 29944587
TI - EBUS-TBNA for the Diagnosis of Lymphoma: Time to Give In?
PMID- 29944588
TI - Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in the Diagnosis
of Breast Cancer Thoracic Metastases and Detection of Receptor Discordance.
AB - BACKGROUND: Metastasis of breast cancer to mediastinal lymph nodes is common and
biopsy of suspicious lesions can have important diagnostic, prognostic, and
therapeutic implications, particularly with respect to tumor receptor status. Our
aim was to show that endobronchial ultrasound-guided transbronchial needle
aspiration (EBUS-TBNA) can be used for the diagnosis of metastatic breast cancer
and demonstrate reliable receptor evaluation that can result in change of
therapy. METHODS: A retrospective review of consecutive adult patients undergoing
EBUS-TBNA from May 2007 to September 2012 was performed. Data collected for
patients with a history of breast cancer included patient demographics, tumor
pathology, receptor analysis, imaging, and bronchoscopy or surgical results.
RESULTS: Sixty-four patients with a history of breast cancer aged from 31 to 81
years underwent EBUS-TBNA for the evaluation of mediastinal lymphadenopathy of
which 16 patients had not been previously treated for their breast cancer with
systemic therapy. Eighty suspicious lymph nodes were biopsied measuring 0.8 to
3.1 cm in diameter. Fifty-nine (92%) patients had diagnostic cytology for
malignancy or benign lymphoid tissue. Breast malignancy was identified in 33
(52%) patients and 23 (70%) of these had sufficient samples for the evaluation of
estrogen, progesterone, and human epidermal growth factor receptor 2 status.
Overall 48% of the patients with receptors analyzed had discordance between the
primary tumor and metastasis. CONCLUSIONS: EBUS-TBNA is a useful tool for
evaluating mediastinal lymphadenopathy in patients with a history of breast
cancer and can provide information on the concordance of receptors status between
the primary tumor and metastatic sites in the thorax.
PMID- 29944589
TI - Lung Parenchymal and Endobronchial Metastases From Ovarian Carcinoma.
AB - Ovarian cancer is the seventh most common cancer in women and the eighth most
common cause of cancer death in the world with an overall 5-year survival rate of
<50%. (1) The most common age of presentation is at the perimenopausal age group
and two-thirds of them present with advanced stage of disease. (2) Thoracic
metastases occur in up to 50% of patients. Pleural effusion is the most common
presentation of thoracic metastases in these patients, whereas pulmonary
parenchymal metastases, lymphangitis, and nodal involvement are less commonly
reported. (3) Tracheobronchial involvement is rare with few cases reported in
literature. Herewith, we are presenting a case of ovarian cancer in a young
female with both lung parenchymal and endobronchial metastases. Bronchoscopy
revealed endobronchial tumor in right lower lobe bronchus part of which was
covered by yellowish necrotic material. Biopsy showed metastatic ovarian
malignancy complicated by aspergillosis. She was started on oral itraconazole
along with supportive management following which hemoptysis stopped.
PMID- 29944590
TI - Cutting Balloon Dilation for Central Airway Stricture.
PMID- 29944591
TI - A Massive Hemothorax in a Pregnant Woman: Role of Interventional Radiology.
PMID- 29944592
TI - Pneumomediastinum Post EBUS-TBNA in Interstitial Lung Disease.
PMID- 29944594
TI - Sevelamer Aspiration.
PMID- 29944595
TI - Bronchoscopic Management of Endobronchial Tumor in Patient With Hemoptysis and
Acute Myocardial Infarction.
PMID- 29944593
TI - Traumatic Expulsion of Tracheal Rings: An Airway Emergency.
PMID- 29944596
TI - Accessory Cardiac Bronchus: Usual Images to Remember an Unusual Finding.
PMID- 29944598
TI - Transbronchial Lung Cryobiopsy With 2 Bronchoscopes: New Novum New Magna.
PMID- 29944597
TI - Synchronic Diagnosis of Non-Hodgkin Lymphoma and Lung Adenocarcinoma via EBUS
guided TBNA.
PMID- 29944599
TI - Juvenile Bronchopulmonary Fibrosarcoma.
PMID- 29944600
TI - Dermatomal Versus Mixed Somatosensory Evoked Potentials in the Diagnosis of
Lumbosacral Spinal Canal Stenosis.
AB - PURPOSE: The existing literature on the use of dermatomal somatosensory evoked
potentials in lumbosacral spinal canal stenosis is limited. The goal of this
study was to evaluate the role of dermatomal against mixed tibial somatosensory
evoked potential (SEP) as a complementary procedure to imaging studies in the
diagnosis of lumbosacral stenosis. METHODS: Thirty patients with clinically and
radiologically diagnosed lumbosacral stenosis and 20 normal individuals were
enrolled in the study. The study was ethically approved, and informed consent for
participation was provided. All participants underwent bilateral mixed tibial and
dermatomal SEP study of the third (L3), fourth (L4), fifth lumbar (L5), and first
sacral (S1) dermatomes. N45, N25, N20, and N10 tibial SEP waves were measured
from four channels, whereas dermatomal waves were measured from cortical
recording. Peak latency and amplitude of each wave were calculated. RESULTS: The
cutoff value of the dermatomal S1 latency showed the highest sensitivity and
specificity percentages (81.7 and 82.5, respectively), followed by L5 and N25.
N25-N45 interpeak latency showed the lowest sensitivity and specificity. All L5,
S1, L4, and N25 latency cutoff values presented highly significant differences
between affected sides and controls (P < 0.0001), followed by N45 and N20. The
amplitude cutoff values of SEP waves showed equivocal sensitivity and specificity
percentages. CONCLUSIONS: Somatosensory evoked potential studies can be used as a
supplementary test for the diagnosis of lumbosacral stenosis, with the dermatomal
studies being more valuable expressing multiple root abnormalities. S1 dermatomal
wave latency has the highest diagnostic value, followed by L5, N25, and then L4
latencies.
PMID- 29944601
TI - The Association Between Professional Burnout and Engagement With Patient Safety
Culture and Outcomes: A Systematic Review.
AB - OBJECTIVES: In the last 20 years, there have been numerous successful efforts to
improve patient safety, although recent research still shows a significant gap.
Researchers have begun exploring the impact of individual level factors on
patient safety culture and safety outcomes. This review examines the state of the
science exploring the impact of professional burnout and engagement on patient
safety culture and safety outcomes. METHODS: A systematic search was conducted in
CINAHL, PubMed, and Embase. Studies included reported on the relationships among
burnout or engagement and safety culture or safety outcomes. RESULTS: Twenty-two
studies met inclusion criteria. Ten studies showed a relationship between both
safety culture and clinical errors with burnout. Two of 3 studies reported an
association between burnout and patient outcomes. Fewer studies focused on
engagement. Most studies exploring engagement and safety culture found a
moderately strong positive association. The limited evidence on the relationship
between engagement and errors depicts inconsistent findings. Only one study
explored engagement and patient outcomes, which failed to find a relationship.
CONCLUSIONS: The burnout/safety literature should be expanded to a
multidisciplinary focus. Mixed results of the relationship between burnout and
errors could be due to a disparate relationship with perceived versus observed
errors. The engagement/safety literature is immature, although high engagement
seems to be associated with high safety culture. Extending this science into
safety outcomes would be meaningful, especially in light of the recent focus on
an abundance-based approach to safety.
PMID- 29944603
TI - Repetitive Practice With Peer Mentoring to Foster Skill Competence and Retention
in Baccalaureate Nursing Students.
AB - A one-group, repeated-measures study explored the effect of repetitive practice
with peer mentoring on skill competence and retention of vital signs and
auscultation of breath and heart sounds in baccalaureate nursing students. Vital
signs competence significantly increased after repetitive practice with peer
mentoring. Skill competence in vital signs and auscultation of breath and heart
sounds did not significantly change four months after repetitive practice with
peer mentoring. This study suggests that repetitive practice with peer mentoring
may show promise to enhance skill competence and retention; however, more
research is needed to support these findings.
PMID- 29944604
TI - Intermittent Running and Cognitive Performance after Ketone Ester Ingestion.
AB - PURPOSE: Ingestion of exogenous ketones alters the metabolic response to exercise
and may improve exercise performance, but it has not been explored in variable
intensity team sport activity, or for effects on cognitive function. METHODS: On
two occasions in a double-blind, randomized crossover design, 11 male team sport
athletes performed the Loughborough Intermittent Shuttle Test (part A, 5 * 15-min
intermittent running; part B, shuttle run to exhaustion), with a cognitive test
battery before and after. A 6.4% carbohydrate-electrolyte solution was consumed
before and during exercise either alone (PLA) or with 750 mg.kg of a ketone ester
(KE) supplement. Heart rate, RPE, and 15-m sprint times were recorded throughout,
and serial venous blood samples were assayed for plasma glucose, lactate, and
beta-hydroxybutyrate. RESULTS: KE resulted in plasma beta-hydroxybutyrate
concentrations of ~1.5 to 2.6 mM during exercise (P < 0.001). Plasma glucose and
lactate concentrations were lower during KE compared with PLA (moderate-to-large
effect sizes). Heart rate, RPE, and 15-m sprint times did not differ between
trials. Run time to exhaustion was not different (P = 0.126, d = 0.45) between
PLA (mean = 268 s, 95% confidence interval [CI] = 199-336 s) and KE (mean = 229
s, 95% CI = 178-280 s). Incorrect responses in a multitasking test increased from
pre- to postexercise in PLA (mean = 1.8, 95% CI = -0.6 to 4.1) but not in KE
(mean = 0.0, 95% CI = -1.8 to 1.8) (P = 0.017, d = 0.70). CONCLUSION: Compared
with carbohydrate alone, coingestion of a KE by team sport athletes attenuated
the rise in plasma lactate concentrations but did not improve shuttle run time to
exhaustion or 15-m sprint times during intermittent running. An attenuation of
the decline in executive function after exhausting exercise suggests a cognitive
benefit after KE ingestion.
PMID- 29944602
TI - DECREASED RETINAL CAPILLARY DENSITY IS ASSOCIATED WITH A HIGHER RISK OF DIABETIC
RETINOPATHY IN PATIENTS WITH DIABETES.
AB - PURPOSE: To quantify retinal microvascular alterations using optical coherence
tomography angiography in diabetic patients, and to evaluate the accuracy of
decreased vessel density (VD) in predicting early diabetic retinopathy (DR).
METHODS: One hundred and two eyes of 51 diabetic patients and 92 eyes of 46
individuals without diabetes were examined. Duration of diabetes, insulin
therapy, blood pressure, HbA1C, dyslipidemia, axial length, and the presence of
DR were recorded. Retinal VD was measured using optical coherence tomography
angiography. The effect of risk factors on VD and on DR was assessed using
multivariable regression analyzes. RESULTS: Compared with controls, VD was lower
in diabetic patients (P < 0.05) and correlated with diabetes duration (P = 0.02).
Decreased VD was associated with a higher risk of DR (odds ratio: 1.24, P =
0.009) after controlling for systemic and ocular confounding variables. Eyes with
a VD of <50% had an odds ratio of 4.55 (P = 0.003) for DR and an odds ratio of
3.22 (P = 0.03) for decreased visual acuity (<20/25) after controlling for
systemic and ocular confounding factors. CONCLUSION: The risk of DR and vision
loss is substantially higher in eyes with lower VD, suggesting that optical
coherence tomography angiography metrics may serve as prognostic biomarkers for
the prediction of early onset DR.
PMID- 29944605
TI - Complex Terrain Load Carriage Energy Expenditure Estimation Using Global
Positioning System Devices.
AB - INTRODUCTION: Military load carriage can cause extreme energy expenditure (EE)
that is difficult to estimate due to complex terrain grades and surfaces. Global
Positioning System (GPS) devices capture rapid changes in walking speed and
terrain but the delayed respiratory response to movement is problematic. We
investigated the accuracy using GPS data in three different equations to estimate
EE during complex terrain load carriage. METHODS: Twelve active duty military
personnel (age, 20 +/- 3 yr; height, 174 +/- 8 cm; body mass, 85 +/- 13 kg) hiked
a complex terrain trail on multiple visits under different external load
conditions. Energy expenditure was estimated by inputting GPS data into three
different equations: the Pandolf-Santee equation, a recent GPS-based equation
from de Mullenheim et al.; and the Minimum Mechanics model. Minute-by-minute EE
estimates were exponentially smoothed using smoothing factors between 0.05 and
0.95 and compared with mobile metabolic sensor EE measurements. RESULTS: The
Pandolf-Santee equation had no significant estimation bias (-2 +/- 12 W; P =
0.89). Significant biases were detected for the de Mullenheim equation (38 +/- 13
W; P = 0.004) and the Minimum Mechanics model (-101 +/- 7 W; P < 0.001).
CONCLUSIONS: Energy expenditure can be accurately estimated from GPS data using
the Pandolf-Santee equation. Applying a basic exponential smoothing factor of 0.5
to GPS data enables more precise tracking of EE during non-steady-state exercise.
PMID- 29944607
TI - Neuroimaging Before ECT?
PMID- 29944608
TI - Outcomes of patients with a pretransplant history of early-stage melanoma.
AB - A history of melanoma within the preceding 5 years is commonly considered a
contraindication to solid organ transplantation. We investigated how a
pretransplant history of melanoma impacts patient survival and melanoma
recurrence. Institutional Review Board approval was obtained, and Duke's
retrospective database was used to identify 4552 patients who underwent a solid
organ transplant at Duke University from 1 January 2001 to 31 December 2016. Data
with regard to the transplant, melanoma characteristics, rejection episodes, and
survival were recorded. Of 4552 patients who underwent a solid organ transplant,
12 (0.3%) had a history of melanoma before transplant (six with melanoma in situ
and six with stage I disease). The median time between melanoma diagnosis and
transplant was 4.13 years (range: 1.1-13.3 years). The study cohort consisted of
four liver transplants, four lung transplants, one kidney transplant, one heart
transplant, one small bowel transplant, and one multivisceral transplant. At the
median follow-up time of 2.8 years, 10 (83.3%) patients were alive. In
nonmelanoma cohorts, the 3-year survival is 70% for thoracic transplants, 78% for
liver transplants, and 88% for kidney transplants. In well-selected patients with
a history of early-stage melanoma and an appropriate time interval between
melanoma treatment and transplant, post-transplant outcomes are favorable.
PMID- 29944609
TI - Limitation of in-situ arthroscopic fixation for stable juvenile osteochondritis
dissecans in the knee.
AB - : Current treatment algorithms for stable juvenile osteochondritis dissecans
(JOCD) of the knee have not been established. For arthroscopically stable lesion,
in-situ arthroscopic fixation with bioabsorbable pins was introduced as a more
desirable approach because of less surgical morbidity and faster recovery.
However, there is a paucity of literature that concludes on its efficacy. The aim
of this study is to determine the efficacy and limitation of in-situ arthroscopic
fixation on stable JOCD lesion in the knee. Ninety-six patients with 110 affected
knees were reviewed. Subsequently, patients who underwent in-situ arthroscopic
fixation for arthroscopically stable JOCD lesions were grouped for further
analysis. Arthroscopic lesion stability was graded according to the Guhl's
grading system from the surgical description of each lesion. The grade I and II
were defined as 'stable' lesions. The lesion status was also evaluated with the
MRI grading system described by Dipaola in preoperative images retrospectively.
The grade I and II lesions were also defined as 'stable' and more than III as
'unstable'. Clinical outcomes were evaluated by the Lysholm score at the final
office visit. If the patient had a revision surgery, the case was classified as a
complete failure. There were 13 lesions in 13 patients with open physis treated
with in-situ arthroscopic fixation using bioabsorbable pins. In this population,
radiographical lesion status and the Lysholm score were significantly improved in
10 cases (preoperative: 77.5+/-11.2, postoperative: 98.9+/-3.1, P=0.002);
however, we found three revision cases (failure rate, 23%). Of these revision
cases, all lesions were graded as 'unstable' in MRI. In this series, the failure
rate was 23% for in-situ arthroscopic fixation for arthroscopically stable JOCD
lesion of the knee. Because of the potential risk for underestimation of lesion
instability, we strongly suggest that this less invasive approach should be
chosen with great care for the lesion that presents arthroscopically stable, but
as unstable status on MRI. LEVEL OF EVIDENCE: Level IV, case series.
PMID- 29944606
TI - The Psychiatric Neuromodulation Unit: Implementation and Management.
AB - The proven effectiveness of neuromodulation and stimulation techniques for the
management of psychiatric disorders has brought strongly needed innovation in
psychiatry, given the high prevalence and high costs of treatment resistance.
Although evidence-based guidelines in neuromodulation have been implemented to
improve the clinical efficacy, safety, and research procedures, practical
suggestions on how to design a psychiatric neuromodulation unit (PNU) are not
available in the scientific literature. In this contribution, we have combined
the results of a literature search with the suggestions of clinical
psychiatrists, managers, and bioethicists who have had firsthand experience in
building a PNU. Eleven key issues concerning the implementation and management of
a PNU were identified: general context, team composition, environment, basic
technical equipment, clinical versus research activities, target clinical
population, education and training, interdisciplinarity, ethical aspects,
regulatory and reimbursement issues, fund-raising, and partnership development.
Moreover, a business plan comprising pragmatic solutions and recommendations for
designing an efficient PNU was laid out.
PMID- 29944612
TI - Electroencephalography and magnetoencephalography in pain research-current state
and future perspectives.
PMID- 29944613
TI - Potentiation of cortical excitatory transmission in chronic pain.
PMID- 29944611
TI - Cognitive dysfunction and pain: considerations for future research.
PMID- 29944610
TI - VALIDITY AND EFFICACY OF INTERNAL LIMITING MEMBRANE PEELING DURING INITIAL
VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT: VISUAL OUTCOMES IN MACULA
SPARING CASES.
AB - PURPOSE: To compare the visual outcomes and prevalence of epiretinal membrane
(ERM) growth postoperatively between eyes treated with and without internal
limiting membrane peeling during vitrectomy for macula-sparing rhegmatogenous
retinal detachment. METHODS: Fifty-five consecutive cases who underwent
vitrectomy for macula-sparing rhegmatogenous retinal detachment were reviewed
retrospectively. The inclusion criteria were a minimal 6-month follow-up
postoperatively and spectral domain optical coherence tomographic images
available at follow-up. Cases with any pre-existing macular condition possibly
affecting the visual prognosis were excluded. All cases were divided into two
groups: 22 cases without internal limiting membrane peeling (Group 1) and 33
cases with internal limiting membrane peeling (Group 2). The two groups were
compared using the Mann-Whitney U test and Fisher exact test in terms of the best
corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution)
before vitrectomy, postoperative BCVA, and the presence of postoperative ERM
growth. Postoperative BCVA and ERM growth were determined at 6 months, 12 months,
and the last visit. The visual outcomes were also analyzed between cases with and
without postoperative symptomatic ERM growth, which caused visual impairment and
required surgical removal. RESULTS: The mean postoperative BCVAs were 0.00,
0.08, and -0.08 logarithm of the minimum angle of resolution in Group 1, and
0.08, -0.08, and -0.08 logarithm of the minimum angle of resolution in Group 2 at
6 months, 12 months, and the last visit, respectively, and did not differ
significantly between the 2 groups at each time point except for at 12 months (P
= 0.027). An ERM developed in 14 cases in Group 1, 7 of which were symptomatic.
No cases in Group 2 had ERM growth. The prevalence of ERM growth was
significantly (P < 0.001) higher in Group 1 than Group 2. The BCVA was
significantly worse at 6 months (P = 0.011), 12 months (P = 0.003), and the last
visit (P = 0.019) in 7 cases with symptomatic ERMs (median, 0.30, 0.15, and 0.10
logarithm of the minimum angle of resolution, respectively) than in 48 cases
without symptomatic ERMs (median, -0.08, -0.08, and -0.08 logarithm of the
minimum angle of resolution, respectively). CONCLUSION: Internal limiting
membrane peeling did not result in decreased visual acuity postoperatively in
cases with a macula-sparing rhegmatogenous retinal detachment, and the procedure
significantly prevented postsurgical ERM growth. Symptomatic ERMs led to
decreased visual acuity even after surgical removal. These results support the
validity and efficacy of internal limiting membrane peeling for preventing ERM
growth after rhegmatogenous retinal detachment repair.
PMID- 29944614
TI - Corrigendum to postoperative pain treatment after total hip arthroplasty: a
systematic review by Karlsen et al. PAIN 2015;156: 8-30.
PMID- 29944615
TI - Investigating generalizability of results from a randomized controlled trial of
the management of chronic widespread pain: the MUSICIAN study: Erratum.
PMID- 29944616
TI - Incidence, Outcomes, and Long-Term Immune Response to Tuberculosis in Organ
Transplant Recipients.
AB - BACKGROUND: Tuberculosis (TB) is a significant opportunistic infection in solid
organ transplant recipients (SOTR). There are limited data on TB incidence in
transplantation from low prevalence countries as well as on long-term TB specific
immune responses. METHODS: We performed a single-center retrospective review of
SOTR diagnosed with active TB between 2000 and 2015 and further contacted the
available patients for a study of long-term T cell responses using an interferon
gamma (IFN-gamma) release assay and a flow cytometry-based assay. RESULTS: We
identified 31 SOTR with active TB for an incidence of 62 cases/100,000 patient
years. 19/31 (61.3%) patients were diagnosed within the first year after
transplant. Nineteen (61.3%) were born in countries with high TB prevalence and
disseminated disease occurred in 22.6%. No patient had been screened for latent
TB infection pretransplant. The majority of patients received isoniazid and a
rifamycin as part of multidrug regimen. In addition, 13/29 (44.8%) patients
received quinolones. One-year mortality in this population was 19.4%. Eight
patients were available for long-term immune responses. Of these, all had
detectable IFN-gamma response by interferon-gamma release assay testing and 7/8
had detectable TB-specific T cells, primarily central and effector T cell
responses in the CD4 compartment and terminally differentiated T cells in the CD8
compartment. CONCLUSIONS: TB has high incidence in SOTR even in low-prevalence
regions but especially targets patients who originated from TB-endemic countries.
Long-term TB-specific T cell responses were found in the majority of patients.
PMID- 29944617
TI - Maximizing Utilization in Pancreas Transplantation: Phenotypic Characteristics
Differentiating Aggressive From Nonaggressive Transplant Centers.
AB - BACKGROUND: Maximizing pancreas utilization requires a balance between judicious
donor selection and transplant center aggressiveness. We sought to determine how
such aggressiveness affects transplant outcomes. METHODS: Using the Scientific
Registry of Transplant Recipients, we studied 28 487 deceased-donor adult
pancreas transplants. Donor and recipient demographic factors indicative of
aggressiveness were used to score center aggressiveness. We compared outcomes of
low (> 1 SD below mean), medium (+/- 1 SD from mean), and high (> 1 SD above
mean) aggressiveness centers using bivariate and multivariable regressions.
RESULTS: Donor and recipient aggressiveness demonstrated a roughly linear
relationship (R = 0.20). Center volume correlated moderately with donor (rs =
0.433) and recipient (rs = 0.270) aggressiveness. In bivariate analysis, there
was little impact of donor selection aggressiveness on graft survival. Further,
for simultaneous pancreas and kidney transplants, centers with greater recipient
aggressiveness selection had better graft survival. High-volume centers had
better graft survival than low-volume centers. In multivariable analysis, donor
aggressiveness did not have an effect on graft survival, whereas graft survival
for medium (hazard ratio [HR], 0.66, 95% confidence interval [95% CI], 0.53-0.83)
and high (HR, 0.67; CI, 0.51-0.86) recipient aggressiveness performed better than
low-aggressiveness centers. There was a clear volume effect, with high-volume
centers (>20 transplants/year; HR, 0.69; CI, 0.61-0.79) performing better than
low-volume centers. CONCLUSIONS: Center practice patterns using higher-risk
donors and recipients did not negatively affect outcomes. This effect is likely
mediated through efficiencies gained with the increased transplant volumes at
these centers.
PMID- 29944618
TI - Preoperative autologous blood collection in adult living liver donors: Are we
wasting donor blood and increasing exposure to risk?
AB - BACKGROUND: Despite waning indications in the general population for preoperative
autologous blood donation (PABD), it is a procedure that continues to be offered
to healthy living liver donors (LLD). In this study we sought to understand the
impact of PABD on the LLD population. METHODS: We retrospectively reviewed charts
of one institution's LLDs over a 2-year period. Per institutional protocol, all
accepted LLD donated 1 unit of autologous blood prior to living donor hepatectomy
(LDH). RESULTS: Sixty-six LLDs underwent PABD and 59 of these donors underwent
LDH. In this cohort, there was a significant 1.2 g/dL drop in HB from baseline
(prior to PABD) to the evening before surgery. Mean (SD) procedure estimated
blood loss was 260 mL (+/-100), mean (SD) resected graft weight was 592 g (+/
174). No allogeneic blood was transfused. 42% of LLD received autologous
transfusion. Mean (SD) pretransfusion HB of transfused LLDs was 11.7 g/dL (+/-
1.2). All LLDs had negative antibody screens. 63% of donated autologous units
were discarded. CONCLUSIONS: PABD in our population is associated with decreased
preoperative HB, increased exposure of healthy LLD to unnecessary transfusion
related risks, and high rates of discarded blood product. We encourage further
investigation and reconsideration of the practice of PABD and autologous
transfusion in LLDs.
PMID- 29944619
TI - Efficacy of IgM-Enriched Immunoglobulin for Vasopressor-Resistant Vasoplegic
Shock After Liver Transplantation.
AB - BACKGROUND: Vasoplegia is a clinical condition typically manifested by
cardiovascular instability unresponsive to usual doses of inotropes or
vasopressors. It can occur in a variety of clinical settings including liver
transplantation (LT). Immunoglobulins have been used to treat sepsis-related
vasoplegia. We performed a retrospective study to evaluate the efficacy of IgM
enriched immunoglobulin (IgMIg) on 30-day mortality and its ability to reverse
vasoplegia in patients undergoing LT. METHODS: Between 5/2013 and 11/2017, 473 LT
were performed at our institution. We identified 21 patients who received IgMIg
for 3 days to treat vasoplegia. Patients included in the study met the criteria
for having vasoplegia and required noradrenaline administration greater than 1
MUg/kg/min for more than 24 h to maintain a mean arterial pressure (MAP) >= 70
mmHg. Procalcitonin (PCT) and interleukin-6 (IL-6) levels were used as surrogate
markers for inflammation and were measured at the beginning and end of IgM
treatment. RESULTS: After IgMIg administration, median noradrenaline infusion
rates could be significantly reduced from 1.6 (1.3-2) MUg/kg/min to 0.16 (0.08
0.34) MUg/kg/min (P < 0.001). In addition, after treatment, PCT levels decreased
significantly from 44 ng/ml (24-158) to 26.1 ng/ml (10.9-48.7) (P < 0.001) and IL
6 levels decreased significantly from 63 pg/ml (29-102) to 20 pg/ml (11-20) (P <
0.001). Thirty-day morality was 14.3%. CONCLUSIONS: The administration of IgMIg
in patients with vasoplegia after LT is associated with a return of hemodynamic
stability. Despite a predicted mortality of over 90% by SOFA score, the mortality
rate of patients receiving IgMIg in our study was less than 20%.
PMID- 29944620
TI - The Importance of Outcome Metrics in Allocation Policy.
PMID- 29944621
TI - Implementing Lean in Academic Primary Care.
AB - BACKGROUND: Lean is emerging as a quality improvement (QI) strategy in health
care, but there has been minimal adoption in primary care teaching practices.
This study describes a strategy for implementing Lean in an academic family
medicine center and provides a formative assessment of this approach. METHODS: A
case study of the University of North Carolina Family Medicine Center that used
the Consolidated Framework for Implementation Research to guide a formative
evaluation. The implementation strategy included partnering with Lean content
experts and creating a leadership team; planning and completing QI events and
Lean training modules; and evaluating and reporting activities related to QI and
training. RESULTS: During the initial period of Lean implementation, there was
(1) minimal to no change in the quality of care as determined by the Preventive
Care Index (46-48); (2) a decrease patient appointment cycle time from 89 minutes
to 65 minutes; (3) an increase in overall practice productivity from $8144 to
$9160; (4) a decrease in patient satisfaction from 94% to 91%; and (5) an
increase in monthly visit volume from 4112 to 5076. CONCLUSION: Lean had an
uneven effect on QI in an academic primary care practice during the first year of
implementation.
PMID- 29944622
TI - Physician Engagement With Metrics in Lean Primary Care Transformation.
AB - OBJECTIVE: Data and metrics play important roles in quality and process
improvement efforts. For one specific process improvement method, Lean or Lean
health care, data and metrics are central components, allowing users to identify
areas that need improvement and to assess the degree to which improvements have
been realized. This article explores the role that metrics and measurement played
in a wide-reaching "Lean"-based continuous quality improvement effort carried out
in the primary care departments of a large, ambulatory care health care
organization. METHODS: This article is based on qualitative data collected
through in-depth interviews with physicians, staff, and health care leaders.
RESULTS: Suggestions for improving the ways that metrics may be optimally used,
presented, and approached while carrying out health care improvement efforts
include having accurate and compelling data throughout the improvement process,
ensuring that metrics are professionally meaningful to physicians, and presenting
metrics in a manner that increases the likelihood that they will be digested and
ultimately used to improve health care. CONCLUSIONS: Effective strategies for
selecting and presenting metrics to practicing physicians are an important part
of a successful quality improvement effort.
PMID- 29944623
TI - Creating and Sustaining Care Teams in Primary Care: Perspectives From Innovative
Patient-Centered Medical Homes.
AB - OBJECTIVE: To learn from the experiences of innovative primary care practices
that have successfully developed care teams. RESEARCH DESIGN: A 21/2-day working
conference was convened with representatives from 10 innovative primary care
practices, content experts, and researchers to discuss experiences of developing
care teams. Qualitative data included observation notes, transcripts of
conference sessions and interviews, and narrative summaries of innovations. Case
summaries of practices and an analysis matrix were created to identify common
themes. PARTICIPANTS: Ten practices known nationally for innovations in team
based care participated in the conference represented by 1 to 2 practice members.
RESULTS: Two domains emerged related to creating effective teams and funding
them. Participants emphasized the importance of making practice values explicit
and involving everyone in the change process, standardizing routine processes,
and mitigating resistance. They also highlighted that team-based care adds
comprehensiveness, not necessarily productivity. They, thus, highlighted the need
for a long-term financial vision, including resourcefulness and alternate
funding. CONCLUSIONS: Team-based care is possible and valuable in primary care.
It is difficult to develop and sustain, however, and requires dedicated time and
resources. The challenges these highly motivated practices described raise the
question of feasibility for more average practices in the current funding
environment.
PMID- 29944624
TI - Implementing a Comprehensive Unit-Based Safety Program (CUSP) to Enhance a
Culture of Patient Safety and Improve Medication Safety in a Regional Home Care
Program.
AB - OBJECTIVE: To determine whether a Comprehensive Unit-based Safety Program could
be used to enhance a culture of patient safety and improve medication safety at 1
pilot site. METHODS: The Canadian Patient Safety Culture Survey tool was used to
assess the culture of patient safety and drill down on the key factors
contributing to medication errors. Based on staff input and site improvement team
investigations, solutions were developed to address medication safety issues. The
main outcome measure was pre-/postintervention Canadian Patient Safety Culture
scores. Change in frequency of occurrence reporting and staff's overall project
experience were also measured. RESULTS: Overall perceptions of patient safety
culture improved from 70% preintervention to 76.8% postintervention, representing
a 9.7% change. Volume of occurrence reporting showed a marked increase
postintervention. The project was well received by staff, with 84% rating their
experience as "Good" to "Excellent." Finally 100% of participants reported that
they learned something new and that this information could be applied to improve
their day-to-day work. CONCLUSION: Implementing a Comprehensive Unit-based Safety
Program improved staff's perceptions of patient safety, contributing to improved
medication safety. To our knowledge, this is the first application of
Comprehensive Unit-based Safety Program to successfully enhance patient safety in
the home care setting.
PMID- 29944625
TI - The Nature and Severity of Adverse Events in Select Outpatient Surgical
Procedures in the Veterans Health Administration.
AB - BACKGROUND: Research on adverse events (AEs) in outpatient surgery has been
limited. As part of a Veterans Health Administration (VA) project on AE
surveillance, we chart-reviewed selected outpatient surgical cases to
characterize the nature and severity of AEs. METHODS: We abstracted financial
year 2012-2015 VA outpatient surgery cases selected with high (n = 1185) and low
(n = 1072) likelihood of an AE based on postoperative health care utilization.
The abstraction tool included established AE definitions and validated harm and
severity scales. RESULTS: We found AEs in 608 high-likelihood (51%) and 126 low
likelihood outpatient surgical procedures (12%). Among 1010 unique AEs, the most
common were wound issues (n = 261, 26%), urinary retention (23%), and urinary
tract infections (12%). While 63% of all AEs involved minimal harm, 28% required
hospitalization, and 9% were severely harmful including 8 AEs requiring
intervention to sustain life and 2 deaths. Overall, 102 AEs (10%) required, at
minimum, a repeat surgery to treat. CONCLUSIONS: Among VA outpatient surgical
procedures selected based on likelihood of an AE, nearly 40% of identified events
carried more than minimal patient harm, undermining the claim that outpatient
surgery is relatively safe. Prevalent and preventable AEs such as wound
dehiscence and urinary retention may be useful targets for quality improvement.
PMID- 29944626
TI - Getting New Test Results to Patients.
AB - : : New diagnostic results are constantly arriving to outpatient practices. It is
imperative to effectively communicate these results and their implications to
patients. METHODS: We surveyed 100 patients and our clinic personnel to assess
opinions regarding methods of communication in common scenarios. RESULTS:
Response rate was 79% from patients and 75% from clinic personnel. Most patients
thought letters were an appropriate way to receive normal test results (83%).
They also felt medical-technician calls were appropriate for normal results
(88%), medication dose changes (75%), or need for additional studies (71%).
Respondents considered nurse calls acceptable in most scenarios except for new
diagnoses of cancer or need for surgery; the consensus was that physicians should
directly communicate to patients in these situations. CONCLUSIONS: Providers
should take the time to discuss results with patients that lead to significant
interventions, but employ support staff to disseminate information about normal
results, medication dose changes, and need for additional diagnostic testing.
PMID- 29944627
TI - Preventability of 28-Day Hospital Readmissions in General Internal Medicine
Patients: A Retrospective Analysis at a Quaternary Hospital.
AB - BACKGROUND: Unplanned hospital readmissions are associated with increased patient
mortality and health care costs, yet only a fraction are likely to be
preventable. This study's objective was to identify preventable hospital
readmissions of general internal medicine patients, and their common causes.
METHODS: Patients who were discharged from the general internal medicine teaching
service and readmitted to hospital within 28 days for 24 hours or more were
recruited to the study; they were identified via the hospital electronic medical
record system. Data were gathered via structured review of hospital
charts/electronic medical records, along with standardized patient interviews.
Unique to our study, a multidisciplinary panel of physicians, nurses, and
hospital administrators adjudicated preventability and identified common causes
of readmission. RESULTS: Fifty-five hospital readmissions were identified; 53%
were adjudicated to be preventable. There was no difference in any variable
analyzed between preventable and nonpreventable readmissions. The most common
causes of preventable readmissions were inadequate coordination of community
services upon discharge, insufficient clinical postdischarge follow-up, and
suboptimal end-of-life care. CONCLUSION: This study identified a higher
proportion of preventable 28-day hospital readmissions when compared with prior
research. Increased involvement of palliative care during initial hospitalization
for appropriate conditions and improvements in care after discharge may reduce
preventable hospital readmissions.
PMID- 29944628
TI - Quality Reporting by Payers: A Mixed-Methods Study of Provider Perspectives and
Practices.
AB - BACKGROUND: Providers need timely, clinically meaningful, and actionable
information to improve quality of care. Payers may play an important role in
providing such information in ambulatory care settings. We sought to learn about
providers' use and perceptions of quality reports from insurers. METHODS: We
employed a mixed-methods study design. We analyzed the performance of 118
provider groups on 21 HEDIS measures included in one New England insurer's
quality reporting program and evaluated how a subset of provider groups (n = 55)
accessed the reports. We also conducted 14 semistructured interviews with
providers and administrators to assess their perspectives about quality reports
from insurers in general. RESULTS: Performance on quality measures varied greatly
across provider groups and by metric. Only 20% of provider groups accessed the
quality reports during the study period. While providers reported that payer
information on quality has the potential to be useful, respondents suggested
important reasons why insurer quality reports were not widely accessed, including
information overload, conflicts with other sources of information, and the
significant provider effort required to make the reports actionable. CONCLUSIONS:
Payer-provider collaborations are needed to improve the usefulness of payers'
quality measurement reports, and coordination among payers is needed to
streamline reported measures.
PMID- 29944629
TI - Enhancing Financial Performance: An Application of Lean Six Sigma to Reduce
Insurance Claim Denials.
AB - Health systems typically lose approximately 3% to 5% of net revenues annually due
to insurance claim denials. While most denials can be appealed, the
administrative burden of sorting through and appealing them can be time consuming
and delays the revenue collection process. This article describes how the Lean
Six Sigma methodology was used to improve the revenue cycle by reducing insurance
claim denials for a leading pediatric hospital in the United States. The use of
this approach is demonstrated through a case example focused on reducing denials
by improving the hospital's Emergency Center registration process. Multiple pilot
tests were performed to ensure the proposed changes sufficiently addressed the
problem of missing/incomplete insurance information. Results indicated that the
revised registration form reduced missing/incomplete fields by 67%. As a result,
the revised form was implemented, which helped greatly reduce insurance claim
denials. In addition to providing an example from which other health systems can
learn to successfully implement Lean Six Sigma to enhance the performance of
their revenue cycle, this work helped the hospital in which this research was
performed improve its patient experience by making it easier for patients to
complete their Emergency Center registration form.
PMID- 29944631
TI - High-Value Care for Cataract Surgery: Questioning the Utility of Routine
Preoperative Medical Evaluation.
PMID- 29944630
TI - Identification of Children as Relatives With a Systematic Approach; a
Prerequisite in Order to Offer Advice and Support.
AB - The purpose of this study was to elucidate conditions at all system levels in a
specific health care service to develop practices for identification of children
as relatives. An interactive research approach with the intention to create
mutual learning between practice and research was used. The participating health
care service cared for both clinic in- and outpatients with psychiatric
disorders. Health care professionals from different system levels (micro, meso,
macro) participated, representing different professions. At the first project
meeting, it was obvious that there was no systematic approach to identify
children as relatives. At the micro level, activities such as a pilot survey and
an open house activity were carried out. At the meso level, it was discussed how
to better support collaboration between units. At the management (macro) level,
it was decided that all units should appoint at least one child agent, with the
aim to increase collaboration throughout the whole health care service. To change
focus, in this case from only parents to inclusion of children, is an important
challenge faced by health care services when forced to incorporate new policies
and regulations. The new regulations contribute to increased complexity in
already complex organizations. This study highlights that such challenges are
underestimated.
PMID- 29944632
TI - How Community-Based Health Systems Can Embrace Research in the Fee-for-Value Era.
PMID- 29944636
TI - The impact of genitourinary syndrome of menopause on well-being, functioning, and
quality of life in postmenopausal women.
AB - OBJECTIVE: Symptoms of genitourinary syndrome of menopause (GSM) are bothersome
to middle-aged and older women, and affect their quality of life (QoL),
sexuality, and daily activities. The objective of the study was to evaluate the
impact of vaginal symptoms and GSM on the well-being, functioning, and QoL of
postmenopausal women from Spain. METHODS: This study involved 423 postmenopausal
women participating in the GENISSE study (a multicenter, cross-sectional,
descriptive, observational study) who presented at least 1 vaginal symptom. All
women completed the "day-to-day impact of vaginal aging" (DIVA) questionnaire.
Analysis of total scores and subdomains of the questionnaire were performed in
women diagnosed with GSM and those without the condition. RESULTS: In these
women, the highest mean scores on the DIVA questionnaire were found in the sexual
functioning domain long version (mean 1.8; SD 1.0), followed by the sexual
functioning domain short version (mean 1.7; SD 1.1), self-perception and body
image (mean 1.4; SD 1.1), activities of daily living (mean 0.7; SD 0.8), and
emotional well-being (mean 0.7; SD 0.8) scales. A total of 299 women (70.7%) had
vaginal symptoms with a diagnosis of GSM, whereas 124 (29.3%) had no GSM
diagnosis. Scores on the DIVA questionnaire were significantly higher in women
with a diagnosis of GSM than in those without this condition. CONCLUSIONS:
Vaginal symptoms impact the well-being, functioning, and QoL of postmenopausal
women, especially sexual function, self-perception, and body image. This impact
is significantly higher in women with GSM. Identifying and treating patients
affected by vaginal symptoms and GSM may be beneficial for improving their QoL.
PMID- 29944637
TI - In Reply.
PMID- 29944638
TI - The naturally derived small compound Osthole inhibits osteoclastogenesis to
prevent ovariectomy-induced bone loss in mice.
AB - OBJECTIVE: This study was to determine the bone protective effects and underlying
mechanisms of Osthole (OT) in ovariectomized (OVX) mice. We found that the
inhibitory effects of OT on receptor activator of nuclear factor kappa-B ligand
(RANKL)-activated osteoclastogenesis are responsible for its bone protective
effects in OVX mice. METHODS: Eight-week-old mice were ovariectomized and OT (10
mg/kg/d) was intraperitoneally administrated to OVX mice 7 days after the surgery
and were sacrificed at the end of the 3 months. Osteoclasts were generated from
primary bone marrow macrophages (BMMs) to investigate the inhibitory effects of
OT. The activity of RANKL-activated signaling was simultaneously analyzed in
vitro and in vivo using immunohistochemistry, Western blot, and PCR assays.
RESULTS: OT dose dependently inhibited RANKL-mediated osteoclastogenesis in BMM
cultures. OT administration attenuated bone loss (mg Ha/cm: 894.68 +/- 33.56 vs
748.08 +/- 19.51, P < 0.05) in OVX mice. OT inhibits osteoclastogenesis (Oc.N/per
view area: 72 +/- 4.3 vs 0.8 +/- 0.4, P < 0.05) and bone resorption activity
(bone resorbed percentages %, 48.56 +/- 7.25 vs 3.25 +/- 1.37, P < 0.05) from
BMMs. Mechanistically, OT inhibited the expressions of nuclear factor of
activated T-cells c1 (NFATc1) and c-Fos. Moreover, OT suppressed the expression
of RANKL-induced osteoclast marker genes, including matrix metalloproteinase 9
(MMP9), Cathepsin K (Ctsk), tartrate-resistant acid phosphatase (TRAP), and
carbonic anhydrase II (Car2). CONCLUSIONS: OT inhibits RANKL-mediated
osteoclastogenesis and prevents bone loss in OVX mice. Our findings revealed that
OT is a potential new drug for treating postmenopausal osteoporosis.
PMID- 29944639
TI - To the Editor.
PMID- 29944641
TI - Condom Use, Multiple Rounds of Sex, and Alcohol Use Among South African Women Who
Use Alcohol and Other Drugs: An Event-Level Analysis.
AB - BACKGROUND: High rates of alcohol and other drug use contribute to the ongoing
generalized human immunodeficiency virus epidemic in South Africa. Despite the
general link between alcohol use and condomless sex, findings from event-level
studies of the relationship between alcohol use and condomless sex during the
same encounter have been inconsistent. METHODS: We conducted event-level analyses
of the most recent sexual encounter reported by 636 women who use substances in
Pretoria. Data were collected via a questionnaire that included questions about
the number of rounds of vaginal and anal sex and condom use during each round. We
used multiple logistic regression analyses to model the associations between
alcohol use by both partners and having multiple rounds of sex, and alcohol use
and condom use during all rounds of sex. RESULTS: Over 50% of encounters involved
multiple rounds of vaginal or anal sex. Encounters that involved multiple rounds
of sex were associated with inconsistent condom use. Encounters in which both
partners drank alcohol were more likely to involve condomless sex, as compared
with encounters in which one or neither partner drank alcohol. CONCLUSIONS: These
findings raise the possibility that prior event-level studies, which do not ask
about multiple rounds of sex, may underestimate the prevalence of condomless sex.
The association between alcohol use by both partners and condomless sex may
partially explain inconsistent associations between alcohol use and condom use in
event-level studies that did not assess the number of partners drinking.
PMID- 29944642
TI - Impact of Providing Preexposure Prophylaxis for Human Immunodeficiency Virus at
Clinics for Sexually Transmitted Infections in Baltimore City: An Agent-based
Model.
AB - BACKGROUND: Preexposure prophylaxis (PrEP) greatly reduces the risk of human
immunodeficiency virus (HIV) acquisition, but its optimal delivery strategy
remains uncertain. Clinics for sexually transmitted infections (STIs) can provide
an efficient venue for PrEP delivery. METHODS: To quantify the added value of STI
clinic-based PrEP delivery, we used an agent-based simulation of HIV transmission
among men who have sex with men (MSM). We simulated the impact of PrEP delivery
through STI clinics compared with PrEP delivery in other community-based
settings. Our primary outcome was the projected 20-year reduction in HIV
incidence among MSM. RESULTS: Assuming PrEP uptake and adherence of 60% each,
evaluating STI clinic attendees and delivering PrEP to eligible MSM reduced HIV
incidence by 16% [95% uncertainty range, 14%-18%] over 20 years, an impact that
was 1.8 (1.7-2.0) times as great as that achieved by evaluating an equal number
of MSM recruited from the community. Comparing strategies where an equal number
of MSM received PrEP in each strategy (ie, evaluating more individuals for PrEP
in the community-based strategy, because MSM attending STI clinics are more
likely to be PrEP eligible), the reduction in HIV incidence under the STI clinic
based strategy was 1.3 (1.3-1.4) times as great as that of community-based
delivery. CONCLUSIONS: Delivering PrEP to MSM who attend STI clinics can improve
efficiency and effectiveness. If high levels of adherence can be achieved in this
population, STI clinics may be an important venue for PrEP implementation.
PMID- 29944643
TI - Challenges of Rapid Plasma Reagin Interpretation in Syphilis Screening in Uganda:
Variability in Nontreponemal Results Between Different Laboratories.
AB - BACKGROUND: Syphilis is a cause of morbidity and mortality and is of particular
concern in pregnancy in low-income countries because of the risks associated with
maternal-fetal transmission. Ugandan national guidelines recommend a
nontreponemal rapid plasma reagin (RPR) followed by treponemal testing for
diagnosis of syphilis. The RPR test confirms a reactive specific treponemal test,
or confirms serological "cure" with a 4-fold dilutional decrease; RPR is beset
with technical and biological limitations, making accurate diagnosis and
appropriate treatment problematic. The aim of this analysis was to compare
performance of RPR testing in different laboratories. METHODS: Stored, freeze
thawed sera from 215 participants were additionally tested for RPR and dilutional
titer in 2 different reference laboratories. Discrepant results were tested at a
third reference laboratory which served as a tie-breaker. Equivalence in RPR
titer was defined as within 2-fold or less. All patients with reactive rapid
tests were treated as per Ugandan National Guidelines. RESULTS: Of 215 sera, 97
(45.1%) were RPR reactive in clinic laboratory A, 81 (37.7%) and 65 (30.2%) were
RPR reactive in laboratories B and C, respectively. All reported positive in
laboratory C were positive in laboratory B. Discrepant results were tested in
laboratory D. chi Test was highly significant (P = <0.001) for difference between
each dyad of laboratories (A and B, A and C, and B and C) RPR results. There were
significant differences between RPR titers by paired t test and Wilcox rank test
(P = <0.001); with up to a 3-fold difference between laboratories. Two one-sided
test approach demonstrated nonequivalence. Agreement between laboratories B-D,
and C-D: 48 (98.0%) of 49 and 34 (69.4%) of 49, respectively (P = <0.001).
Laboratories B and D showed no significant difference and had equivalent RPR
titers. Laboratories C and D had different titers (P = <0.001) and were not
equivalent. CONCLUSIONS: We found significant interlaboratory discrepant RPR
results. A 3-fold difference in results is likely to be clinically significant
and could result in undertreatment or overtreatment. These data demonstrate a key
limitation of the RPR test and underline the urgent need for a more reproducible
quantitative test than the current RPR for diagnosing and determining cure of
syphilis.
PMID- 29944644
TI - A Comparison of Syphilis Partner Notification Outcomes by Reported Use of
Internet-based Apps to Meet Sex Partners in North Carolina, 2013-2016.
AB - BACKGROUND: Partner notification services (PNS) remain the backbone of syphilis
control. The popularity of Internet-based apps to meet sex partners among early
syphilis (ES) patients may hinder the success of PNS if partners cannot be
located. METHODS: We compared demographic and clinical characteristics between
male ES patients indicating sex with men (MSM) and reported in North Carolina
between 2013 and 2016 by reported use of an Internet-based app to meet sex
partners (app user). We used multivariable log-binomial regression to assess the
association between app usage and ES exposure notification of 1 or more sex
partner. RESULTS: Among 3414 MSM ES patients, 58.6% were app users. App users
were more frequently white (33.2% vs 27.3%; P = 0.003), younger (median, 28 years
vs 30 years; P = 0.0002) and less frequently human immunodeficiency virus
coinfected (54.1% vs 58.2%; P = 0.02) compared to non-app users. Overall, 94.9%
of app users and 89.6% of non-app users reported 1 or more sex partner. App users
reported 2.5 times more locatable and 2.7 times more unlocatable sex partners
than non-app users. Similar proportions of app (23.6%) and non-app users (25.0%)
reported only unlocatable partners (P = 0.4). App usage was not associated with
ES exposure notification of 1 or more sex partner (adjusted risk ratio, 0.99; 95%
confidence interval, 0.87-1.13). CONCLUSIONS: We observed no difference in the
proportion of locatable partners or likelihood of notifying 1 or more sex partner
of exposure among MSM ES patients, by reported use of Internet-based apps to meet
sex partners. Partner notification services continues to be an important
mechanism to locate and assure treatment for sex partners in this population.
PMID- 29944645
TI - Disclosure of Sexual Behavior Is Significantly Associated With Receiving a Panel
of Health Care Services Recommended for Men Who Have Sex With Men.
AB - BACKGROUND: Men who have sex with men (MSM) are at high risk for sexually
transmitted infections (STIs). National guidelines recommend that MSM receive
HIV, syphilis, gonorrhea, and chlamydia screening at least annually, and
hepatitis A and B and human papillomavirus vaccinations. We investigated
associations between disclosure of male-male sexual orientation/behavior and
receipt of this panel of services. METHODS: Gay, bisexual, and other MSM aged 18
through 26 years were enrolled from health clinics serving lesbian, gay,
bisexual, and transgender communities in Los Angeles and Chicago during 2012 to
2014. Participants completed a computer-assisted self-interview regarding health
care services, disclosure of sexual orientation/behavior, and recent HIV test
results. Proportions receiving recommended care, prevalence ratios (PRs), and 95%
confidence intervals (CIs) were calculated using SAS 9.4. RESULTS: Overall, 817
participants visited a provider within the past year. Of these, 525 (64.3%) had
disclosed, and 749 (91.7%) felt they could disclose if important to health. In
total, 548 (67.1%) received all STI screenings, and 74 (9.1%) received all
vaccinations. Only 105 (12.9%) received any human papillomavirus vaccination.
More disclosing participants received all recommended screenings (adjusted PR
[aPR],1.4; 95% CI, 1.3-1.6) and all recommended care components (aPR, 2.2; 95%
CI, 1.4-4.3) than nondisclosing participants. CONCLUSIONS: Despite national
recommendations, receipt of a complete panel of STI care services was low among
young MSM. Vaccine uptake was lower than STI screening. However, most
participants visited a health care provider in the past year and most disclosed,
suggesting opportunities to improve services. Providers might encourage
disclosure by improving sexual history taking and education, which could increase
opportunities for MSM to receive recommended care.
PMID- 29944649
TI - Antibiotic prophylaxis-Preventing severe infections and saving lives in poor
countries with very high mortality risk.
AB - In a Perspective, Keith P. Klugman and Rasa Izadnegahdar from the Bill and
Melinda Gates Foundation discuss the potentials and risks of antibiotic
prophylaxis interventions for infectious disease outbreaks in rural regions, such
as sub-Saharan Africa with very high mortality rates, when primary prophylactic
vaccination programs are not yet available.
PMID- 29944647
TI - Toll-Like Receptor 4 (TLR4) Stimulates Synovial Injury of Temporomandibular Joint
in Rats Through the Activation of p38 Mitogen-Activated Protein Kinase (MAPK)
Signaling Pathway.
AB - BACKGROUND Synovitis is an important disease that cause intractable pain in
temporomandibular joint (TMJ), and the inflammation process played a crucial role
in the initiation and development of temporomandibular joint disorder. A series
of investigations suggested that the increasing expression of interleukin-(IL)
1beta secreted by synovial lining cells plays an important role in synovial
inflammation and cartilage destruction in TMJ. In this present study, we
investigated the signaling pathways which regulate the expression of IL-1beta.
MATERIAL AND METHODS The occlusal interference animal model was created to induce
synovial injury. Forty-eight rats were divided into 4 groups: 1) control group,
2) occlusal interference group, 3) TAK-242 (a specific inhibitor targeting the
Toll-like receptor (TLR)-4) group, and 4) SB203580 (a specific inhibitor
targeting the p38) group. The inflammation changes were observed, and the
expression of p38 and IL-1beta in the synovial membranes were assayed. RESULTS
The results showed that downstream p38 MAPK (mitogen-activated protein kinase)
signaling was triggered following the activation of TLR4. Moreover, the injection
of SB203580 could inhibit the inflammatory reactions and the increased expression
of IL-1beta at both mRNA and protein levels. CONCLUSIONS The results prompted us
that TLR4 may stimulates synovial inflammatory reactions and increased expression
of IL-1beta in rats through the activation of p38 MAPK signaling pathway, p38 was
an important mediator in the mechanisms of the initiation and development of
synovial injury by regulating the expression of IL-1beta in synovial membranes.
PMID- 29944646
TI - Prevalence and Correlates of Point-of-sex Human Immunodeficiency Virus Self
testing Among Human Immunodeficiency Virus-negative Men Who Have Sex With Men in
China.
AB - BACKGROUND: Human immunodeficiency virus (HIV) self-testing (HIVST) provides a
promising tool to screen sex partners for men who have sex with men (MSM) who
engage in condomless sex and want to avoid HIV infection. Although previous
studies have demonstrated HIVST acceptability and increased testing uptake,
limited data exist on its use between sex partners for point-of-sex HIV testing.
This study examined prevalence and correlates of point-of-sex HIVST among Chinese
MSM. METHODS: A cross-sectional survey was conducted among 400 HIV-negative
Chinese MSM in 2017. Participants were recruited through a multifaceted sampling
approach and self-administered an electronic questionnaire. Point-of-sex HIVST
was measured by asking participants if they had ever conducted HIVST with a sex
partner before sex to ensure that they both knew their HIV statuses.
Multivariable logistic regression was used to identify correlates of point-of-sex
HIVST after controlling for age, education and sexual orientation. RESULTS:
Overall, 19.2% (77/400) men reported point-of-sex HIVST (51.3% among self
testers). Participants who had four or more HIV self-tests before had 7.57-fold
greater odds (95% confidence interval, 3.75, 15.28) of reporting point-of-sex
HIVST compared to those who had fewer HIVST experiences. Point-of-sex HIVST was
otherwise not associated with most other socio-demographic or behavioral
practices, suggesting that it may be broadly acceptable. CONCLUSIONS: A
substantial proportion of Chinese MSM had utilized HIVST with their partners
before sex, especially among those who were more experienced with HIVST. Scale up
and routine implementation of HIVST programs are further warranted to facilitate
point-of-sex HIV testing.
PMID- 29944651
TI - Single-dose oral ciprofloxacin prophylaxis as a response to a meningococcal
meningitis epidemic in the African meningitis belt: A 3-arm, open-label, cluster
randomized trial.
AB - BACKGROUND: Antibiotic prophylaxis for contacts of meningitis cases is not
recommended during outbreaks in the African meningitis belt. We assessed the
effectiveness of single-dose oral ciprofloxacin administered to household
contacts and in village-wide distributions on the overall attack rate (AR) in an
outbreak of meningococcal meningitis. METHODS AND FINDINGS: In this 3-arm, open
label, cluster-randomized trial during a meningococcal meningitis outbreak in
Madarounfa District, Niger, villages notifying a suspected case were randomly
assigned (1:1:1) to standard care (the control arm), single-dose oral
ciprofloxacin for household contacts within 24 hours of case notification, or
village-wide distribution of ciprofloxacin within 72 hours of first case
notification. The primary outcome was the overall AR of suspected meningitis
after inclusion. A random sample of 20 participating villages was enrolled to
document any changes in fecal carriage prevalence of ciprofloxacin-resistant and
extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae before and
after the intervention. Between April 22 and May 18, 2017, 49 villages were
included: 17 to the control arm, 17 to household prophylaxis, and 15 to village
wide prophylaxis. A total of 248 cases were notified in the study after the index
cases. The AR was 451 per 100,000 persons in the control arm, 386 per 100,000
persons in the household prophylaxis arm (t test versus control p = 0.68), and
190 per 100,000 persons in the village-wide prophylaxis arm (t test versus
control p = 0.032). The adjusted AR ratio between the household prophylaxis arm
and the control arm was 0.94 (95% CI 0.52-1.73, p = 0.85), and the adjusted AR
ratio between the village-wide prophylaxis arm and the control arm was 0.40 (95%
CI 0.19-0.87, p = 0.022). No adverse events were notified. Baseline carriage
prevalence of ciprofloxacin-resistant Enterobacteriaceae was 95% and of ESBL
producing Enterobacteriaceae was >90%, and did not change post-intervention. One
limitation of the study was the small number of cerebrospinal fluid samples sent
for confirmatory testing. CONCLUSIONS: Village-wide distribution of single-dose
oral ciprofloxacin within 72 hours of case notification reduced overall
meningitis AR. Distributions of ciprofloxacin could be an effective tool in
future meningitis outbreak responses, but further studies investigating length of
protection, effectiveness in urban settings, and potential impact on
antimicrobial resistance patterns should be carried out. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02724046.
PMID- 29944653
TI - Accuracy of a "Single Question Nocturia Score" compared to the "International
Prostate Symptoms Score" in the evaluation of lower urinary tract symptoms in
benign prostatic hyperplasia: A study performed at Ndola Teaching Hospital,
Ndola, Zambia.
AB - INTRODUCTION: The International Prostate Symptom Score (IPSS) is a useful tool
approved by the World Health Organisation and the American Urological Association
to measure the severity of lower urinary tract symptoms (LUTS). Although commonly
used in urological practice, the IPSS has faced many challenges in terms of its
usage in developing countries. In our setting, most patients presenting with this
condition are elderly patients with a low literacy level. Given this background,
the IPSS could be time consuming and difficult to administer to such patients and
it may lead to additional costs to the services. OBJECTIVES: The objective of
this study was to compare the accuracy of a Single Question Nocturia Score (SQNS)
with the IPSS in evaluation of lower urinary tracts symptoms in men with Benign
prostatic hyperplasia(BPH). METHODS: The study was designed as a cross-sectional
study using researcher-administered IPSS and SQNS questionnaires. The
sensitivity, specificity, and correlation coefficient were used to compare the
results obtained. Sensitivity was defined as the ability of the SQNS to detect
severe-to-moderate symptoms, whereas specificity was defined as the ability of
the SQNS to detect mild-to-no symptoms. RESULTS: We recruited 162 patients with
an age range between 50 and 88 years. The mean age was 66.7 (standard deviation
+/- 8.97 years). The IPSS showed that 85 patients (52%) presented with mild
symptoms, and 77 patients (48%) presented with severe-to-moderate symptoms. In
contrast, the SQNS showed that 88 patients (54.3%) presented with mild symptoms
and 74 patients (46.7%) presented with severe-to-moderate symptoms. The
sensitivity of the SQNS was 91%, and the specificity was 87%. The correlation
coefficient of the SQNS to IPSS using Pearson correlation coefficient, was 0.74.
This study showed that in our setting, the SQNS may be used as an alternative to
the IPSS in assessing the severity of LUTS in men with BPH especially in a busy
clinic.
PMID- 29944652
TI - Trade challenges at the World Trade Organization to national noncommunicable
disease prevention policies: A thematic document analysis of trade and health
policy space.
AB - BACKGROUND: It has long been contested that trade rules and agreements are used
to dispute regulations aimed at preventing noncommunicable diseases (NCDs). Yet
most analyses of trade rules and agreements focus on trade disputes, potentially
overlooking how a challenge to a regulation's consistency with trade rules may
lead to 'policy or regulatory chill' effects whereby countries delay, alter, or
repeal regulations in order to avoid the costs of a dispute. Systematic empirical
analysis of this pathway to impact was previously prevented by a dearth of
systematically coded data. METHODS AND FINDINGS: Here, we analyse a newly created
dataset of trade challenges about food, beverage, and tobacco regulations among
122 World Trade Organization (WTO) members from January 1, 1995 to December 31,
2016. We thematically describe the scope and frequency of trade challenges,
analyse economic asymmetries between countries raising and defending them, and
summarise 4 cases of their possible influence. Between 1995 and 2016, 93 food,
beverage, and tobacco regulations were challenged at the WTO. 'Unnecessary' trade
costs were the focus of 16.4% of the challenges. Only one (1.1%) challenge
remained unresolved and escalated to a trade dispute. Thirty-nine (41.9%)
challenges focussed on labelling regulations, and 18 (19.4%) focussed on quality
standards and restrictions on certain products like processed meats and cigarette
flavourings. High-income countries raised 77.4% (n = 72) of all challenges raised
against low- and lower-middle-income countries. We further identified 4 cases in
Indonesia, Chile, Colombia, and Saudi Arabia in which challenges were associated
with changes to food and beverage regulations. Data limitations precluded a
comprehensive evaluation of policy impact and challenge validity. CONCLUSIONS:
Policy makers appear to face significant pressure to design food, beverage, and
tobacco regulations that other countries will deem consistent with trade rules.
Trade-related influence on public health policy is likely to be understated by
analyses limited to formal trade disputes.
PMID- 29944648
TI - Age density patterns in patients medical conditions: A clustering approach.
AB - This paper presents a data analysis framework to uncover relationships between
health conditions, age and sex for a large population of patients. We study a
massive heterogeneous sample of 1.7 million patients in Brazil, containing 47
million of health records with detailed medical conditions for visits to medical
facilities for a period of 17 months. The findings suggest that medical
conditions can be grouped into clusters that share very distinctive densities in
the ages of the patients. For each cluster, we further present the ICD-10
chapters within it. Finally, we relate the findings to comorbidity networks,
uncovering the relation of the discovered clusters of age densities to
comorbidity networks literature.
PMID- 29944654
TI - Correction: A Mixture of Delta-Rules Approximation to Bayesian Inference in
Change-Point Problems.
AB - [This corrects the article DOI: 10.1371/journal.pcbi.1003150.].
PMID- 29944650
TI - Cell-nonautonomous local and systemic responses to cell arrest enable long-bone
catch-up growth in developing mice.
AB - Catch-up growth after insults to growing organs is paramount to achieving robust
body proportions. In fly larvae, injury to individual tissues is followed by
local and systemic compensatory mechanisms that allow the damaged tissue to
regain normal proportions with other tissues. In vertebrates, local catch-up
growth has been described after transient reduction of bone growth, but the
underlying cellular responses are controversial. We developed an approach to
study catch-up growth in foetal mice in which mosaic expression of the cell cycle
suppressor p21 is induced in the cartilage cells (chondrocytes) that drive long
bone elongation. By specifically targeting p21 expression to left hindlimb
chondrocytes, the right limb serves as an internal control. Unexpectedly, left
right limb symmetry remained normal, revealing deployment of compensatory
mechanisms. Above a certain threshold of insult, an orchestrated response was
triggered involving local enhancement of bone growth and systemic growth
reduction that ensured that body proportions were maintained. The local response
entailed hyperproliferation of spared left limb chondrocytes that was associated
with reduced chondrocyte density. The systemic effect involved impaired placental
function and IGF signalling, revealing bone-placenta communication. Therefore,
vertebrates, like invertebrates, can mount coordinated local and systemic
responses to developmental insults that ensure that normal body proportions are
maintained.
PMID- 29944656
TI - Smombie Guardian: We watch for potential obstacles while you are walking and
conducting smartphone activities.
AB - With the growing dependence on smartphones for everyday activities, a large
number of pedestrians nowadays are constantly fixated on their smartphone
screens, and hence are susceptible to walking off pavements or colliding with
other pedestrians. Reduced attention and situational awareness can render
smartphone-occupied users, or smombies, oblivious to potential risks when using
their smartphones while walking or driving. In this paper, we introduce a
smartphone application, called Smombie Guardian, that detects obstacles and
alerts smombies as they walk while viewing their smartphone screens to prevent
potential collisions. Based on a user study with 74 participants who used Smombie
Guardian in a real-life scenario, we highlight the effectiveness, usefulness, and
unobtrusiveness of the algorithm and Smombie Guardian in helping users to avoid
potential obstacles.
PMID- 29944655
TI - Comparing post-acute rehabilitation use, length of stay, and outcomes experienced
by Medicare fee-for-service and Medicare Advantage beneficiaries with hip
fracture in the United States: A secondary analysis of administrative data.
AB - BACKGROUND: Medicare Advantage (MA) and Medicare fee-for-service (FFS) plans have
different financial incentives. Medicare pays predetermined rates per beneficiary
to MA plans for providing care throughout the year, while providers serving FFS
patients are reimbursed per utilization event. It is unknown how these incentives
affect post-acute care in skilled nursing facilities (SNFs). The objective of
this study was to examine differences in rehabilitation service use, length of
stay, and outcomes for patients following hip fracture between FFS and MA
enrollees. METHODS AND FINDINGS: This was a retrospective cohort study to examine
differences in health service utilization and outcomes between FFS and MA
patients in SNFs following hip fracture hospitalization during the period January
1, 2011, to June 30, 2015, and followed up until December 31, 2015. We linked the
Master Beneficiary Summary File, Medicare Provider and Analysis Review data,
Healthcare Effectiveness Data and Information Set data, the Minimum Data Set, and
the American Community Survey. The 6 primary outcomes of interest in this study
included 2 process measures and 4 patient-centered outcomes. Process measures
included length of stay in the SNF and average rehabilitation therapy minutes
(physical and occupational therapy) received per day. Patient-centered outcomes
included 30-day hospital readmission, changes in functional status as measured by
the 28-point late loss MDS-ADL scale, likelihood of becoming a long-term
resident, and successful discharge to the community. Successful discharge from a
SNF was defined as being discharged to the community within 100 days of SNF
admission and remaining alive in the community without being institutionalized in
any acute or post-acute setting for at least 30 days. We analyzed 211,296 FFS and
75,554 MA patients with hip fracture admitted directly to a SNF following an
index hospitalization who had not been in a nursing facility or hospital in the
preceding year. We used inverse probability of treatment weighting (IPTW) and
nursing facility fixed effects regression models to compare treatments and
outcomes between MA and FFS patients. MA patients were younger and less
cognitively impaired upon SNF admission than FFS patients. After applying IPTW,
demographic and clinical characteristics of MA patients were comparable with
those of FFS patients. After adjusting for risk factors using IPTW-weighted fixed
effects regression models, MA patients spent 5.1 (95% CI -5.4 to -4.8) fewer days
in the SNF and received 463 (95% CI to -483.2 to -442.4) fewer minutes of total
rehabilitation therapy during the first 40 days following SNF admission, i.e.,
12.1 (95% CI -12.7 to -11.4) fewer minutes of rehabilitation therapy per day
compared to FFS patients. In addition, MA patients had a 1.2 percentage point
(95% CI -1.5 to -1.1) lower 30-day readmission rate, 0.6 percentage point (95% CI
-0.8 to -0.3) lower rate of becoming a long-stay resident, and a 3.2 percentage
point (95% CI 2.7 to 3.7) higher rate of successful discharge to the community
compared to FFS patients. The major limitation of this study was that we only
adjusted for observed differences to address selection bias between FFS and MA
patients with hip fracture. Therefore, results may not be generalizable to other
conditions requiring extensive rehabilitation. CONCLUSIONS: Compared to FFS
patients, MA patients had a shorter course of rehabilitation but were more likely
to be discharged to the community successfully and were less likely to experience
a 30-day hospital readmission. Longer lengths of stay may not translate into
better outcomes in the case of hip fracture patients in SNFs.
PMID- 29944660
TI - Correction: Prevalence of sexually transmitted infections and bacterial vaginosis
among women in sub-Saharan Africa: An individual participant data meta-analysis
of 18 HIV prevention studies.
AB - [This corrects the article DOI: 10.1371/journal.pmed.1002511.].
PMID- 29944661
TI - Research on the sliding friction associated spur-face gear meshing efficiency
based on the loaded tooth contact analysis.
AB - In order to solve the problem of Meshing Efficiency of spur-face gear sliding
friction, a method for calculating the Meshing Efficiency of Spur-Face gear is
proposed based on Elastohydrodynamic lubrication (EHL) theory. Through the Tooth
Contact Analysis (TCA) and Loaded Tooth Contact Analysis technique (LTCA) method,
the meshing process of the Spur-Face gear was simulated. The calculation model of
Sliding friction coefficient was established by using non Newtonian quasi steady
thermal Elastohydrodynamic lubrication (TEHL) theory, and the calculation model
of Meshing Efficiency of Spur-Face gear was established. The influence of input
torque and rotational speed on Meshing Efficiency is analyzed. The results show
that Sliding friction coefficient is an important factor affecting the Meshing
Efficiency of gears. Sliding friction coefficient is not the same at different
positions of the tooth surface. Sliding friction coefficient is affected by input
speed and input torque. This method provides a theoretical basis for further
optimization calculation of Spur-Face gear.
PMID- 29944658
TI - Time to sputum smear and culture conversions in multidrug resistant tuberculosis
at University of Gondar Hospital, Northwest Ethiopia.
AB - BACKGROUND: Sputum smear and culture conversions are an important indicator of
treatment efficacy and help to determine treatment duration in multidrug
resistant tuberculosis (MDR-TB) patients. There are no published studies of
sputum smear and culture conversion of MDR-TB patients in Ethiopia. The objective
of this study is to evaluate and compare time to initial sputum smear and culture
conversion and to identify factors influencing time to culture conversion.
METHODS: A retrospective cohort study was conducted among all culture positive
and rifampicin mono resistant (RR) or MDR-TB patients from September 2011 to
August 2016 at University of Gondar Hospital. Sputum cultures were collected
monthly and conversion was defined as two consecutive negative cultures taken at
least 30 days apart. Data were entered using EpiData and exported to SPSS
software for analysis. Cox proportional hazard model was used to determine the
predictor variables for culture conversion. RESULTS: Overall, 85.5% (201/235) of
the patients converted their cultures in a median of 72 days (inter-quartile
range: 44-123). More than half (61.7%) of patients achieved culture conversion
within three months. The median time for sputum smear conversion was 54 days
(inter-quartile range: 31-72). The median time to culture conversion among HIV
positive patients was significantly shorter at 67 days (95% CI, 55.4-78.6)
compared to HIV negative patients, 77 days (95% CI, 63.9-90, p = 0.005).
Independent predictors of significantly longer time to sputum culture conversion
were underweight (aHR = 0.71, 95% CI, 0.52-0.97), HIV negative (aHR = 0.66, 95%
CI, 0.47-0.94) and treatment regimen composition (aHR = 0.57, 95% CI, 0.37-0.88).
Significantly higher rate of culture conversion was observed in 2015 (aHR = 1.86,
95% CI, 1.1-3.14) and in 2016 (aHR = 3.7, 95% CI, 1.88-7.35) years of treatment
compared to 2011. CONCLUSIONS: Majority of patients achieved sputum culture
conversion within three months and smear conversion within two months. Patients
with identified risk factors were associated with delayed culture conversion.
These factors should be considered during management of MDR-TB patients.
PMID- 29944663
TI - Development and evaluation of a mobile-optimized daily self-rating depression
screening app: A preliminary study.
AB - The aims of this study were to design a mobile app that would record daily self
reported Korean version of the Center for Epidemiologic Studies Depression Scale
Revised (K-CESD-R) ratings in a "Yes" or "No" format, develop two different
algorithms for converting mobile K-CESD-R scores in a binary format into scores
in a 5-point response format, and determine which algorithm would be more
appropriately applied to the newly developed app. Algorithm (A) was designed to
improve the scoring system of the 2-week delayed retrospective recall-based
original K-CESD-R scale, and algorithm (B) was designed to further refine the
scoring of the 24-hour delayed prospective recall-based mobile K-CESD-R scale
applied with algorithm (A). To calculate total mobile K-CESD-R scores, each
algorithm applied certain cut-off criteria for a 5-point scale with different
inter-point intervals, defined by the ratio of the total number of times that
users responded "Yes" to each item to the number of days that users reported
daily depressive symptom ratings during the 2-week study period. Twenty
participants were asked to complete a K-CESD-R Mobile assessment daily for 2
weeks and an original K-CESD-R assessment delivered to their e-mail accounts at
the end of the 2-week study period. There was a significant difference between
original and mobile algorithm (B) scores but not between original and mobile
algorithm (A) scores. Of the 20 participants, 4 scored at or above the cut-off
criterion (>=13) on either the original K-CESD-R (n = 4) or the mobile K-CESD-R
converted with algorithm (A) (n = 3) or algorithm (B) (n = 1). However, all
participants were assessed as being below threshold for a diagnosis of a mental
disorder during a clinician-administered diagnostic interview. Therefore, the K
CESD-R Mobile app using algorithm (B) could be a more potential candidate for a
depression screening tool than the K-CESD-R Mobile app using algorithm (A).
PMID- 29944657
TI - Genome analysis of the yeast Diutina catenulata, a member of the
Debaryomycetaceae/Metschnikowiaceae (CTG-Ser) clade.
AB - Diutina catenulata (Candida catenulata) is an ascomycetous yeast that has been
isolated from humans, animals and environmental sources. The species is a
contaminant of dairy products, and has been linked to superficial and invasive
infections in both humans and animals. Previous phylogenetic analyses have
assigned the species to the Saccharomycetales, but failed to identify its
specific clade. Here, we report the genome sequence of an environmental isolate
of D. catenulata. Examination of the tRNA repertoire and coding potential of this
species shows that it translates the CUG codon as serine and not leucine. In
addition, two phylogenetic analyses using 204 ubiquitous gene family alignments
and 3,826 single-copy genes both confirm the placement of the species in the
Debaryomycetaceae/Metschnikowiaceae, or CTG-Ser clade. The sequenced isolate
contains an MTLalpha idiomorph. However, unlike most MTL loci in related species,
poly (A) polymerase (PAP) is not adjacent to MTLalpha1.
PMID- 29944659
TI - Lessons learned and insights from the implementation of a food and physical
activity policy to prevent obesity in Mexican schools: An analysis of nationally
representative survey results.
AB - Obesity is a serious problem among children in Mexico. In 2010, the government
implemented a national food and physical activity policy in elementary schools,
to prevent obesity. The goal of this study is to assess the implementation of
this policy, using the logic model from a descriptive survey with national
representativeness at the elementary school level and based on a stratified
cluster design. We used a systematic random sampling of schools (n = 122),
stratified into public and private. We administered questionnaires to 116
principals, 165 members of the Food and Physical Activity Committees, 132 food
school food vendors, 119 teachers, 348 parents. This study evidences a
significant deviation in implementation from what had been planned. Our lessons
learned are the importance to: base the design/implementation of the policy on a
theoretical framework, make programs appealing to stakeholders, select concrete
and measurable objective or goals, and support stakeholders during the
implementation process.
PMID- 29944667
TI - Effect of different planting areas on the chemical compositions and hypoglycemic
and antioxidant activities of mulberry leaf extracts in Southern China.
AB - Guangdong, Guangxi and Chongqing are emerging sericulture areas in China where
the production of mulberry leaves is huge. In order to identity high quality
mulberry leaves that are suitable for healthy products to expand planting, 24
samples from three regions (Guangdong, Guangxi, Chongqing) in the south of China
were quantified for two alkaloids (1-deoxynojirimycin and fagomine) and five
phenols (chlorogenic acid, rutin, isoquercitrin, etc.) using high-performance
liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Additionally, the
total phenolic and total flavonoid contents, antioxidant and glycosidase
inhibitory activities (hypoglycemic activity) were tested using different assays
(DPPH, ABTS, FRAP) to comprehensively evaluate the quality of the mulberry
leaves. The contents of DNJ and fagomine ranged from 0.401+/-0.003 to 5.309+/
0.036 mg/g and from 0.279+/-0.031 to 2.300+/-0.060 mg/g, respectively. The main
phenolic constituents were chlorogenic acid, rutin and isoquercitrin, with
chlorogenic acid present in the highest concentrations, ranging from 3.104+/
0.191 to 10.050+/-0.143 mg/g. The antioxidant activity exhibited a tendency as
follows: Guangxi > Guangdong > Chongqing, except for two samples from Chongqing,
which showed the highest antioxidant activity. Based on our study, mulberry
leaves from Guangdong and Guangxi could be future sources of natural hypoglycemic
and antioxidant products.
PMID- 29944666
TI - Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells
(FSCs) through downregulation of transforming growth factor-beta1 (TGF-beta1).
AB - Treatment for musculoskeletal fibromatosis remains challenging. Surgical excision
for fibromatosis is the standard therapy but recurrence remains high.
Corticosteroids, an anti-fibrogenic compound, have been used to treat early stage
palmar fibromatosis, but the mechanism is unknown. We investigated the inhibitory
mechanism effect of corticosteroids in the murine model of fibromatosis nodule as
well as in cultured FSCs. Quantitative reverse transcription/polymerase chain
reaction (PCR) analysis and immunofluorescence (IF) staining for markers of
myofibroblasts (alpha-smooth muscle actin and type III collagen) were used to
examine the effect of dexamethasone on myofibroblasic differentiation of FSCs
both in vitro and in vivo. Transforming growth factor-beta1 (TGF-beta1) signaling
and its downstream targets were examined using western blot analysis. TGF-beta1
expression in FSCs before and after dexamethasone treatment was compared. In
addition, inhibition of TGF-beta1 expression was examined using RNA interference
(RNAi) on FSCs, both in vitro and in vivo. Treating FSCs with dexamethasone
inhibited FSCs' myofibroblastic differentiation in vitro. Treating FSCs with
dexamethasone before or after implantation further inhibited formation of
fibromatosis nodules. Dexamethasone suppressed expression of TGF-beta1 and
pSmad2/3 by FSCs in vitro. TGF-beta1 knockdown FSCs showed reducing
myofibroblastic differentiation both in vitro and in vivo. Finally, addition of
TGF-beta1 abolished dexamethasone-mediated inhibition of myofibroblastic
differentiation. Dexamethasone inhibits the myofibroblastic differentiated
potential of FSCs both in vitro and in vivo through inhibition of TGF-beta1
expression in FSCs. TGF-beta1 plays a key role in myofibroblastic
differentiation.
PMID- 29944662
TI - "Could you sit down please?" A qualitative analysis of employees' experiences of
standing in normally-seated workplace meetings.
AB - Office workers spend most of their working day sitting, and prolonged sitting has
been associated with increased risk of poor health. Standing in meetings has been
proposed as a strategy by which to reduce workplace sitting but little is known
about the standing experience. This study documented workers' experiences of
standing in normally seated meetings. Twenty-five participants (18+ years),
recruited from three UK universities, volunteered to stand in 3 separate, seated
meetings that they were already scheduled to attend. They were instructed to
stand when and for however long they deemed appropriate, and gave semi-structured
interviews after each meeting. Verbatim transcripts were analysed using Framework
Analysis. Four themes, central to the experience of standing in meetings, were
extracted: physical challenges to standing; implications of standing for meeting
engagement; standing as norm violation; and standing as appropriation of power.
Participants typically experienced some physical discomfort from prolonged
standing, apparently due to choosing to stand for as long as possible, and noted
practical difficulties of fully engaging in meetings while standing. Many
participants experienced marked psychological discomfort due to concern at being
seen to be violating a strong perceived sitting norm. While standing when leading
the meeting was felt to confer a sense of power and control, when not leading the
meeting participants felt uncomfortable at being misperceived to be challenging
the authority of other attendees. These findings reveal important barriers to
standing in normally-seated meetings, and suggest strategies for acclimatising to
standing during meetings. Physical discomfort might be offset by building
standing time slowly and incorporating more sit-stand transitions. Psychological
discomfort may be lessened by notifying other attendees about intentions to
stand. Organisational buy-in to promotional strategies for standing may be
required to dispel perceptions of sitting norms, and to progress a wider
workplace health and wellbeing agenda.
PMID- 29944664
TI - Preventability of maternal near miss and mortality in Rwanda: A case series from
the University Teaching Hospital of Kigali (CHUK).
AB - OBJECTIVE: Assess the primary causes and preventability of maternal near misses
(MNM) and mortalities (MM) at the largest tertiary referral hospital in Rwanda,
Kigali University Teaching Hospital (CHUK). METHODS: We reviewed records for all
women admitted to CHUK with pregnancy-related complications between January 1st,
2015 and December 31st, 2015. All maternal deaths and near misses, based on WHO
near miss criteria were reviewed (Appendix A). A committee of physicians actively
involved in the care of pregnant women in the obstetric-gynecology department
reviewed all maternal near misses/ pregnancy-related deaths to determine the
preventability of these outcomes. Preventability was assessed using the Three
Delays Model.[1] Descriptive statistics were used to show qualitative and
quantitative outcomes of the maternal near miss and mortality. RESULTS: We
identified 121 maternal near miss (MNM) and maternal deaths. The most common
causes of maternal near miss and maternal death were sepsis/severe systemic
infection (33.9%), postpartum hemorrhage (28.1%), and complications from
eclampsia (18.2%)/severe preeclampsia (5.8%)/. In our obstetric population, MNM
and deaths occurred in 87.6% and 12.4% respectively. Facility level delays
(diagnostic and therapeutic) through human error or mismanagement (provider
issues) were the most common preventable factors accounting for 65.3% of
preventable maternal near miss and 10.7% maternal deaths, respectively. Lack of
supplies, blood, medicines, ICU space, and equipment (system issues) were
responsible for 5.8% of preventable maternal near misses and 2.5% of preventable
maternal deaths. Delays in seeking care contributed to 22.3% of cases and delays
in arrival from home to care facilities resulted in 9.1% of near misses and
mortalities. Cesarean delivery was the most common procedure associated with
sepsis/death in our population. Previous cesarean delivery (24%) and
obstructed/prolonged labor (13.2%) contributed to maternal near miss and
mortalities. CONCLUSION: The most common preventable causes of MNM and deaths
were medical errors, shortage of medical supplies, and lack of patient
education/understanding of obstetric emergencies. Reduction in medical errors,
improved supply/equipment availability and patient education in early recognition
of pregnancy-related danger signs will reduce the majority of delays associated
with MNM and mortality in our population.
PMID- 29944665
TI - Did the Family Health Strategy have an impact on indicators of hospitalizations
for stroke and heart failure? Longitudinal study in Brazil: 1998-2013.
AB - INTRODUCTION: The objective was to analyze whether socioeconomic factors related
to the context and those related to the model of care-specifically the coverage
of primary care by the Family Health Strategy (ESF)-had an impact on
hospitalizations due to heart failure (HF) and stroke, in the State of Sao
Paulo/Brazil between 1998 and 2013. METHODS: A longitudinal ecological study
involving 645 municipalities was conducted in the state of Sao Paulo/Brazil from
1998 to 2013, using the Hospital Information System (SIH-DataSUS database). The
hospitalizations for primary care sensitive conditions: Stroke and heart failure
(HF) that correspond to the International Classification of Diseases (ICD 10):
I50, I63 to I67; I69, G45 to G46 were analyzed longitudinally during the period
indicated regarding the percentage of people covered by the Family Health Program
(PSF) adjusted for confounders (population size, gross domestic product -GDP and
human development index- HDI). RESULTS: There was a significant decrease in the
number of hospitalizations for heart failure and stroke per 10000 (inhabitants)
in the period (p <0.0001), with a significant relationship with increased
proportion of ESF (p <0.0001), and this remained significant even when possible
confounders (population size, GDP and HDI) were included in the model (p
<0.0001). CONCLUSIONS: GDP per capita was close to or higher than that if many
European countries, which shows the relevance of the study. The health care model
based on the Family Health Strategy positively impacted hospitalization
indicators for heart failure and stroke, indicating that this model is effective
in the prevention of primary care sensitive conditions.
PMID- 29944668
TI - The concurrent validity of the Internet Addiction Test (IAT) and the Mobile Phone
Dependence Questionnaire (MPDQ).
AB - Internet addiction and mobile phone addiction are both forms of technology
addiction, and thus would be expected to show similarities and differences. This
study investigated the association between the Internet Addiction Test (IAT) and
the Mobile Phone Dependence Questionnaire (MPDQ) as a test of concurrent
validity. Participants were 1,072 students aged between 9 and 18 years old (63%
male and 37% female) from three primary schools and three secondary schools in
Hong Kong. Correlations showed that scores on the two measures were moderately
correlated, providing further evidence of each measure's validity. Confirmatory
factor analysis that the IAT's factor structure was similar in both younger and
older samples, suggesting that it is developmentally appropriate for primary and
secondary school students. Latent Class Analysis showed that 4 classes or 5
classes are appropriate for IAT's score classification. ROC analyses showed
similar rates of participants with high scores on the IAT and on the MPDQ. The
outcomes have implications for the prevention and treatment of Internet and
mobile phone addiction. Future research can establish norms for different ages,
genders and cultural groups.
PMID- 29944669
TI - Optimal dynamic regimens with artificial intelligence: The case of temozolomide.
AB - We determine an optimal protocol for temozolomide using population variability
and dynamic optimization techniques inspired by artificial intelligence. We use a
Pharmacokinetics/Pharmacodynamics (PK/PD) model based on Faivre and coauthors
(Faivre, et al., 2013) for the pharmacokinetics of temozolomide, as well as the
pharmacodynamics of its efficacy. For toxicity, which is measured by the nadir of
the normalized absolute neutrophil count, we formalize the myelosuppression
effect of temozolomide with the physiological model of Panetta and coauthors
(Panetta, et al., 2003). We apply the model to a population with variability as
given in Panetta and coauthors (Panetta, et al., 2003). Our optimization
algorithm is a variant in the class of Monte-Carlo tree search algorithms. We do
not impose periodicity constraint on our solution. We set the objective of tumor
size minimization while not allowing more severe toxicity levels than the
standard Maximum Tolerated Dose (MTD) regimen. The protocol we propose achieves
higher efficacy in the sense that -compared to the usual MTD regimen- it divides
the tumor size by approximately 7.66 after 336 days -the 95% confidence interval
being [7.36-7.97]. The toxicity is similar to MTD. Overall, our protocol,
obtained with a very flexible method, gives significant results for the present
case of temozolomide and calls for further research mixing operational research
or artificial intelligence and clinical research in oncology.
PMID- 29944676
TI - Kupeantha (Coffeeae, Rubiaceae), a new genus from Cameroon and Equatorial Guinea.
AB - Two new coffee relatives (tribe Coffeeae, Rubiaceae), discovered during botanical
expeditions to Cameroon, are examined for generic placement, and the placement of
three previously known species (Argocoffeopsis fosimondi, A. spathulata and
Calycosiphonia pentamera) is reinvestigated using plastid sequence (accD-psa1,
rpl16, trnL-F) and morphological data. Seed biochemistry of the new species and
pollen micromorphology (only one of the two species) are also studied. Based on
the plastid sequence data, the new taxa are nested in a well-supported
monophyletic group that includes Argocoffeopsis and Calycosiphonia. Within this
clade, three well-supported subclades are recovered that are morphologically easy
to diagnose: (1) Calycosiphonia (excluding C. pentamera), (2) Argocoffeopsis
(excluding A. fosimondi and A. spathulata), and (3) a clade including the above
excluded species, in addition to the new species. Based on the results,
Kupeantha, a new genus of five species, is described, including two new
Critically Endangered taxa from the Highlands of Cameroon: Kupeantha ebo and K.
kupensis. Phytochemical analysis of Kupeantha seeds reveals compounds assigned as
hydroxycinnamic acid derivatives, amino acids and ent-kaurane diterpenoids;
caffeine was not detected. Kupeantha is the first new genus described in tribe
Coffeeae in 40 years.
PMID- 29944677
TI - Estimates of visual impairment and its causes from the National Eye Survey in
Malaysia (NESII).
AB - BACKGROUND: Population-based data on prevalence, causes of blindness and extent
of ophthalmological coverage is required for efficient implementation and
evaluation of ocular health programs. In view of the scarcity of prevalence data
for visual impairment and blindness in Malaysia, this study aims to estimate the
prevalence and causes of visual impairment (VI) in the elderly, using Rapid
Assessment of Avoidable Blindness (RAAB) survey technique. METHODS: Malaysia was
divided into six regions, with each region consisting of 50 clusters. Multistage
cluster sampling method was used and each cluster contained 50 residents aged 50
years and above. Eligible subjects were interviewed and pertinent demographic
details, barriers to cataract surgery, medical and ocular history was noted.
Subjects had visual acuity assessment with tumbling 'E' Snellen optotypes and
ocular examination with direct ophthalmoscope. The primary cause of VI was
documented. Results were calculated for individual zones and weighted average was
used to obtain overall prevalence for the country. Inter-regional and overall
prevalence for blindness, severe VI and moderate VI were determined. Causes of
VI, cataract surgical coverage and barriers to cataract surgery were assessed.
RESULTS: A total of 15,000 subjects were examined with a response rate of 95.3%.
The age and gender-adjusted prevalence of blindness, severe visual impairment and
moderate visual impairment were 1.2% (95% Confidence Interval: 1.0-1.4%), 1.0%
(95%CI: 0.8-1.2%) and 5.9% (5.3-6.5%) respectively. Untreated cataract (58.6%),
diabetic retinopathy (10.4%) and glaucoma (6.6%) were the commonest causes of
blindness. Overall, 86.3% of the causes of blindness were avoidable. Cataract
surgical coverage (CSC) in persons for blindness, severe visual impairment and
moderate visual impairment was 90%, 86% and 66% respectively. CONCLUSION:
Increased patient education and further expansion of ophthalmological services
are required to reduce avoidable blindness even further in Malaysia.
PMID- 29944670
TI - Supervised learning reveals circulating biomarker levels diagnostic of
hepatocellular carcinoma in a clinically relevant model of non-alcoholic
steatohepatitis; An OAD to NASH.
AB - Although cirrhosis is a key risk factor for the development of hepatocellular
carcinoma (HCC), mounting evidence indicates that in a subset of patients
presenting with non-alcoholic steatohepatitis (NASH) HCC manifests in the absence
of cirrhosis. Given the sheer size of the ongoing non-alcoholic fatty liver
disease (NAFLD) epidemic and the dismal prognosis associated with late-stage
primary liver cancer there is an urgent need for HCC surveillance in the NASH
population. Using serum levels of HCC biomarkers as vectors and biopsy-proven HCC
or no HCC as outputs / binary classifier, a supervised learning campaign was
undertaken to develop a minimally invasive technique for making a diagnosis of
HCC in a clinically relevant model of NASH. Adult mice randomized to control diet
or a fast food diet (FFD) were followed for up to 14 mo and serum level of a
panel of HCC-relevant biomarkers was compared with liver biopsies at 3 and 14 mo.
Both NAFLD Activity Score (NAS) and hepatic hydroxyproline content were elevated
at 3 and 14 mo on FFD. Picrosirius red staining of liver sections revealed a
filigree pattern of fibrillar collagen deposition with no cirrhosis at 14 mo on
FFD. Nevertheless, 46% of animals bore one or more tumors on their livers
confirmed as HCC in hematoxylin-eosin-stained liver sections. In this training
set, receiver operating characteristic (ROC) curves analysis for serum levels of
the HCC biomarkers osteopontin (OPN), alpha-fetoprotein (AFP) and Dickkopf-1
(DKK1) returned concordance-statistic/area under ROC curve of >= 0.89. Serum
levels of OPN (threshold, 218 ng/mL; sensitivity, 82%; specificity, 86%), AFP
(136 ng/mL; 91%; 97%) and DKK1 (2.4 ng/mL; 82%; 81%) diagnostic for HCC were
confirmed in a test set comprising mice on control diet or FFD and mice subjected
to hepatic ischemia-reperfusion injury. These data suggest that levels of
circulating OPN, AFP and DKK1 can be used to make a diagnosis of HCC in a
clinically relevant model of NASH.
PMID- 29944672
TI - Increased prevalence of eating disorders as a biopsychosocial implication of food
allergy.
AB - INTRODUCTION: The study evaluates the impact of biopsychosocial factors involved
in food allergy (FA) on the prevalence of eating disorders (ED). For the 5-year
follow-up studies, 75 participants (aged 1-14 years) with early-onset FA and 81
healthy peers were included. METHOD: Participants were diagnosed with FA using
antibody/cytokine content immunoassay tests. Medical history, including BMI z
scores, was completed using data obtained in response to a validated allergic
questionnaire that incorporated the SCOFF and EAT-8 screening questionnaires for
ED. FA was confirmed if total IgE was elevated, specific sIgE to food allergens
exceeded 0.7 kUA/L and if manifestations were observed. Screening for ED was
considered positive if two or more SCOFF and EAT-8 items were confirmed. RESULTS:
In the FA+ group, 50% of female participants and 6.7% of their healthy female
peers reported ED. An ED+ result was more frequent in FA+ individuals than in
their healthy peers (p = 0.046) although the association is weak. In the FA+/ED+
group, 25.3% of the participants were underweight, and 14.7% were overweight
compared to their peers where this reached respectively 4.2% and 2.8% (p<0.005).
74% of the FA+/ED+ individuals reported elimination diet implementation and only
15% declared it was medically consulted. The prevalence of ED in the FA+ male
group was consistently correlated with lack of confidence in FA issues (r =
0.5424) and in the FA+ female group with applied medical procedures (r = 0.7069;
p<0.005). CONCLUSION: These findings suggest that participants with FA especially
struggling with lack of confidence in FA issues and those following an
uncontrolled, restrictive elimination diet are more prone to food aversion and ED
than their healthy peers. Applied procedures are necessary, and their neglect is
associated with FA deterioration; however, the possibility of ED and
biopsychosocial implications development should not be underestimated.
PMID- 29944675
TI - The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in
England.
AB - OBJECTIVES: Electronic health records (EHR) might be a useful resource to study
the risk factors and clinical care of people with dementia. We sought to
determine the diagnostic validity of dementia captured in linked EHR. METHODS AND
FINDINGS: A cohort of adults in linked primary care, hospital, disease registry
and mortality records in England, [CALIBER (CArdiovascular disease research using
LInked Bespoke studies and Electronic health Records)]. The proportion of
individuals with dementia, Alzheimer's disease, vascular and rare dementia in
each data source was determined. A comparison was made of symptoms and care
between people with dementia and age-, sex- and general practice-matched
controls, using conditional logistic regression. The lifetime risk and prevalence
of dementia and mortality rates in people with and without dementia were
estimated with random-effects Poisson models. There were 47,386 people with
dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare
dementia. Seventy-four percent of cases had corroborating evidence of dementia.
People with dementia were more likely to live in a deprived area (conditional OR
1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment
(cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression
(cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The
lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9%
(95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia
increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed
in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58). CONCLUSIONS:
Most people with a record of dementia in linked UK EHR had some corroborating
evidence for diagnosis. The estimated 10-year risk of dementia was higher than
published population-based estimations. EHR are therefore a promising source of
data for dementia research.
PMID- 29944673
TI - Diagnostic accuracy of macular ganglion cell-inner plexiform layer thickness for
glaucoma detection in a population-based study: Comparison with optic nerve head
imaging parameters.
AB - AIMS: To determine the diagnostic performance of macular ganglion cell-inner
plexiform layer (GCIPL) thickness measured by spectral-domain optical coherence
tomography (SD-OCT) for glaucoma detection in a Chinese population in comparison
with optic nerve head (ONH) and retinal nerve fiber layer (RNFL) parameters
measured by both SD-OCT and Heidelberg Retina Tomography 3 (HRT-3). METHODS:
Adults aged 40 to 80 years were recruited from the population-based study (n =
3353, response rate 72.8%). Macular cube 200x200 scan was performed with Cirrus
SD-OCT (version 6.0, Carl Zeiss Meditec Inc, Dublin, CA) for GCIPL thickness
measurement. ONH and RNFL imaging was performed with Cirrus SD-OCT and HRT-3
(Heidelberg Engineering, Heidelberg, Germany). Glaucoma was defined according to
International Society for Geographical and Epidemiological Ophthalmology
criteria. RESULTS: In total, 86 eyes of 60 subjects with glaucoma and 1709 eyes
of 1001 non-glaucoma participants were included. The best performing parameters
for Cirrus SD-OCT GCIPL, Cirrus SD-OCT ONH and HRT-3 were minimum GCIPL thickness
(Area under receiver-operating curve [AUC] = 0.89, 95% CI 0.83-0.95), vertical
cup-disc ratio (CDR) (AUC = 0.94, 0.91-0.98) and vertical CDR (AUC = 0.86, 0.81
0.92), respectively. At 85% specificity, vertical CDR measured using Cirrus OCT
ONH scan showed the highest sensitivity (88.64%, 95% CI 75.4-96.2) compared to
minimum GCIPL thickness with sensitivity of 60.53% (95% CI 46.4-73.0) (p<0.001).
Inferior RNFL thickness (AUC = 0.84, 95% CI 0.91-0.97) measured by Cirrus SD-OCT
was also superior to Cirrus SD-OCT GCIPL (p<0.007). CONCLUSIONS: The diagnostic
performance of macular GCIPL scan is inferior compared to vertical CDR measured
by Cirrus OCT ONH scan. Cirrus OCT ONH scan showed the best ability in detecting
glaucoma in a Chinese population, suggesting it could be a good glaucoma
screening tool in an Asian population.
PMID- 29944678
TI - High CD4 counts associated with better economic outcomes for HIV-positive adults
and their HIV-negative household members in the SEARCH Trial.
AB - BACKGROUND: Country decisions to scale-up "test and treat" approaches for HIV
depend on consideration of both the health and economic consequences of such
investments. Evidence about economic impacts of expanded antiretroviral therapy
(ART) provision is particularly relevant for decisions regarding foreign
assistance levels for HIV/AIDS programs. We used baseline data from the
Sustainable East Africa Research in Community Health (SEARCH) cluster randomized
controlled trial in Kenya and Uganda to examine the association between HIV
status, CD4+ T-cell counts, viral suppression, and multiple indicators of
economic well-being. METHODS AND FINDINGS: Socio-economic surveys were conducted
in households with HIV-positive and HIV-negative adults sampled after a census of
32 communities participating in the SEARCH trial (NCT01864603). Data were
obtained for 11,500 individuals from 5,884 households in study communities.
Participants were stratified based on their own HIV status as well as CD4 counts
and viral suppression status if they were HIV-positive. HIV-negative participants
residing in households with no HIV-positive adults were considered separately
from HIV-negative participants residing in households with >=1 HIV-positive
adult. Generalized estimating equation models were used to examine the
relationship between HIV status, CD4 counts, ART, viral suppression, and outcomes
of employment, self-reported illness, lost time from usual activities due to
illness, healthcare utilization, health expenditures, and hospitalizations. In
all models, HIV-negative participants in households with no HIV-positive persons
were the reference group. There was no significant difference in the probability
of being employed between HIV-positive participants with CD4>500 and the
reference group of HIV-negative participants residing in households with no HIV
positive adults (marginal effect, ME, 1.49 percentage points; 95% confidence
interval, CI, -1.09, 4.08). However, HIV-positive participants with CD4 351-500
were less likely to be employed than the reference group (ME -4.50, 95% CI -7.99,
-1.01), as were HIV-positive participants with CD4 <=350 (ME -7.41, 95% CI
10.96, -3.85). Similarly, there was no significant difference in employment
likelihood between HIV-negative participants who resided in households with a
CD4>500 HIV-positive person and the reference group (ME -1.78, 95% CI -5.16,
1.59). HIV-negative participants residing with an HIV-positive person with CD4
351-500, however, were less likely to be employed than the reference group (ME
7.03, 95% CI -11.49, -2.57), as were people residing with a household member with
CD4 <=350 (ME -6.28, 95% CI -10.76, -1.80). HIV-positive participants in all CD4
categories were more likely to have lost time from usual activities due to
illness and have incurred healthcare expenditures. Those with CD4>500 had better
economic outcomes than those with CD4 351-500, even among those not virally
suppressed (p = 0.004) and not on ART (p = 0.01). CONCLUSIONS: Data from a large
population-representative sample of households in east Africa showed a strong
association between the health of HIV-positive persons and economic outcomes. The
findings suggest there may be economic benefits associated with maintaining high
CD4 counts, both for HIV-positive persons and their HIV-negative household
members. The association of high CD4 counts with improved outcomes is consistent
with the hypothesis that early ART initiation can avert declines in employment
and other economic outcomes. Prospective longitudinal evaluation is needed to
assess the causal impact of early ART initiation on economic functioning of
households.
PMID- 29944671
TI - Exploring the role of NCCR variation on JC polyomavirus expression from dual
reporter minicircles.
AB - JC virus (JCV), a ubiquitous human polyomavirus, can cause fatal progressive
multifocal leukoencephalopathy (PML) in immune compromised patients. The viral
genome is composed of two conserved coding regions separated by a highly variable
non-coding control region (NCCR). We analyzed the NCCR sequence from 10 PML JCV
strains and found new mutations. Remarkably, the NCCR f section was mutated in
most cases. We therefore explored the importance of this section in JCV
expression in renal (HEK293H) and glioblastoma (U-87MG) cell lines, by adapting
the emerging technology of DNA minicircles. Using bidirectional fluorescent
reporters, we revealed that impaired NCCR-driven late expression in glioblastoma
cells was restored by a short deletion overlapping e and f sections. This study
evidenced a relevant link between JCV NCCR polymorphism and cell-type dependent
expression. The use of DNA minicircles opens new insights for monitoring the
impact of NCCR variation.
PMID- 29944674
TI - Computational quantum chemistry, molecular docking, and ADMET predictions of
imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties.
AB - Schistosomiasis affects million people and its control is widely dependent on a
single drug, praziquantel. Computational chemistry has led to the development of
new tools that predict molecular properties related to pharmacological potential.
We conducted a theoretical study of the imizadole alkaloids of Pilocarpus
microphyllus (Rutaceae) with schistosomicidal properties. The molecules of
epiisopiloturine, epiisopilosine, isopilosine, pilosine, and macaubine were
evaluated using theory models (B3lyp/SDD, B3lyp/6-31+G(d,p), B3lyp/6
311++G(d,p)). Absorption, distribution, metabolization, excretion, and toxicity
(ADMET) predictions were used to determine the pharmacokinetic and
pharmacodynamic properties of the alkaloids. After optimization, the molecules
were submitted to molecular docking calculations with the purine nucleoside
phosphorylase, thioredoxin glutathione reductase, methylthioadenosine
phosphorylase, arginase, uridine phosphorylase, Cathepsin B1 and histone
deacetylase 8 enzymes, which are possible targets of Schistosoma mansoni. The
results showed that B3lyp/6-311++G(d,p) was the optimal model to describe the
properties studied. Thermodynamic analysis showed that epiisopiloturine and
epiisopilosine were the most stable isomers; however, the epiisopilosine ligand
achieved a superior interaction with the enzymes studied in the molecular docking
experiments, which corroborated the results of previous experimental studies on
schistosomiasis.
PMID- 29944679
TI - Heterogeneity of adolescent health risk behaviors in rural western China: A
latent class analysis.
AB - BACKGROUND: Adolescent health risk behaviors are a public health priority given
their prevalence and their associations with chronic diseases and life quality in
adulthood. This study examined the heterogeneity of adolescent health risk
behaviors and the associations between demographic characteristics and subgroup
membership in rural western China. METHODS: In fall 2015, 2805 students from
rural middle schools in Sichuan Province were surveyed using the Health-Related
Behavior Questionnaire for Adolescents. Latent class analysis (LCA) was used to
identify subgroups of adolescents with distinct patterns of health risk
behaviors. Differences in class membership related to selected demographic
characteristics were examined using multinomial logistic regression analysis.
RESULTS: A four-class model emerged: (1) high-risk group (n = 108, 4.0%), (2)
high-physical-inactivity and suicide-risk group (n = 340, 12.1%), (3) moderate
risk group (n = 897, 32.0%), and (4) low-risk group (n = 1460, 52.1%). The
multinomial logistic regression analysis revealed that boys and adolescents with
poor parental relationships and high allowances (spending money) were
significantly more likely to be in the high-risk group than the low-risk group.
CONCLUSIONS: Adolescents in rural western China are a heterogeneous population
requiring different tailored and effective interventions.
PMID- 29944681
TI - Are we choosing the right flagships? The bird species and traits Australians find
most attractive.
AB - Understanding what people like about birds can help target advocacy for bird
conservation. However, testing preferences for characteristics of birds is
methodologically challenging, with bias difficult to avoid. In this paper we test
whether preferred characteristics of birds in general are shared by the
individual bird species the same people nominate as being those they consider
most attractive. We then compare these results with the birds which appear most
frequently in the imagery of conservation advocates. Based on a choice model
completed by 638 general public respondents from around Australia, we found a
preference for small colourful birds with a melodious call. However, when the
same people were asked which five birds they found most attractive, 48% named no
more than three, mostly large well-known species. Images displayed by a leading
Australian bird conservation organisation also favoured large colourful species.
The choice model results suggest conservation advocates can promote a much wider
range of bird types as flagships, particularly smaller species that might
otherwise be neglected.
PMID- 29944683
TI - Validity of inferring size-selective mortality and a critical size limit in
Pacific salmon from scale circulus spacing.
AB - Size-selective mortality owing to lack of energy reserves during the first marine
winter has been suggested to be a result of juvenile salmon failing to reach a
critical size or condition by the end of their first marine summer and not
surviving the following winter due to this presumed energy deficit. This
hypothesis implies strong size dependency of mortality, and is subject to
empirical data support for acceptance. Scale circulus spacing has been
interpreted as an index for body size, and we reviewed the effect of size
selective mortality with a knife-edge mortality function on descriptive
statistics for a scale circulus spacing index (SCSI). In order to invoke size
selection as an important driver of mortality during the first year of ocean
rearing, it is necessary to demonstrate not only that size-selective mortality is
directed towards the smaller members of the population, but that the selective
nature of the mortality can account for a substantial portion of the observed
mortality. If the assumption is made that a random sample of a single juvenile
population has been obtained, then studies that employ a SCSI to infer size
selective mortality coupled with a critical size limit must demonstrate a shift
toward larger values of the SCSI, but also a concomitant reduction in the
variance and range of the SCSI and an increase in the skewness and kurtosis of
the SCSI values. Through simulation we found that the percentage of adults that
displayed a SCSI value greater than the maximum observed in the juvenile sample
was highly dependent on the initial juvenile sample size and size-selective
mortality rate. Geographical distributions of juvenile Pacific salmon can be
stratified by size, with larger individuals migrating earlier from local ocean
entry locations than smaller individuals, and thus differential timing migration
of juveniles based upon body size prior to the collection of the marine juvenile
sample may be a more plausible explanation of published trends in the SCSI,
rather than invoking substantial size-selective mortality and a critical size
limit.
PMID- 29944684
TI - Identification of endophytes with biocontrol potential from Ziziphus jujuba and
its inhibition effects on Alternaria alternata, the pathogen of jujube shrunken
fruit disease.
AB - Endophytic strains were isolated from different parts of a healthy "Dongzao"
jujube (Ziziphus jujuba Mill. 'Dongzao') to find biocontrol agents against jujube
shrunken-fruit disease caused by Alternaria alternata. The strains were screened
using A. alternata strain CN193 as the target pathogen. The nutrient competition
for all isolates was studied using the dual culture, and their inhibitive
capability was tested by measuring the inhibition width of filter paper disks
with filtrate. Influence of filtrate from the selected strains with strong
inhibition of mycelial growth on spore germination was studied with hanging drop
method on concavity slides. Colonization in the jujube leaves was assayed using a
rifampicin-resistant mutant of strain St-zn-34 as the screening marker. Strains
were identified based on their morphological, physiological, and biochemical
characteristics, 16S rDNA sequencing, and phylogenetic analysis. A total of 81
endophytic strains were isolated from the stems, leaves, flowers, and fruits of
winter jujube. Among these isolates, 14 strains showed strong antagonism against
A. alternata. Further study showed that the filtrate of strains St-zn-9 and St-zn
34 could inhibit the mycelial growth of A. alternata, and the widths of their
inhibition zone reached 6.14+/-0.03 mm and 8.27+/-0.09 mm, respectively. However,
strain St-zn-34 showed stronger inhibition on spore germination than strain St-zn
9. St-zn-34 could significantly reduce the spore germination rate of A.
alternata, and the spore did not germinate at all or the germ tube was very
short. A rifampicin resistant-derivative of wild-type strain St-zn-34, which was
designated as St-zn-34r, was obtained by transferring the strains to media with
stepwise-increased rifampicin. Colonization assays indicated that St-zn-34r could
colonize in jujube leaves, and the population of St-zn-34r was 1.2*103 CFU/g FW
after inoculation for 30 days. Except for its salt tolerance, St-zn-34 was the
closest to those of Bacillus subtilis. Thus, the strain was identified as B.
subtilis.
PMID- 29944682
TI - Diagnostic accuracy of the loop-mediated isothermal amplification assay for
extrapulmonary tuberculosis: A meta-analysis.
AB - BACKGROUND: Loop-mediated isothermal amplification (LAMP) is used to detect
pulmonary tuberculosis (PTB); however, the diagnostic accuracy of the LAMP assay
for extrapulmonary tuberculosis (EPTB) is unclear. We performed a meta-analysis
to evaluate the performance of LAMP in the detection of EPTB. METHODS: We
searched PubMed, EMBASE, the Cochrane Library, China National Knowledge
Infrastructure (CNKI), and the Wanfang database for studies published before Sep
16, 2017. We reviewed studies and compared the performance of LAMP with that of a
composite reference standard (CRS) and culture for clinically suspected EPTB. We
used a bivariate random-effects model to perform meta-analyses and used meta
regression and subgroup analysis to analyze sources of heterogeneity. RESULTS:
Fourteen articles including 24 independent studies (16 compared LAMP to CRS, 8 to
culture) of EPTB were identified. LAMP showed a pooled sensitivity of 77% (95%
confidence interval (CI) 68-85), specificity of 99% (95% CI 96-100), and area
under SROC curves (AUC) of 0.96 (95% CI 0.94-0.97) against CRS. It showed a
pooled sensitivity of 93% (95% CI 88-96), specificity of 77% (95% CI 64-86), and
AUC of 0.94 (95% CI 0.92-0.96) against culture. The pooled sensitivity,
specificity, and AUC of MPB64 LAMP were 86% (95% CI 86-86), 100% (95% CI 100
100), and 0.97 (95% CI 0.95-0.98), respectively, and those of IS6110 LAMP were
75% (95% CI 64-84), 99% (95% CI 90-100), and 0.91 (95% CI 0.88-0.93),
respectively, compared with CRS. CONCLUSIONS: These results suggest good
diagnostic efficacy of LAMP in the detection of EPTB. Additionally, the
diagnostic efficacy of MPB64 LAMP was superior to that of IS6110 LAMP.
PMID- 29944680
TI - Different composition of intraocular immune mediators in Posner-Schlossman
Syndrome and Fuchs' Uveitis.
AB - Posner-Schlossman-Syndrome (PSS) is clinically characterized by acute, recurrent,
mild, unilateral uveitis anterior accompanied by elevated intraocular pressure
(IOP). Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder,
involving anterior uvea and vitreous. The clinical findings show remarkable
similarities as well as differences. In our study, we determine the composition
of immune mediators in aqueous humor of patients with PSS and FU and evaluate if
immune mediators play a crucial role in specific viral intraocular inflammation
and IOP rises. Aqueous humor samples from 81 uveitis patients (= eyes) presenting
with either PSS or FU were collected at one time point. Local intraocular
antibody synthesis to rubella virus was confirmed in 65 patients, whereas 16 were
tested positively for human cytomegalovirus. Thirteen patients with PSS and 10
patients with FU were treated with glaucoma medications. Additionally, 11
cataract patients acted as control group. Immune mediator concentrations were
measured by Bio-Plex Pro assay. We observed in both PSS (IFN-gamma: 174.9 pg/mL;
TNF-alpha: 25.1 pg/mL) and FU (IFN-gamma: 25.4 pg/mL; TNF-alpha: 27.2 pg/mL)
groups a significantly increased level of T-helper 1 immune mediators compared to
controls (IFN-gamma, TNF-alpha: 0 pg/mL) [median]. Notably, PSS patients (IL-1RA:
73.4 pg/mL; IL-8: 199.4 pg/mL; IL-10: 33.4 pg/mL; IP-10: 126350 pg/mL) showed a
stronger and more active ocular inflammatory response, than FU patients (IL-1RA:
4.3 pg/mL; IL-8: 72.4 pg/mL; IL-10: 1.6 pg/mL; IP-10: 57400 pg/mL). Furthermore,
a negative correlation between mediators and IOP was seen in the PSS group,
potentially caused by acetazolamide-treatment. Our findings show that immune
mediators play a crucial role in specific viral intraocular inflammation and
influence IOP levels. Remarkable similarities but also significant differences of
immune mediator concentrations are apparent in PSS compared to FU. High
concentrations of IL-1RA, IL-8, IL-10, and IP-10 correlate with active
inflammation in PSS, while FU may trigger chronic inflammation. Our data also
substantiated a very similar composition of cytokines in those patients from the
PSS group suffering from ocular hypertension and thus offers a potential
explanation model for a negative correlation between mediators and IOP.
PMID- 29944685
TI - Genomic and phenotypic characterization of Borrelia afzelii BO23 and Borrelia
garinii CIP 103362.
AB - In recent years, the number of Lyme disease or borreliosis cases in Eurasia has
been dramatically increasing. This tick-borne disease is caused by Borrelia
burgdorferi sensu lato, which includes B. burgdorferi sensu stricto, the main
species found in North America, and B. afzelii and B. garinii, which are
primarily responsible for the disease in Eurasia. Currently, research on Lyme
disease has focused mainly on B. burgdorferi while B. afzelii and B. garinii,
which cause disease with distinctly different symptoms, are less studied. The
purpose of this study is to evaluate B. afzelii BO23 and B. garinii CIP 103362 as
model organisms to study Eurasian Lyme disease. To begin our analyses, we
sequenced, annotated the chromosomes of both species and compared them to B.
burgdorferi strain B31. We also assayed shuttle vector, pBSV2, for transformation
efficacy and demonstrated that these strains can be cultured on solid media. In
addition, we characterized how physicochemical parameters (e.g., oxygen,
osmolarity, oxidative stress) affect both growth and motility of the bacteria.
Finally, we describe each strain's antibiotic susceptibility and accessed their
ability to infect mice. In conclusion, B. afzelii BO23 was more practical for in
vitro and in vivo studies than B. garinii CIP 103362.
PMID- 29944686
TI - trnL outperforms rbcL as a DNA metabarcoding marker when compared with the
observed plant component of the diet of wild white-faced capuchins (Cebus
capucinus, Primates).
AB - DNA metabarcoding is a powerful tool for assessing the diets of wild animals, but
there is no clear consensus on which proposed plant barcoding marker is most
suitable for dietary analysis. This study compares two DNA plant barcoding
markers that are commonly used for dietary analyses from degraded DNA, rbcL and
trnL, to detailed dietary observations of wild white-faced capuchins (Cebus
capucinus). Observational dietary data and fecal samples (n = 170) were collected
for one year from a group of individually recognizable monkeys at La Suerte
Biological Field Station, Costa Rica. DNA was extracted and portions of the rbcL
and trnL chloroplast were amplified and sequenced on the Illumina MiSeq platform.
Sequences were analyzed using obitools. Of the two barcoding markers tested, trnL
yielded greater numbers of sequences with equal sequencing effort, higher
resolution taxonomic identifications (albeit with a larger reference database),
and identified a greater number of families also found in the observed diet.
There was no relationship between observed capuchin feeding behavior and dietary
composition based on either sequence occurrence or relative abundance of
sequences using rbcL as a marker. However, dietary composition based on the
relative abundance of trnL sequences was significantly positively associated with
the observed percentage of feeding and foraging time capuchins' spent on each
plant species. Additionally, in 35% of cases, the relative abundance of trnL
sequences assigned to particular plant families in fecal samples was highly
positively correlated with time spent consuming plants from those same families.
Our results indicate that trnL is a more robust DNA metabarcoding marker for
plant dietary analysis and may potentially be used to quantitatively assess
differences in diet within or between species.
PMID- 29944687
TI - Diagnostic performance of plasma and urine neutrophil gelatinase-associated
lipocalin, cystatin C, and creatinine for acute kidney injury in burn patients: A
prospective cohort study.
AB - BACKGROUND: Diagnosing acute kidney injury quickly is imperative since it is
known as an independent risk factor for mortality in burn patients. We evaluated
the diagnostic power of creatinine, cystatin, serum and urine neutrophil
gelatinase-associated lipocalin at different time periods and observed the
changes from baseline for each biomarker. METHODS: This was a prospective
observation study from January 2015 to February 2016. A total of 84 patients were
enrolled consecutively. Serum creatinine, serum cystatin C, and serum and urine
neutrophil gelatinase-associated lipocalin were measured at admission, 7th, 14th,
21st, and 28th days after admission. All samples were collected until acute
kidney injury developed. RESULTS: Acute kidney injury developed in 35 patients.
The mean age was 49.6 years with a male predominance. The median urine neutrophil
gelatinase-associated lipocalin was the lowest (11.6 ng/dL) at admission, and the
highest at 85.5 ng/dL on day 7. Mean creatinine level was the highest (0.88
mg/dL) at admission and the median creatinine level was the lowest (0.56 mg/dL)
on the 14th day. The area under the curve of creatinine levels was the highest
with 0.857 during the 1st week. The area under the curve of urine neutrophil
gelatinase-associated lipocalin was the highest with 0.803 during the 5th week.
CONCLUSIONS: Within 1 week of acute kidney injury, creatinine level was the
optimal biomarker for diagnosis while urine neutrophil gelatinase-associated
lipocalin showed better diagnostic performance following the 4- week period.
PMID- 29944688
TI - Associated morphometric and geospatial differentiation among 98 species of stone
oaks (Lithocarpus).
AB - Two fruit types can be distinguished among stone oaks (Lithocarpus) species: the
'acorn' (AC) and the 'enclosed receptacle' (ER) types. Our morphometric analysis
of 595 nuts from 98 species (one third of all Lithocarpus spp.) found substantial
transition in mechanical protection of the seed between two woody fruit tissues
(exocarp and receptacle) of two fruit types. AC fruits were smaller in seed and
fruit size and the thin brittle exocarp largely enclosed the seed, whereas ER
fruits were larger and the seed was mostly enclosed by thick woody receptacle
tissue. The differences in these two tissues were considerably greater between
compared to within fruit type and species. Geospatial distribution showed that
seed size of all examined species increased with elevation and decreased with
latitude, the physical defense increased with both elevation and latitude, and ER
fruit species were more common at higher elevation. The two fruit types represent
distinct suites of associated traits that respond differently to the various
biotic and abiotic factors associated with geographic variation, profoundly
impacting the evolution of the two fruit types. The co-occurrence of two fruit
types in the same forest could be a consequence of distinct fruit and animal
interactions.
PMID- 29944690
TI - Do long-term care services match population needs? A spatial analysis of nursing
homes in Chile.
AB - Chile is experiencing a period of rapid aging, which increases the need of long
term care services in the country. Nursing homes have been the traditional
alternative to deal with the increase of elderly population in the country, with
services supplied by a mix of for-profit and nonprofit providers. Additionally,
population exhibits a high degree of geographical concentration. The study aims
to identify the determinants of the geographical location of nursing homes in
Chile at municipality level. The analysis takes into account the different
location criteria for different types of nursing homes as well as potential
spatial effects. The paper uses spatial analysis tools to identify clusters of
nursing homes and population characteristics and to estimate the determinants of
nursing homes availability and coverage in the country. The analysis-based on
spatial global and local tests, and spatial autoregressive models- show the
existence of clusters of nursing homes as well as clusters of municipalities
according to elderly population, income, poverty, population density, and public
health insurance coverage. Residuals from ordinary least squares regressions were
spatially autocorrelated, showing the need of using spatial models. Estimations
show that availability and coverage of nursing homes are positively related with
municipality income, and that for-profit and nonprofit facilities respond
differently to different factors. A negative coefficient was found for poverty in
nonprofit nursing homes, raising doubts about the effectiveness of giving public
subsidies to incentive the installation of facilities in areas with high needs
and low income.
PMID- 29944689
TI - A novel growth function incorporating the effects of reproductive energy
allocation.
AB - Ontogenetic growth functions provide basic information in biological and
ecological studies. Various growth functions classified into the Putter model
have been used historically, regardless of controversies over their
appropriateness. Here, we present a novel growth function for fish and aquatic
organisms (generalised q-VBGF) by considering an allocation schedule of
allometrically produced surplus energy between somatic growth and reproduction.
The generalised q-VBGF can track growth trajectories in different life history
strategies from determinate to indeterminate growth by adjusting the value of the
'growth indeterminacy exponent' q. The timing of maturation and attainable body
size can be adjusted by the 'maturation timing parameter' tau while maintaining a
common growth trajectory before maturation. The generalised q-VBGF is a
comprehensive growth function in which exponentials in the traditional
monomolecular, von Bertalanffy, Gompertz, logistic, and Richards functions are
replaced with q-exponentials defined in the non-extensive Tsallis statistics, and
it fits to actual data more adequately than these conventional functions. The
relationship between the estimated parameter values tau and rq forms a unique
hyperbola, which provides a new insight into the continuum of life history
strategies of organisms.
PMID- 29944691
TI - New SIMS U-Pb age constraints on the largest lake transgression event in the
Songliao Basin, NE China.
AB - The largest lake transgression event (LTE) associated with lake anoxic events
(LAE) and periodic seawater incursion events (SWIE) in the Songliao Basin,
northeastern China, occurred during deposition of the Cretaceous Nenjiang
Formation. The Yaojia-Nenjiang Formation boundary (YNB) marks the beginning of
the LTE, as well as LAE and SWIE. However, there is an absence of direct
radioisotopic dating, and therefore the age of the YNB, as well as the beginning
of LTE, together with their relationship with other geological events, is
strongly debated. Here we present a new SIMS U-Pb zircon age from the lowermost
Nenjiang Formation. The bentonite bed located 9.88 m above the YNB of the X1-4
borehole was analyzed. Twenty-five analyses of 25 zircons were conducted, which
produced a weighted mean age of 85.5+/-0.6 Ma (MSWD = 0.87). Based on the average
sediment accumulation rate, the age of the YNB is suggested to be 85.7 Ma,
indicating that the LTE began in the Early Santonian. The new ages provide a
precise chronostratigraphic framework for climatic and geological events. Our new
results imply that the beginning of the LTE, LAE and SWIE occurred almost
simultaneously with short-term sea level rise, and probably had a close
relationship with OAE3.
PMID- 29944692
TI - Development of the Taiwanese version of the Health Enhancement Lifestyle Profile
(HELP-T).
AB - OBJECTIVES: To develop and validate a Taiwanese version of the Health Enhancement
Lifestyle Profile (HELP-T) for community-dwelling older Taiwanese adults (>= 55
years). METHODS: The original Health Enhancement Lifestyle Profile (HELP) is a 56
item self-report questionnaire measuring various aspects of health-related
lifestyles in older adults. The standard cultural-adaptation procedure was used
for questionnaire translation and modification. A field test was conducted for
culturally specific item selection, rating-scale analysis, and psychometric
validation of the HELP-T in a sample of 274 community-dwelling older adults via
classical test theory. RESULTS: The 59-item HELP-T is culturally adapted from the
original 56-item HELP. The original 6-point rating scale was modified to a 3
point scale for easy use by Taiwanese older adults. The HELP-T had good internal
consistency (Cronbach's alpha = 0.82). The test-retest reliability for the total
score was high (0.92), and moderate to high (range: 0.57-0.92) for subscales. The
construct validity was supported by the significant correlations between each
subscale and the total score (Spearman's rho = 0.41-0.67, p < 0.0001) and by the
ability of the scores to significantly discriminate between participants with
different levels of self-rated health (p = 0.0001). CONCLUSIONS: The HELP-T is a
suitable clinical tool for assessing and monitoring lifestyle risk factors,
establishing client-centered lifestyle intervention goals, and determining the
outcomes of lifestyle interventions.
PMID- 29944693
TI - Functional connectivity in ruminants: A generalized state-dependent modelling
approach.
AB - Animal behaviour is increasingly seen as an important component in maintaining
functional connectivity between patches in fragmented landscapes. However, models
that explicitly incorporate behavioural trade-offs are rarely applied to
landscape planning problems like connectivity. The aim of this study was to
explore how state-dependent behaviour influenced functional connectivity between
patches from a theoretical perspective. We investigated how inter-patch distances
influenced functional connectivity using a dynamic state variable model
framework. The decision making process of an individual ruminant facing fitness
trade-offs in staying in its patch of origin or moving to another patch at
various distances were explicitly modelled. We incorporated energetic costs and
predation costs of feeding, ruminating, and resting while in the patch and for
transit between patches based on inter-patch distance. Functional connectivity
was maintained with isolated patches when they offered high intake and the
inactivity of rumination associated with rapid gut fill resulted in reduced
predation risk. Nevertheless, individuals in high energetic state often would
forgo moving to another patch, whereas individuals in poor energetic states were
forced to accept the cost of movement to best meet their requirements in the
distant patch. The inclusion of state-dependent behavioural models provides
important insights into functional connectivity in fragmented landscapes and
helps integrate animal behaviour into landscape planning. We discuss the
consequences of our findings for landscape planning to show how the approach
provides a heuristic tool to assess alternative scenarios for restoring landscape
functional connectivity.
PMID- 29944694
TI - Cervical cancer screening among incarcerated women.
AB - BACKGROUND: Women with a history of incarceration bear a disproportionate burden
of cervical disease and have special characteristics that affect their intent
and/or ability to adhere to cervical screening and follow-up recommendations. The
goal of this study was to identify factors associated with cervical cancer
screening and screening outcomes among incarcerated women. METHODS: We applied a
framework of predisposing factors, enabling factors and population-specific
characteristics that could impact screening behaviors and outcomes for this
population. We used bivariate chi-square tests and Wilcoxon signed-rank tests to
analyze data previously collected from 290 incarcerated women. RESULTS: Cervical
cancer screening belief score, as a predisposing factor, was associated with
women who had an up-to-date Pap test and who had a cervical cancer diagnosis ever
in their life. Both a sexual history containing high-risk behaviors and a history
of abuse, population-specific factors, were each associated with having had an
abnormal pap; mental health, incarceration, and substance use histories were each
associated with having a diagnosis of cervical cancer. CONCLUSIONS: The
significant differences in outcomes for these population-specific factors suggest
the need for a health services approach that addresses the challenges to the
cervical cancer preventive health needs of incarcerated women. IMPLICATIONS FOR
PRACTICE: Providers working with vulnerable populations such as women who have
been incarcerated should be aware that their risk histories have an influence on
their follow-up behaviors. These women will need extra support for cervical
cancer screening and follow-up care.
PMID- 29944695
TI - Pneumococcal carriage and serotype distribution among children with and without
pneumonia in Mozambique, 2014-2016.
AB - BACKGROUND: Pneumococcal colonization is a precursor to pneumonia, and
pneumococcal conjugate vaccines (PCV) can decrease vaccine-type (VT)
colonization. Pneumococcal colonization studies are traditionally done among
healthy children in the community; however, VT colonization prevalence may differ
between these children and those with pneumonia. We assessed overall and VT
pneumococcal colonization and factors associated with colonization among children
with and without pneumonia after Mozambique introduced 10-valent PCV (PCV10) in
2013. METHODS: We used data from ongoing pneumonia surveillance in children aged
<5 years and from cross-sectional nasopharyngeal colonization surveys conducted
in October 2014 -April 2015 and October 2015 -May 2016. Pneumonia was defined
using WHO standard criteria for radiologically confirmed pneumonia. Children with
pneumonia enrolled from January 2014 -April 2016 were compared to children
without pneumonia enrolled from the cross-sectional surveys. Clinical data and
nasopharyngeal (NP) swabs were collected from each child. NP specimens were
cultured for pneumococci, and culture-negative specimens from children with
pneumonia underwent polymerase chain reaction (PCR). RESULTS: Of 778 and 927
children with and without pneumonia, 97.4% and 27.0% were exposed to antibiotics
before swab collection, respectively. Based on culture, pneumococcal colonization
was 45.1% for children with and 84.5% for children without pneumonia (P<0.001);
VT pneumococcal colonization was 18.6% for children with and 23.4% for children
without pneumonia (P = 0.02). The addition of PCR in children with pneumonia
increased overall and VT-pneumococcal colonization to 79.2% and 31.1%,
respectively. In multivariable analysis including PCR results, pneumonia was
associated with VT pneumococcal colonization (adjusted OR: 1.4, 95%CI: 1.10
1.78). CONCLUSION: Vaccine-type pneumococcal colonization remains common among
children with and without pneumonia post-PCV10 introduction in Mozambique. In a
population of children with high antibiotic exposure, the use of PCR for culture
negative NP swabs can improve assessment of pneumococcal colonization and
circulating serotypes.
PMID- 29944696
TI - Targeting vaccinations for the licensed dengue vaccine: Considerations for
serosurvey design.
AB - BACKGROUND: The CYD-TDV vaccine was unusual in that the recommended target
population for vaccination was originally defined not only by age, but also by
transmission setting as defined by seroprevalence. WHO originally recommended
countries consider vaccination against dengue with CYD-TDV vaccine in geographic
settings only where prior infection with any dengue serotype, as measured by
seroprevalence, was >170% in the target age group. Vaccine was not recommended in
settings where seroprevalence was <50%. Test-and-vaccinate strategies suggested
following new analysis by Sanofi will still require age-stratified seroprevalence
surveys to optimise age-group targeting. Here we address considerations for
serosurvey design in the context of vaccination program planning. METHODS: To
explore how the design of seroprevalence surveys affects estimates of
transmission intensity, 100 age-specific seroprevalence surveys were simulated
using a beta-binomial distribution and a simple catalytic model for different
combinations of age-range, survey size, transmission setting, and test
sensitivity/specificity. We then used a Metropolis-Hastings Markov Chain Monte
Carlo algorithm to estimate the force of infection from each simulated dataset.
RESULTS: Sampling from a wide age-range led to more accurate estimates than
merely increasing sample size in a narrow age-range. This finding was consistent
across all transmission settings. The optimum test sensitivity and specificity
given an imperfect test differed by setting with high sensitivity being important
in high transmission settings and high specificity important in low transmission
settings. CONCLUSIONS: When assessing vaccination suitability by seroprevalence
surveys, countries should ensure an appropriate age-range is sampled, considering
epidemiological evidence about the local burden of disease.
PMID- 29944697
TI - Restoration of T Cell function in multi-drug resistant bacterial sepsis after
interleukin-7, anti-PD-L1, and OX-40 administration.
AB - BACKGROUND: Multidrug resistant (MDR) bacterial pathogens are a serious problem
of increasing importance facing the medical community. MDR bacteria typically
infect the most immunologically vulnerable: patients in intensive care units,
patients with extensive comorbidities, oncology patients, hemodialysis patients,
and other immune suppressed individuals are likely to fall victim to these
pathogens. One promising novel approach to treatment of MDR bacteria is immuno
adjuvant therapy to boost patient immunity. Success with this strategy would have
the major benefit of providing protection against a number of MDR pathogens.
OBJECTIVES: This study had two main objectives. First, immunophenotyping of
peripheral blood mononuclear cells from patients with sepsis associated with MDR
bacteria was performed to examine for findings indicative of immunosuppression.
Second, the ability of three immuno-adjuvants with distinct mechanisms of action
to reverse CD4 and CD8 T cell dysfunction, a pathophysiological hallmark of
sepsis, was evaluated. RESULTS: Septic patients with MDR bacteria had increased
expression of the inhibitory receptor PD-1 and its ligand PD-L1 and decreased
monocyte HLA-DR expression compared to non-septic patients. All three immuno
adjuvants, IL-7, anti-PD-L1, and OX-40L, increased T cell production of IFN-gamma
in a subset of septic patients with MDR bacteria: IL-7 was most efficacious.
There was a strong trend toward increased mortality in patients whose T cells
failed to increase IFN-gamma production in response to the three treatments.
CONCLUSION: Immuno-adjuvant therapy reversed T cell dysfunction, a key
pathophysiological mechanism in septic patients with MDR bacteria.
PMID- 29944698
TI - Auditory traits of "own voice".
AB - People perceive their recorded voice differently from their actively spoken
voice. The uncanny valley theory proposes that as an object approaches humanlike
characteristics, there is an increase in the sense of familiarity; however,
eventually a point is reached where the object becomes strangely similar and
makes us feel uneasy. The feeling of discomfort experienced when people hear
their recorded voice may correspond to the floor of the proposed uncanny valley.
To overcome the feeling of eeriness of own-voice recordings, previous studies
have suggested equalization of the recorded voice with various types of filters,
such as step, bandpass, and low-pass, yet the effectiveness of these filters has
not been evaluated. To address this, the aim of experiment 1 was to identify what
type of voice recording was the most representative of one's own voice. The voice
recordings were presented in five different conditions: unadjusted recorded
voice, step filtered voice, bandpass filtered voice, low-pass filtered voice, and
a voice for which the participants freely adjusted the parameters. We found large
individual differences in the most representative own-voice filter. In order to
consider roles of sense of agency, experiment 2 investigated if lip-synching
would influence the rating of own voice. The result suggested lip-synching did
not affect own voice ratings. In experiment 3, based on the assumption that the
voices used in previous experiments corresponded to continuous representations of
non-own voice to own voice, the existence of an uncanny valley was examined.
Familiarity, eeriness, and the sense of own voice were rated. The result did not
support the existence of an uncanny valley. Taken together, the experiments led
us to the following conclusions: there is no general filter that can represent
own voice for everyone, sense of agency has no effect on own voice rating, and
the uncanny valley does not exist for own voice, specifically.
PMID- 29944699
TI - Potential predictive factors for successful referral from specialist mental
health services to less intensive treatment: A concept mapping study.
AB - Referring patients from specialist mental-health services (provided by multiple
healthcare service providers and aimed at relieving symptoms of mental illness)
to less intensive care (provided by a nurse or psychologist in cooperation with a
general practitioner and aimed at improving quality of life) is feasible from the
perspective of patients, service providers, and mental-health services. However,
it is unclear which patients are most suitable for referral to less intensive
care. In this study, we used concept mapping to identify factors that might
determine whether a referral from specialist mental services to less intensive
care might be successful. Participants (N = 34) were recruited from different
parts of the Netherlands and included general practitioners, peer workers,
community mental-health nurses, and social workers from several services who were
based in different neighborhoods. The participants generated 54 statements (31
after clean-up), which were sorted into five clusters and rated on their expected
ability to predict successful referral. Ordered from highest to lowest on
expected predictive value, the clusters of factors were: Patient characteristics,
patients' informal support system, patients' social situation, organization of
services, and service provider related factors. The ordering was the same for all
of the service providers, except that general practitioners expected the
organization of services to be the most predictive. The ordering of the clusters
is mostly consistent with existing knowledge about recovery during mental
healthcare. In order to further improve the number of successful referrals from
specialist mental-health services to less intensive care, a prospective
prediction study is needed.
PMID- 29944700
TI - Long-latency suppression of auditory and somatosensory change-related cortical
responses.
AB - Sensory suppression is a mechanism that attenuates selective information. As for
long-latency suppression in auditory and somatosensory systems, paired-pulse
suppression, observed as 2 identical stimuli spaced by approximately 500 ms, is
widely known, though its mechanism remains to be elucidated. In the present
study, we investigated the relationship between auditory and somatosensory long
latency suppression of change-related cortical responses using
magnetoencephalography. Somatosensory change-related responses were evoked by an
abrupt increase in stimulus strength in a train of current-constant square wave
pulses at 100 Hz to the left median nerve at the wrist. Furthermore, auditory
change-related responses were elicited by an increase in sound pressure by 15 dB
in a continuous sound composed of a train of 25-ms pure tones. Binaural
stimulation was used in Experiment 1, while monaural stimulation was used in
Experiment 2. For both somatosensory and auditory stimuli, the conditioning and
test stimuli were identical, and inserted at 2400 and 3000 ms, respectively. The
results showed clear suppression of the test response in the bilateral
parisylvian region, but not in the postcentral gyrus of the contralateral
hemisphere in the somatosensory system. Similarly, the test response in the
bilateral supratemporal plane (N100m) was suppressed in the auditory system.
Furthermore, there was a significant correlation between suppression of right
N100m and right parisylvian activity, suggesting that similar mechanisms are
involved in both. Finally, a high test-retest reliability for suppression was
seen with both modalities. Suppression revealed in the present study is
considered to reflect sensory inhibition ability in individual subjects.
PMID- 29944701
TI - Tuberculosis in people newly diagnosed with HIV at a large HIV care and treatment
center in Northwest Cameroon: Burden, comparative screening and diagnostic
yields, and patient outcomes.
AB - BACKGROUND: Diagnosis of tuberculosis in people living with HIV is challenging
due to non-specific clinical presentations and inadequately sensitive diagnostic
tests. The WHO recommends screening using a clinical algorithm followed by rapid
diagnosis using the Xpert MTB/RIF assay, and more information is needed to
evaluate these recommendations in different settings. METHODS: From August 2012
to September 2013, consecutive adults newly diagnosed with HIV in Bamenda,
Cameroon, were screened for TB regardless of symptoms by smear microscopy and
culture; the Xpert MTB/RIF assay was performed retrospectively. Time to treatment
and patient outcomes were obtained from routine registers. RESULTS: Among 1,149
people enrolled, 940 (82%) produced sputum for lab testing; of these, 68% were
women, the median age was 35 years (IQR, 28-42 years), the median CD4 count was
291cells/MUL (IQR, 116-496 cells/MUL), and 86% had one or more of current cough,
fever, night sweats, or weight loss. In total, 131 people (14%, 95% CI, 12-16%)
had sputum culture-positive TB. The WHO symptom screening algorithm had a
sensitivity of 92% (95%CI, 86-96%) and specificity of 15% (95%CI, 12-17%) in this
population. Compared to TB culture, the sensitivity of direct smear microscopy
was 25% (95% CI, 18-34%), and the sensitivity of Xpert was 68% (95% CI, 58-76);
the sensitivity of both was higher for people reporting more symptoms. Only one
of 69 people with smear-negative/culture-positive TB was started on TB treatment
prior to culture positivity. Of 71 people with bacteriologically-confirmed TB and
known outcome after 6 months, 13 (17%) had died, including 11 people with smear
negative TB and 6 people with both smear and Xpert-negative TB. CONCLUSIONS: Use
of the most sensitive rapid diagnostic test available is critical in people newly
diagnosed with HIV in this setting to maximize the detection of bacteriologically
confirmed TB. However, this intervention is not sufficient alone and should be
combined with more comprehensive clinical diagnosis of TB to improve outcomes.
PMID- 29944702
TI - Acuity and colour vision changes post intravitreal dexamethasone implant
injection in patients with diabetic macular oedema.
AB - PURPOSE: To evaluate changes in colour vision following intravitreal injection of
Dexamethasone implant (Ozurdex) in patients with diabetic macular oedema (DMO).
Both red-green (RG) and yellow-blue (YB) chromatic sensitivity were assessed
using the Colour Assessment & Diagnosis (CAD) test which isolates the use of
colour signals and provides age-corrected, statistical limits for normal
trichromats. To determine whether colour changes and visual acuity (VA) post
treatment relate to central sub-field retinal thickness (CST). METHODS: Fourteen
patients with DMO who were undergoing treatment with Ozurdex were recruited for
this study. RG and YB colour thresholds were measured using the CAD test, best
corrected visual acuity was assessed using the ETDRS chart and CST was measured
using spectral domain optical coherence tomography (SD-OCT). All tests were
performed monocularly at baseline and 24 weeks post injection. RESULTS: All
patients (n = 14 eyes), had significant loss of RG and YB chromatic sensitivity
at baseline (p<0.05). The mean age was 56 +/- 9.5 years. The age specific,
monocular, upper normal limits for a 56 year old subject are 2.66 for RG and 2.85
for YB. In this study, the measured, pre injection thresholds (mean+/-SD) were
22.6 +/- 11.3 for RG and 16.2 +/- 3.76 for YB. There was significant improvement
in RG threshold post injection (i.e., 19.2 +/- 10.8 (p<0.05)). No significant
changes were found in the YB thresholds with corresponding mean and range values
of: 15.8 +/- 4.6 (p = 0.23). CST pre-treatment was 542 +/-135 MUm. After
treatment and by week 24 the CST values decreased to 435 +/-127 MUm. CONCLUSIONS:
RG colour thresholds provide a sensitive measure of functional change in diabetic
subjects with macular oedema. The YB system is damaged severely in the DMO
patients studied and shows little or no recovery post treatment. The improvement
in VA and particularly in RG colour vision correlate well with the measured
decrease in CST. The results suggest that the improvement in the RG chromatic
sensitivity can provide a useful biomarker for monitoring the efficacy of
treatment in DMO.
PMID- 29944703
TI - Association of serum BDNF levels and the BDNF Val66Met polymorphism with the
sleep pattern in healthy young adults.
AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is widely expressed in the
brain and plays an important role in neuronal maintenance, plasticity, and
neurogenesis. Prior studies have found that decreased serum BDNF levels are
associated with perceived stress, depression, or sleep disturbances in humans.
STUDY OBJECTIVES: To elucidate whether the serum BDNF levels and BDNF genotype
were associated with the sleep pattern in healthy young adults. METHODS: The
study group consisted of 79 healthy paid volunteers (45 men, 34 women) aged 20 to
29 years. Serum BDNF levels were measured with an enzyme-linked immunosorbent
assay, and a single-nucleotide polymorphism (Val66Met) in the BDNF gene was
assessed with a TaqMan assay. Details of the sleep pattern were obtained from 1
week sleep/wake records. RESULTS: Serum BDNF levels were significantly associated
with sleep parameters on weekends, whereas no such association was found on
weekdays. On weekends, longer total sleep time and time in bed, and later mid
sleep time were associated with lower serum BDNF levels. The difference between
mid-sleep time on weekdays and that on weekends, otherwise known as social
jetlag, was negatively associated with serum BDNF levels. Met/Met homozygotes of
the BDNF Val66Met polymorphism had significantly longer time in bed on weekends
than Val/Val homozygotes. Heterozygotes did not differ from Val/Val homozygotes.
CONCLUSIONS: We first found that serum BDNF levels and the BDNF Val66Met
polymorphism in healthy young adults were associated with the sleep pattern on
weekends but not with that on weekdays, suggesting that the systems involved in
BDNF control may be linked to endogenous sleep characteristics rather than the
socially constrained sleep schedule in healthy young adults.
PMID- 29944705
TI - Correction: In Vitro Evolution and Affinity-Maturation with Coliphage Qbeta
Display.
AB - [This corrects the article DOI: 10.1371/journal.pone.0113069.].
PMID- 29944704
TI - The effects of the Nepal community forestry program on biodiversity conservation
and carbon storage.
AB - Approximately 15.5% of global forest is controlled by ~1 billion local people and
the area under community control is increasing. However, there is limited
empirical evidence as to whether community control is effective in providing
critical global ecosystem services, such as biodiversity conservation and carbon
storage. We assess the effectiveness of one example of community-controlled
forest, Nepal's Community Forestry Program (CFP), at providing biodiversity
conservation and carbon storage. Using data from 620 randomly selected CFP and
non-CFP forest plots, we apply a robust matching method based on covariates to
estimate whether CFPs are associated with greater biodiversity conservation or
carbon storage. Our results reveal a significant positive effect of CFP on
biodiversity, which is robust against the influence of unobserved covariates. Our
results also suggest a significant negative effect of the CFP on aboveground tree
and sapling carbon (AGC) at the national scale (-15.11 Mg C ha-1). However, the
CFP has a mixed effect on carbon across geographic and topographic regions and in
forests with different canopy covers. Though there were no significant effects of
the CFP on AGC at lower altitudes, in the Terai or hill regions, and under closed
canopies, there were positive effects in open canopies (25.84 Mg C ha-1) at lower
slopes (25.51 Mg C ha-1) and negative effects at higher altitudes (-22.81 Mg C ha
1) and higher slopes (-17.72 Mg C ha-1). Our sensitivity analysis revealed that
the positive effects are robust to unobserved covariates, which is not true for
the negative results. In aggregate, our results demonstrate that CFP can be an
effective forest management strategy to contribute to global ecosystem services
such as biodiversity, and to a lesser extent carbon.
PMID- 29944706
TI - Nonadherence to daily self-weighing and activity tracking is associated with
weight fluctuations among African American breast cancer survivors.
AB - INTRODUCTION: Daily self-weighing (DSW) and daily activity tracking (DAT) are
useful strategies for preventing weight gain among African American breast cancer
survivors. However, self-monitoring behaviors vary over time, increasing risk of
weight gain. This study explored the association of nonadherence to DSW and DAT
with corresponding weight fluctuations among African American breast cancer
survivors. METHODS: Using data from a 6-month randomized controlled trial, we
conducted a secondary data analysis among women randomized into a DSW group (n =
13) and a DSW+DAT group (n = 11). DSW and DAT were captured from wireless scale
and activity tracker data. Nonadherence to DSW was defined as one or more days
without a weight measurement, and nonadherence to DAT was defined as one or more
days without activity tracking. Generalized estimating equations were used to
examine weight fluctuations in relation to nonadherence to DSW and DAT. Data
analysis occurred from September 2016-April 2017. RESULTS: Over the 6-month study
period, women provided 119.2 +/- 46.0 weight measurements and 121.9 +/- 53.2 days
of physical activity tracking. Nonadherence to DSW was associated with weight
fluctuations. For every 1-day increase in nonadherence to DSW, weight increased
by 0.031 kg (95% CI: 0.012, 0.050; p<0.01). Additionally, during periods of DSW
and DAT weight decreased by 0.028 kg (95% CI: -0.042, -0.014; p<0.001) and 0.017
kg (95% CI: -0.030; -0.004) respectively. CONCLUSIONS: Our findings suggest that
nonadherence to DSW was associated with weight gain among breast cancer
survivors. Weight loss was enhanced during periods of DSW and DAT.
PMID- 29944707
TI - Ambulatory function in spinal muscular atrophy: Age-related patterns of
progression.
AB - Individuals with spinal muscular atrophy (SMA) type 3 are able to walk but they
have weakness, gait impairments and fatigue. Our primary study objective was to
examine longitudinal changes in the six-minute walk test (6MWT) and to evaluate
whether age and SMA type 3 subtype are associated with decline in ambulatory
function. Data from three prospective natural history studies were used. Seventy
three participants who performed the 6MWT more than once, at least 6 months
apart, were included; follow-up ranged from 0.5-9 years. Only data from patients
who completed the 6MWT were included. The mean age of the participants was 13.5
years (range 2.6-49.1), with 52 having disease onset before age 3 years (type
3A). At baseline, type 3A participants walked a shorter distance on average
(257.1 m) than type 3B participants (390.2 m) (difference = 133.1 m, 95%
confidence interval [CI] 71.8-194.3, p < 0.001). Distance walked was weakly
associated with age (r = 0.25, p = 0.04). Linear mixed effects models were used
to estimate the mean annual rate of change. The overall mean rate of change was
7.8 m/year (95% CI -13.6 --2.0, p = 0.009) and this did not differ by subtype
(type 3A: -8.5 m/year, type 3B: -6.6 m/year, p = 0.78), but it did differ by age
group (< 6: 9.8 m/year; 6-10: -7.9 m/year; 11-19: -20.8 m/year; >= 20: -9.7
m/year; p = 0.005). Our results showed an overall decline on the 6MWT over time,
but different trajectories were observed depending on age. Young ambulant SMA
patients gain function but in adolescence, patients lose function. Future
clinical trials in ambulant SMA patients should consider in their design the
different trajectories of ambulatory function over time, based on age.
PMID- 29944708
TI - Self-triage for acute primary care via a smartphone application: Practical, safe
and efficient?
AB - BACKGROUND: Since the start of out-of-hours (OOH) primary care clinics, the
number of patient consultations has been increasing. Triage plays an important
role in patient selection for a consultation, and in providing reassurance and
self-management advice. OBJECTIVE: We aimed to investigate whether the smartphone
application "Should I see a doctor?" (in Dutch:"moet ik naar de dokter?") could
guide patients in appropriate consultation at OOH clinics by focusing on four
topics: 1) app usage, 2) user satisfaction, 3) whether the app provides the
correct advice, and 4) whether users intend to follow the advice. DESIGN AND
SETTING: A prospective, cross-sectional study amongst app users in a routine
primary care setting. METHODS: The app is a self-triage tool for acute primary
care. A built-in questionnaire asked users about the app's clarity, their
satisfaction and whether they intended to follow the app's advice (n = 4456). A
convenience sample of users was phoned by a triage nurse (reference standard) to
evaluate whether the app's advice corresponded with the outcome of the triage
call (n = 126). Suggestions of phoned participants were listed. RESULTS: The app
was used by patients of all ages, also by parents for their children, and mostly
for abdominal pain, skin disorders and cough. 58% of users received the advice to
contact the clinic, 34% a self-care advice and 8% to wait-and-see. 65% of users
intended to follow the app's advice. The app was rated as 'neutral' to 'very
clear' by 87%, and 89% were 'neutral' to 'very satisfied'. In 81% of participants
the app's advice corresponded to the triage call outcome, with sensitivity,
specificity, positive- and negative predictive values of 84%, 74%, 88% and 67%,
respectively. CONCLUSION: The app "Should I see a doctor?" could be a valuable
tool to guide patients in contacting the OOH primary care clinic for acute care.
To further improve the app's safety and efficiency, triaging multiple symptoms
should be facilitated, and more information should be provided to patients
receiving a wait-and-see advice.
PMID- 29944709
TI - Intermediate levels of vaccination coverage may minimize seasonal influenza
outbreaks.
AB - For most pathogens, vaccination reduces the spread of the infection and total
number of cases; thus, public policy usually advocates maximizing vaccination
coverage. We use simple mathematical models to explore how this may be different
for pathogens, such as influenza, which exhibit strain variation. Our models
predict that the total number of seasonal influenza infections is minimized at an
intermediate (rather than maximal) level of vaccination, and, somewhat counter
intuitively, further increasing the level of the vaccination coverage may lead to
higher number of influenza infections and be detrimental to the public interest.
This arises due to the combined effects of: competition between multiple co
circulating strains; limited breadth of protection afforded by the vaccine; and
short-term strain-transcending immunity following natural infection. The study
highlights the need for better quantification of the components of vaccine
efficacy and longevity of strain-transcending cross-immunity in order to generate
nuanced recommendations for influenza vaccine coverage levels.
PMID- 29944711
TI - How do futsal players of different categories play during official matches? A
tactical approach to players' organization on the court from positional data.
AB - The purpose of this study was to analyze futsal players' organization on the
court in different categories while attacking and defending, in interception and
shot to goal situations. We obtained the trajectories of 89 players from the
under-15 category, 102 players from the under-18 category, and 110 professional
players, during official matches. The spread, surface area, and Euclidian
distances between the teams' centroids were measured to represent the
distribution of the futsal players on the court. The variables were analyzed
during each offensive and defensive sequence, and during situations of shots to
goal and interceptions, with and without the outfield goalkeeper player
participation. While the players were attacking, all categories presented greater
spread and surface area, compared to values when players were defending (P <
0.01). Among the categories, the results showed lower spread and area values for
the younger players (P < 0.01). The results of spread, surface area, and
distances between the teams' centroids showed different forms of organization for
each of the categories in specific situations of shots to goal and interceptions.
The study provided insights that allow coaches to better plan suitable tactical
training according to the requirements of each category.
PMID- 29944710
TI - Nonaplex PCR using Cliffhanger primers to identify diarrhoeagenic Escherichia
coli from crude lysates of human faecal samples.
AB - Sensitive, probe-based detection of multiple DNA targets is limited by the
competitive reannealing of the antiparallel duplex DNA helix with the
complementary DNA strand. To address this, we developed Cliffhanger primers,
which create single-stranded DNA overhangs on PCR amplicons while simultaneously
increasing the multiplex PCR efficacy and allowing PCR amplification using crude
lysates of human faecal samples. A multiplex PCR that targeted eight genes from
diarrhoeagenic Escherichia coli plus an internal control was performed and
compared to a routine method that consisted of culture followed by multiplex PCR
with fragment length separation. A total of 2515 clinical faecal samples from
patients with diarrhoea were tested using both methods, and there was a
significant increase in clinical sensitivity and negative predictive value with
the Cliffhanger method for seven out of eight genes. All Cliffhanger-only
positive samples were confirmed by Sanger sequencing of the PCR amplicon.
Notably, the Cliffhanger method reduced the total sample turn-around time in the
laboratory from 20 hours to 6 hours. Hence, use of Cliffhanger primers increased
assay robustness, decreased turn-around time and increased PCR efficacy. This
increased the overall clinical sensitivity without the loss of specificity for a
heavily multiplexed PCR assay.
PMID- 29944712
TI - Effectiveness of a multi-facetted blended eHealth intervention during intake
supporting patients and clinicians in Shared Decision Making: A cluster
randomised controlled trial in a specialist mental health outpatient setting.
AB - OBJECTIVE: To investigate the effectiveness of a multi-facetted blended eHealth
intervention, called SDM-Digital Intake (SDM-DI), in which patients and
clinicians are supported in Shared Decision Making during the intake process.
METHODS: The study is a two-arm matched-paired cluster Randomised Controlled
Trial in a specialist mental health outpatient setting with two conditions: SDM
DI and Intake As Usual (IAU). Four intake teams were allocated to each arm. All
patients who followed an intake, were asked to participate if they were capable
to complete questionnaires. Decisional Conflict (DC), referring to patients'
engagement and satisfaction with clinical decisions, was the primary outcome.
Secondary outcomes were patient participation, applying Shared Decision Making
(SDM), working alliance, treatment adherence and symptom severity. Effects were
measured at two weeks (T1) and two months (T2) after intake. Multilevel
regression and intention-to-treat analyses were used. Additionally, the influence
of subgroups and intervention adherence on DC were explored. RESULTS: At T1, 200
patients participated (47% intervention, 53% control), and at T2 175 patients
(47% intervention, 53% control). At T1 and T2, no differences were found between
conditions on DC. Subgroup analyses showed that effects of SDM-DI on DC were not
modified by primary diagnoses mood, anxiety and personality disorders. Compared
to IAU, at T2, patients reported positive effects of SDM-DI on SDM (beta 7.553, p
= 0.038, 95%CI:0.403-14.703, d = 0.32) and reduction of symptoms (beta -7.276, p
= 0.0497, 95%CI:-14.544--0.008, d = -0.43). No effects were found on patient
participation, working alliance and treatment adherence. Exploratory analyses
demonstrated that if SDM was applied well, patients reported less DC (beta =
0.457, p = 0.000, 95%CI:-0.518--0.396, d = -1.31), which was associated with
better treatment outcomes. CONCLUSION: Although, this trial fails to demonstrate
that SDM-DI by itself is sufficient to reduce DC, the results are encouraging for
further efforts in improving and implementing the SDM intervention.
PMID- 29944713
TI - Multiple insecticide resistance in Culex quinquefasciatus populations from
Guadeloupe (French West Indies) and associated mechanisms.
AB - West Nile (WN) virus has been detected in Guadeloupe since 2002. Even if no WN
human cases have been detected so far, mosquitoes from Culex genus especially
Culex quinquefasciatus are recognized as potential WN vectors in Guadeloupe. To
evaluate the impact of local vector control activities on this mosquito species
we assessed the resistance levels of Cx. quinquefasciatus populations from three
different sites from Guadeloupe (Abymes, Saint Francois and Gourbeyre) to
malathion, temephos and deltamethrin. In addition, the frequencies of the L1014F
kdr and the G119S ace-1 mutations were established in Cx. quinquefasciatus
populations, as well as the constitutive expressions of five cytochrome P450
genes. Mosquito populations tested displayed high resistance to deltamethrin,
moderate resistance to malathion (Abymes, Gourbeyre) and low resistance to
temephos (Abymes et Gourbeyre). Molecular analyses revealed high frequencies of
both L1014F kdr and G119S ace-1 mutations in Cx. quinquefasciatus populations, as
well as overexpression of cytochrome P450 genes CYP9J45, CYP9J40 and CYP6AA7.
Finally, deltamethrin resistance and knock-down rates were strongly correlated
with the frequency of the resistant kdr and ace-1 alleles, as well as with
CYP9J40 overexpression. These results should be taken into account to refine the
current vector control strategies to prevent the appearance of Cx.
quinquefasciatus-borne diseases in Guadeloupe.
PMID- 29944714
TI - Susceptibility of epithelial cells cultured from different regions of human
cervix to HPV16-induced immortalization.
AB - Persistent infection with high-risk human papillomavirus (HPV) is a major risk
factor for cervical cancer. Greater than 90% of these cancers originate in the
cervical transformation zone (TZ), a narrow region of metaplastic squamous
epithelium that develops at the squamocolumnar junction between the ectocervix
and endocervix. It is unclear why the TZ has high susceptibility to malignant
transformation and few studies have specifically examined cells from this region.
We hypothesized that cells cultured from TZ are more susceptible to cellular
immortalization, an alteration that contributes to malignant development. We
cultured primary epithelial cells from each region of human cervix (ectocervix,
endocervix and TZ) and measured susceptibility to immortalization after
transfection with the complete HPV-16 genome or infection of HPV16 E6/E7
retroviruses. Cells cultured from each cervical region expressed keratin markers
(keratin 14 and 18) that confirmed their region of origin. In contrast to our
prediction, cells from TZ were equally susceptible to immortalization as cells
from ectocervix or endocervix. Thus, increased susceptibility of the TZ to
cervical carcinogenesis is not due to increased frequency of immortalization by
HPV-16. We developed a series of HPV16-immortalized cell lines from ectocervix,
endocervix and TZ that will enable comparisons of how these cells respond to
factors that promote cervical carcinogenesis.
PMID- 29944715
TI - An open source microcontroller based flume for evaluating swimming performance of
larval, juvenile, and adult zebrafish.
AB - Zebrafish are a preferred vertebrate model for delineating genotype-phenotype
relationships. One of the most studied features of zebrafish is their exceptional
swimming ability. By 7 days postfertilization (dpf), zebrafish spend over two
thirds of their time engaged in spontaneous swimming activity and several months
later they are capable of attaining some of the fastest swimming velocities
relative to body length ever recorded in the laboratory. However, laboratory
assembled flumes capable of achieving the slow flow velocities characteristics of
larvae as well as the relatively fast maximal velocities of adults have not been
described in sufficient detail to allow easy replication. Here we describe an
easily assembled, open-source zebrafish-scaled flume for assessing swimming
performance. The flume uses two independent spherical-impeller pumps modulated by
a microcontroller to achieve flow velocities ranging from 1 to 70 cm s-1. The
microcontroller also monitors water temperature and flow velocity and sends these
data to a personal computer for real-time display and storage. Incremental
protocols for assessing maximal swimming speed (Umax) were developed, stored in
custom software, and then uploaded to the microcontroller in order to assess
performance of larval (14, 21, 28 dpf), juvenile (35, 42 dpf), and adult (8, 22
month) zebrafish. The flume had sufficient range and sensitivity to detect
developmental changes in Umax of larvae and juveniles, an 18-24% faster Umax of
adult males vs. females, and a 14-20% age-related reduction in Umax for the
oldest zebrafish. Detailed information is provided to assemble and operate this
low-cost, versatile, and reliable tool for assessing zebrafish swimming
performance.
PMID- 29944716
TI - Biocompatibility and antibacterial properties of zirconium nitride coating on
titanium abutments: An in vitro study.
AB - Improving soft tissue attachment and reducing bacterial colonization on titanium
abutments are key factors for the long-term maintenance of healthy soft and hard
peri-implant tissues. This in vitro study was conducted to compare the
biocompatibility and antibacterial activity of four different surfaces: uncoated
Ti6Al4V, anodized, and coated with titanium nitride or zirconium nitride. Surface
topography was investigated with a high-resolution system for measuring surface
finishes. Human gingival fibroblast (HGF) adhesion and proliferation were
examined using MTT assay, Scanning Electron Microscopy (SEM) imaging,
immunofluorescence analysis and real-time PCR for selected target genes. The
hemolysis and AMES tests were performed to assess the chemical compounds' blood
compatibility and mutagenic potential, respectively. Antibacterial activity was
tested against five bacterial strains isolated from the oral cavity
(Streptococcus salivarius, S. sanguinis, S. mutans, S. sobrinus, S. oralis), and
the percentage of dead bacteria was calculated. Roughness measurements confirmed
a substantial similarity between the surfaces and their compatibility with
clinical applications. MTT assay, SEM analysis and immunofluorescence staining
showed adhesion and proliferation of HGFs cultured on all the examined surfaces.
PCR confirmed that HGFs produced extracellular matrix components efficiently on
all the surfaces. No hemolytic activity was detected, and the AMES test confirmed
the surfaces' clinical safety. For all tested bacterial strains, biofilms grown
on the zirconium nitride surface showed a higher percentage of dead bacteria than
on the other disks. The titanium nitride surface inactivated bacterial biofilms,
too, but to a lesser extent.
PMID- 29944717
TI - Excellent accuracy of ABC/2 volume formula compared to computer-assisted
volumetric analysis of subdural hematomas.
AB - BACKGROUND: Subdural hematoma (SDH) is a common disease associated with high
morbidity, which is becoming more prominent due to the increasing incidence.
Decision for a surgical evacuation is made depending on the clinical appearance
and the volume of SDH, wherefore it is important to have a simple 'bedside'
method to measure and compare the volume of SDH. OBJECTIVE: The aim of the study
was to verify the accuracy of the simplified ABC/2 volumetric formula to
determine a valuable tool for the clinical practice. METHODS: Preoperative CT
scans of 83 patients with SDHs were used for the computer-assisted volumetric
measurement via BrainLab(r) as well as the ABC/2 volumetric measurement. A =
largest length (anterior to posterior) of the SDH; B = maximum width (lateral to
midline) 90 degrees to A; C = maximum height (coronal plane or multiplication of
slices) of the hematoma. These measurements were performed by two independent
clinicians in a blinded fashion. Both volumes were compared by linear regression
analysis of Pearson and Bland-Altman regression analysis. RESULTS: Among 100
SDHs, 53% were under an 47% were over 100cm3 showing a well distribution of the
hematoma sizes. There was an excellent correlation between computer-assisted
volumetric measurement and ABC/2 (R2 = 0.947, p<0.0001) and no undesirable
deviation and trend were detected (p = 0.101; p = 0.777). A 95% tolerance region
of the ratios of both methods was [0.805-1.201]. CONCLUSION: The ABC/2 method is
a simple and fast bedside formula for the measurement of SDH volume in a timely
manner without limited access through simple adaption, which may replace the
computer-assisted volumetric measurement in the clinical and research area.
Reason for the good accuracy seems to be the spherical form of SDH, which has a
similarity to a half ellipsoid.
PMID- 29944718
TI - Agreement between pre-exercise screening questionnaires completed online versus
face-to-face.
AB - OBJECTIVES: To investigate the levels of agreement between self-reported
responses to the Adult Pre-exercise Screening System (APSS) questionnaire using
online versus face-to-face (F2F) modalities. DESIGN: Convenience sample of adults
completing a pre-exercise screening questionnaire using different modalities.
METHODS: Adult volunteers (n = 94) were recruited to complete the APSS using both
online and F2F modalities. Participants were provided a URL link to an online
APSS questionnaire then followed-up the next day in a F2F interview. Objective
health risk factors were also measured. Comparisons between responses were
undertaken using kappa and correlation statistics to determine levels of
agreement. RESULTS: The levels of agreement between online versus F2F responses
for the seven compulsory Stage 1 questions (known diseases and signs and/or
symptoms of disease) were >94% (kappa = 0.644-0.794). Response comparisons for
Stage 2 questions on health risk factors were also generally high (>82%
agreement) but there were larger differences between reported and measured risk
factors in Stage 3. CONCLUSIONS: Levels of agreement between the Stage 1
responses were substantial and support the use of this online option for pre
exercise screening. There were larger differences between self-reported and
objectively measured health risk factors in Stages 2 and 3.
PMID- 29944719
TI - Dopamine and its receptors play a role in the modulation of CCR5 expression in
innate immune cells following exposure to Methamphetamine: Implications to HIV
infection.
AB - The Human Immunodeficiency Virus (HIV) infects cells in the Central Nervous
System (CNS), where the access of antiretrovirals and antibodies that can kill
the virus may be challenging. As a result of the early HIV entry in the brain,
infected individuals develop inflammation and neurological deficits at various
levels, which are aggravated by drugs of abuse. In the non-human primate model of
HIV, we have previously shown that drugs of abuse such as Methamphetamine (Meth)
increase brain viral load in correlation with a higher number of CCR5-expressing
myeloid cells. CCR5 is a chemokine receptor that may be involved in increasing
inflammation, but also, it is a co-receptor for viral entry into target cells.
CCR5-expressing myeloid cells are the main targets of HIV in the CNS. Thus, the
identification of factors and mechanisms that impact the expression of CCR5 in
the brain is critical, as changes in CCR5 levels may affect the infection in the
brain. Using a well-characterized in vitro system, with the THP1 human macrophage
cell line, we have investigated the hypothesis that the expression of CCR5 is
acutely affected by Meth, and examined pathways by which this effect could
happen. We found that Meth plays a direct role by regulating the abundance and
nuclear translocation of transcription factors with binding sites in the CCR5
promoter. However, we found that the main factor that modifies the CCR5 gene
promoter at the epigenetic level towards transcription is Dopamine (DA), a
neurotransmitter that is produced primarily in brain regions that are rich in
dopaminergic neurons. In THP1 cells, the effect of DA on innate immune CCR5
transcription was mediated by DA receptors (DRDs), mainly DRD4. We also
identified a role for DRD1 in suppressing CCR5 expression in this myeloid cell
system, with potential implications for therapy. The effect of DA on innate
immune CCR5 expression was also detectable on the cell surface during acute time
points, using low doses. In addition, HIV Tat acted by enhancing the surface
expression of CCR5, in spite of its poor effect on transcription. Overall, our
data suggests that the exposure of myeloid cells to Meth in the context of
presence of HIV peptides such as Tat, may affect the number of HIV targets by
modulating CCR5 expression, through a combination of DA-dependent and-independent
mechanisms. Other drugs that increase DA may affect similar mechanisms. The
implications of these epigenetic and translational mechanisms in enhancing HIV
infection in the brain and elsewhere are demonstrated.
PMID- 29944720
TI - Correction: Chronological reassessment of the Middle to Upper Paleolithic
transition and Early Upper Paleolithic cultures in Cantabrian Spain.
AB - [This corrects the article DOI: 10.1371/journal.pone.0194708.].
PMID- 29944721
TI - B cells are capable of independently eliciting rapid reactivation of
encephalitogenic CD4 T cells in a murine model of multiple sclerosis.
AB - Recent success with B cell depletion therapies has revitalized efforts to
understand the pathogenic role of B cells in Multiple Sclerosis (MS). Using the
adoptive transfer system of experimental autoimmune encephalomyelitis (EAE), a
murine model of MS, we have previously shown that mice in which B cells are the
only MHCII-expressing antigen presenting cell (APC) are susceptible to EAE.
However, a reproducible delay in the day of onset of disease driven by exclusive
B cell antigen presentation suggests that B cells require optimal conditions to
function as APCs in EAE. In this study, we utilize an in vivo genetic system to
conditionally and temporally regulate expression of MHCII to test the hypothesis
that B cell APCs mediate attenuated and delayed neuroinflammatory T cell
responses during EAE. Remarkably, induction of MHCII on B cells following the
transfer of encephalitogenic CD4 T cells induced a rapid and robust form of EAE,
while no change in the time to disease onset occurred for recipient mice in which
MHCII is induced on a normal complement of APC subsets. Changes in CD4 T cell
activation over time did not account for more rapid onset of EAE symptoms in this
new B cell-mediated EAE model. Our system represents a novel model to study how
the timing of pathogenic cognate interactions between lymphocytes facilitates the
development of autoimmune attacks within the CNS.
PMID- 29944722
TI - Correction: Active Sites of Reduced Epidermal Fluorescence1 (REF1) Isoforms
Contain Amino Acid Substitutions That Are Different between Monocots and Dicots.
AB - [This corrects the article DOI: 10.1371/journal.pone.0165867.].
PMID- 29944723
TI - Correction: Physiochemical characterization and cytotoxicity evaluation of
mercury-based formulation for the development of anticancer therapeuticals.
AB - [This corrects the article DOI: 10.1371/journal.pone.0195800.].
PMID- 29944724
TI - A whole-genome transcriptome analysis of articular chondrocytes in secondary
osteoarthritis of the hip.
AB - OBJECTIVE: To date, exhaustive gene expression analyses of chondrocytes in hip
osteoarthritis (OA) have yielded specific gene expression patterns. No study has
reported on the exhaustive transcriptome of secondary hip OA based on acetabular
dysplasia in a Japanese population, while previous reports have focused on
primary or idiopathic hip OA in Caucasian populations. This study aims to search
for specific gene expression patterns of secondary hip OA chondrocytes by
transcriptome analysis. DESIGN: Human articular cartilage was obtained from
femoral heads following hemiarthroplasty for femoral neck fracture (N = 8; non
OA) and total hip arthroplasty for secondary hip OA (N = 12). Total RNA was
extracted from the articular cartilage and submitted for microarray analysis. The
obtained data were used to perform gene expression analysis, GO enrichment
analysis and pathway analysis and were compared with data from primary hip OA in
Caucasian populations in the literature. RESULTS: We identified 888 upregulated
(fold change: FC >= 2) and 732 downregulated (FC <= 0.5) genes in hip OA versus
non-OA chondrocytes, respectively. Only 10% of upregulated genes were common
between the secondary and primary OA. The newly found genes prominently
overexpressed in the secondary hip OA chondrocytes were DPT, IGFBP7, and KLF2.
Pathway analysis revealed extracellular matrix (ECM)-receptor interaction as an
OA-related pathway, which was similar to previous reports in primary hip OA.
CONCLUSIONS: This is the first study to report the genome-wide transcriptome of
secondary hip OA chondrocytes and demonstrates new potential OA-related genes.
Gene expression patterns were different between secondary and primary hip OA,
although the results of pathway and functional analysis were similar.
PMID- 29944725
TI - Correction: Global migration of clinical research during the era of trial
registration.
AB - [This corrects the article DOI: 10.1371/journal.pone.0192413.].
PMID- 29944726
TI - In vitro cytotoxicity of superheated steam hydrolyzed oligo((R)-3-hydroxybutyrate
co-(R)-3-hydroxyhexanoate) and characteristics of its blend with poly(L-lactic
acid) for biomaterial applications.
AB - In order to clarify the in vitro cytotoxicity effect of superheated steam (SHS)
treated poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) (PHBHHx) for
biomaterial applications, SHS-treated PHBHHx oligoester samples: P(HB-co-6%-HHx)
and P(HB-co-11%-HHx) with low and high percentages of unsaturated chain ends were
evaluated for their cytotoxicity effects toward the growth of mouse fibroblast
cell line NIH 3T3. From the results obtained after 24 and 48 h of the growth
test, the SHS-treated PHBHHx oligoesters were found to be nontoxic to the growth
of mouse fibroblast NIH 3T3 cell line with cell viability percentages of more
than 95%. In order to serve as a potential resorbable medical suture, PHBHHx
oligoesters were blended with poly(L-lactic acid) (PLLA) with a weight ratio of
PHBHHx oligoester/PLLA = 20:80 (wt/wt) to improve mechanical properties of PHBHHx
oligoesters. The PHBHHx oligoesters/PLLA blend films were evaluated for their
thermal, mechanical, and surface wetting properties. Thermal properties of the
blend films suggested a good compatibility between PHBHHx oligoesters and PLLA
components. Mechanical properties of the blend films were determined to be close
enough to a desirable strength range of medical sutures. Moreover, contact angle
range of 65 < theta < 70 degrees for the blend samples could provide desirable
cell adhesion when used as biomaterials. Therefore, the blend of SHS-treated
PHBHHx oligoesters and PLLA would be an ideal choice to be used as biomedical
materials.
PMID- 29944727
TI - Correction: Prospective comparison among transient elastography, supersonic shear
imaging, and ARFI imaging for predicting fibrosis in nonalcoholic fatty liver
disease.
AB - [This corrects the article DOI: 10.1371/journal.pone.0188321.].
PMID- 29944728
TI - Impact of operational factors on HPV positivity rates in an HPV-based screening
study in Colombia.
AB - OBJECTIVE: To assess the effect of operational factors on the positivity rates of
three HPV assays. METHODS: Within the cross-sectional ESTAMPA study, women aged
30-64 years were recruited at healthcare centers from Soacha, Colombia, during
2012-2015. Cervical samples were collected for cotesting with Hybrid Capture 2
(HC2; Qiagen, Gaithersburg, MD, USA), and either Aptima (Hologic, Marlborough,
MA, USA) or Cobas 4800 (Roche Diagnostics, Indianapolis, IN, USA). The effect of
operational factors on assay performance was assessed using adjusted positivity
rates obtained from logistic regression models. RESULTS: There were 4168 women
included. For samples collected in assay-specific medium, positivity rate
differences were associated with the expertise of the nurse collecting the sample
(P=0.014 HC2; P=0.091 Aptima) and if sample collection occurred after an initial
cytology (P=0.025 HC2; P=0.033 Aptima). If PreservCyt medium (Hologic) was used,
HC2 positivity differences were observed depending on the time between sample
collection and processing (P=0.026) and on the laboratory technician processing
the samples (P=0.003). No differences were observed for PreservCyt samples
processed with Aptima or Cobas. CONCLUSION: Nurse expertise, collection of
previous cytology, processing time, and laboratory technician could influence HPV
assay performance. Suitable quality assurance protocols for HPV-based screening
programs are required. ClinicalTrials.gov: NCT01881659.
PMID- 29944729
TI - Systematic review and meta-analysis of complementary treatments for women with
symptomatic endometriosis.
AB - BACKGROUND: Despite advances in treatments for endometriosis, some symptoms
persist owing to the chronic inflammation observed in this disease. OBJECTIVE: To
identify resources, methods, and/or complementary treatments to alleviate the
pain symptoms of endometriosis, and to identify adverse effects of treatments.
SEARCH STRATEGY: Lilacs, Scielo, PEDro, Scopus, Pubmed, CENTRAL Cochrane, Science
Direct, and Google Scholar were searched for studies published in Portuguese,
English, and Spanish to July 31, 2017, using the terms "physical therapy" OR
"complementary treatment" AND "endometriosis". SELECTION CRITERIA: Randomized
controlled trials relating to complementary pelvic pain treatment and adverse
effects. DATA COLLECTION AND ANALYSIS: Eight studies were identified; two studies
were included in the meta-analysis. MAIN RESULTS: The complementary interventions
studied were acupuncture, exercise, electrotherapy, and yoga. All were
inconclusive in affirming benefit, but demonstrated a positive trend in the
treatment of symptoms of endometriosis. Meta-analysis of acupuncture showed a
significant benefit in pain reduction as compared with placebo (P=0.007).
CONCLUSIONS: Numerous complementary treatments have been used to alleviate the
symptoms of endometriosis, but only acupuncture has demonstrated a significant
improvement in outcomes. Nevertheless, other approaches demonstrated positive
trends toward improving symptoms; this should encourage investigators to design
controlled studies to support their applicability.
PMID- 29944730
TI - Beyond body size: consistent decrease of traits within orthopteran assemblages
with elevation.
AB - Morphological traits provide the interface between species and their environment.
For example, body size affects the fitness of individuals in various ways. Yet
especially for ectotherms, the applicability of general rules of interspecific
clines of body size and even more so of other morphological traits is still under
debate. Here we tested relationships between elevation (as a proxy for
temperature) and productivity with four ecologically relevant morphological
traits of orthopteran assemblages that are related to fecundity (body size),
dispersal (wing length), jumping ability (hind femur length), and predator
detection (eye size). We measured traits of 160 orthopteran species that were
sampled along an extensive environmental gradient at Mt. Kilimanjaro (Tanzania),
spanning elevations from 790 to 4,410 m above sea level (a.s.l.) with different
levels of plant productivity. For traits other than body size, we calculated the
residuals from a regression on body length to estimate the variation of traits
irrespective of body size. Bayesian analyses revealed that mean body size of
assemblages, as well as the means of relative wing length, hind femur length, and
eye size, decreased with increasing elevation. Body size and relative eye size
also decreased with increasing productivity. Both phylogenetic relationships, as
well as species-specific adaptations, contributed to these patterns. Our results
suggest that orthopteran assemblages had higher fecundity and better dispersal
and escape abilities, as well as better predator detection at higher temperatures
(low elevations) than at low temperatures (high elevations). Large body sizes
might be advantageous in habitats with low productivity because of a reduced risk
of starvation. Likewise, large eye size might be advantageous because of the
ability to detect predators in habitats with low vegetation cover, where hiding
possibilities are scarce. Our study highlights that changes in temperature and
productivity not only lead to interspecific changes in body size but are also
related to independent changes of other morphological traits that influence the
ecological fit of organisms in their environment.
PMID- 29944732
TI - Pricing Storm Surge Risks in Florida: Implications for Determining Flood
Insurance Premiums and Evaluating Mitigation Measures.
AB - The National Flood Insurance Program (NFIP) has been criticized for inaccurate
flood hazard maps and premiums that are not risk based. We employ granular storm
surge data comprised of five different event probabilities with associated flood
elevations to calculate surge risk-based premiums for homes in Pensacola,
Florida, which we compare with NFIP premiums that are based on flood risk data
with only one event probability (1% annual chance floods). We demonstrate how
more granular flood risk data used for calculating risk-based insurance premiums
should be part of the NFIP mapping and rate-setting processes. We then examine
three different sea-level rise (SLR) scenarios specific to Pensacola from the
National Oceanic and Atmospheric Administration (NOAA), and assess surge risk
based premiums out to 2100. We analyze the cost effectiveness of elevating homes
to mitigate surge risks when costs of elevation are one lump upfront sum, and
when costs are spread over 30 years via low-interest mitigation loans. Benefits
are the avoided future losses from surge risks going out to 2100 with the three
different SLR scenarios. Findings show that it is cost effective to elevate high
value homes with low first-floor elevations in the most risky surge zones.
Spreading costs of elevation with 30-year loans should be directed at low-income
households to address affordability concerns. Alternative flood mitigation
actions, such as wet floodproofing and elevating electrical and plumbing
utilities, should be considered in instances where elevation is not cost
effective.
PMID- 29944731
TI - The challenge of acquiring a satisfactory EBSD result of CWSR Zircaloy-4 cladding
tube.
AB - : This work presents a methodology combining SEM, EDS, conventional EBSD, and
transmission-EBSD to analyse a recrystallised Zircaloy-4 sheet and cold-worked
stress-relieved (CWSR) Zircaloy-4 cladding in unprecedented detail. Second-phase
precipitates (SPPs) in Zircaloy-4 specimens were revealed after chemical
polishing using a solution containing hydrofluoric acid (HF). Pitting corrosion
of Zircaloy-4 specimens was revealed after electropolishing using an electrolyte
containing HClO4 . A zirconium coupon without SPPs was used to confirm the
chemical response of SPPs on surface morphology. Intrinsic features of cold
worked Zircaloy-4 such as relatively small grain sizes, high dislocation density,
and complex microstructure make it significantly more difficult to collect
excellent EBSD results compared to recrystallised Zircaloy-4. The fine hydride
structure of as-hydrided CWSR Zircaloy-4 cladding further increases the level of
challenge on EBSD analysis. LAY DESCRIPTION: We present a methodology combining
multiple microscopic methods to analyse a recrystallised Zircaloy-4 sheet and
cold-worked stress-relieved (CWSR) Zircaloy-4 cladding, important alloys of
structural materials widely used in nuclear application, and emphasis on the
challenge of acquiring a satisfactory electron backscatter diffraction (EBSD)
result of CWSR Zircaloy-4 cladding material in great details. EBSD is a powerful
technique to characterise the crystallographic distribution and lattice type of
conductive crystalline materials, especially for a highly textured material like
CWSR Zircaloy-4 alloy. However, zirconium alloys are known to be one of the most
difficult materials to prepare for EBSD characterisation. We point out that the
configuration of the microstructure of the specimen cause the challenge in the
EBSD sample preparations. Moreover, the occurrence of tiny zirconium hydride
precipitates in Zircaloy-4 increases the difficulty. We believe that the
information of the EBSD sample preparation related results in this paper can
provide researchers and scientists in this community a useful reference to speed
up the EBSD sample preparation of CWSR Zircaloy-4 cladding material and to expect
the corresponding EBSD results.
PMID- 29944733
TI - Dynamics of loops at the substrate entry channel determine the specificity of
iridoid synthases.
AB - Iridoid synthases belong to the family of short-chain dehydrogenase/reductase
involved in the biosynthesis of iridoids. Despite having high sequence and
structural homology with progesterone 5beta-reductase, these enzymes exhibit
differential substrate specificities. Previously, two loops, L1 and L2 at
substrate-binding pocket, were suggested to be involved in generating substrate
specificity. However, the structural basis of specificity determinants was
elusive. Here, combining sequence and structural analysis, site-directed
mutagenesis, and molecular dynamics simulations, we have shown that iridoid
synthase contains two channels for substrate entry whose geometries are altered
by L1-L2 dynamics, primarily orchestrated by interactions of residues Glu161 and
Gly162 of L1 and Asn358 of L2. A complex interplay of these interactions confer
the substrate specificity to the enzyme.
PMID- 29944734
TI - Are fine-needle aspiration biopsy-derived cell blocks a useful surrogate for
tissue samples in breast cancer?
AB - AIMS: The diagnosis of breast cancer (BC) is based on clinical examination in
combination with imaging, and confirmed by pathological assessment of core needle
biopsy or fine-needle aspiration biopsy (FNAB). The biological profile of the
lesion is needed to define the prognosis and establish therapy. Given the
importance of an early and minimally invasive diagnosis, we aimed to verify
whether the biological features detected in FNAB-derived cytological material
reflect the biological characteristics of surgical samples. METHODS AND RESULTS:
We used immunohistochemistry and fluorescence in-situ hybridisation to study a
panel of conventional biomarkers [oestrogen receptor (ER), progesterone receptor
(PgR), Ki67, and human epidermal growth factor receptor 2 (HER2)] in FNAB-derived
cytological samples included in cell blocks of 93 BC patients, and compared the
results with those obtained from histological evaluation of the same parameters
in surgical samples. Median immunopositive values of ER, PgR and Ki67 were
similar in cell blocks and surgical samples. The concordance rates of ER and PgR
between FNAB-derived cell blocks and histological samples were 98% and 84%,
respectively. The concordance rates of Ki67 and HER2 between the two sample types
were 90% and 96%, respectively. Tumour subtype classification for triple-negative
and HER2-positive BCs in FNAB-derived cell blocks was always concordant with the
subtype determined in surgical material. CONCLUSIONS: We demonstrated that
biological marker determination in FNAB-derived cell blocks is feasible, and
provides useful information and comparable results to those obtained with
histological evaluation. Given the low cost of the procedure and its minimal
impact on patients, we believe that cytological samples could be used as an
alternative to tissue samples for early BC biomarker evaluation.
PMID- 29944735
TI - Adherence, knowledge, and perception about oral anticoagulants in patients with
atrial fibrillation at high risk for thromboembolic events after radiofrequency
ablation.
AB - AIMS: This study aimed to: (a) determine adherence rates to oral anticoagulants
in atrial fibrillation patients with a high risk for thromboembolic events
postradiofrequency ablation; (b) evaluate patients' knowledge and perceptions
towards oral anticoagulants; and (c) explore the impact of patients' knowledge
and perceptions on treatment adherence. BACKGROUND: Atrial fibrillation is a
common arrhythmia associated with an increased risk of developing thromboembolic
events such as stroke. Although adherence to oral anticoagulants is crucial to
prevent such complications, the relationship between adherence, knowledge and
patient perceptions is poorly understood in patients with atrial fibrillation at
high risk for thromboembolic events after radiofrequency ablation. DESIGN: A
cross-sectional observational survey study was performed in a single centre.
METHODS: The levels of adherence, knowledge, and perception towards oral
anticoagulants were assessed using the 8-item Morisky Medication Adherence Scale,
Knowledge of Oral Anticoagulation Tool, Perception of Anticoagulant Treatment
Questionnaire and Benefit-Risk Perception Tool, respectively. Results from these
self-reported tools were analysed descriptively. A multivariable binary logistic
regression model was used to identify factors associated with levels of adequate
adherence. RESULTS: Adequate treatment adherence was found in three-quarters of
patients. The total mean knowledge score was low. Participants expressed high
ease of use and low burden of treatment. Higher total knowledge and satisfaction
scores were significant factors associated with higher levels of adherence.
CONCLUSION: There remains a huge unmet need to follow-up and educate patients
with atrial fibrillation, focusing on good knowledge and correct perception of
the advantages and disadvantages of oral anticoagulants. Our results suggest that
increased knowledge and satisfaction rates might have a positive impact on
adherence to oral anticoagulants.
PMID- 29944736
TI - A novel U-shaped relationship between BMI and risk of generalized aggressive
periodontitis in Chinese: A cross-sectional study.
AB - BACKGROUND: Association between BMI and periodontitis were controversial. A study
indicated that not only overweight or obesity but also underweight was correlated
with generalized aggressive periodontitis (GAgP). However, the exact relationship
between BMI and GAgP and the optimal BMI value for the lowest risk of GAgP remain
unknown. OBJECTIVE: To explore the exact relationship between BMI and GAgP risk,
periodontal status and WBC (white blood cell) count and find the optimal BMI
value associated with the lowest risk, periodontal status and lowest WBC of GAgP
in Chinese. MATERIAL AND METHODS: 300 GAgP patients and 133 healthy controls were
recruited. Height and weight of participants were accurately measured to
calculate BMI value. Clinical periodontal parameters, including probing depth
(PD), attachment loss (AL), and bleeding index (BI) were recorded. WBC was
obtained from routine blood examination. Smooth curve fitting and segmented
regression model were used to analyze the threshold effect between BMI and
variables. The shape of the curve was used to describe the relationships between
BMI and GAgP. RESULTS: U-shaped relationships between BMI and risk of GAgP, AL,
and WBC count in GAgP patients were observed. The optimal value of BMI for the
lowest risk of GAgP and lowest WBC count was 22 kg/m2 . The risk of GAgP
increased by 39% in patients per unit increase of BMI when BMI ranged from 22 to
28 kg/m2 (adjusted OR = 1.39, 95% CI: 1.17, 1.67) and increased by 18% per unit
decrease of BMI when BMI ranged from 22 to 18 kg/m2 (adjusted OR = 0.82, 95% CI:
0.69, 0.97). The count of WBC increased by 1.12 * 109 /L in patients per unit
increase of BMI when BMI ranged from 22 to 28 kg/m2 (adjusted beta = 0.12, 95%
CI: 0.01, 0.23) and increased by 0.2 * 109 /L per unit decrease of BMI when BMI
ranged from 22 to18 kg/m2 (adjusted beta = -0.2, 95% CI: -0.35, -0.04).
CONCLUSION: U-shaped relationships exist between BMI and risk of GAgP, AL, and
WBC count in patients with GAgP among Chinese aged below 36 years old with their
BMI range from 18 to 28 kg/m2 ; the optimal BMI value for lowest odds ratio and
lowest WBC count of GAgP was 22 kg/m2 .
PMID- 29944738
TI - Agent-Based Models as an Integrating Boundary Object for Interdisciplinary
Research.
AB - Many of the most complicated and pressing problems in hazards research require
the integration of numerous disciplines. The lack of a common knowledge base,
however, often prohibits clear communication and interaction among
interdisciplinary researchers, sometimes leading to unsuccessful outcomes.
Drawing on experience with several projects and collective expertise that spans
multiple disciplines, the authors argue that a promising way to enhance
participation and enable communication is to have a common model, or boundary
object, that can integrate knowledge from different disciplines. The result is
that researchers from different disciplines who use different research methods
and approaches can work together toward a shared goal. This article offers four
requirements for boundary objects that may enhance hazards research. Based on
these requirements, agent-based models have the necessary characteristics to be a
boundary object. The article concludes by examining both the value of and the
challenges from using agent-based models as the boundary object in
interdisciplinary projects.
PMID- 29944739
TI - Identification of a recurrent mutation in ATP2C1 demonstrates that papular
acantholytic dyskeratosis and Hailey-Hailey disease are allelic disorders.
PMID- 29944737
TI - The prevalence and clinical associations of hypovitaminosis D in pregnant women
from Brazil.
AB - OBJECTIVE: To study the prevalence and the clinical and demographic associations
of hypovitaminosis D in pregnant women from southern Brazil. METHODS: In this
cross-sectional study, pregnant women attending prenatal care at two university
clinics in Curitiba, Brazil, were investigated for clinical and demographic data
and for serum levels of vitamin D, calcium, and parathyroid hormone. Data were
collected during summer (January 26 to March 4, 2016) or winter (July 28 to
August 31, 2016). RESULTS: The study included 520 women, with 264 studied in
winter and 256 in summer. The median vitamin D level was 53.41 nmol/L; 227
(43.7%) women had vitamin D deficiency (<49.92 nmol/L), 193 (37.1%) had vitamin D
insufficiency, and 100 (19.2%) had a normal level (>=74.88 nmol/L). The vitamin D
serum level was linked to the season (P<0.001) and the body mass index (P=0.026).
Women with HIV infections had a lower prevalence and women with pre-eclampsia had
a higher prevalence of hypovitaminosis D (P<0.001 and P=0.025, respectively). The
association between pre-eclampsia and low vitamin D status was independent of
body mass index, tobacco exposure, maternal age, and pregnancy duration (P=0.043;
odds ratio 1.014-2.795). CONCLUSION: The rate of hypovitaminosis D in pregnant
women from southern Brazil was high. Hypovitaminosis D was more common in winter
and was associated with pre-eclampsia.
PMID- 29944740
TI - EQUAL Aspergillosis Score 2018: An ECMM score derived from current guidelines to
measure QUALity of the clinical management of invasive pulmonary aspergillosis.
AB - Invasive pulmonary aspergillosis is a serious threat to immunocompromised and
critical care patients. Recent detailed guidelines and treatment algorithms lead
microbiologists and clinicians in diagnosis and treatment of invasive
aspergillosis. Currently, there is no tool available that allows to measure
guideline adherence. To develop such a tool, we reviewed current guidelines
provided by five scientific societies (European Society for Clinical Microbiology
and Infectious Diseases, European Confederation of Medical Mycology, European
Respiratory Society, Infectious Diseases Society of America (IDSA), and
Infectious Diseases Working Party of the German Society for Hematology and
Medical Oncology) and selected the strongest recommendations for management as
key components for our scoring tool. We integrated diagnostic measures (chest
computed tomography, bronchoalveolar lavage with galactomannan, fungal culture,
fungal polymerase chain reaction analysis, species identification, susceptibility
testing, histology with silver stain, Periodic acid-Schiff staining, and
molecular diagnostics), treatment (antifungal choice and therapeutic drug
monitoring), and follow-up computed tomography. The EQUAL Aspergillosis Score
2018 aggregates and weighs the components and provides a tool to support
antifungal stewardship and to quantify guideline adherence.
PMID- 29944742
TI - The importance of accounting for imperfect detection when estimating functional
and phylogenetic community structure.
AB - Incorporating imperfect detection when estimating species richness has become
commonplace in the past decade. However, the question of how imperfect detection
of species affects estimates of functional and phylogenetic community structure
remains untested. We used long-term counts of breeding bird species that were
detected at least once on islands in a land-bridge island system, and employed
multi-species occupancy models to assess the effects of imperfect detection of
species on estimates of bird diversity and community structure by incorporating
species traits and phylogenies. Our results showed that taxonomic, functional,
and phylogenetic diversity were all underestimated significantly as a result of
species' imperfect detection, with taxonomic diversity showing the greatest bias.
The functional and phylogenetic structure calculated from observed communities
were both more clustered than those from the detection-corrected communities due
to missed distinct species. The discrepancy between observed and estimated
diversity differed according to the measure of biodiversity employed. Our study
demonstrates the importance of accounting for species' imperfect detection in
biodiversity studies, especially for functional and phylogenetic community
ecology, and when attempting to infer community assembly processes. With datasets
that allow for detection-corrected community structure, we can better estimate
diversity and infer the underlying mechanisms that structure community assembly,
and thus make reliable management decisions for the conservation of biodiversity.
PMID- 29944741
TI - Combined neuropathological pathways account for age-related risk of dementia.
AB - OBJECTIVE: Our objectives were to characterize the inter-relation of known
dementia-related neuropathologies in one comprehensive model and quantify the
extent to which accumulation of neuropathologies accounts for the association
between age and dementia. METHODS: We used data from 1,362 autopsied participants
of three community-based clinicopathological cohorts: the Religious Orders Study,
the Rush Memory and Aging Project, and the Minority Aging Research Study. We
estimated a series of structural equation models summarizing a priori
hypothesized neuropathological pathways between age and dementia risk
individually and collectively. RESULTS: At time of death (mean age, 89 years),
44% of our sample had a clinical dementia diagnosis. When considered
individually, our vascular, amyloid/tau, neocortical Lewy body, and TAR DNA
binding protein 43 (TDP-43)/hippocampal sclerosis pathology pathways each
accounted for a substantial proportion of the association between age and
dementia. When considered collectively, the four pathways fully accounted for all
variance in dementia risk previously attributable to age. Pathways involving
amyloid/tau, neocortical Lewy bodies, and TDP-43/hippocampal sclerosis were
interdependent, attributable to the importance of amyloid beta plaques in all
three. The importance of the pathways varied, with the vascular pathway
accounting for 32% of the association between age and dementia, wheraes the
remaining three inter-related degenerative pathways together accounted for 68%
(amyloid/tau, 24%; the Lewy body, 1%; and TDP-43/hippocampal sclerosis, 43%).
INTERPRETATION: Age-related increases in dementia risk can be attributed to
accumulation of multiple pathologies, each of which contributes to dementia risk.
Multipronged approaches may be necessary if we are to develop effective
therapies. Ann Neurol 2018;84:10-22.
PMID- 29944743
TI - Assessment of a pan-dermatophyte nested-PCR compared with conventional methods
for direct detection and identification of dermatophytosis agents in animals.
AB - Conventional direct microscopy with potassium hydroxide (KOH) and culture were
found to lack the ability to establish a fast and specific diagnosis of
dermatophytosis. A pan-dermatophyte nested-PCR assay was developed using a novel
primer pair targeting the translation elongation factor 1-alpha (Tef-1alpha)
sequences for direct detection and identification of most veterinary relevant
dermatophytes in animal samples suspected to dermatophytosis. A total of 140
animal skin and hair samples were subjected to direct microscopy, culture, and
ITS-RFLP/ITS-sequencing of culture isolates for the detection and identification
of dermatophytosis agents. Nested-PCR sequencing was performed on all the
extracted DNAs using a commercial kit after dissolving the specimens by
mechanical beating. Nested-PCR was positive in 90% of samples, followed by direct
microscopy (85.7%) and culture (75%). The degree of agreement between nested-PCR
and direct microscopy (94.4%) was higher than with culture (83.3%). In 105
culture-positive cases, the measures of agreement for the identification of
dermatophytosis agents were as follows: 100% between nested-PCR sequencing and
ITS-RFLP/ITS-sequencing and 63.8% between nested-PCR sequencing and culture. The
developed nested-PCR was faster as well as more sensitive and specific than
conventional methods for detection and identification of dermatophytes in
clinical samples, which was particularly suitable for epidemiological studies.
PMID- 29944745
TI - Comparison of conventional radiography and computed tomography as aids in the
diagnosis of osteomyelitis in 11 foals.
AB - BACKGROUND: Conventional radiography is currently the most common imaging
modality used by veterinarians investigating foals with suspected osteomyelitis.
Emerging evidence in adult horses and humans suggests computed tomography (CT) is
a superior modality for evaluation of osseous changes in general. This study
aimed to evaluate the potential benefits of CT versus conventional radiography in
cases of osteomyelitis in foals. METHODS: Cases of osteomyelitis in foals under 6
months of age admitted over a 6-year period at a single referral hospital that
had both CT and conventional radiography images were retrieved. Case details and
measurements of the largest area of bone lysis identified in two planes
(lateromedial/sagittal and dorsopalmar/dorsal) were evaluated by three
veterinarians with a range of experience. RESULTS: A significant difference
regarding lesion size was seen on the lateromedial (LM) radiographic projections
compared with the equivalent sagittal plane CT image. The LM radiographic
evaluation resulted in a 37% underestimation of the area of the lesion.
Additionally, use of the LM radiographic projections were 2.5-fold more variable
in the measurement area compared with CT. In general, regardless of projection,
CT produced more information regarding lesion area and, in some cases, detected
osseous changes that were not evident on the radiographs. CLINICAL RELEVANCE: LM
radiographic projections are less reliable and commonly result in an under
appreciation of lesion size and extent. CT detected lesions that were difficult
or impossible to identify on radiographs and may allow improved treatment
planning.
PMID- 29944744
TI - Seroprevalence and associated risk factors of mosquito-borne alphaviruses in
horses in northern Queensland.
AB - OBJECTIVE: To investigate the seroprevalence and associated risk factors of
alphaviruses (Ross River virus (RRV), Barmah Forest virus (BFV) and Whataroa
virus (WHAV)) in northern Queensland horses. METHODS: A cross-sectional study of
alphavirus antibodies in horses (n = 287) from 147 properties in northern
Queensland from September 2013 to June 2014 was conducted. Owners of sampled
horses were interviewed on potential risk factors. Data were analysed for
associations using multivariable logistic regression. RESULTS: Antibody titres
for RRV were demonstrated in samples from 134 properties (91%; 95% confidence
interval (CI) 87-96%); 22 properties (15%) had BFV reactors (95% CI 12-18%) and 2
properties (1.4%) had WHAV reactors (95% CI -0.5-3.2%). The highest
seroprevalence of RRV was in the Townsville-Burdekin region (93%; 95% CI 90-96%)
followed by the Mackay-Whitsunday (90%; 95% CI 88-98%) and Far North Coast
Tableland (82%; 95% CI 74-90%) regions. No association (P <= 0.05) could be shown
between any of the viruses and age groups, sexes, annual average temperature,
degree of rainfall or proximity to wet environments. An association with reported
large numbers of mosquitoes was seen for RRV but not BFV. A significant
association between properties in close proximity to poultry and pigs was shown
for BFV. CONCLUSION: RRV is endemic within the horse population of northern
Queensland, but horses exhibit few clinical signs and could play a role as
amplifying hosts in the tropics. Exposure of horses to BFV is significant in
northern Queensland and it should be considered a differential diagnosis for RRV.
WHAV warrants further study.
PMID- 29944746
TI - BVDV in Australian alpacas: natural infection and clinical profiles following co
mingling with a persistently infected heifer.
AB - BACKGROUND: Although predominantly a disease of cattle, bovine viral diarrhoea
virus (BVDV) is known to infect other ruminant and camelid species such as sheep
and alpacas. The aims of this study were to determine if BVDV-naive alpacas would
become acutely infected and seroconvert to the predominant Australian strain of
BVDV following co-mingling with a BVDV-1c persistently infected (PI) heifer and
to determine what, if any, clinical signs, haematological responses and selected
biochemical changes occur with acute BVDV-1c infections in alpacas. METHODS: A PI
heifer and four alpacas co-mingled for 2 weeks. Weekly blood samples were
collected and twice weekly clinical examinations were performed on the alpacas.
RESULTS: Serum analysis by antibody ELISA indicated that all four alpacas were
positive for BVDV-specific antibodies between 35 and 54 days after mixing with
the BVDV-1c PI heifer. Viral antigen was detected by antigen ELISA in two alpacas
on days 21 and 35 after initial mixing. In general, all the physical clinical
parameters measured were normal. Serum biochemical and haematological analyses in
two of the alpacas revealed marginally low sodium, chloride and elevated
potassium concentrations, a lymphocytosis, monocytosis and a neutrophilia at some
point during the study period in either one or both of the alpacas. CONCLUSION:
This study showed that infection in Australian alpacas readily occurs when a BVDV
1c PI bovine co-mingles with naive alpacas and that acute infections are
clinically mild and undetectable without serological testing.
PMID- 29944747
TI - Laparoscopic transection of restrictive bands of the mesosalpinx as adjunct to
the use of prostaglandin E2 for mares with suspected uterine tubal blockage.
AB - OBJECTIVE: To describe the laparoscopic transection of restrictive bands of the
mesosalpinx as a useful adjunct to the topical application of prostaglandin E2 to
treat mares with suspected uterine tubal blockage. METHODS: A standard left flank
laparoscopic approach was made to the abdomen using three laparoscopic portals.
If restrictive bands of the mesosalpinx were observed traversing the uterine tube
perpendicularly, they were carefully transected and 1 mg of prostaglandin E2 was
then applied to the external surface of the uterine tube. Skin incisions were
closed with surgical staples and the procedure was repeated on the right uterine
tube. RESULTS: Nine Thoroughbred mares suspected of uterine tubal blockage were
treated. The treated mares had been barren for 1.8 years on average (range: 1-5
years). The overall postoperative conception rate in treated mares was 89% (8/9
mares). The mean number of mated oestrus cycles before pregnancy in the eight
mares that conceived was 1.9 +/- 1.6. These mares had been bred on average 6.2 +/
1.9 cycles without becoming pregnant prior to surgery. CONCLUSION: Transection
of restrictive bands of the mesosalpinx is easily performed as an adjunctive
procedure to laparoscopic-guided application of prostaglandin E2 to the uterine
tube. The procedure does not appear to have any detrimental effects on fertility
and may improve fertility in a particular subset of mares with complicated
uterine tubal disease.
PMID- 29944751
TI - A vision splendid; visioning for the future of occupational therapy.
PMID- 29944750
TI - Can neutral dietary cation-anion difference (DCAD) decrease occurrence of
clinical periparturient hypocalcaemia in dairy cattle?
AB - BACKGROUND: Adjusting the dietary cation-anion difference (DCAD) is one of the
most efficient ways to stimulate calcium homeostasis in periparturient dairy
cattle. However, adjusting DCAD to the recommended negative values (-100 to -150
mEq/kg) is associated with decreased food intake and metabolic acidosis. The
critical conditions of the animals at peripartum (i.e. drastic hormonal changes,
decreased appetite and negative energy balance) can be detrimental to the health,
productivity and welfare of the animals if combined with decreased feed intake
caused by unpalatable acidogenic salts. METHODS: In a cross-sectional study, we
analysed the ration of eight small to large dairy herds with intensive husbandry
systems, including 6949 dry cows. Sodium, potassium, chlorine and sulfur
concentrations in the feed were determined and DCAD was calculated. The DCAD of
the ration of the farms ranged from -33.5 to +24.7 mEq/kg. Parturient paresis
(PP, or milk fever) prevalence was investigated and correlated to DCAD values.
RESULTS: Clinical PP occurrence in the dairies of this investigation on average
declined by 87% (ranging from a 97% decline to 5% increase). This indicates that
adjusting DCAD at neutral values (0 +/- 30 mEq/kg range) may both lower the PP
prevalence and increase ration palatability by lowering acidogenic salts in the
ration. CONCLUSIONS: Further research is recommended to investigate the effects
of neutral DCAD on subclinical hypocalcaemia and food intake of the cattle.
PMID- 29944752
TI - Knowledge translation in the context of the Asia Pacific region.
PMID- 29944754
TI - iReceptor: A platform for querying and analyzing antibody/B-cell and T-cell
receptor repertoire data across federated repositories.
AB - Next-generation sequencing allows the characterization of the adaptive immune
receptor repertoire (AIRR) in exquisite detail. These large-scale AIRR-seq data
sets have rapidly become critical to vaccine development, understanding the
immune response in autoimmune and infectious disease, and monitoring novel
therapeutics against cancer. However, at present there is no easy way to compare
these AIRR-seq data sets across studies and institutions. The ability to combine
and compare information for different disease conditions will greatly enhance the
value of AIRR-seq data for improving biomedical research and patient care. The
iReceptor Data Integration Platform (gateway.ireceptor.org) provides one
implementation of the AIRR Data Commons envisioned by the AIRR Community (airr
community.org), an initiative that is developing protocols to facilitate sharing
and comparing AIRR-seq data. The iReceptor Scientific Gateway links distributed
(federated) AIRR-seq repositories, allowing sequence searches or metadata queries
across multiple studies at multiple institutions, returning sets of sequences
fulfilling specific criteria. We present a review of the development of
iReceptor, and how it fits in with the general trend toward sharing genomic and
health data, and the development of standards for describing and reporting AIRR
seq data. Researchers interested in integrating their repositories of AIRR-seq
data into the iReceptor Platform are invited to contact support@ireceptor.org.
PMID- 29944756
TI - Germinal center responses to complex antigens.
AB - Germinal centers (GCs) are the primary sites of antibody affinity maturation,
sites where B-cell antigen-receptor (BCR) genes rapidly acquire mutations and are
selected for increasing affinity for antigen. This process of hypermutation and
affinity-driven selection results in the clonal expansion of B cells expressing
mutated BCRs and acts to hone the antibody repertoire for greater avidity and
specificity. Remarkably, whereas the process of affinity maturation has been
confirmed in a number of laboratories, models for how affinity maturation in GCs
operates are largely from studies of genetically restricted B-cell populations
competing for a single hapten epitope. Much less is known about GC responses to
complex antigens, which involve both inter- and intraclonal competition for many
epitopes. In this review, we (i) compare current methods for analysis of the GC B
cell repertoire, (ii) describe recent studies of GC population dynamics in
response to complex antigens, discussing how the observed repertoire changes
support or depart from the standard model of clonal selection, and (iii)
speculate on the nature and potential importance of the large fraction of GC B
cells that do not appear to interact with native antigen.
PMID- 29944757
TI - Predicting the spectrum of TCR repertoire sharing with a data-driven model of
recombination.
AB - Despite the extreme diversity of T-cell repertoires, many identical T-cell
receptor (TCR) sequences are found in a large number of individual mice and
humans. These widely shared sequences, often referred to as "public," have been
suggested to be over-represented due to their potential immune functionality or
their ease of generation by V(D)J recombination. Here, we show that even for
large cohorts, the observed degree of sharing of TCR sequences between
individuals is well predicted by a model accounting for the known quantitative
statistical biases in the generation process, together with a simple model of
thymic selection. Whether a sequence is shared by many individuals is predicted
to depend on the number of queried individuals and the sampling depth, as well as
on the sequence itself, in agreement with the data. We introduce the degree of
publicness conditional on the queried cohort size and the size of the sampled
repertoires. Based on these observations, we propose a public/private sequence
classifier, "PUBLIC" (Public Universal Binary Likelihood Inference Classifier),
based on the generation probability, which performs very well even for small
cohort sizes.
PMID- 29944758
TI - The sequences encoded by immunoglobulin diversity (DH ) gene segments play key
roles in controlling B-cell development, antigen-binding site diversity, and
antibody production.
AB - Although at first glance the diversity of the immunoglobulin repertoire appears
random, there are a number of mechanisms that act to constrain diversity. For
example, key mechanisms controlling the diversity of the third complementarity
determining region of the immunoglobulin heavy chain (CDR-H3) include natural
selection of germline diversity (DH ) gene segment sequence and somatic selection
upon passage through successive B-cell developmental checkpoints. To test the
role of DH gene segment sequence, we generated a panel of mice limited to the use
of a single germline or frameshifted DH gene segment. Specific individual amino
acids within core DH gene segment sequence heavily influenced the absolute
numbers of developing and mature B-cell subsets, antibody production, epitope
recognition, protection against pathogen challenge, and susceptibility to the
production of autoreactive antibodies. At the tip of the antigen-binding loop
(PDB position 101) in CDR-H3, both natural (germline) and somatic selection
favored tyrosine while disfavoring the presence of hydrophobic amino acids.
Enrichment for arginine in CDR-H3 appeared to broaden recognition of epitopes of
varying hydrophobicity, but led to diminished binding intensity and an increased
likelihood of generating potentially pathogenic dsDNA-binding autoreactive
antibodies. The phenotype of altering the sequence of the DH was recessive for T
independent antibody production, but dominant for T-cell-dependent responses. Our
work suggests that the antibody repertoire is structured, with the sequence of
individual DH selected by evolution to preferentially generate an apparently
preferred category of antigen-binding sites. The result of this structured
approach appears to be a repertoire that has been adapted, or optimized, to
produce protective antibodies for a wide range of pathogen epitopes while
reducing the likelihood of generating autoreactive specificities.
PMID- 29944755
TI - Immunoglobulin gene analysis as a tool for investigating human immune responses.
AB - The human immunoglobulin repertoire is a hugely diverse set of sequences that are
formed by processes of gene rearrangement, heavy and light chain gene assortment,
class switching and somatic hypermutation. Early B cell development produces
diverse IgM and IgD B cell receptors on the B cell surface, resulting in a
repertoire that can bind many foreign antigens but which has had self-reactive B
cells removed. Later antigen-dependent development processes adjust the antigen
affinity of the receptor by somatic hypermutation. The effector mechanism of the
antibody is also adjusted, by switching the class of the antibody from IgM to one
of seven other classes depending on the required function. There are many
instances in human biology where positive and negative selection forces can act
to shape the immunoglobulin repertoire and therefore repertoire analysis can
provide useful information on infection control, vaccination efficacy, autoimmune
diseases, and cancer. It can also be used to identify antigen-specific sequences
that may be of use in therapeutics. The juxtaposition of lymphocyte development
and numerical evaluation of immune repertoires has resulted in the growth of a
new sub-speciality in immunology where immunologists and computer
scientists/physicists collaborate to assess immune repertoires and develop models
of immune action.
PMID- 29944760
TI - The Bayesian optimist's guide to adaptive immune receptor repertoire analysis.
AB - Probabilistic modeling is fundamental to the statistical analysis of complex
data. In addition to forming a coherent description of the data-generating
process, probabilistic models enable parameter inference about given datasets.
This procedure is well developed in the Bayesian perspective, in which one infers
probability distributions describing to what extent various possible parameters
agree with the data. In this paper, we motivate and review probabilistic modeling
for adaptive immune receptor repertoire data then describe progress and prospects
for future work, from germline haplotyping to adaptive immune system deployment
across tissues. The relevant quantities in immune sequence analysis include not
only continuous parameters such as gene use frequency but also discrete objects
such as B-cell clusters and lineages. Throughout this review, we unravel the many
opportunities for probabilistic modeling in adaptive immune receptor analysis,
including settings for which the Bayesian approach holds substantial promise
(especially if one is optimistic about new computational methods). From our
perspective, the greatest prospects for progress in probabilistic modeling for
repertoires concern ancestral sequence estimation for B-cell receptor lineages,
including uncertainty from germline genotype, rearrangement, and lineage
development.
PMID- 29944759
TI - Understanding B-cell activation and autoantibody repertoire selection in systemic
lupus erythematosus: A B-cell immunomics approach.
AB - Understanding antibody repertoires and in particular, the properties and fates of
B cells expressing potentially pathogenic antibodies is critical to define the
mechanisms underlying multiple immunological diseases including autoimmune and
allergic conditions as well as transplant rejection. Moreover, an integrated
knowledge of the antibody repertoires expressed by B cells and plasma cells (PC)
of different functional properties and longevity is essential to develop new
therapeutic strategies, better biomarkers for disease segmentation, and new
assays to measure restoration of B-cell tolerance or, at least, of normal B-cell
homeostasis. Reaching these goals, however, will require a more precise
phenotypic, functional and molecular definition of B-cell and PC populations, and
a comprehensive analysis of the antigenic reactivity of the antibodies they
express. While traditionally hampered by technical and ethical limitations in
human experimentation, new technological advances currently enable investigators
to address these questions in a comprehensive fashion. In this review, we shall
discuss these concepts as they apply to the study of Systemic Lupus
Erythematosus.
PMID- 29944762
TI - Assessing human B cell repertoire diversity and convergence.
AB - A hallmark of the adaptive immune system is the specificity of B cell and T cell
responses. Mechanistically, this feature relies on the fact that the two genes
that encode B cell and T cell antigen receptors are not germline encoded and
instead are assembled from a large number of small gene segments during
lymphocyte development. The underlying somatic gene recombination process can
generate a quasi-unlimited repertoire of antigen receptors. The high degree of
diversity is essential to guarantee recognition of nearly any antigenic structure
to protect from the large variety of potential invading pathogens and to keep the
balance with commensals. Due to the enormous complexity of the antigen receptor
repertoire, our understanding of its actual size and functional convergence at
the level of the individual and the population is still limited. A better
understanding of the actual degree of diversity could help to predict adaptive
immune responses and would have wide implications for the development of
preventive and therapeutic measures against infectious and autoimmune diseases as
well as cancer. Here, we discuss the recent advances in the field with a specific
focus on B cells and the function of antibodies.
PMID- 29944763
TI - Strength in diversity: Phenotypic, functional, and molecular heterogeneity within
the memory B cell repertoire.
AB - The vast majority of vaccines exploit antibody memory to induce lasting immunity.
Memory B cells are generated during the initial response to infection, but
persist long after the infection has cleared. Immune memory success relies on its
adaptability: in response to different pathogens, variants of a single pathogen,
and in balancing persistence with reactivation and plasma cell differentiation.
This is likely achieved by producing a B cell memory population that is highly
diverse, and recent work has highlighted the importance of memory B cell subsets
in mediating the dichotomous roles of the population. This review will detail the
characterization, function and both intrinsic and extrinsic regulation of
different memory B cell subsets: memory B cell precursors within the germinal
center, phenotypic, and functional heterogeneity of the memory B cell population,
and memory B cell subsets that reside in tissues. In particular, understanding
the genetic and epigenetic regulation of memory B diversity may be critical for
gaining insight into B cell memory responses to pathogens that have evaded
effective vaccine design. Therefore, there is a vital need to understand the
mechanisms underlying the origin, function and translational potential of the
heterogeneity within the memory B cell population.
PMID- 29944764
TI - Characterization of the immunologic repertoire: A quick start guide.
PMID- 29944761
TI - Bohemian T cell receptors: sketching the repertoires of unconventional
lymphocytes.
AB - Over the last several decades, novel populations of unconventional T cells have
been identified; defined by an invariant (or nearly invariant) T cell receptor
(TCR) with a fixed specificity to non-canonical antigens and major
histocompatibility (MHC) molecules, they form large, functionally monoclonal
populations tasked with surveying for their specific antigens. With residence in
both lymphoid and non-lymphoid tissues coupled with their ability to rapidly
produce a spectrum of cytokines and effector molecules, the unconventional T
cells are poised as some of the first responders to infection/damage and are
thought to provide critical coverage before more focused, conventional T cell
responses are mobilized. However, new technologies for the measurement and
characterization of TCR repertoires have identified an underappreciated amount of
TCR diversity in the unconventional T cells. In many cases, the specificities of
these diverse TCRs converge on the same or similar antigens as their invariant
counterparts, while others have yet to be defined. Here, we will review the
current knowledge of the TCR repertoires of unconventional T cells and discuss
how repertoires might be used as a framework for their organization, and further
our understanding of their role not only during an immune response, but also
their contribution in maintaining homeostasis.
PMID- 29944765
TI - Human adaptive immune receptor repertoire analysis-Past, present, and future.
AB - The genes encoding adaptive immune antigen receptors, namely the immunoglobulins
expressed in membrane-bound or secreted forms by B cells, and the cell surface T
cell receptors, are unique in human biology because they are generated by
combinatorial rearrangement of the genomic DNA. The diversity of receptors so
generated in populations of lymphocytes enables the human immune system to
recognize antigens expressed by pathogens, but also underlies the pathological
specificity of autoimmune diseases and the mistargeted immunity in allergies.
Several recent technological developments, foremost among them the invention of
high-throughput DNA sequencing instruments, have enabled much deeper and thorough
evaluation of clones of human B cells and T cells and the antigen receptors they
express during physiological and pathogenic immune responses. The evolutionary
struggles between host adaptive immune responses and populations of pathogens are
now open to greater scrutiny, elucidation of the underlying reasons for
successful or failed immunity, and potential predictive modeling, than ever
before. Here we give an overview of the foundations, recent progress, and future
prospects in this dynamic area of research.
PMID- 29944768
TI - The history of dermatology helps to understand debates of today.
PMID- 29944767
TI - Pioneers in dermatology and venereology: an interview with Prof. Otto Braun
Falco.
PMID- 29944769
TI - Asymmetric Synthesis of Axially Chiral 2-Aminobiaryls by Rhodium-Catalyzed
Benzannulation of 1-Arylalkynes with 2-(Cyanomethyl)phenylboronates.
AB - Asymmetric benzannulation of 1-arylalkynes, where the aryl group is an ortho
substituted aromatic group, with 2-(cyanomethyl)phenylboronate was catalyzed by a
rhodium complex coordinated with a chiral diene ligand to give high yields of
axially chiral 2-aminobiaryls with greater than 90 % ee.
PMID- 29944770
TI - Divergent parasite infections in sympatric cichlid species in Lake Victoria.
AB - Parasitism has been proposed as a factor in host speciation, as an agent
affecting coexistence of host species in species-rich communities and as a driver
of post-speciation diversification. Young adaptive radiations of closely related
host species of varying ecological and genomic differentiation provide
interesting opportunities to explore interactions between patterns of parasitism,
divergence and coexistence of sympatric host species. Here, we explored patterns
in ectoparasitism in a community of 16 fully sympatric cichlid species at Makobe
Island in Lake Victoria, a model system of vertebrate adaptive radiation. We
asked whether host niche, host abundance or host genetic differentiation explains
variation in infection patterns. We found significant differences in infections,
the magnitude of which was weakly correlated with the extent of genomic
divergence between the host species, but more strongly with the main ecological
gradient, water depth. These effects were most evident with infections of
Cichlidogyrus monogeneans, whereas the only host species with a strictly crevice
dwelling niche, Pundamilia pundamilia, deviated from the general negative
relationship between depth and parasitism. In accordance with the Janzen-Connell
hypothesis, we also found that host abundance tended to be positively associated
with infections in some parasite taxa. Data on the Pundamilia sister species
pairs from three other islands with variable degrees of habitat (crevice)
specialization suggested that the lower parasite abundance of P. pundamilia at
Makobe could result from both habitat specialization and the evolution of
specific resistance. Our results support influences of host genetic
differentiation and host ecology in determining infections in this diverse
community of sympatric cichlid species.
PMID- 29944771
TI - Ring-Opening Metathesis Polymerization in Aqueous Media Using a Macroinitiator
Approach.
AB - Water-soluble and amphiphilic polymers are of great interest to industry and
academia, as they can be used in applications such as biomaterials and drug
delivery. Whilst ring-opening metathesis polymerization (ROMP) is a fast and
functional group tolerant methodology for the synthesis of a wide range of
polymers, its full potential for the synthesis of water-soluble polymers has yet
to be realized. To address this, we report a general strategy for the synthesis
of block copolymers in aqueous milieu using a commercially available ROMP
catalyst and a macroinitiator approach. This allows for excellent control in the
preparation of block copolymers in water. If the second monomer is chosen such
that it forms a water-insoluble polymer, polymerization-induced self-assembly
(PISA) occurs and a variety of self-assembled nano-object morphologies can be
accessed.
PMID- 29944772
TI - Multistage Microfluidic Platform for the Continuous Synthesis of III-V Core/Shell
Quantum Dots.
AB - We present a fully continuous chip microreactor-based multistage platform for the
synthesis of quantum dots with heterostructures. The use of custom-designed chip
reactors enables precise control of heating profiles and flow distribution across
the microfluidic channels while conducting multistep reactions. The platform can
be easily reconfigured by reconnecting the differently designed chip reactors
allowing for screening of various reaction parameters during the synthesis of
nanocrystals. III-V core/shell quantum dots are chosen as model reaction systems,
including InP/ZnS, InP/ZnSe, InP/CdS and InAs/InP, which are prepared in flow
using a maximum of six chip reactors in series.
PMID- 29944766
TI - CD4 T cells in protection from influenza virus: Viral antigen specificity and
functional potential.
AB - CD4 T cells convey a number of discrete functions to protective immunity to
influenza, a complexity that distinguishes this arm of adaptive immunity from B
cells and CD8 T cells. Although the most well recognized function of CD4 T cells
is provision of help for antibody production, CD4 T cells are important in many
aspects of protective immunity. Our studies have revealed that viral antigen
specificity is a key determinant of CD4 T cell function, as illustrated both by
mouse models of infection and human vaccine responses, a factor whose importance
is due at least in part to events in viral antigen handling. We discuss research
that has provided insight into the diverse viral epitope specificity of CD4 T
cells elicited after infection, how this primary response is modified as CD4 T
cells home to the lung, establish memory, and after challenge with a secondary
and distinct influenza virus strain. Our studies in human subjects point out the
challenges facing vaccine efforts to facilitate responses to novel and avian
strains of influenza, as well as strategies that enhance the ability of CD4 T
cells to promote protective antibody responses to both seasonal and potentially
pandemic strains of influenza.
PMID- 29944773
TI - A One-Pot "Triple-C" Multicyclization Methodology for the Synthesis of Highly
Constrained Isomerically Pure Tetracyclic Peptides.
AB - A broadly applicable one-pot methodology for the facile transformation of linear
peptides into tetracyclic peptides through a chemoenzymatic peptide
synthesis/chemical ligation of peptides onto scaffolds/copper(I)-catalyzed
reaction (CEPS/CLIPS/CuAAC; "triple-C") locking methodology is reported. Linear
peptides with varying lengths (>=14 amino acids), comprising two cysteines and
two azidohomoalanines (Aha), were efficiently cyclized head-to-tail by using the
peptiligase variant omniligase-1 (CEPS). Subsequent ligation-cyclization with
tetravalent (T41/2 ) scaffolds containing two bromomethyl groups (CLIPS) and two
alkyne functionalities (CuAAC) yielded isomerically pure tetracyclic peptides.
Sixteen different functional tetracycles, derived from bicyclic inhibitors
against urokinase plasminogen activator (uPA) and coagulation factor XIIa
(FXIIa), were successfully synthesized and their bioactivities evaluated. Two of
these (FF-T41/2 ) exhibited increased inhibitory activity against FXIIa, compared
with a bicyclic control peptide. The corresponding hetero-bifunctional variants
(UF/FU-T41/2 ), with a single copy of each inhibitory sequence, exhibited
micromolar activities against both uPA and FXIIa; thus illustrating the potential
of the "bifunctional tetracyclic peptide" inhibitor concept.
PMID- 29944774
TI - Intrinsically Photoswitchable alpha/beta Peptides toward Two-State Foldamers.
AB - A simple, unsaturated, E-Z photoisomerizable beta-amino acid, (Z)-3-aminoprop-2
enoic acid, has been introduced into peptide foldamers through a one-pot chemical
coupling, based on Pd/Cu-catalyzed olefin oxidative amidation, between two
peptide segments carrying, respectively, a -Gly-NH2 residue at the C-terminus and
an acryloyl group at the N-terminus. Reversible conversion between the Z and E
configurations of the 3-aminoprop-2-enoic linkage was achieved photochemically. A
crystallographic analysis on two model compounds shed light on the consequences,
in terms of 3D structure and self-association properties, brought about by the
different configuration of the unsaturated linkage. As a proof of concept, E-Z
photoisomerization of a 3-aminoprop-2-enoic acid residue, inserted as the
junction between two conformationally distinct peptide domains (one helical while
the other beta-sheet promoter), allowed supramolecular self-association to be
reversibly turned on/off.
PMID- 29944775
TI - Modular Preparation of Graphene-Based Functional Architectures through Two-Step
Organic Reactions: Towards High-Performance Energy Storage.
AB - Graphene-based materials have recently attracted much attention due to their
extraordinary physical and chemical properties, which make them attractive
candidates for many technological applications in sensing, optoelectronics,
catalysis, and energy storage. Their chemical functionalization is key to tuning
their properties. Herein, a novel two-step synthetic approach, which enables a
high degree of covalent functionalization of graphene oxide (GO) is devised,
thereby making the facile attachment of various robust functional molecules
possible. Such a process relies initially on the grafting of an ethylenediamine
linker followed by a second step consisting of the condensation reaction between
aldehyde and amine groups to form imine bonds. As test beds, two kinds of
graphene-based functional systems, namely, porphyrin-modified GO and ferrocene
modified GO, are prepared. Such hybrid systems are characterized by various
spectroscopic and microscopic techniques. The degree of functionalization is
quantified as the attachment of one porphyrin or ferrocene unit to every 34 or 77
carbon atoms of the GO scaffold, respectively, which is much higher than that of
values obtained upon using various established chemical approaches to
functionalize GO, such as condensation, cycloaddition, or coupling reactions. For
the first time, the reduced form of ferrocene-modified GO was employed as an
electrode material in supercapacitors, showing a specific capacitance of 127 F g
1 at a current density of 1 A g-1 , with capacitance retention of about 93 %
after 5000 cycles at the same current density; this demonstrates great potential
for application in high-performance energy-storage devices.
PMID- 29944776
TI - Neurally adjusted ventilatory assist in extremely low-birthweight infants.
AB - BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is expected to improve
respiratory outcomes in preterm infants, but it has not yet been evaluated. We
investigated whether NAVA could improve respiratory outcomes and reduce sedation
use in extremely low-birthweight infants (ELBWI). METHODS: A retrospective cohort
study was conducted based on patient charts at the Nagano Children's Hospital
neonatal intensive care unit, Japan. Infants who were born at <27 weeks'
gestation were included. We assessed the prevalence of bronchopulmonary dysplasia
(BPD), home oxygen therapy (HOT), duration of intubation, and sedation use.
RESULTS: The NAVA group consisted of 14 ELBWI who were born at <27 weeks'
gestation between September 2013 and September 2015. A total of 21 ELBWI born
between September 2011 and September 2013, before NAVA implementation, served as
the control group. There were no significant differences in the perinatal
background characteristics between the two groups. For respiratory outcomes, no
significant between-group differences were found in the prevalence of BPD and HOT
or the duration of intubation. The total duration of sedation use was not
significantly different between the two groups, but in the NAVA group, midazolam
was discontinued in all cases after the infants were switched to NAVA.
CONCLUSIONS: NAVA was safe in preterm infants and had a similar effect to
conventional mechanical ventilation with regard to respiratory outcomes and
sedation use in the chronic phase; thus, NAVA could be used in the early phase,
at least before BPD worsens to improve respiratory outcomes in ELBWI.
PMID- 29944777
TI - Birth Outcomes of Women Using a Midwife versus Women Using a Physician for
Prenatal Care.
AB - INTRODUCTION: Few studies have compared midwife-led and physician-led care in the
United States. Our objective was to compare the frequency of birth interventions
and maternal and neonatal outcomes between women who received prenatal care from
a midwife and those who received care from a physician, among women who were low
risk when they initiated prenatal care. METHODS: We performed a retrospective
cohort study of women giving birth at a large public hospital who had at least
one prenatal visit before 20 weeks' gestation in the years 2012 through 2015. We
classified women according to prenatal care provider type (midwife vs physician)
at first prenatal visit and compared birth outcomes between the groups, using
intent-to-treat analyses. We used modified Poisson regression to calculate
adjusted risk ratios (aRRs) for common outcomes and logistic regression with
Firth's bias correction to produce adjusted odds ratios (aORs) for rare outcomes.
As a sensitivity analysis, we performed a matched propensity score analysis to
account for potential confounding by indication. RESULTS: Midwives provided care
to 8.2% of the women; physicians provided care to 91.8% of the women. Women in
midwifery care were less likely to be black, have Medicaid insurance, or have a
history of pregnancy complications or previous cesarean births compared with
women who received care from physicians. Women in midwifery care had lower risks
of cesarean (aRR, 0.66; 95% CI, 0.57-0.78) and preterm birth (aRR, 0.58; 95% CI,
0.42-0.79), with no increased odds of neonatal intensive care unit admissions,
neonatal deaths, or severe maternal morbidity. Women in midwifery care had
increased odds of postpartum hemorrhage and shoulder dystocia (aOR, 3.26; 95% CI,
1.40-7.58, and aOR, 1.80; 95% CI, 1.01-3.22, respectively); however, these did
not remain significant in the propensity score analysis. DISCUSSION: Among women
with low-risk pregnancies, midwifery care was associated with substantially fewer
preterm births and labor interventions.
PMID- 29944778
TI - Modulation of synaptic inputs in magnocellular neurones in a rat model of cancer
cachexia.
AB - In cancer cachexia, abnormal metabolism and neuroendocrine dysfunction cause
anorexia, tissue damage and atrophy, which can in turn alter body fluid balance.
Arginine vasopressin, which regulates fluid homeostasis, is secreted by
magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus.
Arginine vasopressin secretion by MNCs is regulated by both excitatory and
inhibitory synaptic activity, alterations in plasma osmolarity and various
peptides, including angiotensin II. In the present study, we used whole-cell
patch-clamp recordings of brain slices to determine whether hyperosmotic
stimulation and/or angiotensin II potentiate excitatory synaptic input in a rat
model of cancer cachexia, similar to their effects in normal (control) rats.
Hyperosmotic (15 and 60 mmol L-1 mannitol) stimulation and angiotensin II (0.1
MUmol L-1 ) increased the frequency, but not the amplitude, of miniature
excitatory postsynaptic currents in normal rats; in model rats, both effects were
significantly attenuated. These results suggest that cancer cachexia alters
supraoptic MNC sensitivity to osmotic and angiotensin II stimulation.
PMID- 29944779
TI - Towards High Performance Metal-Organic Framework-Microporous Polymer Mixed Matrix
Membranes: Addressing Compatibility and Limiting Aging by Polymer Doping.
AB - Membrane separation for gas purification is an energy-efficient and environment
friendly technology. However, the development of high performance membranes is
still a great challenge. In principle, mixed matrix membranes (MMMs) have the
potential to overcome current materials limitations, but in practice there is no
straightforward method to match the properties of fillers and polymers (the main
components of MMMs) in such a way that the final membrane performance reflects
the high performance of the microporous filler and the processability of the
continuous polymer phase. This issue is especially important when high flux
polymers are utilized. In this work, we demonstrate that the use of small amounts
of a glassy polymer in combination with high performance PIM-1 allow for the
preparation of metal-organic framework (MOF)-based MMMs with superior separation
properties and low aging rates under humid conditions, meeting the commercial
target for post-combustion CO2 capture.
PMID- 29944780
TI - High-Quality Yeast-2-Hybrid Interaction Network Mapping.
AB - In this article, we describe a Y2H interaction mapping protocol for
systematically screening medium-to-large collections of open reading frames
(ORFs) against each other. The protocol is well suited for analysis of focused
networks, for modules of interest, assembling genome-scale interactome maps, and
investigating host-microbe interactions. The four-step high-throughput protocol
has a demonstrated low false-discovery rate that is essential for producing
meaningful network maps. Following the assembly of yeast expression clones from
an existing ORFeome collection, we describe in detail the four-step procedure
that begins with the primary screen using minipools, followed by secondary
verification of primary positives, identification of candidate interaction pairs
by sequencing, and a final verification step using fresh inoculants. In addition
to this core protocol, aspects of network mapping and quality control will be
discussed briefly. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29944781
TI - Risk factors for bronchiolitis severity: A retrospective review of patients
admitted to the university hospital from central region of Slovenia.
AB - AIM: Study's objective was to identify risk factors associated with bronchiolitis
severity. METHODS: A retrospective chart review of all children <2 years old
diagnosed with bronchiolitis at the University Medical Centre Ljubljana between
May 2014 and April 2015, who were treated as outpatients (paediatric emergency
department, PED group) or as inpatients in the standard hospital setting (WARD
group) or in the paediatric intensive care unit (PICU group). Detection of
respiratory viruses in nasopharyngeal swab was accomplished by RT-PCR. Severity
was assessed by Wang Respiratory Score and hospitalization longer than 24 hours.
RESULTS: The study included 761 children. The three most frequently detected
viruses were respiratory syncytial virus (RSV), human rhinovirus (hRV) and human
bocavirus (hBoV) (57.5%, 272/473; 25.6%, 121/473; 18.4%, 87/473). Patient groups
differed in Wang Respiratory Score for the severity of bronchiolitis (P < 0.001).
No differences regarding the causative viruses were found. There was a lower
proportion of children with the presence of more than one virus in PICU group
compared to other two groups (P = 0.017). The three groups significantly differed
in age, birthweight, comorbidities, bronchodilator treatment and antibiotic
usage. However, multiple regression analysis revealed that younger age and the
use of antibiotics were associated with bronchiolitis severity defined as
hospitalization for >24 hours. CONCLUSIONS: Respiratory syncytial virus, hRV and
hBoV were the most frequently detected viruses. The majority of patients admitted
to the PICU had only one virus detected. Younger age and the use of antibiotics
were associated with bronchiolitis severity.
PMID- 29944782
TI - When money meets morality: Human universals and cultural differences.
PMID- 29944784
TI - Spotlights on our sister journals: Angew. Chem. Int. Ed. 27/2018.
PMID- 29944785
TI - Corrigendum: Far-UV-Excited Luminescence of Nitrogen-Vacancy Centers: Evidence
for Diamonds in Space.
PMID- 29944786
TI - Tackling the childhood obesity crisis.
PMID- 29944787
TI - RUNNING ON EMPTY.
PMID- 29944788
TI - We haven't given up the FIGHT.
PMID- 29944789
TI - Sweet DREAMS.
PMID- 29944790
TI - Attacking the itch.
PMID- 29944783
TI - Talking back: Development of the olivocochlear efferent system.
AB - Developing sensory systems must coordinate the growth of neural circuitry
spanning from receptors in the peripheral nervous system (PNS) to multilayered
networks within the central nervous system (CNS). This breadth presents
particular challenges, as nascent processes must navigate across the CNS-PNS
boundary and coalesce into a tightly intermingled wiring pattern, thereby
enabling reliable integration from the PNS to the CNS and back. In the auditory
system, feedforward spiral ganglion neurons (SGNs) from the periphery collect
sound information via tonotopically organized connections in the cochlea and
transmit this information to the brainstem for processing via the VIII cranial
nerve. In turn, feedback olivocochlear neurons (OCNs) housed in the auditory
brainstem send projections into the periphery, also through the VIII nerve. OCNs
are motor neuron-like efferent cells that influence auditory processing within
the cochlea and protect against noise damage in adult animals. These aligned
feedforward and feedback systems develop in parallel, with SGN central axons
reaching the developing auditory brainstem around the same time that the OCN
axons extend out toward the developing inner ear. Recent findings have begun to
unravel the genetic and molecular mechanisms that guide OCN development, from
their origins in a generic pool of motor neuron precursors to their specialized
roles as modulators of cochlear activity. One recurrent theme is the importance
of efferent-afferent interactions, as afferent SGNs guide OCNs to their final
locations within the sensory epithelium, and efferent OCNs shape the activity of
the developing auditory system. This article is categorized under: Nervous System
Development > Vertebrates: Regional Development.
PMID- 29944791
TI - A health promotion project to reduce unintenti.onal injuries in and around the
home.
AB - This paper reports a health visitor-led health promotion initiative in a deprived
inner-London community to reduce unintentional injuries in and around the home.
Sessions were held in a children's centre: photography and participative theatre
techniques were used to raise parental awareness of risks to children in the
home, and to engage those attending in discussion and problem-solving. Mothers of
Bangladeshi heritage attended, and sessions were co-facilitated by a Sylheti-
speaking nursery nurse. Mothers were willing and able to participate and
expressed enthusiasm about the project. They reported a raised awareness of
dangers to children in the home, and a greater understanding of the limits to
children's own abilities to assess risk realistically. Some behaviour change was
reported. Mothers were also enthusiastic about the opportunity the sessions
provided to meet each other and to discuss more general issues of health,
including their own. The project offers a model of good practice creating a
template using the arts, which focuses on a variety of health issues and engages
the community.
PMID- 29944792
TI - Understanding SCPHN students' experience of practice educator-led peer support
groups.
AB - Specialist community public health nursing (SCPHN) students are expected to
develop significant skills and competencies in practice, whilst also achieving
academic success. This workload can be very stressful for students, particularly
as their placements with practice educators can isolate them from other students,
reducing the valuable support that peers can provide. Practice educator-led peer
support groups were established in an attempt to ameliorate student stress and
improve wellbeing by providing peer support, whilst simultaneously delivering
opportunities for learning and promoting preparedness for qualification. A
service evaluation was subsequently conducted using focus group methodology to
explore students' experience of the peer support groups. This was to ascertain
their effectiveness in supporting learning within practice placements and
improving student wellbeing. Data analysis identified three key themes: peer
support and emotional nourishment; and filling the theory-practice gap; with a
further theme focusing on group organisation and planning. Findings indicated
that the support groups were a valued and important element of SCPHN training for
the student cohort involved in this service evaluation, engendering an improved
sense of wellbeing and an enhanced educational experience.
PMID- 29944793
TI - "A lucky man".
PMID- 29944794
TI - Anatomy of an Acquisition Alternative: Leasing the Practice.
AB - The default position of many healthcare systems seeking physician alignment is to
acquire the practice and employ the physicians, but there is another approach
that poses far less firancial risk to both parties and is far easier to undo if
necessary: leasing the practice. The group stays as it is, but renders services
for which the hospital receives the reimbursement and commits to paying the group
a fixed amount for a stable quantum of work. Additional alignment features can be
added, including medical directorships, comanagement, quality bonuses, and more.
Potential problem areas include post-termination restrictive covenants and
dispute resolution. Planning in advance for both fair market value disputes and
addition of new practitioners is useful.
PMID- 29944795
TI - The Relationship Between Work Relative Value Unit Awareness and Work Relative
Value Unit Accumulation Among Physicians.
AB - This was a retrospective, cross-sectional study to determine whether a
relationship exists between work relative value unit(wRVU) awareness and wRVU
accumulation among faculty physicians. Physician wRVU awareness was obtained by a
distributed survey to faculty physicians in early 2016. wRVU accumulation was
pulled from a faculty productivity database. Productivity data from FY14-FY15 was
used to determine wRVU accumulation relative to each respondent's specialty
specific benchmark. Data were analyzed to investigate the nature, of the
relationship between awareness and accumulation. The analysis showed that
physicians with above-average awareness were significantly more likely to surpass
their wRVU benchmark when compared to physicians with below-average awareness.
Additionally, wRVU awareness accounted for a significant percentage of the
variation in wRVU output. Considering the financial importance of wRVU generation
for healthcare organizations, there is a need to devote more time and resources
to developing physician awareness of wRVUs.
PMID- 29944797
TI - Employee Absences and the Americans with Disabilities Act.
AB - Under the Americans with Disabilities Act (ADA), a leave of absence may be a
reasonable accommodation if it is likely to enable the employee to return to
work. Employers should review their attendance and disciplinary policies to
ensure that they are not violating the ADA when enforcing these policies. When an
employee requests time off, the employer should determine the employee's rights
under all of the relevant statutes if the request is related or possibly related
to a disability. Importantly, the ADA is not a free pass for violations of an
employer's attendance policy. Employers are within their rights to require
doctor's note or other documentation to substantiate an employee's need for
leave.
PMID- 29944796
TI - An Assessment of Three Post-Discharge Drug-Based Quality Assurance Events for
Elderly Medicare Beneficiaries Enrolled in a Stand-Alone Part D Plan.
AB - This article examines the distribution of drug-based quality assurance events
(QAEs) post-discharge across five-day increments and identifies characteristics
associated with post-discharge QAEs. Data were obtained through a cross-sectional
study of Medicare beneficiaries age 65 and over enrolled in stand-alone Part D
plans during calendar year 2010. Our findings suggest an even more compressed
timeframe than previously identified in the literature for addressing medication
issues among elderly beneficiaries. Specifically, medication reconciliation is
needed within two to three days of discharge instead of within 14 days as the
literature suggests. To decrease inadvertent readmissions, an immediate in
community medication reconciliation following hospital discharge is needed.
PMID- 29944798
TI - The Patient-Centered Medical Home: Part IlIl: Time to Play Ball!
AB - The Patient-Centered Medical Home (PCMH) represents a shift in how health-care is
delivered as it shifts from reactive to proactive. A care transformation model
with a number of studies demonstrating its effectiveness, PCMH can be a
significant undertaking for primary care practices. This article presents a
general overview of the PCMH model and briefly explains how it relates to the
other healthcare reforms taking place.
PMID- 29944799
TI - Developing Skills that Turn Physicians into Strong Leaders in a Rapidly Changing
Healthcare Environment.
PMID- 29944801
TI - Mow to Assess, Recognize, and Reward Teamwork.
AB - Although meaicai practice managers often know a lot about how to reward
individual employee performance, they may not be as well versed in the best
strategies for rewarding teamwork. However, the most effective employee
recognition and rewards programs focus on both individual and team performance.
This article describes strategies that practice managers can use to reward
teamwork without lessening their employees' desire to perform well individually.
It describes five possible goals for a team rewards program and 10 practical tips
for assessing and rewarding teamwork. This article also identifies three common
concerns about rewarding teamwork and strategies for overcoming those concerns.
It describes three types of team rewards programs and discusses when to use
continuous and intermittent rewards. This article also offers medical practice
managers a reliable five-question survey to use with their employees to assess
teamwork and suggests a strategy to encourage employees to recognize the teamwork
they observe in one another. Finally, this article explores the importance of the
medical practice manager's attitude about team recognition and rewards and
suggests what to do when the manager is conflicted about the team rewards he or
she must give.
PMID- 29944800
TI - Productivity Improvement: Three Steps to Move from 25% to 90% Productivity.
AB - The term productivity, as used in the practice ot medicine, reters to a
measurement of physician output over a specified period of time. Output can be a
measure of such things as dollars generated or collected or the number of patient
encounters, studies conducted, or procedures performed. A challenge faced when
attempting to use gross or net income or volume of patients as measures of
productivity is that the productivity measures of equally productive physicians
will differ based on payer and patient mixes and on the complexity of the
services rendered. This article discusses the use of the relative value unit as a
metric of productivity and how the use of this metric levels the playing field.
PMID- 29944802
TI - Creating a Standardized Operating Room Management Curriculum for Anesthesia
Trainees.
AB - As the healthcare environment evolves, physicians are taking on new roles and
responsibilities. In addition to clinical care, physicians must now be
knowledgeable about administrative concepts and understand healthcare finances.
However, these nonclinical subjects usually are not taught during residency
training. Introducing these topics into all residencies in the form of
standardized lectures, reading materials, and management rotations is a way to
bridge the knowledge gap and better prepare future physicians as they enter the
workforce. Currently, very few programs have a curriculum that addresses the
required elements. Implementing a specific operating room management curriculum
will, ideally, allow residents to gain practica and theoretical experience in
this area and develop a better understanding of the scope of administrative
medicine.
PMID- 29944803
TI - A Sampling of Alternative Payment Models.
AB - Understanding the current selection of CMS-approved alternative payment models is
critical for providers in the current healthcare policy climate who wish to
pursue alternatives to traditional reimbursement schemes. This has become a topic
of increasing interest with the recent passage of the Medicare Access and CHIP
Reauthorization Act of 2015, as traditional fee-for-service payments will be
altered-either positively or negatively-by criteria defined under the Merit-Based
Incentive Payment System (MIPS). This article offers a framework for current and
proposed models being implemented or investigated by the CMS. Further exploration
of the topic can be carried out through supplementary or primary sources to
determine best fits for specific practice environments.
PMID- 29944804
TI - Putting the Patient in "Patient-Centric".
AB - Patient care has changed over the years, primarily due to insurance issues and
changes. Practices should go back to improving patient care by putting patients
and their preferences and needs first. Scheduling an appointment should be an
easy process for the patient. Wait times should be decreased, both for getting in
to see the physician and while at the appointment. Training of staff to better
accommodate the patient should be a priority. Patients need to feel good about
your practice.
PMID- 29944805
TI - Why Patients Sue Physicians: Risk Management Strategies.
AB - Physicians may head off allegations of negligence by developing a comprehensive
understanding of why patients sue physicians and by appreciating what activities
commonly lead to patient injury. With this knowledge, physicians can develop risk
management strategies to reduce the likelihood of being named in a negligence
lawsuit. We outline the common reasons why patients sue physicians, and what
activities frequently lead to patient harm. The case examples emphasize the
factors that can lead to allegations of negligence and patient harm.
PMID- 29944807
TI - The False Claims Act: Increases in Investigations, Violations, and Penalties.
AB - The False Claims Act is a tool used by the government, its contractors, and even
employees of healthcare providers to recover overpayments and other improper
reimbursements given to physicians for healthcare services provided to Medicare
and other federal health program beneficiaries. In recent years, we have seen an
increase in the number of False Claims Act cases filed against unsuspecting
healthcare providers and practices. These cases have resulted in billions of
dollars being paid back to the federal government. Knowing and understanding the
requirements of the False Claims Act and implementing best practices and
strategies to avoid violating any of these provisions will help practices to
ensure that they do not become subject to the massive penalties imposed on
violators.
PMID- 29944806
TI - The Economic Role of Physicians in Today's Evolving Healthcare System.
AB - Physicians provide millions of patients with essential medical care each year on
which a dollar value cannot be placed. However, the economic role physicians play
in healthcare delivery can be calibrated. According to a new Merritt Hawkins
survey indicating net annual revenue generated by physicians for their affiliated
hospitals, and according to data indicating the economic contributions physicians
make to their communities, this role remains highly significant. Even as payment
models transition from volume-based metrics to value-based metrics, the economic
role of physicians in healthcare will remain pivotal.
PMID- 29944808
TI - A Roadmap for Strategic Planning in the Healthcare Practice.
AB - The days of a practice putting up a shingle or sign and waiting for patients to
come for treatment are over. The same applies to hospitals, which can't just have
beds, an emergency department, an operating room, and an intensive care unit and
hope to remain profitable in this tumultuous era of healthcare delivery. Now it
is imperative to have a strategic plan to move forward. Practices and hospitals
need a plan in order to prosper, rather than settle for mere survival. This
article defines strategic planning, discusses the creation of a strategic plan,
and lays out how a plan might be implemented in a medical practice or hospital.
PMID- 29944809
TI - Ten Pearls on Starting an RN Care Management Program in Your Practice.
AB - Care management targets the most medically compiex patients in a practice in an
attempt to reduce hospitalizations and improve health outcomes for those
patients. Care management and care coordination have been shown to reduce costs
to the healthcare system and are increasingly seen in practices following the
patient-centered medical home model. This article defines 10 lessons we have
learned over the last four years as we integrated RN-driven care management in
our practice.
PMID- 29944810
TI - Doctor, Please Take the Stand: Stress, Duties, and Dangers of Physician
Testimony.
AB - Many physicians experience stress and anxiety when they are asked to testify in
court or be an expert witness. Handling a barrage of attorney questions under
oath can be challenging. And although testifying against a patient who has sued
for malpractice is, of course, difficult, testifying against a colleague-for
example, in an impairment or patient safety case-can be even worse. This article
addresses some of the key reasons that cause physicians to resist testifying, and
suggests ways for physicians to deliver their testimony in a way that is
effective and can be understood by a jury.
PMID- 29944811
TI - A Retrospective Analysis of a Consolidation of Urology Practices, and the
Resulting Physician Productivity in the Provision of Urologic Care.
AB - In recent decades, the number of small medical practices has decreased, allowing
for larger conglomerates to form. Although the literature includes several
studies looking at physician productivity in small practices as opposed to larger
groups, almost none have been performed in recent years. This study looks at a
consolidated urology practice that has combined many physicians from many smaller
groups, and how it is performing in terms of physician productivity. Productivity
measures from each physician's initial years in the larger practice were
analyzed, demonstrating that the physicians in the larger practice become
significantly more productive during their time in the practice. This
productivity can be attributed to a variety of factors, including strong
physician leadership, a superior management team, a steadfast support staff, and
well-equipped facilities.
PMID- 29944812
TI - The Components of the Merit-Based Incentive Payment System.
AB - The passage of the Medicare Access and CHIP Reauthorization Act in Apri 2015 set
the stage for the Part B reimbursement changes set to take place in 2019 based on
the 2017 reporting period in relation to performance within core Medicare
initiatives through the Merit-Based Incentive Payment System (MIPS) These changes
will reflect the new "fee-for-performance" approach to reimbursements through
individualized changes to an individual or practice group's conversion factor
used in the RVU reimbursement calculation. The metrics being used as a basis for
eligible provider competitive ranking for either positive or negative
reimbursement changes are in proportion to performance on chosen Physician
Quality Reporting System measures, value-based payment modifier calculations,
compliance with Modified Stage 2 or Stage 3 Meaningful Use as part of the
Electronic Health Record Incentive Program, and ongoing participation in clinical
practice improvement activities. This article describes the core elements that
make up MIPS and discusses the likely criteria that will be used as the core
elements necessary for competitive reimbursement rankinq.
PMID- 29944813
TI - Malpractice Considerations: New Concerns on the Horizon.
AB - Physicians practicing medicine in today's ever-shifting and advancing medical
world are at risk for malpractice liability. The introduction of a vast array of
telecommunication media into the physician world is creating a growing area of
malpractice risk for physicians. This article explores the new malpractice
considerations facing physicians in our constantly evolving digital world.
Although they are novel and just on the horizon, these risks are real, and it is
prudent for every practicing physician to consider them carefully.
PMID- 29944814
TI - Do You Really Know What I Do?
AB - A practice manager wears many hats. He or she is responsible for the smooth
running of the practice and all that that entails. Practice managers often come
in early, stay late, and are involved in all aspects of running the practice. The
question is, does the physician realize how much his or her manager does and how
valuable the manager is? As a practice manager, it is important to meet with the
physician, share ideas, and discuss the revenue and profits to ensure a
successful practice.
PMID- 29944815
TI - How Does Your Practice Measure Up? Insights from Benchmarking Medicare Payments.
AB - Physician practices have historically had difficulty benchmarking their services
because there are limits to the transfer of payment information among healthcare
providers. Using standard analysis tools (e.g., Microsoft Excel) and data from
CMS, we outline and provide a detailed example of how a physician practice can
benchmark one revenue stream within its local geographic market. The data cover
patients serviced under original Medicare from 2012 to 2014. In today's
healthcare environment, with changing payment methodologies, understanding the
revenue streams for a physician practice is essential to a practice's overall
financial health.
PMID- 29944816
TI - Overpayments and Voluntary Repayments Under the New 60-Day Rule.
AB - In 2010, with the passage of the Affordable Care Act, Congress created an
obligation for healthcare providers to return overpayments that they receive
within 60 days, or risk False Claims Act exposure. This year, CMS finally
published regulations that clarify this statutory language. The regulations,
however, impose strict standards on healthcare providers, wherein constructive
knowledge can be imputed to a healthcare provider if that provider failed to
exercise reasonable diligence. This article explores the new regulations,
examines the practical implications of these new standards, and discusses the
risks providers may face if they fail to engage in ongoing compliance efforts.
PMID- 29944817
TI - The Affordable Care Act and Digital Health Applications.
AB - Telehealth, the delivery of health-related services and information via digital
communication technologies, is a rapidly emerging, innovative, cost-effective and
efficient way to deliver healthcare. There are three main types of telehealth:
store and forward; remote monitoring; and real-time interactive services.
Smartphone applications, or apps, that connect a provider with a patient, known
as "connective health apps," fall under this umbrella of telehealth and can
function in all three of the categories. As the Affordable Care Act legislates to
improve quality, lower costs, and expand coverage, connective health apps are an
important aspect of the Act. This article addresses to what extent the Affordable
Care Act and private insurers cover and promote connective health apps and
discusses the potential limitations and benefits of these apps and the best ways
to integrate them in the future.
PMID- 29944818
TI - The Art of the Morning Huddle: How to Use This Simple Tool to Build Your Team.
AB - A well-planned and focused daily huddle meeting with your employees can greatly
impact your medical practice team's ability to work cohesively, create a seamless
flow, increase efficiency, reduce stress, and provide exceptional patient care.
This article explores these and other benefits of morning huddles, including how
medical practice managers can use morning huddles to build and foster team
morale. It offers 12 practical tips for creating and using morning huddles,
including a sample huddle agenda and recommended logistics for holding a huddle
meeting. It also describes nine benefits of morning huddles and four practice
management goals for huddles. Finally, this article also offers eight fun ideas
to keep morning huddles interesting and three strategies for getting team buy-in
for morning huddles.
PMID- 29944819
TI - Proactively Prepare for MIPS Now-Your Future Self Will Thank You.
AB - The message is clear-the Medicare Access and CHIP Reauthorization Act of 2015
represents a complete paradigm shift in our healthcare system, and its
implementation will span several years. Consider it the shift from paying doctors
using a traditional fee-for-service reimbursement model to one that pays
according to the value that they provide to their patients, where "value" is
defined by participation in several health IT and quality reporting programs. For
many providers, this shift in thinking and their way of practicing medicine will
be one of the greatest challenges of their career. The best thing you can do is
to proactively prepare for the Merit-Based Incentive Payment System now. Your
future self will thank you.
PMID- 29944820
TI - The Conundrum of Medical Licensure for Physician Leaders.
AB - This article discusses the dichotomy between the need for physician leaders and
the need for alternative pathways for medical licensure for nonpracticing
physicians who seek leadership roles, including the possibility of a national
solution to the problem. Currently, no nationwide licensing standards or
requirements exist for clinically inactive physician leaders, and states have
different requirements and procedures for licensure. In many states, physician
leaders who no longer practice medicine may be held to the same standards of
medical licensure as practicing physicians, which may require board
recertification or enrollment in formal "reentry" programs and other activities
that may seem unreasonable or irrelevant to the roles and responsibilities of
physicians in leadership positions. Physicians interested in leaving practice for
leadership opportunities in industry and other sectors of medicine should always
maintain an active medical license. Those seeking employment in a state other
than the one(s) in which they are currently licensed should not make any job
commitments based on expectation of licensure until they are actually licensed.
PMID- 29944821
TI - The Role of Technology in the Small Medical Office.
AB - Just a few years ago, the advances in technology in the medical office were the
electronic medical record, a website, and electronic prescription writing. Today
those are necessary requirements for any medical practice, regardless of size.
Most large practices now have patient portals, e-mail reminders and e-mail
newsletters, and automated patient appointment reminders. Now small practices
also can have access to affordable technology that improves the efficiency and
productivity of the office practice and also helps patients live healthier lives.
The advances in technology could help save money in healthcare costs and improve
patient treatment. This article discusses technology that is helpful for small
practices and that can be implemented into a practice easily and inexpensively
without the assistance or employment of IT specialists.
PMID- 29944823
TI - Imaging of Lipids in Native Human Bone Sections Using TOF-Secondary Ion Mass
Spectrometry, Atmospheric Pressure Scanning Microprobe Matrix-Assisted Laser
Desorption/Ionization Orbitrap Mass Spectrometry, and Orbitrap-Secondary Ion Mass
Spectrometry.
AB - A method is described for high-resolution label-free molecular imaging of human
bone tissue. To preserve the lipid content and the heterogeneous structure of
osseous tissue, 4 MUm thick human bone sections were prepared via cryoembedding
and tape-assisted cryosectioning, circumventing the application of organic
solvents and a decalcification step. A protocol for comparative mass spectrometry
imaging (MSI) on the same section was established for initial analysis with time
of-flight secondary ion mass spectrometry (TOF-SIMS) at a lateral resolution of
10 MUm to <500 nm, followed by atmospheric pressure scanning microprobe matrix
assisted laser desorption/ionization (AP-SMALDI) Orbitrap MSI at a lateral
resolution of 10 MUm. This procedure ultimately enabled MSI of lipids, providing
the lateral localization of major lipid classes such as glycero-, glycerophospho
, and sphingolipids. Additionally, the applicability of the recently emerged
Orbitrap-TOF-SIMS hybrid system was exemplarily examined and compared to the
before-mentioned MSI methods.
PMID- 29944822
TI - Crystal Structure of Apo MEF2B Reveals New Insights in DNA Binding and Cofactor
Interaction.
AB - The myocyte enhancer factor 2 (MEF2) family of transcription factors plays
important roles in developmental processes and adaptive responses. Although MEF2
proteins are known to bind DNA in the nucleus to regulate specific gene
expression, there are reports that show that MEF2 also functions in the
cytoplasm. Previous structural studies of MEF2 focused exclusively on DNA-bound
MEF2 with and without various corepressors or coactivators. While these studies
have established a comprehensive structural model of DNA recognition and cofactor
recruitment by MEF2, the structure of MEF2 not bound to DNA, which include
cytoplasmic MEF2 and free MEF2 in the nucleus, is unknown. Here we determined the
structure of the MADS-box/MEF2 domain of MEF2B without DNA nor cofactor. The Apo
structure of MEF2B reveals a largely preformed DNA binding interface that may be
important for recognizing the shape of DNA from the minor groove side. In
addition, our structure also reveals that the C-terminal helix of the MEF2
specific domain could flip up to bind to the hydrophobic groove that serves as
the binding sites of MEF2 transcription cofactors. These observations shed new
insights into DNA binding and cofactor interaction by MEF2 proteins.
PMID- 29944824
TI - Nanoscale Electrical Degradation of Silicon-Carbon Composite Anode Materials for
Lithium-Ion Batteries.
AB - High-performance lithium-ion batteries (LIBs) are in increasing demand for a
variety of applications in rapidly growing energy-related fields including
electric vehicles. To develop high-performance LIBs, it is necessary to
comprehensively understand the degradation mechanism of the LIB electrodes. From
this viewpoint, it is crucial to investigate how the electrical properties of LIB
electrodes change under charging and discharging. Here, we probe the local
electrical properties of LIB electrodes with nanoscale resolution by scanning
spreading resistance microscopy (SSRM). Via quantitative and comparative SSRM
measurements on pristine and degraded LIB anodes of Si-C composites blended with
graphite (Gr) particles, the electrical degradation of the LIB anodes is
visualized. The electrical conductivity of the Si-C composite particles
considerably degraded over 300 cycles of charging and discharging, whereas the Gr
particles maintained their conductivity.
PMID- 29944825
TI - Green Chemistry in Red Emulsion: Interface of Dye Stabilized Emulsions as a
Powerful Platform for the Formation of sub-20-nm SiO2 Nanoparticles.
AB - Dye stabilized nanoemulsions offer the unique possibility of creating both silica
capsules and sub-20-nm particles with precise control of particle size and narrow
dispersity from the same system by the choice of the proper dye. The large o/w
interface enhances the kinetics of particle formation significantly over
macroscopic interfaces which enables the synthesis of silica nanoparticles
without any catalyst or elevated temperatures under static conditions. This is in
contrast to syntheses for sub-20-nm silica nanoparticles described until now
which can normally not be conducted at neutral pH and/or room temperature without
stirring. Furthermore, the synthesis can be run without any additional organic
solvent and the dyes can be easily removed from the dispersion which opens the
pathway to silica dispersions containing only particles, traces of ethanol and
water at neutral pH without centrifugation, washing, or redispersion in
accordance with the idea of "green chemistry".
PMID- 29944826
TI - Aligned Carbon Nanotube Synaptic Transistors for Large-Scale Neuromorphic
Computing.
AB - This paper presents aligned carbon nanotube (CNT) synaptic transistors for large
scale neuromorphic computing systems. The synaptic behavior of these devices is
achieved via charge-trapping effects, commonly observed in carbon-based
nanoelectronics. In this work, charge trapping in the high- k dielectric layer of
top-gated CNT field-effect transistors (FETs) enables the gradual analog
programmability of the CNT channel conductance with a large dynamic range ( i.
e., large on/off ratio). Aligned CNT synaptic devices present significant
improvements over conventional memristor technologies ( e. g., RRAM), which
suffer from abrupt transitions in the conductance modulation and/or a small
dynamic range. Here, we demonstrate exceptional uniformity of aligned CNT FET
synaptic behavior, as well as significant robustness and nonvolatility via pulsed
experiments, establishing their suitability for neural network implementations.
Additionally, this technology is based on a wafer-level technique for
constructing highly aligned arrays of CNTs with high semiconducting purity and is
fully CMOS compatible, ensuring the practicality of large-scale CNT+CMOS
neuromorphic systems. We also demonstrate fine-tunability of the aligned CNT
synaptic behavior and discuss its application to adaptive online learning schemes
and to homeostatic regulation of artificial neuron firing rates. We simulate the
implementation of unsupervised learning for pattern recognition using a spike
timing-dependent-plasticity scheme, indicate system-level performance (as
indicated by the recognition accuracy), and demonstrate improvements in the
learning rate resulting from tuning the synaptic characteristics of aligned CNT
devices.
PMID- 29944827
TI - DBU-Catalyzed Alkyne-Imidate Cyclization toward 1-Alkoxypyrazino[1,2- a]indole
Synthesis.
AB - 1-(Propargyl)indol-2-carbonitriles react with alcohols to afford 1
alkoxypyrazino[1,2- a]indoles under DBU-catalyzed microwave-assisted conditions.
The reaction scope includes a wide range of indoles, primary and secondary
alcohols, and a thiol. The initial mechanistic study shows that the domino
process presumably proceeds through an alkyne-allene rearrangement, imidate
formation, and nucleophilic cyclization reaction sequence.
PMID- 29944828
TI - From PCBM-Polymer to Low-Cost and Thermally Stable C60/C70-Polymer Solar Cells:
The Role of Molecular Structure, Crystallinity, and Morphology Control.
AB - The adoption of neat-fullerene (C60 and C70) in polymer solar cells offers
opportunities to develop cost-effective and thermally stable devices. Here,
through rational side-chain engineering of low optical-gap polymer
poly(benzodithiophene-furan-diketopyrrolopyrrole)s (PBDs), we demonstrated for
the first time a polymer/C70 blend exhibited higher efficiency (best 6.1%)
compare to their polymer/[70]PCBM (best 5.7%) counterparts, and the best
efficiency is at the front of efficient polymer/neat-fullerene solar cells. More
importantly, we first demonstrated the morphology optimization methodology for
solution-processed polymer/neat-fullerene blends in order to reduce the strong
crystallization and aggregation of neat-fullerene molecules. In comparison with
previous work, these results can provide not only material design strategy but
also fundamental difference between polymer/neat-fullerene and polymer/PCBM blend
morphology, which allow us better understanding of how to choose proper materials
and optimize blend morphology in polymer/neat-fullerene based device to deliver
higher photovoltaic performance.
PMID- 29944829
TI - Ferroelectric Field-Effect Transistors Based on MoS2 and CuInP2S6 Two-Dimensional
van der Waals Heterostructure.
AB - We demonstrate room-temperature ferroelectric field-effect transistors (Fe-FETs)
with MoS2 and CuInP2S6 two-dimensional (2D) van der Waals heterostructure. The
ferroelectric CuInP2S6 is a 2D ferroelectric insulator, integrated on top of MoS2
channel providing a 2D/2D semiconductor/insulator interface without dangling
bonds. The MoS2- and CuInP2S6-based 2D van der Waals heterostructure Fe-FETs
exhibit a clear counterclockwise hysteresis loop in transfer characteristics,
demonstrating their ferroelectric properties. This stable nonvolatile memory
property can also be modulated by the back-gate bias of the MoS2 transistors
because of the tuning of capacitance matching between the MoS2 channel and the
ferroelectric CuInP2S6, leading to the enhancement of the on/off current ratio.
Meanwhile, the CuInP2S6 thin film also shows resistive switching characteristics
with more than four orders of on/off ratio between low- and high-resistance
states, which is also promising for resistive random-access memory applications.
PMID- 29944830
TI - Kaolinite Enhances the Stability of the Dissolvable and Undissolvable Fractions
of Biochar via Different Mechanisms.
AB - Input of biomass-derived biochar into soil is recognized as a promising method of
carbon sequestration. The long-term sequestration effect of biochar depends on
the stability of both its dissolvable and undissolvable fractions in soil, which
could be affected by their interactions with soil minerals. Here, walnut shell
derived biochar was divided into dissolvable and undissolvable fractions and then
interacted with kaolinite. Stability of kaolinite-biochar associations was
evaluated by chemical oxidation and biological degradation. At low dissolvable
biochar concentrations, the association was mainly attributed to "Ca2+ bridging"
and "ligand exchange", whereas "van der Waals attraction" was dominant at high
concentrations. For the undissolvable biochar, kaolinite raised the activation
energy of its surface by 22.1%, causing a reduction in biochar reactivity. By
chemical oxidation, kaolinite reduced the C loss of total biochar by 42.5%, 33.1%
resulting from undissolvable biochar and 9.4% from dissolvable biochar. Because
of the presence of kaolinite, the loss of biodegradable C in total biochar was
reduced by 49.4% and 48.2% from undissolvable fraction and 1.2% from dissolvable
fraction. This study indicates that kaolinite can increase the stability of both
dissolvable and undissolvable biochar, suggesting that kaolinite-rich soils could
be a beneficial environment for biochar for long-term carbon sequestration.
PMID- 29944831
TI - Nighttime Aqueous-Phase Formation of Nitrocatechols in the Atmospheric Condensed
Phase.
AB - Yellow-colored methylnitrocatechols (MNC) contribute to the total organic aerosol
mass and significantly alter absorption properties of the atmosphere. To date,
their formation mechanisms are still not understood. In this work, the intriguing
role of HNO2 (catalytic and oxidative) in the dark transformation of 3
methylcatechol (3MC) under atmospherically relevant aqueous-phase conditions is
emphasized. Three possible pathways of dark 3-methyl-5-nitrocatechol and 3-methyl
4-nitrocatechol formation, markedly dependent on reaction conditions, were
considered. In the dominant pathway, HNO2 is directly involved in the
transformation of 3MC via consecutive oxidation and conjugated addition reactions
(nonradical reaction mechanism). The two-step nitration dominates at a pH around
the p Ka of HNO2, which is typical for atmospheric aerosols, and is moderately
dependent on temperature. Under very acidic conditions, the other two nitration
pathways, oxidative aromatic nitration (electrophilic) and recombination of
radical species, gain in importance. The predicted atmospheric lifetime of 3MC
according to the dominant mechanism at these conditions (2.4 days at pH 4.5 and
25 degrees C) is more than 3-times shorter than that via the other two
competitive pathways. Our results highlight the significance of a catechol
oxidation-conjugated addition reaction in a nighttime secondary nitroaromatic
chromophore formation in the atmosphere, especially in polluted environments with
high NO x concentrations and relatively acidic particles (pH around 3).
PMID- 29944832
TI - Construction, Model-Based Analysis, and Characterization of a Promoter Library
for Fine-Tuned Gene Expression in Bacillus subtilis.
AB - Promoters are among the most-important and most-basic tools for the control of
metabolic pathways. However, previous research mainly focused on the screening
and characterization of some native promoters in Bacillus subtilis. To develop a
broadly applicable promoter system for this important platform organism, we
created a de novo synthetic promoter library (SPL) based on consensus sequences
by analyzing the microarray transcriptome data of B. subtilis 168. A total of 214
potential promoters spanning a gradient of strengths was isolated and
characterized by a green fluorescence assay. Among these, a detailed intensity
analysis was conducted on nine promoters with different strengths by reverse
transcription polymerase chain reaction (RT-PCR) and sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE). Furthermore, reconstructed
promoters and promoter cassettes (tandem promoter cluster) were designed via
statistical model-based analysis and tandem dual promoters, which showed strength
that was increased 1.2- and 2.77-fold compared to that of promoter P43,
respectively. Finally, the SPL was employed in the production of inosine and
acetoin by repressing and over-expressing the relevant metabolic pathways,
yielding a 700% and 44% increase relative to the respective control strains. This
is the first report of a de novo synthetic promoter library for B. subtilis,
which is independent of any native promoter. The strategy of improving and fine
tuning promoter strengths will contribute to future metabolic engineering and
synthetic biology projects in B. subtilis.
PMID- 29944834
TI - A New Precision Spectroscopy Based Method for Boltzmann Constant Determination
and Primary Thermometry.
AB - We propose a new independent thermometry method, line strength ratio thermometry
(LRT), based on optical spectroscopy measurement of the line strength intensity
ratio R between pairs of molecular transitions. Due to strong dependence of R on
kT, a given measurement uncertainty deltaR for R reflects in a small uncertainty
of kT determination. By assuming experimental uncertainties of R and T to be
those reported in literature, we foresee a k determination at the 5 ppm level,
which is better than the most precise k determination by using Doppler broadening
thermometry (DBT). In the frame of a new definition of the SI Kelvin unit, based
on k as fixed constant, once the k constant is exactly established, LRT is
proposed as a high resolution noncontact thermometry technique for absolute
temperature measurements of gas samples at the ppm level.
PMID- 29944833
TI - Rationally Designed Polycationic Carriers for Potent Polymeric siRNA-Mediated
Gene Silencing.
AB - The delivery of small interfering RNA (siRNA) remains a major hurdle for the
clinical translation of RNA interference (RNAi) therapeutics. Because of its low
valency and rigid nature, siRNA typically requires high excesses of cationic
delivery materials to package it stably and deliver it to the cytoplasm of target
cells, resulting in high toxicities and inefficient gene silencing in vivo. To
address these challenges, we pair a polymeric form of siRNA, p-shRNA, with
optimized biodegradable polycations to form stable complexes that induce far more
potent gene silencing than with siRNA complexes. Furthermore, we unveil a set of
design rules governing p-shRNA delivery, using degradable polycations containing
hydrophobic and stabilizing polyethylene glycol domains that enable both stable
condensation and efficient release inside cells. We demonstrate the therapeutic
potential of this approach by silencing the oncogene STAT3 in a well-established
B16F10 mouse melanoma model to significantly prolong survival. By blending
nucleic acid engineering and polymer design, our system provides a potentially
translatable platform for RNAi-based therapies.
PMID- 29944836
TI - Antibiotic Resistome Associated with Small-Scale Poultry Production in Rural
Ecuador.
AB - Small-scale poultry farming is common in rural communities across the developing
world. To examine the extent to which small-scale poultry farming serves as a
reservoir for resistance determinants, the resistome of fecal samples was
compared between production chickens that received antibiotics and free-ranging
household chickens that received no antibiotics from a rural village in northern
Ecuador. A qPCR array was used to quantify antibiotic resistance genes (ARGs) and
mobile genetic elements (MGEs) using 248 primer pairs; and the microbiome
structure was analyzed via 16S rRNA gene sequencing. A large number of ARGs (148)
and MGEs (29) were detected. The ARG richness in production chickens was
significantly higher than that of household chickens with an average of 15 more
genes detected ( p < 0.01). Moreover, ARGs and MGEs were much more abundant in
production chickens than in household chickens (up to a 157-fold difference).
Production chicken samples had significantly lower taxonomic diversity and were
more abundant in Gammaproteobacteria, Betaproteobacteria, and Flavobacteria. The
high abundance and diversity of ARGs and MGEs found in small-scale poultry
farming was comparable to the levels previously found in large scale animal
production, suggesting that these chickens could act as a local reservoir for
spreading ARGs into rural communities.
PMID- 29944837
TI - Spin States and Other Ligand-Field States of Aqua Complexes Revisited with
Multireference ab Initio Calculations Including Solvation Effects.
AB - High-level multireference (CASPT2, NEVPT2) calculations are reported for
transition metal aqua complexes with electronic configurations from (3d)1 to
(3d)8. We focus on the experimentally evidenced excitation energies to their
various ligand-field states, including different spin states. By employing models
accounting for both explicit and implicit solvation, we find that solvation
effect may contribute up to 0.5 eV to the excitation energies depending on the
charge of ion and character of the electronic transition. We further demonstrate
that with an adequate choice of the active space and the energetics extrapolated
to the complete basis set limit, the presently computed excitation energies are
in a good agreement with the experimental data. This allows us to conclusively
resolve significant discrepancies reported in earlier theory works [e.g., J.
Phys. Chem. C 2014 , 118 , 29196 - 29208 ]. For the benchmark set of 19 spin
forbidden and 24 spin-allowed transitions (for which experimental data are
unambiguous), we find the mean absolute error of 0.15 or 0.13 eV and the maximum
error of 0.56 or 0.42 eV for CASPT2 or NEVPT2 calculations, respectively. For the
particularly challenging sextet-quartet gap for [Fe(H2O)6]3+, we support our
interpretation by additional calculations with multireference configuration
interaction (MRCI) and coupled cluster theory up to the CCSDT(Q) level. By
underlining a rather subtle interplay between the solvation and correlation
effects, the findings of this Article are relevant not only for modeling and
interpretation of optical spectra of transition metal complexes but also in
further benchmarking of theoretical methods for the challenging problem of spin
state energetics.
PMID- 29944835
TI - Cellular Uptake of the Atypical Antipsychotic Clozapine Is a Carrier-Mediated
Process.
AB - The weak base antipsychotic clozapine is the most effective medication for
treating refractory schizophrenia. The brain-to-plasma concentration of unbound
clozapine is greater than unity, indicating transporter-mediated uptake, which
has been insufficiently studied. This is important, because it could have a
significant impact on clozapine's efficacy, drug-drug interaction, and safety
profile. A major limitation of clozapine's use is the risk of clozapine-induced
agranulocytosis/granulocytopenia (CIAG), which is a rare but severe hematological
adverse drug reaction. We first studied the uptake of clozapine into human brain
endothelial cells (hCMEC/D3). Clozapine uptake into cells was consistent with a
carrier-mediated process, which was time-dependent and saturable ( Vmax = 3299
pmol/million cells/min, Km = 35.9 MUM). The chemical inhibitors lamotrigine,
quetiapine, olanzapine, prazosin, verapamil, indatraline, and chlorpromazine
reduced the uptake of clozapine by up to 95%. This could in part explain the in
vivo interactions observed in rodents or humans for these compounds. An extensive
set of studies utilizing transporter-overexpressing cell lines and siRNA-mediated
transporter knockdown in hCMEC/D3 cells showed that clozapine was not a substrate
of OCT1 (SLC22A1), OCT3 (SLC22A3), OCTN1 (SLC22A4), OCTN2 (SLC22A5), ENT1
(SLC29A1), ENT2 (SLC29A2), and ENT4/PMAT (SLC29A4). In a recent genome-wide
analysis, the hepatic uptake transporters SLCO1B1 (OATP1B1) and SLCO1B3 (OATP1B3)
were identified as additional candidate transporters. We therefore also
investigated clozapine transport into OATP1B-transfected cells and found that
clozapine was neither a substrate nor an inhibitor of OATP1B1 and OATP1B3. In
summary, we have identified a carrier-mediated process for clozapine uptake into
brain, which may be partly responsible for clozapine's high unbound accumulation
in the brain and its drug-drug interaction profile. Cellular clozapine uptake is
independent from currently known drug transporters, and thus, molecular
identification of the clozapine transporter will help to understand clozapine's
efficacy and safety profile.
PMID- 29944840
TI - Understanding Anemia in the ICU to Develop Future Treatment Strategies.
PMID- 29944838
TI - Comprehensive Toxic Plants-Phytotoxins Database and Its Application in Assessing
Aquatic Micropollution Potential.
AB - The production of toxic plant secondary metabolites (phytotoxins) for defense is
a widespread phenomenon in the plant kingdom and is even present in agricultural
crops. These phytotoxins may have similar characteristics to anthropogenic
micropollutants in terms of persistence and toxicity. However, they are only
rarely included in environmental risk assessments, partly because a systematic
overview of phytotoxins is missing. Here, we present a newly developed, freely
available database, Toxic Plants-PhytoToxins (TPPT), containing 1586 phytotoxins
of potential ecotoxicological relevance in Central Europe linked to 844 plant
species. Our database summarizes phytotoxin patterns in plant species and
provides detailed biological and chemical information as well as in silico
estimated properties. Using the database, we evaluated phytotoxins regarding
occurrence, approximated from the frequencies of Swiss plant species;
environmental behavior based on aquatic persistence and mobility; and toxicity.
The assessment showed that over 34% of all phytotoxins are potential aquatic
micropollutants and should be included in environmental investigations.
PMID- 29944839
TI - iBioSim 3: A Tool for Model-Based Genetic Circuit Design.
AB - The iBioSim tool has been developed to facilitate the design of genetic circuits
via a model-based design strategy. This paper illustrates the new features
incorporated into the tool for DNA circuit design, design analysis, and design
synthesis, all of which can be used in a workflow for the systematic construction
of new genetic circuits.
PMID- 29944841
TI - Renewed Promise of Nonionizing Radiation Imaging for Chronic Lung Disease in
Preterm Infants.
PMID- 29944843
TI - The Light at the End of the Long Pulmonary Hypertension Tunnel Brightens.
PMID- 29944842
TI - Early Pulmonary Vascular Disease in Young Adults Born Preterm.
AB - RATIONALE: Premature birth affects 10% of live births in the United States, and
is associated with alveolar simplification and altered pulmonary microvascular
development. However, little is known about the long-term impact prematurity has
on the pulmonary vasculature. OBJECTIVE: Determine the long-term effects of
prematurity on right ventricular and pulmonary vascular hemodynamics. METHODS:
Preterm subjects (n=11) were recruited from the Newborn Lung Project, a
prospectively followed cohort at the University of Wisconsin-Madison, born
preterm with very low birth weight (<=1500g; average gestational age 28 weeks)
between 1988 and 1991. Control subjects (n=10) from the same birth years were
recruited from the general population. All subjects had no known adult
cardiopulmonary disease. Right heart catheterization was performed to assess
right ventricular and pulmonary vascular hemodynamics at rest and during hypoxic
and exercise stress. RESULTS: Preterm subjects had higher mean pulmonary arterial
pressures (mPAP), with 27% (3/11) meeting criteria for borderline pulmonary
hypertension (mPAP 19-24 mmHg) and 18% (2/11) meeting criteria for overt
pulmonary hypertension (mPAP >=25 mmHg). Pulmonary vascular resistance and
elastance were higher at rest and during exercise, suggesting a stiffer vascular
bed. Preterm subjects were significantly less able to augment cardiac index or
right ventricular stroke work during exercise. Among neonatal characteristics,
total ventilatory support days was the strongest predictor of adult pulmonary
pressure. CONCLUSION: Young adults born preterm demonstrate early pulmonary
vascular disease, characterized by elevated pulmonary pressures, a stiffer
pulmonary vascular bed, and right ventricular dysfunction, consistent with an
increased risk of developing pulmonary hypertension.
PMID- 29944844
TI - Reply to Voelkel and Newman: The Light at the End of the Long Pulmonary
Hypertension Tunnel Brightens.
PMID- 29944845
TI - Cardiac autonomic function during hypothermia and its measurement repeatability.
AB - This study examined the effect of mild hypothermia (a 0.5 degrees C decrease in
rectal temperature) on heart rate variability (HRV), with the identical
hypothermia protocol performed twice and compared using intraclass correlation
coefficient (r) analysis to study the repeatability. Twelve healthy males each
completed a Neutral (23 degrees C) and two Cold (0 degrees C) trials. In the
Neutral trial participants sat quietly for 30 min. In the Cold trials, baseline
data were obtained from a 5-min sample following 30 min of quiet sitting at 23
degrees C, followed by passive exposure to 0 degrees C; hypothermic measures were
taken from a 5-min period immediately prior to rectal temperature decreasing by
0.5 degrees C. HRV was obtained from a three-lead ECG. There were no differences
(all p>0.05) in baseline measures between the Neutral and the two Cold trials,
suggesting no pre-cooling anxiety related to the Cold trials. Heart rate along
with HRV measures RMSSD, TINN, LF, and HF increased (all p<0.05) with mild
hypothermia and showed excellent reliability between the two Cold trials (all
r>=0.81). In contrast, HF/LF ratio decreased (p<0.05) and had only fair
reliability between the two Cold trials (r=0.551). In general, hypothermia led to
increases in heart rate along with most measures of HRV. While counter-intuitive
that both sympathetic and vagal influence would increase simultaneously, these
changes likely reflect increased stress from whole body cooling along with marked
cardiovascular strain and sympathetic nervous system activity from shivering to
defend core body temperature. An important methodological consideration for
future studies is the consistent and repeatable HRV responses to hypothermia.
PMID- 29944846
TI - Letter to the Editor: Choroidal Thickness in Diabetic Macular Edema Compared to
Normal Controls.
PMID- 29944847
TI - Effect of food intake on the ventilatory response to increasing core temperature
during exercise.
AB - Food intake increases metabolism and body temperature, which may in turn
influence ventilatory responses. Our aim was to assess the effect of food intake
on ventilatory sensitivity to rising core temperature during exercise. Nine
healthy male subjects exercised on a cycle ergometer at 50% of peak oxygen uptake
in sessions with and without prior food intake. Ventilatory sensitivity to rising
core temperature was defined by the slopes of regression lines relating
ventilatory parameters to core temperature. Mean skin temperature, mean body
temperature (calculated from esophageal temperature and mean skin temperature),
oxygen uptake, carbon dioxide elimination, minute ventilation, alveolar
ventilation, and tidal volume (VT) were all significantly higher at baseline in
sessions with food intake than without food intake. During exercise, esophageal
temperature, mean skin temperature, mean body temperature, carbon dioxide
elimination, and end-tidal CO2 pressure were all significantly higher in sessions
with food intake than without it. By contrast, ventilatory parameters did not
differ between sessions with and without food intake, with the exception of VT
during the first 5 min of exercise. The ventilatory sensitivities to rising core
temperature also did not differ, with the exception of an early transient effect
on VT. Food intake increases body temperature before and during exercise. Other
than during the first 5 min of exercise, food intake does not affect ventilatory
parameters during exercise, despite elevation of both body temperature and
metabolism. Thus, with the exception of an early transient effect on VT,
ventilatory sensitivity to rising core temperature is not affected by food
intake.
PMID- 29944848
TI - Exercise biology of neuromuscular disorders.
AB - Neuromuscular disorders (NMDs) are chronic conditions that affect the
neuromuscular system. Many NMDs currently have no cure; however, as more
effective therapies become available for NMD patients, these individuals will
exhibit improved health and/or prolonged lifespans. As a result, persons with
NMDs will likely desire to engage in a more diverse variety of activities of
daily living, including increased physical activity or exercise. Therefore, there
is a need to increase our knowledge of the effects of acute exercise and chronic
training on the neuromuscular system in NMD contexts. Here, we discuss the
disease mechanisms and exercise biology of Duchenne muscular dystrophy (DMD),
spinal muscular atrophy (SMA), and myotonic dystrophy type 1 (DM1), which are
among the most prevalent NMDs in children and adults. Evidence from clinical and
preclinical studies are reviewed, with emphasis on the functional outcomes of
exercise, as well as on the putative cellular mechanisms that drive exercise
induced remodelling of the neuromuscular system. Continued investigation of the
molecular mechanisms of exercise adaptation in DMD, SMA, and DM1 will assist in
enhancing our understanding of the biology of these most prevalent NMDs. This
information may also be useful for guiding the development of novel therapeutic
targets for future pursuit.
PMID- 29944849
TI - When the whole is equal to the sum of its parts: A new approach to study face and
body perception and representation.
AB - In this paper, a new approach and a novel method to study face perception is
proposed and tested using several qualitative experiments. This method is based
on three main tasks: a description task (subjects were asked to freely describe
the target stimulus), a free pictorial task (free drawing/painting of what
subjects were asked), and a pictorial reproduction task (making a copy of what
subjects perceived). These tasks were carried out with children and adults and
extended to conditions related to visual arts. The starting points of this work
were the canonical perspective and the holistic processes involved in face
perception. The aim of this work was to answer the two following basic questions:
Are canonical perspective and holistic processes really effective for face
perception? Is face perception other than the sum of its parts? The outcomes of
the experiments clearly refuted the role of canonical perspective and weaken the
holistic approach to face and body perception. The whole human body has been
shown instead to appear as if built starting from every single component,
therefore body and faces are like wholes, decomposable in a mosaic of juxtaposed
independent components reduced to a reference image. In short, the whole is equal
to the sum of its parts. Finally, our results also show evidence supporting the
introduction of the notion of icon.
PMID- 29944850
TI - Intravitreal administration of endothelin type A receptor or endothelin type B
receptor antagonists attenuates hypertensive and diabetic retinopathy in rats.
AB - Hypertension is an independent risk factor for diabetic retinopathy, yet anti
hypertensive medications such as blockade of angiotensin II do not completely
protect against vision-threatening vascular disease. We hypothesized that the
potent vasoactive factor, endothelin (ET), is up-regulated in diabetic
retinopathy and antagonism of the ET type A receptor (ETRA) or ET type B receptor
(ETRB) ameliorates retinal vascular leakage independently of any blood pressure
lowering effects. Spontaneously hypertensive rats (SHR) and their normotensive
and genetic controls, Wistar Kyoto rats, were randomized to become diabetic or
non-diabetic and studied for 8 weeks. Rats were further randomized to receive by
intravitreal injection the ETRA antagonist, BQ123, the ETRB antagonist, BQ788, or
vehicle, 5 days after the induction of streptozotocin diabetes and 4 weeks later.
The treatments had no effect on systolic blood pressure which remained elevated
in SHR. ET-1, ET-2, ETRA and ETRB were expressed in retina and retinal pigment
epithelium (RPE)/choroid and increased by hypertension or diabetes. BQ123 reduced
ET-1 and ET-2 expression in retina and RPE/choroid, while BQ788 had a similar
effect but did not influence the mRNA levels of ET-1 in retina. Retinal vascular
leakage and Muller cell stress as well as vascular endothelial growth factor
(VEGF) expression in retina and RPE/choroid, were increased by hypertension or
diabetes and there was an additive effect of these conditions. Treatment with
BQ123 or BQ788 effectively reduced these events as well as the elevated levels of
inflammatory factors in the retina. Our findings indicate that local ET systems
exist in the retina and RPE/choroid that are up-regulated by hypertension and
diabetes. The ability of locally delivered ET receptor antagonists to supress
these overactive ET systems and reduce retinal vascular leakage and VEGF in the
presence of hypertension indicate the potential of these approaches for the
treatment of diabetic retinopathy.
PMID- 29944851
TI - Potential effect on molecular pathways in different targeted genes in the VEGF
family in retina - From the genomic point of view.
AB - This study's goal is to determine similarities and differences in the molecular
pathways or potential functions of the various targeted regions or genes of the
Vegf family-VegfA, VegfB, VegfC, and Pgf-using the BXD genetic reference panel.
Data from whole genome expression profiles of retinas from the well-characterized
mouse recombinant inbred (RI) strain population derived from C57BL/6J X DBA/2J
(BXD) were analyzed. Multiple analytical tools and statistical strategies were
used to investigate the expression level. The expression Quantitative Trait Loci
(QTLs) of these probes were mapped and compared. Our data showed that VegfA2 has
the highest expression levels among all probes of Vegf genes. The expression
levels of Vegf family genes are not significantly correlated. In the overall
comparison, expression levels of VegfA1 and VegfA2 are positively correlated (R =
0.540). The expression levels of VegfB and VegfC are weakly correlated (R =
0.360). VegfC is also weakly correlated with the expression levels of Pgf (R =
0.324). The interaction of VegfB- and VegfA2-associated 50a2 genes was very weak
(R50 ab = 0.3129). The interaction of top VegfB-associated 50b genes with VegfA2
has a reciprocal negative impact (R50ba = -0.42758). The VegfC-associated top 50c
genes are strongly correlated with VegfB (R50 cb = 0.8159), while they are
negatively correlated with VegfA2 (R50ca = -0.1450). Expression quantitative
trait loci (eQTL) analysis suggested that the regulatory mechanisms for the
expression levels of these genes in the Vegf family are different from each
other. The expression level of VegfA associates with a group of genes that are
not associated with other genes in the Vegf family.
PMID- 29944852
TI - Vitamin D treatment abrogates the inflammatory response in paraquat-induced lung
fibrosis.
AB - A high incidence of intentional or accidental paraquat (PQ) ingestion is related
to irreversible lung fibrosis and no effective therapy is currently available.
Vitamin D has emerged with promising results as an immunomodulatory molecule when
abrogating the inflammatory responses of lung diseases. Therefore, we have
investigated the role of vitamin D treatments on PQ-induced lung fibrosis in male
C57/BL6 mice. Lung fibrosis was induced by a single injection of PQ (10 mg/kg;
i.p.). The control group received PQ vehicle. Seven days later, after the PQ
injection or the vehicle injection, the mice received vitamin D (5 MUg/kg, i.p.,
once a day) or vehicle, for a further 7 days. Twenty-four hours after the last
dose of vitamin D or the vehicle, the analysis were performed. The vitamin D
treatments reduced the number of leukocytes in their BALF and they decreased the
IL-6, IL-17, TGF-beta and MMP-9 levels and the abrogated collagenase deposits in
their lung tissues. Conversely, the vitamin D treatments increased the resolvin D
levels in their BALF. Moreover, their tracheal contractility was also
significantly reduced by the vitamin D treatments. Altogether, the data that was
obtained showed a promising use of vitamin D, in treating the lung fibrosis that
had been induced by the PQ intoxications. This may improve its prognostic use for
a non-invasive and low cost therapy.
PMID- 29944853
TI - Tight Turns of Outer Membrane Proteins: An Analysis of Sequence, Structure, and
Hydrogen Bonding.
AB - As a structural class, tight turns can control molecular recognition, enzymatic
activity, and nucleation of folding. They have been extensively characterized in
soluble proteins but have not been characterized in outer membrane proteins
(OMPs), where they also support critical functions. We clustered the 4 to 6
residue tight turns of 110 OMPs to characterize the phi/psi angles, sequence, and
hydrogen bonding of these structures. We find significant differences between
reports of soluble protein tight turns and OMP tight turns. Since OMP strands are
less twisted than soluble strands, they favor different turn structures types.
Moreover, the membrane localization of OMPs yields different sequence hallmarks
for their tight turns relative to soluble protein turns. We also characterize the
differences in phi/psi angles, sequence, and hydrogen bonding between OMP
extracellular loops and OMP periplasmic turns. As previously noted, the
extracellular loops tend to be much longer than the periplasmic turns. We find
that this difference in length is due to the broader distribution of lengths of
the extracellular loops not a large difference in the median length.
Extracellular loops also tend to have more charged residues as predicted by the
charge-out rule. Finally, in all OMP tight turns, hydrogen bonding between the
side chain and backbone 2 to 4 residues away from that side chain plays an
important role. These bonds preferentially use an Asp, Asn, Ser, or Thr residue
in a beta or pro phi/psi conformation. We anticipate that this study will be
applicable to future design and structure prediction of OMPs.
PMID- 29944855
TI - Natural deep eutectic systems as alternative nontoxic cryoprotective agents.
AB - Natural deep eutectic systems (NADES) are mostly composed of natural primary
metabolites such as sugars, sugar alcohols, organic acids, amino acids and
amines. These simple molecules have been identified in animals living in
environments with extreme temperature amplitudes, being responsible for their
survival at negative temperatures during winter. Herein, we report for the first
time the use of NADES based on trehalose (Treh) and glycerol (Gly) in
cryopreservation, as cryoprotective agents (CPA). The evaluation of the thermal
behaviour of these eutectic systems, showed that NADES have a strong effect on
the water crystallization/freezing and melting process, being able to reduce the
number of ice crystals and hence ice crystal damage in cells, which is a crucial
parameter for their survival, upon freezing. Using this NADES as CPA, it is
possible to achieve similar or even better cellular performance when compared
with the gold standard for cryopreservation dimethyl sulfoxide (DMSO). In this
sense, this work relates the physical properties of the NADES with their
biological performance in cryopreservation. Our comprehensive strategy results in
the demonstration of NADES as a promising nontoxic green alternative to the
conventional CPA's used in cryopreservation methods.
PMID- 29944854
TI - A User's Guide for Phase Separation Assays with Purified Proteins.
AB - The formation of membrane-less organelles and compartments by protein phase
separation is an important way in which cells organize their cytoplasm and
nucleoplasm. In vitro phase separation assays with purified proteins have become
the standard way to investigate proteins that form membrane-less compartments. By
now, various proteins have been purified and tested for their ability to phase
separate and form liquid condensates in vitro. However, phase-separating proteins
are often aggregation-prone and difficult to purify and handle. As a consequence,
the results from phase separation assays often differ between labs and are not
easily reproduced. Thus, there is an urgent need for high-quality proteins,
standardized procedures, and generally agreed-upon practices for protein
purification and conducting phase separation assays. This paper provides
protocols for protein purification and guides the user through the practicalities
of in vitro protein phase separation assays, including best-practice approaches
and pitfalls to avoid. We believe that this compendium of protocols and practices
will provide a useful resource for scientists studying the phase behavior of
proteins.
PMID- 29944856
TI - Mathematical models for chemotaxis and their applications in self-organisation
phenomena.
AB - Chemotaxis is a fundamental guidance mechanism of cells and organisms,
responsible for attracting microbes to food, embryonic cells into developing
tissues, immune cells to infection sites, animals towards potential mates, and
mathematicians into biology. The Patlak-Keller-Segel (PKS) system forms part of
the bedrock of mathematical biology, a go-to-choice for modellers and analysts
alike. For the former it is simple yet recapitulates numerous phenomena; the
latter are attracted to these rich dynamics. Here I review the adoption of PKS
systems when explaining self-organisation processes. I consider their foundation,
returning to the initial efforts of Patlak and Keller and Segel, and briefly
describe their patterning properties. Applications of PKS systems are considered
in their diverse areas, including microbiology, development, immunology, cancer,
ecology and crime. In each case a historical perspective is provided on the
evidence for chemotactic behaviour, followed by a review of modelling efforts; a
compendium of the models is included as an Appendix. Finally, a half-serious/half
tongue-in-cheek model is developed to explain how cliques form in academia.
Assumptions in which scholars alter their research line according to available
problems leads to clustering of academics and the formation of "hot" research
topics.
PMID- 29944857
TI - Disruption of the Zdhhc9 intellectual disability gene leads to behavioural
abnormalities in a mouse model.
AB - Protein S-acylation is a widespread post-translational modification that
regulates the trafficking and function of a diverse array of proteins. This
modification is catalysed by a family of twenty-three zDHHC enzymes that exhibit
both specific and overlapping substrate interactions. Mutations in the gene
encoding zDHHC9 cause mild-to-moderate intellectual disability, seizures, speech
and language impairment, hypoplasia of the corpus callosum and reduced volume of
sub-cortical structures. In this study, we have undertaken behavioural
phenotyping, magnetic resonance imaging (MRI) and isolation of S-acylated
proteins to investigate the effect of disruption of the Zdhhc9 gene in mice in a
C57BL/6 genetic background. Zdhhc9 mutant male mice exhibit a range of
abnormalities compared with their wild-type littermates: altered behaviour in the
open-field test, elevated plus maze and acoustic startle test that is consistent
with a reduced anxiety level; a reduced hang time in the hanging wire test that
suggests underlying hypotonia but which may also be linked to reduced anxiety;
deficits in the Morris water maze test of hippocampal-dependent spatial learning
and memory; and a 36% reduction in corpus callosum volume revealed by MRI.
Surprisingly, membrane association and S-acylation of H-Ras was not disrupted in
either whole brain or hippocampus of Zdhhc9 mutant mice, suggesting that other
substrates of this enzyme are linked to the observed changes. Overall, this study
highlights a key role for zDHHC9 in brain development and behaviour, and supports
the utility of the Zdhhc9 mutant mouse line to investigate molecular and cellular
changes linked to intellectual disability and other deficits in the human
population.
PMID- 29944858
TI - Altered glutamate response and calcium dynamics in iPSC-derived striatal neurons
from XDP patients.
AB - X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disorder endemic to
Panay Island (Philippines). Patients present with generalizing dystonia and
parkinsonism. Genetic changes surrounding the TAF1 (TATA-box binding protein
associated factor 1) gene have been associated with XDP inducing a degeneration
of striatal spiny projection neurons. There is little knowledge about the
pathophysiology of this disorder. Our objective was to generate and analyze an in
vitro model of XDP based on striatal neurons differentiated from induced
pluripotent stem cells (iPSC). We generated iPSC from patient and healthy control
fibroblasts (3 affected, 3 controls), followed by directed differentiation of the
cultures towards striatal neurons. Cells underwent characterization of
immunophenotype as well as neuronal function, glutamate receptor properties and
calcium dynamics by whole-cell patch-clamp recordings and calcium imaging.
Furthermore, we evaluated expression levels of AMPA receptor subunits and voltage
gated calcium channels by quantitative real-time PCR. We observed no differences
in basic electrophysiological properties. Application of the AMPA antagonist NBQX
led to a more pronounced reduction of postsynaptic currents in XDP neurons. There
was a higher expression of AMPA receptor subunits in patient-derived neurons.
Basal calcium levels were lower in neurons derived from XDP patients and cells
with spontaneous calcium transients were more frequent. Our data suggest altered
glutamate response and calcium dynamics in striatal XDP neurons.
PMID- 29944859
TI - Binge-like intake of sucrose reduces the rewarding value of sucrose in adult
rats.
AB - Binge eating disorder is the most common eating disorder, but its underlying
etiology is poorly understood. Both humans and animals exhibit binge-like intake
of highly-palatable food, suggesting that the behavior is driven by the rewarding
properties of food, rather than homeostatic signals. Food reward is regulated, in
part, by endogenous opioid mechanisms which, themselves, may be altered by
excessive eating. We examined this hypothesis by testing whether binge-like
sucrose intake modifies the subsequent development of a conditioned place
preference (CPP) to sucrose and morphine in both female and male adult rats.
Separate groups were given intermittent (12h) or continuous (24 h) access to a
sweet solution (10% sucrose or 0.1% saccharin) and food in their home cage over
28 days. Intermittent sucrose access induced binge-like intake, defined as
increased consumption within the first hour; importantly, daily sucrose intake
was similar for continuous and intermittent access groups. In a later test, all
rats developed a conditioned place preference (CPP) to 15% sucrose with the
exception of female and male rats given 12-h intermittent access to sucrose. In a
separate experiment, all groups displayed a CPP to morphine (4 mg/kg). These
findings demonstrate that binge-like sucrose intake, not just increased
consumption, disrupts reward processing without affecting stimulus-reward
learning. This fits with clinical evidence of hypo-reward responsivity in
patients with binge eating disorder.
PMID- 29944860
TI - Modulation of learning and memory by the genetic disruption of circadian
oscillator populations.
AB - While a rich literature has documented that the efficiency of learning and memory
varies across circadian time, a close survey of that literature reveals extensive
heterogeneity in the time of day (TOD) when peak cognitive performance occurs.
Moreover, most previous experiments in rodents have not focused on the question
of discriminating which memory processes (e.g., working memory, memory
acquisition, or retrieval) are modulated by the TOD. Here, we use assays of
contextual fear conditioning and spontaneous alternation in WT (C57Bl/6 J) mice
to survey circadian modulation of hippocampal-dependent memory at multiple
timescales - including working memory (seconds to a few minutes), intermediate
term memory (a delay of thirty minutes), and acquisition and retrieval of long
term memory (a delay of two days). Further, in order to test the relative
contributions of circadian timing mechanisms to the modulation of memory, a
parallel set of studies were performed in mice lacking clock timing mechanisms.
These transgenic mice lacked the essential circadian gene Bmal1, either globally
(Bmal1 null) or locally (floxed Bmal1 mice, which lack Bmal1 in excitatory
forebrain neurons, e.g. cortical and hippocampal neurons). Here, we show that in
WT mice, retrieval (but not working memory, intermediate-term memory, or
acquisition of long-term memory) is modulated by TOD. However, transgenic mouse
models lacking Bmal1 - both globally, and only in forebrain excitatory neurons -
show deficits regardless of the memory process tested (and lack circadian
modulation of retrieval). These results provide new clarity regarding the impact
of the TOD on hippocampal-dependent memory and support the key role of
hippocampal and cortical circadian oscillations in circadian gating of cognition.
PMID- 29944861
TI - Synaptic modification by L-theanine, a natural constituent in green tea, rescues
the impairment of hippocampal long-term potentiation and memory in AD mice.
AB - Synaptic refinement improves synaptic efficiency, which provides a possibility to
improve memory in Alzheimer's disease (AD). In the current study, we aimed to
investigate the role of L-theanine, a natural constituent in green tea, in
hippocampal synaptic transmission and to assess its potential to improve memory
in transgenic AD mice. Initially, we found that L-theanine bath application
facilitated hippocampal synaptic transmission and reduced paired-pulse
facilitation (PPF). These effects were blocked by antagonists of N-methyl-D
aspartic acid receptors and the dopamine D1/5 receptor, and a selective protein
kinase A (PKA) inhibitor. Moreover, L-theanine enhanced PKA phosphorylation via
dopamine D1/5 receptor activation. L-theanine did not influence hippocampal long
term potentiation (LTP) in the slices obtained from wild-type mice, but rescued
the impairment of hippocampal LTP in AD mice. Importantly, systemic application
of L-theanine also improved memory and hippocampal LTP in AD mice. Our results
demonstrate that L-theanine administration promotes hippocampal dopamine and
noradrenaline release, and stimulates PKA phosphorylation. Moreover, the rescued
hippocampal LTP in AD mice could be impaired by a PKA inhibitor. Our data reveal
that L-theanine ameliorates the impairment of memory and hippocampal LTP in AD
mice, likely through dopamine D1/5 receptor-PKA pathway activation. These data
warrant the consideration of L-theanine as a candidate for the treatment of AD.
PMID- 29944862
TI - Knockout of alpha 5 nicotinic acetylcholine receptors subunit alters ethanol
mediated behavioral effects and reward in mice.
AB - Evidence suggests that there is an association between polymorphisms in the
alpha5 nicotinic acetylcholine receptor (nAChR) subunit and risk of developing
alcohol dependence in humans. The alpha5 nAChR subunit has also recently been
shown to modulate some of the acute response to ethanol in mice. The aim of the
current study was to further characterize the role of alpha5-containing (alpha5*)
nAChRs in acute ethanol responsive behaviors, ethanol consumption and ethanol
preference in mice. We conducted a battery of tests in male alpha5 knockout (KO)
mice for a range of ethanol-induced behaviors including hypothermia, hypnosis,
and anxiolysis. We also investigated the effects of alpha5* nAChR on ethanol
reward using the Conditioned Place Preference (CPP) assay. Further, we tested the
effects of gene deletion on drinking behaviors using the voluntary ethanol
consumption in a two-bottle choice assay and Drinking in the Dark (DID, with or
without stress) paradigm. We found that deletion of the alpha5 nAChR subunit
enhanced ethanol-induced hypothermia, hypnosis, and an anxiolytic-like response
in comparison to wild-type controls. The alpha5 KO mice showed reduced CPP for
ethanol, suggesting that the rewarding properties of ethanol are decreased in
mutant mice. Interestingly, Chrna5 gene deletion had no effect on basal ethanol
drinking behavior, or ethanol metabolism, but did decrease ethanol intake in the
DID paradigm following restraint stress. Taken together, we provide new evidence
that alpha5 nAChRs are involved in some but not all of the behavioral effects of
ethanol. Our results highlight the importance of nAChRs as a possible target for
the treatment of alcohol dependence.
PMID- 29944863
TI - Low-grade dysplasia diagnosis ratio and progression metrics identify variable
Barrett's esophagus risk stratification proficiency in independent pathology
practices.
AB - BACKGROUND AND AIMS: The diagnosis of low-grade dysplasia (LGD) in Barrett's
esophagus (BE) is subject to substantial interobserver variation. Our central aim
in this study is to compare independent pathology practices using objective
measures of BE risk stratification proficiency, including frequency of diagnosis
and rate of progression, with high-grade dysplasia (HGD) or adenocarcinoma (EAC)
after the first diagnosis of LGD. METHODS: We retrospectively evaluated over
29,000 endoscopic biopsy cases to identify 4734 patients under endoscopic biopsy
surveillance for BE in a healthcare system with multiple independent pathology
practices: a subspecialized GI pathology group (SSGI; 162 BE cases per
pathologist annually), 3 high BE volume general surgical pathology practices
(GSPs; >50 BE cases per pathologist annually), and multiple low BE volume GSPs
(10.6 BE cases per pathologist annually). We measured LGD diagnosis frequencies
and rates of diagnostic progression to HGD or EAC in patients diagnosed with LGD.
RESULTS: The proportion of all BE cases diagnosed as LGD (LGD/BE diagnosis ratio)
ranged from 1.1% to 6.8% in the different hospital settings (P < .001). The
cumulative proportion of patients with HGD or EAC within 2 years of the first
diagnosis of LGD was 35.3% in the SSGI and ranged from 1.4% to 14.3% in the GSPs
(P < .001). LGD diagnosed by the GSP with the lowest LGD/BE diagnosis ratio had
an adjusted risk of progression similar to LGD diagnosed by subspecialists
(hazard ratio, .42; 95% CI, .06-3.03). However, when LGD was diagnosed by other
generalists, the adjusted risk of progression was 79% to 91% lower than
subspecialists (P < .001). When LGD was diagnosed in a low-volume GSP practice,
the risk of progression was not significantly increased relative to patients with
nondysplastic BE (hazard ratio, 1.3; 95% CI, .4-3.9). CONCLUSIONS: General
surgical pathologists and subspecialists show highly significant differences with
respect to LGD/BE ratio, risk of progression relative to nondysplastic BE, crude
annual progression rates, and the cumulative 2-year progression rate after LGD.
These metrics can be used to assess proficiency in BE risk stratification in
historical cases. Some general practitioners were able to achieve results similar
to subspecialists. General surgical pathologists with little annual experience
evaluating BE biopsy specimens did not successfully risk stratify patients with
BE.
PMID- 29944864
TI - Circulating soluble corin as a potential biomarker for cardiovascular diseases: A
translational review.
AB - Corin is a type II transmembrane serine protease that is highly expressed in the
heart and plays a physiological role in the activation of natriuretic peptides.
Corin is expressed primarily in myocytes, and it can enter the circulation.
Circulating soluble corin has been found to be associated with various
cardiovascular diseases, such as hypertension, heart failure, myocardial
infarction, preeclampsia, and stroke. All these findings indicate that
circulating soluble corin has the potential to be a sensitive and specific
biomarker for risk prediction and prognostic assessment of cardiovascular
diseases. However, there are certain challenges hindering the incorporation of
circulating soluble corin into clinical practice. To provide new ideas based on
the use of corin for risk prediction, prognostic assessment, and clinical
treatment of cardiovascular diseases and to promote the implementation of corin
as a routine laboratory index, we summarize the latest studies of the association
between corin and cardiovascular diseases in recent years and offer some
prospective proposals for future research on corin in this review.
PMID- 29944865
TI - Neural systems of cognitive demand avoidance.
AB - Cognitive effort is typically aversive, evident in people's tendency to avoid
cognitively demanding tasks. The 'cost of control' hypothesis suggests that
engagement of cognitive control systems of the brain makes a task costly and the
currency of that cost is a reduction in anticipated rewards. However, prior
studies have relied on binary hard versus easy task subtractions to manipulate
cognitive effort and so have not tested this hypothesis in "dose-response"
fashion. In a sample of 50 participants, we parametrically manipulated the level
of effort during fMRI scanning by systematically increasing cognitive control
demands during a demand-selection paradigm over six levels. As expected,
frontoparietal control network (FPN) activity increased, and reward network
activity decreased, as control demands increased across tasks. However, avoidance
behavior was not attributable to the change in FPN activity, lending only partial
support to the cost of control hypothesis. By contrast, we unexpectedly observed
that the de-activation of a task-negative brain network corresponding to the
Default Mode Network (DMN) across levels of the cognitive control manipulation
predicted the change in avoidance. In summary, we find partial support for the
cost of control hypothesis, while highlighting the role of task-negative brain
networks in modulating effort avoidance behavior.
PMID- 29944866
TI - Structural changes in cellular membranes induced by ionic liquids: From model to
bacterial membranes.
AB - Ionic liquids (ILs) have generated considerable attention recently because of
their cytotoxicity and application as antibiotics. However, the mechanism of how
they damage cell membranes is not currently well understood. In this paper, the
antibacterial activities of two imidazolium-based ILs, namely 1-butyl- 3
methylimidazolium tetrafluroborate ([BMIM][BF4]) and 1-ethyl- 3-methylimidazolium
tetrafluroborate ([EMIM][BF4]) have been investigated. The activity of
[BMIM][BF4] on gram negative bacteria E. coli is observed to be stronger compared
with the short chained [EMIM][BF4]. To explain this observation, the effects of
these ILs on the self-assembled structures of model cellular membranes have been
investigated. The in-plane elasticity of a monolayer formed at air-water
interface by 1,2-dipalmitoyl- sn-glycero- 3-phosphocholine (DPPC) lipids was
reduced in the presence of the ILs. The x-ray reflectivity studies on polymer
supported lipid bilayer have shown the bilayer to shrink and correspondingly
exhibit an increase in electron density. The presence of a certain mol% of
negatively charged lipid, 1,2-dipalmitoyl-rac-glycero-3-phospho-L-serine (DPPS),
in DPPC mono- and bi-layers enhances the effect considerably.
PMID- 29944867
TI - LncRNA PRAL is closely related to clinical prognosis of multiple myeloma and the
bortezomib sensitivity.
AB - Chromosome 17p deletions (del(17p)) are present in about 11% of newly diagnosed
multiple myeloma (MM) patients and related to inferior prognosis. Bortezomib
(BTZ), the first proteasome inhibitor anticancer drug, has a good therapeutic
effect for newly diagnosed, relapsed or refractory MM, but is unable to improve
the outcome of MM patients with del(17p). Long noncoding RNA (lncRNA) PRAL is
located on chromosome 17p, and is associated with the progression and prognosis
of different types of cancers. However, little is known about its role in MM.
Here, we found that PRAL was downregulated in primary MM cells and cell lines,
especially in MM cells with del(17p), and was associated with ISS (international
staging system) stage and Durie-Salmon stage in MM patients. Survival curves
showed that MM patients with low PRAL expression had a significantly shorter
disease-free survival (DFS) and overall survival (OS) than the patients with high
PRAL expression. Multivariate Cox regression analysis showed that PRAL expression
was an independent predictor for DFS and OS. Then cell proliferation, viability,
Ki67 expression, and caspase-3 activity detection showed that PRAL promoted MM
cell growth inhibition and apoptosis, and potentiated the anti-MM effect of BTZ
in vitro. We further identified and confirmed that miR-210 was the target of
PRAL, and miR-210 overexpression overturned the potentiation effect of PRAL on
BTZ efficacy. Subsequently, bone morphogenetic protein 2 (BMP2) was confirmed to
be the target of miR-210, and PRAL positively regulated the derepression of BMP2
by sponging miR-210. Overexpression of BMP2 potentiated the anti-MM effect of BTZ
in vitro. In addition, animal experiments further confirmed that PRAL potentiated
BTZ efficacy in vivo. Collectively, our study first revealed a critical role of
PRAL-miR-210-BMP2 axis in MM progression, prognosis and treatment with BTZ, and
PRAL could become a novel diagnostic, prognostic and therapeutic candidate for MM
patients especially for the MM patients harboring del(17p) in the future.
PMID- 29944868
TI - Identification of 2, 3-dihydrodipicolinate as the product of the
dihydrodipicolinate synthase reaction from Escherichia coli.
AB - Dihydrodipicolinate synthase (DHDPS) catalyzes the first step in the pathway for
the biosynthesis of L-lysine in most bacteria and plants. The substrates for the
enzyme are pyruvate and L-aspartate-beta-semialdehyde (ASA). The product of the
reaction was originally proposed to be 2,3-dihydrodipicolinate (DHDP), but has
now generally been assumed to be (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)
dipicolinate (HTPA). ASA is unstable at high pH and it is proposed that ASA
reacts with itself. At high pH ASA also reacts with Tris buffer and both
reactions are largely reversible at low pH. It is proposed that the basic un
protonated form of the amine of Tris or the alpha-amine of ASA reacts with the
aldehyde functional group of ASA to generate an imine product. Proton NMR spectra
of ASA done at different pH values shows new NMR peaks at high pH, but not at low
pH, confirming the presence of reaction products for ASA at high pH. The
enzymatic product of the DHDPS reaction was examined at low pH by proton NMR
starting with either 3 h-pyruvate or 3 d-pyruvate and identical NMR spectra were
obtained with four new NMR peaks observed at 1.5, 2.3, 3.9 and 4.1 ppm in both
cases. The NMR results were most consistent with DHDP as the reaction product.
The UV-spectral studies of the DHDPS reaction shows the formation of an initial
product with a broad spectral peak at 254 nM. The DHDPS reaction product was
further examined by reduction of the enzymatic reaction components with
borohydride followed by GC-MS analysis of the mixture. Three peaks were found at
88, 119 and 169 m/z, consistent with pyruvate, homoserine (reduction product of
ASA), and the reduction product of DHDP (1,2,3,6-tetrahydropyridine-2,6
dicarboxylate). There was no indication for a peak associated with the reduced
form of HTPA.
PMID- 29944869
TI - Molecular and functional characterization of UDP-glucuronosyltransferase 1A in
cynomolgus macaques.
AB - UDP-glucuronosyltransferases (UGTs) are drug-metabolizing enzymes essential for
the metabolism of endogenous substrates and xenobiotics. Molecular
characteristics of UGTs have been extensively investigated in humans, but in
cynomolgus macaques, a non-human primate species widely used in drug metabolism
studies, remain to be investigated. In this study, 12 UGT1A cDNAs (UGT1A1, 1A2,
1A4A, 1A4B, 1A5A, 1A5B, 1A5C, 1A6, 1A7, 1A8, 1A9, and 1A10) were isolated and
characterized in cynomolgus macaques. UGT1A5C cDNA did not contain a complete
coding region due to nonsense mutations, and was excluded from further analysis.
Amino acid sequences of all 11 cynomolgus UGT1As had high sequence identities (92
95%) with human UGT1As and were phylogenetically close to human UGT1As. These
cynomolgus UGT1A genes shared exons 2-5, and contained a variable exon 1 unique
to each gene, similar to human UGT1A genes. Moreover, cynomolgus and human UGT1A
gene clusters were located in corresponding regions in the genome. Among the 10
tissue types analyzed, cynomolgus UGT1A mRNAs were most abundantly expressed in
the liver, jejunum, and/or kidney, the drug-metabolizing organs, similar to human
UGT1As. Among these 11 cynomolgus UGT1A mRNAs, cynomolgus UGT1A2, UGT1A9, and
UGT1A10 mRNAs were most abundantly expressed in the liver, kidney, and jejunum,
respectively. Cynomolgus liver microsomes and UGT1A proteins catalyzed
glucuronidation of the substrates human UGT1As catalyze, including 4
methylumbelliferone, 4-nitrophenol, estradiol, trifluoperazine, serotonin, and
propofol, although trifluoperazine glucuronidation was not catalyzed by any
cynomolgus UGT1A proteins. These results suggest that cynomolgus UGT1As are
functional enzymes with molecular similarities to human UGT1As.
PMID- 29944870
TI - Sulfasalazine alters microglia phenotype by competing endogenous RNA effect of
miR-136-5p and long non-coding RNA HOTAIR in cuprizone-induced demyelination.
AB - Sulfasalazine (SF) promotes remyelination and improves the outcome of multiple
sclerosis (MS) patients. However, the underlining mechanism remains elusive.
Here, we examined whether SF blocks microglia switching to a pro-inflammatory M1
like phenotype through a competing endogenous RNA (ceRNA) effects in cuprizone
induced demyelination. The microglia reprogramming effects of SF in the mice
model of cuprizone-induced demyelination was measured by histological,
immunohistochemical and molecular biological methods. We also measured the
effects of the condition media from SF-treated microglia on the differentiation
of OLN-93 cells. Insights of the mechanism of ceRNAs of miR-136-5p and long non
coding RNA (lncRNA) HOTAIR were gained from bioinformatic analysis, luciferase
assays and RNA binding protein immunoprecipitation. Microglia switched to a pro
inflammatory M1-like phenotype in cuprizone induced-demyelination. Conversely, SF
inhibited the M1-like polarization with the increased remyelination which was
attenuated by microglia depletion. SF inhibited production of M1-like factors TNF
alpha and INF-gamma in microglia, and thereby promoted the differentiation of OLN
93 oligodendrocytes. SF down-regulated lncRNA HOTAIR but up-regulated miR-136-5p,
and thus inactivated AKT2-NF-kappaB in cuprizone-treated microglia. Importantly,
lncRNA HOTAIR overexpression reversed the increased miR-136-5p expression by SF
and thereby attenuated the inhibition of AKT2-mediated NF-kappaB activation.
Mimic of miR-136-5p inhibited cuprizone-induced activation of AKT2-NF-kappaB in
the microglia. In summary, SF blocks microglia switching to a pro-inflammatory M1
like phenotype by ceRNA effect of miR-136-5p and lncRNA HOTAIR in cuprizone
induced demyelination. Our findings show the therapeutic potential of SF for
human MS probably by targeting epigenetic regulation in microglia.
PMID- 29944871
TI - Identification of the extracellular matrix protein Fibulin-2 as a regulator of
spinal nerve organization.
AB - During amniote peripheral nervous system development, segmentation ensures the
correct patterning of the spinal nerves relative to the vertebral column. Along
the antero-posterior (rostro-caudal) axis, each somite-derived posterior half
sclerotome expresses repellent molecules to restrict axon growth and neural crest
migration to the permissive anterior half-segment. To identify novel regulators
of spinal nerve patterning, we investigated the differential gene expression of
anterior and posterior half-sclerotomes in the chick embryo by RNA-sequencing.
Several genes encoding extracellular matrix proteins were found to be enriched in
either anterior (e.g. Tenascin-C, Laminin alpha 4) or posterior (e.g. Fibulin-2,
Fibromodulin, Collagen VI alpha 2) half-sclerotomes. Among them, the
extracellular matrix protein Fibulin-2 was found specifically restricted to the
posterior half-sclerotome. By using in ovo ectopic expression in chick somites,
we found that Fibulin-2 modulates spinal axon growth trajectories in vivo. While
no intrinsic axon repellent activity of Fibulin-2 was found, we showed that it
enhances the growth cone repulsive activity of Semaphorin 3A in vitro. Some
molecules regulating axon growth during development are found to be upregulated
in the adult central nervous system (CNS) following traumatic injury. Here, we
found increased Fibulin-2 protein levels in reactive astrocytes at the lesion
site of a mouse model of CNS injury. Together, these results suggest that the
developing vertebral column and the adult CNS share molecular features that
control axon growth and plasticity, which may open up the possibility for the
identification of novel therapeutic targets for brain and spinal cord injury.
PMID- 29944872
TI - Optimization of the ninhydrin reaction and development of a multiwell plate-based
high-throughput proline detection assay.
AB - We developed a high-throughput technique for highly sensitive measurement of
trace amounts of proline, an indicator of drought stress in plants, using an
optimized proline-ninhydrin reaction. In order to do this, proline detection time
was minimized by omitting phosphoric acid from the ninhydrin reagent. Chromophore
extraction using toluene was also omitted, thus lowering the risks to environment
and human health, and allowing the use of readily available polystyrene plates.
Proline detection sensitivity was assessed based on the concentration of
sulfosalicylic acid in the solution, which indicated that 1% sulfosalicylic acid
yielded the best sensitivity and linearity. These findings were applied to a
multiwell plate-based multiplex analysis using a dry oven for the simultaneous
analysis of a large number of drought-stressed plant samples with trace amounts
of proline. The results showed that proline could be effectively detected in
plants grown in soil with water content under 5%, demonstrating its potential for
diagnosing drought early. The proposed multiwell plate-based multiplex assay is
expected to be useful in manifold agricultural applications.
PMID- 29944873
TI - GC-MS quantification of urinary symmetric dimethylarginine (SDMA), a whole-body
symmetric l-arginine methylation index.
AB - Circulating and excretory NG,N'G-dimethyl-l-arginine (symmetric dimethylarginine,
SDMA) and NG,NG-dimethyl-l-arginine (asymmetric dimethylarginine, ADMA) are
cardiovascular risk factors. Despite close chemical structures, the gas
chromatography-mass spectrometry (GC-MS) measurement of SDMA is remarkably more
difficult than that of ADMA for as yet unknown reasons. Here, we describe an
improved GC-MS method for the quantitative determination of SDMA in human urine
using commercially available NG,N'G-di-[2H3]methyl-l-arginine (d6-SDMA) as
internal standard. The method is based on a single derivatization step with
pentafluoropropionic anhydride (PFPA) in ethyl acetate (30 min, 65 degrees C) to
N,N,N,O-tetrakis-pentafluoropropionyl derivatives, electron-capture negative-ion
chemical ionization and selected-ion monitoring of the mass-to-charge (m/z) ions
of m/z 456 for SDMA and m/z 462 for d6-SDMA.
PMID- 29944874
TI - Does C-Arm Guidance Improve Reduction of Zygomatic Arch Fractures?-A Randomized
Controlled Trial.
AB - PURPOSE: Traditionally, in the assessment of the reduction of zygomatic arch
fractures, the surgeon uses subjective measures such as palpation of a bony step
deformity, the anecdotal "pop" sounds, and visual confirmation of symmetry. In
the present study, we sought to objectively assess the accuracy of reduction and
improvement in form and function after C-arm-guided reduction of isolated
zygomatic arch fractures (IZAFs) and to compare these results with those obtained
conventionally. PATIENTS AND METHODS: A prospective, randomization of patients
scheduled for surgical closed reduction of IZAF was performed. The test group
underwent C-arm-guided reduction of the fracture until the arch contour was re
established and visualized on fluoroscopic images. In the control group,
palpation, auditory cues, and visualization of symmetry determined the adequacy
of the reduction. The patients and evaluator were both unaware of the treatment
technique used. The primary outcome measures were the maximum interincisal
distance (IID), standardized measurements on computed tomography (CT), and
measures of symmetry on facial photographs. Variables such as intragroup
differences and patient-evaluator agreement were also studied. The data were
analyzed using SPSS software, version 21. RESULTS: The study sample consisted of
20 patients (10 each in the test and control groups). Significant improvement in
facial symmetry was observed in all 20 patients (P < .001) from preoperatively to
30 days postoperatively. The CT measurements confirmed acceptable symmetry, with
insignificant differences between the 2 groups (C-arm group, P < .001; vs control
group, P = .004 for intragroup improvement in symmetry). The IID had improved
significantly (P < .001) at the end of follow-up in both groups. CONCLUSIONS:
Although significantly superior outcomes were not inferred in the symmetry
related and CT measurements, C-arm-guided reduction provided an opportunity to
instantaneously confirm the accuracy of bony reduction. Thus, the need for
postoperative imaging and secondary surgery can be overcome, enabling even
inexperienced surgeons to attain precise and reproducible results.
PMID- 29944875
TI - Family planning and contraception use in transgender men.
AB - OBJECTIVES: Female-to-male (FTM) transgender men (affirmed males) can experience
planned and unplanned pregnancy during and after testosterone therapy. We
conducted an exploratory study to understand current contraceptive practices and
fertility desires among transgender men during and after transitioning. STUDY
DESIGN: Self-identified transgender and transmasculine individuals assigned
female at birth, ages 18-45, completed an anonymous online survey derived from
standardized family planning surveys. We recruited participants from LGBT health
centers, online listservs, and online groups for transgender men and used a mixed
methods analysis to evaluate quantitative and qualitative data. RESULTS: Of the
one hundred and ninety-seven participants included in the study, the median age
was 30 years old, most respondents were white, and 86% were taking masculinizing
hormones (testosterone). Of the 60 pregnancies reported, 10 (17%) pregnancies
occurred after stopping testosterone, 1 (1.6%) while taking testosterone
irregularly, and 5 of 7 abortions occurred in participants who had been using
testosterone in the past. Over half of the respondents desired at least one
child, and a quarter reported fears of not getting pregnant. The majority of
participants reporting using contraception (n=110, 60.1%), with condoms and pills
used most commonly (n=90, 49.2% and n=62, 33.9% respectively). Methods of
contraception used did not differ between testosterone users and non-users,
except for hormonal IUDs (20% testosterone versus 7% non-testosterone). Thirty
participants (16.4%) believed that testosterone was a form of contraception, and
10 (5.5%) participants reported that their healthcare providers advised
testosterone as contraception. CONCLUSION: Transgender men use contraception and
can experience pregnancy and abortion, even after transitioning socially and
hormonally. Transgender men need counseling and care regarding reproductive
health, including contraceptive and conception counseling. IMPLICATIONS:
Providers should be aware that transgender men may desire pregnancy and use
contraception; this study highlights the need for further research regarding
fertility, fertility desires, and optimal contraception among transgender men.
PMID- 29944876
TI - Hesperidin protects against stress induced gastric ulcer through regulation of
peroxisome proliferator activator receptor gamma in diabetic rats.
AB - Stress induced gastric ulcer is a serious health problem in diabetic patients.
Some studies reported that hesperidin (HDN), a citrus bioflavonoid, can bind to
and stimulate peroxisome proliferator-activator receptor-gamma (PPAR-gamma) which
may mediate its antidiabetic, anti-inflammatory and anti-oxidant effects. This
work aims to study the possible protective effect of HDN against stress induced
gastric ulcer in diabetic rats as well as the possible involvement of PPARgamma
in this effect. Type 2 diabetes was induced using streptozotocin and
nicotinamide. Diabetic rats received either HDN (100 mg/kg/day, orally) &
omeprazole (20 mg/kg/day, orally) or HDN (100 mg/kg/day, orally) + GW9662,
PPARgamma antagonist, (1 mg/kg/day, i.p.) for 8 weeks then acute gastric injury
was induced by cold restraint stress technique. Glycemic controls and
gastroprotective effects were evaluated by measuring serum levels of glucose and
insulin, gastric free and total acidity and gastric ulcer indices.
Histopathological examination of gastric mucosa was also performed. To determine
the underlying mechanism of action, gastric mucosal expression of nuclear factor
(erythroid-derived 2)-like 2 (Nrf2), hemeoxygenase-1 (HO-1), cluster of
differentiation 45 (CD45), cyclooxygenase-2 (COX-2), nuclear factor kappa B
(NFkappaB) and inducible nitric oxide synthase (iNOS), gastric contents of
reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha
(TNF-alpha) and nitric oxide (NO); as well as superoxide dismutase (SOD) and
catalase activities were measured. HDN significantly improved glycemic level; it
also reduced gastric acidity and gastric ulcer index and histopathological
changes comparable to that produced by omeprazole. Moreover, HDN reduced lipid
peroxidation and inflammatory markers levels and enhanced antioxidant capacity.
The use of GW9662 significantly abrogated the gastric protective effect of HDN as
well as reduced the antioxidant and anti-inflammatory effects. Our work showed,
for the first time that, HDN has promising protective effect against stress
induced gastric ulcer in diabetic rats through activation of PPARgamma.
PMID- 29944878
TI - Isolated Severe Right Ventricular Hypertrophic Cardiomyopathy.
AB - A 26-year-old woman diagnosed with congenital heart disease was admitted to our
hospital with exertional dyspnea, cyanotic complexion, and bilateral lower limb
edema. All tests revealed isolated severe right ventricular (RV) hypertrophy. She
was in poor condition, with a diminishing chance for routine surgery, so she was
scheduled for orthotopic homologous heart transplantation. After the surgery,
isolated severe RV hypertrophic cardiomyopathy (RV HCM) was confirmed
histologically and pathologically. After the surgery, the patient's cardiac
function was normal. Exertional dyspnea, cyanotic complexion and bilateral lower
limb edema all improved postoperatively.
PMID- 29944879
TI - Invited Commentary.
PMID- 29944877
TI - Correlation of structural features of novel 1,2,3-triazoles with their neurotoxic
and tumoricidal properties.
AB - Triazoles are interesting templates for novel chemotherapeutic drugs. We
synthesized here 17 1,3,4-substituted-1,2,3-triazoles that differed in their 1'
substituent (variable alkyl chain lengths C3-C12), the 3'-substituent (no
substituent, -methyl or -propyl) or the salt form obtained. Several of the
compounds were cytotoxic (MUM range) for tumor cells (HL-60, Jurkat, MCF-7, HCT
116), and when the effect was compared to non-transformed cells (Vero),
selectivity ratios of up to 23-fold were obtained. To estimate the liability of
these potential drug candidates for triggering neurotoxicity, we used the LUHMES
cell-based NeuriTox assay. This test quantifies damage to the neurites of human
neurons. The four most potent tumoricidal compounds were found to be neurotoxic
in a concentration range similar to the one showing tumor cell toxicity. As the
neurites of the LUHMES neurons were affected at >4-fold lower concentrations than
the overall cell viability, the novel triazoles were classified as specific
neurotoxicants. The structure-activity relationship (SAR) for neurotoxicity was
sharply defined and correlated with the one for anti-neoplastic activity. Based
on this SAR, two non-neurotoxic compounds were predicted, and testing in the
NeuriTox assay confirmed this prediction. In summary, the panel of novel
triazoles generated and characterized here, allowed to define structural features
associated with cytotoxicity and neurotoxicity. Moreover, the study shows that
potential neurotoxic side effects may be predicted early in drug development if
highly sensitive test methods for neurite integrity are applied.
PMID- 29944880
TI - Preoperative Sarcopenia Portends Worse Outcomes After Descending Thoracic Aortic
Aneurysm Repair.
AB - BACKGROUND: Sarcopenia may be an indicator of frailty. We used the total psoas
area index (TPAI) to identify sarcopenia and evaluated the effect of preoperative
TPAI on outcomes after descending thoracic aortic aneurysm (DTAA) repair.
METHODS: Patients with DTAA between 2007 and 2015 who were undergoing thoracic
endovascular aortic repair (TEVAR) and open surgical repair (OSR) with available
preoperative imaging were analyzed. Sarcopenia was defined as TPAI <6.5cm2/m2. An
adverse event was defined as the composite endpoint of three or more multisystem
complications, discharge to other than home, or death within 30 days. RESULTS: A
total of 282 of 386 DTAA repairs had imaging available for TPAI measurements; 71
of 282 (25%) patients underwent TEVAR, and 211 of 282 (75%) underwent OSR.
Preoperative sarcopenia was similar in the two groups (OSR, 57% vs TEVAR, 48%, p
= 0.188). Risk factors for sarcopenia were age >70 years, female sex, and large
body surface area, whereas heritable thoracic aortic disease was a protective
factor. OSR-treated patients with sarcopenia were older compared with patients
without sarcopenia (p < 0.001), whereas TEVAR-treated patients had a similar age
category distribution (p = 0.187). Patients with sarcopenia had significantly
increased adverse events compared with patients who did not have sarcopenia in
both groups (sarcopenia-TEVAR, 41% vs nonsarcopenia-TEVAR, 16%, p = 0.020;
sarcopenia-OSR, 49% vs nonsarcopenia-OSR, 32%, p = 0.012). Determinants of long
term mortality were increasing age (parameter estimate [PE], 0.06, p < 0.001),
TPAI as a decreasing linear function (PE, 0.36, p = 0.003), OSR (PE, 2.92, p =
0.003), and interaction between OSR and TPAI (PE, -0.34, p = 0.010). The
interaction term showed that OSR increases long-term mortality risk in more
sarcopenic patients. CONCLUSIONS: Preoperative sarcopenia significantly
correlated with postoperative adverse events and long-term mortality after DTAA
repair. If anatomically feasible, TEVAR should be considered in sarcopenic
patients.
PMID- 29944881
TI - Excess Cost and Predictive Factors of Esophagectomy Complications in the SEER
Medicare Database.
AB - BACKGROUND: Postoperative complications result in significantly increased health
care expenditures. The objective of this study was to examine 90-day excess costs
associated with inpatient complications after esophagectomy and their predictive
factors, by using the Surveillance, Epidemiology, and End Results (SEER)-Medicare
database. METHODS: The study examined patients older than 65 years of age with a
diagnosis from 2002 to 2009 and who were undergoing esophagectomy for cancer in
the SEER-Medicare database. Quantile regression models were fit at 5% intervals
for excess 90-day cost associated with perioperative complications while
controlling for baseline characteristics. Excess cost was defined as the
difference in total cost for patients with versus without the complication.
Analyses were stratified by patients' characteristics to identify factors
predictive of excess cost. RESULTS: A total of 1,462 patients were identified in
the cohort; 51% had at least one complication. Significant excess cost was
associated with pulmonary and mechanical wound complications across all quantiles
(p < 0.05). Infectious (0.35 to 0.75 quantiles), intraoperative (0.05 to 0.85
quantiles), and systemic (0.30 to 0.85 quantiles) complications were associated
with higher costs. Further, excess costs were significantly elevated in the
higher quantiles. At the 0.50 quantile (median) of total cost distribution,
excess cost in patients with any complication were significantly higher in
patients with the following characteristics: transthoracic esophagectomy,
emergency esophagectomy, Charlson Comorbidity Index >0, living in a
nonmetropolitan area or poorer community, or treated in larger hospitals; no such
difference was identified in patients without complications. CONCLUSIONS:
Complications after esophagectomy result in significant excess 90-day cost.
Efforts at cost reduction and quality improvement will need to focus on reducing
complications, in particular pulmonary and infectious, as well as risk factors
for higher complication costs.
PMID- 29944883
TI - Isolation of human monoclonal antibodies that bind to two different antigens and
are encoded by germline VH and VL genes.
AB - This paper reports isolation of two monoclonal antibodies (mAbs) that bind to
both a membrane protein and a cytoplasmic protein. Most Abs established as
markers for autoimmune disease bind to cytoplasmic or nuclear substances.
However, it remains unknown how these Abs are produced. On the other hand, there
were examples where clones originally isolated as Abs that bind to membrane
proteins also showed binding activity to cytoplasmic or nuclear substances. Based
on these results, the following hypothesis has been proposed. The Abs that had
been originally produced against a membrane protein showed cross-reactivity
against cytoplasmic or nuclear substances. In the present study we reported
isolation of Abs that bound to both a membrane protein, CADM1, and a cytoplasmic
protein, alpha-actinin-4. The method adopted in the present study could be
generally applicable to isolation of Abs showing such dual specificity. Firstly,
we constructed a huge human Ab library using various organs including naive B
cell-rich organs such as bone marrow and umbilical cords. Then, we developed a
comprehensive screening method for isolation of Abs that bound to cell surface
antigens. Through extensive screenings with many kinds of cell we newly obtained
a library composed of around 4000 independent clones that bind to membrane
proteins. We screened this library with alpha-actinin-4 and succeeded in
isolating two Abs. They bound to alpha-actinin-4 and a membrane protein CADM1.
Furthermore, they are encoded by naive heavy and light chain variable genes (VH &
VL). These results suggested that cross-reactive Abs to both a membrane protein
and a cytoplasmic protein could be present in germline repertoire of Ab in
humans. This methodology adopted in the present study could be applied to
isolation of cross-reactive Abs possibly involved in autoimmune diseases.
PMID- 29944882
TI - The HMW2 adhesin of non-typeable Haemophilus influenzae is a human-adapted lectin
that mediates high-affinity binding to 2-6 linked N-acetylneuraminic acid
glycans.
AB - Non-typeable Haemophilus influenzae (NTHi) is a human-adapted bacterial pathogen,
responsible for infections of the human respiratory tract. This pathogen
expresses a range of adhesins that mediate binding to host cells. Most NTHi
strains can express the related adhesins HMW1 and HMW2. Expression of HMW
proteins is phase-variable: changes in the length of simple-sequence repeats
located in the encoding genes promoter regions results in changes in expression
levels of these adhesins. HMW expression is also controlled by epigenetic
regulation. HMW1 has been previously demonstrated to bind alpha 2-3 sialyl
lactosamine, but affinity of this interaction has not been investigated. The host
receptor(s) for HMW2 is currently unknown. We hypothesized that host glycans may
act as receptors for HMW2-mediated adherence. We examined the glycan-binding
activity of HMW2 using glycan arrays and Surface Plasmon Resonance (SPR). These
studies demonstrate that HMW2 binds 2-6 linked N-acetylneuraminic acid with high
affinity. HMW2 did not bind glycan structures containing the non-human form of
sialic acid, N-glycolylneuraminic acid. Thus, the specificity of HMW1 and HMW2
have complementary lectin activities that may allow NTHi distinct niches in the
human host.
PMID- 29944884
TI - The anti-tumor effect of regorafenib in lung squamous cell carcinoma in vitro.
AB - Lung squamous cell carcinoma (LSCC) is a common type of non-small-cell lung
cancer (NSCLC) and lacks effective treatment. Regorafenib, an oral multikinase
inhibitor, has demonstrated promising anti-tumor activity in various solid
tumors. To study whether regorafenib inhibits LSCC cells, we investigate the
compound in several LSCC cell lines and explore the possible mechanism. In this
study, we confirmed that regorafenib had anti-proliferation effect on LSCC cell
lines by inducing G0/G1 arrest. In addition, glycogen synthase kinase 3beta
(GSK3beta) remained at the same level and Ser9 phosphorylation of GSK3beta
decreased with increasing incubation time and increasing regorafenib
concentration in LSCC cells. GSK3beta inhibition enhanced the anti-tumor activity
of regorafenib. Thus, GSK3beta activation restricted the anti-cancer effect of
regorafenib on LSCC. In conclusion, regorafenib might be a promising drug for
LSCC therapy. GSK3beta might be a potential target to increase the anti-tumor
effect of regorafenib in LSCC cells.
PMID- 29944885
TI - Circ-UBR5: An exonic circular RNA and novel small nuclear RNA involved in RNA
splicing.
AB - Circular RNAs (circRNAs) are class of non-coding RNAs formed by back-splicing
events as loops, and could be found in all types of organisms. They play
important and diverse roles in cell development, growth, and tumorigenesis, but
functions of the majority of circRNAs remain enigmatic. Particularly functional
phenotypes of great majority of circRNAs are not obvious. Here we randomly
selected a circRNA circ-UBR5, which has no obvious functional phenotype in non
small cell lung cancer (NSCLC) cells from our previous research findings, to
explore its potential function in cells. Differential expression of circ-UBR5 was
detected in paired samples of tumorous tissues and adjacent nontumorous tissues
from 59 patients with NSCLC by real-time quantitative reverse transcription
polymerase chain reactions (qRT-PCRs). Results showed circ-UBR5 expression was
significantly downregulated in NSCLC tissues (p < 0.001) and was correlated with
tumor differentiation (p = 0.00126), suggesting circ-UBR5 might serve as an index
of NSCLC differentiation. Our findings indicated circ-UBR5 could bind splicing
regulatory factor QKI, KH domain containing RNA binding (QKI) and NOVA
alternative splicing regulator 1 (NOVA1) and U1 small nuclear RNA (snRNA) in the
nucleus, revealing circ-UBR5 might be a novel snRNA involved in RNA splicing
regulatory process. Moreover, we first presented a highly efficient strategy for
finding specific circRNA binding proteins using Human Protein Microarray
(HuprotTM Protoarray).
PMID- 29944886
TI - Down-regulation of LHPP in cervical cancer influences cell proliferation,
metastasis and apoptosis by modulating AKT.
AB - Cervical cancer is a leading severe malignancy throughout the world. Though
various pathologies associated with cervical cancer progression have been
demonstrated, further study is still necessary to reveal the tumorigenesis of
cervical cancer. The protein histidine phosphatase LHPP is reported as a tumor
suppressor. Histidine phosphorylation, also known as hidden phosphoproteome, is a
poorly characterized post-translational modification of proteins. LHPP is
evolutionarily conserved from worm to human. In the present study, we discovered
that LHPP expression levels were lower in human cervical cancer tumors than that
in adjacent normal tissue samples. LHPP expression levels were also reduced in
several cervical cancer cell lines. Further, LHPP over-expression reduced the
cell proliferation, migration and invasion, associated with the change of p53 and
metastasis signaling pathways. Moreover, over-expressing LHPP markedly induced
apoptosis in human cervical cancer cells via promoting the cleaved Caspse-3 and
PARP. Importantly, we found that LHPP over-expression blocked AKT activation.
Elevating AKT activity could abolish the role of LHPP over-expression in reducing
cell proliferation and metastasis, as well as in inducing apoptotic response.
Moreover, suppressing p53 expression with its inhibitor of PFTalpha abrogated the
activity of LHPP to impede cell proliferation and metastasis, and to trigger
apoptosis. AKT phosphorylation also restrained p53 expression levels in cervical
cancer cells. In vivo, the anti-cervical cancer effects of LJPP were verified,
which were also via the repression of cell proliferation and metastasis, and the
induction of apoptosis. Therefore, LHPP could be considered as an effective
candidate to develop effective therapeutic strategy against cervical cancer
development.
PMID- 29944887
TI - Long noncoding RNA LINC00858 promotes osteosarcoma through regulating miR-139
CDK14 axis.
AB - Long noncoding RNAs (lncRNAs) have been identified to modulate the tumorigenesis
of human cancers. The in-depth of lncRNAs on human osteosarcoma oncogenesis is
still ambiguous. In present study, functional and mechanism experiments were
conducted to investigate the role of long intergenic non-protein coding RNA 00858
(LINC00858) on human osteosarcoma tumorigenesis. Results demonstrated that
LINC00858 expression was significantly upregulated in both osteosarcoma tissues
and cell lines. Mechanism assays presented that LINC00858 silencing significantly
repressed osteosarcoma cells' proliferation and invasion in vitro, and inhibited
the tumor growth in vivo. In further experiments, LINC00858 was identified to
sponge miR-139 to form RNA-induced silencing complex (RISC) using luciferase
reporter assay and RNA immunoprecipitation (RIP). Besides, CDK14 was validated to
be the target protein the miR-139. Rescue experiments confirmed the role of
LINC00858/miR-139/CDK14 pathway on osteosarcoma cells' phenotype. In summary,
these data prove that LINC00858/miR-139/CDK14 axis promotes the tumorigenesis of
osteosarcoma, providing a new mechanism or target for osteosarcoma.
PMID- 29944888
TI - The Initial Response of a Eukaryotic Replisome to DNA Damage.
AB - The replisome must overcome DNA damage to ensure complete chromosome replication.
Here, we describe the earliest events in this process by reconstituting
collisions between a eukaryotic replisome, assembled with purified proteins, and
DNA damage. Lagging-strand lesions are bypassed without delay, leaving daughter
strand gaps roughly the size of an Okazaki fragment. In contrast, leading-strand
polymerase stalling significantly impacts replication fork progression. We reveal
that the core replisome itself can bypass leading-strand damage by re-priming
synthesis beyond it. Surprisingly, this restart activity is rare, mainly due to
inefficient leading-strand re-priming, rather than single-stranded DNA exposure
or primer extension. We find several unanticipated mechanistic distinctions
between leading- and lagging-strand priming that we propose control the
replisome's initial response to DNA damage. Notably, leading-strand restart was
specifically stimulated by RPA depletion, which can occur under conditions of
replication stress. Our results have implications for pathway choice at stalled
forks and priming at DNA replication origins.
PMID- 29944889
TI - Infectivity and growth kinetics of Herpes Simplex Virus type-2 in MOLT4 CCR5+ and
CEM CCR5+ T cell lines.
AB - Herpes simplex virus type-2 (HSV-2) is an important sexually transmitted pathogen
that infects the genital mucosal epithelial cells causing ulcerative lesions at
the site of entry, facilitating HIV infection. The infection of epithelial cells
and skin resident dendritic cells with HSV-2 causes a release of chemokine and
retinoic acid which attracts CD4+ T-cells to the genital mucosa. In this study,
we investigated whether HSV-2 (ATCC VR734) could infect and replicate in two T
cell lines (CEM CCR5+ and MOLT4 CCR5+). The growth of HSV-2 was assessed by
plaque assay while the intracellular HSV-2 was identified using infectious center
and indirect immunofluorescence assays. The replication of HSV-2 in T-cell lines
was compared to a cell line (Vero) which is routinely used for growing HSV-2.
Analysis indicated that a low level of infection was detected in the two T-cells
lines and was dependent on the infectious dose as well as the time of adsorption.
Indirect immunofluorescence showed presence of HSV-2 antigens in the CEM CCR5+
and Vero cell lines but not in MOLT4 CCR5+. The data suggests that T-cells can
support growth of HSV-2 which might contribute to changes in gene expression of T
cells. This is an important aspect that needs to be further investigated in
relation of HIV-1/HSV-2 viral synergy.
PMID- 29944890
TI - Genome-wide identification of genes regulated by RcsA, RcsB, and RcsAB
phosphorelay regulators in Klebsiella pneumoniae NTUH-K2044.
AB - Rcs phosphorelay system is a two-component signal transduction system, which can
regulate the transcription of capsule polysaccharide and biofilm related genes in
Enterobacteriaceae. In this study, microarray technology was used to investigate
the overall genes regulated by RcsA, RcsB, and RcsAB and the regulation mechanism
in Klebsiella pneumoniae, then COG analysis was performed to explore the
functions of the differentially expressed genes. According to the microarray data
result, a total of 45, 223 and 217 genes regulated by RcsA, RcsB, and RcsAB were
screened. The result of COG analysis suggested that inorganic ion transport and
metabolism related genes have a majority in RcsA regulating genes. Most of RcsB
regulated genes were showed involved in energy production and conversion process.
Besides Carbohydrate transport and metabolism genes were identified as the major
components of the RcsAB regulated genes. 15 differentially expressed genes were
confirmed by quantitative real-time PCR (RT-qPCR). The RT-qPCR results indicated
that 13 genes consistent with microarray data. The results of this study provided
important evidence for further research to investigate the influence of RcsA,
RcsB, RcsAB regulators and further efforts to address the diseased caused by
K.pneumoniae, such as pneumonia, bacteremia, and urinary tract infection.
PMID- 29944891
TI - Automated detection of electroencephalography artifacts in human, rodent and
canine subjects using machine learning.
AB - BACKGROUND: Electroencephalography (EEG) invariably contains extra-cranial
artifacts that are commonly dealt with based on qualitative and subjective
criteria. Failure to account for EEG artifacts compromises data interpretation.
NEW METHOD: We have developed a quantitative and automated support vector machine
(SVM)-based algorithm to accurately classify artifactual EEG epochs in awake
rodent, canine and humans subjects. An embodiment of this method also enables the
determination of 'eyes open/closed' states in human subjects. RESULTS: The levels
of SVM accuracy for artifact classification in humans, Sprague Dawley rats and
beagle dogs were 94.17%, 83.68%, and 85.37%, respectively, whereas 'eyes
open/closed' states in humans were labeled with 88.60% accuracy. Each of these
results was significantly higher than chance. COMPARISON WITH EXISTING METHODS:
Other existing methods, like those dependent on Independent Component Analysis,
have not been tested in non-human subjects, and require full EEG montages,
instead of only single channels, as this method does. CONCLUSIONS: We conclude
that our EEG artifact detection algorithm provides a valid and practical solution
to a common problem in the quantitative analysis and assessment of EEG in pre
clinical research settings across evolutionary spectra.
PMID- 29944892
TI - Twists, turns and trade: A new look at the Indian Screw tree (Helicteres isora).
AB - ETHNOPHARMACOLOGICAL RELEVANCE: This is the first study of global trade in fruits
of the widely used traditional medicine, Helicteres isora L. It is used in
Ayurvedic, Siddha, Unani medical systems and/or local folk traditional medicines
in Bangladesh, India and Pakistan. The roots are used in Traditional Chinese
Medicines in China and the fruits in jamu products in Indonesia, Malaysia and
Thailand. In addition, H. isora fruits are also used in "traditional" medical
systems far beyond the natural distribution of this species, for example in Zulu
herbal medicine (South Africa) and Kurdish herbal medicines (Iraq). AIMS OF THE
STUDY: This study had three aims: (i) to assess the global trade in H. isora
fruits; (ii) to study the H. isora trade from West Timor to Java in terms of
actors and prices along the value chain and (iii) to get a better understanding
of the potential of this species to improve household income in eastern
Indonesia. MATERIALS AND METHODS: This study uses historical records, a
contemporary analysis of global trade data (2014-2016) and field assessments of
value chains and the biological factors influencing H. isora fruit production.
RESULTS: Globally, the major exporter of H. isora fruits is India, which exports
H. isora fruits to 19 countries, far beyond the natural geographical distribution
of this species. Over a 36-month period (January 2014-December 2016), India
exported 392 t of H. isora fruits, with a Free-On-Board (FOB) value of Indian
rupiah (INR) 18,337,000 (US$ 274,055). This represents an average annual export
quantity of about 130,526 kg/year. Over this three year period, most of these
exports (85.5%) were to Indonesia (346.58 t), followed by Thailand (6.85%).
Indian H. isora exports are also used in many other medical systems, including
Kurdish and Zulu "traditional" medicines in Iraq and South Africa. Formation of
an Indian diaspora in Bahrain, Mauritius, South Africa, Tanzania and Trinidad and
Tobago over the past 130 years is one of the drivers of H. isora fruit trade
outside the natural geographic distribution of the species. In Indonesia, demand
for H. isora fruits is supplemented by an intra-island trade in Java and an inter
island trade from East Nusa Tenggara. West Timor, for example, exports around 31
37 t of air-dried H. isora fruits per year to Java. At the farm gate, local
harvesters in West Timor get 4000 IDR (c. 0.3 US$) per kg, with businesses in
Java paying 25,000 IDR (c.US$2) per kg for H. isora fruits. This is similar to
the price paid for H. isora fruits imported from India to Java. CONCLUSIONS:
India is the major exporter of whole dried H. isora fruits, including to
countries where this species has never been in traditional use. In Indonesia, H.
isora fruit extracts are used in the cosmetic industry as well as in jamu herbal
medicines, including "Tolak Angin", the country's most popular commercial "jamu"
preparation. Indonesia also is the major importer of H. isora fruits from India.
In eastern Indonesia, improved income to local villagers from the H. isora fruit
trade could come from improved H. isora fruit quality due to better drying
techniques. This would also reduce health risks along the supply chain from to
mycotoxins that have been recorded on poorly dried H. isora fruits. There also is
an opportunity for cultivation of H. isora in small-holder teak plantations in
Indonesia, with harvest of H. isora fruits as well as the medicinal bark.
PMID- 29944893
TI - Methamphetamine alters DNMT and HDAC activity in the posterior dorsal medial
amygdala in an ovarian steroid-dependent manner.
AB - Methamphetamine (Meth) is a psychomotor stimulant associated with increased
sexual drive and risky sexual behaviors in both men and women. Females are
comparatively understudied, despite the fact that are just as likely as men to
use methamphetamine. Importantly, Meth-associated sexual behaviors put female
users at a greater risk for unplanned pregnancies, and increase the risk of
psychiatric co-morbidities such as depression. Our work in a rodent model has
demonstrated that in the presence of the ovarian steroids, estradiol (EB) and
progesterone (P), methamphetamine facilitates the activation of neurons of in the
Medial Amygdala (MePD) and Ventromedial Nucleus of the Hypothalamus (VMN), nuclei
that are integral to female sexual behavior. As methamphetamine has been
previously associated with epigenetic changes in males, we hypothesized that
methamphetamine may facilitate sexual motivation in females by modulating the
amount of epigenetic enzymatic activity in the VMN and MePD. To test this
hypothesis, histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity
was quantitated in both the VMN and MePD in the presence and absence of
methamphetamine in femalerats who were ovariectomized (OVX), or OVXed and hormone
replaced with EB + P. DMNT1 and DNMT3B protein levels were also assessed. Our
results show that methamphetamine alters DNMT and HDAC activity in the MePD in an
ovarian steroid-dependent fashion. Both methamphetamine alone and EB + P alone
significantly reduce DNMT enzymatic activity in an OVX female, but do not further
decrease activity when both are given in combination. In contrast, no changes in
HDAC or DNMT activity were seen in the VMN regardless of treatment, but the
amount of DNMT3b after methamphetamine was significantly altered depending on the
presence or absence of ovarian steroids. Taken together, these results support
the hypothesis that methamphetamine induces change on an epigenetic level in
female rats in both a hormone and nucleus dependent manner, and suggests
epigenetic changes may play a role in methamphetamine's mechanism to facilitate
the sexual motivation.
PMID- 29944894
TI - Improving CPR quality with distributed practice and real-time feedback in
pediatric healthcare providers - A randomized controlled trial.
AB - OBJECTIVES: Guideline compliant CPR is associated with improved survival for
patients with cardiac arrest. Conventional Basic Life Support (BLS) training
results in suboptimal CPR competency and skill retention. We aimed to compare the
effectiveness of distributed CPR training with real-time feedback to conventional
BLS training for CPR skills in pediatric healthcare providers. METHODS:
Healthcare providers were randomized into receiving annual BLS training (control)
or distributed training with real-time feedback (intervention). The intervention
group was asked to practice CPR for 2 min on mannequins while receiving real-time
CPR feedback, at least once per month. Control group participants were not asked
to practice CPR during the study period. Excellent CPR was defined as 90%
guideline-compliance for depth, rate and recoil of chest compressions. CPR
performance of participants was assessed (on infant and adult-sized mannequins)
every 3 months for a duration of 12 months. CPR performance was compared between
the 2 groups. RESULTS: A total of 87 healthcare providers were included in the
analyses (control n = 41, intervention n = 46). Baseline assessment showed no
significant difference in CPR performance across the 2 groups. The intervention
group has a significantly greater proportion of participants with excellent CPR
compared with the control group on an adult sized mannequin (14.6% vs. 54.3%, p <
0.001) and infant-sized mannequin (19.5% vs. 71.7%, p < 0.001) at the end of the
study. In the intervention group, all CPR metrics except infant depth were
improved and retained over the course of the study. CONCLUSION: Distributed CPR
training with real-time feedback improves the compliance of AHA guidelines of
quality of CPR.
PMID- 29944895
TI - Cembrane-type diterpenoids from Macaranga pustulata.
AB - Three new cembrane-type diterpenoids, deheiculatins M-O (1-3), together with five
known analogues (4-8), were isolated from the twigs of Macaranga pustulata King
ex Hook. The structures of new compounds 1-3 were elucidated by extensive
spectroscopic analyses, modified Mosher's method, and the experimental and
calculated electronic circular dichroism (ECD) experiments. All the isolates were
evaluated for their cytotoxicity on three human cancer cell lines (CNE1, CNE2,
and HCT 116), and all of them showed weak cytotoxicity (IC50 > 20 MUM).
PMID- 29944897
TI - P2X2 Receptor Deficiency in Mouse Vestibular End Organs Attenuates Vestibular
Function.
AB - P2X2 receptors are ligand-gated cation channels activated by extracellular ATP
that modulate neural transmission in various neuronal systems. Although the
function and distribution of P2X2 receptors in the cochlea portion of the inner
ear are well established, their physiological role in the vestibular portion is
still not understood. Therefore, we investigated P2X2 receptor localization in
the peripheral vestibular portion, and assessed their physiological function in
vivo using P2X2 receptor knock out (P2X2-KO) mice. Histological analysis revealed
that P2X2 receptors were localized on the epithelial surface of supporting and
transitional cells of the vestibular end organs. To examine vestibular function
in P2X2-KO mice, we conducted behavioral tests and tested the vestibulo-ocular
reflex (VOR) during sinusoidal rotations. P2X2-KO mice exhibited significant
motor balance impairment in the balance beam test. VOR gain in P2X2-KO mice was
significantly reduced, with no decrease in the optokinetic response. In
conclusion, we showed that P2X2 receptors are mainly localized in the supporting
cells of the vestibular inner ear, and the loss of P2X2 receptors causes mild
vestibular dysfunction. Taken together, our findings suggest that the P2X2
receptor plays a modulatory role in vestibular function.
PMID- 29944896
TI - Human cathepsins K, L, and S: Related proteases, but unique fibrinolytic
activity.
AB - BACKGROUND: Fibrin formation and dissolution are attributed to cascades of
protease activation concluding with thrombin activation, and plasmin proteolysis
for fibrin breakdown. Cysteine cathepsins are powerful proteases secreted by
endothelial cells and others during cardiovascular disease and diabetes. Their
fibrinolytic activity and putative role in hemostasis has not been well
described. METHODS: Fibrin gels were polymerized and incubated with recombinant
human cathepsins (cat) K, L, or S, or plasmin, for dose-dependent and time
dependent studies. Dissolution of fibrin gels was imaged. SDS-PAGE was used to
resolve cleaved fragments released from fibrin gels and remnant insoluble fibrin
gel that was solubilized prior to electrophoresis to assess fibrin alpha, beta,
and gamma polypeptide hydrolysis by cathepsins. Multiplex cathepsin zymography
determined active amounts of cathepsins remaining. RESULTS: There was significant
loss of alpha and beta fibrin polypeptides after incubation with cathepsins, with
catS completely dissolving fibrin gel by 24 h. Binding to fibrin stabilized catL
active time; it associated with cleaved fibrin fragments of multiple sizes. This
was not observed for catK or S. CatS also remained active for longer times during
fibrin incubation, but its association/binding did not withstand SDS-PAGE
preparation. CONCLUSIONS: Human cathepsins K, L, and S are fibrinolytic, and
specifically can degrade the alpha and beta fibrin polypeptide chains, generating
fragments unique from plasmin. GENERAL SIGNIFICANCE: Demonstration of cathepsins
K, L, and S fibrinolytic activity leads to further investigation of contributory
roles in disrupting vascular hemostasis, or breakdown of fibrin-based engineered
vascular constructs where non-plasmin mediated fibrinolysis must be considered.
PMID- 29944898
TI - Increased antiviral capacity of transgenic silkworm via knockdown of multiple
genes on Bombyx mori bidensovirus.
AB - Bombyx mori bidensovirus (BmBDV) causes fatal flacherie disease leading to severe
economic losses in sericultures. The BmDNV-Z genome contains two single-stranded
DNA molecules, VD1 and VD2. For generating silkworm lines with antiviral
properties, two transgenic RNA interference (RNAi) vectors were constructed. Open
reading frames (ORFs) 1-4 of VD1 were knockdown by vector pb-BDV1 while ORF1a,
ORF1b, and ORF3 of VD2 were knockdown by vector pb-BDV2. Transgenic silkworm
lines BDV1-I and BDV2-I were generated via RNAi microinjection. Mortality rates
of BDV1-I and BDV2-I were reduced by 45% and 39%, respectively, and quantitative
PCR showed that VD1 and VD2 contents in BDV1-I and BDV2-I were significantly
lower than in the non-transgenic line. However, economic traits showed no obvious
differences. Thus, knockdown of multiple BmDNV-Z genes provides strong resistance
to BDV1-I and BDV2-I lines, and these can be used in sericulture without
hampering silk production.
PMID- 29944900
TI - Future priorities of acute hospitals for surgical site infection surveillance in
England.
AB - BACKGROUND: Since the launch of the national Surgical Site Infection (SSI)
Surveillance Service in 1997, successive expansions of the programme provided
hospitals with increasing flexibility in procedures to target through
surveillance. Ensuring that the programme continues to meet hospitals' needs
remains essential. AIM: As a means to inform the future direction of the service,
a survey of all acute National Health Service trusts was undertaken to assess and
understand priorities for surveillance. METHODS: A web-based survey was
circulated to acute NHS trust infection control teams in England, asking them to
identify and rank (i) reasons for undertaking current SSI surveillance, (ii)
priority surgical categories for future SSI surveillance, and (iii) reasons for
prioritizing these categories. FINDINGS: Of the 161 trusts surveyed, 84 (52%)
responded. Assessment of quality of care was identified as the most common driver
for SSI surveillance activity. Considerable heterogeneity in priority areas was
observed, with 24 different surgical categories selected as top priority. Of the
procedures undertaken by 15 or more trusts, caesarean section (2.7), hip
replacement (2.8) and coronary artery bypass graft (2.9) were highest ranked. All
17 categories in the current surveillance programme were selected as a top
priority by one or more trusts. CONCLUSION: Whereas the majority of hospitals'
priorities for SSI surveillance are included in the current programme, the top
ranked priority, caesarean section, is not included. Given the diversity of
priority areas, maintaining a comprehensive spectrum of categories in the
national programme is essential to assist hospitals in addressing local
priorities.
PMID- 29944899
TI - Formulation predictive dissolution (fPD) testing to advance oral drug product
development: An introduction to the US FDA funded '21st Century BA/BE' project.
AB - Over the past decade, formulation predictive dissolution (fPD) testing has gained
increasing attention. Another mindset is pushed forward where scientists in our
field are more confident to explore the in vivo behavior of an oral drug product
by performing predictive in vitro dissolution studies. Similarly, there is an
increasing interest in the application of modern computational fluid dynamics
(CFD) frameworks and high-performance computing platforms to study the local
processes underlying absorption within the gastrointestinal (GI) tract. In that
way, CFD and computing platforms both can inform future PBPK-based in silico
frameworks and determine the GI-motility-driven hydrodynamic impacts that should
be incorporated into in vitro dissolution methods for in vivo relevance. Current
compendial dissolution methods are not always reliable to predict the in vivo
behavior, especially not for biopharmaceutics classification system (BCS) class
2/4 compounds suffering from a low aqueous solubility. Developing a predictive
dissolution test will be more reliable, cost-effective and less time-consuming as
long as the predictive power of the test is sufficiently strong. There is a need
to develop a biorelevant, predictive dissolution method that can be applied by
pharmaceutical drug companies to facilitate marketing access for generic and
novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far
ranging research program designed to integrate (1) in vivo studies in humans in
order to further improve the understanding of the intraluminal processing of oral
dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2)
advancement of in vitro methodologies that incorporates higher levels of in vivo
relevance and (3) computational experiments to study the local processes
underlying dissolution, transport and absorption within the intestines performed
with a new unique CFD based framework. Of particular importance is revealing the
physiological variables determining the variability in in vivo dissolution and GI
absorption from person to person in order to address (potential) in vivo BE
failures. This paper provides an introduction to this multidisciplinary project,
informs the reader about current achievements and outlines future directions.
PMID- 29944901
TI - Nicotine Reduction Strategy: State of the science and challenges to tobacco
control policy and FDA tobacco product regulation.
AB - Nicotine addiction is the proximate cause of disease and death from cigarette
smoking. In 1994, we proposed reducing the nicotine content of cigarettes to non
addicting levels to reduce the risk of youth becoming addicted smokers and
promoting quitting in established smokers. In 2009, the Family Smoking Prevention
and Tobacco Control Act provided the authority to FDA to reduce nicotine levels
as appropriate to benefit public health. Over the past 15 years, considerable
research has determined that nicotine reduction is feasible and safe, resulting
in reduced nicotine dependence with little evidence of compensatory over-smoking.
The availability of acceptable non-combusted form of nicotine would provide
support and enhance acceptability of nicotine reduction in tobacco. Most
recently, the FDA promulgated a nicotine-based regulatory framework, which
includes nicotine reduction combined with ready availability of noncombustible
nicotine products. Nicotine reduction could contribute to a virtual end to the
use of cigarette smoking, with enormous benefits to public health.
PMID- 29944902
TI - Managing nicotine without smoke to save lives now: Evidence for harm
minimization.
AB - Tobacco control has made strides in prevention and cessation, but deaths will not
decline rapidly without massive behavior change. Currently, inhaled smoke from
combusting tobacco is chiefly responsible for prematurely killing 7.2 million
people worldwide and 530,000 in the United States annually. An array of
noncombustible nicotine products (NNPs) has emerged and has disrupted the
marketplace. Saving lives more speedily will require societal acceptance of
locating a "sweet spot" within a three-dimensional framework where NNPs are
simultaneously: 1. Less toxic, 2. Appealing (can reach smokers at scale), and 3.
Satisfying (adequate nicotine delivery) to displace smoking. For this harm
minimization framework to eliminate smoking, a laser focus on "smoking control"
(not general tobacco control) is needed. By adopting these economically viable
NNPs as part of the solution, NNPs can be smoking control's valued ally.
Synthesis of the science indicates that policy and regulation can sufficiently
protect youth while speeding the switch away from smoking. Despite some risks of
nicotine dependence that can be mitigated but not eliminated, no credible
evidence counters the assertion that NNPs will save lives if they displace
smoking. But scientific evidence and advocacy has selectively exaggerated NNP
harms over benefits. Accurate communication is crucial to dispel the
misperception of NNPs harms and reassure smokers they can successfully replace
smoking cigarettes with NNPs. Saving more lives now is an attainable and
pragmatic way to call for alignment of all stakeholders and factions within
traditional tobacco control rather than perpetuate the unrealized and
unrealizable perfection of nicotine prohibition.
PMID- 29944903
TI - Ageing at the level of telomeres in association to residential landscape and air
pollution at home and work: a review of the current evidence.
AB - Studies suggest that leukocyte telomere length is an index of systemic ageing.
Here, we discuss telomere length as a marker of biological ageing in relation to
residential landscape (greenness), residential air pollution and work-related
exposures. Telomere lengths are memories of cumulative oxidative and inflammatory
stress, and show to have inverse associations with the risk of non-communicable
diseases. For this reason, telomeres are considered as markers of biological
ageing. Studies at birth, in children, young adulthood, and elderly show that
residential green space, lower traffic exposure and long-term lower exposure to
particulate air pollution are associated with longer telomeres. Work-related
exposures including exposure to toxic metals, polycyclic aromatic hydrocarbons
and particulate matter are associated with shorter telomeres for a given age. In
contrast to chronic exposures, evidence is present of the observation that recent
exposure is associated with longer telomeres. Our overview shows that the
magnitude of residential and work-related environmental factors on telomere
length are often as important as many classical lifestyle factors.
PMID- 29944904
TI - Advanced in vitro models of vascular biology: Human induced pluripotent stem
cells and organ-on-chip technology.
AB - The vascular system is one of the first to develop during embryogenesis and is
essential for all organs and tissues in our body to develop and function. It has
many essential roles including controlling the absorption, distribution and
excretion of compounds and therefore determines the pharmacokinetics of drugs and
therapeutics. Vascular homeostasis is under tight physiological control which is
essential for maintaining tissues in a healthy state. Consequently, disruption of
vascular homeostasis plays an integral role in many disease processes, making
cells of the vessel wall attractive targets for therapeutic intervention.
Experimental models of blood vessels can therefore contribute significantly to
drug development and aid in predicting the biological effects of new drug
entities. The increasing availability of human induced pluripotent stem cells
(hiPSC) derived from healthy individuals and patients have accelerated advances
in developing experimental in vitro models of the vasculature: human endothelial
cells (ECs), pericytes and vascular smooth muscle cells (VSMCs), can now be
generated with high efficiency from hiPSC and used in 'microfluidic chips' (also
known as 'organ-on-chip' technology) as a basis for in vitro models of blood
vessels. These near physiological scaffolds allow the controlled integration of
fluid flow and three-dimensional (3D) co-cultures with perivascular cells to
mimic tissue- or organ-level physiology and dysfunction in vitro. Here, we review
recent multidisciplinary developments in these advanced experimental models of
blood vessels that combine hiPSC with microfluidic organ-on-chip technology. We
provide examples of their utility in various research areas and discuss steps
necessary for further integration in biomedical applications so that they can be
contribute effectively to the evaluation and development of new drugs and other
therapeutics as well as personalized (patient-specific) treatments.
PMID- 29944905
TI - HOTAIR is a REST-regulated lncRNA that promotes neuroendocrine differentiation in
castration resistant prostate cancer.
AB - Long non-coding RNAs (lncRNAs) are emerging as novel diagnostic markers of
prostate cancer (PCa) and new determinants of castration-resistant PCa (CRPC), an
aggressive and metastatic form of PCa. In addition to androgen receptor (AR)
signaling, neuroendocrine differentiation (NED) is associated with CRPC. Recent
reports demonstrate that the downregulation of repressor element-1 silencing
transcription factor (REST) protein is a key step in NED of PCa cells. Here, we
report HOTAIR as a novel REST-repressed lncRNA that is upregulated in NED PCa
cells and in CRPC. HOTAIR overexpression is sufficient to induce, whereas
knockdown of HOTAIR suppressed NED of PCa cells. Gene ontology (GO) analysis of
differentially expressed genes under HOTAIR overexpression and in CRPC versus
benign prostatic hyperplasia (BPH) suggests that HOTAIR may participate in PCa
progression. Taken together, our results provide the first evidence of lncRNA
HOTAIR as a driver for NED of PCa cells.
PMID- 29944906
TI - Novel combined Ato-C treatment synergistically suppresses proliferation of Bcr
Abl-positive leukemic cells in vitro and in vivo.
AB - Chronic myelogenous leukemia (CML) accounts for 15-20% of all leukemias affecting
adults. Despite recent advances in the development of specific Bcr-Abl tyrosine
kinase inhibitors (TKIs), some CML patients suffer from relapse due to TKI
resistance. Here, we assessed the efficacy of a novel combinatorial arsenic
trioxide (ATO) and cisplatin (CDDP) treatment (Ato-C) in human Bcr-Abl-positive
leukemic cells. Combination index analyses revealed that a synergistic
interaction of ATO and CDDP elicits a wide range of effects in K562, KU-812, MEG
A2, and KCL-22 cells. Notably, Ato-C synergistically enhanced apoptosis and
decreased the survival of both acquired TKI-resistant CML cells and the cells
expressing mutant Bcr-AblT315I. In addition, Ato-C dramatically decreased the
phosphorylation level of forkhead transcription factor FOXO1/3a and STAT5 as well
as c-Myc protein level. Interestingly, results of gene set enrichment analysis
showed that Ato-C significantly downregulates the expression of MYC- and/or E2F1
target genes. Furthermore, Ato-C significantly suppressed the proliferation of
MEG-A2-derived tumor when compared with that following monotherapy in vivo.
Collectively, these results suggest that combined Ato-C treatment could be a
promising alternative to the current therapeutic regime in CML.
PMID- 29944907
TI - Detection of tobamoviruses by RT-PCR using a novel pair of degenerate primers.
AB - A generic RT-PCR assay was developed for the universal detection of viruses of
the genus Tobamovirus using a novel pair of degenerate primers designed based on
conserved regions on replicase genes of 32 tobamoviruses. The assay detected nine
tobamoviruses, including six Solanaceae-infecting subgroup tobamoviruses of
Tobacco mosaic virus (TMV), Tomato mosaic virus (ToMV), Tomato mottle mosaic
virus (ToMMV), Tobacco mottle green mosaic virus (TMGMV), Pepper mild mottle
virus (PMMoV), Paprika mild mottle virus (PaMMV), one Orchidaceae-infecting
tobamovirus of Odontoglossum ringspot virus (ORSV) and two Cucurbitaceae
infecting subgroup tobamoviruses of Cucumber green mottle mosaic virus (CGMMV)
and Zucchini green mottle mosaic virus (ZGMMV), with high amplification
efficiency, specificity and sensitivity. The assay was applied to detect
tobamoviruses in pepper and tomato fields. Five tobamoviruses, PMMoV, TMV, ToMV,
ToMMV and TMGMV, were detected from the pepper fields in single and mixed
infections. Single infections of PMMoV, ToMV and ToMMV and mix-infection of ToMV
+ PMMoV were detected from the tomato fields. Among these viruses, PMMoV was
first detected from tomato worldwide, while ToMMV was first detected from tomato
plants in China. This generic assay is simple, cost-effective and has great
potential to detect more tobamoviruses in the field.
PMID- 29944908
TI - Gratitude intervention modulates P3 amplitude in a temporal discounting task.
AB - Gratitude has been shown to reduce economic impatience. In particular,
individuals induced to experience heightened gratitude are more willing to choose
delayed larger rewards over immediate smaller rewards (i.e., they have lower
discounting rates) than those in a neutral condition. Using the event-related
potential (ERP) method, we investigated the relation between gratitude level and
neurophysiological correlates. Of interest was motivated information processing,
as indexed by the P3 component. Participants were administered a gratitude or a
neutral mood induction followed by a temporal discounting task (choosing between
a fixed immediate reward versus a future reward that varied across trials) while
electroencephalogram (EEG) activity was recorded. Individuals in the gratitude
condition had greater P3 amplitude, suggesting greater attention to the future
reward option (the choice option that varied across trials), even when this
option was not selected, and providing the first evidence of gratitude-induced
changes in electrophysiological activity.
PMID- 29944909
TI - Genetic and phenotypic features defining industrial relevant Lactococcus lactis,
L. cremoris and L. lactis biovar. diacetylactis strains.
AB - Lactococcus lactis strains constitute one of the most important starter cultures
for cheese production. In this study, a genome-wide analysis was performed
including 68 available genomes of L. lactis group strains showing the existence
of two species (L. lactis and L. cremoris) and two biovars (L. lactis biovar.
diacetylactis and L. cremoris biovar. lactis). The proposed classification scheme
revealed coherency among phenotypic (through in silico and in vivo bacterial
function profiling), phylogenomic (through maximum likelihood trees) and genomic
(using overall genome sequence-based parameters) approaches. Strain biodiversity
for the industrial biovar. diacetylactis was also analyzed, finding they are
formed by at least three variants with the CC1 clonal complex as the only one
distributed worldwide. These findings and methodologies will help improve the
selection of L. lactis group strains for industrial use as well as facilitate the
interpretation of previous or future research studies on this diverse group of
bacteria.
PMID- 29944910
TI - Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced
disruption of pup retrieval on an elevated plus maze, but has no effect on D2
blockade-induced one.
AB - Appetitive aspect of rat maternal behavior, such as pup retrieval, is
motivationally driven and sensitive to dopamine disturbances. Activation or
blockade of dopamine D2 receptors causes a similar disruption of pup retrieval,
which may also reflect an increase in maternal anxiety and/or a disruption of
executive function. Recent work indicates that serotonin 5-HT2A receptors also
play an important role in rat maternal behavior. Given the well-known modulation
of 5-HT2A on the mesolimbic and mesocortical dopamine functions, the present
study examined the extent to which blockade of 5-HT2A receptors on dopamine D2
mediated maternal effects using a pup retrieval on the elevated plus maze (EPM)
test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole
(a D2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D2 antagonist, 0.1 or
0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT2A receptor antagonist, 1.0
mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and
tested at 30, 90 and 240 min after quinpirole or haloperidol injection on
postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup
retrieved (an index of maternal motivation) and sequential retrieval score (an
index of executive function), prolonged the pup retrieval latencies, reduced the
percentage of time spent on the open arms (an index of maternal anxiety), and
decreased the distance travelled on the maze in a dose-dependent and time
dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval,
but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no
effect on the haloperidol-induced one. These findings suggest a complex
interactive effect between 5-HT2A and D2 receptors on one or several maternal
processes (maternal motivation, anxiety and executive function), and support the
idea that one molecular mechanism by which 5-HT2A receptors mediate maternal
behavior is through its modulation of D2 receptors.
PMID- 29944911
TI - Cell death cascade and molecular therapy in ADAR2-deficient motor neurons of ALS.
AB - TAR DNA-binding protein (TDP-43) pathology in the motor neurons is the most
reliable pathological hallmark of amyotrophic lateral sclerosis (ALS), and motor
neurons bearing TDP-43 pathology invariably exhibit failure in RNA editing at the
GluA2 glutamine/arginine (Q/R) site due to down-regulation of adenosine deaminase
acting on RNA 2 (ADAR2). Conditional ADAR2 knockout (AR2) mice display ALS-like
phenotype, including progressive motor dysfunction due to loss of motor neurons.
Motor neurons devoid of ADAR2 express Q/R site-unedited GluA2, and AMPA receptors
with unedited GluA2 in their subunit assembly are abnormally permeable to Ca2+,
which results in progressive neuronal death. Moreover, analysis of AR2 mice has
demonstrated that exaggerated Ca2+ influx through the abnormal AMPA receptors
overactivates calpain, a Ca2+-dependent protease, that cleaves TDP-43 into
aggregation-prone fragments, which serve as seeds for TDP-43 pathology. Activated
calpain also disrupts nucleo-cytoplasmic transport and gene expression by
cleaving molecules involved in nucleocytoplasmic transport, including
nucleoporins. These lines of evidence prompted us to develop molecular targeting
therapy for ALS by normalization of disrupted intracellular environment due to
ADAR2 down-regulation. In this review, we have summarized the work from our group
on the cell death cascade in sporadic ALS and discussed a potential therapeutic
strategy for ALS.
PMID- 29944912
TI - Dynamic Pelvic Magnetic Resonance Imaging Evaluation of Pelvic Organ Prolapse
Compared to Physical Examination Findings.
AB - OBJECTIVE: To compare dynamic magnetic resonance imaging (dMRI) defecography
phase findings with physical examination (PE) grading in the evaluation of pelvic
organ prolapse (POP). METHODS: We retrospectively reviewed 274 consecutive
patients who underwent dMRI with defecography. Baden-Walker grading of POP,
absolute dMRI values, and grading by dMRI were collected for anterior, apical,
and posterior compartments. Anatomically significant POP on PE was defined as
Baden-Walker Grade >=3 and on dMRI by dMRI Grade >=2. A Spearman's Rank
correlation was performed between absolute dMRI values and respective POP grades.
RESULTS: A total of 178 female patients were included. Anatomically insignificant
and significant cystoceles had a 26.4% (19/72) and 84.6% (66/78) agreement
respectively. Anatomically insignificant and significant apical prolapse had a
2.0% (2/100) and 62.9% (17/27) agreement respectively. Anatomically insignificant
and significant posterior prolapse had a 49.5% (51/103) and 78.7% (59/75)
agreement respectively. PE detected only 30% (9/30) of total dMRI detected
enteroceles and misdiagnosed 10% (3/30) of these patients with a rectocele.
CONCLUSION: The dMRI defecography phase correlated well for anatomically
significant prolapse in anterior and posterior compartments. dMRI was superior to
PE for enterocele detection and was better able to distinguish an enterocele from
a rectocele. Thus, dMRI may have the greatest diagnostic value in cases where the
presence of an enterocele is unclear in apical and/or posterior compartments.
PMID- 29944913
TI - Methamphetamine toxicity-induced calcineurin activation, nuclear translocation of
nuclear factor of activated T-cells and elevation of cyclooxygenase 2 levels are
averted by calpastatin overexpression in neuroblastoma SH-SY5Y cells.
AB - Methamphetamine (METH) is an addictive stimulant drug that has many negative
consequences, including toxic effects to the brain. Recently, the induction of
inflammatory processes has been identified as a potential contributing factor to
induce neuronal cell degeneration. It has been demonstrated that the expression
of inflammatory agents, such as cyclooxygenase 2 (COX-2), depends on the
activation of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT).
Moreover, the excessive elevation in cytosolic Ca2+ levels activates the cell
death process, including calpain activation in neurons, which was diminished by
the overexpression of the calpain inhibitor protein, calpastatin. However, it is
unclear whether calpain mediates CaN-NFAT activation in the neurotoxic process.
In the present study, we observed that the toxic high dose of METH-treated
neuroblastoma SH-SY5Y cells significantly decreased cell viability but increased
apoptotic cell death, the active cleaved form of calcineurin, the nuclear
translocation of NFAT, and COX-2 levels. Nevertheless, these toxic effects were
diminished in METH-treated calpastatin-overexpressing SH-SY5Y cells. These
findings might emphasize the role of calpastatin against METH-induced toxicity by
a mechanism related to calpain-dependent CaN-NFAT activation-induced COX-2
expression.
PMID- 29944914
TI - Arsenic-induced apoptosis in the p53-proficient and p53-deficient cells through
differential modulation of NFkB pathway.
AB - Arsenic is a well-known environmental carcinogen and an effective
chemotherapeutic agent. The underlying mechanism of this dual-effect, however, is
not fully understood. In this study, we applied mouse p53+/+ and p53-/- cells to
examine the NFkappaB pathway and proinflammatory cytokines after arsenic
treatment. Arsenic reduced cell viability and increased more apoptosis in the p53
/- cells as compared to p53+/+ cells, which was correlated with activation of
SAPK/JNK, p38 MAPK, and AKT pathways. A transcriptional regulatory network
analysis revealed that arsenic activated transcription regulatory elements E2F,
Egr1, Trp53, Stat6, Bcl6, Creb2 and ATF4 in the p53+/+ cells, while in the p53-/-
cells, arsenic treatment altered transcription factors NFkappaB, Pparg, Creb2,
ATF4, and Egr1. We observed dynamic changes in phosphorylated NFkappaB p65 (p
NFkappaB p65) and phosphorylated IKKalphabeta (p-IKKalphabeta) in both genotypes
from 4 h to 24 h after treatment, significant decreases of p-NFkappaB p65 and p
IKKalphabeta in the p53-/- cells, whereas increases of p-NFkappaB p65 and p
IKKalphabeta were observed in the p53+/+ cells. Our study confirmed the
differential modulation of NFkappaB pathway by arsenic in the p53+/+ or p53-/-
cells and this observation of the differential mechanism of cell death between
the p53+/+ and p53-/- cells might be linked to the unique ability of arsenic to
act as both a carcinogen and a chemotherapeutic agent.
PMID- 29944915
TI - Acute and long-lasting cortical thickness changes following intensive first
person action videogame practice.
AB - Recent evidence shows how an extensive gaming experience might positively impact
cognitive and perceptual functioning, leading to brain structural changes
observed in cross-sectional studies. Importantly, changes seem to be game
specific, reflecting gameplay styles and therefore opening to the possibility of
tailoring videogames according to rehabilitation and enhancement purposes.
However, whether if such brain effects can be induced even with limited gaming
experience, and whether if they can outlast the gaming period, is still unknown.
Here we quantified both cognitive and grey matter thickness changes following 15
daily gaming sessions based on a modified version of a 3D first-person shooter
(FPS) played in laboratory settings. Twenty-nine healthy participants were
randomly assigned to a control or a gaming group and underwent a cognitive
assessment, an in-game performance evaluation and structural magnetic resonance
imaging before (T0), immediately after (T1) and three months after the end of the
experiment (T2). At T1, a significant increase in thickness of the bilateral
parahippocampal cortex (PHC), somatosensory cortex (S1), superior parietal lobule
(SPL) and right insula were observed. Changes in S1 matched the hand
representation bilaterally, while PHC changes corresponded to the parahippocampal
place area (PPA). Surprisingly, changes in thickness were still present at T2 for
S1, PHC, SPL and right insula as compared to T0. Finally, surface-based
regression identified the lingual gyrus as the best predictor of changes in game
performance at T1. Results stress the specific impact of core game elements, such
as spatial navigation and visuomotor coordination on structural brain properties,
with effects outlasting even a short intensive gaming period.
PMID- 29944917
TI - Molecular Networks Regulating Meristem Homeostasis.
PMID- 29944916
TI - Two Cockayne Syndrome patients with a novel splice site mutation - clinical and
metabolic analyses.
AB - Cockayne Syndrome (CS) is a rare autosomal recessive disorder, which leads to
neurodegeneration, growth failure and premature aging. Most of the cases are due
to mutations in the ERCC6 gene, which encodes the protein CSB. CSB is involved in
several functions including DNA repair and transcription. Here we describe two
Danish brothers with CS. Both patients carried a novel splice site mutation
(c.2382+2T>G), and a previously described nonsense mutation (c.3259C>T,
p.Arg1087X) in a biallelic state. Both patients presented the cardinal features
of the disease including microcephaly, congenital cataract and postnatal growth
failure. In addition, their fibroblasts were hypersensitive to UV irradiation and
exhibited increased superoxide levels in comparison to fibroblasts from healthy
age and gender matched individuals. Metabolomic analysis revealed a distinctive
metabolic profile in cells from the CS patients compared to control cells. Among
others, alpha-ketoglutarate, hydroxyglutarate and certain amino acids (ornithine,
proline and glycine) were reduced in the CS patient fibroblasts, whereas
glycolytic intermediates (glucose-6-phosphate and pyruvic acid) and fatty acids
(palmitic, stearic and myristic acid) were increased. Our data not only provide
additional information to the database of CS mutations, but also point towards
targets for potential treatment of this devastating disease.
PMID- 29944918
TI - More Ways to Skin the Proverbial Cat.
PMID- 29944920
TI - Draft genome sequence of a blaCMY-2/IncI1-harbouring Escherichia coli D:ST457
isolated from coastal benthic organisms.
AB - OBJECTIVES: Marine bivalves can act as bioindicators of marine environment
pollution by multidrug-resistant (MDR) enteric bacteria of medical interest. The
aim of this study was to report the draft genome sequence of a plasmid-encoded
AmpC (pAmpC) (CMY-2)-carrying Escherichia coli isolate recovered from a marine
bivalve sample in the coastal shore of Southeast Brazil. METHODS: The whole
genome was sequenced on an Illumina NextSeq platform and was assembled using
Velvet v.1.2.10. Data analysis was carried out using tools available from the
Center of Genomic Epidemiology and Geneious R10 software. RESULTS: The genome
size was calculated at 5198055bp, comprising a total of 5316 protein-coding
sequences. The strain was assigned to ST457 and presented the blaCMY-2 pAmpC
gene. In addition, the strain was clustered into the pathogenic phylogenetic
group D. CONCLUSION: The release of this draft genome sequence can provide
valuable information to better understand the dissemination of MDR enteric
bacteria in marine environments.
PMID- 29944921
TI - Intrinsically disordered N-terminal domain of the Helicoverpa armigera
Ultraspiracle stabilizes the dimeric form via a scorpion-like structure.
AB - Nuclear receptors (NRs) are a family of ligand-dependent transcription factors
activated by lipophilic compounds. NRs share a common structure comprising three
domains: a variable N-terminal domain (NTD), a highly conserved globular DNA
binding domain and a ligand-binding domain. There are numerous papers describing
the molecular details of the latter two globular domains. However, very little is
known about the structure-function relationship of the NTD, especially as an
intrinsically disordered fragment of NRs that may influence the molecular
properties and, in turn, the function of globular domains. Here, we investigated
whether and how an intrinsically disordered NTD consisting of 58 amino acid
residues affects the functions of the globular domains of the Ultraspiracle
protein from Helicoverpa armigera (HaUsp). The role of the NTD was examined for
two well-known and easily testable NR functions, i.e., interactions with specific
DNA sequences and dimerization. Electrophoretic mobility shift assays showed that
the intrinsically disordered NTD influences the interaction of HaUsp with
specific DNA sequences, apparently by destabilization of HaUsp-DNA complexes. On
the other hand, multi-angle light scattering and sedimentation velocity
analytical ultracentrifugation revealed that the NTD acts as a structural element
that stabilizes HaUsp homodimers. Molecular models based on small-angle X-ray
scattering indicate that the intrinsically disordered NTD may exert its effects
on the tested HaUsp functions by forming an unexpected scorpion-like structure,
in which the NTD bends towards the ligand-binding domain in each subunit of the
HaUsp homodimer. This structure may be crucial for specific NTD-dependent
regulation of the functions of globular domains in NRs.
PMID- 29944922
TI - Electromyography analysis and botulinum toxin plan in a pianist with musician's
dystonia: A case report.
PMID- 29944919
TI - The dynamic receptive fields of retinal ganglion cells.
AB - Retinal ganglion cells (RGCs) were one of the first classes of sensory neurons to
be described in terms of a receptive field (RF). Over the last six decades, our
understanding of the diversity of RGC types and the nuances of their response
properties has grown exponentially. We will review the current understanding of
RGC RFs mostly from studies in mammals, but including work from other vertebrates
as well. We will argue for a new paradigm that embraces the fluidity of RGC RFs
with an eye toward the neuroethology of vision. Specifically, we will focus on
(1) different methods for measuring RGC RFs, (2) RF models, (3) feature
selectivity and the distinction between fluid and stable RF properties, and (4)
ideas about the future of understanding RGC RFs.
PMID- 29944923
TI - Descriptive pilot study of vividness and temporal equivalence during motor
imagery training after quadriplegia.
AB - BACKGROUND: Motor imagery (MI) training is often used to improve physical
practice (PP), and the functional equivalence between imagined and practiced
movements is widely considered essential for positive training outcomes.
OBJECTIVE: We previously showed that a 5-week MI training program improved
tenodesis grasp in individuals with C6-C7 quadriplegia. Here we investigated
whether functional equivalence changed during the course of this training
program. METHODS: In this descriptive pilot study, we retrospectively analyzed
data for 6 individuals with C6-C7 quadriplegia (spinal cord injured [SCI]) and 6
healthy age-matched controls who trained for 5 weeks in visual and kinesthetic
motor imagery or visualization of geometric shapes (controls). Before training,
we assessed MI ability by using the Kinesthetic and Visual Imagery Questionnaire
(KVIQ). We analyzed functional equivalence by vividness measured on a visual
analog scale (0-100) and MI/PP time ratios computed from imagined and physically
practiced movement durations measured during MI training. These analyses were re
run considering that half of the participants with quadriplegia were good imagers
and the other half were poor imagers based on KVIQ scores. To investigate
generalization of training effects, we analyzed MI/PP ratios for an untrained
pointing task before (3 baseline measures), immediately after, and 2 months after
training. RESULTS: During MI training, imagery vividness increased significantly.
Only the good imagers evolved toward temporal equivalence during training. Good
imagers were also the only participants who showed changes in temporal
equivalence on the untrained pointing task. CONCLUSION: This is the first study
reporting improvement in functional equivalence during an MI training program
that improved tenodesis grasp in individuals with C6-C7 quadriplegia. We
recommend that clinical MI programs focus primarily on vividness and suggest that
feedback about movement duration could potentially improve temporal equivalence,
which could in turn lead to further improvement in PP.
PMID- 29944925
TI - Would a Placebo Acupuncture Needle be Able to Induce Deqi?
AB - The aim of this study was to evaluate Deqi in patients under treatment with
acupuncture and sham acupuncture. Forty (40) volunteers of all genders with
temporomandibular dysfunction (TMD) were randomized into two study groups:
Acupuncture and Sham Acupuncture (non-penetrating device). The patients answered
the Southampton Needle Sensation Questionnaire (SNSQ) at the initial and final
sessions of acupuncture treatment. The questionnaire was composed of two parts:
the first one, consisting of 17 Deqi descriptors and a Likert scale in order to
evaluate the intensity of each sensation; and the second one, consisting of a
visual analog scale (VAS) to evaluate how painful the acupuncture treatment was.
At the initial session, LI4 was the most cited acupuncture point in both groups,
being responsible for a 'Slight Intensity' needling sensation of electric shock
in the acupuncture group at initial (10%) and final (15%) sessions. The most
common related needling sensations at different acupuncture points was "Pricking"
and "Sharp" in both groups. The acupuncture group showed higher VAS than the Sham
Acupuncture either in the initial (3.87 * 2.43) and final (2.04 * 2.14) sessions.
Deqi response to acupuncture stimulation was verified either in the both groups.
PMID- 29944924
TI - Mitochondria in health and disease.
AB - Mitochondrial biology has become an area of intense research owing to the unique
physiology of the organelle and its role in several types of cancers and other
disorders. It has been found that mitochondria-encoded proteins, mitochondrial
DNA and even RNA influence the functioning of the cell in more ways than were
previously imagined. This may contribute to disease phenotypes which require
detailed investigation and communication to the community health care providers.
Additionally, this provides several novel avenues in drug designing against
various cancers, neurodegenerative diseases and other metabolic disorders. The
sixth annual conference of the Society for Mitochondrial Research and Medicine -
India (SMRM) titled, 'Mitochondria in Health and Disease' was organized by Rana
P. Singh at the School of Life Sciences, Jawaharlal Nehru University in New
Delhi, India from 10th to 11th February 2017. The underlying objective of the
conference was to provide a platform to discuss the recent advances in basic and
translational research in mitochondrial biology and diseases. The conference
aimed to translate academic research into clinical practice by providing a forum
for basic researchers and clinicians to share their knowledge and build
collaborations towards development of advanced therapeutic in mitochondrial
diseases. To facilitate the knowledge-sharing, six major themes for the
scientific sessions were (1) understanding of mitochondrial biology in disease
progression, (2) advances in basic and translational mitochondrial research, (3)
mitochondria in evolution and development, (4) targeting mitochondria for cancer
prevention and treatment, (5) mitochondria in metabolic and neurological
disorders and (6) mitochondria in stem cell and regeneration biology. This report
summarizes the major outcomes of the discussions at the conference.
PMID- 29944927
TI - Shape-memory collagen scaffold for enhanced cartilage regeneration: native
collagen versus denatured collagen.
AB - OBJECTIVE: Nowadays, it is still questionable whether denatured collagen (DCol)
can replace the native collagen (Col) as a bioactive protein in cartilage
engineering. We sought to study the advantages of Col with a triple-helical
structure in the collagen-based composite materials for cartilage engineering.
METHODS: We presented new three-dimensional (3D) Col and DCol scaffolds with
shape memory properties. The effects of Col and DCol scaffolds on rabbit
chondrocytes' proliferation, adhesion, differentiation and interaction with
matrix were investigated. Tissue compatibility was performed in a subcutaneous
Sprague Dawley (SD) rat model. The repair ability of different scaffolds with
chondrocytes for full-thickness articular cartilage defects in knee joints of New
Zealand white rabbits were investigated. RESULTS: The results indicated that the
Col scaffolds (with concentration 1.6wt% and 0.8wt%, respectively) promoted the
proliferation, adhesion and redifferentiation of chondrocytes, as well as
chondrocyte-matrix interaction, to a greater degree than the DCol scaffolds. In
the animal experiment, the Col scaffolds filled in the defect hole significantly
maintained chondrocytes function, promoted cartilage and subchondral bone
regeneration, compared with the DCol scaffolds, and the scaffolds loaded with
chondrocytes were better than the cell-free scaffolds, especially in the case of
the Col scaffolds (1.6 wt%). CONCLUSIONS: Taken together, these insights suggest
that the better proliferation, adhesion and redifferentiation of chondrocytes in
Col scaffolds with the triple-helical structure may contribute to the greater
cartilage repair ability. Col scaffolds may be more appropriate for repairing
cartilage defects than DCol scaffolds, and DCol cannot as an alternative when
using collagen-based materials for cartilage engineering applications.
PMID- 29944926
TI - Effect of Accelerated Infliximab Induction on Short- and Long-Term Outcomes of
Acute Severe Ulcerative Colitis: A Retrospective Multicenter Study and Meta
Analysis.
AB - BACKGROUND & AIMS: In patients with acute severe ulcerative colitis (ASUC),
standard infliximab induction therapy has modest efficacy. There are limited data
on the short-term or long-term efficacy of accelerated infliximab induction
therapy for these patients. METHODS: In a retrospective study, we collected data
from 213 patients with steroid refractory ASUC who received infliximab rescue
therapy at 3 centers, from 2005 through 2017. Patients were classified that
received standard therapy (5mg/kg infliximab at weeks 0, 2, and 6) or accelerated
therapy (>5mg/kg infliximab at shorter intervals). The primary outcome was
colectomy in-hospital and at 3, 6, 12, and 24 months. Multivariable regression
models were adjusted for relevant confounders. We also performed a meta-analysis
of published effects of standard vs accelerated infliximab treatment of ASUC.
RESULTS: In the retrospective analysis, 81 patients received accelerated
infliximab therapy and 132 received standard infliximab therapy. There were no
differences in characteristics between the groups, including levels of C-reactive
protein or albumin. Similar proportions of patients in each group underwent in
hospital colectomy (9% receiving accelerated therapy vs 8% receiving standard
therapy; adjusted odds ratio, 1.35; 95% CI, 0.38-4.82). There was no significant
difference between groups in proportions that underwent colectomy at 3, 6, 12, or
24 months (P > .20 for all comparisons). Among those in the accelerated group, an
initial dose of 10 mg/kg was associated with a lower rate of colectomy compared
to patients who initially received 5 mg/kg followed by subsequent doses of 5mg/kg
or higher. Our systematic review identified 7 studies (181 patients receiving
accelerated infliximab and 436 receiving standard infliximab) and found no
significant differences in short- or long-term outcomes. CONCLUSION: In a
retrospective study and meta-analysis, we found no association between
accelerated infliximab induction therapy and lower rates of colectomy in patients
with ASUC, compared to standard induction therapy. However, confounding by
disease severity cannot be excluded. Randomized trials are warranted to compare
these treatment strategies.
PMID- 29944928
TI - Neutralization of macrophage migration inhibitory factor improves host survival
after Clostridium difficile infection.
AB - Clostridium difficile is an important cause of nosocomial diarrhea in the western
world. Toxins (A, B, and binary toxins) generated by C. difficile bacteria damage
intestinal epithelial cells. Hallmarks of host response to C. difficile infection
(CDI) include upregulation of inflammatory mediators and tissue infiltration by
immune cells. Macrophage migration inhibitory factor (MIF) is an inflammatory
cytokine that is known to enhance the host immune response to infectious
pathogens. Additionally, MIF can adversely impact host survival to numerous
infections. The role of MIF in the pathogenesis of CDI remains poorly understood.
Here, we show that patients with CDI had significantly higher circulating MIF
compared to patients who had diarrhea but tested negative for C. difficile (non
CDI controls). Similarly, in a mouse model, C. difficile challenge significantly
increased levels of plasma and tissue MIF. Antibody-mediated depletion of MIF
decreased C. difficile-induced inflammatory responses, clinical disease, and
mortality. Together, these results uncover a potential role for MIF in
exacerbating CDI and suggest that use of anti-MIF antibodies may represent a
therapeutic strategy to curb host inflammatory responses and improve disease
outcomes in CDI.
PMID- 29944929
TI - Paracoccidioidomycosis diagnosed in bone marrow biopsy: Indicative of fungemia
and unfavorable prognosis.
PMID- 29944930
TI - Recurrence of tuberculosis among patients following treatment completion in eight
provinces of Vietnam: A nested case-control study.
AB - BACKGROUND: Patients completing treatment for tuberculosis (TB) in high
prevalence settings face a risk of developing recurrent disease. This has
important consequences for public health, given its association with drug
resistance and a poor prognosis. Previous research has implicated individual
factors such as smoking, alcohol use, HIV, poor treatment adherence, and drug
resistant disease as risk factors for recurrence. However, little is known about
how these factors co-act to produce recurrent disease. Furthermore, perhaps
factors related to the index disease means higher burden/low resource settings
may be more prone to recurrent disease that could be preventable. METHODS: We
conducted a case-control study nested within a cohort of consecutively enrolled
adults who were being treated for smear positive pulmonary TB in 70 randomly
selected district clinics in Vietnam. Cases were patients with recurrent TB,
identified by follow-up from the parent cohort study. Controls were selected from
the cohort by random sampling. Information on demographic, clinical and disease
related characteristics was obtained by interview. Treatment information was
extracted from clinic registries. Logistic regression, with stepwise selection,
was used to develop a fully adjusted model for the odds of recurrence of TB.
RESULTS: We recruited 10,964 patients between October 2010 and July 2013. Median
follow-up was 988 days. At the end of follow-up, 505 patients (4.7%) with
recurrence were identified as cases and 630 other patients were randomly selected
as controls. Predictors of recurrence included multidrug-resistant (MDR)-TB
(adjusted odds ratio 79.6; 95% CI: 25.1-252.0), self-reported prior TB therapy
(aOR=2.5; 95% CI: 1.7-3.5), and incomplete adherence (aOR=1.9; 95% CI 1.1-3.1).
CONCLUSIONS: Index disease treatment history is a leading determinant of relapse
among patients with TB in Vietnam. Further research is required to identify
interventions that will reduce the risk of recurrent disease and enhance its
early detection within high-risk populations.
PMID- 29944931
TI - Vaginal Repair of Cesarean Section Scar Diverticula Diagnosed in Nonpregnant
Women.
AB - STUDY OBJECTIVE: Cesarean section scar diverticulum (CSD) lead to many long-term
complications. CSD is more prevalent in patients with a retroflexed uterus than
in those with an anteflexed uterus. Therefore, we wanted to estimate the
association between flexion of the uterus and the outcome of treatment for CSD
treated by vaginal repair. DESIGN: Retrospective cohort study (Canadian Task
Force classification II-2). SETTING: University hospital. PATIENTS: A total of
241 women with a CSD were enrolled at the Shanghai First Maternity & Infant
Hospital between May 2014 and Oct 2016. INTERVENTIONS: Vaginal excision and
suture of CSD. MEASUREMENT AND MAIN RESULTS: A high failure rate was reported in
remodeling of the scar by other surgeries in women with retroflexed uteri.
Clinical information was obtained from medical records. Because intermenstrual
bleeding was a presenting symptom of CSD, duration of menstruation was compared
between groups. Patients were required to be followed at 1, 3, and 6 months to
record their menstruation situation and to measure the CSD. The thickness of the
residual myometrium (TRM) in the retroflexion group was much thinner than that in
the anteflexion group before treatment (2.5 +/- 1.2 mm vs 2.9 +/- 1.1 mm, p <
.05). There was no statistical difference in pretreatment menstruation duration
between groups (p > .05). The duration of menstruation in the anteflexion group
was 8.2 +/- 2.1 days and 8.5 +/- 2.1 days and in the retroflexion group was 7.6
+/- 2.0 days and 7.7 +/- 3.1 days at 3 and 6 months after surgery, respectively
(p < .05). In all 58.6% of patients (140/239) who had a retroflexed uterus, 60.0%
(84/140) reached <=7 days of menstruation at 6 months after surgery (p < .05).
Although about 40% patients still had CSD after repair, menstruation duration and
TRM were improved significantly (p < .05). CONCLUSION: We propose that vaginal
repair can relieve symptoms and improve TRM for CSD patients, especially for
those who have a retroflexed uterus. However, 40% of patients still had a defect
postoperatively.
PMID- 29944932
TI - Ultrasound Scoring of Endometrial Pattern for Fast-track Identification or
Exclusion of Endometrial Cancer in Women with Postmenopausal Bleeding.
AB - STUDY OBJECTIVE: To evaluate the risk of endometrial cancer (REC) scoring system
for the prediction of high and low probability of endometrial cancer (EC) in
women with postmenopausal bleeding (PMB). DESIGN: A prospective study (Canadian
Task Force classification II-1). SETTING: An academic hospital. PATIENTS: Nine
hundred fifty consecutive patients with PMB underwent transvaginal
ultrasonography (TVS) and REC scoring between November 2013 and December 2015.
INTERVENTIONS: Obstetrics and gynecology residents supervised by trained
physicians scored endometrial patterns according to the previously established
REC scoring system. The reference standard was endometrial samples, endometrial
thickness (ET, 4-4.9 mm), operative hysteroscopy or hysterectomy (ET >=5 mm), and
1-year follow-up in all patients presenting with ET <4 mm. Diagnostic performance
for the prediction of probability of malignancy was assessed using the REC
scoring system. MEASUREMENTS AND MAIN RESULTS: The area under the receiver
operating characteristic curve of the TVS REC scoring system was 97% (95%
confidence interval [CI], 95%-98%) for the prediction of malignancy. In 656
patients with ET >=4 mm, REC scoring effectively predicted a high probability of
malignancy with sensitivity (95% confidence interval) of 92% (95% CI, 87%-95%)
and specificity of 94% (95% CI, 91%-96%). An REC score of 0 was present in 206
(32%) patients with ET >=4 mm and was associated with a low negative likelihood
ratio of 0.026 for EC. There were only 7 patients with EC/atypical hyperplasia
among these 206 patients. CONCLUSION: The REC scoring system identified or ruled
out most ECs, clearly showing that more specific image analysis at first-line TVS
can accelerate the diagnosis of EC in patients with PMB and may allow for
improved selection of second-line strategies in patients with ET >=4 mm.
PMID- 29944933
TI - Acrylamide-induced alterations in the cocaine- and amphetamine-regulated peptide
transcript (CART)-like immunoreactivity within the enteric nervous system of the
porcine small intestines.
AB - The main goal of the present study was to determine the influence of low and high
doses of acrylamide on CART-like immunoreactivity within the ENS of the porcine
small intestines. Investigation was performed on 15 sexually immature female
pigs, divided into three groups: control group, where empty gelatin capsules were
administered, and two experimental groups, where capsules containing low or high
doses of acrylamide were given. After 28days of acrylamide exposure all animals
were euthanized with a gradual overdose of anaesthetics. Immediately after
euthanasia fragments of the duodenum, jejunum and ileum were collected and fixed.
Then, 14MUm-thick cryostat sections were processed for routine double-labelling
immunofluorescence using primary antisera directed towards a pan neuronal marker
protein gene-product 9.5 (PGP 9.5) and cocaine- and amphetamine-regulated
peptide transcript (CART). During the present investigation, CART-LI cell bodies
were detected in all types of enteric plexuses of duodenum, jejunum and ileum.
Acrylamide intoxication resulted in a significant increase in expression of CART
in the intramural neurons of the porcine small intestines, especially in
myenteric plexuses. It may suggest participation of CART in neuronal protection
and recovery processes within the gut. Moreover, results of the present study
suggest that even low doses of acrylamide cause a significant response of ENS
neurons.
PMID- 29944934
TI - Antifungal photodynamic inactivation against dermatophyte Trichophyton rubrum
using nanoparticle-based hybrid photosensitizers.
AB - Trichophyton rubrum is one of the most common dermatophytes, which can cause
fungal nail and ringworm infections. Infections associated with T. rubrum have
become a global phenomenon. Herein, we report the antifungal photodynamic
inactivation of T. rubrum (ATCC 28188) using the mesoporous silica-coated silver
nanoparticle-based hybrid photosensitizers without involving antifungal drugs.
Results show that the hybrid photosensitizers display low cytotoxicity under the
experimental conditions where significant killing (~3 orders of magnitude)
against T. rubrum is observed. These results demonstrate the potential
applications of the nanoparticle-based hybrid photosensitizers in antifungal
photodynamic therapy against T. rubrum.
PMID- 29944936
TI - Pirin: A novel redox-sensitive modulator of primary and secondary metabolism in
Streptomyces.
AB - Pirins are evolutionarily conserved iron-containing proteins that are found in
all kingdoms of life, and have been implicated in diverse molecular processes,
mostly associated with cellular stress. In the present study, we started from the
evidence that the insertional inactivation of pirin-like gene SAM23877_RS18305
(pirA) by PhiC31 Att/Int system-based vectors in spiramycin-producing strain
Streptomyces ambofaciens ATCC 23877 resulted in marked effects on central carbon
and energy metabolism gene expression, high sensitivity to oxidative injury and
repression of polyketide antibiotic production. By using integrated
transcriptomic, proteomic and metabolite profiling, together with genetic
complementation, we here show that most of these effects could be traced to the
inability of the pirA-defective strain to modulate beta-oxidation pathway,
leading to an unbalanced supply of precursor monomers for polyketide
biosynthesis. Indeed, in silico protein-protein interaction modeling and in vitro
experimental validation allowed us to demonstrate that PirA is a novel redox
sensitive negative modulator of very long-chain acyl-CoA dehydrogenase, which
catalyzes the first committed step of the beta-oxidation pathway.
PMID- 29944937
TI - Kinetic, spectroscopic and computational docking study of the inhibitory effect
of the pesticides 2,4,5-T, 2,4-D and glyphosate on the diphenolase activity of
mushroom tyrosinase.
AB - The inhibitory effect of 2,4,5-T, 2,4-D, glyphosate and paraquat on the
diphenolase activity of mushroom tyrosinase for oxidation of L-DOPA has been
investigated by kinetic measurements, fluorescence spectroscopy and computational
docking analysis. 2,4,5-T and 2,4-D inhibit the diphenolase activity of the
enzyme following a competitive mechanism, while glyphosate is a mixed inhibitor
according to Lineweaver-Burk kinetic analysis. The inhibitory activity follows
the order glyphosate >2,4,5-T > 2,4-D with IC50 values of 65, 90 and 106 MUM,
respectively. Intrinsic tyrosinase fluorescence quenching and computational
docking analysis suggest that 2,4,5-T and 2,4-D interact with the active site of
the enzyme through hydrophobic interactions, while glyphosate also interacts with
external residues of the active site of the enzyme by hydrogen bonding and
hydrophilic interactions inducing conformational changes in the protein
structure.
PMID- 29944935
TI - Nitro-fatty acids: New drug candidates for chronic inflammatory and fibrotic
diseases.
AB - Nitrated oleic acid (NO2-OA) was first identified in 2003, and after the
characterization of its formation and thiol reactivity, it was used as a
prototypical molecule to investigate the physiological actions of endogenous
nitrated fatty acids (NO2-FA). Based on in vitro observations showing significant
activation of cytoprotective and anti-inflammatory signaling responses by NO2-FA,
experiments were designed to determine their pharmacological potential. Supported
by strong intellectual protection and favorable pharmacokinetic and
pharmacodynamic data, 10-NO2-OA (CXA-10) underwent pharmaceutical development as
a drug to treat fibrotic and inflammatory diseases. NO2-FA are at the
intersection of three unconventional drug candidate classes that include 1) fatty
acids, 2) metabolic intermediates and 3) electrophilic molecules. These three
groups use different scaffolds for drug development, are characterized by broad
activities and are individually gaining traction as alternatives to mono-target
drug therapies. In particular, NO2-FA share key characteristics with currently
approved pharmacological agents regarding reactivity, distribution, and mechanism
of action. This review first presents the characteristics, liabilities, and
opportunities that these different drug candidate classes display, and then
discusses these issues in the context of current progress in the preclinical and
clinical development of NO2-FA as drugs. Lessons learned from the novel
approaches presented herein were considered early on during development to
structurally define and improve NO2-FA and their disease targets.
PMID- 29944939
TI - Effectively preparing soluble ovomucin with high antiviral activity from egg
white.
AB - Ovomucin has a great potential because of its numerous bioactivities, which makes
it an attractive molecule for industrials. However, to isolate soluble ovomucin
without degradation and contamination remains a challenge. In this study,
ovomucin of high purity (99.13%) was obtained in good yield (3.02 g kg-1 fresh
egg white) via an improved two-step precipitation followed by gel filtration
chromatography. The IC50 of the preparation for three representative new disease
virus strains named LaSota, Mukteswar and V-4 is 1.99, 4.95 and 5.78 * 10-3 g L
1, respectively. Produced ovomucin showed limited reduction in the
hemagglutination inhibition activity against all of the virus strains during the
purification. Infrared spectroscopy of the ovomucin preparation indicated
extensive glycosylation and sulfation. Amino acid analysis found that it was rich
in alanine, glutamic acid, threonine and valine residues, which is typical in
mucins. The improved process developed in this study is an alternative approach
to obtain pure ovomucin with elevated antiviral activity and purity, which may
significantly push forward the further research on bioactivities of ovomucin.
PMID- 29944938
TI - Development and characterization of agar-based edible films reinforced with nano
bacterial cellulose.
AB - Nano-bacterial cellulose (BC), as a reinforcing agent, was used to prepare the
agar-based edible films. Effects of BC content (0, 3, 5, 8 and 10%, wt% based on
the agar) on the rheological properties of film-forming solution (FFS), and on
structure, morphology, crystallinity, and thermal properties of films were
investigated. Results of rheological and FTIR analyses revealed that interactions
between BC and agar were formed through hydrogen bonds. The crystallinity and the
thermal stability of films were improved by addition of BC analyzed by XRD and
TGA, respectively. Compared with high BC concentrations (8-10%), a good
dispersion of BC at low concentrations (3-5%) in the films was observed by SEM.
Moreover, BC addition (10%) significantly decreased moisture content (MC), water
solubility (WS) and water vapor permeability (WVP) by 60.4%, 13.3% and 25.7%,
respectively. The tensile strength (TS) of films increased from 22.10 to 44.51
MPa after addition of BC (0-10%), whereas the elongation at break (EAB) initially
increased with increasing BC concentrations (0-5%), and then decreased with
further addition of BC (8-10%). Consequently, agar-based edible films reinforced
by moderate nano-BC have the potential as a packaging film for food products.
PMID- 29944940
TI - Biochemical and functional characterization of an atypical plant l-arginase from
Cilantro (Coriandrum sativam L.).
AB - Arginase is one of the key enzymes responsible for maintaining the essential
levels of nitrogen among plants, but biochemical and functional characterization
of arginase among plants is limited. While screening for stable plant arginase,
we found cilantro possessing an abundant and stable arginase. We purified
arginase to apparent homogeneity (3300-fold purification) with a specific
activity of 81,728 nmoles of urea formed/mg of protein/min and its eight-tryptic
fragments had amino acid sequences identical to Arabidopsis thaliana arginase.
Cilantro arginase exhibited absolute requirement for Mn2+ (0.5 mM-1 mM). Unlike
other known plant arginases, cilantro arginase did not hydrolyse d-arginine and
other arginine analogues. While for sulfhydryl reagents the enzyme was sensitive,
l-NOHA, an arginase inhibitor showed only moderate inhibition - a property
distinct from tomato arginase. We also found arginine derived amino acids and
polyamines can regulate cilantro arginase in vitro. In addition, we also noticed
an increase in cilantro arginase activity to both biotic and abiotic stress. We
conclude that, cilantro may be used as a model plant to study plant arginases and
to delineate arginase role, beyond its classical role in nitrogen recycling and
polyamine biosynthesis.
PMID- 29944941
TI - Production and characterization of CMC-based antioxidant and antimicrobial films
enriched with chickpea hull polysaccharides.
AB - In the present study, polysaccharides from chickpea hull (CHPS) were incorporated
into carboxymethyl cellulose (CMC) for the development of CMC-based films. The
physical and mechanical properties, color, transmittance, antioxidant and
antimicrobial activities were investigated, and differential scanning calorimetry
(DSC), Fourier transform-infrared (FT-IR) spectroscopy and thermogravimetric
analysis (TGA) were applied to study the potential interaction, structure and
thermal stabilization of the prepared films. The results revealed that some
physical and mechanical properties of films, like moisture content, elongation at
break and water vapor permeability, were decreased. While thickness, swelling
ratio, water solubility and tensile strength were significantly increased (p <
0.05) compared with control film. Furthermore, the films exhibited potential
antioxidant effects on DPPH and ABTS free radicals. The results of scanning
electron microscopy showed rough and heterogeneous morphology for CMC-CHPS films
while control film exhibited smooth, homogenous and compact structure. FT-IR
results reflected good interaction of chemical groups and bonds between CMC and
CHPS. DSC results showed that glass transition temperature increased
significantly (p < 0.05) from 82.68 to 90.39 degrees C compared with control of
78.21 degrees C. Thermal stability of all films was improved, indicating that
the films could be used as biocomposite materials for packaging of food products.
PMID- 29944942
TI - Protease-based cross-linked enzyme aggregates with improved catalytic stability,
silver removal, and dehairing potentials.
AB - Proteases have gained special research place due to their broader activity
spectrum and applied perspectives for different industrial sectors. The present
research focused on three aims, i.e., (1) to identify the best protease producer
strain among three different Aspergillus strains, (2) the development of protease
based cross-linked enzyme aggregates (CLEAs) and (3) silver removal and dehairing
potentialities of developed CLEAs. A. flavus gave optimum activity (98.50 U/mL)
with the culture conditions (pH -7.5, 35 degrees C, inoculum 2.5 mL and
fermentation time 48 h) by applying RSM under CCD. The protease-CLEAs were
developed with recovery activity (37.45%) by optimizing conditions through RSM
under CCD (80% ammonium sulfate, 65 mM glutaraldehyde, and 0.15 mM BSA). The
adequacy of the model was checked by ANOVA, and the interactions among different
variables were plotted using 3-D graphs. The characterization profile revealed
high pH and thermal stability at pH -9 and 60 degrees C, respectively. The
kinetic study revealed lower KM and higher Vmax values (31.02 MUM and 91.16 U/mL,
respectively) after CLEAs formation, as compared to the free protease (61.42 MUM
and 84.45 U/mL, respectively). By applying on X-ray film and animal hides,
protease-CLEAs showed the best activity with minimum time as compared to free
protease.
PMID- 29944943
TI - Characterization of bio-based plastic made from a mixture of Momordica charantia
bioactive polysaccharide and choline chloride/glycerol based deep eutectic
solvent.
AB - Momordica charantia bioactive polysaccharide (MCBP) was used as an alternative
source for the production of bio-based plastics (BPs) with choline
chloride/glycerol-based deep eutectic solvent (DES) as a plasticizer. In this
study, MCBP was initially extracted using 0.1 M citric acid at temperature 80
degrees C for 2 h, precipitated using ethanol, and then lyophilized.
Subsequently, seven BPs were prepared: MCBP without plasticizer (MCBP), with 1%
(w/w) of glycerol (MCBP-G), or with 1% (w/w) of DES at different choline
chloride/glycerol molar ratios (i.e. 1.5:1, 1:1, 1:1.5, 1:2, and 1:3). The
properties of these BPs were then investigated. Results showed that the tensile
strains, stresses and moduli were in the range of 1.3-13.3%, 4.8-19.1 MPa and 132
2487 MPa, respectively. The melting temperatures were found in the range of 92.6
111.4 degrees C whereas the moisture absorptions and water vapour transmission
rates (WVTR) of BPs were 1.4-6.5% and 3.6-5.4 mg/m2.s, respectively. The results
also showed that these BPs exhibited bioactivities, such as microbial inhibitory
activity (19.5-32.3 mm), free radical scavenging activity (10.3-18.3%) and ferric
reducing antioxidant power (FRAP, 16.1-20.0 mM). In addition, it was observed
that using DES as a plasticizer had improved the properties of BP, such as
tensile strain (354.7-937.5%), melting temperature (4.6-20.3%), radical
scavenging activity (0.6-88.6%), FRAP (0.9-18.7%) and antimicrobial activity
(12.3-33.6%) compared to MCBP, due to the fact DES has caused different degrees
of plasticization via hydrogen bonds and ionic bonds with the polymer chains, and
induced a lower pH condition. Therefore, it was suggested that these BPs with DES
could contribute to food preservation properties.
PMID- 29944944
TI - The first complete mitochondrial genome of Bactrocera tsuneonis (Miyake)
(Diptera: Tephritidae) by next-generation sequencing and its phylogenetic
implications.
AB - Bactrocera tsuneonis (Miyake), generally known as the Japanese orange fly, is
considered to be a major pest of commercial citrus crops. It has a limited
distribution in China, Japan and Vietnam, but it has the potential to invade
areas outside of Asia. More genetic information of B. tsuneonis should be
obtained in order to develop effective methodologies for rapid and accurate
molecular identification due to the difficulty of distinguishing it from
Bactrocera minax based on morphological features. We report here the whole
mitochondrial genome of B. tsuneonis sequenced by next-generation sequencing.
This mitogenome sequence had a total length of 15,865 bp, a typical circular
molecule comprising 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a
non-coding region (A + T-rich control region). The structure and organization of
the molecule were typical and similar compared with the published homologous
sequences of other fruit flies in Tephritidae. The phylogenetic analyses based on
the mitochondrial genome data presented a close genetic relationship between B.
tsuneonis and B. minax. This is the first report of the complete mitochondrial
genome of B. tsuneonis, and it can be used in further studies of species
diagnosis, evolutionary biology, prevention and control.
PMID- 29944945
TI - Study of aggregation in therapeutic monoclonal antibodies subjected to stress and
long-term stability tests by analyzing size exclusion liquid chromatographic
profiles.
AB - Research into stress and stability is essential during the development of
therapeutic proteins to ensure quality and safety of the final medicine. Greater
knowledge of the effects of stress on aggregation can help avoid undesirable
conformational and colloidal instabilities. With this in mind we investigated
five marketed therapeutic monoclonal antibodies (mAbs) namely bebacizumab (BVZ),
cetuximab (CTX), infliximab (IFX), rituximab (RTX) and tratuzumab (TTZ) in their
innovative medicines. These were submitted to different controlled stresses, to
freeze/thaw cycles and used for long-term stability studies once the vials were
opened. Aggregate formation was tracked by analyzing the mAbs chromatographic
profiles by size-exclusion liquid chromatography coupled with diode array
detection. Results indicated that the tendency to aggregate depends on the
particular stress conditions and on the concentration and nature of the mAb, even
though all share similar IgG1-structure. Fragmentation of the mAb produced by the
stress was probably due to the rupture of cystines between the two heavy chains.
Regarding stability study, BVZ, RTX and TTZ proved to be the most stable when
stored at 4 degrees C and in freeze/thaw cycles with no tendency to form
aggregates. INF tends to form aggregates at 0.5 mg/mL, while in CTX, the most
unstable, degradation was detected.
PMID- 29944946
TI - Combating cellular senescence by sirtuins: Implications for atherosclerosis.
AB - Cellular senescence is the permanent cell cycle arrest induced either by
chronological ageing or extrinsic stimuli. Recent researches have identified
cellular senescence as an important mechanism for atherosclerosis, which is the
essential pathophysiological contributor to cardiovascular diseases (CVDs). The
sirtuins are a family of cellular deacetylases with fundamental abilities to
regulate cellular metabolism and a variety of physiological activities. Previous
studies have revealed the anti-ageing functions of sirtuins as the longevity
associated proteins. These advances indicate the potential beneficial functions
of sirtuins in atherosclerosis by affecting cellular senescence. Herein, we
review the recent findings about sirtuins in regulating atherosclerotic cellular
senescence, and discuss the possibility of activating sirtuins as a therapeutic
strategy for combating atherosclerosis.
PMID- 29944947
TI - CONCURRENT EXPOSURE TO HEAVY METALS AND COGNITION IN SCHOOL-AGE CHILDREN IN CONGO
KINSHASA: A COMPLEX OVERDUE RESEARCH AGENDA.
AB - The impact of concurrent exposure to neurotoxic metals is a significant threat to
brain function, mostly in contexts of multiple exposures as seen in the
developing world. Ninety-five children (46 boys and 49 girls, 6 to 11-year old)
from Congo-Kinshasa were assessed for cognition using the Kaufman Assessment
Battery for Children (2nd edition) and exposure to Cr, Cu, Zn, Co, Mn, As, Cd,
Se, Hg, Fe, and Pb by inductively coupled plasma mass spectrometry (ICPMS) in
serum and urine collections. Concentrations of elements were all above normal
ranges except for Cd, Se and Hg. General linear mixed effects models were used to
predict neurocognitive outcomes with variable selection methods including
backward elimination, elastic net, or subsets identified based on subject matter
expertise. After adjusting for sex, age, and SES, urinary Co > 5 ug/l was
associated with poor simultaneous processing (memory)(p = 0.0237). Higher
excretion but normal concentration of Cd in serum was associated with better
memory (p = 0.03), planning (p = 0.05), and overall performance scores (p <
0.01); thus appeared to be neuroprotective. However, higher excretion of Zn had
negative influence on the overall performance scores (p = 0.02). Predictive
neurotoxicology is a challenging task in contexts of multiple and concurrent
exposures. Urinary Co > 5 ug/l is a risk factor for poor neurodevelopmental
outcomes in such contexts. The impact of heavy metals on cognition is dependent
on concentrations of and interactions between toxic and essential elements.
PMID- 29944948
TI - Median preoptic nucleus excitatory neurotransmitters in the maintenance of
hypertensive state.
AB - The crucial role of the median preoptic nucleus (MnPO) in the maintenance of
hydroelectrolytic balance and autonomic regulation have been highlighted.
Recently, the participation of the MnPO in the control of sympathetic nerve
activity was demonstrated in essential hypertension model. However, peculiarities
on the neurochemical changes underlying the differential role of MnPO during
hypertension remain to be clarified. Therefore, this study aimed to investigate
the main excitatory pathways that modulate MnPO neurons in hypertensive rats.
Spontaneously hypertensive rats (SHR) and rats submitted previously to the
Goldblatt protocol (two kidneys; one clip; 2K1C) were used. Rats of both groups
(250 to 350 g, n = 6) were anesthetized with urethane (1.2 g/kg,i.v.) and
instrumented to record mean arterial pressure (MAP), heart rate (HR) and renal
sympathetic nerve activity (RSNA). Nanoinjection (100 nl) of saline (NaCl, 150
mM), losartan (AT1 receptor antagonist; 10 mM) and kynurenic acid (glutamate
receptor antagonist; 50 mM) into the MnPO were performed. In 2K1C rats,
glutamatergic blockade promoted decreases in MAP and RSNA (-19.1 +/- 0.9 mmHg,
21.6 +/- 2.8%, p < 0.05) when compared to saline (-0.4 +/- 0.6 mmHg, 0.2 +/-
0.7%, p < 0.05). Angiotensinergic inhibition also reduced these parameters (-11.5
+/- 1.2 mmHg, -10.5 +/- 1.0%, p < 0.05) in 2K1C. In SHR, Kynurenic acid
nanoinjections produced hypotension and sympathoinhibition (-21.0 +/- 2.5 mmHg,
24.7 +/- 2.4%, p < 0.05), as well losartan nanoinjections (-9.7 +/- 1.2 mmHg; p <
0.05) and RSNA (-12.0 +/- 2.4%, p < 0.05). These findings support the conclusion
that a tonic excitatory neurotransmission exerted by angiotensin II, and mostly
by glutamate in the MnPO could participate in the modulation of blood pressure
and RSNA independent on whether hypertension is primarily neurogenic or is
secondary to stenosis in renal artery.
PMID- 29944949
TI - Effect of pirfenidone on gastric emptying in a rat model.
AB - INTRODUCTION: Gastrointestinal (GI) adverse events (AEs) are commonly reported in
patients with idiopathic pulmonary fibrosis who are treated with pirfenidone.
Taking pirfenidone with a substantial amount of food or dividing the dose over
the course of a meal has been reported to reduce the frequency of GI AEs in
clinical practice. In humans, the maximum plasma concentration (Cmax) of
pirfenidone was reduced when the drug was taken with food compared with the
fasting state, and the lower Cmax was associated with a reduction in GI AE rates.
In this study, the effects of the divided-dose approach and timing of pirfenidone
administration relative to meal intake on gastric emptying were assessed using a
rat model. The aim of this study was to investigate whether modification of
dosing regimens could minimize pirfenidone's effect on inhibition of gastric
emptying. METHODS: Gastric emptying was assessed in male Sprague-Dawley rats
after administration of a test meal by weighing stomach contents at various time
points up to 120 min after the meal. Pirfenidone was administered via oral gavage
either as a single-bolus dose of 30 mg/kg or as divided doses of 3 * 10 mg/kg at
intervals ranging from 10 to 30 min for a total duration of 30 to 90 min. In
addition, the test meal was given either at 30 min before, coincident with, or 30
min following pirfenidone oral administration. RESULTS: Administration of an oral
30-mg/kg single-bolus dose of pirfenidone with a meal resulted in a statistically
significant decrease in gastric emptying in a rat model. The effect of
pirfenidone on decreasing gastric emptying was lessened when the same total dose
(i.e., 30 mg/kg) was administered as 3 divided doses (i.e., 3 * 10 mg/kg) over
intervals up to 30 min in between each divided dose. Pharmacokinetic simulation
suggested that a divided-dosing regimen would decrease pirfenidone Cmax relative
to single-bolus administration. When the same single-bolus dose of 30 mg/kg was
administered 30 min following a meal rather than coincident with a meal,
pirfenidone's effect on decreasing gastric emptying was reduced to the same
extent as when the dose was divided as 3 * 10 mg/kg over a 90-min period.
CONCLUSIONS: Administration of pirfenidone 30 min after a meal as a single-bolus
dose or a divided dose over a 90-min period blunted pirfenidone's effect on
inhibition of gastric emptying in rats compared with pirfenidone administration
as a single-bolus dose coincident with a meal. Decreased gastric emptying, which
is associated with pirfenidone administration, may be one of the contributing
factors leading to GI tolerability issues associated with pirfenidone use in
humans. Modification of the dosing regimen diminished this impact and may provide
insight into possible mitigation strategies to minimize GI-related toxicities in
the clinic.
PMID- 29944950
TI - Expression and clinical significance of COMPASS family of histone
methyltransferases in clear cell renal cell carcinoma.
AB - The regulation of histone 3 lysine 4 (H3K4) methylation code is indispensable for
the cell as any disturbance in this has been associated with many pathologic
conditions, like cancer. The SET domain-containing lysine methyltransferase 2
(KMT2) family of histone methyltransferases was the first to be identified as
writers of H3K4 methylation. In mammals, seven members of the KMT2 family are
responsible for carrying out the bulk of H3K4 methylation. Recent studies
documented alterations in various histone methylases in human cancer, which were
associated with therapeutic and prognostic potential. Notwithstanding, no report
has documented the role of KMT2 family of histone methyltransferases in clear
cell renal cell carcinoma (ccRCC). Therefore, we examined the expression profile
of all the seven KMT2 family members of histone methyltransferases in ccRCC with
the aim to establish their role as prognostic or therapeutic targets. Real-time
PCR was employed to study the expression of KMT2 family genes using specific
primers in 50 cases of ccRCC. The mRNA levels were correlated with stage, grade,
and metastasis of the tumor. Among seven genes, KMT2G was significantly up
regulated in higher stages of the tumor as compared to low stage tumors (p =
0.017). Similarly, KMT2G levels were higher in the metastatic tumor (p = 0.027).
Additionally, some of the KMT2G target genes were found to be up-regulated in
metastatic tumors as compared to non-metastatic. ROC curve indicated KMT2G as a
good marker for discriminating metastatic tumors from non-metastatic tumors (AUC
= 0.738). Thus, we conclude that KMT2G histone methyltransferase could be a good
prognostic marker for ccRCC. Additionally, KMT2G can also serve as a therapeutic
target for ccRCC.
PMID- 29944951
TI - The chrysanthemum leaf and root transcript profiling in response to salinity
stress.
AB - RNA-Seq was applied to capture the transcriptome of the leaf and root of non
treated and salinity-treated chrysanthemum cv. 'Jinba' plants. A total of 206,868
unigenes of mean length 849 nt and of N50 length 1363 nt was identified; of these
about 64% (> 132,000) could be functionally assigned. Depending on the severity
of the salinity stress, differential transcription was observed for genes
encoding proteins involved in osmotic adjustment, in ion transport, in reactive
oxygen species scavenging and in the regulation of abscisic acid (ABA) signaling.
The root stress response was dominated by the up-regulation of genes involved in
ion transport, while that of the leaf reflected the plant's effort to make
osmotic adjustments and to regulate Ca2+ transport. An array of known
transcription factors (WRKY, AP2/ERF, MYB, bHLH and NAC) were differentially
transcribed.
PMID- 29944952
TI - Emerging role and therapeutic implication of Wnt signaling pathways in liver
fibrosis.
AB - Activation of hepatic stellate cells (HSCs) is a pivotal cellular event in liver
fibrosis. Therefore, improving our understanding of the molecular pathways that
are involved in these processes is essential to generate new therapies for liver
fibrosis. Greater knowledge of the role of the Wnt signaling pathway in liver
fibrosis could improve understanding of the liver fibrosis pathogenesis. The aim
of this review is to describe the present knowledge about the Wnt signaling
pathway, which significantly participates in liver fibrosis and HSC activation,
and look ahead on new perspectives of Wnt signaling pathway research. Moreover,
we will discuss the different interactions with Wnt signaling pathway-regulated
liver fibrosis. The Wnt signaling pathway modulates several important aspects of
function, including cell proliferation, activation and differentiation. Targeting
the Wnt signaling pathway can be a promising direction in liver fibrosis
treatment. We discuss new perspectives of Wnt signaling pathway activation in
liver fibrosis. For example, antagonist to Wnt and Wnt ligands could inhibit
liver fibrosis by regulating Wnt/beta-catenin signaling pathway. These findings
identify the Wnt signaling pathway as a potentially important for therapeutic
targets in liver fibrosis. Future studies are needed in order to find safer and
more effective Wnt-based drugs.
PMID- 29944953
TI - Diverse genetic alterations responsible for post-exposure colistin resistance in
populations of the same strain of Klebsiella pneumoniae.
AB - The intra- and interstrain diversity of genetic alterations in Klebsiella
pneumoniae after exposure to colistin was investigated. Four colistin-susceptible
K. pneumoniae strains with different sequence types were exposed to 2 mg/L
colistin, the average steady-state plasma concentration. After exposure, 10
single-step colistin-resistant mutants were selected in vitro from each K.
pneumoniae strain. Minimum inhibitory concentrations (MICs) were evaluated by
broth microdilution. Nucleotide sequences of genes associated with colistin
resistance (phoPQ, pmrAB, mgrB and crrAB) were determined, and the mRNA
expression levels of pbgP, phoP, phoQ, pmrD, pmrA and pmrB were measured by
quantitative real-time polymerase chain reaction. Colistin MICs for single-step
mutants ranged from 4 to >64 mg/L. Diverse amino acid alterations in pmrB, phoP,
phoQ and mgrB, including insertion sequences, were identified in the colistin
resistant mutants. Different mutations were found even among mutants originating
from the same parental strain, and several mutants displayed no mutations in the
tested genes. While most colistin-resistant mutants showed elevated expression of
pbgP, seven showed no increase compared with their susceptible parental strain,
and some mutants exhibited no overexpression of pmrAB, phoPQ or pbgP. These
results demonstrate the diversity of genetic variations in colistin-resistant
populations derived from the same parental strain, and suggest that there are
still unknown mechanisms of colistin resistance in K. pneumoniae.
PMID- 29944954
TI - Identification of CFE-2, a new plasmid-encoded AmpC beta-lactamase from a
clinical isolate of Citrobacter freundii.
AB - A clinical isolate of Citrobacter freundii (JA99) obtained from a bile culture of
a Taiwanese patient was found to produce a plasmid-encoded beta-lactamase
conferring resistance to oxyimino-cephalosporins and cephamycins. Resistance
arising from production of the beta-lactamase could be transferred by conjugation
with an IncW plasmid (pJA99) into Escherichia coli J53. The substrate and
inhibition profiles of this enzyme resembled that of an AmpC beta-lactamase. The
resistance gene of pJA99, cloned and expressed in E. coli DH5alpha, was shown to
contain an open reading frame showing 92% amino acid identity with the plasmid
encoded enzyme CFE-1 of E. coli KU6400. DNA sequence analysis also identified a
gene upstream of ampC in pJA99 whose sequence was 95.0% identical to the ampR
gene from E. coli KU6400. In addition, orf1, the fumarate operon (frdABCD), blc,
lolB and repB surrounding the ampR-ampC genes in C. freundii were identified.
This DNA fragment was absent in other Citrobacter spp. Therefore, we describe a
new plasmid-encoded AmpC beta-lactamase, named CFE-2. This study highlights the
emergence of broad-spectrum cephalosporin resistance in C. freundii owing to a
new type of AmpC beta-lactamase.
PMID- 29944955
TI - MCR-1-positive colistin-resistant Escherichia coli in immunocompromised
hospitalised patients.
PMID- 29944956
TI - Relationship between mold exposure, specific IgE sensitization, and clinical
asthma: A case-control study.
AB - BACKGROUND: Most of the findings related to the noxious effect of mold
sensitization on asthma come from investigations based on Alternaria alternata,
Cladosporium herbarum, and Aspergillus fumigatus. However, species such as
Penicillium spp, Cladosporium sphaerospermum, Cladosporium cladosporioides, or
Aspergillus versicolor display a more pronounced indoor tropism, and their
potential harmful respiratory effects cannot be neglected. OBJECTIVE: The goal of
this work was to relate mold sensitizations with asthma severity and with the
level of indoor mold contamination among mold-sensitized patients with asthma and
nonsensitized patients with asthma. METHODS: A case-control study was conducted
and several asthma severity markers were compared between patients with asthma
with and without mold sensitization. Indoor contamination of patients' dwellings
was also investigated. RESULTS: Our findings confirmed the association between
sensitization to A fumigatus and severity for patients with asthma in contrast
with sensitization to other species. Indoor mold contamination was detected in
approximately 90% of dwellings. Overall mold exposure was not associated with
asthma severity. However, regardless of the sensitization, exposure to A
fumigatus and Penicillium spp in dust was linked to an increased risk of severe
asthma. CONCLUSION: The harmful nature of mold sensitization and mold exposure
for patients with asthma was not confirmed in this study. However, sensitization
to A fumigatus was associated with an increased risk for severe asthma. A better
investigation of the properties of Penicillium spp is recommended because its
exposure was found to be associated with a more pronounced impairment of lung
function.
PMID- 29944957
TI - Mitigation of the global impact of Lassa fever: Have we investigated enough about
this Arenavirus? - A bibliometric analysis of Lassa Fever research.
PMID- 29944958
TI - Purification and characterization of the antibacterial peptidase lysostaphin from
Staphylococcus simulans: Adverse influence of Zn2+ on bacteriolytic activity.
AB - Lysostaphin, a bacteriolytic toxin from Staphylococcus simulans, is a Zn2+
dependent endopeptidase that cleaves pentaglycine cross-bridges found in
peptidoglycan of certain Staphylococci. Here, we have investigated a critical
influence of Zn2+ ions on lysostaphin-induced bioactivity. Initially, we
succeeded in producing a large amount with high purity of the 28-kDa His-tagged
mature lysostaphin via soluble expression in Escherichia coli and subsequent
purification via immobilized-Ni2+ affinity chromatography (IMAC). The purified
monomeric bacteriocin exhibited concentration-dependent bioactivity against S.
aureus and its methicillin-resistant strain through cell-wall hydrolysis rather
than membrane perturbation. Following pre-incubation of the purified lysostaphin
with exogenous Zn2+, a marked inhibition in staphylolytic activity was observed.
When the pre-mixture was exposed to 1,10-phenanthroline (PNT, a Zn2+-chelator),
the adverse effect of the exogenous Zn2+ on bioactivity was greatly decreased.
Conversely, lysostaphin pre-treated with excess PNT retained relatively high
bioactivity, indicating ineffective chelation of PNT to detach the catalytic Zn2+
from the active-site pocket. Structural analysis of the lysostaphin-catalytic
domain together with amino acid sequence alignments of lysostaphin-like
endopeptidases revealed a potential extraneous Zn2+-binding site found in close
proximity to the Zn2+-coordinating active site. Overall our results provide more
insights into an adverse influence of exogenous Zn2+ ions on staphylolytic
activity of the purified Zn2+-dependent endopeptidase lysostaphin, implicating
the presence of an extraneous inhibitory metal-binding site.
PMID- 29944959
TI - Executive dysfunction in Parkinson's disease: A meta-analysis on the Wisconsin
Card Sorting Test literature.
AB - Executive dysfunctions are a frequently described non-motor symptom in patients
with Parkinsonos disease (PD). However, the nature, extent, variability, and
determinants of executive dysfunctions in PD are still poorly understood. To
improve the characterization of executive dysfunctions in PD, we conducted a meta
analysis of the studies administering the Wisconsin Card Sorting Test (WCST) to
patients with PD and healthy controls. We included k = 161 studies, which allowed
us to precisely estimate the size of PD-related WCST deficits and to run powerful
tests for potential moderators of these deficits. We found robust WCST deficits
in PD, which were medium-to-large in size. These deficits were most pronounced in
patients tested after withdrawal from dopaminergic medication and in samples
characterized by severe motor impairment and long disease duration. Substantial
WCST impairment was also detected in non-demented, non-depressed, and never
medicated patients with PD as well as after conservatively correcting for
publication bias. Based on these findings, impaired WCST performance can be
considered as a major hallmark of executive dysfunction in PD.
PMID- 29944960
TI - Strategies for integrated analysis in imaging genetics studies.
AB - Imaging Genetics (IG) integrates neuroimaging and genomic data from the same
individual, deepening our knowledge of the biological mechanisms behind
neurodevelopmental domains and neurological disorders. Although the literature on
IG has exponentially grown over the past years, the majority of studies have
mainly analyzed associations between candidate brain regions and individual
genetic variants. However, this strategy is not designed to deal with the
complexity of neurobiological mechanisms underlying behavioral and
neurodevelopmental domains. Moreover, larger sample sizes and increased
multidimensionality of this type of data represents a challenge for standardizing
modeling procedures in IG research. This review provides a systematic update of
the methods and strategies currently used in IG studies, and serves as an
analytical framework for researchers working in this field. To complement the
functionalities of the Neuroconductor framework, we also describe existing R
packages that implement these methodologies. In addition, we present an overview
of how these methodological approaches are applied in integrating neuroimaging
and genetic data.
PMID- 29944961
TI - Meta-analytic evidence for a core problem solving network across multiple
representational domains.
AB - Problem solving is a complex skill engaging multi-stepped reasoning processes to
find unknown solutions. The breadth of real-world contexts requiring problem
solving is mirrored by a similarly broad, yet unfocused neuroimaging literature,
and the domain-general or context-specific brain networks associated with problem
solving are not well understood. To more fully characterize those brain networks,
we performed activation likelihood estimation meta-analysis on 280 neuroimaging
problem solving experiments reporting 3166 foci from 1919 individuals across 131
papers. The general map of problem solving revealed broad fronto-cingulo-parietal
convergence, regions similarly identified when considering separate mathematical,
verbal, and visuospatial problem solving domain-specific analyses. Conjunction
analysis revealed a common network supporting problem solving across diverse
contexts, and difference maps distinguished functionally-selective sub-networks
specific to task type. Our results suggest cooperation between representationally
specialized sub-network and whole-brain systems provide a neural basis for
problem solving, with the core network contributing general purpose resources to
perform cognitive operations and manage problem demand. Further characterization
of cross-network dynamics could inform neuroeducational studies on problem
solving skill development.
PMID- 29944962
TI - Interoception is associated with heartbeat-evoked brain potentials (HEPs) in
adolescents.
AB - Heartbeat-evoked brain potentials (HEPs) are an index of the cortical reflection
of cardiac interoceptive signals. Studies which have examined interoception in
adolescents with the use of HEPs are not known to the authors so far. This study
investigated the function of the HEP as a marker of interoception in adolescents.
EEG and ECG were recorded in 46 adolescents during a resting condition and during
a heartbeat detection task. Participants were asked for confidence in their
interoceptive accuracy during heartbeat perception. HEPs appeared during both
conditions, showing maximal activity over frontocentral electrodes in the
heartbeat condition, and highest activity over occipital locations in the resting
condition. Interoceptive accuracy (IAc) was positively associated with the HEP at
frontocentral locations only for the heartbeat condition. Interoceptive
sensibility was not associated with the HEP. No significant association between
IAc and interoceptive sensibility was revealed. Our results highlight the
relevance of the HEP as a neural marker of interoception in adolescents. Its use
as an indicator of vulnerability for affective, physical and mental dysfunctions
during adolescence should be exploited in future studies.
PMID- 29944963
TI - Altered neural inhibition responses to food cues after Roux-en-Y Gastric Bypass.
AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is a highly effective weight
loss intervention that often reduces preference and intake of high-energy foods.
Research into the neural mechanisms behind this shift has mainly focused on
reward processing of food cues. However, the ability to successfully control food
intake and thereby weight-loss also depends on inhibitory control capacity. We
investigated whether RYGB leads to alterations in neural inhibitory control in
response to food cues. METHODS: A food-specific go/no-go task with pictures of
high-energy (desserts) and low-energy foods (vegetables), was used to assess
neural inhibition responses before and after RYGB with functional magnetic
resonance imaging. Data from 18 morbidly obese patients (15 females; age 41 +/-
11 years; BMI 42 +/- 4 kg/m2 before; BMI 36 +/- 4 kg/m2 after) were analysed. Pre
and post-RYGB BOLD fMRI responses were compared for response inhibition towards
high- and low-energy foods. Participants were tested in a satiated state.
RESULTS: Response inhibition to high-energy foods was associated with increased
activation of the right lateral prefrontal cortex (PFC), right medial PFC,
dorsolateral PFC, right middle cingulate cortex and the right inferior frontal
operculum (involved in inhibitory control), after compared to before surgery.
Response inhibition to low-energy foods elicited diminished post- compared to pre
surgery responses in the left superior temporal pole, right parahippocampal gyrus
and right hypothalamus (involved in metabolic control). CONCLUSION: Neural
changes indicate improved response inhibition towards high-energy food cues,
altered influence of metabolic control during response inhibition towards low
energy food cues and a more positive attitude to both high-energy and low-energy
food after RYGB. Alterations in neural circuits involved in inhibitory control,
satiety signalling and reward processing may contribute to effective weight-loss
after RYGB.
PMID- 29944964
TI - Interoceptive accuracy scores from the heartbeat counting task are problematic:
Evidence from simple bivariate correlations.
AB - Interoception, the capacity to perceive internal bodily states, is thought to
influence cognitive, affective and interpersonal functioning. It is frequently
assessed using the heartbeat counting task, introduced recently in interoceptive
research. In this task participants are requested to count their heartbeats
without relying on external cues. Interoceptive Accuracy (i.e., IAcc) scores are
then computed based on absolute comparisons between actual and reported
heartbeats. In a large sample of participants (N = 572), we observed that,
whereas IAcc scores are meant to be theoretically agnostic to error type (i.e.,
over- or underestimation of heartbeats), these scores massively (i.e., > 95%)
reflect under-reports. Of concern too, the correlation between actual and
reported heartbeats is low overall (r = .16), varies non-linearly across IAcc
score quantiles, and suggests undistinguishable interoceptive capacities within
the top 60% IAcc scorers. We also found that IAcc scores, which are conceptually
independent from actual heart rates, are structurally bound to them. Finally, we
show that IAcc scores vary across the time intervals used in the task. We
encourage researchers using this score for studying cognitive and emotional
processes to reconsider its meaning.
PMID- 29944965
TI - CK2 inhibition confers functional protection to young and aging axons against
ischemia by differentially regulating the CDK5 and AKT signaling pathways.
AB - White matter (WM) is injured in most strokes, which contributes to functional
deficits during recovery. Casein kinase 2 (CK2) is a protein kinase that is
expressed in brain, including WM. To assess the impact of CK2 inhibition on axon
recovery following oxygen glucose deprivation (OGD), mouse optic nerves (MONs),
which are pure WM tracts, were subjected to OGD with or without the selective CK2
inhibitor CX-4945. CX-4945 application preserved axon function during OGD and
promoted axon function recovery when applied before or after OGD. This protective
effect of CK2 inhibition correlated with preservation of oligodendrocytes and
conservation of axon structure and axonal mitochondria. To investigate the
pertinent downstream signaling pathways, siRNA targeting the CK2alpha subunit
identified CDK5 and AKT as downstream molecules. Consequently, MK-2206 and
roscovitine, which are selective AKT and CDK5 inhibitors, respectively, protected
young and aging WM function only when applied before OGD. However, a novel pan
AKT allosteric inhibitor, ARQ-092, which targets both the inactive and active
conformations of AKT, conferred protection to young and aging axons when applied
before or after OGD. These results suggest that AKT and CDK5 signaling contribute
to the WM functional protection conferred by CK2 inhibition during ischemia,
while inhibition of activated AKT signaling plays the primary role in post
ischemic protection conferred by CK2 inhibition in WM independent of age. CK2
inhibitors are currently being used in clinical trials for cancer patients;
therefore, our results will provide rationale for repurposing these drugs as
therapeutic options for stroke patients by adding novel targets.
PMID- 29944966
TI - Extrapancreatic glucagon: Present status.
AB - Pancreatic alpha cells are generally considered the only source of glucagon
secretion in humans. In the 1970s several groups investigating totally
pancreatectomised animals reported that glucagon-like immunoreactive material
could be detected in the gastrointestinal tract and reopened the question of an
extrapancreatic source of glucagon proposed in 1948 when a hyperglycaemic
substance was found in the gastrointestinal tract of dogs and rabbits.
Nevertheless, over the years, controversy about the existence of extrapancreatic
glucagon has flourished as it proved difficult to accurately measure fully
processed 29-amino acid glucagon. Recent advances in analytical methods have
increased sensitivity and specificity of glucagon assays and, furthermore,
technical advances in mass spectrometry-based proteomics have made the detection
of low-abundant peptides, such as glucagon, in human plasma more accurate. Here
we review new data on extrapancreatic glucagon secretion in the context of
historical data and recent analytical breakthroughs. Furthermore, the source,
regulation and potential physiological role of extrapancreatic glucagon are
discussed and ongoing challenges and knowledge-gaps are outlined.
PMID- 29944968
TI - 2020 vision - An overview of prospects for diabetes management and prevention in
the next decade.
AB - After a century of medical progress, people nowadays live longer with diabetes
than ever before. However, current preventative approaches, compounded in part by
increased life-expectancy, are failing to reduce the prevalence of diabetes.
Cardiovascular sequelae account for many of the four million deaths annually
attributable to diabetes. Evidence indicates that certain glucose-lowering
medications can improve vascular outcomes in some people with type 2 diabetes,
which, together with better understanding of using multiple therapies
concurrently, offers opportunities for beneficial personalization of medication
regimens. However, further well-designed long-term studies are needed to evaluate
cardiovascular benefits and safety of new and older medications, particularly in
users typical of everyday diabetes care. Although there are numerous other
promising advances in pharmacotherapies and biotechnology, these will probably be
unaffordable for most people with diabetes globally. Therefore, effective
national public health approaches will be essential to reducing the incidence of
diabetes and its associated burdens; these may entail politically controversial
measures to change unhealthy lifestyle behaviours. Stakeholders could learn from
past failures and emulate successes in other health-care initiatives. Without
early action at all levels, we face a future in which approaching one-quarter of
humans will have diabetes, with more than half afflicted during their lifetime.
PMID- 29944967
TI - Cost-related medication non-adherence among U.S. adults with diabetes.
AB - AIMS: To examine factors that affect cost-related medication non-adherence (CRN),
defined as taking medication less than as prescribed because of cost, among
adults with diabetes and to determine their relative contribution in explaining
CRN. METHODS: Behavioral Risk Factor Surveillance System data for 2013-2014 were
used to identify individuals with diabetes and their CRN. We modeled CRN as a
function of financial factors, regimen complexity, and other contextual factors
including diabetes care, lifestyle, and health factors. Dominance analysis was
performed to rank these factors by relative importance. RESULTS: CRN among U.S.
adults with diabetes was 16.5%. Respondents with annual income <$50,000 and
without health insurance were more likely to report CRN, compared to those with
income >=$50,000 and those with insurance, respectively. Insulin users had 1.24
times higher risk of CRN compared to those not on insulin. Contextual factors
that significantly affected CRN included diabetes care factors, lifestyle
factors, and comorbid depression, arthritis, and COPD/asthma. Dominance analysis
showed health insurance was the most important factor for respondents <65 and
depression was the most important factor for respondents >=65. CONCLUSIONS: In
addition to traditional risk factors of CRN, compliance with annual
recommendations for diabetes and healthy lifestyle were associated with lower
CRN. Policies and social supports that address these contextual factors may help
improve CRN.
PMID- 29944969
TI - Cardiovascular outcome studies in type 2 diabetes: Comparison between SGLT2
inhibitors and GLP-1 receptor agonists.
AB - Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) and glucagon-like
peptide-1 receptor agonists (GLP-1RAs) are two pharmacological classes that have
proven their efficacy to reduce major cardiovascular events (MACEs) in patients
with type 2 diabetes mellitus (T2DM) and established cardiovascular disease in
large prospective cardiovascular outcome trials (CVOTs): EMPA-REG OUTCOME
(empagliflozin), CANVAS (canagliflozin), LEADER (liraglutide) and SUSTAIN 6
(semaglutide). Some heterogeneity appears to exist between the various agents
within the two pharmacological classes. Whether these positive results could be
extrapolated to patients without cardiovascular disease is still unknown. The
underlying mechanisms remain a matter of debate but appear to differ between
SGLT2is and GLP-1RAs. One crucial question is which patient's characteristics
should be taken into account to guide the choice between a SGLT2i or a GLP-1RA
according to a personalized approach. Heart failure should encourage the use of a
SGLT2i whereas moderate to severe chronic kidney disease should favour the
prescription of a GLP-1RA. Despite the results of recent CVOTs, numerous patients
who are good candidates for benefiting of these agents do not receive them in
clinical practice. Currently, there is a paradigm shift in T2DM management,
moving from a primary objective of glucose control to a cardiovascular and renal
protection.
PMID- 29944970
TI - NF2 and ATRX gene copy number losses on a case of ovarian ependymoma.
AB - Ovarian ependymomas are rare glial neoplasms that typically occur in females on
their 3rd to 4th decade of life. They are histologically similar to ependymomas
of the central nervous system (CNS) but may have a broader immunophenotype. We
describe a 27year old female who presented to the emergency room with a 3week
history of cough and shortness of breath. Further workup disclosed a left pelvic
mass and extensive intra-abdominal metastases. Pathology revealed sheets of
monomorphic cells within a fibrillary stroma, papillary projections, true
ependymal rosettes, and pseudorosettes consistent with an ependymoma of ovarian
origin. Next Generation Sequencing (NGS) showed ATRX and NF2 copy number losses.
Fluorescence in situ hybridization (FISH) for EWSR1 demonstrated monosomy of 22q
in greater than 90% of cells. These molecular alterations have not been
previously reported in ovarian or extra-CNS ependymomas.
PMID- 29944971
TI - Giant cell tumor of bone: updated molecular pathogenesis and tumor biology.
AB - Giant cell tumor of bone (GCTB)-related clonal aberrations occur in a background
of epigenetic histone modifications (especially the G34W mutation of H3F3A gene)
that induce cytogenetic abnormalities. Clonal aberrations are closely linked to
the aggressiveness of GCTB. The "neoplastic" mononuclear stromal cells in GCTB
express fundamental RANKLs and various chemokines and cytokines associated with
monocyte recruitment and "reactive" multinucleated giant cells
(osteoclastogenesis). The reciprocal and orchestrated actions between mononuclear
stromal cells and multinucleated giant cells help in the understanding of the
molecular pathogenesis and tumor biology of GCTB. In the future, novel targets in
the updated tumor biology and molecular pathogenesis of GCTB should be explored
and scrutinized for the development of systemic therapy.
PMID- 29944972
TI - MED12 is frequently mutated in ovarian and other adnexal leiomyomas.
AB - In the female genital tract, extrauterine leiomyomas such as those that arise in
the ovary and paraovarian/paratubal regions are rare. Currently, little is known
about the background genetic changes in such adnexal leiomyomas. Recent studies
have found that the MED12 mutation is common in uterine leiomyomas, which
suggests that such mutations may play an oncogenic role in smooth muscle
neoplasms in females. Herein, we examined a series of ovarian and other adnexal
leiomyomas in terms of MED12 mutational status to investigate possible MED12
involvement in the pathogenesis of extrauterine smooth muscle tumors. We
evaluated 10 cases of adnexal leiomyomas (5 ovarian, 3 paraovarian, and 2
paratubal) and 49 cases of ovarian sex cord-stromal tumors as controls. We
performed polymerase chain reaction followed by direct sequencing of exon 2 of
MED12, and immunohistochemical staining for smooth muscle actin and desmin. We
identified somatic MED12 mutations in 90% (9/10) of the adnexal leiomyomas. None
of the sex cord-stromal tumors in the control group harbored MED12 mutations.
Diffuse immunoreactivity for both smooth muscle actin and desmin was
characteristic of adnexal leiomyomas only. Thus, we conclude that ovarian
leiomyomas are distinct from sex cord-stromal tumors. MED12 mutations are key
molecular features of ovarian and other adnexal leiomyomas. We speculate that the
pathogenesis of adnexal leiomyoma is similar to that of its uterine counterpart.
PMID- 29944973
TI - Ovarian carcinomas: at least five different diseases with distinct histological
features and molecular genetics.
AB - Based on histopathology and molecular genetics, ovarian carcinomas are divided
into five main types: high-grade serous (70%), endometrioid (10%), clear cell
(10%), mucinous (3%), and low-grade serous (<5%) carcinomas. These tumors, which
account for over 95% of cases, represent distinct diseases with different
prognoses and treatments. TP53 mutations are identified in almost all (96%) high
grade serous carcinomas (HGSCs). Early p53 loss followed by BRCA loss leads to
deficiency in homologous recombination (DHR) repair, which in turn triggers
chromosomal instability and widespread somatic copy number changes. An
undetermined number of cases of HGSCs originate in the tubal fimbria; however, an
origin from the ovarian surface epithelium cannot be totally excluded. Low-grade
serous carcinomas (LGSCs) most likely represent progression of SBTs. BRAF or KRAS
mutations occur in one-third to one-half of cases. Mucinous carcinomas (MCs)
typically show benign-appearing, borderline, non-invasive and invasive components
indicating tumor progression. KRAS mutations occur in 43.6% of cases and
overexpression/amplification of HER2 in 18.8%. Endometrioid and clear cell
carcinomas (EC and CCC) originate from ovarian endometriosis. Compared with their
uterine counterparts, ECs have a similar frequency of beta-catenin abnormalities
but lower rate of microsatellite instability (MI) and PTEN alterations. ARID1A
mutations occur in both ECs (30%) and CCCs (50%) and may be encountered in
adjacent endometriosis. CCCs carry inactivating PTEN mutations and activating
mutations in PIK3CA in 8% and 33% of cases, respectively. This review summarizes
recent advances in the molecular pathology, which have greatly improved our
understanding of the biology of ovarian carcinomas and are also relevant to
patient management.
PMID- 29944974
TI - Plant-inspired gallolamine catalytic surface chemistry for engineering an
efficient nitric oxide generating coating.
AB - : A novel concept of generating therapeutic gas, nitric oxide (NO) via catalytic
phenolic-amine "gallolamine" surface chemistry is developed. The concept is
realized using plant polyphenol, gallic acid, and a glutathione peroxidase-like
organoselenium compound cystamine or selenocystamine through one-step phenol
amine molecular assembling process. The resulting NO-generating coating with
phenolic-cystamine or -selenocystamine framework showed the ability for long
term, steady and controllable range of NO release rates being unparalleled with
any existing NO-releasing or NO-generating surface engineering toolkits.
STATEMENT OF SIGNIFICANCE: Developing a facile and versatile strategy for a NO
generating coating with long-term, stable and adjustable NO release is of great
interest for the application of blood-contacting materials and devices. Covalent
immobilization of glutathione peroxidase (GPx)-like compound to generate NO from
a material surface by exposure of endogenously existed S-nitrothiol (RSNO) is a
popular strategy. However, it is generally involved in multi-step and complicated
processes. Moreover, the amount of immobilized GPx-like compounds is limited by
the density of introduced reactive functional groups on a surface. Herein, we
propose a novel concept of catalytic plant-inspired gallolamine surface chemistry
for material-independent NO-generating coatings. The concept is realized using
plant polyphenol, gallic acid, and a GPx-like organoselenium compound cystamine
or selenocystamine through one-step phenol-amine molecular assembling process.
Without tedious multi-step synthesis, complicated surface treatments, and leakage
of toxic chemicals, our unprecedentedly simple, histocompatible and biocompatible
phenolic-cystamine or -selenocystamine framework demonstrated long-term, on
demand and facile dose controls of NO generated from the engineering surfaces.
These unique features of such a NO-generating coating imparted a material with
ability to impressively improve anti-thrombogenicity in vivo. This work
constitutes the first report of an interfacial catalytic coating based on
material-independent surface chemistry by plant polyphenols. This concept not
only expands the application of material-independent surface chemistry in an
interfacial catalytic area, but also can be a new platform for antithrombotic
materials.
PMID- 29944976
TI - Changes in amygdala, cerebellum, and nucleus accumbens volumes in bipolar
patients treated with lamotrigine.
AB - The neural mechanisms underlying the therapeutic effects of lamotrigine in
bipolar depression are still unexplored. This preliminary study compares the
effects of a 12-week treatment with lamotrigine on brain volumes in adults with
bipolar disorder (BD).12 BD type II patients (age: 49.33 +/- 9.95 years, 3 males,
9 females) and 12 age and gender-matched healthy controls (HC) (HC; age: 41 +/-
8.60 years, 3 males, 9 females). BD patients were initially administered 25
mg/day of lamotrigine, which was progressively escalated to 200 mg/d. BD
participants underwent brain imaging prior to and following lamotrigine
treatment. A 50% reduction in depressive scores indicated "remission". Bayesian
general linear models controlled for age, gender and intracranial volume were
used to examine changes in relevant brain region following treatment. A posterior
probability > 0.90 indicated evidence that there was an effect of diagnosis or
remission on brain volumes. Probability distributions of interaction effects
between remission and time indicated that BD responders displayed decreased
amygdala, cerebellum and nucleus accumbens volumes following lamotrigine
treatment. No serious adverse side effects were reported. The antidepressant
effects of lamotrigine may be linked to volumetric changes in brain regions
involved in mood and emotional regulation. These findings are preliminary and
replication in a larger sample is warranted.
PMID- 29944975
TI - Incorporating beta-cyclodextrin into collagen scaffolds to sequester growth
factors and modulate mesenchymal stem cell activity.
AB - : The development of biomaterials for a range of tissue engineering applications
increasingly requires control over the bioavailability of biomolecular cues such
as growth factors in order to promote desired cell responses. While efforts have
predominantly concentrated on covalently-bound or freely-diffusible incorporation
of biomolecules in porous, three-dimensional biomaterials, opportunities exist to
exploit transient interactions to concentrate growth factor activity over desired
time frames. Here, we report the incorporation of beta-cyclodextrin into a model
collagen-GAG scaffold as a means to exploit the passive sequestration and release
of growth factors via guest-host interactions to control mesenchymal stem cell
differentiation. Collagen-GAG scaffolds that incorporate beta-cyclodextrin show
improved sequestration as well as extended retention and release of TGF-beta1. We
further show extended retention and release of TGF-beta1 and BMP-2 from beta
cyclodextrin modified scaffolds was sufficient to influence the metabolic
activity and proliferation of mesenchymal stem cells as well as differential
activation of Smad 2/3 and Smad 1/5/8 pathways associated with differential osteo
chondral differentiation. Further, gene expression analysis showed TGF-beta1
release from beta-cyclodextrin CG scaffolds promoted early chondrogenic-specific
differentiation. Ultimately, this work establishes a novel method for the
incorporation and display of growth factors within CG scaffolds via
supramolecular interactions. Such a design framework offers opportunities to
selectively alter the bioavailability of multiple biomolecules within a three
dimensional collagen-GAG scaffold to enhance cell activity for a range of
musculoskeletal regenerative medicine applications. STATEMENT OF SIGNIFICANCE: We
describe the incorporation of beta-cyclodextrin into a model CG-scaffold under
development for musculoskeletal tissue engineering applications. We show beta
cyclodextrin modified scaffolds promote the sequestration of soluble TGF-beta1
and BMP-2 via guest-host interactions, leading to extended retention and release.
Further, beta-cyclodextrin modified CG scaffolds promote TGF-beta1 or BMP-2
specific Smad signaling pathway activation associated with divergent osseous
versus chondrogenic differentiation pathways in mesenchymal stem cells.
PMID- 29944977
TI - Feasibility of anaerobic digestion for contaminated rice straw inoculated with
waste activated sludge.
AB - Anaerobic digestion of the heavy metal-contaminated rice straw inoculated with
waste activated sludge was carried out through an orthogonal array. The results
indicated that the digestion process was optimized with an inoculum to substrate
ratio (I/S) of 0.25, a total solid (TS) content of 5%, and an initial pH of 7.0,
with corresponding total biogas and methane yields of 745.4 and 285.2 mL/g VS,
respectively. Under the optimized conditions, the bioleaching percentages of Cd
and As in the biomass were 13.13% and 42.90%, respectively. According to range
analysis, the biogas yield, methane yield, and bioleaching percentages of Cd and
As in the biomass significantly decreased with an increase in TS content from 5%
to 15%. The results suggested that anaerobic digestion with waste activated
sludge was feasible for achieving both biogas production and bioleaching of heavy
metals from contaminated rice straw.
PMID- 29944978
TI - Clinical development of HER3-targeting monoclonal antibodies: Perils and
progress.
AB - The human epidermal growth factor receptor (HER) family consists of four
transmembrane receptor tyrosine kinases: epidermal growth factor receptor (EGFR),
HER2, HER3, and HER4. They are part of a complex signalling network and stimulate
intracellular pathways regulating cell growth and differentiation. So far,
monoclonal antibodies (mAbs) and small molecule tyrosine kinase inhibitors
targeting EGFR and HER2 have been developed and approved. Recently, focus has
turned to HER3 as it may play an important role in resistance to EGFR- and HER2
targeting therapies. HER3-targeting agents have been undergoing clinical
evaluation for the last 10 years and currently thirteen mAbs are in phase 1 or 2
clinical studies. Single agent activity has proven to be limited, however, the
tolerability was favourable. Thus, combinations of HER3-binding mAbs with other
HER-targeting therapies or chemotherapies have been pursued in various solid
tumor entities. Data indicate that the HER3-binding ligand heregulin may serve as
a response prediction marker for HER3-targeting therapy. Within this review the
current status of clinical development of HER3-targeting compounds is described.
PMID- 29944979
TI - Deconstructing the Gratton effect: Targeting dissociable trial sequence effects
in children, pre-adolescents, and adults.
AB - The Gratton effect refers to the observation that performance on congruency tasks
is often enhanced when the congruency of the current trial matches that of the
previous trial. This effect has been at the center of recent debates in the
literature on cognitive control as researchers have sought to identify the
cognitive and neural underpinnings of the effect. Here, we use a technique known
as reach tracking to demonstrate that the Gratton effect originally observed in
the flanker task is not a singular effect but the result of two separate trial
sequence effects that impact dissociable processes underlying cognitive control.
Further, our results indicate that these dissociable processes follow divergent
developmental trajectories across childhood, pre-adolescence, and adulthood.
Taken together, these findings suggest that manual dynamics can be used to
disentangle how key processes underlying cognitive control contribute to the
response time effects observed across a wide range of cognitive tasks and age
groups.
PMID- 29944980
TI - Changes in cell morphology guide identification of tubulin as the off-target for
protein kinase inhibitors.
AB - In the field of kinase inhibitors for applications in cancer research, tubulin is
emerging as a targeted cellular protein that can significantly contribute to
their activities. However, investigation of kinase inhibitors beyond the kinome
is an area often neglected. Herein, we describe the results of pharmacological
studies using drugs targeting kinases, tubulin or both. A key finding is that if
cells are treated with a kinase inhibitor unintentionally targeting tubulin,
their characteristic shape will diminish within a short timeframe. These changes
in cell morphology are not seen when cells are treated with bona fide kinase
inhibitors that do not directly target tubulin. Thus, early changes in cell
morphology upon treatments are a strong indication that the inhibitor is directly
targeting tubulin. Recognizing tubulin as a target of kinase inhibitors will
build confidence in the future mechanistic studies using kinase inhibitors.
PMID- 29944981
TI - Lipid based nanocarriers: a translational perspective.
AB - Over the recent couple of decades, pharmaceutical field has embarked most
phenomenal noteworthy achievements in the field of medications as well as drug
delivery. The rise of Nanotechnology in this field has reformed the existing drug
delivery for targeting, diagnostic, remedial applications and patient monitoring.
The convincing usage of nanotechnology in the conveyance of medications that
prompts an extension of novel lipid-based nanocarriers and non-liposomal systems
has been discussed. Present review deals with the late advances and updates in
lipidic nanocarriers, their formulation strategies, challenging aspects,
stability profile, clinical applications alongside commercially available
products and products under clinical trials. This exploration may give a complete
idea viewing the lipid based nanocarriers as a promising choice for the
formulation of pharmaceutical products, the challenges looked by the
translational process of lipid-based nanocarriers and the combating methodologies
to guarantee the headway of these nanocarriers from bench to bedside.
PMID- 29944982
TI - Circulating microRNAs as novel biomarkers in heart failure.
PMID- 29944983
TI - Novel balloon-assisted catheter ''unknotting'' technique.
PMID- 29944984
TI - Economic burden of elderly patients with acute myeloid leukemia treated in
routine clinical care in the United States.
AB - This retrospective claims database study examined healthcare utilization (HCU)
and costs associated with acute myeloid leukemia (AML) in 237 elderly patients
who received chemotherapy or a stem cell transplant (SCT) following AML
diagnosis. Patients with secondary AML were excluded. Over the entire follow-up
period, 92.0% of patients had >=1 inpatient admission; 85.7% had >=1 AML-related
admission, and 42.6% had >=1 non-AML-related admission. During inpatient
admissions, 39.2% of patients had >=1 intensive care unit (ICU) admission, with
20.7% having >=1 AML-related ICU admission, and 27.8% having >=1 non-AML-related
ICU admission. Total mean per-patient per-month (PPPM) costs over the follow-up
period were $25,243 (SD: $21,909), with costs from Year 1 ($27,756 [SD: $22,121])
more than double those in Year 2 ($12,953 [SD: $26,334]) following AML diagnosis.
The majority of total costs were medical ($24,512 PPPM [SD: $21,704]), which
included inpatient admissions ($6548 PPPM [SD: $10,777]), other outpatient visits
($5021 PPPM [SD: $7997]), supportive care ($3640 PPPM [SD: $5589], and
chemotherapy administration ($2029 PPPM [SD: $2345]). Healthcare costs of treated
elderly AML patients are substantial, particularly in the first year following
diagnosis. Further research is needed to understand factors contributing to high
costs in various settings of care for elderly AML patients.
PMID- 29944985
TI - Different mode of arrestin-3 binding at the human Y1 and Y2 receptor.
AB - GPCR internalization, which is induced by arrestin recruitment, is an important
mechanism for the regulation of signaling and receptor quantity at the cell
surface. In this study, differences in the mechanism of arrestin-3 (arr-3)
recruitment to the neuropeptide Y1 and Y2 receptor were identified. These
receptors play an essential role in the regulation of feeding, energy homeostasis
and cancer. The Y1R displays high affinity to arr-3, which induces rapid
internalization of the arrestin/receptor complex. In contrast, the Y2R has a
lower affinity for arr-3. Internalization is induced by arrestin binding, but arr
3 is released from the receptor and remains at the membrane while the receptor
internalizes. Moreover, the deletion of the finger loop region of arr-3 reduces
its agonist-dependent recruitment to the Y2R significantly, but not to the Y1R
suggesting different binding conformations. For the first time, the formation of
a supercomplex consisting of Y receptor, Galpha0 protein and arrestin was studied
by BRET-assay. We demonstrated that the Y1R is able to bind Galpha0 protein as
well as arr-3 simultaneously and internalizes as a supercomplex. For the Y2R no
supercomplex formation was observed. By substituting the C-terminus or specific
residues within the intracellular loop 1 and 2 of the receptors, the arr-3
recruitment of the Y1R and Y2R can be switched. Thus, we shed light on the
specific spatio-temporal distribution of Galpha0 protein and arrestin in response
to Y1 versus Y2 receptor activation and identified the molecular determinants.
PMID- 29944986
TI - LSECs express functional NOD1 receptors: A role for NOD1 in LSEC maturation
induced T cell immunity in vitro.
AB - Liver sinusoidal endothelial cells (LSECs) are organ resident APCs capable of
antigen presentation and subsequent tolerization of T cells under physiological
conditions. In this study, we investigated whether LSEC pretreatment with NOD
like receptor (NLR) agonists can switch the cells from a tolerogenic to an
immunogenic state and promote the development of T cell immunity. LSECs
constitutively express NOD1, NOD2 and RIPK2. Stimulation of LSECs with DAP
induced the activation of NF-kappaB and MAP kinases and upregulated the
expression of chemokines (CXCL2/9, CCL2/7/8) and cytokines (IFN-gamma, TNF-alpha
and IL-2). Pretreatment of LSECs with DAP induced significantly increased IFN
gamma and IL-2-production by HBV-stimulated CD8+ T cells primed by DAP-treated
LSECs. Consistently, a significant reduction in the HBV DNA and HBsAg level
occurred in mice receiving T cells primed by DAP-treated LSECs. MDP stimulation
had no impact on LSECs or HBV-stimulated CD8+ T cells primed with MDP-treated
LSECs except for the upregulation of PD-L1. DAP stimulation in vitro could
promote LSEC maturation and activate HBV-specific T cell responses. These results
are of particular relevance for the regulation of the local innate immune
response against HBV infections.
PMID- 29944987
TI - Air pollution health research priorities for India: Perspectives of the Indo-U.S.
Communities of Researchers.
PMID- 29944988
TI - Urinary levels of pyrethroid pesticides and determinants in pregnant French women
from the Elfe cohort.
AB - Pyrethroids are insecticides which are widely used for agricultural and domestic
purposes. The general population can be exposed to them. Given the suspected
effects of pesticides on the development of the foetus, exposure to pyrethroids
during pregnancy is a major public health concern. The objective of this paper is
to describe the urinary levels of the following five pyrethroid metabolites and
their associated determinants among pregnant French women in 2011 enrolled in the
Elfe cohort (n = 1077): a) 3-phenoxy benzoic (3-PBA), b) 4-fluoro-3-phenoxy
benzoic acid (4-F-3-PBA), c) Cis-3-(2,2dibromovinyl)-2,2-dimethyl cyclopropane
carboxylic acid (Cis-DBCA); d) Cis-3-(2,2dichlorovinyl)-2,2-dimethyl cyclopropane
carboxylic acid (Cis-DCCA) and e) Trans-3-(2,2dichlorovinyl)-2,2-dimethyl
cyclopropane-carboxylic acid (Trans-DCCA). The distribution levels were estimated
for each pyrethroid metabolite. Multivariable analyses helped determine the
predictors of these levels. All metabolites except 4-F-3-PBA were detected in all
the urine samples. The mean urinary concentration of the sum of the metabolites
(3-PBA, Cis-DBCA, Cis-DCCA, Trans-DCCA) was 1.18 MUg/L, with the highest
concentrations observed for 3-PBA. A comparison of these levels with other
studies showed that pregnant French women tend to be more exposed to pyrethroids
than their American counterparts, less exposed than Chinese and Caribbean
mothers, and have similar exposure to Japanese mothers. In our study, urinary
levels of pyrethroid metabolites were positively related to smoking during
pregnancy, consuming fish and alcohol, domestic pesticide use and living in the
vicinity of crops during pregnancy. These findings highlight the importance of
non-dietary pathways when evaluating exposure to pyrethroids.
PMID- 29944990
TI - Transitions in the use of multiple substances from adolescence to young
adulthood.
AB - BACKGROUND: Research indicates that many adolescents frequently use multiple
substances. This study examines stability and transitions in the use and co-use
of multiple substances (cigarette, alcohol, marijuana, illicit drugs) from
adolescence to young adulthood. METHODS: Data were collected biennially from 662
youth in six assessments across ten years (2003-2013). We used latent class
analysis (LCA) to classify youth by substances used at each wave and used latent
transition analysis (LTA) to examine transition probabilities across waves.
RESULTS: At each wave, a three-class model best fit the data. Classes included a
poly-use class, that had the highest probabilities of use among all substances, a
co-use class, that had high probabilities of use of alcohol and marijuana, and an
alcohol-dominate class that started with low probabilities of use among all
substances but showed increasing probabilities of alcohol use, at later ages. LTA
showed that the probability of remaining in the poly-use class was the most
stable from one wave to the next, followed by the alcohol-dominate class, and the
co-use class. The most transitions occurred for the co-use class, with more
individuals transitioning to the poly-use class than to the alcohol-dominate
class. CONCLUSIONS: Strong stability among adolescent substance use classes was
found between waves. Transitions were typically to classes using more substances,
although, transitions to use fewer substances was evident for some individuals.
Distinguishing stable and transitioning classes of substance use and co-use
provides opportunities for prevention and intervention to disrupt high-risk use
classes.
PMID- 29944991
TI - Childhood sexual abuse and current suicidal ideation among adolescents: Problem
focused and emotion-focused coping skills.
AB - INTRODUCTION: The present study aims to investigate whether problem-focused and
emotion-focused coping skills were associated with suicidal ideation. In
addition, we examined whether childhood maltreatment (i.e. physical,
psychological, sexual abuse, and neglect) is a risk factor for later-on suicidal
ideation. METHODS: Youths aged 16 or 18 (n = 307, 56% females) from San Diego and
Seattle at Wave 6 and Wave 7 of the LONGSCAN were included in the study. We used
hierarchical logistic regression. RESULTS & CONCLUSIONS: 17.6% reported suicidal
ideation. Those who reported better emotion-focused coping were .80 times less
likely to report suicidal ideation. However, even after controlling for coping
skills, adolescents with sexually abuse histories were 3.08 times more likely to
report suicidal ideation. Our findings suggest implications for early
intervention efforts. Building youth assets through promotion of positive youth
development may serve as a driving force to reduce negative outcomes in youth who
have experienced sexual abuse.
PMID- 29944989
TI - Disparities in substance use behaviors and disorders among adult sexual
minorities by age, gender, and sexual identity.
AB - BACKGROUND: Sexual minorities (SMs) experience elevated rates of substance use
behaviors and disorders relative to heterosexuals; minority stress is theorized
to contribute to these disparities. As SMs are not a homogenous group, analyses
that aggregate SMs across sexual identity, age, or gender obscure important
variation among this population. To date, age- and gender-specific disparities
have not been rigorously examined using a large national sample. METHODS: Using
data on 67,354 adults (ages 18-49) from the 2015 and 2016 National Survey of Drug
Use and Health we examined age- and gender-specific disparities in smoking, heavy
episodic drinking, marijuana use, illicit drug use, and alcohol/substance use
disorder. Age groups were ages 18-25, 26-34, and 35-49. Using logistic
regression, we estimated age- and gender-specific odds ratios for gay/lesbian and
bisexual individuals, relative to heterosexuals; analyses adjusted for
demographic characteristics. RESULTS: Bisexual women had significantly elevated
odds of all outcomes at all ages, relative to heterosexual women. Gay/lesbian
individuals had significantly elevated odds for nearly all outcomes compared to
same-gender heterosexuals at ages 18-25, but not consistently at older ages. For
bisexual men, significant disparities compared to heterosexual men were only
observed at ages 35-49 for marijuana use and alcohol/substance use disorder.
CONCLUSIONS: We found notable within-group differences regarding SM disparities.
While disparities were most pronounced in young adulthood for gay/lesbian
individuals and mid-adulthood for bisexual men, bisexual women uniquely
experienced disparities across all ages. Minority stress experiences may vary
with respect to gender, age/cohort, and sexual identity, resulting in
differential risk for substance use.
PMID- 29944992
TI - Generation of the Rubinstein-Taybi syndrome type 2 patient-derived induced
pluripotent stem cell line (IAIi001-A) carrying the EP300 exon 23 stop mutation
c.3829A > T, p.(Lys1277*).
AB - Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder characterized
by growth retardation, skeletal anomalies and intellectual disability, caused by
heterozygous mutation in either the CREBBP (RSTS1) or EP300 (RSTS2) genes. We
generated an induced pluripotent stem cell line from an RSTS2 patient's blood
mononuclear cells by Sendai virus non integrative reprogramming method. The iPSC
line (IAIi001RSTS2-65-A) displayed iPSC morphology, expressed pluripotency
markers, possessed trilineage differentiation potential and was stable by
karyotyping. Mutation and western blot analyses demonstrated in IAIi001RSTS2-65-A
the patient's specific non sense mutation in exon 23 c.3829A > T, p.(Lys 1277*)
and showed reduced quantity of wild type p300 protein.
PMID- 29944993
TI - Phasic alertness cues modulate visual processing speed in healthy aging.
AB - Warning signals temporarily increase the rate of visual information in younger
participants and thus optimize perception in critical situations. It is unclear
whether such important preparatory processes are preserved in healthy aging. We
parametrically assessed the effects of auditory alertness cues on visual
processing speed and their time course using a whole report paradigm based on the
computational Theory of Visual Attention. We replicated prior findings of
significant alerting benefits in younger adults. In conditions with short cue
target onset asynchronies, this effect was baseline-dependent. As younger
participants with high baseline speed did not show a profit, an inverted U-shaped
function of phasic alerting and visual processing speed was implied. Older adults
also showed a significant cue-induced benefit. Bayesian analyses indicated that
the cueing benefit on visual processing speed was comparably strong across age
groups. Our results indicate that in aging individuals, comparable to younger
ones, perception is active and increased expectancy of the appearance of a
relevant stimulus can increase the rate of visual information uptake.
PMID- 29944994
TI - Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral
insulin resistance.
AB - The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc
transferase [OGT]) that catalyzes the transfer of beta-N-acetylglucosamine
(GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or
threonine residues of nucleocytoplasmic proteins. This process is a common
protein posttranslational modification, called protein O-GlcNAcylation, which is
a known intracellular sensor of glucose metabolism and plays an important role in
regulating cellular signaling, transcription, and metabolism. However, little is
known about the function of OGT in the brain. Here, we report that the
CaMKIIalpha promoter-dependent neuronal knockout (KO) of OGT in adult mice led to
short-term overeating, body weight gain, and peripheral insulin resistance. These
phenotype changes were accompanied by marked elevation of serum insulin and
leptin levels and neuronal cell death, including the loss of leptin receptor
expressing neurons, in the hypothalamus. The neuronal OGT KO exacerbated obesity
and insulin resistance induced by high-fat diet. Surprisingly, the peripheral
insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months
after OGT KO, and the mice even showed increased insulin sensitivity several
months later. These findings reveal an important role of neuronal OGT in the
regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
PMID- 29944995
TI - Growth and in vivo stresses traced through tumor mechanics enriched with predator
prey cells dynamics.
AB - Mechanical stress accumulating during growth in solid tumors plays a crucial role
in the tumor mechanobiology. Stresses arise as a consequence of the spatially
inhomogeneous tissue growth due to the different activity of healthy and cancer
cells inhabiting the various districts of the tissue, an additional piling up
effect, induced by stress transferring across the scales, contributing to
determine the total stress occurring at the macroscopic level. The spatially
inhomogeneous growth rates accompany nonuniform and time-propagating stress
profiles, which constitute mechanical barriers to nutrient transport and
influence the intratumoral interstitial flow, in this way deciding the
starved/feeded regions, with direct aftereffects on necrosis, angiogenesis,
cancer aggressiveness and overall tumor mass size. Despite their ascertained role
in tumor mechanobiology, stresses cannot be directly appraised neither from
overall tumor size nor through standard non-invasive measurements. To date, the
sole way for qualitatively revealing their presence within solid tumors is ex
vivo, by engraving the excised masses and then observing opening between the cut
edges. Therefore, to contribute to unveil stresses and their implications in
tumors, it is first proposed a multiscale model where Volterra-Lotka
(predator/prey-like) equations describing the interspecific (environment
mediated) competitions among healthy and cancer cells are coupled with equations
of nonlinear poroelasticity. Then, an experimental study on mice injected
subcutaneously with a suspension of two different cancer cell lines (MiaPaCa-2
and MDA.MB231) was conducted to provide experimental evidences that gave
qualitative and some new quantitative confirmations of the theoretical model
predictions.
PMID- 29944996
TI - Synthesis of cholesterol-based neoglycoconjugates and their use in the
preparation of liposomes for active liver targeting.
AB - Carbohydrate receptors on liver represent attractive targets for receptor
mediated delivery of nanostructured therapeutics. In this study, two new
cholesterol-based glycoconjugates derived from d-galactose and N
acetylglucosamine were synthesized and incorporated into liposomes. 99mTc
Cholesterol-DTPA complex was used for radiolabeling experiments in vivo with high
radiochemical yields and stability. Biodistribution studies confirmed the
targeting of galactosylated liposomes (GalL) to liver cells. These results
indicated that GalL could be considered a promising drug delivery system for
liver diseases therapy.
PMID- 29944997
TI - Synthesis of galacto-oligosaccharides derived from lactulose by wild-type and
mutant beta-galactosidase enzymes from Bacillus circulans ATCC 31382.
AB - Oligosaccharides derived from lactulose (beta-D-Galp-(1 -> 4)-D-Fru) are drawing
more and more attention nowadays because of their strong resistance to gut
digestion, and the interest to discover novel prebiotics. Compared to
galactooligosaccharides, currently known structures of lactulose oligosaccharides
are very limited. In this study, the wild-type beta-galactosidase BgaD-D of
Bacillus circulans ATCC 31382, as well as the derived mutant R484H, were used to
synthesize oligosaccharides from lactulose. In total, 9 oligosaccharide
structures were identified by MALDI-TOF-MS and NMR spectroscopy analysis.
Trisaccharide beta-D-Galp-(1 -> 4)-beta-D-Galp-(1 -> 4)-D-Fru was the major
structure produced by the wild-type enzyme, while the R484H mutant showed a
preference for synthesis of beta-D-Galp-(1 -> 3)-beta-D-Galp-(1 -> 4)-D-Fru. Our
study greatly enriched the structural information about oligosaccharides derived
from lactulose.
PMID- 29944998
TI - Long-Term Outcomes After Carotid Endarterectomy: The Experience of an Average
Volume Surgeon.
AB - BACKGROUND: Long-term outcome data for patients undergoing carotid endarterectomy
(CEA) are lacking. As most of the published literature on CEA outcomes has been
from high-volume providers, we wanted to investigate the outcomes of an average
volume cerebrovascular neurosurgeon. METHODS: We reviewed a single neurosurgeon's
experience with CEA focusing on long-term outcomes. Most procedures (99.0%) were
performed with primary closure of the arteriotomy. RESULTS: We studied 192 CEAs
performed between 1998 and 2017, 77% for symptomatic disease. Two patients (1%)
experienced immediate postoperative stroke. During an average follow-up of 53
months (range, 0-205 months), 2 more patients (1%) experienced ipsilateral
carotid circulation stroke, and 5 patients (2.6%) experienced ipsilateral
transient ischemic attacks. Five patients (2.6%) experienced contralateral
transient ischemic attacks, and 6 (3.1%) experienced contralateral stroke. There
were also 3 cases of (1.6%) hemorrhagic stroke and 6 cases (3.1%) of
vertebrobasilar circulation stroke. The rate of ipsilateral stroke-free survival
was 98.4% at 5 years post-CEA, 97.9% at 10 years post-CEA, and 97.9% at 15 years
post-CEA. The rate of ipsilateral restenosis-free survival was 97.9% at 5 years
post-CEA, 96.8% at 10 years post-CEA, and 96.8% at 15 years post-CEA. Six
patients (3.1%) experienced restenosis >70% during follow-up. Two of these
patients underwent carotid artery stenting. Almost all patients (>95%) were
maintained on an antiplatelet medication and statin. CONCLUSIONS: In the hands of
an average-volume cerebrovascular neurosurgeon, CEA can provide durable
protection from recurrent stroke in the ipsilateral carotid distribution that
extends beyond 15 years. Thus, this procedure should be considered the gold
standard against which other revascularization modalities should be evaluated.
PMID- 29945000
TI - Coil Embolization Results of the Ruptured Proximal Posteriori Inferior Cerebellar
Artery Aneurysm: A Single-Center 10 Years' Experience.
AB - OBJECTIVE: To report a single-center experience with endovascular treatment of
ruptured proximal posterior inferior cerebellar artery (PICA) aneurysms. METHODS:
Between January 2007 and December 2016, among 1403 patients with aneurysmal
subarachnoid hemorrhage, 15 with ruptured proximal PICA aneurysms underwent
endovascular embolization at our institution. Aneurysmal obliteration with a
single microcatheter was performed in 9 patients. Additional microcatheter or
stent-assisted coil embolization was performed in 4 patients and parent artery
occlusion in 2 patients. RESULTS: Immediate angiographic results showed 10
complete occlusions (66.7%, 10/15). Five patients showed incomplete occlusion
(remnant neck in 4 patients, remnant aneurysm in 1). Of those, 2 patients
experienced recurrence and required conversion to microsurgical clipping. The
remaining 2 patients remained in relatively stable condition. Procedure-related
complications occurred in 3 patients (20%, with thromboembolic complications in 2
patients and intraprocedural rupture in 1). Clinical outcome was excellent:
Glasgow Outcome Score 4 or 5 in 12 of 15 patients (80%). There was no rebleeding
during follow-up. CONCLUSIONS: Ruptured proximal PICA aneurysms may be
effectively treated with endovascular coil embolization. A variety of coil
embolization techniques are required to obliterate an aneurysm without parent
artery occlusion. Given that recurrence is possible, follow-up is required.
Surgical clipping can be performed for recurrence with a relatively low risk of
complications, because the aneurysm is unruptured. Coil embolization of a
proximal PICA aneurysm in the acute phase can be a good treatment modality with
good patient outcomes.
PMID- 29944999
TI - Safety and Efficacy of Flow Diverter Treatment for Blood Blister-Like Aneurysm: A
Systematic Review and Meta-Analysis.
AB - OBJECTIVE: To clarify the safety and efficacy of flow diverter (FD) treatment for
blood blister-like aneurysm (BBA) through a systematic review and literature
analyzing perioperative and long-term clinical and angiographic outcomes.
METHODS: We performed a comprehensive review of the current literature for
studies with >2 patients related to FD treatment of BBAs published. A random
effects meta-analysis was used to pool the following outcomes: complete
occlusion, technical success, aneurysm recurrence, rebleeding, perioperative
mortality, perioperative stroke, procedure-related morbidity and mortality, long
term neurological morbidity and mortality, and overall good neurologic outcome.
RESULTS: We included 15 noncomparative studies with a total of 165 target BBAs.
Complete occlusion rates were 72% (95% confidence interval [CI], 0.59-0.85).
Recurrence occurred in 13% (95% CI, 0.04-0.29) and rebleeding in 3% (95% CI,
0.02 to 0.07) of patients. Procedure-related morbidity and mortality were 26%
(95% CI, 0.19-0.33) and 3% (95% CI, -0.01 to 0.07), respectively. The rate of
long-term good outcomes was 83% (95% CI, 0.77-0.89). Subgroup analysis indicated
that a single FD strategy for BBA seemed to have a higher rate of good outcomes
compared with an overlapped FD strategy (89.9% vs. 61.9%; odds ratio, 1.42; 95%
CI, 1.25-14.98, P = 0.02). Complete occlusion rate and procedure-related
morbidity rate did not see any significant difference between these 2 strategies.
CONCLUSIONS: Our meta-analysis suggests that in selected cases, FD can be safe
and effective. A single FD strategy may result in a higher rate of good outcomes
compared with an overlapped FD strategy. Ultimately, treatment of BBA should be
considered on a case-by-case basis to maximize patient benefits and limit the
risk of perioperative complications.
PMID- 29945001
TI - Interventions for the Treatment of Craniopharyngioma-Related Hypothalamic
Obesity: A Systematic Review.
AB - OBJECTIVE: Craniopharyngiomas (CPs) and their treatment are associated with
hypothalamic damage that causes hypothalamic obesity (HO) in 30%-70% of cases.
Thus, there is ongoing research regarding tangible solutions for HO, because
these patients have unrelenting resistance to basic weight-loss interventions.
This review aims to summarize the interventions that are used to treat CP-related
HO (CP-HO), including pharmacotherapy and bariatric surgery. METHODS: The
Cochrane Library, EMBASE, and PubMed databases were searched up to June 2017 for
relevant reports. Two reviewers conducted independent evaluations of the studies
identified. RESULTS: Eighteen articles were included in the systematic review,
with 3 reports describing pharmacotherapy in randomized controlled trials and 15
reports describing bariatric surgery. Although several studies described
effective interventions for treating CP-HO, the evidence base was limited by its
low quality and our inability to perform a meta-analysis, which was related to a
lack of adequate or integrated data. CONCLUSIONS: Octreotide appears to be a
preferred treatment for patients with CP-HO, based on limited data. Gastric
bypass surgery may also be suitable for select patients with CP-HO, based on a
review of various procedures in this setting. Microsurgical preservation of the
hypothalamic structures is mandatory to decrease CP-HO-related morbidity and
mortality. Further studies with adequate analytical power and sufficient follow
up are needed to identify effective strategies for CP-HO treatment.
PMID- 29945002
TI - Accuracy of Screw Placement and Clinical Outcomes After O-Arm-Navigated
Occipitocervical Fusion.
AB - OBJECTIVE: This study aimed to evaluate the accuracy of screw placement and
clinical outcomes in patients undergoing occipitocervical fusion. METHODS:
Patients who underwent occipitocervical fusion with O-arm-based navigation were
retrospectively reviewed between January 2015 and December 2017. The patients'
characteristics, clinical and radiographic outcomes, and surgical complications
were recorded and analyzed. Cervical screw insertion accuracy was evaluated using
the Richter scale. RESULTS: Thirty consecutive patients (11 male and 19 female)
with an average treatment age of 40.03 +/- 15.19 years were studied. The most
common cause was atlantoaxial instability combined with Chiari malformation
(63.33%). Weakness (76.67%) and paresthesia (70.00%) were the most common
symptoms. Eighty-six occipital and 139 cervical screws were placed using an O-arm
assisted navigation system. In total, 130 (93.53%) cervical screws were graded as
group A and 9 (6.47%) as group B. The optimal accuracy rate was 88.41% (61 of 69
screws) in the first 15 patients and 98.57% (69 of 70 screws) in the subsequent
15 patients. The mean follow-up time was 7.50 +/- 5.70 months. The mean Japanese
Orthopedic Association scores were 13.30 +/- 2.41 preoperatively and 15.30 +/-
1.60 at final follow-up (P < 0.001), and the mean recovery rate in the Japanese
Orthopedic Association score was 53.26 +/- 33.82%. Clinical improvement was seen
in 25 patients (83.33%), whereas no change was observed in 5 patients (16.67%).
The overall complication rate was 6.67% (2/30), with 1 intraoperative vertebral
artery injury and 1 postoperative screw loosening. CONCLUSION: Occipitocervical
fusion with O-arm-based navigation is effective and safe for treating instability
of the craniovertebral junction. Intraoperative navigation can help surgeons
insert screws accurately.
PMID- 29945004
TI - Recurrence in 787 Patients with Chronic Subdural Hematoma: Retrospective Cohort
Investigation of Associated Factors Including Direct Oral Anticoagulant Use.
AB - OBJECTIVE: Chronic subdural hematoma (CSDH) is a highly recurrent disorder.
Although some predictors including the use of antithrombotic agents such as
aspirin and warfarin have been proposed, the pathogenic mechanism involved
remains unclear. Moreover, the link between direct oral anticoagulant (DOAC)
agent use and CSDH recurrence has not been reported. The aim of this study was to
investigate factors including DOAC use that could potentially be associated with
CSDH recurrence. METHODS: The authors analyzed 787 patients with CSDH who
underwent surgery for CSDH with 1 burr-hole irrigation at Baba Memorial Hospital
from January 2012 to November 2017. The patients were divided into recurrence and
nonrecurrence groups and anticoagulant, antiplatelet, and control groups.
Recurrence was defined as ipsilateral hemorrhage within 90 days from the original
operation. Variables with P < 0.1 in the univariate analysis were included in a
multivariate logistic regression model. RESULTS: CSDH recurrence was observed in
12.2% of patients, and significantly more men (80.2%) than women experienced
recurrence. Age, sex, and warfarin use were entered in the multivariate analysis,
and it was revealed that age and male sex were independently associated with CSDH
recurrence. Antithrombotic agent use including use of DOACs was not associated
with increased CSDH recurrence. CONCLUSIONS: The present study found that age and
male sex were independently associated with CSDH recurrence, while the use of
antithrombotic agents was not.
PMID- 29945003
TI - Predicting Current Thresholds for Pyramidal Tract Activation Using Volume of
Activated Tissue Modeling in Patients Undergoing Deep Brain Stimulation Surgery.
AB - BACKGROUND: The volume of activated tissue (VTA) model attempts to represent in 3
dimensions the diffusion of the current provided by the deep brain stimulation
lead on brain structures. The objective of the present study was to assess the
correlations among the VTA, activation of the corticospinal tract, and the
intraoperative side effect (ISE) threshold. METHODS: This double-blind, single
center study was performed between September 2016 and July 2017. We identified 2
groups for statistical analysis: the entire study population and a subset of
patients with additional diffusion tensor imaging (DTI) data for determining the
location of the pyramidal tract. We determined the intensity threshold at which
the VTA reached the border of the target nucleus (referred to as the VTAn) and
the intensity threshold when the VTA reached the pyramidal tract (VTAndti). In
each group of patients, we studied the correlations between the ISE threshold and
the VTAn or VTAndti threshold. RESULTS: Fifteen patients were included in the
study. In both groups, there was a significant correlation between the VTA
intensity threshold and the ISE threshold (P = 0.018; r = 0.31 for VTAn in the
entire study population). The correlation was stronger in the subset of patients
with valid tractography data (P = 0.002; r = 0.5 for VTAndti). CONCLUSIONS: The
present study is the first to show a relationship between the intensity threshold
as determined by the use of the VTA and the ISE threshold. The correlation
between the clinical features and the VTA appears to be stronger in the model
based on a combination of high-resolution anatomic data and interpretable DTI
data.
PMID- 29945005
TI - Risk Factors Associated with Neurologic Deterioration After Combined Direct and
Indirect Revascularization in Patients with Moyamoya Disease on the East Coast of
China.
AB - OBJECTIVE: Neurologic deterioration is the primary distinctive complication after
revascularization surgery in patients with moyamoya disease (MMD). The present
study investigated the risk factors for neurologic deterioration after combined
direct and indirect revascularization in patients with MMD. METHODS: A
retrospective review of 123 patients with MMD undergoing 138 combined direct and
indirect revascularization procedures was performed. Demographics, clinical
manifestation, medical history, neurologic deterioration complications, and
relevant information of the operation were recorded. RESULTS: There were 25
(18.12%) postoperative neurologic deterioration complications (13 reversible
neurologic deficits, 9 infarctions with neurologic sequelae, and 3 hemorrhages).
Preoperative multiple symptom episodes and one-staged bilateral revascularization
were significantly correlated with postoperative neurologic deterioration
complications (P < 0.05 and P < 0.01, respectively). The incidence rate (26.39%)
of postoperative neurologic deterioration in ischemic MMDs was significantly
greater than hemorrhagic MMDs (7.69%; P < 0.01) In total, 34.78% of patients with
transient ischemic attack onset and 22.45% of patients with infarction onset
suffered from postoperative neurologic deterioration, and there was no
significant difference between them (P > 0.05). Postoperative neurologic
deterioration complications had no significant correlation with sex, age at the
time of surgery, type of surgical procedure, unilateral MMD or not, interval
between the last attack and operation, and history of thyroid disease,
hypertension, and autoimmune disease. CONCLUSIONS: Preoperative multiple symptom
episodes and one-staged bilateral revascularization are risk factors associated
with postoperative neurologic deterioration in patients with MMD. Therefore, 2
unilateral revascularization procedures performed successively rather than one
staged bilateral revascularization procedures should be performed in patients
with bilateral MMD.
PMID- 29945006
TI - To evaluate the Changes of the expression and activity of Phosphodiesterase V in
the Basilar Artery Before and After Cerebral Vasospasm in Rabbits model.
AB - OBJECTIVE: To examine the changes of expression and activity of phosphodiesterase
V (PDEV) in the basilar artery following cerebral vasospasm (CVS) after
subarachnoid hemorrhage (SAH) in rabbits model. METHODS: A rabbit model of CVS
after SAH was constructed by twice blood injection into the cisterna magna. The
subjects were divided into the following groups: blank control, tested control
and SAH-treated group. Transcranial doppler (TCD) and selective vertebrobasilar
digital subtraction angiography (DSA) were performed on day 5 to determine the
changes of CVS. Changes of PDEV expression and activity were examined. RESULTS:
Severity of CVS could be accurately determined by DSA and TCD. Narrowing of the
basilar artery was observed at 24 h after second blood injection into the SAH
treated rabbits, along with delayed imaging and increased blood flow rate. These
changes reached peak levels on day 3 post-surgery and were maintained up until
day 7, after which they gradually returned to normal levels on day 11. PDEV
expression was significantly increased in the basilar artery of rabbits in the
SAH group. The concentration and activity of PDEV began to increase at 24 h post
surgery, peaked at day 3-day 7, and gradually decreased to normal levels on day
11. CONCLUSIONS: Increased basilar artery blood flow, narrowing of the basilar
artery, and PDEV expression in the basilar artery could be detected using TCD,
DSA and immunohistochemistry, respectively, suggesting that PDEV is associated
with the development of CVS following SAH in rabbits.
PMID- 29945007
TI - Sharpening the Surgeon's Knife: Value of Extent of Resection for Glioma in
Molecular Age.
PMID- 29945008
TI - Correlation of Interpedicular Distance with Radiographic Parameters, Neurologic
Deficit, and Posterior Structures Injury in Thoracolumbar Burst Fractures.
AB - OBJECTIVE: To correlate interpedicular distance (IPD) with radiographic
parameters, neurologic deficit, and posterior structures injury in patients with
thoracolumbar burst fractures. METHODS: A total of 103 patients with a
thoracolumbar burst fracture retrospectively reviewed. IPD was measured from the
medial sclerotic areas of the pedicles on anteroposterior plain radiographs. Data
on local kyphosis (LK), the ratio of anterior to posterior vertebral height (A/P
ratio), loss of vertebral body height (LOVBH), spinal canal stenosis (SCS),
neurologic status, and injuries to posterior structures (lamina, posterior
ligamentous complex, and facet joint) were correlated with IPD using correlation
analysis. Logistic regression analysis was used to determine the threshold of IPD
predictive of neurologic deficit and posterior structure injury. RESULTS: Of the
103 patients, 98 (95.15%) presented with increased IPD, ranging from 1.41% to
41.53% (mean, 10.92 +/- 3.37%). Regarding radiographic parameters, both LK and
SCS were linearly correlated with IPD. There was a significant correlation
between IPD and neurologic status; logistic regression analysis identified an IPD
increase of >20% as an indicator of neurologic deficit. In addition, both facet
joint injury and lamina fracture were associated with IPD, with an IPD increase
>15% as an indicator of facet joint injury and an IPD increase >20% a predictor
of lamina fracture. CONCLUSIONS: Our results indicate that IPD is correlated with
LK, SCS, neurologic status, facet joint injury, and lamina fracture. Our data
demonstrate that IPD measured from plain radiographs is a reliable indicator for
assessment of thoracolumbar burst fractures.
PMID- 29945009
TI - Fusion Techniques Are Related to a Lower Risk of Reoperation in Lumbar Disc
Herniation: A 5-Year Observation Study of a Nationwide Cohort in Taiwan.
AB - OBJECTIVE: Lumbar disc herniation (LDH) is a common spinal problem, with
reoperation rates of 6%-24%. Although different surgical techniques are used for
treatment, there is still debate regarding whether fusion techniques can reduce
the reoperation rate in patients with LDH. METHODS: This retrospective study used
a 5-year nationwide database to analyze reoperation rates in Taiwan. Patient age
groups (>=20 and <90 years) treated by index surgery and reoperation for LDH were
identified. Four surgical procedures were included in the analysis: discectomy
(DC), anterior lumbar fusion with DC (FA + DC), posterior lumbar fusion (FP), and
posterior lumbar fusion with DC (FP + DC). RESULTS: There were 1743 index
surgeries between 2008 and 2012, with 184 (10.56%) reoperations. Index surgery DC
had the highest reoperation rate (n = 121, 20%). The reoperation risk was
significantly lower for patients undergoing fusion procedures (FA + DC vs. DC
[hazard ratio (HR), 0.24; 95% confidence interval (CI), 0.12-0.47; P < 0.01], FP
versus DC [HR, 0.17; 95% C, 0.09-0.33; P <0.01], FP + DC versus DC [HR, 0.31; 95%
CI, 0.22-0.44; P < 0.01]). Fusion procedures had significantly higher treatment
costs compared with DC (FA + DC vs. FP vs. FP + DC vs. DC: 5851.74 +/- 4808.94
vs. 5116.88 +/- 3428.97 vs. 4782.16 +/- 2902.19 vs. 3846.79 +/- 3584.45 U.S.
dollars/patient, respectively; P < 0.0001). CONCLUSIONS: Among surgical
procedures for LDH, fusion techniques are related to lower reoperation rates
compared with discectomy, but at the expense of higher medical costs.
PMID- 29945010
TI - The Introduction of Innovations in Neurovascular Care: Patient Selection and
Randomized Allocation.
AB - Most neurovascular innovations have been introduced by using case series followed
by observational studies. A better approach would be a pragmatic randomized
trial. Two important aspects of trial design, patient selection and randomized
allocation, remain poorly understood. We discuss the role trial methodology can
play in the protection of patients being offered innovative treatments.
PMID- 29945011
TI - Cement Distribution Patterns Are Associated with Recompression in Cemented
Vertebrae After Percutaneous Vertebroplasty: A Retrospective Study.
AB - OBJECTIVE: To reevaluate the cement distribution patterns and further investigate
associations between cement distribution patterns and the occurrence rates of
recompression in cemented vertebrae after percutaneous vertebroplasty (PVP) for
osteoporotic vertebral compression fractures. METHODS: Two hundred twenty-four
patients with a mean age of 71.9 years were enrolled and treated with single
level PVP between June 2012 and July 2015. The mean follow-up time was 16.5
months. Data from medical records and radiographs were collected and analyzed.
Cement distribution patterns were divided into 4 cement distribution patterns
extending from the traditional 2 patterns: interlocked solid pattern (LS) and
uninterlocked solid pattern (ULS); contiguous trabecular pattern (CT) and
discontiguous trabecular pattern (DCT). Differences in treatment efficacy and the
occurrence rates of recompression in cemented vertebrae were compared for both
groups using the Wilcoxon rank sum test and chi-squared test. RESULTS: Thirty
seven patients who underwent PVP developed recompression in cemented vertebrae.
Recompression in cemented vertebrae was significantly more frequent in the ULS
and DCT groups than in the LS and CT groups (P < 0.05 or 0.001), with the Visual
Analogue Scale score at the time of final follow-up was also significantly higher
in the ULS and DCT groups (P < 0.001). CONCLUSIONS: Significant associations were
found between cement distribution patterns and recompression in cemented
vertebrae, which affected the clinical outcome in patients after PVP. A higher
incidence of recompression in cemented vertebrae was seen in patients with
treated vertebrae exhibiting ULS pattern or DCT pattern.
PMID- 29945012
TI - Possible Implications of Medical Treatment in Subdural Hematomas in Developing
World.
PMID- 29945013
TI - Microsurgical Management of Vascular Malformations of the Pineal Region.
AB - BACKGROUND: Vascular pineal malformations are rare and technically demanding
lesions. Because the locations of these lesions, endovascular techniques and
radiosurgery have been increasingly used in the recent decades to accomplish safe
occlusion. Nevertheless, microsurgical treatment may be required sometimes.
METHODS: We present a retrospective review of the vascular pineal malformations
operated by the senior author. Moreover, we report illustrative cases for the
various types of vascular lesions with a careful analysis of the different
microsurgical stages. RESULTS: Eighteen patients with pineal vascular lesions
were operated on between 1980 and 2015: 6 patients had vein of Galen
malformations, 5 plexiform arteriovenous malformations, 6 cavernous
malformations, and 1 patient had a ruptured medial posterior choroidal artery
aneurysm. A complete resection and occlusion was possible in all vascular
malformations. CONCLUSIONS: The pineal region is an infrequent but challenging
location for vascular lesions. A careful and stepwise operative strategy for the
different types of vascular lesion is paramount to accomplish an effective and
safe microsurgical treatment when other alternatives fail or are not available.
PMID- 29945014
TI - A theoretical study on the cross-talk of stress regulatory pathways in root
cells.
AB - The plants developed more dedicated regulatory pathways than the animals did to
response various environment stresses, since they could not run away. The cross
talk among the pathways generally introduce non-trivial regulatory behaviors,
from which the plants may benefit. For better understanding the regulatory
mechanism due to cross-talk, we study in this work two entangled stress
regulatory pathways in root cells. A quantitative model of the regulatory network
is constructed in the simplest fashion. An analytic parameter-free approach is
then employed to analyse the response tendencies. It leads us to a simple
constraint on the non-linear regulatory exponents. Under the constraint, a
transition to the non-monotonic growth inhibition happens at finite concentration
of ABA, due to which the plants could survive from cold/heat stress. The
parameter-free tendency analysis would also be applied to further experiments,
especially in the case of insufficient data for multi-parameter fitting.
PMID- 29945015
TI - Solvothermal-assisted evaporation-induced self-assembly of ordered mesoporous
alumina with improved performance.
AB - A solvothermal-assisted evaporation-induced self-assembly (SA-EISA) approach has
been developed for the synthesis of ordered mesoporous alumina (OMA) materials
with high thermal stability and improved performance in catalysis. In
conventional EISA process, the evaporation step is accompanied by the hydrolysis
of organic aluminum precursors, thus the evaporation conditions have significant
influences on the reaction and the final structure of OMA. In our approach, the
solvothermal treatment step promotes the complete hydrolysis of aluminum
precursors and produces partially condensed cluster-like aluminum hydroxyl
species, which allows the formation of OMA in a broad range of evaporation
conditions. Compared to mesoporous alumina obtained by conventional EISA process,
OMA materials prepared by SA-EISA approach exhibit higher specific surface area,
pore volume and thermal stability. When used as supporting materials for vanadium
oxide catalyst, OMA materials obtained by the SA-EISA approach exhibit excellent
activity, selectivity and stability for ethylbenzene dehydrogenation with carbon
dioxide as a mild oxidant. Our contribution has provided new understanding in the
synthesis of OMA materials with improved performance for catalytic applications.
PMID- 29945016
TI - Bridging the gap: Optimized fabrication of robust titania nanostructures on
complex implant geometries towards clinical translation.
AB - Electrochemically anodized titanium surfaces with titania nanostructures (TNS;
nanopores, nanotubes, etc.) have been widely applied as therapeutic bone/dental
implant modifications. Despite the numerous advancements in the field of
electrochemical anodization (EA), in terms of translation into the current
implant market, research gaps in this domain include the lack of fabrication
optimization, performed on a substrate of conventional implant surface/geometry,
and inadequate mechanical stability. In the current study, we investigate the
role of substrate pre-treatment on achieving desired nanotopographies for the
purpose of reproducing optimized nanostructures on the complex geometry of
commercial implant surfaces, as well as in-depth mechanical stability testing of
these nano-engineered coatings. The results confirmed that: (a) substrate
polishing/smoothening may be insignificant with respect to fabrication of well
ordered and high quality TNS on micro-rough implants with preserved underlying
micro-roughness; (b) optimized outcomes can be successfully translated onto
complex geometries characteristic of the current implant market, including dental
implant abutments and screws (also applicable to a wider implant market including
orthopaedics); (c) mechanical stability testing revealed improved modulus and
hardness values as compared to conventional nanotubes/pores. We believe that such
optimization advances the existing knowledge of titanium anodization and anodized
implants towards integration into the current implant market and successful
clinical translation.
PMID- 29945017
TI - Wormlike micelle formation of novel alkyl-tri(ethylene glycol)-glucoside
carbohydrate surfactants: Structure-function relationships and rheology.
AB - Carbohydrates are appealing non-ionic surfactant head-groups as they are
naturally abundant, generally biocompatible and biodegradable, and readily
functionalized. Here, seven novel carbohydrate based surfactants (CBS) have been
synthesized that contain a tri-ethylene glycol (TEG) linker between a glucose
head-group and alkyl tail-group, with linear saturated (C8-18) and unsaturated
(C18:1) alkyl chains. The aqueous adsorption and self-assembly of these
surfactants was explored using tensiometry and small- and ultra-small-angle
neutron scattering (SANS and USANS). With SANS we observed elongation from
spherical to cylindrical micelles with increasing alkyl chain length. C16 and C18
chains exhibited pronounced Krafft points, yet formed worm-like micelles as
single components upon heating to 43 and 48 degrees C respectively. The
introduction of mono-unsaturation in the form of a C18:1 chain reduced the Krafft
point and gave a surfactant that produced worm-like micelles in water without
additives at room temperature. We also observed micellar elongation for C12 and
C14 chains at 50 degrees C due to dehydration of the TEG linker. The room
temperature worm-like micelles were further characterized using rheo-SANS and
rheology, revealing the C18:1 surfactant to exhibit near ideal Maxwell behavior
at low concentrations (2.9 wt.%). These results provide insight into structure
function relationships for CBS, and demonstrate a promising molecular candidate
for the formation of viscoelastic worm-like micellar solutions.
PMID- 29945018
TI - Controlled growth of gamma-MnO2 nanoflakes on OMS-2 for efficient decomposition
of organic dyes in aqueous solution via peroxymonosulfate activation.
AB - The development of green and efficient catalysts for peroxymonosulfate (PMS)
activation and abatement of organic pollutants in wastewater is of significant
practical interest. In this paper, the three-dimensional mixed manganese oxides
of OMS-2 and gamma-MnO2 were fabricated through a simple refluxing method from
KMnO4 and MnSO4. It was found that growth of gamma-MnO2 nanoflakes on OMS-2 can
be controlled by the concentration of MnSO4. The catalysts not only have many
excellent structural properties such as interconnected network and highly exposed
active sites, but also show the high ratio of low valent manganese species. In
particular, the catalysts exhibited much higher efficiency for Acid Orange 7
degradation in the presence of PMS than pure OMS-2 or gamma-MnO2. The oxidation
of Mn(III) species by PMS occurs in the system with the formation of sulfate and
hydroxyl radicals contributed to the dye degradation. Moreover, the catalysts
showed good stability and reusability during four consecutive cycles. Thus, the
environmental friendly mixed manganese oxides of gamma-MnO2 and OMS-2 with low
cost, facile synthesis process and high efficiency are very promising catalysts
for PMS activation and pollutants degradation.
PMID- 29945019
TI - Biocompatible gadolinium oxide nanoparticles as efficient agent against
pathogenic bacteria.
AB - The inappropriate and surfeit use of antibiotics have generated a hunt for safe
and alternative antimicrobial agents against pathogenic bacteria. With the
advancement in nanoscience and nanotechnology, promising opportunities for
examining the bacterial effect of metal nanoparticles were demonstrated in
literature. Focusing on this, our present study presentssynthesis of l-ascorbic
coated gadolinium oxide nanoparticles via a simple precipitation route. Their
complete characterization and detailed stability studies were carried out. The
obtained nanoparticles were characterized by Fourier transform infrared (FT-IR)
spectroscopy, confirming that l-ascorbic acid onto the surface of nanoparticles.
The size and morphology were analyzed by Transmission electron Microcopy (TEM)
and Field emission scanning electron microscopy (FE-SEM) which reveals their
spherical nature. The stability studies were performed to know about their
chemical and colloidal stability. The synthesized nanoparticles were found to be
non-toxic to HaCaT cells upto the concentration of 125 ug/mL. The antimicrobial
effect of nanoparticles was analyzed against three bacterial strains; E. coli, S.
aureus and S. typhimurium. To summarize, the synthesized nanoparticles are found
to be safe and protective against pathogenic bacteria. They further can be
explored in biomedical applications considering their non-toxic nature.
PMID- 29945020
TI - Photocatalytic degradation of ibuprofen over BiOCl nanosheets with identification
of intermediates.
AB - Photocatalysis directed at the removal of persistent organic pollutants,
including pharmaceuticals, has been the subject of intense recent research.
Bismuth oxychloride (BiOCl) has emerged as a potential alternative to traditional
photocatalysts and has shown competitive removal efficiencies. However, pathways
responsible for BiOCl photodegradation have not been well characterized. The
present work is the first to determine, using LC-MS/MS analysis, the pathways by
which BiOCl removes ibuprofen (IBP) from water. HPLC-DAD and LC-MS/MS analyses
show that BiOCl converts IBP to two primary photochemical products, 4
isobutylacetophenone (IBAP) and 1-(4-isobutylphenyl)ethanol (IBPE). The
reactivity for BiOCl is attributed to interactions of the carboxylic acid group
of IBP with holes in the valence band. Hydroxylated-IBP was not detected in BiOCl
photocatalytic degradation experiments which would be expected in a process
driven by the formation and reactivity of reactive oxygen species. These data
were used to formulate a photocatalytic degradation pathway for IBP and highlight
the importance of studying both primary and secondary degradation reactions for
photocatalytic studies.
PMID- 29945021
TI - Hydrolysis reaction promotes changes in coordination mode of Ru(II)/acylthiourea
organometallic complexes with cytotoxicity against human lung tumor cell lines.
AB - In this study, Ru(II)-arene complexes with acylthiourea ligands of the type
[Ru(eta6-p-cymene)(PPh3)(T)Cl]PF6(1-5) and [Ru(eta6-p-cymene)(PPh3)(T)]PF6(1a,
4a), where PPh3 = triphenylphosphine and T = N-acyl-N'(monosubstituted)thiourea,
were synthesized and characterized, and their cytotoxic properties were also
evaluated. 1a and 4a were obtained from the hydrolysis reaction of 1 and 4. All
complexes showed unusual coordination modes for acylthiourea ligands, which are
coordinated in a monodentate fashion (S) in 1-5, while they found to be bidentate
(S,N), in 1a and 4a. To the best of our knowledge, 1a and 4a are the first
crystallographically reported ruthenium compounds with acylthiourea coordinated
via S and N(amide) atoms. The cytotoxicity of the compounds was evaluated in
human lung cells, A549 and MRC-5. The IC50 values ranging from 0.25 to 0.61 MUM
after 48 h incubation in lung cancer cells indicate that the compounds showed
high cytotoxicity with values significantly lower than the reference drug,
cisplatin (11.84 MUM). Interaction studies were carried out using human serum
albumin (HSA) and DNA. All complexes showed similar cytotoxic activity, however
complex 1a, which is the hydrolysis product of 1, presented the highest activity
and selectivity among all seven compounds synthesized here. Complexes 1 and 1a
inhibited the colony formation decreasing the colony size and inducing morphology
changes in A549 cells. These complexes induced apoptosis cell death and promoted
cell cycle arrest in the Sub-G1 phase with a decrease in the cell number at the S
phase.
PMID- 29945022
TI - Interactions between metal binding viral proteins and human targets as revealed
by network-based bioinformatics.
AB - The role of metal ions in virus-host interactions is largely unknown. In the
present computational study, the putative zinc, manganese, magnesium, and iron
metalloproteomes of 226 different viruses were identified and then the human
proteins interacting the viral metalloproteomes were retrieved through network
based bioinformatics. Protein features such as abundance, function and
structurally disorder were classified according to the metal type bound to viral
proteins. Likely perturbations of host cellular metal homeostasis by viral metal
binders are also discussed. Furthermore, possible molecular linkage between the
human proteome infected by viral metalloproteins with twelve neurological
disorders was examined by in silico gene network analysis.
PMID- 29945023
TI - Selective Cu(I) complex with phosphine-peptide (SarGly) conjugate contra breast
cancer: Synthesis, spectroscopic characterization and insight into cytotoxic
action.
AB - The main disadvantage of conventional anticancer chemotherapy is the inability to
deliver the correct amount of drug directly to cancer. Those molecular delivering
systems are very important to destroy cancer cells selectively. Herein we report
synthesis of phosphine-peptide conjugate (Ph2PCH2-Sar-Gly-OH, PSG) derived from
SarGly (sarcosine-glycine), which can be easily exchanged to other peptide
carriers, its oxide (OPh2PCH2-Sar-Gly-OH, OPSG) and the first copper(I) complex
([CuI(dmp)(P(Ph)2CH2-Sar-Gly-OH)], 1-PSG, where dmp stands for 2,9-dimethyl-1,10
phenanthroline). The compounds were characterized by elemental analysis, NMR (1D,
2D), UV-Vis spectroscopy and DFT (Density Functional Theory) methods. PSG and 1
PSG proved to be stable in biological medium in the presence of atmospheric
oxygen for several days. The cytotoxicity of the compounds and cisplatin was
tested against cancer cell lines: mouse colon carcinoma (CT26; 1-PSGIC50 = 3.12
+/- 0.1), human lung adenocarcinoma (A549; 1-PSGIC50 = 2.01 +/- 0.2) and human
breast adenocarcinoma (MCF7; 1-PSGIC50 = 0.98 +/- 0.2) as well as against primary
line of human pulmonary fibroblasts (MRC-5; 1-PSGIC50 = 78.56 +/- 1.1).
Therapeutic index for 1-PSG (MCF7) equals 80. Intracellular accumulation of 1-PSG
complex increased with time and was much higher (96%) inside MCF7 cancer cells
than in normal MRC5 cells (20%). Attachment of SarGly to cytotoxic copper(I)
complex via phosphine motif improved selectivity of copper(I) complex 1-PSG into
the cancer cells. Precise mechanistic study revealed that the 1-PSG complex
causes apoptotic cells MCF7 death with simultaneous decrease of mitochondrial
membrane potential and increase of caspase-9 and -3 activities. Additionally, 1
PSG generated high level of reactive oxygen species that was the reason for
oxidative damages to the sugar-phosphate backbone of plasmid DNA.
PMID- 29945025
TI - Comparison of lactate and beta-hydroxybutyrate in the treatment of concanavalin-A
induced hepatitis.
AB - Simple metabolites released during physical exercise and fasting like lactate
(Lac) and beta-hydroxybutyrate (BHB) have recently been shown to possess anti
inflammatory properties. However, the effects of these metabolites in immune
mediated hepatitis are still unknown. Accordingly, we investigated the role of
Lac, BHB and their combination on experimentally induced hepatic inflammation.
Adult male mice were administered concanavalin A (Con A, 15 mg/kg, intravenous)
for 12 h. In the treatment groups, mice were treated 1 h after Con A-intoxication
with Lac (500 mg/kg, intraperitoneal), BHB (300 mg/kg, intraperitoneal) and their
combination. The results demonstrated that Lac and BHB, especially when combined
together, alleviated Con A-induced hepatocellular injury (ALT, AST and LDH) and
necrosis (hematoxylin-eosin and electron microscopy). These beneficial effects
correlated with attenuating Con A-induced elevation in hepatic oxidative stress
parameters (MDA and NOx). Mechanistically, administration of Lac and BHB led to
inhibition of Con A-induced phosphorylation of JNK and AMPK proteins in the liver
to the same extent. These effects were concordant with curbing Con A-mediated
overexpression of the pro-inflammatory cytokines TNF-alpha, IL-6 and IL-12 and
activation of the transcription factor NF-kappaB. The marked anti-inflammatory
properties of combining Lac and BHB were attributed to their cooperation in
repressing immune cells (monocytes and neutrophils) infiltration to the liver.
Unlike BHB, Lac administration markedly induced the reparative STAT3 and ERK
phosphorylation in the livers of Con A-intoxicated mice at the early time point.
In conclusion, the simultaneous use of Lac and BHB might be an auspicious
strategy for limiting immune mediated hepatitis.
PMID- 29945024
TI - Clinical efficacy and safety of CIK plus radiotherapy for lung cancer: A meta
analysis of 16 randomized controlled trials.
AB - OBJECTIVE: Cytokine-induced killer cells (CIK) therapy is the most commonly used
cellular immunotherapy. The CIK plus radiotherapy was clinically used in a wide
range of treatment, but the efficacy of their combination against lung cancer is
not clear yet. Therefore, we systematically evaluated all the related studies to
reveal the combination's clinical efficacy and safety in lung cancer. MATERIALS
AND METHODS: We collected all the studies about CIK plus radiotherapy for lung
cancer in Medline, Embase, Web of Science (ISI), China National Knowledge
Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database
(VIP), Wanfang Database, China Biological Medicine Database (CBM) and Cochrane
Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry
(Chi-CTR), WHO International Clinical Trials Registry Platform (WHO-ICTRP) and US
clinical trials (March 2017). We evaluated their bias risk according to the
Cochrane evaluation handbook of randomized controlled trials (RCTs), extracted
all the data, and synthesized the data using meta analysis. RESULTS: We included
16 RCTs involving 1197 patients with lung cancer, and most trials had unclear
risk of bias. Meta-analysis showed that CIK therapy could increase the objective
response rate (ORR) (1.32, 1.21 to 1.44), the disease control rate (DCR) (1.13,
1.04 to 1.23), the 1-year overall survival (OS) rate (1.38, 1.16 to 1.63) and the
2-year OS rate (1.23, 1.11 to 1.35). DCs-CIK cells increased the 3-year OS rate
(1.66, 1.20 to 2.29). DCs-CIK therapy could increase the CD3+T cells (2.27, 1.47
to 3.06), CD4+T cells (1.28, 0.74 to 1.81), NK cells (2.04, 0.74 to 3.33) and
CD4+/CD8+ T cells ratio (1.20, 0.64 to 1.76) and decrease the CD8+T cells (-0.84,
-1.60 to -0.08). CIK plus radiotherapy had lower risk of leukopenia (0.85, 0.76
to 0.95) and higher risk of fever (5.50, 2.71 to 11.17) than that of radiotherapy
alone. Subgroup analysis showed that CIK plus radiotherapy, mainly three
dimensional conformal radiotherapy (3D-CRT) could increase the ORR, DCR, 1- and 2
year OS rate in non-small cell lung cancer (NSCLC), and only DCR in small cell
lung cancer (SCLC). Compared with CIK plus pure radiotherapy, except for the ORR,
DCR, 1-year OS rate, CIK plus chemoradiotherapy could still increase the 2-year
OS rate. DCs-CIK could increase the ORR, DCR, 1- and 2-year OS rate, CIK cells
could only increase the ORR and the 1-year OS rate. CONCLUSIONS: CIK plus
radiotherapy can improve the clinical response, OS and PFS in lung cancer. It may
have low risk of leukopenia and high risk of fever. CIK plus chemoradiotherapy,
mainly 3D-CRT can improve the clinical response, OS and PFS in NSCLC. DCs-CIK
cells can improve the 1-, 2- and 3-year OS rate, and the 1- and 2-year PFS rate,
and CIK cells only improve the 1-year OS rate. DCs-CIK cells can repair the
antitumor immunity.
PMID- 29945027
TI - Borderline personality disorder features and drinking, cannabis, and prescription
opioid motives: Differential associations across substance and sex.
AB - INTRODUCTION: Drinking motives have shown meaningful associations with borderline
personality disorder (BPD) features. However, it is unknown whether other common
substances of abuse (namely cannabis and prescription opioids) have the same
associations with BPD features. In the present study, we tested associations
between BPD features and motives across three substances: alcohol, cannabis, and
prescription opioids. The purpose of the study was to determine whether BPD
showed similar patterns of associations across drugs, or whether some substances
serve particular functions for individuals with BPD features, and whether this
also varies by sex in a college student sample. METHOD: Five-hundred ninety-four
college students completed online questionnaires measuring demographics,
borderline personality disorder features, substance use, and substance specific
motives for alcohol, cannabis, and prescription opioid use. RESULTS: BPD was most
strongly associated with coping motives across all substances. For both alcohol
and cannabis, this was true for both males and females, along with conformity
motives. For prescription opioids, coping, social, enhancement, and pain motives
were only significantly related to BPD features for females. When compared
statistically, it was found that the associations with coping drinking motives
and opioid pain motives were higher among females. CONCLUSIONS: This pattern of
results suggests that negatively reinforcing motives (coping and conformity) play
a similar functional role in borderline personality and substance use disorder
pathology for alcohol and cannabis, but for prescription opioids the negative
reinforcement motives (coping and pain) were only evident in females.
PMID- 29945026
TI - Nasal vaccination with pneumococcal surface protein A in combination with
cationic liposomes consisting of DOTAP and DC-chol confers antigen-mediated
protective immunity against Streptococcus pneumoniae infections in mice.
AB - Infectious diseases are the second leading cause of death worldwide, suggesting
that there is still a need for the development of new and improved strategies for
combating pathogens effectively. Streptococcus pneumoniae is the most virulent
bacteria causing pneumonia with high mortality, especially in children and the
elderly. Because of the emergence of antibiotic resistance in S. pneumoniae,
employing a serotype-independent mucosal vaccine would be the best approach to
prevent and treat the diseases caused by S. pneumoniae. In this study, we have
developed a pneumococcal nasal vaccine, consisting of pneumococcal surface
protein A (PspA) and cationic liposomes composed of 1,2-dioleoyl-3
trimethylammonium-propane (DOTAP) and cholesteryl 3beta-N-(dimethylaminoethyl)
carbamate (DC-chol) (DOTAP/DC-chol liposome). The efficiency of this cationic
liposome-based PspA nasal vaccine was examined in a murine model of S. pneumoniae
infection. Intranasal vaccination with PspA and DOTAP/DC-chol liposomes conferred
protective immunity against lethal inhalation of S. pneumoniae, improving the
survival rate of infected mice. Moreover, intranasal immunization with PspA and
DOTAP/DC-chol liposomes not only induced the production of PspA-specific IgA and
IgG by both mucosal and systemic compartments but also elicited PspA-specific
Th17 responses, which play a pivotal role in controlling S. pneumoniae infection
by host innate immune response. We further demonstrated that DOTAP/DC-chol
liposomes enhanced PspA uptake by nasal dendritic cells (DCs), which might be a
mechanism for the induction of protective immune responses to S. pneumoniae
infection. These results show that DOTAP/DC-chol liposome would be an efficient
mucosal vaccine system for a serotype-independent universal nasal vaccine against
pneumococcal infection.
PMID- 29945028
TI - Low-frequency electrical stimulation with variable intensity preserves torque.
AB - The neuromuscular electrical stimulation (NMES) parameters that optimally
modulate torque output during prolonged stimulation protocols are not well
established. The purpose of this study was to compare torque output between low
frequency and high-frequency NMES protocols while increasing stimulation
intensity. Eleven healthy young individuals received a repetitive, intermittent
low-frequency (20 Hz) and high-frequency (60 Hz) NMES over the quadriceps
muscles. Stimulation intensity was increased throughout the protocol to achieve a
submaximal target torque output. Mean torque, peak torque and torque-time
integral (TTI) were measured. The 20 Hz protocol produced a higher mean torque (P
= 0.001) and TTI (P = 0.008) compared to the 60 Hz protocol. The stimulation
intensity required to achieve target torque during NMES was not different between
frequencies (P > 0.0001). When the goal is to optimize torque output during
prolonged submaximal NMES, such as during functional electrical stimulation, low
frequency stimulation may be preferred.
PMID- 29945029
TI - Acceleration of saturated porous media clogging and silicon dissolution due to
low concentrations of Al(III) in the recharge of reclaimed water.
AB - The recharge of reclaimed water is an effective strategy for addressing the
issues of water quality deterioration and groundwater level decline
simultaneously. Residual Al coagulants are normally remained in the recovered
water at low concentrations, and may induce clogging problems during the
recharging process. However, this issue has been ignored in the past. In this
study, we investigated the mechanisms of Al(III)-induced aquifer bio-clogging,
the role of Al(III) in quartz sand media (SiO2) dissolution and re-precipitation
in the series of aquifer columns. We determined that Al(III) resulted in serious
clogging in ~140 h at low concentrations that satisfied the national drinking
water standard of China. The corresponding hydraulic conductivity decreased by
more than ~90% in the bacteria-containing aquifer, which was ~30% greater than
that for the bacteria-free trials. The enhanced Al(III)-related clogging was
caused by modifying quartz sand to form Si-O-Al(OH)n and improving microbes
attachment. Microbes retention kinetic coefficients (k) of the Al recharged
simulated aquifer could increase by 3.0-8.3 times. The Al(III) also enhanced
biomass production and clogging by binding to microbial extracellular polymeric
substances. In turn, the greater amount of biomass accelerated the Si dissolution
and re-precipitation, this may potentially damage the stability of aquifer
structure. The results showed that reclaimed water treated with Al coagulation
should be employed with caution for recharging.
PMID- 29945031
TI - Life cycle environmental and economic implications of small drinking water system
upgrades to reduce disinfection byproducts.
AB - Many of the small drinking water systems in the US that utilize simple filtration
and chlorine disinfection or chlorine disinfection alone are facing disinfection
byproduct (DBP) noncompliance issues, which need immediate upgrades. In this
study, four potential upgrade scenarios, namely the GAC, ozone, UV30, and UV186
scenarios, were designed for a typical small drinking water systems and compared
in terms of embodied energy, carbon footprint, and life cycle cost. These
scenarios are designed to either reduce the amount of DBP precursors using
granular activated carbon filtration (the GAC scenario) or ozonation (the ozone
scenario), or replace the chlorine disinfection with the UV disinfection at
different intensities followed by chloramination (the UV30 and UV186 scenarios).
The UV30 scenario was found to have the lowest embodied energy (417 GJ/year) and
life cycle cost ($0.25 million US dollars), while the GAC scenario has the lowest
carbon footprint (21 Mg CO2e/year). The UV186 scenario consistently presents the
highest environmental and economic impacts. The major contributors of the
economic and environmental impacts of individual scenarios also differ. Energy
and/or material consumptions during the operation phase dominate the
environmental impacts of the four scenarios, while the infrastructure investments
have a noticeable contribution to the economic costs. The results are sensitive
to changes in water quality. An increase of raw water quality, i.e., an increase
in organic precursor content, could potentially result in the ozone scenario
being the least energy intensive scenario, while a decrease of water quality
could greatly reduce the overall competitiveness of the GAC scenario.
PMID- 29945030
TI - Carbon and hydrogen isotope analysis of parathion for characterizing its natural
attenuation by hydrolysis at a contaminated site.
AB - The applicability of compound-specific isotope analysis (CSIA) for assessing in
situ hydrolysis of parathion was investigated in a contaminated aquifer at a
former pesticide wastes landfill site. Stable isotope analysis of parathion
extracted from groundwater taken from different monitoring wells revealed a
maximum enrichment in carbon isotope ratio of +4.90/00 compared to the source of
parathion, providing evidence that in situ hydrolysis took place. Calculations
based on the Rayleigh-equation approach indicated that the natural attenuation of
parathion was up to 8.6% by hydrolysis under neutral and acidic conditions. In
degradation experiments with aerobic and anaerobic parathion-degrading microbes,
no carbon and hydrogen isotope fractionation of parathion were observed. For the
first time, CSIA has been applied for the exclusive assessment of the hydrolysis
of phosphorothioate-containing organophosphorus pesticides at a contaminated
field site.
PMID- 29945032
TI - An efficient multi-objective optimization method for water quality sensor
placement within water distribution systems considering contamination probability
variations.
AB - Water quality security within water distribution systems (WDSs) has been an
important issue due to their inherent vulnerability associated with contamination
intrusion. This motivates intensive studies to identify optimal water quality
sensor placement (WQSP) strategies, aimed to timely/effectively detect
(un)intentional intrusion events. However, these available WQSP optimization
methods have consistently presumed that each WDS node has an equal contamination
probability. While being simple in implementation, this assumption may do not
conform to the fact that the nodal contamination probability may be significantly
regionally varied owing to variations in population density and user properties.
Furthermore, the low computational efficiency is another important factor that
has seriously hampered the practical applications of the currently available WQSP
optimization approaches. To address these two issues, this paper proposes an
efficient multi-objective WQSP optimization method to explicitly account for
contamination probability variations. Four different contamination probability
functions (CPFs) are proposed to represent the potential variations of nodal
contamination probabilities within the WDS. Two real-world WDSs are used to
demonstrate the utility of the proposed method. Results show that WQSP strategies
can be significantly affected by the choice of the CPF. For example, when the
proposed method is applied to the large case study with the CPF accounting for
user properties, the event detection probabilities of the resultant solutions are
approximately 65%, while these values are around 25% for the traditional
approach, and such design solutions are achieved approximately 10,000 times
faster than the traditional method. This paper provides an alternative method to
identify optimal WQSP solutions for the WDS, and also builds knowledge regarding
the impacts of different CPFs on sensor deployments.
PMID- 29945033
TI - Degradation of aqueous 2,4,4'-Trihydroxybenzophenone by persulfate activated with
nitrogen doped carbonaceous materials and the formation of dimer products.
AB - In this work, we systematically investigated the persulfate (PS) activation
potential of a series of nitrogen doped carbonaceous materials for the
degradation of 2,4,4'-trihydroxybenzophenone (2,4,4'-HBP), an additive in
polyvinyl acetate films and personal care products. Nitrogen originating from
urea, NH4NO3, indole and polyaniline was doped into carbonaceous materials,
including hydroxylated multi-walled carbon nanotubes (CNT-OH), large-inner thin
walled carboxylated carbon nanotubes (CNT-COOH) and graphite oxide (GO), to
examine the catalytic effect. The NH4NO3-CNT-OH catalyst, which showed the best
catalytic performance in 2,4,4'-HBP removal, was characterized by SEM, TEM, FT
IR, Raman, BET surface area, XRD and XPS, and pyrrolic nitrogen was found to play
a highly important role in the activation of PS. Under the conditions of [2,4,4'
HBP]0: [PS]0 = 1: 500, T = 25 degrees C, pH0 = 7.0, concentration of catalyst =
100 mg L-1, 43.48 MUM 2,4,4'-HBP was completely removed in 2 h. According to
electron paramagnetic resonance (EPR) spectra and radical quenching experiments,
hydroxyl and sulfate radicals on the surface of the catalyst contributed to the
substrate oxidation. Cleavage of C-C bridge bond, hydroxylation and
polymerization were mainly involved in the oxidation process, leading to the
formation of 10 intermediates (e.g., dimers), as detected by the MS/MS spectra.
To the best of our knowledge, this report is the first to describe the
transformation mechanism of 2,4,4'-HBP in nitrogen doped carbonaceous materials
catalyzed PS system.
PMID- 29945035
TI - Role of endothelial primary cilia as fluid mechanosensors on vascular health.
AB - Primary cilia are microtubule-based organelles that protrude from the cell
surface of many mammalian cell types, including endothelial and epithelial cells,
osteoblasts, and neurons. These antennal-like projections enable cells to detect
extracellular stimuli and elicit responses via intracellular signaling
mechanisms. Primary cilia on endothelial cells lining blood vessels function as
calcium-dependent mechanosensors that sense blood flow. In doing so, they
facilitate the regulation of hemodynamic parameters within the vascular system.
Defects in endothelial primary cilia result in inappropriate blood flow-induced
responses and contribute to the development of vascular dysfunctions, including
atherosclerosis, hypertension, and aneurysms. This review examines the current
understanding of vascular endothelial cilia structure and function and their role
in the vascular system. Future directions for primary cilia research and
treatments for ciliary-based pathologies are discussed.
PMID- 29945034
TI - Motor learning and movement automatization in typically developing children: The
role of instructions with an external or internal focus of attention.
AB - The aim of the current study was to examine the effects of an external focus of
attention (i.e., on the movement outcome) versus an internal focus of attention
(i.e., on the movement itself) on motor learning in typically developing
children. We examined both immediate motor performance (i.e., practice effect,
when focus instructions are given) as well as motor performance after one week
(i.e., learning effect). In addition, we examined if an external and an internal
focus of attention differently affected movement automatization, as measured
using a dual-task paradigm. Finally, we explored whether the effect of
attentional focus instructions on motor learning was influenced by children's
working memory capacity. Participants were 8-12 year old (N = 162) typically
developing children. Participants practiced a new motor task (i.e., 'Slingerball
throwing task'). Results showed that an external focus of attention led to higher
throwing accuracy during practice, but this beneficial effect did not extent to
the retention test one week later. Furthermore, movement automatization did not
differ after external or internal focus of attention instructions, and working
memory capacity did not predict motor learning in children in either of the
instruction conditions. This is the first study to show that the beneficial
effects of an external focus of attention on discrete motor tasks found in
previous studies with a child population seem to be short lived and decline after
a one-week interval.
PMID- 29945036
TI - High-fat feeding induces mobilization of vitamin C in obese prone rats.
AB - In obesity and dyslipidemia, hydrolysis of triacylglycerol (TAG) into non
esterified fatty acids (NEFAs) may contribute to insulin resistance, and
production of oxygenated, bioactive polyunsaturated fatty acids may increase
oxidative stress. Here we show that after six weeks of high-fat feeding of obese
prone rats (Crl:OP(CD), vitamin C was increased both in liver (P < 0.01) and
plasma (P < 0.001), while both TAG (P < 0.01) and NEFA (P < 0.001) were lower
than in low-fat fed control rats. Hepatic vitamin C biosynthesis was similar
between groups, indicating that a new steady state level was established with a
higher vitamin C level adequate for supplying the systemic needs. Glucose and
insulin sensitivity were unaffected at this stage. Eventually, the mobilization
of vitamin C may be seen as a mechanism to protect the host against insulin
resistance.
PMID- 29945037
TI - A pilot study of acute phase proteins as indicators of bovine mastitis caused by
different pathogens.
AB - This study analysed three acute phase proteins in milk from natural cases of
bovine mastitis and compared their profiles across different pathogens causing
the infection. Their ability to differentiate subclinical and clinical mastitis
from normal (uninfected) milk samples was also examined. Samples from various
dairy farms across Scotland submitted to the Veterinary Diagnostic Services unit
of the University of Glasgow were used for this study. They were subjected to
microbiological examination for mastitis pathogens, evaluation of somatic cell
counts and analyses by ELISAs for haptoglobin, C-reactive protein and mammary
associated serum amyloid A3. Each acute phase protein (APP) was compared across
pathogens and form of mastitis. Significant differences (P = 0.000) were observed
for each APP between causative pathogen and form of mastitis. There were
significant correlations between the pathogen and the form of mastitis and the 3
APP showed similar profile for the different pathogen type and forms of mastitis.
It can be concluded that the aetiological pathogen of mastitis to a large extent
influences the clinical form of the disease, this, ultimately being reflected in
the degree and course of secretions of the acute phase proteins; Hp, M-SAA3 and
CRP into milk during mastitis. Variations of which, show correspondent patterns
with related pathogen/form-of-mastitis.
PMID- 29945038
TI - MTOR pathway in focal cortical dysplasia type 2: What do we know?
AB - Focal cortical dysplasia (FCD) is the most commonly encountered developmental
malformation that causes refractory epilepsy. Focal cortical dysplasia type 2 is
one of the most usual neuropathological findings in tissues resected
therapeutically from patients with drug-resistant epilepsy. Unlike other types of
FCD, it is characterized by laminar disorganization and dysplastic neurons, which
compromise the organization of the six histologically known layers in the cortex;
the morphology and/or cell location can also be altered. A comprehensive review
about the pathogenesis of this disease is important because of the necessity to
update the results reported over the past years. Here, we present an updated
review through Pubmed about the mammalian target of rapamycin (MTOR) pathway in
FCD type 2. A wide variety of aspects was covered in 44 articles related to
molecular and cellular biology, including experiments in animal and human models.
The first publications appeared in 2004, but there is still a lack of studies
specifically for one type of FCD. With the advancement of techniques and greater
access to molecular and cellular experiments, such as induced pluripotent stem
cells (iPSCs) and organoids, it is believed that the trend is increasing the
number of publications contributing to the achievement of new discoveries.
PMID- 29945039
TI - Drying kinetics, adsorption isotherms and quality characteristics of vacuum-dried
beef slices with different salt contents.
AB - In this study, the effect of salt content (0, 5, 10, 15 and 20 g/100 g dry basis)
on the drying kinetics, adsorption isotherms, and quality characteristics of beef
slices were investigated. Beef slices were salted and vacuum-dried at 70 degrees
C, until a moisture content of 32% (dry basis). The adsorption isotherms of the
dried beef slices were described at 25 degrees C. The drying time for beef
slices at the salt contents of 0, 5, 10, 15 and 20 g NaCl/100 g d.b. were 212,
207, 194, 160 and 137 min respectively. Modified Henderson and Pabis, and Page
models exhibited a better fit for the drying kinetics of beef slices than the
other drying models tested. The adsorption isotherm of dried beef slices is
typical Type-II, but the addition of salt led to this behavior to change to type
III. The BET model (R2 > 0.98 and %E <= 13.40) for all samples exhibited a good
fit to the experimental data.
PMID- 29945040
TI - Oxidative stability of beef from steers finished exclusively with concentrate,
supplemented, or on legume-grass pasture.
AB - The objective of this study was to evaluate the effects of three finishing
systems based on concentrate and legume-grass pasture on beef. Steers were
finished for 91 days with an exclusively whole corn grain-based (GRAIN) diet,
grazed on legume-grass pasture plus 1.4% of body weight of whole corn grain
supplementation (SUPP), or grazed on legume-grass pasture (PAST) only. Lipid and
myoglobin oxidation, pH, objective color, and alpha-tocopherol concentrations
were evaluated on M. longissimus thoracis steaks. Dietary treatments did not
affect pH and minimally affected protein carbonylation. Steaks from steers fed
GRAIN were less red, showed higher lipid oxidation during retail display, and
higher metmyoglobin formation from day 7 to 13 when compared to PAST. Levels of
alpha-tocopherol were higher in steaks from steers fed diets containing legume
and grass. Inclusion of roughage in finishing diets is essential to maintain
retail color and prevent lipid and myoglobin oxidation.
PMID- 29945041
TI - Inequalities in hip fracture incidence are greatest in the North of England:
regional analysis of the effects of social deprivation on hip fracture incidence
across England.
AB - OBJECTIVES: Hip fracture risk varies by geography and by levels of deprivation.
We examined the effect of local area-level deprivation on hip fracture incidence
across nine regions in England, using 14 years of hospital data, to determine
whether inequalities in hip fracture incidence rates vary across geographic
regions in England. STUDY DESIGN: Sequential annual cross-sectional studies over
14 years. METHODS: We used English Hospital Episodes Statistics (2001/02-2014/15)
to identify hip fractures in adults aged 50+ years and mid-year population
estimates (2001-2014) from the Office for National Statistics. The Index of
Multiple Deprivation was used to measure local area deprivation. We calculated
age-standardised hip fracture incidence rates per 100,000 population, stratified
by gender, geographic region, deprivation quintiles and time-period, using the
2001 English population as the reference population. Using Poisson regression, we
calculated age-adjusted incidence rate ratios (IRRs) for hip fracture, stratified
as above. RESULTS: Over 14 years, we identified 747,369 hospital admissions with
an index hip fracture. Age-standardised hip fracture incidence was highest in the
North East for both men and women. In North England (North East, North West and
Yorkshire and the Humber), hip fracture incidence was relatively higher in more
deprived areas, particularly among men: IRR most vs least deprived quintile 2.06
(95% confidence interval [CI] = 2.00-2.12) in men, 1.62 (95% CI 1.60-1.65) in
women. A relationship, albeit less marked, between deprivation and hip fracture
incidence was observed among men in the Midlands and South, but with no clear
pattern among women. CONCLUSIONS: Regional variation in hip fracture incidence
exists across England, with the greatest absolute burden of incident hip
fractures observed in the North East for both men and women. Across local areas
in North England, absolute and relative inequalities in hip fracture incidence
were greater than in other regions. Our findings highlight the need for improved
fracture prevention programmes that aim to reduce regional and social
inequalities in hip fracture incidence.
PMID- 29945042
TI - Women's preferences for the levonorgestrel intrauterine system versus endometrial
ablation for heavy menstrual bleeding.
AB - OBJECTIVES: Women's preferences for treatment of heavy menstrual bleeding (HMB)
are important in clinical decision-making. Our aim was to investigate whether
women with HMB have a preference for treatment characteristics of the
levonorgestrel intrauterine system (LNG-IUS) or endometrial ablation and to
assess the relative importance of these characteristics. STUDY DESIGN: A discrete
choice experiment was performed in general practices and gynaecology outpatient
clinics in the Netherlands. Women with HMB were asked to choose between
hypothetical profiles containing characteristics of LNG-IUS or endometrial
ablation. Characteristics included procedure performed by gynaecologist or
general practitioner; reversibility of the procedure; probability of
dysmenorrhea; probability of irregular bleeding; additional use of contraception;
need to repeat the procedure after five years; and treatment containing hormones.
Data were analysed using panel mixed logit models. The main outcome measures were
the relative importance of the characteristics and willingness to make trade
offs. RESULTS: 165 women completed the questionnaire; 36 (22%) patients were
recruited from general practices and 129 (78%) patients were recruited from
gynaecology outpatient clinics. The characteristic found most important was
whether a treatment contains hormones. Women preferred a treatment without
hormones, a treatment with the least side effects, and no need for a repeat
procedure or additional contraception. Women completing the questionnaire at the
gynaecology outpatient clinic differed from women in primary care in their
preference for a definitive treatment to be performed by a gynaecologist.
CONCLUSIONS: Whether or not a treatment contains hormones was the most important
characteristic influencing patient treatment choice for HMB. Participants
preferred characteristics that were mostly related to endometrial ablation, but
were willing to trade-off between characteristics.
PMID- 29945043
TI - Modeling and validation of a detailed FE viscoelastic lumbar spine model for
vehicle occupant dummies.
AB - The dummies currently used for predicting vehicle occupant response during
frontal crashes or whole-body vibration provide insufficient information about
spinal loads. Although they aptly approximate upper-body rotations in different
loading scenarios, they overlook spinal loads, which are crucial to injury
assessment. This paper aims to develop a modified dummy finite element (FE) model
with a detailed viscoelastic lumbar spine. This model has been developed and
validated against in-vitro and in-silico data under different loading conditions,
and its predicted ranges of motion (RoM) and intradiscal pressure (IDP) maintain
close correspondence with the in-vitro data. The dominant frequency of the model
was f = 8.92 Hz, which was close to previous results. In the relaxation test, a
force reduction of up to 21% was obtained, showing high agreement in force
relaxation during the in-vitro test. The FE lumbar spine model was placed in the
HYBRID III test dummy and aligned in a seated position based on available MRI
data. Under two impulsive acceleration loadings in flexion and lateral directions
with a peak acceleration of 60 m/s2, flexion responses of the modified and
original dummies were close (RoMs of 29.1 degrees and 29.6 degrees ,
respectively), though not in lateral bending (RoMs of 34.1 degrees and 15.6
degrees , respectively), where the modified dummy was more flexible than the
original. By reconstructing a real frontal crash, it was found that the modified
dummy provided a 10% reduction in the Head Injury Criterion (HIC). Other than the
more realistic behavior of this modified dummy, its capability of approximating
lumbar loads and risk of lumbar spine injuries in vehicle crashes or whole-body
vibration is of great importance.
PMID- 29945044
TI - Influence of aggregation on nanoscale titanium dioxide (nTiO2) deposition to
quartz sand.
AB - Although extensive research has been conducted to investigate nTiO2 aggregation
and deposition, effects of aggregation on concurrent/subsequent deposition of
nTiO2, which has important implications to the fate and transport of nTiO2 in
groundwater, has received only limited attention. The objective of this study was
to investigate how pH, dissolved organic matter (DOM), and valence of background
solution cation influence aggregation and concurrent/subsequent deposition of
nTiO2. Experiments were performed to examine nTiO2 aggregation and deposition
onto quartz sand with co-present illite, kaolinite, and montmorillonite colloids
under various geochemical conditions. Results showed that nTiO2 formed hetero
aggregates (i.e., nTiO2-clay aggregates) at low pH when nTiO2 and clay colloids
carried opposite charges, and the hetero-aggregates may either deposit or remain
suspended depending on their interactions with quartz sand and Fe/Al oxyhydroxide
coatings. Deposition of nTiO2 and/or nTiO2-clay aggregates occurred as a result
of electrostatic attraction, secondary minimum, and potentially Mg2+ bridging.
Humic acid prevented nTiO2 aggregation and deposition under most conditions. In
MgCl2 solutions, however, it facilitated deposition by adsorbing to nTiO2 and
Fe/Al oxyhydroxides, thereby enabling Mg2+ bridging. This study demonstrated the
important and complex roles of pH, DOM, cation valence, and clay colloids in
controlling aggregation and subsequent deposition of nTiO2.
PMID- 29945045
TI - Preliminary investigation of quorum quenching effects on sludge quantity and
quality of activated sludge process.
AB - The Quorum Sensing (QS) system has attracted the interest of researchers as a
cell-cell communication system. In activated sludge processes, the production of
extracellular polymeric substances (EPS), biofilms and floc formation are
regulated by the QS system. Hence, disruption of the QS system, called Quorum
Quenching (QQ), could have a significant effect on the quality and quantity of
excess sludge. In the present research, the quorum quenching bacteria,
Rhodococcus sp. BH4 was used as a quorum quencher and was entrapped in an
alginate structure (QQ beads). Three separate sequential batch reactors (SBR)
were constructed and operated as a control reactor, a Low-QQ reactor (containing
150 QQ beads), and a High-QQ reactor (containing 600 QQ beads). Results indicated
that the presence of QQ beads in the aeration reactor leads to a decrease in EPS
content and mean floc particle size in the both Low-QQ and High-QQ reactors. The
eukaryotic community was changed significantly so that the QS disruption caused
an enhancement in microbial predation. The presence of QQ beads also led to a 16
and a 26% decrease in the Yobs coefficient within the Low-QQ and High-QQ
reactors, respectively. Findings of this research revealed a new application of
the QQ system in the activated sludge process, but additional studies are needed.
PMID- 29945047
TI - Effects of wire-type and mesh-type anode current collectors on performance and
electrochemistry of microbial fuel cells.
AB - Carbon-based material is commonly used for anodes in MFCs, but its low
conductivity often limits anodic performance. Application of corrosion-resistive
current collector to carbon-based anode can be a promising strategy for
increasing the anodic performance. In this study, it was hypothesized increasing
metal current collector improved anodic performance. Two different carbon-felt
anodes with titanium wires (CF-W) or stainless steel mesh (CF-M) as a current
collector were tested in a single chamber MFC. In the short-term tests such as
polarization and impedance tests, CF-M with the larger current collector area
(21.7 cm2) had 33% higher maximum power (2311 mW/m2), 81% lower anodic resistance
(3 Omega), and 92% lower anodic impedance (1.1 Omega). However, in the long-term
tests, CF-W with the smaller current collector area (0.6 cm2) showed higher
performance in power and current generation, COD removal, and CE (51%, 10%, 11%,
and 5% higher, respectively) and produced 41% higher net current in cyclic
voltagramm (20.0 mA vs. 14.2 mA). This result shows that larger current collector
is advantageous in short-term performance and disadvantageous in long-term
performance, because the larger current collector is good for current collection,
but interferes with mass transfer and microbial growth.
PMID- 29945046
TI - Photocatalytic ozonation under visible light for the remediation of water
effluents and its integration with an electro-membrane bioreactor.
AB - Photocatalysis and photocatalytic ozonation under visible light have been applied
for the purification of a complex aqueous matrix such as the grey water of Masdar
City (UAE), by using N-doped brookite-rutile catalysts. Preliminary runs on 4
nitrophenol (4-NP) solutions allowed to test the reaction system in the presence
of a model pollutant and to afford the relevant kinetic parameters of the
process. Subsequently, the remediation of grey water effluent has been evaluated
in terms of the reduction of total organic carbon (TOC) and bacterial counts. The
concentration of the most abundant inorganic ionic species in the effluent has
been also monitored during reaction. Photocatalytic ozonation under visible light
allowed to reduce the TOC content of the grey water by ca. 60% in the optimized
experimental conditions and to reduce the total bacterial count by ca. 97%. The
extent of TOC mineralization reached ca. 80% when the photocatalytic ozonation
occurred downstream to a preliminary electro-membrane bioreactor (eMBR). Coupling
the two processes enhanced the global efficiency. In fact, the eMBR treatment
lowered the turbidity and the organic load of the effluent entering the
photocatalytic ozonation treatment, which in turn enhanced the extent of
purification and disinfection.
PMID- 29945048
TI - Indigenous microorganisms residing in oil sands tailings biodegrade residual
bitumen.
AB - The purpose of this study was to determine the capacity of indigenous microbes in
tailings to degrade bitumen aerobically, and if acetate biostimulation further
improved degradation. Fluid fine tailings, from Base Mine Lake (BML), were used
as microbial inocula, and bitumen in the tailings served as a potential carbon
source during the experiment. The tailings were capped with 0.22 MUm-filtered BML
surface water with or without BML bitumen and acetate addition and incubated for
100 days at 20 degrees C. CO2 production and petroleum hydrocarbon reductions
(50-70% for the biostimulation treatment) in the tailings were observed. DNA was
extracted directly from the tailings, and increased bacterial density was
observed by qPCR targeting the rpoB gene in the biostimulated group. 16 S rRNA
sequencing was used to determine microbial composition profiles in each treatment
group. The microbial communities indigenous to the tailings shifted after the
bitumen was added. Acidovorax, Rhodoferax, Pseudomonas and Pseudoxanthomonas spp.
significantly increased compared to the original microbial community and
demonstrated tolerance to bitumen-based toxicity. The first three genera showed
more potential for biostimulation treatment with acetate and may be important
bitumen/hydrocarbon-degraders in an oil sands end pit lake environment.
PMID- 29945049
TI - Heterogeneous kinetics of methoxyphenols in the OH-initiated reactions under
different experimental conditions.
AB - Methoxyphenols as the potential tracers for wood smoke emissions, are emitted
into the atmosphere in large quantities but their atmospheric chemical behaviors
have not been well characterized. In this work, heterogeneous kinetics of
methoxyphenols in the OH-initiated reactions was investigated using a flow
reactor under different experimental conditions. The average second-order rate
constants (k2) of vanillic acid (VA), coniferyl aldehyde (CA), and syringaldehyde
(SA) were (4.72 +/- 0.51) * 10-12, (10.59 +/- 0.50) * 10-12, (12.25 +/- 0.60) *
10-12 cm3 molecule-1 s-1, respectively, obtained at relative humidity (RH) and
temperature of 40% and 25 degrees C. In addition, the results showed that high
temperature played a positive role in promoting these reactions while high RH had
an inhibiting impact. The k2 values of VA, CA, and SA at 40% RH and different
temperature followed the Arrhenius expressions, i.e., k2 = (2.45 +/- 0.40) * 10
10exp [-(1170.73 +/- 47.35)/T], k2 = (6.40 +/- 0.26) * 10-10exp [-(1516.16 +/-
13.71)/T], and k2 = (1.02 +/- 0.13) * 10-9exp [-(1310.79 +/- 36.75)/T],
respectively. Based on the determined rate constants, the atmospheric lifetimes
of these three methoxyphenols ranged from 0.54 to 2.18 d under different
conditions. The experimental results indicate that OH radicals might play an
important role in controlling the atmospheric lifetimes of methoxyphenols, and
also help to further cognize the chemical behaviors of methoxyphenols in the
atmosphere.
PMID- 29945050
TI - N-halamine-based multilayers on titanium substrates for antibacterial
application.
AB - Bacterial infection is one of the most severe postoperative complications leading
to clinical orthopedic implants failure. To improve the antibacterial property of
titanium (Ti) substrates, a bioactive coating composed of chitosan-1
(hydroxymethyl)- 5,5-dimethylhydantoin (Chi-HDH-Cl) and gelatin (Gel) was
fabricated via layer-by-layer (LBL) assembly technique. The results of Fourier
transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1HNMR) and X
ray photoelectron spectroscopy (XPS) showed that Chi-HHD-Cl conjugate was
successfully synthesized. Scanning electron microscopy (SEM), atomic force
microscope (AFM) and water contact angle measurements were employed to monitor
the morphology, roughness changes and surface wettability of Ti substrates, which
proved the multilayers coating formation. Antibacterial assay against Escherichia
coli (E. coli) and Staphylococcus aureus (S. aureus) revealed that the Gel/Chi
HDH-Cl modified Ti substrates most efficiently inhibited the adhesion and growth
of bacteria. Meanwhile, in vitro cellular tests confirmed that Gel/Chi-HDH-Cl
multilayers had no obvious cytotoxicity to osteoblasts. The study thus provides a
promising method to fabricate antibacterial Ti-based substrates for potential
orthopedic application.
PMID- 29945051
TI - In vitro and in vivo tumor annihilation by near-infrared photothermal effect of a
NiFe2O4/C nanocomposite.
AB - Nanothechnology-mediated photothermal therapy (PTT) is emerging as one of the
inspiring alternative modality of cancer therapy that applies near-infrared
radiation. High favorability of this approach is due to its minimum invasiveness,
safety of non-targeted area, quick recovery, and capable simultaneous imaging. In
this approach, photoabsorbing nanomaterials convert energy of infrared light to
vibrational motion and generate heat. In the present study, a nanocomposite
comprised nickel ferrite and carbon (NiFe2O4/C) was synthesized, characterized
and introduced as a novel photoabsorbing agent in cancer phototherapy. NiFe2O4/C
was characterized by field emission scanning electron microscopy, Fourier
transform infrared spectroscopy, and X-ray diffraction patterns. A diode laser of
808 nm with a power density of 1.0 W cm-2 was selected as the light source to
evaluate the photothermal property of NiFe2O4/C toward cancer repression in C540
(B16/F10) cell line and melanoma bearing tumor model in male balb/c mice.
Temperature enhancement ability of NiFe2O4/C confirmed its photoabsorbing
property. While NiFe2O4/C had a concentration dependent cytotoxicity on C540
(B16/F10) cell line, PTT of NiFe2O4/C activated by laser irradiation showed its
destroying effect on the C540 (B16/F10) cell line. On the other hand,
histological analyses and tumor volume changes were performed for the in vivo PTT
of NiFe2O4/C upon intratumoral injection. The results showed that after 24 h, PTT
of the nanocomposite cured the tumor properly, whereas NiFe2O4/C injection or
laser exposure alone had no treatment effect. Also, 5-day post-treating the
melanoma bearing tumor model indicated that the level of necrosis significantly
increased during this time in the PTT treated mouse. Therefore, PTT using
NiFe2O4/C is proposed as a promising procedure for the melanoma cancer therapy.
PMID- 29945052
TI - Antimicrobial potency of differently coated 10 and 50 nm silver nanoparticles
against clinically relevant bacteria Escherichia coli and Staphylococcus aureus.
AB - Silver nanoparticles (nanoAg) are effective antimicrobials and promising
alternatives to traditional antibiotics. This study aimed at evaluating potency
of different nanoAg against healthcare infections associated bacteria: Gram
negative Escherichia coli and Gram-positive Staphylococcus aureus. A library of
differently coated nanoAg of two different sizes (10 and 50 nm) were prepared
using coating agents poly-L-Lysine (PLL), cetyltrimethyl-ammonium bromide (CTAB),
citrate (CIT), polyvinyl-pyrrolidone (PVP), polysorbate 80 (Tween 80), and
dioctyl-sodium sulfosuccinate (AOT). Stability evaluation by means of
agglomeration and dissolution behaviour was performed for all nanoAg under
conditions relevant for this study. Antibacterial properties of nanoAg were
addressed by determining their minimal bactericidal concentrations (MBC) in
deionised (DI) water to minimise the influence of silver speciation on its
bioavailability. In parallel, AgNO3 was analysed as an ionic control. Studied
nanoAg were efficient antimicrobials being remarkably more potent towards E. coli
than to S. aureus (4 h MBC values for different nanoAg ranged from 0.08 to 5.0 mg
Ag/L and 1.0-10 mg Ag/L, respectively). The toxicity of all nanoAg to S. aureus
(but not to E. coli) increased with exposure time (4 h vs 24 h). 10 nm sized
nanoAg released more Ag-ions and were more toxic than 50 nm nanoAg. Coating
dependent toxicity was more prominent for 50 nm nanoAg coated with Tween 80 or
CTAB rendering the least toxic nanoAg. Obtained results showed that the
antimicrobial effects of nanoAg were driven by shed Ag-ions, depended on target
bacteria, exposure time and were the interplay of NP size, solubility and surface
coating.
PMID- 29945053
TI - Assessment of semen quality and fertility in young growing beef bulls exposed to
ergot alkaloids.
AB - The objective of this study was to evaluate semen quality and fertility in beef
bulls grazing the ergot alkaloid (EA) producing tall fescue cultivar, Kentucky 31
(KY31), compared to a novel endophyte (NE) cultivar lacking EA. Two studies were
conducted over a 3-year period. In studies 1 (n = 10; ages >= 24 mo) and 2 (n =
53 over two years; ages 12-16 mo), Angus (AN) bulls were stratified by body
weight (BW), body condition score (BCS), and scrotal circumference (SC), and then
allotted to graze either KY31 or NE for 56 days. Semen samples were collected,
and BW, BCS, and SC were evaluated at the start of treatment (TRT) on day (d) 0
and every 28 days to the end of each study. In addition, blood samples were
collected on d 0 and every 28 days for assessment of circulating prolactin (PRL)
levels in study 2. On d 56, for both studies, semen from bulls (n = 2 per
treatment in study 1 and n = 4 per treatment in study 2) with similar and
acceptable quality were extended, kept at 19 degrees C, and used for timed
artificial insemination (TAI) of primi- and multiparous AN and AN- crossbred
females. Pregnancy was evaluated at 35 and 90 days post-TAI via transrectal
ultrasonography to determine pregnancy rates. Serum PRL concentrations showed a
TRT by d effect (P <= 0.05), with values for bulls grazing KY31 decreased on d 28
and d 56 of grazing compared to NE. In studies 1 and 2, bull BW and BCS were
affected by d (P <= 0.05), but not by TRT. No TRT or TRT by d effect on semen
quality was observed in either study; however, d impacted both velocity and
concentration in study 2 (P <= 0.05). In study 1, TAI pregnancy rates at 35 days
post-TAI were lower (P <= 0.05) in the group inseminated with semen from bulls
grazing KY31; however, in study 2, pregnancy rates did not differ due to
treatment 35 post-TAI (P > 0.05). Grazing KY31 negatively impacted serum PRL
concentrations, supporting previous observations; however, consumption of KY31
had no effect on growth or semen quality of AN bulls ranging from 12 to >=24 mo
of age. Furthermore, fertility data is inconsistent between studies and requires
further investigation.
PMID- 29945054
TI - Molecular characterization and expression analysis of strbp in Chinese tongue
sole (Cynoglossus semilaevis).
AB - Spermatid perinuclear RNA-binding protein (Strbp) is a kind of double-stranded
(ds) RNA specific binding protein that plays important roles in mammalian
spermatogenesis. In this study, we have isolated and characterized the strbp gene
of Chinese tongue sole, Cynoglossus semilaevis, termed as CS-strbp. The CS-strbp
genomic sequence contained fifteen exons and fourteen introns. Its cDNA was 2655
bp in length, encoding a 666-amino-acid protein with two conserved ds binding
motifs. Using quantitative PCR, we found that CS-strbp mRNA exhibited sex-biased
and tissue-specific distribution, predominantly expressed in the fertile male
testis, though the expression levels varied throughout different developmental
stages. Comparison of methylation profile in different sexual genotypes
demonstrated the low methylation level of CS-strbp promoter in male and pseudo
male, which is consistent with the high expression levels in those genotypes. In
situ hybridization revealed that CS-strbp mRNA mainly localized in male germ
cells, especially in spermatids and spermatozoa. Given these findings, we
postulate that CS-strbp might function in spermatogenesis of Chinese tongue sole.
PMID- 29945055
TI - Ultrasound strain imaging in assessment of false vocal folds in adults: A
feasibility study.
AB - PURPOSE: The aim of the study is to investigate the feasibility of ultrasound
strain imaging (USI) in assessing magnitude and symmetry of false vocal folds
(FVF) deformation as a quantitative marker for estimating FVF movement. METHODS:
From October 2016 to July 2017, we performed USI of FVF in 44 adults [33 healthy
controls and 11 subjects with unilateral vocal fold motion impairment (VFMI), 17
men and 27 women, mean age 43 years]. Real time ultrasound data of FVF in
different configuration (abduction and adduction) was acquired through
transcutaneous anterior-mid neck. Peak to valley strain (strain magnitude of
maximum to minimum) representing the largest FVF deformation was estimated using
2-D speckle tracking. We developed peak to valley strain index [(Peak to valley
strain right - Peak to valley strain left)/Peak to valley strain maximum] to
assess the symmetry of FVF deformation. RESULTS: The difference in peak to valley
strain between left and right FVF was significant in subjects with VFMI, whereas
it was not in healthy controls. The peak to valley strain index was small
(<=0.25) in symmetric FVF deformation in healthy controls whereas it was large
(>=0.53) in asymmetric FVF deformation in subjects with VFMI. The area under
receiver operating characteristics for peak to valley strain index in the
determining asymmetric FVF deformation was 1. CONCLUSION: Our results suggest
that USI seems feasible to quantify both magnitude and symmetry of FVF
deformation in adults. Further validation of USI in assessing VFMI is warranted.
PMID- 29945056
TI - Multimodality images of myofibroblastoma in the male breast: A case report and a
review of the literature.
AB - We report a case of a 58-year-old male diagnosed with myofibroblastoma using
mammography, ultrasound, computed tomography (CT) and magnetic resonance imaging
(MRI), as well as present a review of the literature. The pathological diagnosis
was myofibroblastoma with spindle cell neoplasm with immunoreactivity.
Myofibroblastoma is a rare benign disease and there is a lack of reports of
multimodality imaging of this disease. We review the imaging features of this
rare disease across multiple imaging modalities with pathological correlation,
and provide current treatment recommendations as well.
PMID- 29945057
TI - Evaluation of association between degree of background parenchymal enhancement on
MRI and breast cancer subtype.
AB - PURPOSE: Evaluate possible association between BPE and breast cancer tumor
type/prognostic markers. METHODS: IRB approved retrospective study from 1/2010
1/2014 identified 328 patients who had breast MRI and available
clinical/pathology data. BPE was categorized according to BI-RADS. The
association between BPE and breast cancer molecular subtype/prognostic factors
was evaluated. RESULTS: No significant association was present between high BPE
and the following: HER2+ tumors, basal tumors, tumors with axillary nodal
disease, high nuclear grade tumors, high Ki-67 index tumors or larger tumors.
CONCLUSION: Patients with high BPE may be at increased risk for breast cancer but
not necessarily for those cancer subtypes with a poor prognosis.
PMID- 29945058
TI - On-line electrochemistry/electrospray ionization mass spectrometry (EC-ESI-MS)
system for the study of nucleosides and nucleotides oxidation products.
AB - The main aim of present investigation was to study the oxidation products of
nucleosides and nucleotides with the use of on-line electrochemistry/electrospray
ionization mass spectrometry (EC-ESI-MS) system. The conditions applied in the
system were optimized in complex manner, involving study of the impact of working
electrodes or sample solvent on the oxidation of tested compounds and their
ionization in mass spectrometry. Finally 5 mM of ammonium acetate was used
selected and pH 3 was used for positive ionization mode, while pH 7 was applied
for negative ionization in mass spectrometry. It was shown that utilization of
both ionization modes is indispensable in order to detect and identify all of
oxidation products. Furthermore the identification of compounds obtained using
the EC-ESI-MS system was done and results were compared with known metabolites of
studied compounds. These products are associated with specific disease states, or
may be a potential metabolites. Moreover the analysis of urine samples by liquid
chromatography coupled with mass spectrometry confirmed the possibility of using
EC-ESI-MS technique to simulate the metabolism of nucleosides and nucleotides,
since the oxidation products have also been identified in urine samples.
PMID- 29945059
TI - Isolation, identification and in silico toxicity predictions of two isomers from
cefotiam hydrochloride.
AB - Two structural isomers of cefotiam in cefotiam hydrochloride for injection were
observed, and the structures of the isomers were determined by mass spectrometry
and various 1D and 2D NMR techniques. The thermo-isomerization mechanism of
cefotiam was also discussed. Thermo-isomerization occurred not only in cefotiam
but also in cephalosporins containing a 1-alkyl-1H-tetrazole-5-thiol side chain
at C-3. Furthermore, the toxic effects of the two impurities of cefotiam
hydrochloride were predicted and it is thought that they could be more toxic than
cefotiam. The results reported in this article may be important for quality
control and stability studies of this class of drugs.
PMID- 29945060
TI - Development of a simple, rapid and high-throughput fluorescence polarization
immunoassay for glycocholic acid in human urine.
AB - In this paper, a simple, rapid and high-throughput fluorescence polarization
immunoassay (FPIA) based on polyclonal antibodies (PAb) is described for the
determination of glycocholic acid (GCA) in human urine. Three fluorescein-labeled
GCA (tracers) with different structures and spacer bridges were synthesized and
purified by thin-layer chromatography (TLC). The structure effect of tracers on
the assay was investigated and the sensitivity of best tracer in the optimized
FPIA demonstrated an IC50 value of 306 ng/mL. The working range of FPIA was 36 ~
2 600 ng/mL and the limit of detection (LOD) was 9 ng/mL. The developed FPIA was
time-saving that could be completed within 10 min. Human urine samples spiked
with GCA were analyzed by this method, followed by confirmation with commercial
enzyme immunoassay analysis (EIA). Excellent recoveries and correlation between
these two methods were observed (R2 = 0.996), suggesting the developed FPIA could
be applied to screening of GCA in human urine samples without complicated
cleanup.
PMID- 29945061
TI - Exploiting layerwise convexity of rectifier networks with sign constrained
weights.
AB - By introducing sign constraints on the weights, this paper proposes sign
constrained rectifier networks (SCRNs), whose training can be solved efficiently
by the well known majorization-minimization (MM) algorithms. We prove that the
proposed two-hidden-layer SCRNs, which exhibit negative weights in the second
hidden layer and negative weights in the output layer, are capable of separating
any number of disjoint pattern sets. Furthermore, the proposed two-hidden-layer
SCRNs can decompose the patterns of each class into several clusters so that each
cluster is convexly separable from all the patterns from the other classes. This
provides a means to learn the pattern structures and analyse the discriminant
factors between different classes of patterns. Experimental results are provided
to show the benefits of sign constraints in improving classification performance
and the efficiency of the proposed MM algorithm.
PMID- 29945062
TI - Nonparallel support vector regression model and its SMO-type solver.
AB - Although the twin support vector regression (TSVR) method has been widely studied
and various variants are successfully developed, the structural risk minimization
(SRM) principle and model's sparseness are not given sufficient consideration. In
this paper, a novel nonparallel support vector regression (NPSVR) is proposed in
spirit of nonparallel support vector machine (NPSVM), which outperforms existing
twin support vector regression (TSVR) methods in the following terms: (1) For
each primal problem, a regularized term is added by rigidly following the SRM
principle so that the kernel trick can be applied directly to the dual problems
for the nonlinear case without considering an extra kernel-generated surface; (2)
An epsilon-insensitive loss function is adopted to remain inherent sparseness as
the standard support vector regression (SVR); (3) The dual problems have the same
formulation with that of the standard SVR, so computing inverse matrix is well
avoided and a sequential minimization optimization (SMO)-type solver is
exclusively designed to accelerate the training for large-scale datasets; (4) The
primal problems can approximately degenerate to those of the existing TSVRs if
corresponding parameters are appropriately chosen. Numerical experiments on
diverse datasets have verified the effectiveness of our proposed NPSVR in
sparseness, generalization ability and scalability.
PMID- 29945063
TI - Identifying small pelvic inclusions through SEM technology.
AB - Tiny calcified structures may be occasionally recovered during excavation of
human skeletal remains. Since taphonomic processes may displace these structures
from their topographical relation with neighbouring organs or bones, differential
diagnoses may pose a major challenge to the archeologist and/or anthropologist.
Enteroliths, kidney stones or gallstones, phleboliths, calcified ganglia, or
sesamoid bones account for most of such calcified tiny structures. In addition to
their pure medical/paleopathological interest, some remains may be related to
diet, to chronic haemolytic conditions, and/or to infections or chronic
intestinal diseases. We here describe the technical procedures carried out to
confirm or refute the identification of a sesamoid bone. The object in question
was a small (5 * 3 * 2 mm) calcified structure that appeared over the right coxal
bone of an 18th century individual buried in the church Nuestra Senora de La
Concepcion, in Santa Cruz de Tenerife (Canary Islands). For comparative purposes
we also analyzed kidney stones and gallstones from modern individuals. As shown
in this study, scanning electron microscope (SEM) analysis is the preferred
method to establish a precise differential diagnosis in these cases.
PMID- 29945064
TI - Poly(2-oxazoline)s based biomaterials: A comprehensive and critical update.
AB - Poly(2-oxazoline)s have been investigated for decades as biomaterials. Pioneering
early work suggested that hydrophilic poly(2-oxazoline)s are comparable to
poly(ethylene glycol) regarding their potential as biomaterials, but the ready
commercial availability of the latter has led to its meteoric rise to become the
gold standard of hydrophilic synthetic biomaterials. In contrast, poly(2
oxazoline)s almost fell into oblivion. However, in the last decade, this family
of polymers has gained much more interest in general and as biomaterials in
particular. The rich chemistry and comparably straightforward synthesis of poly(2
oxazoline)s gives many opportunities for tailoring the properties of the
resulting biomaterials, allowing the chemist to explore new conjugation
chemistry, and to fine-tune the molar mass, hydrophilic-lipophilic balance as
well as architecture. Thus, the wide range of demands for various applications of
biomaterials can be suitably addressed. This review aims to give a comprehensive
and critical update of the development of poly(2-oxazoline) based biomaterials,
focusing on the last 5 years, which have seen an explosive increase of interest.
We believe that the research regarding this diverse family of polymers will
remain strong and will keep growing, in particular after the promising first-in
human studies of a poly(2-oxazoline) drug conjugate. This review aims at
researchers and students new to this polymer family and seasoned poly(2
oxazoline) experts alike and attempts to showcase how the chemical diversity of
poly(2-oxazoline)s allows a relatively facile and broad access to biomaterials of
all kinds.
PMID- 29945065
TI - Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers
induce chondrogenesis by blocking NF-kappa B signaling pathway.
AB - Cartilage cannot self-repair and thus regeneration is a promising approach to its
repair. Here we developed new electrospun nanofibers, made of poly (epsilon
caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I from calf
skin (termed PC), to trigger the chondrogenic differentiation of mesenchymal stem
cells (MSCs) and the cartilage regeneration in vivo. We found that the PC
nanofibers had a modulus (4.3 Mpa) lower than the PCL-PTHF urethane nanofibers
without collagen I from calf skin (termed P) (6.8 Mpa) although both values are
within the range of the modulus of natural cartilage (1-10 MPa). Both P and PC
nanofibers did not show obvious difference in the morphology and size.
Surprisingly, in the absence of the additional chondrogenesis inducers, the
softer PC nanofibers could induce the chondrogenic differentiation in vitro and
cartilage regeneration in vivo more efficiently than the stiffer P nanofibers.
Using mRNA-sequence analysis, we found that the PC nanofibers outperformed P
nanofibers in inducing chondrogenesis by specifically blocking the NF-kappa B
signaling pathway to suppress inflammation. Our work shows that the PC nanofibers
can serve as building blocks of new scaffolds for cartilage regeneration and
provides new insights on the effect of the mechanical properties of the
nanofibers on the cartilage regeneration.
PMID- 29945066
TI - Feasibility of the electrolarynx for enabling communication in the chronically
critically ill: The EECCHO study.
AB - PURPOSE: To assess feasibility of producing intelligible and comprehensible
speech with an electrolarynx; measure anxiety, communication ease, and
satisfaction before/after electrolarynx training; and identify
barriers/facilitators. METHODS: We included tracheostomized adults from 3 units
following commands, reading English, and mouthing words. On enrolment, we
measured anxiety, ease, and satisfaction with communication. We gave
electrolarynx instruction for <=5 days then 2 independent raters assessed
intelligibility, sentence comprehensibility (9-point difficulty scale), and
Electrolarynx Effectiveness Score (EES), and re-evaluated anxiety, communication
ease, and satisfaction. Interviews explored barriers/facilitators. MEASUREMENTS
AND MAIN RESULTS: We recruited 24 participants (Jan2015-Dec2016). Mean (SD)
intelligibility was 45%(18%) words correct: 57%(21%) when facing. Mean
comprehension difficulty was 6.4(2.0) overall, indicating moderate difficulty
(5.5(2.5) scored visualizing). Mean EES was 2.9(1.0) (3 = improved lip-reading
through recognizable sounds). Anxiety decreased from median 3.8 to 2.0 (P =
.007). Communication was rated easier (median 15 vs 12, P = .04) whereas
satisfaction remained similar (P = .06). Facilitators included device
friendliness, patient independence, and word intelligibility. Barriers were
patient weakness, difficulty positioning the device, and limited sentence as
opposed to word intelligibility. CONCLUSION: The electrolarynx may aid
intelligible speech for some tracheostomized patients if the communication
partner can visualize the users face, and reduce anxiety and make patient
perceived communication easier.
PMID- 29945067
TI - Echocardiographic left ventricular diastolic dysfunction predicts hospital
mortality after out-of-hospital cardiac arrest.
AB - PURPOSE: To determine whether systolic or diastolic dysfunction on transthoracic
echocardiogram (TTE) predicts mortality after out-of-hospital cardiac arrest
(OHCA). METHODS: Retrospective cohort study of 173 OHCA subjects undergoing
targeted temperature management who underwent TTE during hospitalization.
Univariate analysis and multivariate logistic regression were used to determine
associations between TTE measurements of systolic and diastolic function and
systemic hemodynamics with all-cause mortality. RESULTS: Mean age was 61.6 +/-
12.4 years (72.7% male) and initial rhythm was shockable in 89%. Hospital
mortality was 30.6%. Mean LVEF was 40% and was not different in hospital
survivors (p = 0.81). TTE parameters reflecting systolic function and systemic
hemodynamics did not predict hospital mortality. Medial mitral E/e' ratio was
associated with hospital mortality, with an optimal cut-off > 13 (p = 0.002).
After multivariate adjustment, medial mitral E/e' ratio remained predictive of
hospital mortality (OR 1.11, 95% CI 1.03-1.20, p = 0.004). Subjects with a medial
mitral E/e' ratio > 13 had higher mortality during long-term follow-up (p < 0.001
by log-rank). CONCLUSIONS: Diastolic dysfunction (higher medial mitral E/e'
ratio) on TTE independently predicted mortality after OHCA; systolic dysfunction
and TTE hemodynamic parameters did not. This reflects a novel use of Doppler TTE
to predict outcomes after OHCA.
PMID- 29945068
TI - Unexpected local anesthesia toxicity during the ultrasonography-guided peripheral
nerve block.
PMID- 29945069
TI - Acyl-carnitine, C5DC, and C26 as potential biomarkers for diagnosis of autism
spectrum disorder in children.
AB - Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that
shown a close association with impaired lipid metabolism. The acyl-carnitine
spectrum status in Chinese children with ASD has not been reported. In this
study, we assessed the levels of blood acyl-carnitines in Chinese children with
ASD and examined the relation between acyl-carnitine profiles and the
intelligence levels. Blood levels of acyl-carnitines were determined by tandem
mass spectrometry in 60 children with ASD and 30 typically developing children.
Chinese Wechsler Young Children Scale of Intelligence (C-WYCSI) was used in ASD
group. Blood levels of free carnitine, glutaricyl carnitine, octyl carnitine,
twenty four carbonyl carnitine and carnosyl carnitine in the ASD group were
significantly lower than those in the control group. Glutaryl carnitine and
carnosyl carnitine might be potential biomarkers for diagnosis of ASD. The
changes in the acyl-carnitine spectrum indicate potential mitochondrial
dysfunction and abnormal fatty acid metabolism in preschool ASD children.
PMID- 29945071
TI - Odd and disorganized-Comparing the factor structure of the three major schizotypy
inventories.
AB - Schizotypy is a personality-framework currently considered a comprehensive and
useful construct in schizophrenia research and becoming ever more accepted within
psychiatry. Thus, it is crucial to obtain a unifying and generally accepted means
of its measuring. The three most commonly used psychometric schizotypy
inventories, the Wisconsin Schizotypy Scales, Schizotypal Personality
Questionnaire and Oxford-Liverpool Inventory of Feelings and Experiences were,
however, built upon different theoretical schizotypy models, wherefore comparing
results from studies that have used different inventories is difficult and
sometimes questionable. Therefore, an analysis of all three inventories was
conducted within the same sample of 327 healthy participants to illustrate the
similarities and differences in factor structures. Results showed that findings
are likely dependent on the used assessment instrument. A following item-level
factor analysis was conducted to investigate the shared structure of all three
inventories, in order to illustrate a framework interpretable as "common ground"
between measures. This adjusted four-factor structure may be used to better aid
comparisons between schizotypy-studies having used different inventories. At
least, our findings illustrate the necessity of viewing individual results before
the background of the theoretical framework of the respective measurement tool.
PMID- 29945070
TI - The potential protective effects of cannabinoid receptor agonist WIN55,212-2 on
cognitive dysfunction is associated with the suppression of autophagy and
inflammation in an experimental model of vascular dementia.
AB - Vascular dementia (VaD) is characteristic of chronic brain ischemia and
progressive memory decline, which has a high incidence in the elderly. However,
there are no effective treatments for VaD, and the underlying mechanism of its
pathogenesis remains unclear. This study investigated the effects of a synthetic
cannabinoid receptor agonist WIN55,212-2 (WIN) on VaD, and molecular mechanisms
of the effects. VaD model was induced by 2-vessel occlusion (2VO). Spatial
reference learning was evaluated by the Morris water maze, and recognition memory
was assessed using the novel object recognition test. Autophagy-related proteins
[microtubule-associated protein 1 light chain 3 (LC-3) and Beclin-1] were
examined by immunohistochemistry and Western blot. Caspase-3 was detected by
Western blot. Inflammatory factors, tumor necrosis factor alpha (TNF-alpha) and
interleukin 1 beta (IL-1beta), were estimated by reverse transcription-polymerase
chain reaction (RT-PCR) and Western blot. VaD increased the levels of LC-3,
Beclin-1, and inflammatory factors, which were reversed by chronic treatment with
WIN. WIN decreased the expression of Capase-3, and improved the learning and
memory impairment of VaD rats. These data indicate that WIN exerts a
neuroprotective effect on the cognitive deficits of VaD rats, which may be
associated with the suppression of excessive autophagy and inflammation.
PMID- 29945072
TI - Truck attack: Fear of ISIS and reminder of truck attacks in Europe as associated
with psychological distress and PTSD symptoms.
AB - Following an ISIS attack, the present study examined the association between
psychological distress and severe stress symptoms with vulnerability variables:
i.e. Physical proximity to the site of the terror attack, Associative memory of
prior events, Danger perception and ISIS anxiety. Using an online survey, 397
adult participants were recruited, Seventy-two hours after an ISIS terror attack,
and filled out Psychological distress Patient Health Questionnaire 4 and severe
stress symptoms questionnaire as well as physical proximity to the site of the
terror attack, associative memory of prior events, danger perception and ISIS
anxiety scales. Physical proximity to the site of the terror attack and ISIS
anxiety were found to be significantly associated of both psychological distress
and severe stress symptoms. Regarding danger perception, only danger perception
of terror attacks was associated with both psychological distress and with severe
stress symptoms. Lastly, whereas being reminded of the 2014 Jerusalem tractor
attack (tapping to association via location) was neither associated with
psychological distress nor with severe stress symptom, the reminder of the truck
attack in Berlin (tapping into association by recency and similarity) was
associated with psychological distress but not with severe stress symptoms. The
importance of the findings is discussed.
PMID- 29945073
TI - Chilling-induced physiological, anatomical and biochemical responses in the
leaves of Miscanthus * giganteus and maize (Zea mays L.).
AB - Miscanthus * giganteus and Zea mays, closely-related C4 grasses, originated from
warm climates react differently to low temperature. To investigate the response
to cold (12-14 degrees C) in these species, the photosynthetic and anatomical
parameters as well as biochemical properties of the cell wall were studied. The
research was performed using M. giganteus (MG) and two Z. mays lines
differentiated for chilling-sensitivity: chilling-tolerant (Zm-T) and chilling
sensitive (Zm-S). The chilled plants of Zm-S line demonstrated strong inhibition
of net CO2 assimilation and a clear decrease in F'v/F'm, Fv/Fm and phiPSII, while
in MG and Zm-T plants these parameters were almost unchanged. The anatomical
studies revealed that MG plants had thinner leaves, epidermis and mesophyll cell
layer as well as thicker cell walls in the comparison to both maize lines. Cold
led to an increase in leaf thickness and mesophyll cell layer thickness in the Zm
T maize line, while the opposite response was observed in Zm-S. In turn, in
chilled plants of MG and Zm-T lines, some anatomical parameters associated with
bundle sheath cells were higher. In addition, Zm-S line showed the strong
increase in the cell wall thickness at cold for mesophyll and bundle sheath
cells. Chilling-treatment induced the changes in the cell wall biochemistry of
tested species, mainly in the content of glucuronoarabinoxylan, uronic acid, beta
glucan and phenolic compounds. This work presents a new approach in searching of
mechanism(s) of tolerance/sensitivity to low temperature in two thermophilic
plants: Miscanthus and maize.
PMID- 29945074
TI - Host-specific proteomic and growth analysis of maize and tomato seedlings
inoculated with Azospirillum brasilense Sp7.
AB - Azospirillum brasilense Sp7 (Sp7) is a diazotrophic, free-living plant growth
promoting rhizobacterium (PGPR) that is increasingly used for its ability to
reduce stress and improve nutrient uptake by plants. To test the hypothesis that
Sp7 interacts differently with the primary metabolism in C3 and C4 plants,
differential proteomics were employed to study weekly protein expression in Sp7
treated maize (Zea mays cv. B73) and tomato (Solanum lycopersicum cv. Boludo)
seedlings. Plant and root growth parameters were also monitored. Protein changes
were most striking at the four-leaf stage (T1) for both species. Proteins related
to metabolism and redox homeostasis were most abundant in tomato at T1, but
later, plants experienced inhibited Calvin-Benson (CB) cycle and chloroplast
development, indicating that photosynthetic proteins were damaged by reactive
oxygen species (ROS). In maize, Sp7 first increased ROS-scavenging enzymes and
decreased those related to metabolism, which ultimately reduced photoinhibition
at later sampling times. Overall, the early interaction with maize is more
complex and beneficial because the photosynthetic aparatus is protected by the C4
mechanism, thereby improving the interaction of the PGPR with maize. Better
seedling emergence and vigor were observed in inoculated maize compared to
tomato. This study provides an integrated perspective on the Sp7 strain-specific
interactions with young C3 and C4 plants to modulate primary metabolism and
photosynthesis.
PMID- 29945075
TI - Biosynthesis and accumulation of 20-hydroxyecdysone in individual male and female
spinach plants during the reproductive stage.
AB - The steroid 20-hydroxyecdysone (20E) is a major component of phytoecdysteroid in
plants and may play a defensive role against insect pests in higher plants. In
spinach, the biosynthesis and accumulation of 20E have been investigated during
the vegetative stage; however, these processes have not been clearly studied
during the reproductive stage, particularly in male and female individuals. In
this study, we analyzed the level and distribution of 20E in individual male and
female spinach plants during the reproductive stage via high performance liquid
chromatography (HPLC). We found that 20E biosynthesis and accumulation were
markedly different between male and female spinach during the late flowering
stage. Compared with the male plant, biosynthesis of 20E in the leaves was more
active and its accumulation in the floral parts was higher in female plants
during the late flowering stage. These results indicate that the female
reproductive organs at least in PE-positive plants could be effectively protected
against harmful insects via active biosynthesis and accumulation of PE during the
late flowering stage to protect floral parts from harmful insects for seed
formation and store the available 20E in seeds for the next generation.
PMID- 29945076
TI - Double trouble: Nonsuicidal self-injury and its relationship to suicidal ideation
and number of past suicide attempts in clinical adolescents.
AB - BACKGROUND: Death by suicide is one of the leading causes of mortality among
adolescents, and nonsuicidal self-injury (NSSI) is one of the strongest
predictors of suicide attempts (SAs). The underlying bases for this relationship
are unknown. We derived two hypotheses from the Interpersonal Psychological
Theory of Suicide (IPTS): unmet interpersonal needs would explain NSSI's
association with suicidal ideation (SI) and increased capability for suicide
would explain NSSI's relationship with SA. METHODS: Adolescents hospitalized on a
psychiatric inpatient unit (N = 289) provided measures of current SI, number of
past SAs, unmet interpersonal needs (perceived burdensomeness and thwarted
belongingness), capability for suicide (fearlessness about death [FAD] and pain
tolerance), depressive symptoms, and number of NSSI methods utilized. RESULTS:
Depressive symptoms, but not unmet interpersonal needs, explained NSSI's
association with SI. FAD and SI, but not depressive symptoms or pain tolerance,
accounted for NSSI's relationship with SA. FAD was associated with SA, but it did
not fully account for NSSI's relationship with SA. LIMITATIONS: This study
utilized a cross-sectional design and retrospective, self-report measures.
CONCLUSIONS: Our study provides partial support for the role of the IPTS
variables in NSSI's relationship with SA in adolescents. The finding that
depressive symptoms and not unmet interpersonal needs explained NSSI's
relationship with SI contradicts the IPTS. However, in those with SI, FAD was
linearly associated with SA, which is consistent with the IPTS. Future studies
are needed to clarify the persistent basis for NSSI's relationship with SA beyond
FAD and SI.
PMID- 29945077
TI - Trauma-informed schools: Child disaster exposure, community violence and somatic
symptoms.
AB - BACKGROUND: Given the increasing prevalence of natural disasters, trauma-informed
school settings should include efficient methods for assessing child health and
mental health in post-disaster environments. To develop such methods, factors
that contribute to children's vulnerability and key signs of distress reactions
after disasters need to be understood. To address these issues, we evaluated pre
disaster community violence exposure as a vulnerability factor for children's
post-disaster reactions and somatic symptoms as a key post-disaster outcome.
METHODS: We evaluated 426 children exposed to Hurricane Katrina at two timepoints
(3-7 months and 13-17 months post-disaster). Structural equation models evaluated
community violence exposure, hurricane exposure, and posttraumatic stress and
somatic symptoms. RESULTS: Community violence exposure was associated with
increased levels of posttraumatic stress symptoms among disaster-impacted youth,
and did not moderate the relationship between disaster exposure and posttraumatic
stress symptoms. Posttraumatic stress symptoms were associated with somatic
symptoms in the short-term recovery period (3-7 months), but not associated with
somatic symptoms during the longer-term recovery period (13-17 months).
LIMITATIONS: This study did not include school-level factors, and somatic
symptoms were based on parent reports. The study did not include parent
functioning information or distinguish between whether somatic symptoms were
medical or functional in nature. CONCLUSIONS: Post-disaster school-based
screeners may need to incorporate questions related to children's past exposure
to community violence and their somatic symptoms to provide trauma-informed care
for children.
PMID- 29945078
TI - Techno-economic assessment of a multi-effect distillation plant installed for the
production of irrigation water in Arica (Chile).
AB - In the context of a regional Chilean project (FIC Taltape project, BIP code
30158422-0), a multi-effect distillation (MED) pilot plant has been built and
installed in a small community in the north of Chile (Taltape, Arica) in order to
supply treated water for agricultural and domestic purposes. The aim of this
paper is to assess the techno-economic feasibility of this system for supplying
water with the required quality to the population. The characterization of the
feed water and the effluents from the MED pilot plant (distillate and brine),
obtained during five months of operation, has been firstly performed. Then, the
prediction of the operation of the water treatment system with solar energy has
been carried out using a typical meteorological year and the design of a static
solar field that cover the thermal energy needs of the water treatment plant. The
annual simulations of the MED pilot plant operating with solar energy showed that
the water needs can be mostly covered using a static solar thermal field with a
total area of 113.2 m2, which would generate roughly 46% of the total heat
required by the water treatment plant. The technical analysis has been completed
with an exhaustive economic assessment. The specific water costs have been
determined for the MED pilot plant and the scale factor when the productivity is
increased up to 5000 m3/day has been evaluated. The cost of distillated water
produced by the MED plant varied from 15.0 USD$/m3 for the 10 m3/day production
capacity to 1.25 USD$/m3 when this variable is increased to 5000 m3/day.
PMID- 29945080
TI - Geo-detection of factors controlling spatial patterns of heavy metals in urban
topsoil using multi-source data.
AB - Heavy metal contamination has become a serious and widespread problem in urban
environment. Understanding its controlling factors is vital for the
identification, prevention, and remediation of pollution sources. This study
aimed to identify the factors controlling heavy metal accumulation in urban
topsoil using the geodetector method and multiple data sources. Environmental
factors including geology, relief (elevation, slope, and aspect), and organism
(land-use and vegetation) were extracted from a geological thematic map, digital
elevation model, and time-series of Landsat images, respectively. Then, the power
of determinant (q) was calculated using geodetector to measure the affinity
between the environmental factors and arsenic (As) and lead (Pb). Geology was the
dominant factor for As distribution in the this study area; it explained 38% of
the spatial variation in As, and nonlinear enhancements were observed for the
interactions between geology and elevation (q = 0.50) and slope (q = 0.49). Land
use and vegetation bi-enhanced each other and explained 39% of the spatial
variation in Pb. These results indicated that geology and relief were the factors
controlling the spatial distribution of As, and organism factors, especially
anthropogenic activities, were the factors controlling the spatial distribution
of Pb in the study area. As was derived from weathering transportation, and
deposition processes of original bedrock and subsequent pedogenesis, and
anthropogenic activity was the most likely source of Pb contamination in urban
topsoil in Shenzhen. Moreover, geodetector provided evidence to explore the
factors controlling spatial patterns of heavy metals in soils.
PMID- 29945079
TI - Assessment of river sediment toxicity: Combining empirical zebrafish
embryotoxicity testing with in silico toxicity characterization.
AB - Quantitative chemical analyses of 428 organic contaminants (OCs) indicated the
presence of 313 OCs in the sediment extracts from Sava River, Croatia.
Pharmaceuticals were present in higher concentrations than pesticides thus
confirming their increasing threat to freshwater ecosystems. Toxicity evaluation
of the sediment extracts from four locations (Jesenice, Rugvica, Galdovo and
Lukavec) using zebrafish embryotoxicity test (ZET) accompanied with semi
quantitative histopathological analyses exhibited correlation with cumulative
number and concentrations of OCs at the investigated sites (10.05, 15.22, 1.25,
and 9.13 MUg/g respectively). Toxicity of sediment extracts and sediment was
predicted using toxic unit (TU) approach and persistence, bioaccumulation and
toxicity (PBT) ranking. Additionally, influential OCs and genes were identified
by graph mining of the prior knowledge informed, site-specific chemical-gene
interaction models. Predicted toxicity of sediment extracts (TUext) was similar
to the results obtained by ZET and associated histopathology with Rugvica
sediment being the most toxic, followed by Jesenice, Lukavec and Galdovo.
Sediment TU (TUsed) favoured OCs with low octanol-water partition coefficients
like herbicide glyphosate and antibiotics ciprofloxacin and sulfamethazine thus
indicating locations containing higher concentrations of these OCs (Galdovo and
Rugvica) as the most toxic. Results suggest that comprehensive in silico sediment
toxicity predictions advocate providing equal attention to organic contaminants
with either very low or very high log Kow.
PMID- 29945081
TI - U.S. nationwide reconnaissance of ten infrequently monitored antibiotics in
municipal biosolids.
AB - Ten infrequently monitored antibiotics in biosolids were examined in archived
American sewage sludges (n = 79) collected as part of the 2006/2007 U.S.
Environmental Protection Agency (EPA) Targeted National Sewage Sludge Survey.
This study inspected the occurrence of amoxicillin, ampicillin, erythromycin,
furazolidone [proxy metabolite: 3-(2-nitrobenzylidenamino)-2-oxazolidinone (NP
AOZ)], nalidixic acid, oxolinic acid, oxytetracycline, spiramycin, sulfadimidine,
and sulfadimethoxine in sewage sludges after nearly a decade in frozen storage.
Six antibiotics were detected at the following average concentrations (ng/g dry
weight): amoxicillin (1.0), nalidixic acid (19.1), oxolinic acid (2.7),
erythromycin (0.6), oxytetracycline (4.5), and ampicillin (14.8). The remaining
four were not detected in any samples ( 0.90) were observed between the AR and pXRF contents of Ca,
Cu, Cr, Ni, Pb and Zn in the site A, and of Cd, Cu, Pb and Zn in the site B. For
the majority of metals, lower AR than pXRF contents were measured, as result of
the AR incomplete dissolution of metal-bearing silicates. This was not observed
when metals - of anthropogenic origin - occurred in soil in very high
concentrations (i.e., Cr for A and Pb for B). In both sites, the comparison among
different regression parameters revealed a strong metal-dependence. Moreover, for
most of the metals, the parameters of each metal-regression line significantly
differed between the two case studies, indicating site-dependence of regression
fits.
PMID- 29945087
TI - Quantification of the relationship between multiple metal(loid) distribution and
integrated effect of internal-external factors in riverbed sediments across
Xijiang River basin, South China.
AB - Understanding the integrated effect of external factors (e.g., human activities)
and internal factors (e.g., hydrodynamics, sediment properties) on metal(loid)
distributions is necessary for relevant decision-makers to develop river basin
management strategies. In attempts to understand the possible causes of the
distribution of nine target metal(loid)s in riverbed sediments across Xijiang
River basin in China, we grouped and portrayed the multiple metal(loid)
distributions by calculating metal(loid)'s normalised-and-weighted average
concentrations, and then canonical correlation analysis combined with a series of
statistical operations, collectively called optimized CCA analysis, was applied
to quantify the strength of relationship between multiple metal(loid)
distribution and integrated effect of internal-external factors. Results showed
that the target metal(loid)s can be divided into three groups according to their
distribution patterns: Group A (including Zn, As, Cd, Sb and Pb), Group B
(including Cr, Ni and Cu) and Group C (including Tl). Among them, metal(loid)s in
Group A was significantly enriched in comparison with the reference values of
Chinese sediments, and the wide-ranging accumulation of Cd and Sb in the whole
study area needs paying great attention to. For those metals in natural states
(e.g., metals in Group B), the affinity of sediment (e.g., Fe and Mn oxides) is
responsible for their distributions. By contrast, when metal(loid)s (e.g.,
metal(loid)s in Group A and Group C) had obvious anthropogenic sources, the
interferences of anthropogenic inputs (e.g., non-ferrous metal enterprises' waste
discharging activities) and the specific sedimentary characteristics (e.g. karst
topography and low-energy hydrodynamic depositional conditions) in study area can
weaken the correlation between the binding affinity of sediment and the contents
of metal(loid)s. The optimized CCA analysis can be an alternative and
advantageous statistical operation for determining the main types of causes of
multiple metal(loid) distribution in the case of observations with relatively low
case-per-variable ratios.
PMID- 29945088
TI - Responses of microbial carbon metabolism and function diversity induced by
complex fungal enzymes in lignocellulosic waste composting.
AB - Composting is an economic and effective technology for solid waste treatment,
which is an essential method to promote the biogeochemical cycle of contaminants.
However, the application of this technology was limited by the bio-degradative
recalcitrance of lignin and other kind of phytotoxic substances release. The
combination with microorganisms and enzymes is a popular and efficient way to
enhanced composting. This study, referring to metabolic mechanisms, fungal
molecular and biogeochemical cycles, was performed to investigate the effects of
lignin degradation, carbon metabolic diversity, as well as the related changes
induced by these two kinds of complex enzymes in composting. The biological
diversity is important indicator in ecosystem, which concerns the environmental
applicability of one technology. The carbon metabolism diversity reflected the
biogeochemical cycles of organic matter, which was also an essential input to
analyze the effects of composting. The changes on the diversity characteristics
of carbon are essential to comprehensively understand the deep mechanisms of this
process, and extended the application of complex enzymes in the field of enhanced
composting. The analysis of Biolog revealed that the utilization of pyruvic acid
methyl ester, alpha-Cyclodextrin, d-Mannitol, d-Galacturonic, Itaconic acid and l
asparagine were deeply promoted, and that of d, l-alpha-Glycerol-phosphate, l
Threonine, Glycyl-l-Glutamic acid and putrescine were depressed by adding the
complex enzyme in composting. Moreover, according to the data, the addition of
complex enzymes improved the degradation efficiency and the metabolic capacity of
carbon in composting. These findings undoubtedly contribute to the development of
enzyme-based technologies and the applications of complex enzymes in composting,
which is of great benefit to eliminate the limitation and extend the application
of composting.
PMID- 29945089
TI - Identifying localized and scale-specific multivariate controls of soil organic
matter variations using multiple wavelet coherence.
AB - Environmental factors have shown localized and scale-dependent controls over soil
organic matter (SOM) distribution in the landscape. Previous studies have
explored the relationships between SOM and individual controlling factors;
however, few studies have indicated the combined control from multiple
environmental factors. In this study, we compared the localized and scale
dependent univariate and multivariate controls of SOM along two long transects
(northeast, NE transect and north, N transect) from China. Bivariate wavelet
coherence (BWC) between SOM and individual factors and multiple wavelet coherence
(MWC) between SOM and factor combinations were calculated. Average wavelet
coherence (AWC) and percent area of significant coherence (PASC) were used to
assess the relative dominance of individual and a combination of factors to
explain SOM variations at different scales and locations. The results showed that
(in BWC analysis) mean annual temperature (MAT) with the largest AWC (0.39) and
PASC (16.23%) was the dominant factor in explaining SOM variations along the NE
transect. The topographic wetness index (TWI) was the dominant factor (AWC = 0.39
and PASC = 20.80%) along the N transect. MWC identified the combination of Slope,
net primary production (NPP) and mean annual precipitation (MAP) as the most
important combination in explaining SOM variations along the NE transect with a
significant increase in AWC and PASC at different scales and locations (e.g. AWC
= 0.91 and PASC = 58.03% at all scales). The combination of TWI, NPP and
normalized difference vegetation index (NDVI) was the most influential along the
N transect (AWC = 0.83 and PASC = 32.68% at all scales). The results indicated
that the combined controls of environmental factors on SOM variations at
different scales and locations in a large area can be identified by MWC. This is
promising for a better understanding of the multivariate controls in SOM
variations at larger spatial scales and may improve the capability of digital
soil mapping.
PMID- 29945090
TI - Developmental toxicity of synthetic phenolic antioxidants to the early life stage
of zebrafish.
AB - Synthetic phenolic antioxidants (SPAs) have gained high concerns due to their
extensive usages and unintended environmental release via various routes. Their
contamination in water system could pose potential threat to aquatic organisms,
therefore, the studies on the aquatic toxicology of this kind of chemicals are of
high importance. In this research, the developmental toxicities of four commonly
used SPAs, including butylated hydroxyanisole (BHA), butylated hydroxytoluene
(BHT), tert-butyl hydroquinone (TBHQ), and 2,2'-methylenebis (6-tert-butyl-4
methylphenol) (AO2246) were investigated using the zebrafish embryo toxicity test
(ZFET). The results showed that these four SPAs exerted different acute
toxicities to zebrafish, and the toxic order, based on their 96 h LC50 values,
was AO2246 > TBHQ > BHA > BHT, and decreased hatching rates were induced for the
embryos in BHA, TBHQ and AO2246 exposure groups. Non-lethal exposures of BHA
(<=20 MUM), TBHQ (<=20 MUM), BHT (<=200 MUM) and AO2246 (<=2 MUM) decreased the
heart rates and body lengths of zebrafish in exposure concentration-dependent
manners. Diverse morphological deformities, including uninflated swim bladder,
pericardial edema, spinal curvature, severe yolk deformation, or abnormal
pigmentation, were induced in zebrafish larvae upon SPA treatments. The
transcriptional levels of the related genes, examined by quantitative PCR,
indicated that the interferences of SPAs with hypothalamic-pituitary-thyroid axis
(HPT axis), GH/PRL synthesis and Hedgehog (hh) pathway contributed to their
developmental toxicities in zebrafish. The up-regulation of pluripotency
biomarker, Oct4, caused the developmental retardation during the early stages of
zebrafish embryos in BHA and TBHQ exposure groups. The results obtained herein
provided important information on the developmental toxicity of SPAs, which could
be very helpful in guiding the risk assessment on their aquatic toxicology.
PMID- 29945091
TI - Distinct biogeographic patterns of rhizobia and non-rhizobial endophytes
associated with soybean nodules across China.
AB - Both rhizobia and non-rhizobial endophytes (NRE) are inhabitants of legume
nodules. The biogeography of rhizobia has been well investigated, but little is
known about the spatial distribution and community assemblage of NRE. By using
high-throughput sequencing, we compared biogeographic patterns of rhizobial and
non-rhizobial subcommunities and investigated their bacterial co-occurrence
patterns in nodules collected from 50 soybean fields across China. Dispersal
probability was lower in NRE than in rhizobia, as revealed by a significant
distance-decay relationship found in NRE, but not in rhizobia, in addition to a
significant occupancy-abundance relationship in the entire community. Rhizobial
and NRE subcommunities were significantly influenced by different environmental
and spatial variables. Moreover, the rhizobial subcommunities were grouped into
Ensifer- and Bradyrhizobium-dominated clusters that were significantly related to
soil pH. The non-rhizobial subcommunities were grouped into Proteobacteria- and
Firmicutes-dominated clusters that were more influenced by climatic than by
edaphic factors. These results demonstrated that rhizobial and non-rhizobial
subcommunities are characterized by distinct biogeographic patterns. Network
analysis showed rhizobia and NRE as separately grouped and uncorrelated with each
other, suggesting they did not share niche space in soybean nodules. In sum,
these results broaden our knowledge of how bacteria are distributed and assemble
as a community in root nodules.
PMID- 29945092
TI - Epigallocatechin-3-gallate reduces damage to osteoblast-like cells treated with
Zoledronic acid.
AB - OBJECTIVE: analyze the effect of zoledronic acid (ZA) alone and in combination
with epigallocatechin-3-gallate (EGCG) on human osteoblast cells. METHODS: SAOS-2
osteoblastic phenotype cell line treated with different doses (0.01-10 MUM) of ZA
or ZA + EGCG underwent cell viability, mineralization, collagen synthesis and
cell migration tests. RESULTS: Micromolar (1 and 5 MUM) doses of ZA reduced cell
viability (p < 0.001), mineralization (p < 0.001), and collagen synthesis (p <
0.001), while nanomolar doses (0.1 MUM) did not produce any effect. EGCG
application partly reversed the inhibition produced by ZA, and even increased
mineralization (p < 0.001). CONCLUSIONS: the data obtained shows that ZA at
micromolar doses produces negative effects on osteoblast at all parameters
measured, while at nanomolar levels ZA only affected cell migration and had no
other effects on osteoblasts. The addition of EGCG partly reversed the effects
produced by ZA, suggesting that this might be a promising preventative measure
against BRONJ.
PMID- 29945093
TI - Monitoring pipe wall integrity using fiber Bragg grating-based sensing of low
frequency guided ultrasonic waves.
AB - Recent literature shows that low-frequency ultrasonic guided waves experience
mode confinement and loss of axi-symmetry in pipes with axially uniform features
such as eccentricity. Considering extended wall loss as a case of uniform
eccentricity, this paper proposes to monitor pipe integrity by measuring changes
to the modal structure of low-frequency axisymmetric L(0,2) longitudinal guided
waves. Fiber Bragg gratings are shown to be effective in detecting changes to
L(0,2) modal characteristics, providing a novel route to health monitoring of
pipe assets.
PMID- 29945094
TI - Mortality of patients examined at a diagnostic centre: A matched cohort study.
AB - BACKGROUND: 'Diagnostic Centres' has been established to provide a diagnostic
pathway for patients with non-specific, serious symptoms that could be cancer. As
little is known about the prognosis, we aimed to 1) analyse mortality of patients
examined at the diagnostic centre, stratified on diagnostic outcome (cancer,
serious-non-malignant disease, or other/no diagnosis), and 2) compare mortality
for cancer patients examined at the diagnostic centre with cancer patients
diagnosed through other routes. METHOD: Retrospective cohort study including 938
patients examined at the Diagnostic Centre, Silkeborg Regional Hospital, Denmark,
during 2012-2014. Cancer patients examined at the diagnostic centre were matched
(1:10) to a reference group of cancer patients diagnosed through other routes.
Information on diagnosis, death, comorbidity and socioeconomic factors was
obtained by linkage to national Danish registers. Mortality was assessed by
Kaplan Meier mortality survival analysis and hazard ratios of death were
estimated using Cox proportional regression analysis while adjusting for
confounders. RESULTS: The 1-year cumulative mortality was 28% in cancer patients
examined at the diagnostic centre. The hazard ratio of death was seven times
increased in cancer patients compared to patients with other/no diagnosis. The
hazard ratio of death was 0.91 (95% CI: 0.68; 1.22) in cancer patients examined
at the diagnostic centre compared to cancer patients diagnosed through other
routes. DISCUSSION: The mortality among cancer patients examined at the
diagnostic centre was comparable to cancer patients diagnosed through other
routes. The results indicate that cancer patients with non-specific serious
symptoms do not have a worse prognosis than other cancer patients.
PMID- 29945095
TI - Cognition and mobility show a global association in middle- and late-adulthood:
Analyses from the Canadian Longitudinal Study on Aging.
AB - BACKGROUND: Given our aging population, there's great interest in identifying
modifiable risk factors for cognitive decline. Studies have highlighted the
relationship between aspects of mobility and cognitive processes. However,
cognition and mobility are both multifaceted concepts and their
interrelationships remain to be well defined. RESEARCH QUESTION: Here, we firstly
aimed to replicate cross-sectional associations between objective measures of
mobility and cognition. Second, we tested whether these associations remained
after the consideration of multiple age-related confounders. Finally, to test the
hypothesis that the association between mobility and cognition is stronger in
older adults, we examined the moderating effect of age in the association between
mobility and cognition. METHODS: In the Canadian Longitudinal Study on Aging,
28,808 community-dwelling adults (aged 45-87; 51% female) completed mobility
(gait, balance and chair stands) and cognitive (memory, executive function and
processing speed) assessments. General linear models were used to examine
mobility-cognition relationships and the moderating effect of age. RESULTS:
Cognitive measures were significantly associated with mobility measures (all p <
0.001). Further, age significantly moderated the mobility-cognition relationship,
with the strength of the associations generally increasing with age.
SIGNIFICANCE: All cognitive measures were related to indices of mobility,
suggesting a global association. In our moderation analyses, the mobility
cognition relationship often increased with age. However, the small effect sizes
observed suggest that mobility is, in isolation, not a strong correlate of
cognitive performance in middle and late-adulthood.
PMID- 29945096
TI - Walking pattern efficiency during collective load transport.
AB - BACKGROUND: While the locomotor behavior of humans walking alone has been
extensively studied, the locomotor behavior of humans transporting a load
collectively is very poorly documented in the biomechanics literature. Yet,
collective transport could find potential developments in other domains such as
rehabilitation and robotics. RESEARCH QUESTION: If collective load transport is
made economically one could expect that the center of mass of the ensemble formed
by several individuals and the load they carry has the same pendulum-like
behavior as a single individual walking alone. The main objective of our study
was to assess to what extent this is the case. METHODS: We recorded the 3D
kinematics of movement of the body segments of ten dyads formed by two persons
carrying a load together in three successive trials. The individuals carried the
load, side by side, along a 13 m straight trajectory. Then, the recovery rate of
the center of mass of the ensemble formed by the two individuals and the load
they carry (i.e. the rate of transfer between potential and kinetic energy) was
computed. RESULTS: The values of recovery rate were similar to those found in the
literature for individuals walking alone, showing that the external energetic
exchanges occurring during collective transport are as efficient as those
occurring in single gait. The recovery rate also increased in successive trials,
suggesting an improvement of the performance with familiarization. SIGNIFICANCE:
Our results demonstrate the ability of humans to collaborate efficiently for
carrying a load. The values of recovery rate we found could be used as a
benchmark for the control of collaborative robots.
PMID- 29945097
TI - Three-dimensional needs of standardized patients in nursing simulations and
collaboration strategies: A qualitative analysis.
AB - Simulation-based education using standardized patients is recognized as an
effective education method from which students can learn in a safe and controlled
environment, and instructors can provide consistent education. It has been
reported that the level of standardized patients' satisfaction in the simulation
experience positively affects to their case mastery and providing feedback to
learners. This study aimed to explore standardized patients' lived experiences on
nursing simulation using qualitative research to provide empirical resources to
facilitate collaboration with standardized patients for efficacious nursing
simulation. Study participants were recruited from simulation centers and had
experience with nursing simulation education as standardized patients within the
last 3 years. Focus group interviews were conducted to explore experiences of the
12 standardized patients in nursing simulations. The focus group interviews were
conducted with structured four steps of opening, transition, key, and ending
questions, from which additional questions and discussions followed. They were
recorded electronically and transcribed for analysis. Qualitative content
analysis was used to analyze the data. Two researchers read the interview
transcripts several times to become familiar with the content, and then
interpreted them systematically. From the qualitative analysis of standardized
patients' experiences on nursing simulation, 23 codes, 10 sub-categories, 4
categories, and a theme were derived. It would be concluded that standardized
patients have serving, learning, and interpersonal needs on their simulation,
which may be related to their experiences in the simulation that affects learning
outcomes of the students' as well. By facilitating positive experiences of
standardized patients, quality of nursing simulation could be increased to
provide more active and effective learning opportunities for students.
PMID- 29945098
TI - Previous work experience and age do not affect final semester nursing student
self-efficacy in communication skills.
AB - BACKGROUND: With the continuing increase in the older population, being able to
communicate with the elderly is one of the many important skills in caring for
older people. Therefore, student nurses need support during education to be
prepared with the necessary communication skills to meet these demands.
OBJECTIVE: The aim of this study was to describe the development of communication
skills during nursing education. DESIGN: A quantitative descriptive and
comparative study. SETTINGS: The nursing programme at a university in an urban
area of Sweden. PARTICIPANTS: Student nurses in the first and third year in a
nursing programme in Sweden in 2015. METHODS: Data were collected with a self
efficacy questionnaire and analysed with descriptive and comparative statistics.
RESULTS: The student nurses in the final semester had a higher self-rated ability
to communicate with older people than students in the second semester of the
education year. There was also a difference in self efficacy between students
with or without former experience of health care work or work in care with older
persons in the second semester. However, these differences were not seen in the
final semester. The age of the students did not affect the self-efficacy rate in
either semester. CONCLUSIONS: Student nurses in the present study scored
themselves relatively highly, while student nurses in previous studies expressed
a need for more communication skills training. Further studies with observations
of student nurses' actual communicative skills in clinical and simulations
settings are needed, to pinpoint weak spots and targets for such an education.
PMID- 29945099
TI - "The power of Twitter": Using social media at a conference with nursing students.
AB - The potential impact of social media use in nursing education, continuing
professional development, and nurses' advocacy is unfolding at a rapid pace.
Nurse educators are uniquely placed to incorporate the use of social media to
enhance students' learning experiences and support students to develop competency
in the use of social media for patient benefit. This paper outlines a novel way
in which professional education on social media use was integrated into an
undergraduate nursing programme. Digital professionalism was cultivated together
with collaborative active learning. Students connected using the Twitter hashtag
#kclciat18 registered for the 'Connecting it all Together 2017' conference held
at the Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care,
King's College London. Students were invited to participate in an education
session on social media, and live activities using Twitter. The conference
provided students with a forum to learn about Twitter and practice using Twitter
in a professional capacity. Utilising the healthcare conference hashtag
repository, Symplur, quantitative and qualitative measures were accessible
indicating the reach and extent of connectivity. A combination of qualitative and
quantitative outcome measures will help student nurses appreciate the power of
Twitter for patient benefit.
PMID- 29945100
TI - Dihydropyrimidinone/1,2,3-triazole hybrid molecules: Synthesis and anti-varicella
zoster virus (VZV) evaluation.
AB - By combining the structural features of dihydropyrimidinone and 1,2,3-triazole
heterocycles, novel hybrid compounds were synthesized using a simple and
convenient method. A series of novel mono and bis 1,2,3-triazole was synthesized
via copper-catalyzed Huisgen azide-alkyne cycloadditions (CuAAC) under microwave
irradiation. The newly synthesized compounds were evaluated for their antiviral
activity against varicella-zoster virus (VZV). Compounds 6aa, 7ab, 6ba and 6da
showed valuable antiviral activities, with EC50 values ranging from 3.6 to 11.3
MUM against TK+ and TK- VZV and without measurable cell-growth inhibition.
PMID- 29945101
TI - The "Chico Mendes" extractive reserve and land governance in the Amazon: Some
lessons from the two last decades.
AB - The discussions about sustainable development in the Amazon region, in particular
the rubber tree social movement against deforestation and the struggle for land
ownership, culminated in the implementation of conservation units for direct use,
with the main reference being the "Chico Mendes" Extractive Reserve, located in
Xapuri-Acre-Brazil, representing some kind of agrarian reform in the forest. The
objective of the present work is to evaluate some of the lessons learned in the
last two decades related to the guarantee of land ownership and the social
reproduction of extractivists. The ASPF methodology of research project from the
Federal University of Acre was used, based on social indicators such as
schooling, access to land and housing time; economic indicators, such as economic
efficiency and living standards in monetary terms; and environmental indicators
such as land use and deforestation. The results indicate that housing turnover
has decreased significantly in the analyzed period. However, for more than half
of extractivists there is still no guarantee of land ownership. From the economic
point of view, there was a significant reduction in both economic efficiency and
the level of living among families. From the environmental point of view, there
was a slight decrease in forests, with increased deforestation and increased
pasture for cattle production. It is recommended that new research on poverty and
rural development be undertaken to understand the reality of this community.
PMID- 29945102
TI - Energising the WEF nexus to enhance sustainable development at local level.
AB - The water-energy-food (WEF) nexus is increasingly recognised as a conceptual
framework able to support the efficient implementation of the Sustainable
Development Goals (SDGs). Despite growing attention paid to the WEF nexus, the
role that renewable energies can play in addressing trade-offs and realising
synergies has received limited attention. Until now, the focus of WEF nexus
discussions and applications has mainly been on national or global levels, macro
level drivers, material flows and large infrastructure developments. This
overlooks the fact that major nexus challenges are faced at local level. Aiming
to address these knowledge gaps, the authors conduct a systematic analysis of the
linkages between small-scale energy projects in developing countries and the food
and water aspects of development. The analysis is based on empirical data from
continuous process and impact evaluations complemented by secondary data and
relevant literature. The study provides initial insights into how to identify
interconnections and the potential benefits of integrating the nexus pillars into
local level projects in the global south. The study identifies the complex links
which exist between sustainable energy projects and the food and water sectors
and highlights that these needs are currently not systematically integrated into
project design or project evaluation. A more systematic approach, integrating the
water and food pillars into energy planning at local level in the global south,
is recommended to avoid trade-offs and enhance the development outcomes and
impacts of energy projects.
PMID- 29945103
TI - Ecological risk assessment of sedimentary hydrocarbons in a subtropical estuary
as tools to select priority areas for environmental management.
AB - The concentration, distribution, and ecological risk of hydrocarbons, as well as
bulk parameters, were determined in surface sediments of the Babitonga Bay, a
subtropical human-impacted estuary in South Atlantic. Total aliphatic and
polycyclic aromatic hydrocarbons (PAHs) ranged between 0.8 and 201.2 MUg g-1 and
from 8.7 to 5489 ng g-1, respectively. Saguacu Lagoon, the region near the ferry
boat and the vicinity of Sao Francisco harbour (SFH), presented high hydrocarbon
concentrations. Despite the low accumulation trend in this region, the SFH and
city may act as a punctual hydrocarbon source. The inner portion of the estuary
had the finest sediment grains and the highest concentrations of carbon,
nitrogen, and sulphur, indicating its importance as a depositional and cumulative
area. The occurrence of unresolved complex mixture suggested chronic oil
contamination. Petrogenic (based on the high percentage of alkylated PAHs) and
pyrolytic (according to the diagnostic ratios of PAH isomer pairs) sources were
confirmed. Ecological risk assessment was evaluated by the risk quotient (RQ).
All samples had at least one priority PAH present at above the negligible
concentration, including naphthalene, which was observed in all samples. Only the
sites near the ferry boat and at the Saguacu Lagoon contained compounds with
concentrations above their maximum permissible concentrations, while all other
sampling sites are classified as "Low-risk." The spatial distribution of RQs
coincides with PAHs distribution, indicating that the regions near SFH, ferry
boat, and the Saguacu Lagoon should be considered to be priority areas when
making environmental monitoring policies.
PMID- 29945104
TI - Detection of tobacco smoke emanating from human skin surface of smokers employing
passive flux sampler - GCMS system.
AB - Cigarette smoking is a significant risk factor for higher incidences of numerous
adverse health consequences. Related health disorders are also found in non
smokers exposed to secondhand smoke (SHS). To investigate the influence of
cigarette smoking and exposure to SHS on the composition of human skin gas, a
trace biogas emanating from human skin, dermal emissions of volatile compounds
were semi-quantitatively measured for volunteers who smoke a cigarette and those
exposed to SHS. This was performed using a passive flux sampler (PFS) coupled
with gas chromatography mass spectrometry (GCMS). Numerous chemicals were
detected, including acetaldehyde, toluene, 3-methyl furan (3-MF), 2,5-dimethyl
furan (2,5-DMF), 3-ethenyl pyridine (3-EP), and nicotine, in the samples
collected from the smokers after a smoking event, and a remarkable increase in
the amount of chemicals collected was observed just after smoking. These
chemicals were also found in the samples collected from volunteers exposed to
SHS. Assessment of current smoking status is important for managing the negative
effects of active and passive smoking, and for the development of public health
policy. The tobacco specific chemicals such as 3-MF, 2,5-DMF, 3-EP, and nicotine,
emanating from human skin surfaces, represent a potential non-invasive biomarker
for monitoring current smoking status of active and passive smokers after
establishing a more quantitative procedure.
PMID- 29945105
TI - Achievements in robotic automation of solvent extraction and related approaches
for bioanalysis of pharmaceuticals.
AB - Currently, the growing demand on quick, easy and ecological sample pretreatment
methods is unquestionable. Such challenge involves also approaches focusing on
the analysis of pharmaceuticals and other endogenous compounds in biological
matrices, termed as Bioanalysis. Solvent extraction such as liquid-liquid
extraction (LLE), derived liquid phase microextraction (LPME) and related
approaches such as solid liquid extraction (SLE), proved to be applicable in
bioanalysis, as numerous papers have been published in this field. However, their
manual performances may suffer from a long-term and laborious preparation, due to
the inherent complexity of the biological samples. A high sample-throughput
(enabling measurement of tens or hundreds of samples on a daily basis) can be
achieved when automation of sample pretreatment is performed, resulting in
decreased imprecision and low waste production of hazardous solvents and risky
biological materials. Here, robotic systems have a key role, especially when
multiple processing (e.g., 96-well plate format) and coupling to modern
analytical instrumentation (e.g. LC-MS) are combined. A thorough overview on the
up-to-date automations of LLE, LPME, SLE and solid LLE via robotics, is therefore
presented. Pharmaceuticals and related compounds determined in classical liquid
biological samples (i.e. plasma/serum, whole blood, urine, saliva etc.) and
modern dried matrix spots (DMS) were considered as analytes of interest. The
methodologies were critically compared to manual setups and among themselves.
PMID- 29945106
TI - Affinity adsorption of bovine hyaluronidase with ligands targeting to active
site.
AB - Four affinity ligands were designed from 6-chloromethyluracil and 2
aminobenzimidazole and simulated for the interaction with bovine hyaluronidase-1.
Regarding sequence alignment, bovine hyaluronidase-1 precursor showed circa 83.6%
similarity with human hyaluronidase-1. Regarding structural modeling and
molecular docking, bovine hyaluronidase-1 interacted with ligands in the active
site. Using epichlorohydrin, 1,3-propanediamine and cyanuric chloride as spacers,
6-chloromethyluracil and 2-aminobenzimidazole were composed to Sepharose beads.
The modified Sepharose beads were then subjected to adsorption analysis with
bovine hyaluronidase. After one step of affinity adsorption, the samples
extracted from bovine testes were subjected to sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE) analysis and activity assay. As
calculated, the densities of four ligands on sorbents (entitled as L-1, L-2, L-3
and L-4) were 37.7 +/- 2.3, 36.4 +/- 3.2, 42.4 +/- 4.2 and 33.7 +/- 2.3 MUmol/g
wet gel; the theoretical maximum adsorption (Qmax) of bovine hyaluronidase on the
four sorbents were 63.6 +/- 1.6, 72.0 +/- 0.7, 111.0 +/- 4.1 and 121.7 +/- 2.3
mg/g wet gel, respectively; the dissociation constants (Kd) of the four sorbents
were 18.5 +/- 0.8, 48.1 +/- 4.3, 35.0 +/- 3.0, 40.6 +/- 2.7 MUg/g wet gel,
respectively. After optimization, the proteins captured by sorbents attaching 2
aminobenzimidazole based ligands (L-3 and L-4) revealed the main single band at
approximately 50 kDa, and the purities were about 85.2 and 96.4%; the bioactivity
recoveries were 83.5 and 89.4%. In addition, the bands on SDS-PAGE gel were also
extracted and confirmed with linear trap quadropole mass spectrometry (LTQ-MS)
analysis.
PMID- 29945107
TI - New, simple and sensitive HPTLC method for simultaneous determination of anti
hepatitis C sofosbuvir and ledipasvir in rabbit plasma.
AB - Sofosbuvir (SOF) and ledipasvir (LDS) represent anti-hepatitis C binary mixture.
Herein, a fast high-performance thin-layer chromatography (HPTLC) method was
developed, validated and applied for simultaneous determination of SOF and LDS in
biological matrix. An innovative strategy was designed which based on coupling
dual wavelength detection with HPTLC. This strategy enabled sensitive, specific,
high sample throughput and cost-effective determination of the SOF-LDS binary
mixture. The developed HPTLC procedure is based on a simple liquid-liquid
extraction, enrichment of the analytes and subsequent separation with UV
detection. Separations were performed on HPTLC silica gel 60 F254 aluminum plates
with a mobile phase consisting of ethyl acetate-glacial acetic acid (100:5, v/v).
The Rf values for SOF and LDS were 0.62 and 0.30, respectively. Dual wavelength
scanning was carried out in the absorbance mode at 265 and 327 nm for SOF and
LDS, respectively. The linear ranges were 40-640 and 9-144 ng/band for SOF and
LDS, respectively with correlation coefficients of 0.9998. The detection limits
were 10.61 and 2.54 ng/band and the quantitation limits were 32.14 and 7.70
ng/band for SOF and LDS, respectively indicating high sensitivity of the proposed
method. Consequently, this permits in vitro and in vivo application of the
proposed method in rabbit plasma with good percentage recovery (95.68-103.26%).
Validation parameters were assessed according to ICH guidelines. The proposed
method represents a simple, high sample throughput and economic alternative to
the already existing more complicated reported LC-MS/MS techniques. The method
would afford an efficient tool for therapeutic drug monitoring and
bioavailability studies of SOF and LDS.
PMID- 29945108
TI - Ultrasound-assisted emulsification microextraction for rapid determination of
unmetabolized synthetic polycyclic and nitro-aromatic musks in human urine.
AB - An effective method to rapidly determine the presence of seven unmetabolized
synthetic musks in human urine samples is developed. The target musks are five
synthetic polycyclic musks (i.e., celestolide (ADBI), phantolide (AHMI),
traseolide (ATII), galaxolide (HHCB), tonalide (AHTN)), and two nitro-aromatic
musks (i.e., musk xylene (MX) and musk ketone (MK)). The method involved an
ultrasound-assisted emulsification microextraction (USAEME) coupled with gas
chromatography-mass spectrometry (GC-MS). The factors that affect USAEME
efficiency were optimized in detail, and the optimized procedure involved the
rapid injection of 50 MUL of carbon tetrachloride into 1.0 mL of urine sample
(contained 0.1-g of sodium chloride) in a conical bottom glass tube. After 1.0
min ultrasonication and 3 min centrifugation (at 7000 rpm), the sedimented
extract 10 MUL was directly injected into the GC-MS system. The limits of
quantitation (LOQs) varied from 0.1 to 0.5 ng/mL. The precisions for both
repeatability and reproducibility were <8%. The trueness varied from 79 to 96%
with the RSD ranging from 2 to 8%. The total concentrations of the seven
unmetabolized target musks in collected human urine samples were in the range
from 0.93 to 3.74 ng/mL. HHCB and AHTN were detected in all the collected
samples, and the daily excretion doses were evaluated.
PMID- 29945109
TI - A sensitive liquid chromatography-tandem mass spectrometry method for the
quantification of valacyclovir and its metabolite acyclovir in mouse and human
plasma.
AB - It is challenging to conduct a pharmacokinetic (PK) study on mice due to the
limited amount of plasma one can obtain, which is also true for some clinical
studies. Here, we developed and validated a simple, sensitive and robust LC-MS/MS
method for measuring the prodrug valacyclovir (VACV) and its metabolite acyclovir
(ACV) in mouse and human plasma. This assay utilized an acetonitrile protein
precipitation method with isotope-labeled internal standards (IS) and enabled
precise and accurate quantification of VACV and ACV in 10 MUL plasma samples with
a nine-min gradient. The analytes were separated on a Waters Atlantis T3 C18
column. The precursor-product ion transitions for VACV (m/z 325.2 > 152.1), ACV
(m/z 226.2 > 152.1), VACV-D4 (m/z 329.2 > 152.1, IS) and ACV-D4 (m/z 230.2 >
152.1, IS) were detected in a multiple reaction monitoring (MRM) positive ion
mode using an API4000 LC-MS/MS system. The lower limit of quantification (LLOQ)
was 2 nM for both VACV and ACV. The linear range was validated over the
concentration ranges of 2-200 nM and 200-5000 nM for both compounds. The matrix
effect and stability of VACV and ACV were also evaluated. This assay was
successfully applied to a PK study in mice.
PMID- 29945110
TI - Spectrophotometric study on binding of 2-thioxanthone acetic acid with ct-DNA.
AB - Thioxanthone and its derivatives are the most remarkable molecules due to their
vast variety of application such as radiation curing that is, until using them as
a therapeutic drug. Therefore, in this study it was intended to use 2
Thioxanthone acetic acid with and without NaCl in Tris HCl buffer solution
(pH:7.0) to represent the interaction with ct-DNA. The UV-vis absorption spectra
of TXCH2COOH in the presence of ct-DNA showed hypochromism and the intrinstic
binding constant (Kb) was determined as 6 * 103 L mol-1. The fluoresence
intensity of TXCH2COOH with ct-DNA clearly increased up to 101% which indicated
that the fluorescence intensity was very sensitive to ct-DNA concentration. The
binding constant (K) and the values of number of binding sites (n) and were
calculated as 1.8 * 103 L mol-1 and 0.69, respectively. When the quenching
constants (Ksv) of free TXCH2COOH and TXCH2COOH, which were bonded with ct-DNA
were compared, slightly changed values of Ksv were seen. Moreover, displacement
assay with Hoechst 33,258 and viscosity measurements in the presence and absence
of NaCl salt also confirmed the binding mode which noted the electrostatic
interaction following groove binding between TXCH2COOH and ct-DNA. Last but not
least, the salt effect was examined on ct-DNA binding with TXCH2COOH. The results
of the experiments indicated that the groove binding was strengthened by NaCl
whereas in the high NaCl concentration, the binding ability of TXCH2COOH to ct
DNA was inversely affected.
PMID- 29945111
TI - Assessment of physiological responses and growth phases of different microalgae
under environmental changes by Raman spectroscopy with chemometrics.
AB - The assessment for cell physiology and growth phases of microalgae plays
important roles in ecological and environmental fields since it can be used to
forecast water eutrophication level worldwidely. Herein, growth phases and
environmental conditions of microalgae were assessed by combining resonance Raman
mapping spectroscopy with multivariate analysis methods. And, primary Raman
characteristic peaks of microalgae were mined with two-dimensional synchronous
spectra. Thereafter, algal growth phases and environmental conditions of
microalgae were preliminary classified with different tendencies of
characteristic Raman peaks by unsupervised principal component analysis (PCA) and
support vector machine (SVM) methods. Our results demonstrated that resonance
Raman mapping spectroscopy with PCA and SVM classification models can be used to
assess algal growth phases and preliminary predict environmental conditions with
characteristic Raman spectra of microalgae in water bodies.
PMID- 29945113
TI - Label-free fluorescent aptasensor berberine-based strategy for ultrasensitive
detection of Hg2+ ion.
AB - A label-free fluorescent aptasensing platform was fabricated and a simple and
rapid method to detect Hg2+ ion in aqueous solution was put forward by means of
berberine and Hg2+ ion-aptamer are as the fluorescence probe and the recognition
element, respectively. Various factors including the concentration of berberine,
Hg2+ ion and Hg2+ ion-aptamer, pH effect and the reaction time were investigated
in detail. Under the optimal experimental conditions, in the sensing system, the
fluorescence intensity changes displayed a calibration response for Hg2+ ion in
the range of 0.1 MUM to 10.0 MUM and the detection limit was of 7.7 nM (S/N = 3).
The fabricated label-free fluorescence aptasensor is not only conveniently but
also effectively applicable used for analysis of Hg2+ ion in blood serum and tap
water samples and the recovery range is of 96.0%-105.7%. In brief, this study
offers an easy, economical and stable assay system for detecting Hg2+ ion in
rough condition.
PMID- 29945112
TI - A fluorescent probe based on tetrahydro[5]helicene for highly selective
recognition of hydrogen sulfide.
AB - Endogenous hydrogen sulfide plays an important role in various physiological and
pathological processes and the convenient and selective recognition of hydrogen
sulfide has become a research hotspot. We designed and synthesized a
tetrahydro[5]helicene and 2,4-dinitrobenzene conjugate (HD-DNP) as an effective
fluorescent probe for selective detection of H2S. The selective deprotection of
2,4-dinitrophenyl ether group of HD-DNP by H2S led to a dramatic fluorescent
enhancement (101-fold) at 500 nm and colorimetric change in DMSO-PBS solution. HD
DNP displays many advantages including low background without any self
fluorescence, as well as high selectivity towards common bio-thiols such as
Cysteine, Homocysteine and Glutathione. The detection limit of this probe for H2S
was found to be about 2.4 MUM with a wide linear range (10-70 MUM). The response
mechanism of the probe with HS- is confirmed to be thiolysis of the dinitrophenyl
ether induced by HS- through 1H NMR comparison investigations.
PMID- 29945114
TI - Clinical and molecular aspects of breast cancer: Targets and therapies.
AB - Breast Cancer is a complex disease characterized by the occurrence of multiple
molecular alterations. Currently, some molecular markers are in use for breast
cancer diagnostic, prognostic, and predictive purposes. Thus, genetic signatures
are available for improving the decision-making. The biomarkers are also
essential as therapeutic approaches, but many questions remain due to the lack of
efficacy on breast cancer treatment, mainly for triple-negative breast cancer
subtype. Since the genetic profile of breast cancer can also be related to
different ethnic groups and geographic areas, the reference populations of the
genetic assays and clinical trials need to include a broader population beyond
the European and North American patients. In this review, we analyzed the current
and potential molecular markers that could help to improve the strategies for
breast cancer therapy.
PMID- 29945115
TI - The down-regulation of microRNA-137 contributes to the up-regulation of
retinoblastoma cell proliferation and invasion by regulating COX-2/PGE2
signaling.
AB - MicroRNA-137 (miR-137) plays an important role in the development and progression
of many types of human cancers; however, the role of miR-137 in retinoblastoma
(RB) remains unclear. In this study, we aimed to investigate the functional
significance and molecular mechanisms of miR-137 in RB. We reported that miR-137
was frequently down-regulated in RB tissues and cell lines. The overexpression of
miR-137 inhibited RB cell proliferation and invasion, while the suppression of
miR-137 promoted RB cell proliferation and invasion. Bioinformatic analysis
predicted that cyclooxygenase-2 (COX-2) was a potential target gene of miR-137,
which was validated by a dual-luciferase reporter assay. Moreover, our results
showed that miR-137 negatively regulated the expression of COX-2 and the
production of prostaglandin E2 (PGE2) in RB cells. The knockdown of COX-2
suppressed the proliferation and invasion of RB cells as well as the production
of PGE2. The overexpression of COX-2 significantly reversed the inhibitory effect
of miR-137 overexpression on RB cell proliferation and invasion. Taken together,
these results suggest that miR-137 suppresses the proliferation and invasion of
RB cells by targeting COX-2/PGE2. Our study reveals a tumor suppressive role of
miR-137 in the progression of RB and suggests miR-137 as a potentially effective
therapeutic target for the treatment of RB.
PMID- 29945116
TI - Antitumor and immune-modulatory efficacy of dual-treatment based on levamisole
and/or taurine in Ehrlich ascites carcinoma-bearing mice.
AB - Many alternative and complementary therapies for cancer have been reported. The
objective of the present work is to examine antitumor and immune-modulatory
properties of dual-treatment based on levamisole (Lms) and/or taurine (Tau) in
Ehrlich ascites carcinoma-bearing mice. In the current study, Lms (10 mg/kg;
subcutaneously) and Tau (640 mg/kg; intragastrically) was administered alone or
as a dual-treatment. Lms or Tau was administered in combination with
cyclophosphamide (CTX) (100 mg/kg; intraperitoneal) in mice bearing Ehrlich
ascites carcinoma. Treatment with CTX or (Lms plus Tau) significantly reduced the
ascitic tumor cell count, percentage of tumor cell viability while elevated the
tumor inhibition rate and apoptosis percentage compared to non-treated animals.
Dual-treatment (Lms and CTX) or (Tau and CTX) significantly potentiated the
reduction of the ascitic tumor cell count, viability and augmented the tumor
inhibition rate and apoptosis percentage compared to CTX-treated mice. Dual
treatment of (Lms plus Tau), (Lms plus CTX) or (Tau plus CTX) altered splenocytes
immunological profile of CD3+CD4+, CD3+CD8+, CD4+CD25+ and CD11b+Ly6G+ cells in
order to achieve better immune surveillance against tumor cells. In conclusion,
dual-treatments based on Lms and/or Tau are promising therapies for cancer, not
only due to its abilities to induce apoptosis in the tumor cells and modulate the
immune response against them, but also due to its capabilities to potentiate the
chemotherapy anticancer efficacy and minimize its adverse effects.
PMID- 29945117
TI - Signification of protein p-53 isoforms and immune therapeutic success in chronic
lymphocytic leukemia.
AB - In the past few years has used thetechnique for analyzing deletions of genes, its
rearrangements, cross-reactivity or multiplications in human genome affected of
genetic diseases. Was proved that, the best techniques in the investigation of
malignant lymphocytes are the Flow Cytometry, Elisa, ICT and Fluorescence in situ
hybridization (FISH). Last method, FISH is used as an alternative to chromosomal
banding, a conventional application in molecular medicine and can detect the
chromosomal rearrangements and complexes of different genes in malignant
diseases, like chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia,
(ALL), or multiple myeloma (MM). Identification of P53 gene deletions and
mutations in regions of chromosome 17 in hematological malignancies is important
because these mutations have an impact on the clinical management of patients.
PMID- 29945118
TI - A geometric phase analysis method dedicated to nanomaterials orienting along high
index zone axis.
AB - Strain within nanomaterials plays a crucial role in defining their physical and
chemical properties. Geometrical phase analysis (GPA) was widely used to
investigate deformation within nanomaterials. The traditional GPA method using
geometric phases of two lattice fringes provides two-dimensional strain mapping,
which is inapplicable to nanomaterials viewed along high-index zone axis. Herein
using silicon nanoplate embedded in Si0.5Ge0.5 matrix as a test object, we
illustrate a GPA method using single lattice fringes. The availability of this
GPA method was testified by comparison with traditional GPA method. This work
presents an opportunity to extend application of the GPA method.
PMID- 29945119
TI - Three-dimensional scanning transmission electron microscopy of dislocation loops
in tungsten.
AB - Scanning transmission electron microscopy (STEM) imaging using diffraction
contrast is a powerful technique to assess crystal defects. In this work it is
used to assess the spatial distribution of radiation induced defect in tungsten.
In effect, its irradiation leads to the formation of nanometric dislocation loops
that under certain conditions may form intriguing 3-D rafts. In this study, we
have irradiated thin tungsten samples in situ in a TEM with 1.2 MeV W ions to
0.017 dpa at room temperature (RT) and at 700 degrees C. Besides the Burgers
vector analysis, the number density and size of the dislocation loops with their
spatial arrangement were quantitatively characterized by stereo imaging in STEM
mode. Most of the loops have a Burgers vector 1/2 a0 <111>, with some a0 <100> at
room temperature. Loops are located mainly in the simulated damage profile but
there is also a significant portion in deeper regions of the sample, indicating
that loops in W diffuse easily, even at RT. At 700 degrees C, loops form
elongated rafts that contain dislocation segments having a Burgers vector 1/2 a0
<111>. The rafts are narrow and reside on {111} planes; they are elongated along
<110> directions, which correspond, when combined to the rafts' Burgers vector,
to the lines of edge dislocations. Compared to conventional TEM, 3-D analysis in
STEM appears thus as a powerful technique for quantitative analyses of defects in
tungsten, as it allows reducing the background diffraction contrast and reaching
thicker areas of the electron transparent foil, here 0.5 MUm of tungsten at 200
kV.
PMID- 29945120
TI - Inter-laboratory validation study of the ForenSeqTM DNA Signature Prep Kit.
AB - The implementation of massively parallel sequencing (MPS) in forensic science
revealed the advantages of the new method compared to the forensic benchmark in
DNA-STR analysis, the capillary-electrophoresis (CE): Sequence information and
the possibility to multiplex hundreds of markers in one multiplex PCR increase
the discrimination power of a forensic (STR-) profile. The EU funded project
DNASeqEx (DNA-STR Massive Sequencing & International Information Exchange) aims
to evaluate MPS-based materials in their respective developmental stages using
the two established platforms MiSeq FGx (Illumina) and Ion S5TM (Thermo Fisher
Scientific). As part of this project, we present here an inter-laboratory
validation of the ForenseqTM DNA Signature Prep Kit, focussing on STRs included
in primer mix A. Our study comprises tests of concordance, reproducibility,
sensitivity (1 ng, 500 pg, 250 pg, 125 pg, 63 pg, 31 pg) and mixtures (male-male
and male-female at ratios of 1:1, 1:5, 1:10, 1:15, 1:20, 1:100, 1:500, 1:1000).
Sequencing results found to be virtually concordant to CE results, to reference
profiles and reproducible between duplicates and between both laboratories. We
observed first locus drop-outs (LDO) at a DNA input of 63 pg (20 sample pool) and
125 pg (38 sample pool). Alleles were found to be well balanced at a DNA input of
250 pg or more. We found the kit to perform well on moderate mixtures (1:1-1:20).
PMID- 29945121
TI - Effects of incomplete residential histories on studies of environmental exposure
with application to childhood leukaemia and background radiation.
AB - When evaluating environmental exposures, residential exposures are often most
relevant. In most countries, it is impossible to establish full residential
histories. In recent publications, childhood leukaemia and background radiation
have been studied with and without full residential histories. This paper
investigates the consequences of lacking such full data. Data from a nationwide
Finnish Case-Control study of Childhood Leukaemia and gamma rays were analysed.
This included 1093 children diagnosed with leukaemia in Finland in 1990-2011.
Each case was matched by gender and year of birth to three controls. Full
residential histories were available. The dose estimates were based on outdoor
background radiation measurements. The indoor dose rates were obtained with a
dwelling type specific conversion coefficient and the individual time-weighted
mean red bone marrow dose rates were calculated using age-specific indoor
occupancy and the age and gender of the child. Radiation from Chernobyl fallout
was included and a 2-year latency period assumed. The median separation between
successive dwellings was 3.4 km and median difference in red bone marrow dose 2.9
nSv/h. The Pearson correlation between the indoor red bone marrow dose rates of
successive dwellings was 0.62 (95% CI 0.60, 0.64). The odds ratio for a 10 nSv/h
increase in dose rate with full residential histories was 1.01 (95% CI 0.97,
1.05). Similar odds ratios were calculated with dose rates based on only the
first dwelling (1.02, 95% CI 0.99, 1.05) and only the last dwelling (1.00, 95% CI
0.98, 1.03) and for subjects who had lived only in a single dwelling (1.05, 95%
CI 0.98, 1.10). Knowledge of full residential histories would always be the
option of choice. However, due to the strong correlation between exposure
estimates in successive dwellings and the uncertainty about the most relevant
exposure period, estimation of overall exposure level from a single address is
also informative. Error in dose estimation is likely to cause some degree of
classical measurement error resulting in bias towards the null.
PMID- 29945122
TI - Pregnancies Following Hysteroscopic Removal of Retained Products of Conception
after Delivery Versus Abortion.
AB - AIM: To compare clinical variables, sonographic findings and pregnancy outcomes
following the hysteroscopic removal of retained products of conception (RPOC)
after delivery and abortion. METHODS: This is a retrospective cohort of operative
hysteroscopies performed between 2011 and 2015 for suspected RPOC, during which
trophoblastic tissue was obtained. Patient demographics, clinical presentation,
sonographic evaluation, subsequent infertility and pregnancy outcomes were
compared between post-delivery (n = 85) and post-abortion (n = 93) cases.
RESULTS: The main presenting symptom in both study groups was vaginal bleeding.
On sonographic evaluation, maximal endometrial thickness was significantly higher
in the post-delivery group, while irregularity and increased flow were more
common in the post-abortion group. There was a similar rate of deliveries
following hysteroscopy in both groups with 40% in the post-delivery group and
39.7% in the post-abortion group. Deliveries in the post-delivery group were
characterized by a higher rate of abnormal placentation - 30.5% - including low
lying placenta and placenta accreta. A significant rate of vaginal deliveries in
both groups entailed manual removal of the placenta or exploration of the uterine
cavity (23.5 and 10.5%, p = 0.20). CONCLUSION: Pregnancies following RPOC after
delivery entail a higher rate of abnormal placentation.
PMID- 29945123
TI - Intergenerational Effects of Maternal Exposure to Drought in Utero on Newborn
Size in Rural Malawi.
PMID- 29945125
TI - Management of Abdominoperineal Excision of the Rectum in a Patient with Glanzmann
Thrombasthenia.
PMID- 29945124
TI - A Preliminary Study of Central Nervous System Arousal and Sleep Quality in
Bipolar Disorder.
AB - Sleep disturbances are commonly reported in patients with bipolar I disorder
(BPI) and are risk factors for mood episodes. In other populations, central
nervous system (CNS) hyperarousal is associated with sleep initiation and
maintenance problems, and CNS hypoarousal is associated with increased sleep
drive. However, it is unclear whether CNS arousal levels are a useful index of
sleep disruption in BPI. This study aimed to investigate daytime CNS arousal
levels in relation to perceived sleep quality in BPI. Resting EEG, mood state,
and self-reported sleep quality data were collected from 34 individuals with BPI.
CNS hyperarousal was associated with pervasive poor subjective sleep quality
including increased sleep disturbances, increased sleep latency, and reduced
global sleep quality. CNS hypoarousal was associated with greater daytime
sleepiness, indicating reduced arousal. These preliminary findings suggest that
CNS arousal may be a useful index for identifying individuals at high risk for
relapse into a mood episode. A limitation of this study is the use of self-report
instruments for sleep quality assessment. Future research should investigate the
temporal relationship of CNS arousal to sleep disturbances using objective
measurements of sleep quality such as polysomnography. If these findings are
replicated, measures of CNS arousals may allow for identification of high-risk
patients with BPI.
PMID- 29945126
TI - Reduction of Peripapillary Vessel Density by Optical Coherence Tomography
Angiography from the Acute to the Atrophic Stage in Non-Arteritic Anterior
Ischaemic Optic Neuropathy.
AB - PURPOSE: To analyse superficial peripapillary vascularization in non-arteritic
anterior ischaemic optic neuropathy (NAION) at acute and atrophic (3 months)
stage. PROCEDURES: Prospective case-control study including 6 patients with NAION
and 10 age-matched healthy controls evaluated with optical coherence tomography
angiography (OCT-A; Angioplex-Cirrus) at acute and atrophic stage. Apart from the
-commercially provided measurements for vessel density (VD) and perfusion density
(PD), a custom image analysis was used to quantify the peripapillary capillary
density (PCD). RESULTS: NAION-group demonstrated a significant decrease in the
PCD, VD and PD compared with fellow unaffected and control groups at acute and
atrophic stage. At 3 months, the average and the temporal sector in PCD
correlated with logMAR VA (-0.943, p = 0.005 and -0.829, p = 0.042 for average
and temporal sectors respectively) and with MD (0.943, p = 0.005; and 0.899; p =
0.015, respectively). Over 3 months, there was a significant PCD reduction at the
temporal sector and at the inner circle in VD and PD, which correlated with
ganglion cell-inner plexiform layer (GCIPL) thinning over the 3 months period
after the acute NAION (0.749, p = 0.020; 0.885, p = 0.002; 0.767, p = 0.016
respectively). CONCLUSION: Both strategies demonstrated a significant
peripapillary microvascular dropout in NAION, but the customized analysis
detected them -earlier. A progressive vessel reduction occurs within the first 3
months, which correlates with GCIPL thinning.
PMID- 29945127
TI - Endoscopic and Histopathology Characteristics in Patients with Esophageal High
Grade Intraepithelial Neoplasia.
AB - BACKGROUND/AIMS: To correlate the endoscopic characteristics with the
histopathology of specimens of esophageal high-grade intraepithelial neoplasia
obtained by endoscopic submucosal dissection (ESD). METHODS: This was a
retrospective study developed from January 2010 to December 2015. The study
included 169 patients who underwent ESD and were diagnosed with esophageal high
grade intraepithelial neoplasia according to endoscopic forceps biopsy, Lugol
staining, endoscopic ultrasonography, computed tomography, and Narrow-Band
Imaging. The demographic, endoscopic, and histopathologic characteristics were
analyzed. RESULTS: A total of 19 cases (11.2%) had a change in diagnosis after
histopathology exam and 16 (9.5%) needed a change in established treatment. An
increase in the severity of disease was correlated with a lesion size > 2 cm,
less than 4 samples in biopsy, and depressed or excavated patterns (p < 0.05).
One hundred forty patients (82.8%) underwent curative resection. Lesions with
leukoplakia (p < 0.001) and negative Lugol staining (p = 0.028) were independent
risk factor for non-curative resection. CONCLUSION: This study confirms that
lesion size > 2 cm, depressed and excavated patterns, and <=4 biopsy samples are
independent risk factors for histological grade changes compared to pre
endoscopic treatment diagnosis. Similarly, leukoplakia and no Lugol staining of
lesions are independent risk factors for non-curative resection.
PMID- 29945128
TI - Patterns of Erythropoiesis-Stimulating Agent Use in European Hemodialysis
Patients: The Dialysis Outcomes and Practice Patterns Study.
AB - BACKGROUND: Clinicians providing dialysis care have numerous erythropoiesis
stimulating agents (ESAs) available for treating anemia. We sought to provide a
contemporary description of ESA types used in hemodialysis (HD) settings in nine
European countries. METHODS: Our study uses Dialysis Outcomes and Practice
Patterns Study phase 5 (2012-2015) data from nine European countries (Belgium,
France, -Germany, Italy, Russia, Spain, Sweden, Turkey, and the United Kingdom).
A total of 164 facilities and 3,281 patients contributed cross-sectional data.
ESA types captured included short-acting epoetins (e.g., epoetin alfa, beta,
etc., including biosimilars), darbepoetin alfa, and continuous erythropoietin
receptor agonist (CERA; methoxy polyethylene glycol-epoetin beta). RESULTS: We
observed broad variability across countries in prescription of ESA types:
prescription of epoetin alfa or epoetin beta ranged from 22% (France) to 78%
(Russia), darbepoetin alfa prescription ranged from 13% (Russia) to 53% (UK), and
CERA prescription ranged from <3% (Sweden) to 26% (France). Prescription of
different ESA types varied substantially within some European countries from 2012
2015 but not across all countries in aggregate. Number of ESA types prescribed by
a facility varied from 1, 2, 3, or 4 different ESA types in 32, 40, 21, and 8% of
facilities, respectively. No differences were seen in the unadjusted
distributions of achieved hemoglobin values by ESA type. CONCLUSION: A variety of
short- and long-acting ESAs are commonly used in European HD facilities to
maintain hemoglobin at remarkably similar levels with each ESA type. The
availability of numerous ESA options for managing anemia has allowed European
providers to optimize anemia management according to the particular circumstances
of each patient.
PMID- 29945130
TI - Professor Jean-Pierre Relier.
PMID- 29945129
TI - Influence of Chemotherapy on Allergen-Specific IgE.
AB - BACKGROUND: Atopy is defined as excess allergen-specific IgE (A-IgE). IgE is
produced by plasma cells that differentiate from allergen-specific B cells. B
cells are known to be killed by chemotherapy; however, it is not known whether A
IgE-secreting plasma cells are killed or inhibited by chemotherapy. If yes, serum
A-IgE levels would be expected to decrease after chemotherapy. OBJECTIVES: We
aimed to determine whether A-IgE levels in atopic individuals (serum A-IgE >=0.35
kUA/L) decrease into the nonatopic range (< 0.35 kUA/L) after chemotherapy.
METHODS: In 105 patients undergoing chemotherapy for acute leukemia, we measured
serum A-IgE before and after chemotherapy. In a subset of these patients, we also
measured B cell counts before and after chemotherapy. RESULTS: Of the 105
patients, 36 were atopic. In these patients, median A-IgE level before
chemotherapy was 1.6 kUA/L whereas the median level after chemotherapy was 0.6
kUA/L (p < 0.001). In 12/36 (33%) patients, A-IgE levels decreased into the
nonatopic range. In nonatopic patients (n = 69), the median A-IgE level also
dropped: from 0.04 kUA/L before to 0.03 kUA/L after chemotherapy (p = 0.001).
Among the total patients (n = 105), the median pre:post-chemotherapy A-IgE ratio
was 1.8 (2.6 in atopic and 1.5 in nonatopic patients). In contrast, the median
ratio of pre:post-chemotherapy B cell counts was 87.6. CONCLUSIONS: A-IgE levels
decrease after chemotherapy but markedly less than B cell counts. Thus, at least
some A-IgE plasma cells appear to survive chemotherapy.
PMID- 29945131
TI - Changes in Hemagglutinin and Neuraminidase Genes of pH1N1 Influenza Virus Strains
Collected from a North Indian Tertiary Care Hospital during 2015.
AB - OBJECTIVE: The study was conducted to analyze changes in HA and NA genes of
pandemic pH1N1 strains, collected from North Indian tertiary care hospital during
2015 and studied the nucleotide change since 2009. Differences in clinical
features of cases positive and negative for influenza viruses were also studied.
METHODS: All samples referred for H1N1 testing, were tested for influenza
viruses. Randomly selected 25 strains of pH1N1 were studied for nucleotide
sequences of HA & NA gene. The nucleotide changes occurring since 2009 were
studied by mutational and phylogenetic analysis. Clinical details of cases were
recorded and analysed. RESULTS: A total of 3319 cases of acute respiratory
infections (ILI/SARI) were tested for influenza viruses during Jan to April 2015,
of which 815 cases tested positive for pH1N1. Nucleotide variation of 2015
strains, from influenza A/California/07/2009 strain at HA1 and NA1 gene was 1.9%
and 3.8% respectively. Both HA1 and NA1 coding sequence showed eight mutations.
Four of HA1(K180Q, S202T, S220T, and A273T) and NA1 (N200S, V241I, N248D, and
N270K) mutations were observed in all pH1N1 study strains. CONCLUSIONS: Strains
of pH1N1 isolated during year 2015 diverged from previously circulating strains.
Their association with severity of illness needs to be further studied.
PMID- 29945132
TI - Effect of Vitamin D Supplementation on Some Inflammatory Biomarkers in Type 2
Diabetes Mellitus Subjects: A Systematic Review and Meta-Analysis of Randomized
Controlled Trials.
AB - BACKGROUND/AIMS: The mechanism, by which vitamin D influences inflammatory
biomarkers in type 2 diabetes mellitus (T2DM), is not very well known. Thus, a
meta-analysis of randomized controlled trials was conducted to assess the effect
of vitamin D supplementation on some inflammatory biomarkers in T2DM subjects.
METHODS: We searched randomized controlled trials from PubMed and the Cochrane
Library in October 2017 and conducted a meta-analysis to evaluate the
effectiveness of vitamin D supplementation on high-sensitivity C-reactive protein
(hs-CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6).
Either a fixed-effects or a random-effects model was used to calculate pooled
effects. RESULTS: We identified 13 studies that met our inclusion criteria. The
results indicated that the vitamin D supplementation significant decreased the hs
CRP level by 0.45 MUg/mL, whereas the vitamin D supplementation did not
influence the TNF-alpha and IL-6. Subgroup analysis showed that vitamin D
significantly lowered hs-CRP by 0.34 MUg/mL among trials with a daily vitamin D
dose <=4,000 IU and by 0.31 MUg/mL among trials with time of vitamin D
supplementation > 12 weeks. CONCLUSIONS: Vitamin D supplementation is beneficial
for the reduction of hs-CRP inT2DM subjects but does not have a significant
influence on TNF-alpha and IL-6 in T2DM subjects.
PMID- 29945134
TI - Myeloid-Derived Suppressor Cells in Infection: A General Overview.
AB - After initial infection, the immune response that serves to restrict the invading
pathogen needs to be tightly calibrated in order to avoid collateral
immunopathological damage. This calibration is performed by specialized
suppressor mechanisms, which are capable of dampening overwhelming or unremitting
inflammation in order to prevent tissue damage. Myeloid-derived suppressor cells
(MDSC) are emerging as key players in counter-balancing inflammatory responses
and pathogenesis during infection. However, some pathogens are able to exploit
the suppressive activities of MDSC to favor pathogen persistence and chronic
infections. In this article, we review the current knowledge about the importance
of MDSC in the context of bacterial, virus, parasites, and fungal infections.
PMID- 29945133
TI - Depersonalization Under Academic Stress: Frequency, Predictors, and Consequences.
AB - BACKGROUND: Based on the assumptions that depersonalization symptoms are relevant
for test anxiety maintenance, we examined their frequency, psychological
predictors, association with anxiety symptoms, and association with test
performance. SAMPLING AND METHODS: In Study 1, 203 students rated their test
anxiety severity and depersonalization in their last oral examination. In Study
2, we assessed test anxiety 1 week before an oral examination, depersonalization,
safety behaviors, self-focused attention, and negative appraisals of
depersonalization directly after the examination, and post-event processing 1
week later among 67 students. RESULTS: In Study 1, 47.3% reported at least one
moderate depersonalization symptom. In Study 2, test anxiety and negative
appraisals of depersonalization significantly predicted depersonalization.
Depersonalization was linked to a higher intensity of safety behaviors and post
event processing but not to self-focused attention. It was not related to
performance. CONCLUSION: Results are limited by the non-random sampling and the
small sample size of Study 2. However, by showing that depersonalization
contributes to the processes the maintenance of test anxiety, the findings
confirm that depersonalization - normally understood as an adaptive mechanism to
cope with stressful events - can become maladaptive.
PMID- 29945135
TI - Gaucher Disease and Myelofibrosis: A Combined Disease or a Misdiagnosis?
AB - BACKGROUND: Gaucher disease (GD) and primary myelofibrosis (PMF) share similar
clinical and laboratory features, such as cytopenia, hepatosplenomegaly, and
marrow fibrosis, often resulting in a misdiagnosis. CASE REPORT: We report here
the case of a young woman with hepatosplenomegaly, leukopenia, and
thrombocytopenia. Based on bone marrow (BM) findings and on liver biopsy showing
extramedullary hematopoiesis, an initial diagnosis of PMF was formulated. The
patient refused stem cell transplantation from an HLA-identical sibling. Low-dose
melphalan was given, without any improvement. Two years later, a BM evaluation
showed Gaucher cells. Low glucocerebrosidase and high chitotriosidase levels were
indicative for GD. Molecular analysis revealed N370S/complex I mutations. Enzyme
replacement therapy with imiglucerase was commenced, resulting in clinical and
hematological improvements. Due to an unexpected and persistent organomegaly, PMF
combined with GD were suspected. JAK2V617F, JAK2 exon 12, MPL, calreticulin, and
exon 9 mutations were negative, and BM examination showed no marrow fibrosis. PMF
was excluded. Twenty years after starting treatment, the peripheral cell count
and liver size were normal, whereas splenomegaly persisted. CONCLUSION: In order
to avoid a misdiagnosis, a diagnostic algorithm for patients with
hepatosplenomegaly combined with cytopenia is suggested.
PMID- 29945137
TI - Genetic Predisposition to Myeloproliferative Neoplasms: Another Piece of the
Puzzle.
PMID- 29945136
TI - Case Series: Pediatric Shunt Tunnel Catheter Infection.
AB - Shunt infections are common pediatric neurosurgical cases with high morbidity
that almost always requires surgical removal of the shunt, external ventricular
drain placement, and delayed shunt replacement. Tunnel infections are well
described clinical entities occurring with indwelling catheters, whereby the
indwelling tunnel portion of a line becomes externally infected with a sterile
central lumen. These infections are typically treated with line replacement or
antibiotics depending on clinical circumstances. We describe 2 cases of shunt
tunnel infection. Both cases presented as erythema over the thoracic portion of
the shunt without signs of CNS infection, with only a remote history of shunt
surgery and no recent systemic illness. One case was treated with a course of
antibiotics, and the other with surgical removal and eventual replacement. Both
children made full recoveries. Our case series juxtaposes 2 alternative
successful strategies for treating the rare entity of shunt tunnel infection.
PMID- 29945138
TI - Cariogenicity of a Milk-Based Drink Used as a Dietary Supplement for Older Adults
Using a Root Caries Experimental Model.
AB - The aim of this study was to evaluate the cariogenicity of a milk-based drink
intended for older adults that was used as part of a governmental initiative in
Chile to improve their nutritional conditions. This drink contains a high
concentration of sugars, which can contribute to root caries development. To test
this hypothesis, an experimental biofilm/caries model was used. Dentin slabs were
used to grow biofilms of Streptococcus mutans UA159. Slabs/biofilms were exposed
3* per day to bovine milk with different fat content, the milk-based drink, and
the milk-based drink supplemented with 10 g of sucrose added per serving. Slabs
exposed to 10% sucrose or 0.9% NaCl were used as positive and negative controls,
respectively. Biofilms were analyzed for bacterial counts and acidogenicity.
Dentin demineralization was estimated by the loss of surface microhardness and
integrated mineral loss. Results were compared by analysis of variance and
Tukey's test. The milk-based drink showed higher acidogenicity than milk with its
entire (whole) or reduced total fat content (skim). The milk-based drink
supplemented with -sucrose had similar acidogenicity as the 10% sucrose positive
control (p = 0.506). Whole milk exposure elicited lower bacterial counts than the
positive control, the milk-based drink, and the milk-based drink supplemented
with sucrose (p = 0.002; 0.006 and 0.014 respectively). Although skim milk
induced higher demineralization than whole milk, both milk types produced lower
demineralization than the milk-based drink. Regarding integrated mineral loss,
demineralization induced by the milk-based drink and the milk-based drink
supplemented with sucrose was similar to that induced by the positive control and
skim milk (p > 0.05). Sugar-containing milk-based drinks used as dietary
supplements for older adults may be highly cariogenic and could represent a
potential risk for root caries.
PMID- 29945139
TI - The Outcome of Complex Hepato-Pancreato-Biliary Surgery for Elderly Patients: A
Propensity Score Matching Analysis.
AB - BACKGROUND/AIMS: Postoperative mortality and morbidity rates after hepato
pancreato-biliary (HPB) surgery remain high, and the number of elderly patients
requiring such surgery has been increasing. This study aimed to investigate
postoperative outcomes of complex HPB surgery for elderly patients. METHODS: We
retrospectively reviewed perioperative data of 721 patients who underwent complex
HPB surgery between 2010 and 2015. The patients were divided into 2 groups:
elderly (>=75 years) and non-elderly (< 75 years). Surgical outcomes of both
groups were compared after propensity score-matching analysis. Subsequently, risk
factors for serious postoperative morbidity were identified by multivariate
analysis. RESULTS: Before matching, the elderly group (n = 170) had more
comorbidities, such as cardiovascular and renal disease, than the non-elderly
group (n = 551). Matching yielded elderly (n = 170) and non-elderly groups (n =
170) with similar preoperative backgrounds. The mortality and morbidity rates did
not differ significantly between the groups. In multivariate analyses, operative
time (OR 1.79; p = 0.005) and blood loss (OR 1.66; p = 0.03) were identified as
independent risk factors for serious postoperative morbidity, whereas older age
did not have a predictive impact (OR 1.16; p = 0.52). CONCLUSIONS: Although
elderly -patients had more comorbidities and higher incidences of postoperative
mortality and several complications before matching, their postoperative outcomes
were equivalent to those of non-elderly patients after matching.
PMID- 29945140
TI - Optimal Timing of Removal of Epidural and Urethral Catheters to Avoid
Postoperative Urinary Retention Undergoing Abdominal Surgery.
AB - BACKGROUND/AIMS: Postoperative urinary retention (POUR) is one of the most
frequent complications of epidural anesthesia. This study aims to clarify risk
factors of POUR and to estimate the appropriate timing of urethral catheter
removal. METHODS: Between September and December 2014, a retrospective cohort
study was conducted on 120 patients who underwent epidural anesthesia and major
abdominal surgery. To observe trends in incidence of POUR, we analyzed the order
and interval of removal of epidural and urethral catheters using Cochran-Armitage
trend test. RESULTS: In this study, 40 patients were diagnosed with POUR (33.3%).
Median removal of epidural catheters was 4 postoperative days in the POUR group
and 3.5 postoperative days in the non-POUR group (p = 0.04). When the urethral
catheter was removed before epidural catheter, incidence of POUR was
comparatively greater (p < 0.001). There were no statistical differences in
surgical fields, operation approach, epidural catheter levels, or epidural opioid
use. No patients had urinary tract infections. CONCLUSION: We demonstrated that
removal of urethral catheter before epidural catheter contributed to increasing
trends in incidence of POUR. The optimal order and interval of removal of
epidural and urethral catheters should be considered to avoid POUR after
abdominal surgery.
PMID- 29945141
TI - Heboidophrenia and Pseudo-Psychopathic Schizophrenia: Current Knowledge and
Critical Perspective.
AB - In this article, based on literature review, we present an integrated description
of heboidophrenia and pseudo-psychopathic schizophrenia. Both diagnostic
constructs describe latent psychotic processes inextricably bound with
psychopathic features. Although both have been described in different eras and
research threads, they are that similar that we could not find divergences. We
formulated operational criteria for clinical and research purpose. The
recognition of this syndrome improves risk management, treatment, and legal
decisions.
PMID- 29945142
TI - An Observational Study Evaluating the Performance of LENT Score in the Selected
Population of Malignant Pleural Effusion from Lung Adenocarcinoma in Singapore.
AB - BACKGROUND: Patients with malignant pleural effusion (MPE) secondary to lung
cancer have been associated with poor prognosis historically. LENT score
developed to risk-stratify unselected patients with MPE predicts prognosis of < 6
months in patients with lung cancer. OBJECTIVE: To assess the performance of LENT
score in predicting prognosis in selected population of MPE secondary to lung
adenocarcinoma alone. METHODS: A retrospective observational study was conducted
by reviewing the medical records of patients managed for MPE in the year 2012.
RESULTS: Seventy patients with lung adenocarcinoma presenting with MPE were
studied. The median (range) LENT score at initial diagnosis was 5 (2-7), and the
median survival 7.9 (0.13-40) months. Thirty-nine patients received epidermal
growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs). The median LENT
score and median survival was 4 (2-7) and 14.4 months, respectively, in this
group. Those in high-risk category by LENT in this group (n = 19) had a median
survival and 6-month survival of 17.4 months and 73.6%, respectively. Thirty-one
patients were treated with conventional chemotherapy. The median LENT score and
median survival was 5 (2-7) and 4.1 (0.13-34.3) months, respectively, in this
group. The median survival and 6-month survival rate in patients in high-risk
category and moderate-risk category by LENT score was 6.2 months and 52.7%, and
11.4 months and 70.5%, respectively. CONCLUSION: LENT score underestimates
prognosis in patients having MPE secondary to lung adenocarcinoma. This disparity
particularly applies to the lung adenocarcinoma patients carrying EGFR mutation.
Hence, LENT score may not be applicable to, or may need modification before
applying to such patients.
PMID- 29945144
TI - Abstracts XVII Conference of SEN and X Meeting of ACCA.
PMID- 29945143
TI - Real-Life Clinical Effectiveness of Razumab(r) (the World's First Biosimilar of
Ranibizumab) in Retinal Vein Occlusion: A Subgroup Analysis of the Pooled
Retrospective RE-ENACT Study.
AB - BACKGROUND: This subgroup analysis of the RE-ENACT study evaluates the
effectiveness of Razumab(r) (the world's first biosimilar of ranibizumab by Intas
Pharmaceuticals Ltd.) in Indian patients with retinal vein occlusion (RVO).
METHODS: The data on patients with RVO who had received >=3 injections of
Razumab(r) between January and August 2016 were analyzed. Endpoints were:
improvement in best corrected visual acuity (BCVA), and a decrease in central
macular thickness (CMT), intraretinal fluid (IRF), and subretinal fluid (SRF)
from baseline at weeks 4, 8, and 12. RESULTS: Of 160 patients, the majority
(61.87%) were men. The mean (+/-SE) BCVA improved from baseline (0.76 +/- 0.04)
to week 4 (0.73 +/- 0.03; p = 0.0656), which attained significance at week 8
(0.55 +/- 0.02; p < 0.0001) and week 12 (0.47 +/- 0.02; p < 0.0001). The mean (+/
SE) CMT significantly decreased from baseline (447.60 +/- 10.91 MUm) to week 4
(431.84 +/- 10.92 MUm; p = 0.0028), week 8 (339.28 +/- 8.12 MUm; p < 0.0001), and
week 12 (298.23 +/- 6.68 MUm; p < 0.0001). The proportion of patients with IRF
and SRF significantly (p < 0.0001) decreased from baseline to weeks 4, 8, and 12
(IRF: from 70.63 to 45.63, 39.38, and 30.00%, respectively; SRF: from 65.63 to
37.50, 28.13, and 24.38%, respectively). A subgroup analysis of branch RVO and
central RVO showed similar results. No new safety concerns were observed.
CONCLUSION: Razumab(r) (biosimilar of ranibizumab) effectively improved visual
acuity and disease outcomes in patients with RVO in a real-world setting with no
new safety concerns.
PMID- 29945145
TI - Prognostic Indicators in Stage IV Surgically Treated Gastric Cancer Patients: A
Retrospective Multi-Institutional Study.
AB - INTRODUCTION: The role of gastric resection in treating metastatic gastric
adenocarcinoma is controversial. In the present study, we reviewed the short- and
long-term outcomes of stage IV patients undergoing surgery. METHODS: A
retrospective review was conducted that assessed patients undergoing elective
surgery for incurable gastric carcinoma. Short- and long-term results were
evaluated. RESULTS: A total of 122 stage IV gastric cancer patients were
assessed. Postoperative mortality was 5.7%, and the overall rate of complications
was 35.2%. The overall survival rate at 1 and 3 years was 58 and 19%
respectively; the median survival was 14 months. Improved survival was observed
for the factors age less than 60 years (p = 0.015), site of metastases (p =
0.022), extended lymph node dissection (p = 0.044), absence of residual disease
after surgery (p = 0.001), and administration of adjuvant chemotherapy (p =
0.016). Multivariate analysis showed that residual disease and adjuvant
chemotherapy were independent prognostic factors. CONCLUSIONS: The results of
this study suggest that surgery combined with systemic chemotherapy in selected
patients with stage IV gastric cancer can improve survival.
PMID- 29945146
TI - Two Randomised Clinical Trials on the Use of Bryophyllum pinnatum in Preterm
Labour: Results after Early Discontinuation.
PMID- 29945147
TI - Tumour Characteristics of Patients with Colorectal Cancer after Acute
Uncomplicated Diverticulitis.
AB - BACKGROUND: The association between diverticulitis and colorectal cancer (CRC)
remains unclear, though both share epidemiological characteristics. The aim of
this study was to investigate whether there is higher risk for CRC after an
episode of uncomplicated diverticulitis. Furthermore, in cases of CRC, we sought
to determine specific tumour characteristics. METHODS: This retrospective
observational study includes patients with acute diverticulitis (Hinchey 0 and 1)
who were conservatively treated with or without antibiotics between 2008 and
2013. Patients with endoscopic follow-up were included for analysis. Tumour
characteristics of patients diagnosed with CRC during colonoscopic follow-up
according to patients' presentation of alarm symptoms were considered to be the
primary endpoint. RESULTS: A total of 977 patients were conservatively treated
for an episode of acute diverticulitis, 645 of whom underwent colonoscopy during
follow-up. Ten patients were diagnosed with CRC, nine of whom exhibited alarm
symptoms. One patient was diagnosed with stage I disease, 4 had stage II, and 5
had stage III disease. CONCLUSIONS: This study strongly suggests that even though
CRC is rare after uncomplicated diverticulitis, in cases of alarm symptoms, a
colonoscopy is indicated. In cases where CRC is diagnosed, it is often advanced
with a higher TNM stage and poor prognosis.
PMID- 29945148
TI - German National Guideline for Treating Chronic Respiratory Failure with Invasive
and Non-Invasive Ventilation: Revised Edition 2017 - Part 1.
AB - Today, invasive and non-invasive home mechanical ventilation have become a well
established treatment option. Consequently, in 2010, the German Respiratory
Society (Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin, DGP) has
leadingly published the Guidelines on "Non-Invasive and Invasive Mechanical
Ventilation for Treatment of Chronic Respiratory Failure." However, continuing
technical evolutions, new scientific insights, and health care developments
require an extensive revision of the Guidelines. For this reason, the updated
Guidelines are now published. Thereby, the existing chapters, namely technical
issues, organizational structures in Germany, qualification criteria, disease
specific recommendations including special features in pediatrics as well as
ethical aspects and palliative care, have been updated according to the current
literature and the health care developments in Germany. New chapters added to the
Guidelines include the topics of home mechanical ventilation in paraplegic
patients and in those with failure of prolonged weaning. In the current
Guidelines, different societies as well as professional and expert associations
have been involved when compared to the 2010 Guidelines. Importantly, disease
specific aspects are now covered by the German Interdisciplinary Society of Home
Mechanical Ventilation (DIGAB). In addition, societies and associations directly
involved in the care of patients receiving home mechanical ventilation have been
included in the current process. Importantly, associations responsible for
decisions on costs in the health care system and patient organizations have now
been involved.
PMID- 29945149
TI - Extra-Pulmonary Neuroendocrine Carcinomas: A Population-Based Study in the
Netherlands.
AB - BACKGROUND: Extra-pulmonary neuroendocrine carcinomas (EP-NEC) are rare tumours
that require expertise for correct and timely diagnosis, which is essential for
clinical decision making. The number of patients affected, treatment given, and
the proportion surviving the disease is based on limited evidence. The aim of
this study is to retrospectively analyse the incidence, treatment, and relative
survival (RS) of EP-NEC patients in the Netherlands. METHODS: Patients diagnosed
between 2008-2012 with EP-NEC or NEC with unknown primary site (UP-NEC) were
selected from the Netherlands Cancer Registry based on combinations of tumour
localisation and morphology code. Incidence was studied using the European
standardised (ESR) and world standardised rates, and RS was calculated using the
Ederer II method. RESULTS: In total, 1,544 cases were analysed, 1,045 EP-NEC and
499 UP-NEC. For EP-NEC, the incidence was 1.0 per 100,000 person-years (ESR), the
mean age was 68 years, and the male to female ratio was 1: 0.6. Most frequent EP
NEC localisations were the bladder and the gastrointestinal tract, and the
treatment most frequently given was surgery in combination with chemotherapy. The
overall 5-year RS was 38% for patients with local/regional disease (n = 447), and
7% for patients with extensive disease (n = 582). For UP-NEC patients (n = 499),
the 5-year RS was 6%. CONCLUSIONS: This study is the first nationwide study
presenting an increase in the incidence of EP-NEC patients from 196 to 260 cases
annually in the Netherlands. The best 5-year RS was found for EP-NEC patients
with local disease located in the bladder, where the worst 5-year RS was found
for patients with disease located in the oesophagus.
PMID- 29945150
TI - Cost-Effectiveness of a Multifaceted Podiatry Intervention for the Prevention of
Falls in Older People: The REducing Falls with Orthoses and a Multifaceted
Podiatry Intervention Trial Findings.
AB - BACKGROUND: Falls are a major cause of morbidity among older people. Multifaceted
interventions may be effective in preventing falls and related fractures.
OBJECTIVE: To evaluate the cost-effectiveness alongside the REducing Falls with
Orthoses and a Multifaceted podiatry intervention (REFORM) trial. METHODS: REFORM
was a pragmatic multicentre cohort randomised controlled trial in England and
Ireland; 1,010 participants (> 65 years) were randomised to receive either a
podiatry intervention (n = 493), including foot and ankle strengthening
exercises, foot orthoses, new footwear if required, and a falls prevention
leaflet, or usual podiatry treatment plus a falls prevention leaflet (n = 517).
PRIMARY OUTCOME: incidence of falls per participant in the 12 months following
randomisation. SECONDARY OUTCOMES: proportion of fallers and quality of life (EQ
5D-3L) which was converted into quality-adjusted life years (QALYs) for each
participant. Differences in mean costs and QALYs at 12 months were used to assess
the cost-effectiveness of the intervention relative to usual care. Cost
effectiveness analyses were conducted in accordance with National Institute for
Health and Clinical Excellence reference case standards, using a regression-based
approach with costs expressed in GBP (2015 price). The base case analysis used an
intention-to-treat approach on the imputed data set using multiple imputation.
RESULTS: There was a small, non-statistically significant reduction in the
incidence rate of falls in the intervention group (adjusted incidence rate ratio
0.88, 95% CI 0.73-1.05, p = 0.16). Participants allocated to the intervention
group accumulated on average marginally higher QALYs than the usual care
participants (mean difference 0.0129, 95% CI -0.0050 to 0.0314). The intervention
costs were on average GBP 252 more per participant compared to the usual care
participants (95% CI GBP -69 to GBP 589). Incremental cost-effectiveness ratios
ranged between GBP 19,494 and GBP 20,593 per QALY gained, below the conventional
National Health Service cost-effectiveness thresholds of GBP 20,000 to GBP 30,000
per additional QALY. The probability that the podiatry intervention is cost
effective at a threshold of GBP 30,000 per QALY gained was 0.65. The results were
robust to sensitivity analyses. CONCLUSION: The benefits of the intervention
justified the moderate cost. The intervention could be a cost-effective option
for falls prevention when compared with usual care in the UK.
PMID- 29945151
TI - Genetic Variability in E6 and E7 Oncogenes from Human Papillomavirus Type 58 in
Mexican Women.
AB - BACKGROUND/AIMS: The study aimed to describe human papillomavirus (HPV) 58
genetic variability in E6 and E7 oncogenes from women in southeast Mexico and
their phylogenetic relationships with the sequences from other geographical
regions. METHODS: The E6-E7 region was amplified by nested PCR, and sequenced for
identification of polymorphisms, phylogenetic trees construction, and haplotype
and fixation tests. RESULTS: HPV58 positive samples were obtained from a
repository, 54 were amplified, 47 sequences for the E6 gene, and 51 sequences for
the E7 gene were obtained. Fifteen new E6 mutations were found; the most frequent
were G279T (G57V; 29.78%), T249G (F47C; 34.04%), and A270G (Y54C; 34.04%), and
previously reported c307t (63.82%). For E7, 17 known mutations were found, the
most frequent were C632T (T20I), 35.30%, G760A (G63S), 35.30%, and t744g 74.50%.
No significant association with the severity of the lesions was found. The
polytomy in the E6 tree did not allow proposing phylogenetic relationship, and E7
tree presented defined branches. All sequences were presumably A lineage, most
closely related to A1 and/or A3 sublineage. HPV58 variants are not specific for a
geographical area. Population and fixation analyses suggest a possible Asian
origin of HPV58 from Yucatan. The most frequent E7 haplotype in Yucatan groups
with other populations of the world. CONCLUSION: The genetic variability of HPV58
from Mexico was described for the first time. E7 was more conserved than E6. New
mutants present exclusively in Yucatan were identified.
PMID- 29945152
TI - What Should a Gynecologist Know about Li-Fraumeni Syndrome? Lessons from a
Patient Undergoing Hysterectomy for Benign Indications.
AB - Li-Fraumeni syndrome (LFS) is a rare highly penetrant cancer syndrome
characterized by mutation in the TP53 tumor suppressor gene. Recent data suggest
that this germline mutation is more frequent than once thought. While LFS has not
been associated previously with pelvic serous carcinoma, gynecologic malignancies
have been reported in this patient population. We present the case report of a 37
year-old patient with known LFS and a history of multiple cancers who underwent
total abdominal hysterectomy for benign indications with incidental bilateral
salpingo-oophorectomy. On final pathology, she was found to have serous tubal
intraepithelial carcinoma of bilateral fallopian tubes. Our findings raise the
question of the potential role of prophylactic gynecologic cancer-reducing
surgery in this patient population.
PMID- 29945153
TI - The Dopamine Receptor D2 C957T Polymorphism Modulates Early Components of Event
Related Potentials in Visual Word Recognition Task.
AB - BACKGROUND: Visual word recognition is one of the central topics in cognitive
psychology and cognitive neuroscience. Genetic factors are known to contribute to
the visual word recognition, but no genes associated with this process have been
identified so far. We studied the impact of the DRD2 C957T polymorphism on the
efficiency of visual word recognition by measuring its neuronal correlates and
behavioral parameters. Early (~200 ms) components of event-related potentials
(ERP) were recorded during a lexical decision task. The DRD2 C957T polymorphism
is thought to be associated with D2 receptor's availability and binding
potential. Earlier studies have demonstrated the influence of this variation on
perception and processing of verbal stimuli. The DRD2 C957T is also associated
with schizophrenia, with the C allele being the risk allele. METHODS:
Electroencephalogram, genetic, and behavioral data were collected from 96 healthy
individuals (53.1% men). ERPs were recorded for words and pseudowords in implicit
and explicit tasks. Two regions of interests in the left ventral temporal cortex,
whose role in early visual word processing is well established, were selected for
analysis. RESULTS: The results showed the main effect of the DRD2 C957T
polymorphism on P200 amplitude. Carriers of the TT genotype had higher P200
amplitudes compared to subjects with schizophrenia risk C allele. Within-group
comparisons demonstrated a better ability to adjust attention to orthographic
stimuli depending on task demands and lexicality in the TT group. CONCLUSION: The
results of the study suggest that the DRD2 C957T polymorphism modulates early
stages of visual word recognition.
PMID- 29945154
TI - Perioperative Acute Kidney Injury: Prevention, Early Recognition, and Supportive
Measures.
AB - BACKGROUND: Acute kidney injury (AKI) is a frequent complication of both cardiac
and major non-cardiac surgery. AKI is independently associated with morbidity,
mortality, and long-term adverse events including chronic kidney disease in
postsurgical patients. Since specific treatment options for kidney failure are
very limited, early identification, diagnosis, and renal support strategies are
key steps to improve patients' outcome. SUMMARY: According to current Kidney
Disease: Improving Global Outcomes (KDIGO) guidelines, AKI diagnosis is based on
2 functional markers, serum creatinine increase and urine output decrease, that
are not renal-specific and have important limitations. However, preoperative risk
stratification for postoperative AKI and/or early diagnosis after surgery could
be the best way to apply preventive or timely supportive therapeutic measures.
Clinical prediction scores, renal functional reserve assessment, and new
biomarkers of kidney stress (suppression of tumorigenicity-2, insulin-like growth
factor binding protein-7, tissue inhibitor metalloproteinase-2) may help the
clinicians to identify patients at risk of AKI and that could benefit from the
application of nephroprotective bundles suggested by the KDIGO guidelines. In
severe AKI patients with oligoanuria and fluid accumulation, renal replacement
therapy is the only supportive measure even if mode and timing remain open to
investigation. Key messages: Perioperative AKI is an important and underdiagnosed
complication. Identifying patients at high risk of AKI and diagnosing AKI early
are major goals. Preventive interventions are mainly based on the KDIGO
guidelines and bundles. Furthermore, a personalized multidisciplinary approach
should always be considered to minimize the progression of disease and the
complications related to kidney damage.
PMID- 29945155
TI - PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the
STAT3 Signalling Pathway.
AB - BACKGROUND/AIMS: Although it has been widely accepted that protein arginine
methyltransferase 1 (PRMT1) is a cancer-promoting gene in various cancers, the
mechanism of PRMT1 in hepatocellular carcinoma (HCC) requires more exploration.
This study aimed to investigate the role of PRMT1 in HCC growth and metastasis.
METHODS: We compared PRMT1 expression and clinicopathological characteristics
using paired HCC and adjacent noncancerous liver tissues from 210 patients and
immunohistochemistry analyses. Cell proliferation, colony formation and migration
were determined in HCC cell lines with PRMT1 overexpression or downregulation
through MTT, crystal violet and Boyden chamber assays. Tumour growth was
monitored in a xenograft model, and intrahepatic metastasis models were
established. RESULTS: PRMT1 expression was greatly increased in clinical HCC
samples and strongly associated with poor prognosis and recurrence; PRMT1
expression was also positively correlated with microvascular invasion (P =
0.024), tumour differentiation (P = 0.014), tumour size (P = 0.002), and portal
vein tumour thrombus (PVTT) (P = 0.028). Cell proliferation, colony formation and
migration in vitro were enhanced by PRMT1 upregulation and decreased by PRMT1
downregulation in HCC cell lines. Moreover, low PRMT1 expression resulted in slow
tumour growth and decreased tumour weight in vivo, as well as tumour metastasis.
These phenotypes were associated with STAT3 signalling pathway activation.
Cryptotanshinone, a STAT3 inhibitor, inhibited STAT3 phosphorylation and reversed
the HCC phenotype of PRMT1 expression. CONCLUSIONS: We revealed a significant
role for PRMT1 in HCC progression and metastasis in vitro and in vivo via STAT3
signalling pathway activation. PRMT1 may be a potential novel prognostic
biomarker and new therapeutic target for HCC.
PMID- 29945156
TI - German National Guideline for Treating Chronic Respiratory Failure with Invasive
and Non-Invasive Ventilation - Revised Edition 2017: Part 2.
AB - Today, invasive and non-invasive home mechanical ventilation have become a well
established treatment option. Consequently, in 2010, the German Respiratory
Society (DGP) has leadingly published the guidelines on "Non-Invasive and
Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure."
However, continuing technical evolutions, new scientific insights, and health
care developments require an extensive revision of the guidelines. For this
reason, the updated guidelines are now published. Thereby, the existing chapters,
namely technical issues, organizational structures in Germany, qualification
criteria, disease-specific recommendations including special features in
pediatrics as well as ethical aspects and palliative care, have been updated
according to the current literature and the health care developments in Germany.
New chapters added to the guidelines include the topics of home mechanical
ventilation in paraplegic patients and in those with failure of prolonged
weaning. In the current guidelines, different societies as well as professional
and expert associations have been involved when compared to the 2010 guidelines.
Importantly, disease-specific aspects are now covered by the German
Interdisciplinary Society of Home Mechanical Ventilation (DIGAB). In addition,
societies and associations directly involved in the care of patients receiving
home mechanical ventilation have been included in the current process.
Importantly, associations responsible for decisions on costs in the health care
system and patient organizations have now been involved.
PMID- 29945158
TI - HISTONE DEACETYLASE 19 and the flowering time gene FD maintain reproductive
meristem identity in an age-dependent manner.
AB - The shoot apical meristem (SAM) undergoes developmental transitions that include
a shift from vegetative to reproductive growth. This transition is triggered by
flowering time genes, which up-regulate floral meristem (FM) identity genes that,
in turn, control flower development by activating floral organ identity genes.
This cascade of transcriptional activation is refined by repression mechanisms
that temporally and spatially restrict gene expression to ensure proper
development. Here, we demonstrate that HISTONE DEACETYLASE 19 (HDA19) maintains
the identity of the reproductive SAM, or inflorescence meristem (IM), late in
Arabidopsis thaliana development. At late stages of growth, hda19 IMs display a
striking patterning defect characterized by ectopic expression of floral organ
identity genes and the replacement of flowers with individual stamenoid organs.
We further show that the flowering time gene FD has a specific function in this
regulatory process, as fd hastens the emergence of these patterning defects in
hda19 growth. Our work therefore identifies a new role for FD in reproductive
patterning, as FD regulates IM function together with HDA19 in an age-dependent
fashion. To effect these abnormalities, hda19 and fd may accentuate the weakening
of transcriptional repression that occurs naturally with reproductive meristem
proliferation.
PMID- 29945157
TI - Exposure to Upper Arm Elevation During Work Compared to Leisure Among 12
Different Occupations Measured with Triaxial Accelerometers.
AB - Regarding prevention of neck and shoulder pain (NSP), unsupported arm elevation
is one factor that should be taken into account when performing work risk
assessment. Triaxial accelerometers can be used to measure arm elevation over
several days but it is not possible to differentiate between supported and
unsupported arm elevation from accelerometers only. Supported arm elevation is
more likely to exist during sitting than standing. The aim of the study was to
evaluate the use of whole workday measurements of arm elevation with
accelerometers to assess potentially harmful work exposure of arm elevation, by
comparing arm elevation at work with arm elevation during leisure, in a
population with diverse work tasks, and to assess how the exposure parameters
were modified when upper arm elevation during sitting time was excluded. The
participants, 197 workers belonging to 12 occupational groups with diverse work
tasks, wore triaxial accelerometers on the dominant arm, hip, and back for 1-4
days to measure arm elevation and periods of sitting. None of the groups were
found to have higher exposure to arm elevation during work compared to leisure.
Even though some occupations where known to have work tasks that forced them to
work with elevated arms to a large extent. A high proportion of arm elevation
derived from sitting time, especially so during leisure. When arm elevation
during sitting time was excluded from the analysis, arm elevation was
significantly higher at work than during leisure among construction workers,
garbage collectors, manufacturing workers, and domestic cleaners. Together this
illustrates that it is not suitable to use whole workday measurments of arm
elevation with accelerometer as a sole information source when assessing the risk
for NSP due to arm elevation. Information on body posture can provide relevant
contextual information in exposure assessments when it is known that the
potential harmful exposure is performed in standing or walking.
PMID- 29945159
TI - Non-invasive testing in patients with suspected coronary artery disease: some may
be more equal than others.
PMID- 29945160
TI - Segmental Analysis of Chlorprothixene and Desmethylchlorprothixene in Postmortem
Hair.
AB - Analysis of drugs in hair differs from their analysis in other tissues due to the
extended detection window, as well as the opportunity that segmental hair
analysis offers for the detection of changes in drug intake over time. The
antipsychotic drug chlorprothixene is widely used, but few reports exist on
chlorprothixene concentrations in hair. In this study, we analyzed hair segments
from 20 deceased psychiatric patients who had undergone chronic chlorprothixene
treatment, and we report hair concentrations of chlorprothixene and its
metabolite desmethylchlorprothixene. Three to six 1-cm long segments were
analyzed per individual, corresponding to ~3-6 months of hair growth before
death, depending on the length of the hair. We used a previously published and
fully validated liquid chromatography-tandem mass spectrometry method for the
hair analysis. The 10th-90th percentiles of chlorprothixene and
desmethylchlorprothixene concentrations in all hair segments were 0.05-0.84 ng/mg
and 0.06-0.89 ng/mg, respectively, with medians of 0.21 and 0.24 ng/mg, and means
of 0.38 and 0.43 ng/mg. The estimated daily dosages ranged from 28 mg/day to 417
mg/day. We found a significant positive correlation between the concentration in
hair and the estimated daily doses for both chlorprothixene (P = 0.0016, slope =
0.0044 [ng/mg hair]/[mg/day]) and the metabolite desmethylchlorprothixene (P =
0.0074). Concentrations generally decreased throughout the hair shaft from
proximal to distal segments, with an average reduction in concentration from
segment 1 to segment 3 of 24% for all cases, indicating that most of the
individuals had been compliant with their treatment. We have provided some
guidance regarding reference levels for chlorprothixene and
desmethylchlorprothixene concentrations in hair from patients undergoing long
term chlorprothixene treatment.
PMID- 29945161
TI - William Withering's Portrait.
PMID- 29945162
TI - Safety and effectiveness of rivaroxaban and apixaban in patients with venous
thromboembolism: a nationwide study.
AB - Aims: To investigate the risk of all-cause mortality, recurrent venous
thromboembolism (VTE), and hospitalized bleeding in patients with VTE treated
with either rivaroxaban or apixaban. Methods and results: Using Danish nationwide
registries, patients with VTE treated with rivaroxaban or apixaban in the period
from 1 January 2015 to 30 June 2017 were identified. Standardized absolute risks
were estimated based on outcome-specific Cox regression models, adjusted for
potential confounders. A total of 8187 patients were included in the study, of
which 1504 (18%) were treated with apixaban [50% males, median age 70 years;
interquartile range (IQR) 56-80] and 6683 (82%) were treated with rivaroxaban
(55% males, median age 67 years; IQR 53-76). The 180 days risk of all-cause
mortality was 5.08% [95% confidence interval (95% CI) 4.08% to 6.08%)] in the
apixaban group and 4.60% (95% CI 4.13% to 5.18%) in the rivaroxaban group
[absolute risk difference: -0.48% (95% CI -1.49% to 0.72%)]. The 180 days risk of
recurrent VTE was 2.16% (95% CI 1.49% to 2.88%) in the apixaban group and 2.22%
(95% CI 1.89% to 2.52%) in the rivaroxaban group [absolute risk difference of
0.06% (95% CI -0.72% to 0.79%)]. The 180 days risk of hospitalized bleeding was
1.73% (95% CI 1.22% to 2.35%) for patients in the apixaban group and 1.89% (95%
CI 1.56% to 2.20%) in the rivaroxaban group [absolute risk difference: 0.16% (95%
CI -0.59% to 0.81%)]. Conclusion: In a nationwide cohort of 8187 patients with
VTE treated with rivaroxaban or apixaban, there were no significant differences
in the risks of all-cause mortality, recurrent VTE, or hospitalized bleeding.
PMID- 29945163
TI - Evaluation of cefazolin antimicrobial prophylaxis during cardiac surgery with
cardiopulmonary bypass-authors' response.
PMID- 29945164
TI - A new method for detection of single nucleotide polymorphism in a female
reproduction-associated gene, tmigd1, of Anas platyrhynchos using a strip
biosensor with gold nanoparticles.
AB - In this study, we first reported a lateral flow assay combined with primer
extension (PEXT) and gold nanoparticles for single-nucleotide polymorphism (SNP)
genotyping of the tmigd1 gene of the Tsaiya ducks (Anas platyrhynchos), which has
the advantages of simplicity of operation, cost-effectiveness, and time-saving.
Gold nanoparticles were tailed with thiol-thymine oligodeoxyribonucleotides
(thiol-(dT)30) using the salt-aging method at 25 degrees C and used as a label in
a lateral flow assay. The lateral flow device was composed of test and control
zones on a nitrocellulose membrane containing streptavidin and adenosine
oligodeoxyribonucleotides ((dA)30), respectively. When the specific SNP existed,
the corresponding primers were extended, and the reaction product was captured by
streptavidin at the test zone owing to the introduction of biotin-deoxyuridine
triphosphate (biotin-dUTP) into the reaction product during PEXT. Gold
nanoparticles hybridized with the reaction product to render it visible. Here, we
developed a new system for detection of single nucleotide polymorphism in a
female reproduction-associated gene, tmigd1, of Anas platyrhynchos using the
strip biosensor, and identified the optimized parameters for the concentration of
Mg2+ in the PEXT reaction and the amount of streptavidin used on membranes for
signal specificity.
PMID- 29945165
TI - The right chance for temozolomide in metastatic colorectal cancer?
PMID- 29945166
TI - Isolation and identification of specific bacteriophage against enteropathogenic
Escherichia coli (EPEC) and in vitro and in vivo characterization of
bacteriophage.
AB - In recent years, the increasing resistance of enteropathogenic Escherichia coli
(EPEC) to commonly used antibiotics has made it difficult to choose the best
treatment option. Bacteriophage therapy could be a potent alternative to
antibiotic therapy for antibiotic-resistant bacteria. The aim of the present
study was to isolate and identify a specific bacteriophage against
enteropathogenic E. coli (EPEC) and characterize bacteriophage in vitro and in
vivo. The specific bacteriophage was isolated and the effect of phage therapy on
48 mice (Balb/c) was investigated. Animals were divided into six groups,
including A: PBS (negative control), B: bacteria (positive control), C: bacteria
+ ciprofloxacin (after 24 hours), D: bacteria + bacteriophage (after 24 hours),
E: bacteria + ciprofloxacin + bacteriophage (after 24 hours), and F:
bacteriophage + bacteria (after 24 hours). Specific bacteriophage against EPEC
was isolated from hospital sewage. The bacteriophage had an icosahedral head (120
nm) and a tail (138 nm). The single dose of the bacteriophage (2 * 109 pfu ml-1)
was able to control the infection. Unfortunately, because of the misuse of
antibiotics by EPEC infected patients, the antibiotic resistant bacteria will
become prevalent in the future and the treatment of EPEC infection is going to
become more difficult than ever.
PMID- 29945167
TI - Erratum.
PMID- 29945168
TI - Quality of life and quality-adjusted life years of chronic schistosomiasis
mansoni patients in Brazil in 2015.
AB - Background: Measures of health-related quality of life (HRQoL) have been used to
express the impact of neglected diseases and to generate indicators for health
economic assessments. Schistosomiasis mansoni is a neglected disease with various
clinical manifestations, including severe repercussions, caused by parasitic
worms. Here we describe the quality of life of chronic schistosomiasis mansoni
patients and estimate the quality-adjusted life years (QALYs) associated with
chronic schistosomiasis mansoni in Brazil in 2015. Methods: A HRQoL study was
carried out using the three-level European Quality of Life 5-Dimensions (EQ-5D
3L) questionnaire in 147 chronic schistosomiasis mansoni patients at an
outpatient monitoring facility of an endemic state for schistosomiasis. Results:
Losses in HRQoL were observed in all five dimensions of the EQ-5D-3L. Patients
>60 y and 40-49 y of age reported the highest frequencies of problems. The
average utility index was 0.71, and the median index was significantly lower
among female patients and patients with comorbidities (0.68; p<0.05) compared
with the entire sample. Approximately 26.7 QALYs were estimated for the study
population and 31.2 QALYs for the chronic schistosomiasis mansoni patients in
Brazil. Conclusions: The advanced forms of schistosomiasis mansoni, even during
treatment, contribute to important health losses in the population dealing with
the disease.
PMID- 29945170
TI - Effects of Experimental Anthropogenic Noise Exposure on the Reproductive Success
of Secondary Cavity Nesting Birds.
AB - Artificial nest boxes are critical nesting sites for secondary cavity-nesting
birds; however, they are often placed near roadways and in urban areas that
experience noise pollution and other human-caused stressors. Recent correlative
studies document both negative and positive influences of noise pollution on
reproductive success. Additionally, observational studies have not determined
which stage of the breeding process is most vulnerable to noise pollution
settlement, incubation, and/or provisioning. Here, we controlled for possible
effects from non-random settlement and eliminated potential effects of roadways,
such as collisions and chemical and light pollution, by experimentally
introducing traffic noise into nest boxes after clutch initiation in two
secondary-cavity nesting bird species. We found no evidence for an influence of
noise on clutch size, brood size, number of fledglings, or overall nest success
in western bluebirds (Sialia mexicana). In contrast, we found that ash-throated
flycatcher (Myiarchus cinerascens) nests exposed to noise had lower reproductive
success than quiet nests due to higher rates of abandonment at the incubation
stage. Our results match recent research demonstrating that ash-throated
flycatchers avoid energy-sector noise in their nest placement and, when they do
nest in noise, experience stress hormone dysregulation and fitness costs. The
lack of a response among western bluebirds differs from reported declines in
reproductive success due to exposure to energy-sector noise; however, the absence
of a response matches the response seen in other species using an in-box noise
playback experiment. These results suggest that in-box noise exposure experiments
may be appropriate for assessing noise impacts at the nest, and through some
pathways (e.g., direct effects of noise on nestlings), but do not capture other
ways in which noise can negatively affect birds during the breeding season that
may ultimately cause declines in fitness. Additionally, although manipulative
experiments that examine the influence of a single anthropogenic stressor on a
single life stage can help reveal causal pathways, urban and other human
dominated environments are characterized by many stressors and future studies
should seek to understand how noise interacts with other stressors to impact
birds and other wildlife. Finally, in light of mounting evidence demonstrating
declines in reproductive success due to noise, our results suggest that nest box
placement near roads may be counterproductive to efforts to bolster population
densities of some species.
PMID- 29945169
TI - The Candidate Blood Stage Malaria Vaccine P27A Induces a Robust Humoral Response
in a Fast Track to the Field Phase I Trial in Exposed and Non Exposed Volunteers.
AB - Background: P27A is an unstructured 104mer synthetic peptide from P. falciparum
TEX1 blood-stage protein found to be the target of human antibodies inhibiting
parasite growth. The present project aimed at evaluating the safety and
immunogenicity of P27A peptide vaccine in malaria non-exposed European and
exposed African adults. Methods: This study was designed as a staggered, fast
track, randomized, antigen and adjuvant dose-finding, multi-center phase Ia/Ib
trial, conducted in Switzerland and in Tanzania. P27A antigen (10 or 50MUg),
adjuvanted with Alhydrogel(r) or GLA-SE (2.5 or 5MUg), or control rabies vaccine
(Verorab(r)) were administered intramuscularly to 16 malaria non-exposed and 40
exposed subjects on days 0, 28 and 56. Local and systemic adverse events (AEs) as
well as humoral and cellular immune responses were assessed after each injection
and during the 34-week follow-up. Results: Most AEs were mild to moderate and
resolved completely within 48 hours. Systemic AEs were more frequent in the
formulation with Alum as compared to GLA-SE, whereas local AE were more frequent
after GLA-SE. No serious AEs occurred. Supported by a mixed Th1/Th2 cell mediated
immunity, P27A induced a marked specific antibody response able to recognize TEX1
in infected erythrocytes and to inhibit parasite growth through an ADCI dependent
mechanism. Incidence of AEs and antibody responses were significantly lower in
malaria-exposed Tanzanian than in non-exposed European subjects. Conclusions: The
candidate vaccine P27A was safe and induced an immunogenic response that was
particularly robust in combination with GLA-SE. This formulation should be
considered for future efficacy trials. Clinical trial registration: This trial
was registered in clinicaltrials.gov (NCT01949909) and www.pactr.org
(PACTR201310000683408).
PMID- 29945171
TI - Nutritional evaluation of Glutenol: a co-product of ethanol production.
AB - The objective of this study was to evaluate the nutritional value of Glutenol, a
new coproduct of the ethanol industry. Glutenol was produced by Quality
Technology International, Elgin, IL, in a modified wet-milling plant using a
hybrid process, NextGenFrac, which fractionates the corn kernel components prior
to fermentation without the use of sulfur dioxide. Glutenol was analyzed to
contain 52.3% CP, 1.7% Met + Cys, 1.32% Lys, 1.69% Thr, and 2.23% Val on a DM
basis. Two precision-fed rooster assays with conventional and cecectomized
roosters were conducted to determine TMEn and standardized digestibility of amino
acids (AA), respectively. The TMEn of Glutenol was determined to be 3,256 kcal/kg
DM. Standardized digestibility values for Lys, Met, Cys, Thr, and Val were 80.1%,
90.4%, 80.1%, 74.1%, 81.1%, and 84.9%, respectively. In addition, a 3-wk broiler
chick assay was conducted with increasing levels of dietary Glutenol. Diet 1 was
a standard corn/soybean meal diet with 0% Glutenol. Diets 2, 3, and 4 had
increasing levels of Glutenol at 4%, 8%, and 12%, respectively. Diets were fed
from 3 to 22 d post-hatch and all diets were formulated to be equal in TMEn and
digestible AA. Weight gain, feed intake, and gain/feed ratio were measured. No
differences in growth performance were observed among dietary treatments. In
conclusion, Glutenol can be fed up to at least 12% in the diet of broiler
chickens if diets are formulated to be equal in ME and digestible AA.
PMID- 29945173
TI - Cellular targeting and segregation of bacterial chemosensory systems.
AB - The bacterial cytoplasm is not a homogeneous solution of macromolecules, but
rather a highly organized and compartmentalized space where the clustering and
segregation of macromolecular complexes in certain cell regions confers
functional efficiency. Bacterial chemoreceptors represent a versatile model
system to study the subcellular localization of macromolecules, as they are
present in almost all motile bacterial and archaeal species, where they tend to
form highly ordered arrays that occupy distinct positions in cells. The
positioning of chemoreceptor clusters, as well as their segregation mechanism on
cell division, varies from species to species and probably depends on cells size,
environment and speed of movement. In this review, we summarize the current
understanding of the architecture and the segregation mechanisms of
chemoreceptors in a limited number of bacterial model systems and suggest that
the pattern of chemoreceptor distribution is coupled to behavioral life-style of
that species.
PMID- 29945174
TI - N-terminal acetylation: an essential protein modification emerges as an important
regulator of stress responses.
AB - N-terminal acetylation (NTA) is a prevalent protein modification in eukaryotes.
The majority of proteins are acetylated at their N-terminus in a co-translational
manner by ribosome-associated N-terminal acetyltransferases (NATs). However, the
recent discovery of Golgi membrane-localized NATs in metazoa, and plastid
localized NATs in plants challenged the dogma of static, co-translational
imprinting of the proteome by NTA. Indeed, NTA by the cytosolic NatA is highly
dynamic and under hormonal control in plants. Such active control has not been
evidenced yet in other eukaryotes and might be an adaptation to the sessile
lifestyle of plants forcing them to cope with diverse environmental challenges.
The function of NTAs for individual proteins is distinct and yet unpredictable.
In yeast and humans, NTA has been shown to affect protein-protein interactions,
subcellular localization, folding, aggregation, or degradation of a handful of
proteins. In particular, the impact of NTA on the protein turnover is documented
by diverse examples in yeast. Consequently, NTA was recently dicovered to be a
degradation signal in a distinct branch of the N-end rule pathway, ubiquitin
mediated proteolysis. In this review, we summarize the current knowledge on the
NAT machinery in higher plants and discuss the potential function of NTA during
biotic and abiotic stresses.
PMID- 29945172
TI - Phylogeny and staminal evolution of Salvia (Lamiaceae, Nepetoideae) in East Asia.
AB - Background and Aims: Salvia is the largest genus within Lamiaceae, with about 980
species currently recognized. East Asia, with approx. 100 species, is one of the
three major biodiversity centres of Salvia. However, relationships within this
lineage remain unclear, and the staminal lever mechanism, which may represent a
key innovation within the genus, has been understudied. By using six genetic
markers and nearly comprehensive taxon sampling, this study attempts to elucidate
relationships and examine evolutionary trends of staminal development within the
East Asia (EA) Salvia clade. Methods: Ninety-one taxa of EA Salvia were sampled
and 34 taxa representing all other major lineages of Salvia were included for
analysis. Two nuclear [internal transcribed spacer (ITS) and external transcribed
spacer (ETS)] and four chloroplast (psbA-trnH, ycf1-rps15, trnL-trnF and rbcL)
DNA markers were used for phylogenetic analysis employing maximum parsimony (MP),
maximum likelihood (ML) and BEAST, with the latter also used to estimate
divergence times. Key Results: All Salvia species native to East Asia form a
clade, and eight major subclades (A-G) were recognized. Subclade A, comprising
two limestone endemics (S. sonchifolia and S. petrophila), is sister to the
remainder of EA Salvia. Six distinct stamen types were observed within the EA
clade. Stamen type A, with two fully fertile posterior thecae, only occurs in S.
sonchifolia and may represent the ancestral stamen type within EA Salvia.
Divergence time estimates showed that the crown of EA Salvia began to diversify
approx. 17.4 million years ago. Conclusions: This study supports the adoption of
a broadly defined Salvia and treats EA Salvia as a subgenus, Glutinaria,
recognizing eight sections within this subgenus. Stamen type A is ostensibly
plesiomorphic within EA Salvia, and the other five types may have been derived
from it. Staminal morphology has evolved in parallel within the EA Salvia, and
staminal structure alone is inadequate to delimit infrageneric categories.
PMID- 29945176
TI - Oesophageal necrosis after thoracic endovascular aortic repair: a minimally
invasive endovascular approach-a dramatic complication.
AB - There are few cases in the literature reporting dysphagia caused by oesophageal
compression by the aorta due to acute or chronic aortic pathology. This type of
dysphagia is called dysphagia aortica. Thoracic endovascular aortic repair is
nowadays the treatment of choice for anatomically suitable patients experiencing
complicated Type B aortic dissection. Oesophageal necrosis is a rare but fatal
complication following thoracic endovascular aortic repair. Extrinsic oesophageal
compression by the thrombosed aneurysmal sac, a mediastinal haematoma or
extensive thrombosis in the false lumen of a dissected aorta and acute vascular
occlusion of the oesophageal supply are possible mechanisms. When oesophageal
necrosis is suspected, endoscopic examination and computed tomography imaging
should be performed repeatedly. Oesophagoscopy will confirm the diagnosis
revealing a black, diffusely necrotic and ulcerated oesophageal mucosa. It is
critical to intervene before full-thickness oesophageal wall necrosis and
mediastinitis occur. Guidelines are absent because of the rarity of this
complication. Moreover, lack of a large series does not permit the establishment
of guidelines either. However, oesophagectomy of the impaired oesophagus is the
only chance for survival. Unfortunately, survival rates are disappointing.
Prevention and awareness is the cornerstone of success. Early endoscopic
examination when oesophageal necrosis is suspected due to even minimal symptoms
will detect this fatal menace on time.
PMID- 29945177
TI - The antimicrobial spectrum of lysozyme broadened by reductive modification.
AB - In order to broaden the antimicrobial action spectrum of lysozyme against Gram
negative bacteria, different partially reduced lysozyme derivatives were obtained
by reducing the R-S-S-R bonds of lysozyme using the reducing agent Na2SO3. The
circular dichroism behavior analysis showed that the tertiary structure of the
partially reduced lysozyme molecules became more flexible, leading to an obvious
increase in the surface hydrophobicity and the tryptophan fluorescence intensity.
Zeta potential analysis indicated that the introduction of SO32- led to a
decrease in the surface charges of the reduced lysozyme molecules. Compared with
the native lysozyme, the reduced lysozymes not only showed a 1 log increase in
the antimicrobial activity against Escherichia coli ATCC 25922 and Salmonella
enteritidis ATCC 13076 (P <0.05), but also maintained nearly the same
antimicrobial activity against Staphylococcus aureus ATCC 29213 (P >0.05).
Overall, the reductive modification with the food-friendly, compatible, and safe
reducing agent Na2SO3 has broadened the antimicrobial action spectrum of the
modified lysozymes against Gram-negative bacteria, with the enhancement extent
depending on the reduction degree and the type of bacterial strains. The
integrated results suggest that the Na2SO3-reduced lysozyme can be used as a
novel safe potential bactericidal additive for food-processing industry.
PMID- 29945178
TI - Prediction of human-Bacillus anthracis protein-protein interactions using multi
layer neural network.
AB - Motivation: Triplet amino acids have successfully been included in feature
selection to predict human-HPV protein-protein interactions (PPI). The utility of
supervised learning methods is curtailed due to experimental data not being
available in sufficient quantities. Improvements in machine learning techniques
and features selection will enhance the study of PPI between host and pathogen.
Results: We present a comparison of a neural network model versus SVM for
prediction of host-pathogen PPI based on a combination of features including:
amino acid quadruplets, pairwise sequence similarity, and human interactome
properties. The neural network and SVM were implemented using Python Sklearn
library. The neural network model using quadruplet features and other network
features outperformance the SVM model. The models are tested against published
predictors and then applied to the human-B.anthracis case. Gene ontology term
enrichment analysis identifies immunology response and regulation as functions of
interacting proteins. Conclusion: For prediction of Human-viral PPI, our model
(neural network) is a significant improvement in overall performance compared to
a predictor using the triplets feature and achieves a good accuracy in predicting
human-B.anthracis PPI. Availability: All code can be downloaded from
ftp://ftp.sanbi.ac.za/machine_learning/. Supplementary information: Supplementary
data are available at ftp://ftp.sanbi.ac.za/machine_learning/.
PMID- 29945179
TI - Biotechnology of extremely thermophilic archaea.
AB - Although the extremely thermophilic archaea (Topt >= 70 degrees C) may be the
most primitive extant forms of life, they have been studied to a limited extent
relative to mesophilic microorganisms. Many of these organisms have unique
biochemical and physiological characteristics with important biotechnological
implications. These include methanogens that generate methane, fermentative
anaerobes that produce hydrogen gas with high efficiency, and acidophiles that
can mobilize base, precious and strategic metals from mineral ores. Extremely
thermophilic archaea have also been a valuable source of thermoactive,
thermostable biocatalysts, but their use as cellular systems has been limited
because of the general lack of facile genetics tools. This situation has changed
recently, however, thereby providing an important avenue for understanding their
metabolic and physiological details and also opening up opportunities for
metabolic engineering efforts. Along these lines, extremely thermophilic archaea
have recently been engineered to produce a variety of alcohols and industrial
chemicals, in some cases incorporating CO2 into the final product. There are
barriers and challenges to these organisms reaching their full potential as
industrial microorganisms but, if these can be overcome, a new dimension for
biotechnology will be forthcoming that strategically exploits biology at high
temperatures.
PMID- 29945180
TI - Thiosemicarbazone of lapachol acts on cell membrane in Paracoccidioides
brasiliensis.
AB - Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin
American countries. Amphotericin B, sulfonamides, and azoles may be used in the
treatment of PCM. However, the high toxicity, prolonged course of treatment, and
significant frequency of disease relapse compromise their use. Therefore, there
is a need to seek new therapeutic options. We conducted tests with
thiosemicarbazone of lapachol (TSC-lap) to determine the antifungal activity and
phenotypic effects against several isolates of Paracoccidioides spp. In addition,
we evaluated the toxicity against murine macrophages and the ability to enhance
phagocytosis. Further, we verified that TSC-lap was active against yeasts but did
not show any interaction with the drugs tested. The TSC-lap showed no toxicity at
the concentration of 40 MUg/ml in macrophages, and at 15.6 MUg/ml it could
increase the phagocytic index. We observed that this compound induced in vitro
ultrastructural changes manifested as withered and broken cells beyond a
disorganized cytoplasm with accumulation of granules. We did not observe
indications of activity in the cell wall, although membrane damages were noted.
We observed alterations in the membrane permeability, culminating in a
significant increase in K+ efflux and a gradual loss of the cellular content with
increase in the concentration of TSC-lap. In addition, we showed a significant
reduction of ergosterol amount in the Pb18 membrane. These data reinforce the
possible mechanism of action of this compound to be closely associated with
ergosterol biosynthesis and reaffirms the antifungal potential of TSC-lap against
Paracoccidioides spp.
PMID- 29945181
TI - Are the proprotein convertase subtilisin/kexin type 9 inhibitors new therapeutic
chance for patients with familial hypercholesterolaemia and liver failure?
PMID- 29945182
TI - Adduct Formation-Supported Two-Way Electrospray Ionization Strategy for the
Determination of Urinary Creatinine Concentration with LC-MS-MS in Abstinence
Control.
AB - In this work, an alternative LC-MS-MS strategy for the analysis of urinary
creatinine in abstinence control was presented and discussed. The two-way
electrospray ionization consisted of two different precursor ions in which
fragmentation was used in multiple reaction monitoring experiments. A creatinine
adduct ion with sodium and sodium acetate together with the conventional analyte
protonation was investigated. Adduct formation and fragmentation was explored by
appropriate infusion experiments performed with analyte solutions prepared in
different concentrations. The analytical signal was compensated by the
application of appropriate isotopically labeled internal standard. The advantages
of information carried by precursor ions separated in the mass spectra were
pointed out. Sample preparation based solely on sample dilution performed in the
final HPLC vial directly. A Luna 5 MUm C18 (2) 100 A, 150 mm * 2 mm analytical
column together with a mobile phase consisted of H2O/methanol = 3%/97% (v/v) with
10 mmol/L ammonium acetate and 0.1% acetic acid (flow = 0.4 mL/min) were used for
the separation performed during a run of 5 min. The linearity was examined in the
range of 100-3,000 mg/L. The limit of detection (13 mg/L), limit of
quantification (43 mg/L) together with method precision/accuracy, selectivity,
stability and matrix effect were tested to be appropriate for forensic
applications. The applicability of water as surrogate matrix for method
calibration was also examined successfully. The presented strategy was used in
the analysis of real samples. No interferences with the creatinine peak eluted at
about 1.0 min could be recorded.
PMID- 29945183
TI - Essential physiological differences characterise short- and long-lived strains of
Drosophila melanogaster.
AB - Aging is a multifactorial process which affects all animals. Aging as a result of
damage accumulation is the most accepted explanation but the proximal causes
remain to be elucidated. There is also evidence indicating that aging has an
important genetic component. Animal species age at different rates and specific
signalling pathways, such as insulin/insulin-like growth factor, can regulate
lifespan of individuals within a species by reprogramming cells in response to
environmental changes. Here, we use an unbiased approach to identify novel
factors that regulate lifespan in Drosophila melanogaster. We compare the
transcriptome and metabolome of two wild-type strains used widely in aging
research: short-lived Dahomey and long-lived Oregon R flies. We found that
Dahomey flies carry several traits associated with short-lived individuals and
species such as increased lipoxidative stress, decreased mitochondrial gene
expression and increased Target of Rapamycin signalling. Dahomey flies also have
upregulated octopamine signalling known to stimulate foraging behaviour.
Accordingly, we present evidence that increased foraging behaviour, under
laboratory conditions where nutrients are in excess increases damage generation
and accelerates aging. In summary, we have identified several new pathways, which
influence longevity highlighting the contribution and importance of the genetic
component of aging.
PMID- 29945184
TI - Geographic Variability in Discharge Setting and Outpatient Postacute Physical
Therapy After Total Knee Arthroplasty: A Retrospective Cohort Study.
AB - Background: Despite the frequency of total knee arthroplasty (TKA) in the
Medicare population, little is known about the use of postacute physical therapy
among those discharged to home. Objective: The objectives of this study were to
explore factors associated with geographic variability in discharge disposition
and outpatient physical therapy utilization for Medicare patients after TKA
discharged to home/self-care. Design: The design of the study was a retrospective
cohort study. Methods: Medicare patients with TKA discharged alive from July 1,
2010, to June 30, 2011, with discharge disposition to home/self-care (HSC), home
health agency (HHA), inpatient rehabilitation facility (IRF), or skilled nursing
facility (SNF) were selected. Geography was measured with Census region.
Outpatient physical therapy utilization was calculated from Medicare Part B
claims. Odds ratios for discharge disposition and adjusted means for physical
therapy utilization variables by Census region were calculated, accounting for
county-clustered data and adjusting for demographics, clinical, and environmental
characteristics. Results: There was significant variation with discharge
destination by Census region among 18,278 patients. With discharge disposition
analysis, the patients from the West region who were discharged home were the
referent group. The patients from the South and Northeast regions had higher odds
for discharge to HHAs (adjusted odds ratio [95% CI = 1.80 [1.48-2.19] and 2.20
[1.70-2.84]), SNFs (1.34 [1.08-1.66] and 4.42 [3.38-5.79]), and IRFs (2.36 [1.80
3.09] and 8.83 [6.41-12.18]). For those discharged to HSC, 40.4% received
outpatient physical therapy within 4 weeks. Significant differences were found
with time to first physical therapy visit (Midwest 1 Gy old clade). Analysis of the data resulting
from these single-cell 'omics approaches show: 1) the description of the ciliates
in the class Karyorelictea as "primitive" is inaccurate because their somatic
macronuclei contain loci of varying copy number (i.e., they have been processed
by genome rearrangements from the zygotic nucleus); 2) gene-sized somatic
chromosomes exist in the class Litostomatea, consistent with Balbiani's (1890)
observation of giant chromosomes in this lineage; and 3) gene scrambling exists
in the underexplored Postciliodesmatophora (the classes Heterotrichea and
Karyorelictea, abbreviated here as the Po-clade), one of two major clades of
ciliates. Together these data highlight the complex evolutionary patterns
underlying germline genome architectures in ciliates and provide a basis for
further exploration of principles of genome evolution in diverse microbial
lineages.
PMID- 29945195
TI - Integrated methodological approach reveals microbial diversity and functions in
aerobic groundwater microcosms adapted to vinyl chloride.
AB - Vinyl chloride (VC), a known human carcinogen, is often formed in groundwater
(GW) by incomplete reductive dechlorination of chlorinated ethenes. An integrated
microbial ecology approach involving bacterial enrichments and isolations, carbon
stable-isotope probing (SIP) and metagenome and genome sequencing was applied to
ethene-fed GW microcosms that rapidly transitioned to aerobic growth on VC.
Actinobacteria, Proteobacteria and Bacteroidetes dominated the microbial
communities in ethene- and VC-grown cultures. SIP with 13C2-VC demonstrated that
Nocardioides spp. significantly participated in carbon uptake from VC (52.1%
75.7% enriched in heavy fractions). Sediminibacterium, Pedobacter and Pseudomonas
spp. also incorporated 13C from VC into genomic DNA. Ethene- and VC-assimilating
Nocardioides sp. strain XL1 was isolated. Sequencing revealed a large (~300 kbp)
plasmid harboring genes encoding alkene monooxygenase and epoxyalkane: coenzyme M
transferase, enzymes known to participate in aerobic VC and ethene
biodegradation. The plasmid was 100% identical to pNOCA01 found in VC
assimilating Nocardioides sp. strain JS614. Metagenomic analysis of enrichment
cultures indicated other bacteria implicated in carbon uptake from VC possessed
the genetic potential to detoxify epoxides via epoxide hydrolase or glutathione S
transferase (Pseudomonas) and/or metabolize VC epoxide breakdown products and
downstream VC metabolites. This study provides new functional insights into
aerobic VC metabolism within a GW microbial community.
PMID- 29945196
TI - A new approach to study attached biofilms and floating communities from
Pseudomonas aeruginosa strains of various origins reveals diverse effects of
divalent ions.
AB - Pseudomonas aeruginosa is an opportunistic pathogen associated with nosocomial
infections and disease complications. In the lungs of cystic fibrosis (CF)
individuals, biofilm growth plays a crucial role in the persistence and
antibiotic resistance of P. aeruginosa. Some strains, adapted to the CF lung
microenvironment, show distinguishable phenotypes linked to biofilm production
when compared to other strains. Using a novel image analysis quantification
approach with crystal violet-stained biofilms, we compared the biofilm formation
of four different P. aeruginosa isolates in 24-well plates: PAO1, the reference
strain, LESB58 from CF patients' lungs and PPF-1 and Urg-7, two environmental
isolates from dental unit waterlines. We also observed the formation of biofilm
like structures (BLSs) floating in the medium and investigated growth inhibition
of the attached biofilm and BLS with Mg2+ or Zn2+. Urg-7 produced the most
attached biofilms, but not the most BLSs. Attached biofilms had different
responses to cations than BLSs did, but the effect of the cations was similar for
all strains. These results demonstrate some diversity of biofilm formation in P.
aeruginosa and indicate that chemical inhibition of attached biofilm formation
for a specific strain or isolate cannot be predicative of a result on other P.
aeruginosa strains or on BLSs.
PMID- 29945197
TI - A Case Study Involving U-47700, Diclazepam and Flubromazepam-Application of
Retrospective Analysis of HRMS Data.
AB - The number of new psychoactive substances (NPS) available is constantly
increasing, making it difficult for toxicology laboratories to keep screening
methods up to date. Full scan high-resolution mass spectrometry (HRMS) is a
versatile technique which allows for progressive updating of spectral databases
to increase the scope of screening. It also allows for retrospective screening of
data-specifically, reprocessing of data files using an updated spectral database
without the need for re-extraction or reanalysis.The coronial case reported here
illustrates the application of retrospective processing of HRMS data in the
detection of emerging NPS. A 28-year-old male with a history of illicit drug use
was found deceased at home. Initial routine screening of the post-mortem
peripheral blood identified only methylamphetamine, amphetamine and trace amounts
of lorazepam. A compound with an accurate mass and isotope ratio consistent with
the opioid AH-7921 was also detected in the liquid chromatography (LC)-HRMS
screen; however; the retention time and mass spectrum did not match the library.
Further investigation confirmed the compound to be U-47700, another opioid and
structural isomer of AH-7921. Several months later, after additional NPS had been
added to the in-house HRMS database, retrospective screening of the HRMS data was
performed, revealing the presence of designer benzodiazepines, diclazepam and
flubromazepam as well as the psychedelic drug 2,5-dimethoxy-4-chloroamphetamine
(DOC). Quantitative analysis gave the following results in peripheral post-mortem
blood: U-47700 (330 MUg/L), diclazepam (70 MUg/L), flubromazepam (10 MUg/L),
methylamphetamine (290 MUg/L) and amphetamine (150 MUg/L) (DOC not quantitated).
These substances, along with lorazepam and etizolam, were also confirmed in the
post-mortem urine and an investigation into blood and urinary metabolites was
carried out. All analyses were performed using the same LC-quadrupole-time of
flight method. The cause of death was aspiration (of gastric content into airways
and lungs) due to mixed drug toxicity.
PMID- 29945199
TI - Insecticide Susceptibility in Tuta absoluta (Lepidoptera: Gelechiidae) and
Metabolic Characterization of Resistance to Diazinon.
AB - The tomato leafminer, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a
globally important economic insect pest of tomatoes that has rapidly expanded in
range. The pest is generally controlled by insecticides; however, reduced
susceptibility of T. absoluta to many recommended insecticides has been reported.
The aims of this study were to determine the efficacy of diazinon, spinosad,
abamectin, and Bt on second instar larvae of Iranian greenhouse populations of T.
absoluta from Soufian (SF) and Qom (QM) and a susceptible (SS) population
originally from Bonab, and assess the possibility of resistance in the
populations. The results showed that spinosad was the most effective insecticide,
whereas in contrast, Bt was ineffective against the populations. Abamectin was
effective, but susceptibility in SF population was lower than in QM and SS.
Susceptibility to diazinon was low in SF and QM populations. Mediation of
diazinon resistance by metabolic mechanisms and activity of detoxifying enzymes
and acetylcholinesterase on resistance were assessed. The results showed that
enhanced activity of monooxygenases and esterases may have played a role in
resistance of T. absoluta to diazinon. Our results will be useful in resistance
management in this injurious pest and reduce the negative impacts of high rates
of insecticide use on the environment.
PMID- 29945198
TI - Toward predictive R-loop computational biology: genome-scale prediction of R
loops reveals their association with complex promoter structures, G-quadruplexes
and transcriptionally active enhancers.
AB - R-loops are three-stranded RNA:DNA hybrid structures essential for many normal
and pathobiological processes. Previously, we generated a quantitative R-loop
forming sequence (RLFS) model, quantitative model of R-loop-forming sequences
(QmRLFS) and predicted ~660 000 RLFSs; most of them located in genes and gene
flanking regions, G-rich regions and disease-associated genomic loci in the human
genome. Here, we conducted a comprehensive comparative analysis of these RLFSs
using experimental data and demonstrated the high performance of QmRLFS
predictions on the nucleotide and genome scales. The preferential co-localization
of RLFS with promoters, U1 splice sites, gene ends, enhancers and non-B DNA
structures, such as G-quadruplexes, provides evidence for the mechanical linkage
between DNA tertiary structures, transcription initiation and R-loops in critical
regulatory genome regions. We introduced and characterized an abundant class of
reverse-forward RLFS clusters highly enriched in non-B DNA structures, which
localized to promoters, gene ends and enhancers. The RLFS co-localization with
promoters and transcriptionally active enhancers suggested new models for in cis
and in trans regulation by RNA:DNA hybrids of transcription initiation and
formation of 3D-chromatin loops. Overall, this study provides a rationale for the
discovery and characterization of the non-B DNA regulatory structures involved in
the formation of the RNA:DNA interactome as the basis for an emerging
quantitative R-loop biology and pathobiology.
PMID- 29945200
TI - Prevention of Colony Establishment by the West Indian Drywood Termite Using
Reduced Rates of Borate and Silica Dust or Solution.
AB - Imago dispersal by the West Indian drywood termite, Cryptotermes brevis (Walker)
(Isoptera: Kalotermitidae) potentially initiates or expands structural
infestations by the establishment of incipient colonies. The prevention of
drywood termite colonization in structures is difficult, but a substantial
reduction may be obtainable. In this experiment, seasonal dispersal of C. brevis
imagos commenced from infested wood in a laboratory building. A bioassay was
developed to determine the efficacy of 100, 50, and 10% label rate applications
of a borate (Tim-Bor) and silica (CimeXa) dust or solution against C. brevis
colony establishment under these simulated field conditions. All treatments
prevented colony establishment at label rate applications, whereas Tim-bor
significantly reduced colonization at all exposure rates.
PMID- 29945201
TI - Effects of Bacillus subtilis and zinc on the growth performance, internal organ
development, and intestinal morphology of male broilers with or without
subclinical coccidia challenge.
AB - Effects of antibiotic (bacitracin), anticoccidial (narasin), and alternative
(Bacillus subtilis and zinc) feed additives on growth performance, internal organ
development, and intestinal morphology of commercial broilers with or without
subclinical coccidia challenge were determined. A total of 1,344 1-day-old male
Ross * Ross 708 broilers were randomly distributed into 12 treatments (6 diets *
2 challenge treatments, 8 replication pens/treatment) in 96 floor pens. The 6
dietary treatments were as follows: a control diet (corn and soybean-meal basal
diet), a probiotic diet (basal diet + Bacillus subtilis), a zinc diet (basal diet
+ 100 ppm zinc), a probiotic and zinc combined diet, an anticoccidial diet (basal
diet + narasin), and a practical diet (basal diet + narasin + bacitracin). On day
21, each chick in the challenge treatment was gavaged with a 10* dose of a
commercial vaccine containing live Eimeria oocytes, whereas each chick in the non
challenge treatment was gavaged with equivalent distilled water. The subclinical
coccidia challenge increased the relative weights of pancreas and decreased the
ileal crypt depth of broilers at 26 d of age, increased feed conversion ratios
from day 15 to 28 and 29 to 40, and increased the relative weights of duodenum
and bursa on day 54. As compared to other diets, anticoccidial and practical
diets increased BW gain and decreased feed conversion ratio from day 15 to 28,
and increased the day 40 carcass weights. As compared to control diets, probiotic
diets decreased BW gain and increased the mortality from day 15 to 28; however,
probiotic diets did not affect the overall growth performance from day 0 to 54 or
carcass yield on day 54. Growth measurements during periods of day 29 to 40 and
day 41 to 54 were not affected by any feed additive. From this study, a
subclinical coccidia challenge enlarged specific internal organs and compromised
the feed conversion ability of broilers. Dietary Bacillus subtilis did not affect
overall growth rate or carcass yield of broilers under subclinical coccidia
challenge.
PMID- 29945204
TI - Endovascular repair for inflammatory abdominal aortic aneurysm.
PMID- 29945205
TI - Comment on: Evaluation of cefazolin antimicrobial prophylaxis during cardiac
surgery with cardiopulmonary bypass.
PMID- 29945202
TI - The Revised National Alzheimer's Coordinating Center's Neuropathology Form
Available Data and New Analyses.
AB - Neuropathologic evaluation remains the gold standard for determining the presence
and severity of aging-related neurodegenerative diseases. Researchers at U.S.
Alzheimer's Disease Centers (ADCs) have worked for >30 years studying human
brains, with the goals of achieving new research breakthroughs. Harmonization and
sharing among the 39 current and past ADCs is promoted by the National
Alzheimer's Coordinating Center (NACC), which collects, audits, and disburses ADC
derived data to investigators on request. The past decades have witnessed revised
disease definitions paired with dramatic expansion in the granularity and
multimodality of the collected data. The NACC database now includes cognitive
test scores, comorbidities, drug history, neuroimaging, and links to genomics.
Relatively, recent advances in the neuropathologic diagnoses of Alzheimer's
disease, frontotemporal lobar degeneration (FTLD), and vascular contributions to
cognitive impairment and dementia catalyzed a 2014 update to the NACC
Neuropathology Form completed by all ADCs. New focal points include
cerebrovascular disease (including arteriolosclerosis, microbleeds, and
microinfarcts), hippocampal sclerosis, TDP-43, and FTLD. Here, we provide summary
data and analyses to illustrate the potential for both hypothesis-testing and
also generating new hypotheses using the NACC Neuropathology data set, which
represents one of the largest multi-center databases of carefully curated
neuropathologic information that is freely available to researchers worldwide.
PMID- 29945203
TI - Ixekizumab improves patient-reported outcomes up to 52 weeks in bDMARD-naive
patients with active psoriatic arthritis (SPIRIT-P1).
AB - Objective: To report patient-reported outcomes of patients with PsA treated with
ixekizumab up to 52 weeks. Methods: In SPIRIT-P1, biologic-naive patients with
active PsA were randomized to ixekizumab 80 mg every 4 weeks (IXEQ4W; N = 107) or
every 2 weeks (IXEQ2W; N = 103) following a 160 mg starting dose, adalimumab 40
mg every 2 weeks (ADA; N = 101) or placebo (PBO; N = 106) during the initial 24
week double-blind treatment period. At week 24 (week 16 for inadequate
responders), ADA (8-week washout before starting ixekizumab) and PBO patients
were re-randomized to IXEQ2W or IXEQ4W. Patients receiving ixekizumab at week 24
received the same dose during the extension period (EP) to week 52. Patients
completed measures including the Dermatology Life Quality Index (DLQI), Itch
Numeric Rating Scale, 36-Item Short Form Health Survey version 2, European
Quality of Life 5 Dimensions Visual Analogue Scale and Work Productivity and
Activity Impairment Questionnaire-Specific Health Problem. Results: The IXEQ4W,
IXEQ2W and ADA groups reported significant improvements in DLQI at week 24; 22%
(PBO), 53% (IXEQ4W), 63% (IXEQ2W) and 54% (ADA) of patients reported DLQI scores
of 0/1. The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in
Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2 physical
component summary and some domain scores, and European Quality of Life 5
Dimensions Visual Analogue Scale at weeks 12 and 24; and in three of four Work
Productivity and Activity Impairment Questionnaire-Specific Health Problem
domains at week 24. Results are also presented through week 52 for the EP.
Conclusion: In biologic-naive patients with active PsA, ixekizumab significantly
improved skin symptoms, health-related quality of life and work productivity.
Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239;
EU Clinical Trials Register, https://www.clinicaltrialsregister.eu, EudraCT2011
002326-49.
PMID- 29945206
TI - Igf3 serves as a mediator of LH in zebrafish ovulation.
AB - Both oocyte maturation and ovulation is triggered by the luteinizing hormone (LH)
surge in vertebrates, but exactly how these processes are regulated by LH remains
to be fully elucidated. Previously we found that Igf3, a fish-specific member of
the igf family predominantly expressed in the gonads, could mediate the action of
LH on oocyte maturation in zebrafish. Here, we further reveal the importance of
Igf3 in mediating the action of LH on ovulation in zebrafish. All the four igf
gene family members are expressed in the zebrafish ovary but only the igf3
transcript level is increased in hCG-induced ovulation in vivo. The expression of
Igf3 protein in the follicles is also increased during ovulation. The actions of
hCG on the expression of ovulatory enzymes and on ovulation itself could be
largely mimicked by the recombinant zebrafish Igf3 protein. Intriguingly, the
phosphorylation of Igf1r, the receptor for Igf3, could be activated by hCG in the
follicular cells during ovulation. And inhibition of Igf3 signaling by Igf1r
inhibitors and Igf3 antiserum could significantly attenuate the hCG-induced
ovulation. Collectively, all these data support the notion that Igf3 serves as a
mediator of LH action in zebrafish ovulation.
PMID- 29945207
TI - Lifetime productivity of conventionally and precision-fed broiler breeders.
AB - A precision feeding (PF) system was developed to increase broiler breeder
lifetime reproductive performance through improved flock uniformity. The current
study consisted of 2 rearing and 3 laying treatments. From 0 to 22 wk of age, 480
Cobb male grandparent line pullets and 80 Cobb MX males were fed once daily as a
group (CON), or individually with a PF system. Pullets were housed in 6 replicate
pens of 40 birds, and cockerels in one pen per treatment. During lay, CON and PF
treatments continued, and a third treatment was added, where PF-reared birds were
transitioned to conventional feeding (PFCON; n = 3 pens). At photostimulation (22
wk of age), all pens had 24 hens and 2 roosters. Birds were allowed to mate
naturally to 52 wk. Analysis of variance was conducted, and Tukey-adjusted means
were reported as different where P <= 0.05. Mean BW was near the target BW in all
treatments. At photostimulation, PF pullet BW CV was 2% vs 14% in CON pullets.
Cumulative feed conversion ratio during rearing was lower in PF treatment
pullets, which ate 3% less than CON pullets. Pullets in the PF treatment received
10 meals spread throughout each day, compared with one meal per day in the CON
treatment. Increased feeding frequency would reduce diurnal fluctuations in
nutrient supply, which may explain why PF pullets had 1.2 times the breast muscle
weight of CON pullets at 22 wk. There was no treatment difference in abdominal
fatpad weight at 22 wk. The PF treatment had 3.8% higher fertility and 1.3% lower
egg weight CV compared with the CON treatment. Egg production in PF and PFCON
treatments was 0.73 and 0.89 times that of the CON treatment, respectively. It is
hypothesized that metabolic changes in PF pullets provided an insufficient
metabolic trigger for sexual maturation. It follows that relaxing feed
restriction may increase fat deposition and egg production in PF broiler
breeders.
PMID- 29945208
TI - An Overview of Molecular Profiles in Ulcerative Colitis-Related Cancer.
AB - Ulcerative colitis (UC) is an independent risk factor of colorectal cancer (CRC).
Both genetic and epigentic events induce a unique molecular profile during the
development from UC to UC-related CRC (UCRC). These molecular changes play varied
roles in DNA repair, immune response, cell metabolism, and interaction with the
microbiota during the carcinogenesis process. This review will systmatically
discuss the molecular characteristics of UCRC and point out the future
perspectives in this research field.
PMID- 29945209
TI - A functional genetic screen reveals sequence preferences within a key tertiary
interaction in cobalamin riboswitches required for ligand selectivity.
AB - Riboswitches are structured mRNA sequences that regulate gene expression by
directly binding intracellular metabolites. Generating the appropriate regulatory
response requires the RNA rapidly and stably acquire higher-order structure to
form the binding pocket, bind the appropriate effector molecule and undergo a
structural transition to inform the expression machinery. These requirements
place riboswitches under strong kinetic constraints, likely restricting the
sequence space accessible by recurrent structural modules such as the kink turn
and the T-loop. Class-II cobalamin riboswitches contain two T-loop modules: one
directing global folding of the RNA and another buttressing the ligand binding
pocket. While the T-loop module directing folding is highly conserved, the T-loop
associated with binding is substantially less so, with no clear consensus
sequence. To further understand the functional role of the binding-associated
module, a functional genetic screen of a library of riboswitches with the T-loop
and its interacting nucleotides was used to build an experimental phylogeny
comprised of sequences that possess a wide range of cobalamin-dependent
regulatory activity. Our results reveal conservation patterns of the T-loop and
its interaction with the binding core that allow for rapid tertiary structure
formation and demonstrate its importance for generating strong ligand-dependent
repression of mRNA expression.
PMID- 29945210
TI - SC1 inhibits the differentiation of F9 embryonic carcinoma cells induced by
retinoic acid.
AB - The ability to self-renew is one of the most important properties of embryonic
stem (ES) cells. Pluripotin (SC1), a small molecule with high activity and low
toxicity, promotes self-renewal in mouse ES cells. SC1 can noticeably change the
morphology of retinoic acid (RA)-induced F9 embryonic carcinoma cells (F9 cells).
However, in the long term, RA and SC1 together cause cell apoptosis. When being
added after 18-24 h of RA-induced F9 cell differentiation, SC1 transitorily
activated Nanog and Oct4. Both Nanog and Oct4 were downregulated when SC1 and RA
were added simultaneously. On the other hand, Klf4 was continually activated when
SC1 was added between 6 and 24 h. Phosphorylated Erk1/2 protein levels were
reduced from 6 to 24 h, whereas unphosphorylated Erk1 protein levels remained
unchanged. A higher concentration of SC1 promoted cell self-renewal by
strengthening the inhibition of Erk1/2 protein phosphorylation in F9 cells.
Furthermore, SC1 and RA affect global DNA methylation by influencing the
expressions of methylation-associated proteins, including Dnmt3b, Dnmt3l, Tet1,
Tet2, and Tet3. In conclusion, SC1 inhibits the differentiation of RA-induced F9
cells mainly by reducing the levels of phosphorylated Erk1/2 and enhancing the
expression of Klf4, although it also reduces DNA methylation, which may have an
additional effect on ES cell differentiation.
PMID- 29945211
TI - beta-Cypermethrin and its metabolite 3-phenoxybenzoic acid induce cytotoxicity
and block granulocytic cell differentiation in HL-60 cells.
AB - The most widely used type II pyrethroid is beta-cypermethrin (beta-CYP), and 3
phenoxybenzoic acid (3-PBA) is one of its primary metabolites. Although CYP has
been shown to pose toxic effects in some immune cells, as of now the
immunotoxicity of CYP on immune progenitor cells has not been well studied. In
this study, we evaluated the immunotoxicity of beta-CYP and 3-PBA on the human
promyelocytic leukemia cell line, HL-60. Both beta-CYP and 3-PBA reduced cell
viability. In addition, both beta-CYP and 3-PBA stimulated the intrinsic
apoptotic pathway in a dose- and time-dependent manner, while only beta-CYP
induced cell cycle arrest in G1 stage. Moreover, exposure to beta-CYP and 3-PBA
at 100 MUM inhibited all-trans retinoic acid (ATRA)-induced mRNA expressions of
the granulocytic differentiation-related genes, CD11b and CSF-3R. Furthermore,
exposure to beta-CYP and 3-PBA resulted in a downregulation of the granulocytic
differentiation promoting transcriptional factors, PU.1 and C/EBPepsilon.
Furthermore, we found that beta-CYP and 3-PBA exposure led to elevated levels of
cellular reactive oxygen species (ROS), and that pretreatment with N
acetylcysteine (NAC) blocked the toxic effects caused by beta-CYP and 3-PBA. The
results obtained in the present study provide evidence showing the immunotoxic
effects of beta-CYP and 3-PBA on promyelocytic cells as well as its possible
underlying mechanism.
PMID- 29945212
TI - Anti-thrombotic options for secondary prevention in patients with chronic
atherosclerotic vascular disease: what does COMPASS add?
PMID- 29945213
TI - Effects of Potassium Fertilizer Rates on Soybean Looper (Lepidoptera: Noctuidae)
Development.
AB - Potassium (K) has an important impact on physiological and biochemical processes
in plants. Soybean, Glycine max (L.) Merrill, requires high K availability for
optimal yield. However, changes in nutrient availability in plants may also
affect herbivore population size and/or development. Soybean looper, Chrysodeixis
includens (Walker) (Lepidoptera: Noctuidae), is one of the most destructive pests
of soybean in the southern United States. In this study, we evaluated the effects
of different K fertilization rates on soybean looper development, soybean seed
weight, and soybean seed nutritional quality. Soybean plants were supplied with
six different rates of K fertilizer (0, 33.6, 67.3, 100.9, 134.5, and 168.1 kg/ha
as K2O). Soybean leaves were sampled at R1, R3, R5, and R6 stages and fed to
soybean looper in laboratory bioassays. Soybean looper mortality, fecundity, and
fertility were not significantly affected by feeding on leaf tissues of soybean
treated with different potassium fertilizer rates. However, soybean looper
consumed more leaf tissue and spent less time completing larval development when
fed on foliage from treatments of 134.5 and 168.1 kg/ha. Pupal weight
significantly increased at 134.5 and 168.1 kg/ha. There was no significant
difference in percentage of protein, oil, and fiber in soybean seeds among six K
fertilizer rates. Percentage of K in soybean seeds and 100 seed weight were
significantly enhanced at 168.1 kg/ha. Nitrogen (N) content of foliage was not
affected by applying K fertilizer at different rates. Our results indicate that
higher K fertilizer rates can enhance soybean seed weight but also facilitate
soybean looper development.
PMID- 29945215
TI - TMEPAI family: involvement in regulation of multiple signalling pathways.
AB - The TMEPAI family, composed of TMEPAI and C18ORF1, is known to inhibit
transforming growth factor-beta (TGF-beta) signalling via its competition for
binding of receptor-regulated Smad with Smad anchor for receptor activation.
However, TMEPAI has also been reported to be involved in androgen receptor
signalling, phosphatase and tensin homologue deleted on chromosome 10 signalling,
and formation of autophagosomes in addition to degradation of TbetaRI (TGF-beta
type I receptor) through lysosomes. Thus, TMEPAI seems to act as a regulator of
multiple signalling pathways. A great deal of attention has already been paid to
the relationship between the TMEPAI family and tumourigenicity. In this paper,
therefore, we describe recent progresses in the understanding of how the TMEPAI
family physiologically contributes to cellular functions and diseases.
PMID- 29945216
TI - Host Plant Infection by Soybean Mosaic Virus Reduces the Fitness of Its Vector,
Aphis glycines (Hemiptera: Aphididae).
AB - Coevolutionary interactions between pathogens and their insect vectors can
dramatically impact the fitness of herbivorous insects and patterns of plant
disease transmission. Soybean mosaic virus (SMV) is a common disease in soybean
production worldwide. Infected seed is the primary source of inoculum in fields
and the virus is secondarily spread among plants by the soybean aphid, Aphis
glycines Matsumura (Hemiptera: Aphididae), in a nonpersistent manner. In this
study, we compared the biological fitness of A. glycines colonizing both SMV
infected and uninfected soybean plants. Aphids feeding on SMV-infected soybean
seedlings were significantly smaller and lighter than those feeding on uninfected
plants across life stages. SMV infection caused delayed development of aphid
nymphs on soybean seedlings, but this was more than compensated by a reduction in
the pre-reproductive period of apterous adults. The fecundity of A. glycines was
reduced when feeding on SMV-infected seedlings, resulting in a lower reproductive
rate, a longer generation time, and a slower population doubling time. A smaller
proportion of aphid offspring developed into alatae when feeding on SMV-infected
soybean seedling, and these took longer to mature than their counterparts on
uninfected plants. We infer that SMV infection has significantly negative effects
on the biological performance of A. glycines, which may be consistent with the
long-term coevolution of SMV, soybean, and A. glycines in the transmission cycle
of SMV.
PMID- 29945217
TI - Role of surgical manipulation in lung inflammatory response in a model of lung
resection surgery.
AB - OBJECTIVES: Lung resection surgery with one-lung ventilation leads to an
inflammatory response. Surgical manipulation can play a key role in this
response. Sevoflurane, a commonly used volatile anaesthetic, has a proven anti
inflammatory effect. Our main goal was to evaluate the segregated effect of
surgical manipulation during lung resection surgery and the protective role of
sevoflurane with regard to this response. METHODS: Fifteen pigs underwent left
thoracotomy for caudal lobectomy under general anaesthesia. The animals were
divided into 3 groups: control, sevoflurane and sham. The animals in the sham
group underwent left thoracotomy and one-lung ventilation over 120 min, without
lobectomy. The animals in the sevoflurane group received anaesthetic maintenance
with sevoflurane. The animals in the sham group and the control group received
propofol during the procedure. Lung biopsies were collected before the procedure
(left caudal lobe) and 24 h later (right mediastinal lobe and left upper lobe).
The samples were stored to measure levels of inflammatory markers (IL-1, TNF
alpha and ICAM-1), apoptotic mediators (BAD, BAX, BCL-2 and Caspase-3), Syndecan
1, MicroRNAs 182, 145 and lung oedema. RESULTS: Surgical manipulation increased
the expression of inflammation (IL-1, TNF-alpha and ICAM-1) and proapoptotic
mediators (BAX, BAD and Caspase-3). It also caused degradation of endothelial
glycocalyx (Syndecan-1) and pulmonary oedema. Administration of sevoflurane
reduced the elevation of inflammatory markers, degradation of glycocalyx and
pulmonary oedema observed in the control group. CONCLUSIONS: Surgical
manipulation of the collapsed lung could increase the expression of inflammation
and proapoptotic mediators and cause tissue damage in the form of pulmonary
oedema. Sevoflurane could attenuate this molecular response and pulmonary oedema.
PMID- 29945218
TI - Can mindfulness in health care professionals improve patient care? An integrative
review and proposed model.
AB - Mindfulness in health care professionals (HCPs) is often discussed as a tool for
improving patient care outcomes, yet there has not been a critical evaluation of
the evidence, despite a growing body of research on mindfulness-based
interventions (MBIs). Numerous mechanisms exist by which mindfulness in HCPs may
have an effect on patient care, and the field lacks an integrated model to guide
future investigations into how MBIs may exert effects. The primary goals of this
integrative review are to evaluate the evidence for the impact of MBIs in HCPs on
patient care outcomes and to propose a causal model to guide future research.
Databases were systematically searched for eligible studies investigating either
an MBI or a measure of dispositional mindfulness in HCPs on patient care
outcomes. Studies were critically evaluated using a previously developed tool.
Twenty-six studies were identified (N = 1,277), which provide strong support for
effects of mindfulness on HCP-reported patient care. Moderate support was found
for patient safety, patient treatment outcomes, and patient-centered care. There
was overall weak evidence to support a relationship between HCP-mindfulness on
patient satisfaction. Mindfulness in HCPs may be related to several aspects of
patient care.
PMID- 29945219
TI - Pulmonary saddle thrombus.
PMID- 29945220
TI - Phylodynamic model adequacy using posterior predictive simulations.
AB - Rapidly evolving pathogens, such as viruses and bacteria, accumulate genetic
change at a similar timescale over which their epidemiological processes occur,
such that it is possible to make inferences about their infectious spread using
phylogenetic time-trees. For this purpose it is necessary to choose a
phylodynamic model. However, the resulting inferences are contingent on whether
the model adequately describes key features of the data. Model adequacy methods
allow formal rejection of a model if it cannot generate the main features of the
data. We present TreeModelAdequacy (TMA), a package for the popular BEAST2
software, that allows assessing the adequacy of phylodynamic models. We
illustrate its utility by analysing phylogenetic trees from two viral outbreaks
of Ebola and H1N1 influenza. The main features of the Ebola data were adequately
described by the coalescent exponential-growth model, whereas the H1N1 influenza
data was best described by the birth-death SIR model.
PMID- 29945221
TI - Effects of dietary yeast nucleotides supplementation on intestinal barrier
function, intestinal microbiota, and humoral immunity in specific pathogen-free
chickens.
AB - Yeast nucleotides are a fine functional additive in human and animals. The
effects of dietary yeast nucleotides supplementation on intestinal development,
expression of intestinal barrier-related genes, intestinal microbiota, and
infectious bronchitis virus (IBV) antibody titer of specific pathogen-free (SPF)
chickens were investigated. A total of 60 1-d-old chickens were divided into 4
groups, each of which included 3 replicates of 5 chickens. Group 1 served as a
control that was fed a basal diet. Groups 2 to 4 were fed the basal diet
supplemented with 0.1%, 0.3% and 0.5% yeast nucleotides, respectively. All
chickens were inoculated intranasally with inactivated IBV vaccine at day 1 and
day 10. At day 17, the intestinal development, expression of intestinal barrier
related genes and microbiota were evaluated. There was a significant increased
ileal villus height and villus height to crypt depth ratio in group 2 (P < 0.05).
Moreover, group 4 exhibited higher expression of zonula occludens-1 (ZO-1) and
Occludin gene in ileum (P < 0.05), whereas groups 2 and 3 exhibited higher
expression of Mucin 2 (MUC2) and trefoil factor 2 (TFF2) gene (P < 0.05), group 2
showed lower expression of IFN-alpha gene (P < 0.05). Dietary yeast nucleotides
increased intestinal bacterial diversity (P < 0.05), and the abundance of
Lactobacillus (P < 0.05). At day 10, 17, 24, 31, 38, and 45, the serum IBV
antibody titers were tested. Group 2 exhibited higher IBV antibody titer at day
17 (P < 0.05), furthermore, groups 2 to 4 reached the effective levels 1 wk
earlier than control group. In conclusion, dietary yeast nucleotides
supplementation can help birds to mount a faster and stronger antibody response
to IBV vaccine. In addition, dietary yeast nucleotides supplementation can also
promote the intestinal development and barrier-related genes expression, and
diversity and richness of intestinal microbiota.
PMID- 29945222
TI - Cysteine-X-Cysteine Motif Chemokine Ligand 12 and Its Receptor CXCR4: Expression,
Regulation, and Possible Function at the Maternal-Conceptus Interface during
Early Pregnancy in Pigs.
AB - Cysteine-X-cysteine (CXC) motif chemokine ligand 12 (CXCL12) and its receptor,
CXC chemokine receptor type 4 (CXCR4), are involved in regulating the
proliferation, migration, and survival of trophoblast cells and the maternal
immune response in humans and mice. The present study examined the expression,
regulation, and function of CXCL12 and CXCR4 at the maternal-conceptus interface
during pregnancy in pigs. The endometrium expressed CXCL12 and CXCR4 mRNAs with
the greatest CXCL12 abundance on Day 15 of pregnancy. CXCL12 protein was
localized mainly in endometrial epithelial cells, while CXCR4 protein was
localized in subepithelial stromal cells, vascular endothelial cells, and immune
cells in blood vessels in the endometrium during the estrous cycle and pregnancy.
CXCL12 protein was detected in uterine flushing on Day 15 of pregnancy. The
conceptus during early pregnancy and chorioallantoic tissues during mid- to late
pregnancy expressed CXCL12 and CXCR4. Interferon-gamma increased the abundance of
CXCL12, but not CXCR4 mRNA in endometrial explants. Recombinant CXCL12 (rCXCL12)
protein dose-dependently increased migration of cultured porcine trophectoderm
cells and peripheral blood mononuclear cells (PBMCs). Furthermore, rCXCL12 caused
migration of T cells, but not natural killer cells, in PBMCs. This study revealed
that interferon-gamma-induced CXCL12 and its receptor, CXCR4, were expressed at
the maternal-conceptus interface and increased the migration of trophectoderm
cells and T cells at the time of implantation in pigs. These results suggest that
CXCL12 may be critical for the establishment of pregnancy by regulating
trophoblast migration and T cell recruitment into the endometrium during the
implantation period in pigs.
PMID- 29945226
TI - Probabilistic Physiologically Based Pharmacokinetic Model for Penicillin G in
Milk From Dairy Cows Following Intramammary or Intramuscular Administrations.
AB - Penicillin remains one of the most frequently identified violative drug residues
in food-producing animals. The predominant violations of penicillin were found in
cull dairy cows. In the United States, procaine penicillin G is approved to be
used in dairy cows through intramuscular (IM) and intramammary (IMM)
administrations. Physiologically based pharmacokinetic (PBPK) models are useful
tools to predict withdrawal intervals and tissue residues of drugs in food
animals to ensure food safety, especially for extralabel drug use due to the
scarcity of experimental data after extralabel administrations. Currently, no
PBPK model is available to predict penicillin concentrations in milk. A
population PBPK model with a physiologically based compartment for the mammary
gland was established for penicillin G in dairy cows. The model predicted the
tissue and milk residues well based on comparison with data from previous
pharmacokinetic studies. The predicted milk discard interval of procaine
penicillin G administered at 10 times the label dose for 3 repeated IM
administrations was 182 h, and 122 h at 4 times the label dose after 3 repeated
IMM infusions. Predicted results showed that even 4 times label dose did not lead
to violative tissue residues in healthy dairy cows with IMM infusions. The
predominant violations found in cull dairy cows may be caused by altered
pharmacokinetics due to mastitis, other diseases, and/or interactions with other
drugs, which have impacts on penicillin distribution and elimination. The current
PBPK model can help predict milk discard interval for penicillin following
extralabel use through IM and IMM administrations.
PMID- 29945223
TI - The effect of the DISC1 Ser704Cys polymorphism on striatal dopamine synthesis
capacity: an [18F]-DOPA PET study.
AB - Whilst the role of the Disrupted-in-Schizophrenia 1 (DISC1) gene in the aetiology
of major mental illnesses is debated, the characterization of its function lends
it credibility as a candidate. A key aspect of this functional characterization
is the determination of the role of common non-synonymous polymorphisms on normal
variation within these functions. The common allele (A) of the DISC1 single
nucleotide polymorphism (SNP) rs821616 encodes a serine (ser) at the Ser704Cys
polymorphism, and has been shown to increase the phosphorylation of extracellular
signal-regulated protein Kinases 1 and 2 (ERK1/2) that stimulate the
phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme for dopamine
biosynthesis. We therefore set out to test the hypothesis that human ser (A)
homozygotes would show elevated dopamine synthesis capacity compared with
cysteine (cys) homozygotes and heterozygotes (TT and AT) for rs821616. [18F]-DOPA
positron emission tomography (PET) was used to index striatal dopamine synthesis
capacity as the influx rate constant Kicer in healthy volunteers DISC1 rs821616
ser homozygotes (N = 46) and healthy volunteers DISC1 rs821616 cys homozygotes
and heterozygotes (N = 56), matched for age, gender, ethnicity and using three
scanners. We found DISC1 rs821616 ser homozygotes exhibited a significantly
higher striatal Kicer compared with cys homozygotes and heterozygotes (P = 0.012)
explaining 6.4% of the variance (partial eta2 = 0.064). Our finding is consistent
with its previous association with heightened activation of ERK1/2, which
stimulates tyrosine hydroxylase activity for dopamine synthesis. This could be a
potential mechanism mediating risk for psychosis, lending further credibility to
the fact that DISC1 is of functional interest in the aetiology of major mental
illness.
PMID- 29945224
TI - Ribosome elongating footprints denoised by wavelet transform comprehensively
characterize dynamic cellular translation events.
AB - Translation is dynamically regulated during cell development and stress response.
In order to detect actively translated open reading frames (ORFs) and dynamic
cellular translation events, we have developed a computational method, RiboWave,
to process ribosome profiling data. RiboWave utilizes wavelet transform to
denoise the original signal by extracting 3-nt periodicity of ribosomes and
precisely locate their footprint denoted as Periodic Footprint P-site (PF P
site). Such high-resolution footprint is found to capture the full track of
actively elongating ribosomes, from which translational landscape can be
explicitly characterized. We compare RiboWave with several published methods,
like RiboTaper, ORFscore and RibORF, and found that RiboWave outperforms them in
both accuracy and usage when defining actively translated ORFs. Moreover, we show
that PF P-site derived by RiboWave shows superior performance in characterizing
the dynamics and complexity of cellular translatome by accurately estimating the
abundance of protein levels, assessing differential translation and identifying
dynamic translation frameshift.
PMID- 29945225
TI - Metabolites of n-Butylparaben and iso-Butylparaben Exhibit Estrogenic Properties
in MCF-7 and T47D Human Breast Cancer Cell Lines.
AB - Two oxidized metabolites of n-butylparaben (BuP) and iso-butylparaben (IsoBuP)
discovered in human urine samples exhibit structural similarity to endogenous
estrogens. We hypothesized that these metabolites bind to the human estrogen
receptor (ER) and promote estrogen signaling. We tested this using models of ER
mediated cellular proliferation. The estrogenic properties of 3-hydroxy n-butyl 4
hydroxybenzoate (3OH) and 2-hydroxy iso-butyl 4-hydroxybenzoate (2OH) were
determined using the ER-positive, estrogen-dependent human breast cancer cell
lines MCF-7, and T47D. The 3OH metabolite induced cellular proliferation with
EC50 of 8.2 uM in MCF-7 cells. The EC50 for 3OH in T47D cells could not be
reached. The 2OH metabolite induced proliferation with EC50 of 2.2 uM and 43.0 uM
in MCF-7 and T47D cells, respectively. The EC50 for the parental IsoBuP and BuP
was 0.30 and 1.2 uM in MCF-7 cells, respectively. The expression of a pro
proliferative, estrogen-inducible gene (GREB1) was induced by these compounds and
blocked by co-administration of an ER antagonist (ICI 182, 780), confirming the
ER-dependence of these effects. The metabolites promoted significant ER-dependent
transcriptional activity of an ERE-luciferase reporter construct at 10 and 20 uM
for 2OH and 10 uM for 3OH. Computational docking studies showed that the paraben
compounds exhibited the potential for favorable ligand-binding domain
interactions with human ERalpha in a manner similar to known x-ray crystal
structures of 17beta-estradiol in complex with ERalpha. We conclude that the
hydroxylated metabolites of BuP and IsoBuP are weak estrogens and should be
considered as additional components of potential endocrine disrupting effects
upon paraben exposure.
PMID- 29945227
TI - Metabolic and Phenotypic Characterization of Human Skin Fibroblasts After Forcing
Oxidative Capacity.
AB - Human skin fibroblasts present technical advantages for the study of
mitochondrial-induced toxicity, because those cells can be isolated from patients
by lowly invasive methods and present specific cumulative cellular damage and
mutations of particular conditions. Several drugs lead to organ toxicity, with
some of these drugs having been already withdrawn from the market. Frequently,
drug-induced toxicity is attributed to mitochondrial liabilities. One of the
approaches to identify drug-induced mitochondrial toxicity is using glucose
free/galactose/glutamine/pyruvate-containing cell culture media that force cells
to be more dependent on oxidative phosphorylation for energy production. However,
the effects of this modified culture medium itself on the mitochondrial phenotype
of human skin fibroblasts have not been explored in detail. Our objective was to
assess the mitochondrial biology of human skin fibroblasts under standard or
modified culture conditions so that system can be validated and used in a more
reliable way to disclose mitochondrial liabilities of drug candidates or
intrinsic metabolic differences in fibroblasts. Our results showed that forcing
mitochondrial remodeling in human skin fibroblasts increased oxygen consumption
rate, ATP levels, and mitochondria-related transcripts and proteins. Moreover,
the metabolic remodeling increased cytotoxicity of mitochondrial poisons. In
general, no alterations in gene expression related with differentiation status
were observed in human skin fibroblasts, with exception of increased paxilin gene
expression. Not only the current work highlights the importance of using human
skin primary cells to study drug-induced mitochondrial toxicity, it also
reinforces the use of this tool to detect specific mitochondrial defects in skin
fibroblasts from patients.
PMID- 29945228
TI - Mixed "Antiandrogenic" Chemicals at Low Individual Doses Produce Reproductive
Tract Malformations in the Male Rat.
AB - Biomonitoring efforts have clearly shown that all humans are exposed to chemical
mixtures. Of concern is whether or not exposure to mixtures during pregnancy
contributes to congenital abnormalities in children even when each chemical is at
an individual dose that does not affect the fetus. Here, we hypothesized that in
utero exposure to a mixture of chemicals covering multiple "antiandrogenic"
mechanisms of action at doses that individually have no adverse effect would
result in permanent reproductive tract alterations in the male rat after birth.
Pregnant dams were exposed to a range of dilutions (100%, 50%, 25%, 12.5%, 6.25%,
or vehicle control) of a mixture containing pesticides, phthalates, and drugs (p,
p'-DDE, linuron, prochloraz, procymidone, pyrifluquinazon, vinclozolin,
finasteride, flutamide, simvastatin, and 9 phthalates [dipentyl, dicyclohexyl, di
2-ethylhexyl, dibutyl, benzyl butyl, diisobutyl, diisoheptyl, dihexyl, and
diheptyl]). The top dose contained each chemical at 20% of its lowest observed
adverse effect level (LOAEL) for the most sensitive male reproductive alteration
following in utero exposure. We found that male rat offspring displayed a variety
of neonatal, pubertal, and permanent adult effects across all dose levels. Even
at the lowest dose (each chemical approximately 80-fold below lowest observed
adverse effect level) there were permanent reductions in several reproductive
tract tissue weights. In the top dose group, 100% of male offspring displayed
permanent severe birth defects including genital malformations. Despite acting
via 5 different molecular initiating events, a mixture of 18 chemicals can
combine to produce additive effects even when each compound is at is at a
relatively low dose.
PMID- 29945229
TI - Effects of In Utero and Lactational Exposure to New Generation Green Plasticizers
on Adult Male Rats: A Comparative Study With Di(2-Ethylhexyl) Phthalate.
AB - Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, is a ubiquitous
environmental contaminant and may act as an endocrine disruptor. Early life
exposures to DEHP may result in anti-androgenic effects, impairing the
development of the male reproductive tract. However, data on the long-lasting
consequences of such DEHP exposures on adult male reproductive function are still
rare and discrepant. Previously, we identified 2 novel plasticizers, 1,4
butanediol dibenzoate (BDB) and dioctyl succinate (DOS), as potential substitutes
for DEHP that did not reproduce classically described endocrine disrupting
phenotypes in prepubertal male offspring after maternal exposure. Here, we
investigated the consequences of in utero and lactational exposure to BDB and DOS
on adult male rat reproductive function in a comparative study with DEHP and a
commercially available alternative plasticizer, 1,2-cyclohexane dicarboxylic acid
diisononyl ester (DINCH). Timed pregnant Sprague Dawley rats were gavaged with
vehicle or a test chemical (30 or 300 mg/kg/day) from gestation day 8 to
postnatal day 21. While DEHP exposure (300 mg/kg/day) significantly increased
epididymal weight in the adult, exposure to DINCH, BDB, or DOS did not affect
reproductive organ weights, steroid levels, or sperm quality. Using a
toxicogenomic microarray approach, we found that adult testicular gene expression
was affected by exposure to the higher dose of DEHP; transcripts such as Nr5a2,
Ltf, or Runx2 were significantly downregulated, suggesting that DEHP was
targeting estrogen signaling. Lesser effects were observed after treatment with
either DINCH or BDB. DOS exposure did not produce such effects, confirming its
potential as a responsible substitute for DEHP.
PMID- 29945230
TI - Baclofen-Induced Neuro-Respiratory Toxicity in the Rat: Contribution of Tolerance
and Characterization of Withdrawal Syndrome.
AB - Baclofen, a gamma-amino-butyric acid type-B receptor agonist with exponentially
increased use at high-dose to facilitate abstinence in chronic alcoholics, is
responsible for increasing poisonings. Tolerance and withdrawal syndromes have
been reported during prolonged treatment but their contribution to the
variability of baclofen-induced neurotoxicity in overdose is unknown. We studied
baclofen-induced effects on rat sedation, temperature, and ventilation and
modeled baclofen pharmacokinetics and effect/concentration relationships aiming
to investigate the consequences of repeated baclofen pretreatment and to
characterize withdrawal syndrome. Baclofen-induced dose-dependent sedation (p
<0.01), hypothermia (p <.001) and respiratory depression (p <.01) were altered in
repeatedly baclofen-pretreated rats (p <.05). Repeatedly baclofen-pretreated rats
did not exhibit respiratory depression following baclofen overdose due to
limitations on baclofen-induced increase in inspiratory (p <.01) and expiratory
times (p <.01). Only slight hypoxemia without respiratory acidosis was observed.
Baclofen discontinuation resulted in hyperlocomotion and non-anxiogenic
withdrawal symptoms. Regarding pharmacokinetics, repeated baclofen pretreatment
increased the peak concentration (p <.05) and absorption constant rate (p <.05)
and reduced the distribution volume (p <.0001) and elimination half-life (p
<.05). Analysis of the effect/concentration relationships indicated that plasma
baclofen concentration decreases more rapidly than all studied neuro-respiratory
effects, in tolerant and non-tolerant rats. Taken together, our findings
supported the role of brain distribution in baclofen-induced neurotoxicity
expression and its probable involvement in tolerance-related attenuation in
addition to physiological adaptations of ventilation. In conclusion, repeated
pretreatment attenuates baclofen-attributed neurotoxicity in overdose and results
in post-discontinuation withdrawal syndrome. Our findings suggest both
pharmacodynamic and pharmacokinetic mechanisms whose relative contributions to
the variability of baclofen-induced neurotoxicity in overdose remain to be
established.
PMID- 29945231
TI - Historical Highlights of Air Pollution Toxicology.
AB - Air pollution has a compelling history in the development of human cultures.
Fossil fuels opened a new human cultural chapter of extraordinary technical and
economic growth while bringing about noxious and unhealthful combustion
byproducts to breathe. Toxicology saw its birth in the modern world with
demonstrating the potential harmful effects of breathing smoke in its various
forms. The empirical nature of toxicology provided insights and underpinnings to
epidemiological studies providing biological plausibility and relative risk
attributions. As toxicology evolves with its sister sciences, there will be gains
in fundamental understandings of susceptibility and potential long-term risks of
air pollution with revelation of potential interventions and remedies for those
affected.
PMID- 29945232
TI - Early-drug development in the era of immuno-oncology: are we ready to face the
challenges?
AB - The classical development of drugs has progressively faded away, and we are
currently in an era of seamless drug-development, where first-in-human trials
include unusually big expansion cohorts in the search for early signs of activity
and rapid regulatory approval. The fierce competition between different
pharmaceutical companies and the hype for immune combinations obliges us to
question the current way in which we are evaluating these drugs. In this review,
we discuss critical issues and caveats in immunotherapy development. A particular
emphasis is put on the limitations of pre-clinical toxicology studies, where both
murine models and cynomolgus monkeys have underpredicted toxicity in humans.
Moreover, relevant issues surrounding dose determination during phase I trials,
such as dose-escalation methods or flat versus body-weight dosing, are discussed.
A proposal of how to face these different challenges is offered, in order to
achieve maximum efficacy with minimum toxicity for our patients.
PMID- 29945233
TI - appreci8: A Pipeline for Precise Variant Calling Integrating 8 Tools.
AB - Motivation: The application of next-generation sequencing in research and
particularly in clinical routine requires valid variant calling results. However,
evaluation of several commonly used tools has pointed out that not a single tool
meets this requirement. False positive as well as false negative calls
necessitate additional experiments and extensive manual work. Intelligent
combination and output filtration of different tools could significantly improve
the current situation. Results: We developed appreci8, an automatic variant
calling pipeline for calling single nucleotide variants and short indels by
combining and filtering the output of eight open-source variant calling tools,
based on a novel artifact- and polymorphism score. Appreci8 was trained on two
data sets from patients with myelodysplastic syndrome, covering 165 Illumina
samples. Subsequently, appreci8's performance was tested on five independent data
sets, covering 513 samples. Variation in sequencing platform, target region and
disease entity was considered. All calls were validated by re-sequencing on the
same platform, a different platform or expert-based review. Sensitivity of
appreci8 ranged between 0.93 and 1.00, while positive predictive value (PPV)
ranged between 0.65 and 1.00. In all cases, appreci8 showed superior performance
compared to any evaluated alternative approach. Availability: Appreci8 is freely
available at https://hub.docker.com/r/wwuimi/appreci8/. Sequencing data (BAM
files) of the 678 patients analyzed with appreci8 have been deposited into the
NCBI Sequence Read Archive (BioProjectID: 388411;
https://www.ncbi.nlm.nih.gov/bioproject/PRJNA388411). Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29945234
TI - Effect of gpd box copy numbers in the gpdA promoter of Aspergillus nidulans on
its transcription efficiency in Aspergillus niger.
AB - In this study, we characterised PgpdA, PgpdA2B, PgpdA3B and PgpdA4B promoters,
containing 1-4 copies of gpd box by modifying the gpdA promoter, and constructed
pSZHGX-xynB expression vectors, which were introduced into Aspergillus niger
CICC2462 through Agrobacterium-mediated transformation. Thus, An (PgpdA-xynB), An
(PgpdA2B-xynB), An (PgpdA3B-xynB) and An (PgpdA4B-xynB) homozygous recombinant
strains were obtained. The xylanase activity of homozygous recombinant strains
was measured. The enzymatic activities of An (PgpdA-xynB), An (PgpdA2B-xynB), An
(PgpdA3B-xynB) and An (PgpdA4B-xynB) peaked on the 7th day of fermentation, at
1578.67, 2333.88, 3588.38 and 3183.51 U.mL-1, respectively. SDS-PAGE and qRT-PCR
analysis indicated that An (PgpdA3B-xynB), containing three copies of gpd box,
demonstrated the highest levels of protein expression and transcription. These
results suggested that the PgpdA3B promoter promotes highly efficient
transcription and may serve as a strong constitutive promoter for efficient
recombinant protein expression. Additionally, a number of constitutive promoters
with various transcription efficiencies were identified for the metabolic
engineering of A. niger. Accordingly, this study provides a new approach for
obtaining promoters with different transcription efficiencies.
PMID- 29945235
TI - Female-to-Male Gender-Affirming Chest Reconstruction Surgery.
AB - There is an increased demand for gender affirmation surgery. Chest contouring, or
"top" surgery, is especially important in the female-to-male (FtM) transgender
population. This Continuing Medical Education (CME) article critically appraises
the available literature on top surgery to allow plastic surgeons to understand
current practices and determine the best surgical technique using a decision
algorithm and the patient's preoperative anatomy and characteristics. Because a
single best surgical approach does not exist due to significant variance in
preoperative patient anatomy, and in order to provide a useful framework for
decision making, surgical approaches described are categorized as: approach 1
remote incision procedures without skin excision; approach 2-procedures with
periareolar skin excision; and approach 3-mastectomy procedures with skin
excision other than periareolar skin excision. Decision algorithms that help
determine the most suitable surgical technique for individual patients are
reviewed. Data on complication rates and patient satisfaction will improve
informed consent discussions and create realistic patient expectations.
PMID- 29945236
TI - Characterising N-acetylglucosaminylphosphatidylinositol de-N-acetylase (CaGpi12),
the enzyme that catalyses the second step of GPI biosynthesis in Candida
albicans.
AB - Candida albicans N-acetylglucosaminylphosphatidylinositol de-N-acetylase
(CaGpi12) recognises N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) from
Saccharomyces cerevisiae and is able to complement ScGPI12 function. Both N- and
C-terminal ends of CaGpi12 are important for its function. CaGpi12 was
biochemically characterised using rough endoplasmic reticulum microsomes prepared
from BWP17 strain of C. albicans. CaGpi12 is optimally active at 30 degrees C and
pH 7.5. It is a metal-dependent enzyme that is stimulated by divalent cations but
shows no preference for Zn2+ unlike the mammalian homologue. It irreversibly
loses activity upon incubation with a metal chelator. Two conserved motifs, HPDDE
and HXXH, are both important for its function in the cell. CaGPI12 is essential
for growth and viability of C. albicans. Its loss causes reduction of GlcNAc-PI
de-N-acetylase activity, cell wall defects and filamentation defects. The
filamentation defects could be specifically correlated to an upregulation of the
HOG1 pathway.
PMID- 29945237
TI - The Cost-effectiveness of Antimicrobial Lock Solutions for the Prevention of
Central Line-Associated Bloodstream Infections.
AB - Background: Antimicrobial lock solutions are a low-cost strategy that can reduce
the incidence of Central Line-Associated Bloodstream Infections (CLABSI). The aim
of this study was to evaluate the cost-effectiveness of antimicrobial locks for
the prevention of CLABSI. Methods: We constructed a decision-analytic model
comparing antimicrobial lock solutions to heparin locks for the prevention of
CLABSI in three settings: hemodialysis, cancer treatment and home parenteral
nutrition. Cost-effectiveness was determined by calculating CLABSI prevented and
incremental cost-effectiveness ratios (ICER). Uncertainty was addressed by
plotting cost-effectiveness planes and acceptability curves for various
willingness-to-pay thresholds. Results: In probabilistic analysis, at a
willingness-to-pay of $50,000, antimicrobial lock solutions had a 96.24% chance
of being cost-effective compared to heparin locks in the hemodialysis setting, an
88.00% chance in the cancer treatment setting, and a 92.73% chance in the home
parenteral nutrition setting. In base-case analysis, antimicrobial lock solutions
resulted in savings of $68,721.03 for the hemodialysis setting, $85,061.41 for
the cancer setting, and $78,513.83 for the home parenteral nutrition setting per
CLABSI episode prevented. Conclusions: In three distinct and clinically important
settings (hemodialysis, cancer treatment patients and home parenteral nutrition),
antimicrobial lock solutions are an effective strategy for the prevention of
CLABSI and their use can result in significant health-care savings.
PMID- 29945238
TI - Comprehensive molecular classification of localized prostate adenocarcinoma
reveals a tumour subtype predictive of non-aggressive disease.
AB - Background: Management of localized prostate cancer (PCa) is a major clinical
challenge since most of these cancers would not evolve but a majority of patients
will still undergo a life-changing radical surgery. Molecular studies have shown
that PCa can be classified according to their genomic alterations but none of the
published PCa molecular classifications could identify a subtype corresponding to
non-evolutive tumours. Materials and methods: Multi-omics molecular profiling was
carried out on post-radical prostatectomy material from a cohort of 130 patients
with localized PCa. We used unsupervised classification techniques to build a
comprehensive classification of prostate tumours based on three molecular levels:
DNA copy number, DNA methylation, and mRNA expression. Merged data from our
cohort and The Cancer Genome Atlas cohort were used to characterize the resulting
tumour subtypes. We measured subtype-associated risks of biochemical relapse
using Cox regression models and survival data from five cohorts including the two
aforementioned. Results: We describe three PCa molecular subtypes associated with
specific molecular characteristics and different clinical outcomes. Particularly,
one subtype was strongly associated with the absence of biochemical recurrence.
We validated this finding on 746 samples from 5 distinct cohorts (P = 3.41 * 10
8, N = 746 tumour samples), and showed that our subtyping approach outperformed
the most popular prognostic molecular signatures to accurately identify a subset
of patients with a non-evolutive disease. We provide a set of 36 transcriptomic
biomarkers to robustly identify this subtype of non-evolutive cases whose
prevalence was estimated to 22% of all localized PCa tumours. Conclusion: At
least 20% of patients with localized PCa can be accurately predicted to have a
non-evolutive disease on the basis of their molecular subtype. Those patients
should not undergo immediate surgery and rather be placed under active
surveillance.
PMID- 29945239
TI - Growing cell walls show a gradient of elastic strain across their layers.
AB - The relatively thick primary walls of epidermal and collenchyma cells often form
waviness on the surface that faces the protoplast when they are released from the
tensile in-plane stress that operates in situ. This waviness is a manifestation
of buckling that results from the heterogeneity of the elastic strain across the
wall. In this study, this heterogeneity was confirmed by the spontaneous bending
of isolated wall fragments that were initially flat. We combined the empirical
data on the formation of waviness in growing cell walls with computations of the
buckled wall shapes. We chose cylindrical-shaped organs with a high degree of
longitudinal tissue stress because in such organs the surface deformation that
accompanies the removal of the stress is strongly anisotropic and leads to the
formation of waviness in which wrinkles on the inner wall surface are always
transverse to the organ axis. The computations showed that the strain
heterogeneity results from individual or overlaid gradients of pre-stress and
stiffness across the wall. The computed wall shapes depend on the assumed wall
thickness and mechanical gradients. Thus, a quantitative analysis of the wall
waviness that forms after stress removal can be used to assess the mechanical
heterogeneity of the cell wall.
PMID- 29945240
TI - Antibiotics in early life: dysbiosis and the damage done.
AB - Antibiotics are the most common type of medication prescribed to children,
including infants, in the Western world. While use of antibiotics has transformed
previously lethal infections into relatively minor diseases, antibiotic
treatments can have adverse effects as well. It has been shown in children,
adults and animal models that antibiotics dramatically alter the gut microbial
composition. Since the gut microbiota plays crucial roles in immunity, metabolism
and endocrinology, the effects of antibiotics on the microbiota may lead to
further health complications. In this review, we present an overview of the
effects of antibiotics on the microbiome in children, and correlate them to long
lasting complications of obesity, behavior, allergies, autoimmunity and other
diseases.
PMID- 29945241
TI - Histone H2A variants confer specific properties to nucleosomes and impact on
chromatin accessibility.
AB - In eukaryotes, variants of core histone H2A are selectively incorporated in
distinct functional domains of chromatin and are distinguished by conserved
sequences of their C-terminal tail, the L1 loop and the docking domain,
suggesting that each variant confers specific properties to the nucleosome.
Chromatin of flowering plants contains four types of H2A variants, which
biochemical properties have not been characterized. We report that in contrast
with animals, in Arabidopsis thaliana H2A variants define only four major types
of homotypic nucleosomes containing exclusively H2A, H2A.Z, H2A.X or H2A.W. In
vitro assays show that the L1 loop and the docking domain confer distinct
stability of the nucleosome. In vivo and in vitro assays suggest that the L1 loop
and the docking domain cooperate with the C-terminal tail to regulate chromatin
accessibility. Based on these findings we conclude that the type of H2A variant
in the nucleosome impacts on its interaction with DNA and propose that H2A
variants regulate the dynamics of chromatin accessibility. In plants, the
predominance of homotypic nucleosomes with specific physical properties and their
specific localization to distinct domains suggest that H2A variants play a
dominant role in chromatin dynamics and function.
PMID- 29945243
TI - A role for beta,beta-xanthophylls in Arabidopsis UV-B photoprotection.
AB - Plastidial isoprenoids, such as carotenoids and tocopherols, are important anti
oxidant metabolites synthesized in plastids from precursors generated by the
methylerythritol 4-phosphate (MEP) pathway. In this study, we found that
irradiation of Arabidopsis thaliana plants with UV-B caused a strong increase in
the accumulation of the photoprotective xanthophyll zeaxanthin but also resulted
in slightly higher levels of gamma-tocopherol. Plants deficient in the MEP
enzymes 1-deoxy-D-xylulose 5-phosphate synthase and 1-hydroxy-2-methyl-2-butenyl
4-diphosphate synthase showed a general reduction in both carotenoids and
tocopherols and this was associated with increased DNA damage and decreased
photosynthesis after exposure to UV-B. Genetic blockage of tocopherol
biosynthesis did not affect DNA damage accumulation. In contrast, lut2 mutants
that accumulate beta,beta-xanthophylls showed decreased DNA damage when
irradiated with UV-B. Analysis of aba2 mutants showed that UV-B protection was
not mediated by ABA (a hormone derived from beta,beta-xanthophylls). Plants
accumulating beta,beta-xanthophylls also showed decreased oxidative damage and
increased expression of DNA-repair enzymes, suggesting that this may be a
mechanism for these plants to decrease DNA damage. In addition, in vitro
experiments also provided evidence that beta,beta-xanthophylls can directly
protect against DNA damage by absorbing radiation. Together, our results suggest
that xanthophyll-cycle carotenoids that protect against excess illumination may
also contribute to protection against UV-B.
PMID- 29945244
TI - The assessment of changes to the nontuberculous mycobacterial metabolome in
response to anti-TB drugs.
AB - Mycobacterium species can cause a range of nontuberculous infections of healthy
and immunocompromised people as well as infected people during and after surgical
procedures. The similarity of nontuberculous mycobacteria (NTM) to the
tuberculosis bacilli (TB) could ultimately enable the use of anti-TB drugs for
the genus. Hence, three NTM (Mycobacterium smegmatis, Mycobacterium phlei and
Mycobacterium avium) were cultured under different lab conditions, causing two
mycobacterial phenotypes (active and dormant), and treated with isoniazid (INH)
and ethambutol (EMB) independently or in combination. Metabolite profiling was
applied to facilitate the investigation and characterisation of intracellular
targets affected by the antibiotics. Aliquots of the cell culture were taken over
the treatment period and the metabolite profile of the cells analysed by gas
chromatography mass spectrometry. Comparative analysis of the metabolite levels
to untreated mycobacteria confirmed the successful action of the antibiotics on
the metabolism of all three species. Furthermore, single metabolites and
metabolite pathways affected by the antibiotics could be identified and included,
besides the known target sites for INH and EMB on mycobacterial cells, changes in
e.g. nucleotide and saccharide levels. The combined treatment highlighted the
property of EMB to enhance the effects of INH even under hypoxic culture
conditions.
PMID- 29945245
TI - Neural Tension Technique Improves Immediate Conditioned Pain Modulation in
Patients with Chronic Neck Pain: A Randomized Clinical Trial.
AB - Objective: To determine the immediate effect of neural tension technique (NTT) on
conditioned pain modulation in patients with chronic neck pain. A secondary
objective was to determine the immediate effect of neural tensioner technique on
pain intensity and cervical range of movement. Design: Randomized clinical trial.
Setting: University medical center. Subjects: Fifty-four patients with neck pain
(13 males and 41 females; mean+/- SD age = 20.91 +/- 2.64 years) were randomly
allocated to two groups: NTT or sham technique. Methods: Participants received a
visual analog scale (VAS) and neck disability index (NDI) after inclusion.
Conditioned pain modulation (CPM) and active cervical range of motion were
measured before and after the intervention. Each subject received one treatment
session. Results: The results of the analysis of variance revealed a significant
effect for the group * time interaction only for CPM (F = 11.09, P = 0.002, etap2
= 0.176). No significant interactions were found for the other measures (VAS [F =
1.719, P = 0.195, etap2 = 0.031], pressure pain threshold C2 [F = 0.731, P =
0.398, etap2 = 0.018], flexion [F = 0.176, P = 0.677, etap2 = 0.003], extension
[F = 0.035, P = 0.852, etap2 = 0.001], lateral flexions [F = 0.422, P = 0.519,
etap2 = 0.008], and rotations [F = 1.307 P = 0.258, etap2 = 0.024]). Regarding
CPM, intergroup interaction differences were found postintervention (P = 0.002)
with a high effect size (d = 0.98). Conclusions: This study suggests that neural
tension technique enhances immediate conditioned pain modulation in patients with
chronic neck pain, but not pain intensity or cervical range of movement.
PMID- 29945242
TI - Mitochondrial Dysfunction and Infection Generate Immunity-Fecundity Tradeoffs in
Drosophila.
AB - Physiological responses to short-term environmental stressors, such as infection,
can have long-term consequences for fitness, particularly if the responses are
inappropriate or nutrient resources are limited. Genetic variation affecting
energy acquisition, storage, and usage can limit cellular energy availability and
may influence resource-allocation tradeoffs even when environmental nutrients are
plentiful. Here, we utilized Drosophila mitochondrial-nuclear genotypes to test
whether disrupted mitochondrial function interferes with nutrient-sensing
pathways, and whether this disruption has consequences for tradeoffs between
immunity and fecundity. We found that an energetically-compromised genotype was
relatively resistant to rapamycin-a drug that targets nutrient-sensing pathways
and mimics resource limitation. Dietary resource limitation decreased survival of
energetically-compromised flies. Furthermore, survival of infection with a
natural pathogen was decreased in this genotype, and females of this genotype
experienced immunity-fecundity tradeoffs that were not evident in genotypic
controls with normal energy metabolism. Together, these results suggest that this
genotype may have little excess energetic capacity and fewer cellular nutrients,
even when environmental nutrients are not limiting. Genetic variation in energy
metabolism may therefore act to limit the resources available for allocation to
life-history traits in ways that generate tradeoffs even when environmental
resources are not limiting.
PMID- 29945246
TI - Cell wall extensins in root-microbe interactions and root secretions.
AB - Extensins are cell wall glycoproteins, belonging to the hydroxyproline-rich
glycoprotein (HRGP) family, which are involved in many biological functions,
including plant growth and defence. Several reviews have described the
involvement of HRGPs in plant immunity but little focus has been given
specifically to cell wall extensins. Yet, a large set of recently published data
indicates that extensins play an important role in plant protection, especially
in root-microbe interactions. Here, we summarise the current knowledge on this
topic and discuss the importance of extensins in root defence. We first provide
an overview of the distribution of extensin epitopes recognised by different
monoclonal antibodies among plants and discuss the relevance of some of these
epitopes as markers of the root defence response. We also highlight the
implication of extensins in different types of plant interactions elicited by
either pathogenic or beneficial micro-organisms. We then present and discuss the
specific importance of extensins in root secretions, as these glycoproteins are
not only found in the cell walls but are also released into the root mucilage.
Finally, we propose a model to illustrate the impact of cell wall extensin on
root secretions.
PMID- 29945248
TI - Effects of the Mitochondrial and Nuclear Genomes on Nonshivering Thermogenesis in
a Wild Derived Rodent.
AB - A key adaptation of mammals to their environment is their ability to maintain a
constant high body temperature, even at rest, under a wide range of ambient
temperatures. In cold climates, this is achieved by an adaptive production of
endogenous heat, known as nonshivering thermogenesis (NST), in the brown adipose
tissue (BAT). This organ, unique to mammals, contains a very high density of
mitochondria, and BAT correct functioning relies on the correct functioning of
its mitochondria. Mitochondria enclose proteins encoded both in the maternally
inherited mitochondrial genome and in the biparentally inherited nuclear genome,
and one overlooked hypothesis is that both genomes and their interaction may
shape NST. By housing under standardized conditions wild-derived common voles
(Microtus arvalis) from two distinct evolutionary lineages (Western [W] and
Central [C]), we show that W voles had greater NST than C voles. By introgressing
those two lineages over at least nine generations, we then experimentally tested
the influence of the nuclear and mitochondrial genomes on NST and related
phenotypic traits. We found that between-lineage variation in NST and BAT size
were significantly influenced by the mitochondrial and nuclear genomes,
respectively, with the W mitochondrial genotype being associated with higher NST
and the W nuclear genotype with a larger BAT. There were significant mito-nuclear
interactions on whole animal body weight and resting metabolic rate (RMR). Hybrid
voles were lighter and had higher RMR. Overall, our findings turn new light on
the influence of the mitochondrial and nuclear genomes on thermogenesis and
building adaptation to the environment in mammals.
PMID- 29945247
TI - Trisomy of human chromosome 21 enhances amyloid-beta deposition independently of
an extra copy of APP.
AB - Down syndrome, caused by trisomy of chromosome 21, is the single most common risk
factor for early-onset Alzheimer's disease. Worldwide approximately 6 million
people have Down syndrome, and all these individuals will develop the hallmark
amyloid plaques and neurofibrillary tangles of Alzheimer's disease by the age of
40 and the vast majority will go on to develop dementia. Triplication of APP, a
gene on chromosome 21, is sufficient to cause early-onset Alzheimer's disease in
the absence of Down syndrome. However, whether triplication of other chromosome
21 genes influences disease pathogenesis in the context of Down syndrome is
unclear. Here we show, in a mouse model, that triplication of chromosome 21 genes
other than APP increases amyloid-beta aggregation, deposition of amyloid-beta
plaques and worsens associated cognitive deficits. This indicates that
triplication of chromosome 21 genes other than APP is likely to have an important
role to play in Alzheimer's disease pathogenesis in individuals who have Down
syndrome. We go on to show that the effect of trisomy of chromosome 21 on amyloid
beta aggregation correlates with an unexpected shift in soluble amyloid-beta
40/42 ratio. This alteration in amyloid-beta isoform ratio occurs independently
of a change in the carboxypeptidase activity of the gamma-secretase complex,
which cleaves the peptide from APP, or the rate of extracellular clearance of
amyloid-beta. These new mechanistic insights into the role of triplication of
genes on chromosome 21, other than APP, in the development of Alzheimer's disease
in individuals who have Down syndrome may have implications for the treatment of
this common cause of neurodegeneration.
PMID- 29945250
TI - Phoresy and Within-colony Transmission of Nematodes Associated with Alates of
Subterranean Termites (Isoptera: Rhinotermitidae).
AB - Termites and their nests are potential resources for a wide assemblage of taxa
including nematodes. During dispersal flight events from termite colonies, co
occurring nematodes in the nest may have phoretic opportunities to use termite
alates as transportation hosts. The two subterranean termite species Coptotermes
gestroi (Wasmann) and Coptotermes formosanus Shiraki are both invasive and
established in south Florida. Alates of both species (n = 245) were collected
during dispersal flight events in 2015-2016 from six locations, of which 30
(12.2%) were associated with one or more species of nematodes. Species of
Bunonema Jagerskiold (Rhabditida: Bunonematidae), Halicephalobus Timm (Rhabditda:
Panagrolaimidae), and Poikilolaimus regenfussi (Sudhaus) Sudhaus and Koch
(Rhabditida: Rhabditidae) were isolated from 5.3, 4.9, and 0.4% of termite
alates, respectively, and Bunonema and Halicephalobus were concomitant in 1.6% of
alates. Additional C. formosanus alates were field-collected to establish
laboratory colonies in sterilized rearing containers (SRC) to determine if alate
associated nematodes would colonize the newly established nest and/or brood.
Among 1-yr-old termite colonies reared in SRCs, 26.9% of the colonies were
positive for nematodes confirming that within-colony transmission of nematodes
occurred. All three isolated nematode genera are free-living bacterivores capable
of asexual reproduction. This suggests that these common co-occurring, termite
associated nematodes are opportunistic and facultative symbionts that receive
increased opportunities of geographical dispersion through phoresy during termite
dispersal flight events.
PMID- 29945249
TI - Convergent evolution of integration site selection upstream of tRNA genes by
yeast and amoeba retrotransposons.
AB - Transposable elements amplify in genomes as selfish DNA elements and challenge
host fitness because their intrinsic integration steps during mobilization can
compromise genome integrity. In gene-dense genomes, transposable elements are
notably under selection to avoid insertional mutagenesis of host protein-coding
genes. We describe an example of convergent evolution in the distantly related
amoebozoan Dictyostelium discoideum and the yeast Saccharomyces cerevisiae, in
which the D. discoideum retrotransposon DGLT-A and the yeast Ty3 element
developed different mechanisms to facilitate position-specific integration at
similar sites upstream of tRNA genes. Transcription of tRNA genes by RNA
polymerase III requires the transcription factor complexes TFIIIB and TFIIIC.
Whereas Ty3 recognizes tRNA genes mainly through interactions of its integrase
with TFIIIB subunits, the DGLT-A-encoded ribonuclease H contacts TFIIIC subunit
Tfc4 at an interface that covers tetratricopeptide repeats (TPRs) 7 and 8. A
major function of this interface is to connect TFIIIC subcomplexes tauA and tauB
and to facilitate TFIIIB assembly. During the initiation of tRNA gene
transcription tauB is displaced from tauA, which transiently exposes the TPR 7/8
surface of Tfc4 on tauA. We propose that the DGLT-A intasome uses this binding
site to obtain access to genomic DNA for integration during tRNA gene
transcription.
PMID- 29945251
TI - Impact of transmitted HIV-1 drug resistance on the efficacy of first-line
antiretroviral therapy with two nucleos(t)ide reverse transcriptase inhibitors
plus an integrase inhibitor or a protease inhibitor.
AB - Objectives: To examine the impact of transmitted drug resistance (TDR) on
response to first-line regimens with integrase strand transfer inhibitors
(INSTIs) or boosted protease inhibitors (bPIs). Methods: From an Italian
observational database (ARCA) we selected HIV-1-infected drug-naive patients
starting two NRTIs and either an INSTI or a bPI, with an available pre-ART
resistance genotype. The endpoint was virological failure (VF; plasma HIV-1 RNA
>200 copies/mL after week 24). WHO surveillance drug resistance mutations and the
Stanford algorithm were used to classify patients into three resistance
categories: no TDR (A), TDR but fully-active ART prescribed (B), TDR and at least
low-level resistance to one or more prescribed drug (C). Results: We included
1365 patients with a median follow-up of 96 weeks (IQR 54-110): 1205 (88.3%)
starting bPI and 160 (11.7%) INSTI. Prevalence of TDR was 6.1%, 12.5%, 2.6% and
0% for NRTI, NNRTI, bPI and INSTI, respectively. Cumulative Kaplan-Meier
estimates for VF at 48 weeks were 11% (95% CI 10.1%-11.9%) for the bPI group and
7.7% (95% CI 5.4%-10%) for the INSTI group. In the INSTI group, cumulative
estimates for VF at 48 weeks were 6% (95% CI 4%-8%) in resistance category A, 5%
(95% CI 1%-10%) in B and 50% (95% CI 30%-70%) in C (P < 0.001). Resistance
category C [versus A, adjusted hazard ratio (aHR) 12.6, 95% CI 3.2-49.8, P <
0.001] and nadir CD4 (+100 cells/mm3, aHR 0.6, 95% CI 0.4-0.9, P = 0.03)
predicted VF. In the bPI group, VF rates were not influenced by baseline
resistance. Conclusions: Our data support the need for NRTI resistance genotyping
in patients starting an INSTI-based first-line ART.
PMID- 29945252
TI - Short Course High-dose Liposomal Amphotericin B for HIV-associated Cryptococcal
Meningitis: A phase-II Randomized Controlled Trial.
AB - Background: Cryptococcal meningitis (CM) causes 10-20% of HIV-related deaths in
Africa. We performed a phase-II non-inferiority trial examining the Early
Fungicidal Activity (EFA) of three short-course, high-dose liposomal amphotericin
B (L-AmB) regimens for CM in Tanzania and Botswana. Method: HIV-infected adults
with CM were randomized to: (i) L-AmB 10mg/kg day 1 (single dose); (ii) L-AmB
10mg/kg day 1, 5mg/kg day 3 (two doses); (iii) L-AmB 10mg/kg day 1, 5 mg/kg days
3 and 7 (three doses); (iv) standard 14-day L-AmB 3mg/kg/day (control); all given
with fluconazole 1200mg/day for 14 days. Primary endpoint was mean rate of
clearance of cerebrospinal fluid (CSF) cryptococal infection (EFA). Non
inferiority was defined as an upper limit of the two-sided 95% confidence
interval (CI) of difference in EFA between intervention and control less than 0.2
log10CFU/ml/day. Results: 80 participants were enrolled. EFA for daily L-AmB was
0.41 (standard deviation 0.11, n=17) log10CFU/mL/day. Difference in mean EFA from
control was -0.11 (95%CI -0.29,0.07) log10CFU/mL/day faster with single dose
(n=16); -0.05 (95%CI -0.20,0.10) log10CFU/mL/day faster with two doses (n=18);
and -0.13 (95%CI -0.35,0.09) log10CFU/mL/day faster with three doses (n=18). EFA
in all short-course arms was non-inferior to control at the predefined non
inferiority margin. Overall 10-week mortality was 29% (n=23) with no statistical
difference between arms. All arms were well tolerated. Conclusions: Single dose
10mg/kg L-AmB was well tolerated and led to non-inferior EFA compared to 14 days
of 3mg/kg/d L-AmB in HIV-associated CM. Induction based on single 10mg/kg L-AmB
dose is being taken forward to a phase-III clinical endpoint trial.
PMID- 29945253
TI - Molecular cloning, characterization, and functional analysis of pigeon (Columba
livia) Toll-like receptor 5.
AB - Toll-like receptors (TLRs) are pattern recognition receptors that are vital for
the recognition of pathogen-associated molecular patterns. TLR5 is responsible
for the recognition of bacterial flagellin to induce the NF-kappaB activation and
innate immune responses. In this study, we cloned and identified the TLR5 gene
from the King pigeon (Columba livia) designated as PiTLR5. Full-length PiTLR5
cDNA (2583 bp) encoded an 860-amino acid protein containing a signal peptide
sequence, 10 leucine-rich repeat domains, a leucine-rich repeat C-terminal
domain, a transmembrane domain, and an intracellular Toll-interleukin-1 receptor
domain. Pigeon TLR5 mRNA expression was quantified by performing quantitative
real-time PCR (qRT-PCR), which showed that PiTLR5 was broadly expressed in all
examined tissues, with the highest expression in the liver, peripheral blood
mononuclear cells, and spleen. PiTLR5-mediated innate immune responses were
measured by determining its effects on NF-kappaB activation and cytokine
expression. The results showed that HEK293T cells transfected with PiTLR5
robustly activated the NF-kappaB response to flagellin, but not other TLR
stimuli, and induced significant upregulation of IL-1beta, IL-8, TNF-alpha, and
IFN-gamma, indicating that PiTLR5 is a functional TLR5 homolog. Additionally,
following flagellin stimulation of pigeon splenic lymphocytes, the levels of
TLR5, NF-kappaB, IL-6, IL-8, CCL5, and IFN-gamma mRNA, assessed using qRT-PCR,
were significantly upregulated. Besides, TLR5 knockdown resulted in the
significantly downregulated expression of NF-kappaB and related
cytokines/chemokines. Triggering pigeon TLR5 contributes to significant
upregulation of inflammatory cytokines and chemokines, suggesting that pigeon
TLR5 plays an important role in the innate immune responses.
PMID- 29945254
TI - Atrioventricular valve replacement in single-ventricle circulation: a viable
option?
PMID- 29945255
TI - Expression and effect of Calpain9 gene genetic polymorphism on slaughter
indicators and intramuscular fat content in chickens.
AB - Calpain 9 (CAPN9) is expressed in the stomach and small intestine. CAPN9 has
regulatory roles in hypertension, heart disease, gastric mucosal defense, and
kidney disease. The involvement of CAPN9 has not been reported in the development
of chickens. CAPN9 mRNA was found in adipose and muscle tissue in this study. Two
linkage single nucleotide polymorphisms (SNP; G7518A and C7542G) in intron 4 were
screened from 160 birds of the D2 chicken line. The 2 mutation sites were
associated with carcass weight, evisceration weight, abdominal fat weight (AFW),
abdominal fat percentage (AFP), and breast muscle percentage (all P < 0.05).
Intramuscular fat (IMF) content was not significantly different in the 3
genotypes. But, the AA(7518)/GG(7542) genotype had the highest IMF content,
highest breast muscle weight, and lower AFW and AFP. Moreover, the mRNA level of
CAPN9 in abdominal fat tissue was significantly different (P < 0.05 or P < 0.01)
between any 2 genotypes, consistent with AFW and AFP. In summary, the expression
of CAPN9 in adipose and breast muscle tissue is reported for the first time.
CAPN9 affected production performance of chickens. As a marker, the linkage
G7518A and C7542G polymorphisms in intron 4 of CAPN9 could affect the production
traits by regulating mRNA expression. The findings concerning the marker enrich
the theoretical foundation for molecular breeding of high-quality broilers.
PMID- 29945256
TI - A structural equation model of the family physicians attitude towards their role
in prevention: a cross-sectional study in Switzerland.
AB - Background: In contrast to many studies exploring barriers to preventive care in
family medicine, there is less quantitative research regarding the self-perceived
role of family physicians (FPs) in prevention and its predictive factors.
Moreover, the existing studies considered this attitude as a homogeneous entity.
The objective of this study is firstly, to characterize FPs' attitudes towards
prevention taking into account nine different prevention themes, and secondly, to
explore the factors that could be predictive of this attitude. Methods: The data
stem from a cross-sectional national survey on prevention we conducted in
Switzerland from 2015 to 2016 (170 physicians randomly drawn, online
questionnaire). We first performed a confirmatory factor analysis to define a
homogeneous latent variable regarding physicians' attitude towards prevention,
then, a structural equation modeling to identify potential predictors. Results:
The FP' attitude towards their role in preventive care was homogeneously positive
whatever the topic (smoking, drinking dietary habits, physical activities, and
more generally, cardiovascular risk factors) except for occupational risks and
cannabis consumption. A feeling of good effectiveness was a positive predictor of
this positive attitude while seniority, the lack of reimbursement and being a
physician from the German-speaking area were negative predictors. Conclusion: The
FP' attitude about their role in prevention is homogeneous concerning the
'classical' topics of prevention, whereas they still under-recognize certain
topics as important fields for prevention. To change this situation, we probably
need a global effort to introduce other ways of thinking about prevention,
including not only FP but also all stakeholders.
PMID- 29945257
TI - A New Injury Prevention Target: Summer Hair Braids.
AB - Scald injuries caused by hair braiding have become increasingly common in our
pediatric burn center's African-American population. This injury mechanism has
received little attention in the medical literature. To guide prevention, the
present study aims to characterize this novel mechanism of injury and identify
patterns underlying its frequency. A retrospective cohort analysis was performed
on all cases of scald injury due to hair braiding in African-American girls
treated at our burn center from 2000 to 2016. Data were gathered from the
patient's medical records to determine demographics, details of the injury, and
treatment rendered. Patterns of injury frequency were identified and
statistically analyzed. Thirty-four patients suffered scald injuries associated
with hair braiding. The mean patient age was 8.4 years (SD +/- 5 years). The
majority of injuries (90%) occurred in the home. The frequency of injuries
significantly increased starting in the year 2012, rising from less than 3% to
more than 10% of evaluated injuries in African-American girls (P = .0015).
Injuries were significantly more frequent in summer months. Injuries resulted in
considerable usage of medical resources, including ambulance transport, hospital
admission, clinic visits, prolonged wound care, and surgery. Complications
developed in 41% of injured children; the most frequent complication was
scarring. Pediatric scald injuries caused by braiding practices are morbid, have
recently become increasingly frequent, tend to occur in the summer, and may be
related to a new do-it-yourself style trend among African-American girls.
PMID- 29945258
TI - Scrotal calcinosis in an adult patient with amyopathic dermatomyositis.
PMID- 29945259
TI - A proprietary herbal extract against hair loss in androgenetic alopecia and
telogen effluvium: a placebo-controlled, single-blind, clinical-instrumental
study.
AB - INTRODUCTION: Currently there are only a limited number of drugs available for
treatment of androgenetic alopecia and telogen effluvium. However, certain plants
and their standardized extracts may provide some clinical benefits against hair
loss. We formulated a herbal shampoo and a solution to evaluate their efficacy,
safety, and synergy in hair loss. METHODS: We conducted a randomized, placebo
controlled, single-blind, clinical and instrumental study for 6 months on 120
subjects with androgenetic alopecia and telogen effluvium, confirmed by pull test
and phototricogram. Each subject was examined monthly. At the end of the study, a
self-assessment test was carried out. RESULTS: Herbal formulations were found to
be more effective in preventing and reducing hair loss than placebo at every
assessment point. Anagen/telogen ratios improved significantly in the study
group. In addition, concomitant use of the shampoo and solution were found to be
more effective than single product use. CONCLUSION: We interpret this eutrophic
effect for scalp hair as the final outcome of the entire content of our herbal
formula, which has antiandrogenic, anti-inflammatory, antioxidative, angiogenic,
and hair-stimulating features. In combination, these features help prevent hair
from falling out and reducing hair loss.
PMID- 29945260
TI - Human papillomavirus (HPV) infection and vaccination: knowledge and attitudes
among healthcare professionals and the general public in Slovenia.
AB - INTRODUCTION: This study evaluates knowledge of and attitudes toward human
papillomavirus (HPV) infection and vaccination among healthcare professionals and
the general public in Slovenia. METHODS: Five statements were designed to
evaluate participants' opinions regarding age at HPV vaccine administration and
potential delay in vaccination, associations of HPV vaccination with riskier
sexual behavior, HPV vaccine safety, the importance of the internet as a source
of information, and the significance of HPV vaccination in boys. Participants
were asked to express agreement or disagreement with each statement. RESULTS: A
total of 605 surveys were completed by medical students (n = 259), parents of
sixth-graders in 2016 (n = 103) and 2017 (n = 103), pediatricians and school
medicine specialists (n = 21), gynecologists (n = 34), and women visiting
gynecology outpatient clinics (n = 85). The highest level of knowledge and belief
in the HPV vaccine and its safety was observed among pediatricians and school
medicine specialists. Medical students tend to have a very positive attitude
toward HPV vaccination, although they need additional education about HPV vaccine
safety. Some healthcare professionals showed signs of HPV vaccine hesitancy, and
their beliefs were somewhat similar to those of the general public. CONCLUSIONS:
Although the overall attitude towards HPV vaccination is generally positive,
additional education must be provided to both healthcare professionals and the
general public in order to achieve higher HPV vaccination coverage rates in
Slovenia.
PMID- 29945261
TI - Malassezia infection associated with chronic spontaneous urticaria without
angioedema: a report on five cases.
AB - INTRODUCTION: Chronic spontaneous urticaria (CSU) is a challenging condition to
treat and it significantly affects quality of life. Bacterial, viral, parasitic,
and fungal infections have been associated with triggering and/or perpetuating
urticaria in certain individuals. There is a paucity of literature on CSU
associated with Malassezia infection. METHODS AND RESULTS: We present a case
series of five patients with CSU without angioedema in whom we observed temporal
association of Malassezia infection with CSU. The presence of Malassezia was
confirmed by clinical examination, Wood's lamp, and KOH examination. The patients
with CSU experienced improvement after specific antifungal therapy. CONCLUSIONS:
Malassezia infection may be associated with recurrent and chronic urticaria in a
certain group of susceptible patients and thus specific targeted therapy against
it might result in complete remission of urticaria along with clearing of the
infection.
PMID- 29945262
TI - Four-point injection technique for lip augmentation.
AB - INTRODUCTION: Lip augmentation procedures with hyaluronic acid dermal fillers
have become increasingly popular worldwide because full lips are often considered
beautiful and youthful. The goal of a lip augmentation procedure is to create
smooth lips with adequate volume and a natural appearance. Various techniques for
lip augmentation have been utilized and described. METHODS: In the four-point
injection technique, the lips were divided equally into right side and left side.
Four entry points were made above the vermilion border for the upper lip and
below the vermilion border for the lower lip. The filler was administered with a
fanning technique through each entry point. RESULTS: Between January 2017 and
November 2017, 50 female patients underwent a nonsurgical lip augmentation
procedure with injectable fillers using this technique. Forty-five patients (90%)
reported that they were satisfied or extremely satisfied with their lip
enhancement procedure. No serious complications were observed. CONCLUSION: The
advantages of this technique are reducing the risk of complications like
erythema, edema, and vascular injuries, and providing easy access to injection
sites.
PMID- 29945263
TI - Comparing the diagnostic properties of skin scraping, adhesive tape, and
dermoscopy in diagnosing scabies.
AB - INTRODUCTION: Scabies is a contagious skin infestation that mainly presents with
itching at night and skin burrows that are visible to the naked eye. Diagnosing
scabies with dermoscopy is still a matter of controversy. The aim of our study
was to compare the diagnostic properties of adhesive tape, skin scraping, and
dermoscopy in diagnosing scabies. METHODS: One hundred patients with clinical
presumptive diagnoses of scabies underwent skin scraping, adhesive tape testing,
and dermoscopic examination. Each diagnostic procedure was performed on three
different areas. RESULTS: Comparing the diagnostic properties of the three
methods, the adhesive tape test was the most sensitive method for diagnosing
scabies. Sixteen cases (16.0%) were definitely diagnosed as scabies using the
adhesive tape test detecting the presence of mites or their eggs. Only 10 cases
(10.0%) were definitely diagnosed as scabies using the skin scraping test
detecting mites or their eggs. Dermoscopic examination suggested a diagnosis of
scabies in 22 cases (22.0%), of which only 10 were definitely diagnosed as
scabies by detecting mites using the adhesive tape test, skin scraping, or both.
CONCLUSION: The diagnosis of scabies can only be confirmed by seeing mites. The
adhesive tape test and skin scraping procedure have high specificity in
diagnosing scabies, but their low sensitivity cannot exclude the possibility of
scabies. Dermoscopy-guided tape testing can be a helpful tool for better
diagnosis of scabies.
PMID- 29945264
TI - Store-and-forward teledermatology for the most common skin neoplasms in Ukraine.
AB - BACKGROUND: Among all malignancies in Ukraine in 2016, the group of non-melanoma
skin cancers headed the list in men and made up 21.6%. This group was second in
women and made up 17.6%. The diagnostics of skin tumors are becoming increasingly
relevant. METHODS: The store-and-forward (SAF) method was used. The study
included patients that were remotely diagnosed with melanocytic nevi, seborrheic
keratoses, skin cancer, and skin melanoma. Patients signed up for remote
diagnostics, were examined in person by dermatologists, and had tumors excised
with a subsequent histological examination. RESULTS: Using telemedicine, 108
melanocytic nevi, 97 seborrheic keratoses, 62 skin cancers, and 47 skin melanomas
were diagnosed and selected. The accuracy of teledermatological examination and
teledermoscopy compared to clinical examination and dermoscopy was 90.3 to
100.0%. The accuracy of teledermatological examination and teledermoscopy
compared to histopathological diagnoses was 85.1 to 98.9%. CONCLUSIONS:
Teledermatological diagnosis showed a high ability for detecting skin neoplasms
in Ukraine.
PMID- 29945265
TI - Hematidrosis (bloody sweat): a review of the recent literature (1996-2016).
AB - Hematidrosis is an eccrine sweat disorder characterized by one or more episodes
of spontaneous, bloody sweating from non-traumatized skin. The author carried out
a systematic review of all cases of hematidrosis reported in PubMed over the past
20 years. A total of 25 cases were reviewed; 21 were women (84%), the median age
was 13 years (range 9-72), and the majority (62%) were from Asia, mainly India.
Hematidrosis was located on the face-including the forehead (40%), eyes (40%),
and ears (36%)-in 96% of the cases and on the umbilicus in 24% and the palms in
20%. Prodromal symptoms were reported by almost 30% of the patients. Possible
triggering factors were identified in 56% of the cases; most of these (86%) were
stress factors within families (conflicts or abuse) or at school. In two cases,
platelet dysfunction and epilepsy were suspected as culprits. Nine patients had a
psychiatric diagnosis associated with hematidrosis. The outcome was favorable in
most of the cases with medical treatment (e.g., beta-blocker, anxiolytics) and
psychological support. The number of cases has increased in recent years.
Hematidrosis appears to be a somatization disorder that mainly affects children
from developing countries. Its physiopathology remains largely unknown. It
deserves better recognition because it is usually a temporary condition when
managed properly.
PMID- 29945267
TI - Cupping in dermatology: a critical review and update.
AB - Cupping is an ancient procedure that has been practiced for thousands of years.
It has been used to treat a variety of medical conditions, including
dermatological ones. Cupping has been described in the literature for the
treatment of conditions such as acne and eczema. The procedure is fundamentally
divided into dry cupping and wet cupping; however, there have been many modern
adaptations. Adverse events related to the procedure have been reported in the
literature and should be considered by patients. However, cupping has a promising
role in helping manage dermatological conditions.
PMID- 29945266
TI - Interleukin-2 and other cytokines in candidiasis: expression, clinical
significance, and future therapeutic targets.
AB - Susceptibility to Candida spp. infection is largely determined by the status of
host immunity, whether immunocompromised/immunodeficient or immunocompetent.
Interleukin-2 (IL-2), a potent lymphoid cell growth factor, is a four-alpha-helix
bundle cytokine induced by activated T cells with two important roles: the
activation and maintenance of immune responses, and lymphocyte production and
differentiation. We reviewed the roles of cytokines as immune stimulators and
suppressors of Candida spp. infections as an update on this continuously evolving
field. We performed a comprehensive search of the Cochrane Central Register of
Controlled Trials, Medline (PubMed), and Embase databases for articles published
from March 2010 to March 2016 using the following search terms: interleukins,
interleukin-2, Candida spp., and immunosuppression. Data from our own studies
were also reviewed. Here, we provide an overview focusing on the ability of IL-2
to induce a large panel of trafficking receptors in skin inflammation and control
T helper (Th)2 cytokine production in response to contact with Candida spp.
Immunocompromised patients have reduced capacity to secrete Th1-related cytokines
such as IL-2. The ability to secrete the Th1-related cytokine IL-2 is low in
immunocompromised patients. This prevents an efficient Th1 immune response to
Candida spp. antigens, making immunocompromised patients more susceptible to
candidal infections.
PMID- 29945268
TI - Dermatitis neglecta: a challenging diagnosis in psychodermatology.
AB - Dermatitis neglecta is a condition affecting the skin caused by a lack of
hygiene. It may be related to psychiatric and neurological disturbances. The
appearance of skin lesions results from neglect, which helps distinguish this
condition from other similar clinical entities. Resolution of the lesions with
adequate cleansing aids a definitive diagnosis.
PMID- 29945269
TI - Concomitant morphea and lichen sclerosus et atrophicus in the same plaque at the
site of intramuscular drug injection: an interesting case presentation.
AB - Morphea and lichen sclerosus et atrophicus (LSA) are two diseases that show
considerable clinical and histopathological similarity and have been known to
coexist in the same patient. Whether the two conditions are different entities or
part of the same spectrum has been a topic of debate. This article describes a
very rare and interesting case of concomitant morphea and LSA in a 50-year-old
female in the same plaque following intramuscular drug injection in the deltoid
region of the right arm. The coexistence of morphea and LSA in the same lesion
has rarely been reported, thus compelling us to report this case.
PMID- 29945270
TI - The Association Between the Levels of Thyroid Hormones and Peripheral Nerve
Conduction in Patients with Type 2 Diabetes Mellitus.
AB - BACKGROUND: Type 2 diabetes has an underlying pathology with thyroid dysfunction.
However, few studies have investigated the association between thyroid hormones
and diabetic peripheral neuropathy. Our aim was to evaluate the relationship
between thyroid hormones and electrophysiological properties of peripheral nerves
in type 2 diabetes. PATIENTS AND METHODS: The medical records of 308 patients
with type 2 diabetes were enrolled in this study. Subjects stratified by sex were
divided into subgroups based on the diagnosis of nerve conduction study. The
nerve conduction parameters were separately described with the spectrum of
thyroid hormones. Multivariate regression models to analyze the potential links
between thyroid hormones and nerve conduction parameters. RESULTS: The serum free
triiodine thyronine levels between normal and abnormal nerve conduction groups
were statistically different in total (4.55+/-0.65 vs 4.37+/-0.63, P<0.05) and
female diabetic patients (4.46+/-0.50 vs 4.14+/-0.57, P<0.01). Moreover, the
summed amplitude and velocity Z score of female and male increased with free
triiodine thyronine levels (P<0.05). Sex-specific binary logistic regression
models showed that free triiodine thyronine levels were associated with decreased
odds of abnormal nerve conduction diagnosis (odds ratio [95%CI]=0.151[0.047
0.186]) and low tertile of summed amplitude Z score (odds ratio
[95%CI]=0.283[0.099-0.809]) in female. In total patients, free triiodine
thyronine level was negatively associated with odds of abnormal nerve conduction
(odds ratio [95%CI]=0.436 [0.226-0.842]), low tertile of summed velocity (odds
ratio [95%CI]=0.44[0.226-0.858]) and amplitude (odds ratio [95%CI]=0.436[0.227
0.838) Z score. CONCLUSIONS: Serum free triiodine thyronine level is associated
with nerve conduction in diabetes. Low free triiodine thyronine may be a
potential risk for diabetic peripheral neuropathy.
PMID- 29945271
TI - Training Performed Above Lactate Threshold Decreases p53 and Shelterin Expression
in Mice.
AB - Telomere shortening is associated to sarcopenia leading to functional impairment
during aging. There are mechanisms associated with telomere attrition, as well to
its protection and repair. Physical training is a factor that attenuates telomere
shortening, but little is known about the effects of different exercise
intensities on telomere biology. Thus, we evaluated the effects of exercise
intensity (moderate vs. high-intensity domain) on gene expression of senescence
markers Checkpoint kinase 2 and tumor suppressor (Chk2 and p53, respectively),
shelterin telomere repeat binding 1 and 2 (Trf1/Trf2), DNA repair (Xrcc5),
telomerase reverse transcriptase (mTERT) and telomere length in middle aged mice.
Three groups were studied: a control group (CTL) and two groups submitted to
swimming at intensities below the lactate threshold (LI group) and above the
lactate threshold (HI group) for 40 and 20 min respectively, for 12 weeks. After
training, the HI group showed reduction in p53 expression in the muscle, and
decreased shelterin complex expression when compared to LI group. No differences
were observed between groups for mTERT expression and telomere length. Thus,
exercise training in high-intensity domain was more effective on reducing markers
of senescence and apoptosis. The higher intensity exercise training also
diminished shelterin expression, with no differences in telomere length and mTERT
expression. Such results possibly indicate a more effective DNA protection for
the higher-intensity exercise training.
PMID- 29945272
TI - Effects of Modified Pyramid System on Muscular Strength and Hypertrophy in Older
Women.
AB - This study aimed to analyze the effects of a pyramid system performed with two
repetition zones on muscular strength and skeletal muscle mass (SMM) in older
women. Thirty-nine physically independent older women (67.8+/-5.4 years) were
randomly assigned into one of two of groups that performed an 8-week resistance
training program in an ascending pyramid fashion. Both groups performed 3 sets: a
narrow repetition zone (NPR, n=20) with 12/10/8 repetitions, and a wide
repetition zone (WPR, n=19) with 15/10/5 repetitions. The program consisted of 8
whole-body exercises, performed 3 times a week. Dual-energy X-ray absorptiometry
was used to measure SMM, and muscular strength was evaluated by one-repetition
maximum (1RM). Both groups increased (P<0.05) SMM (NPR=+ 4.7%, effect size=+
0.34; WPR=+ 8.4%, effect size=+ 0.77), and total strength (NPR=+ 11.3%, effect
size=+ 0.80; WPR=+ 13.8%, effect size=0.84), without statistical differences
between them. Results suggest that both zones of repetitions in a pyramid system
are effective strategies to improve muscular strength and muscle growth in older
women.
PMID- 29945273
TI - [Correction: The Role of Context in Spoken Sentence Recognition].
PMID- 29945274
TI - [Influence of Training of Orthopaedic Surgeons on Clinical Outcome after Total
Hip Arthroplasty in a High Volume Endoprosthetic Centre].
AB - BACKGROUND: The study aims to evaluate whether the postoperative outcome and the
probability of complications of patients with total hip arthroplasty increases
significantly when surgeons in training are in charge, assisted by a high volume
surgeon, compared to a highly experienced orthopaedic surgeon, within the context
of a high volume hospital certified to EndoCert. MATERIAL AND METHODS: 192
patients with a primary hip arthroplasty were included. To assess the outcome,
the Harris Hip Score, WOMAC, SF-36 and EuroQol-5D were surveyed pre- and 12
months postoperatively. As complications we considered the quality indicators
defined by EndoCert. RESULTS: We found significant improvements in the
postoperative score values with the qualifications of the surgeon in charge, even
when a high volume surgeon or a surgeon in training was responsible. If a surgeon
in training is assisted by a highly experienced surgeon, the risk of
complications does not increase, although the operating time was significantly
increased. CONCLUSION: Both the surgeon in training as well as the arthroplasty
patient benefit from implementing the EndoCert system, because the postoperative
outcome and the complication probability is independent of the qualifcation of
the operating orthopaedic surgeon performing total hip arthroplasty when assisted
by an experienced surgeon.
PMID- 29945275
TI - Histomorphometry and Protein Expression From the Ovary and Uterine Horns of
Wistar Strain Albino Rats Treated with Methanol Leave Extract of Parquetina
Nigrescens.
AB - BACKGROUND: The effects of methanol extract of Parquetina nigrescens were studied
on histomorphometry and protein expression (SDS-PAGE) from the ovaries and uteri
of wistar rats. METHODS: 30 sexually matured rats were used for the study with 10
each in the control and treatment 100 mgkg-1 and 400 mgkg-1 groups. The extract
was orally administered for 14 days. Histological sections of tissues collected
presented no abnormalities. RESULTS: An increase in the number of developing and
matured follicles were observed during the study in the treated groups compared
to the control in the follicular and the luteal phases. The corpora lutea in the
treated groups were fewer in number to that of the control in the follicular
phase and in the luteal phase. Sections of the uterine horns showed significant
narrowing in the lumen diameter and increases in epithelial height with increased
laydown of the lamina propria in the treated groups. The expression of protein
bands fractionated during the study, confirm the presence of proteins expressed
repeatedly from the ovary and uterine horns in the follicular and luteal phases
at the 70 kDa and 63 kDa regions. CONCLUSIONS: The study concluded that the
methanol extract of the plant increased folliculogenesis on the ovary, secretory
activity in the nuclei of the epithelium and the fibroplasia of the lamina
propria while narrowing the lumen of the uterine horns which are similar to the
effects of oestrogen or oestrogen-like substances on these reproductive organs
and may have an effect on the abundance of protein expressed in the follicular
phase.
PMID- 29945276
TI - Protective but Non-Synergistic Effects of Nigella Sativa and Vitamin E against
Cisplatin-Induced Renal Toxicity and Oxidative Stress in Wistar Rats.
AB - BACKGROUND: Cisplatin is an anti-cancer drug that causes nephrotoxicity and
oxidative stress. Extracts of Nigella sativa is nephroprotective. Vitamin E is
also a potent antioxidant. This study sought to determine a possible synergistic
effect of administering the two agents prior to cisplatin use on nephrotoxicity
and oxidative stress. METHODS: 48 male Wistar rats were randomly divided into 6
groups of 8 rats each. Group I served as the control. Group II received cisplatin
without any treatment for 6 days. Groups III, IV, V and VI received 100 mg/kg
Nigella sativa (NS), 200 mg/kg NS, 100 mg/kg Vitamin E and 200 mg/kg NS+100 mg/kg
Vitamin E respectively for 5 days prior to 6 days administration of cisplatin. On
the last day of the experiment, all the animals were sacrificed and serum samples
collected for analysis. RESULTS: Cisplatin administration caused a significant
increase in creatinine level (p<0.01), urea level (p<0.01), sodium concentration
and malondialdehyde level (p<0.001). Pre-administration with NS caused a
significant reduction in creatinine level (p<0.001), urea level (p<0.001), sodium
concentration (p<0.001) and malondialdehyde (p<0.01) level. Pre-administration
with vitamin E caused a significant reduction in creatinine level (p<0.001), urea
level (p<0.01), sodium concentration (p<0.001) and malondialdehyde level. They
both also caused a significant increase in superoxide dismutase, reduced
glutathione and catalase (CAT) levels. The combination of NS and vitamin E
however did not show significant synergistic effects. CONCLUSION: These results
suggest that even though pre-administration of the two agents protect against
renal toxicity and oxidative stress, the effects are however not collaborative.
PMID- 29945277
TI - Pre-Treatment with Curcumin Ameliorates Cisplatin-Induced Kidney Damage by
Suppressing Kidney Inflammation and Apoptosis in Rats.
AB - OBJECTIVE: In addition to oxidative stress, inflammation and apoptosis have an
important role in the pathogenesis of cisplatin-induced kidney damage. This study
aimed to investigate the molecular mechanisms of protective effects of curcumin
against cisplatin-induced kidney inflammation and apoptosis in rats. MATERIALS
AND METHODS: Eighteen rats were equally divided into three groups; normal (0.5%
CMC-Na), cisplatin (CDPP) (7 mg/kg i.p.), and cisplatin+curcumin (CMN100) groups.
Curcumin was given at a dose of 100 mg/kg orally for nine days, starts one week
before giving a single dose of cisplatin. Kidney and plasma were taken for
analysis. RESULTS: Cisplatin challenged rats demonstrated kidney injury as shown
by reduced creatinine clearance, increased of plasma BUN, plasma creatinine, and
kidney MDA, decreased of kidney GSH levels, and kidney histopathology
alterations. Also, cisplatin increased ERK1/2 phosphorylation and NF-kappaB
expression, which subsequently increased mRNA expression of TNF-alpha, IL-6, KIM
1, NGAL, and Bax/Bcl-2 ratio as well as decreased mRNA expression of IL-10 in
kidney tissues. Pre-treatment with curcumin significantly ameliorated
inflammation and apoptosis induced by cisplatin. In addition, curcumin
downregulated Ctr1 and OCT2 drug transporters as compared to cisplatin group.
Histopathological examination furthers confirmed the kidney damage protection
effect of curcumin. CONCLUSIONS: These data indicate that curcumin has
nephroprotective properties against cisplatin-induced kidney damage in rats and
this effect is associated with its anti-inflammatory and anti-apoptosis profiles,
in addition to its antioxidant. Hence, curcumin may be useful for preventing
kidney damage against cisplatin administration.
PMID- 29945278
TI - Pharmacological Control of Complications Following to Third Molar Removal:
Evidence Based on A Meta-Analysis.
AB - AIMS: The purpose of this meta-analysis was to evaluate the clinical efficacy of
non-steroidal anti-inflammatory drugs and dexamethasone on the trismus,
postsurgical pain, facial swelling, as well as the analgesic consumption after
third molar surgery. MATERIAL AND METHODS: The reports were identified in the
most important medical databases. Those studies that met the requirements were
fully assessed according to the inclusion and exclusion criteria. The quality of
each report was evaluated with the Oxford Quality Scale and using the Cochrane
Collaboration's risk of bias tool. Each meta-analysis was done using the
technique of mean difference and 95% confidence intervals employing a random
effects model with the Review Manager 5.3., from the Cochrane Library.
Significant statistical difference was accepted when the p value was less than
0.05 on the test of overall effect (Z value). RESULTS: Qualitative evaluation was
done using the data of 330 patients extracted from seven articles and the
quantitative assessment with data of 200 patients from three reports. It was not
observed difference among non-steroidal anti-inflammatory drugs and dexamethasone
in any of the clinical effectiveness indicators. CONCLUSION: The outcomes of our
meta-analysis indicate that non-steroidal anti-inflammatory drugs and
dexamethasone have good therapeutic effect for the management of inflammatory
complications following to third molar surgery.
PMID- 29945279
TI - [Prophylaxis, diagnosis and therapy of hepatitis-C-virus (HCV) infection: the
German guidelines on the management of HCV infection - AWMF-Register-No.:
021/012].
PMID- 29945280
TI - Current Practices of Antiseptic Use in Canadian Neonatal Intensive Care Units.
AB - OBJECTIVE: This article assesses the degree of variability in the current
practice of skin antiseptics used in Canadian neonatal intensive care units
(NICUs) and different experiences related to each antiseptic used. METHODS: An
anonymous survey was distributed to a clinical representative of each of the 124
Canadian level II and level III NICUs. RESULTS: One hundred and two respondents
(82.2%), representing all Canadian provinces, completed the survey. Chlorhexidine
gluconate with/without alcohol was the antiseptic most used (96%) and the
antiseptic with the highest reported adverse effects (68% reported skin
burns/breakdown). Other antiseptics used include povidone-iodine (35%) and
isopropyl alcohol (22%). Specific guidelines for antiseptic use were available in
only 50% of the units with many NICUs lacking gestational and/or chronological
age restrictions. Only 23% of responders believed that there was awareness among
health care providers of the adverse effects of antiseptics used. Less than half
(43%) were completely satisfied with the antiseptics used in their units.
CONCLUSION: Chlorhexidine gluconate is the most commonly used antiseptic in
Canadian NICUs. The high number of associated adverse effects and the lack of
guidelines regulating antiseptic use are of concern. Large clinical trials are
urgently needed to guide practice and improve the safety of antiseptics.
PMID- 29945282
TI - ?
PMID- 29945281
TI - Acetaminophen and Acetylsalicylic Acid Exposure in a Preterm Infant after
Maternal Overdose.
AB - Here, we review the case of a 26 1/7 weeks' gestation premature female infant
born to a mother who intentionally ingested a large quantity of Tylenol, aspirin,
quetiapine, and prenatal vitamins. The neonate subsequently had markedly elevated
levels of both Tylenol and aspirin when checked on the first day of life. While
overall clinically stable, the neonate did demonstrate coagulopathy as evidenced
by abnormal coagulation studies. Both poison control and a pediatric
gastroenterologist/hepatologist were consulted. She successfully tolerated a
course of N-acetylcysteine; her subsequent Tylenol level was markedly decreased
and the neonate exhibited no further effects of toxicity. The salicylate level
decreased on its own accord. To our knowledge, this is the first report of a
neonate at 26 weeks' gestation that has been successfully managed for
supratherapeutic concentrations of acetaminophen and acetylsalicylic acid
secondary to maternal ingestion. While rare, this case may serve as a reference
for the effectiveness of N-acetylcysteine in premature infants in such instances.
PMID- 29945283
TI - [Point of Care 2.0: Coagulation Monitoring Using Rotem(r) Sigma and Teg(r) 6S].
AB - New-generation methods for point of care based coagulation monitoring enable
fully automated viscoelastic analyses for the assessment of particular parts of
hemostasis. Contrary to the measuring techniques of former models, the
viscoelastic ROTEM(r) sigma and TEG(r) 6s analyses are performed in single-use
test cartridges without time- and personnel-intensive pre-analytical procedures.
This review highlights methodical strengths and limitations of the devices and
meets concerns associated with their integration in routine clinical practice.
PMID- 29945284
TI - [Point-of-care Coagulation Testing in Neurosurgery].
AB - Disorders of the coagulation system can seriously impact the clinical course and
outcome of neurosurgical patients. Due to the anatomical location of the central
nervous system within the closed skull, bleeding complications can lead to
devastating consequences such as an increase in intracranial pressure or
enlargement of intracranial hematoma. Point-of-care (POC) devices for the testing
of haemostatic parameters have been implemented in various fields of medicine.
Major advantages of these devices are that results are available quickly and that
analysis can be performed at the bedside, directly affecting patient management.
POC devices allow identification of increased bleeding tendencies and therefore
may enable an assessment of hemorrhagic risks in neurosurgical patients. Although
data regarding the use of POC testing in neurosurgical patients are limited, they
suggest that coagulation testing and hemostatic therapy using POC devices might
have beneficial effects in this patient population. This article provides an
overview of the application of point-of-care coagulation testing in clinical
practice in neurosurgical patients.
PMID- 29945285
TI - [Point-of-Care Testing in Trauma Patients - Methods and Evidence].
AB - In severely injured patients, trauma-induced coagulopathy (TIC) present at
hospital admission is associated with increased transfusion requirements,
morbidity and mortality. Early and effective treatment contributes to improved
survival rates. Laboratory coagulation assays have long turn-around times and
evidence for their usefulness, especially in the context of TIC, is weak. Due to
the lack of appropriate guidance, transfusion of allogeneic blood products
frequently follows a ratio-based concept (e.g., transfusion of erythrocytes and
plasma in a 1 : 1 ratio). Point-of-care (PoC) tests enable the assessment of
prothrombin time (PT) and activated partial thromboplastin time in few minutes.
However, although normal PT in these tests allows to rule out relevant effects of
several anticoagulants, they are not able to detect patients with TIC and/or
requiring subsequent massive transfusion. Viscoelastic tests (VETs) make it
possible to assess defects in thrombin generation, hypofibrinogenaemia,
thrombocytopenia, and hyperfibrinolysis, and thus enable targeted therapy.
Impairment of platelet function is the common blind spot not detectable using
both standard laboratory-based tests and VETs. However, PoC platelet function
tests enable to detect platelet defects and patients taking anti-platelet.
Furthermore, impaired platelet function has been identified as a strong predictor
for coagulopathy and massive transfusion in trauma patients. In other clinical
settings, coagulation management based on VETs is associated with decreased
transfusion requirements, incidence of acute kidney failure, and mortality,
respectively. Data of the first small prospective randomised trial indicate
superiority of VET guided coagulation management solely using coagulation factor
concentrates, when compared to plasma transfusions in severe trauma.
PMID- 29945286
TI - [Safe Vascular Access - the Guideline of the Association of Anaesthesists of
Great Britain and Ireland 2016].
AB - This guideline was presented in 2016 due to the need for an up to date evidence
based guidance focusing on patient safety. In addition to safety-related aspects
of catheter insertion or removal, organisational issues and structured training
concepts were discussed. The guideline was created based on the review of current
literature as well as expert opinion. The article summarizes and discusses the
most important recommendations and the reader is provided with practical advice
for catheter insertion or removal with the intention to improve the safety of the
patients.
PMID- 29945287
TI - [Role of Nutrition Support in Cardiac Surgery Patients - an Overview].
AB - Cardiac surgery patients regularly experience a systemic inflammation response to
the surgery and a postoperative stay in the intensive care unit. Nutritional
support is one strategy to improve the outcome of cardiosurgical patients. A
preoperatively diagnosed malnutrition contributes to a higher morbidity and
mortality in this patient group. Preoperative fasting, glucose-free infusions
during long and invasive operations and delayed postoperative nutrition therapy
aggravate the nutrition situation. However, conclusive evidence for this
population, consisting of well-conducted clinical trials is lacking.This article
outlines the main causes for malnutrition in cardiosurgical patients and
summarizes possibilities to identify patients at high nutritional risk, who are
most likely to profit from aggressive nutritional therapy. Despite conspicuous
knowledge and evidence gaps, a rational nutritional support therapy based on
current recommendations of ASPEN, ESPEN and an international multidisciplinary
consensus group is presented. The amount and kind of nutrition, as well as the
best time to initiate nutrition support, ways to monitor nutrition therapy and
the potential use of pharmaconutrition to modulate the inflammatory response to
cardiopulmonary bypass are presented to benefit patients undergoing cardiac
surgery.
PMID- 29945288
TI - Predictors of Clinical Outcome after Reconstruction of Complex Soft Tissue
Defects Involving the Achilles Tendon with the Composite Anterolateral Thigh Flap
with Vascularized Fascia Lata.
AB - BACKGROUND: The composite anterolateral thigh flap with vascularized fascia lata
(ALT-FL flap) for covering complex soft tissue defects involving the Achilles
tendon has shown promising results. The age and body mass index (BMI) are
important predictors of clinical outcome after surgical treatment of Achilles
tendon ruptures. In this study, we investigate whether these also influence the
outcome of patients after Achilles tendon reconstruction using the ALT-FL flap.
METHODS: Twenty patients (mean age: 55.9 +/- 8.7 years) with complex tissue
defects involving the Achilles tendon underwent reconstruction with the ALT-FL
flap. Both the Achilles tendon Total Rupture Score (ATRS) and the American
Orthopaedic Foot and Ankle Society (AOFAS) score were assessed preoperatively and
12 months postoperatively. In addition, postoperative magnetic resonance imaging
(MRI) studies and measurements of the ankle range of motion were performed and
results compared with existing literature. RESULTS: All flaps survived and MRI
studies confirmed complete anatomical integration of the fascia lata as
"neotendon" at the recipient site. In our patient cohort, the age did not
correlate with the outcome measurements, whereas the BMI showed significant
negative correlation with the postoperative ATRS (p < 0.001) and AOFAS scores (p
< 0.05). The ATRS and AOFAS scores of all patients improved significantly (p <
0.001). However, obese patients with a BMI of more than 30 kg/m2 achieved
significant lower ATRS (p < 0.001) and AOFAS scores (p < 0.01), as well as
patients with peripheral artery disease (PAD) (p < 0.05). The mean ankle range of
motion after ALT-FL flap reconstruction remained statistical insignificant
compared with previous avascular or vascularized tendon repairs of the Achilles
tendon. CONCLUSION: The ALT-FL flap enables reconstruction of complex tissue
defects involving the Achilles tendon with good functional results. However, the
presence of an increased BMI or PAD, but not necessarily the age, proves to be a
predictor of poor clinical outcome and therefore should be subject to scrutiny
during patient selection.
PMID- 29945289
TI - Cell-Based Therapies in Vascularized Composite Allotransplantation.
AB - BACKGROUND: Dendritic cells (DCs) are bone marrow-derived, professional antigen
presenting cells with tolerogenic function. The ability of DCs to regulate
alloantigen-specific T cell responses and to promote tolerance has aligned them
ideally for a role in vascularized composite allotransplantation (VCA). In this
study, we summarize the current evidence for DC therapies for tolerance induction
to alleviate the requirement for chronic immunosuppression. METHOD: A
comprehensive and structured review of manuscripts published on VCA was performed
using the MEDLINE and PubMed databases. All eligible studies published from the
year 2000 to 2017 were included in the final results. RESULT: Nineteen original
preclinical and clinical studies that employed cell therapy for VCA were included
in this review. In vivo DC therapy was found to direct the alloimmune response
toward either transplant rejection or tolerance in VCA models. While injection of
mature DCs rapidly increases T-cell activity in humans and promotes transplant
rejection, the injection of immature DCs acts as an immunosuppressant and
inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells
were also found to have a positive effect on allotransplantation of solid organs
and bone marrow via cytokine expression which decreases the alloreactive effector
lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings,
the efficacy of cell-based therapies varies greatly across studies, partly due to
different methods of cell isolation and purification techniques, source, route
and timing of administration, and combination immunosuppressive therapy.
CONCLUSION: Additional research is needed to evaluate the efficacy and safety of
DC and other cell-based therapeutic measures in human allotransplant recipients.
Future direction will focus on the development of novel methods to reduce
immunosuppression and develop more individualized management, as well as the
clinical application of basic research in the mechanisms of immunologic
tolerance.
PMID- 29945290
TI - Pigmented lesions of the oral mucosa: A cross-sectional study of 458
histopathological specimens.
AB - OBJECTIVES: To evaluate clinical, demographic, and histopathological
characteristics of pigmented lesions of the oral mucosa. MATERIALS AND METHODS: A
cross-sectional study was conducted over a 64-year period. Information was
collected from medical charts, and all archived histopathological specimens with
diagnoses of any pigmented lesion were retrieved. Statistical analysis was
performed using SPSS software. RESULTS: A total of 34,127 archived specimens were
reviewed, revealing 458 (1.34%) pigmented lesions, of which 230 were melanocytic
and 228 nonmelanocytic. Most patients were females (74.2%), white-skinned
(49.1%), in the third and seventh decades of life (mean of 45 years). Most
lesions were macular (59.8%), followed by plaques and nodules (4.8%), measuring 0
5 mm (41.9%). Cheek mucosa (21.0%), alveolar mucosa (16.6%), and gingiva (11.8%)
were the most commonly affected sites. Amalgam tattoo was applied in 212 cases
(46.3%), followed by melanotic macule (22.9%) and nevus (20.5%). Other diagnoses
included racial pigmentation, exogenous pigmentation, melanotic neuroectodermal
tumor of infancy, melanoma, melanoacanthoma, smoker's melanosis, and heavy metal
pigmentation. CONCLUSIONS: Pigmented lesions represent an uncommon diagnosis in
oral pathology routines. The most frequent entities are amalgam tattoo, melanotic
macule, and nevus. Patients are usually middle-aged women presenting a small,
long-lasting, macular lesion on the cheek mucosa.
PMID- 29945291
TI - GLUCOLD, eosinophils and chronic obstructive pulmonary disease.
PMID- 29945293
TI - Evaluation of three pain assessment scales used for ventilated neonates.
AB - AIMS AND OBJECTIVES: To compare and evaluate the reliability, validity,
feasibility, clinical utility, and nurses' preference of the Premature Infant
Pain Profile-Revised, the Neonatal Pain, Agitation, and Sedation Scale, and the
Neonatal Infant Acute Pain Assessment Scale used for procedural pain in
ventilated neonates. BACKGROUND: Procedural pain is a common phenomenon but is
undermanaged and underassessed in hospitalised neonates. Information for
clinician selecting pain measurements to improve neonatal care and outcomes is
still limited. DESIGN: A prospective observational study was used. METHODS: A
total of 1,080 pain assessments were made at 90 neonates by two nurses
independently, using three scales viewing three phases of videotaped painful
(arterial blood sampling) and nonpainful procedures (diaper change). Internal
consistency, inter-rater reliability, discriminant validity, concurrent validity
and convergent validity of scales were analysed. Feasibility, clinical utility
and nurses' preference of scales were also investigated. RESULTS: All three
scales showed excellent inter-rater coefficients (from 0.991-0.992) and good
internal consistency (0.733 for the Premature Infant Pain Profile-Revised, 0.837
for the Neonatal Pain, Agitation, and Sedation Scale and 0.836 for the Neonatal
Infant Acute Pain Assessment Scale, respectively). Scores of painful and
nonpainful procedures on the three scales changed significantly across the
phases. There was a strong correlation between the three scales with adequate
limits of agreement. The mean scores of the Neonatal Pain, Agitation, and
Sedation Scale for feasibility and utility were significantly higher than those
of the Neonatal Infant Acute Pain Assessment Scale, but not significantly higher
than those of the Premature Infant Pain Profile-Revised. The Neonatal Pain,
Agitation, and Sedation Scale was mostly preferred by 55.9% of the nurses,
followed by the Neonatal Infant Acute Pain Assessment Scale (23.5%) and the
Premature Infant Pain Profile-Revised (20.6%). CONCLUSIONS: The three scales are
all reliable and valid, but the Neonatal Pain, Agitation, and Sedation Scale and
the Neonatal Infant Acute Pain Assessment Scale perform better in reliability.
The Neonatal Pain, Agitation, and Sedation Scale appears to be a better choice
for frontier nurses to assess procedural pain in ventilated neonates based on its
good feasibility, utility and nurses' preference. RELEVANCE TO CLINICAL PRACTICE:
Choosing a valid, reliable, feasible and practical measurement is the key step
for better management of procedural pain for ventilated newborns. Using the right
and suitable tool is helpful to accurately identify pain, ultimately improve the
neonatal care and outcomes.
PMID- 29945292
TI - Activating the pregnane X receptor by imperatorin attenuates dextran sulphate
sodium-induced colitis in mice.
AB - BACKGROUND AND PURPOSE: Activation of the human pregnane X receptor (PXR; NR1I2)
has potential therapeutic uses for inflammatory bowel disease (IBD). Imperatorin
(IMP), a naturally occurring coumarin, is the main bioactive ingredient of
Angelica dahurica Radix, which is regularly used to treat the common cold and
intestinal disorders. However, there are no data on the protective effects of IMP
against IBD. EXPERIMENTAL APPROACH: The effects of IMP on PXR-modulated
cytochrome P450 3A4 (CYP3A4) expression were assessed using a PXR transactivation
assay, a mammalian two-hybrid assay, a competitive ligand-binding assay, analysis
of CYP3A4 mRNA and protein expression levels and measurement of CYP3A4 activity
using a cell-based reporter gene assay and in vitro model. The inhibitory effects
of IMP on NF-kappaB activity were evaluated by a reporter assay and NF-kappaB p65
nuclear translocation. The anti-IBD effects of IMP were investigated in a dextran
sulphate sodium (DSS)-induced colitis mouse model. Colon inflammatory cytokines
were assessed by elisa. KEY RESULTS: IMP activated CYP3A4 promoter activity,
recruited steroid receptor coactivator 1 to the ligand-binding domain of PXR and
increased the expression and activity of CYP3A4. PXR knockdown substantially
reduced IMP-induced increase in CYP3A4 expression. Furthermore, IMP-mediated PXR
activation suppressed the nuclear translocation of NF-kappaB and down-regulated
LPS-induced expression of pro-inflammatory genes. Nevertheless, PXR knockdown
partially reduced the IMP-mediated inhibition of NF-kappaB. IMP ameliorated DSS
induced colitis by PXR/NF-kappaB signalling. CONCLUSIONS AND IMPLICATIONS: IMP
acts as a PXR agonist to attenuate DSS-induced colitis by suppression of the NF
kappaB-mediated pro-inflammatory response in a PXR/NF-kappaB-dependent manner.
PMID- 29945295
TI - Therapeutic equivalence of two formulations of calcipotriol-betamethasone
ointment: a multicentre, randomized, double-blind study in adult patients with
chronic plaque psoriasis.
PMID- 29945294
TI - Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9
in detecting pancreatic cancer.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few
biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.9), the
most frequently used biomarker for PDAC, is not sensitive and specific enough for
the detection of the disease. This study aimed to evaluate serum periostin
(POSTN) and CA242 as potential diagnostic biomarkers complementing CA19.9 in
detecting pancreatic cancer. Blood samples were from 362 participants, including
213 patients with different stages of PDAC, 75 patients with benign pancreatic
disease, and 74 healthy individuals. All samples were randomly divided into a
training set and a validation set. Carbohydrate antigen 19.9, CA242, POSTN, as
well as carcinoembryonic antigen, were measured by ELISA or automated
immunoassay. The receiver operating characteristic curve analysis revealed that
the performance of CA19.9 in the validation group were improved by the marker
panel composed of CA19.9, POSTN, and CA242, to discriminate early stage PDAC not
only from healthy controls (area under the curve [AUC]CA19.9 = 0.94 vs AUCCA19.9
+ POSTN + CA242 = 0.98, P < .05) but also from benign conditions (AUCCA19.9 =
0.87 vs AUCCA19.9 + POSTN + CA242 = 0.90, P < .05). In addition, POSTN retained
significant diagnostic capabilities to distinguish PDAC CA19.9-negative from
healthy controls (AUCPOSTN = 0.87) as well as from benign conditions (AUCPOSTN =
0.84) in the whole set. This study suggested that POSTN and CA242 are potential
diagnostic serum biomarkers complementing CA19.9 in detecting early pancreatic
cancer.
PMID- 29945298
TI - Reinvestigation of Phryganella paradoxa (Arcellinida, Amoebozoa) Penard 1902.
AB - A major drawback in testate amoeba research is a general lack of scientific
studies combining molecular approaches and classical laboratory experiments. We
isolated five yet uncultured testate amoebae of the genus Phryganella Penard,
1902 from three different rivers and one pond in Germany. Based on established
cultures we show their morphology, which we studied by light and electron
microscopy, and present their unique feeding mode on abundant and common pennate
diatoms like Nitzschia spp. and Synedra spp., whose frustules are bent and
frequently, but not always, broken during the feeding process. We further
obtained the first SSU rDNA sequences of strains of the family Phryganellidae,
all of which contain introns. We used the sequences to confirm the taxonomic
placement of the Phryganellidae in the Arcellinida (Amoebozoa), branching as a
sister group to the Cryptodifflugiidae.
PMID- 29945296
TI - EWS-FLI1 regulates a transcriptional program in cooperation with Foxq1 in mouse
Ewing sarcoma.
AB - EWS-FLI1 constitutes an oncogenic transcription factor that plays key roles in
Ewing sarcoma development and maintenance. We have recently succeeded in
generating an ex vivo mouse model for Ewing sarcoma by introducing EWS-FLI1 into
embryonic osteochondrogenic progenitors. The model well recapitulates the
biological characteristics, small round cell morphology, and gene expression
profiles of human Ewing sarcoma. Here, we clarified the global DNA binding
properties of EWS-FLI1 in mouse Ewing sarcoma. GGAA microsatellites were found to
serve as binding sites of EWS-FLI1 albeit with less frequency than that in human
Ewing sarcoma; moreover, genomic distribution was not conserved between human and
mouse. Nevertheless, EWS-FLI1 binding sites within GGAA microsatellites were
frequently associated with the histone H3K27Ac enhancer mark, suggesting that EWS
FLI1 could affect global gene expression by binding its target sites. In
particular, the Fox transcription factor binding motif was frequently observed
within EWS-FLI1 peaks and Foxq1 was identified as the cooperative partner that
interacts with the EWS portion of EWS-FLI1. Trib1 and Nrg1 were demonstrated as
target genes that are co-regulated by EWS-FLI1 and Foxq1, and are important for
cell proliferation and survival of Ewing sarcoma. Collectively, our findings
present novel aspects of EWS-FLI1 function as well as the importance of GGAA
microsatellites.
PMID- 29945300
TI - Who put the 'paediatric' in paediatric eye care?
PMID- 29945299
TI - Perforated viscus; not always bowel: case report of spontaneous bladder rupture.
PMID- 29945297
TI - Profilin 1 induces drug resistance through Beclin1 complex-mediated autophagy in
multiple myeloma.
AB - Autophagy plays an important role in multiple myeloma (MM) for homeostasis,
survival and drug resistance, but which genes participate in this process is
unclear. We identified several cytoskeleton genes upregulated in MM patients by
gene expression profiling (GEP) datasets; in particular, patients with high
profilin 1 (PFN1) expression had poor prognosis in MM. In vitro, overexpressed
PFN1 promotes proliferation and bortezomib (BTZ) resistance in MM cells. Further
study indicated overexpression of PFN1 significantly promoted the process of
autophagy and induced BTZ resistance in MM. Otherwise, knockdown of PFN1 blocked
autophagy and sensitized MM to BTZ. Co-immunoprecipitation in MM cells indicated
that PFN1 could bind Beclin1 complex and promote the initiation of autophagy.
Inhibition of autophagy by blocking the formation of Beclin1 complex could
reverse the phenotype of BTZ resistance in MM. Our findings suggested that PFN1
could promote autophagy through taking part in Beclin1 complex and contribute to
BTZ resistance, which may become a novel molecular target in the therapy of MM.
PMID- 29945301
TI - Relationship and probabilistic stratification of Eczema Area and Severity Index
and objective Scoring Atopic Dermatitis severity scores for atopic dermatitis.
PMID- 29945302
TI - Fragrance exposure in the U.K.: has there been a change in the last decade?
PMID- 29945303
TI - Characteristics of interruptions during medication administration: An integrative
review of direct observational studies.
AB - AIMS AND OBJECTIVES: To synthesise and summarise data gathered by direct
observation of the characteristics of interruptions in the context of nursing
medication administration (MA) in hospital settings. BACKGROUND: Interruptions
are prevalent during the MA process performed by nurses in hospital settings and
have been found to be associated with an increase in frequency and severity of
nursing MA errors. In addition, interruptions decrease task efficiency, leading
to longer MA completion times. DESIGN: Integrative review. METHODS: The
electronic databases Cumulative Index to Nursing and Allied Health Literature
(CINAHL), PubMed, PsycARTICLES and Google Scholar were searched using the terms
"interruptions" AND "medication administration" AND "direct observation." Nine
articles met the inclusion criteria. RESULTS: Interruptions are likely to occur
at least once during nursing MA processes in hospital settings. This finding
applies to medication administered to one patient, termed a medication pass, and
medication administered to multiple patients, termed a medication round.
Interruptions are most commonly caused by another nurse or staff member or are
self-initiated, and last approximately 1 min in length. CONCLUSIONS: A raised
awareness among staff of the most common sources of interruptions may encourage
changes that lead to a decrease in the occurrence of interruptions. In addition,
nurse leaders can apply an understanding of the common characteristics of
interruptions to guide research, policies and educational methods aimed at
interruption management strategies. RELEVANCE TO CLINICAL PRACTICE: The findings
from this review can be used to guide the identification and development of
targeted interventions and strategies that would have the most substantial impact
to reduce and manage interruptions during MA. Interruption management strategies
have the potential to lead to a decrease in medication errors and an increase in
task efficiency.
PMID- 29945304
TI - Flexible alpha allocation strategies for confirmatory adaptive enrichment
clinical trials with a prespecified subgroup.
AB - Adaptive enrichment designs have recently received considerable attention as they
have the potential to make drug development process for personalized medicine
more efficient. Several statistical approaches have been proposed so far in the
literature and the operating characteristics of these approaches are extensively
investigated using simulation studies. In this paper, we improve on existing
adaptive enrichment designs by assigning unequal weights to the significance
levels associated with the hypotheses of the overall population and a
prespecified subgroup. More specifically, we focus on the standard combination
test, a modified combination test, the marginal combination test, and the partial
conditional error rate approach and explore the operating characteristics of
these approaches by a simulation study. We show that these approaches can lead to
power gains, compared to existing approaches, if the weights are chosen
carefully.
PMID- 29945305
TI - Patients prioritize waitlist over posttransplant outcomes when evaluating kidney
transplant centers.
AB - Factors that patients value when choosing a transplant center have not been well
studied. In order to guide the improvement of patient-facing materials, we
conducted an anonymous electronic survey of patients that assessed the relative
importance of patient experience, practical considerations, transplant center
reputation, center experience, and waitlist when selecting a transplant center. A
total of 409 respondents completed the survey, of whom 68% were kidney transplant
recipients and 32% had chronic kidney disease or were on dialysis. Participants
had mean age 56 +/- 12 years and were predominantly female (61%), white (79%),
and had an associate's degree or higher (68%). Participants most often
prioritized waitlist when evaluating transplant centers (transplanted 26%,
chronic kidney disease 40%), and waitlist was almost twice as likely as outcomes
to be ranked most important (30% vs 17%). Education level and transplant status
were significantly associated with factors used for center prioritization.
Waitlisted respondents most commonly (48%) relied on physicians for information
when selecting a center, while a minority cited transplant-specific
organizations. In order to improve shared decision-making, materials outlining
center-specific waitlist features should be prioritized. Novel patient-oriented
metrics for measuring transplant center quality that align with patient
priorities must be explored.
PMID- 29945306
TI - In Vitro Study of Bacteriophage AB3 Endolysin LysAB3 Activity Against
Acinetobacter baumannii Biofilm and Biofilm-Bound A. baumannii.
AB - BACKGROUND: The increase in the prevalence of drug-resistant Acinetobacter
baumannii is a serious public health concern, which is closely linked to the
formation of biofilm. It is reported that the bacteriophage and its endolysin
have a good ability to degrade biofilms. The goals of this study were to compare
the ability of A. baumannii bacteriophage AB3, its endolysin AB3, and three
antibiotics to degrade A. baumannii biofilm and biofilm-bound A. baumannii and to
understand the antibacterial mechanism of LysAB3. METHODS: The 558-bp sequence of
the LysAB3 gene was amplified by polymerase chain reaction (PCR); the fragment
was cloned into pET28a (+) to construct the recombinant plasmid pET28a-LysAB3,
which was then expressed in E. coli BL21 (DE3) to obtain the LysAB3. Differences
in A. baumannii biofilm and biofilm-bound A. baumannii after treatment with
bacteriophage AB3, LysAB3 or three antibiotics were examined using the crystal
violet staining method and an MTT (3-[4,5-dimethylthiazole-2-yl]-2,5
diphenyltetrazolium bromide) assay. Changes in biofilm morphology and thickness
in each treatment group were observed by laser scanning confocal microscopy. In
addition, a LysAB3 construct with the amphiphilic peptide structural region
removed (LysAB3-D) was assessed for its antibacterial activity. RESULTS: After 24
hour treatment with either bacteriophage AB3 and its LysAB3, A. baumannii
biofilms were significantly degraded, and the number of viable biofilm-bound A.
baumannii were also significantly decreased. After removing the amphiphilic
peptide structure motif from LysAB3, the antibacterial activity decreased from
95.8% to 33.3%. CONCLUSIONS: Thus, LysAB3 can effectively degrade A. baumannii
biofilm and biofilm-bound A. baumannii in vitro. The antibacterial mechanism of
LysAB3 may be associated with the ability of the amphiphilic peptide structural
region to enhance the permeability of cytoplasmic membrane of A. baumannii by
degradation of bacterial wall peptidoglycan.
PMID- 29945307
TI - Demonstration of IgG Subclass (IgG1 and IgG3) in Immuno-Related Hemocytopenia.
AB - BACKGROUND: Immuno-related hemocytopenia (IRH) is defined as idiopathic cytopenia
of undetermined significance (ICUS) patients with autoantibodies. In our previous
studies, we found that IgG1 levels were increased in IRH patients and might cause
the destruction of hematopoietic cells. METHODS: In this study, we analyzed IgG
subclasses in 30 IRH patients (male:female = 13:17, median age 32 years, range 18
- 56), 15 IRH remission patients (IRH-R) (male:female = 6:9, median age 34, range
20 - 52) and 20 normal controls (male:female = 8:12, median age 27, range 24 -
36) by Cytometric Bead Array, Flow Cytometry and Immunohistochemical staining.
RESULTS: Levels of IgG1/IgG3 in the bone marrow supernatant of IRH patents, as
well as the proportion of CD5+ B lymphocytes and Th2 cells (CD3+CD8-IL-4+) were
higher than those of IRH-R patients and normal controls, and IgG1 levels had a
positive correlation with the proportion of Th2 cells. In IRH patients, IgG1 and
IgG3 were positive on nucleated erythrocytes and granulocytes, which were
negative in IRH-R patients and healthy controls and had inverse correlations with
hematopoietic function. Using immunohistochemical staining, IgG1 were also
detected on bone marrow biopsies of IRH patients. CONCLUSIONS: The results
indicated that IgG1 and IgG3 autoantibodies in IRH patients might play a key role
in the IRH pathogenesis and in the abnormal immune function of IRH patients.
PMID- 29945308
TI - Aberrant Expression of miR-142-3p and its Target Gene HMGA1 and FZD7 in Breast
Cancer and its Clinical Significance.
AB - BACKGROUND: Breast cancer is the second leading cause of cancer-related death
among women worldwide. The aim of this study is to investigate the role of miR
142-3p in breast cancer cells and the related mechanism. METHODS: Sixty paired
breast cancer tissues were collected and 60 breast tissues from patients with
mammary hyperplasia served as the control group. The expression of miR-142-3p was
examined using RT-qPCR methods; moreover, we also performed receiver operating
characteristic (ROC) curve analysis to determine whether miR142-3p can
distinguish breast cancer patients from the controls. Next, HMGA1 and FZD7 have
been predicted as target genes of miR-142-3p, and the expressions of HMGA1 and
FZD7 in breast cancer tissue and the control group were examined using RT-qPCR
and western blot methods. RESULTS: miR-142-3p was significantly down-regulated in
breast cancer tissue compared with the controls, and the levels of miR-142-3p was
negatively correlated with the tumor size, degree of differentiation, and
metastasis (p < 0.01). Moreover, results of ROC curve analysis indicated that the
expression of miR-142-3p can distinguish between patients with breast cancer and
the control group (AUC = 0.819, 95% CI, 0.756 - 0.881). Furthermore, the
expressions of HMGA1 and FZD7 were significantly up-regulated in patients with
breast cancer compared with the controls. The level of miR-142-3p was negatively
correlated with expressions of HMGA1 (r = -0.3507, p = 0.006) and FZD7 (r =
0.3410, p = 0.0077) in patients with breast cancer. CONCLUSIONS: Our results
proved that miR-142-3p may serve as a tumor suppressor in breast cancer by
suppressing the expression of oncogene HMGA1 and FZD7, suggesting that miR-142-3p
has the potential to become a diagnostic marker and therapeutic target for the
early diagnosis and treatment of breast cancer.
PMID- 29945309
TI - Design and Development of a Quantitative TaqMan Real-Time PCR Assay for
Evaluation of HIV-1 (group M) Viral Load in Plasma Using Armored RNA Standard.
AB - BACKGROUND: Human immunodeficiency virus-1 (HIV-1) is a viral infectious agent
that gradually extinguishes the immune system, resulting in the acquired immune
deficiency syndrome (AIDS). The aim of this study was to develop a TaqMan based
detection assay to evaluate HIV-1 plasma viral load and to construct a stable
internal positive control (IPC) and external positive control (EPC) RNA based on
Armored RNA (AR) technology. METHODS: The MS2 maturase, coat protein gene and HIV
1 pol gene were cloned in pET-32a plasmid. The recently fabricated recombinant
plasmid was transformed into Escherichia coli strain BL2 (DE3) and protein
expression and Armored RNA was fabricated in presence of isopropyl-L-thio-D
galactopyranoside (IPTG). The Armored RNA was precipitated and purified by
polyethylene glycol (PEG) and sephacryl S-200 chromatography. The stability of
Armored RNA was evaluated by treatment with DNase I and RNase A and confirmed by
transmission electron microscopy (TEM) and gel agarose electrophoresis. The
specificity, sensitivity, inter- and intra-day precision, and the dynamic range
of the assay were experimentally determined. RESULTS: The AR was stable in
presence of ribonuclease, and the assay had a dynamic detection range from 101 to
105 copies of AR. The coefficient of variation (CV) was 4.8% for intra-assay and
5.8% for inter-assay precision. Clinical specificity and sensitivity of the assay
were assessed at 100% and 96.66%, respectively. The linear regression analysis
confirmed a high correlation between the in-house and the commercial assay, Real
Star HIV-1-qRTPCR, respectively (R2 = 0.888). CONCLUSIONS: The AR standard is non
infectious and highly resistant in the presence of ribonuclease. The TaqMan assay
developed is able to quantify HIV viral load based on a novel conserved region of
HIV-1 pol gene which has minimal sequence inconsistency.
PMID- 29945310
TI - Study of Staphylococcus aureus N315 Pathogenic Genes by Text Mining and
Enrichment Analysis of Pathways and Operons.
AB - BACKGROUND: Staphylococcus aureus (S. aureus) is a versatile pathogen found in
many environments and can cause nosocomial infections in the community and
hospitals. S. aureus infection is an increasingly serious threat to global public
health that requires action across many government bodies, medical and health
sectors, and scientific research institutions. METHODS: In the present study, S.
aureus N315 genes that have been shown in the literature to be pathogenic were
extracted using a bibliometric method for functional enrichment analysis of
pathways and operons to statistically discover novel pathogenic genes associated
with S. aureus N315. RESULTS: A total of 383 pathogenic genes were mined from the
literature using bibliometrics, and subsequently a few new pathogenic genes of S.
aureus N315 were identified by functional enrichment analysis of pathways and
operons. CONCLUSIONS: The discovery of these novel S. aureus N315 pathogenic
genes is of great significance to treat S. aureus induced diseases and identify
potential diagnostic markers, thus providing theoretical fundamentals for
epidemiological prevention.
PMID- 29945311
TI - Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker
for Colorectal Cancer.
AB - BACKGROUND: Periostin (POSTN) plays an important role in numerous cancers,
especially in gastrointestinal malignancy. The objective of this study was to
investigate the diagnostic and prognostic role of serum POSTN in colorectal
cancer (CRC). METHODS: Serum periostin, together with CEA, CA19.9, CA72.4, and
CA242 levels were measured in samples from 108 patients with CRC and 56 healthy
controls, and their correlation with clinical characteristics was further
analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank
analyses were used to evaluate diagnostic and prognostic significance. RESULTS:
Serum POSTN levels were significantly higher in patients with CRC compared with
healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001).
ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and
CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN
retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative
CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower
serum POSTN had longer overall survival than those with high serum POSTN (p =
0.0146). CONCLUSIONS: Serum POSTN might be a novel diagnostic and prognostic
biomarker for patients with CRC.
PMID- 29945312
TI - Interchangeability of Procalcitonin Measurements Using the Point of Care Testing
i-CHROMATM Reader and the Automated Liaison XL.
AB - BACKGROUND: Our aim was to verify if procalcitonin (PCT) measurements using the
new point-of-care testing i-CHROMATM are interchangeable with those of Liaison
XL. METHODS: One hundred seventeen serum samples were processed sequentially on a
Liaison XL and i-CHROMATM. Statistical analysis was done using the Passing-Bablok
regression, Bland-Altman test, and Cohen's Kappa statistic. RESULTS: Proportional
and constant differences were observed between i-CHROMATM and Liaison XL. The 95%
CI of the mean bias% was very large, exceeding the maximum allowable TE% and the
clinical reference change value. However, the concordance between methods at the
clinical relevant cutoffs was strong, with the exception of the 0.25 ng/mL cutoff
which was moderate. CONCLUSIONS: Our data suggest that i-CHROMATM is not
interchangeable with Liaison XL. However, while the strong concordance at the
clinical relevant cutoffs allows us to consider i-CHROMATM a suitable option to
Liaison XL to support clinicians' decision-making; nevertheless, the moderate
agreement at the 0.25 ng/mL cutoff recommends caution in interpreting the data
around this cutoff.
PMID- 29945313
TI - Age and Gender-Specific Reference Intervals for ProGRP in Healthy Chinese Han
Ethnic Adults using the Roche Cobas Immunoassay.
AB - BACKGROUND: Pro-gastrin-releasing peptide (ProGRP) is a kind of tumor marker
applied more and more commonly in recent years. This study was aimed at
determining the age and gender-specific reference intervals (RIs) for ProGRP in
healthy Han ethnic adults from Guangxi, China. METHODS: A total of 2,045
apparently healthy males and 1,740 apparently healthy females aged from 21 to 90
years were included in this study. The serum ProGRP values were determined by
electrochemiluminescence immunoassay (ECLIA). The one-sided upper 95th percentile
of ProGRP concentrations were used to define the RIs. RESULTS: The reference
limits in different age groups (21 - 40, 41 - 50, 51 - 60, 61 - 70, and > 70
years) were 37.3, 39.7, 45.7, 47.3, and 61.3 pg/mL for males, and 36.3, 38.1,
42.7, 53.5, and 60.1 pg/mL for females, respectively. There was no significant
difference in the levels of ProGRP between males and females. The serum ProGRP
levels were positively correlated with age. CONCLUSIONS: We established the age
and gender-specific RIs for ProGRP in the adults from Guangxi, China. It will be
valuable for future clinical and laboratory studies.
PMID- 29945314
TI - Comparison of Plasma Exosomes by Differential Ultracentrifugation and Solvent
Precipitation Methods.
AB - BACKGROUND: Emerging evidence has identified that exosomes play a pivotal role in
intercellular signal transmission. However, the standardized purification
techniques to isolate high quality exosomes are still deficient at present. This
study was to evaluate reproducibility and efficiency of differential
ultracentrifugation and solvent precipitation-based kits by isolating plasma
derived exosomes from oral lichen planus patients. METHODS: Morphology, exosomal
biomarkers, particle size distribution, proteomic components, and protein yield
of isolated exosomes were evaluated by transmission electron microscope, western
blot, laser diffraction instrument, Coomassie staining, and BCA protein assay
kit, respectively. RESULTS: TEM displayed representative cup-shaped morphology of
exosomes and western blot identified exosomal biomarkers CD9 and CD63. The size
distribution showed that particles by differential ultracentrifugation were
mainly from 26.15 nm to 166.5 nm, while some of the particles obtained by solvent
precipitation kits were larger than 1,000 nm. In addition, exosomes isolated by
solvent precipitation kits showed a significantly higher amount of protein yield
due to plasma albumin contamination. CONCLUSIONS: Both differential
ultracentrifugation and precipitation based kits could successfully isolate
plasma exosomes, and exosomes by differential ultracentrifugation were purer and
more appropriate for further proteomic analysis.
PMID- 29945315
TI - Relation of Monocyte/High-Density Lipoprotein Cholesterol Ratio with Coronary
Artery Disease in Type 2 Diabetes Mellitus.
AB - BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of
mortality of patients with type 2 diabetes mellitus, and both coronary artery
disease (CAD) and diabetes mellitus are associated with inflammation. Emerging
evidence suggests a relationship of the monocyte to high-density lipoprotein
cholesterol ratio (MHR) with the incidence and severity of CAD. The aim of the
present study was to examine the association of MHR with CAD in patients with
type 2 diabetes mellitus. METHODS: A total of 458 consecutive individuals were
enrolled, comprising 178 type 2 diabetic patients, 124 type 2 diabetes with CAD,
and 156 healthy volunteers as the controls. A multivariable logistic regression
model was used to evaluate the relationship between the MHR and CAD in type 2
diabetes, and the receiver operating characteristic (ROC) curve of MHR was used
for predicting the presence of CAD in type 2 diabetic patients. RESULTS: Values
of MHR were significantly higher in type 2 diabetic patients with CAD compared
with those without CAD and the control group. Moreover, multivariate logistic
regression analysis showed that MHR was an independent predictor of the presence
of CAD in type 2 diabetic patients (OR = 1.361, 95% CI 1.245 - 1.487, p <
0.0001). Based on the receiver operating characteristic (ROC) curve, the cutoff
value of MHR (> 8.2) in predicting the presence of CAD in type 2 diabetic
patients yields a sensitivity and specificity of 83.74% and 62.15%, respectively,
with an area under the curve of 0.795 (95% CI: 0.745 - 0.840). CONCLUSIONS: The
MHR is strongly associated with CAD in type 2 diabetes and might be a potential
biomarker to predict the presence of CAD in type 2 diabetic patients.
PMID- 29945316
TI - Evaluation of Hematological Parameters in the Differentiation of Subarachnoid
Hemorrhage and Other Headache Syndromes.
AB - BACKGROUND: In this research, the aim was to compare hematological data for the
differentiation of subarachnoid hemorrhage, migraine attack, and other headache
syndromes during consultation in emergency service. METHODS: In this research,
which was designed as retrospective case control study, hematological parameters
(WBC, HgB, HCT, PLT, lymphocyte and neutrophile counts and neutrophile/lymphocyte
rates) of the patients consulting to emergency service with SAH and migraine and
other consulting patients complaining mainly from headache and having normal
cranial CT were analysed. RESULTS: Sixty migraine attack patients (F/M:47/13), 57
SAH patients (F/M:30/27), and 53 patients except migraine having normal brain CT
(F/M:36/17) who were consulted to emergency service with headache complaint were
included in our research. WBC, Hct, HgB, MCV, PLT, MPV, LY, Neu counts, and NY/LY
rates were found to differentiate between SAH and migraine. WBC, PLT, MPV, LY,
and Neu rates were found to differentiate between SAH and HS patients. Only Hct,
HgB, MCV, and NY/LY rates were found to differ meaningfully between SAH and
migraine patients but these rates were not found to have meaningful difference
between SAH and HS patients. In addition, an increase in WBC counts and NY/LY
rates and decrease in MPV counts in ROC analysis were found to be more specific
for SAH. CONCLUSIONS: WBC, HgB, HCT, PLT, lymphocyte and Neu counts, and NY/LY
rates can indicate distinguishing SAH and migraine. WBC, HgB, HCT, PLT,
lymphocyte and Neu counts can indicate to the clinician a differentiation of SAH
and other headache syndromes.
PMID- 29945318
TI - Interpretation Difficulties of Serum Immunofixation Test in Immunoglobulin D
Multiple Myeloma with Hidden Lambda Light Chains.
AB - BACKGROUND: We report a case of immunoglobulin (Ig) D myeloma with hidden lambda
light chains in a patient whose immunofixation test was very difficult to
interpret: the IgD reacts with the anti-delta heavy chain antiserum but does not
react with anti-lambda antiserum. The band in the D heavy chain lane is unmatched
in light chain lanes and the band in lambda light chain lane migrates higher.
METHODS: To distinguish between heavy chain disease and immunoglobulin with
"hidden" light chains, the sample was exposed to a very high concentration of
anti-lambda and anti-kappa antisera for 48 hours. RESULTS: The serum
immunofixation test of the sample treated with anti-lambda showed a decrease in
the intensity of the band corresponding to D heavy chain lane as well as the
modification of its mobility confirming the presence of IgD with the hidden
lambda light chains. CONCLUSIONS: The IgD myeloma with hidden light chains
remains a rare entity, hence the interest of sensitizing health professionals to
be vigilant and ensure a good diagnosis. The proposed technique is useful,
simple, reliable, and less laborious than those previous reported in the
literature. Medical laboratories using Sebia-Hydrasys(r) system should be aware
of the described phenomenon in order to avoid identifying an IgD myeloma as a
delta heavy chain disease.
PMID- 29945317
TI - Long Non-Coding RNA in Glioma: Target miRNA and Signaling Pathways.
AB - BACKGROUND: Glioma is one of the most common and aggressive malignant tumors of
the central nervous system. METHODS: Here, we review and explore the use of long
noncoding RNA (lncRNA) as a therapeutic strategy for the targeting of gliomas.
RESULTS: LncRNA is a functional RNA molecule with no protein coding function and
is involved in the occurrence and progression of glioma. It is reported that the
activation of several signaling pathways, including the MAPK, p53, Wnt/beta
catenin, PI3K/AKT/mTOR, and epithelial mesenchymal transformation (EMT) pathways,
are involved in the regulation of gliomas. In addition, microRNAs in glioma may
also interact with lncRNAs and affect tumor growth and progression. CONCLUSIONS:
Therefore, the exploration of lncRNA participation in signaling pathway
regulatory mechanisms and the determination of the interaction between lncRNA and
miRNA may help to develop new effective therapies for the treatment of glioma.
PMID- 29945319
TI - Fragmentation of Red Blood Cells Caused Pseudothrombocytosis in a Patient.
AB - BACKGROUND: Pseudothrombocytopenia, caused by platelet (PLT) clumping, is often
found in clinical studies [1]. However, pseudothrombocytosis resulting from the
fragmentation of red blood cells (RBCs) is a very rare phenomenon. METHODS: EDTA
K2 anticoagulation was used on a sample of venous blood extracted from the
patient. A Symex XN9000 automatic blood analyzer was used to conduct CBC + DIFF
mode and CBC + DIFF + RET mode tests, stained smear microscopy. RESULTS: The
Symex XN9000 automatic blood analyzer was used to conduct CBC + DIFF mode test;
PLTs were measured at 570 x 109/L. Stained smear microscopy revealed the number
of PLTs did not conform to the instrument measured 570 x 109/L. "RET" alarm
instrument, switch to CBC + DIFF + RET mode for testing. The second test result
showed PLTs at 128 x 109/L, which accords with artificial microscopy.
CONCLUSIONS: This was a case of a very rare phenomenon: the fragmentation of RBCs
caused pseudothrombocytosis.
PMID- 29945322
TI - Clinical Efficacy of Low Molecular Heparin on Unexplained Recurrent Spontaneous
Abortion.
AB - BACKGROUND: To study the clinical effect of low molecular heparin on unexplained
recurrent spontaneous abortion (URSA). METHODS: A total of 120 URSA patients were
collected in our hospital from October 2015 to September 2017. They were divided
into two groups: control group (n = 60) and observation group (n = 60). The
patients in the control group were administered with progesterone and human
chorionic gonadotropin, and the observation group with low molecular heparin.
Pregnancy outcomes, incidence of complications in pregnancy and adverse drug
reactions were compared in the two groups. RESULTS: The pregnancy success rate of
patients in the observation group (90.00%) is higher than that in the control
group (68.33%) (p < 0.05). The incidence of complications in pregnancy in the
observation group (90.00%) is lower than those in the control group (68.33%) (p <
0.05). The incidence of adverse drug reactions between the patients in the
observation group (20.00%) and those in the control group (23.33%) showed no
significant difference (p > 0.05). CONCLUSIONS: Low molecular heparin treatment
can improve pregnancy success rate and reduce the incidence of complications in
the URSA patients. Low molecular heparin is characterized by safety and
reliability and has potential for application in clinic.
PMID- 29945320
TI - A Rare Non-Hemolytic Case of Idiopathic Cold Agglutinin Disease.
AB - BACKGROUND: Cold agglutinin disease is a very rare condition associated with
agglutination of erythrocytes in cold environment usually due to IgM type
antibodies. Other than hemolytic anemias, it may interfere with routine hemogram
tests due to miscalculation of red blood cell count (RBC) and other hemogram
parameters calculated with involvement of RBC. Awareness of the condition is
important to overcome laboratory errors. METHODS: We studied a peripheral blood
smear and repeated the hemogram test at 37 degrees C to establish the diagnosis
of cold agglutinin disease. RESULTS: Initial hemogram test results of the fifty
eight year-old man was as follows: RBC: 1.34 M/uL, hemoglobin (Hb): 12.4 g/dL,
hematocrit (Htc): 11.8%, mean corpuscular hemoglobin (MCH): 92.4 pg, and mean
corpuscular hemoglobin concentration (MCHC): 105 gr/dL. Despite the standard
indirect Coombs test being negative, repeated tests at room temperature was 4+.
We suspected cold agglutinin disease and repeated the hemogram test using the
Bain-Marie method at 37 degrees C and the test results showed RBC: 3.4 M/uL,
hemoglobin: 12.6 g/dL, hematocrit: 30.2%, MCH: 31.7 pg, and MCHC: 41.8 g/dL.
CONCLUSIONS: Inappropriate hemogram results may be a sign of underlying cold
agglutinin disease. Hemolytic anemia not always accompanies the disease; however,
cold exposure may trigger erythrocyte agglutination in vitro and may cause
erratic laboratory results.
PMID- 29945321
TI - Detection of Bacterial Meningitis Pathogens by PCR-Mass Spectrometry in
Cerebrospinal Fluid.
AB - BACKGROUND: Acute bacterial meningitis remains a life-threatening infectious
disease with considerable morbidity and mortality. DNA-based detection methods
are an urgent requisite for meningitis-causing bacterial pathogens for the
prevention of outbreaks and control of infections. METHODS: We proposed a novel
PCR-mass spectrometry (PCR-Mass) assay for the simultaneous detection of four
meningitis-causing agents, Neisseria meningitidis, Streptococcus pneumoniae,
Haemophilus influenzae, and Mycobacterium tuberculosis in the present study. A
total of 138 cerebrospinal fluid (CSF) samples (including 56 CSF culture
positive, 44 CSF culture negative, and 38 CSF control) were enrolled and analyzed
by PCR/Mass. Results were compared to real-time PCR detection. RESULTS: These
four targeting pathogens could be discriminated without cross-reaction by the
accurate detection of the corresponding extension products with different masses.
The limits of detection were 102 copies/reaction for S. pneumoniae, H.
influenzae, and N. meningitidis and 103 for M. tuberculosis. The evaluation of
the culture-positive CSF specimens from the meningitis patients provided an
overall agreement rate of 85.7% with PCR-Mass and real-time PCR. The PCR-Mass was
also able to detect the targeting pathogens from culture-negative CSF specimens
from meningitis patients receiving early antibiotic treatment. CONCLUSIONS: PCR
Mass could be used for the molecular detection of bacterial meningitis and
tuberculosis, especially when early antibiotic treatment has been administered to
the suspected patients.
PMID- 29945323
TI - Role of Paraoxonase 1 Activity and Oxidative/Antioxidative Stress Markers in
Patients with Acute Cerebral Infarction.
AB - BACKGROUND: Paraoxonase1 (PON1) is an antioxidant which confers antioxidant
properties to high-density lipoprotein (HDL) and prevents low-density lipoprotein
(LDL) oxidation. The purpose of this study was to evaluate the activities of PON1
and oxidative/antioxidative stress markers in acute cerebral infarction. METHODS:
In this study, 161 patients diagnosed with acute cerebral infarction and 161
gender- and age-matched healthy controls were recruited. Based on the
clinicoradiological profiles, the patients were further classified into two
groups: lacunar infarction group and large-artery atherosclerosis group. We
measured the individual lipid status parameters, oxidative and antioxidative
stress status parameters, and PON1 activity. RESULTS: Serum total cholesterol
(TC), low-density lipoprotein cholesterol (LDL-C), and oxidative stress
parameters in patients with acute cerebral infarction were significantly higher
than those in the normal controls (p < 0.05). High-density lipoprotein
cholesterol (HDL-C) level, PON1 activity, superoxide dismutase (SOD) activity,
and antioxidative stress parameters in patients were lower than in the normal
controls (p < 0.05). Superoxide anion (O2-), malondialdehyde (MDA), and PON1
levels in the lacunar infarction group were lower than in the large-artery
atherosclerosis group (p < 0.05). CONCLUSIONS: Oxidative stress markers and PON1
activity are sensitive indicators of acute cerebral infarction. Our findings
suggest a severely impaired antioxidative protection mechanism in these patients.
Our study provides new insights into the pathophysiological mechanisms of acute
cerebral infarction, which may also provide new therapeutic targets for ischemic
cerebrovascular diseases.
PMID- 29945324
TI - CCL22 and CCR4 Gene Polymorphisms in Myocardial Infarction: Risk Assessment of
rs4359426 and rs2228428 in Iranian Population.
AB - BACKGROUND: Myocardial infarction (MI) is an irreversible damage of myocardial
tissue caused by prolonged ischemia and hypoxia. A local hypoxia-induced
inflammation causes recruitment of leukocytes to the inflammatory site to aid
cardiac remodeling and tissue healing. Among various chemokines involved in the
process, CCL22 plays an essential role in cardiac cell migrations. In this study,
we evaluated the incidence of rs4359426 and rs2228428 SNPs in CCL22/CCR4 genes of
MI patients and studied their association with the physiology of the disease.
METHODS: Two hundred patients aged 30 - 70 years diagnosed with myocardial
infarction along with 200 agematched healthy controls were registered in the
study and their pathophysiological findings were recorded. Genotypic analysis of
rs4359426 and rs2228428 in CCL22 and CCR4 genes, respectively, were carried out
in patients using PCR-RFLP method and compared with the control group.
Successively genotyped SNPs were reviewed for their possible association with the
disease or physiological findings using Fisher's exact test. RESULTS: The
frequency of CC genotypes atboth SNPs rs4359426 and rs2228428 in CCL22 and CCR4
genes was significantly higher in MI patients compared to other genotypes.
CONCLUSIONS: Although we could not establish any direct association with the
disease due to restricted population size, it is possible that CC genotypesin
CCL22 and CCR4 could be considered as risk factors in myocardial infarction.
PMID- 29945325
TI - Requirement of ClC-3 in G0/G1 to S Phase Transition Induced by IGF-1 via ERK1/2
Cyclins Cascade in Multiple Myeloma Cells.
AB - BACKGROUND: ClC-3 is involved in the proliferation and migration of several
cancer cells. However, ClC-3 expression and its role of cell-cycle control in
multiple myeloma (MM) has not yet been investigated. METHODS: MM cells were
treated with different concentrations of IGF (30, 100, 300 ng/mL), and their
proliferation was examined by CCK-8. The effects of ClC-3 on cell cycle
progression was detected by flow cytometry. Western blot was used to analyze the
relative levels of ClC3, CD138, P21, P27, CDK, p-Erk1/2, and t-Erk1/2 protein
expression. Transfection of RPMI8226 with gpClC-3 cDNA and siRNA alters the
expression of ClC-3. RESULTS: We compared the expression of ClC-3 in primary
myeloma cells and in MM cell lines (U266 and RPMI8266) with that in normal plasma
cells (PCs) from normal subjects and found that myeloma cells from patients and
MM cell lines had significantly higher expression of ClC-3. Additionally,
silencing of ClC-3 with the small interfering RNA (siRNA) that targets human ClC
3 decreased proliferation of RPMI8226 after IGF-1 treatment and slowed cell cycle
progression from G0/G1 to S phase, which was associated with diminished
phosphorylation of ERK1/2, down-expression of cyclin E, cyclin D1 and up
regulation of p27 and p21. By contrast, overexpression of ClC-3 potentiated cell
proliferation induced by IGF-1, raised the percentage of S phase cells, enhanced
phosphorylation of ERK1/2, downregulated p27 and p21 and upregulated cyclin E and
cyclin D1. CONCLUSIONS: ClC-3 accelerated G0/G1 to S phase transition in the cell
cycle by modulating ERK1/2 kinase activity and expression of G1/S transition
related proteins, making ClC-3 an attractive therapeutic target in MM.
PMID- 29945326
TI - Correlation Between Maternal and Fetal Insulin Resistance in Pregnant Women with
Gestational Diabetes Mellitus.
AB - BACKGROUND: Offspring of mothers with gestational diabetes mellitus (GDM) are far
more likely to develop type 2 diabetes. The aim of this study was to investigate
the effect of the insulin metabolism of pregnant women with GDM in late pregnancy
on the insulin metabolism of the fetuses and their correlation. METHODS: This
study enrolled 55 pregnant women with GDM and 87 control subjects. Fasting venous
blood samples and umbilical venous blood samples (reflecting fetal metabolism)
were collected from the study subjects. All blood samples were used to evaluate
the blood glucose and insulin concentrations. The blood glucose and insulin
concentrations were measured using an automatic biochemical analyser and
radioimmunoassay, respectively. The homeostasis model assessment (HOMA) was
performed to assess the insulin resistance of mother and fetus. RESULTS: 1. The
fasting blood glucose, fasting insulin, and HOMA-IR of pregnant women in the late
pregnancy GDM group were all significantly higher than those in the control group
(fasting blood glucose: 4.70 +/- 0.11 vs. 4.11 +/- 0.05 mmol/L, p < 0.001;
fasting insulin: 44.1 +/- 6.76 vs. 25.1 +/- 3.58 uU/mL, p = 0.013; HOMA-IR: 8.92
+/- 1.25 vs. 5.39 +/- 0.83, p = 0.012); 2. The results of logistic regression
analyses showed that maternal age, pre-pregnancy body mass index (BMI), and
family history of diabetes were high-risk factors for the development of GDM in
pregnant women. 3. The insulin level and HOMA-IR in the umbilical venous blood of
the late pregnancy GDM group were both significantly higher than those in the
control group (insulin: 10.1 +/- 1.41 vs. 6.38 +/- 0.49 uU/mL, p = 0.035; HOMA
IR: 1.60 +/- 0.22 vs. 1.07 +/- 0.08, p = 0.006). 4. The umbilical venous blood
HOMA-IR in the GDM group positively correlated with the maternal HOMA-IR and
fasting insulin level. The neonatal ponderal index (PI) in the GDM group
positively correlated with the umbilical venous blood HOMA-IR and insulin level.
CONCLUSIONS: The HOMA-IR was significantly higher in the late pregnancy GDM women
and their fetuses than in the control group. In addition, fetal HOMA-IR
positively correlated to maternal HOMA-IR in late pregnancy GDM women.
PMID- 29945327
TI - Marchiafava-Bignami Disease with Cortical Involvement.
AB - BACKGROUND: Marchiafava-Bignami disease (MBD) is a neurological degenerative
disorder with a pathognomonic hallmark of symmetric demyelination in the corpus
callosum (CC). Most reported cases were chronic alcoholics and some showed
cortical lesions related to poor clinical prognosis. Herein we report a case of a
chronic alcoholic who presented with confusion and generalized weakness. METHODS:
Nerve fiber integrity and metabolic changes were evaluated with Magnetic
resonance imaging (MRI) sequences including diffusion tensor imaging (DTI) and
MRS. RESULTS: MRI revealed the typical callosal lesions of MBD with bilateral
frontoparietal cortical lesions. DTI and MRS showed both impaired myelin
integrity and axonal density in the CC. The cortical lesions partly disappeared
after intravenous administration of high-dose multivitamins and corticosteroids.
The patient regained consciousness 3 months later while dysarthria and
quadriplegia persisted. Three years later, the patient can interact occasionally
with people and the functional activities of both upper and lower limbs have no
improvement. CONCLUSIONS: To our knowledge, this is the first report of DTI
together with MRS assisting in evaluating the prognosis of MBD.
PMID- 29945329
TI - Interferon-alpha Based Individualized Treatment of a High Risk Chronic
Myelogenous Leukemia Patient Harboring T315I Mutation.
AB - BACKGROUND: T315I mutation is the most common BCR-ABL mutation and confers
resistance to all the first and second generation BCR-ABL tyrosine kinases,
including nilotinib and dasatinib. We report a high risk chronic myelogenous
leukemia (CML) patient harboring the T315I mutation treated by Interferon-alpha
(INF-alpha) solo and subsequently combined with dasatinib. METHODS: Hematological
investigation, bone marrow cytology inspection, chromosomal analysis (G-banding),
and real-time quantitative polymerase chain reaction (RQ-PCR) were performed on a
47-year-old male patient. RESULTS: After 8 months IFN-alpha monotherapy, the
patient lost the T315I mutation but acquired a new F359V mutation. After 2 months
on dasatinib and INF-alpha treatment, the patient achieved complete hematologic
response (CHR). CONCLUSIONS: IFN-alpha based combination therapy could be a
viable treatment option for CML patients harboring T315I BCR-ABL mutation.
PMID- 29945328
TI - Rivaroxaban Levels in Patients' Plasmas are Comparable by Using Two Different
Anti Xa Assay/Coagulometer Systems Calibrated with Two Different Calibrators.
AB - BACKGROUND: Rivaroxaban oral anticoagulant does not need laboratory monitoring,
but in some situations plasma level measurement is useful. The objective of this
paper was to verify analytical performance and compare two rivaroxaban calibrated
anti Xa assays/coagulometer systems with specific or other branch calibrators.
METHODS: In 59 samples drawn at trough or peak from patients taking rivaroxaban,
plasma levels were measured by HemosIL Liquid anti Xa in ACLTOP 300/500, and STA
liquid Anti Xa in TCoag Destiny Plus. HemosIL and STA rivaroxaban calibrators and
controls were used. CLSI guideline procedures EP15A3 for precision and trueness,
EP6 for linearity, and EP9 for methods comparison were used. RESULTS: Coefficient
of variation within run and total precision (CVR and CVWL respectively) of
plasmatic rivaroxaban were < 4.2 and < 4.85% and BIAS < 7.4 and < 6.5%, for
HemosIL-ACL TOP and STA-Destiny systems, respectively. Linearity verification 8 -
525 ng/mL a Deming regression for methods comparison presented R 0.963, 0.968 and
0.982, with a mean CV 13.3% when using different systems and calibrations.
CONCLUSIONS: The analytical performance of plasma rivaroxaban was acceptable in
both systems, and results from reagent/coagulometer systems are comparable even
when calibrating with different branch material.
PMID- 29945330
TI - Pentraxin-3 Predicts Short- and Mid-term Mortality in Patients with Sepsis and
Septic Shock During Intensive Care Treatment.
AB - BACKGROUND: The prognostic value of the acute phase protein Pentraxin 3 (PTX-3)
is not well evaluated in patients with septic shock, which reveal an unacceptably
high short- and long-term mortality. New Sepsis-3 definitions are not yet
implemented in most biomarker studies. Therefore, this study assesses the
prognostic value of PTX-3 for short- and mid-term mortality in patients with
sepsis or septic shock, as defined by the latest definitions, treated at a
medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients
with clinical criteria of sepsis and septic shock. Plasma levels of PTX-3,
procalcitonin (PCT) and interleukin-6 were measured on day 1, 3, and 8. All-cause
mortality was followed up to 30 days and at 6 months. RESULTS: On all three days,
PTX-3 levels were able to discriminate non-survivors from survivors at 30 days
and 6 months (AUC range: 0.59 - 0.70; 95% CI: 0.52 - 0.79; p <= 0.02). Highest
PTX-3 levels within the fourth quartiles during the first week of ICU treatment
were associated with an increased mortality rate at 30 days (OR = 7; 95% CI: 2.0
23.5; p <= 0.002) and at 6 months (OR = 5; 95% CI: 2.1 - 11.4; p <= 0.006).
Additionally, the prognostic value of PTX-3 was proven for all patients as well
as in subcohorts of patients with sepsis and septic shock, according to Sepsis-3
criteria, both in univariate and multivariate analyses for 30-day and 6-months
all-cause mortality, especially predicting all-cause mortality in septic shock
(HRs range: 1.0 - 2.9; 95% CI: 0.3 - 5.1; p <= 0.03). CONCLUSIONS: PTX-3 offers
prognostic value for the prediction of short- and mid-term all-cause mortality in
patients suffering from sepsis and septic shock according to the latest Sepsis-3
criteria.
PMID- 29945331
TI - Association Between Schizophrenia and DNA Demethylase Activity in Human
Peripheral Blood Mononuclear Cells.
AB - BACKGROUND: DNA demethylase is a crucial enzyme in the epigenetic modification
and regulation mechanisms of gene transcription. Based on previous assertions
that the pathophysiology of schizophrenia is associated with epigenetics, we
aimed to explore whether DNA demethylase activity might be related to
schizophrenia in northeast China. METHODS: We recruited 25 patients with first
episode schizophrenia and 29 normal controls from a northeast Chinese Han
population. The diagnostic criteria of schizophrenia were determined according to
diseases and related health problems, the tenth revision (ICD-10), and criteria
of mental disorders, the third revised edition (CCMD3). DNA demethylase activity
in human peripheral blood mononuclear cells (PBMCs) was measured using a DNA
demethylase activity colorimetric assay ultra kit. RESULTS: Using Student's t
test, activation of DNA demethylase and its activity were higher in schizophrenia
patients compared to healthy individuals (p < 0.001). Furthermore, the level of
DNA demethylase activity in male and female subjects with schizophrenia
significantly increased (all p < 0.05). CONCLUSIONS: Our data showed that DNA
demethylase might play a role in the pathophysiology of schizophrenia, and
individuals with higher DNA demethylase activity were susceptible to
schizophrenia in a northeast Chinese Han population. To the best of our
knowledge, this is the first time directly measured human blood samples to
examine the association between first-episode schizophrenia patients and DNA
demethylase activity, which will provide new insight to explore the effect on the
mechanism of schizophrenia.
PMID- 29945332
TI - Increased Levels of Circulating Anti-ANXA1 IgG Antibody in Patients with Non
Small Cell Lung Cancer.
AB - BACKGROUND: Our previous studies revealed that concentrations of circulating
antibodies to annexin A1 (ANXA1) were increased in non-small lung cancer (NSCLC).
This study was thus designed to replicate this initial finding with an
independent sample set. METHODS: An enzyme-linked immunosorbent assay (ELISA) was
developed in-house to examine plasma antiANXA1 IgG levels in 220 patients with
NSCLC and 200 control subjects. RESULTS: Mann-Whitney U test showed that patients
with NSCLC had significantly higher anti-ANXA1 IgG levels than control subjects
(Z = -4.02, p < 0.001); male patients appeared to mainly contribute to the
increased antibody level (Z = -3.09, p = 0.002). Receiver operating
characteristic (ROC) curve analysis showed an overall area under the ROC curve
(AUC) of 0.61 (95% CI: 0.56 - 0.67), with sensitivity of 8% against a specificity
of 95.0%. Spearman's correlation analysis failed to show a significant
correlation between the anti-ANXA1 IgG levels and the expression of three tumor
associated antigens including p53 (r = 0.156, p = 0.027), Ki67 (r = -0.048, p =
0.489), and EGFR (r = 0.02, p = 0.782). CONCLUSIONS: Increased levels of
circulating anti-ANXA1 IgG antibody may have a prognostic value for NSCLC.
PMID- 29945333
TI - Anti-E Detected in a 7-Month-Old Infant with Acute Lymphoblastic Leukemia after
Transfusion.
AB - BACKGROUND: Only a few cases of infantile anti-red blood cell alloantibody
production have been reported. METHODS: A 7-month-old girl with acute lymphoid
leukemia developed anti-E alloantibody 13 days after transfusion of E-positive
red blood cells. Antibody screening was performed before and at 2, 6, 13, 18, 27,
34, and 49 days after red blood cell transfusion. Identification test, direct
immunoglobulin test, acid elution, and dithiothreitol test were also performed.
RESULTS: Anti-E alloantibody was detected in the blood 13 days after the first
transfusion. The detected antibody was IgM and it decreased below detectable
levels within 49 days after the first transfusion. CONCLUSIONS: Follow-up testing
for the presence of post-transfusion alloantibody at appropriate times is
important, even in infants.
PMID- 29945334
TI - Validation of a New Small-Volume Sodium Citrate Collection Tube for Coagulation
Testing in Critically Ill Patients with Coagulopathy.
AB - BACKGROUND: Blood loss due to phlebotomy leads to hospital-acquired anemia and
more frequent blood transfusions that may be associated with increased risk of
morbidity and mortality in critically ill patients. Multiple blood conservation
strategies have been proposed in the context of patient blood management to
minimize blood loss. Here, we evaluated a new small-volume sodium citrate
collection tube for coagulation testing in critically ill patients. METHODS: In
46 critically adult ill patients admitted to an interdisciplinary intensive care
unit, we prospectively compared small-volume (1.8 mL) sodium citrate tubes with
the conventional (3 mL) sodium citrate tubes. The main inclusion criterium was a
proven coagulopathy (Quick < 60% and/or aPTT > 40 second) due to anticoagulation
therapy or perioperative coagulopathy. RESULTS: In total, 92 coagulation analyses
were obtained. Linear correlation analysis detected a positive relationship for 7
coagulation parameters (Prothrombin Time, r = 0.987; INR, r = 0.985; activated
Partial Thromboplastin Time, r = 0.967; Thrombin Clotting Time, r = 0.969;
Fibrinogen, r = 0.986; Antithrombin, r = 0.988; DDimer, r = 0.969). Bland-Altman
analyses revealed an absolute mean of differences of almost zero. Ninety-five
percent of data were within two standard deviations of the mean difference
suggesting interchangeability. CONCLUSIONS: As systematic deviations between
measured parameters of the two tubes were very unlikely, test results of small
volume (1.8 mL) sodium citrate tubes were equal to conventional (3 mL) sodium
citrate tubes and can be considered interchangeable. Small-volume sodium citrate
tubes reduced unnecessary diagnostic-related blood loss by about 40% and,
therefore, should be the new standard of care for routine coagulation analysis in
critically ill patients.
PMID- 29945335
TI - Request Pattern, Pre-Analytical and Analytical Conditions of Urinalysis in
Primary Care: Lessons from a One-Year Large-Scale Multicenter Study.
AB - BACKGROUND: To study the urinalysis request, pre-analytical sample conditions,
and analytical procedures. METHODS: Laboratories were asked to provide the number
of primary care urinalyses requested, and to fill out a questionnaire regarding
pre-analytical conditions and analytical procedures. RESULTS: 110 laboratories
participated in the study. 232.5 urinalyses/1,000 inhabitants were reported.
75.4% used the first morning urine. The sample reached the laboratory in less
than 2 hours in 18.8%, between 2 - 4 hours in 78.3%, and between 4 - 6 hours in
the remaining 2.9%. 92.5% combined the use of test strip and particle analysis,
and only 7.5% used the strip exclusively. All participants except one performed
automated particle analysis depending on strip results; in 16.2% the procedure
was only manual. CONCLUSIONS: Urinalysis was highly requested. There was a lack
of compliance with guidelines regarding time between micturition and analysis
that usually involved the combination of strip followed by particle analysis.
PMID- 29945336
TI - Are the Reference Ranges and Cutoff Values of Eosin-5'-Maleimide (EMA) Binding
Test for Hereditary Spherocytosis Specific for Each Age Group?
PMID- 29945337
TI - Functional muscle asymmetries and laterality in Latin American formation dancers.
AB - BACKGROUND: Despite the high popularity of Latin American dance and the specific
movement patterns characteristic of this dance discipline, studies on the
physical effects of these dance style specific movement patterns are still
lacking. OBJECTIVE: The purpose of the present study is to analyze strength level
differences and shortening of relevant muscle groups resulting from formation
dance, taking performance standard and gender into consideration. Furthermore,
the correlation between the findings of muscle function tests (MFT) and the
occurrence of lumbar spine complaints is evaluated. METHODS: A total of 66
participants (m: n= 31, f: n= 35) volunteered for this cross-sectional study
(examination group, n= 39, m: n= 19, f: n= 20). The control group consisted of n=
27 participants (m: n= 12, f: n= 15). Besides isometric maximal strength tests
(Digi Max system, mechaTronic), relevant muscle groups were examined for
shortenings (hip flexors, hamstrings). RESULTS: The male participants in dance
sport reached a significantly higher strength level in the muscles of the spine
region (p= 0.011) than the participants of the control group. The female elite
dance athletes developed a significantly higher strength level in the knee
flexors on the right side than the dancers of the advanced group (NL) (p= 0.021).
At that, muscle shortening were observed that seem to be specific to dance sport.
In addition, gender specific differences were observed both in strength levels
and in tendency to shortenings. CONCLUSION: The specific requirements profile of
Latin American formation dance seems to produce affects in the form of muscular
imbalance on both sides of the body. These differences of muscular status were
mainly observed between dance sport competitors and non-dancers rather than
between performance levels. Future investigations with higher numbers of
participants would be necessary here.
PMID- 29945338
TI - The neuropathic pain component among patients with chronic low back-radicular
pain.
AB - OBJECTIVES: Determining neuropathic pain component (NPC) among patients with
chronic low back pain-radicular pain (CLBP-RP) and the adjustment between scales
of neuropathic pain. MATERIAL-METHODS: One hundred and one patients with CLBP-RP
were included in the study. The severity of CLBP-RP was evaluated by visual
analogue scale (VAS). The Douleur Neuropathique 4 Questions (DN4) and Leeds
Assessment of Neuropathic Symptoms and Signs Scales (LANSS) were used to evaluate
the NPC. RESULTS: The mean score of CLBP-RP assessed by VAS was 80 mm. NPC was
detected a rate of 65.3% by DN4 and 40.6% by LANSS. NPC was 75.4% in females and
47.2% in males according to DN4, and 52.3% in females and 19.4% in males
according to LANSS. The female gender, occupation, and VAS scores were determined
to be significant factors contributing to presence of NPC according to logistic
regression analyses (p< 0.01, p< 0.05, p< 0.05). A medium degree accordance was
established between DN4 and LANSS scales according to kappa coefficient (Kappa =
0.532, p< 0.05). CONCLUSION: CLBP is among the diseases causing mixed type pain
accompanied by nociceptive and neuropathic pain. NPC was detected in a
considerable part of patients with radicular pain. Identifying the character of
radicular pain is significant to develop proper management strategies.
PMID- 29945339
TI - Rasterstereography versus radiography for assessing shoulder balance in
idiopathic scoliosis: A validation study relative to patients' self-image.
AB - BACKGROUND: Shoulder imbalance is a problem for scoliosis patients.
Rasterstereography uses radiation-free surface topography to follow up these
patients. Its use for assessing shoulder level has not been investigated earlier.
OBJECTIVE: This study aimed to determine the accuracy of shoulder assessment
using rasterstereography (versus radiography) and to analyze its relationship
with patients' self-image. METHODS: In a cross-sectional setting, the reliability
and validity of five rasterstereographic shoulder variables were measured in
comparison with six radiographic shoulder parameters, using correlation analysis.
The patients' self-perception was documented using the Scoliosis Research Society
22 (SRS-22) questionnaire and Trunk Appearance Perception Scale (TAPS). RESULTS:
Forty patients were included in the study. The test-retest reliability of all
rasterstereographic shoulder parameters was excellent (ICC > 0.95). The validity
was moderate in comparison with six radiographic parameters (highest coefficient:
0.582). The radiographic and rasterstereographic shoulder levels correlated with
the results in the SRS-22 questionnaire (highest coefficient: -0.463) and TAPS
(highest coefficient: 0.413). CONCLUSIONS: Rasterstereography is a reliable and
valid method for assessing shoulder level in idiopathic scoliosis. The parameters
can be recommended as a complement to radiography and clinical evaluation for
follow-up purposes. Radiographic and rasterstereographic shoulder parameters are
significantly related to patients' self-perception. Shoulder variables thus need
to be considered in scoliosis patients.
PMID- 29945340
TI - Reliability and validity of a semi-electronic tissue compliance meter to assess
muscle stiffness.
AB - BACKGROUND: Most methods assessing soft tissue stiffness are associated with high
costs and considerable technical effort. A previous study demonstrated that the
tissue compliance meter represents an affordable alternative with straightforward
handling. However, little data exists describing its measurement properties.
OBJECTIVE: The study aimed to elucidate the reliability and validity of a semi
electronic tissue compliance meter (STCM). METHODS: Tissue stiffness at the
lateral calf was examined in 34 healthy participants (24 +/- 5 yrs, 21 men).
Measurements on two consecutive days were used to estimate test-retest
reliability, day-to-day reliability and inter-rater reliability. Validity was
examined twofold. Firstly, STCM data were correlated with those of another
method, the myotonometry. Secondly, STCM measurements at different levels of
isometric contraction (M.gastrocnemius) were examined for systematic differences.
RESULTS: Intraclass correlations (ICC) revealed high test-retest reliability (ICC
0.84, 95% CI: 0.70 to 0.92; p< 0.05) and day-to-day reliability (0.84, 0.71 to
0.92; p< 0.05). Inter-rater reliability was sufficient to good (0.75, 0.56 to
0.87; p< 0.05). Cross-validation with myotonometry revealed a strong correlation
of both methods (r= 0.86; p< 0.05). Stiffness assessments during isometric
contraction demonstrated that the STCM can discriminate different force levels
(chi2= 57.1, p< 0.05). CONCLUSIONS: The STCM provides valid and reliable
measurements of tissue stiffness. Further study is needed to provide norm values
for different body regions and to reveal alterations in patients with
musculoskeletal disorders.
PMID- 29945341
TI - Effect of reclining angle on lumbar lordosis at driving posture: A radiological
evaluation.
AB - BACKGROUND: Optimal seatback angles for automobile drivers' seats have been
investigated based on comfort and back muscle activities; however, radiology
supported evidences are scarce. OBJECTIVE: The aim of this study was to evaluate
optimal range of the seatback reclining regarding torso angles for an automobile
driver's seat to preserve lumbar lordosis. METHODS: Thirty-one healthy volunteers
were recruited among five body type categories. Lateral lumbar spine X-rays were
obtained for the neutral sitting posture without seatback (reference), and with
reclining angles of 23? to 33? by 2? intervals. The Cobb angles for the L1-L4, L4
S1, and L1-S1 segments were measured. RESULTS: The Cobb angle for L4-S1 was
nearest to the reference (18.74 +/- 1.57?, mean +/- standard error mean) at
reclining angles of 29? and 31? (14.51 +/- 1.41? and 14.47 +/- 1.43?,
respectively). The Cobb angle at L4-S1 between reclining angles of 27?(12.02 +/-
1.31?) and 29? (14.51 +/- 1.41?) were significantly different (p< 0.001). Tall
men showed relatively preserved lordosis angles at all reclining angles. Fat men
and short women demonstrated prominent loss of lordosis with excessively kyphotic
L1-L4 segment. CONCLUSIONS: Reclining angles of 29? to 31? revealed to be optimal
for preserving lordosis at the L4-S1 segment. Individualized healthcare-related
guideline for driver's seat adjustment setting is necessary.
PMID- 29945342
TI - Prevalence of low back pain among athletes: A systematic review.
AB - BACKGROUND: The prevalence of low back pain (LBP) in athletes across a variety of
time frames and sports is not known. OBJECTIVES: To systematically collate and
appraise studies on the prevalence of LBP in athletes and stratify by point, one
year and life-time prevalence. METHODS: A comprehensive search was conducted in
February 2016. The following sources were individually searched: PubMed (1950 to
present), Ovid SP Medline (1950 to present), ISI (1982 to present) and Google
Scholar; Surveys were included if they aimed to report the prevalence of LBP
amongst the athletes. Two reviewers independently evaluated the methodological
quality of the studies. RESULTS: The literature search generated 4379 records.
Title and/or abstracts were reviewed by two investigators and full-texts of 201
relevant articles were selected for further evaluation. Studies were included if
they reported the prevalence of LBP in an athletic population (any level of
participation in sports and any age range) and were written in English.
Furthermore, to adequately assess the prevalence rate, studies had to report the
number of athletes with LBP as a percentage of the total number of athletes.
Studies that did not contain necessary data to calculate prevalence rate
including case reports and non-original studies were excluded and 41 studies
entered the bias assessment step. A bias assessment was applied to the
methodology of 41 studies, and 36 with low to moderate risk for bias were
included in this review. LBP in athletes was shown to have a point prevalence
ranging from 10% to 67%, a one-year prevalence ranging from 17% to 94%, and a
life-time prevalence ranging from 33% to 84%. The highest prevalence of LBP was
found among skiers, floorball players and rowers and the lowest were found in
shooters, golfers and triathletes. CONCLUSION: Like general population, LBP is
quite prevalent among athletes. There is a lack of sound data on the prevalence
and mechanism of LBP in some popular sports such as volleyball, swimming and
track and field. The lack of standardization of research methods and outcome
measurement tools are significant problems in literature. Researchers need to use
standard and internationally acceptable definitions for LBP and related
functional disability. Investigators are encouraged to conduct epidemiologic
studies, along with search for possible mechanism of LBP, by recruitment of large
sample population of the athletes who are selected through randomization of the
national population and adopt recent recommendations for a standard definition of
LBP.
PMID- 29945343
TI - Investigation of the EMG activity of erector spinae and trapezius muscles during
Islamic prayer (Salat).
AB - This study aimed to investigate the electrical activity of two muscles located at
the dorsal surface during Islamic prayer (Salat). Specifically, the
electromyography (EMG) activity of the erector spinae and trapezius muscles
during four positions observed while performing Salat, namely standing, bowing,
sitting and prostration, were investigated. Seven adult subjects with an average
age of 28.1 (+/- 3.8) years were included in the study. EMG data were obtained
from their trapezius and erector spinae muscles while the subjects maintained the
specific positions of Salat. The EMG signal was analysed using time and frequency
domain features. The results indicate that the trapezius muscle remains relaxed
during the standing and sitting positions while the erector spinae muscle remains
contracted during these two positions. Additionally, during the bowing and
prostration positions of Salat, these two muscles exhibit the opposite
activities: the trapezius muscle remains contracted while the erector spinae
muscle remains relaxed. Overall, both muscles maintain a balance in terms of
contraction and relaxation during bowing and prostration position. The
irregularity of the neuro-muscular signal might cause pain and prevent Muslims
from performing their obligatory prayer. This study will aid the accurate
understanding of how the back muscles respond in specific postures during Salat.
PMID- 29945344
TI - Downregulation of MiR-431 expression associated with lymph node metastasis and
promotes cell invasion in papillary thyroid carcinoma.
AB - BACKGROUNDS: The purpose of this study was to investigate clinical role and
functional effects of miR-431 expression in papillary thyroid carcinoma (PTC).
METHODS: Expression of miR-431 in PTC patient tissue samples and plasma samples
was examined by using qRT-PCR methods. Cell migration and invasion capacity were
evaluated using transwell assays. Western blot analysis was performed to detect
protein expression after miR-431 overexpression in PTC cells. RESULTS: We
demonstrated that miR-431 expression was lower in PTC tissues and plasma samples
compared to their corresponding controls. MiR-431 expression was particularly
lower in PTC patients with lymph node (LN) metastasis. In vitro, miR-431
overexpression significantly inhibited cell migration, invasion and EMT process
by upregulating E-cadherin and downregulating Vimentin expression. Additionally,
wedemonstrated that miR-431 overexpression suppressed Hedgehog (Hh) signaling
pathway by downregulating Gli1 expression. CONCLUSION: Our results indicated that
miR-431 could serve as a predictor for PTC patients with positive lymph node
metastasis and a potential target of PTC treatment.
PMID- 29945345
TI - Analysis of T cell receptor repertoire based on Vbeta chain in patients with
breast cancer.
AB - To find out if the T cell repertoire is efficiently and specifically provoked in
patients with breast cancer, we have investigated the clonotypes of main T cell
subsets (based on Vbeta-Chain) in tumor draining lymph nodes. CD4+ helper, CD8+
cytotoxic and (CD4+CD127dimCD25+) regulatory T cells, were negatively selected,
and isolated, from lymph node mononuclear cells of 14 untreated patients with
breast cancer. Four non-malignant patients, who underwent surgical operation,
were also recruited as the control group. Based on sequences and new nomenclature
of the T cell Receptor beta Variables (TRBVs) available in the international
ImMunoGeneTics (IMGT) database, 28 TRBV specific forward primers and two TRB
Constant region (TRBC) specific reverse primers were developed to amplify all
functional alleles. Fluorescent-labeled PCR products were then run on an ABI
PRISM 310 Genetic-Analyzer. The data was analyzed by GeneMapper software version
3.1. Clonotype analysis suggested that activated T cells are present in breast
cancer. More TRBV usage were detected among CD4+ helper and regulatory subsets,
with Gaussian-like pattern in the majority of functional TRBV families; whereas
CD8+ cytotoxic T cells showed oligoclonality in almost all TRBV families with one
or two dominant peaks in each family. Similar pattern in some of these TRBVs were
also observed among controls. Having no expression or polyclonality in the
controls, the oligoclonal pattern observed in the TRBV18, however, appears to be
specific to breast cancer patients. This phenomenon may reflect the existence of
new antigenic stimulation(s) in BC patients, preferentially activating those
clones of T cells that express TRBV18.
PMID- 29945346
TI - DDR2 overexpression in oral squamous cell carcinoma is associated to lymph node
metastasis.
AB - BACKGROUND: Discoidin domain receptors (DDRs), a collagen receptor tyrosine
kinase, play a major role in cancer progression. DDR2 has been suggested as a
prognostic marker in several cancer types; however, the correlation between DDR2
expression and clinical outcome of oral cancer patients in Taiwan population has
not been investigated. MATERIALS AND METHODS: In the present study we sought to
determine the clinical significance of Discoidin Domain Receptor Tyrosine Kinase
2 (DDR2) expression in oral squamous cell carcinoma (OSCC) patients. We examined
DDR2 expression in OSCC specimens by immunohistochemistry and then we analyzed
the association of DDR2 expression with clinicopathological factors in OSCC.
RESULTS: We divided 254 OSCC cases into two groups based on DDR2 expression
levels and compared with several clinicopathological factors and their overall
survival. The group with high DDR2 expression had significantly higher
frequencies of lymph node metastasis (P= 0.0094) and AJCC stage (P= 0.0058)
compared to the group with low DDR2 expression. Furthermore, the lymph node
metastasis oral cancer patients with high DDR2 expression had low survival rate
than low DDR2 group (P= 0.0458). CONCLUSIONS: Our data indicate that DDR2 is a
potent biomarker that can be used as an effective therapeutic target for treating
OSCC patients with lymph node metastasis.
PMID- 29945347
TI - LncRNA GACAT3 predicts poor prognosis and promotes cell proliferation in breast
cancer through regulation of miR-497/CCND2.
AB - Breast cancer is the most common malignancy in women which increases gradually
all over the world. LncRNA GACAT3 has been found to be increased in gastric
cancer and associated with tumor malignancy. However, whether GACAT3 plays a role
in the regulation of breast cancer is not known. In the present study, we found
that GACAT3 expression was increased in breast cancer tissues and cells compared
with adjacent normal tissues and normal cells. High GACAT3 expression was
correlated with the poor prognosis of breast cancer patients. GACAT3 and cyclin
D2 (CCND2) contained a binding site of miR-497. miR-497 was decreased in breast
cancer tissues and cells compared with adjacent normal tissues and normal cells.
Low miR-497 expression was correlated with the poor prognosis of breast cancer
patients. In breast cancer tissues, the expression of miR-497 was negatively
correlated with GACAT3. Downregulation of GACAT3 increased miR-497 expression.
miR-497 mimic reduced the luciferase of GACAT3 and CCND2. Anti-miR-497 reversed
the effects of GACAT3 downregulation. We also found that GACAT3 may act as a
ceRNA for miR-497, enhancing the expression of CCND2. In conclusion, GACAT3
promotes breast cancer malignancy by sponging miR-497, leading to the enhancement
of its endogenous target CCND2. These results suggest that GACAT3/miR-497/CCND2
is a potential therapeutic target and biomarker for breast cancer.
PMID- 29945348
TI - Identification of serum miR-34a as a potential biomarker in acute myeloid
leukemia.
AB - BACKGROUND: MicroRNA-34a (miR-34a), as a tumor-suppressive miRNA, has been found
to induce cell apoptosis in acute myeloid leukemia (AML). However, the diagnostic
and prognostic significance of miR-34a in AML remains largely unknown. OBJECTIVE:
We aimed to explore its associations with clinical characteristics and prognosis
of AML patients. METHODS: This study detected serum miR-34a level in 117
diagnosed AML patients and 60 control subjects by using qRT-PCR, and results were
compared to clinical features and patient outcome. Since cytogenetically-normal
AML (CN-AML) has a good uniformity of cytogenetics and provides a perfect
platform for detection of AML biomarkers, we further analyzed miR-34a expression
in 56 CN-AML subjects. RESULTS: We found that miR-34a was significantly
downregulated in AML and CN-AML patients. MiR-34a underexpression was commonly
observed in AML patients with intermediate/poor risk cytogenetic, and M5 subtype.
ROC analysis demonstrated that serum miR-34a could well identify AML/CN-AML
patients from healthy individuals. More importantly, miR-34a expression was found
negatively correlated with aggressive clinical variable, and served as an
independent prognostic indicator. In addition, AML/CN-AML patients with low miR
34a expression displayed shorter overall and recurrence free survival.
CONCLUSIONS: Altogether, miR-34a might have an application as a diagnostic and
prognostic indicator for AML patients.
PMID- 29945350
TI - Antibodies prevalence against Haemophilus influenzae type b in Jeddah population,
Saudi Arabia. I. Total antibodies.
AB - In this national comprehensive seroprevalence study, indirect ELISA test was used
to evaluate Haemophilus influenzae type b (Hib) anti-polyribosyl-ribitol
phosphate (PRP) total antibodies (IgM, IgG, IgA) in 1,003 sera samples from
routine medical check-up of healthy individuals attending the local medical
facility in Jeddah, Saudi Arabia in the period from February 2014 to January
2016. Serum anti-CPS antibodies confer immunity against invasive Hib disease. An
anti-CPS concentration of ? 0.15 MUg/mL is believed to be a serological
indication for short-term immunity protection against invasive Hib disease, while
a concentration of ? 1.0 MUg/mL is believed to be long-term protective. Results
showed higher level of anti-Hib IgG (2.41 MUg/ml average geometric mean
concentration (GMC) regardless of age and gender, followed by levels of IgM (0.91
MUg/ml) and IgA (0.34 MUg/ml), reflecting the community immunity against Hib. Low
anti-Hib level (< 0.15 MUg/ml of anti-PRP IgG) in elderly people (males aged 57
91 years and females aged 35-64 years) may indicate a need for a booster dose of
Hib vaccine to elderly people in the community. The IgG prevalence over IgM, and
IgM prevalence over IgA indicate the major role of IgG over IgM and IgA in
keeping immunity in the track against Hib. Low level of IgM and IgA comparing to
IgG may indicate the absence of Hib acute infections in the population.
PMID- 29945349
TI - Prognostic significance of peripheral blood absolute monocyte count and
lymphocyte to monocyte ratio in anaplastic large cell lymphoma.
AB - BACKGROUND: Peripheral blood absolute monocyte count (AMC) and lymphocyte to
monocyte ratio (LMR) have strong prognostic value in various forms of lymphomas.
It was found that higher AMC and lower LMR were associated with poor prognosis in
B cell lymphoma. However, their prognostic significance in systemic anaplastic
large cell lymphoma (sALCL) remained to be determined. OBJECTIVE: This study was
aimed at investigating the prognostic significance of AMC and LMR in sALCL.
METHODS: A total of 29 newly diagnosed patients with sALCL were retrospectively
included in study, prognostic significance of AMC, LMR, performance status (PS),
international prognostic index (IPI), prognostic index for T-cell lymphomas (PIT)
and other indicators were analyzed. RESULTS: Univariate analysis showed high AMC,
LMR < 2.5, PS ? 2, extranodal involvement, no response to treatment and B
symptoms predicted inferior PFS; LMR < 2.5, no response to treatment, elevated
LDH, IPI ? 3, PIT ? 2 and PS ? 2 predicted inferior OS. High AMC, PS ? 2 were
independent prognostic factors for PFS; PS ? 2, no response to treatment and
elevated LDH were independent prognostic factors for OS. CONCLUSIONS: AMC was an
independent prognostic factor for PFS in sALCL, and LMR < 2.5 also indicated poor
prognosis.
PMID- 29945351
TI - The Montreal Cognitive Assessment: Normative Data from a German-Speaking Cohort
and Comparison with International Normative Samples.
AB - BACKGROUND: The Montreal Cognitive Assessment (MoCA) is used to evaluate multiple
cognitive domains in elderly individuals. However, it is influenced by
demographic characteristics that have yet to be adequately considered. OBJECTIVE:
The aim of our study was to investigate the effects of age, education, and sex on
the MoCA total score and to provide demographically adjusted normative values for
a German-speaking population. METHODS: Subjects were recruited from a registry of
healthy volunteers. Cognitive health was defined using the Mini-Mental State
Examination (score >=27/30 points) and the Consortium to Establish a Registry for
Alzheimer's Disease-Neuropsychological Assessment Battery (total score >=85.9
points). Participants were assessed with the German version of the MoCA.
Normative values were developed based on regression analysis. Covariates were
chosen using the Predicted Residual Sums of Squares approach. RESULTS: The final
sample consisted of 283 participants (155 women, 128 men; mean (SD) age = 73.8
(5.2) years; education = 13.6 (2.9) years). Thirty-one percent of participants
scored below the original cut-off (<26/30 points). The MoCA total score was best
predicted by a regression model with age, education, and sex as covariates. Older
age, lower education, and male sex were associated with a lower MoCA total score
(p < 0.001). CONCLUSION: We developed a formula to provide demographically
adjusted standard scores for the MoCA in a German-speaking population. A
comparison with other MoCA normative studies revealed considerable differences
with respect to selection of volunteers and methods used to establish normative
data.
PMID- 29945352
TI - Nutritional Intervention to Prevent Alzheimer's Disease: Potential Benefits of
Xanthophyll Carotenoids and Omega-3 Fatty Acids Combined.
AB - BACKGROUND: A growing body of scientific evidence suggests that enrichment of
certain nutritional compounds in the brain may reduce the risk of Alzheimer's
disease (AD). OBJECTIVE: To investigate the impact of supplemental xanthophyll
carotenoids plus omega-3 fatty acids on disease progression in patients with AD.
METHODS: Three trial experiments were performed. In Trials 1 and 2 (performed on
patients with AD over an 18-month period), 12 patients (AD status at baseline: 4
mild and 8 moderate) were supplemented with a xanthophyll carotenoid only
formulation (Formulation 1; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day) and
13 patients (AD status at baseline: 2 mild, 10 moderate, and 1 severe) were
supplemented with a xanthophyll carotenoid and fish oil combination (Formulation
2; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day plus 1 g/day of fish oil
containing 430 mg docohexaenoic acid [DHA] and 90 mg eicopentaenoic acid [EPA]),
respectively. In Trial 3, 15 subjects free of AD (the control group) were
supplemented for 6 months with Formulation 1. Blood xanthophyll carotenoid
response was measured in all trials by HPLC. Omega-3 fatty acids were profiled by
direct infusion mass spectrometry. RESULTS: Xanthophyll carotenoid concentration
increases were significantly greater for Formulation 2 compared to Formulation 1
(p < 0.05), and progression of AD was less for this group (p = 0.003), with
carers reporting functional benefits in memory, sight, and mood. CONCLUSION: This
preliminary report suggests positive outcomes for patients with AD who consumed a
combination of xanthophyll carotenoids plus fish oil, but further study is
required to confirm this important observation.
PMID- 29945353
TI - Brain Metabolic, Structural, and Behavioral Pattern Learning for Early Predictive
Diagnosis of Alzheimer's Disease.
PMID- 29945355
TI - Morphology of the tongue in the tuatara, Sphenodon punctatus (Reptilia:
Lepidosauria), with comments on function and phylogeny.
AB - The morphology and histology of the tongue in Sphenodon punctatus are described
and used to infer function and to determine character state polarities in
lepidosaurs. The tongue lacks an anterior notch and is covered with filamentous
papillae, including specialized gustatory papillae containing taste buds. Lingual
glands are restricted to mucocytes covering the papillae. Three intrinsic tongue
muscles are identified and shown to be discrete fiber systems and not merely
elaborations of the M. hyoglossus. These muscles interact with a connective
tissue skeleton, particularly three septal planes, to cause changes in tongue
shape. Tongue protrusion is probably caused by hyoid protraction and contraction
of posterior genioglossus fibers; retraction by hyoid retraction, hyoglossus
contraction, and contraction of anterior genioglossus fibers. It is argued that
taste is important in prey discrimination and possibly in courtship. Vomeronasal
function is probably mediated by inhalation and not tongue movement. Insertion of
genioglossus fibers into the buccal floor is a derived feature of lepidosaur
tongues. Derived features of squamate tongues include an anterior bifurcation, a
divided genioglossus comprising medial and lateral portions, ventral transverse
and circular muscle fiber systems around the hyoglossus, and the presence of a
median septum. The tongue of the squamate family Iguanidae shares many
plesiomorphic features with Sphenodon.
PMID- 29945356
TI - Structural and functional relations of the white sturgeon alimentary canal
(Acipenser transmontanus).
AB - The anatomy and histology of the white sturgeon digestive system is described for
the adult stage and the first 36 days of posthatch development. Although the
adult gut is only 87% of standard length, absorptive surface area is effectively
increased by the thick mucosa of the postgastric gut and by lengthening of the
gut due to the presence of the spiral valve and the pyloric caecum. Modifications
of the gut of this species, relative to that of other chondrosteans, are
consistent with its durophagous feeding habits. The arrangement of the intestinal
epithelium differs from that of most fish and is organized so that absorptive
activities occur in deeper regions, whereas goblet cells dominate the lumenally
exposed epithelium. The gut develops from an intraembryonic yolk endoderm. At
conclusion of the endogenous nutrition phase the alimentary canal is similar to
the adult form and a functional gastric region is present. The anatomical
characteristics coincide with physiological data collected throughout the life
history of this species.
PMID- 29945357
TI - Proportions of mammalian-type and reptilian-type nephrons in the kidneys of two
passerine birds.
AB - We compared the proportions of mammalian-type and reptilian-type nephrons in the
kidneys of two species of passerine birds. The desert house sparrow (Passer
domesticus) is relatively well adapted for water conservation, whereas the white
crowned sparrow (Zonotrichia leucophrys) is more mesic adapted. The two species
do not differ in body mass, but the kidneys of P. domesticus are significantly
smaller than those of Z. leucophrys. Associated with its smaller size, the house
sparrow kidney has significantly fewer glomeruli (35,700 per kidney) than does
the white-crowned sparrow kidney (53,000 per kidney). The medullary cones, which
contain the loops of Henle of the mammalian-type nephrons, are significantly
longer in house sparrows than in white-crowned sparrows (2.2 vs. 1.9 mm). The
number of medullary cones, the number of nephrons per medullary cone, and, hence,
the number of mammalian-type nephrons do not differ between the two species. The
smaller number of nephrons in the kidney of the house sparrow therefore
represents a smaller number of reptilian-type nephrons. Desert house sparrows
have 18% mammalian-type nephrons, whereas white-crowned sparrows have 10%
mammaliantype nephrons. The relative reduction of reptilian-type nephrons in P.
domesticus may reduce the flow of dilute urine through the collecting ducts,
thereby permitting a greater concentration gradient to be established along the
length of the medullary cones.
PMID- 29945358
TI - Morphogenesis during molting of the setae in the statocyst sensilla of the mysid
shrimp Neomysis integer (Leach, 1814) (crustacea, mysidacea).
AB - The morphogenesis of the setae in the statocyst sensilla of Neomysis integer was
studied. Immediately before ecdysis, a new seta lies inverted between the
enveloping cells. All of the nine enveloping cells, except the first one, secrete
a well defined part of the new seta. The second, third, fourth, and fifth have a
trichogen function; the sixth has a trichogen-tormogen function; and the seventh,
eighth, and ninth enveloping cells have a tormogen function. It could not be
established whether the dendritic sheath is replaced at molt. In the second and
third enveloping cells, there is a differential secretion of cuticular material
forming the wall of the distal part of the seta. As a consequence, this wall is
not homogeneous. The possible role of this heterogeneity in the formation of the
gutter-like apical part of the seta is discussed. A mechanism is proposed by
which the pore develops at the transition between the midpart and the apical
gutter-like part. Before ecdysis, the distal segments of the sensory cells are
still connected with the wall of the old seta in the same way as during
intermolt. No degeneration is apparent in the distal segments during preparation
for the molt. These morphological findings suggest that sensitivity of the
sensilla must be maintained until the moment of the ecdysis.
PMID- 29945359
TI - Motor innervation and proprioceptors of the mouthparts in the worker honey bee,
Apis mellifera. I. Mandibular nerve.
AB - The innervation of the mandibular nerve of the worker honey bee was investigated
primarily with methylene blue vital staining. Results on the motor innervation
were compared with those of earlier work, yielding some corrections and new
findings. The nerve to the mandibular abductor muscle not only carries motor
fibers but also supplies sensory branches to the head integument and to the
presumptive proprioceptors which probably monitor movements of the proboscis. A
small neural mass which is equipped with two systems for proprioception is
situated at the point where the mandibular nerve divides into its major branches.
One system is composed of receptor muscles stretched between the anterior
tentorial arm (AT) and the mandible and multipolar cells. The other is composed
of elastic strands between AT and the apodeme of a smaller branch of the
mandibular adductor and tripolar cells. The former is stretched by mandibular
abduction and the latter by adduction. The two systems collectively are called
the mandibular muscle receptor organ. There are two groups of receptor muscles:
the outer receptor muscle, which is located outside the neural mass, and the
inner receptor muscle located within. Only the latter is innervated by multipolar
cells. Another, single, multipolar cell is attached to the surface of the tendon
of the inner receptor muscle. A further pair of bipolar-multiterminal cells
attaches to the epidermis at the extremity of the apodeme of the mandibular
adductor. One originates from the mandibular nerve and the other from the labral
nerve. Both presumably respond to the epidermal expansion caused by mandibular
abduction.
PMID- 29945360
TI - Morphometric estimates of the surface areas of the tracheal and cuticular systems
in Peripatus acacioi marcus and marcus (Onychophora).
AB - The surface areas of the tracheal and cuticular systems of Peripatus acacioi
individuals of different body weights were determined by morphometric analysis.
The results demonstrate that both surfaces increase with body weight, although
the observed increase in the surface area of the tracheal system appears to be at
a greater rate. The slopes of the two regression lines obtained are statistically
different. It is therefore suggested that the preferential route for water loss
in P. acacioi is related to the size of the animals, i.e., smaller onychophorans
would lose water mainly through the cuticle, while larger ones would lose water
through the respiratory surfaces.
PMID- 29945361
TI - Morphological evidence for a probable secretory site of the male sex pheromones
of Nauphoeta cinerea (blattaria, blaberidae). 2. electron microscope studies.
AB - Light and electron microscopy of the glandular epithelium of intersegmental
membranes between sternites three and seven and tergites two and eight of various
age groups of Nauphoeta cinerea male adults and one age group of female adults
discloses differences in the epithelia of the intersternite and intertergite. The
intersternal epithelium appears thicker, more glandular, and stratified.
Altogether, seven cell types are recognizable, six in the male and two in the
female. They are designated as types 1, 2a, 2b, 2c, 3, 4, and 5. Of these, types
1, 2a, 3, and 4 are recognizable on the sternum; types 1, 2b, and 5 on the tergum
of the mature male integuments. Types 1 and 2c are found on the sternum of mature
female. The cell types undergo morphological differentiation after adult
emergence and show different stages of secretory activity. Type 1 are squamous
cuticle-secreting cells; type 2a, 2b, and 2c are columnar-glandular and contain
electron-transparent secretory vesicles of various sizes, which increase greatly
in number and size in the 5-day-old adult males when the glands are most active.
The vesicular size and number also differ between types 2a, 2b, and 2c cells of
the same age group. The vesicles are assumed to be derived from smooth
endoplasmic reticulum. The type 2 gland cells are also provided with a secretory
end apparatus lined by cuticle and bordered by microvilli through which the
secretion is believed to be released by exocytosis. The end apparatus leads into
a cuticular ductule that opens to the surface of the cuticle as a cup-shaped
receptacle, which is more conspicuous in the male intersternite. In the active
gland cells, the mitochondria near the end apparatus are swollen and vacuolated.
Type 3 cells are seen only on the intersternum and are believed to secrete the
cuticular ductule that proceeds from the end apparatus. Type 4 cells are also
recognizable only on the male intersternum and contain closely packed, electron
dense bodies, which are most numerous in mature (5-day-old) males. Type 5 cells
with their dense cytoplasm are located basally in the intertergal epithelium. The
functional significance of type 4 and 5 cells in the males and type 2c cells in
the female is not clear. On the basis of differences in morphology, pheromone
activity, and sexual behavior, it is suggested that the pheromones secreted by
the intersternal and intertergal glands in the male are different, the former
secreting a seducin that attracts the female to the male and the latter an
"aphrodisiac" acting as a contact pheromone important in accomplishing mating.
PMID- 29945362
TI - Reevaluation of the caudal skeleton of actinopterygian fishes: I. Lepisosteus and
Amia.
AB - The centra of Lepisosteus are perichondral ossifications of arcualia (i.e.,
arcocentra), whereas those of Amia are direct perichordal ossifications (i.e.,
autocentra) that enclose the arcualia. The preural centra of Lepisosteus are
monospondylous, whereas the ural centra are formations of inter- and basidorsal
arcualia. In contrast, the preural centra of Amia are diplospondylous, whereas
preural centrum 1 (and sometimes preural centrum 2) and ural centra are
monospondylous. The ural centra of Lepisosteus are expansions of dorsal arcualia,
but those of Amia are expansions of the basiventral autocentrum. This explains
the fusion of the neural arches with the ural centra and the presence of
autogenous hypurals in Lepisosteus, in contrast to the situation in Amia in which
the compound ural neural arch (the fused ural neural arches) is free, and the
hypurals are fused to the ural centra. Lepisosteus possesses true epurals, which
are modified neural spines, whereas in Amia the "epurals" are positioned between
the neural spines like radials. Lepisosteus and Amia possess a polyural caudal
skeleton with a one-to-one relationship between ural centra and hypurals; the
number of hypurals may be reduced in adult Lepisosteus.
PMID- 29945363
TI - Sponge dermal membrane morphology: Histology of cell-mediated particle transport
during skeletal growth.
AB - The keratose demosponge, Dysidea etheria, secretes a skeletal network of
interconnecting spongin fibers and incorporates sand grains and other foreign
particles into the fibers. Previous studies showed that foreign particles
enhanced fiber growth and increased the stiffness of skeletal fibers. The present
study uses light and electron microscopy to study the mechanism of particle
incorporation. These histological observations show that particles become
engulfed into thickened regions of the mesohyl of the dermal membrane, whereupon
ameboid cells contact particles and secrete an electron dense layer of
extracellular material onto the particle surface. Within several days, particles
are moved towards primary skeletal fibers located at cone-shaped protuberances on
the sponge surface called conules. Particles accumulate at conules and are
consolidated by secretion of spongin at the growing fiber apices. The
observations suggest that coordinated migration of groups of mesohyl cells
control particle transport to conules and that patterns of cell migration are
associated with the structural organization of the dermal membrane. Particle
transport may be homologous and analogous to spicule transport in other
demosponges.
PMID- 29945364
TI - Morphology of the green livers in upstream migrants of Petromyzon marinus L.
AB - A morphological comparison was made of the green livers of male and female
lampreys (Petromyzon marinus L.) collected during the upstream (prespawning)
migration. Light and electron microscope histochemistry for iron, and both thin
sections and freeze-fracture replicas in the electron microscope, revealed some
sexual dimorphism in these livers. Ferric iron is much more abundant in the liver
of females and is present in the cytoplasmic matrix, in dense bodies, and in
vacuoles of hepatocytes. The numerous vacuoles of females may be the deposition
site of biliverdin and other bile components that would account for the darker
green coloration of the liver compared to males. Hepatocytes in females are also
characterized by prominent rough endoplasmic reticulum and Golgi apparatus that
reflect the involvement of the cells in vitellogenesis. The presence of numerous
lipid droplets in the hepatocytes of males indicates that the liver is an
important storage site for fat. The lipid droplets are associated with electron
dense deposits of unknown nature. Large gap junctions typify the parenchymal
cells of both male and female livers. Perisinusoidal and sinusoidal cells are
similar to those in the nonparenchymal region in other vertebrate livers, namely,
endothelial and Kupffer cells, lipocytes (Ito), and some granulated cells. The
relationship of lipocytes to fibrous tissue and fibrogenesis is discussed.
PMID- 29945366
TI - [Research of characteristic spectrum of Qi deficiency syndrome based on
literature mining technology].
AB - As a basic syndrome of Chinese medicine, the study of characteristic syndrome
spectrum of Qi deficiency syndrome is of great significance for the
standardization of clinical diagnosis and modern material basis research.
Suitable operators and algorithms were chosen to dig out the relationship between
diseases, syndromes, symptoms, detection indicators and etiologist from the
literature of Chinese clinical and basic research by literature mining method of
frequency statistics, association rules and complex network analysis. Moreover,
the information system of Institute of Information on Traditional Chinese
Medicine, China Academy of Chinese Medical Sciences was taken as the tools of
data mining. The objective was to study the characteristic spectrum of Qi
deficiency syndrome and to explore the characteristics of Qi deficiency syndrome.
The results showed that the syndrome of fatigue, dietary were the main factors.
The main pathogenesis of coronary heart disease, heart failure, chronic
obstructive pulmonary disease, diabetes and stroke the disease were Qi
deficiency. The clinical features of Qi deficiency syndrome were fatigue,
shortness of breath and pale tongue. The biological indicators of Qi deficiency
related were blood lipids, ECG, blood rheology, inflammatory reaction, NO, ET and
NF-kappaB signalling pathway. The Qi deficiency syndrome on the level of syndrome
spectrum was studied by the method of literature mining, which would provide
reliable characteristic guidance data for the research on the substantial basis
of Qi deficiency, the research on standard of diagnosis, establishment of
syndrome model, the study on combination of disease and syndrome and the
mechanism of prescriptions.
PMID- 29945365
TI - [Study on establishment of an animal model of Qi deficiency syndrome base on
theory of over exertion leading to Qi consumption in traditional Chinese
medicine].
AB - Based on the theory of "overexertion leading to Qi consumption", this study aimed
to compare the intervention factors of nervous and physical fatigue to establish
a rat model of Qi deficiency syndrome, moreover, the systematic evaluationsystem
was necessary with the standard of syndrome diagnosis of Qi deficiency. According
to the clinical-mimetic principle the Qi deficiency syndrome animal model is
established by the factors of sleep deprivation(SD) and exhaustive swimming(ES).
Rats were randomly divided into four groups, normal group, SD group, ES group and
compound group (exhaustion swimming complex sleep deprivation). The method of ES
was force rats to swim until the exhaustion with 5% of weight, and the SD method
by using multi-platform sleep deprivation of water environment randomly 14-16 h
daily, and the complex set by using of two methods was combined. The movement
distance, average speed, activity time and numbers into the central area were
detected by open field test, swimming exhaustion time was detected by swimming
exhaustion method, the cardiac function (LVEF, CO, FS, LVDd) was detected by
echocardiography, tongue imaging analysis and pulsedistention as the index of
tongue and pulse diagnosis, the content of ATP and ADP in serum was detected by
ELISA, the blood coagulation indexes for blood stasis syndrome as the additional.
These results indicated that independent activity, body weight and exercise
capacity were decreased significantly, the neurological function injured
significantly, heart function was decreased significantly, the tongue surface
color was pale white, and the pulse distention was decreased significantly. The
content of ATP decreased significantly and the ADP increased significantly. By
the method of four-diagnostic evaluation system to compare the factors of SD and
ES, the Qi deficiency syndrome animalmodel could be successfully established by
sleep deprivation method.
PMID- 29945367
TI - [A network pharmacology approach to explore mechanisms of Buyang Huanwu decoction
for treatment of cerebral infarction].
AB - The point of this study is to explore and investigate mechanisms of Buyang Huanwu
decoction for treatment of cerebral infarction (CI) using a network pharmacology
approach. First, TCMSP database, DrugBank database and PharmMapper server were
used and combined with oral bioavailability and drug analysis to screen the
components of Buyang Hanwu decoction and predict the potential targets. Then,
Cytoscape 3.5.1 software was used to construct compounds-targets network and the
protein-protein interaction (PPI) networks for targets of compounds and CI
related targets and merge the two PPI networks to acquire active targets.
Finally, gene ontology (GO) and KEGG pathway analysis of active targets were
carried out by DAVID online analysis tool and KOBAS 3.0 software. In total of 150
screened compounds and 232 potential targets were obtained. And in total of 208
active targets were finally determined by merging networks. Results indicated
that Buyang Huanwu decoction might have a role in treating CI by regulating some
biological processes including response to drug, aging, response to hypoxia, and
blood coagulation, and some molecular function, such as protein binding, enzyme
binding and serine-type endopeptidase activity. The mechanisms might be concerned
with PI3K-Akt signaling pathway, TNF signaling pathway, HIF-1 signaling pathway
and cAMP signaling pathway. Among them, the regulation of PI3K-Akt signaling
pathway might be one of the most crucial mechanisms.
PMID- 29945368
TI - [Quantitative proteomic research of biological basis of Buyang Huanwu decoction
therapy for cerebral infarction combined with Qi-deficiency and blood-stasis
syndrome].
AB - Chinese medicine Buyang Huanwu decoction (BYHW) is widely used in treating
cerebral infarction combined with Qi-deficiency and blood-stasis syndrome, but
the pharmacological basis is still not clear. This study aims to uncover the
biological basis of BYHW therapy for cerebral infarction combined with Qi
deficiency and blood-stasis syndrome using label-free proteomic technology. Using
Qi deficiency and blood stasis rat cerebral infarction model as the research
object, the protein expression of rat brain tissue was compared among the sham
operation group, the model group and the drug group. Quantitative analysis of the
3 groups of tissue samples detected 3 959, 3 996 and 4 055 proteins in the sham
operation group, the model group and the drug group, respectively. Take model
group as the control group, 391 proteins were identified to be upregulated or
downregulated for more than 2 folds. Biological analysis and functional
enrichment of the differentially expressed proteins revealed that BYHW may treat
cerebral infarction combined with Qi-deficiency and blood-stasis syndrome through
energy metabolism, nervous system and several signal pathways. This study
preliminarily revealed the pharmacological mechanism of BYHW at the protein
level, and provided a molecular basis for clinical treatment and traditional
Chinese medicine research on cerebral infarction combined with Qi-deficiency and
blood-stasis syndrome.
PMID- 29945369
TI - [Research progress of Gastrodiae Rhizoma machining processing, composition
analysis and in vivo metabolism].
AB - Steaming method is a traditional processing method for Gastrodiae Rhizoma(GR).
The current studies on the steaming method's mechanism of GR are mainly focused
on facilitating softening slice, destroying the beta-glycosidic bond enzymes to
reduce the decomposition of gastrodia glycosides (killing enzyme and protecting
glycosides). The researches on the processing mechanism are still incomplete,
while revealing and analyzing the active components in the body's metabolic
process are important channels and new models to clarify the mechanism of
traditional medicine processing. In order to provides a reference for the in
depth study of the processing mechanism of GR, we have reviewed the relevant
literature at home and abroad in recent years and briefly summarized the
processing, composition analysis and in vivo metabolism of GR in this study.
PMID- 29945370
TI - [Study on herbal textual evolution and flavonoids and their pharmacological of
Spatholobi Caulis].
AB - Spatholobi Caulis, the vine stem of Spatholobus suberectus and widely used in
China and Southeast Asian nations, has the effects on nourishing the blood and
promoting blood flow, regulating menstruation and relieving pain, and
invigorating the nerves. Through consulting the herbal textual and local
chronicles, we summarized the original textual research and medicinal evolution
on Spatholobi Caulis to analyze the changes of varieties in different historical
periods. Further, the major active ingredient in Spatholobi Caulis was discussed.
According to the literature to date, 60 flavonoids compounds have been isolated
and could be divided into isoflavones, dihydroflavones, flavanols,
dihydroflavonols, procyaninides, chalcones, pterocarpans, isoflavanols,
isoflavanones and aurone according to their molecular structures. These
indicative ingredients in Spatholobi Caulis showed pharmacological activities on
regulation of the blood system, anti-tumor, anti-oxidation, anti-virus, anti
bacteria and inhibition of melanin deposition. This review will provide reference
and basis for the sustainable use of resources and industry development on
Spatholobi Caulis.
PMID- 29945371
TI - [Research progress of liver disease treatment by Zhuang medicines].
AB - Liver disease has become the world's fifth deadliest disease, and its incidence
is increasing year by year. According to official data, viral hepatitis is high
incidence in China, the condition is grim that a quarter of the patients can
develop into chronic liver disease. Liver disease prevention is one of the key
research topic of medical science, searching for the natural medicines of helping
treat virus and human immunity has become the research focuses in current medical
science field. Zhuang medicines were developed from Zhuang medical theory and
practice, which are the traditional medicine used by Zhuang ancestors. The long
period of experiments and clinical researches suggest that Zhuang medicines have
therapeutic effects for liver disease and significant inhibitory effects on liver
virus. Compared with modern medical therapy in the treatment of liver disease,
Zhuang medicines therapy have more advantages in virus resistance, enzyme
activity reducing, immunity improving and disease control. This study provides
the overview of therapeutic effect and its mechanism on liver disease from active
ingredients, effective parts, extracts and compound preparation, to provide
reference for the study of Zhuang medicines' therapeutic effects on liver disease
and research progress.
PMID- 29945372
TI - [Evaluation of isolation and field effect of ginseng disease resistance and
growth-promoting bacteria].
AB - This study was aimed to isolate the strains with both disease resistance and
growth-promoting, and clarify the field application effects of the strain for
laying the further application foundation. The strains with good antagonistic
effect were isolated from the 298 strains in Panax ginseng and the soil by plate
confrontation method. The nitrogen fixation potential was verified by Ashby
medium. The Salkowski method was used to determine the ability of producing IAA.
Silicate medium screening and flame spectrophotometry was used to determine the
ability of dissolving potassium. CAS method was applied to detect the ability of
producing siderophores to determine its growth characteristics. The
morphological, physiological and biochemical and 16S rRNA sequences were used to
identify the species. The method of root irrigation was used to determine the
effects of its disease control and growth-promoting on ginseng. A strain TY15
with broad spectrum of antimicrobial effect, nitrogen fixation, potassium
dissolving and the capacity of producing IAA and siderophores was obtained by
screening. And the strain TY15 was identified as Pantoea agglomerans. The control
effect of TY15 on the disease of ginseng in the field was 68.02%, which was
equivalent to 68.94% of 30 billion per gram of beneficial microecological
bacterium agent. The fresh weight of P. ginseng treated with TY15 strain was
increased by 22.73% compared with the control group treated with water. And
finally a strain TY15 with good application prospects was obtained.
PMID- 29945373
TI - [Effects of plant growth regulators and nitrogen on germination of Epimedium
pseudowushanense after its stems and leaves reaped].
AB - In order to explore appropriate measures to promote germination after the harvest
of Epimedium pseudowushanense, 6-BA, urea, ammonium bicarbonate and GA3 were
chosen to spray on the root and rhizomes, and then the biological indicators such
as branches, leaf length, leaf width, plant height and so on, were measured in
different periods, and the contents of epimedin A, epimedin B, epimedin C and
icariin in the dry leaves were detected by HPLC. Results showed that 6-BA 90 mg.L
1(B1), 6-BA 60 mg.L-1(B2),6-BA 30 mg.L-1+urea 300 mg.L-1 (C1), 6-BA 60 mg.L
1+urea 300 mg.L-1(C2),6-BA 60 mg.L-1+ ammonium bicarbonate 300 mg.L-1(C4)
significantly increased bud germination in the early period, and the plants
quickly set up new system of photosynthesis, the branches in a month of which
were higher than the control group respectively by 165.9%, 115.76%, 103.86%,
104.50%, 81.67%.However the branches developed the next year and the dry weight
of leaves per plant in group B1 and B2 were much lower than that in control
group. The groups that use 6-BA and nitrogen at the same time reaped a good yield
of leaves even though the treatment had no significant influence on the branches
developed the next year. The dry weight of leaves of C1, C2, C4 treatments were
36.80%, 32.84%, 45.97% more than the control group respectively. Therefore, C1,
C2 and C4 treatments are the more appropriate to promote recovery after harvest.
Furthermore, different groups, except 10 mg.L-1 6-BA treatment significantly
reduced the content of epimedin C, other groups didn't have any significant
effect on the contents of such flavonoids.
PMID- 29945374
TI - [Molecular identification of cucumber mosaic virus in woad (Isatis tinctoria)
with mosaic disease in Beijing].
AB - To detect possible pathogenic virus(es) in woad (Isatis tinctoria) cultivated at
Institute of Medicinal Plant Development in Beijing, reverse transcription(RT)
PCR was performed using total RNA of symptomatic woad leaves with primers for
poty-, polero-, tobamovirus, broad bean wilt virus 2(BBWV2) and cucumber mosaic
virus (CMV). A 657 bp fragment was amplified from symptomatic woad using CMV
primers. Sequencing and BLAST analysis indicated that this fragment shared 99%
nucleotide identity and 100% amino acid identity with CMV-Vi isolate. The isolate
was named CMV-Isatis tinctorial (CMV-It). Phylogenetic analysis based on
nucleotide sequences of CP genes showed that CMV-It clustered with CMV-K and
belonged to subgroup I. To our knowledge, this is first identification of CMV in
woad by RT-PCR and the CP gene was analyzed. This work provided data for research
and control of woad mosaic disease.
PMID- 29945375
TI - [Genotype, environment and their interactions of functional components in Rheum
tanguticum].
AB - Six kinds of provenance of Rheum tanguticum collected from Qinghai province as
the test materials, which were transplanted under 3 different environments by
using complete randomized block design with three replicates. The contents of the
chemical components was determined by HPLC. This study aimed at analyzing the
effect of genotype, environment and their interactions on the 4 kinds of
functional components (phenolic acids, bianthrone, free anthraquinones and
combined anthraquinones) in 14 kinds of active components of Rh. tanguticum, in
order to provide a theoretical basis for the selection of cultivated Rh.
tanguticum in high quality producing area and excellent provenance. The
provenance trial showed that the genotype and environment influence on the effect
of all kinds of functional components in Rh. tanguticum were significant
(P<0.05). The content of phenolic acids was mainly influenced by environment, and
the other three kinds of functional components were affected by environment and
their interactions. The proportion of environment was larger. The cultivation
quality of Rh. tanguticum should give priority to environment, then choose a
provenance. Sichuan may be beneficial in accumulation of combined anthraquinones
in Rh. tanguticum, Gansu may facilitate the binding of free anthraquinone,
phenolic acids and bianthrone content. Preliminary inference based on the content
and proportion of efficacy components, T4 could be potential special medicinal
germplasm that have function of heat-clearing and detoxifying drugs and activate
blood circulation to dissipate blood stasis; T3 and T6 could all be potential
specialmedicinal germplasms that exist diarrhea attack characters. The results of
this study have certain guiding significance for the production of rhubarb
precision medicinal materials.
PMID- 29945376
TI - [Molecular cloning and characterization of CMK from Artemisia annua].
AB - Artemisinin is a preferred medicine in the treatment of malaria. In this study,
AaCMK, a key gene involved in the upstream pathway of artemisinin biosynthesis,
was cloned and characterized from Artemisia annua for the first time. The full
length cDNA of AaCMK was 1 462 bp and contained an ORF of 1 197 bp that encoded a
399-anomo-acid polypeptide. Tissue expression pattern analysis showed that AaCMK
was expressed in leaves, flowers, roots and stems, but with higher expression
level in glandular secretory trichomes. In addition, the expression of AaCMK was
markedly increased after MeJA treatment. Subcellular localization showed that the
protein encoded by AaCMK was localized in chloroplast. Overexpression of AaCMK in
Arabidopsis increased the contents of chlorophyll a, chlorophyll b and
carotenoids. These results suggest that AaCMK plays an important role in the
biosynthesis of terpenoids in A. annua and this research provids a candidate gene
that could be used for engineering the artemisinin biosynthesis.
PMID- 29945377
TI - [Complex enzyme combined with ultrasound extraction technology, physicochemical
properties and antioxidant activity of Hedysarum polysaccharides].
AB - In this study, complex enzymes combined with ultrasonic extraction technology(MC)
were used, to select optimal extraction combinations by single factor and
orthogonal test, with Hedysarum polysaccharides yield and content as the
comprehensive indexes. The components, physicochemical properties and antioxidant
activity of Hedysarum polysaccharides from complex enzyme combined with
ultrasonic extraction(HPS-MC)and the Hedysarum polysaccharides from hot water
extraction(HPS-R)were analyzed. The results showed that:complex enzymes had
significant effect on the yield and content of Hedysarum polysaccharides, and the
ultrasonic power could significantly improve the content of Hedysarum
polysaccharides. The optimum technological parameters were as follows: complex
enzyme ratio 1:1, ultrasonic power 105 W, ultrasonic time 60 min, and enzymatic
hydrolysis pH 5, achieving (14.01+/-0.64)% and (92.45+/-1.47)% respectively for
the yield and content of Polysaccharides. As compared with HPS-R, the molecular
weight, absolute viscosity and protein content of HPS-MC were decreased, while
the content of uronic acid was increased. In the antioxidant system, the
concentration of polysaccharide was within the range of 1-7 g.L-1; the
antioxidant activity of HPS-MC was higher than that of HPS-R, and HPS-MC (80%)
with the lowest molecular weight showed a significant dose effect relationship
with the increase of the experimental concentration. In conclusion, MC is a
simple, convenient, economical and environmentally friendly extraction
technology, and the Hedysarum polysaccharides extracted by this method have
obvious antioxidant activity.
PMID- 29945378
TI - [Impacts of multicomponent environment on intrinsic dissolution rate of berberine
in biopharmaceutics classification system of Chinese materia medica].
AB - To illustrate the intrinsic dissolution rate(IDR) involved in biopharmaceutics
classification system of Chinese materia medica(CMMBCS), investigate the effect
of artificial multicomponent environment on IDR of berberine, by using a non
disintegrating disk, and summarize related rules by using the obtained data.
Progressive levels design was used to investigate the effects of single component
environment (puerarin, baicalin, and glycyrrhizic acid); double-component
environment(puerarin+baicalin, puerarin+ glycyrrhizic acid, baicalin+glycyrrhizic
acid); and triple-component environment(puerarin+baicalin+glycyrrhizic acid) on
IDR of berberine, laying a foundation for further researches on the absorption
mechanism of multiple components.
PMID- 29945379
TI - [Analysis of microbial community of heat resistant microorganisms in Chinese
herbal pieces].
AB - To investigate the composition and diversity of heat resistant microorganisms in
contaminated Chinese herbal pieces. Matrix-assisted laser desorption/ionization
time of flight mass spectrometry (MALDI-TOF-MS) protein fingerprinting and 16S
rRNA high-throughput sequencing of Illumina Miseq were used to analyze the heat
resistant microbial community of 9 varieties of Chinese herbal pieces. Stem
pieces (Spatholobi Caulis, Tetrapanacis Medulla, Stachyuri Medulla) showed
highest detection rate and most species of contaminants; However fruit pieces
(Schisandrae Sphenantherae Fructus) had the lowest detection rate and least
species of contaminants; among root pieces, the detection rate and number of
contaminants species were lower in Tuber Dioscoreae Persimilis and Rehmanniae
Radix Praeparata. The heat resistant microbial community was mainly of
Bacillaceae and Paenibacillaceae, and Bacillus showed the highest detection rate
among them, followed by Brevibacillus, Paenibacillus, and Solibacillus. The rest
genus in high-throughput sequencing analysis included Enterobacter,
Brevundimonas, Leuconostoc, Methylobacterium, Dechloromonas, Pantoea, Klebsiella,
and Erwinia. There were potential risk factors in heat resistant microbial
community of Chinese herbal pieces, so we shall improve the microbial limit
standard, strictly control the pathogenic bacteria in the product, and strengthen
the supervision and management in production and circulation of Chinese herbal
pieces.
PMID- 29945380
TI - [Vinegar processing attenuates toxicity on IEC-6 cells caused by chloroform
extraction of Daphne genkwa].
AB - To screen the toxic polar fractions of Daphne genkwa, compare the toxicity of D.
genkwa on crypts epithelial cells IEC-6 before and after vinegar processing, and
preliminarily investigate the mechanism of D. genkwa vinegar processing on
toxicity reducing. The proliferation of IEC-6 cells was observed by MTT. The
levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH),
lactate dehydrogenase (LDH), as well as the enzyme activity of Na+-K+-ATPase and
Ca2+-Mg2+-ATPase were determined in IEC-6 cells to evaluate the oxidative damages
degree of IEC-6 cells. The apoptosis and cell cycle were analyzed by Flow
Cytometry. The results showed that the dichloromethane extraction was the toxic
polar fraction of D. genkwa, and after vinegar processing, the toxicity of
dichloromethane fraction was significantly reduced (P<0.01). As compared with the
blank control group, the dichloromethane fraction of D. genkwa can obviously
decrease the levels of SOD, Na+-K+-ATPase, Ca2+-Mg2+-ATPase (P<0.01) and content
of GSH, but increase the level of LDH and MDA in cell supernatant (P<0.01).
Besides, it obviously increased the early and late apoptotic rate of IEC-6 cells,
obviously decreased the proportion of G1stage cells, increased the ratio of S
stage cells and M stage cells (P<0.01). After vinegar processing, as compared
with D. genkwa groups of various doses, it can significantly increase the levels
of SOD, Na+-K+-ATPase, Ca2+-Mg2+-ATPase (P<0.01) and content of GSH, decrease the
level of LDH, MDA(P<0.01), significantly decrease the early and late apoptosis
rate of IEC-6 cells (P<0.01), increase the proportion of G1stage cells, and
decrease the ratio of S stage cells and M stage cells (P<0.01). Vinegar
processing can reduce the toxicity of dichloromethane fraction of D. genkwa, and
its mechanism may be associated with improving the activity of antioxidant
enzymes and permeability in IEC-6 cells, and decreasing the oxidative damage.
PMID- 29945381
TI - [UPLC fingerprint and multi-components determination of three processed products
of Rhizome of Curcuma wenyujin].
AB - To analyse the quality of three processed products of Rhizome of Curcuma wenyujin
by establishing an ultra performance liquid chromatography (UPLC) method for
simultaneously determining five sesquiterpene components in three processed
products of rhizome of C. wenyujin and establishing UPLC fingerprints. Component
determination was achieved on Waters ACQUITY UPLC BEH C18 column(2.1 mm*50 mm,
1.7 MUm), with acetonitrile-water as mobile phase for gradient elution. The flow
rate was 0.3 mL.min-1; column temperature was 30 degrees C; the detection
wavelength was set at 214 nm and injection volume was 1 MUL. The similarity was
analyzed with "Similarity Evaluation System for Chromatographic Fingerprint of
Chinese Materia Medica (2012.130723)", and hydrophobic cluster analysis (HCA),
principal components analysis (PCA) and orthogonal partial least squares
discriminant analysis (OPLS-DA) were conducted by using simca-p14.1 software to
investigate the differences in components among these three kinds of processed
products. The curzerene, curdione, curcumol, germacrone, furanodiene and beta
elemene showed good linearity relationship with chromatographic peak area within
the ranges of 10.8-320(r=0.999 9), 10.36-259(r=0.998 1), 10.54-263.5(r=0.999 3),
30.2-755(r=0.999 6)and 34.38-862(r=0.999 9)mg.L-1, respectively; their average
recoveries were 98.75%, 98.69%, 98.63%, 99.76% and 99.57% respectively, with RSD
of 2.67%, 1.47%, 1.29%, 2.54% and 0.87% respectively. The similarity of 30
batches of samples was larger than 0.9, indicating good consistency of the
samples. The samples can be clearly classified into three categories for HCA, PCA
and OPLS-DA pattern recognition, the differential chromatographic peak among
three processed products was found respectively. The results showed that the
pharmacology basis had changed obviously after processing of Rhizome of C.
wenyujin, so it can provide the scientific basis for rational clinical
application and establishing quality standards of three processed products of
Rhizome of curcuma wenyujin.
PMID- 29945382
TI - [Guaianolides from aerial parts of Artemisia myriantha].
AB - This study was performed to investigate the guaianolides from the aerial parts of
Artemisia myriantha. The chemical constituents were isolated by chromatographic
columns over silica gel, Sephadex LH-20, and ODS, as well as Semi-prep HPLC
methods, and their structures were identified by NMR and MS data. Ten compounds
were isolated and identified as follows: artemyriantholide E (1), tanaphillin
(2), 1beta, 10beta-epoxydehydroleucodin (3), 5-hydroxyleucodin (4),
dehydrocostuslactone (5), 3-O-methyl-iso-secotanapartholide (6), roxbughianin A
(7), dehydroleucodin (8), arglabin (9), and 8alpha-acetoxyarglabin (10). Compound
1 was a new compound, and compounds 2-7 were isolated from this plant for the
first time. Compound 3 exhibited selective cytotoxicity against human liver
cancer (Bel-7402) with IC50 value of 5.35 MUmol.L-1, and 6 against human gastric
cancer (BGC-823) with IC50 value of 2.68 MUmol.L-1, respectively.
PMID- 29945383
TI - [Chemical constituents from Fukeqianjin formula].
AB - Fukeqianjin formula, a traditional Chinese medicine compound, consists of eight
Chinese medicinal materials including roots of Moghania macrophylla, roots of
Rosa laevigata, aerial parts of Andrographis paniculata, caulis of Mahonia
fortunei, roots of Zanthoxylum dissitum, roots of Angelica sinensis, caulis of
Spatholobus suberectus, and roots of Codonopsis pilosula. The chemical
constituents from Fukeqianjin formula were studied in this paper. The compounds
were separated and purified by repeated column chromatographic methods including
silica gel, Sephadex LH-20, macroporous adsorptive resin, and reverse phase high
performance liquid chromatography. And their chemical structures were determined
by spectral data analyses. Thirty-eight compounds were obtained and identified as
Z-3-butylidenephthalide (1), Z-ligustilide (2), senkyunolide I (3), senkyunolide
H (4), vanillin (5), 7-O-methylwogonin (6), wogonin (7), panicolin (8), 19
hydroxy-8(17),13-labdadien-15,16-olide (9), andrograpanin (3,14
dideoxyandrographolide; 10), andrographolide (11), 14-deoxy-11,12
didehydroandrographolide (12), isoandrographolide (13), andrographin (2'-O
methylskullcapflavone, 14), biochanin A (15), 5-hydroxy-7,8,2',5'
tetramethoxyflavone (16), formononetin (17), daidzein (18), genistein (19),
benzoic acid (20), vanillic acid (21), trans-ferulic acid (22), salicylic acid
(23), daidzin (24), genistein-7-O-beta-D-apiofuranosyl-(1->6)-O-beta-D
glucopyranoside (25), apigenin-7-O-beta-D-glucuronide (26), andrographidin C
(27), apigenin-7-O-beta-D-(6"-methyl)glucuronide (28), neoandrographolide (29),
genistin (30), andrographiside (31), 14-deoxy-11,12-didehydroandrographiside
(32), lobetyolin (33), epicatechin (34), catechin (35), palmatine (36), berberine
(37), and jatrorrhizine (38), respectively. From the results of an individual
medicinal material studies, it can be judged that compounds 17, 19, 24 and 30 as
flavonoids came from the roots of M. macrophylla, compounds 36-38 as alkaloids
came from the caulis of M. fortunei, compounds 6-8, 14, 16, and 27 as flavonoids
as well as 9-13, 29, 31, and 32 as diterpenes came from the aerial parts of A.
paniculata, compound 5 as phenols came from the roots of Z. dissitum, compounds 1
4 as phthalides as well as compound 22 as phenylpropanoids came from the roots of
A. sinensis, compound 33 as alkynes came from the roots of C. pilosula, compounds
15, 17-19 as flavonoids as well as compound 21 as phenolic acids came from the
caulis of S. suberectus. While compounds 34 and 35 as flavanoids could come from
both the caulis of S. suberectus and roots of R. laevigata. The chemical
composition of traditional Chinese medicine compound can be tracked from the
original sources. This work provides a demonstration for the material basis study
of traditional Chinese medicine compound. Compounds 25, 26 and 28 have not so far
been isolated and identified from the above-mentioned single herb.
PMID- 29945384
TI - [Comparison of chemical constituents between Cyathula offinalis and adulterant
and their admixture by HPLC characteristic chromatogram fingerprint combined with
chemometrics].
AB - Cyathula capitate is the main adulterant of C.offinalis. According to the
literature reported, there are obvious differences in properties, taste and
pharmacological activity between C. capitate and C.offinalis. Therefore, C.
capitate can only be used as a local conventional medicine and can't be a
substitute for C. offinalis. Since the appearance of C.capitata is very similar
to the C.offinalis and the content of cyasterone also can reach the limit of the
current pharmacopoeia standard, the C.capitata is mostly sold in the form of
impersonation oradmixture, which seriously affected the safety of the clinical
medication and the development of the genuine crude drugs. In view of this, HPLC
characteristic fingerprint was used to reveal the difference of multi-ingredients
of C. offinalis, C. capitata and their admixture. According to the HPLC
chromatogram of C.offinalis, C. capitata. and their admixture, 65 different
components were obtained to set up a peak area data matrix of 26*65, which was
applied to perform the characteristic peak difference analysis, similarity
analysis, hierarchical clustering analysis HCA and principal component analysis
(PCA). Characteristic peak difference analysis showed that the characteristic
peaks of C. capitata and their admixture are more and higher respond than those
of C. offinalis. The 9 characteristic peaks were used to distinguish C. capitata,
2 of which were used to distinguish C. offinalis mixed with 5% C. capitata. UV
spectra of 9 characteristic peaks are mostly similar to the end absorption
spectra of saponins, indicating that C. capitata may contain a large amount of
saponins. By the reference fingerprint of C.offinalis established, the similarity
analysis showed that the similarity degree of C. offinalis are higher than 0.942,
while the similarity degree of C. capitata, C.offinalis mixed with 5% C. capitata
are less than 0.383 and 0.399. C.offinalis, C. capitata, C.offinalis mixed with
5% C. capitata could be obviously divided into 3 classes by HCA and PCA. These
results showed that there are obvious difference in the chemical composition of
C. offinalis, C. capitata and their admixture, which could provide evidence for
their identification.
PMID- 29945385
TI - [Transformation pathways in methanol of echinacoside, a principal effective
ingredient of Cistanches Herba].
AB - Echinacoside (ECH) is one of the active ingredients in Cistanche Herba and the
principal effective component of Memoregain(c) as well. Moreover, a new agent
namely Naoqing Zhiming tablet, derived from ECH has been licensed for clinical
trials. However, the knowledge regarding the stability of is limited, till now,
initiating a significant barrier for its further development along with the
clinical trials. Herein, we aim to in depth characterize the transformation
pattern of ECH in methanol. When ECH was stored in methanol, two primary products
(P1 and P2) could be observed in HPLC chromatogram. A home-made automated
fraction collector was configured via employing two 2-phase/6-port electronic
valves to prepare P1 and P2. Following 1H-NMR and LC-MS/MS assays, P1 and P2 were
unambiguously identified as acteoside and cistanoside A, respectively. Moreover,
the existences of cis-ECH, cis-acteoside, and cis-cistanoside A were claimed
after careful analysis of the 1H-NMR spectra of ECH, P1 and P2. Above all, the
primary transformation pathways of ECH in methanol included methylation as well
as hydrolysis, and mild transformation could also be initiated by cis/trans-
configuration transferring for the caffeoyl group. The findings obtained in
current study are envisioned to provide useful insight for the further
development of ECH and the impurity detection of Naoqing Zhiming tablet.
Moreover, the automated fraction collector configured in current study is able to
serve as a versatile tool for the collection of signals-of-interest within
phytochemical evaluations and impurity isolation.
PMID- 29945386
TI - [Systematical analysis of multiple components in drainage bear bile powder from
different sources].
AB - Bear Bile Powder contains bile acids, protein, amino acids, bilirubin and
microelements and other compounds. Among them, the bile acids are the most active
components. Currently, there are many studies on bile acids, but few reports on
other components. Therefore, the purpose of this study is to carry out a
systematical analysis of multiple components in drainage Bear Bile Powder from
different sources. Bilirubin and protein were quantified by microplate
spectrophotometer. The contents of bile acids and amino acids were determined by
liquid chromatography coupled with mass spectrometry (LC-MS). The contents of
microelements were determined by inductively coupled plasma mass spectrometry
(ICP-MS) The result indicated that among 20 batches of bear bile powder from
different sources there is high similarity (0.922-0.977). Tauroursodeoxycholic
acid (TUDCA) and taurochenodeoxycholic acid (TCDCA) were the two most abundant
components. The total contents of them were 41%-59% and met the current standard
for quality control of bear bile powder. However, significant differences were
found in their contents among samples from different sources. Besides, bilirubin,
protein, amino acids and microelements also contributed to the differentiation of
samples from different sources. The main components of bear bile powder from the
different sources were with satisfactory similarity. But bile acids, bilirubin,
protein, amino acids and microelements all contributed to the different among
samples. Our present study provided a systematical approach for the better
quality control and evaluation of bear bile powder.
PMID- 29945387
TI - [Residual status and risk assessment of forbidden and restricted pesticides of
organophosphorus in Loincerae Japonicae Flos].
AB - This paper reports the residual status of forbidden and restricted pesticides of
organophosphorus in Loincerae Japonicae Flos to provide reference for the risk
control and the formulation of maximum residue limits of the flower. A method for
the determination of residues of 23 forbidden and restricted pesticides of
organophosphorus was established, and 64 collected samples were tested. Then a
risk assessment based on the maximum residue limit was carried out. Results
showed that the detection rate of samples was 58%. 6 of 23 pesticides were
detected and the ratio was chlorpyrifos 41%, omethoate 23%, triazophos 11%,
isofenphos-methyl 6.3%, methamidophos 1.6%, isocarbophos 1.6%, respectively. And
the median of pesticide residues in the positive samples was chlorpyrifos 0.037
mg.kg-1, omethoate 0.043 mg.kg-1, triazophos 0.030 mg.kg-1, isofenphos-methyl
0.18 mg.kg-1, methamidophos 0.041 mg.kg-1, isocarbophos 0.041 mg.kg-1,
respectively. In the samples with pesticide residues, the residue amount of
methamidophos and isocarbophos was lower than the theoretical maximum residue
limit, and the residue amount of chlorpyrifos, isofenphos-methyl, triazophos were
higher than it individually, while, all the residue amount of omethoate was
higher than it. According to the assessment result of theoretical maximum residue
limit, it is suggested that relevant departments should accelerate the
formulation of the maximum residue limit standard, and strengthen the supervision
of the use of forbidden and restricted pesticides of organophosphorus in
Loincerae Japonicae Flos.
PMID- 29945388
TI - [Efficacy and mechanism of puerin I in improving disorder of glycolipid
metabolism in ApoE-/-mice].
AB - Pu-erh tea is a unique post-fermented tea processed from tender leaves of
Camellia assamica. Characteristic component puerins were produced during the
microbial fermentation process.This study focuses on the therapeutic effect and
mechanism of puerinI(P1) in Pu-erh tea on ApoE-/- mice with dyslipidemia and
diabetes. It was found that P1 could significantly decreased total cholesterol
(TC), triglyceride (TG) and fast blood glucose (FBG), and markedly improved
impaired glucose tolerance (IPGTT) and insulin sensitivity (ITT) in
hyperlipidemic and hyperglycemic ApoE-/- mice. Further experiments proved that P1
reduced FBG and plasma TG levels by inhibiting intestinal alpha-glycosidase
enzymes activity and by activating low-density lipoprotein receptor respectively.
This study confirmed the therapeutic effect and mechanism of P1 on ApoE-/- mice
with diabetes and hyperlipidemia. Based on the good efficacy of this compound, P1
could be used as a new drug to treat the disorder of glycolipid metabolism.
PMID- 29945389
TI - [Efficacy of compound Dendrobium on PI3K/AKT/eNOS signaling pathway in
hypertensive rats induced by "dietary disorders"].
AB - To observe the efficacy of compound Dendrobium on Sprague Dawley rats (SD)
hypertension model induced by "dietary disorders" and its relevant mechanism,
totally 50 SD rats were fed with high-sugar, high-fat diet and alcohol for four
weeks. According to the blood pressure after modeling, the rats were divided into
model group, valsartan group (8 mg.kg-1), low, medium and high-dose Dendrobium
candidum compound groups (1.65, 3.30, 5.00 g.kg-1), with 10 rats in each group,
and the other 10 SD rats were also taken as the normal group. After four weeks of
treatment, blood pressure was measured. Orbital blood was collected for the
determination of serum cholesterol (TC), triglycerides (TG), low-density
lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL),
calculation of atherosclerosis index (AI). Nitric acid reductase method was used
to detect serum nitric oxide (NO); the levels of serum endothelin-1 (ET-1) and
intercellular adhesion molecule-1 (ICAM-1) were measured by ELISA. The rats were
put to death after the last administration, and the protein expressions of
PI3K/AKT/eNOS in thoracic aorta of rats in each group were detected by Western
blot. The aorta was separated and stained with hematoxylin-eosin (HE) to observe
the changes in the endothelium and blood vessels in the thoracic aorta. Masson
staining was used to observe the formation of aortic collagen. The expressions of
nitric oxide synthase (eNOS) and ICAM-1 in aortic endothelial cells were observed
by immunohistochemistry. In contrast, the results show D. candidum compound can
significantly reduce the blood pressure in hypertensive rats, increase HDL-c, and
reduce AI, while increasing serum NO content, decreasing ET-1 and ICAM-1 levels
and promoting PI3K/AKT/NOS protein expressions. The lesion degree of the D.
candidum compound group was reduced, and the collagen deposition was
significantly reduced. Meanwhile, D. candidum compound can significantly increase
the expression of eNOS, and reduce the formation of ICAM-1.Therefore, D. candidum
compound has an obvious antihypertensive effect on hypertensive rats, which may
be related to the increase in PI3K/AKT/eNOS signaling pathways and NO generation,
the inhibition of the secretion of ICAM-1 and ET-1, the protection of the
vascular endothelium and the improvement of aortic disease.
PMID- 29945390
TI - [Effects of flavonoids from Pyrrosiae folium on pathological changes and
inflammatory response of diabetic nephropathy].
AB - Diabetic nephropathy (DN) is closely related to immune-mediated inflammatory
damage. Pyrrosiae folium is used commonly for the urinary system diseases with a
good efficacy, which contains abundant flavonoids (SWHT). This study was
performed to investigate the therapeutic effect of SWHT on DN and its effect on
inflammatory response. In this study, the main active components of SWHT were
identified by high performance liquid chromatography (HPLC). The results showed
that SWHT mainly contained mangiferin and isomucoside. Rat model of diabetic
nephropathy (DN) was established by feeding high glucose & high fat diet and
injecting streptozocin (STZ). Then the rats were randomly divided into control
group, DN model group, positive control group, and SWHT groups (50, 100, 200
mg.kg-1, ig). The levels of AGEs and RAGE in serum were measured by ELISA after
12 weeks of drug administration. The serum creatinine, blood urea nitrogen and
total protein levels were detected by using test kit. HE staining and
transmission electron microscopy were applied to observe the pathological changes
and structure of renal tissue. Western blot and ELISA were used to detect the
protein expression and content levels of interleukin 6 (IL-6), tumor necrosis
factor (TNF-alpha) and IL-1beta in renal tissue. Results showed that SWHT
significantly decreased serum AGEs and RAGE levels in DN rats; decreased serum
creatinine, blood urea nitrogen and total urinary protein levels, improved renal
pathological damages and reduced basement membrane thickening in DN rats. In
addition, SWHT down-regulated the protein expression levels of inflammatory
mediators IL-6, TNF-alpha and IL-1beta. The research studies indicated that SWHT
component had a potential anti-diabetic nephropathy activity, and its improvement
effect on pathological damages may be related to reducing inflammation. This
provides the basis for the scientific and rational application of P. folium, and
also provides active components for further development of Chinese medicine for
diabetic nephropathy.
PMID- 29945391
TI - [Study of isobutyrylshikonin inhibiting proliferation of colon carcinoma cells
through PI3K/Akt/m-TOR pathway].
AB - To investigate the inhibitory effect of isobutyrylshikonin on the growth of human
colon carcinoma cells in vitro and its effect on the PI3K/Akt/m-TOR pathway. MTT
assay was used to detect the inhibitory effect of different concentrations (0,
6.25, 12.5, 25, 50, 100 mg.L-1) of isobutyrylshikonin on the proliferation of
human colon carcinoma cell HT29 at 24, 48 h. CCK-8 method was used to detect the
inhibitory effect of isobutyrylshikonin on HT29, HCT116, DLD-1 and Caco-2 at 48
h. AnnexinV/propidium iodide staining was applied in detecting the apoptoticrate
of HT29 cells treated with different concentrations of isobutyrylshikonin at 24 h
and 48 h. Cycletest plus DNA was employed to analyze HT29 apoptosis and cell
cycle after 48 h treatment with isobutyrylshikonin at different concentrations.
Western blot and RT-PCR assay were used to examine the protein and mRNA
expressions of PI3K, p-PI3K, Akt, p-Akt and m-TOR. The results showed that
isobutyrylshikonin inhibited the proliferation of different human colon carcinoma
cells, and the inhibition rate was in a dose-dependent manner. Isobutyrylshikonin
induced apoptosis mainly in the early stage and blocked cells in the G0/G1 or
G2/M phase. Isobutyrylshikonin reduced the protein expressions of PI3K, p-PI3K,
Akt, p-Akt, m-TOR and the mRNA expressions of PI3K, Akt, m-TOR in a dose
dependent manner. Isobutyrylshikonin can significantly inhibit the proliferation,
induce the early apoptosis and change the cycle distribution in colon carcinoma
cells.This biological effect may be correlated with the inhibition of PI3K/AKT/m
TOR pathway.
PMID- 29945392
TI - [Effects of total flavonoids in Astragali Complanati Semen on liver lipid level
and ERalpha expression on liver in hyperlipidemia rats with kidney-Yang
deficiency pattern].
AB - Menopausal women appear lipid metabolism disorder with the ovarian function
decline and the estrogen levels decreased. Modern clinical usually use estrogen
replacement therapy and with long time application with lots of side effect
appear. Traditional Chinese medicine has more secure and effective methords,using
warming Yang drugs and methods. And the previous study proves the Chinese
medicine Astragali Complanati Semen water extraction has a good role in
regulation of blood lipids. Because of the liver is the most important organ on
regulating metabolism, therefore this study aimed to evaluate the effects of
total flavonoids in Astragali Complanati Semen(TFS)on liverlipid level and
ERalpha expressionon liver in hyperlipidemia rats with kidney-Yang deficiency
pattern to explore the substance basis and mechanism of Astragali Complanati
Semen in regulate lipid effect and clarify traditional Chinese medicine
advantages and features. This experiment uses hyperlipidemia rats with kidney
Yang deficiency pattern with bilateral ovariectomized and fed with high fat diet
for 6 weeks. And rats of sham operation group and model group rats were
intragastrilly(ig) with saline, estrogen group were intragastrilly with
estrogen(0.2 mg.kg-1). And three TFS group were intragastrilly with TFS at dose
28.5, 57, 114 mg.kg-1 for 8 weeks. At the same time, TC, TG, LDL-C,HDL-C liver
weight, liver index, uterine weight, uterine index, serum estrogen level, FSH
levels and liver pathology, liver estrogen receptor expression were detected,
weighting and calculating their organ index. The experimental results compared
with the model group, TFS 114 mg.kg-1 decreased the level of liver TG (P<0.05),
TC (P<0.001) and LDL-C (P<0.001) and increased the level of HDL-C (P<0.05).
Compared with the model group, estrogen group increased the level of blood serum
(P<0.001) and decreased the level of FSH (P<0.001). In addition, compared with
sham operation group,model group decreased the protein expression of
ERalpha(P<0.01). Compared with the model group, estrogen group increased the
protein expression of ERalpha significantly(P<0.001).TFS mid-dose group and TFS
high-dose group is increased the protein expression of ERalpha(P<0.01,
P<0.001).In a conclusion,Flavonoids is the main active ingredient of Astragali
Complanati Semen. The mechanism of it maybe is enhancing the estrogen receptor
sensitivity or the number of estrogen receptors, amplifying the signal after the
receptor conduction, which could result in lipid-lowering effect.
PMID- 29945393
TI - [Protective effect of Yiqi Huoxue decoction on kidney in diabetic GK rats].
AB - To investigate the protective effect of Yiqi Huoxue decoction on the kidney in
diabetic goto-Kaizaki (GK) rats. Eight Wistar rats were used as normal control
group. According to body weight and blood glucose, 16 GK rats were randomly
divided into model control group and Yiqi Huoxue group, with 8 rats in each
group. Drugs were administrated for 6 weeks. The rats were weighed and fasting
blood glucose (FBG) were measured weekly; the glycosylated hemoglobin (HbALc) and
24 h metabolic rate were measured at the end of third and sixth weeks, at the
same time, urine was collected to measure urinary glucose (U-GLU), urinary
creatinine (U-CREA) and total proteinuria (U-TP) by biochemical method and
calculate 24 h protein excretion rate (UAER). At the end of treatment, rats were
sacrificed in anesthesia, and creatinin (CREA), uric acid (UA) and cholesterol
(CHOL) were detected by biochemical method and glutathione peroxidase (GSH-Px)
was detected by manual method with the blood drawn from heart. Both kidneys were
taken and weighed to calculate the renal hypertrophy index. The kidneys were
placed into neutral formalin and observed under light microscope for pathological
change after Periodic Acid-Schiff (PAS) staining. The results showed that as
compared with the normal control group, FBG, HbALc, 24 h Metabolic rate, U-GLU,
UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index were
significantly increased (P<0.05) in the model group, while the body weight growth
rate, serum GSH-Px level were significantly reduced(P<0.05); in addition, renal
glomerular injury and structural changes were observed in the model group. As
compared with the model group, serum GSH-Px level was significantly increased
(P<0.05) in the Yiqi Huoxue group, While FBG, HbALc, 24 h Metabolic rate, U-GLU,
UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index were
significantly reduced (P<0.05); meanwhile, renal glomerular injury and structural
changes were improved in the Yiqi Huoxue group. The results showed that Yiqi
Huoxue decoction can significantly increase serum GSH-Px level, reduce FBG,
HbALc, 24 h metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well
as renal hypertrophy index, and improve renal pathology in diabetic GK rats.
PMID- 29945394
TI - [Effects of Huangpu Tongqiao capsule on apoptosis of Alzheimer's disease cell
model].
AB - The loss of hippocampal neurons is one of the main pathological features of
Alzheimer's disease (AD), which is related to the apoptosis of hippocampal
neurons. Huangpu Tongqiao capsule is used for the treatment of AD, but the
underlying mechanism is still unclear. This study is to investigate the mechanism
of neuroprotective effect of Huangpu Tongqiao capsule in the treatment of AD,
through observing the effect of Huangpu Tongqiao capsule containing serum on cell
injury of primary cultured hippocampal neurons induced by Abeta25-35 via
inhibiting the cell apoptosis. Primary cultured hippocampal neurons were cultured
and identified by MAP-2 immunofluorescence staining, and cell growth state was
observed by inverted microscope. The Huangpu Tongqiao capsule containing serum
was prepared using the method of serum pharmacology. MTT assays were used to
measure the optimum concentration range of Huangpu Tongqiao capsule containing
serum, and optimum Abeta concentration for establishing the AD model. After
primary cultured hippocampal neurons AD cell model was induced by Abeta25-35,
cell survival rate was detected by MTT, cell apoptosis rate was assayed by flow
cytometry, and protein expressions of Bax, Cyt C and caspase-3 were determined by
Western blot analysis. The results showed that the primary cultured hippocampal
neurons were cultured successfully, and cells grew mature at seventh days;
Compared with normal group, the survival rate of hippocampal neurons in AD cell
model group was decreased, the apoptosis rate of hippocampal neurons was
increased, and the protein expressions of Bax, Cyt C and caspase-3 were increased
(P<0.05, P<0.01); Compared with AD cell model group, the survival rate of
hippocampal neurons in Huangpu Tongqiao capsule containing serum group was
increased, the apoptosis rate of hippocampal neurons was decreased, and the
protein expressions of Bax, Cyt C and caspase-3 were decreased (P<0.05, P<0.01).
These findings suggest that Huangpu Tongqiao capsule containing serum has a
neuroprotective effect on cell injury of the primary cultured hippocampal neurons
induced by Abeta25-35, and its effect on the treatment of AD is associated with
the inhibition the apoptosis of hippocampal neurons.
PMID- 29945395
TI - [Effect of Huazhuo Jiedu formula on HIF-1alpha, VEGF, and PTEN in chronic erosive
gastritis patients with syndrome of accumulation of turbidity and toxicity].
AB - To observe the clinical efficacy of Huazhuo Jiedu formula in treating chronic
erosive gastritis (CEG) patients with syndrome of accumulation of turbidity and
toxicity, explore its mechanism by observing the changes in expression levels of
hypoxia inducible factor (HIF-1alpha), vascular endothelial growth factor (VEGF)
in serum and gastric mucosa tissues after treatment, and provide theoretical
basis for the clinical application of Huazhuo Jiedu formula in treating chronic
erosive gastritis. All 70 patient of CEG were randomly divided into control group
and treatment group, 35 cases in each group. The patients in control group
received Alatan Wuwei Wan, bid, 1 bag/time; while the patients in treatment group
were given with Huazhuo Jiedu formula, 1 dose/day. The course of the treatment
was 6 months in both groups. The changes in clinical symptoms, gastroscopic
signs, pathology and the expression levels of HIF-1alpha, VEGF, and phosphatase
and tensin homolog deleted on chromosome ten (PTEN) in serum and gastric mucosa
tissues were observed in both groups. The results showed that treatment group was
better than control group in clinical efficacy, gastroscopic efficacy and
pathological effect after treatment (P<0.05); the levels of HIF-1alpha and VEGF
in serum of treatment group were lower than those in the control group after
treatment (P<0.05), while the level of PTEN in serum of treatment group was
higher than that in the control group after treatment (P<0.05); the levels of HIF
1alpha and VEGF in gastric mucosa tissues in the treatment group were lower than
those in the control group after treatment, while the level of PTEN in gastric
mucosa tissues in treatment group was higher than that in the control group after
treatment (P<0.05), with statistically significant differences between these two
groups (P<0.05). Huazhuo Jiedu formula can improve the clinical symptoms,
gastroscopic signs and pathological conditions in CEG patients with syndrome of
accumulation of turbidity and toxicity, and the mechanism may be associated with
decreasing the expression level of HIF-1alpha, VEGF and increasing the expression
level of PTEN.
PMID- 29945396
TI - [Effect of modified Buzhong Yiqi decoction combined with pelvic floor muscle
exercise-biofeedback-electrical stimulation on early stage postpartum pelvic
floor dysfunction].
AB - To investigate the curative effect of modified Buzhong Yiqi decoction combined
with pelvic floor muscle exercise-biofeedback-electrostimulation on early
postpartum pelvic floor dysfunction disease (PFD) and its effect on the
expression of transforming growth factor (TGF-beta1), matrix metalloprotein (MMP
2), and tissue inhibitor of metalloproteinase (TIMP-2). A total of 186 PFD
patients admitted to our hospital from March 2014 to December 2016 were selected
in the study and were randomly divided into test group (n=93) and control group
(n=93). The control group received pelvic floor muscle exercises-biofeedback
electrostimulation, while the test group was additionally treated with modified
Buzhong Yiqi decoction based on the treatment in control group. Then the clinical
efficacy was compared between two groups. The results showed that vaginal
contractile electromyography (EMG), duration of vaginal constriction, dynamic
vaginal pressure and pelvic floor myoelectric activity in the test group at 1, 3
and 6 months after treatment were significantly higher than those before
treatment and the control group (P<0.05). The effective rate for urinary
incontinence was 97.14% in test group, significantly higher than 75.68% in the
control group (P<0.05). The effective rate for improvement of sexual life quality
was 96.43% in test group, significantly higher than 74.07% in control group
(P<0.05). 1, 3 and 6 months after treatment, the uterine prolapse, posterior wall
prolapse and anterior wall prolapse grade in test group was slightly lower than
that in the control group, but the difference was not statistically significant.
After treatment, the levels of TGF-beta1 and TIMP-2 in the test group were higher
than those in the control group, while the levels of MMP-2 were lower than those
in the control group (P<0.05). The results showed that modified Buzhong Yiqi
decoction combined with pelvic floor muscle exercise-biofeedback
electrostimulation can effectively relieve the clinical symptoms, promote the
body recovery and improve the quality of sexual life in PFD patients, with
remarkable advantages, so it is worthy of popularizing.
PMID- 29945397
TI - [Original materials of traditional Chinese medicinal names of "Jinchai" and
"Jinchai Shihu" based on vegetative morphology].
AB - "Jinchai Shihu" were called Jinchai and recoded in "Taishang Zhouhou Yujingfang"
of Tang Dynasty, which first clearly documented the name of Shihu in complex
Dendrobium medicines and were condiered as superior medicinal articles.
Morphological features are one of the naming principles for Chinese medicines. In
this paper, botanical origin plants under the names of "Jinchai" and "Jinchai
Shihu" were investigated. Based on documents from the local Chronicles and
historical accounts, the Chinese characters of Jinchai have the distinctive
features of gold color and two hair clasps. Moreover, the hair clasps are usually
cylindrical in shape with uniform thickness in middle and upper part, and tapers
off to the foot. And its bottom part style is simple and head part is complex.
Thus we speculated the herbal "Jinchai" and "Jinchai Shihu" should have similar
morphologic features as Chinese characters of Jinchai, including golden color and
hairpin shape of stems without braches, short and solid sterm. After comparing
the dried vegetative morphology of 10 common medicinal Dendrobium species, we
suggested that of Dendrobium flexicaule matches well with the morphological
features from historical herbal records.
PMID- 29945399
TI - [Thoughts of omics research on quality formation in Dao-di herbs].
AB - Dao-di herbs have been recognized as "quality models" with a firmly stable
status. The formation of Dao-di herbs quality is involved from the genetic
inheritance on the molecular level to the metabolic phenotype of final products,
and the full material-based biosynthetic pathway remains unknown. In recent
years, an increasing variety of omics technologies has provided new methods and
ideas for the analysis of complex life systems and are suitable for explanation
of quality formation in Dao-di herbs as well. In order to alleviate the scarcity
of natural resources and offer scientific guidance of transplanting varieties,
achievements of omics in the aspects of Dao-di herbs from genetics to
phenotyping, the biosynthetic pathway of secondary metabolites, the interaction
with human body and the new methods of quality evaluation have been summarized.
It will be a fundamental work for protection and utilization of Chinese medicine
resources.
PMID- 29945398
TI - [Progress in researches on pathogens, epidemiology and integrated control of
diseases on Salvia miltiorrhiza in China].
AB - Danshen (Salvia miltiorrhiza) is a perennial herbal plant as a bulk commodity of
traditional Chinese medicinal material. With the growing market demand, the
planting scale of Danshen has been fast enlarged. The occurance of diseases on
Danshen has become as a major threaten of its production. Root diseases are most
devastated on Danshen. Rootrot is the most important disease, and Fusarium wilt
comes second. Leaf spot occurs most on aerial part of Danshen. In the Danshen
industry, the chemical control is most commonly used, with biological agents as
supplements. This review summarized the symptom, pathogen, epidemiology, and
control method of 7 diseases on Danshen (rootrot, Fusarium wilt, southern blight,
root knot nematode, leaf spot, leaf red and virus diseases), providing guidelines
for disease diagnostics, pathogen isolation and identification, proper pesticide
application and integrated control.
PMID- 29945400
TI - [Precise application of Traditional Chinese Medicine in minimally-invasive
techniques].
AB - The miminally-invasive techniques of traditional Chinese medicine(TCM) uses
different types of acupuncture needles to treat diseased locations with special
techniques. These techniques include different methods of insertion and closed
incision (press cutting, sliding cutting, scrape cutting, etc.). This needling
technique is based on the traditional Chinese medicine theories of Pi
Bu(cutaneous), Jing Jin(sinew), Jing Luo(meridian), Wu Ti(five body structure
components) and Zang Fu(organ system). Commonly used needles include: needle Dao,
needle with edge, Pi needle, Shui needle, Ren needle, Gou needle, Chang Yuan
needle, Bo needle and so on. The principle of this minimally-invasive technique
of TCM is to achieve the greatest healing benefit with the least amount of
anatomical and physiological intervention. This will result in the highest
standard of health care with the lowest rehabilitative need and burden of care.
In the past 20 years, through the collaborative research of several hundred
hospitals across China, we systemically reviewed the best minimally invasive
technique of TCM and the first line treatments for selective conditions. In 2013,
the Department of Medical Affairs of the State Administration of Traditional
Chinese Medicine created "Traditional Chinese Medicine Technical Manual"(General
Version) and released it nationwide, its contents include: (1)Minimally invasive
scar tissue release. 1Suitable for Bi and pain syndromes of neck, shoulder,
waist, buttocks and extremities. 2Degeneration causes local hypertrophy and
inflammation, creating local tissue adhesion. 3There are two kind incision
methods-press cutting and slide cutting. (2)Minimally invasive fascial tension
release. 1Suitable for localized fascial tension caused by trauma, overuse, or
wind-cold-dampness, leading to compensatory hyperplasia. 2Long term high-stress
stimulation to local fascia creates compensatory hyperplasia, Ashi points, and
tissue texture changes (cords, nodules, masses). 3According to the different
structural features of the needles, there are two incision methods: penetrating
from the outside to the inside and pulling from inside to outside. (3)Minimally
invasive decompression technique. 1Suitable for internal pressure changes within
organ cavities caused by trauma, degeneration, inflammation, such as compartment
syndrome, bone marrow edema, increased intraluminal pressure in the bone marrow.
2According to the different tissues, it is categorized into soft tissue
decompression, and bone decompression. (4)Minimally invasive orthopedic surgery.
Applicable to some postural, developmental deformity correction, mainly through
the dynamic balance method and/or static balance method. (5)Minimally invasive
dissection. Suitable for fractures, tendons injury caused by deep soft tissue
adhesion. (6)Minimally invasive separation. 1Suitable for cutaneous, sinew
regions, superficial adhesions due to lesions, and local post-operative incision
adhesions. 2According to the structure of the needle tip, the methods are divided
into sharp separation and blunt dissection. (7)Minimally invasive sustained
pressure technique. 1Suitable for neuromuscular dysfunction which causes
JING(spasm) syndrome and WEI(atrophy) syndrome. 2The needle is applied with
sustained pressure, without penetrating select tissue surface. This includes:
nerve root sustained pressure technique; peripheral nerve sustained pressure
technique; muscle sustained pressure technique; fascial contact procedure;
cutaneous sustained pressure technique.(8)Minimally invasive insertion technique.
1Suitable for systemic regulation to treat disease. 2Different organs are
connected to different layers of tissue. Therefore, to treat specific conditions,
specific tissues must be targeted. 3For example, back Shu points are used to
treat vertigo from cervical spine issues, and spinal degeneration associated
digestion issue. 4The internal organs can be regulated by the pathways that runs
along the different layers of tissue. The types of stimulation include: meridian
acupoint stimulation; cutaneous stimulation; fascia stimulation; mucle
stimulation; periosteum stimulation. The clinical application of these techniques
has enriched the drug-free therapies of traditional Chinese medicine and achieved
excellent outcomes, but at the same time it also raises an important question.
How can we apply these minimally invasive techniques to clinical practice so it
can be safe and effective? In addition, how can practitioners, individually and
further develop their understanding of this minimally invasive technique
progressive manner? We make the following recommendations. (1)Clear diagnosis and
precise application. Any approach has specific indications and choosing the
correct technique comes from a comprehensive understanding of its advantages and
disadvantages. Moreover, the accurate application of the technique depends the
expertise of the practitioner. Through systematic review and clinical
observation, we formulated the First Line Treatment, the Second Line Treatment,
and the Third Line Treatment for specific conditions. Using the information
gathered from research, practitioners can decide on which point is appropriate to
use based on the stage of disease progression. For example, common conditions
like the nerve ending tension pain(i.e. cutaneous nerve entrapment syndrome) is
caused by stress concentration. There are two types of treatment for this
condition: 1Change in the response to stress state (i.e.non-invasive approach
such as manual therapy and physiotherapy). 2Change in state of surrounding
environment (i.e. invasive approach such as Pi Needle). Before tissue texture
changes to pain point, cord, nodules, the former approach is effective. Once
tissue texture changes, the latter approach is First Line Treatment.
(2)Systematic training and disease progression training. The minimally invasive
techniques of traditional Chinese medicine can treat many kinds of disease. To
ensure its safety, organization, progressive development, practitioners are
trained systematically and manage their treatment approach through disease
hierarchy. Moreover, this technique should be conducted according to its
technical difficulty, operating conditions, and expertise of the practitioner.
The application of minimally invasive techniques of traditional Chinese medicine
does not depend on the hospitals' administration system or the regulatory college
of medical professionals. The minimally invasive techniques of TCM should be
taught from easy to difficult, simple to complicated, and requires gradual
progression by the practitioners. Eventually, the minimally invasive techniques
of TCM's diagnostic and treatment protocol can be created. These protocols are
currently available for reference: 1Forming diagnosis and differential diagnosis
for the conditions below requires expert diagnostic and application skills:
cerebral palsy; cervical vertigo; cervical headache; cervical precordial pain;
other spine-related diseases. 2The requirements for the diagnosis and
differential diagnosis of such techniques are relatively high, and special
training is required for the practitioner who performs this technique. The
conditions below uses minimally invasive orthopedic surgery and dissection: scar
contracture deformity; congenital developmental malformations; cervical Bi
syndrome; shoulder pain syndrome; knee Bi-syndrome; low back pain; cervical
spondylosis; lumbar disc herniation; avascular necrosis of the femoral head;
ankylosing spondylitis. 3There are no special requirements for the diagnosis and
differential diagnosis of such techniques, and special training is required for
the practitioner who performs this technique. The technical content is mainly
decompression and scar tissue release. a)Muscle strain diseases: levator
scapulae, splenius capitis, splenius cervicis, supraspinatus, infraspinatus,
teres minor, teres major, serratus posterior superior, serratus posterior
inferior, piriformis, gluteus maximus, gluteus medius, and gluteus minimus,
erector spinae. b)Joint degenerative disorders: frozen shoulder, tennis elbow,
tenosynovitis, knee osteoarthritis, and plantar fascitis. c)JING-JIN PI-BU pain
syndrome (cutaneous nerve entrapment syndrome): occipital great nerve entrapment
syndrome, occipital small nerve entrapment syndrome, great auricular nerve
entrapment syndrome, suprascapular nerve entrapment syndrome, transverse
cutaneous nerve of neck entrapment syndrome. (3)People-centred practice. The most
attractive feature of the minimally invasive techniques of TCM is that they do
not rely on expensive medical equipment and operating conditions. The key to
applying this technique is the practitioners' technique, skill, and expertise.
The necessary conditions required to successfully apply this technique is
1practitioner understands disease progression and diagnosis; 2practitioners'
skill in applying technique. We require patient-centered approach, which uses
evidence based approach as the focus. We aim to seek the truth from facts, to
understand the comprehensive picture, to include pertinent details, to be
observant, to be goal oriented, from one to another, from outside to inside, from
top to the bottom, compare right from left, through active movement and passive
movements and weight-bearing movements, and assisted passive movements to
determine instantaneous centre to diagnose stress concentration points. The
operating technique is based on the response of patient's tissues to this
technique. We must pay attention to diagnosis through palpation: layers,
structure, texture, deformity, dislocation, movement characteristic, rhythmic
changes. To achieve SHOU MO XIN HUI WU WEI: position, quantify, quantity, timing,
and pattern. Accurate grasp of timeliness and dose efficiency. Can distinguish
between local or systemic effects of treatment. Through comprehensive judgment of
hands feeling, acupuncture needle feeling, and inspiration, to achieve the
precious treatment requirements as indicated by the "Huangdi Neijing.Suwen":
"Puncture the bone without damaging tendons, and puncture tendons without
damaging muscles, puncture the muscle without damaging pulse, puncture pulse
without damaging skin, puncture skin without damaging muscle. Puncture muscle
without damage tendons, puncture tendons without damaging bone... Puncture bone
without damaging tendons and it means the needle passes through the tendons and
arrives at the bone and work on the bone. Puncture tendons without damaging
muscles, and it means the needle passes through the muscles and arrives close to
the tendon. Puncture the muscle without damaging pulse and it means the needle
passes the pulse and does not touch the muscle. Puncture pulse without damaging
skin and it means, the needle passes through the skin without penetrating pulse.
Puncture skin without damaging muscle and it means, the disease is in the skin
and the needles insert into skin but does not damage muscle. Puncture muscle
without damage tendons, and it means, the needle passes through the muscle and
arrive on the tendon. Puncture tendons without damaging bone."
PMID- 29945402
TI - [Clinical results of needle Dao for the treatment of subacromial impingement
syndrome].
AB - OBJECTIVE: To study the clinical results of needle Dao for the treatment of
subacromial impingement syndrome. METHODS: From September 2013 to August 2014, 90
patients with subacromial impingement syndrome were treated, including 61 females
and 29 males, with the average age of (55.21+/-8.30) years old(ranged, 45 to 65
years old), and mean course of disease (3.49+/-2.98) months (ranged, 4 weeks to 7
months). Twenty-six patients had pains in left shoulder, and 64 patients had
pains in right shoulder. Under local anesthesia, needle Dao was performed to
release the pain point at the lower edge of the acromion and the subacromial
adhesion. By observing the abduction of shoulder joint, anterior flexion and
lifting, internal rotation and external rotation, shoulder pain score, the number
of cases cured, markedly effective, effective and ineffective after treatment
were counted, and the curative effect of needle Dao for the treatment of
subacromial impingement syndrome was evaluated. RESULTS: All the patients
completed the treatment successfully without obvious adverse reactions. All the
patients were followed up for more than 12 months. The visual analogue scale(VAS)
decreased from preoperative 7.72+/-5.42 to postoperative 1.35+/-0.78(t=15.89,
P<0.01). The Constant score at the 12th month after operation increased from
preoperative 58.89+/-15.63 to 83.17+/-19.11(t=28.48, P<0.01). Overall efficacy
evaluation was that, 46 cases were cured, 33 cases were markedly effective, 11
cases were effective, and 0 cases were invalid. CONCLUSIONS: The advantage of
needle Dao in the treatment of subacromial impingement syndrome is the minimally
invasive treatment of the underlying lesions. The disadvantage is that it can not
deal with the impact caused by bone abnormalities.
PMID- 29945401
TI - [A case-control study on the treatment of carpal tunnel syndrome with needle
Dao].
AB - OBJECTIVE: To study clinical effects of needle Dao for the treatment of carpal
tunnel syndrome. METHODS: From July 2014 to December 2016, 60 patients with
carpal tunnel syndrome were divided into two groups: needle Dao treatment
group(treatment group), and brace and medicine treatment group(control group), 30
cases in each group. There were 8 males and 22 females in the treatment group,
with an average age of (49.38+/-7.43) years old. There were 7 males and 23
females in the control group, with an average age of (50.23+/-8.71) years old.
There were no statistically significant differences between two groups before
treatment in age, sex, course of disease, sensory nerve conduction velocity
(SCV), sensory nerve action potential (SNAP), and distal motor latency(DML). The
patients in the treatment group were treated with needle Dao for 1 to 2 times,
while the patients in the control group were given celecoxib, vitamin B1 and
vitamin B12, with the brace fixed. After treatment, the changes of SCV, SNAP and
DML in two groups were observed. RESULTS: After treatment, the SCV were (48.63+/
7.33) m/s and (41.24+/-6.15) m/s in treatment group and control group separately,
the SNAP were (9.89+/-3.71) m/s and (8.22+/-2.19) m/s, and the DML were(5.11+/
2.28) m/s and (6.13+/-2.23) m/s. The SCV, SNAP and DML after treatment were
better than those before treatment(P<0.05). And the results of SCV, SNAP and DML
of patients in the treatment group were better than those of patients in the
control group(P<0.001). CONCLUSIONS: Needle Dao can effectively improve the
overall treatment efficiency of patients with carpal tunnel syndrome and reduce
the symptoms of patients, which is feasible and suitable to use in clinical.
PMID- 29945403
TI - [Case-control study on the treatment of heel spur syndrome with modified
stretching manipulation combined with needle Dao loosing].
AB - OBJECTIVE: To study the clinical effects of modified plantar fascia stretching
manipulation combined with needle Dao loosing in the treatment of heel spur
syndrome. METHODS: From September 2010 to September 2015, 115 patients diagnosed
as heel spur syndrome were divided into two groups: treatment group and control
group. There were 58 patients in the treatment group, including 21 males and 37
females, ranging in age from 26 to 73 years old, with the course of disease from
6 to 51 months. The patients in the treatment group were treated with modified
plantar fascia stretching manipulation combined with needle Dao loosing. There
were 57 patients in the control group, including 22 males and 35 females, ranging
in age from 31 to 75 years old, with the course of disease from 7 to 58 months.
The patients in the control group were treated with traditonal stretching
manipulation combined with needle Dao loosing. The NRS scores of heel pain were
evaluated at the 1st week, 1 and 3 months after treatment; and the clinical
effects of the two groups were evaluated with the Foot and Ankle Ability
Measure(FAAM) scale evaluation system. RESULTS: The numerical rating scale(NRS)
scores were 3.89+/-0.96 and 2.46+/-0.95 in the treatment group 1 month and 3
months after treatment, which were superior to 4.52+/-1.21 and 4.73+/-1.11 in the
control group; and the FAAM rates in the treatment group were (3.89+/-0.96)%
and(2.46+/-0.95)% separately 1 month and 3 months after treatment, which were
better than (4.52+/-1.21)% and (4.73+/-1.11)% in the control group. The total
curative effects of the treatment group were better than that of the control
group. CONCLUSIONS: The modified plantar fascia stretching manipulation combined
with needle Dao loosing can locate the traction point, which has a significant
effect on the patients with heel spur syndrome. Compared with traditonal
stretching manipulation combined with needle Dao loosing, this modified
mainpulation combined with needle knife loosing has better medium to-long term
effects.
PMID- 29945404
TI - [Case-control study on Pi needle for the treatment of the cutaneous nerve
entrapment low back pain].
AB - OBJECTIVE: To explore a safe and effective method for the treatment of low back
pain in the cutaneous nerve, and to clarify the indication of Pi needle to treat
it. METHODS: From January 2003 to December 2004, 278 patients with cutaneous
nerve entrapment low back pain were divided into two groups: Pi needle group and
electrical stimulation group. In the Pi needle group, there were 68 males and 70
females, ranging in age from 20 to 60 years old, with an average of(41.92+/
10.88)years old. In the electrical stimulation group, there were 68 males and 72
females, ranging in age from 18 to 60 years old, with an average of(41.44+/
10.47) years old. The pain, tenderness and soft tissue tension of the two groups
were measured and compared before and after treatment. RESULTS: All of the
selected cases were qualified. No suspension, culling and shedding cases occurred
in either group. In Pi needle group, visual analog scale(VAS) of pain decreased
from 8.78+/-1.52 before treatment to 1.33+/-1.33 after treatment;and in
electrical stimulation group, VASof pain decreased from 8.59+/-1.76 before
treatment to 5.20+/-2.64 after treatment;and the VAS of pain of the Pi needle
group was lower than that of the electrical stimulation group. In Pi needle
group, VAS of tenderness decreased from 9.12+/-1.24 before treatment to 1.60+/
1.36 after treatment;and in electrical stimulation group, VAS of pain decreased
from 8.79+/-1.60 before treatment to 5.34+/-2.60 after treatment;and the VAS of
pain of the Pi needle group was lower than that of the electrical stimulation
group. CONCLUSIONS: Once tissue texture changes to pain point, cord, nodules, Pi
needle is the first line treatment for the cutaneous nerve entrapment low back
pain.
PMID- 29945405
TI - [Minimally invasive treatment of Dupuytren's contracture by Pi needle
percutaneous multi-segmental fasciotomy].
AB - OBJECTIVE: To investigate the clinical efficacy of Pi needle percutaneous multi
segmental fasciotomy as a minimally invasive treatment for Dupuytren's
contracture. METHODS: Sixteen patients(25 fingers: 4 middle fingers, 12 ring
fingers, 9 little fingers) were involved in the study, including 11 males and 5
females. There were 2 cases on both hands and 14 cases of single hand disease,
including 8 cases of left hand and 6 cases of right hand. The age ranged from 48
to 79 years old, with a mean age of 58.5 years old. The duration of the disease
ranged from 1 to 15 years, with a mean time of 5.5 years. There were 12 cases of
physical labor, 4 cases of non physical labor, with no family history of palmar
fascial contracture. There were 9 cases of tobacco and alcohol addicts, 6 cases
with hypertension history, and 3 cases of diabetes mellitus. According to
Meyerding classification, 1 case was stage 0, 1 case was stage I, 10 cases were
stage II, 4 cases were stage III and 0 case was stage IV. The postoperative
function of Dupuytren's contracture patients was evaluated according to Adam
efficacy evaluation criteria. RESULTS: The time of incision healing time ranged
from 7 to 14 days, 10 days on average. The 3 fingers incision skin cracked 3 to 4
mm during the loosening process, and 14 days after dressing changed, no skin
necrosis and wound infection complication occurred. After treatment, fascia
contracture of 24 fingers completely or almost disappeared. Limited extension of
metacarpophalangeal joint and interphalangeal joint ranged from 0 to 10 degrees,
22 fingers showed normal function of finger extension, 2 fingers had more than
75% elongation function, and 1 finger recurred. According to the evaluation of
Adam evaluable standard of curative effect on the postoperative function of
Dupuytrens's contracture: 22 fingers got an excellent result, 2 fingers good and
1 finger recurred. The patients were satisfied with the results of the treatment.
CONCLUSIONS: Pi needle percutaneous multi-segmental fasciotomy for the treatment
of Dupuytren's contracture is a simple, minimally invasive and effective method.
PMID- 29945406
TI - [Treatment of 60 patients with temporomandibular joint dysfunction by
manipulative reduction of cervical vertebrae combined with Pi needle release].
AB - OBJECTIVE: To evaluate the clinical effects of manipulative reduction of cervical
vertebrae combined with Pi needle release for the treatment of temporomandibular
joint dysfunction. METHODS: From March 2012 to May 2017, 60 patients with
temporomandibular joint dysfunction were treated by manipulative reduction of
cervical vertebrae with Pi needle release, including 26 males and 34 females,
ranging in age from 18 to 60 years old, with an average of 32.5 years old. The
courses of the disease ranged from 1 week to 5 years, with a mean duration of 3
months. The patients were followed up before and after treatment by maximum
active opening of temporomandibular joint, joint clicking and comparison of
visual analogue scale (VAS) pain scores. RESULTS: All 60 patients were followed
up, and the duration ranged from 6 to 24 months, with an average of 12 months.
The maximum active opening of temporomandibular joint increased from(1.99+/-0.47)
cm before treatment to(3.17+/-0.19) cm. The joint clicking decreased from 100%
before treatment to(27.33+/-13.51)% after treatment. The VAS score decreased from
4.73+/-0.67 before treatment to 1.80+/-0.53 after treatment. CONCLUSIONS:
Treatment of temporomandibular joint dysfunction by manipulative reduction of
cervical vertebrae combined with Pi needle release has such advantages as easy
operation, obvious curative effect, short course of treatment, which is an
effective method for the treatment of temporomandibular joint dysfunction.
PMID- 29945407
TI - [Logistic regression analysis on the outcome predictive factors of ruptured
lumbar disc herniation].
AB - OBJECTIVE: To investigate the outcome predictive factors of ruptured lumbar disc
herniation after conservative treatment. METHODS: From June 2009 to June 2016,
147 patients with ruptured lumbar intervertebral disc herniation were treated
with conservative treatment in the orthopedics department of Suzhou Traditional
Chinese Medicine Hospital for clinical efficacy and MRI follow-up. Multivariate
Logistic regression analysis(Stepwise regression method)was used to analyze the
relationship between the 11 categorical variables and absorptivity of
protrusions: sex(X1), age(X2), course of disease(X3) , the rate of
protrusion(X4), the Komori type(X5), the MSU type(X6), the Iwabuchi type(X7), the
Pfirrmann grade(X8), the Modic change on adjacent vertebrae(X9), spinal canal
morphology(X10), the Schizas types of cauda equina sedimentation sign(X11).
RESULTS: A total of 64 cases of prominent reabsorption among all cases followed
up (absorption rate>=30%), accounting for 43.5%. The reabsorption of protrusions
is more likely to occur in patients with a duration of less than 1 year(P=0.006),
MSU type 3 (P=0.001), Iwabuchi type 1 or 5 (P=0.000), the Schizas type of cauda
equina sedimentation sign A or B(P=0.004). Regression equation Y=
10.363+1.916X3+1.446X4-1.445X5+2.070X6+4.679X7+1.125X9+1.023X10+2.223X11. Such
factors as age, gender, Pfirrmann classification and spinal canal morphology had
no significant effect on reabsorption of protrusions. CONCLUSIONS: Ruptured
lumbar disc herniation can be reabsorbed after nonoperative treatment. And the
reabsorption of protrusions is more likely to occur in patients with a duration
of less than 1 year, MSU type 3, Iwabuchi type 1 or 5, the Schizas type of cauda
equina sedimentation sign A or B, which can be used as the key reference factors
for predicting the outcome of the projections.
PMID- 29945408
TI - [Establishment of grading model of knee osteoarthritis based on clinical research
system].
AB - OBJECTIVE: The factors influencing the grade of knee osteoarthritis were screened
by ordered Logistic regression analysis. The classification model of knee
osteoarthritis was established, which provided tool for the evaluation of
clinical classification of knee osteoarthritis. METHODS: A total of 753 cases of
knee osteoarthritis from Wangjing Hospital, China Academy of Chinese Medical
Sciences were treated with single factor and multivariate Logistic regression
analysis from September 18, 2014 to April 26, 2016. The model formula was
constructed and evaluated. RESULTS: In this study, it was found that 13 factors
associated with knee osteoarthritis grading. Old age, obesity, long course of
disease, recurrence, lower limb deformity, quadriceps muscle atrophy, WOMAC
index, TCM syndrome score, VAS score and grading degree were positively
correlated. One knee pain, limited pain range, knee activity and grading degree
were negatively correlated. The knee osteoarthritis grading model was constructed
and the evaluation test was effective(Training set AUC=0.860, test set
AUC=0.879). CONCLUSIONS: In this study, a classification model of knee
osteoarthritis was established which has a good ability to predict the
classification of knee osteoarthritis under preliminary evaluation.
PMID- 29945409
TI - [Case-control study on a new Kirschner wire tension band with hole in the
treatment of adult olecranon fractures in adults].
AB - OBJECTIVE: To compare the efficacy of Kirschner wire tension band with hole and
common Kirschner wire tension band in the treatment of olecranon fractures in
adults, so as to guide the selection of clinical surgical procedures. METHODS:
From July 2011 to October 2015, a total of 49 patients with olecranon fractures
underwent open reduction and fixation with Kirschner wire tension band, which
were retrospectively analyzed. Of the 49 patients, 21 patients(group A) were
treated with Kirschner wire tension band with hole, including 12 males and 9
females, with an average age of(37.6 +/-8.2) years old;28 patients(group B) were
treated with common Kirschner wire, including 18 males and 10 females, with an
average age of(38.9+/-7.3) years old. There were no statistically significant
differences between the two groups in general data. The differences of operative
duration, frequency of radiation, fracture healing time, complications and
postoperative elbow function scores between the two groups were observed and
analyzed by parallel statistical analysis. RESULTS: In group A, the operative
duration was(60.4+/-10.7) min, the average number of radiation times was (12.5+/
2.9); in group B, the operative duration was (62.3+/-11.8) min, and the average
radiation times was(13.7+/-3.8); there was no significant difference in operative
time and radiation times between the two groups (P >0.05). In group A, the
fracture healing time was (13.2+/-2.6) weeks without K-wire migration, skin
irritation and other complications; and fracture healing time in group B
was(14.6+/-1.8) weeks with complications(K-wire migration in 6 cases, skin
irritation in 7 cases, internal fixation failure in 2 cases);the fracture healing
time of group A was shorter than that in group B. Evaluation of elbow joint
function in two groups of patients after operation showed that in group A, pain
score was 41.0+/-3.5, movement function score was 18.0+/-2.1, stability score was
9.0+/-0.8, daily activities score was 18.0+/-4.3, the total average score was
87.0+/-7.8; and in group B, the pain score was 39.0+/-5.6, movement function
score was 17.0+/-3.2, the stability score was 8.0+/-2.4, daily activities score
was 16.0+/-5.2, the total average score was 83.0+/-10.7. There were no
statistically significant in the scores between the two groups. CONCLUSIONS:
Compared with ordinary Kirschner wire, the treatment of olecranon fracture with
Kirschner tension band with hole can shorten the time of fracture healing,
significantly reduce the occurrence of complications, and do not affect the
recovery of postoperative function, which is suitable for clinical use.
PMID- 29945410
TI - [NSAIDs combined with radiotherapy to prevent heterotopic ossification after
total hip arthroplasty].
AB - OBJECTIVE: To investigate the preventive effects and differences of NSAIDs
combined with radiotherapy, NSAIDs and radiotherapy for heterotopic
ossification(HO) after total hip arthroplasty(THA). METHODS: From February 2015
to July 2016, 168 hips undergoing primary THA were divided into group A, B and C,
and 163 patients were followed up (54 cases and 54 hips in group A, 55 cases and
55 hips in group B, 54 cases and 54 hips in group C). Among group A, 5 hips were
primary osteoarthritis, 37 hips were secondary osteoarthritis due to avascular
necrosis of the femoral head, 12 hips were secondary osteoarthritis due to
acetabular dysplasia. Patients in group A received oral celecoxib (0.2 g, 2 times
a day) for 2 weeks after operation. Among group B, 6 hips were primary
osteoarthritis, 32 hips were secondary osteoarthritis due to avascular necrosis
of the femoral head, 17 hips were secondary osteoarthritis due to acetabular
dysplasia, all of which in group B were treated with preoperative single 7 Gy
radiotherapy. Among group C, 5 hips were primary osteoarthritis, 35 hips were
secondary osteoarthritis due to avascular necrosis of the femoral head, 14 hips
were secondary osteoarthritis due to acetabular dysplasia. Patients in group C
were treated with preoperative radiotherapy and celecoxib after operation. The
side effects of gastrointestinal reactions were observed after operation, and the
heterotopic ossification was evaluated by pelvic anterior and posterior X-ray
(Brooker grading). RESULTS: The mean clinical and radiological follow-up was 21
months(12 to 30 months). In group A, 54 hips were followed up with 7 hips with
heterotopic ossification, including 5 hips of Brooker I and 2 hips of Brooker II.
In group B, 55 hips were successfully followed up, with 8 hips of heterotopic
ossification occurred, including 6 hips of Brooker I, 2 hips of Brooker II. In
group C, 54 hips were successfully followed up, with 5 hips of heterotopic
ossification occurred , including 4 hips of Brooker I, 1 hip of Brooker II. There
was no significant difference in efficacy among 3 groups (chi2=0.743, P=0.690) by
chi-square test. The prevalence of side effects were as following: in group A,
there were 6 hips with side effects;in group B, there were 6 hips with side
effects;in group C, there were 7 hips with side effects. There was also no
significant difference in side effects among 3 groups (chi2=0.135, P=0.935).
CONCLUSIONS: The combined-therapy group has lower prevalence of HO than the
NSAIDs group or radiotherapy group, but the statistical difference between them
is not significant. NSAIDs is still the first choice to prevent HO after THA.
PMID- 29945411
TI - [CT assisted goat lumbar vertebrae anatomical measurement and comparison with
human lumbar vertebrae].
AB - OBJECTIVE: To study the anatomical measurement of goat lumbar vertebrae and to
compare with human lumbar vertebrae, so as to build the foundation for
establishing animal models of lumbar prosthesis. METHODS: The anatomical
parameters of the vertebral body, pedicle and intervertebral disc in the fresh
lumbar vertebrae of Boer goat and the lumbar vertebrae of healthy adults were
collected by computer aided software Mimics16.0, and the anatomical
characteristics of the two lumbar vertebrae were compared with the statistical
software. RESULTS: The anterior vertebral body height(VBHa) of goat lumbar was
less than the middle vertebral body height(VBHm), which was less than the
posterior vertebral body height(VBHp), and the maximum values were (38.7+/-2.9),
(40.1+/-2.6) and (40.7+/-2.7) mm respectively. Its endplate width was greater
than its depth, with the whole shaped like a heart or a kidney. The cranial
endplate of goats was convex while the caudal endplate was depressed and the
depression was small, with a maximum value of (1.6+/-0.6) mm. The pedicle height
of goats increased from L11 to L with the maximum of (30.5+/-1.9) mm; its pedicle
width and angle increased firstly and then decreased with the increase of
vertebra level and the minimum values were (6.7+/-0.4) mm and(45.9+/-2.6) degrees
respectively. The anterior intervertebral disc height was larger than the middle
which was larger than the posterior and all varied slightly with the changes of
intervertebral spaces; the height and width of intervertebral foramen separately
waved at (12.9+/-0.3) to (14.3+/-1.0) mm and (5.7+/-1.0) to (6.7+/-0.9) mm. The
comparative results showed that the vertebral body height, pedicle height and
angle of goats were greater than those of humans (P<0.05) while the width and
depth of the endplate, the intervertebral disc height, and etc. were
significantly smaller than those of humans (P<0.05). In addition, some
structures, such as the height of pedicle and intervertebral disc, also showed
different changing laws with the increase of vertebra level. CONCLUSIONS:
Although there are similarities in goat lumbar spine in some aspects, such as
endplate and foramen foramen, there are still many differences in many aspects.
Understanding the anatomical characteristics of goat lumbar vertebrae and the
difference between goat and human is of great guiding significance for the
research of goat prosthesis and related technology.
PMID- 29945412
TI - [Expression characteristics of Piezo1 protein in stress models of human
degenerative chondrocytes].
AB - OBJECTIVE: To explore the expression characteristics of new mechanosensitive ion
channel Piezo1 protein in stress models of human degenerative chondrocytes.
METHODS: The stress stimulation model of human degenerative chondrocytes in vitro
was constructed. Multi-channel cell stretch stress loading system FX-4000T was
used to treat chondrocytes. According to the results of pre-test, the loading
frequency of 0.5 Hz and the cell elongation of 20% were loaded. According to cell
processing time, it was divided into 0 h, 2 h, 12 h, 24 h and 48 h mechanical
stress group. The RT-PCR and Western-blot were used to test the expression of the
Piezo1, also the Laser scanning confocal microscope (LSCM) was used to test the
intensity of the fluorescence of the Piezo1. RESULTS: (1)The result of the RT-PCR
showed that the expression of the Piezo1 in the 2 h group was higher than the 0 h
group(F=13.917, q=0.037 1, P<0.05). The expression of the piezo1 in the 24 h
group was the highest. While the expression of the piezo1 in the 48 h group was
lower than the expression of the piezo1 in the 24 h group(F=13.917, q=0.049 5,
P<0.05). (2)The result of the Western-blot showed that the 2 h group was higher
than the 0 h group(F=19.341, q=0.037 1, P<0.05). The expression of the 24 h had
the highest expression which was higher than the 48 h group(F=19.341, q=0.017 7,
P<0.05). (3)The Piezo1 protein was extensively expressed in the cytoplasm and
nucleus of the nucleus pulposus cells. And with the increase of stress processing
time, the fluorescence intensity of the protein also increased. CONCLUSIONS: In
human degeneration cartilage cells, the new mechanio sensitive ion channel Piezo1
protein has a trace expression. After loading periodic mechanical tensile force,
the expression of Piezo1 protein increases with time dependence.
PMID- 29945413
TI - [Causes and strategies for postoperative bone nonunion after bone transport of
lower limb bone of chronic osteomyelitis with bone defect].
AB - OBJECTIVE: To explore causes and strategies for postoperative bone nonunion after
bone transport of lower limb bone of chronic osteomyelitis with bone defect.
METHODS: From June 2012 to December 2015, clinical data of 38 patients with lower
limb bone of chronic osteomyelitis with bone defect were retrospectively
analyzed, including 23 males and 15 females aged from 20 to 56 years old with an
average of 36.5 years old; 5 cases occurred on 5 femoral osteomyelitis and 33
cases were tibial;the time from injury to bone transport ranged from 2 to 19
months with an average of 7.4 months; the distance of bone defect ranged from 4
to 12 cm with an average of 7.3 cm. Bone transport were performed at 1 week later
after operations, and transport directions were from near-end to far-end for 30
cases, from far-end to near-end for 3 cases and bidirectional transport for
another 5 cases. The alignment and transport speed were adjusted and weight
bearing was encouraged. Regular follow-up was performed and X-ray films were
taken to observe complications such as poor mineralization in transport gaps,
nonunion of docking sites, and recurrent fracture. Paley scoring was used to
evaluate clinical effects. RESULTS: All patients were followed up for 12 to 36
months with an average of 23.1 months. No recurrence of osteomyelitis, but
multiple complications associated with poor bony healing occurred. In the process
of bone transport, 3 cases occurred poor mineralization in transport gaps, 17
cases occurred ununion of docking sites, 5 cases suffered fracture gap, 1 case
occurred fracture without remove of external fixation, and 4 cases occurred
facture after remove of external fixation. The time of taken fixation ranged from
9 to 27 months with an average of 16.3 months; index of external fixation ranged
from 1.7 to 2.7 months/cm with an average of 2.24 months/cm. According to Paley's
scoring, bony results showed 12 cases excellent, 16 good, 3 moderate and 7
poor;and functional results showed 14 cases excellent, 18 good, 3 moderate and 3
poor. CONCLUSIONS: Bone transport technique could effectively solve clinical
problems of long bone osteomyelitis with bone defect. However, long treatment
period influence prognosis. Therefore, indications should be chosen strict, and
operations should be precise and accurate, also monitored across whole process
and followed up in time. Doctors should be actively guide corresponding
prevention strategies.
PMID- 29945414
TI - [Chondroid lipoma: a case report of the left buttock].
PMID- 29945415
TI - [Revision of failed anterior cruciate ligament reconstruction with allogeneic
tendon in knee joint: a case report and literature review].
PMID- 29945416
TI - [Dynesys and posterior decompression and fusion internal fixation for the
treatment of lumbar degenerative diseases: a systematic review].
AB - OBJECTIVE: Meta analysis was used to evaluate the efficacy and safety of Dynesys
and posterior decompression and fusion internal fixation for lumbar degenerative
diseases. METHODS: The computer was used to retrieve the Cochrane library,
Medline, Embase, CNKI, Wanfang database and Chinese biomedical literature
database; and the references and main Chinese and English Department of
orthopedics journals were manually searched. All the prospective or retrospective
comparative studies on the clinical efficacy and safety of Dynesys and posterior
decompression and fusion internal fixation were collected, so as to evaluate the
methodological quality of the study and to extract the data. The RevMan 5.2
software provided by Cochrane collaboration was used for systematic evaluation.
RESULTS: A total of 9 clinical studies were included, including 3 prospective
randomized controlled trials(RCT) and 6 retrospective controlled observational
studies, which included 692 patients, with 336 cases in Dynesys group, and 356
cases in posterior decompression and fusion internal fixation (PLIF) group. The
results showed that compared with PLIF, Dynesys system significantly decreased
operation time(P<0.01), intraoperative blood loss (P<0.01). Both Dynesys and PLIF
groups experienced improved ODI and back/leg pain VAS scores at final follow-up,
and no statistically significant difference was noted according to the two
surgical procedures(P>0.05). Dynesys could remain the range of motion (ROM) of
surgical segments with less increased ROM of adjacent segments compared with that
of PLIF group(P<0.01). Regarding the disc height of surgical segments, no
statistically significant difference was noted according to the two
groups(P>0.05), but postoperative complications incidence rate in PLIF group was
higher than that in Dynesys group (P<0.05). CONCLUSIONS: Both Dynesys system and
PLIF can improve clinical outcomes of lumbar degenerative diseases effectively.
Compared with PLIF, Dynesys could remain the range of motion(ROM) of surgical
segments with less increased ROM of adjacent segments and lower complication
incidence rate. But the ability to prevent adjacent segments degeneration needs
more RCTs with long-term follow-up to confirm.
PMID- 29945417
TI - [Application of MRI in diagnosis of transient dislocation of patella].
AB - OBJECTIVE: To explore the diagnostic value of MRI in the transient dislocation of
the patella. METHODS: The DR and MRI data of 35 patients with acute patellar
transient dislocation from January 2015 to December 2017 were retrospectively
analyzed, including 12 males and 23 females, ranging in age from 10 to 23 years
old, with an average of 17 years old. The differences between DR and MRI
diagnosis and surgical or discharge diagnosis were compared, and the difference
between them in diagnosis of knee anatomical position, bone injury, signs and
soft tissue injury were compared. The R statistical software WiLcoxon signed rank
test (WiLcoxon signed rank test) was used for statistical analysis. RESULTS: All
35 MRI findings were completely consistent with postoperative or discharge
diagnosis. According to MRI, 7 cases of high patella and 7 cases of patella
subluxation were diagnosed. According to DR, 7 cases of high patella and 0 cases
of patella subluxation were diagnosed. Fourteen dislocations were diagnosed by
MRI and 7 dislocations were diagnosed by DR. There was statistically significant
difference between the two methods in the diagnosis of abnormal position of
patella(v=10, P<0.05). Total 112 cases of bone injuries were diagnosed by MRI,
and 0 was diagnosed by DR. There was statistically significant difference between
the two methods in the diagnosis of bone injuries(v=16, P<0.05). Total 43 cases
of soft tissue injuries were diagnosed by MRI, and 0 was diagnosed by DR. There
was statistically significant difference between the two methods in the diagnosis
of soft tissue injuries (v=21, P<0.05). Total 35 cases of hydrops of the knee
joint were diagnosed by MRI, and 30 were diagnosed by DR. There was statistically
significant difference between the two methods in the diagnosis of hydrops of the
knee joint(v=32, P>0.05). CONCLUSIONS: MRI is superior to DR in the diagnosis of
acute temporal bone dislocation. MRI should be used as the first choice for
imaging diagnosis of acute temporal bone dislocation. It can avoid missed
diagnosis and misdiagnosis.
PMID- 29945418
TI - [Progress on the treatment of terrible triad injury of elbow joint].
AB - As to terrible triad injury of elbow joint, because of the complexity of the
surrounding anatomy of the elbow joint, the limited biomechanical study, the
difficult treatments, and the poor prognosis, the choice of the treatment scheme
is still controversial. This article summarizes the anatomy, injury mechanism,
surgical treatment and prognosis of elbow joint by retrieving a large number of
references. Currently, there are various surgical treatments for triad injury of
elbow joint, but due to individual differences, the clinical efficacy is mostly
uncertain. In the treatment of triad injury of elbow joint, most orthopedics
doctors still choose the lateral surgical approach to fix the coronary fracture,
repair or replace the radial head, routinely repair the lateral collateral
ligament, and not recommend to repair the medial collateral ligament, so it still
remains to be discussed.
PMID- 29945419
TI - [Effect of surgical scope on postoperative fibrosis of knee joints].
AB - Knee arthrofibrosis is a common complication after surgery, which is one of the
key factors affecting the surgical outcome. It often causes the decrease of joint
activity, chronic arthralgia, degeneration of cartilage tissues and joint disuse
change, which seriously affects the daily life of the patients. How to reduce the
occurrence of knee arthrofibrosis is the key to improve the expected effect of
surgery, which is also an important problem to solve in clinical medicine; with
our team's previous and recent research, we found that the degree of knee
arthrofibrosis is closely related to the rang of the surgical. The use of
minimally invasive and arthroscopic treatment can reduce the damage to synovial,
cartilage and fat pad tissue, at the same time, combining with early
postoperative rehabilitation training is the future effective prevention of
postoperative arthrofibrosis of knee.
PMID- 29945420
TI - Effects of Antiplatelet Agents on Bleeding after Endoscopic Resection of Gastric
Tumor.
PMID- 29945421
TI - Long-Term Clinical Efficacy and Safety of Endoscopic Submucosal Dissection for
Early Gastric Cancer in Korea.
PMID- 29945422
TI - Does Estrogen Contribute to the Esophageal Barrier Function in Women?
PMID- 29945424
TI - The "Bilio-Papillary Z Line": Proposal for a Novel Quality Indicator of Direct
Cholangioscopy.
PMID- 29945423
TI - An Elevated Platelet Count Increases the Risk of Relapse in Ulcerative Colitis
Patients with Mucosal Healing.
AB - Background/Aims: Although mucosal healing (MH) has been considered a treatment
goal for patients with ulcerative colitis (UC), the risk factors predictive of
relapse in patients who achieve MH are unknown. Because the platelet count has
been shown to be a marker of inflammation in inflammatory bowel diseases, this
study aimed to assess whether the platelet count could predict relapse in UC
patients with MH. Methods: A prospective observational study was performed. UC
patients with MH were consecutively enrolled in the study and monitored for at
least 2 years or until relapse. The correlation between the incidence of relapse
and the platelet count at the time of study enrollment was examined. Results: In
total, 43 patients were enrolled, and 14 patients (33%) relapsed. The median
platelet count at the time of enrollment in the patients who relapsed
significantly differed from that in the patients who did not relapse
(27.2*104/MUL vs 23.8*104/MUL, respectively; p=0.016). A platelet count
>25.0*104/MUL was a significant risk factor for relapse based on a multivariate
analysis (hazard ratio, 4.85; 95% confidence interval, 1.07 to 25.28), and
according to the Kaplan-Meier analysis, this cutoff could identify patients
susceptible to relapse (p=0.041, log-rank test). Conclusions: The platelet count
could be used as a predictor of relapse in UC patients with MH.
PMID- 29945425
TI - Alterations in Serum BDNF and GDNF Levels after 12 Weeks of Antidepressant
Treatment in Female Outpatients with Major Depressive Disorder.
AB - Objective: Some clinical studies have found alterations in the levels of serum
brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic
factor (GDNF) after applying antidepressant treatment in patients with major
depressive disorder (MDD). We evaluated the serum BDNF and GDNF levels before and
after 12 weeks of antidepressant treatment in MDD outpatients. Methods: Serum
BDNF and GDNF levels were measured in 23 female MDD outpatients at baseline and
after 12 weeks of treatment. The severity of depression was measured with the
Hamilton Depression Rating Scale-17 (HAMD-17). Remission of MDD to the treatment
was defined as a posttreatment HAMD-17 score of <7. Results: Among MDD patients,
19 (82.6%) subjects were in mild to moderate depression. The whole MDD patients
had significantly higher serum BDNF and GDNF levels at baseline than those after
12 weeks of antidepressant treatment. The baseline serum BDNF and GDNF levels did
not significantly between the remission and nonremission groups. The significant
alteration in both BDNF and GDNF levels after antidepressant treatment were
observed in patients with remission. Conclusion: The present study suggests that
the baseline serum BDNF and GDNF levels are higher than the posttreatment levels
in some mild-to-moderate MDD outpatients and the significant alteration in BDNF
and GDNF level after treatment were observed in patients with remission.
PMID- 29945426
TI - Psychiatric Consultations at an Emergency Department in a Metropolitan University
Hospital in Northern Japan.
AB - Many patients with mental disorders visit emergency departments (EDs). However,
the majority of these patients do not receive psychiatric assessment. In the
present study, we investigated the detailed proportion of patients with mental
disorders visiting an urban ED in the largest northern city in Japan. A
retrospective chart review study was performed at a University Hospital from
January 2012 to December 2015. The reasons for psychiatric consultations made by
ED staff, and the primary psychiatric diagnoses were investigated. Among all
living patients, 20% of them received consultations. The most common reason for
consultation was suicide attempt followed by agitation or insomnia. Of all
diagnoses, organic mental disorder was the most frequent and the mean age was
significantly higher than the other diagnostic groups. Our study indicated that
the frequency of psychiatric consultation was high. This indicates the high
demand for mental health services at the ED. A thorough psychiatric assessment
can provide adequate psychiatric services to acute patients; thereby possibly
preventing suicide attempters from later actually dying by suicide.
PMID- 29945427
TI - The Reliability and Validity of the Korean Version of the Autism-Spectrum
Quotient.
AB - Objective: This study was conducted to investigate the reliability and validity
of the Korean version of Autism-Spectrum Quotient (AQ). Methods: 20 participants
with high-functioning autism (HFA) and 99 normal participants were recruited. All
participants were completed the AQ and Empathy Quotient (EQ), and parents of the
HFA group completed the parent-report AQ. For testing the reliability, we
examined Cronbach's alpha, performed item analysis, and compared self versus
parent report score of HFA participants. For testing the validity, we compared
the difference of the score of AQ among HFA and control group using independent t
tests, and performed correlation analysis between AQ and EQ. The receiver
operation characteristic curve analysis was performed to determine a cut-off.
Results: The Korean version of the AQ exhibited adequate internal consistency,
and in most items, the HFA group scored higher in comparison to the control
group. It was demonstrated that AQ has good discriminant validity through the
confirmation of the significant difference in the AQ score between two groups.
The concurrent validity was established through the significant correlation
between AQ and EQ in the HFA group. The best estimate cut-off score of AQ for
screening was 23. Conclusion: The Korean version of the AQ was determined as a
reliable and valid instrument to assess HFA in Korean population.
PMID- 29945428
TI - Electroconvulsive Seizure Alters the Expression and Daily Oscillation of
Circadian Genes in the Rat Frontal Cortex.
AB - Objective: Electroconvulsive therapy (ECT) is the most effective treatment for
mood disorders. Accumulating evidence has suggested the important role of
circadian genes in mood disorders. However, the effects of ECT on circadian genes
have not been systemically investigated. Methods: We examined the expression and
daily oscillation of major circadian genes in the rat frontal cortex after
electroconvulsive seizure (ECS). Results: Firstly, mRNA and protein level were
investigated at 24 hr after single ECS (E1X) and repeated ECS treatements for 10
days (E10X), which showed more remarkable changes after E10X than E1X. mRNA
expression of Roralpha, Bmal1, Clock, Per1, and Cry1 was decreased, while Rev
erbalpha expression was increased at 24 hr after E10X compared to sham. The
proteins showed similar pattern of changes. Next, the effects on oscillation and
rhythm properties (mesor, amplitude, and acrophase) were examined, which also
showed more prominent changes after E10X than E1X. After E10X, mesor of Roralpha,
Bmal1, and Cry1 was reduced, and that of Rev-erbalpha was increased. Five genes,
Rev-erbalpha, Bmal1, Per1, Per2, and Cry2, showed earlier acrophase after E10X.
Conclusion: The findings suggest that repeated ECS induces reduced expression and
phase advance of major circadian genes in the in vivo rat frontal cortex.
PMID- 29945429
TI - Decision Making Regarding Key Elements of Korean Disaster Psychiatric Assistance
Teams Using the Analytic Hierarchy Process.
AB - Objective: The purpose of this study was to determine the key components of
Korean disaster psychiatric assistant teams (K-DPATs), to set up new mental
health service providing system for the disaster victims. Methods: We conducted
an analytic hierarchy process (AHP) involving disaster mental health experts,
using a pairwise comparison questionnaire to compare the relative importance of
the key components of the Korean disaster mental health response system. In
total, 41 experts completed the first online survey; of these, 36 completed the
second survey. Ten experts participated in panel meetings and discussed the
results of the survey and AHP process. Results: It was agreed that K-DPATs should
be independent of the existing mental health system (70.1%), funding for K-DPATs
should be provided by the Ministry of Public Safety, and the system should be
managed by the Ministry of Health (65.8%). Experts shared the view that K-DPAT
leaders would be suitable key decision makers for all types of disaster, with the
exception of those involving infectious diseases. Conclusion: K-DPAT, a new model
for disaster mental health response systems could improve the insufficiency of
the current system, address problems such as fragmentation, and fulfill disaster
victims' unmet need for early professional intervention.
PMID- 29945430
TI - Validation of the Zero-Heat-Flux thermometer (SpotOn(r)) in major gynecological
surgery to monitor intraoperative core temperature: a comparative study with
esophageal core temperature.
AB - BACKGROUND: The Zero-Heat-Flux technology of the SpotOn(r) sensor to measure core
temperature has been validated in vascular and cardiac surgery. Our aim was to
assess its validity in gynecological surgery in terms of time of measurement,
thermic status (hypo-, normo-, or hyperthermia) and the use of different warming
devices. METHODS: Prospective study in patients scheduled for major gynecological
surgery using 3 warming systems (Snuggle Warm(r), Lithotomy Underbody Blanket(r)
and Warmtac Pad(r)). Intraoperative temperature was simultaneously monitored
using the SpotOn(r) sensor and a Drager(r) esophageal probe; measurements were
taken after induction (T0), between 0 and 60 min (T1), between 60 and 120 min
(T2) and after 120 min (T3). We calculated the level of correlation between pairs
of measurements both overall and in subgroups with an acceptable difference of
less than 0.5oC. We built Bland-Altman plots, and calculated the Pearson
correlation (PC) and intraclass correlation coefficient (ICC) to test our data.
RESULTS: We recruited 70 patients and included 66 for analysis, giving a total of
401 paired measurements. Overall, the PC and ICC for paired temperature readings
were 0.82 and 0.90, respectively. The lowest levels of correlation were observed
after intubation, when a convective blanket was placed under the patient, and in
hypothermic patients. The highest correlations were observed at T2, and in
normothermic patients. CONCLUSIONS: We found a high overall correlation between
the SpotOn(r) and the esophageal probe, with negligible differences and almost
perfect agreement. The warming system used, time of measurement, and thermic
status appear to influence the level of correlation, but these differences were
not clinically significant.
PMID- 29945431
TI - Investigating propofol-sufentanil interaction using clinical endpoints and
processed electroencephalography: a prospective randomized controlled trial.
AB - BACKGROUND: Propofol and sufentanil target controlled infusion technology is used
with increasing frequency. Drug interaction modelling, using clinical endpoints
and processed electroencephalography helps determine optimal drug concentrations
to assure adequate anesthesia. METHODS: 60 patients were randomized to receive a
constant concentration of sufentanil (0.25 ng/ml [Group S0.25], 0.5 ng/ml [Group
S0.5], 0 ng/ml [Group S0]. Propofol was administered in steps of 0.5 MUg/ml, up
to 4 MUg/ml. Processed EEG (Bispectral Index, Narcotrend Index) and auditory
evoked potentials (composite A-Line autoregressive Index; cAAI), were recorded
simultaneously. Sufentanil-propofol interaction was assessed by Probit - and
nonlinear regression analysis. RESULTS: Sufentanil had a dose-dependent
synergistic effect on the effect-site concentration of propofol (MUg/ml)
associated with a 50% probability (EC50) of loss of responsiveness to verbal
command (S0: 2.84 MUg/ml, R2 0.773; S0.25: 1.95 MUg/ml, R2 0.862; S0.5: 1.48
MUg/ml, R2 0.887) and noxious stimulation (S0: 3.46 MUg/ml, R2 0.626 MUg/ml;
S0.25: 2.17 MUg/ml, R2 0.853; S0.5: 1.69 MUg/ml, R2 0.897). Non-linear regression
analysis revealed a synergistic sufentanil effect on the propofol EC50 for BIS
(S0: 3.36 MUg/ml, R2 0.79; S0.25: 2.77 MUg/ml, R2 0.86 MUg/ml; S0.5: 2.6 MUg/ml,
R2 0.84), Narcotrend Index (S0: 3.57 MUg/ml, R2 0.66; S0.25: 2.91 MUg/ml, R2
0.70; S0.5: 2.02 MUg/ml, R2 0.51) and cAAI (S0: 3.42 MUg/ml, R2 0.59; S0.25: 3.00
MUg/ml, R2 0.63; S0.5: 3.14 MUg/ml, R2 0.59). CONCLUSIONS: Sufentanil has a
synergistic effect on the clinically observed hypnotic properties of propofol.
These findings apply also to the depth of hypnosis measured by the Bispectral
Index, Narcotrend Index and cAAI.
PMID- 29945432
TI - Volatile anesthetics versus propofol in the cardiac surgical setting of remote
ischemic preconditioning: a secondary analysis of a Cochrane Systematic Review.
AB - INTRODUCTION: So far, the concept of remote ischemic preconditioning (RIPC)
failed its translation from experimental to clinical studies. In addition to our
Cochrane Systematic Review, we systematically assessed the use of the intravenous
anesthetic propofol, as a potential confounding factor. EVIDENCE ACQUISITION: We
searched CENTRAL, MEDLINE, Embase and Web of Science. We included randomized
controlled trials comparing RIPC with no RIPC in adult patients scheduled for
coronary artery bypass graft surgery (with or without valve surgery) receiving
either exclusively propofol or exclusively volatile anesthetics. Two authors
independently assessed methodological quality and extracted data. We report odds
ratios (ORs) with 95% confidence intervals as our summary statistics are based on
random-effects models. EVIDENCE SYNTHESIS: We included 14 studies involving 4060
participants. We found no difference in treatment effect between the propofol and
volatile anesthetic groups when RIPC or no RIPC is applied on a composite
endpoint (all-cause mortality, non-fatal myocardial infarction and/or any new
stroke), all-cause mortality, non-fatal myocardial infarction, stroke, or length
of stay on ICU. On cardiac markers, RIPC did show a treatment effect on cardiac
troponin T measured as AUC 72 hours (SMD -0.80, CI -1.34, -0.25) in the propofol
group. However, these findings have to be interpreted with great caution, to date
only a very limited number of patients received volatile anesthetics in RIPC
trials (minimum N.=15, maximum N.=232). CONCLUSIONS: Present data do not permit a
final assessment regarding the role of volatile or intravenous anesthetics as a
possible confounding factor in RIPC trials.
PMID- 29945433
TI - Shivering prevention and treatment during cesarean delivery under neuraxial
anesthesia: a systematic review.
AB - INTRODUCTION: Perioperative shivering during cesarean sections (CSs) under
neuraxial anesthesia (NA) is clinically common but often under-treated. It may
prominently increase oxygen consumption, which can be catastrophic for
parturients with ischemic cardiovascular disease. Thus, the prevention and
treatment of shivering may be of great significance in parturients. The purpose
of this systematic review was to investigate the effectiveness of several drugs
on shivering prevention and treatment during CSs under NA. EVIDENCE ACQUISITION:
A literature search was carried out using PubMed, EMBASE and the Cochrane Library
to identify relevant studies. After literature screening and information
extraction, a systematic review was performed. EVIDENCE SYNTHESIS: Eighteen
randomized controlled trials met the inclusion criteria. Intrathecal
dexmedetomidine effectively reduced shivering, but effectiveness depended on the
dose administered. Intrathecal fentanyl, intrathecal sufentanil, intrathecal
meperidine, intravenous ketamine and intravenous tramadol were beneficial for
reducing shivering during CSs under NA. MgSO4 administered intrathecally resulted
in transient alleviation of shivering, and the effect did not persist. Two trials
investigated the antishivering effect of intravenous ondansetron. The medication
appeared to be effective in one trial, but ineffective in the other. CONCLUSIONS:
Appropriate use of dexmedetomidine, fentanyl, sufentanil, ketamine, meperidine,
tramadol and MgSO4 may effectively reduce the incidence and severity of shivering
during CSs under NA, while trials on the effect of intravenous ondansetron
reached inconclusive results.
PMID- 29945434
TI - Utilisation of echocardiography in intensive care units: results of an online
survey in Germany.
AB - BACKGROUND: In patients with haemodynamic instability echocardiography has been
recommended as the preferred modality to evaluate the underlying pathophysiology.
However, due to the fact that recent scientific data on the utilisation of
echocardiography in German intensive care units (ICU) are scarce, we sought to
investigate current practice. METHODS: A structured, web-based, anonymised survey
was performed from May until July 2015 among members of the German
Interdisciplinary Association of Critical Care and Emergency Medicine (DIVI)
consisting of 14 questions. Descriptive data analysis was performed. RESULTS: 104
intensivists participated in the survey. Two-thirds of participants (66%) used
echocardiography regularly for haemodynamic monitoring and stated that it changed
the therapy in 26-50% of the cases irrespective of the time performed after
ordering the examination. Transthoracic (TTE) were more frequently used than
transoesophageal (TEE) examinations. Twenty-six percent of the participants held
an echocardiography certificate with a formal examination, 27% completed a
structured training without an examination and almost half of the questioned ICU
personnel (47%) did not complete a comprehensive training. CONCLUSIONS: The
results of this survey demonstrate a widespread utilisation of echocardiography
as part of routine diagnostic on frequent number of operative ICUs. However,
there might be a lack of structured echocardiographic training especially for
anaesthesiologists.
PMID- 29945435
TI - Considerations in treating obese patients in office-based anesthesia.
AB - The rise in obesity prevalence worldwide has presented problems for practitioners
treating patients in the ambulatory setting. As more procedures are being
performed in office-based suites, anesthesiologists are being asked to provide
more anesthesia services for obese patients that may compromise safety.
Conventional wisdom associates a higher body-mass index (BMI) with the potential
for more adverse outcomes. When combined with the limited resources available in
office-based anesthesia (OBA) locations, this prompts anesthesiologists to
consider placing limits on BMI. However, not every OBA location is similar, thus
contributing to the difficulty in establishing consensus BMI limits. Here, we
review literature addressing obesity in ambulatory surgery and point out concerns
that anesthesiologists should consider when treating obese patients in an OBA
setting.
PMID- 29945436
TI - Can you stand the pressure? Insights from a cadaver study.
PMID- 29945437
TI - Caudal block in an extremely low-birthweight infant.
PMID- 29945438
TI - Does the transversus abdominis plan block play a role on length of stay? Results
of a retrospective observational study on 208 patients after laparoscopic
cholecystectomy.
PMID- 29945439
TI - Laryngeal mask and desflurane: safety first of all!
PMID- 29945440
TI - Multifunctional Additives Improve the Electrolyte Properties of Magnesium
Borohydride Toward Magnesium-Sulfur Batteries.
AB - Highly reductive magnesium borohydride [Mg(BH4)2] is compatible with metallic Mg,
making it a promising Mg-ion electrolyte for rechargeable Mg batteries. However,
pure Mg(BH4)2 in ether-based solutions displays very limited solubility (0.01 M),
low oxidative stability (<1.8 V vs Mg), and nucleophilic characteristic, all of
which preclude its practical utilization for any battery applications. Herein, we
present a multifunctional additive of tris(2 H-hexafluoroisopropyl)borate (THFPB)
for preparing Mg(BH4)2-based electrolytes. By virtue of the strong electron
acceptor ability of the THFPB molecule, a transparent and high-concentration
Mg(BH4)2/THFPB-diglyme (DGM) electrolyte (0.5 M, almost 50 times higher than that
of the pristine Mg(BH4)2-DGM electrolyte) is first obtained, which shows dramatic
performance improvements, including high ionic conductivity (3.72 mS cm-1 at 25
degrees C) and high Mg plating/stripping Coulombic efficiency (>99%). The newly
generated active cation and anion species revealed by Raman, NMR and MS spectra,
increase the electrochemical potential window from 1.8 V to 2.8 V vs Mg on
stainless steel electrode, rendering electrolytes the ability to examine high
voltage cathodes. More importantly, on account of the non-nucleophilicity of
active electrolyte species, we present the first example of magnesium-sulfur (Mg
S) batteries using Mg(BH4)2-based electrolytes, which exhibit a high discharge
capacity of 955.9 and 526.5 mA h g-1 at the initial and 30th charge/discharge
cycles, respectively. These achievements not only provide an efficient and
specific strategy to eliminate the major roadblocks facing Mg(BH4)2-based
electrolytes but also highlight the profound effect of functional additives on
the electrochemical performances of unsatisfied Mg-ion electrolytes.
PMID- 29945441
TI - Tunable Nonthermal Distribution of Hot Electrons in a Semiconductor Injected from
a Plasmonic Gold Nanostructure.
AB - For semiconductors photosensitized with organic dyes or quantum dots, transferred
electrons are usually considered thermalized at the conduction band edge. This
study suggests that the electrons injected from a plasmonic metal into a thin
semiconductor shell can be nonthermal with energy up to the plasmon frequency. In
other words, the electrons injected into the semiconductor are still hot
carriers. Photomodulated X-ray absorption measurements of the Ti L2,3 edge are
compared before and after excitation of the plasmon in Au@TiO2 core-shell
nanoparticles. Comparison with theoretical predictions of the X-ray absorption,
which include the heating and state-filling effects from injected hot carriers,
suggests that the electrons transferred from the plasmon remain nonthermal in the
~10 nm TiO2 shell, due in part to a slow trapping in defect states. By repeating
the measurements for spherical, rod-like, and star-like metal nanoparticles, the
magnitude of the nonthermal distribution, peak energy, and number of injected hot
electrons are confirmed to be tuned by the plasmon frequency and the sharp
corners of the plasmonic nanostructure. The results suggest that plasmonic
photosensitizers can not only extend the sunlight absorption spectral range of
semiconductor-based devices but could also result in increased open circuit
voltages and elevated thermodynamic driving forces for solar fuel generation in
photoelectrochemical cells.
PMID- 29945443
TI - Salt-Induced Assembly Transformation of DNA-AuNP Conjugates Based on RCA Origami:
From Linear Arrays to Nanorings.
AB - We developed a simple method to adjust the structural transformation of DNA-gold
nanoparticles assemblies from linear arrays to nanorings by increasing salt
concentrations. A DNA nanoladder constructing from RCA origami acted as templates
to assemble periodic AuNPs arrays by a terminal thiol located on staple
oligonucleotides. The linear AuNPs arrays could be transformed into nanorings
only by changing the concentration of NaCl aqueous solution during the assembly
process. It was proven that the electrostatic repulsion, being asymmetrically
diminished by the high concentration of NaCl, caused the formation of nanoring
architectures.
PMID- 29945442
TI - Electron-Beam Manipulation of Silicon Dopants in Graphene.
AB - The direct manipulation of individual atoms in materials using scanning probe
microscopy has been a seminal achievement of nanotechnology. Recent advances in
imaging resolution and sample stability have made scanning transmission electron
microscopy a promising alternative for single-atom manipulation of covalently
bound materials. Pioneering experiments using an atomically focused electron beam
have demonstrated the directed movement of silicon atoms over a handful of sites
within the graphene lattice. Here, we achieve a much greater degree of control,
allowing us to precisely move silicon impurities along an extended path,
circulating a single hexagon, or back and forth between the two graphene
sublattices. Even with manual operation, our manipulation rate is already
comparable to the state-of-the-art in any atomically precise technique. We
further explore the influence of electron energy on the manipulation rate,
supported by improved theoretical modeling taking into account the vibrations of
atoms near the impurities, and implement feedback to detect manipulation events
in real time. In addition to atomic-level engineering of its structure and
properties, graphene also provides an excellent platform for refining the
accuracy of quantitative models and for the development of automated
manipulation.
PMID- 29945444
TI - Inhibition of Heat-Induced Flocculation of Myosin-Based Emulsions through Steric
Repulsion by Conformational Adaptation-Enhanced Interfacial Protein with an
Alkaline pH-Shifting-Driven Method.
AB - Protein conformational rearrangement triggered by adsorption to the hydrophobic
interface of oil droplets has long been considered as a key factor in
emulsification. In this study, an alkaline pH-shifting-driven conformational
adaptation enhanced interfacial proteins was used to improve their stability
against heat-induced flocculation of myosin emulsions. We used the unfolded
myosin at pH 12 to emulsify soy oil and then readjusted the pH of the emulsion to
neutral. The corresponding myosin emulsion (0.5% w/v protein, 10% v/v soy oil,
and 0.6 M NaCl) almost not flocculated when heated at 75 degrees C for 30 min.
Moreover, after thermal treatment, the particle size of the emulsion was not
significantly increased ( P > 0.05) and the emulsion did not exhibit a creaming
phenomenon after a week. Based on the circular dichroism and Fourier transform
infrared analysis, we speculated the superiority of the emulsion is closely
related to the alkaline pH-shifting-driven conformational adaptation enhanced
interfacial protein. Additionally, the resulting steric stabilization in
overcoming the attractive hydrophobic forces between denatured protein molecules
coated droplets might be the main factor for the inhibition of heat-induced
flocculation of the emulsion. Our research may have important implications for
the formulation of protein-stabilized oil-in-water emulsions.
PMID- 29945445
TI - In Situ Electrochemical Tip-Enhanced Raman Spectroscopy with a Chemically
Modified Tip.
AB - Chemically modified tips in scanning tunneling microscopy (STM) and atomic force
microscopy (AFM) have been used to improve the imaging resolution or provide
richer chemical information, mostly in ultrahigh vacuum (UHV) environments. Tip
enhanced Raman spectroscopy (TERS) is a nanoscale spectroscopic technique that
already provides chemical information and can provide subnanometer spatial
resolution. Chemical modification of TERS tips has mainly been focused on
increasing their lifetimes for ambient and in situ experiments. Under UHV
conditions, chemical functionalization has recently been carried out to increase
the amount of chemical information provided by TERS. However, this strategy has
not yet been extended to in situ electrochemical (EC)-TERS studies. The
independent control of the tip and sample potentials offered by EC-STM allows us
to prove the in situ functionalization of a tip in EC-STM-TERS. Additionally, the
Raman response of chemically modified TERS tips can be switched on and off at
will, which makes EC-STM-TERS an ideal platform for the development of in situ
chemical probes on the nanoscale.
PMID- 29945446
TI - Oleuropein Curtails Pulmonary Inflammation and Tissue Destruction in Models of
Experimental Asthma and Emphysema.
AB - Airway inflammation has been implicated in evoking progressive pulmonary
disorders including chronic obstructive pulmonary disease (COPD) and asthma as a
result of exposure to inhaled irritants, characterized by airway fibrosis, mucus
hypersecretion, and loss of alveolar integrity. The current study examined
whether oleuropein, a phenylethanoid found in olive leaves, inhibited pulmonary
inflammation in experimental models of interleukin (IL)-4-exposed bronchial BEAS
2B epithelial cells and ovalbumin (OVA)- or cigarette smoke (CS)-exposed BALB/c
mice. Nontoxic oleuropein at 1-20 MUM diminished eotaxin-1-mediated induction of
alpha-smooth muscle actin and mucin 5AC in epithelial cells stimulated by IL-4 at
the transcriptional levels. Oral supplementation of 10-20 mg/kg oleuropein
reduced the airway influx of eosinophils and lymphocytes as well as IL-4
secretion in lung promoted by OVA inhalation or CS. In addition, oleuropein
suppressed infiltration of macrophages and neutrophils through blocking OVA
inhalation- and CS-promoted induction of ICAM-1, F4/80, CD68, and CD11b in
airways. OVA-exposed pulmonary fibrosis was detected, while alveolar emphysema
was evident in CS-exposed mouse lungs. In alveolar epithelial A549 cells exposed
to CS extracts, oleuropein attenuated apoptotic cell loss. Collectively,
oleuropein inhibited pulmonary inflammation leading to asthmatic fibrosis and
alveolar emphysema driven by influx of inflammatory cells in airways exposed OVA
or CS. Therefore, oleuropein may be a promising anti-inflammatory agent for
treating asthma and COPD.
PMID- 29945447
TI - Structural and Optical Investigations of Quasi-Single Crystal Eu3+-Doped BaWO4
Thin Films.
AB - Scheelite-structure tungstates with unique structural features and excellent
luminescence possess promising applications, such as light-emitting diodes
(LEDs), scintillators, and displays. The controllable growth of high quality and
uniform composition thin films mounted on cheap substrates is a key factor to
realize the above commercial applications, however, which is also a big challenge
due to the difficult stress release stemming from intrinsic lattice mismatches.
Here, we employed the simple and composition-controlled polymer-assisted
deposition (PAD) method to successfully obtain a series of high quality and well
proportioned BaWO4:Eu3+ (BWOE) thin films with red emission. Screening out the
unbound freedom metal ions by poly(ether imide) (PEI) and ethylene diamine
tetraacetic acid (EDTA), the firmly bound metal ions (Ba2+, W6+ and Eu3+) in
polymer solution were applied to accurately control the chemical composition and
effectively governed the release of stress during the growth process of BWOE thin
films. Furthermore, XRD, SEM and EDS mapping detections evidently authenticated
the quasi-single crystallinity, uniform morphology and well-distributed
composition of as-grown thin films. Additionally, excited by 250 nm light, these
thin films could efficiently produce the red emission, peaked at around 612 nm
originated from the 5 D0 -> 7 F2 transition of Eu3+. Moreover, the optimal doping
concentration of thin films was confirmed to be 9% and corresponding Commission
International de l'Eclairage (CIE) chromaticity coordinate was (0.618, 0.365),
which evidently implied the excellent color rending index. Therefore, this work
highlights the rather superior PAD method to prepare uniform and high-quality
BWOE thin films, which can be expanded toward the other photoelectric devices
including white lighted-emitting diodes, scintillators, displays, and
photoelectric detectors.
PMID- 29945448
TI - Apigenin Suppresses the IL-1beta-Induced Expression of the Urokinase-Type
Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-kappaB
Signaling in Human Bladder Cancer T24 Cells.
AB - The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein
localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a
crucial role in cell invasion, and the metastasis of several cancers, including
bladder cancer, and its expression are significantly negatively correlated with
patient survival rates. Apigenin, a naturally produced phytochemical compound
found in fruits, vegetables, and plant leaves, has been shown to mediate a
variety of cancer-metastasis-related molecules in various cancers. The effect of
apigenin on uPAR expression is still unknown. In this study, we examined the
effects of apigenin on IL-1beta-induced uPAR expression and investigated its
potential mechanisms. We discovered in this study that IL-1beta could remarkably
induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL
1beta could induce uPAR expression concentration-dependently. Interestingly, NF
kappaB and AP-1 transcription factors were critically required for IL-1beta
induced high uPAR expression. Apigenin suppressed the transcriptional activity of
both AP-1 and NF-kappaB by inhibiting ERK1/2 and JNK signaling pathways. These
results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR
expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-kappaB signaling
pathways in human T24 cells. Our present study generated novel and valuable
biological insight into anti-invasion through treatment with a small native
compound.
PMID- 29945449
TI - Activation Energies and Diffusion Coefficients of Polarons and Bipolarons in
Organic Conductors.
AB - Intrachain diffusion of charge carriers in organic conductors is analyzed. Using
a tight-binding model Hamiltonian that includes strong electron-phonon coupling
combined with a Langevin equation, we simulate both polaron and bipolaron
dynamics under quantum-corrected thermal effects. Nonadiabatic molecular time
evolution is used to determine how these quasiparticles diffuse through a
nondegenerate conjugated polymer. By means of a phenomenological approach, we
evaluate the diffusion coefficient and activation energies for the motion of both
polarons and bipolarons. The analysis of activation energies, in agreement with
available experimental data, suggests that the presence of bipolarons may inhibit
the efficiency of organic-based devices. The results presented here point to the
importance of taking a closer look at the effects of bipolaron dynamics in
organic devices.
PMID- 29945453
TI - Infection Status Can Affect White Blood Cell Parameters.
PMID- 29945450
TI - Transformative Opportunities for Single-Cell Proteomics.
AB - Many pressing medical challenges, such as diagnosing disease, enhancing directed
stem-cell differentiation, and classifying cancers, have long been hindered by
limitations in our ability to quantify proteins in single cells. Mass
spectrometry (MS) is poised to transcend these limitations by developing powerful
methods to routinely quantify thousands of proteins and proteoforms across many
thousands of single cells. We outline specific technological developments and
ideas that can increase the sensitivity and throughput of single-cell MS by
orders of magnitude and usher in this new age. These advances will transform
medicine and ultimately contribute to understanding biological systems on an
entirely new level.
PMID- 29945454
TI - Functionality and Risk of Falls in Elders Followed in a Day Care Center in
Brazil.
AB - Adult day centers provide comprehensive care for older adults and may enhance
autonomy, well-being, and socialization. This quasi-experimental study evaluated
the impact of such multidisciplinary day care on functionality, fear of falling,
and risk of falls in community elders. Fifty-two seniors who attended day
services were followed for 1 year. During the year, the adults maintained
functionality for activities of daily living, presented improvement in
instrumental activities of daily living, and no longer presented high risk for
falls. No association was found between the risk of falling and fear of falling,
however. Results are discussed in terms of the positive outcomes of attending day
services.
PMID- 29945451
TI - Estimating the Distribution of Protein Post-Translational Modification States by
Mass Spectrometry.
AB - Post-translational modifications (PTMs) of proteins play a central role in
cellular information encoding, but the complexity of PTM state has been
challenging to unravel. A single molecule can exhibit a "modform" or
combinatorial pattern of co-occurring PTMs across multiple sites, and a molecular
population can exhibit a distribution of amounts of different modforms. How can
this "modform distribution" be estimated by mass spectrometry (MS)? Bottom-up MS,
based on cleavage into peptides, destroys correlations between PTMs on different
peptides, but it is conceivable that multiple proteases with appropriate patterns
of cleavage could reconstruct the modform distribution. We introduce a
mathematical language for describing MS measurements and show, on the contrary,
that no matter how many distinct proteases are available, the shortfall in
information required for reconstruction worsens exponentially with increasing
numbers of sites. Whereas top-down MS on intact proteins can do better, current
technology cannot prevent the exponential worsening. However, our analysis also
shows that all forms of MS yield linear equations for modform amounts. This
permits different MS protocols to be integrated and the modform distribution to
be constrained within a high-dimensional "modform region", which may offer a
feasible proxy for analyzing information encoding.
PMID- 29945455
TI - Validity and Reliability of the Dying Care Process and Outcome Scales Before and
After Death From the Bereaved Family Members' Perspective.
AB - OBJECTIVE: There are no instruments evaluating the processes and outcomes of
dying care right before and after death. Therefore, we developed and examined the
validity and reliability of 2 scales for evaluating dying care processes and
outcomes before and after death. METHODS: A cross-sectional, anonymous
questionnaire was administered to bereaved family members of patients with cancer
who had died in 5 facilities. We evaluated the Dying Care Process Scale for
Bereaved Family Members (DPS-B) and the Dying Care Outcome Scale for Bereaved
Family Members (DOS-B) with 345 bereaved family members. RESULTS: A factor
analysis revealed that DPS-B and DOS-B each consisted of 4 subscales. For the DPS
B, they were "symptom management," "respect for the patient's dignity before and
after death," "explanation to the family," and "family care." For the DOS-B, they
were "peaceful dying process for the patient," "being respected as a person
before and after death," "good relationship between the patient and family," and
"peaceful dying process for the family." Both DPS-B and DOS-B had sufficient
convergent and discriminative validity, sufficient internal consistency (DPS-B:
alpha = 0.91 and subscales' alphas = 0.78-0.91; DOS-B: alpha = 0.91 and
subscales' alphas = 0.78-0.94), and sufficient test-retest reliability (DPS-B:
intraclass correlation coefficient [ICC] of total score = 0.79 and subscales =
0.55-0.79; DOS-B: ICC of total score = 0.88 and subscales = 0.70-0.88).
SIGNIFICANCE OF RESULTS: Both DPS-B and DOS-B are valid and reliable scales for
evaluating the dying care processes and outcomes before and after death from the
bereaved family members' perspectives.
PMID- 29945456
TI - Long-term survival after R0 resection of thymoma.
AB - Background The aim of this study was to evaluate the results of R0 resection of
thymoma to identify prognostic factors for long-term outcomes. Methods Data of 62
patients (28 male, 34 female) with a mean age of 47.26 +/- 14.42 years, who
underwent R0 resection for thymoma and were followed-up between February 2004 and
March 2016, were analyzed retrospectively. Results Eight patients had a video
assisted thoracoscopic thymectomy and 54 had a transsternal extended thymectomy.
During a mean follow-up of 128.67 +/- 7.95 months, regional recurrence of thymoma
was observed in 9 (14.5%) patients. Overall 5- and 10-year survival rates were
85.36% and 78.20%, respectively. The 5- and 10-year survival rates in patients
aged < 50 years were significantly better than in those aged >= 50 years (92% and
72% vs. 88% and 39%, p < 0.0001). The 10-year overall survival of patients in
Masaoka stage I and II was better than those in stage III (88.9%, 78.4%, 69.8%,
respectively, log-rank p < 0.001). The 10-year survival of patients with World
Health Organization histological type A, AB, and B1 thymomas was better than
those with type B2 and B3 (log-rank test p < 0.001). In multivariate analysis,
age < 50 years ( p = 0.001), Masaoka stage ( p = 0.006), histological type ( p =
0.001), and recurrence ( p = 0.04) were independent prognostic factors for
survival. Conclusion Our study indicates that age < 50 years, Masaoka stage,
histological type, and recurrence are the determinants of survival in surgically
resected cases of thymoma.
PMID- 29945457
TI - The Association of Biomarkers of Inflammation and Extracellular Matrix
Degradation With the Risk of Abdominal Aortic Aneurysm: The ARIC Study.
AB - Animal and human laboratory studies suggest that the pathogenesis of abdominal
aortic aneurysms (AAAs) involves inflammation and degradation and remodeling of
the extracellular matrix. This study prospectively assessed the association
between biomarkers for these mechanisms and the presence of AAA during 24 years
of follow-up in the Atherosclerosis Risk in Communities (ARIC) study. The ARIC
prospectively identified clinically diagnosed AAAs in 15 792 men and women from
baseline in 1987 to 1989 to 2011 using hospital discharge codes and death
records. Additional asymptomatic AAAs were detected by an abdominal ultrasound
scan in 2011 to 2013. Matrix metalloproteinase (MMP)-3, MMP-9, interleukin 6 (IL
6), N-terminal propeptide of Type III procollagen (PIIINP), and osteopontin were
measured in blood samples collected between 1987 and 1992 in participants with
AAA (544 clinically diagnosed AAAs and 72 ultrasound-detected AAAs) and a random
sample of 723 participants selected from baseline and matched with AAAs by age,
race and sex. Higher concentrations of MMP-9 and IL-6 were associated with future
risk of clinically diagnosed AAA (hazard ratios [95% confidence intervals]: 1.55
[1.22-1.97] and 1.87 [1.48-2.35], respectively, comparing highest versus lowest
tertiles) after multivariable adjustment ( P for trend < .001). Matrix
metalloproteinase-9 was also associated with ultrasound-detected AAA. In
conclusion, blood concentrations of MMP-9 and IL-6 measured in middle age
predicted the risk of AAA during 24 years of follow-up.
PMID- 29945458
TI - Feasibility and psychometric properties of the Finnish version of the measure of
processes of care for adults.
AB - OBJECTIVE:: To assess the psychometric properties and feasibility of the Finnish
translation of the measure of processes of care for adults (MPOC-A) when used in
an inpatient rehabilitation setting. DESIGN:: A feasibility study. SETTINGS::
Inpatient rehabilitation settings. SUBJECTS:: A total of 858 people with severe
neurological disabilities, musculoskeletal problems, and mental disorders were
recruited to the study. METHODS:: The MPOC-A questionnaire is a self-administered
questionnaire consisting of 34 items in five-factorial domains. The construct
validity of the translated questionnaire was evaluated using confirmatory factor
analysis. To compare the fit of the model to the fit of the independent null
model Comparative Fit Index was used. Internal consistency for the total scale
and subscales was calculated using Cronbach's alpha reliability coefficient.
RESULTS:: A total of 554 people, mean age 52 years (SD = 9), participated in the
study. Most of the responders had musculoskeletal problems ( n = 328, 57%). The
respondents rated the client-centeredness in rehabilitation service as moderate (
m = 5.40, SD = 0.81). The five-factor and the one-factor model fitted the data
well according to all three indices. Internal consistency showed high reliability
between the one-factor and five-factor models for all except one domain (0.49
0.93). The mean for Person Infit for the people with neurological disabilities
was higher than for the other two groups ( m = 1.77, SD = 1.32) indicating less
predictable response patterns in this group. CONCLUSION:: The results confirm the
appropriate psychometric properties of the Finnish version of the MPOC-A,
especially for people with musculoskeletal problems and those with mental health
disorders.
PMID- 29945459
TI - Chinese enclave protections among married Chinese American women: exploratory
secondary analysis of colon cancer survival.
AB - OBJECTIVE: Like the barrio advantage theory related to Mexican Americans, a
theory about the protective effects of Chinese American enclaves is developing.
Such protections were examined among socioeconomically vulnerable people with
colon cancer. DESIGN: A colon cancer cohort established in California between
1995 and 2000, and followed until the enactment of the Affordable Care Act was
utilized in this study. Secondary analysis was conducted on the 5-year survival
among 127 Chinese Americans and 4524 other Americans (3810 non-Hispanic white and
714 Hispanic people). A third of the original cohort was selected from high
poverty neighborhoods. Chinese American enclaves were neighborhoods where
typically 25% or more of the residents were Chinese Americans. Effects were
tested with Cox regressions and group differences described with age and stage
standardized survival rate ratios (RR). RESULTS: Though they were less adequately
insured, Chinese American women residing in Chinese American enclaves (63%) were
more likely to survive than were other Americans (50%, RR = 1.26). The protective
effect of being married was also larger for Chinese Americans (RR = 1.31) than
for others (RR = 1.17). Chinese American women (61%) were more likely than men
(46%) to live in such enclaves and a large enclave survival advantage was
observed among Chinese American women only (RR = 1.59). CONCLUSIONS: There is
consistent evidence of the relatively protected status of Chinese American women,
particularly those who were married and resided in Chinese American enclaves.
Mechanisms that explain their apparent advantages are not yet well understood,
though relatively large, kin-based social networks seem instrumental. Research on
the influence of social networks as well as the possible effects of acculturation
is needed. This study also exposed structural inequities related to the
institutions of marriage, health care and communities that disadvantage others.
Policy makers ought to be aware of them as future reforms of American health care
are considered.
PMID- 29945460
TI - Inline Spectroscopy: From Concept to Function.
AB - The field of applied spectroscopy is strongly dominated by publications
presenting proof-of-concepts, lab set-ups, and demonstrations. In contrast, the
corresponding number of commercial successes of inline spectroscopy is
surprisingly lower. This article discusses inline spectroscopy from an
instrumentation perspective. It is the authors' firm belief that the success of
inline spectroscopy lies in the understanding of how the design and
implementation of the optical instrumentation affects the data quality, and how
this in turn will limit or enhance the performance of the prediction model. This
article emphasizes the need for a strong, multidisciplinary design team, whose
design process is rooted in first principles, to bridge the technology "valley of
death" and convert research in applied spectroscopy into commercially successful
solutions.
PMID- 29945461
TI - Effects of tris(1-chloro-2-propyl)phosphate and tris(2-chloroethyl)phosphate on
cell viability and morphological changes in peripheral blood mononuclear cells
(in vitro study).
AB - Organophosphorus flame retardants (OPFRs) are a group of chemicals widely used in
various everyday use products. Tris(2-chloroethyl)phosphate (TCEP) and tris(1
chloro-2-propyl)phosphate (TCPP) are one of the commonly used chemicals belonging
to this group. Due to the need of limitation of the use of polybrominated
diphenyl ethers (PBDEs) as retardants, the share of the compounds tested in our
experiments in chemicals production systematically increases. There is limited
information about the influence of halogenated OPFRs on living cells, especially
on the immune system cells. That is why the aim of this study was to assess the
impact of TCEP and TCPP on viability and morphological alterations of human
peripheral blood mononuclear cells (PBMCs). The cells were incubated with
selected flame retardants in the concentrations ranging from 0.001 to 1 mM for 24
h. It was found that TCEP at 1 mM and TCPP at 0.5 mM decreased viability of
PBMCs, while only TCPP induced morphological alterations in the incubated cells.
The results of our experiments suggest that TCPP is more cytotoxic than TCEP,
which can be explained by the presence of methyl groups in the molecule of this
compound. Similar to other studies, our data also suggest that OPFRs are suitable
replacements for PBDEs.
PMID- 29945462
TI - Aryl-tetralin-type lignan isolated from Sanguisorba officinalis.
AB - Three aryl-tetralin-type lignans, including 2 previously undescribed compounds,
were isolated from the root of Sanguisorba officinalis. The structures of the new
compounds were elucidated by 1D- and 2D-NMR spectroscopic analyses and mass
spectrometry. Experimental and calculated ECD were used to determine the absolute
configurations. The isolated compounds were evaluated for cytotoxicity against
two cell lines (MV4-11 and MDA-MB-231) and compound 1 exhibited moderate growth
inhibition against MDA-MB-231 cell line with IC50 value of 15.76 MUM.
PMID- 29945463
TI - Calcium: A Crucial Potentiator for Efficient Enzyme Digestion of the Human
Pancreas.
AB - BACKGROUND: Effective digestive enzymes are crucial for successful islet
isolation. Supplemental proteases are essential because they synergize with
collagenase for effective pancreatic digestion. The activity of these enzymes is
critically dependent on the presence of Ca2+ ions at a concentration of 5-10 mM.
The present study aimed to determine the Ca2+ concentration during human islet
isolation and to ascertain whether the addition of supplementary Ca2+ is required
to maintain an optimal Ca2+ concentration during the various phases of the islet
isolation process. METHODS: Human islets were isolated according to standard
methods and isolation parameters. Islet quality control and the number of
isolations fulfilling standard transplantation criteria were evaluated. Ca2+ was
determined by using standard clinical chemistry routines. Islet isolation was
performed with or without addition of supplementary Ca2+ to reach a Ca2+ of 5 mM.
RESULTS: Ca2+ concentration was markedly reduced in bicarbonate-based buffers,
especially if additional bicarbonate was used to adjust the pH as recommended by
the Clinical Islet Transplantation Consortium. A major reduction in Ca2+
concentration was also observed during pancreatic enzyme perfusion, digestion,
and harvest. Additional Ca2+ supplementation of media used for dissolving the
enzymes and during digestion, perfusion, and harvest was necessary in order to
obtain the concentration recommended for optimal enzyme activity and efficient
liberation of a large number of islets from the human pancreas. CONCLUSIONS: Ca2+
is to a large extent consumed during clinical islet isolation, and in the absence
of supplementation, the concentration fell below that recommended for optimal
enzyme activity. Ca2+ supplementation of the media used during human pancreas
digestion is necessary to maintain the concentration recommended for optimal
enzyme activity. Addition of Ca2+ to the enzyme blend has been implemented in the
standard isolation protocols in the Nordic Network for Clinical Islet
Transplantation.
PMID- 29945465
TI - Depressive symptoms prospectively predict cardiovascular disease among older
adults: Findings from the Maine-Syracuse Longitudinal Study.
AB - A recent meta-analysis identified a prospective association between depression
and cardiovascular disease; however, there was no association for studies with
long-term follow-up periods. The literature has primarily focused on baseline
depression status or symptoms, which may not capture the chronic nature of
depression. This study examined the prospective relationship between depressive
symptoms and cardiovascular disease up to 15 years later in 274 cardiovascular
disease-free older adults. Depressive and anxiety symptoms, mean arterial
pressure, and cardiovascular disease status were assessed. Baseline and chronic
depressive symptoms predicted increased risk of cardiovascular disease,
underscoring the importance of assessing and treating depression in older adults.
PMID- 29945464
TI - Psychological, clinical, and therapeutic predictors of the outcome of
detoxification in a large clinical population of medication-overuse headache: A
six-month follow-up of the COMOESTAS Project.
AB - Aim To identify factors that may be predictors of the outcome of a detoxification
treatment in medication-overuse headache. Methods Consecutive patients entering a
detoxification program in six centres in Europe and Latin America were evaluated
and followed up for 6 months. We evaluated anxious and depressive symptomatology
(though patients with severe psychiatric comorbidity were excluded), quality of
life, headache-related disability, headache characteristics, and prophylaxis upon
discharge. Results Of the 492 patients who completed the six-month follow up, 407
ceased overuse following the detoxification (non overusers), another 23 ceased
overuse following detoxification but relapsed during the follow-up. In the 407
non-overusers, headache acquired an episodic pattern in 287 subjects
(responders). At the multivariate analyses, lower depression scores (odds ratio =
0.891; p = 0.001) predicted ceasing overuse. The primary headache diagnosis -
migraine with respect to tension-type headache (odds ratio = 0.224; p = 0.001) or
migraine plus tension-type headache (odds ratio = 0.467; p = 0.002) - and the
preventive treatment with flunarizine (compared to no such treatment) (odds ratio
= 0.891; p = 0.001) predicted being a responder. A longer duration of chronic
headache (odds ratio = 1.053; p = 0.032) predicted relapse into overuse. Quality
of life and disability were not associated with any of the outcomes. Conclusions
Though exploratory in nature, these findings point to specific factors that are
associated with a positive outcome of medication-overuse headache management,
while identifying others that may be associated with a negative outcome.
Evaluation of the presence/absence of these factors may help to optimize the
management of this challenging groups of chronic headache sufferers.
PMID- 29945466
TI - Platforms for Investigating LncRNA Functions.
AB - Prior to the sequencing of the human genome, it was presumed that most of the DNA
coded for proteins. However, with the advent of next-generation sequencing, it
has now been recognized that most complex eukaryotic genomes are in fact
transcribed into noncoding RNAs (ncRNAs), including a family of transcripts
referred to as long noncoding RNAs (lncRNAs). LncRNAs have been implicated in
many biological processes ranging from housekeeping functions such as
transcription to more specialized functions such as dosage compensation or
genomic imprinting, among others. Interestingly, lncRNAs are not limited to a
defined set of functions but can regulate varied activities such as messenger RNA
degradation, translation, and protein kinetics or function as RNA decoys or
scaffolds. Although still in its infancy, research into the biology of lncRNAs
has demonstrated the importance of lncRNAs in development and disease. However,
the specific mechanisms through which these lncRNAs act remain poorly defined.
Focused research into a small number of these lncRNAs has provided important
clues into the heterogeneous nature of this family of ncRNAs. Due to the complex
diversity of lncRNA function, in this review, we provide an update on the
platforms available for investigators to aid in the identification of lncRNA
function.
PMID- 29945467
TI - Personalized Telemedicine for Depression in Parkinson's Disease: A Pilot Trial.
AB - High rates of depression are observed in Parkinson's disease, and limited access
to care complicates management. The purpose of this pilot project was to evaluate
the feasibility and impact of a personalized cognitive-behavioral telemedicine
program for depression in Parkinson's disease (dPD). Thirty-four individuals with
dPD and their carepartners participated in this pilot study. A 10-module self
help workbook, tailored to the unique needs of the dPD population, was created to
be used as either a stand-alone intervention, with minimal therapist support, or
a supplement to formal telephone-administered cognitive-behavioral therapy
sessions. Improvements in depression, anxiety, quality of life, sleep, negative
thoughts, and caregiver burden were observed over the course of the 4-month
study, independent of treatment modality (guided self-help vs formal telephone
based psychotherapy). Future research will utilize randomized controlled designs
and continue to focus on delivery models that can improve access to this and
other evidence-based mental health interventions for dPD.
PMID- 29945468
TI - Corrigendum.
PMID- 29945469
TI - High dose psilocybin is associated with positive subjective effects in healthy
volunteers.
AB - AIM: The aim of the current study was to investigate the relationship between
escalating higher doses of psilocybin and the potential psilocybin occasioned
positive subjective effects. METHODS: Healthy participants ( n=12) were given
three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or
(18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a
supervised setting. Blood and urine samples, vital signs, and electrocardiograms
were obtained. Subjective effects were assessed using the Mystical Experience
Questionnaire and Persisting Effects Questionnaire. RESULTS: There was a
significant linear dose-related response in Mystical Experience Questionnaire
total score and the transcendence of time and space subscale, but not in the rate
of a complete mystical experience. There was also a significant difference
between dose 3 compared to dose 1 on the transcendence of time and space
subscale, while no dose-related differences were found for Mystical Experience
Questionnaire total scores or rate of a mystical experience. Persisting Effects
Questionnaire positive composite scores 30 days after completion of the last dose
were significantly higher than negative composite scores. Persisting Effects
Questionnaire results revealed a moderate increase in sense of well-being or life
satisfaction on average that was associated with the maximum Mystical Experience
Questionnaire total score. Pharmacokinetic measures were associated with dose but
not with Mystical Experience Questionnaire total scores or rate of a mystical
experience. CONCLUSIONS: High doses of psilocybin elicited subjective effects at
least as strong as the lower doses and resulted in positive persisting subjective
effects 30 days after, indicating that a complete mystical experience was not a
prerequisite for positive outcomes.
PMID- 29945470
TI - Mediating Mechanisms in a Physical Activity Intervention: A Test of Habit
Formation.
AB - BACKGROUND: A recent randomized controlled trial found that an intervention
focused on developing an exercise habit increased weekly minutes of moderate to
vigorous physical activity (MVPA) over 8 wk compared to a control group. The
purpose of the current study was to test if changes in habit, as well as other
behavioral strategy constructs from the Multi-Process Action Control Test,
mediated between group condition and MVPA (self-report and accelerometry).
METHODS: Inactive new gym members (N = 94) were randomized into control or
experimental (habit-building) groups. RESULTS: No construct entirely explained
mediation condition (experimental and control) and changes in MVPA measured by
accelerometry. Self-report MVPA found affective judgments, behavioral regulation,
and preparatory habit to be mediated between group (experimental/control
conditions) and changes in behavior (beta = 0.36, 95% confidence interval [.05
.78]). CONCLUSIONS: Self-reported and objectively measured behavior models
demonstrated complete and partial mediation, respectively. New gym members could
benefit from successful behavioral enactment by developing constructs to support
habit formation.
PMID- 29945471
TI - Fate of the tributaries of sapheno femoral junction following endovenous thermal
ablation of incompetent axial vein - A review article.
AB - Sapheno femoral junctional tributaries are usually left untreated at the time of
endovenous ablation of axial vein. The long-term clinical significance of these
untreated tributaries remains elusive and there is very little research done into
this area. This article reviews the fate of untreated tributaries at sapheno
femoral junction following ablation of incompetent axial vein. A literature
search and analysis of evidence reveal that the junctional tributaries are one of
the commonest (ranges between 8% and 31%) cause for recurrence following
endovenous ablation of the axial veins. Follow up of this subset of patients
after their axial vein treatment should be considered to identify neoreflux in
side branches at sapheno femoral junction and plan treatment.
PMID- 29945472
TI - Midterm outcome of fourth-generation ceramic-on-ceramic bearing surfaces in
revision total hip arthroplasty.
AB - PURPOSE: The purpose of this study is to evaluate the clinical and radiologic
outcomes after revision total hip arthroplasty (THA) using fourth-generation
ceramic-on-ceramic (CoC) bearing surfaces. METHODS: A total of 52 revision THAs
(28 men and 19 women) using the fourth-generation CoC bearing surfaces were
retrospectively evaluated. Both acetabular cup and femoral stem were revised in
all cases. The mean follow-up period was 7.3 years (range, 4.0-9.9 years). The
clinical results with Harris hip score (HHS), Western Ontario McMaster
Osteoarthritis Index (WOMAC), and radiologic outcomes were evaluated. RESULTS: At
the final follow-up examination, the average HHS was 90.4 (range, 67-100). The
average WOMAC pain and physical function score were 2.8 (range, 0-12) and 16.4
(range, 0-42), respectively. Complications were observed in 10 hips (19.2%).
However, there were no bearing surface-related complications, and no cases of
dislocation and squeaking. Retroacetabular pelvic osteolysis without cup
loosening was observed in one hip at the final follow-up. However, no hip showed
radiographic signs of cup loosening, vertical or horizontal acetabular cup
migrations, and changes of inclinations during the follow-up period. CONCLUSION:
Our data showed that clinical and radiologic outcomes after revision THA using
fourth-generation CoC bearing were favorable. Hence, revision THA with the use of
CoC bearing surfaces can be preferentially considered. Further studies with long
term follow-up data are warranted.
PMID- 29945473
TI - The Effect of Incomplete Death Certificates on Estimates of Unintentional Opioid
Related Overdose Deaths in the United States, 1999-2015.
AB - OBJECTIVES: A complete and accurate count of the number of opioid-related
overdose deaths is essential to properly allocate resources. We determined the
rate of unintentional overdose deaths (non-opioid-related, opioid-related, or
unspecified) in the United States and by state from 1999 to 2015 and the possible
effects of underreporting on national estimates of opioid abuse. METHODS: We
abstracted unintentional drug overdose deaths ( International Classification of
Diseases, 10th Revision, codes X40-X44) with contributory drug-specific T codes
(T36.0-T50.9) from the Mortality Multiple Cause Micro-Data Files. We assumed that
the proportion of unspecified overdose deaths that might be attributed to opioids
would be the same as the proportion of opioid-related overdose deaths among all
overdose deaths and calculated the number of deaths that could be reallocated as
opioid-related for each state and year. We then added these reallocated deaths to
the reported deaths to determine their potential effect on total opioid-related
deaths. RESULTS: From 1999 to 2015, a total of 438 607 people died from
unintentional drug overdoses. Opioid-related overdose deaths rose 401% (from 5868
to 29 383), non-opioid-related overdose deaths rose 150% (from 3005 to 7505), and
unspecified overdose deaths rose 220% (from 2255 to 29 383). In 5 states
(Alabama, Indiana, Louisiana, Mississippi, and Pennsylvania), more than 35% of
unintentional overdose deaths were coded as unspecified. Our reallocation
resulted in classifying more than 70 000 unspecified overdose deaths as potential
additional opioid-related overdose deaths. CONCLUSIONS: States may be greatly
underestimating the effect of opioid-related overdose deaths because of
incomplete cause-of-death reporting, indicating that the current opioid overdose
epidemic may be worse than it appears.
PMID- 29945475
TI - Management and outcomes of 27 pregnancies in women with myeloproliferative
neoplasms.
AB - INTRODUCTION: Philadelphia-negative myeloproliferative neoplasms (MPNs) greatly
increase the risk of maternal and fetal complications during pregnancy.
Currently, international agreements regarding the management of these women are
lacking. PATIENTS AND METHODS: Our study aimed to assess the current management
and outcomes of MPN pregnancies in a French cohort. We retrospectively analyzed
27 pregnancies in women with MPNs that were associated with a specific mutation.
Nineteen pregnancies in nine women with essential thrombocythemia and eight
pregnancies in five women with polycythemia vera were identified. RESULTS: Our
study showed 70% live births, but only 30% uneventful pregnancies. Fetal
complications were mainly early spontaneous abortions (22%), fetal growth
restriction (15%), and premature delivery (15%). Maternal issues were divided
between thrombosis (15%) and hemorrhages (11%). High rates of preeclampsia and
hemolysis, elevated liver enzymes, and low platelet count syndrome (15%) were
reported. Uterine artery Doppler was performed in 70% pregnancies. Abnormal
Doppler results were found in 43% pregnancies. Pregnancies with high platelet
counts and packed cell volume remaining static or increasing ended with fetal
death and utero-placental dysfunction. According to expert consensus, most of the
pregnancies (67%) could be stratified in the high risk group and had a bad
obstetrical outcome, with 50% standard-risk pregnancies versus 22% high-risk
pregnancies that were uneventful. Higher risk pregnancies were prescribed heparin
and/or interferon alpha in 72%. CONCLUSIONS: The prognosis of these pregnancies
remains very bad and may be improved by a more effective collaboration between
specialists as well as a therapeutic intensification including heparin and
interferon alpha.
PMID- 29945474
TI - Maternal smoking during pregnancy and cord blood DNA methylation: new insight on
sex differences and effect modification by maternal folate levels.
AB - Maternal smoking during pregnancy may affect newborn DNA methylation (DNAm).
However, little is known about how these associations vary by a newborn's sex
and/or maternal nutrition. To fill in this research gap, we investigated
epigenome-wide DNAm associations with maternal smoking during pregnancy in
African American mother-newborn pairs. DNAm profiling in cord (n = 379) and
maternal blood (n = 300) were performed using the Illumina HumanMethylation450
BeadChip array. We identified 12 CpG sites whose DNAm levels in cord blood were
associated with maternal smoking, at a false discovery rate <5%. The identified
associations in the GFI1 gene were more pronounced in male newborns than in
females (P = 0.002 for maternal smoking * sex interaction at cg18146737). We
further observed that maternal smoking and folate level may interactively affect
cord blood DNAm level at cg05575921 in the AHRR gene (P = 5.0 * 10-4 for
interaction): compared to newborns unexposed to maternal smoking and with a high
maternal folate level (>19.2 nmol/L), the DNAm level was about 0.03 lower (P =
3.6 * 10-4) in exposed newborns with a high maternal folate level, but was 0.08
lower (P = 1.2 * 10-8) in exposed newborns with a low maternal folate level. Our
data suggest that adequate maternal folate levels may partly counteract the
impact of maternal smoking on DNAm. These findings may open new avenues of
inquiry regarding sex differences in response to environmental insults and novel
strategies to mitigate their intergenerational health effects through
optimization of maternal nutrition.
PMID- 29945476
TI - Acetabular revision using a Kerboull-type reinforcement device through direct
anterior approach.
AB - BACKGROUND: The direct anterior approach has gained popularity in total hip
arthroplasty (THA) over the past decade. However, there are few reports that
describe the use of this approach for cases of complex revision. The purpose of
this study was to report the surgical procedure and early clinical results of
acetabular revision in the presence of bone defects using a Kerboull-type
reinforcement device through the direct anterior approach. METHODS: Eleven
patients who had undergone acetabular reconstruction using a Kerboull-type
reinforcement device for aseptic or septic loosening bone defects were enrolled.
All procedures were performed using the direct anterior approach on a standard
operating table. The mean age was 71.8 years, the mean period from initial
surgery to revision THA was 14.5 years, and the mean follow-up period was 19.8
months. RESULTS: The Kerboull-type acetabular reinforcement device with cemented
cup combined with allogenic femoral head bone grafts was used in all hips. The
mean operative time and intraoperative blood loss were 148 min and 743 g,
respectively. None of the patients required allogeneic blood transfusion. One
patient required revision surgery 11 months postoperatively because of device
displacement. No other major or minor orthopedic complications were observed.
CONCLUSION: The direct anterior approach allows for less invasive acetabular
reconstruction using a Kerboull-type reinforcement device.
PMID- 29945477
TI - Coexistence of three EGFR mutations in an NSCLC patient: A brief report.
AB - BACKGROUND: The epidermal growth factor receptor (EGFR) represents a molecular
target for tyrosine kinase inhibitors for non-small cell lung cancer (NSCLC)
patients with a mutation in the EGFR gene. Mutations of the EGFR gene that occur
at a single position in NSCLC tissue are found as single, whereas two or more
mutations on the same allele are poorly detected and investigated. PATIENT AND
METHODS: We investigated the presence of the EGFR gene mutations in tumor tissue
by Sanger sequencing and ion torrent sequencing in an NSCLC patient at Stage IV
of disease. RESULTS: We found the presence of three coexisting mutations on the
EGFR gene-two of which on exon 21 are present on the same allele, and the third,
on exon 20, was analyzed by Sanger sequencing of the peripheral blood
lymphocytes. The patient staged as cT4N0M1c (Stage IV) and started afatinib 40 mg
daily 8 months ago, showing a clinical benefit. CONCLUSION: In this report we
describe the case of an NSCLC patient harboring three coexisting mutations on the
EGFR gene, two of which are present on the same allele. This mutation pattern may
represent, for patient progeny, a genetic risk of cancer development. Therefore
it should be possible to obtain screening guidelines to improve the risk
calculation for lung cancer susceptibility in the future.
PMID- 29945478
TI - Prostate cancer grading in 2018: limitations, implementations, cribriform
morphology, and biological markers.
AB - The Gleason grading system is among the most important prognostic factors in
patients with prostate cancer. From the 2005 to the 2014 consensus conferences,
organized by the International Society of Urological Pathology, the morphologic
criteria for the identification of the Gleason patterns were redefined, thus
resulting in the shrinkage of the Gleason pattern 3. This led to the expansion of
the Gleason pattern 4. The newly proposed grade group system reduces the Gleason
scores of prostate cancer to the lowest number, each associated with a unique
behavior from the prognostic point of view. The advantage is that the simplified
system with five groups allows for a more accurate stratification of the patients
in comparison with the Gleason system. Cribriform, fused, ill-defined and
glomeruloid glands are part of the histologic spectrum of the Gleason pattern 4.
Cribriform morphology has a prognosis that is worse in comparison with the other
non-cribriform Gleason 4 patterns. One of the major implications of the
cribriform growth is that it precludes a patient from choosing active
surveillance.
PMID- 29945479
TI - Effect of severe hyperemesis gravidarum on maternal vascular endothelial health:
evaluation of soluble adhesion molecules.
AB - PURPOSE: This study aimed to clarify the effect of severe hyperemesis gravidarum
(sHG) on maternal vascular endothelial health with evaluation of soluble adhesion
molecules. METHOD: The study population consisted of two groups of pregnant
participants between 18 and 35 years of age who were between 5 and 13 weeks of
gestation: sHG group and a healthy control group. A group of 26 participants
whose pregnancies were complicated by sHG was compared with 26 healthy
participants regarding serum levels of the soluble adhesion molecules such as E
selectin, soluble intracellular cell adhesion molecule 1 (sICAM-1), and soluble
vascular cell adhesion molecule one (sVCAM-1), as well as other biochemical
markers. The two groups had similar baseline characteristics. RESULTS: Maternal
baseline characteristics were similar in both groups. Serum levels of E-selectin
(p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were higher in the sHG
group compared with the control group. Higher blood urea nitrogen, creatinine,
and sodium levels, serum osmolarity, and urine density (p < .001, < .001, .006,
.041, and .001, respectively) were also observed in the sHG group compared with
the control group. CONCLUSIONS: The findings of this study indicated that sHG
could impact endothelial cell function and these changes represented hypovolemia
and dehydration caused by severe vomiting. Large-scale studies are required to
understand the clinical importance of this finding regarding the long-term
consequences and underlying mechanisms of elevated sICAM-1, sVCAM-1, and sE
selectin synthesis.
PMID- 29945480
TI - A Longitudinal Investigation of Posttraumatic Growth and Quality of Life in Liver
Transplant Recipients.
AB - BACKGROUND: What does it mean to adjust to a liver transplant? Quality of life
research has offered an impairment model, defining adjustment as the absence of
diagnosed psychological disorder or of limitations in physical functioning.
Recently emerging research on posttraumatic growth testifies the prevalence of
positive life changes following the life-threatening illnesses. The present study
aimed to verify the presence of the posttraumatic growth process in liver
transplant patients and its relationship with traditional quality of life.
METHODS: The research was a longitudinally descriptive study. A sample of 233
liver transplant patients were assessed with the Posttraumatic Growth Inventory
and the Functional Assessment of Chronic Illness Therapy General. RESULTS: Over
50% of patients showed moderate-high levels in all dimensions of the
Posttraumatic Growth Inventory. Further posttraumatic growth is correlated with
the functional and social dimensions of quality of life construct and not with
physical and emotional functioning. CONCLUSION: These results confirmed that
posttraumatic growth is related to a different definition of well-being than the
one traditionally used in the assessment of quality of life. Adjustment to liver
transplant is a complex and systemic process, which requires a multidisciplinary
approach to be able to support and encourages adaptation through all the needed
functional elements. An interesting perspective is offered by the narrative
medicine approach, that highlighted the importance to pay specific attention to
the words and expression used by patients related to changes in life and not only
to traditional words reporting physical status.
PMID- 29945481
TI - Characteristics and incidence of transfusion-associated necrotizing enterocolitis
in the UK.
AB - BACKGROUND AND AIMS: The etiology of necrotizing enterocolitis (NEC) is unclear
and postulated as being multifactorial. It has been suggested that one causative
factor is the transfusion of packed red blood cells (PRBCs) leading to the
disease entity commonly referred to as transfusion-associated NEC (TANEC). TANEC
has been reported in North America but its incidence has not been formally
investigated in the UK. Our aims were to identify the incidence of NEC and TANEC
in tertiary-level UK neonatal units and to describe characteristics of TANEC
cases. MATERIALS AND METHODS: Using strict case definitions for NEC and TANEC, we
undertook a retrospective review to estimate the incidence of TANEC cases
occurring in four UK tertiary-level centers during a 38-month period. RESULTS: Of
8007 consecutive neonatal admissions of all gestations to the four centers, 68
babies went on to develop NEC and all affected infants were of very low birth
weight (VLBW); 34 of these had previously received a transfusion of PRBCs but did
not fit the diagnostic criteria for TANEC, whereas 15 (22%) of the 68 babies with
NEC qualified as TANEC cases. UK cases occurred at an earlier postnatal age than
cases reported in multiple large North American series and were of a lower birth
weight. CONCLUSIONS: We have confirmed the presence of TANEC in the UK VLBW
neonatal population. Its incidence lies within the wide range described in
previous reports of this phenomenon globally, though with some local variation in
characteristics. Further work is needed to clarify causation, pathophysiology,
and possible mechanisms of prevention of TANEC.
PMID- 29945482
TI - The Association Between Lung Recipient Travel Distance and Posttransplant
Survival.
AB - INTRODUCTION: Recipient travel distance may be an unrecognized burden in lung
transplantation. DESIGN: Retrospective single-center cohort study of all adult
(>=18 years) first-time lung-only transplants from January 1, 2010, until
February 28, 2017. Recipient distance to transplant center was calculated using
the linear distance from the recipient's home zip code to the Cleveland Clinic in
Cleveland, Ohio. RESULTS: 569 recipients met inclusion criteria. Posttransplant
graft survival was 85%, 88%, 91%, and 91% at 1 year and 49%, 52%, 57%, and 56% at
5 years posttransplant for recipient travel distances of <=50, >50 to <=250, >250
to <=500, and >500 miles, respectively ( P = .10). DISCUSSION: We found no
significant relationship between recipient travel distance and posttransplant
graft survival. In carefully selected recipients, travel distance is not a
significant barrier to successful posttransplant outcomes which may be important
for patient decision-making and donor allocation policy. These data should be
validated in a national cohort.
PMID- 29945483
TI - Ethical issues experienced during palliative care provision in nursing homes.
AB - BACKGROUND: Palliative care is acknowledged as an appropriate approach to support
older people in nursing homes. Ethical issues arise from many aspects of
palliative care provision in nursing homes; however, they have not been
investigated in this context. AIM: To explore the ethical issues associated with
palliative care in nursing homes in the United Kingdom. DESIGN: Exploratory,
sequential, mixed-methods design. METHODS: Semi-structured interviews with 13
registered nurses and 10 healthcare assistants (HCAs) working in 13 nursing homes
in the United Kingdom were used to explore ethical issues in palliative care. The
'Ethical Issues in Palliative Care for Nursing Homes' instrument was used to
measure the frequency and level of distress arising from ethical issues through a
cross-sectional survey with 69 registered nurses and 129 healthcare assistants.
Data collection occurred between December 2014 and November 2015. Ethical
considerations: Ethical approval was granted by Queen's University's School of
Nursing and Midwifery Research Ethics Committee and governance sought from each
nursing home's manager. FINDINGS: The interviews revealed three themes: ethical
issues in practice; relational issues; and organisational issues. No significant
differences between registered nurses and healthcare assistants were evident,
confirming the patterns emerging from the interviews. Relational issues,
primarily issues with residents and families, occurred most frequently and caused
greater distress. CONCLUSION: The shared environment is key in the experience of
ethical issues; therefore, multidisciplinary education is needed for ethical
decision making in palliative care. Addressing staff knowledge and service
organisation may reduce ethical issues locally and provide a benchmark for global
change.
PMID- 29945484
TI - Quercetin inhibits LPS-induced macrophage migration by suppressing the
iNOS/FAK/paxillin pathway and modulating the cytoskeleton.
AB - The natural flavonoid quercetin has antioxidant, anti-inflammatory, and
anticancer effects. We investigated the effect of quercetin on lipopolysaccharide
(LPS)-induced macrophage migration. Quercetin significantly attenuated LPS
induced inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO)
production in RAW264.7 cells without affecting their viability. Additionally,
quercetin altered the cell size and induced an elongated morphology and enlarged
the vacuoles and concentrated nuclei. Quercetin significantly disrupted the F
actin cytoskeleton structure. Furthermore, quercetin strongly inhibited LPS
induced macrophage adhesion and migration in a dose-dependent manner. Moreover,
quercetin inhibited the LPS-induced expression of p-FAK, p-paxillin, FAK, and
paxillin as well as the cytoskeletal adapter proteins vinculin and Tensin-2.
Therefore, quercetin suppresses LPS-induced migration by inhibiting NO
production, disrupting the F-actin cytoskeleton, and suppressing the FAK-paxillin
pathway. Quercetin may thus have potential as a therapeutic agent for chronic
inflammatory diseases.
PMID- 29945485
TI - Identifying newborns with umbilical cord blood metabolic acidosis by intrapartum
cardiotography combined with fetal ECG ST analysis (STAN): comparison of the new
and old FIGO systems to classify cardiotocograms.
AB - INTRODUCTION: The intrapartum cardiotocography (CTG) classification system by
FIGO in 2015 (FIGO2015) was introduced to simplify CTG interpretation, but it is
not harmonized with the fetal ECG ST analysis (STAN) algorithm from 2007
(STAN2007), which is based on the FIGO CTG system from 1987. The study aimed to
determine time courses and sensitivity between the systems in classifying CTG +
ST events to indicate metabolic acidosis at birth. MATERIAL AND METHODS: Forty
four cases with umbilical cord artery metabolic acidosis were retrieved from a
European multicenter database. CTG patterns and timing of the first occurring
significant ST events were evaluated post hoc in consensus by an expert panel and
sensitivity statistics were performed. Wilcoxon's matched-pairs signed-ranks test
and McNemar's test were used with a two-tailed p < .05 regarded significant.
RESULTS: STAN2007 had a higher sensitivity (73 versus 43%, p = .0002) and alarmed
for metabolic acidosis in mean 34 min earlier than the FIGO2015 system did (p =
.002). In every fourth case, the time difference was >=20 min. CONCLUSIONS: In
this simulation study, surveillance with STAN2007 combined with fetal ECG ST
analysis had a significantly higher sensitivity and would have alarmed for
metabolic acidosis significantly earlier than the new FIGO system would have.
PMID- 29945486
TI - Nudging in nursing.
AB - Nudging is a concept in behavioural science, political theory and economics that
proposes indirect suggestions to try to achieve non-forced compliance and to
influence the decision making and behaviour of groups and individuals.
Researchers in medical ethics are currently discussing whether nudging is
ethically permissible in healthcare. In this article, we examine current
knowledge about how different decisions (rational and pre-rational decisions,
major and minor decisions) are made and how this decision-making process pertains
to patients. We view this knowledge in light of the nursing project and the
ongoing debate regarding the ethical legitimacy of nudging in healthcare. We
argue that it is insufficient to discuss nudging in nursing and healthcare in
light of free will and patient autonomy alone. Sometimes, nurses must take charge
and exhibit leadership in the nurse-patient relationship. From the perspective of
nursing as leadership, nudging becomes a useful tool for directing and guiding
patients towards the shared goals of health, recovery and independence and away
from suffering. The use of nudging in nursing to influence patients' decisions
and actions must be in alignment with the nursing project and in accordance with
patients' own values and goals.
PMID- 29945487
TI - Predictors of early and delayed recovery in peripartum cardiomyopathy: a
prospective study of 52 Patients.
AB - BACKGROUND: Predictors of early or delayed recovery are unclear in peripartum
cardiomyopathy (PPCM). Therefore, we aimed to assess the prognostic value of
serial assessment of clinical, echocardiographic, and biochemical markers in
patients with PPCM. METHODS: Fifty-two consecutive women with PPCM were enrolled
in this prospective study. Each patient underwent transthoracic echocardiography,
B-type natriuretic peptide (BNP) and C-reactive protein (CRP) measurement at
admission, and every 3 months. Early recovery was defined as resolution of heart
failure at 6 months postdiagnosis, delayed recovery was defined if the length of
time required for recovery of left ventricular function was longer than 6 months,
and persistent left ventricular dysfunction (PLVD) was defined as an ejection
fraction of less than 50% at the end of follow-up. RESULTS: Thirty patients
(57.7%) recovered completely, 10 died (19.2%), and 12 (23.1%) had PLVD. There
were no significant differences in baseline BNP and CRP values between patients
who recovered completely and who did not recover. However, patients with complete
recovery were more likely to have a higher left ventricular ejection fraction,
smaller left ventricle end-systolic dimensions at baseline, and lower CRP and BNP
levels at follow-up. Elevated levels of BNP and CRP on follow up at 3 and 6
months were associated with nonrecovery. Third and sixth month BNP values were
significantly lower in patients with rapid recovery, compared to patients with
delayed recovery. Bromocriptine therapy was also associated with early recovery.
CONCLUSIONS: Persistent elevation of plasma CRP and BNP levels at follow-up
portend a slower response or nonrecovery in patients with PPCM. Bromocriptine
therapy was an independent predictor of early recovery.
PMID- 29945489
TI - [Impact of assisted vacations on female caregivers' burden].
AB - : Impact of assisted vacations on female caregivers' burden Abstract. BACKGROUND:
In everyday life, female caregivers experience various burdens due to their
responsibilities and challenges. To relief and regenerate from the stressful
daily routine, assisted vacations may be a viable option. Previously, there were
no empirical findings available that focus on requirements and expectations of
female caregivers. Neither do they provide information about the organisation nor
do they provide information about the implementation of assisted vacations. AIM:
The aim of the study was to collect data concerning the attitudes and
expectations of female caregivers about assisted vacations to identify positive
effects and elements. METHODS: Ten problem-centered interviews with female
caregivers, a group interview with four staff members of a supplier of assisted
vacations, and one expert interview with the management of the supplier were
operated. To analyse the gathered data the qualitative content analysis by 13
2Glaser & Laudel was conducted (2010). RESULTS: A specific anamnesis beforehand
the assisted vacations, a continuous development of trust and relationships as
well as a professional proactive support and take-over of nursing activities can
help female caregivers to enjoy restful and relieving holidays. Six identified
conditions contribute to experience a recreative assisted vacation. CONCLUSIONS:
Staff members who accompany assisted vacations get lots of information about
family caregivers. This could be used for ongoing support of family caregivers
after the assisted vacations to reduce their burden.
PMID- 29945490
TI - In Vivo Efficacy of Histatin-1 in a Rabbit Animal Model.
AB - : Purpose/Aim: Corneal abrasions and nonhealing corneal epithelial defects are
common conditions that cause pain and sometimes are slow to heal. Histatins, a
family of histidine-rich peptides, have been implicated in oral and skin
epithelial wound healing, and have been shown to be effective in vitro in human
corneal epithelial cells. The objective of this study was to test the efficacy of
histatin-1 on corneal epithelial wound healing in rabbits. MATERIALS & METHODS:
Twenty-two (22) rabbits were separated into four treatment groups, each
containing 3-7 rabbits. Treatments included three histatin-1 formulations (0.1
ug/ml. 1 ug/ml, and 10 ug/ml) and one inactive vehicle, one drop given three
times per day. Eight (8) mm circular wounds were created using 0.5 ml of 20%
ethyl alcohol in the right eye of each rabbit. A masked observer photographed
each eye twice daily using slit-lamp biomicrophotography. Wound area was analyzed
by using ImageJ. Statistical analysis was conducted using Graphpad Prism.
RESULTS: Wound recovery was faster in animals given 0.1 ug/ml, 1 ug/ml, and 10
ug/ml when compared to the vehicle solution at 6, 24, and 30 hours after wound
creation (p < 0.01). No adverse events were observed in any eyes. When analyzing
area under the curve, % recovered area was higher overall in the 0.1 ug/ml (p <
0.01), 1 ug/ml (p < 0.01), and 10 ug/ml (p < 0.001) groups when compared to the
vehicle solution. Hourly healing rate was also observed to be faster in the 0.1
ug/ml, 1 ug/ml, and 10 ug/ml groups (p < 0.001) at 24 hours postinjury suggesting
an accelerated healing process as compared to the vehicle group. CONCLUSION: This
study represents the first in vivo experiment evaluating and confirming the
efficacy of topical histatin on the corneal epithelium wound healing. Further
studiesare warranted to better understand the mechanism and safety of topical
histatin-1 in corneal epithelial wound-healing and its potential role for human
disease treatment.
PMID- 29945491
TI - "We Won't Retire Without Skeletons in the Closet": Healthcare-Related Regrets
Among Physicians and Nurses in German-Speaking Swiss Hospitals.
AB - Physicians and nurses are expected to systematically provide high-quality
healthcare in a context marked by complexity, time pressure, heavy workload, and
the influence of nonclinical factors on clinical decisions. Therefore, healthcare
professionals must eventually deal with unfortunate events to which regret is a
typical emotional reaction. Using semistructured interviews, 11 physicians and 13
nurses working in two different hospitals in the German-speaking part of
Switzerland reported a total of 48 healthcare-related regret experiences. Intense
feelings of healthcare-related regrets had far-reaching repercussions on
participants' health, work-life balance, and medical practice. Besides active
compensation strategies, social capital was the most important coping resource.
Receiving superiors' support was crucial for reaffirming professional identity
and helped prevent healthcare professionals from quitting their job. Findings
suggest that training targeting emotional coping could be beneficial for quality
of life and may ultimately lead to lower job turnover among healthcare
professionals.
PMID- 29945493
TI - Reducing the use of inappropriate coagulation testing in emergency general
surgical patients.
AB - Background and aims Indiscriminate coagulation testing in emergency general
surgical patients can lead to inappropriate delay in surgery, cause unnecessary
concern and is associated with significant cost. The British Committee for
Standards in Haematology recommends against coagulation testing to predict peri
operative bleeding risk in unselected patients. Our aim was to assess the
appropriateness of coagulation tests performed in emergency general surgical
patients and evaluate the effect of a series of educational interventions on
clinical practice. Methods and results Appropriate indications for performing
coagulation testing included a positive bleeding history, the presence of liver
disease/cholestasis, sepsis or use of anticoagulants. Initial data on 142
patients were collected over 2 weeks of receiving. Following analysis,
indications for appropriate coagulation testing were highlighted and data were
collected on a further 190 patients. Comparing the audit cycles, we observed a
decrease in the proportion of patients who underwent routine testing (49.3% vs
32.6%; p = 0.002) and inappropriate testing (67% of tests vs 34% of tests; p <
0.001). Despite being highlighted, there was no evidence of improved
documentation of bleeding histories on admission. Conclusions This observational
study suggests that simple educational messages can reduce the inappropriate use
of coagulation screening tests in general surgical emergencies. This seems to
result from clarification of the appropriate surgical indications for coagulation
testing in this group.
PMID- 29945494
TI - Burden of Peripheral Artery Disease in Sub-Saharan Africa and the Caribbean 1990
to 2015.
AB - BACKGROUND: The estimated global prevalence of Peripheral artery disease (PAD)
increased by 24% in span of 10 years (2000-2010) from 164 to 202 million. Despite
scarcity of data on PAD in sub-Saharan Africa (SSA) and the Caribbean, estimates
for PAD from these regions may be helpful for health-care providers. METHODS: The
Global Burden of Disease Study 2015 quantified health loss from hundreds of
diseases using systematic reviews and multilevel computer modeling. Estimated
rates with 95% uncertainty intervals (UI) for PAD (ICD-10 I70.2) were examined
for SSA and the Caribbean and compared to high-income North America (HINA).
Disability-adjusted life years (DALYs) are years of healthy life lost
representing total disease burden by combining years of life lost and years lived
disabled. RESULTS: In 2015, estimated age-standardized DALYs per 100,000 due to
PAD for males were as follows: Caribbean (34, UI: 29-39), HINA (36, UI: 30-42),
and SSA (20, UI: 14-30). In contrast, DALYs in females were as follows: Caribbean
(25, UI: 20-30), HINA (28, UI: 22-36), and SSA (17, UI: 11-26). For both sexes
combined, the rate in Southern SSA was 55 (46-67). This reflects the extremely
high rates in South Africa (males 90, UI: 77-107; females 63, UI: 53-75).
CONCLUSION: Estimated rate of DALYs per 100,000 was lowest in SSA. Within SSA,
the rate in South Africa was highest, exceeding even HINA. Caribbean rates were
intermediate.
PMID- 29945495
TI - A collection of marginalized two-part random-effects models for analyzing medical
expenditure panel data: Impact of the New Cooperative Medical Scheme on
healthcare expenditures in China.
AB - Marginalized two-part random-effects generalized Gamma models have been proposed
for analyzing medical expenditure panel data with excessive zeros. While these
models provide marginal inference on expected healthcare expenditures, the usual
unilateral specification of heteroscedastic variance on one of the two shape
parameters for the generalized Gamma distribution in these models fails to
encompass important special cases within the generalized gamma modeling
framework. In this article, we construct marginalized two-part random-effects
models that employ the log-normal, log-skew-normal, generalized Gamma, Weibull,
Gamma, and inverse Gamma distributions to delineate the spectrum of nonzero
healthcare expenditures in the second part of the models. These marginalized
models supply additional choices for analyzing healthcare expenditure panel data
with excessive zeros. We review the concepts of marginal effect and incremental
effect, and summarize how these effects are estimated. For studies whose primary
goal is to make inference on marginal effect or incremental effect of an
independent variable with respect to healthcare expenditures, we advocate
empirical mean square error criterion and information criteria to choose among
candidate models. Then, we use the proposed models in an empirical analysis to
examine the impact of the New Cooperative Medical Scheme on healthcare
expenditures among older adults in rural China.
PMID- 29945496
TI - Pathogenesis of Renal Injury and Gene Expression Changes in the Male CD-1 Mouse
Associated with Exposure to Empagliflozin.
AB - An increased incidence of renal tubular adenomas and carcinomas was identified in
the 2-year CD-1 mouse carcinogenicity study with empagliflozin (sodium-glucose
transporter 2 inhibitor) in high dose (1,000 mg/kg/day) male mice. A 13-week
mouse renal investigative pathogenesis study was conducted with empagliflozin to
evaluate dose dependency and temporal onset of nonneoplastic
degenerative/regenerative renal tubular and molecular (genes, pathways) changes
which precede neoplasia. Male and female CD-1 mice were given daily oral doses of
0, 100, 300, or 1,000 mg/kg/day (corresponding carcinogenicity study dose levels)
for 1, 2, 4, 8, or 13 weeks. The maximum expected pharmacology with secondary
osmotic diuresis was observed by week 1 at >=100 mg/kg/day in both genders.
Histopathologic kidney changes were first detected after 4 weeks of dosing in the
male 1,000 mg/kg/day dose group, with progressive increases in the incidence
and/or number of findings in this dose group so that they were more readily
detected during weeks 8 and 13. Changes detected starting on week 4 consisted of
minimal single-cell necrosis and minimal increases in mitotic figures. These
changes persisted at an increased incidence at weeks 8 and 13 and were
accompanied by minimal to mild tubular epithelial karyomegaly, minimal proximal
convoluted tubular epithelial cell hyperplasia, and a corresponding increase in
Ki-67-positive nuclei in epithelial cells of the proximal convoluted tubules.
There were no corresponding changes in serum chemistry or urinalysis parameters
indicative of any physiologically meaningful effect on renal function and thus
these findings were not considered to be adverse. Similar changes were not
identified in lower-dose groups in males nor were they present in females of any
dose group. RNA-sequencing analysis revealed male mouse-specific changes in
kidney over 13 weeks of dosing at 1,000 mg/kg/day. Treatment-related changes
included genes and pathways related to p53-regulated cell cycle and
proliferation, transforming growth factor beta, oxidative stress, and renal
injury and the number of genes with significant expression change dramatically
increased at week 13. These treatment-related changes in genes and pathways were
predominant in high-dose males and complemented the observed temporal renal
tubular changes. Overall, these mouse investigative study results support the
role of early empagliflozin-related degenerative/regenerative changes only
observed in high-dose male CD-1 mice as a key contributing feature to a
nongenotoxic mode of renal tumor pathogenesis.
PMID- 29945497
TI - Mandibular premolar migration: two case reports.
AB - Premolar migration is an infrequent and unusual phenomenon. Although several
cases of distal premolar migration have been reported in the literature, the
management of these cases is often challenging and to date, there are no agreed
guidelines regarding best practice. This report describes two cases of distal
migration of a lower second permanent premolar with sequential panoramic imaging
mapping the progress of the teeth as they migrated distally. Cone Beam
Computerised Tomography was subsequently used in one case to locate the migrated
premolars' precise position. We report on one case which was managed with the
surgical removal of the migrated premolar and one case which has been managed
conservatively to date, largely due to patient wishes. Alternative treatment
strategies are also discussed in the following case report.
PMID- 29945498
TI - Expression analysis of Akirin-2, NFkappaB-p65 and beta-catenin proteins in
imatinib resistance of chronic myeloid leukemia.
AB - OBJECTIVE: Chronic myleoid leukemia (CML) is a myeloproliferative disorder
characterized with the constitutive activation of Bcr-Abl tyrosine kinase which
is a target for imatinib, the first line treatment option for CML. Constitutive
activation of NFkappaB and beta-catenin signaling promotes cellular proliferation
and survival and resistance to Imatinib therapy in CML. Akirin-2 is a nuclear
protein which is required for NFkappaB dependent gene expression as a cofactor
and has been linked to Wnt/beta-catenin pathway. The purpose of this study is to
examine Akirin-2, NFkappaB and beta-catenin in imatinib resistance of CML and to
test if any direct physical protein-protein interaction exists between NFkB and
both beta-catenin and Akirin-2. METHODS: RT-PCR and western blot were performed
to determine Akirin-2, NFkappaB-p65 and beta-catenin gene and protein
expressions, Co-immunoprecipitation and chromatin immunoprecipitation analysis
were carried out to detect the direct physical interactions and binding of
NFkappaB-p65 and beta-catenin proteins to MDR1 promoter region, respectively.
RESULTS: beta-catenin and NFkappaB-p65 proteins bound to DNA promoter regions of
MDR1 in imatinib-sensitive and resistant CML cells, whereas any direct protein
protein interaction could not be found between NFkappaB-p65 and Akirin-2 or beta
catenin proteins. Nuclear beta-catenin and NFkappaB-p65 levels increased in
imatinib resistance. Moreover, increased Akirin-2 protein accumulation in the
nucleus was shown for the first time in imatinib resistant CML cells. DISCUSSION:
We show for the first time that Akirin-2 can be a novel biomarker in imatinib
resistance. Targeting Akirin-2, NFkappaB and beta-catenin genes may provide an
opportunity to overcome imatinib resistance in CML.
PMID- 29945499
TI - A transfer learning approach via procrustes analysis and mean shift for cancer
drug sensitivity prediction.
AB - Transfer learning (TL) algorithms aim to improve the prediction performance in a
target task (e.g. the prediction of cisplatin sensitivity in triple-negative
breast cancer patients) via transferring knowledge from auxiliary data of a
related task (e.g. the prediction of docetaxel sensitivity in breast cancer
patients), where the distribution and even the feature space of the data
pertaining to the tasks can be different. In real-world applications, we
sometimes have a limited training set in a target task while we have auxiliary
data from a related task. To obtain a better prediction performance in the target
task, supervised learning requires a sufficiently large training set in the
target task to perform well in predicting future test examples of the target
task. In this paper, we propose a TL approach for cancer drug sensitivity
prediction, where our approach combines three techniques. First, we shift the
representation of a subset of examples from auxiliary data of a related task to a
representation closer to a target training set of a target task. Second, we align
the shifted representation of the selected examples of the auxiliary data to the
target training set to obtain examples with representation aligned to the target
training set. Third, we train machine learning algorithms using both the target
training set and the aligned examples. We evaluate the performance of our
approach against baseline approaches using the Area Under the receiver operating
characteristic (ROC) Curve (AUC) on real clinical trial datasets pertaining to
multiple myeloma, nonsmall cell lung cancer, triple-negative breast cancer, and
breast cancer. Experimental results show that our approach is better than the
baseline approaches in terms of performance and statistical significance.
PMID- 29945500
TI - Investigation of non-hydroxamate scaffolds against HDAC6 inhibition: A
pharmacophore modeling, molecular docking, and molecular dynamics simulation
approach.
AB - Proteins deacetylation by Histone deacetylase 6 (HDAC6) has been shown in various
human chronic diseases like neurodegenerative diseases and cancer, and hence is
an important therapeutic target. Since, the existing inhibitors have hydroxamate
group, and are not HDAC6-selective, therefore, this study has designed to
investigate non-hydroxamate HDAC6 inhibitors. Ligand-based pharmacophore was
generated from 26 training set compounds of HDAC6 inhibitors. The statistical
parameters of pharmacophore (Hypo1) included lowest total cost of 115.63, highest
cost difference of 135.00, lowest RMSD of 0.70 and the highest correlation of
0.98. The pharmacophore was validated by Fischer's Randomization and Test Set
validation, and used as screening tool for chemical databases. The screened
compounds were filtered by fit value ([Formula: see text]), estimated Inhibitory
Concentration (IC[Formula: see text]) ([Formula: see text]), Lipinski's Rule of
Five and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET)
Descriptors to identify drug-like compounds. Furthermore, the drug-like compounds
were docked into the active site of HDAC6. The best docked compounds were
selected having goldfitness score [Formula: see text] and [Formula: see text],
and hydrogen bond interaction with catalytic active residues. Finally, three
inhibitors having sulfamoyl group were selected by Molecular Dynamic (MD)
simulation, which showed stable root mean square deviation (RMSD) (1.6
1.9[Formula: see text]A), lowest potential energy ([Formula: see text][Formula:
see text]kJ/mol), and hydrogen bonding with catalytic active residues of HDAC6.
PMID- 29945501
TI - Introduction to Selected Papers from GIW2017.
PMID- 29945502
TI - Compound property enhancement by virtual compound synthesis.
AB - During drug discovery, drug candidates are narrowed down over several steps to
develop pharmaceutical products. The theoretical chemical space in such steps is
estimated to be [Formula: see text]. To cover that space, extensive virtual
compound libraries have been developed; however, the compilation of extensive
libraries comes at large computational cost. Thus, to reduce the computational
cost, researchers have constructed custom-made virtual compound libraries that
focus on target diseases. In this study, we develop a system that generates
virtual compound libraries from input compounds. When a user inputs a compound,
the system recursively applies virtual synthetic reaction rules to the compound
to improve its properties. The synthetic pathway can also be traced by the user
because the reaction rules in this system are based on real organic synthesis
reactions. This system has useful functions for effective drug design, such as
structural preservation, allowing the substructures necessary for potency to be
maintained. In this paper, to confirm the effect of directional reaction sets, we
applied the reaction sets to 100 compounds. Moreover, to confirm that the system
can reproduce real synthetic pathways, the synthetic pathways of Ibuprofen and
Ofloxacin were explored by inputting isobutyl benzene and 7,8-difluoro-2,3
dihydro-3-methyl-4H-benzoxazine. This application is available at the following
URL: http://enh.sekijima-lab.org .
PMID- 29945503
TI - Proposing drug fragments for dengue virus NS5 protein.
AB - Dengue fever is a febrile illness caused by Dengue Virus, which belongs to the
Flaviviridae family. Among its proteome, the nonstructural protein 5 (NS5) is the
biggest and most conserved. It has a primer-independent RNA-dependent RNA
polymerase (RdRp) domain at its C-Terminus. Zou et al. studied the biological
relevance of the two conserved cavities (named A and B) within the NS5 proteins
of dengue virus (DENV) and West Nile Virus (WNV) using mutagenesis and revertant
analysis and found four mutations located at cavity B having effects on viral
replication. They recommended Cavity B, but not Cavity A as a potential target
for drugs against flavivirus RdRp. In this study, we virtually screened the
MayBridge drug fragments dataset for potential small molecule binders of cavity B
using both AutoDock Vina, the standard docking tool, and QuickVina 2, our
previously developed tool. We selected 16 fragments that appeared in the top 100
docking results of each of the representative structures of NS5. Visual
inspection suggests that they have reasonable binding poses. The 16 predicted
fragments are plausible drug candidates and should be considered for further
validation, optimization, and linking to come up with a suitable inhibitor of
dengue virus.
PMID- 29945504
TI - Rotational Thromboelastometry Rapidly Predicts Thrombocytopenia and
Hypofibrinogenemia During Neonatal Cardiopulmonary Bypass.
AB - BACKGROUND: Thrombocytopenia and hypofibrinogenemia during neonatal
cardiopulmonary bypass (CPB) contribute to bleeding and morbidity. Rotational
thromboelastometry (ROTEM) is a viscoelastic assay with a rapid turnaround time.
Data validating ROTEM during neonatal cardiac surgery remain limited. This study
examined perioperative hemostatic trends in neonates treated with standardized
platelet and cryoprecipitate transfusion during CPB. We hypothesized that ROTEM
would predict thrombocytopenia, hypofibrinogenemia, and the correction thereof.
METHODS: Forty-four neonates undergoing CPB were included in this prospective
observational study. Blood samples were obtained at Baseline, On CPB, Post-CPB,
and Postoperative. The ROTEM analysis included extrinsically activated (Extem)
and fibrinogen-specific (Fibtem) assays. Platelet-specific thromboelastometry
(Pltem) values were calculated. Platelet and cryoprecipitate transfusion was
initiated prior to termination of CPB. RESULTS: Platelet count and Extem
amplitude decreased significantly On CPB ( P < .0001), increased significantly
Post-CPB ( P < .0001), and Postoperative values were not significantly different
from Baseline. Extem amplitude at 10 minutes (A10) > 46.5 mm (AUC = 0.941) and
Pltem A10 > 37.5 mm [area under curve (AUC) = 0.960] predicted platelet count >
100 * 103/MUL, and they highly correlated with platelet count ( R = 0.89 and R =
0.90, respectively). Fibrinogen concentration and Fibtem amplitude decreased
significantly On CPB ( P <= .0001) and normalized after cryoprecipitate
transfusion. Fibtem A10 > 9.5 mm predicted fibrinogen >200 mg/dL (AUC = 0.817),
but it correlated less well with fibrinogen concentration ( R = 0.65).
CONCLUSIONS: ROTEM analysis during neonatal cardiac surgery is sensitive and
specific for thrombocytopenia and hypofibrinogenemia, identifying deficits within
10 minutes. Platelet and cryoprecipitate transfusion during neonatal CPB
normalizes platelet count, fibrinogen level, and ROTEM amplitudes.
PMID- 29945505
TI - Kawashima by Fenestrated Hemi-Fontan for Palliation Following Prior Stage I
Norwood Operation.
AB - Single ventricle patients with interrupted inferior vena cava (IVC) and azygos
continuation to the superior vena cava (SVC) are typically palliated with a
bidirectional cavopulmonary shunt (BCPS), known as the Kawashima operation in
this setting. Because the volume of venous blood directed to the pulmonary
arteries is substantially greater in the presence of interrupted IVC, Kawashima
procedures are commonly delayed to older age compared to other single ventricle
patients undergoing BCPS. We report two young infant single ventricle patients
with interrupted IVC and azygos continuation to the SVC who underwent stage I
Norwood procedures for initial palliation. In both cases, a fenestrated hemi
Fontan procedure achieved successful Kawashima circulations.
PMID- 29945506
TI - Similar Interstage Outcomes for Single Ventricle Infants Palliated With an
Aortopulmonary Shunt Compared to the Norwood Procedure.
AB - BACKGROUND: Interstage outcomes for single ventricle infants following Norwood
operation have been well studied, showing significant mortality. Other single
ventricle infants require only an aortopulmonary shunt. The aim of the study was
to describe the interstage outcomes of this group compared to Norwood patients
and identify risk factors for mortality. METHODS: A single-center retrospective
cohort review was performed in patients who underwent a Norwood operation
(Norwood) or aortopulmonary shunt (Shunt) during 2000 to 2011 and survived to
discharge. Hybrid or pulmonary artery banding patients were excluded. Univariate
comparison was made between Norwood and Shunt patients as well as a Shunt
subgroup analysis. RESULTS: A total of 486 patients (368 Norwood and 118 Shunt)
were included. Norwood and Shunt patients were similar in terms of preterm birth,
surgery weight, and stage 1 complications. Shunt patients were more likely to be
female, have an extracardiac or genetic anomaly, and have a shorter hospital
length of stay compared to the Norwood patients (all P < .0001). No significant
difference in interstage mortality was seen between the Shunt and Norwood
patients (6.8% vs 11.1%, respectively; P = .17). Stage 2 mortality was also
similar (Shunt 4.6% vs Norwood 7.8%; P = .25). In the Shunt patients, those who
died during interstage weighed less at surgery (2.7 [0.7] kg vs 3.3 [0.7] kg, P =
.03) and were more likely to have arrhythmias (50% vs 12%, P = .01), compared to
survivors. CONCLUSIONS: Shunt patients have an interstage mortality that is not
significantly less than Norwood patients. Lower weight at surgery and arrhythmias
are risk factors for interstage death in Shunt patients.
PMID- 29945507
TI - Surgical Closure of Patent Ductus Arteriosus in Premature Neonates Weighing Less
Than 1,000 grams: Contemporary Outcomes.
AB - OBJECTIVE: The safety of surgical closure of patent ductus arteriosus (PDA) in
very low birth weight premature neonates has been questioned because of
associated morbidities. However, these studies are vulnerable to significant bias
as surgical ligation has historically been utilized as "rescue" therapy. The
objective of this study was to review our institutions' outcomes of surgical PDA
ligation. METHODS: All neonates with operative weight of <=1.00 kg undergoing
surgical PDA ligation from 2003 to 2015 were analyzed. Records were queried to
identify surgical complications, perioperative morbidity, and mortality. Outcomes
included pre- and postoperative ventilator requirements, pre- and postoperative
inotropic support, acute kidney injury, surgical complications, and 30-day
mortality. RESULTS: One hundred sixty-six preterm neonates underwent surgical
ligation. One hundred twenty-one (70.3%) had failed indomethacin closure. One
hundred sixty-four (98.8%) patients required mechanical ventilation prior to
surgery. At 17 postoperative days, freedom from the ventilator reached 50%. Of
109 (66.4%) patients requiring prolonged preoperative inotropic support, 59
(54.1%) were liberated from inotropes by postoperative day 1. Surgical morbidity
was encountered in four neonates (2.4%): two (1.2%) patients had a postoperative
pneumothorax requiring tube thoracostomy, one (0.6%) patient had a recurrent
laryngeal nerve injury, and one (0.6%) patient had significant intraoperative
bleeding. The 30-day all-cause mortality was 1.8% (n = 3); no deaths occurred
intraoperatively. CONCLUSION: In this retrospective investigation, surgical PDA
closure was associated with low 30-day mortality and minimal morbidity and
resulted in rapid discontinuation of inotropic support and weaning from
mechanical ventilation. Given the safety of this intervention, surgical PDA
ligation merits consideration in the management strategy of the preterm neonate
with a PDA.
PMID- 29945508
TI - Single Ventricle and Total Anomalous Pulmonary Venous Connection: Implications of
Prenatal Diagnosis.
AB - BACKGROUND: Single ventricle (SV) patients with total anomalous pulmonary venous
connection (TAPVC) are at high risk. Given the limited published data available,
we examined outcomes and the implications of a prenatal diagnosis of SV/TAPVC.
METHODS: A single-center, retrospective review was performed in neonates with
SV/TAPVC from 1998 to 2014, identified through institutional databases. Patient
demographic, perioperative, and follow-up data were collected. RESULTS: Thirty
four eligible infants with SV/TAPVC were identified (mean birth weight: 3.0 kg).
The TAPVC types were supracardiac (59%), infracardiac (21%), mixed (12%), and
cardiac (9%). Heterotaxy syndrome was present in 25 (74%) infants. A prenatal
diagnosis of SV was made in 26 (76%) infants, with TAPVC identified in 12 (35%).
Seventeen (50%) had obstructed TAPVC within the first 48 hours of life; 7 of
these patients had obstructed TAPVC identified prenatally. There were two
preoperative deaths. Overall survival for the cohort was 65% at 1 year and 50% at
3 years. Survival in the obstructed group was significantly worse compared to the
unobstructed group (47% vs 81% at 1 year; 27% vs 73% at 3 years, P = .01).
Obstructed TAPVC and a prenatal prediction of obstructed TAPVC were significantly
associated with postoperative mortality ( P = .01 and .03, respectively).
CONCLUSIONS: Patients with SV/TAPVC remain a high-risk group, with obstructed
TAPVC a significant risk factor for mortality. Prenatal diagnosis of TAPVC in SV
patients is challenging, but given those with obstructed TAPVC are especially at
high risk, improved prenatal diagnostic techniques in this group may enhance
counseling/delivery planning.
PMID- 29945509
TI - Ubiquitin C-Terminal Hydrolase 1 and Phosphorylated Axonal Neurofilament Heavy
Chain in Infants Undergoing Cardiac Surgery: Preliminary Assessment as Potential
Biomarkers of Brain Injury.
AB - BACKGROUND: There are no reliable markers to assess brain injury in neonates
following cardiac surgery. We examine ubiquitin C-terminal hydrolase 1 (UCHL1)
and phosphorylated axonal neurofilament heavy chain (pNF-H), neuronal-specific
biomarkers released following axonal and cortical injury, in neonates undergoing
cardiac surgery involving cardiopulmonary bypass (CPB) and deep hypothermic
circulatory arrest (DHCA). METHODS: Twenty-six patients younger than three months
were prospectively enrolled (CPB only, n = 12 and DHCA, n = 14). Healthy newborns
(n = 22) served as the control. Blood samples were collected preoperatively and
postoperatively upon intensive care unit admission (hour 0) and subsequently at
12, 24, 36, and 48 hours. Serum was tested for UCHL1 and pNF-H using enzyme
linked immunosorbent assay. Concomitant arterial blood gas, lactate, and cerebral
near-infrared spectroscopy (NIRS) monitoring were performed. RESULTS: Ubiquitin C
terminal hydrolase 1 showed a significant rise at 0 hours in the DHCA group
compared to baseline (74.9 +/- 13.7 pg/mL vs 33.9 +/- 37.3 pg/mL, P < .0001).
Levels returned to baseline at 12 hours. There was an early rise in UCHL1 at 0
hours in the CPB group, P = .09. Phosphorylated axonal neurofilament heavy chain
was decreased at 0 hours in both the CPB and DHCA groups compared to baseline, P
= .06. There was no difference between control and baseline levels of UCHL1 ( P =
.9) or pNF-H ( P = .77). Decreased NIRS was observed in the DHCA group at 0 hours
(57.3 +/- 10.5) versus baseline (64.2 +/- 12.3), but not significant ( P = .21).
There was no correlation between biomarkers and NIRS at 0 hours. CONCLUSION: A
rapid rise in UCHL1 levels was observed in the DHCA group, suggesting that it may
be a marker for acute brain injury. Follow-up with neurodevelopmental studies is
ongoing.
PMID- 29945510
TI - Digital Design and 3D Printing of Aortic Arch Reconstruction in HLHS for Surgical
Simulation and Training.
AB - PURPOSE: Patients with hypoplastic left heart syndrome (HLHS) present a diverse
spectrum of aortic arch morphology. Suboptimal geometry of the reconstructed
aortic arch may result from inappropriate size and shape of an implanted patch
and may be associated with poor outcomes. Meanwhile, advances in diagnostic
imaging, computer-aided design, and three-dimensional (3D) printing technology
have enabled the creation of 3D models. The purpose of this study is to create a
surgical simulation and training model for aortic arch reconstruction.
DESCRIPTION: Specialized segmentation software was used to isolate aortic arch
anatomy from HLHS computed tomography scan images to create digital 3D models.
Three-dimensional modeling software was used to modify the exported segmented
models and digitally design printable customized patches that were optimally
sized for arch reconstruction. EVALUATION: Life-sized models of HLHS aortic arch
anatomy and a digitally derived customized patch were 3D printed to allow
simulation of surgical suturing and reconstruction. The patient-specific
customized patch was successfully used for surgical simulation. CONCLUSIONS:
Feasibility of digital design and 3D printing of patient-specific patches for
aortic arch reconstruction has been demonstrated. The technology facilitates
surgical simulation. Surgical training that leads to an understanding of optimal
aortic patch geometry is one element that may potentially influence outcomes for
patients with HLHS.
PMID- 29945511
TI - A Letter to the Resident Starting My Service....
PMID- 29945513
TI - Vasopressin Is No Inotrope.
PMID- 29945512
TI - History of the World Society for Pediatric and Congenital Heart Surgery: The
First Decade.
AB - The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) is the
largest professional organization in the world dedicated to pediatric and
congenital heart surgery. The purpose of this article is to document the first
decade of the history of WSPCHS from its formation in 2006, to summarize the
current status of WSPCHS, and to consider the future of WSPCHS. The WSPCHS was
incorporated in Canada on April 7, 2011, with a head office in Montreal, Canada.
The vision of the WSPCHS is that every child born anywhere in the world with a
congenital heart defect should have access to appropriate medical and surgical
care. The mission of the WSPCHS is to promote the highest quality comprehensive
cardiac care to all patients with congenital heart disease, from the fetus to the
adult, regardless of the patient's economic means, with an emphasis on excellence
in teaching, research, and community service.
PMID- 29945515
TI - Perspective Regarding Postoperative Care Following Pediatric Heart Surgery.
PMID- 29945514
TI - Role of Negative Pressure Wound Care and Hyperbaric Oxygen Therapy for Sternal
Wound Infections After Pediatric Cardiac Surgery.
AB - BACKGROUND: Sternal wound infections after pediatric cardiac surgery are uncommon
but can be morbid. METHODS: We describe an institutional protocol for complicated
sternal wounds utilizing hyperbaric oxygen therapy (HBO) and negative pressure
wound therapy (NPWT). PARTICIPANTS: A retrospective chart review (2001-2013) of
4,028 pediatric cardiac operations in 3,264 patients less than 18 years of age.
RESULTS: Fifty-three patients (1.62%; 53/3,264) were diagnosed with clinical
sternal wound infections. There were 27 (50.9%) males and 26 (49.1%) females.
Thirty-seven (69.8%) patients received antibiotics and/or debridement; sixteen
(30.2%) patients had more complicated infections requiring NPWT and/or HBO
therapy. The time to heal for wounds treated with HBO and HBO + NPWT was a mean
of 43.75 (+/-24.27) days (range: 21-98 days; median: 35 days). Among all infected
patients, the time from diagnosis of the infection to resolution of the infection
for all survivors was 7 to 98 days (mean: 26.41 days; median: 21 days). Forty
eight (90.6%) patients completely healed their wounds, and 45 (84.9%) patients
are currently alive. Thirty-eight patients had a cyanotic cardiac diagnosis and
15 had an acyanotic cardiac diagnosis. The most common bacteria isolated from the
blood or wound cultures was Staphylococcus aureus. Six of 53 patients died.
Causes of death are as follows: three from respiratory failure, one from sepsis,
one from hypoxic ischemic encephalopathy, and one from exsanguination leading to
cardiac arrest Conclusions: Complicated sternal wound infections after pediatric
cardiac surgery refractory to antibiotic therapy and/or debridement can be
successfully treated with NPWT and/or HBO therapy.
PMID- 29945516
TI - Strengthening International Collaboration in Congenital Heart Surgery.
AB - This paper was presented by the author at the 2016 biannual scientific meeting in
Abu dhabi of the World Society for Pediatric and Congenital Heart Surgery as his
incoming presidential address. In addition to listing the accomplishments of the
World Society including several successful international scientific meetings and
regional meetings, the Society has established the only journal devoted to
congenital heart surgery and is in the process of establishing the new World
Society database. The mission statement of the World Society emphasizes equitable
global management of patients with congenital heart disease and includes an
emphasis on excellence in education, research and community service. The Society
will promote international exchange of trainees in congenital heart surgery, the
facilitation of international teaching and treatment missions as well as a system
for global certification of congenital heart surgeons to facilitate international
movement of surgeons to areas of greatest need.
PMID- 29945517
TI - Thoracotomy for Stage I Lung Cancer Resections: A Procedure Past Its Time.
PMID- 29945518
TI - Comparing Modalities Using the National Cancer Database: Concerns With Rajyaguru
et al.
PMID- 29945519
TI - Reply to E.L. Pollom et al, N. Ohri et al, A. Fiorentino et al, D.R. Wahl et al,
N. Kim et al, J. Boda-Heggemann et al, S. Rana et al, N. Sanuki et al, J.R. Olsen
et al, G.L. Smith et al, and A. Shinde et al.
PMID- 29945520
TI - Comparing Ablative Modalities for Hepatocellular Carcinoma: Cautions in
Interpreting Big Data.
PMID- 29945521
TI - Cross-Modality Comparisons Between Radiofrequency Ablation and Stereotactic Body
Radiotherapy for Treatment of Hepatocellular Carcinoma: Limitations of the
National Cancer Database.
PMID- 29945522
TI - Are Head-to-Head Comparisons Between Radiofrequency Ablation and Stereotactic
Body Radiotherapy Really Necessary for Localized Hepatocellular Carcinoma?
PMID- 29945523
TI - What Role Does Locally Ablative Stereotactic Body Radiotherapy Play Versus
Radiofrequency Ablation in Localized Hepatocellular Carcinoma?
PMID- 29945524
TI - Correspondence on Rajyaguru et al.
PMID- 29945525
TI - Survival Analyses Are Flawed When Neglecting Barcelona Clinic Liver Cancer
Staging.
PMID- 29945526
TI - Casual Causality: Does Radiofrequency Ablation Really Prolong Survival After
Treatment of Localized Hepatocellular Carcinoma?
PMID- 29945527
TI - Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Hepatocellular
Carcinoma: Caution When Interpreting Observational Data.
PMID- 29945528
TI - Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Hepatocellular
Carcinoma: No Way Out Without a Randomized Trial?
PMID- 29945529
TI - Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Localized
Hepatocellular Carcinoma: Does Radiation Dose Make a Difference?
PMID- 29945530
TI - The use of sacubitril/valsartan in anthracycline-induced cardiomyopathy: A mini
case series.
AB - Background Sacubitril/valsartan has been shown to significantly reduce
cardiovascular mortality and hospitalizations due to heart failure in adult
patients with reduced ejection fraction when compared to enalapril. To the best
of our knowledge, the combination of sacubitril (neprilysin inhibitor) and
valsartan (angiotensin receptor blocker) has not been evaluated in patients with
chemotherapy-induced cardiomyopathy, as these patients were excluded from the
recent pivotal trial, PARADIGM-HF. However, current guidelines for the evaluation
and management of cardiovascular complications of cancer therapy, published by
the Canadian Cardiovascular Society, direct clinicians to the Canadian
Cardiovascular Society Heart Failure Guidelines for the management of cancer
patients who develop clinical heart failure or an asymptomatic decline in left
ventricular ejection fraction (e.g. >10% reduction from baseline or left
ventricular ejection fraction <53%), which could include the use of
sacubitril/valsartan. Methods Retrospective descriptive comparative case study of
two patients treated with sacubitril/valsartan. Results We present data from two
patients who experienced anthracycline-induced cardiomyopathy and were
successfully managed with sacubitril/valsartan after suboptimal responses to
traditional evidence-based heart failure therapies. Both patients demonstrated
some recovery of function and normalization of N-terminal pro B-type natriuretic
peptide levels. Sacubitril/valsartan was well tolerated with minimal side
effects. To date, neither patient has required hospitalization or additional
clinic interventions for heart failure. Conclusions While further large scale
studies are required to determine a comprehensive safety and efficacy profile, we
report two cases of anthracycline-induced cardiomyopathy survivors managed with
sacubitril/valsartan with minimal side effects and no hospitalizations.
PMID- 29945532
TI - Letermovir associated hepatic transaminitis: A case report.
AB - Letermovir is an antiviral agent recently approved by the Food and Drug
Administration for prophylaxis of cytomegalovirus infection in adult patients
that are cytomegalovirus-seropositive recipients of an allogeneic hematopoietic
stem cell transplant. Liver toxicity was not observed in the clinical trials that
led to its approval. This report highlights a case of letermovir associated
transaminitis with successful rechallenge through peak and recovery of the
hepatic serum enzymes. Because there is currently no published evidence to
support the adverse event, the temporal relationship and response to rechallenge
that was observed is essential to establishing the probable causality in this
case.
PMID- 29945531
TI - Significant drug interaction between voriconazole and dexamethasone: A case
report.
AB - Background Voriconazole is extensively metabolized by the CYP450 isoenzymes 2C19
and 3A4 and to a lesser extent by CYP2C9; therefore, any medication that affects
this pathway can alter its plasma concentration. Treatment failure can probably
occur if subtherapeutic levels are achieved. Case description A 32-year-old woman
who suffered from acute lymphoblastic leukemia was admitted and received
treatment with vincristine and dexamethasone. After several days, to control her
fever, based on two consecutive positive serum galactomannan test results,
voriconazole as an antifungal agent was added to Aspergillus infection treatment.
Through the first week after voriconazole initiation, its plasma concentrations
were subtherapeutic. The most suspicious medication for interaction was
dexamethasone, which can induce CYP450 isoenzymes and reduce plasma
concentration. Conclusion As a result of the narrow therapeutic window of
voriconazole and the relationship between efficacy and plasma concentration of
azoles, therapeutic drug monitoring of voriconazole in patients receiving a high
dose of glucocorticoids is recommended, in order to achieve optimal response to
treatment and toxicity reduction. Further studies regarding the interaction
between voriconazole and dexamethasone to prevent clinically relevant
interactions should be considered.
PMID- 29945533
TI - Does oncology research need to slow down a little bit?
PMID- 29945534
TI - Efficacy of bevacizumab and temozolomide therapy in locally advanced, recurrent,
and metastatic malignant solitary fibrous tumour: A population-based analysis.
AB - Background Patients with locally advanced, recurrent or metastatic solitary
fibrous tumour are often treated with bevacizumab and temozolomide based on the
clinical efficacy reported in a case series of 14 patients. Given the rarity of
solitary fibrous tumour, large trials are not feasible. We report the efficacy of
this regimen based on a population-based analysis. Methods This was a population
based retrospective, multi-centre analysis using patient data from a provincial
cancer registry and treatment database. Cases from June 2006 through October 2016
were identified for patients receiving bevacizumab and temozolomide for locally
advanced, recurrent or metastatic solitary fibrous tumour or hemangiopericytoma,
which is sometimes used to describe tumours arising from the meninges. The
primary outcome was overall response rate. Secondary outcomes included time to
response, progression free survival and overall survival estimated using the
Kaplan-Meier method. Results Fourteen patients were identified: median age 59
(range 44-70), male 78.6%. Diagnoses were solitary fibrous tumour in 10 (71.4%)
and hemangiopericytoma in four (28.6%), with metastatic disease in 10 (72.7%)
patients. The most common primary sites were meninges in four (28.6%) and pelvis
in three (21.4%) patients. The median follow-up was 15.5 months, with median
treatment of four months. Overall response rate was 21.4% (no complete response,
3 partial response), with median time to response of four months. Median
progression free survival, six-month progression free survival and overall
survival were 17 months, 65.0%, and 45 months, respectively. Conclusions Efficacy
of bevacizumab and temozolomide in solitary fibrous tumour appeared to be similar
to that previously reported. Our findings confirmed that bevacizumab and
temozolomide is an effective and tolerated treatment for this patient population.
PMID- 29945535
TI - Real world evidence: Abiraterone use post-docetaxel in metastatic castrate
resistant prostate cancer.
AB - Objectives The COU-AA-301 trial demonstrated that in men with metastatic castrate
resistant prostate cancer using abiraterone post-docetaxel increased overall
survival. This study aims to assess this conclusion in a real world context.
Design Retrospective chart review of a provincial Pharmacy BDM Database (a
pharmacy dispensing software) and a provincial Electronic Chart (ARIA).
Dispensing data, information on the state of the disease before and after
abiraterone use, and information regarding effects of abiraterone were gathered.
Setting Cancer centers in Alberta, Canada. Patients Metastatic castrate-resistant
prostate cancer (CRPC) patients on abiraterone outside of a clinical trial who
have previously had docetaxel chemotherapy for CRPC between February 2012 and May
2014. Primary outcome Overall survival from the time of abiraterone initiation.
Results Overall survival increase of 17 months was consistent with the survival
increase of 14.8 months observed in the pivotal trial. Conclusion Abiraterone is
a valuable therapy post-docetaxel for metastatic CRPC, as in a real world context
it demonstrated an increase in overall survival that was consistent with the
findings of the clinical trial despite including a patient population of older
age and lower performance status.
PMID- 29945536
TI - Effect of water glass coating of tricalcium phosphate on in vitro cellular
proliferation and osteogenic differentiation.
AB - Background In this study, the properties of the water glass (WG, sodium-silicate
glass) were utilized to control the biodegradability of the beta tricalcium
phosphate materials by the WG coating on the tricalcium phosphate disc surface
with various coating thickness, chemistry, and heat-treatment. Methods Four types
of disc specimens were prepared. A sample group A consisted of pure
hydroxyapatite (HA) as a negative resorption control; a sample group B consisted
of pure beta tricalcium phosphate as a positive resorption control; a sample
group C consisted of beta tricalcium phosphate coated with WG as an early
resorption model; and a sample group D consisted beta tricalcium phosphate coated
with WG and heat-treated at 500 degrees C as a delayed resorption model. Using
human bone marrow-derived mesenchymal stem cells, for the analysis of cellular
attachment and proliferative activity, 4-6-Diamidino-2-Phenylindole fluorescence
technique was used. For the analysis of osteteogenic differentiation, alkaline
phospastase (ALP) activity was measured. Results The mean z-scores of four groups
(A, B, C, and D) in cellular attachment at 4 h after seeding were -1.21, -0.15,
0.42, and 0.94, respectively, and statistically significantly different in all
groups respectively. Seven days after seeding, the mean z-scores of cellular
proliferation were 1.97, 0.71, 1.48, and 1.83 in the four groups, respectively.
The mean z-scores of the ALP activity per the mean z-scores of cell numbers of
respective groups on the seventh day were 0.40, -1.51, 0.12, and 0.06,
respectively, in four groups. Conclusion Initial cellular attachment is better on
beta tricalcium phosphate than on HA and is enhanced by WG coating, especially
with sintering at the high temperature. Cellular proliferation is considered to
be increased by maintaining its attachment site through reduced dissolution of
beta tricalcium phosphate by WG coating. Osteogenic differentiation in in-vitro
study on the WG-coated beta tricalcium phosphate is thought to be as the result
of increased silicon ion release from the WG.
PMID- 29945537
TI - Evaluation of a vaccine passport to improve vaccine coverage in people living
with HIV.
AB - An increased risk of vaccine-preventable infections (VPIs) is seen in people
living with HIV (PLWH), and current vaccine coverage and immunity is variable.
Vaccine passports have the potential to improve vaccine coverage. The objective
was to assess how successful a vaccine passport was in improving vaccine coverage
in PLWH. Baseline immunity to VPIs was established in PLWH attending a single HIV
clinic and vaccinations required were determined based on the BHIVA Vaccination
Guidelines (2015). The passport was completed and the PLWH informed about
additional vaccines they should obtain from primary care. After 6-9 months the
passport was reviewed including confirmation if vaccines were given. PLWH
satisfaction with the system was evaluated by a survey. Seventy-three PLWH
provided sufficient data for analysis. At baseline significant proportions of
PLWH were not immune/unvaccinated to the main VPIs, especially human
papillomavirus, pneumococcus and measles. After the passport was applied immunity
improved significantly (56% overall, p < 0.01) for most VPIs; however, full
coverage was not achieved. The system was popular with PLWH. The passport was
successful in increasing vaccination coverage although full or near-full coverage
was not achieved. A more successful service would probably be achieved by
commissioning English HIV clinics to provide all vaccines.
PMID- 29945538
TI - Anthropometric definitions for antiretroviral-associated lipodystrophy derived
from a longitudinal South African cohort with serial dual-energy X-ray
absorptiometry measurements.
AB - The development of lipodystrophy is associated with the long-term use of
antiretroviral therapy (ART). We assessed agreement between patient-reported
lipodystrophy and body composition measures using dual-energy X-ray
absorptiometry (DXA) and developed objective measures to define lipoatrophy and
lipohypertrophy in black South Africans. One hundred and eighty-seven ART-naive
HIV-infected adults were enrolled in a 24-month longitudinal study. Self-reported
information on regional fat loss and fat gain, anthropometry, and DXA measures
were collected at baseline, three, six, 12, 18, and 24 months after starting ART.
Receiver operating characteristic curves were used to describe the performance of
anthropometric variables using change in limb and trunk fat measured by DXA, as
the reference standard. The proportion of men and women who developed lipoatrophy
and lipohypertrophy increased over the 24-month period, with lipoatrophy
occurring more frequently in men (21% versus 10%). In women, lipoatrophy was best
determined by thigh skinfold thickness (80.3% correctly classified) and mid-arm
circumference (77.6% correctly classified). None of the anthropometric measures
performed well for defining lipoatrophy in men. Anthropometric measures performed
well for defining lipoatrophy in women, but not lipohypertrophy.
PMID- 29945539
TI - Emerging sexually transmitted viral infections: 2. Review of Zika virus disease.
AB - A sudden increase in the number of newborn infants with microcephaly in Brazil in
2015 brought Zika virus (ZIKV), a less-known infection, to public attention. The
rapid increase in the number of cases across the Americas and the devastating
complications of infection with ZIKV highlighted the gravity of the situation.
Within a relatively short period of time, our knowledge of this infection has
significantly increased. This includes the realisation that ZIKV can be sexually
transmitted. The aim of the present article is to provide a concise summary on
this novel sexually transmitted infection linked to human birth defects and
Guillain-Barre Syndrome. According to World Health Organization, individuals
living outside areas of ZIKV mosquito transmission where one or both partners
have been exposed to ZIKV should abstain from sex or have sex with condoms for at
least six months after the last day of possible exposure.
PMID- 29945540
TI - Age and racial disparities in substance use and self-reported viral suppression
among men who have sex with men with HIV.
AB - HIV disproportionately affects men who have sex with men (MSM). Substance use is
common among people living with HIV and may affect antiretroviral therapy
adherence. Nevertheless, research examining the association between substance use
and viral suppression is lacking. The aims of this study were to determine the
association between substance use and self-reported viral suppression, and by age
and race among MSM living with HIV. Data were obtained from 309 HIV-positive MSM.
Logistic regression was used to determine the association between substance use
and self-reported viral suppression at baseline, and by age and race.
Approximately 67% of participants reported they were virally suppressed. After
adjusting for sociodemographics, every increase in substance use score was
associated with a 7% decrease in the odds of reporting viral suppression (odds
ratio [OR]: 0.93; 95% confidence interval [CI]: 0.89-0.98; p = 0.003). The
negative association between substance use and self-reported viral suppression
remained statistically significant among MSM aged 25-34 years (OR = 0.89; 95% CI:
0.79-1.00; p = 0.041) and statistically significant for Black MSM (OR = 0.92; 95%
CI: 0.86-0.98; p = 0.009). Intervention programs for MSM living with HIV aimed at
improving viral suppression should address substance use and consider the
differences by age and race.
PMID- 29945541
TI - Factors associated with linkage to care for HIV patients in Tajikistan.
AB - There is a growing human immunodeficiency virus (HIV) epidemic in Tajikistan.
This paper presents factors associated with linkage to HIV care among people aged
15 years and older in Tajikistan. This retrospective cross-sectional study used
the Tajikistan Ministry of Health HIV registry data from patients diagnosed with
HIV at age 15 years or older from 2000 to 2016. Chi squared tests and logistic
regression models tested factors associated with linkage to care. A multivariable
logistic regression model examined effect modifications. While linkage to care
had an overall increase from 2000 to 2016, the odds of linkage were lower among
certain sub-groups including among people in Dushanbe, men, people engaging in
sex work, injection drug users, and older people. Regional differences exist with
linkage to care, occurring least frequently in Dushanbe. While access to care and
quality of care have increased significantly over time, findings suggest that
linkage to care is low, especially in the capital city where many services are
provided. Evaluation focusing on acceptability of HIV services should be
undertaken to understand why certain people do not link with services. Additional
research about the types of barriers to linking with HIV care is needed to
increase linkage to HIV care.
PMID- 29945542
TI - Effect of Propofol on breast Cancer cell, the immune system, and patient outcome.
AB - Breast cancer is the second leading cause of cancer death in women. Surgery is
the first line of treatment for breast cancer. Retrospective clinical studies
suggest that the type of anesthesia administered during oncological surgery may
influence patient outcome. Propofol, the widely used intravenous anesthetic
agent, may lead to better outcomes compared to volatile anesthetics. Here we
review the literature on the effect of propofol in breast cancer cells, the
immune system, pain management, and patient outcomes. Evidence from the study of
breast cancer cell lines suggests that high concentrations of propofol have both
anti-tumor and pro-tumor effects. Propofol and volatile anesthetics have
different effects on the immune system. Propofol has also been shown to reduce
the development and severity of acute and chronic pain following surgery.
Although a retrospective study that included many types of cancer indicated that
propofol increases the long-term survival of patients following surgery, the
evidence for this in breast cancer is weak. It has been shown that Propofol
combined with paravertebral block led to change of serum composition that affects
the breast cancer cell behaviors and natural killer cell activity. Prospective
studies are in progress and will be finished within 5 years. The existing
evidence is not sufficient to warrant changes to current anesthetic management.
Further research is needed to clarify the mechanisms by which propofol affects
cancer cells and the immune system.
PMID- 29945543
TI - Restriction associated DNA-genotyping at multiple spatial scales in Arabidopsis
lyrata reveals signatures of pathogen-mediated selection.
AB - BACKGROUND: Genome scans based on outlier analyses have revolutionized detection
of genes involved in adaptive processes, but reports of some forms of selection,
such as balancing selection, are still limited. It is unclear whether high
throughput genotyping approaches for identification of single nucleotide
polymorphisms have sufficient power to detect modes of selection expected to
result in reduced genetic differentiation among populations. In this study, we
used Arabidopsis lyrata to investigate whether signatures of balancing selection
can be detected based on genomic smoothing of Restriction Associated DNA
sequencing (RAD-seq) data. We compared how different sampling approaches (both
within and between subspecies) and different background levels of polymorphism
(inbreeding or outcrossing populations) affected the ability to detect genomic
regions showing key signatures of balancing selection, specifically elevated
polymorphism, reduced differentiation and shifts towards intermediate allele
frequencies. We then tested whether candidate genes associated with disease
resistance (R-gene analogs) were detected more frequently in these regions
compared to other regions of the genome. RESULTS: We found that genomic regions
showing elevated polymorphism contained a significantly higher density of R-gene
analogs predicted to be under pathogen-mediated selection than regions of non
elevated polymorphism, and that many of these also showed evidence for an
intermediate site-frequency spectrum based on Tajima's D. However, we found few
genomic regions that showed both elevated polymorphism and reduced FST among
populations, despite strong background levels of genetic differentiation among
populations. This suggests either insufficient power to detect the reduced
population structure predicted for genes under balancing selection using sparsely
distributed RAD markers, or that other forms of diversifying selection are more
common for the R-gene analogs tested. CONCLUSIONS: Genome scans based on a small
number of individuals sampled from a wide range of populations were sufficient to
confirm the relative scarcity of signatures of balancing selection across the
genome, but also identified new potential disease resistance candidates within
genomic regions showing signatures of balancing selection that would be strong
candidates for further sequencing efforts.
PMID- 29945544
TI - Heart rate variability in healthy term newborns is related to delivery mode: a
prospective observational study.
AB - BACKGROUND: Early postnatal period is characterized by dramatic adaptation
changes of cardiovascular and respiratory systems in newborns. There is still
insufficient data regarding maturation of autonomic regulatory mechanisms in
neonates early after delivery. Aim of this study was to analyze cardiac autonomic
regulation in newborns within the first few postnatal days in relation to
different modes of delivery using time and spectral heart rate variability
analysis. METHODS: Eutrophic healthy term newborns (n = 46) were divided into
three groups according to the delivery mode: vaginal delivery (VD group; n = 16),
vaginal delivery with epidural analgesia (EDA group; n = 16), and caesarean
section under general anesthesia (CS group; n = 14). Heart rate variability
(HRV), blood pressure (BP), and blood oxygen saturation (SpO2) were measured
within the first two hours after birth and on the third to fourth postnatal day.
HRV parameters were evaluated in the time domain (RR intervals, mean square of
successive differences - MSSD) and frequency domain (total spectral power - TP,
absolute and relative low and high frequency powers). RESULTS: The HRV spectral
analysis showed significantly higher relative power of the high-frequency band
(HF%) in the VD group compared to the CS group early after delivery (p = 0.002).
HRV parameters and BP significantly increased on the third to fourth postnatal
day in all groups (p < 0.05). No significant differences in basic
characteristics, BP and SpO2 were identified between groups during both
measurements. CONCLUSIONS: HRV analysis revealed higher cardiovagal modulation in
spontaneously born newborns without analgesia compared to neonates born by
caesarean section. It could represent a potential pathomechanism that leads to
discrete abnormal neurocardiac regulation associated with higher risk for
worsened postnatal adaptation of cardiovascular system in surgically delivered
neonates.
PMID- 29945545
TI - Mannan oligosaccharide requires functional ETC and TLR for biological radiation
protection to normal cells.
AB - BACKGROUND: Low LET Ionizing radiation is known to alter intracellular redox
balance by inducing free radical generation, which may cause oxidative
modification of various cellular biomolecules. The extent of biomolecule
modifications/ damages and changes in vital processes (viz. cellular homeostasis,
inter-/intra-cellular signaling, mitochondrial physiology/dynamics antioxidant
defence systems) are crucial which in turn determine fate of cells. RESULTS: In
the present study, we expended TLR expressing (normal/ transformed) and TLR null
cells; and we have shown that mannan pretreatment in TLR expressing normal cells
offers survival advantage against lethal doses of ionizing radiation. On the
contrary, mannan pretreatment does not offer any protection against radiation to
TLR null cells, NKE rho degrees cells and transformed cells. In normal cells,
abrupt decrease in mitochondrial membrane potential and endogenous ROS levels
occurs following treatment with mannan. We intend to irradiate mannan-pretreated
cells at a specific stage of perturbed mitochondrial functioning and ROS levels
to comprehend if mannan pretreatment offers any survival advantage against
radiation exposure to cells. Interestingly, pre-irradiation treatment of cells
with mannan activates NFkappaB, p38 and JNK, alters mitochondrial physiology,
increases expression of Cu/ZnSOD and MnSOD, minimizes oxidation of mitochondrial
phospholipids and offers survival advantage in comparison to irradiated group, in
TLR expressing normal cells. CONCLUSION: The study demonstrates that TLR and
mitochondrial ETC functions are inevitable in radio-protective efficacy exhibited
by mannan.
PMID- 29945547
TI - Analysis of differences between total IgG and sum of the IgG subclasses in
children with suspected immunodeficiency - indication of determinants.
AB - BACKGROUND: Deficits in disorders of humoral immunity associated with a deficit
of antibodies are the most common primary immunodeficiency. Total IgG and IgG
subclasses measurements are used to diagnose, differentiate and control in
patients with primary and secondary immunodeficiencies. METHODS: The purpose of
the study was to analyze the structure patients group according to difference
between total IgG and sum of the IgG subclasses and to determine factors
affecting the level of this difference. This study was based on data collected
from 670 children referred to the Department of Clinical Immunology and
Pediatrics in order to diagnose the immune disorders. For all children the level
of the total of immunoglobulins IgG and of the IgG subclasses (IgG1, IgG2, IgG3,
IgG4) were determined. The group of children was divided into subgroups according
to gender, age (under 6 years of age, 6.5-12 years, and 12-18 years), and IgG
abnormality (below the normal range, normal and above the normal range). In the
patients group, the total IgG values were on average higher than sum of the IgG
subclasses. RESULTS: Statistical analysis shown the all parameters under study
(age, gender and IgG abnormality) influence statistically significant on the
discrepancy between the sum of the IgG subclasses and total IgG. Assessment of
IgG and IgG subclasses levels is based on different methods what causes the
discrepancy between the sum of the IgG subclasses and total IgG. CONCLUSIONS:
Standardization in that regard is crucial. In addition, we have shown the
reliability of the results obtained. Despite the determination in two different
laboratories and on different analyzers, as well as the freezing process does not
affect the test results.
PMID- 29945546
TI - Identification of putative regulatory regions and transcription factors
associated with intramuscular fat content traits.
AB - BACKGROUND: Integration of high throughput DNA genotyping and RNA-sequencing data
allows for the identification of genomic regions that control gene expression,
known as expression quantitative trait loci (eQTL), on a whole genome scale.
Intramuscular fat (IMF) content and carcass composition play important roles in
metabolic and physiological processes in mammals because they influence insulin
sensitivity and consequently prevalence of metabolic diseases such as obesity and
type 2 diabetes. However, limited information is available on the genetic
variants and mechanisms associated with IMF deposition in mammals. Thus, our
hypothesis was that eQTL analyses could identify putative regulatory regions and
transcription factors (TFs) associated with intramuscular fat (IMF) content
traits. RESULTS: We performed an integrative eQTL study in skeletal muscle to
identify putative regulatory regions and factors associated with intramuscular
fat content traits. Data obtained from skeletal muscle samples of 192 animals was
used for association analysis between 461,466 SNPs and the transcription level of
11,808 genes. This yielded 1268 cis- and 10,334 trans-eQTLs, among which we
identified nine hotspot regions that each affected the expression of > 119 genes.
These putative regulatory regions overlapped with previously identified QTLs for
IMF content. Three of the hotspots respectively harbored the transcription
factors USF1, EGR4 and RUNX1T1, which are known to play important roles in lipid
metabolism. From co-expression network analysis, we further identified modules
significantly correlated with IMF content and associated with relevant processes
such as fatty acid metabolism, carbohydrate metabolism and lipid metabolism.
CONCLUSION: This study provides novel insights into the link between genotype and
IMF content as evident from the expression level. It thereby identifies genomic
regions of particular importance and associated regulatory factors. These new
findings provide new knowledge about the biological processes associated with
genetic variants and mechanisms associated with IMF deposition in mammals.
PMID- 29945548
TI - Maternal sedentary behavior during pre-pregnancy and early pregnancy and mean
offspring birth size: a cohort study.
AB - BACKGROUND: Sedentary behavior is associated with adverse health outcomes in the
general population. Whether sedentary behavior during pregnancy is associated
with newborn outcomes, such as birth size, is not established, and previous
studies have been inconsistent. While previous research suggests that male and
female fetuses respond differently to maternal behaviors, such as physical
activity, the role of infant sex in sedentary behavior-birth size associations
has not been examined. METHODS: Participants in the Omega study, a cohort in
Washington State (1996-2008), reported leisure time sedentary behavior (non-work
time spent sitting), light intensity physical activity, and moderate/vigorous
leisure time physical activity duration in the year before pregnancy (N = 1373)
and in early pregnancy (N = 1535, mean 15 weeks). Offspring birth size was
abstracted from delivery records. Non-parametric calibration weighting was used
to assign adjustment weight (matching the distribution of sociodemographic and
medical characteristics of the full cohort (N = 4128)) to participants with
available sedentary behavior data. Weighted linear regression models were used to
estimate mean differences in offspring birthweight, head circumference, and
ponderal index (birthweight/length3) associated with leisure time sedentary
behavior. Regression models were run overall and stratified by offspring sex.
Isotemporal substitution modeling was used to determine mean differences in
birthweight associated with replacing sedentary behavior with light or
moderate/vigorous physical activity. RESULTS: On average, women spent 2.3 and 2.6
h/day in leisure time sedentary behavior during pre- and early pregnancy,
respectively. There were no associations of pre-pregnancy leisure time sedentary
behavior with mean birthweight, head circumference, or ponderal index (adjusted
beta = - 12, 95% CI: -28, 4.1; beta = 0.0, 95% CI: -0.04, 0.1; and beta = 0.1,
95% CI: -0.2, 0.4, respectively). Early pregnancy sedentary behavior was not
associated with mean birth size. Associations of sedentary behavior with mean
birth size did not differ by offspring sex. Replacing sedentary time with light
or moderate/vigorous physical activity was not associated with mean birthweight.
CONCLUSIONS: We did not observe associations of maternal sedentary behavior
during pre- or early pregnancy with mean offspring birth size. Pre-pregnancy and
early pregnancy sedentary behavior may have important adverse effects on maternal
health, but our results do not support associations with mean offspring birth
size.
PMID- 29945549
TI - Comparative genome-wide characterization leading to simple sequence repeat marker
development for Nicotiana.
AB - BACKGROUND: Simple sequence repeats (SSRs) are tandem repeats of DNA that have
been used to develop robust genetic markers. These molecular markers are powerful
tools for basic and applied studies such as molecular breeding. In the model
plants in Nicotiana genus e.g. N. benthamiana, a comprehensive assessment of SSR
content has become possible now because several Nicotiana genomes have been
sequenced. We conducted a genome-wide SSR characterization and marker development
across seven Nicotiana genomes. RESULTS: Here, we initially characterized
2,483,032 SSRs (repeat units of 1-10 bp) from seven genomic sequences of
Nicotiana and developed SSR markers using the GMATA(r) software package. Of
investigated repeat units, mono-, di- and tri-nucleotide SSRs account for 98% of
all SSRs in Nicotiana. More complex SSR motifs, although rare, are highly
variable between Nicotiana genomes. A total of 1,224,048 non-redundant Nicotiana
(NIX) markers were developed, of which 99.98% are novel. An efficient and uniform
genotyping protocol for NIX markers was developed and validated. We created a web
based database of NIX marker information including amplicon sizes of alleles in
each genome for downloading and online analysis. CONCLUSIONS: The present work
constitutes the first deep characterization of SSRs in seven genomes of
Nicotiana, and the development of NIX markers for these SSRs. Our online marker
database and an efficient genotyping protocol facilitate the application of these
markers. The NIX markers greatly expand Nicotiana marker resources, thus
providing a useful tool for future research and breeding. We demonstrate a novel
protocol for SSR marker development and utilization at the whole genome scale
that can be applied to any lineage of organisms. The Tobacco Markers & Primers
Database (TMPD) is available at http://biodb.sdau.edu.cn/tmpd/index.html.
PMID- 29945550
TI - Reduced phloem uptake of Myzus persicae on an aphid resistant pepper accession.
AB - BACKGROUND: The green peach aphid (GPA), Myzus persicae, is economically one of
the most threatening pests in pepper cultivation, which not only causes direct
damage but also transmits many viruses. Breeding aphid resistant pepper varieties
is a promising and environmentally friendly method to control aphid populations
in the field and in the greenhouse. Until now, no strong sources of resistance
against the GPA have been identified. Therefore the main aims of this study were
to identify pepper materials with a good level of resistance to GPA and to
elucidate possible resistance mechanisms. RESULTS: We screened 74 pepper
accessions from different geographical areas for resistance to M. persicae. After
four rounds of evaluation we identified one Capsicum baccatum accession
(PB2013071) as highly resistant to M. persicae, while the accessions PB2013062
and PB2012022 showed intermediate resistance. The resistance of PB2013071
resulted in a severely reduced uptake of phloem compared to the susceptible
accession, as determined by Electrical Penetration Graph (EPG) studies. Feeding
of M. persicae induced the expression of callose synthase genes and resulted in
callose deposition in the sieve elements in resistant, but not in susceptible
plants. CONCLUSIONS: Three aphid resistant pepper accessions were identified,
which will be important for breeding aphid resistant pepper varieties in the
future. The most resistant accession PB2013071 showed phloem-based resistance
against aphid infestation.
PMID- 29945551
TI - Improving emergency obstetric care and reversing the underutilisation of vacuum
extraction: a qualitative study of implementation in Tete Province, Mozambique.
AB - BACKGROUND: Maternal and perinatal mortality in Mozambique were declining at a
slow pace, despite progress in coverage of institutional childbirth.
Implementation of quality emergency obstetric care including vacuum extraction
remained inadequate. In 2015-2017, Tete Province achieved remarkable progress in
improving emergency obstetric care and reversing the underutilisation of vacuum
extraction, with encouraging results for maternal and perinatal outcomes, despite
severe resource constraints. This paper presents the experience of Tete Province,
generating a rich, contextualised understanding, which might provide
generalizable insights and lessons. METHODS: This qualitative study design is
used to present Tete's experience in improving emergency obstetric care and
reversing the underutilisation of vacuum extraction, drawing on principles from
implementation science and applying a systems thinking approach. Sources include
routine data, documents, social media messages, and the lived experience of the
authors, all intimately involved in the implementation process during 2014-2017.
Iterative learning and analysis, involving all authors, led to the final
interpretations. RESULTS: Within a context of severe resource constraints, Tete
applied 4 interventions (training, accreditation, audit, monitoring and
evaluation with feedback) to improve the implementation of emergency obstetric
care. Considerable progress was achieved in vacuum extraction and other signal
functions of emergency obstetric care and in the decision-making process for
caesarean sections, contributing to important reductions in the provincial
institutional maternal mortality and stillbirth rates. Facilitating factors
include attributes of the vacuum extraction itself, of the structural and
organisational environments in which it was introduced, of the people involved in
implementation, and of the process through which the implementation was rolled
out. CONCLUSIONS: The lessons from implementation science and systems thinking
can contribute to surprising results in the improvement of emergency obstetric
care including the use of vacuum extraction, even in a severely resource
constrained setting. The creation of conditions for real change, with empowerment
of the staff and managers at the front-line of day-to-day practice in Tete may
inspire others in similar conditions and circumstances. The underutilisation of
vacuum extraction in middle- and low-income countries is indeed a missed
opportunity. Its reversion is possible and provides a good chance to make
considerable difference in maternal and perinatal outcomes.
PMID- 29945553
TI - Genetic diversity analysis of cultivated and wild grapevine (Vitis vinifera L.)
accessions around the Mediterranean basin and Central Asia.
AB - BACKGROUND: The mountainous region between the Caucasus and China is considered
to be the center of domestication for grapevine. Despite the importance of
Central Asia in the history of grape growing, information about the extent and
distribution of grape genetic variation in this region is limited in comparison
to wild and cultivated grapevines from around the Mediterranean basin. The
principal goal of this work was to survey the genetic diversity and relationships
among wild and cultivated grape germplasm from the Caucasus, Central Asia, and
the Mediterranean basin collectively to understand gene flow, possible
domestication events and adaptive introgression. RESULTS: A total of 1378 wild
and cultivated grapevines collected around the Mediterranean basin and from
Central Asia were tested with a set of 20 nuclear SSR markers. Genetic data were
analyzed (Cluster analysis, Principal Coordinate Analysis and STRUCTURE) to
identify groups, and the results were validated by Nei's genetic distance,
pairwise FST analysis and assignment tests. All of these analyses identified
three genetic groups: G1, wild accessions from Croatia, France, Italy and Spain;
G2, wild accessions from Armenia, Azerbaijan and Georgia; and G3, cultivars from
Spain, France, Italy, Georgia, Iran, Pakistan and Turkmenistan, which included a
small group of wild accessions from Georgia and Croatia. Wild accessions from
Georgia clustered with cultivated grape from the same area (proles pontica), but
also with Western Europe (proles occidentalis), supporting Georgia as the ancient
center of grapevine domestication. In addition, cluster analysis indicated that
Western European wild grapes grouped with cultivated grapes from the same area,
suggesting that the cultivated proles occidentalis contributed more to the early
development of wine grapes than the wild vines from Eastern Europe. CONCLUSIONS:
The analysis of genetic relationships among the tested genotypes provided
evidence of genetic relationships between wild and cultivated accessions in the
Mediterranean basin and Central Asia. The genetic structure indicated a
considerable amount of gene flow, which limited the differentiation between the
two subspecies. The results also indicated that grapes with mixed ancestry occur
in the regions where wild grapevines were domesticated.
PMID- 29945552
TI - Identification and characterization of long noncoding RNAs and mRNAs expression
profiles related to postnatal liver maturation of breeder roosters using Ribo
zero RNA sequencing.
AB - BACKGROUND: The liver is mainly hematopoietic in the embryo, and converts into a
major metabolic organ in the adult. Therefore, it is intensively remodeled after
birth to adapt and perform adult functions. Long non-coding RNAs (lncRNAs) are
involved in organ development and cell differentiation, likely they have
potential roles in regulating postnatal liver development. Herein, in order to
understand the roles of lncRNAs in postnatal liver maturation, we analyzed the
lncRNAs and mRNAs expression profiles in immature and mature livers from one-day
old and adult (40 weeks of age) breeder roosters by Ribo-Zero RNA-Sequencing.
RESULTS: Around 21,939 protein-coding genes and 2220 predicted lncRNAs were
expressed in livers of breeder roosters. Compared to protein-coding genes, the
identified chicken lncRNAs shared fewer exons, shorter transcript length, and
significantly lower expression levels. Notably, in comparison between the livers
of newborn and adult breeder roosters, a total of 1570 mRNAs and 214 lncRNAs were
differentially expressed with the criteria of log2fold change > 1 or < - 1 and P
values < 0.05, which were validated by qPCR using randomly selected five mRNAs
and five lncRNAs. Further GO and KEGG analyses have revealed that the
differentially expressed mRNAs were involved in the hepatic metabolic and immune
functional changes, as well as some biological processes and pathways including
cell proliferation, apoptotic and cell cycle that are implicated in the
development of liver. We also investigated the cis- and trans- regulatory effects
of differentially expressed lncRNAs on its target genes. GO and KEGG analyses
indicated that these lncRNAs had their neighbor protein coding genes and trans
regulated genes associated with adapting of adult hepatic functions, as well as
some pathways involved in liver development, such as cell cycle pathway, Notch
signaling pathway, Hedgehog signaling pathway, and Wnt signaling pathway.
CONCLUSIONS: This study provides a catalog of mRNAs and lncRNAs related to
postnatal liver maturation of chicken, and will contribute to a fuller
understanding of biological processes or signaling pathways involved in
significant functional transition during postnatal liver development that
differentially expressed genes and lncRNAs could take part in.
PMID- 29945554
TI - Identification of sonic hedgehog-regulated genes and biological processes in the
cranial neural crest mesenchyme by comparative transcriptomics.
AB - BACKGROUND: The evolutionarily conserved Sonic Hedgehog (Shh) signaling pathway
is essential for embryogenesis and orofacial development. SHH ligand secreted
from the surface ectoderm activates pathway activity in the underlying cranial
neural crest cell (cNCC)-derived mesenchyme of the developing upper lip and
palate. Disruption of Shh signaling causes orofacial clefts, but the biological
action of Shh signaling and the full set of Shh target genes that mediate normal
and abnormal orofacial morphogenesis have not been described. RESULTS: Using
comparative transcriptional profiling, we have defined the Shh-regulated genes of
the cNCC-derived mesenchyme. Enrichment analysis demonstrated that in cultured
cNCCs, Shh-regulated genes are involved in smooth muscle and chondrocyte
differentiation, as well as regulation of the Forkhead family of transcription
factors, G1/S cell cycle transition, and angiogenesis. Next, this gene set from
Shh-activated cNCCs in vitro was compared to the set of genes dysregulated in the
facial primordia in vivo during the initial pathogenesis of Shh pathway inhibitor
induced orofacial clefting. Functional gene annotation enrichment analysis of the
112 Shh-regulated genes with concordant expression changes linked Shh signaling
to interdependent and unique biological processes including mesenchyme
development, cell adhesion, cell proliferation, cell migration, angiogenesis,
perivascular cell markers, and orofacial clefting. CONCLUSIONS: We defined the
Shh-regulated transcriptome of the cNCC-derived mesenchyme by comparing the
expression signatures of Shh-activated cNCCs in vitro to primordial midfacial
tissues exposed to the Shh pathway inhibitor in vivo. In addition to improving
our understanding of cNCC biology by determining the identity and possible roles
of cNCC-specific Shh target genes, this study presents novel candidate genes
whose examination in the context of human orofacial clefting etiology is
warranted.
PMID- 29945555
TI - Remote ischemic preconditioning for cardioprotection in elective inpatient
abdominal surgery - a randomized controlled trial.
AB - BACKGROUND: Perioperative myocardial injury (PMI) is common in elective inpatient
abdominal surgery and correlates with mortality risk. Simple measures for
reducing PMI in this cohort are needed. This study evaluated whether remote
ischemic preconditioning (RIPC) could reduce PMI in elective inpatient abdominal
surgery. METHODS: This was a double-blind, sham-controlled trial with 1:1
parallel randomization. PMI was defined as any post-operative serum troponin T
(hs-TNT) > 14 ng/L. Eighty-four participants were randomized to receiving RIPC (5
min of upper arm ischemia followed by 5 min reperfusion, for three cycles) or a
sham-treatment immediately prior to surgery. The primary outcome was mean peak
post-operative troponin in patients with PMI, and secondary outcomes included
mean hs-TnT at individual timepoints, post-operative hs-TnT area under the curve
(AUC), cardiovascular events and mortality. Predictors of PMI were also
collected. Follow up was to 1 year. RESULTS: PMI was observed in 21% of
participants. RIPC did not significantly influence the mean peak post-operative
hs-TnT concentration in these patients (RIPC 25.65 ng/L [SD 9.33], sham-RIPC
23.91 [SD 13.2], mean difference 1.73 ng/L, 95% confidence interval - 9.7 to 13.1
ng/L, P = 0.753). The treatment did not influence any secondary outcome with the
pre-determined definition of PMI. Redefining PMI as > 5 ng/L in line with recent
data revealed a non-significant lower incidence in the RIPC cohort (68% vs 81%, P
= 0.211), and significantly lower early hs-TnT release (12 h time-point, RIPC 5.5
ng/L [SD 5.5] vs sham 9.1 ng/L [SD 8.2], P = 0.03). CONCLUSIONS: RIPC did not at
reduce the incidence or severity of PMI in these general surgical patients using
pre-determined definitions. PMI is nonetheless common and effective
cardioprotective strategies are required. TRIAL REGISTRATION: This trial was
registered with Clinicaltrials.gov, NCT01850927 , 5th July 2013.
PMID- 29945556
TI - Obstetric fistula policy in Nigeria: a critical discourse analysis.
AB - BACKGROUND: In 2012, Nigeria's Federal Ministry of Health published its National
Strategic Framework for the Elimination of Obstetric Fistula (NSFEOF), 2011-2015.
The framework has since lapsed and there is no tangible evidence that the goal of
eliminating obstetric fistula was met. To further inform future policy directions
on obstetric fistula in Nigeria, this paper explores how the NSFEOF
conceptualized obstetric fistula and its related issues, including child marriage
and early childbearing. METHODS: A critical discourse analysis of the policy was
performed. We examined four policies in addition to the strategic framework: the
Nigerian constitution; the Marriage Act; the Matrimonial Causes Act; and the
National Reproductive Health Policy. We used the three phases of critical
discourse analysis: textual analysis, analysis of discourse practice, and
analysis of discursive events as instances of sociocultural practice. RESULTS:
The analysis demonstrates that, despite its title, the policy document focuses on
reduction rather than elimination of obstetric fistula. The overall orientation
of the policy is downstream, with minimal focus on prevention. The policy
language suggests victim blaming. Furthermore, the extent to which subnational
stakeholders in government and civil society were engaged in decision-making
process for developing this policy is ambiguous. Although the policy is
ostensibly based on principles of social justice and equity, several rhetorical
positions suggest that the Nigerian constitutional environment and justice
systems make no real provisions to protect the reproductive rights of girls in
accordance with the United Nations' "2030 Agenda for Sustainable Development."
CONCLUSION: This analysis establishes that the Nigerian constitution, justice
environment and the obstetric fistula policy itself do not demonstrate clear
commitment to eradicating obstetric fistula. Specifically, a clear commitment to
eradicating obstetric fistula would see the constitution and Marriage Act of
Nigeria specify an age of consent that is consistent with the agenda to prevent
obstetric fistula. Additionally, a policy to end obstetric fistulas in Nigeria
must purposefully address the factors creating barrier to women's access to
quality maternal healthcare services. Future policies and programs to eliminate
obstetric fistulas should include perspectives of nurses, midwives, researchers
and, women's interest groups.
PMID- 29945557
TI - The relationship between maternal anxiety and cortisol during pregnancy and birth
weight of chinese neonates.
AB - BACKGROUND: To determine the relationship between maternal anxiety and cortisol
values and birth weight at various stages of pregnancy. METHODS: Two hundred
sixteen pregnant Chinese women were assessed for anxiety and depression and had
measurement of morning fasting serum cortisol. Women were assessed either in the
first (71), second (72) or third (73) trimester. Birth weights of all children
were recorded. RESULTS: There were significant negative correlations between
anxiety level and birth weight of - 0.507 (p < 0.01) and - 0.275 (p < 0.05) in
trimesters 1and 2. In trimester 3 the negative relation between anxiety and birth
weight of -.209 failed to reach significance (p = 0.070). There was no relation
between depression and birth weight in any trimester (p > 0.5 for all). Maternal
cortisol was significantly inversely related to birth weight in trimester 1 (r =
0.322) and with borderline significance in trimester 2 (r = - 0.229). Anxiety
score and maternal cortisol were significantly correlated in each trimester (r =
0.551, 0.650, 0.537). When both anxiety score and maternal cortisol were
simultaneously included in multiple regression analyses only anxiety score
remained significant. CONCLUSION: Whilst both maternal anxiety score and maternal
cortisol are inversely related to birth weight the associations with anxiety
score were more robust perhaps indicating the importance of mechanisms other
than, or in addition to, maternal cortisol in mediating the effects of anxiety.
The findings indicate the importance of measures to reduce maternal anxiety,
particularly of a severe degree, at all stages of pregnancy. TRIAL REGISTRATION:
The study was approved by the Ethics Committee of the 1st Affiliated Hospital of
Xi'an Jiaotong University.
PMID- 29945558
TI - Frequency of intra-abdominal organ injury is higher in patients with concomitant
stab wounds to other anatomical areas.
AB - BACKGROUND: Management of stable patients with abdominal stab wound remains
controversial, particularly for those with no clear indications for explorative
laparotomy. We evaluated the risk of intra-abdominal injury in stab wound victims
concomitantly stabbed in other anatomical body areas. METHODS: We performed a
retrospective cohort study of patients with abdominal stab wounds recorded in the
Israeli National Trauma Registry from January 1st, 1997, to December 31st, 2013.
Patients with an isolated abdominal stab wound were compared to those with
concomitant stab wounds to other anatomical areas. Intra-abdominal organ injury
was defined by imaging or surgery findings. Multivariate analysis using a
logistic regression model was conducted to assess independent risk for intra
abdominal organ injury. RESULTS: The study included 3964 patients. After
controlling for age, gender and hypotension on arrival, patients with multi
regional stab wounds had an increased risk of intra-abdominal injury (OR = 1.3,
CI 95% 1.1-1.6, p < 0.001). These patients also had a higher rate of injury to
the solid organs than patients with an isolated abdominal stab wound.
CONCLUSIONS: Patients with multi-regional stab wounds have an increased risk of
intra-abdominal injury. Worldwide accepted "clinical follow up" protocol may not
be appropriate in management of patients with multi-regional stab wounds.
PMID- 29945559
TI - GenoGAM 2.0: scalable and efficient implementation of genome-wide generalized
additive models for gigabase-scale genomes.
AB - BACKGROUND: GenoGAM (Genome-wide generalized additive models) is a powerful
statistical modeling tool for the analysis of ChIP-Seq data with flexible
factorial design experiments. However large runtime and memory requirements of
its current implementation prohibit its application to gigabase-scale genomes
such as mammalian genomes. RESULTS: Here we present GenoGAM 2.0, a scalable and
efficient implementation that is 2 to 3 orders of magnitude faster than the
previous version. This is achieved by exploiting the sparsity of the model using
the SuperLU direct solver for parameter fitting, and sparse Cholesky
factorization together with the sparse inverse subset algorithm for computing
standard errors. Furthermore the HDF5 library is employed to store data
efficiently on hard drive, reducing memory footprint while keeping I/O low. Whole
genome fits for human ChIP-seq datasets (ca. 300 million parameters) could be
obtained in less than 9 hours on a standard 60-core server. GenoGAM 2.0 is
implemented as an open source R package and currently available on GitHub. A
Bioconductor release of the new version is in preparation. CONCLUSIONS: We have
vastly improved the performance of the GenoGAM framework, opening up its
application to all types of organisms. Moreover, our algorithmic improvements for
fitting large GAMs could be of interest to the statistical community beyond the
genomics field.
PMID- 29945560
TI - Evaluating inner retinal dimples after inner limiting membrane removal using
multimodal imaging of optical coherence tomography.
AB - BACKGROUND: To evaluate inner retinal dimples after peeling of the inner limiting
membrane (ILM) for macular holes (lamellar macular hole [LMH] and full-thickness
macular hole [FTMH]) via multiple imaging modes of spectral-domain optical
coherence tomography (OCT) and to assess their relationship with preoperative
vitreoretinal interface conditions. METHODS: The data of 38 eyes in 35 patients
who underwent surgery for LMH, and FTMH were retrospectively studied. The
presence of postoperative inner retinal dimples was judged by a combination of en
face OCT layer images and cross-sectional images. The demographic and clinical
characteristics of eyes with and without inner retinal defects were compared to
identify factors involved in the formation of the defects. RESULTS: Inner retinal
defects were found in 26 eyes (68%) after surgery. They appeared on the en face
OCT ILM layer images as multiple dark spots limited to the ILM peeling area, and
corresponded to dimples or pitting of inner retinal layers on cross-sectional OCT
images. In 5 cases (19%), apparent progression of inner retinal defects was
observed on the en face OCT images as increasing numbers and sizes of the dark
spots, which seemed to follow an eccentric growth pattern starting from the
central macula. In addition, highly myopic eyes were found to be associated with
the formation of more severe inner retinal defects. CONCLUSIONS: Multiple imaging
modes of en face spectral-domain OCT provide comprehensive information about the
appearance of inner retinal dimples. High myopic eyes seem to develop more severe
inner retinal defects after ILM peeling.
PMID- 29945561
TI - Nausea and vomiting during pregnancy associated with lower incidence of preterm
births: the Japan Environment and Children's Study (JECS).
AB - BACKGROUND: Nausea and vomiting during pregnancy (NVP) is considered to be
associated with favorable fetal outcomes, such as a decreased risk for
spontaneous abortion. However, the relationship between NVP and preterm births
remains unknown. This study was conducted to evaluate the association between NVP
and the risk of preterm births. METHODS: The dataset of a birth cohort study, the
Japan Environment and Children's Study (JECS), was retrospectively reviewed.
Participants' experience of NVP prior to 12 gestational weeks were evaluated by a
questionnaire administered from 22 weeks of pregnancy to 1 month before delivery.
NVP responses were elicited against four choices based on which the study
population was divided into four subcohorts. Preterm birth was the main study
outcome. Logistic regression analysis was used to quantify an association between
NVP and risk of preterm birth. RESULTS: Of 96,056 women, 79,460 (82.7%)
experienced some symptoms of NVP and 10,518 (10.9%) experienced severe NVP.
Compared to those who did not experience NVP, women with severe NVP had lower
odds for preterm birth [adjusted odds ratio (aOR) 0.84, 95% confidence interval
(95% CI) 0.74-0.95]. An even lower OR was found among very preterm birth and
extremely preterm birth (aOR 0.44, 95% CI 0.29-0.65). CONCLUSION: An inverse
association exists between NVP and preterm births, especially, very preterm
births and extremely preterm births.
PMID- 29945562
TI - Nanoliposomal irinotecan with fluorouracil for the treatment of advanced
pancreatic cancer, a single institution experience.
AB - BACKGROUND: Effective treatment options for advanced pancreatic cancer are
finite. NAPOLI-1, a phase III randomized trial, demonstrated the efficacy of
nanoliposomal irinotecan with fluorouracil/leucovorin (nal-IRI + 5-FU/LV) for the
treatment of advanced pancreatic cancer following progression on gemcitabine
based chemotherapy. There are limited additional data on the safety and efficacy
of nal-IRI + 5-FU/LV following FDA approval in October 2015. We examined the post
approval safety and effectiveness of nal-IRI + 5-FU/LV in advanced pancreatic
cancer patients receiving treatment at Memorial Sloan Kettering Cancer Center.
METHODS: A retrospective chart review was conducted of all patients beginning
treatment with nal-IRI + 5-FU/LV from October 2015 through June 2017. Using the
electronic medical record and institutional database, information was extracted
pertaining to demographics, performance status (ECOG), prior therapies, dose,
duration of treatment, adverse events, progression free survival (PFS), overall
survival (OS) and treatment response. RESULTS: Fifty six patients were
identified. Median progression free survival (PFS) was 2.9 months and median
overall survival (OS) was 5.3 months. Patients with prior disease progression on
irinotecan experienced PFS and OS of 2.2 and 3.9 mo, respectively. Patients
without prior irinotecan exposure experienced significantly longer PFS (4.8 mo, p
= 0.02) and OS (7.7 mo, p = 0.002), as did patients who received prior irinotecan
without disease progression (PFS, 5.7 mo, p = 0.04; OS, 9.0 mo, p = .04).
Progression on prior irinotecan was associated with greater lines of prior
advanced disease chemotherapy (2 vs 1). Dose reductions (DR) were most frequently
due to fatigue (42%) and diarrhea (37%), but were not associated with worse
outcomes. In fact, patients with >=1 DR experienced longer PFS (5.4 v 2.6 mo, p =
0.035). Sequential therapy with nab-paclitaxel + gemcitabine (nab-P + Gem)
followed by nal-IRI + 5-FU/LV (n = 25) resulted in OS of 23.0 mo. Mutations in
TP53 were associated with shorter PFS. CONCLUSIONS: These data support the safety
and efficacy of nal-IRI + 5-FU/LV, reinforcing results of NAPOLI-1. Patients
without disease progression on prior irinotecan fared significantly better than
patients with progression, when treated with nal-IRI + 5-FU/LV. Sequential
therapy with nab-P + Gem followed by nal-IRI + 5-FU/LV demonstrates encouraging
median OS. These findings provide guidance for patients most likely to benefit
from nal-IRI + 5-FU/LV.
PMID- 29945563
TI - Estimates and predictors of health care costs of esophageal adenocarcinoma: a
population-based cohort study.
AB - BACKGROUND: Esophageal adenocarcinoma (EAC) incidence is increasing rapidly.
Esophageal cancer has the second lowest 5-year survival rate of people diagnosed
with cancer in Canada. Given the poor survival and the potential for further
increases in incidence, phase-specific cost estimates constitute an important
input for economic evaluation of prevention, screening, and treatment
interventions. The study aims to estimate phase-specific net direct medical costs
of care attributable to EAC, costs stratified by cancer stage and treatment, and
predictors of total net costs of care for EAC. METHODS: A population-based
retrospective cohort study was conducted using Ontario Cancer Registry-linked
administrative health data from 2003 to 2011. The mean net costs of EAC care per
30 patient-days (2016 CAD) were estimated from the payer perspective using phase
of care approach and generalized estimating equations. Predictors of net cost by
phase of care were based on a generalized estimating equations model with a
logarithmic link and gamma distribution adjusting for sociodemographic and
clinical factors. RESULTS: The mean net costs of EAC care per 30 patient-days
were $1016 (95% CI, $955-$1078) in the initial phase, $669 (95% CI, $594-$743) in
the continuing care phase, and $8678 (95% CI, $8217-$9139) in the terminal phase.
Overall, stage IV at diagnosis and surgery plus radiotherapy for EAC incurred the
highest cost, particularly in the terminal phase. Strong predictors of higher net
costs were receipt of chemotherapy plus radiotherapy, surgery plus chemotherapy,
radiotherapy alone, surgery alone, and chemotherapy alone in the initial and
continuing care phases, stage III-IV disease and patients diagnosed with EAC
later in a calendar year (2007-2011) in the initial and terminal phases,
comorbidity in the continuing care phase, and older age at diagnosis (70-74
years), and geographic region in the terminal phase. CONCLUSIONS: Costs of care
vary by phase of care, stage at diagnosis, and type of treatment for EAC. These
cost estimates provide information to guide future resource allocation decisions,
and clinical and policy interventions to reduce the burden of EAC.
PMID- 29945564
TI - End-of-life decisions and practices for very preterm infants in the Wallonia
Brussels Federation of Belgium.
AB - BACKGROUND: Very preterm birth (24 to < 32 week's gestation) is a major public
health issue due to its prevalence, the clinical and ethical questions it raises
and the associated costs. It raises two major clinical and ethical dilemma: (i)
during the perinatal period, whether or not to actively manage a baby born very
prematurely and (ii) during the postnatal period, whether or not to continue a
curative treatment plan initiated at birth. The Wallonia-Brussels Federation in
Belgium counts 11 neonatal intensive care units. METHODS: An inventory of key
practices was compiled on the basis of an online questionnaire that was sent to
the 65 neonatologists working in these units. The questionnaire investigated care
related decisions and practices during the antenatal, perinatal and postnatal
periods, as well as personal opinions on the possibility of standardising and/or
legislating for end-of-life decisions and practices. The participation rate was
89% (n = 58). RESULTS: The results show a high level of homogeneity pointing to
overall agreement on the main principles governing curative practice and the
gestational age that can be actively managed given the current state of
knowledge. There was, however, greater diversity regarding principles governing
the transition to end-of-life care, as well as opinions about the need for a
common protocol or law to govern such practices. CONCLUSION: Our results reflect
the uncertainty inherent in the complex and diverse situations that are
encountered in this extreme area of clinical practice, and call for qualitative
research and expert debates to further document and make recommendations for best
practices regarding several "gray zones" of end-of-life care in neonatology, so
that high quality palliative care may be granted to all neonates concerned with
end-of-life decisions.
PMID- 29945566
TI - Childhood adversity and parent perceptions of child resilience.
AB - BACKGROUND: Adverse childhood experiences (ACEs) negatively impact health
throughout the life course. For children exposed to ACEs, resilience may be
particularly important. However, the literature regarding resilience,
particularly the self-regulation aspect of resilience, is not often described in
children with ACEs. Additionally, family and community factors that might help
promote resilience in childhood may be further elucidated. We aimed to describe
the relationship between ACEs and parent-perceived resilience in children and
examine the child, family, and community-level factors associated with child
resilience. METHODS: Using the US-based, 2011-2012 National Survey of Children's
Health, we examined adverse childhood experiences (NSCH-ACEs) as the main
exposure. Affirmative answers to adverse experiences generated a total parent
reported NSCH-ACE score. Bivariate and multivariable logistic regression models
were constructed for parent-perceived child resilience and its association with
ACEs, controlling for child, family, and neighborhood-level factors. RESULTS:
Among 62,200 US children 6-17 years old, 47% had 0 ACEs, 26% had 1 ACE, 19% had 2
3 ACEs, and 8% had 4 or more ACEs. Child resilience was associated with ACEs in a
dose-dependent relationship: as ACEs increased, the probability of resilience
decreased. This relationship persisted after controlling for child, family, and
community factors. Specific community factors, such as neighborhood safety (p <
.001), neighborhood amenities (e.g., libraries, parks) (p < .01) and mentorship
(p < .05), were associated with significantly higher adjusted probabilities of
resilience, when compared to peers without these specific community factors.
CONCLUSIONS: While ACEs are common and may be difficult to prevent, there may be
opportunities for health care providers, child welfare professionals, and
policymakers to strengthen children and families by supporting community-based
activities, programs, and policies that promote resilience in vulnerable children
and communities in which they live.
PMID- 29945565
TI - MicroRNAs as markers of progression in cervical cancer: a systematic review.
AB - BACKGROUND: Invasive cervical cancer (ICC) is caused by high-risk human
papillomavirus types (HR-HPVs) and is usually preceded by a long phase of
intraepithelial neoplasia (CIN). Before invasion, (epi) genetic changes,
potentially applicable as molecular markers within cervical screening, occur in
HPV host cells. Epigenetic alterations, such as dysregulation of microRNA (miRNA)
expression, are frequently observed in ICC. The mechanisms and role of miRNA
dysregulation in cervical carcinogenesis are still largely unknown. METHODS: We
provide an overview of the studies investigating miRNA expression in relation to
ICC progression, highlighting their common outcomes and their
weaknesses/strengths. To achieve this, we systematically searched through Pubmed
database all articles between January 2010 and December 2017. RESULTS: From the
24 studies retrieved, miR-29a and miR-21 are the most frequently down- and up
regulated in ICC progression, respectively. Microarray-based studies show a small
overlap, with miR-10a, miR-20b, miR-9, miR-16 and miR-106 found repeatedly
dysregulated. miR-34a, miR-125 and miR-375 were also found dysregulated in
cervical exfoliated cells in relation to cancer progression. CONCLUSIONS: The
pivotal role of miRNAs in ICC progression and initial development is becoming
more and more relevant. Available studies are essentially based on convenience
material, entailing possible selection bias, and frequently of small size: all
these points still represent a limitation to a wide comprehension of miRNAs
relevant for ICC. The targeted approach instead of a genome-wide investigation
still precludes the identification of all the relevant miRNAs in the process. The
implementation of deep sequencing on large scale population-based studies will
help to discover and validate the relation between altered miRNA expression and
CC progression for the identification of biomarkers. Optimally, once explored on
a miRNome scale, small specific miRNA signatures maybe used in the context of
screening.
PMID- 29945567
TI - Pancreatic cancer as a sentinel for hereditary cancer predisposition.
AB - BACKGROUND: Genes associated with hereditary breast and ovarian cancer (HBOC) and
colorectal cancer (CRC) predisposition have been shown to play a role in
pancreatic cancer susceptibility. Growing evidence suggests that pancreatic
cancer may be useful as a sentinel cancer to identify families that could benefit
from HBOC or CRC surveillance, but to date pancreatic cancer is only considered
an indication for genetic testing in the context of additional family history.
METHODS: Preliminary data generated at the Huntsman Cancer Hospital (HCH)
included variants identified on a custom 34-gene panel or 59-gene panel including
both known HBOC and CRC genes for respective sets of 66 and 147 pancreatic cancer
cases, unselected for family history. Given the strength of preliminary data and
corresponding literature, 61 sequential pancreatic cancer cases underwent a
custom 14-gene clinical panel. Sequencing data from HCH pancreatic cancer cases,
pancreatic cancer cases of the Cancer Genome Atlas (TCGA), and an unselected
pancreatic cancer screen from the Mayo Clinic were combined in a meta-analysis to
estimate the proportion of carriers with pathogenic and high probability of
pathogenic variants of uncertain significance (HiP-VUS). RESULTS: Approximately
8.6% of unselected pancreatic cancer cases at the HCH carried a variant with
potential HBOC or CRC screening recommendations. A meta-analysis of unselected
pancreatic cancer cases revealed that approximately 11.5% carry a pathogenic
variant or HiP-VUS. CONCLUSION: With the inclusion of both HBOC and CRC
susceptibility genes in a panel test, unselected pancreatic cancer cases act as a
useful sentinel cancer to identify asymptomatic at-risk relatives who could
benefit from relevant HBOC and CRC surveillance measures.
PMID- 29945568
TI - Acetylcholinesterase inhibitor insecticides related acute poisoning, availability
and sales: trends during the post-insecticide-ban period of Anuradhapura, Sri
Lanka.
AB - BACKGROUND: Acetylcholinesterase inhibitor insecticides (AChEIIs) were used
extensively in the agrarian region of Anuradhapura for the past few decades. As a
result, the region faced a heightened risk of toxicity. Carbaryl, carbofuran,
chlorpyrifos, dimethoate, and fenthion were the five hazardous AChEIIs banned
from Anuradhapura in 2014. Assessment of post-ban trends in acute poisoning will
reveal the impact of the ban. Data on availability and sales of remaining AChEIIs
will guide towards preventive measures against related toxicities. METHODS: Cross
sectional surveys were conducted at Anuradhapura district of Sri Lanka. Details
related to acute AChEII poisoning were sorted from the Teaching Hospital
Anuradhapura. Main insecticide vendors in Anuradhapura were surveyed to find
information on availability and sales of AChEIIs. Chi-square for goodness of fit
was performed for trends in acute poisoning and sales. RESULTS: Hospital
admissions related to acute AChEII poisoning have declined from 554 in 2013 to
272 in 2017. Deaths related to acute AChEII poisoning have declined from 27 in
2013 to 13 in 2017. Sales of all five banned AChEIIs had reduced by 100%. Sales
of the remaining AChEIIs were declining, except for acephate, phenthoate, and
profenofos. However, one of the top selling, most frequently abused carbosulfan,
had the highest risk of toxicity. Chi-square for goodness of fit showed a
significance (P < 0.001) between the trends of hospital admissions for acute
AChEII poisoning and the sales related to AChEIIs. CONCLUSIONS: Hospital
admissions related to acute poisoning was declining along with the overall sales
of remaining AChEIIs, during the post-AChEII ban period. Nevertheless, future
vigilance is needed on the remaining AChEIIs to predict and prevent related
toxicities.
PMID- 29945569
TI - Use of a novel electronic maternal surveillance system to generate automated
alerts on the labor and delivery unit.
AB - BACKGROUND: Maternal early warning systems reduce maternal morbidity. We
developed an electronic maternal surveillance system capable of visually
summarizing the labor and delivery census and identifying changes in clinical
status. Automatic page alerts to clinical providers, using an algorithm developed
at our institution, were incorporated in an effort to improve early detection of
maternal morbidity. We report the frequency of pages generated by the system. To
our knowledge, this is the first time such a system has been used in peripartum
care. METHODS: Alert criteria were developed after review of maternal early
warning systems, including the Maternal Early Warning Criteria (MEWC). Careful
consideration was given to the frequency of pages generated by the surveillance
system. MEWC notification criteria were liberalized and a paging algorithm was
created that triggered paging alerts to first responders (nurses) and then
managing services due to the assumption that paging all clinicians for each vital
sign triggering MEWC would generate an inordinate number of pages. For
preliminary analysis, to determine the effect of our automated paging algorithm
on alerting frequency, the paging frequency of this system was compared to the
frequency of vital signs meeting the Maternal Early Warning Criteria (MEWC). This
retrospective analysis was limited to a sample of 34 patient rooms uniquely
capable of storing every vital sign reported by the bedside monitor. RESULTS:
Over a 91-day period, from April 1 to July 1, 2017, surveillance was conducted
from 64 monitored beds, and the obstetrics service received one automated page
every 2.3 h. The most common triggers for alerts were for hypertension and
tachycardia. For the subset of 34 patient rooms uniquely capable of real-time
recording, one vital sign met the MEWC every 9.6 to 10.3 min. Anecdotally, the
system was well-received. CONCLUSIONS: This novel electronic maternal
surveillance system is designed to reduce cognitive bias and improve timely
clinical recognition of maternal deterioration. The automated paging algorithm
developed for this software dramatically reduces paging frequency compared to
paging for isolated vital sign abnormalities alone. Long-term, prospective
studies will be required to determine its impact on patient outcomes.
PMID- 29945570
TI - PanACEA: a bioinformatics tool for the exploration and visualization of bacterial
pan-chromosomes.
AB - BACKGROUND: Bacterial pan-genomes, comprised of conserved and variable genes
across multiple sequenced bacterial genomes, allow for identification of genomic
regions that are phylogenetically discriminating or functionally important. Pan
genomes consist of large amounts of data, which can restrict researchers ability
to locate and analyze these regions. Multiple software packages are available to
visualize pan-genomes, but currently their ability to address these concerns are
limited by using only pre-computed data sets, prioritizing core over variable
gene clusters, or by not accounting for pan-chromosome positioning in the viewer.
RESULTS: We introduce PanACEA (Pan-genome Atlas with Chromosome Explorer and
Analyzer), which utilizes locally-computed interactive web-pages to view ordered
pan-genome data. It consists of multi-tiered, hierarchical display pages that
extend from pan-chromosomes to both core and variable regions to single genes.
Regions and genes are functionally annotated to allow for rapid searching and
visual identification of regions of interest with the option that user-supplied
genomic phylogenies and metadata can be incorporated. PanACEA's memory and time
requirements are within the capacities of standard laptops. The capability of
PanACEA as a research tool is demonstrated by highlighting a variable region
important in differentiating strains of Enterobacter hormaechei. CONCLUSIONS:
PanACEA can rapidly translate the results of pan-chromosome programs into an
intuitive and interactive visual representation. It will empower researchers to
visually explore and identify regions of the pan-chromosome that are most
biologically interesting, and to obtain publication quality images of these
regions.
PMID- 29945571
TI - Estimation of delay to diagnosis and incidence in HIV using indirect evidence of
infection dates.
AB - BACKGROUND: Minimisation of the delay to diagnosis is critical to achieving
optimal outcomes for HIV patients and to limiting the potential for further
onward infections. However, investigation of diagnosis delay is hampered by the
fact that in most newly diagnosed patients the exact timing of infection cannot
be determined and so inferences must be drawn from biomarker data. METHODS: We
develop a Bayesian statistical model to evaluate delay-to-diagnosis distributions
in HIV patients without known infection date, based on viral sequence genetic
diversity and longitudinal viral load and CD4 count data. The delay to diagnosis
is treated as a random variable for each patient and their biomarker data are
modelled relative to the true time elapsed since infection, with this dependence
used to obtain a posterior distribution for the delay to diagnosis. Data from a
national seroconverter cohort with infection date known to within +/- 6 months,
linked to a database of viral sequences, are used to calibrate the model
parameters. An exponential survival model is implemented that allows general
inferences regarding diagnosis delay and pooling of information across groups of
patients. If diagnoses are only observed within a given window period, then it is
necessary to also model incidence as a function of time; we suggest a pragmatic
approach to this problem when dealing with data from an established epidemic. The
model developed is used to investigate delay-to-diagnosis distributions in men
who have sex with men diagnosed with HIV in London in the period 2009-2013 with
unknown date of infection. RESULTS: Cross-validation and simulation analyses
indicate that the models developed provide more accurate information regarding
the timing of infection than does CD4 count-based estimation. Delay-to-diagnosis
distributions were estimated in the London cohort, and substantial differences
were observed according to ethnicity. CONCLUSION: The combination of all
available biomarker data with pooled estimation of the distribution of diagnosis
delays allows for more precise prediction of the true timing of infection in
individual patients, and the models developed also provide useful population
level information.
PMID- 29945572
TI - The Murakami Cohort Study of vitamin D for the prevention of musculoskeletal and
other age-related diseases: a study protocol.
AB - BACKGROUND: Age-related musculoskeletal diseases are becoming increasingly
burdensome in terms of both individual quality of life and medical cost. We
intended to establish a large population-based cohort study to determine
environmental, lifestyle, and genetic risk factors of musculoskeletal and other
age-related diseases, and to clarify the association between vitamin D status and
such diseases. METHODS: We targeted 34,802 residents aged 40-74 years living in
areas of northern Niigata Prefecture, including Sekikawa Village, Awashimaura
Village, and Murakami City (Murakami region). The baseline questionnaire survey,
conducted between 2011 and 2013, queried respondents on their lifestyle and
environmental factors (predictors), and self-reported outcomes. Plasma 25
hydroxyvitamin D (25[OH]D) concentration, an indicator of vitamin D status, was
determined with the Liaison(r) 25OH Vitamin D Total Assay. The primary outcome of
this study was osteoporotic fracture; other outcomes included age-related
diseases including knee osteoarthritis, perception of chronic pain, dementia, and
long-term care insurance use. Mean ages of men and women were 59.2 (SD = 9.3, N =
6907) and 59.0 (SD = 9.3, N = 7457) years, respectively. From the blood samples
provided by 3710 men and 4787 women, mean 25(OH)D concentrations were 56.5 (SD =
18.4) nmol/L (22.6 ng/mL) and 45.4 (SD = 16.5) nmol/L (18.2 ng/mL), respectively.
DISCUSSION: Follow-up surveys are planned every 5 years for 15 years, and
incident cases of our targeted diseases will be followed at hospitals and clinics
in and nearby the cohort area. We anticipate that we will be able to clarify the
association between vitamin D status and multiple disease outcomes in a Japanese
population.
PMID- 29945574
TI - A prospective evaluation of a largely cementless total knee arthroplasty cohort
without patellar resurfacing: 10-year outcomes and survivorship.
AB - BACKGROUND: The theoretical benefits of a mobile bearing design in Total Knee
Arthroplasty (TKA) include increased articular surface conformity with a
reduction in both polyethylene wear and implant interface shear. However, to date
these theoretical advantages have not been translated into published evidence of
superior survivorship. This paper presents the results of a prospective, non
comparative study evaluating the performance of the mobile bearing Low Contact
Stress LCS Complete Rotating Platform TKA in a largely cementless cohort without
patellar resurfacing. METHODS: 237 consecutive patients (240 knees) undergoing
primary TKA were prospectively recruited. All received the LCS Complete Rotating
Platform TKA (DePuy International, Leeds, UK). Clinical and radiographic
assessments were performed at 3, 12, 60 and 120 months post-operatively.
Radiographic evaluation was performed by an independent external surgeon.
RESULTS: The mean age was 70.3 years. 77.5% of cases were cementless.
Radiographic assessment suggested excellent femoral component fixation. 22 tibial
radiolucent lines (RLLs) > 1 mm were observed in 12 knees. No RLLs were
progressive. There have been two revisions; one for late infection and one for
aseptic loosening. No patients underwent secondary patellar resurfacing. The
cumulative implant survivorship, using component revision for any reason as the
endpoint, was 98.9% (95% CI, 95.6 to 99.7%) at 10 years. CONCLUSIONS: The
excellent survivorship at a minimum 10-year follow-up supports the use of
uncemented porous coated fixation without patellar resurfacing with the non
posterior stabilized LCS Complete Rotating Platform TKA.
PMID- 29945573
TI - Gene promoter and exon DNA methylation changes in colon cancer development - mRNA
expression and tumor mutation alterations.
AB - BACKGROUND: DNA mutations occur randomly and sporadically in growth-related
genes, mostly on cytosines. Demethylation of cytosines may lead to genetic
instability through spontaneous deamination. Aims were whole genome methylation
and targeted mutation analysis of colorectal cancer (CRC)-related genes and mRNA
expression analysis of TP53 pathway genes. METHODS: Long interspersed nuclear
element-1 (LINE-1) BS-PCR followed by pyrosequencing was performed for the
estimation of global DNA metlyation levels along the colorectal normal-adenoma
carcinoma sequence. Methyl capture sequencing was done on 6 normal adjacent
(NAT), 15 adenomatous (AD) and 9 CRC tissues. Overall quantitative methylation
analysis, selection of top hyper/hypomethylated genes, methylation analysis on
mutation regions and TP53 pathway gene promoters were performed. Mutations of 12
CRC-related genes (APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, NRAS, MSH6, PIK3CA,
SMAD2, SMAD4, TP53) were evaluated. mRNA expression of TP53 pathway genes was
also analyzed. RESULTS: According to the LINE-1 methylation results, overall
hypomethylation was observed along the normal-adenoma-carcinoma sequence. Within
top50 differential methylated regions (DMRs), in AD-N comparison TP73, NGFR,
PDGFRA genes were hypermethylated, FMN1, SLC16A7 genes were hypomethylated. In
CRC-N comparison DKK2, SDC2, SOX1 genes showed hypermethylation, while ERBB4,
CREB5, CNTN1 genes were hypomethylated. In certain mutation hot spot regions
significant DNA methylation alterations were detected. The TP53 gene body was
addressed by hypermethylation in adenomas. APC, TP53 and KRAS mutations were
found in 30, 15, 21% of adenomas, and in 29, 53, 29% of CRCs, respectively. mRNA
expression changes were observed in several TP53 pathway genes showing promoter
methylation alterations. CONCLUSIONS: DNA methylation with consecutive phenotypic
effect can be observed in a high number of promoter and gene body regions through
CRC development.
PMID- 29945575
TI - School and classroom effects on Daily Physical Activity (DPA) policy
implementation fidelity in Ontario classrooms: a multi-level analysis.
AB - BACKGROUND: This paper examines school and classroom effects on Daily Physical
Activity (DPA) policy implementation in classrooms in Ontario, Canada. In 2005
the Ontario Ministry of Education mandated a policy requiring school boards to
"ensure that all elementary students, including students with special needs, have
a minimum of twenty minutes of sustained MVPA each school day during
instructional time". Based on an adaptation of Chaudoir's conceptual framework,
this paper contributes to understanding the extent to which school factors (as
reported by administrators) and classroom factors (as reported by teachers) are
associated with policy implementation fidelity at the classroom level. METHODS:
Cross-sectional online surveys were conducted in 2014 with elementary school
administrators and teachers, based on representative random samples of schools
and classrooms. A measure assessing implementation fidelity was developed from
the six required components of the policy and for this paper fidelity at the
classroom level is treated as the outcome variable. Several school- and classroom
level measures were also included in the surveys and a number of these were
selected for inclusion here. Data from the two surveys were merged and selected
variables were included in the multi-level analysis. Two-level logistic
regression models were conducted to account for nesting of classrooms within
schools and a series of models were conducted to identify factors associated with
implementation fidelity. RESULTS: The analytic sample for this study included 170
school administrators and 307 classroom teachers from corresponding schools.
Findings from the multi-level logistic regression analyses indicated that only
classroom/teacher-level factors were significantly associated with implementation
fidelity at the classroom level. None of the school/administrator predictors were
significantly related to fidelity. The most parsimonious model included five
significant classroom/teacher predictors: teachers' perception of DPA as
realistic and achievable; confidence (self-efficacy); scheduling DPA in
timetables; lack of space; and lack of time. CONCLUSIONS: Findings from the study
indicate the theoretical and practical importance of addressing classroom and
teacher factors since they are most proximal to implementation fidelity to the
policy. Several of these factors also reflect complex structural and
organizational contexts, indicating that a systems approach to understanding and
supporting DPA implementation fidelity is warranted.
PMID- 29945576
TI - Retraction Note: Inequities in coverage of smokefree space policies within the
United States.
AB - The authors have retracted this article [1] because of an error with the data
extraction process.
PMID- 29945577
TI - Evaluation of root resorption after comprehensive orthodontic treatment using
cone beam computed tomography (CBCT): a meta-analysis.
AB - BACKGROUND: Orthodontic treatment can result in root resorption (RR). Traditional
two-dimensional (2D) data exhibit magnification, deformation and positioning
problems. Cone beam computed tomography (CBCT) contains more accurate three
dimensional (3D) information. This study identified and qualified the extent and
location of root resorption using cone beam computed tomography (CBCT) after
comprehensive orthodontic treatment. METHODS: Studies comparing the RR before and
after comprehensive orthodontic treatment using CBCT were identified using
electronic searches of databases, including Cochrane, PubMed, EMBASE, China
National Knowledge Infrastructure (CNKI) and Web of Science, and manual searches
in relevant journals and the reference lists of the included studies until Oct
25, 2017. The extraction of data and the risk of bias evaluation were conducted
by two investigators independently. The methodological quality of the included
studies was assessed using the methodological index for non-randomized studies
(MINORS). Studies that reported the length and volume of teeth were used for
quantitative analyses. RESULTS: Twelve studies were included in the meta
analysis. The length of all teeth after intervention was significantly shorter
than that before treatment (MD = 0.80, 95% CI 0.56, 1.03, P < 0.00001). The
sequence of RR from heaviest to lightest was maxillary lateral incisors,
maxillary central incisors, mandibular anterior teeth, and maxillary canines.
Studies were divided into two subgroups based on the use of tooth extraction.
Root shortening after treatment was observed in both groups, and extraction
caused more root resorption than was observed in the non-extraction group.
CONCLUSIONS: There were different degrees of root resorption after orthodontics,
but it was clinically acceptable. Root resorption established in CBCT research
was less serious and more accurate than that observed in the two-dimensional
research. Current evidence suggests that root length and volume were reduced
after orthodontic treatment. The order of the amount of RR was maxillary lateral
incisors, maxillary central incisors and mandibular anterior teeth. Most of the
articles were complicated by different confounding factors. Therefore, more high
quality clinical trials are needed to determine the risk factors of root
resorption and optimal protocols for treatment and to draw more reliable
conclusions.
PMID- 29945578
TI - Piloting online self-audit of methadone treatment in Irish general practice:
results, reflections and educational outcomes.
AB - BACKGROUND: Work based learning underpins the training and CPD of medical
practitioners. Medical audit operates on two levels; individual self-assessment
and professional/practice development. In Ireland, annual practice improvement
audit is an essential requirement for the successful completion of continuous
professional development (CPD) as determined by the regulatory body, the Irish
Medical Council. All general practice (GP) doctors providing methadone
maintenance treatment (MMT) in Ireland have a contractual obligation to partake
in a yearly methadone practice audit. The Irish College of General Practitioners
(ICGP) as national training provider is tasked to facilitate this annual audit
process. The purpose of this audit is to assess the quality of care provided to
patients against an agreed set of national standards, enhance learning, and
promote practice improvement and reflective practice. The aim was to present an
online MTP self-audit and evaluate results from a 12-month pilot among GPs
providing MMT in Ireland. METHODS: A mixed method study describing three phases
(design and development, pilot/implementation and evaluation) of a new online
self -audit tool was conducted. Descriptive and thematic analysis of audit and
evaluation data was conducted. RESULTS: Survey Monkey is a suitable software
package for the development and hosting of an easy to use online audit for MMT
providing doctors. Analysis of the audit results found that the majority of GPs
scored 80% or over for the 25 identified essential criteria for MMT provision.
The evaluation of the GP audit experience underscores the positive outcomes of
the online self-audit in terms of improving practice systems, encouraging
reflective practice, enhanced patient care and doctor commitment to continued
provision of MMT in addiction clinics and in primary care. CONCLUSIONS: Results
from this audit demonstrate a high level of compliance with best practise MMT
guidelines by Irish GPs providing MMT. The online self-audit process was well
received and encouraged reflective practice. The audit process hinged on the
individual GP's ability to review and critically analyse their professional
practice, and manage change. This model of audit could be adapted and used to
monitor the management of other chronic illnesses in general practice.
PMID- 29945579
TI - Mobile learning in medicine: an evaluation of attitudes and behaviours of medical
students.
AB - BACKGROUND: Mobile learning (mLearning) devices (such as tablets and smartphones)
are increasingly part of the clinical environment but there is a limited and
somewhat conflicting literature regarding the impact of such devices in the
clinical learning environment. This study aims to: assess the impact of mLearning
devices in the clinical learning environment on medical students' studying
habits, attitudes towards mobile device supported learning; and the perceived
reaction of clinicians and patients to the use of these devices as part of
learning in the clinical setting. METHODS: Over three consecutive academic years,
18 cohorts of medical students (total n = 275) on a six-week rotation at a large
teaching hospital in London were supplied with mLearning devices (iPad mini) to
support their placement-based learning. Feedback on their experiences and
perceptions was collected via pre- and post-use questionnaires. RESULTS: The
results suggest mLearning devices have a positive effect on the students'
perceived efficiency of working, while experience of usage not only confirmed pre
existing positive opinions about devices but also disputed some expected
limitations associated with mLearning devices in the clinical workplace. Students
were more likely to use devices in 'down-time' than as part of their clinical
learning. As anticipated, both by users and from the literature, universal
internet access was a major limitation to device use. The results were
inconclusive about the student preference for device provision versus supporting
a pre-owned device. CONCLUSION: M-learning devices can have a positive impact on
the learning experiences medical students during their clinical attachments. The
results supported the feasibility of providing mLearning devices to support
learning in the clinical environment. However, universal internet is a
fundamental limitation to optimal device utilisation.
PMID- 29945580
TI - Neighborhood deprivation and biomarkers of health in Britain: the mediating role
of the physical environment.
AB - BACKGROUND: Neighborhood deprivation has been consistently linked to poor
individual health outcomes; however, studies exploring the mechanisms involved in
this association are scarce. The objective of this study was to investigate
whether objective measures of the physical environment mediate the association
between neighborhood socioeconomic deprivation and biomarkers of health in
Britain. METHODS: We linked individual-level biomarker data from Understanding
Society: The UK Household Longitudinal Survey (2010-2012) to neighborhood-level
data from different governmental sources. Our outcome variables were forced
expiratory volume in 1 s (FEV1%; n=16,347), systolic blood pressure (SBP;
n=16,846), body mass index (BMI; n=19,417), and levels of C-reactive protein
(CRP; n=11,825). Our measure of neighborhood socioeconomic deprivation was the
Carstairs index, and the neighborhood-level mediators were levels of air
pollutants (sulphur dioxide [SO2], particulate matter [PM10], nitrogen dioxide
[NO2], and carbon monoxide [CO]), green space, and proximity to waste and
industrial facilities. We fitted a multilevel mediation model following a
multilevel structural equation framework in MPlus v7.4, adjusting for age,
gender, and income. RESULTS: Residents of poor neighborhoods and those exposed to
higher pollution and less green space had worse health outcomes. However, only
SO2 exposure significantly and partially mediated the association between
neighborhood socioeconomic deprivation and SBP, BMI, and CRP. CONCLUSION:
Reducing air pollution exposure and increasing access to green space may improve
population health but may not decrease health inequalities in Britain.
PMID- 29945581
TI - Development and validation of an integrated DNA walking strategy to detect GMO
expressing cry genes.
AB - BACKGROUND: Recently, an integrated DNA walking strategy has been proposed to
prove the presence of GMO via the characterisation of sequences of interest,
including their transgene flanking regions and the unnatural associations of
elements in their transgenic cassettes. To this end, the p35S, tNOS and t35S
pCAMBIA elements have been selected as key targets, allowing the coverage of most
of GMO, EU authorized or not. In the present study, a bidirectional DNA walking
method anchored on the CryAb/c genes is proposed with the aim to cover additional
GMO and additional sequences of interest. RESULTS: The performance of the
proposed bidirectional DNA walking method anchored on the CryAb/c genes has been
evaluated in a first time for its feasibility using several GM events possessing
these CryAb/c genes. Afterwards, its sensitivity has been investigated through
low concentrations of targets (as low as 20 HGE). In addition, to illustrate its
applicability, the entire workflow has been tested on a sample mimicking
food/feed matrices analysed in GMO routine analysis. CONCLUSION: Given the
successful assessment of its performance, the present bidirectional DNA walking
method anchored on the CryAb/c genes can easily be implemented in GMO routine
analysis by the enforcement laboratories and allows completing the entire DNA
walking strategy in targeting an additional transgenic element frequently found
in GMO.
PMID- 29945582
TI - Discourses on the postcoital pill in young women.
AB - BACKGROUND: Emergency contraception (EC) is an effective postcoital contraceptive
method for reducing the risk of unwanted pregnancy after unprotected intercourse.
The estimated effectiveness of EC is between 70 and 89% if taken within 72 h
following intercourse. Most of the studies carried out in Spain are quantitative
and from the perspective of health professionals. In this study, we intend to
explore the knowledge of, attitudes towards and discourse regarding the use of EC
in women aged 15 to 25 years. METHODS: Sample: A qualitative study including in
depth interviews with 19 women between 15 and 25 years of age was performed.
INCLUSION CRITERIA: Participants were natives of Spain or of a Latin American
country. Segmentation criteria: Participants had experience in the use of EC.
DATA COLLECTION: Participants were selected by health care informants and by the
snowball technique among university students. DATA ANALYSIS: A thematic analysis
was performed. Preliminary analyses were made during the course of the field work
to adapt the script and to assess data saturation. A preliminary code tree was
developed by two researchers, and the coding of the text was done with the
Atlas.ti 5.0 software. RESULTS: EC is perceived positively by women. They do not
express issues with taking it, although some feel guilty. The reason for taking
EC is to avoid unwanted pregnancy and abortion. Women also feel that EC should be
used in moderation. False beliefs and misconceptions regarding EC are held: EC
delivers an excess of hormones, induces abortion and causes severe side effects.
Women mention that the health professionals who provide EC have moral beliefs.
Women use it because of condom breakage associated with their first coital
relations. CONCLUSIONS: The results of this study have public health
implications: The sexual-affective health education received by young people
should incorporate clear information about the mechanism of action of the EC pill
and its side effects together with empowerment strategies addressing guilt and
moralistic messages. Programmes and training activities for health professionals
must be designed to prevent the communication of inappropriate messages such as
those that exaggerate the side effects of EC and those that promote fear and
guilt, because they represent a barrier to the responsible use of this
medication.
PMID- 29945583
TI - Engineering Geobacillus thermodenitrificans to introduce cellulolytic activity;
expression of native and heterologous cellulase genes.
AB - BACKGROUND: Consolidated bioprocessing (CBP) is a cost-effective approach for the
conversion of lignocellulosic biomass to biofuels and biochemicals. The enzymatic
conversion of cellulose to glucose requires the synergistic action of three types
of enzymes: exoglucanases, endoglucanases and beta-glucosidases. The
thermophilic, hemicellulolytic Geobacillus thermodenitrificans T12 was shown to
harbor desired features for CBP, although it lacks the desired endo and
exoglucanases required for the conversion of cellulose. Here, we report the
expression of both endoglucanase and exoglucanase encoding genes by G.
thermodenitrificans T12, in an initial attempt to express cellulolytic enzymes
that complement the enzymatic machinery of this strain. RESULTS: A metagenome
screen was performed on 73 G. thermodenitrificans strains using HMM profiles of
all known CAZy families that contain endo and/or exoglucanases. Two putative
endoglucanases, GE39 and GE40, belonging to glucoside hydrolase family 5 (GH5)
were isolated and expressed in both E. coli and G. thermodenitrificans T12.
Structure modeling of GE39 revealed a folding similar to a GH5 exo-1,3-beta
glucanase from S. cerevisiae. However, we determined GE39 to be a beta-xylosidase
having pronounced activity towards p-nitrophenyl-beta-D-xylopyranoside. Structure
modelling of GE40 revealed its protein architecture to be similar to a GH5
endoglucanase from B. halodurans, and its endoglucanase activity was confirmed by
enzymatic activity against 2-hydroxyethylcellulose, carboxymethylcellulose and
barley beta-glucan. Additionally, we introduced expression constructs into T12
containing Geobacillus sp. 70PC53 endoglucanase gene celA and both endoglucanase
genes (M1 and M2) from Geobacillus sp. WSUCF1. Finally, we introduced expression
constructs into T12 containing the C. thermocellum exoglucanases celK and celS
genes and the endoglucanase celC gene. CONCLUSIONS: We identified a novel G.
thermodenitrificans beta-xylosidase (GE39) and a novel endoglucanase (GE40) using
a metagenome screen based on multiple HMM profiles. We successfully expressed
both genes in E. coli and functionally expressed the GE40 endoglucanase in G.
thermodenitrificans T12. Additionally, the heterologous production of active
CelK, a C. thermocellum derived exoglucanase, and CelA, a Geobacillus derived
endoglucanase, was demonstrated with strain T12. The native hemicellulolytic
activity and the heterologous cellulolytic activity described in this research
provide a good basis for the further development of G. thermodenitrificans T12 as
a host for consolidated bioprocessing.
PMID- 29945585
TI - Vascular endothelial growth factor expression and their action in the synovial
membranes of patients with painful knee osteoarthritis.
AB - BACKGROUND: Research suggests that vascular endothelial growth factor (VEGF)
levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively
correlated with KOA severity. The relationship between synovial VEGF levels and
pain in human KOA patients is not fully understood, and the role of VEGF in the
pain pathway remains unclear. METHODS: We harvested synovial membrane (SM) from
102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence
[K/L] grade 2-4) during total knee arthroplasty. Patients scored their pain on a
0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with
strong/severe (VAS >= 6) and mild/moderate pain (VAS < 6) were compared.
Correlations between VAS and VEGF mRNA expression were investigated. To
investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF
and the neuropeptide apelin was determined by immunohistochemical analyses. To
investigate the role of VEGF in regulating apelin expression, SM cells were
exposed to VEGF. RESULTS: VEGF expression in the VAS >= 6 group was significantly
greater than expression in the VAS < 6 group. Expression levels of VEGF were also
positively correlated with VAS. VEGF-positive cells were identified in the lining
of the SM. Expression of apelin mRNA and protein were significantly elevated in
SM cells treated with exogenous VEGF compared to those treated with vehicle.
CONCLUSION: Synovial VEGF may be involved in pain pathways in KOA and its action
may be mediated by apelin.
PMID- 29945584
TI - Lipodystrophy diagnosis in people living with HIV/AIDS: prediction and validation
of sex-specific anthropometric models.
AB - BACKGROUND: Body composition alterations, or lipodystrophy, can lead to serious
health problems in people living with HIV/AIDS (PLWHA). The objectives of this
study are to predict and validate sex-specific anthropometric predictive models
for the diagnosis of lipodystrophy in PLWHA. METHODS: A cross-sectional design
was employed to recruit 106 PLWHA (men = 65 and women = 41) in Brazil during 2013
2014. They were evaluated using dual-energy X-ray absorptiometry, and 19 regions
of body perimeters and 6 skinfold thicknesses were taken. Sex-specific predictive
models for lipodystrophy diagnosis were developed through stepwise linear
regression analysis. Cross-validations using predicted residual error sum of
squares was performed to validate each predictive model. RESULTS: Results support
the use of anthropometry for the diagnosis of lipodystrophy in men and women
living with HIV/AIDS. A high power of determination with a small degree of error
was observed for lipodystrophy diagnosis for men in model six (r2 = 0.77, SEE =
0.14, r2PRESS = 0.73, SEE PRESS = 0.15), that included ratio of skinfold
thickness of subscapular to medial calf, skinfold thickness of thigh, body
circumference of waist, formal education years, time of diagnosis to HIV months,
and type of combined antiretroviral therapy (cART) (with protease inhibitor
"WI/PI = 1" or without protease inhibitor "WO/PI = 0"); and model five for women
(r2 = 0.78, SEE = 0.11, r2PRESS = 0.71, SEE PRESS = 0.12), that included skinfold
thickness of thigh, skinfold thickness of subscapular, time of exposure to cART
months, body circumference of chest, and race (Asian) ("Yes" for Asian race = 1;
"No" = 0). CONCLUSIONS: The proposed anthropometric models advance the field of
public health by facilitating early diagnosis and better management of
lipodystrophy, a serious adverse health effect experienced by PLWHA.
PMID- 29945586
TI - Implementation of preemptive fluid strategy as a bundle to prevent fluid overload
in children with acute respiratory distress syndrome and sepsis.
AB - BACKGROUND: Fluid overload (FO) is associated with unfavorable outcomes in
critically ill children. Clinicians are encouraged to avoid FO; however,
strategies to avoid FO are not well-described in pediatrics. Our aim was to
implement a bundle strategy to prevent FO in children with sepsis and pARDS and
to compare the outcomes with a historical cohort. METHODS: A quality improvement
initiative, known as preemptive fluid strategy (PFS) was implemented to prevent
early FO, in a 12-bed general PICU. Infants on mechanical ventilation (MV)
fulfilling pARDS and sepsis criteria were prospectively recruited. For
comparison, data from a historical cohort from 2015, with the same inclusion and
exclusion criteria, was retrospectively reviewed. The PFS bundle consisted of 1.
maintenance of intravenous fluids (MIVF) at 50% of requirements; 2. drug volume
reduction; 3. dynamic monitoring of preload markers to determine the need for
fluid bolus administration; 4. early use of diuretics; and 5. early initiation of
enteral feeds. The historical cohort treatment, the standard fluid strategy
(SFS), were based on physician preferences. Peak fluid overload (PFO) was the
primary outcome. PFO was defined as the highest FO during the first 72 h. FO was
calculated as (cumulative fluid input - cumulative output)/kg*100. Fluid
input/output were registered every 12 h for 72 h. RESULTS: Thirty-seven patients
were included in the PFS group (54% male, 6 mo (IQR 2,11)) and 39 with SFS
(64%male, 3 mo (IQR1,7)). PFO was lower in PFS (6.31% [IQR4.4-10]) compared to
SFS (12% [IQR8.4-15.8]). FO was lower in PFS compared to CFS as early as 12 h
after admission [2.4(1.4,3.7) v/s 4.3(1.5,5.5), p < 0.01] and maintained during
the study. These differences were due to less fluid input (MIVF and fluid
boluses). There were no differences in the renal function test. PRBC requirements
were lower during the first 24 h in the PFS (5%) compared to SFS (28%, p < 0.05).
MV duration was 81 h (58,98) in PFS and 118 h (85154) in SFS(p < 0.05). PICU LOS
in PFS was 5 (4, 7) and in SFS was 8 (6, 10) days. CONCLUSION: Implementation of
a bundle to prevent FO in children on MV with pARDS and sepsis resulted in less
PFO. We observed a decrease in MV duration and PICU LOS. Future studies are
needed to address if PFS might have a positive impact on health outcomes.
PMID- 29945587
TI - Methodological quality of teaching communication skills to undergraduate medical
students: a mapping review.
AB - BACKGROUND: Patient-clinician communication training is a core component of the
undergraduate medical program. As with all areas of medicine, the best available
evidence for teaching these skills should be incorporated into training programs.
Examining the volume, type and design-quality of publications in this field can
help to determine whether research is following a natural scientific progression
to inform interactional skills training. This study aimed to review: (i) whether
the proportion of publications examining teaching interactional skills to
undergraduate medical students by study type, across three time-periods (2007
2008, 2011-2012, 2015-2016), changed over time (i.e. measurement, descriptive or
interventions studies); and (ii) the proportion of intervention studies meeting
Cochrane Effective Practice and Organisation of Care (EPOC) research design
criteria. METHODS: Medline, PubMed, PsycInfo and the Cochrane Database were
searched for studies published in English from 2007 to 2016. Title and abstract
reviews were performed for the included years. Articles were examined against the
inclusion/exclusion criteria and those included were coded into descriptive,
measurement or intervention categories. RESULTS: A total of 243 relevant
publications were identified. Fifty-two were published from 2007 to 2008, 75 from
2011 to 2012 and 116 from 2015 to 2016. Most identified studies were descriptive
(63%), followed by measurement studies (22%) and intervention studies (15%). The
proportion of descriptive studies increased significantly over time. However, the
proportion of intervention studies did not change and the proportion of measures
studies significantly decreased. Of the 37 intervention studies identified within
the three time-periods, only 16 (43%) met EPOC study design criteria.
CONCLUSIONS: The largest proportion of identified studies were descriptive,
however, descriptive research is not sufficient to ensure communication skills
training can effectively improve interactions between clinicians and patients. A
more rigorous approach to research in this area is needed to inform education
strategies.
PMID- 29945590
TI - Differences and structural weaknesses of institutional mechanisms for health
research ethics: Burkina Faso, Palestine, Peru, and Democratic Republic of the
Congo.
AB - BACKGROUND: Regardless of national contexts, the institutions responsible for
research ethics, founded on international regulations, are all expected to be
structured and to operate in a common way. Our experience with several countries
on different continents, however, has raised questions in this regard. This
article examines the differences and structural weaknesses of ethics committees
in four countries (Burkina Faso, Palestine, Peru, and the Democratic Republic of
the Congo) where we have conducted the same socio-anthropological study in the
field of reproductive health. METHODS: In addition to recording our observations
during field surveys for this study, we performed a documentary review and
interviewed expert members of ethics committees, research participants, and
researchers who had experience with requesting ethics approvals for research
protocols in the field of social sciences and health. RESULTS: The results of
this study showed that, despite having the same mandate, the committees
functioned differently, while they all exhibited the same weaknesses. Thus, the
universalization and standardization of institutional conditions for applying
ethical standards in research still present problems that are, at the very least,
relevant. CONCLUSION: This study on ethics committees in four countries
demonstrated the profound influence of context on the ways in which different
institutions function and enforce regulations. In effect, in all social fields,
every innovation is infused by its context.
PMID- 29945589
TI - Emergency department 72-hour revisits among children with chronic diseases: a
Saudi Arabian study.
AB - BACKGROUND: Emergency Department (ED) revisits have often been used as an
indicator of medical care quality. This study aimed to quantify the frequency of
ED revisits within 72 h of discharge and identify its factors among children with
chronic diseases. METHODS: We designed a retrospective cohort study of children
with at least one chronic disease who were also under 18 years of age and had
attended and were discharged from the ED at King Abdullah Specialist Children's
Hospital (KASCH-RD), Riyadh, Saudi Arabia between April 19, 2015 and July 29,
2017. The outcome measure was the frequency of ED revisits during a period of 72
h after discharge. RESULTS: The study included 11,057 ED discharges of children
with at least one chronic disease. Their revisit rate was 1211 (11%), with 83
(6.9%) having had a second ED revisit within 72 h of ED discharge. According to
ICD-10 codes, the most common causes of ED revisits were respiratory, digestive,
genitourinary, symptoms, and external causes. Factors of frequent ED revisits
within 72 h were young age, institutional health insurance coverage, year of new
health information system (2015), external causes, and genitourinary. CONCLUSION:
The rate of 72-h ED revisits after discharge of children with chronic diseases
treated at KASCH-RD was relatively high, and was associated with young age,
institutional health insurance coverage, year of a new health information system
implementation, and external causes of ED visit. These study findings amplify the
need for intervention to reduce the rate of early ED revisits among children with
chronic diseases.
PMID- 29945588
TI - Social capital predicts accelerometry-measured physical activity among older
adults in the U.S.: a cross-sectional study in the National Social Life, Health,
and Aging Project.
AB - BACKGROUND: Older adults receive important health benefits from more robust
social capital. Yet, the mechanisms behind these associations are not fully
understood. Some evidence suggests that higher levels of social capital
ultimately affect health through alterations in physical activity (PA), but most
of this research has relied on self-reported levels of PA. The aim of this study
was to determine whether components of social capital, including social network
size and composition as well as the frequency of participation in various social
and community activities, were associated with accelerometry-measured PA levels
in a nationally representative sample of community-dwelling older adults (>= 62
years). METHODS: We conducted a cross-sectional analysis using data from the
wrist accelerometry sub-study (n = 738) within Wave 2 of the National Social,
Health, and Aging Project (NSHAP), a population-based longitudinal study that
collects extensive survey data on the physical, cognitive, and social health of
older adults. Participants' physical activity was measured with a wrist
accelerometer worn for 72 consecutive hours. We related seven, self-reported
social relationship variables (network size, network proportion friends, and
frequencies of socializing with friends and family, visiting with neighbors,
attending organized group meetings, attending religious services, and
volunteering) to accelerometer-measured PA (mean counts-per-minute) using
multivariate linear regression analysis, while adjusting for potential
confounders. RESULTS: Larger social networks (p = 0.042), higher network
proportion friends (p = 0.013), more frequent visiting with neighbors (p =
0.009), and more frequent attendance at organized group meetings (p = 0.035) were
associated with higher PA levels after controlling for demographic and health
covariates. Volunteering was significant prior to adjusting for covariates. No
significant associations were found between frequencies of socializing with
friends and relatives or attendance at religious services and PA. CONCLUSIONS:
This study suggests social capital is significantly related to objectively
measured PA levels among older adults, and that friendships as well as social
participation in groups and with neighbors may be particularly pertinent to PA.
These findings expand our understanding of and offer a potential mechanism
linking social relationships and overall health among older adults. They also
have implications for how we might motivate older adults to be more physically
active.
PMID- 29945591
TI - Introduction to Ethics and Global Health.
PMID- 29945593
TI - Ethics beyond ethics: the need for virtuous researchers.
AB - BACKGROUND: Research ethics boards (REBs) exist for good reason. By setting rules
of ethical behaviour, REBs can help mitigate the risk of researchers causing harm
to their research participants. However, the current method by which REBs promote
ethical behaviour does little more than send researchers into the field with a
set of rules to follow. While appropriate for most situations, rule-based
approaches are often insufficient, and leave significant gaps where researchers
are not provided institutional ethical direction. RESULTS: Through a discussion
of a recent research project about drinking and driving in South Africa, this
article demonstrates that if researchers are provided only with a set of rules
for ethical behaviour, at least two kinds of problems can emerge: situations
where action is required but there is no ethically good option (zungzwang ethical
dilemmas) and situations where the ethical value of an action can only be
assessed after the fact (contingent ethical dilemmas). These dilemmas highlight
and help to articulate what we already intuit: that a solely rule-based approach
to promoting ethical research is not always desirable, possible, effective, or
consistent. CONCLUSIONS: In this article, I argue that to better encourage
ethical behaviour in research, there is a need to go beyond the rules and
regulations articulated by ethics boards, and focus more specifically on creating
and nurturing virtuous researchers.
PMID- 29945592
TI - The ethics of relationality in implementation and evaluation research in global
health: reflections from the Dream-A-World program in Kingston, Jamaica.
AB - BACKGROUND: Despite recent developments aimed at creating international
guidelines for ethical global health research, critical disconnections remain
between how global health research is conducted in the field and the
institutional ethics frameworks intended to guide research practice. DISCUSSION:
In this paper we attempt to map out the ethical tensions likely to arise in
global health fieldwork as researchers negotiate the challenges of balancing
ethics committees' rules and bureaucracies with actual fieldwork processes in
local contexts. Drawing from our research experiences with an implementation and
evaluation project in Jamaica, we argue that ethical research is produced through
negotiated spaces and reflexivity practices that are centred on relationships
between researchers and study participants and which critically examine issues of
positionality and power that emerge at multiple levels. In doing so, we position
ethical research practice in global health as a dialectical movement between the
spoken and unspoken, or, more generally, between operationalized rules and the
embodied relational understanding of persons. Global health research ethics
should be premised not upon passive accordance with existing guidelines on
ethical conduct, but on tactile modes of knowing that rely upon being engaged
with, and responsive to, research participants. Rather than focusing on the
operationalization of ethical practice through forms and procedures, it is
crucial that researchers recognize that each ethical dilemma encountered during
fieldwork is unique and rooted in social contexts, interpersonal relationships,
and personal narratives.
PMID- 29945594
TI - Right to health and social justice in Bangladesh: ethical dilemmas and
obligations of state and non-state actors to ensure health for urban poor.
AB - BACKGROUND: The world is urbanizing rapidly; more than half the world's
population now lives in urban areas, leading to significant transition in
lifestyles and social behaviours globally. While offering many advantages, urban
environments also concentrate health risks and introduce health hazards for the
poor. In Bangladesh, although many public policies are directed towards equity
and protecting people's rights, these are not comprehensively and inclusively
applied in ways that prioritize the health rights of citizens. The country is
thus facing many issues that raise moral and ethical concerns. METHODS: A
narrative literature review was conducted between October 2016 and November 2017
on issues related to social justice, health, and human rights in urban
Bangladesh. The key questions discussed here are: i) ethical dilemmas and
inclusion of the urban poor to pursue social justice; and ii) the ethical
obligations and moral responsibilities of the state and non-state sectors in
serving Bangladesh's urban poor. Using a Rawlsian theory of equality of
opportunity to ensure social justice, we identified key health-related ethical
issues in the country's rapidly changing urban landscape, especially among the
poor. RESULTS: We examined ethical dilemmas in Bangladesh's health system through
the rural-urban divide and the lack of coordination among implementing agencies.
The unregulated profusion of the private sector and immoral practices of service
providers result in high out-of-pocket expenditures for urban poor, leading to
debt and further impoverishment. We also highlight policy and programmatic gaps,
as well as entry points for safeguarding the right to health for Bangladeshi
citizens. CONCLUSIONS: The urban health system in Bangladesh needs a reform in
which state and non-state actors should work together, understanding and
acknowledging their moral responsibilities for improving the health of the urban
poor by engaging multiple sectors. The social determinants of health should be
taken into account when formulating policies and programs to achieve universal
health coverage and ensure social justice for the urban poor in Bangladesh.
PMID- 29945595
TI - Deconstructing the notion of "global health research partnerships" across
Northern and African contexts.
AB - BACKGROUND: Global health conceives the notion of partnership between North and
South as central to the foundations of this academic field. Indeed, global health
aspires to an equal positioning of Northern and Southern actors. While the notion
of partnership may be used to position the field of global health morally, this
politicization may mask persisting inequalities in global health. In this paper,
we reflect on global health partnerships by revisiting the origins of global
health and deconstructing the notion of partnership. We also review promising
initiatives that may help to rebalance the relationship. RESULTS AND DISCUSSION:
Historical accounts are helpful in unpacking the genesis of collaborative
research between Northerners and Southerners - particularly those coming from the
African continent. In the 1980s, the creation of a scientific hub of working
relationships based on material differences created a context that was bound to
create tensions between the alleged "partners". Today, partnerships provide
assistance to underfunded African research institutions, but this assistance is
often tied with hypotheses about program priorities that Northern funders require
from their Southern collaborators. African researchers are often unable to lead
or contribute substantially to publications for lack of scientific writing
skills, for instance. Conversely, academics from African countries report
frustrations at not being consulted when the main conceptual issues of a research
project are discussed. However, in the name of political correctness, these
frustrations are not spoken aloud. Fortunately, initiatives that shift
paternalistic programs to formally incorporate a mutually beneficial design at
their inception with equal input from all stakeholders are becoming increasingly
prominent, especially initiatives involving young researchers. CONCLUSION:
Several concrete steps can be undertaken to rethink partnerships. This goes hand
in hand with reconceptualizing global health as an academic discipline, mainly
through being explicit about past and present inequalities between Northern and
Southern universities that this discipline has thus far eluded. Authentic and
transformative partnerships are vital to overcome the one-sided nature of many
partnerships that can provide a breeding-ground for inequality.
PMID- 29945597
TI - Community involvement in biomedical research conducted in the global health
context; what can be done to make it really matter?
AB - BACKGROUND: Community involvement in research has been advocated by researchers,
communities, regulatory agencies, and funders with the aim of reinforcing
subjects' protection and improving research efficiency. Community involvement
also has the potential to improve dissemination, uptake, and implementation of
research findings. The fields of community based participatory research conducted
with indigenous populations and of participatory action research offer a large
base of experience in community involvement in research. Rules on involving the
population affected when conducting research have been established in these
fields. But what is the role of community engagement in clinical research and
observational studies conducted in biomedical research outside of these specific
areas? More than 20 years ago, in the field of HIV medicine, regulatory bodies
and funding agencies (such as the US National Institutes of Health) recommended
the constitution of a formal organism, the Community Advisory Board (CAB), as
part of the study requirements for HIV trials. More recently, CABs have been
adopted and used in other fields of medical research, such as malaria. CABs are
not without limitations, however, and there is little research on the
effectiveness of their use in achieving community protection and participation.
Nevertheless, CABs could be a model to import into clinical trials and
observational research where no alternative model of community representation is
currently being used. CONCLUSIONS: Allocating more resources to training and
shifting more power to community representatives could be part of the solution to
current CAB limitations. However, for researchers to be able to apply these
recommendations on community involvement, certain conditions need to be met. In
particular, funding agencies need to recognize the human and financial resources
required for serious community involvement, and the academic environment needs to
take community involvement into account when appraising, mentoring, and training
researchers.
PMID- 29945598
TI - A reflection on the challenge of protecting confidentiality of participants while
disseminating research results locally.
AB - BACKGROUND: Researchers studying health systems in low-income countries face a
myriad of ethical challenges throughout the entire research process. In this
article, we discuss one of the greatest ethical challenges that we encountered
during our fieldwork in West Africa: the difficulty of protecting the
confidentiality of participants (or groups of participants) while locally
disseminating results of health systems research to stakeholders. METHODS: This
reflection is based on experiences of authors involved in conducting evaluative
research of interventions aimed at improving health systems in West Africa. Our
observation and collaboration with the research projects' stakeholders informed
our analysis. Examples from two research projects illustrate the issues raised.
RESULTS: We found that in some cases there is a risk that local stakeholders may
be able to identify research participants, or at least groups of participants,
during the dissemination of results, even if they are anonymized. Four factors
can interact and influence this challenge: 1) hierarchical structure, 2) small
milieu, 3) immersion in a few sites, and 4) vested interests of decision-makers.
For example, local stakeholders can sometimes find out when and where the data
were collected. Moreover, health systems, especially rural healthcare centres, in
West African countries can be small settings, so people often know each other.
Some types of participants have unique characteristics or positions in the health
system that may make them more easily identifiable by local stakeholders familiar
with the environment. We identified a number of potential strategies that can
help researchers minimize this difficulty and improve ethical research practices.
These strategies pertain to the development of the study design, the process of
obtaining informed consent, the dissemination of results, and the researchers'
reflexivity. CONCLUSION: Researchers must develop and adopt strategies that
enable them to respect their promise of confidentiality while effectively
disseminating sometimes sensitive results. Reflections surrounding ethical issues
in global health research should be deepened to better address how to manage
competing ethical responsibilities while promoting valuable research uptake.
PMID- 29945596
TI - Is fast reversal and early surgery (within 24 h) in patients on warfarin
medication with trochanteric hip fractures safe? A case-control study.
AB - BACKGROUND: Hip fracture patients in general are elderly and they often have
comorbidities that may necessitate anticoagulation treatment, such as warfarin.
It has been emphasized that these patients benefit from surgery without delay to
avoid complications and reduce mortality. This creates a challenge for patients
on warfarin and especially for those with trochanteric or subtrochanteric hip
fractures treated with intramedullary nailing, as this is associated with
increased bleeding compared to other types of hip fractures and surgical methods.
The aim of the study was to evaluate if early surgery (within 24 h) of
trochanteric or subtrochanteric hip fractures using intramedullary nailing is
safe in patients on warfarin treatment after fast reversal of the warfarin
effect. METHODS: A retrospective case-control study including 198 patients: 99
warfarin patients and 99 patients without anticoagulants as a 1:1 ratio control
group matched for age, gender and surgical implant. All patients were operated
within 24 h with a cephalomedullary nail due to a trochanteric or subtrochanteric
hip fracture. All patients on warfarin were reversed if necessary to INR <= 1.5
before surgery using vitamin K and/or four-factor prothrombin complex concentrate
(PCC). Per- and postoperative data, transfusion rates, adverse events and
mortality was compared. RESULTS: There were no significant differences in the
calculated blood-loss, in-house adverse events or mortality (in-house, 30-day or
1-year) between the groups. There were no significant differences in the pre- or
peroperative transfusions rates, but there was an increased rate of postoperative
transfusions in the control group (p = 0.02). CONCLUSION: We found that surgical
treatment with intramedullary nailing within 24 h of patients with trochanteric
or subtrochanteric hip fractures on warfarin medication after reversing its
effect to INR <= 1.5 using vitamin K and/or PCC is safe.
PMID- 29945599
TI - Commodification of care and its effects on maternal health in the Noun division
(West Region - Cameroon).
AB - BACKGROUND: Since the mid-1980s, there has been a gradual ethical drift in the
provision of maternal care in African health facilities in general, and in
Cameroon in particular, despite government efforts. In fact, in Cameroon, an
increasing number of caregivers are reportedly not providing compassionate care
in maternity services. Consequently, many women, particularly the financially
vulnerable, experience numerous difficulties in accessing these health services.
In this article, we highlight the unequal access to care in public maternity
services in Cameroon in general and the Noun Division in particular. METHODS: For
this study, in addition to documentary review, two qualitative data collection
techniques were used: direct observation and individual interviews. Following the
field work, the observation data were categorized and analyzed to assess their
relevance and significance in relation to the topics listed in the observation
checklist. Interviews were recorded using a dictaphone; they were subsequently
transcribed and the data categorized and coded. After this stage, an analysis
grid was constructed for content analysis of the transcripts, to study the
frequency of topics addressed during the interviews, as well as divergences and
convergences among the respondents. RESULTS: The results of this data analysis
showed that money has become the driving force in service provision. As such, it
is the patient's economic capital that counts. Considered "clients", pregnant
women without sufficient financial resources wait long hours in corridors; some
die in pain under the indifferent gaze of the professionals who are supposed to
take care of them. In sharp contrast, the findings revealed that financially
privileged patients are able to bribe caregivers to attract their favour and
obtain prompt, careful, and effective care. CONCLUSION: These ethical abuses
observed in the Noun public health facilities drive women to use, from the
beginning of their pregnancies to the delivery, only healthcare delivered by
traditional health attendants.
PMID- 29945600
TI - Membrane-bound and soluble forms of an NMDA receptor extracellular domain retain
epitopes targeted in auto-immune encephalitis.
AB - BACKGROUND: Anti-NMDA receptor encephalitis (ANRE) is a potentially lethal
disease attributed to auto-antibodies against the N-methyl-D-aspartate receptor
(NMDAR). Full recovery is possible if therapy is initiated early in the disease
course. Detection of ANRE antibodies in the cerebrospinal fluid (CSF) is
essential for diagnosis. The assays for ANRE-associated IgGs often rely on cells
transiently transfected with NMDAR genes. A cell line that stably expresses
pathogenic NMDAR epitopes could improve standardization of the assays and provide
antigen that could be used in commercial solid state assay systems. RESULTS: We
expressed the amino terminal domain (ATD) of the GluN1 NMDAR subunit (NR1) as a
fusion protein on the outer plasma membrane of 293T cells, creating a stable cell
population (293T-ATD) that is recognized by ANRE patient monoclonal antibodies in
flow cytometry and immunofluorescence assays. The ATD fusion protein also
contains a Myc tag and a 6XHIS tag, which provide functionality for immunoassays
and antigen purification, and a TEV protease site, which allows the ATD domain to
be specifically released from the cells in essentially pure form. ATD mobilized
from the 293T ATD cell line maintained the pathogenic ANRE epitopes in ELISA
binding assays. CSF (3/4) and sera (4/4) from ANRE patients also bound the 293T
ATD cell line, whereas normal CSF and sera did not. CONCLUSIONS: The 293T-ATD
cell line is potentially adaptable to a variety of formats to identify antibodies
associated with ANRE, including cell-based and soluble antigen formats, and
demonstrates a useful method to produce complex proteins for research, drug
discovery, and clinical diagnosis.
PMID- 29945602
TI - Atypical CHARGE associated with a novel frameshift mutation of CHD7 in a Chinese
neonatal patient.
AB - BACKGROUND: CHARGE syndrome is an autosomal dominant malformation disorder caused
by heterozygous loss of function mutations in the chromatin remodeler CHD7, which
has been estimated to occur in 1:10,000 births worldwide. It is a genetic
disorder closely resembles other pattern of anomalies. Genetic testing should be
pointed out as a useful method for clinical diagnosis. CASE PRESENTATION: A
female infant was the second child born to a 33-year-old, gravida 3, para 2
mother. The infant was born at 37 + 4 weeks of gestation with a birth weight of
2440 g (- 1.1 S.D.). Clinical examination showed atypical CHARGE syndrome, with
choanal atresia, a heart defect, and sensorineural deafness. Genomic DNA was
extracted from peripheral venous blood sample using molecular biological
technique. We used the Illumina TruSigt One sequencing panel on the MiSeq next-
generation sequencing (NGS) platform for mutation screening and found a novel
frameshift mutation in chromodomain helicase DNA binding protein 7 (CHD7;
c.4656dupT). This mutation results in a new reading frame ending in
p.(Ile1553fs). At the first month of age, the patient had a posterior nostril
plasty operation by nasal endoscope. At the second month of age, she had patent
ductus arteriosus ligation surgery. At the 4th month of age, she was discharged
from the hospital. CONCLUSIONS: Our findings further reveal that patients should
not be rejected for CHD7 mutational analysis even if they do not fulfill CHARGE
syndrome Verloes criteria.
PMID- 29945601
TI - Medication adherence in pregnant women with human immunodeficiency virus
receiving antiretroviral therapy in sub-Saharan Africa: a systematic review.
AB - BACKGROUND: The use of antiretroviral therapy (ART) is a core strategy proposed
by the World Health Organization in preventing mother to child transmission
(MTCT) of HIV. This systematic review aimed to examine the enablers and barriers
of medication adherence among HIV positive pregnant women in sub-Saharan Africa.
METHODS: We used the following keywords: HIV AND (Pregnancy OR Pregnant*) AND
(PMTCT OR "PMTCT Cascade" OR "Vertical Transmission" OR "Mother-to-Child") AND
(Prevent OR Prevention) AND (HAART OR "Antiretroviral Therapy" OR "Triple
Therapy") AND (Retention OR Concordance OR Adherence OR Compliance) to conduct
electronic searches in the following databases: MEDLINE Complete (1916-Dec 2017),
Embase (1947-Dec 2017), Global Health (1910-Dec 2017) and CINAHL Complete (1937
Dec 2017). Of the four databases searched, 401 studies were identified with 44
meeting the inclusion criteria. Seven studies were added after searching
reference lists of included articles, resulting in 51 articles in total. RESULTS:
The review demonstrated that stigma, cost of transportation, food deprivation and
a woman's disclosure or non-disclosure of her HIV status to a partner, family and
the community, could limit or define the extent of her adherence to prescribed
antiretroviral drugs during pregnancy. Furthermore, the review indicated that
knowledge of HIV status, either before or during pregnancy, was significantly
associated with medication adherence. Women who knew their HIV status before
pregnancy demonstrated good adherence while women who found out their HIV
infection status during pregnancy were linked with non-adherence to ART.
CONCLUSION: This review revealed several barriers and enablers of adherence among
pregnant women taking ART in sub-Saharan Africa. Major barriers included the fear
of HIV infection status disclosure to partners and family members, stigma and
discrimination. A major enabler of adherence in women taking ART was women's
knowledge of their HIV status prior to becoming pregnant. Enhanced effort is
needed to facilitate women's knowledge of their HIV status before pregnancy to
enable disease acceptance and management, and to support pregnant women and her
partner and family in dealing with fear, stigma and discrimination about HIV.
PMID- 29945603
TI - The effect of positive psychology interventions on well-being and distress in
clinical samples with psychiatric or somatic disorders: a systematic review and
meta-analysis.
AB - BACKGROUND: Although positive psychology interventions (PPIs) show beneficial
effects on mental health in non-clinical populations, the current literature is
inconclusive regarding its effectiveness in clinical settings. We aimed to
examine the effects of PPIs on well-being (primary outcome), depression, anxiety,
and stress (secondary outcomes) in clinical samples with psychiatric or somatic
disorders. METHODS: A systematic review and meta-analysis was conducted following
PRISMA guidelines. PsycINFO, PubMed, and Scopus were searched for controlled
studies of PPIs in clinical samples between Jan 1, 1998 and May 31, 2017.
Methodological quality of each study was rated. We used Hedges' adjusted g to
calculate effect sizes and pooled results using random-effect models. RESULTS:
Thirty studies were included, representing 1864 patients with clinical disorders.
At post-intervention, PPIs showed significant, small effect sizes for well-being
(Hedges' g = 0.24) and depression (g = 0.23) compared to control conditions when
omitting outliers. Significant moderate improvements were observed for anxiety (g
= 0.36). Effect sizes for stress were not significant. Follow-up effects (8-12
weeks), when available, yielded similar effect sizes. Quality of the studies was
low to moderate. CONCLUSION: These findings indicate that PPIs, wherein the focus
is on eliciting positive feelings, cognitions or behaviors, not only have the
potential to improve well-being, but can also reduce distress in populations with
clinical disorders. Given the growing interest for PPIs in clinical settings,
more high quality research is warranted as to determine the effectiveness of PPIs
in clinical samples. TRIAL REGISTRATION: PROSPERO CRD42016037451.
PMID- 29945604
TI - Who benefit from school doctors' health checks: a prospective study of a
screening method.
AB - BACKGROUND: School health services provide an excellent opportunity for the
detection and treatment of children at risk of later health problems. However,
the optimal use of school doctors' skills and expertise remains unknown.
Furthermore, no validated method for screening children for school doctors'
assessments exists. The aims of the study are 1) to evaluate the benefits or harm
of school doctors' routine health checks in primary school grades 1 and 5 (at
ages 7 and 11) and 2) to explore whether some of the school doctors' routine
health checks can be omitted using study questionnaires. METHODS: This is a
prospective, multicenter observational study conducted in four urban
municipalities in Southern Finland by comparing the need for a school doctor's
assessment to the benefit gained from it. We will recruit a random sample of 1050
children from 21 schools from primary school grades 1 and 5. Before the school
doctor's health check, parents, nurses and teachers fill a study questionnaire to
identify any potential concerns about each child. Doctors, blinded to the
questionnaire responses, complete an electronic report after the appointment,
including given instructions and follow-up plans. The child, parent, doctor and
researchers assess the benefit of the health check. The researchers compare the
need for a doctor's appointment to the benefit gained from it. At one year after
the health check, we will analyze the implementation of the doctors'
interventions and follow-up plans. DISCUSSION: The study will increase our
knowledge of the benefits of school doctors' routine health checks and assess the
developed screening method. We hypothesize that targeting the health checks to
the children in greatest need would increase the quality of school health
services. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03178331 , date
of registration June 6 th 2017.
PMID- 29945605
TI - A novel approach to identifying and quantifying neutrophil extracellular trap
formation in septic dogs using immunofluorescence microscopy.
AB - BACKGROUND: Canine neutrophils release neutrophil extracellular traps (NETs) in
response to lipopolysaccharide but NETs from clinical septic dogs had not been
identified. The primary aim is to describe the methodology of identifying and
quantifying neutrophil extracellular traps (NETs) in cytology samples of septic
foci in dogs with sepsis using immunofluorescence microscopy. Cytology samples
including endotracheal tracheal wash (ETW), bronchoalveolar lavage (BAL),
abdominal and pleural effusion collected from 5 dogs (3 septic, 2 non-septic)
were fixed, permeabilized and stained for myeloperoxidase (MPO), citrullinated
histone H3 (citH3) and cell-free DNA (cfDNA). Fluorescence microscopy was used to
identify and quantify NETs in 10 random views at 40* magnification. NETs were
identified based on co-localization of MPO, citH3 and cfDNA. NETs were quantified
as a ratio (number of NETs: number of neutrophils). Neutrophils were identified
based on cytoplasmic MPO, cellular diameter and nuclear morphology. RESULTS: NETs
were identified and quantified in all cytology samples collected from septic
dogs. A small number of NETs was documented in one dog with sterile chronic
bronchitis. No NETs were found in sterile abdominal effusion collected from one
dog with congestive heart failure. CONCLUSIONS: Immunofluorescence microscopy
could be a useful tool for the study of NETs in dogs with clinical sepsis.
PMID- 29945606
TI - Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis:
data from the UK National Chronic Rhinosinusitis Epidemiology Study.
AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a common disorder associated with
other respiratory tract diseases such as asthma and inhalant allergy. However,
the prevalence of these co-morbidities varies considerably in the existing
medical literature and by phenotype of CRS studied. The study objective was to
identify the prevalence of asthma, inhalant allergy and aspirin sensitivity in
CRS patients referred to secondary care and establish any differences between CRS
phenotypes. METHODS: All participants were diagnosed in secondary care according
to international guidelines and invited to complete a questionnaire including
details of co-morbidities and allergies. Data were analysed for differences
between controls and CRS participants and between phenotypes using chi-squared
tests. RESULTS: The final analysis included 1470 study participants: 221
controls, 553 CRS without nasal polyps (CRSsNPs), 651 CRS with nasal polyps
(CRSwNPs) and 45 allergic fungal rhinosinusitis (AFRS). The prevalence of asthma
was 9.95, 21.16, 46.9 and 73.3% respectively. The prevalence of self-reported
confirmed inhalant allergy was 13.1, 20.3, 31.0 and 33.3% respectively; house
dust mite allergy was significantly higher in CRSwNPs (16%) compared to CRSsNPs
(9%, p < 0.001). The prevalence of self- reported aspirin sensitivity was 2.26,
3.25, 9.61 and 40% respectively. The odds ratio for aspirin sensitivity amongst
those with AFRS was 28.8 (CIs 9.9, 83.8) p < 0.001. CONCLUSIONS: The prevalence
of asthma and allergy in CRS varies by phenoytype, with CRSwNPs and AFRS having a
stronger association with both. Aspirin sensitivity has a highly significant
association with AFRS. All of these comorbidities are significantly more
prevalent than in non-CRS controls and strengthen the need for a more
individualised approach to the combined airway.
PMID- 29945608
TI - Cornstarch is less allergenic than corn flour in dogs and cats previously
sensitized to corn.
AB - BACKGROUND: Corn appears to be an uncommon food source of allergens in dogs and
cats. There is limited information on the nature of the corn allergens in dogs
and cats and their presence in the various foodstuffs used in commercial pet
foods. The aim of this study was to determine if serum IgE from corn-sensitized
dogs and cats recognized proteins in corn flour and cornstarch, which are common
sources of carbohydrates in pet foods. RESULTS: We selected archived sera from
allergy-suspected dogs (40) and cats (40) with either undetectable, low, medium
or high serum levels of corn-specific IgE. These sera were tested then by ELISA
on plates coated with extracts made from corn kernels, corn flour, cornstarch and
the starch used in the commercially-available extensively-hydrolyzed pet food
Anallergenic (Royal Canin). Immunoblotting was then performed on the same
extracts with some of the sera from moderate-to-high corn-sensitized dogs and
cats. Using ELISA, it is mostly the dogs and cats with moderate and high corn
specific IgE levels that also had IgE identifying allergens in the flour (dogs:
20/30 sera, 67% - cats: 20/29, 69%). In contrast, none of the tested sera had
measurable IgE against proteins isolated from the cornstarch. Immunoblotting
confirmed the existence of numerous major corn allergens in the corn kernel
extract, fewer in that of the corn flour, while such allergens were not
detectable using this technique in the two cornstarch extracts. CONCLUSIONS: In
this study, ELISA and immunoblotting results suggest that IgE from corn
sensitized dogs are less likely to recognize allergens in cornstarch than in
kernel and flour extracts. As corn is not a common allergen source in dogs and
cats, and as its starch seems to be less allergenic than its flour, pet foods
containing cornstarch as a carbohydrate source are preferable for dogs and cats
suspected of suffering from corn allergy.
PMID- 29945607
TI - Molecular and cellular identification of the immune response in peripheral
ganglia following nerve injury.
AB - BACKGROUND: Neuroinflammation accompanies neural trauma and most neurological
diseases. Axotomy in the peripheral nervous system (PNS) leads to dramatic
changes in the injured neuron: the cell body expresses a distinct set of genes
known as regeneration-associated genes, the distal axonal segment degenerates and
its debris is cleared, and the axons in the proximal segment form growth cones
and extend neurites. These processes are orchestrated in part by immune and other
non-neuronal cells. Macrophages in ganglia play an integral role in supporting
regeneration. Here, we explore further the molecular and cellular components of
the injury-induced immune response within peripheral ganglia. METHODS: Adult male
wild-type (WT) and Ccr2 -/- mice were subjected to a unilateral transection of
the sciatic nerve and axotomy of the superior cervical ganglion (SCG). Antibody
arrays were used to determine the expression of chemokines and cytokines in the
dorsal root ganglion (DRG) and SCG. Flow cytometry and immunohistochemistry were
utilized to identify the cellular composition of the injury-induced immune
response within ganglia. RESULTS: Chemokine expression in the ganglia differed 48
h after nerve injury with a large increase in macrophage inflammatory protein
1gamma in the SCG but not in the DRG, while C-C class chemokine ligand 2 was
highly expressed in both ganglia. Differences between WT and Ccr2 -/- mice were
also observed with increased C-C class chemokine ligand 6/C10 expression in the
WT DRG compared to C-C class chemokine receptor 2 (CCR2)-/- DRG and increased
CXCL5 expression in CCR2-/- SCG compared to WT. Diminished macrophage
accumulation in the DRG and SCG of Ccr2 -/- mice was found compared to WT ganglia
7 days after nerve injury. Interestingly, neutrophils were found in the SCG but
not in the DRG. Cytokine expression, measured 7 days after injury, differed
between ganglion type and genotype. Macrophage activation was assayed by
colabeling ganglia with the anti-inflammatory marker CD206 and the macrophage
marker CD68, and an almost complete colocalization of the two markers was found
in both ganglia. CONCLUSIONS: This study demonstrates both molecular and cellular
differences in the nerve injury-induced immune response between DRG and SCG and
between WT and Ccr2 -/- mice.
PMID- 29945609
TI - Core knowledge translation competencies: a scoping review.
AB - BACKGROUND: Knowledge translation (KT) is the broad range of activities aimed at
supporting the use of research findings leading to evidence-based practice (EBP)
and policy. Recommendations have been made that capacity building efforts be
established to support individuals to enact KT. In this study, we summarized
existing knowledge on KT competencies to provide a foundation for such capacity
building efforts and to inform policy and research. Our research questions were
"What are the core KT competencies needed in the health sector?" and "What are
the interventions and strategies to teach and reinforce those competencies?"
METHODS: We used a scoping review approach and an integrated KT process by
involving an Advisory Group of diverse stakeholders. We searched seven health and
interdisciplinary electronic databases and grey literature sources for materials
published from 2003 to 2017 in English language only. Empirical and theoretical
publications in health that examined KT competencies were retrieved, reviewed,
and synthesized. RESULTS: Overall, 1171 publications were retrieved; 137 were
fully reviewed; and 15 empirical and six conceptual academic, and 52 grey
literature publications were included and synthesized in this scoping review.
From both the academic and grey literature, we categorized 19 KT core
competencies into knowledge, skills, or attitudes; and identified commonly used
interventions and strategies to enhance KT competencies such as education,
organizational support and hands-on training. CONCLUSIONS: These initial core KT
competencies for individuals provide implications for education, policy,
knowledge brokering, and future research, and on the need for future evaluation
of the KT competencies presented. We also discuss the essential role of
organizational support and culture for successful KT activities/practice.
PMID- 29945610
TI - Undeclared animal species in dry and wet novel and hydrolyzed protein diets for
dogs and cats detected by microarray analysis.
AB - BACKGROUND: Although the European Pet Food Industry Federation (FEDIAF) stated
that labels must be accurate and provide detailed information on the ingredients,
mislabeling of pet food has been documented by several authors. This phenomenon
is of particular concern when related to products used as elimination diets for
the diagnosis of adverse food reaction (AFR) in dogs and cats because the
presence of undeclared ingredients may negatively interfere with the trial and
prevent the veterinarian from making an appropriate diagnosis. The aim of this
study was to shed light upon the problem of contamination and mislabeling in both
dry and wet novel protein diets (NPDs) and hydrolyzed protein diets (HPDs) using
a microarray-based commercial kit which tests for the presence of 19 animal
species. RESULTS: Of the 40 analyzed products (9 dry NPDs, 22 wet NPDs, 6 dry
HPDs and 3 wet HPDs), ten presented a content that correctly matched the label,
while five did not contain the declared animal species, twenty-three revealed the
presence of undeclared animal species, and two had a vague label that did not
allow the evaluation of its accuracy. The most frequently contaminants identified
in both dry and wet pet foods were pork, chicken and turkey. The presence of
undeclared animal species was higher in dry than wet pet foods; furthermore, a
lower number of contaminating animal species was identified in HPDs than NPDs (4
vs 10), and a lower number of contaminated HPDs (6 out of 9, 67%) than
contaminated NPDs was detected (24 out of 31, 77%). Thirteen out of 14 brands
tested presented at least one mislabeled product. CONCLUSIONS: Mislabeling seems
to be a widespread issue in pet foods used as elimination diets. Contamination
can occur in all types of products used for the purpose, although dry NPDs are
the main issue. Due to the high risk of contamination, particular attention
should be given to both the selection of raw material suppliers and the
production process.
PMID- 29945612
TI - Assessing the policy and practice impact of an international policy initiative:
the State of the World's Midwifery 2014.
AB - BACKGROUND: Understanding how policies lead to changes in health systems and in
practice helps policymakers and researchers to intervene more successfully. Yet
identifying all the possible changes that occur as a result of a new policy is
challenging not only methodologically and logistically, as limited resources are
available to conduct indefinite evaluations, but also theoretically, as a
complete mapping and attribution of post-hoc changes requires a full
understanding of the mechanisms underpinning all change. One option is to
identify possible changes across a number of policy impact domains. METHODS:
Using a Policy Impact Framework, we brought together data from media, documents
and interviews to identify changes to midwifery policy, practice and provision,
following the launch of a new global policy initiative, the State of the World's
Midwifery (SoWMy 2014) report published in 2014. We used these identified impacts
to develop a map of the mechanisms underpinning these changes. RESULTS: SoWMy
2014 contributed to a number of changes at national levels, including increased
status of midwifery within national governments, improved curricula and training
opportunities for midwives, and improved provision of and access to midwifery-led
care. These contributions were attributed to SoWMy 2014 via mechanisms such as
stakeholder interaction and acquisition of government support, holding national
and international dissemination and training events, and a perceived global
momentum around supporting midwifery provision. Policy initiatives of this kind
can lead to changes in national and international policy dialogue and practice.
We identify factors and mechanisms that are likely to increase the scope and
scale of these changes, at contextual, national and global levels. CONCLUSIONS:
Identifying changes following a policy using a policy impact framework can help
researchers and policymakers understand why policies have the effect they do.
This is important information for those wishing to increase the effectiveness of
future policies and interventions.
PMID- 29945611
TI - Altering cortical input unmasks synaptic phenotypes in the YAC128 cortico
striatal co-culture model of Huntington disease.
AB - BACKGROUND: Huntington disease (HD) is a fatal neurodegenerative disorder caused
by a CAG expansion in the huntingtin (HTT) gene, leading to selective and
progressive neuronal death predominantly in the striatum. Mutant HTT expression
causes dysfunctional cortico-striatal (CS) transmission, loss of CS synapses, and
striatal medium spiny neuron (MSN) dendritic spine instability prior to neuronal
death. Co-culturing cortical and striatal neurons in vitro promotes the formation
of functional CS synapses and is a widely used approach to elucidate pathogenic
mechanisms of HD and to validate potential synapto-protective therapies. A number
of relevant in vivo synaptic phenotypes from the YAC128 HD mouse model, which
expresses full-length transgenic human mutant HTT, are recapitulated in CS co
culture by 21 days in vitro (DIV). However, striatal spine loss, which occurs in
HD patients and in vivo animal models, has been observed in YAC128 CS co-culture
in some studies but not in others, leading to difficulties in reproducing and
interpreting results. Here, we investigated whether differences in the relative
proportion of cortical and striatal neurons alter YAC128 synaptic phenotypes in
this model. RESULTS: YAC128 MSNs in 1:1 CS co-culture exhibited impaired
dendritic length and complexity compared to wild-type, whereas reducing cortical
input using a 1:3 CS ratio revealed a dramatic loss of YAC128 MSN dendritic
spines. Chimeric experiments determined that this spine instability was primarily
cell autonomous, depending largely on mutant HTT expression in striatal neurons.
Moreover, we found that spontaneous electrophysiological MSN activity correlated
closely with overall dendritic length, with no differences observed between
genotypes in 1:3 co-cultures despite significant YAC128 spine loss. Finally,
limiting cortical input with a 1:3 CS ratio impaired the basal survival of YAC128
neurons at DIV21, and this was partially selective for dopamine- and cAMP
regulated phosphoprotein 32-positive MSNs. CONCLUSIONS: Our findings reconcile
previous discordant reports of spine loss in this model, and improve the utility
and reliability of the CS co-culture for the development of novel therapeutic
strategies for HD.
PMID- 29945613
TI - Barriers and facilitators to using a web-based tool for diagnosis and monitoring
of patients with depression: a qualitative study among Danish general
practitioners.
AB - BACKGROUND: Depression constitutes a significant part of the global burden of
diseases. General practice plays a central role in diagnosing and monitoring
depression. A telemedicine solution comprising a web-based psychometric tool may
reduce number of visits to general practice and increase patient empowerment.
However, the current use of telemedicine solutions in the field of general
practice is limited. This study aims to explore barriers and facilitators to
using a web-based version of the Major Depression Inventory (eMDI) for
psychometric testing of potentially depressive patients in general practice.
METHODS: Semi-structured individual interviews were conducted with nine general
practitioners (GPs) from eight general practices in the Central Denmark Region.
All interviewees had previous experience in using the eMDI in general practice.
Determinants for using the eMDI were identified in relation to the GPs'
capability, opportunity and motivation to change clinical behaviour (the COM-B
system). RESULTS: Our results indicate that the main barriers for using the eMDI
are related to limitations in the GPs' opportunity in regards to having the time
it takes to introduce change. Further, the use of the eMDI seems to be hampered
by the time-consuming login process. Facilitating factors included behavioural
aspects of capability, opportunity and motivation. The implementation of the eMDI
was facilitated by the interviewees' previous familiarity with the paper-based
version of the tool. Continued use of the eMDI was facilitated by a time-saving
documentation process and motivational factors associated with clinical core
values. These factors included perceptions of improved consultation quality and
services for patients, improved possibilities for GPs to prioritise their
patients and improved possibilities for disease monitoring. Furthermore, the
flexible nature of the eMDI allowed the GPs to use the paper-based MDI for
patients whom the eMDI was not considered appropriate. CONCLUSIONS:
Implementation of a telemedicine intervention in general practice can be
facilitated by resemblance between the intervention and already existing tools as
well as the perception among GPs that the intervention is time-saving and
improves quality of care for the patients.
PMID- 29945614
TI - Quantitative evaluation of binary digital region asymmetry with application to
skin lesion detection.
AB - BACKGROUND: The performance of Computer Aided Diagnosis Systems for early
melanoma detection relies mainly on quantitative evaluation of the geometric
features corresponding to skin lesions. In these systems, diagnosis is carried
out by analyzing four geometric characteristics: asymmetry (A), border (B), color
(C) and dimension (D). The main objective of this study is to establish an
algorithm for the measurement of asymmetry in biological entities. METHODS:
Binary digital images corresponding to lesions are divided into 8 segments from
their centroid. For each segment, the discrete compactness value is calculated
using Normalized E-Factor (NEF). The asymmetry value is obtained from the sum of
the square difference of each NEF value and corresponding value of its opposite
by the vertex. Two public skin cancer databases were used. 1) Lee's database with
40 digital regions evaluated by fourteen dermatologists. 2) The PH2 database
which consists of 200 images in an 8-bit RGB format. This database provides a pre
classification of asymmetry carried out by experts, and it also indicates if the
lesion is a melanoma. RESULTS: The measure was applied using two skin lesion
image databases. 1) In Lee's database, Spearman test provided a value of 0.82
between diagnosis of dermatologists and asymmetry values. For the 12 binary
images most likely to be melanoma, the correlation between the measurement and
dermatologists was 0.98. 2) In the PH2 database a label is provided for each
binary image where the type of asymmetry is indicated. Class 0-1 corresponds to
symmetry and one axis of symmetry shapes, the completely asymmetrical were
assigned to Class 2, the values of sensitivity and specificity were 59.62 and
85.8% respectively between the asymmetry measured by a group of dermatologists
and the proposed algorithm. CONCLUSIONS: Simple image digital features such as
compactness can be used to quantify the asymmetry of a skin lesion using its
digital binary image representation. This measure is stable taking into account
translations, rotations, scale changes and can be applied to non-convex regions,
including areas with holes.
PMID- 29945615
TI - The draft genomes and investigation of serotype distribution, antimicrobial
resistance of group B Streptococcus strains isolated from urine in Suzhou, China.
AB - BACKGROUND: The group B Streptococcus (GBS) is a human commensal bacterium, which
is capable of causing several infectious diseases in infants, and people with
chronic diseases. GBS has been the most common cause of infections in urinary
tract of the elders, but relatively few studies reported the urine-isolated GBS
and their antimicrobial susceptibilities. Hence, we decided to investigate GBS
specially isolated from urine in Suzhou, China. METHODS: 27 GBS samples were
isolated from urine in Suzhou, China. The PCR and agarose gel electrophoresis
were used to identify the serotype distribution. Susceptibility tests were based
on MIC test and Kirby-Bauer test. Genome were sequenced via Illumina Hiseq
platform and assembled by SPAdes. Genomes of five isolates were sequenced and
submitted to NCBI genome database. The sequencing files in fastq format were
submitted to NCBI SRA database. RESULTS: Five serotypes were identified. The
resistant rates measured for tetracycline, erythromycin, clindamycin and
fluoroquinolones were 74.1, 63.0, 44.4 and 48.1%, respectively. 18.5% of the
isolates were nonsusceptible to nitrofurantoin. The resistance to tetracycline
was mainly associated with the gene tetM. The erythromycin resistance was mainly
associated with the genes ermB and mefE. The genes ermB and lnuB were the
prevalent genes in cMLSB type. No known nitrofurantoin resistance gene was found
in nitrofurantoin-nonsusceptible GBS. CONCLUSIONS: Five serotypes were identified
in our study. High rates of GBS isolates were resistant to tetracycline,
erythromycin, clindamycin and fluoroquinolones. The genes ermB and lnuB occupied
high rates in cMLSB phenotype.
PMID- 29945616
TI - Migration motives and integration of international human resources of health in
the United Kingdom: systematic review and meta-synthesis of qualitative studies
using framework analysis.
AB - OBJECTIVE: The aim of this review was to examine the migration motives, the
barriers to and facilitators of integration of international dental graduates,
compared with nurses and doctors in the United Kingdom. METHODS: Electronic
databases Ovid MEDLINE, EMBASE, PubMed, Web of Knowledge and OECD publications
were systematically searched for English language publications from January 2000
to January 2017. A total of 31 qualitative studies were selected and quality
appraised and meta-synthesis of the qualitative data was carried out using
framework synthesis. The Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) guidelines were applied to present the findings. RESULTS:
There were no studies on migration motives and one study on integration
experiences of international dentists in the UK. The nursing literature had the
highest volume and quality of evidence on nursing workforce, whilst there was
limited literature on international doctors in the UK. Migration of health
professionals to the UK is determined by personal and professional factors,
together with source country-specific and UK drivers. Active recruitment, post
graduate training and financial gain act as strong common macro, meso and micro
drivers that perpetuate migration into the UK, but the extent to which each of
these drivers influence nurses' and doctors' migration is different. Integration
experiences for international nurses and doctors differed based on their source
country experiences and the work environment they entered. Nurses reported a
wider knowledge and skills gap, more multi-level discrimination and less career
progression compared to the doctors. The migrants' integration experiences depend
on their cultural awareness, discrimination exposure, English language and
communication skills, social and professional support networks, social
integration and personal attributes. CONCLUSION: Migration of international
health professionals is motivated by macro, meso and micro drivers at the
international, national, professional and personal levels. The UK has strong
common macro pull factors which attract nurses, doctors and dentists and may
impact on the effectiveness of policies to restrict their migration. The
integration experiences of nurses and doctors differ and further research is
required to understand the integration experiences of dentists, in order to
retain these professionals by tailoring policies to each of these professions.
PMID- 29945618
TI - Stunning of common carp: Results from a field and a laboratory study.
AB - BACKGROUND: Common carp Cyprinus carpio is an important food fish in Central
Europe, which in some regions is consumed as part of local tradition. The
majority of carp are sold by small retailers and not processed in commercial
processing plants. The overall objective of this study was to monitor how animal
welfare is safeguarded during the stunning and slaughtering of carp for retail
sale. For this, the stunning and slaughtering process was monitored on 12 carp
farms. Four welfare-related parameters were assessed: (i) stunning success, (ii)
injuries related to the applied stunning method, (iii) time between stunning and
slaughter, and (iv) visible responses of carp during slaughtering. In addition,
indicators of physiological stress were measured. In order to analyse whether the
absence of behavioural indicators of consciousness after electrical stunning was
correlated with unconsciousness a complementary laboratory study was performed.
Here, carp were exposed to electrical current densities between 0.09 and 0.41
A/dm2. The presence of behavioural responses and visually-evoked responses (VER)
in the electro-encephalogram in response to light flashes as indicators for an
absence of consciousness was recorded. RESULTS: The carp farms applied manual
percussive (18%) or electrical (23%) stunning methods, while the majority of
farms used a combination of electrical stunning immediately followed by manual
percussive stunning (59%). In the latter condition, 92.6% of stunned carp
displayed no behavioural indicators of consciousness and significantly fewer
injuries related to mishits compared to sole percussive stunning. In the
laboratory study, behavioural indicators of consciousness recovered in carp
between 1 and 9 min following removal of the electrical current. However, VER
could be recorded already at 30 +/- 8 s post stunning. This indicates a fast
recovery of carp from electrical stunning when exposed to current densities in
the range of those generated by commercially available stunning instruments for
fish. CONCLUSIONS: Under field conditions, percussion (applied manually) and
electrical stunning might be poor inducers of unconsciousness before slaughter,
while a combination was most effective. In order to undertake improvements in
electrical stunning, further investigations into the current density, required
for inducing prolonged insensibility in carp during electrical stunning, are
needed.
PMID- 29945617
TI - Prospective plasma lipid profiling in individuals with and without depression.
AB - BACKGROUND: So far, studies on possible association of plasma lipid levels and
depressive disorder are contradictory. This prospective work aimed at assessing a
plasma lipid profile in individuals with major depression and healthy controls.
METHODS: In total, 94 patients with major depression and 152 healthy controls
were included in this prospective study. After an overnight fasting state of 12 h
they underwent blood drawing for triglyzerides (TG), total cholesterol, low
density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol
measurements. All participants were evaluated in a clinical interview and filled
out the self-rating Beck Depression Inventory (BDI-II) scale to identify
depressive symptomatology. RESULTS: Ninety-four patients with major depression
showed significantly higher median (interquartile range) plasma TG levels (108.0
[75.8-154.1] vs. 84.0 [63.0-132.2] mg/dL, P = 0.014) and significantly lower HDL
cholesterol levels (55.0 [46.9-123.0] vs. 61.5 [47.4-72.6] mg/dL, P = 0.049)
compared to 152 individuals without depression, respectively. Total and LDL
cholesterol concentrations were observed slightly higher in patients with major
depression. Significant positive correlation was found between TG, total
cholesterol and LDL-cholesterol concentrations and the BDI-II score (p = 0.027,
0.048 and 0.018), and in tendency negative correlation between HDL-cholesterol
levels and the BDI-II score (P = 0.091), respectively. CONCLUSIONS: Depressive
individuals were found with adverse plasma lipid patterns of higher TG and lower
HDL-cholesterol levels compared to healthy controls. On this basis, the authors
would suggest the implementation of routine lipid measurements in order to
stratify these patients by their cardiovascular risk.
PMID- 29945619
TI - Quantifying spatial accessibility in public health practice and research: an
application to on-premise alcohol outlets, United States, 2013.
AB - OBJECTIVE: To assess spatial accessibility measures to on-premise alcohol outlets
at census block, census tract, county, and state levels for the United States.
METHODS: Using network analysis in a geographic information system, we computed
distance-based measures (Euclidean distance, driving distance, and driving time)
to on-premise alcohol outlets for the entire U.S. at the census block level. We
then calculated spatial access-based measures, specifically a population-weighted
spatial accessibility index and population-weighted distances (Euclidean
distance, driving distance, and driving time) to alcohol outlets at the census
tract, county, and state levels. A multilevel model-based sensitivity analysis
was conducted to evaluate the associations between different on-premise alcohol
outlet accessibility measures and excessive drinking outcomes. RESULTS: The
national average population-weighted driving time to the nearest 7 on-premise
alcohol outlets was 5.89 min, and the average population-weighted driving
distance was 2.63 miles. At the state level, population-weighted driving times
ranged from 1.67 min (DC) to 15.29 min (Arizona). Population-weighted driving
distances ranged from 0.67 miles (DC) to 7.91 miles (Arkansas). At the county
level, population-weighted driving times and distances exhibited significant
geographic variations, and averages for both measures increased by the degree of
county rurality. The population-weighted spatial accessibility indexes were
highly correlated to respective population-weighted distance measures.
Sensitivity analysis demonstrated that population weighted accessibility measures
were more sensitive to excessive drinking outcomes than were population weighted
distance measures. CONCLUSIONS: These results can be used to assess the
relationship between geographic access to on-premise alcohol outlets and health
outcomes. This study demonstrates a flexible and robust method that can be
applied or modified to quantify spatial accessibility to public resources such as
healthy food stores, medical care providers, and parks and greenspaces, as well
as, quantify spatial exposure to local adverse environments such as tobacco
stores and fast food restaurants.
PMID- 29945620
TI - Synaptopathy, circuitopathy and the computational biology of Huntington's
disease.
AB - Huntington's disease (HD) is one of the most common tandem repeat disorders and
presents as a unique trilogy of cognitive, psychiatric and motor symptoms. One of
the major mysteries of HD is why it selectively affects specific neuronal
populations. A new article in BMC Biology provides a piece in the puzzle of
pathogenesis. By demonstrating the delicate relationship between cortical and
striatal neurons, it provokes broader questions of how we might understand HD as
a disorder of synapses, neural circuits and systems biology.
PMID- 29945621
TI - Ethical issues related to human papillomavirus vaccination programs: an example
from Bangladesh.
AB - BACKGROUND: Human Papilloma Virus (HPV) vaccine was introduced in Bangladesh
through the arrangement of a demonstration project in Gazipur district in 2016,
targeting grade five female students and non-school going girls (age range 10-12
years). HPV vaccination is expected to be eventually included in the nationwide
immunization program if the demonstration project is successful. However,
introduction and implementation of such a vaccination program raises various
ethical concerns. This review paper illustrates a step by step assessment of the
ethical concerns surrounding the HPV vaccination implementation in Bangladesh
considering specific elements in administering and conducting the program as well
as the intended results. Policy-makers, vaccine implementers, vaccine recipients,
and an ethics specialist in Bangladesh were interviewed. Electronic database and
websites have also been reviewed for relevant published literature and government
statements. This program imparted inadequate knowledge about HPV and cervical
cancer to the recipients and participants. There was lack of autonomous and
informed choice of the girls and their parents about taking the vaccine. The
program did not have any follow-up plan for the adverse effects in the long run.
The impact of a female-only strategy in the larger societal context was
overlooked. There was lack of awareness among the implementers about safeguarding
the ethical issues pertaining to HPV vaccination. CONCLUSION: Adolescent health
education imparted in the scope of the vaccination program should contain
adequate information about HPV, its mode of transmission, risk factors along with
the importance of secondary prevention despite primary prevention. Adolescent
boys should be given HPV related health education as well. The right of making
informed choice should be appreciated and respected. More ethical discussion and
debate should be done among the public health professionals of Bangladesh in
order to increase awareness about ethical issues related to human health.
PMID- 29945622
TI - Hospital length of stay variation and comorbidity of mental illness: a
retrospective study of five common chronic medical conditions.
AB - BACKGROUND: With the increasing burden of mental illness globally, it is becoming
common for hospitalised patients with chronic medical conditions to have a
comorbidity of mental illness. This combination could prolong length of stay
(LOS) of this patient cohort. We conducted an investigation in Tasmania,
Australian hospitals to characterise this cohort and assess if co-morbidity of
mental illness is a distinguishing factor that generates LOS variation across
different chronic medical conditions. METHODS: The retrospective study analysed
16,898 admissions of patients with a primary diagnosis of one of five chronic
medical conditions: lung or colorectal cancer, chronic obstructive pulmonary
disease (COPD), type II diabetes, ischaemic heart disease (IHD) and stroke. Data
were from July 2010 to June 2015, across four hospitals that collectively cover
95% of public hospital admissions in Tasmania, Australia. Descriptive statistics
were used to compare characteristics of patients between the scenarios of with
and without co-morbidity of mental illness. We used negative binomial regression
models to assess whether co-morbidity of mental illness, along with its sub
types, after adjustment for potential confounding variables, associated with LOS
variation in patients of each medical condition. Based on the adjusted LOS
variation, we estimated differences in bed days' use between patients with and
without comorbidity of mental illness. RESULTS: Patients with co-morbidity of
mental illness were significantly younger in comparison to patients without
mental illness. With each medical condition, patients with comorbidity of mental
illness had incurred higher bed days' use than for those without mental illness.
In cancer and stroke cohorts, co-morbidity of mental illness unfavourably
affected the LOS variation by as high as 97% (CI: 49.9%-159%) and 109% (78%
146%), respectively. Though mental and behavioural disorders due to psychoactive
substances was a dominant sub-type of mental illness across the medical
conditions, it contributed significant unfavourable LOS variation only in the
stroke patients i.e. 36.3% (CI: 16.2%-59.9%). CONCLUSIONS: Mental illness
consistently produced unfavourable LOS variation. Upskilling of healthcare teams
and greater reporting and analysis of LOS variation for this patient cohort, and
the sub-cohorts within it, are necessary to provide improved medical care and
achieve system efficiencies.
PMID- 29945623
TI - Integrated primary health care in low- and middle-income countries: a double
challenge.
AB - BACKGROUND: The lack of primary healthcare integration has been identified as one
of the main limits to programs' efficacy in low- and middle-income countries.
This is especially relevant to the Millennium Development Goals, whose health
objectives were not attained in many countries at their term in 2015. While
global health scholars and decision-makers are unanimous in calling for
integration, the objective here is to go further and contribute to its promotion
by presenting two of the most important challenges to be met for its achievement:
1) developing a "crosswise approach" to implementation that is operational and
effective; and 2) creating synergy between national programs and interventions
driven by non-State actors. MAIN BODY: The argument for urgently addressing this
double challenge is illustrated by drawing on observations made and lessons
learned during a four-year research project (2011-2014) evaluating the effects of
interventions against malaria in Burkina Faso. The way interventions were framed
was mostly vertical, leaving little room for local adaptation. In addition, many
non-governmental organizations intervened and contributed to a fragmented and
heteronomous health governance system. Important ethical issues stem from how
interventions against malaria were shaped and implemented in Burkina Faso. To
further explore this issue, a scoping literature review was conducted in August
2016 on the theme of integrated primary healthcare. It revealed that no clear
definition of the concept has been advanced or endorsed thus far. We call for
caution in conceptualizing it as a simple juxtaposition of different tasks or
missions at the primary care level. It is time to go beyond the debate around
selective versus comprehensive approaches or fragmentation versus cohesion.
Integration should be thought of as a process to reconcile these tensions.
CONCLUSIONS: In the context that characterizes many low- and middle-income
countries today, better aid coordination and public health systems strengthening,
as promoted by multisectoral approaches, might be among the best options to
sustainably and ethically integrate primary healthcare interventions.
PMID- 29945624
TI - Comparing tariff and medical assistant assigned causes of death from verbal
autopsy interviews in Matlab, Bangladesh: implications for a health and
demographic surveillance system.
AB - BACKGROUND: Deaths in developing countries often occur outside health facilities,
making it extremely difficult to gather reliable cause of death (COD)
information. Automated COD assignment using a verbal autopsy instrument (VAI) has
been proposed as a reliable and cost-effective alternative to traditional
physician-certified verbal autopsy, but its performance is still being evaluated.
The purpose of this study was to compare the similarity of diagnosis by Medical
Assistants (MA) in the Matlab Health and Demographic Surveillance System (HDSS)
with the SmartVA Analyze 1.2 (Tariff 2.0) diagnosis. METHODS: This study took
place between January 2011 and April 2014 in Matlab, Bangladesh. MA with 3 years
of medical training assigned COD to Matlab residents by reviewing the information
collected using the Population Health Metrics Research Consortium (PHMRC) long
form VAI. Smart VA Analyze 1.2 automatically assigned COD using the same
questionnaire. COD agreement and cause-specific mortality fractions (CSMFs) were
compared for MA and Tariff. RESULTS: Of the 4969 verbal autopsy cases reviewed,
4328 were adults, 296 were children, and 345 were neonates. Cohen's kappa was
0.38 (0.36, 0.40) for adults, 0.43 (0.38, 0.49) for children, and 0.27 (0.22,
0.33) for neonates. For adults, the top two COD for MA were stroke (29.6%) and
ischemic heart diseases (IHD) (14.2%) and for Tariff these were stroke (32.0%)
and IHD (14.0%). For children, the top two COD for MA were drowning (33.5%) and
pneumonia (13.2%) and for Tariff these were also drowning (36.8%) and pneumonia
(12.4%). For neonates, the top two COD for MA were birth asphyxia (41.2%) and
meningitis/sepsis (22.3%) and for Tariff these were birth asphyxia (37.0%) and
preterm delivery (30.9%). CONCLUSION: The CSMFs for Tariff and MA showed very
close agreement across all age categories but some differences were observed for
neonate preterm delivery and meningitis/sepsis. Given the known advantages of
automated methods over physician certified verbal autopsy, the SmartVA software,
incorporating the shortened VAI questionnaire and Tariff 2.0, could serve as a
cost-effective alternative to Matlab MA to routinely collect and analyze verbal
autopsy data in a HDSS to generate essential population level COD data for
planning.
PMID- 29945625
TI - Eight weeks of resistance training in conjunction with glutathione and L
Citrulline supplementation increases lean mass and has no adverse effects on
blood clinical safety markers in resistance-trained males.
AB - BACKGROUND: Supplementation of combined glutathione (GSH) with L-citrulline in
response to a single bout of resistance exercise has been shown to increase
plasma nitric oxide metabolites, nitrite and nitrate and cyclic guanosine
monophosphate (cGMP), which may play a role in muscle protein synthesis. As a
result, in response to resistance training (RT) these responses may establish a
role for GSH + L-citrulline to increase muscle mass. This study attempted to
determine the effects of an 8-week RT program in conjunction with GSH (Setria(r))
+ L-citrulline, L-citrulline-malate, or placebo supplementation on lean mass and
its association with muscle strength. The secondary purpose was to assess the
safety of such supplementation protocol by assessing clinical chemistry markers.
METHODS: In a randomized, double-blind, placebo-controlled design, 75 resistance
trained males were randomly assigned to ingest GSH + L-citrulline (GSH + CIT), L
citrulline-malate, or cellulose placebo daily while also participating in 8 weeks
of RT. The full dose of each supplement was delivered in capsules that were
identical in weight, size, shape, and color. Participants completed testing
sessions for body composition and muscle strength before and after 4 and 8 weeks
of RT and supplementation. Venous blood samples were obtained before and after 8
weeks. RESULTS: Leg press was increased with RT but was not significantly
different between groups (p > 0.05); however, bench press strength was not
increased with RT (p > 0.05). There were no significant changes in total body
mass, fat mass, or total body water during 8 weeks of RT and supplementation.
Lean mass increased in both GSH + CIT when compared to PLC; however, the increase
was significant only after 4 weeks. Lean mass and strength were positively
correlated (p < 0.05) in GSH + CIT, but not CIT-malate or PLC. Neither RT nor
supplementation had any significant effects on blood clinical chemistry variables
(p > 0.05). CONCLUSION: Compared to PLC, supplementation of GSH + CIT during
resistance training increased lean mass after 4 weeks of RT and was positively
associated with muscle strength. However, after 8 weeks of RT there were no
significant differences in any of the measured variables.
PMID- 29945626
TI - Abdominal subcutaneous adipose tissue: a favorable adipose depot for diabetes?
AB - BACKGROUND: Previous studies have documented that visceral adipose tissue is
positively associated with the risk of diabetes. However, the association of
subcutaneous adipose tissue with diabetes risk is still in dispute. We aimed to
assess the associations between different adipose distributions and the risk of
newly diagnosed diabetes in Chinese adults. METHODS: The Shanghai Nicheng Cohort
Study was conducted among Chinese adults aged 45-70 years. The baseline data of
12,137 participants were analyzed. Subcutaneous and visceral fat area (SFA and
VFA) were measured by magnetic resonance imaging. Diabetes was newly diagnosed
using a 75 g oral glucose tolerance test. RESULTS: The multivariable-adjusted
odds ratios (OR) and 95% confidence intervals (CI) of newly diagnosed diabetes
per 1-standard deviation increase in SFA and VFA were 1.29 (1.19-1.39) and 1.61
(1.49-1.74) in men, and 1.10 (1.03-1.18) and 1.56 (1.45-1.67) in women,
respectively. However, the association between SFA and newly diagnosed diabetes
disappeared in men and was reversed in women (OR 0.86 [95% CI, 0.78-0.94]) after
additional adjustment for body mass index (BMI) and VFA. The positive association
between VFA and newly diagnosed diabetes remained significant in both sexes after
further adjustment for BMI and SFA. Areas under the receiver operating
characteristic curve of newly diagnosed diabetes predicted by VFA (0.679 [95% CI,
0.659-0.699] for men and 0.707 [95% CI, 0.690-0.723] for women) were
significantly larger than by the other adiposity indicators. CONCLUSIONS: SFA was
beneficial for lower risk of newly diagnosed diabetes in women but was not
associated with newly diagnosed diabetes in men after taking general obesity and
visceral obesity into account. VFA, however, was associated with likelihood of
newly diagnosed diabetes in both Chinese men and women.
PMID- 29945627
TI - Dyslipidaemia was correlated to the posterior circulation infarction in non
diabetic populations.
AB - BACKGROUND: Diabetes mellitus (DM) was prone to happening in posterior
circulation infarction (POCI) and DM also has the impact on the lipids, our study
was to investigate the correlation between lipid compositions and POCI. METHODS:
Data was collected from the patients with acute ischemic stroke (AIS)
hospitalization in Affiliated Drum Tower Hospital of Nanjing University Medical
School from October 2008 to May 2012. Lipids and other risk factors in the
different populations were investigated in relation to occurrence of POCI based
on the infarction location. RESULTS: Six hundred ten patients with AIS were
included in this study, which had 428 with anterior circulation infarction (ACI)
and 182 with POCI. Elevated Triglyceride (TG) and decreased High density
lipoprotein cholesterol (HDL-C) were seen in the POCI of total populations and
AIS without DM compared to the ACI, but not in the populations of AIS with DM, so
did the elevated TG/HDL-C ratios. Also, the percent of low HDL-C level and high
TG level were higher in POCI group than that in ACI group. Furthermore, single
factors logistic regression demonstrated that TG, HDL-C and TG/HDL-C ratio were
correlated to the POCI whatever in the total populations or AIS without DM, but
this kind of trend just maintained in the populations of AIS without DM after
adjusting by relative interference factors. CONCLUSION: Dyslipidaemia was prone
to happening in POCI compared to ACI in the non-diabetic populations, which was
correlated to the pathogenesis of POCI.
PMID- 29945628
TI - Improving pregnancy outcomes in low- and middle-income countries.
AB - This paper reviews the very large discrepancies in pregnancy outcomes between
high, low and middle-income countries and then presents the medical causes of
maternal mortality, stillbirth and neonatal mortality in low-and middle-income
countries. Next, we explore the medical interventions that were associated with
the very rapid and very large declines in maternal, fetal and neonatal mortality
rates in the last eight decades in high-income countries. The medical
interventions likely to achieve similar declines in pregnancy-related mortality
in low-income countries are considered. Finally, the quality of providers and the
data to be collected necessary to achieve these reductions are discussed. It is
emphasized that single interventions are unlikely to achieve important reductions
in pregnancy-related mortality. Instead, improving the overall quality of
pregnancy-related care across the health-care system will be necessary. The
conditions that cause maternal mortality also cause stillbirths and neonatal
deaths. Focusing on all three mortalities together is likely to have a larger
impact than focusing on one of the mortalities alone.
PMID- 29945629
TI - Translating research evidence into practice: a report from the 2nd International
Conference on Maternal and Newborn Health from KLE University - Belagavi, India.
AB - The Jawaharlal Nehru Medical College (JNMC) Women's and Children's Health
Research Unit (WCHRU) of the Karnataka Lingayat Education (KLE) Academy of Higher
Education and Research Deemed-to-be-University and its collaborators convened the
'2nd International Conference on Maternal and Newborn Health -Translating
Research Evidence to Practice' to address the common theme of improving maternal
and newborn health in low- and middle- income countries (LMIC). This supplement,
including 16 manuscripts, reflects much of the research presented at the
conference, including analyses of the state of knowledge, as well as completed,
ongoing and planned research in these areas conducted by the WCHRU in India
together with many collaborators across high-income and LMIC. The first paper
reviews maternal, fetal and neonatal mortality in low-income countries, considers
their causes, as well as evidence for potential interventions to reduce
mortality. A second paper addresses near miss maternal mortality. Several
manuscripts address the research conducted by WCHRU and their colleagues in a
multi-center research network. One study examines rates of miscarriage and
medically terminated pregnancy in India and the risk factors for these
occurrences. Another paper addresses stillbirth and its risk factors, both in
India as well as in other LMIC. Haemorrhage and preeclampsia/eclampsia, important
causes of maternal mortality, stillbirth and neonatal morbidity in LMIC, are
addressed in a series of papers summarizing trials of interventions to reduce
improve outcomes associated with these conditions. Poor maternal and infant
nutritional status, which contribute to adverse outcomes, are addressed through
papers which describe a number of important studies that the WCHRU and their
colleagues have conducted to attempt to improve nutritional status. Another paper
describes a study to investigate causes of stillbirth and deaths among preterm
births, which will utilize new techniques to investigate the infectious causes of
these deaths. Finally, the supplement addresses the process for dissemination of
research results to inform public policy. Together these manuscripts represent a
body of research to inform interventions to reduce maternal, fetal and newborn
mortality and illustrates what a dedicated research group together with
institutional support can accomplish.
PMID- 29945630
TI - The impact of service and hearing dogs on health-related quality of life and
activity level: a Swedish longitudinal intervention study.
AB - BACKGROUND: Individuals with severe disability often require personal assistance
and help from informal caregivers, in addition to conventional health care. The
utilization of assistance dogs may decrease the need for health and social care
and increase the independence of these individuals. Service and hearing dogs are
trained to assist specific individuals and can be specialized to meet individual
needs. The aim of this study was to describe and explore potential consequences
for health-related quality of life, well-being and activity level, of having a
certified service or hearing dog. METHODS: A longitudinal interventional study
with a pre-post design was conducted. At inclusion, all participants in the study
had a regular (untrained) companion dog. Data were collected before training of
the dog started and three months after certification of the dog. Health-related
quality of life was assessed with EQ-5D-3L, EQ-VAS and RAND-36. Well-being was
measured with WHO-5 and self-esteem with the Rosenberg Self-Esteem Scale. In
addition, questions were asked about physical activity and time spent away from
home and on social activities. Subgroups were analyzed for physical service and
diabetes alert dogs. RESULTS: Fifty-five owner-and-dog pairs completed the study
(30 physical service dogs, 20 diabetes alert dogs, 2 epilepsy alert dogs, and 3
hearing dogs). Initially, study participants reported low health-related quality
of life compared with the general population. At follow-up, health-related
quality of life measured with the EQ-VAS, well-being and level of physical
activity had improved significantly. In the subgroup analysis, physical service
dog owners had lower health-related quality of life than diabetes alert dog
owners. The improvement from baseline to follow-up measured with EQ-5D
statistically differed between the subgroups. CONCLUSIONS: The target population
for service and hearing dogs has an overall low health-related quality of life.
Our study indicates that having a certified service or hearing dog may have
positive impact on health-related quality of life, well-being and activity level.
Service and hearing dogs are a potentially important "wagging tail aid" for this
vulnerable population, able to alleviate strain, increase independence, and
decrease the risk of social isolation. TRIAL REGISTRATION: The trial was
retrospectively registered in http://clinicaltrial.gov , NCT03270592. September,
2017.
PMID- 29945631
TI - Specifying sickle cell disease interventions: a study protocol of the Sickle Cell
Disease Implementation Consortium (SCDIC).
AB - BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder that results
in a lifetime of anemia, severe pain, and end-organ damage that can lead to
premature mortality. While the SCD field has made major medical advances, much
needs to be done to improve the quality of care for people with SCD. This study
capitalizes on the Sickle Cell Disease Implementation Consortium (SCDIC), a
consortium of eight academic sites aiming to test implementation strategies that
could lead to more accelerated application of the NHLBI guidelines for treating
SCD. This report documents the process to support the consortium by specifying
the interventions being developed. METHODS: This study consists of three steps.
The Principal Investigator of each site and two site representatives who are
knowledgeable of the intervention (e.g., study coordinator or the person
delivering the intervention) will answer an online survey aiming to capture
components of the interventions. This survey will be completed by the site
representatives three times during the study: during the development of the
interventions, after one year of the interventions being implemented, and at the
end of this study (after 2 years). A site visit and semi-structured interview
(Step 2) in the first year of the process will capture the context of the sites.
Step 3 comprises of the development of a framework with the details of the multi
component SCDIC interventions at the sites. DISCUSSION: The outcome of this
study, a framework of the SCDIC, will enable accurate replication and extension
of published research, facilitating the translation of SCD studies to diverse
populations and settings and allowing for theory testing of the effects of the
intervention components across studies in different contexts and for different
populations. TRIAL REGISTRATION: ClinicalTrial.Gov (# NCT03380351 ). Registered
December 21, 2017.
PMID- 29945632
TI - Nordic diet, Mediterranean diet, and the risk of chronic diseases: the EPIC
Potsdam study.
AB - BACKGROUND: The Mediterranean Diet (MedDiet) has been acknowledged as a healthy
diet. However, its relation with risk of major chronic diseases in non
Mediterranean countries is inconclusive. The Nordic diet is proposed as an
alternative across Northern Europe, although its associations with the risk of
chronic diseases remain controversial. We aimed to investigate the association
between the Nordic diet and the MedDiet with the risk of chronic disease (type 2
diabetes (T2D), myocardial infarction (MI), stroke, and cancer) in the EPIC
Potsdam cohort. METHODS: The EPIC-Potsdam cohort recruited 27,548 participants
between 1994 and 1998. After exclusion of prevalent cases, we evaluated baseline
adherence to a score reflecting the Nordic diet and two MedDiet scores (tMDS,
reflecting the traditional MedDiet score, and the MedPyr score, reflecting the
MedDiet Pyramid). Cox regression models were applied to examine the association
between the diet scores and the incidence of major chronic diseases. RESULTS:
During a follow-up of 10.6 years, 1376 cases of T2D, 312 of MI, 321 of stroke,
and 1618 of cancer were identified. The Nordic diet showed a statistically non
significant inverse association with incidence of MI in the overall population
and of stroke in men. Adherence to the MedDiet was associated with lower
incidence of T2D (HR per 1 SD 0.93, 95% CI 0.88-0.98 for the tMDS score and 0.92,
0.87-0.97 for the MedPyr score). In women, the MedPyr score was also inversely
associated with MI. No association was observed for any of the scores with
cancer. CONCLUSIONS: In the EPIC-Potsdam cohort, the Nordic diet showed a
possible beneficial effect on MI in the overall population and for stroke in men,
while both scores reflecting the MedDiet conferred lower risk of T2D in the
overall population and of MI in women.
PMID- 29945633
TI - Prevention of postpartum haemorrhage: a distributional approach for analysis.
AB - BACKGROUND: There is empirical evidence that measured postpartum blood loss has a
lognormal distribution. This feature can be used to analyze events of the type
'blood loss greater than a certain cutoff point' using a lognormal approach,
which takes into account all the quantitative observations, as opposed to
dichotomizing the variable blood loss volume into two categories. This lognormal
approach uses all the information contained in the data and is expected to
provide more efficient estimates of proportions and relative risk when comparing
treatments to prevent postpartum haemorrhage. As a consequence, sample size can
be reduced in clinical trials, while keeping the statistical precision
requirements. METHODS: The authors illustrate how a lognormal approach can be
used in this situation, using data from a clinical trial and the event 'blood
loss greater than 1000 mL'. RESULTS: Estimates of the proportions of this event
for each treatment, and relative risks obtained with this method are presented
and compared with the standard estimates obtained by dichotomizing measured blood
loss volume. An example of how the blood loss distributions of two treatments can
be compared is also presented. Different scenarios of the sample size needed to
compare two treatments or interventions are presented to illustrate how with the
lognormal approach the size of a clinical trial can be reduced. CONCLUSIONS: A
distributional approach for postpartum blood loss using the lognormal
distribution fitted to the data results in more precise estimates of risks of
events and relative risks, compared to the use of binomial proportions of events.
It also results in reduced required sample size for clinical trials. TRIAL
REGISTRATION: This paper reports a secondary analysis for a trial that was
registered at clinicaltrials.gov ( NCT00781066 ).
PMID- 29945634
TI - Decision-making criteria for medicine reimbursement in Slovenia: an expert panel
discussion.
AB - BACKGROUND: Rational and transparent Health Technology Assessment and
reimbursement decision-making are crucial for healthcare system sustainability. A
part of the reimbursement process are decision-making criteria which should be
clearly defined. METHODS: The study aimed to obtain an insight into understanding
and relevance of potential criteria for the medicine reimbursement decision
making process in Slovenia. A semi-structured guided focus panel was performed in
June 2017 with five Slovenian experts covering principal healthcare system
sectors. First, criteria understanding and relevance for medicine reimbursement
decision-making were discussed. Second, healthcare priorities and societal values
affecting decision-making were debated. The analysis was carried out with NVivo
11 by two independent researchers who coded the verbatim transcript in three
coding steps based on the experts' interpretations and original ideas. RESULTS:
Seven decision-making criteria were derived. Among those, the impact a disease
has on the lives of patient family and caregivers and the indirect medicine
benefit for them were new aspects comparing to the existing criteria set in
Slovenia. The experts expressed that the same decision-making criteria are
relevant for evaluating any health technology, allowing for different criteria
weights. They also suggested a system that would allow re-evaluation of
reimbursement decisions once real-world clinical data are available. CONCLUSIONS:
As proposed by the international frameworks and tools, the Slovenian healthcare
experts consider including multiple aspects more ethical and comprehensive than
considering a single criterion, e.g. cost-effectiveness, existing in some
healthcare systems. They recognize that in the existing decision-making process,
health perspectives of the public represent a largely missed aspect.
PMID- 29945635
TI - Neutrophil-lymphocyte ratio predicts recurrence in patients with resected stage 1
non-small cell lung cancer.
AB - BACKGROUND: The aim was to determine the prognostic value of the neutrophil
lymphocyte ratio (NLR) in patients with completely resected stage 1 non-small
cell lung cancer (NSCLC). METHODS: The study enrolled 382 NSCLC patients, and an
optimal NLR cutoff value was determined by ROC analysis. Patients were divided by
preoperative NLR into low (< 1.5, n = 99), intermediate (1.5 <= NLR < 3.5, n =
245), and high (NLR >= 3.5, n = 38) value groups. Serum diacron-reactive oxygen
metabolites (d-ROMs) were assayed in 33 consecutive patients and used as an
indicator of oxidative stress. RESULTS: The mean NLR in patients with high d-ROMs
(> 300 U.CARR, n = 16) was 1.72 +/- 0.67, which was significantly higher than
that in patients with low d-ROMs (1.41 +/- 0.39, n = 17; P = 0.018). The 3-, 5-
and 10-year survival rates in the three NLR groups were 92, 77, and 59% (low);
82, 70, and 50% (intermediate); and 76, 58, and 32% (high) (P = 0.034). The 1-, 3
and 5-year recurrence-free survival rates in the three groups were 98, 90, and
86% (low), 91, 77, and 74% (intermediate); and 92, 77, and 68% (high) (P =
0.033). Multivariate analysis found that although NLR was not predictive of
overall survival, high NLR was an independent risk factor of recurrence (hazard
ratio: 2.03, 95% confidence interval: 1.17-3.79, P = 0.011) as were as age,
pathological stage, tumor differentiation, and lymph-vascular invasion.
CONCLUSIONS: A low preoperative NLR predicted good prognosis, and was associated
with low systemic inflammation status in patients with stage 1 NSCLC. It may be
helpful when considering intervals of routine follow-up or choice of adjuvant
therapy.
PMID- 29945636
TI - Monte Carlo simulations in radiotherapy dosimetry.
AB - BACKGROUND: The use of the Monte Carlo (MC) method in radiotherapy dosimetry has
increased almost exponentially in the last decades. Its widespread use in the
field has converted this computer simulation technique in a common tool for
reference and treatment planning dosimetry calculations. METHODS: This work
reviews the different MC calculations made on dosimetric quantities, like
stopping-power ratios and perturbation correction factors required for reference
ionization chamber dosimetry, as well as the fully realistic MC simulations
currently available on clinical accelerators, detectors and patient treatment
planning. CONCLUSIONS: Issues are raised that include the necessity for
consistency in the data throughout the entire dosimetry chain in reference
dosimetry, and how Bragg-Gray theory breaks down for small photon fields. Both
aspects are less critical for MC treatment planning applications, but there are
important constraints like tissue characterization and its patient-to-patient
variability, which together with the conversion between dose-to-water and dose-to
tissue, are analysed in detail. Although these constraints are common to all
methods and algorithms used in different types of treatment planning systems,
they make uncertainties involved in MC treatment planning to still remain
"uncertain".
PMID- 29945637
TI - Frequency of rare and multi viral high-risk HPV types infection in cervical high
grade squamous intraepithelial lesions in a non-native dominant middle eastern
country: a polymerase chain reaction-based pilot study.
AB - BACKGROUND: The incidence of abnormal cervical smears in the United Arab Emirates
(UAE) is 3.6%. Data regarding specific high-risk HPV (hrHPV) genotypes are
insufficient. Identification of hrHPV subtypes is essential to allow formulating
effective vaccination strategies. METHODS: A total of 75 archival cervical cone
biopsies with HSIL or higher lesions (2012-2016) were retrieved from a tertiary
hospital, including HSIL (n = 70), adenocarcinoma in-situ (n = 1) and squamous
cell carcinoma (n = 4). Five tissue sections (10-MU-thick each) were cut and DNA
extracted using the QIAamp DNA FFPE Tissue Kit. GenomeMeTM's GeneNavTM HPV One
qPCR Kit was used for specific detection of HPV 16 and 18; and non-16/18 samples
were typed by GenomeMeTM's GeneNavTM HPV Genotyping qPCR Kit. RESULTS: Median age
was 34 years (range 19-58) with 70% UAE Nationals. hrHPV detected were 16, 18,
31, 33, 35, 39, 45, 51, 52, 58, 59, 66 & 68. hrHPV testing was negative in 12% of
cases. Most common types were HPV 16 (49%), HPV 31 (20%) and HPV 18 (6.6%). hrHPV
16 and/or 18 represented 56% and rare subtypes 32%. Co-infection was present in
16%. Eight cases had two-viral subtype infections and 4 cases had 3 subtype
infections. Multi-viral HPV infection was limited to hrHPV 16, 18, 31 & 33
subtypes. CONCLUSIONS: Infection by non HPV 16/18 is fairly common. A higher than
expected incidence of rare subtype (20% hrHPV31) and multi-viral hrHPV (16%) were
detected. This finding stresses the importance of this pilot study as currently
only quadravalent vaccine is offered to control the HPV infection in the UAE
population.
PMID- 29945638
TI - Mechanisms and modulators of cognitive training gain transfer in cognitively
healthy aging: study protocol of the AgeGain study.
AB - BACKGROUND: Cognitively healthy older people can increase their performance in
cognitive tasks through training. However, training effects are mostly limited to
the trained task; thus, training effects only poorly transfer to untrained tasks
or other contexts, which contributes to reduced adaptation abilities in aging.
Stabilizing transfer capabilities in aging would increase the chance of
persistent high performance in activities of daily living including longer
independency, and prolonged active participation in social life. The trial
AgeGain aims at elaborating the physiological brain mechanisms of transfer in
aging and supposed major modulators of transfer capability, especially physical
activity, cerebral vascular lesions, and amyloid burden. METHODS: This 4-year
interventional, multicenter, phase 2a cognitive and physical training study will
enroll 237 cognitively healthy older subjects in four recruiting centers. The
primary endpoint of this trial is the prediction of transfer of cognitive
training gains. Secondary endpoints are the structural connectivity of the corpus
callosum, Default Mode Network activity, brain-derived neurotrophic factors,
motor fitness, and maximal oxygen uptake. DISCUSSION: Cognitive transfer allows
making use of cognitive training gains in everyday life. Thus, maintenance of
transfer capability with aging increases the chance of persistent self-guidance
and prolonged active participation in social life, which may support a good
quality of life. The AgeGain study aims at identifying older people who will most
benefit from cognitive training. It will increase the understanding of the
neurobiological mechanisms of transfer in aging and will help in determining the
impact of physical activity and sport as well as pathologic factors (such as
cerebrovascular disease and amyloid load) on transfer capability. TRIAL
REGISTRATION: German Clinical Trials Register (DRKS), ID: DRKS00013077 .
Registered on 19 November 2017.
PMID- 29945639
TI - Longitudinal hearing loss in Wolfram syndrome.
AB - BACKGROUND: Wolfram syndrome (WFS) is a rare autosomal recessive disease with
clinical manifestations of diabetes mellitus (DM), diabetes insipidus (DI), optic
nerve atrophy (OA) and sensorineural hearing loss (SNHL). Although SNHL is a key
symptom of WFS, there is limited information on its natural history using
standardized measures. Such information is important for clinical care and
determining its use as an outcome measure in clinical trials. METHODS:
Standardized audiologic measures, including pure-tone testing, tympanometry,
speech perception, and the unaided Speech Intelligibility Index (SII) were
assessed in patients with confirmed WFS annually. Mixed model analyses were used
to examine main effects of age, time or interactions for pure tone average (PTA),
high frequency average (HFA) and SII. RESULTS: Forty WFS patients were evaluated
between 1 and 6 times. Mean age at initial enrollment was 13.5 years (SD = 5.6).
Patients were classified as having normal hearing (n = 10), mild-to-severe (n =
24) or profound SNHL (n = 6). Mean age of diagnosis for SNHL was 8.3 years (SD =
5.1) with 75% prevalence. HFA worsened over time for both ears, and SII worsened
over time in the worse ear, with greater decline in both measures in younger
patients. Average estimated change over 1 year for all measures was in the
subclinical range and power analyses suggest that 100 patients would be needed
per group (treatment vs. placebo) to detect a 60% reduction in annual change of
HFA over 3 years. If trials focused on just those patients with SNHL, power
estimates suggest 55 patients per group would be sufficient. CONCLUSIONS: Most
patients had a slow progressive SNHL emerging in late childhood. Change over time
with standard audiologic tests (HFA, SII) was small and would not be detectable
for at least 2 years in an individual. Relatively large sample sizes would be
necessary to detect significant impact on hearing progression in a clinical
trial. Hearing function should be monitored clinically in WFS to provide
appropriate intervention. Because SNHL can occur very early in WFS, audiologists
and otolaryngologists should be aware of and refer for later emerging symptoms.
PMID- 29945640
TI - Current research on carbetocin and implications for prevention of postpartum
haemorrhage.
AB - BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal
mortality in low-income countries and is a significant contributor to severe
maternal morbidity and long-term disability. Carbetocin may be an underused
uterotonic for prevention of PPH. A number of studies are being conducted that
may challenge the place of oxytocin as the first choice of uterotonics for
prevention of PPH. This paper describes the current research into carbetocin and
ranking of effectiveness of uterotonics that may provide important new
information to assist healthcare decision makers to ensure that women receive an
effective uterotonic for prevention of PPH. METHODS: We searched the WHO
International Clinical Trials Registry Platform for current studies on
effectiveness of carbetocin for prevention of PPH following vaginal delivery with
sample sizes large enough to provide quality evidence to support potential
changes to international guidelines. We also searched the Cochrane Library for
current systematic reviews including carbetocin used in prevention of PPH.
RESULTS: Susceptibility to degradation from exposure to heat is one of the key
causes of reduced effectiveness of oxytocin in preventing PPH from uterine atony.
Although heat stable and effective in preventing PPH, misoprostol is also subject
to degradation due to exposure to moisture and produces some side-effects. Other
uterotonics (including ergometrine and combinations of oxytocin, ergometrine and
misoprostol) are also available and used with varying safety and effectiveness
profiles and quality issues. Efforts to reduce maternal mortality from PPH
include research studies seeking to identify safe, stable, effective uterotonics.
Heat stable carbetocin is the subject of two major clinical studies into its
effectiveness in preventing PPH following vaginal deliveries, information that
could expand its application for prevention of PPH. CONCLUSION: Heat stable
carbetocin is being investigated as a potential alternative to oxytocin. This
paper describes two current clinical trials on carbetocin and a network meta
analysis ranking of all uterotonic agents, including carbetocin, which combined
may provide evidence supporting expansion of the use of the heat stable
formulation of carbetocin in PPH prevention.
PMID- 29945641
TI - Innovations in vital signs measurement for the detection of hypertension and
shock in pregnancy.
AB - Approximately 820 women die in pregnancy and childbirth every day worldwide, with
99% of these occurring in low-resource settings. The most common causes of
maternal mortality are haemorrhage, sepsis and hypertensive disorders. There are
established, effective solutions to these complications, however challenges
remain in identifying who is at greatest risk and ensuring that interventions are
delivered early when they have the greatest potential to benefit. Measuring vital
signs is the first step in identifying women at risk. Overstretched or poorly
trained staff and inadequate access to accurate, reliable equipment to measure
vital signs can potentially result in delayed treatment initiation. Early warning
systems may help alert users to identify patients at risk, especially where novel
technologies can improve usability by automating calculations and alerting users
to abnormalities. This may be of greatest benefit in under-resourced settings
where task-sharing is common and early identification of complications can allow
for prioritisation of life-saving interventions. This paper highlights the
challenges of accurate vital sign measurement in pregnancy and identifies
innovations which may improve detection of pregnancy complications.
PMID- 29945642
TI - Thymoma and thymic carcinoma associated with multilocular thymic cyst: a
clinicopathologic analysis of 18 cases.
AB - BACKGROUND: Multilocular thymic cysts (MTCs) associated with thymomas or thymic
carcinomas (TCs) are rare and may be misdiagnosed as other benign cystic lesions.
METHODS: We retrospectively analysed 18 cases of thymomas or TCs associated with
MTCs, which were retrieved from 309 consecutive patients with thymomas or TCs in
the Chinese population, emphasizing clinicopathologic characteristics,
immunophenotypes and the prognostic impact. RESULTS: A total of 14 tumours were
described as cystic or solid-cystic masses, and the other 4 tumours were
described as solid masses. Histologically, 2 atypical type A, 2 type AB, 1 type
B1, 8 type B2, 1 type B3, 1 microscopic thymoma (type A), 2 squamous cell
carcinomas (SCCs) and 1 lymphoepithelioma-like carcinoma (LELC) were classified.
Prominent multilocular cystic areas with chronic inflammation were observed. The
follow-up ranged from 2 to 79 months. Sixteen patients survived without any
evidence of recurrence after complete resection. CONCLUSIONS: Our study suggests
that thymomas or TCs associated with MTCs are rare in the Chinese population and
have a better clinical behaviour than thymomas or TCs without MTCs. Our data also
expand the histologic spectrum of thymomas or TCs accompanied by MTC. To our
knowledge, this is the first report of atypical type A thymoma and LELC
associated with MTCs.
PMID- 29945643
TI - Iron deficiency and iron treatment in the fetal developing brain - a pilot study
introducing an experimental rat model.
AB - BACKGROUND: Iron deficiency is especially common in women during the reproductive
age and it is estimated that 52% of pregnant women have iron deficiency anemia.
Maternal iron deficiency with or without anemia in pregnancy may have
consequences for the fetus, where it may have an impact on the cerebral
development of the brain. Both animals and adult human studies support that iron
deficiency affects psychomotor development, behavioral traits, and cognitive
functions in the offspring. However, it has not yet been established whether the
availability of sufficient iron is particularly important in certain phases
during brain development, and whether possible damages are reversible if iron
supplementation is provided during pregnancy. Here we report results from a pilot
study in an experimental rat model suitable for introducing iron deficiency in
the fetal rat brain. METHODS: The model was utilized for examination of the
potential to reverse changes in fetal brain iron by maternal parenteral iron
administration. Fertilized females subjected to iron deficiency without anemia
were subcutaneously injected with iron isomaltoside at the day of mating (E0), 14
days into pregnancy (E14), or at the day of birth (Postnatal (P) 0). Blood, brain
and liver in the offspring were examined on P0 or in adulthood on postnatal day
P70. RESULTS: Maternal iron restriction during pregnancy led to significantly
lower levels of iron in the brains of newborn rats compared to levels in pups of
iron sufficient mothers. Females fed ID diet (5.2 mg/kg Fe) had offspring with
significantly lower cerebral iron compared to a control group fed a standard diet
(158 mg/kg Fe). Injection of IIM to pregnant ID females on E0 or E14 yielded
normalization of Fe in the developing brain known to express elevated levels of
capillary transferrin receptors, indicating that the administered iron passed the
placenta and fetal blood brain barrier. CONCLUSIONS: In future studies, this
translational model may be applied to examine morphological and biochemical
consequences of iron deficiency and iron deficiency treatment in the developing
fetal brain.
PMID- 29945644
TI - "Reality rarely looks like the guidelines": a qualitative study of the challenges
hospital-based physicians encounter in war wound management.
AB - BACKGROUND: Globally, armed conflict is a major contributor to mortality and
morbidity. The treatment of war-associated injuries is largely experience-based.
Evidence is weak due to difficulty in conducting medical research in war
settings. A qualitative method could provide insight into the specific challenges
associated with providing health care to injured civilians. The aim of this study
was to explore the challenges hospital-based physicians encounter in war wound
management, focusing on surgical intervention and antibiotic use. METHODS: Semi
structured, face-to-face interviews were conducted with physicians at a Jordanian
hospital supported by Medecins Sans Frontieres. The interviews were recorded,
transcribed verbatim and analysed using content analysis with an inductive and
deductive approach. RESULTS: We found that challenges in war wound management
primarily relate to protocol adherence. Protocols for the management of acute war
wounds were adhered to on areas that could be considered commonly agreed
principles of war wound surgery, such as the use of wound debridement and the
evaluation of the systemic condition of the patient before initiating antibiotic
treatment. We identified limitations imposed on the physicians that complicate or
even hinder protocol adherence. Additionally, we identified factors associated
with conscious deviations from the protocols. CONCLUSIONS: We conclude that
adherence to established protocols around the management of acute war wounds is
difficult. We present aspects that may be considered when establishing clinical
projects in similar contexts. The knowledge gained by this study could provide
insights for the development of protocols or guidelines for wound management and
antibiotic use in an unstable setting, such as a hospital in close proximity to
armed conflict. We suggest the use of a grounded theory approach to further study
the discrepancy between guideline recommendations and actual practice.
PMID- 29945645
TI - Early pregnancy loss in Belagavi, Karnataka, India 2014-2017: a prospective
population-based observational study in a low-resource setting.
AB - BACKGROUND: The prevalence of early pregnancy loss through miscarriage and
medically terminated pregnancy (MTP) is largely unknown due to lack of early
registration of pregnancies in most regions, and especially in low- and middle
income countries. Understanding the rates of early pregnancy loss as well as the
characteristics of pregnant women who experience miscarriage or MTP can assist in
better planning of reproductive health needs of women. METHODS: A prospective,
population-based study was conducted in Belagavi District, south India. Using an
active surveillance system of women of childbearing age, all women were enrolled
as soon as possible during pregnancy. We evaluated rates and risk factors of
miscarriage and MTP between 6 and 20 weeks gestation as well as rates of
stillbirth and neonatal death. A hypothetical cohort of 1000 women pregnant at 6
weeks was created to demonstrate the impact of miscarriage and MTP on pregnancy
outcome. RESULTS: A total of 30,166 women enrolled from 2014 to 2017 were
included in this analysis. The rate of miscarriage per 1000 ongoing pregnancies
between 6 and 8 weeks was 115.3, between 8 and 12 weeks the miscarriage rate was
101.9 per 1000 ongoing pregnancies and between 12 and 20 weeks the miscarriage
rate was 60.3 per 1000 ongoing pregnancies. For those periods, the MTP rate was
40.2, 45.4, and 48.3 per 1000 ongoing pregnancies respectively. The stillbirth
rate was 26/1000 and the neonatal mortality rate was 24/1000. The majority of
miscarriages (96.6%) were unattended and occurred at home. The majority of MTPs
occurred in a hospital and with a physician in attendance (69.6%), while 20.7% of
MTPs occurred outside a health facility. Women who experienced a miscarriage were
older and had a higher level of education but were less likely to be anemic than
those with an ongoing pregnancy at 20 weeks. Women with MTP were older, had a
higher level of education, higher parity, and higher BMI, compared to those with
an ongoing pregnancy, but these results were not consistent across gestational
age periods. CONCLUSIONS: Of women with an ongoing pregnancy at 6 weeks, about
60% will have a living infant at 28 days of age. Two thirds of the losses will be
spontaneous miscarriages and one third will be secondary to a MTP. High maternal
age and education were the risk factors associated with miscarriage and MTP.
TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov.
ClinicalTrial.gov Trial Registration: NCT01073475 .
PMID- 29945646
TI - Anomaly of Haughton type D left cervical aortic arch in combination with type B
dissection: case report and literature review.
AB - BACKGROUND: The anomaly of cervical aortic arch is a rare phenomenon first
described by Reid in 1914 and categorized by Haughton in 1975. The left cervical
aortic arch Type D consisting of an ipsilateral descending aorta and coarctation
or aneurysmatic formation of the arch demonstrates a complicated form requiring
surgical management. Because of its rarity and unspecific symptoms only few cases
are documented with the focus on surgical management. CASE PRESENTATION: A 43
year old, asymptomatic woman presented with a mediastinal mass overlapping the
aortic arch region in a routine x-ray. For verification, a computed tomography
was performed and revealed incidentally a type B dissection originating from an
aneurysm of a left cervical arch with a maximum diameter of 6 cm. Because of the
huge diameter and the potential risk of rupture, an urgent surgical repair was
planned. Surgical access was performed through median sternotomy and an
additional left lateral thoracic incision through the fourth intercostal space.
Simultaneously to the preparation, partial cardiopulmonary bypass was installed
in the left groin. After preparation of the recurrent and phrenic nerve and the
supraaortic branches, the descending aorta was clamped. Before the distal
anastomosis to a straight graft, we performed a fenestration of the dissection
membrane about a length of 5 cm to preserve the perfusion of both lumina. Then,
the straight graft was sutured to the proximal part of descending aorta. The left
axillary artery originated directly from the aneurysm and was dissected and
reimplanted with a separate 8 mm sidegraft to the straight graft between the
distal arch and proximal descending aorta. The patient was extubated on first
postoperative day and recovered well. CONCLUSION: The left cervical aortic arch
type D is a rare disease, which is prone to aneurysm formation due to abnormal
flow patterns and tortuosity of the aorta. The difficulty lays in the
identification of the pathology, especially in the physical examination, since a
pulsating mass or cervical murmur seem to be the most specific symptoms in the
majority of young, female patients. If diagnosed, surgical therapy with resection
of the aneurysm and reimplantation of the axillary artery under cardiopulmonary
bypass demonstrates the treatment of choice.
PMID- 29945647
TI - Trends and determinants of stillbirth in developing countries: results from the
Global Network's Population-Based Birth Registry.
AB - BACKGROUND: Stillbirth rates remain high, especially in low and middle-income
countries, where rates are 25 per 1000, ten-fold higher than in high-income
countries. The United Nations' Every Newborn Action Plan has set a goal of 12
stillbirths per 1000 births by 2030 for all countries. METHODS: From a population
based pregnancy outcome registry, including data from 2010 to 2016 from two sites
each in Africa (Zambia and Kenya) and India (Nagpur and Belagavi), as well as
sites in Pakistan and Guatemala, we evaluated the stillbirth rates and rates of
annual decline as well as risk factors for 427,111 births of which 12,181 were
stillbirths. RESULTS: The mean stillbirth rates for the sites were 21.3 per 1000
births for Africa, 25.3 per 1000 births for India, 56.9 per 1000 births for
Pakistan and 19.9 per 1000 births for Guatemala. From 2010 to 2016, across all
sites, the mean stillbirth rate declined from 31.7 per 1000 births to 26.4 per
1000 births for an average annual decline of 3.0%. Risk factors for stillbirth
were similar across the sites and included maternal age < 20 years and age > 35
years. Compared to parity 1-2, zero parity and parity > 3 were both associated
with increased stillbirth risk and compared to women with any prenatal care,
women with no prenatal care had significantly increased risk of stillbirth in all
sites. CONCLUSIONS: At the current rates of decline, stillbirth rates in these
sites will not reach the Every Newborn Action Plan goal of 12 per 1000 births by
2030. More attention to the risk factors and treating the causes of stillbirths
will be required to reach the Every Newborn Action Plan goal of stillbirth
reduction. TRIAL REGISTRATION: NCT01073475 .
PMID- 29945648
TI - Strategies for optimizing maternal nutrition to promote infant development.
AB - BACKGROUND: The growing appreciation of the multi-faceted importance of optimal
maternal nutrition to the health and development of the infant and young child is
tempered by incompletely resolved strategies for combatting challenges.
OBJECTIVE: To review the importance of maternal nutrition and strategies being
employed to optimize outcomes. METHODS: Selected data from recent literature with
special focus on rationale for and currently published results of maternal
nutrition supplements, including lipid based nutrition supplements. RESULTS: 1)
An impelling rationale for improving the maternal and in utero environment of low
resource populations has emerged to achieve improved fetal and post-natal growth
and development. 2) Based partly on population increases in adult height over one
two generations, much can be achieved by reducing poverty. 3) Maternal, newborn
and infant characteristics associated with low resource environments include
evidence of undernutrition, manifested by underweight and impaired linear growth.
4) Apart from broad public health and educational initiatives, to date, most
specific efforts to improve fetal growth and development have included maternal
nutrition interventions during gestation. 5) The relatively limited but real
benefits of both iron/folic acid (IFA) and multiple micronutrient (MMN) maternal
supplements during gestation have now been reasonably defined. 6) Recent
investigations of a maternal lipid-based primarily micronutrient supplement (LNS)
have not demonstrated a consistent benefit beyond MMN alone. 7) However, effects
of both MMN and LNS appear to be enhanced by commencing early in gestation.
CONCLUSIONS: Poor maternal nutritional status is one of a very few specific
factors in the human that not only contributes to impaired fetal and early post
natal growth but for which maternal interventions have demonstrated improved in
utero development, documented primarily by both improvements in low birth weights
and by partial corrections of impaired birth length. A clearer definition of the
benefits achievable by interventions specifically focused on correcting maternal
nutrition deficits should not be limited to improvements in the quality of
maternal nutrition supplements, but on the cumulative quantity and timing of
interventions (also recognizing the heterogeneity between populations). Finally,
in an ideal world these steps are only a prelude to improvements in the total
environment in which optimal nutrition and other health determinants can be
achieved.
PMID- 29945649
TI - Commentary: Iron deficiency of pregnancy - a new approach involving intravenous
iron.
AB - Iron deficiency anemia of pregnancy is common, especially in South Asia, and is
associated with adverse maternal and fetal outcomes including increased
incidences of maternal mortality, preterm labor and low birth weight. Screening
for anemia alone is not sufficient to diagnose iron deficiency. Iron deficiency
in neonates is associated with a statistically significant increment in cognitive
and behavioral abnormalities which persist after iron repletion. Oral iron is the
frontline standard but is associated with an unacceptably high incidence of
gastrointestinal adverse events leading to poor adherence. Prospective evidence
reports an incidence of neonatal iron deficiency up to 45% even with oral iron
supplementation. New evidence reports oral iron ingestion increases serum
hepcidin leading to decreased absorption suggesting further decreasing efficacy.
Published evidence reports that intravenous iron is safe and effective in the
second and third trimesters of pregnancy. Intravenous iron is the preferred route
when there is oral iron intolerance or in those situations where oral iron is
ineffective or harmful. Intravenous iron is also preferred if the anemia is
severe (< 8 g/dL) in the second trimester or at any time in the third trimester
when there is little expectation that adequate quantities of iron will be
delivered to the fetus as iron requirements increase in each trimester.
Guidelines for maternal and neonatal screening and treatment lack consistency and
differ between the United States and Europe. New formulations of intravenous iron
with complex carbohydrate cores that bind elemental iron more tightly mitigating
the release of large quantities of labile free iron allow the administration of
complete replacement doses in 15-60 min. The preponderance of published evidence
suggests that intravenous iron is underutilized in pregnancy and guidelines
suggesting there is insufficient evidence to recommend the routine screening and
treatment of iron deficiency in gravidas should be revisited. The major
recommendation from this commentary is that in low-income countries, a trial or
demonstration project to test the efficacy, safety, cost and feasibility of the
administration of intravenous iron to anemic and/or iron-deficient women be
undertaken.
PMID- 29945650
TI - Psychological distress following a motor vehicle crash: preliminary results of a
randomised controlled trial investigating brief psychological interventions.
AB - BACKGROUND: The preliminary results of a randomised controlled trial are
presented. The aim of the trial is to determine the efficacy, feasibility and
acceptability of email-delivered psychological interventions with telephone
support, for adults injured in a motor vehicle crash engaged in seeking
compensation. The primary intention for this preliminary analysis was to
investigate those who were psychologically distressed and to stop the trial
midway to evaluate whether the safety endpoints were necessary. METHODS: The
analysis included 90 adult participants randomised to one of three groups, who
were assessed at baseline and post-intervention at 3 months. Cognitive behaviour
therapy (CBT) or healthy lifestyle interventions were delivered over 10 weeks,
involving fortnightly emailed modules plus clinically focussed telephone support,
with the aim of reducing psychological distress. An active waiting list of
control subjects received non-clinically focussed telephone contact over the same
period along with claim-related reading material. Depression Anxiety Stress
Scales (DASS) and Impact of Events Scale (Revised) (IES-R) were used to assess
psychological distress. Psychiatric interviews were used to diagnose major
depressive disorder and post-traumatic stress disorder. Aspects of acceptability
and feasibility were also assessed. RESULTS: For those diagnosed with depression
at baseline in the CBT group, psychological distress reduced by around 16%. For
those with depression in the healthy lifestyle group, distress increased
marginally. For those in the control group with depression, distress also
decreased (by 18% according to DASS-21 and 1.2% according to IES-R). For those
without depression, significant reductions in distress occurred, regardless of
group (P < .05). The results suggest that for those with depression, a healthy
lifestyle intervention is contraindicated, necessitating the cessation of
recruitment to this intervention. The interventions were reported as acceptable
by the majority and the data indicated that the study is feasible. CONCLUSIONS:
CBT with telephone support reduced psychological distress in physically injured
people with depression who are engaged in seeking compensation. However, time
plus fortnightly telephone contact with claim-related reading material may be
sufficient to reduce distress in those who are depressed. For those who were not
depressed, time plus telephone support is most likely sufficient enough to assist
them to recover. The trial will continue with further recruitment to only the CBT
and control groups, over longer follow-up periods. TRIAL REGISTRATION: Australian
and New Zealand Clinical Trials Registry: Preventing psychological distress
following a motor vehicle accident; ACTRN12615000326594 . Registered on 9 April
2015.
PMID- 29945652
TI - Neoadjuvant chemotherapy regimens in treatment of breast cancer: a systematic
review and network meta-analysis protocol.
AB - BACKGROUND: Neoadjuvant chemotherapy (NACT), a standard of care for locally
advanced breast cancer patients, is widely used for early breast cancer patients
also. The varying role of regimens used as NACT needs to be investigated. Despite
availability of some randomized controlled trials (RCTs), it is unclear which
treatment regimen suits best. Further, there is no study comparing all the three
regimens. Accordingly, present study will compare the efficacy of anthracyclines,
taxanes, and targeted therapy administered in neoadjuvant setting on the basis of
oncological outcomes and functional outcomes. METHOD/DESIGN: Online databases
PubMed and Cochrane Register of Controlled Trials will be searched to acquire
eligible studies. Further, content of relevant journals, references of relevant
articles, and proceedings of major related conference will also be searched. The
RCTs comparing any of abovementioned regimen as NACT on breast cancer patients
will be eligible. Two reviewers independently and in duplicate will screen the
records on the basis of title and abstract and complete full-text review to
determine eligibility. Similarly, data extraction and risk of bias assessment
will be done by two independent reviewers. The pair-wise meta-analysis as well as
network meta-analysis will be conducted to assess the relative efficacy of
anthracyclines, taxanes, and targeted therapy regimens. DISCUSSION: The present
systematic review will improve the understanding of the relative efficacies of
the three treatment regimens and possibly guide the clinical practices by
providing the current best evidence on the efficacy of various regimens of NACT
in the management of breast cancer patients. SYSTEMATIC REVIEW REGISTRATION:
PROSPERO ( CRD42016027236 ).
PMID- 29945651
TI - The project to understand and research preterm pregnancy outcomes and stillbirths
in South Asia (PURPOSe): a protocol of a prospective, cohort study of causes of
mortality among preterm births and stillbirths.
AB - BACKGROUND: In South Asia, where most stillbirths and neonatal deaths occur, much
remains unknown about the causes of these deaths. About one-third of neonatal
deaths are attributed to prematurity, yet the specific conditions which cause
these deaths are often unclear as is the etiology of stillbirths. In low-resource
settings, most women are not routinely tested for infections and autopsy is rare.
METHODS: This prospective, cohort study will be conducted in hospitals in
Davengere, India and Karachi, Pakistan. All women who deliver either a stillbirth
or a preterm birth at one of the hospitals will be eligible for enrollment. With
consent, the participant and, when applicable, her offspring, will be followed to
28-days post-delivery. A series of research tests will be conducted to determine
infection and presence of other conditions which may contribute to the death. In
addition, all routine clinical investigations will be documented. For both
stillbirths and preterm neonates who die <= 28 days, with consent, a standard
autopsy as well as minimally invasive tissue sampling will be conducted. Finally,
an expert panel will review all available data for stillbirths and neonatal
deaths to determine the primary and contributing causes of death using pre
specified guidance. CONCLUSION: This will be among the first studies to
prospectively obtain detailed information on causes of stillbirth and preterm
neonatal death in low-resource settings in Asia. Determining the primary causes
of death will be important to inform strategies most likely to reduce the high
mortality rates in South Asia. TRIAL REGISTRATION: Clinicaltrials.gov (
NCT03438110 ) Clinical Trial Registry of India ( CTRI/2018/03/012281 ).
PMID- 29945653
TI - Developing Zika vaccines: the lessons for disease X.
AB - There is an urgent need to develop vaccines against emerging diseases, including
those caused by pathogens that are currently unknown to cause human disease,
termed 'disease X'. Here, Zika virus infection is considered as an example of
disease X. The speed of Zika vaccine development provides optimism for our
ability to prepare vaccines against unknown pathogens.
PMID- 29945654
TI - Overcoming challenges to dissemination and implementation of research findings in
under-resourced countries.
AB - Louis Pasteur once commented on the happiness that a scientist finds when,
besides making a discovery, study results find practical application. Where
health status is poor and resources are limited, finding such applications is a
necessity, not merely a joy.Dissemination, or the distribution of new knowledge
gained through research, is essential to the ethical conduct of research.
Further, when research is designed to improve health, dissemination is critical
to the development of evidence-based medicine and the adoption of evidence
supported interventions and improved practice patterns within specific settings.
When dissemination is lacking, research may be considered a waste of resources
and a useless pursuit unable to influence positive health outcomes.Effective
translation of the findings of health research into policy and the practice of
medicine has been slow in many countries considered low or lower middle-income
(as defined by the World Bank). This is because such countries often have health
care systems that are under-resourced (e.g., lacking personnel or facilities) and
thus insufficiently responsive to health needs of their populations. However,
implementation research has produced many tools and strategies that can prompt
more effective and timelier application of research findings to real world
situations.A conscientious researcher can find many suggestions for improving the
integration of research evidence into practice. First and foremost, the truthful
reporting of results is emphasized as essential because both studies with
desirable findings as well those with less than ideal results can provide new and
valuable knowledge. Consideration in advance of the audience likely to be
interested in study findings can result in suitable packaging and targeted
communication of results. Other strategies for avoiding the barriers that can
negatively impact implementation of research evidence include the early
involvement of stakeholders as research is being designed and discussion before
initiation of proposed research with those who will be affected by it. It is also
important to recognize the role of education and training for ensuring the skills
and knowledge needed for not only the conduct of high quality research but also
for the meaningful promotion of results and application of research findings to
achieve intended purposes.
PMID- 29945655
TI - DeepCRISPR: optimized CRISPR guide RNA design by deep learning.
AB - A major challenge for effective application of CRISPR systems is to accurately
predict the single guide RNA (sgRNA) on-target knockout efficacy and off-target
profile, which would facilitate the optimized design of sgRNAs with high
sensitivity and specificity. Here we present DeepCRISPR, a comprehensive
computational platform to unify sgRNA on-target and off-target site prediction
into one framework with deep learning, surpassing available state-of-the-art in
silico tools. In addition, DeepCRISPR fully automates the identification of
sequence and epigenetic features that may affect sgRNA knockout efficacy in a
data-driven manner. DeepCRISPR is available at http://www.deepcrispr.net/ .
PMID- 29945656
TI - Automated recruitment and randomisation for an efficient randomised controlled
trial in primary care.
AB - BACKGROUND/AIMS: Use of electronic health records and information technology to
deliver more efficient clinical trials is attracting the attention of research
funders and researchers. We report on methodological issues and data quality for
a comparison of 'automated' and manual (or 'in-practice') methods for recruitment
and randomisation in a large randomised controlled trial, with individual patient
allocation in primary care. METHODS: We conducted a three-arm randomised
controlled trial in primary care to evaluate interventions to improve the uptake
of invited NHS health checks for cardiovascular risk assessment. Eligible
participants were identified using a borough-wide health check management
information system. An in-practice recruitment and randomisation method used at
12 general practices required the research team to complete monthly visits to
each general practice. For the fully automated method, employed for six general
practices, randomisation of eligible participants was performed automatically and
remotely using a bespoke algorithm embedded in the health check management
information system. RESULTS: There were 8588 and 4093 participants recruited for
the manual and automated methods, respectively. The in-practice method was ready
for implementation 3 months sooner than the automated method and the in-practice
method allowed for full control and documentation of the randomisation procedure.
However the in-practice approach was labour intensive and the requirement for
participant records to be stored locally resulted in the loss of data for 10
practice months. No records for participants allocated using the automated method
were lost. A fixed-effects meta-analysis showed that effect estimates for the
primary outcome were consistent for the two allocation methods. CONCLUSIONS: This
trial demonstrated the feasibility of automated recruitment and randomisation
methods into a randomised controlled trial performed in primary care. Future
research should explore the application of these techniques in other clinical
contexts and health care settings. TRIAL REGISTRATION: Current Controlled Trials,
ID: ISRCTN42856343 . Registered on 21 March 2013.
PMID- 29945657
TI - A global view of severe maternal morbidity: moving beyond maternal mortality.
AB - BACKGROUND: Maternal mortality continues to be of great public health importance,
however for each woman who dies as the direct or indirect result of pregnancy,
many more women experience life-threatening complications. The global burden of
severe maternal morbidity (SMM) is not known, but the World Bank estimates that
it is increasing over time. Consistent with rates of maternal mortality, SMM
rates are higher in low- and middle-income countries (LMICs) than in high-income
countries (HICs). SEVERE MATERNAL MORBIDITY IN HIGH-INCOME COUNTRIES: Since the
WHO recommended that HICs with low maternal mortality ratios begin to examine SMM
to identify systems failures and intervention priorities, researchers in many
HICs have turned their attention to SMM. Where surveillance has been conducted,
the most common etiologies of SMM have been major obstetric hemorrhage and
hypertensive disorders. Of the countries that have conducted SMM reviews, the
most common preventable factors were provider-related, specifically failure to
identify "high risk" status, delays in diagnosis, and delays in treatment. SEVERE
MATERNAL MORBIDITY IN LOW AND MIDDLE INCOME COUNTRIES: The highest burden of SMM
is in Sub-Saharan Africa, where estimates of SMM are as high as 198 per 1000 live
births. Hemorrhage and hypertensive disorders are the leading conditions
contributing to SMM across all regions. Case reviews are rare, but have revealed
patterns of substandard maternal health care and suboptimal use of evidence-based
strategies to prevent and treat morbidity. EFFECTS OF SMM ON DELIVERY OUTCOMES
AND INFANTS: Severe maternal morbidity not only puts the woman's life at risk,
her fetus/neonate may suffer consequences of morbidity and mortality as well.
Adverse delivery outcomes occur at a higher frequency among women with SMM.
Reducing preventable severe maternal morbidity not only reduces the potential for
maternal mortality but also improves the health and well-being of the newborn.
CONCLUSION: Increasing global maternal morbidity is a failure to achieve broad
public health goals of improved women's and infants' health. It is incumbent upon
all countries to implement surveillance initiatives to understand the burden of
severe morbidity and to implement review processes for assessing potential
preventability.
PMID- 29945658
TI - iPSC-derived familial Alzheimer's PSEN2 N141I cholinergic neurons exhibit
mutation-dependent molecular pathology corrected by insulin signaling.
AB - BACKGROUND: Type 2 diabetes (T2D) is a recognized risk factor for the development
of cognitive impairment (CI) and/or dementia, although the exact nature of the
molecular pathology of T2D-associated CI remains obscure. One link between T2D
and CI might involve decreased insulin signaling in brain and/or neurons in
either animal or postmortem human brains as has been reported as a feature of
Alzheimer's disease (AD). Here we asked if neuronal insulin resistance is a cell
autonomous phenomenon in a familial form of AD. METHODS: We have applied a newly
developed protocol for deriving human basal forebrain cholinergic neurons (BFCN)
from skin fibroblasts via induced pluripotent stem cell (iPSC) technology. We
generated wildtype and familial AD mutant PSEN2 N141I (presenilin 2) BFCNs and
assessed if insulin signaling, insulin regulation of the major AD proteins Abeta
and/or tau, and/or calcium fluxes is altered by the PSEN2 N141I mutation.
RESULTS: We report herein that wildtype, PSEN2 N141I and CRISPR/Cas9-corrected
iPSC-derived BFCNs (and their precursors) show indistinguishable insulin
signaling profiles as determined by the phosphorylation of canonical insulin
signaling pathway molecules. Chronic insulin treatment of BFCNs of all genotypes
led to a reduction in the Abeta42/40 ratio. Unexpectedly, we found a CRISPR/Cas9
correctable effect of PSEN2 N141I on calcium flux, which could be prevented by
chronic exposure of BFCNs to insulin. CONCLUSIONS: Our studies indicate that the
familial AD mutation PSEN2 N141I does not induce neuronal insulin resistance in a
cell autonomous fashion. The ability of insulin to correct calcium fluxes and to
lower Abeta42/40 ratio suggests that insulin acts to oppose an AD
pathophysiology. Hence, our results are consistent with a potential physiological
role for insulin as a mediator of resilience by counteracting specific metabolic
and molecular features of AD.
PMID- 29945659
TI - CpG island composition differences are a source of gene expression noise
indicative of promoter responsiveness.
AB - BACKGROUND: Population phenotypic variation can arise from genetic differences
between individuals, or from cellular heterogeneity in an isogenic group of cells
or organisms. The emergence of gene expression differences between genetically
identical cells is referred to as gene expression noise, the sources of which are
not well understood. RESULTS: In this work, by studying gene expression noise
between multiple cell lineages and mammalian species, we find consistent evidence
of a role for CpG islands as sources of gene expression noise. Variation in noise
among CpG island promoters can be partially attributed to differences in island
size, in which short islands have noisier gene expression. Building on these
findings, we investigate the potential for short CpG islands to act as fast
response elements to environmental stimuli. Specifically, we find that these
islands are enriched amongst primary response genes in SWI/SNF-independent
stimuli, suggesting that expression noise is an indicator of promoter
responsiveness. CONCLUSIONS: Thus, through the integration of single-cell RNA
expression profiling, chromatin landscape and temporal gene expression dynamics,
we have uncovered a role for short CpG island promoters as fast response
elements.
PMID- 29945660
TI - Food insecurity and nutritional status of preconception women in a rural
population of North Karnataka, India.
AB - BACKGROUND: As per the World Health Organization, the nutritional status of women
of reproductive age is important, as effects of undernutrition are propagated to
future generations. More than one-third of Indian women in the reproductive age
group are in a state of chronic nutritional deficiency during the preconception
period leading to poor health and likely resulting in low birth weight babies.
This study was aimed to assess the food insecurity and nutritional status of
preconception women in a rural population of north Karnataka. METHODS: A total of
770 preconception women were enrolled across a district in Karnataka from
selected primary health centre areas by a cluster sampling method. Data on
socioeconomic status, food insecurity and obstetric history were collected by
trained research assistants, interviewing women at home. In half of the
participants, a 1 day 24 -hour dietary recalls were conducted by dietary
assistants to assess the dietary intakes. Anthropometric measurements and
haemoglobin estimation were carried out at the health centres. RESULTS: In the
present study, a majority of the participants (64.8%) belonged to the lower socio
economic classes and the prevalence of food insecurity was 27.4%. A majority of
the participants had mild (15.5%) to moderate (78.6%) anaemia. About one-third of
the participants (36.6%) were underweight. Significant associations were found
between socio-economic status and anaemia (p = 0.0006) and between food
insecurity and anaemia (p = 0.0001). CONCLUSION: The nutritional status of
preconception women was poor and anemia was more prevalent in low-socioeconomic
and food insecure population.
PMID- 29945661
TI - Carbohydrate status in patients with phenylketonuria.
AB - BACKGROUND: In patients with phenylketonuria (PKU), a low-phenylalanine (Phe)
diet supplemented with low-protein foods and a Phe-free amino acid mixture favors
a dietary intake rich in carbohydrates, but little is known about how these
molecules are metabolized in this setting. The objective of the present study was
to analyze carbohydrate metabolism in patients with hyperphenylalaninemia.
METHODS: We conducted a multicenter cross-sectional study to investigate
biochemical markers of basal and postprandial carbohydrate metabolism in PKU
patients according to age, Phe tolerance, waist circumference and body mass index
(BMI), diet, tetrahydrobiopterin (BH4) supplementation, and adherence to
treatment. Basal biomarkers and anthropometric parameters were also evaluated in
patients with mild hyperphenylalaninemia (MHPA) and in healthy controls. RESULTS:
A total of 83 patients aged 4-52 years were studied; 68.7% had PKU and 31.3% had
MHPA. 68 healthy controls of similar sex and age were also evaluated Metabolic
control was adequate in 71.9% of PKU patients. Fasting glucose levels (mean 80.77
+/- 8.06 mg/dL) were high in just one patient, but fasting insulin levels, with a
mean of 12.74 +/- 8.4 mIU/L, were altered in 15 PKU patients (26.3%) and markedly
higher than in patients with MPHA (p = 0.035). Fasting insulin levels and
Homeostasis Model Assessment Insulin Resistance (HOMA-IR) were significantly
higher than in healthy controls and correlated with body mass index, waist
circumference, age, and also showed statistically significant differences
according to diagnosis and Phe tolerance (p < 0.05). Patients under BH4 therapy
had lower insulin levels and HOMA-IR. A higher mean carbohydrate intake from AA
mixtures was observed in classic PKU patients. The caloric intake in the form of
carbohydrates was also higher in PKU than MHPA patients (p = 0.038) and it was
correlated with basal insulin (rho = 0.468, p = 0.006), HOMA-IR (rho = 0.423, p =
0.02), BMI (rho 0.533, p = 0.002), and waist circumference (rho 0.584, p =
0.0007). CONCLUSIONS: This study shows that PKU patients are at risk of
carbohydrate intolerance and insulin resistance, more evident in adults and
overweight patients, probably related to their higher caloric intake in form
carbohydrate content. A higher dependency of AA mixtures was demonstrated in PKU
patients.
PMID- 29945663
TI - Stanford type B aortic dissection is more frequently associated with coronary
artery atherosclerosis than type A.
AB - BACKGROUND: The relationship between aortic dissection and coronary artery
disease is not clear. The purpose of this study was to clarify the difference in
the rate of coronary artery atherosclerosis between Stanford type A and type B
aortic dissection by reviewing our institutional database. METHODS: One hundred
and forty-five patients (78 males, 67 females; mean age: 60 +/- 12 years)
admitted to our hospital with acute aortic dissection who underwent coronary
angiography during hospitalization from 2000 through 2002 were enrolled in this
study. The background characteristics, coronary risk factors, and coronary
angiography findings (number of significant stenoses, stenoses according to
Bogaty standards, extent index) of patients were compared between type A (Group
A; n = 71) and type B dissection (Group B; N = 74). RESULTS: Significantly more
patients had prior histories of complications from ischemic heart disease in
Group B than in Group A (P = 0.04), with no significant differences in comparison
to other risk factors observed except for hypertension. Significantly (p = 0.005)
more stenoses were observed in Group B (1.54 +/- 0.04) than in Group A (0.38 +/-
0.1). A significantly higher (P < 0.05) index score indicating the severity of
coronary atherosclerosis was observed in Group B (1.49 +/- 0.09) than in Group A
(0.72 +/- 0.07). CONCLUSIONS: Stanford type B acute aortic dissection was
significantly more frequently associated with coronary artery atherosclerosis
than type A.
PMID- 29945664
TI - What happens for informal caregivers during transition to increased levels of
care for the person with dementia? A systematic review protocol.
AB - BACKGROUND: Dementia is a globally prevalent disease that requires ongoing and
increasing levels of care, often provided in the first instance by informal
caregivers. Supporting transitions in informal caregiving in dementia is a
pertinent issue for caregivers, care providers and governments. There is no
existing systematic review that seeks to identify and map the body of literature
regarding the review question: 'What happens for informal caregivers during
transition to increased levels of care for the person with dementia?'
METHODS/DESIGN: ASSIA, CINAHL+, MEDLINE, PsycINFO, SCIE, Social Service Abstracts
and Web of Science will be systematically searched. Specialist dementia research
libraries will be contacted. Reviews identified as relevant during the search
process, their reference lists, and reference lists of accepted papers will be
hand-searched. Qualitative, quantitative and mixed methods studies that seek to
represent the experiences of, or examine the impact upon, informal caregivers
during transition to increased formal care for the person with dementia will be
eligible for inclusion. Synthesis will be segregated into qualitative and
quantitative papers. Findings will be summarised, and the review will be prepared
for publication. DISCUSSION: The review will seek to identify potentially
vulnerable groups in need of support and as such, inform the practice of those
offering support. It will also inform future research by highlighting areas in
which current literature is insubstantial. SYSTEMATIC REVIEW REGISTRATION:
PROSPERO CRD42017067248.
PMID- 29945662
TI - The feasibility of task-sharing the identification, emergency treatment, and
referral for women with pre-eclampsia by community health workers in India.
AB - BACKGROUND: Hypertensive disorders are the second highest direct obstetric cause
of maternal death after haemorrhage, accounting for 14% of maternal deaths
globally. Pregnancy hypertension contributes to maternal deaths, particularly in
low- and middle-income countries, due to a scarcity of doctors providing evidence
based emergency obstetric care. Task-sharing some obstetric responsibilities may
help to reduce the mortality rates. This study was conducted to assess
acceptability by the community and other healthcare providers, for task-sharing
by community health workers (CHW) in the identification and initial care in
hypertensive disorders in pregnancy. METHODS: This study was conducted in two
districts of Karnataka state in south India. A total of 14 focus group
discussions were convened with various community representatives: women of
reproductive age (N = 6), male decision-makers (N = 2), female decision-makers (N
= 3), and community leaders (N = 3). One-to-one interviews were held with medical
officers (N = 2), private healthcare OBGYN specialists (N = 2), senior health
administrators (N = 2), Taluka (county) health officers (N = 2), and
obstetricians (N = 4). All data collection was facilitated by local researchers
familiar with the setting and language. Data were subsequently transcribed,
translated and analysed thematically using NVivo 10 software. RESULTS: There was
strong community support for home visits by CHW to measure the blood pressure of
pregnant women; however, respondents were concerned about their knowledge,
training and effectiveness. The treatment with oral antihypertensive agents and
magnesium sulphate in emergencies was accepted by community representatives but
medical practitioners and health administrators had reservations, and insisted on
emergency transport to a higher facility. The most important barriers for task
sharing were concerns regarding insufficient training, limited availability of
medications, the questionable validity of blood pressure devices, and the ability
of CHW to correctly diagnose and intervene in cases of hypertensive disorders of
pregnancy. CONCLUSION: Task-sharing to community-based health workers has
potential to facilitate early diagnosis of the hypertensive disorders of
pregnancy and assist in the provision of emergency care. We identified some
facilitators and barriers for successful task-sharing of emergency obstetric care
aimed at reducing mortality and morbidity due to hypertensive disorders of
pregnancy.
PMID- 29945665
TI - Availability and use of magnesium sulphate at health care facilities in two
selected districts of North Karnataka, India.
AB - BACKGROUND: Pre-eclampsia and eclampsia are major causes of maternal morbidity
and mortality. Magnesium sulphate is accepted as the anticonvulsant of choice in
these conditions and is present on the WHO essential medicines list and the
Indian National List of Essential Medicines, 2015. Despite this, magnesium
sulphate is not widely used in India for pre-eclampsia and eclampsia. In addition
to other factors, lack of availability may be a reason for sub-optimal usage.
This study was undertaken to assess the availability and use of magnesium
sulphate at public and private health care facilities in two districts of North
Karnataka, India. METHODS: A facility assessment survey was undertaken as part of
the Community Level Interventions for Pre-eclampsia (CLIP) Feasibility Study
which was undertaken prior to the CLIP Trials (NCT01911494). This study was
undertaken in 12 areas of Belagavi and Bagalkote districts of North Karnataka,
India and included a survey of 88 facilities. Data were collected in all
facilities by interviewing the health care providers and analysed using Excel.
RESULTS: Of the 88 facilities, 28 were public, and 60 were private. In the public
facilities, magnesium sulphate was available in six out of 10 Primary Health
Centres (60%), in all eight taluka (sub-district) hospitals (100%), five of eight
community health centres (63%) and both district hospitals (100%). Fifty-five of
60 private facilities (92%) reported availability of magnesium sulphate. Stock
outs were reported in six facilities in the preceding six months - five public
and one private. Twenty-five percent weight/volume and 50% weight/volume
concentration formulations were available variably across the public and private
facilities. Sixty-eight facilities (77%) used the drug for severe pre-eclampsia
and 12 facilities (13.6%) did not use the drug even for eclampsia. Varied dosing
schedules were reported from facility to facility. CONCLUSIONS: Poor availability
of magnesium sulphate was identified in many facilities, and stock outs in some.
Individual differences in usage were identified. Ensuring a reliable supply of
magnesium sulphate, standard formulations and recommendations of dosage schedules
and training may help improve use; and decrease morbidity and mortality due to
pre-eclampsia/ eclampsia. TRIAL REGISTRATION: The CLIP trial was registered with
ClinicalTrials.gov ( NCT01911494 ).
PMID- 29945666
TI - Effect of the dietary polyacetylenes falcarinol and falcarindiol on the gut
microbiota composition in a rat model of colorectal cancer.
AB - OBJECTIVES: (3R)-Falcarinol (FaOH) and (3R,8S)-falcarindiol (FaDOH) have
previously been shown to reduce the number of neoplastic lesions and the growth
rate of polyps in the colon of azoxymethane (AOM) treated rats. Based on previous
investigations, it appears that different mechanisms of actions are involved in
the antineoplastic effect of FaOH and FaDOH. One mechanism of action may be
related to the antibacterial effect of FaOH and FaDOH and thus their effect on
the gut microbiota. This study aimed to determine the effect of FaOH and FaDOH on
gut microbiota composition of AOM treated rats. RESULTS: Azoxymethane treated
rats were fed either a standard rat diet or a rat diet supplemented with FaOH and
FaDOH. The gut microbiota of AOM-induced rats was determined by 16S rRNA gene
amplicon sequencing. Analysis of fecal cecum samples demonstrated a significant
gut microbiota change in rats receiving standard rat diet supplemented with FaOH
and FaDOH compared with the control group that only received the rat diet.
Comparison of the gut microbiota of rats who developed large neoplasms in the
colon with rats without large neoplasms showed that the gut microbiota was
significantly different in rats who developed large colon neoplasms compared to
rats with no macroscopic colon neoplasms.
PMID- 29945668
TI - Correction to: Seroprevalence and determinants of transfusion transmissible
infections among voluntary blood donors in Homabay, Kisumu and Siaya counties in
western Kenya.
AB - Following publication of the original article [1], the authors reported that for
two of the authors, Felix Humwa and Vallarie Opollo, an incorrect affiliation has
been given. In this Correction the incorrect and correct affiliations are listed.
PMID- 29945667
TI - Analysis of novel caudal hindbrain genes reveals different regulatory logic for
gene expression in rhombomere 4 versus 5/6 in embryonic zebrafish.
AB - BACKGROUND: Previous work aimed at understanding the gene regulatory networks
(GRNs) governing caudal hindbrain formation identified morphogens such as
Retinoic Acid (RA) and Fibroblast growth factors (FGFs), as well as transcription
factors like hoxb1b, hoxb1a, hnf1ba, and valentino as being required for
rhombomere (r) r4-r6 formation in zebrafish. Considering that the caudal
hindbrain is relatively complex - for instance, unique sets of neurons are formed
in each rhombomere segment - it is likely that additional essential genes remain
to be identified and integrated into the caudal hindbrain GRN. METHODS: By taking
advantage of gene expression data available in the Zebrafish Information Network
(ZFIN), we identified 84 uncharacterized genes that are expressed in r4-r6. We
selected a representative set of 22 genes and assayed their expression patterns
in hoxb1b, hoxb1a, hnf1b, and valentino mutants with the goal of positioning them
in the caudal hindbrain GRN. We also investigated the effects of RA and FGF on
the expression of this gene set. To examine whether these genes are necessary for
r4-r6 development, we analyzed germline mutants for six of the genes (gas6, gbx1,
sall4, eglf6, celf2, and greb1l) for defects in hindbrain development. RESULTS:
Our results reveal that r4 gene expression is unaffected by the individual loss
of hoxb1b, hoxb1a or RA, but is under the combinatorial regulation of RA together
with hoxb1b. In contrast, r5/r6 gene expression is dependent on RA, FGF, hnf1ba
and valentino - as individual loss of these factors abolishes r5/r6 gene
expression. Our analysis of six mutant lines did not reveal rhombomere or
neuronal defects, but transcriptome analysis of one line (gas6 mutant) identified
expression changes for genes involved in several developmental processes -
suggesting that these genes may have subtle roles in hindbrain development.
CONCLUSION: We conclude that r4-r6 formation is relatively robust, such that very
few genes are absolutely required for this process. However, there are
mechanistic differences in r4 versus r5/r6, such that no single factor is
required for r4 development while several genes are individually required for
r5/r6 formation.
PMID- 29945669
TI - Comparison of the effectiveness between transcutaneous electrical nerve
stimulation, manual acupuncture, and electroacupuncture on tinnitus: study
protocol for a randomized controlled trial.
AB - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) involves a
neuromodulatory effect using electrical stimulation and has been widely used due
to its safety and convenience. It has been used for treating tinnitus for
decades. Acupuncture has also been used for tinnitus and several research studies
have shown that acupuncture can improve a certain kind of tinnitus by stimulating
the somatosensory system. Moreover, several studies have shown the efficacy of
electroacupuncture, which is a combination of acupuncture and electrical
stimulation, for tinnitus. However, the comparative effectiveness of TENS, manual
acupuncture, and electroacupuncture for the treatment of tinnitus has not been
determined previously. Herein, we design a randomized, non-blind clinical trial
to investigate and compare the effects and safety of TENS, manual acupuncture,
and electroacupuncture for tinnitus. METHODS: After screening, 45 patients are
randomly assigned to three groups: (1) patients in the TENS group are treated at
four sites (tender points of masseter and the sternocleidomastoid muscle, in
front of tragus, and mastoid process); (2) the manual acupuncture group patients
are treated at 11 acupoints (TE21, SI19, GB2, TE22, ST7, TE17, GB20 of tinnitus
affected side, and GB20, TE05, KI3 of both sides); (3) electroacupuncture group
patients are treated by using acupuncture as in the manual acupuncture group and
electrical stimulation at TE21, SI19, TE17, and GB20. Patients are treated for
ten sessions, twice a week. The primary outcome measurement is the change of
Tinnitus Handicap Inventory (THI) score between visit 1 and visit 10. The
secondary outcome measurements are the response rate of THI, change in visual
analogue scale associated with the loudness and annoyance of tinnitus, pure-tone
audiometry and speech discrimination, and changes in parameters of heart rate
variability. DISCUSSION: The purpose of this study is to compare the effect of
TENS, manual acupuncture, and electroacupuncture in the auricular area on
tinnitus. If the specific treatment shows a significant effect compared to other
treatments, it could have potential for use in clinical practice as a primary
treatment. TRIAL REGISTRATION: Clinical Research Information Service (CRIS),
KCT0002117 . Registered October 21, 2016. Retrospectively registered.
PMID- 29945670
TI - Acute skin allergy to thermoplastic mask used for patient immobilization during
radiation therapy: a case report.
AB - BACKGROUND: Radiosurgical treatments of brain tumors, vascular malformations, and
functional disorders are more and more frequently used. Gamma Knife irradiation
with the Icon system necessitates the use of a thermoplastic mask for head
immobilization during treatment. Acute cutaneous allergy to thermoplastic masks
has never been reported. CASE PRESENTATION: A 71-year-old Caucasian woman treated
radiosurgically for a sphenoidal meningioma using the Icon Gamma Knife system
developed an acute allergic skin reaction to the thermoplastic mask used for head
immobilization. Corticoids and antihistamine drugs were needed to continue the
radiosurgical procedure to its end. CONCLUSION: Allergic reaction of the skin
during radiosurgery with a thermoplastic mask for head fixation can develop due
to cutaneous contact of the face with the mask.
PMID- 29945672
TI - Crossbow needle therapy of the Miao ethnic minority group for knee
osteoarthritis: study protocol for a randomized controlled trial.
AB - BACKGROUND: Knee osteoarthritis (KOA) is commonly seen and has a high occurrence
in the middle-aged and elderly. It is characterized by the degeneration and
secondary bone hyperplasia of the articular cartilage; the pathologic changes are
irreversible. Therefore, treatment of KOA is mainly focused on relieving pain,
reducing inflammation, improving or restoring joint function, delaying disease
progression, and increasing quality of life. Crossbow needle therapy of the Miao
ethnic minority group is intended for KOA treatment and has been widely used.
Studies of small sample size have seen significant improvement on pain relief,
stiffness, and joint function. METHODS/DESIGN: The trial is a randomized,
multicenter, parallel, non-inferiority study. Three hundred and six patients will
be randomly assigned to a crossbow needle group (n = 153) and an acupuncture
group (n = 153). Patients in each group will receive treatment every other day,
three times a week, 20 times in total. Follow-up will be conducted 15 days and 30
days after treatment. The primary outcome will be the Western Ontario and
McMaster Osteoarthritis Index (WOMAC) score at baseline, the end of treatment,
first follow-up, and second follow-up. The secondary outcomes will include
Lysholm knee score, Japanese Orthopedic Association (JOA) knee score, visual
analogue scale (VAS), and the MOS 36-item short-form health survey (SF-36).
DISCUSSION: The results of the trial will compare the efficacy on KOA between
crossbow needle group and acupuncture group and will be expected to make a
systematic and objective evaluation of crossbow needle therapy. TRIAL
REGISTRATION: ChiCTR, ChiCTR-INR-16008032 . Registered on 12 March 2016.
PMID- 29945671
TI - Pericellular collagen I coating for enhanced homing and chondrogenic
differentiation of mesenchymal stem cells in direct intra-articular injection.
AB - BACKGROUND: Direct intra-articular injection (DIAI) of mesenchymal stem cells
(MSCs) is a promising technique for cartilage repair. However, the repair process
was hindered by the absence of scaffold and poor cell-matrix interactions.
METHODS: In this study, we developed a pericellular collagen I coating (PCC) on
MSCs. The overall performances of MSC-PCC homing, chondrogenic differentiation,
and cartilage regeneration have been comprehensively evaluated in a New Zealand
rabbit model. Firstly, we examined the morphology and physical characteristics of
PCC. Secondly, MSC ex-vivo cartilage slice adhesion and in-vivo cartilage defect
homing were observed using multiscale methods. Thirdly, the precartilage
condensation of cell pellets formed by aggregation of MSCs was examined to
evaluate the cartilage-inducing potential of PCC. Finally, the cartilage
regeneration by DIAI of PCC-coated MSCs was observed and scored macroscopically
and histologically. RESULTS: In general, the cell adhesion and homing assay
revealed that PCC facilitated MSC adhesion on cartilage slices, enhancing MSC
homing and retention to cartilage defect. This increased homing ratio was
accompanied by an increasing cell-cell contact. Compared with naked MSCs, the
cell pellets formed by PCC-coated MSCs exhibited more evident appearance of
condensation. In pellets, cell-cell interaction has been significantly
stimulated, inducing the expression of condensation marker N-cadherin, and
subsequent chondrogenic marker collagen II and aggrecan. By 12 weeks after DIAI,
cartilage defects have been repaired by MSCs to varying degrees. Overall, PCC
significantly enhances the quality of cartilage regeneration judging from
macroscopic observation, ICRS score, histological examination, and collagen type
I, II, and X immunohistochemical staining. CONCLUSIONS: The capacity and
viability of MSCs can be enhanced by collagen I coating, which provides cues for
enhancing cell homing and differentiation. Our method provides a novel strategy
for stem cell therapy.
PMID- 29945673
TI - Exploring and adjusting for potential learning effects in ROLARR: a randomised
controlled trial comparing robotic-assisted vs. standard laparoscopic surgery for
rectal cancer resection.
AB - BACKGROUND: Commonly in surgical randomised controlled trials (RCT) the
experimental treatment is a relatively new technique which the surgeons may still
be learning, while the control is a well-established standard. This can lead to
biased comparisons between treatments. In this paper we discuss the
implementation of approaches for addressing this issue in the ROLARR trial, and
points of consideration for future surgical trials. METHODS: ROLARR was an
international, randomised, parallel-group trial comparing robotic vs.
laparoscopic surgery for the curative treatment of rectal cancer. The primary
endpoint was conversion to open surgery (binary). A surgeon inclusion criterion
mandating a minimum level of experience in each technique was incorporated.
Additionally, surgeon self-reported data were collected periodically throughout
the trial to capture the level of experience of every participating surgeon.
Multi-level logistic regression adjusting for operating surgeon as a random
effect is used to estimate the odds ratio for conversion to open surgery between
the treatment groups. We present and contrast the results from the primary
analysis, which did not account for learning effects, and a sensitivity analysis
which did. RESULTS: The primary analysis yields an estimated odds ratio
(robotic/laparoscopic) of 0.614 (95% CI 0.311, 1.211; p = 0.16), providing
insufficient evidence to conclude superiority of robotic surgery compared to
laparoscopic in terms of the risk of conversion to open. The sensitivity analysis
reveals that while participating surgeons in ROLARR were expert at laparoscopic
surgery, some, if not all, were still learning robotic surgery. The treatment
effect odds ratio decreases by a factor of 0.341 (95% CI 0.121, 0.960; p = 0.042)
per unit increase in log-number of previous robotic operations performed by the
operating surgeon. The odds ratio for a patient whose operating surgeon has the
mean experience level in ROLARR - 152.46 previous laparoscopic, 67.93 previous
robotic operations - is 0.40 (95% CI 0.168, 0.953; p = 0.039). CONCLUSIONS: In
this paper we have demonstrated the implementation of approaches for accounting
for learning in a practical example of a surgery RCT analysis. The results
demonstrate the value of implementing such approaches, since we have shown that
without them the ROLARR analysis would indeed have been confounded by the
learning effects. TRIAL REGISTRATION: International Standard Randomised
Controlled Trial Number (ISRCTN) registry, ID: ISRCTN80500123. Registered on 27
May 2010.
PMID- 29945675
TI - Successful treatment following early recognition of a case of Fournier's scrotal
gangrene after a perianal abscess debridement: a case report.
AB - BACKGROUND: Fournier's gangrene is an acute surgical emergency characterized by
high mortality rates ranging from approximately 13% to 45%. Therefore, aggressive
multidisciplinary management is necessary. CASE PRESENTATION: A 29-year-old Asian
man who had undergone surgical debridement at another hospital to treat a
perianal abscess 5 days earlier was admitted to our hospital for severe scrotal
and perianal pain, swelling, and high fever. A physical examination revealed a
perianal abscess. Furthermore, the scrotum was gangrenous and exhibited extensive
cellulitis in the perineum and bilateral inguinal area. Crepitations between the
skin and fascia were palpable. A diagnosis of Fournier's gangrene was made. The
patient was treated with immediate surgical debridement under general anesthesia.
He received broad-spectrum antibiotics, and debridement was repeated until the
wound exhibited healthy granulation. Because both testes were severely exposed,
they were transpositioned back into the scrotum 1 week after surgery. The patient
was discharged on the 11th postoperative day. CONCLUSIONS: The mainstay of
treatment for Fournier's gangrene should include fluid resuscitation, broad
spectrum antibiotic therapy, intensive care, nutritional support, and early
aggressive surgical debridement of all necrotic tissue.
PMID- 29945674
TI - Treatment of voluminous and complicated superficial slow-flow vascular
malformations with sirolimus (PERFORMUS): protocol for a multicenter phase 2
trial with a randomized observational-phase design.
AB - BACKGROUND: Slow-flow superficial vascular malformations (VMs) are rare
congenital anomalies that can be responsible for pain and functional impairment.
Currently, we have no guidelines for their management, which can involve physical
bandages, sclerotherapy, surgery, anti-inflammatory or anti-coagulation drugs or
no treatment. The natural history is progressive and worsening. Mammalian target
of rapamycin (mTOR) is a serine/threonine kinase that acts as a master switch in
cell proliferation, apoptosis, metabolism and angio/lymphangiogenesis. Sirolimus
directly inhibits the mTOR pathway, thereby inhibiting cell proliferation and
angio/lymphangiogenesis. Case reports and series have reported successful use of
sirolimus in children with different types of vascular anomalies, with
heterogeneous outcomes. OBJECTIVE: The objective of this trial is to evaluate the
efficacy and safety of sirolimus in children with complicated superficial slow
flow VMs. METHODS/DESIGN: This French multicenter randomized observational-phase,
phase 2 trial aims to include 50 pediatric patients 6 to 18 years old who have
slow-flow (lymphatic, venous or lymphatico-venous) voluminous complicated
superficial VM. Patients will be followed up for 12 months. All patients will
start with an observational period (no treatment). Then at a time randomly
selected between month 4 and month 8, they will switch to the experimental period
(switch time), when they will receive sirolimus until month 12. Each child will
undergo MRI 3 times: at baseline, at the switch time, and at month 12. For both
periods (observational and treatment), we will calculate the relative change in
volume of the VM divided by the study period duration. This relative change
weighted by the study period duration will constitute the primary endpoint. VM
will be measured by MRI images, which will be centralized and interpreted by the
same radiologist who will be blinded to the study period. Hence, each patient
will be his/her own control. Secondary outcomes will include assessment of safety
and efficacy by viewing standardized digital photographs and according to the
physician, the patient or proxy; impact on quality of life; and evolution of
biological makers (coagulation factors, vascular endothelial growth factor,
tissue factor). DISCUSSION: The main benefit of the study will be to resolve
uncertainty concerning the efficacy of sirolimus in reducing the volume of VMs
and limiting related complications and the safety of the drug in children with
slow-flow VMs. This trial design is interesting in these rare conditions because
all included patients will have the opportunity to receive the drug and the
physician can maintain it after the end of the protocol if is found efficient
(which would not be the case in a classical cross-over study). TRIAL
REGISTRATION: ClinicalTrials.gov Identifier: NCT02509468 , first received: 28
July 2015. EU Clinical Trials Register EudraCT Number: 2015-001096-43.
PMID- 29945676
TI - Reversible splenial lesion syndrome associated with dengue fever: a case report.
AB - BACKGROUND: Dengue virus infection in humans can lead to a wide range of clinical
manifestations, from mild fever to potentially fatal dengue shock syndrome. The
incidence of dengue fever is on the rise in tropical countries. Due to the
increasing incidence of dengue fever worldwide, atypical manifestations of the
disease are increasingly reported. In this article we report a patient with
dengue haemorrhagic fever who presented with reversible splenial lesion syndrome.
CASE PRESENTATION: A 24-year-old Sri Lankan man who presented with fever and
confusion was eventually diagnosed to have reversible splenial lesion syndrome
based on brain imaging. Clinical, serological and haematological parameters
confirmed a diagnosis of dengue haemorrhagic fever. His presentation, assessment,
and management are described in this case report. CONCLUSION: Reversible splenial
lesion syndrome is a condition which is radiologically characterized by
reversible lesion in the splenium of the corpus callosum. It is associated with
infectious and non-infectious aetiologies. This case report highlights the
occurrence of reversible splenial lesion syndrome as a presenting feature of the
expanding list of unusual neurological manifestations of dengue infection.
PMID- 29945677
TI - Heterosexual men who purchase sex and attended an STI clinic in Israel:
characteristics and sexual behavior.
AB - BACKGROUND: Commercial sex shares a role in HIV and sexually transmitted
infections (STI) transmission. Men who pay for sex (MPS) may transmit HIV/STI to
other populations which are low-risk. This study aimed to test our hypothesis
that MPS engage in high-risk sexual behaviors associated with HIV/STI
transmission more so than non-MPS. METHODS: This cross-sectional study included
heterosexual men who attended an STI clinic between 2003 and 2010. Demographic,
clinical, behavioral and laboratory data were compared between MPS and non-MPS to
identify factors associated with high-risk sexual behavior and STI-burden.
RESULTS: Of the first visits of 6156 heterosexual men who attended the STI-clinic
during the study period, 1649 (26.7%) were MPS. MPS were more commonly older,
married and non-Israeli born compared with non-MPS. MPS were more likely to
engage in risk-behaviors associated with HIV/STI-transmission, including a
greater number of lifetime sexual partners, substance use and previous STI
diagnoses. Determinants associated with STI-diagnoses at the current visit
included being non-Israeli born, presenting with STI symptoms, reporting a
greater number of lifetime sexual partners and having sexual encounters with non
Israeli individuals. CONCLUSIONS: Approximately 25% of all men who attended the
clinic were MPS. They were more likely to engage in risk-behaviors associated
with HIV/STI transmission compared to non-MPS. These findings highlight the need
to establish interventions for MPS that both continue to encourage condom use and
address the potential perils pertaining to risky sexual behaviors.
PMID- 29945678
TI - Construction and characterization of thymidine auxotrophic (DeltathyA)
recombinant Lactobacillus casei expressing bovine lactoferricin.
AB - BACKGROUND: Lactobacillus casei (L. casei) is well known for its probiotic
property in human and animals. Lactoferricin (Lfcin) polypeptide can effectively
modulate host immune responses and have antimicrobial activity in vivo and in
vitro. In order to develop a food-grade L. casei system constitutively expressing
bovine Lfcin, this study constructed a thymidine auxotrophy (DeltathyA)
recombinant L. casei. RESULTS: Based on the thymidylate synthase gene (thyA)
insert site, LFEC(Lfcin expression cassette)was inserted into L. casei genome
through homologous recombination, successfully expressed and could be stably
inherited. The recombinant L. casei, DeltathyA L. casei-LFEC, is sensitive to
chloramphenicol and limited when cultured without thymine. Meanwhile, DeltathyA
L. casei-LFEC has both good antibacterial activity against Escherichia coli and
Staphylococcus aureus and antiviral activity against porcine epidemic diarrhea
virus (PEDV). CONCLUSIONS: We successfully constructed a recombinant L. casei
strain expressing Lfcin, DeltathyA L. casei-LFEC, which could only survive in the
presence of thymine, and had excellent antimicrobial and antiviral activity with
good genetic stability and sensitivity. This research provides a cost-effective
alternative to the antibiotics with additional biological functions and wider
applicability prospect. Using DeltathyA as the selectable mark instead of
antibiotic to construct genetic engineering L.casei provides a safe and effective
approach of feed additives in livestock raising.
PMID- 29945679
TI - Bovine respiratory syncytial virus seroprevalence and risk factors in non
vaccinated dairy cattle herds in Brazil.
AB - BACKGROUND: The cattle industry is one of the most important Brazilian
agribusiness sectors and is a strong contributor to the national economy.
Annually about 44.6 million calves are bred, which makes the optimal management
of these animals extremely important. Several diseases can affect the initial
stages of the bovine production chain, being the bovine respiratory syncytial
virus (BRSV) one of the most relevant pathogens. This study aimed to characterize
the epidemiology of BRSV infection in dairy cattle herds of Sao Paulo State,
Brazil, using serological and risk factors analyses. For that, 1243 blood samples
were collected of animals from 26 farms and a questionnaire about possible risk
factors for BRSV prevalence was performed. The obtained blood sera were analyzed
using virus neutralization test (VNT). RESULTS: VNT results showed high BRSV
prevalence in dairy cattle herds, reaching 79.5% of seropositivity. The BRSV
seroprevalence among studied farms ranged from 40 to 100%. The analysis of risk
factors indicated that the age group and the occurrence of coinfection with
bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus 1 (BVDV-1) should
be associated with a higher prevalence of BRSV, while natural suckling was
considered a protective factor. CONCLUSIONS: The study showed that adult animals
over 1 year old are an important risk factor for the high seroprevalence of BRSV
in herds. The high BRSV prevalence associated with BoHV-1 and BVDV-1 suggests
that biosecurity measures should be applied in order to reduce viral
dissemination. Additionally, the natural suckling may be an important management
to protect calves from high BRSV seroprevalence.
PMID- 29945681
TI - Monte Carlo verification of radiotherapy treatments with CloudMC.
AB - BACKGROUND: A new implementation has been made on CloudMC, a cloud-based platform
presented in a previous work, in order to provide services for radiotherapy
treatment verification by means of Monte Carlo in a fast, easy and economical
way. A description of the architecture of the application and the new
developments implemented is presented together with the results of the tests
carried out to validate its performance. METHODS: CloudMC has been developed over
Microsoft Azure cloud. It is based on a map/reduce implementation for Monte Carlo
calculations distribution over a dynamic cluster of virtual machines in order to
reduce calculation time. CloudMC has been updated with new methods to read and
process the information related to radiotherapy treatment verification: CT image
set, treatment plan, structures and dose distribution files in DICOM format. Some
tests have been designed in order to determine, for the different tasks, the most
suitable type of virtual machines from those available in Azure. Finally, the
performance of Monte Carlo verification in CloudMC is studied through three real
cases that involve different treatment techniques, linac models and Monte Carlo
codes. RESULTS: Considering computational and economic factors, D1_v2 and G1
virtual machines were selected as the default type for the Worker Roles and the
Reducer Role respectively. Calculation times up to 33 min and costs of 16 ? were
achieved for the verification cases presented when a statistical uncertainty
below 2% (2sigma) was required. The costs were reduced to 3-6 ? when uncertainty
requirements are relaxed to 4%. CONCLUSIONS: Advantages like high computational
power, scalability, easy access and pay-per-usage model, make Monte Carlo cloud
based solutions, like the one presented in this work, an important step forward
to solve the long-lived problem of truly introducing the Monte Carlo algorithms
in the daily routine of the radiotherapy planning process.
PMID- 29945680
TI - A Prospective Study of Causes of Illness and Death in Preterm Infants in
Ethiopia: The SIP Study Protocol.
AB - BACKGROUND: With nearly 15 million annual preterm births globally, preterm birth
is the most common cause of neonatal death. Forty to 60 % of neonatal deaths are
directly or indirectly associated with preterm mortality. As countries aim to
meet the Sustainable Development Goals to reduce neonatal mortality, significant
reductions in preterm mortality are needed. This study aims to identify the
common causes of preterm illness and their contribution to preterm mortality in
low-resource settings. This article will describe the methods used to undertake
the study. METHODS: This is a prospective, multi-centre, descriptive clinical
study. Socio-demographic, obstetric, and maternal factors, and clinical and
laboratory findings will be documented. The major causes of preterm mortality
will be identified using clinical, laboratory, imaging, and autopsy methods and
use the national Ethiopian guidelines on management of preterm infants including
required investigations to reach final diagnoses. The study will document the
clinical and management protocols followed in these settings. The approach
consists of clinical examinations and monitoring, laboratory investigations, and
determination of primary and contributory causes of mortality through both
clinical means and by post-mortem examinations. An independent panel of experts
will validate the primary and contributory causes of mortality. To obtain the
estimated sample size of 5000 preterm births, the study will be undertaken in
five hospitals in three regions of Ethiopia, which are geographically distributed
across the country. All preterm infants who are either born or transferred to
these hospitals will be eligible for the study. Three methods (last menstrual
period, physical examination using the New Ballard Score, and ultrasound) will be
used to determine gestational age. All clinical procedures will be conducted per
hospital protocol and informed consent will be taken from parents or caretakers
prior to their participation in the study as well as for autopsy if the infant
dies. DISCUSSION: This study will determine the major causes of death and illness
among hospitalized preterm infants in a low-resource setting. The result will
inform policy makers and implementers of areas that can be prioritized in order
to contribute to a significant reduction in neonatal mortality.
PMID- 29945683
TI - Caution needs to be taken when assigning transcription start sites to ends of
protein-coding genes: a rebuttal.
AB - Naturally occurring stress-induced transcriptional readthrough is a recently
discovered phenomenon, in which stress conditions lead to dramatic induction of
long transcripts as a result of transcription termination failure. In 2015, we
reported the induction of such downstream of gene (DoG) containing transcripts
upon osmotic stress in human cells, while others observed similar transcripts in
virus-infected and cancer cells. Using the rigorous methodology Cap-Seq, we
demonstrated that DoGs result from transcriptional readthrough, not de novo
initiation. More recently, we presented a genome-wide comparison of NIH3T3 mouse
cells subjected to osmotic, heat, and oxidative stress and concluded that massive
induction of transcriptional readthrough is a hallmark of the mammalian stress
response. In their recent letter, Huang and Liu in contrast claim that DoG
transcripts result from novel transcription initiation near the ends of genes.
Their conclusions rest on analyses of a publicly available transcription start
site (TSS-Seq) dataset from unstressed NIH3T3 cells. Here, we present evidence
that this dataset identifies not only true transcription start sites, TSSs, but
also 5'-ends of numerous snoRNAs, which are generally processed from introns in
mammalian cells. We show that failure to recognize these erroneous assignments in
the TSS-Seq dataset, as well as ignoring published Cap-Seq data on TSS mapping
during osmotic stress, have led to misinterpretation by Huang and Liu. We
conclude that, contrary to the claims made by Huang and Liu, TSS-Seq reads near
gene ends cannot explain the existence of DoGs, nor their stress-mediated
induction. Rather it is, as we originally demonstrated, transcriptional
readthrough that leads to the formation of DoGs.
PMID- 29945684
TI - Understanding the effect of ultraviolet light intensity on disinfection
performance through the use of ultraviolet measurements and simulation.
AB - We measured the disinfection of MRSA and Clostridium difficile spores using an
ultraviolet C (UV-C) device, and we correlated those results to measurements and
computer simulations of UV-C surface intensity. The results demonstrate both
large differences in UV light intensity across various surfaces and how this
leads to significant differences in disinfection.
PMID- 29945682
TI - Effects of neuromodulation on cognitive performance in individuals exhibiting
addictive behaviour: a systematic review protocol.
AB - BACKGROUND: Individuals with substance use and addictive disorders often display
greater risk-taking behaviour, higher impulsivity, and altered reward processing
compared to individuals without these disorders. While it is not known whether
cognitive biases precede or result from addictive behaviour, they likely
influence addiction-related decision-making, and may facilitate pathological
behaviour. There is evidence that cognitive functions-including those shown to be
altered in substance use and addictive disorders-can be influenced by
neuromodulation techniques (specifically, transcranial direct current stimulation
and transcranial magnetic stimulation). Much of this work has been conducted in
healthy populations, however, making it unclear whether these methods can be used
effectively to modulate cognitive functioning in individuals with substance use
and addictive disorders. The purpose of the current review is to shed light on
the potential effectiveness and feasibility of neuromodulation as a means to
improve cognitive deficits in substance use disorders. METHODS: The review will
identify and evaluate studies that have examined the effects of transcranial
direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) on
cognitive task performance in individuals with chronic substance use or
dependence. Relevant studies will be identified through searches in PubMed,
PsycINFO, Scopus, and Embase, and narrative review will be used to explore
evidence that these techniques can be used successfully to modulate cognitive
performance in populations exhibiting addictive behaviour. Assessing individual
cognitive domains in turn (e.g. risk-taking, impulsivity, attention), we will
critically evaluate the validity and reliability of relevant studies and draw
conclusions about the strength of evidence for effective use of neuromodulation
in that domain. This protocol is not yet registered with PROSPERO. DISCUSSION: To
determine whether neuromodulation holds promise as an effective treatment for
neurocognitive deficits in substance use and addictive disorders, it is essential
to look carefully at previous studies using this approach in addiction samples.
This review will provide an objective and informative description of what is
currently known about the efficacy of these techniques, shed light on the
feasibility and potential challenges of using neuromodulation in individuals who
exhibit addictive behaviour, and identify the most valuable next steps for future
research.
PMID- 29945685
TI - Detection of influenza myocarditis using national healthcare safety network
surveillance definitions accounting for fever in older adults.
PMID- 29945686
TI - Underlying trend, seasonality, prediction, forecasting and the contribution of
risk factors: an analysis of globally reported cases of Middle East Respiratory
Syndrome Coronavirus - CORRIGENDUM.
PMID- 29945687
TI - Prevalence of human papillomavirus types in North and Central regions of Mexico.
AB - Human papillomavirus (HPV) is a DNA virus linked to mucosal and cutaneous
carcinogenesis. More than 200 different HPV types exist. We carried out a
transversal study to investigate the prevalence of HPV types in two regions of
Mexico. A total of 724 genital and non-genital samples from women (F) and men (M)
were studied; 241 (33%) from North-Eastern (NE) and 483 (66%) from South-Central
(SC) Mexico. The overall prevalence was 87%. In genital lesions from females, the
NE group showed a prevalence of HPV types 16 (37%), 6 (13%), 59 (6%), 11, 18 and
66 (5.4% each); and the SC group showed types 6 (17%), 16 (15%), 11 (14.5%), 18
(12%) and 53 (6%). In the genital lesions from males, NE group showed types 16
(38%), 6 (21%), 11 (13%) and 59 plus 31 (7.5%) and the SC group showed types 6
(25%), 11 (22%), 18 (17%) and 16 (11.5%). When the two regions were compared, a
higher prevalence of low-risk HPV 6 and 11 was found in the SC region and of high
risk HPV 59, 31 and 66 (the latter can also be present in benign lesions) in the
NE region. Our findings complement efforts to understand HPV demographics as a
prerequisite to guide and assess the impact of preventive interventions.
PMID- 29945688
TI - Fire Disaster Readiness: Preparation for the Evacuation of Medical Facilities
During Fires in Haifa, Israel, 2016.
AB - When a fire occurs, there is little time to escape. In less than 30 seconds, a
fire can rage out of control, filling the area with heat and toxic thick smoke
(Purdue University Fire Department, 2017; http://www.purdue.edu/ehps/fire/fire
101.html.) In 2010, following the successful evacuation of Maale Ha'Carmel Mental
Health Center during a raging forest fire in the area, a comprehensive
investigation was performed to evaluate the management of the evacuation process
and to systematically elicit lessons learned from the incident. In 2016, a forest
fire erupted in the same geographic area that required the evacuation of Fliman
Geriatric Rehabilitation Hospital, and methodical debriefing identified the
strengths and weaknesses of the evacuation process in that hospital. The lessons
learned from the evacuation of these two health care facilities, which were at
the focus of major fires in Israel in 2010 and in 2016, are presented. (Disaster
Med Public Health Preparedness. 2018; page 1 of 5).
PMID- 29945689
TI - Different latent class models were used and evaluated for assessing the accuracy
of campylobacter diagnostic tests: overcoming imperfect reference standards?
AB - In the absence of perfect reference standard, classical techniques result in
biased diagnostic accuracy and prevalence estimates. By statistically defining
the true disease status, latent class models (LCM) constitute a promising
alternative. However, LCM is a complex method which relies on parametric
assumptions, including usually a conditional independence between tests and might
suffer from data sparseness. We carefully applied LCMs to assess new
campylobacter infection detection tests for which bacteriological culture is an
imperfect reference standard. Five diagnostic tests (culture, polymerase chain
reaction and three immunoenzymatic tests) of campylobacter infection were
collected in 623 patients from Bordeaux and Lyon Hospitals, France. Their
diagnostic accuracy were estimated with standard and extended LCMs with a
thorough examination of models goodness-of-fit. The model including a residual
dependence specific to the immunoenzymatic tests best complied with LCM
assumptions. Asymptotic results of goodness-of-fit statistics were substantially
impaired by data sparseness and empirical distributions were preferred. Results
confirmed moderate sensitivity of the culture and high performances of
immunoenzymatic tests. LCMs can be used to estimate diagnostic tests accuracy in
the absence of perfect reference standard. However, their implementation and
assessment require specific attention due to data sparseness and limitations of
existing software.
PMID- 29945690
TI - Does government expenditure reduce inequalities in infant mortality rates in low-
and middle-income countries?: A time-series, ecological analysis of 48 countries
from 1993 to 2013.
AB - Inequalities in infant mortality rates (IMRs) are rising in some low- and middle
income countries (LMICs) and decreasing in others, but the explanation for these
divergent trends is unclear. We investigate whether government expenditures and
redistribution are associated with reductions in inequalities in IMRs. We
estimated country-level fixed-effects panel regressions for 48 LMICs (142 country
observations). Slope and Relative Indices of Inequality in IMRs (SII and RII)
were calculated from Demographic and Health Surveys between 1993 and 2013. RII
and SII were regressed on government expenditure (total, health and non-health)
and redistribution, controlling for gross domestic product (GDP), private health
expenditures, a democracy indicator, country fixed effects and time. Mean SII and
RII was 39.12 and 0.69, respectively. In multivariate models, a 1 percentage
point increase in total government expenditure (% of GDP) was associated with a
decrease in SII of -2.468 [95% confidence intervals (CIs): -4.190, -0.746] and
RII of -0.026 (95% CIs: -0.048, -0.004). Lower inequalities were associated with
higher non-health government expenditure, but not higher government health
expenditure. Associations with inequalities were non-significant for GDP,
government redistribution, and private health expenditure. Understanding how non
health government expenditure reduces inequalities in IMR, and why health
expenditures may not, will accelerate progress towards the Sustainable
Development Goals.
PMID- 29945691
TI - Campylobacter control measures in indoor broiler chicken: critical re-assessment
of cost-utility and putative barriers to implementation.
AB - As campylobacteriosis is one of the most important foodborne infections, a
European Union (EU)-27 level cost-effectiveness model has been developed on the
socio-economic costs and benefits of applying certain control measures for the
reduction of Campylobacter in broiler meat. This is expected to be a gold
standard for food safety policymakers in the EU; hence, the validity of its
modelling assumptions is essential. The authors of the present paper conducted an
independent review of model input parameters on health and economic burden and
found that the model most probably overestimated the burden of human
campylobacteriosis. A discounted, quality-adjusted life year (QALY)-based
European estimate has been developed for human campylobacteriosis and resulted in
15.23 QALY loss per 1000 human gastroenteritis cases. Country-specific cost of
illness estimates have been developed for various countries in the EU-27. Based
on these model adaptations, a selected Campylobacter control strategy was re
assessed and its high cost-effectiveness was confirmed at the EU level, and also
in all but three Member States. Bacteriocin treatment or vaccination of the
animals, two alternative control measures were also re-evaluated, and these
strategies seemed to be far less cost-effective than the investigated strategy.
Putative barriers to the rapid implementation of the investigated Campylobacter
control strategy are discussed, and potential solutions are proposed. Further
research is required on stakeholder perspectives pertaining to the realistic
barriers and implementation opportunities.
PMID- 29945692
TI - Analysis of Bisphenol A, Alkylphenols, and Alkylphenol Ethoxylates in NIST SRM
2585 and Indoor House Dust by Gas Chromatography-Tandem Mass Spectrometry
(GC/MS/MS).
AB - Background: Ingestion of house dust has been demonstrated to be an important
exposure pathway to several contaminants in young children. These compounds
include bisphenol A (BPA), alkylphenols (APs), and alkylphenol ethoxylates
(APEOs). Analysis of these compounds in house dust is challenging because of the
complex composition of the sample matrix. Objective: The objective was to develop
a simple and sensitive method to measure BPA, APs, and APEOs in indoor house
dust. Methods: An integrated method that involved solvent extraction using
sonication, sample cleanup by solid-phase extraction, derivatization by 2,2,2
trifluoro-N-methyl-N-(trimethylsilyl)acetamide, and analysis by GC coupled with
tandem MS was developed for the simultaneous determination of BPA, APs, and APEOs
in NIST Standard Reference Material (SRM) 2585 (Organic contaminants in house
dust) and in settled house dust samples. Results: Target analytes included BPA, 4
tert-octylphenol (OP), OP monoethoxylate, OP diethoxylate, 4-n-nonylphenol
(4nNP), 4nNP monoethoxylate (4nNP1EO), branched nonylphenol (NP), NP
monoethoxylate, NP diethoxylate, NP triethoxylate, and NP tetraethoxylate. The
method was sensitive, with method detection limits ranging from 0.05 to 5.1
MUg/g, and average recoveries between 82 and 115%. All target analytes were
detected in SRM 2585 and house dust except 4nNP and 4nNP1EO. Conclusions: The
method is simple and fast, with high sensitivity and good reproducibility. It is
applicable to the analysis of target analytes in similar matrixes, such as
sediments, soil, and biosolids. Highlights: Values measured in SRM 2585 will be
useful for future research in method development and method comparison.
PMID- 29945693
TI - A Validated Routine Method for Butyltin Determination in Seafood by Gas
Chromatography Inductively Coupled Plasma Isotope Dilution Mass Spectrometry.
AB - Organotin compounds are anthropogenic metal species with multiple uses as
pesticides, preservatives, antifouling agents, biocides, and catalysts. Butyltins
are the main organotin compounds found in biota, and the highest levels are found
in marine foodstuffs. In this paper, we present the figures of merit for an in
house validated method for routine analysis of butyltins in seafood using GC
inductively coupled plasma isotope dilution MS. The working range of the method
spanned several orders of magnitude from 3.3-1013, 2.4-785, and 0.3-900 ng Sn/g
dry weight for monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT),
respectively. The trueness of the method was evaluated by analyzing Certified
Reference Materials (CRMs) ERM CRM 477 (Mussel Tissue) and NIES CRM 15 (Scallop).
Recoveries, with RSD % in parentheses, were 78 (+/-14), 80 (+/-6), and 88% (+/
8%) for MBT, DBT, and TBT in ERM CRM 477 and 96% (+/-5%) for TBT in NIES CRM 15.
Good agreements were found between experimental uncertainties and uncertainties
predicted for single-laboratory validated methods calculated from the maximum
standard measurement uncertainty function. The method has proven to be robust,
and the wide range of seafood validated ensures that the method is applicable for
measuring butyltins in marine tissue.
PMID- 29945694
TI - Extraction Optimization for Phenolic- and Withanolide-Rich Fractions from
Withania somnifera Roots: Identification and Quantification of Withaferin A, 12
Deoxywithastromonolide, and Withanolide A in Plant Materials and Marketed
Formulations Using a Reversed-Phase HPLC-Photodiode Array Detection Method.
AB - Background: Both the roots and leaves of Withania somnifera are products of
commerce. They contain active compounds of therapeutic value and mostly different
withanolides. Several pharmacological activities of W. somnifera have links to
one or more withanolides. The presence of phenolic compounds in extracts could
play a vital role in the reduction of blood glucose levels in diabetic subjects.
Objective: The present study was carried out for the selection of a solvent to
prepare extracts rich in phenolics, withaferin A (WA), 12-deoxywithastromonolide
(12WD), and withanolide A (WDA). A simple, rapid HPLC method was also developed
for the identification and quantification of WA, 12WD, and WDA. Methods: The
extraction efficiency of aqueous alcoholic solvents including hexane, chloroform,
ethyl acetate, and methanol were compared for three selected withanolides and
total phenolic content. The contents of WA, 12WD, and WDA and total phenolics
were determined in the extracts. The quality of nine formulations containing W.
sominfera were also compared in terms of the content of WA, 12WD, and WDA and
total phenolics. Results: The maximum extract yield and the total withanolide and
phenolic content were obtained from aqueous alcoholic compositions at 50:50
(v/v), 70:30 (v/v), and 100:0 (v/v), respectively. In the case of organic
solvents, chloroform and ethyl acetate yielded the highest concentrations of
phenolics and three withanolides, respectively. The total phenolic content in
formulations was in the range of 1.84-3.13%, and total withanolide content showed
wide variability. Conclusions: The outcome of the present investigation could be
utilized for the selection of extraction solvents to prepare W. somnifera
enriched extracts and their quality monitoring by using the developed and
validated HPLC-Photodiode array detection method. Highlights: A process for
preparation of phenolics and withanolides (withaferin A, 12
deoxywithastramonolide and withanolide A) enriched extracts of Withania
somnifera. Simple and rapid HPLC method was also developed and validated as per
the ICH guidelines for identification and quantification of three major
withanolides. The developed HPLC method was applied to analyze the quality of
extracts and marketed herbal products (mono, as well as poly constituents).
Optimized extraction process could be utilized for upscaling process development
in preparation of enriched extracts from Withania somnifera, crop improvement,
bio-prospection studies and quality control.
PMID- 29945695
TI - Determination of Aflatoxins in Edible Oils from China and Ethiopia Using
Immunoaffinity Column and HPLC-MS/MS.
AB - Background: Aflatoxin (AF) ingestion through contaminated foodstuffs causes at
least 250000 deaths every year from hepatocellular carcinoma in China and sub
Saharan Africa. Objective: The main objective of the study was to determine the
aflatoxin levels of oils in South Gondar, Ethiopia, and oils purchased from
retail markets in Guangzhou, China. Methods: We used a rapid, sensitive, and
selective HPLC-tandem mass spectrometry (MS/MS) method for the determination of
aflatoxins in edible oils from China and Ethiopia using immunoaffinity column
cleaning. Results: The level of contamination for Ethiopian oils ranged between
0.07 and 145.59 MUg/kg for total aflatoxins. Of the 27 edible oil samples from
Guangzhou, China, the total concentration of aflatoxins (AFB1 + AFB2 + AFG1 +
AFG2) ranged between 0.03 and 2.23 MUg/kg. Conclusions: The study concluded that
the peanut oils from Ethiopia were contaminated with aflatoxins higher than the
allowable limit set by many countries while the oils from China were safe for
human consumption. Highlights: We first describe an HPLC-MS/MS method for the
determination of aflatoxins in 48 edible oil samples from China and Ethiopia
using immunoaffinity column cleaning. This is the first preliminary study done on
Ethiopian edible oils, giving policy-makers and future researchers baseline data.
It is also used to assess the aflatoxin levels of the Chinese edible oils from
Guangzhou. Therefore, conducting a comparative study points out the severity of
the problem and helps to formulate a new national standard for policy-makers,
making this study imperative.
PMID- 29945696
TI - The potential value of crowdsourced surveillance systems in supplementing
sentinel influenza networks: the case of France.
AB - IntroductionParticipatory surveillance systems provide rich crowdsourced data,
profiling individuals and their health status at a given time. We explored the
usefulness of data from GrippeNet.fr, a participatory surveillance system, to
estimate influenza-related illness incidence in France. Methods: GrippeNet.fr is
an online cohort since 2012 averaging ca. 5,000 weekly participants reporting
signs/symptoms suggestive of influenza. GrippeNet.fr has flexible criteria to
define influenza-related illness. Different case definitions based on reported
signs/symptoms and inclusions of criteria accounting for individuals' reporting
and participation were used to produce influenza-related illness incidence
estimates, which were compared to those from sentinel networks. We focused on the
2012/13 and 2013/14 seasons when two sentinel networks, monitoring influenza-like
illness (ILI) and acute respiratory infections (ARI) existed in France. Results:
GrippeNet.fr incidence estimates agreed well with official temporal trends, with
a higher accuracy for ARI than ILI. The influenza epidemic peak was often
anticipated by one week, despite irregular participation of individuals. The
European Centre for Disease Prevention and Control ILI definition, commonly used
by participatory surveillance in Europe, performed better in tracking ARI than
ILI when applied to GrippeNet.fr data. Conclusion: Evaluation of the epidemic
intensity from crowdsourced data requires epidemic and intensity threshold
estimations from several consecutive seasons. The study provides a standardised
analytical framework for crowdsourced surveillance showing high sensitivity in
detecting influenza-related changes in the population. It contributes to improve
the comparability of epidemics across seasons and with sentinel systems. In
France, GrippeNet.fr may supplement the ILI sentinel network after ARI
surveillance discontinuation in 2014.
PMID- 29945697
TI - Resurgence risk for measles, mumps and rubella in France in 2018 and 2020.
AB - BackgroundLarge measles and mumps outbreaks recently occurred throughout Europe
and the United States. Aim: Our aim was to estimate and map the risk of
resurgence for measles, mumps and rubella in France. Methods: We used a multi
cohort model combining seroprevalence information, vaccine coverage and social
contact data. Results: The overall outbreak risk for France in 2018 was highest
for mumps, remained significant for measles despite a recent measles outbreak and
was low for rubella. Outbreak risks were heterogeneous between departments, as
the effective reproduction numbers for 2018 ranged from 1.08 to 3.66. The
seroprevalence, and therefore the risk of measles and rubella infection, differed
significantly between males and females. There was a lower seroprevalence, and
therefore a higher risk, for males. Infants of less than 1 year would be
seriously affected in a future outbreak of measles, mumps or rubella, but the
highest overall caseload contribution would come from teenagers and young adults
(10-25 years old). Conclusions: The high risk for teenagers and young adults is
of concern in view of their vulnerability to more severe measles, mumps and
rubella disease and complications.
PMID- 29945698
TI - Uptake and impact of vaccinating primary school-age children against influenza:
experiences of a live attenuated influenza vaccine programme, England, 2015/16.
AB - The 2015/16 influenza season was the third season of the introduction of an intra
nasally administered live attenuated influenza vaccine (LAIV) for children in
England. All children aged 2-6 years were offered LAIV, and in addition, a series
of geographically discrete areas piloted vaccinating school-age children 7-11
years old. Influenza A(H1N1)pdm09 was the dominant circulating strain during
2015/16 followed by influenza B. We measured influenza vaccine uptake and the
overall and indirect effect of vaccinating children of primary school -age, by
comparing cumulative disease incidence in targeted and non-targeted age groups in
vaccine pilot and non-pilot areas in England. Uptake of 57.9% (range: 43.6-72.0)
was achieved in the five pilot areas for children aged 5-11 years. In pilot
areas, cumulative emergency department respiratory attendances, influenza
confirmed hospitalisations and intensive care unit admissions were consistently
lower, albeit mostly non-significantly, in targeted and non-targeted age groups
compared with non-pilot areas. Effect sizes were less for adults and more severe
endpoints. Vaccination of healthy primary school-age children with LAIV at
moderately high levels continues to be associated with population-level
reductions in influenza-related respiratory illness. Further work to evaluate the
population-level impact of the programme is required.
PMID- 29945699
TI - Reducing demand for antibiotic prescriptions: evidence from an online survey of
the general public on the interaction between preferences, beliefs and
information, United Kingdom, 2015.
AB - BACKGROUND: Antimicrobial resistance (AMR), a major public health threat, is
strongly associated with human antibiotic consumption. Influenza-like illnesses
(ILI) account for substantial inappropriate antibiotic use; patient understanding
and expectations probably play an important role. AIM: This study aimed to
investigate what drives patient expectations of antibiotics for ILI and
particularly whether AMR awareness, risk preferences (attitudes to taking risks
with health) or time preferences (the extent to which people prioritise good
health today over good health in the future) play a role. METHODS: In 2015, a
representative online panel survey of 2,064 adults in the United Kingdom was
asked about antibiotic use and effectiveness for ILI. Explanatory variables in
multivariable regression included AMR awareness, risk and time preferences and
covariates. RESULTS: The tendency not to prioritise immediate gain over later
reward was independently strongly associated with greater awareness that
antibiotics are inappropriate for ILI. Independently, believing antibiotics were
effective for ILI and low AMR awareness significantly predicted reported
antibiotic use. However, 272 (39%) of those with low AMR awareness said that the
AMR information we provided would lead them to ask a doctor for antibiotics more
often, significantly more than would do so less often, and in contrast to those
with high AMR awareness (p < 0.0001). CONCLUSION: Information campaigns to reduce
AMR may risk a paradoxical consequence of actually increasing public demand for
antibiotics. Public antibiotic stewardship campaigns should be tested on a small
scale before wider adoption.
PMID- 29945700
TI - [Expression of Acetaldehyde Dehydrogenase in Gefitinib-resistant Human Lung
Adenocarcinoma HCC-827/GR Cells].
AB - BACKGROUND: Tumor recurrence and drug resistance are the main causes of death in
tumor patients. The family of acetaldehyde dehydrogenase (ALDH) is closely
related to the proliferation, migration, invasion and resistance of tumor cells,
and different ALDH subtypes are expressed in different tumor cells. The aim of
this study is to elucidate the ALDH subtype in human lung adenocarcinoma HCC
827/GR cells, which resistant to the gefitinib. METHODS: The human lung
adenocarcinoma HCC-827 cells were used to generate the gefitinib-resistant HCC
827/GR cells; the expression of ALDH subtype in either HCC-827 or HCC-827/GR was
detected by flow cytometry; The proliferative capacity and sensitivity to
gefitinib of hcc-827/GR cells were analyzed by MTT assay before and after
treatment with 100 MUmol/L diethyllaminaldehyde (DEAB); Real-time quantitative
PCR was used to detect the expression of ALDH subtypes at mRNA levels in hcc-827
cells and hcc-827/GR cells. RESULTS: Compared with HCC-827 cells, the positive
rate of ALDH in HCC-827/GR cells increased. The proliferation ability of HCC
827/GR cells decreased after treatment with 100 MUmol/L DEAB. Compared with HCC
827 cells, the expression of ALDH1A1 and ALDH1L1 mRNA was increased in hcc-827/GR
cells, but the ALDH3B2 expression was decreased. CONCLUSIONS: ALDH might be used
as a molecular biomarker to test the gefitinib-resistant to lung adenocarcinoma
cancer cells, and the ALDH1A1 may play a role in gefitinib resistance in lung
cancer.
PMID- 29945701
TI - [Efficacy of S-1 in Advanced Non-small Cell Lung Cancer Patients Treated ?with
More Than Two Lines of Chemotherapy].
AB - BACKGROUND: There is no standard treatment for advanced non-small cell lung
cancer (NSCLC) after the failure of two lines of chemotherapy, S-1 as the third
generation of fluorouracil derivate with well safety and low toxicity, presented
some efficacy in lung cancer treatment. The aim of this study is to explore the
efficacy of S-1 for advanced NSCLC patients treated with two or more prior
chemotherapy regimens. METHODS: We performed a retrospective analysis of 105
NSCLC patients treated with S-1 monotherapy or S-1 contained chemotherapy as the
third or more line of treatment in our hospital from January 2014 to April 2017.
S-1 was administrated orally twice daily for 2 weeks, followed by one week of
rest, the dose of drug was determined by body surface area (<1.25 m2, 80 mg/d;
1.25 m2-1.5 m2, 100 mg/d; >=1.5 m2, 120 mg/d), platinum or the third-generation
chemotherapy drugs could be combinedly used. Clinical response was assigned every
cycle according to Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1, Kaplan-Meier analysis was used to estimate progression-free survival (PFS).
RESULTS: 42 patients received S-1 monotherapy, the other 63 patients received
combined regimens, the median treatment line was 4 (3-11) and the median
treatment cycle was 2 (1-14). No complete response (CR) were observed, there were
4 patients with partial response (PR), 34 patients with stable disease (SD) and
67 patients with progressive disease (PD), the objective response rate (ORR) was
3.81%, disease control rate (DCR) was 36.19%. The median PFS was 1.90 months
(0.67 months-10.83 months), no difference between monotherapy and combined group
(DCR: 28.56% vs 41.27%, P=0.185), the liver metastasis showed poorer PFS (1.40
months vs 1.93 months , P=0.042). CONCLUSIONS: S-1 presented some activity in
advanced NSCLC treated with more than two lines of treatment. The addition of
other drugs cannot improve efficacy. S-1 monotherapy can be used as a choice for
heavily-treated patients.
PMID- 29945702
TI - [Expression and Clinical Significance of LC-3 and P62 ?in Non-small Cell Lung
Cancer].
AB - BACKGROUND: LC-3 and P62, two of important autophagy-related proteins, were
reported highly expressed in many kinds of human malignancies and associated with
outcomes of the patients. The purpose of this study was to investigate the
expression status of LC-3 and P62 in non-small cell lung cancer patients and
define the clinical-pathologic features. METHODS: 66 cases of non-small cell lung
cancer patients were employed. The expression of LC-3 and P62 were detected by
immunohistochemistry. RESULTS: LC-3 was positive stained in 27 out of 66 cases
(40.9%) and P62 was positive stained in 43 out of 66 cases (65.2%). LC-3 positive
staining was more frequently in squamous cell carcinoma patients (P<0.05); while
P62 positive staining was more frequently in late-stage adenocarcinoma patients
with metastasis (P<0.05). There was a significant negative correlation between LC
3 and P62 expressions in non-small cell lung cancer tissues (rs=-0.065, P<0.001).
Kaplan-Meier analysis showed that patients with positive LC-3 expression had
favorable clinical outcomes compared with the patients with negative LC-3
expression (P<0.05). CONCLUSIONS: LC-3 and P62 showed abnormal expression in non
small cell lung cancer tissues, suggesting that autophagy is involved in the
occurrence and development of NSCLC.
PMID- 29945704
TI - [Severe Adverse Reactions Induced by the Chest Injection of Elemene: ?An Analysis
of 7 Cases].
AB - BACKGROUND: Malignant pleural effusion (MPE) refers to pleural effusion which
arises from primary malignant tumor of pleura or other pleural metastatic tumors.
Injection of elemene in chest makes good effect on the treatment of MPE, and is
widely used in clinic. Adverse effects also exist, but the severe adverse effects
and relevant managements are rarely reported. The aim of this study is to observe
the adverse reactions induced by the treatment of malignant pleural effusion
through elemene injection and to explore the solutions. METHODS: A retrospective
analysis was made on 14 cases of patients receiving intra-pleural injections with
elemene, and the incidence of severe adverse reactions of 7 cases were disscussed
in detail. RESULTS: Most of the severe adverse reactions caused by elemene were
severe chest pain, dyspnea, wheezing, clouding of consciousness and coagulopathy.
CONCLUSIONS: Strict screening, full preprocessing and close monitoring are
necessary to prevent serious adverse reactions caused by elemene injection in the
treatment of malignant pleural effusion.
PMID- 29945703
TI - [Value of CT Features on Differential Diagnosis of Pulmonary Subsolid Nodules and
Degree of invasion Prediction in Pulmonary Adenocarcinoma].
AB - BACKGROUND: Subsolid pulmonary nodules are common computed tomography (CT)
findings of primary lung adenocarcinoma. It is of clinical value to determine the
clinical treatment strategies based on CT features. The aim of this study is to
find the valuable CT characteristics on differential diagnosis and the degree of
invasion prediction by a retrospectively analysis of three groups subsolid
nodules, including benign, and invasive adenocarcinoma. METHODS: The CT findings
of 106 cases of resected sub-solid nodules were retrospectively analyzed. The
nodules were firstly divided into benign and malignant groups and the malignant
group was further divided into non/micro-invasive group (atypical adenomatous
hyperplasia/adenocarcinoma in situ/minimally invasive adenocarcinoma) and
invasive adenocarcinoma group. The nodule size, proportion of solid components,
tumor-lung interface, shape, margin, pleural traction, air bronchus sign,
vascular abnormalities inside the nodule were evaluated. The univariate analysis
(chi2 test, non-parametric test Mann-Whitney U test) was performed to screen
statistically significant variables and then enrolled in further multivariate
Logistic regression analysis. RESULTS: Multivariate logistic regression analysis
showed that a clear tumor-lung interface, air bronchus sign, and pulmonary
vascular abnormalities were important indicators of malignant nodules with hazard
ratios of 38.1 (95%CI: 5.0-287.7; P<0.01), 7.9 (95%CI: 1.3-49.3; P=0.03), 7.2
(95%CI: 1.4-37.0; P=0.02), respectively. The proportion of solid components was
the only significant indicator for identifying invasive adenocarcinoma from
AAH/AIS/MIA , with a risk ratio of 1.04 (95%CI: 1.01-1.06, P=0.01). CONCLUSIONS:
SSNs with clear tumor-lung interface, air bronchus sign, and pulmonary vascular
abnormality inside nodule are more likely to be malignant. A higher percentage of
solid components indicates a higher likelihood to be an invasive lesion in
malignant SPNs.
PMID- 29945705
TI - [Risk Factors of Nodal Upstaging in Clinical Ia Lung Adenocarcinoma].
AB - BACKGROUND: In clinical Ia (cT1N0M0) patients, some may have poor prognosis, for
it might occur pathologic N1 (pN1) or N2 (pN2) postoperatively. The aim of this
study is to determine the radiologicaland pathological factors related to
clinical Ia adenocarcinoma. METHODS: The retrospective study was conducted on 297
clinical Ia adenocarcinoma patients resected at our hospital between May 2012 to
December 2016. The clinical profiles, radiological and pathological features were
analyzed between nodal upstaging group and non-upstaging group. RESULTS: Of 297
patients treated for cN0 tumors, 250 cases (84.2%) were confirmed postoperatively
as having pN0 tumors, and 47 (15.8%) were confirmed as having pN1 or pN2 tumors.
Female, low smoking index, micropapillary predominant and solid predominant
adenocarcinoma, puresolid tumor and large tumor size were all more frequently
seen in the nodal upstaging group than in the pN0 group (P<0.05). Logistic
regression indicate that radiological solid tumor, micropapillary predominant and
solid predominant adenocarcinoma and vessel invasionare the risk factors of nodal
upstaging in clinical Ia adenocarcinoma. CONCLUSIONS: Radiological solid tumors,
micropapillary predominant and solid predominant adenocarcinoma andvessel
invasion are risk factors for nodal upstaging for early stage lung cancer.
Radiological solid tumors should perform SLND in Ia adenocarcinomas.
PMID- 29945706
TI - [Bioinformatics Analysis of DNA Methylation in the Promoters of LincRNA ?in Lung
Adenocarcinoma].
AB - BACKGROUND: Previous studies have found the lincRNAs play important roles in the
occurrence and development of lung adenocarcinoma, but their regulated mechanims
are still unclear. The aim of this study is to evaluate the relationship between
DNA methylation and lincRNA expression, and the effect of prognosis in lung
adenocarcinoma. METHODS: The whole genome Illumina Methylation 450 DNA
methylatiuon data and RNAseq for lung adenocarcinoma were download from TCGA. DNA
methylation around lincRNA and their relationship to gene expression were
analyzed. Their contribution to lung adenocarcinoma were further analyzed by
comparing DNA methylation and lincRNA expression in tumor and adjacent tissues.
RESULTS: The methylation level in promoter region was lower than other positions
in lincRNA, and was negatively correlated with gene expression. There were 427
lincRNA genes showed differential DNA methylation in their promoter regions in
tumor and adjacent tissues. Among these, 15 lincRNA genes showed differential
gene expression and negatively correlated with DNA methylation, including FENDRR
(a tumor progression and metastasis gene) whose high methylation in its promoter
showed poor survival in lung adenocarcinoma. CONCLUSIONS: The expression of
lincRNA can be regulated by DNA methylation in their promoter regions, and the
level of DNA methylation is related to patient prognosis in lung adenocarcinoma.
PMID- 29945707
TI - [Risk Factors of Non-small Cell Lung Cancer with Bone Metastasis after Therapy].
AB - BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, patients
with non-small cell lung cancer (NSCLC) usually have distant metastases, such as
bone metastasis, brain metastasis, and lung metastasis. The purpose of this study
was to explore the risk factors for bone metastasis in NSCLC patients. METHODS: A
total of 176 cases of NSCLC were selected from May 2009 to May 2011, and patients
were divided into two groups, namely the bone metastasis group and non-bone
metastasis group. The general clinicopathological data of the two groups and
analyzing the independent risk factors of bone metastasis were compared. RESULTS:
In the general clinicopathological data of NSCLC patients. The thrombus or not
and tumor-node-metastasis (TNM) stage were closely related to the occurrence of
bone metastasis, and were statistically significant (all P<0.01). Prothrombin
time, activated partial thromboplastin time, Fibrinogen, thrombin time, blood
platelet, D-Dimer and alkaline phosphatase have significantly difference between
the two groups (all P<0.05). Logistic regression analysis showed that fibrinogen,
activated partial thromboplast in time, alkaline phosphatase, T4 phase, N3 phase
and d-dimer were independent risk factors for bone metastasis in NSCLC patients.
CONCLUSIONS: Fibrinogen, alkaline phosphatase, T3, N2 stage and D-Dimer is the
independent risk factors of bone metastases in patients with NSCLC.?.
PMID- 29945709
TI - [Advance of Treatment for Superior Sulcus Tumor of the Lung].
AB - Superior sulcus tumor of the lung is a bronchogenic tumor occurred in the apex of
the upper lobe of the lung and is a unique clinical subtype of non-small cell
lung cancer (NSCLC), which account for less than 5% of all bronchogenic
carcinomas. It often involves the first rib, brachial plexus, subclavian vessels,
sympathetic chain, stellate ganglion or vertebra. A lot of progress has been
achieved in the treatment of superior sulcus tumor over the past decades. Several
clinical trials reported in recent years have confirmed that concurrent
chemoradiotherapy followed by surgical resection can improve the rate of complete
resection, local control and pathological remission of the tumor, and prolong the
total-survival time. It has become the most effective treatment mode for the
superior sulcus tumor, and recommended as a standard treatment mode for superior
sulcus tumor by National Comprehensive Cancer Network (NCCN) and American College
of Chest Physicians (ACCP) guidelines. This article reviews relevant literatures
at home and abroad, and briefly introduces the advances in surgical treatment and
comprehensive treatment of superior sulcus tumor.?.
PMID- 29945708
TI - [Impact of the Pretreatment or Posttreatment NLR and PLR on the Response of First
Line Chemotherapy and the Outcomes in Patients with Advanced Non-small Cell Lung
Cancer].
AB - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio
(PLR), indexes of systemic inflammation, have been associated with worse survival
for many types of cancer. The aim of this study is to investigate the impact of
NLR and PLR on overall survival (OS) and to explore the value of changes in the
NLR and PLR with treatment as a response indicator in non-small cell lung cancer
(NSCLC). METHODS: A total of 68 NSCLC patients in Peking University Third
Hospital were eligible for retrospective analysis between April 2008 and April
2015. The pretreatment and posttreatment NLR and PLR in all patients were
calculated based on complete blood counts. Potential prognostic factors such as
age, gender, performance status, histology, stage, response to chemotherapy, NLR
and PLR were analyzed. NLR and PLR were assessed at baseline and during
chemotherapy treatment. OS was calculated by the Kaplan-Meier method. Univariate
and multivariate Cox regression analyses were performed to determine the
associations of the PLR, NLR and clinical features with OS. RESULTS: Among the 68
cases, the values of the posttreatment NLR after two cycles of chemotherapy
(NLR2) and the pretreatment NLR (NLR0) were (2.69+/-2.06) and (3.94+/-2.12),
respectively. NLR2 was significantly lower than NLR0 (P=0.000). There was no
difference between the pretreatment PLR (PLR0) and the posttreatment PLR after
two cycles of chemotherapy (PLR2) (P<0.05). NLR2 significantly correlated with
the response of first line treatment with two or four cycles of chemotherapy. The
proportion of high NLR2 in the patients with progression disease was 100.0%,
significantly higher than the proportion of high NLR2 in the patients with
partial response or stable disease. NLR0, PLR0 and NLR2 were significantly
correlated with the OS (P<0.05), but not with age, performance status, histology,
stage, status and regimens of treatment (P>0.05). According to univariate
analysis, the OS was significantly associated with NLR0, PLR0, NLR2, the response
of 2 and 4 cycles of first line chemotherapy, status and regimens of second line
treatment (P<0.05), but not with stage, status of third line or beyond treatment
and radiotherapy (P>0.05). The multivariate analysis showed that NLR0 (P=0.004),
the response with 4 cycles of first line chemotherapy (P=0.022) and status of
second line treatment (P=0.007) were independent prognostic indicators in the 68
patients. CONCLUSIONS: The study showed that NLR0 was well connected with
outcomes and NLR2 was well connected with the response to first line chemotherapy
in patients with advanced non-small cell lung cancer. Therefore, NLR may be a
biomarker for predicting the outcomes and response of first line chemotherapy and
a potential target for management of non-small cell lung cancer.
PMID- 29945710
TI - [Progress of Lung Margin During Sublobar Resection for Early-staged Non-small
Cell Lung Cancer].
AB - In recent years, with the popularization of low-dose computed tomography (LDCT)
and high-resolution CT (HRCT), the discovery rate of early-staged non-small cell
lung cancer has been on the rise, and more thoracic surgeons have explored more
reasonable resection scope. Clinical studies have demonstrated that there is a
lower rate of local tumor recurrence in patients with negative lung margins
compared with positive ones. Therefore, it is of great clinical significance to
ensure the negative margin during sublobar resection for early-staged lung
cancer. This paper will focus on this area.?.
PMID- 29945712
TI - [Is it worth delivering Direct-Current Counter shock to critically ill patients
with supra-ventricular tachyarrhythmia?]
AB - : Supra-ventricular tachyarrhythmia and its treatment have been poorly
investigated in ICU patients. AIMS: To evaluate efficacy and safety of
cardioversion for supra-ventricular tachyarrhythmia in the intensive care unit
(ICU). PATIENTS AND METHODS: Prospective inclusion of all patients who presented
supra-ventricular tachyarrhythmias lasting>=30seconds in a single medico-surgical
ICU, except cardiac surgery. Anti-arrhythmic drugs and/or direct-current
cardioversion were administered on a liberal basis. RESULTS: During the 15-month
study period, 108/846 patients (12.8%) experienced supra-ventricular
tachyarrhythmias. Anti-arrhythmic drugs were administered in 78 patients (72%);
mostly amiodarone (92%), and/or magnesium (23%), resulting in an overall
conversion rate of 68%. Direct-current cardioversion was used in 26 patients
(24%), (24 patients received drug enhancement by anti-arrhythmic drugs) with an
immediate 80.8%-success rate. CONCLUSION: Direct-current cardioversion was
associated with sustained conversion to sinus rhythm in 80.8% of ICU patients
with supra-ventricular tachyarrhythmias, although most of them had already
received drug enhancement.
PMID- 29945711
TI - Does progesterone prophylaxis to prevent preterm labour improve outcome? A
randomised double-blind placebo-controlled trial (OPPTIMUM).
AB - BACKGROUND: Progesterone prophylaxis is widely used to prevent preterm birth but
is not licensed and there is little information on long-term outcome. OBJECTIVE:
To determine the effect of progesterone prophylaxis in women at high risk of
preterm birth on obstetric, neonatal and childhood outcomes. DESIGN: Double
blind, randomised placebo-controlled trial. SETTING: Obstetric units in the UK
and Europe between February 2009 and April 2013. PARTICIPANTS: Women with a
singleton pregnancy who are at high risk of preterm birth because of either a
positive fibronectin test or a negative fibronectin test, and either previous
spontaneous birth at <= 34 weeks+0 of gestation or a cervical length of <= 25 mm.
INTERVENTIONS: Fibronectin test at 18+0 to 23+0 weeks of pregnancy to determine
risk of preterm birth. Eligible women were allocated (using a web-based
randomisation portal) to 200 mg of progesterone or placebo, taken vaginally daily
from 22+0 to 24+0 until 34+0 weeks' gestation. Participants, caregivers and those
assessing the outcomes were blinded to group assignment until data collection was
complete. MAIN OUTCOME MEASURES: There were three primary outcomes, as follows:
(1) obstetric - fetal death or delivery before 34+0 weeks' gestation; (2)
neonatal - a composite of death, brain injury on ultrasound scan (according to
specific criteria in the protocol) and bronchopulmonary dysplasia; and (3)
childhood - the Bayley-III cognitive composite score at 22-26 months of age.
RESULTS: In total, 96 out of 600 (16%) women in the progesterone group and 108
out of 597 (18%) women in the placebo group had the primary obstetric outcome
[odds ratio (OR) 0.86, 95% confidence interval (CI) 0.61 to 1.22]. Thirty-nine
out of 589 (7%) babies of women in the progesterone group and 60 out of 587 (10%)
babies of women in the placebo group experienced the primary neonatal outcome [OR
0.62, 95% CI 0.38 to 1.03]. The mean Bayley-III cognitive composite score of the
children at 2 years of age was 97.3 points [standard deviation (SD) 17.9 points;
n = 430] in the progesterone group and 97.7 points (SD 17.5 points; n = 439) in
the placebo group (difference in means -0.48, 95% CI -2.77 to 1.81). LIMITATIONS:
Overall compliance with the intervention was 69%. HARMS: There were no major
harms, although there was a trend of more deaths from trial entry to 2 years in
the progesterone group (20/600) than in the placebo group (16/598) (OR 1.26, 95%
CI 0.65 to 2.42). CONCLUSIONS: In this study, progesterone had no significant
beneficial or harmful effects on the primary obstetric, neonatal or childhood
outcomes.The OPPTIMUM trial is now complete. We intend to participate in a
comprehensive individual patient-level data meta-analysis examining women with a
singleton pregnancy with a variety of risk factors for preterm birth. TRIAL
REGISTRATION: Current Controlled Trials ISRCTN14568373. FUNDING: This trial was
funded by the Medical Research Council (MRC) and managed by the National
Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.
PMID- 29945713
TI - Dental treatment of a rare case of pyoderma gangrenosum with aggressive
periodontal disease.
AB - BACKGROUND AND OVERVIEW: Pyoderma gangrenosum (PG) is a rare neutrophil-mediated
autoinflammatory dermatosis that can involve the oral mucosa. Dental surgery is a
potential triggering factor for the onset of PG lesions. The authors describe and
discuss the dental management of a rare case of aggressive periodontitis in a
patient with PG, from multiple tooth extractions to prosthetic rehabilitation,
including administration of systemic steroid prophylaxis before surgery to
prevent the potential onset of PG-related lesions. CASE DESCRIPTION: A 22-year
old man who had a diagnosis of PG and who had aggressive periodontal disease
underwent dental extractions, gingivoplastic surgery, and prosthetic
rehabilitation. The patient received 8 milligrams of betamethasone
intramuscularly 20 minutes before the oral surgery. The tissues healed perfectly,
and no adverse effects were reported. CONCLUSIONS AND PRACTICAL IMPLICATIONS: For
minor oral surgery, prophylactic corticosteroids might help reduce the risk of
developing PG-related lesions. The clinician should plan the prosthetic devices
to be as atraumatic as possible.
PMID- 29945714
TI - Stability of sufentanil and baclofen mixtures for intrathecal analgesia at
different concentrations in polypropylene syringes.
AB - BACKGROUND: Intrathecal analgesia is a method using various molecules alone or in
combination. Among these, the association sufentanil/ baclofen is widely used.
Instead of moving patients to the few expert centers taking charge of these
specific preparations, it could be better to transport syringes to peripheral
centers managing pump refilling. That is why, it is interesting to demonstrate
the stability of the mixture, and so to be able to ensure the best transport
conditions of syringes. METHODS: A stability indicating UPLC-DAD method was
developed and validated according to the ICH guidelines. Four mixtures of
sufentanil baclofen stored in 5+/-3 degrees C and 25+/-2 degrees C were evaluated
for seven days and compared to the initial observed concentrations. RESULTS: The
stability is demonstrated only for preparations stored at 5+/-3 degrees C for
seven days thanks to relative concentrations (95% confidence intervals of the
mean of 3 samples) systematically positioned between 90% and 110%. On the other
hand, after few days, degradation products of sufentanil appeared for all
mixtures stored at 25 degrees C+/-2 degrees C. CONCLUSION: This study shows the
stability of a weakly and a highly concentrated mixture of sufentanil and
baclofen solutions in polypropylene syringes stored at 5+/-3 degrees C for seven
days. This result will allow the transport of the preparation under optimal
conditions. Advance preparations for intrathecal pump refills could also be
feasible.
PMID- 29945715
TI - [Retrocession, a profitable but risky activity].
AB - : The retrocession (out-patient dispensing of hospital-reserved drugs)is a
pharmaceutical critical activity requiring a care security with a territorial
approach. In this drug supply chain, the pharmacist is the last step before the
drug administration and the economic profitability is questionable. In this
context, a risk mapping and an economic evaluation seem necessary. METHODS: The
risk analysis was conducted with the adverse events collected. The economic study
was realised with the point of view of the hospital and with the microcosting
method. RESULTS: Six never events were observed with the risk analysis. The
economic study showed that the retrocession was profitable in usual situations
with a net margin from 7 to 14?. But, when an exceptional situation occurred as a
troubleshooting or the creation of a public deal, the added costs became so
important (76 and 85?) that the retrocession was an unbeneficial activity.
CONCLUSION: The retrocession is an activity with a health, legal and economic
high risk. In order to improve the healthcare quality and safety, the
retrocession must be considered as a coordinated process. It means that the
different health professionals must communicate with each other and that the
connection between the ambulatory and the hospital care must be efficient.
PMID- 29945717
TI - Cataract risk of neuro-interventional procedures: a nationwide population-based
matched-cohort study.
AB - AIM: To demonstrate the risk of cataract associated with radiation exposure from
neuro-interventional procedures. MATERIALS AND METHODS: This was a nationwide
population-based, matched-cohort study. The exposed group (group E) comprised
patients diagnosed with an aneurysm, cerebrovascular system anomaly, or
subarachnoid haemorrhage who underwent a neuro-interventional procedure, such as
brain digital subtraction angiography or endovascular embolisation. The
comparison group (group C) included subjects who were never exposed to radiation
from neuro-interventional procedures and were propensity score-matched by the
date of enrolment, age, sex, and associated comorbidities. Multiple Cox
proportional hazard regression analysis was used to estimate the hazard ratio
(HR) of cataract risk due to radiation exposure while adjusting for potential
confounding factors. RESULTS: There were 838 patients and 3,352 matched subjects
in groups E and C, respectively. The incidence of cataracts was significantly
greater among subjects in group E (adjusted HR [aHR] = 1.88; 95% confidence
interval [CI] = 1.08-3.26), especially those aged >40 years (aHR = 2.14; 95% CI =
1.16-3.94). The number of computed tomography examinations was positively
correlated, but not statistically significant, with an increased risk of cataract
occurrence. CONCLUSIONS: Neuro-interventional procedures might be significantly
associated with an increased risk of cataract occurrence.
PMID- 29945718
TI - AMPA Receptor Activation-Independent Antidepressant Actions of Ketamine
Metabolite (S)-Norketamine.
AB - BACKGROUND: Ketamine, an N-methyl-D-aspartate receptor antagonist, exerts robust
antidepressant effects in patients with treatment-resistant depression. The
precise mechanisms underlying ketamine's antidepressant actions remain unclear,
although previous research suggests that alpha-amino-3-hydroxy-5-methyl-4
isoxazole propionic acid receptor (AMPAR) activation plays a role. We
investigated whether (S)-norketamine and (R)-norketamine, the two main
metabolites of (R,S)-ketamine, also play a significant role in ketamine's
antidepressant effects and whether the effects are mediated by AMPAR. METHODS:
Cellular mechanisms of antidepressant action of norketamine enantiomers were
examined in mice. RESULTS: (S)-Norketamine had more potent antidepressant effects
than (R)-norketamine in inflammation and chronic social defeat stress models.
Furthermore, (S)-norketamine induced more beneficial effects on decreased
dendritic spine density and synaptogenesis in the prefrontal cortex and
hippocampus compared with (R)-norketamine. Unexpectedly, AMPAR antagonists did
not block the antidepressant effects of (S)-norketamine. The electrophysiological
data showed that, although (S)-norketamine inhibited N-methyl-D-aspartate
receptor-mediated synaptic currents, (S)-norketamine did not enhance AMPAR
mediated neurotransmission in hippocampal neurons. Furthermore, (S)-norketamine
improved reductions in brain-derived neurotrophic factor-tropomyosin receptor
kinase B signaling in the prefrontal cortex of mice susceptible to chronic social
defeat stress, whereas the tropomyosin receptor kinase B antagonist and a
mechanistic target of rapamycin inhibitor blocked the antidepressant effects of
(S)-norketamine. In contrast to (S)-ketamine, (S)-norketamine did not cause
behavioral abnormalities, such as prepulse inhibition deficits, reward effects,
loss of parvalbumin immunoreactivity in the medial prefrontal cortex, or baseline
gamma-band oscillation increase. CONCLUSIONS: Our data identified a novel AMPAR
activation-independent mechanism underlying the antidepressant effects of (S)
norketamine. (S)-Norketamine and its prodrugs could be novel antidepressants
without the detrimental side effects of (S)-ketamine.
PMID- 29945719
TI - Consequences of Pharmacological BACE Inhibition on Synaptic Structure and
Function.
AB - Alzheimer's disease is the most prevalent neurodegenerative disorder among
elderly persons. Overt accumulation and aggregation of the amyloid-beta peptide
(Abeta) is thought to be the initial causative factor for Alzheimer's disease.
Abeta is produced by sequential proteolytic cleavage of the amyloid precursor
protein. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the
initial and rate-limiting protease for the generation of Abeta. Therefore,
inhibiting BACE1 is considered one of the most promising therapeutic approaches
for potential treatment of Alzheimer's disease. Currently, several drugs blocking
this enzyme (BACE inhibitors) are being evaluated in clinical trials. However,
high-dosage BACE-inhibitor treatment interferes with structural and functional
synaptic plasticity in mice. These adverse side effects may mask the therapeutic
benefit of lowering the Abeta concentration. In this review, we focus on the
consequences of BACE inhibition-mediated synaptic deficits and the potential
clinical implications.
PMID- 29945721
TI - Mitochondrial DNA Transcription and Its Regulation: An Evolutionary Perspective.
AB - The bacterial heritage of mitochondria, as well as its independent genome
[mitochondrial DNA (mtDNA)] and polycistronic transcripts, led to the view that
mitochondrial transcriptional regulation relies on an evolutionarily conserved,
prokaryotic-like system that is separated from the rest of the cell. Indeed,
mtDNA transcription was previously thought to be governed by a few dedicated
direct regulators, namely, the mitochondrial RNA polymerase (POLRMT), two
transcription factors (TFAM and TF2BM), one transcription elongation (TEFM), and
one known transcription termination factor (mTERF1). Recent findings have,
however, revealed that known nuclear gene expression regulators are also involved
in mtDNA transcription and have identified novel transcriptional features
consistent with adaptation of the mitochondria to the regulatory environment of
the precursor of the eukaryotic cell. Finally, whereas mammals follow the human
mtDNA transcription pattern, other organisms notably diverge in terms of mtDNA
transcriptional regulation. Hence, mtDNA transcriptional regulation is likely
more evolutionary diverse than once thought.
PMID- 29945720
TI - A global Unified Dosimetry Index (gUDI) to evaluate simultaneous integrated boost
radiotherapy plans in prostate cancer.
AB - PURPOSE: Formulation of a global Unified Dosimetry Index (gUDI) for the
evaluation of prostate simultaneous integrated boost Volumetric Modulated Arc
Therapy (VMAT by RapidArc) radiotherapy plans. METHODS AND MATERIALS: Dose
coverage, conformity, homogeneity and dose gradient index could be included in
the Unified Dosimetry Index (UDI). We developed a global UDI to evaluate
treatment plans containing volumes irradiated with different dose prescriptions:
Intensity Modulated Radiation Therapy with simultaneous integrated boost (IMRT
SIB) with 2 dose levels (36.25 Gy/5 fz for the whole prostate gland and 37.5 Gy/5
fz for Dominant Intraprostatic Lesion (DIL)). To validate gUDI scoring system, 65
prostate cancer patients were evaluated. Mean (u) and standard deviations (sigma)
were calculated for all dosimetry indices and gUDI. Furthermore, gUDI u and sigma
were analyzed to compare and classify treatment plans: plans can be ranked as
"excellent", "good", "average" or "poor". RESULTS: Prostate Dose Gradient,
Prostate Conformity and DIL Conformity indices had highlighted a major deviation
from ideal scores. gUDI index classification showed most of the plans scored as
"average" and "good". CONCLUSION: gUDI score can be a useful tool to quantify
treatment plans quality also when volumes with different dose-prescription are
treated.
PMID- 29945722
TI - Navigating the highlights of EAS Congress Lisbon.
PMID- 29945723
TI - Reply to: "Strokes, cholesterol and statins: When mortality is an endpoint".
PMID- 29945724
TI - Reply to the letter "Airway management in intensive care units".
PMID- 29945725
TI - The Increasingly Human and Profitable Monoclonal Antibody Market.
AB - The monoclonal antibody (mAb) market has changed rapidly in the past 5 years: it
has doubled in size, becoming dominated by fully human molecules, launched
bispecific molecules, and faced competition from biosimilars. We summarize the
market in terms of therapeutic applications, type and structure of mAbs, dominant
companies, manufacturing locations, and emerging markets.
PMID- 29945726
TI - The Berg Balance Scale as a clinical screening tool to predict fall risk in older
adults: a systematic review.
AB - BACKGROUND: The Berg Balance Scale (BBS) is often used in clinical practice to
predict falls in the older adults. However, there is no consensus in research
regarding its ability to predict falls. OBJECTIVE: To verify whether the BBS can
predict falls risk in older adults. DATA SOURCE: Manual and electronic searches
(Medline, EMBASE, CINAHL, Ageline, Lilacs, Web of Science, Cochrane Library and
PEDro) were conducted using blocks of words (older adults, falls, BBS, study
design) and their synonyms, with no language restrictions and published since
1989. STUDY SELECTION CRITERIA: Prognostic studies or clinical trials were used
to assess the BBS and falls history. DATA EXTRACTION AND DATA SYNTHESIS: In this
narrative synthesis, two independent assessors extracted data from articles and a
third reviewer provided consensus, in case of disagreement. The methodological
quality was assessed using the Quality In Prognosis Studies tool. RESULTS: 1047
studies were found and 8 studies were included in this review. The mean BBS score
was high, regardless of the history of falls. Three studies presented cut-off
scores for BBS, ranging from 45 to 51 points. Two studies reported a difference
in the BBS score between fallers and non-fallers. Studies presented low to
moderate risk of bias. LIMITATIONS: Unfeasible to conduct a meta-analysis due the
heterogeneity of included studies. CONCLUSION: The evidence to support the use of
BBS to predict falls is insufficient, and should not be used alone to determine
the risk of falling in older adults. SYSTEMATIC REVIEW REGISTRATION NUMBER:
PROSPERO CRD42016032309.
PMID- 29945727
TI - MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight
patients with type 2 diabetes: a randomised, controlled, double-blind, ascending
dose and phase 2a study.
AB - BACKGROUND: Weight loss is often key in the management of obese or overweight
patients with type 2 diabetes, yet few treatments for diabetes achieve clinically
meaningful weight loss. We aimed to assess the efficacy, tolerability, and safety
of treatment with MEDI0382, a balanced glucagon-like peptide-1 and glucagon
receptor dual agonist developed to provide glycaemic control and weight loss, in
patients with type 2 diabetes. METHODS: This randomised, placebo-controlled,
double-blind, combined multiple-ascending dose (MAD) and phase 2a study was done
at 11 study sites (hospitals and contract research organisations) in Germany. We
enrolled patients aged 18-65 years with controlled type 2 diabetes (glycated
haemoglobin A1c [HbA1c] levels of 6.5-8.5% at screening) and a body-mass index
between 27 kg/m2 and 40 kg/m2. An interactive web-response system was used to
randomly assign patients to receive MEDI0382 or placebo. Patients were randomly
assigned 2:1 in cohorts A-C and 3:1 in cohorts D and E in the MAD portion of the
study, and 1:1 in the phase 2a portion. Randomisation was done by a contracted
third-party operator who was not involved in the clinical operations of the
study. The pharmacists, participants, and study site personnel involved in
treating and assessing participants were masked to treatment allocation. Patients
received once-daily subcutaneous injections of the study drug at doses of no more
than 300 MUg for 22 days or less in the MAD portion of the study, and a dose of
no more than 200 MUg for 41 days or less in the phase 2a portion. The two primary
endpoints of the phase 2a portion were the change from baseline to day 41 in
glucose area under the curve at 0-4 h (AUC0-4 h) after a mixed-meal tolerance
test (MMTT), assessed in all participants who received at least one dose of study
drug and whose measurements were taken at baseline and day 41, and change from
baseline in bodyweight, assessed in the intention-to-treat (ITT) population.
Safety analyses were done in all participants who received any study drug
analysed according to the treatment they received. This study is registered with
ClinicalTrials.gov, number NCT02548585. FINDINGS: Patients were recruited between
Dec 9, 2015, and Feb 24, 2017. 61 patients were randomly assigned to the MAD part
of the study (42 to MEDI0382 and 19 to placebo). 51 patients were randomly
assigned to the phase 2a part, of whom 25 were randomly assigned to MEDI0382 and
26 to placebo. In the phase 2a study, three patients in the MEDI0382 group and
one in the placebo group discontinued, all as a result of adverse events. 22
(88%) patients in the MEDI0382 group and 25 (96%) in the placebo group received
at least one dose and had measurements taken at baseline and day 41. Glucose AUC0
4 h post MMTT decreased significantly with MEDI0382 versus placebo (least squares
[LS] mean -32.78% [90% CI -36.98 to -28.57] vs -10.16% [-14.10 to -6.21], and the
mean difference was -22.62% [-28.40 to -16.85]; p<0.0001). In the ITT population,
reduction in bodyweight was significantly greater with MEDI0382 than with placebo
(LS mean -3.84 kg [90% CI -4.55 to -3.12] vs -1.70 kg [-2.40 to -1.01] and mean
difference of 2.14 kg [-3.13 to -1.31]; p=0.0008). The proportion of patients who
had a treatment-emergent adverse event (TEAE) was similar between treatment
groups (22 [88%] of 25 in the MEDI0382 group vs 23 [88%] of 26 in the placebo
group); gastrointestinal disorders (18 [72%] vs 13 [40%]) and decreased appetite
(five [20%] vs none) occurred more frequently with MEDI0382 than placebo. No
participants in the MEDI0382 group had a grade 3 or worse TEAE (vs two [8%] in
the placebo group). INTERPRETATION: MEDI0382 has the potential to deliver
clinically meaningful reductions in blood glucose and bodyweight in obese or
overweight individuals with type 2 diabetes. FUNDING: MedImmune.
PMID- 29945728
TI - Agonism of receptors in the gut-pancreas axis in type 2 diabetes: are two better
than one?
PMID- 29945730
TI - Response to: New immunoassays for anti-HMG-CoA reductase antibodies may lead to
incorrect diagnosis in inflammatory myositis.
PMID- 29945729
TI - Analysis of the QuantiFERON-CMV assay, CMV viraemia and antiviral treatment
following solid organ transplantation in Western Australia.
AB - Prevention of cytomegalovirus (CMV) infection remains an important aspect of
improving long term outcomes of solid organ transplantation and currently relies
on prophylactic antiviral medication and early detection of viraemia or disease.
Uptake of diagnostic tools to personalise assessment of CMV immunity and guide
interpretation of viral testing remains low. We assessed the QuantiFERON-CMV
assay in 54 Western Australian recipients of renal, heart, lung or liver
allografts to determine the relationship between CMV-specific immunity, viraemia
and disease following cessation of antiviral prophylaxis. We carried out an
initial validation study which demonstrated that the QuantiFERON-CMV assay is
highly precise and strongly correlated with CMV-specific antibodies in 30 healthy
blood donors (sensitivity 82%, specificity 95%). In the solid organ transplant
recipients we examined, the prevalence of asymptomatic CMV viraemia was high at
61% but only two patients ultimately developed CMV disease, both of whom had
negative QuantiFERON-CMV responses, indicating lack of CMV T-cell immunity. The
vast majority (94%) of patients who had spontaneous resolution or stability of
asymptomatic CMV viraemia without any antiviral treatment had positive
QuantiFERON-CMV responses. Positive QuantiFERON-CMV responses at cessation of
antiviral prophylaxis were significantly associated with pre-transplant CMV
seropositivity and the development of asymptomatic viraemia post-transplantation.
Overall, 27% of patients were recommenced on antiviral therapy because of
asymptomatic CMV viraemia. Patients with non-reactive QuantiFERON-CMV responses
had earlier onset, higher level CMV viraemia compared to those with positive
QuantiFERON-CMV responses, although the difference did not reach statistical
significance. QuantiFERON-CMV results may contribute to decision making in
concert with the serological risk profile, net state of immunosuppression and CMV
viral load.
PMID- 29945731
TI - Effect of marine protected areas on distinct fish life-history stages.
AB - The role of Marine Protected Areas on distinct life stages of Mediterranean reef
fish species (classified on the basis of their economic value and mobility
categories) was assessed in a network of marine reserves in SE Spain. Only
abundance and biomass of adult of both commercial and demersal species were
positively affected by protection. Gradients across reserve boundaries (as a clue
to the occurrence of spillover) were observed for fish abundance but not for
biomass, indicating a protected fish assemblage with a predominance of small
sized individuals. Also, post-larvae of commercial species were negatively
related to protected zones. Active selection of settlement preferred habitats,
larval accumulation favoured by the geomorphological configuration of the coast
or mixed effects has been proposed as possible explanations. Juveniles showed
high spatial variability resulting in a lack of response to fishing protection
measures. We highlight the need of including early life stages and overall
suitable habitats for them when designing MPA networks due to the crucial
importance of these stages to successful fulfillment of MPA objectives.
PMID- 29945732
TI - The Importance of Economic Trade-offs in Cancer Drug Pricing.
PMID- 29945733
TI - Letter to the editor regarding "Generalized anxiety disorder in urban China:
Prevalence, awareness, and disease Burden" [J. Affect. Disord. 234 (2018) 89-96].
PMID- 29945734
TI - ER Proteostasis Control of Neuronal Physiology and Synaptic Function.
AB - Neuronal proteostasis is maintained by the dynamic integration of different
processes that regulate the synthesis, folding, quality control, and localization
of proteins. The endoplasmic reticulum (ER) serves as a fundamental pillar of the
proteostasis network, and is emerging as a key compartment to sustain normal
brain function. The unfolded protein response (UPR), the main mechanism that
copes with ER stress, plays a central role in the quality control of many ion
channels and receptors, in addition to crosstalk with signaling pathways that
regulate connectivity, synapse formation, and neuronal plasticity. We provide
here an overview of recent advances in the involvement of the UPR in maintaining
neuronal proteostasis, and discuss its emerging role in brain development,
neuronal physiology, and behavior, as well as the implications for
neurodegenerative diseases involving cognitive decline.
PMID- 29945735
TI - The effects of recruitment maneuver during noninvasive ventilation after coronary
bypass grafting: A randomized trial.
AB - OBJECTIVE: Pulmonary impairment is a common complication after coronary artery
bypass graft procedure and may be prevented or treated by noninvasive
ventilation. Recruitment maneuvers include sustained airway pressure with high
levels of positive end-expiratory pressure in patients with hypoxemia, favoring
homogeneous pulmonary ventilation and oxygenation. This study aimed to evaluate
whether noninvasive ventilation with recruitment maneuver could safely improve
oxygenation in patients with atelectasis and hypoxemia who underwent a coronary
artery bypass grafting procedure. METHODS: Thirty-four patients admitted to our
intensive care unit undergoing mechanical ventilation after surgery, with ratio
of arterial oxygen partial pressure to fraction of inspired oxygen < 300 and
radiologic atelectasis score >=2, were included. The control group consisted of
16 randomized patients and the recruitment group consisted of 18 patients. After
extubation, noninvasive ventilation was applied for 30 minutes 3 times a day with
positive end-expiratory pressure of 8 cm H2O. The recruitment group received
recruitment maneuver with positive end-expiratory pressure of 15 cm H2O and 20 cm
H2O for 2 minutes each during noninvasive ventilation. We analyzed the arterial
oxygen partial pressure in room air, radiologic atelectasis score, hemodynamic
stability, and adverse events from extubation until discharge. RESULTS: Arterial
oxygen partial pressure increased 12.6% +/- 6.8% in the control group and 23.3%
+/- 8.5% in the recruitment group (P < .001). The radiologic atelectasis score
was completely improved for 94.4% of the recruitment group with no adverse
events, whereas 87.5% of the control group presented some atelectasis (P < .001).
CONCLUSIONS: Noninvasive ventilation with recruitment maneuvers is safe, improves
oxygenation, and reduces atelectasis in patients undergoing coronary artery
bypass.
PMID- 29945736
TI - Another step toward successful mechanical support of neonatal patients with
single-ventricle circulation.
PMID- 29945737
TI - Participation of membrane calcium channels in erythropoietin-induced endothelial
cell migration.
AB - Calcium (Ca2+) plays an important role in angiogenesis, as it activates the cell
migration machinery. Different proangiogenic factors have been demonstrated to
induce transient Ca2+ increases in endothelial cells. This has raised interest in
the contribution of Ca2+ channels to cell migration, and in a possible use of
channel-blocking compounds in angiogenesis-related pathologies. We have
investigated the ability of erythropoietin (Epo), a cytokine recently involved in
angiogenesis, to induce Ca2+ influx through different types of membrane channels
in EA.hy926 endothelial cells. The voltage-dependent Ca2+ channel antagonists
amlodipine and diltiazem inhibited an Epo-triggered transient rise in
intracellular Ca2+, similarly to a specific inhibitor (Pyr3) and a blocking
antibody against the transient potential calcium channel 3 (TRPC3). Unlike
diltiazem, amlodipine and the TRPC3 inhibitors prevented the stimulating action
of Epo in cell migration and in vitro angiogenesis assays. Amlodipine was also
able to inhibit an increase in endothelial cell migration induced by Epo in an
inflammatory environment generated with TNF-alpha. These results support the
participation of Ca2+ entry through voltage-dependent and transient potential
channels in Epo-driven endothelial cell migration, highlighting the
antiangiogenic activity of amlodipine.
PMID- 29945739
TI - Childhood emotional abuse characteristics moderate associations with adult
psychopathology and caregiving.
AB - As the consequences of childhood maltreatment for adult adjustment become
increasingly established in the literature, investigations of individual
differences in these effects must evolve to examine more nuanced components of
the maltreatment experience. This is particularly true for studies of childhood
emotional abuse (CEA), which represents an umbrella label for numerous
qualitatively different experiences. The present study examined the distinct
contributions and potential interactive effects of CEA frequency and intensity on
adult psychopathology, caregiving behaviors, and caregivers' representations of
the caregiver-child relationship in a diverse sample of 62 female caregivers of 4
year-old children, all of whom had experienced CEA. Frequency and intensity
emerged as orthogonal characteristics of CEA with differential effects on adult
adaptation. Higher CEA frequency predicted increased adult psychopathology,
whereas higher CEA intensity predicted increased boundary dissolution in
caregivers' representations. Further, an interaction between frequency and
intensity predicted negativity in caregivers' representations, such that higher
frequency of high intensity, but not low intensity, CEA predicted decreased
negativity. Neither frequency nor intensity of CEA predicted observed caregiving
behaviors. These results provide evidence that characteristics of CEA signal
important differences in its experience, with differential implications for later
adjustment. The specific differences in caregiving representations associated
with high vs. low intensity CEA suggest that diverging mechanisms by which these
experiences eventuate in adult outcomes should also be investigated. Above all,
this study suggests that the measurement of CEA, and childhood maltreatment
broadly, will benefit from enhanced attention to specific characteristics of
individuals' experiences.
PMID- 29945738
TI - A Randomized, Multicenter, Double-blind, Phase III Study to Evaluate the Efficacy
on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and
Levocetirizine in Patients With Asthma and Allergic Rhinitis.
AB - PURPOSE: The aim of this study was to evaluate the efficacy and safety of a fixed
dose combination of montelukast and levocetirizine in patients with perennial
allergic rhinitis with mild to moderate asthma compared with the efficacy and
safety of montelukast alone. METHODS: This study was a 4-week, randomized,
multicenter, double-blind, Phase III trial. After a 1-week placebo run-in period,
the subjects were randomized to receive montelukast (10 mg/day, n = 112) or
montelukast (10 mg/day)/levocetirizine (5 mg/day) (n = 116) treatment for 4
weeks. The primary efficacy end point was mean daytime nasal symptom score. Other
efficacy end points included mean nighttime nasal symptom score, mean composite
symptom score, overall assessment of allergic rhinitis by both subjects and
physicians, forced expiratory volume in 1 second (FEV1), forced vital capacity
(FVC), FEV1/FVC, asthma control test score, and the frequency of rescue
medication used during the treatment period. FINDINGS: Of 333 patients screened
for this study, 228 eligible patients were randomized to treatment. The mean (SD)
age of patients was 43.32 (15.02) years, and two thirds of subjects were female
(66.67%). The demographic characteristics were similar between the treatment
groups. Compared with the montelukast group, the montelukast/levocetirizine group
reported significant reductions in mean daytime nasal symptom score (least
squares mean [SE] of combination vs montelukast, -0.98 [0.06] vs -0.81 [0.06]; P
= 0.045). For all other allergic rhinitis efficacy end points, the
montelukast/levocetirizine group showed greater improvement than the montelukast
group. Similar results were observed in overall assessment scores and in FEV1,
FVC, FEV1/FVC, and asthma control test score changes from baseline for the 2
treatment groups. Montelukast/levocetirizine was well tolerated, and the safety
profile was similar to that observed in the montelukast group. IMPLICATIONS: The
fixed-dose combination of montelukast and levocetirizine was effective and safe
in treating perennial allergic rhinitis in patients with asthma compared with
montelukast alone. ClinicalTrials.gov identifier: NCT02552667.
PMID- 29945740
TI - A longitudinal human phantom reliability study of multi-center T1-weighted, DTI,
and resting state fMRI data.
AB - Multi-center MRI studies can enhance power, generalizability, and discovery for
clinical neuroimaging research in brain disorders. Here, we sought to establish
the utility of a clustering algorithm as an alternative to more traditional intra
class correlation coefficient approaches in a longitudinal multi-center human
phantom study. We completed annual reliability scans on 'travelling human
phantoms'. Acquisitions across sites were harmonized prospectively. Twenty-seven
MRI sessions were available across four participants, scanned on five scanners,
across three years. For each scan, three metrics were extracted: cortical
thickness (CT), white matter fractional anisotropy (FA), and resting state
functional connectivity (FC). For each metric, hierarchical clustering (Ward's
method) was performed. The cluster solutions were compared to participant and
scanner using the adjusted Rand index (ARI). For all metrics, data clustered by
participant rather than by scanner (ARI > 0.8 comparing clusters to participants,
ARI < 0.2 comparing clusters to scanners). These results demonstrate that
hierarchical clustering can reliably identify structural and functional scans
from different participants imaged on different scanners across time. With
increasing interest in data-driven approaches in psychiatric and neurologic brain
imaging studies, our findings provide a framework for multi-center analytic
approaches aiming to identify subgroups of participants based on brain structure
or function.
PMID- 29945741
TI - Estrogen, progesterone, and the menstrual cycle: A systematic review of fear
learning, intrusive memories, and PTSD.
AB - Women are disproportionately affected by posttraumatic stress disorder (PTSD),
and gonadal hormones are implicated in fear learning processes associated with
PTSD. In rodents, lower estradiol, particularly during metestrus when
progesterone is also low, is associated with impaired extinction. Based on
theories that extinction deficits underlie PTSD, individuals with lower estradiol
and progesterone may exhibit fear learning deficits and higher PTSD
symptomatology. A systematic review was conducted in PsycInfo, PubMed, and
Medline databases for studies examining estradiol, progesterone, or menstrual
phase in relation to fear learning or PTSD symptoms. Twenty-three studies are
organized into fear learning (k = 17) and PTSD symptom (k = 12) studies. Across
fear learning studies, higher estradiol was consistently associated with enhanced
fear extinction recall and inconsistently and weakly associated with better
extinction learning and fear acquisition, respectively. Extending to PTSD
symptoms, the association with hormonal status was reversed, such that luteal
phase, associated with higher estradiol and progesterone, was generally
associated with higher re-experiencing symptoms. Overall, human fear learning
studies were consistent with rodent studies. Despite strong experimental links
between fear learning processes and PTSD, the clinical translation was
inconsistent and may reflect varying methods, imprecise measurement, and greater
complexity of hormonal effects on symptomatology.
PMID- 29945743
TI - Total Skin Electron Irradiation and Sequential Malignancies in Mycosis Fungoides
Patients: Longitudinal Study.
AB - AIMS: To determine the role of total skin electron irradiation (TSEI) as a cause
of second malignancies in mycosis fungoides patients. MATERIALS AND METHODS:
Mycosis fungoides patients referred to TSEI were followed in a longitudinal
study. Other diagnosed malignancies were obtained after cross-matching with the
Israel National Cancer Registry database. RESULTS: Between 1974 and 2010, 197
patients were treated: 134 (68%) men, 63 (32%) women; mean age 58 +/- 17years.
Topical/systemic treatment was given to 134 (68%) patients. TSEI was given to 104
(68.9%) patients. Seven (4.6%) received sub-TSEI and 40 (26.5%) received focal
electron irradiation fields. Forty-six (23%) patients did not receive
radiotherapy. The second primaries rate was 6.7 times higher in male mycosis
fungoides patients and 13.1 times higher in female mycosis fungoides patients
than in the general Israeli population. Malignant melanoma developed in eight
patients after radiotherapy, in one patient without irradiation. The skin-related
cancer rate after irradiation versus no irradiation was higher (P = 0.018).
Combination radiotherapy with psoralen + ultraviolet A and/or nitrogen mustard
yielded 11 cases of skin cancer versus no cases without irradiation. CONCLUSIONS:
Mycosis fungoides patients have a high incidence of sequential malignancies. TSEI
is associated with higher 'skin-related cancer' rates. Close longitudinal follow
up of mycosis fungoides patients is obligatory.
PMID- 29945742
TI - On-treatment lipid profiles to predict the cardiovascular outcomes in ASCVD
patients comorbid with chronic kidney disease - The multi-center T-SPARCLE
registry study.
AB - BACKGROUND: The aim of this study is to determine the relationship between the on
treatment lipid profiles and the CV events in CKD and non-CKD population. METHOD:
This study was a multi-center observational registry, the Taiwanese Secondary
Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. This
study follows up patients with CV diseases in Taiwan who have secondary
prevention therapies. The primary outcome is the time of first occurrence of a
major adverse cardiac events (MACEs). RESULT: 5388 patients with ASCVD were
included and 1478 (27.4%) had CKD without dialysis. CKD patients had higher TG
and lower LDL-C levels. The incidence of recurrent MACEs per 1000 person-years in
CKD patients was 19.5 (95% CI 15.5-24.9), compared with 9.1 (95% CI 7.4-11.1) in
non-CKD patients. In patients with statin therapy, there were no differences in
MACE risk between each level of on-treatment LDL-C, TG and HDL-C level. Higher on
treatment non-HDL-C level was a significant predictor for higher MACE risk in
patients without CKD, and borderline significant in CKD patients under statin
therapy. Heart failure history was also associated with higher MACE risk in both
group. Lower body mass index (BMI < 23 kg/m2) was associated with higher MACE
risk in CKD patients. CONCLUSION: In ASCVD patients, on-treatment LDL-C was not a
good CV outcome predictor. Instead, on-treatment non-HDL-C was a better
predictor. Heart failure history was also associated with higher MACE risk in
both group of patients. Lower BMI (<23 kg/m2) was associated with higher
recurrent MACE risk in CKD patients.
PMID- 29945744
TI - Current scenario of plasmid-mediated colistin resistance in Latin America.
AB - Colistin resistance can occur by chromosomal mutations and by acquisition of
plasmid-carrying determinants, mainly mcr-1. In the recent years, we have
observed the outburst of this resistance gene in our region. Due to the risk of
the rapid dissemination of mcr-1, this finding has worried and alerted different
actors from the health field and has become one of the most prolific topics. Our
review compiles available reports of well-documented mcr-1-positive strains of
Enterobacteriaceae, obtained from different samples in Argentina and other
countries of Latin America. Furthermore, it addresses the association of mcr-1
with ESBL resistance markers and outlines the platforms involved in their
dissemination.
PMID- 29945746
TI - Opportunities and perspectives for utilisation of co-products in the meat
industry.
AB - Meat co-products are the non-meat components arising from meat
processing/fabrication and are generated in large quantities on a daily basis. Co
products are considered as low added-value products, and in general it is
difficult for industries to divert efforts into increasing their value. While
many of these products can be edible those not used for human consumption or pet
food is usually processed to be used as animal feed, fertilizer or fuel. However,
to a large extent meat co-products are an excellent source of high nutritive
value protein, minerals and vitamins and hence may be better diverted to
contribute to alleviate the increasing global demand for protein. In this review
the current uses, legislation and potential techniques for meat co-products
processing are reviewed with the aim of showing a route to improve meat industry
sustainability, profitability and better usage of available resources.
PMID- 29945745
TI - A brief history of meat in the human diet and current health implications.
AB - Anthropological investigations have confirmed many times over, through multiple
fields of research the critical role of consumption of animal source foods (ASF)
including meat in the evolution of our species. As early as four million years
ago, our early bipedal hominin ancestors were scavenging ASFs as evidenced by cut
marks on animal bone remains, stable isotope composition of these hominin remains
and numerous other lines of evidence from physiological and paleo-anthropological
domains. This ASF intake marked a transition from a largely forest dwelling
frugivorous lifestyle to a more open rangeland existence and resulted in numerous
adaptations, including a rapidly increasing brain size and altered gut structure.
Details of the various fields of anthropological evidence are discussed, followed
by a summary of the health implications of meat consumption in the modern world,
including issues around saturated fat and omega-3 fatty acid intake and
discussion of the critical nutrients ASFs supply, with particular emphasis on
brain function.
PMID- 29945747
TI - Effects of residual speech and auditory deprivation on speech perception of adult
cochlear implant recipients.
AB - OBJECTIVE: Possible predictive factors of cochlear implant (CI) outcomes have
been extensively reported in literature for different user groups such as
prelingual pediatric or postlingual adult users. However, there remains
unexplained outcome variability among adult CI users; therefore, research
concerning these patients continues and many different variables have been
reported. This study aimed at evaluating the relationship between preoperative
speech reception capacity, residual hearing, duration of deafness, age of
implantation, and postoperative monosyllabic word recognition scores (WRSs) in
postlingual CI users. METHODS: Effect of onset age of hearing loss, duration of
hearing loss, cochlear implantation age, pre CI speech reception thresholds (SRT)
and pre CI WRS on the post-CI WRS of 76 adults were analyzed. RESULTS: There are
statistically significant relationships between hearing loss duration, pre-CI
WRS, residual hearing and the post CI WRS. We observed that patients with shorter
auditory deprivation with measurable speech perceptions and residual hearing
might perform better with CI. CONCLUSION: Ear selection in cases of unilateral CI
should be considered on an individual basis with respect to the speech perception
abilities.
PMID- 29945748
TI - Cerebellar infarction following accidental inhalation of toluene-mixed paint.
AB - We report a case of atypical cerebellar infarction following accidental
inhalation of toluene mixed paint. An unconscious 57-year-old housewife with
hypertension arrived at our emergency department by ambulance. She had been
rescued from a basement (30 m3) 12 h after exposure to paint containing toluene
(34%). On arrival, she was comatose (E1V1M1) with a mild fever (37.4 degrees C).
Physical examination showed chemical burns on her buttocks and rales on the left
lung. Initial arterial blood gas with 15 L/min of oxygen showed a pH of 7.142,
PCO2 of 47.3 mmHg, and PaO2 of 204.7 mmHg. She received endotracheal intubation
and mechanical ventilation. Laboratory tests showed elevated white blood cells
(26.86 * 109/L), C-reactive protein (0.18 mg/dL), glucose (238 mg/Dl), and CPK
(1389 U/L). At 5.5 h after arrival, she became responsive to verbal commands. On
day 3, after removal of the endotracheal tube, she began to complain of an
occipital headache without neurologic abnormalities. Brain magnetic resonance
angiography (MRA) performed on day 6 showed a tiny acute infarction on the right
cerebellar hemisphere. We serially measured urinary hippuric acid concentrations
(reference range, <=2.5 g/g creatinine) from 74 h (3.88) after hospital arrival
to 218 h (0.5). She was discharged on day 14. Herein we presented a near fatal
toluene intoxication (>45,000 mg/m3 estimated based on the basement volume and
quantity of paint used) with atypical cerebellar infarction, compared with prior
findings of bilateral involvement or reversibility.
PMID- 29945749
TI - Immediate births or not so immediate births - comparing like with like.
PMID- 29945751
TI - Inflammatory Breast Cancer: Updates on diagnosis and treatment options.
PMID- 29945750
TI - Response letter to correspondence.
PMID- 29945752
TI - Translational Opportunities and Challenges of Long Noncoding RNAs in Cardiac
Regeneration.
PMID- 29945753
TI - ROS1-Rearranged Non-Small-Cell Lung Cancer, Factor V Leiden, and Recurrent Venous
Thromboses.
PMID- 29945754
TI - Malone antegrade continence enema: Is cecal imbrication essential?
AB - INTRODUCTION: The Malone antegrade continence enema (MACE) procedure is effective
in management of fecal incontinence and intractable constipation. Stomal
incontinence and stenosis are the most common issues reported, and a recent large
study of imbricated MACE procedures reports a surgical revision rate of 17%. The
laparoscopic approach is now widely used and precludes imbrication. To date, few
studies have reported revision rates in these patients who have undergone non
imbricated MACE creation. OBJECTIVE: Our goal was to report the long-term
outcomes of our non-imbricated patients focusing on complication rates and need
for revision. STUDY DESIGN: Records of patients younger than 18 years of age who
underwent non-imbricated MACE between January 2000 and March 2016 at our
institution were reviewed. Patients with less than 2 years of follow-up or non
compliance with MACE usage were excluded from analysis. Patient age, ambulatory
status, surgical technique, stomal site, and complications including stomal
leakage, stomal stenosis, and need for revision were evaluated. Stomal leakage
was classified based on our previously reported system. RESULTS: A total of 81
patients met inclusion criteria. Mean age at time of surgery was 8.4 years. Mean
and median follow-up were 6.7 and 6.7 years, respectively. Overall revision rate,
for stenosis or incontinence, was 16% with a mean time to any revision of 2.1
years (range 28 days to 7.8 years). Four patients required revision for stomal
incontinence while others improved spontaneously without intervention. At the
last follow-up, stomal leakage was grade 0 in 93.8% of patients, grade 2 in 2.4%,
and grade 3a in 3.7% (summary Table). Stomal stenosis was noted in 11 patients,
eight of whom required revision. DISCUSSION: Our study is limited by its
retrospective nature with some component of recall bias. A single surgeon
experience is also not representative of others' experiences. However, our
results indicate that incontinence improves spontaneously in a majority of
patients without need for revision in this non-imbricated cohort. CONCLUSIONS:
Our series shows a similar long-term revision rate in line with that reported in
the literature. While imbrication is still recommended during open surgery when
the anatomy is suitable, equitable success without imbrication supports the
laparoscopic approach and a more liberal approach during open surgery if the
anatomy does not permit imbrication.
PMID- 29945756
TI - Design and synthesis of alkyl substituted pyridino[2,3-D]pyrimidine compounds as
PI3Kalpha/mTOR dual inhibitors with improved pharmacokinetic properties and
potent in vivo antitumor activity.
AB - Using pyridino[2,3-D]pyrimidine as the core, total 13 pyridino[2,3-D]pyrimidine
derivatives with different alkyl substituents at C2 site have been designed and
synthesized to search for novel PI3Kalpha/mTOR dual inhibitors. Most of the
target compounds showed potent mTOR inhibition activity with IC50 values ranging
from single to double digit nanomole. Five target compounds exhibited pronounced
PI3Kalpha inhibition activity. In vitro cellular assay indicated that most of the
target compounds showed excellent antiproliferative activity, especially 3j whose
potency against SKOV3 was 8-fold higher than the positive control AZD8055. In
vitro metabolic stability study found that 3j had a comparable stability to that
of AZD8055. More importantly, 3j showed better antitumor activity and
pharmacokinetic properties in vivo as compared with AZD8055.
PMID- 29945755
TI - Early small bowel obstruction after laparoscopic gastric bypass: a surgical
emergency.
AB - BACKGROUND: Early small bowel obstruction (ESBO; within 30 d of surgery) after
laparoscopic gastric bypass (LRYGB) is reported in .5% to 5.2% of primary cases,
but it is associated with significant morbidity, and the treatment is not
standardized. OBJECTIVES: To review prevalence, causes, management, and outcomes
of patients treated for ESBO after LRYGB. SETTING: Tertiary academic medical
center. METHODS: Retrospective review to identify consecutive patients who
underwent primary LRYGB and those who developed ESBO from January 2000 through
June 2017. Data included demographic characteristics, co-morbidities, LRYGB
technical details, and ESBO clinical presentation, location, causes, treatment,
and outcomes. RESULTS: One thousand seven hundred seventeen patients (84.2%
females) had LRYGB. Mean age and body mass index was 42.4 +/- 11.1 years and 48.2
+/- 7.3 kg/m2, respectively. Twenty-nine patients (1.7%) had ESBO. All patients
presented with symptoms, most commonly nausea and vomiting (n = 17), on average
4.1 +/- 5.9 days postoperatively; most required reoperation (n = 23, 79.3%) and 5
required >1 reoperation. Location of the obstruction and treatment used were the
following: (1) jejuno-jejunostomy (n = 17, 58.6%; narrowing or clot), treated
with reoperation in 11; and (2) other than at the jejuno-jejunostomy (n = 12,
41.4%; trocar site, incisional or internal hernia, adhesions, mesenteric
ischemia), treated with reoperation in all. All ESBO patients had additional
complications, 6 (20.1%) developed an anastomotic leak, and 2 (6.9%) died.
CONCLUSION: ESBO infrequently occurs after LRYGB; many causes are technique
related and possibly preventable. However, it is associated with significant
morbidity and mortality. A high index of clinical suspicion, rapid and
appropriate imaging, and prompt operative intervention are recommended.
PMID- 29945757
TI - Design, synthesis and pharmacology of aortic-selective acyl-CoA: Cholesterol O
acyltransferase (ACAT/SOAT) inhibitors.
AB - We describe our molecular design of aortic-selective acyl-coenzyme A:cholesterol
O-acyltransferase (ACAT, also abbreviated as SOAT) inhibitors, their structure
activity relationships (SARs) and their pharmacokinetic (PK) and pharmacological
profiles. The connection of two weak ligands-N-(2,6-diisopropylphenyl)acetamide
(50% inhibitory concentration [IC50] = 8.6 MUM) and 2-(methylthio)benzo[d]oxazole
(IC50 = 31 MUM)-via a linker comprising a 6 methylene group chains yielded a
highly potent molecule, 9-(benzo[d]oxazol-2-ylthio)-N-(2,6
diisopropylphenyl)nonanamide (3h) that exhibited high potency (IC50 = 0.004 MUM)
toward aortic ACAT. This head-to-tail design made it possible to markedly enhance
the activity to 2150- to 7750-fold and to discriminate the isoform-selectivity
based on the double-induced fit mechanism. At doses of 1 and 3 mg/kg, 3h
significantly decreased the lipid-accumulation areas in the aortic arch to 74 and
69%, respectively without reducing the plasma total cholesterol level in high fat
and cholesterol-fed F1B hamsters. Here, we demonstrate the antiatherosclerotic
effect of 3hin vivo via its direct action on aortic ACAT and its powerful
modulator of cholesterol level. This molecule is a potential therapeutic agent
for the treatment of diseases involving ACAT-1 overexpression.
PMID- 29945758
TI - iPSC-Derived Enterocyte-like Cells for Drug Absorption and Metabolism Studies.
AB - Intestinal cell models have been widely studied and used to evaluate absorption
and metabolism of drugs in the small intestine, constituting valuable tools as a
first approach to evaluate the behavior of new drugs. However, such cell models
might not be able to fully predict the absorption mechanisms and metabolic
pathways of the tested compounds. In recent years, induced pluripotent stem cells
(iPSCs) differentiated into enterocyte-like cells have been proposed as more
biorelevant intestinal models. In this review, we describe mechanisms underlying
the differentiation of iPSCs into enterocyte-like cells, appraise the usefulness
of these cells in tridimensional intestinal models, and discuss their suitability
to be used in the future for drug screening.
PMID- 29945759
TI - Premature Rejection of Plasticity in Conversion.
PMID- 29945760
TI - Nurses' Knowledge of Tuberculosis, HIV, and Integrated HIV/TB Care Policies in
Rural Western Cape, South Africa.
AB - HIV and tuberculosis (TB) co-infection remain the leading causes of mortality in
many developing countries. Several policies for their prevention and management
exist; however, progress to meet the World Health Organization's indicators is
slow. As nurses in rural areas are the main health care professionals responsible
for the implementation of policies, questions arose about nursing knowledge
regarding TB and HIV policies. A concurrent mixed method research approach was
used to investigate this issue in a rural area of the Western Cape in South
Africa. After a two-step sampling process, data were collected through 44
questionnaires and 12 interviews. We used descriptive and inferential statistics
as well as content analysis methods. We found that most of the nurses had
insufficient knowledge on certain aspects of policy guidelines that included
medications, intensive case findings, and management of multidrug-resistant TB.
It is recommended that training be intensified to improve implementation of
policies.
PMID- 29945761
TI - In silico dynamic characterization of the femur: Physiological versus mechanical
boundary conditions.
AB - It is established that bone tissue adapts and responds to mechanical loading.
Several studies have suggested an existence of positive influence of vibration on
the bone mass maintenance. Thus, some bone regeneration therapies are based on
vibration of bone tissue under circumstances of disease to stimulate its
formation. Frequency of loading should be properly selected and therefore a
correct characterization of the dynamic properties of this tissue may be critical
for the success of such orthopedic techniques. On the other hand, many studies
implement vibration techniques with in silico models. Numerical results are
exclusively dependent on properties of bone tissue, i.e. geometry, density
distribution and stiffness, as well as boundary conditions. In the present study,
the influence of boundary conditions and material properties on the dynamic
characteristics of bone tissue was explored in a human femur. Bone shape and
density were directly reconstructed from computer tomographies, whereas natural
frequencies and modes of vibration were obtained for different boundary
conditions including physiological and mechanical ones. Results of this study
show the moderate effect of material properties compared to the much substantial
effect of boundary conditions. A factor of 2 in the natural frequency was
obtained depending on imposed boundary conditions, highlighting the importance in
the selection of appropriate conditions in the analysis of the bone organ.
PMID- 29945762
TI - A novel stability-based EMG-assisted optimization method for the spine.
AB - Traditional electromyography-assisted optimization (TEMG) models are commonly
employed to compute trunk muscle forces and spinal loads for the design of
clinical/treatment and ergonomics/prevention programs. These models calculate
muscle forces solely based on moment equilibrium requirements at spinal joints.
Due to simplifications/assumptions in the measurement/processing of surface EMG
activities and in the presumed muscle EMG-force relationship, these models fail
to satisfy stability requirements. Hence, the present study aimed to develop a
novel stability-based EMG-assisted optimization (SEMG) method applied to a
musculoskeletal spine model in which trunk muscle forces were estimated by
enforcing equilibrium conditions constrained to stability requirements. That is,
second-order partial derivatives of the potential energy of the musculoskeletal
model with respect to its generalized coordinates were enforced to be positive
semi-definite. Fifteen static tasks in upright and flexed postures with and
without a hand load at different heights were simulated. The SEMG model predicted
different muscle recruitments/forces (generally larger global and local muscle
forces) and spinal loads (slightly larger) compared to the TEMG model. Such task
specific differences were dependant on the assumed magnitude of the muscle
stiffness coefficient in the SEMG model. The SEMG model-predicted and measured L4
L5 intradiscal pressures were in satisfactory agreement during simulated
activities.
PMID- 29945763
TI - Effectiveness of quadrivalent influenza vaccine based on the test-negative
control study in children during the 2016-2017 season.
AB - To estimate the vaccine effectiveness (VE) of quadrivalent influenza vaccine, I
conducted a test-negative case control study in children, based on the rapid
influenza diagnostic test (RIDT), during the 2016-2017 season. Overall, the
adjusted VE was significant for any influenza (influenza A + B); VE: 30.2% (95%
confidence interval [CI]: 5.4-48.4) and influenza B: 48.2% (95% CI: 11.3-69.7).
The participants were divided into three age groups (group A: 0-4 years old,
group B: 5-9 years old, and group C: 10-15 years old); in group A, the adjusted
VE of quadrivalent influenza vaccine was significant for any influenza (A + B):
58.6% (95% CI: 28.8-76.0), influenza A: 53.9% (95% CI: 16.4-74.6), and influenza
B: 78.6% (95% CI: 23.6-94.0). In both groups B and C, VE was not observed for any
of the types of influenza. In only group A, two doses of vaccines provided
significantly better VE against any influenza, as well as both influenzas A and
B, than single-dose vaccines and cases in which vaccination was not administered.
In conclusion, quadrivalent influenza vaccine showed significant VE and dose
dependent VE against any influenza and both influenzas A and B, in children aged
0-4 years during the 2016-2017 season. Both the VE and dose-dependent VE were
almost not observed in older group. However, this may due to low rate of
vaccination, particularly in children aged 10-15 years.
PMID- 29945764
TI - Can MRI-only replace MRI-CT planning with a titanium tandem and ovoid applicator?
AB - PURPOSE/OBJECTIVE(S): To evaluate dosimetric differences between MRI-only and MRI
CT planning with a titanium tandem and ovoid applicator to determine if all
imaging and planning goals can be achieved with MRI only. MATERIALS/METHODS: We
evaluated 10 patients who underwent MRI-CT-based cervical brachytherapy with a
titanium tandem and ovoid applicator. High-risk clinical target volume and organs
at risk were contoured on the 3D T2 MRI, which were transferred to the co
registered CT, where the applicator was identified. Retrospectively, three
planners independently delineated the applicator on the axial 3D T2 MRI while
blinded to the CT. Identical dwell position times in the delivered plan were
loaded. Dose-volume histogram parameters were compared to the previously
delivered MRI-CT plan. RESULTS: There were no significant differences in dose to
D90 or D98 of the high-risk clinical target volume with MRI vs. MRI-CT planning.
MRI vs. MRI-CT planning resulted in mean D0.1cc bladder of 8.8 +/- 3.4 Gy vs. 8.5
+/- 3.2 Gy (p = 0.29) and D2cc bladder of 6.2 +/- 1.4 Gy vs. 6.0 +/- 1.4 Gy (p =
0.33), respectively. Mean D0.1cc rectum was 5.7 +/- 1.2 Gy vs. 5.3 +/- 1.2 Gy (p
= 0.03) and D2cc rectum 4.0 +/- 0.8 Gy vs. 4.2 +/- 1.0 Gy (p = 0.18),
respectively. Mean D0.1cc sigmoid was 5.2 +/- 1.3 Gy vs. 5.4 +/- 1.6 Gy (p =
0.23) and D2cc sigmoid 3.9 +/- 1.0 Gy vs. 4.0 +/- 1.1 Gy (p = 0.18),
respectively. CONCLUSION: There were no clinically significant dosimetric
differences between the MRI and MRI-CT plans. This study demonstrates that
cervical brachytherapy with a titanium applicator can be planned with MRI alone,
which is now our clinical standard.
PMID- 29945765
TI - Modification of an engineered Escherichia coli by a combined strategy of deleting
branch pathway, fine-tuning xylose isomerase expression, and substituting
decarboxylase to improve 1,2,4-butanetriol production.
AB - 1,2,4-Butanetriol (BT) is an important precursor of energetic material 1,2,4
butanetriol trinitrate (BTTN) in military field. Here, the recombinant
Escherichia coli was modified by multi-strategy to increase BT production. First,
the 2-keto acid reduction pathway was blocked by double deleting the genes yiaE
and ycdW, resulting in 19% and 41% increase of BT titer and yield, respectively.
Further disruption of xylose branch pathway by deleting xylA gene led to a 24%
increase of BT yield, but the biomass and BT titer were decreased by 63% and 55%,
respectively. To balance the carbon flux for cell growth and BT biosynthesis, the
expression of xylA gene was interfered by antisense RNA. The biomass and BT
titers of all the mutants harboring asRNA were restored and the highest BT
production was improved by 214 %. Finally, substitute expression of the high
efficient decarboxylase KivD led to a 72% increase of BT titer (10.03 g/L), which
is significantly higher than previously reported (5.1 g/L). This work provided
some effective strategies for improving BT production by balancing the carbon
flux redistribution and reducing power regeneration.
PMID- 29945766
TI - Secondary Stroke Prophylaxis with Clopidogrel Produces Sufficient Antiplatelet
Response.
AB - BACKGROUND: Antiplatelet therapy is a cornerstone prevention strategy for
secondary ischemic stroke (IS) and transient ischemic attack (TIA). Yet, a
proportion of patients who receive antiplatelet therapy experience recurrent
ischemic cerebrovascular events. A recent meta-analysis found an increased risk
of recurrent stroke in clopidogrel- or aspirin-treated patients with ischemic
stroke who had high on-treatment platelet reactivity (HTPR). Few studies have
focused specifically on clopidogrel HTPR. Therefore, the aim of this study was to
examine the relationship between clopidogrel HTPR and recurrent ischemic events
in a population of Danish patients with IS. METHODS: We performed a prospective
observational study to evaluate the relationship between HTPR defined as platelet
reaction units >208 and a composite primary endpoint of recurrent stroke, TIA,
acute myocardial infarction (AMI), or vascular death over a 2-year follow-up
period. RESULTS: A total of 142 patients were included in the final statistical
analysis, but only 3 patients (2.1%) demonstrated clopidogrel HTPR. The median
time of on-treatment platelet testing was 75 days. Recurrent IS, TIA, AMI, or
vascular death occurred in 14 patients (10%). Of these, 1 new ischemic event
(AMI) occurred in a HTPR patient. There was no difference in the frequency of new
ischemic events between the HTPR and non-HTPR groups (P = .27); moreover, the
number of patients with HTPR was too small for statistical analysis. CONCLUSIONS:
Clopidogrel HTPR does not seem to be a major contributor to recurrent ischemic
events in Danish ischemic stroke patients.
PMID- 29945767
TI - Racial Difference in Cerebral Microbleed Burden Among a Patient Population in the
Mid-South United States.
AB - BACKGROUND: Although intracerebral hemorrhage (ICH) is more common among African
Americans, data on the burden of cerebral microbleeds (CMBs) among different
races is limited. The purpose of this study is to compare the number, associated
factors, and topography of CMBs between African-American and Caucasian
populations in the Mid-South United States. METHODS: Using natural language
processing, we extracted all brain MRIs performed during a 2-year period (2012
2013) when the report indicated the presence of CMB. All the extracted MRI
studies were evaluated for number and location of CMBs, prior stroke, and deep
white matter lesion. Negative binomial regression was used to model for the
overdispersed count data. RESULTS: A total 167 patients (mean age was 63 +/- 15
years, 49% men, 77% African-American, median CMB count: 8) with 1 or more CMBs on
their brain MRI were included in this study. There was no significant difference
between the 2 groups in terms of CMB locations (P = .086), but there was a
significant difference between African-American and Caucasian patients in terms
of number of CMBs (16.5 +/- 18 versus 6.5 +/- 5.5, P < .001). The prevalence of
multiple CMBs (CMBs >= 5) was similar among African-Americans and Caucasians (72%
versus 55%, P = .062). After adjusting for potential confounders, the African
American race was not independently associated with a higher CMB burden (P =
.073). CONCLUSION: African-American race was not independently associated with a
higher rate of CMB burden when compared to Caucasians after adjusting for
potential confounders. We also did not observe a significant racial difference
regarding the location and prevalence of multiple CMBs (CMBs >= 5).
PMID- 29945768
TI - Screening models for undiagnosed diabetes in Mexican adults using clinical and
self-reported information.
AB - BACKGROUND: Prevalence of diabetes in Mexico has constantly increased since 1993.
Since type 2 diabetes may remain undiagnosed for many years, identification of
subjects at high risk of diabetes is very important to reduce its impact and to
prevent its associated complications. OBJECTIVE: To develop easily implementable
screening models to identify subjects with undiagnosed diabetes based on the
characteristics of Mexican adults. SUBJECTS AND METHODS: Screening models were
developed using datasets from the 2006 and 2012 National Health and Nutrition
Surveys (NHNS). Variables used to develop the multivariate logistic regression
models were selected using a backward stepwise procedure. Final models were
validated using data from the 2000 National Health Survey (NHS). RESULTS: The
model based on the 2006 NHNS included age, waist circumference, and systolic
blood pressure as explanatory variables, while the model based on the 2012 NHNS
included age, waist circumference, height, and family history of diabetes. The
sensitivity and specificity values obtained from the external validation
procedure were 0.74 and 0.62 (2006 NHNS model) and 0.76 and 0.55 (2012 NHNS
model) respectively. CONCLUSIONS: Both models were equally capable of identifying
subjects with undiagnosed diabetes (~75%), and performed satisfactorily when
compared to other models developed for other regions or countries.
PMID- 29945770
TI - Follicular fluid vascular endothelial growth factor is associated with type of
infertility and interferon alpha correlates with endometrial thickness in natural
cycle in vitro fertilization.
AB - The aim of this study was to analyse the presence of vascular endothelial growth
factor (VEGF) and interferon alpha (IFN-alpha) in the follicular fluid (FF) and
their possible influence, as pro-angiogenic or anti-angiogenic factors, on in
vitro fertilization outcome. The concentrations of VEGF and IFN-alpha were
correlated with oocyte and embryo quality, concentrations of hormones in the
serum, perifollicular blood flow and endometrial thickness. VEGF was detected in
all FF samples (median 706.6 pg/ml, range 182.9-6638 pg/ml). IFN-alpha was
detected in 60% of the samples (median 6.5 pg/ml, range 0-79.4 pg/ml), while in
40% of the samples its levels were below the test detection limit. VEGF and IFN
alpha concentrations did not correlate with the cause of infertility,
concentrations of FSH, LH, E2 and prolactin, oocyte or embryo quality.
Significantly higher concentrations of VEGF have been found in women with primary
compared with secondary infertility (p = 0.011, Mann Whitney test). The
concentrations of VEGF and IFN-alpha did not correlate with the resistance index
(RI) on days of hCG administration, follicular aspiration and embryo transfer.
However, the concentrations of IFN-alpha correlated with endometrial thickness on
the day of embryo transfer (Spearman correlation coefficient rho = 0.4107; P <
0.05) but not on days of hCG administration and follicular aspiration. The
mechanism of VEGF association with the previous ability of having a child needs
to be clarified in future studies. The results of this study indicate a possible
role of IFN-alpha in pathways of endometrial remodelling.
PMID- 29945769
TI - Pharmacological characterization of nicotine-induced tremor: Responses to anti
tremor and anti-epileptic agents.
AB - We previously showed that nicotine evoked kinetic tremor by activating the
inferior olive, which is implicated in the pathogenesis of essential tremor, via
alpha7 nicotinic acetylcholine receptors. Here, we evaluated the effects of
various anti-tremor and anti-epileptic agents on nicotine-induced tremor in mice
to clarify the pharmacological characteristics of nicotine tremor. Drugs
effective for essential tremor, propranolol, diazepam and phenobarbital, all
significantly inhibited kinetic tremor induced by an intraperitoneal (i.p.)
injection of nicotine (1 mg/kg). In contrast, none of the medications for
Parkinson's disease, l-DOPA, bromocriptine or trihexyphenidyl, affected the
nicotine tremor. Among the anti-epileptic agents examined, valproate,
carbamazepine and ethosuximide, significantly inhibited nicotine-induced tremor.
In addition, a selective T-type Ca2+ channel blocker, TTA-A2, also suppressed the
nicotine tremor. However, neither gabapentin, topiramate, zonisamide nor
levetiracetam significantly affected nicotine-induced tremor. The present results
show that nicotine-induced tremor resembles essential tremor not only on the
neural basis, but also in terms of the pharmacological responses to anti-tremor
agents, implying that nicotine-induced tremor can serve as a model for essential
tremor. In addition, it is suggested that anti-epileptic agents, which have
stimulant actions on the GABAergic system or blocking actions on voltage-gated
Na+ channels and T-type Ca2+ channels, can alleviate essential tremor.
PMID- 29945771
TI - Needs Assessment for an American College of Surgeons Certificate in Applied
Surgical Education Leadership (CASEL).
AB - OBJECTIVE: Surgeon educators in departments of surgery play key roles in leading
and advancing surgical education. Their activities include ensuring sound
curricula and evaluation systems, monitoring education resources, overseeing
faculty development, and providing mentorship. For more than 25 years, the
American College of Surgeons (ACS) has offered a comprehensive "Surgeons as
Educators" (SAE) course to address fundamental topics in surgical education. This
study aims to identify future career needs of SAE graduates to inform the
development of an American College of Surgeons Certificate in Applied Surgical
Education Leadership program. DESIGN: An IRB exempt, anonymous electronic survey
was developed to determine educational roles, career aspirations, and needs of
SAE Graduates. SETTING AND PARTICIPANTS: Participants included all 763 1993-2016
SAE graduates. RESULTS: One hundred and thirty-five responses were received from
600 (22.5%) graduates with valid email addresses. Sixty (45%) respondents
completed the SAE Course > 5 years prior to the study (M5YRS) and 75 (55%) within
the last 5 years (L5YRS). L5YRS respondents were less likely to be full
professors (8% vs. 44%) or to serve as program directors (32% vs. 57%), and more
likely to be associate program directors (25% vs. 17%) or clerkship directors
(40% vs. 18%). High percentages of both L5YRS and M5YRS reported not pursuing
additional educational opportunities post-SAE due to time and fiscal constraints.
One-fifth of respondents were unaware of additional opportunities and 19% of
M5YRS versus 6% of L5YRS stated that existing programs did not meet their needs.
Overall improving skills as educational leaders, developing faculty development
programs, and conducting educational research were noted as priorities for future
development. Differences were observed between the L5YRS and M5YRS groups. The
dominant preferences for course format were full-time face-to-face (41%) or a
combination of full-time face-to-face with online modules (24%). The most
important considerations in deciding to pursue a certificate course were course
content, and interest in advancing career and time constraints. CONCLUSIONS: An
SAE graduate survey has confirmed the need for additional formal training in
surgical education leadership in order to permit surgeon educators meet the
demands of the changing landscape of surgical education. The needs of early
career faculty may differ from those of more senior surgeon educators.
PMID- 29945772
TI - Diabetes in pregnancy and infant mortality: Link with glycemic control.
AB - AIMS: To compare the clinical and glycemic profile as well as pregnancy
complications and infant mortality among diabetic mothers in Indonesia. MATERIALS
AND METHODS: Data was obtained from medical records of Internal-Medicine Clinic
in Hermina Podomoro General Hospital during the period January-December 2015.
Subjects were grouped into good and poor outcome groups based on infant
mortality. RESULTS: Forty-five subjects were obtained with an average age of 31
years, 41 had gestational diabetes mellitus while 4 had pregestational diabetes.
Twenty-one patients had high-risk pregnancies (age >30 years or <20 years). No
maternal mortalities were reported, only 6 pregnancies were complicated with
infant death. Comorbidities mainly found were preeclampsia, anemia and urinary
tract infection. Most patients delivered through caesarian section. Almost all of
them were treated with insulin. Comparison between both groups showed that those
with poor outcomes have a significantly higher body mass index prior to
pregnancy, higher body weight prior and after pregnancy as well as worse glycemic
profile. CONCLUSION: Diabetes in pregnancy has been found to increase rates of
infant mortality. This study showed that patients with poor glycemic control are
at a greater risk of infant mortality. Therefore increased monitoring and
prenatal care as well as optimal glycemic control for patients with diabetes in
pregnancy is recommended. Optimal glycemic control will lead to diabetic mothers
with pregnancies of equal risk and similar outcomes to those of normal patients.
PMID- 29945773
TI - Asking different questions: A call to action for research to improve the quality
of care for every woman, every child.
PMID- 29945774
TI - Informational interventions on paternal outcomes during the perinatal period: A
systematic review.
AB - PROBLEM: The perinatal period is a stressful transition for new parents.
BACKGROUND: Various forms of educational interventions are available and are
found to be efficacious in improving maternal and child outcomes. Such
interventions for fathers were scarce and western-centric. Fathers should be
educated as they have an impact on maternal and child outcomes. AIM: This review
aims to evaluate the efficacy of quantitatively-studied informational support
focused interventions for fathers using paternal outcomes only. METHODS: The
search was carried out in six databases: Cumulative Index to Nursing and Allied
Health Literature, PubMed, Scopus, Embase, Psychological Information Database,
and MedNar. Cochrane Collaboration's tools were used to assess the eligibility of
the studies. FINDINGS: A total of 17 studies with 18 interventions were
identified and included in the narrative synthesis. Most interventions were
delivered to the Western population during the antenatal or postpartum period.
The method of delivery for these interventions was mainly face-to-face, with
inconclusive findings on various paternal psychosocial outcomes. DISCUSSION:
Limited father-inclusive interventions were available. Technology-based
longitudinal studies with interventions carried out across the perinatal period
with longer follow-up periods were recommended for interventions providing
informational support for fathers. Future studies can also examine paternal
physical health and behavioural outcomes. Interventions in culturally-diverse
populations should be designed and tested for their efficacies as fathers have
different informational needs, especially in Asia. CONCLUSION: Informational
interventions for fathers were found to be lacking and recommendations for future
studies on educational interventions for fathers were discussed.
PMID- 29945775
TI - Aerobic training reduces blood pressure and waist circumference and increases HDL
c in metabolic syndrome: a systematic review and meta-analysis of randomized
controlled trials.
AB - The objective of this study is to estimate the effect of aerobic training (AT) on
metabolic syndrome (MetS) outcomes. The Medline, EMBASE, SPORTDiscus, The
Cochrane Library, and PEDro databases were searched from inception to May 2017.
Two independent reviewers selected the studies and assessed their quality and
data. The pooled mean differences between intervention groups and the control
group were calculated using a random-effect model. Only randomized controlled
trials that compared the effect of AT on MetS with a control group were included.
Seventeen published studies were included in the meta-analysis. Systolic and
diastolic blood pressure were significantly reduced (-5.11 mmHg [95% confidence
interval [CI] -7.36, -2.85] and -2.97 mmHg [-4.99, -0.94], respectively),
following AT. There was also a significant reduction in waist circumference (
2.18 cm [95% CI -3.75, -0.62]) and a significant increase in high-density
lipoprotein cholesterol (95% CI -3.15 mg/dL [-5.30, -1.01]). The pooled effect
showed a reduction of -7.64 mg/dL [95% CI -17.65, 2.37] in triglycerides and
1.36 mg/dL [95% CI -4.11, 1.40] in fasting glucose. This systematic review and
meta-analysis provides an overview of the evidence supporting AT as an effective
approach to reduce blood pressure levels and waist circumference and increase
high-density lipoprotein cholesterol levels. These changes may help to reduce the
risk of stroke mortality and mortality from heart disease in people with MetS.
PMID- 29945776
TI - Short-term exposure to dexamethasone promotes autonomic imbalance to the heart
before hypertension.
AB - Hypertension is one of the chronic side effects of dexamethasone (DEX) treatment;
however, almost nothing is known about its acute effects. Therefore, the aim of
this study was to investigate the possible mechanisms involved in blood pressure
control after acute or short-term DEX treatment in adult animals. Eighty Wistar
rats were divided into four groups: C1 and C5, for rats treated with saline for 1
or 5 days, respectively; D1 and D5, for rats treated with DEX for 1 or 5 days,
respectively (decadron, 1 mg/kg, i.p.). Heart rate was increased in DEX
treatment, but arterial pressure and cardiac muscle mass were not altered. Only
few and isolated changes on gene expression and protein level of renin
angiotensin system components were observed. Five days of DEX treatment, but not
one day, determined an increase in sympathetic component of spectral analysis
(+75.93%, P < .05) and a significant reduction of parasympathetic component (
18.02%, P < .05), which contributed to the autonomic imbalance to the heart
(LF/HF, +863.69%). The results of this present study demonstrated, for the first
time, that short-term exposure to DEX treatment impairs the autonomic balance to
the heart before hypertension, which was independent of renin-angiotensin system.
PMID- 29945777
TI - Electrocardiographic confirmation of a twin pregnancy in a mare at 8 months of
gestation.
AB - A 15-year-old Warmblood mare, at 8 months of gestation, was presented to the
Ghent University Faculty of Veterinary Medicine for evaluation of suspected stage
one labor. Transrectal ultrasonography revealed no clear signs of placentitis or
stage one labor. The combined thickness of uterus and placenta was 11 mm and the
cervix was closed. Twin pregnancy was suspected by transabdominal ultrasonography
but could not be confirmed with certainty. An electrocardiogram (ECG) was
recorded from the mare's abdominal wall to register a fetal ECG. To confirm twin
pregnancy, registration of both fetal ECGs simultaneously on the same ECG trace
was attempted. Twelve different electrode configurations were used. In 11
recordings, one fetal ECG was visible. Only one specific right-sided electrode
configuration showed both fetal ECGs at the same time, which confirmed twin
pregnancy. Although electrocardiographic diagnosis of a twin pregnancy in a mare
is possible, this case highlights the need for multiple electrode configurations
and the high likelihood of false negatives.
PMID- 29945778
TI - Estimating the effective reproduction number of dengue considering temperature
dependent generation intervals.
AB - The effective reproduction number, Rt, is a measure of transmission that can be
calculated from standard incidence data to timely detect the beginning of
epidemics. It has being increasingly used for surveillance of directly
transmitted diseases. However, current methods for Rt estimation do not apply for
vector borne diseases, whose transmission cycle depends on temperature. Here we
propose a method that provides dengue's Rt estimates in the presence of
temperature-mediated seasonality and apply this method to simulated and real data
from two cities in Brazil where dengue is endemic. The method shows good
precision in the simulated data. When applied to the real data, it shows
differences in the transmission profile of the two cities and identifies periods
of higher transmission.
PMID- 29945779
TI - PCSK9 monoclonal antibody on a knife-edge: An article of faith in FH?
PMID- 29945780
TI - Creatine supplementation does not alter the creatine kinase response to eccentric
exercise in healthy adults on atorvastatin.
AB - BACKGROUND: Serum creatine kinase (CK) levels are higher after eccentric, muscle
damaging exercise in statin-treated patients. This could contribute to the
increased statin-associated muscle symptoms reported in physically active
individuals. OBJECTIVE: We tested the hypothesis in this pilot study that
creatine (Cr) monohydrate supplementation would reduce the CK response to
eccentric exercise in patients using statins to determine if Cr supplementation
could be a strategy to mitigate statin-associated muscle symptoms in physically
active individuals. METHODS: Healthy, nonsmoking men (n = 5) and women (n = 14)
were randomized to Cr monohydrate = atorvastatin 80 mg + 10 g Cr monohydrate (n =
10, age = 60 +/- 7 years) or to placebo (PL) = atorvastatin 80 mg + PL (n = 9,
age = 52 +/- 6 years). After 4 weeks of treatment, subjects performed 45 minutes
of eccentric exercise (downhill walking at a -15% grade). Serum CK levels, muscle
soreness (visual analog scale after two squats), and muscle pain severity and
interference (using the brief pain inventory) were measured before and after 4
weeks of treatment, and then for 4 consecutive days after downhill walking.
Vitamin D, or serum 25(OH)D, was also measured at baseline. RESULTS: The PL group
was younger (P = .01) but not otherwise different in blood lipids, vitamin D, CK,
muscle visual analog scale, and pain scores before (all P > .21) or after (all P
> .12) treatment. CK increased in all subjects after downhill walking (P < .01),
but neither the relative peak change (expressed as group mean difference with 95%
confidence intervals: 43.52% [-196.41, 283.45]) nor the absolute peak change
(67.38 U/L [-121.55, 256.31]) relative to baseline was different between groups
(P = .46 and .71, respectively). A similar lack of treatment effect was observed
for muscle soreness (11.03 mm [-9.49, 31.55]), pain severity (0.77 pts [-0.95,
2.50]), and pain interference (1.02 pts [-1.25, 3.29]) with P-values for group
comparisons = 0.27, 0.36, and 0.35, respectively. However, subjects with
"insufficient" Vitamin D < 30 ng/mL (n = 10) had an ~2-fold greater CK increase
with eccentric exercise (nominal P-value = .04) than subjects with higher vitamin
D levels. CONCLUSION: Cr monohydrate did not reduce CK increases after exercise
in statin-treated subjects. We did observe that low vitamin D levels are
associated with a greater CK response to eccentric exercise in statin-treated
subjects.
PMID- 29945781
TI - Revised cardiac risk index poorly predicts cardiovascular complications after
adhesiolysis for small bowel obstruction.
AB - BACKGROUND: The number of patients undergoing preoperative risk stratification in
the United States is expected to increase as the population ages. A large
percentage of patients undergo some form of preoperative testing, and society
guidelines suggest that up to 50% of the testing in lower risk surgical subgroups
is unnecessary. The Revised Cardiac Risk Index and the risk calculator of the
American College of Surgeons National Surgical Quality Improvement Program are
widely used tools as the first step of preoperative cardiac evaluation. The
Revised Cardiac Risk Index was developed to fill a need for objective
perioperative cardiac risk evaluation. Despite the ease of use of Revised Cardiac
Risk Index, it is uncertain if the stratification is accurate for surgical
patients because its accuracy in large surgical samples has not been tested. With
the National Surgical Quality Improvement Program risk calculator having
excellent accuracy in estimating cardiac complications (area under the receiver
operating characteristic 0.895), a unique opportunity to test the predictive
accuracy of postsurgical cardiac events became available. The purpose of this
study is to determine the accuracy of the Revised Cardiac Risk Index for
predicting cardiovascular complications after adhesiolysis for small bowel
obstruction. METHODS: From 2005 to 2015, 34,032 cases of open or laparoscopic
adhesiolysis (Current Procedural Terminology codes 44005 and 44180) for small
bowel obstruction (International Classification of Diseases, 10th edition [ICD
10]) were analyzed using the National Surgical Quality Improvement Program
dataset. Revised Cardiac Risk Index estimates were calculated for each case and
compared to reported cardiovascular complications (myocardial infarction or
cardiac arrest) using univariable logistic regression. Overall predictive
accuracy was assessed by measuring model discrimination (area under the receiver
operating characteristic) and model calibration (Hosmer-Lemeshow chi-squared
statistics). RESULTS: Although the Revised Cardiac Risk Index predicted
cardiovascular complications with an odds ratio of 2.3 and a 95% confidence
interval of 1.9 to 2.8 (P < .001) and the Hosmer-Lemeshow chi-square was
significant (0.22, P = 0.64), the area under the receiver operating
characteristic was poor (0.63, 95% confidence interval 0.59-0.67). CONCLUSION:
Despite its relative simplicity, the Revised Cardiac Risk Index performed poorly
as a predictor of cardiovascular complications after adhesiolysis for small bowel
obstruction. These findings question the utility of the Revised Cardiac Risk
Index in this patient population. Future studies should aim to develop models
that are computationally simple while retaining predictive accuracy.
PMID- 29945782
TI - Opportunistic salpingectomy to decrease the mortality from ovarian cancer: Can we
expand the pool of eligible patients?
PMID- 29945783
TI - Are surgeons reluctant to accurately report intraoperative adverse events? A
prospective study of 1,989 patients.
AB - BACKGROUND: The true incidence of intraoperative adverse events (iAEs) remains
unknown. METHODS: All patients undergoing abdominal surgery at an academic
institution between January and July 2016 were included in a prospective fashion.
At the end of surgery, using a secure REDCap database, the surgeon was given the
Institute of Medicine definition of intraoperative adverse events and asked
whether an intraoperative adverse event had occurred. Blinded reviewers
systematically examined all operative reports for intraoperative adverse events
and their severity. The response rate and the intraoperative adverse event rate
reported by surgeons were calculated. The latter was compared with the rate of
intraoperative adverse events detected by operative report review. The severity
of intraoperative adverse events was assessed based on a previously validated
intraoperative adverse event classification system. RESULTS: A total of 1,989
operations were included. The surgeons' response rate was 71.9%, reporting
intraoperative adverse events in 107 operations (7.5%). Of those intraoperative
adverse events, 26 (24.3%) were not described in the operative report. Operative
report review revealed intraoperative adverse events in 417 operations (21.0%).
Most injuries were of lower severity (85.8% were either class I or II). The
surgeons' response rate was similar in operations with and without intraoperative
adverse events (69.8% versus 72.5%, P=.28), but they underreported low severity
intraoperative adverse events-only 13.2% of class I compared with 35.3%, 36.8%,
and 55.6% of injury classes II, III, and IV respectively (P<.001). CONCLUSION:
Surgeons are willing to report intraoperative adverse events, but systematically
and significantly underreport them, especially if they are of lower severity.
This is potentially related to the absence of a clear intraoperative adverse
event definition or their personal interpretation of their clinical significance.
PMID- 29945784
TI - Aging effects on the Achilles tendon moment arm during walking.
AB - The Achilles tendon (AT) moment arm transforms triceps surae muscle forces into a
moment about the ankle which is critical for functional activities like walking.
Moreover, the AT moment arm changes continuously during walking, as it depends on
both ankle joint rotation and triceps surae muscle loading (presumably due to
bulging of the muscle belly). Here, we posit that aging negatively effects the
architecturally complex AT moment arm during walking, which thereby contributes
to well-documented reductions in ankle moment generation during push-off. We used
motion capture-guided ultrasound imaging to quantify instantaneous variations in
the AT moment arms of young (23.9 +/- 4.3 years) and older (69.9 +/- 2.6 years)
adults during walking, their dependence on triceps surae muscle loading, and
their association with ankle moment generation during push-off. Older adults
walked with 11% smaller AT moment arms and 11% smaller peak ankle moments during
push-off than young adults. Moreover, as hypothesized, these unfavourable changes
were significantly and positively correlated (r2 = 0.38, p < 0.01). More
surprisingly, aging attenuated load-dependent increases in the AT moment arm
(i.e., those between heel-strike and push-off at the same ankle angle); only
young adults exhibited a significant increase in their AT moment arm due to
triceps surae muscle-loading. Age-associated reductions in triceps surae volume
or activation, and thus muscle bulging during force generation, may compromise
the mechanical advantage of the AT during the critical push-off phase of walking
in older adults. Thus, strategies to restore and/or improve locomotor performance
in our aging population should consider these functionally important changes in
musculoskeletal behavior.
PMID- 29945785
TI - Coordination of lower extremity multi-joint control strategies during the golf
swing.
AB - This study aimed to understand how players coordinate the multi-joint control
strategies of the rear and target legs to satisfy the lower extremity and whole
body mechanical objectives during the golf swing when hitting shots with
different clubs. Highly skilled golf players (n = 10) performed golf swings with
a 6-iron and a driver. Joint kinetics were calculated using ground reaction
forces and segment kinematics to determine net joint moments (NJMs) during the
interval of interest within the downswing. Between club difference in NJMs and 3D
support moments were compared across the group and within a player. Although
player-specific multi-joint control strategies arose, players generally increased
target leg ankle, knee, and hip NJMs when hitting with the driver while
maintaining the relative contribution to the 3D support moment. Multi-joint
control strategies used to control the target and rear legs were found to be
different, yet the majority of the 3D support moment was produced by NJMs about
an axis perpendicular to the leg planes. These results emphasize the importance
of recognizing how an individual player coordinates multi-joint control from each
leg, and highlights the need to design interventions that are player and leg
specific to aid in improving player performance.
PMID- 29945786
TI - Estimation of vertical ground reaction force during running using neural network
model and uniaxial accelerometer.
AB - Wearable technology has been viewed as one of the plausible alternatives to
capture human motion in an unconstrained environment, especially during running.
However, existing methods require kinematic and kinetic measurements of human
body segments and can be complicated. This paper investigates the use of neural
network model (NN) and accelerometer to estimate vertical ground reaction force
(VGRF). An experimental study was conducted to collect sufficient samples for
training, validation and testing. The estimated results were compared with VGRF
measured using an instrumented treadmill. The estimates yielded an average root
mean square error of less than 0.017 of the body weight (BW) and a cross
correlation coefficient greater than 0.99. The results also demonstrated that NN
could estimate impact force and active force with average errors ranging between
0.10 and 0.18 of BW at different running speeds. Using NN and uniaxial
accelerometer can (1) simplify the estimation of VGRF, (2) reduce the
computational requirement and (3) reduce the necessity of multiple wearable
sensors to obtain relevant parameters.
PMID- 29945787
TI - Mining the acidic serum proteome utilizing off-gel isoelectric focusing and label
free quantitative liquid chromatography mass spectrometry.
AB - Serum remains an attractive source for the discovery of disease related
biomarkers due to its intimate interaction with the majority of tissues within
the body. The dynamic range of proteins present within serum has long complicated
the ability to detect low level tissue leakage proteins that offer more promise
as potential biomarkers due to their higher degree of specificity. Depletion
strategies, using affinity based sorbents, to remove the most abundant serum
proteins are routinely used for matrix simplification during discovery strategies
focused on the serum proteome or glycoproteome. Glycoproteins bearing glycans
with terminal sialic acid residues have been shown to be differentially expressed
in a variety of cancers and are of interest due to the varied involvement of
sialic acid in biological functions related to cancer development and metastasis.
Herein, we describe the use of 14P serum depletion with subsequent off-gel
isoelectric focusing using narrow pH range acidic strips, to facilitate
simplification and enrichment of the acidic proteome and glycoproteome prior to
label free liquid chromatography mass spectrometry (LC-MS) based proteomic
analysis. The developed platform enabled the detection of proteins present within
serum at sub-nanomolar concentrations while data analysis using a variety of
bioinformatics resources suggested that many of the detected proteins were tissue
leakage proteins or proteins associated with specific cellular compartments,
rather than traditional secreted proteins. Comparison with theoretical
isoelectric point (pI) values also revealed that some detected proteins had
higher pI values than the separation range applied during the IEF step,
suggesting that their presence may be due to glycans with high degrees of
sialylation being attached to the protein backbone, as well as the presence of
other post translational modifications. Such findings agree with offline glycomic
profiling of the IEF fractions wherein increasing degrees of sialylation were
detected across the pH strip from the basic towards the acidic end. Application
of the platform using pooled serum from patients bearing gastric cancer, both
before and after surgical intervention for tumour removal, revealed a number of
differentially expressed proteins associated with cell recognition and cell
signalling. The developed platform enabled excellent sensitivity and offers
strong potential for application within biomarker discovery studies focused on
the acidic proteome.
PMID- 29945788
TI - A fast and selective method for the determination of 8 carcinogenic polycyclic
aromatic hydrocarbons in rubber and plastic materials.
AB - Polycyclic Aromatic Hydrocarbons (PAHs) have been detected in rubber and plastic
components of a number of consumer products such as toys, tools for domestic use,
sports equipment, and footwear, with carbon black and extender oils having been
identified as principal sources. In response to these findings, the European
Union Regulation (EU) No. 1272/2013 was adopted in December 2013, amending entry
50 in Annex XVII to the Registration, Evaluation, Authorisation, and Restriction
of Chemicals (REACH) directive establishing a restriction on the content of eight
individual carcinogenic PAHs in plastic and rubber parts of products supplied to
the public. This work proposes a simple, relatively fast, and cost effective
method for determining the concentrations of each of these eight carcinogenic
PAHs for compliance testing. Existing methodologies were taken as a starting
point, improving in particular the extraction and the clean-up procedures.
Randall hot extraction and ultrasonic extraction were compared with regard to
their extraction efficiency. Randall hot extraction proved to be more efficient
(10-40%, depending on PAH). Sample extract clean-up performance was qualitatively
assessed for silica-packed columns and molecularly imprinted polymers (MIPs)
solid phase extraction (SPE) cartridges. The use of highly selective MIP-SPE
cartridges removed most of the undesired contaminants, highlighting their
superiority with regard to traditional, silica-based purification methodologies.
The introduction of Randall-hot extraction for sample extraction and MIP-based
solid phase extraction cartridges for selective clean-up represents a novel
advance compared with previously reported methods in this field. In combination
with gas chromatography-mass spectrometry (GC-MS) analyses in selected ion mode,
the method was found to be excellent in terms of extraction efficiency, extract
purity, and speed.
PMID- 29945789
TI - Sensitive and selective gas chromatography-tandem mass spectrometry method for
the detection of nitrobenzene in tobacco smoke.
AB - Nitrobenzene, a potentially harmful compound found in tobacco smoke, has been
largely excluded from prior analysis due to difficulties with quantification.
Quantifying harmful compounds in cigarette smoke is useful to compare products,
to examine the impact of design parameters on delivery, and to help estimate
exposures. A sensitive high-throughput method has been developed for quantifying
nitrobenzene in machine-generated mainstream cigarette smoke using isotope
dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS). This method
has sufficient sensitivity to measure vapor phase nitrobenzene concentrations in
the low nanogram range, with a 418 pg/cig method limit of detection. Precision
estimates from two quality control cigarette products resulted in percent
relative standard deviations of 11.5% and 14.9%; product variability estimates
from 13 cigarette products resulted in percent relative standard deviations
ranging from 2.8% to 16.9%. Nitrobenzene in the machine-generated, mainstream
smoke from 15 cigarette products are reported and range from 18 to 38 ng/cig
under the Health Canada Intense smoking regimen.
PMID- 29945790
TI - Profiling of N-linked glycans from 100 cells by capillary electrophoresis with
large-volume dual preconcentration by isotachophoresis and stacking.
AB - Glycan structure is changed in response with pathogenesis like cancer. Profiling
of glycans from limited number of pathogenetic cells in an early-stage tissue is
essential for discovering effective drugs. For analyzing tiny biological samples,
we developed sensitive, high-resolution, and salt-tolerant method for analyzing
trace level of N-linked glycans by coupling capillary electrophoresis (CE), laser
induced fluorescence (LIF) detection, and a new online sample preconcentration
(OSP) method named "large-volume dual preconcentration by isotachophoresis and
stacking (LDIS)", which is composed of two OSP methods, large-volume sample
stacking (LVSS) and transient isotachophoresis (tITP). A typical LDIS-CE-LIF
protocol was simple: a short-plug of leading electrolyte (LE) and large-volume
sample solution were introduced to a capillary, followed by application of
constant voltage. In the analysis of glucose ladder labeled with 8-aminopyrene
1,3,6-trisulfonic acid with 10 mM sodium chloride as LE, up to 2300-fold
sensitivity increase was achieved with higher resolution than those in normal CE.
By applying pressure assist during preconcentration, both viscous gel electrolyte
and salty matrix of up to 10 mM NaCl were acceptable. Finally, N-glycans from
approximately 100 cells (HeLa, MCF7, and HepG2) were analyzed as the model of
localized tumor cells. From 30 to 40 glycans were successfully detected with
almost same profile of large-scale sample. N-glycan structure could be predicted
by searching glucose-unit value via Glycobase database, indicating that HepG2
expressed more sialylated glycans and MCF-7 expressed less glycans respectively,
comparing with HeLa cells. It suggests the potential of LDIS-CE-LIF for discovery
of disease-specific N-linked glycans in microscale environment.
PMID- 29945791
TI - Sensorimotor mu-alpha power is positively related to corticospinal excitability.
AB - BACKGROUND: Alpha (8-14 Hz) oscillatory power is linked to cortical excitability
and corresponding modulations of sensory evoked potentials and perceptual
detection performance. In somatosensory cortex (S1), negative linear and inverted
U-shape relationships exist, whereas its effect on the primary motor cortex (M1)
is hardly known. OBJECTIVE: We used real-time EEG-triggered transcranial magnetic
stimulation (TMS) of M1 to characterize the relationship between spontaneous
sensorimotor mu-alpha power fluctuations at rest and corticospinal excitability.
METHODS: In 16 subjects, mu-alpha power was continuously monitored over the left
sensorimotor cortex, and each 10%-percentile bin of the individual mu-alpha power
distribution was repeatedly targeted in pseudorandomized order by single-pulse
TMS of left M1, measuring motor evoked potentials (MEP) in the contralateral
hand. RESULTS: We found a weak positive relationship between mu-alpha power and
MEP amplitude. CONCLUSION: Sensorimotor mu-alpha power may reflect a net
facilitation or disinhibition of M1, possibly resulting from mu-alpha based
suppression of excitatory and inhibitory input from S1.
PMID- 29945792
TI - Transient aphasia after right-unilateral ultrabrief electroconvulsive therapy: A
case report.
AB - A brief period of aphasia is an extremely rare and likely underreported adverse
effect of electroconvulsive therapy. Clinical studies that have described this
phenomenon are scarce and its prevalence is unknown. We present a unique case of
a 35-year old woman, who underwent an outpatient ECT session at our department,
followed by a short span of aphasic symptoms, the extent of which were monitored
clinically and via the czech version of the Minnesota aphasia screening test.
PMID- 29945793
TI - Phosphorus-containing isothiocyanate-derived mercapturic acids as a useful
alternative for parental isothiocyanates in experimental oncology.
AB - A series of phosphonates, phosphinates and phosphine oxides isothiocyanate
derived mercapturic acids were synthesized. A temperature dependence dynamic
proton decoupled 31P NMR studies indicated that in most cases the compounds were
obtained as a mixture of rotamers. Moreover, biologically relevant reversibility
of mercapturic acids synthesis from the parental isothiocyanates was confirmed.
All compounds were evaluated ashighly active antiproliferative agents in vitro in
human colon cancer cell lines (LoVo and its doxorubicin-resistant subline
LoVo/DX). The cell cycle progression and caspase-3 activity analyses revealed
compounds moderate activity as apoptosis inducers and their poor influence on
cell cycle progression in the LoVo cells. Our results confirm that isothiocyanate
derived mercapturic acids present a reasonable alternative for the parental
compounds, and can replace them in the future studies on isothiocyanates
potential as anticancer agents.
PMID- 29945794
TI - ROCK inhibitors 2. Improving potency, selectivity and solubility through the
application of rationally designed solubilizing groups.
AB - Solubilizing groups have been frequently appended to kinase inhibitor drug
molecules when solubility is insufficient for pharmaceutical development. Such
groups are usually located at substitution sites that have minimal impact on
target activity. In this report we describe the incorporation of solubilizing
groups in a class of Rho kinase (ROCK) inhibitors that not only confer improved
solubility, but also enhance target potency and selectivity against a closely
related kinase, PKA.
PMID- 29945795
TI - Merging of ruxolitinib and vorinostat leads to highly potent inhibitors of JAK2
and histone deacetylase 6 (HDAC6).
AB - Inhibition of more than one pathway in a cancer cell with a single molecule could
result in better therapies with less complex dosing regimens. In this work multi
component ligands have been prepared by joining together key pharmacophores of
two different enzyme inhibitors in a way which increases potency against the
individual pathways. Selective JAK1/2 inhibitor, ruxolitinib (3), and pan-HDAC
inhibitor vorinostat (4) were linked together by a single nitrogen atom to create
a new series of compounds with very potent JAK2 and HDAC6 inhibition with
selectivity against HDAC1. A preferred compound, 13b, had unprecedented sub
nanomolar JAK2 potency with an IC50 of 41 pM and a sub-nanomolar IC50 against
HDAC6 of 200 pM. Binding models show a good fit into both JAK2 and HDAC6.
PMID- 29945796
TI - Fluorescent-fipronil: Design and synthesis of a stable conjugate.
AB - Fipronil is a phenyl pyrazole molecule widely used across the world as both
insecticide and veterinary drug. The main goal of this work was to synthesize a
fluorescently labeled fipronil derivative for cellular imaging without affecting
its intrinsic properties. We selected fluorescein as fluorescent probe and we
investigated different strategies for stable chemical ligation between both
entities, such as thiourea and direct peptide bond. While thiourea bond displayed
low stability, direct peptide bond was difficult to achieve due to problems of
steric hindrance. The best result was obtained by conjugation using click
chemistry, which allowed to obtain fipronil stably labeled with the fluorescent
probe.
PMID- 29945797
TI - Impact of crystallization firing process on the microstructure and flexural
strength of zirconia-reinforced lithium silicate glass-ceramics.
AB - OBJECTIVES: The aim of this study was to characterize the microstructure of two
zirconia-reinforced lithium silicate (ZLS) glass-ceramics and evaluate their
mechanical properties before and after the crystallization firing process (CFP).
METHODS: Field emission-scanning electron microscope (FE-SEM) and energy
dispersive X-ray spectroscopy (EDS) analyses were performed for microstructural
characterization. To evaluate the pattern of crystallization and the molecular
composition of ZLS glass-ceramics, was used X-ray diffraction (XRD). Vickers
hardness, fracture toughness by the indentation method, and biaxial flexural
strength were also measured. One hundred and forty ceramic discs were produced
(diameter=12mm; thickness=1.2mm) and allocated among four groups (n=30): Sfir,
Sunf-ZLS Vita Suprinity; and Cfir and Cunf-ZLS Celtra Duo; fired and unfired,
respectively. Statistical analysis was performed and Weibull failure
probabilities were calculated. RESULTS: Cfir showed the highest characteristic
strength (251.25MPa) and hardness (693.333+/-10.85GPa). Conversely, Sunf
presented the lowest characteristic strength (106.95MPa) and significantly lowest
hardness (597.533+/-33.97GPa). According to Weibull analysis, Sunf had the
highest structural reliability (m=7.07), while Sfir presented the lowest
(m=5.38). The CFP was necessary to crystallize zirconia in the partially
crystallized ZLS glass-ceramics. Sfir had a lower percentage of crystallized
zirconia than did Cfir. Fractographic analyses showed that all failures initiated
from an inherent critical defect in Sunf and from processing defects in the
remaining groups. SIGNIFICANCE: The CFP had a direct influence on the flexural
strength and microstructural characteristics of both ZLS materials.
PMID- 29945798
TI - Should adhesive debonding be simulated for intra-radicular post stress analyses?
AB - OBJECTIVE: Elucidate the influence of debonding on stress distribution and
maximum stresses for intra-radicular restorations. METHODS: Five intra-radicular
restorations were analyzed by finite element analysis (FEA): MP=metallic cast
post core; GP=glass fiber post core; PP=pre-fabricated metallic post core;
RE=resin endocrowns; CE=single piece ceramic endocrown. Two cervical preparations
were considered: no ferule (f0) and 2mm ferule (f1). The simulation was conducted
in three steps: (1) intact bonds at all contacts; (2) bond failure between crown
and tooth; (3) bond failure among tooth, post and crown interfaces. Contact
friction and separation between interfaces was modeled where bond failure
occurred. Mohr-Coulomb stress ratios (sigmaMC ratio) and fatigue safety factors
(SF) for dentin structure were compared with published strength values, fatigue
life, and fracture patterns of teeth with intra-radicular restorations. RESULTS:
The sigmaMC ratio showed no differences among models at first step. The second
step increased sigmaMC ratio at the ferule compared to step 1. At the third step,
the sigmaMC ratio and SF for f0 models were highly influenced by post material.
CE and RE models had the highest values for sigmaMC ratio and lower SF. MP had
the lowest sigmaMC ratio and higher SF. The f1 models showed no relevant
differences among them at the third step. SIGNIFICANCE: FEA most closely
predicted failure performance of intra-radicular posts when frictional contact
was modeled. Results of analyses where all interfaces are assumed to be perfectly
bonded should be considered with caution.
PMID- 29945799
TI - A Schlemm Canal Microstent for Intraocular Pressure Reduction in Primary Open
Angle Glaucoma and Cataract: The HORIZON Study.
AB - OBJECTIVE: To compare cataract surgery with implantation of a Schlemm canal
microstent with cataract surgery alone for the reduction of intraocular pressure
(IOP) and medication use after 24 months. DESIGN: Prospective, multicenter,
single-masked, randomized controlled trial. PARTICIPANTS: Subjects with
concomitant primary open-angle glaucoma (POAG), visually significant cataract,
and washed-out modified diurnal IOP (MDIOP) between 22 and 34 mmHg. METHODS:
Subjects were randomized 2:1 to receive a single Hydrus Microstent (Ivantis, Inc,
Irvine, CA) in the Schlemm canal or no stent after uncomplicated
phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week,
and 1, 3, 6, 12, 18, and 24 months postoperatively. Medication washout and MDIOP
measurement were repeated at 12 and 24 months. MAIN OUTCOME MEASURES: The primary
and secondary effectiveness end points were the proportion of subjects
demonstrating a 20% or greater reduction in unmedicated MDIOP and change in mean
MDIOP from baseline at 24 months, respectively. Hypotensive medication use was
tracked throughout the course of follow-up. Safety measures included the
frequency of surgical complications and adverse events. RESULTS: A total of 369
eyes were randomized after phacoemulsification to Hydrus Microstent (HMS) and 187
to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by >=20% in
77.3% of HMS group eyes and in 57.8% of NMS group eyes (difference = 19.5%, 95%
confidence interval [CI] 11.2%-27.8%, P < 0.001). The mean reduction in 24-month
unmedicated MDIOP was -7.6+/-4.1 mmHg (mean +/- standard deviation) in the HMS
group and -5.3+/-3.9 mmHg in the NMS group (difference = -2.3 mmHg; 95% CI, -3.0
to -1.6; P < 0.001). The mean number of medications was reduced from 1.7+/-0.9 at
baseline to 0.3+/-0.8 at 24 months in the HMS group and from 1.7+/-0.9 to 0.7+/
0.9 in the NMS group (difference = -0.4 medications; P < 0.001). There were no
serious ocular adverse events related to the microstent, and no significant
differences in safety parameters between the 2 groups. CONCLUSIONS: This 24-month
multicenter randomized controlled trial demonstrated superior reduction in MDIOP
and medication use among subjects with mild-to-moderate POAG who received a
Schlemm canal microstent combined with phacoemulsification compared with
phacoemulsification alone.
PMID- 29945800
TI - Baseline Lamina Cribrosa Curvature and Subsequent Visual Field Progression Rate
in Primary Open-Angle Glaucoma.
AB - PURPOSE: To investigate the relationship between the degree of posterior bowing
of the lamina cribrosa (LC) at baseline and the rate of subsequent visual field
(VF) progression in eyes with primary open-angle glaucoma (POAG). DESIGN:
Prospective, observational study. PARTICIPANTS: One hundred one early-stage (VF
mean deviation [MD], -5.0 to -0.01 dB) POAG eyes that met the following
conditions: (1) follow-up longer than 3.5 years, (2) more than 5 reliable
standard automated perimetry tests, and (3) medically well-controlled intraocular
pressure during follow-up. METHODS: All participants underwent swept-source OCT
scanning of the LC at baseline. The area enclosed by a vertical line at the
anterior laminar insertion, anterior LC plane, and reference plane of Bruch's
membrane opening (BMO) was divided by D (distance between the 2 cross-points made
by vertical lines drawn from the anterior laminar insertion to the reference
plane of BMO) to approximate the LC depth (LCD). The difference between the LCD
and mean anterior laminar insertion depth was defined as the LC curvature index
(LCCI). To consider the steepness of the LC curve, the adjusted LCCI (aLCCI) was
calculated as LCCI divided by D and multiplied by 100. The mean LCD (mLCD), mean
LCCI (mLCCI), and mean aLCCI (maLCCI) were computed by averaging the measurements
on 12 radial scans. The subsequent MD slope and associated factors were analyzed.
MAIN OUTCOME MEASURES: Lamina cribrosa parameters and subsequent MD slope.
RESULTS: The participants' mean baseline MD was -3.8 +/- 3.4 dB. The mean
baseline mLCD, mLCCI, and maLCCI were 419.0 +/- 111.2 MUm, 76.4 +/- 29.0 MUm, and
4.8 +/- 1.9, respectively. A greater MD slope was associated with a greater
baseline maLCCI (P < 0.001). We found a statistically significant breakpoint for
the maLCCI (4.12) above which a larger maLCCI showed a steeper MD slope (P <
0.001). Analysis by age revealed that significantly more VF progression with
maLCCI changes occurred in the relatively younger group (<=69 years; P = 0.043).
CONCLUSIONS: The baseline maLCCI showed a significant correlation with the rate
of subsequent VF deterioration. This suggests that, in POAG eyes with greater
posterior bowing of the LC, the axons of retinal ganglion cells may be more
vulnerable to further glaucomatous injury.
PMID- 29945801
TI - Descemet Endothelial Thickness Comparison Trial: A Randomized Trial Comparing
Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet
Membrane Endothelial Keratoplasty.
AB - PURPOSE: To compare clinical outcomes of ultrathin Descemet stripping automated
endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial
keratoplasty (DMEK) in the treatment of corneal endothelial dysfunction. DESIGN:
Patient and outcome-masked, randomized controlled clinical trial. PARTICIPANTS:
Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or
pseudophakic bullous keratopathy who were considered good candidates for DMEK or
UT-DSAEK. METHODS: Study eyes were randomized by the eye bank to UT-DSAEK or DMEK
1 to 2 days before surgery. MAIN OUTCOME MEASURES: The primary outcome of the
trial was best spectacle-corrected visual acuity (BSCVA) at 6 months. Secondary
outcomes included 3- and 12-month BSCVA; 3-, 6-, and 12-month endothelial cell
counts; intraoperative and postoperative complications; and change in pachymetry.
RESULTS: A total of 216 patients with endothelial dysfunction were screened, and
50 eyes of 38 patients were enrolled by 2 surgeons at Casey Eye Institute at
Oregon Health & Science University in Portland, Oregon, and at Byers Eye
Institute at Stanford University in Palo Alto, California. Overall, we found DMEK
to have better visual acuity outcomes compared with UT-DSAEK after correcting for
baseline visual acuity: compared with UT-DSAEK, those randomized to DMEK had 1.5
lines better BSCVA at 3 months (95% confidence interval [CI], 2.5-0.6 lines
better; P = 0.002), 1.8 lines better BSCVA at 6 months (95% CI, 2.8-1.0 lines
better; P < 0.001), and 1.4 lines better BSCVA at 12 months (95% CI, 2.2-0.7
lines better; P < 0.001). Average endothelial cell counts were 1963 cells/mm2 in
DMEK and 2113 cells/mm2 in UT-DSAEK at 6 months (P = 0.17) and 1855 cells/mm2 in
DMEK and 2070 cells/mm2 in UT-DSAEK at 12 months (P = 0.051). Intraoperative and
postoperative complication rates were similar between groups. CONCLUSIONS:
Descemet membrane endothelial keratoplasty had superior visual acuity results
compared with UT-DSAEK at 3, 6, and 12 months in patients with isolated
endothelial dysfunction with similar complication rates.
PMID- 29945802
TI - Implications and attitudes of audiologists towards smartphone integration in
hearing healthcare.
AB - : In a relatively short period of time, modern societies have been transformed by
the ubiquitous uptake of advanced and portable mobile communication, computation,
and sensors available on smartphones. Looking forward, it is anticipated that
smartphones will have an increasingly important role in health management
including the delivery of hearing healthcare and operation of hearing
instruments. OBJECTIVE: This paper provides a brief overview of the role of
smartphones in audiologic rehabilitation and hearing research and reports on the
findings of a survey assessing attitudes of audiologists towards smartphone
integration in hearing healthcare. DESIGN: A total of 258 audiologists working in
the United States completed the 10-item survey. RESULTS: The key finding from the
survey is that practitioners generally expressed a high willingness to integrate
smartphone technology in patient care. Counterintuitively, it was observed that
clinicians with the least number of years of experience had relatively more
negative attitudes toward smartphone integration in hearing healthcare than
clinicians with comparatively more years of experience. CONCLUSIONS: The findings
suggest that the attitudes of audiologists likely do not represent a barrier
regarding smartphone integration in audiologic rehabilitation.
PMID- 29945803
TI - Microenvironmental support for cell delivery to the inner ear.
AB - Transplantation of mesenchymal stromal cells (MSC) presents a promising approach
not only for the replacement of lost or degenerated cells in diseased organs but
also for local drug delivery. It can potentially be used to enhance the safety
and efficacy of inner ear surgeries such as cochlear implantation. Options for
enhancing the effects of MSC therapy include modulating cell behaviour with
customized bio-matrixes or modulating their behaviour by ex vivo transfection of
the cells with a variety of genes. In this study, we demonstrate that MSC
delivered to the inner ear of guinea pigs or to decellularized cochleae
preferentially bind to areas of high heparin concentration. This presents an
opportunity for modulating cell behaviour ex vivo. We evaluated the effect of
carboxymethylglucose sulfate (Cacicol(r)), a heparan sulfate analogue on spiral
ganglion cells and MSC and demonstrated support of neuronal survival and support
of stem cell proliferation.
PMID- 29945804
TI - Intracochlear pressure in response to high intensity, low frequency sounds in
chinchilla.
AB - Exposure to high intensity (blast) sounds can result in both conductive and
sensorineural damage to hearing. This includes rupture of the tympanic membrane
and dislocation of the middle ear ossicles, as well as damage to the inner and
outer hair cells in the cochlea. A clearer understanding of how the hearing
system responds to blast could help us better prevent auditory trauma, and
support those who have been exposed to such sounds. Chinchillas are often used in
studies of hearing due to the similarity between the chinchilla and human
audiograms. The suitability of their use in research on auditory trauma from
blast noise will depend on the extent to which cochlear pressures generated in
chinchillas compare to those in humans. In order to gain a more detailed
understanding of the response of the ear to high intensity sounds, a custom built
sound concentrating horn was used to expose chinchilla cadaveric ears to a series
of single frequency tones between 10 and 1280 Hz, with varying intensities from
90 to 194 dB SPL while intracochlear pressures were measured simultaneously in
the scala vestibuli and scala tympani. These results were then compared to
similar, previously published data from human cadavers. In both human and
chinchillas, intracochlear pressures increased with applied sound pressure up to
about 120 dB SPL, but began to saturate at higher intensities. The exact
saturation point and the saturation pressures showed a strong frequency
dependence. Intracochlear pressure magnitudes in chinchillas show some
similarities with those measured in humans, but also significant differences,
particularly at very high intensity levels such as those found in a blast. These
differences should be taken into account when conducting blast studies in
chinchillas.
PMID- 29945805
TI - Unattended versus attended blood pressure measurement: Mean values and
determinants of the difference.
PMID- 29945806
TI - Prevalence, long-term prognosis and medical alternatives for patients admitted
for acute coronary syndromes and prasugrel contraindication.
AB - BACKGROUND: Prasugrel is a potent antiplatelet therapy that has demonstrated to
be superior to clopidogrel for patients with acute coronary syndromes (ACS) but
has three main contraindications. METHODS: Prospective study of all patients
admitted for ACS in two hospitals. Prasugrel contraindication group was defined
by the presence of age >75 years, weight <60 kg or previous stroke. We also
performed a propensity score matching to obtain a well-balanced subset of
patients with the same probability of receiving ticagrelor. RESULTS: We included
8207 patients and 2538 (30.9%) had any contraindication for prasugrel, being age
>75 years the most frequent (29.0%). Hospital mortality was 4.4% and it was >2
fold higher in patients with any contraindication for prasugrel (7.9% vs. 2.8%; p
< 0.01). Postdischarge follow-up (median 59.9 months) revealed that patients with
prasugrel contraindication had higher cardiovascular and all-cause mortality as
well as a first major cardiovascular event (MACE). No differences in bleeding
rates were found in patients with vs. without prasugrel contraindication.
Prasugrel contraindication was independently associated to higher cardiovascular
(HR: 1.42) and all-cause mortality (HR: 1.47), as well as higher MACE (HR: 1.25).
In the sub-cohort of 482 pairs of patients, obtained by a propensity score
matching, ticagrelor treatment was associated with lower cardiovascular death
(HR: 0.22), all-cause mortality (HR: 0.30) and first MACE (HR: 0.58) in patients
with prasugrel contraindication. CONCLUSIONS: Almost one third of ACS patients
have prasugrel contraindications and they have worst in in-hospital and post
discharge prognosis. Ticagrelor improved postdischarge outcomes in patients with
prasugrel contraindications.
PMID- 29945807
TI - Long-term follow-up and clinical implications in Chinese patients with aortic
intramural hematomas.
AB - BACKGROUND: Intramural hematomas (IMHs) are reported to dynamically evolve into
different clinical outcomes ranging from regression to aortic rupture, but no
practice guidelines are available in China. OBJECTIVE: To determine the evolution
of IMHs after long-term follow-up and to identify the predictive factors of IMH
outcomes in the Chinese population. METHODS: A total of 123 IMH patients with
clinical and imaging follow-up data were retrospectively studied. The primary
endpoints were aortic disease-related death, aortic dissection, penetrating
aortic ulcer (PAU), thickening of the aortic hematoma and aortic complications
requiring surgical or endovascular treatment. RESULTS: All 123 IMH patients were
monitored clinically. The follow-up duration ranged from 1.4 to 107 months
(median, 20 months). Thirty-nine patients had type A IMH, and 84 had type B. The
multivariate analysis showed that a baseline MAD >= 44.75 mm (2.9% vs 61.4%, P <
0.001) and acute PAUs (2.9% vs 34.1%, P = 0.008) were independent predictors of
aorta-related events. CONCLUSIONS: Medication and short-term imaging are
recommended for Chinese IMH patients with a hematoma thickness < 10.45 mm and a
baseline MAD < 44.75 mm. Rigorous medical observation should also be performed
during the acute phase of IMH.
PMID- 29945808
TI - Incidence of thromboembolic events following atrial fibrillation catheter
ablation and rate control strategies according to the kind of oral
anticoagulation: A systematic review and meta-analysis.
AB - INTRODUCTION: Anticoagulantion therapy (OAT) represents the cornerstone to reduce
thromboembolic events for atrial fibrillation (AF). Recent studies suggest that
AF catheter ablation on top of OAT may be useful to further reduce the
thromboembolic risk in AF patients. The aim of the present study is to compare
the long-term risk of thromboembolic events and treatment-related complications
in patients with AF treated by OAT strategies and catheter ablation. METHODS:
Pubmed, Cochrane and Google Scholar were searched for studies including >500
patients evaluating AF patients treated with OAT (VKA: vitamin K antagonist or
DOAC: Direct oral anticoagulants) and/or AF ablation. Pooled incidence of
stroke/year was the primary end point, while that of stroke, of all cause
bleeding and of major bleeding the secondary ones. All the analyses were
stratified according to the CHADS2 score of included patients. RESULTS: Overall,
27 studies were selected, including 50,973 patients in the AF catheter ablation
group; 281,595 patients in the VKA group; 54,811 patients in the DOAC group.
After a mean follow-up of 2.4 (1.5-3.8) years, the overall incidence of stroke
and thromboembolic events was 0.63 per 100 patients/year in AF ablation group,
2.09 per 100 patients/year in VKA group and 1.24 per 100 patients/year in DOAC
group (p < 0.001). After stratification in 4 groups according to CHADS2 score,
the incidence of thromboembolic events remained lower in patients included in the
AF ablation, followed by DOAC and VKA respectively (p < 0.001), for each CHADS2
cluster. Both the incidence of all cause bleedings and major bleedings resulted
lower in AF ablation group (p < 0.001). The incidence of all-cause mortality in
the AF ablation group was significant lower than in the group of OAT (p <
0.0001). CONCLUSION: AF catheter ablation significantly reduces the incidence of
long-term thromboembolic events compared to both VKA and DOAC. This reduction is
maintained in all CHADS2 score clusters and is strengthened by the concomitant
reduction in hemorrhagic complications provided by AF ablation.
PMID- 29945809
TI - [Osteochondroplastic tracheobronchopathy: About three cases].
AB - INTRODUCTION: Osteochondroplastic tracheobronchopathy (OCTB) is a rare disorder
of unknown cause that affects the tracheobronchial tree. It is characterized by
multiple cartilaginous formations or bone nodules projecting into the tracheal or
proximal bronchial lumen. It is usually asymptomatic because of the slow
progression of the nodules. However, chronic cough, recurrent hemoptysis or
recurrent respiratory infections have been reported. OBSERVATIONS: We describe
the cases of three patients with symptomatic OCTB: two men and one woman
consulting for bronchial infections or pneumonia with sputum difficulties (2
cases) or simply for chronic cough (1 case). In all three cases, the diagnosis
was suspected because of irregularities of the tracheal or bronchial wall with
calcification seen on imaging and confirmed at bronchoscopy with biopsy
specimens. No specific therapy was initiated in these patients except for the
treatment of associated complications or comorbidities. CONCLUSION: OCTB is a
benign pathology which can lead to bronchial symptoms ranging from mild cough to
severe airway obstruction due to tracheobronchial stenosis. A key to diagnosis,
limiting non-essential examinations and biopsies, is to consider OCTB based on CT
scan or bronchoscopy based on irregularities of the tracheal or bronchial wall
with calcification.
PMID- 29945810
TI - [Smoking and vaping in France].
AB - INTRODUCTION: The aim of the article is to present a summary of current knowledge
on tobacco smoking in France available through representative population surveys.
STATE OF ART: Smoking is very common in France as more than a quarter (28.7%) of
15-75years old individuals reported daily smoking in 2016. The rate is also high
among 15-year-old (14.6%) and half of them (51.8%) have already smoked one
cigarette. Since the 1970s, sex differences in smoking behaviour are narrowing.
More recently, since 2000, smoking prevalence has tended to decrease among the
most advantaged individuals but to increase among less advantaged ones. These
social inequalities, which are becoming more and more pronounced, are being
observed from smoking initiation, often before the age of 18. Daily users of E
cigarettes represent 2.5% of individuals from 15-75 years in France. They are
also tobacco smokers (58.8%) or former smokers (41.2%). PERSPECTIVES: Taking
social inequalities in health into consideration, notably regarding smoking
initiation, is a key challenge in the fight against smoking. CONCLUSIONS: It is
essential to strengthen efforts to decrease the rate of smoking in France. The
2017 Health Barometer and Escapad surveys will allow evaluation of the public
policies implemented in 2016 and determine whether they have had an impact on the
image of smoking and on smoking rates.
PMID- 29945811
TI - [Evaluation of cardiac MRI in the follow up assessment of patients with pulmonary
arterial hypertension].
AB - Haemodynamic follow up in pulmonary arterial hypertension (PAH) is currently
based on right heart catheterisation (RHC). The primary objective of the EVITA
study is to compare the use of cardiac magnetic resonance imaging (cMRI) with RHC
in the identification of an unfavourable hemodynamic status. The secondary
objectives are to determine the role of cMRI in the follow up process. Patients
will undergo at diagnosis and at follow up visits both RHC and cMRI. Patients
will be followed and treated according to the current guidelines. The primary
endpoint will be an unfavourable haemodynamic status defined by cardiac
index<2.5L/min/m2 or a right atrial pressure>=8mm Hg measured with RHC compared
with a cardiac index<2.5L/min/m2 or right ventricle ejection fraction<35% or an
absolute decrease of 10% from the previous measurement with cMRI. Exact values of
sensitivity, specificity and 95% confidence intervals will be computed. A
population of 180 subjects will have a power of 90% with an alpha risk of 5%.
Univariate and multivariate Cox analysis will allow answering to the secondary
objectives. We expect to demonstrate that cMRI could be partly used instead of
RHC in the follow up of patients with PAH.
PMID- 29945812
TI - [Pathophysiology of right ventricular hemodynamics].
AB - The right ventricle (RV) plays a key role in the maintenance of an adequate
cardiac output whatever the demand, and thus contributes to the optimization of
the ventilation/perfusion ratio. The RV has a thin wall and it buffers the
physiological increases in systemic venous return without causing a deleterious
rise in right atrial pressure (RAP). The RV is coupled to the pulmonary
circulation which is a low pressure, low resistance, high compliance system. In
the healthy subject at rest, the contribution of the RV to right heart systolic
function is surpassed by the contribution of both left ventricular contraction
and the respiratory pump. RV systolic function plays a contributory role during
exercise and in patients with pulmonary hypertension. The RV compensates better
for volume overload than for pressure overload and is more capable of sustaining
chronic increases in load than acute ones. An impaired RV-pulmonary artery
coupling leads to a major mismatch between RV function and arterial load
("afterload mismatch") and is associated progressively with a low cardiac output
and a high RAP. Right ventricular dysfunction is involved in the pathophysiology
of both cardiovascular and pulmonary diseases, and may partly explain the
deleterious haemodynamic consequences of mechanical ventilation.
PMID- 29945813
TI - Can natural killer cells represent an early life immune response in development
of allergic asthma? More precise data analysis should be considered.
PMID- 29945814
TI - Reply.
PMID- 29945815
TI - Natural course of new-onset urticaria: Results of a 10-year follow-up,
nationwide, population-based study.
AB - BACKGROUND: Previous epidemiologic studies of the natural course of urticaria
mainly focused on chronic spontaneous urticaria and were conducted at hospitals.
The natural course of new-onset urticaria in the general population is unknown.
METHODS: Patients with new-onset urticaria were identified from the National
Health Insurance Service-National Sample Cohort data. Patients who had at least
one visit for urticaria in 2002 and 2003 were excluded and the study cohort
consisted of 1,027,620 subjects with no history of urticaria. We analyzed
cumulative incidences of urticaria, chronic urticaria, and chronic urticaria
remission using the life table estimation method from 2004 to 2013. Their
association with related factors was analyzed using the Cox proportional hazards
analysis. RESULTS: From 2004 to 2013, a total of 49,129 patients with new-onset
urticaria were identified. The 10-year cumulative incidence rate of urticaria for
the general population was 4.9% and that of chronic urticaria among patients with
new-onset urticaria was 7.8%. Remission rates of chronic urticaria were 52.6% at
1 year and 88.9% at 5 years. Age, sex, residential area, and autoimmune thyroid
disease were significantly associated with urticaria or chronic urticaria, but
not with chronic urticaria remission, after adjusting for covariates. Female
individuals were more likely to have new-onset urticaria but less likely to
develop chronic urticaria compared with male individuals. CONCLUSIONS: During the
10-year follow-up period, only a small proportion of patients with new-onset
urticaria developed chronic urticaria. Remission was achieved in the majority of
patients with chronic urticaria regardless of demographic characteristics or
accompanying thyroid disease.
PMID- 29945817
TI - Pulmonary Embolism Among Patients With Acute Exacerbation Of Chronic Obstructive
Pulmonary Disease: Implications For Emergency Medicine.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of
morbidity and mortality worldwide. Common in COPD are acute exacerbations (AE
COPD) that cause acute dyspnea, cough, and bronchospasm. Symptoms of AE-COPD
mimic pulmonary embolism (PE). METHODS: We conducted a systematic review of the
literature to assess the prevalence of PE in patients admitted to the hospital
with a clinical diagnosis of AE-COPD. Following the Preferred Reporting Items for
Systematic Reviews and Meta-Analysis guidelines, we queried PubMed and MEDLINE
databases from 1990 to 2017. The search term "prevalence pulmonary embolism,
COPD" was used, and Boolean operators were used to combine search terms. Data
were extracted from each article, specifically the sample size, study setting,
design, and the prevalence of PE. RESULTS: A total of 5 articles were included
that demonstrated a prevalence of PE among patients with a clinical diagnosis of
AE-COPD that ranged from 3.3-29.1%. Sample sizes varied from 49-197 patients.
Studies occurred in both emergency department and inpatient settings, including
intensive care units. Among the studies that reported patient characteristics
associated with PE in AE-COPD, both obesity and immobility were important.
CONCLUSION: Studies reporting the prevalence of PE during AE-COPD vary
considerably in their methods and results. Because of the relatively high
prevalence of PE during AE-COPD, it is important for providers to be aware of
this linkage between the 2 conditions and to screen patients using clinical
gestalt and validated screening tools until more emergency department data are
available.
PMID- 29945816
TI - Analysis of the relevance between molecular subtypes and efficacy of neoadjuvant
chemotherapy in breast cancer as well as its prognostic factors.
AB - BACKGROUND: Accurate pathological assessment of breast specimens after NACT is
crucial. It is beneficial to determine the treatment efficacy and predict
prognosis. So we should explore the relevance between molecular subtypes and
efficacy of neoadjuvant chemotherapy in breast cancer as well as its prognostic
factors, which about survival analysis and disease free survival involved, which
was one part of contributing for evaluating in terms of global survival and
disease free survival. METHODS: Medical records of 264 patients with breast
cancer who received neoadjuvant chemotherapy in Breast Center, the Fourth
Hospital of Hebei Medical University, between January 2008 and May 2013. The
relationship between molecular subtypes and neoadjuvant chemotherapy, and
clinical pathological features were analyzed. RESULTS: The total pCR rate was
12.50% (33/264). The rate of pCR were 3.03% (1/33), 9.40% (14/149), 17.39%(8/46),
27.78% (10/36) in Luminal A type, Luminal B type, HER2 overexpression type, and
Triple negative type, respectively. Which was predicted that The pCR rate
associated with breast cancer molecular subtypes (P < 0.05). The pCR rate in
Triple negative type was highest, HER2 overexpression type was showed higher pCR
rate than Luminal A and Luminal B type. Multiple factors analysis results showed
that: the independent impact factors of 5-year overall survival rate in
neoadjuvant chemotherapy breast cancer patients were clinical stage, tumor size,
chemotherapy regimens, lymph node metastasis, estrogen receptor status and
pathological remission; the independent impact factors of 5-year disease free
survival rate were tumor size, chemotherapy regimens, estrogen receptor status,
progesterone receptor status and pathological remission (P < 0.05). Triple
negative type of breast cancer had shorter overall survival and disease-free
survival (P < 0.05). CONCLUSIONS: The pCR was more frequently observed in HER2
overexpression type and Triple negative type of breast cancer. That could achieve
a higher rate of pCR on paclitaxel class joint anthracycline-based chemotherapy.
But Triple negative type showed worse prognosis, due to residual tumor after
neoadjuvant chemotherapy, which could be in combination or sequential, at the
neoadjuvant / adjuvant setting (NCCN 2016 Breast cancer, chemotherapy regimens),
So how to choose a more appropriate neoadjuvant chemotherapy regimens, we should
need further research.
PMID- 29945819
TI - Orofacial cleft management by short-term surgical missions in South America:
literature review.
AB - There is a growing demand for surgical care in South America, particularly for
patients with congenital orofacial clefts (OFCs). Short-term surgical missions
(STSMs) have emerged as a means to deliver surgical expertise and alleviate this
demand. The aim of this study was to review the quantity and quality of peer
reviewed reports on OFC repairs performed by STSMs in South America. A literature
search was conducted using the PubMed, Embase, Web of Science, and SciELO
databases. The search was limited to articles published in English and Spanish.
Descriptive statistics were used for the data analysis. The search yielded 65
studies related to OFCs. Eight (12.3%) were selected for full-text review. Only
five (7.7%) articles met the inclusion criteria. The diverse study designs and
heterogeneous types of data assessment among the selected studies hindered a
comparison between them. This review found a sparse number of publications
pertaining to OFC missions to South America. The articles that were included
demonstrated inconsistencies in reporting patient care data. There is a need for
a more efficient, streamlined method of reporting humanitarian missions for OFC
repairs in order for healthcare professionals to fulfill research and ethical
obligations and offer the best practices in patient-centered care.
PMID- 29945818
TI - 'Agricultural Waste to Treasure' - Biochar and eggshell to impede soil
antibiotics/antibiotic resistant bacteria (genes) from accumulating in Solanum
tuberosum L.
AB - Soil contamination with antibiotics and antibiotic resistant bacteria/genes
(ARB/ARGs) has becoming an emerging environmental problem. Moreover, the mixed
pollutants' transfer and accumulation from soil to tuberous vegetables has posed
a great threat against food security and human health. In this work, the
application of two absorbing materials (maize biochar and sulfate modified
eggshell) was able to reduce the poisonous effect of soil antibiotics on potato
root system by stimulate the dissipation of water-soluble antibiotics in soil;
and also improve food quality by increasing potato starch, protein, fat, and
vitamins. Meanwhile, both amendments could effectively decrease the classes and
the accumulative abundance of ARB and ARGs (sulI, sulII, catI, catII, ermA, ermB)
in the edible parts of potato. The lowest abundance of ARGs was detected in the
biochar application treatment, with the accumulative ARG level of 8.9 * 102 and
7.2 * 102 copies mL-1 in potato peel (sull + catI + ermA) and tuberous root
(sulI), respectively. It is the first study to demonstrate the feasibility of
biochar and eggshell derived from agricultural wastes as green absorbing
materials to reduce soil antibiotic, ARB, and ARGs accumulation risk in tuberous
vegetable.
PMID- 29945820
TI - Family-centred care is acceptable for enhancing nutrition intake in critical care
units.
PMID- 29945822
TI - Presence and degree of residual venous obstruction on serial duplex imaging is
associated with increased risk of recurrence and progression of infrainguinal
lower extremity deep venous thrombosis.
AB - OBJECTIVE: The role of follow-up venous duplex ultrasound (DUS) after acute lower
extremity deep vein thrombosis (DVT) remains unclear, yet it is commonly
performed. We aimed to clarify the role of follow-up DUS. Our primary objective
was to determine the association between the presence of residual venous
obstruction (RVO) on DUS and DVT recurrence or propagation (rDVT). Secondary
objectives included finding risk factors associated with RVO and rDVT. METHODS:
We conducted a retrospective study of patients diagnosed with DVT on DUS from
January 1, 2011, to December 31, 2013, that received a follow-up DUS. Patient
demographics, risk factors, medications, and DUS findings were recorded. Ten
segments from the common femoral to distal calf veins were checked for the
presence of RVO, DVT propagation, and recurrence. RVO was defined as any nonacute
venous obstruction with more than 40% of luminal diameter remaining during
compression or the presence of chronic post-thrombotic occlusive disease. rDVT
was measured as either a new acute DVT in the previously involved segment, or
involvement of a new segment in the same extremity. RESULTS: A total of 185 lower
extremities representing 156 patients met the inclusion criteria. RVO was noted
in 61.1% of limbs. The 3-year rDVT rate was 10.3%. Patients with recurrent venous
thromboembolism or thrombophilia had a higher risk of developing RVO (odds ratio
[OR], 2.89, P < .01; OR, 4.39, P = .04, respectively). Extremities with larger
clot burden had an increased risk of RVO on follow-up DUS (OR, 1.25 per segment;
P < .01). The presence and degree of RVO on follow-up DUS had an increased risk
of rDVT on subsequent DUS (OR, 3.90, P = .04; OR, 1.21 per segment, P = .04,
respectively). Limbs with complete resolution of DVT by DUS had a significantly
decreased risk of rDVT (OR, 0.26; P = .04). CONCLUSIONS: Extremities with larger
initial clot burden exhibited an increased risk of subsequent RVO. The presence
of RVO and, interestingly, the number of involved segments on follow-up DUS
increased the risk of rDVT. Our results suggest that the presence of residual
disease and increased RVO burden on follow-up DUS after an acute DVT may identify
those patients who are at an increased risk for rDVT and may help guide the
duration of anticoagulation therapy.
PMID- 29945821
TI - Bilateral May-Thurner syndrome refractory to iliac aneurysm repair.
AB - Venous complications of iliac artery aneurysms are rare. We report the case of
bilateral iliac aneurysms that resulted in iliac vein outflow obstruction despite
endovascular aneurysm repair. In our patient, bilateral iliac vein stenting
resulted in symptom resolution.
PMID- 29945823
TI - Unraveling the effects of an oxygen shock on cord blood units.
PMID- 29945824
TI - Minimally-invasive Transesophageal Echocardiography for Left Atrial Appendage
Occlusion With a Latest-generation Microprobe. Initial Experience.
PMID- 29945825
TI - Non-motor effects of deep brain stimulation in dystonia: A systematic review.
AB - INTRODUCTION: Deep brain stimulation (DBS) has emerged as an effective treatment
in medically intractable dystonia, with the globus pallidus internus (GPi) being
most frequently targeted. Non-motor symptoms, including pain and psychiatric,
cognitive and sleep disturbances, are increasingly recognized as important
determinants of disease burden in dystonia patients. We reviewed non-motor
outcomes of DBS in dystonia, focusing on GPi-DBS. METHODS: A systematic
literature search of Pubmed and Embase was performed according to the PRISMA
guidelines. RESULTS: Fifty-two studies were included. GPi-DBS reduced pain
related to dystonia. No major effects on anxiety, mood, and cognition were found.
In contrast to motor outcome, non-motor outcome seems more independent of the
etiology of dystonia. However, the impact of potential confounders (e.g. patient
factors, changes in pharmacological treatment) is unclear. CONCLUSION: Despite
the growing interest in non-motor symptoms in dystonia, DBS studies still focus
primarily on motor outcome. We recommend systematic evaluation of both non-motor
and motor features before and after DBS interventions to improve quality of life
and management of patients with dystonia.
PMID- 29945827
TI - Development of apheresis techniques and equipment designed for patients weighing
less than 10 kg.
AB - The procedure of apheresis in pediatric patients, particularly in those with low
weight (body weight<10 kg) presents an important challenge due to particularities
of this group. There are no specific guidelines or enough scientific evidence to
standardize the practice in this group of patients. In addition to the
psychological aspect, the correct calculation of the total blood volume, the
extracorporeal volume of the cell separator and an estimated decrease in
hematocrit must be considered. Personalized protocols for priming of the
apheresis equipment, sufficient blood flow and adequate anticoagulation are
essential for patient comfort and therapeutic success. The purpose of this
article is to present the results of the national study of apheresis practices in
low weight group of children conducted from 2012 to 2018. Protocols and patients'
data collected from various apheresis centers in Argentina were compared with the
apheresis protocols around the world. Our protocols and data were similar to
those in other countries; however, no detailed and specific guidelines for
apheresis practices in this population of patients with unique requirements have
been developed to date.
PMID- 29945828
TI - High risk device registries: Global value, costs, and sustainable funding.
AB - BACKGROUND: Well-designed implant registries have been shown to be a worthwhile
investment, from both a health and economic perspective. However, many registries
do not attain desirable capture rates or lack sufficient funding, potentially
leading to premature termination. This study aims to provide information about
rarely discussed, yet pivotal topics regarding the long-term survival of implant
registries, focusing on costs, funding models, and the role of stakeholders.
METHODS: Worldwide, relatively recently developed breast device (BD) registries
were compared to long-standing, orthopaedic (OD) and cardiovascular device (CD)
registries. A standardised questionnaire was sent to the registries' designated
representatives with key positions, discussing start-up costs, costs of
maintenance, value of investment, governance, stakeholders, funding, and
sustainability. RESULTS: Thirteen registries were included, originating from nine
countries (seven BD registries, five OD registries, one CD registry). In general,
start-up costs were comparable, and younger registries were more expensive to
maintain. Numerous stakeholders showed interest in registry outcomes. However,
only 50% of the registries reported a sustainable funding structure. CONCLUSION:
This study provides a global perspective on implantable device registries. All
registries provided important information, serving three unique purposes by
evaluating the quality of healthcare provided, the quality of all registered
devices, and processing recall information. Yet, only half of the registries were
certain of sustainable funding, and thus their future existence. It is of utmost
importance to bring this to the attention of all parties involved.
PMID- 29945829
TI - Associations of Psychopathic Traits With Local and Global Brain Network Topology
in Young Adult Women.
AB - BACKGROUND: Psychopathic traits vary dimensionally in the population and are
associated with multiple negative outcomes. The impaired integration theory (IIT)
proposes that psychopathic traits are associated with abnormal neural network
topology, such that disturbed integration of neural networks results in a self
perpetuating impairment in rapid integration and learning from multiple
components of information. The IIT is based on findings from male offenders
presenting high scores on all psychopathic traits. The present study investigated
whether IIT predictions of topology abnormalities were associated with
psychopathic traits, measured dimensionally, in young adult women with
subsyndromal scores. METHODS: Seventy-three women, with an average age of 25
years, were assessed using the Psychopathy Checklist-Revised and completed
resting-state magnetic resonance imaging. Preprocessed time series from 90
anatomical regions were extracted to form connectivity matrices and used to
calculate network topology based on graph theory. Correlations between total
psychopathy and factor scores with both the raw connectivity matrix and global
and local graph theory measures were computed. RESULTS: Total psychopathy scores
and behavioral factor scores were related to connectivity between several pairs
of regions, primarily limbic/paralimbic. Psychopathic traits were not associated
with global topology measures. Topology abnormalities, robust across network
formation thresholds, were found in nodes of the default mode network and in hubs
connecting several resting-state networks. CONCLUSIONS: IIT predictions of
abnormal topology of hubs and default mode network nodes with dimensionally
measured psychopathic traits were confirmed in a sample of young women. Regional
abnormalities, accompanied by preserved global topology, may underlie context
specific abnormal information processing and integration.
PMID- 29945830
TI - The influence of sleep and training load on illness in nationally competitive
male Australian Football athletes: A cohort study over one season.
AB - OBJECTIVES: To determine the incidence of illness, and identify the relationship
between sleep, training load and illness in nationally competitive Australian
football athletes. Second, to assess multivariate effect between training load
and/or sleep variables. DESIGN: Cohort study. METHODS: Retrospective analyses of
prospectively collected cohort data were conducted on forty-four male athletes
over a 46-week season. The primary outcome was illness incidence, recorded daily
by medical doctors. Independent variables were acute, chronic and acute:chronic
ratios of: sleep quality, sleep quantity, internal training load and external
training load defined as: total running distance, high speed running distance and
sprint distance. Generalised estimating equations using Poisson (count) models
were fit to examine both univariate and multivariate associations between
independent variables and illness incidence. RESULTS: 67 incidences of illness
were recorded, with an incidence rate of 11 illnesses per 1000 running hours.
Univariate analysis showed acute and chronic sleep hours and quality, as well as
acute sprint and total running distance to be significantly associated with
illness. Multivariate analysis identified that only acute sleep quantity was
significantly, negatively associated with illness incidence (OR 0.49, CI 0.25
0.94) once all univariate significant variables were controlled for. There was no
relationship between external training load and illness when sleep metrics were
controlled for. CONCLUSIONS: In a cohort of Australian football athletes, whose
load was well monitored, reduced sleep quantity was associated with increased
incidence of illness within the next 7 days. Monitoring sleep parameters may
assist in identifying individuals at risk of illness.
PMID- 29945831
TI - The acute effects of exercise on tendon dimensions and vascularity. An
exploratory study using diagnostic ultrasound of the male Achilles tendon.
AB - OBJECTIVES: This study examines the acute morphological changes (up to three
days) in the normal, asymptomatic Achilles tendon (AT) in response to a single
bout of exercise in relation to tendon dimensions and vascularity. DESIGN: Within
subject pre-post design. METHODS: Participants conducted a 7.7km pack march on a
sealed road in a time of 1h 16min (approximately 6kmh-1). The longitudinal image
of the sagittal diameter, transverse image of the area and vascularity at 20mm
proximal to the superior aspect of the calcaneus and longitudinal image of the
sagittal diameter at the insertion was measured the day before the pack march,
immediately afterwards and then three days later. RESULTS: The tendon showed no
significant change in sagittal diameter and cross-sectional area at 20mm proximal
to the calcaneus and at the insertion immediately post-exercise. Tendon
vascularity increased significantly in 91% of the left ATs and 87% of the right
ATs in response to the pack march. Three days after the pack march an increase in
sagittal diameter at the insertion and 20mm proximal to the calcaneus was
observed and increased vascularity was still present in 22% of the ATs.
CONCLUSIONS: This study highlighted the tendon's response to exercise and has
shown that at three days post-exercise that the tendon had not recovered to pre
exercise levels with respect to tendon dimensions and vascularity.
PMID- 29945832
TI - Comparing self-reported physical activity and sedentary time to objective fitness
measures in a military cohort.
AB - OBJECTIVES: Regular vigorous physical activity (PA) and high levels of physical
fitness (PF) confer health benefits. Conversely, sedentary time is a risk factor
for chronic illness, independent of PA. We evaluated associations between self
reported PA, sedentary time, and objective PF measures in military Service
members. DESIGN: Cross-sectional study including 10,105 Air Force Millennium
Cohort participants with a valid physical fitness assessment (PFA). METHODS:
Linear regression assessed associations between self-report PA, screen time, and
usual activity and abdominal circumference (AC) and VO2 max; logistic regression
was used for PFA failure. We stratified by age and sex. RESULTS: Men who self
reported high versus low levels of PA had greater AC (19-29 years: beta=0.23in.,
95% CI 0.07, 0.39; 30-39 years: beta=0.45in., 95% CI 0.17, 0.72). High versus low
self-reported PA was also associated with greater VO2Max (beta=:0.81
1.41mL/kg/min). Self-reported strength training for >=2days/week was associated
with greater VO2Max in 19-29year old men (beta=0.84mL/kg/min, 95% CI 0.09, 0.60)
and 30-39year old women (beta=0.74mL/kg/min, 95% CI 0.02, 1.46). For younger men
and women,<2h of screen time/day was associated with greater VO2Max (Males 19
29years: beta=0.23mL/kg/min, 95% CI 0.44, 1.26; Females 19-29years:
beta=0.83mL/kg/min, 95% CI 0.25, 1.42). PA was not associated with PFA failure,
while screen time was (Males OR: 0.32-0.65, 95% CI 0.17-0.92, p<0.001-0.016).
CONCLUSIONS: Self-reported PA and screen time were associated with some objective
PF measures, including VO2Max and AC. However, screen time alone was associated
with PFA failure.
PMID- 29945833
TI - Rotavirus infection among hospitalized children under five years of age with
acute watery diarrhea in Sri Lanka.
AB - BACKGROUND: Rotavirus is the leading cause of acute watery diarrhoea among
children and is vaccine preventable. The aim of this hospital-based sentinel
surveillance was to study the prevalence, demographic and clinical
characteristics of rotavirus infections and to describe rotavirus genotype
distribution patterns among children under five years of age hospitalized for
acute watery diarrhea during the period of 2009-2016. METHODS: Prospective,
sentinel hospital-based surveillance was conducted in Lady Ridgeway Hospital
(LRH) from 2009 to 2016. Stool samples of children admitted with acute watery
diarrhea were tested by rotavirus antigen detection 'ProSpecT' Enzyme Immunoassay
(EIA) at Department of Virology, Medical Research Institute, Colombo. Specimens
that tested positive for rotavirus were further analyzed at the Regional
Reference Laboratory (RRL) participating in the World Health Organization (WHO)
coordinated Global Rotavirus Surveillance Network (GRSN) to determine the
genotype of strains by reverse-transcriptase polymerase chain reaction. RESULTS:
Of the 6090 children with diarrhea admitted, 1801 (29.5%) had stools taken and
tested. In years with at least 11 months of data (2010 and 2013) rotavirus was
detected in 36.5% (228/624) of specimens. Genotype G1P[8] was the most common
genotype detected throughout the surveillance period (30.1%; 123/408) with G2P
[8], G9P[8] and G3P[8] also detected. CONCLUSIONS: Rotavirus is a common cause of
pediatric diarrhea hospitalizations in Sri Lanka. National introduction of
rotavirus vaccine could reduce the burden of pediatric diarrhea.
PMID- 29945835
TI - A contemporary, 7-year analysis of vascular injury from the war in Afghanistan.
AB - OBJECTIVE: Vascular injury is a leading cause of death and disability in military
and civilian trauma. Although a previous interim study defined the distribution
of vascular injury during the wars in Iraq and Afghanistan, a contemporary
epidemiologic assessment has not been performed. The objective of this study was
to provide a current analysis of vascular injury during the final 7 years of the
war in Afghanistan, including characterization of anatomic injury patterns,
mechanisms of injury, and methods of acute management. METHODS: The Department of
Defense Trauma Registry was analyzed to identify U.S. military service members
who sustained a battle-related vascular injury and survived to be treated at a
surgical facility in Afghanistan between January 1, 2009, and December 31, 2015.
All battle-related injuries (nonreturn to duty) were used as a denominator to
establish the injury rate. Mechanism and anatomic distribution of injury as well
as the acute management strategies of revascularization, ligation, and use of
endovascular techniques were defined. RESULTS: Of 3900 service members who
sustained a battle-related injury, 685 patients (17.6%) had 1105 vascular
injuries (1.6 vascular injuries per patient). Extremity trauma accounted for 72%
(n = 796) of vascular injuries, followed by the torso (17%; n = 188) and cervical
(11%; n = 118) regions. Lower extremity vascular injury was the most prevalent
anatomic location (45%; 501/1105). Explosion with fragment penetration accounted
for 70% (477/685) of injuries, whereas gunshot wounds accounted for 30%
(205/685). Open repair was performed in 559 cases (57%; 554/981), whereas
ligation was the initial management strategy in 40% (395/981) of cases. In
addition, 374 diagnostic endovascular procedures were completed, 27 therapeutic
endovascular interventions to include stent placement and angioplasty were
performed and 55 inferior vena cava filters were placed. Mortality of the
vascular injury cohort was 5%. CONCLUSIONS: The rate of vascular injury in modern
combat is higher than that reported in previous wars. Open reconstruction is
performed in half of cases, although ligation is an important damage control
option, especially for minor or distal vessel injuries. Angiographic techniques
are increasingly being used and documented within wartime registries more than
ever. Proficiency with open and endovascular methods of vascular injury
management remains a critical need for the U.S. military and will require
partnership with civilian institutions to attain and maintain.
PMID- 29945834
TI - Tailoring immunisation programmes: Using behavioural insights to identify
barriers and enablers to childhood immunisations in a Jewish community in London,
UK.
AB - INTRODUCTION: Due to regular vaccine preventable disease outbreaks and sub
optimal immunisation uptake in the London borough of Hackney, home to the largest
Charedi Orthodox Jewish community in Europe, it was decided, in consultation with
the community, to implement the WHO Tailoring Immunization Programmes approach
(TIP). DESIGN: The WHO Tailoring Immunization Programmes (TIP) approach was used.
TIP provides a framework based on behavioural insights methodology to identify
populations susceptible to vaccine preventable diseases, diagnose supply and
demand side barriers and enablers to vaccination and recommend evidence-informed
responses to improve vaccination coverage. RESULTS: The results of the formative
research and behavioural analysis challenged the assumption that a cultural or
religious anti-vaccination sentiment existed within the community. Critical
issues related to access to and convenience of immunisation services. Service
providers in the area have challenges due to having to deliver immunisation
services to the large numbers of children without additional resource. Where
mothers were choosing to delay or refuse vaccinations their reasons were broadly
similar to the wider population. The behavioural analysis identified potential
categorisation of subgroups within the community enabling a more tailored
approach to addressing concerns and meeting parents' needs. CONCLUSION: The TIP
approach was an effective way of investigating factors linked to sub-optimal
immunisation within the Charedi community. The use of behavioural insights
enabled the categorisation of subgroups so that more targeted interventions could
be developed. The comprehensive stakeholder engagement which is a key pillar of
the TIP approach ensured a deeper understanding of the barriers and enablers to
vaccination as well as increasing the level of ownership in the community. TIP
should be considered as a useful approach to identify main facilitators and
barriers to vaccination in communities with suboptimal immunisation uptake.
PMID- 29945836
TI - Risk factors for perioperative mortality after revascularization for acute aortic
occlusion.
AB - OBJECTIVE: Acute aortic occlusion (AAO) is a life-threatening event necessitating
prompt revascularization to the pelvis and lower extremities. Because of its
uncommon nature, outcomes after revascularization for AAO are not well
characterized. Our aim was to describe the perioperative morbidity and mortality
associated with revascularization and to identify the patients at highest risk.
METHODS: A retrospective chart review was performed of patients who presented to
our institution from 2006 to 2017 with acute distal aortic occlusion. Patients
with a prior aortofemoral bypass were excluded, but those with aortoiliac stents
were included. Baseline demographics and comorbidities, preoperative clinical
presentation and imaging, procedural details, and postoperative hospital course
were reviewed. The primary outcome was 30-day mortality, and major complications
were evaluated as secondary outcomes. Logistic regression models were constructed
to identify factors associated with 30-day mortality. RESULTS: We identified 65
patients who underwent revascularization for AAO. Median age was 63 years (range,
35-89 years), and 64.6% were male; 56.4% of patients presented within 24 hours of
symptom onset, and 43.8% were treated within 6 hours of presentation. There were
particularly high rates of prior coronary artery disease (62.3%) and chronic
obstructive pulmonary disease (41.0%); 18.5% had prior iliac stents. Preoperative
imaging in 44 patients showed occlusion of the inferior mesenteric artery in
36.0% and both internal iliac arteries in 34.7%. Treatments for revascularization
included axillobifemoral bypass (55.4%), aortoiliac thromboembolectomy (15.4%),
aortobifemoral bypass (13.9%), and aortoiliac stenting (15.4%). Overall 30-day
mortality was 27.7% and was not affected by treatment modality. Mortality was
highest in patients older than 60 years (40.5% vs 10.7%; P = .01) and those
presenting with lactate elevation (45.5% vs 5.9%; P = .004) or motor deficit in
at least one extremity (36.6% vs 9.5%; P = .03). Univariate predictors of 30-day
mortality were age >=60 years (odds ratio [OR], 5.68; 95% confidence interval
[CI], 1.45-22.26; P = .01), presentation with motor deficit (OR, 5.48; 95% CI,
1.12-26.86; P = .04), presentation with elevated lactate level (OR, 13.33; 95%
CI, 1.58-11.57; P = .02), history of prior stroke (OR, 4.80; 95% CI, 1.21-18.97;
P = .03), and bilateral internal iliac artery occlusion (OR, 7.11; 95% CI, 1.54
32.91; P = .01). At least one postoperative complication was observed in 78.5% of
patients, including acute kidney injury (56.9%, with 21.5% requiring
hemodialysis), respiratory complications (46.2%), cardiovascular complications
(33.9%), major amputation (15.4%, bilateral in 7.7%), and bowel ischemia (10.8%).
CONCLUSIONS: Even with prompt revascularization and despite the chosen treatment
modality, AAO carries high risk of mortality and numerous life-threatening
complications. Older patients presenting with elevated lactate levels, motor
deficit, and bilateral internal iliac artery occlusions are at the highest risk
of perioperative mortality. These factors may aid in risk stratification and
managing expectations in this critically ill population.
PMID- 29945837
TI - Safety and durability of infrarenal aorta as distal landing zone in fenestrated
or branched endograft repair for thoracoabdominal aneurysm.
AB - OBJECTIVE: Manufacturers often recommend the iliac arteries as the distal landing
zone in fenestrated or branched endovascular aortic repair (FB-EVAR) for
thoracoabdominal aneurysm. It is not uncommon to choose distal landing at the
infrarenal aorta for preservation of lumbar arteries or the inferior mesenteric
artery (IMA); however, the safety and durability of this procedure have not been
verified in the literature. METHODS: Consecutive patients who underwent FB-EVAR
with distal landing at the infrarenal aorta were reviewed retrospectively. The
primary outcome measured any type IB endoleak over time. Secondary outcomes
measured perioperative complications of paraplegia and bowel ischemia,
preservation of lumbar artery and IMA, and degeneration of infrarenal aorta
(diameter of infrarenal aorta at landing zone) and common iliac arteries (maximum
diameters) over time. RESULTS: Between August 2011 and August 2017, 40 patients
(40% male with a mean age of 72 +/- 8 years) affected by types I (37.5%), II
(25.0%), III (20.0%), and V (17.5%) thoracoabdominal aneurysms were included. The
mean aneurysm diameter was 6.4 +/- 1.5 cm. There was no immediate or delayed type
IB endoleak with mean follow-up period of 15 +/- 18 months (range, 0-72 months).
Postoperative complications included six (15%) spinal cord ischemia (five
temporary and one permanent) and no mesenteric ischemia. There were three deaths
(7.5%) within 30 days. Follow-up with computed tomography arteriography showed
that 37 patients (92.5%) had at least one lumbar artery preserved. Out of the 31
preoperatively patent IMA, 23 (74.2%) were preserved. There was one incidental
finding of new focal dissection distal to the stent graft end. Mean infrarenal
aorta diameters were 24.8, 27.7, 27.7, and 29.4 mm immediately preoperatively,
and at 1 and 2 years postoperatively, respectively. The mean maximal right common
iliac diameters were stable and measured 15.8, 15.9, and 14.8 mm preoperatively,
immediately postoperatively, and 1 year postoperatively, respectively. Mean
maximal left common iliac diameters were also stable and measured 15.7, 15.9, and
14.7 mm preoperatively, immediately postoperatively, and at 1 year
postoperatively, respectively. CONCLUSIONS: Our early experience showed that
distal landing at the infrarenal aorta was secure in FB-EVAR with no type IB
endoleak, although the observation of gradual infrarenal aortic degeneration
mandates regular surveillance.
PMID- 29945838
TI - Patients with end-stage renal disease have poor outcomes after endovascular
abdominal aortic aneurysm repair.
AB - OBJECTIVE: Although endovascular repair of abdominal aortic aneurysms (AAAs) has
been demonstrated to have favorable outcomes, not all cohorts of patients with
AAA fare equally well. Our goal was to investigate perioperative and 1-year
outcomes in patients with end-stage renal disease (ESRD) on dialysis, who have
traditionally fared worse after vascular interventions, to assess how ESRD
affects outcomes in a large modern cohort of endovascular aneurysm repair (EVAR)
patients. METHODS: The Vascular Quality Initiative database was queried for all
patients undergoing EVAR from 2010 to 2017. ESRD patients were compared with
patients not on dialysis. Propensity-matched scoring and multivariable analysis
were used to isolate the effects of ESRD. RESULTS: Of 28,683 EVARs identified,
there were 321 (1.12%) patients with ESRD on dialysis. Patients with ESRD had no
difference in presenting AAA size (57.5 +/- 12.7 mm vs 56.7 +/- 17.2 mm; P =
.44); however, they had more urgent/emergent repairs (20.6% vs 13.6%; P = .002)
than those without ESRD. ESRD patients were more often younger, nonwhite, and
nonobese and less likely to have commercial insurance (P < .05). ESRD patients
more often had hypertension, coronary artery disease, congestive heart failure,
previous lower extremity bypass, aneurysm repair, and carotid interventions (P <
.05). There was no difference in the rate of concomitant procedures. Matching
based on demographics, comorbidities, and operative details showed that ESRD
patients had longer hospital length of stay (4.8 +/- 9.4 days vs 4.1 +/- 12.6
days; P = .026) and higher 30-day mortality (7% vs 2.4%; P < .001). There was no
difference in cardiac, pulmonary, lower extremity, bowel, and stroke
complications or return to the operating room. On multivariable analysis, ESRD
was associated with 30-day mortality (odds ratio, 4.1; 95% confidence interval,
2.6-6.7; P < .001). Of the 24,750 elective EVARs, 1.04% had ESRD on dialysis.
Matched data for elective EVAR show increased postoperative length of stay,
hospital mortality, and 30-day mortality for ESRD patients on dialysis compared
with those who are not. There was no association with postoperative myocardial
infarction or pulmonary complications. At 1 year, patients with ESRD on dialysis
had worse survival (78% vs 94%; P < .001), and ESRD was associated with higher
mortality (hazard ratio, 3.3; 95% confidence interval, 2.5-4.2; P < .001).
CONCLUSIONS: Among patients undergoing EVAR, ESRD is independently associated
with higher perioperative and 1-year mortality despite not being associated with
higher postoperative complications. This should be taken into account during
informed consent for EVAR and risk-benefit considerations in this high-risk
population, particularly for elective repair.
PMID- 29945839
TI - Cerebrovascular injuries found in acute type B aortic dissections are associated
with blood pressure derangements and poor outcome.
AB - OBJECTIVE: Cerebrovascular injury (CVI) is a recognized but underappreciated
complication of acute type B aortic dissection (ATBAD). This study was performed
to determine risk factors for CVI associated with ATBAD and, in particular, the
possible contributory role of aggressive anti-impulse therapy. METHODS: A
retrospective review of all patients presenting to a tertiary medical center with
an ATBAD between January 2003 and October 2012 was conducted. All CVIs were
adjudicated by a vascular neurologist and assigned a probable cause. The initial
intensity of anti-impulse therapy was defined as the difference in mean arterial
pressure (DeltaMAP) from presentation to subsequent admission to the intensive
care unit. RESULTS: A total of 112 patients were identified. The average age was
61 years; 64% were male, and 59% were African American. Twenty patients required
operative intervention (14 thoracic endovascular aortic repairs and 6 open). CVI
occurred in 13 patients (11.6%): 9 were hypoperfusion related (6 diffuse hypoxic
brain injuries and 3 watershed infarcts), 2 were procedure related (both thoracic
endovascular aortic repairs), 1 was an intracranial hemorrhage on presentation,
and 1 was a probable embolic stroke on presentation. CVI patients had
demographics and comorbidities comparable to those of the non-CVI patients. CVI
was associated with operative intervention (54% vs 13%; P = .002). Thirty-day
mortality was significantly higher in CVI patients (54% vs 6%; P < .001).
Patients who suffered a hypoperfusion brain injury had a higher MAP on
presentation to the emergency department (142 mm Hg vs 120 mm Hg; P = .034) and a
significantly greater reduction in MAP (DeltaMAP 49 mm Hg vs 15 mm Hg; P < .001)
by the time they reached the intensive care unit compared with the non-CVI
patients. CONCLUSIONS: In our series, CVI in ATBAD is more frequent than
previously reported and is associated with increased mortality. The most common
causes are related to cerebral hypoperfusion. Higher MAP on presentation and
greater decline in MAP are associated risk factors for hypoperfusion-related CVI.
A less aggressive approach to lowering MAP in ATBAD warrants further study in an
attempt to reduce CVI in ATBAD.
PMID- 29945840
TI - Predicting Clinical Outcome After Surgical Treatment in Patients With Carpal
Tunnel Syndrome.
AB - PURPOSE: Carpal tunnel release (CTR) is typically offered to symptomatic patients
with electrophysiological abnormalities when night orthoses no longer prevent
waking with numbness and preferably before there is any static numbness,
weakness, or atrophy. The ability to predict the amount of symptom relief after
CTR could be beneficial for managing patient expectations and, therefore, improve
treatment satisfaction. Therefore, the aim of this study was to identify
predictors for symptom relief after CTR and to determine their contribution to
symptom relief at 6 months after surgery. METHODS: A total of 1,049 patients who
underwent CTR between 2011 and 2015 at 1 of 11 Xpert Clinics in the Netherlands
were asked to complete online questionnaires at intake and 3 and 6 months after
surgery. Patient demographics, comorbidities, and baseline scores were considered
potential predictors for the amount of symptom relief on the Boston Carpal Tunnel
Questionnaire (BCTQ) score, which was the primary outcome measure. RESULTS: A low
score on the BCTQ at intake, a codiagnosis of a trigger finger, ulnar nerve
neuropathy, trapeziometacarpal joint arthrosis, and instability or arthrosis of
the wrist were associated with a smaller improvement in the BCTQ domains after a
CTR at 6 months after surgery and accounted for 35% to 42% of the variance on the
BCTQ domains in our multivariable regression models. CONCLUSIONS: In this study,
we showed that clinical severity of carpal tunnel syndrome at intake is the most
important factor in estimating symptom relief after surgical treatment.
Furthermore, this study contributes to a more precise understanding of the
capabilities of CTR in relieving symptoms for different subgroups of patients.
Results of our study can be used to manage patient expectation on symptom relief
from CTR. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.
PMID- 29945841
TI - Forces in the Distal Radius During a Pushup or Active Wrist Motions.
AB - PURPOSE: To determine the 6 degrees of freedom forces and moments in the distal
radius that occur during a pushup or other active wrist motions. METHODS: Eight
fresh-frozen cadaveric wrists were moved through 6 physiological motions and held
at 1 static pushup position while the force through the distal radius was
measured with a 6 degrees of freedom load cell. Three levels of compressive force
were applied at the pushup position. RESULTS: Active wrist motions caused axial
forces up to 283 N and moments up to 0.7 N-m. Those motions with a smaller range
had significantly smaller axial forces than the larger flexion-extension or dart
thrower's motions. With an 89-N pushup force applied, the average maximum axial
force was 69 N, the radially directed force was 12 N, and the moment about the
radioulnar axis was 2.3 N-m. Linear extrapolation of the forces to 100% body
weight indicate that the axial force going through the distal radius would be 663
N, the radial force would be 147 N, and the moment about the radioulnar axis
would be 18.6 N-m. CONCLUSIONS: Large distal radius forces and moments can occur
during pushup and active wrist motions. There are not only large axial
compressive forces but also nontrivial radially directed forces. CLINICAL
RELEVANCE: This study may help surgeons and therapists better treat complicated
distal radius fractures as well as provide for better comparisons of existing or
new distal radius plates and constructs that are designed to treat these
complicated loading patterns.
PMID- 29945842
TI - Utility of Prolotherapy for Upper Extremity Pathology.
AB - Prolotherapy is a method of treatment of painful musculoskeletal conditions
whereby a sclerosing agent is injected into an area of tendinosis or
osteoarthritis to strengthen and repair painful connective tissue. It is a safe,
effective, and relatively inexpensive nonsurgical treatment modality. This
article provides a history of prolotherapy, discusses its proposed mechanisms of
action, and provides a review of the existing literature on prolotherapy as a
treatment for upper extremity pathologies, specifically, hand osteoarthritis,
lateral epicondylitis, and rotator cuff disease.
PMID- 29945843
TI - Mental and Physical Health Disparities in Patients With Carpal Tunnel Syndrome
Living With High Levels of Social Deprivation.
AB - PURPOSE: Social, mental, and physical health have a complex interrelationship
with each influencing individuals' overall health experience. Social
circumstances have been shown to influence symptom intensity and magnitude of
disability for a variety of medical conditions. We tested the null hypothesis
that social deprivation would not impact Patient-Reported Outcomes Measurement
Information System (PROMIS) scores or objective health factors in patients
presenting for treatment of carpal tunnel syndrome (CTS). METHODS: This cross
sectional study analyzed data from 367 patients who presented for evaluation of
CTS to 1 of 6 hand surgeons at a tertiary academic center between August 1, 2016,
and June 30, 2017. Patients completed PROMIS Physical Function-v1.2, Pain
Interference-v1.1, Depression-v1.0, and Anxiety-v1.0 Computer Adaptive Tests. The
Area Deprivation Index was used to quantify social deprivation. Medical record
review determined duration of symptoms, tobacco and opioid use, and the Charlson
Comorbidity Index (CCI) for each patient. Sample demographics, PROMIS scores, and
objective health measures were compared in groups defined by national quartiles
of social deprivation. RESULTS: Patients with CTS living in the most deprived
quartile had worse mean scores across all 4 PROMIS domains compared with those
living in the least deprived quartile. A higher proportion of individuals from
the most deprived quartile had a heightened level of anxiety than those in the
least deprived quartile (37.3% vs 12.6%). The mean CCI was higher in the most
deprived quartile, as was the proportion of individuals using tobacco. There were
no differences in opioid use or symptom duration between patients from each
deprivation quartile. CONCLUSIONS: Social deprivation is associated with worse
patient-reported health measures in patients with CTS. Compared with those from
the least deprived areas, patients from the most deprived areas also have a
greater comorbidity burden and higher rates of tobacco use at presentation to a
hand surgeon. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.
PMID- 29945844
TI - Illuminating GPCR Signaling by Cryo-EM.
AB - The wave of resolution revolution in cryo-EM has touched, and made a significant
impact on, the structural biology of GPCRs. High-resolution structures of several
GPCR-G-protein complexes are now determined by cryo-EM and they illuminate fine
structural details of this central macromolecular complex involved in cellular
signaling.
PMID- 29945845
TI - Clinical impact of the updated international postoperative pancreatic fistula
definition in distal pancreatectomy.
AB - BACKGROUND: Postoperative pancreatic fistula (POPF) remains the most common
complication after distal pancreatectomy. The International Study Group on
Pancreatic Surgery definition of POPF is used worldwide. Recently, an update of
the definition was published. The aim of this study was to determine the clinical
impact of the update. METHODS: An international retrospective validation study,
including patients who underwent DP (2005 -2016) in 5 centers was performed.
Distribution of complications amongst POPF grades were compared for the old and
updated definition. RESULTS: In total, 1089 patients were included. The incidence
of POPF decreased with the updated definition from 47% to 24% (P < 0.01), largely
because a downgrade of grade A and grade B into biochemical leak. Comparable
morbidity was seen in the old and updated 'no POPF group' (Clavien -Dindo 3 5%
vs. 6% P = 0.320 and hospital stay (7 vs. 7 days P = 0.301). The change in
definition of POPF grade B resulted in more Clavien -Dindo 3 (38% vs. 51%) P <
0.01) and longer hospital stay (9 [9 -13] vs. 9 days [7 -15] P < 0.01) in the
updated 'grade B group'. CONCLUSION: Applying the updated POPF definition showed
improved discrimination between grades and should therefore be used to report
POPF after DP.
PMID- 29945846
TI - Preoperative Risk Assessment to Guide Prophylaxis and Reduce the Incidence of
Postoperative Nausea and Vomiting.
AB - PURPOSE: This article describes the implementation of a postoperative nausea and
vomiting (PONV) risk prediction and prophylaxis protocol. DESIGN: This is a
retrospective pre/post implementation quality improvement project. METHODS: This
project used chart reviews to assess the impact of the implemented PONV
assessment and prophylaxis in a sample population of adult females undergoing
gynecologic surgical procedures. FINDINGS: The mean number of prophylactic
antiemetics administered significantly increased during the postimplementation
period from 3.64 (SD, 0.878) in the preimplementation period to 4.07 (SD, 1.021)
in the postimplementation period (P < .001). The greatest increase in antiemetic
administration occurred in the moderate-risk (risk score, 4) and the high-risk
(risk score, 5 to 6) groups. The incidence of PONV decreased from 32.3% in the
preimplementation period to 28.9% in the postimplementation period; however, this
reduction did not meet statistical significance. Antiemetic administration
compliance increased from 37% in the preimplementation group to 61% in the
postimplementation group (P < .001). CONCLUSIONS: The results of this project
suggest that a risk-tailored approach to PONV prophylaxis using a risk assessment
tool along with treatment recommendations is effective at reducing the incidence
of PONV. The effectiveness of this approach is limited by the involvement of the
anesthesia providers responsible for completing the assessments and administering
PONV prophylaxis.
PMID- 29945847
TI - Difficult Airways: Key Factors for Successful Management.
AB - PURPOSE: To describe anesthetic nurses' experiences of key factors for the
successful management of difficult airways in adult patients. DESIGN: This study
had a qualitative observational and descriptive design following the critical
incident technique. METHODS: Twelve experienced anesthetic nurses were
interviewed. FINDINGS: We identified five key factors for the successful
management of difficult airways: identification of the difficult airway, creating
a plan of action, remaining calm and focusing on the task, technical skills, and
using the equipment. Identification of the difficult airway implies preassessment
with standardized methods and actively observing for signs indicative of a
difficult airway. Having all equipment available at bedside during induction and
creating a backup plan increases the action force in unexpected situations. A
calm and methodical work procedure facilitates the management of the difficult
airway as well as selecting techniques and equipment according to the patient and
situation. CONCLUSIONS: Reflective practice can aid the anesthetic nurse in
drawing on experience and remaining calm in acute situations.
PMID- 29945848
TI - Exploring an optimal risk adjustment model for public reporting of cesarean
section surgical site infections.
AB - BACKGROUND: Public report of surgical site infections (SSI) rates has been an
important component of SSI reduction strategies, and risk adjustment is needed
before SSI rates are publicly reported. Improving the risk adjustment model
facilitates meaningful comparison in the public reporting of SSIs. This research
aimed to explore an optimal risk adjustment model for the public reporting of
cesarean section (CS) SSI. METHODS: Information on 2506 cases of CS performed at
T hospital, a tertiary general hospital located in the W City of H Province in
China, from 01 January 2013 to 31 December 2014 was collected. The data were used
to construct the multivariate risk adjustment models of CS SSI through logistic
and Poisson stepwise regression. The c-index was used to compare the predictive
power between the new logistic regression and the National Nosocomial Infections
Surveillance (NNIS) risk index model. Pearson goodness-of-fit was determined to
compare the goodness-of-fit between the new Poisson regression and the NNIS risk
index model. The two new regression models were also compared. RESULTS: The
logistic and Poisson regression models included two patient-related risk factors,
namely, BMI (OR=1.085, P=0.006; RR=1.081, P=0.006) and ASA score (OR=1.522,
P=0.044; RR=1.501, P=0.047). The c-index of the logistic regression model (0.628)
was higher than that of the NNIS risk index model (0.600). The goodness-of-fit of
the Poisson regression model (0.946) was better than that of the NNIS risk index
model (0.851). CONCLUSIONS: The logistic and Poisson regression risk models are
better than the NNIS risk index model, implying that a multifactorial risk
adjustment model is needed for the public reporting of CS SSI. The advantage of
logistic regression model is that the predictive power of model can be evaluated
by c-index, however, Poisson regression may offer more advantages on model
accuracy than logistic regression does when the infection rate decreases.
PMID- 29945850
TI - The predictive value of cardiac morphology for long-term outcome of patients
undergoing catheter ablation for atrial fibrillation.
AB - OBJECTIVE: Catheter ablation (CA) is an established therapy for selected patients
with atrial fibrillation (AF), but predictors of CA ablation outcome are still
not fully elucidated. The aim of the study was to identify structural and
morphological parameters from computed tomography (CT) as predictors of
successful CA of AF in a single center prospective cohort. METHODS: An analysis
of CT scans dedicated to LA evaluation was performed in 99 patients (63 +/- 8
years old, 70% males, 59% paroxysmal AF) scheduled for CA of AF. Survival free of
atrial fibrillation/flutter/tachycardia at 1- and 3-years was assessed. RESULTS:
In overall study population, both 1- and 3-year responders had smaller distance
to the first division in left superior pulmonary vein (16.3 +/- 5.42 mm vs. 19.1
+/- 7.0 mm and 14.9 +/- 3.6 mm vs. 18.7 +/- 7.0 mm; p < 0.05). One-year
responders had larger ostium area of left inferior pulmonary vein (median 236 mm2
[IQR = 97] vs. 222 mm2 [IQR = 71]; p = 0.03) and less acute angle between the
interatrial septum and the right superior pulmonary vein (102 +/- 20 degrees vs.
95 +/- 10 degrees ; p = 0.03). Three-years' responders had smaller ostium area of
the right superior pulmonary vein (248 +/- 94 mm2 vs. 364 +/- 282 mm2; p = 0.02).
Multivariate Cox regression analysis identified different predictors in
paroxysmal and non-paroxysmal AF. For patients with paroxysmal AF, the predictors
were angle to right superior pulmonary vein and left superior/inferior pulmonary
veins carina thickness with hazard ratios of 0.965 (95%CI 0.939 to 0.992, p =
0.010) and 0.747 (95%CI 0.591 to 0.944, p = 0.015). In patients with persistent
AF, the predictors were gender and NYHA stage with hazard ratios of 4.9 (95%CI
1.758 to 13.579, p = 0.002) and 0.365 (95%CI 0.148 to 0.899, p = 0.028)
respectively. CONCLUSIONS: The anatomy of LA, especially morphology of pulmonary
veins, seems to be one of the predictors of clinical outcome after CA for
paroxysmal AF. In non-paroxysmal AF LA anatomy is less relevant in prediction of
clinical outcome.
PMID- 29945851
TI - A Cluster-Randomized Trial of a Mobile Produce Market Program in 12 Communities
in North Carolina: Program Development, Methods, and Baseline Characteristics.
AB - BACKGROUND: Mobile markets are an increasingly popular method for providing
access to fresh fruits and vegetables (F/V) in underserved communities; however,
evaluation of these programs is limited, as are descriptions of their
development, study designs, and needs of the populations they serve. OBJECTIVE:
Our aim was to describe the development and theoretical basis for Veggie Van
(VV), a mobile produce market intervention, the study design for the VV
evaluation, and baseline characteristics of the study population. DESIGN: The
protocol and sample for a cluster-randomized controlled trial with 12 sites are
described. PARTICIPANTS/SETTING: Community partner organizations in the Triangle
region of North Carolina that primarily served lower-income families or were
located in areas that had limited access to fresh produce were recruited.
Eligible individuals at each site (older than 18 years of age, self-identified as
the main shoppers for their household, and expressed interest in using a mobile
market) were targeted for enrollment. A total of 201 participants at 12 sites
participated in the VV program and evaluation, which was implemented from
November 2013 to March 2016. MAIN OUTCOME MEASURES: Change in F/V intake
(cups/day), derived from self-reported responses to the National Cancer Institute
F/V screener, was the main outcome measure. STATISTICAL ANALYSES PERFORMED: We
performed a descriptive analysis of baseline sample characteristics. RESULTS:
Mean reported F/V intake was 3.4 cups/day. Participants reported generally having
some access to fresh F/V, and 57.7% agreed they could afford enough F/V to feed
their family. The most frequently cited barriers were cost (55.7%) and time to
prepare F/V (20.4%). Self-efficacy was lowest for buying more F/V than usual and
trying new vegetables. CONCLUSIONS: By addressing cost and convenience and
building skills for purchasing and preparing F/V, the VV has the potential to
improve F/V consumption in underserved communities.
PMID- 29945852
TI - Assessing Clinical Judgment and Critical Thinking Skills in a Group of
Experienced Integrative and Functional Nutrition Registered Dietitian
Nutritionists.
PMID- 29945853
TI - Latino Fathers' Perspectives and Parenting Practices Regarding Eating, Physical
Activity, and Screen Time Behaviors of Early Adolescent Children: Focus Group
Findings.
AB - BACKGROUND: Involvement of Latino fathers in food and activity parenting
practices has implications for child obesity prevention yet remains largely
unknown. OBJECTIVE: To explore Latino fathers' perspectives and parenting
experiences regarding early adolescents' eating, physical activity, and screen
time behaviors using the focus group method. DESIGN: Twenty-six fathers
(primarily Mexican-American men) of 10- to 14-year-old children participated in
one of four focus groups between March and October 2016. Focus groups were
conducted in Spanish by male moderators. PARTICIPANTS/SETTINGS: A convenience
sample was recruited from three community centers and one charter school in
Minneapolis/St Paul, MN. ANALYSIS: Audiotaped focus groups were transcribed
verbatim in Spanish and translated to English; transcripts were coded and
analyzed for themes based on the grounded theory approach. RESULTS: Three themes
emerged including 1) paternal beliefs and concerns about early adolescents' diet,
physical activity, and screen time; 2) paternal food and activity parenting
practices; and 3) factors that may influence paternal involvement in promoting
healthy lifestyle behaviors. Father-reported food and activity parenting
practices included setting expectations and limits, role modeling, managing
availability and accessibility, teaching and reasoning, monitoring, motivating,
and doing things together. Factors influencing paternal involvement were
identified at intrapersonal, interpersonal, and social-environmental levels,
which included paternal dietary and activity behaviors, self-efficacy, time and
financial constraints, parental congruency, child resistance, perceived gender
role, and environmental challenges. CONCLUSIONS: Fathers identified eight major
food and activity parenting practices they use to promote a healthy lifestyle for
their adolescent children and factors that influence their involvement. Health
care professionals can use this information to provide culturally appropriate and
specific interventions for Latino American fathers of young adolescents.
PMID- 29945854
TI - Practice Roles and Characteristics of Integrative and Functional Nutrition
Registered Dietitian Nutritionists.
PMID- 29945849
TI - Impact of the International Nosocomial Infection Control Consortium (INICC)'s
multidimensional approach on rates of ventilator-associated pneumonia in
intensive care units in 22 hospitals of 14 cities of the Kingdom of Saudi Arabia.
AB - BACKGROUND: To analyze the impact of the International Nosocomial Infection
Control Consortium (INICC) Multidimensional Approach (IMA) and use of INICC
Surveillance Online System (ISOS) on ventilator-associated pneumonia (VAP) rates
in Saudi Arabia from September 2013 to February 2017. METHODS: A multicenter,
prospective, before-after surveillance study on 14,961 patients in 37 intensive
care units (ICUs) of 22 hospitals. During baseline, we performed outcome
surveillance of VAP applying the definitions of the CDC/NHSN. During
intervention, we implemented the IMA and the ISOS, which included: (1) a bundle
of infection prevention practice interventions, (2) education, (3) outcome
surveillance, (4) process surveillance, (5) feedback on VAP rates and
consequences and (6) performance feedback of process surveillance. Bivariate and
multivariate regression analyses were performed using generalized linear mixed
models to estimate the effect of intervention. RESULTS: The baseline rate of 7.84
VAPs per 1000 mechanical-ventilator (MV)-days-with 20,927 MV-days and 164 VAPs-,
was reduced to 4.74 VAPs per 1000 MV-days-with 118,929 MV-days and 771 VAPs-,
accounting for a 39% rate reduction (IDR 0.61; 95% CI 0.5-0.7; P 0.001).
CONCLUSIONS: Implementing the IMA was associated with significant reductions in
VAP rates in ICUs of Saudi Arabia.
PMID- 29945856
TI - Towards an Artificially Empathic Conversational Agent for Mental Health
Applications: System Design and User Perceptions.
AB - BACKGROUND: Conversational agents cannot yet express empathy in nuanced ways that
account for the unique circumstances of the user. Agents that possess this
faculty could be used to enhance digital mental health interventions. OBJECTIVE:
We sought to design a conversational agent that could express empathic support in
ways that might approach, or even match, human capabilities. Another aim was to
assess how users might appraise such a system. METHODS: Our system used a corpus
based approach to simulate expressed empathy. Responses from an existing pool of
online peer support data were repurposed by the agent and presented to the user.
Information retrieval techniques and word embeddings were used to select
historical responses that best matched a user's concerns. We collected ratings
from 37,169 users to evaluate the system. Additionally, we conducted a controlled
experiment (N=1284) to test whether the alleged source of a response (human or
machine) might change user perceptions. RESULTS: The majority of responses
created by the agent (2986/3770, 79.20%) were deemed acceptable by users.
However, users significantly preferred the efforts of their peers (P<.001). This
effect was maintained in a controlled study (P=.02), even when the only
difference in responses was whether they were framed as coming from a human or a
machine. CONCLUSIONS: Our system illustrates a novel way for machines to
construct nuanced and personalized empathic utterances. However, the design had
significant limitations and further research is needed to make this approach
viable. Our controlled study suggests that even in ideal conditions, nonhuman
agents may struggle to express empathy as well as humans. The ethical
implications of empathic agents, as well as their potential iatrogenic effects,
are also discussed.
PMID- 29945855
TI - YouTube Videos as a Source of Information About Clinical Trials: Observational
Study.
AB - BACKGROUND: Clinical trials are essential to the advancement of cancer treatment
but fewer than 5% of adult cancer patients enroll in a trial. A commonly cited
barrier to participation is the lack of understanding about clinical trials.
OBJECTIVE: Since the internet is a popular source of health-related information
and YouTube is the second most visited website in the world, we examined the
content of the top 115 YouTube videos about clinical trials to evaluate clinical
trial information available through this medium. METHODS: YouTube videos posted
prior to March 2017 were searched using selected keywords. A snowballing
technique was used to identify videos wherein sequential screening of the
autofill search results for each set of keywords was conducted. Video
characteristics (eg, number of views and video length) were recorded. The content
was broadly grouped as related to purpose, phases, design, safety and ethics, and
participant considerations. Stepwise multivariable logistic regression analysis
was conducted to assess associations between video type (cancer vs noncancer) and
video characteristics and content. RESULTS: In total, 115 videos were reviewed.
Of these, 46/115 (40.0%) were cancer clinical trials videos and 69/115 (60.0%)
were noncancer/general clinical trial videos. Most videos were created by health
care organizations/cancer centers (34/115, 29.6%), were oriented toward patients
(67/115, 58.3%) and the general public (68/115, 59.1%), and were informational
(79/115, 68.7%); altruism was a common theme (31/115, 27.0%). Compared with
noncancer videos, cancer clinical trials videos more frequently used an affective
communication style and mentioned the benefits of participation. Cancer clinical
trial videos were also much more likely to raise the issue of costs associated
with participation (odds ratio [OR] 5.93, 95% CI 1.15-29.46) and advise patients
to communicate with their physician about cancer clinical trials (OR 4.94, 95% CI
1.39-17.56). CONCLUSIONS: Collectively, YouTube clinical trial videos provided
information on many aspects of trials; however, individual videos tended to focus
on selected topics with varying levels of detail. Cancer clinical trial videos
were more emotional in style and positive in tone and provided information on the
important topics of cost and communication. Patients are encouraged to verify and
supplement YouTube video information in consultations with their health care
professionals to obtain a full and accurate picture of cancer clinical trials to
make an adequately informed decision about participation.
PMID- 29945857
TI - Web-Based Versus Usual Care and Other Formats of Decision Aids to Support
Prostate Cancer Screening Decisions: Systematic Review and Meta-Analysis.
AB - BACKGROUND: Prostate cancer is a leading cause of cancer among men. Because
screening for prostate cancer is a controversial issue, many experts in the field
have defended the use of shared decision making using validated decision aids,
which can be presented in different formats (eg, written, multimedia, Web).
Recent studies have concluded that decision aids improve knowledge and reduce
decisional conflict. OBJECTIVE: This meta-analysis aimed to investigate the
impact of using Web-based decision aids to support men's prostate cancer
screening decisions in comparison with usual care and other formats of decision
aids. METHODS: We searched PubMed, CINAHL, PsycINFO, and Cochrane CENTRAL
databases up to November 2016. This search identified randomized controlled
trials, which assessed Web-based decision aids for men making a prostate cancer
screening decision and reported quality of decision-making outcomes. Two
reviewers independently screened citations for inclusion criteria, extracted
data, and assessed risk of bias. Using a random-effects model, meta-analyses were
conducted pooling results using mean differences (MD), standardized mean
differences (SMD), and relative risks (RR). RESULTS: Of 2406 unique citations, 7
randomized controlled trials met the inclusion criteria. For risk of bias,
selective outcome reporting and participant/personnel blinding were mostly rated
as unclear due to inadequate reporting. Based on seven items, two studies had
high risk of bias for one item. Compared to usual care, Web-based decision aids
increased knowledge (SMD 0.46; 95% CI 0.18-0.75), reduced decisional conflict (MD
-7.07%; 95% CI -9.44 to -4.71), and reduced the practitioner control role in the
decision-making process (RR 0.50; 95% CI 0.31-0.81). Web-based decision aids
compared to printed decision aids yielded no differences in knowledge, decisional
conflict, and participation in decision or screening behaviors. Compared to video
decision aids, Web-based decision aids showed lower average knowledge scores (SMD
-0.50; 95% CI -0.88 to -0.12) and a slight decrease in prostate-specific antigen
screening (RR 1.12; 95% CI 1.01-1.25). CONCLUSIONS: According to this analysis,
Web-based decision aids performed similarly to alternative formats (ie, printed,
video) for the assessed decision-quality outcomes. The low cost, readiness,
availability, and anonymity of the Web can be an advantage for increasing access
to decision aids that support prostate cancer screening decisions among men.
PMID- 29945859
TI - Using a Virtual Reality Social Network During Awake Craniotomy to Map Social
Cognition: Prospective Trial.
AB - BACKGROUND: In awake craniotomy, it is possible to temporarily inactivate regions
of the brain using direct electrical stimulation, while the patient performs
neuropsychological tasks. If the patient shows decreased performance in a given
task, the neurosurgeon will not remove these regions, so as to maintain all brain
functions. OBJECTIVE: The objective of our study was to describe our experience
of using a virtual reality (VR) social network during awake craniotomy and
discuss its future applications for perioperative mapping of nonverbal language,
empathy, and theory of mind. METHODS: This was a single-center, prospective,
unblinded trial. During wound closure, different VR experiences with a VR headset
were proposed to the patient. This project sought to explore interactions with
the neuropsychologist's avatar in virtual locations using a VR social network as
an available experience. RESULTS: Three patients experienced VR. Despite some
limitations due to patient positioning during the operation and the limitation of
nonverbal cues inherent to the app, the neuropsychologist, as an avatar, could
communicate with the patient and explore gesture communication while wearing a VR
headset. CONCLUSIONS: With some improvements, VR social networks can be used in
the near future to map social cognition during awake craniotomy. TRIAL
REGISTRATION: ClinicalTrials.gov NCT03010943;
https://clinicaltrials.gov/ct2/show/NCT03010943 (Archived at WebCite at
http://www.webcitation.org/70CYDil0P).
PMID- 29945858
TI - eMental Healthcare Technologies for Anxiety and Depression in Childhood and
Adolescence: Systematic Review of Studies Reporting Implementation Outcomes.
AB - BACKGROUND: Anxiety disorders and depression are frequent conditions in childhood
and adolescence. eMental healthcare technologies may improve access to services,
but their uptake within health systems is limited. OBJECTIVE: The objective of
this review was to examine and describe how the implementation of eMental
healthcare technologies for anxiety disorders and depression in children and
adolescents has been studied. METHODS: We conducted a search of 5 electronic
databases and gray literature. Eligible studies were those that assessed an
eMental healthcare technology for treating or preventing anxiety or depression,
included children or adolescents (<18 years), or their parents or healthcare
providers and reported findings on technology implementation. The methodological
quality of studies was evaluated using the Mixed Methods Appraisal Tool. Outcomes
of interest were based on 8 implementation outcomes: acceptability (satisfaction
with a technology), adoption (technology uptake and utilization), appropriateness
("fitness for purpose"), cost (financial impact of technology implementation),
feasibility (extent to which a technology was successfully used), fidelity
(implementation as intended), penetration ("spread" or "reach" of the
technology), and sustainability (maintenance or integration of a technology
within a healthcare service). For extracted implementation outcome data, we coded
favorable ratings on measurement scales as "positive results" and unfavorable
ratings on measurement scales as "negative results." Those studies that reported
both positive and negative findings were coded as having "mixed results."
RESULTS: A total of 46 studies met the inclusion criteria, the majority of which
were rated as very good to excellent in methodological quality. These studies
investigated eMental healthcare technologies for anxiety (n=23), depression
(n=18), or both anxiety and depression (n=5). Studies of technologies for anxiety
evaluated the following: (1) acceptability (78%) reported high levels of
satisfaction, (2) adoption (43%) commonly reported positive results, and (3)
feasibility (43%) reported mixed results. Studies of technologies for depression
evaluated the following: (1) appropriateness (56%) reported moderate helpfulness
and (2) acceptability (50%) described a mix of both positive and negative
findings. Studies of technologies designed to aid anxiety and depression commonly
reported mixed experiences with acceptability and adoption and positive findings
for appropriateness of the technologies for treatment. Across all studies, cost,
fidelity, and penetration and sustainability were the least measured
implementation outcomes. CONCLUSIONS: Acceptability of eMental healthcare
technology is high among users and is the most commonly investigated
implementation outcome. Perceptions of the appropriateness and adoption of
eMental healthcare technology were varied. Implementation research that
identifies, evaluates, and reports on costs, sustainability, and fidelity to
clinical guidelines is crucial for making high-quality eMental healthcare
available to children and adolescents.
PMID- 29945860
TI - Validation of a Novel Electronic Health Record Patient Portal Advance Care
Planning Delivery System.
AB - BACKGROUND: Advance care planning allows patients to articulate their future care
preferences should they no longer be able to make decisions on their own. Early
advance care planning in outpatient settings provides benefits such as less
aggressive care and fewer hospitalizations, yet it is underutilized due to
barriers such as provider time constraints and communication complexity. Novel
methods, such as patient portals, provide a unique opportunity to conduct advance
care planning previsit planning for outpatient care. This follow-up to our pilot
study aimed to conduct pragmatic testing of a novel electronic health record
tethered framework and its effects on advance care planning delivery in a real
world primary care setting. OBJECTIVE: Our intervention tested a previsit advance
care planning workflow centered around a framework sent via secure electronic
health record-linked patient portal in a real-world clinical setting. The primary
objective of this study was to determine its impact on frequency and quality of
advance care planning documentation. METHODS: We conducted a pragmatic trial
including 2 sister clinical sites, one site implementing the intervention and the
other continuing standard care. A total of 419 patients aged between 50 and 93
years with active portal accounts received intervention (n=200) or standard care
(n=219). Chart review analyzed the presence of advance care planning and its
quality and was graded with previously established scoring criteria based on
advance care planning best practice guidelines from multiple nations. RESULTS: A
total of 19.5% (39/200) of patients who received previsit planning responded to
the framework. We found that the intervention site had statistically significant
improvement in new advance care planning documentation rates (P<.01) and quality
(P<.01) among all eligible patients. Advance care planning documentation rates
increased by 105% (19/39 to 39/39) and quality improved among all patients who
engaged in the previsit planning framework (n=39). Among eligible patients aged
between 50 and 60 years at the intervention site, advance care planning
documentation rates increased by 37% (27/96 to 37/96). Advance care planning
documentation rates increased 34% among high users (27/67 to 36/67). CONCLUSIONS:
Advance care planning previsit planning using a secure electronic health record
supported patient portal framework yielded improvement in the presence of advance
care planning documentation, with highest improvement in active patient portal
users and patients aged between 50 and 60 years. Targeted previsit patient portal
advance care planning delivery in these populations can potentially improve the
quality of care in these populations.
PMID- 29945862
TI - Nurses' Experience With Health Information Technology: Longitudinal Qualitative
Study.
AB - BACKGROUND: Nurses are the largest group of health information technology (HIT)
users. As such, nurses' adaptations are critical for HIT implementation success.
However, longitudinal approaches to understanding nurses' perceptions of HIT
remain underexplored. Previous studies of nurses' perceptions demonstrate that
the progress and timing for acceptance of and adaptation to HIT varies.
OBJECTIVE: This study aimed to explore nurses' experience regarding
implementation of HIT over time. METHODS: A phenomenological approach was used
for this longitudinal qualitative study to explore nurses' perceptions of HIT
implementation over time, focusing on three time points (rounds) at 3, 9, and 18
months after implementation of electronic health records and bar code medication
administration. The purposive sample was comprised of clinical nurses who worked
on a medical-surgical unit in an academic center. RESULTS: Major findings were
categorized into 7 main themes with 54 subthemes. Nurses reported personal-level
and organizational-level factors that facilitated HIT adaptation. We also
generated network graphs to illustrate the occurrence of themes. Thematic
interconnectivity differed due to nurses' concerns and satisfaction at different
time points. Equipment and workflow were the most frequent themes across all
three rounds. Nurses were the most dissatisfied approximately 9 months after HIT
implementation. Eighteen months after HIT implementation, nurses' perceptions
appeared more balanced. CONCLUSIONS: It is recommended that organizations invest
in equipment (ie, wireless barcode scanners), refine policies to reflect nursing
practice, and improve systems to focus on patient safety. Future research is
necessary to confirm patterns of nurses' adaptation to HIT in other samples.
PMID- 29945861
TI - Testing a Smartphone App (Young with Diabetes) to Improve Self-Management of
Diabetes Over 12 Months: Randomized Controlled Trial.
AB - BACKGROUND: Young people often struggle to self-manage type 1 diabetes during the
transition from childhood to adulthood. Mobile health (mHealth) apps may have the
potential to support self-management, but evidence is limited and randomized
controlled trials are needed. OBJECTIVE: We assessed whether the mHealth app
"Young with Diabetes" improved young people's self-management measured by
glycated hemoglobin (HbA1c) and three self-reported psychometric scales. METHODS:
Young people (14-22 years) with inadequate glycemic control and their parents
were enrolled in a randomized controlled trial and assigned either to Young with
Diabetes and usual care (Young with Diabetes group) or to usual care alone
(control). Young with Diabetes use was monitored; functions included a chat room,
contact the health care provider, reminders, tips, information about the diabetes
department and type 1 diabetes topics, carbohydrate counting, and a parents'
section. Outcomes included HbA1c and three self-reported psychometric scales:
Perceived Competence in Diabetes Scale; Health Care Climate Questionnaire; and
Problem Areas In Diabetes care survey. Data were collected at baseline and at 2,
7, and 12 months. RESULTS: A total of 151 young people were randomized (Young
with Diabetes group=76, control=75) and 49 parents agreed to participate. At 12
months, HbA1c was significantly higher (4.1 mmol/mol; 0.4 %) in the Young with
Diabetes group, compared to the control group (P=.04); this finding did not occur
when comparing app users (Young with Diabetes use >=5 days) with nonusers. Young
people used Young with Diabetes on a mean of 10.5 days. They spent the most time
chatting about alcohol and searching for information about sex. Most young people
and half of the parents reported that Young with Diabetes helped them. More than
80% would recommend Young with Diabetes to peers. CONCLUSIONS: Young with
Diabetes did not improve HbA1c, but it may be a useful complement to self
management. Qualitative evaluation is needed to explore benefits and shortcomings
of Young with Diabetes. Health care providers should address young peoples'
knowledge about sensitive topics, provide them with peer support, and be aware of
parents' need for information about how to support. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02632383; https://clinicaltrials.gov/ct2/show/NCT02632383
(Archived by WebCite at http://www.webcitation.org/6zCK2u7xM).
PMID- 29945863
TI - SOX2 regulation by hedgehog signaling controls adult lingual epithelium
homeostasis.
AB - Adult tongue epithelium is continuously renewed from epithelial progenitor cells,
a process that requires hedgehog (HH) signaling. In mice, pharmacological
inhibition of the HH pathway causes taste bud loss within a few weeks.
Previously, we demonstrated that sonic hedgehog (SHH) overexpression in lingual
progenitors induces ectopic taste buds with locally increased SOX2 expression,
suggesting that taste bud differentiation depends on SOX2 downstream of HH. To
test this, we inhibited HH signaling in mice and observed a rapid decline in Sox2
and SOX2-GFP expression in taste epithelium. Upon conditional deletion of Sox2,
differentiation of both taste and non-taste epithelial cells was blocked, and
progenitor cell number increased. In contrast to basally restricted proliferation
in controls, dividing cells were overabundant and spread to suprabasal epithelial
layers in mutants. SOX2 loss in progenitors also led non-cell-autonomously to
taste cell apoptosis, dramatically shortening taste cell lifespans. Finally, in
tongues with conditional Sox2 deletion and SHH overexpression, ectopic and
endogenous taste buds were not detectable; instead, progenitor hyperproliferation
expanded throughout the lingual epithelium. In summary, we show that SOX2
functions downstream of HH signaling to regulate lingual epithelium homeostasis.
PMID- 29945864
TI - EED, a member of the polycomb group, is required for nephron differentiation and
the maintenance of nephron progenitor cells.
AB - Epigenetic regulation of gene expression has a crucial role allowing for the self
renewal and differentiation of stem and progenitor populations during
organogenesis. The mammalian kidney maintains a population of self-renewing stem
cells that differentiate to give rise to thousands of nephrons, which are the
functional units that carry out filtration to maintain physiological homeostasis.
The polycomb repressive complex 2 (PRC2) epigenetically represses gene expression
during development by placing the H3K27me3 mark on histone H3 at promoter and
enhancer sites, resulting in gene silencing. To understand the role of PRC2 in
nephron differentiation, we conditionally inactivated the Eed gene, which encodes
a nonredundant component of the PRC2 complex, in nephron progenitor cells.
Resultant kidneys were smaller and showed premature loss of progenitor cells. The
progenitors in Eed mutant mice that were induced to differentiate did not develop
into properly formed nephrons. Lhx1, normally expressed in the renal vesicle, was
overexpressed in kidneys of Eed mutant mice. Thus, PRC2 has a crucial role in
suppressing the expression of genes that maintain the progenitor state, allowing
nephron differentiation to proceed.
PMID- 29945866
TI - Differentiating cells mechanically limit the interkinetic nuclear migration of
progenitor cells to secure apical cytogenesis.
AB - Many proliferative epithelia are pseudostratified because of cell cycle-dependent
interkinetic nuclear migration (IKNM, basal during G1 and apical during G2).
Although most epithelia, including early embryonic neuroepithelia (<=100 um
thick), undergo IKNM over the entire apicobasal extent, more apicobasally
elongated (300 um) neural progenitor cells (radial glial cells) in the mid
embryonic mouse cerebral wall move their nuclei only within its apical (100 um)
compartment, leaving the remaining basal region nucleus-free (fiber-like). How
this IKNM range [i.e. the thickness of a pseudostratified ventricular zone (VZ)]
is determined remains unknown. Here, we report external fencing of IKNM and the
VZ by differentiating cells. When a tight stack of multipolar cells immediately
basal to the VZ was 'drilled' via acute neuron-directed expression of diphtheria
toxin, IKNM of apicobasally connected progenitor cells continued further towards
the basal region of the cell (200 um). The unfencing-induced basally overshot
nuclei stay in S phase for too long and do not move apically, suggesting that
external limitation of IKNM is necessary for progenitors to undergo normal
cytogenetic behaviors. Thus, physical collaboration between progenitors and
differentiating cells, including neurons, underlies brain development.
PMID- 29945865
TI - SLAM-ITseq: sequencing cell type-specific transcriptomes without cell sorting.
AB - Cell type-specific transcriptome analysis is an essential tool for understanding
biological processes in which diverse types of cells are involved. Although cell
isolation methods such as fluorescence-activated cell sorting (FACS) in
combination with transcriptome analysis have widely been used so far, their time
consuming and harsh procedures limit their applications. Here, we report a novel
in vivo metabolic RNA sequencing method, SLAM-ITseq, which metabolically labels
RNA with 4-thiouracil in a specific cell type in vivo followed by detection
through an RNA-seq-based method that specifically distinguishes the thiolated
uridine by base conversion. This method has successfully identified the cell type
specific transcriptome in three different tissues: endothelial cells in brain,
epithelial cells in intestine and adipocytes in white adipose tissue. As this
method does not require isolation of cells or RNA prior to the transcriptomic
analysis, SLAM-ITseq provides an easy yet accurate snapshot of the
transcriptional state in vivo.
PMID- 29945867
TI - Bsx controls pineal complex development.
AB - Neuroendocrine cells in the pineal gland release melatonin during the night and,
in teleosts, are directly photoreceptive. During development of the pineal
complex, a small number of cells migrate leftward away from the pineal anlage to
form the parapineal cell cluster, a process that is crucial for asymmetrical
development of the bilateral habenular nuclei. Here, we show that, throughout
zebrafish embryonic development, the brain-specific homeobox (bsx) gene is
expressed in all cell types of the pineal complex. We identified Bmp and Noto/Flh
as major regulators of bsx expression in the pineal complex. Upon loss of Bsx
through the generation of a targeted mutation, embryos fail to form a parapineal
organ and develop right-isomerized habenulae. Crucial enzymes in the melatonin
biosynthesis pathway are not expressed, suggesting the absence of melatonin from
the pineal gland in bsx mutants. Several genes involved in rod-like or cone-like
phototransduction are also abnormally expressed, indicating that Bsx has a
pivotal role in the differentiation of multiple cell types in the zebrafish
pineal complex.
PMID- 29945868
TI - Hedgehog-GLI signaling in Foxd1-positive stromal cells promotes murine
nephrogenesis via TGFbeta signaling.
AB - Normal kidney function depends on the proper development of the nephron: the
functional unit of the kidney. Reciprocal signaling interactions between the
stroma and nephron progenitor compartment have been proposed to control nephron
development. Here, we show that removal of hedgehog intracellular effector
smoothened (Smo-deficient mutants) in the cortical stroma results in an abnormal
renal capsule, and an expanded nephron progenitor domain with an accompanying
decrease in nephron number via a block in epithelialization. We show that stromal
hedgehog-Smo signaling acts through a GLI3 repressor. Whole-kidney RNA sequencing
and analysis of FACS-isolated stromal cells identified impaired TGFbeta2
signaling in Smo-deficient mutants. We show that neutralization and knockdown of
TGFbeta2 in explants inhibited nephrogenesis. In addition, we demonstrate that
concurrent deletion of Tgfbr2 in stromal and nephrogenic cells in vivo results in
decreased nephron formation and an expanded nephrogenic precursor domain similar
to that observed in Smo-deficient mutant mice. Together, our data suggest a
mechanism whereby a stromal hedgehog-TGFbeta2 signaling axis acts to control
nephrogenesis.
PMID- 29945869
TI - Oncogenic cooperation between Yorkie and the conserved microRNA miR-8 in the wing
disc of Drosophila.
AB - Tissue growth has to be carefully controlled to generate well-functioning organs.
MicroRNAs are small non-coding RNAs that modulate the activity of target genes
and play a pivotal role in animal development. Understanding the functions of
microRNAs in development requires the identification of their target genes. Here,
we find that miR-8, a conserved microRNA in the miR-200 family, controls tissue
growth and homeostasis in the Drosophila wing imaginal disc. Upregulation of miR
8 causes the repression of Yorkie, the effector of the Hippo pathway in
Drosophila, and reduces tissue size. Remarkably, co-expression of Yorkie and miR
8 causes the formation of neoplastic tumors. We show that upregulation of miR-8
represses the growth inhibitor brinker, and depletion of brinker cooperates with
Yorkie in the formation of neoplastic tumors. Hence, miR-8 modulates a positive
growth regulator, Yorkie, and a negative growth regulator, brinker Deregulation
of this network can result in the loss of tissue homeostasis and the formation of
tumors.
PMID- 29945870
TI - Cxcl12a induces snail1b expression to initiate collective migration and
sequential Fgf-dependent neuromast formation in the zebrafish posterior lateral
line primordium.
AB - The zebrafish posterior lateral line primordium migrates along a path defined by
the chemokine Cxcl12a, periodically depositing neuromasts, to pioneer formation
of the zebrafish posterior lateral line system. snail1b, known for its role in
promoting cell migration, is expressed in leading cells of the primordium in
response to Cxcl12a, whereas its expression in trailing cells is inhibited by Fgf
signaling. snail1b knockdown delays initiation of primordium migration. This
delay is associated with aberrant expansion of epithelial cell adhesion molecule
(epcam) and reduction of cadherin 2 expression in the leading part of the
primordium. Co-injection of snail1b morpholino with snail1b mRNA prevents the
initial delay in migration and restores normal expression of epcam and cadherin 2
The delay in initiating primordium migration in snail1b morphants is accompanied
by a delay in sequential formation of trailing Fgf signaling centers and
associated protoneuromasts. This delay is not specifically associated with
knockdown of snail1b but also with other manipulations that delay migration of
the primordium. These observations reveal an unexpected link between the
initiation of collective migration and sequential formation of protoneuromasts in
the primordium.
PMID- 29945871
TI - Conservation and divergence of YODA MAPKKK function in regulation of grass
epidermal patterning.
AB - All multicellular organisms must properly pattern cell types to generate
functional tissues and organs. The organized and predictable cell lineages of the
Brachypodium leaf enabled us to characterize the role of the MAPK kinase kinase
gene BdYODA1 in regulating asymmetric cell divisions. We find that YODA genes
promote normal stomatal spacing patterns in both Arabidopsis and Brachypodium,
despite species-specific differences in those patterns. Using lineage tracing and
cell fate markers, we show that, unexpectedly, patterning defects in bdyoda1
mutants do not arise from faulty physical asymmetry in cell divisions but rather
from improper enforcement of alternative cellular fates after division. These
cross-species comparisons allow us to refine our understanding of MAPK activities
during plant asymmetric cell divisions.
PMID- 29945872
TI - Leukocyte Differentiation by Histidine-Rich Glycoprotein/Stanniocalcin-2 Complex
Regulates Murine Glioma Growth through Modulation of Antitumor Immunity.
AB - The plasma-protein histidine-rich glycoprotein (HRG) is implicated in phenotypic
switching of tumor-associated macrophages, regulating cytokine production and
phagocytotic activity, thereby promoting vessel normalization and antitumor
immune responses. To assess the therapeutic effect of HRG gene delivery on CNS
tumors, we used adenovirus-encoded HRG to treat mouse intracranial GL261 glioma.
Delivery of Ad5-HRG to the tumor site resulted in a significant reduction in
glioma growth, associated with increased vessel perfusion and increased CD45+
leukocyte and CD8+ T-cell accumulation in the tumor. Antibody-mediated
neutralization of colony-stimulating factor-1 suppressed the effects of HRG on
CD45+ and CD8+ infiltration. Using a novel protein interaction-decoding
technology, TRICEPS-based ligand receptor capture (LRC), we identified
Stanniocalcin-2 (STC2) as an interacting partner of HRG on the surface of
inflammatory cells in vitro and colocalization of HRG and STC2 in gliomas. HRG
reduced the suppressive effects of STC2 on monocyte CD14+ differentiation and
STC2-regulated immune response pathways. In consequence, Ad5-HRG-treated gliomas
displayed decreased numbers of IL35+ Treg cells, providing a mechanistic
rationale for the reduction in GL261 growth in response to Ad5-HRG delivery. We
conclude that HRG suppresses glioma growth by modulating tumor inflammation
through monocyte infiltration and differentiation. Moreover, HRG acts to balance
the regulatory effects of its partner, STC2, on inflammation and innate and/or
acquired immunity. HRG gene delivery therefore offers a potential therapeutic
strategy to control antitumor immunity. Mol Cancer Ther; 17(9); 1961-72. (c)2018
AACR.
PMID- 29945875
TI - Effect of initial body orientation on escape probability of prey fish escaping
from predators.
AB - The kinematic and behavioral components of the escape response can affect the
outcomes of predator-prey interactions. For example, because sensory perception
range can have spatial bias, and because turn duration before the initiation of
escape locomotion can be smaller when prey is oriented away from predators, the
prey's body orientation relative to a predator at the onset of the escape
response (initial orientation) could affect whether prey successfully evade
predators. We tested this hypothesis by recording the escape responses of
juvenile red sea bream (Pagrus major) to the predatory scorpion fish (Sebastiscus
marmoratus). Flight initiation distance tended to be small when prey were
attacked from behind, suggesting that prey have spatial bias in detecting
attacking predators. An increase in flight initiation distance increased escape
probability. An increase in initial orientation decreased turn duration and
increased escape probability when the effect of flight initiation distance was
offset. These results suggest that initial orientation affects escape probability
through two different pathways: changes in flight initiation distance and turn
duration. These findings highlight the importance of incorporating initial
orientation into other studies of the kinematics of predator-prey interactions.
PMID- 29945874
TI - EB1 contributes to microtubule bundling and organization, along with root growth,
in Arabidopsis thaliana.
AB - Microtubules are involved in plant development and adaptation to their
environment, but the sustaining molecular mechanisms remain elusive. Microtubule
end-binding 1 (EB1) proteins participate in directional root growth in
Arabidopsis thaliana However, a connection to the underlying microtubule array
has not been established yet. We show here that EB1 proteins contribute to the
organization of cortical microtubules in growing epidermal plant cells, without
significant modulation of microtubule dynamics. Using super-resolution stimulated
emission depletion (STED) microscopy and an original quantification approach, we
also demonstrate a significant reduction of apparent microtubule bundling in
cytoplasmic-EB1-deficient plants, suggesting a function for EB1 in the
interaction between adjacent microtubules. Furthermore, we observed root growth
defects in EB1-deficient plants, which are not related to cell division
impairment. Altogether, our results support a role for EB1 proteins in root
development, in part by maintaining the organization of cortical
microtubules.This article has an associated First Person interview with the first
author of the paper.
PMID- 29945873
TI - Characterization of a cdc14 null allele in Drosophila melanogaster.
AB - Cdc14 is an evolutionarily conserved serine/threonine phosphatase. Originally
identified in Saccharomyces cerevisiae as a cell cycle regulator, its role in
other eukaryotic organisms remains unclear. In Drosophila melanogaster, Cdc14 is
encoded by a single gene, thus facilitating its study. We found that Cdc14
expression is highest in the testis of adult flies and that cdc14 null flies are
viable. cdc14 null female and male flies do not display altered fertility. cdc14
null males, however, exhibit decreased sperm competitiveness. Previous studies
have shown that Cdc14 plays a role in ciliogenesis during zebrafish development.
In Drosophila, sensory neurons are ciliated. We found that the Drosophila cdc14
null mutants have defects in chemosensation and mechanosensation as indicated by
decreased avoidance of repellant substances and decreased response to touch. In
addition, we show that cdc14 null mutants have defects in lipid metabolism and
resistance to starvation. These studies highlight the diversity of Cdc14 function
in eukaryotes despite its structural conservation.
PMID- 29945876
TI - Coagulation factor 9-deficient mice are protected against dextran sulfate sodium
induced colitis.
AB - Patients with inflammatory bowel disease (IBD) are susceptible to
thromboembolism. Interestingly, IBD occurs less frequently in patients with
inherited bleeding disorders. Therefore, we analyzed whether F9-deficiency is
protective against the onset of acute colitis in a genetic hemophilia B mouse
model. In the 3.5% dextran sulfate sodium (DSS)-induced colitis model, F9
deficient mice were protected from body-weight loss and had a reduced disease
activity score. We detected decreased colonic myeloperoxidase activity and
decreased CXCL1 levels in DSS-treated F9-deficient mice compared with wild-type
(WT) littermate controls, indicating decreased neutrophil infiltration.
Remarkably, we identified expression of coagulation factor IX (FIX) protein in
small intestinal epithelial cells (MODE-K). In epithelial cell cultures, cellular
FIX protein expression was increased following stimulation with the bacterial
Toll-like receptor agonists lipopolysaccharide, macrophage-activating lipopeptide
2 and Pam3CSK4. Thus, we revealed a protective role of F9-deficiency in DSS
induced colitis and identified the intestinal epithelium as a site of ectopic
FIX.This article has an associated First Person interview with the first author
of the paper.
PMID- 29945878
TI - Inflammatory neuropathies: all shapes and sizes.
PMID- 29945877
TI - Oxytocin receptor signaling contributes to olfactory avoidance behavior induced
by an unpleasant odorant.
AB - Oxytocin (OXT) and its receptor (OXTR) regulate reproductive physiology (i.e.
parturition and lactation), sociosexual behavior, learned patterns of behavior
and olfactory behavior in social contexts. To characterize the function of OXTR
in basic olfactory behavior, the present study compared the behavioral responses
of homozygous, heterozygous and wild-type mice when these mice were confronted
with an unpleasant odorant (butyric acid) in a custom-made Y-maze in the absence
of a social context. Wild-type mice avoided the first encounter with the butyric
acid odorant, whereas homozygous and heterozygous mice did not. However, both
heterozygous and wild-type mice habituated when confronted with the butyric
odorant again on the following 2 days. By contrast, homozygous mice failed to
habituate and instead avoided the location of the odorant for at least 3 days.
These data suggest that homozygous and heterozygous mice display abnormal
olfactory responses to the presentation of an unpleasant odorant. Our studies
demonstrate that OXTR plays a critical role in regulating olfactory behavior in
the absence of a social context.
PMID- 29945879
TI - Neurofascin-155 IgM autoantibodies in patients with inflammatory neuropathies.
AB - OBJECTIVES: Recently, IgG autoantibodies against different paranodal proteins
have been detected and this has led to important advances in the management of
inflammatory neuropathies. In contrast, not much is known on IgM autoantibodies
against paranodal proteins. METHODS: In the present study, we screened a large
cohort of patients (n=140) with inflammatory neuropathies for IgM autoantibodies
against neurofascin-155, neurofascin-186 or contactin-1. RESULTS: IgM
autoantibodies against neurofascin-155 were detected by ELISA in five patients,
four with inflammatory demyelinating polyradiculoneuropathy (CIDP) and one with
Guillain-Barre syndrome (GBS), and were confirmed by ELISA-based preabsorption
experiments and Western blot. Titres ranged from 1:100 to 1:400. We did not
detect IgM anti-neurofascin-186 or anti-contactin-1 antibodies in this cohort.
All patients presented with distally accentuated tetraparesis and hypesthesia.
Remarkably, tremor was present in three of the patients with CIDP and occurred in
the patients with GBS after the acute phase of disease. Nerve conduction studies
revealed prolonged distal motor latencies and F wave latencies. Nerve biopsies
showed signs of secondary axonal damage in three of the patients, demyelinating
features in one patient. Teased fibre preparations did not demonstrate paranodal
damage. CONCLUSION: In summary, IgM neurofascin-155 autoantibodies may be worth
testing in patients with inflammatory neuropathies. Their pathogenic role needs
to be determined in future experiments.
PMID- 29945880
TI - Clinical, electrophysiological and VEGF 2-year response after lenalidomide or
stem cell transplantation in patients with POEMS syndrome.
PMID- 29945881
TI - Structural characteristics of the central nervous system in Friedreich ataxia: an
in vivo spinal cord and brain MRI study.
PMID- 29945883
TI - MEG3-4 is a miRNA decoy that regulates IL-1beta abundance to initiate and then
limit inflammation to prevent sepsis during lung infection.
AB - Long noncoding RNAs (lncRNAs) regulate gene expression. We investigated the role
of lncRNAs in the inflammatory response to bacterial infection in the lungs. We
identified the lncRNA MEG3 as a tissue-specific modulator of inflammatory
responses during bacterial infection. Among the 10 transcript isoforms of MEG3,
transcript 4 (referred to as MEG3-4) encodes the isoform with the lowest
abundance in mouse lungs. Nonetheless, we found that MEG3-4 bound to the microRNA
miR-138 in a competitive manner with mRNA encoding the proinflammatory cytokine
interleukin-1beta (IL-1beta), thereby increasing IL-1beta abundance and
intensifying inflammatory responses to bacterial infection in alveolar
macrophages and lung epithelial cells in culture and in lung tissue in mice. MEG3
4-mediated sponging of miR-138 in the cytoplasm increased the autocrine activity
of IL-1beta that subsequently induced a negative feedback mechanism mediated by
nuclear factor kappaB that decreased MEG3-4 abundance and inflammatory cytokine
production. This timely reduction in MEG3-4 abundance tempered proinflammatory
responses in mice with pulmonary bacterial infection, preventing the progression
to sepsis. Together, these findings reveal that MEG3-4 dynamically modulates
pulmonary inflammatory responses through transcriptional regulation of immune
response genes, extending the decoy and sponge mechanism associated with lncRNAs
to antibacterial immunity, which affects both response and disease progression.
PMID- 29945884
TI - The plant cell wall integrity maintenance and immune signaling systems cooperate
to control stress responses in Arabidopsis thaliana.
AB - Cell walls surround all plant cells, and their composition and structure are
modified in a tightly controlled, adaptive manner to meet sometimes opposing
functional requirements during growth and development. The plant cell wall
integrity (CWI) maintenance mechanism controls these functional modifications, as
well as responses to cell wall damage (CWD). We investigated how the CWI system
mediates responses to CWD in Arabidopsis thaliana CWD induced by cell wall
degrading enzymes or an inhibitor of cellulose biosynthesis elicited similar,
turgor-sensitive stress responses. Phenotypic clustering with 27 genotypes
identified a core group of receptor-like kinases (RLKs) and ion channels required
for the activation of CWD responses. A genetic analysis showed that the RLK FEI2
and the plasma membrane-localized mechanosensitive Ca2+ channel MCA1 functioned
downstream of the RLK THE1 in CWD perception. In contrast, pattern-triggered
immunity (PTI) signaling components, including the receptors for plant elicitor
peptides (AtPeps) PEPR1 and PEPR2, repressed responses to CWD. CWD induced the
expression of PROPEP1 and PROPEP3, which encode the precursors of AtPep1 and
AtPep3, and the release of PROPEP3 into the growth medium. Application of AtPep1
and AtPep3 repressed CWD-induced phytohormone accumulation in a concentration
dependent manner. These results suggest that AtPep-mediated signaling suppresses
CWD-induced defense responses controlled by the CWI mechanism. This suppression
was alleviated when PTI signaling downstream of PEPR1 and PEPR2 was impaired.
Defense responses controlled by the CWI maintenance mechanism might thus
compensate to some extent for the loss of PTI signaling elements.
PMID- 29945882
TI - An atlas of chromatin accessibility in the adult human brain.
AB - Most common genetic risk variants associated with neuropsychiatric disease are
noncoding and are thought to exert their effects by disrupting the function of
cis regulatory elements (CREs), including promoters and enhancers. Within each
cell, chromatin is arranged in specific patterns to expose the repertoire of CREs
required for optimal spatiotemporal regulation of gene expression. To further
understand the complex mechanisms that modulate transcription in the brain, we
used frozen postmortem samples to generate the largest human brain and cell-type
specific open chromatin data set to date. Using the Assay for Transposase
Accessible Chromatin followed by sequencing (ATAC-seq), we created maps of
chromatin accessibility in two cell types (neurons and non-neurons) across 14
distinct brain regions of five individuals. Chromatin structure varies markedly
by cell type, with neuronal chromatin displaying higher regional variability than
that of non-neurons. Among our findings is an open chromatin region (OCR)
specific to neurons of the striatum. When placed in the mouse, a human sequence
derived from this OCR recapitulates the cell type and regional expression pattern
predicted by our ATAC-seq experiments. Furthermore, differentially accessible
chromatin overlaps with the genetic architecture of neuropsychiatric traits and
identifies differences in molecular pathways and biological functions. By
leveraging transcription factor binding analysis, we identify protein-coding and
long noncoding RNAs (lncRNAs) with cell-type and brain region specificity. Our
data provide a valuable resource to the research community and we provide this
human brain chromatin accessibility atlas as an online database "Brain Open
Chromatin Atlas (BOCA)" to facilitate interpretation.
PMID- 29945885
TI - Thyroid hormone receptor and ERRalpha coordinately regulate mitochondrial
fission, mitophagy, biogenesis, and function.
AB - Thyroid hormone receptor beta1 (THRB1) and estrogen-related receptor alpha
(ESRRA; also known as ERRalpha) both play important roles in mitochondrial
activity. To understand their potential interactions, we performed transcriptome
and ChIP-seq analyses and found that many genes that were co-regulated by both
THRB1 and ESRRA were involved in mitochondrial metabolic pathways. These included
oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and beta
oxidation of fatty acids. TH increased ESRRA expression and activity in a THRB1
dependent manner through the induction of the transcriptional coactivator
PPARGC1A (also known as PGC1alpha). Moreover, TH induced mitochondrial
biogenesis, fission, and mitophagy in an ESRRA-dependent manner. TH also induced
the expression of the autophagy-regulating kinase ULK1 through ESRRA, which then
promoted DRP1-mediated mitochondrial fission. In addition, ULK1 activated the
docking receptor protein FUNDC1 and its interaction with the autophagosomal
protein MAP1LC3B-II to induce mitophagy. siRNA knockdown of ESRRA, ULK1, DRP1, or
FUNDC1 inhibited TH-induced autophagic clearance of mitochondria through
mitophagy and decreased OXPHOS. These findings show that many of the
mitochondrial actions of TH are mediated through stimulation of ESRRA expression
and activity, and co-regulation of mitochondrial turnover through the PPARGC1A
ESRRA-ULK1 pathway is mediated by their regulation of mitochondrial fission and
mitophagy. Hormonal or pharmacologic induction of ESRRA expression or activity
could improve mitochondrial quality in metabolic disorders.
PMID- 29945887
TI - DPM-1001 decreased copper levels and ameliorated deficits in a mouse model of
Wilson's disease.
AB - The levels of copper, which is an essential element in living organisms, are
under tight homeostatic control. Inactivating mutations in ATP7B, a P-type Cu
ATPase that functions in copper excretion, promote aberrant accumulation of the
metal, primarily the in liver and brain. This condition underlies Wilson's
disease, a severe autosomal recessive disorder characterized by profound hepatic
and neurological deficits. Current treatment regimens rely on the use of broad
specificity metal chelators as "decoppering" agents; however, there are side
effects that limit their effectiveness. Here, we present the characterization of
DPM-1001 {methyl 4-[7-hydroxy-10,13-dimethyl-3-({4-[(pyridin-2
ylmethyl)amino]butyl}amino)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]
pentanoate} as a potent and highly selective chelator of copper that is orally
bioavailable. Treatment of cell models, including fibroblasts derived from
Wilson's disease patients, eliminated adverse effects associated with copper
accumulation. Furthermore, treatment of the toxic milk mouse model of Wilson's
disease with DPM-1001 lowered the levels of copper in the liver and brain,
removing excess copper by excretion in the feces while ameliorating symptoms
associated with the disease. These data suggest that it may be worthwhile to
investigate DPM-1001 further as a new therapeutic agent for the treatment of
Wilson's disease, with potential for application in other indications associated
with elevated copper, including cancer and neurodegenerative diseases.
PMID- 29945889
TI - Chromosomal analysis in IVF: just how useful is it?
AB - Designed to minimize chances of genetically abnormal embryos, preimplantation
genetic diagnosis (PGD) involves in vitro fertilization (IVF), embryo biopsy,
diagnosis and selective embryo transfer. Preimplantation genetic testing for
aneuploidy (PGT-A) aims to avoid miscarriage and live born trisomic offspring and
to improve IVF success. Diagnostic approaches include fluorescence in situ
hybridization (FISH) and more contemporary comprehensive chromosome screening
(CCS) including array comparative genomic hybridization (aCGH), quantitative
polymerase chain reaction (PCR), next-generation sequencing (NGS) and
karyomapping. NGS has an improved dynamic range, and karyomapping can detect
chromosomal and monogenic disorders simultaneously. Mosaicism (commonplace in
human embryos) can arise by several mechanisms; those arising initially
meiotically (but with a subsequent post-zygotic 'trisomy rescue' event) usually
lead to adverse outcomes, whereas the extent to which mosaics that are initially
chromosomally normal (but then arise purely post-zygotically) can lead to
unaffected live births is uncertain. Polar body (PB) biopsy is the least common
sampling method, having drawbacks including cost and inability to detect any
paternal contribution. Historically, cleavage-stage (blastomere) biopsy has been
the most popular; however, higher abnormality levels, mosaicism and potential for
embryo damage have led to it being superseded by blastocyst (trophectoderm - TE)
biopsy, which provides more cells for analysis. Improved biopsy, diagnosis and
freeze-all strategies collectively have the potential to revolutionize PGT-A, and
there is increasing evidence of their combined efficacy. Nonetheless, PGT-A
continues to attract criticism, prompting questions of when we consider the
evidence base sufficient to justify routine PGT-A? Basic biological research is
essential to address unanswered questions concerning the chromosome complement of
human embryos, and we thus entreat companies, governments and charities to fund
more. This will benefit both IVF patients and prospective parents at risk of
aneuploid offspring following natural conception. The aim of this review is to
appraise the 'state of the art' in terms of PGT-A, including the controversial
areas, and to suggest a practical 'way forward' in terms of future diagnosis and
applied research.
PMID- 29945888
TI - POU2F3 is a master regulator of a tuft cell-like variant of small cell lung
cancer.
AB - Small cell lung cancer (SCLC) is widely considered to be a tumor of pulmonary
neuroendocrine cells; however, a variant form of this disease has been described
that lacks neuroendocrine features. Here, we applied domain-focused CRISPR
screening to human cancer cell lines to identify the transcription factor (TF)
POU2F3 (POU class 2 homeobox 3; also known as SKN-1a/OCT-11) as a powerful
dependency in a subset of SCLC lines. An analysis of human SCLC specimens
revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack
expression of neuroendocrine markers and instead express markers of a
chemosensory lineage known as tuft cells. Using chromatin- and RNA-profiling
experiments, we provide evidence that POU2F3 is a master regulator of tuft cell
identity in a variant form of SCLC. Moreover, we show that most SCLC tumors can
be classified into one of three lineages based on the expression of POU2F3,
ASCL1, or NEUROD1. Our CRISPR screens exposed other unique dependencies in POU2F3
expressing SCLC lines, including the lineage TFs SOX9 and ASCL2 and the receptor
tyrosine kinase IGF1R (insulin-like growth factor 1 receptor). These data reveal
POU2F3 as a cell identity determinant and a dependency in a tuft cell-like
variant of SCLC, which may reflect a previously unrecognized cell of origin or a
trans-differentiation event in this disease.
PMID- 29945890
TI - Loss of IDO1 Expression From Human Pancreatic beta-Cells Precedes Their
Destruction During the Development of Type 1 Diabetes.
AB - Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that
is deficient in patients with type 1 diabetes (T1D). In this study, we present
the first systematic evaluation of IDO1 expression and localization in human
pancreatic tissue. Although IDO1 was constitutively expressed in beta-cells from
donors without diabetes, less IDO1 was expressed in insulin-containing islets
from double autoantibody-positive donors and patients with recent-onset T1D,
although it was virtually absent in insulin-deficient islets from donors with
T1D. Scatter plot analysis suggested that IDO1 decay occurred in individuals with
multiple autoantibodies, prior to beta-cell demise. IDO1 impairment might
therefore contribute to beta-cell demise and could potentially emerge as a
promising therapeutic target.
PMID- 29945891
TI - Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation
Factor 3 in Adipose Tissue Macrophages.
AB - Previous genetic studies in mice have shown that functional loss of activin
receptor-like kinase 7 (ALK7), a type I transforming growth factor-beta receptor,
increases lipolysis to resist fat accumulation in adipocytes. Although
growth/differentiation factor 3 (GDF3) has been suggested to function as a ligand
of ALK7 under nutrient-excess conditions, it is unknown how GDF3 production is
regulated. Here, we show that a physiologically low level of insulin converts
CD11c- adipose tissue macrophages (ATMs) into GDF3-producing CD11c+ macrophages
ex vivo and directs ALK7-dependent accumulation of fat in vivo. Depletion of ATMs
by clodronate upregulates adipose lipases and reduces fat mass in ALK7-intact
obese mice, but not in their ALK7-deficient counterparts. Furthermore, depletion
of ATMs or transplantation of GDF3-deficient bone marrow negates the in vivo
effects of insulin on both lipolysis and fat accumulation in ALK7-intact mice.
The GDF3-ALK7 axis between ATMs and adipocytes represents a previously
unrecognized mechanism by which insulin regulates both fat metabolism and mass.
PMID- 29945892
TI - Gender disparities in screening for congenital hypothyroidism using thyroxine as
a primary screen.
AB - OBJECTIVE: Newborn screening for congenital hypothyroidism (CH) is based on
testing for the markers thyroxine (T4) and/or thyroid-stimulating hormone (TSH).
Diagnosis of CH is complicated because many factors affect the levels of these
hormones including infant birth weight, prematurity and age at specimen
collection. We investigated whether the sex of the newborn affected the levels of
T4 and TSH and consequently the outcome of newborn screening. DESIGN: In New York
State, the Newborn Screening program initially tests all infants for T4 and any
baby with a result in the lowest 10% is triaged for TSH screening. We analyzed
data from 2008 to 2016 to determine mean and median T4 and TSH values and how
these results correlate with the sex of infants who are reported as borderline,
referred and confirmed with CH. METHODS: T4 and TSH concentrations in dried blood
spots were measured using commercially available fluoroimmunoassays. RESULTS:
From 2008 to 2016, of the 2.4 million specimens tested for thyroxine, 51.5% were
from male and 48.5% were from female infants. Male infants constituted 60% of
specimens triaged for TSH testing, 64.9% of repeat requests and 59.6% of
referrals, but only 49% of confirmed CH cases. The mean and median T4 values were
lower (a difference of approximately 0.8-1.1 MUg/dL each year) and the median TSH
values were higher in male compared to female infants. CONCLUSIONS: Natural
differences in thyroid hormone levels in male and female infants leads to male
infants being disproportionately represented in the false-positive category.
PMID- 29945893
TI - Surgical outcomes of a new affordable non-valved glaucoma drainage device and
Ahmed glaucoma valve: comparison in the first year.
AB - BACKGROUND: A new low-cost, indigenously manufactured, non-valved glaucoma
drainage device (GDD) has been introduced and its design is based on the
Baerveldt Glaucoma Device. We aim to demonstrate the efficacy and safety of this
GDD (Aurolab aqueous drainage implant, AADI) vis-a-vis the valved device, Ahmed
glaucoma valve (AGV), in the management of refractory glaucomas. DESIGN:
Retrospective, comparative, interventional. PARTICIPANTS: Case review of
consecutive patients who underwent GDD surgery by a single fellowship-trained
surgeon at a Tertiary Centre between January 2014 and November 2016. PRIMARY
OUTCOME MEASURE: Intraocular pressure (IOP). SECONDARY: Antiglaucoma medication
(AGM), LogMAR best-corrected visual acuity (BCVA), complications. RESULTS: A
total of 88 eyes of 83 patients were included; 36 eyes received AGV and 52 AADI.
Preoperative parameters were similar between groups. Median follow-up was 13 and
12 months for AADI and AGV, respectively. Overall success rate was higher in AADI
(92.3%) vs AGV (80.5%) (p<0.001). The median IOP in mm Hg (Quartiles; IQR) (AADI
14 (10,15;5) vs AGV 16 (14,20;6)) and AGM (AADI: 0 (0,1;1) vs AGV 2
(1,2.75;1.75)) was significantly lower in the AADI group at last follow-up
(p<0.001). LogMAR BCVA improved in both groups; complication rates (AADI 44.2% vs
AGV 52.7%) were comparable (p=0.59). CONCLUSIONS: Both procedures were effective
in reduction of IOP and need for AGM. Nevertheless, overall success rate was
higher in the AADI group and IOP and number of AGM required was significantly
lower in the AADI group; this affordable GDD could have a tremendous impact in
the management of refractory glaucomas in low-income to middle-income countries.
PMID- 29945886
TI - Molecular mechanisms of the preventable causes of cancer in the United States.
AB - Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer
deaths in the United States alone. The public health burden associated with these
numbers has motivated enormous research efforts into understanding the root
causes of cancer. These efforts have led to the recognition that between 40% and
45% of cancers are associated with preventable risk factors and, importantly,
have identified specific molecular mechanisms by which these exposures modify
human physiology to induce or promote cancer. The increasingly refined knowledge
of these mechanisms, which we summarize here, emphasizes the need for greater
efforts toward primary cancer prevention through mitigation of modifiable risk
factors. It also suggests exploitable avenues for improved secondary prevention
(which includes the development of therapeutics designed for cancer interception
and enhanced techniques for noninvasive screening and early detection) based on
detailed knowledge of early neoplastic pathobiology. Such efforts would
complement the current emphasis on the development of therapeutic approaches to
treat established cancers and are likely to result in far greater gains in
reducing morbidity and mortality.
PMID- 29945894
TI - Functional and aesthetic outcomes of eyelid skin grafting in facial nerve palsy.
AB - AIM: To report the functional and aesthetic outcomes of eyelid full-thickness
skin grafting (FTSG) in patients with facial nerve palsy (FNP). METHODS: This is
a retrospective, non-comparative, single-centre review of all patients with FNP
who underwent FTSG over an 8-year period. Functional outcomes were collected
through case notes review: CADS (cornea, static asymmetry and dynamic and
synkinesis) score facial nerve grading and lagophthalmos on blink, gentle and
forced closure. Marginal reflex distance (MRD1 and MRD2) was calculated on
standardised photographs. The aesthetic outcomes were assessed objectively by two
blinded independent assessors who assessed standardised photographs based on a
mutually agreed grading scale. Both functional and aesthetic outcomes were
measured preoperatively, and at early (1-3 months), intermediate (3-6 months) and
late (>9 months) postoperative periods. RESULTS: A total of 28 eyelid FTSGs were
performed on 21 patients (11 female, 10 male) between 2008 and 2016. The mean age
was 68 (range, 16-89) years and the mean follow-up was 20.8 (range, 12-30)
months. The CADS score (cornea (p<0.001), static asymmetry (p<0.001), dynamic
function (p<0.001)), MRD2 (p=0.002) and lagophthalmos (blink (p=0.003), gentle
(p<0.001), forced (p=0.003)) improved through early and late postoperative
periods. Aesthetically, the grafts appeared to look natural in terms of colour,
surface contour and graft edge from the intermediate postoperative period and
continued to improve significantly by the late postoperative period. CONCLUSION:
The use of periocular FTSG is effective in improving lagophthalmos and
periorbital symmetry in patients with FNP where skin contraction exists. They
should be considered as an adjunct to other oculoplastic procedures for both
functional and aesthetic rehabilitation.
PMID- 29945895
TI - Prevalence of refractive errors in Colombia: MIOPUR study.
AB - PURPOSE: To determine the prevalence of refractive errors in Colombia and its
relations with demographic and socioeconomic variables. METHODS: A cross
sectional study performed in 10 Colombian administrative districts (MIOPUR
study), including children and adolescents from 8 to 17 years old and adults from
35 to 55 years old. RESULTS: 3608 individuals (100% of whom agreed to
participate) were included. Prevalence estimates of refractive errors were:
hyperopia 32.3% (95% CI 30.7 to 33.8), myopia 12.9% (95% CI 11.8 to 14.0), mixed
astigmatism 2.8% (95% CI 2.2 to 3.3) and anisometropia 1.9% (95% CI 1.4 to 2.3).
Prevalence of myopia in 15-year-old adolescents was 14.7%. In children and
adolescents, the hyperopia prevalence decreased while myopia prevalence increased
with age. In the adults group, the tendency was the contrary. Myopia prevalence
reached 15.7% in urban and 9.2% in rural areas, and for hyperopia, the rates were
29.4% in urban and 36.1% in rural areas. In the multivariate analysis, living in
an urban area significantly increased the risk of having myopia (OR: 1.45 (1.12
to 1.89); p<0.01). There were significant regional differences among diverse
zones of the country. CONCLUSIONS: Prevalence estimates of myopia and hyperopia
in Colombia were found to be at an intermediate point compared with global data.
In adults, myopia frequency was lower than in European and Asian studies. The
prevalence of myopia increased during childhood and adolescence and was higher in
middle-aged adults (35-39 years) than in older adults. On the other hand,
hyperopia rates increased with age, findings that suggest a cohort effect. In the
multivariate analysis, residence in urban areas and living in a medium-high
socioeconomic status were linked to myopia.
PMID- 29945896
TI - Premacular membrane formation after scleral buckling for primary rhegmatogenous
retinal detachment: prospective study and pathophysiological insights.
AB - PURPOSE: To investigate the incidence, clinical features and risk factors of
premacular membrane (PMM) formation after primary rhegmatogenous retinal
detachment (RRD) repair with scleral buckling (SB) alone. METHODS: This
institutional, prospective and consecutive case series included phakic eyes with
RRD, treated with SB alone within 7 days from the occurrence of symptoms, with a
follow-up of 6 months. Spectral-domain optical coherence tomography images were
reviewed. The association of PMM development and morphology with preoperative and
intraoperative RRD features was analysed. RESULTS: Ninety-two patients with a
mean age of 56+/-13 years completed the 6 months follow-up period.
Postoperatively, eyes with any PMM stage were 30 out of 92 (32.6%) at 1 month and
47 out of 92 (51,1%) at both 3 months and 6 months. Over the follow-up period, 17
out of 47 PMMs (36.2%) progressed to later stages. Progression of PMMs to later
stages were observed only in RRDs involving the macular region (17 out of 35
eyes, 48.5%), while none of the PMMs in macula-sparing detachments progressed to
later stages (p=0.020). The risk factors significantly associated with
postoperative new onset of PMM were preoperative RRDs involving the macular
region (p=0.001), cryopexy time (p=0.045), presence of horseshoe tears (p=0.003),
worse preoperative visual acuity (p=0.004) and subretinal fluid drainage
(p=0.047). CONCLUSION: The incidence of postoperative PMM formation after RRD
repair with SB alone was high. In retinal detachments involving the macular
region PMM were more severe, tending to anatomical progression and functional
deterioration. Activation of foveal Muller cell in detachments involving the
macula may be a key factor in PMM progression.
PMID- 29945897
TI - Correction to "Agonist-Dependent and-Independent kappa Opioid Receptor
Phosphorylation: Distinct Phosphorylation Patterns and Different Cellular
Outcomes".
PMID- 29945900
TI - Adverse Neuropsychiatric Events and Recreational Use of Efavirenz and Other HIV-1
Antiretroviral Drugs.
AB - Efavirenz is a highly effective HIV-1 antiretroviral; however, it is also
frequently associated with neuropsychiatric adverse events (NPAE) that include
abnormal dreams, sleep disturbances, nervousness, anxiety, depression, and
dizziness. The incidence of NPAEs upon initiation of treatment with efavirenz
containing medications is high, exceeding 50% in most studies. Although the NPAEs
tend to decrease after the first month in many patients, they persist for long
periods of time in others. Efavirenz-based treatment is generally well-tolerated
in children, although some experience persistent concentration problems, as well
as sleep disturbances, psychotic reactions, and seizures. In an effort to link
basic with clinical research, parameters associated with efavirenz brain exposure
are discussed, and factors that increase efavirenz levels are explored in depth
as they are expected to contribute to NPAE risk. These include the role of
modifiable and nonmodifiable risk factors such as diet, weight, and drug-drug
interactions and sex, age, and ethnicity/pharmacogenetics. In addition to NPAEs,
this review explores what is known about antiretroviral (ARV) drugs being used
for recreational purposes. Although multiple ARV drugs are covered, special
attention is devoted to efavirenz given that the majority of reports of NPAEs and
illicit use of ARV drugs concern efavirenz. The evolving molecular mechanistic
basis of NPAEs and abuse of efavirenz point to a complex and polymodal receptor
pharmacology. Animal studies to date primarily point to a serotonergic mechanism
of action. Recently emerging associations between HIV-associated neurocognitive
disorder and efavirenz use, and possible contributions of the mitochondrial
immune-inflammatory-redox cascade are explored in the context of the signaling
mechanisms that appear to be involved.
PMID- 29945902
TI - BMA responds to racism in the NHS.
PMID- 29945901
TI - Tubular Excretory Canal Structure Depends on Intermediate Filaments EXC-2 and IFA
4 in Caenorhabditis elegans.
AB - The excretory canals of Caenorhabditis elegans are a model for understanding the
maintenance of apical morphology in narrow single-celled tubes. Light and
electron microscopy shows that mutants in exc-2 start to form canals normally,
but these swell to develop large fluid-filled cysts that lack a complete terminal
web at the apical surface, and accumulate filamentous material in the canal
lumen. Here, whole-genome sequencing and gene rescue show that exc-2 encodes
intermediate filament protein IFC-2 EXC-2/IFC-2 protein, fluorescently tagged via
clustered regularly interspaced short palindromic repeats/Cas9, is located at the
apical surface of the canals independently of other intermediate filament
proteins. EXC-2 is also located in several other tissues, though the tagged
isoforms are not seen in the larger intestinal tube. Tagged EXC-2 binds via
pulldown to intermediate filament protein IFA-4, which is also shown to line the
canal apical surface. Overexpression of either protein results in narrow but
shortened canals. These results are consistent with a model whereby three
intermediate filaments in the canals-EXC-2, IFA-4, and IFB-1-restrain swelling of
narrow tubules in concert with actin filaments that guide the extension and
direction of tubule outgrowth, while allowing the tube to bend as the animal
moves.
PMID- 29945899
TI - Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications
for Addiction Treatment Development.
AB - Although the last 50 years of clinical and preclinical research have demonstrated
that addiction is a brain disease, we still have no neural circuit-based
treatments for substance dependence or cue reactivity at large. Now, for the
first time, it appears that a noninvasive brain stimulation technique known as
transcranial magnetic stimulation (TMS), which is Food and Drug Administration
approved to treat depression, may be the first tool available to fill this
critical void in addiction treatment development. The goals of this review are to
1) introduce TMS as a tool to induce causal change in behavior, cortical
excitability, and frontal-striatal activity; 2) describe repetitive TMS (rTMS) as
an interventional tool; 3) provide an overview of the studies that have evaluated
rTMS as a therapeutic tool for alcohol and drug use disorders; and 4) outline a
conceptual framework for target selection when designing future rTMS clinical
trials in substance use disorders. The manuscript concludes with some suggestions
for methodological innovation, specifically with regard to combining rTMS with
pharmacotherapy as well as cognitive behavioral training paradigms. We have
attempted to create a comprehensive manuscript that provides the reader with a
basic set of knowledge and an introduction to the primary experimental questions
that will likely drive the field of TMS treatment development forward for the
next several years.
PMID- 29945903
TI - Actin filaments partition primary cilia membranes into distinct fluid corrals.
AB - Physical properties of primary cilia membranes in living cells were examined
using two independent, high-spatiotemporal-resolution approaches: fast tracking
of single quantum dot-labeled G protein-coupled receptors and a novel two-photon
super-resolution fluorescence recovery after photobleaching of protein ensemble.
Both approaches demonstrated the cilium membrane to be partitioned into corralled
domains spanning 274 +/- 20 nm, within which the receptors are transiently
confined for 0.71 +/- 0.09 s. The mean membrane diffusion coefficient within the
corrals, Dm1 = 2.9 +/- 0.41 um2/s, showed that the ciliary membranes were among
the most fluid encountered. At longer times, the apparent membrane diffusion
coefficient, Dm2 = 0.23 +/- 0.05 um2/s, showed that corral boundaries impeded
receptor diffusion 13-fold. Mathematical simulations predict the probability of G
protein-coupled receptors crossing corral boundaries to be 1 in 472. Remarkably,
latrunculin A, cytochalasin D, and jasplakinolide treatments altered the corral
permeability. Ciliary membranes are thus partitioned into highly fluid membrane
nanodomains that are delimited by filamentous actin.
PMID- 29945904
TI - Actin polymerization controls cilia-mediated signaling.
AB - Primary cilia are polarized organelles that allow detection of extracellular
signals such as Hedgehog (Hh). How the cytoskeleton supporting the cilium
generates and maintains a structure that finely tunes cellular response remains
unclear. Here, we find that regulation of actin polymerization controls primary
cilia and Hh signaling. Disrupting actin polymerization, or knockdown of N
WASp/Arp3, increases ciliation frequency, axoneme length, and Hh signaling.
Cdc42, a potent actin regulator, recruits both atypical protein pinase C
iota/lambda (aPKC) and Missing-in-Metastasis (MIM) to the basal body to maintain
actin polymerization and restrict axoneme length. Transcriptome analysis
implicates the Src pathway as a major aPKC effector. aPKC promotes whereas MIM
antagonizes Src activity to maintain proper levels of primary cilia, actin
polymerization, and Hh signaling. Hh pathway activation requires Smoothened-, Gli
, and Gli1-specific activation by aPKC. Surprisingly, longer axonemes can amplify
Hh signaling, except when aPKC is disrupted, reinforcing the importance of the
Cdc42-aPKC-Gli axis in actin-dependent regulation of primary cilia signaling.
PMID- 29945905
TI - Noninvasive Ventilation as an Important Adjunct to an Exercise Training Program
in Subjects With Moderate to Severe COPD.
AB - BACKGROUND: The primary objective of this study was to investigate whether
noninvasive ventilation (NIV) can positively affect exercise capacity, maximum
oxygen uptake (VO2 ), and symptoms after a 6-week physical training program for
subjects with moderate to very severe COPD. METHODS: 47 subjects with COPD who
were enrolled in a physical training program were randomized to either physical
training alone or NIV + physical training (NIV-Physical training). Physical
training consisted of dynamic aerobic exercises on a treadmill 3 times/week for 6
weeks, for a total of 18 sessions. NIV was titrated according to the subject's
tolerance at rest and during exercise. Assessments included physiological
responses and symptoms at the incremental cardiopulmonary exercise test peak and
during submaximal exercise on a treadmill, 6-min walk distance, maximum
inspiratory (PImax) and expiratory pressure (PEmax), BODE index, and health
related quality of life. RESULTS: 43 subjects completed the 6-week physical
training program. Both groups improved 6-min walk distance, PImax, BODE index,
and quality of life, and no differences were found between groups. However,
significant improvements were observed for subjects in the NIV-Physical training
group with regard to PEmax, maximum VO2 , maximum metabolic equivalents,
circulatory power, and maximum SpO2 . CONCLUSIONS: A 6-week physical training
program alone can improve tolerance for exercise and quality of life, in addition
to reducing the risk of mortality. However, NIV associated with a physical
training program was shown to have an additive beneficial effect on powerful
prognostic markers (maximum VO2 and circulatory power) and to reduce symptoms and
improve oxygen saturation in subjects with moderate to very severe COPD.
PMID- 29945906
TI - Predictive Value of STOP-BANG on OSAS-Related Complications Following Coronary
Artery Bypass Grafting.
AB - BACKGROUND: The time and conditions may not be suitable for performing
polysomnography (PSG) before urgent or emergent surgeries, for example, a
coronary artery bypass graft. Unavailability in many centers, critical clinical
situation, and inability to arrange a timely scheduled appointment are other
limitations for PSG. In this study, we aimed to investigate if the STOP-BANG
Questionnaire may predict obstructive sleep apnea syndrome (OSAS) related
postoperative pulmonary alterations during coronary artery surgery. METHODS:
Sixty-one subjects who were scheduled to undergo elective isolated coronary
artery bypass graft surgery and were consulted for preoperative pulmonary
assessment were recruited to the study. The STOP-BANG Questionnaire was used with
the subjects; then their relationship with postoperative complications was
assessed. RESULTS: Results of the STOP-BANG Questionnaire revealed that 36.1% of
subjects were at high risk for OSAS. Three groups were established according to
the STOP-BANG Questionnaire (low risk, group 1; moderate risk, group 2; high
risk, group 3) and study parameters, including PEEP value in ventilator,
detection of apnea at ventilator, CPAP time after extubation, SpO2 1 h after
extubation, postoperative hypoxemia, need for CPAP, and ICU length of stay
revealed significant relationships among these groups. CONCLUSIONS: The STOP-BANG
Questionnaire may predict the OSAS risk and OSAS-related pulmonary complications
for patients who are candidates for a coronary artery bypass graft and unable to
be evaluated with PSG before surgery due to technical or time-related
limitations.
PMID- 29945907
TI - Stress Index Can Be Accurately and Reliably Assessed by Visually Inspecting
Ventilator Waveforms.
AB - BACKGROUND: Stress index provides a noninvasive approach to detect injurious
ventilation patterns and to personalize ventilator settings. Obtaining the stress
index (SI), however, requires quantitatively analyzing the shape of pressure-time
curve with dedicated instruments or a specific ventilator, which may encumber its
clinical implementation. We hypothesized that the SI could be qualitatively
determined through a visual inspection of ventilator waveforms. METHODS: Thirty
six adult subjects undergoing volume controlled ventilation without spontaneous
breathing were enrolled. For each subject, 2 trained clinicians visually
inspected the pressure-time curve directly from the ventilator screen. They then
qualitatively categorized the shape of pressure-time curve as linear, a downward
concavity, or an upward concavity at the bedside. We simultaneously recorded
airway pressure and flow signals using a dedicated instrument. A quantitative off
line analysis was performed to calculate the SI using specific research software.
This quantitative analysis of the SI served as the reference method for
classifying the shape of the pressure-time curve (ie, linear, a downward
concavity, or an upward concavity). We compared the SI categorized by visual
inspection with that by the reference. RESULTS: We obtained 200 SI assessments of
pressure-time curves, among which 125 (63%) were linear, 55 (27%) were a downward
concavity, and 20 (10%) were an upward concavity as determined by the reference
method. The overall accuracy of visual inspection and weighted kappa statistic
(95% CI) was 93% (88-96%) and 0.88 (0.82-0.94), respectively. The sensitivity and
specificity to distinguish a downward concavity from a linear shape were 91% and
98%, respectively. The respective sensitivity and specificity to distinguish an
upward concavity from a linear shape were 95% and 95%. CONCLUSIONS: Visual
inspection of the pressure-time curve on the ventilator screen is a simple and
reliable approach to assess SI at the bedside. This simplification may facilitate
the implementation of SI in clinical practice to personalize mechanical
ventilation. (ClinicalTrials.gov registration NCT03096106.).
PMID- 29945908
TI - Accuracy of Delivery and Effects on Absolute Humidity of Low Tidal Volume by ICU
Ventilators.
AB - BACKGROUND: During extracorporeal membrane oxygenation for ARDS, a range of 1-4
mL/kg predicted body weight tidal volume (VT) is commonly used. We explored
whether such a low VT could be adequately delivered by ICU ventilators, and
whether such low VTs prevent the heated humidifier (HH) from reaching the
recommended target of 33 mg/L absolute humidity (AH). METHODS: We attached a lung
model to 5 ICU ventilators set in volume controlled mode and body temperature and
pressure saturated. We ran 2 protocols over a 100-280 mL VT range used with adult
or neonatal breathing circuit at a breathing frequency (f) of 15 (f15) or 30
(f30) breaths/min. In the first protocol, with the HH off, VT was measured with a
dedicated data logger and expressed in body temperature and pressure saturated.
The relationships of measured VT to set VT were studied, and the relative error
in VT was analyzed within its 10% boundaries. In the second protocol, the HH was
on, and we measured AH using a psychrometric method. The relationship of AH to
set VT was analyzed with linear regression. RESULTS: For the 5 ventilators used,
the slope (95% CI) between measured VT versus set VT averaged 0.93 (0.92-0.93),
0.93 (0.93-0.94), 0.91 (0.90-0.91), and 0.91 (0.90-0.91) mL/mL for adult and
neonatal circuits at f15 and f30, respectively (P < .05 vs 1 in each instance),
indicating a systematic under-delivery of VT. The VT relative error fell within
the +/-10% accuracy range for only 2 ventilators with adult circuits at f15 and
f30. AH increased linearly with VT. The recommended target of 33 mg/L AH was
reached with all of the ventilators for the adult circuit at f30 only. The
minimum volume that met the recommended threshold for AH was 100, 150, 190, 160,
and 100 mL for the G5, Carestation, PB980, Servo-U, and V500 ventilators,
respectively, at f30. CONCLUSION: Low VT was systematically under-delivered by
modern ICU ventilators by roughly 7-9%. To meet the recommended target of 33 mg/L
AH, adult circuit at f30 should be used.
PMID- 29945909
TI - Short- and Long-Term Reliability of the 6-Minute Walk Test in People With
Idiopathic Pulmonary Fibrosis.
AB - BACKGROUND: The aim of this work was to investigate the short- and long-term test
retest reliability of the 6-min walk distance (6MWD), peak heart rate, and nadir
oxygen desaturation in idiopathic pulmonary fibrosis (IPF). METHODS: A
reliability study of 70 adults with IPF was undertaken within out-patient
pulmonary rehabilitation programs at 2 tertiary hospitals. Participants completed
2 baseline 6-min walk tests using a standard protocol, with continuous measures
of percutaneous SpO2 and heart rate via pulse oximetry. The 6-min walk test was
completed immediately following an intervention period and 6 months after.
Reproducibility was assessed by intraclass correlation coefficient and Bland
Altman analysis. RESULTS: Participants with a mean +/- SD diffusing capacity of
the lung for carbon monoxide of 48 +/- 14% were included. The reliability of the
6MWD was high (intraclass correlation coefficient = 0.96) with a mean learning
effect of 21 m (95% CI 12-30 m). The learning effect persisted at 8 weeks (mean
14 m, 95% CI 5-23 m) but not 6 months (mean 15 m, 95% CI -1 to 30 m). Using the
best (greatest) 6MWD significantly reduced the proportion of participants who
were classified as having a clinically important response to rehabilitation
compared with using the first 6MWD (40% vs 54%, P = .002). Nadir SpO2 was
reproducible, with a mean difference of 0.7 +/- 2.2%, and limits of agreement of
4 to 5%. Peak heart rate was more variable, with mean difference 5 +/- 9
beats/min and limits of agreement of -12 to 20 beats/min. CONCLUSIONS: The 6MWD
is a reproducible measure of exercise capacity in people with IPF. Whereas the
nadir SpO2 may be accurately determined from one test, evaluating change in 6MWD
with interventions may require 2 tests on each occasion. (ClinicalTrials.gov
registration NCT0016828.).
PMID- 29945910
TI - Effects of High-Flow Nasal Cannula on End-Expiratory Lung Impedance in Semi
Seated Healthy Subjects.
AB - BACKGROUND: High-flow nasal cannula (HFNC) enables delivery of humidified gas at
high flow while controlling the FIO2 . Although its use is growing in patients
with acute respiratory failure, little is known about the impact of HFNC on lung
volume. Therefore, we aimed to assess lung volume changes in healthy subjects at
different flows and positions. METHODS: This was a prospective physiological
study performed in 16 healthy subjects. The changes in lung volumes were assessed
by measuring end-expiratory lung impedance by using electrical impedance
tomography. All the subjects successively breathed during 5 min in these
following conditions: while in a supine position without HFNC (T0) and 3
measurements in a semi-seated position at 45 degrees without HFNC (T1), and with
HFNC at a flow of 30 L/min (T2), and 50 L/min (T3). RESULTS: Compared with the
supine position, the values of end-expiratory lung impedance significantly
increased with the subjects in a semi-seated position. End-expiratory lung
impedance significantly increased after HFNC initiation in subjects in a semi
seated position and further increased by increasing flow at 50 L/min. When taking
the end-expiratory lung impedance measurement in subjects in a semi-seated
position (T1) as reference, the differences among the medians of global end
expiratory lung impedance were statistically significant (P < .001), which
amounted to 1.05 units in T1; 1.12 units in T2; and 1.44 units in T3 (P < .05 for
all comparisons, Wilcoxon test). The breathing frequency did not differ between
the supine and semi-seated position (T0 and T1) but significantly decreased after
initiation of HFNC and further decreased at high flow. T0 and T1 were not
different (P = .13); whereas there was a statistically significant difference
among T1, T2, and T3 (P < .05, post hoc test with Bonferroni correction).
CONCLUSIONS: In healthy subjects, the semi-seated position and the use of HFNC
increased end-expiratory lung impedance globally. These changes were accompanied
by a significant decrease in the breathing frequency.
PMID- 29945898
TI - Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic
Mechanisms.
AB - Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, has been in
clinical use since 1970. Although best characterized for its dissociative
anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and
antidepressant actions. We provide a comprehensive review of these therapeutic
uses, emphasizing drug dose, route of administration, and the time course of
these effects. Dissociative, psychotomimetic, cognitive, and peripheral side
effects associated with short-term or prolonged exposure, as well as recreational
ketamine use, are also discussed. We further describe ketamine's
pharmacokinetics, including its rapid and extensive metabolism to norketamine,
dehydronorketamine, hydroxyketamine, and hydroxynorketamine (HNK) metabolites.
Whereas the anesthetic and analgesic properties of ketamine are generally
attributed to direct ketamine-induced inhibition of N-methyl-D-aspartate
receptors, other putative lower-affinity pharmacological targets of ketamine
include, but are not limited to, gamma-amynobutyric acid (GABA), dopamine,
serotonin, sigma, opioid, and cholinergic receptors, as well as voltage-gated
sodium and hyperpolarization-activated cyclic nucleotide-gated channels. We
examine the evidence supporting the relevance of these targets of ketamine and
its metabolites to the clinical effects of the drug. Ketamine metabolites may
have broader clinical relevance than was previously considered, given that HNK
metabolites have antidepressant efficacy in preclinical studies. Overall,
pharmacological target deconvolution of ketamine and its metabolites will provide
insight critical to the development of new pharmacotherapies that possess the
desirable clinical effects of ketamine, but limit undesirable side effects.
PMID- 29945911
TI - Carboxyl-Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy
by Suppressing the Protein Kinase B Signaling Pathway.
AB - BACKGROUND: Carboxyl-terminal modulator protein (CTMP) has been implicated in
cancer, brain injury, and obesity. However, the role of CTMP in pathological
cardiac hypertrophy has not been identified. METHODS AND RESULTS: In this study,
decreased expression of CTMP was observed in both human failing hearts and murine
hypertrophied hearts. To further explore the potential involvement of CTMP in
pathological cardiac hypertrophy, cardiac-specific CTMP knockout and
overexpression mice were generated. In vivo experiments revealed that CTMP
deficiency exacerbated the cardiac hypertrophy, fibrosis, and function induced by
pressure overload, whereas CTMP overexpression alleviated the response to
hypertrophic stimuli. Consistent with the in vivo results, adenovirus-mediated
gain-of-function or loss-of-function experiments showed that CTMP also exerted a
protective effect against hypertrophic responses to angiotensin II in vitro.
Mechanistically, CTMP ameliorated pathological cardiac hypertrophy through the
blockade of the protein kinase B signaling pathway. Moreover, inhibition of
protein kinase B activation with LY294002 rescued the deteriorated effect in
aortic banding-treated cardiac-specific CTMP knockout mice. CONCLUSIONS: Taken
together, these findings imply, for the first time, that increasing the cardiac
expression of CTMP may be a novel therapeutic strategy for pathological cardiac
hypertrophy.
PMID- 29945912
TI - Inhibition of MicroRNA-155 Supports Endothelial Tight Junction Integrity
Following Oxygen-Glucose Deprivation.
AB - BACKGROUND: Brain microvascular endothelial cells form a highly selective blood
brain barrier regulated by the endothelial tight junctions. Cerebral ischemia
selectively targets tight junction protein complexes, which leads to significant
damage to cerebral microvasculature. Short noncoding molecules called microRNAs
are implicated in the regulation of various pathological states, including
endothelial barrier dysfunction. In the present study, we investigated the
influence of microRNA-155 (miR-155) on the barrier characteristics of human
primary brain microvascular endothelial cells (HBMECs). METHODS AND RESULTS:
Oxygen-glucose deprivation was used as an in vitro model of ischemic stroke.
HBMECs were subjected to 3 hours of oxygen-glucose deprivation, followed by
transfections with miR-155 inhibitor, mimic, or appropriate control
oligonucleotides. Intact normoxia control HBMECs and 4 oxygen-glucose deprivation
treated groups of cells transfected with appropriate nucleotide were subjected to
endothelial monolayer electrical resistance and permeability assays, cell
viability assay, assessment of NO and human cytokine/chemokine release,
immunofluorescence microscopy, Western blot, and polymerase chain reaction
analyses. Assessment of endothelial resistance and permeability demonstrated that
miR-155 inhibition improved HBMECs monolayer integrity. In addition, miR-155
inhibition significantly increased the levels of major tight junction proteins
claudin-1 and zonula occludens protein-1, while its overexpression reduced these
levels. Immunoprecipitation and colocalization analyses detected that miR-155
inhibition supported the association between zonula occludens protein-1 and
claudin-1 and their stabilization at the HBMEC membrane. Luciferase reporter
assay verified that claudin-1 is directly targeted by miR-155. CONCLUSIONS: Based
on these results, we conclude that miR-155 inhibition-induced strengthening of
endothelial tight junctions after oxygen-glucose deprivation is mediated via its
direct target protein claudin-1.
PMID- 29945913
TI - High Burden of 30-Day Readmissions After Acute Venous Thromboembolism in the
United States.
AB - BACKGROUND: Venous thromboembolism (VTE) is the third leading cause of vascular
disease and accounts for $10 billion in annual US healthcare costs. The
nationwide burden of 30-day readmissions after such events has not been
comprehensively assessed. METHODS AND RESULTS: We analyzed adults >=18 years of
age with hospitalizations associated with acute VTE between January 1, 2010, and
December 31, 2014, in the Nationwide Readmissions Database. International
Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes
were used to identify hospitalizations associated with acute pulmonary embolism
or deep vein thrombosis. The primary outcome was the rate of unplanned 30-day
readmission. Hierarchical logistic regression was used to calculate hospital
specific 30-day risk-standardized readmission rates, a marker of healthcare
quality. Among 1 176 335 hospitalizations with acute VTE, in-hospital death
occurred in 6.2%. VTE was associated with malignancy in 19.7%, recent surgery in
19.3%, recent trauma in 4.6%, hypercoagulability in 3.3%, and pregnancy in 1.0%.
Among survivors to discharge, the 30-day readmission rate was 17.5%, with no
significant difference in rates across study years (17.4%-17.7%; P=0.10 for
trend). Major predictors of readmission were malignancy (relative risk, 1.49, 95%
confidence interval 1.47-1.50), Medicaid insurance (relative risk, 1.48, 95%
confidence interval 1.46-1.50), and nonelective index admission (relative risk,
1.31, 95% confidence interval 1.29-1.33). Top causes of readmission included
sepsis (9.6%) and procedural complications (8.1%). Median rehospitalization costs
were $9781.7 (interquartile range, $5430.7-$18 784.1), and 8.1% died during
readmission. The interquartile range in risk-standardized readmission rates was
16.6% to 18.3%, suggesting modest interhospital heterogeneity in readmission
risk. CONCLUSIONS: Nearly 1 in 5 patients with acute VTE were readmitted within
30 days. Predictors and causes of readmission were primarily related to patient
characteristics and complications from comorbid conditions, whereas healthcare
quality had a moderate impact on readmission risk.
PMID- 29945914
TI - An Algorithm Based on Deep Learning for Predicting In-Hospital Cardiac Arrest.
AB - BACKGROUND: In-hospital cardiac arrest is a major burden to public health, which
affects patient safety. Although traditional track-and-trigger systems are used
to predict cardiac arrest early, they have limitations, with low sensitivity and
high false-alarm rates. We propose a deep learning-based early warning system
that shows higher performance than the existing track-and-trigger systems.
METHODS AND RESULTS: This retrospective cohort study reviewed patients who were
admitted to 2 hospitals from June 2010 to July 2017. A total of 52 131 patients
were included. Specifically, a recurrent neural network was trained using data
from June 2010 to January 2017. The result was tested using the data from
February to July 2017. The primary outcome was cardiac arrest, and the secondary
outcome was death without attempted resuscitation. As comparative measures, we
used the area under the receiver operating characteristic curve (AUROC), the area
under the precision-recall curve (AUPRC), and the net reclassification index.
Furthermore, we evaluated sensitivity while varying the number of alarms. The
deep learning-based early warning system (AUROC: 0.850; AUPRC: 0.044)
significantly outperformed a modified early warning score (AUROC: 0.603; AUPRC:
0.003), a random forest algorithm (AUROC: 0.780; AUPRC: 0.014), and logistic
regression (AUROC: 0.613; AUPRC: 0.007). Furthermore, the deep learning-based
early warning system reduced the number of alarms by 82.2%, 13.5%, and 42.1%
compared with the modified early warning system, random forest, and logistic
regression, respectively, at the same sensitivity. CONCLUSIONS: An algorithm
based on deep learning had high sensitivity and a low false-alarm rate for
detection of patients with cardiac arrest in the multicenter study.
PMID- 29945915
TI - Linoleic Acid in Adipose Tissue and Development of Ischemic Stroke: A Danish Case
Cohort Study.
AB - BACKGROUND: We investigated the association between the content of linoleic acid
in adipose tissue, a biomarker of long-term intake of linoleic acid, and the risk
of ischemic stroke and its subtypes. METHODS AND RESULTS: The Danish cohort study
Diet, Cancer and Health included 57 053 patients aged 50 to 65 years at
enrollment. All participants had an adipose tissue biopsy performed at
enrollment, while information on ischemic stroke during follow-up was obtained
from the Danish National Patient Register. Stroke diagnoses were all validated
and classified according to the Trial of Org 10172 in Acute Stroke Treatment
(TOAST) classification. Cases and a randomly drawn subcohort of 3500 patients had
their fatty acid composition in adipose tissue determined by gas chromatography.
Hazard ratios with 95% confidence intervals were calculated using weighted Cox
proportional hazard regression. During 13.5 years of follow-up, 1879 ischemic
stroke cases were identified, for which 1755 adipose biopsies were available,
while adipose biopsies were available for 3203 participants in the subcohort.
When comparing the highest and the lowest quartiles of adipose tissue content of
linoleic acid there was a negative association with the rate of total ischemic
stroke (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93) and large artery
atherosclerosis (hazard ratio, 0.61; 95% confidence interval, 0.43-0.88), while
there was an indication of a negative association with small-vessel occlusion
(hazard ratio, 0.87; 95% confidence interval, 0.69-1.11). There was no clear
association with the rate of cardioembolism. CONCLUSIONS: The content of linoleic
acid in adipose tissue was inversely associated with the risk of total ischemic
stroke and stroke caused by large artery atherosclerosis.
PMID- 29945916
TI - Equations for Estimating the Predissected Diameter of the Descending Aorta From
Computed Tomographic Images at the Onset of Aortic Dissection.
AB - BACKGROUND: Estimation of the predissected descending aortic diameter is
important for deciding on the size of a stent graft in cases of acute aortic
dissection. However, no equations for estimating this diameter have been
previously reported. METHODS AND RESULTS: We developed and validated new
equations by investigating computed tomography images that were scanned within 3
years before dissection and those that were scanned immediately after the onset
of dissection. Among 1127 patients with acute aortic dissection (425 type A and
702 type B), 36 were matched for the study from October 2005 to March 2017 at 4
centers. New equations were developed in 17 patients and validated in 19
patients. We measured the predissected whole circumference length (CL) and
postdissected whole CL, true lumen CL, the major diameter, and the minor diameter
of the acutely dissected aorta, followed by calculation of (post-trueCL+post
wholeCL)/2 and (post-major diameter+post-minor diameter)/2. Six equations (linear
function) and modified equations were derived from each of the above-mentioned
parameters. In the derivation sets, equations that used the parameter of (post
trueCL+post-wholeCL)/2 were strongly correlated with pre-wholeCL
(Y=0.9433x+5.0147; R2=0.9001) and showed significantly less bias compared with
the other 5 equations (P<0.0001). In validation sets using this equation, the
mean bias of the circumference length and diameter was 2.7+/-2.8 and 0.85+/-0.89
mm, respectively. A total of 99.2% of the calculated values were within 3 mm in
diameter or less. CONCLUSIONS: Our newly developed equations can be used to
calculate the predissected aortic diameter in cases of acute aortic dissection
and might help to decide the size of the stent graft.
PMID- 29945917
TI - Increased Left Ventricular Mass Index Is Associated With Compromised White Matter
Microstructure Among Older Adults.
AB - BACKGROUND: Left ventricular (LV) hypertrophy is associated with cerebrovascular
disease and cognitive decline. Increased LV mass index is a subclinical imaging
marker that precedes overt LV hypertrophy. This study relates LV mass index to
white matter microstructure and cognition among older adults with normal
cognition and mild cognitive impairment. METHODS AND RESULTS: Vanderbilt Memory &
Aging Project participants free of clinical stroke, dementia, and heart failure
(n=318, 73+/-7 years, 58% male, 39% mild cognitive impairment) underwent brain
magnetic resonance imaging, cardiac magnetic resonance, and neuropsychological
assessment. Voxelwise analyses related LV mass index (g/m2) to diffusion tensor
imaging metrics. Models adjusted for age, sex, education, race/ethnicity,
Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E
epsilon4 status. Secondary analyses included a LV mass index*diagnosis
interaction term with follow-up models stratified by diagnosis. With identical
covariates, linear regression models related LV mass index to neuropsychological
performances. Increased LV mass index related to altered white matter
microstructure (P<0.05). In models stratified by diagnosis, associations between
LV mass index and diffusion tensor imaging were present among mild cognitive
impairment participants only (P<0.05). LV mass index was related only to worse
visuospatial memory performance (beta=-0.003, P=0.036), an observation that would
not withstand correction for multiple testing. CONCLUSIONS: In the absence of
prevalent heart failure and clinical stroke, increased LV mass index corresponds
to altered white matter microstructure, particularly among older adults with
clinical symptoms of prodromal dementia. Findings highlight the potential link
between subclinical LV remodeling and cerebral white matter microstructure
vulnerability.
PMID- 29945918
TI - Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a
randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding
phase 2 study.
AB - OBJECTIVES: To evaluate the efficacy and safety of risankizumab, a humanised
monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), in
patients with active ankylosing spondylitis (AS). METHODS: A total of 159
patients with biological-naive AS, with active disease (Bath Ankylosing
Spondylitis Disease Activity Index score of >=4), were randomised (1:1:1:1) to
risankizumab (18 mg single dose, 90 mg or 180 mg at day 1 and weeks 8, 16 and 24)
or placebo over a 24-week blinded period. The primary outcome was a 40%
improvement in Assessment in Spondylo Arthritis International Society (ASAS40) at
week 12. Safety was assessed in patients who received at least one dose of study
drug. RESULTS: At week 12, ASAS40 response rates were 25.5%, 20.5% and 15.0% in
the 18 mg, 90 mg and 180 mg risankizumab groups, respectively, compared with
17.5% in the placebo group. The estimated difference in proportion between the
180 mg risankizumab and placebo groups (primary endpoint) was -2.5% (95% CI -21.8
to 17.0; p=0.42). Rates of adverse events were similar in all treatment groups.
CONCLUSIONS: Treatment with risankizumab did not meet the study primary endpoint
and showed no evidence of clinically meaningful improvements compared with
placebo in patients with active AS, suggesting that IL-23 may not be a relevant
driver of disease pathogenesis and symptoms in AS. TRIAL REGISTRATION NUMBER:
NCT02047110; Pre-results.
PMID- 29945919
TI - Protective effects of antimalarials in Chinese patients with systemic lupus
erythematosus.
PMID- 29945920
TI - Cereblon modulator iberdomide induces degradation of the transcription factors
Ikaros and Aiolos: immunomodulation in healthy volunteers and relevance to
systemic lupus erythematosus.
AB - OBJECTIVES: IKZF1 and IKZF3 (encoding transcription factors Ikaros and Aiolos)
are susceptibility loci for systemic lupus erythematosus (SLE). The pharmacology
of iberdomide (CC-220), a cereblon (CRBN) modulator targeting Ikaros and Aiolos,
was studied in SLE patient cells and in a phase 1 healthy volunteer study.
METHODS: CRBN, IKZF1 and IKZF3 gene expression was measured in peripheral blood
mononuclear cells (PBMC) from patients with SLE and healthy volunteers. Ikaros
and Aiolos protein levels were measured by Western blot and flow cytometry. Anti
dsDNA and anti-phospholipid autoantibodies were measured in SLE PBMC cultures
treated for 7 days with iberdomide. Fifty-six healthy volunteers were randomised
to a single dose of iberdomide (0.03-6 mg, n=6 across seven cohorts) or placebo
(n=2/cohort). CD19+ B cells, CD3+ T cells and intracellular Aiolos were measured
by flow cytometry. Interleukin (IL)-2 and IL-1beta production was stimulated with
anti-CD3 and lipopolysaccharide, respectively, in an ex vivo whole blood assay.
RESULTS: SLE patient PBMCs expressed significantly higher CRBN (1.5-fold), IKZF1
(2.1-fold) and IKZF3 (4.1-fold) mRNA levels compared with healthy volunteers.
Iberdomide significantly reduced Ikaros and Aiolos protein levels in B cells, T
cells and monocytes. In SLE PBMC cultures, iberdomide inhibited anti-dsDNA and
anti-phospholipid autoantibody production (IC50 ~10 nM). Single doses of
iberdomide (0.3-6 mg) in healthy volunteers decreased intracellular Aiolos
(minimum mean per cent of baseline: ~12%-28% (B cells); ~0%-33% (T cells)),
decreased absolute CD19+ B cells, increased IL-2 and decreased IL-1beta
production ex vivo. CONCLUSIONS: These findings demonstrate pharmacodynamic
activity of iberdomide and support its further clinical development for the
treatment of SLE. TRIAL REGISTRATION NUMBER: NCT01733875; Results.
PMID- 29945922
TI - Response to: 'Protective effects of antimalarials in Chinese patients with
systemic lupus erythematosus' by Wang et al.
PMID- 29945921
TI - Apoptosis-derived membrane vesicles drive the cGAS-STING pathway and enhance type
I IFN production in systemic lupus erythematosus.
AB - OBJECTIVE: Despite the importance of type I interferon (IFN-I) in systemic lupus
erythematosus (SLE) pathogenesis, the mechanisms of IFN-I production have not
been fully elucidated. Recognition of nucleic acids by DNA sensors induces IFN-I
and interferon-stimulated genes (ISGs), but the involvement of cyclic guanosine
monophosphate (GMP)-AMP synthase (cGAS) and stimulator of interferon genes
(STING) in SLE remains unclear. We studied the role of the cGAS-STING pathway in
the IFN-I-producing cascade driven by SLE serum. METHODS: We collected sera from
patients with SLE (n=64), patients with other autoimmune diseases (n=31) and
healthy controls (n=35), and assayed them using a cell-based reporter system that
enables highly sensitive detection of IFN-I and ISG-inducing activity. We used
Toll-like receptor-specific reporter cells and reporter cells harbouring
knockouts of cGAS, STING and IFNAR2 to evaluate signalling pathway-dependent ISG
induction. RESULTS: IFN-I bioactivity and ISG-inducing activities of serum were
higher in patients with SLE than in patients with other autoimmune diseases or
healthy controls. ISG-inducing activity of SLE sera was significantly reduced in
STING-knockout reporter cells, and STING-dependent ISG-inducing activity
correlated with disease activity. Double-stranded DNA levels were elevated in
SLE. Apoptosis-derived membrane vesicles (AdMVs) from SLE sera had high ISG
inducing activity, which was diminished in cGAS-knockout or STING-knockout
reporter cells. CONCLUSIONS: AdMVs in SLE serum induce IFN-I production through
activation of the cGAS-STING pathway. Thus, blockade of the cGAS-STING axis
represents a promising therapeutic target for SLE. Moreover, our cell-based
reporter system may be useful for stratifying patients with SLE with high ISG
inducing activity.
PMID- 29945923
TI - Restricted immune activation and internalisation of anti-idiotype complexes
between drug and antidrug antibodies.
AB - OBJECTIVES: Therapeutic antibodies can provoke an antidrug antibody (ADA)
response, which can form soluble immune complexes with the drug in potentially
high amounts. Nevertheless, ADA-associated adverse events are usually rare,
although with notable exceptions including infliximab. The immune activating
effects and the eventual fate of these 'anti-idiotype' complexes are poorly
studied, hampering assessment of ADA-associated risk of adverse events. We
investigated the in vitro formation and biological activities of ADA-drug anti
idiotype immune complexes using patient-derived monoclonal anti-infliximab
antibodies. METHODS: Size distribution and conformation of ADA-drug complexes
were characterised by size-exclusion chromatography and electron microscopy.
Internalisation of and immune activation by complexes of defined size was
visualised with flow imaging, whole blood cell assay and C4b/c ELISA. RESULTS:
Size and conformation of immune complexes depended on the concentrations and
ratio of drug and ADA; large complexes (>6 IgGs) formed only with high ADA
titres. Macrophages efficiently internalised tetrameric and bigger complexes in
vitro, but not dimers. Corroborating these results, ex vivo analysis of patient
sera demonstrated only dimeric complexes in circulation.No activation of immune
cells by anti-idiotype complexes was observed, and only very large complexes
activated complement. Unlike Fc-linked hexamers, anti-idiotype hexamers did not
activate complement, demonstrating that besides size, conformation governs immune
complex potential for triggering effector functions. CONCLUSIONS: Anti-idiotype
ADA-drug complexes generally have restricted immune activation capacity. Large,
irregularly shaped complexes only form at high concentrations of both drug and
ADA, as may be achieved during intravenous infusion of infliximab, explaining the
rarity of serious ADA-associated adverse events.
PMID- 29945924
TI - The 7-day contraceptive hormone-free interval should be consigned to history.
AB - AIM: This review summarises the available data on the disadvantages of the 7-day
contraceptive-free interval (CFI) of combined oral contraceptives (COCs), in
contrast to shorter CFIs or continuous use - including flexible regimens - and
provides recommendations for practice. METHODS: Relevant papers were identified
by Medline and PubMed. The final reference list was generated on the basis of
relevance to the review, with priority given to systematic reviews and randomised
controlled trials. RESULTS: There is considerable inter- and intra-individual
variation in the absorption and metabolism of COCs. Even with perfect use, the
loss of endocrine suppression during the standard 7-day CFI allows follicular
development with the risk of escape ovulation in a vulnerable minority. This risk
increases in typical users whenever the CFI is prolonged: late restarts are a
common reason for pill omissions. Shortening or eliminating the CFI improves
contraceptive efficacy using the lowest doses available, without evidence to date
of compromised safety. CONCLUSIONS: There is no scientific evidence to support a
7-day CFI and it should be replaced either by a continuous flexible regimen, or
extended regimens with a shortened CFI, prescribed first-line. In women
preferring a monthly 'bleed', a 4-day CFI similarly provides a greater safety
margin when pills are omitted.
PMID- 29945925
TI - Gastrointestinal sequelae after surgery for necrotising enterocolitis: a
systematic review and meta-analysis.
AB - OBJECTIVES: To document what types of gastrointestinal sequelae were described
after surgery for necrotising enterocolitis (NEC) and to analyse their frequency.
DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, EMBASE and
the Cochrane library (CENTRAL) from 1990 to October 2016. ELIGIBILITY CRITERIA
FOR SELECTING STUDIES: We included studies, which provided original data on the
occurrence of gastrointestinal sequelae in patients surviving surgery for NEC.
Meta-analysis and metaregression to assess heterogeneity were performed for
studies including 10 or more patients with gastrointestinal strictures,
recurrence of NEC, intestinal failure (IF) and adhesion ileus. RESULTS:
Altogether 58 studies, including 4260 patients, met the inclusion criteria.
Strictures were reported to occur in 24% (95% CI 17% to 31%) of surviving
patients, recurrence of NEC in 8% (95% CI 3% to 15%), IF in 13% (95% CI 7% to
19%) and adhesion ileus in 6% (95% CI 4% to 9%). Strictures were more common
following enterostomy (30%; 95% CI 23% to 37%) than after primary anastomosis
(8%; 95% CI 0% to 23%) and occurred more often after enterostomy without bowel
resection than with bowel resection. We found considerable heterogeneity in the
weighted average frequency of all sequelae (I2 range: 38%-90%). Intestinal
outcomes were poorly defined, there were important differences in study
populations and designs, and the reported findings bear a substantial risk of
bias. CONCLUSIONS: Gastrointestinal sequelae in neonates surviving surgery for
NEC are frequent. Long-term follow-up assessing defined gastrointestinal outcomes
is warranted.
PMID- 29945926
TI - Anticancer effect of histone deacetylase inhibitor scriptaid as a single agent
for hepatocellular carcinoma.
AB - Recurrence is one of the major causes of poor prognosis for patients with
hepatocellular carcinoma (HCC), and drug resistance is closely associated with
disease recurrence. Histone deacetylase (HDAC) inhibitor scriptaid functions as
an anticancer agent in many different types of tumors, but its possible roles in
HCC progression have not been explored to date. Herein, we show that HDAC
inhibitor scriptaid decreases HCC cell proliferation and induces cell cycle G2/M
phase arrest in a dose-dependent manner. Furthermore, scriptaid triggered HCC
cell death via transcriptional activation of p21 and subsequent elevated global
H3Ac levels. Importantly, we found that scriptaid showed robust antitumor
activity against HCC. Thus, our findings indicate that HDAC inhibitor scriptaid
could be an important potential candidate for treatment of HCC patients.
PMID- 29945927
TI - A paternal methyl donor depleted diet leads to increased anxiety- and depression
like behavior in adult rat offspring.
AB - Epigenetic mechanisms such as DNA methylation elicit lasting changes in gene
expression and likely mediate gene-environment interactions that shape brain
development, behavior, and emotional health. Myriad environmental factors
influence DNA methylation, including methyl donor content in the paternal diet,
could influence methylation in offspring via changes in the paternal germ line.
The present study examines the effects of paternal methyl donor dietary
deficiency on offspring's emotional behaviors, including anxiety, social
interaction, and depression-like behavior. We previously found that rats bred to
display high levels of anxiety- and depression-like behavior exhibit diminished
DNA methylation in the amygdala. We also observed that depleting dietary methyl
donor content exacerbated the rats' already high levels of anxiety- and
depression-like behavior. Here we sought to determine whether paternal dietary
methyl donor depletion elicits intergenerational effects on first generation (F1)
offspring's behavior (potentially triggering a similar increase in anxiety-
and/or depression-like behavior). Thus, adult male rats prone to high
anxiety/depression-like behavior, were fed either a methyl donor depleted (DEP)
or control (CON) diet for 5 weeks prior to mating. They were paired with females
and resultant F1 male offspring were subjected to a behavioral test battery in
adulthood. F1-DEP offspring showed a similar behavioral profile to the F0 males,
including greater depression-like behavior in the forced swim test (FST) and
increased anxiety-like behavior in the open field test (OFT). Future work will
interrogate molecular changes in the brains of F1 offspring that mediate these
intergenerational effects of paternal methyl donor dietary content on offspring
emotional behavior.
PMID- 29945928
TI - The US Experience of the Wearable Cardioverter-Defibrillator in Pediatric
Patients.
AB - BACKGROUND: Certain pediatric patients are at risk for sudden cardiac death. The
wearable cardioverter-defibrillator (WCD) can be used in clinical situations in
which implantable cardioverter-defibrillator placement is not ideal. The
objectives of the study are to examine the effectiveness, safety, and compliance
of the WCD in the identification and treatment of life-threatening ventricular
arrhythmias in pediatric patients. METHODS: All United States pediatric patients
<18 years who wore a WCD, from 2009 to 2016 were retrospectively reviewed.
RESULTS: In total, 455 patients were identified. The median age was 15 (3-17)
years, median duration of WCD use was 33 (1-999) days and median patient wear
time was 20.6 (0.3-23.8) hours per day. The population was divided into 2 groups:
(1) patients with implantable cardioverter-defibrillator problem, n=63 and (2)
patients with nonimplantable cardioverter-defibrillator problem, n=392. Wear time
per day was >20 hours in both groups. Wear duration was shorter in the
implantable cardioverter-defibrillator problem group, 26 days versus 35 days,
P<0.05. There were 7 deaths (1.5%); all not wearing WCD at time of death. Eight
patients (1.8%) received at least 1 WCD shock treatment. Of the 6 patients (1.3%)
who had appropriate therapy, there were 7 episodes of either polymorphic
ventricular tachycardia or ventricular fibrillation with a total of 13 treatments
delivered. All episodes were successfully converted and the patients survived.
CONCLUSIONS: The WCD has overall adequate compliance with appropriate wear times
and wear durations in pediatric patients. The WCD is safe and effective in
treating ventricular arrhythmias that can lead to sudden cardiac death in
pediatric patients.
PMID- 29945929
TI - Minimally Invasive Implantation of a Micropacemaker Into the Pericardial Space.
AB - BACKGROUND: Permanent cardiac pacemakers require invasive procedures with
complications often related to long pacemaker leads. We are developing a
percutaneous pacemaker for implantation of an entire pacing system into the
pericardial space. METHODS: Percutaneous micropacemaker implantations were
performed in 6 pigs (27.4-34.1 kg) using subxyphoid access to the pericardial
space. Modifications in the implantation methods and hardware were made after
each experiment as the insertion method was optimized. In the first 5 animals,
nonfunctional pacemaker devices were studied. In the final animal, a functional
pacemaker was implanted. RESULTS: Successful placement of the entire
nonfunctional pacing system into the pericardial space was demonstrated in 2 of
the first 5 animals, and successful implantation and capture was achieved using a
functional system in the last animal. A sheath was developed that allows
retractable features to secure positioning within the pericardial space. In
addition, a miniaturized camera with fiberoptic illumination allowed
visualization of the implantation site before electrode insertion into
myocardium. All animals studied during follow-up survived without symptoms after
the initial postoperative period. CONCLUSIONS: A novel micropacemaker system
allows cardiac pacing without entering the vascular space or surgical exposure of
the heart. This pericardial pacemaker system may be an option for a large number
of patients currently requiring transvenous pacemakers but is particularly
relevant for patients with restricted vascular access, young children, or those
with congenital heart disease who require epicardial access.
PMID- 29945930
TI - Contributions of Nrf2 to Puerarin Prevention of Cardiac Hypertrophy and its
Metabolic Enzymes Expression in Rats.
AB - Previous evidence has suggested that puerarin may attenuate cardiac hypertrophy;
however, the potential mechanisms have not been determined. Moreover, the use of
puerarin is limited by severe adverse events, including intravascular hemolysis.
This study used a rat model of abdominal aortic constriction (AAC)-induced
cardiac hypertrophy to evaluate the potential mechanisms underlying the
attenuating efficacy of puerarin on cardiac hypertrophy, as well as the metabolic
mechanisms of puerarin involved. We confirmed that puerarin (50 mg/kg per day)
significantly attenuated cardiac hypertrophy, upregulated Nrf2, and decreased
Keap1 in the myocardium. Moreover, puerarin significantly promoted Nrf2 nuclear
accumulation in parallel with the upregulated downstream proteins, including heme
oxygenase 1, glutathione transferase P1, and NAD(P)H:quinone oxidoreductase 1.
Similar results were obtained in neonatal rat cardiomyocytes (NRCMs) treated with
angiotensin II (Ang II; 1 MUM) and puerarin (100 MUM), whereas the silencing of
Nrf2 abolished the antihypertrophic effects of puerarin. The mRNA and protein
levels of UGT1A1 and UGT1A9, enzymes for puerarin metabolism, were significantly
increased in the liver and heart tissues of AAC rats and Ang II-treated NRCMs.
Interestingly, the silencing of Nrf2 attenuated the puerarin-induced upregulation
of UGT1A1 and UGT1A9. The results of chromatin immunoprecipitation-quantitative
polymerase chain reaction indicated that the binding of Nrf2 to the promoter
region of Ugt1a1 or Ugt1a9 was significantly enhanced in puerarin-treated
cardiomyocytes. These results suggest that Nrf2 is the key regulator of
antihypertrophic effects and upregulation of the metabolic enzymes UGT1A1 and
UGT1A9 of puerarin. The autoregulatory circuits between puerarin and Nrf2-induced
UGT1A1/1A9 are beneficial to attenuate adverse effects and maintain the
pharmacologic effects of puerarin.
PMID- 29945931
TI - Differential Tolerance to FTY720-Induced Antinociception in Acute Thermal and
Nerve Injury Mouse Pain Models: Role of Sphingosine-1-Phosphate Receptor
Adaptation.
AB - The immunomodulatory prodrug 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol
(FTY720), which acts as an agonist for sphingosine-1-phosphate (S1P) receptors
(S1PR) when phosphorylated, is proposed as a novel pain therapeutic. In this
study, we assessed FTY720-mediated antinociception in the radiant heat tail-flick
test and in the chronic constriction injury (CCI) model of neuropathic pain in
mice. FTY720 produced antinociception and antiallodynia, respectively, and these
effects were dose-dependent and mimicked by the S1PR1-selective agonist CYM-5442.
Repeated administration of FTY720 for 1 week produced tolerance to acute thermal
antinociception, but not to antiallodynia in the CCI model. S1PR-stimulated
[35S]GTPgammaS autoradiography revealed apparent desensitization of G protein
activation by S1P or the S1PR1 agonist 5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]
3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole (SEW-2871) throughout the brain.
Similar results were seen in spinal cord membranes, whereby the Emax value of
S1PR-stimulated [35S]GTPgammaS binding was greatly reduced in repeated FTY720
treated mice. These results suggest that S1PR1 is a primary target of FTY720 in
alleviating both acute thermal nociception and chronic neuropathic nociception.
Furthermore, the finding that tolerance develops to antinociception in the tail
flick test but not in chronic neuropathic pain suggests a differential mechanism
of FTY720 action between these models. The observation that repeated FTY720
administration led to desensitized S1PR1 signaling throughout the central nervous
system suggests the possibility that S1PR1 activation drives the acute thermal
antinociceptive effects, whereas S1PR1 desensitization mediates the following: 1)
tolerance to thermal antinociceptive actions of FTY720 and 2) the persistent
antiallodynic effects of FTY720 in neuropathic pain by producing functional
antagonism of pronociceptive S1PR1 signaling.
PMID- 29945932
TI - Dopamine Transporter Dynamics of N-Substituted Benztropine Analogs with Atypical
Behavioral Effects.
AB - Atypical dopamine transporter (DAT) inhibitors, despite high DAT affinity, do not
produce the psychomotor stimulant and abuse profile of standard DAT inhibitors
such as cocaine. Proposed contributing features for those differences include off
target actions, slow onsets of action, and ligand bias regarding DAT
conformation. Several 3alpha-(4',4''-difluoro-diphenylmethoxy)tropanes were
examined, including those with the following substitutions: N-(indole-3''-ethyl)-
(GA1-69), N-(R)-2''-amino-3''-methyl-n-butyl- (GA2-50), N-2''aminoethyl- (GA2
99), and N-(cyclopropylmethyl)- (JHW013). These compounds were previously
reported to have rapid onset of behavioral effects and were presently evaluated
pharmacologically alone or in combination with cocaine. DAT conformational mode
was assessed by substituted-cysteine accessibility and molecular dynamics (MD)
simulations. As determined by substituted-cysteine alkylation, all BZT analogs
except GA2-99 showed bias for a cytoplasmic-facing DAT conformation, whereas
cocaine stabilized the extracellular-facing conformation. MD simulations
suggested that several analog-DAT complexes formed stable R85-D476 "outer gate"
bonds that close the DAT to extracellular space. GA2-99 diverged from this
pattern, yet had effects similar to those of other atypical DAT inhibitors.
Apparent DAT association rates of the BZT analogs in vivo were slower than that
for cocaine. None of the compounds was self-administered or stimulated
locomotion, and each blocked those effects of cocaine. The present findings
provide more detail on ligand-induced DAT conformations and indicate that aspects
of DAT conformation other than "open" versus "closed" may facilitate predictions
of the actions of DAT inhibitors and may promote rational design of potential
treatments for psychomotor-stimulant abuse.
PMID- 29945934
TI - Newer Generation Ultra-Thin Strut Drug-Eluting Stents versus Older Second
Generation Thicker Strut Drug-Eluting Stents for Coronary Artery Disease: A Meta
Analysis of Randomized Trials.
AB - Background -Contemporary second-generation drug-eluting stents (DES) have
superior efficacy and safety compared with early generation stents in patients
undergoing percutaneous coronary intervention (PCI), in part related to their
thinner struts. Whether newer generation ultra-thin DES further improve clinical
outcomes compared with older second-generation thicker strut DES is unknown.
Methods -We searched PUBMED, EMBASE, and CENTRAL for randomized clinical trials
that compared newer generation ultra-thin strut DES (defined as strut thickness
<70 microns) versus thicker strut second-generation DES and reported clinical
outcomes. The primary outcome was target lesion failure (TLF) (composite of
cardiovascular death, target vessel myocardial infarction (MI) or ischemia-driven
target lesion revascularization (TLR)) evaluated at 1-year follow-up. Tests for
subgroup effects based on the ultra-thin strut DES type and based on the
comparator DES type were performed using meta-regression analysis. Results -We
identified 10 trials that randomized 11,658 patients and evaluated 3 newer
generation ultra-thin strut DES: Orsiro stent (60 MUm), MiStent (64 MUm) and
BioMime (65 MUm). When compared with thicker strut second-generation DES, newer
generation ultra-thin strut DES were associated with a 16% reduction in TLF
(RR=0.84; 95% CI 0.72-0.99) driven by less MI (RR=0.80; 95% CI 0.65-0.99). Ultra
thin strut DES were also associated with qualitatively lower rates of any stent
thrombosis (RR=0.72; 95% CI 0.51-1.01). Tests for subgroup effects based on the
ultra-thin strut DES type (P=0.58) and the comparator DES type (P=0.98) were not
significant, suggesting consistent outcomes across the three ultra-thin strut DES
and with the different DES comparators. Conclusions -In patients undergoing PCI,
newer generation ultra-thin strut DES further improve 1-year clinical outcomes
compared with contemporary thicker strut second-generation DES.
PMID- 29945933
TI - Modulation of caveolae by insulin/IGF-1 signaling regulates aging of
Caenorhabditis elegans.
AB - Reducing insulin/IGF-1 signaling (IIS) extends lifespan, promotes protein
homeostasis (proteostasis), and elevates stress resistance of worms, flies, and
mammals. How these functions are orchestrated across the organism is only
partially understood. Here, we report that in the nematode Caenorhabditis
elegans, the IIS positively regulates the expression of caveolin-1 (cav-1), a
gene which is primarily expressed in neurons of the adult worm and underlies the
formation of caveolae, a subtype of lipid microdomains that serve as platforms
for signaling complexes. Accordingly, IIS reduction lowers cav-1 expression and
lessens the quantity of neuronal caveolae. Reduced cav-1 expression extends
lifespan and mitigates toxic protein aggregation by modulating the expression of
aging-regulating and signaling-promoting genes. Our findings define caveolae as
aging-governing signaling centers and underscore the potential for cav-1 as a
novel therapeutic target for the promotion of healthy aging.
PMID- 29945935
TI - Quantifying and Localizing the Mitochondrial Proteome Across Five Tissues in A
Mouse Population.
AB - We have used SWATH mass spectrometry to quantify 3648 proteins across 76
proteomes collected from genetically diverse BXD mouse strains in two fractions
(mitochondria and total cell) from five tissues: liver, quadriceps, heart, brain,
and brown adipose (BAT). Across tissues, expression covariation between genes'
proteins and transcripts-measured in the same individuals-broadly aligned.
Covariation was however far stronger in certain subsets than others: only 8% of
transcripts in the lowest expression and variance quintile covaried with their
protein, in contrast to 65% of transcripts in the highest quintiles. Key
functional differences among the 3648 genes were also observed across tissues,
with electron transport chain (ETC) genes particularly investigated. ETC complex
proteins covary and form strong gene networks according to tissue, but their
equivalent transcripts do not. Certain physiological consequences, such as the
depletion of ATP synthase in BAT, are thus obscured in transcript data. Lastly,
we compared the quantitative proteomic measurements between the total cell and
mitochondrial fractions for the five tissues. The resulting enrichment score
highlighted several hundred proteins which were strongly enriched in
mitochondria, which included several dozen proteins were not reported in
literature to be mitochondrially localized. Four of these candidates were
selected for biochemical validation, where we found MTAP, SOAT2, and IMPDH2 to be
localized inside the mitochondria, whereas ABCC6 was in the mitochondria
associated membrane. These findings demonstrate the synergies of a multi-omics
approach to study complex metabolic processes, and this provides a resource for
further discovery and analysis of proteoforms, modified proteins, and protein
localization.
PMID- 29945936
TI - High Diabetes Distress Among Ethnic Minorities Is Not Explained by Metabolic,
Cardiovascular, or Lifestyle Factors: Findings From the Dutch Diabetes Pearl
Cohort.
AB - OBJECTIVE: Diabetes distress among patients from ethnic minorities is still
poorly understood. We investigated the association between ethnicity and diabetes
distress among ethnic minority groups of people with type 2 diabetes in the
Netherlands, focusing on the possible effects of glycemic control, lifestyle
factors, cardiovascular risk factors, and diabetes complications. RESEARCH DESIGN
AND METHODS: Cross-sectional data from the Dutch Diabetes Pearl cohort included
people with type 2 diabetes from primary, secondary, and tertiary diabetes care
programs. We used the 20-item Problem Areas in Diabetes Survey (PAID) scale to
assess diabetes distress; a score >=40 is considered to represent high distress.
Ethnicity was estimated on the basis of country of birth. Sociodemographic and
lifestyle data were self-reported; cardiovascular and metabolic data were
retrieved from medical charts. Logistic regression analysis determined the
association between ethnicity and diabetes distress, with Caucasians as the
reference group. RESULTS: Diabetes distress scores and ethnicity were available
for 4,191 people with type 2 diabetes: 3,684 were Caucasian, 83 were Asian, 51
were Moroccan, 92 were African, 134 were Latin American, 46 were Turkish, and 101
were Hindustani-Surinamese. Overall, participants in minority groups had worse
health outcomes than those of Caucasian descent, and diabetes distress was more
prevalent (ranging from 9.6 to 31.7%, compared with 5.8% among Caucasians), even
after adjusting for age, sex, education level, alcohol use, smoking, BMI, lipid
profile, HbA1c, medication use, and the presence of diabetes complications.
CONCLUSIONS: Among people with type 2 diabetes in the Netherlands, ethnicity is
independently associated with high diabetes distress. Further research is
warranted to explain the higher prevalence of diabetes distress in minority
groups and to develop effective interventions.
PMID- 29945937
TI - Risk stratification of smoldering multiple myeloma: predictive value of free
light chains and group-based trajectory modeling.
AB - We investigated the predictive role for serum free light chain ratio (FLCr)
>=100, bone marrow plasma cell (BMPC) >=60%, and evolving biomarkers through
group-based trajectory modeling (GBTM) as high-risk defining events in 273
smoldering multiple myeloma (SMM) patients with a median follow-up of 74 months.
FLCr >=100 was confirmed as a marker for high-risk progression with a median time
to progression (TTP) of 40 months with a 44% risk of progression of disease (PD)
at 2 years; however, 44% of FLCr >=100 also did not progress during follow-up.
For patients with BMPC >=60% by core biopsy, the median TTP was 31 months with a
2-year PD of 41%. GBTM established high-risk trajectories for evolving hemoglobin
(eHb; characterized as a 1.57 g/dL decrease in hemoglobin), evolving m-protein
(eMP; 64% increase in m-protein), and evolving differences in FLC (edFLC; 169%
increase in dFLC) within 1 year of diagnosis associated with a decreased median
TTP and an increased 2 year rate of PD. Of all the variables examined, we
identify a model where immunoparesis, eHb, eMP, and edFLC were significant
predictors for ultra-high-risk progression with a median TTP of only 13 months
with 3 or more variables present. Our results not only confirm a more modest 2
year PD associated with FLCr >=100 and BMPC >=60 but also suggest that eHb, eMP,
and edFLC may help identify an ultra-high-risk SMM group.
PMID- 29945938
TI - Distinct roles of mesenchymal stem and progenitor cells during the development of
acute myeloid leukemia in mice.
AB - Despite increasing evidence for the involvement of bone marrow (BM) hematopoietic
stem cell niche in leukemogenesis, how BM mesenchymal stem and progenitor cells
(MSPCs) contribute to leukemia niche formation and progression remains unclear.
Using an MLL-AF9 acute myeloid leukemia (AML) mouse model, we demonstrate dynamic
alterations of BM cellular niche components, including MSPCs and endothelial
cells during AML development and its association with AML engraftment. Primary
patient AML cells also induced similar niche alterations in xenografted mice. AML
cell infiltration in BM causes an expansion of early B-cell factor 2+ (Ebf2+)
MSPCs with reduced Cxcl12 expression and enhanced generation of more
differentiated mesenchymal progenitor cells. Importantly, in vivo fate-mapping
indicates that Ebf2+ MSPCs participated in AML niche formation. Ebf2+ cell
deletion accelerated the AML development. These data suggest that native BM MSPCs
may suppress AML. However, they can be remodeled by AML cells to form leukemic
niche that might contribute to AML progression. AML induced dysregulation of
hematopoietic niche factors like Angptl1, Cxcl12, Kitl, Il6, Nov, and Spp1 in AML
BM MSPCs, which was associated with AML engraftment and partially appeared before
the massive expansion of AML cells, indicating the possible involvement of the
niche factors in AML progression. Our study demonstrates distinct dynamic
features and roles of BM MSPCs during AML development.
PMID- 29945940
TI - The remarkable diversity of thrombotic thrombocytopenic purpura: a perspective.
AB - Understanding the autoimmune etiology of acquired thrombotic thrombocytopenic
purpura (TTP) has provided precision for the diagnosis and a rationale for
immunosuppressive treatment. These advances have also allowed recognition of the
remarkable clinical diversities of patients' initial presentations and their long
term outcomes. These diversities are illustrated by the stories of patients from
the Oklahoma TTP Registry. The initial presentation of TTP may be the discovery
of unexpected severe thrombocytopenia in a patient with minimal or no symptoms.
The patient may remain asymptomatic throughout treatment or may die suddenly
before treatment can be started. ADAMTS13 activity may be reported as normal in a
patient with characteristic clinical features of TTP, or the unexpected report of
ADAMTS13 deficiency in a patient with another established disorder may lead to
the discovery of TTP. ADAMTS13 activity during clinical remission is
unpredictable. ADAMTS13 activity may recover and remain normal, it may remain
severely deficient for many years, or it may become normal only many years after
recovery. Our treatment of initial episodes and management of patients after
recovery and during remission continue to change. The addition of rituximab to
the treatment of acute episodes and preemptive rituximab for patients with severe
ADAMTS13 deficiency during remission are reported to prevent relapse. Because TTP
is uncommon, there are few data to guide these changes. Therefore our patients'
stories are profoundly influential. Their stories are the foundation of our
experience, and our experience is the guide for our decisions.
PMID- 29945943
TI - Opioids and pain in the emergency department: a narrative crisis.
AB - The opioid crisis poses challenges to patients who come to the emergency
department (ED) in pain and the clinicians who have a duty to offer relief. In
search of help, patients often find suspicion. But clinicians have reasons to be
concerned about feeding addiction and its lethal consequences. This article
discusses the narrative challenges facing many clinicians in the ED tasked with
caring for complex patients in pain. It will discuss the many ways our brains are
influenced by story, and how this susceptibility is often beyond our grasp. And
yet, narrative and story skills present great opportunities for improving pain
management, not only when it comes to opioids, but by returning the focus back to
the patient in pain.
PMID- 29945941
TI - Integrative multi-omics analysis of intestinal organoid differentiation.
AB - Intestinal organoids accurately recapitulate epithelial homeostasis in vivo,
thereby representing a powerful in vitro system to investigate lineage
specification and cellular differentiation. Here, we applied a multi-omics
framework on stem cell-enriched and stem cell-depleted mouse intestinal organoids
to obtain a holistic view of the molecular mechanisms that drive differential
gene expression during adult intestinal stem cell differentiation. Our data
revealed a global rewiring of the transcriptome and proteome between intestinal
stem cells and enterocytes, with the majority of dynamic protein expression being
transcription-driven. Integrating absolute mRNA and protein copy numbers revealed
post-transcriptional regulation of gene expression. Probing the epigenetic
landscape identified a large number of cell-type-specific regulatory elements,
which revealed Hnf4g as a major driver of enterocyte differentiation. In summary,
by applying an integrative systems biology approach, we uncovered multiple layers
of gene expression regulation, which contribute to lineage specification and
plasticity of the mouse small intestinal epithelium.
PMID- 29945942
TI - Reclassification of the BRAF p.Ile208Val variant by case-level data sharing.
AB - The ClinVar database is a useful tool for patients and physicians to view variant
interpretations submitted by clinical and nonclinical labs. However, variants of
uncertain significance (VUS) in ClinVar can pose a significant burden on
patients. If possible, it is important to resolve discrepancies and uncertainties
surrounding interpreted variants. Here we highlight a case of a family who
received a report of a variant (c.622A>G, p.Ile208Val) in BRAF following prenatal
RASopathy testing. The variant had been previously classified by our laboratory
as a VUS, so the mother contacted our laboratory via ClinVar for further
information, which prompted reevaluation of the variant. Multiple sources of case
level data as well as the presence of the variant in the general population
yielded sufficient evidence to reclassify the variant as likely benign. This
reclassification alleviated significant concern for the family, and the child was
born healthy with no clinical manifestations of Noonan syndrome or a RASopathy.
PMID- 29945944
TI - Vesicular monoamine transporter type 2 inhibition can lead to effective and
tolerable management of tardive dyskinesia.
PMID- 29945939
TI - The use of defibrotide in blood and marrow transplantation.
AB - Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a
potentially life-threatening complication of conditioning during hematopoietic
stem cell transplantation (HSCT) or chemotherapy without HSCT, with a
historically reported mean incidence of 13.7% post-HSCT. Typical symptoms of
VOD/SOS may include hyperbilirubinemia, painful hepatomegaly, weight gain, and
ascites. Defibrotide, a polydisperse mixture of predominantly single-stranded
polydeoxyribonucleotides, is currently the only therapy approved to treat hepatic
VOD/SOS with pulmonary/renal dysfunction (ie, multiorgan dysfunction/multiorgan
failure [MOD/MOF]) following HSCT in the United States and to treat severe
hepatic VOD/SOS post-HSCT in the European Union. In preclinical and human
studies, defibrotide has demonstrated profibrinolytic, antithrombotic, anti
inflammatory, and angio-protective actions, thus promoting an anticoagulant
phenotype of the endothelium that protects and stabilizes the function of
endothelial cells. In a phase 3, historically controlled, multicenter trial in
adults and children with VOD/SOS and MOD/MOF (defibrotide: n = 102; controls
treated before defibrotide availability: n = 32), defibrotide resulted in
significantly greater day +100 survival following HSCT (38.2%) vs controls
(25.0%; propensity analysis-estimated between-group difference: 23%; P = .0109).
The most common adverse events (AEs) were hypotension and diarrhea; rates of
common hemorrhagic AEs were similar in the defibrotide and historical control
group (64% and 75%, respectively). In a phase 3 prophylaxis trial, defibrotide
was found to lower incidence of VOD/SOS in children (not an approved indication)
and reduce the incidence of graft-versus-host disease. This review describes the
development and clinical applications of defibrotide, focusing on its on-label
use in patients with VOD/SOS and MOD/MOF after HSCT.
PMID- 29945945
TI - Heartbeat: Is all physical activity beneficial for cardiovascular health?
PMID- 29945947
TI - Reply to 'Hormone use missing from UK Biobank cardiovascular disease study'.
PMID- 29945946
TI - Hormone use missing from UK Biobank cardiovascular disease study.
PMID- 29945948
TI - Response to: 'Contemporary management and outcomes in congenitally corrected
transposition of the great arteries' by Kutty et al.
PMID- 29945949
TI - Medical Management of the Systemic Right Ventricle.
PMID- 29945950
TI - Statistics in cardiovascular medicine: there is still gold in the old.
PMID- 29945951
TI - The whole is greater than the sum of its parts: combining classical statistical
and machine intelligence methods in medicine.
PMID- 29945952
TI - New uses for old drugs.
PMID- 29945953
TI - Self-repopulating recipient bone marrow resident macrophages promote long-term
hematopoietic stem cell engraftment.
AB - Distinct subsets of resident tissue macrophages are important in hematopoietic
stem cell niche homeostasis and erythropoiesis. We used a myeloid reporter gene
(Csf1r-eGFP) to dissect the persistence of bone marrow and splenic macrophage
subsets following lethal irradiation and autologous hematopoietic stem cell
transplantation in a mouse model. Multiple recipient bone marrow and splenic
macrophage subsets survived after autologous hematopoietic stem cell
transplantation with organ-specific persistence kinetics. Short-term persistence
(5 weeks) of recipient resident macrophages in spleen paralleled the duration of
extramedullary hematopoiesis. In bone marrow, radiation-resistant recipient
CD169+ resident macrophages and erythroid-island macrophages self-repopulated
long-term after transplantation via autonomous cell division. Posttransplant peak
expansion of recipient CD169+ resident macrophage number in bone marrow aligned
with the persistent engraftment of phenotypic long-term reconstituting
hematopoietic stem cells within bone marrow. Selective depletion of recipient
CD169+ macrophages significantly compromised the engraftment of phenotypic long
term reconstituting hematopoietic stem cells and consequently impaired
hematopoietic reconstitution. Recipient bone marrow resident macrophages are
essential for optimal hematopoietic stem cell transplantation outcomes and could
be an important consideration in the development of pretransplant conditioning
therapies and/or chemoresistance approaches.
PMID- 29945954
TI - Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a
randomized controlled trial.
AB - Management of children with newly diagnosed immune thrombocytopenia (ITP)
consists of careful observation or immunomodulatory treatment. Observational
studies suggest a lower risk for chronic ITP in children after intravenous
immunoglobulin (IVIg) treatment. In this multicenter randomized trial, children
aged 3 months to 16 years with newly diagnosed ITP, platelet counts 20 * 109/L or
less, and mild to moderate bleeding were randomly assigned to receive either a
single infusion of 0.8 g/kg IVIg or careful observation. Primary outcome was
development of chronic ITP, which at the time of study initiation was defined as
a platelet count lower than 150 * 109/L after 6 months. Two hundred six children
were allocated to receive IVIg (n = 102) or careful observation (n = 104).
Chronic ITP occurred in 18.6% of the patients in the IVIg group and 28.9% in the
observation group (relative risk [RR], 0.64; 95% confidence interval [CI], 0.38
1.08). Platelet counts lower than 100 * 109/L at 12 months (current definition of
chronic ITP) were observed in 10% of children in the IVIg group and 12% in the
observation group (RR, 0.83; 95% CI, 0.38-1.84). Complete response rates in the
first 3 months were significantly higher in the IVIg group. Immunoglobulin G Fc
receptor IIb genetic variations were associated with early complete response in
both groups. Grade 4 to 5 bleeding occurred in 9% of the patients in the
observation group vs 1% in the IVIg group. This trial was registered at
www.trialregister.nl as NTR 1563.
PMID- 29945956
TI - Inspiratory muscle training in COPD: can data finally beat emotion?
PMID- 29945957
TI - Preventive healthcare strategies are a matter of social justice.
PMID- 29945955
TI - Preterm Neuroimaging and School-Age Cognitive Outcomes.
AB - BACKGROUND AND OBJECTIVES: Children born extremely preterm are at risk for
cognitive difficulties and disability. The relative prognostic value of neonatal
brain MRI and cranial ultrasound (CUS) for school-age outcomes remains unclear.
Our objectives were to relate near-term conventional brain MRI and early and late
CUS to cognitive impairment and disability at 6 to 7 years among children born
extremely preterm and assess prognostic value. METHODS: A prospective study of
adverse early and late CUS and near-term conventional MRI findings to predict
outcomes at 6 to 7 years including a full-scale IQ (FSIQ) <70 and disability
(FSIQ <70, moderate-to-severe cerebral palsy, or severe vision or hearing
impairment) in a subgroup of Surfactant Positive Airway Pressure and Pulse
Oximetry Randomized Trial enrollees. Stepwise logistic regression evaluated
associations of neuroimaging with outcomes, adjusting for perinatal-neonatal
factors. RESULTS: A total of 386 children had follow-up. In unadjusted analyses,
severity of white matter abnormality and cerebellar lesions on MRI and adverse
CUS findings were associated with outcomes. In full regression models, both
adverse late CUS findings (odds ratio [OR] 27.9; 95% confidence interval [CI] 6.0
129) and significant cerebellar lesions on MRI (OR 2.71; 95% CI 1.1-6.7) remained
associated with disability, but only adverse late CUS findings (OR 20.1; 95% CI
3.6-111) were associated with FSIQ <70. Predictive accuracy of stepwise models
was not substantially improved with the addition of neuroimaging. CONCLUSIONS:
Severe but rare adverse late CUS findings were most strongly associated with
cognitive impairment and disability at school age, and significant cerebellar
lesions on MRI were associated with disability. Near-term conventional MRI did
not substantively enhance prediction of severe early school-age outcomes.
PMID- 29945958
TI - Combined MR Imaging of Oxygen Consumption and Supply Reveals Tumor Hypoxia and
Aggressiveness in Prostate Cancer Patients.
AB - The established role of hypoxia-induced signaling in prostate cancer growth,
metastasis, and response to treatment suggests that a method to image hypoxia in
tumors could aid treatment decisions. Here, we present consumption and supply
based hypoxia (CSH) imaging, an approach that integrates images related to oxygen
consumption and supply into a single image. This integration algorithm was
developed in patients with prostate cancer receiving hypoxia marker pimonidazole
prior to prostatectomy. We exploited the intravoxel incoherent motion (IVIM)
signal in diagnostic diffusion-weighted (DW) magnetic resonance (MR) images to
generate separate images of the apparent diffusion coefficient (ADC) and
fractional blood volume (fBV). ADC and fBV correlated with cell density (CD) and
blood vessel density (BVD) in histology and whole-mount sections from 35
patients, thus linking ADC to oxygen consumption and fBV to oxygen supply. Pixel
wise plots of ADC versus fBV were utilized to predict the hypoxia status of each
pixel in a tumor and to visualize the predicted value in a single image. The
hypoxic fraction (HFDWI) of CSH images correlated strongly (R2 = 0.66; n = 41)
with pimonidazole immunoscore (HSPimo); this relationship was validated in a
second pimonidazole cohort (R2 = 0.54; n = 54). We observed good agreement
between CSH images and pimonidazole staining in whole-mount sections. HFDWI
correlated with tumor stage and lymph node status, consistent with findings for
HSPimo Moreover, CSH imaging could be applied on histologic CD and BVD images,
demonstrating transferability to a histopathology assay. Thus, CSH represents a
robust approach for hypoxia imaging in prostate cancer that could easily be
translated into clinical practice.Significance: These findings present a novel
imaging strategy that indirectly measures tumor hypoxia and has potential
application in a wide variety of solid tumors and other imaging
modalities.Graphical Abstract:
http://cancerres.aacrjournals.org/content/canres/78/16/4774/F1.large.jpg Cancer
Res; 78(16); 4774-85. (c)2018 AACR.
PMID- 29945959
TI - FBXO22 Possesses Both Protumorigenic and Antimetastatic Roles in Breast Cancer
Progression.
AB - The molecular underpinnings behind malignant progression of breast cancer from a
localized lesion to an invasive and ultimately metastatic disease are
incompletely understood. Here, we report that F-box only protein 22 (FBXO22)
plays a dual role in mammary tumorigenesis and metastasis. FBXO22 was upregulated
in primary breast tumors and promoted cell proliferation and colony formation in
vitro and xenograft tumorigenicity in vivo Surprisingly, FBXO22 suppressed
epithelial-mesenchymal transition (EMT), cell motility, and invasiveness in vitro
and metastatic lung colonization in vivo Clinical data showed that expression
levels of FBXO22 were associated with favorable clinical outcomes, supporting the
notion that metastasis, rather than primary cancer, is the major determinant of
the mortality of patients with breast cancer. Mechanistic investigations further
revealed that FBXO22 elicits its antimetastatic effects by targeting SNAIL, a
master regulator of EMT and breast cancer metastasis, for ubiquitin-mediated
proteasomal degradation in a glycogen synthase kinase 3beta phosphorylation
dependent manner. Importantly, expression of SNAIL rescued FBXO22-mediated
suppression of EMT, cell migration, and invasion. A patient-derived tryptophan-to
arginine mutation at residue 52 (W52R) within the F-box domain impaired FBXO22
binding to the SKP1-Cullin1 complex and blocked FBXO22-mediated SNAIL
degradation, thus abrogating the ability of FBXO22 to suppress cell migration,
invasion, and metastasis. Collectively, these findings uncover an unexpected dual
role for FBXO22 in mammary tumorigenesis and metastatic progression and delineate
the mechanism of an oncogenic mutation of FBXO22 in breast cancer
progression.Significance: These findings highlight the paradoxical roles of
FBXO22 in breast cancer, as it promotes breast tumor cell proliferation but
prevents EMT and metastasis. Cancer Res; 78(18); 5274-86. (c)2018 AACR.
PMID- 29945960
TI - Upregulation of E3 Ubiquitin Ligase CBLC Enhances EGFR Dysregulation and
Signaling in Lung Adenocarcinoma.
AB - CBLC (CBL proto-oncogene c) belongs to the CBL protein family, which has E3
ubiquitin ligase activity toward activated receptor tyrosine kinases. CBLC is
frequently upregulated in non-small cell lung cancer (NSCLC), yet very little is
known about the functions of CBLC in tumorigenesis. Here we show that CBLC is an
epigenetically demethylated target and its expression can be upregulated in NSCLC
after treatment with the DNA methylation inhibitor 5'-azacytidine. Depletion of
CBLC significantly inhibited cell viability and clonogenicity in vitro and
reduced tumor growth in a xenograft model. CBLC silencing further sensitized EGFR
mutated NSCLC cells to treatment with tyrosine kinase inhibitors. Conversely,
ectopic expression of CBLC enhanced the activation of EGFR and downstream ERK1/2
signaling after ligand stimulation by competing with CBL for EGFR binding.
Analysis of ubiquitin linkages on activated EGFR (aEGFR) revealed that CBLC
ubiquitinated and positively regulated aEGFR stability through the conjugation of
polyubiquitin by K6 and K11 linkages. This CBLC-mediated polyubiquitination
promoted either preferential recycling of aEGFR back to the plasma membrane or
trafficking to the cell nucleus. IHC analyses revealed a positive correlation
between phospho-EGFR and CBLC in lung adenocarcinoma. In summary, we demonstrate
a novel mechanism by which aEGFR escapes lysosomal degradation in a
CBLC/ubiquitin-dependent manner to sustain its activation. Our work identifies
CBLC as a potential diagnostic biomarker and also points to its utilization as a
novel therapeutic target for NSCLC therapy.Significance: This work demonstrates
the role of CBLC expression as a diagnostic biomarker and potential therapeutic
target in lung adenocarcinoma. Cancer Res; 78(17); 4984-96. (c)2018 AACR.
PMID- 29945961
TI - Inhaled TLR9 Agonist Renders Lung Tumors Permissive to PD-1 Blockade by Promoting
Optimal CD4+ and CD8+ T-cell Interplay.
AB - Currently approved inhibitors of the PD-1/PD-L1 pathway represent a major advance
for the treatment of lung cancers, yet they are ineffective in a majority of
patients due to lack of preexisting T-cell reactivity. Here, we show that a TLR9
agonist delivered by inhalation is able to prime T-cell responses against poorly
immunogenic lung tumors and to complement the effects of PD-1 blockade. Inhaled
TLR9 agonist causes profound remodeling in tumor-bearing lungs, leading to the
formation of tertiary lymphoid structures adjacent to the tumors, CD8+ T-cell
infiltration into the tumors, dendritic cell expansion, and antibody production.
Inhalation of TLR9 agonist also increased the pool of functional PD-1lowT-bethigh
effector CD8+ T cells in tumor-bearing lungs. Effector CD8+ T cells generated by
inhaled TLR9 agonist treatment were licensed by PD-1 blockade to become highly
functional CTLs, leading to a durable rejection of both lung tumors and tumor
lesions outside the lungs. CD4+ T cells activated in response to inhaled TLR9
play a critical role in this process by controlling the proliferation, preventing
exhaustion, and guiding the differentiation of optimally functional CTLs. This
study characterizes a strategy to apply localized TLR9 stimulation to a tumor
type not accessible for direct injection, a strategy that may expand the
therapeutic potential of PD-1 blockade in non-small cell lung
cancer.Significance: These findings demonstrate that local delivery of a toll
like receptor 9 agonist can change the immune content of an entire organ and
enhance the efficacy of immune checkpoint inhibition.Graphical Abstract:
http://cancerres.aacrjournals.org/content/canres/78/17/4943/F1.large.jpg Cancer
Res; 78(17); 4943-56. (c)2018 AACR.
PMID- 29945962
TI - Loss of Estrogen-Regulated MIR135A1 at 3p21.1 Promotes Tamoxifen Resistance in
Breast Cancer.
AB - The dysregulation of miRNAs has been increasingly recognized as a critical
mediator of cancer development and progression. Here, we show that frequent
deletion of the MIR135A1 locus is associated with poor prognosis in primary
breast cancer. Forced expression of miR-135a decreased breast cancer progression,
while inhibition of miR-135a with a specific miRNA sponge elicited opposing
effects, suggestive of a tumor suppressive role of miR-135a in breast cancer.
Estrogen receptor alpha (ERalpha) bound the promoter of MIR135A1 for its
transcriptional activation, whereas tamoxifen treatment inhibited expression of
miR-135a in ERalpha+ breast cancer cells. miR-135a directly targeted ESR1, ESRRA,
and NCOA1, forming a negative feedback loop to inhibit ERalpha signaling. This
regulatory feedback between miR-135a and ERalpha demonstrated that miR-135a
regulated the response to tamoxifen. The tamoxifen-mediated decrease in miR-135a
expression increased the expression of miR-135a targets to reduce tamoxifen
sensitivity. Consistently, miR-135a expression was downregulated in ERalpha+
breast cancer cells with acquired tamoxifen resistance, while forced expression
of miR-135a partially resensitized these cells to tamoxifen. Tamoxifen resistance
mediated by the loss of miR-135a was shown to be partially dependent on the
activation of the ERK1/2 and AKT pathways by miR-135a-targeted genes. Taken
together, these results indicate that deletion of the MIR135A1 locus and
decreased miR-135a expression promote ERalpha+ breast cancer progression and
tamoxifen resistance.Significance: Loss of miR-135a in breast cancer disrupts an
estrogen receptor-induced negative feedback loop, perpetuating disease
progression and resistance to therapy.Graphical Abstract:
http://cancerres.aacrjournals.org/content/canres/78/17/4915/F1.large.jpg Cancer
Res; 78(17); 4915-28. (c)2018 AACR.
PMID- 29945963
TI - Cotargeting Ephrin Receptor Tyrosine Kinases A2 and A3 in Cancer Stem Cells
Reduces Growth of Recurrent Glioblastoma.
AB - Glioblastoma (GBM) carries a dismal prognosis and inevitably relapses despite
aggressive therapy. Many members of the Eph receptor tyrosine kinase (EphR)
family are expressed by GBM stem cells (GSC), which have been implicated in
resistance to GBM therapy. In this study, we identify several EphRs that mark a
therapeutically targetable GSC population in treatment-refractory, recurrent GBM
(rGBM). Using a highly specific EphR antibody panel and CyTOF (cytometry by time
of-flight), we characterized the expression of all 14 EphR in primary and
recurrent patient-derived GSCs to identify putative rGBM-specific EphR. EPHA2 and
EPHA3 coexpression marked a highly tumorigenic cell population in rGBM that was
enriched in GSC marker expression. Knockdown of EPHA2 and EPHA3 together led to
increased expression of differentiation marker GFAP and blocked clonogenic and
tumorigenic potential, promoting significantly higher survival in vivo Treatment
of rGBM with a bispecific antibody against EPHA2/A3 reduced clonogenicity in
vitro and tumorigenic potential of xenografted recurrent GBM in vivo via
downregulation of AKT and ERK and increased cellular differentiation. In
conclusion, we show that EPHA2 and EPHA3 together mark a GSC population in rGBM
and that strategic cotargeting of EPHA2 and EPHA3 presents a novel and rational
therapeutic approach for rGBM.Significance: Treatment of rGBM with a novel
bispecific antibody against EPHA2 and EPHA3 reduces tumor burden, paving the way
for the development of therapeutic approaches against biologically relevant
targets in rGBM. Cancer Res; 78(17); 5023-37. (c)2018 AACR.
PMID- 29945965
TI - Dietary Intakes and Circulating Concentrations of Branched-Chain Amino Acids in
Relation to Incident Type 2 Diabetes Risk Among High-Risk Women with a History of
Gestational Diabetes Mellitus.
AB - BACKGROUND: Circulating branched-chain amino acids (BCAAs; isoleucine, leucine,
valine) are consistently associated with increased type 2 diabetes (T2D) risk,
but the relationship with dietary intake of BCAAs is less clear. METHODS: The
longitudinal Nurses' Health Study II cohort conducted a blood collection from
1996 to 1999. We profiled plasma metabolites among 172 incident T2D cases and 175
age-matched controls from women reporting a history of gestational diabetes
before blood draw. We estimated dietary energy-adjusted BCAAs from food frequency
questionnaires. We used conditional logistic regression models to estimate odds
ratios (OR) and 95% CI of T2D risk across quartiles (Q1-Q4) of BCAAs, adjusting
for age, body mass index (BMI), physical activity, family history, and other
established risk factors. We also assessed joint exposure to below/above medians
of diet and plasma concentrations, with lower diet/lower plasma as reference.
RESULTS: Dietary and plasma BCAA concentrations were positively associated with
incident T2D (diet Q4 vs Q1 OR = 4.6, CI = 1.6, 13.4; plasma Q4 vs Q1 OR = 4.4,
CI = 1.4, 13.4). Modeling the joint association indicated that higher diet BCAAs
were associated with T2D when plasma concentrations were also higher (OR = 6.0,
CI = 2.1, 17.2) but not when concentrations were lower (OR = 1.6, CI = 0.61,
4.1). Conversely, higher plasma BCAAs were associated with increased T2D for
either lower or higher diet. CONCLUSIONS: Independent of BMI and other risk
factors, higher diet and plasma BCAA concentrations were associated with an
increased incident T2D risk among high-risk women with a history of gestational
diabetes, supporting impaired BCAA metabolism as conferring T2D risk.
PMID- 29945964
TI - Enhanced Glycolysis Supports Cell Survival in EGFR-Mutant Lung Adenocarcinoma by
Inhibiting Autophagy-Mediated EGFR Degradation.
AB - Oncogenic EGFR is essential for the development and growth of non-small cell lung
cancer (NSCLC), but the precise roles of EGFR in lung cancer metabolism remain
unclear. Here, we show that EGFR mutation-mediated enhancement of glycolysis is
critical for EGFR stability. EGFR knockdown significantly decreased levels of
glycolytic pathway intermediates via transcriptional regulation of glycolytic
genes. EGFR mutation-enhanced glycolysis was required for fueling the
tricarboxylic acid cycle, a critical component of EGFR stability. Nonsustained
ATP production enhanced reactive oxygen species accumulation and subsequent JNK
mediated activation of autophagy, which in turn induced EGFR degradation. Our
data show that EGFR-mutant NSCLCs require EGFR mutation-enhanced glycolysis to
maintain EGFR stability. This pathway may serve as an attractive therapeutic
target for EGFR-mutant NSCLCs.Significance: Enhanced glycolysis by EGFR mutation
is required for maintaining EGFR levels via inhibition of JNK-induced autophagy.
This provides a promising rationale for use of JNK activators in patients with
EGFR-mutated NSCLC. Cancer Res; 78(16); 4482-96. (c)2018 AACR.
PMID- 29945966
TI - Specifying a Gold Standard for the Validation of Fetal Fraction Estimation in
Prenatal Screening.
AB - BACKGROUND: An estimate of fetal fraction (FF) is needed for DNA-based screening
for trisomy 21 and other aneuploidies, but there is no gold standard to validate
FF measurement methods. We specify a gold standard and use it to validate a
method of measuring FF (SeqFF) in singleton pregnancies. METHODS: The gold
standard was a formula derived from 2 elements: (a) an estimate of the percentage
of DNA fragments in maternal plasma from chromosome 21 (%Ch21) in pregnancies
without trisomy 21, 18, or 13 (PU) and (b) calculation of %Ch21 with increasing
FF in trisomy 21 pregnancies (P21). The SeqFF method was evaluated by plotting
regression lines of %Ch21 and SeqFF estimates of FF in 31 singleton male and 31
female trisomy 21 pregnancies and comparing the regressions with the reference
line derived from the gold standard formula. RESULTS: The gold standard formula
was P21 = (1/2)PUFF + PU, with FF expressed as a proportion, or converting %Ch21
to multiples of the median (MoM), P21(MoM) = (1/2)FF + 1. Based on 3865
pregnancies, the PU was 1.2935%. The regression lines for trisomy 21 pregnancies
with male and female fetuses were almost identical to the gold standard reference
line (regression slopes in MoMs 0.52 and 0.50, respectively, compared with 0.50
for the gold standard reference line). CONCLUSIONS: The proposed gold standard
can be used to validate different methods of estimating FF in singleton
pregnancies. SeqFF is an accurate method of estimating FF.
PMID- 29945967
TI - Genomic Selection in Preliminary Yield Trials in a Winter Wheat Breeding Program.
AB - Genomic prediction (GP) is now routinely performed in crop plants to predict
unobserved phenotypes. The use of predicted phenotypes to make selections is an
active area of research. Here, we evaluate GP for predicting grain yield and
compare genomic and phenotypic selection by tracking lines advanced. We examined
four independent nurseries of F3:6 and F3:7 lines trialed at 6 to 10 locations
each year. Yield was analyzed using mixed models that accounted for experimental
design and spatial variations. Genotype-by-sequencing provided nearly 27,000 high
quality SNPs. Average genomic predictive ability, estimated for each year by
randomly masking lines as missing in steps of 10% from 10 to 90%, and using the
remaining lines from the same year as well as lines from other years in a
training set, ranged from 0.23 to 0.55. The predictive ability estimated for a
new year using the other years ranged from 0.17 to 0.28. Further, we tracked
lines advanced based on phenotype from each of the four F3:6 nurseries. Lines
with both above average genomic estimated breeding value (GEBV) and phenotypic
value (BLUP) were retained for more years compared to lines with either above
average GEBV or BLUP alone. The number of lines selected for advancement was
substantially greater when predictions were made with 50% of the lines from the
testing year added to the training set. Hence, evaluation of only 50% of the
lines yearly seems possible. This study provides insights to assess and integrate
genomic selection in breeding programs of autogamous crops.
PMID- 29945968
TI - On the Relationship Between High-Order Linkage Disequilibrium and Epistasis.
AB - A plausible explanation for statistical epistasis revealed in genome wide
association analyses is the presence of high order linkage disequilibrium (LD)
between the genotyped markers tested for interactions and unobserved functional
polymorphisms. Based on findings in experimental data, it has been suggested that
high order LD might be a common explanation for statistical epistasis inferred
between local polymorphisms in the same genomic region. Here, we empirically
evaluate how prevalent high order LD is between local, as well as distal,
polymorphisms in the genome. This could provide insights into whether we should
account for this when interpreting results from genome wide scans for statistical
epistasis. An extensive and strong genome wide high order LD was revealed between
pairs of markers on the high density 250k SNP-chip and individual markers
revealed by whole genome sequencing in the Arabidopsis thaliana 1001-genomes
collection. The high order LD was found to be more prevalent in smaller
populations, but present also in samples including several hundred individuals.
An empirical example illustrates that high order LD might be an even greater
challenge in cases when the genetic architecture is more complex than the common
assumption of bi-allelic loci. The example shows how significant statistical
epistasis is detected for a pair of markers in high order LD with a complex multi
allelic locus. Overall, our study illustrates the importance of considering also
other explanations than functional genetic interactions when genome wide
statistical epistasis is detected, in particular when the results are obtained in
small populations of inbred individuals.
PMID- 29945969
TI - A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated
with Neuroaxonal Dystrophy in Rottweiler Dogs.
AB - Canine neuroaxonal dystrophy (NAD) is a recessive, degenerative neurological
disease of young adult Rottweiler dogs (Canis lupus familiaris) characterized
pathologically by axonal spheroids primarily targeting sensory axon terminals. A
genome-wide association study of seven Rottweilers affected with NAD and 42
controls revealed a significantly associated region on canine chromosome 5 (CFA
5). Homozygosity within the associated region narrowed the critical interval to a
4.46 Mb haplotype (CFA5:11.28 Mb - 15.75 Mb; CanFam3.1) that associated with the
phenotype. Whole-genome sequencing of two histopathologically confirmed canine
NAD cases and 98 dogs unaffected with NAD revealed a homozygous missense mutation
within the Vacuolar Protein Sorting 11 (VPS11) gene (g.14777774T > C; p.H835R)
that was associated with the phenotype. These findings present the opportunity
for an antemortem test for confirming NAD in Rottweilers where the allele
frequency was estimated at 2.3%. VPS11 mutations have been associated with a
degenerative leukoencephalopathy in humans, and VSP11 should additionally be
included as a candidate gene for unexplained cases of human NAD.
PMID- 29945970
TI - The FCS-like zinc finger scaffold of the kinase SnRK1 is formed by the
coordinated actions of the FLZ domain and intrinsically disordered regions.
AB - The SNF1-related protein kinase 1 (SnRK1) is a heterotrimeric eukaryotic kinase
that interacts with diverse proteins and regulates their activity in response to
starvation and stress signals. Recently, the FCS-like zinc finger (FLZ) proteins
were identified as a potential scaffold for SnRK1 in plants. However, the
evolutionary and mechanistic aspect of this complex formation is currently
unknown. Here, in silico analyses predicted that FLZ proteins possess conserved
intrinsically disordered regions (IDRs) with a propensity for protein binding in
the N and C termini across the plant lineage. We observed that the Arabidopsis
FLZ proteins promiscuously interact with SnRK1 subunits, which formed different
isoenzyme complexes. The FLZ domain was essential for mediating the interaction
with SnRK1alpha subunits, whereas the IDRs in the N termini facilitated
interactions with the beta and betagamma subunits of SnRK1. Furthermore, the IDRs
in the N termini were important for mediating dimerization of different FLZ
proteins. Of note, the interaction of FLZ with SnRK1 was confined to cytoplasmic
foci, which colocalized with the endoplasmic reticulum. An evolutionary analysis
revealed that in general, the IDR-rich regions are under more relaxed selection
than the FLZ domain. In summary, the findings in our study reveal the structural
details, origin, and evolution of a land plant-specific scaffold of SnRK1 formed
by the coordinated actions of IDRs and structured regions in the FLZ proteins. We
propose that the FLZ protein complex might be involved in providing flexibility,
thus enhancing the binding repertoire of the SnRK1 hub in land plants.
PMID- 29945971
TI - Routes of phosphoryl group transfer during signal transmission and signal decay
in the dimeric sensor histidine kinase ArcB.
AB - The Arc (anoxic redox control) two-component system of Escherichia coli,
comprising ArcA as the response regulator and ArcB as the sensor histidine
kinase, modulates the expression of numerous genes in response to respiratory
growth conditions. Under reducing growth conditions, ArcB autophosphorylates at
the expense of ATP, and transphosphorylates ArcA via a His292 -> Asp576 -> His717
-> Asp54 phosphorelay, whereas under oxidizing growth conditions, ArcB catalyzes
the dephosphorylation of ArcA-P by a reverse Asp54 -> His717 -> Asp576 -> Pi
phosphorelay. However, the exact phosphoryl group transfer routes and the
molecular mechanisms determining their directions are unclear. Here, we show
that, during signal propagation, the His292 -> Asp576 and Asp576 -> His717
phosphoryl group transfers within ArcB dimers occur intra- and intermolecularly,
respectively. Moreover, we report that, during signal decay, the phosphoryl group
transfer from His717 to Asp576 takes place intramolecularly. In conclusion, we
present a mechanism that dictates the direction of the phosphoryl group transfer
within ArcB dimers and that enables the discrimination of the kinase and
phosphatase activities of ArcB.
PMID- 29945972
TI - Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription
factors in response to oxidative stress.
AB - Adaptations and responses to stress conditions are fundamental processes that all
cells must accomplish to maintain or restore cellular homeostasis. Cells have a
plethora of response pathways to mitigate the effect of different environmental
stressors. The transcriptional regulators transcription factor EB (TFEB) and
transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the
control of these stress pathways. Therefore, understanding their regulation under
different stress conditions is of great interest. Here, using a range of human
and murine cells, we show that TFEB and TFE3 are activated upon induction of
acute oxidative stress by sodium arsenite via an mTOR complex 1 (mTORC1)
independent process. We found that the mechanism of arsenite-stimulated TFEB and
TFE3 activation instead involves protein phosphatase 2A (PP2A)-mediated
dephosphorylation at Ser-211 and Ser-321, respectively. Depletion of either the
catalytic (PPP2CA+B) or regulatory (PPP2R2A/B55alpha) subunits of PP2A, as well
as PP2A inactivation with the specific inhibitor okadaic acid, abolished TFEB and
TFE3 activation in response to sodium arsenite. Conversely, PP2A activation by
ceramide or the sphingosine-like compound FTY720 was sufficient to induce TFE3
nuclear translocation. MS analysis revealed that PP2A dephosphorylates TFEB at
several residues, including Ser-109, Ser-114, Ser-122, and Ser-211, thus
facilitating TFEB activation. Overall, this work identifies a critical mechanism
that activates TFEB and TFE3 without turning off mTORC1 activity. We propose that
this mechanism may enable some cell types such as immune or cancer cells that
require simultaneous TFEB/TFE3 and mTORC1 signaling to survive and achieve robust
cell growth in stressful environments.
PMID- 29945973
TI - Structures of ubiquitin-like (Ubl) and Hsp90-like domains of sacsin provide
insight into pathological mutations.
AB - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a
neurodegenerative disease that is caused by mutations in the SACS gene. The
product of this gene is a very large 520-kDa cytoplasmic protein, sacsin, with a
ubiquitin-like (Ubl) domain at the N terminus followed by three large sacsin
internal repeat (SIRPT) supradomains and C-terminal J and HEPN domains. The
SIRPTs are predicted to contain Hsp90-like domains, suggesting a potential
chaperone activity. In this work, we report the structures of the Hsp90-like Sr1
domain of SIRPT1 and the N-terminal Ubl domain determined at 1.55- and 2.1-A
resolutions, respectively. The Ubl domain crystallized as a swapped dimer that
could be relevant in the context of full-length protein. The Sr1 domain displays
the Bergerat protein fold with a characteristic nucleotide-binding pocket,
although it binds nucleotides with very low affinity. The Sr1 structure reveals
that ARSACS-causing missense mutations (R272H, R272C, and T201K) disrupt protein
folding, most likely leading to sacsin degradation. This work lends structural
support to the view of sacsin as a molecular chaperone and provides a framework
for future studies of this protein.
PMID- 29945975
TI - Untargeted Antifungal Treatment in Nonneutropenic Critically Ill Patients: Should
Further Studies Be Performed Based on Trial Sequential Analysis Results?
PMID- 29945974
TI - High-throughput screening with nucleosome substrate identifies small-molecule
inhibitors of the human histone lysine methyltransferase NSD2.
AB - The histone lysine methyltransferase nuclear receptor-binding SET domain protein
2 (NSD2, also known as WHSC1/MMSET) is an epigenetic modifier and is thought to
play a driving role in oncogenesis. Both NSD2 overexpression and point mutations
that increase its catalytic activity are associated with several human cancers.
Although NSD2 is an attractive therapeutic target, no potent, selective, and
bioactive small molecule inhibitors of NSD2 have been reported to date, possibly
due to the challenges of developing high-throughput assays for NSD2. Here, to
establish a platform for the discovery and development of selective NSD2
inhibitors, we optimized and implemented multiple assays. We performed
quantitative high-throughput screening with full-length WT NSD2 and a nucleosome
substrate against a diverse collection of bioactive small molecules comprising
16,251 compounds. We further interrogated 174 inhibitory compounds identified in
the primary screen with orthogonal and counter assays and with activity assays
based on the clinically relevant NSD2 variants E1099K and T1150A. We selected
five confirmed inhibitors for follow-up, which included a radiolabeled validation
assay, surface plasmon resonance studies, methyltransferase profiling, and
histone methylation in cells. We found that all five NSD2 inhibitors bind the
catalytic SET domain and one exhibited apparent activity in cells, validating the
workflow and providing a template for identifying selective NSD2 inhibitors. In
summary, we have established a robust discovery pipeline for identifying potent
NSD2 inhibitors from small-molecule libraries.
PMID- 29945976
TI - Reply to Cortegiani and Giarratano, "Untargeted Antifungal Treatment in
Nonneutropenic Critically Ill Patients: Should Further Studies Be Performed Based
on Trial Sequential Analysis Results?"
PMID- 29945978
TI - Science and Culture: Math tools send legislators back to the drawing board.
PMID- 29945977
TI - Correction for Pardos de la Gandara et al., "Genetic Determinants of High-Level
Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus".
PMID- 29945981
TI - BMA calls for end to period poverty.
PMID- 29945979
TI - Inner Workings: The race to patch the human heart.
PMID- 29945982
TI - INT-767 prevents NASH and promotes visceral fat brown adipogenesis and
mitochondrial function.
AB - The bile acid receptors, farnesoid X receptor (FXR) and Takeda G-protein-coupled
receptor 5 (TGR5), regulate multiple pathways, including glucose and lipid
metabolism. In a rabbit model of high-fat diet (HFD)-induced metabolic syndrome,
long-term treatment with the dual FXR/TGR5 agonist INT-767 reduces visceral
adipose tissue accumulation, hypercholesterolemia and nonalcoholic
steatohepatitis. INT-767 significantly improves the hallmarks of insulin
resistance in visceral adipose tissue (VAT) and induces mitochondrial and brown
fat-specific markers. VAT preadipocytes isolated from INT-767-treated rabbits,
compared to preadipocytes from HFD, show increased mRNA expression of brown
adipogenesis markers. In addition, INT-767 induces improved mitochondrial
ultrastructure and dynamic, reduced superoxide production and improved insulin
signaling and lipid handling in preadipocytes. Both in vivo and in vitro
treatments with INT-767 counteract, in preadipocytes, the HFD-induced alterations
by upregulating genes related to mitochondrial biogenesis and function. In
preadipocytes, INT-767 behaves mainly as a TGR5 agonist, directly activating dose
dependently the cAMP/PKA pathway. However, in vitro experiments also suggest that
FXR activation by INT-767 contributes to the insulin signaling improvement. INT
767 treatment counteracts HFD-induced liver histological alterations and
normalizes the increased pro-inflammatory genes. INT-767 also induces a
significant reduction of fatty acid synthesis and fibrosis markers, while
increasing lipid handling, insulin signaling and mitochondrial markers. In
conclusion, INT-767 significantly counteracts HFD-induced liver and fat
alterations, restoring insulin sensitivity and prompting preadipocytes
differentiation toward a metabolically healthy phenotype.
PMID- 29945983
TI - Are medical students in prehospital care at risk of moral injury?
AB - BACKGROUND: The term 'moral injury' may be useful in conceptualising the negative
psychological effects of delivering emergency and prehospital medicine as it
provides a non-pathological framework for understanding these effects. This is in
contrast to concepts such as burnout and post-traumatic stress disorder which
suggest practitioners have reached a crisis point. We conducted an exploratory,
pilot study to determine whether the concept of moral injury resonated with
medical students working in emergency medicine and what might mitigate that
injury for them. METHODS: Structured interviews and focus groups were carried out
with medical students involved in the delivery of prehospital and emergency
medicine. The study was carried out at Barts and the London School of Medicine
and Dentistry in May and June 2017. The data were analysed using theoretically
driven thematic analysis. RESULTS: Concepts of moral injury such as witnessing
events which contravene one's moral code, especially those involving children, or
acts of violence, resonated with the experiences of medical students in this
study. Participants stated that having more medical knowledge and a clear sense
of a job to do on scene helped reduce their distress at the time. While social
support was a protective factor, not all students found the process of debrief
easy to access or undergo, those with more established relationships with
colleagues fared better in this regard. CONCLUSIONS: The term moral injury is
useful in exploring the experience of medical students in emergency medicine.
More effort should be made to ensure that students effectively access debrief and
other support opportunities. It is hoped that future work will be undertaken with
different professional groups and explore the potential psychological and
neuropsychological impact of witnessing trauma.
PMID- 29945984
TI - Excess deaths: government commissions review.
PMID- 29945986
TI - Wnt signalling: conquering complexity.
AB - The history of the Wnt pathway is an adventure that takes us from mice and flies
to frogs, zebrafish and beyond, sketching the outlines of a molecular signalling
cascade along the way. Here, we specifically highlight the instrumental role that
developmental biology has played throughout. We take the reader on a journey,
starting with developmental genetics studies that identified some of the main
molecular players, through developmental model organisms that helped unravel
their biochemical function and cell biological activities. Culminating in complex
analyses of stem cell fate and dynamic tissue growth, these efforts beautifully
illustrate how different disciplines provided missing pieces of a puzzle.
Together, they have shaped our mechanistic understanding of the Wnt pathway as a
conserved signalling process in development and disease. Today, researchers are
still uncovering additional roles for Wnts and other members of this multifaceted
signal transduction pathway, opening up promising new avenues for clinical
applications.
PMID- 29945987
TI - Advocating developmental biology.
PMID- 29945985
TI - What does time mean in development?
AB - Biology is dynamic. Timescales range from frenetic sub-second ion fluxes and
enzymatic reactions to the glacial millions of years of evolutionary change.
Falling somewhere in the middle of this range are the processes we usually study
in development: cell division and differentiation, gene expression, cell-cell
signalling, and morphogenesis. But what sets the tempo and manages the order of
developmental events? Are the order and tempo different between species? How is
the sequence of multiple events coordinated? Here, we discuss the importance of
time for developing embryos, highlighting the necessity for global as well as
cell-autonomous control. New reagents and tools in imaging and genomic
engineering, combined with in vitro culture, are beginning to offer fresh
perspectives and molecular insight into the origin and mechanisms of
developmental time.
PMID- 29945989
TI - Philosophical medical ethics: more necessary than ever.
PMID- 29945988
TI - Third-generation in situ hybridization chain reaction: multiplexed, quantitative,
sensitive, versatile, robust.
AB - In situ hybridization based on the mechanism of the hybridization chain reaction
(HCR) has addressed multi-decade challenges that impeded imaging of mRNA
expression in diverse organisms, offering a unique combination of multiplexing,
quantitation, sensitivity, resolution and versatility. Here, with third
generation in situ HCR, we augment these capabilities using probes and amplifiers
that combine to provide automatic background suppression throughout the protocol,
ensuring that reagents will not generate amplified background even if they bind
non-specifically within the sample. Automatic background suppression dramatically
enhances performance and robustness, combining the benefits of a higher signal-to
background ratio with the convenience of using unoptimized probe sets for new
targets and organisms. In situ HCR v3.0 enables three multiplexed quantitative
analysis modes: (1) qHCR imaging - analog mRNA relative quantitation with
subcellular resolution in the anatomical context of whole-mount vertebrate
embryos; (2) qHCR flow cytometry - analog mRNA relative quantitation for high
throughput expression profiling of mammalian and bacterial cells; and (3) dHCR
imaging - digital mRNA absolute quantitation via single-molecule imaging in thick
autofluorescent samples.
PMID- 29945990
TI - Guest editorial: Charlie Gard's five months in court: better dispute resolution
mechanisms for medical futility disputes.
PMID- 29945991
TI - Talazoparib Is a Potent Radiosensitizer in Small Cell Lung Cancer Cell Lines and
Xenografts.
AB - Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with a
critical need for novel therapies. Our goal was to determine whether PARP
inhibition could sensitize SCLC cells to ionizing radiation (IR) and if so, to
determine the contribution of PARP trapping to radiosensitization.Experimental
Design: Short-term viability assays and clonogenic survival assays (CSA) were
used to assess radiosensitization in 6 SCLC cell lines. Doses of veliparib and
talazoparib with equivalent enzymatic inhibitory activity but differing PARP
trapping activity were identified and compared in CSAs. Talazoparib, IR, and
their combination were tested in three patient-derived xenograft (PDX)
models.Results: Talazoparib radiosensitized 5 of 6 SCLC cell lines in short-term
viability assays and confirmed in 3 of 3 cell lines by CSAs. Concentrations of
200 nmol/L talazoparib and 1,600 nmol/L veliparib similarly inhibited PAR
polymerization; however, talazoparib exhibited greater PARP trapping activity
that was associated with superior radiosensitization. This observation further
correlated with an increased number of double-stranded DNA breaks induced by
talazoparib as compared with veliparib. Finally, a dose of 0.2 mg/kg talazoparib
in vivo caused tumor growth inhibition in combination with IR but not as a single
agent in 3 SCLC PDX models.Conclusions: PARP inhibition effectively sensitizes
SCLC cell lines and PDXs to IR, and PARP trapping activity enhances this effect.
PARP inhibitors, especially those with high PARP trapping activity, may provide a
powerful tool to improve the efficacy of radiotherapy in SCLC. Clin Cancer Res;
24(20); 5143-52. (c)2018 AACR.
PMID- 29945993
TI - The Integration of Radiotherapy with Immunotherapy for the Treatment of Non-Small
Cell Lung Cancer.
AB - Five-year survival rates for non-small cell lung cancer (NSCLC) range from 14% to
49% for stage I to stage IIIA disease, and are <5% for stage IIIB/IV disease.
Improvements have been made in the outcomes of patients with NSCLC due to
advancements in radiotherapy (RT) techniques, the use of concurrent chemotherapy
with RT, and the emergence of immunotherapy as first- and second-line treatment
in the metastatic setting. RT remains the mainstay treatment in patients with
inoperable early-stage NSCLC and is given concurrently or sequentially with
chemotherapy in patients with locally advanced unresectable disease. There is
emerging evidence that RT not only provides local tumor control but also may
influence systemic control. Multiple preclinical studies have demonstrated that
RT induces immunomodulatory effects in the local tumor microenvironment,
supporting a synergistic combination approach with immunotherapy to improve
systemic control. Immunotherapy options that could be combined with RT include
programmed cell death-1/programmed cell death ligand-1 blockers, as well as
investigational agents such as OX-40 agonists, toll-like receptor agonists,
indoleamine 2,3-dioxygenase-1 inhibitors, and cytokines. Here, we describe the
rationale for the integration of RT and immunotherapy in patients with NSCLC,
present safety and efficacy data that support this combination strategy, review
planned and ongoing studies, and highlight unanswered questions and future
research needs.
PMID- 29945992
TI - Endoglin Expression on Cancer-Associated Fibroblasts Regulates Invasion and
Stimulates Colorectal Cancer Metastasis.
AB - Purpose: Cancer-associated fibroblasts (CAF) are a major component of the
colorectal cancer tumor microenvironment. CAFs play an important role in tumor
progression and metastasis, partly through TGF-beta signaling pathway. We
investigated whether the TGF-beta family coreceptor endoglin is involved in CAF
mediated invasion and metastasis.Experimental Design: CAF-specific endoglin
expression was studied in colorectal cancer resection specimens using IHC and
related to metastases-free survival. Endoglin-mediated invasion was assessed in
vitro by transwell invasion, using primary colorectal cancer-derived CAFs.
Effects of CAF-specific endoglin expression on tumor cell invasion were
investigated in a colorectal cancer zebrafish model, whereas liver metastases
were assessed in a mouse model.Results: CAFs specifically at invasive borders of
colorectal cancer express endoglin and increased expression intensity correlated
with increased disease stage. Endoglin-expressing CAFs were also detected in
lymph node and liver metastases, suggesting a role in colorectal cancer
metastasis formation. In stage II colorectal cancer, CAF-specific endoglin
expression at invasive borders correlated with poor metastasis-free survival. In
vitro experiments revealed that endoglin is indispensable for bone morphogenetic
protein (BMP)-9-induced signaling and CAF survival. Targeting endoglin using the
neutralizing antibody TRC105 inhibited CAF invasion in vitro In zebrafish,
endoglin-expressing fibroblasts enhanced colorectal tumor cell infiltration into
the liver and decreased survival. Finally, CAF-specific endoglin targeting with
TRC105 decreased metastatic spread of colorectal cancer cells to the mouse
liver.Conclusions: Endoglin-expressing CAFs contribute to colorectal cancer
progression and metastasis. TRC105 treatment inhibits CAF invasion and tumor
metastasis, indicating an additional target beyond the angiogenic endothelium,
possibly contributing to beneficial effects reported during clinical evaluations.
Clin Cancer Res; 24(24); 1-14. (c)2018 AACR.
PMID- 29945994
TI - Clonal Structures of Regionally Synchronous Gastric Adenomas and Carcinomas.
AB - Purpose: Gastric adenoma (GA) is a premalignant lesion that precedes intestinal
type gastric carcinoma (GC). However, genetic progression mechanisms from GA to
GC have not been clarified.Experimental Design: We performed whole-exome
sequencing-based mutational analyses for 15 synchronous pairs of attached GAs and
GCs.Results: There was no significant difference in the number of driver
mutations or copy-number alterations between GAs and GCs. Well-known mutations of
TP53, APC, RNF43, and RPL22 were recurrently detected in synchronous GA/GC pairs.
In addition, we discovered novel KDM6A, PREX2, FAT1, KMT2C, GLI3, and RPL22
mutations and hypermutation in GAs, but did not identify recurrent drivers for GA
to-GC progression. Clonal structure analyses revealed that most GA/GC pairs
exhibit parallel evolution with early divergence rather than stepwise evolution
during GA-to-GC progression. Of note, three cases were identified as clonally
nonrelated GA/GC pairs despite the lack of histologic differences. We found
differences in dominant mutational signatures 1, 6, 15, and 17 in GA/GC trunks,
GA branches, and GC branches. Compared with our previous work on synchronous
colon adenoma/carcinoma genome structures, where most drivers were in the trunk
with parallel evolution, synchronous GA/GC genomes showed a different model of
parallel evolution, with many drivers in the branches.Conclusions: The preferred
sequence of mutational events during GA-to-GC progression might be more context
dependent than colon adenoma progression. Our results show that nonclonal
synchronous GA/GC is common and that GA genomes have already acquired distinct
genomic alterations, suggesting caution in the diagnosis of synchronous GA and
GC, especially in residual or recurrent cases. Clin Cancer Res; 24(19); 4715-25.
(c)2018 AACR.
PMID- 29945995
TI - Characterization of Alternative Splicing Events in HPV-Negative Head and Neck
Squamous Cell Carcinoma Identifies an Oncogenic DOCK5 Variant.
AB - Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most common
cancers worldwide, and alternative splicing is considered to play important roles
in tumor progression. Our study is designed to identify alternative splicing
events (ASEs) in human papillomavirus (HPV)-negative HNSCC.Experimental Design:
RNA sequencing data of 407 HPV-negative HNSCC and 38 normal samples were obtained
from The Cancer Genome Atlas (TCGA), and splice junctions were discovered using
MapSplice. Outlier analysis was used to identify significant splicing junctions
between HPV-negative HNSCC and normal samples. To explore the functional role of
the identified DOCK5 variant, we checked its expression with qRT-PCR in a
separate primary tumor validation set and performed proliferation, migration, and
invasion assays.Results: A total of 580 significant splicing events were
identified in HPV-negative HNSCC, and the most common type of splicing events was
an alternative start site (33.3%). The prevalence of a given individual ASE among
the tumor cohort ranged from 9.8% and 64.4%. Within the 407 HPV-negative HNSCC
samples in TCGA, the number of significant ASEs differentially expressed in each
tumor ranged from 17 to 290. We identified a novel candidate oncogenic DOCK5
variant confirmed using qRT-PCR in a separate primary tumor validation set. Loss-
and gain-of-function experiments indicated that DOCK5 variant promoted
proliferation, migration, and invasion of HPV-negative HNSCC cells, and patients
with higher expression of DOCK5 variant showed decreased overall
survival.Conclusions: Analysis of ASEs in HPV-negative HNSCC identifies multiple
alterations likely related to carcinogenesis, including an oncogenic DOCK5
variant. Clin Cancer Res; 24(20); 5123-32. (c)2018 AACR.
PMID- 29945996
TI - The Light Chain IgLV3-21 Defines a New Poor Prognostic Subgroup in Chronic
Lymphocytic Leukemia: Results of a Multicenter Study.
AB - Purpose: Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status
or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic
leukemia (CLL) patients. Interestingly, IgHV3-21 is often co-expressed with light
chain IgLV3-21, which is potentially able to trigger cell-autonomous BCR-mediated
signaling. However, this light chain has never been characterized independently
of the heavy chain IgHV3-21.Experimental Design: We performed total RNA
sequencing in 32 patients and investigated IgLV3-21 prognostic impact in terms of
treatment-free survival (TFS) and overall survival (OS) in 3 other independent
cohorts for a total of 813 patients. IgLV3-21 presence was tested by real-time
PCR and confirmed by Sanger sequencing.Results: Using total RNA sequencing to
characterize 32 patients with high-risk CLL, we found a high frequency (28%) of
IgLV3-21 rearrangements. Gene set enrichment analysis revealed that these
patients express higher levels of genes responsible for ribosome biogenesis and
translation initiation (P < 0.0001) as well as MYC target genes (P = 0.0003).
Patients with IgLV3-21 rearrangements displayed a significantly shorter TFS and
OS (P < 0.05), particularly those with IgHV mutation. In each of the three
independent validation cohorts, we showed that IgLV3-21 rearrangements-similar to
UM IgHV status-conferred poor prognosis compared with mutated IgHV (P < 0.0001).
Importantly, we confirmed by multivariate analysis that this was independent of
IgHV mutational status or subset #2 stereotyped receptor (P <
0.0001).Conclusions: We have demonstrated for the first time that a light chain
can affect CLL prognosis and that IgLV3-21 light chain usage defines a new
subgroup of CLL patients with poor prognosis. Clin Cancer Res; 24(20); 5048-57.
(c)2018 AACR.
PMID- 29945997
TI - Assessing Therapeutic Efficacy of MEK Inhibition in a KRASG12C-Driven Mouse Model
of Lung Cancer.
AB - Purpose: Despite the challenge to directly target mutant KRAS due to its high GTP
affinity, some agents are under development against downstream signaling
pathways, such as MEK inhibitors. However, it remains controversial whether MEK
inhibitors can boost current chemotherapy in KRAS-mutant lung tumors in clinic.
Considering the genomic heterogeneity among patients with lung cancer, it is
valuable to test potential therapeutics in KRAS mutation-driven mouse
models.Experimental Design: We first compared the pERK1/2 level in lung cancer
samples with different KRAS substitutions and generated a new genetically
engineered mouse model whose tumor was driven by KRAS G12C, the most common KRAS
mutation in lung cancer. Next, we evaluated the efficacy of selumetinib or its
combination with chemotherapy, in KRASG12C tumors compared with KRASG12D tumors.
Moreover, we generated KRASG12C/p53R270H model to explore the role of a dominant
negative p53 mutation detected in patients in responsiveness to MEK
inhibition.Results: We determined higher pERK1/2 in KRASG12C lung tumors compared
with KRASG12D Using mouse models, we further identified that KRASG12C tumors are
significantly more sensitive to selumetinib compared with KrasG12D tumors. MEK
inhibition significantly increased chemotherapeutic efficacy and progression-free
survival of KRASG12C mice. Interestingly, p53 co-mutation rendered KRASG12C lung
tumors less sensitive to combination treatment with selumetinib and
chemotherapy.Conclusions: Our data demonstrate that unique KRAS mutations and
concurrent mutations in tumor-suppressor genes are important factors for lung
tumor responses to MEK inhibitor. Our preclinical study supports further clinical
evaluation of combined MEK inhibition and chemotherapy for lung cancer patients
harboring KRAS G12C and wild-type p53 status. Clin Cancer Res; 24(19); 4854-64.
(c)2018 AACR.
PMID- 29945999
TI - TRIMming TGF-beta signals in Th17 cells.
AB - The precise downstream mediators of TGF-beta signaling in Th17 and T reg cells
remain unclear. In this issue of JEM, Tanaka et al. report that Trim33 transduces
TGF-beta signals in Th17 cells to generate an optimal proinflammatory cytokine
profile.
PMID- 29945998
TI - Molecular Analyses Support the Safety and Activity of Retroviral Replicating
Vector Toca 511 in Patients.
AB - Purpose: Toca 511 is a gammaretroviral replicating vector encoding cytosine
deaminase that selectively infects tumor cells and converts the antifungal drug 5
fluorocytosine into the antineoplastic drug 5-fluorouracil, which directly kills
tumor cells and stimulates antitumor immune responses. As part of clinical
monitoring of phase I clinical trials in recurrent high-grade glioma, we have
performed extensive molecular analyses of patient specimens to track vector
fate.Patients and Methods: Toca 511 and Toca FC (extended-release 5
fluorocytosine) have been administered to 127 high-grade glioma patients across
three phase I studies. We measured Toca 511 RNA and DNA levels in available body
fluids and tumor samples from patients to assess tumor specificity. We mapped
Toca 511 integration sites and sequenced integrated Toca 511 genomes from patient
samples with detectable virus. We measured Toca 511 levels in a diverse set of
tissue samples from one patient.Results: Integrated Toca 511 is commonly detected
in tumor samples and is only transiently detected in blood in a small fraction of
patients. There was no believable evidence for clonal expansion of cells with
integrated Toca 511 DNA, or preferential retrieval of integration sites near
oncogenes. Toca 511 sequence profiles suggest most mutations are caused by APOBEC
cytidine deaminases acting during reverse transcription. Tissue samples from a
single whole-body autopsy affirm Toca 511 tumor selectivity.Conclusions: Toca 511
and Toca FC treatment was not associated with inappropriate integration sites and
clonal expansion. The vector is tumor-selective and persistent in patients who
received Toca 511 injections. Clin Cancer Res; 24(19); 4680-93. (c)2018 AACR.
PMID- 29946000
TI - Ca2+-mitochondria axis drives cell division in hematopoietic stem cells.
AB - Most of the hematopoietic stem cells (HSCs) within the bone marrow (BM) show
quiescent state with a low mitochondrial membrane potential (DeltaPsim). In
contrast, upon stress hematopoiesis, HSCs actively start to divide. However, the
underlying mechanism for the initiation of HSC division still remains unclear. To
elucidate the mechanism underlying the transition of cell cycle state in HSCs, we
analyzed the change of mitochondria in HSCs after BM suppression induced by 5
fluoruracil (5-FU). We found that HSCs initiate cell division after exhibiting
enhanced DeltaPsim as a result of increased intracellular Ca2+ level. Although
further activation of Ca2+-mitochondria pathway led to loss of HSCs after cell
division, the appropriate suppression of intracellular Ca2+ level by exogenous
adenosine or Nifedipine, a Ca2+ channel blocker, prolonged cell division interval
in HSCs, and simultaneously achieved both cell division and HSC maintenance.
Collectively, our results indicate that the Ca2+-mitochondria pathway induces HSC
division critically to determine HSC cell fate.
PMID- 29946001
TI - Development and validation of a radiological diagnosis model for hypersensitivity
pneumonitis.
AB - High-resolution computed tomography (HRCT) may be useful for diagnosing
hypersensitivity pneumonitis. Here, we develop and validate a radiological
diagnosis model and model-based points score.Patients with interstitial lung
disease seen at the University of Michigan Health System (derivation cohort) or
enrolling in the Lung Tissue Research Consortium (validation cohort) were
included. A thin-section, inspiratory HRCT scan was required. Thoracic
radiologists documented radiological features.The derivation cohort comprised 356
subjects (33.9% hypersensitivity pneumonitis) and the validation cohort comprised
424 subjects (15.5% hypersensitivity pneumonitis). An age-, sex- and smoking
status-adjusted logistic regression model identified extent of mosaic attenuation
or air trapping greater than that of reticulation ("MA-AT>Reticulation"; OR 6.20,
95% CI 3.53-10.90; p<0.0001) and diffuse axial disease distribution (OR 2.33, 95%
CI 1.31-4.16; p=0.004) as hypersensitivity pneumonitis predictors (area under the
receiver operating characteristic curve 0.814). A model-based score >2 (1 point
for axial distribution, 2 points for "MA-AT>Reticulation") has specificity 90%
and positive predictive value (PPV) 74% in the derivation cohort and specificity
96% and PPV 44% in the validation cohort. Similar model performance is seen with
population restriction to those reporting no exposure (score >2: specificity
91%).When radiological mosaic attenuation or air trapping are more extensive than
reticulation and disease has diffuse axial distribution, hypersensitivity
pneumonitis specificity is high and false diagnosis risk low (<10%), but PPV is
diminished in a low-prevalence setting.
PMID- 29946002
TI - Profiling of healthy and asthmatic airway smooth muscle cells following
interleukin-1beta treatment: a novel role for CCL20 in chronic mucus
hypersecretion.
AB - Chronic mucus hypersecretion (CMH) contributes to the morbidity and mortality of
asthma, and remains uncontrolled by current therapies in the subset of patients
with severe, steroid-resistant disease. Altered cross-talk between airway
epithelium and airway smooth muscle cells (ASMCs), driven by pro-inflammatory
cytokines such as interleukin (IL)-1beta, provides a potential mechanism that
influences CMH. This study investigated mechanisms underlying CMH by comparing IL
1beta-induced gene expression profiles between asthma and control-derived ASMCs
and the subsequent paracrine influence on airway epithelial mucus production in
vitroIL-1beta-treated ASMCs from asthmatic patients and healthy donors were
profiled using microarray analysis and ELISA. Air-liquid interface (ALI)-cultured
CALU-3 and primary airway epithelial cells were treated with identified
candidates and mucus production assessed.The IL-1beta-induced CCL20 expression
and protein release was increased in ASMCs from moderate compared with mild
asthmatic patients and healthy controls. IL-1beta induced lower MIR146A
expression in asthma-derived ASMCs compared with controls. Decreased MIR146A
expression was validated in vivo in bronchial biopsies from 16 asthmatic patients
versus 39 healthy donors. miR-146a-5p overexpression abrogated CCL20 release in
ASMCs. CCL20 treatment of ALI-cultured CALU-3 and primary airway epithelial cells
induced mucus production, while CCL20 levels in sputum were associated with
increased levels of CMH in asthmatic patients.Elevated CCL20 production by ASMCs,
possibly resulting from dysregulated expression of the anti-inflammatory miR-146a
5p, may contribute to enhanced mucus production in asthma.
PMID- 29946003
TI - Impact of turnaround time on outcome with point-of-care testing for respiratory
viruses: a post hoc analysis from a randomised controlled trial.
PMID- 29946004
TI - Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder
disease: a multisite study.
AB - Anaerobic and aerobic bacteria were quantitated in respiratory samples across
three cystic fibrosis (CF) centres using extended culture methods. Subjects aged
1-69 years who were clinically stable provided sputum (n=200) or bronchoalveolar
lavage (n=55). 18 anaerobic and 39 aerobic genera were cultured from 59% and 95%
of samples, respectively; 16 out of 57 genera had a >=5% prevalence across
centres.Analyses of microbial communities using co-occurrence networks in sputum
samples showed groupings of oral, including anaerobic, bacteria, whereas typical
CF pathogens formed distinct entities. Pseudomonas was associated with worse
nutrition and F508del genotype, whereas anaerobe prevalence was positively
associated with pancreatic sufficiency, better nutrition and better lung
function. A higher total anaerobe/total aerobe CFU ratio was associated with
pancreatic sufficiency and better nutrition. Subjects grouped by factor analysis
who had relative dominance of anaerobes over aerobes had milder disease compared
with a Pseudomonas-dominated group with similar proportions of subjects that were
homozygous for F508del.In summary, anaerobic bacteria occurred at an early age.
In sputum-producing subjects anaerobic bacteria were associated with milder
disease, suggesting that targeted eradication of anaerobes may not be warranted
in sputum-producing CF subjects.
PMID- 29946005
TI - Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary
fibrosis.
AB - We assessed safety and tolerability of treatment with pirfenidone (1602-2403
mg.day-1) and nintedanib (200-300 mg.day-1) in patients with idiopathic pulmonary
fibrosis (IPF).This 24-week, single-arm, open-label, phase IV study
(ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with
forced vital capacity % pred >=50% and diffusing capacity of the lung for carbon
monoxide % pred >=30%. Before initiating nintedanib, patients had received
pirfenidone for >=16 weeks and tolerated a stable dose of >=1602 mg.day-1 for
>=28 days. The primary end-point was the proportion of patients who completed 24
weeks of combination treatment on pirfenidone (1602-2403 mg.day-1) and nintedanib
(200-300 mg.day-1). Investigators recorded treatment-emergent adverse events
(TEAEs), attributing them to pirfenidone, nintedanib, both or neither.89 patients
were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end
point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients
had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the
most common. Two patients had serious treatment-related TEAEs.Combined
pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of
patients with IPF and associated with a similar pattern of TEAEs expected for
either treatment alone. These results encourage further study of combination
treatment with pirfenidone and nintedanib in patients with IPF.
PMID- 29946006
TI - Serotonergic antidepressant use and morbidity and mortality among older adults
with COPD.
AB - We evaluated the relationship between new selective serotonin reuptake inhibitor
(SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI) drug use and
respiratory-related morbidity and mortality among older adults with chronic
obstructive pulmonary disease (COPD).This was a retrospective population-based
cohort study using heath administrative data from Ontario, Canada. Individuals
aged >=66 years, with validated, physician-diagnosed COPD (n=131 718) were
included. New SSRI/SNRI users were propensity score matched 1:1 to controls on 40
relevant covariates to minimise potential confounding.Among propensity score
matched community-dwelling individuals, new SSRI/SNRI users compared to non-users
had significantly higher rates of hospitalisation for COPD or pneumonia (hazard
ratio (HR) 1.15, 95% CI 1.05-1.25), emergency room visits for COPD or pneumonia
(HR 1.13, 95% CI 1.03-1.24), COPD or pneumonia-related mortality (HR 1.26, 95% CI
1.03-1.55) and all-cause mortality (HR 1.20, 95% CI 1.11-1.29). In addition,
respiratory-specific and all-cause mortality rates were higher among long-term
care home residents newly starting SSRI/SNRI drugs versus controls.New use of
serotonergic antidepressants was associated with small, but significant,
increases in rates of respiratory-related morbidity and mortality among older
adults with COPD. Further research is needed to clarify if the observed
associations are causal or instead reflect unresolved confounding.
PMID- 29946007
TI - Stability or improvement in forced vital capacity with nintedanib in patients
with idiopathic pulmonary fibrosis.
AB - In the Phase III INPULSIS(r) trials, nintedanib reduced the annual rate of
decline in forced vital capacity (FVC) versus placebo in patients with idiopathic
pulmonary fibrosis (IPF).We conducted post hoc analyses of the distribution of
changes in FVC in the INPULSIS(r) trials and FVC changes in the open-label
extension trial INPULSIS(r)-ON in subgroups of patients based on whether patients
had shown an improvement or no decline in FVC in INPULSIS(r). Analyses were
descriptive.Based on the annual rate of change in FVC, 158 of 638 patients
(24.8%) treated with nintedanib and 38 of 423 patients (9.0%) treated with
placebo had an improvement/no decline in FVC in the INPULSIS(r) trials. In
patients whose FVC improved/did not decline, median (interquartile range)
improvements in FVC at week 52 were 76.5 (31-152) mL and 57.5 (31-103) mL in the
nintedanib and placebo groups, respectively. Changes in FVC from baseline to week
48 of INPULSIS(r)-ON were similar in patients whose FVC improved or declined in
the preceding INPULSIS(r) trial.In the INPULSIS(r) trials, treatment with
nintedanib resulted in a greater proportion of patients with IPF showing an
improvement/no decline in FVC compared to taking placebo. Mechanisms underlying
improvement in FVC in patients with IPF are unknown.
PMID- 29946008
TI - Prevalence, characteristics and management of frequently exacerbating asthma
patients: an observational study in Sweden (PACEHR).
AB - The aim of the study was to investigate the prevalence, management and
characteristics of asthma patients with frequent exacerbations.Data from asthma
patients (aged >=18 years) identified in primary care medical records were linked
to Swedish national health registries. Exacerbations were defined as
hospitalisations, emergency visits and/or collection of oral steroids. Frequent
exacerbations were defined as two or more exacerbations per year during the 3
year observation period.Of 18 724 asthma patients, 81.49% had no exacerbations
and 6.3% had frequent exacerbations in the year prior to the index date. Frequent
exacerbations were observed yearly for 1.8% of the patients. Frequent
exacerbators were older, more often females, and had increased eosinophil and
neutrophil counts, lower lung function, and more comorbidities than patients
without exacerbations. There was a slight increase in asthma medication claims
and a slight decrease in physician visits compared with baseline, both in the
group with and the group without frequent exacerbations.Patients with frequent
exacerbations were characterised by greater age, female predominance, high
eosinophil and neutrophil counts, and high prevalence of comorbidities. This
study indicates that the Swedish healthcare system lacks efficiency to adjust
treatment and management for this patient group. With new treatment options
targeting severe asthma available, identification of these patients should be in
focus to ensure reduction of exacerbations.
PMID- 29946009
TI - Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages
in ARDS.
AB - Exaggerated release of neutrophil extracellular traps (NETs) along with decreased
NET clearance and inability to remove apoptotic cells (efferocytosis) may
contribute to sustained inflammation in acute respiratory distress syndrome
(ARDS). Recent studies in experimental models of ARDS have revealed the crosstalk
between AMP-activated protein kinase (AMPK) and high-mobility group box 1
(HMGB1), which may contribute to effectiveness of efferocytosis, thereby reducing
inflammation and ARDS severity.We investigated neutrophil and NET clearance by
macrophages from control and ARDS patients and examined how bronchoalveolar
lavage (BAL) fluid from control and ARDS patients could affect NET formation and
efferocytosis. Metformin (an AMPK activator) and neutralising antibody against
HMGB1 were applied to improve efferocytosis and NET clearance.Neutrophils from
ARDS patients showed significantly reduced apoptosis. Conversely, NET formation
was significantly enhanced in ARDS patients. Exposure of neutrophils to ARDS BAL
fluid promoted NET production, while control BAL fluid had no effect. Macrophage
engulfment of NETs and apoptotic neutrophils was diminished in ARDS patients.
Notably, activation of AMPK in macrophages or neutralisation of HMGB1 in BAL
fluid improved efferocytosis and NET clearance.In conclusion, restoration of AMPK
activity with metformin or specific neutralisation of HMGB1 in BAL fluid
represent promising therapeutic strategies to decrease sustained lung
inflammation during ARDS.
PMID- 29946010
TI - Familial aggregation and heritability of sarcoidosis: a Swedish nested case
control study.
AB - Sarcoidosis is believed to be caused by both genetic and environmental risk
factors, but the proportion of the susceptibility to sarcoidosis that is mediated
by genetics remains unknown. We aimed to estimate the familial aggregation and
heritability of sarcoidosis using a case-control-family study design and
population-based Swedish registers.We identified 23 880 individuals with visits
for sarcoidosis in the Swedish National Patient Register using International
Classification of Diseases codes (1964-2013). Information on Lofgren's syndrome
was available for a subset diagnosed at Karolinska University Hospital
(Stockholm, Sweden). General population controls were matched to cases (10:1).
Relatives of cases and controls were identified from the Swedish Multi-Generation
Register and ascertained for sarcoidosis in the National Patient Register. We
estimated familial relative risks for sarcoidosis using conditional logistic
regression and heritability using biometric models.Having at least one first
degree relative with sarcoidosis was associated with a 3.7-fold increase in the
risk of sarcoidosis (95% CI 3.4-4.1). The relative risk increased in those with
two or more relatives (relative risk 4.7) and in Lofgren's syndrome (relative
risk 4.1). The heritability was 39% (95% CI 12-65%).This large investigation
showed that having a relative with sarcoidosis is a very strong risk factor for
the disease. Genetic variation is an important, albeit partial, contributing
factor to the risk for sarcoidosis.
PMID- 29946011
TI - Variance of Imaging Protocols for Patients With Suspected Acute Ischemic Stroke
Because of Large-Vessel Occlusion.
PMID- 29946012
TI - Call for Basic Science Papers.
PMID- 29946013
TI - Anemia After Aneurysmal Subarachnoid Hemorrhage Is Associated With Poor Outcome
and Death.
AB - Background and Purpose- Anemia after aneurysmal subarachnoid hemorrhage is common
and potentially modifiable. Here, we first evaluate the effect of anemia on
neurological outcome and death and second, study the effects of packed red blood
cell transfusion on outcome. Methods- A secondary analysis on 413 subjects in the
CONSCIOUS-1 study (Clazosentan to Overcome Neurological Ischemia and Infarction
Occurring After Subarachnoid Hemorrhage). Multivariable logistic regression
identified independent risk factors for anemia and determined the effect of
anemia on neurological outcome and death, while adjusting for selected
covariates. Optimal predictive thresholds for hemoglobin levels were determined
using receiver operating characteristic curve analysis. Finally, patients were
pseudorandomized to transfusion using propensity score matching to study the
effect of transfusions on outcome. Results- Anemia, defined as hemoglobin <10
g/dL, was present in 5% of patients at presentation, in 29% of patients after
aneurysm securing (days 1-3), and in 32% of patients during the peak delayed
cerebral ischemia risk period (days 5-9). Anemia after aneurysm securing (odds
ratio, 1.96; 95% confidence interval, 1.07-3.59; P=0.03) and during the delayed
cerebral ischemia window (odds ratio, 2.63; 95% confidence interval, 1.46-4.76;
P=0.0014) was independently associated with poor neurological outcome. Anemia
postaneurysm securing (odds ratio, 3.50; 95% confidence interval, 1.15-10.62;
P=0.027) but not during the delayed cerebral ischemia window was associated with
death. Using propensity score-matched cohorts, we found that transfusion of
anemic patients did not improve long-term outcome (P=0.8) or mortality rates
(P=0.9). Transfusion of patients with a hemoglobin concentration >10 g/dL was
associated with improved neurological outcomes (odds ratio, 0.09; 95% confidence
interval, 0.002-0.72; P=0.015), with no differences in mortality. Conclusions-
Anemia after aneurysmal subarachnoid hemorrhage is associated with poor long-term
neurological outcome and death. Transfusion of packed red blood cells is
beneficial for patients who are not considerably anemic beforehand, suggesting
further work needs to define the threshold but also the time period of anemia
that is sufficient and necessary to contribute to poor outcomes. Clinical Trial
Registration- URL: https://www.clinicaltrials.gov . Unique identifier:
NCT00111085.
PMID- 29946014
TI - Association Between Possible Osteoporosis and Shunt-Dependent Hydrocephalus After
Subarachnoid Hemorrhage.
AB - Background and Purpose- Pathological obstruction in arachnoid granulations after
subarachnoid hemorrhage (SAH) can impede cerebrospinal fluid flow outward to the
venous sinus and causing hydrocephalus. Because bone and arachnoid granulations
share the same collagen type, we evaluated the possible relation between bone
mineral density and shunt-dependent hydrocephalus after SAH. Methods- We measured
Hounsfield units of the frontal skull on admission brain computed tomography in
patients with SAH. Receiver operating characteristic curve analysis was performed
to determine the optimal cutoff Hounsfield unit in skull to predict osteopenia
and osteoporosis in a large sample registry. According to the optimal cutoff
skull Hounsfield unit values, study patients were then categorized as
hypothetical normal, osteopenia, and osteoporosis. Odds ratios were estimated
using logistic regression to determine whether the osteoporotic conditions are
independent predictive factors for the development of shunt-dependent
hydrocephalus after clipping for SAH. Results- A total of 447 patients (alive
>=14 days) with ruptured aneurysm SAH who underwent surgical clipping were
retrospectively enrolled in this study during a 9-year period from 2 hospitals.
We found that hypothetical osteoporosis was an independent predictor for shunt
dependent hydrocephalus after aneurysmal clipping for SAH after full adjustment
for other predictive factors, including age (odds ratio, 2.08; 95% confidence
interval, 1.06-4.08; P=0.032). Conclusions- Our study demonstrates a possible
relation between possible osteoporosis and hydrocephalus after SAH. Hounsfield
unit measurement on admission brain computed tomography may be helpful for
predicting hydrocephalus during the clinical course of SAH in patients with
osteoporosis or suspected osteoporosis.
PMID- 29946015
TI - Association of the Affordable Care Act's Medicaid Expansion With Care Quality and
Outcomes for Low-Income Patients Hospitalized With Heart Failure.
AB - BACKGROUND: Heart failure (HF) is the leading cause of morbidity and mortality in
the United States. Despite advancement in the management of HF, outcomes remain
suboptimal, particularly among the uninsured. In 2014, the Affordable Care Act
expanded Medicaid eligibility, and millions of low-income adults gained
insurance. Little is known about Medicaid expansion's effect on inpatient HF
care. METHODS AND RESULTS: We used the American Heart Association's Get With The
Guidelines-Heart Failure registry to assess changes in inpatient care quality and
outcomes among low-income patients (<65 years old) hospitalized for HF after
Medicaid expansion, in expansion, and nonexpansion states. Patients were
classified as low-income if covered by Medicaid, uninsured, or missing insurance.
Expansion states were those that implemented expansion in 2014. Piecewise
logistic multivariable regression models were constructed to track quarterly
trends of quality and outcome measures in the pre (January 1, 2010-December 31,
2013) and postexpansion (January 1, 2014-June 30, 2017) periods. These measures
were compared between expansion versus nonexpansion states during the
postexpansion period. The cohort included 58 804 patients hospitalized across 391
sites. In states that expanded Medicaid, uninsured HF hospitalizations declined
from 7.9% to 4.4%, and Medicaid HF hospitalizations increased from 18.3% to
34.6%. Defect-free HF care was increasing during the preexpansion period
(adjusted odds ratio/quarter, 1.06; 95% confidence interval, 1.03-1.08) but did
not change after expansion (adjusted odds ratio, 0.99; 95% confidence interval,
0.97-1.02). Patterns were similar for other quality measures. There were no
quality measures for which the rate of improvement sped up after expansion. In
hospital mortality rates remained similar during the preexpansion (adjusted odds
ratio, 0.99; 95% confidence interval, 0.96-1.02) and postexpansion periods
(adjusted odds ratio, 1.00; 95% confidence interval, 0.97-1.03). Among
nonexpansion states, uninsured HF hospitalizations increased (11.6% to 16.7%) as
did Medicaid HF hospitalizations (17.9% to 26.6%), and no quarterly improvement
was observed for most quality measures in the post compared with preexpansion
period. During the postexpansion period, defect-free care and mortality did not
differ between expansion and nonexpansion states. CONCLUSIONS: Medicaid expansion
was associated with a significant decline in uninsured HF hospitalizations but
not improvements in quality of care or in-hospital mortality among sites
participating in a national quality improvement initiative. Efforts beyond
insurance expansion are needed to improve in-hospital outcomes for low-income
patients with HF.
PMID- 29946016
TI - Reasonable disagreement and the justification of pre-emptive ethics governance in
social research: a response to Hammersley.
AB - In this response, we first tackle what we take to be the core disagreement
between ourselves and Hammersley, namely the justification for our model of
social research ethics governance. We then consider what follows from our defence
of governance for ethics review and show how these claims attend to the specific
concerns outlined by Hammersley.
PMID- 29946017
TI - The virtuous self-tolerance of virtual memory T cells.
PMID- 29946019
TI - Patient safety is compromised by understaffing, physicians warn.
PMID- 29946018
TI - Digalactosyldiacylglycerol Is Essential for Organization of the Membrane
Structure in Etioplasts.
AB - Angiosperms germinated in the dark develop etioplasts, the chloroplast
precursors, in cotyledon cells. Etioplasts contain lattice membrane structures
called prolamellar bodies (PLBs) and lamellar prothylakoids as internal membrane
systems. PLBs accumulate the chlorophyll intermediate protochlorophyllide
(Pchlide) in a complex with NADPH and light-dependent NADPH:Pchlide
oxidoreductase (LPOR). Two galactolipids, monogalactosyldiacylglycerol and
digalactosyldiacylglycerol (DGDG), are major constituents of etioplast membranes.
We previously reported that monogalactosyldiacylglycerol facilitates the
synthesis of Pchlide and the formation of the Pchlide-LPOR-NADPH complex in
etioplasts, but the importance of DGDG in etioplasts is still unknown. To
determine the role of DGDG in etioplast development and functions, we
characterized a knockout mutant (dgd1) of Arabidopsis (Arabidopsis thaliana)
DGD1, which encodes the major isoform of DGDG synthase, in the etioplast
development stage. In etiolated dgd1 seedlings, DGDG content decreased to 20% of
the wild-type level, the lattice structure of PLBs was disordered, and the
development of prothylakoids was impaired. In addition, membrane-associated
processes of Pchlide biosynthesis, formation of the Pchlide-LPOR-NADPH complex,
and dissociation of the complex after the photoconversion of Pchlide to
chlorophyllide were impaired in dgd1, although the photoconversion reaction by
LPOR was not affected by the DGDG deficiency. Total carotenoid content also
decreased in etiolated dgd1 seedlings, but the carotenoid composition was
unchanged. Our data demonstrate a deep involvement of DGDG in the formation of
the internal membrane structures in etioplasts as well as in membrane-associated
processes of pigment biosynthesis and pigment-protein complex organization.
PMID- 29946020
TI - Gene expression distribution deconvolution in single-cell RNA sequencing.
AB - Single-cell RNA sequencing (scRNA-seq) enables the quantification of each gene's
expression distribution across cells, thus allowing the assessment of the
dispersion, nonzero fraction, and other aspects of its distribution beyond the
mean. These statistical characterizations of the gene expression distribution are
critical for understanding expression variation and for selecting marker genes
for population heterogeneity. However, scRNA-seq data are noisy, with each cell
typically sequenced at low coverage, thus making it difficult to infer properties
of the gene expression distribution from raw counts. Based on a reexamination of
nine public datasets, we propose a simple technical noise model for scRNA-seq
data with unique molecular identifiers (UMI). We develop deconvolution of single
cell expression distribution (DESCEND), a method that deconvolves the true cross
cell gene expression distribution from observed scRNA-seq counts, leading to
improved estimates of properties of the distribution such as dispersion and
nonzero fraction. DESCEND can adjust for cell-level covariates such as cell size,
cell cycle, and batch effects. DESCEND's noise model and estimation accuracy are
further evaluated through comparisons to RNA FISH data, through data splitting
and simulations and through its effectiveness in removing known batch effects. We
demonstrate how DESCEND can clarify and improve downstream analyses such as
finding differentially expressed genes, identifying cell types, and selecting
differentiation markers.
PMID- 29946021
TI - Rayleigh-Taylor instabilities in high-energy density settings on the National
Ignition Facility.
AB - The Rayleigh-Taylor (RT) instability occurs at an interface between two fluids of
differing density during an acceleration. These instabilities can occur in very
diverse settings, from inertial confinement fusion (ICF) implosions over spatial
scales of [Formula: see text] cm (10-1,000 MUm) to supernova explosions at
spatial scales of [Formula: see text] cm and larger. We describe experiments and
techniques for reducing ("stabilizing") RT growth in high-energy density (HED)
settings on the National Ignition Facility (NIF) at Lawrence Livermore National
Laboratory. Three unique regimes of stabilization are described: (i) at an
ablation front, (ii) behind a radiative shock, and (iii) due to material
strength. For comparison, we also show results from nonstabilized "classical" RT
instability evolution in HED regimes on the NIF. Examples from experiments on the
NIF in each regime are given. These phenomena also occur in several astrophysical
scenarios and planetary science [Drake R (2005) Plasma Phys Controlled Fusion
47:B419-B440; Dahl TW, Stevenson DJ (2010) Earth Planet Sci Lett 295:177-186].
PMID- 29946022
TI - Single-cell mutagenic responses and cell death revealed in real time.
PMID- 29946023
TI - Learning atoms for materials discovery.
AB - Exciting advances have been made in artificial intelligence (AI) during recent
decades. Among them, applications of machine learning (ML) and deep learning
techniques brought human-competitive performances in various tasks of fields,
including image recognition, speech recognition, and natural language
understanding. Even in Go, the ancient game of profound complexity, the AI player
has already beat human world champions convincingly with and without learning
from the human. In this work, we show that our unsupervised machines (Atom2Vec)
can learn the basic properties of atoms by themselves from the extensive database
of known compounds and materials. These learned properties are represented in
terms of high-dimensional vectors, and clustering of atoms in vector space
classifies them into meaningful groups consistent with human knowledge. We use
the atom vectors as basic input units for neural networks and other ML models
designed and trained to predict materials properties, which demonstrate
significant accuracy.
PMID- 29946024
TI - Sex-chromosome dosage effects on gene expression in humans.
AB - A fundamental question in the biology of sex differences has eluded direct study
in humans: How does sex-chromosome dosage (SCD) shape genome function? To address
this, we developed a systematic map of SCD effects on gene function by analyzing
genome-wide expression data in humans with diverse sex-chromosome aneuploidies
(XO, XXX, XXY, XYY, and XXYY). For sex chromosomes, we demonstrate a pattern of
obligate dosage sensitivity among evolutionarily preserved X-Y homologs and
update prevailing theoretical models for SCD compensation by detecting X-linked
genes that increase expression with decreasing X- and/or Y-chromosome dosage. We
further show that SCD-sensitive sex-chromosome genes regulate specific
coexpression networks of SCD-sensitive autosomal genes with critical cellular
functions and a demonstrable potential to mediate previously documented SCD
effects on disease. These gene coexpression results converge with analysis of
transcription factor binding site enrichment and measures of gene expression in
murine knockout models to spotlight the dosage-sensitive X-linked transcription
factor ZFX as a key mediator of SCD effects on wider genome expression. Our
findings characterize the effects of SCD broadly across the genome, with
potential implications for human phenotypic variation.
PMID- 29946026
TI - Whole-genome data reveal the complex history of a diverse ecological community.
AB - How widespread ecological communities assemble remains a key question in ecology.
Trophic interactions between widespread species may reflect a shared population
history or ecological fitting of local pools of species with very different
population histories. Which scenario applies is central to the stability of
trophic associations and the potential for coevolution between species. Here we
show how alternative community assembly hypotheses can be discriminated using
whole-genome data for component species and provide a likelihood framework that
overcomes current limitations in formal comparison of multispecies histories. We
illustrate our approach by inferring the assembly history of a Western Palearctic
community of insect herbivores and parasitoid natural enemies, trophic groups
that together comprise 50% of terrestrial species. We reject models of
codispersal from a shared origin and of delayed enemy pursuit of their herbivore
hosts, arguing against herbivore attainment of "enemy-free space." The community
wide distribution of species expansion times is also incompatible with a random,
neutral model of assembly. Instead, we reveal a complex assembly history of
single- and multispecies range expansions through the Pleistocene from different
directions and over a range of timescales. Our results suggest substantial
turnover in species associations and argue against tight coevolution in this
system. The approach we illustrate is widely applicable to natural communities of
nonmodel species and makes it possible to reveal the historical backdrop against
which natural selection acts.
PMID- 29946025
TI - Evolutionary genomic dynamics of Peruvians before, during, and after the Inca
Empire.
AB - Native Americans from the Amazon, Andes, and coastal geographic regions of South
America have a rich cultural heritage but are genetically understudied, therefore
leading to gaps in our knowledge of their genomic architecture and demographic
history. In this study, we sequence 150 genomes to high coverage combined with an
additional 130 genotype array samples from Native American and mestizo
populations in Peru. The majority of our samples possess greater than 90% Native
American ancestry, which makes this the most extensive Native American sequencing
project to date. Demographic modeling reveals that the peopling of Peru began
~12,000 y ago, consistent with the hypothesis of the rapid peopling of the
Americas and Peruvian archeological data. We find that the Native American
populations possess distinct ancestral divisions, whereas the mestizo groups were
admixtures of multiple Native American communities that occurred before and
during the Inca Empire and Spanish rule. In addition, the mestizo communities
also show Spanish introgression largely following Peruvian Independence, nearly
300 y after Spain conquered Peru. Further, we estimate migration events between
Peruvian populations from all three geographic regions with the majority of
between-region migration moving from the high Andes to the low-altitude Amazon
and coast. As such, we present a detailed model of the evolutionary dynamics
which impacted the genomes of modern-day Peruvians and a Native American ancestry
dataset that will serve as a beneficial resource to addressing the
underrepresentation of Native American ancestry in sequencing studies.
PMID- 29946027
TI - Structural basis for recognition of human 7SK long noncoding RNA by the La
related protein Larp7.
AB - The La and the La-related protein (LARP) superfamily is a diverse class of RNA
binding proteins involved in RNA processing, folding, and function. Larp7 binds
to the abundant long noncoding 7SK RNA and is required for 7SK ribonucleoprotein
(RNP) assembly and function. The 7SK RNP sequesters a pool of the positive
transcription elongation factor b (P-TEFb) in an inactive state; on release, P
TEFb phosphorylates RNA Polymerase II to stimulate transcription elongation.
Despite its essential role in transcription, limited structural information is
available for the 7SK RNP, particularly for protein-RNA interactions. Larp7
contains an N-terminal La module that binds UUU-3'OH and a C-terminal atypical
RNA recognition motif (xRRM) required for specific binding to 7SK and P-TEFb
assembly. Deletion of the xRRM is linked to gastric cancer in humans. We report
the 2.2-A X-ray crystal structure of the human La-related protein group 7
(hLarp7) xRRM bound to the 7SK stem-loop 4, revealing a unique binding interface.
Contributions of observed interactions to binding affinity were investigated by
mutagenesis and isothermal titration calorimetry. NMR 13C spin relaxation data
and comparison of free xRRM, RNA, and xRRM-RNA structures show that the xRRM is
preordered to bind a flexible loop 4. Combining structures of the hLarp7 La
module and the xRRM-7SK complex presented here, we propose a structural model for
Larp7 binding to the 7SK 3' end and mechanism for 7SK RNP assembly. This work
provides insight into how this domain contributes to 7SK recognition and assembly
of the core 7SK RNP.
PMID- 29946028
TI - Amyloid clearance defect in ApoE4 astrocytes is reversed by epigenetic correction
of endosomal pH.
AB - Endosomes have emerged as a central hub and pathogenic driver of Alzheimer's
disease (AD). The earliest brain cytopathology in neurodegeneration, occurring
decades before amyloid plaques and cognitive decline, is an expansion in the size
and number of endosomal compartments. The strongest genetic risk factor for
sporadic AD is the epsilon4 allele of Apolipoprotein E (ApoE4). Previous studies
have shown that ApoE4 potentiates presymptomatic endosomal dysfunction and
defective endocytic clearance of amyloid beta (Abeta), although how these two
pathways are linked at a cellular and mechanistic level has been unclear. Here,
we show that aberrant endosomal acidification in ApoE4 astrocytes traps the low
density lipoprotein receptor-related protein (LRP1) within intracellular
compartments, leading to loss of surface expression and Abeta clearance.
Pathological endosome acidification is caused by epsilon4 risk allele-selective
down-regulation of the Na+/H+ exchanger isoform NHE6, which functions as a
critical leak pathway for endosomal protons. In vivo, the NHE6 knockout (NHE6KO)
mouse model showed elevated Abeta in the brain, consistent with a causal effect.
Increased nuclear translocation of histone deacetylase 4 (HDAC4) in ApoE4
astrocytes, compared with the nonpathogenic ApoE3 allele, suggested a mechanistic
basis for transcriptional down-regulation of NHE6. HDAC inhibitors that restored
NHE6 expression normalized ApoE4-specific defects in endosomal pH, LRP1
trafficking, and amyloid clearance. Thus, NHE6 is a downstream effector of ApoE4
and emerges as a promising therapeutic target in AD. These observations have
prognostic implications for patients who have Christianson syndrome with loss of
function mutations in NHE6 and exhibit prominent glial pathology and progressive
hallmarks of neurodegeneration.
PMID- 29946029
TI - Gentamicin induces LAMB3 nonsense mutation readthrough and restores functional
laminin 332 in junctional epidermolysis bullosa.
AB - Herlitz junctional epidermolysis bullosa (H-JEB) is an incurable, devastating,
and mostly fatal inherited skin disease for which there is only supportive care.
H-JEB is caused by loss-of-function mutations in LAMA3, LAMB3, or LAMC2, leading
to complete loss of laminin 332, the major component of anchoring filaments,
which mediate epidermal-dermal adherence. LAMB3 (laminin beta3) mutations account
for 80% of patients with H-JEB, and ~95% of H-JEB-associated LAMB3 mutations are
nonsense mutations leading to premature termination codons (PTCs). In this study,
we evaluated the ability of gentamicin to induce PTC readthrough in H-JEB laminin
beta3-null keratinocytes transfected with expression vectors encoding eight
different LAMB3 nonsense mutations. We found that gentamicin induced PTC
readthrough in all eight nonsense mutations tested. We next used lentiviral
vectors to generate stably transduced H-JEB cells with the R635X and C290X
nonsense mutations. Incubation of these cell lines with various concentrations of
gentamicin resulted in the synthesis and secretion of full-length laminin beta3
in a dose-dependent and sustained manner. Importantly, the gentamicin-induced
laminin beta3 led to the restoration of laminin 332 assembly, secretion, and
deposition within the dermal/epidermal junction, as well as proper polarization
of alpha6beta4 integrin in basal keratinocytes, as assessed by immunoblot
analysis, immunofluorescent microscopy, and an in vitro 3D skin equivalent model.
Finally, newly restored laminin 332 corrected the abnormal cellular phenotype of
H-JEB cells by reversing abnormal cell morphology, poor growth potential, poor
cell-substratum adhesion, and hypermotility. Therefore, gentamicin may offer a
therapy for H-JEB and other inherited skin diseases caused by PTC mutations.
PMID- 29946030
TI - Molecular model of human tropoelastin and implications of associated mutations.
AB - Protein folding poses unique challenges for large, disordered proteins due to the
low resolution of structural data accessible in experiment and on the basis of
short time scales and limited sampling attainable in computation. Such molecules
are uniquely suited to accelerated-sampling molecular dynamics algorithms due to
a flat-energy landscape. We apply these methods to report here the folded
structure in water from a fully extended chain of tropoelastin, a 698-amino acid
molecular precursor to elastic fibers that confer elasticity and recoil to
tissues, finding good agreement with experimental data. We then study a series of
artificial and disease-related mutations, yielding molecular mechanisms to
explain structural differences and variation in hierarchical assembly observed in
experiment. The present model builds a framework for studying assembly and
disease and yields critical insight into molecular mechanisms behind these
processes. These results suggest that proteins with disordered regions are
suitable candidates for characterization by this approach.
PMID- 29946032
TI - Dynamically reinforced heterogeneous grain structure prolongs ductility in a
medium-entropy alloy with gigapascal yield strength.
AB - Ductility, i.e., uniform strain achievable in uniaxial tension, diminishes for
materials with very high yield strength. Even for the CrCoNi medium-entropy alloy
(MEA), which has a simple face-centered cubic (FCC) structure that would bode
well for high ductility, the fine grains processed to achieve gigapascal strength
exhaust the strain hardening ability such that, after yielding, the uniform
tensile strain is as low as ~2%. Here we purposely deploy, in this MEA, a three
level heterogeneous grain structure (HGS) with grain sizes spanning the nanometer
to micrometer range, imparting a high yield strength well in excess of 1 GPa.
This heterogeneity results from this alloy's low stacking fault energy, which
facilitates corner twins in recrystallization and stores deformation twins and
stacking faults during tensile straining. After yielding, the elastoplastic
transition through load transfer and strain partitioning among grains of
different sizes leads to an upturn of the strain hardening rate, and, upon
further tensile straining at room temperature, corner twins evolve into
nanograins. This dynamically reinforced HGS leads to a sustainable strain
hardening rate, a record-wide hysteresis loop in load-unload-reload stress-strain
curve and hence high back stresses, and, consequently, a uniform tensile strain
of 22%. As such, this HGS achieves, in a single-phase FCC alloy, a strength
ductility combination that would normally require heterogeneous microstructures
such as in dual-phase steels.
PMID- 29946031
TI - Arthropod EVs mediate dengue virus transmission through interaction with a
tetraspanin domain containing glycoprotein Tsp29Fb.
AB - Dengue virus (DENV) is a mosquito-borne flavivirus that causes dengue fever in
humans, worldwide. Using in vitro cell lines derived from Aedes albopictus and
Aedes aegypti, the primary vectors of DENV, we report that DENV2/DENV3-infected
cells secrete extracellular vesicles (EVs), including exosomes, containing
infectious viral RNA and proteins. A full-length DENV2 genome, detected in
arthropod EVs, was infectious to naive mosquito and mammalian cells, including
human-skin keratinocytes and blood endothelial cells. Cryo-electron microscopy
showed mosquito EVs with a size range from 30 to 250 nm. Treatments with RNase A,
Triton X-100, and 4G2 antibody-bead binding assays showed that infectious DENV2
RNA and proteins are contained inside EVs. Viral plaque formation and dilution
assays also showed securely contained infectious viral RNA and proteins in EVs
are transmitted to human cells. Up-regulated HSP70 upon DENV2 infection showed no
role in viral replication and transmission through EVs. In addition, qRT-PCR and
immunoblotting results revealed that DENV2 up-regulates expression of a mosquito
tetraspanin-domain-containing glycoprotein, designated as Tsp29Fb, in A. aegypti
mosquitoes, cells, and EVs. RNAi-mediated silencing and antibody blocking of
Tsp29Fb resulted in reduced DENV2 loads in both mosquito cells and EVs.
Immunoprecipitation showed Tsp29Fb to directly interact with DENV2 E-protein.
Furthermore, treatment with GW4869 (exosome-release inhibitor) affected viral
burden, direct interaction of Tsp29Fb with E-protein and EV-mediated transmission
of viral RNA and proteins to naive human cells. In summary, we report a very
important finding on EV-mediated transmission of DENV2 from arthropod to
mammalian cells through interactions with an arthropod EVs-enriched marker
Tsp29Fb.
PMID- 29946034
TI - Action potential counting at giant mossy fiber terminals gates information
transfer in the hippocampus.
AB - Neuronal communication relies on action potential discharge, with the frequency
and the temporal precision of action potentials encoding information. Hippocampal
mossy fibers have long been recognized as conditional detonators owing to
prominent short-term facilitation of glutamate release displayed during granule
cell burst firing. However, the spiking patterns required to trigger action
potential firing in CA3 pyramidal neurons remain poorly understood. Here, we show
that glutamate release from mossy fiber terminals triggers action potential
firing of the target CA3 pyramidal neurons independently of the average granule
cell burst frequency, a phenomenon we term action potential counting. We find
that action potential counting in mossy fibers gates glutamate release over a
broad physiological range of frequencies and action potential numbers. Using
rapid Ca2+ imaging we also show that the magnitude of evoked Ca2+ influx stays
constant during action potential trains and that accumulated residual Ca2+ is
gradually extruded on a time scale of several hundred milliseconds. Using
experimentally constrained 3D model of presynaptic Ca2+ influx, buffering, and
diffusion, and a Monte Carlo model of Ca2+-activated vesicle fusion, we argue
that action potential counting at mossy fiber boutons can be explained by a
unique interplay between Ca2+ dynamics and buffering at release sites. This is
largely determined by the differential contribution of major endogenous Ca2+
buffers calbindin-D28K and calmodulin and by the loose coupling between
presynaptic voltage-gated Ca2+ channels and release sensors and the relatively
slow Ca2+ extrusion rate. Taken together, our results identify a previously
unexplored information-coding mechanism in the brain.
PMID- 29946033
TI - Catalytic iron-carbene intermediate revealed in a cytochrome c carbene
transferase.
AB - Recently, heme proteins have been discovered and engineered by directed evolution
to catalyze chemical transformations that are biochemically unprecedented. Many
of these nonnatural enzyme-catalyzed reactions are assumed to proceed through a
catalytic iron porphyrin carbene (IPC) intermediate, although this intermediate
has never been observed in a protein. Using crystallographic, spectroscopic, and
computational methods, we have captured and studied a catalytic IPC intermediate
in the active site of an enzyme derived from thermostable Rhodothermus marinus
(Rma) cytochrome c High-resolution crystal structures and computational methods
reveal how directed evolution created an active site for carbene transfer in an
electron transfer protein and how the laboratory-evolved enzyme achieves perfect
carbene transfer stereoselectivity by holding the catalytic IPC in a single
orientation. We also discovered that the IPC in Rma cytochrome c has a singlet
ground electronic state and that the protein environment uses geometrical
constraints and noncovalent interactions to influence different IPC electronic
states. This information helps us to understand the impressive reactivity and
selectivity of carbene transfer enzymes and offers insights that will guide and
inspire future engineering efforts.
PMID- 29946035
TI - Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven
by oxygen-dependent growth inhibition.
AB - Sickle cell trait (AS) confers partial protection against lethal Plasmodium
falciparum malaria. Multiple mechanisms for this have been proposed, with a
recent focus on aberrant cytoadherence of parasite-infected red blood cells
(RBCs). Here we investigate the mechanistic basis of AS protection through
detailed temporal mapping. We find that parasites in AS RBCs maintained at low
oxygen concentrations stall at a specific stage in the middle of intracellular
growth before DNA replication. We demonstrate that polymerization of sickle
hemoglobin (HbS) is responsible for this growth arrest of intraerythrocytic P.
falciparum parasites, with normal hemoglobin digestion and growth restored in the
presence of carbon monoxide, a gaseous antisickling agent. Modeling of growth
inhibition and sequestration revealed that HbS polymerization-induced growth
inhibition following cytoadherence is the critical driver of the reduced parasite
densities observed in malaria infections of individuals with AS. We conclude that
the protective effect of AS derives largely from effective sequestration of
infected RBCs into the hypoxic microcirculation.
PMID- 29946036
TI - Drosophila model of myosin myopathy rescued by overexpression of a TRIM-protein
family member.
AB - Myosin is a molecular motor indispensable for body movement and heart
contractility. Apart from pure cardiomyopathy, mutations in MYH7 encoding
slow/beta-cardiac myosin heavy chain also cause skeletal muscle disease with or
without cardiac involvement. Mutations within the alpha-helical rod domain of
MYH7 are mainly associated with Laing distal myopathy. To investigate the
mechanisms underlying the pathology of the recurrent causative MYH7 mutation
(K1729del), we have developed a Drosophila melanogaster model of Laing distal
myopathy by genomic engineering of the Drosophila Mhc locus. Homozygous
MhcK1728del animals die during larval/pupal stages, and both homozygous and
heterozygous larvae display reduced muscle function. Flies expressing only
MhcK1728del in indirect flight and jump muscles, and heterozygous MhcK1728del
animals, were flightless, with reduced movement and decreased lifespan.
Sarcomeres of MhcK1728del mutant indirect flight muscles and larval body wall
muscles were disrupted with clearly disorganized muscle filaments. Homozygous
MhcK1728del larvae also demonstrated structural and functional impairments in
heart muscle, which were not observed in heterozygous animals, indicating a dose
dependent effect of the mutated allele. The impaired jump and flight ability and
the myopathy of indirect flight and leg muscles associated with MhcK1728del were
fully suppressed by expression of Abba/Thin, an E3-ligase that is essential for
maintaining sarcomere integrity. This model of Laing distal myopathy in
Drosophila recapitulates certain morphological phenotypic features seen in Laing
distal myopathy patients with the recurrent K1729del mutation. Our observations
that Abba/Thin modulates these phenotypes suggest that manipulation of Abba/Thin
activity levels may be beneficial in Laing distal myopathy.
PMID- 29946037
TI - Kinetically guided radical-based synthesis of C(sp3)-C(sp3) linkages on DNA.
AB - DNA-encoded libraries (DEL)-based discovery platforms have recently been widely
adopted in the pharmaceutical industry, mainly due to their powerful diversity
and incredible number of molecules. In the two decades since their disclosure,
great strides have been made to expand the toolbox of reaction modes that are
compatible with the idiosyncratic aqueous, dilute, and DNA-sensitive parameters
of this system. However, construction of highly important C(sp3)-C(sp3) linkages
on DNA through cross-coupling remains unexplored. In this article, we describe a
systematic approach to translating standard organic reactions to a DEL setting
through the tactical combination of kinetic analysis and empirical screening with
information captured from data mining. To exemplify this model, implementation of
the Giese addition to forge high value C-C bonds on DNA was studied, which
represents a radical-based synthesis in DEL.
PMID- 29946038
TI - Galectin-3 in M2 Macrophages Plays a Protective Role in Resolution of
Neuropathology in Brain Parasitic Infection by Regulating Neutrophil Turnover.
AB - Macrophages/microglia with M2-activation phenotype are thought to play important
anti-inflammatory and tissue reparative functions in the brain, yet the molecular
bases of their functions in the CNS remain to be clearly defined. In a
preclinical model of neurocysticercosis using brain infection with a parasite
Mesocestoides corti, we previously reported the presence of large numbers of M2
cells in the CNS. In this study using female mice, we report that M2 macrophages
in the parasite-infected brain display abundant galectin-3 expression. Disease
severity was increased in Galectin-3-/- mice correlating with increased
neurological defects, augmented cell death and, importantly, massive accumulation
of neutrophils and M2 macrophages in the CNS of these mice. Because neutrophil
clearance by efferocytosis is an important function of M2 macrophages, we
investigated a possible role of galectin-3 in this process. Indeed, galectin-3
deficient M2 macrophages exhibited a defect in efferocytic clearance of
neutrophils in vitro Furthermore, adoptive transfer of M2 macrophages from
galectin-3-sufficient WT mice reduced neutrophilia in the CNS and ameliorated
disease severity in parasite-infected Galectin-3-/- mice. Together, these results
demonstrate, for the first time, a novel role of galectin-3 in M2 macrophage
function in neutrophil turnover and resolution of inflammatory pathology in the
CNS. This likely will have implications in neurocysticercosis and
neuroinflammatory diseases.SIGNIFICANCE STATEMENT Macrophages/microglia with M1
activation phenotype are thought to promote CNS pathology, whereas M2-anti
inflammatory phenotype promote CNS repair. However, the mechanisms regulating M2
cell-protective functions in the CNS microenvironment are undefined. The current
study reports that helminth infection of the brain induces an increased
expression of galectin-3 in M2 macrophages accumulated in the CNS. Using multiple
experimental models in vivo and in vitro, they show that galectin-3 in M2
macrophages functions to clear neutrophils accumulated in the CNS. Importantly,
galectin-3 in M2 macrophages plays a central role in the containment of
neuropathology and disease severity. These results provide a direct mechanistic
evidence of the protective function of M2 macrophages in the CNS.
PMID- 29946039
TI - Endogenous Protection from Ischemic Brain Injury by Preconditioned Monocytes.
AB - Exposure to low-dose lipopolysaccharide (LPS) before cerebral ischemia is
neuroprotective in stroke models, a phenomenon termed preconditioning (PC).
Although it is well established that LPS-PC induces central and peripheral immune
responses, the cellular mechanisms modulating ischemic injury remain unclear.
Here, we investigated the role of immune cells in the brain protection afforded
by PC and tested whether monocytes may be reprogrammed by ex vivo LPS exposure,
thus modulating inflammatory injury after cerebral ischemia in male mice. We
found that systemic injection of low-dose LPS induces a Ly6Chi monocyte response
that protects the brain after transient middle cerebral artery occlusion (MCAO)
in mice. Remarkably, adoptive transfer of monocytes isolated from preconditioned
mice into naive mice 7 h after transient MCAO reduced brain injury. Gene
expression and functional studies showed that IL-10, inducible nitric oxide
synthase, and CCR2 in monocytes are essential for neuroprotection. This
protective activity was elicited even if mouse or human monocytes were exposed ex
vivo to LPS and then injected into male mice after stroke. Cell-tracking studies
showed that protective monocytes are mobilized from the spleen and reach the
brain and meninges, where they suppress postischemic inflammation and neutrophil
influx into the brain parenchyma. Our findings unveil a previously unrecognized
subpopulation of splenic monocytes capable of protecting the brain with an
extended therapeutic window and provide the rationale for cell therapies based on
the delivery of autologous or allogeneic protective monocytes in patients after
ischemic stroke.SIGNIFICANCE STATEMENT Inflammation is a key component of the
pathophysiology of the brain in stroke, a leading cause of death and disability
with limited therapeutic options. Here, we investigate endogenous mechanisms of
protection against cerebral ischemia. Using lipopolysaccharide (LPS)
preconditioning (PC) as an approach to induce ischemic tolerance in mice, we
found generation of neuroprotective monocytes within the spleen, from which they
traffic to the brain and meninges, suppressing postischemic inflammation.
Importantly, systemic LPS-PC can be mimicked by adoptive transfer of in vitro
preconditioned mouse or human monocytes at translational relevant time points
after stroke. This model of neuroprotection may facilitate clinical efforts to
increase the efficacy of BM mononuclear cell treatments in acute neurological
diseases such as cerebral ischemia.
PMID- 29946041
TI - Pennies for Our Thoughts.
PMID- 29946040
TI - Multifaceted but Invisible: Perceptions of the Value of a Pediatric Cognitive
Specialty.
AB - BACKGROUND: Systems for standardizing physician payment have been shown to
undervalue cognitive clinical encounters. Because health care reform emphasizes
value-based approaches, we need an understanding of the way pediatric cognitive
specialties are used to contribute to the provision of high-value care. We sought
to investigate how clinical and administrative stakeholders perceive the value of
pediatric infectious disease (PID) specialists. METHODS: We conducted qualitative
interviews with a purposive sample of physicians and administrators from 5
hospitals across the United States in which children are cared for. All
interviews were transcribed and systematically analyzed for common themes.
RESULTS: We interviewed 97 stakeholders. Analysis revealed the following 3
domains of value: clinical, organizational, and communicative. Clinically, PID
specialists were perceived to be highly valuable in treating patients with
unusual infections that respond poorly to therapy, in optimizing the use of
antimicrobial agents and in serving as outpatient homes for complex patients.
Respondents perceived that PID specialists facilitate communication with patients
and their families, the health care team and the media. PID specialists were
perceived to generate value by participating in systemwide activities, including
antimicrobial stewardship and infection prevention. Despite this, much of the
valuable work PID specialists perform is difficult to measure causing some
administrative stakeholders to question how many PID specialists are necessary to
achieve high-quality care. CONCLUSIONS: With our findings, we suggest that
pediatric cognitive specialties contribute value in multiple ways to the health
care delivery system. Many of these domains are difficult to capture by using
current metrics, which may lead administrators to overlook valuable work and to
under-allocate resources.
PMID- 29946043
TI - Doctors call for cap on GP workload.
PMID- 29946042
TI - The multifaceted allosteric regulation of Aurora kinase A.
AB - The protein kinase Aurora A (AurA) is essential for the formation of bipolar
mitotic spindles in all eukaryotic organisms. During spindle assembly, AurA is
activated through two different pathways operating at centrosomes and on spindle
microtubules. Recent studies have revealed that these pathways operate quite
differently at the molecular level, activating AurA through multifaceted changes
to the structure and dynamics of the kinase domain. These advances provide an
intimate atomic-level view of the finely tuned regulatory control operating in
protein kinases, revealing mechanisms of allosteric cooperativity that provide
graded levels of regulatory control, and a previously unanticipated mechanism for
kinase activation by phosphorylation on the activation loop. Here, I review these
advances in our understanding of AurA function, and discuss their implications
for the use of allosteric small molecule inhibitors to address recently
discovered roles of AurA in neuroblastoma, prostate cancer and melanoma.
PMID- 29946044
TI - Introduction of Large Sequence Inserts by CRISPR-Cas9 To Create Pathogenicity
Mutants in the Multinucleate Filamentous Pathogen Sclerotinia sclerotiorum.
AB - The necrotrophic fungal plant pathogen Sclerotinia sclerotiorum is responsible
for substantial global crop losses annually resulting in localized food
insecurity and loss of livelihood. Understanding the basis of this broad-host
range and aggressive pathogenicity is hampered by the quantitative nature of both
host resistance and pathogen virulence. To improve this understanding, methods
for efficient functional gene characterization that build upon the existing
complete S. sclerotiorum genome sequence are needed. Here, we report on the
development of a clustered regularly interspaced short palindromic repeat
(CRISPR)-CRISPR-associated protein 9 (CRISPR-Cas9)-mediated strategy for creating
gene disruption mutants and the application of this technique for exploring roles
of known and hypothesized virulence factors. A key finding of this research is
that transformation with a circular plasmid encoding Cas9, target single guide
RNA (sgRNA), and a selectable marker resulted in a high frequency of targeted,
insertional gene mutation. We observed that 100% of the mutants integrated large
rearranged segments of the transforming plasmid at the target site facilitated by
the nonhomologous end joining (NHEJ) repair pathway. This result was confirmed in
multiple target sites within the same gene in three independent wild-type
isolates of S. sclerotiorum and in a second independent gene. Targeting the
previously characterized Ssoah1 gene allowed us to confirm the loss-of-function
nature of the CRISPR-Cas9-mediated mutants and explore new aspects of the mutant
phenotype. Applying this technology to create mutations in a second previously
uncharacterized gene allowed us to determine the requirement for melanin
accumulation in infection structure development and function.IMPORTANCE Fungi
that cause plant diseases by rotting or blighting host tissue with limited
specificity remain among the most difficult to control. This is largely due to
the quantitative nature of host resistance and a limited understanding of fungal
pathogenicity. A mechanistic understanding of pathogenicity requires the ability
to manipulate candidate virulence genes to test hypotheses regarding their roles
in disease development. Sclerotinia sclerotiorum is among the most notorious of
these so-called broad-host-range necrotrophic plant pathogens. The work described
here provides a new method for rapidly constructing gene disruption vectors to
create gene mutations with high efficiency compared with existing methods.
Applying this method to characterize gene functions in S. sclerotiorum, we
confirm the requirement for oxalic acid production as a virulence factor in
multiple isolates of the fungus and demonstrate that melanin accumulation is not
required for infection. Using this approach, the pace of functional gene
characterization and the understanding of pathogenicity and related disease
resistance will increase.
PMID- 29946045
TI - Identification of Host Factors Involved in Human Cytomegalovirus Replication,
Assembly, and Egress Using a Two-Step Small Interfering RNA Screen.
AB - As obligate intracellular parasites, viruses are completely dependent on host
factors for replication. Assembly and egress of complex virus particles, such as
human cytomegalovirus (HCMV), are likely to require many host factors. Despite
this, relatively few have been identified and characterized. This study describes
a novel high-throughput, two-step small interfering RNA (siRNA) screen, which
independently measures virus replication and virus production. By combining data
from replication and virus production, multiple candidate genes were identified
in which knockdown resulted in substantial loss of virus production with limited
effect on primary replication, suggesting roles in later stages such as virus
assembly and egress. Knockdown of the top candidates, ERC1, RAB4B, COPA, and
COPB2, caused profound loss of virus production. Despite COPA and COPB2 being
reported to function in the same complex, knockdown of these genes produced
distinct phenotypes. Furthermore, knockdown of COPA caused increased expression
of viral late genes despite substantial inhibition of viral DNA replication. This
suggests that efficient viral genome replication is not required for late gene
expression. Finally, we show that RAB4B relocates to the viral assembly
compartment following infection with HCMV and knockdown of RAB4B reduces the
release of intact virion particles, suggesting that it plays a role in virion
assembly and egress. This study demonstrates a powerful high-throughput screen
for identification of host-virus interactions, identifies multiple host genes
associated with HCMV assembly and egress, and uncovers potentially independent
functions for coatomer components COPA and COPB2 during infection.IMPORTANCE
Human cytomegalovirus infection is a significant cause of disease in
immunocompromised populations, individuals with heart disease, and recipients of
solid organ and bone marrow transplants. HCMV is also the leading cause of
infectious congenital birth defects. The majority of antivirals in clinical use
target components of the virus to specifically inhibit replication. However, a
major drawback of this approach is the emergence of resistance. An alternative
approach is to target host factors that the virus requires for successful
infection. In this study, multiple host factors were identified that were found
to be essential for the production of newly infectious human cytomegalovirus.
Identifying which host genes are necessary for virus replication extends our
understanding of how viruses replicate and how cells function and provides
potential targets for novel antivirals.
PMID- 29946047
TI - A Novel Method of Serum Resistance by Escherichia coli That Causes Urosepsis.
AB - Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract
infection, which in some patients can develop into life-threatening urosepsis.
Serum resistance is a key virulence trait of strains that cause urosepsis.
Recently, we identified a novel method of serum resistance in patients with
Pseudomonas aeruginosa lung infections, where patients possessed antibodies that
inhibited complement-mediated killing (instead of protecting against infection).
These inhibitory antibodies were of the IgG2 subtype, specific to the O-antigen
component of lipopolysaccharide (LPS) and coated the bacterial surface,
preventing bacterial lysis by complement. As this mechanism could apply to any
Gram-negative bacterial infection, we hypothesized that inhibitory antibodies may
represent an uncharacterized mechanism of serum resistance in UPEC. To test this,
45 urosepsis patients with paired blood culture UPEC isolates were screened for
serum titers of IgG2 specific for their cognate strain's LPS. Eleven patients had
sufficiently high titers of the antibody to inhibit serum-mediated killing of
UPEC isolates by pooled healthy control sera. Depletion of IgG or removal of O
antigen restored sensitivity of the isolates to the cognate patient serum.
Importantly, the isolates from these 11 patients were more sensitive to killing
by serum than isolates from patients with no inhibitory antibodies. This suggests
the presence of inhibitory antibodies may have allowed these strains to infect
the bloodstream. The high prevalence of patients with inhibitory antibodies (24%)
suggests that this phenomenon is an important mechanism of UPEC serum resistance.
LPS-specific inhibitory antibodies have now been identified against three Gram
negative pathogens that cause disparate diseases.IMPORTANCE Despite improvements
in the early detection and management of sepsis, morbidity and mortality are
still high. Infections of the urinary tract are one of the most frequent sources
of sepsis with Escherichia coli the main causative agent. Serum resistance is
vital for bacteria to infect the bloodstream. Here we report a novel method of
serum resistance found in patients with UPEC-mediated sepsis. Antibodies in sera
usually protect against infection, but here we found that 24% of patients
expressed "inhibitory antibodies" capable of preventing serum-mediated killing of
their infecting isolate. Our data suggest that these antibodies would allow
otherwise serum-sensitive UPEC strains to cause sepsis. The high prevalence of
patients with inhibitory antibodies in this cohort suggests that this is a
widespread mechanism of resistance to complement-mediated killing in urosepsis
patients, invoking the potential for the application of new methods to prevent
and treat sepsis.
PMID- 29946046
TI - Trichomonas vaginalis Macrophage Migration Inhibitory Factor Mediates Parasite
Survival during Nutrient Stress.
AB - Trichomonas vaginalis is responsible for the most prevalent non-viral sexually
transmitted disease worldwide, and yet the mechanisms used by this parasite to
establish and maintain infection are poorly understood. We previously identified
a T. vaginalis homologue (TvMIF) of a human cytokine, human macrophage migration
inhibitory factor (huMIF). TvMIF mimics huMIF's role in increasing cell growth
and inhibiting apoptosis in human host cells. To interrogate a role of TvMIF in
parasite survival during infection, we asked whether overexpression of TvMIF
(TvMIF-OE) confers an advantage to the parasite under nutrient stress conditions
by comparing the survival of TvMIF-OE parasites to that of empty vector (EV)
parasites. We found that under conditions of serum starvation, overexpression of
TvMIF resulted in increased parasite survival. Serum-starved parasites secrete
2.5-fold more intrinsic TvMIF than unstarved parasites, stimulating autocrine and
paracrine signaling. Similarly, we observed that addition of recombinant TvMIF
increased the survival of the parasites in the absence of serum. Recombinant
huMIF likewise increased the parasite survival in the absence of serum,
indicating that the parasite may use this host survival factor to resist its own
death. Moreover, TvMIF-OE parasites were found to undergo significantly less
apoptosis and reactive oxygen species (ROS) generation under conditions of serum
starvation, consistent with increased survival being the result of blocking ROS
induced apoptosis. These studies demonstrated that a parasitic MIF enhances
survival under adverse conditions and defined TvMIF and huMIF as conserved
survival factors that exhibit cross talk in host-pathogen interactions.IMPORTANCE
Macrophage migration inhibitory factor (MIF) is a conserved protein found in most
eukaryotes which has been well characterized in mammals but poorly studied in
other eukaryotes. The limited analyses of MIF proteins found in unicellular
eukaryotes have focused exclusively on the effect of parasitic MIF on the
mammalian host. This was the first study to assess the function of a parasite MIF
in parasite biology. We demonstrate that the Trichomonas vaginalis MIF functions
to suppress cell death induced by apoptosis, thereby enhancing parasite survival
under adverse conditions. Our research reveals a conserved survival mechanism,
shared by a parasite and its host, and indicates a role for a conserved protein
in mediating cross talk in host-pathogen interactions.
PMID- 29946048
TI - Shigella-Induced Emergency Granulopoiesis Protects Zebrafish Larvae from
Secondary Infection.
AB - Emergency granulopoiesis is a hematopoietic program of stem cell-driven
neutrophil production used to counteract immune cell exhaustion following
infection. Shigella flexneri is a Gram-negative enteroinvasive pathogen
controlled by neutrophils. In this study, we use a Shigella-zebrafish (Danio
rerio) infection model to investigate emergency granulopoiesis in vivo We show
that stem cell-driven neutrophil production occurs in response to Shigella
infection and requires macrophage-independent signaling by granulocyte colony
stimulating factor (Gcsf). To test whether emergency granulopoiesis can function
beyond homoeostasis to enhance innate immunity, we developed a reinfection assay
using zebrafish larvae that have not yet developed an adaptive immune system.
Strikingly, larvae primed with a sublethal dose of Shigella are protected against
a secondary lethal dose of Shigella in a type III secretion system (T3SS)
dependent manner. Collectively, these results highlight a new role for emergency
granulopoiesis in boosting host defense and demonstrate that zebrafish larvae can
be a valuable in vivo model to investigate innate immune
memory.IMPORTANCEShigella is an important human pathogen of the gut. Emergency
granulopoiesis is the enhanced production of neutrophils by hematopoietic stem
and progenitor cells (HSPCs) upon infection and is widely considered a
homoeostatic mechanism for replacing exhausted leukocytes. In this study, we
developed a Shigella-zebrafish infection model to investigate stem cell-driven
emergency granulopoiesis. We discovered that zebrafish initiate granulopoiesis in
response to Shigella infection, via macrophage-independent signaling of
granulocyte colony-stimulating factor (Gcsf). Strikingly, larvae primed with a
sublethal dose of Shigella are protected against a secondary lethal dose of
Shigella in a type III secretion system (T3SS)-dependent manner. Taken together,
we show that zebrafish infection can be used to capture Shigella-mediated stem
cell-driven granulopoiesis and provide a new model system to study stem cell
biology in vivo Our results also highlight the potential of manipulating stem
cell-driven granulopoiesis to boost innate immunity and combat infectious
disease.
PMID- 29946050
TI - In Vitro Reconstitution of Functional Type III Protein Export and Insights into
Flagellar Assembly.
AB - The type III secretion system (T3SS) forms the functional core of injectisomes,
protein transporters that allow bacteria to deliver virulence factors into their
hosts for infection, and flagella, which are critical for many pathogens to reach
the site of infection. In spite of intensive genetic and biochemical studies, the
T3SS protein export mechanism remains unclear due to the difficulty of accurate
measurement of protein export in vivo Here, we developed an in vitro flagellar
T3S protein transport assay system using an inverted cytoplasmic membrane vesicle
(IMV) for accurate and controlled measurements of flagellar protein export. We
show that the flagellar T3SS in the IMV fully retains export activity. The
flagellar hook was constructed inside the lumen of the IMV by adding purified
component proteins externally to the IMV solution. We reproduced the hook length
control and export specificity switch in the IMV consistent with that seen in the
native cell. Previous in vivo analyses showed that flagellar protein export is
driven by proton motive force (PMF) and facilitated by ATP hydrolysis by FliI, a
T3SS-specific ATPase. Our in vitro assay recapitulated these previous in vivo
observations but furthermore clearly demonstrated that even ATP hydrolysis by
FliI alone can drive flagellar protein export. Moreover, this assay showed that
addition of the FliH2/FliI complex to the assay solution at a concentration
similar to that in the cell dramatically enhanced protein export, confirming that
the FliH2/FliI complex in the cytoplasm is important for effective protein
transport.IMPORTANCE The type III secretion system (T3SS) is the functional core
of the injectisome, a bacterial protein transporter used to deliver virulence
proteins into host cells, and bacterial flagella, critical for many pathogens.
The molecular mechanism of protein transport is still unclear due to difficulties
in accurate measurements of protein transport under well-controlled conditions in
vivo We succeeded in developing an in vitro transport assay system of the
flagellar T3SS using inverted membrane vesicles (IMVs). Flagellar hook formation
was reproduced in the IMV, suggesting that the export apparatus in the IMV
retains a protein transport activity similar to that in the cell. Using this
system, we revealed that ATP hydrolysis by the T3SS ATPase can drive protein
export without PMF.
PMID- 29946049
TI - The Rickettsial Ankyrin Repeat Protein 2 Is a Type IV Secreted Effector That
Associates with the Endoplasmic Reticulum.
AB - Strains of Rickettsia rickettsii, the tick-borne agent of Rocky Mountain spotted
fever, vary considerably in virulence. Genomic comparisons of R. rickettsii
strains have identified a relatively small number of genes divergent in an
avirulent strain. Among these is one annotated as Rickettsia ankyrin repeat
protein 2 (RARP-2). Homologs of RARP-2 are present in all strains of R.
rickettsii, but the protein in the avirulent strain Iowa contains a large
internal deletion relative to the virulent Sheila Smith strain. RARP-2 is
secreted in a type IV secretion system-dependent manner and exposed to the host
cell cytosol. RARP-2 of Sheila Smith colocalizes with multilamellar membranous
structures bearing markers of the endoplasmic reticulum (ER), whereas the Iowa
protein shows no colocalization with host cell organelles and evidence of
proteolytic degradation is detected. Overexpression of Sheila Smith RARP-2 in R.
rickettsii Iowa converts this avirulent strain's typically nonlytic or opaque
plaque type to a lytic plaque phenotype similar to that of the virulent Sheila
Smith strain. Mutation of a predicted proteolytic active site of Sheila Smith
RARP-2 abolished the lytic plaque phenotype but did not eliminate association
with host membrane. RARP-2 is thus a type IV secreted effector and released from
the rickettsiae into the host cytosol to modulate host processes during
infection. Overexpression of Sheila Smith RARP-2 did not, however, restore the
virulence of the Iowa strain in a guinea pig model, likely due to the
multifactorial nature of rickettsial virulence.IMPORTANCE Members of the genus
Rickettsia are obligate intracellular bacteria that exhibit a range of virulence
from harmless endosymbionts of arthropods to the etiologic agents of severe
disease. Despite the growing number of available genomes, little is known
regarding virulence determinants of rickettsiae. Here, we have characterized an
ankyrin repeat-containing protein, RARP-2, which differs between a highly
virulent and an avirulent strain of R. rickettsii, the agent of Rocky Mountain
spotted fever. RARP-2 is secreted by a type IV secretion system into the cytosol
of the host cell, where it interacts with and manipulates the structure of the
endoplasmic reticulum. RARP-2 from the avirulent strain is truncated by the loss
of seven of 10 ankyrin repeat units but, although secreted, fails to alter ER
structure. Recognition of those rickettsial factors associated with virulence
will facilitate understanding of regional and strain-specific variation in
severity of disease.
PMID- 29946051
TI - Ongoing Transposon-Mediated Genome Reduction in the Luminous Bacterial Symbionts
of Deep-Sea Ceratioid Anglerfishes.
AB - Diverse marine fish and squid form symbiotic associations with extracellular
bioluminescent bacteria. These symbionts are typically free-living bacteria with
large genomes, but one known lineage of symbionts has undergone genomic reduction
and evolution of host dependence. It is not known why distinct evolutionary
trajectories have occurred among different luminous symbionts, and not all known
lineages previously had genome sequences available. In order to better understand
patterns of evolution across diverse bioluminescent symbionts, we de novo
sequenced the genomes of bacteria from a poorly studied interaction, the
extracellular symbionts from the "lures" of deep-sea ceratioid anglerfishes. Deep
sea anglerfish symbiont genomes are reduced in size by about 50% compared to free
living relatives. They show a striking convergence of genome reduction and loss
of metabolic capabilities with a distinct lineage of obligately host-dependent
luminous symbionts. These losses include reductions in amino acid synthesis
pathways and abilities to utilize diverse sugars. However, the symbiont genomes
have retained a number of categories of genes predicted to be useful only outside
the host, such as those involved in chemotaxis and motility, suggesting that they
may persist in the environment. These genomes contain very high numbers of
pseudogenes and show massive expansions of transposable elements, with
transposases accounting for 28 and 31% of coding sequences in the symbiont
genomes. Transposon expansions appear to have occurred at different times in each
symbiont lineage, indicating either independent evolutions of reduction or
symbiont replacement. These results suggest ongoing genomic reduction in
extracellular luminous symbionts that is facilitated by transposon
proliferations.IMPORTANCE Many female deep-sea anglerfishes possess a "lure"
containing luminous bacterial symbionts. Here we show that unlike most luminous
symbionts, these bacteria are undergoing an evolutionary transition toward small
genomes with limited metabolic capabilities. Comparative analyses of the symbiont
genomes indicate that this transition is ongoing and facilitated by transposon
expansions. This transition may have occurred independently in different symbiont
lineages, although it is unclear why. Genomic reduction is common in bacteria
that only live within host cells but less common in bacteria that, like
anglerfish symbionts, live outside host cells. Since multiple evolutions of
genomic reduction have occurred convergently in luminous bacteria, they make a
useful system with which to understand patterns of genome evolution in
extracellular symbionts. This work demonstrates that ecological factors other
than an intracellular lifestyle can lead to dramatic gene loss and evolutionary
changes and that transposon expansions may play important roles in this process.
PMID- 29946052
TI - Long-Term In Vitro Culture of the Syphilis Spirochete Treponema pallidum subsp.
pallidum.
AB - Investigation of Treponema pallidum subsp. pallidum, the spirochete that causes
syphilis, has been hindered by an inability to culture the organism continuously
in vitro despite more than a century of effort. In this study, long-term
logarithmic multiplication of T. pallidum was attained through subculture every 6
to 7 days and periodic feeding using a modified medium (T. pallidum culture
medium 2 [TpCM-2]) with a previously described microaerobic, rabbit epithelial
cell coincubation system. Currently, cultures have maintained continuous growth
for over 6 months with full retention of viability as measured by motility and
rabbit infectivity. This system has been applied successfully to the well-studied
Nichols strain of T. pallidum, as well as to two recent syphilis isolates, UW231B
and UW249B. Light microscopy and cryo-electron microscopy showed that in vitro
cultured T. pallidum retains wild-type morphology. Further refinement of this
long-term subculture system is expected to facilitate study of the physiological,
genetic, pathological, immunologic, and antimicrobial susceptibility properties
of T. pallidum subsp. pallidum and closely related pathogenic Treponema species
and subspecies.IMPORTANCE Syphilis, a sexually transmitted disease with a global
distribution, is caused by a spiral-shaped bacterium called Treponema pallidum
subspecies pallidum Previously, T. pallidum was one of the few major bacterial
pathogens that had not been cultured long-term in vitro (in a test tube), greatly
hindering efforts to better understand this organism and the disease that it
causes. In this article, we report the successful long-term cultivation of T.
pallidum in a tissue culture system, a finding that is likely to enhance our
ability to obtain new information applicable to the diagnosis, treatment, and
prevention of syphilis.
PMID- 29946053
TI - A Novel Adaptation Mechanism Underpinning Algal Colonization of a Nuclear Fuel
Storage Pond.
AB - Geochemical analyses alongside molecular techniques were used to characterize the
microbial ecology and biogeochemistry of an outdoor spent nuclear fuel storage
pond at Sellafield, United Kingdom, that is susceptible to seasonal algal blooms
that cause plant downtime. 18S rRNA gene profiling of the filtered biomass
samples showed the increasing dominance of a species closely related to the alga
Haematococcus pluvialis, alongside 16S rRNA genes affiliated with a diversity of
freshwater bacteria, including Proteobacteria and Cyanobacteria High retention of
137Cs and 90Sr on pond water filters coincided with high levels of microbial
biomass in the pond, suggesting that microbial colonization may have an important
control on radionuclide fate in the pond. To interpret the unexpected dominance
of Haematococcus species during bloom events in this extreme environment, the
physiological response of H. pluvialis to environmentally relevant ionizing
radiation doses was assessed. Irradiated laboratory cultures produced significant
quantities of the antioxidant astaxanthin, consistent with pigmentation observed
in pond samples. Fourier transform infrared (FT-IR) spectroscopy suggested that
radiation did not have a widespread impact on the metabolic fingerprint of H.
pluvialis in laboratory experiments, despite the 80-Gy dose. This study suggests
that the production of astaxanthin-rich encysted cells may be related to the
preservation of the Haematococcus phenotype, potentially allowing it to survive
oxidative stress arising from radiation doses associated with the spent nuclear
fuel. The oligotrophic and radiologically extreme conditions in this environment
do not prevent extensive colonization by microbial communities, which play a
defining role in controlling the biogeochemical fate of major radioactive species
present.IMPORTANCE Spent nuclear fuel is stored underwater in large ponds prior
to processing and disposal. Such environments are intensively radioactive but can
be colonized by microorganisms. Colonization of such inhospitable radioactive
ponds is surprising, and the survival mechanisms that microbes use is of
fundamental interest. It is also important to study these unusual ecosystems, as
microbes growing in the pond waters may accumulate radionuclides present in the
waters (for bioremediation applications), while high cell loads can hamper
management of the ponds due to poor visibility. In this study, an outdoor pond at
the U.K. Sellafield facility was colonized by a seasonal bloom of microorganisms,
able to accumulate high levels of 137Cs and 90Sr and dominated by the alga
Haematococcus This organism is not normally associated with deep water bodies,
but it can adapt to radioactive environments via the production of the pigment
astaxanthin, which protects the cells from radiation damage.
PMID- 29946054
TI - Plasma PCSK9 correlates with apoB-48-containing triglyceride-rich lipoprotein
production in men with insulin resistance.
AB - Intestinal triglyceride (TG)-rich lipoproteins (TRLs) are important in the
pathogenesis of atherosclerosis in insulin resistance (IR). We investigated the
association of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9)
concentrations with apoB-48-containing TRL metabolism in 148 men displaying
various degrees of IR by measuring in vivo kinetics of TRL apoB-48 during a
constant-fed state after a primed-constant infusion of L-[5,5,5-D3]leucine.
Plasma PCSK9 concentrations positively correlated with TRL apoB-48 pool size (r =
0.31, P = 0.0002) and production rate (r = 0.24, P = 0.008) but not the
fractional catabolic rate (r = -0.04, P = 0.6). Backward stepwise multiple linear
regression analysis identified PCSK9 concentrations as a positive predictor of
TRL apoB-48 production rate (standard beta = +0.20, P = 0.007) independent of
BMI, age, T2D/metformin use, dietary fat intake during the kinetic study, and
fasting concentrations of TGs, insulin, glucose, LDL cholesterol, or C-reactive
protein. We also assessed intestinal expression of key genes involved in
chylomicron processing from duodenal samples of 71 men. Expression of PCSK9 and
HMG-CoAR genes was positively associated (r = 0.43, P = 0.002). These results
support PCSK9 association with intestinal secretion and plasma overaccumulation
of TRL apoB-48 in men with IR.
PMID- 29946055
TI - Host lipidome analysis during rhinovirus replication in HBECs identifies
potential therapeutic targets.
AB - In patients with asthma or chronic obstructive pulmonary disease, rhinovirus (RV)
infections can provoke acute worsening of disease, and limited treatment options
exist. Viral replication in the host cell induces significant remodeling of
intracellular membranes, but few studies have explored this mechanistically or as
a therapeutic opportunity. We performed unbiased lipidomic analysis on human
bronchial epithelial cells infected over a 6 h period with the RV-A1b strain of
RV to determine changes in 493 distinct lipid species. Through pathway and
network analysis, we identified temporal changes in the apparent activities of a
number of lipid metabolizing and signaling enzymes. In particular, analysis
highlighted FA synthesis and ceramide metabolism as potential anti-rhinoviral
targets. To validate the importance of these enzymes in viral replication, we
explored the effects of commercially available enzyme inhibitors upon RV-A1b
infection and replication. Ceranib-1, D609, and C75 were the most potent
inhibitors, which confirmed that FAS and ceramidase are potential inhibitory
targets in rhinoviral infections. More broadly, this study demonstrates the
potential of lipidomics and pathway analysis to identify novel targets to treat
human disorders.
PMID- 29946057
TI - Open source modules for tracking animal behavior and closed-loop stimulation
based on Open Ephys and Bonsai.
AB - OBJECTIVE: A major goal in systems neuroscience is to determine the causal
relationship between neural activity and behavior. To this end, methods that
combine monitoring neural activity, behavioral tracking, and targeted
manipulation of neurons in closed-loop are powerful tools. However, commercial
systems that allow these types of experiments are usually expensive and rely on
non-standardized data formats and proprietary software which may hinder user
modifications for specific needs. In order to promote reproducibility and data
sharing in science, transparent software and standardized data formats are an
advantage. Here, we present an open source, low-cost, adaptable, and easy to set
up system for combined behavioral tracking, electrophysiology, and closed-loop
stimulation. APPROACH: Based on the Open Ephys system (www.open-ephys.org) we
developed multiple modules to include real-time tracking and behavior-based
closed-loop stimulation. We describe the equipment and provide a step-by-step
guide to set up the system. Combining the open source software Bonsai (bonsai
rx.org) for analyzing camera images in real time with the newly developed modules
in Open Ephys, we acquire position information, visualize tracking, and perform
tracking-based closed-loop stimulation experiments. To analyze the acquired data
we provide an open source file reading package in Python. MAIN RESULTS: The
system robustly visualizes real-time tracking and reliably recovers tracking
information recorded from a range of sampling frequencies (30-1000 Hz). We
combined electrophysiology with the newly-developed tracking modules in Open
Ephys to record place cell and grid cell activity in the hippocampus and in the
medial entorhinal cortex, respectively. Moreover, we present a case in which we
used the system for closed-loop optogenetic stimulation of entorhinal grid cells.
SIGNIFICANCE: Expanding the Open Ephys system to include animal tracking and
behavior-based closed-loop stimulation extends the availability of high-quality,
low-cost experimental setup within standardized data formats serving the
neuroscience community.
PMID- 29946056
TI - Disrupted cholesterol metabolism promotes age-related photoreceptor
neurodegeneration.
AB - Photoreceptors have high intrinsic metabolic demand and are exquisitely sensitive
to metabolic perturbation. In addition, they shed a large portion of their outer
segment lipid membranes in a circadian manner, increasing the metabolic burden on
the outer retina associated with the resynthesis of cell membranes and disposal
of the cellular cargo. Here, we demonstrate that deletion of both ABCA1 and ABCG1
in rod photoreceptors leads to age-related accumulation of cholesterol
metabolites in the outer retina, photoreceptor dysfunction, degeneration of rod
outer segments, and ultimately blindness. A high-fat diet significantly
accelerates rod neurodegeneration and vision loss, further highlighting the role
of lipid homeostasis in regulating photoreceptor neurodegeneration and vision.
PMID- 29946058
TI - Pediatric Condition Falsification Misdiagnosed by Misjudged Weight Growth from
the Curve of Measured Weights.
AB - BACKGROUND Pediatric condition falsification (PCF) is a rare form of child abuse
in which a caregiver fabricates or induces illness in the child. The diagnosis is
difficult and controversial and can easily include false positives. CASE REPORT A
boy, 3.18 kg birthweight (P25 curve), lost weight between age 56 to120 days. Cow
milk allergy was suspected, feeding was changed to elementary formula, and he
started catch-up weight growth while remaining significantly underweight. His
pediatrician continuously interpreted his low weight as insufficient growth,
despite prescribing 3 times the normal caloric intake, concluded that the mother
purposely malnourished her son, diagnosed PCF, and the boy was separated from his
family (days 502-755 of age). PCF was confirmed by 2 other pediatricians and 3
child protection physicians and was supported by 4 child protection agencies and
6 judges. However, proper analysis of the weight growth (kg/year) from the weight
curve showed a normal weight gain. Beyond 120 days of age, weight gain at home
was significantly above normal (during 347-489 days: 6.2 versus 3 kg/year of the
P50). He reached P25 again at around 516 days. CONCLUSIONS The question "How
could so many physicians misjudge weight gain?" has scientific and sociologic
aspects. Scientifically, low weight was wrongly interpreted as insufficient
weight growth, requiring that physicians learn how to assess weight gain from
weight curves. Sociologically, physicians seem to follow a diagnosis made by a
colleague without proper evaluation. Arguments provided by the parents against
this diagnosis seemed to be neglected. Confirmation bias occurs when any
information against PCF is disregarded.
PMID- 29946059
TI - Platelet-to-Lymphocyte Ratio as a New Predictive Index of Neurological Outcomes
in Patients with Acute Intracranial Hemorrhage: A Retrospective Study.
AB - BACKGROUND Systemic inflammation plays a critical role in the pathophysiological
process of intracranial hemorrhage (ICH). Recently, the platelet-to-lymphocyte
ratio (PLR) has become a research focus that indicates inflammation in various
diseases. Thus, this study aimed to investigate the predictive value of PLR in
patients with acute ICH. MATERIAL AND METHODS This study was performed in a
single teaching hospital. Glasgow coma scale at hospital discharge (GCSdis) and
modified Rankin score (MRS) at 6 months were recorded as short-term and long-term
neurological outcomes. Ordered and binary logistic regression methods were used
to explore the associations. RESULTS Finally, data on 183 ICH patients were
included. A knot of PLR around 100 was detected and applied in the extended
ordered logistic regression models. For PLR >100, PLR on ICU admission was
significantly associated with worse GCSdis (from Model 1: OR: 1.004, 95% CI 1.001
1.007 to Model 4: OR: 1.006, 95% CI 1.002-1.009) while the PLR on Emergency
Department (ED) admission was insignificant. For PLR <=100, neither the PLR on
ICU or ED admission was associated with GCSdis level. In the quartile grouping
analysis, PLR Q2 was used as a reference level. Both Q3 and Q4 on ICU admission
were significantly associated with lower GCSdis level (OR, 3.30; 95%CI 1.38-7.88;
and OR, 3.79; 95%CI 1.54-9.33, respectively), while Q1 was insignificant. All 4
quartiles of PLR on ED admission were not associated with GCSdis. CONCLUSIONS
Only higher PLR value on ICU admission but not on ED admission was associated
with worse GCSdis.
PMID- 29946060
TI - Estimating spatiotemporally varying malaria reproduction numbers in a near
elimination setting.
AB - In 2016 the World Health Organization identified 21 countries that could
eliminate malaria by 2020. Monitoring progress towards this goal requires
tracking ongoing transmission. Here we develop methods that estimate individual
reproduction numbers and their variation through time and space. Individual
reproduction numbers, Rc, describe the state of transmission at a point in time
and differ from mean reproduction numbers, which are averages of the number of
people infected by a typical case. We assess elimination progress in El Salvador
using data for confirmed cases of malaria from 2010 to 2016. Our results
demonstrate that whilst the average number of secondary malaria cases was below
one (0.61, 95% CI 0.55-0.65), individual reproduction numbers often exceeded one.
We estimate a decline in Rc between 2010 and 2016. However we also show that if
importation is maintained at the same rate, the country may not achieve malaria
elimination by 2020.
PMID- 29946061
TI - Simultaneous hyperaccumulation of nickel and cobalt in the tree Glochidion cf.
sericeum (Phyllanthaceae): elemental distribution and chemical speciation.
AB - Hyperaccumulation is generally highly specific for a single element, for example
nickel (Ni). The recently-discovered hyperaccumulator Glochidion cf. sericeum
(Phyllanthaceae) from Malaysia is unusual in that it simultaneously accumulates
nickel and cobalt (Co) with up to 1500 MUg g-1 foliar of both elements. We set
out to determine whether distribution and associated ligands for Ni and Co
complexation differ in this species. We postulated that Co hyperaccumulation
coincides with Ni hyperaccumulation operating on similar physiological pathways.
However, the ostensibly lower tolerance for Co at the cellular level results in
the exudation of Co on the leaf surface in the form of lesions. The formation of
such lesions is akin to phytotoxicity responses described for manganese (Mn).
Hence, in contrast to Ni, which is stored principally inside the foliar epidermal
cells, the accumulation response to Co consists of an extracellular mechanism.
The chemical speciation of Ni and Co, in terms of the coordinating ligands
involved and principal oxidation state, is similar and associated with carboxylic
acids (citrate for Ni and tartrate or malate for Co) and the hydrated metal ion.
Some oxidation to Co3+, presumably on the surface of leaves after exudation, was
observed.
PMID- 29946062
TI - Recovery of coral assemblages despite acute and recurrent disturbances on a South
Central Pacific reef.
AB - Coral reefs are increasingly threatened by various types of disturbances, and
their recovery is challenged by accelerating, human-induced environmental
changes. Recurrent disturbances reduce the pool of mature adult colonies of reef
building corals and undermine post-disturbance recovery from newly settled
recruits. Using a long-term interannual data set, we show that coral assemblages
on the reef slope of Moorea, French Polynesia, have maintained a high capacity to
recover despite a unique frequency of large-scale disturbances which, since the
1990s, have caused catastrophic declines in coral cover and abundance. In 2014,
only four years after one of the most extreme cases of coral decline documented,
abundance of juvenile and adult colonies had regained or exceeded pre-disturbance
levels, and no phase-shift to macroalgal dominance was recorded. This rapid
recovery has been achieved despite constantly low coral recruitment rates,
suggesting a high post-disturbance survivorship of recruits. However, taxonomic
differences in coral susceptibility to disturbances and contrasting recovery
trajectories have resulted in changes in the relative composition of species. In
the present context of global coral reef decline, our study establishes a new
benchmark for the capacity of certain benthic reef communities to sustain and
recover their coral cover from repeated, intense disturbances.
PMID- 29946063
TI - Consistent signatures of selection from genomic analysis of pairs of temporal and
spatial Plasmodium falciparum populations from The Gambia.
AB - Genome sequences of 247 Plasmodium falciparum isolates collected in The Gambia in
2008 and 2014 were analysed to identify changes possibly related to the scale-up
of antimalarial interventions that occurred during this period. Overall, there
were 15 regions across the genomes with signatures of positive selection. Five of
these were sweeps around known drug resistance and antigenic loci. Signatures at
antigenic loci such as thrombospodin related adhesive protein (Pftrap) were most
frequent in eastern Gambia, where parasite prevalence and transmission remain
high. There was a strong temporal differentiation at a non-synonymous SNP in a
cysteine desulfarase (Pfnfs) involved in iron-sulphur complex biogenesis. During
the 7-year period, the frequency of the lysine variant at codon 65 (Pfnfs-Q65K)
increased by 22% (10% to 32%) in the Greater Banjul area. Between 2014 and 2015,
the frequency of this variant increased by 6% (20% to 26%) in eastern Gambia.
IC50 for lumefantrine was significantly higher in Pfnfs-65K isolates. This is
probably the first evidence of directional selection on Pfnfs or linked loci by
lumefantrine. Given the declining malaria transmission, the consequent loss of
population immunity, and sustained drug pressure, it is important to monitor
Gambian P. falciparum populations for further signs of adaptation.
PMID- 29946064
TI - Three-terminal RGB full-color OLED pixels for ultrahigh density displays.
AB - In recent years, the organic light-emitting diode (OLED) technology has been a
rapidly evolving field of research, successfully making the transition to
commercial applications such as mobile phones and other small portable devices.
OLEDs provide efficient generation of light, excellent color quality, and allow
for innovative display designs, e.g., curved shapes, mechanically flexible and/or
transparent devices. Especially their self emissive nature is a highly desirable
feature for display applications. In this work, we demonstrate an approach for
full-color OLED pixels that are fabricated by vertical stacking of a red-, green
, and blue-emitting unit. Each unit can be addressed separately which allows for
efficient generation of every color that is accessible by superpositioning the
spectra of the individual emission units. Here, we use a combination of time
division multiplexing and pulse width modulation to achieve efficient color
mixing. The presented device design requires only three independently addressable
electrodes, simplifying both fabrication and electrical driving. The device is
built in a top-emission geometry, which is highly desirable for display
fabrication as the pixel can be directly deposited onto back-plane electronics.
Despite the top-emission design and the application of three silver layers within
the device, there is only a minor color shift even for large viewing angles. The
color space spanned by the three emission sub-units exceeds the sRGB space,
providing more saturated green/yellow/red colors. Furthermore, the electrical
performance of each individual unit is on par with standard single emission unit
OLEDs, showing very low leakage currents and achieving brightness levels above
1000 cd/m2 at moderate voltages of around 3-4 V.
PMID- 29946065
TI - C3a triggers formation of sub-retinal pigment epithelium deposits via the
ubiquitin proteasome pathway.
AB - The mechanisms that connect complement system activation and basal deposit
formation in early stages of age-related macular degeneration (AMD) are
insufficiently understood, which complicates the design of efficient therapies to
prevent disease progression. Using human fetal (hf) retinal pigment epithelial
(RPE) cells, we have established an in vitro model to investigate the effect of
complement C3a on RPE cells and its role in the formation of sub-RPE deposits.
The results of these studies revealed that C3a produced after C3 activation is
sufficient to induce the formation of sub-RPE deposits via complement-driven
proteasome inhibition. C3a binds the C3a receptor (C3aR), stimulates deposition
of collagens IV and VI underneath the RPE, and impairs the extracellular matrix
(ECM) turnover by increased MMP-2 activity, all mediated by downregulation of the
ubiquitin proteasome pathway (UPP). The formation of basal deposits can be
prevented by the addition of a C3aR antagonist, which restores the UPP activity
and ECM turnover. These findings indicate that the cell-based model can be used
to test potential therapeutic agents in vitro. The data suggest that modulation
of C3aR-mediated events could be a therapeutic approach for treatment of early
AMD.
PMID- 29946066
TI - Macrolide and phenolic metabolites from the marine-derived fungus
Paraconiothyrium sp. VK-13 with anti-inflammatory activity.
AB - Five new secondary metabolites, modiolides D-G (1-4) and 1-(2,5-dihydroxyphenyl)
3-methoxy-butan-1-one (8), one new natural product, 1-(2,5-dihydroxyphenyl)-3
hydroxybutan-1-one (7), along with three known compounds, modiolides A (5) and B
(6), and 1-(2,5-dihydroxyphenyl)-2-buten-1-one (9) were isolated from a
fermentation culture of the marine endophytic fungus Paraconiothyrium sp. VK-13.
Their chemical structures were elucidated by the NMR and MS spectroscopic
analysis as well as the modified Mosher's method. Compounds 7 and 9 inhibited the
overproduction of proinflammatory mediators NO and PGE2 in LPS-stimulated
RAW264.7 cells, with IC50 values ranging from 3.9 to 12.5 uM. The inhibitory
effects of 7 and 9 on the release of NO and PGE2 were correlated with their
significant suppression of iNOS and COX-2 protein expression, respectively.
Furthermore, both compounds 7 and 9 inhibited the mRNA expression of
proinflammatory cytokines, including TNF-alpha, IL-1beta, IL-6, and IL-12, with
IC50 values in a range of 2.4-12.5 uM.
PMID- 29946067
TI - Hypokalaemic periodic paralysis and myotonia in a patient with homozygous
mutation p.R1451L in NaV1.4.
AB - Dominantly inherited channelopathies of the skeletal muscle voltage-gated sodium
channel NaV1.4 include hypokalaemic and hyperkalaemic periodic paralysis (hypoPP
and hyperPP) and myotonia. HyperPP and myotonia are caused by NaV1.4 channel
overactivity and overlap clinically. Instead, hypoPP is caused by gating pore
currents through the voltage sensing domains (VSDs) of NaV1.4 and seldom co
exists clinically with myotonia. Recessive loss-of-function NaV1.4 mutations have
been described in congenital myopathy and myasthenic syndromes. We report two
families with the NaV1.4 mutation p.R1451L, located in VSD-IV. Heterozygous
carriers in both families manifest with myotonia and/or hyperPP. In contrast, a
homozygous case presents with both hypoPP and myotonia, but unlike carriers of
recessive NaV1.4 mutations does not manifest symptoms of myopathy or myasthenia.
Functional analysis revealed reduced current density and enhanced closed state
inactivation of the mutant channel, but no evidence for gating pore currents. The
rate of recovery from inactivation was hastened, explaining the myotonia in
p.R1451L carriers and the absence of myasthenic presentations in the homozygous
proband. Our data suggest that recessive loss-of-function NaV1.4 variants can
present with hypoPP without congenital myopathy or myasthenia and that myotonia
can present even in carriers of homozygous NaV1.4 loss-of-function mutations.
PMID- 29946068
TI - Loss of radioactivity in radiocesium-bearing microparticles emitted from the
Fukushima Dai-ichi nuclear power plant by heating.
AB - Radiocesium-bearing microparticles (CsPs) substantially made of silicate glass
are a novel form of radiocesium emitted from the broken containment vessel of
Fukushima Dai-ichi nuclear power plant. CsPs have a potential risk of internal
radiation exposure caused by inhalation. Radiation-contaminated waste including
CsPs is being burned in incinerators; therefore, this study has investigated the
responses of CsPs to heating in air. The radioactivity of CsPs gradually
decreased from 600 degrees C and was almost lost when the temperature reached
1000 degrees C. The size and spherical morphology of CsPs were almost unchanged
after heating, but cesium including radiocesium, potassium and chlorine were
lost, probably diffused away from the CsPs. Iron, zinc and tin originally
dissolved in the glass matrix were crystallized to oxide nanoparticles inside the
CsPs. When the CsPs were heated together with weathered granitic soil that is
common in Fukushima, the radiocesium released from CsPs was sorbed by the
surrounding soil. From these results, it is expected that the radioactivity of
CsPs will be lost when radiation-contaminated waste including CsPs is burned in
incinerators.
PMID- 29946069
TI - An effect of serotonergic stimulation on learning rates for rewards apparent
after long intertrial intervals.
AB - Serotonin has widespread, but computationally obscure, modulatory effects on
learning and cognition. Here, we studied the impact of optogenetic stimulation of
dorsal raphe serotonin neurons in mice performing a non-stationary, reward-driven
decision-making task. Animals showed two distinct choice strategies. Choices
after short inter-trial-intervals (ITIs) depended only on the last trial outcome
and followed a win-stay-lose-switch pattern. In contrast, choices after long ITIs
reflected outcome history over multiple trials, as described by reinforcement
learning models. We found that optogenetic stimulation during a trial
significantly boosted the rate of learning that occurred due to the outcome of
that trial, but these effects were only exhibited on choices after long ITIs.
This suggests that serotonin neurons modulate reinforcement learning rates, and
that this influence is masked by alternate, unaffected, decision mechanisms.
These results provide insight into the role of serotonin in treating psychiatric
disorders, particularly its modulation of neural plasticity and learning.
PMID- 29946071
TI - Betamethasone prevents human rhinovirus- and cigarette smoke- induced loss of
respiratory epithelial barrier function.
AB - The respiratory epithelium is a barrier against pathogens and allergens and a
target for therapy in respiratory allergy, asthma and chronic obstructive
pulmonary disease (COPD). We investigated barrier-damaging factors and protective
factors by real-time measurement of respiratory cell barrier integrity. Barrier
integrity to cigarette smoke extract (CSE), house dust mite (HDM) extract,
interferon-gamma (IFN-gamma) or human rhinovirus (HRV) infection alone or in
combination was assessed. Corticosteroids, lipopolysaccharide (LPS), and nasal
mucus proteins were tested for their ability to prevent loss of barrier
integrity. Real-time impedance-based measurement revealed different patterns of
CSE-, HDM-, IFN-gamma- and HRV-induced damage. When per se non-damaging
concentrations of harmful factors were combined, a synergetic effect was observed
only for CSE and HDM. Betamethasone prevented the damaging effect of HRV and CSE,
but not damage caused by HDM or IFN-gamma. Real-time impedance-based measurement
of respiratory epithelial barrier function is useful to study factors, which are
harmful or protective. The identification of a synergetic damaging effect of CSE
and HDM as well as the finding that Betamethasone protects against HRV- and CSE
induced damage may be important for asthma and COPD.
PMID- 29946070
TI - miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate
myotonic dystrophy phenotypes in mammalian models.
AB - Functional depletion of the alternative splicing factors Muscleblind-like (MBNL 1
and 2) is at the basis of the neuromuscular disease myotonic dystrophy type 1
(DM1). We previously showed the efficacy of miRNA downregulation in Drosophila
DM1 model. Here, we screen for miRNAs that regulate MBNL1 and MBNL2 in HeLa
cells. We thus identify miR-23b and miR-218, and confirm that they downregulate
MBNL proteins in this cell line. Antagonists of miR-23b and miR-218 miRNAs
enhance MBNL protein levels and rescue pathogenic missplicing events in DM1
myoblasts. Systemic delivery of these "antagomiRs" similarly boost MBNL
expression and improve DM1-like phenotypes, including splicing alterations,
histopathology, and myotonia in the HSALR DM1 model mice. These mammalian data
provide evidence for therapeutic blocking of the miRNAs that control Muscleblind
like protein expression in myotonic dystrophy.
PMID- 29946072
TI - Pulmonary Arterial Hypertension Affects the Rat Gut Microbiome.
AB - We have analysed whether pulmonary arterial hypertension (PAH) alters the rat
faecal microbiota. Wistar rats were injected with the VEGF receptor antagonist
SU5416 (20 mg/kg s.c.) and followed for 2 weeks kept in hypoxia (10% O2, PAH) or
injected with vehicle and kept in normoxia (controls). Faecal samples were
obtained and microbiome composition was determined by 16S rRNA gene sequencing
and bioinformatic analysis. No effect of PAH on the global microbiome was found
(alpha- or beta-diversity). However, PAH-exposed rats showed gut dysbiosis as
indicated by a taxonomy-based analysis. Specifically, PAH rats had a three-fold
increase in Firmicutes-to-Bacteroidetes ratio. Within the Firmicutes phylum,
there were no large changes in the relative abundance of the bacterial families
in PAH. Among Bacteroidetes, all families were less abundant in PAH. A clear
separation was observed between the control and PAH clusters based on short chain
fatty acid producing bacterial genera. Moreover, acetate was reduced in the serum
of PAH rats. In conclusion, faecal microbiota composition is altered as a result
of PAH. This misbalanced bacterial ecosystem might in turn play a
pathophysiological role in PAH by altering the immunologic, hormonal and
metabolic homeostasis.
PMID- 29946073
TI - Click communication in wild harbour porpoises (Phocoena phocoena).
AB - Social delphinids employ a vocal repertoire of clicks for echolocation and
whistles for communication. Conversely, the less social and acoustically cryptic
harbour porpoises (Phocoena phocoena) only produce narrow-band high-frequency
(NBHF) clicks with properties that appear poorly suited for communication.
Nevertheless, these small odontocetes likely mediate social interactions, such as
mate choice and mother-calf contact, with sound. Here, we deployed six tags
(DTAG3) on wild porpoises in Danish waters for a total of 96 hours to investigate
if the patterns and use of stereotyped NBHF click trains are consistent with a
communication function. We show that wild porpoises produce frequent (up to 27 *
min-1), high-repetition rate click series with repetition rates and output levels
different from those of foraging buzzes. These sounds are produced in bouts and
frequently co-occur with emission of similar sounds by nearby conspecifics,
audible on the tags for >10% of the time. These results suggest that social
interactions are more important to this species than their limited social
encounters at the surface may indicate and that these interactions are mediated
by at least two broad categories of calls composed of short, high-repetition rate
click trains that may encode information via the repetition rate of their
stereotyped NBHF clicks.
PMID- 29946075
TI - TH9 cells tackle advanced tumours.
PMID- 29946074
TI - A sensitive electrochemical immunosensor for label-free detection of Zika-virus
protein.
AB - This work, as a proof of principle, presents a sensitive and selective
electrochemical immunosensor for Zika-virus (ZIKV)-protein detection using a
functionalized interdigitated micro-electrode of gold (IDE-Au) array. A
miniaturized IDE-Au immunosensing chip was prepared via immobilization of ZIKV
specific envelop protein antibody (Zev-Abs) onto dithiobis(succinimidyl
propionate) i.e., (DTSP) functionalized IDE-Au (electrode gap/width of 10 um).
Electrochemical impedance spectroscopy (EIS) was performed to measure the
electrical response of developed sensing chip as a function of ZIKV-protein
concentrations. The results of EIS studies confirmed that sensing chip detected
ZIKV-protein selectively and exhibited a detection range from 10 pM to 1 nM and a
detection limit of 10 pM along with a high sensitivity of 12 kOmegaM-1. Such
developed ZIKV immune-sensing chip can be integrated with a miniaturized
potentiostat (MP)-interfaced with a smartphone for rapid ZIKV-infection detection
required for early stage diagnostics at point-of-care application.
PMID- 29946076
TI - New glioblastoma heterogeneity atlas - a shared resource.
PMID- 29946077
TI - Fight outcome briefly affects the reproductive fitness of male crickets.
AB - Sexual selection allows male individuals to adopt different evolutionary
strategies in mating system. In this study, we determined whether dominance
affected reproductive fitness of male crickets Velarifictorus aspersus during
both pre-copulatory and post-copulatory selection when we excluded male-male
competition. The results showed that females mated more often with male winners
only during the first 2 h after a fight when male winners were more likely to
produce courtship songs than losers. However, females did not retain the attached
spermatophores of male winners longer than those of male losers, and the
fecundity and fertilization success also did not differ significantly between
females mated different times with male winners and losers. Instead, the
fertilization success was positively correlated with male body weight. These
results suggest that a recent wining experience increases reproductive fitness of
males during pre-copulatory selection, but females may prefer larger males rather
than winners during post-copulatory selection. The incoordination between pre-
and post-copulatory selection may allow males to adopt different evolutionary
strategies in mating system.
PMID- 29946079
TI - Nonlinear associations between working hours and overwork-related cerebrovascular
and cardiovascular diseases (CCVD).
AB - Long working hours are recognized as a risk factor for cerebrovascular and
cardiovascular diseases (CCVD). We investigated the relationship between working
hours and different CCVD severity outcomes-death, disability, and illness-across
industries in Taiwan from 2006 to 2016. We applied a generalized additive mixed
model to estimate the association between working hours and the rate of each
severity outcome, adjusted for salary, unemployment rate, time, and a random
intercept. Industry-average working hours were significantly associated with each
outcome level of overwork-related CCVD, especially when monthly working hours
increased from 169 (relative risk [RR] = 1.46, 95% confidence interval [CI] 1.002
2.12) to 187 (RR = 5.73, 95% CI 3.61-9.08). Although RR trends declined after
monthly working hours exceeded 187, excess risks remained statistically
significant. Each 1-hour increase in working hours had a stronger effect on the
RR increase in death and disability than on illness. Variations in CCVD risks
existed across industries, with the highest risk in transportation and
information. Reducing working hours is essential to preventing overwork-related
CCVD, especially the more severe outcomes. We recommend further research to
address possible underreporting of less severe cases, and to explore actions to
narrow the gaps in risk across industries.
PMID- 29946078
TI - Reciprocity of social influence.
AB - Humans seek advice, via social interaction, to improve their decisions. While
social interaction is often reciprocal, the role of reciprocity in social
influence is unknown. Here, we tested the hypothesis that our influence on others
affects how much we are influenced by them. Participants first made a visual
perceptual estimate and then shared their estimate with an alleged partner. Then,
in alternating trials, the participant either revised their decisions or observed
how the partner revised theirs. We systematically manipulated the partner's
susceptibility to influence from the participant. We show that participants
reciprocated influence with their partner by gravitating toward the susceptible
(but not insusceptible) partner's opinion. In further experiments, we showed that
reciprocity is both a dynamic process and is abolished when people believed that
they interacted with a computer. Reciprocal social influence is a signaling
medium for human-to-human communication that goes beyond aggregation of evidence
for decision improvement.
PMID- 29946080
TI - Aquatic behaviour of polar bears (Ursus maritimus) in an increasingly ice-free
Arctic.
AB - Polar bears are ice-associated marine mammals that are known to swim and dive,
yet their aquatic behaviour is poorly documented. Reductions in Arctic sea ice
are clearly a major threat to this species, but understanding polar bears'
potential behavioural plasticity with respect to the ongoing changes requires
knowledge of their swimming and diving skills. This study quantified time spent
in water by adult female polar bears (n = 57) via deployment of various
instruments bearing saltwater switches, and in some case pressure sensors (79
deployments, 64.8 bear-years of data). There were marked seasonal patterns in
aquatic behaviour, with more time spent in the water during summer, when 75% of
the polar bears swam daily (May-July). Females with cubs-of-the-year spent less
time in the water than other females from den emergence (April) until mid-summer,
consistent with small cubs being vulnerable to hypothermia and drowning. Some
bears undertook notable long-distance-swims. Dive depths up to 13.9 m were
recorded, with dives >=5 m being common. The considerable swimming and diving
capacities of polar bears might provide them with tools to exploit aquatic
environments previously not utilized. This is likely to be increasingly important
to the species' survival in an Arctic with little or no persistent sea ice.
PMID- 29946081
TI - A mini-laser that can light up living tissues.
PMID- 29946082
TI - Puppies trust their mums - and humans.
PMID- 29946083
TI - Oaks last 800 years with help of DNA double take.
PMID- 29946085
TI - A short course of laxatives has long-lasting effects on microbiome.
PMID- 29946086
TI - Algorithms can foster a more democratic society.
PMID- 29946087
TI - Otzi the Iceman's tools tell a story of desperation.
PMID- 29946089
TI - Gene important in pregnancy shows evolution in action.
PMID- 29946088
TI - An eggshell mixture that sheds water and shrugs off punishment.
PMID- 29946090
TI - Genetically modified bacteria enlisted in fight against disease.
PMID- 29946092
TI - Methane leaks from US gas fields dwarf government estimates.
PMID- 29946093
TI - US-Chinese trade war puts scientists in the cross hairs.
PMID- 29946095
TI - Upstanding molecule reveals orbital wavefunction.
PMID- 29946096
TI - Mars beat Earth in the race for habitable conditions.
PMID- 29946098
TI - How the ubiquitous GPCR receptor family selectively activates signalling
pathways.
PMID- 29946099
TI - Worrying changes in Hungary.
PMID- 29946100
TI - Daring Japanese mission reaches unexplored asteroid Ryugu.
PMID- 29946101
TI - Warfarin maintenance dose Prediction for Patients undergoing heart valve
replacement- a hybrid model with genetic algorithm and Back-Propagation neural
network.
AB - Warfarin is the most recommended anticoagulant drug for patients undergoing heart
valve replacement. However, due to the narrow therapeutic window and individual
dose, the use of warfarin needs more advanced technology. We used the data
collected from a multi-central registered clinical system all over China about
the patients who have undergone heart valve replacement, subsequently divided
into three groups (training group: 10673 cases; internal validation group: 3558
cases; external validation group: 1463 cases) in order to construct a hybrid
model with genetic algorithm and Back-Propagation neural network (BP-GA), For
testing the model's prediction accuracy, we used Mean absolute error (MAE), Root
mean squared error (RMSE) and the ideal predicted percentage of total and dose
subgroups. In results, whether in internal or in external validation group, the
total ideal predicted percentage was over 58% while the intermediate dose
subgroup manifested the best. Moreover, it showed higher prediction accuracy,
lower MAE value and lower RMSE value in the external validation group than that
in the internal validation group (p < 0.05). In conclusion, BP-GA model is
promising to predict warfarin maintenance dose.
PMID- 29946102
TI - Magnetostratigraphic dating of the hominin occupation of Bailong Cave, central
China.
AB - Intermontane basins in the southern piedmont of the Qinling Mountains are
important sources of information on hominin occupation and settlement, and
provide an excellent opportunity to study early human evolution and behavioral
adaptation. Here, we present the results of a detailed magnetostratigraphic
investigation of the sedimentary sequence of hominin-bearing Bailong Cave in
Yunxi Basin, central China. Correlation to the geomagnetic polarity time scale
was achieved using previously published biostratigraphy, 26Al/10Be burial dating,
and coupled electron spin resonance (ESR) and U-series dating. The Bailong Cave
hominin-bearing layer is dated to the early Brunhes Chron, close to the Matuyama
Brunhes geomagnetic reversal at 0.78 Ma. Our findings, coupled with other
records, indicate the flourishing of early humans in mainland East Asia during
the Mid-Pleistocene climate transition (MPT). This suggests that early humans
were adapted to diverse and variable environments over a broad latitudinal range
during the MPT, from temperate northern China to subtropical southern China.
PMID- 29946103
TI - An antifungal polyketide associated with horizontally acquired genes supports
symbiont-mediated defense in Lagria villosa beetles.
AB - Microbial symbionts are often a source of chemical novelty and can contribute to
host defense against antagonists. However, the ecological relevance of chemical
mediators remains unclear for most systems. Lagria beetles live in symbiosis with
multiple strains of Burkholderia bacteria that protect their offspring against
pathogens. Here, we describe the antifungal polyketide lagriamide, and provide
evidence supporting that it is produced by an uncultured symbiont, Burkholderia
gladioli Lv-StB, which is dominant in field-collected Lagria villosa.
Interestingly, lagriamide is structurally similar to bistramides, defensive
compounds found in marine tunicates. We identify a gene cluster that is probably
involved in lagriamide biosynthesis, provide evidence for horizontal acquisition
of these genes, and show that the naturally occurring symbiont strains on the egg
are protective in the soil environment. Our findings highlight the potential of
microbial symbionts and horizontal gene transfer as influential sources of
ecological innovation.
PMID- 29946105
TI - Harmony and heresy of an L-type calcium channel inhibitor: suppression of cocaine
seeking via increased dopamine transmission in the nucleus accumbens.
PMID- 29946104
TI - Opposing actions of CRF-R1 and CB1 receptors on VTA-GABAergic plasticity
following chronic exposure to ethanol.
AB - Dopamine neurons in the ventral tegmental area (VTA) influence learned behaviors
and neuropsychiatric diseases including addiction. The stress peptide
corticotrophin-releasing factor (CRF) contributes to relapse to drug and alcohol
seeking following withdrawal, although the cellular actions are poorly
understood. In this study, we show that presynaptic CRF type 1 receptors (CRF-R1)
potentiate GABA release onto mouse VTA dopamine neurons via a PKC-Ca2+ signaling
mechanism. In naive animals, activation of CRF-R1 by bath application of CRF or
ethanol enhanced GABAA inhibitory postsynaptic currents (IPSCs). Following 3 days
of withdrawal from four weekly cycles of chronic intermittent ethanol (CIE) vapor
exposure, spontaneous IPSC frequency was enhanced while CRF and ethanol
potentiation of IPSCs was intact. However, withdrawal for 3 weeks or more was
associated with reduced spontaneous IPSC frequency and diminished CRF and ethanol
responses. Long-term withdrawal was also accompanied by decreased sensitivity to
the CB1 receptor agonist WIN55212 as well as greatly enhanced sensitivity to the
CB1 antagonist AM251. Inclusion of BAPTA in the internal recording solution
restored the responsiveness to CRF or ethanol and reduced the potentiating
actions of AM251. Together, these data suggest that GABAA inhibition of VTA
dopamine neurons is regulated by presynaptic actions of CRF and endocannabinoids
and that long-term withdrawal from CIE treatment enhances endocannabinoid
mediated inhibition, thereby suppressing CRF facilitation of GABA release. Such
findings have implications for understanding the impact of chronic alcohol on
stress-related, dopamine-mediated alcohol-seeking behaviors.
PMID- 29946106
TI - Efficacy, tolerability, and cognitive effects of deep transcranial magnetic
stimulation for late-life depression: a prospective randomized controlled trial.
AB - Late-life depression (LLD) is a growing worldwide problem due to demographic
changes, with limited treatment options due to high rates of pharmacotherapy
adverse effects, accessibility of psychotherapy, and tolerability of
electroconvulsive therapy. Novel neuromodulation techniques, such as repetitive
transcranial magnetic stimulation (rTMS), may overcome these limitations. The
objective of this study is to determine the efficacy, tolerability, and cognitive
effects of high-dose deep rTMS in LLD. In this study we randomized older adults
between 60 and 85 years old with major depressive disorder (MDD) to sham or
active deep rTMS (H1 coil, 6012 pulses, 18 Hz, 120% of resting motor threshold)
delivered over the dorsolateral and ventrolateral prefrontal cortex 5 days per
week over 4 weeks. Our primary outcome was remission of depression in an
intention-to-treat analysis. We also assessed change in cognitive functioning
with rTMS treatment and tolerability based on adverse effects. Fifty-two
participants were randomized to active (n = 25) or sham H1 coil (n = 27).
Remission rate was significantly higher with active than sham rTMS (40.0% vs
14.8%) with a number needed to treat of 4.0 (95% CI: 2.1-56.5). There was no
change on any measure of executive function and no serious adverse events.
Adverse effect profiles were similar between active and sham rTMS, except for
reports of pain being significantly more common in the active condition (16.0% vs
0%). High-dose deep rTMS appears to be safe, well tolerated, and efficacious in
the treatment of LLD.
PMID- 29946107
TI - Discrete patterns of cortical thickness in youth with bipolar disorder
differentially predict treatment response to quetiapine but not lithium.
AB - The need for treatment response predictive biomarkers is being increasingly
recognized in children and adolescents with psychiatric disorders. Structural
gray matter abnormalities as a predictor of treatment outcome in pediatric
bipolar disorder have not been systematically investigated, especially early in
the illness course. With a prospective longitudinal study design, the present
study enrolled 52 bipolar adolescents with no history of treatment with mood
stabilizers or a therapeutic dose of antipsychotic drugs and 31 healthy controls.
Patients were randomly assigned to treatment with quetiapine or lithium after
pretreatment data collection. A hierarchical cluster analysis was performed using
pretreatment cortical thickness data that identified two discrete patient
subgroups. Compared to healthy subjects, patients in subgroup 1 (n = 16) showed
widespread greater cortical thickness mainly across heteromodal cortex but also
involving some regions of unimodal cortex, while those in subgroup 2 (n = 36)
showed regional cortical thinning mainly in superior temporal and superior
parietal regions. Patients within subgroup 1 showed a significantly higher
response rate to quetiapine than those in subgroup 2 (100% vs 53%). No
statistically significant difference was found in lithium response rate between
the patient subgroups (63% vs 53%). Pretreatment clinical ratings and
neuropsychological data did not differ across subgroups. Our findings suggest the
existence of distinct and clinically relevant subgroups of pediatric bipolar
patients, as defined by pattern of cortical thickness. These groups appear to
differentially respond to antipsychotic treatment-notably with greater cortical
thickness relative to controls predicting better treatment response.
PMID- 29946109
TI - Ronald R Fieve.
PMID- 29946110
TI - CNS relapse in patients with DLBCL treated with lenalidomide plus R-CHOP
(R2CHOP): analysis from two phase 2 studies.
AB - Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is
a devastating event occurring in ~ 5% of patients treated with R-CHOP. We
hypothesized that adding lenalidomide to R-CHOP (R2CHOP) may decrease the risk of
CNS relapse. We analyzed records for patients with DLBCL from two R2CHOP trials.
We assessed variables pertinent to the CNS-International Prognostic Index (CNS
IPI) scoring system and classified patients into groups of low, intermediate, and
high risk of CNS relapse. The 2-year CNS relapse rate for each risk group was
estimated using the Kaplan-Meier method and compared with reported rates in
cohorts treated with contemporary chemoimmunotherapy. A total of 136 patients
were included. Mean age was 65 and median follow-up was 48.2 months. 10.3, 71.3,
and 18.4% of patients were classified into low, intermediate, and high-risk CNS
IPI groups, respectively. Only one of 136 patients developed CNS relapse,
corresponding to an incidence of 0.7% and an estimated 2-year CNS relapse rate of
0.9% for the entire R2CHOP cohort. The estimated 2-year CNS relapse rates for the
low, intermediate, and high-risk groups were 0, 0, and 5.0%, respectively.
Frontline therapy with R2CHOP in patients with DLBCL is associated with a lower
than-expected rate of CNS relapse.
PMID- 29946111
TI - An in vitro potency assay using nicotinic acetylcholine receptor binding works
well with antivenoms against Bungarus candidus and Naja naja.
AB - In order to facilitate/expedite the production of effective and affordable snake
antivenoms, a novel in vitro potency assay was previously developed. The assay is
based on an antiserum's ability to bind to postsynaptic neurotoxin (PSNT) and
thereby inhibit the PSNT binding to the nicotinic acetylcholine receptor (nAChR).
The assay was shown to work well with antiserum against Thai Naja kaouthia which
produces predominantly the lethal PSNTs. In this work, the assay is demonstrated
to work well with antiserum/antivenom against Bungarus candidus (BC), which also
produces lethal presynaptic neurotoxins, as well as antivenom against Sri Lankan
Naja naja (NN), which produces an abundance of cytotoxins. The in vitro and in
vivo median effective ratios (ER50s) for various batches of antisera against BC
showed a correlation (R2) of 0.8922 (p < 0.001) while the corresponding value for
the anti-NN antivenom was R2 = 0.7898 (p < 0.01). These results, together with
the known toxin profiles of various genera of elapids, suggest that this in vitro
assay could be used with antisera against other species of Bungarus and Naja and
possibly other neurotoxic snake venoms worldwide. The assay should significantly
save numerous lives of mice and accelerate production of life-saving antivenoms.
PMID- 29946108
TI - Sex differences in neural mechanisms mediating reward and addiction.
AB - There is increasing evidence in humans and laboratory animals for biologically
based sex differences in every phase of drug addiction: acute reinforcing
effects, transition from occasional to compulsive use, withdrawal-associated
negative affective states, craving, and relapse. There is also evidence that many
qualitative aspects of the addiction phases do not differ significantly between
males and females, but one sex may be more likely to exhibit a trait than the
other, resulting in population differences. The conceptual framework of this
review is to focus on hormonal, chromosomal, and epigenetic organizational and
contingent, sex-dependent mechanisms of four neural systems that are known
primarily in males-to be key players in addiction: dopamine, mu-opioid receptors
(MOR), kappa opioid receptors (KOR), and brain-derived neurotrophic factor
(BDNF). We highlight data demonstrating sex differences in development,
expression, and function of these neural systems as they relate-directly or
indirectly-to processes of reward and addictive behavior, with a focus on
psychostimulants and opioids. We identify gaps in knowledge about how these
neural systems interact with sex to influence addictive behavior, emphasizing
throughout that the impact of sex can be highly nuanced and male/female data
should be reported regardless of the outcome.
PMID- 29946112
TI - Antithrombotic therapy for venous thromboembolism in myeloproliferative
neoplasms.
AB - In myeloproliferative neoplasms (MPNs) the incidence of venous thromboembolism
(VTE) is 0.6-1.0 per 100 pt-years, and the rate of recurrence after VTE is 6.0
6.5 per 100 pt-yrs. Vitamin K-antagonists (VKA) reduces the risk of recurrence
after VTE at usual sites (i.e., deep venous thrombosis (DVT) of the legs and
pulmonary embolism (PE)) by 48-69%, with a rate of recurrent thrombosis per 100
pt-yrs of 3.4-4.7 on VKA and 8.9-9.6 off VKA; VKA discontinuation produces a 2.2
fold increased risk of novel thrombotic events with respect to continuation.
However, the rate of both recurrent thrombosis and major bleeding on VKA is
higher in MPN patients than in non-MPN patients, and the risk-benefit balance of
long-term VKA treatment is challenging. In the absence of strong evidence, the
tailored management of MPN-related VTE should operatively consider the risk
categories for recurrence and bleed well established in the non-MPN setting. In
summary, MPN patients with VTE are candidates for life-long VKA treatment,
especially after unprovoked proximal DVT and PE. Aspirin can offer a moderate
benefit in those patients who stop anticoagulation. The use of direct oral
anticoagulants should be explored aiming to ameliorate the rate of bleeding.
PMID- 29946114
TI - 2-carba cyclic phosphatidic acid suppresses inflammation via regulation of
microglial polarisation in the stab-wounded mouse cerebral cortex.
AB - Traumatic brain injury (TBI) is caused by physical damage to the brain and it
induces blood-brain barrier (BBB) breakdown and inflammation. To diminish the
sequelae of TBI, it is important to decrease haemorrhage and alleviate
inflammation. In this study, we aimed to determine the effects of 2-carba-cyclic
phosphatidic acid (2ccPA) on the repair mechanisms after a stab wound injury as a
murine TBI model. The administration of 2ccPA suppressed serum immunoglobulin
extravasation after the injury. To elucidate the effects of 2ccPA on inflammation
resulting from TBI, we analysed the mRNA expression of inflammatory cytokines. We
found that 2ccPA prevents a TBI-induced increase in the mRNA expression of Il
1beta, Il-6, Tnf-alpha and Tgf-beta1. In addition, 2ccPA reduces the elevation of
Iba1 levels. These data suggest that 2ccPA attenuates the inflammation after a
stab wound injury via the modulation of pro-inflammatory cytokines release from
microglial cells. Therefore, we focused on the function of 2ccPA in microglial
polarisation towards M1 or M2 phenotypes. The administration of 2ccPA decreased
the number of M1 and increased the number of M2 type microglial cells, indicating
that 2ccPA modulates the microglial polarisation and shifts them towards M2
phenotype. These data suggest that 2ccPA treatment suppresses the extent of BBB
breakdown and inflammation after TBI.
PMID- 29946115
TI - Red palm olein supplementation on cytokines, endothelial function and lipid
profile in centrally overweight individuals: a randomised controlled trial.
AB - BACKGROUND/OBJECTIVES: The consumption of antioxidant-rich cooking oil such as
red palm olein may be cardioprotective from the perspective of subclinical
inflammation and endothelial function. SUBJECTS/METHODS: Using a crossover
design, we conducted a randomised controlled trial in 53 free-living high-risk
abdominally overweight subjects, comparing the effects of incorporating red palm
olein (with palm olein as control) in a supervised isocaloric 2100 kcal diet of
30% en fat, two-thirds (45 g/day) of which were derived from the test oil for a
period of 6 weeks each. RESULTS: We did not observe a significant change in
interleukin-6 (IL-6), in parallel with other pro-inflammatory (tumour necrosis
factor-beta, interleukin-1beta, IL-1beta, high sensitivity C-reactive protein,
hsCRP) and endothelial function (soluble intercellular adhesion molecules, sICAM,
soluble intravascular adhesion molecules, sVCAM) parameters. Interestingly, we
observed a significant reduction in oxidised LDL levels (P < 0.0386) while on the
red palm olein diet, together with the increase in plasma alpha tocopherol (P <
0.0002), alpha carotene (P < 0.0001) and beta carotene (P < 0.0001)
concentrations compared with palm olein diet. CONCLUSION: Red palm olein did not
improve subclinical inflammation and endothelial function despite profound
increase in antioxidant levels. The positive improvement in oxidised LDL merits
further attention in this group of subjects at risk of developing cardiovascular
disease.
PMID- 29946113
TI - Granzyme B is elevated in autoimmune blistering diseases and cleaves key
anchoring proteins of the dermal-epidermal junction.
AB - In healthy skin, epidermis and dermis are anchored together at the dermal
epidermal junction (DEJ), a specialized basement membrane pivotal for skin
integrity and function. However, increased inflammation in the DEJ is associated
with the disruption and separation of this junction and sub-epidermal blistering.
Granzyme B (GzmB) is a serine protease secreted by immune cells. Dysregulated
inflammation may lead to increased GzmB accumulation and proteolysis in the
extracellular milieu. Although elevated GzmB is observed at the level of the DEJ
in inflammatory and blistering skin conditions, the present study is the first to
explore GzmB in the context of DEJ degradation in autoimmune sub-epidermal
blistering. In the present study, GzmB induced separation of the DEJ in healthy
human skin. Subsequently, alpha6/beta4 integrin, collagen VII, and collagen XVII
were identified as extracellular substrates for GzmB through western blot, and
specific cleavage sites were identified by mass spectrometry. In human bullous
pemphigoid, dermatitis herpetiformis, and epidermolysis bullosa acquisita, GzmB
was elevated at the DEJ when compared to healthy samples, while alpha6/beta4
integrin, collagen VII, and collagen XVII were reduced or absent in the area of
blistering. In summary, our results suggest that regardless of the initial
causation of sub-epidermal blistering, GzmB activity is a common final pathway
that could be amenable to a single targeted treatment approach.
PMID- 29946116
TI - Incorrect analyses were used in "Different enteral nutrition formulas have no
effect on glucose homeostasis but on diet-induced thermogenesis in critically ill
medical patients: a randomized controlled trial" and corrected analyses are
requested.
PMID- 29946117
TI - Severity of Airflow Obstruction and Work Loss in a Nationwide Population of
Working Age.
AB - The impact of COPD severity on labor force participation and work loss is not
well known. This study aimed to describe the characteristics of occupations and
to evaluate the reason for work loss based on the severity of airflow obstruction
(AO). We performed a cross-sectional study using data from the Korean National
Health and Nutrition Examination Survey V-VI. We identified 9,901 people aged 40
to 60 years who had normal or AO in spirometry test results. AO was defined as a
pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity
<70%. AO was present in 7.6% of the subjects, and 81.5%, 82.9%, and 71.6% of
subjects with mild, moderate, and severe-to-very severe AO were in the labor
force, respectively. Multivariable analyses revealed that severe-to-very severe
AO subjects were more likely to have precarious job (adjusted OR = 4.71, 95% CI =
1.70-13.06) and cite health-related problem as the reason for not being in the
labor force (adjusted OR = 3.38, 95% CI = 1.03-11.02). Overall, AO was not
associated with any significant changes in labor force participation. However,
subjects with severe-to-very severe disease were more likely to drop out of the
labor force owing to their health-related problems.
PMID- 29946119
TI - Optimization of Optomotor Response-based Visual Function Assessment in Mice.
AB - Optomotor response/reflex (OMR) assays are emerging as a powerful and versatile
tool for phenotypic study and new drug discovery for eye and brain disorders. Yet
efficient OMR assessment for visual performance in mice remains a challenge.
Existing OMR testing devices for mice require a lengthy procedure and may be
subject to bias due to use of artificial criteria. We developed an optimized
staircase protocol that utilizes mouse head pausing behavior as a novel indicator
for the absence of OMR, to allow rapid and unambiguous vision assessment. It
provided a highly sensitive and reliable method that can be easily implemented
into automated or manual OMR systems to allow quick and unbiased assessment for
visual acuity and contrast sensitivity in mice. The sensitivity and quantitative
capacity of the protocol were validated using wild type mice and an inherited
mouse model of retinal degeneration - mice carrying rhodopsin deficiency and
exhibiting progressive loss of photoreceptors. Our OMR system with this protocol
was capable of detecting progressive visual function decline that was closely
correlated with the loss of photoreceptors in rhodopsin deficient mice. It
provides significant advances over the existing methods in the currently
available OMR devices in terms of sensitivity, accuracy and efficiency.
PMID- 29946118
TI - Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a
processing by hnRNP A1.
AB - Post-transcriptional mechanisms play a predominant role in the control of
microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs
by RNA-binding proteins (RBPs) influences their processing; however, the
mechanistic basis for how levels of individual or subsets of miRNAs are regulated
is mostly unexplored. We previously showed that hnRNP A1, an RBP implicated in
many aspects of RNA processing, acts as an auxiliary factor that promotes the
Microprocessor-mediated processing of pri-mir-18a. Here, by using an integrative
structural biology approach, we show that hnRNP A1 forms a 1:1 complex with pri
mir-18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence
motifs in the terminal loop of pri-mir-18a. Terminal loop binding induces an
allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes
its downstream processing. Our results highlight terminal loop RNA recognition by
RBPs as a potential general principle of miRNA biogenesis and regulation.
PMID- 29946121
TI - An aquatic origin of retroviruses.
PMID- 29946120
TI - Manipulation of visible-light polarization with dendritic cell-cluster
metasurfaces.
AB - Cross-polarization conversion plays an important role in visible light
manipulation. Metasurface with asymmetric structure can be used to achieve
polarization conversion of linearly polarized light. Based on this, we design a
quasi-periodic dendritic metasurface model composed of asymmetric dendritic
cells. The simulation indicates that the asymmetric dendritic structure can
vertically rotate the polarization direction of the linear polarization wave in
visible light. Silver dendritic cell-cluster metasurface samples were prepared by
the bottom-up electrochemical deposition. It experimentally proved that they
could realize the cross - polarization conversion in visible light. Cross
polarized propagating light is deflected into anomalous refraction channels.
Dendritic cell-cluster metasurface with asymmetric quasi-periodic structure
conveys significance in cross-polarization conversion research and features
extensive practical application prospect and development potential.
PMID- 29946122
TI - Falling into your own trap.
PMID- 29946123
TI - Gut microbiota bile acid metabolism controls cancer immunosurveillance.
PMID- 29946124
TI - Cyanobacterial blooms.
AB - Cyanobacteria can form dense and sometimes toxic blooms in freshwater and marine
environments, which threaten ecosystem functioning and degrade water quality for
recreation, drinking water, fisheries and human health. Here, we review evidence
indicating that cyanobacterial blooms are increasing in frequency, magnitude and
duration globally. We highlight species traits and environmental conditions that
enable cyanobacteria to thrive and explain why eutrophication and climate change
catalyse the global expansion of cyanobacterial blooms. Finally, we discuss
management strategies, including nutrient load reductions, changes in
hydrodynamics and chemical and biological controls, that can help to prevent or
mitigate the proliferation of cyanobacterial blooms.
PMID- 29946125
TI - Revealing the immune perturbation of black phosphorus nanomaterials to
macrophages by understanding the protein corona.
AB - The increasing number of biological applications for black phosphorus (BP)
nanomaterials has precipitated considerable concern about their interactions with
physiological systems. Here we demonstrate the adsorption of plasma protein onto
BP nanomaterials and the subsequent immune perturbation effect on macrophages.
Using liquid chromatography tandem mass spectrometry, 75.8% of the proteins bound
to BP quantum dots were immune relevant proteins, while that percentage for BP
nanosheet-corona complexes is 69.9%. In particular, the protein corona
dramatically reshapes BP nanomaterial-corona complexes, influenced cellular
uptake, activated the NF-kappaB pathway and even increased cytokine secretion by
2-4-fold. BP nanomaterials induce immunotoxicity and immune perturbation in
macrophages in the presence of a plasma corona. These findings offer important
insights into the development of safe and effective BP nanomaterial-based
therapies.
PMID- 29946127
TI - Technology in the management of type 1 diabetes mellitus - current status and
future prospects.
AB - Type 1 diabetes mellitus (T1DM) represents 5-10% of diabetes cases worldwide. The
incidence of T1DM is increasing, and there is no immediate prospect of a cure. As
such, lifelong management is required, the burden of which is being eased by
novel treatment modalities, particularly from the field of diabetes technologies.
Continuous glucose monitoring has become the standard of care and includes
factory-calibrated subcutaneous glucose monitoring and long-term implantable
glucose sensing. In addition, considerable progress has been made in technology
enabled glucose-responsive insulin delivery. The first hybrid insulin-only closed
loop system has been commercialized, and other closed-loop systems are under
development, including dual-hormone glucose control systems. This Review focuses
on well-established diabetes technologies, including glucose sensing, pen-based
insulin delivery, data management and data analytics. We also cover insulin pump
therapy, threshold-based suspend, predictive low-glucose suspend and single
hormone and dual-hormone closed-loop systems. Clinical practice recommendations
for insulin pump therapy and continuous glucose monitoring are presented, and
ongoing research and future prospects are highlighted. We conclude that the
management of T1DM is improved by diabetes technology for the benefit of the
majority of people with T1DM, their caregivers and guardians and health-care
professionals treating patients with T1DM.
PMID- 29946126
TI - Viscoelastic properties of Pseudomonas aeruginosa variant biofilms.
AB - Pseudomonas aeruginosa evolves during chronic pulmonary infections of cystic
fibrosis (CF) patients, forming pathoadapted variants that are persistent. Mucoid
and rugose small-colony variants (RSCVs) are typically isolated from sputum of CF
patients. These variants overproduce exopolysaccharides in the biofilm
extracellular polymeric substance (EPS). Currently, changes to the biophysical
properties of RSCV and mucoid biofilms due to variations in EPS are not well
understood. This knowledge may reveal how lung infections resist host clearance
mechanisms. Here, we used mechanical indentation and shear rheometry to analyse
the viscoelasticity of RSCV and mucoid colony-biofilms compared to their isogenic
parent at 2-, 4-, and 6-d. While the viscoelasticity of parental colony-biofilms
underwent fluctuating temporal changes, in contrast, RSCV and mucoid colony
biofilms showed a gradual progression to more elastic-solid behaviour.
Theoretical indices of mucociliary and cough clearance predict that mature 6-d
parental and RSCV biofilms may show reduced cough clearance from the lung, while
early mucoid biofilms may show reduced clearance by both mechanisms. We propose
that viscoelasticity be considered a virulence property of biofilms.
PMID- 29946128
TI - Follistatin inactivation improves glucose tolerance.
PMID- 29946129
TI - Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic
plaque inflammation by positron emission tomography.
AB - Inflammation plays an important role in the development of atherosclerosis and
its complications. Because the folate receptor beta (FR-beta) is selectively
expressed on macrophages, an FR targeted imaging agent could be useful for
assessment of atherosclerotic inflammation. We investigated aluminum fluoride-18
labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate (18F-FOL)
for the detection of atherosclerotic plaque inflammation. We studied
atherosclerotic plaques in mice, rabbits, and human tissue samples using 18F-FOL
positron emission tomography/computed tomography (PET/CT). Compound 2-deoxy-2
[18F]fluoro-D-glucose (18F-FDG) was used as a comparison. Firstly, we found that
the in vitro binding of 18F-FOL co-localized with FR-beta-positive macrophages in
carotid endarterectomy samples from patients with recent ischemic symptoms. We
then demonstrated specific accumulation of intravenously administered 18F-FOL in
atherosclerotic plaques in mice and rabbits using PET/CT. We noticed that the 18F
FOL uptake correlated with the density of macrophages in plaques and provided a
target-to-background ratio as high as 18F-FDG, but with considerably lower
myocardial uptake. Thus, 18F-FOL PET/CT targeting of FR-beta-positive macrophages
presents a promising new tool for the in vivo imaging of atherosclerotic
inflammation.
PMID- 29946130
TI - Pooled CRISPR interference screening enables genome-scale functional genomics
study in bacteria with superior performance.
AB - To fully exploit the microbial genome resources, a high-throughput experimental
platform is needed to associate genes with phenotypes at the genome level. We
present here a novel method that enables investigation of the cellular
consequences of repressing individual transcripts based on the CRISPR
interference (CRISPRi) pooled screening in bacteria. We identify rules for guide
RNA library design to handle the unique structure of prokaryotic genomes by
tiling screening and construct an E. coli genome-scale guide RNA library (~60,000
members) accordingly. We show that CRISPRi outperforms transposon sequencing, the
benchmark method in the microbial functional genomics field, when similar library
sizes are used or gene length is short. This tool is also effective for mapping
phenotypes to non-coding RNAs (ncRNAs), as elucidated by a comprehensive tRNA
fitness map constructed here. Our results establish CRISPRi pooled screening as a
powerful tool for mapping complex prokaryotic genetic networks in a precise and
high-throughput manner.
PMID- 29946131
TI - S-nitrosation of protein phosphatase 1 mediates alcohol-induced ciliary
dysfunction.
AB - Alcohol use disorder (AUD) is a strong risk factor for development and mortality
of pneumonia. Mucociliary clearance, a key innate defense against pneumonia, is
perturbed by alcohol use. Specifically, ciliated airway cells lose the ability to
increase ciliary beat frequency (CBF) to beta-agonist stimulation after prolonged
alcohol exposure. We previously found that alcohol activates protein phosphatase
1 (PP1) through a redox mechanism to cause ciliary dysfunction. Therefore, we
hypothesized that PP1 activity is enhanced by alcohol exposure through an S
nitrosothiol-dependent mechanism resulting in desensitization of CBF stimulation.
Bronchoalveolar S-nitrosothiol (SNO) content and tracheal PP1 activity was
increased in wild-type (WT) mice drinking alcohol for 6-weeks compared to control
mice. In contrast, alcohol drinking did not increase SNO content or PP1 activity
in nitric oxide synthase 3-deficient mice. S-nitrosoglutathione induced PP1
dependent CBF desensitization in mouse tracheal rings, cultured cells and
isolated cilia. In vitro expression of mutant PP1 (cysteine 155 to alanine) in
primary human airway epithelial cells prevented CBF desensitization after
prolonged alcohol exposure compared to cells expressing WT PP1. Thus, redox
modulation in the airways by alcohol is an important ciliary regulatory
mechanism. Pharmacologic strategies to reduce S-nitrosation may enhance
mucociliary clearance and reduce pneumonia prevalence, mortality and morbidity
with AUD.
PMID- 29946132
TI - A new technique for nanoparticle transport and its application in a novel nano
sieve.
AB - A new technique is proposed to transport and further classify nanoparticles of
different sizes. A graphene sheet is used as the substrate; a nanoparticle is
placed on the substrate and a sliding block is located below the substrate. As
the sliding block moves under the graphene substrate, a driving force is yielded
from the van der Waals interaction between the sliding block and the
nanoparticle. The effects of the pre-tension of the graphene substrate, size and
number of layers of the nanoparticle, slip velocity, the interface
commensurability and temperature on nanoparticle transportation are
systematically investigated. It is found that a pre-tensioned graphene substrate
could provide easier nanoparticle transport. The initial movement of the
nanoparticle depends on the competition between the in-plane force and the
driving force, while the subsequent transport depends on the slip velocity of the
sliding block and the viscous damping force. Based on such a new transport
mechanism, a novel nano-sieve can be designed, with which nanoparticles of
different sizes can be screened and classified spontaneously. Our findings may be
useful for promising designs of transportation, manipulation and classification
of nanoparticles.
PMID- 29946133
TI - Phenotypic characterization of murine models of cerebral cavernous malformations.
AB - Cerebral cavernous malformations (CCMs) are clusters of dilated capillaries that
affect around 0.5% of the population. CCMs exist in two forms, sporadic and
familial. Mutations in three documented genes, KRIT1(CCM1), CCM2, and
PDCD10(CCM3), cause the autosomal dominant form of the disease, and somatic
mutations in these same genes underlie lesion development in the brain. Murine
models with constitutive or induced loss of respective genes have been applied to
study disease pathobiology and therapeutic manipulations. We aimed to analyze the
phenotypic characteristic of two main groups of models, the chronic heterozygous
models with sensitizers promoting genetic instability, and the acute neonatal
induced homozygous knockout model. Acute model mice harbored a higher lesion
burden than chronic models, more localized in the hindbrain, and largely lacking
iron deposition and inflammatory cell infiltrate. The chronic model mice showed a
lower lesion burden localized throughout the brain, with significantly greater
perilesional iron deposition, immune B- and T-cell infiltration, and less
frequent junctional protein immunopositive endothelial cells. Lesional
endothelial cells in both models expressed similar phosphorylated myosin light
chain immunopositivity indicating Rho-associated protein kinase activity. These
data suggest that acute models are better suited to study the initial formation
of the lesion, while the chronic models better reflect lesion maturation,
hemorrhage, and inflammatory response, relevant pathobiologic features of the
human disease.
PMID- 29946134
TI - An in vivo model for thyroid regeneration and folliculogenesis.
AB - While thyroid is considered to be a dormant organ, when required, it can
regenerate through increased cell proliferation. However, the mechanism for
regeneration remains unknown. Nkx2-1(fl/fl);TPO-cre mouse thyroids exhibit a very
disorganized appearance because their thyroids continuously degenerate and
regenerate. In mouse thyroids, a cluster of cells are found near the tracheal
cartilage and muscle, which are positive for expression of NKX2-1, the master
transcription factor governing thyroid development and function. In the present
study, we propose that this cluster of NKX2-1-positive cells may be the precursor
cells that mature to become thyroid follicular cells, forming thyroid follicles.
We also found that phosphorylation of AKT is induced by NKX2-1 in the proposed
thyroid progenitor-like side-population cell-derived thyroid cell line (SPTL)
cells, suggesting the possibility that NKX2-1 plays a role in differentiation
through the modulation of AKT signaling. This study revealed that Nkx2
1(fl/fl);TPO-cre mice provide a suitable model to study in vivo regeneration and
folliculogenesis of the thyroid.
PMID- 29946136
TI - Synthesis of Pure Enantiomers of Titanium(IV) Complexes with Chiral
Diaminobis(phenolato) Ligands and Their Biological Reactivity.
AB - Racemic and enantiomerically pure titanium(IV) complexes with ortho-brominated or
para-nitrated chiral diaminobis(phenolato) ligands were prepared with NH and NMe
cyclohexyldiamino bridges through ligand to metal chiral induction. The
hydrolytic behavior of the complexes was evaluated, identifying the N-methylated
complex as the most stable. A representative NH complex hydrolyzed to first give
a dimeric structure in solution as deduced by NMR diffusion measurements,
followed by formation of clusters with higher nuclearity, as was supported by X
ray characterization of a tetranuclear cluster obtained in trace amounts
following 30 days in water solutions. The cytotoxicity of the enantiomerically
pure and racemic complexes was measured on HT-29 human colon cancer cell line
based on the MTT assay; all stereochemical configurations of the N-methylated
complex were inactive, whereas for the NH complexes, the racemic mixtures were
mostly inactive but the pure enantiomers exhibited similarly high cytotoxicity,
supporting a polynuclear active species. Analysis of the two enantiomers of the
most active brominated complex for their cytotoxicity on human ovarian A2780,
cisplatin resistant A2780cp and multi-drug-resistant A2780adr cell lines as well
as for their apoptosis induction on the A2780 line revealed similar reactivity,
supporting a similar mechanism for the two enantiomers.
PMID- 29946137
TI - Neuroprotective effects of Magnoliae Flos extract in mouse hippocampal neuronal
cells.
AB - Magnoliae Flos (MF) is a traditional medicinal herb used for managing rhinitis,
sinusitis and headache. The purpose of the present study was to determine the
neuroprotective effect of MF against glutamate-induced oxidative stress and to
assess the underlying mechanism. Glutamate is a major endogenous excitatory
neurotransmitter in the brain and contributes to the development of
neurodegenerative diseases by excessive activation. MF extract was subjected to a
neuroprotective effect assay in HT22 mouse hippocampal cells. The mechanism
underlying the neuroprotective effect of MF extract was evaluated by assaying
reactive oxygen species (ROS) levels, intracellular Ca2+ levels, mitochondrial
membrane potential, glutathione level and antioxidant enzyme activity in HT22
cells. MF extract significantly decreased glutamate-induced death of HT22 cells
(80.83 +/- 7.34% relative neuroprotection). MF extract reduced the intracellular
ROS and Ca2+ levels and increased the glutathione level and glutathione reductase
and glutathione peroxide activities. Moreover, MF extract attenuated the
mitochondrial membrane potential in HT22 cells. These results suggested that MF
extract exerts a neuroprotective effect against oxidative stress HT22 cells,
which was mediated by its antioxidant activity.
PMID- 29946135
TI - Eukaryotic core promoters and the functional basis of transcription initiation.
AB - RNA polymerase II (Pol II) core promoters are specialized DNA sequences at
transcription start sites of protein-coding and non-coding genes that support the
assembly of the transcription machinery and transcription initiation. They enable
the highly regulated transcription of genes by selectively integrating regulatory
cues from distal enhancers and their associated regulatory proteins. In this
Review, we discuss the defining properties of gene core promoters, including
their sequence features, chromatin architecture and transcription initiation
patterns. We provide an overview of molecular mechanisms underlying the function
and regulation of core promoters and their emerging functional diversity, which
defines distinct transcription programmes. On the basis of the established
properties of gene core promoters, we discuss transcription start sites within
enhancers and integrate recent results obtained from dedicated functional assays
to propose a functional model of transcription initiation. This model can explain
the nature and function of transcription initiation at gene starts and at
enhancers and can explain the different roles of core promoters, of Pol II and
its associated factors and of the activating cues provided by enhancers and the
transcription factors and cofactors they recruit.
PMID- 29946138
TI - Comparative genomics of Campylobacter concisus: Analysis of clinical strains
reveals genome diversity and pathogenic potential.
AB - In recent years, an increasing number of Campylobacter species have been
associated with human gastrointestinal (GI) diseases including gastroenteritis,
inflammatory bowel disease, and colorectal cancer. Campylobacter concisus, an
oral commensal historically linked to gingivitis and periodontitis, has been
increasingly detected in the lower GI tract. In the present study, we generated
robust genome sequence data from C. concisus strains and undertook a
comprehensive pangenome assessment to identify C. concisus virulence properties
and to explain potential adaptations acquired while residing in specific
ecological niche(s) of the GI tract. Genomes of 53 new C. concisus strains were
sequenced, assembled, and annotated including 36 strains from gastroenteritis
patients, 13 strains from Crohn's disease patients and four strains from colitis
patients (three collagenous colitis and one lymphocytic colitis). When compared
with previous published sequences, strains clustered into two main
groups/genomospecies (GS) with phylogenetic clustering explained neither by
disease phenotype nor sample location. Paired oral/faecal isolates, from the same
patient, indicated that there are few genetic differences between oral and gut
isolates which suggests that gut isolates most likely reflect oral strain
relocation. Type IV and VI secretion systems genes, genes known to be important
for pathogenicity in the Campylobacter genus, were present in the genomes
assemblies, with 82% containing Type VI secretion system genes. Our findings
indicate that C. concisus strains are genetically diverse, and the variability in
bacterial secretion system content may play an important role in their virulence
potential.
PMID- 29946140
TI - FGFR1 reprogrammes cell metabolism.
PMID- 29946139
TI - Linking minimum inhibitory concentrations to whole genome sequence-predicted drug
resistance in Mycobacterium tuberculosis strains from Romania.
AB - Mycobacterium tuberculosis drug resistance poses a major threat to tuberculosis
control. Current phenotypic tests for drug susceptibility are time-consuming,
technically complex, and expensive. Whole genome sequencing is a promising
alternative, though the impact of different drug resistance mutations on the
minimum inhibitory concentration (MIC) remains to be investigated. We examined
the genomes of 72 phenotypically drug-resistant Mycobacterium tuberculosis
isolates from 72 Romanian patients for drug resistance mutations. MICs for first-
and second-line drugs were determined using the MycoTB microdilution method.
These MICs were compared to macrodilution critical concentration testing by the
Mycobacterium Growth Indicator Tube (MGIT) platform and correlated to drug
resistance mutations. Sixty-three (87.5%) isolates harboured drug resistance
mutations; 48 (66.7%) were genotypically multidrug-resistant. Different drug
resistance mutations were associated with different MIC ranges; katG S315T for
isoniazid, and rpoB S450L for rifampicin were associated with high MICs. However,
several mutations such as in rpoB, rrs and rpsL, or embB were associated with MIC
ranges including the critical concentration for rifampicin, aminoglycosides or
ethambutol, respectively. Different resistance mutations lead to distinct MICs,
some of which may still be overcome by increased dosing. Whole genome sequencing
can aid in the timely diagnosis of Mycobacterium tuberculosis drug resistance and
guide clinical decision-making.
PMID- 29946141
TI - The emerging novel avian leukosis virus with mutations in the pol gene shows
competitive replication advantages both in vivo and in vitro.
AB - The avian leukosis virus subgroup K (ALV-K), a novel subgroup in Chinese
indigenous chicken breeds, has been difficult to isolate in the past due to its
poor replication ability. However, according to the latest monitoring data, the
replication ability and isolation rate of ALV-K have clearly increased, and new
strains with mutations in the pol gene have also been found. To determine the
effects of such mutations on the biological characteristics of ALV-K, a pair of
infectious clones were constructed and rescued. The first virus was an ALV-K
Chinese isolate with mutations in its pol gene, named rSDAUAK-11. The second
virus was a recuperative rSDAUAK-11 from which mutations in the pol gene were
recovered according to the corresponding region of the ALV-K prototype virus
JS11C1, named rRSDAUAK-11. In addition, two quantitative real-time polymerase
chain reaction assays were developed to specifically detect these virus strains.
Using such methods, we observed a marked improvement of the reverse transcriptase
activity, replication ability and vertical transmission ability of rSDAUAK-11,
which also revealed a formidable competitive advantage in mixed infection with
rRSDAUAK-11 and corresponded to the differences between the wild strains SDAUAK
11 and JS11C1. Accordingly, our findings not only show that mutations in the pol
gene are an important molecular mechanism contributing to corresponding changes
in the biological characteristics of the newest ALV-K but also emphasize the
potential future eradication of ALV.
PMID- 29946142
TI - Genome-wide bisulphite-sequencing reveals organ-specific methylation patterns in
chickpea.
AB - DNA methylation is widely known to regulate gene expression in eukaryotes. Here,
we unraveled DNA methylation patterns in cultivated chickpea to understand the
regulation of gene expression in different organs. We analyzed the methylation
pattern in leaf tissue of wild chickpea too, and compared it with cultivated
chickpea. Our analysis indicated abundant CG methylation within gene-body and CHH
methylation in intergenic regions of the chickpea genome in all the organs
examined. Analysis of differentially methylated regions (DMRs) demonstrated a
higher number of CG context DMRs in wild chickpea and CHH context DMRs in
cultivated chickpea. We observed increased preponderance of hypermethylated DMRs
in the promoter regions and hypomethylated DMRs in the genic regions in
cultivated chickpea. Genomic location and context of the DMRs correlated well
with expression of proximal genes. Our results put forth a positive correlation
of promoter hypermethylation with increased transcript abundance via
identification of DMR-associated genes involved in flower development in
cultivated chickpea. The atypical correlation observed between promoter
hypermethylation and increased transcript abundance might be dependent on 24-nt
small RNAs and transcription factors binding to the promoter region. This study
provides novel insights into DNA methylation patterns in chickpea and their role
in regulation of gene expression.
PMID- 29946144
TI - Dissecting the mammary gland one cell at a time.
AB - Dissecting cellular differentiation hierarchies in the mammary gland is a
prerequisite for understanding both normal development and malignant
transformation during tumorigenesis and tumor cell-of-origin. To achieve these
goals, several recent papers utilized single cell RNA-seq and lineage tracing to
improve our understanding of the composition of the mammary epithelium at
different developmental stages.
PMID- 29946145
TI - Cerebral photoreception in mantis shrimp.
AB - The currently unsurpassed diversity of photoreceptors found in the eyes of
stomatopods, or mantis shrimps, is achieved through a variety of opsin-based
visual pigments and optical filters. However, the presence of extraocular
photoreceptors in these crustaceans is undescribed. Opsins have been found in
extraocular tissues across animal taxa, but their functions are often unknown.
Here, we show that the mantis shrimp Neogonodactylus oerstedii has functional
cerebral photoreceptors, which expands the suite of mechanisms by which mantis
shrimp sense light. Illumination of extraocular photoreceptors elicits behaviors
akin to common arthropod escape responses, which persist in blinded individuals.
The anterior central nervous system, which is illuminated when a mantis shrimp's
cephalothorax protrudes from its burrow to search for predators, prey, or mates,
appears to be photosensitive and to feature two types of opsin-based, potentially
histaminergic photoreceptors. A pigmented ventral eye that may be capable of
color discrimination extends from the cerebral ganglion, or brain, against the
transparent outer carapace, and exhibits a rapid electrical response when
illuminated. Additionally, opsins and histamine are expressed in several
locations of the eyestalks and cerebral ganglion, where any photoresponses could
contribute to shelter-seeking behaviors and other functions.
PMID- 29946143
TI - In utero nanoparticle delivery for site-specific genome editing.
AB - Genetic diseases can be diagnosed early during pregnancy, but many monogenic
disorders continue to cause considerable neonatal and pediatric morbidity and
mortality. Early intervention through intrauterine gene editing, however, could
correct the genetic defect, potentially allowing for normal organ development,
functional disease improvement, or cure. Here we demonstrate safe intravenous and
intra-amniotic administration of polymeric nanoparticles to fetal mouse tissues
at selected gestational ages with no effect on survival or postnatal growth. In
utero introduction of nanoparticles containing peptide nucleic acids (PNAs) and
donor DNAs corrects a disease-causing mutation in the beta-globin gene in a mouse
model of human beta-thalassemia, yielding sustained postnatal elevation of blood
hemoglobin levels into the normal range, reduced reticulocyte counts, reversal of
splenomegaly, and improved survival, with no detected off-target mutations in
partially homologous loci. This work may provide the basis for a safe and
versatile method of fetal gene editing for human monogenic disorders.
PMID- 29946146
TI - Double Strand Break DNA Repair occurs via Non-Homologous End-Joining in Mouse MII
Oocytes.
AB - The unique biology of the oocyte means that accepted paradigms for DNA repair and
protection are not of direct relevance to the female gamete. Instead,
preservation of the integrity of the maternal genome depends on endogenous
protein stores and/or mRNA transcripts accumulated during oogenesis. The aim of
this study was to determine whether mature (MII) oocytes have the capacity to
detect DNA damage and subsequently mount effective repair. For this purpose, DNA
double strand breaks (DSB) were elicited using the topoisomerase II inhibitor,
etoposide (ETP). ETP challenge led to a rapid and significant increase in DSB (P
= 0.0002) and the consequential incidence of metaphase plate abnormalities (P =
0.0031). Despite this, ETP-treated MII oocytes retained their ability to
participate in in vitro fertilisation, though displayed reduced developmental
competence beyond the 2-cell stage (P = 0.02). To account for these findings, we
analysed the efficacy of DSB resolution, revealing a significant reduction in DSB
lesions 4 h post-ETP treatment. Notably, this response was completely abrogated
by pharmacological inhibition of key elements (DNA-PKcs and DNA ligase IV) of the
canonical non-homologous end joining DNA repair pathway, thus providing the first
evidence implicating this reparative cascade in the protection of the maternal
genome.
PMID- 29946147
TI - Author Correction: Hexokinase-2 depletion inhibits glycolysis and induces
oxidative phosphorylation in hepatocellular carcinoma and sensitizes to
metformin.
AB - In the originally published version of this Article, the colours of the bars in
Fig. 4b were inadvertently switched during the production process, such that 'HK2
Dox' and 'HK2+Dox' were depicted in red and 'Nt-Dox' and 'Nt+Dox' were depicted
in blue. These errors have now been corrected in both the PDF and HTML versions
of the Article.
PMID- 29946149
TI - Influence of the viscosity of healthy and diseased human mucins on the motility
of Helicobacter pylori.
AB - We present particle tracking microrheology results on human mucins, isolated from
normal surface and gland mucosa and one tumor sample, and examine the motility of
Helicobacter pylori in these mucins. At 1.5% concentration human mucin solutions
are purely viscous, with viscosity eta (gland mucin) > eta (surface mucin) > eta
(tumor mucin). In the presence of motile H. pylori bacteria, particle diffusion
is enhanced, with diffusivity D+bac(tumor mucin) > D+bac(gland mucin) >
D+bac(surface mucin). The surface and tumor mucin solutions exhibit an elastic
response in the presence of bacteria. Taken together these results imply that
particle diffusion and active swimming are coupled and impact the rheology of
mucin solutions. Both J99 wild type (WT) and its isogenic DeltababA/DeltasabA
mutant swam well in broth or PGM solutions. However, the human mucins affected
their motility differently, rendering them immotile in certain instances. The
distribution of swimming speeds in human mucin solutions was broader with a large
fraction of fast swimmers compared to PGM and broth. The bacteria swam fastest in
the tumor mucin solution correlating with it having the lowest viscosity of all
mucin solutions. Overall, these results suggest that mucins from different tissue
locations and disease status differ in their microrheological properties and
their effect on H. pylori motility.
PMID- 29946148
TI - Metformin add-on continuous subcutaneous insulin infusion on precise insulin
doses in patients with type 2 diabetes.
AB - To investigate whether metformin add-on to the continuous subcutaneous insulin
infusion (Met + CSII) therapy leads to a significant reduction in insulin doses
required by type 2 diabetes (T2D) patients to maintain glycemic control, and an
improvement in glycemic variation (GV) compared to CSII only therapy. We analyzed
data from our two randomized, controlled open-label trials. Newly diagnoses T2D
patients were randomized assigned to receive either CSII therapy or Met + CSII
therapy for 4 weeks. Subjects were subjected to a 4-day continuous glucose
monitoring (CGM) at the endpoint. Insulin doses and GV profiles were analyzed.
The primary endpoint was differences in insulin doses and GV between the two
groups. A total of 188 subjects were admitted as inpatients. Subjects in
metformin add-on therapy required significantly lower total, basal and bolus
insulin doses than those of control group. CGM data showed that patients in Met +
CSII group exhibited significant reduction in the 24-hr mean amplitude of
glycemic excursions (MAGE), the standard deviation, and the coefficient of
variation compared to those of control group. Our data suggest that metformin add
on to CSII therapy leads to a significant reduction in insulin doses required by
T2D patients to control glycemic variations.
PMID- 29946150
TI - Activation of the p53-MDM4 regulatory axis defines the anti-tumour response to
PRMT5 inhibition through its role in regulating cellular splicing.
AB - Evasion of the potent tumour suppressor activity of p53 is one of the hurdles
that must be overcome for cancer cells to escape normal regulation of cellular
proliferation and survival. In addition to frequent loss of function mutations,
p53 wild-type activity can also be suppressed post-translationally through
several mechanisms, including the activity of PRMT5. Here we describe broad anti
proliferative activity of potent, selective, reversible inhibitors of protein
arginine methyltransferase 5 (PRMT5) including GSK3326595 in human cancer cell
lines representing both hematologic and solid malignancies. Interestingly, PRMT5
inhibition activates the p53 pathway via the induction of alternative splicing of
MDM4. The MDM4 isoform switch and subsequent p53 activation are critical
determinants of the response to PRMT5 inhibition suggesting that the integrity of
the p53-MDM4 regulatory axis defines a subset of patients that could benefit from
treatment with GSK3326595.
PMID- 29946151
TI - Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation
during pregnancy and after myocardial infarction.
AB - Cardiomyocyte proliferation stops at birth when the heart is no longer exposed to
maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to
promote maternal tolerance towards the fetus. Here, we report a role of Tregs in
promoting cardiomyocyte proliferation. Treg-conditioned medium promotes
cardiomyocyte proliferation, similar to the serum from pregnant animals.
Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and
Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte
proliferation. Treg depletion after myocardial infarction results in depressed
cardiac function, massive inflammation, and scarce collagen deposition. In
contrast, Treg injection reduces infarct size, preserves contractility, and
increases the number of proliferating cardiomyocytes. The overexpression of six
factors secreted by Tregs (Cst7, Tnfsf11, Il33, Fgl2, Matn2, and Igf2) reproduces
the therapeutic effect. In conclusion, Tregs promote fetal and maternal
cardiomyocyte proliferation in a paracrine manner and improve the outcome of
myocardial infarction.
PMID- 29946152
TI - The atypical subunit composition of respiratory complexes I and IV is associated
with original extra structural domains in Euglena gracilis.
AB - In mitochondrial oxidative phosphorylation, electron transfer from NADH or
succinate to oxygen by a series of large protein complexes in the inner
mitochondrial membrane (complexes I-IV) is coupled to the generation of an
electrochemical proton gradient, the energy of which is utilized by complex V to
generate ATP. In Euglena gracilis, a non-parasitic secondary green alga related
to trypanosomes, these respiratory complexes totalize more than 40 Euglenozoa
specific subunits along with about 50 classical subunits described in other
eukaryotes. In the present study the Euglena proton-pumping complexes I, III, and
IV were purified from isolated mitochondria by a two-steps liquid chromatography
approach. Their atypical subunit composition was further resolved and confirmed
using a three-steps PAGE analysis coupled to mass spectrometry identification of
peptides. The purified complexes were also observed by electron microscopy
followed by single-particle analysis. Even if the overall structures of the three
oxidases are similar to the structure of canonical enzymes (e.g. from mammals),
additional atypical domains were observed in complexes I and IV: an extra domain
located at the tip of the peripheral arm of complex I and a "helmet-like" domain
on the top of the cytochrome c binding region in complex IV.
PMID- 29946153
TI - Selection of validated hypervariable regions is crucial in 16S-based microbiota
studies of the female genital tract.
AB - Next-generation sequencing-based methods are extensively applied in studies of
the human microbiota using partial 16 S rRNA gene amplicons. However, they carry
drawbacks that are critical to consider when interpreting results, including
differences in outcome based on the hypervariable region(s) used. Here, we show
that primers spanning the V3/V4 region identify a greater number of taxa in the
vaginal microbiota than those spanning the V1/V2 region. In particular, taxa such
as Gardnerella vaginalis, Bifidobacterium bifidum and Chlamydia trachomatis, all
species that influence vaginal health and disease, are not represented in V1/V2
based community profiles. Accordingly, missing or underestimating the frequency
of these species overestimates the abundance of other taxa and fails to correctly
assess the bacterial diversity in the urogenital tract. We elaborate that
covering these taxa using the V3/V4 region leads to profound changes in the
assignment of community state types. Altogether, we show that the choice of
primers used for studying the vaginal microbiota has deep implications on the
biological evaluation of the results.
PMID- 29946154
TI - Splanchnic vein thrombosis in myeloproliferative neoplasms: treatment algorithm
2018.
AB - Myeloproliferative neoplasms (MPNs) are a leading cause of splanchnic vein
thrombosis (SVT). SVT is observed in all MPNs and frequently affects young
patients. Therapy should be addressed to three main goals: preventing thrombosis
recurrence, managing the underlying MPN, and supporting liver dysfunction. Life
long oral anticoagulation with vitamin K antagonists is the cornerstone of the
antithrombotic treatment. However, recurrences of SVT or other thrombosis may
occur in 15-20% of patients. Direct oral anticoagulants can represent an
alternative and preliminary data encourage comparative studies. Survival of
patients with SVT in MPN is primarily influenced by the natural history of the
underlying neoplasms, rather than the SVT event. An aggressive management is
recommended and a treatment algorithm based on the different MPN subtypes is
proposed. Hydroxyurea is the cytoreductive drug of choice in polycythemia vera
and essential thrombocythemia, whereas ruxolitinib is indicated in intermediate
and high-risk patients with myelofibrosis and in PV patients resistant or
intolerant to hydroxyurea. The management of SVT in MPNs requires a
multidisciplinary approach that may include a hematologist, a gastroenterologist,
an interventional radiologist, and a surgeon. In the case of clinical
deterioration despite pharmacological therapy, patients with SVT should be
considered for invasive procedures or liver transplantation.
PMID- 29946156
TI - Increased plasma fatty acid binding protein 4 concentration at the first prenatal
visit and its relevance to preeclampsia.
AB - Preeclampsia affects 2-8% of all pregnancies, and it is associated with
significant perinatal mortality and morbidities including preterm birth and small
for gestational age. We examined whether plasma fatty acid binding protein 4
(FABP4) concentrations are associated with risk of later preeclampsia
development. From March 2015 to May 2016, serum FABP4 was measured in 1486 women
in early pregnancy. The relationship between the levels of FABP4 and preeclampsia
were evaluated using univariate and multivariate regression analysis. The median
plasma concentration of FABP4 at the first prenatal visit was significantly
higher in women in whom preeclampsia developed later compared with those in whom
it did not (P < 0.001). For each 1 unit increase in FABP4 plasma concentration,
the unadjusted and adjusted risk of preeclampsia increased by 8% (odds ratio
(OR): 1.08; 95% confidence interval [CI]: 1.05-1.12) and 4% (1.04; 95% CI: 1.02
1.07), respectively. The addition of FABP4 to established risk factors
significantly improved net reclassification improvement. Increased FABP4 at the
first prenatal visit of gestation independently predicted preeclampsia and
significantly improved reclassification and discrimination. This information is
important to guide public health efforts in preeclampsia prevention.
PMID- 29946155
TI - Beneficial effect of statins in patients receiving chronic hemodialysis following
percutaneous coronary intervention: A nationwide retrospective cohort study.
AB - The cardiovascular diseases are the leading cause of mortality in end-stage renal
disease (ESRD) patients. However, roles of statins are still controversial in
dialysis-dependent ESRD patients regardless of having proven coronary artery
occlusive disease. The aim of this study was to examine the benefit of statin
following percutaneous coronary intervention (PCI) in ESRD patients who have
proven coronary artery occlusive disease. This study was based on the National
Health Insurance Service-National Sample Cohort in South Korea. We included 150
ESRD patients on chronic hemodialysis who underwent PCI with stenting between
2002 and 2013. The primary outcome was a composite of myocardial infarction,
stroke, and all-cause mortality. Multivariate time-dependent Cox regression
analysis were performed, and statin therapy after PCI was treated as a time
dependent variable. During 3.15 +/- 2.71 (mean +/- standard deviation) years of
follow-up, there were 82 patients with primary outcome. The adjusted hazard ratio
for statin use was 0.54 [0.33-0.90] compared to no statin use. This study showed
that statin has significant benefit on reducing adverse events risk in dialysis
dependent ESRD patients after PCI.
PMID- 29946157
TI - Neuroscience of apathy and anhedonia: a transdiagnostic approach.
AB - Apathy and anhedonia are common syndromes of motivation that are associated with
a wide range of brain disorders and have no established therapies. Research using
animal models suggests that a useful framework for understanding motivated
behaviour lies in effort-based decision making for reward. The neurobiological
mechanisms underpinning such decisions have now begun to be determined in
individuals with apathy or anhedonia, providing an important foundation for
developing new treatments. The findings suggest that there might be some shared
mechanisms between both syndromes. A transdiagnostic approach that cuts across
traditional disease boundaries provides a potentially useful means for
understanding these conditions.
PMID- 29946158
TI - Sleep it off.
PMID- 29946159
TI - Efficacy of commercial vaccines against newly emerging avian influenza H5N8 virus
in Egypt.
AB - The newly emerging, highly pathogenic avian influenza (HPAI) H5N8 virus of clade
2.3.4.4 was recently detected in wild birds and domestic poultry in Egypt in the
2016/2017 winter season. Vaccination based on commercial H5 vaccines is used as
an essential control strategy in Egyptian poultry. Here, we studied the efficacy
of the eight most common commercial H5 poultry vaccines in the Egyptian market
and compared them with an experimental vaccine based on the Egyptian LPAI H5N8
virus that was prepared by using reverse genetics. The experimental vaccine and
Re-5 commercial vaccine were able to completely protect chickens and
significantly reduce virus shedding. Our results indicate that most of the
commercial poultry H5 vaccines used in the present study were ineffective because
the seed viruses in these vaccines are genetically distinct from the H5N8 viruses
currently circulating in Egypt. Although some of the commercial vaccines
protected chickens from mortality, they failed to prevent chickens from shedding
the virus. Accordingly, we recommend updating and reinforcing the H5N8 prevention
and control strategies in Egypt. The vaccination strategy should be reconsidered
based on currently circulating viruses.
PMID- 29946161
TI - Celebrate contributions great and small.
PMID- 29946160
TI - Whispering Gallery Mode Enabled Efficiency Enhancement: Defect and Size
Controlled CdSe Quantum Dot Sensitized Whisperonic Solar Cells.
AB - A synergetic approach of employing smooth mesoporous TiO2 microsphere (SMUS-TiO2)
nanoparticulate TiO2 (np-TiO2) composite photoanode, and size and defect
controlled CdSe quantum dots (QD) to achieve high efficiency (eta) in a modified
Gratzel solar cell, quantum dot sensitized whisperonic solar cells (QDSWSC), is
reported. SMUS-TiO2 exhibits whispering gallery modes (WGM) and assists in
enhancing the light scattering. SMUS-TiO2 and np-TiO2 provide conductive path for
efficient photocurrent charge transport and sensitizer loading. The sensitizer
strongly couples with the WGM and significantly enhances the photon absorption to
electron conversion. The efficiency of QDSWSC is shown to strongly depend on the
size and defect characteristics of CdSe QD. Detailed structural, optical,
microstructural and Raman spectral studies on CdSe QD suggest that surface
defects are prominent for size ~2.5 nm, while the QD with size > 4.5 nm are well
crystalline with lower surface defects. QDSWSC devices exhibit an increase in eta
from ~0.46% to eta ~ 2.74% with increasing CdSe QD size. The reported efficiency
(2.74%) is the highest compared to other CdSe based QDSSC made using TiO2
photoanode and I-/I3- liquid electrolyte. The concept of using whispering gallery
for enhanced scattering is very promising for sensitized whisperonic solar cells.
PMID- 29946162
TI - Solving the structure-function puzzle.
PMID- 29946164
TI - Chlamydia trachomatis paralyses neutrophils to evade the host innate immune
response.
AB - Chlamydia trachomatis, an obligate intracellular human pathogen, is a major cause
of sexually transmitted diseases. Infections often occur without symptoms, a
feature that has been attributed to the ability of the pathogen to evade the host
immune response. We show here that C. trachomatis paralyses the host immune
system by preventing the activation of polymorphic nuclear leukocytes (PMNs).
PMNs infected with Chlamydia fail to produce neutrophil extracellular traps and
the bacteria are able to survive in PMNs for extended periods of time. We have
identified the secreted chlamydial protease-like activating factor (CPAF) as an
effector mediating the evasion of the innate immune response since CPAF-deficient
Chlamydia activate PMNs and are subsequently efficiently killed. CPAF suppresses
the oxidative burst and interferes with chemical-mediated activation of
neutrophils. We identified formyl peptide receptor 2 (FPR2) as a target of CPAF.
FPR2 is cleaved by CPAF and released from the surface of PMNs. In contrast to
previously described subversion mechanisms that mainly act on already activated
PMNs, we describe here details of how Chlamydia actively paralyses PMNs,
including the formation of neutrophil extracellular traps, to evade the host's
innate immune response.
PMID- 29946163
TI - Modelling Cryptosporidium infection in human small intestinal and lung organoids.
AB - Stem-cell-derived organoids recapitulate in vivo physiology of their original
tissues, representing valuable systems to model medical disorders such as
infectious diseases. Cryptosporidium, a protozoan parasite, is a leading cause of
diarrhoea and a major cause of child mortality worldwide. Drug development
requires detailed knowledge of the pathophysiology of Cryptosporidium, but
experimental approaches have been hindered by the lack of an optimal in vitro
culture system. Here, we show that Cryptosporidium can infect epithelial
organoids derived from human small intestine and lung. The parasite propagates
within the organoids and completes its complex life cycle. Temporal analysis of
the Cryptosporidium transcriptome during organoid infection reveals dynamic
regulation of transcripts related to its life cycle. Our study presents organoids
as a physiologically relevant in vitro model system to study Cryptosporidium
infection.
PMID- 29946165
TI - Specialized proteomic responses and an ancient photoprotection mechanism sustain
marine green algal growth during phosphate limitation.
AB - Marine algae perform approximately half of global carbon fixation, but their
growth is often limited by the availability of phosphate or other nutrients1,2.
As oceans warm, the area of phosphate-limited surface waters is predicted to
increase, resulting in ocean desertification3,4. Understanding the responses of
key eukaryotic phytoplankton to nutrient limitation is therefore critical5,6. We
used advanced photo-bioreactors to investigate how the widespread marine green
alga Micromonas commoda grows under transitions from replete nutrients to chronic
phosphate limitation and subsequent relief, analysing photosystem changes and
broad cellular responses using proteomics, transcriptomics and biophysical
measurements. We find that physiological and protein expression responses
previously attributed to stress are critical to supporting stable exponential
growth when phosphate is limiting. Unexpectedly, the abundance of most proteins
involved in light harvesting does not change, but an ancient light-harvesting
related protein, LHCSR, is induced and dissipates damaging excess absorbed light
as heat throughout phosphate limitation. Concurrently, a suite of uncharacterized
proteins with narrow phylogenetic distributions increase multifold. Notably, of
the proteins that exhibit significant changes, 70% are not differentially
expressed at the mRNA transcript level, highlighting the importance of post
transcriptional processes in microbial eukaryotes. Nevertheless, transcript
protein pairs with concordant changes were identified that will enable more
robust interpretation of eukaryotic phytoplankton responses in the field from
metatranscriptomic studies. Our results show that P-limited Micromonas responds
quickly to a fresh pulse of phosphate by rapidly increasing replication, and that
the protein network associated with this ability is composed of both conserved
and phylogenetically recent proteome systems that promote dynamic phosphate
homeostasis. That an ancient mechanism for mitigating light stress is central to
sustaining growth during extended phosphate limitation highlights the possibility
of interactive effects arising from combined stressors under ocean change, which
could reduce the efficacy of algal strategies for optimizing marine
photosynthesis.
PMID- 29946167
TI - Specific activation of mGlu2 induced IGF-1R transactivation in vitro through FAK
phosphorylation.
AB - Metabotropic glutamate receptor 2 (mGlu2) belongs to the group-II metabotropic
glutamate (mGlu) receptors and is a neurotransmitter G protein-coupled receptor.
The group-II mGlu receptors are promising antipsychotic targets, but the specific
role of mGlu2 signaling remains unclear. Receptor tyrosine kinases (RTKs) are
also believed to participate in brain pathogenesis. To investigate whether there
is any communication between mGlu2 and RTKs, we generated a CHO-mGlu2 cell line
that stably expresses mGlu2 and showed that activation of mGlu2 by LY379268, a
group II mGlu agonist, was able to transactivate insulin-like growth factor 1
receptor (IGF-1R). We further determined that the Gi/o protein, Gbetagamma
subunits, phospholipase C, and focal adhesion kinase (FAK) were involved in the
IGF-1R transactivation signaling axis, which further induced the phosphorylation
of extracellular signal-regulated kinase1/2 (ERK1/2) and cAMP response element
binding protein. In primary mouse cortical neurons, similar signaling pathways
were observed when mGlu2 were stimulated by LY487379, an mGlu2 positive
allosteric modulator. Transactivation of IGF-1R through FAK in response to mGlu2
should provide a better understanding of the association of mGlu2 with brain
disease.
PMID- 29946166
TI - The threshold elemental ratio of carbon and phosphorus of Daphnia magna and its
connection to animal growth.
AB - The growth of animal consumers is affected by the balance of elements in their
diet with the transition between limitation by one element to another known as
the threshold elemental ratio (TER). Precise estimates of TERs with known levels
of uncertainty have yet to be generated for most zooplankton consumers. We
determined the TER for carbon (C) and phosphorus (P) in for a common lake
zooplankter, Daphnia magna, using experimental measurements and theoretical
considerations. Daphnia growth responses to food C:P ratios across a relatively
narrow range (80-350) generated an empirical estimate of TERC:P of 155 +/- 14.
While this TER matched our modelled estimate of TERC:P (155 +/- 16), it was lower
than previous estimates of this dietary transition point. No threshold was found
when we examined daphnid body C:N or C:P ratios in response to changing food C:P
ratios, which indicates P-limitation at even lower food C:P ratios. Our results
provide strong evidence that D. magna is likely to experience acute P-limitation
when food C:P ratios exceed even relatively low ratios (~155). Our model further
demonstrated that while physiological adjustments may reduce the likelihood of P
limitation or reduce its intensity, these changes in animal material processing
would be accompanied by reduced maximum growth rates.
PMID- 29946168
TI - Author Correction: The evolutionary history of vertebrate RNA viruses.
AB - Change history: In this Article, author Li Liu should be associated with
affiliation number 5 (College of Marine Sciences, South China Agricultural
University, Guangzhou, Guangdong, China), rather than affiliation number 4
(Wenzhou Center for Disease Control and Prevention, Wenzhou, Zhejiang, China).
This has been corrected online.
PMID- 29946169
TI - Addendum: Freezing on a sphere.
PMID- 29946170
TI - Publisher Correction: Deterministic delivery of remote entanglement on a quantum
network.
AB - Change history: In this Letter, the received date should be 20 December 2017,
instead of 27 April 2018. This has been corrected online.
PMID- 29946171
TI - Publisher Correction: Magnetic edge states and coherent manipulation of graphene
nanoribbons.
AB - In Fig. 1 of this Letter, there should have been two nitrogen (N) atoms at the
1,3-positions of all the blue chemical structures (next to the oxygen atoms),
rather than one at the 2-position. The figure has been corrected online, and the
original incorrect figure is shown as Supplementary Information to the
accompanying Amendment.
PMID- 29946172
TI - C2orf71a/pcare1 is important for photoreceptor outer segment morphogenesis and
visual function in zebrafish.
AB - Mutations in C2orf71 are causative for autosomal recessive retinitis pigmentosa
and occasionally cone-rod dystrophy. We have recently discovered that the protein
encoded by this gene is important for modulation of the ciliary membrane through
the recruitment of an actin assembly module, and have therefore renamed the gene
to PCARE (photoreceptor cilium actin regulator). Here, we report on the
identification of two copies of the c2orf71/pcare gene in zebrafish, pcare1 and
pcare2. To study the role of the gene most similar to human PCARE, pcare1, we
have generated a stable pcare1 mutant zebrafish model (designated pcare1
rmc100/rmc100 ) in which the coding sequence was disrupted using CRISPR/Cas9
technology. Retinas of both embryonic (5 dpf) and adult (6 mpf) pcare1
rmc100/rmc100 zebrafish display a clear disorganization of photoreceptor outer
segments, resembling the phenotype observed in Pcare-/- mice. Optokinetic
response and visual motor response measurements indicated visual impairment in
pcare1 rmc100/rmc100 zebrafish larvae at 5 dpf. In addition, electroretinogram
measurements showed decreased b-wave amplitudes in pcare1 rmc100/rmc100 zebrafish
as compared to age- and strain-matched wild-type larvae, indicating a defect in
the transretinal current. Altogether, our data show that lack of pcare1 causes a
retinal phenotype in zebrafish and indicate that the function of the PCARE gene
is conserved across species.
PMID- 29946173
TI - The C.L.A.M.P. Nephrometry score: A system for preoperative assessment of
laparoscopic partial nephrectomy with Segmental Renal Artery Clamping.
AB - Laparoscopic partial nephrectomy with segmental renal artery clamping is
associated with a less warm ischemic injury and better postoperative affected
renal function compared with main renal artery clamping. However, its indication
remains unclear. We established a standardized nephrometry scoring system (The
C.L.A.M.P. Nephrometry Score) to evaluate its flexibility in preoperative
assessment. This scoring system based on 5 components. The ranking (C)oefficient
of each score and the (L)ocation of the clamping position of the target artery
and areas of the target artery entering the renal sinus: (A)nterior boundary,
(M)ulti-boundary and (P)osterior boundary. We applied this system to analyze data
from 106 consecutive patients who underwent SRAC during LPN and divided these
patients into 3 groups based on their C.L.A.M.P. scores. The rate of conversion
to main renal artery clamping and clamping success rate and the affected side GFR
reduction showed significant differences among the groups (P < 0.001). However,
parameters such as blood loss, Warm ischemia time and postoperative
hospitalization were not significantly different. The C.L.A.M.P. nephrometry
score shows strong ability in distinguishing different complexities of artery
characteristics and plays a promising role in identifying patients who are
suitable for the SRAC technique.
PMID- 29946174
TI - A Shared Decision Approach to Chronic Abdominal Pain Based on Cine-MRI: A
Prospective Cohort Study.
AB - OBJECTIVES: Chronic abdominal pain develops in 11-20% of patients undergoing
abdominal surgery, partly owing to post-operative adhesions. In this study we
evaluate results of a novel diagnostic and therapeutic approach for pain
associated with adhesions. METHODS: Prospective cohort study including patients
with a history of abdominal surgery referred to the outpatient clinic of a
tertiary referral center for the evaluation of chronic abdominal pain. Subgroups
were made based on outcome of adhesion mapping with cine-MRI and shared decision
making. In operatively managed cases, anti-adhesion barriers were applied after
adhesiolysis. Long-term results for pain were evaluated by a questionnaire.
RESULTS: A total of 106 patients were recruited. Seventy-nine patients had
adhesions on cine-MRI, 45 of whom underwent an operation. Response rate to follow
up questionnaire was 86.8%. In the operative group (Group 1), the number of
negative laparoscopies was 3 (6%). After a median of 19 (range 6-47) months
follow-up, 80.0% of patients in group 1 reported improvement of pain, compared
with 42.9% in patients with adhesions on cine-MRI who declined surgery (group 2),
and 26.3% in patients with no adhesions on cine-MRI (group 3), P = 0.002.
Consultation of medical specialists was significantly lower in group 1 compared
with groups 2 and 3 (35.7 vs. 65.2 vs. 58.8%; P = 0.023). CONCLUSION: We
demonstrate long-term pain relief in two-thirds of patients with chronic pain
likely caused by adhesions, using cine-MRI and a shared decision-making process.
Long-term improvement of pain was achieved in 80% of patients who underwent
surgery with concurrent application of an anti-adhesion barrier.
PMID- 29946175
TI - Microenvironment Eradication of Hepatitis C: A Novel Treatment Paradigm.
AB - OBJECTIVES: Prisons are major reservoirs of hepatitis C virus (HCV) in which a
therapeutic approach has been particularly difficult so far. Our aim was to
create a permanent program of HCV elimination in a prison based on a "test and
treat" strategy. METHODS: This open-label clinical trial was conducted in the
Spanish prison "El Dueso" between May 2016 and July 2017. Viremic patients were
treated with a ledipasvir-sofosbuvir regimen (8-12 weeks) according to the 2015
Spanish Guidelines. A teleconsultation program was established to follow-up
patients from the hospital. Non-responders were submitted for a phylogenetic
analysis and offered retreatment. An evaluation of new cases of HCV infection was
performed every 6 months and upon release in all inmates. RESULTS: 847 (99.5%)
inmates accepted to participate. HCV antibodies were present in 110 (13.0%) and
86 (10.2%) had detectable viremia. Most of them were genotype 1 or 3 (82.6%) and
had =1%, >=5%, >=10%, and >=50%. Mean
overall agreement for all indications was 0.87-0.99. Inter- and intra-assay of
scoring/classification repeatability was 100%. Analysis of PD-L1 expression
levels using laboratory-developed immunohistochemistry assays with 28-8 antibody
may be permissible if the platform is validated using reference samples with
defined expression levels.
PMID- 29946186
TI - Phenotype-loci associations in networks of patients with rare disorders:
application to assist in the diagnosis of novel clinical cases.
AB - Copy number variations (CNVs) are genomic structural variations (deletions,
duplications, or translocations) that represent the 4.8-9.5% of human genome
variation in healthy individuals. In some cases, CNVs can also lead to disease,
being the etiology of many known rare genetic/genomic disorders. Despite the last
advances in genomic sequencing and diagnosis, the pathological effects of many
rare genetic variations remain unresolved, largely due to the low number of
patients available for these cases, making it difficult to identify consistent
patterns of genotype-phenotype relationships. We aimed to improve the
identification of statistically consistent genotype-phenotype relationships by
integrating all the genetic and clinical data of thousands of patients with rare
genomic disorders (obtained from the DECIPHER database) into a phenotype-patient
genotype tripartite network. Then we assessed how our network approach could help
in the characterization and diagnosis of novel cases in clinical genetics. The
systematic approach implemented in this work is able to better define the
relationships between phenotypes and specific loci, by exploiting large-scale
association networks of phenotypes and genotypes in thousands of rare disease
patients. The application of the described methodology facilitated the diagnosis
of novel clinical cases, ranking phenotypes by locus specificity and reporting
putative new clinical features that may suggest additional clinical follow-ups.
In this work, the proof of concept developed over a set of novel clinical cases
demonstrates that this network-based methodology might help improve the precision
of patient clinical records and the characterization of rare syndromes.
PMID- 29946187
TI - The Na/K-ATPase Oxidant Amplification Loop Regulates Aging.
AB - As aging involves oxidant injury, we examined the role of the recently described
Na/K-ATPase oxidant amplification loop (NKAL). First, C57Bl6 old mice were given
a western diet to stimulate oxidant injury or pNaKtide to antagonize the NKAL.
The western diet accelerated functional and morphological evidence for aging
whereas pNaKtide attenuated these changes. Next, human dermal fibroblasts (HDFs)
were exposed to different types of oxidant stress in vitro each of which
increased expression of senescence markers, cell-injury, and apoptosis as well as
stimulated the NKAL. Further stimulation of the NKAL with ouabain augmented
cellular senescence whereas treatment with pNaKtide attenuated it. Although N
Acetyl Cysteine and Vitamin E also ameliorated overall oxidant stress to a
similar degree as pNaKtide, the pNaKtide produced protection against senescence
that was substantially greater than that seen with either antioxidant. In
particular, pNaKtide appeared to specifically ameliorate nuclear oxidant stress
to a greater degree. These data demonstrate that the NKAL is intimately involved
in the aging process and may serve as a target for anti-aging interventions.
PMID- 29946188
TI - Sodium orthovanadate overcomes sorafenib resistance of hepatocellular carcinoma
cells by inhibiting Na+/K+-ATPase activity and hypoxia-inducible pathways.
AB - The resistance to sorafenib highly affects its clinical benefits for treating
hepatocellular carcinoma (HCC). Sodium orthovanadate (SOV) is a phosphate analog
that displays anti-cancer activities against various types of malignancies
including HCC. The present study has demonstrated that SOV is able to overcome
sorafenib resistance and strengthens sorafenib in suppressing sorafenib-resistant
HCC cells in vitro and in animal models. Similar to its action on parental HCC
cells, SOV induced cell cycle arrest at G2/M phases by regulating cyclin B1 and
cyclin-dependent kinase 1, and apoptosis by reducing mitochondrial membrane
potential, in sorafenib-resistant HCC cells. More importantly, SOV inhibited
ATPase activity, which was significantly elevated in sorafenib-resistant HCC
cells. SOV also reduced the expression of HIF-1alpha and HIF-2alpha and their
nuclear translocation, resulting in downregulation of their downstream factors
including vascular endothelial growth factor, lactate dehydrogenase-A and glucose
transporter 1. Its ability to inhibit ATPase activity and hypoxia-inducible
pathways enabled SOV to efficiently suppress both normoxic and hypoxic cells,
which compose cancer cell populations inside sorafenib-resistant HCC tumors. The
present results indicate that SOV may be a potent candidate drug for overcoming
the resistance to sorafenib in treating HCC.
PMID- 29946189
TI - Homomultimerization of mutant calreticulin is a prerequisite for MPL binding and
activation.
AB - Studies have previously shown that mutant calreticulin (CALR), found in a subset
of patients with myeloproliferative neoplasms (MPNs), interacts with and
subsequently promotes the activation of the thrombopoietin receptor (MPL).
However, the molecular mechanism behind the activity of mutant CALR remains
unknown. Here we show that mutant, but not wild-type, CALR interacts to form a
homomultimeric complex. This intermolecular interaction among mutant CALR
proteins depends on their carboxyl-terminal domain, which is generated by a
unique frameshift mutation found in patients with MPN. With a competition assay,
we demonstrated that the formation of mutant CALR homomultimers is required for
the binding and activation of MPL. Since association with MPL is required for the
oncogenicity of mutant CALR, we propose a model in which the constitutive
activation of the MPL downstream pathway by mutant CALR multimers induces the
development of MPN. This study provides a potential novel therapeutic strategy
against mutant CALR-dependent tumorigenesis via targeting the intermolecular
interaction among mutant CALR proteins.
PMID- 29946190
TI - Late mortality after allogeneic blood or marrow transplantation in childhood for
leukemia: a report from the Blood or Marrow Transplant Survivor Study-2.
PMID- 29946191
TI - Diagnostic algorithm for lower-risk myelodysplastic syndromes.
AB - Rapid advances over the past decade have uncovered the heterogeneous genomic and
immunologic landscape of myelodysplastic syndromes (MDS). This has led to notable
improvements in the accuracy and timing of diagnosis and prognostication of MDS,
as well as the identification of possible novel targets for therapeutic
intervention. For the practicing clinician, however, this increase in genomic,
epigenomic, and immunologic knowledge needs consideration in a "real-world"
context to aid diagnostic specificity. Although the 2016 revision to the World
Health Organization classification for MDS is comprehensive and timely, certain
limitations still exist for day-to-day clinical practice. In this review, we
describe an up-to-date diagnostic approach to patients with suspected lower-risk
MDS, including hypoplastic MDS, and demonstrate the requirement for an
"integrated" diagnostic approach. Moreover, in the era of rapid access to massive
parallel sequencing platforms for mutational screening, we suggest which patients
should undergo such analyses, when such screening should be performed, and how
those data should be interpreted. This is particularly relevant given the recent
findings describing age-related clonal hematopoiesis.
PMID- 29946192
TI - Coexpression profile of leukemic stem cell markers for combinatorial targeted
therapy in AML.
AB - Targeted immunotherapy in acute myeloid leukemia (AML) is challenged by the lack
of AML-specific target antigens and clonal heterogeneity, leading to unwanted on
target off-leukemia toxicity and risk of relapse from minor clones. We
hypothesize that combinatorial targeting of AML cells can enhance therapeutic
efficacy without increasing toxicity. To identify target antigen combinations
specific for AML and leukemic stem cells, we generated a detailed protein
expression profile based on flow cytometry of primary AML (n = 356) and normal
bone marrow samples (n = 34), and a recently reported integrated normal tissue
proteomic data set. We analyzed antigen expression levels of CD33, CD123, CLL1,
TIM3, CD244 and CD7 on AML bulk and leukemic stem cells at initial diagnosis (n =
302) and relapse (n = 54). CD33, CD123, CLL1, TIM3 and CD244 were ubiquitously
expressed on AML bulk cells at initial diagnosis and relapse, irrespective of
genetic characteristics. For each analyzed target, we found additional expression
in different populations of normal hematopoiesis. Analyzing the coexpression of
our six targets in all dual combinations (n = 15), we found CD33/TIM3 and
CLL1/TIM3 to be highly positive in AML compared with normal hematopoiesis and non
hematopoietic tissues. Our findings indicate that combinatorial targeting of
CD33/TIM3 or CLL1/TIM3 may enhance therapeutic efficacy without aggravating
toxicity in immunotherapy of AML.
PMID- 29946193
TI - Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by
downregulating miR-34a in B-cell lymphomas.
AB - Cancer cells subvert host immune surveillance by altering immune checkpoint (IC)
proteins. Some Epstein-Barr virus (EBV)-associated tumors have higher Programmed
Cell Death Ligand, PD-L1 expression. However, it is not known how EBV alters ICs
in the context of its preferred host, the B lymphocyte and in derived lymphomas.
Here, we found that latency III-expressing Burkitt lymphoma (BL), diffuse large B
cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1.
In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. Latency III
expressing DLBCL biopsies showed high levels of PD-L1. The PD-L1 targeting
oncosuppressor microRNA miR-34a was downregulated in EBNA2-transfected lymphoma
cells. We identified early B-cell factor 1 (EBF1) as a repressor of miR-34a
transcription. Short hairpin RNA (shRNA)-mediated knockdown of EBF1 was
sufficient to induce miR-34a transcription, which in turn reduced PD-L1. MiR-34a
reconstitution in EBNA2-transfected DLBCL reduced PD-L1 expression and increased
its immunogenicity in mixed lymphocyte reactions (MLR) and in three-dimensional
biomimetic microfluidic chips. Given the importance of PD-L1 inhibition in
immunotherapy and miR-34a dysregulation in cancers, our findings may have
important implications for combinatorial immunotherapy, which include IC
inhibiting antibodies and miR-34a, for EBV-associated cancers.
PMID- 29946194
TI - The influence of diabetes and antidiabetic medications on the risk of pancreatic
cancer: a nationwide population-based study in Korea.
AB - This study investigated the effects of diabetes and antidiabetic medications on
the risk of pancreatic cancer(PaC). We extracted data on Koreans with newly
diagnosed diabetes and selected age- and sex-matched controls provided by the
National Health Insurance Corporation. Incident PaC was defined as a new
registration in the Korea Central Cancer Registry under ICD-10 C25 with admission
history until 2015. During 19,429,617.1 person-years, 8,589 PaCs were identified
in 1,005,409 subjects for diabetes group and 4,021,636 subjects for control
group. The diabetes group showed more than a two-fold risk for PaC compared with
the control group. Among antidiabetic medications, metformin, thiazolidinedione,
and dipeptidyl peptidase-4 inhibitor exposure was associated with decreased risk
for future PaC(hazard ratio[95% confidence interval] = 0.86[0.77-0.96], 0.82[0.68
0.98], 0.57[0.51-0.64], respectively), whereas sulfonylurea and insulin exposure
was related to increased risk(hazard ratio[95% CI] = 1.73[1.57-1.91], 2.86[1.43
5.74], respectively) compared to subjects with no drug exposure. Moreover,
subjects with dual exposure history to metformin plus thiazolidinedione or
metformin plus dipeptidyl peptidase-4 inhibitor had a lower risk of PaC compared
to metformin-only treated subjects. In conclusion, Korean adults with diabetes
are at higher risk of PaC compared with nondiabetic individuals, and this risk
may be modified by antidiabetic medications.
PMID- 29946196
TI - Assessment of the type of farmers' low back pain.
AB - BACKGROUND: Spinal overload among blue-collar workers occurs most frequently in
the lumbar spine. Long-lasting spinal overload results in pain syndromes leading
to limitations in everyday and professional life. MATERIAL AND METHODS: The
research included 106 adult males working as farmers for at least 10 years. The
control group included 50 male white-collar workers. Four research tools were
used: an interview questionnaire, a questionnaire assessing pain intensity and
limitations in everyday functioning of study participants, a Numeric Rating Scale
(NRS) measuring pain intensity and Oswestry Disability Index. RESULTS: The
research revealed that as many as 86% of the farmers (91 individuals) experienced
low back pain. In the control group only 64% of all the white-collar workers
complained of pain in this part of the spine. The farmers defined their low back
pain as constant pain or stiffness significantly more often. In addition, they
reported hip pain radiating to one or 2 legs and experienced chronic and acute
back pain more frequently. The total time in which they experienced this pain was
usually 11-20 years. The correlation between pain intensity measured on a numeric
scale and the level of disability of farmers was revealed. CONCLUSIONS: The
research revealed that individual farmers complained of low back pain
significantly more often. The pain was usually defined as constant pain, chronic
pain, acute pain or hip pain radiating to legs. Med Pr 2018;69(4):355-364.
PMID- 29946195
TI - Ixodes scapularis does not harbor a stable midgut microbiome.
AB - Hard ticks of the order Ixodidae serve as vectors for numerous human pathogens,
including the causative agent of Lyme Disease Borrelia burgdorferi. Tick
associated microbes can influence pathogen colonization, offering the potential
to inhibit disease transmission through engineering of the tick microbiota. Here,
we investigate whether B. burgdorferi encounters abundant bacteria within the
midgut of wild adult Ixodes scapularis, its primary vector. Through the use of
controlled sequencing methods and confocal microscopy, we find that the majority
of field-collected adult I. scapularis harbor limited internal microbial
communities that are dominated by endosymbionts. A minority of I. scapularis
ticks harbor abundant midgut bacteria and lack B. burgdorferi. We find that the
lack of a stable resident midgut microbiota is not restricted to I. scapularis
since extension of our studies to I. pacificus, Amblyomma maculatum, and
Dermacentor spp showed similar patterns. Finally, bioinformatic examination of
the B. burgdorferi genome revealed the absence of genes encoding known
interbacterial interaction pathways, a feature unique to the Borrelia genus
within the phylum Spirochaetes. Our results suggest that reduced selective
pressure from limited microbial populations within ticks may have facilitated the
evolutionary loss of genes encoding interbacterial competition pathways from
Borrelia.
PMID- 29946197
TI - Association of TNF-alpha-308 G > A and -238G > A polymorphisms with knee
osteoarthritis risk: A case-control study and meta-analysis.
AB - Objective: A comprehensive search on electronic databases was conducted to
identify all eligible studies of TNF-alpha polymorphisms and knee osteoarthritis
(OA). Methods: Eight studies on TNF-alpha -308 G > A and three on TNF-alpha -238G
> A polymorphism were identified. Results: Overall, the pooled ORs indicated that
neither TNF-alpha -238G > A nor -238G > A polymorphism was associated with knee
OA risk. Similarly, in the stratified analysis by ethnicity, no significant
association was found. Conclusion: This meta-analysis results inconsistent with
the previous meta-analyses showed that the TNF-alpha -308 G > A and -238G > A
polymorphisms may not be associated with the susceptibility to knee OA.
PMID- 29946198
TI - Arthroscopic aproach of femoroacetabular impigement: Early clinical outcomes. A
multicentric study.
AB - Femoroacetabular impingement (FAI) is a common cause of hip joint dysfunction and
pain in adults aged between 30-60 years. The main objective of the study is to
evaluate the short term clinical outcome of hip arthroscopy in patients diagnosed
with FAI. A total of 105 patients were studied. This minimal invasive technique
has shown to be highly effective in comparison to open surgery in young patients.
PMID- 29946199
TI - Long-term results after surgical treatment of subacromial pain syndrome with or
without rotator cuff tear.
AB - Purpose: Some studies suggest a common degenerative path might contribute to a
range of shoulder diseases involving subacromial pain syndrome and full-thickness
rotator cuff tears. One could therefore theorize arthroscopic subacromial
decompression and rotator cuff repair as interventions at different stages of a
degenerative shoulder disease. Few studies have compared long-term outcomes after
these two procedures. Method: Matched case-controls undergoing arthroscopic
rotator cuff repair combined with subacromial decompression (N = 180) or
subacromial decompression only (N = 180) were evaluated pre- and 7.5 years
postoperatively using QuickDASH score, VAS of function, VAS of pain and VAS of
satisfaction. New surgery and complications were recorded. Baseline
characteristics were related to outcomes to investigate predictors of good/poor
outcome. Results: A general improvement from baseline was seen - from 51 to 14
(QuickDASH) in the combined group and from 53 to 16 in the decompression only
group. No differences in outcomes were seen between groups (n.s.). Age above 55
at surgery predicted better VAS of function (P = .04) while acute onset of
symptoms predicted better QuickDASH in the combined group (P = 0.03). None in the
decompression group had undergone later rotator cuff repair. Conclusion: Major
improvements in pain/function were seen at mid- to long-term after isolated
arthroscopic subacromial decompression and combined decompression/rotator cuff
repair. Several patient-specific factors predicting worse outcomes were
identified.
PMID- 29946200
TI - Functional outcome of open acromioclavicular joint stabilization for instability
following distal clavicle resection.
AB - Background: Acromioclavicular joint instability following distal clavicle
resection can result in considerable pain and dysfunction. Method: We present a
review of 13 patients who underwent ACJ stabilization following one or more
distal clavicle resection procedures. Results: The mean Quick DASH and CM scores
were 26(0-57) and 73(46-100) respectively. All but one patient reported an
improvement in the pain component of their CM score and in the work component of
the Quick DASH score. Discussion: Open ACJ stabilization to treat instability
following distal clavicle resection resulted in improved functional scores, pain
scores and facilitated return to work in most patients.Level of evidence IV.
PMID- 29946201
TI - A comparison of two different navigated hip replacement techniques on leg length
discrepancy.
AB - We hypothesised that a femoral array placed into bone or an external (pinless)
reference marker made no difference to leg length discrepancy in patients
undergoing navigated total hip arthroplasty. Consecutive patients undergoing
navigated total hip arthroplasty. 162 patients. No statistical difference between
preoperative leg length discrepancy (p = 0.524). Mean intraoperative change was
3.7 mm and 4.6 mm (p = 0.262). The mean change in leg length measure post
operatively was 4.2 mm and 4.1 mm (p = 0.656). No significant difference in leg
length discrepancy between a pinless reference markers and a femoral array placed
into the bone.
PMID- 29946202
TI - A review of literature: Mosaicoplasty as an alternative treatment for resection
of patellar osteoid osteoma and cartilage reconstruction.
AB - Osteoid osteoma is an uncommon benign tumor and causes severe pain, being worse
at night, that responds dramatically to nonsteroidal anti-inflammatory
medications. An osteoid osteoma of the patella is very rare and if it arise close
to chondral surface differential diagnosis may be challenging. In three patients
the osteoid osteoma was completely excised by nidus removal by mosaicoplasty set
with open surgical technique. The patients were followed up in average for 31 (16
48 months) months with annual clinical and radiographic evaluations. There were
no relapse of the pain and no residual recurrent tumor. The aim of the treatment
for osteoid osteoma is to remove entire nidus by open surgical excision or by
percutaneous procedures such as percutaneous radiofrequency and laser ablation.
Mosaicoplasty is a good alternative for treatment of osteoid osteoma of the
patella in the subchondral bone.
PMID- 29946203
TI - Fresh frozen femoral head osteochondral allograft reconstruction of the humeral
head reverse hill sachs lesion.
PMID- 29946204
TI - Calcifying Tendinitis of Shoulder: A Concise Review.
AB - Calcifying Tendinitis (CT) shoulder a self limiting disorder characterized by
deposition of calcium salts in rotator cuff muscles. The main symptom being pain
followed by activity restriction resolving on its own in most cases. Symptomatic
patients are initially managed by NSAIDs, Physiotherapy, Corticosteroid
injections. ESWT involves acoustic waves causing fragmentation of deposits with
pain releif. Ultrasound guided needling barbotage have shown promising results.
Arthroscopic excision remains the definitive management for patients associated
with complications as cuff tear and for uncomplicated patients. In calcifying
tendinitis the initial evaluation, maintenance of function and appropriate choice
of treatment modalities determines the prognosis.
PMID- 29946205
TI - The mind-body Cartesian dualism and psychiatry.
AB - The French philosopher Rene Descartes (1596-1650) argued that the natures of mind
and body are completely different from one another and that each could exist by
itself. How can these two structures with different natures causally interact in
order to give rise to a human being with voluntary bodily motions and sensations?
Even today, the problem of mind-body causal interaction remains a matter of
debate.
PMID- 29946206
TI - Historical epistemology of the body-mind interaction in psychiatry.
AB - This paper deals with the history of the relationship between the mind-body
dualism and the epistemology of madness. Earlier versions of such dualism posed
little problem in regard to the manner of their communication. The Cartesian view
that mind and body did, in fact, name different substances introduced a problem
of incommunicability that is yet to be resolved. Earlier views that madness may
be related to changes in the brain began gaining empirical support during the
17th century. Writers on madness chose to resolve the mind-body problem
differently Some stated that such communication was not needed; others, that mind
was a redundant concept, as madness could be fully explained by structural
changes in the brain; and yet others described psychological spaces for madness
to inhabit as a symbolic conflict. The epistemology of the neurosciences bypasses
the conundrum, as it processes all together the variables representing the brain,
subjectivity, and behavior and bridges the "philosophical" gap by means of
correlational structures.
PMID- 29946207
TI - Psycho-oncology.
AB - Medical progress, the improvement of general living conditions, and an increase
in life expectancy have led to an increase in the general prevalence of oncologic
disease. More importantly, more and more patients survive cancer or live with the
disease for long periods of time. While the battle for survivorship is
continuously being fought, improving patients' quality of life has come to the
fore. Psychosocial issues may modulate the course of the disease, but mainly have
a deep impact on patients' physical and mental wellbeing. Psycho-oncology has
risen as a relatively new interdisciplinary field with the aim of addressing
these issues and providing support for patients confronting numerous challenges
throughout the different stages of the disease. In this article, we provide an
overview of the current knowledge of body-mind interactions in cancer and an
outline of the broad spectrum of psycho-oncologic care, with a special focus on
the treatment of pain, fatigue, sexual issues, and fear of progression.
PMID- 29946208
TI - Management of somatic symptom disorder.
AB - This review paper gives an overview of the management of somatic symptom
disorder. It starts with a description of the clinical problem of patients with
persistent bodily distress, discusses classificatory, epidemiological, and
etiological issues and then describes the evidence and practical principles of
dealing with these patients who are often seen as "difficult" to treat. It is
concluded that the best-suited approach is stepped care with close cooperation of
primary care, a somatic specialist, and mental health care professionals
operating on the basis of a biopsychosocial model of integrating somatic as well
as psychosocial determinants of distress and therapeutic factors.
PMID- 29946209
TI - The intriguing relationship between coronary heart disease and mental disorders.
AB - Coronary heart disease (CHD) and mental illness are among the leading causes of
morbidity and mortality worldwide. Decades of research has revealed several, and
sometimes surprising, links between CHD and mental illness, and has even
suggested that both may actually cause one another. However, the precise nature
of these links has not yet been clearly established. The goal of this paper,
therefore, is to comprehensively review and discuss the state-of-the-art nature
of the epidemiological and pathophysiological aspects of the bidirectional links
between mental illness and CHD. This review demonstrates that there exists a
large body of epidemiological prospective data showing that people with severe
mental illness, including schizophrenia, bipolar disorder, and major depressive
disorder, as a group, have an increased risk of developing CHD, compared with
controls [adjusted hazard ratio (adjHR)=1.54; 95% CI: 1.30-1.82, P<0.0001].
Anxiety symptoms or disorders (Relative Risk (RR)=1.41, 95% CI: 1.23-1.61,
P<0.0001), as well as experiences of persistent or intense stress or
posttraumatic stress disorder (PTSD) (adjHR=1.27, 95% CI: 1.08-1.49), although to
a lesser degree, may also be independently associated with an increased risk of
developing CHD. On the other hand, research also indicates that these
symptoms/mental diseases are common in patients with CHD and may be associated
with a substantial increase in cardiovascular morbidity and mortality. Finally,
mental diseases and CHD appear to have a shared etiology, including biological,
behavioral, psychological, and genetic mechanisms.
PMID- 29946210
TI - The relationship between stress and infertility.
AB - The relationship between stress and infertility has been debated for years. Women
with infertility report elevated levels of anxiety and depression, so it is clear
that infertility causes stress. What is less clear, however, is whether or not
stress causes infertility. The impact of distress on treatment outcome is
difficult to investigate for a number of factors, including inaccurate self
report measures and feelings of increased optimism at treatment onset. However,
the most recent research has documented the efficacy of psychological
interventions in lowering psychological distress as well as being associated with
significant increases in pregnancy rates. A cognitive-behavioral group approach
may be the most efficient way to achieve both goals. Given the distress levels
reported by many infertile women, it is vital to expand the availability of these
programs.
PMID- 29946211
TI - Depression and diabetes.
AB - The comorbidity of mental and physical disorders is a major challenge for health
care worldwide. Its prevalence is increasing and is likely to continue to grow
due to the increase in life expectancy and a variety of other reasons. The
comorbidity of depression and diabetes can be seen as a prototypical example of
mental/physical comorbidity. The prevalence of both conditions is growing, and
depression is twice as frequent in people with diabetes compared with those
without diabetes. Health services are by and large inadequately prepared to deal
with comorbid depression and diabetes, and the increasing specialization (and
fragmentation) of medicine will probably make things worse. This paper reviews
the epidemiology and risk factors of the comorbidity of depression and diabetes
and describes areas that should be given attention in order to reduce problems
arising as a result of the comorbidity of these two conditions.
PMID- 29946212
TI - Facts and myths pertaining to fibromyalgia.
AB - Fibromyalgia (FM) is characterized by chronic widespread pain, unrefreshing
sleep, physical exhaustion, and cognitive difficulties. It occurs in all
populations throughout the world, with prevalence between 2% and 4% in general
populations. Definition, pathogenesis, diagnosis, and treatment of FM remain
points of contention, with some even contesting its existence. The various
classification systems according to pain medicine, psychiatry, and neurology
(pain disease; persistent somatoform pain disorder; masked depression; somatic
symptom disorder; small fiber neuropathy; brain disease) mostly capture only some
components of this complex and heterogeneous disorder. The diagnosis can be
established in most cases by a general practitioner when the symptoms meet
recognized criteria and a somatic disease sufficiently explaining the symptoms is
excluded. Evidence-based interdisciplinary guidelines give a strong
recommendation for aerobic exercise and cognitive behavioral therapies. Drug
therapy is not mandatory. Only a minority of patients experience substantial
symptom relief with duloxetine, milnacipran, and pregabalin.
PMID- 29946214
TI - Psychiatric sequelae of cardiac arrest.
AB - This manuscript summarizes the literature on mental health outcomes after cardiac
arrest. Survivors of cardiac arrest show high rates of mental illness with more
than 40% suffering from anxiety, 30% from depression, and 25% from posttraumatic
stress disorder (PTSD). Mental health outcomes may differ depending on the
setting in which the cardiac arrest occurred. A major problem is reduced
neuropsychological functioning. Between 30% and 50% of survivors of cardiac
arrest suffer from cognitive deficits. Deficits of attention, declarative memory,
executive function, visual-spatial abilities, and verbal fluency have been
observed. As a result of numerous psychopathological symptoms (depression in 14%
to 45%, anxiety in 13% to 61%, and PTSD in 19% to 27%) and reduced cognitive
functioning (about 20% to 60%), relevantly reduced quality of life is observed in
about 20% of cardiac arrest survivors.
PMID- 29946213
TI - Metabolic syndrome in psychiatric patients: overview, mechanisms, and
implications.
AB - Psychiatric patients have a greater risk of premature mortality, predominantly
due to cardiovascular diseases (CVDs). Convincing evidence shows that psychiatric
conditions are characterized by an increased risk of metabolic syndrome (MetS), a
clustering of cardiovascular risk factors including dyslipidemia, abdominal
obesity, hypertension, and hyperglycemia. This increased risk is present for a
range of psychiatric conditions, including major depressive disorder (MDD),
bipolar disorder (BD), schizophrenia, anxiety disorder, attention
deficit/hyperactivity disorder (ADHD), and posttraumatic stress disorder (PTSD).
There is some evidence for a dose-response association with the severity and
duration of symptoms and for a bidirectional longitudinal impact between
psychiatric disorders and MetS. Associations generally seem stronger with
abdominal obesity and dyslipidemia dysregulations than with hypertension.
Contributing mechanisms are an unhealthy lifestyle and a poor adherence to
medical regimen, which are prevalent among psychiatric patients. Specific
psychotropic medications have also shown a profound impact in increasing MetS
dysregulations. Finally, pleiotropy in genetic vulnerability and
pathophysiological mechanisms, such as those leading to the increased central and
peripheral activation of immunometabolic or endocrine systems, plays a role in
both MetS and psychiatric disorder development. The excess risk of MetS and its
unfavorable somatic health consequences justifies a high priority for future
research, prevention, close monitoring, and treatment to reduce MetS in the
vulnerable psychiatric patient.
PMID- 29946216
TI - Angiotensin II, Oxidative Stress, and Sympathetic Nervous System Hyperactivity in
Heart Failure.
AB - In congestive heart failure (CHF), sympathetic nervous system is hyperactive.
This article reviews current understandings about central and peripheral neural
mechanisms underlying sympathetic hyperactivation in this pathological condition.
During the development of CHF, renin-angiotensin system (RAS) activities and
angiotensin II-mediated oxidative stress become enhanced. Here, on the basis of
findings obtained from animal studies, it is examined how RAS overactivation and
oxidative stress in central and peripheral nervous systems of CHF mediate
sympathetic hyperactivation. Mechanisms by which exercise training in CHF
ameliorates RAS overactivation, oxidative stress and sympathetic hyperactivation
are also investigated.
PMID- 29946215
TI - Negative Symptoms and Cognitive Impairments in Schizophrenia: Two Key Symptoms
Negatively Influencing Social Functioning.
AB - Schizophrenia is a chronic, disabling disorder, which commonly emerges in
adolescence and young adulthood. While pharmacological treatment with currently
available second-generation antipsychotics exerts beneficial effects on the
positive symptoms of schizophrenia, they have little effect on negative symptoms
or cognitive deficits. Because these two types of symptoms are enduring, and
negatively impact social functioning throughout the course of the illness, there
is an urgent requirement to develop new effective therapeutic approaches to
manage them. Negative symptoms have proven difficult to assess accurately because
of their complexity, even with commonly used clinical rating scales such as the
Scales for Assessment of Negative Symptoms (SANS). In this context, new "next
generation" assessment tools have recently been developed, which include items
representing the five domains encompassed by the two established clusters of
negative symptoms (diminished expression and avolition), and enable the detection
of changes in severity. Despite various therapeutic approaches to alleviating
negative symptoms, there are currently no established methods available for
clinical practice. Cognitive deficits are also a core feature in the majority of
people with schizophrenia, with impaired performance observed across many
cognitive domains, including verbal memory, working memory, attention, and
executive functions. Such cognitive deficits are likely associated with either
reduced or inefficient function of related distributed neural networks.
Psychosocial treatments for cognitive impairments in schizophrenia seem promising
given the beneficial effects of cognitive remediation therapy on such
impairments, as well as on social functioning, as substantiated in several meta
analytic studies with modest effect sizes. Furthermore, using functional
neuroimaging techniques, the size of these therapy-induced beneficial changes in
neurocognitive performance has been demonstrated to be correlated with the degree
of the changes in brain activation during performing some cognitive tasks in the
prefrontal and temporal cortices. This suggests neurobiological effects are
exerted by psychosocial cognitive remediation treatments.
PMID- 29946217
TI - Bilateral Ovarian Tumors on MRI: How Should We Differentiate the Lesions?
AB - Background: We investigated the distinguishing pathological features of bilateral
ovarian tumors using magnetic resonance (MR) imaging. Methods: Eighty-six
patients with bilateral ovarian tumors on MR imaging were evaluated. The
pathological diagnosis was investigated, and the results were subjected to
statistical analysis using Mann-Whitney U test, Fisher's exact test, Chi-squared
test and receiver operating characteristic (ROC) curve to determine the features
useful for the differentiation of distinct types of lesions. Results: The
diagnosis of bilateral ovarian tumors was confirmed in eighty-one patients and
the majority of the lesions were further classified into serous carcinoma (n =
36), mature teratoma (n = 20) and metastasis (n = 12). We assessed the existence
of factors useful for the MR imaging differentiation between metastasis and
serous carcinoma or primary malignant ovarian tumors. Cancer antigen (CA) 125
serum level and maximum tumor diameter were significantly different between
metastasis and serous carcinoma and similarly, between metastasis and primary
malignant ovarian tumors. MR imaging morphology, ascites and peritoneal implants
did not show any significant difference between the different types of lesions.
Conclusion: Within our patient cohort, most bilateral ovarian tumor lesions were
determined to be serous carcinoma, mature teratoma or metastasis. CA 125 serum
level and maximum tumor diameter are useful markers for the differentiation
between metastasis and serous carcinoma or primary malignant ovarian tumors.
PMID- 29946218
TI - The Utility of the Combined Use of 123I-FP-CIT and 123I-MIBG Myocardial
Scintigraphy in Differentiating Parkinson's Disease from Other Parkinsonian
Syndromes.
AB - Background: 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and 123I
FP-CIT dopamine transporter single photon emission computed tomography (DAT
SPECT) provide specific information that distinguish Parkinson's disease (PD)
from parkinsonian syndromes other than PD (non-PD), including atypical
parkinsonian disorder (APD) and non-PD other than APD (nPD-nAPD). The purpose of
this study was to determine whether combining DAT-SPECT and MIBG myocardial
scintigraphy using multiparametric scoring system (MSS) could improve diagnostic
test accuracy in discriminating PD from APD or discriminating PD from nPD-nAPD.
Methods: A total of 52 patients, including 36 PD, eight APD and eight nPD-nAPD,
underwent both MIBG myocardial scintigraphy and DAT-SPECT, were evaluated. The
heart-to-mediastinum (H/M) ratios (early and delayed), washout-rate (WR), the
average (Ave) and asymmetry index (AI) of specific binding ratio (SBR) were
calculated. Cutoff values were determined, using ROC analysis, for discriminating
PD from APD and for discriminating PD from nPD-nAPD, on five parameters. All
cases were scored as either 1 (PD) or 0 (nPD-nAPD or APD) for each parameter
according to its threshold in each discrimination. These individual scores were
summed for each case, yielding a combined score to obtain a cutoff value for the
MSS in each discrimination. Results: For discriminating PD from nPD-nAPD, the
highest accuracy was 80% at a cutoff value of 19% for the WR and a cut off value
of 2 improved diagnostic accuracy to 84% for MSS. For discriminating PD from APD,
the highest accuracy was 86% at a cutoff value of 2.8 for the H/M ratio (late)
and a cut off value of 2 showed diagnostic accuracy of 86% for MSS. Conclusion: A
MSS has comparable or better accuracy compared to each parameter of MIBG
myocardial scintigraphy and DAT-SPECT in distinguishing PD from nPD-nAPD or
distinguishing PD from APD.
PMID- 29946220
TI - Early Stage of Pilomatricoma with an Empty Cyst Cavity and Unusual Clinical
Appearance.
AB - We present an unusual case of cystic pilomatricoma. A 13-year-old Japanese boy
was referred to our department for evaluation of a 10-day history of a small
reddish nodule on his right cheek. Histopathological examination showed a well
circumscribed cystic structure showing a central empty cavity in the dermis. The
wall of the cyst was composed of basophilic cells. Inner layers of the wall were
covered with flattened epithelial cells having trichohyalin granules. Based on
these findings, a diagnosis of cystic pilomatricoma was made. To our knowledge,
there has been no report of cystic pilomatricoma with an empty cavity.
Dermatologists should be aware of pilomatricoma in the early stage showing a
central empty cavity.
PMID- 29946219
TI - Indirubin, a Constituent of the Chinese Herbal Medicine Qing-Dai, Attenuates
Dextran Sulfate Sodium-induced Murine Colitis.
AB - Background: Indirubin, a constituent of the Chinese herbal medicine "Qing-Dai,"
has anti-cancer and anti-inflammatory activities. We aimed to evaluate the
efficacy of indirubin for ameliorating colonic inflammation in a mouse model of
inflammatory bowel disease. Methods: Mice with dextran sulfate sodium (DSS)
induced acute and chronic colitis were treated with indirubin in their diet.
Clinical and histologic changes were evaluated. In addition, colon levels of
interleukin-6, a critical pro-inflammatory mediator, was detected by enzyme
linked immunosorbent assay. Results: In the model of acute colitis, indirubin
treatment improved the loss of body weight. Histology of colonic tissue revealed
that indirubin treatment improved the histology grading of colitis (P = 0.02),
the extent of submucosal fibrosis (P = 0.018), the number of mucosal toluidine
blue-positive cells (P = 0.004) and colon length (P = 0.01). In the model of
chronic colitis, indirubin treatment had no significant effect on pathologic
findings except for colon length (P = 0.003). However, indirubin administration
significantly reduced colon levels of interleukin-6 in the chronic-colitis model
(P = 0.001). Conclusion: Our study clearly showed that oral intake of indirubin
can improve murine DSS-induced colitis (which mimics human inflammatory bowel
disease).
PMID- 29946221
TI - Squamous Cell Carcinoma Manifested as a Cutaneous Horn: A Key to Early Detection.
AB - We report a case of squamous cell carcinoma manifested as a cutaneous horn. A 92
year-old man was referred to our department for evaluation of a 3-month history
of a keratotic cutaneous horn on the left side of his neck. The height of the
cutaneous horn was larger than the diameter of erythema at the base.
Histopathological examination showed a hyperkeratotic horn developing over a mass
of large atypical keratinocytes with large hyperchromatic and pleomorphic nuclei.
Based on these findings, a diagnosis of squamous cell carcinoma was made. A
recent study showed that cutaneous horns in association with invasive squamous
cell carcinoma had a tendency to have less height than the diameter of the base.
In our case, however, the height of the cutaneous horn was larger than the
diameter of the base, indicating that invasive squamous cell carcinoma sometimes
shows a cutaneous horn that is higher than the diameter of the base. Thus,
clinical finding of erythema at the base of the cutaneous horn would be a
reliable feature for early detection of squamous cell carcinoma.
PMID- 29946222
TI - Successful Surgical Remodeling of a Giant Venous Aneurysm Formed in an Autogenous
Arteriovenous Fistula: A Case Report.
AB - One complication of an autogenous arteriovenous fistula (AVF) for hemodialysis is
the formation of a venous aneurysm. The treatment of a massive aneurysmal AVF
generally involves ligation or resection with the use of prosthetic
interposition. We present the case of a 46-year-old man in whom an AVF aneurysm
was successfully treated by placating the excess free wall of the aneurysm with
sutures. This method is a simple and effective intervention for managing aneurysm
associated complications. In addition, this approach helps to maintain the
benefits of autogenous access while conserving future dialysis sites.
PMID- 29946223
TI - Interferon-gamma and Smac mimetics synergize to induce apoptosis of lung cancer
cells in a TNFalpha-independent manner.
AB - Background: The prognosis of lung cancer is very poor and hence new therapeutic
strategies are urgently desired. In this study, we searched for efficacious Smac
mimetic-based combination therapies with biomarkers to predict responses for non
small cell lung cancer (NSCLC). Methods: NSCLC cell lines and normal human
alveolar epithelial cells were treated with Smac mimetics plus IFNgamma or other
agonists and cell viabilities were assessed by MTS assay, cell counting, flow
cytometry and cell colony assay. Western blot analysis was performed to assess
the cleavage (activation) of caspases and expression of signaling molecules.
Caspase activity was determined to verify caspase activation. The pathways
involved in NSCLC cell death were investigated using specific inhibitors.
Results: We found that IFNgamma could cooperate with various Smac mimetics to
trigger a profound apoptosis in a number of NSCLC cell lines that are competent
for IFNgamma signaling (i.e. expressing IFNgamma receptor-1 and STAT1) but have
low expression levels of inhibitor of apoptosis proteins survivin and livin
without harming normal human lung epithelial cells. IFNgamma co-treatment with a
novel class dimeric Smac mimetic AZD5582 eradicated NSCLC cell colony formation.
Unlike IFNgamma, IFNalpha, IFNlambda, TNFalpha, or TRAIL alone or plus AZD5582
had minor effects on NSCLC cell viability. IFNgamma/AZD5582-induced cell death in
NSCLC cells was independent of TNFalpha autocrine but relied on apoptosis
mediated by JAK kinase, caspase 8 and RIPK1 pathways. Conclusion: Our results
indicate that IFNgamma and Smac mimetics can synergize to induce apoptosis of
NSCLC cells and suggest that IFNgamma and Smac mimetic regimen may be a novel and
efficacious apoptosis targeted therapy with biomarkers to predict responses for
NSCLC cells.
PMID- 29946224
TI - Targeting dendritic cells in pancreatic ductal adenocarcinoma.
AB - Dendritic cells (DC) are an integral part of the tumor microenvironment.
Pancreatic cancer is characterized by reduced number and function of DCs, which
impacts antigen presentation and contributes to immune tolerance. Recent data
suggest that exosomes can mediate communication between pancreatic cancer cells
and DCs. Furthermore, levels of DCs may serve as prognostic factors. There is
also growing evidence for the effectiveness of vaccination with DCs pulsed with
tumor antigens to initiate adaptive cytolytic immune responses via T cells. Most
experience with DC-based vaccination has been gathered for MUC1 and WT1 antigens,
where clinical studies in advanced pancreatic cancer have provided encouraging
results. In this review, we highlight the role of DC in the course, prognosis and
treatment of pancreatic cancer.
PMID- 29946225
TI - House dust mite-related respiratory allergies and probiotics: a narrative review.
AB - The socio-economic burden of allergic respiratory conditions on continental
Europe is even higher than that of mainstream diseases, such as diabetes and
cardiovascular disease, as allergic rhinitis alone accounts for billions of Euros
in healthcare expenses across Europe. House dust mites (HDM) are one of the most
common triggers behind allergic rhinitis and asthma. The role of probiotics in
the treatment and prevention of some allergic conditions, such as atopic
dermatitis, is already well recognized, whereas evidence about their efficacy in
patients with respiratory allergies-while increasing-is still limited. Here the
current evidence for the use of probiotics in patients with allergic rhinitis
and/or asthma is discussed.
PMID- 29946226
TI - Experimental murine acute lung injury induces increase of pulmonary TIE2
expressing macrophages.
AB - Background: Breakdown of the alveolo-capillary wall is pathognomonic for Acute
Lung Injury (ALI). Angiopoietins, vascular-specific growth factors, are linked to
endothelial barrier dysfunction, and elevated Angiopoietin-2 (ANG2) levels are
associated with poor outcome of ALI patients. Specialized immune cells, referred
to as 'TIE2-expressing monocytes and macrophages' (TEM), were shown to
specifically respond to ANG2 binding. However, their involvement in acute
inflammatory processes is so far completely undescribed. Thus, our aim was to
assess the dynamics of TEMs in a murine model of ALI. Results: Intratracheal
instillation of LPS induced a robust pulmonary pro-inflammatory response with
endothelial barrier dysfunction and significantly enhanced ANG2 expression. The
percentage number of TEMs, assessed by FACS analysis, was more than trebled
compared to controls, with TEM count in lungs reaching more than 40% of all
macrophages. Such distinct dynamic was absent in all other analyzed compartments
(alveolar space, spleen, blood). Incubation of the monocytic cell line THP-1 with
LPS or TNF-alpha resulted in a dose-dependent, significant upregulation of TIE2,
suggesting that not recruitment from extra-pulmonary compartments but TIE2
upregulation in resident macrophages accounts for increased lung TEM frequencies.
Conclusions: For the first time, our data provide evidence that the activity of
TEMs changes at sites of acute inflammation.
PMID- 29946227
TI - Activated protein C plays no major roles in the inhibition of coagulation or
increased fibrinolysis in acute coagulopathy of trauma-shock: a systematic
review.
AB - Background: The pathophysiological mechanisms of acute coagulopathy of trauma
shock (ACOTS) are reported to include activated protein C-mediated suppression of
thrombin generation via the proteolytic inactivation of activated Factor V (FVa)
and FVIIIa; an increased fibrinolysis via neutralization of plasminogen activator
inhibitor-1 (PAI-1) by activated protein C. The aims of this study are to review
the evidences for the role of activated protein C in thrombin generation and
fibrinolysis and to validate the diagnosis of ACOTS based on the activated
protein C dynamics. Methods: We conducted systematic literature search (2007
2017) using PubMed, the Cochrane Database of Systematic Reviews (CDSR), and the
Cochrane Central Register of Controlled Trials (CENTRAL). Clinical studies on
trauma that measured activated protein C or the circulating levels of activated
protein C-related coagulation and fibrinolysis markers were included in our
study. Results: Out of 7613 studies, 17 clinical studies met the inclusion
criteria. The levels of activated protein C in ACOTS were inconsistently
decreased, showed no change, or were increased in comparison to the control
groups. Irrespective of the activated protein C levels, thrombin generation was
always preserved or highly elevated. There was no report on the activated protein
C-mediated neutralization of PAI-1 with increased fibrinolysis. No included
studies used unified diagnostic criteria to diagnose ACOTS and those studies also
used different terms to refer to the condition known as ACOTS. Conclusions: None
of the studies showed direct cause and effect relationships between activated
protein C and the suppression of coagulation and increased fibrinolysis. No
definitive diagnostic criteria or unified terminology have been established for
ACOTS based on the activated protein C dynamics.
PMID- 29946228
TI - The early economic evaluation of novel biomarkers to accelerate their translation
into clinical applications.
AB - Background: Translating prognostic and diagnostic biomarker candidates into
clinical applications takes time, is very costly, and many candidates fail. It is
therefore crucial to be able to select those biomarker candidates that have the
highest chance of successfully being adopted in the clinic. This requires an
early estimate of the potential clinical impact and commercial value. In this
paper, we aim to demonstratively evaluate a set of novel biomarkers in terms of
clinical impact and commercial value, using occurrence of cardiovascular disease
(CVD) in type-2 diabetes (DM2) patients as a case study. Methods: We defined a
clinical application for the novel biomarkers, and subsequently used data from a
large cohort study in The Netherlands in a modeling exercise to assess the
potential clinical impact and headroom for the biomarkers. Results: The most
likely application of the biomarkers would be to identify DM2 patients with a low
CVD risk and subsequently withhold statin treatment. As a result, one additional
CVD event in every 75 patients may be expected. The expected downstream savings
resulted in a headroom for a point-of-care device ranging from ?119.09 at a
willingness to accept of ?0 for one additional CVD event, to ?0 at a willingness
to accept of ?15,614 or more. Conclusion: It is feasible to evaluate novel
biomarkers on outcomes directly relevant to technological development and
clinical adoption. Importantly, this may be attained at the same point in time
and using the same data as used for the evaluation of association with disease
and predictive power.
PMID- 29946229
TI - Brief interventions to address substance use among patients presenting to
emergency departments in resource poor settings: a cost-effectiveness analysis.
AB - Background: There are limited data describing the cost-effectiveness of brief
interventions for substance use in resource-poor settings. Using a patient and
provider perspective, this study investigates the cost-effectiveness of a brief
motivational interviewing (MI) intervention versus a combined intervention of MI
and problem solving therapy (MI-PST) for reducing substance use among patients
presenting to emergency departments, in comparison to a control group. Methods:
Effectiveness data were extracted from Project STRIVE (Substance use and Trauma
InterVention) conducted in South Africa. Patients were randomised to either
receive 1 session of MI (n = 113) or MI in addition to four sessions of PST (n =
109) or no intervention [control (n = 110)]. Costs included the direct health
care costs associated with the interventions. Patient costs included out of
pocket payments incurred accessing the MI-PST intervention. Outcome measures were
patients' scores on the Alcohol, Smoking and Substance Use Involvement Screening
Test (ASSIST) and the Centre for Epidemiological Studies Depression Scale (CES
D). Results: Cost per patient was low in all three groups; US$16, US$33 and
US$11, and for MI, MI-PST and control respectively. Outcomes were 0.92 (MI), 1.06
(MI-PST) and 0.88 (control) for ASSIST scores; and 0.74 (MI), 1.27 (MI-PST) and
0.53 (control) for CES-D scores. In comparison to the control group, the MI
intervention costs an additional US$119 per unit reduction in ASSIST score,
(US$20 for CES-D); MI-PST in comparison to MI costs US$131 or US$33 per unit
reduction in ASSIST or CES-D scores respectively. The sensitivity analyses showed
that increasing the number of patients who screened positive and thus received
the intervention could improve the effectiveness and cost-effectiveness of the
interventions. Conclusion: MI or MI-PST interventions delivered by lay
counsellors have the potential to be cost-effective strategies for the reduction
of substance use disorder and depressive symptoms among patients presenting at
emergency departments in resource poor settings. Given the high economic, social
and health care cost of substance use disorders in South Africa, these results
suggest that these interventions should be carefully considered for future
implementation.Trial registration This study is part of a trial registered with
the Pan African Clinical Trial Registry (PACTR201308000591418).
PMID- 29946231
TI - Complexity Analysis of Iterative Basis Transformations Applied to Event-Based
Signals.
AB - This paper introduces an event-based methodology to perform arbitrary linear
basis transformations that encompass a broad range of practically important
signal transforms, such as the discrete Fourier transform (DFT) and the discrete
wavelet transform (DWT). We present a complexity analysis of the proposed method,
and show that the amount of required multiply-and-accumulate operations is
reduced in comparison to frame-based method in natural video sequences, when the
required temporal resolution is high enough. Experimental results on natural
video sequences acquired by the asynchronous time-based neuromorphic image sensor
(ATIS) are provided to support the feasibility of the method, and to illustrate
the gain in computation resources.
PMID- 29946230
TI - Quantitative phosphoproteomic analysis reveals reciprocal activation of receptor
tyrosine kinases between cancer epithelial cells and stromal fibroblasts.
AB - Background: Cancer-associated fibroblasts (CAFs) are one of the most important
components of tumor stroma and play a key role in modulating tumor growth.
However, a mechanistic understanding of how CAFs communicate with tumor cells to
promote their proliferation and invasion is far from complete. A major reason for
this is that most current techniques and model systems do not capture the
complexity of signal transduction that occurs between CAFs and tumor cells.
Methods: In this study, we employed a stable isotope labeling with amino acids in
cell culture (SILAC) strategy to label invasive breast cancer cells, MDA-MB-231,
and breast cancer patient-derived CAF this has already been defined above cells.
We used an antibody-based phosphotyrosine peptide enrichment method coupled to LC
MS/MS to catalog and quantify tyrosine phosphorylation-mediated signal
transduction events induced by the bidirectional communication between patient
derived CAFs and tumor cells. Results: We discovered that distinct signaling
events were activated in CAFs and in tumor epithelial cells during the crosstalk
between these two cell types. We identified reciprocal activation of a number of
receptor tyrosine kinases including EGFR, FGFR1 and EPHA2 induced by this
bidirectional communication. Conclusions: Our study not only provides insights
into the mechanisms of the interaction between CAFs and tumor cells, but the
model system described here could be used as a prototype for analysis of
intercellular communication in many different tumor microenvironments.
PMID- 29946232
TI - Editorial: Limbic-Brainstem Roles in Perception, Cognition, Emotion, and
Behavior.
PMID- 29946233
TI - Repeated Administration of D-Amphetamine Induces Distinct Alterations in Behavior
and Metabolite Levels in 129Sv and Bl6 Mouse Strains.
AB - The main goal of the study was to characterize the behavioral and metabolomic
profiles of repeated administration (for 11 days) of d-amphetamine (AMPH, 3 mg/kg
i. p.), indirect agonist of dopamine (DA), in widely used 129S6/SvEvTac (129Sv)
and C57BL/6NTac (Bl6) mouse strains. Acute administration of AMPH (acute AMPH)
induced significantly stronger motor stimulation in Bl6. However, repeated
administration of AMPH (repeated AMPH) caused stronger motor sensitization in
129Sv compared acute AMPH. Body weight of 129Sv was reduced after repeated saline
and AMPH, whereas no change occurred in Bl6. In the metabolomic study, acute AMPH
induced an elevation of isoleucine and leucine, branched chain amino acids
(BCAA), whereas the level of hexoses was reduced in Bl6. Both BCAAs and hexoses
remained on level of acute AMPH after repeated AMPH in Bl6. Three biogenic amines
[asymmetric dimethylarginine (ADMA), alpha-aminoadipic acid (alpha-AAA),
kynurenine] were significantly reduced after repeated AMPH. Acute AMPH caused in
129Sv a significant reduction of valine, lysophosphatidylcholines (lysoPC a
C16:0, lysoPC a C18:2, lysoPC a C20:4), phosphatidylcholine (PC) diacyls (PC aa
C34:2, PC aa C36:2, PC aa C36:3, PC aa C36:4) and alkyl-acyls (PC ae C38:4, PC ae
C40:4). However, repeated AMPH increased the levels of valine and isoleucine,
long-chain acylcarnitines (C14, C14:1-OH, C16, C18:1), PC diacyls (PC aa C38:4,
PC aa C38:6, PC aa C42:6), PC acyl-alkyls (PC ae C38:4, PC ae C40:4, PC ae C40:5,
PC ae C40:6, PC ae C42:1, PC ae C42:3) and sphingolipids [SM(OH)C22:1, SM C24:0]
compared to acute AMPH in 129Sv. Hexoses and kynurenine were reduced after
repeated AMPH compared to saline in 129Sv. The established changes probably
reflect a shift in energy metabolism toward lipid molecules in 129Sv because of
reduced level of hexoses. Pooled data from both strains showed that the elevation
of isoleucine and leucine was a prominent biomarker of AMPH-induced behavioral
sensitization. Simultaneously a significant decline of hexoses, citrulline, ADMA,
and kynurenine occurred. The reduced levels of kynurenine, ADMA, and citrulline
likely reflect altered function of N-methyl-D-aspartate (NMDA) and NO systems
caused by repeated AMPH. Altogether, 129Sv strain displays stronger sensitization
toward AMPH and larger variance in metabolite levels than Bl6.
PMID- 29946234
TI - Variability and Predictors of Response to Continuous Theta Burst Stimulation: A
TMS-EEG Study.
AB - Continuous theta-burst stimulation (cTBS) is a repetitive transcranial magnetic
stimulation paradigm reported to decrease the excitability of the stimulated
cortical area and which is thought to reflect a form of inhibitory synaptic
plasticity. However, since its introduction, the effect of cTBS has shown a
remarkable variability in its effects, which are often quantified by measuring
the amplitude of motor evoked potentials (MEPs). Part of this inconsistency in
experimental results might be due to an intrinsic variability of TMS effects
caused by genetic or neurophysiologic factors. However, it is also possible that
MEP only reflect the excitability of a sub-population of output neurons; resting
EEG power and measures combining TMS and electroencephalography (TMS-EEG) might
represent a more thorough reflection of cortical excitability. The aim of the
present study was to verify the robustness of several predictors of cTBS
response, such as I wave recruitment and baseline MEP amplitude, and to test cTBS
after-effects on multiple neurophysiologic measurements such as MEP, resting EEG
power, local mean field power (LMFP), TMS-related spectral perturbation (TRSP),
and inter-trial phase clustering (ITPC). As a result, we were not able to confirm
either the expected decrease of MEP amplitude after cTBS or the ability of I wave
recruitment and MEP amplitude to predict the response to cTBS. Resting EEG power,
LMFP, TRSP, and ITPC showed a more consistent trend toward a decrease after cTBS.
Overall, our data suggest that the effect of cTBS on corticospinal excitability
is variable and difficult to predict with common electrophysiologic markers,
while its effect might be clearer when probed with combined TMS and EEG.
PMID- 29946235
TI - Corrigendum: Feature Selection Methods for Robust Decoding of Finger Movements in
a Non-human Primate.
AB - [This corrects the article on p. 22 in vol. 12, PMID: 29467602.].
PMID- 29946236
TI - Electro-Acupuncture Alleviates Chronic Unpredictable Stress-Induced Depressive-
and Anxiety-Like Behavior and Hippocampal Neuroinflammation in Rat Model of
Depression.
AB - Depression is the second leading cause of disability worldwide. The effects of
clinical depression may be mediated by neuroinflammation such as activation of
microglia and high levels of proinflammatory cytokines in certain brain areas.
Traditional Chinese medicine techniques such as electro-acupuncture (EA) are used
extensively in Asia to treat mental health disorders. However, EA has not been
rigorously studied in treatment of depression. This study was designed to assess
the effectiveness of EA on depressive-like behavior and explore the role of
hippocampal neuroinflammation in the potential antidepressant effect of EA. In
this study, we used six chronic unpredictable stressors daily in a random
sequence for 10 weeks. EA were performed on "Bai-Hui" (Du-20) (+) and "Yang-Ling
Quan" (GB-34, the right side; -) acupoints by an EA apparatus (HANS Electronic
Apparatus, LH202H, 2/100 Hz, 0.3 mA) for 30 min once every other day for last 4
weeks. The behavior tests including open field test and forced swimming test,
which are widely used to assess depressive and anxiety-like behavior were
performed on the Monday and Tuesday of the eleventh week. The results showed that
10 week of chronic unpredictable stress (CUS) caused behavioral deficits in rats
and neuroinflammation in hippocampus, such as increased expression of NLRP3
inflammasome components, upregulated mRNA level of IL-1beta and the protein level
of IL-1beta mature form (p17) and activation of microglia. Moreover, 4 weeks of
EA treatment significantly attenuated behavioral deficits caused by CUS. EA's
antidepressant effect was accompanied by markedly decreased expression of certain
NLRP3 inflammasome components and matured IL-1beta. Meanwhile, EA treatment can
significantly reverse CUS-induced increases in P2X7 receptor, Iba-1, IL-18,
TNFalpha and IL-6 expression and decreases in GFAP expression. In conclusion, EA
exhibited the antidepressant effect and alleviated the hippocampal
neuroinflammation. These findings may provide insight into the role of
hippocampal neuroinflammation in the antidepressant effect of EA.
PMID- 29946237
TI - The 3'UTRs of Myelin Basic Protein mRNAs Regulate Transport, Local Translation
and Sensitivity to Neuronal Activity in Zebrafish.
AB - Formation of functional myelin sheaths within the central nervous system depends
on expression of myelin basic protein (MBP). Following process extension and
wrapping around axonal segments, this highly basic protein is required for
compaction of the multi-layered membrane sheath produced by oligodendrocytes. MBP
is hypothesized to be targeted to the membrane sheath by mRNA transport and local
translation, which ensures that its expression is temporally and spatially
restricted. The mechanistic details of how this might be regulated are still
largely unknown, in particular because a model system that allows this process to
be studied in vivo is lacking. We here show that the expression of the zebrafish
MBP orthologs, mbpa and mbpb, is developmentally regulated, and that expression
of specific mbpa isoforms is restricted to the peripheral nervous system. By
analysis of transgenic zebrafish, which express a fluorescent reporter protein
specifically in myelinating oligodendrocytes, we demonstrate that both mbpa and
mbpb include a 3'UTR sequence, by which mRNA transport and translation is
regulated in vivo. Further functional analysis suggests that: (1) the 3'UTRs
delay the onset of protein expression; and that (2) several regulatory elements
contribute to targeting of the mbp mRNA to the myelin sheath. Finally, we show
that a pharmacological compound known to enhance neuronal activity stimulates the
translation of Mbp in zebrafish in a 3'UTR-dependent manner. A similar effect was
obtained following stimulation with a TrkB receptor agonist, and cell-based
assays further confirmed that the receptor ligand, BDNF, in combination with
other signals reversed the inhibitory effect of the 3'UTR on translation.
PMID- 29946239
TI - BDNF-TrkB Signaling Coupled to nPKCepsilon and cPKCbetaI Modulate the
Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at
the Neuromuscular Junction.
AB - Munc18-1, a neuron-specific member of the Sec1/Munc18 family, is involved in
neurotransmitter release by binding tightly to syntaxin. Munc18-1 is
phosphorylated by PKC on Ser-306 and Ser-313 in vitro which reduces the amount of
Munc18-1 able to bind syntaxin. We have previously identified that PKC is
involved in neurotransmitter release when continuous electrical stimulation
imposes a moderate activity on the NMJ and that muscle contraction through TrkB
has an important impact on presynaptic PKC isoforms levels, specifically
cPKCbetaI and nPKCepsilon. Therefore, the present study was designed to
understand how Munc18-1 phosphorylation is affected by (1) synaptic activity at
the neuromuscular junction, (2) nPKCepsilon and cPKCbetaI isoforms activity, (3)
muscle contraction per se, and (4) the BDNF/TrkB signaling in a neuromuscular
activity-dependent manner. We performed immunohistochemistry and confocal
techniques to evidence the presynaptic location of Munc18-1 in the rat diaphragm
muscle. To study synaptic activity, we stimulated the phrenic nerve (1 Hz, 30
min) with or without contraction (abolished by MU-conotoxin GIIIB). Specific
inhibitory reagents were used to block nPKCepsilon and cPKCbetaI activity and to
modulate the tropomyosin receptor kinase B (TrkB). Main results obtained from
Western blot experiments showed that phosphorylation of Munc18-1 at Ser-313
increases in response to a signaling mechanism initiated by synaptic activity and
directly mediated by nPKCepsilon. Otherwise, cPKCbetaI and TrkB activities work
together to prevent this synaptic activity-induced Munc18-1 phosphorylation by a
negative regulation of cPKCbetaI over nPKCepsilon. Therefore, a balance between
the activities of these PKC isoforms could be a relevant cue in the regulation of
the exocytotic apparatus. The results also demonstrate that muscle contraction
prevents the synaptic activity-induced Munc18-1 phosphorylation through a
mechanism that opposes the TrkB/cPKCbetaI/nPKCepsilon signaling.
PMID- 29946238
TI - Astroglial Modulation of Hydromineral Balance and Cerebral Edema.
AB - Maintenance of hydromineral balance (HB) is an essential condition for life
activity at cellular, tissue, organ and system levels. This activity has been
considered as a function of the osmotic regulatory system that focuses on
hypothalamic vasopressin (VP) neurons, which can reflexively release VP into the
brain and blood to meet the demand of HB. Recently, astrocytes have emerged as an
essential component of the osmotic regulatory system in addition to functioning
as a regulator of the HB at cellular and tissue levels. Astrocytes express all
the components of osmoreceptors, including aquaporins, molecules of the
extracellular matrix, integrins and transient receptor potential channels, with
an operational dynamic range allowing them to detect and respond to osmotic
changes, perhaps more efficiently than neurons. The resultant responses, i.e.,
astroglial morphological and functional plasticity in the supraoptic and
paraventricular nuclei, can be conveyed, physically and chemically, to adjacent
VP neurons, thereby influencing HB at the system level. In addition, astrocytes,
particularly those in the circumventricular organs, are involved not only in VP
mediated osmotic regulation, but also in regulation of other osmolality
modulating hormones, including natriuretic peptides and angiotensin. Thus,
astrocytes play a role in local/brain and systemic HB. The adaptive astrocytic
reactions to osmotic challenges are associated with signaling events related to
the expression of glial fibrillary acidic protein and aquaporin 4 to promote cell
survival and repair. However, prolonged osmotic stress can initiate inflammatory
and apoptotic signaling processes, leading to glial dysfunction and a variety of
brain diseases. Among many diseases of brain injury and hydromineral disorders,
cytotoxic and osmotic cerebral edemas are the most common pathological
manifestation. Hyponatremia is the most common cause of osmotic cerebral edema.
Overly fast correction of hyponatremia could lead to central pontine
myelinolysis. Ischemic stroke exemplifies cytotoxic cerebral edema. In this
review, we summarize and analyze the osmosensory functions of astrocytes and
their implications in cerebral edema.
PMID- 29946240
TI - Adeno-Associated Viral Vector Serotype DJ-Mediated Overexpression of N171-82Q
Mutant Huntingtin in the Striatum of Juvenile Mice Is a New Model for
Huntington's Disease.
AB - Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative
disorder characterized by motor, psychiatric and cognitive symptoms. HD is caused
by an expansion of CAG repeats in the huntingtin (HTT) gene in various areas of
the brain including striatum. There are few suitable animal models to study the
pathogenesis of HD and validate therapeutic strategies. Recombinant adeno
associated viral (AAV) vectors successfully transfer foreign genes to the brain
of adult mammalians. In this article, we report a novel mouse model of HD
generated by bilateral intrastriatal injection of AAV vector serotype DJ (AAV-DJ)
containing N171-82Q mutant HTT (82Q) and N171-18Q wild type HTT (18Q; sham). The
AAV-DJ-82Q model displayed motor dysfunctions in pole and rotarod tests beginning
4 weeks after viral infection in juvenile mice (8 weeks after birth). They showed
behaviors reflecting neurodegeneration. They also showed increased apoptosis,
robust glial activation and upregulated representative inflammatory cytokines
(tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6), mediators
(cyclooxygenase-2 and inducible nitric oxide synthase) and signaling pathways
(nuclear factor kappa B and signal transducer and activator of transcription 3
(STAT3)) in the striatum at 10 weeks after viral infection (14 weeks after birth)
via successful transfection of mutant HTT into neurons, microglia, and astrocytes
in the striatum. However, little evidence of any of these events was found in
mice infected with the AAV-DJ-18Q expressing construct. Intrastriatal injection
of AAV-DJ-82Q might be useful as a novel in vivo model to investigate the biology
of truncated N-terminal fragment (N171) in the striatum and to explore the
efficacy of therapeutic strategies for HD.
PMID- 29946242
TI - Space Balls Revisited: Stereological Estimates of Length With Virtual Isotropic
Surface Probes.
AB - The space ball probe was fully described in the literature 15 years ago by Mouton
et al. (2002). Since then, it has been used in a number of studies in the nervous
system that focus on axon, dendrite, and capillary length. The length of
structural parameters in tissues reflect functional aspects of the tissues. Here,
some of the various applications of this methodology will be presented, along
with a review of the salient features of the methodology that has resulted in new
wave of quantitative morphological studies of length in the nervous system. The
validity of the method is discussed in view of its widespread use along with
insights into the problems associated with its application to histological tissue
and future techniques for applying space balls.
PMID- 29946241
TI - Cell Specific Changes of Autophagy in a Mouse Model of Contusive Spinal Cord
Injury.
AB - Autophagy is an essential process of cellular waist clearance that becomes
altered following spinal cord injury (SCI). Details on these changes, including
timing after injury, underlying mechanisms, and affected cells, remain
controversial. Here we present a characterization of autophagy in the mice spinal
cord before and after a contusive SCI. In the undamaged spinal cord, analysis of
LC3 and Beclin 1 autophagic markers reveals important differences in basal
autophagy between neurons, oligodendrocytes, and astrocytes and even within cell
populations. Following moderate contusion, western blot analyses of LC3 indicates
that autophagy increases to a maximum at 7 days post injury (dpi), whereas
unaltered Beclin 1 expression and increase of p62 suggests a possible blockage of
autophagosome clearance. Immunofluorescence analyses of LC3 and Beclin 1 provide
additional details that reveal a complex, cell-specific scenario. Autophagy is
first activated (1 dpi) in the severed axons, followed by a later (7 dpi)
accumulation of phagophores and/or autophagosomes in the neuronal soma without
signs of increased initiation. Oligodendrocytes and reactive astrocytes also
accumulate phagophores and autophagosomes at 7 dpi, but whereas the accumulation
in astrocytes is associated with an increased autophagy initiation, it seems to
result from a blockage of the autophagic flux in oligodendrocytes. Comparison
with previous studies highlights the complex and heterogeneous autophagic
responses induced by the SCI, leading in many cases to contradictory results and
interpretations. Future studies should consider this complexity in the design of
therapeutic interventions based on the modulation of autophagy to treat SCI.
PMID- 29946243
TI - Reciprocal Interactions Between Gut Microbiota and Host Social Behavior.
AB - Animals harbor an extensive, dynamic microbial ecosystem in their gut. Gut
microbiota (GM) supposedly modulate various host functions including fecundity,
metabolism, immunity, cognition and behavior. Starting by analyzing the concept
of the holobiont as a unit of selection, we highlight recent findings suggesting
an intimate link between GM and animal social behavior. We consider two
reciprocal emerging themes: (i) that GM influence host social behavior; and (ii)
that social behavior and social structure shape the composition of the GM across
individuals. We propose that, throughout a long history of coevolution, GM may
have become involved in the modulation of their host's sociality to foster their
own transmission, while in turn social organization may have fine-tuned the
transmission of beneficial endosymbionts and prevented pathogen infection. We
suggest that investigating these reciprocal interactions can advance our
understanding of sociality, from healthy and impaired social cognition to the
evolution of specific social behaviors and societal structure.
PMID- 29946244
TI - Functional Connectivity and Genetic Profile of a "Double-Cortex"-Like
Malformation.
AB - Laminar heterotopia is a rare condition consisting in an extra layer of gray
matter under properly migrated cortex; it configures an atypical presentation of
periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We
conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy
patient with "double-cortex"-like malformation to reveal her functional
connectivity (FC) as well as a wide genetic analysis to identify possible genetic
substrates. Heterotopias were segmented into region of interests (ROIs), whose
voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii)
its contralateral homologous, and (iii) those of 30 age-matched healthy controls.
Extensive genetic analysis was conducted to screen cortical malformations
associated genes. Compared to healthy controls, both laminar heterotopias and the
overlying cortex showed significant reduction of FC with the contralateral
hemisphere. Two heterozygous variants of uncertain clinical significance were
found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1.
This first FC analysis of a unique case of "double-cortex"-like malformation
revealed a hemispheric connectivity segregation both in the laminar cortex as in
the correctly migrated one, with a new pattern of genes' mutations. Our study
suggests the altered FC could have an electrophysiological and functional impact
on large-scale brain networks, and the involvement of not yet identified genes in
"double-cortex"-like malformation with a possible role of rare variants in
recessive genes as pathogenic cofactors.
PMID- 29946245
TI - Tactile-to-Visual Cross-Modal Transfer of Texture Categorisation Following
Training: An fMRI Study.
AB - We investigated the neural underpinnings of texture categorisation using
exemplars that were previously learned either within modalities (visual training
and visual test) or across modalities (tactile training and visual test).
Previous models of learning suggest a decrease in activation in brain regions
that are typically involved in cognitive control during task acquisition, but a
concomitant increase in activation in brain regions associated with the
representation of the acquired information. In our study, participants were
required to learn to categorise fabrics of different textures as either natural
or synthetic. Training occurred over several sessions, with each fabric presented
either visually or through touch to a participant. Pre- and post-training tests,
in which participants categorised visual images only of the fabrics, were
conducted during a functional magnetic resonance imaging (fMRI) scan. Consistent
with previous research on cognitive processes involved in task acquisition, we
found that categorisation training was associated with a decrease in activation
in brain regions associated with cognitive systems involved in learning,
including the superior parietal cortex, dorsal anterior cingulate cortex (dACC),
and the right dorsolateral prefrontal cortex (DLFC). Moreover, these decreases
were independent of training modality. In contrast, we found greater activation
to visual textures in a region within the left medial occipital cortex (MOC)
following training. There was no overall evidence of an effect of training
modality in the main analyses, with texture-specific regional changes associated
with both within- (visual) and cross- (touch) modal training. However, further
analyses suggested that, unlike categorisation performance following within-modal
training, crossmodal training was associated with bilateral activation of the
MOC. Our results support previous evidence for a multisensory representation of
texture within early visual regions of the cortex and provide insight into how
multisensory categories are formed in the brain.
PMID- 29946247
TI - Dynamic Facial Expressions Prime the Processing of Emotional Prosody.
AB - Evidence suggests that emotion is represented supramodally in the human brain.
Emotional facial expressions, which often precede vocally expressed emotion in
real life, can modulate event-related potentials (N100 and P200) during emotional
prosody processing. To investigate these cross-modal emotional interactions, two
lines of research have been put forward: cross-modal integration and cross-modal
priming. In cross-modal integration studies, visual and auditory channels are
temporally aligned, while in priming studies they are presented consecutively.
Here we used cross-modal emotional priming to study the interaction of dynamic
visual and auditory emotional information. Specifically, we presented dynamic
facial expressions (angry, happy, neutral) as primes and emotionally-intoned
pseudo-speech sentences (angry, happy) as targets. We were interested in how
prime-target congruency would affect early auditory event-related potentials,
i.e., N100 and P200, in order to shed more light on how dynamic facial
information is used in cross-modal emotional prediction. Results showed enhanced
N100 amplitudes for incongruently primed compared to congruently and neutrally
primed emotional prosody, while the latter two conditions did not significantly
differ. However, N100 peak latency was significantly delayed in the neutral
condition compared to the other two conditions. Source reconstruction revealed
that the right parahippocampal gyrus was activated in incongruent compared to
congruent trials in the N100 time window. No significant ERP effects were
observed in the P200 range. Our results indicate that dynamic facial expressions
influence vocal emotion processing at an early point in time, and that an
emotional mismatch between a facial expression and its ensuing vocal emotional
signal induces additional processing costs in the brain, potentially because the
cross-modal emotional prediction mechanism is violated in case of emotional prime
target incongruency.
PMID- 29946246
TI - Disruption of Boundary Encoding During Sensorimotor Sequence Learning: An MEG
Study.
AB - Music performance relies on the ability to learn and execute actions and their
associated sounds. The process of learning these auditory-motor contingencies
depends on the proper encoding of the serial order of the actions and sounds.
Among the different serial positions of a behavioral sequence, the first and last
(boundary) elements are particularly relevant. Animal and patient studies have
demonstrated a specific neural representation for boundary elements in prefrontal
cortical regions and in the basal ganglia, highlighting the relevance of their
proper encoding. The neural mechanisms underlying the encoding of sequence
boundaries in the general human population remain, however, largely unknown. In
this study, we examined how alterations of auditory feedback, introduced at
different ordinal positions (boundary or within-sequence element), affect the
neural and behavioral responses during sensorimotor sequence learning. Analysing
the neuromagnetic signals from 20 participants while they performed short piano
sequences under the occasional effect of altered feedback (AF), we found that at
around 150-200 ms post-keystroke, the neural activities in the dorsolateral
prefrontal cortex (DLPFC) and supplementary motor area (SMA) were dissociated for
boundary and within-sequence elements. Furthermore, the behavioral data
demonstrated that feedback alterations on boundaries led to greater performance
costs, such as more errors in the subsequent keystrokes. These findings jointly
support the idea that the proper encoding of boundaries is critical in acquiring
sensorimotor sequences. They also provide evidence for the involvement of a
distinct neural circuitry in humans including prefrontal and higher-order motor
areas during the encoding of the different classes of serial order.
PMID- 29946248
TI - Improving the Nulling Beamformer Using Subspace Suppression.
AB - Magnetoencephalography (MEG) captures the magnetic fields generated by neuronal
current sources with sensors outside the head. In MEG analysis these current
sources are estimated from the measured data to identify the locations and time
courses of neural activity. Since there is no unique solution to this so-called
inverse problem, multiple source estimation techniques have been developed. The
nulling beamformer (NB), a modified form of the linearly constrained minimum
variance (LCMV) beamformer, is specifically used in the process of inferring
interregional interactions and is designed to eliminate shared signal
contributions, or cross-talk, between regions of interest (ROIs) that would
otherwise interfere with the connectivity analyses. The nulling beamformer
applies the truncated singular value decomposition (TSVD) to remove small signal
contributions from a ROI to the sensor signals. However, ROIs with strong
crosstalk will have high separating power in the weaker components, which may be
removed by the TSVD operation. To address this issue we propose a new method, the
nulling beamformer with subspace suppression (NBSS). This method, controlled by a
tuning parameter, reweights the singular values of the gain matrix mapping from
source to sensor space such that components with high overlap are reduced. By
doing so, we are able to measure signals between nearby source locations with
limited cross-talk interference, allowing for reliable cortical connectivity
analysis between them. In two simulations, we demonstrated that NBSS reduces
cross-talk while retaining ROIs' signal power, and has higher separating power
than both the minimum norm estimate (MNE) and the nulling beamformer without
subspace suppression. We also showed that NBSS successfully localized the
auditory M100 event-related field in primary auditory cortex, measured from a
subject undergoing an auditory localizer task, and suppressed cross-talk in a
nearby region in the superior temporal sulcus.
PMID- 29946249
TI - A Retinotopic Spiking Neural Network System for Accurate Recognition of Moving
Objects Using NeuCube and Dynamic Vision Sensors.
AB - This paper introduces a new system for dynamic visual recognition that combines
bio-inspired hardware with a brain-like spiking neural network. The system is
designed to take data from a dynamic vision sensor (DVS) that simulates the
functioning of the human retina by producing an address event output (spike
trains) based on the movement of objects. The system then convolutes the spike
trains and feeds them into a brain-like spiking neural network, called NeuCube,
which is organized in a three-dimensional manner, representing the organization
of the primary visual cortex. Spatio-temporal patterns of the data are learned
during a deep unsupervised learning stage, using spike-timing-dependent
plasticity. In a second stage, supervised learning is performed to train the
network for classification tasks. The convolution algorithm and the mapping into
the network mimic the function of retinal ganglion cells and the retinotopic
organization of the visual cortex. The NeuCube architecture can be used to
visualize the deep connectivity inside the network before, during, and after
training and thereby allows for a better understanding of the learning processes.
The method was tested on the benchmark MNIST-DVS dataset and achieved a
classification accuracy of 92.90%. The paper discusses advantages and limitations
of the new method and concludes that it is worth exploring further on different
datasets, aiming for advances in dynamic computer vision and multimodal systems
that integrate visual, aural, tactile, and other kinds of information in a
biologically plausible way.
PMID- 29946250
TI - Effects of Adaptation on Discrimination of Whisker Deflection Velocity and
Angular Direction in a Model of the Barrel Cortex.
AB - Two important stimulus features represented within the rodent barrel cortex are
velocity and angular direction of whisker deflection. Each cortical barrel
receives information from thalamocortical (TC) cells that relay information from
a single whisker, and TC input is decoded by barrel regular-spiking (RS) cells
through a feedforward inhibitory architecture (with inhibition delivered by
cortical fast-spiking or FS cells). TC cells encode deflection velocity through
population synchrony, while deflection direction is encoded through the
distribution of spike counts across the TC population. Barrel RS cells encode
both deflection direction and velocity with spike rate, and are divided into
functional domains by direction preference. Following repetitive whisker
stimulation, system adaptation causes a weakening of synaptic inputs to RS cells
and diminishes RS cell spike responses, though evidence suggests that stimulus
discrimination may improve following adaptation. In this work, I construct a
model of the TC, FS, and RS cells comprising a single barrel system-the model
incorporates realistic synaptic connectivity and dynamics and simulates both
angular direction (through the spatial pattern of TC activation) and velocity
(through synchrony of the TC population spikes) of a deflection of the primary
whisker, and I use the model to examine direction and velocity selectivity of
barrel RS cells before and after adaptation. I find that velocity and direction
selectivity of individual RS cells (measured over multiple trials) sharpens
following adaptation, but stimulus discrimination using a simple linear
classifier by the RS population response during a single trial (a more
biologically meaningful measure than single cell discrimination over multiple
trials) exhibits strikingly different behavior-velocity discrimination is similar
both before and after adaptation, while direction classification improves
substantially following adaptation. This is the first model, to my knowledge,
that simulates both whisker deflection velocity and angular direction and
examines the ability of the RS population response to pinpoint both stimulus
features within the context of adaptation.
PMID- 29946251
TI - A Technical Note on the PainChekTM System: A Web Portal and Mobile Medical Device
for Assessing Pain in People With Dementia.
AB - Background: Pain in dementia is predominant particularly in the advanced stages
or in those who are unable to verbalize. Uncontrolled pain alters the course of
behaviors in patients with dementia making them perturbed, unsettled, and
devitalized. Current measures of assessing pain in this population group are
inadequate and underutilized in clinical practice because they lack systematic
evaluation and innovative design. Objective: To describe a novel method and
system of pain assessment using a combination of technologies: automated facial
recognition and analysis (AFRA), smart computing, affective computing, and cloud
computing (Internet of Things) for people with advanced dementia. Methods and
Results: Cognification and affective computing were used to conceptualize the
system. A computerized clinical system was developed to address the challenging
problem of identifying pain in non-verbal patients with dementia. The system is
composed of a smart device enabled app (App) linked to a web admin portal (WAP).
The App "PainChekTM" uses AFRA to identify facial action units indicative of pain
presence, and user-fed clinical information to calculate a pain intensity score.
The App has various functionalities including: pain assessment, pain monitoring,
patient profiling, and data synchronization (into the WAP). The WAP serves as a
database that collects the data obtained through the App in the clinical setting.
These technologies can assist in addressing the various characteristics of pain
(e.g., subjectivity, multidimensionality, and dynamicity). With over 750 paired
assessments conducted, the App has been validated in two clinical studies (n =
74, age: 60-98 y), which showed sound psychometric properties: excellent
concurrent validity (r = 0.882-0.911), interrater reliability (Kw = 0.74-0.86),
internal consistency (alpha = 0.925-0.950), and excellent test-retest reliability
(ICC = 0.904), while it possesses good predictive validity and discriminant
validity. Clinimetric data revealed high accuracy (95.0%), sensitivity (96.1%),
and specificity (91.4%) as well as excellent clinical utility (0.95).
Conclusions: PainChekTM is a comprehensive and evidence-based pain management
system. This novel approach has the potential to transform pain assessment in
people who are unable to verbalize because it can be used by clinicians and
carers in everyday clinical practice.
PMID- 29946252
TI - Sex Differences in Healthspan Predict Lifespan in the 3xTg-AD Mouse Model of
Alzheimer's Disease.
AB - Mouse models of Alzheimer's disease (AD) exhibit marked differences in life
expectancy depending on their genotype and sex. The assessment of frailty could
provide a measure of healthspan to facilitate comparisons between different AD
models. We used a validated mouse frailty index (FI) assessment tool to explore
genotype and sex differences in lifespan and healthspan of 3xTg-AD mice and their
B6129F2 wild-type (WT) controls. This tool is based on an approach commonly used
in people and quantifies frailty by counting the accumulation of age-related
health deficits. The number of deficits in an individual divided by the total
number measured yields an FI score theoretically between 0 and 1, with higher
scores denoting more frailty. Male 3xTg-AD mice aged 300-600 days had higher FI
scores (Mean FI = 0.21 +/- 0.03) than either male WT (Mean FI = 0.15 +/- 0.01) or
female 3xTg-AD mice (Mean FI = 0.10 +/- 0.01), and the elevated frailty scores
were accompanied by parallel increases in mortality. Frailty increased
exponentially with age, and higher rates of deficit accumulation elevated
mortality risk in all groups of mice. When mice were stratified by FI score,
frailty predicted mortality, at least in females. Therefore, the mouse clinical
FI provides a valuable tool for evaluating healthspan in mouse models of AD with
different lifespans.
PMID- 29946253
TI - Multi-Drug Resistant Coliform: Water Sanitary Standards and Health Hazards.
AB - Water constitutes and sustains life; however, its pollution afflicts its
necessity, further worsening its scarcity. Coliform is one of the largest groups
of bacteria evident in fecally polluted water, a major public health concern.
Coliform thrive as commensals in the gut of warm-blooded animals, and are
indefinitely passed through their feces into the environment. They are also
called as model organisms as their presence is indicative of the prevalence of
other potential pathogens, thus coliform are and unanimously employed as adept
indicators of fecal pollution. As only a limited accessible source of fresh water
is available on the planet, its contamination severely affects its usability.
Coliform densities vary geographically and seasonally which leads to the lack of
universally uniform regulatory guidelines regarding water potability often leads
to ineffective detection of these model organisms and the misinterpretation of
water quality status. Remedial measures such as disinfection, reducing the
nutrient concentration or re-population doesn't hold context in huge lotic
ecosystems such as freshwater rivers. There is also an escalating concern
regarding the prevalence of multi-drug resistance in coliforms which renders
antibiotic therapy incompetent. Antimicrobials are increasingly used in
household, clinical, veterinary, animal husbandry and agricultural settings. Sub
optimal concentrations of these antimicrobials are unintentionally but regularly
dispensed into the environment through seepages, sewages or runoffs from clinical
or agricultural settings substantially adding to the ever-increasing pool of
antibiotic resistance genes. When present below their minimum inhibitory
concentration (MIC), these antimicrobials trigger the transfer of antibiotic
resistant genes that the coliform readily assimilate and further propagate to
pathogens, the severity of which is evidenced by the high Multiple Antibiotic
Resistance (MAR) index shown by the bacterial isolates procured from the
environmental. This review attempts to assiduously anthologize the use of
coliforms as water quality standards, their existent methods of detection and the
issue of arising multi-drug resistance in them.
PMID- 29946254
TI - Prevalence Estimates for Pharmacological Neuroenhancement in Austrian University
Students: Its Relation to Health-Related Risk Attitude and the Framing Effect of
Caffeine Tablets.
AB - Background: Pharmacological neuroenhancement (PN) is defined as the use of
illicit or prescription drugs by healthy individuals for cognitive-enhancing
purposes. The present study aimed (i) to investigate whether including caffeine
tablets in the definition of PN within a questionnaire increases the PN
prevalence estimate (framing effect), (ii) to investigate whether the health
related risk attitude is increased in students who use PN. Materials and methods:
Two versions of a paper-and-pencil questionnaire (first version included caffeine
tablets in the definition of PN, the second excluded caffeine tablets) were
distributed among university students at the University of Graz, Austria. The
unrelated question model (UQM) was used to estimate the 12-month PN prevalence
and the German version of the 30-item Domain-Specific Risk-Taking (DOSPERT) scale
to assess the health-related risk attitude. Moreover, large-sample z-tests (alpha
= 0.05) were performed for comparing the PN prevalence estimates of two groups.
Results: Two thousand four hundred and eighty-nine questionnaires were
distributed and 2,284 (91.8%) questionnaires were included in analysis. The
overall PN prevalence estimate for all students was 11.9%. One-tailed large
sample z-tests revealed that the PN estimate for students with higher health
related risk attitude was significantly higher compared to students with lower
health-related risk attitude (15.6 vs. 8.5%; z = 2.65, p = 0.004). Furthermore,
when caffeine tablets were included into the example of PN, the prevalence
estimate of PN was significantly higher compared to the version without caffeine
tablets (14.9 vs. 9.0%; z = 2.20, p = 0.014). Discussion: This study revealed
that the PN prevalence estimate increases when caffeine tablets are included in
the definition of PN. Therefore, future studies investigating the prevalence of,
and predictors for, PN should be performed and interpreted with respect to
potential framing effects. This study further revealed that the PN prevalence
estimate is increased in students with a higher health-related risk attitude
compared to students with a lower one. Therefore, future education and prevention
programs addressing PN in the collective of students should not only inform about
potential side effects of its use but also address the limited effects on
cognition and potential alternatives of PN.
PMID- 29946255
TI - Net Clinical Benefit of Non-vitamin K Antagonist Oral Anticoagulants for Venous
Thromboembolism Prophylaxis in Patients With Cancer: A Systematic Review and
Trade-Off Analysis From 9 Randomized Controlled Trials.
AB - Venous thromboembolism (VTE) is highly prevalent in patients with cancer. Non
vitamin K antagonist oral anticoagulants (NOACs), directly targeting the
enzymatic activity of thrombin or factor Xa, have been shown to be as effective
as and safer than traditional anticoagulation for VTE prophylaxis in no-cancer
patients. However, related studies that focused on the anticoagulation in cancer
patients are lacked, and almost no net clinical benefit (NCB) analyses that
quantified both VTE events and bleeding events have been addressed in this
fragile population. Therefore, we aim to investigate this issue using a
systematic review and NCB analysis. A comprehensive search of Medline, Embase,
and Cochrane Library were performed for randomized controlled trials (RCTs) that
reported the VTE events and major bleeding of NOACs and traditional
anticoagulants in patients with or without cancer. Odds ratios (ORs) and 95%
confidence intervals (CIs) of VTE and bleeding events were calculated using a
random-effects model. The primacy outcome of narrow NCB was calculated by pooling
ORs of VTE and major bleeding, with a weighting of 1.0. Similarly, the broad NCB
was calculated by pooling ORs of VTE and clinically relevant bleeding.
Heterogeneity was assessed through I2 test and Q statistic, and subgroup analyses
were performed on the basis of different patients (VTE patients or acutely ill
patients), comparators (vitamin-K antagonists or low-molecular-weight heparin),
and follow-up duration (<=6 months or >6 months). Overall, 9 RCTs including
41,454 patients were enrolled, of which 2,902 (7%) were cancer patients, and
38,552 (93%) were no-cancer patients; 20,712 (50%) were administrated with NOACs
and 20,742 (50%) were administrated with traditional anticoagulants. The use of
NOACs had a superior NCB than traditional anticoagulation in both cancer patients
(OR: 0.68, 95%CI: 0.50-0.85 for narrow NCB; OR: 0.76, 95%CI: 0.61-0.91 for broad
NCB) and no-cancer patients (OR: 0.75, 95%CI: 0.54-0.96 for narrow NCB; OR: 0.85,
95%CI: 0.67-1.04 for broad NCB), with the estimates mainly from VTE patients
receiving long-term warfarin treatment. In conclusion, NOACs may represent a
better NCB property compared to traditional anticoagulants in cancer patients who
need long-term anticoagulation treatment.
PMID- 29946256
TI - Human Albumin Fragments Nanoparticles as PTX Carrier for Improved Anti-cancer
Efficacy.
AB - For enhanced anti-cancer performance, human serum albumin fragments (HSAFs)
nanoparticles (NPs) were developed as paclitaxel (PTX) carrier in this paper.
Human albumins were broken into fragments via degradation and crosslinked by
genipin to form HSAF NPs for better biocompatibility, improved PTX drug loading
and sustained drug release. Compared with crosslinked human serum albumin NPs,
the HSAF-NPs showed relative smaller particle size, higher drug loading, and
improved sustained release. Cellular and animal results both indicated that the
PTX encapsulated HSAF-NPs have shown good anti-cancer performance. And the
anticancer results confirmed that NPs with fast cellular internalization showed
better tumor inhibition. These findings will not only provide a safe and robust
drug delivery NP platform for cancer therapy, but also offer fundamental
information for the optimal design of albumin based NPs.
PMID- 29946257
TI - Impairing of Serotonin Synthesis by P-Chlorphenylanine Prevents the Forgetting of
Contextual Memory After Reminder and the Protein Synthesis Inhibition.
AB - HIGHLIGHTS The injection of p-chlorophenylalanine, specific blocker of 5-HT
synthesis 3 days before reminder with anisomycin administration prevented
forgetting. It is known that the reminder cause reactivation of the long-term
memory and it leads to reconsolidation of memory. We showed earlier that the
disruption of the reconsolidation of contextual memory in terrestrial snail was
caused by anisomycin, the inhibitor of protein syntheses (Gainutdinova et al.,
2005; Balaban et al., 2014). In this paper we investigated the possible changes
of the memory reconsolidation under the conditions of serotonin deficit, caused
by administration of p-chlorophenylalanine, the inhibitor of tryptophan
hydroxylase synthesis (intermediate stage of the synthesis of serotonin). It was
shown that the forgetting process for contextual memory after reminder and
inhibition of protein synthesis did not occur if the serotonin transmission in
nervous system was impaired. This effect was significantly different from the
direct action of anisomycin, which blocked the reconsolidation of contextual
memory. We concluded that the serotonin system was included to the process of
memory reconsolidation.
PMID- 29946258
TI - Pillars and Pitfalls of the New Pharmacovigilance Legislation: Consequences for
the Identification of Adverse Drug Reactions Deriving From Abuse, Misuse,
Overdose, Occupational Exposure, and Medication Errors.
AB - Rationale: The aim of this study is to investigate if following the
implementation of the Regulation EU/1235/2010 and the Directive 2010/84/EU there
was an increase of individual case safety reports (ICSRs) deriving from a
medication error, abuse, misuse, overdose, or occupational exposure. Other
objectives are the identification of drugs mostly involved in such cases, to
establish if the codification of aforementioned conditions is performed correctly
and, whenever codification errors exist, to identify predictors of codification
errors. Finally, we estimated the magnitude of these errors on signal detection
activities. Methods: ICSRs sent through Campania Region (Italy) spontaneous
reporting system from July 2nd 2012 to December 31th 2017 were used as data
source. A multivariable logistic regression model was used to identify predictors
of codification errors. Four measures of disproportionality were used to
investigate the magnitude of codification errors on a known safety signal or
rather the association between benzodiazepines derivatives and abuse. Results: In
all, 358 (1.4%) out of 25610 ICSRs reported "non-normal use" of drugs, mainly as
cases of abuse. Drugs mostly involved in abuse were "Benzodiazepines derivatives"
(171/358; 47.8%). For medication errors instead, "Other antiseptics and
disinfectants" (9/358; 2.5%). At the first quality control, 125 (34.9%) out of
358 ICSRs did not have a codification of "non-normal use" or codifications were
performed wrongly. Codification errors included misclassification of abuse as
overdose (10/125; 8.0%) and misclassification of medication error as overdose
(7/125; 5.6%) or abuse (7/125; 5.6%). Compared to pharmaceutical companies,
patients/citizens (as reporters) had a 24.88 higher odd (Reporting Odds Ratio
24.88, 95%CI 1.82-449.95; p-value: 0.02) of performing un-classification or
misclassification of aforementioned codifications. Codification errors were
associated with the underestimation of measure of disproportionality' estimates
in the identification of the safety signal "Benzodiazepine derivatives /abuse".
Conclusion: In conclusion, this study found that in Campania Region (southern
Italy) there was an exponential increase of ICSR reporting "non-normal use,"
mainly as cases of abuse, with an improvable proportion of cases
misclassified/unclassified. Moreover, this study found that ICSRs sent by
patients/citizens were associated with an increased odd of un-classification or
misclassification that had a relevant impact on signal detection activities.
PMID- 29946259
TI - Effect of Polyphenols From Campomanesia adamantium on Platelet Aggregation and
Inhibition of Cyclooxygenases: Molecular Docking and in Vitro Analysis.
AB - Campomanesia adamantium is a medicinal plant of the Brazilian Cerrado. Different
parts of its fruits are used in popular medicine to treat gastrointestinal
disorders, rheumatism, urinary tract infections and inflammations. Despite its
widespread use by the local population, the mechanisms involving platelet
aggregation and the inhibition of cyclooxygenase by C. adamantium are unknown.
This study evaluated the chemical composition, antioxidant activities and
potential benefits of the C. adamantium peel extract (CAPE) and its components in
the platelet aggregation induced by arachidonic acid in platelet-rich plasma.
Aspects of the pharmacological mechanism were investigated as follows: platelet
viability, calcium mobilization, levels of the cyclic nucleotides cAMP and cGMP,
thromboxane B2 levels, and the inhibitory effects on COX-1 and COX-2 were studied
in vitro and using molecular docking in the catalytic domain of these proteins.
The major CAPE constituents standing out from the chemical analysis are the
flavonoids, namely those of the flavones and chalcones class. The results showed
that CAPE, quercetin and myricetin significantly decreased arachidonic acid
induced platelet aggregation; the assays showed that CAPE and quercetin decreased
the mobilization of calcium and thromboxane B2 levels in platelets and increased
cAMP and cGMP levels. Moreover, CAPE inhibited the activity of COX-1 and COX-2,
highlighting that quercetin could potentially prevent the access of arachidonic
acid more to the catalytic site of COX-1 than COX-2. These results highlight
CAPE's potential as a promising therapeutic candidate for the prevention and
treatment of diseases associated with platelet aggregation.
PMID- 29946260
TI - Hepatoprotective Effect of San-Cao Granule on Con A-Induced Liver Injury in Mice
and Mechanisms of Action Exploration.
AB - Objective: San-Cao granule (SCG), a traditional Chinese herb formula, has been
used for treating autoimmune hepatitis (AIH) in our clinics for a long time.
However, its active ingredients and mechanisms of action were still unknown due
to its complicated chemical compositions. In the present study, the
pharmacological study of SCG on acute liver injury induced by Concanavalin A (Con
A) was performed to provide a scientific evidence for SCG against liver injury.
Methods: In order to screen active components and predicate mechanisms of action,
an "ingredients-target-disease" interaction network was constructed by network
pharmacology. Then, the pharmacological study was performed to evaluate the
therapeutic effect and the underlying mechanisms of SCG on Con A-induced liver
injury in mice. Results: This research demonstrated the pharmacological effect of
SCG on Con A-induced liver injury, which was through improving the liver
function, relieving the pathological changes of liver tissue, decreasing the
level of pro-inflammatory cytokines, and thus balancing the pro- and anti
inflammatory cytokines. And the anti-inflammatory of SCG may advantage over the
ursodeoxycholic acid (UDCA). Network pharmacology analysis revealed that the
pharmacological effect of SCG might be related to its active ingredients of
taraxanthin, dihydrotanshinone I, isotanshinone I, gamma-sitosterol, 3beta-acetyl
20,25-epoxydammarane-24alpha, and delta-7-stigmastenol. The hepatoprotective
effect of SCG was reflected by suppressing Con A-induced apoptosis which was
mediated by TRAIL and FASL. Conclusion: The combination of network pharmacology
and experimental data has revealed the anti-apoptotic effect of SCG against Con A
induced liver injury.
PMID- 29946261
TI - A Chinese Herbal Formula Ameliorates Pulmonary Fibrosis by Inhibiting Oxidative
Stress via Upregulating Nrf2.
AB - This study aimed to explore the protective effects of a Chinese herbal formula,
Jinshui Huanxian formula (JHF), on experimental pulmonary fibrosis and its
underlying mechanisms. After being treated with single dose of bleomycin (5
mg/kg) intratracheally, rats were orally administered with JHF and pirfenidone
from day 1 to 42, then sacrificed at 7, 14, 28, or 42 days post-bleomycin
instillation. JHF ameliorated bleomycin-induced pathological changes, collagen
deposition in the rat lung and recovered pulmonary function at different days
post-bleomycin instillation. In lungs of JHF-treated rats, the levels of total
superoxide dismutase, catalase and glutathione were higher, and myeloperoxidase
and methane dicarboxylic aldehyde were lower than those in vehicle-treated rats,
respectively. Additionally, JHF inhibited the expression of NADPH oxidase 4
(NOX4) and increased the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in
lung tissues. In vitro, JHF and ruscogenin, a compound of Ophiopogonis Radix
contained in JHF, significantly inhibited transforming growth factor beta1 (TGF
beta1)-induced differentiation of fibroblasts. Furthermore, JHF markedly
decreased the level of reactive oxygen species in TGF-beta1-induced fibroblast.
In line with this, upregulation of NAD(P)H: quinone oxidoreductase 1 and heme
oxygenase 1, and downregulation of NOX4 were found in JHF-treated fibroblast
induced by TGF-beta1. While on the other hand, Nrf2 siRNA could suppress the JHF
mediated inhibition effect on alpha-smooth muscle actin (alpha-SMA), and FN1
expression induced by TGF-beta1 in fibroblasts. These results indicated that JHF
performed remarkably therapeutic and long-term effects on pulmonary fibrosis in
rat and suppressed the differentiation of fibroblast into myofibroblast through
reducing the oxidative response by upregulating Nrf2 signaling. It might provide
a new potential natural drug for the treatment of pulmonary fibrosis.
PMID- 29946263
TI - Accurate Estimation of Running Temporal Parameters Using Foot-Worn Inertial
Sensors.
AB - The aim of this study was to assess the performance of different kinematic
features measured by foot-worn inertial sensors for detecting running gait
temporal events (e.g., initial contact, terminal contact) in order to estimate
inner-stride phases duration (e.g., contact time, flight time, swing time, step
time). Forty-one healthy adults ran multiple trials on an instrumented treadmill
while wearing one inertial measurement unit on the dorsum of each foot. Different
algorithms for the detection of initial contact and terminal contact were
proposed, evaluated and compared with a reference-threshold on the vertical
ground reaction force. The minimum of the pitch angular velocity within the first
and second half of a mid-swing to mid-swing cycle were identified as the most
precise features for initial and terminal contact detection with an inter-trial
median +/- IQR precision of 2 +/- 1 ms and 4 +/- 2 ms respectively. Using these
initial and terminal contact features, this study showed that the ground contact
time, flight time, step and swing time can be estimated with an inter-trial
median +/- IQR bias less than 12 +/- 10 ms and the a precision less than 4 +/- 3
ms. Finally, this study showed that the running speed can significantly affect
the biases of the estimations, suggesting that a speed-dependent correction
should be applied to improve the system's accuracy.
PMID- 29946264
TI - A Highly Automated Computational Method for Modeling of Intracranial Aneurysm
Hemodynamics.
AB - Intracranial aneurysms manifest in a vast variety of morphologies and their
growth and rupture risk are subject to patient-specific conditions that are
coupled with complex, non-linear effects of hemodynamics. Thus, studies that
attempt to understand and correlate rupture risk to aneurysm morphology have to
incorporate hemodynamics, and at the same time, address a large enough sample
size so as to produce reliable statistical correlations. In order to perform
accurate hemodynamic simulations for a large number of aneurysm cases, automated
methods to convert medical imaging data to simulation-ready configuration with
minimal (or no) human intervention are required. In the present study, we develop
a highly-automated method based on the immersed boundary method framework to
construct computational models from medical imaging data which is the key idea is
the direct use of voxelized contrast information from the 3D angiograms to
construct a level-set based computational "mask" for the hemodynamic simulation.
Appropriate boundary conditions are provided to the mask and the dynamics of
blood flow inside the vessels and aneurysm is simulated by solving the Navier
Stokes equations on the Cartesian grid using the sharp-interface immersed
boundary method. The present method does not require body conformal
surface/volume mesh generation or other intervention for model clean-up. The
viability of the proposed method is demonstrated for a number of distinct
aneurysms derived from actual, patient-specific data.
PMID- 29946262
TI - Cell Line Techniques and Gene Editing Tools for Antibody Production: A Review.
AB - The present day modern formulation practices for drugs are based on newer tools
and techniques toward effective utilization. The methods of antibody formulations
are to be revolutionized based on techniques of cell engineering and gene
editing. In the present review, we have discussed innovations in cell engineering
toward production of novel antibodies for therapeutic applications. Moreover,
this review deciphers the use of RNAi, ribozyme engineering, CRISPR-Cas-based
techniques for better strategies for antibody production. Overall, this review
describes the multidisciplinary aspects of the production of therapeutic proteins
that has gained more attention due to its increasing demand.
PMID- 29946265
TI - Assessment of the Health Status of Mussels Mytilus galloprovincialis Along the
Campania Coastal Areas: A Multidisciplinary Approach.
AB - The bivalve Mytilus galloprovincialis has a broad geographic distribution,
represent an important species for the ecology of coastal waters, also
constituting a major aquaculture species. In the present work, molecular and
tissue biomarkers were examined in mussel populations (M. galloprovincialis)
located in four different areas of the coastal water of the Campania Region.
During an annual life cycle, we analyzed the expression patterns of several genes
commonly used to estimate cellular stress response and damage, namely p53, p63,
HSP70, MT-10, and MT-20, related tissue lesions (pathogens, inflammations,
digestive tubules damage), oxidative stress indicators (H2O2, SOD specific
activity) and associated environmental data. The computed Principal Component
Analysis showed that the areas were discernible based on the environmental data
and biomarker results. About animal health status, mussels from Gulf of Pozzuoli
and Naples's harbor did show a thinnest epithelial cell of digestive tubules
compared to mussels sampled from other sampling sites; moreover, high prevalence
of cases of intersex in three of the examinated areas were observed. The presence
of a potential zoonotic pathogen (Nocardia crassostreae) was identified,
appearing as an important possible emerging disease. We also reported the OIE
notifiable protozoa Marteilia refringens in three areas out of four. The likely
impact of both observed pathogens on the mussel health and shellfish aquaculture
needs to be urgently addressed. Results are discussed considering animal
histopathological health parameters and biological effects.
PMID- 29946267
TI - Cellular Mechanisms of Myocardial Depression in Porcine Septic Shock.
AB - The complex pathogenesis of sepsis and septic shock involves myocardial
depression, the pathophysiology of which, however, remains unclear. In this
study, cellular mechanisms of myocardial depression were addressed in a
clinically relevant, large animal (porcine) model of sepsis and septic shock.
Sepsis was induced by fecal peritonitis in eight anesthetized, mechanically
ventilated, and instrumented pigs of both sexes and continued for 24 h. In eight
control pigs, an identical experiment but without sepsis induction was performed.
In vitro analysis of cardiac function included measurements of action potentials
and contractions in the right ventricle trabeculae, measurements of sarcomeric
contractions, calcium transients and calcium current in isolated cardiac
myocytes, and analysis of mitochondrial respiration by ultrasensitive oxygraphy.
Increased values of modified sequential organ failure assessment score and serum
lactate levels documented the development of sepsis/septic shock, accompanied by
hyperdynamic circulation with high heart rate, increased cardiac output,
peripheral vasodilation, and decreased stroke volume. In septic trabeculae,
action potential duration was shortened and contraction force reduced. In septic
cardiac myocytes, sarcomeric contractions, calcium transients, and L-type calcium
current were all suppressed. Similar relaxation trajectory of the intracellular
calcium-cell length phase-plane diagram indicated unchanged calcium
responsiveness of myofilaments. Mitochondrial respiration was diminished through
inhibition of Complex II and Complex IV. Defective calcium handling with reduced
calcium current and transients, together with inhibition of mitochondrial
respiration, appears to represent the dominant cellular mechanisms of myocardial
depression in porcine septic shock.
PMID- 29946266
TI - Are Polyunsaturated Fatty Acids Implicated in Histaminergic Dysregulation in
Bipolar Disorder?: AN HYPOTHESIS.
AB - Bipolar disorder (BD) is an extremely disabling psychiatric disease,
characterized by alternate states of mania (or hypomania) and depression with
euthymic states in between. Currently, patients receive pharmacological treatment
with mood stabilizers, antipsychotics, and antidepressants. Unfortunately, not
all patients respond well to this type of treatment. Bipolar patients are also
more prone to heart and metabolic diseases as well as a higher risk of suicide
compared to the healthy population. For a correct brain function is indispensable
a right protein and lipids (e.g., fatty acids) balance. In particular, the amount
of fatty acids in the brain corresponds to a 50-70% of the dry weight. It has
been reported that in specific brain regions of BD patients there is a reduction
in the content of unsaturated n-3 fatty acids. Accordingly, a diet rich in n-3
fatty acids has beneficial effects in BD patients, while their absence or high
levels of saturated fatty acids in the diet are correlated to the risk of
developing the disease. On the other hand, the histamine system is likely to be
involved in the pathophysiology of several psychiatric diseases such as BD.
Histamine is a neuromodulator involved in arousal, motivation, and energy
balance; drugs acting on the histamine receptor H3 have shown potential as
antidepressants and antipsychotics. The histaminergic system as other
neurotransmission systems can be altered by fatty acid membrane composition. The
purpose of this review is to explore how polyunsaturated fatty acids content
alterations are related to the histaminergic system modulation and their impact
in BD pathophysiology.
PMID- 29946268
TI - A Meta-Analysis of miR-499 rs3746444 Polymorphism for Cancer Risk of Different
Systems: Evidence From 65 Case-Control Studies.
AB - MicroRNAs (miRNAs) are a class of endogenous, short and non-coding RNAs that may
play important roles in the pathogenesis of tumor. The associations between
microRNA-499 rs3746444 polymorphism and cancer risk in different systems remain
inconclusive. This article is aimed to obtain more exact estimation of these
relationships through a meta-analysis based on 52,456 individuals. We retrieved
relevant and eligible studies from Pubmed and Embase database up to January 10,
2018. ORs and 95% CIs were used to estimate the associations between miR-499
polymorphism and cancer susceptibility in different systems. All analyses were
performed using the Stata 11.0 software. A total of 65 case-control studies were
retrieved using explicit inclusion and exclusion criteria. The study included
23,762 cases and 28,694 controls. Overall cancer analysis showed the association
between miR-499 polymorphism and susceptibility to cancer was significant.
MicroRNA-499 rs3746444 was found to be significantly associated with increased
risk of cancer of the respiratory system (CC vs. TT: OR = 1.575, 95% CI = 1.268
1.955, CC vs. TC+TT: OR = 1.527, 95% CI = 1.232-1.892), digestive system (CC vs.
TT: OR = 1.153, 95% CI = 1.027-1.295; TC vs. TT: OR = 1.109, 95% CI = 1.046
1.176; CC+TC vs. TT: OR = 1.112, 95% CI = 1.018-1.216; CC vs. TC+TT: OR = 1.137,
95% CI = 1.016-1.272; C vs. T: OR = 1.112, 95% CI = 1.025-1.206), urinary system
(TC vs. TT: OR = 1.307, 95% CI = 1.130-1.512; CC+TC vs. TT: OR = 1.259, 95% CI =
1.097-1.446; C vs. T: OR = 1.132, 95% CI = 1.014-1.264), and gynecological system
(C vs. T: OR = 1.169, 95% CI = 1.002-1.364). In the subgroup analysis by
ethnicity, the result showed that significant association with an increased
cancer risk was found in Asian. Subgroup analysis based on type of tumor was also
performed, miR-499 rs3746444 is associated with susceptibility of cervical
squamous cell carcinoma, lung cancer, prostate cancer, and hepatocellular
carcinoma.
PMID- 29946269
TI - Do Parent Mental Illness and Family Living Arrangement Moderate the Effects of
the Aussie Optimism Program on Depression and Anxiety in Children?
AB - Parent mental illness and family living arrangement are associated with
depression and anxiety in children, and may influence the effects of programs
that aim to prevent these disorders. This study investigated whether these family
context factors moderated the intervention effects of the enhanced Aussie
Optimism Positive Thinking Skills program on depression and anxiety in primary
school children. The intervention was a universal, cognitive-behavioral program,
with a one hour session each week for 10 weeks, delivered by trained teachers.
The participants were 502 children from 13 private schools, aged 9-11, with 347
in the intervention group and 155 in the control group. There were 267 females
and 235 males. Data from 502 parents was also included. A cluster randomized
controlled trial design was used, including eight intervention schools and five
control schools. Depression and anxiety were assessed at pre-test, post-test, and
6-months follow-up. Information on parent mental illness and family living
arrangement was collected through a parent questionnaire. The data was analyzed
using covariance analysis with Generalized Linear Mixed Methods. At baseline,
depressive and anxiety symptoms did not differ significantly based on parent
mental illness. Symptoms of depression at baseline were significantly higher for
children from a higher-risk family living arrangement, but anxiety symptoms were
not. Parent mental illness and family living arrangement did not moderate the
effects of the program on depression and anxiety at post-test or 6-months follow
up. Parent mental illness moderated the intervention effects on negative self
esteem, an aspect of depression, at post-test, with improvements seen only for
children who did not have a parent with a mental illness. The findings indicate
an association between family living arrangement and depressive symptoms in
children. The findings suggest that the program is effective for children
regardless of parent mental illness or family living arrangement, although parent
mental illness has the capacity to influence the program's outcomes.
PMID- 29946270
TI - Efficacy and Acceptability of Interventions for Attenuated Positive Psychotic
Symptoms in Individuals at Clinical High Risk of Psychosis: A Network Meta
Analysis.
AB - Background: Attenuated positive psychotic symptoms represent the defining
features of the clinical high-risk for psychosis (CHR-P) criteria. The
effectiveness of each available treatment for reducing attenuated positive
psychotic symptoms remains undetermined. This network meta-analysis (NMA)
investigates the consistency and magnitude of the effects of treatments on
attenuated positive psychotic symptoms in CHR-P individuals, weighting the
findings for acceptability. Methods: Web of Science (MEDLINE), PsycInfo, CENTRAL
and unpublished/gray literature were searched up to July 18, 2017. Randomized
controlled trials in CHR-P individuals, comparing at least two interventions and
reporting on attenuated positive psychotic symptoms at follow-up were included,
following PRISMA guidelines. The primary outcome (efficacy) was level of
attenuated positive psychotic symptoms at 6 and 12 months; effect sizes reported
as standardized mean difference (SMD) and 95% CIs in mean follow-up scores
between two compared interventions. The secondary outcome was treatment
acceptability [reported as odds ratio (OR)]. NMAs were conducted for both primary
and secondary outcomes. Treatments were cluster-ranked by surface under the
cumulative ranking curve values for efficacy and acceptability. Assessments of
biases, assumptions, sensitivity analyses and complementary pairwise meta
analyses for the primary outcome were also conducted. Results: Overall, 1,707
patients from 14 studies (57% male, mean age = 20) were included, representing
the largest evidence synthesis of the effect of preventive treatments on
attenuated positive psychotic symptoms to date. In the NMA for efficacy,
ziprasidone + Needs-Based Intervention (NBI) was found to be superior to NBI (SMD
= -1.10, 95% CI -2.04 to -0.15), Cognitive Behavioral Therapy-French and Morrison
protocol (CBT-F) + NBI (SMD = -1.03, 95% CI -2.05 to -0.01), and risperidone +
CBT-F + NBI (SMD = -1.18, 95% CI -2.29 to -0.07) at 6 months. However, these
findings did not survive sensitivity analyses. For acceptability, aripiprazole +
NBI was significantly more acceptable than olanzapine + NBI (OR = 3.73; 95% CI
1.01 to 13.81) at 12 months only. No further significant NMA effects were
observed at 6 or 12 months. The results were not affected by inconsistency or
evident small-study effects, but only two studies had an overall low risk of
bias. Conclusion: On the basis of the current literature, there is no robust
evidence to favor any specific intervention for improving attenuated positive
psychotic symptoms in CHR-P individuals.
PMID- 29946271
TI - Patterns of Substance Abuse in Offenders With Schizophrenia- Illness-Related or
Criminal Life-Style?
AB - Objective: The impact of substance abuse on violent behavior in patients
suffering from schizophrenia is well-known. However, the association between the
pattern of substance abuse and certain aspects of criminal behavior like the
severity of offense, the previous history of violence and the age at onset of the
criminal career is still unclear. Method: To assess the relationship between
substance abuse, schizophrenia and violent behavior we examined healthy non
offenders; healthy offenders; non-offenders suffering from schizophrenia; and
offenders suffering from schizophrenia, with respect to different patterns of
substance abuse (none, alcohol only, illicit drugs only, and multiple
substances). Results: Healthy offenders as well as offenders and non-offenders
suffering from schizophrenia are characterized by increased rates of alcohol and
illicit drug abuse. Especially multiple substance abuse appears to lower the
threshold of aggression and illegal behavior. This effect is more pronounced in
subjects suffering from schizophrenia. In both offender groups the abuse of
psychoactive substances is associated with an earlier onset of the criminal
career, but has no impact on the severity of the offenses. Conclusion: Our
results point to the need for a differentiated view on the contribution of
substance abuse to the criminality of subjects suffering from schizophrenia.
PMID- 29946272
TI - Oxycodone Self-Administration Induces Alterations in Expression of Integrin,
Semaphorin and Ephrin Genes in the Mouse Striatum.
AB - Oxycodone is one a commonly used medication for pain, and is also a widely abused
prescription opioid, like other short-acting MOPr agonists. Neurochemical and
structural adaptations in brain following chronic MOPr-agonist administration are
thought to underlie pathogenesis and persistence of opiate addiction. Many axon
guidance molecules, such as integrins, semaphorins, and ephrins may contribute to
oxycodone-induced neuroadaptations through alterations in axon-target connections
and synaptogenesis, that may be implicated in the behaviors associated with
opiate addiction. However, little is known about this important area. The aim of
this study is to investigate alterations in expression of selected integrin,
semaphorin, ephrins, netrin, and slit genes in the nucleus accumbens (NAc) and
caudate putamen (CPu) of mice following extended 14-day oxycodone self
administration (SA), using RNAseq. Methods: Total RNA from the NAc and CPu were
isolated from adult male C57BL/6J mice within 1 h after the last session of
oxycodone in a 14-day self-administration paradigm (4h/day, 0.25 mg/kg/infusion,
FR1) or from yoked saline controls. Gene expressions were examined using RNA
sequencing (RNA-Seq) technology. RNA-Seq libraries were prepared using Illumina's
TruSeq(r) Stranded Total RNA LT kit. The reads were aligned to the mouse
reference genome (version mm10) using STAR. DESeq2 was applied to the counts of
protein coding genes to estimate the fold change between the treatment groups.
False Discovery Rate (FDR) q < 0.1 were used to select genes that have a
significant expression change. For selection of a subset of genes related to axon
guidance pathway, REACTOME was used. Results: Among 38 known genes of the
integrin, semaphorin, and ephrin gene families, RNA-seq data revealed up
regulation of six genes in the NAc: heterodimer receptor, integrins Itgal, Itgb2,
and Itgam, and its ligand semaphorin Sema7a, two semaphorin receptors, plexins
Plxnd1 and Plxdc1. There was down-regulation of eight genes in this region: two
integrin genes Itga3 and Itgb8, semaphorins Sema3c, Sema4g, Sema6a, Sema6d,
semaphorin receptor neuropilin Nrp2, and ephrin receptor Epha3. In the CPu, there
were five differentially expressed axon guidance genes: up-regulation of three
integrin genes, Itgal, Itgb2, Itga1, and down-regulation of Itga9 and ephrin
Efna3 were thus observed. No significant alterations in expression of Netrin-1 or
Slit were observed. Conclusion: We provide evidence for alterations in the
expression of selective axon guidance genes in adult mouse brain following
chronic self-administration of oxycodone. Further examination of oxycodone
induced changes in the expression of these specific axon guidance molecules and
integrin genes in relation to behavior may provide new insights into development
of addiction to oxycodone.
PMID- 29946273
TI - Machine Learning: An Approach in Identifying Risk Factors for Coercion Compared
to Binary Logistic Regression.
AB - Introduction: Although knowledge about negative effects of coercive measures in
psychiatry exists, its prevalence is still high in clinical routine. This study
aimed at define risk factors and test machine learning algorithms for their
accuracy in the prediction of the risk to being subjected to coercive measures.
Methods: In a sample of involuntarily hospitalized patients (n = 393) at the
University Hospital of Psychiatry Zurich, we analyzed risk factors for the
experience of coercion (n = 170 patients) using chi-square tests and Mann Whitney
U tests. We trained machine learning algorithms [logistic regression, Supported
Vector Machine (SVM), and decision trees] with these risk factors and tested
obtained models for their accuracy via five-fold cross validation. To verify the
results we compared them to binary logistic regression. Results: In a model with
8 risk-factors which were available at admission, the SVM algorithm identified
102 out of 170 patients, which had experienced coercion and 174 out of 223
patients without coercion (69% accuracy with 60% sensitivity and 78% specificity,
AUC 0.74). In a model with 18 risk-factors, available after discharge, the
logistic regression algorithm identified 121 out of 170 with and 176 out of 223
without coercion (75% accuracy, 71% sensitivity, and 79% specificity, AUC 0.82).
Discussion: Incorporating both clinical and demographic variables can help to
estimate the risk of experiencing coercion for psychiatric patients. This study
could show that trained machine learning algorithms are comparable to binary
logistic regression and can reach a good or even excellent area under the curve
(AUC) in the prediction of the outcome coercion/no coercion when cross validation
is used. Due to the better generalizability machine learning is a promising
approach for further studies, especially when more variables are analyzed. More
detailed knowledge about individual risk factors may help to prevent the
occurrence of situations involving coercion.
PMID- 29946274
TI - Cognitive Behavioral Therapy for Insomnia as Adjunctive Therapy to Antipsychotics
in Schizophrenia: A Case Report.
AB - The authors present the case of a 38-year-old man with schizophrenia and with
severe insomnia, who attempted suicide twice during oral drug therapy with
risperidone. The patient slept barely 2 or 3 h per night, and he frequently took
half days off from work due to excessive daytime sleepiness. As a maladaptive
behavior to insomnia, he progressively spent more time lying in bed without
sleeping, and he repeatedly thought about his memories, which were reconstructed
from his hallucinations. His relatives and friends frequently noticed that his
memories were not correct. Consequently, the patient did not trust his memory,
and he began to think that the hallucinations controlled his life. During his
insomniac state, he did not take antipsychotic drugs regularly because of his
irregular meal schedule due to his excessive daytime sleepiness. The authors
started cognitive behavioral therapy for insomnia (CBT-i) with aripiprazole long
acting injection (LAI). CBT-i is needed to be tailored to the patient's specific
problems, as this case showed that the patient maladaptively use chlorpromazine
as a painkiller, and he exercised in the middle of the night because he believed
he can fall asleep soon after the exercise. During his CBT-i course, he learned
how to evaluate and control his sleep. The patient, who originally wanted to be
short sleeper, began to understand that adequate amounts of sleep would
contribute to his quality of life. He finally stopped taking chlorpromazine and
benzodiazepine as sleeping drugs while taking suvorexant 20 mg. Through CBT-i, he
came to understand that poor sleep worsened his hallucinations, and consequently
made his life miserable. He understood that good sleep eased his hallucinations,
ameliorated his daytime sleepiness and improved his concentration during working
hours. Thus, he was able to improve his self-esteem and self-efficacy by
controlling his sleep. In this case report, the authors suggest that CBT-i can be
an effective therapy for schizophrenia patients with insomnia to the same extent
of other psychiatric and non-psychiatric patients.
PMID- 29946275
TI - An Eye Movement Desensitization and Reprocessing (EMDR) Group Intervention for
Syrian Refugees With Post-traumatic Stress Symptoms: Results of a Randomized
Controlled Trial.
AB - The number of refugees has increased significantly over the past few years. PTSD
and depression are among the most common mental health problems among refugees.
Eye Movement Desensitization and Reprocessing (EMDR), an effective treatment for
PTSD, is usually administered individually. The availability of mental health
resources would be greatly enhanced when EMDR can be delivered to groups. The
EMDR G-TEP is a group protocol based on Early EMDR intervention protocols. There
is clinical evidence and one field study published on the effect of EMDR G-TEP
and there is only one RCT published on the treatment of PTSD and depression in a
refugee camp. The aim of our study was to investigate the efficacy of EMDR G-TEP
in treating post-trauma symptoms and depression and preventing the development of
chronic PTSD among refugees living in a refugee camp. 47 adult participants with
PTSD symptoms were randomly allocated to experimental (n = 18) and control (n =
29) groups. We measured Impact of Event Scale (IES-R), Beck Depression Inventory
II (BDI-II) and International Neuropsychiatric Interview (MINI) at pre-, post-
and 4-week follow-up. Analysis of the results showed that the EMDR G-TEP group
had significantly lower PTSD and depression symptoms after intervention. The
percentage of PTSD diagnosis decreased from 100 to 38.9% in the EMDR G-TEP group
and was unchanged in the control group. Following the EMDR G-TEP intervention
61.1% of the experimental group no longer had a PTSD diagnosis; this decrease was
maintained at 4 weeks follow-up. In the control group the percentage of people
who no longer met the diagnostic criteria for PTSD was 10.3% post-test and 6.9%
at 4 weeks follow-up. A significant decrease in depression symptoms from pre-test
levels was found in EMDR group but not in the control group follow up-test. This
study indicated that EMDR G-TEP effectively reduced PTSD symptoms among refugees
living in a camp, after two treatment sessions conducted over a period of 3 days.
Further studies need to be performed using a larger number of participants,
followed for a longer period of time and given more treatment sessions to
strengthen our findings.
PMID- 29946276
TI - The Future Cybersecurity Workforce: Going Beyond Technical Skills for Successful
Cyber Performance.
AB - One of the challenges in writing an article reviewing the current state of cyber
education and workforce development is that there is a paucity of quantitative
assessment regarding the cognitive aptitudes, work roles, or team organization
required by cybersecurity professionals to be successful. In this review, we
argue that the people who operate within the cyber domain need a combination of
technical skills, domain specific knowledge, and social intelligence to be
successful. They, like the networks they operate, must also be reliable,
trustworthy, and resilient. Defining the knowledge, skills, attributes, and other
characteristics is not as simple as defining a group of technical skills that
people can be trained on; the complexity of the cyber domain makes this a unique
challenge. There has been little research devoted to exactly what attributes
individuals in the cyber domain need. What research does exist places an emphasis
on technical and engineering skills while discounting the important social and
organizational influences that dictate success or failure in everyday settings.
This paper reviews the literature on cyber expertise and cyber workforce
development to identify gaps and then argues for the important contribution of
social fit in the highly complex and heterogenous cyber workforce. We then
identify six assumptions for the future of cybersecurity workforce development,
including the requirement for systemic thinkers, team players, a love for
continued learning, strong communication ability, a sense of civic duty, and a
blend of technical and social skill. Finally, we make recommendations for social
and cognitive metrics which may be indicative of future performance in cyber work
roles to provide a roadmap for future scholars.
PMID- 29946277
TI - Cognitive Emotion Regulation Strategies in Anxiety and Depression Understood as
Types of Personality.
AB - The identification of distinctive and overlapping features of anxiety and
depression remains an important scientific problem. Currently, the literature
does not allow to determine stable similarities and differences in the use of
cognitive emotion regulation strategies (CERS) in anxiety and depression,
especially concerning the adaptive strategies. Consequently, the aim of this
study was to identify the overlapping and distinctive patterns of CERS use in the
recently proposed types of anxiety and depression in a general population. In
this dimensional approach, types of anxiety and depression are considered as
personality types and distinguished based on their specific structural
composition and functional role (reactive or regulative) in stimulation
processing. 1,632 participants from a representative sample completed the Anxiety
and Depression Questionnaire (measuring the Arousal and Apprehension Types of
anxiety and the Valence and Anhedonic Types of depression) and the Cognitive
Emotion Regulation Questionnaire. Regression analyses were conducted with the
affective types as predictors. The co-occurrence of the types was accounted for
in order to examine their independent relationships with the CERS. We found that
reactive arousal anxiety was not related to any strategies, while regulative
apprehension anxiety primarily predicted the use of rumination, which is
presumably related to the type's cognitive structural components. The strategy
specific to reactive valence depression was other-blame (as predicted by the high
negative affect in its structure), and the regulative, most structurally complex
anhedonic depression predicted the use of the largest number of strategies,
including the adaptive ones. The relationships between the types of depression
and self-blame and refocus on planning were moderated by sex but the effects were
small. These findings fit into the current trend of exploring the shared and
specific features of anxiety and depression, which might facilitate their
differentiation by identifying CERS that are characteristic for the specific
types. This information can be used for supporting diagnosis and targeting
selected strategies in therapy both in clinical and non-clinical populations.
PMID- 29946278
TI - A Theoretical and Clinical Framework for Parental Burnout: The Balance Between
Risks and Resources (BR2).
AB - Parental burnout is a specific syndrome resulting from enduring exposure to
chronic parenting stress. But why do some parents burn out while others, facing
the same stressors, do not? The main aim of this paper was to propose a theory of
parental burnout capable of predicting who is at risk of burnout, explaining why
a particular parent burned out and why at that specific point in time, and
providing directions for intervention. The secondary goal was to operationalize
this theory in a tool that would be easy to use for both researchers and
clinicians. The results of this two-wave longitudinal study conducted on 923
parents suggest that the Balance between Risks and Resources (BR2) theory
proposed here is a relevant framework to predict and explain parental burnout.
More specifically, the results show that (1) the BR2 instrument reliably measures
parents' balance between risks (parental stress-enhancing factors) and resources
(parental stress-alleviating factors), (2) there is a strong linear relationship
between BR2 score and parental burnout, (3) parental burnout results from a
chronic imbalance of risks over resources, (4) BR2 predicts parental burnout
better than job burnout and (5) among the risk and resource factors measured in
BR2, risks and resources non-specific to parenting (e.g., low stress-management
abilities, perfectionism) equally predict parental and job burnout, while risks
and resources specific to parenting (e.g., childrearing practices, coparenting)
uniquely predict parental burnout.
PMID- 29946279
TI - Moralized Health-Related Persuasion Undermines Social Cohesion.
AB - Integrating theory and research on persuasion, moralization, and intergroup
relations, the present research aims to highlight the far-reaching impact of
health-related persuasion on society. I propose that governments' health-related
persuasion leads to the emergence of new social norms, and in particular moral
norms. Importantly, moral norms provide strong behavioral imperatives and are
seen as binding for group members. This suggests that moralized persuasion has a
strong potential to divide society along the lines of citizens who conform to and
citizens who deviate from health-related moral norms. Thus, departing from the
traditional focus on targets of persuasion, the present research focuses on those
holding a moralized view on health and lifestyle. Key aspects of social cohesion
as defined by the OECD (2011) have been tested across four studies. The main
hypothesis tested is that those conforming to the norm (e.g., non-smokers, normal
weight people, people with healthy lifestyles) will stigmatize those deviating
from the norm (e.g., smokers, overweight people, people with unhealthy
lifestyles). Flowing from stigmatization, less inclusion, lower solidarity with
and greater endorsement of unequal treatment of those deviating from the moral
norm are predicted. Four survey studies (total N = 1568) examining the proposed
associations among non-smokers, normal weight people, and employees with healthy
lifestyles are presented. The studies provide unanimous support for the
hypothesis, with meta-analysis providing further support for the reliability of
the findings. Consistent across studies, social cohesion indicators were
negatively affected by health moralization through stigmatization of those
deviating from health-related moral norms. Findings highlight an under
acknowledged potential of moralized health-related persuasion to divide society,
thereby undermining cohesion and the achievement of important societal goals. In
the discussion, limitations and relevant routes for future research are
highlighted. Recommendations are derived for policy makers, institutions,
employers, and individuals.
PMID- 29946280
TI - Fourth-Party Evaluation of Third-Party Pro-social Help and Punishment: An ERP
Study.
AB - Pro-social behaviors have been adequately studied by neuroscientists. However,
few neural studies have focused on the social evaluation of pro-social behaviors,
and none has compared the neural correlates of different pro-social decision
evaluations. By fourth-party evaluation of third-party punishment/help dictator
game paradigm, we explored the third-party pro-social behaviors and derived
feedback-related negativity (FRN) from the electroencephalogram. Different from
previous event-related potentials (ERP) studies, we simultaneously focused on two
different third-party pro-social behaviors, which were called third-party help
and third-party punishment. For the first time, we compared the different neural
processes of fourth-party evaluation on third-party help and punishment.
Behavioral results showed that fourth-party bystanders appreciated the help
behavior of the third party even more than the punishment behavior. ERP results
revealed that fourth-party bystanders' FRN amplitudes were modulated by the third
party behaviors. Under the assignment condition (70:30) with help/punishment
magnitude 45 and (90:10) with magnitude 80, the third-party help elicited a
larger FRN than third-party punishment; whereas under the condition (90:10) with
help/punishment magnitude 45, the difference between FRN amplitudes disappeared.
These results indicated that fourth-party bystanders ultimately agreed more with
helpful third parties; however, after they witnessed the norm violation, they
expected the third parties to punish the norm violators immediately. This
phenomenon appears only when the third-party actors can achieve justice between
norm violators and victims.
PMID- 29946281
TI - Context Modulates Congruency Effects in Selective Attention to Social Cues.
AB - Head and gaze directions are used during social interactions as essential cues to
infer where someone attends. When head and gaze are oriented toward opposite
directions, we need to extract socially meaningful information despite stimulus
conflict. Recently, a cognitive and neural mechanism for filtering-out
conflicting stimuli has been identified while performing non-social attention
tasks. This mechanism is engaged proactively when conflict is anticipated in a
high proportion of trials and reactively when conflict occurs infrequently. Here,
we investigated whether a similar mechanism is at play for limiting distraction
from conflicting social cues during gaze or head direction discrimination tasks
in contexts with different probabilities of conflict. Results showed that, for
the gaze direction task only (Experiment 1), inverse efficiency (IE) scores for
distractor-absent trials (i.e., faces with averted gaze and centrally oriented
head) were larger (indicating worse performance) when these trials were
intermixed with congruent/incongruent distractor-present trials (i.e., faces with
averted gaze and tilted head in the same/opposite direction) relative to when the
same distractor-absent trials were shown in isolation. Moreover, on distractor
present trials, IE scores for congruent (vs. incongruent) head-gaze pairs in
blocks with rare conflict were larger than in blocks with frequent conflict,
suggesting that adaptation to conflict was more efficient than adaptation to
infrequent events. However, when the task required discrimination of head
orientation while ignoring gaze direction, performance was not impacted by both
block-level and current trial congruency (Experiment 2), unless the cognitive
load of the task was increased by adding a concurrent task (Experiment 3).
Overall, our study demonstrates that during attention to social cues proactive
cognitive control mechanisms are modulated by the expectation of conflicting
stimulus information at both the block- and trial-sequence level, and by the type
of task and cognitive load. This helps to clarify the inherent differences in the
distracting potential of head and gaze cues during speeded social attention
tasks.
PMID- 29946282
TI - New Directions for Preventing Dating Violence in Adolescence: The Study of Gender
Models.
AB - Dating violence is a huge transcultural and alarming phenomenon, directly linked
with endless discrimination against women. The latest research on dating violence
in adolescence shows how dating violence is persistent and common in the
adolescent period as well and pinpoints the origin of gender violence from first
adolescent relationships. This element takes us to considerate how recent gender
violence studies and policies, increased also thanks to international efforts on
this issue, are not bringing expected results, especially among young people.
This mini-review aims to analyze the main characteristics of current gender
studies and policies on dating violence, focusing on percentages with a woman
centered approach, which stresses the consequences of gender violence. Other
gender studies, that consider gender as a relational product, stress the
importance of integrating the analysis of gender models as a key instrument to
understand the main causes of dating violence, providing new elements to develop
effective policies against dating violence. Indeed, gender models of femininity
and masculinity are based on a binary system, which is also a reciprocal
recognition and identity system: gender models define female and male
characteristics, roles, stereotypes, and expectation, being complementary and
foreclosing at the same time. Recent studies on gender relationships, especially
among the youth, allows us to propose a new dialog between dating violence
studies and gender model studies, underling the need of a complete and complex
understanding of gender structure, and of its tensions and contradictions, to put
an end to gender and dating violence, through effective programs.
PMID- 29946284
TI - Behavioral Repertoire Influences the Rate and Nature of Learning in Climbing:
Implications for Individualized Learning Design in Preparation for Extreme Sports
Participation.
AB - Extreme climbing where participants perform while knowing that a simple mistake
could result in death requires a skill set normally acquired in non-extreme
environments. In the ecological dynamics approach to perception and action, skill
acquisition involves a process where the existing repertoire of behavioral
capabilities (or coordination repertoire) of a learner are destabilized and re
organized through practice-this process can expand the individuals affordance
boundaries allowing the individual to explore new environments. Change in
coordination repertoire has been observed in bi-manual coordination and postural
regulation tasks, where individuals begin practice using one mode of coordination
before transitioning to another, more effective, coordination mode during
practice. However, individuals may also improve through practice without
qualitatively reorganizing movement system components-they do not find a new mode
of coordination. To explain these individual differences during learning (i.e.,
whether or not a new action is discovered), a key candidate is the existing
coordination repertoire present prior to practice. In this study, the learning
dynamics of body configuration patterns organized with respect to an indoor
climbing surface were observed and the existing repertoire of coordination
evaluated prior to and after practice. Specifically, performance outcomes and
movement patterns of eight beginners were observed across 42 trials of practice
over a 7-week period. A pre- and post-test scanning procedure was used to
determine existing patterns of movement coordination and the emergence of new
movement patterns after the practice period. Data suggested the presence of
different learning dynamics by examining trial-to-trial performance in terms of
jerk (an indicator of climbing fluency), at the individual level of analysis. The
different learning dynamics (identified qualitatively) included: continuous
improvement, sudden improvement, and no improvement. Individuals showing sudden
improvement appeared to develop a new movement pattern of coordination in terms
of their capability to climb using new body-wall orientations, whereas those
showing continuous improvement did not, they simply improved performance. The
individual who did not improve in terms of jerk, improved in terms of distance
climbed. We discuss implications for determining and predicting how individual
differences can shape learning dynamics and interact with metastable learning
design.
PMID- 29946285
TI - Ecology of Freedom: Competitive Tests of the Role of Pathogens, Climate, and
Natural Disasters in the Development of Socio-Political Freedom.
AB - Many countries around the world embrace freedom and democracy as part of their
political culture. However, culture is at least in part a human response to the
ecological challenges that a society faces; hence, it should not be surprising
that the degree to which societies regulate the level of individual freedom is
related to environmental circumstances. Previous research suggests that levels of
societal freedom across countries are systematically related to three types of
ecological threats: prevalence of pathogens, climate challenges, and natural
disaster threat. Though their incidence overlaps, the literature has not yet
provided a competitive test. Drawing upon the ecocultural framework, we tested
five rival hypotheses, alternately focused on the above ecological factors and
their interactions with economic wealth in explaining country variations in socio
political freedom. Focusing on data from 150 countries, we performed a series of
linear mixed-effects regressions predicting freedom in the domains of politics,
media, and economy. We found that countries with higher pathogen prevalence were
more likely to suppress democracy and media freedom. Economic wealth, however,
moderated the effect of pathogen prevalence on economic freedom, with the main
effect being only found among wealthy countries, but not among poor countries. In
contrast, natural disaster threat predicted political freedom and press freedom
only among poor countries, consistent with the idea that disaster threat
accompanied by poor resources promote socio-political freedom as a means of
increasing collective survival. Throughout our analyses, we found no support for
hypotheses based on climatic challenges. In addition, our multilevel approach
revealed that country scores for socio-political freedom were highly clustered
within world regions, accounting for substantial portions of variance. Overall,
the present research offers a nuanced view of the interplay between ecology and
wealth in the emergence of socio-political freedom. We discuss new directions in
future research considering methodological and theoretical contributions of the
present findings.
PMID- 29946283
TI - Manual Dexterity Is a Strong Predictor of Visuo-Motor Temporal Integration in
Children.
AB - Although visuo-motor temporal integration in children is suggested to be related
to motor control and motor learning, its relevance is still unclear. On the other
hand, visuo-motor temporal integration ability undergoes developmental changes
with age. In the current correlational study, we measured manual dexterity and
visuo-motor temporal integration ability in 132 children with typical development
(age, 4-15 years) and investigated the relationship between the two functions.
The Movement Assessment Battery for Children-2nd edition was used as an indicator
of manual dexterity. The delay detection threshold (DDT) and steepness of the
probability curve for delay detection, which was measured by the delayed visual
feedback detection task for self-generated movement, were used as indices of the
visuo-motor temporal integration ability. The results indicated significant
correlations between manual dexterity/age and DDT/steepness of the probability
curve for delay detection. In addition, hierarchical multiple regression analysis
showed that both manual dexterity and age significantly contributed to visuo
motor temporal integration, indicating a better fit than when only age was
employed as an independent variable. Importantly, there was no interaction effect
between age and manual dexterity. These findings were the first to suggest that
manual dexterity is a significant predictor of visuo-motor temporal integration
ability in children, regardless of age. The present study validated the important
relationship between visuo-motor temporal integration and manual dexterity in
children. Considering the limitations of the current study, including the non
homogeneous sample, further studies are still warranted to validate the results.
PMID- 29946286
TI - Preschoolers' Development of Theory of Mind: The Contribution of Understanding
Psychological Causality in Stories.
AB - This study investigated the relationship between children's abilities to
understand causal sequences and another's false belief. In Experiment 1, we
tested 3-, 4-, 5-, and 6-year-old children (n = 28, 28, 27, and 27, respectively)
using false belief and picture sequencing tasks involving mechanical, behavioral,
and psychological causality. Understanding causal sequences in mechanical,
behavioral, and psychological stories was related to understanding other's false
beliefs. In Experiment 2, children who failed the initial false belief task (n =
50) were reassessed 5 months later. High scorers in the sequencing of the
psychological stories in Experiment 1 were more likely to pass the standard false
belief task than were the low scorers. Conversely, understanding causal sequences
in the mechanical and behavioral stories in Experiment 1 did not predict passing
the false belief task in Experiment 2. Thus, children may understand
psychological causality before they are able to use it to understand false
beliefs.
PMID- 29946287
TI - The Association of Number and Space Under Different Tasks: Insight From a Process
Perspective.
AB - We investigated the Spatial Numerical Association of Response Codes (SNARC)
effect in 240 adults using a parity judgment and a magnitude classification task.
Eight numbers from 1 to 9 except 5 were randomly presented one at a time, half of
the participants were asked to compare these number with the target number 5 in
the magnitude classification task; the other half of the participants were asked
to judge whether these numbers were even or odd. It was called a phase when all
eight numbers were tested; there were in total 16 phases. Detailed analyses of
the changes in response times across the range of numbers and the chronological
trend of the SNARC effect size over 16 phases estimated by a curvilinear
regression model were reported. This phase-to-phase design and analyses provide
an insight into the process of the SNARC effect in different tasks. We found that
the SNARC effect emerged earlier and stayed more stable in magnitude
classification task than in the parity task during the time course. Furthermore,
the size of SNARC effect increased with time in the magnitude classification
task, whereas it fluctuated up and down over time in the parity task. These
findings indicate that the association of the number and space is dynamic and the
process of the SNARC effect varies across tasks.
PMID- 29946289
TI - Psychometric Properties of the 20-Item Toronto Alexithymia Scale in the Chilean
Population.
AB - Alexithymia can be defined as inability to identify and describe emotions in the
self. Has shown to be related to several psychological and pathological processes
that can result in unsatisfactory interpersonal relationships and decreased
social adjustment. Advances in research of alexithymia require the development
and validation of assessment instruments, and its application to different
population. With this aim, we studied the psychometric properties of the Twenty
Item Toronto Alexithymia Scale (TAS-20) in Chilean population using various
modeling procedures (e.g., CFA, ESEM) in different structures (i.e., Correlated,
Unidimensional, Hierarchical or Wording factors). Among the 10 models tested, the
four-dimensional structure offered the best fit but with item-loading problems in
the last factor (Pragmatic Thinking). We suggest that the studied version of the
scale needs improvement (theoretical and empirical) to ensure optimal indices of
validation for Chilean population.
PMID- 29946288
TI - Mine, Mine, Mine: Self-Reference and Children's Retention of Novel Words.
AB - Adults demonstrate enhanced memory for words encoded as belonging to themselves
compared to those belonging to another. Known as the self-reference effect, there
is evidence for the effect in children as young as three. Toddlers are efficient
in linking novel words to novel objects, but have difficulties retaining multiple
word-object associations. The aim here was to investigate the self-reference
ownership paradigm on 3-year-old children's retention of novel words. Following
exposure to each of four novel word-object pairings, children were told that
objects either belonged to them or another character. Children demonstrated
significantly higher immediate retention of self-referenced compared to other
referenced items. Retention was also tested 4 h later and the following morning.
Retention for self- and other-referenced words was significantly higher than
chance at both delayed time points, but the difference between the self- and
other-referenced words was no longer significant. The findings suggest that when
it comes to toddlers' retention of multiple novel words there is an initial
memory enhancing effect for self- compared to other-referenced items, but the
difference diminishes over time. Children's looking times during the self
reference presentations were positively associated with retention of self
referenced words 4 h later. Looking times during the other-reference
presentations were positively associated with proportional looking at other
referenced items during immediate retention testing. The findings have
implications for children's memory for novel words and future studies could test
children's explicit memories for the ownership manipulation itself and whether
the effect is superior to other forms of memory supports such as ostensive
naming.
PMID- 29946290
TI - Choking or Delivering Under Pressure? The Case of Elimination Games in NBA
Playoffs.
AB - Neoclassical economic theories foretell that individuals exert the most effort,
and consequently produce their best performances, when the net returns to effort
are highest. We scanned through 33 NBA seasons and analyzed 1930 playoffs games
in order to test this prediction. Analysis of win probabilities in games where
one of the two teams faces elimination from the playoffs, demonstrated that the
threat of severe losses didn't lead to elevated level of performance. While
previous studies analyzed mainly single-level performance in a stable
environment, our results shed light on collective performance in a dynamic
setting. These findings can be applicable to other realms as we suggest that
managers should refrain from deliberate building of high-pressure environments
with hopes of achieving performance enhancement effect among their groups.
PMID- 29946291
TI - Affective Empathy in Behavioral Variant Frontotemporal Dementia: A Meta-Analysis.
AB - Background: Empathy deficits are a widely recognized symptom in the behavioral
variant frontotemporal dementia (bvFTD), and although several reviews have
examined cognitive empathy deficits, there are no meta-analytic studies on
affective empathy deficits. Objective: Identify salience of affective empathy in
bvFTD. Method: A thorough review of affective empathy found 139 possible studies,
but only 10 studies included measures of affective empathy and met standardized
criteria. Results: BvFTD patients demonstrated a modest impairment compared to
controls across all tasks (d = 0.98). Empathic concern as measured by the
interpersonal reactivity index was particularly effected (d = 1.12). Conclusions:
This study provides evidence for an increased commitment to observing affective
empathy in bvFTD and capturing its role in the disorder.
PMID- 29946292
TI - Carotid Artery Stenosis Contralateral to Intracranial Large Vessel Occlusion: An
Independent Predictor of Unfavorable Clinical Outcome After Mechanical
Thrombectomy.
AB - Background: Clinical outcome in patients undergoing mechanical thrombectomy (MT)
due to intracranial large vessel occlusion (LVO) in the anterior circulation is
influenced by several factors. The impact of a concomitant extracranial carotid
artery stenosis (CCAS) contralateral to the intracranial lesion remains unclear.
Methods: Retrospective analysis of 392 consecutive patients treated with MT due
to intracranial LVO in the anterior circulation in two comprehensive stroke
centers between 2014 and 2017. Clinical (including demographics and NIHSS),
imaging (including angiographic evaluation of CCAS via NASCET criteria), and
procedural data were evaluated. Primary endpoint was an unfavorable clinical
outcome defined as modified Rankin Scale 3-6 at 90 days. Results: In 27/392
patients (7%) pre-interventional imaging exhibited a CCAS (>50%) contralateral to
the intracranial lesion compared to 365 patients without relevant stenosis.
Median baseline NIHSS, procedural timings, and reperfusion success did not differ
between groups. Median volume of the final infarct core was larger in CCAS
patients (176 cm3, IQR 32-213 vs. 11 cm3, 1-65; p < 0.001). At 90 days,
unfavorable outcome was documented in 25/27 CCAS patients (93%) vs. 211/326 (65%;
p = 0.003) with a mortality of 63 vs. 19% (p = 0.001), respectively. Presence of
CCAS was associated with an unfavorable outcome at 90 days independent of age and
baseline NIHSS in multivariate logistic regression (OR 2.2, CI 1.1-4.7; p <
0.05). Conclusion: For patients undergoing MT due to intracranial vessel
occlusion in the anterior circulation, the presence of a contralateral CCAS >50%
is a predictor of unfavorable clinical outcome at 90 days.
PMID- 29946293
TI - Network Analysis in Disorders of Consciousness: Four Problems and One Proposed
Solution (Exponential Random Graph Models).
AB - In recent years, the study of the neural basis of consciousness, particularly in
the context of patients recovering from severe brain injury, has greatly
benefited from the application of sophisticated network analysis techniques to
functional brain data. Yet, current graph theoretic approaches, as employed in
the neuroimaging literature, suffer from four important shortcomings. First, they
require arbitrary fixing of the number of connections (i.e., density) across
networks which are likely to have different "natural" (i.e., stable) density
(e.g., patients vs. controls, vegetative state vs. minimally conscious state
patients). Second, when describing networks, they do not control for the fact
that many characteristics are interrelated, particularly some of the most popular
metrics employed (e.g., nodal degree, clustering coefficient)-which can lead to
spurious results. Third, in the clinical domain of disorders of consciousness,
there currently are no methods for incorporating structural connectivity in the
characterization of functional networks which clouds the interpretation of
functional differences across groups with different underlying pathology as well
as in longitudinal approaches where structural reorganization processes might be
operating. Finally, current methods do not allow assessing the dynamics of
network change over time. We present a different framework for network analysis,
based on Exponential Random Graph Models, which overcomes the above limitations
and is thus particularly well suited for clinical populations with disorders of
consciousness. We demonstrate this approach in the context of the longitudinal
study of recovery from coma. First, our data show that throughout recovery from
coma, brain graphs vary in their natural level of connectivity (from 10.4 to
14.5%), which conflicts with the standard approach of imposing arbitrary and
equal density thresholds across networks (e.g., time-points, subjects, groups).
Second, we show that failure to consider the interrelation between network
measures does lead to spurious characterization of both inter- and intra-regional
brain connectivity. Finally, we show that Separable Temporal ERGM can be employed
to describe network dynamics over time revealing the specific pattern of
formation and dissolution of connectivity that accompany recovery from coma.
PMID- 29946294
TI - Effects of Vestibular Rehabilitation in the Management of a Vestibular Migraine:
A Review.
AB - Vestibular rehabilitation (VR) has been shown to be effective for many vestibular
disorders. This review focuses on the current evidence on the effects of physical
therapy in the management of vestibular symptoms in individuals with a vestibular
migraine (VM). The individuals with a history of a migraine tend to have a high
incidence of vestibular symptoms with some or all of their headaches. A total of
six included studies investigated the effects of VR in the management of VM. The
critical review form for quantitative studies was used to appraise quality
assessment and risk of bias in the selected studies. Previous studies validated
the use of VR in the treatment of vestibular symptoms for individuals with a VM
to include improved headache and migraine-related disability in patients with a
VM. From the current evidence, it is difficult to provide conclusive evidence
regarding the efficacy of VR to minimize vestibular symptoms in patients with VM.
Therefore, more randomized controlled studies are required to make firm evidence
on the effect of VR in reducing vestibular symptoms in patients with VM. The
future prospective, blinded, randomized controlled studies may help to isolate
possible therapeutic effects of VR and other general effects.
PMID- 29946295
TI - Effects of Deep Brain Stimulation on Eye Movements and Vestibular Function.
AB - Discovery of inter-latching circuits in the basal ganglia and invention of deep
brain stimulation (DBS) for their modulation is a breakthrough in basic and
clinical neuroscience. The DBS not only changes the quality of life of hundreds
of thousands of people with intractable movement disorders, but it also offers a
unique opportunity to understand how the basal ganglia interacts with other
neural structures. An attractive yet less explored area is the study of DBS on
eye movements and vestibular function. From the clinical perspective such studies
provide valuable guidance in efficient programming of stimulation profile leading
to optimal motor outcome. From the scientific standpoint such studies offer the
ability to assess the outcomes of basal ganglia stimulation on eye movement
behavior in cognitive as well as in motor domains. Understanding the influence of
DBS on ocular motor function also leads to analogies to interpret its effects on
complex appendicular and axial motor function. This review focuses on the
influence of globus pallidus, subthalamic nucleus, and thalamus DBS on ocular
motor and vestibular functions. The anatomy and physiology of basal ganglia,
pertinent to the principles of DBS and ocular motility, is discussed.
Interpretation of the effects of electrical stimulation of the basal ganglia in
Parkinson's disease requires understanding of baseline ocular motor function in
the diseased brain. Therefore we have also discussed the baseline ocular motor
deficits in these patients and how the DBS changes such functions.
PMID- 29946296
TI - Increased Concentrations of Insulin-Like Growth Factor Binding Protein (IGFBP)-2,
IGFBP-3, and IGFBP-4 Are Associated With Fetal Mortality in Pregnant Cows.
AB - Insulin-like growth factors (IGFs) play a critical role in fetal growth, and
components of the IGF system have been associated with fetal growth restriction
in women. In human pregnancy, the proteolytic cleavage of insulin-like growth
factor binding proteins (IGFBPs), particularly IGFBP-4, releases free IGF for
respective action at the tissue level. The aim of the present study was to
determine IGFBP-2, IGFBP-3, and IGFBP-4 concentrations by Western ligand blotting
during pregnancy until day 100 in cows and to compare these concentrations with
those of non-pregnant cows and cows undergoing embryonic/fetal mortality.
Therefore, two study trials (I and II) and an in vitro study were conducted. In
study I, 43 cows were not pregnant, 34 cows were pregnant, and 4 cows were
undergoing fm. In study II, 500 cows were examined, and 7 cases of pregnancy loss
between days 24-27 and 34-37 after artificial insemination (AI, late embryonic
mortality; em) and 8 cases of pregnancy loss between days 34-37 and 54-57 after
AI (late embryonic mortality and early fetal mortality; em/fm) were defined from
the analyses of 30 pregnant and 20 non-pregnant cows randomly selected for
insulin-like growth factor 1 and IGFBP analyses. In vitro serum from pregnant (n
= 3) and non-pregnant (n = 3) cows spiked after incubation with recombinant human
(rh) IGFBP-4 for 24 h, and IGFBP-4 levels were analyzed before and after
incubation to detect proteolytic degradation. The IGFBP-2, -3, and -4
concentrations did not decline during early pregnancy in cows, while IGFBP-4
concentrations were comparable between pregnant and non-pregnant cows,
irrespective of low proteolytic activity, which was also demonstrated in cows.
Interestingly, cows with em or fm showed distinct IGFBP patterns. The IGFBP-2 and
-3 concentrations were higher (P < 0.05) in cows with fm compared to pregnant.
The IGFBP-4 levels were significantly higher in cows developing fm. Thus,
distinct differences in the circulating IGFBP concentrations could be associated
with late embryonic and early fetal losses in cattle.
PMID- 29946297
TI - Chronic Insufficient Sleep Has a Limited Impact on Circadian Rhythmicity of
Subjective Hunger and Awakening Fasted Metabolic Hormones.
AB - : Weight gain and obesity have reached epidemic proportions in modern society.
Insufficient sleep-which is also prevalent in modern society-and eating at
inappropriate circadian times have been identified as risk factors for weight
gain, yet the impact of chronic insufficient sleep on the circadian timing of
subjective hunger and physiologic metabolic outcomes are not well understood. We
investigated how chronic insufficient sleep impacts the circadian timing of
subjective hunger and fasting metabolic hormones in a 32-day in-laboratory
randomized single-blind control study, with healthy younger participants (range,
20-34 years) randomized to either Control (1:2 sleep:wake ratio, 6.67 h
sleep:13.33 h wake, n = 7, equivalent to 8 h of sleep per 24 h) or chronic sleep
restriction (CSR, 1:3.3 sleep:wake ratio, 4.67 h sleep:15.33 h wake, n = 8,
equivalent to 5.6 h of sleep per 24 h) conditions. Participants lived on a "20 h
day" designed to distribute all behaviors and food intake equally across all
phases of the circadian cycle over every six consecutive 20 h protocol days.
During each 20 h day, participants were provided a nutritionist-designed,
isocaloric diet consisting of 45-50% carbohydrate, 30-35% fat, and 15-20% protein
adjusted for sex, weight, and age. Subjective non-numeric ratings of hunger were
recorded before and after meals and fasting blood samples were taken within 5 min
of awakening. Subjective levels of hunger and fasting concentrations of leptin,
ghrelin, insulin, glucose, adiponectin, and cortisol all demonstrated circadian
patterns; there were no differences, however, between CSR and Control conditions
in subjective hunger ratings or any fasting hormone concentrations. These
findings suggest that chronic insufficient sleep may have a limited role in
altering the robust circadian profile of subjective hunger and fasted metabolic
hormones. Clinical Trial Registration: The study was registered as clinical trial
#NCT01581125.
PMID- 29946298
TI - Role of Fibroblast Growth Factor-23 in Innate Immune Responses.
AB - Fibroblast growth factor-23 (FGF-23) is a bone-derived hormone that activates
FGFR/alpha-Klotho binary complexes in the kidney renal tubules to regulate
phosphate reabsorption and vitamin D metabolism. The objective of this review is
to discuss the emerging data that show that FGF-23 has functions beyond
regulation of mineral metabolism, including roles in innate immune and
hemodynamic responses. Excess FGF-23 is associated with inflammation and adverse
infectious outcomes, as well as increased morbidity and mortality, particularly
in patients with chronic kidney disease. Enhancer elements in the FGF-23 promoter
have been identified that mediate the effects of inflammatory cytokines to
stimulate FGF-23 gene transcription in bone. In addition, inflammation induces
ectopic expression of FGF-23 and alpha-Klotho in macrophages that do not normally
express FGF-23 or its binary receptor complexes. These observations suggest that
FGF-23 may play an important role in regulating innate immunity through multiple
potential mechanisms. Circulating FGF-23 acts as a counter-regulatory hormone to
suppress 1,25D production in the proximal tubule of the kidney. Since vitamin D
deficiency may predispose infectious and cardiovascular diseases, FGF-23 effects
on innate immune responses may be due to suppression of 1,25D production.
Alternatively, systemic and locally produced FGF-23 may modulate immune functions
through direct interactions with myeloid cells, including macrophages and
polymorphonuclear leukocytes to impair immune cell functions. Short-acting small
molecules that reversibly inhibit FGF-23 offer the potential to block pro
inflammatory and cardiotoxic effects of FGF-23 with less side effects compared
with FGF-23 blocking antibodies that have the potential to cause
hyperphosphatemia and soft tissue calcifications in animal models. In conclusion,
there are several mechanisms by which FGF-23 impacts the innate immune system and
further investigation is critical for the development of therapies to treat
diseases associated with elevated FGF-23.
PMID- 29946299
TI - The Complexome of Dehalococcoides mccartyi Reveals Its Organohalide Respiration
Complex Is Modular.
AB - Dehalococcoides mccartyi strain CBDB1 is a slow growing strictly anaerobic
microorganism dependent on halogenated compounds as terminal electron acceptor
for anaerobic respiration. Indications have been described that the membrane
bound proteinaceous organohalide respiration complex of strain CBDB1 is
functional without quinone-mediated electron transfer. We here study this multi
subunit protein complex in depth in regard to participating protein subunits and
interactions between the subunits using blue native gel electrophoresis coupled
to mass spectrometric label-free protein quantification. Applying three different
solubilization modes to detach the respiration complex from the membrane we
describe different solubilization snapshots of the organohalide respiration
complex. The results demonstrate the existence of a two-subunit hydrogenase
module loosely binding to the rest of the complex, tight binding of the subunit
HupX to OmeA and OmeB, predicted to be the two subunits of a molybdopterin
binding redox subcomplex, to form a second module, and the presence of two
distinct reductive dehalogenase module variants with different sizes. In our data
we obtained biochemical evidence for the specificity between a reductive
dehalogenase RdhA (CbdbA80) and its membrane anchor protein RdhB (CbdbB3). We
also observed weak interactions between the reductive dehalogenase and the
hydrogenase module suggesting a not yet recognized contact surface between these
two modules. Especially an interaction between the two integral membrane subunits
OmeB and RdhB seems to promote the integrity of the complex. With the different
solubilization strengths we observe successive disintegration of the complex into
its subunits. The observed architecture would allow the association of different
reductive dehalogenase modules RdhA/RdhB with the other two protein complex
modules when the strain is growing on different electron acceptors. In the search
for other respiratory complexes in strain CBDB1 the remarkable result is not the
detection of a standard ATPase but the absence of any other abundant membrane
complex although an 11-subunit version of complex I (Nuo) is encoded in the
genome.
PMID- 29946300
TI - LAB Bacteriocins Controlling the Food Isolated (Drug-Resistant) Staphylococci.
AB - Staphylococci are a group of microorganisms that can be often found in processed
food and they might pose a risk for human health. In this study we have
determined the content of staphylococci in 7 different fresh goat-milk cheeses.
These bacteria were present in all of them, ranging from 103 to 106 CFU/g based
on growth on selective media. Thus, a set of 97 colonies was randomly picked for
phenotypic and genotypic identification. They could be clustered by RAPD-PCR in
10 genotypes, which were assigned by 16S rDNA sequencing to four Staphylococcus
species: Staphylococcus aureus, Staphylococcus chromogenes, S. simulans, and S.
xylosus. Representative strains of these species (n = 25) were tested for
antibiotic sensitivity, and 11 of them were resistant to at least one of the
antibiotics tested, including erythromycin, amoxicillin-clavulanic acid and
oxacillin. We also tested two bacteriocins produced by lactic acid bacteria
(LAB), namely the circular bacteriocin AS-48 and the lantibiotic nisin. These
peptides have different mechanism of action at the membrane level. Nevertheless,
both were able to inhibit staphylococci growth at low concentrations ranging
between 0.16-0.73 MUM for AS-48 and 0.02-0.23 MUM for nisin, including the
strains that displayed antibiotic resistance. The combined effect of these
bacteriocins were tested and the fractional inhibitory concentration index (FICI)
was calculated. Remarkably, upon combination, they were active at the low
micromolar range with a significant reduction of the minimal inhibitory
concentration. Our data confirms synergistic effect, either total or partial,
between AS-48 and nisin for the control of staphylococci and including antibiotic
resistant strains. Collectively, these results indicate that the combined use of
AS-48 and nisin could help controlling (pathogenic) staphylococci in food
processing and preventing antibiotic-resistant strains reaching the consumer in
the final products.
PMID- 29946301
TI - Efficient CRISPR-Cas9 Gene Disruption System in Edible-Medicinal Mushroom
Cordyceps militaris.
AB - Cordyceps militaris is a well-known edible medicinal mushroom in East Asia that
contains abundant and diverse bioactive compounds. Since traditional genome
editing systems in C. militaris were inefficient and complicated, here, we show
that the codon-optimized cas9, which was used with the newly reported promoter
Pcmlsm3 and terminator Tcmura3, was expressed. Furthermore, with the help of the
negative selection marker ura3, a CRISPR-Cas9 system that included the Cas9 DNA
endonuclease, RNA presynthesized in vitro and a single-strand DNA template
efficiently generated site-specific deletion and insertion. This is the first
report of a CRISPR-Cas9 system in C. militaris, and it could accelerate the
genome reconstruction of C. militaris to meet the need for rapid development in
the fungi industry.
PMID- 29946302
TI - Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor.
AB - Increasing evidence from recent reports of drug-resistant mycobacterial strains
poses a challenge worldwide. Drug-resistant strains often undergo mutations,
adopt alternative pathways, and express drug efflux pumps to reduce or eliminate
drug doses. Besides these intrinsic resistance mechanisms, bacteria can evade
drug doses by forming biofilms. Biofilms are the concerted growth of adherent
microorganisms, which can also be formed at the air-water interface. The growth
is supported by the extracellular polymer matrix which is self-produced by the
microorganisms. Reduced metabolic activity in a nutrient-deficient environment in
the biofilm may cause the microorganisms to take alternative pathways that can
make the microorganisms recalcitrant to the drug doses. Recent works have shown
that Mycobacterium tuberculosis expresses several proteins during its growth in
biofilm, those when deleted, did not show any effect on mycobacterial growth in
normal nutrient-sufficient conditions. Studying these unconventional proteins in
mycobacterial biofilms is therefore of utmost importance. In this article, I will
discuss one such mycobacterial biofilm-related protein FabG4 that is recently
shown to be important for mycobacterial survival in the presence of antibiotic
stressors and limited nutrient condition. In an attempt to find more effective
FabG4 inhibitors and its importance in biofilm forming M. tuberculosis, present
knowledge about FabG4 and its known inhibitors are discussed. Based on the
existing data, a putative role of FabG4 is also suggested.
PMID- 29946303
TI - Birth-and-Death Evolution and Reticulation of ITS Segments of Metschnikowia
andauensis and Metschnikowia fructicola rDNA Repeats.
AB - The internal transcribed spacer (ITS) region (ITS1, 5.8S rDNA, and ITS2)
separates the genes coding for the SSU 18S and the LSU 26S genes in the rDNA
units which are organized into long tandem arrays in the overwhelming majority of
fungi. As members of a multigenic family, these units are subject of concerted
evolution, which homogenizes their sequences. Exceptions have been observed in
certain groups of plants and in a few fungal species. In our previous study we
described exceptionally high degree of sequence diversity in the D1/D2 domains of
two pulcherrimin-producing Metschnikowia (Saccharomycotina) species which
appeared to evolve by reticulation. The major goals of this study were the
examination of the diversity of the ITS segments and their evolution. We show
that the ITS sequences of these species are not homogenized either, differ from
each other by up to 38 substitutions and indels which have dramatic effects on
the predicted secondary structures of the transcripts. The high intragenomic
diversity makes the D1/D2 domains and the ITS spacers unsuitable for barcoding of
these species and therefore the taxonomic position of strains previously assigned
to them needs revision. By analyzing the genome sequence of the M. fructicola
type strain, we also show that the rDNA of this species is fragmented, contains
pseudogenes and thus evolves by the birth-and-death mechanism rather than by
homogenisation, which is unusual in yeasts. The results of the network analysis
of the sequences further indicate that the ITS regions are also involved in
reticulation. M. andauensis and M. fructicola can form interspecies hybrids and
their hybrids segregate, providing thus possibilities for reticulation of the
rDNA repeats.
PMID- 29946304
TI - Enterocytozoon bieneusi in Minks (Neovison vison) in Northern China: A Public
Health Concern.
AB - Enterocytozoon bieneusi is the most important causative agent of microsporidiosis
and can infect almost all vertebrate and invertebrate hosts, including minks
(Neovison vison). In the present study, a total of 298 feces samples (including
79 from Heilongjiang province, 31 from Hebei province, 67 from Jilin province, 90
from Liaoning province, and 31 from Shandong province, Northern China) were
examined by nested PCR amplification of the internal transcribed spacer (ITS)
region of the rRNA gene. The overall prevalence of E. bieneusi in minks was
10.1%, with 10.5% in Jilin province, 32.3% in Hebei province, 8.9% in Liaoning
province, 0% in Shandong province, and 6.3% in Heilongjiang province.
Furthermore, multiple logistic regression analysis revealed that region was only
risk factors associated with E. bieneusi infection in the investigated minks.
Five E. bieneusi ITS genotypes (three known genotypes, namely D, Peru11, and
EbpC; two novel genotypes, namely, NCM-1 and NCM-2) were found in the current
study. Importantly, genotypes D, Peru11 and EbpC, previously identified in
humans, were also found in minks, which suggested that minks are the potential
sources of human microsporidiosis. To the best of our knowledge, this is the
first report of E. bieneusi infection in minks worldwide. The results of the
present survey have implications for the controlling E. bieneusi infection in
minks, other animals and humans.
PMID- 29946305
TI - Epidermodysplasia Verruciformis: Inborn Errors of Immunity to Human Beta
Papillomaviruses.
AB - Epidermodysplasia verruciformis (EV) is an autosomal recessive skin disorder with
a phenotype conditional on human beta-papillomavirus (beta-HPV) infection. Such
infections are common and asymptomatic in the general population, but in
individuals with EV, they lead to the development of plane wart-like and red or
brownish papules or pityriasis versicolor-like skin lesions, from childhood
onwards. Most patients develop non-melanoma skin cancer (NMSC), mostly on areas
of UV-exposed skin, from the twenties or thirties onwards. At least half of the
cases of typical EV are caused by biallelic loss-of-function mutations of
TMC6/EVER1 or TMC8/EVER2. The cellular and molecular basis of disease in TMC/EVER
deficient patients is unknown, but a defect of keratinocyte-intrinsic immunity to
beta-HPV is suspected. Indeed, these patients are not susceptible to other
infectious diseases and have apparently normal leukocyte development. In
contrast, patients with an atypical form of EV due to inborn errors of T-cell
immunity invariably develop clinical symptoms of EV in the context of other
infectious diseases. The features of the typical and atypical forms of EV thus
suggest that the control of beta-HPV infections requires both EVER1/EVER2
dependent keratinocyte-intrinsic immunity and T cell-dependent adaptive immunity.
PMID- 29946306
TI - Time Series Analysis of the Microbiota of Children Suffering From Acute
Infectious Diarrhea and Their Recovery After Treatment.
AB - Gut microbiota is closely related to acute infectious diarrhea, one of the
leading causes of mortality and morbidity in children worldwide. Understanding
the dynamics of the recovery from this disease is of clinical interest. This work
aims to correlate the dynamics of gut microbiota with the evolution of children
who were suffering from acute infectious diarrhea caused by a rotavirus, and
their recovery after the administration of a probiotic, Saccharomyces boulardii
CNCM I-745. The experiment involved 10 children with acute infectious diarrhea
caused by a rotavirus, and six healthy children, all aged between 3 and 4 years.
The children who suffered the rotavirus infection received S. boulardii CNCM I
745 twice daily for the first 5 days of the experiment. Fecal samples were
collected from each participant at 0, 3, 5, 10, and 30 days after probiotic
administration. Microbial composition was characterized by 16S rRNA gene
sequencing. Alpha and beta diversity were calculated, along with dynamical
analysis based on Taylor's law to assess the temporal stability of the
microbiota. All children infected with the rotavirus stopped having diarrhea at
day 3 after the intervention. We observed low alpha diversities in the first 5
days (p-value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic
treatment. Canonical correspondence analysis (CCA) showed differences in the gut
microbiota of healthy children and of those who suffered from acute diarrhea in
the first days (p-value < 0.05, ADONIS test), but not in the last days of the
experiment. Temporal variability was larger in children infected with the
rotavirus than in healthy ones. In particular, Gammaproteobacteria class was
found to be abundant in children with acute diarrhea. We identified the
microbiota transition from a diseased state to a healthy one with time, whose
characterization may lead to relevant clinical data. This work highlights the
importance of using time series for the study of dysbiosis related to diarrhea.
PMID- 29946307
TI - Detection of Foodborne Pathogens by Surface Enhanced Raman Spectroscopy.
AB - Food safety has become an important public health issue in both developed and
developing countries. However, as the foodborne illnesses caused by the pollution
of foodborne pathogens occurred frequently, which seriously endangered the safety
and health of human beings. More importantly, the traditional techniques, such as
PCR and enzyme-linked immunosorbent assay, are accurate and effective, but their
pretreatments are complex and time-consuming. Therefore, how to detect foodborne
pathogens quickly and sensitively has become the key to control food safety.
Because of its sensitivity, rapidity, and non-destructive damage to the sample,
the surface enhanced Raman scattering (SERS) is considered to be a powerful
testing technology that is widely used to different fields. This review aims to
give a systematic and comprehensive understanding of SERS for rapid detection of
pathogen bacteria. First, the related concepts of SERS are stated, such as its
work principal, active substrate, and biochemical origins of the detection of
bacteria by SERS. Then the latest progress and applications in food safety, from
detection and characterization of targets in label-free method to label method,
is summarized. The advantages and limitations of different SERS substrates and
methods are discussed. Finally, there are still several hurdles for the further
development of SERS techniques into real-world applications. This review comes up
with the perspectives on the future trends of the SERS technique in the field of
foodborne pathogens detection and some problems to be solved urgently. Therefore,
the purpose is mainly to understand the detection of foodborne pathogens and to
make further emphasis on the importance of SERS techniques.
PMID- 29946309
TI - Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin
Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and
Genomic Analysis.
AB - Gliotoxin (GT) is a fungal secondary metabolite that has attracted great interest
due to its high biological activity since it was discovered by the 1930s. An
inactive derivative of this molecule, bis(methylthio)gliotoxin (bmGT), has been
proposed as an invasive aspergillosis (IA) biomarker. Nevertheless, studies
regarding bmGT production among common opportunistic fungi, including the
Aspergillus genus, are scarce and sometimes discordant. As previously reported,
bmGT is produced from GT by a methyl-transferase, named as GtmA, as a negative
feedback regulatory system of GT production. In order to analyze the potential of
bmGT detection to enable identification of infections caused by different members
of the Aspergillus genus we have assessed bmGT production within the genus
Aspergillus, including A, fumigatus, A. niger, A. nidulans, and A. flavus, and
its correlation with gtmA presence. In order to validate the relevance of our in
vitro findings, we compared bmGT during in vitro culture with the presence of
bmGT in sera of patients from whom the Aspergillus spp. were isolated. Our
results indicate that most A. fumigatus isolates produce GT and bmGT both in
vitro and in vivo. In contrast, A. niger and A. nidulans were not able to produce
GT or bmGT, although A. niger produced bmGT from a exogenous GT source. The
frequency and amount of bmGT production in A. terreus and A. flavus isolates in
vitro was lower than in A. fumigatus. Our results suggest that this defect could
be related to the in vitro culture conditions, since isolates that did not
produce bmGT in vitro were able to synthetize it in vivo. In summary, our study
indicates that bmGT could be very useful to specifically detect the presence of
A. fumigatus, the most prevalent agent causing IA. Concerning A. terreus and A.
flavus a higher number of analyses from sera from infected patients will be
required to reach a useful conclusion.
PMID- 29946310
TI - Comparative Analysis of Gut Microbiota Changes in Pere David's Deer Populations
in Beijing Milu Park and Shishou, Hubei Province in China.
AB - This study used 16S rRNA high-throughput sequencing technology to examine the
differences in gut microbiota between the Pere David's deer populations in the
Beijing and Shishou areas of China in order to understand the effects of ex situ
conservation on the intestinal microflora in the Pere David's deer. Results: On
the phylum level, the main bacteria found in the Pere David's deer populations
from both areas were similar: Firmicutes and Bacteroidetes. However, the relative
abundances of the two groups were significantly different. Alpha diversity
results indicated that there was a difference in the evenness of the microflora
between the two groups, and the beta diversity results further indicated that
there was a significant difference in the microflora structure between the two
groups. Conclusions: During the ex situ conservation process of the Pere David's
deer, their food sources may change, resulting in differences in the gut
microbiota. The intestinal microflora in the Pere David's deer from the same area
are clustered. Therefore, the impact of changes in food on the gut microbiota of
the Pere David's deer should be taken into consideration during ex situ
conservation.
PMID- 29946311
TI - Effects of Estradiol and Progesterone-Induced Intracellular Calcium Fluxes on
Toxoplasma gondii Gliding, Microneme Secretion, and Egress.
AB - Research has shown that estrogen is present and plays a critical role in
vertebrate reproduction and metabolism, but the influence of steroids on
Toxoplasma gondii has received less attention. Our data showed that estradiol and
progesterone induced parasitic cytosolic Ca2+ fluxes. This process required
estrogen to enter the cytoplasm of T. gondii, and cGMP-dependent protein kinase G
(PKG) and phosphoinositide-phospholipase C (PI-PLC) emerged as important factors
controlling parasitic intracellular (IC) Ca2+ signals. Cytosolic Ca2+, which is
regulated by estradiol, was mostly mobilized from acidic organelles. Moreover,
cytosolic Ca2+ slightly increased MIC2 protein secretion and promoted the gliding
motility and egress of parasites, thus enhancing the pathogenicity of T. gondii,
as shown in our previous research. We subsequently determined that the main
source of Ca2+ regulated by progesterone was a neutral store. In contrast to the
findings of estradiol, progesterone reduced MIC2 protein secretion and inhibited
the gliding motility of parasites, which may decrease their pathogenicity.
Additionally, unlike in mammals, estradiol and progesterone had no effect on
nitric oxide (NO) or reactive oxygen species (ROS) production in T. gondii.
PMID- 29946308
TI - Mechanistic Insights in the Success of Fecal Microbiota Transplants for the
Treatment of Clostridium difficile Infections.
AB - Fecal microbiota transplantation has proven to be an effective treatment for
infections with the gram-positive enteropathogen Clostridium difficile. Despite
its effectiveness, the exact mechanisms that underlie its success are largely
unclear. In this review, we highlight the pleiotropic effectors that are
transferred during fecal microbiota transfer and relate this to the C. difficile
lifecycle. In doing so, we show that it is likely that multiple factors
contribute to the elimination of symptoms of C. difficile infections after fecal
microbiota transplantation.
PMID- 29946312
TI - Streptomyces spp. From Ethiopia Producing Antimicrobial Compounds:
Characterization via Bioassays, Genome Analyses, and Mass Spectrometry.
AB - A total of 416 actinomycete cultures were isolated from various unique
environments in Ethiopia and tested for bioactivity. Six isolates with pronounced
antimicrobial activity were chosen for taxonomic identification and further
investigation. Morphological and cultural properties of the isolates were found
to be consistent with those of the genus Streptomyces, which was further
confirmed by phylogenetic analysis based on 16S rRNA gene sequences. One of the
isolates, designated Streptomyces sp. Go-475, which displayed potent activity
against both pathogenic yeasts and Gram-positive bacteria, was chosen for further
investigation. Metabolite profiles and bioactivity of Go-475 incubated on wheat
bran-based solid and soya flour-based liquid media were compared using high
resolution LC-MS. This allowed identification of several known compounds, and
suggested the ability of Go-475 to produce new secondary metabolites. Major anti
bacterial compounds were purified from liquid cultures of Go-475, and their
structures elucidated by NMR and HRMS as 8-O-methyltetrangomycin and 8-O
methyltetrangulol. In addition, many potentially novel metabolites were detected,
the majority of which were produced in solid media-based fermentation. The genome
sequence of Streptomyces sp. Go-475 was obtained using a hybrid assembly approach
of high quality Illumina short read and low quality Oxford Nanopore long read
data. The complete linear chromosome of 8,570,609 bp, featuring a G+C content of
71.96%, contains 7,571 predicted coding sequences, 83 t(m)RNA genes, and six rrn
operons. Analysis of the genome for secondary metabolite biosynthesis gene
clusters further confirmed potential of this isolate to synthesize chemically
diverse natural products, and allowed to connect certain clusters with
experimentally confirmed molecules.
PMID- 29946313
TI - Sporothrix schenckii Immunization, but Not Infection, Induces Protective Th17
Responses Mediated by Circulating Memory CD4+ T Cells.
AB - Sporotrichosis is a chronic subcutaneous mycosis caused by the Sporothrix
schenckii species complex and it is considered an emerging opportunistic
infection in countries with tropical and subtropical climates. The host's immune
response has a main role in the development of this disease. However, it is
unknown the features of the memory cellular immune response that could protect
against the infection. Our results show that i.d. immunization in the ears of
mice with inactivated S. schenckii conidia (iC) combined with the cholera toxin
(CT) induces a cellular immune response mediated by circulating memory CD4+ T
cells, which mainly produce interleukin 17 (IL-17). These cells mediate a strong
delayed-type hypersensitivity (DTH) reaction. Systemic and local protection
against S. schenckii was mediated by circulating CD4+ T cells. In contrast, the
infection induces a potent immune response in the skin mediated by CD4+ T cells,
which have an effector phenotype that preferentially produce interferon gamma
(IFN-gamma) and mediate a transitory DTH reaction. Our findings prove the
potential value of the CT as a potent skin adjuvant when combined with fungal
antigens, and they also have important implications for our better understanding
of the differences between the memory immune response induced by the skin
immunization and those induced by the infection; this knowledge enhances our
understanding of how a protective immune response against a S. schenckii
infection is developed.
PMID- 29946314
TI - Oenococcus oeni Exopolysaccharide Biosynthesis, a Tool to Improve Malolactic
Starter Performance.
AB - Oenococcus oeni is the lactic acid bacterium that most commonly drives malolactic
fermentation (MLF) in wine. Though the importance of MLF in terms of wine
microbial stability and sensory improvement is well established, it remains a
winemaking step not so easy to control. O. oeni displays many adaptation tools to
resist the harsh wine conditions which explain its natural dominance at this
stage of winemaking. Previous findings showed that capsular polysaccharides and
endogenous produced dextran increased the survival rate and the conservation time
of malolactic starters. In this paper, we showed that exopolysaccharides specific
production rates were increased in the presence of single stressors relevant to
wine (pH, ethanol). The transcription of the associated genes was investigated in
distinct O. oeni strains. The conditions in which eps genes and EPS synthesis
were most stimulated were then evaluated for the production of freeze dried
malolactic starters, for acclimation procedures and for MLF efficiency. Sensory
analysis tests on the resulting wines were finally performed.
PMID- 29946315
TI - Acinetobacter baumannii: Epidemiological and Beta-Lactamase Data From Two
Tertiary Academic Hospitals in Tshwane, South Africa.
AB - Acinetobacter baumannii is an opportunistic pathogen that is increasingly
responsible for hospital-acquired infections. The increasing prevalence of
carbapenem resistant A. baumannii has left clinicians with limited treatment
options. Last line antimicrobials (i.e., polymyxins and glycylcyclines) are often
used as treatment options. The aim of this study was to determine the prevalence
of selected beta-lactamase genes from A. baumannii isolates obtained from
patients with hospital-acquired infections and to determine the genetic
relationship and epidemiological profiles among clinical A. baumannii isolates
collected from two tertiary academic hospitals in the Tshwane region, South
Africa (SA). Multiplex-PCR (M-PCR) assays were performed to detect selected
resistance genes. The collected isolates' genetic relatedness was determined by
using pulsed field gel electrophoresis (PFGE) and multilocus sequence typing
(MLST). The acquired oxacillinase (OXA) genes, notably blaOXA-23-like were
prevalent in the A. baumannii isolates. The M-PCR assays showed that the isolates
collected from hospital A contained the OXA-23-like (96%; n = 69/72) genes and
the isolates collected from hospital B contained the OXA-23-like (91%; n = 63/69)
and OXA-58-like (4%; n = 3/69) genes. Colistin resistance was found in 1% of the
isolates (n = 2/141) and tigecycline intermediate resistance was found in 6% of
the isolates (n = 8/141). The A. baumannii isolates were genetically diverse.
Molecular epidemiological data showed that specific sequence types (STs) (ST106,
ST229, ST258 and ST208) were established in both hospitals, while ST848 was
established in hospital A and ST502, ST339 and the novel ST1552 were established
in hospital B. ST848 (established in hospital A) was predominately detected in
ICU wards whereas ST208, ST339 and the novel ST1552 (established in hospital B)
were detected in ICUs and the general wards. The origin of the A. baumannii
isolates in the hospitals may be due to the dissemination and adaptation of a
diverse group of successful clones. Poor infection control and prevention
strategies and possibly the overuse of antimicrobials contributed to the
establishment of these A. baumannii clones in the studied hospitals.
PMID- 29946316
TI - The BCGDeltaBCG1419c Vaccine Candidate Reduces Lung Pathology, IL-6, TNF-alpha,
and IL-10 During Chronic TB Infection.
AB - Mycobacterium tuberculosis (M. tuberculosis), the causative agent of human
tuberculosis (TB), is estimated to be harbored by up to 2 billion people in a
latent TB infection (LTBI) state. The only TB vaccine approved for use in humans,
BCG, does not confer protection against establishment of or reactivation from
LTBI, so new vaccine candidates are needed to specifically address this need.
Following the hypothesis that mycobacterial biofilms resemble aspects of LTBI, we
modified BCG by deleting the BCG1419c gene to create the BCGDeltaBCG1419c vaccine
strain. In this study, we compared cytokine profiles, bacterial burden, and lung
lesions after immunization with BCG or BCGDeltaBCG1419c before and after 6 months
of aerosol infection with M. tuberculosis H37Rv in the resistant C57BL/6 mouse
model. Our results show that in infected mice, BCGDeltaBCG1419c significantly
reduced lung lesions and IL-6 in comparison to the unmodified BCG strain, and was
the only vaccine that decreased production of TNF-alpha and IL-10 compared to non
vaccinated mice, while vaccination with BCG or BCGDeltaBCG1419c significantly
reduced IFN-gamma production. Moreover, transcriptome profiling of
BCGDeltaBCG1419c suggests that compared to BCG, it has decreased expression of
genes involved in mycolic acids (MAs) metabolism, and antigenic chaperones, which
might be involved in reduced pathology compared to BCG-vaccinated mice.
PMID- 29946317
TI - The C-Type Lectin Receptor DC-SIGN Has an Anti-Inflammatory Role in Human M(IL-4)
Macrophages in Response to Mycobacterium tuberculosis.
AB - DC-SIGN (CD209/CLEC4L) is a C-type lectin receptor (CLR) that serves as a
reliable cell-surface marker of interleukin 4 (IL-4)-activated human macrophages
[M(IL-4)], which historically represent the most studied subset within the M2
spectrum of macrophage activation. Although DC-SIGN plays important roles in
Mycobacterium tuberculosis (Mtb) interactions with dendritic cells, its
contribution to the Mtb-macrophage interaction remains poorly understood. Since
high levels of IL-4 are correlated with tuberculosis (TB) susceptibility and
progression, we investigated the role of DC-SIGN in M(IL-4) macrophages in the TB
context. First, we demonstrate that DC-SIGN expression is present both in CD68+
macrophages found in tuberculous pulmonary lesions of non-human primates, and in
the CD14+ cell population isolated from pleural effusions obtained from TB
patients (TB-PE). Likewise, we show that DC-SIGN expression is accentuated in
M(IL-4) macrophages derived from peripheral blood CD14+ monocytes isolated from
TB patients, or in macrophages stimulated with acellular TB-PE, arguing for the
pertinence of DC-SIGN-expressing macrophages in TB. Second, using a siRNA
mediated gene silencing approach, we performed a transcriptomic analysis of DC
SIGN-depleted M(IL-4) macrophages and revealed the upregulation of pro
inflammatory signals in response to challenge with Mtb, as compared to control
cells. This pro-inflammatory gene signature was confirmed by RT-qPCR,
cytokine/chemokine-based protein array, and ELISA analyses. We also found that
inactivation of DC-SIGN renders M(IL-4) macrophages less permissive to Mtb
intracellular growth compared to control cells, despite the equal level of
bacteria uptake. Last, at the molecular level, we show that DC-SIGN interferes
negatively with the pro-inflammatory response and control of Mtb intracellular
growth mediated by another CLR, Dectin-1 (CLEC7A). Collectively, this study
highlights a dual role for DC-SIGN as, on the one hand, being a host factor
granting advantage for Mtb to parasitize macrophages and, on the other hand,
representing a molecular switch to turn off the pro-inflammatory response in
these cells to prevent potential immunopathology associated to TB.
PMID- 29946318
TI - Immune Targeting of Tetraspanins Involved in Cell Invasion and Metastasis.
AB - Metastasis is the ultimate consequence of cancer progression and the cause of
patients' death across different cancer types. Patients with initial diagnosis of
distant disease have a worst 5-year survival compared to patients with localized
disease. Therapies that target primary tumors fail to eradicate distant
dissemination of cancer. Recently, immunotherapies have improved the survival of
patients with metastatic disease, such as melanoma and lung cancer. However, only
a fraction of patients responds to immunotherapy modalities that target the host
immune system. The need to identify new druggable targets that inhibit or prevent
metastasis is, therefore, much needed. Tetraspanins have emerged as key players
in regulating cell migration, invasion, and metastasis. By serving as molecular
adaptors that cluster adhesion receptors, signaling molecules, and cell surface
receptors; tetraspanins are involved in all steps of the metastatic cascade. They
regulate cell proliferation, participate in EMT transition, modulate integrin
mediated cell adhesion, and participate in angiogenesis and invasion processes.
Tetraspanins have also been shown to modulate metastasis indirectly through
exosomes and by regulating cellular interactions in the immune system.
Importantly, targeting individual tetraspanin with antibodies has impacted tumor
progression. This review will focus on the contribution of tetraspanins to the
metastatic process and their potential as therapeutic tumor targets.
PMID- 29946319
TI - Resolvin E1 Promotes Bone Preservation Under Inflammatory Conditions.
AB - Resolvins are endogenous lipid mediators derived from omega-3 fatty acids.
Resolvin E1 (RvE1), derived from eicosapentaenoic acid (EPA), modulates
osteoclasts and immune cells in periodontal disease models. The direct role of
RvE1 in bone remodeling is not well understood. The objective of this study was
to determine the impact of RvE1 on bone remodeling under inflammatory conditions.
Our working hypothesis is that RvE1 downregulates bone resorption through direct
actions on both osteoblast and osteoclast function in inflammatory
osteoclastogenesis. A tumor necrosis factor-alpha induced local calvarial
osteolysis model with or without the systemic administration of RvE1 was used. To
evaluate osteoclastogenesis and NFkappaB signaling pathway activity, murine bone
tissue was evaluated by Micro CT (MUCT) analysis, TRAP staining, and
immunofluorescence analysis. Mechanistically, to evaluate the direct role of RvE1
impacting bone cells, primary calvarial mouse osteoblasts were stimulated with
interleukin (IL)-6 (10 ng/ml) and IL-6 receptor (10 ng/ml) and simultaneously
incubated with or without RvE1 (100 nM). Expression of receptor activator of
NFkappaB ligand (RANKL) and osteoprotegerin (OPG) was measured by ELISA. RNA
sequencing (RNA-Seq) and differential expression analysis was performed to
determine signaling pathways impacted by RvE1. The systemic administration of
RvE1 reduced calvarial bone resorption as determined by uCT. Histologic analysis
of calvaria revealed that osteoclastogenesis was reduced as determined by number
and size of osteoclasts in TRAP-stained sections (p < 0.05). Immunofluorescence
staining of calvarial sections revealed that RvE1 reduced RANKL secretion by 25%
(p < 0.05). Stimulation of osteoblasts with IL-6 increased RANKL production by
30% changing the RANKL/OPG to favor osteoclast activation and bone resorption.
The ratio changes were reversed by 100 nM RvE1. RvE1 decreased the production of
RANKL maintaining an RANKL/OPG more favorable for bone formation. RNA-Seq and
transcriptomic pipeline analysis revealed that RvE1 significantly downregulates
osteoclast differentiation mediated by differential regulation of NFkappaB and
PI3K-AKT pathways. RvE1 reduces inflammatory bone resorption. This action is
mediated, at least in part, by direct actions on bone cells promoting a favorable
RANKL/OPG ratio. Mediators of resolution in innate immunity also directly
regulate bone cell gene expression that is modulated by RvE1 through at least 14
specific genes in this mouse model.
PMID- 29946320
TI - Natural Autoantibodies: An Undersugn Hero of the Immune System and Autoimmune
Disorders-A Point of View.
PMID- 29946322
TI - The Transcription Factor NFATc1 Supports the Rejection of Heterotopic Heart
Allografts.
AB - The immune suppressants cyclosporin A (CsA) and tacrolimus (FK506) are used
worldwide in transplantation medicine to suppress graft rejection. Both CsA and
FK506 inhibit the phosphatase calcineurin (CN) whose activity controls the immune
receptor-mediated activation of lymphocytes. Downstream targets of CN in
lymphocytes are the nuclear factors of activated T cells (NFATs). We show here
that the activity of NFATc1, the most prominent NFAT factor in activated
lymphocytes supports the acute rejection of heterotopic heart allografts. While
ablation of NFATc1 in T cells prevented graft rejection, ectopic expression of
inducible NFATc1/alphaA isoform led to rejection of heart allografts in recipient
mice. Acceptance of transplanted hearts in mice bearing NFATc1-deficient T cells
was accompanied by a reduction in number and cytotoxicity of graft infiltrating
cells. In CD8+ T cells, NFATc1 controls numerous intracellular signaling pathways
that lead to the metabolic switch to aerobic glycolysis and the expression of
numerous lymphokines, chemokines, and their receptors, including Cxcr3 that
supports the rejection of allogeneic heart transplants. These findings favors
NFATc1 as a molecular target for the development of new strategies to control the
cytotoxicity of T cells upon organ transplantation.
PMID- 29946321
TI - Glucocorticoids, Sex Hormones, and Immunity.
AB - Glucocorticoid hormones regulate essential body functions in mammals, control
cell metabolism, growth, differentiation, and apoptosis. Importantly, they are
potent suppressors of inflammation, and multiple immune-modulatory mechanisms
involving leukocyte apoptosis, differentiation, and cytokine production have been
described. Due to their potent anti-inflammatory and immune-suppressive activity,
synthetic glucocorticoids (GCs) are the most prescribed drugs used for treatment
of autoimmune and inflammatory diseases. It is long been noted that males and
females exhibit differences in the prevalence in several autoimmune diseases
(AD). This can be due to the role of sexual hormones in regulation of the immune
responses, acting through their endogenous nuclear receptors to mediate gene
expression and generate unique gender-specific cellular environments. Given the
fact that GCs are the primary physiological anti-inflammatory hormones, and that
sex hormones may also exert immune-modulatory functions, the link between GCs and
sex hormones may exist. Understanding the nature of this possible crosstalk is
important to unravel the reason of sexual disparity in AD and to carefully
prescribe these drugs for the treatment of inflammatory diseases. In this review,
we discuss similarities and differences between the effects of sex hormones and
GCs on the immune system, to highlight possible axes of functional interaction.
PMID- 29946323
TI - Dissociation of C-Reactive Protein Localizes and Amplifies Inflammation: Evidence
for a Direct Biological Role of C-Reactive Protein and Its Conformational
Changes.
AB - C-reactive protein (CRP) is a member of the pentraxin superfamily that is widely
recognized as a marker of inflammatory reactions and cardiovascular risk in
humans. Recently, a growing body of data is emerging, which demonstrates that CRP
is not only a marker of inflammation but also acts as a direct mediator of
inflammatory reactions and the innate immune response. Here, we critically review
the various lines of evidence supporting the concept of a pro-inflammatory "CRP
system." The CRP system consists of a functionally inert circulating pentameric
form (pCRP), which is transformed to its highly pro-inflammatory structural
isoforms, pCRP* and ultimately to monomeric CRP (mCRP). While retaining an
overall pentameric structure, pCRP* is structurally more relaxed than pCRP, thus
exposing neoepitopes important for immune activation and complement fixation.
Thereby, pCRP* shares its pro-inflammatory properties with the fully dissociated
structural isoform mCRP. The dissociation of pCRP into its pro-inflammatory
structural isoforms and thus activation of the CRP system occur on necrotic,
apoptotic, and ischemic cells, regular beta-sheet structures such as beta
amyloid, the membranes of activated cells (e.g., platelets, monocytes, and
endothelial cells), and/or the surface of microparticles, the latter by binding
to phosphocholine. Both pCRP* and mCRP can cause activation of platelets,
leukocytes, endothelial cells, and complement. The localization and deposition of
these pro-inflammatory structural isoforms of CRP in inflamed tissue appear to be
important mediators for a range of clinical conditions, including
ischemia/reperfusion (I/R) injury of various organs, cardiovascular disease,
transplant rejection, Alzheimer's disease, and age-related macular degeneration.
These findings provide the impetus to tackle the vexing problem of innate
immunity response by targeting CRP. Understanding the "activation process" of CRP
will also likely allow the development of novel anti-inflammatory drugs, thereby
providing potential new immunomodulatory therapeutics in a broad range of
inflammatory diseases.
PMID- 29946324
TI - Association Genetics in Populus Reveal the Allelic Interactions of Pto-MIR167a
and Its Targets in Wood Formation.
AB - MicroRNAs (miRNAs) play crucial regulatory roles in plant growth and development
by interacting with RNA molecules, including messenger RNAs (mRNAs) and long non
coding RNAs (lncRNAs); however, the genetic networks of miRNAs and their targets
influencing the phenotypes of perennial trees remain to be investigated. Here, we
integrated expression profiling and association analysis of underlying physiology
and expression traits to dissect the allelic variations and genetic interactions
of Pto-MIR167a and its targets, sponge lncRNA ARFRL, and Pto-ARF8, in 435
unrelated individuals of Populus tomentosa. Tissue-specific expression analysis
in eight tissues, including stem, leaf, root, and shoot apex, revealed negative
correlations between Pto-MIR167a and lncRNA ARFRL and Pto-ARF8 (r = -0.60 and
0.61, respectively, P < 0.01), and a positive correlation between sponge lncRNA
ARFRL and Pto-ARF8 (r = 0.90, P < 0.01), indicating their potential regulatory
roles in tree growth and wood formation. Single nucleotide polymorphism (SNP)
based association studies detected 53 significant associations (P < 0.01, Q <
0.1) representing 41 unique SNPs from the three genes and six traits, suggesting
their potential roles in wood formation. Epistasis uncovered 88 pairwise
interactions for 10 traits, which provided substantial evidence for genetic
interactions among Pto-MIR167a, lncRNA ARFRL, and Pto-ARF8. Using gene expression
based association mapping, we also examined SNPs within the three genes that
influence phenotypes by regulating the expression of Pto-ARF8. Interestingly,
SNPs in the precursor region of Pto-MIR167a altered its secondary structure
stability and transcription, thereby affecting the expression of its targets. In
summary, we elucidated the genetic interactions between Pto-MIR167a and its
targets, sponge lncRNA ARFRL, and Pto-ARF8, in tree growth and wood formation,
and provide a feasible method for further investigation of multi-factor genetic
networks influencing phenotypic variation in the population genetics of trees.
PMID- 29946325
TI - VIP1 and Its Homologs Are Not Required for Agrobacterium-Mediated Transformation,
but Play a Role in Botrytis and Salt Stress Responses.
AB - The bZIP transcription factor VIP1 interacts with the Agrobacterium virulence
protein VirE2, but the role of VIP1 in Agrobacterium-mediated transformation
remains controversial. Previously tested vip1-1 mutant plants produce a truncated
protein containing the crucial bZIP DNA-binding domain. We generated the
CRISPR/Cas mutant vip1-2 that lacks this domain. The transformation
susceptibility of vip1-2 and wild-type plants is similar. Because of potential
functional redundancy among VIP1 homologs, we tested transgenic lines expressing
VIP1 fused to a SRDX repression domain. All VIP1-SRDX transgenic lines showed
wild-type levels of transformation, indicating that neither VIP1 nor its homologs
are required for Agrobacterium-mediated transformation. Because VIP1 is involved
in innate immune response signaling, we tested the susceptibility of vip1 mutant
and VIP1-SRDX plants to Pseudomonas syringae and Botrytis cinerea. vip1 mutant
and VIP1-SRDX plants show increased susceptibility to B. cinerea but not to P.
syringae infection, suggesting a role for VIP1 in B. cinerea, but not in P.
syringae, defense signaling. B. cinerea susceptibility is dependent on abscisic
acid (ABA) which is also important for abiotic stress responses. The germination
of vip1 mutant and VIP1-SRDX seeds is sensitive to exogenous ABA, suggesting a
role for VIP1 in response to ABA. vip1 mutant and VIP1-SRDX plants show increased
tolerance to growth in salt, indicating a role for VIP1 in response to salt
stress.
PMID- 29946326
TI - Elicitor-Based Biostimulant PSP1 Protects Soybean Against Late Season Diseases in
Field Trials.
AB - Currently, fungicide application in soybean production accounts for an important
amount of global pesticide use, and it is therefore most desirable to find new
healthier and more environmental friendly alternatives for the phytosanitary
management in this crop. In this study, we present convincing evidence for
effective induction of disease protection by the agricultural biostimulant PSP1,
a formulation based on the plant-defense eliciting activity of the fungal
protease AsES (Acremonium strictum elicitor subtilisin), in multiple field trials
in Argentina. PSP1 was shown to combine well with commercial spray adjuvants, an
insecticide, a herbicide and fungicides used in Argentinian soybean production
without losing any defense-inducing activity, indicating an easy and efficient
adaptability to conventional soybean production and disease management in the
region. Results from multiple soybean field trials conducted with different elite
genotypes at several locations during two consecutive growing seasons, showed
that PSP1 is able to induce an enhanced pathogen defense which effectively
reduced late season disease (LSD) development in field-grown soybean. This
defense response seems to be broad-range as disease development was clearly
reduced for at least three different fungi causing LSDs in soybean (Septoria
glycines, Cercospora kikuchii and Cercospora sojina). It was noteworthy that
application of PSP1 in soybean alone gave a similar protection against fungal
diseases as compared to the commercial fungicides included in the field trials
and that PSP1 applied together with a fungicide at reproductive stages enhanced
disease protection and significantly increased grain yields. PSP1 is the first
example of an elicitor-based strategy in order to efficiently control multiple
fungal diseases under field conditions in the soybean crop. These results show
the feasibility of using induced resistance products as complements or even full
good replacements to currently used chemical pesticides, fulfilling a role as
important components of a more sustainable crop disease management system.
PMID- 29946327
TI - O3-Induced Leaf Senescence in Tomato Plants Is Ethylene Signaling-Dependent and
Enhances the Population Abundance of Bemisia tabaci.
AB - Elevated ozone (O3) can alter the phenotypes of host plants particularly in
induction of leaf senescence, but few reports examine the involvement of
phytohormone in O3-induced changes in host phenotypes that influence the foraging
quality for insects. Here, we used an ethylene (ET) receptor mutant Nr and its
wild-type to determine the function of the ET signaling pathway in O3-induced
leaf senescence, and bottom-up effects on the performance of Bemisia tabaci in
field open-top chambers (OTCs). Our results showed that elevated O3 reduced
photosynthetic efficiency and chlorophyll content and induced leaf senescence of
plant regardless of plant genotype. Leaf senescence in Nr plants was alleviated
relative to wild-type under elevated O3. Further analyses of foliar quality
showed that elevated O3 had little effect on phytohormone-mediated defenses, but
significantly increased the concentration of amino acids in two plant genotypes.
Furthermore, Nr plants had lower amino acid content relative to wild-type under
elevated O3. These results provided an explanation of O3-induced increase in
abundance of B. tabaci. We concluded that O3-induced senescence of plant was ET
signal-dependent, and positive effects of O3-induced leaf senescence on the
performance of B. tabaci largely resulted from changes of nutritional quality of
host plants.
PMID- 29946329
TI - High-Throughput Analysis of Arabidopsis Stem Vibrations to Identify Mutants With
Altered Mechanical Properties.
AB - Mechanical properties are rarely used as quantitative indices for the large-scale
mutant screening of plants, even in the model plant Arabidopsis thaliana. The
mechanical properties of plant stems generally influence their vibrational
characteristics. Here, we developed Python-based software, named AraVib, for the
high-throughput analysis of free vibrations of plant stems, focusing specifically
on Arabidopsis stem vibrations, and its extended version, named AraVibS, to
identify mutants with altered mechanical properties. These programs can be used
without knowledge of Python and require only an inexpensive handmade setting
stand and an iPhone/iPad with a high-speed shooting function for data
acquisition. Using our system, we identified an nst1 nst3 double-mutant lacking
secondary cell walls in fiber cells and a wrky12 mutant displaying ectopic
formation of secondary cell wall compared with wild type by employing only two
growth traits (stem height and fresh weight) in addition to videos of stem
vibrations. Furthermore, we calculated the logarithmic decrement, the damping
ratio, the natural frequency and the stiffness based on the spring-mass-damper
model from the video data using AraVib. The stiffness was estimated to be
drastically decreased in nst1 nst3, which agreed with previous tensile test
results. However, in wrky12, the stiffness was significantly increased. These
results demonstrate the effectiveness of our new system. Because our method can
be applied in a high-throughput manner, it can be used to screen for mutants with
altered mechanical properties.
PMID- 29946328
TI - Prioritization of Candidate Genes in QTL Regions for Physiological and
Biochemical Traits Underlying Drought Response in Barley (Hordeum vulgare L.).
AB - Drought is one of the most adverse abiotic factors limiting growth and
productivity of crops. Among them is barley, ranked fourth cereal worldwide in
terms of harvested acreage and production. Plants have evolved various mechanisms
to cope with water deficit at different biological levels, but there is an
enormous challenge to decipher genes responsible for particular complex
phenotypic traits, in order to develop drought tolerant crops. This work presents
a comprehensive approach for elucidation of molecular mechanisms of drought
tolerance in barley at the seedling stage of development. The study includes
mapping of QTLs for physiological and biochemical traits associated with drought
tolerance on a high-density function map, projection of QTL confidence intervals
on barley physical map, and the retrievement of positional candidate genes (CGs),
followed by their prioritization based on Gene Ontology (GO) enrichment analysis.
A total of 64 QTLs for 25 physiological and biochemical traits that describe
plant water status, photosynthetic efficiency, osmoprotectant and hormone
content, as well as antioxidant activity, were positioned on a consensus map,
constructed using RIL populations developed from the crosses between European and
Syrian genotypes. The map contained a total of 875 SNP, SSR and CGs, spanning
941.86 cM with resolution of 1.1 cM. For the first time, QTLs for ethylene,
glucose, sucrose, maltose, raffinose, alpha-tocopherol, gamma-tocotrienol
content, and catalase activity, have been mapped in barley. Based on overlapping
confidence intervals of QTLs, 11 hotspots were identified that enclosed more than
60% of mapped QTLs. Genetic and physical map integration allowed the
identification of 1,101 positional CGs within the confidence intervals of drought
response-specific QTLs. Prioritization resulted in the designation of 143 CGs,
among them were genes encoding antioxidants, carboxylic acid biosynthesis
enzymes, heat shock proteins, small auxin up-regulated RNAs, nitric oxide
synthase, ATP sulfurylases, and proteins involved in regulation of flowering
time. This global approach may be proposed for identification of new CGs that
underlies QTLs responsible for complex traits.
PMID- 29946331
TI - Elucidation of Characteristic Sulfur-Fumigated Markers and Chemical
Transformation Mechanism for Quality Control of Achyranthes bidentate Blume Using
Metabolome and Sulfur Dioxide Residue Analysis.
AB - Achyranthes bidentata Blume (AB) is a health food and a sulfur-free herbal
medicine that is one of the most heavily sulfur-fumigated herbs in the
marketplace. In this work, a comprehensive approach using ultra-performance
liquid chromatography coupled with quadrupole time-of-flight-MS (UPLC-Q-TOF-MS)
and multivariate statistical analysis was developed to identify characteristic
sulfur-fumigation markers, elucidate chemical transformation mechanisms and
characterize the degree of sulfur-fumigation of AB. Non-fumigated and sulfur
fumigated AB samples were compared by UPLC-Q-TOF-MS/MS analysis. Three triterpene
saponins (Betavulgarosides II-IV) and two amides (Feruloyl-4-O-methyldopamine and
Moupinamide) were identified as characteristic markers, which were positively
correlated with two active AB components, namely oleanic acid and ferulic acid,
respectively. Moreover, the extent of the sulfur-fumigation under different
weight ratios of sulfur to herbal materials (1:20, 1:40, and 1:80) was analyzed
based on chemical transformations and sulfur dioxide residues. Further
verification showed that the ratio of 1:40 within 1 h was reasonable and
efficient for herb quality preservation and assurance. This study provides a
reliable sulfur-fumigation protocol for the quality control of AB and other
herbs.
PMID- 29946330
TI - Identification and Phenotypic Characterization of ZEBRA LEAF16 Encoding a beta
Hydroxyacyl-ACP Dehydratase in Rice.
AB - The chloroplast is a self-independent organelle and contains its own
transcription and translation systems. The establishment of genetic systems is
vital for normal plant growth and development. We isolated a rice zebra leaf 16
(zl16) mutant derived from rice cultivar 9311. The zl16 mutant showed chlorotic
abnormalities in the transverse sectors of the young leaves of seedlings. The use
of transmission electron microscopy (TEM) demonstrated that dramatic defects
occurred in variegated zl16 leaves during the early development of a chloroplast.
Map-based cloning revealed that ZL16 encodes a beta-hydroxyacyl-ACP dehydratase
(HAD) involved in de novo fatty acid synthesis. Compared with the wild type, a
missense mutation (Arg164Trp) in the zl16 mutant was identified, which
significantly reduced enzymatic activity and altered the three-dimensional
modeling structure of the putative protein. ZL16 was ubiquitously expressed in
various plant organs, with a pronounced level in the young leaf. A subcellular
localization experiment indicated that ZL16 was targeted in the chloroplast.
Furthermore, we analyzed the expression of some nuclear genes involved in
chloroplast development, and found they were altered in the zl16 mutant. RNA-Seq
analysis indicated that some genes related to cell membrane constituents were
downregulated in the mutant. An in vivo metabolic assay revealed that the total
fatty acid content in the mutant was significantly decreased relative to the wild
type. Our results indicate that HAD is essential for the development of
chloroplasts by regulating the synthesis of fatty acids in rice.
PMID- 29946332
TI - Genome-Wide Exon-Capture Approach Identifies Genetic Variants of Norway Spruce
Genes Associated With Susceptibility to Heterobasidion parviporum Infection.
AB - Root and butt rot caused by members of the Heterobasidion annosum species complex
is the most economically important disease of conifer trees in boreal forests.
Wood decay in the infected trees dramatically decreases their value and causes
considerable losses to forest owners. Trees vary in their susceptibility to
Heterobasidion infection, but the genetic determinants underlying the variation
in the susceptibility are not well-understood. We performed the identification of
Norway spruce genes associated with the resistance to Heterobasidion parviporum
infection using genome-wide exon-capture approach. Sixty-four clonal Norway
spruce lines were phenotyped, and their responses to H. parviporum inoculation
were determined by lesion length measurements. Afterwards, the spruce lines were
genotyped by targeted resequencing and identification of genetic variants (SNPs).
Genome-wide association analysis identified 10 SNPs located within 8 genes as
significantly associated with the larger necrotic lesions in response to H.
parviporum inoculation. The genetic variants identified in our analysis are
potential marker candidates for future screening programs aiming at the
differentiation of disease-susceptible and resistant trees.
PMID- 29946333
TI - An Integration of Genome-Wide Association Study and Gene Co-expression Network
Analysis Identifies Candidate Genes of Stem Lodging-Related Traits in Brassica
napus.
AB - Lodging is a persistent problem which severely reduce yield and impair seed
quality in rapeseed (Brassica napus L.). Enhancing stem strength (SS) has proven
to be an effective approach to decrease lodging risk. In the present study, four
interrelated stem lodging-related traits, including stem breaking resistance
(SBR), stem diameter (SD), SS, and lodging coefficient (LC), were investigated
among 472 rapeseed accessions. A genome-wide association study (GWAS) using
Brassica 60K SNP array for stem lodging-related traits identified 67
significantly associated quantitative trait loci (QTLs) and 71 candidate genes.
In parallel, a gene co-expression network based on transcriptome sequencing was
constructed. The module associated with cellulose biosynthesis was highlighted.
By integrating GWAS and gene co-expression network analysis, some promising
candidate genes, such as ESKIMO1 (ESK1, BnaC08g26920D), CELLULOSE SYNTHASE 6
(CESA6, BnaA09g06990D), and FRAGILE FIBER 8 (FRA8, BnaC04g39510D), were
prioritized for further research. These findings revealed the genetic basis
underlying stem lodging and provided worthwhile QTLs and genes information for
genetic improvement of stem lodging resistance in B. napus.
PMID- 29946334
TI - Overexpression of CsCaM3 Improves High Temperature Tolerance in Cucumber.
AB - High temperature (HT) stress affects the growth and production of cucumbers, but
genetic resources with high heat tolerance are very scarce in this crop.
Calmodulin (CaM) has been confirmed to be related to the regulation of HT stress
resistance in plants. CsCaM3, a CaM gene, was isolated from cucumber inbred line
"02-8." Its expression was characterized in the present study. CsCaM3 transcripts
differed among the organs and tissues of cucumber plants and could be induced by
HTs or abscisic acid, but not by salicylic acid. CsCaM3 transcripts exhibited
subcellular localization to the cytoplasm and nuclei of cells. Overexpression of
CsCaM3 in cucumber plants has the potential to improve their heat tolerance and
protect against oxidative damage and photosynthesis system damage by regulating
the expression of HT-responsive genes in plants, including chlorophyll catabolism
related genes under HT stress. Taken together, our results provide useful
insights into stress tolerance in cucumber.
PMID- 29946335
TI - Hydraulic Strategy of Cactus Root-Stem Junction for Effective Water Transport.
AB - Cactus roots function as a hydraulic safety valve by conducting available water
quickly and preventing water loss under drought condition. In particular, the
root-stem (R-S) junction is responsible for effective water transport by direct
coupling of the water absorptive thin roots and the moisture-filled bulky stem.
In this study, the morphological features of the R-S junction were observed by
using X-ray micro-imaging technique. Their structural and functional
characteristics were also elucidated according to a hydrodynamic viewpoint. With
regard to the axial water transport through xylem, the R-S junction prevents
water leakage by embolizing large-scale vessels with relatively high hydraulic
conductivity. In addition, the axial theoretical hydraulic conductivity of xylem
vessels from the roots to the stem drastically increases to facilitate water
absorption and prevent water loss. The cortex cell layer of a cactus is thinner
than that of other plant species. In the viewpoint of radial conductivity, this
property can be the hydraulic strategy of the cactus R-S junction to transport
water quickly from the root surface into the xylem. These results suggest that
the R-S junction functions as a hydraulic safety valve that can maximize water
uptake in axial and radial directions at limited rainfall. This junction can also
prevent the stem from leaking water under drought condition.
PMID- 29946336
TI - Protein Extraction Methods Shape Much of the Extracted Proteomes.
PMID- 29946337
TI - Quality of horse F(ab')2 antitoxins and anti-rabies immunoglobulins: protein
content and anticomplementary activity.
AB - Background: Among other applications, immunotherapy is used for the post-exposure
treatment and/or prophylaxis of important infectious diseases, such as botulism,
diphtheria, tetanus and rabies. The effectiveness of serum therapy is widely
proven, but improvements on the immunoglobulin purification process and on the
quality control are necessary to reduce the amount of protein aggregates. These
may trigger adverse reactions in patients by activating the complement system and
inducing the generation of anaphylatoxins. Herein, we used immunochemical methods
to predict the quality of horse F(ab')2 anti-botulinum AB, anti-diphtheric,
antitetanic and anti-rabies immunoglobulins, in terms of amount of proteins and
protein aggregates. Methods: Samples were submitted to protein quantification,
SDS-PAGE, Western blot analysis and molecular exclusion chromatography. The
anticomplementary activity was determined in vitro by detecting the production of
C5a/C5a desArg, the most potent anaphylatoxin. Data were analyzed by one-way
ANOVA followed by Tukey's post-test, and differences were considered
statistically significant when p < 0.05. Results: Horse F(ab')2 antitoxins and
anti-rabies immunoglobulin preparations presented different amounts of protein.
SDS-PAGE and Western blot analyses revealed the presence of protein aggregates,
non-immunoglobulin contaminants and, unexpectedly, IgG whole molecules in the
samples, indicating the non-complete digestion of immunoglobulins. The
chromatographic profiles of antitoxins and anti-rabies immunoglobulins allowed to
estimate the percentage of contaminants and aggregates in the samples. Although
protein aggregates were present, the samples were not able to induce the
generation of C5a/C5a desArg in vitro, indicating that they probably contain
acceptable levels of aggregates. Conclusions: Anti-botulinum AB (bivalent), anti
diphtheric, antitetanic and anti-rabies horse F(ab')2 immunoglobulins probably
contain acceptable levels of aggregates, although other improvements on the
preparations must be carried out. Protein profile analysis and in vitro
anticomplementary activity of F(ab')2 immunoglobulin preparations should be
included as quality control steps, to ensure acceptable levels of aggregates,
contaminants and whole IgG molecules on final products, reducing the chances of
adverse reactions in patients.
PMID- 29946338
TI - Measuring the lactate-to-creatine ratio via 1H NMR spectroscopy can be used to
noninvasively evaluate apoptosis in glioma cells after X-ray irradiation.
AB - Background: Radiotherapy is among the commonly applied treatment options for
glioma, which is one of the most common types of primary brain tumor. To evaluate
the effect of radiotherapy noninvasively, it is vital for oncologists to monitor
the effects of X-ray irradiation on glioma cells. Preliminary research had showed
that PKC-iota expression correlates with tumor cell apoptosis induced by X-ray
irradiation. It is also believed that the lactate-to-creatine (Lac/Cr) ratio can
be used as a biomarker to evaluate apoptosis in glioma cells after X-ray
irradiation. In this study, we evaluated the relationships between the Lac/Cr
ratio, apoptotic rate, and protein kinase C iota (PKC-iota) expression in glioma
cells. Methods: Cells of the glioma cell lines C6 and U251 were randomly divided
into 4 groups, with every group exposed to X-ray irradiation at 0, 1, 5, 10 and
15 Gy. Single cell gel electrophoresis (SCGE) was conducted to evaluate the DNA
damage. Flow cytometry was performed to measure the cell cycle blockage and
apoptotic rates. Western blot analysis was used to detect the phosphorylated PKC
iota (p-PKC-iota) level. 1H NMR spectroscopy was employed to determine the Lac/Cr
ratio. Results: The DNA damage increased in a radiation dose-dependent manner (p
< 0.05). With the increase in X-ray irradiation, the apoptotic rate also
increased (C6, p < 0.01; U251, p < 0.05), and the p-PKC-iota level decreased (C6,
p < 0.01; U251, p < 0.05). The p-PKC-iota level negatively correlated with
apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-iota
level. Conclusion: The Lac/Cr ratio decreases with an increase in X-ray
irradiation and thus can be used as a biomarker to reflect the effects of X-ray
irradiation in glioma cells.
PMID- 29946339
TI - MicroRNA-488 inhibits tongue squamous carcinoma cell invasion and EMT by directly
targeting ATF3.
AB - Background: It has been reported that the expression of activating transcription
factor 3 (ATF3) is closely associated with both microRNA (miRNA) processing and
the progress of many cancers. Our study aimed to explore the interaction between
ATF3 and miR-488 in tongue squamous cell carcinoma (TSCC). Methods: Quantitative
real-time PCR was performed to detect the levels of ATF3 and miR-488 in TSCC
tissues and cell lines. Cell invasion and epithelial-mesenchymal transition (EMT)
were assessed to determine the biological functions of miR-488 and ATF3 in TSCC
cells. The mRNA and protein levels of ATF3 were measured using quantitative RT
PCR and western blotting. Luciferase assays were performed to validate ATF3 as an
miR-488 target in TSCC cells. Results: We found that the level of miR-488
significantly decreased and the expression of ATF3 significantly increased in
TSCC tissues and cell lines. A low level of miR-488 was closely associated with
increased expression of ATF3 in TSCC tissues. Introducing miR-488 significantly
inhibited the invasion and EMT of TSCC cells, and knockdown of miR-488 promoted
both processes. The bioinformatics analysis predicted that ATF3 is a potential
target gene of miR-488. The luciferase reporter assay showed that miR-488 could
directly target ATF3. ATF3 silencing had similar effects to miR-488
overexpression on TSCC cells. Overexpression of ATF3 in TSCC cells partially
reversed the inhibitory effects of the miR-488 mimic. Conclusion: miR-488
inhibited cell invasion and EMT of TSCC cells by directly downregulating ATF3
expression.
PMID- 29946340
TI - Prevalence of food allergens sensitization and food allergies in a group of
allergic Honduran children.
AB - Background: Food allergy is a public health problem that has increased in the
last decade. Despite the increasing rates in children, quality data on the burden
of these diseases is lacking particularly in developing countries. Honduras has
no studies in pediatric patients. Objectives: The objective of this research was
to identify the most common sensitization patterns to food through epicutaneous
skin testing and food allergy rates in children and their correlation with common
allergic diseases in a group of patients from Hospital of Pediatrics Maria.
Methods: Cross-sectional retrospective, descriptive study in which records and
database of all allergic patients in the immunology outpatient clinic from
Hospital of Pediatrics Maria were reviewed between the periods of January 2015
through June 2016. Results: A total of 365 children were analyzed, the age of
participants were in the range from 1 to 18 years, with an average of 9.8 years.
Sensitization to food allergens were found in 23, and 58.3% were poly-sensitized.
The most common food allergens that patients were sensitized to: milk 9.0%, eggs
6.9%, peanut 4.9% and pork meat 4.4%. Food allergy was confirmed via oral food
challenged in 9.3% of the patients. The most frequent food allergies found were:
cow's milk allergy 6%, hen's egg allergy 5.2% and wheat allergy 1.9%.
Conclusions: Milk and egg were the most common a food allergens found in the
population studied. Most of the patients were found to be poly-sensitized. The
frequent food allergies confirmed via oral food challenge were cow's milk
allergy, hen's egg allergy and wheat allergy.
PMID- 29946341
TI - The effect of pre-laying maternal immunization on offspring growth and immunity
differs across experimentally altered postnatal rearing conditions in a wild
songbird.
AB - Background: Prenatal antibody transfer is an immune-mediated maternal effect by
which females can shape postnatal offspring resistance to pathogens and
parasites. Maternal antibodies passed on to offspring provide primary protection
to neonates against diverse pathogenic antigens, but they may also affect
offspring growth and influence the development of an offspring's own immune
response. The effects of maternal antibodies on offspring performance commonly
require that the disease environment experienced by a mother prior to breeding
matches the environment encountered by her offspring after hatching/birth.
However, other circumstances, like postnatal rearing conditions that affect
offspring food availability, may also determine the effects of maternal
antibodies on offspring growth and immunity. To date, knowledge about how
prenatal immune-mediated maternal effects interact with various postnatal rearing
conditions to affect offspring development and phenotype in wild bird population
remains elusive. Here we experimentally studied the interactive effects of pre
laying maternal immunization with a bacterial antigen (lipopolysaccharide) and
post-hatching rearing conditions, altered by brood size manipulation, on
offspring growth and humoral immunity of wild great tits (Parus major). Results:
We found that maternal immunization and brood size manipulation interactively
affected the growth and specific humoral immune response of avian offspring.
Among nestlings reared in enlarged broods, only those that originated from
immunized mothers grew better and were heavier at fledging stage compared to
those that originated from non-immunized mothers. In contrast, no such effects
were observed among nestlings reared in non-manipulated (control) broods.
Moreover, offspring of immunized females had a stronger humoral immune response
to lipopolysaccharide during postnatal development than offspring of non
immunized females, but only when the nestling was reared in control broods.
Conclusions: This study demonstrates that offspring development and their ability
to cope with pathogens after hatching are driven by mutual influences of pathogen
induced prenatal maternal effects and post-hatching rearing conditions. Our
findings suggest that immune-mediated maternal effects may have context-dependent
influences on offspring growth and immune function, related to the postnatal
environmental conditions experienced by the progeny.
PMID- 29946342
TI - GLUT1 and lactose synthetase are critical genes for lactose synthesis in
lactating sows.
AB - Background: Lactose synthesis rate is an important factor in milk production and
quality in mammals. Understanding the lactose synthesis mechanism is crucial for
the improvement of milk quantity and quality. However, research on the temporal
gene changes regarding lactose synthesis during the whole lactation is still
limited. The objective of this study was to determine gene expression profiles
related to lactose synthesis in sows during lactation, and further identify the
critical steps or key factors in the lactose synthesis pathway. Methods: To
determine the temporal change of factors related to lactose synthesis in sows,
milk from eight multiparous Yorkshire sows (parity 3 to 6) was collected at 0 h,
2 h, 6 h, 12 h, 24 h, day 2, 3, 4, 7, 14, and 21 after birth of the first piglet.
Lactose content, prolactin and progesterone concentration, and gene or protein
expression related to lactose synthesis were measured. Results: The lactose yield
increased gradually from D2 to D21 and reached a maximum at D14 (3-fold from D2)
during lactation (P < 0.05). A similar trend was observed in IGF-1 and insulin
concentrations in milk, both of which were greatest at D3 with a subsequent
decrease during middle to late lactation. Conversely, milk prolactin and
progesterone concentrations moderately decreased with the progression of
lactation. The mRNA or protein expressions related to glucose transportation
(GLUT1), glucose-galactose interconversion (HK1 and UGP2), UDP-galactose
transportation (SLC35A2), and lactose synthetase (LALBA and B4GALT1) in the
lactose synthesis pathway were significantly upregulated during early to middle
lactation and plateaued by late lactation (P < 0.05). Conclusions: These novel
findings suggest that the increased lactose synthesis in lactation was related to
the coordinated upregulation of genes or enzymes in the lactose synthesis
pathway, and glucose transportation (GLUT1) and lactose synthetase (LALBA and
B4GALT1) might be the critical steps in the lactose synthesis pathway of sows
during lactation.
PMID- 29946343
TI - Novel anti-obesity effects of beer hops compound xanthohumol: role of AMPK
signaling pathway.
AB - Background: Obesity alters adipose tissue metabolic and endocrine functioning,
leading to an increased adiposity and release of pro-inflammatory cytokines.
Various phytochemicals have been reported to contribute to the beiging of white
adipose tissue in order to ameliorate obesity by increasing thermogenesis. Here,
we show that the prenylated chalcone, xanthohumol (XN), induces beiging of white
adipocytes, stimulates lipolysis, and inhibits adipogenesis of murine 3T3-L1
adipocytes and primary human subcutaneous preadipocytes and these effects are
partly mediated by the activation of the AMP-activated protein kinase (AMPK)
signaling pathway. Methods: 3T3-L1 adipocytes and primary human subcutaneous
preadipocytes were differentiated using a standard protocol and were treated with
various concentrations of XN, dorsomorphin, an AMPK inhibitor, or AICAR, an AMPK
activator, to investigate the effects on adipogenesis, beiging and lipolysis.
Results: XN induced beiging of white adipocytes as witnessed by the increased
expression of beige markers CIDE-A and TBX-1. XN increased mitochondrial
biogenesis, as evidenced by increased mitochondrial content, enhanced expression
of PGC-1alpha, and the thermogenic protein UCP1. Following 24 h of treatment, XN
also increased oxygen consumption rate. XN stimulated lipolysis of mature 3T3-L1
and primary human subcutaneous adipocytes and inhibited adipogenesis of maturing
adipocytes. XN activated AMPK and in turn, XN-induced upregulation of UCP1, p
ACC, HSL, and ATGL was downregulated in the presence of dorsomorphin. Likewise,
an XN-induced decrease in adipogenesis was reversed in the presence of
dorsomorphin. Conclusions: Taken together, XN demonstrates anti-obesity effects
by not only inducing beiging but also decreasing adipogenesis and inducing
lipolysis. The anti-obesity effects of XN are partly mediated by AMPK signaling
pathway suggesting that XN may have potential therapeutic implications for
obesity.
PMID- 29946344
TI - High-throughput method for ear phenotyping and kernel weight estimation in maize
using ear digital imaging.
AB - Background: Grain yield, ear and kernel attributes can assist to understand the
performance of maize plant under different environmental conditions and can be
used in the variety development process to address farmer's preferences. These
parameters are however still laborious and expensive to measure. Results: A low
cost ear digital imaging method was developed that provides estimates of ear and
kernel attributes i.e., ear number and size, kernel number and size as well as
kernel weight from photos of ears harvested from field trial plots. The image
processing method uses a script that runs in a batch mode on ImageJ; an open
source software. Kernel weight was estimated using the total kernel number
derived from the number of kernels visible on the image and the average kernel
size. Data showed a good agreement in terms of accuracy and precision between
ground truth measurements and data generated through image processing. Broad
sense heritability of the estimated parameters was in the range or higher than
that for measured grain weight. Limitation of the method for kernel weight
estimation is discussed. Conclusion: The method developed in this work provides
an opportunity to significantly reduce the cost of selection in the breeding
process, especially for resource constrained crop improvement programs and can be
used to learn more about the genetic bases of grain yield determinants.
PMID- 29946345
TI - IMP/GTP balance modulates cytoophidium assembly and IMPDH activity.
AB - Background: Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme
in de novo GTP biosynthesis, plays an important role in cell metabolism and
proliferation. It has been demonstrated that IMPDH can aggregate into a
macrostructure, termed the cytoophidium, in mammalian cells under a variety of
conditions. However, the regulation and function of the cytoophidium are still
elusive. Results: In this study, we report that spontaneous filamentation of
IMPDH is correlated with rapid cell proliferation. Intracellular IMP accumulation
promoted cytoophidium assembly, whereas elevated GTP level triggered
disassociation of aggregates. By using IMPDH2 CBS domain mutant cell models,
which are unable to form the cytoophidium, we have determined that the
cytoophidium is of the utmost importance for maintaining the GTP pool and normal
cell proliferation in the condition that higher IMPDH activity is required.
Conclusions: Together, our results suggest a novel mechanism whereby cytoophidium
assembly upregulates IMPDH activity and mediates guanine nucleotide homeostasis.
PMID- 29946346
TI - Clinical prediction score for superficial surgical site infection after
appendectomy in adults with complicated appendicitis.
AB - Background: Superficial surgical site infection (SSI) is common after
appendectomy. This study aims to determine a clinical prediction score for SSI
after appendectomy in complicated appendicitis. Methods: Data from randomized
controlled trial of delayed versus primary wound closures in complicated
appendicitis was used. Nineteen patient- and operative-related predictors were
selected in the logit model. Clinical prediction score was then constructed using
coefficients of significant predictors. Risk stratification was done by receiver
operating characteristic (ROC) curve analysis. Bootstrap technique was used to
internal validate the score. Results: Among 607 patients, the SSI incidence was
8.7% (95% CI 6.4, 11.2). Four predictors were significantly associated with SSI,
i.e., presence of diabetes, incisional length > 7 cm, fecal contamination, and
operative time > 75 min with the odds ratio of 2.6 (95% CI 1.2, 5.9), 2.8 (1.5,
5.4), 3.6 (1.9, 6.8), and 3.4 (1.8, 6.5), respectively. Clinical prediction score
ranged from 0 to 4.5 with its discrimination concordance (C) statistic of 0.74
(95% CI 0.66, 0.81). Risk stratification classified patients into very low, low,
moderate, and high risk groups for SSI when none, one, two, and more than two
risk factors were presented with positive likelihood ratio of 1.00, 1.45, 3.32,
and 9.28, respectively. A bootstrap demonstrated well calibration and thus good
internal validation. Conclusions: Diabetes, incisional length, fecal
contamination, and operative time could be used to predict SSI with acceptable
discrimination. This clinical risk prediction should be useful in prediction of
SSI. However, external validation should be performed. Trial registration:
ClinicalTrials.gov (ID NCT01659983), registered August 8, 2012.
PMID- 29946348
TI - Cost-consequence analysis of salvianolate injection for the treatment of coronary
heart disease.
AB - Background: Complicated with the impact of aging population and urbanization,
coronary heart disease (CHD) incurs more and more disease burdens in China.
Salvianolate injection is a Chinese patent drug widely used for treating CHD in
China. A series of studies have verified the efficacy of salvianolate injection ,
but the high drug cost has raised concerns. It is, therefore, important to
conduct cost-consequence analysis to demonstrate whether salvianolate injection
is associated with outcome improvement and cost containment. The aim of this
study was to retrospectively evaluate the cost-consequence of salvianolate
injection for the treatment of coronary heart disease by combining salvianolate
injection with conventional treatment from a societal perspective. Methods: We
retrospectively studied hospitalized patients with CHD from August 2011 to
December 2015 by using electronic medical record database. Patients who received
salvianolate injection combined with conventional treatment were selected as
exposed group, while those who received conventional treatment alone were
selected as unexposed group. Propensity score matching (PSM) analysis was used to
balance the characteristics of patients. After PSM, we evaluated hospital stay,
total nitrates dosage, total medical costs, and subcategories costs. Patients
with chronic ischemic heart disease were analyzed as a highly selected subcohort.
Results: For the overall group, hospital stay was significantly decreased by 2.9
days (P < 0.05) and total nitrates dosage was significantly decreased by 172.4 mg
(P < 0.05) in exposed group; cost savings of pharmacy cost, examination cost,
laboratory cost, operation cost and treatment was observed as significant (at P <
0.05); and the additional expenditure of Chinese patent drug (1174.9 CNY) was
less than the saving of total medical costs (2636.4 CNY). For chronic ischemic
heart disease subcohort, compared with unexposed group, significant decreases
were also found in hospital stay and total nitrates dosage (P < 0.05); cost
savings were significant (P < 0.05) for exposed group in terms of total medical
costs (4339.5 CNY) and subcategories costs (including pharmacy cost, examination
cost, operation cost and treatment cost); and the additional expenditure of
Chinese patent drug (1189.3 CNY) was less than the saving of total medical costs.
Conclusion: Compared with conventional treatment for the treatment of CHD,
combination of salvianolate injection and conventional treatment was associated
with a reduction in hospital stay and total nitrates dosage. The acquisition cost
of Chinese patent drug (including salvianolate injection) was offset by a higher
reduction in total medical costs, especially for chronic ischemic heart disease.
PMID- 29946349
TI - Isorhynchophylline alleviates learning and memory impairments induced by aluminum
chloride in mice.
AB - Background: To evaluate the effect of Isorhynchophylline (IRN) on the learning
and memory impairments induced by aluminum chloride (AlCl3) in mice. Methods:
Fifty male Balb-c mice (4-month-old) were randomly divided into five groups:
control, AlCl3 plus vehicle, AlCl3 plus IRN (20 mg/kg), AlCl3 plus IRN (40 mg/kg)
and AlCl3 plus donepezil (5 mg/kg). Learning and memory impairments were induced
in mice by subcutaneously injecting with AlCl3 (50 mg/kg) once a day for 8
consecutive weeks. At the same time, mice were intragastrically given vehicle or
IRN (20 and 40 mg/kg) or donepezil (5 mg/kg) 30 min before each AlCl3 injection.
The spatial learning and memory function was assessed using radial arm maze.
After sacrificed, the parameters of oxidative stress and cholinergic system in
the brain tissues were examined with ELISA kits. Moreover, the expression of
nuclear factor kappa B (NF-kappaB) signaling pathway was analyzed with western
blotting. Results: The results showed that treatment with IRN could significantly
ameliorate the cognitive deficits induced by AlCl3 in mice. In addition,
treatment with IRN was found to reduce the level of malondialdehyde, enhance the
activities of superoxide dismutases and catalase, increase the level of
glutathione, and markedly inhibit the activity of acetylcholinesterase (AChE) in
the brain tissues of the AlCl3-treated mice. Moreover, IRN significantly
suppressed the phosphorylation of NF-kappaB p65 and IkappaBalpha in the brain
tissues of AlCl3-treated mice. However, IRN did not show significant effect on
the activity of butyrylcholinesterase. Conclusion: Our findings demonstrated for
the first time that IRN could alleviate learning and memory impairments induced
by AlCl3 in mice. The neuroprotective effect of IRN against AlCl3-induced AD is
probably mediated, at least in part, through inhibiting the AChE activity and
reducing the oxidative damage of brain tissue via suppress the NF-kappaB
signaling pathway. These results contributed to a better understanding of the in
vivo anti-AD mechanism of IRN. It was concluded that IRN could protect the
learning and memory function.
PMID- 29946350
TI - Effective authentication of Placenta Hominis.
AB - Background: Human placenta is used to make the medicinal product Placenta Hominis
in Asian countries. With its therapeutic benefits and limited supply, intentional
or inadvertent adulteration is found in the market. In order to enforce the
implementation of product description laws and protect customer rights, we
established a hierarchical protocol involving morphological, chemical,
biochemical and molecular diagnosis to authenticate this medicinal product.
Methods: Ten samples claimed as Placenta Hominis were collected from herbal shops
in China, Hong Kong and Taiwan. Species-specific diagnostic primers for human,
cow, deer and sheep were designed for PCR amplification and subsequent DNA
sequencing for species identification. Commercially available pregnancy test
strip was used to detect human chorionic gonadotropin (hCG), and progesterone
competitive ELISA kit was used to detect the presence of progesterone in samples.
The presence of starch in samples was tested by adding small amount of iodine
solution onto the samples. Results: Among the ten samples studied, results showed
that no cow, deer and sheep DNA sequence was found in all samples. Five samples
were genuine with the presence of human DNA, hCG and progesterone accompanied
with the absence of starch fillers. On the other hand, four samples were
adulterants which may be made from starch products. In addition, a sample was
found as a mixture of Placenta Hominis and starch fillers, and it did not conform
to the product requirement of Placenta Hominis. Conclusions: The comprehensive
protocol developed involving morphological, chemical, biochemical and molecular
diagnosis provides an accurate method to regulatory bodies and testing
laboratories for the quality control of Placenta Hominis.
PMID- 29946347
TI - Bologna guidelines for diagnosis and management of adhesive small bowel
obstruction (ASBO): 2017 update of the evidence-based guidelines from the world
society of emergency surgery ASBO working group.
AB - Background: Adhesive small bowel obstruction (ASBO) is a common surgical
emergency, causing high morbidity and even some mortality. The adhesions causing
such bowel obstructions are typically the footprints of previous abdominal
surgical procedures. The present paper presents a revised version of the Bologna
guidelines to evidence-based diagnosis and treatment of ASBO. The working group
has added paragraphs on prevention of ASBO and special patient groups. Methods:
The guideline was written under the auspices of the World Society of Emergency
Surgery by the ASBO working group. A systematic literature search was performed
prior to the update of the guidelines to identify relevant new papers on
epidemiology, diagnosis, and treatment of ASBO. Literature was critically
appraised according to an evidence-based guideline development method. Final
recommendations were approved by the workgroup, taking into account the level of
evidence of the conclusion. Recommendations: Adhesion formation might be reduced
by minimally invasive surgical techniques and the use of adhesion barriers. Non
operative treatment is effective in most patients with ASBO. Contraindications
for non-operative treatment include peritonitis, strangulation, and ischemia.
When the adhesive etiology of obstruction is unsure, or when contraindications
for non-operative management might be present, CT is the diagnostic technique of
choice. The principles of non-operative treatment are nil per os, naso-gastric,
or long-tube decompression, and intravenous supplementation with fluids and
electrolytes. When operative treatment is required, a laparoscopic approach may
be beneficial for selected cases of simple ASBO.Younger patients have a higher
lifetime risk for recurrent ASBO and might therefore benefit from application of
adhesion barriers as both primary and secondary prevention. Discussion: This
guideline presents recommendations that can be used by surgeons who treat
patients with ASBO. Scientific evidence for some aspects of ASBO management is
scarce, in particular aspects relating to special patient groups. Results of a
randomized trial of laparoscopic versus open surgery for ASBO are awaited.
PMID- 29946351
TI - In silico approach in reveal traditional medicine plants pharmacological material
basis.
AB - In recent years, studies of traditional medicinal plants have gradually increased
worldwide because the natural sources and variety of such plants allow them to
complement modern pharmacological approaches. As computer technology has
developed, in silico approaches such as virtual screening and network analysis
have been widely utilized in efforts to elucidate the pharmacological basis of
the functions of traditional medicinal plants. In the process of new drug
discovery, the application of virtual screening and network pharmacology can
enrich active compounds among the candidates and adequately indicate the
mechanism of action of medicinal plants, reducing the cost and increasing the
efficiency of the whole procedure. In this review, we first provide a detailed
research routine for examining traditional medicinal plants by in silico
techniques and elaborate on their theoretical principles. We also survey common
databases, software programs and website tools that can be used for virtual
screening and pharmacological network construction. Furthermore, we conclude with
a simple example that illustrates the whole methodology, and we present
perspectives on the development and application of this in silico methodology to
reveal the pharmacological basis of the effects of traditional medicinal plants.
PMID- 29946352
TI - Does chronic disease influence susceptibility to the effects of air pollution on
depressive symptoms in China?
AB - Background: Exogenous stressors resulting from air pollution can lead to
depression and chronic disease. Chinese levels of air pollution are among the
highest in the world, and although associated adverse health effects are
gradually emerging, research determining individual vulnerability is limited.
This study estimated the association between air pollution and depressive
symptoms and identified whether chronic disease influences an individual's
susceptibility to depressive symptoms relating to air pollution. Methods:
Individual sample data from the China Health and Retirement Longitudinal Study
and a group of city-level variables in 2011 and 2013 were used with the random
effects model and Tobit model. Adjustments were made for demographic,
socioeconomic status, health behavior, and city-level climate variables with
respect to living areas. Analysis was also stratified using chronic disease
characteristics. Results: The total Center for Epidemiological Studies Depression
scale evaluating depressive symptoms ranged between 7 and 28 [average 11.623 (SD
= 4.664)]. An 1% increase in sulfur dioxide and total suspended particulate
emission intensities was associated with depressive symptoms scores that were
1.266 (SE = 0.107, P < 0.001, 95% CI 1.057-1.475) and 1.318 (SE = 0.082, P <
0.001, 95% CI 1.157-1.480) higher, respectively. Compared to respondents without
chronic disease, those with chronic diseases such as hypertension, dyslipidemia,
diabetes or high blood sugar, cardiovascular diseases, cancer or malignant tumor,
liver disease, chronic lung diseases, kidney disease, stomach or other digestive
disease, arthritis or rheumatism, and asthma had scores that were higher for
depressive symptoms. Conclusions: Results confirm that the adverse health effects
of air pollution should be considered when developing air pollution policies.
Findings also provide justification for mental health interventions targeting air
pollution exposure, especially for people with chronic diseases.
PMID- 29946353
TI - Validation of the Child Post-Traumatic Cognitions Inventory in Korean survivors
of sexual violence.
AB - Background: Dysfunctional cognitions related to trauma is an important factor in
the development and maintenance of post-traumatic stress disorder symptoms in
children and adolescents. The Child Post-traumatic Cognitions Inventory (CPTCI)
assesses such cognitions about trauma. We investigated the psychometric
properties of the Korean version of CPTCI and its short form by surveying child
and adolescent survivors of sexual violence. Methods: Children and adolescents
aged 7-16 years (N = 237, Mage = 12.6, SD = 2.3, 222 [93.7%] were female) who
were exposed to sexual violence were included in this survey. We assessed the
factor structure, internal consistency, and validity of the CPTCI and its short
form through data analysis. Results: Confirmatory factor analysis results
supported the two-factor model presented in the original study. The total scale,
its subscales, and the short form had good internal consistency (Cronbach's alpha
= .96 for total scale and .91-.95 for the other scales). The CPTCI showed high
correlations with scales measuring post-traumatic stress symptoms (r = .77-.80),
anxiety (r = .69-.71), and depression (r = .74-.77); the correlation with post
traumatic stress symptoms was the highest. The differences in CPTCI scores per
post-traumatic stress symptom levels were significant (all p < .001) Sex
differences in CPTCI scores were not significant (p > .05 for all comparisons);
however, the scores exhibited differences per age group (all p < .001).
Conclusions: The results indicate that the Korean version of the CPTCI is a valid
and reliable scale; therefore, it may be a valuable tool for assessing
maladaptive cognitions related to trauma in research and clinical settings.
PMID- 29946354
TI - Effectiveness of a cognitive behavioural therapy-based anxiety prevention
programme at an elementary school in Japan: a quasi-experimental study.
AB - Background: The efficacy of cognitive behavioural therapy (CBT) for anxiety
related problems in children is empirically supported. In addition, universal
anxiety prevention programmes based on CBT have been demonstrated in recent
years. The purpose of this study was to verify the effectiveness of a CBT based
original programme 'Journey of the Brave,' aiming to prevent anxiety disorders
and anxiety-related problems for Japanese children aged 10-12 years old. Methods:
Intervention groups from two classes of 5th grade elementary students (n = 41)
received ten 45-min programme sessions. The control group was drawn from one
class of 5th grade children (n = 31) from a nearby school. All participants
completed the Spence Children's Anxiety Scale (SCAS) at pre, post, and 3 months
follow-up. Mixed-effects model for repeated measures analysis was conducted.
Results: The mean anxiety score on the SCAS for the intervention group was
significantly reduced at both post intervention and 3 months follow-up compared
with the control group. The group differences on the SCAS from baseline to post
test were - 5.321 (95% CI - 10.12 to - 0.523, p = 0.030), and at the 3-month
follow-up were - 7.104 (95% CI - 11.90 to - 2.306, p = 0.004). Conclusions: The
effectiveness of the anxiety prevention programme 'Journey of the Brave' was
verified though this study using a quasi-experimental design on a small
sample.Trial registration: UMIN000009021.
PMID- 29946355
TI - Production of butyric acid from acid hydrolysate of corn husk in fermentation by
Clostridium tyrobutyricum: kinetics and process economic analysis.
AB - Background: Butyric acid is an important chemical currently produced from
petrochemical feedstocks. Its production from renewable, low-cost biomass in
fermentation has attracted large attention in recent years. In this study, the
feasibility of corn husk, an abundant agricultural residue, for butyric acid
production by using Clostridium tyrobutyricum immobilized in a fibrous bed
bioreactor (FBB) was evaluated. Results: Hydrolysis of corn husk (10% solid
loading) with 0.4 M H2SO4 at 110 degrees C for 6 h resulted in a hydrolysate
containing ~ 50 g/L total reducing sugars (glucose:xylose = 1.3:1.0). The
hydrolysate was used for butyric acid fermentation by C. tyrobutyricum in a FBB,
which gave 42.6 and 53.0% higher butyric acid production from glucose and xylose,
respectively, compared to free-cell fermentations. Fermentation with glucose and
xylose mixture (1:1) produced 50.37 +/- 0.04 g L-1 butyric acid with a yield of
0.38 +/- 0.02 g g-1 and productivity of 0.34 +/- 0.03 g L-1 h-1. Batch
fermentation with corn husk hydrolysate produced 21.80 g L-1 butyric acid with a
yield of 0.39 g g-1, comparable to those from glucose. Repeated-batch
fermentations consistently produced 20.75 +/- 0.65 g L-1 butyric acid with an
average yield of 0.39 +/- 0.02 g g-1 in three consecutive batches. An extractive
fermentation process can be used to produce, separate, and concentrate butyric
acid to > 30% (w/v) sodium butyrate at an economically attractive cost for
application as an animal feed supplement. Conclusion: A high concentration of
total reducing sugars at ~ 50% (w/w) yield was obtained from corn husk after acid
hydrolysis. Stable butyric acid production from corn husk hydrolysate was
achieved in repeated-batch fermentation with C. tyrobutyricum immobilized in a
FBB, demonstrating that corn husk can be used as an economical substrate for
butyric acid production.
PMID- 29946356
TI - Redox processes acidify and decarboxylate steam-pretreated lignocellulosic
biomass and are modulated by LPMO and catalase.
AB - Background: The bioconversion of lignocellulosic feedstocks to ethanol is being
commercialised, but further process development is required to improve their
economic feasibility. Efficient saccharification of lignocellulose to fermentable
sugars requires oxidative cleavage of glycosidic linkages by lytic polysaccharide
monooxygenases (LPMOs). However, a proper understanding of the catalytic
mechanism of this enzyme class and the interaction with other redox processes
associated with the saccharification of lignocellulose is still lacking. The in
use stability of LPMO-containing enzyme cocktails is increased by the addition of
catalase implying that hydrogen peroxide (H2O2) is generated in the slurry during
incubation. Therefore, we sought to characterize the effects of enzymatic and
abiotic sources of H2O2 on lignocellulose hydrolysis to identify parameters that
could improve this process. Moreover, we studied the abiotic redox reactions of
steam-pretreated wheat straw as a function of temperature and dry-matter (DM)
content. Results: Abiotic reactions in pretreated wheat straw consume oxygen,
release carbon dioxide (CO2) to the slurry, and decrease the pH. The magnitude of
these reactions increased with temperature and with DM content. The presence of
LPMO during saccharification reduced the amount of CO2 liberated, while the
effect on pH was insignificant. Catalase led to increased decarboxylation through
an unknown mechanism. Both in situ-generated and added H2O2 caused a decrease in
pH. Conclusions: Abiotic redox processes similar to those that occur in natural
water-logged environments also affect the saccharification of pretreated
lignocellulose. Heating of the lignocellulosic material and adjustment of pH
trigger rapid oxygen consumption and acidification of the slurry. In industrial
settings, it will be of utmost importance to control these processes. LPMOs
interact with the surrounding redox compounds and redirect abiotic electron flow
from decarboxylating reactions to fuel the oxidative cleavage of glycosidic bonds
in cellulose.
PMID- 29946358
TI - The DeltaF/Fm'-guided supply of nitrogen in culture medium facilitates
sustainable production of TAG in Nannochloropsis oceanica IMET1.
AB - Background: Triacylglycerol (TAG) from photosynthetic microalgae is a sustainable
feedstock for biodiesel production. Physiological stress triggers microalgal TAG
accumulation. However excessive physiological stress will impair the
photosynthesis system seriously thus decreasing TAG productivity because of the
low biomass production. Hence, it is critical to quantitatively and timely
monitor the degree of the stress while the microalgal cells growing so that the
optimal TAG productivity can be obtained. Results: The lack of an on-line
monitored indicator has limited our ability to gain knowledge of cellular "health
status" information regarding high TAG productivity. Therefore, to monitor the
degree of nitrogen stress of the cells, we investigated the correlation between
the photosynthetic system II (PS II) quantum yield and the degree of stress based
on the high relevancy between photosynthetic reduction and nitrogen stress
induced TAG accumulation in microalgal cells. DeltaF/Fm', which is the
chlorophyll fluorescence parameter that reflects the effective capability of PS
II, was identified to be a critical factor to indicate the degree of stress of
the cells. In addition, the concept of a nitrogen stress index has been defined
to quantify the degree of stress. Based on this index and by monitoring
DeltaF/Fm' and guiding the supply of nitrogen in culture medium to maintain a
stable degree of stress, a stable and efficient semi-continuous process for TAG
production has been established. Conclusion: The results indicate that the semi
continuous cultivation process with a controlled degree of stress by monitoring
the DeltaF/Fm' indicator will have a significant impact on microalgal TAG
production, especially for the outdoor controllable cultivation of microalgae on
a large scale.
PMID- 29946357
TI - Defining functional diversity for lignocellulose degradation in a microbial
community using multi-omics studies.
AB - Background: Lignocellulose is one of the most abundant forms of fixed carbon in
the biosphere. Current industrial approaches to the degradation of lignocellulose
employ enzyme mixtures, usually from a single fungal species, which are only
effective in hydrolyzing polysaccharides following biomass pre-treatments. While
the enzymatic mechanisms of lignocellulose degradation have been characterized in
detail in individual microbial species, the microbial communities that
efficiently breakdown plant materials in nature are species rich and secrete a
myriad of enzymes to perform "community-level" metabolism of lignocellulose.
Single-species approaches are, therefore, likely to miss important aspects of
lignocellulose degradation that will be central to optimizing commercial
processes. Results: Here, we investigated the microbial degradation of wheat
straw in liquid cultures that had been inoculated with wheat straw compost.
Samples taken at selected time points were subjected to multi-omics analysis with
the aim of identifying new microbial mechanisms for lignocellulose degradation
that could be applied in industrial pre-treatment of feedstocks. Phylogenetic
composition of the community, based on sequenced bacterial and eukaryotic
ribosomal genes, showed a gradual decrease in complexity and diversity over time
due to microbial enrichment. Taxonomic affiliation of bacterial species showed
dominance of Bacteroidetes and Proteobacteria and high relative abundance of
genera Asticcacaulis, Leadbetterella and Truepera. The eukaryotic members of the
community were enriched in peritrich ciliates from genus Telotrochidium that
thrived in the liquid cultures compared to fungal species that were present in
low abundance. A targeted metasecretome approach combined with
metatranscriptomics analysis, identified 1127 proteins and showed the presence of
numerous carbohydrate-active enzymes extracted from the biomass-bound fractions
and from the culture supernatant. This revealed a wide array of hydrolytic
cellulases, hemicellulases and carbohydrate-binding modules involved in
lignocellulose degradation. The expression of these activities correlated to the
changes in the biomass composition observed by FTIR and ssNMR measurements.
Conclusions: A combination of mass spectrometry-based proteomics coupled with
metatranscriptomics has enabled the identification of a large number of
lignocellulose degrading enzymes that can now be further explored for the
development of improved enzyme cocktails for the treatment of plant-based
feedstocks. In addition to the expected carbohydrate-active enzymes, our studies
reveal a large number of unknown proteins, some of which may play a crucial role
in community-based lignocellulose degradation.
PMID- 29946359
TI - Heterotrophic cultivation of Auxenochlorella protothecoides using forest biomass
as a feedstock for sustainable biodiesel production.
AB - Background: The aim of this work was to establish a process for the heterotrophic
growth of green microalgae using forest biomass hydrolysates. To provide a carbon
source for the growth of the green microalgae, two forest biomasses (Norway
spruce and silver birch) were pretreated with a hybrid organosolv-steam explosion
method, resulting in inhibitor-free pretreated solids with a high cellulose
content of 77.9% w/w (birch) and 72% w/w (spruce). Pretreated solids were
hydrolyzed using commercial cellulolytic enzymes to produce hydrolysate for the
culture of algae. Results: The heterotrophic growth of A. protothecoides was
assessed using synthetic medium with glucose as carbon source, where the effect
of sugar concentration and the carbon-to-nitrogen ratio were optimized, resulting
in accumulation of lipids at 5.42 +/- 0.32 g/L (64.52 +/- 0.53% lipid content)
after 5 days of culture on glucose at 20 g/L. The use of birch and spruce
hydrolysates was favorable for the growth and lipid accumulation of the algae,
resulting in lipid production of 5.65 +/- 0.21 g/L (66 +/- 0.33% lipid content)
and 5.28 +/- 0.17 g/L (63.08 +/- 0.71% lipid content) when grown on birch and
spruce, respectively, after only 120 h of cultivation. Conclusions: To the best
of our knowledge, this is the first report of using organosolv pretreated wood
biomass hydrolysates for the growth and lipid production of microalgae in the
literature. The pretreatment process used in this study provided high
saccharification of biomass without the presence of inhibitors. Moreover, the
lipid profile of this microalga showed similar contents to vegetable oils which
improve the biodiesel properties.
PMID- 29946360
TI - The grass is not always greener: a multi-institutional pilot study of marijuana
use and acute pain management following traumatic injury.
AB - Background: Widespread legislative efforts to legalize marijuana have increased
the prevalence of marijuana use and abuse. The effects of marijuana on pain
tolerance and analgesic pain management in the acute pain setting have not been
reported. Although marijuana has been shown to have antinociceptive effects and
is approved for medical use to treat chronic pain, anecdotal evidence suggests
marijuana users admitted with traumatic injuries experience poorer pain control
than patients who do not use marijuana. We hypothesized that marijuana users
would report higher pain scores and require more opioid analgesia following
traumatic injury. Methods: This retrospective pilot study included all patients
involved in motor vehicle crashes, consecutively admitted to four trauma centers
from 1/1/2016-4/30/2016. Marijuana status was examined as non-use and use, and
was further categorized as chronic and episodic use. We performed a repeated
measures mixed model to examine the association between marijuana use and a)
average daily opioid consumption and b) average daily pain scores (scale 0-10).
Opioid analgesics were converted to be equianalgesic to 1 mg IV hydromorphone.
Results: Marijuana use was reported in 21% (54/261), of which 30% reported
chronic use (16/54). Marijuana use was reported more frequently in Colorado
hospitals (23-29%) compared to the hospital in Texas (6%). Drug use with other
prescription/street drugs was reported in 9% of patients. Other drug use was a
significant effect modifier and results were presented after stratification by
drug use. After adjustment, marijuana users who did not use other drugs consumed
significantly more opioids (7.6 mg vs. 5.6 mg, p < 0.001) and reported higher
pain scores (4.9 vs. 4.2, p < 0.001) than non-marijuana users. Conversely, in
patients who used other drugs, there were no differences in opioid consumption
(5.6 mg vs. 6.1 mg, p = 0.70) or pain scores (5.3 vs. 6.0, p = 0.07) with
marijuana use compared to non-use, after adjustment. Chronic marijuana use was
associated with significantly higher opioid consumption compared to episodic
marijuana use in concomitant drug users (11.3 mg vs. 4.4 mg, p = 0.008) but was
similar in non-drug users (p = 0.41). Conclusion: These preliminary data suggest
that marijuana use, especially chronic use, may affect pain response to injury by
requiring greater use of opioid analgesia. These results were less pronounced in
patients who used other drugs.
PMID- 29946361
TI - A foetus with 18p11.32-q21.2 duplication and Xp22.33-p11.1 deletion derived from
a maternal reciprocal translocation t(X;18)(q13;q21.3).
AB - Background: Non-invasive prenatal testing (NIPT) evaluates circulating cell-free
DNA (cfDNA) and has been widely applied, with highly accurate results for
detecting foetal trisomies 21, 18 and 13. Recently, increasing attention has been
paid to the clinical application of the non-invasive detection of foetal sub
chromosomal duplications and deletions beyond common aneuploidies. Case
presentation: A 32-year-old healthy pregnant woman was referred to the Medical
Genetic Centre of Ganzhou Maternal and Child Health Care Hospital. As routine
practice, ultrasound examination at a gestational age of 16 weeks showed that the
foetus is normal. To avoid invasive prenatal diagnosis procedures, an NIPT was
offered to further screen for common foetal chromosomal abnormalities. The result
showed that there was an approximately 50.94 Mb duplication in p11.32-q21.2 of
chromosome 18 and an approximately 58.46 Mb deletion in p22.33-p11.1 of
chromosome X. In addition, the chromosome karyotypes of the parents and foetus
were also analysed. Chromosome karyotype analysis results showed that foetal
karyotype was 46,X,der(18), the maternal karyotype was 46,XX,t(X;18)(q13;q21.3),
and the paternal karyotype revealed no obvious abnormality. Conclusion: In this
case, we successfully detected a healthy pregnant woman with balanced
translocation X;18(q13;q21.3) and described the foetal karyotype as
46,X,der(18)t(X;18)(q11;q21.1)mat. Our report illustrated these cases which
present complex X;autosome balance translocation and X;autosome unbalance
translocation which may contribute to severe clinical phenotypes. In addition,
our report also proved that the interruption of genes in the Xq critical region
is not only reason of primary infertility. Finally, we prompted that NIPT might
play a role in the first trimester screening of sub-chromosomal rearrangement.
PMID- 29946362
TI - Erratum: Publisher Correction: Is DNA methylation the new guardian of the genome?
AB - [This corrects the article DOI: 10.1186/s13039-017-0314-8.].
PMID- 29946363
TI - Delayed Coronary Obstruction After Transcatheter Aortic Valve Implantation is not
the Structural Equivalent of Late Stent Thrombosis After Percutaneous Coronary
Intervention.
PMID- 29946364
TI - Sarcopenia increases the risk for mortality in patients who undergo amputation
for diabetic foot.
AB - Background: Although there have been reports that diabetes affects the prevalence
of sarcopenia, no studies have examined the relationship between sarcopenia and
mortality in patients undergoing leg amputation. The purpose of this study is to
determine whether sarcopenia affects the mortality rate of patients undergoing
diabetic foot amputation. Methods: From among patients who underwent limb
amputation for diabetes complications, this study included 167 patients who
underwent abdominal CT within 1 year of amputation. We defined sarcopenia using
sex-specific cut-off points for the L3 skeletal muscle index. The 5-year survival
rate was analyzed. All patients were divided into two groups and compared
according to the presence of sarcopenia. The mortality rate according to
sarcopenia was assessed via the Kaplan-Meier method and log-rank test. Uni- and
multivariate Cox regression analyses evaluated factors associated with survival
rate. Results: Among the total of 167 patients, the overall 5-year mortality rate
was 52.7%. Of the 112 patients with sarcopenia, the 5-year mortality rate was
60.7%. Of the 55 patients without sarcopenia, the 5-year mortality rate was
36.4%. Kaplan-Meier analysis showed a high mortality of the sarcopenia group in
the univariate (p = 0.016) and multivariate (p = 0.047) analysis. Conclusions:
Our study is the first to analyze the relationship between diabetic amputation
and sarcopenia. Sarcopenia increases the risk of mortality in patients who
undergo amputation for diabetic foot. Therefore, patients with diabetes should be
careful to prevent sarcopenia with enough regular exercise as well as prevent
diabetic foot disease.
PMID- 29946365
TI - High carriage of adherent invasive E. coli in wildlife and healthy individuals.
AB - Background: Adherent invasive Escherichia coli (AIEC) are suspected to be
involved in the pathogenesis of inflammatory bowel diseases. Since AIEC was first
described in 1999, despite important progress on its genomic and immune
characterizations, some crucial questions remain unanswered, such as whether
there exists a natural reservoir, or whether there is asymptomatic carriage. The
ECOR collection, including E. coli strains isolated mainly from the gut of
healthy humans and animals, constitutes an ideal tool to investigate AIEC
prevalence in healthy condition. A total of 61 E. coli strains were examined for
characteristics of AIEC. Methods: The adhesion, invasion and intramacrophage
replication capabilities (AIEC phenotype) of 61 intestinal E. coli strains were
determined. The absence of virulence-associated diarrheagenic E. coli pathotypes
(EPEC, ETEC, EIEC, EHEC, DAEC, EAEC), and uropathogenic E. coli was checked.
Results: Out of 61 intestinal strains, 13 (21%) exhibit the AIEC phenotype, 7 are
from human origin and 6 are from animal origin. Prevalence of AIEC strains is
about 24 and 19% in healthy humans and animals respectively. These strains are
highly genetically diverse as they are distributed among the main described
phylogroups. Among E. coli strains from the ECOR collection, we also detected
strains able to detach I-407 cells. Conclusions: Our study described for the
first time AIEC strains isolated from the feces of healthy humans and animals.
PMID- 29946367
TI - Associations of serum calcium levels and dietary calcium intake with incident
type 2 diabetes over 10 years: the Korean Genome and Epidemiology Study (KoGES).
AB - Background: Previous evidence regarding the associations between serum calcium
concentrations, dietary calcium intake, and type 2 diabetes (T2D) is limited. We
investigated the longitudinal associations of serum calcium levels and dietary
calcium intake with T2D development. Methods: This study used data from the
Ansung-Ansan cohort, a community-based, prospective cohort that was followed up
for 10 years. Cox regression models adjusted for potential confounders were used
to evaluate the associations of serum calcium levels (mean, 9.41 mg/dL) and
dietary calcium intake (median, 389.59 mg/day) with T2D incidence. Association
between dietary calcium intake and serum calcium levels was assessed using linear
regression models. Results: Albumin-adjusted serum calcium levels were not
associated with T2D risk (hazard ratio [HR] = 1.07, 95% confidence interval [CI]
0.96, 1.19, p-value = 0.2333). A one-unit increase in log-transformed, energy
adjusted dietary calcium intake was associated with a decreased risk of T2D (HR =
0.88, 95% CI 0.77, 1.00, p-value = 0.0460) and lower albumin-adjusted serum
calcium levels (beta = - 0.04, 95% CI - 0.07, - 0.02, p-value = 0.0014). The
associations did not differ according to sex (all p-values for interaction >
0.10). Conclusions: Serum calcium levels were not associated with T2D risk, while
higher dietary calcium intake was associated with a decreased risk of T2D
development. These results have public health implications for predicting and
preventing T2D development, as well as providing guidelines for diet and calcium
supplementation.
PMID- 29946366
TI - Optimal cut-off points for waist circumference in the definition of metabolic
syndrome in Brazilian adults: baseline analyses of the Longitudinal Study of
Adult Health (ELSA-Brasil).
AB - Background: Waist circumference (WC) has been incorporated in the definition of
the metabolic syndrome (MetS) but the exact WC cut-off points across populations
are not clear. The Joint Interim Statement (JIS) suggested possible cut-offs to
different populations and ethnic groups. However, the adequacy of these cut-offs
to Brazilian adults has been scarcely investigated. The objective of the study is
to evaluate possible WC thresholds to be used in the definition of MetS using
data from the Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter
cohort study of civil servants (35-74 years old) of six Brazilian cities.
Methods: We analyzed baseline data from 14,893 participants (6772 men and 8121
women). A MetS was defined according to the JIS criteria, but excluding WC and
thus requiring 2 of the 4 remaining elements. We used restricted cubic spline
regression to graph the relationship between WC and MetS. We identified optimal
cut-off points which maximized joint sensitivity and specificity (Youden's index)
from Receiver Operator Characteristic Curves. We also estimated the C-statistics
using logistic regression. Results: We found no apparent threshold for WC in
restricted cubic spline plots. Optimal cut-off for men was 92 cm (2 cm lower than
that recommended by JIS for Caucasian/Europids or Sub-Saharan African men), but 2
cm higher than that recommended for ethnic Central and South American. For women,
optimal cut-off was 86, 6 cm higher than that recommended for Caucasian/Europids
and ethnic Central and South American. Optimal cut-offs did not very across age
groups and most common race/color categories (except for Asian men, 87 cm).
Conclusions: Sex-specific cut-offs for WC recommended by JIS differ from optimal
cut-offs we found for adult men and women of Brazil's most common ethnic groups.
PMID- 29946368
TI - The effects of probiotic supplementation on metabolic status in type 2 diabetic
patients with coronary heart disease.
AB - Background: This study was conducted to evaluate the effects of probiotic
supplementation on metabolic profiles in diabetic patients with coronary heart
disease (CHD). Methods: This randomized, double-blind, placebo-controlled trial
was performed among 60 diabetic patients with CHD, aged 40-85 years at a
cardiology clinic in Kashan, Iran, from October 2017 through January 2018.
Patients were randomly divided into two groups to take either probiotic
supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were
taken at the beginning of the study and after the 12-week intervention to
determine related markers. Results: After 12-week intervention, probiotic
supplementation significantly decreased fasting plasma glucose (beta - 20.02
mg/dL; 95% CI - 33.86, - 6.17; P = 0.005), insulin (beta - 2.09 uIU/mL; 95% CI -
3.77, - 0.41; P = 0.01), insulin resistance (beta - 0.50; 95% CI - 0.96, - 0.03;
P = 0.03) and total-/HDL-cholesterol ratio (beta - 0.27; 95% CI - 0.52, - 0.03; P
= 0.02), and significantly increased insulin sensitivity (beta 0.008; 95% CI
0.001, 0.01; P = 0.02) and HDL-cholesterol levels (beta 2.52 mg/dL; 95% CI 0.04,
5.00; P = 0.04) compared with the placebo. Moreover, probiotic supplementation
led to a significant reduction in serum high sensitivity C-reactive protein (beta
- 0.88 mg/L; 95% CI - 1.39, - 0.38; P = 0.001), and a significant elevation in
total antioxidant capacity (beta 108.44 mmol/L; 95% CI 47.61, 169.27; P = 0.001)
and total glutathione levels (beta 45.15 umol/L; 95% CI 5.82, 84.47; P = 0.02)
compared with the placebo. Probiotic supplementation did not affect other
metabolic profiles. Conclusions: Overall, we found that probiotic supplementation
for 12 weeks had beneficial effects on glycemic control, HDL-cholesterol, total
/HDL-cholesterol ratio, biomarkers of inflammation and oxidative stress in
diabetic patients with CHD.Trial registration Clinical trial registration number
http://www.irct.ir: IRCT2017082733941N5.
PMID- 29946369
TI - Unexpected invasion of miniature inverted-repeat transposable elements in viral
genomes.
AB - Background: Transposable elements (TEs) are common and often present with high
copy numbers in cellular genomes. Unlike in cellular organisms, TEs were
previously thought to be either rare or absent in viruses. Almost all reported
TEs display only one or two copies per viral genome. In addition, the discovery
of pandoraviruses with genomes up to 2.5-Mb emphasizes the need for biologists to
rethink the fundamental nature of the relationship between viruses and cellular
life. Results: Herein, we performed the first comprehensive analysis of miniature
inverted-repeat transposable elements (MITEs) in the 5170 viral genomes for which
sequences are currently available. Four hundred and fifty one copies of ten
miniature inverted-repeat transposable elements (MITEs) were found and each MITE
had reached relatively large copy numbers (some up to 90) in viruses. Eight MITEs
belonging to two DNA superfamilies (hobo/Activator/Tam3 and Chapaev-Mirage-CACTA)
were for the first time identified in viruses, further expanding the organismal
range of these two superfamilies. TEs may play important roles in shaping the
evolution of pandoravirus genomes, which were here found to be very rich in
MITEs. We also show that putative autonomous partners of seven MITEs are present
in the genomes of viral hosts, suggesting that viruses may borrow the
transpositional machinery of their cellular hosts' autonomous elements to spread
MITEs and colonize their own genomes. The presence of seven similar MITEs in
viral hosts, suggesting horizontal transfers (HTs) as the major mechanism for
MITEs propagation. Conclusions: Our discovery highlights that TEs contribute to
shape genome evolution of pandoraviruses. We concluded that as for cellular
organisms, TEs are part of the pandoraviruses' diverse mobilome.
PMID- 29946371
TI - Clinical significance of heat shock proteins in gastric cancer following
hyperthermia stress: Indications for hyperthermic intraperitoneal chemoperfusion
therapy.
AB - Heat shock proteins (HSPs) are important factors in the response of cancer cells
to thermo- and chemotherapy. Transient hyperthermic intraperitoneal
chemoperfusion (HIPEC) therapy results in the upregulation of HSP expression,
which may compromise the efficacy of additional anticancer treatments. The aim of
the present study was to monitor the kinetics of HSP expression in tumor cells
and patients with gastric cancer following HIPEC. Thus, in vitro and in vivo
experiments were conducted to investigate the expression of two HSP family
members, HSP70 and HSP90. Cells from two gastric tumor strains were subjected to
HIPEC-mimicking treatment, and HSPs expression was analyzed at specific time
points up to 48 h. Serum HSP concentrations were analyzed in patients with
gastric cancer who had previously received cytoreductive surgery plus HIPEC
treatment. The in vitro experiments indicated a significant elevation of HSP90
expression in gastric adenocarcinoma cells following hyperthermic treatment.
However, HSP70 expression increased from 4 h up to 20 h post-exposure and
decreased to normal levels 36 h post-exposure. Analysis of HSPs in serum samples
collected from 22 patients with gastric cancer confirmed that serum HSP90 and
HSP70 levels increased following HIPEC therapy, peaking at 18 h and returning to
normal 24 h post-exposure. It is therefore advisable to apply the second round of
HIPEC or chemotherapy at least 24 h following the first treatment to minimize any
potential thermoresistance and chemoresistance of tumor cells.
PMID- 29946370
TI - Extensive exchange of transposable elements in the Drosophila pseudoobscura
group.
AB - Background: As species diverge, so does their transposable element (TE) content.
Within a genome, TE families may eventually become dormant due to host-silencing
mechanisms, natural selection and the accumulation of inactive copies. The
transmission of active copies from a TE families, both vertically and
horizontally between species, can allow TEs to escape inactivation if it occurs
often enough, as it may allow TEs to temporarily escape silencing in a new host.
Thus, the contribution of horizontal exchange to TE persistence has been of
increasing interest. Results: Here, we annotated TEs in five species with
sequenced genomes from the D. pseudoobscura species group, and curated a set of
TE families found in these species. We found that, compared to host genes, many
TE families showed lower neutral divergence between species, consistent with
recent transmission of TEs between species. Despite these transfers, there are
differences in the TE content between species in the group. Conclusions: The TE
content is highly dynamic in the D. pseudoobscura species group, frequently
transferring between species, keeping TEs active. This result highlights how
frequently transposable elements are transmitted between sympatric species and,
despite these transfers, how rapidly species TE content can diverge.
PMID- 29946372
TI - Prospective analysis of time out-of-home and objectively measured walking
duration during a week in a large cohort of older adults.
AB - Background: Physical activity is considered an effective measure to promote
health in older people. There is evidence that the number of outdoor trips
increases physical activity by increasing walking duration. The objective of this
study was to analyse the relationship between daily time out-of-home and walking
duration. Furthermore, predictors for walking duration and time out-of-home were
evaluated. Methods: Walking duration was measured prospectively over a 1 week
period by a body-fixed sensor and the time out-of-home was assessed by a
questionnaire at the same days. Seven thousand, two hundred and forty-three days
from 1289 older people (mean age 75.4 years) with both sensor-based measures and
completed questionnaires were included in the analyses. To account for several
observation days per participant multilevel regression analyses were applied.
Analyses were stratified according to the time out-of-home (more or less than 100
min/day). Results: In the group with less than 100 min out-of-home, each
additional minute out-of-home added 20 s to overall walking duration. If the time
exceeded 100 min the additional increase of walking duration was only moderate or
weak. Leaving the home once added 40 min of walking, the following trips 15 to 20
min. Increasing age, lower gait speed, comorbidities, low temperature, rain and
specific week days (Sunday) decreased both the time out-of-home and walking
duration. Other variables like gender (female), isolation or living with a spouse
reduced the time out-of-home without affecting walking duration. Conclusions:
Being out-of-home increases daily walking duration. The association is strongest
if the time out-of-home is 100 min or less.
PMID- 29946373
TI - Assessment of new HDAC inhibitors for immunotherapy of malignant pleural
mesothelioma.
AB - Background: Malignant pleural mesothelioma (MPM) is a very rare and highly
aggressive cancer of the pleura associated in most cases with asbestos exposure.
To date, no really efficient treatments are available for this pathology.
Recently, it has been shown that epigenetic drugs, particularly DNA methylation
or histone acetylation modulating agents, could be very efficient in terms of
cytotoxicity for several types of cancer cells. We previously showed that a
hypomethylating agent (decitabine) and a histone deacetylase inhibitor (HDACi)
(valproic acid (VPA)) combination was immunogenic and led to the induction of an
anti-tumor immune response in a mice model of mesothelioma. However, VPA is not
very specific, is active at millimolar concentrations and is responsible for side
effects in clinic. To improve this approach, we studied four newly synthetized
HDACi, two hydroxamates (ODH and NODH) and two benzamides (ODB and NODB), in
comparison with VPA and SAHA. We evaluated their toxicity on immune cells and
their immunogenicity on MPM cells in combination with decitabine. Results: All
the tested HDACi were toxic for immune cells at high concentrations. Combination
with decitabine increased toxicity of HDACi only towards T-cell clone. A decrease
in the proportion of regulatory T cells and natural killer cells was observed in
particular with VPA and ODH. In MPM cells, all HDACi combinations induced NY-ESO
1 cancer testis antigen (CTA) expression and the recognition of the treated cells
by a NY-ESO-1 specific T-CD8 clone. However, for MAGE-A1, MAGE-A3 and XAGE-1b
mRNA expression, the results obtained depended on the HDACi used and on the CTA
studied. Depending on the MPM cell line studied, molecules alone increased
moderately PD-L1 expression. When combined, a higher stimulation of this immune
check point inhibitor expression was observed. Decitabine-induced anti-viral
response seemed to be inhibited in the presence of HDACi. Conclusions: This work
shows that the combination of decitabine and HDACi could be of interest for MPM
immunotherapy. However, this combination induced PD-L1 expression which suggests
that an association with anti-PD-L1 therapy should be performed to induce an
efficient anti-tumor immune response.
PMID- 29946375
TI - Differentially methylated regions in T cells identify kidney transplant patients
at risk for de novo skin cancer.
AB - Background: Cutaneous squamous cell carcinoma (cSCC) occurs 65-200 times more in
immunosuppressed organ transplant patients than in the general population. T
cells, which are targeted by the given immunosuppressive drugs, are involved in
anti-tumor immune surveillance and are functionally regulated by DNA methylation.
Prior to kidney transplantation, we aim to discover differentially methylated
regions (DMRs) in T cells involved in de novo post-transplant cSCC development.
Methods: We matched 27 kidney transplant patients with a future de novo cSCC
after transplantation to 27 kidney transplant patients without cSCC and studied
genome-wide DNA methylation of T cells prior to transplantation. From 11 out of
the 27 cSCC patients, the DNA methylation of T cells after transplantation was
also examined to assess stability of the observed differences in DNA methylation.
Raw methylation values obtained with the 450k array were confirmed with
pyrosequencing. Results: We found 16 DMRs between patients with a future cSCC and
those who do not develop this complication after transplantation. The majority of
the DMRs were located in regulatory genomic regions such as flanking bivalent
transcription start sites and bivalent enhancer regions, and most of the DMRs
contained CpG islands. Examples of genes annotated to the DMRs are ZNF577, coding
for a zinc-finger protein, and FLOT1, coding for a protein involved in T cell
migration. The longitudinal analysis revealed that DNA methylation of 9 DMRs
changed significantly after transplantation. DNA methylation of 5 out of 16 DMRs
was relatively stable, with a variation in beta-value lower than 0.05 for at
least 50% of the CpG sites within that region. Conclusions: This is the first
study demonstrating that DNA methylation of T cells from patients with a future
de novo post-transplant cSCC is different from patients without cSCC. These
results were obtained before transplantation, a clinically relevant time point
for cSCC risk assessment. Several DNA methylation profiles remained relatively
stable after transplantation, concluding that these are minimally affected by the
transplantation and possibly have a lasting effect on post-transplant cSCC
development.
PMID- 29946376
TI - Job Roles of the 2025 Medical Educator.
PMID- 29946377
TI - Branding and Recruitment: A Primer for Residency Program Leadership.
PMID- 29946374
TI - rs10732516 polymorphism at the IGF2/H19 locus associates with genotype-specific
effects on placental DNA methylation and birth weight of newborns conceived by
assisted reproductive technology.
AB - Background: Assisted reproductive technology (ART) has been associated with low
birth weight of fresh embryo transfer (FRESH) derived and increased birth weight
of frozen embryo transfer (FET)-derived newborns. Owing to that, we focused on
imprinted insulin-like growth factor 2 (IGF2)/H19 locus known to be important for
normal growth. This locus is regulated by H19 imprinting control region (ICR)
with seven binding sites for the methylation-sensitive zinc finger regulatory
protein (CTCF). A polymorphism rs10732516 G/A in the sixth binding site for CTCF,
associates with a genotype-specific trend to the DNA methylation. Due to this
association, 62 couples with singleton pregnancies derived from FRESH (44 IVF/18
ICSI), 24 couples from FET (15 IVF/9 ICSI), and 157 couples with spontaneously
conceived pregnancies as controls were recruited in Finland and Estonia for
genotype-specific examination. DNA methylation levels at the H19 ICR, H19 DMR,
and long interspersed nuclear elements in placental tissue were explored by
MassARRAY EpiTYPER (n = 122). Allele-specific changes in the methylation level of
H19 ICR in placental tissue (n = 26) and white blood cells (WBC, n = 8) were
examined by bisulfite sequencing. Newborns' (n = 243) anthropometrics was
analyzed by using international growth standards. Results: A consistent trend of
genotype-specific decreased methylation level was observed in paternal allele of
rs10732516 paternal A/maternal G genotype, but not in paternal G/maternal A
genotype, at H19 ICR in ART placentas. This hypomethylation was not detected in
WBCs. Also genotype-specific differences in FRESH-derived newborns' birth weight
and head circumference were observed (P = 0.04, P = 0.004, respectively): FRESH
derived newborns with G/G genotype were heavier (P = 0.04) and had larger head
circumference (P = 0.002) compared to newborns with A/A genotype. Also, the
placental weight and birth weight of controls, FRESH- and FET-derived newborns
differed significantly in rs10732516 A/A genotype (P = 0.024, P = 0.006,
respectively): the placentas and newborns of FET-derived pregnancies were heavier
compared to FRESH-derived pregnancies (P = 0.02, P = 0.004, respectively).
Conclusions: The observed DNA methylation changes together with the phenotypic
findings suggest that rs10732516 polymorphism associates with the effects of ART
in a parent-of-origin manner. Therefore, this polymorphism should be considered
when the effects of environmental factors on embryonic development are studied.
PMID- 29946378
TI - Legal Considerations in the Remediation and Dismissal of Graduate Medical
Trainees.
PMID- 29946379
TI - Cultivating Global Surgery Initiatives Abroad and at Home.
PMID- 29946381
TI - Letters of Recommendation: How Do They Fit Into the Modern Application?
PMID- 29946380
TI - Dear Program Director: Deciphering Letters of Recommendation.
AB - Background : Letters of recommendation (LORs) are an important part of
applications for residency and fellowship programs. Despite anecdotal use of a
"code" in LORs, research on program director (PD) perceptions of the value of
these documents is sparse. Objective : We analyzed PD interpretations of LOR
components and discriminated between perceived levels of applicant
recommendations. Methods : We conducted a cross-sectional, descriptive study of
pediatrics residency and fellowship PDs. We developed a survey asking PDs to rate
3 aspects of LORs: 13 letter features, 10 applicant abilities, and 11 commonly
used phrases, using a 5-point Likert scale. The 11 phrases were grouped using
principal component analysis. Mean scores of components were analyzed with
repeated-measures analysis of variance. Median Likert score differences between
groups were analyzed with Mann-Whitney U tests. Results : Our survey had a 43%
response rate (468 of 1079). "I give my highest recommendation" was rated the
most positive phrase, while "showed improvement" was rated the most negative.
Principal component analysis generated 3 groups of phrases with moderate to
strong correlation with each other. The mean Likert score for each group from the
PD rating was calculated. Positive phrases had a mean (SD) of 4.4 (0.4), neutral
phrases 3.4 (0.5), and negative phrases 2.6 (0.6). There was a significant
difference among all 3 pairs of mean scores (all P < .001). Conclusions :
Commonly used phrases in LORs were interpreted consistently by PDs and influenced
their impressions of candidates. Key elements of LORs include distinct phrases
depicting different degrees of endorsement.
PMID- 29946383
TI - Proceed With Caution: Implementing Competency-Based Graduate Medical Education.
PMID- 29946382
TI - Preliminary Validity Evidence for a Milestones-Based Rating Scale for Chart
Stimulated Recall.
AB - Background : Minimally anchored Standard Rating Scales (SRSs), which are widely
used in medical education, are hampered by suboptimal interrater reliability.
Expert-derived frameworks, such as the Accreditation Council for Graduate Medical
Education (ACGME) Milestones, may be helpful in defining level-specific anchors
to use on rating scales. Objective : We examined validity evidence for a
Milestones-Based Rating Scale (MBRS) for scoring chart-stimulated recall (CSR).
Methods : Two 11-item scoring forms with either an MBRS or SRS were developed.
Items and anchors for the MBRS were adapted from the ACGME Internal Medicine
Milestones. Six CSR standardized videos were developed. Clinical faculty scored
videos using either the MBRS or SRS and following a randomized crossover design.
Reliability of the MBRS versus the SRS was compared using intraclass correlation.
Results : Twenty-two faculty were recruited for instrument testing. Some
participants did not complete scoring, leaving a response rate of 15 faculty (7
in the MBRS group and 8 in the SRS group). A total of 529 ratings (number of
items * number of scores) using SRSs and 540 using MBRSs were available. Percent
agreement was higher for MBRSs for only 2 of 11 items-use of consultants (92
versus 75, P = .019) and unique characteristics of patients (96 versus 79, P =
.011)-and the overall score (89 versus 82, P < .001). Interrater agreement was
0.61 for MBRSs and 0.51 for SRSs. Conclusions : Adding milestones to our rating
form resulted in significant, but not substantial, improvement in intraclass
correlation coefficient. Improvement was inconsistent across items.
PMID- 29946384
TI - Assessing Residents' Veteran-Centered Care Skills in the Clinical Setting.
AB - Background : Despite their placement in Veterans Health Administration centers
nationwide, residents' training and assessment in veteran-centered care is
variable and often insufficient. Objective : We assessed residents' ability to
recognize and address mental health issues that affect US military veterans.
Methods : Two unannounced standardized patient (SP) cases were used to assess
internal medicine residents' veteran-centered care skills from September 2014 to
March 2016. Residents were assessed on 7 domains: military history taking,
communication skills, assessment skills, mental health screening, triage, and
professionalism, using a 36-item checklist. After each encounter, residents
completed a questionnaire to assess their ability to recognize knowledge
deficits. Residents' mean scores were compared across training levels, between
the 2 cases, and by SP gender. We conducted analysis of variance (ANOVA) tests to
analyze mean performance differences across training levels and descriptive
statistics to analyze self-assessment questionnaire results. Results : Ninety
eight residents from 2 internal medicine programs completed the encounter and 53
completed the self-assessment questionnaire. Residents performed best on
professionalism (0.92 +/- 0.20, percentage of the maximal score) and triage (0.87
+/- 0.17), and they scored lowest on posttraumatic stress disorder (0.52 +/-
0.30) and military sexual trauma (0.33 +/- 0.39). Few residents reported that
they sought out training to enhance their knowledge and skills in the provision
of services and support to military and veteran groups beyond their core
curriculum. Conclusions : This study suggests that additional education and
assessment in veteran-centered care may be needed, particularly in the areas of
posttraumatic stress disorder and military sexual trauma.
PMID- 29946385
TI - Using Unannounced Standardized Patients to Explore Variation in Care for Patients
With Depression.
AB - Background : Physicians across specialties need to be skilled at diagnosing and
treating depression, yet studies show underrecognition and inadequate treatment.
Understanding the reasons requires specifying the influence of patient
presentation, screening, and physician competence. Objective : We deployed an
unannounced standardized patient (SP) case to assess clinic screening and
internal medicine (IM) residents' practices in identifying, documenting, and
treating depression. Methods : The SP represented a new patient presenting to the
outpatient clinic, complaining of fatigue, with positive Patient Health
Questionnaire (PHQ) items 2 and 9 and a family history of depression. The SPs
assessed clinic screening and IM resident practices; appropriate treatment was
assessed through chart review and defined as the resident doing at least 1 of the
following: prescribing a selective serotonin reuptake inhibitor (SSRI), making a
referral, or scheduling a 2-week follow-up. Results : Of 129 IM residents, 85
(66%) provided appropriate treatment, 79 (61%) appropriately referred, 59 (46%)
prescribed an SSRI, and 49 (38%) scheduled a 2-week follow-up, while 40 (31%) did
not add depression to the problem list. The IM residents who used PHQ-2 and PHQ-9
were more likely to appropriately (89%) versus inappropriately (50%) treat (P <
.001). Compared with those who did not, residents who treated appropriately
assessed depression symptoms more (P < .001) and had better communication (73%
versus 50%, P = .02), patient centeredness (74% versus 42%, P = .03), and patient
activation skills (35% versus 11%, P < .001). Conclusions : The use of
unannounced SPs helps identify targets for training residents to provide evidence
based treatment of depression.
PMID- 29946387
TI - Effect of Trainee Performance Data on Standard-Setting Judgments Using the
Mastery Angoff Method.
AB - Background : Mastery learning in health professions education requires learners
to learn and undergo assessment until they demonstrate a high level of
competence. Setting defensible standards is key to accurately assessing
educational outcomes in mastery learning. The Mastery Angoff method was proposed
recently to set a minimum passing standard (MPS) for mastery learning curricula.
However, it is unknown whether prior knowledge of trainee performance affects
judges' decisions about setting an MPS using the Mastery Angoff method. Objective
: We sought to determine the effect of introducing baseline data about trainee
performance on faculty judges' decisions about the Mastery Angoff MPS for a
written examination. Methods : We developed a mastery learning curriculum to
train internal medicine residents and cardiology fellows about the correct
interpretation of inpatient telemetry monitoring. All learners were required to
meet or exceed an MPS on a 35-item written examination at the end of training.
The MPS was set in 2017 by judges who used the item-based Mastery Angoff method
without prior examinee performance information. The judges subsequently
reevaluated the test items after receiving baseline data about trainee
performance collected during pilot testing. Mastery Angoff MPSs with and without
baseline performance data were compared. Results : Twelve judges participated in
the standard-setting exercise. The initial MPS was similar to the repeat MPS set
after judges received trainee performance data (86.2% versus 86.9%, P = .23).
Conclusions : Prior knowledge about medical trainee performance data did not
affect MPS as determined by the Mastery Angoff procedure.
PMID- 29946386
TI - Open Notes in Teaching Clinics: A Multisite Survey of Residents to Identify
Anticipated Attitudes and Guidance for Programs.
AB - Background : Clinicians are increasingly sharing outpatient visit notes with
patients through electronic portals. These open notes may bring about new
educational opportunities as well as concerns to physicians-in-training and
residency programs. Objective : We assessed anticipatory attitudes about open
notes and explored factors influencing residents' propensity toward note
transparency. Methods : Residents in primary care clinics at 4 teaching hospitals
were surveyed prior to implementation of open notes. Main measures included
resident attitudes toward open notes and the anticipated effect on patients,
resident workload, and education. Data were stratified by site. Results : A total
of 176 of 418 (42%) residents responded. Most residents indicated open notes
would improve patient engagement, trust, and education but worried about
overwhelming patients, residents being less candid, and workload. More than half
of residents thought open notes were a good idea, and 32% (56 of 176) indicated
they would encourage patients to read these notes. More than half wanted note
writing education and more feedback, and 72% (126 of 175) indicated patient
feedback on residents' notes could improve communication skills. Attitudes about
effects of open notes on safety, quality, trust, and medical education varied by
site. Conclusions : Residents reported mixed feelings about the anticipated
effects of sharing clinical notes with patients. They advocate for patient
feedback on notes, yet worry about workload, supervision, and errors. Training
site was correlated with many attitudes, suggesting local culture drives resident
support for open notes. Strategies that address resident concerns and promote
teaching and feedback related to notes may be helpful.
PMID- 29946388
TI - Experiential Communications Curriculum to Improve Resident Preparedness When
Responding to Discriminatory Comments in the Workplace.
AB - Background : Patients and families can make discriminatory comments leading to
physician distress. Residents receive little training in appropriate responses to
such comments and may be ill equipped to respond to intolerance without
alienating the individual(s) making the comments. Objective : We assessed whether
a simulated curriculum would enhance pediatrics residents' ability to effectively
respond to discriminatory comments. Methods : In the 2016-2017 academic year, we
modified an existing communication skills curriculum for senior pediatrics
residents. Residents engaged a simulated parent who used discriminatory speech in
4 scenarios, followed by a group debriefing. We conducted anonymous surveys to
assess residents' preparedness to respond to these comments before and
immediately following participation and examined their experience with
discriminatory comments in the workplace. Results : The majority of residents
reported prior experience with discriminatory comments (32 of 45 [71%] witnessed
such comments, and 27 of 48 [56%] were targeted by such comments), most often
regarding age, race, and ethnicity. Mean precourse scores ranged from 2.1 to 3.1
(on a 5-point scale) regarding ability to engage in a firm yet respectful
dialogue, to reference the hospital code of conduct, to coach a learner to
respond, and to facilitate a team debrief. Mean postcourse scores improved
significantly for these questions (range 3.8-4.1). The greatest improvement was
in referencing the code of conduct (2.1 versus 4.0, P < .001). Conclusions :
Immediately after participating in simulation, pediatrics residents reported a
significant improvement in self-reported readiness to respond to discriminatory
comments made by a parent and reported the simulation experience was beneficial.
PMID- 29946389
TI - Project ECHO-Geriatrics: Training Future Primary Care Providers to Meet the Needs
of Older Adults.
AB - Background : Geriatrics training is essential for future primary care providers.
The Extension for Community Healthcare Outcomes (ECHO) model improves access to
specialty care via case-based videoconferencing, but Project ECHO has not
previously been designed to target residents. Objective : We designed Project
ECHO-Geriatrics to deliver geriatrics education to primary care trainees using
the ECHO model and evaluated self-rated geriatrics competency of trainees from
the University of Washington Family Medicine Residency Network programs who
participated between January 2016 and March 2017. Methods : We assessed outcomes
of Project ECHO-Geriatrics through anonymous surveys. Participants rated
didactics, case discussions, and geriatrics-specific knowledge before and after
sessions on a 5-point scale (1, low, to 5, high). Participants were asked whether
they planned to do anything differently in their practice and, if yes, to
describe this change. Results : Fifteen sessions were held with 204 unique
participants from 12 sites, with an average of 28 (range, 13-41) participants per
session. From the 9 of 29 (31%) Family Medicine Residency Network programs that
enrolled, 63% percent (116 of 184) of eligible residents attended. Sessions were
highly rated (89% of responses were 4 or 5). Self-reported geriatrics-specific
knowledge increased significantly (before 3.3 [SD = 0.89] versus after 4.0 [SD =
0.60], P < .001). Sixty-five percent (118 of 181) of participants reported plans
to change their practice. Conclusions : Project ECHO-Geriatrics is an innovative,
feasible way to train the future primary care workforce in geriatrics and grow
the capacity to provide high-quality care to older adults.
PMID- 29946390
TI - X + Y = Time for QI: Meaningful Engagement of Residents in Quality Improvement
During the Ambulatory Block.
AB - Background : Meaningful resident engagement in quality improvement (QI) remains
challenging. Barriers include a lack of time and of faculty with QI expertise. We
leveraged our internal medicine (IM) residency program's adoption of an "X"
(inpatient rotations) plus "Y" (ambulatory block) schedule to implement a QI
curriculum for all residents during their ambulatory block. Objective : We sought
to engage residents in interprofessional QI, improve residents' QI confidence and
knowledge and application to practice, and create opportunities for QI
scholarship. Methods : In July 2015, the program provided dedicated time for QI
in the ambulatory block. All categorical IM residents and 11 voluntary faculty
mentors were divided into 10 teams based on clinic site and "Y" block schedule.
Teams participated in resident-led, interprofessional ambulatory QI projects.
Resident QI knowledge and confidence were assessed before the curriculum and 11
months after using the Quality Improvement Knowledge Application Tool-Revised
(QIKAT-R) and surveys. QI project implementation and scholarship were tracked.
Results : All categorical residents (N = 81) participated. Residents reported
increased confidence in all QI skills, and they demonstrated increased knowledge,
with mean QIKAT-R paired scores improving from 15.8 +/- 4.6 to 19.1 +/- 5.9 (n =
45 pairs, P < .001). A total of 9 of 10 teams implemented process changes, and 6
team project improvements have been sustained. Conclusions : This ongoing
curriculum engaged IM and IM-psychiatry residents in QI during their ambulatory
block using volunteer clinic faculty mentors. Residents demonstrated improved QI
confidence and knowledge. The majority of resident projects were sustained and
generated scholarship.
PMID- 29946391
TI - Simple Frameworks for Daily Work: Innovative Strategies to Coach Residents
Struggling With Time Management, Organization, and Efficiency.
AB - Background : Organization and efficiency are central to success on busy inpatient
services and may be relevant to demonstrating certain milestones. Most residents
adopt these skills by observing supervisors and peers. For some, this method of
emulation and adaptation does not occur, with the potential for a negative effect
on patient care and team morale. Information on effective strategies for
remediating organization and efficiency deficits is lacking. Objective : We
explored the major themes of organization and efficiency referred to the
University of Pennsylvania Department of Medicine Early Intervention and
Remediation Committee (EIRC), and developed tools for their remediation. Methods
: Assessments of residents and fellows referred to the EIRC between July 2014 and
October 2016 were reviewed for organization and efficiency deficits. Common areas
were identified, and an iterative process of learner observations and expert
input was used to develop remediation tools. Results : Over a 2-year period, the
EIRC developed remediation plans for 4% of residents (13 of 342 total residents),
and for 1 internal medicine subspecialty fellow. Organization and efficiency was
the primary or secondary deficit in more than half of those assessed. Most common
deficiencies involved admitting a patient efficiently, performing effective
prerounding, and composing daily progress notes/presentations. Remediation tools
that provided deconstruction of tasks to their most granular and reproducible
components were effective in improving performance. Conclusions : Deficits in
organization and efficiency can disproportionately affect resident performance
and delay milestone achievement. Many residents would benefit from detailed
frameworks and assistance with new approaches to basic elements of daily work.
PMID- 29946393
TI - Trusting Your Test Results: Building and Revising Multiple-Choice Examinations.
PMID- 29946392
TI - Developing an Assessment Framework for Essential Internal Medicine Subspecialty
Topics.
AB - Background : Assessing residents by direct observation is the preferred
assessment method for infrequently encountered subspecialty topics, but this is
logistically challenging. Objective : We developed an assessment framework for
internal medicine (IM) residents in subspecialty topics, using tuberculosis
diagnosis for proof of concept. Methods : We used a 4-step process at 8 academic
medical centers that entailed (1) creating a 10-item knowledge assessment tool;
(2) pilot testing on a sample of 129 IM residents and infectious disease fellow
volunteers to evaluate validity evidence; (3) implementing the final tool among
886 resident volunteers; and (4) assessing outcomes via retrospective chart
review. Outcomes included tool score, item performance, and rates of obtaining
recommended diagnostics. Results : Following tool development, 10 infectious
disease experts provided content validity. Pilot testing showed higher mean
scores for fellows compared with residents (7 [SD = 1.8] versus 3.8 [SD = 1.7],
respectively, P < .001) and a satisfactory Kuder-Richardson Formula 20 (0.72).
Implementation of the tool revealed a 14-minute (SD = 2.0) mean completion time,
61% (541 of 886) response rate, 4.4 (SD = 1.6) mean score, and <= 57% correct
response rate for 9 of 10 items. On chart review (n = 343), the rate of obtaining
each recommended test was <= 43% (113 of 261), except for chest x-rays (96%, 328
of 343). Conclusions : Our assessment framework revealed knowledge and practice
gaps in tuberculosis diagnosis in IM residents. Adopting this approach may help
ensure assessment is not limited to frequently encountered topics.
PMID- 29946394
TI - Graduate Medical Education Still Needs New Ideas.
PMID- 29946395
TI - Through the Learner's Lens: Eye-Tracking Augmented Debriefing in Medical
Simulation.
PMID- 29946396
TI - A Daily Dose of Humanities.
PMID- 29946397
TI - Si, Tu Puedes: An Integrated Spanish Language Acquisition in Residency Utilizing
Personal Instruction.
PMID- 29946398
TI - Turning Mortality Discussions Into Process Improvements.
PMID- 29946399
TI - Cognitive Autopsy: A Transformative Group Approach to Mitigate Cognitive Bias.
PMID- 29946400
TI - A Culture of Safety From Day 1: An Institutional Patient Safety Initiative to
Support Incoming Interns.
PMID- 29946401
TI - How to Make It Real: Disparities of Care Experiential Learning Workshop.
PMID- 29946403
TI - A Case-Based Method for New Resident Orientation.
PMID- 29946402
TI - Utilizing Employee Assistance Programs for Resident Wellness.
PMID- 29946404
TI - Tackling Implicit and Explicit Bias Through Objective Structured Teaching
Exercises for Faculty.
PMID- 29946405
TI - Feedback on Feedback as a Faculty Development Tool.
PMID- 29946406
TI - Educational Courage: Conquering Our Cowardly Lion.
PMID- 29946407
TI - Sharing Failure: Reflections of a Chief Resident.
PMID- 29946408
TI - A Gift to My Intern.
PMID- 29946409
TI - Wellness Opportunities: Sometimes It Is "Just Time Off".
PMID- 29946410
TI - Teaching Health Centers Can Meet Objectives for State Medicaid Innovation.
PMID- 29946411
TI - Milestones 2.0: A Step Forward.
PMID- 29946412
TI - Perspectives of a Back to Bedside Reviewer.
PMID- 29946413
TI - Intensity output and effectiveness of light curing units in dental offices.
AB - Background: The aims of the study were measuring the light intensity of light
curing units used in Qazvin's dental offices, determining the relationship
between the clinical age of these units and their light intensity, and
identifying the reasons for repairing them. Material and Methods: In this cross
sectional study, the output intensity of 95 light curing devices was evaluated
using a radiometer. The average output intensity was divided up into four
categories (less than 200, 200-299, 300-500, and more than 500 mW/cm2). In
addition, a questionnaire was designed to obtain information mainly about the
type, clinical age, and frequency of maintenance of the units and the reasons for
fixing them. Data were analyzed using Kolmogorov-Smirnov, chi-squared, and t
tests (p< 0.05) on SPSS 24. Results: A total of 95 light curing units were
examined, with 61 (64.2%) of them being of the LED type and 34 (35.8%) of the QTH
type. While average light intensity in LED units was significantly higher than in
QTH devices, the two device types were not significantly different regarding
desirable light intensity (i.e., >= 300 mw/cm2). A negative correlation was
observed between clinical age and light intensity. In addition, bulb replacement
in QTH devices was over three times as much as in LED units. Also, repairing QTHs
was more than twice as much frequent as fixing LEDs. The most common reason for
repair was the breakage of the tip of the device. Conclusions: The light
intensity of LED units is significantly higher than that of QTH devices, and the
frequency of repairing in QTHs was significantly more than in LEDs. Furthermore,
light intensity decreases with aging, and dentists should regularly monitor the
conditions of light units. Key words:Light curing unit, radiometer, light
intensity, dental equipment, dental offices.
PMID- 29946414
TI - Satisfaction in complete denture wearers with and without adhesives: A
randomized, crossover, double-blind clinical trial.
AB - Background: The purpose of this study was to compare the satisfaction of patients
regarding retention, stability and accumulation of particles with a randomized,
double-blind crossed method in users with complete dentures with and without
adhesive. Material and Methods: Seventeen edentulous individuals were randomized
and received new upper and lower complete dentures. After a period of adaptation,
they participated in some masticatory tests and clinical revisions, after use the
protheses with and without the use of two denture adhesives: Adhesive A
(Fittydent, Fittydent International GmbH) and adhesive B (Corega,
GlaxoSmithKline) at 0, 7 and 14 days. Satisfaction was measured immediately after
each test through a survey using a VAS scale (0-10) and data were analyzed with
McNemar's test with Bonferroni correction. Results: The results showed
significant differences (p<.01) between the study groups with adhesive A - B and
the group without adhesive, but no significant differences were found between the
two stickers for any of the variables studied. Conclusions: Complete denture
adhesives significantly improved the satisfaction of patients because a better
retention, stability and less accumulation of particles of the food substitute
between the denture and the mucosa is obtained compared with non-use of complete
denture adhesives. Key words:Complete dentures, patient satisfaction, denture
adhesives, clinical trials.
PMID- 29946417
TI - Epidemiology of spider mite sensitivity: a meta-analysis and systematic review.
AB - Background: Spider mites, including Tetranychus urticae, Panonychus citri, and
Panonychus ulmi, are common pests in gardens, greenhouses, and orchards.
Exposure, particularly occupational exposure, to these organisms may lead to the
development of respiratory or contact allergies. However, the prevalence of
sensitivity to spider mites is unclear. Methods: We examined the literature to
generate an estimate of the global prevalence of allergies to spider mites.
Results: Electronic databases were searched and twenty-three studies reporting
the prevalence of sensitivity to spider mites (based on skin prick tests or IgE
based detection systems) in an aggregate total of 40,908 subjects were selected
for analysis. The estimated overall rate of spider mite sensitivity was 22.9%
(95% CI 19-26.8%). Heterogeneity was high and meta-regression analysis
considering variables such as published year, country, number of study subjects,
methods for allergen detection (skin prick test, ImmunoCAP, RAST testing, or
intradermal test), and mite species revealed no single significant source. Twelve
of the 23 studies reported rates of monosensitization (i.e., patients responsive
to spider mites but no other tested allergen), yielding a global average of 7%
(95% CI 5-9%), hence spider mites represent a unique source of allergens.
Conclusions: Spider mites are an important cause of allergic symptoms. However,
the publication bias and heterogeneity evident in this study indicate that
further trials using standardized detection methods are needed to determine the
association of exposure and symptoms as well as the specific patient
characteristics that influence developing spider mite sensitivity.
PMID- 29946415
TI - Sociability deficits after prenatal exposure to valproic acid are rescued by
early social enrichment.
AB - Background: Autism spectrum disorder (ASD) is characterized by impaired social
interactions and repetitive patterns of behavior. Symptoms appear in early life
and persist throughout adulthood. Early social stimulation can help reverse some
of the symptoms, but the biological mechanisms of these therapies are unknown. By
analyzing the effects of early social stimulation on ASD-related behavior in the
mouse, we aimed to identify brain structures that contribute to these behaviors.
Methods: We injected pregnant mice with 600-mg/kg valproic acid (VPA) or saline
(SAL) at gestational day 12.5 and evaluated the effect of weaning their offspring
in cages containing only VPA animals, only SAL animals, or mixed. We analyzed
juvenile play at PD21 and performed a battery of behavioral tests in adulthood.
We then used preclinical PET imaging for an unbiased analysis of the whole brain
of these mice and studied the function of the piriform cortex by c-Fos
immunoreactivity and HPLC. Results: Compared to control animals, VPA-exposed
animals play less as juveniles and exhibit a lower frequency of social
interaction in adulthood when reared with other VPA mice. In addition, these
animals were less likely to investigate social odors in the
habituation/dishabituation olfactory test. However, when VPA animals were weaned
with control animals, these behavioral alterations were not observed.
Interestingly, repetitive behaviors and depression-related behaviors were not
affected by social enrichment. We also found that VPA animals present high levels
of glucose metabolism bilaterally in the piriform cortex (Pir), a region known to
be involved in social behaviors. Moreover, we found alterations in the
somatosensory, motor, and insular cortices. Remarkably, these effects were mostly
reversed after social stimulation. To evaluate if changes in glucose metabolism
in the Pir correlated with changes in neuronal activity, we measured c-Fos
immunoreactivity in the Pir and found it increased in animals prenatally exposed
to VPA. We further found increased dopamine turnover in the Pir. Both alterations
were largely reversed by social enrichment. Conclusions: We show that early
social enrichment can specifically rescue social deficits in a mouse model of
ASD. Our results identified the Pir as a structure affected by VPA-exposure and
social enrichment, suggesting that it could be a key component of the social
brain circuitry.
PMID- 29946418
TI - Survey of chiropractic clinicians on self-reported knowledge and recognition of
concussion injuries.
AB - Background: There has been little study of the recognition of mild traumatic
brain injury (MTBI) by the chiropractic practitioner, or of the inquiry by the
clinician to assess those patients who may be suffering from the condition, but
fail to report the symptoms. Although severe cases of TBI are more often
recognized and treated by attendance to hospital or emergency room, MTBI is less
recognizable and would present a long-term risk to the patient. Given the
clinical risk associated with failure to recognize such injuries, training of the
clinician in the subtle signs of MTBI is imperative. What we currently know about
training in the recognition of MTBI is from limited recent knowledge based
studies. This study is intended to assess the self-reported mild traumatic brain
injury (MTBI) knowledge, recognition and treatment by chiropractic practitioners.
Methods: A previously published standardized set of survey items was distributed
to a captive audience of chiropractic practitioners at the July 2016 Texas
Chiropractic College annual symposium. The sample population was a convenience
sample of chiropractic clinicians who were assessed for MTBI knowledge and common
practices. Results: There was a response rate of 43% of the 125 attendees. The
survey demonstrated confidence in MTBI diagnosis. Average MTBI knowledge and
recognition score was only 27% +/- 22%. Frequency of MTBI patients presenting to
the chiropractic clinician office was an average of less than one per month.
Sixty nine percent (69%) of the clinicians relied upon their history and clinical
exam for diagnosis. There was no knowledge of the Balance Error Scoring system
and only 20% utilized the Standardized Concussion Assessment Tool (SCAT). The
primary action of the chiropractic clinician who suspected MTBI was to refer to a
neurological specialist (76%). A small minority of practitioners would provide
treatment. Conclusions: There is an overconfidence of the chiropractic
practitioner in recognition of MTBI which is incongruent with the low knowledge
scores. Further education of the chiropractic clinician is warranted. Trial
registration: University Hospital Medical Information Network Clinical Trials
Registry. Retrospectively registered (UMIN-CTR), trial number: UMIN#000029744
(Receipt# R000033980) data: October 27, 2017.Date of enrollment 7/14/2016.
PMID- 29946419
TI - Key actors in driving behavioural change in relation to on-farm biosecurity; a
Northern Ireland perspective.
AB - Background: Agriculture and farming are valued contributors to local economy in
Northern Ireland (NI). There is limited knowledge about farmers' behaviours and
attitudes towards disease biosecurity measures. As part of a larger project, a
scenario-based workshop with key stakeholders was organised by the Agri-Food and
Biosciences Institute (AFBI)-NI in December 2015. Results: A total of 22
participants belonging to 12 different institutions took part in the workshop.
Participants were presented with an overview of previously conducted biosecurity
research in NI and England. In small groups, participants were subsequently asked
to discuss and give their opinions about a series of questions across four key
areas in a semi-structured approach with an external facilitator. The key areas
were 1- disease risk perception at the farm level; 2-perceived barriers to
implementing on farm biosecurity measures; 3- avenues to successful behaviour
change and 4-key industry responsibilities and roles. The discussion showed that
training in biosecurity for farmers is important and necessary. Training was
recommended to be provided by veterinary surgeons, preferably via a face-to-face
format. The discussion addressing disease disclosure proved particularly
challenging between those who were prospective buyers of cattle, and those who
sold cattle. Conclusions: This workshop provided a unique and invaluable insight
into key issues regarding farm level biosecurity activities. From a policy
perspective, delivering improved on-farm biosecurity must be addressed via a
multidisciplinary approach. This can only be achieved with active involvement,
commitment and support of a number of key industry and government stakeholders.
PMID- 29946416
TI - Creating diversity in mammalian facial morphology: a review of potential
developmental mechanisms.
AB - Mammals (class Mammalia) have evolved diverse craniofacial morphology to adapt to
a wide range of ecological niches. However, the genetic and developmental
mechanisms underlying the diversification of mammalian craniofacial morphology
remain largely unknown. In this paper, we focus on the facial length and
orofacial clefts of mammals and deduce potential mechanisms that produced
diversity in mammalian facial morphology. Small-scale changes in facial
morphology from the common ancestor, such as slight changes in facial length and
the evolution of the midline cleft in some lineages of bats, could be attributed
to heterochrony in facial bone ossification. In contrast, large-scale changes of
facial morphology from the common ancestor, such as a truncated, widened face as
well as the evolution of the bilateral cleft possessed by some bat species, could
be brought about by changes in growth and patterning of the facial primordium
(the facial processes) at the early stages of embryogenesis.
PMID- 29946420
TI - Study of oral aniracetam in C57BL/6J mice without pre-existing cognitive
impairments.
AB - BACKGROUND: The piracetam analog, aniracetam, has recently received attention for
its cognition enhancing potential, with minimal reported side effects. Previous
studies report the drug to be effective in both human and non-human models with
pre-existing cognitive dysfunction, but few studies have evaluated its efficacy
in healthy subjects. A previous study performed in our laboratory found no
cognitive enhancing effects of oral aniracetam administration 1-hour prior to
behavioral testing in naive C57BL/6J mice. METHODS: The current study aims to
further evaluate this drug by administration of aniracetam 30 minutes prior to
testing in order to optimize any cognitive enhancing effects. In this study, all
naive C57BL/6J mice were tested in tasks of delayed fear conditioning, novel
object recognition, rotarod, open field, elevated plus maze, and marble burying.
RESULTS: Across all tasks, animals in the treatment group failed to show enhanced
learning when compared to controls. CONCLUSIONS: These results provide further
evidence suggesting that aniracetam conveys no therapeutic benefit to subjects
without pre-existing cognitive dysfunction.
PMID- 29946421
TI - The unhappy postdoc: a survey based study.
AB - Background: The emerging public discourse about the "broken" postdoc system is
mostly conceptual. The current work offers an attempt to quantify postdocs'
perceptions, goals, and well-being. Methods: A survey of 190 postdocs in North
America. Results: This article first reveals a surprisingly unhappy postdoc
community with low satisfaction with life scores. Second, it demonstrates how
over the course of the fellowship many postdocs lose interest in the goal of
pursuing a tenure track academic position (~20%) or in recommending the postdoc
track to others (~30%). Finally, we find that among a large number of factors
that can enhance satisfaction with life for postdocs (e.g., publication
productivity, resources available to them) only one factor stood out as
significant: the degree to which atmosphere in the lab is pleasant and collegial.
Conclusions: Our findings can stimulate policy, managerial, and career
development improvements in the context of the postdoc system.
PMID- 29946422
TI - Simulation and visualization of multiple KEGG pathways using BioNSi.
AB - Motivation: Many biologists are discouraged from using network simulation tools
because these require manual, often tedious network construction. This situation
calls for building new tools or extending existing ones with the ability to
import biological pathways previously deposited in databases and analyze them, in
order to produce novel biological insights at the pathway level. Results: We have
extended a network simulation tool (BioNSi), which now allows merging of multiple
pathways from the KEGG pathway database into a single, coherent network, and
visualizing its properties. Furthermore, the enhanced tool enables loading
experimental expression data into the network and simulating its dynamics under
various biological conditions or perturbations. As a proof of concept, we tested
two sets of published experimental data, one related to inflammatory bowel
disease condition and the other to breast cancer treatment. We predict some of
the major observations obtained following these laboratory experiments, and
provide new insights that may shed additional light on these results. Tool
requirements: Cytoscape 3.x, JAVA 8 Availability: The tool is freely available at
http://bionsi.wix.com/bionsi, where a complete user guide and a step-by-step
manual can also be found.
PMID- 29946423
TI - Is it time to scrap Scadding and adopt computed tomography for initial evaluation
of sarcoidosis?
AB - In this review, we argue for the use of high-resolution computed tomography
(HRCT) over chest X-ray in the initial evaluation of patients with sarcoidosis.
Chest X-ray, which has long been used to classify disease severity and offer
prognostication in sarcoidosis, has clear limitations compared with HRCT,
including wider interobserver variability, a looser association with lung
function, and poorer sensitivity to detect important lung manifestations of
sarcoidosis. In addition, HRCT offers a diagnostic advantage, as it better
depicts targets for biopsy, such as mediastinal/hilar lymphadenopathy and focal
parenchymal disease. Newer data suggest that specific HRCT findings may be
associated with important prognostic outcomes, such as increased mortality. As we
elaborate in this update, we strongly recommend the use of HRCT in the initial
evaluation of the patient with sarcoidosis.
PMID- 29946424
TI - Chronic pancreatitis: review and update of etiology, risk factors, and
management.
AB - Chronic pancreatitis is a syndrome involving inflammation, fibrosis, and loss of
acinar and islet cells which can manifest in unrelenting abdominal pain,
malnutrition, and exocrine and endocrine insufficiency. The Toxic-Metabolic,
Idiopathic, Genetic, Autoimmune, Recurrent and Severe Acute Pancreatitis,
Obstructive (TIGAR-O) classification system categorizes known causes and factors
that contribute to chronic pancreatitis. Although determining disease etiology
provides a framework for focused and specific treatments, chronic pancreatitis
remains a challenging condition to treat owing to the often refractory, centrally
mediated pain and the lack of consensus regarding when endoscopic therapy and
surgery are indicated. Further complications incurred include both exocrine and
endocrine pancreatic insufficiency, pseudocyst formation, bile duct obstruction,
and pancreatic cancer. Medical treatment of chronic pancreatitis involves
controlling pain, addressing malnutrition via the treatment of vitamin and
mineral deficiencies and recognizing the risk of osteoporosis, and administering
appropriate pancreatic enzyme supplementation and diabetic agents. Cornerstones
in treatment include the recognition of pancreatic exocrine insufficiency and
administration of pancreatic enzyme replacement therapy, support to cease smoking
and alcohol consumption, consultation with a dietitian, and a systematic follow
up to assure optimal treatment effect.
PMID- 29946425
TI - Recent advances in cancer outcomes in HIV-positive smokers.
AB - HIV-infected smokers are at relatively higher risk of cancer than HIV-infected
non-smokers. HIV weakens the immune system and renders infected individuals more
vulnerable to the carcinogenic effects of smoking. HIV-infected smokers suffer
more aggressive forms of cancers than do non-smokers because of the cumulative
effects of the virus and cigarette smoke carcinogens. The major types of cancer
observed in HIV-infected smokers are lung, head and neck, esophageal, anal, and
cervical cancers. In this review, we will discuss the recent advances in cancer
outcomes, primarily in terms of cancer incidence, prevalence, and progression in
HIV patients who are smokers.
PMID- 29946426
TI - Recent advances in understanding and managing non-alcoholic fatty liver disease.
AB - Non-alcoholic fatty liver disease is a leading cause of chronic liver disease
that can lead to cirrhosis, hepatocellular cancer, and end-stage liver disease,
and it is linked to elevated cardiovascular- and cancer-related morbidity and
mortality. Insulin resistance related to metabolic syndrome is the main
pathogenic trigger that, in association with adverse genetic, lifestyle, and
other factors, precipitates the development of non-alcoholic fatty liver disease.
Biochemical markers and radiological imaging, along with liver biopsy in selected
cases, help in the disease's diagnosis and prognostication. Weight loss is the
cornerstone treatment of non-alcoholic fatty liver disease; however, it is
difficult to achieve and maintain, so pharmacotherapy was developed. The
remarkable evolution in understanding disease pathogenesis has led to the
development of new medical therapies and even the modification of currently
available ones. This review summarizes recent advances in understanding the
epidemiology, natural history, pathogenesis, diagnosis, and management of non
alcoholic fatty liver disease.
PMID- 29946427
TI - New insights into the immunomodulatory properties of poxvirus cytokine decoy
receptors at the cell surface.
AB - Poxviruses encode a set of secreted proteins that bind cytokines and chemokines
as a strategy to modulate host defense mechanisms. These viral proteins mimic the
activity of host cytokine decoy receptors but have unique properties that may
enhance their activity. Here, we describe the ability of poxvirus cytokine
receptors to attach to the cell surface after secretion from infected cells, and
we discuss the advantages that this property may confer to these viral
immunomodulatory proteins.
PMID- 29946428
TI - Current understanding and management of Helicobacter pylori infection: an updated
appraisal.
AB - In addition to its role in gastric conditions, Helicobacter pylori has been found
to contribute to the development of several non-gastric issues in recent years.
Eradication therapy is the only effective management strategy to minimize the H.
pylori-related gastric cancer and extra-gastric complications. For an effective
"test and treat" strategy, diagnosis and therapy are both important. Because the
infection is usually asymptomatic, patient selection is a critical issue for
timely diagnosis and many clinical and demographic factors should be considered.
Clarithromycin and metronidazole resistance rates also need to be considered
while eradication therapy is offered. In this report, we discuss the issues which
must be taken into account for the correct and timely diagnosis and for the
antibiotic therapy-based management of H. pylori infection.
PMID- 29946429
TI - The evolving role of endoscopy in the diagnosis of premalignant gastric lesions.
AB - Gastric adenocarcinoma is a disease that is often detected late, at a stage when
curative treatment is unachievable. This must be addressed through changes in our
approach to the identification of patients at increased risk by improving the
detection and risk assessment of premalignant changes in the stomach, including
chronic atrophic gastritis and intestinal metaplasia. Current guidelines
recommend utilising random biopsies in a pathology-led approach in order to stage
the extent and severity of gastritis and intestinal metaplasia. This random
method is poorly reproducible and prone to sampling error and fails to
acknowledge recent advances in our understanding of the progression to gastric
cancer as a non-linear, branching evolutionary model. Data suggest that recent
advances in endoscopic imaging modalities, such as narrow band imaging, can
achieve a high degree of accuracy in the stomach for the diagnosis of these
premalignant changes. In this review, we outline recent data to support a
paradigm shift towards an endoscopy-led approach to diagnosis and staging of
premalignant changes in the stomach. High-quality endoscopic interrogation of the
chronically inflamed stomach mucosa, supported by targeted biopsies, will lead to
more accurate risk assessment, with reduced rates of under or missed diagnoses.
PMID- 29946431
TI - META-pipe Authorization service.
AB - We describe the design, implementation, and use of the META-pipe Authorization
service. META-pipe is a complete workflow for the analysis of marine metagenomics
data. We will provide META-pipe as a web based data analysis service for ELIXIR
users. We have integrated our Authorization service with the ELIXIR Authorization
and Authentication Infrastructure (AAI) that allows single sign-on to services
across the ELIXIR infrastructure. We use the Authorization service to authorize
access to data on the META-pipe storage system and jobs in the META-pipe job
queue. Our Authorization server was among the first services that integrated with
ELIXIR AAI. The code is open source at: https://gitlab.com/uit-sfb/AuthService2.
PMID- 29946430
TI - Recent advances in the management of lymphangioleiomyomatosis.
AB - Lymphangioleiomyomatosis is a rare disorder that predominantly affects women and
is characterized by progressive cystic changes in the lung, leading to gradually
worsening shortness of breath and lung function impairment. Pleural complications
such as pneumothorax and chylothorax commonly occur in these patients.
Lymphangioleiomyomatosis can occur as a form of lung involvement in tuberous
sclerosis complex or as a sporadic form (without tuberous sclerosis complex).
Etiology in both forms of this disease centers on mutations in the tuberous
sclerosis genes. Advances in our understanding of the regulatory role of tuberous
sclerosis gene products (hamartin/tuberin) in the mechanistic target of rapamycin
(mTOR) signaling pathway have led to the identification of effective therapy
(mTOR inhibitors) for a rare disorder, once considered uniformly fatal. Here, we
summarize the evolution of current concepts regarding lymphangioleiomyomatosis
with an emphasis on recent advances and unresolved issues.
PMID- 29946432
TI - Recent advances in the detection of repeat expansions with short-read next
generation sequencing.
AB - Short tandem repeats (STRs), also known as microsatellites, are commonly defined
as consisting of tandemly repeated nucleotide motifs of 2-6 base pairs in length.
STRs appear throughout the human genome, and about 239,000 are documented in the
Simple Repeats Track available from the UCSC (University of California, Santa
Cruz) genome browser. STRs vary in size, producing highly polymorphic markers
commonly used as genetic markers. A small fraction of STRs (about 30 loci) have
been associated with human disease whereby one or both alleles exceed an STR
specific threshold in size, leading to disease. Detection of repeat expansions is
currently performed with polymerase chain reaction-based assays or with Southern
blots for large expansions. The tests are expensive and time-consuming and are
not always conclusive, leading to lengthy diagnostic journeys for patients,
potentially including missed diagnoses. The advent of whole exome and whole
genome sequencing has identified the genetic cause of many genetic disorders;
however, analysis pipelines are focused primarily on the detection of short
nucleotide variations and short insertions and deletions (indels). Until
recently, repeat expansions, with the exception of the smallest expansion (SCA6),
were not detectable in next-generation short-read sequencing datasets and would
have been ignored in most analyses. In the last two years, four analysis methods
with accompanying software (ExpansionHunter, exSTRa, STRetch, and TREDPARSE) have
been released. Although a comprehensive comparative analysis of the performance
of these methods across all known repeat expansions is still lacking, it is clear
that these methods are a valuable addition to any existing analysis pipeline.
Here, we detail how to assess short-read data for evidence of expansions,
reviewing all four methods and outlining their strengths and weaknesses.
Implementation of these methods should lead to increased diagnostic yield of
repeat expansion disorders for known STR loci and has the potential to detect
novel repeat expansions.
PMID- 29938108
TI - A biochemical logarithmic sensor with broad dynamic range.
AB - Sensory perception often scales logarithmically with the input level. Similarly,
the output response of biochemical systems sometimes scales logarithmically with
the input signal that drives the system. How biochemical systems achieve
logarithmic sensing remains an open puzzle. This article shows how a biochemical
logarithmic sensor can be constructed from the most basic principles of chemical
reactions. Assuming that reactions follow the classic Michaelis-Menten kinetics
of mass action or the more generalized and commonly observed Hill equation
response, the summed output of several simple reactions with different
sensitivities to the input will often give an aggregate output response that
logarithmically transforms the input. The logarithmic response is robust to
stochastic fluctuations in parameter values. This model emphasizes the simplicity
and robustness by which aggregate chemical circuits composed of sloppy components
can achieve precise response characteristics. Both natural and synthetic designs
gain from the power of this aggregate approach.
PMID- 29938108
TI - A biochemical logarithmic sensor with broad dynamic range.
AB - Sensory perception often scales logarithmically with the input level. Similarly,
the output response of biochemical systems sometimes scales logarithmically with
the input signal that drives the system. How biochemical systems achieve
logarithmic sensing remains an open puzzle. This article shows how a biochemical
logarithmic sensor can be constructed from the most basic principles of chemical
reactions. Assuming that reactions follow the classic Michaelis-Menten kinetics
of mass action or the more generalized and commonly observed Hill equation
response, the summed output of several simple reactions with different
sensitivities to the input will often give an aggregate output response that
logarithmically transforms the input. The logarithmic response is robust to
stochastic fluctuations in parameter values. This model emphasizes the simplicity
and robustness by which aggregate chemical circuits composed of sloppy components
can achieve precise response characteristics. Both natural and synthetic designs
gain from the power of this aggregate approach.
PMID- 29946435
TI - Evaluation of defense strategy against Influenza A in cell line models.
AB - Background: Influenza virus can cause both seasonal infections and unpredictable
pandemics. Rapidly evolving avian H5N1 virus is getting increasingly infective
for humans. Since avian Influenza can be transmitted by domestic birds, serving
as a key link between wild aquatic birds and humans, an effective measure to
control the influenza transmission would be eradication of the infection in
poultry. It is known that the virus penetrates into the cell through binding with
the terminal oligosaccharides - sialic acids (SA) - on the cell surfaces. Removal
of SA might be a potential antiviral strategy. An approach to developing chicken
lines that are resistant to influenza viruses could be the creation of
genetically modified birds. Thus it is necessary to select a gene that provides
defense to influenza. Here we have expressed in cells a range of exogenous
sialidases and estimated their activity and specificity towards SA residues.
Methods: Several bacterial, viral and human sialidases were tested. We adopted
bacterial sialidases from Salmonella and Actinomyces for expression on the cell
surface by fusing catalytic domains with transmembrane domains. We also selected
Influenza A/PuertoRico/8/34/H1N1 neuraminidase and human membrane sialidase (
hNeu3) genes. Lectin binding assay was used for estimation of a alpha (2,3)
sialylation level by fluorescent microscopy and FACS. Results: We compared
sialidases from bacteria, Influenza virus and human. Sialidases from Salmonella
and Influenza A neuraminidase effectively cleaved alpha (2-3)-SA receptors. Viral
neuraminidase demonstrated a higher activity. Sialidases from Actinomyces and
hNeu3 did not show any activity against alpha (2-3) SA under physiological
conditions. Conclusion: Our results demonstrated that sialidases with different
specificity and activity can be selected as genes providing antiviral defence.
Combining chosen sialidases with different activity together with tissue-specific
promoters would provide an optimal level of desialilation to prevent infection.
Tissue specific expression of the sialidases could protect domestic birds from
infection.
PMID- 29946436
TI - Cross sectional study to determine chloroquine resistance among Plasmodium
falciparum clinical isolates from Khartoum, Sudan.
AB - Background: Malaria continues to present a global health threat; the World
Health Organization (WHO) reported 214 million cases of malaria by the year 2015
with a death rate of 438000. Sudan is endemic to malaria with over 95% of malaria
cases due to Plasmodium falciparum. Chloroquine is a well-established drug in the
treatment of P. falciparum malaria although its use has declined since its
introduction as the drug of choice in treatment of malaria in Sudan. The
mechanism of resistance has been attributed to mutations in P. falciparum
Chloroquine resistance transporter gene coding for a key food vacuole proteins.
In current study we aimed at verifying the genetic cause of resistance to
Chloroquine in field isolates of P. falciparum. Methods: Twenty P. falciparum
cases were diagnosed from East Nile hospital in Khartoum and recruited in the
investigation. Nested PCR was conducted to isolate mutation region in the PfCRT
gene and the amplicons were sequenced using Sanger sequencing technique
(Macrogen, Soule Korea). Results: 16/20 (80%) of the field isolates contained
base pair mutation of codon 76 in the pfcrt gene thus being resistant to
chloroquine treatment and only 4/20 (20%) did not contain such mutation.
Conclusions: High treatment failures associated with Chloroquine treatment is
evident of the high prevalence of mutant strains of P. falciparum field isolates
thus suggesting the reduced relevance of Chloroquine as a treatment choice in the
management of P. falciparum malaria.
PMID- 29946437
TI - Successful CRISPR/Cas9 mediated homologous recombination in a chicken cell line.
AB - Background: CRISPR/Cas9 system is becoming the dominant genome editing tool in a
variety of organisms. CRISPR/Cas9 mediated knock out has been demonstrated both
in chicken cell lines and in chicken germ cells that served to generate
genetically modified birds. However, there is limited data about CRISPR/Cas9
dependent homology directed repair (HDR) for avian, even in cell culture. Few
attempts have been made with integrations in safe harbor loci of chicken genome
that induces constitutive expression of the inserted gene. Gene expression under
an endogenous promoter would be more valuable than under a constitutive exogenous
promoter, as it allows the gene expression to be tissue-specific. Methods: Three
gRNAs were chosen to target chicken 3'-untranslated region of GAPDH gene. Cas9
mediated activity in the targeted locus for the gRNAs in DF-1 cells was estimated
by T7E1 assay. To edit the locus, the HDR cassette was added along with
CRISPR/Cas9. The inserted sequence contained eGFP in frame with a GAPDH coding
sequence via P2A and Neomycin resistance gene ( neoR) under cytomegalovirus
promoter. Correct integration of the cassette was confirmed with fluorescent
microscopy, PCR analysis and sequencing. Enrichment of modified cells was done by
G418 selection. Efficiency of integration was assessed with fluorescence
activated cell sorting (FACS). Results: We have established a CRISPR/Cas9 system
to target an endogenous locus and precisely insert a gene under endogenous
control. In our system, we used positive and negative selection to enrich
modified cells and remove cells with undesirable insertions. The efficiency of
CRISPR/Cas9-mediated HDR was increased up to 90% via G418 enrichment. We have
successfully inserted eGFP under control of the chicken GAPDH promoter.
Conclusions: The approach can be used further to insert genes of interest under
control of tissue-specific promoters in primordial germ cells in order to produce
genetically modified birds with useful for biotechnological purposes features.
PMID- 29946438
TI - Significance of intra-operative blood pressure data resolution: A retrospective,
observational study.
AB - Background: With evolving techniques for analysis of blood pressure (BP)
variability, the importance of sampling resolution for intra-operative BP still
remains to be examined. This study aims at comparing BP data with beat-by-beat
vs. 15 second resolution. Methods: This is a retrospective analysis of intra
arterial BP data obtained from cardiac surgical patients from the intra-operative
period. Data was collected from two sources for each patient, one with beat-by
beat frequency, other at a frequency of once every 15 seconds. The fraction of
time and area under the curve beyond systolic BP thresholds of 95 - 135 mmHg were
calculated using data from both sources, for each patient. These were compared
using Wilcoxon ranked sum test for paired samples using R-statistics version
3.4.3. Results: There was a statistically significant difference (P < 0.001)
between the parameters from the two sources. This was especially true for
parameters below and outside the thresholds. Only time fraction showed
significant difference above the 135 mmHg threshold. Conclusion: Our preliminary
analysis shows a definitive difference between BP descriptors, depending on
sampling resolution. But the impact of this difference on the outcome predicting
models of the parameters stands to be ascertained. Future larger studies, powered
to examine the impact of sampling resolution on outcome predictive ability of BP
descriptors, with special emphasis on dynamic markers of complexity are
warranted.
PMID- 29946439
TI - Blood-derived extracellular vesicle proteins as potential biomarkers for the
diagnosis of early ER+ breast cancer and detection of lymph node involvement.
AB - Extracellular vesicles (EV's) are membrane surrounded structures released by
different cell types and are emerging as potential therapeutic and diagnostic
targets in cancer. In the present study, plasma samples derived from 7 patients
with metastatic and non-metastatic ER+ (estrogen receptor positive) breast cancer
(BC) were collected and their respective (EVs) isolated and the protein content
analyzed by mass spectrometry and FunRich analysis. Here we report on the
presence of two putative plasma EV biomarkers (which were absent in healthy
controls samples) that could be used to detect early ER+ breast cancer and for
those with lymph node (LN) involvement However, given the preliminar nature of
the work, further investigation in a larger patient cohort is warranted to
corroborate these findings. If confirmed, these biomarkers could be incorporated
into simple blood test kit for the early detection of those with ER+ breast
cancer and lymph node involvement.
PMID- 29946440
TI - segment_liftover : a Python tool to convert segments between genome assemblies.
AB - The process of assembling a species' reference genome may be performed in a
number of iterations, with subsequent genome assemblies differing in the
coordinates of mapped elements. The conversion of genome coordinates between
different assemblies is required for many integrative and comparative studies.
While currently a number of bioinformatics tools are available to accomplish this
task, most of them are tailored towards the conversion of single genome
coordinates. When converting the boundary positions of segments spanning larger
genome regions, segments may be mapped into smaller sub-segments if the original
segment's continuity is disrupted in the target assembly. Such a conversion may
lead to a relevant degree of data loss in some circumstances such as copy number
variation (CNV) analysis, where the quantitative representation of a genomic
region takes precedence over base-specific accuracy. segment_liftover aims at
continuity-preserving remapping of genome segments between assemblies and
provides features such as approximate locus conversion, automated batch
processing and comprehensive logging to facilitate processing of datasets
containing large numbers of structural genome variation data.
PMID- 29946441
TI - Adolescent girls' attitudes toward female genital mutilation: a study in seven
African countries.
AB - Background: The study's aim is to examine adolescent girls' attitudes toward the
continuation or discontinuation of female genital mutilation (FGM) in association
with their demographics in seven different countries in Africa. Methods: Data
from the women's survey of the Demographic and Health Surveys (DHS) conducted by
the respective ministries (of Health and Family Welfare) in Egypt, Guinea, Kenya,
Mali, Niger, Senegal and Sierra Leone were used. Adolescent girls (15-19 years)
were included in the current analysis: Egypt (N=636), Guinea (N=1994), Kenya (N=
1767), Mali (N=2791), Niger (N=1835), Senegal (N=3604), Sierra Leone (N=1237).
Results: Prevalence of supporting the continuation of FGM among adolescent girls
was in Egypt 58%, Guinea 63%, Kenya 16%, Mali 72%, Niger 3%, Senegal 23%, and
Sierra Leone 52%. Being Muslim and having low economic status were significantly
associated with supporting the continuation of FGM in five of the participating
countries. Girls having no education or only primary education in Guinea, Kenya,
Mali and Sierra Leone exhibited a higher likelihood of supporting FGM than girls
with secondary or higher education. In Egypt, Niger and Senegal there was no
association between education and supporting FGM. The girls who stated that they
had no exposure to media showed the higher likelihood of supporting FGM in
Guinea, Kenya, and Senegal than those with exposure to media. Conclusions: The
current study argues that increasing media coverage and education, and reducing
poverty are of importance for shifting adolescent girls' attitudes in favor of
discontinuation of FGM.
PMID- 29946442
TI - Automation of ReactomeFIViz via CyREST API.
AB - Pathway- and network-based approaches project seemingly unrelated genes onto the
context of pathways and networks, enhancing the analysis power that cannot be
achieved via gene-based approaches. Pathway and network approaches are routinely
applied in large-scale data analysis for cancer and other complicated diseases.
ReactomeFIViz is a Cytoscape app, providing features for researchers to perform
pathway- and network-based data analysis and visualization by leveraging manually
curated Reactome pathways and highly reliable Reactome functional interaction
network. To facilitate adoption of this app in bioinformatics software pipeline
and workflow development, we develop a CyREST API for ReactomeFIViz by exposing
some major features in the app. We describe a use case to demonstrate the use of
this API in a Python-based notebook, and believe the new API will provide the
community a convenient and powerful tool to perform pathway- and network-based
data analysis and visualization using our app in an automatic way.
PMID- 29946443
TI - Comparing protein structures with RINspector automation in Cytoscape.
AB - Residue interaction networks (RINs) have been shown to be relevant
representations of the tertiary or quaternary structures of proteins, in
particular thanks to network centrality analyses. We recently developed the
RINspector Cytoscape app, which couples centrality analyses with backbone
flexibility predictions. This combined approach permits the identification of
crucial residues for the folding or function of the protein that can constitute
good targets for mutagenesis experiments. Here we present an application
programming interface (API) for RINspector that enables interplay between
Cytoscape, RINspector and external languages, such as R or Python. This API
provides easy access to batch centrality calculations and flexibility
predictions, and allows for the easy comparison of results between different
structures. These comparisons can lead to the identification of specific and
conserved central residues, and show the impact of mutations to these and other
residues on the flexibility of the proteins. We give two use cases to demonstrate
the interest of these functionalities and provide the corresponding scripts: the
first concerns NMR conformers, the second focuses on mutations in a structure.
PMID- 29946444
TI - A method for transplantation of human HSCs into zebrafish, to replace humanised
murine transplantation models.
AB - Haematopoietic stem cell (HSC) transplantation is a critical therapy for
haematopoietic malignancies and immune disorders. Incomplete or delayed
engraftment of HSCs in the host results in increased risk of infection and
morbidity. The mechanisms of HSC engraftment are poorly understood and
understanding these processes will increase transplantation success on many
levels. Current animal models are immunocompromised 'humanised' mice transplanted
with human HSCs. Harmful procedures include genetic manipulations and irradiation
to ablate the mouse immune system, and opaque mouse tissues make visualisation of
the early steps of HSC engraftment impossible. There is a need for new models to
offer alternatives to humanised mice in the study of HSC transplantation. Here we
described a detailed method for transplantation of human HSCs into zebrafish,
before the onset of adaptive immunity. Human HSCs were purified from whole blood
by enrichment of the CD34 cell population using a positive magnetic selection and
further purified using an anti-CD34 antibody and cell sorting. Sorted CD34 cells
were transplanted into the blood stream of 52 hour old zebrafish larvae. Human
HSCs home into the zebrafish haematopoietic niche, where they engage with
endothelial cells and undergo cell division. Our model offers the opportunities
to image in vivo human HSC engraftment in a transparent organism, without the
myeloablative strategies used in mice, and provides a unique system to understand
the dynamic process of engraftment and replace current murine models. This
technique can be applied to current engraftment protocols to validate the
viability and efficiency of cryofrozen HSC grafts. This humanised zebrafish model
will be instrumental to develop the 3Rs values in stem cell transplantation
research and our detailed protocol will increase the chances of uptake of this
zebrafish model by the mouse community.
PMID- 29946445
TI - The use of PrP transgenic Drosophila to replace and reduce vertebrate hosts in
the bioassay of mammalian prion infectivity.
AB - Prion diseases are fatal neurodegenerative conditions of humans and vertebrate
species. The transmissible prion agent is a novel infectious particle composed
principally of PrP Sc, an abnormal isomer of the normal host protein PrP C. The
only reliable method to detect mammalian prion infectivity is by bioassay,
invariably in a vertebrate host. The current prion bioassays typically involve
intracerebral or peripheral inoculation of test material into the experimental
host and subsequent euthanasia when clinical signs of terminal prion disease
become evident. It may be months or years before the onset of clinical disease
becomes evident and a pre-determined clinical end-point is reached. Consequently,
bioassay of prion infectivity in vertebrate species is cumbersome, time
consuming, expensive, and increasingly open to ethical debate because these
animals are subjected to terminal neurodegenerative disease. Prions are a
significant risk to public health through the potential for zoonotic transmission
of animal prion diseases. Attention has focussed on the measurement of prion
infectivity in different tissues and blood from prion-infected individuals in
order to determine the distribution of infectious prions in diseased hosts. New
animal models are required in order to replace or reduce, where possible, the
dependency on the use of vertebrate species, including the 'gold standard' mouse
prion bioassay, to assess prion infectivity levels. Here we highlight the
development of a Drosophila-based prion bioassay, a highly sensitive and rapid
invertebrate animal system that can efficiently detect mammalian prions. This
novel invertebrate model system will be of considerable interest to biologists
who perform prion bioassays as it will promote reduction and replacement in the
number of sentient animals currently used for this purpose. This article is a
composite of previous methods that provides an overview of the methodology of the
model and discusses the experimental data to promote its viability for use
instead of more sentient hosts.
PMID- 29946446
TI - TMD symptoms and vertical mandibular symmetry in young adult orthodontic patients
in North Sumatra, Indonesia: a cross-sectional study.
AB - Background: Temporomandibular joint disorder (TMD) includes symptoms of pain and
dysfunction in the muscles of mastication and the temporomandibular joint.
Differences in vertical condylar height, observed in the assessment of mandibular
asymmetry, is a structural alteration that represents a risk factor for TMD. The
study aimed to evaluate the association between TMD symptoms and vertical
mandibular symmetry in young adult orthodontic patients in North Sumatra,
Indonesia. Methods: The cross-sectional study included 18-25-year-old (mean +/-
SD, 21.9 +/- 2.0 years) old orthodontic patients admitted to the Dental Hospital
of Universitas Sumatera Utara, Medan, between June 2016 and March 2017. Vertical
mandibular asymmetry was assessed from all 106 subjects using Kjellberg's
technique from pre-treatment panoramic radiographs. The TMD symptoms were
assessed by structural interviews using modified questionnaires based on
Temporomandibular Disorder Diagnostic Index and Fonseca's Anamnestic Index.
Results: Of the 106 subjects, 26 (24.5% of the total) with vertical mandibular
symmetry and 39 (36.8%) with vertical mandibular asymmetry were positive for TMD
symptoms. By contrast, 17 patients (16.0% of the total) with vertical condylar
symmetry and 24 patients (22.6%) with vertical mandibular asymmetry were regarded
negative for TMD symptoms. There was no significant difference (p=0.520) in TMD
symptoms based on vertical mandibular symmetry. Conclusion: The results from this
studied Sumatran population indicate that there are common TMD symptoms in young
adult orthodontic patients, but there is no significant association between
vertical mandibular asymmetry and TMD symptoms. Further study on the development
of TMD, mandibular asymmetry and treatment planning for growing patients is
suggested, using longitudinal and transitional approaches.
PMID- 29946447
TI - Clinical agreement in the American Society of Anesthesiologists physical status
classification.
AB - Background: The American Society of Anesthesiologists physical status (ASA-PS)
classification is not intended to predict risk, but increasing ASA-PS class has
been associated with increased perioperative mortality. The ASA-PS class is being
used by many institutions to identify patients that may require further workup or
exams preoperatively. Studies regarding the ASA-PS classification system show
significant variability in class assignment by anesthesiologists as well as
providers of different specialties when provided with short clinical scenarios.
Discrepancies in the ASA-PS accuracy have the potential to lead to unnecessary
testing and cancelation of surgical procedures. Our study aimed to determine
whether these differences in ASA-PS classification were present when actual
patients were evaluated rather than previously published scenario-based studies.
Methods: A retrospective chart review was completed for patients >/= 65 years of
age undergoing elective total hip or total knee replacements. One hundred seventy
seven records were reviewed of which 101 records had the necessary data. The
outcome measures noted were the ASA-PS classification assigned by the internal
medicine clinic provider, the ASA-PS classification assigned by the Pre
Anesthesia Unit (PAU) clinic provider, and the ASA-PS classification assigned on
the day of surgery (DOS) by the anesthesia provider conducting the anesthetic
care. Results: A statistically significant difference was shown between the
internal medicine and the PAU preoperative ASA-PS designation as well as between
the internal medicine and DOS designation (McNemar p = 0.034 and p = 0.025). Low
kappa values were obtained confirming the inter-observer variation in the
application of the ASA-PS classification of patients by providers of different
specialties [Kappa of 0.170 (- 0.001, 0.340) and 0.156 (- 0.015, 0.327)].
Conclusions: There was disagreement in the ASA-PS class designation between two
providers of different specialties when evaluating the same patients with access
to full medical records. When the anesthesia-run PAU and the anesthesia assigned
DOS ASA-PS class designations were evaluated, there was agreement. This agreement
was seen between anesthesia providers regardless of education or training level.
The difference in the application of the ASA-PS classification in our study
appeared to be reflective of department membership and not reflective of the
individual provider's level of training.
PMID- 29946449
TI - Comparing appropriateness of antibiotics for nursing home residents by setting of
prescription initiation: a cross-sectional analysis.
AB - Background: The pervasive, often inappropriate, use of antibiotics in healthcare
settings has been identified as a major public health threat due to the resultant
widespread emergence of antibiotic resistant bacteria. In nursing homes (NH), as
many as two-thirds of residents receive antibiotics each year and up to 75% of
these are estimated to be inappropriate. The objective of this study was to
characterize antibiotic therapy for NH residents and compare appropriateness
based on setting of prescription initiation. Methods: This was a retrospective,
cross-sectional multi-center study that occurred in five NHs in southern
Wisconsin between January 2013 and September 2014. All NH residents with an
antibiotic prescribing events for suspected lower respiratory tract infections
(LRTI), skin and soft tissue infections (SSTI), and urinary tract infections
(UTI), initiated in-facility, from an emergency department (ED), or an outpatient
clinic were included in this sample. We assessed appropriateness of antibiotic
prescribing using the Loeb criteria based on documentation available in the NH
medical record or transfer documents. We compared appropriateness by setting and
infection type using the Chi-square test and estimated associations of
demographic and clinical variables with inappropriate antibiotic prescribing
using logistic regression. Results: Among 735 antibiotic starts, 640 (87.1%) were
initiated in the NH as opposed to 61 (8.3%) in the outpatient clinic and 34
(4.6%) in the ED. Inappropriate antibiotic prescribing for urinary tract
infections differed significantly by setting: NHs (55.9%), ED (73.3%), and
outpatient clinic (80.8%), P = .023. Regardless of infection type, patients who
had an antibiotic initiated in an outpatient clinic had 2.98 (95% CI: 1.64-5.44,
P < .001) times increased odds of inappropriate use. Conclusions: Antibiotics
initiated out-of-facility for NH residents constitute a small but not trivial
percent of all prescriptions and inappropriate use was high in these settings.
Further research is needed to characterize antibiotic prescribing patterns for
patients managed in these settings as this likely represents an important, yet
under recognized, area of consideration in attempts to improve antibiotic
stewardship in NHs.
PMID- 29946448
TI - The prevalence, antibiotic resistance and mecA characterization of coagulase
negative staphylococci recovered from non-healthcare settings in London, UK.
AB - Background: Coagulase negative staphylococci (CoNS) are important reservoirs of
antibiotic resistance genes and associated mobile genetic elements and are
believed to contribute to the emergence of successful methicillin resistant
Staphylococcus aureus (MRSA) clones. Although, these bacteria have been linked to
various ecological niches, little is known about the dissemination and genetic
diversity of antibiotic resistant CoNS in general public settings. Methods: Four
hundred seventy-nine samples were collected from different non-healthcare/general
public settings in various locations (n = 355) and from the hands of volunteers
(n = 124) in London UK between April 2013 and Nov 2014. Results: Six hundred
forty-three staphylococcal isolates belonging to 19 staphylococcal species were
identified. Five hundred seventy-two (94%) isolates were resistant to at least
one antibiotic, and only 34 isolates were fully susceptible. Sixty-eight (11%)
mecA positive staphylococcal isolates were determined in this study. SCCmec types
were fully determined for forty-six isolates. Thirteen staphylococci (19%)
carried SCCmec V, followed by 8 isolates carrying SCCmec type I (2%), 5 SCCmec
type IV (7%), 4 SCCmec type II (6%), 1 SCCmec type III (2%), 1 SCCmec type VI
(2%), and 1 SCCmec type VIII (2%). In addition, three isolates harboured a new
SCCmec type 1A, which carried combination of class A mec complex and ccr type
1.MLST typing revealed that all S. epidermidis strains possess new MLST types and
were assigned the following new sequence types: ST599, ST600, ST600, ST600,
ST601, ST602, ST602, ST603, ST604, ST605, ST606, ST607 and ST608. Conclusions:
The prevalence of antibiotic resistant staphylococci in general public settings
demonstrates that antibiotics in the natural environments contribute to the
selection of antibiotic resistant microorganisms. The finding of various SCCmec
types in non-healthcare associated environments indicates the complexity of
SCCmec. We also report on new MLST types that were assigned for all S.
epidermidis isolates, which demonstrates the genetic variability of these
isolates.
PMID- 29946450
TI - Risk factors for poor outcome in community-onset Clostridium difficile infection.
AB - Background: A substantial portion of Clostridium difficile infection (CDI) cases
occur in communities, and community-onset CDI (CO-CDI) can lead to serious
complications including mortality. This study aimed to identify the risk factors
for a poor outcome in CO-CDI. Methods: We performed a retrospective review of all
inpatients with CDI, in a 1300-bed tertiary-care hospital in Korea, from 2008
through 2015. CO-CDI was defined as CDI occurring within 48 h of admission. Poor
outcome was defined as follows: 1) all-cause 30-day mortality, 2) in-hospital
mortality, or 3) surgery due to CDI. Results: Of a total 1256 CDIs occurring over
8 years, 152 (12.1%) cases were classified as CO-CDI and 23 (15.1%) had a poor
outcome, including 22 (14.5%) cases of mortality and 2 (1.3%) cases of surgery.
Patients with a poor outcome had a higher mean age than those without a poor
outcome (75.8 vs. 69.6 years, p = 0.03). The proportion of men and prior proton
pump inhibitor (PPI) use were significantly higher in the poor outcome group
(65.2% vs. 41.9%, p = 0.04; 39.1% vs. 17.6%, p = 0.02, respectively).
Multivariate binary logistic model showed that PPI use and anemia (hemoglobin <
10 g/dL) at presentation were significantly associated with a poor outcome
(adjusted odds ratio [aOR], 3.76; 95% confidence interval [95CI], 1.26-11.21,
aOR, 4.67; 95CI, 1.52-14.34, respectively). Conclusions: Clinicians should not
only be aware of the possibility of CDI in the community setting but also pay
more attention to PPI-using elderly patients with anemia in consideration of a
poor outcome.
PMID- 29946451
TI - Characteristics of the antibiotic regimen that affect antimicrobial resistance in
urinary pathogens.
AB - Background: Treatment duration, treatment interval, formulation and type of
antimicrobial (antibiotic) are modifiable factors that will influence
antimicrobial selection pressure. Currently, the impact of the route of
administration on the occurrence of resistance in humans is unclear. Methods: In
this retrospective multi-center cohort study, we assessed the impact of different
variables on antimicrobial resistance (AMR) in pathogens isolated from the
urinary tract in older adults. A generalized estimating equations (GEE) model was
constructed using 7397 Escherichia coli (E. coli) isolates. Results: Resistance
in E. coli was higher when more antibiotics had been prescribed before isolation
of the sample, especially in women (significant interaction p = 0.0016) and up to
nine preceding prescriptions it was lower for higher proportions of preceding
parenteral prescriptions (significant interactions p = 0.0067). The laboratory
identity, dying, and the time between prescription and sampling were important
confounders (p < 0.001). Conclusions: Our model describing shows a dose-response
relation between antibiotic use and AMR in E. coli isolated from urine samples of
older adults, and, for the first time, that higher proportions of preceding
parenteral prescriptions are significantly associated with lower probabilities of
AMR, provided that the number of preceding prescriptions is not extremely high
(>=10 during the 1.5 year observation period; 93% of 5650 included patients).
Trial registration: Retrospectively registered.
PMID- 29946452
TI - Mid-term absorbable monofilament is safe and effective for gastrointestinal
anastomosis - PROMEGAT - A single-arm prospective observational study.
AB - Introduction: Various suture materials and suture techniques are used to perform
gastrointestinal anastomosis after tumour resection, but the best combination is
still a matter of debate. Methods: This multi-centre, international, single-arm,
prospective observational study aimed at demonstrating the non-inferiority of a
mid-term absorbable monofilament in comparison to braided sutures in
gastrointestinal anastomosis. Monosyn suture was used to create the
gastrointestinal anastomosis and the frequency of anastomotic leakage until day
of discharge was chosen as the primary parameter. The outcome was compared to the
results published for braided sutures in the literature. Secondary parameters
were the time to perform the anastomosis, length of hospital stay, costs, and
postoperative complications. Results: The anastomosis leakage rate was 2.91%,
indicating that Monosyn suture was not inferior to braided sutures used in
gastrointestinal anastomosis. Of the reported anastomotic suture techniques, the
single layer continuous method was the fastest and most economical technique in
the present observational study. Conclusion: Monosyn suture is safe and effective
in gastrointestinal anastomosis and represents a good alternative to other
sutures used for gastrointestinal anastomosis. With regard to safety, time and
cost-efficiency, the single-layer continuous technique should be considered a
preferred method. The transfer of results from clinical studies into daily
practice with regard to surgical techniques for gastrointestinal anastomosis
should be further evaluated in larger studies or in nationwide registries.
PMID- 29946453
TI - Laparoscopic common bile duct exploration; a preferential pathway for elderly
patients.
AB - Background: Laparoscopic common bile duct exploration (LCBDE) has emerged as a
recommended alternative to endoscopic retrograde cholangiopancreatography (ERCP)
for the management of choledocholithiasis. However, its use in the elderly has
been limited, and evidence of its safety and efficacy in these patients is yet to
be established. This study describes our experience of LCBDE in elderly patients,
analysing the safety and efficacy of this technique in comparison to younger
patients. Methods: All patients undergoing laparoscopic cholecystectomy (LC) with
LCBDE for choledocholithiasis in our unit between January 2015 and January 2017
were included. Data pertaining to patient demographics, comorbidities,
investigations, operative technique and outcomes were analysed. Patients were
divided into 2 groups based on age (Group A:<65 years vs Group B: >/ = 65 years)
for comparative analysis. Results: 124 patients (Group A: 65, Group B: 59) were
included. Group B were more co-morbid and had a higher ASA grade than Group A.
However, there was no significant difference between groups in rates of
conversion to open or complications, including bile leak (3.1% vs 5.1%, p =
0.67), retained stone (4.6% vs 1.7%, p = 0.62), or complications according to
Clavien-Dindo classification (p = 0.78). Re-intervention rates were also similar
between groups (7.7% vs 3.4%, p = 0.44 and 3.1% vs 3.4%, p = 1.0 respectively),
as was length of stay. Conclusion: Despite higher frequency of comorbidities and
ASA grade, LCBDE in elderly patients is safe and effective, and has similar
outcomes to younger patients. Therefore elderly patients with choledocholithiasis
should be offered LCBDE as an alternative to ERCP.
PMID- 29946454
TI - Cardiac Hydatid cysts; presentation and management. A case series.
AB - Introduction: Hydatid cyst commonly affects liver and lung. Cardiac Hydatid cyst
is an extremely rare disease. The aim of this study is to report the presentation
and management of cardiac Hydatid diseases admitted to two major cardiac centers.
Method: A retrospective, case series study, conducted in two centers during two
years. Each case presented separately regarding presentation, diagnosis and
management. Results: Four cases have been reported, age ranged from 14 to 42
years with mean age of 24.75 years. Three patients (75%) were male, one patient
(25%) was female. Three cases (75%) had history of chest pain, 2 cases (50%) had
palpitation, and one case (25%) had nausea, vomiting and fever. Echocardiography
was the initial diagnostic test in 2 cases (50%), final diagnostic test in two
cases (50%). In 3 cases (75%) the cyst was found in the left ventricle and one
case (25%) in right ventricle. Median sternotomy was performed for all cases.
Conclusion: Cardiac Hydatid cyst is a very rare disease. Chest pain is the most
common symptom. Surgery is the main modality of treatment.
PMID- 29946455
TI - Stresses generated by two zygomatic implant placement techniques associated with
conventional inclined anterior implants.
AB - Purpose: To make a comparative evaluation, by means of the finite element method,
of the stress generated on supporting tissues and prosthetic system components,
using zygomatic implants with the exteriorized and extramaxillary techniques, and
different placement positions, associated either with inclined anterior implants,
or those without inclination. Materials and methods: Eight (8) tridimensional
models were created to represent the clinical situations being researched, using
the dataset of scanned images of an edentulous model. The implants and prosthetic
components were photographed on millimeter paper and inserted into Rhinoceros 3D
modeling computer software. From the measurements made on the image, the virtual
models were made. The application force was distributed on the occlusal surface
of the working side of the left maxillary first molar, first and second
premolars, and incisal regions of the central incisor, simulating the occlusal
load during mastication, in a total of 150 N. Results: The extramaxillary
technique presented considerable variation in increased tension on the prosthesis
screws and bone tissue. In the exteriorized technique, the highest tension values
occurred in the region of the ridge, and the lowest, on the zygomatic process;
the absence of cantilever reduced the stress on bone tissue in almost all
regions. Conclusion: The exteriorized technique was shown to be more favorable to
the distribution of stresses on the micro-unit screws and bone tissue, with the
model with zygomatic implant placed in the region of the first molar and inclined
anterior implant presenting the best results.
PMID- 29946457
TI - Hypocalcemia after thyroidectomy: iPTH levels and iPTH decline are predictive?
Retrospective cohort study.
AB - Background: Hypocalcemia is the most common complication of thyroid surgery. The
aim of this study was to determine the early predictive factors of postoperative
hypocalcemia and to analyze their efficiency. Methods: We performed a
retrospective study of 345 consecutive patients who underwent total thyroidectomy
at the Endocrine Surgery Department (Policlinico G. Rodolico Hospital of Catania)
between January 2011 and November 2013. We measured serum intact parathormone
(iPTH) levels preoperatively and 4 h after surgery. The threshold values of
hypocalcemia for iPTH levels and iPTH relative decline were obtained by receiver
operating curves (ROC) analysis. Results: The incidence of hypocalcemia was 32.2%
(111 of 345 patients). Our statistical analysis revealed that hypocalcemia rate
was strongly correlated with the lower iPTH values and greater iPTH decline (P <
0.001). The threshold enabling prediction of hypocalcemia were 12,5 pg/mL for
iPTH and 55,7% for relative iPTH decline. Patients with iPTH <12,5 pg/mL
developed hypocalcemia in 58.6% of cases while those with iPTH >=12,5 pg/dl in
18.8%. Among 175 patients with iPTH relative decline greater than 55,7%
hypocalcemia was diagnosed in 91 cases (52%), while other 170 patients with iPTH
relative decline less than 55,7% developed hypocalcemia only in 20 cases (11,7%).
Conclusions: The decreased iPTH levels and increased iPTH relative decline
resulted to be an accurate predictive factors of postoperative hypocalcemia. The
early administration of Calcium and vitamin D in the high-risk patients should be
put on in order to prevent the symptoms of hypocalcemia and to reduce the costs
and duration of hospitalization.
PMID- 29946456
TI - Mesh repair of paraumblical hernia, outcome of 58 cases.
AB - Background: According to the literature, defects in para-umbilical hernias up to
2 cm in diameter could be sutured primarily. For defects larger than 2 cm in
dimeters, mesh repair is recommended. The aim of this study is to evaluate the
outcome of para-umbilical hernia repair with proline mesh regardless of its size.
Methods: In this retrospective study, patients with para-umbilical hernia, who
were managed by onlay mesh placement were presented, and followed for 1-6 years.
Several variables were studied including patients' socio-demographic data, post
operative complications, morbidity and mortality. Results: The series includes 58
patients, the age ranged from 18 to 85 years with median age of 44 years and
inter-quartile range of 13.5 years. Mean body mass index was (30.9 +/- 4.2). From
49 female patients; 43 (87.8%) were multipara. Forty seven cases (81%) presented
for the first time, and 11 cases (19%) had recurrent hernias. Twenty patients
(34.5%) had hernia defect <=2 cm, while 38 patients (65.5%) had hernia size >2
cm. Superficial surgical site infection was found in 6 patients (10.34%). Seroma
was found in one female patient (1.72%). One patient (1.72%) had recurrent hernia
after 19 months. Conclusion: Mesh onlay repair by open surgery can be applied to
all sizes of para umbilical hernias, it has low recurrence rate and the rates of
morbidity and recurrence are comparable with international standard.
PMID- 29946458
TI - Primary small cell carcinoma of the larynx. Survival time of 47 months. Case
report.
AB - Small cell carcinoma (SCC) of the larynx is a rare type of neuroendocrine
carcinoma (NEC), few cases of which have been described in the literature. The
prognosis for this type of carcinoma is poor, with a survival time typically not
exceeding two years. We describe the case of a 54-year-old male patient with a
primary tumor in the right ventricular band and a biopsy compatible with SCC. The
patient underwent radiotherapy (RT) and concomitant chemotherapy (QT) and, after
a relapse at 17 months, underwent total laryngectomy with bilateral neck
dissection. The survival time was 47 months. Further studies are required to
elucidate the possible causes of the better prognosis in some cases.
PMID- 29946459
TI - Gene expression of CCL8 and CXCL10 in peripheral blood leukocytes during early
pregnancy in cows.
AB - Background: The aim of the present study was to evaluate CCL8 and CXCL10
expression and its regulatory mechanism in peripheral blood leukocytes (PBLs) at
the time of maternal recognition in cows. Blood samples were collected on 14, 15,
16, 17 and 18 d after artificial insemination (AI). Based on the day of return of
estrus, cows were divided into three groups, pregnant (n = 5), early embryonic
mortality (EEM; n = 5) and late embryonic mortality (LEM; n = 5). The gene
expression levels in PBLs were assessed with quantitative real-time reverse
transcription PCR. Results: The expression of CCL8 and CXCL10 mRNA in PBLs
gradually increased from 14 to 18 d of pregnant cows and significant differences
were observed on 18 d (P < 0.05), whereas no significant changes were observed
both in EEM and LEM cows. Interferon-stimulated protein 15 kDa (ISG15), myxovirus
resistance gene (MX) 1 and MX2 mRNA expression in PBLs increased from 14 to 18 d
which was significant on 18 d of pregnant cows as well as in LEM cows (P < 0.05),
but no changes were observed in EEM cows. To determine whether the expression of
CCL8 and CXCL10 in PBLs was regulated by pregnancy-related substances or not,
expression level was assessed after exposure to interferon-tau (IFNT) and CCL16.
Monocytes, granulocytes and lymphocytes were obtained using density-gradient
centrifugation and flow cytometry. The addition of IFNT (100 ng/mL) and CCL16
(100 ng/mL) to cultured PBLs increased the expression of CCL8 and CXCL10 mRNA (P
< 0.05). The expression of ISG15, MX1 and MX2 mRNA in PBLs was also stimulated by
IFNT and CCL16 (P < 0.05). Conclusions: The expression of CCL8 and CXCL10 genes
increased in PBLs during early pregnancy. Since IFNT stimulated CCL8 and CXCL10
expression in cultured PBLs, the increase of CCL8 and CXCL10 might be pregnancy
dependent events. The expression of both CCL8 and CXCL10 in PBLs was stimulated
by CCL16 as well as IFNT, suggesting a chemokine interaction that at least
includes CCL8, CXCL10 and CCL16, and may play a role in regulating maternal
recognition in cows.
PMID- 29946460
TI - Lipopolysaccharide immune stimulation but not beta-mannanase supplementation
affects maintenance energy requirements in young weaned pigs.
AB - Background: Pathogen or diet-induced immune activation can partition energy and
nutrients away from growth, but clear relationships between immune responses and
the direction and magnitude of energy partitioning responses have yet to be
elucidated. The objectives were to determine how beta-mannanase supplementation
and lipopolysaccharide (LPS) immune stimulation affect maintenance energy
requirements (MEm) and to characterize immune parameters, digestibility, growth
performance, and energy balance. Methods: In a randomized complete block design,
30 young weaned pigs were assigned to either the control treatment (CON; basal
corn, soybean meal and soybean hulls diet), the enzyme treatment (ENZ; basal diet
+ 0.056% beta-mannanase), or the immune system stimulation treatment (ISS; basal
diet + 0.056% beta-mannanase, challenged with repeated increasing doses of
Escherichia coli LPS). The experiment consisted of a 10-d adaptation period, 5-d
digestibility and nitrogen balance measurement, 22 h of heat production (HP)
measurements, and 12 h of fasting HP measurements in indirect calorimetry
chambers. The immune challenge consisted of 4 injections of either LPS (ISS) or
sterile saline (CON and ENZ), one every 48 h beginning on d 10. Blood was
collected pre- and post-challenge for complete blood counts with differential,
haptoglobin and mannan binding lectin, 12 cytokines, and glucose and insulin
concentrations. Results: Beta-mannanase supplementation did not affect immune
status, nutrient digestibility, growth performance, energy balance, or MEm. The
ISS treatment induced fever, elevated proinflammatory cytokines and decreased
leukocyte concentrations (P < 0.05). The ISS treatment did not impact nitrogen
balance or nutrient digestibility (P > 0.10), but increased total HP (21%) and
MEm (23%), resulting in decreased lipid deposition (-30%) and average daily gain
(-18%) (P < 0.05). Conclusions: This experiment provides novel data on beta
mannanase supplementation effects on immune parameters and energy balance in pigs
and is the first to directly relate decreased ADG to increased MEm independent of
changes in feed intake in immune challenged pigs. Immune stimulation increased
energy partitioning to the immune system by 23% which limited lipid deposition
and weight gain. Understanding energy and nutrient partitioning in immune
stressed pigs may provide insight into more effective feeding and management
strategies.
PMID- 29946461
TI - miR-25 modulates triacylglycerol and lipid accumulation in goat mammary
epithelial cells by repressing PGC-1beta.
AB - Background: The goat (Caprahircus) is one of the most important livestock
animals. Goat milk fat is an important component in the nutritional quality of
goat milk. Growing evidence points to the critical roles of microRNAs (miRNAs) in
lipid metabolism. Results: Using a highly sensitive method of S-poly(T) plus for
miRNAs detection, we analyze the expression patterns of 715 miRNAs in goat
mammary gland tissues at different stages of lactation. We observed that miR-25
expression had an inverse relationship with milk production. Overexpression of
miR-25 significantly repressed triacylglycerol synthesis and lipid droplet
accumulation. To explore the regulatory mechanism of miR-25 in milk lipid
metabolism, we analyzed its putative target genes with bioinformatics analysis
followed by 3'-UTR assays. Peroxisome proliferative activated receptor gamma
coactivator 1 beta (PGC-1beta), a key regulator of lipogenics was identified as a
direct target of miR-25 with three specific sites within its 3'-UTR. In addition,
miR-25 mimics in goat mammary epithelial cells reduced the expressions of genes
involved in lipid metabolism. Conclusions: Taken together, our results show miR
25 is potentially involved in lipid metabolism and we reveal the function of the
miR-25/PGC-1beta regulatory axis during lactation.
PMID- 29946462
TI - Use of health promotion manga to encourage physical activity and healthy eating
in Japanese patients with metabolic syndrome: a case study.
AB - Background: The present case study investigated the feasibility of using manga
(Japanese-style comic books) to promote physical activity and healthy eating
behavior in Japanese patients with metabolic syndrome. Methods: A one-arm pre
post intervention was conducted in a Japanese suburban community. Twenty
participants with a diagnosis of metabolic syndrome were recruited via health
checkups. Health promotion manga were developed by the researcher, a publishing
specialist, and a professional illustrator. We measured participants' self
reported physical activity, eating behavior, and psychological readiness to
change toward engaging in healthy behavior. Results: At 1 month after the
intervention there were no significant differences in physical activity scores,
but small positive changes in vigorous (R2 = 0.02) and moderate (R2 = 0.01)
physical activity scores were observed. Total healthy eating behavior scores were
significantly improved (p < 0.05, R2 = 0.47). In addition, participants reported
positive change in psychological readiness, such as increased intention to engage
in healthy behavior, enhanced self-efficacy, and benefits of using manga.
Conclusions: This study demonstrates that manga interventions have potential to
encourage healthy eating in patients with metabolic syndrome.
PMID- 29946463
TI - Effect of pirfenidone on wound healing in lung transplant patients.
AB - Background: The drug pirfenidone has been shown to slow the progression and
decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is
unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor
beta, a known contributor to wound healing. We evaluated whether patients taking
pirfenidone until lung transplantation had increased risk of impaired wound
healing post-transplant. This information could determine whether pirfenidone
should be discontinued prior to listing to allow for a wash-out period. Methods:
We retrospectively reviewed patients who underwent lung transplantation for
pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January
2014 to December 2015. Results: We describe 18 patients who took pirfenidone up
to a month before transplant. Aside from one patient who experienced sternal
dehiscence due to a surgical issue, all remaining patients did well with no
evidence of airway dehiscence. Each of these 17 patients had been on pirfenidone
for at least 30 days; nine patients had been on pirfenidone for over 90 days.
Baseline characteristics including age, sex, body mass index, renal function,
liver function, glucose level, pre-transplant corticosteroid use, and post
transplant immunosuppressant therapy were similar. Conclusions: In our
experience, pirfenidone may be safely continued until lung transplantation. Only
one patient in our series experienced impaired wound healing related to a
surgical issue, even when pirfenidone was continued until lung transplantation.
We found no evidence of impaired wound healing or airway complications after lung
transplantation in patients who were treated with pirfenidone before lung
transplantation.
PMID- 29946464
TI - Fluticasone furoate/Vilanterol 92/22 MUg once-a-day vs Beclomethasone
dipropionate/Formoterol 100/6 MUg b.I.D.: a 12-month comparison of outcomes in
mild-to-moderate asthma.
AB - Background: Bronchial asthma is an inflammatory disease of the airways.
Beclomethasone dipropionate/Formoterol (BDP/F) and Fluticasone furoate/Vilanterol
(FF/V) are two of the most effective LABA/ICS combinations for managing
persistent bronchial asthma. Aim of the study was to compare the outcomes
achieved in mild-to-moderate asthma patients assuming BDP/F 100/6 MUg b.i.d.
(Group A) or FF/V 92/22 MUg once-daily (Group B) for 12-months. No head-to-head
long-term comparison is available at present. Methods: Data were automatically
and anonymously obtained from the institutional database: FEV1% predicted values;
the exacerbation and hospitalization rates; days of hospitalization; GP and/or
specialist visits; days of inactivity; courses of systemic steroids and/or
antibiotics were recorded at baseline and after 3, 6 and 12 months of both
treatments. The overall adherence to treatments was also calculated. The
propensity score method was used for matching and comparing the two cohorts of
patients; Anova and Wilcoxon tests were used for checking the trends and time-to
time comparisons over the period; statistical significance was accepted for p <
0.05. Results: The PS-matching process returned a cohort of 40 group A patients
matched with 40 patients of group B, fully comparable for demographics, clinical
characteristics, and comorbidities. The improvement in lung function was
significant in both groups (p < 0.001), even if it was significantly higher and
time-dependent in group B. The mean (+/-SE) exacerbation rate/patient changed
from 0.63 (+/-0.13) at baseline to 0.53 (+/-0.12) after three; to 0.58 (+/-0.13)
after six, and to 0.60 (+/-0.18) after twelve months in group A (p = ns), while
from of 1.05 (+/-0.16) at baseline, to 0.28 (+/-0.07) after three; to 0.33 (+/
0.08) after six, and to 0.18 (+/-0.08) after twelve months in group B (p <
0.001), respectively. The mean hospitalization rate/patient changed from 0.25 +/-
0.07 at baseline to 0.15 (+/-0.06) after three; to 0.08 (+/-0.04) after six, and
to 0.13 (+/-0.05) after twelve months in group A (p = ns), while from 0.30 (+/
0.07) at baseline to 0.08 (+/-0.04) after three; to 0.10 (+/-0.05) after six, and
to 0.03 (+/-0.03) after twelve months in group B (p < 0.001), respectively. Also
mean duration of hospitalization and days of inactivity were in favour of FF/V
treatment over time (in both cases p < 0.001). GP's visits were reduced by both
treatments (p < 0.007 in group A and p < 0.001 in group B, respectively, while
Specialist's visits only dropped during FF/V (p < 0.001). Steroid and antibiotic
courses were significantly reduced by both treatments, even if more
systematically in group B (p < 0.001 vs p < 0.007, and p < 0.001 vs p < 0.044,
respectively). Moreover, changes in all outcomes considered proved time-dependent
during the FF/V treatment only, particularly over the second semester. Finally,
the overtime adherence to treatment was higher by 22 days during FF/V .
Conclusions: Both the ICS/LABA combinations proved effective, even if
characterized by different patterns of effectiveness either in terms of lung
function and of long-term clinical outcomes. Only the once-daily inhalation of
combined FF/V 92/22 MUg once-daily optimized systematically the exacerbation and
hospitalization rates in mild-to-moderate asthma, together with all other
outcomes over time. The effectiveness of FF/V 92/22 once-daily MUg proved
progressive and time-dependent over the twelve-month period of the study, and
associated to a higher adherence to treatment.
PMID- 29946465
TI - "Pulmonary Actinomycosis attributable to Actinomyces meyeri presenting as cardiac
tamponade: a case report".
AB - Background: Recently, it is reported that Actinomyces meyeri is the most common
species causing actinomycosis. However, to our knowledge, there was no report
about pulmonary actinomycosis attributable to A. meyeri presenting as cardiac
tamponade. Case presentation: Hereby we describe a case of pulmonary
actinomycosis attributable to A. meyeri presenting as cardiac tamponade. At
first, the patient was diagnosed with bacterial pericarditis with lung abscess in
the left lower lung lobe and underwent pericardial drainage. Three days after the
removal of the drainage tube, atrial fibrillation followed by cardiac arrest with
asystole occurred and immediate cardiopulmonary resuscitation restored his
circulation. Thereafter, he underwent pneumocentesis of the lung abscess and the
culture grew A. meyeri. He was successfully treated with penicillin G.
Conclusion: This is the first case of pulmonary actinomycosis attributable to A.
meyeri presenting as cardiac tamponade. We believe that an increased awareness of
the disease is necessary to expedite diagnosis therefore minimizing morbidity and
mortality.
PMID- 29946466
TI - Assessing the factor structure and measurement invariance of the eating attitude
test (EAT-26) across language and BMI in young Arab women.
AB - Background: The objective of the study was to determine the factorial structure
and test the measurement invariance of the EAT-26 in a large probability sample
of young female university students in Qatar (n = 2692), a Muslim country in the
Middle East. Methods: The maximum number of factors was derived based on results
from initial exploratory factor analysis (EFA) in the first-half of the randomly
split sample (Sample 1). A subsequent EFA and Exploratory Structural Equation
Models (ESEM) were conducted to identify the number of valid factors. A five
factor model with 19 items was identified as the optimal factor structure. This
structure was further replicated using ESEM in the second-half of the sample
(Sample 2). Multi-group Confirmatory Factor Analyses (CFAs) were conducted at
this stage and their fit was evaluated with and without further sub-grouping by
language (Arabic and English) and BMI (underweight, normal weight, and
overweight/obese). Finally, measurement invariance tests were conducted in the
entire sample assessing equivalence across language and BMI within the final five
factor model. Results: The five-factor structure of the new EAT-19 [fear of
getting fat (FGF), eating-related control (ERC), food preoccupation (FP),
vomiting-purging behavior (VPB), and social pressure to gain weight (SP)]
provided the best fit: CFI = 0.976, TLI = 0.952, RMSEA = 0.045 (90%CI 0.039
0.051), SRMR = 0.018, CD =1.000. CFAs supported metric invariance for language
and for BMI. Language and BMI-based population heterogeneity comparisons provided
modest and small-to-moderate evidence for differential factor means,
respectively. Conclusion: Although the five-factor model of the EAT-19
demonstrated good item characteristics and reliability in this young female
population, the lack of scalar invariance across language and BMI-categories pose
measurement challenges for use of this scale for screening purposes. Future
studies should develop culture- and BMI-specific cut-offs when using the EAT as a
screening instrument for disordered eating in non-clinical populations.
PMID- 29946467
TI - Serum levels of VEGF and MCSF in HER2+ / HER2- breast cancer patients with
metronomic neoadjuvant chemotherapy.
AB - Metronomic therapy has been gaining importance in the neoadjuvant setting of
breast cancer treatment. Its clinical benefits may involve antiangiogenic
machinery. Cancer cells induce angiogenesis to support tumor growth by secreting
factors, such as vascular endothelial growth factor (VEGF). In breast cancer,
Trastuzumab (TZM) based treatment is of key importance and is believed to reduce
diameter and volume of blood vessels as well as vascular permeability. Here in we
investigated serum levels of angiogenic factors VEGF and MCSF in patients
receiving metronomic neoadjuvant therapy with or without TZM. We observed in
HER2+ cohort stable levels of MCSF through treatment, whereas VEGF trend was of
decreasing levels. In HER2- cohort we observed increasing levels of MCSF and VEGF
trend. Overall, HER2+ patients had better pathological response to treatment.
These findings suggest that angiogenic pathway may be involved in TZM anti
tumoral effect in the neoadjuvant setting.
PMID- 29946468
TI - Chemerin is elevated in multiple myeloma patients and is expressed by stromal
cells and pre-adipocytes.
AB - Chemerin is a recently discovered adipokine shown to be involved in both
inflammatory and metabolic processes. Here, we demonstrate that chemerin serum
levels are elevated in patients with multiple myeloma and that it increases with
disease progression. We found that chemerin is expressed by stromal cells and
preadipocytes, whereas its receptor CCRL2 is expressed by primary myeloma cells,
suggesting a paracrine signaling loop between bone marrow stromal
cells/adipocytes and myeloma cells. This is the first study exploring chemerin
and its receptors in multiple myeloma.
PMID- 29946469
TI - Kinomic profiling of glioblastoma cells reveals PLCG1 as a target in restricted
glucose.
AB - Background: For glioblastoma (GBM) treatments to be effective in vivo,
understanding the effects of the tumor microenvironment is imperative. In
traditional cell culture conditions, glucose concentrations do not model
physiologic levels, nor the diminished concentrations found in tumor niches. We
therefore sought to profile the differences in kinase activity in GBM cells
cultured in restricted glucose to identify pathways that could be targeted with
small molecule inhibitors. Methods: Using the PamStation12 platform, we examined
the ability of GBM lysates from cells cultured in standard or low glucose
conditions to phosphorylate 144 tyrosine and 144 serine/threonine peptides that
correspond to known protein phosphorylation sites. Potential kinase targets were
identified and validated using small molecule kinase inhibitors in GBM spheroid
cultures. Results: Using results from two GBM patient-derived xenografts, we
determined common changes to peptides derived from Phospholipase C, Gamma 1
(PLCG1) and Raf-1. Using PLC and Raf inhibitors, we found a significantly
stronger growth inhibitory effect of the PLC inhibitor U73122 under restricted
glucose conditions. In contrast, Raf inhibitors were significantly growth
inhibitory regardless of the nutrient level tested. Conclusions: Together, our
data demonstrate that kinase activity is altered in low glucose conditions and
that kinomic profiling can assist with the identification of effective strategies
to target GBM growth. Our data further suggest the importance of accurately
modeling the tumor microenvironment to reproduce cancer cell signaling and
develop drug screens for anti-cancer agents.
PMID- 29946470
TI - The involvement of the nuclear lamina in human and rodent spermiogenesis: a
systematic review.
AB - The nuclear lamina (NL) is a filamentous protein meshwork, composed essentially
of lamins, situated between the inner nuclear membrane and the chromatin. The NL
is a component of the nuclear envelope, interacts with a wide range of proteins
and is required for normal nuclear structure and physiological development.
During spermiogenesis the spermatid nucleus is elongated, and dramatically
reduced in size with protamines replacing histones to produce a highly compacted
chromatin. There is mounting evidence from studies in human and rodent, that the
NL plays an important role in mammalian spermatid differentiation during
spermiogenesis. In this review, we summarize and discuss the data available in
the literature regarding the involvement of lamins and their direct or indirect
partners in normal and abnormal human spermiogenesis.
PMID- 29946472
TI - Relationship between gait kinematics and walking energy expenditure during
pregnancy in South African women.
AB - Background: Various musculoskeletal changes occurring during pregnancy may lead
to the change in gait and contribute to the increase in walking energy
expenditure. Previous research indicates that changes in gait mechanics may lead
to the increase in mechanical work required during walking. However, there is
little information to indicate if changes in gait mechanics during pregnancy have
impact on active or total energy expenditure. Therefore, the primary aim of this
study was to investigate the relationship between changes in gait kinematics and
walking energy expenditure in pregnant women. Methods: Thirty-five women (mean
age = 27.5 +/- 6.1 years) volunteered for the study during various stages of
pregnancy (1st trimester average = 12.1 +/- 2.2 weeks; 2nd trimester = 22.3 +/-
2.6 weeks; 3rd trimester = 31.4 +/- 2.6 weeks). 3D motion analysis was used to
assess changes in kinematic parameters during walking at self-selected pace.
Resting metabolic rate, and walking energy expenditure expressed in terms of rate
and cost of O2 were analysed with portable metabolic analyser. Results: Only
medio-lateral deviation of centre of gravity (COGML) increased 13.6% between the
1st and 2nd, and 39.3% between 2nd and 3rd trimester (p <= 0.001). However, self
selected walking speed depicted strong significant positive linear relationship
with net O2 rate (r = 0.70; p <= 0.001), and was strongly associated with the
vertical excursion of the COG (r = 0.75, p <= 0.001). Conclusions: Changes in
gait mechanics during pregnancy may lead to an increase in walking energy
expenditure. However, the consequent increase in walking energy cost may not be
sufficient to offset the natural energy sparing mechanism.
PMID- 29946471
TI - Experimental folate deficiency in human subjects: what is the influence of
vitamin C status on time taken to develop megaloblastic anaemia?
AB - Background: In 1962 Victor Herbert developed megaloblastic anaemia four months
after commencing a severely folate-deficient diet whereas, in his self-experiment
50 years later, this author took 19 months to fully deplete his liver folate
store. This author proposed that his own larger initial liver folate store, due
to his vegetarian diet and consumption of fortified foods, was the cause of the
time difference. Main text: This author now proposes that Herbert was also likely
to have been deficient in vitamin C, thus shortening the time taken to develop
folate deficiency. Several human experiments have confirmed the role of vitamin C
in protecting reduced forms of folate from oxidation. Although there has
historically been no consensus on the required intake of vitamin C, and official
recommendations set a level below that required to ensure plasma saturation,
recent research supports an intake that would ensure saturation. There have been
no longitudinal experiments on human subjects since the introduction of voluntary
or mandatory folic acid fortification of food, and the few published models
differ significantly in their estimates of human liver folate storage capacity.
Conclusion: Because of the importance of folate in one-carbon metabolism, the
potential influence of vitamin C intake on the time taken to deplete the liver
folate store should be experimentally investigated.
PMID- 29946473
TI - Effects of heat stress and dehydration on cognitive function in elite female
field hockey players.
AB - Background: It has previously been suggested that heat exposure and hypohydration
have negative effects on cognitive performance, which may impact upon sporting
performance. The aim of the present study was to examine the independent effects
of heat stress and hypohydration on cognitive performance in elite female field
hockey players. Methods: Eight unacclimatised elite field hockey players (age: 22
+/- 3 y; height: 1.68 +/- 0.05 m; body mass: 63.1 +/- 6.0 kg) completed a
cognitive test battery before and after 50 min of field hockey specific exercise
on a treadmill in four experimental trials; two in hot conditions (33.3 +/- 0.1
degrees C), and two in moderate (16.0 +/- 3.0 degrees C), both with and without
ad libitum water intake. Results: On the visual search test, participants were
faster overall in the heat (1941 vs. 2104 ms, p = 0.001). Response times were
quicker in the heat on the Sternberg paradigm (463 vs. 473 ms, p = 0.024) and
accuracy was improved (by 1.9%, p = 0.004). There was no effect of hydration
status on any of the markers of cognitive function. Conclusions: Overall, the
findings suggest that in elite field hockey players exposure to heat enhances
response times and/or accuracy on a battery of cognitive function tests. However,
hypohydration does not appear to affect cognitive performance in elite field
hockey players.
PMID- 29946474
TI - Signals of gastroesophageal reflux disease caused by incretin-based drugs: a
disproportionality analysis using the Japanese adverse drug event report
database.
AB - Background: Incretin-based drugs are important in the treatment of type 2
diabetes. However, among the incretin-based drugs, glucagon-like peptide-1
receptor agonists (GLP-1-RAs) have been reported to cause gastroesophageal reflux
disease (GERD)-like symptoms making it difficult to continue treatment.
Therefore, with the aim of clarifying the relationship between incretin-based
drugs and GERD-like symptoms, we conducted a pharmacoepidemiological study using
the Japanese adverse drug event report database (JADER). Methods: Dipeptidyl
peptidase-4 inhibitors (DPP-4-Is) and GLP-1-RAs were set as the incretin-based
target drugs. The reporting odds ratio (ROR) and the information component (IC)
was used for the detection of quantitative signals. Furthermore, we also compared
the time to onset of GERD-like symptoms by log-rank test. Results: GERD-like
symptoms were reported in 36 GLP-1-RAs cases (ROR: 5.61, 95% confidence interval
(95% CI): 3.95-7.96 and IC: 2.17, 95% CI: 1.66-2.67) and GLP-1-RAs were detected
in the signal. In contrast, DPP-4-Is were not detected in the signal.There was no
sex difference with regard to the expression time of GERD-like symptoms by GLP-1
RAs (log-rank test, p = 0.5381). However, the expression time of GERD-like
symptoms from GLP-1-RAs was shorter in patients older than 70 years of age than
that in those younger than 70 years of age (log-rank test, p < 0.0001).
Conclusions: The administration of GLP-1-RA had a higher incidence of GERD-like
symptoms earlier than the administration of DPP-4-Is. In this study, although we
think that further investigation is necessary, and suggest that patients older
than 70 years of age who have been administered GLP-1-RAs need earlier attention
to address GERD-like symptoms than younger patients.
PMID- 29946475
TI - Dietary manipulation: a sustainable way to mitigate methane emissions from
ruminants.
AB - Methane emission from the enteric fermentation of ruminant livestock is a main
source of greenhouse gas (GHG) emission and a major concern for global warming.
Methane emission is also associated with dietary energy lose; hence, reduce feed
efficiency. Due to the negative environmental impacts, methane mitigation has
come forward in last few decades. To date numerous efforts were made in order to
reduce methane emission from ruminants. No table mitigation approaches are rumen
manipulation, alteration of rumen fermentation, modification of rumen microbial
biodiversity by different means and rarely by animal manipulations. However, a
comprehensive exploration for a sustainable methane mitigation approach is still
lacking. Dietary modification is directly linked to changes in the rumen
fermentation pattern and types of end products. Studies showed that changing
fermentation pattern is one of the most effective ways of methane abatement.
Desirable dietary changes provide two fold benefits i.e. improve production and
reduce GHG emissions. Therefore, the aim of this review is to discuss biology of
methane emission from ruminants and its mitigation through dietary manipulation.
PMID- 29946476
TI - Effects of an odor or taste stimulus applied to an artificial teat on the
suckling behavior of newborn dairy calves.
AB - Background: In their first days of life, dairy calves in artificial rearing
systems often have difficulty using an artificial teat for feeding. Methods: We
examined the age at which calves are able to stand up voluntarily and suckle as
well as their suckling behavior when presented with a plain dry teat versus a dry
teat modified with a presumably attractive odor or taste substance. Single-housed
newborn dairy calves (n = 51) were presented for ten consecutive days with a two
minute two-choice test, in which suckling time was recorded for 1) a plain
(control) teat versus a glucose-coated teat (taste test) and 2) a plain teat
versus a teat with a "Freshly Cut Grass" odor (odor test). Results: On average,
the calves were able to stand up voluntarily and suckle from the second or third
day of age on. The "Freshly Cut Grass" odor had no significant effect on their
suckling behavior. In contrast, the calves showed a significant preference for
suckling the glucose-coated teat and displayed a significantly longer total
suckling time in the taste test compared to the odor test. There were no
significant differences between sexes regarding suckling behavior. Conclusion:
The results of the present study show that glucose had a significant effect on
the calves' teat preference and significantly increased total suckling time with
a dry artificial teat. As such, glucose may increase suckling motivation in non
efficient drinkers or ill calves with low motivation to suckle.
PMID- 29946477
TI - The ACUTE (Ambulance CPAP: Use, Treatment effect and economics) feasibility
study: a pilot randomised controlled trial of prehospital CPAP for acute
respiratory failure.
AB - Background: Acute respiratory failure (ARF) is a common and life-threatening
medical emergency. Standard prehospital management involves controlled oxygen
therapy and disease-specific ancillary treatments. Continuous positive airway
pressure (CPAP) is a potentially beneficial alternative treatment that could be
delivered by emergency medical services. However, it is uncertain whether this
treatment could work effectively in United Kingdom National Health Service (NHS)
ambulance services and if it represents value for money. Methods: An individual
patient randomised controlled external pilot trial will be conducted comparing
prehospital CPAP to standard oxygen therapy for ARF. Adults presenting to
ambulance service clinicians will be eligible if they have respiratory distress
with peripheral oxygen saturation below British Thoracic Society (BTS) target
levels, despite titrated supplemental oxygen. Enrolled patients will be allocated
(1:1 simple randomisation) to prehospital CPAP (O_two system) or standard oxygen
therapy using identical sealed boxes. Feasibility outcomes will include incidence
of recruited eligible patients, number of erroneously recruited patients and
proportion of cases adhering to allocation schedule and treatment, followed up at
30 days and with complete data collection. Effectiveness outcomes will comprise
survival at 30 days (definitive trial primary end point), endotracheal
intubation, admission to critical care, length of hospital stay, visual analogue
scale (VAS) dyspnoea score, EQ-5D-5L and health care resource use at 30 days. The
cost-effectiveness of CPAP, and of conducting a definitive trial, will be
evaluated by updating an existing economic model. The trial aims to recruit 120
patients over 12 months from four regional ambulance hubs within the West
Midlands Ambulance Service (WMAS). This sample size will allow estimation of
feasibility outcomes with a precision of < 5%. Feasibility and effectiveness
outcomes will be reported descriptively for the whole trial population, and each
trial arm, together with their 95% confidence intervals. Discussion: This study
will determine if it is feasible, acceptable and cost-effective to undertake a
full-scale trial comparing CPAP and standard oxygen treatment, delivered by
ambulance service clinicians for ARF. This will inform NHS practice and prevent
inappropriate prehospital CPAP adoption on the basis of limited evidence and at a
potentially substantial cost. Trial registration: ISRCTN12048261. Registered on
30 August 2017. http://www.isrctn.com/ISRCTN12048261.
PMID- 29946478
TI - Adapting a perinatal empathic training method from South Africa to Germany.
AB - Background: Maternal mental health conditions are prevalent across the world. For
women, the perinatal period is associated with increased rates of depression and
anxiety. At the same time, there is widespread documentation of disrespectful
care for women by maternity health staff. Improving the empathic engagement
skills of maternity healthcare workers may enable them to respond to the mental
health needs of their clients more effectively. In South Africa, a participatory
empathic training method, the "Secret History" has been used as part of a
national Department of Health training program with maternity staff and has
showed promising results. For this paper, we aimed to describe an adaptation of
the Secret History empathic training method from the South African to the German
setting and to evaluate the adapted training. Methods: The pilot study occurred
in an academic medical center in Germany. A focus group (n = 8) was used to adapt
the training by describing the local context and changing the materials to be
relevant to Germany. After adapting the materials, the pilot training was
conducted with a mixed group of professionals (n = 15), many of whom were
trainers themselves. A pre-post survey assessed the participants' empathy levels
and attitudes towards the training method. Results: In adapting the materials,
the focus group discussion generated several experiences that were considered to
be typical interpersonal and structural challenges facing healthcare workers in
maternal care in Germany. These experiences were crafted into case scenarios that
then formed the basis of the activities used in the Secret History empathic
training pilot. Evaluation of the pilot training showed that although the
participants had high levels of empathy in the pre-phase (100% estimated their
empathic ability as high or very high), 69% became more aware of their own
emotional experiences with patients and the need for self-care after the
training. A majority, or 85%, indicated that the training was relevant to their
work as clinicians and trainers, that it reflected the German situation, and that
it may be useful ultimately to address emotional distress in mothers in the
perinatal phase. Conclusions: Our study suggests that it is possible to adapt an
empathic training method developed in a South African setting and apply it to a
German setting, and that it is well received by participants who may be involved
in healthcare worker training. More research is needed to assess adaptations with
other groups of healthcare workers in different settings and to assess empathic
skill outcomes for participants and women in the perinatal period.
PMID- 29946479
TI - DIAMOND (DIgital Alcohol Management ON Demand): a feasibility RCT and embedded
process evaluation of a digital health intervention to reduce hazardous and
harmful alcohol use recruiting in hospital emergency departments and online.
AB - Background: The harmful use of alcohol is a causal factor in more than 200
disease and injury conditions and leads to over 3 million deaths every year
worldwide. Relatively few problem alcohol users access treatment due to stigma
and lack of services. Alcohol-specific digital health interventions (DHI) may
help them, but trial data comparing DHI with face-to-face treatment are lacking.
Methods: We conducted a feasibility RCT of an alcohol DHI, testing recruitment,
online data-collection and randomisation processes, with an embedded process
evaluation. Recruitment ran from October 2015 for 12 months. Participants were
adults, drinking at hazardous and harmful levels, recruited from hospital
emergency departments (ED) in London or recruited online. Participants were
randomised to HeLP-Alcohol, a six module DHI with weekly reminder prompts (phone,
email or text message), or to face-to-face treatment as usual (TAU). Participants
were invited to take part in qualitative interviews after the trial. Results: The
trial website was accessed 1074 times: 420 people completed online eligibility
questionnaires; 350 did not meet eligibility criteria, 51 declined to
participate, and 19 were recruited and randomised. Follow-up data were collected
from three participants (retention 3/19), and four agreed to be interviewed for
the process evaluation. The main themes of the interviews were:Participants were
not at equipoise. They wanted to try the website and were disappointed to be
randomised to face-to-face, so they were less engaged and dropped out.Other
reasons for drop out included not accepting that they had a drink problem;
problem drinking interfering with their ability to take part in a trial or
forgetting appointments; having a busy life and being randomised to TAU made it
difficult to attend appointments. Conclusions: This feasibility RCT aimed to test
recruitment, randomisation, retention, and data collection methods, but recruited
only 19 participants. This illustrates the importance of undertaking feasibility
studies prior to fully powered RCTs. From the qualitative interviews we found
that potential recruits were not at equipoise for recruitment. An alternative
methodology, for example a preference RCT recruiting from multiple locations,
needs to be explored in future trials. Trial registration: International Standard
Randomized Controlled Trial Number: ISRCTN31789096.
PMID- 29946480
TI - Prospective evaluation of intimate partner violence in fracture clinics (PRAISE
2): protocol for a multicentre pilot prospective cohort study.
AB - Background: One third of women experience intimate partner violence (IPV) in
their lifetime. Orthopaedic health care professionals are in a good position to
identify women experiencing escalating physical violence and act to promote their
immediate safety, connect them to IPV resources, and reduce the risk of further
harm. However, there have been no studies that explore whether experiencing a
musculoskeletal injury can trigger or worsen IPV, and there have been no studies
on how experiences of IPV affect orthopaedic outcomes. The primary objective of
the PRAISE-2 pilot study is to assess the feasibility of conducting a large
cohort study to determine the association between IPV and injury-related
complications. The secondary clinical objectives are to preliminarily explore how
a history of IPV affects orthopaedic outcomes and how patterns of IPV change over
time following an orthopaedic injury. Methods: We will complete a pilot
multicentre prospective cohort study of 250 women with musculoskeletal injuries
to determine the feasibility of a multinational prospective cohort study that
will determine if prior or ongoing IPV affects orthopaedic outcomes following an
injury, and how patterns of IPV change over time. Our primary outcome is
feasibility measured using recruitment rate (success criterion 50 patients/site
in 12 months), adherence to visit windows (success criterion 75%), participant
retention (success criterion 85%), and data completeness (success criterion 80%).
Our secondary exploratory clinical outcomes are injury-related complications,
return to function, new IPV disclosures, utilization and cost of support
services, changes in abuse patterns, quality of life, and readiness to make
relationship changes. We will assess feasibility based on pre-defined criteria
for feasibility success and we will analyze secondary outcomes in an exploratory
fashion. Discussion: The PRAISE-2 pilot study is the first step toward
determining how experiences of IPV affect orthopaedic outcomes such as injury
related complications. This study will determine feasibility and assist in the
development of large-scale multinational prospective IPV studies for our future
IPV research program. This study will engage health care professionals from
around the world to increase awareness of how IPV affects patients'
musculoskeletal and injury outcomes. Trial registration: clinicaltrials.gov
NCT02529267. Registered 20 Aug 2015.
PMID- 29946481
TI - Rare Clinical Entity: Metastatic malignant struma ovarii diagnosed during
pregnancy - Lessons for management.
AB - Background: Malignant struma ovarii is an ovarian teratoma containing at least
50% thyroid tissue which has the potential to metastasize and produce thyroid
hormone. Given its rarity, management strategies are not well-established. We
report a case of metastatic malignant struma ovarii discovered during pregnancy
with lessons for evaluation and management. Case presentation: A 30-year-old
woman who was two months pregnant was discovered to have struma ovarii with over
half of the struma comprised of papillary thyroid cancer. Following tumor
resection, delivery, and thyroidectomy, she underwent evaluation with stimulated
thyroglobulin testing and diagnostic staging sodium iodide-131 scan (I-131),
which revealed the presence of skeletal metastases. Following administration of
320 mCi I-131, post-therapy scan also showed miliary pulmonary metastases with
improved ability to localize the bony and pulmonary metastases with concurrent
SPECT/CT imaging. A second dosimetry-guided I-131 therapy resulted in complete
resolution of pulmonary metastases; however, small foci of residual bone disease
persisted. Post-therapy scans demonstrated additional findings not shown on
diagnostic I-131 scans obtained prior to both her initial and second I-131
therapy. Conclusions: SPECT/CT provides accurate anatomic correlation and
localization of metastatic foci and can serve as a baseline study to assess
interval response to treatment. Post-therapy scans should always be obtained when
I-131 treatment is administered, as additional findings may be revealed versus
low dose I-131 activity diagnostic scans. This patient had a high metastatic
burden that would not have been discovered in a timely fashion with the
conservative approach advocated by others. Thyroidectomy followed by a diagnostic
staging radioiodine scan and a stimulated thyroglobulin level should be
considered in patients with malignant struma ovarii for guiding therapeutic I-131
administration as metastatic risk is difficult to predict based on
histopathologic examination.
PMID- 29946482
TI - Weight loss and bone mineral density in obese adults: a longitudinal analysis of
the influence of very low energy diets.
AB - Background: The long-term effect of weight reduction on skeletal health is not
well understood. The purpose of this study was to examine the impact of an
intensive medical weight loss intervention using very low energy diet (VLED) (~
800 cal/day) that result in significant changes in body weight, on total body
bone mineral density (BMD) over 2 years. Methods: We examined the impact of VLED
induced weight loss on BMD and FFM (Fat-free Mass) after 3-6 months and again
while in weight maintenance at 2 years in 49 subjects. The effects of absolute
and relative rate of weight reduction assessed by change in weight in kilograms
were assessed using general linear modeling, with baseline BMD (or FFM) as a
covariate, and age, sex and changes in body weight as primary model predictors.
Results: At the end of 2 years, the average weight loss was greater for men
(weight: 23.51 +/- 12.5 kg) than women (weight: 16.8 +/- 19.2 kg) and BMD loss
was greater among women (0.03 +/- 0.04 g/cm2 vs 0.01 +/- 0.04 g/cm2) (all p <
0.05). After adjusting for baseline BMD, age, and sex, there was a small but
significant association between total weight loss and 2-year BMD (beta = - 0.001
g/cm2; p = 0.01). Similarly, there was a significant independent association
between total weight loss and 2-year FFM (beta = - 116.5 g; p < 0.01).
Conclusions: Despite significant weight loss with VLED, there was only a small
loss is BMD.
PMID- 29946483
TI - Multiple massive domestication and recent amplification of Kolobok superfamily
transposons in the clawed frog Xenopus.
AB - Background: DNA transposons are generally destroyed by mutations and have short
lifespans in hosts, as they are neutral or harmful to the host and therefore not
conserved by natural selection. The clawed frog Xenopus harbors many DNA
transposons and certain families, such as T2-MITE, have extremely long lives.
These have ancient origins, but have shown recent transposition activity. In
addition, certain transposase genes may have been "domesticated" by Xenopus and
conserved over long time periods by natural selection. The aim of this study was
to elucidate the evolutionary interactions between the host and the long-lived
DNA transposon family it contains. Here, we investigated the molecular evolution
of the Kolobok DNA transposon superfamily. Kolobok is thought to contribute to T2
MITE transposition. Results: In the diploid western clawed frog Xenopus
tropicalis and the allotetraploid African clawed frog Xenopus laevis, we searched
for transposase genes homologous to those in the Kolobok superfamily. To
determine the amplification and domestication of these genes, we used molecular
phylogenetics and analyses of copy numbers, conserved motifs, orthologous gene
synteny, and coding sequence divergence between the orthologs of X. laevis and X.
tropicalis, or between those of two distant X. tropicalis lineages. Among 38 X.
tropicalis and 24 X. laevis prospective transposase genes, 10 or more in X.
tropicalis and 14 or more in X. laevis were apparently domesticated. These genes
may have undergone multiple independent domestications from before the divergence
of X. laevis and X. tropicalis. In contrast, certain other transposases may have
retained catalytic activity required for transposition and could therefore have
been recently amplified. Conclusion: Multiple domestication of certain
transposases and prolonged conservation of the catalytic activity in others
suggest that Kolobok superfamily transposons were involved in complex, mutually
beneficial relationships with their Xenopus hosts. Some transposases may serve to
activate long-lived T2-MITE subfamilies.
PMID- 29946485
TI - Norwegian nursing students' evaluation of vSim(r) for Nursing.
AB - Background: vSim(r) for Nursing is the first web-based platform linked to the
nursing education curriculum. It is an American simulation tool, developed in
2014 through a collaboration between Wolters Kluwer Health, Laerdal Medical and
the National League for Nursing. To our knowledge, no studies have evaluated
vSim(r) for Nursing from the nursing students' perspective in Norway. The aim of
the study was to evaluate second year Norwegian nursing students' experiences
with the virtual clinical simulation scenario in surgical nursing from vSim(r)
for Nursing. Methods: A descriptive and a convergent mixed method design was
utilised. The method comprised a 7-item questionnaire with five open-ended
questions. Sixty-five nursing students participated in the study. Results: The
majority of Norwegian nursing students evaluated the virtual clinical scenario in
surgical nursing from vSim(r) for Nursing useful, realistic and educational in
preparing for clinical placement in surgical care. However, a small portion of
the nursing students had trouble understanding and navigating the American
vSim(r) for Nursing program. Conclusions: Introducing virtual simulation tools
into the nursing education encompasses faculty and student preparation, guidance
from faculty members during the simulation session and support for students who
are facing difficulties with the simulation program.
PMID- 29946484
TI - Stepwise participation of HGF/MET signaling in the development of migratory
muscle precursors during vertebrate evolution.
AB - Background: The skeletal musculature of gnathostomes, which is derived from
embryonic somites, consists of epaxial and hypaxial portions. Some hypaxial
muscles, such as tongue and limb muscles, undergo de-epithelialization and
migration during development. Delamination and migration of these myoblasts, or
migratory muscle precursors (MMPs), is generally thought to be regulated by
hepatocyte growth factor (HGF) and receptor tyrosine kinase (MET) signaling.
However, the prevalence of this mechanism and the expression patterns of the
genes involved in MMP development across different vertebrate species remain
elusive. Results: We performed a comparative analysis of Hgf and Met gene
expression in several vertebrates, including mouse, chicken, dogfish
(Scyliorhinus torazame), and lamprey (Lethenteron camtschaticum). While both Hgf
and Met were expressed during development in the mouse tongue muscle, and in limb
muscle formation in the mouse and chicken, we found no clear evidence for the
involvement of HGF/MET signaling in MMP development in shark or lamprey embryos.
Conclusions: Our results indicate that the expressions and functions of both Hgf
and Met genes do not represent shared features of vertebrate MMPs, suggesting a
stepwise participation of HGF/MET signaling in MMP development during vertebrate
evolution.
PMID- 29946486
TI - The making of evidence-informed health policy in Cambodia: knowledge,
institutions and processes.
AB - Introduction: In global health discussions, there have been widespread calls for
health policy and programme implementation to be informed by the best available
evidence. However, recommendations in the literature on knowledge translation are
often decontextualised, with little attention to the local systems of
institutions, structures and practices which can direct the production of
evidence and shape whether or how it informs health decisions. This article
explores these issues in the country setting of Cambodia, where the Ministry of
Health has explicitly championed the language of evidence-based approaches to
policy and planning. Methods: Research for this paper combined multiple sources
and material, including in-depth interviews with key informants in Phnom Penh and
the analysis of documentary material and publications. Data collection and
analysis focused on two key domains in evidence advisory systems: domestic
capacities to generate health policy-relevant evidence and institutional
mechanisms to monitor, evaluate and incorporate evidence in the policy process.
Results: We identified a number of structural arrangements that may increasingly
work to facilitate the supply of health-related data and information, and their
use to inform policy and planning. However, other trends and features appear to
be more problematic, including gaps between research and public health priorities
in the country, the fragmented nature of research activities and information
systems, the lack of a national policy to support and guide the production and
use of evidence for health policy, and challenges to the use of evidence for
intersectoral policy-making. Conclusions: In Cambodia, as in other low/middle
income countries, continued investments to increase the supply and quality of
health data and information are needed, but greater attention should be paid to
the enabling institutional environment to ensure relevance of health research
products and effective knowledge management.
PMID- 29946488
TI - Variation in cost and performance of routine immunisation service delivery in
India.
AB - A comprehensive understanding of the costs of routine vaccine delivery is
essential for planning, budgeting and sustaining India's Universal Immunisation
Programme. India currently allocates approximately US$25 per child for vaccines
and operational costs. This budget is prepared based on historical expenditure
data as information on cost is not available. This study estimated the cost of
routine immunisation services based on a stratified, random sample of 255 public
health facilities from 24 districts across seven states-Bihar, Gujarat, Kerala,
Meghalaya, Punjab, Uttar Pradesh and West Bengal. The economic cost for the
fiscal year 2013-2014 was measured by adapting an internationally accepted
approach for the Indian context. Programme costs included the value of personnel,
vaccines, transport, maintenance, training, cold chain equipment, building and
other recurrent costs. The weighted average national level cost per dose
delivered was US$2.29 including vaccine costs, and the cost per child vaccinated
with the third dose of diphtheria-pertussis-tetanus (DPT) vaccine (a proxy for
full immunisation) was US$31.67 (at 2017 prices). There was wide variation in the
weighted average state-level cost per dose delivered inclusive of vaccine costs
(US$1.38 to US$2.93) and, for the cost per DTP3 vaccinated child (US$20.08 to
US$34.81). Lower costs were incurred by facilities and districts that provided
the largest number of doses of vaccine. Out of the total cost, the highest amount
(57%) was spent on personnel. This costing study, the most comprehensive
conducted to date in India, provides evidence, which should help improve planning
and budgeting for the national programme. The budget generally considers
financial costs, while this study focused on economic costs. For using this
study's results for planning and budgeting, the collected data can be used to
extract the relevant financial costs. Variation in cost per dose and doses
administered across facilities, districts and states need to be further
investigated to understand the drivers of cost and measure the efficiency of
service delivery.
PMID- 29946487
TI - Predicted distribution and burden of podoconiosis in Cameroon.
AB - Introduction: Understanding the number of cases of podoconiosis, its geographical
distribution and the population at risk are crucial to estimating the burden of
this disease in endemic countries. We assessed each of these using nationwide
data on podoconiosis prevalence in Cameroon. Methods: We analysed data arising
from two cross-sectional surveys in Cameroon. The dataset was combined with a
suite of environmental and climate data and analysed within a robust statistical
framework, which included machine learning-based approaches and geostatistical
modelling. The environmental limits, spatial variation of predicted prevalence,
population at risk and number of cases of podoconiosis were each estimated.
Results: A total of 214 729 records of individuals screened for podoconiosis were
gathered from 748 communities in all 10 regions of Cameroon. Of these screened
individuals, 882 (0.41%; 95% CI 0.38 to 0.44) were living with podoconiosis. High
environmental suitability for podoconiosis was predicted in three regions of
Cameroon (Adamawa, North West and North). The national population living in areas
environmentally suitable for podoconiosis was estimated at 5.2 (95% CI 4.7 to
5.8) million, which corresponds to 22.3% of Cameroon's population in 2015.
Countrywide, in 2015, the number of adults estimated to be suffering from
podoconiosis was 41 556 (95% CI, 1170 to 240 993). Four regions (Central,
Littoral, North and North West) contributed 61.2% of the cases. Conclusion: In
Cameroon, podoconiosis is more widely distributed geographically than was
initially expected. The number of cases and the population at risk are
considerable. Expanding morbidity management and follow-up of cases is of utmost
necessity. Promotion of footwear use and regular foot hygiene should be at the
forefront of any intervention plan.
PMID- 29946490
TI - Correction: Distribution and determinants of pneumonia diagnosis using integrated
management of childhood illness guidelines: a nationally representative study in
Malawi.
AB - [This corrects the article DOI: 10.1136/bmjgh-2017-000506.].
PMID- 29946491
TI - Correction: Comparing and contrasting 'innovation platforms' with other forms of
professional networks for strengthening primary healthcare systems for Indigenous
Australians.
AB - [This corrects the article DOI: 10.1136/bmjgh-2017-000683.].
PMID- 29946489
TI - Hubris, humility and humanity: expanding evidence approaches for improving and
sustaining community health programmes.
AB - Community-based approaches are a critical foundation for many health outcomes,
including reproductive, maternal, newborn and child health (RMNCH). Evidence is a
vital part of strengthening that foundation, but largely focuses on the technical
content of what must be done, rather than on how disparate community actors
continuously interpret, implement and adapt interventions in dynamic and varied
community health systems. We argue that efforts to strengthen evidence for
community programmes must guard against the hubris of relying on a single
approach or hierarchy of evidence for the range of research questions that arise
when sustaining community programmes at scale. Moving forward we need a broader
evidence agenda that better addresses the implementation realities influencing
the scale and sustainability of community programmes and the partnerships
underpinning them if future gains in community RMNCH are to be realised. This
will require humility in understanding communities as social systems, the
complexity of the interventions they engage with and the heterogeneity of
evidence needs that address the implementation challenges faced. It also entails
building common ground across epistemological word views to strengthen the
robustness of implementation research by improving the use of conceptual
frameworks, addressing uncertainty and fostering collaboration. Given the
complexity of scaling up and sustaining community RMNCH, ensuring that evidence
translates into action will require the ongoing brokering of relationships to
support the human creativity, scepticism and scaffolding that together build
layers of evidence, critical thinking and collaborative learning to effect
change.
PMID- 29946492
TI - Neonatal Contrast Sensitivity and Visual Acuity: Basic Psychophysics.
AB - Purpose: This research was prospectively designed to determine whether a 0.083
cycles per degree (cy/deg) (20/7200) square-wave stimulus is a good choice for
clinical measurement of newborn infants' contrast sensitivity and whether the
contrast sensitivity function (CSF) of the newborn infant is band-pass. The
results were retrospectively analyzed to determine whether the method of constant
stimuli (MCS) and the descending method of limits (dLIM) yielded similar results.
Methods: In across-subjects experimental designs, a pilot experiment used MCS (N
= 47 visual acuity; N = 38 contrast sensitivity at 0.083 cy/deg), and a main
experiment used dLIM (N = 22 visual acuity; N = 22 contrast sensitivity at 0.083
cy/deg; N = 21 at 0.301 cy/deg) to measure visual function in healthy newborn
infants. Three candidate CSFs estimated maximum neonatal contrast sensitivity.
MCS and dLIM psychometric functions were compared while taking the stimulus
presentation protocols into account. Results: The band-pass CSF fit the data
best, with a peak sensitivity near 0.31 at 0.22 cy/deg. However, the 0.083 cy/deg
square-wave stimulus underestimated the best performance of newborn infants by
less than 0.15 log10 units. MCS and dLIM data agreed well when the stimulus
presentation contingencies were taken into account. Conclusions: Newborn contrast
sensitivity is well measured using a 0.083 cy/deg square-wave target, regardless
of which CSF shape is correct. MCS and dLIM yield wholly comparable results, with
no evidence to suggest effects of other factors such as infant inattention or
examiner impatience. Translational Relevance: These measurements open the way for
clinical behavioral measurement of infant visual acuity and contrast sensitivity
in the neonatal period.
PMID- 29946493
TI - Is Ahmed Glaucoma Valve Consistent in Performance?
AB - Purpose: To investigate the mechanism of action and consistency in flow
characteristics of the Ahmed glaucoma valve (AGV) under simulated physiological
conditions in-vitro and to evaluate whether resistance during priming has any
effect on performance of the device. Methods: Each newly opened AGV device was
connected to a digital manometer and was primed with normal saline. The device
was then placed in a saline bath and connected to an open manometer, a digital
manometer, and an infusion pump. Saline was infused at a rate of 3 MUL/min for 24
hours. Digital manometer readings were recorded at 4 Hz. Results: Data obtained
from 9 devices are presented as medians (ranges). The priming pressure was 1130
(835, 1625) mm Hg. Pressure versus time curves showed two distinct phases;
transient and steady phases. The transient phase peak pressure was 24 (13, 45) mm
Hg. In the steady phase, opening and closing pressures were 13 (10, 17) and 7 (4,
9) mm Hg, respectively; the valve leaflets briefly opened every 73.9 (51, 76.6)
minutes and the fluctuation of pressure (difference between opening and closing
pressures) was 6 (3, 9) mm Hg. The Spearman correlation coefficient between
priming and opening and priming and closing pressure was rho = -0.13 (P = 0.72)
and rho = -0.36 (P = 0.33), respectively. Conclusions: The device showed
functionality like a valve. The resistance during priming did not affect opening
and closing pressures of the AGV. This study showed variable in vitro performance
of the AGV. Translational Relevance: These laboratory findings might, at least
partly, explain the variability in the clinical outcome of the device.
PMID- 29946494
TI - Characterization of Retinitis Pigmentosa Using Fluorescence Lifetime Imaging
Ophthalmoscopy (FLIO).
AB - Purpose: We investigated fundus autofluorescence (FAF) lifetimes in patients with
retinitis pigmentosa (RP) using fluorescence lifetime imaging ophthalmoscopy
(FLIO). Methods: A total of 33 patients (mean age, 40.0 +/- 17.0 years) with RP
and an age-matched healthy group were included. The Heidelberg FLIO was used to
detect FAF decays in short (SSC; 498-560 nm) and long (LSC; 560-720 nm) spectral
channels. We investigated a 30 degrees retinal field and calculated the
amplitude-weighted mean fluorescence lifetime (taum). Additionally, macular
pigment measurements, macular optical coherence tomography (OCT) scans, fundus
photographs, visual fields, and fluorescein angiograms were recorded. Genetic
studies were performed on nearly all patients. Results: In RP, FLIO shows a
typical pattern of prolonged taum in atrophic regions in the outer macula (SSC,
419 +/- 195 ps; LSC, 401 +/- 111 ps). Within the relatively preserved retina in
the macular region, ring-shaped patterns were found, most distinctive in patients
with autosomal dominant RP inheritance. Mean FAF lifetimes were shortened in
rings in the LSC. Central areas remained relatively unaffected. Conclusions: FLIO
uniquely presents a distinct and specific signature in eyes affected with RP. The
ring patterns show variations that indicate genetically determined pathologic
processes. Shortening of FAF lifetimes in the LSC may indicate disease
progression, as was previously demonstrated for Stargardt disease. Therefore,
FLIO might be able to indicate disease progression in RP as well. Translational
Relevance: Hyperfluorescent FLIO rings with short FAF lifetimes may provide
insight into the pathophysiologic disease status of RP-affected retinas
potentially providing a more detailed assessment of disease progression.
PMID- 29946495
TI - The Reliability of Cone Density Measurements in the Presence of Rods.
AB - Purpose: Recent advances in adaptive optics scanning light ophthalmoscopy (AOSLO)
have enabled visualization of cone inner segments through nonconfocal split
detection, in addition to rod and cone outer segments revealed by confocal
reflectance. Here, we examined the interobserver reliability of cone density
measurements in both AOSLO imaging modalities. Methods: Five normal subjects
(nine eyes) were imaged along the horizontal and vertical meridians using a
custom AOSLO with confocal and nonconfocal split-detection modalities. The
resulting images were montaged using a previously described semiautomatic
algorithm. Regions of interest (ROIs) were selected from the confocal montage at
190 MUm, and from split-detection and confocal montages at 900 and 1800 MUm from
the fovea. Four observers (three experts, one naive) manually identified cone
locations in each ROI, and these locations were used to calculate bound
densities. Intraclass correlation coefficients and Dice's coefficients were
calculated to assess interobserver agreement. Results: Interobserver agreement
was high in cone-only images (confocal 190 MUm: 0.85; split-detection 900 MUm:
0.91; split-detection 1800 MUm: 0.89), moderate in confocal images at 900 MUm
(0.68), and poor in confocal images at 1800 MUm (0.24). Excluding the naive
observer data substantially increased agreement within confocal images (190 MUm:
0.99; 900 MUm: 0.80; 1800 MUm: 0.68). Conclusions: Interobserver measurements of
cone density are more reliable in rod-free retinal images. Moreover, when using
manual cell identification, it is essential that observers are trained,
particularly for confocal AOSLO images. Translational Relevance: This study
underscores the need for additional reliability studies in eyes containing
pathology where identifying cones can be substantially more difficult.
PMID- 29946496
TI - Development of a Visual Field Simulation Model of Longitudinal Point-Wise
Sensitivity Changes From a Clinical Glaucoma Cohort.
AB - Purpose: To develop a new visual field simulation model that can recreate real
world longitudinal results at a point-wise level from a clinical glaucoma cohort.
Methods: A cohort of 367 glaucoma eyes from 265 participants seen over 10.1 +/-
2.5 years were included to obtain estimates of "true" longitudinal visual field
point-wise sensitivity and estimates of measurement variability. These two
components were then combined to reconstruct visual field results in a manner
that accounted for correlated measurement error. To determine how accurately the
simulated results reflected the clinical cohort, longitudinal variability
estimates of mean deviation (MD) were determined by calculating the SD of the
residuals from linear regression models fitted to the MD values over time for
each eye in the simulated and clinical cohorts. The new model was compared to a
previous model that does not account for spatially correlated errors. Results:
The SD of all the residuals for the clinical and simulated cohorts was 1.1 dB
(95% confidence interval [CI]: 1.1-1.2 dB) and 1.1 dB (95% CI: 1.1-1.1 dB),
respectively, whereas it was 0.4 dB (95% CI: 0.4-0.4 dB) using the previous
simulation model that did not account for correlated errors. Conclusions: A new
simulation model accounting for correlated measurement errors between visual
field locations performed better than a previous model in estimating visual field
variability in glaucoma. Translational Relevance: This model can provide a
powerful framework to better understand use of visual field testing in clinical
practice and trials and to evaluate new methods for detecting progression.
PMID- 29946497
TI - Surveillance Screening in Li-Fraumeni Syndrome: Raising Awareness of False
Positives.
AB - Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome inherited in
an autosomal dominant fashion that involves a germline mutation of tumor protein
53 (TP53). With the advent of more accessible and accurate genetic testing
methods, along with more widespread knowledge of LFS, asymptomatic carriers can
now be more easily identified. No general surveillance protocols were previously
recommended other than routine physical exams and breast and colon cancer
screening at younger ages, primarily due to questions involving efficacy, cost,
and clinical benefits. With more data now available to support the implementation
of a surveillance protocol for cancer predisposition syndromes such as LFS,
preventative screening has become a national standard of care. However, as
surveillance becomes more integrated into patient care, the benefits and risks
must be further evaluated. We briefly describe our institutional experience with
surveillance screening in LFS and describe two patients in depth where
surveillance imaging brought to light false positives that led to increased
utilization of resources and concern for new malignancy. Though the benefits of
surveillance are clear, it is important to understand the potential for false
positives involved with instituting this practice. Continued research of this
topic is thus warranted, perhaps with larger prospective studies, to better
capture the survival benefits of patients undergoing surveillance screening and
more comprehensively understand the incidence of false positives.
PMID- 29946498
TI - Rapid Sequence Intubation in Traumatic Brain-injured Adults.
AB - Deciding on proper medication administration for the traumatic brain injury (TBI)
patient undergoing intubation can be daunting and confusing. Pretreatment with
lidocaine and/or vecuronium is no longer recommended; however, high-dose fentanyl
can be utilized to help blunt the sympathetic stimulation of intubation.
Induction with etomidate is recommended; however, ketamine can be considered in
the proper patient population, such as those with hypotension. Paralysis can be
performed with either succinylcholine or rocuronium, with the caveat that
rocuronium can lead to delays in proper neurological examinations due to
prolonged paralysis. Recommendations for post-intubation continuous sedation
medications include a combination propofol and fentanyl in the
normotensive/hypertensive patient population. A combination midazolam and
fentanyl or ketamine alone can be considered in the hypotensive patient.
PMID- 29946499
TI - Impact of Urinalysis on Medical Decision-making and Length of Stay.
AB - Introduction The emergency department (ED) is under pressure to meet length of
stay (LOS) metrics for care in the ED. An aspect that we propose affects LOS is
the order for urine sample collection and subsequent urinalysis (UA) as both are
time consuming steps. This project's primary goals are to determine if ordering a
UA increases LOS and how often UA contributes to clinical decision-making and/or
disposition decisions in the ED. Secondary objectives were to identify factors
that contribute to the ordering of a UA and to decipher if LOS was more impacted
in patients who were discharged vs. admitted to the hospital. Methods
Retrospective chart review was conducted of patients who presented to our ED in
April 2016 during 12 consecutive days. Data were abstracted onto a data
collection sheet with the abstractor blinded to study hypotheses. Variables
included whether a UA was ordered, times of UA order and result, who ordered the
UA (mid-level provider [MLP] vs. physician), whether the UA was cancelled,
whether the UA result influenced clinical decision-making (based on the medical
decision-making section of the physician chart) or disposition decision, LOS,
age, and gender. Descriptive statistics and multivariable regression analysis
were used to analyze relationships between the variables collected and their
influence on LOS. Results The overall median LOS was 157 minutes, with an
interquartile range (IQR) of 81 to 246 minutes. For discharged patients, it was
142 minutes, with an IQR of 46 to 236 minutes. For admitted patients, it was 177
minutes, with an IQR of 118 to 260 minutes. Amongst admitted patients,
multivariable regression analysis demonstrated that the following factor was
associated with increased LOS: being seen first by the provider-in-triage (PIT)
then physician in main ED (p < 0.0001). Amongst discharged patients,
multivariable regression analysis demonstrated that the following factors were
associated with increased LOS: being seen first by the PIT then physician in main
ED (p = 0.0296), being seen by MLP only (p < 0.0001), having a UA ordered (p =
0.0005), being seen on weekend (p = 0.0166), and being an older patient (p =
0.0475). The UA was cancelled in 9% of our patients, and in 60% of cases, these
UAs were ordered by the PIT. Patient disposition decision was made prior to UA
resulting in 60 cases (25%). The UA was used in clinical decision-making in 118
cases (66%). The following predictor factors were associated via univariate
analysis with using a UA for decision-making: being female (p = 0.0050, 95% CI:
0.0068-0.378), being an older patient (p < 0.0001, 95% CI: -0.010 to -0.004),
being first seen by the PIT and then a physician (p = 0.0486, 95% CI: 0.0048
0.1555), and discharged patients (p < 0.0001, 95% CI: -0.6749 to -0.4487).
Conclusion Our results suggest that having a UA ordered increased ED LOS,
especially in patients who are ultimately discharged. In our ED, routine UAs are
ordered more often by MLPs than physicians. A routine UA may not impact clinical
decision-making up to 33% of the time, nor alter disposition decision one out of
four times. Given that 9% have the test eventually cancelled, one should
reconsider the utility in ordering routine UAs in ED patients, as they increase
LOS and place an additional burden on the patient and the ED personnel.
PMID- 29946500
TI - Fibrosing Mediastinitis: Uncommon Life-threatening Complication of
Histoplasmosis.
AB - Histoplasmosis involving mediastinum is very rare which can present as a
mediastinal mass or fibrosing mediastinitis. Fibrosing mediastinitis can be life
threatening if left untreated due to the involvement of the surrounding visceral
and vascular structures. We present an interesting case of fibrosing
mediastinitis due to histoplasmosis presented with palpitations, chest pain and
dyspnea. The patient had mediastinal and hilar lymphadenopathy with calcification
on chest imaging. The patient was diagnosed on lymph node biopsy and treated with
antifungals.
PMID- 29946501
TI - A Case of Bullous Pemphigoid: A Prevalent and Potentially Fatal Condition.
AB - Bullous pemphigoid is the most common of the blistering disorders. It is most
commonly found in the elderly and is diagnosed based on clinical, histologic, and
immunologic criteria. It presents clinically with diffuse eczematous, pruritic,
urticaria-like lesions, with the later appearance of tense bullae or blistering
lesions typically filled with clear fluid. Histologically, a sub-epidermal
blister is seen and immunofluorescence shows immunoglobulin G antibodies directed
against the structural components of the keratinocytic hemidesmosomal proteins
BP180 and BP230. Multiple treatment modalities are present for this condition,
including anti-inflammatory medications, medications that reduce antibody
formation, and treatments to increase the elimination of antibodies. The aim of
this case report is to present a classic case of this condition, to highlight an
awareness of differing treatment options, and to advocate referral to a
dermatologist given its potential severity.
PMID- 29946502
TI - Percutaneous Radiofrequency Ablation for the Treatment of Peripheral Nerve Sheath
Tumors: A Case Report and Review of the Literature.
AB - Peripheral nerve sheath tumors (PNSTs) may arise sporadically or in the presence
of genetic disorders, including neurofibromatosis (NF) types 1 and 2,
schwannomatosis, and in patients with large genetic deletions involving the
CDKN2A gene. Surgical resection is the treatment of choice for symptomatic PNSTs
and offers patients a potential cure; however, pre-existing conditions or tumor
location may limit a patient's surgical options. Radiofrequency ablation (RFA)
may provide an alternative therapeutic strategy for the treatment of selected
PNSTs that are not amenable to surgical resection. Here, we present a case report
of a 49-year-old patient with multiple neurofibromas who underwent RFA treatment
of two symptomatic retroperitoneal neurofibromas and review previously reported
cases of percutaneous treatment of PNSTs.
PMID- 29946503
TI - Anomalous Origin of Coronary Arteries Arising from the Right Coronary Cusp: A
Rare Presentation.
AB - The anomalous origin of coronaries is rare. The purpose of this case report is to
show a rare anomalous origin of coronaries. A 64-year-old female presented with
chest pain that was typical in nature. The patient had left heart catheterization
that showed an anomalous origin of coronaries, where all the coronaries were
arising from the right coronary cusp. The patient had a significant disease in
the distal left anterior descending artery, but it was a small vessel. Medical
management was chosen. This is a rare presentation of the coronary anatomy.
PMID- 29946505
TI - Unresponsive Intractable Chronic Headache With Sitagliptin.
AB - Sitagliptin is an anti-diabetic medication within the dipeptidyl peptidase 4
(DPP4) inhibitor class used as a single agent or in combination therapy. It is a
well-studied and well-tolerated medication with commonly reported adverse events
of upper respiratory tract infections, nasopharyngitis, headache, and
gastrointestinal (GI) upset. Post-marketing reports have also identified
associations with acute pancreatitis and joint pain. Here, we report a case of
type II diabetes with chronic headache which resolved rapidly after
discontinuation of sitagliptin. Our case demonstrates the need for continuous
monitoring and post-marketing surveillance for drugs with tolerable side effect
profile. Also, increasing patient and physician awareness of long-term side
effects of these commonly used medications is essential for adequate patient
safety and quality care.
PMID- 29946504
TI - Diffuse Large B-cell Lymphoma Occurring with Rhinophyma: A Case Report.
AB - Rhinophyma is the final stage in the evolution of acne rosacea, a common
vasoactive dermatosis. Individuals with rhinophyma present with a typical,
disfiguring nasal appearance consisting of bulbous enlargement, erythema, and
telangiectasia with a sebaceous, oily skin surface. This classic appearance
permits a facile diagnosis but may also lead the physician to overlook a
coexistent malignancy. We report the occurrence of a diffuse large B-cell
lymphoma (DLBCL) arising synchronously with a marked rhinophyma. A wide local
excision of the malignancy was performed, and the defect was reconstructed with
forehead flaps. The rhinophyma was treated with a skin graft and cheek flaps.
Following surgery, chemotherapy was used to manage the systemic disease. This
case demonstrates the necessity for clinical scrutiny in the diagnosis and
treatment of rhinophyma. It is imperative to entertain a high degree of suspicion
when non-typical changes are observed within a rhinophymatous lesion or in
adjacent areas of the nose.
PMID- 29946506
TI - Fitness Measures Among Boy Scouts Completing the Personal Fitness Merit Badge.
AB - Introduction A formative framework for positive lifestyle and health behaviors is
established during adolescence. The Boy Scouts of America (BSA) is one
organization that promotes healthy lifestyles among adolescent males and includes
earning the Personal Fitness Merit Badge (PFMB). Despite the BSA Oath "to keep
myself physically strong", there is a paucity of evidence describing fitness test
(FT) outcomes or correlations between FT and variables including age or body mass
index (BMI) among Boy Scouts. Therefore, the purpose of this study is to describe
and correlate FT to age and BMI among adolescent Boy Scouts. Methods A
prospective study design recruited Boy Scouts aged 11-17 years from Southeast
Michigan using a sample of convenience. After securing physician clearance to
participate, FT measures were performed utilizing previously established
methodology. Third year doctor of physical therapy students trained in the
measurement protocol performed the FT measures. Measures encompassed those
required for the PFMB: BMI, pull-ups, push-ups, sit and reach flexibility test
(SRF), sit-ups, and the one mile run (1MR). Data was analyzed using descriptive
statistics, a Kruskal-Wallis test examined relationships between BMI and FT, and
a nonparametric Spearman correlation examined correlations between FT performance
and both age and BMI with statistical significance set at less than 0.05. Results
Ninety-nine Boy Scouts, whose mean age was 12.6 years (SD 1.4), met the inclusion
criteria. The mean BMI was 21.5 (kg/height (cm)) 2 (SD 5.4) with eight scouts
meeting criteria of underweight, 56 normal weight, 14 overweight, and 21 obese.
Fitness test results were as follows: pull-ups 1.75 (SD 2.7), push-ups 18.0 (SD
10.6), SRF 21.2 cm (SD 10.5), sit-ups 28.9 (SD 8.7), and the 1MR run 616.5
seconds (SD 156.8). When comparing normal weight scouts to overweight and obese
scouts, a significantly higher frequency of pull-ups (p=0.002, p=.001), push-ups
(p=0.02, p=0.03), sit-ups (p=0.01, p=0.003,), and decreased time for completion
on the 1MR (p=0.001, p=0.001) was identified, respectively. Furthermore, while no
correlations were identified by age, a negative correlation was identified
between increased sit-up frequency (r=-0.36, p=0.001) and decreased 1MR time
performance (r=0.39, p=0.001) and a higher BMI. Discussion While prior evidence
suggests improved FT scores in adolescent males with advancing age, this was not
observed. Less favorable PFMB required FT performance with an increased BMI among
Boy Scouts is in congruence with prior reports for adolescent males. Conclusion
Variations in FT performance levels were observed among Boy Scouts completing the
initial FT requirements of the PFMB. However, correlations between higher BMI and
less favorable FT performance were detected.
PMID- 29946507
TI - Immunization Against Group B Streptococci vs. Intrapartum Antibiotic Prophylaxis
in Peripartum Pregnant Women and their Neonates: A Review.
AB - Group B streptococcus (GBS) is an organism that has an immense global impact on
neonatal morbidity and mortality. GBS is known to colonize the gastrointestinal
and genitourinary tracts of infected pregnant women. Transmission to the neonate
is achieved during labor and delivery. Complications of neonatal infection
include sepsis, meningitis, and pneumonia. Preventative measures are needed to
reduce the disease burden. The current method of prophylaxis being utilized is
intrapartum antibiotics. Though effective, it presents limitations that include a
required, lengthy duration of treatment, increased antibiotic resistance, and
lack of late-onset disease coverage. Recent studies are exploring alternative
methods of prophylaxis such as vaccination. Vaccination provides coverage of both
early and late-onset disease to infected women who are unable to complete the
required four hours of antibiotic course intrapartum, women with resistance to
antibiotic infections, and women delivering in resource-poor areas without access
to antibiotics. An investigational CRM197 conjugated trivalent vaccine has shown
a good immunogenicity profile against the three most prevalent serotypes. The
vaccine induced antibodies freely cross the placenta and persist in a neonate for
up to 90 days after birth. Additionally, the vaccine possesses a safety profile
free of any serious systemic adverse effects and only mild pain at the injection
site. Future studies should focus on investigating the effect of the vaccine on
maternal rectovaginal acquisition and subsequent vaginal colonization, as well as
the expansion of vaccine coverage to all 10 serotypes identified worldwide in
order to facilitate its use in resource-poor areas of the world with inadequate
antibiotic availability. If available, such a vaccine can serve as an effective
supplement to current guidelines of antibiotic prophylaxis against GBS in
peripartum women and their neonates.
PMID- 29946508
TI - Investigation of serotonergic Parkinson's disease-related covariance pattern
using [11C]-DASB/PET.
AB - We used positron emission tomography imaging with [11C]-3-amino-4-(2
dimethylaminomethylphenylsulfanyl)- benzonitrile (DASB) and principal component
analysis to investigate whether a specific Parkinson's disease (PD)-related
spatial covariance pattern could be identified for the serotonergic system. We
also explored if non-manifesting leucine-rich repeat kinase 2 (LRRK2) mutation
carriers, with normal striatal dopaminergic innervation as measured with [11C]
dihydrotetrabenazine (DTBZ), exhibit a distinct spatial covariance pattern
compared to healthy controls and subjects with manifest PD. 15 subjects with
sporadic PD, eight subjects with LRRK2 mutation-associated PD, nine LRRK2 non
manifesting mutation carriers, and nine healthy controls participated in the
study. The analysis was applied to the DASB non-displaceable binding potential
values evaluated in 42 pre-defined regions of interest. PD was found to be
associated with a specific spatial covariance pattern, comprising relatively
decreased DASB binding in the caudate, putamen and substantia nigra and
relatively preserved binding in the hypothalamus and hippocampus; the expression
of this pattern in PD subjects was significantly higher than in healthy controls
(P < 0.001) and correlated significantly with disease duration (P < 0.01) and
with DTBZ binding in the more affected putamen (P < 0.01). The LRRK2 non
manifesting mutation carriers expressed a different pattern, also significantly
different from healthy controls (P < 0.001), comprising relatively decreased DASB
binding in the pons, pedunculopontine nucleus, thalamus and rostral raphe
nucleus, and with relatively preserved binding in the hypothalamus, amygdala,
hippocampus and substantia nigra. This pattern was not present in either sporadic
or LRRK2 mutation-associated PD subjects. These findings, although obtained with
a relatively limited number of subjects, suggest that specific and overall
distinct spatial serotonergic patterns may be associated with PD and LRRK2
mutations. Alterations in regions where relative upregulation is observed in both
patterns may be indicative of compensatory mechanisms preceding or protecting
from disease manifestation.
PMID- 29946510
TI - SPG11 mutations cause widespread white matter and basal ganglia abnormalities,
but restricted cortical damage.
AB - SPG11 mutations are the major cause of autosomal recessive Hereditary Spastic
Paraplegia. The disease has a wide phenotypic variability indicating many regions
of the nervous system besides the corticospinal tract are affected. Despite this,
anatomical and phenotypic characterization is restricted. In the present study,
we investigate the anatomical abnormalities related to SPG11 mutations and how
they relate to clinical and cognitive measures. Moreover, we aim to depict how
the disease course influences the regions affected, unraveling different
susceptibility of specific neuronal populations. We performed clinical and
paraclinical studies encompassing neuropsychological, neuroimaging, and
neurophysiological tools in a cohort of twenty-five patients and age matched
controls. We assessed cortical thickness (FreeSurfer software), deep grey matter
volumes (T1-MultiAtlas tool), white matter microstructural damage (DTI
MultiAtlas) and spinal cord morphometry (Spineseg software) on a 3 T MRI scan.
Mean age and disease duration were 29 and 13.2 years respectively. Sixty-four
percent of the patients were wheelchair bound while 84% were demented. We were
able to unfold a diffuse pattern of white matter integrity loss as well as basal
ganglia and spinal cord atrophy. Such findings contrasted with a restricted
pattern of cortical thinning (motor, limbic and parietal cortices).
Electromyography revealed motor neuronopathy affecting 96% of the probands.
Correlations with disease duration pointed towards a progressive degeneration of
multiple grey matter structures and spinal cord, but not of the white matter.
SPG11-related hereditary spastic paraplegia is characterized by selective
neuronal vulnerability, in which a precocious and widespread white matter
involvement is later followed by a restricted but clearly progressive grey matter
degeneration.
PMID- 29946509
TI - Diffusion-weighted imaging evidence of altered white matter development from late
childhood to early adulthood in Autism Spectrum Disorder.
AB - Autism Spectrum Disorder (ASD) is thought to reflect disrupted development of
brain connectivity characterized by white matter abnormalities and
dyscoordination of activity across brain regions that give rise to core features.
But there is little consensus about the nature, timing and location of white
matter abnormalities as quantified with diffusion-weighted MRI. Inconsistent
findings likely reflect small sample sizes, motion confounds and sample
heterogeneity, particularly different age ranges across studies. We examined the
microstructural integrity of major white matter tracts in relation to age in 38
high functioning ASD and 35 typically developing (TD) participants, aged 8-25,
whose diffusion-weighted scans met strict data-quality criteria and survived
group matching for motion. While there were no overall group differences in
diffusion measures, the groups showed different relations with age. Only the TD
group showed the expected positive correlations of fractional anisotropy with
age. In parallel, axial diffusivity was unrelated to age in TD, but showed
inverse correlations with age in ASD. Younger participants with ASD tended to
have higher fractional anisotropy and axial diffusivity than their TD peers,
while the opposite was true for older participants. Most of the affected tracts -
cingulum bundle, inferior and superior longitudinal fasciculi - are association
bundles related to cognitive, social and emotional functions that are abnormal in
ASD. The manifestations of abnormal white matter development in ASD as measured
by diffusion-weighted MRI depend on age and this may contribute to inconsistent
findings across studies. We conclude that ASD is characterized by altered white
matter development from childhood to early adulthood that may underlie abnormal
brain function and contribute to core features.
PMID- 29946512
TI - Disrupted functional network integrity and flexibility after stroke: Relation to
motor impairments.
AB - Previous studies investigating brain activation present during upper limb
movement after stroke have greatly detailed activity alterations in the ipsi- and
contralesional primary motor cortices (M1). Despite considerable interest in M1,
investigations into the integration and coordination of large-scale functional
networks subserving motor, sensory, and cognitive control after stroke remain
scarce. The purpose of this study was to assess non-static functional
connectivity within whole-brain networks involved in the production of isometric,
visually-paced hand grips. Seventeen stroke patients and 24 healthy controls
underwent functional MRI while performing a series of 50 isometric hand grips
with their affected hand (stroke patients) or dominant hand (control subjects).
We used task-based multivariate functional connectivity to derive spatial and
temporal information of whole-brain networks specifically underlying hand
movement. This technique has the advantage of extracting within-network
commonalities across groups and identifying connectivity differences between
these groups. We further used a nonparametric statistical approach to identify
group differences in regional activity within these task-specific networks and
assess whether such alterations were related to the degree of motor impairment in
stroke patients. Our whole-brain multivariate analysis revealed group differences
in two networks: (1) a motor network, including pre- and postcentral gyri, dorsal
and ventral premotor cortices, as well as supplementary motor area, in which
stroke patients showed reduced task-related activation compared to controls, and
(2) a default-mode network (DMN), including the posterior cingulate cortex,
precuneus, and medial prefrontal cortex, in which patients showed less
deactivation than controls. Within-network group differences revealed decreased
activity in ipsilesional primary sensorimotor cortex in stroke patients, which
also positively correlated with lower levels of motor impairment. Moreover, the
temporal information extracted from the functional networks revealed that stroke
patients did not show a reciprocal DMN deactivation peak following activation of
their motor network. This finding suggests that allocation of functional
resources to motor areas during hand movement may impair their ability to
efficiently switch from one network to another. Taken together, our study expands
our understanding of functional reorganization during motor recovery after a
stroke, and suggests that modulation of ipsilesional sensorimotor activity may
increase the integrity of a whole-brain motor network, contribute to better motor
performance, and optimize network flexibility.
PMID- 29946511
TI - Abnormal cortical gyrification in criminal psychopathy.
AB - Background: Psychopathy is a personality disorder characterized by interpersonal
and emotional abnormalities (e.g., lack of empathy and guilt) and antisocial
behavior. Psychopathy has been associated with a number of structural brain
abnormalities, most notably in orbital frontal and anterior/medial temporal
regions, that may underlie psychopathic individuals' problematic behaviors. Past
research evaluating cortical structure in psychopathy has considered thickness
and volume, but to date no study has investigated differences in cortical
gyrification, a measure of cortical complexity thought to reflect early
neurodevelopmental cortical connectivity. Methods: We measured the local
gyrification index (LGI) in a sample of 716 adult male inmates and performed a
whole brain analysis assessing the relationship between LGI and total and factor
scores on the Hare Psychopathy Checklist-Revised (PCL-R). Results: PCL-R scores
were negatively associated with LGI measures within the right hemisphere in the
midcingulate cortex (MCC) and adjacent regions of the superior frontal gyrus as
well as lateral superior parietal cortex. Additionally, PCL-R Factor 1 scores
(interpersonal/affective traits) predicted less LGI within the right MCC and
adjacent dorsomedial frontal cortex and greater LGI in bilateral occipital
cortex. Scores on PCL-R Factor 2, indicating impulsivity and antisocial
behaviors, did not predict LGI in any regions. Conclusions: These findings
suggest that psychopathy, particularly the interpersonal and affective traits,
are associated with specific structural abnormalities that form during
neurodevelopment and these abnormalities may underlie aberrant brain functioning
in regions important in emotional processing and cognitive control.
PMID- 29946513
TI - Pompe disease treatment with twice a week high dose alglucoside alfa in a patient
with severe dilated cardiomyopathy.
AB - There is limited information regarding ideal dosage of alglucoside alfa in
patients with Infantile Onset Pompe Disease (IOPD). The U.S. Food and Drug
Administration approved alglucoside alfa at dosing of 20 mg/kg every other week,
but there are small studies and case reports suggesting that dosing higher than
this leads to improved ventilator free survival and development without adverse
events. We review the clinical course and short term clinical outcomes one year
following late diagnosis of IOPD in a 3 month old who presented severely affected
and was treated with 40 mg/kg twice a week for 21 infusions until six months of
age then transitioned to 40 mg/kg/week. The patient responded well to 40 mg/kg
twice a week treatment without adverse reactions and significant clinical
improvement.
PMID- 29946515
TI - CPT-II deficiency needs to be detected in army personnel.
PMID- 29946514
TI - Diversity in the incidence and spectrum of organic acidemias, fatty acid
oxidation disorders, and amino acid disorders in Asian countries: Selective
screening vs. expanded newborn screening.
AB - Background: Expanded newborn screening (ENBS) utilizing tandem mass spectrometry
(MS/MS) for inborn metabolic diseases (IMDs), such as organic acidemias (OAs),
fatty acid oxidation disorders, (FAODs), and amino acid disorders (AAs), is
increasingly popular but has not yet been introduced in many Asian countries.
This study aimed to determine the incidence rates of OAs, FAODs, and AAs in Asian
countries and Germany using selective screening and ENBS records. Materials and
methods: Selective screening for IMDs using gas chromatography-mass spectrometry
and MS/MS was performed among patients suspected to be afflicted in Asian
countries (including Japan, Vietnam, China, and India) between 2000 and 2015, and
the results from different countries were compared. Similarly, ENBS results from
Japan, South Korea, Taiwan, and Germany were compared. Additionally, the results
of selective screening and ENBS in Japan were compared. Results: Among 39,270
patients who underwent selective screening, IMDs were detected in 1170.
Methylmalonic acidemia was frequently identified in several countries, including
Japan (81/377 diagnosed IMDs), China (94/216 IMDs), and India (72/293 IMDs). In
Vietnam, however, beta-ketothiolase deficiency was particularly frequent (33/250
IMDs). ENBS yielded differences in overall IMD rates by country: 1:8557 in Japan,
1:7030 in Taiwan, 1:13,205 in South Korea, and 1:2200 in Germany. Frequently
discovered diseases included propionic acidemia (PPA) and phenylketonuria (PKU)
in Japan, 3-methylcrotonyl-CoA carboxylase deficiency (MCCD) and PKU in Taiwan,
MCCD and citrullinemia type I in South Korea, and PKU and medium-chain acyl-CoA
dehydrogenase deficiency in Germany. Furthermore, in Japan, selective screening
and ENBS yielded respective PPA frequencies of 14.7% and 49.4% among all organic
acidemias. Conclusion: The incidence rates of IMDs vary by country. Moreover, the
disease spectra of IMDs detected via selective screening differ from those
detected via ENBS.
PMID- 29946516
TI - Impact of tobacco cessation on tuberculosis control.
PMID- 29946517
TI - Extending the reach of integrated TB-HIV services with community health workers.
PMID- 29946518
TI - Building the capacity of public health programmes to become data rich,
information rich and action rich.
AB - Good quality, timely data are the cornerstone of health systems, but in many
countries these data are not used for evidence-informed decision making and/or
for improving public health. The SORT IT (Structured Operational Research and
Training Initiative) model has, over 8 years, trained health workers in low- and
middle-income countries to use data to answer important public health questions
by taking research projects through to completion and publication in national or
international journals. The D2P (data to policy) training initiative is
relatively new, and it teaches health workers how to apply 'decision analysis'
and develop policy briefs for policy makers: this includes description of a
problem and the available evidence, quantitative comparisons of policy options
that take into account predicted health and economic impacts, and political and
feasibility assessments. Policies adopted from evidence-based information
generated through the SORT IT and D2P approaches can be evaluated to assess their
impact, and the cycle repeated to identify and resolve new public health
problems. Ministries of Health could benefit from this twin-training approach to
make themselves 'data rich, information rich and action rich', and thereby use
routinely collected data in a synergistic manner to improve public health policy
making and health care delivery.
PMID- 29946519
TI - A systematic review of the effectiveness of smoking cessation interventions among
patients with tuberculosis.
AB - Smoking is a significant risk factor for morbidity and mortality, particularly
among patients with tuberculosis (TB). Although smoking cessation is recommended
by the World Health Organization and the International Union Against Tuberculosis
and Lung Disease, there has been no published evaluation of smoking cessation
interventions among people with TB. The purpose of this review was to synthesize
the evidence on interventions and suggest practice, research and policy
implications. A systematic review of the literature identified 14 peer-reviewed
studies describing 13 smoking cessation interventions between 2007 and 2017.
There were five randomized controlled trials, three non-randomized interventions,
and five prospective cohort studies. The primary types of interventions were
brief advice (n = 9), behavioral counseling (n = 4), medication (n = 3), and
community-based care (n = 3). A variety of health care workers (HCWs) implemented
interventions, from physicians, nurses, clinic staff, community health workers
(CHWs), as did family members. There was significant heterogeneity of design,
definition of smoking and smoking abstinence, and implementation, making
comparison across studies difficult. Although all smoking interventions increased
smoking cessation between 15% and 82%, many studies had a high risk for bias,
including six without a control group. The implementing personnel did not make a
large difference in cessation results, suggesting that national TB programs may
customize according to their needs and limitations. Family members may be
important supporters/advocates for cessation. Future research should standardize
definitions of smoking and cessation to allow comparisons across studies. Policy
makers should encourage collaboration between tobacco and TB initiatives and
develop smoking cessation measures to maximize results in low-resource settings.
PMID- 29946520
TI - Integration of tobacco cessation and tuberculosis management by NGOs in urban
India: a mixed-methods study.
AB - Setting and objectives: Tobacco use compromises tuberculosis (TB) treatment
outcomes. Tobacco cessation is beneficial to TB patients at the individual level
and from the perspective of a larger spectrum of non-communicable diseases
associated with tobacco use. We assessed feasibility, effectiveness and provider
perceptions on integrating brief tobacco cessation advice into routine TB care by
DOTS providers from 27 TB treatment centres run by three non-governmental
organisations (NGOs) in urban India. Design: A mixed-methods study (triangulation
design) involving analysis of programme data and semi-structured interviews
(quantitative) and thematic analysis of focus group discussions of TB treatment
providers (qualitative) regarding brief advice and cessation support provided to
self-reported tobacco users from August 2015 to July 2017. Results: All 27
centres initiated tobacco cessation. Of 2132 registered TB patients, 377 (18%)
were tobacco users, 333 (88%) of whom used smokeless tobacco. There was a
progressive drop in documentation of tobacco status at each visit, reaching
respectively 36% and 30% at the end of treatment for new and retreatment TB
patients. Seven-day point prevalence abstinence at 6 months was 32% among new and
15% among retreatment cases. Enablers for integration included NGO collaboration,
supervision and capacity building. Challenges included providers spending 15-45
min per patient (10 min recommended), multiple addictions, documentation load,
self-reporting and social normalisation of tobacco. Conclusions: Integration of
tobacco cessation into routine TB care in an urban NGO setting was feasible,
although without continued support, rigour in documentation declined. This should
be scaled up with special attention paid to tackling smokeless tobacco and
related operational challenges.
PMID- 29946521
TI - Delay and attrition before treatment initiation among MDR-TB patients in five
districts of Gujarat, India.
AB - Setting: Gujarat, a state in west India. Background: Although treatment
initiation has been improving among patients diagnosed with multidrug-resistant
tuberculosis (MDR-TB) in programme settings, it has still not reached 100%.
Objectives: To determine pre-treatment attrition (not initiated on treatment
within 6 months of diagnosis), delay in treatment initiation (>7 days from
diagnosis) and associated factors among MDR-TB patients diagnosed in 2014 in five
selected districts served by two genotypic drug susceptibility testing (DST)
facilities and a drug-resistant TB centre in Gujarat. Design: This was a
retrospective cohort study involving record review. Results: Among 257 MDR-TB
patients, pre-treatment attrition was seen in 20 (8%, 95%CI 5-12). Patients with
'follow-up sputum-positive' as their DST criterion and sputum smear microscopy
status 'unknown' at the time of referral for DST were less likely to be initiated
on treatment. The median delay to treatment initiation was 8 days (interquartile
range 6-13). Patients referred for DST from medical colleges were more likely to
face delays in treatment initiation. Conclusion: The Gujarat TB programme is
performing well in initiating laboratory-confirmed MDR-TB patients on treatment.
However, there is further scope for reducing delay.
PMID- 29946522
TI - Has TB CARE I sputum transport improved access to culture services for
retreatment tuberculosis patients in Zimbabwe?
AB - Setting: Retreatment tuberculosis (TB) patients in Zimbabwe are investigated
using microscopy, Xpert(r) MTB/RIF and culture + drug susceptibility testing
(CDST). TB CARE I, a sputum transport service using motorcycles, was introduced
to transport specimens between peripheral health facilities and laboratories,
including National Reference Laboratories (NRLs). Objectives: To compare access
to CDST and treatment outcomes among retreatment TB patients in facilities with
and those without TB CARE I support. Design: This was a retrospective cohort
study. Results: There were 187 patients from TB CARE I-supported facilities and
116 from non-TB CARE I facilities, with no difference in demographic
characteristics. Altogether, specimens from 22 (12%) retreatment TB patients had
successful CDST from TB CARE I facilities, which was not statistically
significantly different from non-supported facilities (n = 14, 12%; P = 0.94).
The median number of days from sputum collection to receipt at the NRL was lower
in TB CARE I facilities than in non-supported facilities (median 6, interquartile
range [IQR] 4-8 vs. median 8, IQR 6-13.5; P = 0.000). Favourable treatment
outcomes were documented in 65% of patients under TB CARE I, significantly more
than among patients in non-supported facilities (47%, P < 0.01). Conclusion: The
process of sputum specimen collection for CDST was not different between TB CARE
I and non-TB CARE I-supported health facilities, apart from a slightly shorter
time. Ways to improve the current system are discussed.
PMID- 29946524
TI - Scaling up electronic village registers for measuring vital statistics in rural
villages in Malawi.
AB - Setting: Eighty-three villages without electricity in Mtema Traditional
Authority, Lilongwe District, Malawi. Objectives: To describe 1) the expansion of
the electronic village register (EVR) to 83 villages in Mtema Traditional
Authority, 2) the challenges encountered and changes made to render the system
robust and user-friendly, 3) the value propositions developed to increase the
system's desirability, and 4) the results of the village register. Design:
Descriptive study. Results: After the deployment of the EVR in one village in
2013, the system was extended to 83 villages with modifications to render it more
robust and user-friendly. These changes included modifications to the power,
connectivity and work stations, better battery security and a single modular
electronics panel. Value propositions of the EVR for the village headmen included
daily postings of news/sports items and sockets for charging mobile phones and
lanterns. Of the 47 559 residents registered, 48% were male, 14% were aged 0-4
years, 43% were aged 15-44 years and 4% were aged ?65 years. Between 1 April 2016
and 31 March 2017, 976 births and 177 deaths were recorded. The total equipment
cost per village was US$2430. Conclusion: An electronic village birth and death
registration system can function in an area with no communication or electricity
infrastructure.
PMID- 29946523
TI - Integrating home HIV counselling and testing into household TB contact
investigation: a mixed-methods study.
AB - Setting: Community health workers (CHWs) increasingly deliver community-based
human immunodeficiency virus (HIV) counselling and testing (HCT) services. Less
is known about how this strategy performs when integrated with household
tuberculosis (TB) contact investigations. Objective: We conducted a prospective
mixed-methods study to evaluate the feasibility and quality of CHW-facilitated,
home-based HCT among household TB contacts. Design: CHWs visited households of
consenting TB patients to screen household contacts for TB and HIV. They
performed HIV testing using a serial enzyme-linked immunosorbent assay rapid
antibody testing algorithm. Laboratory technicians at health facilities re-tested
the samples and coordinated quarterly HIV panel testing for CHWs. We conducted
focus group discussions (FGDs) with CHWs on their experiences in carrying out
home-based HCT. Results: Of 114 household contacts who consented to and underwent
HIV testing by CHWs, 5 (4%) tested positive, 108 (95%) tested negative, and 1
(1%) had indeterminate results; 110 (96%) samples had adequate volume for re
testing. Overall agreement between CHWs and laboratory technicians was 99.1%
(kappa = 0.90, 95%CI 0.71-1.00, P < 0.0001). In FGDs, CHWs described context
specific social challenges to performing HCT in a household setting, but said
that their confidence grew with experience. Conclusion: Home-based HCT by CHWs
was feasible among household TB contacts and produced high-quality results.
Strategies to address social challenges are required to optimize yield.
PMID- 29946525
TI - Community-based integrated approach to changing women's family planning behaviour
in Pakistan, 2014-2016.
AB - Setting: Karachi, Pakistan. Objective: To assess the effectiveness of a community
based integrated approach in changing women's behaviour regarding contraceptive
use. Design: The Sukh Initiative is a multipronged approach with door-to-door
services using community health workers to provide quality family
planning/reproductive health services at both public and private facilities and a
24/7 family planning helpline service that provides youth skill-based education.
Methods: Retrospective pre- and post-intervention data using samples of 5140 and
3810 women, respectively. Results: The contraceptive prevalence rate increased by
10.7%, from 42.3% at baseline to 53.0% mid-intervention, with an increase in use
of modern contraceptive methods of 9.2%. A significant association was found
between door-to-door counselling and the use of contraceptive methods (OR 3.4,
95%CL 2.9-4.1) and access to public and private facilities for modern
contraceptives (OR 2.4, 95%CL 2.0-3.0). However, support group meetings and 24/7
helpline use did not show any association with use of contraceptive method.
Conclusion: The study helped to increase access to and choice of family planning
services through a community-based approach that successfully reduced unmet needs
and improved continuity in contraceptive use.
PMID- 29946526
TI - Implementation of an active, clinic-based child tuberculosis contact management
strategy in western Kenya.
AB - Tuberculosis (TB) is a leading cause of childhood mortality. Isoniazid preventive
therapy significantly reduces progression to TB disease. The World Health
Organization recommends that high TB burden countries conduct child contact
management (CCM) to identify exposed child contacts aged <5 years for screening
and appropriate treatment. An active, clinic-based CCM strategy incorporating
transport/screening reimbursement, monitoring and evaluation tools, and health
care worker education was implemented in western Kenya. Among 169 identified
child contacts aged <5 years, 146 (86%) underwent successful screening, of whom
43 (29%) were diagnosed with active TB. We describe our CCM strategy and its
potential for enhancing screening and treatment efforts.
PMID- 29946527
TI - Pre-diagnosis attrition in patients with presumptive MDR-TB in Bhopal, India,
2015: a follow-up study.
PMID- 29946528
TI - Pyridoxine for patients suffering from drug-susceptible tuberculosis in India.
PMID- 29946529
TI - Research priorities in non-communicable diseases in developing countries: time to
go beyond prevalence studies.
PMID- 29946530
TI - Expression of the Circadian Clock Gene BMAL1 Positively Correlates With Antitumor
Immunity and Patient Survival in Metastatic Melanoma.
AB - Introduction: Melanoma is the most lethal type of skin cancer, with increasing
incidence and mortality rates worldwide. Multiple studies have demonstrated a
link between cancer development/progression and circadian disruption; however,
the complex role of tumor-autonomous molecular clocks remains poorly understood.
With that in mind, we investigated the pathophysiological relevance of clock
genes expression in metastatic melanoma. Methods: We analyzed gene expression,
somatic mutation, and clinical data from 340 metastatic melanomas from The Cancer
Genome Atlas, as well as gene expression data from 234 normal skin samples from
genotype-tissue expression. Findings were confirmed in independent datasets.
Results: In melanomas, the expression of most clock genes was remarkably reduced
and displayed a disrupted pattern of co-expression compared to the normal skins,
indicating a dysfunctional circadian clock. Importantly, we demonstrate that the
expression of the clock gene aryl hydrocarbon receptor nuclear translocator-like
protein 1 (BMAL1) positively correlates with patient overall survival and with
the expression of T-cell activity and exhaustion markers in the tumor bulk.
Accordingly, high BMAL1 expression in pretreatment samples was significantly
associated with clinical benefit from immune checkpoint inhibitors. The robust
intratumoral T-cell infiltration/activation observed in patients with high BMAL1
expression was associated with a decreased expression of key DNA-repair enzymes,
and with an increased mutational/neoantigen load. Conclusion: Overall, our data
corroborate previous reports regarding the impact of BMAL1 expression on the
cellular DNA-repair capacity and indicate that alterations in the tumor
autonomous molecular clock could influence the cellular composition of the
surrounding microenvironment. Moreover, we revealed the potential of BMAL1 as a
clinically relevant prognostic factor and biomarker for T-cell-based
immunotherapies.
PMID- 29946531
TI - Preventing Breast Cancer-Related Lymphedema in High-Risk Patients: The Impact of
a Structured Surveillance Protocol Using Bioimpedance Spectroscopy.
AB - Purpose: We evaluated the impact of structured surveillance using bioimpedance
spectroscopy (BIS) to reduce the rate of chronic breast cancer-related lymphedema
(BCRL) in high-risk patients undergoing axillary lymph node dissection (ALND).
Methods: From April 2010 through November 2016, 93 patients who underwent ALND
were prospectively monitored with BIS using L-Dex. Intervention for an L-Dex
increase of >10 consisted of applying an over the counter (OTC) sleeve followed
by re-evaluation after 4 weeks. The utilization of complex decongestive
physiotherapy (CDP) represented a surrogate for chronic BCRL. Results: Median
follow-up was 24 months. 55% of patients received taxane-based chemotherapy, 24%
received some form of axillary irradiation (includes additional fields or high
tangents) and 66% had an elevated body mass index (BMI) with the median number of
nodes removed being 19. Overall, 75% of these patients had at least one
additional high-risk feature (taxane chemotherapy, axillary radiation, elevated
BMI), 48% had at least two, and 6% had all. Thirty-three patients (35.4%)
developed an elevated L-Dex score with only 10 (10.8%) requiring CDP (30.3% of
those undergoing treatment with sleeve). At last follow-up, only three patients
(3%) had unresolved BCRL. Conclusion: The results of this analysis support
previous data regarding prospective BCRL surveillance and early intervention
using BIS. With this approach, only 3% of patients have chronic BCRL.
PMID- 29946534
TI - StarSeeker: an automated tool for mature duplex microRNA sequence identification
based on secondary structure modeling of precursor molecule.
AB - Background: MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a
key role in gene regulation in both plants and animals. MicroRNA biogenesis
involves the enzymatic processing of a primary RNA transcript. The final step is
the production of a duplex molecule, often designated as miRNA:miRNA*, that will
yield a functional miRNA by separation of the two strands. This miRNA will be
incorporated into the RNA-induced silencing complex, which subsequently will bind
to its target mRNA in order to suppress its expression. The analysis of miRNAs is
still a developing area for computational biology with many open questions
regarding the structure and function of this important class of molecules. Here,
we present StarSeeker, a simple tool that outputs the putative miRNA* sequence
given the precursor and the mature sequences. Results: We evaluated StarSeeker
using a dataset consisting of all plant sequences available in miRBase (6992
precursor sequences and 8496 mature sequences). The program returned a total of
15,468 predicted miRNA* sequences. Of these, 2650 sequences were matched to
annotated miRNAs (~ 90% of the miRBase-annotated sequences). The remaining
predictions could not be verified, mainly because they do not comply with the
rule requiring the two overhanging nucleotides in the duplex molecule.
Conclusions: The expression pattern of some miRNAs in plants can be altered under
various abiotic stress conditions. Potential miRNA* molecules that do not degrade
can thus be detected and also discovered in high-throughput sequencing data,
helping us to understand their role in gene regulation.
PMID- 29946532
TI - Personalized Medicine in Malignant Melanoma: Towards Patient Tailored Treatment.
AB - Despite enormous international efforts, skin melanoma is still a major clinical
challenge. Melanoma takes a top place among the most common cancer types and it
has one of the most rapidly increasing incidences in many countries around the
world. Until recent years, there have been limited options for effective systemic
treatment of disseminated melanoma. However, lately, we have experienced a rapid
advancement in the understanding of the biology and molecular background of the
disease. This has led to new molecular classifications and the development of
more effective targeted therapies adapted to distinct melanoma subtypes. Not only
are these treatments more effective but they can be rationally prescribed to the
patients standing to benefit. As such, melanoma management has now become one of
the most developed for personalized medicine. The aim of the present paper is to
summarize the current knowledge on melanoma molecular classification, predictive
markers, combination therapies, as well as emerging new treatments.
PMID- 29946533
TI - Periostin: A Matricellular Protein With Multiple Functions in Cancer Development
and Progression.
AB - Tumor microenvironment is considered nowadays as one of the main players in
cancer development and progression. Tumor microenvironment is highly complex and
consists of non-tumor cells (i.e., cancer-associated fibroblast, endothelial
cells, or infiltrating leukocytes) and a large list of extracellular matrix
proteins and soluble factors. The way that microenvironment components interact
among them and with the tumor cells is very complex and only partially
understood. However, it is now clear that these interactions govern and modulate
many of the cancer hallmarks such as cell proliferation, the resistance to death,
the differentiation state of tumor cells, their ability to migrate and
metastasize, and the immune response against tumor cells. One of the
microenvironment components that have emerged in the last years with strength is
a heterogeneous group of multifaceted proteins grouped under the name of
matricellular proteins. Matricellular proteins are a family of non-structural
matrix proteins that regulate a variety of biological processes in normal and
pathological situations. Many components of this family such as periostin
(POSTN), osteopontin (SPP1), or the CNN family of proteins have been shown to
regulate key aspect of tumor biology, including proliferation, invasion, matrix
remodeling, and dissemination to pre-metastatic niches in distant organs.
Matricellular proteins can be produced by tumor cells themselves or by tumor
associated cells, and their synthesis can be affected by intrinsic and/or
extrinsic tumor cell factors. In this review, we will focus on the role of POSTN
in the development and progression of cancer. We will describe their functions in
normal tissues and the mechanisms involved in their regulation. We will analyze
the tumors in which their expression is altered and their usefulness as a
biomarker of tumor progression. Finally, we will speculate about future
directions for research and therapeutic approaches targeting POSTN.
PMID- 29946535
TI - Heterozygous COL4A3 Variants in Histologically Diagnosed Focal Segmental
Glomerulosclerosis.
AB - Introduction: Steroid-resistant nephrotic syndrome (SRNS) is one of the most
frequent causes for chronic kidney disease in childhood. In ~30% of these cases a
genetic cause can be identified. The histological finding in SRNS is often focal
segmental glomerulosclerosis (FSGS). In rare cases, however, pathogenic variants
in genes associated with Alport syndrome can be identified in patients with the
histological finding of FSGS. Materials and Methods: Clinical information was
collected out of clinical reports and medical history. Focused molecular genetic
analysis included sequencing of COL4A5 and COL4A3 in the index patient.
Segregation analysis of identified variants was performed in the parents and
children of the index patient. Results: The female index patient developed mild
proteinuria and microscopic hematuria in childhood (12 years of age). The
histological examination of the kidney biopsies performed at the age of 21, 28,
and 32 years showed findings partly compatible with FSGS. However,
immunosuppressive treatment of the index patient did not lead to a sufficient
reduction of in part nephrotic-range proteinuria. After the patient developed
hearing impairment at the age of 34 years and her daughter was diagnosed with
microscopic hematuria at the age of 6 years, re-examination of the index's kidney
biopsies by electron microscopy revealed textural changes of glomerular basement
membrane compatible with Alport syndrome. Molecular genetic analysis identified
two missense variants in COL4A3 in a compound heterozygous state with maternal
and paternal inheritance. One of them is a novel variant that was also found in
the 6 year old daughter of the index patient who presented with microscopic
hematuria. Discussion: We were able to show that a novel variant combined with a
previously described variant in compound heterozygous state resulted in a
phenotype that was histologically associated with FSGS. Molecular genetic
analysis therefore can be essential to solve difficult cases that show an unusual
appearance and therefore improve diagnostic accuracy. Additionally, unnecessary
and inefficient treatment with multiple side effects can be avoided.
PMID- 29946536
TI - Analysis of Radiopaque Gastrointestinal Foreign Bodies Expelled by Spontaneous
Passage in Children: A 15-Year Single-Center Study.
AB - Background: Most ingested foreign bodies (FBs) pass spontaneously through the
gastrointestinal (GI) tract, but only limited data on transit time are available.
We evaluated the relationship of FB size and shape with transit time. Methods: We
retrospectively reviewed medical records collected over 15 years (January 2001 to
December 2015) on pediatric patients with radiopaque FBs in the GI tract. We
categorized the FBs as regularly (round or spherical) or irregularly shaped
(ovoid, long, flake-like, or projecting) and measured their sizes
radiographically. The diameter of regularly shaped FBs and the length of
irregularly shaped FBs were correlated with transit time. Results: In total, 484
patients with GI FBs were surveyed, and 267 (55.1%) FBs were radiopaque. Among
the 267 radiopaque FBs, 88 (33.1%) required endoscopic removal and 7 (2.6%)
underwent surgical intervention. Eighty-seven patients with single FBs in the GI
tract for whom precise details of transit time were enrolled into the analysis of
transit time; their mean age was 3.48 +/- 2.21 years. Of the 87 FBs, 61 (70.1%)
were regularly shaped, and 26 (29.9%) were irregularly shaped. The diameter of
regularly shaped FBs was positively associated with transit time, as revealed by
Mann-Whitney U test; diameters >1.5 and >2 cm were significantly correlated with
longer transit times (both p = 0.003). A trend toward an increased transit time
for long irregularly shaped FBs was also apparent; the p-values for lengths of
1.5, 2, and 2.5 cm were 0.824, 0.153, and 0.055, respectively. Under receiver
operating characteristic (ROC) curve analysis, the optimal cutoff diameter for
regularly shaped FBs, and length for irregularly shaped FBs, to predict a transit
time of longer than 72 h were 1.95 and 2.25 cm, respectively. Conclusions: The
passage rate of ingested radiopaque FBs is 64.4%. Small FBs that have passed the
duodenal curve should be managed conservatively via clinical observation and
radiographic surveillance. Our results indicate that the larger an FB is, the
longer the transit time will be.
PMID- 29946538
TI - Synthesis, in-Vitro and in Silico Studies of Azo-Based Calix[4]arenes as
Antibacterial Agent and Neuraminidase Inhibitor: A New Look Into an Old Scaffold.
AB - Calixarene derivatives are reported as potential therapeutic agents. Azo
derivatives of calixarenes have not been given much consideration to explore
their biomedical applications. In the present study, some azo-based derivatives
of calix[4]arene were synthesized and characterized and their antibacterial and
antiviral potentials were studied. The mono azo products of sulphanilamide,
sulfaguanidine and 2-methyl-4-aminobenzoic acid showed good activity against
bacterial strains with minimum inhibition concentration values ranging from 0.97
to 62.5 MUg/mL. For mono azo products, the diazotized salt was applied as a
limiting reagent. The use of calix[4]arene and sodium acetate trihydrate in 1:3
(molar ratio) helped in partial substitution. Molecular docking was performed to
see the interaction of the designed compounds with two bacterial and one viral
(neuraminidase) receptor. Some of the derivatives showed good interaction with
the active site of bacterial and neuraminidase enzymes through hydrogen,
hydrophobic and pi-pi interactions, and could inhibit the activity of the
selected enzymes.
PMID- 29946537
TI - A Practical Method to Estimate the Resolving Power of a Chemical Sensor Array:
Application to Feature Selection.
AB - A methodology to calculate analytical figures of merit is not well established
for detection systems that are based on sensor arrays with low sensor
selectivity. In this work, we present a practical approach to estimate the
Resolving Power of a sensory system, considering non-linear sensors and
heteroscedastic sensor noise. We use the definition introduced by Shannon in the
field of communication theory to quantify the number of symbols in a noisy
environment, and its version adapted by Gardner and Barlett for chemical sensor
systems. Our method combines dimensionality reduction and the use of algorithms
to compute the convex hull of the empirical data to estimate the data volume in
the sensor response space. We validate our methodology with synthetic data and
with actual data captured with temperature-modulated MOX gas sensors. Unlike
other methodologies, our method does not require the intrinsic dimensionality of
the sensor response to be smaller than the dimensionality of the input space.
Moreover, our method circumvents the problem to obtain the sensitivity matrix,
which usually is not known. Hence, our method is able to successfully compute the
Resolving Power of actual chemical sensor arrays. We provide a relevant figure of
merit, and a methodology to calculate it, that was missing in the literature to
benchmark broad-response gas sensor arrays.
PMID- 29946539
TI - Droplet Fusion in Oil-in-Water Pickering Emulsions.
AB - We have formed compound droplets made of two or more drops of immiscible oils by
temporarily destabilizing Pickering oil-in-water emulsions. The emulsions used
are synergistically stabilized by mixtures of cationic surfactant and negatively
charged particles. They are highly sensitive to the concentration of surfactant
present in the emulsions. We took advantage of transient droplet coalescence
events that are triggered by reducing the surfactant concentration to fuse
together drops of immiscible oils. This study provides guidelines for designing
compound droplets by transient (or limited) coalescence in Pickering emulsions.
We show that the possible geometries of particle-stabilized compound drops are
determined by the interfacial tensions and relative volumes of the drops fused
together. The implications of our results for designing strategies to fabricate
multiphase drops are discussed.
PMID- 29946540
TI - High Efficient Visible-Light Photocatalytic Performance of Cu/ZnO/rGO
Nanocomposite for Decomposing of Aqueous Ammonia and Treatment of Domestic
Wastewater.
AB - Photocatalytic removal of ammonium-nitrogen ( NH4+ -N) from water using solar
energy is an approach of high interest and applicability due to the convenience
in application. ZnO has a great potential in photocatalytic decomposition of NH4+
-N and conversion of this nutrient to under visible light irradiations. However
the applicability of pristine ZnO though is limited due to its reduced capacity
to utilize light from natural light. Herein, we report a two-step ZnO-modified
strategy (Cu-doped ZnO nanoparticles, immobilized on reduced graphene oxide (rGO)
sheets) for the promotion of photocatalytic degradation of NH4+ -N under visible
light. UV-Vis spectra showed that the Cu/ZnO/rGO can be highly efficient in the
utilization of photons from the visible region. Hence, Cu/ZnO/rGO managed to
demonstrate adequate photocatalytic activity and effective NH4+ -N removal from
water under visible light compared to single ZnO. Specifically, up to 83.1% of
NH4+ -N (initial concentration 50 mg.L-1, catalyst dosage 2 g.L-1, pH 10) was
removed within 2 h retention time under Xe lamp irradiation. From the catalysis,
the major by-product was N2. The high ammonia degradation efficiency from the
ZnO/Cu/rGO is attributed to the improvement of the reactive oxygen species (ROSs)
production efficiency and the further activation of the interfacial catalytic
sites. This study also demonstrated that such nanocomposite is a recyclable
agent. Its NH4+ -N removal capacity remained effective even after five batch
cycles. In addition, Cu/ZnO/rGO was applied to treat real domestic wastewater,
and it was found that chemical oxygen demand (COD), total nitrogen (TN) and total
phosphorus (TP) removal efficiencies can reach 84.3, 80.7, and 90.3%,
respectively. Thus, Cu/ZnO/rGO in the presence of solar light can be a promising
photocatalyst in the field of wastewater treatment.
PMID- 29946541
TI - Capacity Increase Investigation of Cu2Se Electrode by Using Electrochemical
Impedance Spectroscopy.
AB - Cu2Se nanoflake arrays supported by Cu foams are synthesized by a facile
hydrothermal method in this study. The Cu2Se materials are directly used as an
anode for lithium ion batteries, which show superior cycle performance with
significant capacity increase. Combining with previous reports and scanning
electron microscope images after cycling, the capacity increase caused by the
reversible growth of a polymeric film is discussed. Electrochemical impedance
spectroscopy is used to test the reversible growth of the polymeric film. By
analyzing the three-dimensional Nyquist plots at different potentials during the
discharge/charge process, detailed electrochemical reaction information can be
obtained, which can further verify the reversible formation of a polymeric film
at low potential.
PMID- 29946542
TI - Commentary: Synthetic Addiction Extends the Productive Life Time of Engineered
Escherichia coli Populations.
PMID- 29946543
TI - Granular Carbon-Based Electrodes as Cathodes in Methane-Producing
Bioelectrochemical Systems.
AB - Methane-producing bioelectrochemical systems generate methane by using
microorganisms to reduce carbon dioxide at the cathode with external electricity
supply. This technology provides an innovative approach for renewable electricity
conversion and storage. Two key factors that need further attention are
production of methane at high rate, and stable performance under intermittent
electricity supply. To study these key factors, we have used two electrode
materials: granular activated carbon (GAC) and graphite granules (GG). Under
galvanostatic control, the biocathodes achieved methane production rates of
around 65 L CH4/m2catproj/d at 35 A/m2catproj, which is 3.8 times higher than
reported so far. We also operated all biocathodes with intermittent current
supply (time-ON/time-OFF: 4-2', 3-3', 2-4'). Current-to-methane efficiencies of
all biocathodes were stable around 60% at 10 A/m2catproj and slightly decreased
with increasing OFF time at 35 A/m2catproj, but original performance of all
biocathodes was recovered soon after intermittent operation. Interestingly, the
GAC biocathodes had a lower overpotential than the GG biocathodes, with methane
generation occurring at -0.52 V vs. Ag/AgCl for GAC and at -0.92 V for GG at a
current density of 10 A/m2catproj. 16S rRNA gene analysis showed that
Methanobacterium was the dominant methanogen and that the GAC biocathodes
experienced a higher abundance of proteobacteria than the GG biocathodes. Both
cathode materials show promise for the practical application of methane-producing
BESs.
PMID- 29946545
TI - Retrospective Study of Reported Adverse Events Due to Complementary Health
Products in Singapore From 2010 to 2016.
AB - The objective of this study is to collate and analyse adverse event reports
associated with the use of complementary health products (CHP) submitted to the
Health Sciences Authority (HSA) of Singapore for the period 2010-2016 to identify
various trends and signals for pharmacovigilance purposes. A total of 147,215
adverse event reports suspected to be associated with pharmaceutical products and
CHP were received by HSA between 2010 and 2016. Of these, 143,191 (97.3%) were
associated with chemical drugs, 1,807 (1.2%) with vaccines, 1,324 (0.9%) with
biological drugs (biologics), and 893 (0.6%) with CHP. The number of adverse
event reports associated with Chinese Proprietary Medicine, other complementary
medicine and health supplements are presented. Eight hundred and ninety three
adverse event reports associated with CHP in the 7-year period have been
successfully collated and analyzed. In agreement with other studies, adverse
events related to the "skin and appendages disorders" were the most commonly
reported. Most of the cases involved dermal allergies (e.g., rashes) associated
with the use of glucosamine products and most of the adulterated products were
associated with the illegal addition of undeclared drugs for pain relief.
Dexamethasone, chlorpheniramine, and piroxicam were the most common adulterants
detected. Reporting suspected adverse events is strongly encouraged even if the
causality is not confirmed because any signs of clustering will allow rapid
regulatory actions to be taken. The findings from this study help to create
greater awareness on the health risks, albeit low, when consuming CHP and
dispelling the common misconception that "natural" means "safe." In particular,
healthcare professionals and the general public should be aware of potential
adulteration of CHP. The analysis of spontaneously reported adverse events is an
important surveillance system in monitoring the safety of CHP and helps in the
understanding of the risk associated with the use of such products. Greater
collaboration and communication between healthcare professionals, regulators,
patients, manufacturers, researchers, and the general public are important to
ensure the quality and safety of CHP.
PMID- 29946546
TI - The Impact of Antidepressant Therapy on Glycemic Control in Canadian Primary Care
Patients With Diabetes Mellitus.
AB - Context: Depression is common in people with diabetes and is associated with poor
glycemic control. Evidence suggests that certain antidepressants (AD) increase
the risk of poor control. Few population-based studies have examined the impact
of individual ADs on glycemic control. This study's objective is to measure the
impact of Citalopram, Amitriptyline, Venlafaxine, Trazodone and Escitalopram on
glycated hemoglobin (HbA1c) in Canadian primary care patients with diabetes.
Methods: A retrospective study of electronic medical records (EMR) from 115
primary care practices across Canada was undertaken. Data were obtained from the
Canadian Primary Care Sentinel Surveillance Network (CPCSSN). The sample
population comprised 1,084 diabetic patients with 1,127 prescriptions of one of
the five selected ADs and with baseline and post-exposure HbA1c measurements.
Generalized linear mixed models were computed to estimate the effect of the ADs
on HbA1c. Results: Mean HbA1c ratios for Amitriptyline, Venlafaxine, Trazodone
and Escitalopram were all numerically lower than Citalopram. The confidence
intervals included the minimum detectable effect, however the differences were
not statistically significant. The lowest clinically relevant HbA1c ratios,
relative to Citalopram, were found in patients prescribed Trazodone and
Escitalopram. Accounting for the prescription of Trazodone for indications other
than depression, this research suggests that Escitalopram may be safer than
Citalopram for people with diabetes and depression, in terms of its effect on
blood glucose. Conclusion: This study can inform future research examining the
relationship between ADs and blood glucose and provides insight into the
limitations pertaining to the use of health data in health research. Future
research should seek to control for, across multiple time points: depression
symptoms, depression severity, depression duration, weight, diabetes medication,
tobacco and alcohol consumption and other medications with a known impact on
blood glucose.
PMID- 29946547
TI - Ligand-Induced Variations in Structural and Dynamical Properties Within an Enzyme
Superfamily.
AB - Enzyme catalysis is a complex process involving several steps along the reaction
coordinates, including substrate recognition and binding, chemical
transformation, and product release. Evidence continues to emerge linking the
functional and evolutionary role of conformational exchange processes in optimal
catalytic activity. Ligand binding changes the conformational landscape of
enzymes, inducing long-range conformational rearrangements. Using functionally
distinct members of the pancreatic ribonuclease superfamily as a model system, we
characterized the structural and conformational changes associated with the
binding of two mononucleotide ligands. By combining NMR chemical shift titration
experiments with the chemical shift projection analysis (CHESPA) and relaxation
dispersion experiments, we show that biologically distinct members of the RNase
superfamily display discrete chemical shift perturbations upon ligand binding
that are not conserved even in structurally related members. Amino acid networks
exhibiting coordinated chemical shift displacements upon binding of the two
ligands are unique to each of the RNases analyzed. Our results reveal the
contribution of conformational rearrangements to the observed chemical shift
perturbations. These observations provide important insights into the
contribution of the different ligand binding specificities and effects of
conformational exchange on the observed perturbations associated with ligand
binding for functionally diverse members of the pancreatic RNase superfamily.
PMID- 29946544
TI - Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor
Microenvironment.
AB - Historically, the link between chronic inflammation and cancer has long been
speculated. Only more recently, pre-clinical and epidemiologic data as well as
clinical evidence all point to the role of the tumor microenvironment as
inextricably connected to the neoplastic process. The tumor microenvironment
(TME), a complex mix of vasculature, inflammatory cells, and stromal cells is the
essential "soil" helping to modulate tumor potential. Increasingly, evidence
suggests that chronic inflammation modifies the tumor microenvironment, via a
host of mechanisms, including the production of cytokines, pro-inflammatory
mediators, angiogenesis, and tissue remodeling. Inflammation can be triggered by
a variety of different pressures, such as carcinogen exposure, immune
dysfunction, dietary habits, and obesity, as well as genetic alterations leading
to oncogene activation or loss of tumor suppressors. In this review, we examine
the concept of the tumor microenvironment as related to both extrinsic and
intrinsic stimuli that promote chronic inflammation and in turn tumorigenesis.
Understanding the common pathways inherent in an inflammatory response and the
tumor microenvironment may shed light on new therapies for both primary and
metastatic disease. The concept of personalized medicine has pushed the field of
oncology to drill down on the genetic changes of a cancer, in the hopes of
identifying individually targeted agents. Given the complexities of the tumor
microenvironment, it is clear that effective oncologic therapies will necessitate
targeting not only the cancer cells, but their dynamic relationship to the tumor
microenvironment as well.
PMID- 29946548
TI - Biochemical Properties of Human D-amino Acid Oxidase Variants and Their Potential
Significance in Pathologies.
AB - The stereoselective flavoenzyme D-amino acid oxidase (DAAO) catalyzes the
oxidative deamination of neutral and polar D-amino acids producing the
corresponding alpha-keto acids, ammonia, and hydrogen peroxide. Despite its
peculiar and atypical substrates, DAAO is widespread expressed in most eukaryotic
organisms. In mammals (and humans in particular), DAAO is involved in relevant
physiological processes ranging from D-amino acid detoxification in kidney to
neurotransmission in the central nervous system, where DAAO is responsible of the
catabolism of D-serine, a key endogenous co-agonist of N-methyl-D-aspartate
receptors. Recently, structural and functional studies have brought to the fore
the distinctive biochemical properties of human DAAO (hDAAO). It appears to have
evolved to allow a strict regulation of its activity, so that the enzyme can
finely control the concentration of substrates (such as D-serine in the brain)
without yielding to an excessive production of hydrogen peroxide, a potentially
toxic reactive oxygen species (ROS). Indeed, dysregulation in D-serine
metabolism, likely resulting from altered levels of hDAAO expression and
activity, has been implicated in several pathologies, ranging from renal disease
to neurological, neurodegenerative, and psychiatric disorders. Only one mutation
in DAO gene was unequivocally associated to a human disease. However, several
single nucleotide polymorphisms (SNPs) are reported in the database and the
biochemical characterization of the corresponding recombinant hDAAO variants is
of great interest for investigating the effect of mutations. Here we reviewed
recently published data focusing on the modifications of the structural and
functional properties induced by amino acid substitutions encoded by confirmed
SNPs and on their effect on D-serine cellular levels. The potential significance
of the different hDAAO variants in human pathologies will be also discussed.
PMID- 29946550
TI - The Regulation of Insulin-Stimulated Cardiac Glucose Transport via Protein
Acetylation.
AB - Cellular catabolism is the cell capacity to generate energy from various
substrates to sustain its function. To optimize this energy production, cells are
able to switch between various metabolic pathways in accordance to substrate
availability via a modulation of several regulatory enzymes. This metabolic
flexibility is essential for the healthy heart, an organ requiring large
quantities of ATP to sustain its contractile function. In type 2 diabetes, excess
of non-glucidic nutrients such as fatty acids, branched-chain amino-acids, or
ketones bodies, induces cardiac metabolic inflexibility. It is characterized by a
preferential use of these alternative substrates to the detriment of glucose,
this participating in cardiomyocytes dysfunction and development of diabetic
cardiomyopathy. Identification of the molecular mechanisms leading to this
metabolic inflexibility have been scrutinized during last decades. In 1963,
Randle demonstrated that accumulation of some metabolites from fatty acid
metabolism are able to allosterically inhibit regulatory steps of glucose
metabolism leading to a preferential use of fatty acids by the heart.
Nevertheless, this model does not fully recapitulate observations made in
diabetic patients, calling for a more complex model. A new piece of the puzzle
emerges from recent evidences gathered from different laboratories showing that
metabolism of the non-glucidic substrates induces an increase in acetylation
levels of proteins which is concomitant to the perturbation of glucose transport.
The purpose of the present review is to gather, in a synthetic model, the
different evidences that demonstrate the role of acetylation in the inhibition of
the insulin-stimulated glucose uptake in cardiac muscle.
PMID- 29946549
TI - The BCR-ABL1 Inhibitors Imatinib and Ponatinib Decrease Plasma Cholesterol and
Atherosclerosis, and Nilotinib and Ponatinib Activate Coagulation in a
Translational Mouse Model.
AB - Treatment with the second and third generation BCR-ABL1 tyrosine kinase
inhibitors (TKIs) increases cardiovascular risk in chronic myeloid leukemia (CML)
patients. We investigated the vascular adverse effects of three generations of
TKIs in a translational model for atherosclerosis, the APOE*3Leiden.CETP mouse.
Mice were treated for sixteen weeks with imatinib (150 mg/kg BID), nilotinib (10
and 30 mg/kg QD) or ponatinib (3 and 10 mg/kg QD), giving similar drug exposures
as in CML-patients. Cardiovascular risk factors were analyzed longitudinally, and
histopathological analysis of atherosclerosis and transcriptome analysis of the
liver was performed. Imatinib and ponatinib decreased plasma cholesterol
(imatinib, -69%, p < 0.001; ponatinib 3 mg/kg, -37%, p < 0.001; ponatinib 10
mg/kg-44%, p < 0.001) and atherosclerotic lesion area (imatinib, -78%, p < 0.001;
ponatinib 3 mg/kg, -52%, p = 0.002; ponatinib 10 mg/kg, -48%, p = 0.006), which
were not affected by nilotinib. In addition, imatinib increased plaque stability.
Gene expression and pathway analysis demonstrated that ponatinib enhanced the
mRNA expression of coagulation factors of both the contact activation (intrinsic)
and tissue factor (extrinsic) pathways. In line with this, ponatinib enhanced
plasma levels of FVII, whereas nilotinib increased plasma FVIIa activity. While
imatinib showed a beneficial cardiovascular risk profile, nilotinib and ponatinib
increased the cardiovascular risk through induction of a pro-thrombotic state.
PMID- 29946551
TI - Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of
GSK-3 Activity.
AB - Intramuscular fat is important in large animal livestock species in regard to
meat quality and in humans is of clinical significance in particular in relation
to insulin resistance. The canonical Wnt signalling pathway has been implicated
at a whole body level in regulating relative levels of adiposity versus lean body
mass. Previously we have shown that pig muscle cells can undergo adipogenic
differentiation to a degree that is dependent upon the specific muscle source. In
this work we examine the role of the canonical Wnt pathway which acts through
inactivation of glycogen synthase kinase-3 (GSK-3) in the regulation of
adipogenic differentiation in muscle cells derived from the pig semimembranosus
muscle. The application of lithium chloride to muscle derived cells significantly
increased the phosphorylation of GSK-3beta and thus inhibited its activity thus
mimicking Wnt signaling. This was associated with a significant decrease in the
expression of the adipogenic transcription factor PPARgamma and an almost
complete inhibition of adipogenesis in the cells. The data also suggest that GSK
3alpha plays, at most, a small role in this process. Studies in vivo have
suggested that the Wnt pathway is a major regulator of whole body adiposity. In
this study we have shown that the ability of cells derived from porcine skeletal
muscle to differentiate along an adipogenic lineage, in vitro, is severely
impaired by mimicking the action of this pathway. This was done by inactivation
of GSK-3beta by the use of Lithium Chloride.
PMID- 29946552
TI - Periparturient Behavior and Physiology: Further Insight Into the Farrowing
Process for Primiparous and Multiparous Sows.
AB - Giving birth is a critical time for many species and is often the most painful
event ever experienced by females. In domestic species, like the pig, pain
associated with parturition represents a potential welfare concern, and the
consequences of pain can cause economic losses (e.g., by indirectly contributing
to piglet mortality as pain could slow post-farrowing recovery, reduce food and
water intake, reducing milk let-down). This study investigated pain assessment
and its management in primiparous (gilts) and multiparous (sows) breeding pigs,
including the provision of a non-steroidal anti-inflammatory drug (NSAID) post
parturition. Individuals were randomly allocated to receive the NSAID ketoprofen
(3 mg/kg bodyweight) (n = 11 gilts, 16 sows) or the equivalent volume of saline
(n = 13 gilts, 16 sows) by intramuscular injection 1.5 h after the birth of the
last piglet. Data collected included putative behavioral indicators of pain (back
leg forward, tremble, back arch), salivary cortisol concentrations pre-farrowing
and up to 7 days post-injection. In addition, post-partum biomarkers of
inflammation, including the acute phase protein C-reactive protein (CRP) and 3
porcine cytokines [interleukin-1 beta (IL1 beta), interleukin-6 (IL6), and tumor
necrosis factor alpha (TNF alpha)] were measured in plasma collected 6 h
following the injection. Behaviors were analyzed using generalized linear mixed
models, and physiological variables with linear mixed models. No difference in
putative pain behaviors, salivary cortisol, CRP, or cytokines were found between
individuals treated with ketoprofen or those administered the saline control.
However, there were some differences between gilts and sows, as sows exhibited
more putative pain behavior than gilts, had higher salivary cortisol on the day
of farrowing and had higher plasma TNF alpha. Conversely, gilts had higher
salivary cortisol than sows on day 3 post-farrowing and had higher CRP. This
indicates that, like human females, multiparous sows experience more pain from
uterine activity following birth than primiparas. This study provides useful
information for developing management practices relating to post-farrowing care
for breeding pigs.
PMID- 29946553
TI - Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus
Detections Among Patients Hospitalized With Community-Acquired Pneumonia.
AB - Background: Real-time polymerase chain reaction (PCR) on respiratory specimens
and serology on paired blood specimens are used to determine the etiology of
respiratory illnesses for research studies. However, convalescent serology is
often not collected. We used multiple imputation to assign values for missing
serology results to estimate virus-specific prevalence among pediatric and adult
community-acquired pneumonia hospitalizations using data from an active
population-based surveillance study. Methods: Presence of adenoviruses, human
metapneumovirus, influenza viruses, parainfluenza virus types 1-3, and
respiratory syncytial virus was defined by positive PCR on
nasopharyngeal/oropharyngeal specimens or a 4-fold rise in paired serology. We
performed multiple imputation by developing a multivariable regression model for
each virus using data from patients with available serology results. We
calculated absolute and relative differences in the proportion of each virus
detected comparing the imputed to observed (nonimputed) results. Results: Among
2222 children and 2259 adults, 98.8% and 99.5% had nasopharyngeal/oropharyngeal
specimens and 43.2% and 37.5% had paired serum specimens, respectively. Imputed
results increased viral etiology assignments by an absolute difference of 1.6%
4.4% and 0.8%-2.8% in children and adults, respectively; relative differences
were 1.1-3.0 times higher. Conclusions: Multiple imputation can be used when
serology results are missing, to refine virus-specific prevalence estimates, and
these will likely increase estimates.
PMID- 29946554
TI - Binimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to
chemotherapy and hormonal treatment.
AB - Background: Management of advanced/recurrent low-grade serous ovarian carcinoma
(LGOSC) is often challenging. Effective treatment options remain limited for
hormone and chemotherapy-resistant LGSOC.CASE: A 65-year-old woman with recurrent
widespread LGSOC harboring the KRAS-G12 V hotspot mutation experienced a dramatic
clinical response to Binimetinib (MEK162), a mitogen-activated protein kinase
(MEK) inhibitor, after failing multiple chemotherapy and hormonal treatments. An
81% reduction of target lesions by RECIST 1.1 over 31 months of response duration
was confirmed with serial CT scans. Episodes of drug-related toxicity
(pneumonitis) easily resolved without sequelae with the use of oral steroids.
Conclusion: Binimetinib may present a new treatment option for hormone- and
chemotherapy-resistant LGSOC harboring KRAS mutations.
PMID- 29946555
TI - Atherosclerosis as an inflammatory disease: Doubts? No more.
PMID- 29946556
TI - Association between the ratio of anti-angiogenic isoform of VEGF-A to total VEGF
A and adverse clinical outcomes in patients after acute myocardial infarction.
AB - Background: Vascular endothelial growth factor-A (VEGF-A) promotes
neovascularization and is attracting considerable attention as a remarkable risk
factor in patients after acute myocardial infarction (AMI). In contrast, the
association between VEGF-A165b, which is the main anti-angiogenic isoform of VEGF
A, and adverse clinical outcomes after AMI remains unclear. The present study
aimed to investigate the association between serum VEGF-A165b and major adverse
cardiac and cerebrovascular events (MACCEs) after percutaneous coronary
intervention (PCI) for AMI. Methods: We evaluated 23 patients with AMI who
underwent primary percutaneous coronary intervention. VEGF-A and VEGF-A165b
levels were measured on admission (day 1) and at days 3, 7, and 30 after PCI.
Results: The levels of total VEGF-A tended to be lower, while the ratio of VEGF
A165b to total VEGF-A tended to be higher in patients with MACCEs than in those
without. The patients with a high ratio of VEGF-A165b to total VEGF-A had a
significantly higher risk of MACCEs using the cut-off values for MACCEs at day 30
after PCI (0.87 vs. 0.25, log-rank test, p = 0.0058). Conclusion: The assessment
of VEGF-A165b combined with VEGF-A may be a valuable screening tool for
predicting MACCEs in clinical practice.
PMID- 29946557
TI - Changes in contractility determine coronary haemodynamics in dyssynchronous left
ventricular heart failure, not vice versa.
AB - Background: Biventricular pacing has been shown to increase both cardiac
contractility and coronary flow acutely but the causal relationship is unclear.
We hypothesised that changes in coronary flow are secondary to changes in cardiac
contractility. We sought to examine this relationship by modulating coronary flow
and cardiac contractility. Methods: Contractility and lusitropy were altered by
varying the location of pacing in 8 patients. Coronary autoregulation was
transiently disabled with intracoronary adenosine. Simultaneous coronary flow
velocity, coronary pressure and left ventricular pressure data were measured in
the different pacing settings with and without hyperaemia and wave intensity
analysis performed. Results: Multisite pacing was effective at altering left
ventricular contractility and lusitropy (pos. dp/dtmax -13% to +10% and neg.
dp/dtmax -15% to +17% compared to baseline). Intracoronary adenosine decreased
microvascular resistance (362.5 mm Hg/s/m to 156.7 mm Hg/s/m, p < 0.001) and
increased LAD flow velocity (22 cm/s vs 45 cm/s, p < 0.001) but did not acutely
change contractility or lusitropy. The magnitude of the dominant accelerating
wave, the Backward Expansion Wave, was proportional to the degree of
contractility as well as lusitropy (r = 0.47, p < 0.01 and r = -0.50, p < 0.01).
Perfusion efficiency (the proportion of accelerating waves) increased at
hyperaemia (76% rest vs 81% hyperaemia, p = 0.04). Perfusion efficiency
correlated with contractility and lusitropy at rest (r = 0.43 & -0.50
respectively, p = 0.01) and hyperaemia (r = 0.59 & -0.6, p < 0.01). Conclusions:
Acutely increasing coronary flow with adenosine in patients with systolic heart
failure does not increase contractility. Changes in coronary flow with
biventricular pacing are likely to be a consequence of enhanced cardiac
contractility from resynchronization and not vice versa.
PMID- 29946558
TI - Left ventricular scar and the acute hemodynamic effects of multivein and
multipolar pacing in cardiac resynchronization.
AB - Background: We sought to determine whether presence, amount and distribution of
scar impacts the degree of acute hemodynamic response (AHR) with multisite
pacing.Multi-vein pacing (MVP) or multipolar pacing (MPP) with a multi-electrode
left ventricular (LV) lead may offer benefits over conventional biventricular
pacing in patients with myocardial scar. Methods: In this multi-center study left
bundle branch block patients underwent an hemodynamic pacing study measuring LV
dP/dtmax. Patients had cardiac magnetic resonance scar imaging to assess the
effect of scar presence, amount and distribution on AHR. Results: 24 patients
(QRS 171 +/- 20 ms) completed the study (83% male). An ischemic etiology was
present in 58% and the mean scar volume was 6.0 +/- 7.0%. Overall discounting
scar, MPP and MVP showed no significant AHR increase compared to an optimized
"best BiV" (BestBiV) site. In a minority of patients (6/24) receiver-operator
characteristic analysis of scar volume (cut off 8.48%) predicted a small AHR
improvement with MPP (sensitivity 83%, specificity 94%) but not MVP. Patients
with scar volume > 8.48% had a MPP-BestBiV of 3 +/- 6.3% vs. -6.4 +/- 7.7% for
those below the cutoff. There was a significant correlation between the
difference in AHR and scar volume for MPP-BestBiV (R = 0.49, p = 0.02) but not
MVP-BestBiV(R = 0.111, p = 0.62). The multielectrode lead positioned in scar
predicted MPP AHR improvement (p = 0.04). Conclusions: Multisite pacing with MPP
and MVP shows no AHR benefit in all-comers compared to optimized BestBiV pacing.
There was a minority of patients with significant scar volume in relation to the
LV site that exhibited a small AHR improvement with MPP.(Study identifier
NCT01883141).
PMID- 29946559
TI - The long-term efficacy of concomitant maze IV surgery in patients with atrial
fibrillation.
AB - Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia, and
associated with increased risk of morbidity and mortality. AF surgery is widely
used for rhythm control of AF, but previous studies have shown varying results.
This study sought to investigate the long-term efficacy of concomitant maze IV
(CMIV) surgery in an unselected AF population and identify predictors of late AF
recurrence. Methods: In total 144 consecutive patients, who underwent CMIV
between January 2006 and December 2010 were enrolled. By data from electronic
medical records, registers, and rhythm prints, late AF recurrences and heart
rhythm at latest follow-up were retrospectively registered. All patients still
alive were invited to an ambulant follow-up to update rhythm status. Results:
During a median (IQR) follow-up of 7.39 (2.67) years, 114 (79.2%) patients had
recurrence. The cumulative incidence of sinus rhythm (SR) without antiarrhythmic
drugs (AADs) was 52.3% after 1 year. Long-term results after 2, 5 and 7 years
were 47.9%, 32.6% and 25.1%, respectively. At latest follow-up 34.7% were in SR
off AADs. No difference in 10-year event-free survival stratified by recurrence
were found (p = 0.678). Contrary, time to death (5.40 vs. 3.43 years, p = 0.004)
revealed death as competing risk event. The Fine-Gray model identified
preoperative sustained AF (SAF) (SHR 3.54, 95%CI [2.35;5.32], p < 0.001), AF
duration (1.08, [1.05;1.11], p < 0.001), and postoperative atrial tachyarrhythmia
(ATA) (2.29, [1.21;4.35], p = 0.011) as predictors. Conclusion: CMIV in the
present cohort provided limited long-term success in obtaining SR. SAF, longer AF
duration, and postoperative ATA were associated with late AF recurrence.
PMID- 29946561
TI - Low-frequency and low-intensity ultrasound increases cardiac parasympathetic
neural activity and decreases clinic hypertension in elderly hypertensive
subjects with type 2 diabetes.
AB - Background: The aims of the present study were to determine the effects of an
ultrasound irradiation on clinic hypertension and the heart rate variability in
elderly hypertensive subjects with type 2 diabetes. Methods: We examined the
effects of ultrasound (800 kHz, 25 mW/cm2) applied to the forearm for 10 min on
the autonomic nerve activity and the difference between BP at home and at a
clinic visit in Japanese subjects with type 2 diabetes and hypertension. Results:
In 108 subjects who displayed systolic BP (SBP) >140 mm Hg at a clinic visit, 75
subjects (69%) had a mean SBP <135 mm Hg at home and 33 subjects (31%) had a mean
SBP >135 mm Hg at home in the morning for 14 days. SBP, pulse rate, and pulse
pressure in the ultrasound treatment group were significantly lower than the
baseline values in these hypertensive subjects with type 2 diabetes, and lower
than those of placebo controls independently of SBP at home. In 31 subjects who
displayed systolic BP >140 mm Hg at a clinic, standard deviation of all RR
intervals and the root mean square of successive differences were significantly
higher in the ultrasound treatment group than the baseline values in these
hypertensive subjects with type 2 diabetes, and lower than those of placebo
controls. Conclusions: The ultrasound treatment increases the cardiac
parasympathetic neural activity and decreases the differences between SBP at home
and at a clinic visit in elderly hypertensive subjects with type 2 diabetes.
PMID- 29946560
TI - Effect of cardiac rehabilitation on the renal function in chronic kidney disease
Analysis using serum cystatin-C based glomerular filtration rate.
AB - Background: Whether an individually determined appropriate level of cardiac
rehabilitation (CR) has a favorable effect on the renal function still remains
unclarified. The aim of this study was to confirm the effect of CR on the
estimated glomerular filtration rate (eGFR) using cystatin C, which is known to
be unaffected by physical exercise. Methods: The study population was comprised
of 86 patients (61 males; average age 74 y/o) with a lower-moderate level of
chronic kidney disease (CKD) who was admitted to our hospital for treatment of
cardiovascular disease (CVD) and who participated in our 3-month CR program. The
exercise capacity was assessed by cardiopulmonary exercise testing (CPX) and the
eGFR was measured by a formula based on the serum cystatin C concentration
(eGFRcys) in each patient both at the beginning and end of the CR. Results: In
the CVD patients with CKD, both the peak oxygen uptake (VO2) and peak work rate
(WR) improved significantly after CR (15.0 +/- 3 to 15.8 +/- 3 ml/min/kg, p =
0.002. 65.5 +/- 21 to 70.2 +/- 25 W, p = 0.001). Regarding the renal function,
the eGFRcys improved (45.2 +/- 11 to 47.3 +/- 13 ml/min/1.73 m2, p = 0.023),
however, the eGFR assessed by the serum creatinine (eGFRcr) did not improve after
CR (45.1 +/- 12 to 44.9 +/- 13 ml/min/1.73 m2, p = 0.834). Conclusions: In CVD
patients, a novel CR program significantly improved the exercise capacity.
Further, CR was shown to have a favorable effect on the renal function when it
was estimated by the eGFRcys.
PMID- 29946562
TI - The sternal wire code; Solving the problem of missing coronary artery bypass
graft records during cardiac catheterization.
AB - Background: The sternal wire code records details of coronary artery bypass
surgery (CABG) inside patients, based on the orientation of wires used for
sternal closure. Visible on X-ray, the code overcomes the problem of missing
graft-notes needed before repeat angiography. We determined (i) the potential
value (ii) acceptability and (iii) accuracy of the code in practice. Methods: (i)
Consecutive coronary angiogram reports (2015-2016 Barts, London) were reviewed to
identify patients with previous CABG and those with and without graft-notes
before angiography. (ii) UK surgeons were surveyed on whether they would insert
the code during CABG. (iii) A clinician, blinded to operative details,
interpreted 16 post-CABG X-rays, 8 with the code and 8 without. Results: (i) Of
6483 angiography patients, 559 had previous CABG (9.2% (8.5-10%)). Graft-notes
were missing in 91/559 (15.1% (12-18%)); almost all (88/91) among patients with
acute myocardial infarction. (ii) In the survey, 66/71surgeons (93% (84-98%))
were willing to use the code. (iii) In the accuracy test, all coded X-rays were
identified and 28/28 grafts correctly interpreted (p < 0.001). Conclusions: About
1 in 6 patients with previous CABG, who require emergency coronary angiography,
undergo this procedure without graft-notes and would benefit from the sternal
wire code which appears clinically acceptable and accurate.
PMID- 29946563
TI - Junior medical student performed focused cardiac ultrasound after brief training
to detect significant valvular heart disease.
AB - Background: Focused cardiac ultrasound (FOCUS) examination using a portable
device is increasingly used for bedside diagnosis of cardiovascular diseases.
This is a 4-week pilot project aiming to teach medical students to perform FOCUS
to detect valvular heart lesions. Methods: Patients undergoing routine
transthoracic echocardiography (TTE) were recruited by third year medical
students who performed physical examination (PE) and FOCUS after 6-hour training
to detect significant (moderate-to-severe) valvular lesions. Performance of FOCUS
and PE was compared to TTE as reference using kappa statistics. Results: 10
medical students performed 212 PE and FOCUS on 107 patients with mean age 63.7 +/
14.9 years. TTE detected 126 significant valvular lesions of which FOCUS
correctly identified 54 lesions (kappa = 0.45) compared to 32 lesions by PE
(kappa = 0.28, p < 0.01). FOCUS was better than PE in identifying mitral stenosis
(kappa = 0.51 vs. 0.17), aortic stenosis (kappa = 0.45 vs. 0.16) and tricuspid
regurgitation (kappa = 0.39 vs. 0.09, all p < 0.01). Students became more
proficient in performing FOCUS examination with time. Conclusions: Teaching
junior medical students to perform and interpret FOCUS was feasible after brief
training and better than PE in detecting significant valvular lesions. Further
studies are warranted to determine the utility of incorporating this new
technology into mainstream medical training.
PMID- 29946564
TI - Changes in coronary atherosclerosis, composition, and fractional flow reserve
evaluated by coronary computed tomography angiography in patients with type 2
diabetes.
AB - Background: The use of coronary computed tomography angiography (CCTA) for
noninvasive anatomic detection of coronary artery disease is increasing.
Recently, fractional flow reserve (FFR) assessment using routinely acquired CCTA
datasets (FFRCT) has been developed. However, there are no reports about changes
in coronary atherosclerosis, composition, and FFRCT in patients with type 2
diabetes. Methods: This prospective, multicenter, observational trial evaluated
changes in coronary atherosclerosis after alogliptin therapy in patients with
type 2 diabetes. Fifty-one patients with type 2 diabetes who underwent CCTA
examination and having intermediate coronary artery stenosis were treated with 25
mg of alogliptin. After 48 weeks, CCTA examination was repeated. The primary
endpoint was changes in FFRCT, and the secondary endpoint was changes in total
atheroma volume (TAV) from the baseline to the 48-week follow-up. Results: The
FFRCT decreased from the baseline to follow-up, but not significantly. A
significant increase in TAV (from 658.5 mm3 to 668.9 mm3, p = 0.048) was
observed. Vessel volume tended to increase, whereas percentage atheroma volume
and lumen volume did not change. A significant negative correlation was observed
between percentage change in TAV and change in FFRCT (r = -0.185, p = 0.048). A
significant increase in calcified plaques (p = 0.01) and a decrease in
intermediate-attenuation plaques (p = 0.006) was observed. Conclusions: In
Japanese patients with diabetes and intermediate coronary artery stenosis,
alogliptin could not improve FFRCT or reduce atheroma volume, whereas the plaque
composition changed. A progression of atheroma volume was associated with a
reduction in FFRCT.
PMID- 29946565
TI - Prognostic value of proximal left coronary artery flow velocity detected by
transthoracic Doppler echocardiography.
AB - Background: Lesions in the proximal left coronary artery (LCA) are associated
with a poor prognosis compared with other lesional sites. Transthoracic Doppler
echocardiography (TTDE) can help to detect proximal LCA flow, and an accelerated
coronary flow velocity (CFV) indicates the presence of proximal LCA lesions. This
study aimed to investigate the prognostic value of CFV in the proximal LCA
measured by TTDE. Methods: We enrolled 1472 consecutive hemodynamically stable
patients with known or suspected heart disease whose CFV was successfully
detected using TTDE accompanied by routine echocardiography between 2008 and
2011. The primary outcome was cardiac death (acute myocardial infarction, heart
failure, or sudden cardiac death) and patients were followed up over a median of
6.3 years. Results: Overall, 42 cardiac deaths (3%) were observed. An increased
CFV was significantly associated with the outcome in several models based on
potential confounders (age, rate pressure product, Framingham Risk Score,
diabetes, coronary artery disease, hemoglobin, brain natriuretic peptide,
estimated glomerular filtration rate, left ventricular mass, left ventricular
ejection fraction, and E/e'). Using a receiver operating characteristic curve
analysis, the optimal cut-off value for the CFV to the association of the outcome
was 37 cm/s (area under the curve, 0.70; sensitivity, 82%; specificity, 62%). In
sequential Cox proportional hazards models, the CFV added incremental prognostic
information to the clinical and basic echocardiographic parameters (chi-squared:
110.7 to 146.6, P < 0.01). Conclusions: An increased CFV in the proximal LCA was
associated with cardiac death, incremental to the clinical and basic
echocardiographic parameters.
PMID- 29946566
TI - Association of frequent premature ventricular complex >10% and stroke-like
symptoms without a prior diagnosis of stroke or transient ischemic attack.
AB - Introduction: Premature ventricular complex (PVCs) detected from long-term ECG
recordings have been associated with an increased risk of ischemic stroke.
However, there was limited data about the association between high PVCs burdens
(>10%) and stroke-like symptoms without a prior diagnosis of stroke or transient
ischemic attack in the long-term follow up. Methods: The Kosin University 24
hours holter monitoring, echocardiography, electrocardiogram (ECG) database were
reviewed from 2013 to 2015 to identify patients with frequent PVCs (>10%). We
compared the long-term clinical outcomes between the patients with frequent PVCs
(>10%) and control group without PVC. Results: Among 572 patients who underwent
24-hours holter monitoring, finally, 373 consecutive patients (mean age; 59.5 +/-
15.8 years, 45.2% male) were enrolled. Among them, 203(54.4%) patients had high
PVCs burdens (>10%). There was no difference of the baseline characteristics. In
the long term follow-up, PVCs burden was not associated with PVCs -related
symptoms (P = 0.210). In univariate analysis, female, non-sustained ventricular
tachycardia (VT), sinus QRS duration, PVC coupling interval (CI), post- PVC CI,
and late precordial R-wave transition of PVCs were associated with PVCs-related
symptoms. In multivariate analysis, non-sustained VT (P = 0.022) and late
precordial R-wave transition of PVCs (P = 0.044) were independent risk factors
for PVCs-related stroke-like symptoms with frequent idiopathic PVCs > 10%.
Conclusion: High PVCs burdens (>10%) were associated with and stroke-like
symptoms without a prior diagnosis of stroke or transient ischemic attack in the
long-term follow up, suggesting more intensive medical therapy with close
clinical follow-up will be required.
PMID- 29946567
TI - Cardiovascular disease and brain health: Focus on white matter hyperintensities.
AB - Diseases affecting the brain contribute to a substantial proportion of morbidity
and mortality in the general population. Conditions such as stroke, dementia and
cognitive impairment have a prominent impact on global public health. Despite the
heterogeneous clinical manifestations of these conditions and their diverse
prognostic implications, current evidence supports a role for cardiovascular
disease as a common pathophysiological ground. Brain white matter
hyperintensities (WMH) are patchy white matter signal hyperintensity on T2
weighted magnetic resonance imaging sequences commonly found in elderly
individuals. WMH appear to have a vascular pathogenesis and have been shown to
confer an increased risk of stroke and cognitive decline. Indeed, they were
proposed as a marker for central nervous system frailty. Cardiovascular diseases
seem to play a key role in the etiology of WMH. Carotid atherosclerosis and
atrial fibrillation were shown to be associated with higher WMH burden, while
adequate blood pressure control has been reported reducing WMH progression. Aim
of the present work is to review the available evidence linking WMH to
cardiovascular disease, highlighting the complex interplay between cerebral and
cardiovascular health.
PMID- 29946568
TI - Modeling the Pseudomonas Sulfur Regulome by Quantifying the Storage and
Communication of Information.
AB - Bacteria are not simply passive consumers of nutrients or merely steady-state
systems. Rather, bacteria are active participants in their environments,
collecting information from their surroundings and processing and using that
information to adapt their behavior and optimize survival. The bacterial regulome
is the set of physical interactions that link environmental information to the
expression of genes by way of networks of sensors, transporters, signal cascades,
and transcription factors. As bacteria cannot have one dedicated sensor and
regulatory response system for every possible condition that they may encounter,
the sensor systems must respond to a variety of overlapping stimuli and collate
multiple forms of information to make "decisions" about the most appropriate
response to a specific set of environmental conditions. Here, we analyze
Pseudomonas fluorescens transcriptional responses to multiple sulfur nutrient
sources to generate a predictive, computational model of the sulfur regulome. To
model the regulome, we utilize a transmitter-channel-receiver scheme of
information transfer and utilize principles from information theory to portray P.
fluorescens as an informatics system. This approach enables us to exploit the
well-established metrics associated with information theory to model the sulfur
regulome. Our computational modeling analysis results in the accurate prediction
of gene expression patterns in response to the specific sulfur nutrient
environments and provides insights into the molecular mechanisms of Pseudomonas
sensory capabilities and gene regulatory networks. In addition, modeling the
bacterial regulome using the tools of information theory is a powerful and
generalizable approach that will have multiple future applications to other
bacterial regulomes. IMPORTANCE Bacteria sense and respond to their environments
using a sophisticated array of sensors and regulatory networks to optimize their
fitness and survival in a constantly changing environment. Understanding how
these regulatory and sensory networks work will provide the capacity to predict
bacterial behaviors and, potentially, to manipulate their interactions with an
environment or host. Leveraging the information theory provides useful
quantitative metrics for modeling the information processing capacity of
bacterial regulatory networks. As our model accurately predicted gene expression
profiles in a bacterial model system, we posit that the information theory-based
approaches will be important to enhance our understanding of a wide variety of
bacterial regulomes and our ability to engineer bacterial sensory and regulatory
networks.
PMID- 29946569
TI - Amodiaquine resistance in Plasmodium berghei is associated with PbCRT His95Pro
mutation, loss of chloroquine, artemisinin and primaquine sensitivity, and high
transcript levels of key transporters.
AB - Background: The human malaria parasite Plasmodium falciparum has evolved complex
drug evasion mechanisms to all available antimalarials. To date, the combination
of amodiaquine-artesunate is among the drug of choice for treatment of
uncomplicated malaria. In this combination, a short acting, artesunate is
partnered with long acting, amodiaquine for which resistance may emerge rapidly
especially in high transmission settings. Here, we used a rodent malaria parasite
Plasmodium berghei ANKA as a surrogate of P. falciparum to investigate the
mechanisms of amodiaquine resistance. Methods: We used serial technique to select
amodiaquine resistance by submitting the parasites to continuous amodiaquine
pressure. We then employed the 4-Day Suppressive Test to monitor emergence of
resistance and determine the cross-resistance profiles. Finally, we genotyped the
resistant parasite by PCR amplification, sequencing and relative quantitation of
mRNA transcript of targeted genes. Results: Submission of P. berghei ANKA to
amodiaquine pressure yielded resistant parasite within thirty-six passages. The
effective dosage that reduced 90% of parasitaemia (ED 90) of sensitive line and
resistant line were 4.29mg/kg and 19.13mg/kg, respectively. After freezing at
80oC for one month, the resistant parasite remained stable with an ED 90 of
18.22mg/kg. Amodiaquine resistant parasites are also resistant to chloroquine
(6fold), artemether (10fold), primaquine (5fold), piperaquine (2fold) and
lumefantrine (3fold). Sequence analysis of Plasmodium berghei chloroquine
resistant transporter revealed His95Pro mutation. No variation was identified in
Plasmodium berghei multidrug resistance gene-1 (Pbmdr1), Plasmodium berghei
deubiquitinating enzyme-1 or Plasmodium berghei Kelch13 domain nucleotide
sequences. Amodiaquine resistance is also accompanied by high mRNA transcripts of
key transporters; Pbmdr1, V-type/H+ pumping pyrophosphatase-2 and sodium hydrogen
ion exchanger-1 and Ca 2+/H + antiporter. Conclusions: Selection of amodiaquine
resistance yielded stable "multidrug-resistant'' parasites and thus may be used
to study common resistance mechanisms associated with other antimalarial drugs.
Genome wide studies may elucidate other functionally important genes controlling
AQ resistance in P. berghei.
PMID- 29946571
TI - How critical cost analysis can save money in today's NHS: a review of carpal
tunnel surgery in a district general hospital.
AB - With today's National Health Service (NHS) facing huge financial pressures the
healthcare profession cannot afford to carry on spending at the current rate.
Individual clinicians should be encouraged to critically appraise their own
practices to bring about a more efficient and cost-effective service. The purpose
of this project was to analyse the way that carpal tunnel surgery was being
performed within our institution and bring about safe changes to practice that
reduce expenditure. By critiquing our practices and applying simple changes based
around sound evidence an annual saving of over L15 500 to the department was
made. The changes instigated are simple, sustainable and safe to implement while
providing improved patient satisfaction. They are also easily transferrable
across institutions and to other minor hand surgical procedures to afford even
greater ongoing savings to the NHS.
PMID- 29946572
TI - Oxygen prescription: improving compliance using methods from BMJ Open Quality
journal.
AB - Oxygen is an important drug frequently used in the management of acutely unwell
hospital patients. However, oxygen overuse can have fatal side effects
particularly for those patients at risk of iatrogenic hypercapnia. British
Thoracic Society Guidelines state that oxygen must be prescribed for all
patients, with target saturations stipulated on the prescription for patient
safety. A quality improvement project was undertaken with the aim to improve the
oxygen prescription rate across the respiratory ward at a district general
hospital, over a period of 3 months. Quality improvement methods were implemented
based on data analysis at each stage, following discussion with senior doctors
and specialist nurses, and after reviewing previous quality improvement projects
published on BMJ Open Quality. The initial interventions of poster reminders and
multidisciplinary team education failed to significantly improve the rates of
oxygen prescription. Use of a targeted intervention where stickers were placed
above oxygen taps significantly improved prescription rate from 20% in the non
targeted group to 60% in the targeted group. This was based on a BMJ Open Quality
published improvement method. The current guidelines from the British Thoracic
Society, and hospital's own guidelines, advise good oxygen prescribing. However,
these recommendations alone are ineffective at achieving compliance among
prescribers. Further targeted interventions have shown improvements in oxygen
prescriptions and could lead to better clinical practice, patient care and
safety.
PMID- 29946570
TI - Detecting proliferation of adult hemocytes in Drosophila by BrdU incorporation.
AB - Drosophila and mammalian hematopoiesis share several similarities that ranges
from phases to the battery of transcription factors and signaling molecules that
execute this process. These resounding similarities along with the rich genetic
tools available in fruitfly makes it a popular invertebrate model to study blood
cell development both during normal and aberrant conditions. The larval system is
the most extensively studied to date. Several studies have shown that these
hemocytes just like mammalian counterpart proliferate and get routinely
regenerated upon infection. However, employing the same protocol it was concluded
that blood cell proliferation although abundant in larval stages is absent in
adult fruitfly. The current protocol describes the strategies that can be
employed to document the hemocyte proliferation in adulthood. The fact that a
subset of blood cells tucked away in the hematopoietic hub are not locked in
senescence, rather they still harbour the proliferative capacity to tide over
challenges was successfully demonstrated by this method. Although we have
adopted bacterial infection as a bait to evoke this proliferative capacity of the
hemocytes, we envision that it can also efficiently characterize the
proliferative responses of hemocytes in tumorigenic conditions as well as
scenarios of environmental and metabolic stresses during adulthood.
PMID- 29946573
TI - Bilateral recurrent macular holes.
AB - Purpose: To report an unusual case of bilateral recurrent full-thickness macular
holes (FTMH) in both eyes of a single patient over a 15-year period, with a total
of 3 FTMH in the right eye and 2 in the left eye. Each FTMH was successfully
treated with vitreous surgery, resulting in hole closure and visual acuity
improvement. Observations: During the previous 15 years, a 59-year-old female
developed a total of 3 FTMH in the right eye and 2 FTMH in the left eye. The
initial FTMH in each eye was surgically closed with pars plana vitrectomy (PPV),
epiretinal membrane (ERM) peeling, 14% C3F8 gas placement, and face down
positioning. Subsequent recurrences of FTMH, 2 in the right and 1 in the left,
were surgically closed with PPV and ERM peeling and/or indocyanine green-assisted
internal limiting membrane peeling, 14% C3F8 gas placement, and face down
positioning. Seven years following the last FTMH surgical closure, the patient's
best-corrected visual acuity was 20/50 in the right eye and 20/32 in the left eye
with no FTMH in either eye. Conclusions and importance: This case illustrates
that a rare individual may have more than one recurrent FTMH in both eyes. Final
visual outcome can be favorable following closure of more than one recurrent
FTMH.
PMID- 29946574
TI - Compilation of curvilinear-array EUS imaging demonstrating variant pancreatic
ductal anatomy with radiologic corroboration and motion animation.
PMID- 29946575
TI - Endoscopic submucosal dissection with a scissors-type knife for post-EMR
recurrence tumor involving the colon diverticulum.
PMID- 29946576
TI - Binge Drinking and Intergenerational Implications: Parental Preconception Alcohol
Impacts Offspring Development in Rats.
AB - Preconception behaviors and experiences of mothers and fathers can affect future
offspring. Recently, our laboratory showed that alcohol-naive offspring of
parents who were exposed to repeated binge alcohol during adolescence showed
altered DNA methylation patterns in the hypothalamus, a brain region involved in
regulation of pubertal development, stress, and behavior. These observations have
potentially far-reaching consequences for human health, as more than 4.6 million
Americans under the age of 21 years report engaging in the rapid intoxication
behavior of binge-pattern alcohol (EtOH) drinking. Therefore, we tested the
hypothesis that offspring of binge EtOH-exposed parents would have altered
hypothalamic function manifested phenotypically as improper pubertal development,
impaired socialization, and dysregulated stress response. In addition, we tested
the hypothesis that parental EtOH exposure would confer adaptive protection from
the negative effects of EtOH when offspring were themselves exposed to EtOH. Rats
received EtOH via oral gavage once daily for 6 days at both early [postnatal day
(PND) 37] and late puberty (PND 67). Animals were paired (EtOH-EtOH, vehicle
vehicle) for mating 24 hours after the last EtOH dose. After weaning, offspring
were randomized to vehicle treatment to assess changes in normal development or
to EtOH treatment to assess the effect of parental EtOH exposure on offspring
response to this treatment. We found that offspring had smaller body weights and
displayed fewer play behaviors when parents had been exposed to EtOH before
conception. In addition, offspring showed a reduction in pubertal development
markers that could indicate that parental preconception EtOH exposure confers
maladaptive epigenetic traits in first-generation offspring.
PMID- 29946577
TI - Association of Oral-Health Related Quality of Life and General Health Assessment
in Patients with Rheumatoid Arthritis.
AB - PURPOSE: To determine the impact of oral health related quality of life (OHRQoL)
on general health in patients suffering from rheumatoid arthritis (RA). MATERIALS
AND METHODS: Ninety-one patients with RA (mean age 52.82 +/- 11 years, 75.82%
female, 20.87% smokers) and 30 systemically healthy patients (control) were
evaluated for their OHRQoL by means of the Geriatric Oral Health Assessment Index
(GOHAI) and the Oral Health Impact Profile (OHIP)-14 questionnaires. Self
perceived RA status was assessed using the Routine Assessment of Patient Index
Data 3 (RAPID3). RESULTS: The mean SC-GOHAI score was 3.69 +/- 2.47 for RA
subjects and 1.36 +/- 2.69 in the control group. Statistically significant
differences were seen between RA and control groups (p < 0.05). RA patients with
and without periodontitis (PA) exhibited similar SC-GOHAI (Simple Count GOHAI)
scores (p = 0.980). No statistically significant differences were observed
between any of the groups, either for the OHIP 14-extent or for the OHIP 14
prevalence. RAPID3 scores showed that the majority of the RA patients (65.93%)
had high disease severity (RAPID3 >12, mean RAPID3 score 14.39 +/- 5.14).
Statistically significantly higher values were recorded for general health
assessment (PTGE, p = 0.009) and fatigue (FT, p = 0.004) in RA with PA as
compared to those without. SC-GOHAI with values between 5 and 8 was statistically
significantly associated with high severity health impairment (RAPID3 >12, p =
0.014, OR: 8.64). CONCLUSION: Within their limits, the present findings indicate
that: a) moderate OHRQoL as assessed by GOHAI may contribute to high severity
impairment of health in RA patients, and b) the GOHAI questionnaire may represent
a more adequate tool than OHIP-14 for assessing OHRQoL in patients suffering from
RA.
PMID- 29946578
TI - Oral Health Status of Stroke Patients Related to Residual Symptoms: A Case
Control Epidemiological Study in Hungary.
AB - PURPOSE: Stroke is a leading cause of death in developed countries. Recently, its
connection with oral health has been a focus of the medical literature. The aim
of this study was therefore to statistically examine the oral health of subjects
who previously suffered from stroke and provide a guide for the dental treatment
of these patients. MATERIALS AND METHODS: Stroke patients at least one year after
the stroke episode and age- and sex-matched healthy controls were examined:
dental and medical stroke histories were recorded, followed by a detailed
orofacial examination. A categorisation into three 'dental' subgroups of stroke
patients was carried out based on their residual symptoms, the functional
deficiency of limbs, and chewing and swallowing difficulties. Indices quantifying
oral hygiene (OHI-S), dental status explained by the number of decayed, missing,
and filled teeth (DMFT), periodontal status (CAL, CPITN, Muhlemann index), and
the status of prosthetic treatment (prosthetic index) were assessed. Statistical
comparison was performed between the patient and age- and sex-matched control
subjects, as well as between subgroups of stroke patients. RESULTS: One hundred
two stroke patients and 98 healthy age- and sex-matched control subjects were
examined. The oral health and dental status of stroke patients was worse compared
with the control group. Stroke patients had significantly more decayed (2.3 +/- 3
vs1.1 +/- 1.8; p = 0.01) and missing (19.3 +/- 9.5 vs 15.5 +/- 9.3; p = 0.005)
teeth, but significantly fewer filled (3.6 +/- 4.7 vs 7.7 +/- 5.6; p < 0.001)
teeth than did the healthy controls. In stroke patients, clinical attachment loss
(CAL) was double that of the control group (p < 0.001). A comparison between the
subgroups of stroke patients revealed that the most severe findings were in
patients who had chewing and swallowing disabilities. DISCUSSION: According to
these results, the combination of risk factors of stroke, residual neurological
signs after stroke, and poorer socioeconomic conditions results in poor oral
hygiene, poor dental and periodontal conditions, and a lower prosthetic index.
Special care and attention should be given to the oral hygiene and dental
treatment of such patients, to enable good nourishment.
PMID- 29946579
TI - Cowden Syndrome Associated with Severe Periodontal Disease: A Short Literature
Review and a Case Report.
AB - PURPOSE: The aim of this literature review and case report was to point out the
relationship between Cowden Syndrome (CS) and severe periodontitis. CS is a rare
autosomal dominant disorder characterised by skin and oral hamartomas, and is
associated with an increased risk of cancer development. CASE REPORT: The case of
a 43-year old male patient affected by Cowden syndrome and presenting severe
periodontitis was reported. RESULTS: It can be suggested that the specific
gingival morphology of the patient with CS might be a risk factor for the
development of periodontal disease, as described in the present case report.
CONCLUSION: Early diagnosis is crucial in patients affected by CS. The dentist
may be the first to notice any atypical changes in the oral cavity and refer the
patient for further examinations. Moreover, the mucosal and skin changes have a
tendency to appear prior to the malignancies associated with the syndrome. This
highlights the responsibility of the dentist in the early diagnosis of this
progressive pathological syndrome.
PMID- 29946580
TI - Highly strained [6]cycloparaphenylene: crystallization of an unsolvated polymorph
and the first mono- and dianions.
AB - An X-ray diffraction study of [6]cycloparaphenylene (1), crystallized under
solvent-free conditions, revealed a unique solid state structure with tight
packing of individual molecules that minimizes empty internal space. The
controlled chemical reduction of this highly strained nanohoop with Group 1
metals resulted in the first isolation and structural characterization of its
mono- and dianions, allowing for the evaluation of core transformations for the
series ranging from 10 to 11- and 12-.
PMID- 29946581
TI - Solvothermal flow synthesis of zinc phosphate pigment.
AB - Synthesis of phase pure hopeite pigment through a solvothermal flow method is
reported here for the first time. The products show two-step dehydration
behaviour from thermogravimetric analysis (TGA), and a higher degree of purity
and homogeniety than commercial zinc phosphate pigment. By increasing the
reaction temperature stepwise from room temperature to 350 degrees C it was
possible to decrease the size of the individual crystallite sheets and to tune
their packing into larger assemblies. The conversion of reactants to product
proved to be significantly higher at increased temperature with a measured yield
of 98.7% at 250 degrees C versus 85.4% at room temperature. The synthesis route
demonstrated here is environmentally sustainable, increases cost-efficiency
through minimization of waste, and is compatible with a scale-up strategy.
PMID- 29946582
TI - Parameter control for enhanced peak-to-valley current ratio in a MoS2/MoTe2 van
der Waals heterostructure.
AB - The Ids-Vds properties of a van der Waals cross-junction of few layered
MoS2/MoTe2 were investigated, and the physical device parameters were altered in
order to transform the conduction mechanism from thermionic emission to interband
tunneling. The pristine heterostructure demonstrated rectification behavior of
typical p-n junction diodes, because of the p-type and n-type nature of MoTe2 and
MoS2, respectively. Lowering the contact resistance between the metal and channel
materials, by changing the electrode metals from Au to Pd and Ti, alone did not
give rise to carrier conduction through the hetero-interband tunneling between
MoTe2 and MoS2. In addition to the reduction in contact resistance, the chemical
doping of MoS2 using Benzyl Viologen (BV) achieves hetero-interband tunneling
between MoTe2 and MoS2, which probably narrows the depletion layer by
degenerating MoS2. The peak-to-valley ratio of the tunneling current of the BV
doped heterostructure of MoS2/MoTe2 is about 4.8, which is comparable to that of
the commercially available Si tunneling diode.
PMID- 29946583
TI - A new twist on sea silk: the peculiar protein ultrastructure of fan shell and
pearl oyster byssus.
AB - Numerous mussel species produce byssal threads - tough proteinaceous fibers,
which anchor mussels in aquatic habitats. Byssal threads from Mytilus species,
which are comprised of modified collagen proteins - have become a veritable
archetype for bio-inspired polymers due to their self-healing properties.
However, threads from different species are comparatively much less understood.
In particular, the byssus of Pinna nobilis comprises thousands of fine fibers
utilized by humans for millennia to fashion lightweight golden fabrics known as
sea silk. P. nobilis is very different from Mytilus from an ecological,
morphological and evolutionary point of view and it stands to reason that the
structure-function relationships of its byssus are distinct. Here, we performed
compositional analysis, X-ray diffraction (XRD) and transmission electron
microscopy (TEM) to investigate byssal threads of P. nobilis, as well as a
closely related bivalve species (Atrina pectinata) and a distantly related one
(Pinctada fucata). This comparative investigation revealed that all three threads
share a similar molecular superstructure comprised of globular proteins organized
helically into nanofibrils, which is completely distinct from the Mytilus thread
ultrastructure, and more akin to the supramolecular organization of bacterial
pili and F-actin. This unexpected discovery hints at a possible divergence in
byssus evolution in Pinnidae mussels, perhaps related to selective pressures in
their respective ecological niches.
PMID- 29946584
TI - The anti-adhesive effect of glycoclusters on Pseudomonas aeruginosa bacteria
adhesion to epithelial cells studied by AFM single cell force spectroscopy.
AB - The human opportunistic pathogen Pseudomonas aeruginosa (PA) is responsible for
chronic infections of the respiratory epithelium in cystic fibrosis patients. PA
takes advantage of an arsenal of virulence factors to infect and colonize human
lungs. Among them, the lectin LecA favours epithelium invasion by interacting
with host cell globotriaosylceramide (Gb3). A new therapeutic approach is based
on the development of synthetic multivalent molecules (glycoclusters) targeting
LecA with a higher affinity than its natural ligand. Atomic force microscopy
single cell force spectroscopy has been used to study the effect of glycoclusters
on the bacteria-cell interaction. Glycoclusters have been shown to affect the
detachment work and detachment force of the bacteria-cell interaction. The
specificity and the efficiency of the glycocluster in targeting the lectin and
destabilizing the PA-epithelial cell adhesion are demonstrated and discussed.
PMID- 29946585
TI - Magnetic relaxation in cobalt(ii)-based single-ion magnets influenced by
distortion of the pseudotetrahedral [N2O2] coordination environment.
AB - The synthesis, structure, and magnetic properties of two mononuclear cobalt(ii)
complexes [Co(LSal,2-Ph)2] (1) and [Co(LNph,2-Ph)2] (2) are reported. The
utilized sterically demanding Schiff-base ligands HLSal,2-Ph (2-(([1,1'-biphenyl]
2-ylimino)methyl)phenol) and HLNph,2-Ph (1-(([1,1'-biphenyl]-2
ylimino)methyl)naphthalen-2-ol) lead to a strong distortion of the [N2O2]
coordination environment in the complexes 1 and 2, which can be primarily
attributed to the variation in the dihedral angle between the planes of the two
chelate ligands. Magnetic susceptibility and FD-FT THz-EPR measurements as well
as ab initio calculations reveal that both complexes exhibit an easy-axis type of
anisotropy. For both compounds frequency-dependent ac susceptibility measurements
show an out-of-phase susceptibility under applied static fields of 400 and 1000
Oe. A detailed analysis of the underlying relaxation process is given, revealing
significant differences in the contributions of Orbach, Raman, and direct
processes within the observed temperature range. Fitting of the magnetic data
leads to a spin-reversal barrier of 49 cm-1 for 1 at an applied field of 1000 Oe.
For 2 the barrier is not well defined by the analysis of the relaxation times and
is, therefore, approximated by the experimental barrier derived from FD-FT THz
EPR measurements (62.8 cm-1). The results from ab initio calculations and FD-FT
THz-EPR measurements show that the distortion of the coordination sphere in
complexes 1 and 2 from the pseudotetrahedral towards a square-planar coordination
geometry leads to an increase in both the axial (D) and the rhombic zero-field
splitting (E).
PMID- 29946586
TI - Silver nanoparticle embedded copper oxide as an efficient core-shell for the
catalytic reduction of 4-nitrophenol and antibacterial activity improvement.
AB - A facile and eco-friendly method was developed to prepare a microporous CuO@Ag0
core-shell with high catalytic and antibacterial activities. Scanning and
transmission electron microscopy revealed a preponderance of nearly spherical 50
nm particles with slight structure compaction. Comparison of the hysteresis loops
confirmed the structure compaction after AgNP incorporation, and a significant
decrease of the specific surface area from 55.31 m2 g-1 for CuO to 8.03 m2 g-1
for CuO@Ag0 was noticed. A kinetic study of 4-nitrophenol (4-NP) reduction into 4
aminophenol (4-AP) with sodium borohydride revealed a first order reaction that
produces total conversion in less than 18 minutes. CuO@Ag0 also exhibited
appreciable antibacterial activity against Staphylococcus aureus. The
antibacterial effects were found to strongly depend on the size, contact surface,
morphology and chemical composition of the catalyst particles. The addition of
Ag0-NPs produced more reactive oxygen species in the bacteria medium. These
results open promising prospects for its potential applications as a low cost
catalyst in wastewater treatment and antibacterial agent in cosmetics.
PMID- 29946587
TI - One-step hydrothermal synthesis of chiral carbon dots and their effects on mung
bean plant growth.
AB - Chiral compounds/materials have important effects on the growth of plants. Chiral
carbon dots (CDs), as an emerging chiral carbon nanomaterial, have great
potential in bio-application and bio-nanotechnology. Herein, we report a
hydrothermal method to synthesize chiral CDs from cysteine (cys) and citric acid.
These chiral CDs were further demonstrated to have systemic effects on the growth
of mung bean plants, in which case both l- and d-CDs can promote the growth of
the root in mung bean plants, stem length of mung bean sprouts and water
absorption of bean seeds. The elongation of mung bean sprouts presented an
increasing trend with the treatment of chiral CDs of increasing concentration
(below 500 MUg mL-1). Furthermore, in the optimal concentration (100 MUg mL-1),
the l-CDs can improve root vigor and the activity of the Rubisco enzyme of bean
sprouts by 8.4% and 20.5%, while the d-CDs increased by 28.9% and 67.5%. Due to
more superior properties in improving root vigor and the activity of the Rubisco
enzyme of mung bean sprouts, d-CDs are able to enhance photosynthesis better and
accumulate more carbohydrate in mung bean plants.
PMID- 29946588
TI - CxNy particles@N-doped porous graphene: a novel cathode catalyst with a
remarkable cyclability for Li-O2 batteries.
AB - Despite the intrinsic advantages of ultra-high theoretical capacity and energy
density of lithium-O2 batteries, there remain several critical issues to be
resolved, especially the two concerning poor cyclability and rate capability. In
this work, CxNy particles@N-doped porous graphene (CxNy@NPG) with a novel three
dimensional architecture is successfully synthesized via a simple template method
and employed as the cathode catalyst of Li-O2 batteries. It is surprisingly found
that the as-synthesized CxNy@NPG cathode not only demonstrates a remarkable
cycling performance of 200 cycles at 1000 mA g-1 but also an intriguing high-rate
capability with 8892 mA h g-1 at 1000 mA g-1, both of which can be attributed to
a synergistic effect between the unique 3D porous structure and an effective N
doping. Specifically, it is believed that the unique porous 3D structure will, on
one hand, build numerous microchannels, thus facilitating rapid O2 diffusion, and
on the other hand, provide sufficient storage space to accommodate adequate
discharge products. Indispensably, it is also believed that the N-doped porous
graphene enables improved bifunctional catalytic activities towards both oxygen
reduction reaction (ORR) and oxygen evolution reaction (OER), thus decreasing the
discharge/charge overpotential, and reducing undesired side reactions. It is
anticipated that the new 3D porous CxNy@NPG provides an inspiring route to design
long cycling and high-rate performance cathodes for Li-O2 batteries.
PMID- 29946589
TI - Rhodium-catalyzed oxidative C-H/C-H cross-coupling of aniline with heteroarene: N
nitroso group enabled mild conditions.
AB - The development of transition metal-catalyzed oxidative C-H/C-H cross-coupling
between two (hetero)arenes to forge aryl-heteroaryl motifs under mild conditions
is an appealing yet challenging task. Herein, we disclose a rhodium-catalyzed
oxidative C-H/C-H cross-coupling reaction of an N-nitrosoaniline with a
heteroarene under mild conditions. The judicious choice of the N-nitroso group as
a directing group enables heightened reactivity. The coupled products could be
transformed expediently to (2-aminophenyl)heteroaryl skeletons.
PMID- 29946590
TI - Visible light driven catalytic gold decorated soft-oxometalate (SOM) based
nanomotors for organic pollutant remediation.
AB - Visible light propelled nanomotors are a class of highly sought after active
matter. Here we report a gold decorated semiconductor and a soft-oxometalate
based TiO2-{Mo7}-Au nanomotor which can be propelled diffusiophoretically on
exposure to visible light and show excellent photocatalytic activity. These
systems exclude the use of any harsh toxic chemical as fuel and exhibit a speed
of 10 MUm s-1 in water. Their motion can also be controlled by rapid switching of
light. We use these photocatalytic nanomotors for environmental cleansing as they
can facilitate the removal of organic pollutants from water under visible light.
In this work we have demonstrated the removal of two model organic pollutants
methylene blue and benzyl bromide from water using these nanomotors.
PMID- 29946596
TI - Single-cell membrane drug delivery using porous pen nanodeposition.
AB - Delivering molecules onto the plasma membrane of single cells is still a
challenging task in profiling cell signaling pathways with single cell
resolution. We demonstrated that a large quantity of molecules could be targeted
and released onto the membrane of individual cells to trigger signaling
responses. This is achieved by a porous pen nanodeposition (PPN) method, in which
a multilayer porous structure, serving as a reservoir for a large amount of
molecules, is formed on an atomic force microscope (AFM) tip using layer-by-layer
assembly and post processing. To demonstrate its capability for single cell
membrane drug delivery, PPN was employed to induce a calcium flux triggered by
the binding of released antibodies to membrane antigens in an autoimmune skin
disease model. This calcium signal propagates from the target cell to its
neighbors in a matter of seconds, proving the theory of intercellular
communication through cell-cell junctions. Collectively, these results
demonstrated the effectiveness of PPN in membrane drug delivery for single cells;
to the best of our knowledge, this is the first technique that can perform the
targeted transport and delivery in single cell resolution, paving the way for
probing complex signaling interactions in multicellular settings.
PMID- 29946597
TI - Preparation and reactivity of half-sandwich dioxygen complexes of ruthenium.
AB - Dioxygen complexes [Ru(eta5-C5Me5)(eta2-O2){P(OEt)3}2]BPh4 (1) and [Ru(eta5
C5Me5)(eta2-O2)(PPh3){P(OR)3}]BPh4 (2, 3) [R = Me (2), Et (3)] were prepared by
allowing chloro-complexes RuCl(eta5-C5Me5)[P(OEt)3]2 and RuCl(eta5
C5Me5)(PPh3)[P(OR)3] to react with air (1 atm) in the presence of NaBPh4.
Substitution of the eta2-O2 in 1-3 by alkenes [CH2[double bond, length as m
dash]CH2, [upper bond 1 start]CH[double bond, length as m-dash]CHCO(O)C[upper
bond 1 end]O] and terminal alkynes (PhC[triple bond, length as m-dash]CH)
afforded [Ru(eta5-C5Me5)(eta2-CH2[double bond, length as m
dash]CH2){P(OEt)3}L]BPh4 (4) [L = P(OEt)3 (a), PPh3 (b)], [Ru(eta5-C5Me5){eta2
[upper bond 1 start]CH[double bond, length as m-dash]CHCO(O)C[upper bond 1
end]O}{P(OEt)3}2]BPh4 (5) and [Ru(eta5-C5Me5){[double bond, length as m
dash]C[double bond, length as m-dash]C(H)Ph}{P(OEt)3}2]BPh4 (6) derivatives.
Protonation of dioxygen complexes 1-3 with triflic acid yielded phosphate
complexes [Ru(kappa1-OTf)(eta5-C5Me5){P(O)(OEt)3}2] (7) and [Ru(kappa1-OTf)(eta5
C5Me5){P(O)Ph3}{P(O)(OMe)3}] (8). A reaction path for the formation of complexes
7 and 8 is proposed by DFT studies. Besides phosphate complex 7, protonation of 1
under a CH2[double bond, length as m-dash]CH2 atmosphere (1 atm) afforded acetic
acid. Treatment of complexes 7 and 8 with tBuNC afforded the tris(isocyanide)
derivative [Ru(eta5-C5Me5)(tBuNC)3]BPh4 (9). The complexes were characterised
spectroscopically (IR and NMR) and by X-ray crystal structure determination of 1,
2 and 3.
PMID- 29946598
TI - 3D cell electrorotation and imaging for measuring multiple cellular biophysical
properties.
AB - 3D rotation is one of many fundamental manipulations to cells and imperative in a
wide range of applications in single cell analysis involving biology, chemistry,
physics and medicine. In this article, we report a dielectrophoresis-based, on
chip manipulation method that can load and rotate a single cell for 3D cell
imaging and multiple biophysical property measurements. To achieve this, we
trapped a single cell in constriction and subsequently released it to a rotation
chamber formed by four sidewall electrodes and one transparent bottom electrode.
In the rotation chamber, rotating electric fields were generated by applying
appropriate AC signals to the electrodes for driving the single cell to rotate in
3D under control. The rotation spectrum for in-plane rotation was used to extract
the cellular dielectric properties based on a spherical single-shell model, and
the stacked images of out-of-plane cell rotation were used to reconstruct the 3D
cell morphology to determine its geometric parameters. We have tested the
capabilities of our method by rotating four representative mammalian cells
including HeLa, C3H10, B lymphocyte, and HepaRG. Using our device, we quantified
the area-specific membrane capacitance and cytoplasm conductivity for the four
cells, and revealed the subtle difference of geometric parameters (i.e., surface
area, volume, and roughness) by 3D cell imaging of cancer cells and normal
leukocytes. Combining microfluidics, dielectrophoresis, and microscopic imaging
techniques, our electrorotation-on-chip (EOC) technique is a versatile method for
manipulating single cells under investigation and measuring their multiple
biophysical properties.
PMID- 29946599
TI - Polymer-grafted nanoparticles prepared via a grafting-from strategy: a computer
simulation study.
AB - Nanoparticles (NPs) grafted with polymer chains prepared via a grafting-from
strategy are studied through coarse-grained molecular dynamics simulations
combined with our stochastic reaction model. A system involving multiple
individual NPs, with grafting-from processes for all the NPs induced
simultaneously, is simulated, so that chain growth competition on the same NP, as
well as between neighbouring NPs, are both naturally considered. Our results
imply that there should be an optimized range of NP sizes, as compared to monomer
size, in which initiator sites are most easily induced. Besides, when the
initiator density is high, a shielding effect from the sparse long chains on the
most short chains or initiators evidently yields an extremely unbiased
distribution of chains. We also adopt a representative polymer-tethered NP
prepared via a grafting-from strategy to study the potential of mean force
between NPs, so that the dispersion and stabilization abilities of such polymer
grafted NPs in a polymer matrix can be generally predicted during the preparation
of polymer nanocomposite materials. Our study helps to elucidate the cause of
chain dispersity during the grafting-from process and could act as a guide for
better design and to improve the performance of polymer nanocomposites.
PMID- 29946600
TI - A macrocyclic receptor containing two viologen species connected by conjugated
terphenyl groups.
AB - A macrocyclic receptor molecule containing two viologen species connected by
conjugated terphenyl groups has been designed and synthesised. The single-crystal
X-ray structure shows that the two viologen residues have a transannular NN
separation of ca. 7.4 A. Thus, the internal cavity dimensions are suitable for
the inclusion of pi-electron-rich species. The macrocycle is redox active, and
can accept electrons from suitable donor species including triethylamine,
resulting in a dramatic colour change from pale yellow to dark green as a
consequence of the formation of a paramagnetic bis(radical cationic) species.
Cyclic voltammetry shows that the macrocycle can undergo two sequential and
reversible reduction processes (E1/2 = -0.65 and -0.97 V vs. Fc/Fc+). DFT and TD
DFT studies accurately replicate the structure of the tetracationic macrocycle
and the electronic absorption spectra of the three major redox states of the
system. These calculations also showed that during electrochemical reduction, the
unpaired electron density of the radical cations remained relatively localised
within the heterocyclic rings. The ability of the macrocycle to form
supramolecular complexes was confirmed by the formation of a pseudorotaxane with
a guest molecule containing a pi-electron-rich 1,5-dihydroxynaphthalene
derivative. Threading and dethreading of the pseudorotaxane was fast on the NMR
timescale, and the complex exhibited an association constant of 150 M-1 (+/-30 M
1) as calculated from 1H NMR titration studies.
PMID- 29946601
TI - Copper-related toxicity in replicating and dormant Mycobacterium tuberculosis
caused by 1-hydroxy-5-R-pyridine-2(1H)-thiones.
AB - With the emerging primary resistance of Mycobacterium tuberculosis to current
drugs and wide distribution of latent tuberculosis infection, the need for new
compounds with a novel mode of action is growing. Copper-mediated innate immunity
and its antibacterial toxicity pose novel strategies for tuberculosis drug
discovery and development. Transcriptome response to 1-hydroxy-5-R-pyridine-2(1H)
thiones, which were found to be highly active in vitro against actively growing
and dormant nonculturable M. tuberculosis, revealed signs of copper toxicity. 1
Hydroxy-5-R-pyridine-2(1H)-thiones were found to form stable charged lipophilic
complexes with Cu2+ ions that could transport into mycobacterial cells. Copper
accumulated inside treated bacilli as subsequent metabolic destruction of the
complex led to chemical transformation of 1-hydroxy-5-R-pyridine-2(1H)-thiones
and release of free Cu2+ into the cytoplasm. 1-Hydroxy-5-R-pyridine-2(1H)-thiones
are a potent class of Cu-dependent inhibitors of M. tuberculosis, and may control
infection by impairment of copper homeostasis.
PMID- 29946602
TI - Correction: Achieving biopolymer synergy in systems chemistry.
AB - Correction for 'Achieving biopolymer synergy in systems chemistry' by Yushi Bai
et al., Chem. Soc. Rev., 2018, DOI: 10.1039/c8cs00174j.
PMID- 29946603
TI - Synthetic access to isoxazoline-functionalized isoquinolines via microwave
assisted iminoxyl radical-participated cascade cyclization of vinyl isocyanides.
AB - A convenient microwave-assisted method for the synthesis of isoxazoline
functionalized isoquinolines via the n-Bu4NI (TBAI) catalyzed radical cascade
cyclization of vinyl isocyanides with beta,gamma-unsaturated ketoximes has been
described. The methodology presented here achieves a wide substrate scope and
good to excellent yields. A radical mechanism is proposed, which is supported by
the intermolecular competing kinetic isotope effect (KIE) experiment and the
radical trapping experiment.
PMID- 29946604
TI - Bipyrrolidine salan alkoxide complexes of lanthanides: synthesis,
characterisation, activity in the polymerisation of lactide and mechanistic
investigation by DOSY NMR.
AB - Four dimeric lanthanide alkoxide complexes bearing ONNO bipyrrolidine salan
ligands (LMeH2/LtBuH2) have been prepared with Nd, Sm and Yb. Depending on the
metal and substituents, these complexes adopt varying coordination geometries.
While investigating the hydrolytic degradation of these complexes, three dimeric
mixed alkoxide/hydroxide and bis-hydroxide products were also prepared, isolated
and characterised. Despite paramagnetism, 1H NMR and diffusion ordered
spectroscopy (DOSY) allowed additional characterisation alongside elemental and
single-crystal X-ray diffraction analyses. These systems were very active for the
controlled ring-opening polymerisation (ROP) of rac-lactide (LA), under
industrially relevant melt conditions and in solution, yielding complete
conversion within 5 minutes at [Ln] : [LA] ratios of up to 3000 : 1 in toluene,
and at 80 degrees C, whilst retaining low dispersities (D = 1.1). 1H DOSY NMR
spectroscopy was employed to monitor polymer growth from the metal centres in
situ, and revealed a dinuclear catalytically active species.
PMID- 29946605
TI - Covalently bonded multimers of Au25(SBut)18 as a conjugated system.
AB - Aromatic dithiol linkers were used to prepare aggregates of Au25(SR)18 clusters
(SR: thiolate) via ligand exchange reactions. Fractions of different aggregate
sizes were separated by size exclusion chromatography (SEC). The aggregates were
characterized by UV-vis absorption spectroscopy, matrix assisted laser desorption
ionization (MALDI) mass spectrometry, nuclear magnetic resonance (NMR)
spectroscopy (including diffusion-ordered spectroscopy, DOSY) and small angle X
ray scattering (SAXS). At a 2 : 1 cluster : dithiol ratio, small aggregates
(dimers, trimers) and also larger aggregates consisting of 10-20 Au25 clusters
were formed, according to DOSY, besides unreacted (monomeric) Au25(SR)18. MALDI
mass spectrometry shows signals consistent with dimers and trimers (doubly
charged). The SAXS curves for the small aggregates can be well fitted by a pearl
necklace model. For the bigger aggregates the SAXS curves evidence a
characteristic separation distance between the clusters within the aggregates,
which is imposed by the length of the linker. The SAXS curves of these larger
aggregates can be well fitted with a core-shell sphere model with a sticky hard
sphere structure factor, in agreement with closely packed aggregates. The
absorption spectra of smaller aggregates resemble those of individual Au25(SR)18
clusters; however, and most importantly, the larger aggregates show completely
different, less structured spectra with a new band emerging at 840 nm. We assign
this drastic change in the absorption spectra and the new band to the electronic
coupling between the clusters through the all aromatic linker. In accordance with
this view, the aggregates formed with a linker containing methylene groups, thus
breaking conjugation, do not show the band at 840 nm. By the addition of
monothiols to the larger aggregates their size can be reduced through an
"unlinking" reaction. This reaction also affects the band at 840 nm, which moves
to higher energy when reducing the aggregate size, as would be expected within a
particle in a box model. The electronic coupling between the clusters through the
linker is the basis for future applications in nanoelectronics.
PMID- 29946606
TI - Nanoengineering ABO3 active sites from low-energy routes (TX100-stabilised water
in-oil microemulsions, surface segregation and surface complexation on colloidal
AlOOH/sol-gel Al2O3 surfaces) for pollution control catalysis.
AB - It is shown that water-in-oil microemulsions (m/e or MUE) can produce BaCeO3
(BCO) and LaCoO3 (LCO) precursors. The nanoparticles (NPs) adsorb on AlOOH sols,
in much the same way as Turkevich previously immobilised platinum group metal
sols. BCO is active in CO and propane oxidation and NO removal under
stoichiometric exhaust conditions, but LCO is a better oxidation catalyst.
Activity was also seen when Ba,Ce and La,Co are inserted into/segregate at the
surface of AlOOH/Al2O3. However, there is only formation of low levels of BCO,
CAIO3 (CAO), LCO and LaAIO3 (LAO) perovskites, along with aluminates and separate
oxides. The complexing of cations by AlOOH surface-held oxalate ions, albeit with
different efficiencies, has also been explored. All three routes yield active
catalysts with micro-domains of crystallinity; microemulsions produce the best
defined perovskite NPs, but even those from surface segregation have higher
turnover numbers than traditional Pt catalysts. Perovskite NPs may open up green
chemistry for air pollution control that is consistent with a circular economy.
PMID- 29946607
TI - Enabling multi-electron reaction of epsilon-VOPO4 to reach theoretical capacity
for lithium-ion batteries.
AB - By controlling the morphology and particle size of the epsilon polymorph of
vanadyl phosphate, epsilon-VOPO4, it can fully reversibly intercalate two Li-ions
and reach the theoretical capacity of 305 mA h g-1 over two voltage plateaus at
about 4.0 and 2.5 V.
PMID- 29946608
TI - Plasmon-enhanced versatile optical nonlinearities in a Au-Ag-Au multi-segmental
hybrid structure.
AB - A Au-Ag-Au multi-segmental hybrid structure has been synthesized by using an
electrodeposition method based on an anodic aluminum oxide (AAO) membrane. The
third-order optical nonlinearities, second harmonic generation (SHG) and
photoluminescence (PL) properties containing ultrafast supercontinuum generation
and plasmon mediated thermal emission have been investigated. Significant optical
enhancements have been obtained near surface plasmon resonance wavelength in all
the abovementioned nonlinear processes. Comparative studies between the Au-Ag-Au
multi-segmental hybrid structure and the corresponding single-component Au and Ag
hybrid structures demonstrate that the Au-Ag-Au multi-segmental hybrid structure
has much larger optical nonlinearities than its counterparts. These results
demonstrate that the Au-Ag-Au hybrid structure is a promising candidate for
applications in plasmonic devices and enhancement substrates.
PMID- 29946610
TI - The effects of implicit modeling of nonpolar solvation on protein folding
simulations.
AB - Implicit solvent models, in which the polar and nonpolar solvation free-energies
of solute molecules are treated separately, have been widely adopted for
molecular dynamics simulation of protein folding. While the development of the
implicit models is mainly focused on the methodological improvement and key
parameter optimization for polar solvation, nonpolar solvation has been either
ignored or described by a simplistic surface area (SA) model. In this work, we
performed the folding simulations of multiple beta-hairpin and alpha-helical
proteins with varied surface tension coefficients embedded in the SA model to
clearly demonstrate the effects of nonpolar solvation treated by a popular SA
model on protein folding. The results indicate that the change in the surface
tension coefficient does not alter the ability of implicit solvent simulations to
reproduce a protein native structure but indeed controls the components of the
equilibrium conformational ensemble and modifies the energetic characterization
of the folding transition pathway. The suitably set surface tension coefficient
can yield explicit solvent simulations and/or experimentally suggested folding
mechanism of protein. In addition, the implicit treatment of both polar and
nonpolar components of solvation free-energy contributes to the overestimation of
the secondary structure in implicit solvent simulations.
PMID- 29946611
TI - Cooperative bimetallic reactivity of a heterodinuclear molybdenum-copper model of
Mo-Cu CODH.
AB - The synthesis of a heterodinucleating ligand LH2 (LH2 = (E)-3-(((2,7-di-tert
butyl-9,9-dimethyl-5-((pyridin-2-ylmethylene)amino)-9H-xanthen-4
yl)amino)methyl)benzene-1,2-diol) was undertaken toward a functional model of the
bimetallic active site found in Mo-Cu carbon monoxide dehydrogenase (Mo-Cu CODH),
and to understand the origins of heterobimetallic cooperativity exhibited by the
enzyme. LH2 features a hard potentially dianionic catechol chelate for binding
Mo(vi) and a soft iminopyridine chelate for binding Cu(i). Treatment of LH2 with
either Cu(i) or M(vi) (M = Mo, W) sources leads to the anticipated site-selective
incorporation of the respective metals. While both [CuI(LH2)]+ and [MVIO3(L)]2-
complexes are stable in the solid state, [MVIO3(L)]2- complexes disproportionate
in solution to give [MVIO2(L)2](NEt4)2 complexes, with [MVIO4]2- as the by
product. The incorporation of BOTH Mo(vi) and Cu(i) into L forms a highly
reactive heterobimetallic complex [MoVIO3CuI(L)](NEt4)2, whose formation and
reactivity was interrogated via1H NMR/UV-vis spectroscopy and DFT calculations.
These studies reveal that the combination of the two metals triggers oxidation
reactivity, in which a nucleophilic Mo(vi) trioxo attacks Cu(i)-bound imine. The
major product of the reaction is a crystallographically characterized
molybdenum(vi) complex [Mo(L')O2](NEt4) coordinated by a modified ligand L' that
contains a new C-O bond in place of the imine functionality. This observed
hydroxylation reactivity is consistent with the postulated first step of Mo-Cu
CODH (nucleophilic attack of the Mo(vi)-oxo on the Cu(i)-bound electrophilic CO)
and xanthine oxidoreductase (nucleophilic attack of Mo(vi)-oxo on the
electrophilic xanthine carbon).
PMID- 29946609
TI - The efficiency of 18F labelling of a prostate specific membrane antigen ligand
via strain-promoted azide-alkyne reaction: reaction speed versus hydrophilicity.
AB - Here we report the 18F labeling of a prostate specific membrane antigen (PSMA)
ligand via a strain promoted oxa-dibenzocyclooctyne (ODIBO)- or
bicyclo[6.1.0]nonyne (BCN)-azide reaction. Although ODIBO reacts with azide 20
fold faster than BCN, in vivo PET imaging suggests that 18F-BCN-azide-PSMA
demonstrated much higher tumor uptake and a much higher tumor to background
contrast.
PMID- 29946612
TI - Magnetic relaxation and three-dimensional critical fluctuations in B-doped Q
carbon - a high-temperature superconductor.
AB - Dimensional fluctuations and magnetic relaxations in high-temperature
superconductors are key considerations for practical applications in high-speed
electronic devices. We report the creep of trapped magnetic flux and three
dimensional critical fluctuations near the superconducting transition temperature
(Tc = 36 K) in B-doped amorphous Q-carbon. The superconducting phase in B-doped Q
carbon is formed by nanosecond pulsed laser melting in a super undercooled state
followed by subsequent quenching. Time-dependent magnetic moment measurements in
the B-doped Q-carbon follow the Anderson-Kim logarithmic decay model with the
calculated value of pinning potential to be 0.75 eV at 1 T near Tc. There is also
strong evidence of three-dimensional (3D) critical fluctuations near Tc in B
doped Q-carbon. The crossover from 2D to 3D critical fluctuations is seen at T/Tc
= 1.01 as compared to T/Tc = 1.11 in conventional Bardeen-Cooper-Schrieffer (BCS)
high-temperature superconductors. These critical fluctuations indicate moderate
to strong electron-phonon coupling in B-doped Q-carbon. The isomagnetic
temperature-dependent resistivity measurements reveal a broadening of
superconducting transition width with increasing magnetic field. The upper
critical field (Hc2(0)) is calculated to be 5.6 T using the power law. Finally,
the superconducting region is determined in B-doped Q-carbon, as the three
vertices of the superconducting region are calculated as Tc = 36.0 K, Jc = 2.9 *
109 A cm-2 and Hc2 = 5.6 T. The temperature-dependent magnetic moment and
resistivity measurements also validate B-doped Q-carbon as a BCS type-II
superconductor. B concentration in Q-carbon can be increased up to 50 at% by a
nanosecond laser melting and quenching technique, thus providing an ideal
platform for near room-temperature superconductivity.
PMID- 29946613
TI - Synthesis of N-arylsulfonamides via Fe-promoted reaction of sulfonyl halides with
nitroarenes in an aqueous medium.
AB - A fascinating Fe-promoted protocol for the synthesis of N-arylsulfonamides has
been developed. Starting from commercially available nitroarenes and sulfonyl
chlorides, moderate to excellent yields of the corresponding N-arylsulfonamides
can be obtained. In particular, Fe dust serves as the sole reductant in the
transformation and it can be easily performed on a large scale.
PMID- 29946614
TI - Correction: Covalent layer-by-layer films: chemistry, design, and
multidisciplinary applications.
AB - Correction for 'Covalent layer-by-layer films: chemistry, design, and
multidisciplinary applications' by Qi An et al., Chem. Soc. Rev., 2018, DOI:
10.1039/c7cs00406k.
PMID- 29946615
TI - Charge designable and tunable GFP as a target pH-responsive carrier for
intracellular functional protein delivery and tracing.
AB - A charge designable and tunable green fluorescent protein (GFP)-based protein
delivery strategy was proposed. The acquired His29GFP selectively permeates the
cell membrane at a target pH of 6.5 and escapes from the endosome efficiently.
The delivered RNase A caused substantial mRNA degradation in HeLa cells, and
proliferation inhibition in different cell lines and a 3D tumor model at pH 6.5.
PMID- 29946616
TI - A high-throughput multi-microfluidic crystal generator (MMicroCryGen) platform
for facile screening of polymorphism and crystal morphology for pharmaceutical
compounds.
AB - In this work, a novel multi-microfluidic crystallization platform called
MMicroCryGen is presented, offering a facile methodology for generating
individual crystals for fast and easy screening of the polymorphism and crystal
habit of solid compounds. The MMicroCryGen device is capable of performing 8 * 10
cooling crystallization experiments in parallel using 8 disposable microcapillary
film strips, each requiring less than 25 MUL of solution. Compared to traditional
microfluidic systems, the MMicroCryGen platform does not require complex fluid
handling; it can be directly integrated with a 96-well microplate and it can also
work in a "dipstick" mode. The produced crystals can be safely and directly
observed inside the capillaries by optical and spectroscopic techniques. The
platform was validated by performing a number of independent experimental runs
for: (1) polymorph and hydrate screening of ortho-aminobenzoic acid, succinic
acid and piroxicam; (2) co-crystal form screening of the p
toluenesulfonamide/triphenylphosphine oxide system; (3) studying the effect of o
toluic acid on ortho-aminobenzoic cooling crystallization (effect of structurally
related additives). In all three cases, all known solid forms were identified
with a single experiment using ~200 MUL of solvent and just a few micrograms of
the solid material. The MMicroCryGen is simple to use, inexpensive and it
provides increased flexibility compared to traditional crystallization
techniques, being an effective new microfluidic solution for solid form screening
in pharmaceutical, fine chemicals, food and agrochemical industries.
PMID- 29946617
TI - Facile and practical synthesis of beta-carbolinium salts and gamma-carbolinium
salts via rhodium-catalyzed three-component reactions.
AB - A facile and practical [Cp*RhCl2]2-catalyzed three-component reaction between
indolyl aldehydes, amines and alkynes involving C-H activation and cyclization
has been developed. A series of beta-carbolinium salts and gamma-carbolinium
salts are successfully afforded in good to quantitative yields under mild
conditions. This efficient and convergent strategy provides a good choice for
constructing the libraries of beta-carbolinium salts and gamma-carbolinium salts.
PMID- 29946618
TI - Sensitized photon upconversion in anthracene-based zirconium metal-organic
frameworks.
AB - Sensitized upconversion is explored in three metal-organic frameworks (MOFs)
constructed from the anthracene dicarboxylate (ADC) derivatives and zirconium
nodes, 9,10-ADC (9,10-MOF), 2,6-ADC (2,6-MOF) and 1,4-ADC (1,4-MOF). Selective
excitation of surface-bound Pd(ii) mesoporphyrin IX (PdMP) gives rise to delayed
fluorescence (tau = 370 +/- 30 ns) from anthracene in the 9,10-MOF. The overall
upconversion efficiency of the Pd@9,10-MOF is 0.46 +/- 0.05% with a threshold
intensity of 104 +/- 26 mW cm-2.
PMID- 29946619
TI - Probing the influence of cell surface polysaccharides on nanodendrimer binding to
Gram-negative and Gram-positive bacteria using single-nanoparticle force
spectroscopy.
AB - The safe use and design of nanoparticles (NPs) ask for a comprehensive
interpretation of their potentially adverse effects on (micro)organisms. In this
respect, the prior assessment of the interactions experienced by NPs in the
vicinity of - and in contact with - complex biological surfaces is mandatory. It
requires the development of suitable techniques for deciphering the processes
that govern nano-bio interactions when a single organism is exposed to an
extremely low dose of NPs. Here, we used atomic force spectroscopy (AFM)-based
force measurements to investigate at the nanoscale the interactions between
carboxylate-terminated polyamidoamine (PAMAM) nanodendrimers (radius ca. 4.5 nm)
and two bacteria with very distinct surface properties, Escherichia coli and
Lactococcus lactis. The zwitterionic nanodendrimers exhibit a negative peripheral
surface charge and/or a positive intraparticulate core depending on the solution
pH and salt concentration. Following an original strategy according to which a
single dendrimer NP is grafted at the very apex of the AFM tip, the density and
localization of NP binding sites are probed at the surface of E. coli and L.
lactis mutants expressing different cell surface structures (presence/absence of
the O-antigen of the lipopolysaccharides (LPS) or of a polysaccharide pellicle).
In line with electrokinetic analysis, AFM force measurements evidence that
adhesion of NPs onto pellicle-decorated L. lactis is governed by their underlying
electrostatic interactions as controlled by the pH-dependent charge of the
peripheral and internal NP components, and the negatively-charged cell surface.
In contrast, the presence of the O-antigen on E. coli systematically suppresses
the adhesion of nanodendrimers onto cells, may the apparent NP surface charge be
determined by the peripheral carboxylate groups or by the internal amine
functions. Altogether, this work highlights the differentiated roles played by
surface polysaccharides in mediating NP attachment to Gram-positive and Gram
negative bacteria. It further demonstrates that the assessment of NP bioadhesion
features requires a critical analysis of the electrostatic contributions stemming
from the various structures composing the stratified cell envelope, and those
originating from the bulk and surface NP components. The joint use of
electrokinetics and AFM provides a valuable option for rapidly addressing the
binding propensity of NPs to microorganisms, as urgently needed in NP risk
assessments.
PMID- 29946621
TI - A guard to reduce the accidental oxidation of PbTe nanocrystals.
AB - In the synthesis of lead telluride nanocrystals (PbTe NCs), oxidized PbTe is
commonly regarded as a waste material as this will reduce the performance of pure
PbTe NCs. The waste is normally thrown away, leading to potential environment
risks and is less economical in terms of atom usage. Conventional anti-oxidation
methods such as inert gas flow or sealed systems cannot deal with leaking or
accidental contamination. To solve this problem, by simulating accidental
oxidation, we utilized a cheap and easily-performed strategy to reduce the
oxidation to a very low level. Further analysis indicates that this anti
oxidation effect should be due to interactions between the double bonds from the
coating ligands and the extended pi bonds from the benzene rings. This strategy
increases the synthesis efficiency of the reactants and reduces the environmental
pollution risk.
PMID- 29946620
TI - Direct synthesis of graphene on silicon oxide by low temperature plasma enhanced
chemical vapor deposition.
AB - Direct graphene growth on silicon with a native oxide using plasma enhanced
chemical vapour deposition at low temperatures [550 degrees C-650 degrees C] is
demonstrated for the first time. It is shown that the fine-tuning of a two-step
synthesis with gas mixtures C2H2/H2 yields monolayer and few layer graphene films
with a controllable domain size from 50 nm to more than 300 nm and the sheet
resistance ranging from 8 kOmega sq-1 to less than 1.8 kOmega sq-1. Differences
are understood in terms of the interaction of the plasma species - chiefly atomic
H - with the deposited graphene and the native oxide layer. The proposed low
temperature direct synthesis on an insulating substrate does not require any
transfer processes and improves the compatibility with the current industrial
processes.
PMID- 29946622
TI - Effect of the metal-support interaction on the activity and selectivity of
methanol oxidation over Au supported on mesoporous oxides.
AB - To elucidate the factors affecting the catalytic properties of supported Au
catalysts on the metal oxide support we investigated Au NPs deposited on
crystallized mesoporous transition-metal oxides (m-oxides: Co3O4, NiO, and alpha
Fe2O3) prepared using the nanocasting method. The metal-oxide interaction in
Au/mesoporous oxides resulted in higher catalytic activity for converting
methanol to CO2 as a full oxidation product than pure m-oxides. Au/m-Fe2O3
exhibited high activity and low selectivity for methyl formate as a partial
oxidative coupling product. We correlate the change in activity and selectivity
with the interface between the Au and m-oxides.
PMID- 29946623
TI - Radiation damage during in situ electron microscopy of DNA-mediated nanoparticle
assemblies in solution.
AB - Oligonucleotide-nanoparticle conjugates, also called programmable atom
equivalents, carry promise as building blocks for self-assembled colloidal
crystals, reconfigurable or stimuli responsive functional materials, as well as
bio-inspired hierarchical architectures in wet environments. In situ studies of
the DNA-mediated self-assembly of nanoparticles have so far been limited to
reciprocal space techniques. Liquid-cell electron microscopy could enable imaging
such systems with high resolution in their native environment but to realize this
potential, radiation damage to the oligonucleotide linkages needs to be
understood and conditions for damage-free electron microscopy identified. Here,
we analyze in situ observations of DNA-linked two-dimensional nanoparticle
arrays, along with control experiments for different oligonucleotide
configurations, to identify the mechanisms of radiation damage for ordered
superlattices of DNA-nanoparticle conjugates. In a biological context, the
results point to new avenues for studying direct and indirect radiation effects
for small ensembles of DNA in solution by tracking conjugated nanoparticles. By
establishing low-dose conditions suitable for extended in situ imaging of
programmable atom equivalents, our work paves the way for real-space observations
of DNA-mediated self-assembly processes.
PMID- 29946624
TI - Microfluidic nozzle device for ultrafine fiber solution blow spinning with
precise diameter control.
AB - We present a microfluidic nozzle device for the controlled continuous solution
blow spinning of ultrafine fibers. The device is fabricated by soft lithography
techniques and is based on the principle of a gas dynamic virtual nozzle for
precise three-dimensional gas focusing of the spinning solution. Uniform fibers
with virtually endless length can be produced in a continuous process while
having accurate control over the fiber diameter. The nozzle device is used to
produce ultrafine fibers of perfluorinated copolymers and of polycaprolactone,
which are collected and drawn on a rotating cylinder. Hydrodynamics and mass
balance quantitatively predict the fiber diameter, which is only a function of
flow rate and air pressure, with a small correction accounting for viscous
dissipation during jet formation, which slightly reduces the jet velocity.
Because of the simplicity of the setup, the precise control of the fiber
diameter, the positional stability of the exiting ultrafine fiber and the
potential to implement arrays of parallel channels for high throughput, this
methodology offers significant benefits compared to existing solution-based fiber
production methods.
PMID- 29946625
TI - Rhodium-catalyzed asymmetric synthesis of beta-branched esters from allylic
amines.
AB - Allylic amines are converted to chiral, beta-branched esters under rhodium
catalysis in the presence of alcohol nucleophiles. Allylic amines with aliphatic
and aromatic vinylic substituents are converted to ester products with excellent
enantioselectivities in all cases. Several alcohol nucleophiles have been
utilized in the reaction including 1 degrees and 2 degrees derivatives.
PMID- 29946626
TI - Ultrafast, asymmetric charge transfer and slow charge recombination in
porphyrin/CNT composites demonstrated by time-domain atomistic simulation.
AB - The versatile photochemical properties of porphyrin molecules make them excellent
candidates for solar energy applications. Carbon nanotubes (CNTs) exhibit
superior charge conductivity and have been combined with porphyrins to achieve
efficient and ultrafast charge separation. Experiments show that the charge
separated state lives less than 10 ps, which is too short for applications. Using
real-time time-dependent tight binding density functional theory (DFTB) combined
with non-adiabatic molecular dynamics (NAMD), we model photo-induced charge
separation and recombination in two porphyrin/CNT composites. Having achieved
excellent agreement with the experiment for the electron transfer from the
porphyrins to the CNT, we demonstrate that hole transfer can be achieved upon CNT
excitation, although in a less efficient way. By exciting the CNT one can extend
light harvesting into lower energies of the solar spectrum and increase solar
light conversion efficiency. We also show that the charge separated state can
live over 1 ns. The two orders of magnitude difference from the experimental
lifetime could arise due to the presence of defects or metallic tubes in the
samples. The charge separated state is long-lived because the non-adiabatic
electron-phonon coupling is very small, less than 1 meV, and the quantum
coherence is short, 15-20 fs. The excited states in the isolated porphyrins and
CNT live around 100 ps, in agreement with experiments as well. The porphyrin/CNT
interaction occurs through the pi-electron systems of the two species. The non
radiative relaxation is promoted by both high and low frequency phonons, with
higher frequency phonons playing more important roles in electron relaxation than
in hole relaxation. Low frequency phonons contribute significantly to the decay
of the charge separated state, because they modulate the relative positions of
the porphyrins and the CNT. The time-domain atomistic simulations provide a
detailed understanding of the charge separation and recombination mechanisms, and
generate valuable guidelines for the optimization of photovoltaic efficiency in
modern nanoscale materials.
PMID- 29946627
TI - Iron(ii) complexes of tris(2-pyridylmethyl)amine (TPMA) and neutral bidentate
ligands showing thermal- and photo-induced spin crossover.
AB - Three new mononuclear Fe(ii) complexes have been prepared and characterized by
the combination of tetradentate tris(2-pyridylmethyl)amine (TPMA) with three
neutral bidentate ligands, such as ethylenediamine (en), 1,2-diaminopropane (pn)
and 2-picolylamine (2-pic), in compounds [FeII(TPMA)(en)](ClO4)2 (1),
[FeII(TPMA)(2-pic)](ClO4)2 (2) and [FeII(TPMA)(pn)](ClO4)2 (3). Structural and
magnetic characterization demonstrates that the three compounds present a
complete SCO behavior. The absence of strong intermolecular interactions and
solvent molecules leads to reversible and gradual spin transitions. The different
ligands allow tuning T1/2 from 130 K (2) to 325 K (3). The compound with the
lowest T1/2 (2) shows the LIESST effect with a TLIESST of 43 K. Interestingly,
the use of these relatively small bidentate ligands leads to the crystallization
in non-centrosymmetric space groups in contrast with previous studies using other
bidentate ligands.
PMID- 29946628
TI - Native DNA electronics: is it a matter of nanoscale assembly?
AB - The genomic DNA is enveloped by nanotubes formed by the nuclear aggregates of
polyamines (NAPs) that induce DNA conformational changes and provide protection
and increased interaction abilities for the double strands. In a physiological
environment, the nanotube arrangement is initiated by spontaneous interaction
among the terminal amino groups of the polyamines and the phosphate ions, with
the consequent formation of cyclic monomers that hook at the DNA grooves. The
polymer thus formed has the morphological features of an organic semiconductor
and therefore, it can be considered to be able to conduct electric charges.
Phosphate ions positioned on the NAP external surface could regulate, as in a
physical electric circuit, both linear and rotational (histones) protein motion,
in accordance with the basilar principles of the electronics. A model of a
carrier system for protein motion along the polymer wrapping the DNA strands,
based on the phosphate-phosphate complexation, is proposed.
PMID- 29946629
TI - Elastic capsules at liquid-liquid interfaces.
AB - We investigate the deformation of elastic microcapsules adsorbed at liquid-liquid
interfaces. An initially spherical elastic capsule at a liquid-liquid interface
undergoes circumferential stretching due to the liquid-liquid surface tension and
becomes lens- or discus-shaped, depending on its bending rigidity. The resulting
elastic capsule deformation is qualitatively similar, but distinct from the
deformation of a liquid droplet into a liquid lens at a liquid-liquid interface.
We discuss the deformed shapes of droplets and capsules adsorbed at liquid-liquid
interfaces for a whole range of different surface elasticities: from droplets
(only surface tension) deforming into liquid lenses, droplets with a Hookean
membrane (finite stretching modulus, zero bending modulus) deforming into elastic
lenses, to microcapsules (finite stretching and bending modulus) deforming into
rounded elastic lenses. We calculate capsule shapes at liquid-liquid interfaces
numerically using shape equations from nonlinear elastic shell theory. Finally,
we present theoretical results for the contact angle (or the capsule height) and
the maximal capsule curvature at the three phase contact line. These results can
be used to infer information about the elastic moduli from optical measurements.
During capsule deformation into a lens-like shape, surface energy of the liquid
liquid interface is converted into elastic energy of the capsule shell giving
rise to an overall adsorption energy gain by deformation. Soft hollow capsules
exhibit a pronounced increase of the adsorption energy as compared to filled soft
particles and, thus, are attractive candidates as foam and emulsion stabilizers.
PMID- 29946630
TI - Effect of boron doping on the electrical conductivity of metallicity-separated
single walled carbon nanotubes.
AB - We explored the effect of substitutional boron doping on the electrical
conductivity of a metallicity-separated single walled carbon nanotube (SWCNT)
assembly. Boron atoms were introduced into semiconducting (S)- and metallic (M)
SWCNT assemblies using high temperature thermal diffusion and the concentration
of the doped boron atoms was controlled by the thermal treatment temperature.
Depending on the conduction mechanism of the SWCNT assembly, both positive and
negative effects upon boron incorporation are observed. For the S-SWCNT sheet,
the electrical resistivity decreased by about 1 order on introduction of a small
amount of boron atoms, due to the localized state for hopping conduction. In
contrast, we observed an increase in the electrical resistivity on boron doping
for M-SWCNTs. The pristine and boron doped metallic SWCNTs exhibited a tendency
of decreasing electrical resistivity in the presence of an external magnetic
field perpendicular to the film, which indicated two-dimensional weak
localization behavior. A detailed analysis of the resistivity and the
magnetoresistance implied that an increase in the inelastic scattering event at
the doped boron site reduced the phase coherence length, leading to an increase
in the electrical resistivity.
PMID- 29946631
TI - [Effects of Porphyromonas endodontalis lipopolysaccharides on the expression of
monocyte chemotactic protein-1 in mouse osteoblasts].
AB - PURPOSE: To investigate the effects of lipopolysaccharide (LPS) extracted from
Porphyromonas endodontalis (P.endodontalis) on expression of monocyte chemotactic
protein-1 (MCP-1) mRNA and protein in MC3T3-E1 cells and the role of p38 mitogen
activated protein kinase (MAPK) and nuclear factor-kB(NF-kB)in the process.
METHODS: MC3T3-E1 cells were treated with different concentrations of
P.endodontalis LPS(0-50mg/L) and 20 mg/L P.endodontalis LPS for different hours
(0-48 h). The expression of MCP-1 mRNA was detected by real-time reverse
transcription PCR(RT-PCR) and protein was detected by enzyme-1inked immunosorbent
assay (ELISA). MC3T3-E1 cells were pretreated with SB203580 (inhibitor of
p38MAPK) and BAY11-7082 (inhibitor of NF-kB) for 1h, and then were treated with
20 mg/L P.endodontalis LPS for 24 h, the expression of MCP-1 mRNA was also
detected by RT-PCR. Statistical analysis was performed using one-way ANOVA and
Dunnett t test with SPSS 13.0 software package. RESULTS: The level of MCP-1 mRNA
and protein increased significantly after treatment with different concentrations
of P.endodontalis LPS (0-50 mg/L), which indicated that P.endodontalis LPS
induced osteoblasts to express MCP-1 in a dose dependent manners. During the
observation time (0-48 h), the impact of 20 mg/L P.endodontalis LPS on induction
of MCP-1 in MC3T3-E1 cells exhibited a time-dependent manner. The expression of
MCP-1 mRNA decreased significantly after pretreated with 10 mol/L SB203580 and
BAY11-7082 for 1 h,and the inhibitory effect of SB203580 was stronger than BAY11
7082. CONCLUSIONS: P.endodontalis LPS may induce the expression of MCP-1 mRNA and
protein in MC3T3-E1 cells through the signaling pathway of p38MAPK and NF-kB.
PMID- 29946632
TI - [Micro-CT study of root canal morphology of mandibular first premolars with multi
canals].
AB - PURPOSE: To observe root canal system of multi-canal mandibular first premolars
and to analyze the morphology of them by micro-CT and three-dimensional
reconstruction. METHODS: Thirty-two extracted mandibular first premolars with
multiple root canals were selected and scanned by micro-CT. The number and
morphology of canals, location of bifurcation and 5 subtle structures (lateral
canals, apical ramification, isthmus, loops, apical delta) were analyzed.
RESULTS: In the 32 specimens, 96.88% contained radicular depressions or grooves.
The canal configuration was type II, III, V: 3.12%, type IV: 31.25%, type VIII:
9.38%, type IX: 15.62% and C-shaped canal: 34.38% by Vertucci's classification.
62.50% of the canals bifurcated at the middle third of roots, comparing with
37.50% at apical third. The incidence of the lateral canals, apical ramification,
isthmus, loops and apical delta was 56.25%, 43.75%, 40.62%, 21.88% and 6.25%,
respectively, which were all found at the middle and apical third of roots except
that lateral canals were found at all depth of canals. CONCLUSIONS: Most
mandibular first premolars with multiple canals contain radicular depression or
grooves, of which root canal system are complicated. Micro-CT can provide clear
and accurate three-dimensional information of canal morphology.
PMID- 29946633
TI - [MicroRNA-125b regulates osteogenic differentiation of human periodontal ligament
stem cells].
AB - PURPOSE: To investigate the effect of microRNA-125b (miR-125b) on osteogenic
differentiation of periodontal ligament stem cell (PDLSCs). METHODS: The surface
factor of isolated PDLSCs was detected by flow cytometry. After transfected with
miR-125b or anti-miR125b in PDLSCs, MTT and LDH were used to detect cell
viability and cytotoxicity; ALP activity and calcium level were detected by ALP
assay kit and calcium colorimetric assay kit. Western blot and RT-qPCR were used
to determine the expression of osteogenesis-related genes. The interaction
between miR-125b and connexin 43 (Cx43) was detected by dual luciferase gene
reporter assay. The data were analyzed with SPSS 17.0 software. RESULTS: The
cultured PDLSCs showed the characteristics of mesenchymal stem cells. After
transfected with miR-125b in PDLSCs, the cell viability was decreased,
cytotoxicity was increased; ALP activity, calcium level and the expression of
osteogenesis-related genes were significantly decreased. On the contrary, cell
viability, ALP activity, calcium level and the expression of osteogenesis-related
genes in PDLSCs were increased after anti-miR-125b transfection. Dual luciferase
gene reporter assay showed that miR-125b could target Cx43. In addition, the
effect of miR-125b on osteogenic differentiation of PDLSCs was reversed after
Cx43 overexpression. CONCLUSIONS: miR-125b may inhibit osteogenic differentiation
of PDLSCs by targeting Cx43.
PMID- 29946634
TI - [Expression of vascular endothelial growth factor in periodontal tissues during
orthodontic tooth movement and its role in bone remodeling].
AB - PURPOSE: To investigate the expression of VEGF in periodontal tissues and its
role in bone remodeling during orthodontic tooth movement in rats. METHODS: Rat
model of tooth movement was established, and 30 rats in the experimental group
were divided into 5 groups, 6 rats in each group. At 2 days, 4 days, 7 days, 14
days and 20 days, the rats were sacrificed to make periodontal tissue slice. The
morphological changes of periodontal tissue were observed under H-E staining, and
the expression of VEGF was semi-quantitatively analyzed by immunohistochemistry.
The data were analyzed using SPSS21.0 software package. RESULTS: Expression of
VEGF in normal rat periodontal tissues was very weak or without positive
expression; 2 days after tooth movement, VEGF expression in periodontal tissues
began to increase from seventh to fourteenth days; on the fourteenth day, the
expression reached a peak; after twentieth day, the expression of VEGF decreased
slightly, but still higher than the control group. The expression of VEGF was
mainly found in the cytoplasm of vascular endothelial cells, osteoblasts,
fibroblasts, and osteoclasts. CONCLUSIONS: Expression of VEGF may play an
important role in the early remodeling of periodontal tissues during orthodontic
tooth movement.
PMID- 29946635
TI - [Effect of overdose fluoride on the expression of TGF-beta3 in rat incisor].
AB - PURPOSE: To observe the effect of overdose fluoride on the expression of TGF
beta3 in rat incisor and to explore the possible mechanism of dental fluorosis.
METHODS: Twenty Wistar rats were randomly divided into 2 groups. The animals were
maintained in standard environmental conditions with free access to food and
water (control group) or water added with 100mg/L F (experimental group). The
rats were killed at the end of 8th week. The expression of TGF-beta3 was detected
by immunohistochemical staining. Statistical analysis was performed using
SPSS12.0 software package. RESULTS: The expression of TGF-beta3 in ameloblasts
was significantly inhibited in the experimental of group II(P<0.01). The gray
value of the control group and the fluorine group were 85.89+/-7.90, 116.76+/
8.04, respectively. CONCLUSIONS: Fluoride might disturb the signal transduction
between the epithelia and mesenchyma by inhibiting the expression of TGF-beta3 in
ameloblasts, which in turn may inhibit the differentiation and function of the
tooth-forming cells.
PMID- 29946636
TI - [Influences of filler content and size on the translucency parameter of resin
composites].
AB - PURPOSE: The objective of this study was to investigate the influences of filler
content and size on the translucency parameter of non-layered resin composites.
METHODS: Three types of fillers (0.7 MUm, 1.0 MUm and 1.5 MUm) were mixed at
weight contents of 60wt%, 70wt%, 75wt%, and 80wt%. The L*, a* and b* value was
analyzed based on CIELab color space of the specimen respectively on black and
white background. The results of each test were analyzed with one-way ANOVA
followed by Tukey's HSD test using SPSS 20.0 software package. RESULTS: For each
filler size, there was a trend of decreasing translucency parameter as the filler
content increased (P<0.05). The filler size did not affect the translucency
parameter of the composites in this study. CONCLUSIONS: When the fillers content
changed from 60wt% to 80wt%, there is a trend of decreasing translucency
parameter as the filler content increased, and the filler size may not influence
the translucency parameter of the composites when the size changed from 0.7 MUm
to 1.5 MUm.
PMID- 29946637
TI - [KLF5 modulates proliferation and osteogenic differentiation of human periodontal
ligament cells subjected to cyclic tensile stress].
AB - PURPOSE: To investigate the expression of Kruppel-like factor 5 (KLF5) in human
periodontal ligament cells (hPDLCs) under cyclic tensile stress (CTS) and its
effect on proliferation and osteogenic differentiation of hPDLCs. METHODS: hPDLCs
were primarily cultured in vitro by tissue explant and enzyme digestion method.
RT-PCR and Western blot were used to detect mRNA and protein expression of KLF5
in hPDLCs stimulated by 10% CTS at a frequency of 0.5 Hz for 1, 4, 8, 12 and 24
h, respectively.KLF5 was then knocked-down in hPDLCs using siRNA (si-KLF5) and
its mRNA expression was determined by RT-PCR. Meanwhile, basic fibroblast growth
factor (FGF2) was overexpressed in KLF-5 silenced hPDLCs by using pcDNA3.1-FGF2.
After stimulation with CTS for 8 h, the proliferation of hPDLCs was assayed by
CCK-8 kit, alkaline phosphatase (ALP) activity was assayed by ALP kit, the mRNA
expression of Runx2 and Osterix was examined by RT-PCR, and the protein
expression of Runx2, Osterix, FGF2, GSK-3beta, P-GSK-3beta (ser 9), beta-catenin
was determined by Western blot. The data were analyzed using SPSS 22.0 software
package. RESULTS: Stimulation with 10% CTS time-dependently induced mRNA and
protein expression of KLF5 in hPDLCs. Transfection of si-KLF5 significantly
reduced the proliferation of hPDLCs, decreased ALP activity and expression of
Runx2 and Osterix in hPDLCs stimulated by 10% CTS. Simultaneously, CTS-induced
activation of FGF2-GSK-3beta/beta-catenin signaling pathway was also inhibited by
si-KLF5 transfection. However, overexpression of FGF2 can partly neutralized the
inhibitiory effect of si-KLF5 on proliferation and osteogenic differentiation of
hPDLCs subjected to 10% CTS. CONCLUSIONS: KLF5 promotes proliferation and
osteogenesis differentiation of hPDLCs subjected to cyclic tensile stress through
FGF2-GSK-3beta/beta-catenin signaling pathway.
PMID- 29946638
TI - [Measurement of the mesiobuccal root canal width and taper of maxillary first
molars].
AB - PURPUSE: To measure the root canal morphology of the maxillary first molars, to
provide reference for clinical work. METHODS: Fifty maxillary first molars were
collected and the mesiobuccal root canal taper was observed through production of
transparent tooth. The mesiobuccal roots were dissected transversely from their
apical foramen vertical to the long axis of the root and 0.4-mm-thick serial
sections were made. Each section was observed with a stereomicroscope at 30*
magnification to calculate the taper value of apical 1/3, middle third 1/3 and
canal orifice 1/3. RESULTS: The width of MB1 root canal: maximum and minimum
diameter of root apex was (0.38+/-0.12) mm and (0.34+/-0.16) mm, maximum and
minimum diameter of root middle was (0.55+/-0.26) mm and (0.57+/-0.12) mm,
maximum and minimum diameter of root collar was (1.13+/-0.34) mm and (0.59+/
0.18) mm. The width of MB2 root canal taper: maximum and minimum diameter of root
apex was (0.25+/-0.13) mm and (0.28+/-0.10) mm, maximum and minimum diameter of
root middle was (0.36+/-0.09) mm and (0.17+/-0.06) mm, maximum and minimum
diameter of root collar was (0.79+/-0.23) mm and (0.23+/-0.17) mm. The taper of
MB1 root canal: maximum and minimum diameter of root apical 1/3 was 0.03 and
0.01, maximum and minimum diameter of root middle 1/3 was 0.06 and 0.03, maximum
and minimum diameter of root collar 1/3 was 0.10 and 0.09. The taper of MB2 root
canal: maximum and minimum diameter of root apical 1/3 was 0.02 and - 0.01,
maximum and minimum diameter of root middle 1/3 was 0.06 and 0.00, maximum and
minimum diameter of root collar 1/3 was -0.02 and -0.02. CONCLUSIONS: MB1 has a
larger width and taper, and root apical 1/3, middle 1/3, collar 1/3 have variable
taper; While the width and taper of MB2 are small, and there will be upside down
taper.
PMID- 29946639
TI - [Isolation, identification and biological characteristics of the stem cells from
mucoepidermoid carcinoma of the salivary gland].
AB - PURPOSE: To study the specific genes of mucoepidermoid carcinoma of mucus - like
cancer cells of the salivary gland, and to further understand the mechanism of
tumor stem cells. METHODS: Single cell culture of tumor cells was performed by
limited dilution method. The growth of tumor stem cells was observed. The
relative specific surface markers of salivary gland mucoepidermoid carcinoma stem
cells were determined by immunomagnetic separation technology. The data were
analyzed with SPSS 11.5 software package. RESULTS: The expression of CD133 was
higher in the M3SP2 cell line, and the high expression of CD133 was significantly
different(P<0.05). CONCLUSIONS: CD133 may be one of the surface specific antigen
markers of M3SP2 monoclonal cell lines in salivary gland mucoepidermoid carcinoma
cell line.
PMID- 29946640
TI - [Detection and significance of IL-6 and TNF-alpha in patients with Graves disease
and periodontitis].
AB - PURPOSE: To investigate the expression of IL-6 and TNF-alpha in gingival
crevicular fluid (GCF) and serum of patients with Graves' disease(GD) and
periodontitis (CP), and to analyze the correlation between Graves' disease and
periodontitis. METHODS: One hundred and twenty subjects were selected and divided
into 4 groups: 30 healthy participants as the control group, 30 patients with CP,
30 patients with GD, and 30 patients with GD and CP. The serum and GCF level of
IL-6 and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA),
and clinical periodontal parameters including probing depth (PD), clinical
attachment level (CAL) and sulcus bleeding indexes (SBI) were examined. The date
was analyzed with SPSS19.0 software package. RESULTS: The concentration of IL-6
and TNF-alpha in serum and GCF of patients with GD+CP group was significantly
higher than that in CP group and GD group (P<0.05). The level of IL-6 and TNF
alpha in serum and GCF of patients in GD+CP group and GD group was positively
correlated with FT3 and FT4 (P<0.05), and the correlation between GD+CP group was
significantly higher than that in GD group. CONCLUSIONS: The level of IL-6 and
TNF-alpha in GD+CP group were significantly higher than those in CP group and GD
group, indicating that there is an interaction between periodontitis and Graves'
disease in immune mechanism.
PMID- 29946641
TI - [Assessment of mental health status and plasma catecholamine levels in patients
with recurrent aphthous ulcer].
AB - PURPOSE: To investigate the relationship between mental health and recurrent
aphthous ulcer (RAU), and to explore the change of plasma catecholamine level in
RAU patients. METHODS: Thirty RAU patients treated in Nanjing Stomatological
Hospital, Medical School of Nanjing University from February 2016 to August 2016
were selected as the experimental group, and 30 healthy people with matched age
and gender were selected as the control group. Patients in both groups were asked
to fill in the psychological scales for researchers to analyze their mental
state, including Self-Rating Anxiety Scale (SAS) and Self-rating Depression Scale
(SDS). Whole blood samples were taken from the selected subjects around 9 am to
10 am. High performance liquid chromatography (HPLC) was used to analyze the
plasma catecholamine level. Statistical analysis was performed using SPSS 22.0
software package. RESULTS: The results of SAS and SDS showed that the standard
scores of the experimental group were significantly higher than those of the
control group (P<0.01), analysis of plasma catecholamine level showed that
adrenaline level in the experimental group was significantly higher than the
control group (P<0.01). Analysis of the plasma adrenaline level and standard
scores of both psychological scales showed that they had significant correlation.
CONCLUSIONS: There is a close relationship between the development of RAU and the
mental state of patients. Meanwhile, plasma adrenaline level significantly
increases in patients with RAU.
PMID- 29946642
TI - [A prospective study of changes in oral health-related quality of life during
"all-on-four" immediate restoration for edentulous individuals].
AB - PURPOSE: This clinical study was to evaluate oral health-related quality of life
(OHRQoL) changes in patients who underwent all-on-4 treatment in one or both
jaws. METHODS: Eleven patients underwent placement of 4 to 6 dental implants on
the basis of all-on-4 treatment concept in the maxilla, mandible or both jaws and
immediate loading with acrylic interim prostheses. The prostheses were replaced
after 3-6 months, and definitive prostheses with metal framework and reinforced
resin facing were fixed after another 3 months or more. The subjects completed
the shortened Chinese version of the Oral Health Impact Profile (OHIP-14) before
surgery (T0), 1 week after interim prostheses were placed (T1) and 3 months after
definitive prosthesis placement (T2). The data of 11 subjects were analyzed with
Wilcoxon signed-rank test using SPSS 13.0 software package. RESULTS: The total
OHIP-14 score significantly reduced only at T2 (P<0.05). "Functional limitation,"
"physical pain," "physical disability," and "psychological disability" scores
significantly decreased at T2, and "psychological discomfort" scores also
significantly dropped at T1. "Social disability" and "handicap" scores remained
unchanged throughout the treatment course. CONCLUSIONS: Fixed definitive
prostheses with metal framework are more effective in improving OHRQoL than fixed
acrylic prostheses during all-on-4 treatments.
PMID- 29946643
TI - [Changes of oral bacteria flora after wearing complete denture].
AB - PURPOSE: This study investigateed the influence of complete denture on oral
bacteria flora. METHODS: Bateria plaque samples in oral mucosa, saliva and
denture surfaces in 11 edentulous patients were collected, then the 16S rRNA gene
clone libraries were constructed. Pyrosequencing was used to analyze the 16S rRNA
gene V3~V4 regions, oral bacteria flora were classified and identified. RESULTS:
There were 64800 sequences in complete denture-wearing subjects, Streptococcus
mitis, Gemella haemolysans, Rothia mucilaginosa, Porphyromonas sp, Neisseria
zoodegmatis, Granulicatella elegans, Acinetobacter baumannii, Pseudomonas
citrinum, Granulicatella adiacens and Fusobacterium canifelinum were the
predominant species (37416 sequences). The species of denture tissue surface were
similar to these of buccal vestibule after wearing denture, and the species of
denture smooth surface were similar to these of tongue ventrum and the floor of
mouth. CONCLUSIONS: The effect of complete denture on oral flora is still
limited, and the composition of oral flora is influenced by many other factors.
PMID- 29946644
TI - [Comparison of clinical efficacy of CAD/CAM all -ceramic inlay and polymerid
porcelain inlay in restoration of posterior Class II cavity].
AB - PURPOSE: To compare the clinical efficacy of CAD/CAM all-ceramic inlay and
polymerid porcelain inlay in restoring Class II cavity of posterior teeth.
METHODS: Ninety-seven patients with 100 posterior teeth of ClassII cavity were
recruited in this randomized control trial; Among them, 50 patients were grouped
into CAD/CAM all-ceramic inlays and 47 patients were grouped into Ceramage
polymerid porcelain inlay. According to the modified USPHS criteria, the
incidence of postoperative sensitivity, prosthesis fracture, prosthesis falling
off, and edge coloration were evaluated 12 months and 24 months after
restoration. Chi-square test and Wilcoxon rank sum test were used for statistical
analysis using SPSS 13.0 software package. RESULTS: Restoration in the 2 groups
were successful, there was no significant difference at 12 months (P>0.05).
Postoperative sensitivity and the incidence of prosthesis falling off in both
groups were not significantly different (P>0.05); however, the number of
prosthesis fracture of the polymerid porcelain was lower than that of the CAD/CAM
all-ceramic inlays (P<0.05). The incidence of edge coloration of CAD/CAM all
ceramic inlays was lower than that of the polymerid porcelain at 24-month follow
up (P<0.05). CONCLUSIONS: Restoration with polymerid porcelain is more likely to
have a higher success rate than those with CAD/CAM all-ceramic inlays. Patients
undergoing CAD/CAM all-ceramic inlays have a lower incidence of edge coloration,
compared with those undergoing polymerid porcelain.
PMID- 29946645
TI - [Evaluation of the effectiveness of cold-light whitening technique on
tetracycline pigmentation teeth and aged extrinsic stain teeth].
AB - PURPOSE: To evaluate the clinical effectiveness of cold-light whitening technique
on tetracycline pigmentation teeth and aged extrinsic stain teeth. METHODS: One
hundred and fifty-two cases bleached by cold-light whitening technique were
included in this study. The patients' teeth were divided into 3 groups: aged
extrinsic stain teeth, mild tetracycline pigmentation teeth and moderate
tetracycline pigmentation teeth. Visual determination of shade and Olympus
crystaleye spectrophotometer were used to measure the tooth discoloration after
bleaching. SPSS17.0 software package was used for statistical analysis. RESULTS:
Visual determination showed that the efficiency of aged extrinsic stain teeth was
significantly higher than that of mild and moderate tetracycline teeth group
(P<0.05). Colorimetric method showed that the ?E of moderate tetracycline teeth
was significantly lower than aged extrinsic teeth and mild tetracycline teeth
(P<0.05) . The ?E of cervix changed more significantly than that of central and
incisal edge in both mild and moderate tetracycline teeth group (P<0.05).
CONCLUSIONS: The effect of cold-light whitening technique on aged extrinsic stain
teeth is better than that of the tetracycline pigmentation teeth. Cold-light
whitening technique can improve pigmentation of tetracycline teeth cervix..
PMID- 29946646
TI - [Clinical evaluations of transitional treatment of pulpitis during pregnancy in
60 female patients].
AB - PURPOSE: The present study was aimed to clinically evaluate transitional
treatment of pulpitis during pregnancy. METHODS: Sixty pregnant women with
pulpitis were divided into the first, second and third trimester. They were
anesthetized locally using STA system combined with psychological intervention
during treatment. The teeth were given one-appointment root canal preparation and
filled with vitapex pasta. Normal obturation of the root canal was conducted
after delivery. The effects of dental treatment, pregnancy outcomes and neonatal
health status were observed. Data of the survey were analyzed by SPSS 20.0
software package, including Student's t test and chi-square test. RESULTS: The
symptoms of pulpitis were significantly improved 24h after treatment,and the
effective rate was 96.7%. The difference of VAS before and after treatment was
statistically significant (P<0.05). Patients had no discomfort till the end of
pregnancy,and the success rate was 98.3%. No adverse pregnancy outcomes were
observed after treatment during different periods of pregnancy. Neonatal health
was good. Significant differences were not found in birth gestational age, body
weight, malformations, and neonatal complications between three treatment periods
(P>0.05). CONCLUSIONS: Transitional treatment of pulpitis during pregnancy is a
safe and effective procedure and worthy of wide use clinically.
PMID- 29946647
TI - [The value of ultrasonic elastography in diagnosis of salivary gland lesions in
patients with Sjogren's syndrome].
AB - PURPOSE: The present study was aimed to clinically evaluate transitional
treatment of pulpitis during pregnancy. METHODS: Sixty pregnant women with
pulpitis were divided into the first, second and third trimester. They were
anesthetized locally using STA system combined with psychological intervention
during treatment. The teeth were given one-appointment root canal preparation and
filled with vitapex pasta. Normal obturation of the root canal was conducted
after delivery. The effects of dental treatment, pregnancy outcomes and neonatal
health status were observed. Data of the survey were analyzed by SPSS 20.0
software package, including Student's t test and chi-square test. RESULTS: The
symptoms of pulpitis were significantly improved 24h after treatment,and the
effective rate was 96.7%. The difference of VAS before and after treatment was
statistically significant (P<0.05). Patients had no discomfort till the end of
pregnancy,and the success rate was 98.3%. No adverse pregnancy outcomes were
observed after treatment during different periods of pregnancy. Neonatal health
was good. Significant differences were not found in birth gestational age, body
weight, malformations, and neonatal complications between three treatment periods
(P>0.05). CONCLUSIONS: Transitional treatment of pulpitis during pregnancy is a
safe and effective procedure and worthy of wide use clinically.
PMID- 29946648
TI - [A study on effects of unilateral maxillary canine impaction on the dento
maxillofacial three-dimensional structure].
AB - PURPOSE: To investigate the three-dimensional structure characteristics of
unilateral impacted teeth by cone-beam CT (CBCT), and to evaluate the risk
factors for upper impacted teeth, so as to provide evidence for early clinical
intervention in orthodontics. METHODS: Thirty patients with unilateral maxillary
canine impaction were included. Their CBCT images were measured by three
dimensional reconstruction of Romexis software. The differences of the three
dimensional structure characteristics between two sides were measured and
compared with SPSS17.0 software package. Paired t test and regression analysis of
related data were performed. RESULTS: Significant difference in inclination of
both canine and lateral incisor was found between impacted side and normal
eruption side, with canine mesially inclined and lateral incisor distally
inclined (P<0.001). Volumes of the canines were significantly bigger and those of
the lateral incisor were significantly smaller on the impacted side compared with
the normal eruption side (P<0.05). The occurrence of impacted canine increased
with the increase of the volume of the canine and decrease of the volume of the
lateral incisor. Significant difference in arch length and arch width in canine
and premolar area was found between impacted side and normal eruption side
(P<0.001). There was no significant difference in width in molar area between
both sides(P>0.05). There was no significant difference in arch length in canine,
premolar and molar region (P>0.05). CONCLUSIONS: Maxillary impacted canines can
lead to three-dimensional abnormalities of the ipsilateral teeth and alveolar
bone, the severity of maxillary impacted canine is closely related to surrounding
dental structural abnormalities, suggesting that maxillary impacted canines can
be predicted, early diagnosed, and early effectively intervened as well.
PMID- 29946649
TI - [Effect of dexmedetomidine combined with sevoflurane for general anesthesia
during dental treatment in pediatric patients].
AB - PURPOSE: To evaluate the effect of dexmedetomidine combined with sevoflurane for
general anesthesia during dental treatment in pediatric patients. METHODS: One
hundred and twenty pediatric patients undergoing dental treatment were randomly
divided into sevoflurane combined dexmedetomidine group(D group)and sevoflurane
group (S group), 60 children in each group. Children in group D inhaled 4%-6%
sevoflurane and intravenously received fentanyl 1 MUg/kg, midazolam 0.1 mg,
propofol 2 mg/kg, rocuronium 0.3 mg/kg, then tracheal intubation was performed
when eyelash reflex disappeared, the density of sevoflurane was reduced to 2%-3%
for maintenance. When the treatment started, 9-12 mg/(kg.h) of propofol was
pumped, and 1 MUg/kg of dexmedetomidine was pumped for 15 minutes, then the dose
was reduced to 0.5 MUg/(kg.h) until the end of treatment. Children in group S
didn't receive dexmedetomidine pumped. During the procedure, HR, MAP, and Ramsay
scale were recorded at baseline (T1), loss of eyelash reflex (T2), after
dexmedetomidine was pumped for 10 mins (T3), operation initiation (T4) and the
end of operation (T5). The operation time, recover and extubation time, pediatric
anesthesia emergence delirium scale (PAED) in pediatric anesthesia care unit
(PACU) were recorded. SPSS 20.0 software package was used for statistical
analysis. RESULTS: There was no significant difference in operation time between
the two groups. At T3-T5, MAP and HR were significantly lower, but Ramsay scale
was significantly higher in group D than in group S (P<0.05). The recover and
extubation time were significantly longer in group D (P<0.05). In PACU, PAED
scale was significantly lower in group D than in group S (P<0.05). CONCLUSIONS:
Dexmedetomidine combined with sevoflurane not only stabilize hemodynamic
parameters, but also reduce the impact on respiration during dental treatment in
pediatric patients.
PMID- 29946650
TI - [Clinical observation of the efficacy of Hybrid coat combined with composite
resin for restoring hypersensitive wedge-shaped defect].
AB - PURPOSE: The purpose of this study was to explore the effect of Hybrid-coat
combined with composite resin filling on reducing hypersensitivity of dental
wedge-shaped defect. METHODS: Seventy cases, 159 teeth with sensitive wedge
shaped defects were selected. The patients were randomly divided into 2 groups
and treated as below: 35 cases, 81 teeth in group A were treated with Hybrid-coat
combined with composite resin; 35 cases,78 teeth in group B were treated with
composite resin directly. After treatments, the effective rates under clinical
examination standard (immediately, 1, 3 and 6 months after filling) in both
groups were collected and statistically analysed with SPSS 13.0 software package.
RESULTS: In group A, one and 2 teeth fillings fell off 3 months and 6 months
after treatments ,respectively. In group B, 2 teeth fillings fell off 6 months
after operation. There was no significant difference between the two groups. The
effective rate of desensitization was 91.36%, 88.89%, 79.01% and 70.37%,
respectively, which was higher than those of group B (78.21%, 76.92%, 69.23% and
61.54%, respectively). There was significant difference between the two groups
immediately and 1 months after treatment (P<0.05), but there was no significant
difference between the two groups 3 months and 6 months after treatment.
CONCLUSIONS: Hybrid-coat combined with composite resin is effective in reducing
sensitivity of wedge-shaped defects.
PMID- 29946651
TI - [Evaluation of the effect of concentrated growth factor in oral rehabilitation].
AB - PURPOSE: To investigate the clinical effect of concentrated growth factor (CGF)
in oral cavity repair. METHODS: From February 2013 to February 2016 in our
hospital, 60 patients with insufficient bone underwent dental implantation. CGF
was used alone in 27 patients (CGF group), CGF was used with autologous bone or
bone material in 33 patients (CGF mixed group). Bone repair was observed and
evaluated. SPSS19.0 software package was used for statistical analysis. RESULTS:
Wound healing time in CGF group and CGF mixed group (8.43+/-0.72) d and (8.04+/
0.98) d, wound healing rate was 92.60% in CGF group and 90.91% in CGF group, the
difference was not statistically significant (P>0.05); Implant success rate in
CGF group and CGF mixed group was 92.31% and 96.36% , respectively. The
difference was not statistically significant (P>0.05). CONCLUSIONS: CGF has good
effect in repair of bone defect, and the long-term effect is stable. It is a
simple and safe material for bone regeneration.
PMID- 29946652
TI - [Clinical analysis of muscle function intensifier in treatment of 40 patients
with maxillary protrusion].
AB - PURPOSE: To investigate the clinical effects of combined muscle functions
intensifier and straight wire appliance in the treatment of maxillary protrusion.
METHODS: Forty patients with maxillary protrusion were randomly divided into 2
groups (group A and group B). Straight wire appliance and muscle function
intensifier were used in group A, while patients in group B received straight
wire appliance only. X-ray projection was conducted to measure relative maxillary
index (labial inclination of upper or lower incisor, SNB angle, ANB angle, FMA,
maxillary plane angle, NA-PA, U1-FH, U1-PP, forward moving distance of U6) before
and 6 months after treatment. The efficacy was analyzed and evaluated using SPSS
20.0 software package. RESULTS: After correction, labial inclination of upper or
lower incisor, SNB angle, ANB angle, FMA, maxillary plane angle, NA-PA, U1-FH, U1
PP changed significantly in both groups (P<0.05), but patients in group A
achieved more incisor adduction and less forward moving distance of U6, with
significant difference between the two groups (P<0.05). CONCLUSIONS: Most
patients with maxillary protrusion have a bad habit of mouth breathing. Muscle
function intensifier is used only at night and can relieve the patient's mouth
breathing, speed up the movement of teeth, and reduce the loss of anchorage and
ultimately, improve the correction efficiency and clinical effect of patients
with maxillary protrusion.
PMID- 29946653
TI - [Clinicopathological and prognostic significance of PD-L1 expression in oral
squamous cell carcinoma: a meta analysis].
AB - PURPOSE: To determine the prognostic role of high PD-L1 in patients with oral
squamous cell carcinoma. METHODS: Electronic databases, such as PubMed, Embase
and Cochrane library, were searched to identify studies evaluating PD-L1
expression and overall survival (OS) in these patients. RevMan 5.3 software was
used for meta-analysis. RESULTS: A total of 12 studies that involved 1595
patients were included. Pooled hazard ratio (HR) 1.02 (95%CI= 0.93-1.11,P=0.71)
indicated that the association between PD-L1 expression and overall survival (OS)
was not significant. The pooled odds ratios (ORs) indicated that PD-L1 expression
was associated with gender (OR=0.64, 95%CI=0.48-0.85, P=0.002), differentiation
(OR=0.58, 95%CI=0.37-0.90, P=0.01) and HPV infection (OR=1.91, 95%CI=1.13-3.23,
P=0.02). However, PD-L1 had no correlation with tumour size, and lymph node
status. CONCLUSIONS: PD-L1 expression may not be an independent predictor of
prognosis of patients with OSCC. Well-designed large cohort studies are needed to
confirm these findings.
PMID- 29946654
TI - [Perioperative nursing of zygomatic implant surgery for patients with severe
periodontitis].
AB - PURPOSE: To analyze the perioperative nursing characteristics about severe
periodontitis patients with immediate zygomatic implantation, and to summarize
the clinical nursing experience. METHODS: Preoperatively, all patients received
psychological counseling, oral hygiene instruction, and periodontal care with
necessary means after physical examination. Cooperative procedures were preformed
between nurses and surgeon during operation. After operation, nursing
interventions were given including wound care, pain control, ice compression,
appropriate diet and close follow-up. RESULTS: All patients were successfully
operated without serious complications. Favorable implant primary stability was
achieved in each patient. No patient developed wound dehiscence, one patient had
wound pain and one patient had minor facial swelling. Temporary restoration was
conducted to restore occlusal relationship and masticatory function within 48
hours. CONCLUSIONS: Comprehensive nursing intervention during perioperative
period is necessary and deserves to be applied for patients with severe
periodontitis who are treated with immediate zygomatic implant surgery.
PMID- 29946655
TI - [Evaluation of modified scene simulation teaching of endodontics in pre -clinical
practice].
AB - PURPOSE: To evaluate the effect of modified scene simulation teaching of
endodontics in pre-clinical teaching. METHODS: Forty students were randomly
divided into the experimental group and control group, there were 20 students in
each group. Students in the experimental group were taught with modified scene
simulation teaching method, while students in the control group were taught with
traditional teaching method. The teaching quality was compared with SPSS 18.0
software package. RESULTS: The score of the experimental group was significantly
higher than the control group in history taking, medical records writing and
practical performance(P<0.05). CONCLUSIONS: The teaching effect of modified scene
simulation teaching in pre-clinical teaching is better than traditional teaching
method. It makes students better grasp the clinical medical essentials and feels
the patient's feelings, as well as help the students to improve their subjective
initiative of learning.
PMID- 29946657
TI - Brief Commentary: Laboratory Accuracy of Hemoglobin A1c Ranges and Treatment
Targets for Patients With Type 2 Diabetes.
PMID- 29946656
TI - Association of Gestational Age at Birth With Symptoms of Attention
Deficit/Hyperactivity Disorder in Children.
AB - Importance: Preterm birth is associated with an increased risk of attention
deficit/hyperactivity disorder (ADHD); however, it is unclear to what extent this
association can be explained by shared genetic and environmental risk factors and
whether gestational age at birth is similarly related to inattention and
hyperactivity/impulsivity and to the same extent in boys and girls. Objectives:
To investigate the association between gestational age at birth and symptoms of
ADHD in preschool and school-age children after adjusting for unmeasured genetic
and environmental risk factors. Design, Setting, and Participants: In this
prospective, population-based cohort study, pregnant women were recruited from
across Norway from January 1, 1999, through December 31, 2008. Results of a
conventional cohort design were compared with results from a sibling-comparison
design (adjusting for genetic and environmental factors shared within families)
using data from the Norwegian Mother and Child Cohort Study. Data analysis was
performed from October 1, 2017, through March 16, 2018. Exposures: Analyses
compared children and siblings discordant for gestational age group: early
preterm (delivery at gestational weeks 22-33), late preterm (delivery at
gestational weeks 34-36), early term (delivery at gestational weeks 37-38),
delivery at gestational week 39, reference group (delivery at gestational week
40), delivery at gestational week 41, and late term (delivery after gestational
week 41). Main Outcomes and Measures: Maternally reported symptoms of ADHD in
children at 5 years of age and symptoms of inattention and
hyperactivity/impulsivity at 8 years of age. Covariates included child and
pregnancy characteristics associated with the week of delivery and the outcomes.
Results: A total of 113 227 children (55 187 [48.7%] female; 31 708 [28.0%] born
at gestational week 40), including 33 081 siblings (16 014 female [48.4%]; 9705
[29.3%] born at gestational week 40), were included in the study. Children born
early preterm were rated with more symptoms of ADHD, inattention, and
hyperactivity/impulsivity than term-born children. After adjusting for unmeasured
genetic and environmental factors, children born early preterm had a mean score
that was 0.24 SD (95% CI, 0.14-0.34) higher on ADHD symptom tests, 0.33 SD (95%
CI, 0.24-0.42) higher on inattention tests, and 0.23 SD (95% CI, 0.14-0.32)
higher on hyperactivity/impulsivity tests compared with children born at
gestational week 40. Sex moderated the association of gestational age with
preschool ADHD symptoms, and the association appeared to be strongest among
girls. Early preterm girls scored a mean of 0.8 SD (95% CI, 0.12-1.46; P = .02)
higher compared with their term-born sisters. Conclusions and Relevance: After
accounting for unmeasured genetic and environmental factors, early preterm birth
was associated with a higher level of ADHD symptoms in preschool children. Early
premature birth was associated with inattentive but not hyperactive symptoms in 8
year-old children. This study demonstrates the importance of differentiating
between inattention and hyperactivity/impulsivity and stratifying on sex in the
study of childhood ADHD.
PMID- 29946658
TI - The Rule of the Artery Is Supreme. Or, Is It?
PMID- 29946659
TI - Progressive Infantile Scoliosis Managed With Osteopathic Manipulative Treatment.
PMID- 29946660
TI - Response.
PMID- 29946662
TI - Proposed Amendments to the AOA Constitution, Bylaws, and Code of Ethics.
PMID- 29946661
TI - Official Call: 2018 Annual Business Meeting of the American Osteopathic
Association.
PMID- 29946663
TI - Lymphatic Pump Treatment Mobilizes Bioactive Lymph That Suppresses Macrophage
Activity In Vitro.
AB - Context: By promoting the recirculation of tissue fluid, the lymphatic system
preserves tissue health, aids in the absorption of gastrointestinal lipids, and
supports immune surveillance. Failure of the lymphatic system has been implicated
in the pathogenesis of several infectious and inflammatory diseases. Thus,
interventions that enhance lymphatic circulation, such as osteopathic lymphatic
pump treatment (LPT), should aid in the management of these diseases. Objective:
To determine whether thoracic duct lymph (TDL) mobilized during LPT would alter
the function of macrophages in vitro. Methods: The thoracic ducts of 6 mongrel
dogs were cannulated, and TDL samples were collected before (baseline), during,
and 10 minutes after LPT. Thoracic duct lymph flow was measured, and TDL samples
were analyzed for protein concentration. To measure the effect of TDL on
macrophage activity, RAW 264.7 macrophages were cultured for 1 hour to acclimate.
After 1 hour, cell-free TDL collected at baseline, during LPT, and after TDL was
added at 5% total volume per well and co-cultured with or without 500 ng per well
of lipopolysaccharide (LPS) for 24 hours. As a control for the addition of 5%
TDL, macrophages were cultured with phosphate-buffered saline (PBS) at 5% total
volume per well and co-cultured with or without 500 ng per well of LPS for 24
hours. After culture, cell-free supernatants were assayed for nitrite (NO2-),
tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10). Macrophage
viability was measured using flow cytometry. Results: Lymphatic pump treatment
significantly increased TDL flow and the flux of protein in TDL (P<.001). After
culture, macrophage viability was approximately 90%. During activation with LPS,
baseline TDL, TDL during LPT, and TDL after LPT significantly decreased the
production of NO2-, TNF-alpha, and IL-10 by macrophages (P<.05). However, no
significant differences were found in viability or the production of NO2-, TNF
alpha, or IL-10 between macrophages cultured with LPS plus TDL taken before,
during, and after LPT (P>.05). Conclusion: The redistribution of protective lymph
during LPT may provide scientific rationale for the clinical use of LPT to reduce
inflammation and manage edema.
PMID- 29946664
TI - Oral Health Training in Osteopathic Medical Schools: Results of a National
Survey.
AB - Context: Oral health is a critical aspect of overall health, yet many vulnerable
communities struggle to access regular dental care and instead seek urgent
treatment from physicians. In addition to addressing the consequences of
untreated dental disease, physicians are in an ideal position to provide
preventive and referral dental services to patients. Osteopathic physicians make
up a substantial portion of the physician workforce and can play a central role
in increasing oral health care provision in medical settings. Objective: To
assess the extent of oral health curricula in osteopathic medical schools in the
United States, including content taught, evaluation practices, and influences and
barriers to providing oral health training perceived by educators at these
institutions. Methods: An invitation to participate in the survey was sent
electronically to deans of education at all osteopathic medical schools in the
United States. Four email reminders followed the initial invitation. In addition
to descriptive statistics, the associations between the number of curriculum
hours, affiliation with a dental school, and curricular content were evaluated.
Results: Of the 42 institutions contacted, 22 responded (response rate, 52%). The
majority of respondents (20 of 22 [91%]) reported the presence of some oral
health education at their institutions. Eighteen of 20 respondents (90%) reported
that their institution offered at least 1 hour of oral health curriculum over the
course of students' education. Greater numbers of curriculum hours were not
significantly associated with dental school affiliation or a formalized
relationship with oral health educators. Institutions affiliated with dental
schools were significantly more likely to include oral health in
interprofessional education exercises (P=.023) but were not significantly more
likely to cover any specific oral health topics. Seven of 17 respondents (41%)
were satisfied with the level of oral health competence their graduates
possessed. Conclusion: Oral health education is present at many osteopathic
medical schools, but the content covered and the extent of training varies
considerably.
PMID- 29946665
TI - Perplexing Rash: Challenges to Diagnosis and Management of Mycosis Fungoides.
AB - Mycosis fungoides is the most ubiquitous form of cutaneous T-cell lymphoma.
Diagnosis is arduous, as early phases often resemble common inflammatory
dermatoses. The principal histologic features of MF include medium to large-sized
cerebriform mononuclear cells in single or small clusters in the epidermis.
Treatment modalities are prodigious and relapses are common. The authors present
a case of a 69-year-old man with mycosis fungoides, followed by a review of
diagnostic modalities and phototherapeutic interventions for patients with this
condition. According to literature reports, monochromatic excimer light therapy
is the most advantageous and well-tolerated phototherapy modality for patients
with early patch stage mycosis fungoides.
PMID- 29946666
TI - Laparoscopic Adjustable Gastric Band Erosion Into the Stomach and Colon.
AB - Morbid obesity has reached epidemic proportions in the United States and
constitutes a significant cause of morbidity and mortality. Bariatric surgery
represents a viable and effective means of weight loss. Laparoscopic adjustable
gastric band placement is the most commonly used and least invasive bariatric
surgical technique. Although the complication rate is low, various complications
have been described, including erosion of the gastric band into the stomach. The
authors present a case of laparoscopic adjustable gastric band erosion, where
both the band and the tubing eroded into the stomach and colon, and the tubing
further eroded out of and back into the colon several times.
PMID- 29946667
TI - Safety of Chiropractic Manipulation in Patients With Migraines.
PMID- 29946668
TI - Effect of HVLA on Chronic Neck Pain and Dysfunction.
PMID- 29946669
TI - Effects of Adding Cervicothoracic Treatments to Shoulder Mobilization in
Subacromial Impingement Syndrome.
PMID- 29946670
TI - Manipulation Under Anesthesia Thaws Frozen Shoulder.
PMID- 29946671
TI - Treating Patients With Low Back Pain: Evidence vs Practice.
PMID- 29946672
TI - Reducing Low Back and Posterior Pelvic Pain During and After Pregnancy Using OMT.
PMID- 29946673
TI - Neuromuscular Manipulation Improves Pain Intensity and Duration in Primary
Dysmenorrhea.
PMID- 29946674
TI - Reducing Cesarean Delivery Rates and Length of Labor by Addressing Pelvic Shape.
PMID- 29946676
TI - Minocycline-Induced Hyperpigmentation.
PMID- 29946677
TI - Massively Enlarged Leiomyomatous Uterus.
PMID- 29946675
TI - Remote MFR Increases Hamstring Flexibility: Support for the Fascial Train Theory.
PMID- 29946678
TI - Osteopathic Lymphatic Pump Techniques.
PMID- 29946679
TI - Hospital-at-Home Care Programs-Is the Hospital of the Future at Home?
PMID- 29946681
TI - How to Prepare for Your Child's Health Supervision Visit.
PMID- 29946680
TI - Trends in Weight Loss Efforts Among US Adolescents With Overweight and Obesity.
PMID- 29946683
TI - Depression and Suicidal Ideation Among HIV-Infected Adults Receiving Efavirenz
Versus Nevirapine in Uganda: A Prospective Cohort Study.
AB - Background: Evidence regarding potential adverse neuropsychiatric effects of
efavirenz is conflicting, and data from sub-Saharan Africa, where 70% of persons
living with HIV (PLHIV) reside and efavirenz is used as first-line therapy, are
limited. Objective: To estimate associations between efavirenz use and depression
and suicidal ideation among PLHIV in Uganda. Design: Prospective observational
cohort study. (ClinicalTrials.gov: NCT01596322). Setting: Mbarara, Uganda.
Participants: Adult PLHIV enrolled at the start of antiretroviral therapy (ART)
and observed every 3 to 4 months from 2005 to 2015. Measurements: The exposure of
interest was time-varying efavirenz use, defined as use during the 7 days and in
60 or more of the 90 days before a study visit, compared with nevirapine use.
Self-reported outcomes were depression, defined as a mean score greater than 1.75
on the Hopkins Symptom Checklist depression subscale, and suicidal ideation.
Multivariable-adjusted generalized estimating equations (GEE) logistic
regression, Cox proportional hazards regression, and marginal structural models
were fit to estimate the association between efavirenz use and the risk for
depression and suicidal ideation. Results: 694 participants (median age, 33
years; median pretreatment CD4+ count, 1.8 * 109 cells/L) contributed 1200 person
years of observation (460 person-years receiving efavirenz). No baseline
differences in depression or suicidal ideation were found between patients ever
exposed to efavirenz and those never exposed to efavirenz and receiving
nevirapine (P > 0.80 for both). Of 305 participants ever-exposed to efavirenz, 61
(20.0%) and 19 (6.2%) had depression and suicidal ideation, respectively, on at
least 1 follow-up visit, compared with 125 (32.1%) and 47 (12.1%) of the 389 who
received nevirapine. In adjusted GEE models, efavirenz use was associated with
decreased odds of depression compared with nevirapine use (adjusted odds ratio,
0.62 [95% CI, 0.40 to 0.96]) and was not significantly associated with suicidal
ideation (adjusted odds ratio, 0.61 [CI, 0.30 to 1.25]). Time-to-event and
marginal structural models yielded similar estimates. Limitation: Nonrandom
assignment to treatment and substantial differences between the efavirenz and
nevirapine groups. Conclusion: No evidence was found that use of efavirenz in
first-line ART increased the risk for depression or suicidal ideation compared
with nevirapine use among PLHIV in Uganda. Primary Funding Source: National
Institutes of Health.
PMID- 29946682
TI - Site of Death, Place of Care, and Health Care Transitions Among US Medicare
Beneficiaries, 2000-2015.
AB - Importance: End-of-life care costs are high and decedents often experience poor
quality of care. Numerous factors influence changes in site of death, health care
transitions, and burdensome patterns of care. Objective: To describe changes in
site of death and patterns of care among Medicare decedents. Design, Setting, and
Participants: Retrospective cohort study among a 20% random sample of 1 361 870
decedents who had Medicare fee-for-service (2000, 2005, 2009, 2011, and 2015) and
a 100% sample of 871 845 decedents who had Medicare Advantage (2011 and 2015) and
received care at an acute care hospital, at home or in the community, at a
hospice inpatient care unit, or at a nursing home. Exposures: Secular changes
between 2000 and 2015. Main Outcomes and Measures: Medicare administrative data
were used to determine site of death, place of care, health care transitions,
which are changes in location of care, and burdensome patterns of care.
Burdensome patterns of care were based on health care transitions during the last
3 days of life and multiple hospitalizations for infections or dehydration during
the last 120 days of life. Results: The site of death and patterns of care were
studied among 1 361 870 decedents who had Medicare fee-for-service (mean [SD]
age, 82.8 [8.4] years; 58.7% female) and 871 845 decedents who had Medicare
Advantage (mean [SD] age, 82.1 [8.5] years; 54.0% female). Among Medicare fee-for
service decedents, the proportion of deaths that occurred in an acute care
hospital decreased from 32.6% (95% CI, 32.4%-32.8%) in 2000 to 19.8% (95% CI,
19.6%-20.0%) in 2015, and deaths in a home or community setting that included
assisted living facilities increased from 30.7% (95% CI, 30.6%-30.9%) in 2000 to
40.1% (95% CI, 39.9%-30.3% ) in 2015. Use of the intensive care unit during the
last 30 days of life among Medicare fee-for-service decedents increased from
24.3% (95% CI, 24.1%-24.4%) in 2000 and then stabilized between 2009 and 2015 at
29.0% (95% CI, 28.8%-29.2%). Among Medicare fee-for-service decedents, health
care transitions during the last 3 days of life increased from 10.3% (95% CI,
10.1%-10.4%) in 2000 to a high of 14.2% (95% CI, 14.0%-14.3%) in 2009 and then
decreased to 10.8% (95% CI, 10.6%-10.9%) in 2015. The number of decedents
enrolled in Medicare Advantage during the last 90 days of life increased from 358
600 in 2011 to 513 245 in 2015. Among decedents with Medicare Advantage, similar
patterns in the rates for site of death, place of care, and health care
transitions were observed. Conclusions and Relevance: Among Medicare fee-for
service beneficiaries who died in 2015 compared with 2000, there was a lower
likelihood of dying in an acute care hospital, an increase and then stabilization
of intensive care unit use during the last month of life, and an increase and
then decline in health care transitions during the last 3 days of life.
PMID- 29946684
TI - Osteoporosis Screening-2 Steps May Be Too Much for Women Younger Than 65 Years.
PMID- 29946686
TI - Does Contralateral Inhibition of Transient Evoked Otoacoustic Emissions Suggest
Sex or Ear Laterality Effects?
AB - Purpose: The purpose of this study was to examine contralateral inhibition of
transient evoked otoacoustic emissions (TEOAEs) in young adults with normal
hearing as a function of ear and sex. Method: Young female (n = 50) and male (n =
50) adults with normal hearing participated. TEOAEs were measured bilaterally
with 80 dB peSPL nonlinear clicks and 60 dB peSPL linear clicks with and without
a contralateral broadband noise elicitor at 65 dB SPL. Absolute TEOAE inhibition
and normalized TEOAE inhibition (i.e., percentage of inhibition) were examined.
Results: With both 80 and 60 dB peSPL evoking stimuli, there were significant
main effects of ear and sex (p < .05). TEOAE levels were larger in women and in
the right ear. There were no statistically significant main effects of ear and
sex on absolute TEOAE inhibition (p > .05). Significant main effects of ear and
sex were, however, found with normalized TEOAE inhibition (p < .05; greater in
men and in the left ear). Statistically significant negative correlations and
significant linear predictive relations were found between TEOAE levels and
normalized TEOAE inhibitions in both ears (p < .001). There is no evidence of the
same with absolute inhibition of TEOAEs (p > .05). Conclusions: If one considers
that efferent inhibition of TEOAEs is an absolute quantity, the significant
effect of ear and sex on normalized inhibition and the negative association and
linear predictive relationship between TEOAE level and inhibition can be viewed
as spurious effects. As such, contralateral inhibition of TEOAEs does not suggest
sex or ear laterality effects.
PMID- 29946685
TI - Association of Retinal Nerve Fiber Layer Thinning With Current and Future
Cognitive Decline: A Study Using Optical Coherence Tomography.
AB - Importance: Identifing potential screening tests for future cognitive decline is
a priority for developing treatments for and the prevention of dementia.
Objective: To examine the potential of retinal nerve fiber layer (RNFL) thickness
measurement in identifying those at greater risk of cognitive decline in a large
community cohort of healthy people. Design, Setting, and Participants: UK Biobank
is a prospective, multicenter, community-based study of UK residents aged 40 to
69 years at enrollment who underwent baseline retinal optical coherence
tomography imaging, a physical examination, and a questionnaire. The pilot study
phase was conducted from March 2006 to June 2006, and the main cohort underwent
examination for baseline measures from April 2007 to October 2010. Four basic
cognitive tests were performed at baseline, which were then repeated in a subset
of participants approximately 3 years later. We analyzed eyes with high-quality
optical coherence tomography images, excluding those with eye disease or vision
loss, a history of ocular or neurological disease, or diabetes. We explored
associations between RNFL thickness and cognitive function using multivariable
logistic regression modeling to control for demographic as well as physiologic
and ocular variation. Main Outcomes and Measures: Odds ratios (ORs) for cognitive
performance in the lowest fifth percentile in at least 2 of 4 cognitive tests at
baseline, or worsening results on at least 1 cognitive test at follow-up. These
analyses were adjusted for age, sex, race/ethnicity, height, refraction,
intraocular pressure, education, and socioeconomic status. Results: A total of 32
038 people were included at baseline testing, for whom the mean age was 56.0
years and of whom 17 172 (53.6%) were women. A thinner RNFL was associated with
worse cognitive performance on baseline assessment. A multivariable regression
controlling for potential confounders showed that those in the thinnest quintile
of RNFL were 11% more likely to fail at least 1 cognitive test (95% CI, 2.0%
2.1%; P = .01). Follow-up cognitive tests were performed for 1251 participants
(3.9%). Participants with an RNFL thickness in the 2 thinnest quintiles were
almost twice as likely to have at least 1 test score be worse at follow-up
cognitive testing (quintile 1: OR, 1.92; 95% CI, 1.29-2.85; P < .001; quintile 2:
OR, 2.08; 95% CI, 1.40-3.08; P < .001). Conclusions and Relevance: A thinner RNFL
is associated with worse cognitive function in individuals without a
neurodegenerative disease as well as greater likelihood of future cognitive
decline. This preclinical observation has implications for future research,
prevention, and treatment of dementia.
PMID- 29946687
TI - Newborn Screening and Emerging Therapies for X-Linked Adrenoleukodystrophy.
PMID- 29946688
TI - Teleaudiology Services for Rehabilitation With Hearing Aids in Adults: A
Systematic Review.
AB - Purpose: This review examined (a) the current evidence from studies on
teleaudiology applications for rehabilitation of adults with hearing impairment
with hearing aids and (b) whether it is sufficient to support the translation
into routine clinical practice. Method: A search strategy and eligibility
criteria were utilized to include articles specifically related to hearing aid
fitting and follow-up procedures that are involved in consultations for the
rehabilitation of adults, where the service was provided by the clinician by
teleaudiology. A search using key words and Medical Subject Headings (MeSH) was
conducted on the main electronic databases that index health-related studies. The
included studies were assessed using validated evaluation tools for
methodological quality, level of evidence, and grade recommendations for
application into practice. Results: Fourteen studies were identified as being
within the scope of this review. The evaluation tools showed that none of these
studies demonstrated either a strong methodological quality or high level of
evidence. Analysis of evidence identified 19 activities, which were classified
into service outcomes categories of feasibility, barriers, efficiency, quality,
and effectiveness. Recommendations could be made regarding the (a) feasibility,
(b) barriers, and (c) efficiency of teleaudiology for the rehabilitation of
hearing loss with hearing aids. Conclusion: This review provides up-to-date
evidence for teleaudiology hearing aid services in new and experienced hearing
aid users in different practice settings. Findings direct future research
priorities to strengthen evidence-based practice. There is a need for further
studies of many aspects of teleaudiology services for rehabilitation with hearing
aids to support their implementation into clinical practice. Supplemental
Material: https://doi.org/10.23641/asha.6534473.
PMID- 29946689
TI - Electrocardiographic Findings in a Woman With Dextrocardia and Cyanosis.
PMID- 29946690
TI - ESPACOMP Medication Adherence Reporting Guideline (EMERGE).
AB - Research on assessing or managing medication adherence applies approaches from
observational, interventional, and implementation science that spans many
disciplines and demands coherent conceptualization, valid methods, appropriate
analyses, and complete and accurate reporting. To ensure such reporting, the
European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP)
Medication Adherence Reporting Guideline (EMERGE) recommends standard reporting
approaches based on an accepted taxonomy. This guideline is derived from a
literature review, a reactive Delphi study with 26 medication adherence experts
from many countries and disciplines, and feedback from ESPACOMP members. It is
designed to supplement existing guidelines for health research reporting and is
structured around 4 minimum reporting criteria and 17 items reflecting best
reporting practice. By enhancing and harmonizing research reporting, EMERGE aims
to advance research and, ultimately, patient outcomes.
PMID- 29946691
TI - Subacute Progressive Ptosis, Ophthalmoplegia, Gait Instability, and Cognitive
Changes.
PMID- 29946692
TI - Brief Commentary: Social Determinants of Health and Treatment Targets for Type 2
Diabetes.
PMID- 29946693
TI - Association of a Bundled Hospital-at-Home and 30-Day Postacute Transitional Care
Program With Clinical Outcomes and Patient Experiences.
AB - Importance: Hospital-at-home (HaH) care provides acute hospital-level care in a
patient's home as a substitute for traditional inpatient care. In September 2017,
the Physician-Focused Payment Model Technical Advisory Committee recommended
implementation of an alternative payment model for a new model of HaH that
bundles the acute episode with 30 days of postacute transitional care. Objective:
To report outcomes of this new payment model for HaH care. Design, Setting, and
Participants: Case-control study of HaH care patients with a concurrent control
group of hospital inpatients recruited from emergency departments (EDs) and
residences in New York City from November 18, 2014, to August 31, 2017. HaH
patients were 18 years or older with fee-for-service Medicare and acute medical
illness requiring inpatient-level care. Control patients met HaH eligibility but
refused participation or were seen in the ED when a HaH admission could not be
initiated. Exposures: HaH care or inpatient care. Main Outcomes and Measures:
Primary outcomes were acute period length of stay (LOS), all-cause 30-day
hospital readmissions and ED visits, admissions to skilled nursing facilities
(SNFs), referral to a certified home health care agency, and patient experiences
with care. Analyses accounted for nonrandom selection using inverse probability
weighting. Results: Among the 507 patients enrolled (mean [SD] age, 74.6 [15.7]
years; 68.6% women), data were available on all patients 30 days postdischarge.
HaH patients (n = 295) were older than controls (n = 212) and more likely to have
a preacute functional impairment. HaH patients had shorter LOS (3.2 days vs 5.5
days; difference, -2.3 days; 95% CI, -1.8 to -2.7 days; weighted P < .001); lower
rates of readmissions (8.6% [25] vs 15.6% [32]; difference, -7.0%; 95% CI, -12.9%
to -1.1%; weighted P < .001), ED revisits (5.8% [17] vs 11.7% [24]; difference,
5.9%; 95% CI, -11.0% to -0.7%; weighted P < .001), and SNF admissions (1.7% [5]
vs 10.4% [22]; difference, -8.7%; 95% CI, -13.0% to -4.3%; weighted P < .001);
and were also more likely to rate their hospital care highly (68.8% [119] vs
45.3% [67]; difference, 23.5%; 95% CI, 12.9% to 34.1%; weighted P < .001). There
were no differences in referrals to certified home health agencies. Conclusions
and Relevance: HaH care bundled with a 30-day postacute transitional care episode
was associated with better patient outcomes and ratings of care compared with
inpatient hospitalization. This model warrants consideration for addition to
Medicare's current portfolio of shared savings programs.
PMID- 29946694
TI - Participation in a Voluntary Bundled Payment Program by Organizations Providing
Care After an Acute Hospitalization.
PMID- 29946696
TI - Error in Results Section of the Abstract.
PMID- 29946695
TI - Exploring Optimal Stimulus Frequency Ratio for Measurement of the Quadratic f2-f1
Distortion Product Otoacoustic Emission in Humans.
AB - Purpose: Distortion product otoacoustic emissions (DPOAEs) are a by-product of
active cochlear processes that lead to the compressive nonlinearity of healthy
ears. The most commonly studied emission is at the frequency 2f1-f2, but there
has been recent interest in using the quadratic distortion product at the
frequency f2-f1 to detect cochleopathies including endolymphatic hydrops. Before
the DPOAE at f2-f1 can be applied clinically in any capacity, optimal stimulus
parameters for its elicitation must be established. Method: We investigated
stimulus parameters for the DPOAEs at f2-f1 and 2f1-f2 in 23 adults with normal
hearing. Logarithmically swept tones between approximately 0.6 and 20 kHz (L1 =
L2 = 70 dB SPL) served as the higher frequency stimulus (f2). DPOAEs were
measured for 6 f2/f1 ratios: 1.14, 1.18, 1.22, 1.30, 1.32, and 1.36. Results:
Both DPOAEs were consistently measurable. In line with previous investigations,
the highest levels of the DPOAE at 2f1-f2 were generated between f2/f1 ratios of
1.14-1.22, with a peak in the level ratio function at 1.22. In contrast, f2-f1
was less influenced by ratio, although the narrowest ratio (1.14) produced
slightly higher levels across frequency. Conclusion: The DPOAE at f2-f1 is
measurable in individuals with normal hearing up to f2 of 20 kHz at narrow f2/f1
ratios. Measurements at additional stimulus levels and in subjects with hearing
impairment will be needed before clinical implementation.
PMID- 29946697
TI - The Roles of Retrieval Practice Versus Errorless Learning in Strengthening
Lexical Access in Aphasia.
AB - Purpose: The purpose of this study was to determine how 2 methods known to
improve naming impairment in aphasia (i.e., retrieval practice and errorless
learning) affect lexical access. We hypothesized that instances of naming during
retrieval practice use and strengthen item-specific connections in each of 2
stages of lexical access: Stage 1, meaning-to-word connections, and Stage 2, word
to-phonology connections. In contrast, errorless learning prioritizes
opportunities for repeating words, which we expect to primarily strengthen item
specific connections in Stage 2 because repetition circumvents the need for
semantically driven word retrieval. Method: We tested the outcomes of retrieval
practice versus errorless learning training for items that were selected because
the naming errors they elicited suggested weakened connections at Stage 1 or at
Stage 2 of lexical access for each of 10 individuals with chronic aphasia. Each
participant's Stage 1 items and Stage 2 items were divided evenly between the 2
training conditions. Naming tests were administered 1 day and 1 week after
training to assess retention of training gains. We also examined whether the
participants' pretraining naming error profiles were associated with the relative
efficacy of retrieval practice versus errorless learning. Results: The
posttraining naming tests showed an advantage of retrieval practice over
errorless learning for Stage 1 items and an advantage of errorless learning over
retrieval practice for Stage 2 items. In addition, greater percentages of
phonological error naming responses prior to training were associated with
greater posttraining accuracy in the errorless learning condition relative to the
retrieval practice condition. Conclusions: The findings suggest that the
advantage of retrieval practice for naming impairment in aphasia largely results
from greater strengthening of practiced semantic-lexical connections compared
with errorless learning, which prioritizes repetition and, therefore, mainly
confers strengthening of practiced lexical-phonological connections.
Understanding how specific training conditions improve naming can help predict
the relative efficacy of each method for individuals with aphasia.
PMID- 29946698
TI - Brief Commentary: The Glycemic Target Guideline Controversy: Same Evidence,
Different Perspectives, and a Proposal for Common Ground.
PMID- 29946700
TI - Brief Commentary: Glycemic Targets for Older Adults With Type 2 Diabetes.
PMID- 29946699
TI - Reframing Optimal Outcomes in Autism.
PMID- 29946701
TI - Assessment of Subjective Visual Vertical (SVV) Using the "Bucket Test" and the
Virtual SVV System.
AB - Objective: The purpose of this study was to describe the variability and test
retest reliability of a commercially available subjective visual vertical (SVV)
system known as Virtual SVV (Interacoustics). In addition, the study aimed to
compare the reliability of the Virtual system with a previously established
bucket test of SVV. Study Design: Fifteen participants with normal hearing,
normal middle ear function, and normal utricular function were included in the
study. Each participant underwent static SVV testing using both the Virtual
system and the bucket test. Subjects completed 2 testing sessions to determine
test-retest reliability. For each test, data were collected with the head at 0
degrees , tilted 45 degrees to the right, and tilted 45 degrees to the left.
Setting: This study was conducted in a balance function laboratory embedded in a
large, tertiary care otology clinic. Results: The mean SVV values obtained with
the Virtual system were within 1 degrees -2 degrees from 0 with the head
positioned at 0 degrees , which is in agreement with many other studies of SVV
with the head at 0 degrees (Akin & Murnane, 2009; Halmagyi & Curthoys, 1999;
Zwergal, Rettinger, Frenzel, Dieterich, & Strupp, 2009). Using the intraclass
correlation coefficient, test-retest reliability of the Virtual system was
excellent in the 45 degrees left position and fair to good in the 45 degrees
right and 0 degrees position. Test-retest reliability of the bucket test was
poor in all head positions. Conclusions: The Virtual system is a more reliable
measure of static SVV than the bucket test. Therefore, the Virtual system could
be utilized as a screening device for utricular dysfunction in busy clinical
settings.
PMID- 29946703
TI - Percutaneous Ablation Versus Partial and Radical Nephrectomy for T1a Renal
Cancer: A Population-Based Analysis.
AB - Background: Stage T1a renal cell carcinoma (RCC) (tumors <4 cm) is usually
curable. Nephron-sparing partial nephrectomy (PN) has replaced radical
nephrectomy (RN) as the standard of care for these tumors. Radical nephrectomy
remains the first alternative treatment option, whereas percutaneous ablation
(PA), a newer, nonsurgical treatment, is recommended less strongly because of the
relative paucity of comparative PA data. Objective: To compare PA, PN, and RN
outcomes. Design: Observational cohort analysis using inverse probability of
treatment-weighted propensity scores. Setting: Population-based SEER
(Surveillance, Epidemiology, and End Results) cancer registry data linked to
Medicare claims. Patients: Persons aged 66 years or older who received treatment
for T1a RCC between 2006 and 2011. Interventions: PA versus PN and RN.
Measurements: RCC-specific and overall survival, 30- and 365-day postintervention
complications. Results: 4310 patients were followed for a median of 52 months for
overall survival and 42 months for RCC-specific survival. After PA versus PN, the
5-year RCC-specific survival rate was 95% (95% CI, 93% to 98%) versus 98% (CI,
96% to 99%); after PA versus RN, 96% (CI, 94% to 98%) versus 95% (CI, 93% to
96%). After PA versus PN, the 5-year overall survival rate was 77% (CI, 74% to
81%) versus 86% (CI, 84% to 88%); after PA versus RN, 74% (CI, 71% to 78%) versus
75% (CI, 73% to 77%). Cumulative rates of renal insufficiency 31 to 365 days
after PA, PN, and RN were 11% (CI, 8% to 14%), 9% (CI, 8% to 10%), and 18% (CI,
17% to 20%), respectively. Rates of nonurologic complications within 30 days
after PA, PN, and RN were 6% (CI, 4% to 9%), 29% (CI, 27% to 30%), and 30% (CI,
28% to 32%), respectively. Ten percent of patients in the PN group had
intraoperative conversion to RN. Seven percent of patients in the PA group
received additional PA within 1 year of treatment. Limitations: Analysis of
observational data may have been affected by residual confounding by provider or
from selection bias toward younger, healthier patients in the PN group. Findings
from this older study population are probably less applicable to younger
patients. Use of SEER-Medicare linked files prevented analysis of patients who
received treatment after 2011, possibly reducing generalizability to the newest
PA, PN, and RN techniques. Conclusion: For well-selected older adults with T1a
RCC, PA may result in oncologic outcomes similar to those of RN, but with less
long-term renal insufficiency and markedly fewer periprocedural complications.
Compared with PN, PA may be associated with slightly shorter RCC-specific
survival but fewer periprocedural complications. Primary Funding Source:
Association of University Radiologists GE Radiology Research Academic Fellowship
and Society of Interventional Radiology Foundation.
PMID- 29946702
TI - Association of Retinal Neurodegeneration on Optical Coherence Tomography With
Dementia: A Population-Based Study.
AB - Importance: Retinal structures may serve as a biomarker for dementia, but
longitudinal studies examining this link are lacking. Objective: To investigate
the association of inner retinal layer thickness with prevalent and incident
dementia in a general population of Dutch adults. Design, Setting, and
Participants: From September 2007 to June 2012, participants from the prospective
population-based Rotterdam Study who were 45 years and older and had gradable
retinal optical coherence tomography images and at baseline were free from
stroke, Parkinson disease, multiple sclerosis, glaucoma, macular degeneration,
retinopathy, myopia, hyperopia, and optic disc pathology were included. They were
followed up until January 1, 2015, for the onset of dementia. Exposures: Inner
retinal layer thicknesses (ie, retinal nerve fiber layer [RNFL]) and ganglion
cell-inner plexiform layer (GC-IPL) thicknesses measured on optical coherence
tomography images. Main Outcomes and Measures: Odds ratios and hazard ratios for
incident dementia per SD decrease in retinal layer thickness adjusted for age,
sex, education, and cardiovascular risk factors. Results: Of 5065 individuals
eligible for optical coherence tomography scanning, 3289 (64.9%) (mean [SD] age
68.9 [9.9] years, 1879 [57%] women) were included in the analysis. Of these 3289
individuals, 41 (1.2%) already had dementia. Thinner GC-IPL was associated with
prevalent dementia (odds ratio per SD decrease in GC-IPL, 1.37 [95% CI, 0.99
1.90]). No association was found of RNFL with prevalent dementia. During 14 674
person-years of follow-up (mean [SD], 4.5 [1.6] years), 86 individuals (2.6%)
developed dementia of whom 68 (2.1%) had Alzheimer disease. Thinner RNFL at
baseline was associated with an increased risk of developing dementia (hazard
ratio per SD decrease in RNFL, 1.44 [95% CI, 1.19-1.75]), which was similar for
Alzheimer disease (hazard ratio, 1.43 [95% CI, 1.15-1.78]). No association was
found between GC-IPL thickness and incident dementia (hazard ratio, 1.13 [95% CI,
0.90-1.43]). Conclusions and Relevance: Thinner RNFL is associated with an
increased risk of dementia, including Alzheimer disease, suggesting that retinal
neurodegeneration may serve as a preclinical biomarker for dementia.
PMID- 29946704
TI - Brief Commentary: Confusing Treatment Guidelines for Patients With Type 2
Diabetes.
PMID- 29946705
TI - Defining, Estimating, and Communicating Overdiagnosis in Cancer Screening.
AB - The toll of inadequate health care is well-substantiated, but recognition is
mounting that "too much" is also possible. Overdiagnosis represents one harm of
too much medicine, but the concept can be confusing: It is often conflated with
related harms (such as overtreatment, misclassification, false-positive results,
and overdetection) and is difficult to measure because it cannot be directly
observed. Because the U.S. Preventive Services Task Force (USPSTF) issues
screening recommendations aimed largely at healthy persons, it has a particular
interest in understanding harms related to screening, especially but not limited
to overdiagnosis. In support of the USPSTF, the authors summarize the knowledge
and provide guidance on defining, estimating, and communicating overdiagnosis in
cancer screening. To improve consistency, thinking, and reporting about
overdiagnosis, they suggest a specific definition. The authors articulate how
variation in estimates of overdiagnosis can arise, identify approaches to
estimating overdiagnosis, and describe best practices for communicating the
potential for harm due to overdiagnosis.
PMID- 29946707
TI - Screening for Osteoporosis.
PMID- 29946706
TI - A Woman With Fever and Lymphadenopathy.
PMID- 29946708
TI - Abortion-Related Adverse Events by Facility Type: Reassurance From a National
Analysis.
PMID- 29946709
TI - NIH-Sponsored Trial of Universal Influenza Vaccine.
PMID- 29946711
TI - Federal Rule Overrides State Telemedicine Restrictions.
PMID- 29946710
TI - Phone Apps for Patients With Diabetes.
PMID- 29946713
TI - Doctors in Congress.
PMID- 29946714
TI - Prevalence of Missed Opportunities for HIV Testing Among Persons Unaware of Their
Infection.
PMID- 29946715
TI - Price Setting for Physician Services.
PMID- 29946716
TI - Virtual Care as a Specialty.
PMID- 29946717
TI - Virtual Care as a Specialty.
PMID- 29946718
TI - Patent Foramen Ovale and Risk of Perioperative Stroke.
PMID- 29946719
TI - Price Setting for Physician Services-Reply.
PMID- 29946720
TI - Virtual Care as a Specialty-Reply.
PMID- 29946721
TI - Patent Foramen Ovale and Risk of Perioperative Stroke-Reply.
PMID- 29946722
TI - Bath Emollients Offer Little Added Benefit in Pediatric Eczema.
PMID- 29946723
TI - Phone App No Help in Controlling Hypertension.
PMID- 29946724
TI - MDMA-Assisted Psychotherapy for PTSD.
PMID- 29946725
TI - Abeta-Clearing Drug Fails to Slow Alzheimer Disease.
PMID- 29946726
TI - Neurocognitive Benefits from Breastfeeding May Not Endure.
PMID- 29946727
TI - Association of Facility Type With Procedural-Related Morbidities and Adverse
Events Among Patients Undergoing Induced Abortions.
AB - Importance: Multiple states have laws requiring abortion facilities to meet
ambulatory surgery center (ASC) standards. There is limited evidence regarding
abortion-related morbidities and adverse events following abortions performed at
ASCs vs office-based settings. Objective: To compare abortion-related morbidities
and adverse events at ASCs vs office-based settings. Design, Setting, and
Participants: Retrospective cohort study of women with US private health
insurance who underwent induced abortions in an ASC or office-based setting
(January 1, 2011-December 31, 2014). Outcomes were abstracted from a large
national private insurance claims database during the 6 weeks following the
abortion (date of final follow-up, February 11, 2015). Exposures: Facility type
for abortion (ASCs vs office-based settings, including facilities such as
abortion clinics, nonspecialized clinics, and physician offices). Main Outcomes
and Measures: The primary outcome was any abortion-related morbidity or adverse
event (such as retained products of conception, abortion-related infection,
hemorrhage, and uterine perforation) within 6 weeks after an abortion. Two
secondary outcomes, both subsets of the primary outcome, were major abortion
related morbidities and adverse events (such as hemorrhages treated with a
transfusion, missed ectopic pregnancies treated with surgery, and abortion
related infections that resulted in an overnight hospital admission) and abortion
related infections. Results: Among 49 287 women (mean age, 28 years [SD, 7.3])
who had 50 311 induced abortions, (23 891 [47%] first-trimester aspiration, 13
480 [27%] first-trimester medication, and 12 940 [26%] second trimester or
later), 5660 abortions (11%) were performed in ASCs and 44 651 (89%) in office
based settings. Overall, 3.33% had an abortion-related morbidity or adverse
event; 0.32% had a major abortion-related morbidity or adverse event; and 0.74%
had an abortion-related infection. In adjusted analyses, there was no
statistically significant difference between ASCs vs office-based settings,
respectively, in the rates of abortion-related morbidities or adverse events
(3.25% vs 3.33%, difference, -0.08%; [corrected] 95% CI, -0.58% to 0.43%;
adjusted OR, 0.97; 95% CI, 0.81-1.17), major morbidities or adverse events (0.26%
vs 0.33%; difference, -0.06%; 95% CI, -0.18% to 0.06%; adjusted OR, 0.78; 95% CI,
0.45-1.37), or infections (0.58% vs 0.77%; difference, -0.16%; 95% CI, -0.35% to
0.03%; adjusted OR, 0.75; 95% CI, 0.52-1.09). Conclusions and Relevance: Among
women with private health insurance who had an induced abortion, performance of
the abortion in an ambulatory surgical center compared with an office-based
setting was not associated with a significant difference in abortion-related
morbidities and adverse events. These findings, in addition to individual patient
and individual facility factors, may inform decisions about the type of facility
in which induced abortions are performed.
PMID- 29946729
TI - Annual Risk of Major Bleeding Among Persons Without Cardiovascular Disease Not
Receiving Antiplatelet Therapy.
AB - Importance: A decision to initiate aspirin therapy for primary prevention of
cardiovascular disease (CVD) requires consideration of both treatment benefits
and harms. The most significant harm associated with aspirin is major bleeding,
yet there is a paucity of data on bleeding risk in suitable community
populations. Objective: To determine the risk of major bleeding among people
without CVD who are not receiving antiplatelet therapy. Design, Setting, and
Participants: Prospective cohort study of 359 166 individuals aged 30 to 79 years
receiving primary care in New Zealand who had CVD risk assessment between 2002
and 2015. Participants were censored at the earliest date on which they had a
first major bleeding event, died, or met any baseline cohort exclusion criteria
or the study end date of December 31, 2015. Analyses were repeated after
excluding people with medical conditions associated with increased bleeding risk
(non-high-risk cohort; n=305 057) and after further excluding people receiving
other medications associated with increased bleeding risk (nonmedication cohort;
n=240 254). Exposures: Sex and age group in 10-year bands from 30 to 79 years.
Main Outcomes and Measures: Risk of a major bleeding event (hospitalization or
death associated with bleeding); nonfatal gastrointestinal tract bleeding; and
gastrointestinal tract bleeding-related case fatality. Results: Mean participant
age was 54 years (SD, 10 years), 44% were women, and 57% were European. Among the
359 166 individuals in the baseline cohort, 3976 had a major bleeding event
during 1 281 896 person-years of follow-up. Most had gastrointestinal (GI)
bleeding (n=2910 [73%]). There were 274 fatal bleeding events (7%), of which 153
were intracerebral. The risk of a nonfatal GI bleeding event per 1000 person
years was 2.19 (95% CI, 2.11-2.27), 1.77 (95% CI, 1.69-1.85) and 1.61 (95% CI,
1.52-1.69), in the baseline, non-high-risk, and nonmedication cohorts,
respectively. Case fatality associated with GI bleeding was 3.4% (95% CI, 2.2%
4.1%), 4.0% (95% CI, 3.2%-5.1%), and 4.6% (95% CI, 3.6%-6.0%) in the baseline,
non-high-risk, and nonmedication cohorts, respectively. Conclusions and
Relevance: In a population not receiving antiplatelet therapy, the annual risk of
major bleeding events and nonfatal major bleeding was estimated. These findings
could inform population-level guidelines for primary prevention of CVD.
PMID- 29946728
TI - Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously
Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial.
AB - Importance: Patients with metastatic colorectal cancer (CRC) have limited
effective and tolerable treatment options. Objective: To evaluate the efficacy
and safety of oral fruquintinib, a vascular endothelial growth factor receptor
(VEGFR) inhibitor, as third-line or later therapy in patients with metastatic
CRC. Design, Setting, and Participants: FRESCO (Fruquintinib Efficacy and Safety
in 3+ Line Colorectal Cancer Patients) was a randomized, double-blind, placebo
controlled, multicenter (28 hospitals in China), phase 3 clinical trial. From
December 2014 to May 2016, screening took place among 519 patients aged 18 to 75
years who had metastatic CRC that progressed after at least 2 lines of
chemotherapy but had not received VEGFR inhibitor therapy; 416 met the
eligibility criteria and were stratified by prior anti-VEGF therapy and K-ras
status. The final date of follow-up was January 17, 2017. Interventions: Patients
were randomized in a 2:1 ratio to receive either fruquintinib, 5 mg (n = 278) or
placebo (n = 138) orally, once daily for 21 days, followed by 7 days off in 28
day cycles, until disease progression, intolerable toxicity, or study withdrawal.
Main Outcomes and Measures: The primary end point was overall survival. Key
secondary efficacy endpoints were progression-free survival (time from
randomization to disease progression or death), objective response rate
(confirmed complete or partial response), and disease control rate (complete or
partial response, or stable disease recorded >=8 weeks postrandomization).
Duration of response was also assessed. Safety outcomes included treatment
emergent adverse events. Results: Of the 416 randomized patients (mean age, 54.6
years; 161 [38.7%] women), 404 (97.1%) completed the trial. Median overall
survival was significantly prolonged with fruquintinib compared with placebo (9.3
months [95% CI, 8.2-10.5] vs 6.6 months [95% CI, 5.9-8.1]); hazard ratio (HR) for
death, 0.65 (95% CI, 0.51-0.83; P < .001). Median progression-free survival was
also significantly increased with fruquintinib (3.7 months [95% CI, 3.7-4.6] vs
1.8 months [95% CI, 1.8-1.8] months); HR for progression or death, 0.26 (95% CI,
0.21 to 0.34; P < .001). Grades 3 and 4 treatment-emergent adverse events
occurred in 61.2% (170) of patients who received fruquintinib and 19.7% (27) who
received placebo. Serious adverse events were reported by 15.5% (43) of patients
in the fruquintinib group and 5.8% (8) in the placebo group, with 14.4% (40) of
fruquintinib-treated and 5.1% (7) of placebo-treated patients requiring
hospitalization. Conclusions and Relevance: Among Chinese patients with
metastatic CRC who had tumor progression following at least 2 prior chemotherapy
regimens, oral fruquintinib compared with placebo resulted in a statistically
significant increase in overall survival. Further research is needed to assess
efficacy outside of China. Trial Registration: ClinicalTrials.gov Identifier:
NCT02314819.
PMID- 29946730
TI - Screening for Osteoporosis to Prevent Fractures.
PMID- 29946732
TI - Making Room.
PMID- 29946734
TI - Screening to Prevent Osteoporotic Fractures: Updated Evidence Report and
Systematic Review for the US Preventive Services Task Force.
AB - Importance: Osteoporotic fractures cause significant morbidity and mortality.
Objective: To update the evidence on screening and treatment to prevent
osteoporotic fractures for the US Preventive Services Task Force. Data Sources:
PubMed, the Cochrane Library, EMBASE, and trial registries (November 1, 2009,
through October 1, 2016) and surveillance of the literature (through March 23,
2018); bibliographies from articles. Study Selection: Adults 40 years and older;
screening cohorts without prevalent low-trauma fractures or treatment cohorts
with increased fracture risk; studies assessing screening, bone measurement tests
or clinical risk assessments, pharmacologic treatment. Data Extraction and
Synthesis: Dual, independent review of titles/abstracts and full-text articles;
study quality rating; random-effects meta-analysis. Main Outcomes and Measures:
Incident fractures and related morbidity and mortality, diagnostic and predictive
accuracy, harms of screening or treatment. Results: One hundred sixty-eight fair-
or good-quality articles were included. One randomized clinical trial (RCT) (n =
12 483) comparing screening with no screening reported fewer hip fractures (2.6%
vs 3.5%; hazard ratio [HR], 0.72 [95% CI, 0.59-0.89]) but no other statistically
significant benefits or harms. The accuracy of bone measurement tests to identify
osteoporosis varied (area under the curve [AUC], 0.32-0.89). The pooled accuracy
of clinical risk assessments for identifying osteoporosis ranged from AUC of 0.65
to 0.76 in women and from 0.76 to 0.80 in men; the accuracy for predicting
fractures was similar. For women, bisphosphonates, parathyroid hormone,
raloxifene, and denosumab were associated with a lower risk of vertebral
fractures (9 trials [n = 23 690]; relative risks [RRs] from 0.32-0.64).
Bisphosphonates (8 RCTs [n = 16 438]; pooled RR, 0.84 [95% CI, 0.76-0.92]) and
denosumab (1 RCT [n = 7868]; RR, 0.80 [95% CI, 0.67-0.95]) were associated with a
lower risk of nonvertebral fractures. Denosumab reduced the risk of hip fracture
(1 RCT [n = 7868]; RR, 0.60 [95% CI, 0.37-0.97]), but bisphosphonates did not
have a statistically significant association (3 RCTs [n = 8988]; pooled RR, 0.70
[95% CI, 0.44-1.11]). Evidence was limited for men: zoledronic acid reduced the
risk of radiographic vertebral fractures (1 RCT [n = 1199]; RR, 0.33 [95% CI,
0.16-0.70]); no studies demonstrated reductions in clinical or hip fractures.
Bisphosphonates were not consistently associated with reported harms other than
deep vein thrombosis (raloxifene vs placebo; 3 RCTs [n = 5839]; RR, 2.14 [95% CI,
0.99-4.66]). Conclusions and Relevance: In women, screening to prevent
osteoporotic fractures may reduce hip fractures, and treatment reduced the risk
of vertebral and nonvertebral fractures; there was not consistent evidence of
treatment harms. The accuracy of bone measurement tests or clinical risk
assessments for identifying osteoporosis or predicting fractures varied from very
poor to good.
PMID- 29946736
TI - Insect Borne Disease Threat Grows.
PMID- 29946737
TI - Rise in Fall-Related Deaths.
PMID- 29946735
TI - Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task
Force Recommendation Statement.
AB - Importance: By 2020, approximately 12.3 million individuals in the United States
older than 50 years are expected to have osteoporosis. Osteoporotic fractures,
particularly hip fractures, are associated with limitations in ambulation,
chronic pain and disability, loss of independence, and decreased quality of life,
and 21% to 30% of patients who experience a hip fracture die within 1 year. The
prevalence of primary osteoporosis (ie, osteoporosis without underlying disease)
increases with age and differs by race/ethnicity. With the aging of the US
population, the potential preventable burden is likely to increase in future
years. Objective: To update the 2011 US Preventive Services Task Force (USPSTF)
recommendation on screening for osteoporosis. Evidence Review: The USPSTF
reviewed the evidence on screening for and treatment of osteoporotic fractures in
men and women, as well as risk assessment tools, screening intervals, and
efficacy of screening and treatment in subgroups. The screening population was
postmenopausal women and older men with no known previous osteoporotic fractures
and no known comorbid conditions or medication use associated with secondary
osteoporosis. Findings: The USPSTF found convincing evidence that bone
measurement tests are accurate for detecting osteoporosis and predicting
osteoporotic fractures in women and men. The USPSTF found adequate evidence that
clinical risk assessment tools are moderately accurate in identifying risk of
osteoporosis and osteoporotic fractures. The USPSTF found convincing evidence
that drug therapies reduce subsequent fracture rates in postmenopausal women. The
USPSTF found that the evidence is inadequate to assess the effectiveness of drug
therapies in reducing subsequent fracture rates in men without previous
fractures. Conclusions and Recommendation: The USPSTF recommends screening for
osteoporosis with bone measurement testing to prevent osteoporotic fractures in
women 65 years and older. (B recommendation) The USPSTF recommends screening for
osteoporosis with bone measurement testing to prevent osteoporotic fractures in
postmenopausal women younger than 65 years at increased risk of osteoporosis, as
determined by a formal clinical risk assessment tool. (B recommendation) The
USPSTF concludes that the current evidence is insufficient to assess the balance
of benefits and harms of screening for osteoporosis to prevent osteoporotic
fractures in men. (I statement).
PMID- 29946738
TI - Effects of newly developed compact robot-aided upper extremity training system
(Neuro-X(r)) in patients with stroke: A pilot study.
AB - OBJECTIVE: Robot-assisted rehabilitation therapy of the upper extremity after
stroke has been studied widely; however, robotic devices remain expensive and
bulky. The aim of this study was to evaluate the effects of a newly developed,
compact upper extremity training system (Neuro-X(r)) in patients with chronic
stroke. DESIGN: Pilot study. SUBJECTS: Fifteen patients with hemiplegia. METHODS:
Chronic patients with stroke underwent upper extremity training using a newly
developed upper extremity training system (Neuro-X(r); Apsun Inc., Seoul, Korea).
Patients were evaluated using the Fugl-Meyer Assessment (FMA), Hand Function Test
(HFT), Modified Ashworth Scale (MAS), and Korean Mini-Mental Status Evaluation (K
MMSE). The assessment started with "pre 1 evaluation" (A1), followed by repeated
"pre 2 evaluation" (A2) after 6 weeks without receiving any treatment, in order
to generate repeated baseline data. After the A2 evaluation, upper extremity
training was performed for 6 weeks. Post-training evaluation (B) was performed
after treatment. Obtained data (A1-A2-B) were compared. RESULTS: During the non
intervention phase (A1 to A2), no significant changes were found in the
aforementioned evaluations. However, in the intervention phase (A2 to B), results
of the FMA and HFT, and K-MMSE scores, except the MAS score, increased
significantly (p <0.05). CONCLUSION: The Neuro-X(r) training system improves
functioning of the upper extremity and cognition in patients with stroke after 6
weeks of training.
PMID- 29946739
TI - Steinernema poinari (Nematoda: Steinernematidae): a new symbiotic host of
entomopathogenic bacteria Xenorhabdus bovienii.
AB - Three strains of symbiotic bacteria were isolated from an entomopathogenic
nematode Steinernema poinari retrieved from soil in eastern Poland. Using 16S
rDNA, recA, gltX, gyrB, and dnaN gene sequences for phylogenetic analysis, these
strains were shown to belong to the species Xenorhabdus bovienii. The nucleotide
identity between the studied S. poinari microsymbionts and other X. bovienii
strains calculated for 16S rDNA and concatenated sequences of four protein-coding
genes was 98.7-100% and 97.9-99.5%, respectively. The phenotypic properties of
the isolates also supported their close phylogenetic relationship with X.
bovienii. All three tested X. bovienii strains of different Steinernema clade
origin supported the recovery of infective juveniles and subsequent development
of the nematode population. However, the colonization degree of new infective
juvenile generations was significantly affected by the bacterial host
donor/recipient. The colonization degree of infective juveniles reared on
bacterial symbionts deriving from a non-cognate clade of nematodes was extremely
low, but proved the possible host-switching between non-related Steinernema
species.
PMID- 29946740
TI - Patient-related quality of life after pelvic ring fractures in elderly.
AB - PURPOSE: Pelvic ring fractures, occurring in elderly patients are a challenging
problem. Little known is about the patient-related outcome after these injuries.
The primary objective of this study is to evaluate the quality of life after
pelvic ring injuries in patients aged over 60 years. METHODS: Patients (>= 60
years) with pelvic ring fractures treated in our trauma department between 2004
and 2014 were included. Next to patient data, injury-related details as well as
treatment details were assessed. After a follow-up of at least two years, the
survival rate and the patient-related outcome were evaluated using the SF-36 and
the EQ-5D score. RESULTS: One hundred ninety-six patients (138 women; 58 men;
mean age 75.3 +/- 7.8 years) were identified. Ninety-six patients were treated
operatively, 100 patients conservatively. The overall complication rate was
significantly lower for conservatively compared to operatively treated patients
(conservatively 18% vs. operatively 33%; p = 0.014). The total mortality rate
over 2 years is 29% with no significant difference of the two-year survival rate
(2-year survival rate: operatively 77% vs. non-operatively 65%; p = 0.126). Fifty
five patients completed the SF-36 and EQ-5D score after a mean follow-up of 4.2
+/- 2.9 years. The mean physical component score of the SF-36 is 33.6 +/- 8.3,
and the mean mental component score is 45.3 +/- 8.4. The mean EQ-5D VAS reached
62.5 +/- 27.9. CONCLUSION: Elderly patients with pelvic ring fractures show a
high mortality rate and a limited patient-related outcome. While the complication
rate of conservatively treated patients is lower compared to operated patients,
the two year survival rate is steady.
PMID- 29946741
TI - Ocular surface injury after shoulder surgery in the beach-chair position.
AB - PURPOSE: During shoulder surgery in the beach-chair position, head fixation can
sometimes cause rare complications. The authors share their experience in
treating ocular injury due to improper head fixation during surgery in the beach
chair position. METHODS: The study investigated consecutively 6075 patients who
underwent shoulder surgery in the beach-chair position between March 2007 and
March 2016, those patients who saw an ophthalmologist with a complaint of post
operative ocular discomfort. In the beach-chair position, surgery is performed
with the patient's upper body raised by 70 degrees . RESULTS: A total of seven
patients saw an ophthalmologist due to post-operative ocular discomfort, and a
total of five patients (0.082%) had corneal abrasion. Three of these patients
underwent arthroscopic surgery, and the other two underwent open surgery. The
mean surgery duration for the five patients was 45.0 +/- 14.68 minutes. Of these
patients, four were male and one was female, and their average age was 46 +/-
22.24 years (range: 18-69 years). All patients complained of unbearable
ophthalmodynia immediately after surgery that was not resolved using analgesics.
The ophthalmodynia resolved immediately after wearing corneal protective lenses.
CONCLUSION: Unlike typical surgery, when shoulder surgery is performed in the
beach-chair position, there is a risk of ocular surface injury due to improper
head fixation; one manifestation of this problem is corneal injury. If a severe
ophthalmodynia that cannot be controlled using analgesics occurs immediately
after surgery in the beach-chair position, a corneal injury should be suspected,
and the patient should wear a corneal protective lens. LEVEL OF EVIDENCE: Level
IV.
PMID- 29946743
TI - Complete genome sequence and phylogenetic analysis of spring viremia of carp
virus isolated from leather carp (Cyprinus carpio nudus) in Korea in 2016.
AB - Spring viremia of carp (SVC) is listed as a notifiable viral disease by the World
Organization for Animal Health (OIE). In 2016, the first official SVC outbreak
was detected in the city of Gyeongsan, Korea. The present study reports the first
complete genome analysis of SVC virus (SVCV, ADC-SVC2016-5) isolated from leather
carp (Cyprinus carpio nudus). The results revealed that ADC-SVC2016-5 has a
11,029-bp genome containing five genes: N, P, M, G, and L. Phylogenetic analysis
indicated that ADC-SVC2016-5 (accession number MG663512), isolated from leather
carp, was closely related to genogroup Ia isolates of the Asian clade. This
report provides additional information for studying the molecular epidemiology
and evolution of spring viremia of carp virus.
PMID- 29946742
TI - Dissecting the inflammatory response in polymyalgia rheumatica: the relative role
of IL-6 and its inhibition.
AB - The efficacy of tocilizumab (TCZ), a monoclonal antibody to the interleukin (IL)
6 receptor, in suppressing disease activity in glucocorticoid-naive patients with
new-onset polymyalgia rheumatica (PMR) was studied. Its effect on a panel of
cytokines and growth factors was evaluated. Three patients, fulfilling the PMR
ACR/EULAR criteria, received TCZ at the dosage of 8 mg/kg every 4 weeks for three
times followed by prednisone 0.2 mg/kg in case of inefficacy. Concentrations of
IL-10, IL-6, tumour necrosis factor (TNF)-alpha, IL-1beta, IL-10, IL-17,
interferon (IFN)-gamma, vascular endothelial growth factor (VEGF), platelet
derived growth factor (PDGF), and leukaemia inhibitory factor (LIF) were measured
at baseline, after 72 h of the first TCZ infusion and then at weeks 1, 4, 5, 8,
9, 12, 13, 14, 16, and 22. A slight clinical improvement was seen only after the
first TCZ infusion, but was largely inferior to that of conventional doses of GC
administered subsequently. An ischaemic visual accident suggestive of GCA
occurred in one patient during TCZ treatment. IL-6 was increased at baseline
compared to controls, further increased after the first TCZ infusion, and was
suppressed by GC. IL-17 production decreased during TCZ treatment and reverted to
pre-treatment levels after GC. VEGF e PDGF showed a less constant pattern, but an
increase of VEGF concentration antedated visual symptoms. The other cytokines
were not detectable in patients and controls. In our small sample, TCZ was not
able to suppress inflammation at the same degree as GC. As a result, monotherapy
with TCZ in PMR cannot be recommended, although its efficacy as adjunctive
treatment in GC-resistant patients should be further evaluated.
PMID- 29946744
TI - Bio-succinic acid production from coffee husk treated with thermochemical and
fungal hydrolysis.
AB - Coffee husk (CH), a waste obtained from processing of coffee cherries via dry
method, causes serious environmental problems. In this study, strategies were
designed to utilize CH for succinic acid (SA) production. Three different CH
hydrolysis methods: thermal, thermochemical and crude enzymes obtained by solid
state fermentation of Aspergillus niger and Trichoderma reesei, were evaluated to
generate fermentable feedstock for SA production using Actinobacillus
succinogenes. The feasibility of these pretreatment methods was investigated.
Accordingly, thermochemical hydrolysis using H2SO4 at 121 degrees C for 30 min,
appeared the most effective method for CH hydrolysis, producing 24.4 g/L of
reducing sugars (RS). Finally, 19.3 g/L of SA with yield and productivity of 0.95
g SA/g RS and 0.54 g/L/h, respectively, were obtained using CH hydrolysate. The
current study revealed an alternative way of utilization coffee waste for value
addition while mitigating environmental problems caused by its disposal.
PMID- 29946745
TI - Strain selection of microalgae isolated from Tunisian coast: characterization of
the lipid profile for potential biodiesel production.
AB - Microalgae could be of importance for future biodiesel production as an
alternative for a third generation of biofuels. To select the most appropriate
strain for biodiesel production, three microalgae species, namely Isochrysis sp.,
Nannochloropsis maritima and Tetraselmis sp., isolated from Tunisian coast, were
biochemically characterized. Initially, gas chromatography analysis showed that
Isochrysis sp. and N. maritima contained 5- and 10-fold total fatty acids,
respectively, more than Tetraselmis sp. Then, the two microalgae Isochrysis sp.
and N. maritima were subject to random mutagenesis using ultraviolet-C radiation.
Subsequently, a total of 18 mutants were obtained from both species. The neutral
lipid evaluation on said 18 mutants allowed the retention of only 7 to further
fatty acid characterization. Finally, gas chromatography revealed that the mutant
5c Isochrysis sp. was characterized by a high level of saturated fatty acids
(52.3%), higher amount of monounsaturated fatty acids (29.3%), lower level of
polyunsaturated fatty acids (18.4%) and a significant 1.3-fold increase in its
C16-C18 content compared to the wild-type strain, which would make it an
interesting candidate for biofuel production.
PMID- 29946746
TI - Non-enzymatic electrochemical glucose sensor based on monodispersed stone-like
PtNi alloy nanoparticles.
AB - Monodisperse stone-like PtNi alloy nanoparticles (NPs) were synthesized at room
temperature using an inverse microemulsion method. The results of XRD, HRTEM, and
EDS demonstrate that these NPs consist of a disordered alloy that has (a) a face
centered cubic structure, (b) Pt/Ni atomic ratios of ~5:1, and (c) a large number
of atoms exposed on the NP surface and enclosed by low index facets. The material
was placed on a glassy electrode which then displayed superior response to
glucose. Best operated at a potential of 0.43 V (vs. SCE), the electrode has the
following features: (a) a wide linear range (from 0.5 mM to 40 mM), (b) rapid
response (<1 s), (c) a low detection limit (0.35 MUM) and (d) a sensitivity of
40.17 MUA mM-1cm-2). The NP sensor also is fairly selective over ascorbic acid,
uric acid and fructose. The sensor has repeatability and durability for up to 30
days after manufacture. Graphical abstract Non-enzymatic glucose sensor based on
a glassy carbon electrode modified with PtNi-NPS enclosed by low index facets.
The sensor exhibits excellent features towards detecting glucose.
PMID- 29946747
TI - Preclinical Rheumatoid Arthritis and Rheumatoid Arthritis Prevention.
AB - PURPOSE OF REVIEW: This review is to provide an update on the current
understanding of rheumatoid arthritis (RA) development related to disease
development prior to the onset clinically apparent synovitis and opportunities
for disease prevention. RECENT FINDINGS: A growing number of studies have
demonstrated that serum elevations of autoantibodies rheumatoid factor and
antibodies to citrullinated protein/peptide antigens (ACPA) are highly predictive
of future development of IA/RA. This has underpinned the development of several
prevention trials in RA. The full results from most of these prevention trials
are pending, but ultimately, they should further inform several critical issues
in RA prevention including identification and enrollment of individuals at high
risk of imminent RA, the efficacy, safety and cost-effectiveness of prevention,
and potentially the identification of new targets for prevention. Results from
studies in RA prevention as well as other ongoing natural history studies of RA
will help to change the paradigm of how RA is managed, potentially adding
prevention to the possibilities for management.
PMID- 29946748
TI - Major and trace elements' concentrations in hard and soft tissues of kutum,
Rutilus kutum, from the Caspian Sea and their potential use as biomonitoring
tools.
AB - The potential use of different hard and soft parts (otolith, scale, eye lens,
dorsal spine, vertebral bone, muscle, and liver) of Rutilus kutum for
biomonitoring of 13 major and trace elements (Br, Ca, Cl, Cu, Fe, K, Mg, Mn, Na,
P, S, Sr, and Zn) was evaluated, for the first time. The specimens were sampled
from three sampling sites in the Southern Caspian Sea in May 2016. Twenty
specimens were collected from each site. The elements' concentrations in the
samples were measured by proton-induced X-ray emission (PIXE). In all the hard
tissues, except for eye lens, Ca was the most abundant element, whereas Fe was
among the least abundant elements. The orders of element occurrence in the two
soft tissues were largely similar. Ca, Fe, S, Cl, and K could be detected in all
the selected tissues, while Br was detectable only in otolith. Minor similarities
among the tissues were identified in the case of eye lens (concerning P, S, and
Zn) and liver (in terms of Cl, Fe, and K), whereas, in the case of Sr and Ca,
otolith shows the maximum distance. In general, it can be concluded that all the
studied hard parts, except for eye lens, may offer alternatives for biomonitoring
of Ca, Cl, Fe, K, and S in the southern Caspian Sea. The scales and spines
represent a potential non-lethal alternative to the other hard parts.
PMID- 29946750
TI - Correction to: BrdU/EdU dual labeling to determine the cell-cycle dynamics of
defined cellular subpopulations.
AB - In the original publication of the article, two errors were made in describing
the equations for Tc.
PMID- 29946749
TI - A rare case of secondary small bowel volvulus laparoscopically repositioned:
literature review and classification.
AB - BACKGROUND: Secondary small bowel volvulus is a rare condition caused by
adhesions after laparotomy or tumors. There are no clear guidelines for
indication of laparoscopic surgery. CASE PRESENTATION: A 69-year-old male visited
our hospital complaining of epigastric pain. He had a history of hypopharyngeal
carcinoma treated via pharyngolaryngoesophagectomy with restoration of esophageal
continuity by harvesting a free jejunal autograft 6 years ago. Enhanced computed
tomography revealed the whirl sign. An emergency laparoscopic operation was
performed following a diagnosis of small bowel volvulus. This revealed rotation
of the whole small bowel, involving the superior mesenteric artery as the center,
and originating at the adhesion of the proximal and distal small bowel.
Laparoscopic manipulation of volvulus and lysis of the adhesion were performed.
The patient's postoperative course was uneventful, and he was discharged on
hospital day 5. CONCLUSIONS: Laparoscopic surgery may be useful for treating
small bowel volvulus; however, the patient's treatment indications should be
judged carefully.
PMID- 29946752
TI - Comment on "Improvement of Body Composition and Quality of Life Following
Intragastric Balloon".
PMID- 29946751
TI - Examining Changes in Prevention Guidelines in Maternal and Child Health:
Development of a Teaching Activity.
AB - Purpose Recent changes in preventive guidelines (e.g., pap testing, mammography)
have resulted in confusion for both providers and patients. These changes have
occurred either because new research has been introduced or because evidence for
the practice is not established. Public health has the responsibility to promote
the dissemination and implementation of changing guidelines into practice to
improve the public's health. Health literacy may facilitate this process. The
purpose of this study is to describe a teaching tool applying principles of
health literacy to changes in prevention guidelines. The objectives of the
teaching activity were to: (1) understand the development of evidence-informed
prevention guidelines; and (2) use health literacy to evaluate the target
population's perspectives on the guideline change using a health literacy
approach. Description An interactive lecture and a practice-based assignment were
created; the assignment was pilot-tested in graduate Women's Health classes.
Multiple final products were developed in order to facilitate the lecture and
assignment: (1) lesson plan; (2) slide presentation; (3) health literacy
interview guide worksheet; and (4) grading rubric. After the presentation,
students interviewed women from the guideline target population using health
literacy constructs and synthesized their findings to create an overall
assessment report. Assessment Feedback from the pilot test informed the revision
of the teaching activity. Conclusions This teaching tool can be applied in a wide
variety of settings in higher education, such as courses in public health,
nursing, or medicine. As health literacy continues to be an important determinant
of health status, integrating this determinant into the dissemination and
communication of preventive guideline changes is needed.
PMID- 29946753
TI - Attention to Technical Details Is Important for Best Outcomes with One
Anastomosis Gastric Bypass.
PMID- 29946754
TI - [Factors influencing professional decision making on acute hospital referral in
the case of elderly patients with cognitive impairment among general
practitioners (GPs) in The Netherlands: a qualitative study].
AB - BACKGROUND: Elderly patients with cognitive impairment have a limited life
expectancy and are often acutely admitted to the hospital. Hospitalization can
negatively affect their quality of life. More knowledge on considerations prior
to these referrals is needed to improve care for these patients. AIM: The aim of
this research is to describe the aspects that can relate to the process of
referring to the hospital in the acute situation by GPs in the case of elderly
patients with cognitive impairment. METHOD: Semi-structured interviews with 21
GPs from The Netherlands were conducted and afterwards transcribed verbatim. From
these transcripts categories were extracted by using 131 focused codes according
to the grounded theory. RESULTS: Twelve categories were constructed. Six
categories relate to whether it is desirable to treat or refer. These are the
illness itself, the patient's wishes, the condition of the patient, the patient's
burden, the possibilities in the hospital, and the vision of the GP. Six
categories relate to the options available to the GP. These include medical
options, care options, available time and information, the support available to
the GP, and referrals without involvement of the GP. CONCLUSION: The referral of
elderly patients with cognitive impairment is a complex process that is
influenced by different types of factors. With these findings, specialists in
hospitals, GPs, and policy makers can improve the quality of care for this group.
PMID- 29946755
TI - Frailty modifications and prognostic impact in older patients admitted in acute
care.
AB - BACKGROUND: Frailty is a predictor of adverse outcomes in older subjects. AIMS:
The aims of this study are to (1) measure the frailty status and its changes
occurring during the hospital stay, (2) determine the relationships among frailty
and adverse outcomes. METHODS: Frailty was assessed using a 46-item Frailty Index
(FI) in 156 patients admitted to an Acute Geriatric Medicine Unit. The FI was
calculated within 24 h from the hospital admission (aFI) and at his/her discharge
(dFI). Patients were followed up to 12 months after the hospital discharge.
RESULTS: A statistically significant difference was reported between the aFI
(0.31, IQR 0.19-0.44) and the dFI (0.29, IQR 0.19-0.40; p = 0.04). The aFI was
directly associated with the risk of in-hospital death (OR = 5.9; 95% CI 2.0
17.5; p = 0.001), 1 year mortality (OR = 5.5, 95% CI 2.4-12.7, p < 0.001) and re
hospitalization (OR = 6.3, 95% CI 2.2-17.9, p = 0.03). CONCLUSION: Frailty is a
strong predictor of negative endpoints in hospitalized older persons. DISCUSSION:
Frailty assessment from routinely collected clinical data may provide important
insights about the biological status of the individual and promote the
personalization of care.
PMID- 29946756
TI - Effects of vitamin D supplementation on metabolic and endocrine parameters in
PCOS: a randomized-controlled trial.
AB - PURPOSE: Vitamin D status may be associated with insulin resistance and other key
features of polycystic ovary syndrome (PCOS), but data from preliminary
randomized controlled trials (RCTs) are conflicting. Therefore, we aimed to
investigate the effects of vitamin D supplementation on plasma glucose area under
the curve (AUCgluc, primary outcome measure) and on other metabolic and endocrine
parameters (secondary outcome measures). METHODS: This study was a single-center,
double-blind, randomized placebo-controlled trial conducted between December 2011
and July 2017 at the Medical University of Graz, Austria. One-hundred and eighty
women with PCOS and 25-hydroxyvitamin D [25(OH)D] concentrations < 75 nmol/L were
randomized in a 2:1 ratio to either receive 20,000 IU of cholecalciferol weekly
or placebo over 24 weeks. Primary outcome was the between-group difference in
AUCgluc at study end while adjusting for baseline values. RESULTS: In total, 123
participants completed the study [age 25.9 +/- 4.7 years; BMI 27.5 +/- 7.3 kg/m2;
baseline 25(OH)D 48.8 +/- 16.9 nmol/L, baseline fasting glucose 84 +/- 8 mg/dL].
Vitamin D supplementation lead to a significant increase in 25(OH)D [mean
treatment effect 33.4 nmol/L; 95% confidence interval (CI) 24.5 to 42.2; p <
0.001] but had no significant effect on AUCgluc (mean treatment effect - 9.19;
95% CI - 21.40 to 3.02; p = 0.139). Regarding secondary outcome measures, we
observed a significant decrease in plasma glucose at 60 min during oral glucose
tolerance test (mean treatment effect - 10.2 mg/dL; 95% CI - 20.2 to - 0.3; p =
0.045). CONCLUSIONS: Vitamin D supplementation had no significant effect on
metabolic and endocrine parameters in PCOS with the exception of a reduced plasma
glucose during OGTT.
PMID- 29946757
TI - Social inequality and fractures-secular trends in the Danish population: a case
control study.
AB - : We examined links between markers of social inequality and fracture risk in the
Danish population, demonstrating that high income and being married are
associated with a significantly lower risk. INTRODUCTION: We explored whether the
risk of hip, humerus, and wrist fracture was associated with markers of
inequality using data from Danish health registries. METHODS: All patients 50
years or older with a primary hip (ICD10 S720, S721, S722, and S729) humerus
(ICD10 S422, S423, S424, S425, S426, and S427), or wrist (ICD10: S52) fracture
were identified from 1/1/1995 to 31/12/2011. Fracture patients were matched 1:1
by age, sex, and year of fracture, to a non-fracture control. Markers of
inequality were as follows: income (fifths); marital status (married, divorced,
widowed, or unmarried); area of residence (remote, rural, intermediate, or
urban). Conditional logistic regression was used to investigate associations
between these exposures, and risk of fracture, adjusting for covariates (smoking,
alcohol, and Charlson co-morbidity). Interactions were fitted between exposure
and covariates where appropriate. RESULTS: A total of 189,838 fracture patients
(37,500 hip, 45,602 humerus, and 106,736 wrist) and 189,838 controls were
included. Mean age was 73.9 years (hip), 67.5 years (humerus), and 65.3 years
(wrist). High income (5th quintile) was significantly associated with a lower
odds ratio of all three fractures, compared to average income (3rd quintile).
Married subjects had a significantly decreased odds ratio across all three
fractures. However, no overall secular difference was observed regarding the
influence of the markers of inequality. CONCLUSION: In conclusion, we have
demonstrated important, stable associations between social inequality, assessed
using income, marital status, and area of residence, and fracture at the
population level. These findings can inform approaches to healthcare, and suggest
that much thought should be given to novel interventions aimed especially at
those living alone, and ideally societal measures to reduce social inequality.
PMID- 29946758
TI - Systematic approach for the formulation and optimization of atorvastatin loaded
solid lipid NANOAPARTICLES using response surface methodology.
AB - Atorvastatin is a lipid lowering agent with poor oral bioavailability (12%)
because of poor solubility and extensive first pass hepatic metabolism. In order
to overcome these issues, atorvastatin loaded solid lipid nanoparticles (ATOR
SLNs) were prepared by using glyceryl tripalmitate as lipid carrier, poloxamer
407 as surfactant and soya lecithin as emulsifier. The purpose of this work was
to optimize the formulation with the application of response surface methodology
to improve the physicochemical properties. The central composite rotatable design
consisting of three factored factorial design with three levels was used for the
optimization of the formulations. The optimized formulation was composed of
drug/lipid ratio of 1:3.64, surfactant concentration of 1.5% with 5 min time for
sonication. Fourier transforms infrared (FTIR) spectroscopy and differential
scanning calorimetry (DSC) studies confirmed the compatibility of drug and lipid
in the formulation. The optimized ATOR- SLNs showed almost spherical shape with a
mean particle size of 338.5 nm, zeta potential of -24.7mV, DL of 17.7% and EE of
81.06% respectively. The in vitro drug release study showed a burst release at
the initial stage followed by the prolongation of drug release from lipid matrix.
Stability study revealed that ATOR-SLNs were more stable at 4+/-2C when compared
with storage at 25+/-2C/60+/-5% RH during the six months storage period. These
results indicated that the developed ATOR-SLNs is a promising approach for
increment of bioavailability by improving the physicochemical properties.
PMID- 29946759
TI - Magnetic-activated cell sorting of non-apoptotic spermatozoa improves the quality
of embryos according to female age: a prospective sibling oocyte study.
AB - PURPOSE: The main aim of our study was to evaluate the benefit of the use of non
apoptotic spermatozoa selected by magnetic-activated cell sorting (MACS) for ICSI
procedures for couples in which the women had good prognoses and the male factor
of infertility was teratozoospermia. METHODS: Twenty-six couples were treated
with ICSI after MACS selection of non-apoptotic spermatozoa following a sibling
oocyte approach. Half of the oocytes were microinjected with conventionally
prepared spermatozoa, and the other half were microinjected with non-apoptotic,
MACS-selected spermatozoa. To assess the influence of MACS selection of
spermatozoa on the outcomes of the ICSI cycles, the fertilization, embryo
quality, pregnancy, and delivery rates were evaluated and compared between the
sibling oocyte groups. RESULTS: When subpopulations of couples according to
female age were analyzed, a significant difference in quality of blastocyst was
observed. More precisely, in a group that was treated with MACS-ICSI, a higher
percentage of good quality blastocysts was found among women older than 30 years
(75.0 vs. 33.3%; P = 0.028), while there was no difference among younger women.
If all included couples were compared regardless of age, no significant
difference was observed in the outcome of the ICSI/MACS-ICSI cycles in terms of
oocytes and embryos. Additionally, after the ICSI and MACS-ICSI procedures, the
morphologies of the prepared spermatozoa were compared. Results showed that the
overall percentage of morphologically normal spermatozoa did not differ
significantly between the ICSI and MACS-ICSI procedures. However, detailed
analyses of the morphologically abnormal spermatozoa revealed significantly more
spermatozoa with abnormal tails after MACS-ICSI procedure, which may be potential
consequence of the selection procedure. Moreover, the trends towards less
spermatozoa with abnormal heads and towards more spermatozoa with abnormal necks
and midpieces after MACS-ICSI procedure were revealed, although the differences
were not significant. CONCLUSIONS: Couples dealing with male infertility due to
teratozoospermia can benefit from MACS selection of spermatozoa with higher
percentage of good quality blastocysts but only when the woman is older than 30
years.
PMID- 29946761
TI - Effects of Diabetes Mellitus and Admission Glucose in Patients Receiving
Mechanical Thrombectomy: A Systematic Review and Meta-analysis.
AB - BACKGROUND: We performed a meta-analysis to evaluate the outcomes of acute
ischemic stroke (AIS) in patients treated with mechanical thrombectomy (MT),
according to diabetes mellitus and admission glucose level (AGL). METHODS: We
systematically reviewed previous studies in PubMed that reported outcomes of MT
in AIS patients and their relationships with diabetes mellitus or AGL. We used
functional independence (modified Rankin score <= 2 at 3 months) as the primary
end point. RESULTS: Data from 12,653 patients in 47 articles that evaluated the
effect of diabetes mellitus or AGL on outcomes after MT were included. Compared
with patients without a history of diabetes mellitus, patients with a diabetes
mellitus history had significantly lower odds of functional independence in both
the unadjusted meta-analysis (odds ratio [OR] 0.64; 95% confidence interval [CI]
0.54-0.75) and the multivariable analysis (OR 0.48; 95% CI 0.33-0.71). Similarly,
higher AGL was associated with an unfavorable functional outcome in the
unadjusted meta-analysis (pooled effect size - 0.38; 95% CI - 0.45 to - 0.31),
and the adjusted OR (95% CI) per 1 mmol/L increase in AGL was 0.87 (0.83-0.92)
for functional independence according to the combined multivariable results.
Recanalization rate and symptomatic intracranial hemorrhage were neither related
to AGL nor different in patients with or without diabetes mellitus. CONCLUSIONS:
The present study confirms that a history of diabetes mellitus and high AGL are
associated with unfavorable functional outcomes at 3 months after MT in AIS
patients. However, the causal relationship between hyperglycemia and poor
prognosis remains undetermined, and further investigations are required to
ascertain whether AIS patients receiving MT could benefit from intensive glucose
control.
PMID- 29946760
TI - Endometriosis does not affect live birth rates of patients submitted to assisted
reproduction techniques: analysis of the Latin American Network Registry database
from 1995 to 2011.
AB - PURPOSE: The purpose of this study is to compare the results of ART treatment in
patients with and without endometriosis in a large cohort of patients from
different centers over an extented period of time. METHODS: This retrospective
study is using data from patients undergoing 27,294 cycles of IVF/ICSI treatment
between 1995 and 2011 that were registered in the database of the Latin American
Registry maintained by the Latin America Network of Assisted Reproduction.
RESULTS: The mean number of retrieved oocytes was higher in the control group,
but the mean number of metaphase II oocytes was similar. Fertilization rate and
transfer rate were higher in the control group. We observed higher pregnancy
rates, per cycle initiated and per embryo transfer and higher live birth rate in
the endometriosis group. In the group of patients with 25-35 years old, the
number of oocytes, fertilization rate, and number of transferred embryos were
significantly higher in the control group. However, pregnancy rate and live birth
rate were higher in the endometriosis group. In the group of patients with 36-40
years old, the number of transferred embryos was higher in the control group, but
the pregnancy rate and live birth rate were higher in the endometriosis group. In
the group of patients with 41 to 42 years old, the number of transferred embryos
and the transfer rate were higher in the control group, but the pregnancy rate
was higher in the endometriosis group. CONCLUSION: Our results demonstrate that
endometriosis does not affect the outcome of patients subjected to IVF/ICSI and
although patients with endometriosis present lower number of oocytes and higher
cancelation rate, these shortcomings do not reduce pregnancy and live birth
rates.
PMID- 29946762
TI - Age-dependent effects of homocysteine and dimethylarginines on cardiovascular
mortality in claudicant patients with lower extremity arterial disease.
AB - The association among serum homocysteine (HCY), symmetric dimethylarginine
(SDMA), and asymmetric dimethylarginine (ADMA) is of interest in endothelial
dysfunction, although the underlying pathology is not fully elucidated. We
investigated the relationship of HCY with SDMA and ADMA regarding their long-time
outcome and the age dependency of HCY, SDMA, and ADMA values in claudicant
patients with lower extremity arterial disease. 120 patients were included in a
prospective observational study (observation time 7.96 +/- 1.3 years) with
cardiovascular mortality as the main outcome parameter. Patients with
intermittent claudication prior to their first endovascular procedure were
included. HCY, SDMA, and ADMA were measured by high-performance liquid
chromatography. Cutoff values for HCY (<=/>15 umol/l), SDMA (<=/>0.75 umol/l),
and ADMA (<=/>0.8 umol/l) differed significantly regarding cardiovascular
mortality (p < 0.001, p < 0.001, p = 0.017, respectively). Age correlated
significantly with HCY (r = 0.393; p < 0.001), SDMA (r = 0.363; p < 0.001), and
ADMA (r = 0.210; p = 0.021). HCY and SDMA (r = 0.295; p = 0.001) as well as SDMA
and ADMA (r = 0.380; p < 0.001) correlated with each other, while HCY and ADMA
did not correlate (r = 0.139; p = 0.130). Patients older than 65 years had higher
values of HCY (p < 0.001) and SDMA (p = 0.01), but not of ADMA (p = 0.133). In
multivariable linear regression, age was the only significant independent risk
factor for cardiovascular death (beta coefficient 0.413; 95% CI 0.007-0.028; p =
0.001). Age correlated significantly with HCY, SDMA, and ADMA. However, only age
was an independent predictor for cardiovascular death. Older patients have higher
values of HCY and SDMA than younger subjects suggesting age-adjusted cutoff
values of HCY and SDMA due to strong age dependency.
PMID- 29946763
TI - Leishmania donovani molecules recognized by sera of filaria infected host
facilitate filarial infection.
AB - We earlier found that F6 fraction of human filaria Brugia malayi cross-reacted
with sera of Leishmania donovani infected hamsters and immunization with F6
inhibited both filarial and leishmanial infections. In the present study, we
identified a 52.9-93.6 kDa fraction (Ld1) of L. donovani that cross-reacted with
sera of B. malayi infected animals and investigated effect of Ld1 on filarial
infection. Immunization of BALB/c mice with Ld1 facilitated B. malayi infection
with remarkable increase in parasite burden. Facilitation of filarial infection
was associated with downregulated cell proliferation, IL-5, IL-13, IFN-gamma, TNF
alpha, and IL-2 levels and upregulated IL-4 and TGF-beta. Ld1 exposure also
suppressed MHC class-I, MHC class-II, and FcepsilonR1 expression, and
phagocytosis in naive mouse macrophages, and CD4+, CD8+, and CD19+ cell
population in mouse spleen. Two-dimensional electrophoresis and matrix-assisted
laser desorption ionization-time of flight-mass spectrometry revealed eight
proteins in Ld1: putative heat shock protein (HSP) 70-related protein 1, HSP70
mitochondrial precursor, alanine aminotransferase, 2,3-bisphosphoglycerate
independent phosphoglycerate mutase, protein disulfide isomerase, putative ATPase
beta subunit, trypanothione reductase, and a hypothetical protein. HSP70 protein
mitochondrial precursor and trypanothione reductase showed homology with
Trypanosoma cruzi and L. donovani, respectively, and the rest 6 proteins
including hypothetical protein bear homology with L. infantum. In conclusion, the
present study for the first time shows that immunization with filarial cross
reactive Ld1 fraction of L. donovani facilitates filarial infection by modulating
Th1 and Th2 responses. Ld1 molecules may therefore facilitate filarial infection
in filaria-leishmania co-infection.
PMID- 29946764
TI - A new species of Wallinia Pearse, 1920 (Digenea: Allocreadiidae) collected from
Astyanax fasciatus (Cuvier, 1819) and A. lacustris Lucena and Soares, 2016
(Characiformes: Characidae) in Brazil based on morphology and DNA sequences.
AB - Wallinia brasiliensis n. sp. is described from the intestine of two species of
tetras-Astyanax fasciatus (Cuvier, 1819) and Astyanax lacustris Lucena and
Soares, 2016-collected from the Batalha River in Sao Paulo State, Brazil. The new
species can be clearly distinguished from the other three congeneric species by
its vitelline follicles extending from the genital pore to the end of the caeca,
eggs lacking operculum, a larger egg size with a consequently lower number
relative to the other three species, and the ovary located opposite the anterior
testis. The validity of the new species was confirmed through a phylogenetic
analysis of the 28S rRNA gene which showed that the new species is the sister
taxon to Wallinia mexicana Perez-Ponce de Leon, Razo-Mendivil, Mendoza-Garfia,
Rubio-Godoy and Choudhury, 2015, a species infecting Astyanax mexicanus (De
Filippi, 1853) in Mexico.
PMID- 29946765
TI - Prevalence of Cryptosporidium, Blastocystis, and other opportunistic infections
in patients with primary and acquired immunodeficiency.
AB - Intestinal opportunistic infections are often caused by unicellular parasites.
Individuals with decreased immunity are particularly susceptible to infection by
said microorganisms, and when they are infected, diarrhea can be the main
clinical manifestation. However, intestinal parasites have rarely been taken into
account in intestinal disorders. In our study, an investigation was conducted to
determine the prevalence of intestinal micro-pathogens, such as Cryptosporidium,
Giardia, Blastocystis, and microsporidia, in hospitalized patients with different
immunological statuses. The study at hand indicates that protozoan parasitic
infections are rare among immunodeficient patients in Poland. The overall
prevalence of micro-pathogens among participants was 4.6%; it was three times
higher in adults (12.5%) than in children (2.3%). Cryptosporidium and Cyclospora
species (Apicomplexa) were diagnosed as the main cause of heavy diarrhea.
Accordingly, adult patients were positive mainly for Blastocystis and
microsporidia, while children were more often infected with the Cryptosporidium
species.
PMID- 29946766
TI - Sorafenib and praziquantel synergistically attenuate Schistosoma japonicum
induced liver fibrosis in mice.
AB - Liver fibrosis is an important process that occurs in most types of chronic liver
diseases and often results in the end stage of liver diseases, such as cirrhosis,
portal hypertension, and hepatocellular carcinoma. Sorafenib, a multiple tyrosine
kinase inhibitor, has been shown to inhibit liver fibrosis in multiple
experimental fibrosis mouse and rat models. The aim of this study was to test the
therapeutic effect of sorafenib on liver fibrosis induced by infection with a
parasite, Schistosoma japonicum, in mice. Mice were percutaneously infected
through the abdomen with Schistosoma cercariae to develop a schistosomula liver
fibrosis model. Eight weeks after infection, infected mice were treated with the
anti-parasitic agent praziquantel for 2 days and sorafenib for 2 weeks. Hepatic
histopathological changes were assessed using hematoxylin and eosin (HE) and
Masson's trichome staining. The hepatic expression levels of collagen I, collagen
III, alpha-smooth muscle actin (alpha-SMA), platelet-derived growth factor
(PDGF), and PDGF receptor-beta (PDGFR-beta) were analyzed by immunohistochemistry
and western blot. Praziquantel administration alone but not sorafenib reduced
liver fibrosis, and the combination of praziquantel and sorafenib significantly
attenuated liver fibrosis in S. japonicum-infected mice. Moreover, sorafenib plus
praziquantel markedly decreased the hepatic deposition of collagen and expression
of fibrogenic genes in these mice. In conclusion, the use of sorafenib following
praziquantel treatment may represent a potential therapeutic strategy for liver
fibrosis induced by S. japonicum in patients.
PMID- 29946767
TI - Inorganic iron-sulfur clusters enhance electron transport when used for wiring
the NAD-glucose dehydrogenase based redox system.
AB - Wiring the active site of an enzyme directly to an electrode is the key to
ensuring efficient electron transfer for the proper performance of enzyme-based
bioelectronic systems. Iron-sulfur complexes, the first link between proteins and
mediating molecules in the biological electron transport chain(s), possess an
intrinsic electron transport capability. The authors demonstrate the application
of inorganic iron-sulfur clusters (Fe-S) viz. FeS, FeS2, Fe2S3, and Fe3S4, as
molecular wires to mediate electron transport between a glucose-selective redox
enzyme and the gold electrode. It is shown that Fe-S can emulate the
functionality of the natural electron transport chain. Voltammetric studies
indicate a significant improvement in electron transport, surface coverage, and
resilience achieved by the Fe-S-based glucose anodes when compared to a
conventional pyrroloquinoline quinone (PQQ)-based electrode. The Fe-S-based
glucose anodes showed glucose oxidation at a potential of +0.5 V vs. Ag/AgCl with
Tris-HCl buffer (pH 8) acting as a carrier. The current densities positively
correlated with the concentrations of glucose in the range 0.1-100 mM displaying
detection limits of 0.77 mM (FeS), 1.22 mM (FeS2), 2.95 mM (Fe2S3), and 14.57 mM
(Fe3S4). The metal-anchorable sulfur atom, the strong pi-coordinating iron atom,
the favorable redox properties, low cost, and natural abundance make Fe-S an
excellent electron-mediating relay capable of wiring redox active sites to
electrode surfaces. Graphical abstract Schematic representation of inorganic iron
sulfur clusters used as molecular wires to facilitate direct electron transfer
between NAD-glucose dehydrogenase and the gold electrode. The iron-sulfur based
glucose anodes improve current response to selectively sense glucose
concentrations in the range 0.1-100 mM.
PMID- 29946768
TI - Temporal variation in total phosphorus concentrations revealed from a
multidecadal monitoring program on Big Platte Lake, Michigan.
AB - Effective water quality management depends on enactment of appropriately designed
monitoring programs to reveal current and forecasted conditions. Because water
quality conditions are influenced by numerous factors, commonly measured
attributes such as total phosphorus (TP) can be highly temporally varying. For
highly varying processes, monitoring programs should be long-term and periodic
quantitative analyses are needed so that temporal trends can be distinguished
from stochastic variation, which can yield insights into potential modifications
to the program. Using generalized additive mixed modeling, we assessed temporal
(yearly and monthly) trends and quantified other sources of variation (daily and
subsampling) in TP concentrations from a multidecadal depth-specific monitoring
program on Big Platte Lake, Michigan. Yearly TP concentrations decreased from the
late 1980s to late 1990s before rebounding through the early 2000s. At depths of
2.29 to 13.72 m, TP concentrations have cycled around stationary points since the
early 2000s, while at the surface and depths >= 18.29 concentrations have
continued declining. Summer and fall peaks in TP concentrations were observed at
most depths, with the fall peak at deeper depths occurring 1 month earlier than
shallower depths. Daily sampling variation (i.e., variation within a given month
and year) was greatest at shallowest and deepest depths. Variation in subsamples
collected from depth-specific water samples constituted a small fraction of total
variation. Based on model results, cost-saving measures to consider for the
monitoring program include reducing subsampling of depth-specific concentrations
and reducing the number of sampling depths given observed consistencies across
the program period.
PMID- 29946769
TI - The Area method: a new method for ultrasound assessment of diaphragmatic
movement.
AB - BACKGROUND: Ultrasound can be used to assess diaphragm movement. Existing methods
focus on movement at a single point at the hemidiaphragm and may not consider the
anatomic and functional complexity. We aimed to develop an ultrasound method, the
Area method, to assess movement of the entire hemidiaphragm dome and to compare
it with existing methods to evaluate accuracy, inter-rater agreement, and
feasibility. METHODS: Movement of the diaphragm was evaluated by ultrasonography
in 19 healthy subjects and correlated with simultaneously performed spirometry.
Two existing methods, the M-mode excursion at the posterior part of diaphragm and
the B-mode at the top of the diaphragm, were compared with the Area method. Two
independent raters reviewed film clips to analyze inter-rater agreement.
Feasibility was tested by novice ultrasound operators. RESULTS: Correlation with
expired lung volume was higher with the Area method, 0.88 (95% CI 0.81-0.95), p <
0.001, and with the M-mode measurement, 0.84 (95% CI 0.75-0.92), p < 0.001, than
with the B-mode measurement, 0.71 (95% CI 0.59-0.83), p < 0.001. Inter-rater
agreement was highest with the Area method, 0.9, p < 0.001, and M-mode
measurement 0.9, p < 0.001, and lower with the B-mode measurement, 0.8, p <
0.001. The M-mode measurement could be done in only 20% at the left side. The
Area method could be performed in all participants at both hemidiaphragms, and
novice operators found it easy to perform. CONCLUSION: A new method to evaluate
diaphragm movement is introduced. Accuracy and inter-rater agreement are high.
The Area method is equally feasible at both hemidiaphragms in contrast to
existing methods. However, additional studies should include more participants,
different types of pulmonary diseases, and investigate the role of patient
position to validate the Area method fully.
PMID- 29946770
TI - Ginsenoside metabolite compound K exerts anti-inflammatory and analgesic effects
via downregulating COX2.
AB - OBJECTIVE: The present study aimed to evaluate the anti-inflammatory and
analgesic activities of the ginsenoside metabolite compound K (CK) and its
mechanisms. METHODS: Mice model of xylene-induced ear swelling and rat model of
carrageenan-induced paw swelling were used to evaluate the effect of CK on acute
inflammation. The analgesic effect of CK was evaluated on heat-, acetic acid-,
and carrageenan-induced hyperalgesia. The levels of prostaglandin E2 (PGE2),
cyclooxygenase-1 (COX-1), and COX-2 in carrageenan-induced rat paw swelling and
gastric mucosa were detected by enzyme-linked immunosorbent assay (ELISA). COX-1
and COX-2 expressions in carrageenan-induced rat paw swelling and gastric mucosa
were detected by western blotting. In vitro effect of CK (10-9, 10-8, 10-7, 10-6,
10-5 M) on COX-1 and COX-2 activities was evaluated by measuring the production
of 6-keto-PGF1alpha and PGE2 in rat peritoneal macrophages. RESULTS: CK at doses
of 7, 14, 28, 56, 112, and 224 mg/kg alleviated xylene-induced ear oedema,
whereas CK at 40, 80, and 160 mg/kg alleviated carrageenan-induced paw oedema. CK
at 224 mg/kg showed an analgesic effect against acetic acid-induced pain. CK at
40, 80, and 160 mg/kg significantly increased rat inflammatory pain threshold,
but had no effect on heat-induced pain threshold. CK at 10, 20, 40, 80, and 160
mg/kg reduced PGE2 level in the paw tissue, but showed no effect on that in the
gastric mucosa. CK at 20, 40, 80, and 160 mg/kg decreased COX-2 expression in the
paw tissue and gastric mucosa, but exhibited no effect on COX-1 expression or on
COX-1 and COX-2 activities. CONCLUSION: CK exerted anti-inflammatory and
analgesic effects, possibly by reducing the catalytic synthesis of PGE2 via
downregulation of COX-2 expression.
PMID- 29946772
TI - Glucose Metabolism in Cancer.
AB - KEY POINTS: Otto Warburg observed a peculiar phenomenon in 1924, unknowingly
laying the foundation for the field of cancer metabolism. While his
contemporaries hypothesized that tumor cells derived the energy required for
uncontrolled replication from proteolysis and lipolysis, Warburg instead found
them to rapidly consume glucose, converting it to lactate [1]. The significance
of this finding, later termed the Warburg effect, went unnoticed by the larger
scientific community at that time. The field of cancer metabolism lay dormant for
almost a century awaiting advances in molecular biology and genetics which would
later open the doors to new cancer therapies.
PMID- 29946773
TI - Glutamine Metabolism in Cancer.
AB - KEY POINTS: Metabolism is the fundamental process for all cellular functions. For
decades, there has been growing evidence with regard to the relationship between
metabolism and malignant cell proliferation. Unlike normal differentiated cells,
however, cancer cells have reprogrammed metabolisms in order to fulfill their
energy requirements. These cells display crucial modifications in many metabolic
pathways, including glucose transport, glutaminolysis which includes the
tricarboxylic acid (TCA) cycle, the electron transport chain (ETC), and the
pentose phosphate pathway (PPP) [1]. Since the discovery of the Warburg effect,
it has been shown that the metabolism of cancer cells plays a critical role in
cancer survival and growth. More recent research suggests that the involvement of
glutamine in cancer metabolism is more significant than previously thought.
Glutamine, a non essential amino acid with an amine functional group, is the most
abundant amino acid circulating in the bloodstream [2]. This chapter will discuss
the characteristic features of glutamine metabolism in cancers.
PMID- 29946775
TI - The Multifaceted Metabolism of Glioblastoma.
AB - KEY POINTS: Glioblastoma multiforme (GBM) develops on glial cells and is the most
common, as well as the deadliest, form of brain cancer [1]. As in pancreatic
cancers, distinct combinations of genetic alterations in GBM subtypes induce a
multiplicity of metabolic phenotypes, which explains the variability of GBM
sensitivity to current therapies targeting its reprogrammed metabolism.
Therefore, it is becoming imperative for cancer researchers to account for the
metabolic heterogeneity within this cancer type before making generalized
conclusions about a particular drug's efficacy against all cancers of that type.
GBMs can be classified initially into two subsets consisting of primary and
secondary GBMs, and this categorization stems from cancer development. GBM is the
highest grade of gliomas, which includes glioma I, glioma II, glioma III, and
glioma IV (GBM). Secondary GBM develops from a low-grade glioma to advanced stage
cancer, while primary GBM provides no signs of progression and is identified as
an advanced stage glioma from the onset. The differences in prognosis and
histology correlated with each classification are normally negligible, but the
demographics of individuals affected and the accompanying genetic/metabolic
properties show distinct differentiations [2].
PMID- 29946774
TI - The Heterogeneity of Lipid Metabolism in Cancer.
AB - KEY POINTS: The study of cancer cell metabolism has traditionally focused on
glycolysis and glutaminolysis. However, lipidomic technologies have matured
considerably over the last decade and broadened our understanding of how lipid
metabolism is relevant to cancer biology [1-3]. Studies now suggest that the
reprogramming of cellular lipid metabolism contributes directly to malignant
transformation and progression [4, 5]. For example, de novo lipid synthesis can
supply proliferating tumor cells with phospholipid components that comprise the
plasma and organelle membranes of new daughter cells [6, 7]. Moreover, the
upregulation of mitochondrial beta-oxidation can support tumor cell energetics
and redox homeostasis [8], while lipid-derived messengers can regulate major
signaling pathways or coordinate immunosuppressive mechanisms [9-11]. Lipid
metabolism has therefore become implicated in a variety of oncogenic processes,
including metastatic colonization, drug resistance, and cell differentiation [10,
12-16]. However, whether we can safely and effectively modulate the underlying
mechanisms for cancer therapy is still an open question.
PMID- 29946776
TI - The Intricate Metabolism of Pancreatic Cancers.
AB - KEY POINTS: Currently, approximately 95% of pancreatic cancers are pancreatic
ductal adenocarcinoma (PDAC), which is the most aggressive form and the fourth
leading cause of cancer death with extremely poor prognosis [1]. Poor prognosis
is primarily attributed to the late diagnosis of the disease when patients are no
longer candidates for surgical resection [2]. Cancer cells are dependent on the
oncogenes that allow them to proliferate limitlessly. Thus, targeting the
expression of known oncogenes in pancreatic cancer has been shown to lead to more
effective treatment [3]. This chapter will discuss the complexity of metabolic
features in pancreatic cancers. To be able to fully comprehend the heterogeneous
nature of cancer metabolism, we need to take into account the close relationship
between cancer metabolism and genetics. Gene expression varies tremendously, not
only among different types of cancers, but also within the same type of cancer
among different patients. Cancer metabolism heterogeneity is often prompted and
perpetuated not only by genetic mutations in oncogenes and tumor suppressor genes
but also by the innate diversity of the tumor microenvironment. Much effort has
been focused on elucidating the genetic alterations that correlate with disease
progression and treatment response [4]. However, the precise mechanism by which
tumor metabolism contributes to cancer growth, survival, mobility, and
aggressiveness represents a functional readout of tumor progression.
PMID- 29946777
TI - Breast Cancer Metabolism.
AB - KEY POINTS: Despite advances in screening, therapy, and surveillance that have
improved survival rates, breast cancer is still the most commonly diagnosed
cancer and the second leading cause of cancer mortality among women [1]. Breast
cancer is a highly heterogeneous disease rooted in a genetic basis and reflected
in clinical behavior. The diversity of breast cancer hormone receptor status and
the expression of surface molecules has guided therapy decisions for decades;
however, subtype-specific treatment often yields diverse responses due to varying
tumor evolution and malignant potential. Although understanding the mechanisms
behind breast cancer heterogeneity is still a challenge, available evidence
suggests that studying its metabolism has the potential to give valuable insight
into the causes of these variations, as well as viable targets for intervention.
PMID- 29946778
TI - Non-Hodgkin Lymphoma Metabolism.
AB - KEY POINTS: Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoid
neoplasms with differing biological characteristics. About 90% of all lymphomas
in the United States originate from B lymphocytes, while the remaining originate
from T cells [1]. The treatment of NHLs depends on neoplastic histology and the
stage of the tumor, which will indicate whether radiotherapy, chemotherapy, or a
combination is the best suitable treatment [2]. The American Cancer Society
describes the staging of lymphoma as follows: Stage I is lymphoma in a single
node or area. Stage II is when that lymphoma has spread to another node or organ
tissue. Stage III is when it has spread to lymph nodes in two sides of the
diaphragm. Stage IV is when the cancer has significantly spread to organs outside
the lymph system. Radiation therapy is the traditional therapeutic route for
localized follicular and mucosa-associated lymphomas. Chemotherapy is utilized
for the treatment of large cell lymphomas and high-grade lymphomas [2]. However,
treatment of indolent lymphomas remains problematic as the patients often have
metastasis for which no standard approach exists [2].
PMID- 29946779
TI - The Metabolism of Renal Cell Carcinomas and Liver Cancer.
AB - KEY POINTS: According to data from the American Cancer Society, cancer is one of
the deadliest health problems globally. Annually, renal cell carcinoma (RCC) and
liver cancer cause more than 100,000 and 800,000 deaths worldwide, respectively
[1-4], creating an urgent need to develop effective therapeutic treatments to
increase patient survival outcomes. New therapeutic treatments are expected to
address a major factor contributing to cancer's resistance to standard therapies:
oncogenic heterogeneity. Because gene expression can vary tremendously among
different types of cancers, different patients of the same tumor type, and even
within individual tumors, various metabolic phenotypes can emerge, making single
therapy approaches insufficient. This heterogeneity translates into changes in
the landscape of metabolic enzymes and biomolecules within both the cancer cell
and tumor microenvironment. Novel strategies targeting the diverse metabolism of
cancers aim to overcome this obstacle, and though some have yielded positive
results, it remains a challenge to uncover all of the distinct metabolic profiles
of RCC and liver cancer. Nonetheless, the metabolic-oriented research focusing on
these cancers has offered different, fresh new perspectives, which are expected
to contribute heavily to the development of new therapeutic treatments.
PMID- 29946780
TI - Different Tumor Microenvironments Lead to Different Metabolic Phenotypes.
AB - KEY POINTS: The beginning of the twenty-first century offered new advances in
cancer research, including the expansion of the knowledge about the tumor
microenvironment (TME). Because TMEs provide the niches in which cancer cells,
fibroblast, lymphocyte, and immune cells reside, they play a key role in cancer
cell development, differentiation, survival, and proliferation. Throughout cancer
progression, the TME constantly evolves, causing cancer cells to adapt to the new
conditions. The heterogeneity of cancer, evidenced by diverse proliferation
rates, cellular structure, metabolism, and gene expression, presents challenges
for cancer treatments despite the advances in research. This chapter discusses
how different tumor microenvironments lead to specific metabolic adaptations
which drive cancer progression.
PMID- 29946781
TI - The Intratumoral Heterogeneity of Cancer Metabolism.
AB - KEY POINTS: Cancer is one of the deadliest diseases in the world, especially
within the past few decades, causing over half a million deaths a year in the USA
only [1]. Despite recent advances made in the field of cancer biology and the
therapies that have been developed, it is clear that more advances are necessary
for us to classify cancer as curable. The logical question that arises is simple:
Why, despite all the technologies and medical innovations of our time, has a cure
eluded us? This chapter will shed light on one of cancer's most impactful
attributes: its heterogeneity and, more specifically, the intratumoral
heterogeneity of cancer metabolism. Simply put, what makes cancer one of the
deadliest known diseases is its ability to change and adapt. Cancer cells' rapid
evolution, coupled with their irrepressible ability to divide, gives them the
advantage over our immune systems. In this chapter, we will delve into the
complexities of this adaptability and the vital role that metabolism plays in the
rise and progression of this heterogeneity.
PMID- 29946782
TI - Metabolic Relationship between Cancer-Associated Fibroblasts and Cancer Cells.
AB - KEY POINTS: Cancer-associated fibroblasts (CAFs), a major component of the tumor
microenvironment (TME), play an important role in cancer initiation, progression,
and metastasis. Recent findings have demonstrated that the TME not only provides
physical support for cancer cells, but also directs cell-to-cell interactions (in
this case the interaction between cancer cells and CAFs). As cancer progresses,
the CAFs also co evolve-transitioning from an inactivated state to an activated
state. The elucidation and understanding of the interaction between cancer cells
and CAFs will pave the way for new cancer therapies [1-3].The TME is a
heterogeneous environment consisting of fibroblasts, tumor-associated
macrophages, adipocytes, an extracellular matrix, and mesenchymal stem cells [4].
The exact composition of each stroma varies depending on cancer and tissue type.
To add to this variation, there is heterogeneity even within the CAF population
itself. Different CAFs express different markers and influence stromal pro
tumorigenic capacity and cancer progression in diverse ways [5, 6].
PMID- 29946784
TI - Comparison of Actinomycete Community Composition on the Surface and Inside of
Japanese Black Pine (Pinus thunbergii) Tree Roots Colonized by the
Ectomycorrhizal Fungus Cenococcum geophilum.
AB - Various bacteria are associated with ectomycorrhizal roots, which are symbiotic
complexes formed between plant roots and fungi. Among these associated bacteria,
actinomycetes have received attention for their ubiquity and diverse roles in
forest ecosystems. Here, to examine the association of actinomycetes with
ectomycorrhizal root tips, we compared the bacterial and actinomycete communities
on the surface and inside of root tips of coastal Japanese black pine (Pinus
thunbergii) colonized by the fungus Cenococcum geophilum. Next-generation
sequences of 16S rDNA of bacteria communities using the Ion Torrent Personal
Genome Machine showed that the number of bacterial classes in the surface of C.
geophilum ECM roots was significantly higher than that in non-ECM roots. The
bacterial community structure of surface, inside, and non-ECM roots was
significantly discriminated each other. For an isolation method, a total of 762
and 335 actinomycete isolates were obtained from the surface and inside of the
roots, respectively. In addition, the isolation ratio of actinomycetes in these
root tips varied depending on the age of the tree and the season. Identification
of the isolates based on partial 16S rDNA sequencing revealed that the isolates
belonged to nine genera of the order Actinomycetales. On the surface of the
roots, most of the isolates belonged to genus Streptomyces (90.4%); inside of the
roots, most of the isolates belonged to genus Actinoallomurus (40.0%), which is a
relatively new taxon. Our results suggest that actinomycetes as well as bacteria
are ubiquitously associated with C. geophilum ectomycorrhizal roots of P.
thunbergii, although their communities can vary either surface or inside of
individual root tips.
PMID- 29946783
TI - Targeting Metabolic Cross Talk between Cancer Cells and Cancer-Associated
Fibroblasts.
AB - KEY POINTS: Although tumorigenesis has classically been regarded as a genetic
disease of uncontrolled cell growth, the importance of the tumor microenvironment
(TME) is continuously emphasized by the accumulating evidence that cancer growth
is not simply dependent on the cancer cells themselves [1, 2] but also dependent
on angiogenesis [3-6], inflammation [7, 8], and the supporting roles of cancer
associated fibroblasts (CAFs) [9, 10]. After the discovery that CAFs are able to
remodel the tumor matrix within the TME and provide the nutrients and chemicals
to promote cancer cell growth [11], many studies have aimed to uncover the cross
talk between cancer and CAFs. Moreover, a new paradigm in cancer metabolism shows
how cancer cells act like "metabolic parasites" to uptake the high-energy
metabolites, such as lactate, ketone bodies, free fatty acid, and glutamine from
supporting cells, including CAFs and cancer-associated adipocytes (CAAs) [12,
13]. This chapter provides an overview of the metabolic coupling between CAFs and
cancer to further define the therapeutic options to disrupt the CAF-cancer cell
interactions.
PMID- 29946785
TI - Three-Dimensional Versus Two-Dimensional Video-Assisted Endoscopic Surgery: A
Meta-analysis of Clinical Data.
AB - BACKGROUND: There have been no studies to systematically evaluate the two display
(3D vs. 2D) systems regarding both laparoscopic and thoracoscopic surgeries in
clinical settings; thus, we conducted one to evaluate the safety and efficacy of
different visualization systems (two-dimensional and three-dimensional) during
endoscopic surgery (laparoscopy or thoracoscopy) in clinical settings. METHODS: A
comprehensive search of online databases was performed. Perioperative outcomes
were synthesized. Cumulative meta-analysis was performed to evaluate the temporal
trend of pooled outcomes. Specific subgroups (laparoscopy vs. thoracoscopy,
prospective vs. retrospective study, malignant vs. benign diseases) were
examined. Meta-regression was conducted to explore the source of heterogeneity.
RESULTS: Twenty-three articles were considered in this analysis, of which 7 were
thoracoscopic and 16 were laparoscopic surgeries. A total of 2930 patients were
recorded, of which 1367 underwent 3D video-assisted surgery and 1563 underwent 2D
display. Overall, significantly shorter operating time (SMD -0.69; p = <0.001),
less blood loss (SMD -0.26; p = 0.028) and shorter hospital stays (SMD -0.16; p =
0.016) were found in the 3D display group. Meanwhile, the perioperative morbidity
(OR 0.92; p = 0.487), retrieved lymph nodes (SMD 0.09; p = 0.081), drainage
duration (SMD -0.15; p = 0.105) and drainage volume (SMD 0.00; p = 0.994) were
similar between the two groups. Comparison of the overall outcomes in each subset
showed consistency in all groups. CONCLUSIONS: This up-to-date meta-analysis
reveals that the 3D display system is superior to the 2D system in clinical
settings with significantly shorter operating time, less blood loss and shorter
hospital stay. These findings suggest that, in laparoscopic or thoracoscopic
surgeries, 3D endoscopic system is preferable when condition permits. Future
efforts should be made on decreasing the side effects of 3D display and
increasing its cost-effectiveness.
PMID- 29946787
TI - Authors' Reply: Are American Surgical Residents Prepared for Humanitarian
Deployment? A Comparative Analysis of Resident and Humanitarian Case Logs.
PMID- 29946786
TI - Impact of Postoperative Pneumonia Developing After Discharge on Long-Term Follow
up for Resected Lung Cancer.
AB - BACKGROUND: Postoperative nosocomial pneumonia is a common immediate complication
following lung resection. However, the incidence and mortality of pneumonia
developing after discharge (PDAD) for lung-resected patients during long-term
observation remain unclear. The aim of this study was to investigate the clinical
features of PDAD in patients with resected lung cancer. METHODS: We conducted a
retrospective cohort study of 357 consecutive patients with lung cancer who had
undergone lung resection at a single institution, between April 2007 and December
2016. The clinical characteristics, pathological features, and overall survival
were analyzed. Propensity score matched analysis was used for the evaluation of
overall survival between PDAD and non-PDAD groups with adjusted relevant
confounding factors. RESULTS: PDAD was observed in 66 patients (18.5%). The
cumulative incidence of PDAD was 14.9% at 3 years and 21.6% at 5 years. Mortality
of PDAD was 30.3%. Multivariate analysis demonstrated that the risk factors for
PDAD were age (OR 1.07; P = 0.005), oral steroid use (OR 5.62; P = 0.046), and
lower-lobe resection (OR 1.87; P = 0.034). After propensity score matching, 52
patients with PDAD and 52 patients without it were compared. The incidence of
PDAD resulted in a worse 5-year overall survival (56.1 vs. 69.3%; P = 0.024). The
Cox proportional hazards model indicated that PDAD was associated with poor
overall survival (HR 1.99, P = 0.027). CONCLUSIONS: Our findings revealed a high
incidence and mortality of PDAD among patients who had undergone lung resection
with long-term follow-up. Therefore, PDAD could be associated with poorer overall
survival.
PMID- 29946788
TI - Stenting in Palliation of Unresectable Esophageal Cancer.
AB - BACKGROUND: The aim of this study was to analyze the safety and effectiveness of
stenting using partially covered self-expandable stents in palliation of
dysphagia in patients with unresectable esophageal cancer. METHODS: Retrospective
analysis of hospital records of all patients who underwent esophageal stenting in
the period 2008-2015 was performed. The study included patients with unresectable
esophageal and esophagogastric cancer. RESULTS: There were 442 patients included.
Mean age was 56 years (range 28-89), and 379 were males. In 40 (9.0%) patients,
stenting was performed in the cervical, in 150 (39.3%)-in the middle thoracic, in
141 (31.9%)-in lower thoracic esophagus and in 111 (25.1%)-in the esophagogastric
junction. Stenting resulted in significant alleviation of dysphagia grade (3.0
vs. 1.0, p = 0.00001). During the follow-up, 55 (12.4%) patients experienced
recurrent dysphagia due to tumor or granulation tissue overgrowth, and in 18
(4.1%) patients, migration of the stent occurred, for which an independent risk
factor was adjuvant chemo- and/or radiation therapy (p = 0.001). Minor
complications included chest pain (54.5%), delayed complete stent expansion
(12.0%), feeling of a foreign body (25.3%), hiccup (1.6%), gastroesophageal
reflux (45.6%) and post-discharge pneumonia (2.5%). A feeling of a foreign body
in the esophagus was significantly more common after stenting of the cervical
esophagus (p = 0.0001), and hiccup was more common after stenting of the
esophagogastric junction (p = 0.02). Major complications included bleeding
(1.3%), respiratory insufficiency (0.7%), esophageal perforation (0.9%) and
irregular heartburn (2.3%). Overall procedure-related mortality was 0.4%. The
median survival time was 117.8 days (range 2-732). CONCLUSIONS: Stenting is an
effective procedure in relieving dysphagia in patients with unresectable
malignant esophageal stenosis and is associated with low rate of postoperative
and long-term complications.
PMID- 29946789
TI - First Do No Harm: Predicting Surgical Morbidity During Humanitarian Medical
Missions.
AB - BACKGROUND: Despite good intentions, humanitarian surgical missions are
unavoidably linked to some degree of complication. We hypothesized that the
American College of Surgeons Surgical Risk Calculator (ACS-SRC) could estimate
the risk of complications of procedures performed during the US Navy's Pacific
Partnership 2015 (PP15) mission. METHODS: Patient information and surgical
details recorded during PP15 were entered into the ACS-SRC. Risks of
complications for each procedure were calculated. Receiver operating
characteristics and Brier scores were calculated to compare the predicted
outcomes to the observed complications. RESULTS: Of the 174 unique procedures
performed during PP15 (representing 465 patients), 99 were found in the ACS-SRC
(representing 256 patients). Risk calculations for PP15 were: 1.5% risk (IQR 0.9,
2.4) of "serious" complications and 2.0% risk (IQR 1.3, 2.8) of "any"
complication. ACS-SRC specific risks were calculated as follows: pneumonia 0.1%,
cardiac 0.0%, surgical site infection (SSI) 0.6%, urinary tract infection 0.2%,
venous thromboembolism 0.1%, renal failure 0.0%, OR return 0.9%, and death 0.0%.
The only specific ACS-SRC complication observed was "OR return" (0.35%) and SSI
(0.35%). The observed PP15 rates for "serious" or "any" complications (ACS-SRC
definition) were 0.70% (2/285) each. Receiver operating characteristics for ACS
SRC for predicting "serious" or "any" complication were 0.743 (p = 0.118) and
0.654 (p = 0.227), respectively. CONCLUSIONS: Although the ACS-SRC over-predicted
risk compared to observed outcomes, it may offer a good starting point for
humanitarian surgery risk calculation. Observed outcomes may be limited by loss
to-follow-up bias. Emphasis should be placed on establishing patient follow-up as
part of humanitarian surgical mission planning and execution.
PMID- 29946790
TI - LaMIR166a-mediated auxin biosynthesis and signalling affect somatic embryogenesis
in Larix leptolepis.
AB - Somatic embryogenesis (SE) involves complex molecular signalling pathways.
Understanding molecular mechanism of SE in Larix leptolepis (L. leptolepis) can
aid research on genetic improvement of gymnosperms. Previously, we obtained five
LaMIR166a (miR166a precursor) -overexpression embryonic cell lines in the
gymnosperm Larix leptolepis. The proliferation rates of pro-embryogenic masses in
transgenic and wild-type lines were calculated. Overexpression of the miR166a
precursor LaMIR166a led to slower proliferation. When pro-embryogenic masses were
transferred to maturation medium, the relative expression of LaMIR166a and
miR166a in the LaMIR166a-overexpression lines was higher than in the wild-type
during SE, while LaHDZ31-34 expression levels also increased without negative
control by miR166, suggesting that regulation of HD-ZIP III by miR166a exits
stage-specific characteristics. The key indole-3-acetic acid (IAA) biosynthetic
gene Nitrilase of L. leptolepis (LaNIT) was identified and the effects of miR166a
on auxin biosynthesis and signalling genes were studied. During SE, LaNIT, Auxin
response factor1 (LaARF1) and LaARF2 mRNA levels and IAA contents were markedly
higher in LaMIR166a-overexpression lines, which revealed lower deformity rate of
embryos, indicating endogenous IAA synthesis is required for somatic embryo
maturation in L. leptolepis. Additionally, the IAA biosynthesis and signalling
genes showed similar expression patterns to LaHDZ31-34, suggesting HD-ZIP III
genes have a positive regulatory effect on LaNIT. Our results suggest miR166a and
LaHDZ31-34 have important roles in auxin biosynthesis and signalling during SE,
which might determine if the somatic embryo normally developed to mature in L.
leptolepis.
PMID- 29946791
TI - Chemotherapy drug concentrations in hair follicles: a potential biomarker to
monitor the effectiveness of scalp cooling for chemotherapy-induced alopecia.
PMID- 29946792
TI - Nausea in advanced cancer: relationships between intensity, burden, and the need
for help.
AB - PURPOSE: This study aimed at expanding the knowledge of nausea in patients with
advanced cancer by elucidating (a) the prevalences of patients having nausea,
experiencing nausea as a problem, and having a need for help with their nausea,
respectively, (b) determining variables associated with nausea, and (c)
investigating the relation between nausea and the need for help regarding nausea.
METHODS: In 2004-2006, the EORTC QLQ-C30 and the Three-Levels-of-Needs
Questionnaire (3LNQ) were mailed to 2364 patients with advanced cancer who had
been in contact with one of the 54 hospital departments within the past year.
Further information was collected from medical records. RESULTS: Patient-response
rate was 61%. Twenty-two percent reported having had some degree of nausea within
the past week, with a mean nausea score of 10.4 and a two-item combined nausea
and vomiting score of 7.5 (0-100, 100 = "very much"). Factors associated with
nausea on the multivariate level were contact type (inpatient/outpatient) and
treatment status (receiving ongoing oncologic treatment yes/no). "Nausea
intensity" and "nausea problem burden" showed acceptable abilities to distinguish
between patients having or not having an unmet need for help regarding nausea
with areas under the curve (AUCs) of 0.81 and 0.82, respectively. CONCLUSIONS:
Around one in four patients with advanced cancer reported nausea within the past
week, highest in patients who were inpatients or undergoing active oncologic
treatment. Almost all patients reporting nausea on the EORTC QLQ-C30 experienced
this to be a problem, and the 3LNQ can therefore be restricted to cases where
additional details are needed.
PMID- 29946793
TI - Taurine attenuates the development of hepatic steatosis through the inhibition of
oxidative stress in a model of nonalcoholic fatty liver disease in vivo and in
vitro.
AB - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
liver disease. It is characterized by the accumulation of triglyceride within
hepatocytes. Taurine is a sulfur-containing-beta-amino acid that is widely
distributed in mammalian tissues. The objective of this study was to examine the
effects of taurine on the development of hepatic steatosis in a model of NAFLD in
vivo and in vitro. Male C57BL/6J mice were fed a high-fat diet (HFD) supplemented
with 2% (w/v) or 5% (w/v) taurine for 12 weeks. An in vitro study was performed
in HepG2 cells loaded with fatty acids. Twelve weeks of supplementation with an
HFD increased the hepatic lipid levels and oxidative stress as well as the body
weight and liver weight. Taurine significantly suppressed these changes, which
was accompanied by a decrease in the hepatic level of thiobarbituric acid
reactive substances (TBARS). In addition, taurine treatment suppressed the HFD
induced reduction of the enzyme activity of hepatic superoxide dismutase and
catalase and the reduction of the hepatic level of reduced glutathione and ATP.
In HepG2 cells, taurine suppressed the fatty acid-induced lipid accumulation,
production of reactive oxygen species and TBARS level, and amelioration of the
fatty acid-induced disruption of the mitochondrial membrane potential. These
results showed that taurine was effective in alleviating hepatic steatosis by
reducing oxidative stress. Taurine may, therefore, be of therapeutic value in
reducing the risks associated with NAFLD.
PMID- 29946794
TI - Long-term survivors of childhood cancer: cure and care-the Erice Statement (2006)
revised after 10 years (2016).
AB - PURPOSE: The number of persons who have successfully completed treatment for a
cancer diagnosed during childhood and who have entered adulthood is increasing
over time, and former patients will become aging citizens. METHODS: Ten years
ago, an expert panel met in Erice, Italy, to produce a set of principles
concerning the cure and care of survivors of childhood and adolescent cancer. The
result was the Erice Statement (Haupt et al. Eur J Cancer 43(12):1778-80, 2007)
that was translated into nine languages. Ten years on, it was timely to review,
and possibly revise, the Erice Statement in view of the changes in paediatric
oncology and the number and results of international follow-up studies conducted
during the intervening years. RESULTS: The long-term goal of the cure and care of
a child with cancer is that he/she becomes a resilient and autonomous adult with
optimal health-related quality of life, accepted in society at the same level as
his/her age peers. "Cure" refers to cure from the original cancer, regardless of
any potential for, or presence of, remaining disabilities or side effects of
treatment. The care of a child with cancer should include complete and honest
information for parents and the child. CONCLUSIONS AND IMPLICATION FOR CANCER
SURVIVORS: Some members of the previous expert panel, as well as new invited
experts, met again in Erice to review the Erice Statement, producing a revised
version including update and integration of each of the ten points. In addition,
a declaration has been prepared, by the Childhood Cancer International Survivors
Network in Dublin on October 2016 (see Annex 1).
PMID- 29946795
TI - Characterization of soil contamination by lead around a former battery factory by
applying an analytical hybrid method.
AB - Former battery factories have created environmental and health problems for years
and the exposure to lead in surface soils has been underestimated. Nonetheless,
the identification of lead contamination and its spatial distribution is crucial.
The determination of heavy metals in soils can be performed using inductively
coupled plasma mass spectrometry (ICP-MS). However, alternative techniques such
as X-ray fluorescence (XRF) have been used lately in environmental studies since
measurements can be taken in the field in a prompt manner, despite its lower
accuracy. In this study, a former battery factory site in Monterrey, Mexico, has
been studied in order to detect lead contamination. Soil samples were assessed
for contamination by using an analytical hybrid method that comprises both
analytical techniques, namely, ICP-MS and XRF. Samples were taken in 215
locations and, after a simple homogenization process, they were analyzed by using
a portable XRF device. Within those 215 sampling points, 25 samples were analyzed
concurrently by using ICP-MS according to international sampling guidelines.
Results obtained were adjusted in order to define an analytical hybrid method,
which encompasses the advantages of each technique. An improved characterization
was achieved by using the proposed analytical hybrid method since maps of lead
distribution and calculated areas of concern showed better predictability. The
combination of spectroscopic techniques is of great applicability for
environmental agencies and decision makers.
PMID- 29946797
TI - Monitoring of Hematologic, Cardiac, and Hepatic Function in Post-Menopausal Women
with HR+/HER2- Metastatic Breast Cancer.
AB - INTRODUCTION: In the treatment of metastatic breast cancer (mBC), regular
monitoring is key in helping physicians to make informed clinical decisions,
managing treatment side effects, and maintaining patients' quality of life.
Therefore, we investigated the monitoring frequency in post-menopausal women with
HR+/HER2- mBC stratified by first-line regimen. METHODS: Treatment monitoring was
assessed using two complementary data sources: a medical chart review (chart
review analysis) and a commercial claims database (claims analysis). Women with
post-menopausal HR+/HER2- mBC who initiated first-line therapy for mBC were
selected and classified under three cohorts, based on treatment received: cyclin
dependent kinase 4/6 (CDK4/6) inhibitor (i.e., palbociclib-the only CDK4/6
approved at the time of the study), endocrine therapy (ET), and chemotherapy.
Frequency of monitoring [complete blood count (CBC), electrocardiogram (EKG), and
liver function test (LFT)] and laboratory abnormalities detected during the first
line of therapy were analyzed. RESULTS: In the chart review analysis, 64 US
oncologists abstracted medical information on 401 eligible patients, including
210 CDK4/6 users, 121 ET users, 51 chemotherapy users; 19 patients used other
regimens. All patients had >= 1 CBC; between 8.3% (ET users) and 39.5% (CDK4/6
users) had >= 1 EKG; and over 98% of patients had >= 1 LFT across all three
cohorts. Among monitored patients, 64.6% had a CBC abnormality, with anemia
(39.9%), leukopenia (27.4%), and neutropenia (26.7%) being the most common.
Abnormal EKG readings were detected in 8.4, 0.0%, and 7.7% of CDK4/6, ET, and
chemotherapy users, respectively. LFT abnormalities were detected in 14.1-26.0%
of CDK4/6 and chemotherapy users, respectively. Similar frequency of monitoring
was observed in the claims analysis, with the exception of EKG monitoring, for
which the proportion of patients tested was higher. CONCLUSION: Post-menopausal
women with HR+/HER2- mBC receiving first-line therapy with CDK4/6, ET, or
chemotherapy were regularly monitored regardless of the first-line regimen
received. FUNDING: Novartis Pharmaceuticals Corporation.
PMID- 29946796
TI - Fibro/chondrogenic differentiation of dental stem cells into chitosan/alginate
scaffolds towards temporomandibular joint disc regeneration.
AB - Tissue engineering (TE) may provide effective alternative treatment for
challenging temporomandibular joint (TMJ) pathologies associated with disc
malpositioning or degeneration and leading to severe masticatory dysfunction. Aim
of this study was to evaluate the potential of chitosan/alginate (Ch/Alg)
scaffolds to promote fibro/chondrogenic differentiation of dental pulp stem cells
(DPSCs) and production of fibrocartilage tissue, serving as a replacement of the
natural TMJ disc. Ch/Alg scaffolds were fabricated by crosslinking with CaCl2
combined or not with glutaraldehyde, resulting in two scaffold types that were
physicochemically characterized, seeded with DPSCs or human nucleus pulposus
cells (hNPCs) used as control and evaluated for cell attachment, viability, and
proliferation. The DPSCs/scaffold constructs were incubated for up to 8 weeks and
assessed for extracellular matrix production by means of histology,
immunofluorescence, and thermomechanical analysis. Both Ch/Alg scaffold types
with a mass ratio of 1:1 presented a gel-like structure with interconnected
pores. Scaffolds supported cell adhesion and long-term viability/proliferation of
DPSCs and hNPCs. DPSCs cultured into Ch/Alg scaffolds demonstrated a significant
increase of gene expression of fibrocartilaginous markers (COLI, COL X, SOX9,
COM, ACAN) after up to 3 weeks in culture. Dynamic thermomechanical analysis
revealed that scaffolds loaded with DPSCs significantly increased storage modulus
and elastic response compared to cell-free scaffolds, obtaining values similar to
those of native TMJ disc. Histological data and immunochemical staining for
aggrecan after 4 to 8 weeks indicated that the scaffolds support abundant
fibrocartilaginous tissue formation, thus providing a promising strategy for TMJ
disc TE-based replacement.
PMID- 29946799
TI - Better Understanding and Recognition of the Disconnects, Experiences, and Needs
of Patients with Irritable Bowel Syndrome with Constipation (BURDEN IBS-C) Study:
Results of an Online Questionnaire.
AB - INTRODUCTION: The BURDEN IBS-C study was conducted to better understand the
experiences, attitudes, and unmet needs of sufferers of irritable bowel syndrome
with constipation (IBS-C) in comparison to the perceptions and challenges of
healthcare providers (HCPs) who treat IBS-C patients. METHODS: This was an author
developed, online questionnaire using KnowledgePanel(r) to survey individuals
with IBS-C (N = 1311). HCPs participated in a complementary online questionnaire
and were recruited separately (N = 331). The study was fielded from June 29,
2016, to January 30, 2017. RESULTS: Most patients had used (86%) and/or were
using (76%) over-the-counter treatments for their IBS-C, with 12% currently on
prescription therapy. At the time this study was conducted, 66% and 63% were not
satisfied/completely satisfied with over-the-counter or prescription treatment,
respectively, citing inadequate efficacy (55%) and side effects (39%), most
commonly diarrhea, as common reasons for dissatisfaction. IBS-C respondents most
commonly reported feeling frustrated (43%) and stressed (28%) regarding IBS-C,
though 39% were accepting of IBS-C as part of daily life. HCPs were aligned with
patients in thinking that patients were frustrated (76%) and stressed (65%) but
HCPs were less likely to recognize that patients had become accepting of their
IBS-C (13%). Most HCPs (79%) were not satisfied/completely satisfied with the
prescription treatments available at the time this study was conducted.
Inadequate response rates to current therapies (55%) and treatment
adherence/compliance issues (58%) were the most frequent challenges encountered
by HCPs. IBS-C respondents reported that their symptoms impacted productivity and
personal activity, on average, 4 and 3 days/month, respectively. CONCLUSION:
These results suggest that current management pathways may not be adequately
addressing the symptoms and needs of individuals with IBS-C, most notably side
effects and lack of efficacy. Patients and HCPs expressed dissatisfaction with
over-the-counter and prescription treatments available at the time this study was
conducted. Additional treatment options and improved dialogue would be beneficial
to HCPs and patients. FUNDING: Synergy Pharmaceuticals Inc.
PMID- 29946798
TI - Patterns of Bicalutamide Use in Prostate Cancer Treatment: A U.S. Real-World
Analysis Using the SEER-Medicare Database.
AB - INTRODUCTION: Bicalutamide (BIC), a non-steroidal anti-androgen, is FDA-indicated
for use in combination with a luteinizing hormone-releasing hormone (LHRH) analog
for treatment of Stage D2 metastatic carcinoma of the prostate. Lack of consensus
exists regarding the clinical benefit of BIC use, either alone or combined use of
BIC with an LHRH analog or antagonist (combined androgen blockade or CAB), versus
treatment with androgen deprivation therapy (ADT) alone. METHODS: The SEER
Medicare database was used to identify prostate cancer patients aged >= 66 years
diagnosed between 2007 and 2011 and who filled at least one prescription for BIC.
Duration of BIC treatment was assessed in relation to ADT use; either alone
(monotherapy), as part of CAB only, and as part of CAB followed by monotherapy.
Additionally, we assessed use of BIC during or outside a potential testosterone
flare prevention period (initiation within 2 months of an LHRH agonist). RESULTS:
A total of 7521 prostate cancer patients who filled a prescription for BIC were
identified. Eighteen percent of the cohort used BIC alone, over half the patients
(54%) used BIC as part of CAB and 27% used BIC as part of CAB followed by
monotherapy. Among men treated with BIC as part of CAB, 58% received BIC only
within the potential flare period. CONCLUSIONS: Although there is no FDA
indication for BIC use as monotherapy, > 44% of patients in this study used BIC
alone or as part of CAB followed by monotherapy. Further research is necessary to
understand the outcomes of BIC utilization in these settings, particularly
compared with newer second-generation anti-androgens. FUNDING: Medivation LLC, a
Pfizer company, and Astellas, Pharma, Inc.
PMID- 29946800
TI - Antithyroid drug treatment for Graves' disease: baseline predictive models of
relapse after treatment for a patient-tailored management.
AB - BACKGROUND: Antithyroid drugs (ATDs) are first-line treatment for Graves'
hyperthyroidism worldwide, but relapses are frequent. The reliability of
individual risk factors to predict at baseline subsequent relapse is poor.
Predictive scores grouping single risk factors might help to select the best
treatment (pharmacological vs. ablative). OBJECTIVE: To assess the predictivity
of a recently developed score (Clinical Severity Score, CSS) and to compare it
with another score (GREAT score). PATIENTS: A retrospective observational, single
center study was conducted of 387 consecutive, newly diagnosed Graves' patients,
who completed an 18-24 months ATD course and were followed for at least 2 years.
RESULTS: Hyperthyroidism relapsed in 185 patients (48%). At diagnosis and before
treatment, the relapse group had higher serum TSH-receptor antibody and free
thyroxine levels and larger goiters than the remission group, with no differences
in Graves' orbitopathy prevalence and severity. In the multivariate analyses,
only large goiter size was significantly associated with an increased recurrence
hazard ratio. Using CSS, the risk of relapse increased from 36% in the mild
category and 49% in the moderate category to 59% in the severe category, with
quite a good area under the curve (AUC) (0.60; 95% CI: 0.55; 0.66). GREAT score
showed an increase in relapse from 34% for class I (mild) and 49% for class II
(moderate) to 64% for class III (severe) (AUC, 0.63; CI: 0.58; 0.68).
CONCLUSIONS: Both CSS and GREAT score are useful, although imperfect, tools to
predict at baseline relapse of hyperthyroidism after treatment. In real life they
may help the clinician to tailor a treatment for newly diagnosed Graves'
hyperthyroidism.
PMID- 29946802
TI - Should contrast CT urography replace non-contrast CT as an investigation for
ureteric colic in the emergency department in those aged 65 and over?
AB - PURPOSE: Elderly patients with upper tract urothelial cancer (UTUC) may present
with colic and microscopic haematuria, mimicking urolithiasis. Patients
presenting to emergency departments with acute ureteric colic are investigated
with a CT KUB. CT urography (CTU) identifies UTUC better than a CT KUB. Thus,
there is a possibility that a CT KUB may miss UTUC. METHODS: We studied patients
aged 65 years or over presenting to the emergency department with ureteric colic
and microscopic haematuria who had a CT KUB between January 2014 and October
2016. Patients who had both CT KUB and CTU were then compared to determine if CT
KUB had missed a UTUC and if the diagnoses were concordant by the two tests. A
radiologist independent from the reporting radiologists reviewed images as well
as their reports. According to the Health Research Authority, England
regulations, we did not obtain an ethical review on a voluntary basis for this
retrospective study. RESULTS: Four hundred eighty-five patients [228 (47.01%)
male and 257 (52.99%) female] had a CT KUB scan over the 34-month period. Their
mean age was 74 (SD 6.97) [males 73 (SD 6.42), females 75 (SD 7.42)] years. One
hundred eighty-seven scans were normal. Ureteric calculi (167), renal calculi
(58) and renal cysts (28) were most frequent diagnoses. The diagnosis was
uncertain in 33 patients (6.8%) [16 (48.49%) males and 17 (51.51%) females]. The
mean age of this group of patients was 74 (SD 6.64) [males 73 (SD4.43), females
74 (SD7.64)] years. These patients had a CTU for clarity. CTU identified one UTUC
not identified by CT KUB (0.2%), corroborated the diagnosis of a ureteric tumour
in one patient and excluded UTUC in two others. CTU diagnosed two new bladder
tumours and an endometrial tumour. Diagnoses were concordant between CT KUB and
CTU in 17 of 33 patients (51.5%). CONCLUSIONS: CT KUB scans for patients 65 years
and over presenting with ureteric colic is justified. Only a small proportion of
patients will subsequently require the higher radiation dose CTU as the
probability of missing UTUC is low.
PMID- 29946801
TI - Genome-scale metabolic model analysis indicates low energy production efficiency
in marine ammonia-oxidizing archaea.
AB - Marine ammonia-oxidizing archaea (AOA) play an important role in the global
nitrogen cycle by obtaining energy for biomass production from CO2 via oxidation
of ammonium. The isolation of Candidatus "Nitrosopumilus maritimus" strain SCM1,
which represents the globally distributed AOA in the ocean, provided an
opportunity for uncovering the contributions of those AOA to carbon and nitrogen
cycles in ocean. Although several ammonia oxidation pathways have been proposed
for SCM1, little is known about its ATP production efficiency. Here, based on the
published genome of Nitrosopumilus maritimus SCM1, a genome-scale metabolic model
named NmrFL413 was reconstructed. Based on the model NmrFL413, the estimated
ATP/NH4+ yield (0.149-0.276 ATP/NH4+) is tenfold lower than the calculated
theoretical yield of the proposed ammonia oxidation pathways in marine AOA (1.5
1.75 ATP/NH4+), indicating a low energy production efficiency of SCM1. Our model
also suggested the minor contribution of marine AOA to carbon cycle comparing
with their significant contribution to nitrogen cycle in the ocean.
PMID- 29946803
TI - Integrated metabolite profiling and transcriptome analysis reveals a dynamic
metabolic exchange between pollen tubes and the style during fertilization of
Brassica napus.
AB - KEY MESSAGE: In this study, we analyzed the transcriptome and metabolite profile
of the style to explore the essential metabolites and specific genes for pollen
tube growth of B. napus in vivo. For sexual reproduction of flowering plants,
pollen must germinate on the stigma and the pollen tube must grow through the
style to deliver the sperm nuclei to the female gametophyte cells. During this
process, the rapidly growing pollen tube can cover substantial distances. Despite
the clear requirements for energy and cellular building blocks in this process,
few studies have examined the role of metabolism in the style for pollen tube
elongation. In this study, we comprehensively analyzed the transcriptome and
metabolite profiles during pollen germination and pollen tube growth in the style
in Brassica napus. We profiled the transcripts and metabolites stored in pollen
and identified many transcripts related to metabolic pathways. Mature pollen
contained low levels of nutrients, whereas the styles contained high levels of
diverse nutrients. The levels of most nutrients in the style, especially
metabolites for cell wall synthesis and energy metabolism, rapidly decreased at 2
h after pollination, along with pollen germination and pollen tube elongation
through the style. A subset of genes involved in cell wall synthesis and nutrient
transport were expressed specifically in styles at 1 h after pollination. These
results demonstrated that successful fertilization involves the transcripts and
nutrients stored in mature pollen, and specific gene expression and stored
nutrients in the style. Therefore, these findings enhance our understanding of
fertilization in B. napus.
PMID- 29946804
TI - Correction to: OsbZIP71, a bZIP transcription factor, confers salinity and
drought tolerance in rice.
AB - Due to an error in combining the figure, an incorrect version of Fig. 9e was
presented in the original publication.
PMID- 29946807
TI - Correction: Number of Psychosocial Strengths Predicts Reduced HIV Sexual Risk
Behaviors Above and Beyond Syndemic Problems Among Gay and Bisexual Men.
AB - The original version of this article unfortunately contained a mistake. In the
section, "Data Collection Procedure", the last sentence was incorrect.
PMID- 29946806
TI - Multimodal treatment in locally advanced gastric cancer.
AB - According to the data of the GLOBOCAN-network of the World Health Organization,
there were 952,000 (6.8% of the total) new cases of gastric cancer in 2012,
making it the fifth most common malignancy in the world. It represents a
substantive change since the very first estimates in 1975 when stomach cancer was
the most common neoplasm. More than 70% of cases (677,000 cases) occur in
developing countries, and half the world total occurs in Eastern Asia, mainly in
China. Gastric cancer is the third leading cause of cancer death in both sexes
worldwide (Globocan, Estimated cancer incidence, mortality and prevalence
worldwide in 2012, http://globocan.iarc.fr , 2012). Annually, worldwide 723,000
patients die of this tumor entity. Interestingly, a strong change in incidence
rates in relation to the anatomical-topographic localization of the primary
tumors in the stomach and esophagus has been experienced. While the frequency of
proximal gastric carcinoma and adenocarcinoma of the cardiac and subcardiac
region in Europe and North America has been constantly rising, distal gastric
carcinomas have become less common (Torre et al. in JAMA 65:87-108, 2015).
Furthermore, the relative incidence of esophageal adenocarcinoma (mostly
localized in the distal esophagus) has strongly increased (Jemal et al. in JAMA
58:71-96, 2008; Crew and Neugut 31:450-464, 2004; Pohl and Welch 97:142-146,
2005).
PMID- 29946805
TI - Response of vascular mesenchymal stem/progenitor cells to hyperlipidemia.
AB - Hyperlipidemia is a risk factor for atherosclerosis that is characterized by
lipid accumulation, inflammatory cell infiltration, and smooth muscle cell
proliferation. It is well known that hyperlipidemia is a stimulator for
endothelial dysfunction and smooth muscle cell migration during vascular disease
development. Recently, it was found that vessel wall contains a variable number
of mesenchymal stem cells (MSCs) that are quiescent in physiological conditions,
but can be activated by a variety of stimuli, e.g., increased lipid level or
hyperlipidemia. Vascular MSCs displayed characteristics of stem cells which can
differentiate into several types of cells, e.g., smooth muscle cells, adipocytic,
chondrocytic, and osteocytic lineages. In vitro, lipid loading can induce MSC
migration and chemokines secretion. After MSC migration into the intima, they
play an essential role in inflammatory response and cell accumulation during the
initiation and progression of atherosclerosis. In addition, MSC transplantation
has been explored as a therapeutic approach to treat atherosclerosis in animal
models. In this review, we aim to summarize current progress in characterizing
the identity of vascular MSCs and to discuss the mechanisms involved in the
response of vascular stem/progenitor cells to lipid loading, as well as to
explore therapeutic strategies for vascular diseases and shed new light on
regenerative medicine.
PMID- 29946808
TI - Trend and Factors Associated with Condom Use Among Male Clients of Female Sex
Workers in Hong Kong: Findings of 13 Serial Behavioural Surveillance Surveys.
AB - This study investigated the trend and associated factors of condom use among male
clients of female sex workers (CFSW) in Hong Kong. A total of 25,443 males of the
general population were screened to identify 2,330 CFSW via 13 rounds of
population-based serial cross-sectional telephone surveys during 1998 through
2015. Over time, there were no significant changes in condom use with various
types of female sex partners (p ranged 0. 219-0.837) and prevalence of self
reported STI (p = 0.975) in the past 6 months. Decrease in the prevalence of non
regular sex partners (p < 0.001) and increase in perceived efficacy of condom use
for HIV prevention (p = 0.028) were observed. Perceived efficacy of condom use
for HIV prevention and self-reported STI experience were significantly associated
with condom use with various types of female sex partners in the past 6 months.
No evident improvement for condom use was found. Tailored intervention programs
are warranted.
PMID- 29946809
TI - Iatrogenic obstructive hydrocephalus resulting from Gelfoam accumulation within
the cerebral aqueduct: a case report.
AB - The authors present the case of a previously healthy 12-year-old male with
intractable seizures localized to a right frontal area of encephalomalacia and
porencephalic cyst who underwent resection of the seizure focus. The surgical
resection cavity extended into the right lateral ventricle, and due to
encountered hemorrhage, Gelfoam was used for optimal hemostasis. The patient did
well following the procedure, but presented 5 months later with headaches and
emesis and was discovered to have obstructive hydrocephalus on imaging studies.
Endoscopic third ventriculostomy (ETV) was performed, where Gelfoam was
encountered in the third ventricle, obstructing the cerebral aqueduct. After the
completion of the ETV, the patient did well and continues to be asymptomatic 1
year following the procedure.
PMID- 29946811
TI - Correction to: Benefit Duration and Return to Work Outcomes in Short Term
Disability Insurance Programs: Evidence from Rhode Island's Temporary Disability
Insurance Program.
AB - The original version of this article unfortunately contained a mistake in the
article title. The text "Rhode Island's" inadvertently omitted in the original
publication.
PMID- 29946810
TI - Outcomes from 18 years of cervical spine surgery in MPS IVA: a single centre's
experience.
AB - PURPOSE: This study examines the long-term outcomes of paediatric Morquio (MPS
IVA) patients undergoing cervical spine surgery and evaluates the factors that
impacting this. METHODS: A retrospective review was performed on all MPS IVA
patients undergoing cervical spine surgery, since the introduction of
standardised neuroradiological screening. The impact of preoperative neurological
status, growth, genotype and radiological status on outcome is assessed, whilst
long-term surgical, radiological and neurological outcomes are documented.
RESULTS: Twenty-six of the eighty-two MPS IVA patients (31%) reviewed underwent
cervical spine surgery at a median age of 6.1 years (range, 1.45 to 15.24).
Preoperatively, cord signal change was seen in 11 patients with 5 being
myelopathic; however, 6 clinically manifesting patients had no overt cord signal
change. Postoperatively, none of the 14 preoperatively clinically asymptomatic
patients followed long term progressed neurologically during a median follow-up
of 77.5 months (range = 18-161). Of the ten preoperatively clinically symptomatic
patients who were followed up for the same duration, seven continued to
deteriorate, two initially improved and one remained stable. Radiological follow
up performed for a median duration of 7 years (range = 0.5-16) has shown a degree
of stenosis at the level immediately caudal to the termination of the graft in
76% of patients, though only one has become clinically symptomatic and required
revision. CONCLUSIONS: Once clinically elicitable neurological signs become
evident in patients with MPS IVA, they tend to progress despite surgical
intervention. Referring clinicians should also not be falsely reassured by the
lack of T2 spinal cord signal change but should consider surgical intervention in
the face of new clinical symptomology or radiological signs of progressive canal
stenosis or instability.
PMID- 29946812
TI - Cross-Cultural Adaptation of the Work Rehabilitation Questionnaire (WORQ) to
French: A Valid and Reliable Instrument to Assess Work Functioning.
AB - Purpose The Work Rehabilitation Questionnaire (WORQ) is a patient-reported
instrument to assess work related functioning in vocational rehabilitation (VR)
and work, based on the International Classification of Functioning, Disability
and Health (ICF) core set for VR. The objective of this study was to cross
culturally adapt WORQ to French and to evaluate its psychometric properties.
Methods The cross-cultural adaptation followed a dual-panel approach.
Psychometrics was examined in one VR-centre in the French speaking part of
Switzerland. Test-retest reliability was analyzed with intraclass correlation
coefficient (ICC), internal consistency was assessed with Cronbach's alpha.
Construct validity was determined by convergence to the self-reported general
functioning scale and the Hospital Anxiety and Depression Scales (HADS). The
association of patient's return-to-work expectation within 6-months and having a
case manager was examined. The usability of WORQ-French was tested in 10 VR
patients. Results Eighty-nine patients with musculoskeletal injuries were
included. WORQ-French showed excellent internal consistency (0.968) and a high
test-retest reliability (0.935). WORQ-French was positively associated with self
reported general functioning (r = 0.662) and both HADS scales (r = 0.56-0.57).
Neither the patient's return-to-work expectation nor having a case manager were
significantly correlated with WORQ-French. Usability in terms of
understandability of questions and response options was found to be good. Seven
patients rated the length of WORQ-French as good, while two found the instrument
a little too long and one found it too long. Conclusions WORQ French is a valid,
reliable, and easy to administer instrument to assess self-reported work
functioning given our study setting and sample characteristics.
PMID- 29946813
TI - Work-Related Outcomes in Self-Employed Cancer Survivors: A European Multi-country
Study.
AB - Purpose To describe: (i) patterns of self-employment and social welfare
provisions for self-employed and salaried workers in several European countries;
(ii) work-related outcomes after cancer in self-employed people and to compare
these with the work-related outcomes of salaried survivors within each sample;
and (iii) work-related outcomes for self-employed cancer survivors across
countries. Methods Data from 11 samples from seven European countries were
included. All samples had cross-sectional survey data on work outcomes in self
employed and salaried cancer survivors who were working at time of diagnosis (n =
22-261 self-employed/101-1871 salaried). The samples included different cancers
and assessed different outcomes at different times post-diagnosis. Results Fewer
self-employed cancer survivors took time off work due to cancer compared to
salaried survivors. More self-employed than salaried survivors worked post
diagnosis in almost all countries. Among those working at the time of survey,
self-employed survivors had made a larger reduction in working hours compared to
pre-diagnosis, but they still worked more hours per week post-diagnosis than
salaried survivors. The self-employed had received less financial compensation
when absent from work post-cancer, and more self-employed, than salaried,
survivors reported a negative financial change due to the cancer. There were
differences between self-employed and salaried survivors in physical job demands,
work ability and quality-of-life but the direction and magnitude of the
differences differed across countries. Conclusion Despite sample differences,
self-employed survivors more often continued working during treatment and had, in
general, worse financial outcomes than salaried cancer survivors. Other work
related outcomes differed in different directions across countries.
PMID- 29946814
TI - Correction to: Functional Capacity Evaluation in Different Societal Contexts:
Results of a Multicountry Study.
AB - The original version of this article unfortunately contained a mistake in the
Table 2. The data under column head "Left handgrip strength (n = 336)" was
erroneously omitted during the production process. The corrected Table 2 is given
below.
PMID- 29946815
TI - Protein-templated Fe2O3 microspheres for highly sensitive amperometric detection
of dopamine.
AB - The authors describe an amperometric sensor for dopamine (DA) by employing olive
like Fe2O3 microspheres (OFMs) as the electrocatalyst for DA oxidization. The
OFMs were prepared by using a protein templated method. The structure and
properties of the OFMs were characterized by scanning electron microscopy, X-ray
powder diffraction, energy dispersive x-ray spectroscopy, cyclic voltammetry and
electrochemical impedance spectroscopy. The OFMs possess excellent catalytic
activity towards DA oxidization due to their unique morphology. The sensor
responds to DA within less than 5 s. The sensor, best operated at a voltage of
+0.2 V (vs. SCE) responds linearly in the 0.2 to 115 MUM DA concentration range
and has a 30 nM detection limit. The selectivity, reproducibility and long-term
stability of the sensor are acceptable. It performs well when applied to spiked
human urine samples. Graphical abstract Olive-like Fe2O3 microspheres (OFMs),
synthesized using egg white as template, display excellent catalytic activity
towards dopamine (DA) oxidization due to their unique morphology. They were
applied for DA detection using the amperometric technique. The electrochemical
sensor exhibited a high sensitivity and a 30 nM detection limit. DAQ:
dopaquinone.
PMID- 29946816
TI - HbA1c levels at 90 days after renal transplantation in non-diabetic recipients
predict de novo pre-diabetes and diabetes at 1 and 3 years after transplantation.
AB - PURPOSE: Pre-diabetes, a risk factor for post-transplant diabetes mellitus
(PTDM), represents an early therapeutic target for prevention of PTDM. We
evaluated glucose metabolism post-transplantation and the ability to predict pre
diabetes and PTDM from haemoglobin A1c (HbA1c) levels at 90 days, at 1 year, and
at 3 years in long-term post-transplantation follow-up. METHODS: HbA1c levels
were measured in 71 non-diabetic deceased-donor transplant recipients at four
time points (during transplantation, 90-days post-transplantation, 1-year post
transplantion, and at the final post-transplantation follow-up visit 2.71 +/-
1.26 years after transplantation). The predictive power of HbA1c levels at 90
days post-transplantation was determined by calculating the sensitivity,
specificity, false-positive rates, and false-negative rates. A multivariate
logistic regression analysis was performed to determine risk factors for pre
diabetes and PTDM at 1-year post-transplantation and at the last follow-up visit
(2.71 +/- 1.26 years after renal transplantation). RESULTS: HbA1c values >= 5.7%
were seen in 79% of patients at 90 days post-transplant, in 83% at 1 year, and in
69% of patients on follow-up. HbA1c cut-off levels of < 5.7% or >= 5.7% showed
the highest predictive sensitivity for pathological HbA1c levels (>= 5.7%) at 1
year post-transplantation (0.83) and at last follow-up (0.86), whereas cut-off
levels of < 6.2% or .>= 6.2% showed the highest specificity (0.97 and 1.00,
respectively). The HbA1c level at 90 days was a risk factor for disturbed glucose
metabolism at 1 year (p = 0.000) and at the final follow-up (p = 0.031).
CONCLUSION: HbA1c levels at 90 days post-transplantation are predictive of
disturbed glucose metabolism at 1 year and on long-term follow-up and may serve
as predictive tools for early therapeutic interventions to prevent PTDM.
PMID- 29946817
TI - Serum bilirubin level and its impact on the progression of chronic kidney
disease.
AB - PURPOSE: To examine whether an elevated serum total bilirubin level affects the
decline in renal function or new-onset chronic kidney disease (CKD) in patients
with type 2 diabetes mellitus (DM2). METHODS: This was a longitudinal
observational study in patients who presented at the University of Health
Sciences Hospital in Kayseri. Five hundred twenty-nine patients with DM2 who had
conserved renal function were enrolled (estimated glomerular filtration rate > 60
ml/min/1.73 m2). Arising CKD stage 3 was the outcome measure. The patients were
separated into three groups based on the total serum bilirubin levels. The first
group (G1) ranged from 0.1 to 0.3, the second (G2) 0.4-0.5, and the third (G3)
0.6-0.9 mg/dl. The effect of total serum bilirubin levels on CKD 3 development
was assessed using Cox proportional hazards regression. RESULTS: The risk of the
CKD stage 3 development was highest in G1 who has the lowest serum total
bilirubin levels (G1 vs. G3; hazard ratio [HR], 2.02; 95% confidence interval
[CI] 1.21-3.36; p = 0.007). In addition, G2 had a significant risk of CKD stage 3
development (G2 vs. G3; hazard ratio [HR], 1.58; 95% confidence interval [CI]
1.08-2.32; p = 0.018). In the adjusted analysis, compared to G2 and G3, G1 had
the highest risk (G1 vs. G3; hazard ratio [HR], 2.20; 95% confidence interval
[CI] 1.29-3.77; p = 0.004). Similarly, G2 had a higher risk compared to G3
(hazard ratio [HR], 1.57; 95% confidence interval [CI] 1.05-2.34; p = 0.028).
CONCLUSIONS: Serum bilirubin may predict the progression of CKD in patients with
type 2 diabetes and preserved kidney function.
PMID- 29946818
TI - Effect of frequency of intravenous iron administration on hemoglobin variability
in maintenance hemodialysis patients.
AB - TARGET: To observe the effect on hemoglobin (Hb) variability with different
treatment frequencies of intravenous iron in maintenance hemodialysis (MHD)
patients. METHODS: There were 41 MHD patients enrolled in the cohort. The
patients were separated into two groups randomly. The baseline data were
collected after oral iron agents for 1 month (wash out). There were two methods
of intravenous iron administration, either continuous or intermittent. For
continuous administration (CA), 100 mg sucrose iron agents were given during
every HD session with total dose of 1000 mg. For intermittent administration
(IA), 100 mg sucrose iron agents were given once every week with the same total
dose of 1000 mg. The protocol were designed to do a follow-up of 7 months, which
included two to three-month steps of different administrations of intravenous
iron and 1 month of wash-out period by oral iron agents between two steps,
respectively. Patients in Group one (G1) administrated iron agents by CA at the
first step and IA at the second step. Patients in Group two (G2) did IA and then
transfer to CA. The clinical parameters including Hb, serum ferritin (SF),
transferrin saturation (TAST), and doses of recombined human erythropoietin
(rHuEPO) were detected and recorded during follow-up period. The standard
deviation of Hb (Hb-SD) and coefficient variation of Hb (Hb-CV) were calculated.
The baseline data were compared between two groups. The parameters on month 3 and
7 were compared with those on month 0 in two groups, respectively. The effects of
both CA and IA on Hb-SD and Hb-CV were compared by two-stage cross-comparison
general linear model (GLM) method. RESULTS: There were 34 patients (82.9%)
completed the trail. The amounts of cases, rates of gender and primary diseases,
the mean value of age, Hb, SF, TSAT, and doses of rHuEPO on baseline in two
groups were similar (p > 0.05). The SF levels in two groups increased
significantly during follow-up period, which were 235.4 +/- 51.8 ng/ml on month
0, 362.4 +/- 140.2 ng/ml on month 3, and 315.0 +/- 97.73 ng/ml on month 7 in G1
(p < 0.01), and 250.5 +/- 37.8 ng/ml, 332.2 +/- 118.9 ng/ml, and 347.4 +/- 124.3
ng/ml in G2 (p < 0.01), respectively. Compared to CA, IA could decline the Hb-SD
(5.93 +/- 3.97 g/l vs. 7.36 +/- 3.81 g/l, F = 4.377, p = 0.044) and Hb-CV (0.054
+/- 0.035 vs. 0.069 +/- 0.030, F = 7.042, p = 0.012) significantly. The mean
levels of Hb and doses of rHuEPO were similar between CA and IA. CONCLUSION: The
administration of intravenous iron by CA or IA has the similar effects on iron
supplement and anemia treatment. However, IA may be more benefit to Hb
variability than CA in MHD patients.
PMID- 29946819
TI - Case report of an ewing's sarcoma/primitive neuroectodermal tumor of the kidney.
PMID- 29946820
TI - Intra-thoracic placement of central venous catheter despite ultrasound guidance.
PMID- 29946821
TI - TLR4 and RAGE conversely mediate pro-inflammatory S100A8/9-mediated inhibition of
proliferation-linked signaling in myeloproliferative neoplasms.
AB - PURPOSE: Previously, the family of S100A proteins has been found to be associated
with inflammation and myelopoiesis and to be able to induce or support
myeloproliferation during chronic inflammation. Here, we studied the inflammatory
myeloid-related proteins S100A4, S100A8, S100A9 and S100A12 in myeloproliferative
neoplasms (MPNs) in order to assess the involvement of chronic inflammation in
the pathogenesis of MPN. METHODS: We analyzed the S100A4, S100A8, S100A9 and
S100A12 mRNA and protein levels in the bone marrow and circulation of 140
patients with MPN and 15 healthy controls using Western blotting, microarray
based mRNA expression profiling and ELISA assays, respectively. In addition we
performed functional studies on the proliferation-related AKT and ERK1/2
signaling pathways in MPN-derived granulocytes using Western blotting and
proteomic analyses. RESULTS: We found that the S100A mRNA levels were increased
in MPN patient-derived circulatory CD34+ cells, and that their protein expression
levels were also augmented in their granulocytes and bone marrow stroma cells,
depending on the JAK2V617F mutation allele burden. We also found that
calreticulin (CALR) mutations were related to reduced S100A8 plasma levels in
primary myelofibrosis (PMF). The S100A8 plasma levels were found to be increased
in MPN, the S100A9 plasma levels in PMF and essential thrombocythemia (ET), and
the S100A12 plasma levels in polycythemia vera (PV). These S100A plasma levels
showed a positive correlation with the systemic inflammation marker IL-8, as well
as with the numbers of leukocytes and thrombocytes, depending on the JAK2V617F
mutation status. Additionally, we found that heterodimeric S100A8/9 can inhibit
the AKT pathway in MPN-derived granulocytes mediated by the Toll-like receptor 4
(TLR4), depending on the CALR mutation status. Conversely, we found that blocking
of the receptor for advanced glycation end products (RAGE) increased the S100A8/9
mediated inhibition of AKT signaling in the MPN-derived granulocytes. Moreover,
we found that heterodimeric S100A8/9 generally induced TLR4-mediated ERK1/2
dephosphorylation proportionally to the JAK2V617F mutation allele burden.
TLR4/RAGE blocking prevented the S100A8/9-mediated inhibition of ERK1/2
phosphorylation in PV. CONCLUSIONS: From our data we conclude that the S100A8 and
S100A9 granulocyte and plasma levels are increased in MPN patients, along with
inflammation markers, depending on their JAK2V617F mutation allele burden. We
also found that S100A8/9-mediated inhibition of the proliferation-related AKT and
ERK1/2 signaling pathways can be decreased by CALR mutation-dependent TLR4
blocking and increased by RAGE inhibition in MPN.
PMID- 29946823
TI - Cardiac amyloidosis: A new challenge of multimodality imaging.
PMID- 29946822
TI - Training state and fasting-induced PDH regulation in human skeletal muscle.
AB - The aim of the present study was to examine the influence of training state on
fasting-induced skeletal muscle pyruvate dehydrogenase (PDH) regulation,
including PDH phosphorylation. Trained and untrained subjects, matched for
skeletal muscle CS activity and OXPHOS protein, fasted for 36 h after receiving a
standardized meal. Respiratory exchange ratio (RER) was measured and blood as
well as vastus lateralis muscle biopsies were obtained 2, 12, 24, and 36 h after
the meal. RER decreased with fasting only in untrained individuals, while PDHa
activity decreased from 12 h after the meal in untrained, but only tended to
decrease at 36 h in trained. PDH-E1alpha, PDP1 protein, PDH phosphorylation, and
PDH acetylation in skeletal muscle was higher in trained than untrained subjects,
but did not change with fasting, while PDK4 protein was higher at 36 h than at 2
h after the meal in both groups. In conclusion, the present results suggest that
endurance exercise training modifies the fasting-induced regulation of PDHa
activity in skeletal muscle and the substrate switch towards fat oxidation. PDH
phosphorylation could not explain the fasting-induced regulation of PDHa activity
suggesting other post translational modifications.
PMID- 29946824
TI - Automatic calculation of myocardial external efficiency using a single 11C
acetate PET scan.
AB - BACKGROUND: Myocardial external efficiency (MEE) is defined as the ratio of
kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean
systemic pressure] and the chemical energy from oxygen consumed (MVO2) by the
left ventricular mass (LVM). We developed a fully automated method for estimating
MEE based on a single 11C-acetate PET scan without ECG-gating. METHODS AND
RESULTS: Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and
20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center
study. MVO2 was calculated using washout of 11C -acetate activity. FCO and LVM
were calculated automatically using dynamic PET and parametric image formation.
FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all
subjects. The correlation between MEEPET-CMR and MEEPET was high (r = 0.85, P <
0.001) without significant bias. MEEPET was 23.6 +/- 4.2% for controls and was
lowered in AVS (17.2 +/- 4.3%, P < 0.001) and in MVR (18.0 +/- 5.2%, P = 0.004).
MEEPET was strongly associated with both NYHA class (P < 0.001) and the magnitude
of valvular dysfunction (mean aortic gradient: P < 0.001, regurgitant fraction: P
= 0.009). CONCLUSION: A single 11C-acetate PET yields accurate and automated MEE
results on different scanners. MEE might provide an unbiased measurement of the
phenotypic response to valvular disease.
PMID- 29946825
TI - Relationship of 82Rb PET territorial myocardial asynchrony to arterial stenosis.
AB - OBJECTIVE: 82Rb PET/CT rest/regadenoson-stress data enable quantification of left
ventricular rest and stress function, perfusion, and asynchrony. Our study was
conducted to determine which parameters best identify patients with multi-vessel
disease (MVD) and individual stenosed arteries. METHODS: PET/CT data were
reviewed retrospectively for 105 patients referred for evaluation of CAD, who
also underwent angiography. % arterial stenosis was determined quantitatively at
a core laboratory. Severe stenosis was defined as >= 70%, and MVD as 2 or more
stenosed arteries. Segmental MBF was calculated from first-pass data for arterial
territories. Regional rest and stress systolic and diastolic asynchrony (Asynch)
scores were determined from visual examination of phase polar maps. RESULTS: 65
vessels had stenoses >= 70%. 15 patients had MVD. ROC area under curve (ROC AUC)
for identifying patients with MVD was 83% for Asynch and 73% for MFR. ROC AUC for
identifying individual arterial territories with stenoses >= 70% was 81% and 72%
for Asynch and MFR. CONCLUSION: 82Rb PET/CT accurately identified patients with
MVD and individual stenosed territories, with regional asynchrony measurements
contributing significantly to identify patients with CAD.
PMID- 29946826
TI - Suboptimal performance of cardiovascular magnetic resonance imaging for the
assessment of myocardial viability at the early phase of an acute coronary
syndrome: Usefulness of SPECT myocardial perfusion imaging.
PMID- 29946827
TI - Accessory nerve distribution for aesthetic botulinum toxin injections into the
upper trapezius muscle: anatomical study and clinical trial : Reproducible BoNT
injection sites for upper trapezius.
AB - PURPOSE: The descending part of the trapezius muscle is clinically associated
with neck pain and aesthetic applications. The innervation of the trapezius
muscle is not well described in the medical literature for clinicians. The aim of
study was to analyze the perforating branch pattern of the accessory nerve in the
descending part of the trapezius muscle with the aim of describing the most
efficient and reproducible BoNT injection sites for aesthetic treatment of
shoulder contouring. METHODS: Twenty-six specimens (five male and eight female)
from embalmed Korean cadavers were used in this study. The trapezius muscle was
dissected scrupulously and then reflected to enable examination of the locations
of the perforating points. The thickness of trapezius muscle was measured in 13
volunteers using a diagnostic ultrasonography system. BoNT was injected into the
trapezius muscle bilaterally. Injections were performed at 6 points separated by
2 cm. The muscle thicknesses were measured three times using ultrasonography:
before the injection and at 4 and 12 weeks after the injection. RESULTS: The
dense arborization of the perforating accessory nerve branches was confined
mostly to section b (66.7%, 54/81) and section c (33.3%, 27/81). The mean muscle
thickness at 4 and 12 weeks consistently decreased 0.68-0.63 cm in conventional
method and 0.65-0.61 cm in new method (NDM) respectively (right and left).
CONCLUSION: To optimize the outcome of BoNT injection, we recommended injecting
into six points separated by 2 cm in sections b and c of the upper trapezius
muscle. It is significant that it is easier to apply to anyone than to apply
unstructured techniques.
PMID- 29946828
TI - The urinary microbiome in patients with refractory urge incontinence and
recurrent urinary tract infection.
AB - INTRODUCTION AND HYPOTHESIS: Urinary urge incontinence is a chronic, debilitating
condition that is difficult to treat. Patients refractory to standard
antimuscarinic therapy often experience recurrent urinary tract infections
(rUTIs). The microbiota of these refractory patients with rUTI remains
unexplored. METHODS: A midstream urine (MSU) sample was collected from patients
with refractory urge incontinence and coexistent rUTI during acute symptomatic
episodes. Culture-based diagnosis was performed using routine microbiological
methods. Culture-independent profiling was performed using bacterial 16S RNA
profiling. E. coli strain typing was performed by amplicon pyrosequencing of the
fimH gene. RESULTS: Over 2 years, 39 patients with refractory urge incontinence
and coexistent rUTI were studied, yielding 9 severely affected cases. These 9
patients were carefully monitored for a further 2 years, resulting in the
collection of 102 MSU samples, 70 of which were diagnosed as UTI (median of 8
UTIs/woman). Culture-independent analysis of 38 of these samples revealed the
existence of a diverse urinary microbiota. Strain typing of E. coli identified
instances of rUTI caused by the same persisting strain and by new infecting
strains. CONCLUSIONS: Patients with refractory urge incontinence and coexistent
rUTI possess a diverse urinary microbiota, suggesting that persistent bladder
colonisation might augment the pathology of their chronic condition.
PMID- 29946829
TI - Increased risk for stress urinary incontinence in women with postmenopausal
hormone therapy.
AB - INTRODUCTION AND HYPOTHESIS: The impact of estradiol-based hormone therapy (HT)
on the incidence of stress urinary incontinence (SUI) is unknown. Therefore, we
compared the use of such HT regimens and tibolone in women with and without SUI.
METHODS: The women with a history of SUI operation (N = 15,002) were identified
from the Finnish National Hospital Discharge Register, and the control women
without such an operation (N = 44,389) from the Finnish Central Population
Register. The use of HT was traced from the National Drug Reimbursement Register,
and the odd ratios (ORs) with 95% confidence intervals (95% CIs) for SUI were
calculated by using the conditional logistic regression analysis. RESULTS: The
cases had used any HT more often than the controls. The use of systemic estradiol
only or estradiol-progestin therapy was accompanied by an increased SUI risk (OR
3.8, 95% CI: 3.6-4.0 and OR 2.7, 95% CI: 2.6-2.9 respectively). The use of
estradiol with noretisterone acetate showed a higher risk of increase than that
with medroxyprogesterone acetate. Age over 55 years at the initiation of systemic
HT was accompanied by a higher SUI risk increase than that under 55 years of age.
The use of tibolone, an estradiol + levonorgestrel-releasing intrauterine device,
or vaginal estradiol also increased the risk. CONCLUSIONS: The use of HT regimens
may predispose to the de novo development or worsening of pre-existing SUI. Thus,
caution is needed when these regimens are prescribed to women with mild stress
related urine leakage or with established SUI risk factors.
PMID- 29946830
TI - Assessment of measurement methods of posterior inflammation in stromal
choroiditis: the value of quantitative outcome measures versus the presently
qualitatively based paradigm.
AB - PURPOSE: To assess posterior inflammation using a fluorescein (FA)/indocyanine
green angiography (ICGA) scoring system, and compare them to the presently
recommended outcome measure, the standardization of uveitis nomenclature vitreous
haze score (SUN-VH) in stromal choroiditis. METHODS: This was a retrospective
study on patients with a diagnosis of ocular sarcoidosis(OS), ocular
tuberculosis(OT), Birdshot retinochoroiditis(BRC) and Vogt-Koyanagi-Harada
disease(VKH) seen in the Centre for Ophthalmic Specialized Care, Lausanne,
Switzerland. Angiography signs were quantified according to an established
FA/ICGA scoring system. Vitritis was assessed using SUN-VH. Results were
compared. RESULTS: 65 newly diagnosed patients (128 eyes) with stromal
choroiditis were included. Angiographic scoring showed variable degrees of
choroidal versus retinal involvement (87% for OS, 72% for OT, 62.5% for BRC and
100% for VKH). On the other hand, a mere 22 of 128 eyes (17%) showed a SUN-VH
score >= 2 necessary for inclusion in clinical trials. Moreover, FA/ICGA values
followed a normal distribution curve and presented inter-examiner variations
greater than 1-SD in only 8.4% of cases. SUN-VH values' distribution was non
normal and showed inter-examiner discrepancies greater than 1-SD in 51.7% of
cases. CONCLUSION: This study highlights the precise measurement of global
posterior inflammation achieved by a dual FA/ICGA scoring system in stromal
choroiditis. In contrast, SUN-VH scale appears imprecise and inadequate, as only
a minute percentage of the studied eyes could have been included in a clinical
trial based on this criterion. To evaluate posterior intraocular inflammation
meaningfully in stromal choroiditis, the use of dual FA/ICGA is strongly advised
and should replace the presently recommended SUN-VH system.
PMID- 29946831
TI - Smoke aerosols dispersion and transport from the 2013 New South Wales (Australia)
bushfires.
AB - Environmental monitoring and modelling, especially in the regional context, has
seen significant progress with the widely usage of satellite measurement in
conjunction with local meteorological and air quality monitoring to understand
the atmospheric dispersion and transport of air pollutants. This paper studies
the application of these data and modelling tools to understand the environment
effects of a major bushfire period in the state of New South Wales (NSW),
Australia, in 2013. The bushfires have caused high pollution episodes at many
sites in the greater Sydney metropolitan areas. The potential long-range
transport of aerosols produced by bushfires to other region and states has been
seen by regulators as a major concern. Using data and images collected from
satellites, in addition to the results obtained from different simulations
carried out using HYSPLIT trajectory model and a regional meteorological model
called Conformal Cubic Atmospheric Model (CCAM), we were able to identify at
least 2 days on which the smoke aerosols from bush fires in NSW has been
transported at high altitude to the northern state of Queensland and the Coral
Sea. As a result, widespread high particle concentration in South East Queensland
including the Brisbane area, as measured by nearly all the air quality monitoring
stations in this region, occurred on the day when the smoke aerosols intruded to
lower altitude as indicated by the CALIOP (Cloud-Aerosol Lidar with Orthogonal
Polarization) Lidar measurements on the CALIPSO (Cloud-Aerosol Lidar and Infrared
Pathfinder Satellite Observation) satellite. The use of meteorological or air
quality modelling to connect the ground-based measurements with satellite
observations as shown in this study is useful to understand the pollutant
transport due to bushfires and its impact on regional air quality.
PMID- 29946832
TI - Screw-retained monolithic zirconia vs. cemented porcelain-fused-to-metal implant
crowns: a prospective randomized clinical trial in split-mouth design.
AB - OBJECTIVES: The objective of the present study was to compare the clinical
performance of screw-retained, monolithic, zirconia, and cemented porcelain-fused
to-metal (PFM) implant crowns. MATERIALS AND METHODS: In a prospective,
randomized, clinical, split-mouth trial, 22 patients' bilateral premolar or molar
single-gap were restored with either screw-retained (test group) or cemented
supraconstruction (control group). Clinical parameters, soft-tissue health,
crestal bone-level changes, technical complications, and patient's subjective
feelings were recorded during a follow-up period of 12 months. RESULTS: No
implant was lost during the follow-up period. Of the crowns, 4.5% (test) and 9.1%
(control) showed bleeding on probing (P = 1.000), and plaque was visible in 13.6%
(test) and 27.3% (control) of the crowns (P = 0.240). Changes in bone crest level
seemed to have no correlation with the restoration method (P = 0.77/0.79).
Technical failures were observed in three restorations of the test and four of
the control group. Evaluation of patients' satisfaction revealed high acceptance
regarding fit, esthetics, and chewing effectiveness in both groups. CONCLUSION:
Over a 12-month follow-up, screw-retained and cemented crowns could show
comparable clinical and radiological results regarding soft tissue health,
marginal bone level, and patient satisfaction. Duration of treatment alone was
significantly shorter in screw-retained crowns. CLINICAL RELEVANCE: Prosthetic
retention methods are related with the occurrence of complications, such as peri
implantitis. However, scientific valuable data that proof superiority of a
specific retention technique are rare. In single-gap implants, screw retention
and cementation seemed to achieved comparable results.
PMID- 29946833
TI - Autotrophic, Heterotrophic, and Mixotrophic Nitrogen Assimilation for Single-Cell
Protein Production by Two Hydrogen-Oxidizing Bacterial Strains.
AB - To recover a nitrogen resource from high-ammonia-nitrogen wastewater, two
amphitrophic hydrogen-oxidizing bacteria (HOB), Paracoccus denitrificans Y5 and
P. versutus D6, capable of nitrogen assimilation for single-cell protein (SCP)
production were isolated. These two HOB strains could grow autotrophically with
H2 as an electron donor, O2 as an electron acceptor, CO2 as a carbon source, and
ammonia nitrogen (NH4+-N) as a nitrogen source. The cell molecular formulas of
strains Y5 and D6 determined by autotrophic cultivation were C3.33H6.83O2.58N0.77
and C2.87H5.34O3.17N0.57, respectively. The isolated strains could synchronously
remove NH4+-N and organic carbon and produce SCP via heterotrophic cultivation.
The rates of removal of NH4+-N and soluble chemical oxygen demand reached 35.47
and 49.04%, respectively, for Y5 under mixotrophic cultivation conditions with
biogas slurry as a substrate. SCP content of strains Y5 and D6 was 67.34-73.73%
based on cell dry weight. Compared with soybean meal, the SCP of Y5 contained a
variety of amino acids.
PMID- 29946834
TI - Decoupling effect and forecasting of economic growth and energy structure under
the peak constraint of carbon emissions in China.
AB - The decoupling effect between economic growth and energy structure was
quantitatively analyzed from 1999 to 2014 across China. The results showed it
existed weak decoupling effects in most regions. Based on the analysis of the
influence of energy structure on carbon intensity, using scenario simulation
methods and Markov chain modeling, the carbon intensity was predicted for China
in 2020. The impact of energy structure adjustment on the carbon intensity to
meet China's carbon target by 18 possible scenarios are calculated. Furthermore,
the peak value of carbon emissions was also calculated in 2030. The results
showed that the carbon intensity predicted for China in 2020 can be achieved
regardless of whether the energy structure was adjusted or not when energy saving
and carbon reduction policies maintained with economic growth at 6-7%. Moreover,
given fixed energy structure growth, for each 1% of economic growth, the carbon
intensity will decrease by about 3.5%. Given fixed economic growth, the decrease
of energy intensity will be greater if the control of energy consumption is
stronger. The effect of energy structure adjustment on the decreasing of carbon
intensity will be 4% higher under constraints than without constraints. On
average, the contribution of energy structure adjustment to achieving the carbon
intensity target was calculated as 4% higher than that with constraints. In
addition, given relatively fixed economic growth at 6-7%, the peak value of
carbon emission in 2030 was calculated as 13.209 billion tons with constraints
and 14.38 billion tons without constraints.
PMID- 29946835
TI - Effect of pressure and temperature on anaerobic methanotrophic activities of a
highly enriched ANME-2a community.
AB - This study investigated the effect of temperature and methane partial pressure on
the anaerobic methane-oxidizing and sulfate-reducing (AOM-SR) activities by a
highly enriched ANME-2a community. The ANME-2a-enriched biomass was incubated at
different pressures, i.e., 2, 10, 20, and 30 MPa at 15 degrees C for 80 days.
The response of the microbial community with temperature was investigated in
incubations at 4, 15, and 25 degrees C at 10 MPa. Among all tested conditions,
the incubation at 10 MPa pressure and 15 degrees C showed the highest AOM-SR
activity of the studied ANME-2a phylotype, whereas activity at 2 MPa pressure and
15 degrees C was almost comparative to the response at 10 MPa pressure. The
finding of the most favorable conditions for AOM-SR activity by the studied AOM
SR community comparable to the in situ pressure and temperature (15 degrees C at
10 MPa) suggests that the studied ANME-2a phylotype was well adapted to the
conditions similar to its origin. The microbial community analysis showed that
the bacterial community composition shifted upon changing the incubation
temperature and pressure.
PMID- 29946837
TI - Coupling and decoupling effects of agricultural carbon emissions in China and
their driving factors.
AB - The relationship between agricultural carbon emissions and agricultural economic
growth has attracted a significant research attention. A key issue to address in
the development of agriculture is the reduction of agricultural carbon emissions
while maintaining agricultural economic growth. This study investigated the
interactions between agricultural carbon emissions and agricultural economic
growth from multiple perspectives based on agricultural carbon emission data from
30 provinces in China measured from 1997 to 2015. Using this dataset, the
coupling and decoupling effects of agricultural carbon emissions and the
underlying driving factors were explored using a coupling development degree
model, the Tapio decoupling assessment model, and a logarithmic mean Divisia
index (LMDI) decomposition model. The results were as follows: (1) at the
regional scale, the degree of coupling development between agricultural carbon
emissions and agricultural economic growth is high in the central region of China
and low in the western region. At the provincial scale, the coupling effects of
agricultural carbon emissions exhibited four levels: minimal, low, moderate, and
high coupling. (2) With the exceptions of Beijing, Zhejiang, Fujian, Guangdong,
Inner Mongolia, and Shanghai, the relationships between agricultural carbon
emissions and agricultural economic growth in the other 24 provinces were in a
weak decoupling state. (3) The effects of agricultural development scale and
agricultural technical progress were the major driving factors associated with
increases and decreases in agricultural carbon emissions, respectively.
PMID- 29946836
TI - The impact of kraft pulping effluent on egg survival and hatching success in two
species of Clupeiformes (Teleostei).
AB - The anchoveta (Engraulis ringens) and sardine (Strangomera bentincki) are coastal
pelagic species with important spawning areas off the coast of Chile. The
discharge of secondary-treated effluents from a kraft pulp plant near one of
these spawning areas has raised environmental concerns. Therefore, effluent
effects on the development of anchoveta and sardine eggs were assessed by in
vitro exposure. Eggs were sampled between 2007 and 2010 off Talcahuano, Chile.
Subsequent toxicity tests (96 h duration, 12 degrees C) were performed using
increasing effluent concentrations, a filtered seawater control, and two
potassium dichromate concentrations (to verify consistent embryonic sensitivity).
Egg mortality and hatching success were evaluated. For anchoveta, mortality (9.9
+/- 7.1%) did not significantly differ among groups in five toxicity tests except
the final toxicity test that showed significant differences in mortality (5.6%
control vs 27.8% in 100% effluent). For sardines, no differences in mortality
existed between the effluent dilutions (2.6 +/- 3.6%) and control (6.3 +/- 3.9%).
Notably, anchoveta egg survival and hatching success rates were inconsistent,
i.e., the highest rates of hatching failure occurred on the same sampling date
with the highest rates of survival for the 100% effluent group (72%). In
conclusion, the obtained results indicate that (i) anchoveta egg mortality and
hatching failure increase only under 100% effluent exposure, coinciding with
decreased egg quality near the end of spawning season and (ii) high effluent
dilutions not significantly increase sardine and anchoveta egg mortalities.
Nevertheless, the recorded adverse effects to the hatching process should be
studied in greater detail, particularly considering interspecific variability and
the complexity of reproductive processes, especially during early development.
PMID- 29946838
TI - Achieving low concentrations of chromium in drinking water by nanofiltration:
membrane performance and selection.
AB - This study evaluates nanofiltration as a feasible process to reach low
concentrations of chromium in drinking water and provides means for the selection
of the most suitable membrane based on the specific treatment needs. Chromium
removal is concerning since new stringent limits (10 MUg/L) for hexavalent Cr
concentration in potable water were recently adopted in various countries. Three
commercial nanofiltration membranes were tested against this threshold value: two
membranes made of semi-aromatic polyamide and the third having a sulfonated
polyethersulfone asymmetric film as the selective layer. The rejection observed
as a function of chemical composition in the feed solution suggests that
electrostatic effect is an important mechanism of chromium(VI) removal for the
membranes with higher surface charge and lower film density. The performance of
such membranes is strongly affected by the presence of salts, especially divalent
cations, which reduce both Cr(VI) rejection and the permeate flux. The removal of
Cr(VI) by denser membranes is dominated by solution-diffusion and is not
influenced by feed ionic strength. The exposure of membranes to high chromium
concentrations and to hypochlorite, typically employed as an oxidizing agent in
water treatment plants, was also investigated. An analysis of the operational
membrane life is thus discussed, based on the loss in performance due to active
film degradation. All three membranes showed adequate rejection of chromium from
tap and well water of diverse chemical composition, suggesting that
nanofiltration is an effective process to remove chromium for the production of
safe drinking water. However, membranes with different properties should be
adopted depending on specific feed water composition and on the productivity
required from the system. A final analysis is presented to help with the choice
of the most suitable nanofiltration membrane based on initial and target Cr(VI)
concentration in feed and product water, respectively.
PMID- 29946839
TI - Combined effects of co-exposure to formaldehyde and acrolein mixtures on
cytotoxicity and genotoxicity in vitro.
AB - FA (formaldehyde) and ACR (acrolein) are common pollutants in environment, which
often occur together in air. So, adverse health effects may not only result from
their individual toxicity but also from the combined toxicity. While often
studied alone, combination effects of these pollutants are inconclusive. Here, we
examined the combined cytotoxicity and genotoxicity of FA and ACR on A549 cells
based on CCK-8 assay, comet assay, and cytokinesis-block micronuclei assay. FA
and ACR mixtures showed significant cytotoxicity and genotoxicity even at NOECs
(no observed effect concentrations). Moreover, FA and ACR administrated jointly
at doses from NOECs to sub-cytotoxic concentrations demonstrated significant
interactions in cytotoxicity, DNA strand breaks, and chromosome damage. Co
exposure to FA and ACR significantly showed a lower responses on DNA strand break
and chromosome damage than those expected for additivity, while an opposite
result was obtained on cytotoxicity. Taken together, these results indicated that
there was significant interactions on cytotoxicity and genotoxicity for FA and
ACR, and prolonged exposure to mixtures of FA and ACR below sub-cytotoxic
concentrations can produce a serious threat in human's health.
PMID- 29946840
TI - Cyanobacterial removal by a red soil-based flocculant and its effect on
zooplankton: an experiment with deep enclosures in a tropical reservoir in China.
AB - As one kind of cheap, environmentally-friendly and efficient treatment materials
for direct control of cyanobacterial blooms, modified clays have been widely
concerned. The present study evaluated cyanobaterial removal by a red soil-based
flocculant (RSBF) with a large enclosure experiment in a tropical mesotrophic
reservoir, in which phytoplankton community was dominated by Microcystis spp. and
Anabaena spp. The flocculant was composed of red soil, chitosan and FeCl3. Twelve
enclosures were used in the experiment: three replicates for each of one control
and three treatments RSBF15 (15 mg FeCl3 l-1), RSBF25 (25 mg FeCl3 l-1), and
RSBF35 (35 mg FeCl3 l-1). The results showed that the red soil-based flocculant
can significantly remove cyanobacterial biomass and reduce concentrations of
nutrients including total nitrogen, nitrate, ammonia, total phosphorus, and
orthophosphate. Biomass of Microcystis spp. and Anabaena spp. was reduced more
efficiently (95%) than other filamentous cyanobacteria (50%). In the RSBF15
treatment, phytoplankton biomass recovered to the level of the control group
after 12 days and cyanobacteria quickly dominated. Phytoplankton biomass in the
RSBF25 treatment also recovered after 12 days, but green algae co-dominated with
cyanobacteria. A much later recovery of phytoplankton until the day of 28 was
observed under RSBF35 treatment, and cyanobacteria did no longer dominate the
phytoplankton community. The application of red soil-based flocculant greatly
reduces zooplankton, especially rotifers, however, Copepods and Cladocera
recovered fast. Generally, the red soil-based flocculant can be effective for
urgent treatments at local scales in cyanobacteria dominating systems.
PMID- 29946841
TI - Preparation and characterization of PSF/PEI/CaCO3 nanocomposite membranes for
oil/water separation.
AB - Ultrafiltration (UF) is one of the significant advanced processes for oily
wastewater treatment due to its clear advantages, for instance, ease in operation
and efficient separation. The main drawback of these processes is the fouling
problem and many researchers' effort on fabrication of high-performance membranes
with higher hydrophilicity and antifouling properties. In this study, flat-sheet
polysulfone (PSF)/polyethylenimine (PEI)/CaCO3 nanocomposite membranes were
prepared by phase inversion method for oil/water emulsion separation. Structural
properties of membranes were characterized by SEM, FT-IR, contact angle, tensile
strength, and atomic force microscopy analysis. Increasing the CaCO3 nanoparticle
loading exhibited the increased the water flux and BSA rejection. PSF/PEI/10 wt%
CaCO3 nanocomposite membranes have 145 L/m2 h water flux at 2 bar with a contact
angle of 84 degrees and with 92% BSA rejection. All prepared CaCO3 nanocomposite
membranes reached similar oil rejections at above 90%. Besides the higher water
flux and oil removal efficiencies, 10 wt% of CaCO3 nanoparticle-blended PSF
membranes has notable antifouling capacity with the highest flux recovery ratio
(FRR) and lowest flux decay ratio (DR) values. The results showed that there is a
great potential to use PSF/PEI/CaCO3 nanocomposite membranes for the treatment of
oil water emulsions with higher permeability and antifouling capacity.
PMID- 29946842
TI - Potentials of cocoa pod husk-based compost on Phytophthora pod rot disease
suppression, soil fertility, and Theobroma cacao L. growth.
AB - Cocoa black pod disease caused by Phytophthora megakarya and reduced soil
fertility are major constraints to cocoa production resulting in high yield
losses. In the absence of effective control measures and constraints related to
the use of chemical fungicides and fertilizers, there is a need to develop
additional and sustainable disease and fertilization management strategies. With
the lack of studies related to the use of compost in cocoa cultivation, the
present study aims to evaluate the potential of cocoa pod husk (CPH)-based
compost as a soil amendment to reduce the severity of cocoa black pod disease and
enhance plant growth. In vitro antagonism test showed that compost water extracts
(CWE) reduced mycelial growth with inhibition rate reaching 100% associated with
microorganisms. Disease score of cocoa plantlets grown on compost-amended soils
significantly reduced compared to plantlets grown on non-amended soil (control).
All compost rates tested significantly increased populations of actinomycetes and
fungi and biological activity in the soil. Compost application increased soil pH
and majority of the essential elements but decreased Al content, which is toxic
to cocoa growth in acidic soils. Soil application of compost at the dose of 20%
(v/v) significantly increased stem length and number of leaves compared to the
control. This study shows that CPH-based compost can not only improve soil
fertility and cocoa growth but also reduce cocoa black pod disease severity by
direct effects on inoculums level in the soil and by inducing resistance in the
plant.
PMID- 29946843
TI - Groundwater nitrate contamination and associated human health risk assessment in
southern districts of Punjab, India.
AB - Consumption of high NO3 containing water may pose serious health hazard
especially in children (< 5 years). The source of NO3 in groundwater includes
surface leaching from wastewater and waste dump sites, animal excreta disposal,
industrial effluents, and N-based fertilizers, etc. This study aimed to
investigate the concentration of NO3 in groundwater of 14 intensively cultivated
districts of Malwa Punjab, India, and its possible health hazards in local
residents. The sampling of 76 sites revealed the concentration of NO3 in ranges
of 38.45-198.05 mgL-1, and over 92% sites showed the high level of it than the
safe limits as decided by the Bureau of Indian standards (45 mg L-1) and World
Health Organization (50 mg L-1). The possible health hazards of high NO3 intake
was estimated using USEPA human health risk assessment (HHRA) model for both
adult and children. Results of this study suggested the chronic daily intake
(CDI) in the ranges of 1.09-5.65 and 2.56-13.20 in adult and children population
of this region, respectively. The hazard quotient (HQnitrate) value was > 1 in
most sampling locations ranging 1.09-5.65 for the adult and 2.56-13.20 for
children population of Malwa. This study indicates that 93.42% adult and 100%
young population of the Malwa are at higher risk of chronic toxicity by excess
NO3 intake. The HHRA results suggested a high vulnerability of a local community
to NO3 toxicity in this region; therefore, there is an instant need to take
preventive measures to safeguard the health of local residents.
PMID- 29946844
TI - The coupled study of metal concentrations and electron paramagnetic resonance
(EPR) of lichens (Hypogymnia physodes) from the Swietokrzyski National Park
environmental implications.
AB - SO2, NOx, and metals (including Cd, Cu, Pb, Zn, Mn, Mg, Fe) present in airborne
particulate matter are a major threat to preserving good air quality. The
complicated pathways and transformation processes that can change their
physical/chemical state in the atmosphere renders identifying their origin
extremely difficult. With the objective of alleviating this difficulty, we
identified and characterized potential local and regional sources of atmospheric
pollutants using bioindicators (Hypogymnia physodes) from the Swietokrzyski
National Park (SE Poland): 20 lichen samples were collected during winter
(February; heating period) and summer (June; vegetative period) seasons and
analyzed for metal contents and free radicals concentrations. Our results
indicate that the highest gaseous pollutant levels were observed during the
heating season, along roads (NO2) and at the highest elevation (SO2). The
semiquinone/phenoxyl radical concentrations correlated during the heating season
with the atmospheric SO2: ln (free radicals concentrations) = 0.025 SO2atmosphere
+ 39.11. For Mn/Fe >= 2, the electron paramagnetic resonance (EPR) spectra
presented a hyperfine splitting. Results showed that since 1994 metal
concentrations increased for Cd, Mn, and Mg, Fe remained somewhat constant for Zn
and Cu but slightly decreased for Pb, in agreement with the phasing out of lead
in gasoline. Finally, a principal component analysis (PCA) identified two main
factors controlling variability within the analyzed parameters: air pollutants
transport over long distances and local fuel combustion by both transport and
home heating.
PMID- 29946845
TI - Estrogen agonistic/antagonistic activity of brominated parabens.
AB - The estrogen agonistic/antagonistic activity of 16 brominated by-products of
parabens was assessed by using a yeast two-hybrid assay transfected with the
human estrogen receptor alpha. Characterization of synthetic compounds including
novel brominated parabens was performed using 1H-NMR spectroscopy and high
resolution mass spectrometry. For the agonist assay, five C3-C4 alkylparabens
exhibited significant activity (P < 0.05) relative to that of 17beta-estradiol,
ranging from 3.7 * 10-5 to 7.1 * 10-4. In contrast, none of the brominated alkyl
parabens exhibited agonistic activity. In the antagonist assay, 12 brominated
alkylparabens and butylparaben exhibited significant antagonistic activity (P <
0.05). Their antagonistic activity relative to 4-hydroxytamoxifen ranged from
0.11 to 2.5. The antagonist activity of C1-C4 alkylparabens increased with the
number of bromine substitutions. Benzylparaben exhibited both agonistic and
antagonistic activity, and these activities dissipated or were weakened with
increased bromination. Thus, increased bromination appeared to attenuate the
estrogen agonistic activity of most parabens such that it resulted in increased
antagonistic activity, a feature of parabens that had not been previously
described.
PMID- 29946846
TI - Effects of water temperature and light intensity on the acute toxicity of
herbicide thiobencarb to a green alga, Raphidocelis subcapitata.
AB - The present study investigated how principal environmental factors such as
temperature and light intensity change the toxicological properties of
thiobencarb (TB) herbicide to the green alga, Raphidocelis subcapitata. At first,
we investigated the inhibitory effect of TB (0, 15.6, 31.2, 62.4, and 125 MUg L
1) on growth of R. subcapitata at five temperatures (10, 15, 20, 25, or 30
degrees C) for 144 h exposure and calculated 72- and 144-h effective
concentration values (EC10, 20, and EC50) for growth rate. All EC values
significantly decreased with an increasing temperature. The maximum quantum yield
of photosystem II in R. subcapitata exposed to 125 MUg L-1 of TB was also
significantly inhibited with increased temperature. These physiological effects
could explain the lower EC values at high temperatures. Then, single and
interactive effects of TB, temperature, and light intensity on growth rate were
investigated by three-way of analysis of variance. As a result, single and
interactive effects were detected in all explanatory variables. These results
suggest that temperature and light intensity change the acute toxicity parameter
in R. subcapitata exposed to TB and must be considered in evaluating the risk of
TB.
PMID- 29946847
TI - Relationship changes between CDOM and DOC in the Songhua River affected by highly
polluted tributary, Northeast China.
AB - In this study, the dissolved organic carbon (DOC) concentrations, chromophoric
dissolved organic matter (CDOM) absorption coefficient a(254), and excitation
emission matrix fluorescence (EEM) were examined in the Songhua River (SHR) and
its highly polluted tributary of Northeast China. Fluorescence regional
integration (FRI) was used to identify five fluorescent regions: one tyrosine
like (R1), one tryptophan-like (R2), one fulvic-like (R3), one microbial by
product-like (R4), and one humic-like (R5) regions. The five EEM-FRI regions for
all water samples have site-specific properties. Principle component analysis
(PCA) was conducted to assess variations in the five FRI regions and the
humification index (HIX) for all water samples. For the water samples from the
mainstream of SHR, CDOM absorption coefficient a(254) was correlated with either
DOC or FRI fluorescent regions (R3 and R5), respectively. FRI R3 region was also
correlated with R5 region for the water samples in the mainstream of SHR.
However, the determination coefficients (R2) and slopes of these relationships
among CDOM absorption, fluorescent regions, and DOC all decreased when the SHR
waters were influenced by the highly polluted tributary of Yinma River (YMR) and
Yitong River (YTR), which has a negative effect on the estimation of DOC flux
transported by the SHR to oceans.
PMID- 29946848
TI - Environmental biotechnology and engineering: two convergent areas to provide real
solutions for a growing world.
PMID- 29946849
TI - Cancer Susceptibility Genetic Testing in a High-Risk Cohort of Urban Ashkenazi
Jewish Individuals.
AB - Prior to 2013, genetic testing for Ashkenazi Jewish (AJ) individuals primarily
consisted of the three-site BRCA1/BRCA2 AJ panel, full sequencing of BRCA1/2, or
the Lynch syndrome mismatch repair genes. Multigene panel testing became more
widely available in 2013, but limited data are available regarding the impact of
multigene panel testing for AJ individuals. Here, we report the frequency of
cancer susceptibility gene mutations in a cohort of 427 AJ individuals seen in
the Cancer Risk Clinic at The University of Chicago. We found that 29% of
affected and 37% of unaffected individuals carried a pathogenic mutation (32% of
overall cohort), primarily known familial mutations in BRCA1/2. A minority of
mutations were identified in non-BRCA1/2 genes and consisted mainly of AJ founder
mutations in CHEK2, APC, and the mismatch repair genes. A panel of AJ founder
mutations would have identified the majority (94%) of mutations in clinically
actionable genes in both affected and unaffected patients. Based on recent cost
effectiveness studies, offering all AJ individuals a founder mutation panel may
be a cost-effective cancer prevention strategy.
PMID- 29946850
TI - Autochthonous acute hepatitis E: treatment with sofosbuvir and ribavirin.
AB - INTRODUCTION: Hepatitis E virus (HEV) is an emerging cause of autochthonous-acute
hepatitis and acute-on-chronic-liver-failure in western countries. Treatment is
not routinely used, despite ribavirin has a good antiviral effect. In vitro
sofosbuvir inhibits HEV replication, but clinical data are lacking. CASE REPORT:
We report a case of acute-on-chronic-liver-failure due to HEV treated with
sofosbuvir and ribavirin. The treatment was capable of rapidly inducing both HCV
and HEV viral suppression. CONCLUSION: In conclusion, although more data are
required before firm conclusions could be drawn, the combination of sofosbuvir
and ribavirin in not immunosuppressed patients with acute hepatitis E may be able
to clear HEV infection.
PMID- 29946851
TI - [Journal Club : A new format in Der Pathologe].
PMID- 29946852
TI - [Neuroendocrine prostate cancer].
AB - Neuroendocrine prostate cancer (NEPC) mostly occurs as a treatment-emergent
adaptive response under the pressure of intensive androgen deprivation treatment
(t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant
prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary
small cell prostate cancer is very rare (<1%). A t-NEPC should be clinically
suspected in patients who have particularly aggressive mCRPC but a
disproportionately low prostate-specific antigen (PSA) level and elevated
neuroendocrine tumor markers, such as chromogranin A and neuron-specific enolase.
The initial Gleason score was shown to be an independent factor correlated to the
risk of development of t-NEPC. Treatment is oriented to that of small cell lung
cancer. In patients with negative PSA levels, chemotherapy with cisplatin and
etoposide is the first line treatment, for which response rates in the range of
30-60% with a median survival time of usually less than 1 year can be achieved.
In patients with much higher serum PSA levels, chemotherapy with carboplatin plus
docetaxel should be considered.
PMID- 29946854
TI - Successful treatment of cytarabine-related neurotoxicity with corticosteroids, a
case series.
AB - Neurotoxicity from high-dose cytarabine, a pyrimidine metabolite used in
treatment for acute myeloid leukemia, is a known but dose-limiting toxicity which
has incidences in up to 14% in patients receiving high doses of the drug.
Neurologic symptoms vary but range from somnolence and ataxia to more severe
complications such as seizures and even death. There are no validated treatments
other than discontinuation of the drug and supportive measures. We present two
cases of cytarabine-related neurotoxicity treated with corticosteroids with
complete resolution of symptoms.
PMID- 29946855
TI - The occurrence of adverse events in low-risk non-survivors in pediatric intensive
care patients: an exploratory study.
AB - : We studied the occurrence of adverse events (AEs) in low-risk non-survivors
(LNs), compared to low-risk survivors (LSs), high-risk non-survivors (HNs), and
high-risk survivors (HSs) in two pediatric intensive care units (PICUs). The
study was performed as a retrospective patient record review study, using a PICU
trigger tool. A random sample of 48 PICU patients (0-18 years) was chosen,
stratified into four subgroups of 12 patients: LNs, LSs, HNs, and HSs. Primary
outcome was the occurrence of AEs. The severity, preventability, and nature of
the indentified AEs were determined. In total, 45 AEs were found in 20 patients.
The occurrence of AEs in the LN group was significantly higher compared to that
in the LS group and HN group (AE occurrence: LN 10/12 patients, LS 1/12 patients;
HN 2/12 patients; HS 7/12 patients; LN-LS difference, p < 0.001; LN-HN
difference, p < 0.01). The AE rate in the LN group was significantly higher
compared to that in the LS and HN groups (median [IQR]: LN 0.12 [0.07-0.29], LS 0
[0-0], HN 0 [0-0], and HS 0.03 [0.0-0.17] AE/PICU day; LN-LS difference, p <
0.001; LN-HN difference, p < 0.01). The distribution of the AEs among the four
groups was as follows: 25 AEs (LN), 2 AEs (LS), 8 AEs (HN), and 10 AEs (HS).
Fifteen of forty-five AEs were preventable. In 2/12 LN patients, death occurred
after a preventable AE. CONCLUSION: The occurrence of AEs in LNs was higher
compared to that in LSs and HNs. Some AEs were severe and preventable and
contributed to mortality. What is Known: * 59-76% of all PICU patients encounter
at least one adverse event during their PICU stay. * It is unknown if adverse
events play a role in death of low-risk PICU patients. What is New: * In low-risk
PICU non-survivors, occurrence of adverse events is higher compared to low-risk
PICU survivors and to high-risk PICU non-survivors. * Severe and preventable
adverse events occur in low-risk PICU non-survivors, some contributing to
mortality.
PMID- 29946856
TI - Child trafficking in Europe: what is the paediatrician's role? : A statement by
the European Academy of Paediatrics.
AB - : Child trafficking is among the most lucrative criminal activities in the world
and growing rapidly. Poverty, natural disasters, armed conflicts and, in
particular, migration put vulnerable children at high risk of trafficking.
Accurate statistics on child trafficking are not available due to its illegal
nature. Moreover, trafficking may not be consistently recorded and reported by
European countries, mainly because of different perceptions as to who is
considered a victim of trafficking. Around 4000-5000 children were identified as
presumed victims of trafficking in European Union countries from 2013 to 2014;
this is an underestimate of the problem because many victims go unrecognised.
Trafficking is linked with issues, such as forced marriage, begging, labour or
domestic servitude, slavery and prostitution as well as sexual abuse and child
pornography. It may also involve the use of children as soldiers or for criminal
activities, such as theft and drug smuggling. Child trafficking also involves the
removal of organs and the selling neonates, infants, and children for adoption.
Child victims of trafficking should be promptly identified in order to provide
them with the necessary care as well as to prosecute the traffickers and stop
their illegal activity. Healthcare professionals should be appropriately trained
to keep a careful eye out for any signs of trafficking in children. CONCLUSION:
The European Academy of Paediatrics calls on our governments, intergovernmental
organisations, paediatricians, and healthcare professionals to collaborate so as
to improve the identification and healthcare of victims and to contribute to the
disbanding and prosecution of child traffickers by reporting such situations.
What is Known: * Child trafficking is a fast growing and among the most lucrative
criminal activities in the world. * Poverty, natural disasters, armed conflicts
and in particular migration put vulnerable children at high risk of trafficking.
What is New: * Child trafficking is an underestimated and often ignored issue,
with around 4000-500children identified as presumed victims in European Union
countries from 2013 to 2014. * The European Academy of Paediatrics strongly
encourages Paediatricians to identify victims as well as provide them with
adequate health care and support; it calls on governments, intergovernmental
organisations, and fellow compatriots to act within the full extent of the law to
identify, disband, and prosecute child traffickers.
PMID- 29946857
TI - Implementation of the Sepsis-3 definition in German university intensive care
units : A survey.
AB - BACKGROUND: The old definition of sepsis was replaced by Sepsis-3 in February
2016. The new screening diagnostic tools sequential organ failure assessment
(SOFA) score and quick SOFA (qSOFA) score were incorporated into the definition.
The resulting scientific controversy led to several retrospective and prospective
evaluations. In contrast no evaluation of the state of play of national
implementation of Sepsis-3 has been conducted so far. OBJECTIVE: The aim of this
study was to capture the current situation in German academic intensive care
units 1 year after the implementation of Sepsis-3. METHODS: An internet-based
questionnaire consisting of 22 items was developed. The identification of
eligible departments was performed by an online search of the homepages of all
university hospitals located in Germany. Departments regardless of the discipline
with an explicit indication of involvement in intensive care were extracted. The
link to the internet-based questionnaire was sent to all identified departments
on 22 February 2017 and was accessible for 19 days. RESULTS: Out of 259
departments 76 answered the online survey. The response rate was 29.3% from 13
specializations. Anesthesiology, internal medicine and general surgery were the
three main participants in this study. The majority of intensive care units
(54.75%) treated more than 100 patients with sepsis or septic shock annually and
more than 30% treated more than 250 patients. While 76.7% of respondents had a
standard operating procedure, 55% of those were based on the Sepsis-3 definition.
When asked to rate the usefulness of the Sepsis-3 definition, answers were
heterogeneous with a slight tendency towards a higher usefulness and the majority
(72.9%) were in favor of Sepsis-3 being included in the national S2K guidelines.
CONCLUSION: The results demonstrate the heterogeneity of Sepsis-3 implementation
in German intensive care units. Sepsis-3 is finding its way but there is a need
for standardized implementation.
PMID- 29946858
TI - The health hazards of potentially toxic metals in the daily diets of adults and
children from a mining and smelting region (Hezhang County) in southwestern
China.
AB - Toxic metals accumulated in the human body are predominantly absorbed by the
digestive tract in non-occupationally exposed populations. In the current study,
we collected plowed soil samples, and investigated the varied food compositions
in a mining and smelting area in southwestern China, to measure the
concentrations of ten potentially toxic metals-As, Ba, Cd, Cr, Cu, Mn, Ni, Pb,
Sr, and Zn. We collected information on the daily intakes of these metals to
assess the health risks associated with their exposure among children and adults.
The urine concentrations of the metals were also measured to obtain data on the
amounts present in the body. The results showed that the hazard indexes (HIs) of
As, Ba, Cd, Cr, Ni, Pb, and Sr were all larger than 1, for both adults and
children; the Zn and Cu values were comparatively higher in children. The intake
of staple foods of the region posed the greatest health risk, while drinking
water only posed risks clearly associated with As exposure. The urine samples of
local residents contained larger amounts of As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn,
confirming the hazards in the health risk assessment. Obvious differences in the
urine metal concentrations between men and women were confirmed. In conclusion,
higher concentrations of metals in the surface soil and rain water were the
predominant cause of elevated exposure through home-grown crops and produce to
accumulate in local residents' bodies.
PMID- 29946859
TI - An observational study on the sub-acute effects of mephedrone on mood, cognition,
sleep and physical problems in regular mephedrone users.
AB - RATIONALE: Mephedrone (4-methylmethcathinone; 4-MMC) is a novel recreational drug
similar to methylenedioxymethamphetamine (MDMA) and amphetamine. Several adverse
effects have been reported, but little is known about its sub-acute effects.
OBJECTIVES: To study sub-acute effects of mephedrone over a period of 9 days.
METHODS: Recreational mephedrone users were recruited and followed over a time
period of 9 days. It was recorded whether participants consumed mephedrone or not
within the period of testing; those who did were compared to those who did not.
Forty-six regular mephedrone users (22 males, 24 females) participated, 21
participants voluntarily opted to consume mephedrone 1-3 days after baseline and
25 opted to abstain. Participants were assessed at baseline on a multitude of
measures and provided daily reports on cognition, sleep, mood, physical problems,
mephedrone cravings and substance use on each subsequent day of the study. The
study controlled for psychopathology, sleep, past and current substance use,
impulsivity and demographics. RESULTS: Those who consumed mephedrone reported
persistent negative mood, physical problems and fatigue, compared to those who
did not-after controlling for baseline group differences in sleep and subsequent
alcohol and cannabis use. CONCLUSIONS: The results provide the first prospective
evidence of the duration and extent of specific undesirable sub-acute effects of
mephedrone in regular recreational users and indicate sub-acute effects of
mephedrone on mood, fatigue and physical symptoms.
PMID- 29946860
TI - Long-term oncological outcomes following emergency resection of colon cancer.
AB - PURPOSE: The relationship between emergency colon cancer resection and long-term
oncological outcomes is not well understood. Our objective was to characterize
the impact of emergency resection for colon cancer on disease-free and overall
patient survival. METHODS: Data on patients undergoing resection for colon cancer
from 2006 to 2015 were collected from a prospectively maintained clinical and
administrative database. The median follow-up time was 4.4 years. Cox
proportional hazards models were used to estimate the hazard ratios for
recurrence and death for patients treated with surgery for an emergent
presentation. Differences in initiation of, and timeliness of, adjuvant
chemotherapy between emergently and electively treated patients were also
examined. RESULTS: Of the 1180 patients who underwent resection for stages I, II,
or III colon cancer, 158 (13%) had emergent surgery. After adjustment for
patient, tumor, and treatment characteristics, the HR for recurrence was 1.64
(95% CI 1.12-2.40) and for death was 1.47 (95% CI 1.10-1.97). After adjustment
for tumor characteristics, patients who underwent emergency resection were
similarly likely to receive adjuvant chemotherapy (OR 1.1; 95% CI 0.70-1.76). The
time from surgery to initiation of adjuvant chemotherapy was also similar between
the groups. CONCLUSIONS: Emergency surgery for localized or regional colon cancer
is associated with a greater risk of recurrence and death. This association does
not appear to be due to differences in adjuvant treatment. A focus on screening
and colon cancer awareness in order to reduce emergency presentations is
warranted.
PMID- 29946861
TI - Adsorption of copper (II) on mesoporous silica: the effect of nano-scale
confinement.
AB - Nano-scale spatial confinement can alter chemistry at mineral-water interfaces.
These nano-scale confinement effects can lead to anomalous fate and transport
behavior of aqueous metal species. When a fluid resides in a nanoporous
environments (pore size under 100 nm), the observed density, surface tension, and
dielectric constant diverge from those measured in the bulk. To evaluate the
impact of nano-scale confinement on the adsorption of copper (Cu2+), we performed
batch adsorption studies using mesoporous silica. Mesoporous silica with the
narrow distribution of pore diameters (SBA-15; 8, 6, and 4 nm pore diameters) was
chosen since the silanol functional groups are typical to surface environments.
Batch adsorption isotherms were fit with adsorption models (Langmuir, Freundlich,
and Dubinin-Radushkevich) and adsorption kinetic data were fit to a pseudo-first
order reaction model. We found that with decreasing pore size, the maximum
surface area-normalized uptake of Cu2+ increased. The pseudo-first-order kinetic
model demonstrates that the adsorption is faster as the pore size decreases from
8 to 4 nm. We attribute these effects to the deviations in fundamental water
properties as pore diameter decreases. In particular, these effects are most
notable in SBA-15 with a 4-nm pore where the changes in water properties may be
responsible for the enhanced Cu mobility, and therefore, faster Cu adsorption
kinetics.
PMID- 29946862
TI - Estrogen-receptor status and risk of contralateral breast cancer following DCIS.
AB - PURPOSE: As local therapies improve, contralateral breast cancer (CBC) risk for
women with ductal carcinoma in situ (DCIS) may exceed the risk of a second
ipsilateral breast cancer. We sought to determine whether estrogen-receptor (ER)
status influenced CBC risk. METHODS: We identified women aged 40-79 with DCIS
diagnosed between 1990 and 2002 using the Surveillance, Epidemiology, and End
Results database. We used multivariable competing risk regression to examine
predictors of time from index DCIS to CBC (invasive or in situ). RESULTS:
Multivariable competing risk regression found ER status to be a highly
significant predictor of CBC. The 10-year cumulative incidence was estimated to
be 5.3% (95% CI 4.8-5.8%) among ER positive (ER+) cases and 3.3% (95% CI 2.6
4.0%) among ER negative (ER-). CONCLUSIONS: This finding suggests that ER+ DCIS
may represent a field effect that confers increased propensity for developing
cancer across breast tissue, regardless of laterality. In contrast, ER- DCIS may
represent an isolated local event. Given that the majority of DCIS is ER+, and
only a minority of DCIS patients receive hormonal therapy, consideration of ER
status may influence treatment and surveillance approaches.
PMID- 29946864
TI - Key role of renal biopsy in management of progressive chronic kidney disease in
liver graft recipients.
AB - AIMS: Chronic kidney disease (CKD) is a common complication after liver
transplantation (LT). The etiology of CKD is broad and may only be assessed
accurately by renal histology. The current study aimed to analyze the safety of
renal biopsy in daily clinical practice as well as its usefulness regarding
management of CKD after LT. METHODS: We performed a retrospective analysis of
clinical data and renal biopsies obtained from patients with severe renal
impairment (overt proteinuria, progressive deterioration of renal function) after
LT with respect to safety, etiology of renal disease, and therapeutic
consequences. RESULTS: Renal biopsies were obtained from 14 patients at median
(minimum-maximum) 3 (0.2-12) years after LT. No major complications associated
with renal biopsy were observed. Histomorphological alterations were varied
(nephrosclerosis, n = 5; IgA-glomerulonephritis, n = 4; tenofovir-associated
nephropathy, membranoproliferative glomerulonephritis type 1, membranous
glomerulonephritis, amyloid A amyloidosis, and calcineurin inhibitor nephropathy,
n = 1, respectively). The diagnosis of specific renal diseases other than
calcineurin-inhibitor nephrotoxicity facilitated specific treaments and avoided
unnecessary modification of immunosuppression in the majority of patients.
CONCLUSIONS: Renal biopsy in patients with CKD after LT seems safe and may offer
specific therapeutic options. Furthermore, unnecessary changes of
immunosuppression can be avoided in a considerable number of patients.
PMID- 29946865
TI - Health Insurance Coverage and Access to Care Among US-Born and Foreign-Born
Sexual Minorities.
AB - Sexual minorities and immigrants face unique challenges to accessing health care
in the United States. This study used data on nonelderly adults (n = 100,667)
from the 2013-2016 National Health Interview Survey. Unadjusted prevalence
estimates and multivariable logistic regression models (with and without
interactions between immigration and sexual minority status) were used to compare
health insurance coverage and access to care by immigration and sexual minority
status. We did not find any differences in uninsurance, having a usual source of
care, and a recent office visit by sexual orientation for US-born and foreign
born adults. However, compared to their heterosexual counterparts, US-born and
foreign-born sexual minorities were more likely to have an emergency room visit
in the prior year and report financial-related barriers to medical care, dental
care, prescription medications, and mental health care. Foreign-born sexual
minorities were more likely to have an emergency room visit and unmet mental
health care needs due to cost compared to other subpopulations after controlling
for sociodemographic characteristics. Broadening the knowledge and scope of
research on sexual minority immigrants can inform targeted health policy
approaches with the goal of achieving health equity for sexual minority
immigrants.
PMID- 29946863
TI - Pharmacometabolomics reveals a role for histidine, phenylalanine, and threonine
in the development of paclitaxel-induced peripheral neuropathy.
AB - PURPOSE: Approximately 25% of breast cancer patients experience treatment delays
or discontinuation due to paclitaxel-induced peripheral neuropathy (PN).
Currently, there are no predictive biomarkers of PN. Pharmacometabolomics is an
informative tool for biomarker discovery of drug toxicity. We conducted a
secondary whole blood pharmacometabolomics analysis to assess the association
between pretreatment metabolome, early treatment-induced metabolic changes, and
the development of PN. METHODS: Whole blood samples were collected pre-treatment
(BL), just before the end of the first paclitaxel infusion (EOI), and 24 h after
the first infusion (24H) from sixty patients with breast cancer receiving (80
mg/m2) weekly treatment. Neuropathy was assessed at BL and prior to each infusion
using the sensory subscale (CIPN8) of the EORTC CIPN20 questionnaire. Blood
metabolites were quantified from 1-D-1H-nuclear magnetic resonance spectra using
Chenomx(r) software. Metabolite concentrations were normalized in preparation for
Pearson correlation and one-way repeated measures ANOVA with multiple comparisons
corrected by false discovery rate (FDR). RESULTS: Pretreatment histidine,
phenylalanine, and threonine concentrations were inversely associated with
maximum change in CIPN8 (DeltaCIPN8) (p < 0.02; FDR <= 25%). Paclitaxel caused a
significant change in concentrations of 2-hydroxybutyrate, 3-hydroxybutyrate,
pyruvate, o-acetylcarnitine, and several amino acids from BL to EOI and/or 24H (p
< 0.05; FDR <= 25%), although these changes were not associated with DeltaCIPN8.
CONCLUSIONS: Whole blood metabolomics is a feasible approach to identify
potential biomarker candidates of paclitaxel-induced PN. The findings suggest
that pretreatment concentrations of histidine, phenylalanine, and threonine may
be predictive of the severity of future PN and paclitaxel-induced metabolic
changes may be related to disruption of energy homeostasis.
PMID- 29946866
TI - Challenges in Recruiting African-Born, US-Based Participants for HIV and
Tuberculosis Research.
AB - Research is critical for developing HIV and tuberculosis (TB) programming for
U.S. African-born communities, and depends on successful recruitment of African
born people. From January 2014 to June 2016, we recruited African-born people for
HIV and TB research in King County, Washington. We compared the characteristics
of study participants and the underlying populations of interest, and assessed
recruitment strategies. Target enrollment for the HIV study was 167 participants;
51 participants (31%) were enrolled. Target enrollment for the TB study was 218
participants; 38 (17%) were successfully recruited. Of 249 prior TB patients we
attempted to contact by phone, we reached 72 (33%). Multiple recruitment
strategies were employed with variable impact. Study participants differed from
the underlying populations in terms of gender, country of origin and language.
Inequities in research participation and in meaningful opportunities for such
participation may exacerbate existing health disparities.
PMID- 29946867
TI - Silver nanoparticles supported onto a stainless steel wire for direct-immersion
solid-phase microextraction of polycyclic aromatic hydrocarbons prior to their
determination by GC-FID.
AB - The authors describe a new coating for use in solid-phase microextraction (SPME).
Silver nanoparticles (AgNPs) were prepared by using gallic acid or glucose as the
reducing agents, and then supported onto a stainless steel wire that was
previously coated with a silver mirror. Coating with AgNPs was performed by a
layer-by-layer approach of up to eight cycles of consecutive deposition of AgNPs
and the thiol linker 1,8-octanedithiol. This procedure allows proper control of
the coating thickness. Thicknesses are 3.2 MUm and 3.5 MUm with AgNPs obtained
with gallic acid and glucose, respectively. This is in agreement with theoretical
estimations (3.8 MUm). The fibers were used in the direct-immersion SPME-GC-FID
determination of 16 polycyclic aromatic hydrocarbons (PAHs) from different
waters. The performance of the method was compared to the one using
polydimethylsiloxane fibers (100 MUm), which is the most suitable commercial SPME
fiber for PAHs. Despite the low thickness of the AgNP coatings (compared to
PDMS), the analytical features of the method using the most adequate coating
(AgNPs prepared with gallic acid) include: (a) limits of detection down to 0.6
ng.mL-1; (b) intra-day, inter-day, and inter-fiber precisions (expressed as RSDs)
lower than 22, 26 and 25%, respectively; and (c) an operational lifetime of ~150
extractions/desorption cycles. The analysis of various spiked environmental
waters using these fibers resulted in adequate analytical performance. Graphical
abstract Silver nanoparticle based coatings for solid-phase microextraction
fibers were prepared by a layer-by-layer approach. They were used for
determination of 16 PAHs in waters by gas chromatography. Limits of detection are
< 14 MUg.L-1 and intra-day, inter-day, and inter-fiber precisions are <26%.
PMID- 29946868
TI - An epigenetic regulatory switch controlling temperature-dependent sex
determination in vertebrates.
PMID- 29946869
TI - Comprehensive immunohistochemical analyses on expression levels of hedgehog
signaling molecules in breast cancers.
AB - BACKGROUND: The hedgehog (Hh) signaling pathway plays important roles in cell
proliferation, malignant progression, invasion and metastasis, and the expansion
of cancer stem cells (CSCs). Comprehensive immunohistochemical (IHC) analyses
have not yet been conducted on the expression levels of Hh signaling molecules in
breast cancer tissues. METHODS: A total of 204 patients with invasive breast
cancer treated in our institute were study subjects. IHC analyses on the
expression levels of the Hh signaling molecules, sonic Hh (SHH), PTCH1, GLI1,
GLI2, and GLI3 and the CSC-related factor, SOX2, were investigated. RESULTS:
Positive correlations were observed among all of the Hh signaling molecules
tested. SOX2 expression correlated with the expression levels of all Hh signaling
molecules. SHH expression positively correlated with tumor size, the Ki-67
labeling index, histological grade, estrogen receptor negativity, progesterone
receptor negativity, and HER2 positivity. GLI1 expression positively correlated
with the histological grade. GLI2 expression positively correlated with the
histological grade, Ki-67 labeling index, and HER2 positivity. Univariate
analyses revealed that a younger age, larger tumor size, positive lymph node
metastasis, higher histological grade, positive lymphatic invasion, and higher Ki
67 labeling index were related to poor relapse-free survival (RFS). The
positivity of all Hh signaling molecules and SOX2 did not correlate with poor
RFS. A multivariate analysis revealed that positive lymphatic invasion and a
younger age were independent worse prognostic factors for RFS. CONCLUSIONS: This
comprehensive analysis demonstrated for the first time that SHH, GLI1, and GLI2
expression levels positively correlated with the malignant phenotypes of tumor
cells.
PMID- 29946870
TI - Comment on van Rongen et al., "Higher Midazolam Clearance in Obese Adolescents
Compared with Morbidly Obese Adults".
PMID- 29946871
TI - A Positive Correlation Between Gastric and Esophageal Dysmotility Suggests Common
Causality.
AB - BACKGROUND: Gastric and esophageal dysmotility syndromes are some of the most
common motility diagnoses, but little is known about their interrelationship.
AIMS: The aim of our study was to determine if a correlation exists between
gastric and esophageal dysmotility syndromes. METHODS: We reviewed the records of
all patients who underwent both solid gastric emptying scintigraphy (GES) and
high-resolution esophageal manometry (HRM) within a 2 year period, with both done
between August 2012 and August 2017. All GESs were classified as either rapid,
normal, or delayed. All HRMs were classified according to the Chicago
Classification 3.0. Correlations were assessed using Fisher's exact test and
multiple logistic regression. RESULTS: In total, 482 patients met inclusion
criteria. Of patients with a normal, delayed, and rapid GES, 53.1, 64.5, and
77.3% had an abnormal HRM, respectively (p < 0.05 vs. normal GES). Likewise,
patients with an abnormal HRM were more likely to have an abnormal GES (54.9 vs.
41.8%, p = 0.005). Multiple logistic regression showed abnormal GES [odds ratio
(OR) 2.14], age (OR 1.013), scleroderma (OR 6.29), and dysphagia (OR 2.63) were
independent predictors of an abnormal HRM. Likewise, an abnormal HRM (OR 2.11),
diabetes (OR 1.85), heart or lung transplantation (OR 2.61), and autonomic
dysfunction (OR 2.37) were independent predictors of an abnormal GES.
CONCLUSIONS: The correlation between an abnormal GES and HRM argues for common
pathogenic mechanisms of these motility disorders, and possibly common future
treatment options. Clinicians should have a high index of suspicion for another
motility disorder if one is present.
PMID- 29946872
TI - Frequency of Celiac Disease in Children with Peptic Ulcers.
AB - AIM: The aim of the present study is to investigate the frequency of celiac
disease in children with peptic ulcers and to compare it with that of non-celiac
peptic ulcers in terms of clinical and laboratory values. METHODS: Upper
gastrointestinal endoscopy was performed in 1769 patients at the Department of
Pediatric Gastroenterology, The Faculty of Medicine, Cukurova University, Turkey,
between January 2012 and January 2017. These cases consisted of subjects
presenting with various GIS symptoms and indicated for endoscopy (with chronic
diarrhea, delayed growth and development, abdominal pains, GIS bleeding, etc.).
The levels of immunoglobulin A (IgA) serum anti-tissue transglutaminase
antibodies, IgA anti-endomysial antibodies (EMA), and IgA serum were estimated in
the patients with peptic ulcers. RESULTS: Celiac disease was diagnosed with
serology, endoscopy, and histopathology in 250 (14%) of all cases undergoing
endoscopy. Peptic ulcers were diagnosed in 74 patients (4.2%) of all cases
undergoing endoscopy. tTGA and EMA (+) levels were determined in 22 (29%) of the
74 patients with peptic ulcers, and then the presence of peptic ulcers was
investigated in the upper gastrointestinal system using gastrointestinal
endoscopy, followed by histopathological confirmation of celiac disease. HP
infection was present in 14 (63%) of the patients with celiac disease and in 23
(44%) of non-celiac peptic ulcers; the difference was not statistically
significant (p = 0.12). In the total ulcer group, 10.8% (8/74) of patients with
celiac peptic ulcers were negative for HP infection, whereas 21% (8/37) of HP
negative patients with ulcers had celiac disease. CONCLUSION: There exists a high
risk of celiac disease in children with peptic ulcers. We thus recommend celiac
disease to be investigated, particularly in HP-negative patients with peptic
ulcers but with no history of NSAID use.
PMID- 29946873
TI - Hot Compress with Chinese Herbal Salt Packets Reducing PICC Catheter
Complications: A Randomized Controlled Trial.
AB - OBJECTIVE: To explore the preventive effect of applying hot compress with Chinese
herbal salt packets (CHSP) to puncture vessels under aseptic conditions during
peripherally inserted central catheter (PICC) on postoperative phlebitis.
METHODS: A total of 720 hospitalized patients undergoing first PICC were assigned
to treatment and control groups (360 cases each group) according to a random
number table. The control group received conventional catheterization and nursing
care. The treatment group was first given hot compress with CHSP (which consisted
of honeysuckle 30 g, Semen brassicae 30 g, Salvia miltiorrhiza 30 g, Angelica
dahurica 30 g, Semen raphani 30 g, Evodia rutaecarpa 30 g, and coarse salt 20 g)
on the punctured vessel under aseptic conditions for 5-10 min before conventional
catheterization. The main efficacy indices were the vessel diameters before and
during catheterization and the success rate of a single catheter, and the
secondary efficacy indiex was the incidence of superficial phlebitis within 1
week after catheterization. RESULTS: The vessel diameter during catheterization
of the treatment group was remarkably increased compared with the control group
[(7.96+/-0.42) mm vs. (4.39+/-0.54) mm, P<0.01]. The success rate of the single
catheter of the treatment group was significantly higher than that of the control
group [94.00% (329/350) vs. 73.72% (244/329), P<0.01]. The incidence of
superficial phlebitis within 1 week after catheterization in the treatment group
was lower than that in the control group (P=0.007). There was no adverse event
with CHSP. CONCLUSION: Hot compress with CHSP during PICC is applicable as it can
effectively improve the success rate of a single catheter and reduce the
incidence of superficial phlebitis after catheterization (Trial registration No.
ChiCTR-ONC-17010498).
PMID- 29946874
TI - [Bridging anticoagulation in patients receiving vitamin K antagonists : Current
status].
AB - Approximately 30% of patients receiving oral anticoagulation using vitamin K
antagonists (VKA) require surgery within 2 years. In this context, a clinical
decision on the need and the mode of a peri-interventional bridging with heparin
is needed. While a few years ago, bridging was almost considered a standard of
care, recent study results triggered a discussion on which patients will need
bridging at all. Revisiting the currently available recommendations and study
results the conclusion can be drawn that the indications for bridging with
heparin must nowadays be taken more narrowly and considering the individual
patient risk of bleeding and thromboembolism. Bridging with heparin is only
needed in patients with a very high risk of thromboembolism. This overview aims
to give guidance for a risk-adapted peri-interventional approach to management of
patients with a need for long-term anticoagulation using VKA.
PMID- 29946875
TI - [Pathophysiology and treatment of IgA nephropathy].
AB - The IgA nephropathy is the most frequent form of glomerulonephritis worldwide. In
approximately 30% of patients a reduction in the glomerular filtration rate of
approximately 50% is observed within 10 years. Patients with IgA nephropathy form
IgG autoantibodies against galactose-deficient IgA1 antibodies. This results in
deposition of these antibodies in the mesangium and activation of complement with
mesangial hypercellularity, endocapillary hypercellularity, segmental
glomerulosclerosis and atrophying interstitial fibrosis. The basic treatment for
patients with IgA nephropathy consists of removing risk factors, in particular
hypertension, with blockade of the renin-angiotensin-aldosterone system.
Immunosuppressives were also investigated in various studies but a clear
advantage was not observed.
PMID- 29946879
TI - Progression of dialysis-related amyloidoma towards pathologic fracture.
AB - Amyloidosis is the extracellular deposition of amyloid protein fibrils, and this
condition may be hereditary or acquired. Patients undergoing long-term
hemodialysis are particularly at risk for developing acquired amyloidosis. A rare
form of amyloidosis is an amyloidoma or amyloid tumor, which occurs when amyloid
focally deposits in a section of the musculoskeletal system, most commonly in the
osteoarticular system. Here, we present a case of a hemodialysis-related
amyloidoma of the left femoral neck in an 80-year-old woman with end-stage renal
disease on hemodialysis for 8 years. The purpose of this report is to provide an
account of the unique clinical, imaging, and histopathologic manifestation of a
dialysis-related amyloidoma that progressively enlarges over a 2-year period.
This report also highlights some prophylactic measures that may reduce the risk
of developing an associated pathologic fracture.
PMID- 29946880
TI - Painful swelling in the proximal third of the arm.
PMID- 29946881
TI - Comparison of unidirectional and circumferential manometric measures within the
pharyngoesophageal segment: an exploratory study.
AB - BACKGROUND: Notable differences have been identified between low-resolution
manometry (LRM) and high-resolution manometry (HRM) in normative data. OBJECTIVE:
This study aimed to investigate within-subject differences between unidirectional
LRM and circumferential HRM solid-state measurement sensors in the
pharyngoesophageal segment during swallowing. METHODS: Ten healthy subjects (mean
26.9 years) were evaluated with both a 2.10 mm unidirectional catheter and a 2.75
mm circumferential catheter, with randomized order of catheter placement.
Unidirectional measurements were made in four directions (posterior, anterior,
right-lateral, left-lateral). Pressures and durations were analyzed to compare
(1) posterior to anterior and lateral recordings and (2) posterior and average
LRM measures (C-LRM) to HRM measures at same anatomical location. RESULTS: No
significant differences were found in any of the measures across the four radial
directions. A lower amplitude was measured in C-LRM compared to HRM for
pharyngeal sensors (LRM Sensor 1: - 39.7 mmHg; Sensor 2: - 61.4 mmHg). Compared
with posterior-LRM, HRM recorded higher UES pressures (- 12.8 mmHg) and longer
UES relaxation durations (- 0.31 s). CONCLUSION: This exploratory study is the
first to compare within-subject pressures between unidirectional LRM and
circumferential HRM. Substantial differences in pharyngeal manometric measures
were found, particularly with regard to UES function. This is clinically
important as manometry is uniquely able to evaluate UES function and clarify
differential diagnoses in patients with dysphagia.
PMID- 29946882
TI - Correction to: Osteogenic prospective of deriving human dental stem cells in
collagen matrix boost.
AB - The original version of this article unfortunately contained a mistake. The
country was incorrect in the authors affiliations. It should read as "ROC". The
corrected affiliations are given below.
PMID- 29946883
TI - [Rational use of genetic tests in internal medicine : Possibilities and
limitations of next generation sequencing diagnostics].
AB - BACKGROUND: New methods of molecular genetic diagnostics enable a more
comprehensive genetic analysis of patients. OBJECTIVES: Rational use and benefits
of molecular genetic testing in patients with various internal diseases. METHOD:
Evaluation of topic-related literature, discussion of own experiences, as well as
consideration of current guidelines. RESULTS: New genetic tests, such as next
generation sequencing (NGS), improve the diagnosis of hereditary diseases;
however, the use of this technology also leads to additional findings, which must
be carefully considered. CONCLUSION: The rational use of genetic tests is a
benefit for patients and can significantly influence the prevention and treatment
of a disease. The increasing complexity of genetic findings requires
interdisciplinary approaches involving human genetics, internal medicine, and
other disciplines.
PMID- 29946885
TI - Performance evaluation of 1-D numerical model HEC-RAS towards modeling sediment
depositions and sediment flushing operations for the reservoirs.
AB - Sediment inflow to the reservoir is a key factor to calculate life of the
reservoir. Flushing is a very useful technique in order to enhance the life of
reservoir. From the literature review, 14 reservoirs were considered where
flushing has already been practiced and only 6 reservoirs were found successful
in flushing. The others were found partially flushed. In this research, data of
three successfully flushed reservoirs namely Baira reservoir (India), Gebidem
reservoir (Switzerland), and Gmund reservoir (Austria) were used to run 1-D
numerical model HEC-RAS. In the first phase, the longitudinal profiles of delta
were modeled and calibrated with observed sediment depositions. In the presence
of available data of discharges and respective reservoir levels, the modeled
deltas were used for flushing the deltas. With the help of modeled delta and
corresponding flushing discharges, sediment deposition and flushing durations
were computed. The simulated flushed durations were 31, 102, and 180 h for Baira,
Gebidem, and Gmund reservoirs, respectively. The simulated flushed durations were
found close to observed durations. Hence, the use of 1-D numerical model HEC-RAS
is encouraged for modeling of sediment deposits and flushing operations.
PMID- 29946886
TI - Peer-Influence on Risk-Taking in Male Adolescents with Mild to Borderline
Intellectual Disabilities and/or Behavior Disorders.
AB - This study aimed to disentangle the effects of Mild-to-Borderline Intellectual
Disability (MBID) and Behavior Disorders (BD)on risk taking in circumstances
where peer influence was absent or present. We studied 319 adolescents in four
groups: MBID-only, MBID+BD, BD-only, and typically developing controls. The
Balloon Analogue Risk-Task (BART), in a solo or peer condition, was used as a
proxy of real-life risk-taking. Results show a significant main effect of BART
condition. Post-hoc tests indicated higher risk-taking in the peer compared to
the solo condition in all groups except BD-only. Moreover, risk taking was
increased in adolescents with MBID compared to adolescents without MBID, but only
under peer-influence. No main or interaction effects with BD were observed. Model
based decomposition of BART performance in underlying processes showed that the
MBID related increase in risk-taking under peer-influence was mainly related to
increased risk-taking propensity, and in the MBID-only group also to increased
safety estimates and increased confidence in these safety estimates. The present
study shows that risk-taking in MBID may be better explained by low intellectual
functioning than by comorbid BD, and may not originate in increased risk taking
per se, but may rather be related to risk-taking under peer-influence, which is a
complex, multifaceted risk-taking context. Therefore, interventions to decrease
risk-taking by adolescents with MBID that specifically target peer-influence may
be successful.
PMID- 29946884
TI - Prognostic value of the combination of pre- and postoperative C-reactive protein
in colorectal cancer patients.
AB - PURPOSE: Inflammation is closely related to cancer development and progression.
This retrospective study investigated the prognostic value of the combination of
pre- and postoperative C-reactive protein (CRP) levels in patients with
colorectal cancer (CRC). METHODS: The subjects of this study were 406 patients
who underwent surgery for CRC. RESULTS: Based on receiver-operating
characteristic analysis, patients were divided into the following groups: those
with a preoperative CRP of >= 0.5 mg/dL (pre-CRPHigh), those with a preoperative
CRP of < 0.5 mg/dL (pre-CRPLow), those with a postoperative CRP of >= 17.0 mg/dL
(post-CRPHigh), and those with a postoperative CRP of < 17.0 mg/dL (post-CRPLow).
They were then allocated to one of the following three groups: Group A, comprised
of those in the pre-CRPHigh and post-CRPHigh groups; Group B, comprised of those
in either the pre-CRPHigh and post-CRPLow or pre-CRPLow and post-CRPHigh groups;
and Group C, comprised of those in the pre-CRPLow and post-CRPLow groups. The
disease-specific 5-year survival rates were 53.8%, 72.8%, and 87.2% in Groups A,
B, and C, respectively, and these differences were significant. Finally,
multivariate analysis revealed that the combination of pre- and postoperative CRP
levels was an independent prognostic indicator. CONCLUSIONS: The combination of
pre- and postoperative CRP was predictive of the prognosis of CRC patients.
PMID- 29946887
TI - Help me Feel Better! Ecological Momentary Assessment of Anxious Youths' Emotion
Regulation with Parents and Peers.
AB - Anxious youth often have trouble regulating negative affect (NA) and tend to over
rely on parents when faced with challenges. It is unclear how social interactions
with parents or peers actually helps or hinders anxious youths' success in
regulating NA. The aim of this study was to examine whether the success of
anxious youths' emotion regulation strategies differed according to social
context. We compared the effectiveness of co-ruminating, co-problem solving and
co-distracting with parents/peers for regulating anxious youth's NA in response
to stress in their daily lives. We also examined the benefit of attempting each
strategy socially vs. non-socially (e.g., co-ruminating vs. ruminating). One
hundred-seventeen youth (9-14) with a current diagnosis of Separation Anxiety
Disorder, Generalized Anxiety Disorder, and/or Social Phobia completed an
ecological momentary assessment (14 calls over 5 days), reporting on recent
stressors, their affective state, presence of others, and emotion regulation
strategies within the prior hour. Mixed linear models revealed that co
distracting was the most effective social strategy for reducing NA, but only for
boys. Co-rumination was the least effective social strategy for regulating NA.
Regarding social context, only co-distracting was more effective for regulating
NA over distracting alone, but only among anxious boys. Results suggest that co
rumination is an ineffective use of social support for regulating NA. Anxious
boys may benefit from social support by co-distracting with parents/peers, but
improper use may reflect avoidance and contribute to long-term anxiety
maintenance. Results extend research on gender differences in interpersonal
relationships and emotion regulation.
PMID- 29946889
TI - [Modern mapping technologies : Technical background and clinical use].
AB - Successful mapping and ablation of arrhythmias can be a challenging clinical
task. For many years, conventional pacing maneuvers and activation mapping were
the gold standard to identify underlying arrhythmia mechanisms in ablation
procedures. In the last decade, technology has dramatically improved. In parallel
to high-density automated mapping, cardiac imaging and image integration tools
are increasingly used to assess the arrhythmia substrate and identify reentrant
circuits. The aim of this review is to describe the technologies underlying these
new mapping systems and to discuss their possible role in providing new insights
into identification and visualization of arrhythmia mechanisms.
PMID- 29946888
TI - Controlling pre-osteoblastic cell adhesion and spreading on glycopolymer brushes
of variable film thickness.
AB - Controlling the cell behavior on biocompatible polymer surfaces is critical for
the development of suitable medical implant coatings as well as in anti-adhesive
applications. Synthetic glycopolymer brushes, based on sugar methacrylate
monomers have been reported as robust surfaces to resist protein adsorption and
cell adhesion. In this study, poly(D-gluconamidoethyl methacrylate) (PGAMA)
brushes of various chain lengths were synthesized directly from initiator
functionalized glass substrates using surface-initiated atom transfer radical
polymerization. The glycopolymer film thicknesses were determined by
ellipsometry, whereas the wettability and the morphology of the surfaces were
characterized by static water contact angle measurements and atomic force
microscopy, respectively. Stable, grafted films with thicknesses in the dry state
between 4 and 20 nm and of low roughness (~1 nm) were obtained by varying the
polymerization time. Cell experiments with MC3T3-E1 pre-osteoblasts cultured on
the PGAMA brushes were performed to examine the effect of film thickness on the
cell morphology, cytoskeleton organization and growth. The results revealed good
cell spreading and proliferation on PGAMA layers of low film thickness, whereas
cell adhesion was prevented on polymer films with thickness higher than ~10 nm,
indicating their potential use in medical implants and anti-adhesive surfaces,
respectively.
PMID- 29946890
TI - [Mapping and ablation of cardiac arrhythmias : Never forget where you are coming
from].
AB - With the rapid development of new mapping and imaging technologies as well as
catheter ablation technologies, it is increasingly important to understand the
basic concepts of conventional mapping and ablation of cardiac arrhythmias.
Prerequisite for successful ablation is the exact identification of the
tachycardia mechanism and subsequent localization of the origin or tachycardic
substrate. Only intracardiac electrograms provide decisive information regarding
activation time and signal morphology. In some arrhythmias, it is necessary to
supplement conventional mapping with so-called pace and/or entrainment mapping.
This article aims to discuss and demonstrate the fundamentals of intracardiac
mapping as it relates to the mapping and ablation of supraventricular and
ventricular arrhythmias based on representative clinical cases. Modern three
dimensional mapping methods make it possible to individually optimize established
ablation strategies with significantly better spatial resolution. The authors
aimed to demonstrate that intracardiac uni- and bipolar electrograms provide
essential information about timing and morphology guiding successful catheter
ablation. Furthermore, our article provides useful information about conventional
cardiac mapping techniques including activation mapping, pace mapping, and
individual substrate mapping.
PMID- 29946891
TI - [Epicardial VT ablation : In whom, when, how and why?]
AB - Ventricular tachycardia (VT) is a leading cause of cardiovascular death and
remains the main cause of sudden cardiac death. Implanted cardiac defibrillators
(ICD) improve survival but the recurrent ICD therapies, mostly ICD shocks, are
associated with an increased mortality and deleterious psychological effects. In
this regard and based on the results of multicenter studies, the current European
guidelines recommend early referral for catheter ablation. The ablation strategy
(isolated endocardial approach or combined epi-/endocardial) depends mostly on
the underlying myocardial disease. Thus, almost all patients with right
ventricular dysplasia and Chagas disease, the majority of those with dilative
cardiomyopathy, and some patients with ischemic cardiomyopathy (mostly posterior
wall infarction or large transmural anterior wall infarction) have an epicardial
scar as the underlying substrate for recurrent VT episodes. Thus, in this group
of patients, isolated endocardial VT ablation may be associated with an increased
VT recurrence and therefore an epicardial approach is also needed. Cardiac
imaging (cardio-CT/MRI with late enhancement[MRI LE]) can reliably identify the
distribution and characteristics of the myocardial scar and may be helpful in
planning the ablation strategy. When performed in highly specialized centers,
epicardial catheter ablation of VT leads to a significant reduction of recurrent
VT episodes compared to the endocardial VT ablation alone and with lower
complication rates.
PMID- 29946892
TI - The use of platelet-rich fibrin as a hemostatic material in oral soft tissues.
AB - The control of postoperative bleeding represents one of the main intercurrent
events associated with soft tissue surgical procedures in the oral cavity. In
this context, platelet-rich fibrin (PRF) membranes are materials with great
potential for optimizing soft tissue healing and induction of hemostasis. This
interventional case series describes the treatment of 10 patients with excisional
biopsy of benign oral cavity lesions, following a screening sequence at the
surgery clinic of a Brazilian dental school between the years of 2015 and 2017.
After treatment with PRF, patients presented mean time for postoperative
hemostasis of 10.3 +/- 2.5 s, requiring the average use of three membranes to
cover the surgical area. The results suggest that the use of platelet-rich fibrin
membranes may represent a feasible alternative hemostatic material for the
treatment of oral lesions.
PMID- 29946894
TI - Invited Commentary: Dual Coverage of the Inferior Pole with Conjoined Fascial
Flap and Acellular Dermal Matrix for Immediate One-Stage Breast Reconstruction
with a Prosthetic Implant.
PMID- 29946893
TI - [Planning target volume : Management of uncertainties, immobilization, image
guided and adaptive radiation therapy].
AB - CLINICAL/METHODICAL ISSUE: As a standard, today's radiation therapy is based on
CT images which are used for therapy planning. These images are obtained once
before therapy starts and serve as a basis to obtain the position and shape of
the target volume. As the patient has to be positioned anew for each fraction,
deviations of the tumor position relative to the radiation field but also
internal motion of the tumor may occur. These deviations lead to uncertainties,
which are taken into account by adding a safety margin around the clinical target
volume (CTV) to create the planning target volume (PTV). STANDARD RADIOLOGICAL
METHODS: As a standard today, CT-based treatment planning is used, where images
are obtained once prior to therapy. The information on tumor position and shape,
which is obtained from these images, is used throughout the whole cycle of
radiation therapy without any change. This cycle may last several weeks.
METHODICAL INNOVATIONS: By repeated imaging of the patient in the treatment
position prior to each fraction, the position of the tumor can be assessed and
corrected for each fraction. PERFORMANCE: A reduction of positioning uncertainty
may be used to reduce the safety margin. This leads to a decreased volume of
irradiated normal tissue. ACHIEVEMENTS: A reduced volume of irradiated normal
tissue leads to reduced side effects and provides the opportunity of increased
tumor control by dose escalation. PRACTICAL RECOMMENDATIONS: Before the PTV is
reduced, a detailed analysis of the uncertainties for the specific imaging method
and radiation technique must be performed.
PMID- 29946895
TI - The Dysmorphic Concern Questionnaire in the German General Population:
Psychometric Properties and Normative Data.
AB - BACKGROUND: The Dysmorphic Concern Questionnaire (DCQ) is a widely used screening
instrument assessing dysmorphic concerns ranging from a mild to an excessive
level. It is often used in the setting of plastic and aesthetic surgery. The
present study aimed at examining the psychometric properties of the DCQ in a
random general population sample. METHODS: A representative sample of the German
general population (N = 2053, aged between 18 and 65 years, 54% females)
completed the DCQ as well as questionnaires on depression and appearance
concerns. RESULTS: The DCQ showed a good internal consistency with Cronbach's
alpha = 0.81. Its one-factor model structure was confirmed. Normative data were
stratified according to gender and age. Women reported more dysmorphic concerns
than men, but also within females the DCQ scores differed between age classes.
Overall, 4.0% of the sample reported excessive dysmorphic concerns based on a
previously defined cutoff sum score >= 11. CONCLUSION: The DCQ is a valid and
reliable screening tool to identify individuals with excessive dysmorphic
concerns. Excessive concerns may indicate also the presence of body dysmorphic
disorder, but for verifying a final diagnosis the use of a structured clinical
interview is necessary. LEVEL OF EVIDENCE IV: This journal requires that authors
assign a level of evidence to each article. For a full description of these
evidence-based medicine ratings, please refer to the Table of Contents or the
online Instructions to Authors www.springer.com/00266 .
PMID- 29946897
TI - User-Guided Segmentation of Multi-modality Medical Imaging Datasets with ITK
SNAP.
AB - ITK-SNAP is an interactive software tool for manual and semi-automatic
segmentation of 3D medical images. This paper summarizes major new features added
to ITK-SNAP over the last decade. The main focus of the paper is on new features
that support semi-automatic segmentation of multi-modality imaging datasets, such
as MRI scans acquired using different contrast mechanisms (e.g., T1, T2, FLAIR).
The new functionality uses decision forest classifiers trained interactively by
the user to transform multiple input image volumes into a foreground/background
probability map; this map is then input as the data term to the active contour
evolution algorithm, which yields regularized surface representations of the
segmented objects of interest. The new functionality is evaluated in the context
of high-grade and low-grade glioma segmentation by three expert neuroradiogists
and a non-expert on a reference dataset from the MICCAI 2013 Multi-Modal Brain
Tumor Segmentation Challenge (BRATS). The accuracy of semi-automatic segmentation
is competitive with the top specialized brain tumor segmentation methods
evaluated in the BRATS challenge, with most results obtained in ITK-SNAP being
more accurate, relative to the BRATS reference manual segmentation, than the
second-best performer in the BRATS challenge; and all results being more accurate
than the fourth-best performer. Segmentation time is reduced over manual
segmentation by 2.5 and 5 times, depending on the rater. Additional experiments
in interactive placenta segmentation in 3D fetal ultrasound illustrate the
generalizability of the new functionality to a different problem domain.
PMID- 29946896
TI - Streptomyces dioscori sp. nov., a Novel Endophytic Actinobacterium Isolated from
Bulbil of Dioscorea bulbifera L.
AB - A novel endophytic actinobacterium strain, A217T, was isolated from the bulbil of
Dioscorea bulbifera L. Its taxonomic position was characterized using a
polyphasic study. Morphological and chemotaxonomic characteristics of strain
A217T were consistent with those of members of the genus Streptomyces: long
straight to flexuous spore chain; cellular components contained LL-diaminopimelic
acid, ribose, and small traces of glucose in whole-cell hydrolysates; MK-9(H6)
and MK-9(H8) as predominant menaquinones. The patterns of major fatty acids are
C16:0, anteiso-C15:0, C15:0, iso-C14:0, C16:1 omega7c, anteiso-C17:0, and iso
C17:1 omega5c. The polar lipids comprised diphosphatidylglycerol,
phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol mannoside,
and glycolipid, as well as two unidentified phospholipids, one unidentified
aminolipid, and one unidentified aminophospholipid. The DNA G + C content of
draft genome is 70.7 mol%. Analysis of the 16S rRNA gene sequence and
phylogenetic trees revealed that the isolate was most closely related to S.
aurantiacus JCM 4453T (99.0%), S. glomeroaurantiacus JCM 4677T (99.0%), and S.
tauricus JCM 4837T (98.8%). The DNA-DNA hybridization values between the strain
A217T and three reference strains ranged from 34.6% to 51.7%. On the basis of
phenotypic and genotypic differentiation from all tested strains, isolate A217T
is proposed to represent a novel species of the genus Streptomyces, named
Streptomyces dioscori sp. nov. The type strain is A217T (= CGMCC 4.7415T = JCM
32173T).
PMID- 29946898
TI - Study of melatonin-mediated effects on various hepatic inflammatory responses
stimulated by IL-6 in a new HepG2-on-a-chip platform.
AB - Hepatocytes exhibit diverse reactions upon stimulation with the interleukin IL-6,
mainly in the context of inflammation and energy metabolism. Melatonin has been
shown to exert pleiotropic protective actions, such as anti-inflammation and anti
oxidative stress on many cell- and organ-types. The key role of the liver to
maintain homeostasis and metabolic regulation prompted us to evaluate the direct
modification of IL-6-induced alterations in HepG2 cells in a chip by melatonin.
IL-6 administration was followed by the reduced expression and activity of MRP2,
a loss of CYP1A activity, and the decline of PXR expression. Other effects were
the induction of acute phase responses (reduced albumin production as well as
increased CRP and hepcidin expression) and lowered expression of CREB3L3. IL-6
affected also the mitochondrial membrane potential together with elevated
mitochondrial superoxide generation, and glycogen deposition was reduced.
Melatonin counteracted all observed IL-6-induced alterations except the rise in
CRP release and CYP1A activity. Altogether, this new in vitro model can be
applied to investigate hepatic inflammatory responses stimulated by IL-6, and
these results indicate that hepatocellular inflammatory responses to IL-6 are
mitigated by melatonin.
PMID- 29946899
TI - Role of contact force in ischemic scar-related ventricular tachycardia ablation;
optimal force required and impact of left ventricular access route.
AB - BACKGROUND: Contact force-sensing technology has become a widely used addition to
catheter ablation procedures. Neither the optimal contact force required to
achieve adequate lesion formation in the ventricle, nor the impact of left
ventricular access route on contact force has been fully clarified. PATIENTS AND
METHODS: Consecutive patients (n = 24) with ischemic cardiomyopathy who underwent
ablation for scar-related ventricular tachycardia were included in the study. All
ablations (n = 25) were performed using irrigated contact force-sensing catheters
(Smart Touch, Biosense Webster). Effective lesion formation was defined as
electrical unexcitability post ablation at sites which were electrically
excitable prior to ablation (unipolar pacing at 10 mA, 2 ms pulse width). We
explored the contact force which achieved effective lesion formation and the
impact of left ventricular access route (retrograde aortic or transseptal) on the
contact force achieved in various segments of the left ventricle. Scar zone was
defined as bipolar signal amplitude < 0.5 mV. RESULTS: Among 427 ablation points,
effective lesion formation was achieved at 201 points (47.1%). Contact force did
not predict effective lesion formation in the overall group. However, within the
scar zone, mean contact force >= 10 g was significantly associated with effective
lesion formation [OR 3.21 (1.43, 7.19) P = 0.005]. In the 12-segment model of the
left ventricle, the retrograde approach was associated with higher median contact
force in the apical anterior segment (31 vs 19 g; P = 0.045) while transseptal
approach had higher median force in the basal inferior segment (25 vs 15 g; P =
0.021). In the 4-segment model, the retrograde approach had higher force in the
anterior wall (28 vs 16 g; P = 0.004) while the transseptal approach had higher
force in the lateral wall (21 vs 18 g; P = 0.032). There was a trend towards
higher force in the inferior wall with the transseptal approach, but this was not
statistically significant (20 vs 15 g; P = 0.063). CONCLUSIONS: In patients with
ischemic cardiomyopathy, a mean contact force of 10 g or more within the scar
zone had the best correlation with electrical unexcitability post ablation in our
study. The retrograde aortic approach was associated with better contact force
over the anterior wall while use of a transseptal approach had better contact
force over the lateral wall.
PMID- 29946900
TI - Appeal to the Rule of Rescue in health care: discriminating and not benevolent?
AB - Thirty years of debate have passed since the term "Rule of Rescue" has been
introduced into medical ethics. Its main focus was on whether or why medical
treatment for acute conditions should have priority over preventive measures
irrespective of opportunity costs. Recent contributions, taking account of the
widespread reluctance to accept purely efficiency-oriented prioritization
approaches, advance another objection: Prioritizing treatment, they hold,
discriminates against statistical lives. The reference to opportunity costs has
also been renewed in a distinctly ethical fashion: It has been stipulated that
favoring help for identifiable lives amounts to a lack of benevolence for one's
fellow creatures. The present article argues against both objections. It suggests
that the debate's focus on consequences (deaths or severe ill health) should be
reoriented by asking which aspects of such states of affairs are actually
attributable to a decision maker who judges within a specific situation of
choice.
PMID- 29946901
TI - Correlation Between Physicochemical Properties of Soil and Presence of
Leptospira.
AB - Leptospirosis is an important global public health problem. Favourable
environmental factors are influencing the survival of leptospires in soil, which
is an important link in the transmission cycle. The present study was designed to
understand the correlation between various soil nutrients and presence of
Leptospira in soil samples of different regions of Andaman and Nicobar Islands.
The study revealed a significant positive relationship between presence of
Leptospira and concentration of iron, manganese and copper in soil. Presence of
iron, manganese and copper in the soil may influence the survival and
transmission of leptospirosis.
PMID- 29946902
TI - Different glaucoma types and glaucoma surgeries among different age groups.
PMID- 29946904
TI - CaHSP16.4, a small heat shock protein gene in pepper, is involved in heat and
drought tolerance.
AB - Environmental stress affects growth and development of crops, and reduces yield
and quality of crops. To cope with environmental stressors, plants have
sophisticated defense mechanisms, including the HSF/HSP pathway. Here, we
identify the expression pattern of CaHSP16.4 in thermo-tolerant and thermo
sensitive pepper (Capsicum annuum L.) lines. Under heat stress, R9 thermo
tolerant line had higher CaHSP16.4 expression level than the B6 thermo-sensitive
line. Under drought stress, expression pattern of CaHSP16.4 was dynamic.
Initially, CaHSP16.4 was downregulated then CaHSP16.4 significantly increased.
Subcellular localization assay showed that CaHSP16.4 localizes in cytoplasm and
nucleus. In the R9 line, silencing of CaHSP16.4 resulted in a significant
increase in malonaldehyde content and a significant reduction in total
chlorophyll content, suggesting that silencing of CaHSP16.4 reduces heat and
drought stresses tolerance. Overexpression of CaHSP16.4 enhances tolerance to
heat stress in Arabidopsis. Under heat stress, the survival rate of CaHSP16.4
overexpression lines was significantly higher than wild type. Furthermore, under
heat, drought, and combined stress conditions, the CaHSP16.4-overexpression lines
had lower relative electrolytic leakage and malonaldehyde content, higher total
chlorophyll content, and higher activity levels of superoxide dismutase,
catalase, ascorbic acid peroxidase, and glutathione peroxidase compared to wild
type. Furthermore, the expression levels of the stress response genes in the
overexpression lines were higher than the wild type. These results indicate that
the overexpression of CaHSP16.4 enhances the ability of reactive oxygen species
scavenging under heat and drought stress.
PMID- 29946903
TI - Inactivation of MAPK in epididymal fat and amelioration of triglyceride secretion
by injection of GRK2 siRNA in ob/ob mice.
AB - Abnormal G protein-coupled receptor kinase 2 (GRK2) accumulation has a crucial
role in the development of insulin resistance and diabetes. Although GRK2 siRNA
transfection in the liver improves insulin resistance-related vascular
complications, the effects of GRK2 siRNA in lipid metabolism and obesity remain
unknown. To investigate how GRK2 siRNA affects obesity, ob/ob mice were
transfected with GRK2 siRNA, mainly in the liver, by using a hydrodynamic-based
procedure. Epididymal fat, glucose, triglyceride, non-esterified fatty acid
(NEFA), and alanine transaminase activity were higher in the control siRNA
transfected ob/ob mice than in the control siRNA-transfected Lean mice, but these
parameters were reduced by GRK2 siRNA transfection into the ob/ob mice. GRK2
expression in epididymal fat was not altered among the 3 groups, although hepatic
GRK2 expression was higher in the control siRNA-transfected ob/ob mice than in
the control siRNA-transfected Lean mice. Additionally, we found that Akt
interacted with GRK2 in the liver. Furthermore, phosphorylation levels of ERK1/2
and JNK were higher in the epididymal fats from the control siRNA-transfected
ob/ob mice than in those from the control siRNA-transfected Lean mice, but they
were lowered by transfection with GRK2 siRNA. The study results showed that GRK2
siRNA improved blood triglyceride levels and abnormal or excessive activity of
mitogen-activated protein kinases in epididymal fat. This effect may be promoted
by inhibition of the NEFA production pathway in the liver. Therefore, the
interaction of organs (hepatic GRK2-epididymal fat) may help improve insulin
resistance and diabetes-associated pathophysiology.
PMID- 29946905
TI - Formation pattern in five types of pollen tetrad in Pseuduvaria trimera
(Annonaceae).
AB - In basal angiosperms, there are several types of permanent tetrad but their
formation pattern remains elusive. Pseuduvaria trimera has five types of tetrads
and is the species with the most abundant tetrad types in Annonaceae. In order to
interpret the formation pattern of different tetrad types, pollen development was
investigated from the microspore mother cell stage to the bicellular pollen stage
and the ultrastructure of pollen wall in the five tetrad types using light
microscopy, transmission electron microscopy, and confocal laser scanning
microscopy. Both successive and intermediate cytokinesis were observed within the
same anther. The nucleus location of the microspores together with cytokinesis
determine the number and the spatial arrangement of callose plates, and further
have an effect on the tetrad types. The anthers with or without septation and the
arrangement of microsporocytes might be also related to the tetrad type. The
individual pollen grains within the tetrads are connected with each other by
crosswall cohesion and cytoplasmic channels at localized points in the proximal
walls. The various types of tetrads, cytokinesis, and cohesion in P. trimera
reflect the high diversity in pollen development, which enhances the dramatic
variety in pollen morphology in this family. Our observations of the development
of tetrads provided some new insights for interpreting the factors influencing
the types of tetrads, and reported the existence of a cytoplasmic channel in
Annonaceae for the first time.
PMID- 29946906
TI - Effects of post-remission chemotherapy before allo-HSCT for acute myeloid
leukemia during first complete remission: a meta-analysis.
AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is most frequently
used to treat acute myeloid leukemia (AML). Whether patients should routinely
receive consolidation chemotherapy before proceeding to transplant after
achieving first complete remission (CR1) has been a subject of debate. We
performed a systematic review and meta-analysis of studies examining the impact
of post-remission chemotherapy before allo-HSCT in patients with AML in CR1. Six
studies including 1659 patients were included in the meta-analysis. The pooled
hazard ratio (HR) for overall survival was 0.9 (95% confidence interval [CI] 0.77
1.05, P = 0.182), and the pooled HR for leukemia-free survival was 0.87 (95% CI
0.75-1.0, P = 0.07). No survival advantage was observed for post-remission
chemotherapy before reduced-intensity conditioning or myeloablative conditioning
(MAC) allo-HSCT for AML in CR1. The pooled relative risk for relapse incidence
(RI) was 1.02 (95% CI 0.82-1.28, P = 0.834). Post-remission chemotherapy before
allo-HSCT did not significantly affect the RI in patients with AML in CR1. The
analyses revealed no significant benefit of post-remission consolidation
chemotherapy in patients who received allo-HSCT. We recommend proceeding to allo
HSCT as soon as CR1 is attained.
PMID- 29946907
TI - High chymotrypsin-like activity in the plasma of patients with newly diagnosed
multiple myeloma treated with bortezomib is predictive of a better response and
longer PFS.
AB - Proteasome inhibitors (PIs) such as bortezomib constitute an important part of
the modern standard therapy for multiple myeloma (MM). In this study, we set out
to assess whether proteasome concentration and chymotrypsin-like (ChT-L) activity
could serve as potential biomarkers defining the likelihood of response to
treatment with bortezomib, in order to identify patients who are more likely to
respond to treatment with PI. We analysed proteasome concentration and ChT-L
activity in the plasma of 78 patients with newly diagnosed MM during treatment
with or without proteasome inhibitors. Values of all the studied parameters in
the group of responders decreased sharply from the initial levels already after
the third cycle of chemotherapy and remained significantly lower until the end of
treatment. On the other hand, in the group of non-responders, there was an
increase in the measured proteasome parameters already after the third cycle, and
they remained high during the next cycles of therapy. We also showed that high
baseline proteasome ChT-L activity values might prognosticate longer progression
free survival (PFS) in patients treated with PI. Our findings demonstrate that
measuring plasma proteasome ChT-L activity can be used as a powerful biomarker
for predicting clinical response to treatment and PFS in patients with newly
diagnosed MM.
PMID- 29946908
TI - gammadelta T cell clonal proliferation early after PD-1 blockade.
PMID- 29946910
TI - Risk of viral reactivation in patients with occult hepatitis B virus infection
during ruxolitinib treatment.
PMID- 29946909
TI - Impact of age and comorbidities on the efficacy of FC and FCR regimens in chronic
lymphocytic leukemia.
AB - CLL is an aging-associated neoplasm with median age at diagnosis > 65 years.
Little is known about safety and efficacy of FC/FCR regimens in elderly CLL
patients with multiple comorbidities. We retrospectively revised medical records
of 90 patients treated with FC/FCR regimens in our clinic. Data on demographic
and biological characteristics, comorbidities, response to therapy, and treatment
associated adverse events were analyzed. Compared to FC, FCR yielded higher rates
of OR (93.6 vs. 81.4%, p = .109) and CR (72.3 vs. 46.5%, p = .018). This
translated in longer EFS (median 52 vs. 19 months, p = <.001) and OS (median 89
vs. 45 months, p = .001). Elderly patients (>= 65 years) had more comorbidities
and higher median CIRS-G score (7 vs. 4, p < .001). However, no association was
found between CIRS-G score and survival. Decreased renal function was associated
with dismal prognosis in patients treated with FCR.
PMID- 29946911
TI - Features of vascular adverse events in Japanese patients with chronic myeloid
leukemia treated with tyrosine kinase inhibitors: a retrospective study of the
CML Cooperative Study Group database.
AB - This study investigated the incidence rate and features of vascular adverse
events (VAEs) in Japanese patients with chronic myeloid leukemia (CML) who were
treated with tyrosine kinase inhibitors (TKIs). The analysis included 369 CML
patients in the chronic or accelerated phases, selected from the CML Cooperative
Study Group database; 25 events in 23 (6.2%) of these patients were VAEs. At the
time of VAE incidence, nine patients were on treatment with imatinib, 12 with
nilotinib, three with dasatinib, and one with bosutinib. VAE incidence comprised
13 cases of ischemic heart disease (IHD), eight of cerebral infarction (CI), and
four of peripheral arterial occlusive disease (PAOD). IHD incidence rate in the
study population was higher than that in the age-matched general population,
particularly in nilotinib-treated patients, while CI incidence rate was almost
equivalent. Compared with the Suita score, the SCORE chart and the Framingham
score risk assessment tools detected more patients with high or very high risk of
VAEs. In conclusion, incidence of IHD requires closer monitoring in nilotinib
treated patients. More detailed investigations for determining the most useful
tool to predict VAE incidence and long-term analysis of therapy-related VAE cases
are needed for improving safety during TKI therapy.
PMID- 29946912
TI - Correction to: The association of venous thromboembolism with survival in
pediatric cancer patients: a population-based cohort study.
AB - The Figure 1 used in the originally published version of this article was
incorrect.
PMID- 29946913
TI - Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of
Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology
Setting.
AB - BACKGROUND: The combination chemotherapy regimens of nab-paclitaxel plus
gemcitabine (nab-p + G) and FOLFIRINOX (FFX) have each demonstrated improved
survival compared with gemcitabine monotherapy in clinical trials for metastatic
pancreatic cancer; however, limited comparative data exist. OBJECTIVE: The
objective of this study was to compare patient characteristics and clinical
outcomes including time to treatment failure and overall survival in patients
with metastatic pancreatic cancer receiving first-line chemotherapy in the
community. METHODS: We conducted a retrospective, multi-site, observational
cohort study of patients with metastatic pancreatic cancer receiving first-line
nab-p + G, FFX, or gemcitabine monotherapy between April 2013 and October 2015,
using data from the iKnowMed electronic health record database. Patients on
clinical trials or with other cancer diagnoses were excluded. Time to treatment
failure and overall survival were assessed by Kaplan-Meier methods. RESULTS: Four
hundred and eighty-six patients met selection criteria, 255 nab-p + G, 159 FFX,
and 72 gemcitabine patients. Median age was 61, 68, and 73 years for FFX, nab-p +
G, and gemcitabine patients, respectively (p < 0.01 for nab-p + G vs. FFX).
Eastern Cooperative Oncology Group performance status of 0-1 was 91% for FFX, 77%
for nab-p + G, and 68% for gemcitabine patients (p < 0.01 for nab-p + G vs. FFX).
For the nab-p + G vs. FFX cohorts, respectively, time to treatment failure was
3.7 vs. 4.3 months (log-rank p = 0.25); and OS was 9.8 vs. 11.4 months (log-rank
p = 0.38). Among patients with Eastern Cooperative Oncology Group performance
status 0-1, time to treatment failure was 4.2 vs. 4.3 months (log-rank p = 0.47);
and overall survival was 12.1 vs 11.4 months (log-rank p = 0.68). CONCLUSIONS:
The nab-p + G patients were older and had worse performance status than FFX
patients. Time to treatment failure and overall survival were not observed to be
significantly different in first-line nab-p + G and FFX patients. Results were
similar after stratifying by performance status.
PMID- 29946914
TI - Constructing Sound and Reliable Ethical Guidelines for Prevention Science.
PMID- 29946915
TI - Therapeutic and Protective Potency of Bee Pollen Against Neurotoxic Effects
Induced by Prenatal Exposure of Rats to Methyl Mercury.
AB - MeHg is a widely distributed environmental toxicant with harmful effects on the
developing and adult nervous system. This study aimed to evaluate the therapeutic
and protective efficacy of pollen grain in improving the toxic effects of MeHg,
through the measurement of selected biochemical parameters linked to oxidative
stress, energy metabolism, and neurotransmission in brain homogenates of male
pups' neonates. Forty healthy pregnant female rats were randomly divided into
five groups, and after delivery, each group was consisting of 10 male neonates:
(1) neonates delivered by control mothers, (2) neonates delivered by bee pollen
treated mothers who received bee pollen at the dose of 200-mg/kg body weight from
postnatal day 0 for 4 weeks, (3) neonates delivered by MeHg-treated mothers who
received MeHg at the dose of 0.5 mg/kg/day via drinking water from gestational
day 7 till postnatal day 7 of delivery, (4) therapeutic group: neonates delivered
by MeHg-treated mothers followed by bee pollen treatment who received bee pollen
at the dose of 200-mg/kg body weight from postnatal day 0 for 4 weeks, and (5)
protective group: neonates delivered by MeHg and bee pollen-treated mothers.
Mothers continued receiving the bee pollen at the same dose until day 21.
Biochemical parameters linked to oxidative stress and energy metabolism and
neurotransmission were investigated in brain homogenates of neonates from all the
five groups. MeHg treatment showed an increase in oxidative stress markers like
lipid peroxidation and catalase activity coupled with a non-significant decrease
in glutathione level. Impaired energy metabolism was ascertained via the
inhibition of creatine kinase and lactate dehydrogenase activities. Dramatic
decrease of Mg2+ and K+ concentrations confirmed the neurotransmission defect.
Interestingly, the bee pollen treatment was highly effective in restoring the
catalase, lactate dehydrogenase, and creatine kinase activities in addition to
normalizing the levels of Mg2+, K+, lipid peroxidation, and glutathione. Overall,
the exposure to MeHg during the developing brain stages was highly effective to
show signs and symptoms of neuronal toxicity. Furthermore, it has been concluded
that bee pollen can be used safely to ameliorate oxidative stress, poor
detoxification as well as metal ion defects, and neuronal death as a critical
mechanisms involved in the etiology of numerous neurological disorders.
PMID- 29946916
TI - Monitoring and assessment of groundwater quality in a khondalitic terrain, Andhra
Pradesh, India.
AB - The groundwater quality assessment for the drinking and irrigation purpose is
carried out in the Kandivalasa River Sub Basin covered with khondalitic suite
(Garneti ferrous, Sillimanite, Gneiss) of rocks, near Cheepurupalli town of
Vizianagaram district, Andhra Pradesh, India. The analysis for the groundwater
quality for drinking has shown the slightly alkaline nature and high values of
alkalinity in the study area. A very high concentration of total dissolved solids
value is observed at one pocket where there has been contamination by many
fertilizer industries located nearby the study area. The groundwater is highly
affected by the nitrate. Higher fluoride values are obtained at few pockets. Most
of the samples in the study area are categorized as very hard category. According
to the Piper trilinear diagram, it can be observed that the carbonate hardness
and secondary salinity have occupied at major part of study area. From the
analysis of sodium adsorption ratio, salinity hazard, sodium percentage, residual
sodium carbonate, and Kelly's ratio, all the groundwater samples except at few
locations fell under the category of good to excellent for irrigation. The
prepared integrated groundwater quality maps for the drinking purpose and
agricultural purposes are indicating that, by and large, the low-lying areas are
having poor groundwater quality than the uplands for drinking as well as
agricultural needs which means that the groundwater quality of the basin is
following the topography.
PMID- 29946917
TI - A multicentre investigation of organ and tissue donation education for critical
care residents.
AB - PURPOSE: To describe critical care medicine residents' training, expertise, and
skills regarding organ and tissue donation processes and procedures. METHODS: We
undertook a qualitative multicentre study and employed a purposive sample of
program directors, physicians, nurses, residents, and organ donation leaders from
all nine academic intensive care unit (ICU) training centres (five adult, four
pediatric) in Ontario (n = 71). Interviews, conducted by telephone between
December 2015 and March 2016, were audio-recorded and transcribed verbatim. Data
collection and analysis were performed using an iterative process and continued
until saturation was achieved. RESULTS: Five main themes were identified: 1) gaps
in residents' knowledge for both neurologic determination of death (NDD) and
circulatory determination of death (DCD) cases; 2) commitment to the provision of
organ and tissue donation training; 3) limited experiential learning (NDD and
DCD); 4) challenges related to the provision of training on organ donation and
need for a standardized curriculum; and 5) communication with family members.
Overall, this study showed system-level gaps in training resulting from the lack
of a standardized provincial curriculum on organ donation. CONCLUSIONS:
Qualitative data corroborated that residents need more exposure to clinical
cases, especially regarding DCD donors. A standardized education curriculum would
be beneficial for all residents within the ICU. Developing a better shared
understanding of the donation process will improve team communication and
performance, translate into a better end-of-life experience for families, and
potentially result in increased donation rates.
PMID- 29946918
TI - Top Down or Bottom Up? Longitudinal assessment of the influence of professional
practice gaps in gastrointestinal and endoscopic surgery on program content for
the Annual Meeting of the Society of American Gastrointestinal and Endoscopic
Surgeons (SAGES) (2011-2016): a report from the SAGES Continuing Education
Committee (CEC).
PMID- 29946919
TI - With widespread adoption of MIS colectomy for colon cancer, does hospital type
matter?
AB - BACKGROUND: Recent studies have shown that hospital type impacts patient
outcomes, but no studies have examined hospital differences in outcomes for
patients undergoing minimally invasive surgery (MIS) for segmental colectomies.
METHODS: The 2010-2014 National Cancer Data Base was queried for patients
undergoing segmental colectomy for non-metastatic colon adenocarcinoma.
Descriptive statistics characterized MIS utilization by hospital type.
Multivariable models were used to examine the effect of hospital type on outcomes
after MIS. Survival probability was plotted using the Kaplan-Meier method.
RESULTS: 80,922 patients underwent MIS segmental colectomy for colon cancer from
2010 to 2014. From 2010 to 2014, the number of MIS segmental colectomies
increased by 157% at academic hospitals, 151% at comprehensive hospitals, and
153% at community hospitals. Compared to academic hospitals, community and
comprehensive hospitals had greater adjusted odds of positive margins (Community
OR 1.525, 95% Confidence Interval 1.233-1.885; Comprehensive OR 1.216, 95% CI
1.041-1.42), incomplete number of lymph nodes analyzed (< 12 LNs) from surgery
(Community OR 2.15, 95% CI 1.98-2.32; Comprehensive OR 1.42, 95% CI 1.34-1.51),
and greater 30-day mortality (Community OR 1.43, 95% CI 1.14-1.78; Comprehensive
OR 1.36, 95% CI 1.17-1.59). Patient survival probability was higher at academic
hospitals at 5 years (Academic 69% vs. Comprehensive 66% vs. Community 63%, p <
0.001). Community hospitals and comprehensive hospitals had significantly higher
risk of adjusted long-term mortality (Community HR 1.28; 95% CI 1.19-1.37; p <
0.001; Comprehensive HR 1.14; 95% CI 1.09-1.20; p < 0.001). CONCLUSIONS: Despite
widespread use of laparoscopic oncologic surgery, short- and long-term outcomes
from MIS for segmental colectomy are superior at academic hospitals. This
difference may be due to superior perioperative oncologic technique and surgical
outcomes at academic hospitals. Our data provide important information for
patients, referring physicians, and surgeons about the significance of hospital
type in management of colon cancer.
PMID- 29946920
TI - Systematic Review of Biofeedback Interventions for Addressing Anxiety and
Depression in Children and Adolescents with Long-Term Physical Conditions.
AB - Children and adolescents with long-term physical conditions are at increased risk
of psychological problems, particularly anxiety and depression, and they have
limited access to evidence-based treatment for these issues. Biofeedback
interventions may be useful for treating symptoms of both psychological and
physical conditions. A systematic review of studies of biofeedback interventions
that addressed anxiety or depression in this population was undertaken via
MEDLINE, EMBASE, PsycINFO, CINAHL and the Cochrane Central Register of Controlled
Trials databases. Primary outcomes included changes in anxiety and depression
symptoms and 'caseness'. Secondary outcomes included changes in symptoms of the
associated physical condition and acceptability of the biofeedback intervention.
Of 1876 identified citations, 9 studies (4 RCTs, 5 non-RCTs; of which all
measured changes in anxiety and 3 of which measured changes in depression) were
included in the final analysis and involved participants aged 8-25 years with a
range of long-term physical conditions. Due to the heterogeneity of study design
and reporting, risk of bias was judged as unclear for all studies and meta
analysis of findings was not undertaken. Within the identified sample, multiple
modalities of biofeedback including heart rate variability (HRV), biofeedback
assisted relaxation therapy and electroencephalography were found to be effective
in reducing symptoms of anxiety. HRV was also found to be effective in reducing
symptoms of depression in two studies. A range of modalities was effective in
improving symptoms of long-term physical conditions. Two studies that assessed
acceptability provided generally positive feedback. There is currently limited
evidence to support the use of biofeedback interventions for addressing anxiety
and depression in children and adolescents with long-term physical conditions.
Although promising, further research using more stringent methodology and
reporting is required before biofeedback interventions can be recommended for
clinical use instead or in addition to existing evidence-based modalities of
treatment.
PMID- 29946921
TI - Model-Informed Approaches for Alternative Aripiprazole Dosing Regimens and Missed
Dose Management: Towards Better Adherence to Antipsychotic Pharmacotherapy.
PMID- 29946922
TI - A model of motor and sensory axon activation in the median nerve using surface
electrical stimulation.
AB - Surface electrical stimulation has the potential to be a powerful and non
invasive treatment for a variety of medical conditions but currently it is
difficult to obtain consistent evoked responses. A viable clinical system must be
able to adapt to variations in individuals to produce repeatable results. To more
fully study the effect of these variations without performing exhaustive testing
on human subjects, a system of computer models was created to predict motor and
sensory axon activation in the median nerve due to surface electrical stimulation
at the elbow. An anatomically-based finite element model of the arm was built to
accurately predict voltages resulting from surface electrical stimulation. In
addition, two axon models were developed based on previously published models to
incorporate physiological differences between sensory and motor axons. This
resulted in axon models that could reproduce experimental results for conduction
velocity, strength-duration curves and activation threshold. Differences in
experimentally obtained action potential shape between the motor and sensory
axons were reflected in the models. The models predicted a lower threshold for
sensory axons than motor axons of the same diameter, allowing a range of sensory
axons to be activated before any motor axons. This system of models will be a
useful tool for development of surface electrical stimulation as a method to
target specific neural functions.
PMID- 29946923
TI - Validation of a DIXON-based fat quantification technique for the measurement of
visceral fat using a CT-based reference standard.
AB - PURPOSE: The purpose of the study is to determine whether a novel semi-automated
DIXON-based fat quantification algorithm can reliably quantify visceral fat using
a CT-based reference standard. METHODS: This was an IRB-approved retrospective
cohort study of 27 subjects who underwent abdominopelvic CT within 7 days of
proton density fat fraction (PDFF) mapping on a 1.5T MRI. Cross-sectional
visceral fat area per slice (cm2) was measured in blinded fashion in each
modality at intervertebral disc levels from T12 to L4. CT estimates were obtained
using a previously published semi-automated computational image processing system
that sums pixels with attenuation - 205 to - 51 HU. MR estimates were obtained
using two novel semi-automated DIXON-based fat quantification algorithms that
measure visceral fat area by spatially regularizing non-uniform fat-only signal
intensity or de-speckling PDFF 2D images and summing pixels with PDFF >= 50%.
Pearson's correlations and Bland-Altman analyses were performed. RESULTS:
Visceral fat area per slice ranged from 9.2 to 429.8 cm2 for MR and from 1.6 to
405.5 cm2 for CT. There was a strong correlation between CT and MR methods in
measured visceral fat area across all studied vertebral body levels (r = 0.97; n
= 101 observations); the least (r = 0.93) correlation was at T12. Bland-Altman
analysis revealed a bias of 31.7 cm2 (95% CI [- 27.1]-90.4 cm2), indicating
modestly higher visceral fat assessed by MR. CONCLUSION: MR- and CT-based
visceral fat quantification are highly correlated and have good cross-modality
reliability, indicating that visceral fat quantification by either method can
yield a stable and reliable biomarker.
PMID- 29946924
TI - Winslow's pathway.
PMID- 29946925
TI - Clear cell renal cell carcinoma: identifying PTEN expression on multiphasic MDCT.
AB - PURPOSE: To investigate whether multiphasic MDCT enhancement profiles can help to
identify PTEN expression in clear cell renal cell carcinomas (ccRCCs). Lack of
PTEN expression is associated with worsened overall survival, a more advanced
Fuhrman grade, and a greater likelihood of lymph mode metastasis. METHODS: With
IRB approval for this retrospective study, we derived a cohort of 103
histologically proven ccRCCs with preoperative 4-phase renal mass MDCT from 2001
2013. Following manual segmentation, a computer-assisted detection algorithm
selected a 0.5-cm-diameter region of maximal attenuation within each lesion in
each phase; a 0.5-cm-diameter region of interest was manually placed on
uninvolved renal cortex in each phase. The relative attenuation of each lesion
was calculated as [(Maximal lesion attenuation - cortex attenuation)/cortex
attenuation] * 100. Absolute and relative attenuation in each phase were compared
using t tests. The performance of multiphasic enhancement in identifying PTEN
expression was assessed with logistic regression analysis. RESULTS: PTEN-positive
and PTEN-negative ccRCCs both exhibited peak enhancement in the corticomedullary
phase. Relative corticomedullary phase attenuation was significantly greater for
PTEN-negative ccRCCs in comparison to PTEN-positive ccRCCs (33.7 vs. 9.5, p =
0.03). After controlling for lesion stage and size, relative corticomedullary
phase attenuation had an accuracy of 84% (86/103), specificity of 100% (84/84),
sensitivity of 11% (2/19), positive predictive value of 100% (2/2), and negative
predictive value of 83% (84/101) in identifying PTEN expression. CONCLUSION:
Relative corticomedullary phase attenuation may help to identify PTEN expression
in ccRCCs, if validated prospectively.
PMID- 29946926
TI - The interface sign.
PMID- 29946927
TI - A case of laparoscopic high anterior resection of rectosigmoid colon cancer
associated with a horseshoe kidney using preoperative 3D-CT angiography.
AB - BACKGROUND: Horseshoe kidney is a congenital malformation in which the bilateral
kidneys are fused. It is frequently complicated by other congenital malformations
and is often accompanied by anomalies of the ureteropelvic and vascular systems,
which must be evaluated to avoid iatrogenic injury. We report a case of
laparoscopic high anterior resection of rectosigmoid colon cancer associated with
a horseshoe kidney using preoperative 3D-CT angiography. CASE PRESENTATION: A 52
year-old Japanese man with lower abdominal pain underwent lower endoscopy,
revealing a type 2 lesion in the rectosigmoid colon. He was diagnosed with
rectosigmoid colon cancer with multiple lung metastases and a horseshoe kidney on
computed tomography (CT) scan. Three-dimensional (3D)-CT angiography showed an
aberrant renal artery at the isthmus from 3 cm under the inferior mesenteric
artery (IMA) branch of the aorta. Laparoscopic anterior rectal resection was
performed. During the operation, the inferior mesenteric artery, left ureter,
left gonadal vessels, and hypogastric nerve plexus could be seen passing over the
horseshoe kidney isthmus and were preserved. The left branch of aberrant renal
artery that was close to IMA was also detected and preserved. CONCLUSION: To
prevent intraoperative misidentification, 3D-CT angiography should be performed
preoperatively to ascertain the precise positional relationships between the
extra renal arteries and the kidney. We always must consider anomalous locations
of renal vessels, ureter, gonadal vessels, and lumbar splanchnic nerve to avoid
laparoscopic iatrogenic injury in patients with a horseshoe kidney.
PMID- 29946928
TI - Study of rheological properties of acai berry pulp: an analysis of its time
dependent behavior and the effect of temperature.
AB - The industry of acai-based products has been growing in the last few years.
Knowledge about the physical properties of acai pulp, including its rheology, is
essential to the optimization of industrial processes. This work presents the
rheological behavior of acai berry pulp in relation to the effects of shear rate,
temperature, and time of shearing. The entire study was carried out in the
temperature range of 10-70 degrees C. Acai pulp showed a non-Newtonian,
pseudoplastic, and time-dependent behavior. Four upward and backward shear rate
cycles were evaluated, resulting in complex hysteresis loops, in which thixotropy
and anti-thixotropy zones were observed. Downward flow curves could be
satisfactorily represented by the Power-Law rheological model. The stress
profiles as a function of shear rate obtained in the first upward curves suggest
a breakdown of the initial fluid structure at low shear rates. Tests were also
carried out at a constant shear rate of 20 s-1 and, in this case, the Weltman
model of thixotropy satisfactorily fit the experimental data. The activation
energy, which was calculated by the Arrhenius equation, was 29.0 kJ/mol. The
achievements of this work may be useful to further studies about acai pulp
rheology and may contribute to process design in the acai industry.
PMID- 29946929
TI - Comparing incobotulinumtoxinA (Xeomin(r)) and onabotulinumtoxinA (Botox(r)):
identical potency labelling in the hemidiaphragm assay.
AB - Botulinum toxin (BT) is provided by several manufacturers producing a number of
different drugs. Their potency is given in internationally standardised mouse
units (MU). Clinical practise, however, reveals that the potency labelling of
different BT drugs may not be identical. We wanted to use the mouse diaphragm
assay (MDA) to compare the two BT drugs onabotulinumtoxinA (ONA) and
incobotulinumtoxinA (INCO). For this, we measured the paresis time (PT) of
different ONA or INCO doses. All BT came from several different and unexpired
drug batches. PT for 20MU were 169.7 +/- 28.9 min (ONA) and 132.3 +/- 1.5 min
(INCO) (p = 0.089), for 60MU 105.3 +/- 10.1 min and 84.7 +/- 4.2 min (p = 0.031),
for 100MU 69.7 +/- 1.5 min and 66.0 +/- 7.0 min (p = 0.462) and for 140MU 74.7 +/
0.6 min and 62.3 +/- 2.1 min (p = 0.100), respectively. The overall PT were
104.8 +/- 12.5 and 86.3 +/- 8.5 min (p = 0.178). Results presented here do not
reveal differences in potency labelling between ONA and INCO, even when the full
range of therapeutic doses are examined, although there was a trend towards
stronger INCO effects. Data confirm previous reports on identical potency
labelling of ONA and INCO. The MDA seems to be an appropriate instrument to test
the potency labelling of other BT drugs as well, including new BT drugs currently
under development.
PMID- 29946930
TI - Optimizing the coordinated transcription of central xylose-metabolism genes in
Saccharomyces cerevisiae.
AB - The efficient fermentation of xylose can improve biofuel production. We
previously developed a two-stage transcriptional reprogramming (TSTR) strategy
(including a glucose fermentation stage and a xylose fermentation stage) and
demonstrated its application for the construction of Saccharomyces cerevisiae
strains with efficient xylose utilization. In this study, we used these as
initial strains to assess the effects of copy number variation (CNV) on optimal
gene expression and rewiring the redox balance of the xylose utilization pathway.
We obtained strains that contained several integrated copies of XYL1, XYL2, and
XKS1 and showed increased ethanol yields. An examination of the individual and
combined effects of CNVs of key genes and the redox balance pathway revealed that
the TSTR strategy improves ethanol production efficiency. Furthermore, XYL1 or
XYL2 overexpression was related to improved xylose utilization. These results
showed that strains with faster growth and/or higher ethanol production produced
more ethanol from xylose via the synthetic xylose-assimilation pathway.
Accordingly, TSTR is an effective strategy to improve xylose metabolism in
industrial yeast strains.
PMID- 29946931
TI - Exploitation of acid-tolerant microbial species for the utilization of low-cost
whey in the production of acetic acid and propylene glycol.
AB - Whey from cheese and yoghurt production operations contains useful constituents
such as whey protein and lactose. However, the separation and extraction
processes are difficult and costly, and hence, whey has limited end user demand
and is typically disposed of as waste. Treatment and disposal of these high BOD
wastes are both energy intensive and expensive. However, improper disposal of
these wastes can pollute surface and ground water resources. The use of these low
or negative cost substrates for the production of value-added products such as
acetic acid and propylene glycol (PG) is of great significance in changing
overhead costs to revenue streams. The present study focuses on bioproduction of
acetic acid and PG from whey lactose and whey powder containing lactose and
protein as an alternative to high cost nutritive medium. It was found that
Lactobacillus buchneri, an acid-tolerant bacterium, is able to ferment lactose at
pH ~ 4.2 to low molecular weight compounds such as acetic acid and PG each at 25
30 g L-1 concentration when using lactose as a major carbon substrate. The
typical molar ratio of acetic acid to PG was close to 1:1 at the end of
fermentation. The productivity of acetic acid and PG was improved using a high
cell density fermentation with cotton cheesecloth as an immobilization matrix.
The use of whey powder with immobilized fermentation system showed a similar
performance to that of cultures fed with pure lactose at pH 4.2, resulting in a
57% conversion of lactose in whey to acetate and PG in total, against a
stoichiometric maximum of 72%.
PMID- 29946932
TI - Successive transitory distribution of Thaumarchaeota and partitioned distribution
of Bathyarchaeota from the Pearl River estuary to the northern South China Sea.
AB - Thaumarchaeota and Bathyarchaeota (formerly named Miscellaneous Crenarchaeotal
Group, MCG) are globally occurring archaea playing potential roles in nitrogen
and carbon cycling, especially in marine benthic biogeochemical cycle.
Information on their distributional and compositional patterns could provide
critical clues to further delineate their physiological and biochemical
characteristics. Profiles of thaumarchaeotal and the total archaeal community in
the northern South China Sea surface sediments revealed a successively
transitional pattern of Thaumarchaeota composition using MiSeq sequencing.
Shallow-sea sediment enriched phylotypes decreased gradually along the slope from
estuarine and coastal marine region to the deep-sea, while deep-sea sediment
enriched phylotypes showed a trend of increasing. Proportion of Thaumarchaeota
within the total archaea increased with seawater depth. Phylotypes enriched in
shallow- and deep-sea sediments were affiliated to OTUs originated from similar
niches, suggesting that physiological adaption not geographical distance shaped
the distribution of Thaumarchaeota lineages. Quantitative PCR also depicted a
successive decrease of thaumarchaeotal 16S rRNA gene abundance from the highest
at shallow-sea sites E708S and E709S (2.57 * 106 and 2.73 * 106 gene copies/g of
dry sediment) to the lowest at deep-sea sites E525S and E407S (1.97 * 106 and
2.14 * 106 gene copies/g of dry sediment). Both of the abundance fractions of
Bathyarchaeota subgroups (including subgroups 1, 6, 8, 10, 13, 15, 17, and
ungrouped Bathyarchaeota) and the total Bathyarchaeota in the total archaea
showed a negative distribution to seawater depth. Partitioned distribution of
Bathyarchaeota fraction in the total archaea is documented for the first time in
this study, and the shallow- and deep-sea Bathyarchaeota could account for 17.8
and 0.8%, respectively, on average. Subgroups 6 and 8, enriched subgroups in
shallow-sea sediments, largely explained this partitioned distribution pattern
according to seawater depth. Their prevalence in shallow-sea and suboxic
estuarine sediments rather than deep-sea sediments hints that their metabolic
properties of carbon metabolism are adapted to carbon substrates in these
environments.
PMID- 29946934
TI - [Prophylactic vaccination against HP viruses for the prevention of cervical
cancer : Implementation of gender neutral, prophylactic vaccination in Germany as
an effective instrument for prevention].
PMID- 29946933
TI - An Update on Genetic Modification of Chickpea for Increased Yield and Stress
Tolerance.
AB - Chickpea is a highly nutritious grain legume crop, widely appreciated as a health
food, especially in the Indian subcontinent. The major constraints on chickpea
production are biotic (Helicoverpa, bruchid, aphid, ascochyta) and abiotic
(drought, heat, salt, cold) stresses, which reduce the yield by up to 90%.
Various strategies like conventional breeding, molecular breeding, and modern
plant breeding have been used to overcome these problems. Conventionally,
breeding programs aim at development of varieties that combine maximum number of
traits through inter-specific hybridization, wide hybridization, and
hybridization involving more than two parents. Breeding is difficult in this crop
because of its self-pollinating nature and limited genetic variation. Recent
advances in in vitro culture and gene technologies offer unique opportunities to
realize the full potential of chickpea production. However, as of date, no
transgenic chickpea variety has been approved for cultivation in the world. In
this review, we provide an update on the development of genetically modified
chickpea plants, including those resistant to Helicoverpa armigera,
Callosobruchus maculatus, Aphis craccivora, as well as to drought and salt
stress. The genes utilized for development of resistance against pod borer,
bruchid, aphid, drought, and salt tolerance, namely, Bt, alpha amylase inhibitor,
ASAL, P5CSF129A, and P5CS, respectively, are discussed.
PMID- 29946935
TI - ["Medical expulsive therapy" for ureteral stones].
PMID- 29946936
TI - ["We're going to place a ureteral stent ..." : Development and use of the terms
stent and splint by German-speaking urologists].
AB - The use of eponyms has a long history in medicine. But it is a rare case that a
term not associated with a procedure or an anatomical description has come into
use. The terms "stent" and "splint" in German and English used as a verb and a
noun are a typical example. The coronary stent was named after Charles Thomas
Stent (1807-1885). Charles Theodore Dotter (1920-1985) was the one who introduced
the eponym into the literature of angiography in 1983. The change in urology
occurred after an article of Willard Goodwin especially in the English literature
but did not come into constant use in the German language.
PMID- 29946937
TI - Long-term Management of the Arterial Switch Patient.
AB - PURPOSE OF REVIEW: This review paper describes the management of patients with
dextro-transposition of the great arteries (D-TGA) with a focus on the
complications seen and the appropriate care required to identify and prevent
adverse events. RECENT FINDINGS: D-TGA is a form of cyanotic congenital heart
disease (CHD) representing ~ 3% of all CHD and almost 20% of all cyanotic CHD.
Since the late 1980s, standard of care is to repair these patients with an
arterial switch operation (ASO) as opposed to a Mustard/Senning operation. The
long-term survival and complication rates are superior in the ASO. Long-term
follow-up is recommended for all D-TGA patients and includes management with
adult congenital heart disease specialists and the use of echocardiography and
advanced imaging with CT or MRI. The most common complications seen are pulmonary
stenosis, coronary artery stenosis, and neo-aortic regurgitation. Careful
evaluation of new symptoms or declining function is essential in preventing and
treating these long-term sequelae.
PMID- 29946939
TI - Comments to "Usefulness of Hydrogel-Coated Coils in Embolization of Pulmonary
Arteriovenous Malformations".
PMID- 29946938
TI - Multi- versus single-level anterior cervical discectomy and fusion: comparing
sagittal alignment, early adjacent segment degeneration, and clinical outcomes.
AB - PURPOSE: The purpose of this study was to compare the rates of adjacent segment
degeneration (ASD), sagittal alignment parameters, and patient-reported outcomes
in patients who underwent multi-level versus single-level anterior cervical
discectomy and fusion (ACDF). METHODS: A retrospective cohort analysis was
performed on consecutive patients who underwent an ACDF. Pre- and post-operative
radiographic assessment included ASD, change in C2-C7 lordosis, T1 angle, levels
fused, sagittal vertical axis (SVA), fusion mass lordosis, proximal and distal
adjacent segment lordosis. Patient-reported outcomes were obtained. RESULTS: Of
the 404 that underwent an ACDF with a minimum of 6 months of follow-up (average
28 months), there was no significant difference in the rate of radiographic ASD
overall (p = 0.479) or in the proximal or distal adjacent segments on
multivariate analysis. Secondarily, the multi-level fusions appear to restore
significantly greater amounts of lordosis compared to single-level procedures (p
< 0.001) and are able to maintain the corrected cervical lordosis and fusion
segment lordosis over time. From the immediate post-operative period to final
follow-up, the single-level ACDFs show continuing lordosis improvement (p =
0.005) that is significantly greater than that of the multi-level constructs.
There were no significant differences between pre-operative, post-operative, or
change in patient-reported outcomes. CONCLUSIONS: Two years following an ACDF,
patients who underwent multi-level fusions appear to restore significantly
greater amounts of lordosis compared to single-level procedures, while single
level ACDFs show significantly greater amounts of lordosis improvement over time.
Multi-level procedures may not be at a significantly greater risk of developing
early radiographic evidence of ASD compared to single-level procedure. These
slides can be retrieved under Electronic Supplementary Material.
PMID- 29946940
TI - Stent Fracture After Transjugular Intrahepatic Portosystemic Shunt: Reply.
PMID- 29946941
TI - Comparison of Radiofrequency Ablation and Transarterial Chemoembolization for
Hepatocellular Carcinoma in the Caudate Lobe.
AB - BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) in the caudate lobe is
technically challenging for both radiofrequency ablation (RFA) and transarterial
chemoembolization (TACE). However, each of these modalities has its strengths.
This retrospective study compares the effectiveness of RFA and TACE in patients
with caudate HCC within the Milan criteria. METHODS: This study was approved by
institutional review board. Between November 2005 and August 2016, we
retrospectively reviewed 74 patients with a single HCC <= 5 cm or up to three
HCCs <= 3 cm without vascular invasion or extrahepatic metastasis who were
treated with RFA (n = 43) or TACE (n = 31). The overall survival (OS) and local
progression rates were compared after propensity score analysis. RESULTS: The
mean follow-up period was 2.8 +/- 1.9 years. The 1-, 2-, and 3-year survival
rates were 97.1, 94.0, and 80.7% for the RFA group and 89.0, 80.8, and 62.0% for
the TACE group, respectively. The clinical variables of the RFA and the TACE
groups were well balanced by propensity score adjustment, and the RFA group
showed better OS (P = .039) and local progression rates (P = .004) than the TACE
group. CONCLUSIONS: RFA appears to outperform TACE for patients with caudate HCC
within the Milan criteria and should be the favored treatment option when
surgical resection is not feasible.
PMID- 29946943
TI - Primary Tumor Location in Colorectal Cancer: Comparison of Right- and Left-Sided
Colorectal Cancer Characteristics for the Interventional Radiologist.
AB - One area which has emerged as an important factor for predicting molecular
profile and treatment outcomes in metastatic colorectal cancer (mCRC) is primary
tumor location. The importance of molecular characteristics of colorectal cancer
has been firmly established in terms of prognosis and treatment algorithms for
many years. Recent studies have also suggested that molecular profiles are
important in locoregional therapies as well, with some data suggesting changes in
treatment algorithms based on tumor location. Therefore, it is important for
interventional radiologists to understand the basic molecular characteristics and
development pathways of mCRC. Here, these disease characteristics are reviewed
and the differences in left- versus right-sided primary tumor location are
explored.
PMID- 29946942
TI - Percutaneous Antegrade Colonic Stent Insertion Using a Proximal Trans-peritoneal
Colopexy Technique.
AB - INTRODUCTION: Conventionally, colonic stents are inserted with a retrograde trans
anal approach-however, stenting of right-sided or proximal transverse colon
lesions may pose a challenge due to tortuosity or long distances. We report three
successful cases of percutaneous antegrade colonic stenting in patients using a
proximal trans-peritoneal colopexy technique. MATERIALS AND METHODS: Three
patients underwent a proximal trans-peritoneal colopexy technique for antegrade
colonic stent placement. The patients included three males, ages 89, 92 and 55,
who were unsuitable for conventional methods. All patients had a colopexy with
the aid of three gastropexy sutures performed under CT or fluoroscopic guidance
and subsequent colonic access, followed by the crossing lesion and subsequent
deployment of an uncovered colonic stent. A 10-Fr pigtail catheter was exchanged
for the sheath, capped and left in place along with the colopexy suture anchors.
RESULTS: Percutaneous antegrade colonic stent placement was technically
successful in all patients with no complications. Follow-up at 10 days, a
tubogram confirmed stent patency. The pigtail drain and suture anchors were
subsequently removed. CONCLUSION: Antegrade colonic stenting with the use of a
three point colopexy is a straightforward well-tolerated procedure and is a
useful technique in a cohort of patients in whom conventional stenting has
failed/is unsuitable. Additionally, we believe we have reported the first two
cases involving transverse colon access for stenting.
PMID- 29946944
TI - Just How Attractive is the ATTRACT Trial?
AB - Venous thromboembolism (VTE) is a major public health issue; deep vein thrombosis
(DVT) affects about 1/1000 patients. Each year, VTE kills more patients in
Western Europe than breast cancer, prostate cancer, acquired immune deficiency
syndrome (AIDS) and road traffic accidents combined and is responsible for the
deaths of approximately 370,000 European citizens (Cohen et al. in Thromb Haemost
98:756-764, 2007; Belohlavek et al. in Exp Clin Cardiol 18(2):129-138, 2013). The
recently published ATTRACT trial (Acute Venous Thrombosis Thrombus Removal with
Adjunctive Catheter-directed Thrombolysis) (Vedantham et al. in N Engl J Med
377:2240-2252, 2017) concluded that the addition of catheter-directed
thrombolysis to standard therapy with anticoagulation and compression stockings
offers no significant clinical benefit over standard therapy in terms of
reduction in the rate of post-thrombotic syndrome (PTS) at 2 years. It is the
largest, prospective, multi-centre, randomised controlled trial (RCT) and
represents the culmination over a decade of planning, execution and analysis. In
this opinion article, we analyse why it was needed, what it demonstrated, some
limitations, and the directions in which this important publication will take us.
PMID- 29946945
TI - A French update on the Self-Efficacy Measure for Sleep Apnea (SEMSA) to assess
continuous positive airway pressure (CPAP) use.
AB - PURPOSE: The Self-Efficacy Measure for Sleep Apnea (SEMSA) is a 26-item self
questionnaire composed of three factors: risk perception of obstructive sleep
apnea syndrome (OSAS), benefit of continuous positive airway pressure (CPAP), and
self-efficacy (the confidence to engage in CPAP use). It is used to evaluate
health beliefs about OSAS and CPAP in order to optimize CPAP use. The purpose of
this study was to design and validate a French version of the SEMSA. METHODS: A
forward-backward translation of the SEMSA was performed. Subjects with OSAS
treated by CPAP and followed by our sleep clinic were invited to complete the
questionnaire. The psychometric properties of the French SEMSA version were
analyzed in terms of its construct validity (with confirmatory factor analysis,
CFA), internal structural validity (Cronbach's alpha coefficient), and external
validity (Pearson's correlation between SEMSA score and duration of CPAP use).
RESULTS: Two hundred eighty-eight subjects filled in the questionnaire. The mean
age was 63.16 +/- 12.73 years. The number of years since the beginning of CPAP
treatment was 6.58 +/- 6.03 years. The mean CPAP use duration was 6.19 +/- 2.03
h/night. CFA was unsatisfactory (RMSEA = 0.066 and CFI = 0.88). The exploratory
factor analysis revealed a fourth factor named "cardiovascular risk" factor.
Cronbach's alpha coefficient was 0.886. The correlation between the "self
efficacy" factor and the duration of CPAP use was significant (r = 0.26, p <=
0.001). CONCLUSIONS: The French version of the SEMSA is a psychometrically
acceptable self-report questionnaire for measuring health beliefs and behavior in
French patients with OSAS treated with CPAP. Such translation and validation
should lead to the adoption of validated psychosocial methods for improving CPAP
use.
PMID- 29946946
TI - Arterial stiffness alteration and obstructive sleep apnea in an elderly cohort
free of cardiovascular event history: the PROOF cohort study.
AB - INTRODUCTION: Several studies suggest in middle-aged subjects a relationship
between arterial stiffness, a cardiovascular risk marker, and moderate to severe
obstructive sleep apnea (OSA). No extensive data are present in older subjects.
This study explores this association in a sample of healthy older subjects
suffering OSA. METHODS: A total of 101 volunteers aged 75.3 +/- 0.7 years were
examined at the hospital sleep center. Each subject was assessed for medical
history, body mass index and 24-h blood pressure measures, biological blood
samples, and home polygraphy in 2002-2003 (P2) as well as in 2009-2010 (P4).
Arterial stiffness was also assessed using carotid-femoral and carotid-radial
pulse wave velocity (cfPWV and crPWV) during P4 examination. RESULTS: The total
group consisted of 59 women and 42 men with a mean apnea-hypopnea index (AHI) of
17.8 +/- 12.1 and a mean oxygen desaturation index (ODI) of 9.8 +/- 8.9. No-OSA
(AHI < 15) represented 50% of the sample, and severe cases (AHI > 30) 17%. No
significant differences had been founded between men and women for blood
pressure, cfPWV, and crPWV. Considering the severity of the AHI, no significant
differences between groups were present for PWV and blood pressure values. No
difference for PWV was present for subjects with and without hypertension. No
correlation was found between PWV value and AHI and ODI values at P2 or between
P2 and P4 visits. cfPWV was higher in patients demonstrating incident
hypertension during the follow-up. CONCLUSIONS: In this sample of older subjects,
PWV is not affected by AHI and ODI but was associated with incident hypertension.
These results may suggest potential protective and adaptive mechanisms in older
sleep apnea patients. CLINICAL TRIAL REGISTRATIONS: NCT 00759304 and NCT 00766584
.
PMID- 29946947
TI - Serum levels of NGAL and cystatin C as markers of early kidney dysfunction in
patients with obstructive sleep apnea syndrome.
AB - PURPOSE: Obstructive sleep apnea syndrome (OSAS) has been recently proposed as an
independent risk factor for chronic kidney disease. Cystatin C (Cyst C) and
neutrophil gelatinase-associated lipocalin (NGAL) are novel biomarkers for the
earlier detection of latent kidney disease. The aim of the study was to assess
serum Cyst C and NGAL levels in otherwise healthy OSAS patients and to explore
possible associations with sleep parameters. METHODS: Consecutive subjects (n =
96, 79.2% males), without known comorbidities, with symptoms suggestive of OSAS
were included. All of them underwent polysomnography (PSG) and blood examination
for the measurement of serum Cyst C and NGAL levels. RESULTS: Based on apnea
hypopnea index (AHI), subjects were classified into two groups: 32 controls and
64 OSAS patients, with no significant differences in terms of age (50.1 +/- 11.7
vs 51 +/- 12.2 years, p = 0.747) and BMI (33.9 +/- 8.8 vs 35.9 +/- 13.1 kg/m2, p
= 0.449). Serum Cyst C and NGAL mean levels were higher in OSAS patients compared
to those in controls (1155.2 +/- 319.3 vs 966.8 +/- 173 ng/ml, p = 0.001, and
43.7 +/- 23.2 vs 35.6 +/- 13.8 ng/ml, p = 0.035, respectively). After adjustment
for age and BMI in OSAS patients, serum NGAL levels were associated with AHI
(beta = 0.341, p = 0.015) and minimum oxyhemoglobin saturation during sleep (beta
= - 0.275, p = 0.032), while serum Cyst C levels were associated with percentage
of time with oxyhemoglobin saturation < 90% (beta = 0.270, p = 0.043), average
(beta = - 0.308, p = 0.018), and minimum (beta = - 0.410, p = 0.001)
oxyhemoglobin saturation during sleep. CONCLUSIONS: Higher risk for latent kidney
disease in otherwise healthy OSAS patients is indicated. Sleep hypoxia seems to
be a significant contributor in the pathogenetic process of renal dysfunction in
OSAS.
PMID- 29946948
TI - Depigmenting effect of argan press-cake extract through the down-regulation of
Mitf and melanogenic enzymes expression in B16 murine melanoma cells.
AB - Oil extraction from the kernels of Argania spinosa (L.) Skeels (Sapotaceae), an
endemic tree of Morocco, produces argan press-cake (APC) used as a shampoo and to
treat sprains, scabies, and for healing wounds. We have previously reported that
argan oil has antimelanogenesis effect. Here, we determined if the by-product,
APC, has melanogenesis regulatory effect using B16 murine melanoma cells. The
effect of APC ethanol extract on cell proliferation and melanin content of B16
cells were measured, and to elucidate the mechanism involved, the expression
level of melanogenic enzymes tyrosinase (TYR), dopachrome tautomerase (DCT), and
tyrosinase-related protein 1 (TRP1) were determined and mRNA expression level of
microphthalmia- associated transcription factor (Mitf) and Tyr genes were
quantified. APC ethanol extract showed a significant melanin biosynthesis
inhibitory effect on B16 cells in a time-dependent manner without cytotoxicity,
which could be due to the decreased expression of TYR, TRP1, and DCT in a time
dependent manner. APC extract down regulated Mitf and Tyr. Decreased TRP1 and DCT
levels could be due to post-translational modifications. These results suggest
that APC extract may be used as a new source of natural whitening products and
may be introduced as an important pharmacological agent for the treatment of
hyperpigmentation disorders.
PMID- 29946949
TI - Bioactivity evaluation of collagen-based scaffolds containing a series of Sr
doped melt-quench derived phosphate-based glasses.
AB - Phosphate-based glasses have been attracting attention due to their possible
medical applications arising from unique dissolution characteristics in the human
body leading to the possibility of new tissue regeneration. In this study, the
leaching kinetics of a series of melt-quenched Sr-doped phosphate glasses are
presented. Regardless of the presence of Sr, all the glasses have an initial
linear and sustained release of the ions followed by a plateau. To guarantee
proper nutritional support to the growing tissue during regeneration and to mimic
the 3-dimensional architecture of tissues, organic scaffold systems have been
developed. However, their poor mechanical strength has limited their application.
To overcome this problem, cross-linkers can be used although this then limits the
solubility of the materials. To succeed in dealing with such a limitation, in
this paper, by freeze-drying, the aforementioned soluble melt-quenched phosphate
glasses were combined as powders with collagen fibres from bovine achilles tendon
to make degradable scaffolds. The scaffolds were characterized by SEM, EDX and
BET. Changes to the dissolution behaviour of the glasses arising from the
presence of collagen interacting with the ions leached were reported.
Furthermore, the ability of the scaffolds to induce hydroxyapatite (HA) formation
was evaluated: one the elaborated scaffold could grow an HA-like layer after a
week in SBF. Based on the results obtained, a possible application in restorative
dentistry is proposed for one or more materials.
PMID- 29946951
TI - Are mind wandering rates an artifact of the probe-caught method? Using self
caught mind wandering in the classroom to test, and reject, this possibility.
AB - Mind wandering (MW) reports often rely on individuals responding to specific
external thought probes. Researchers have used this probe-caught method almost
exclusively, due to its reliability across a wide range of testing situations.
However, it remains an open question whether the probe-caught MW rates in more
complex settings converge with those for simpler tasks, because of the rather
artificial and controlled nature of the probe-caught methodology itself, which is
shared across the different settings. To address this issue, we measured MW in a
real-world lecture, during which students indicated whether they were mind
wandering by simply catching themselves (as one would normally do in real life)
or by catching themselves and responding to thought probes. Across three separate
lectures, self-caught MW reports were stable and unaffected by the inclusion of
MW probes. That the probe rates were similar to those found in prior classroom
research and did not affect the self-caught MW rates strongly suggests that the
past consistency of probe-caught MW rates across a range of different settings is
not an artifact of the thought-probe method. Our study also indicates that the
self-caught MW methodology is a reliable way to acquire MW data. The extension of
measurement techniques to include students' self-caught reports provides valuable
information about how to successfully and naturalistically monitor MW in lecture
settings, outside the laboratory.
PMID- 29946950
TI - Distinct [18F]THK5351 binding patterns in primary progressive aphasia variants.
AB - PURPOSE: To assess the binding of the PET tracer [18F]THK5351 in patients with
different primary progressive aphasia (PPA) variants and its correlation with
clinical deficits. The majority of patients with nonfluent variant (NFV) and
logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar
or Alzheimer disease type, respectively, while patients with the semantic variant
(SV) have predominantly transactive response DNA binding protein 43-kDa
pathology. METHODS: The study included 20 PPA patients consecutively recruited
through a memory clinic (12 NFV, 5 SV, 3 LV), and 20 healthy controls. All
participants received an extensive neurolinguistic assessment, magnetic resonance
imaging and amyloid biomarker tests. [18F]THK5351 binding patterns were assessed
on standardized uptake value ratio (SUVR) images with the cerebellar grey matter
as the reference using statistical parametric mapping. Whole-brain voxel-wise
regression analysis was performed to evaluate the association between
[18F]THK5351 SUVR images and neurolinguistic scores. Analyses were performed with
and without partial volume correction. RESULTS: Patients with NFV showed
increased binding in the supplementary motor area, left premotor cortex,
thalamus, basal ganglia and midbrain compared with controls and patients with SV.
Patients with SV had increased binding in the temporal lobes bilaterally and in
the right ventromedial frontal cortex compared with controls and patients with
NFV. The whole-brain voxel-wise regression analysis revealed a correlation
between agrammatism and motor speech impairment, and [18F]THK5351 binding in the
left supplementary motor area and left postcentral gyrus. Analysis of
[18F]THK5351 scans without partial volume correction revealed similar results.
CONCLUSION: [18F]THK5351 imaging shows a topography closely matching the
anatomical distribution of predicted underlying pathology characteristic of NFV
and SV PPA. [18F]THK5351 binding correlates with the severity of clinical
impairment.
PMID- 29946952
TI - Modeling the dependence of the distortion product otoacoustic emission response
on primary frequency ratio.
AB - When measured as a function of primary frequency ratio r = f2/f1, using a
constant f2, distortion product otoacoustic emission (DPOAE) response
demonstrates a bandpass shape, previously interpreted as the evidence for a
cochlear "second filter." In this study, an alternate, interference-based
explanation, previously advanced in variants, is forwarded on the basis of
experimental data along with numerical and analytical solutions of nonlinear and
linear cochlear models. The decrease of the DPOAE response with increasing and
decreasing ratios is explained by a diminishing "overlap" generation region and
the onset of negative interference among wavelets of different phase,
respectively. In this paper, the additional quantitative hypothesis is made that
negative interference becomes the dominant effect when the spatial width of the
generation (overlap) region exceeds half a wavelength of the DPOAE wavelets.
Therefore, r is predicted to be optimal when this condition is matched.
Additionally, the minimum on the low-ratio side of the DPOAE curve is predicted
to occur as the overlap region width equals one wavelength. As the width of the
overlap region depends on both tuning and ratio, while wavelength depends on
tuning only, an experimental method for estimating tuning from either the width
of the pass band or the optimal ratio of the DPOAE vs. ratio curve has been
theoretically formulated and evaluated using numerical simulations. A linear
model without the possibility of nonlinear suppression is shown to reasonably
approximate data from human subjects at low ratios reinforcing the relevance of
the proposed negative interference effect. The different dependence of the
distortion and reflection DPOAE components on r as well as the nonmonotonic
behavior of the distortion component observed at very low ratios are also in
agreement with this interpretation.
PMID- 29946953
TI - The Cost of Complications Following Major Resection of Malignant Neoplasia.
AB - BACKGROUND: Rising healthcare costs have led to increased focus on the need to
achieve a higher "value of care." As value-maximization efforts expand to include
more complex surgical patients, evidence to support meaningful implementation of
complication-based initiatives is lacking. The objective of this study was to
compare incremental costs of complications following major gastrointestinal (GI)
resections for organ-specific malignant neoplasia using nationally representative
data. METHODS: National (Nationwide) Inpatient Sample data, 2001-2014, were
queried for adult (>= 18 years) patients undergoing major resections for
malignant neoplasia. Based on system-based complications considered relevant to
the long-term treatment of GI disease, stratified differences in risk-adjusted
incremental hospital costs and complication probabilities were compared.
Differences in surgical outcomes and costs over time were also assessed. RESULTS:
A total of 293,967 patients were included, weighted to represent 1,408,117
patients nationwide. One fourth (26.1%; 95% CI, 25.7-26.4%) experienced >= 1 pre
discharge complication (range, 45.3% esophagectomy to 24.0% rectal resection).
Resultant annual risk-adjusted incremental hospital costs totaled $540 million
nationwide (19.5% of the overall cost of care and an average of $20,900 per
patient). Costs varied substantially with both cancer/resection type and
complication group, ranging from $76.7 million for colectomies with infectious
complications to $0.2 million for rectal resections with urinary complications.
For each resection type, infectious ($154.7 million), GI ($85.5 million), and
pulmonary ($77.9 million) complications were among the most significant drivers
of increased hospital cost. CONCLUSIONS: Quantifying and comparing the impact of
complications on an indication-specific level in more complex patients offers an
important step toward allowing providers/payers to meaningfully prioritize the
design of novel and adaptation of existing value-maximization approaches.
PMID- 29946954
TI - Ultrasound-assisted extraction based on QuEChERS of pesticide residues in
honeybees and determination by LC-MS/MS and GC-MS/MS.
AB - In this work, 260 pesticide residues, including insecticides, acaricides,
fungicides, and herbicides, were extracted from honeybees using the QuEChERS
methodology modified by applying an ultrasonic probe, which avoided the
homogenization step and reduced the extraction time. Gas and liquid
chromatography, both coupled to triple-quadrupole mass spectrometry, allowed the
determination of the pesticide residues extracted from the samples. The
optimization of the main ultrasonic conditions (sonication amplitude, number of
cycles, and time of each cycle) was performed using a Box-Behnken experimental
design involving 15 experimental samples. The results obtained with this approach
showed that the recoveries were not affected by these experimental parameters for
95 pesticide residues whereas the sonication amplitude was the main factor
affecting the recoveries of 107 pesticide residues. The extraction time and the
number of cycles affected four and one pesticide residues, respectively. The
effectiveness of the ultrasonic-assisted extraction without homogenization of the
honeybee samples compared favorably with that for the conventional QuEChERS
methodology applied to the same previously homogenized samples. The proposed
methodology was validated according to the SANTE/11945/2015 guidelines, with a 5
MUg/kg limit of quantitation. Recoveries between 70 and 120% and relative
standard deviations lower than 20% were obtained for most analytes. Thirty
honeybee samples taken from Spanish apiaries were analyzed using this new
methodology. The results revealed the presence of 30 different pesticide residues
in the honeybee samples, the highest concentration levels corresponding to
certain insecticides/acaricides used by beekeepers to control Varroa destructor.
Permethrin, thiabendazole, carbendazim, and coumaphos were the most frequently
detected pesticide residues in the selected samples.
PMID- 29946955
TI - Gait stability in response to platform, belt, and sensory perturbations in young
and older adults.
AB - Perturbation-based gait assessment has been used to quantify gait stability in
older adults. However, knowledge on which perturbation type is most suitable to
identify poor gait stability is lacking. We evaluated the effects of ipsi- and
contra-lateral sway, belt acceleration and deceleration, and visual and auditory
perturbations on medio-lateral (ML) and anterior-posterior (AP) margins of
stability (MoS) in young and older adults. We aimed to evaluate (1) which
perturbation type disturbed the gait pattern substantially, (2) how participants
recovered, and (3) whether recovery responses could discriminate between young
and older adults. Nine young (25.1 +/- 3.4 years) and nine older (70.1 +/- 7.6
years) adults walked on the CAREN Extended (Motek BV, The Netherlands). The
perturbation effect was quantified by deviation in MoS over six post-perturbation
steps compared to baseline walking. Contra-lateral sway and deceleration
perturbations resulted in the largest ML (1.9-4 times larger than other types)
and AP (1.6-5.6 times larger than other types) perturbation effects,
respectively. After both perturbation types, participants increased MoS by taking
wider, shorter, and faster steps. No differences between young and older adults
were found. We suggest to evaluate the potential of using contra-lateral sway and
deceleration perturbations for fall risk identification by including both healthy
and frail older adults. Graphical abstract Margins of stability during steady
state (left) and perturbed (right) gait to quantify reactive gait stability in
response to various perturbation types in young and older adults.
PMID- 29946956
TI - Metabolic profile of oxidative stress and trace elements in febrile seizures
among children.
AB - Febrile seizures (FS) are frequent convulsive disorders, occurring in infants and
young children. The present study aims to assess and compare the serum levels of
oxidative stress markers and some essential trace minerals in FS with normal or
abnormal EEG and evaluate the effect of antioxidant therapy on the clinical
outcome. This study has been carried out on 80 children with FS (40 with simple
FS and 40 with complex FS) and 40 febrile children without seizures. Clinical and
EEG findings were recorded for the included patients. Biochemical assays of serum
nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), copper
(Cu), zinc (Zn) and selenium (Se), using colorimetric methods, were measured in
the studied groups. The overall results showed an increased values of NO, MDA and
Cu with decreased values of SOD, Zn and Se in patients with FS (simple and
complex) in comparison with febrile children without seizures (p < 0.05 for all).
Additionally, NO and MDA was increased in complex FS patients with EEG
abnormalities in comparison with complex FS with normal EEG findings (p < 0.05);
NO and MDA were also significantly decreased after valproate therapy in complex
FS patients (p < 0.05 for all). In conclusions, oxidative stress, decreased Zn
and Se with increased Cu may play a role in FS. Valproate improves the oxidative
stress status in complex FS.
PMID- 29946957
TI - Impact of swimming exercise on inflammation in medullary areas of sympathetic
outflow control in spontaneously hypertensive rats.
AB - Exercise reduces sympathetic activity (SA), arterial pressure and heart rate in
spontaneously hypertensive rats (SHR). Exercise increases oxidative stress (OS)
and inflammation is implicated in the generation of reactive oxygen species (ROS)
and progression of hypertension. To unravel these effects of exercise and
considering that SA is driven by medullary areas, we hypothesized that swimming
exercise (SW) affects the gene expression (g.e.) of proteins involved in
inflammation and OS in the commissural Nucleus of the Solitary Tract (cNTS) and
Rostral ventrolateral medulla (RVLM), which control the sympathetic outflow in
SHR. We used male SHR and Wistar rats (14-16wks-old) which were maintained
sedentary (SED) or submitted to SW (1 h/day, 5 days/wk./6wks). The g.e. of
cycloxygenase-2 (COX-2), interleukin 6 (IL-6), interleukin 10 (IL-10), AT-1
receptor (AT-1r), neuroglobin (Ngb) and cytoglobin (Ctb) in cNTS and RVLM was
carried out by qPCR. We observed that COX-2 g.e. increased in SW-SHR in cNTS and
RVLM compared to SED-SHR. The IL-6 g.e. reduced in RVLM in SW-SHR, whereas IL-10
g.e. increased in SW-SHR in comparison to SED-SHR. The AT-1r g.e. decreased in SW
SHR in cNTS and RVLM compared to SED-SHR. The Ngb and Ctb g.e. in cNTS neurons
increased in SHR and Wistar rats submitted to SW compared to SED, but only Ctb
g.e. increased in RVLM in SW-SHR and Wistar in comparison to SED. Therefore, the
SW altered the g.e. in cNTS and RVLM for reducing the inflammation and ROS
formation, which is increased particularly in SHR, consequently decreasing the
OS.
PMID- 29946958
TI - Effect of methamphetamine on the fasting blood glucose in methamphetamine
abusers.
AB - Methamphetamine is a popular psychostimulant worldwide which causes neurotoxicity
and neuroinflammation. Although previous studies have characterized potential
associations between addictive drugs and fasting blood glucose, the influence of
methamphetamine on the blood glucose is still largely unknown. The present study
was designed to investigate the change of fasting blood glucose of
methamphetamine abusers and to confirm the impairment of liver and kidney.
Fasting blood glucose was significantly decreased in methamphetamine abusers and
in a high-fat diet mouse model with methamphetamine treatment discontinuation.
Serum level of ALT, creatine kinase and creatinine were increased in
methamphetamine abusers. Serum level of ALT and AST were increased in a high-fat
diet mouse model after methamphetamine injection, but there was no significant
difference in the anatomy of the liver and kidney in high-fat diet treated mice
with or without methamphetamine. The levels of ALT and creatinine were also
increased in the methamphetamine abusers. This study demonstrated that the level
of glucose was decreased in methamphetamine abusers and in high-fat diet-fed mice
after methamphetamine treatment discontinuation. The effect of methamphetamine on
the levels of blood glucose may provide the evidence that methamphetamine abusers
should be keep energy balance due to the low blood glucose.
PMID- 29946959
TI - Metabolic fate of glucose in the brain of APP/PS1 transgenic mice at 10 months of
age: a 13C NMR metabolomic study.
AB - Alzheimer's disease (AD) has been associated with the disturbance of brain
glucose metabolism. The present study investigates brain glucose metabolism using
13C NMR metabolomics in combination with intravenous [1-13C]-glucose infusion in
APP/PS1 transgenic mouse model of amyloid pathology at 10 months of age. We found
that brain glucose was significantly accumulated in APP/PS1 mice relative to wild
type (WT) mice. Reductions in 13C fluxes into the specific carbon sites of
tricarboxylic acid (TCA) intermediate (succinate) as well as neurotransmitters
(glutamate, glutamine, gamma-aminobutyric acid and aspartate) from [1-13C]
glucose were also detected in the brain of APP/PS1 mice. In addition, our results
reveal that the 13C-enrichments of the C3 of alanine were significantly lower and
the C3 of lactate have a tendency to be lower in the brain of APP/PS1 mice than
WT mice. Taken together, the development of amyloid pathology could cause a
reduction in glucose utilization and further result in decreases in energy and
neurotransmitter metabolism as well as the lactate-alanine shuttle in the brain.
PMID- 29946961
TI - [Neurobiology of opioid dependence].
AB - Opioid dependence is a chronic mental disease with multifactorial etiology. The
neurobiological theory of addiction focuses on the manipulation of the
dopaminergic reward system as a basic property of substances with addictive
potential including opioids. With regular opioid intake, the manipulation of the
reward system results in a cognitive bias towards drug-related stimuli. In
addition, opioids inhibit the locus caeruleus, resulting in symptoms of
sympathetic rebound during opioid detoxification. The pharmacokinetics of opioids
also influence the risk of addiction. These biological factors are independent of
the legal status of the individual opioid. Genetics also significantly influence
the etiology. However, the assignment of this genetic influence is difficult
because not only basic biological functions, but also personality traits and
mental illnesses are genetically determined.
PMID- 29946960
TI - [Psychosocial risk factors for chronic back pain in the general population and in
competitive sports : From theory to clinical screening-a review from the MiSpEx
network].
AB - BACKGROUND: Lumbar back pain and the high risk of chronic complaints is not only
an important health concern in the general population but also in high
performance athletes. In contrast to non-athletes, there is a lack of research
into psychosocial risk factors in athletes. Moreover, the development of
psychosocial screening questionnaires that would be qualified to detect athletes
with a high risk of chronicity is in the early stages. The purpose of this review
is to give an overview of research into psychosocial risk factors in both
populations and to evaluate the performance of screening instruments in non
athletes. METHODS: The databases MEDLINE, PubMed, and PsycINFO were searched from
March to June 2016 using the keywords "psychosocial screening", "low back pain",
"sciatica" and "prognosis", "athletes". We included prospective studies conducted
in patients with low back pain with and without radiation to the legs, aged >=18
years and a follow-up of at least 3 months. RESULTS: We identified 16 eligible
studies, all of them conducted in samples of non-athletes. Among the most
frequently published screening questionnaires, the Orebro Musculoskeletal Pain
Screening Questionnaire (OMPSQ) demonstrated a sufficient early prediction of
return to work and the STarT Back Screening Tool (SBT) revealed acceptable
performance predicting pain-related impairment. The prediction of future pain was
sufficient with the Risk Analysis of Back Pain Chronification (RISC-BP) and the
Heidelberg Short Questionnaire (HKF). CONCLUSION: Psychosocial risk factors of
chronic back pain, such as chronic stress, depressive mood, and maladaptive pain
processing are becoming increasingly more recognized in competitive sports.
Screening instruments that have been shown to be predictive in the general
population are currently being tested for suitability in the German MiSpEx
research consortium.
PMID- 29946964
TI - What is the cause of P-wave undersensing in this CRT-D device?
PMID- 29946962
TI - Current and Emerging Therapeutics for the Management of Endometriosis.
AB - Endometriosis is a chronic benign disease that affects women of reproductive age.
Medical therapy is often the first line of management for women with
endometriosis in order to ameliorate symptoms or to prevent post-surgical disease
recurrence. Currently, there are several medical options for the management of
patients with endometriosis. Non-steroidal anti-inflammatory drugs (NSAIDs) are
widely used in the treatment of chronic inflammatory conditions, being
efficacious in relieving primary dysmenorrhea. Combined oral contraceptives
(COCs) and progestins, available for multiple routes of administration, are
effective first-line hormonal options. In fact, several randomized controlled
trials (RCTs) demonstrated that they succeed in improving pain symptoms in the
majority of patients, are well tolerated and not expensive. Second-line therapy
is represented by gonadotropin-releasing hormone (GnRH) agonists. Even if these
drugs are efficacious in treating women not responding to COCs or progestins,
they are not orally available and have a less favorable tolerability profile
(needing an appropriate add-back therapy). The use of danazol is limited by the
large availability of other better-tolerated hormonal drugs. Because few data are
available on long-term efficacy and safety of aromatase inhibitors they should be
administered only in women with symptoms refractory to other conventional
therapies in a clinical research setting. Promising preliminary data have emerged
from multicenter Phase III trials on elagolix, a new oral GnRH antagonist but non
inferiority RCT data are required to compare elagolix with first-line therapies
for endometriosis.
PMID- 29946963
TI - Empagliflozin: A Review in Type 2 Diabetes.
AB - Empagliflozin (Jardiance(r)), a potent, highly selective, sodium glucose
cotransporter-2 (SGLT2) inhibitor, is an effective and generally well tolerated
antihyperglycaemic agent approved for the treatment of adults with type 2
diabetes (T2D) in the EU, USA and Japan, among other parts of the world. As with
other members of its class, empagliflozin offers the convenience of once-daily
oral administration and carries a low inherent risk of hypoglycaemia as a result
of its insulin-independent mechanism of action, enabling it to be used as
monotherapy and as a component of combination therapy with other antidiabetic
agents with complementary modes of action to improve glycaemic control in
patients with T2D. Beyond lowering glucose, empagliflozin exerts a favourable
effect on a number of nonglycaemic outcomes, including modest reductions in
bodyweight and blood pressure. As an adjunct to standard care, it demonstrated
cardioprotective and renoprotective properties largely independent of glycaemic
control in patients with T2D and established cardiovascular disease (CVD) in a
mandated cardiovascular (CV) outcomes trial (EMPA-REG OUTCOME). Empagliflozin is
generally well tolerated as monotherapy or as add-on therapy and, unlike
canagliflozin (the only other SGLT2 inhibitor that has so far shown CV and renal
benefits), it has not been associated with an increased risk of amputation or
bone fractures. In conclusion, empagliflozin is a valuable treatment option for
the management of T2D. Given its demonstrable cardioprotective benefits, the drug
is worthy of preferential consideration in patients at high CV risk who require
an (additional) antidiabetic medication in order to attain their glycaemic goal.
PMID- 29946965
TI - Rather rule than exception? How to evaluate the relevance of dual protein
targeting to mitochondria and chloroplasts.
AB - Dual targeting of a nuclearly encoded protein into two different cell organelles
is an exceptional event in eukaryotic cells. Yet, the frequency of such dual
targeting is remarkably high in case of mitochondria and chloroplasts, the two
endosymbiotic organelles of plant cells. In most instances, it is mediated by
"ambiguous" transit peptides, which recognize both organelles as the target. A
number of different approaches including in silico, in organello as well as both
transient and stable in vivo assays are established to determine the targeting
specificity of such transit peptides. In this review, we will describe and
compare these approaches and discuss the potential role of this unusual targeting
process. Furthermore, we will present a hypothetical scenario how dual targeting
might have arisen during evolution.
PMID- 29946967
TI - Methodological issues related to maximal fat oxidation rate during exercise :
Comment on: Change in maximal fat oxidation in response to different regimes of
periodized high-intensity interval training (HIIT).
PMID- 29946966
TI - Identification of potential organ donors after aneurysmal subarachnoid hemorrhage
in a population-based neurointensive care in Eastern Finland.
AB - BACKGROUND: To analyze the organ donation action in population-based
neurointensive care of acute aneurysmal subarachnoid hemorrhage (aSAH) and to
seek factors that would improve the identification of potential organ donors
(PODs) and increase the donor conversion rate (DCR) after aSAH. METHODS: The
Kuopio Intracranial Aneurysm Database, prospective since 1995, includes all aSAH
patients admitted to the Kuopio University Hospital (KUH) from its defined
Eastern Finnish catchment population. We analyzed 769 consecutive acute aSAH
patients from 2005 to 2015, including their data from the Finnish Transplantation
Unit and the national clinical registries. We analyzed PODs vs. actual donors
among the 145 (19%) aSAH patients who died within 14 days of admission. Finland
had implemented the national presumed consent (opt-out) within the study period
in the end of 2010. RESULTS: We retrospectively identified 83 (57%) PODs while
only 49 (34%) had become actual donors (total DCR 59%); the causes for non
donorship were 15/34 (44%) refusals of consent, 18/34 (53%) medical
contraindications for donation, and 1/34 (3%) failure of recognition. In 2005
2010, there were 11 refusals by near relatives with DCR 52% (29/56) and only
three in 2011-2015 with DCR 74% (20/27). Severe condition on admission (Hunt and
Hess grade IV or V) independently associated with the eventual POD status.
CONCLUSIONS: Nearly 20% of all aSAH patients acutely admitted to neurointensive
care from a defined catchment population died within 14 days, almost half from
cardiopulmonary causes at a median age of 69 years. Of all aSAH patients, 11%
were considered as potential organ donors (PODs). Donor conversion rate (DCR) was
increased from 52 to 74% after the national presumed consent (opt-out).
Implicitly, DCR among aSAH patients could be increased by admitting them to the
intensive care regardless of dismal prognosis for the survival, along a dedicated
organ donation program for the catchment population.
PMID- 29946968
TI - Assessment of the two-point method applied in field conditions for routine
testing of muscle mechanical capacities in a leg cycle ergometer.
AB - PURPOSE: The aim of this study was to compare the reliability and magnitude of
the force-velocity (F-V) relationship parameters [maximum force (F0), maximum
velocity (V0), F-V slope, and maximum power (P0)] obtained through the
application of only two loads (i.e., two-point method) vs. six loads (i.e.,
multiple-point method). METHODS: Ten physically active men (age 19.5 +/- 0.9
years, body mass 79.0 +/- 9.0 kg, height 183.9 +/- 8.4 cm) conducted four testing
sessions after a preliminary familiarization session with the leg cycle ergometer
exercise. In a counterbalanced order, subjects performed two sessions of the
multiple-point method (six loads applied for the F-V modeling) over 1 week and
two sessions of the two-point method (only the lightest and heaviest loads were
applied) over another week. RESULTS: The main findings revealed that (I) the
reliability of the F-V relationship parameters was very high and generally of
comparable magnitude for both the multiple- [coefficient of variation (CV) range
1.91-3.94%; intraclass correlation coefficient (ICC) range 0.72-0.99] and two
point methods [CV range 1.41-4.62%; ICC range 0.76-0.95], (II) the magnitude of
the same parameters obtained from both methods was highly correlated (r > 0.80),
and (III) the P0 assessed from the multiple-point method was significantly lower
than the obtained from the two-point method [P = 0.041; effect size (ES) 0.36]
due to a significant decrease in F0 (P = 0.039; ES 0.41) with no significant
differences observed for V0 (P = 0.570; ES - 0.15). CONCLUSIONS: These results
support the two-point method as a reliable, valid, and fatigue-free procedure of
assessing the muscle mechanical capacities through the F-V relationship.
PMID- 29946970
TI - In-Vitro Detection of Small Isolated Cartilage Defects: Intravascular Ultrasound
Vs. Optical Coherence Tomography.
AB - This experimental work focused on the sensor selection for the development of a
needle-like instrument to treat small isolated cartilage defects with hydrogels.
The aim was to identify the most accurate and sensitive imaging method to
determine the location and size of defects compared to a gold standard (uCT).
Only intravascular ultrasound imaging (IVUS) vs. optical coherent tomography
(OCT) were looked at, as they fulfilled the criteria for integration in the
needle design. An in-vitro study was conducted on six human cadaveric tali that
were dissected and submerged in saline. To simulate the natural appearance of
cartilage defects, three types of defects were created via a standardised
protocol: osteochondral defects (OCD), chondral defects (CD) and cartilage
surface fibrillation (CSF), all sized between 0.1 and 3 mm in diameter. The
detection rate by two observers for all diameters of OCD were 80, 92 and 100%
with IVUS, OCT and uCT, for CD these were 60, 83 and 97%, and for CSF 0, 29 and
24%. Both IVUS and OCT can detect the presence of OCD and CD accurately if they
are larger than 2 mm in diameter, and OCT can detect fibrillated cartilage
defects larger than 3 mm in diameter. A significant difference between OCT-uCT
and IVUS-uCT was found for the diameter error (p = 0.004) and insertion depth
error (p = 0.002), indicating that OCT gives values closer to reference uCT. The
OCT imaging technique is more sensitive to various types and sizes of defects and
has a smaller diameter, and is therefore preferred for the intended application.
PMID- 29946969
TI - Impact of 60 days of 6 degrees head down tilt bed rest on muscular oxygen uptake
and heart rate kinetics: efficacy of a reactive sledge jump countermeasure.
AB - PURPOSE: The effects of 60 days of head down tilt bed rest (HDBR) with and
without the application of a reactive jump countermeasure were investigated,
using a method which enables to discriminate between pulmonary ([Formula: see
text]O2pulm) and muscular ([Formula: see text]O2musc) oxygen uptake kinetics to
control for hemodynamic influences. METHODS: 22 subjects were randomly allocated
to either a group performing a reactive jumps countermeasure (JUMP; n = 11, male,
29 +/- 7 years, 23.9 +/- 1.3 kg m- 2) or a control group (CTRL; n = 11, male, 29
+/- 6 years, 23.3 +/- 2.0 kg m- 2). Heart rate (HR) and [Formula: see text]O2pulm
were measured in response to repeated changes in work rate between 30 and 80 W
before (BDC-9) and two times after HDBR (R+ 2, R+ 13). Kinetic responses of HR,
[Formula: see text]O2pulm, and [Formula: see text]O2musc were assessed applying
time series analysis. Higher maxima in cross-correlation functions (CCFmax(x))
between work rate and the respective parameter indicate faster kinetics
responses. Statistical analysis was performed applying multifactorial analysis of
variance. RESULTS: CCFmax([Formula: see text]O2musc) and CCFmax([Formula: see
text]O2pulm) were not significantly different before and after HDBR (P > 0.05).
CCFmax(HR) decreased following bed rest (JUMP: BDC-9: 0.30 +/- 0.09 vs. R+ 2:
0.28 +/- 0.06 vs. R+13: 0.28 +/- 0.07; CTRL: 0.35 +/- 0.09 vs. 0.27 +/- 0.06 vs.
0.33 +/- 0.07 P = 0.025). No significant differences between the groups were
observed (P > 0.05). Significant alterations were found for CCFmax of mean
arterial blood pressure (mBP) after HDBR (JUMP: BDC-9: 0.21 +/- 0.07 vs. R+ 2:
0.30 +/- 0.13 vs. R+ 13: 0.28 +/- 0.08; CTRL: 0.25 +/- 0.07 vs. 0.38 +/- 0.13 vs.
0.28 +/- 0.08; P = 0.008). CONCLUSIONS: Despite hemodynamic changes, [Formula:
see text]O2 kinetics seem to be preserved for a longer period of HDBR, even
without the application of a countermeasure.
PMID- 29946972
TI - Trunk Hybrid Passive-Active Musculoskeletal Modeling to Determine the Detailed
T12-S1 Response Under In Vivo Loads.
AB - Biomechanical models of the spine either simplify intervertebral joints (using
spherical joints or deformable beams) in musculoskeletal (MS) or overlook
musculature in geometrically-detailed passive finite element (FE) models. These
distinct active and passive models therefore fail to determine in vivo stresses
and strains within and load-sharing among the joint structures (discs, ligaments,
and facets). A novel hybrid active-passive spine model is therefore developed in
which estimated trunk muscle forces from a MS model for in vivo activities drive
a mechanically-equivalent passive FE model to quantify in vivo T12-S1
compression/shear loads, intradiscal pressures (IDP), centers of rotation (CoR),
ligament/facet forces, and annulus fiber strains. The predicted and in vivo L4-L5
IDP and L1-S1 CoRs showed satisfactory agreements. The FE model under commonly
used in vitro loading (pure moments and follower loads) predicted different
kinetics from those of the hybrid model under in vivo loads (muscle exertions and
gravity loads) contributing to suggest the inadequacy of such in vitro loads when
simulating in vivo tasks. For an improved assessment of the injury risk,
evaluation of the internal loads, and design of implants, such hybrid models
should therefore be used.
PMID- 29946971
TI - Short-Term Contact Kinematic Changes and Longer-Term Biochemical Changes in the
Cartilage After ACL Reconstruction: A Pilot Study.
AB - Investigation of the development of cartilage degeneration after ACL
reconstruction is important for improving current surgical treatment of ACL
injuries to prevent long-term knee joint degeneration. This pilot study examined
the relationship between the changes in weight-bearing knee contact kinematics 6
months after ACL reconstruction and the biochemical composition changes in the
knee cartilage measured using T2 relaxation values 3 years after the surgery in
seven patients. The analysis indicated that the change of the knee contact
kinematics in short-term after ACL reconstruction is associated with an increase
of T2 values of the cartilage in longer follow up times. The data of this study
could provide preliminary data to power future studies that use prospective,
longitudinal research and large patient populations to establish prognostic
biomechanical markers for determination of long-term cartilage degeneration after
ACL reconstruction.
PMID- 29946973
TI - Comparison of Bone Microarchitecture Between Adult Osteogenesis Imperfecta and
Early-Onset Osteoporosis.
AB - Diagnosis and management of adult individuals with low bone mass and increased
bone fragility before the age of 50 can be challenging. A number of these
patients are diagnosed with mild osteogenesis imperfecta (OI) through detection
of COL1A1 or COL1A2 mutations; however, a clinical differentiation from early
onset osteoporosis (EOOP) may be difficult. The purpose of this study was to
determine the bone microstructural differences between mild OI and EOOP patients.
29 patients showed mutations in COL1A1 or COL1A2 and were classified as OI.
Skeletal assessment included dual-energy X-ray absorptiometry (DXA), high
resolution peripheral quantitative computed tomography (HR-pQCT), and bone
turnover serum analyses. Bone microstructure of 21/29 OI patients was assessed
and compared to 23 age- and sex-matched patients clinically classified EOOP but
without mutations in the known disease genes as well as to 20 healthy controls.
In the OI patients, we did not observe an age-dependent decrease in DXA Z-scores.
HR-pQCT revealed a significant reduction in volumetric BMD and microstructural
parameters in the distal radius and tibia in both the OI and EOOP cohorts
compared to the healthy controls. When comparing the bone microstructure of OI
patients with the EOOP cohort, significant differences were found in terms of
bone geometry in the radius, while no significant changes were detected in all
other HR-pQCT parameters at the radius and tibia. Taken together, adult mild OI
patients demonstrate a predominantly high bone turnover trabecular bone loss
syndrome that shows minor microstructural differences compared to EOOP without
mutation detection.
PMID- 29946974
TI - Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in
Swedish Men and Women: A Cross-Sectional Study.
AB - Men and women with type 2 diabetes mellitus (T2DM) have higher risk of hip
fracture, but the mechanisms are not fully understood. We aimed to investigate
how T2DM, glucose, and insulin were associated with femoral bone mineral density
(BMD), bone mineral area (BMA), and bone turnover markers. We used two cross
sectional cohorts: the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 452,
mean age 82 years) and the Swedish Mammography Cohort Clinical (SMCC, n = 4713,
mean age 68 years). We identified men and women with normal fasting glucose
(NFG), impaired fasting plasma glucose (IFG), and T2DM. BMD and BMA at the total
hip and femoral shaft were measured using dual energy X-ray absorptiometry (DXA).
Bone turnover markers; CrossLaps and osteocalcin were measured in women. Linear
regression models were applied. Men and women showed a progressively higher BMD
following the clinical cutoffs of fasting glucose from NFG to IFG to T2DM. In
contrast, there was a progressively lower BMA. Men and women with T2DM, compared
to those with NFG, had lower BMA at the total hip (- 1.7%; 95% CI - 3.2, - 0.2
and - 1.0%; 95% CI - 1.6, - 0.4) and the femoral shaft (- 2.0%; 95% CI - 3.5, -
0.4 and - 0.6%; 95% CI - 1.2, - 0.01), respectively. T2DM was associated with
lower concentrations of CrossLaps (- 8.1%; 95% CI - 12.7, - 3.6) and osteocalcin
(- 15.2%; 95% CI - 19.0, - 11.2). These cross-sectional results indicate that
those with T2DM have smaller bone area and lower bone turnover, which could
increase the risk of hip fracture.
PMID- 29946975
TI - Osseointegration evaluation of laser-deposited titanium dioxide nanoparticles on
commercially pure titanium dental implants.
AB - The nanotechnology field plays an important role in the improvement of dental
implant surfaces. However, the different techniques used to coat these implants
with nanostructured materials can differently affect cells, biomolecules and even
ions at the nano scale level. The aim of this study is to evaluate and compare
the structural, biomechanical and histological characterization of nano titania
films produced by either modified laser or dip coating techniques on commercially
pure titanium implant fixtures. Grade II commercially pure titanium rectangular
samples measuring 35 * 12 * 0.25 mm length, width and thickness, respectively
were coated with titania films using a modified laser deposition technique as the
experimental group, while the control group was dip-coated with titania film. The
crystallinity, surface roughness, histological feature, microstructures and
removal torque values were investigated and compared between the groups. Compared
with dip coating technique, the modified laser technique provided a higher
quality thin coating film, with improved surface roughness values. For in vivo
examinations, forty coated screw-designed dental implants were inserted into the
tibia of 20 white New Zealand rabbits' bone. Biomechanical and histological
evaluations were performed after 2 and 4 weeks of implantation. The histological
findings showed a variation in the bone response around coated implants done with
different coating techniques and different healing intervals. Modified laser
coated samples revealed a significant improvement in structure, surface roughness
values, bone integration and bond strength at the bone-implant interface than dip
coated samples. Thus, this technique can be an alternative for coating titanium
dental implants.
PMID- 29946976
TI - Preparation and characterization of metal-substituted carotenoid cleavage
oxygenases.
AB - Carotenoid cleavage oxygenases (CCO) are non-heme iron enzymes that catalyze
oxidative cleavage of alkene bonds in carotenoid and stilbenoid substrates.
Previously, we showed that the iron cofactor of CAO1, a resveratrol-cleaving
member of this family, can be substituted with cobalt to yield a catalytically
inert enzyme useful for trapping active site-bound stilbenoid substrates for
structural characterization. Metal substitution may provide a general method for
identifying the natural substrates for CCOs in addition to facilitating
structural and biophysical characterization of CCO-carotenoid complexes under
normal aerobic conditions. Here, we demonstrate the general applicability of
cobalt substitution in a prototypical carotenoid cleaving CCO, apocarotenoid
oxygenase (ACO) from Synechocystis. Among the non-native divalent metals
investigated, cobalt was uniquely able to stably occupy the ACO metal binding
site and inhibit catalysis. Analysis by X-ray crystallography and X-ray
absorption spectroscopy demonstrate that the Co(II) forms of both ACO and CAO1
exhibit a close structural correspondence to the native Fe(II) enzyme forms.
Hence, cobalt substitution is an effective strategy for generating catalytically
inert but structurally intact forms of CCOs.
PMID- 29946977
TI - The chemical biology and coordination chemistry of putrebactin, avaroferrin,
bisucaberin, and alcaligin.
AB - Dihydroxamic acid macrocyclic siderophores comprise four members: putrebactin
(putH2), avaroferrin (avaH2), bisucaberin (bisH2), and alcaligin (alcH2). This
mini-review collates studies of the chemical biology and coordination chemistry
of these macrocycles, with an emphasis on putH2. These Fe(III)-binding
macrocycles are produced by selected bacteria to acquire insoluble Fe(III) from
the local environment. The macrocycles are optimally pre-configured for Fe(III)
binding, as established from the X-ray crystal structure of dinuclear [Fe2(alc)3]
at neutral pH. The dimeric macrocycles are biosynthetic products of two endo
hydroxamic acid ligands flanked by one amine group and one carboxylic acid group,
which are assembled from 1,4-diaminobutane and/or 1,5-diaminopentane as initial
substrates. The biosynthesis of alcH2 includes an additional diamine C
hydroxylation step. Knowledge of putH2 biosynthesis supported the use of
precursor-directed biosynthesis to generate unsaturated putH2 analogues by
culturing Shewanella putrefaciens in medium supplemented with unsaturated diamine
substrates. The X-ray crystal structures of putH2, avaH2 and alcH2 show
differences in the relative orientations of the amide and hydroxamic acid
functional groups that could prescribe differences in solvation and other
biological properties. Functional differences have been borne out in biological
studies. Although evolved for Fe(III) acquisition, solution coordination
complexes have been characterised between putH2 and oxido-V(IV/V), Mo(VI), or
Cr(V). Retrosynthetic analysis of 1:1 complexes of [Fe(put)]+, [Fe(ava)]+, and
[Fe(bis)]+ that dominate at pH < 5 led to a forward metal-templated synthesis
approach to generate the Fe(III)-loaded macrocycles, with apo-macrocycles
furnished upon incubation with EDTA. This mini-review aims to capture the rich
chemistry and chemical biology of these seemingly simple compounds.
PMID- 29946978
TI - beta-Hydroxyaspartic acid in siderophores: biosynthesis and reactivity.
AB - A growing number of siderophores are found to contain beta-hydroxyaspartic acid
(beta-OH-Asp) as a functional group for Fe(III) coordination, along with the more
common catechol and hydroxamic acid groups. This review covers the structures,
biosynthesis, and reactions of peptidic beta-OH-Asp siderophores. Hydroxylation
of Asp in siderophore biosynthesis is predicted to be carried out either through
discrete aspartyl beta-hydroxylating enzymes or through hydroxylating domains
within non-ribosomal peptide synthetases, both of which display sequence homology
to known non-heme iron(II), alpha-ketoglutarate-dependent dioxygenases. Ferric
complexes of beta-OH-Asp siderophores are photoreactive, resulting in reduction
of Fe(III) and oxidative cleavage of the siderophore to yield distinct types of
photoproducts. Probing the photoreactivity of synthetic Fe(III)-alpha
hydroxycarboxylate clusters yields mechanistic insights into the different
photoproducts observed for beta-OH-Asp and other alpha-hydroxycarboxylate
siderophore Fe(III) complexes.
PMID- 29946979
TI - Upon further analysis, neither cytochrome c554 from Nitrosomonas europaea nor its
F156A variant display NO reductase activity, though both proteins bind nitric
oxide reversibly.
AB - A re-investigation of the interaction with NO of the small tetraheme protein
cytochrome c554 (C554) from Nitrosomonas europaea has shown that the 5-coordinate
heme II of the two- or four-electron-reduced protein will nitrosylate reversibly.
The process is first order in C554, first order in NO, and second-order overall.
The rate constant for NO binding to the heme is 3000 +/- 140 M-1s-1, while that
for dissociation is 0.034 +/- 0.009 s-1; the degree of protein reduction does not
appear to significantly influence the nitrosylation rate. In contrast to a
previous report (Upadhyay AK, et al. J Am Chem Soc 128:4330, 2006), this study
found no evidence of C554-catalyzed NO reduction, either with [Formula: see text]
or with [Formula: see text] Some sub-stoichiometric oxidation of the lowest
potential heme IV was detected when [Formula: see text] was exposed to an excess
of NO, but this is believed to arise from partial intramolecular electron
transfer that generates {Fe(NO)}8 at heme II. The vacant heme II coordination
site of C554 is crowded by three non-bonding hydrophobic amino acids. After
replacing one of these (Phe156) with the smaller alanine, the nitrosylation rate
for F156A2- and F156A4- was about 400* faster than for the wild type, though the
rate of the reverse denitrosylation process was almost unchanged. Unlike in the
wild-type C554, the 6-coordinate low-spin hemes of F156A4- oxidized over the
course of several minutes after exposure to NO. Concomitant formation of N2O
could explain this heme oxidation, though alternative explanations are equally
plausible given the available data.
PMID- 29946980
TI - Ether cross-link formation in the R2-like ligand-binding oxidase.
AB - R2-like ligand-binding oxidases contain a dinuclear metal cofactor which can
consist either of two iron ions or one manganese and one iron ion, but the
heterodinuclear Mn/Fe cofactor is the preferred assembly in the presence of MnII
and FeII in vitro. We have previously shown that both types of cofactor are
capable of catalyzing formation of a tyrosine-valine ether cross-link in the
protein scaffold. Here we demonstrate that Mn/Fe centers catalyze cross-link
formation more efficiently than Fe/Fe centers, indicating that the
heterodinuclear cofactor is the biologically relevant one. We further explore the
chemical potential of the Mn/Fe cofactor by introducing mutations at the cross
linking valine residue. We find that cross-link formation is possible also to the
tertiary beta-carbon in an isoleucine, but not to the secondary beta-carbon or
tertiary gamma-carbon in a leucine, nor to the primary beta-carbon of an alanine.
These results illustrate that the reactivity of the cofactor is highly specific
and directed.
PMID- 29946982
TI - Correction to: Pyruvate Kinase M2 Increases Angiogenesis, Neurogenesis, and
Functional Recovery Mediated by Upregulation of STAT3 and Focal Adhesion Kinase
Activities after Ischemic Stroke in Adult Mice.
AB - The original version of this article was updated to correct the misspelling of Li
Ping Liu's name.
PMID- 29946981
TI - Targeted-Plasticity in the Corticospinal Tract After Human Spinal Cord Injury.
AB - Spinal cord injury (SCI) often results in impaired or absent sensorimotor
function below the level of the lesion. Recent electrophysiological studies in
humans with chronic incomplete SCI demonstrate that voluntary motor output can be
to some extent potentiated by noninvasive stimulation that targets the
corticospinal tract. We discuss emerging approaches that use transcranial
magnetic stimulation (TMS) over the primary motor cortex and electrical
stimulation over a peripheral nerve as tools to induce plasticity in residual
corticospinal projections. A single TMS pulse over the primary motor cortex has
been paired with peripheral nerve electrical stimulation at precise interstimulus
intervals to reinforce corticospinal synaptic transmission using principles of
spike-timing dependent plasticity. Pairs of TMS pulses have also been used at
interstimulus intervals that mimic the periodicity of descending indirect (I)
waves volleys in the corticospinal tract. This data, along with information about
the extent of the injury, provides a new framework for exploring the contribution
of the corticospinal tract to recovery of function following SCI.
PMID- 29946983
TI - A multivariate examination of 'artificial mussels' in conjunction with spot water
tests in freshwater ecosystems.
AB - Metal pollution in aquatic systems is considered a serious environmental issue
globally due to their ability to accumulate in aquatic environments. Wetlands are
vulnerable to this pollution as they are known to trap toxins, removing them from
the water. Artificial mussel technology, originally developed for marine
environments, was applied to this freshwater system and spot water samples were
collected. The Nyl River floodplain (Ramsar classified) is one of the largest and
most ecologically significant wetlands in South Africa. The aims of this study
were to determine metal contamination along the Nyl River system by means of
artificial mussels (AM) and water ICP-MS analysis and to determine whether the
use of AMs in conjunction with spot water testing could give more insight into
the pollution in freshwater wetlands. The concentrations of Al, Cd, Cr, Co, Cu,
Fe, Mn, Ni, Pb and Zn were determined at seven sites. It was determined that the
levels accumulated by the AMs differed in spatial and temporal trends when
compared to spot water samples. It was determined that there were high levels of
some metals found in the spot water tests that were not corroborated by the AMs
results, which could indicate isolated pollution events. The use of AMs in
conjunction with spot water testing was determined to be beneficial in gaining
deeper insight into water metal conditions in dynamic freshwater systems.
PMID- 29946984
TI - Use of Cyclodextrin as a Novel Agent in the SEC-HPLC Mobile Phase to Mitigate the
Interactions of Proteins or Peptide or their Impurities with the Residual
Silanols of Commercial SEC-HPLC Columns with Improved Separation and Resolution.
AB - PURPOSE: Accurate quantification of the intact proteins, antibodies or peptides
and their impurities without interaction to silanols of HPLC column. METHODS:
Hydroxypropyl beta Cyclodextrin (HPCD) is added in the mobile phase at different
concentrations. Different commercial SEC-HPLC columns and biologics with a
molecular weight ranging from 5.8 kDa to 150kDa were assessed with and without
cyclodextrin. RESULTS: Addition of non-ionic sugars such as Hydroxypropyl beta
Cyclodextrin in the mobile phase, resulted improved peak performance such as
theoretical plates, peak resolution, peak width, peak height, and improved
quantification of aggregates in biologics such as antibodies Humira and Actemra,
and peptides such as insulin. There is an increase in peak height, reduced
retention time, increased plate and reduced peak width with increasing
concentration of cyclodextrin studied. DISCUSSION: High ionic strength, basic
amino acids such as arginine, organic solvents (with a concentration low enough
not to precipitate protein), sodium perchlorate and ion pairing agents in the
mobile phase used for separation of peptides, proteins and antibodies to prevent
silanol interaction. These commonly used solutions are not always successful, as
they not only interact with the biologic, but are sometimes, not compatible. The
non-ionic cyclodextrin itself does not cause protein aggregation but prevents the
nonspecific binding or interaction of protein itself and thereby allowing for
improved resolution, and accurate quantification of aggregates in antibodies, and
peptides. The data on the separation in presence of cyclodextrin in the mobile
phase showed higher peak resolution, improved peak shape, accurate apparent
molecular weight, improved efficiency, and less peak tailing for biological
products. CONCLUSION: Hydroxypropyl beta Cyclodextrin in the mobile phase,
resulted improved SEC-HPLC resolution, and quantitation of aggregates in
biologics by preventing the interaction of biologics to silanol of the commercial
SEC-HPLC columns.
PMID- 29946985
TI - First molecular epidemiological study of Mycobacterium avium subsp.
paratuberculosis in cattle and buffalo from different regions of Brazil.
AB - Paratuberculosis is an incurable disease in ruminants with great worldwide
economic impact, caused by Mycobacterium avium subsp. paratuberculosis (MAP). The
objective of this study was to carry out a study of the molecular epidemiology of
the MAP using the restriction enzyme analysis (REA) technique of IS1311 MAP
region in biological samples of feces, intestinal tissue, and mesenteric lymph
nodes of cattle and buffaloes from six Brazilian states. In total, 109 samples of
feces and tissues of cattle and buffaloes were collected from animal
paratuberculosis suspected. Twenty-five samples were positive in the detection of
the DNA of the IS900 region of MAP and it was possible to type 18 strains in the
analysis of the region IS1311, being 100% of them identified as belonging to
subtype Bison MAP strain. This is the first epidemiological molecular study of
MAP in Brazil. The results indicate that paratuberculosis is widespread in cattle
and in buffaloes in several regions of Brazil, and the subtype Bison MAP strain
was the only one identified in the samples analyzed in this study, demonstrating
the similarity between the strains from different states tested. These results
provide the necessary support for the implementation of paratuberculosis control
strategies in cattle and buffaloes in Brazil.
PMID- 29946986
TI - Modern pollen distribution in the northeastern Indian Ocean and its significance.
AB - In order to provide a reference for reconstructing the paleoclimate of the
northeastern Indian Ocean, 36 airborne pollen samples were analyzed using methods
for airborne pollen, and 26 surface water samples were analyzed using a lab
method for surface water. We found that little pollen is airborne over the Indian
Ocean in spring, but airborne pollen types and concentrations can help to deduce
paleomonsoon strength and direction. The conclusions included the following: (1)
Pollen in the sediment was transported mainly via ocean currents instead of the
early summer or spring wind. (2) Airborne pollen types and concentrations are
proportional to the wind speed and inversely proportional to the pollen distance
transported and depend on whether the wind is from the land or from the sea. If
the wind is from the land, the pollen concentration is proportional to the angle
between the wind direction and the coastline. (3) The pollen concentration in the
sample collected from a water depth of 30-45 m is higher than in the samples
collected from a depth of 5 m. The pollen concentration and salinity are higher
in the equatorial area than in the Northern Hemisphere.
PMID- 29946987
TI - Pleiotropic roles of O-mannosyltransferase MoPmt4 in development and
pathogenicity of Magnaporthe oryzae.
AB - In fungi, O-mannosylation is one type of conserved protein modifications that add
the carbohydrate residues to specific residues of target proteins by protein O
mannosyltransferases. Previously, three members of O-mannosyltransferases were
identified in Magnaporthe oryzae, with MoPmt2 playing important roles in fungal
growth and pathogenicity. However, the biological roles of the rest Pmt proteins
remain unclear. In this study, to understand if O-mannosyltransferases are
crucial for fungal pathogenicity of M. oryzae, the Pmt-coding genes MoPmt1 and
MoPmt4 were separately disrupted and their roles in pathogenesis were analyzed.
Of the two genes, only MoPmt4 is specifically required for full virulence of M.
oryzae. Deletion of MoPmt4 resulted in defects on radial growth, with more
branching hyphae and septa as compared to Guy11. The MoPmt4 mutant was severely
impaired not only in conidiation, but also in both penetration and biotrophic
invasion in susceptible rice plants. This mutant also had defects in suppression
of host-derived ROS-mediated plant defense responses that might be ascribed from
the reduced activities of extracellular enzymes. Furthermore, like their fungi
counterparts, MoPmt4 localized in the ER and had O-mannosyltransferase activity.
Domain disruption analysis indicated that mannosyltransferase activity regulated
by PMT domain of MoPmt4 is crucial for fungal development and pathogenicity of M.
oryzae. Taken together, these data suggest that MoPmt4 is a protein O
mannosyltransferase essential for fungal development and full virulence of M.
oryzae.
PMID- 29946988
TI - Study on the expressions of NLRP3 gene transcript variants in peripheral blood
monocytes of primary gout patients.
AB - It is well-known that NLRP3 is closely related to the onset of primary gout (PG).
However, the relation between NLRP3 gene transcript variants and the occurrence
of PG remains unclear. This study was undertaken to evaluate whether NLRP3 gene
transcript variants are involved in the occurrence of PG. A total of 44 acute
phase PG (APPG), 52 non-acute phase PG (NAPPG) male patients, and 30 male health
control (HC) were involved in this study. We measured NLRP3 and its transcript
variants 2, 3, 4, 5, and 1 + 6 expressions in the PBMCs, together with the level
of IL-1beta in the serum. Further, PBMCs of HC were stimulated with MSU crystals.
The levels of NLRP3, NLRP3 gene transcript variants 2, 3, 4 mRNA, and protein
expressions were significantly lower in the APPG and NAPPG groups than in the HC
group (P < 0.05, respectively), and IL-1beta expression was significantly higher
in the APPG group than in the HC and NAPPG groups (P < 0.05, respectively).
Levels of IL-1beta and NLRP3-4 mRNA expressions were negatively correlated with
APPG group (r = - 0.2828, P = 0.0252). After stimulating PBMCs of HC with MSU
crystals, levels of NLRP3, NLRP3-4 mRNA, and NLRP3 protein expressions were
reduced significantly (P < 0.05, respectively), and the level of IL-1beta in MSU
group was increased significantly (P < 0.05). Here, we show that NLRP3-4
transcript variant may be closely related to the occurrence of PG. Thus, NLRP3-4
gene transcript variant may provide a novel target for the diagnosis and therapy
of PG.
PMID- 29946989
TI - Clinical characteristics and bisphosphonates treatment of rare pregnancy- and
lactation-associated osteoporosis.
AB - Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disorder with
poorly known etiology, pathophysiology, and therapy. We aimed to investigate the
clinical characteristics of PLO and evaluate the effectiveness and safety of
bisphosphonates on it. A total of 12 patients were diagnosed with PLO on the
basis of medical history, bone mineral density (BMD), and/or fragility fractures
during pregnancy and lactation. We investigated the clinical, biochemical, and
radiological characteristics of patients. We assessed the effects of alendronate
or zoledronic acid through observing the changes of bone turnover biomarkers and
BMD during the treatment. Secondary osteoporosis was excluded by comprehensive
differential diagnosis. The mean age of these patients was 31 +/- 5 years old.
All of these patients presented severe back pain. Multiple vertebral compression
fractures (VCFs) were found in 10 patients, and the median (P25th, P75th) number
of compressed vertebra was 3 (3, 5). Ten patients had vitamin D insufficiency or
deficiency. Serum level of bone resorption marker (beta-CTX with mean of 0.68 +/-
0.41 ng/ml) was moderately higher than the normal range. BMD at lumbar spine,
femoral neck, and total hip were low as 0.894 +/- 0.153 g/cm2, 0.728 +/- 0.090
g/cm2, and 0.728 +/- 0.080 g/cm2, respectively. Either alendronate or zoledronic
acid could effectively relieve bone pain, reduce beta-CTX level, and increase
BMD. PLO is a rare type of osteoporosis, which was characterized by increased
bone resorption and decreased BMD, even VCFs. Bisphosphonate therapy was well
tolerated and effective in management of PLO, but needed to be further verified
in randomized controlled trial.
PMID- 29946990
TI - Genome-wide association study of body weight in Wenshang Barred chicken based on
the SLAF-seq technology.
AB - Chicken body weight (BW) is an economically important trait, and many studies
have been conducted on genetic selection for BW. However, previous studies have
detected functional chromosome mutations or regions using gene chips. The present
study used the specific-locus amplified fragment sequencing (SLAF-seq) technology
to perform a genome-wide association study (GWAS) on purebred Wengshang Barred
chicken. A total of 1,286,715 single-nucleotide polymorphisms (SNPs) were
detected, and 175,211 SNPs were selected as candidate SNPs for genome-wide
association analysis using TASSEL general linear models. Six SNP markers reached
genome-wide significance. Of these, rs732048524, rs735522839, rs738991545, and
rs15837818 were significantly associated with body weight at 28 days (BW28),
while rs314086457 and rs315694878 were significantly associated with BW120. These
SNPs are close to seven genes (PRSS23, ME3, FAM181B, NABP1, SDPR, TSSK6L2, and
RBBP8). Moreover, 24 BW-associated SNPs reached "suggestive" genome-wide
significance. Of these, 6, 13, 1, and 4 SNPs were associated with BW28, BW56,
BW80, and BW120, respectively. These results would enrich the studies on BW and
promote the use of Chinese chicken, especially the Wenshang Barred chicken.
PMID- 29946991
TI - Hyaluronic acid-grafted three-dimensional MWCNT array as biosensing interface for
chronocoulometric detection and fluorometric imaging of CD44-overexpressing
cancer cells.
AB - A sandwich-type electrochemical cytosensor is described for quantitative
determination of CD44-overexpressing HeLa cells. Hyaluronic acid (HA) acts as a
targeting molecule that was in-situ incorporated into the sensor based on the use
of an indium tin oxide (ITO) electrode modified with multi-walled carbon
nanotubes (MWCNTs). The 3D-MWCNT structure is shown to strongly improve the
electronic properties and surface chemical reactivities. The HA-modified sensor
exhibits a highly sensitive response to HeLa cells. A sandwiched hybridization
protocol was then established using BIO [an N-butyl-4-(6'-aminohexyl)amino-1,8
naphthalimide probe modified with HA] as the tracing labels of the fluorescent
probes for targeting CD44-positive tumor cells. The signal amplification was
thereby maximized and measured by chronocoulometry. The binding of CD44-positive
HeLa cells to the HA modified sensing layer causes a decrease in
chronocoulometric response. The signal decreases linearly in the 2.1 * 102 to 2.1
* 107 HeLa cells.mL-1 concentration range with a detection limit of 70 cells.mL
1. Such a sandwich-type assay may be tailored as a sensitive candidate for
detecting low levels of tumor cells. Graphical abstract Schematic of a sandwich
cytosensor based on hyaluronic acid-grafted 3D-MWCNT as biosensing interface and
BIO as fluorescent probe. This biosensor possessed excellent electrochemical
activity, high sensitivity and selectivity, providing a dynamical tracking and
detecting platform for CD44-positive tumor cells.
PMID- 29946992
TI - Unravelling the effect of macro and microscopic design of dental implants on
osseointegration: a randomised clinical study in minipigs.
AB - Several dental implants are commercially available and new prototype design are
constantly being fabricated. Nevertheless, it is still unclear what parameters of
the design affect most the osseointegration of dental implants. The purpose of
this study is to assess the effects of the microscopic and macroscopic design of
dental implants in the osseointegration by comparing three macroscopic designs
(Straumann tissue level (STD), essential cone (ECD) and prototype design (PD))
and six surface treatments. A total of 96 implants were placed in 12 minipigs.
The implant stability quotient (ISQ), was assessed at the time of implantation,
as well as at 2, 4 and 8 weeks. Histomorphometric and statistical analyses were
conducted at the different sacrifice times, being 2, 4 and 8 weeks, to analyse
the bone to implant contact (BIC), the bone area density (BAT) and the density of
bone outside the thread region (ROI). The macroscopic design results showed
higher ISQ values for the ECD, whereas the histomorphometric analysis showed
higher ossoeintegration values for the STD. Regarding the microscopic design,
both Sandblasted plus acid etching (hydrochloric/sulphuric acid) in a nitrogen
atmosphere (SLActive) and Shot-blasted or bombarded with alumina particles and
posterior alkaline immersion and thermal treatment (ContacTi) showed superior
results in terms of osseointegration and reduced the osseointegration times from
8 weeks to 4 weeks compared to the other analysed surfaces. In conclusion, each
of the macroscopic and microscopic designs need to be taken into account when
designing novel dental implants to enhance the osseointegration process.
PMID- 29946993
TI - Antimicrobial properties of ternary eutectic aluminum alloys.
AB - Several Escherichia coli deletion mutants of the Keio collection were selected
for analysis to better understand which genes may play a key role in copper or
silver homeostasis. Each of the selected E. coli mutants had a deletion of a
single gene predicted to encode proteins for homologous recombination or
contained functions directly linked to copper or silver transport or
transformation. The survival of these strains on pure copper surfaces, stainless
steel, and alloys of aluminum, copper and/or silver was investigated. When
exposed to pure copper surfaces, E. coli DeltacueO was the most sensitive,
whereas E. coli DeltacopA was the most resistant amongst the different strains
tested. However, we observed a different trend in sensitivities in E. coli
strains upon exposure to alloys of the system Al-Ag-Cu. While minor antimicrobial
effects were detected after exposure of E. coli DeltacopA and E. coli DeltarecA
to Al-Ag alloys, no effect was detected after exposure to Al-Cu alloys. The
release of copper ions and cell-associated copper ion concentrations were
determined for E. coli DeltacopA and the wild-type E. coli after exposure to pure
copper surfaces. Altogether, compared to binary alloys, ternary eutectic alloys
(Al-Ag-Cu) had the highest antimicrobial effect and thus, warrant further
investigation.
PMID- 29946994
TI - Acute pain intensity monitoring with the classification of multiple physiological
parameters.
AB - Current acute pain intensity assessment tools are mainly based on self-reporting
by patients, which is impractical for non-communicative, sedated or critically
ill patients. In previous studies, various physiological signals have been
observed qualitatively as a potential pain intensity index. On the basis of that,
this study aims at developing a continuous pain monitoring method with the
classification of multiple physiological parameters. Heart rate (HR), breath rate
(BR), galvanic skin response (GSR) and facial surface electromyogram were
collected from 30 healthy volunteers under thermal and electrical pain stimuli.
The collected samples were labelled as no pain, mild pain or moderate/severe pain
based on a self-reported visual analogue scale. The patterns of these three
classes were first observed from the distribution of the 13 processed
physiological parameters. Then, artificial neural network classifiers were
trained, validated and tested with the physiological parameters. The average
classification accuracy was 70.6%. The same method was applied to the medians of
each class in each test and accuracy was improved to 83.3%. With facial
electromyogram, the adaptivity of this method to a new subject was improved as
the recognition accuracy of moderate/severe pain in leave-one-subject-out cross
validation was promoted from 74.9 +/- 21.0 to 76.3 +/- 18.1%. Among healthy
volunteers, GSR, HR and BR were better correlated to pain intensity variations
than facial muscle activities. The classification of multiple accessible
physiological parameters can potentially provide a way to differentiate among no,
mild and moderate/severe acute experimental pain.
PMID- 29946995
TI - Subcutaneous Phaeohyphomycosis Caused by Exophiala oligosperma in an
Immunocompetent Host: Case Report and Literature Review.
AB - We report a case of subcutaneous infection caused by Exophiala oligosperma.
Erythematous ulcerated plaque with exudate was major clinical features.
Histopathological examination showed yeast-like cells and fungal hyphae.
Mycological and molecular identification revealed E. oligosperma as etiologic
agent. Local debridement and oral itraconazole were effective. To the best of our
knowledge, this is the first report of phaeohyphomycosis caused by E. oligosperma
in mainland China. This report highlights the potential role of E. oligosperma as
an emerging cause of infection in immunocompetent patients.
PMID- 29946996
TI - Putting It All Together to Understand the Role of Malassezia spp. in Dandruff
Etiology.
AB - Dandruff is a common scalp condition causing both a discomfort and an undesired
social image. Various studies dating from early 1900s have investigated the
condition, but understanding of underlying mechanisms and etiology of the
condition is still in its infancy. Formation of dandruff is a common but complex
event which has been associated with numerous causal factors. Physiological
conditions such as pH, water content, or sebum secretion are some of the host
related factors. An imbalance between these factors can disturb the physiological
equilibrium of the scalp that can lead to dandruff formation. However, severity
of the condition is strongly related to the lipophilic yeast of the skin
microbiota, Malassezia spp. On the other hand, there are recent publications
highlighting the role of other scalp microbiota members on dandruff formation.
This review investigates the processes leading to the formation of dandruff to
provide an etiological description of the condition, with a focus on Malassezia
spp.
PMID- 29946998
TI - Editorial Comment to "Robotic-Assisted Surgery for Upper Tract Urothelial
Carcinoma: A Comparative Survival Analysis".
PMID- 29946997
TI - Outcomes and Treatment Options for Duodenal Adenocarcinoma: A Systematic Review
and Meta-Analysis.
AB - BACKGROUND: Duodenal adenocarcinoma (DA) is a rare tumor for which survival data
per treatment modality and disease stage are unclear. This systematic review and
meta-analysis aims to summarize the current literature on patient outcome after
surgical, (neo)adjuvant, and palliative treatment in patients with DA. METHODS: A
systematic search was performed according to the preferred reporting items for
systematic reviews and meta-analyses guidelines, to 25 April 2017. Primary
outcome was overall survival (OS), specified for treatment strategy or disease
stage. Random-effects models were used for the calculation of pooled odds ratios
per treatment modality. Included papers were also screened for prognostic
factors. RESULTS: A total of 26 observational studies, comprising 6438 patients
with DA, were included. Of these, resection with curative intent was performed in
71% (range 53-100%) of patients, and 29% received palliative treatment (range 0
61%). The pooled 5-year OS rate was 46% after curative resection, compared with
1% in palliative-treated patients (OR 0.04, 95% confidence interval [CI] 0.02
0.09, p < 0.0001). Both segmental resection and pancreaticoduodenectomy allowed
adequate assessment of lymph node involvement and resulted in similar OS. Lymph
node involvement correlated with worse OS (pooled 5-year survival rate 21% for
nodal metastases vs. 65% for node-negative disease; OR 0.17, 95% CI 0.11-0.27, p
< 0.0001). In the current literature, no survival benefit for adjuvant therapy
after curative resection was found. CONCLUSION: Resection with curative intent,
either pancreaticoduodenectomy or segmental resection, and lack of nodal
metastases, favors survival for DA. Further studies exploring multimodality
(neo)adjuvant therapy are warranted to investigate their benefit.
PMID- 29946999
TI - MelMART Trial: It's Now or Never.
PMID- 29947000
TI - Presidential Address: Surgeons as Advocates-A Time for Action.
PMID- 29947001
TI - Multidisciplinary Intraoperative Assessment of Breast Specimens Reduces Number of
Positive Margins.
AB - BACKGROUND: Successful breast-conserving surgery requires achieving negative
margins. At our institution, the whole surgical specimen is imaged and then
serially sectioned with repeat imaging. A multidisciplinary discussion then
determines need for excision of additional margins. The goal of this study was to
determine the benefit of each component of this approach in reducing the number
of positive margin. METHODS: This single-institution, prospective study included
ten breast surgical oncologists who were surveyed to ascertain whether they would
have taken additional margins based their review of whole specimen images (WSI)
and review of serially sectioned images (SSI). These results were compared with
the multidisciplinary decisions (MDD) and pathology results. Margin status was
defined using consensus guidelines. RESULTS: One hundred surveys were completed.
Margins on the original specimen were positive or close in 21%. After WSI,
surgeons reported that they would have taken additional margins in 26 cases,
reducing the number of positive/close margins from 21 to 13% (p < 0.001). After
SSI, 52 would have taken additional margins; however, the number of
positive/close margins remained 13%. MDD resulted in additional margins taken in
56 cases, reducing the number of positive/close margins to 7% (p < 0.001 compared
with SSI). CONCLUSIONS: While surgeon review of specimen radiographs can decrease
the number of positive or close margins from 21 to 13%, more rigorous
multidisciplinary, intraoperative margin assessment reduces the number of close
or positive margins to 7%.
PMID- 29947002
TI - Should Reexcision Rates in Breast Cancer Care be a Quality Measure?
PMID- 29947003
TI - Correction to: 1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous
Melanoma (MelMarT): A Feasibility Study.
AB - In the original article John F. Thompson was inadvertently omitted as an author.
The author list is updated as shown in this correction.
PMID- 29947004
TI - Treatment Outcomes for Pleomorphic Lobular Carcinoma In Situ of the Breast.
AB - BACKGROUND: Pleomorphic lobular carcinoma in situ (PLCIS) is an uncommon high
grade in situ lesion that shares morphologic features of both classic lobular and
ductal carcinoma in situ. Data on the natural history of pure PLCIS are limited,
and no evidence-based consensus guidelines for management exist. METHODS: From
our prospectively maintained institutional pathology and breast surgery
databases, we identified all patients with a diagnosis of PLCIS on core needle
biopsy (CNB) or excisional biopsy from 2004 to 2017. Patient, tumor, treatment,
and outcome data were abstracted to analyze upstage rates and treatment outcomes.
RESULTS: We identified 18 patients with pure PLCIS: 15 diagnosed on CNB, 2
diagnosed at operation for atypia on CNB, and 1 diagnosed after excisional biopsy
without preceding CNB. Of the 15 patients with PLCIS on CNB, 3 (20%) were
upgraded to invasive cancer on surgical excision. Overall, 7 patients were
treated with mastectomy (all margin-negative) and 11 with lumpectomy (one with a
focally positive margin). Eight patients received adjuvant therapy: six endocrine
therapy, one radiation therapy, and one received both. Among patients with a
final diagnosis of PLCIS, two ipsilateral recurrences were observed at follow-up:
one invasive lobular carcinoma at 87 months and one PLCIS at 16 months
postoperatively. CONCLUSION: PLCIS on CNB mandates surgical resection as 20% of
patients may be upgraded to invasive cancer, and outcomes following pathologic
margin-negative surgical resection were excellent with only one invasive
recurrence observed. Larger-scale investigation with longer follow-up is needed
to define a role for adjuvant therapy and to develop evidence-based treatment
guidelines.
PMID- 29947005
TI - Management of In-Breast Tumor Recurrence.
AB - The management of isolated in-breast tumor recurrence is complex, requiring
careful consideration of prior local therapies to plan future multimodality
treatment. Options for surgical management have evolved from standard salvage
mastectomy with axillary clearance and now include repeat breast conservation
with axillary staging in select patients. Reattempting sentinel lymph node biopsy
may avoid the morbidity of extensive axillary surgery and has been shown to be
feasible in clinically node-negative patients with oncologically safe outcomes.
In the adjuvant setting, partial breast irradiation has emerged as a valuable
means to improve local control rates with limited associated toxicity and
acceptable overall cosmesis. Furthermore, results from prospective trials are now
available to support the use of chemotherapy in hormone-receptor negative
subgroups, which is associated with improvements in long-term, disease-free, and
overall survival.
PMID- 29947006
TI - Quality of Life and Body Image as a Function of Time from Mastectomy.
AB - BACKGROUND: We sought to determine the impact of time after surgery on quality of
life (QoL) and body image in breast cancer patients undergoing mastectomy.
METHODS: Female patients with unilateral breast cancer who had undergone
mastectomy were surveyed regarding their body image (Body Image After Breast
Cancer Questionnaire; BIBCQ) and QoL (FACT-B). Data were analyzed using
nonparametric statistics (SPSS version 24). RESULTS: Ninety-four of the 109
patients approached completed both surveys (86.2% response rate). Median patient
age at the time of surgery was 49.5 (range 29-82); the survey was administered at
a median of 14.2 months postoperatively (range 0.3-192.1 months). Seventy-four
patients (78.7%) had reconstruction, and 52 patients (55.3%) chose to undergo
contralateral prophylactic mastectomy. Patients who reported an above average
overall body image perception on the BIBCQ tended to be further out from their
surgery than those who reported a below average perception (median 20.9 vs. 8.1
months, respectively, p = 0.009). Patients who reported above average QoL also
tended to be further out from their surgery compared with those with below
average overall QoL (median 21.8 vs. 6.4 months, respectively, p = 0.004).
Receipt of reconstruction, contralateral prophylactic mastectomy, disease stage,
patient race, education, insurance type, income, marital status, employment
status, and age at surgery did not significantly affect body image nor QoL in
this cohort. CONCLUSIONS: Better body image perception and higher QoL were
associated with being further out from surgery. These findings suggest that body
image and QoL may improve with time, as patients acclimatize to their "new
normal."
PMID- 29947007
TI - Scratching the Surface of Psychiatric Services Distribution and Public Health: an
Indiana Assessment.
AB - Mental illness is a leading cause of disability with many public health
implications. Previous studies have demonstrated a national shortage of
psychiatrists, particularly in rural areas. An analysis of how this workforce
distribution relates to population demographics and public/behavioral health is
lacking in the literature. This study encompassed a statewide assessment of the
Indiana psychiatric workforce as it relates to population characteristics and
public/behavioral health. This study's findings demonstrate a profoundly low
psychiatry workforce in rural counties of Indiana. The low psychiatry workforce
capacity in rural counties is so disparate that the demographic and
public/behavioral health characteristics differ from the State averages in the
same manner as counties without a psychiatrist at all. The psychiatric workforce
distribution did not differ significantly on the basis of poverty prevalence. The
potential utility of indicators of population health was also evaluated and
revealed that social factors such as poverty and Medicaid prevalence may be
superior to more traditional measures.
PMID- 29947008
TI - Identification of cervical cancer using laser-induced breakdown spectroscopy
coupled with principal component analysis and support vector machine.
AB - Cervical cancer is one of the most widespread diseases in women. Traditional
cancer diagnosis is extremely complicated and relies on subjective interpretation
of biopsy material. In this work, laser-induced breakdown spectroscopy (LIBS) was
used in cervical cancer recognition. In order to improve identification accuracy
of cervical cancer by LIBS, the chemometric methods of principal component
analysis (PCA) and support vector machine (SVM) were combined. The results show
that the content of trace elements in normal tissues and cervical cancer tissues
was significantly different. Normalized peak intensities of Na, Mg, and K in the
cervical cancer tissues were significantly higher than normal tissues, and the
normalized peak intensities of Ca in the normal tissues were higher than cervical
cancer tissues. The identification accuracies of PCA-SVM are better than SVM,
with the achieved accuracies of 94.44% and 93.06%, respectively. It can be
concluded that LIBS techniques coupled with chemometric method is a potential in
cancer tissue identification, which provides a preliminary research basis for
real-time diagnosis of cancer tissues using LIBS.
PMID- 29947009
TI - Thulium (Tm:YAG) laser vaporesection of prostate and bipolar transurethral
resection of prostate in patients with benign prostate hyperplasia: a systematic
review and meta-analysis.
AB - Thulium laser vaporesection (ThuVARP) and bipolar transurethral resection of the
prostate (B-TURP) are novel surgeries for benign prostate hyperplasia (BPH). This
paper is a systematic review and analysis of literatures comparing efficacy
indicators, operative parameters, as well as safety indicators between ThuVARP
and B-TURP for the treatment of BPH. A systematic search of electronic databases,
including PubMed, the Cochrane Library, Web of Science, Embase, and China
National Knowledge Internet (CNKI), was carried out up to December 1, 2015
(updated on March 1, 2016). The captivating outcomes included basic clinical
characteristics, perioperative parameters, local complications, and efficacy
indicators which included International Prostate Symptom Score (IPSS), quality of
life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR). After
assessing the quality of methodology and extracting data, a meta-analysis was
carried out by using STATA 12.0 software. Five studies involving 500 patients met
the standard. The outcomes of this analysis were as follows: (a) efficacy
indicators: there were no significant differences in IPSS, QoL, PVR, and Qmax
between the two groups (all P > 0.05); (b) perioperative indicators: ThuVARP had
longer operative time [standardized mean difference (SMD) = 0.843; 95% confidence
interval (CI) - 0.391, 1.296; P < 0.001] but less serum hemoglobin decreased (SMD
= - 0.561; 95% CI - 0.796, - 0.327; P < 0.001), shorter hospital stay (SMD = -
1.558; 95% CI - 2.709, - 0.407; P < 0.01), and catheterization time (SMD = -
1.274; 95% CI - 2.158, - 0.390; P < 0.01). Additionally, no significant
difference was found in estimated resected weight (P > 0.05); (c) safety
indicators: no significant difference was found in local complication rates (all
P > 0.05) between ThuVARP and B-TURP. In our analysis, there exists no
statistical difference between ThuVARP and B-TURP group in efficacy. However, in
spite of requiring longer surgical time, ThuVARP was better in terms of less
blood loss as well as shorter hospitalization and catheterization time.
PMID- 29947010
TI - Impact of viral hepatitis B status on outcomes of intrahepatic
cholangiocarcinoma: a meta-analysis.
AB - BACKGROUND AND AIMS: To estimate the impact of viral hepatitis B status on
outcomes of intrahepatic cholangiocarcinoma. METHODS: We searched Pubmed and
Embase for original articles that evaluated the impact of hepatitis B virus
infection on outcomes of intrahepatic cholangiocarcinoma. The present study was
conducted to generate odd ratios (ORs) with 95% confidence intervals (CIs) for
pre-identified prognostic factors, overall survival, and recurrence. RESULTS:
From 438 studies, we identified eight articles that compared outcomes between
hepatitis B virus-infected patients and the others. In terms of
clinicopathological characteristics, patients in the hepatitis B virus group
significantly demonstrated single nodular tumor (OR 0.7; 95% CI 0.5-0.9; p =
0.01), infrequent lymph node metastasis (OR 0.5; 95% CI 0.3-0.6; p < 0.01), and
infrequent perineural infiltration (OR 0.3; 95% CI 0.2-0.8; p < 0.01). No
significant between-group differences were found in tumor diameter, vascular
invasion, and tumor differentiation. Previous or temporary infection
(seropositivity for hepatitis B core antibody) revealed no significant impact on
clinicopathological characteristics. For survival outcomes, meta-analysis
demonstrated that hepatitis B virus group had significantly better overall
survival, recurrence rate, and median survival (p < 0.01). CONCLUSIONS: Our
results suggest that hepatitis B virus infection is a powerful predictor of
favorable survival outcomes for intrahepatic cholangiocarcinoma and significantly
affects clinicopathological characteristics. Viral hepatitis B status needs to be
taken into account and then establish therapeutic approaches.
PMID- 29947011
TI - Antioxidant Rich Potato Improves Arterial Stiffness in Healthy Adults.
AB - Arterial stiffness is an emerging risk factor for cardiovascular disease and
dietary anthocyanins may be important in mediating vascular tone. The present
study investigated the effect of consumption of an anthocyanin-rich potato,
Purple Majesty on arterial stiffness measured as pulse wave velocity in 14
healthy male and female adults. Participants consumed 200 g/day of cooked purple
potato containing 288 mg anthocyanins, or a white potato containing negligible
anthocyanins for 14 days, separated by a 7-day washout period. Non-invasive
assessment of vascular tone by pulse wave velocity was determined in addition to
systolic and diastolic blood pressure, high-density lipoproteins, low-density
lipoproteins, triglycerides, glucose, insulin and C-reactive protein. Pulse wave
velocity was significantly reduced (p = 0.001) following Purple Majesty
consumption for 14-days. There were no significant changes with any other
clinical parameter measured, and no changes following white potato consumption.
The findings from this short-term study indicate a potential effect of Purple
Majesty consumption on arterial stiffness.
PMID- 29947012
TI - Proliferative CD8(+) PD-1(+) T-cell infiltration in a pembrolizumab-induced
cutaneous adverse reaction.
AB - Pembrolizumab, a humanized monoclonal immunoglobulin (Ig) G4 antibody that is
directed against the human cell surface receptor PD-1, is a PD-1 pathway
inhibitor that has been approved to treat various malignant diseases, including
advanced non-small cell lung cancer (NSCLC). PD-1 is the major inhibitory
receptor regulating T-cell exhaustion, and T-cells with high PD-1 expression lose
their ability to eliminate cancer. PD-1 pathway blockade by pembrolizumab
reinvigorates exhausted T-cells and restores their antitumor immune responses.
However, reinvigorated T-cells also evoke immune-related adverse effects (irAEs),
which stem from the restored activity. Currently, the pathogenic mechanisms of
irAEs have not been sufficiently determined. We experienced a patient with NSCLC
with high PD-L1 expression and cervical lymph node metastases, who demonstrated a
good clinical response to first line pembrolizumab but suffered from a severe
cutaneous adverse event. Both of his skin lesions and cervical metastases showed
extensive CD8(+) PD-1(+) T-cell infiltration in immunofluorescence analysis. This
finding suggests a possible contribution of reinvigorated CD8(+) PD-1(+) T-cells
in anti-PD-1 therapy-induced skin rash. Intriguingly, CD8(+) T-cells in the skin
rash showed higher Ki-67 expression, a proliferation marker, than those in the
cervical lymph node lesion. This is the first report of an association between
proliferative CD8(+) PD-1(+) T-cells and irAEs.
PMID- 29947013
TI - Inhibition of SHP2 by new compounds induces differential effects on RAS/RAF/ERK
and PI3K/AKT pathways in different cancer cell types.
AB - Kinases and phosphatases are important players in growth signaling and are
involved in cancer development. For development of targeted cancer therapy,
attention is given to kinases rather than phosphatases inhibitors. Src homology
region 2 domain-containing protein tyrosine phosphatase2 (SHP2) is overexpressed
in different types of cancers. We investigated the SHP2-inhibitory effects of two
new 5-aminosalicylate-4-thiazolinones in human cervical (HeLa) and breast (MCF-7
& MDA-MB-231) cancer cells. In-silico molecular docking showed preferential
affinity of the two compounds towards the catalytic over the allosteric site of
SHP2. An enzymatic assay confirmed the docking results whereby 0.01 MUM of both
compounds reduced SHP2 activity to 50%. On cellular level, the two compounds
significantly reduced the expression of SHP2, KRAS, p-ERK and p-STAT3 in HeLa but
not in the other two cell lines. Phosphorylation of AKT and JNK was enhanced in
HeLa and MCF7. Both compounds exhibited anti-proliferative/anti-migratory effects
on HeLa and MCF7 but not in MDA-MB-231 cells. These results indicate that
inhibition of SHP2 and its downstream pathways by the two compounds might be a
promising strategy for cancer therapy in some but not all cancer types.
PMID- 29947015
TI - Effect of antitubercular treatment on the pregnancy outcomes and prognoses of
patients with genital tuberculosis.
AB - This retrospective study aims to demonstrate the effect of antitubercular
treatment (ATT) on the pregnancy outcomes and prognoses of patients with genital
tuberculosis (GTB) who had received laparoscopy and/or hysteroscopy. This study
included 78 patients with infertility and who were diagnosed with GTB through
laparoscopy and/or hysteroscopy over the period of November 2005 to October 2015.
The recruited patients were divided into ATT and nonATT groups on the basis of
ATT duration. The GTB recurrence rates, menstrual patterns, and pregnancy
outcomes of the patients were determined at follow-up. Among the 78 patients, 46
received ATT and 32 did not receive ATT. The menstrual volumes of patients in the
ATT group significantly decreased relative to those of patients in the nonATT
group. GTB did not recur among all patients regardless of treatment. A total of
11 pregnancies (36.7%) in the ATT group and 19 pregnancies (63.3%) in the nonATT
group were observed. Pregnancy rates significantly differed (P = 0.002) between
the two groups. ATT may decrease the menstrual volume and pregnancy rates of
patients who were diagnosed with GTB through laparoscopy and/or hysteroscopy. In
addition, ATT did not improve the prognosis of patients with chronic GTB.
PMID- 29947016
TI - A Shape Memory Alloy-Based Miniaturized Actuator for Catheter Interventions.
AB - In the current scenario of endovascular intervention, surgeons have to manually
navigate the catheter within the complex vasculature of the human body under the
guidance of X-ray. This manual intervention upsurges the possibilities of vessel
damage due to frequent contact between the catheter and vasculature wall. In this
context, a shape memory alloy-based miniaturized actuator was proposed in this
study with a specific aim to reduce vessel wall related damage by improving the
bending motions of the guidewire tip in a semi-automatic fashion. The
miniaturized actuator was integrated with a FDA-approved guidewire and tested
within a patient-specific vascular network model to realize its feasibility in
the real surgical environment. The results illustrate that the miniaturized
actuator gives a bending angle over 23 degrees and lateral displacement over 900
um to the guide wire tip by which the guidewire can be navigated with precision
and possible vessel damage during the catheter intervention can certainly be
minimized. In addition to it, the dynamic responses of the presented actuator
were further investigated through numerical simulation in conjunction with the
analytic analysis.
PMID- 29947014
TI - Lauric Acid Alleviates Neuroinflammatory Responses by Activated Microglia:
Involvement of the GPR40-Dependent Pathway.
AB - In several neurodegenerative diseases such as Alzheimer's disease (AD), microglia
are hyperactivated and release nitric oxide (NO) and proinflammatory cytokines,
resulting its neuropathology. Mounting evidence indicates that dietary
supplementation with coconut oil (CNO) reduces the cognitive deficits associated
with AD; however, the precise mechanism(s) underlying the beneficial effect of
CNO are unknown. In the present study, we examined the effects of lauric acid
(LA), a major constituent of CNO, on microglia activated experimentally by
lipopolysaccharide (LPS), using primary cultured rat microglia and the mouse
microglial cell line, BV-2. LA attenuated LPS-stimulated NO production and the
expression of inducible NO synthase protein without affecting cell viability. In
addition, LA suppressed LPS-induced reactive oxygen species and proinflammatory
cytokine production, as well as phosphorylation of p38-mitogen activated protein
kinase and c-Jun N-terminal kinase. LA-induced suppression of NO production was
partially but significantly reversed in the presence of GW1100, an antagonist of
G protein-coupled receptor (GPR) 40, which is an LA receptor on the plasma
membrane. LA also decreased LPS-induced phagocytosis, which was completely
reversed by co-treatment with GW1100. Moreover, LA alleviated amyloid-beta
induced enhancement of phagocytosis. These results suggest that attenuation of
microglial activation by LA may occur via the GPR40-dependent pathway. Such
effects of LA may reduce glial activation and the subsequent neuronal damage in
AD patients who consume CNO.
PMID- 29947018
TI - Increased odds of disordered eating in polycystic ovary syndrome: a systematic
review and meta-analysis.
AB - PURPOSE: We aimed to identify the risk of eating disorders (ED) in women with
polycystic ovary syndrome (PCOS) compared to controls. METHODS: We performed a
systematic review and meta-analysis of studies that included women with well
defined PCOS and controls and used validated ED screening/diagnostic tools to
measure mean ED score, prevalence of abnormal ED scores, and/or prevalence of
specific ED diagnoses such as bulimia nervosa and binge eating disorder. RESULTS:
Eight studies, including 470 women with PCOS and 390 controls, met inclusion
criteria for the systematic review. Meta-analysis of seven of those studies found
that the odds of an abnormal ED score (OR 3.05; 95% CI 1.33, 6.99; four studies)
and the odds of any ED diagnosis (OR 3.87; 95% CI 1.43, 10.49; four studies) were
higher in women with PCOS compared to controls. CONCLUSIONS: Our study suggests
that women with PCOS are at increased odds of having abnormal ED scores and
specific ED diagnoses. Given the potential implications of an ED on weight
management strategies, our findings support routine screening for ED in this
population. LEVEL OF EVIDENCE: Level I, systematic review and meta-analysis.
PMID- 29947017
TI - Executive functioning and psychological symptoms in food addiction: a study among
individuals with severe obesity.
AB - Food addiction (FA) has recently emerged as a new field in the study of obesity.
Previous studies have contributed to identifying psychological correlates of FA.
However, few researchers have examined the cognitive profile related to this
condition; up until now, attentional biases related to food cues and a poorer
performance monitoring have been observed. The present study aimed to examine the
psychological profile and executive functioning related to FA in individuals with
severe obesity and awaiting bariatric surgery. Participants (N = 86) were split
into two groups, according to their level of FA symptoms (low FA vs high FA).
Groups were compared on questionnaires measuring binge eating, depression and
anxiety symptoms, and impulsivity as well as on measures reflecting executive
functioning (D-KEFS and BRIEF-A). The relationship between FA groups and patterns
of errors during the D-KEFS' Color-Word Interference Test was further analyzed.
Individuals within the high FA group reported significantly more binge eating,
depressive and anxiety symptoms, and more metacognitive difficulties. They also
tended to show a poorer inhibition/cognitive flexibility score and a typical
pattern of errors, characterized by an increased number of errors as the tasks'
difficulty rose as opposed to a decreased number of errors, which characterizes
an atypical pattern of errors. The present results show that the inability to
learn from errors or past experiences is related to the severity of FA and
overall impairments.Level of evidence Level V, descriptive study.
PMID- 29947019
TI - Nanogel-mediated delivery of a cocktail of epigenetic drugs plus doxorubicin
overcomes drug resistance in breast cancer cells.
AB - Epigenetic modifications (e.g., DNA methylation or histone deacetylation) are
commonly implicated in cancer chemoresistance. We previously showed that
pretreating resistant MCF-7/ADR breast cancer cells with a demethylating agent (5
aza-2'-deoxycytidine (DAC)) or with an inhibitor of histone deacetylase
(suberoylanilide hydroxamic acid (SAHA)) sensitized resistant cells to
doxorubicin (DOX) treatment. However, even with increasing doses of DOX, a
fraction of resistant cells remained nonresponsive to this pretreatment (~ 25%
pretreated with DAC, ~ 45% with SAHA). We hypothesized that pretreating resistant
cells with a combination of epigenetic drugs (DAC + SAHA) could more effectively
overcome drug resistance. We postulated that delivery of epigenetic drugs
encapsulated in biodegradable nanogels (NGs) would further enhance their
efficacy. MCF-7/ADR cells were first treated with a single drug vs. a combination
of epigenetic drugs, either as solutions or encapsulated in NGs, then subjected
to DOX, either in solution or in NGs. Antiproliferative data showed that
pretreatment with epigenetic drugs in NGs, then with DOX in NGs, was most
effective in overcoming resistance; this treatment inhibited cell growth by >
90%, even at low doses of DOX. Cell cycle analysis showed that a major fraction
of cells treated with a cocktail of epigenetic drugs + DOX, all in NG
formulations, remained in the G2/M cell cycle arrest phase for a prolonged
period. The mechanism of better efficacy of epigenetic drugs in NGs could be
attributed to their sustained effect. A similar strategy could be developed for
other cancer cells in which drug resistance is due to epigenetic modifications.
PMID- 29947021
TI - Roller compaction: the effect of plastic deformation of primary particles with
wide range of mechanical properties.
AB - Understanding the compaction behaviour of the primary powder in the roller
compaction process is necessary to be able to better control the quality of the
product. In this study, the plastic deformation of the primary particles was
evaluated by determining two mechanical properties: the nano-indentation hardness
and the viscoelasticity of the primary powder. The nano-indentation hardness of
eight different materials with a wide range of mechanical properties was
determined by indenting the surface of the single primary particle, whereas the
viscoelasticity was evaluated for a powder bed using the creep test. These were
linked to fundamental ribbon properties such as ribbon strength and width in
addition to the amount of fines. It was identified that the plastic deformation
of the material had the potential to provide an indication for the ability of the
primary powder to produce a good ribbon. For the range of the investigated
process parameters, the optimum hardness range that produced ribbons with ideal
properties and small amount of fines was suggested.
PMID- 29947020
TI - Intra-articular delivery of a nanocomplex comprising salmon calcitonin,
hyaluronic acid, and chitosan using an equine model of joint inflammation.
AB - Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT),
chitosan (CS), and hyaluronic acid (HA) were previously established as having
anti-inflammatory potential when injected via the intra-articular (i.a.) route to
a mouse model. We attempted to translate the formulation to a large animal model,
the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The
aim was to manufacture under aseptic conditions to produce sterile pyrogen-free
NPs, to confirm physicochemical characteristics, and to test toxicity and
efficacy in a pilot study. NP dispersions were successfully formulated using
pharmaceutical-grade source materials and were aseptically manufactured under GMP
simulated conditions in a grade A modular aseptic processing workstation. The NP
formulation had no detectable pathogen or endotoxin contamination. NPs were then
tested versus a lactated Ringer's solution control following single i.a.
injections to the radiocarpal joints of two groups of four horses pre-treated
with LPS, followed by arthrocentesis at set intervals over 1 week. There was no
evidence of treatment-related toxicity over the period. While there were no
differences between clinical read-outs of the NP and the control, two synovial
fluid-derived biomarkers associated with cartilage turnover revealed a beneficial
effect of NPs. In conclusion, NPs comprising well-known materials were
manufactured for an equine i.a.-injectable pilot study and yielded no NP
attributable toxicity. Evidence of NP-associated benefit at the level of
secondary endpoints was detected as a result of decreases in synovial fluid
inflammatory biomarkers.
PMID- 29947022
TI - Skin structure in newborn marsupials with focus on cutaneous gas exchange.
AB - A morphological and morphometric study of the skin of a variety of newborn
marsupials (Dasyurus viverrinus, Monodelphis domestica, Trichosurus vulpecula,
Isoodon obesulus, Perameles nasuta, Phascolarctos cinereus, Potorous tridactylus,
Petrogale penicillata, Thylogale thetidi, Macropus dorsalis) and of a monotreme
hatchling (Ornithorhynchus anatinus) was undertaken to assess the possibility of
cutaneous gas exchange. Additionally, the lungs of some of these species were
investigated to assess its structural degree at birth. The skin in the different
newborn marsupials and the monotreme hatchling had a similar structure (no hair
follicles and no sebaceous or perspiratory glands) and was in all cases less
developed than the skin of altricial eutherians. The thickness of the entire skin
(36-186 MUm) and its different layers, epidermis (6-29 MUm) and dermis (29-171
MUm) varied among the marsupial species and reflected the differences in size and
developmental degree of the neonates. In the skin of all marsupial neonates and
the monotreme hatchling, numerous superficial cutaneous capillaries were
encountered, some closely associated with the epidermis, indicating the
possibility that the skin participated in gaseous exchange. The skin of the
newborn D. viverrinus had the highest capillary volume density and shortest skin
diffusion barrier of all marsupial neonates, suggesting that skin gas exchange in
the dasyurid neonate might be the most pronounced. A graduation of the skin
capillary density among the marsupial neonates inversely followed the respective
lung structure and general developmental degree of the neonates.
PMID- 29947023
TI - Rebuttal from Luc J. Teppema.
PMID- 29947024
TI - The role of parenting experiences, rather than age of onset or presence of the
skin condition, in the development of early maladaptive schemas in a community
sample of patients with atopic dermatitis.
PMID- 29947025
TI - A retrospective study of lichen planus pigmentosus with focus on palmoplantar
involvement.
AB - Lichen planus pigmentosus (LPP) is a rare disease characterized by persistent and
asymptomatic slate-grey pigmentation, which mostly affects patients with skin
types IV-VI. The face and neck are the most commonly involved sites, followed by
the trunk and extremities. LPP is believed to spare the palms, soles and nails.
In this report, we describe palmoplantar involvement in 10 (4.65%, 10/215)
patients with LPP, and compare its clinicodemographic features with those of
classic LPP. LPP lesions on the palms and soles present as asymptomatic, well
circumscribed, hyperpigmented, brown-black patches without any history of prior
lichen planus lesions. They are mostly observed in young patients with rapidly
spreading active disease, who often require systemic treatment to control the
disease activity. Strikingly, palmoplantar involvement is frequently associated
with other atypical LPP variants. It is important to identify palmoplantar
involvement in LPP, as it has a different clinical course and associations
compared with classic LPP.
PMID- 29947026
TI - Computer-assisted analysis of tongue thickness of golden hamster (Mesocricetus
auratus) following topical chronic exposure to distilled alcoholic beverages.
AB - The aim of this study was to measure changes in epithelial thickness in the
lingual mucosa of golden hamsters submitted to the topical application of
distilled alcoholic beverages. Forty golden hamsters were randomly divided into:
Group 1-cachaca 48 degrees GL and Group 2-whisky 40 degrees GL. Alcohol was
applied to the right side of the tongue, the left side served as control. Seventy
microscopic fields were evaluated. The data were submitted to descriptive
statistics, the Wilcoxon test and the Mann-Whitney U test (p < 0.05). In Group 1,
there was a significant difference in mean total epithelial thickness between the
test side and control side (p = 0.044), with significant reductions in the
thickness of the epithelial and corneal layers (p < 0.001 and p = 0.021,
respectively). At 13 weeks, statistically significant reductions were found in
the thickness of both the corneal and epithelial layers (p = 0.032 and p < 001,
respectively). At 20 weeks, a statistically significant reduction was found in
only the epithelial layer (p = 0.002). In the whisky group, significant increases
were found in the thickness of the corneal and epithelial layers (p = 0.015 and p
= 0.012, respectively) at 13 weeks. Cachaca 48 degrees GL promoted epithelial
atrophy, whereas whisky 40 degrees GL promoted epithelial hyperplasia. Based on
the present findings, different types of distilled alcoholic beverages cause
different morphometric and morphological changes in the lingual mucosa. Cachaca
caused epithelial atrophy, which may facilitate the penetration of carcinogenic
agents, whereas whisky caused epithelial hyperplasia, especially in the basal
layer, which suggests the onset of the development of premalignant lesions.
PMID- 29947027
TI - Fabrication and characterization of implantable flushable electrodes for electric
field-mediated drug delivery in a brain tissue-mimic agarose gel.
AB - Every forty minutes, one person dies in the USA due to glioblastoma multiforme; a
deadly form of brain cancer with an average five-year survival rate less than 3%.
The current standard of care for treatment involves surgical resection of the
accessible tumor followed by radiation therapy and concomitant chemotherapy.
Despite their potency, delivering chemotherapeutic agents to the brain is limited
by the highly selective blood-brain barrier, which prevents molecules >500 Da
from reaching the brain. Other techniques, such as convection-enhanced delivery,
controlled release by drug-loaded wafers or intracerebroventricular infusion have
limited clinical utility due to unpredictable targeting and volume of drug
distribution. We introduce a novel drug delivery technique that can use direct
current electric fields to deliver charged chemotherapeutics to the site of brain
parenchyma after tumor resection. We fabricate and characterize an implantable
drug delivery system using flushable electrodes to deliver the charged
chemotherapeutic or doxorubicin (+1) in a brain tissue-mimic agarose gel (0.2%
w/v) model by electrophoresis. The optimized capillary-embedded electrode system
exhibited a sustained movement of charged doxorubicin through nearly 3.5 mm in
four hours, a distance for achieving effective intratumoral concentrations.
PMID- 29947028
TI - Antimicrobial endotoxin-neutralizing peptides promote keratinocyte migration via
P2X7 receptor activation and accelerate wound healing in vivo.
AB - BACKGROUND AND PURPOSE: Wound healing is a complex process that is essential to
provide skin homeostasis. Infection with pathogenic bacteria such as
Staphylococcus aureus can lead to chronic wounds, which are challenging to heal.
Previously, we demonstrated that the antimicrobial endotoxin-neutralizing peptide
Pep19-2.5 promotes artificial wound closure in keratinocytes. Here, we
investigated the mechanism of peptide-induced cell migration and if Pep19-2.5
accelerates wound closure in vivo. EXPERIMENTAL APPROACH: Cell migration was
examined in HaCaT keratinocytes and P2X7 receptor-overexpressing HEK293 cells
using the wound healing scratch assay. The protein expression of phosphorylated
ERK1/2, ATP release, calcium influx and mitochondrial ROS were analysed to
characterize Pep19-2.5-mediated signalling. For in vivo studies, female BALB/c
mice were wounded and infected with methicillin-resistant S. aureus (MRSA) or
left non-infected and treated topically with Pep19-2.5 twice daily for 6 days.
KEY RESULTS: Specific P2X7 receptor antagonists inhibited Pep19-2.5-induced cell
migration and ERK1/2 phosphorylation in keratinocytes and P2X7 receptor
transfected HEK293 cells. ATP release was not increased by Pep19-2.5; however,
ATP was required for cell migration. Pep19-2.5 increased cytosolic calcium and
mitochondrial ROS, which were involved in peptide-induced migration and ERK1/2
phosphorylation. In both non-infected and MRSA-infected wounds, the wound
diameter was reduced already at day 2 post-wounding in the Pep19-2.5-treated
groups compared to vehicle, and remained decreased until day 6. CONCLUSIONS AND
IMPLICATIONS: Our data suggest the potential application of Pep19-2.5 in the
treatment of non-infected and S. aureus-infected wounds and provide insights into
the mechanism involved in Pep19-2.5-induced wound healing.
PMID- 29947029
TI - Right atrial thrombus entrapped in a Chiari's network.
PMID- 29947031
TI - Ketone-Functionalized Polymer Nano-Objects Prepared via Photoinitiated
Polymerization-Induced Self-Assembly (Photo-PISA) Using a Poly(diacetone
acrylamide)-Based Macro-RAFT Agent.
AB - Herein, ketone-functionalized diblock copolymer nano-objects are prepared by
photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion
polymerization of tert-butyl acrylate (tBA) using a poly(diacetone acrylamide)
(PDAAM)-based macromolecular RAFT (macro-RAFT) agent in ethanol/water (60/40,
w/w) at room temperature. A high polymerization rate is observed via the exposure
of visible light (lambdamax = 405 nm, 0.45 mW cm-2 ) with near quantitative
monomer conversion being achieved within 60 min. A morphological phase diagram is
constructed by changing the degree of polymerization (DP) of PtBA and the monomer
concentration. The morphologies of polymer nano-objects are further tuned by
incorporating isobornyl acrylate (IBOA) into the core-forming block. The ketone
functionalized diblock copolymer nano-objects can be shell-cross-linked by
reacting with a diamine. Finally, the shell-cross-linked polymer nano-objects are
further hydrolyzed and employed as a template for the synthesis of silver
composites.
PMID- 29947030
TI - AHNS Series: Do you know your guidelines? AHNS Endocrine Section Consensus
Statement: State-of-the-art thyroid surgical recommendations in the era of
noninvasive follicular thyroid neoplasm with papillary-like nuclear features.
AB - The newly introduced pathologic diagnosis of noninvasive follicular thyroid
neoplasm with papillary-like nuclear features (NIFTP) will result in less
bilateral thyroid surgery as well as deescalation in T4 suppressive and
radioactive iodine treatment. Although, NIFTP is a nonmalignant lesion that has
nuclear features of some papillary malignancies, the challenge for the surgeon is
to identify a lesion as possibly NIFTP before the pathologic diagnosis. NIFTP,
due to its reduction of overall rates of malignancy, will result in the initial
surgical pendulum swinging toward lobectomy instead of initial total
thyroidectomy. This American Head and Neck Society endocrine section consensus
statement is intended to inform preoperative evaluation to attempt to identify
those patients whose final pathology report may ultimately harbor NIFTP and can
be offered a conservative surgical plan to assist in cost-effective, optimal
management of patients with NIFTP.
PMID- 29947032
TI - Identification and preliminary study of immunogens involved in autoimmune
prostatitis in human males.
AB - BACKGROUND: Experimental models have confirmed that autoimmunity is an important
factor in the onset of chronic prostatitis/chronic pelvic pain syndrome
(CP/CPPS); however, there is no conclusive evidence on whether autoimmune
prostatitis exists in human males. METHODS: Rabbits were immunized with either
human prostate tissue homogenates or normal saline and the antiserum was
collected. Two-dimensional electrophoresis (2-DE) was performed on the
homogenates and Western blotting was conducted on the sera. The identified human
prostate tissue immunodominant antigens (HPTIAs) were detected by mass
spectrometry. The serum immunoglobulin (Ig)G from the immunized rabbits was
purified with protein A-agarose, and the purified IgG was linked with Sepharose
to purify HPTIAs by affinity chromatography. Non-obese diabetic (NOD) mice were
immunized with the purified HPTIAs, and the levels of serum antibodies, INF
gamma, and histopathological changes in their prostate tissues were detected. The
purified HPTIAs were coated into polystyrene pores and serum autoantibodies in
CP/CPPS patients were detected by enzyme-linked immunosorbent assay (ELISA).
Meanwhile, serum interleukin 2 (IL-2), interferon gamma (IFNgamma), and tumor
necrosis factor alpha (TNFalpha) levels in CP/CPPS patients were also determined
by ELISA. RESULTS: Sixteen HPTIAs were identified. Among them, three types were
reported to be associated with prostatic diseases. Prostatitis was induced in
mice immunized with the 16-HPTIA complex, with positive serum autoantibody and
increased prostatic IFN-gamma levels. The positive rate of serum autoantibodies
against HPTIAs was significantly higher in CP/CPPS patients (23.1%, 18/78) than
in the control (2.7%, 2/75). But there was no significant difference in serum
TNFalpha, IFNgamma, and IL-2 levels between the CPPS patients with positive and
negative autoantibodies against HPTIAs. CONCLUSIONS: Autoantibodies against
HPTIAs exist in part in CP/CPPS patients, which implies that autoimmunity and the
16 HPTIAs are important factors in the onset of CP/CPPS. The detection of serum
autoantibodies could be applied in clinical diagnoses of autoimmune prostatitis;
treatment protocols might change. Additional studies are needed to determine
which of the 16 HPTIAs is the most important.
PMID- 29947033
TI - Early impact of the ICD-10-CM transition on selected health outcomes in 13
electronic health care databases in the United States.
AB - PURPOSE: To describe the consistency in the frequency of 5 health outcomes across
the International Classification of Diseases, Ninth Revision, Clinical
Modification (ICD-9-CM) and Tenth Revision, Clinical Modification (ICD-10-CM)
eras in the US. METHODS: We examined the incidence of 3 acute conditions (acute
myocardial infarction [AMI], angioedema, ischemic stroke) and the prevalence of 2
chronic conditions (diabetes, hypertension) during the final 5 years of the ICD-9
CM era (January 2010-September 2015) and the first 15 months of the ICD-10-CM era
(October 2015-December 2016) in 13 electronic health care databases in the
Sentinel System. For each health outcome reviewed during the ICD-10-CM era, we
evaluated 4 definitions, including published algorithms derived from other
countries, as well as simple-forward, simple-backward, and forward-backward
mapping using the General Equivalence Mappings. For acute conditions, we also
compared the incidence between April to December 2014 and April to December 2016.
RESULTS: The analyses included data from approximately 172 million health plan
members. While the incidence or prevalence of AMI and hypertension performed
similarly across the 2 eras, the other 3 outcomes did not demonstrate consistent
trends for some or all the ICD-10-CM definitions assessed. CONCLUSIONS: When
using data from both the ICD-9-CM and ICD-10-CM eras, or when using results from
ICD-10-CM data to compare to results from ICD-9-CM data, researchers should test
multiple ICD-10-CM outcome definitions as part of sensitivity analysis. Ongoing
assessment of the impact of ICD-10-CM transition on identification of health
outcomes in US electronic health care databases should occur as more data accrue.
PMID- 29947035
TI - Adding to the mounting evidence for geographic inequity in liver transplantation:
Hospital length of stay.
AB - BACKGROUND: Severe geographic inequities in liver transplantation have persisted
for years. Previous investigators have demonstrated 90-day transplant rates
varying from 14% to 82% and death rates varying from 18% to 86%. The aim of this
analysis was to utilize a robust multivariate analysis to investigate whether
geographic inequities affected the length of stay after liver transplantation.
METHODS: We conducted a unique Kaplan-Meier analysis with the event being
discharge from the hospital and length of stay as the time to the event, using a
cohort of 66 674 recipients listed in the UNOS database from 2002 to 2016.
Multivariate Cox regression using 43 covariates was used for time-to-event
analysis. RESULTS: Region 9 (0.82; CI 0.79-0.85), Region 2 (0.85; CI 0.83-0.88),
and Region 10 (0.96; CI 0.93-0.99) were statistically significant factors for
prolonged hospital stay. The following covariates were the most significant
factors for prolonged hospital stay: serum sodium >150 mEq/L (0.70; CI 0.62
0.78), ICU admission (0.77; CI 0.74-0.80), hospital admission (0.81; 0.79-0.83),
region 9 (0.82; CI 0.79-0.85), and ventilator dependence (0.82; CI 0.76-0.88).
CONCLUSION: In this analysis, we demonstrate regional disparities in hospital
length of stay that are significant in robust multivariable Cox regression
analysis. We hope the transplant community will take immediate measures to
correct geographic inequities.
PMID- 29947034
TI - Carbon and nitrogen isotope variability in the seeds of two African millet
species: Pennisetum glaucum and Eleusine coracana.
AB - RATIONALE: A range of important small seeded C4 crops were domesticated in
Africa, but little is known about their carbon and nitrogen isotope ratios
(delta13 C and delta15 N values). Understanding natural isotopic variability
within and among millets has the potential to help us to understand the
conditions under which ancient cereals were grown and has significant
implications for the interpretation of ancient diets based on stable isotope
signatures. METHODS: We conducted carbon and nitrogen isotope analyses of modern
and historical pearl millet (Pennisetum glaucum, n = 108) and finger millet
(Eleusine coracana, n = 17) seed samples sourced from the United States
Department of Agriculture as well as the Harlan Collection curated at the Crop
Evolution Laboratory Herbarium at the University of Illinois. RESULTS: The millet
species have significantly different mean carbon and nitrogen isotope ratios over
broad temporal and spatial scales. We also found substantial isotopic variation
within species (range of 1.90/00 and 8.50/00 in delta13 C and delta15 N values,
respectively). Both water availability and growing season temperature
significantly affected the P. glaucum delta13 C and delta15 N values; cumulative
annual precipitation was positively correlated with both seed delta13 C and
delta15 N values, while temperature was positively correlated with delta15 N
values but negatively correlated with seed delta13 C values. CONCLUSIONS: The
importance of both temperature and precipitation as predictors of delta13 C and
delta15 N values in millets suggests that C4 plants may be more sensitive to
environmental parameters than previously appreciated. Given the high degree of
carbon and nitrogen isotope variability among accessions of these species, it is
imperative that site-relevant plant isotope ratios are used for making isotope
based paleo-dietary predictions.
PMID- 29947036
TI - Ultra-Bright Rhodamines with Sulfobutylether-beta-Cyclodextrin: A Viable
Supramolecular Dye Laser in Aqueous Medium.
AB - Although aqueous dye lasers are much sought after, they have been of no practical
use, as laser dyes show a strong tendency for aggregation in water, thus
diminishing their optical output. Contributing towards this shortcoming, we
studied the noncovalent interactions of two prominent laser dyes, namely,
rhodamine 6G and rhodamine B, with a water soluble macrocyclic host,
sulfobutylether-beta-cyclodextrin (SBE7 betaCD). Spectral changes in the
absorption and fluorescence behavior of dyes in presence of the SBE7 betaCD host
indicated adequate complex formation between dye and host (K~104 M-1 ). A
combination of various photophysical parameters evaluated from measurements such
as Job plot, changes in the fluorescence lifetime/anisotropy values, and
favorable thermodynamic parameters from isothermal titration calorimetric
measurements adjudicated a 1 : 1 stoichiometric complex formation between dye and
SBE7 betaCD host. Consequently, SBE7 betaCD prevents dye aggregation/adsorption
and present rhodamine dyes in their monomeric forms with enhanced fluorescence
yield and brightness. These vital parameters were utilized to optimize and
demonstrate cost-effective supramolecular broad-band and narrow-band aqueous dye
laser systems with improved lasing efficiencies (~25 % higher for the SBE7 betaCD
: RhB system and ~10 % higher for SBE7 betaCD : Rh6G system), better beam
profile, and enhanced durability compared to the respective dyes in optically
matched ethanol solutions.
PMID- 29947037
TI - Animacy and real-world size shape object representations in the human medial
temporal lobes.
AB - Identifying what an object is, and whether an object has been encountered before,
is a crucial aspect of human behavior. Despite this importance, we do not yet
have a complete understanding of the neural basis of these abilities.
Investigations into the neural organization of human object representations have
revealed category specific organization in the ventral visual stream in
perceptual tasks. Interestingly, these categories fall within broader domains of
organization, with reported distinctions between animate, inanimate large, and
inanimate small objects. While there is some evidence for category specific
effects in the medial temporal lobe (MTL), in particular in perirhinal and
parahippocampal cortex, it is currently unclear whether domain level organization
is also present across these structures. To this end, we used fMRI with a
continuous recognition memory task. Stimuli were images of objects from several
different categories, which were either animate or inanimate, or large or small
within the inanimate domain. We employed representational similarity analysis
(RSA) to test the hypothesis that object-evoked responses in MTL structures
during recognition-memory judgments also show evidence for domain-level
organization along both dimensions. Our data support this hypothesis.
Specifically, object representations were shaped by either animacy, real-world
size, or both, in perirhinal and parahippocampal cortex, and the hippocampus.
While sensitivity to these dimensions differed across structures when probed
individually, hinting at interesting links to functional differentiation,
similarities in organization across MTL structures were more prominent overall.
These results argue for continuity in the organization of object representations
in the ventral visual stream and the MTL.
PMID- 29947038
TI - FeP@C Nanotube Arrays Grown on Carbon Fabric as a Low Potential and Freestanding
Anode for High-Performance Li-Ion Batteries.
AB - An anode of self-supported FeP@C nanotube arrays on carbon fabric (CF) is
successfully fabricated via a facile template-based deposition and
phosphorization route: first, well-aligned FeOOH nanotube arrays are simply
obtained via a solution deposition and in situ etching route with hydrothermally
crystallized (Co,Ni)(CO3 )0.5 OH nanowire arrays as the template; subsequently,
these uniform FeOOH nanotube arrays are transformed into robust carbon-coated Fe3
O4 (Fe3 O4 @C) nanotube arrays via glucose adsorption and annealing treatments;
and finally FeP@C nanotube arrays on CF are achieved through the facile
phosphorization of the oxide-based arrays. As an anode for lithium-ion batteries
(LIBs), these FeP@C nanotube arrays exhibit superior rate capability (reversible
capacities of 945, 871, 815, 762, 717, and 657 mA h g-1 at 0.1, 0.2, 0.4, 0.8,
1.3, and 2.2 A g-1 , respectively, corresponding to area specific capacities of
1.73, 1.59, 1.49, 1.39, 1.31, 1.20 mA h cm-2 at 0.18, 0.37, 0.732, 1.46, 2.38,
and 4.03 mA cm-2 , respectively) and a stable long-cycling performance (a high
specific capacity of 718 mA h g-1 after 670 cycles at 0.5 A g-1 , corresponding
to an area capacity of 1.31 mA h cm-2 at 0.92 mA cm-2 ).
PMID- 29947039
TI - 3D printing of fetal heart using 3D ultrasound imaging data.
PMID- 29947040
TI - Nanostructured Thin Films of Moderately Functionalized PMMA-b-PS.
AB - A library of poly(methyl methacrylate)-block-polystyrene (PMMA-b-PS) block
copolymers (BCPs) bearing small amounts (<10 mol%) of functional comonomer in
either one or both blocks is investigated for their phase separation behavior in
bulk and in thin films. Particularly, functionalities typically involved in
modern postpolymerization modifications are considered, e.g., azide,
pentafluorophenyl, furfuryl. Small-angle X-ray scattering and atomic force
microscopy are employed to determine the characteristic dimensional features of
lamellae-forming BCPs, which differ essentially in the functional groups. It is
shown that the presence of the reactive moieties does not perturb the ability to
phase separate in bulk, yet has an impact on the dimensions of the domains. Using
a classic two-step procedure involving surface neutralization with a statistical
PMMA-co-PS copolymer, it is observed that some functional copolymers are not able
to form homogeneous thin films. Solvent stability and crosslinking ability of the
films are then briefly assessed as a first step to establishing the functional
films as nanoresolved molecular immobilization platform with feature sizes of 20
nm and below.
PMID- 29947041
TI - Eight-year trends in the Australian surgical approach to pterygium removal.
AB - IMPORTANCE: Pterygium is a very common disease in Australia but the statistical
data on the provision of pterygium surgical services is poorly understood.
BACKGROUND: This study evaluated the trends in the types of surgeries performed
for pterygium in Australia over an eight period. DESIGN: Retrospective cross
sectional study. PARTICIPANTS: All surgeries performed for pterygium in Australia
from 2005 to 2010 in the Medicare system. METHODS: Eight years of Medicare data
were analysed for services performed with pterygium removal. MAIN OUTCOME
MEASURES: Concurrently used MBS item numbers 42 686 (pterygium removal) with 42
641 (conjunctival autograft) and also 42 686 with any other ophthalmic item
number. RESULTS: Pterygium removal was undertaken together with conjunctival
autografting in 73% of patients in 2005 rising to 88% in 2010. Five other non
related surgical procedures were performed simultaneously with pterygium removal
in 10% of patients in 2005 decreasing to 5.9% in 2012. CONCLUSIONS AND RELEVANCE:
About 12% of pterygium surgeries are not combined with a conjunctival autograft.
It is possible that these may have been used with an adjuvant such as mitomycin
or radiotherapy, or performed as simple excision. Allowing for the possibility
that billing errors may have occurred it is still likely that in 5.9% of
patients, other procedures that would normally not be performed with pterygium
surgery, are undertaken simultaneously and may have an adverse outcome on the
inappropriate concurrent surgery and on the recurrence rate of the pterygium. The
surgeon should carefully review billing codes before submitting them to Medicare.
PMID- 29947042
TI - Laser-Enabled Processing of Stretchable Electronics on a Hydrolytically
Degradable Hydrogel.
AB - Degradable electronics represent a rapidly emerging field of science and
technology with the potential to serve short-term medical implantation
applications where the device disappears once its function is complete. Despite
many efforts in developing new types of degradable electronics, many of such
systems are nonelastic and incompatible with the dynamic motion of native
soft/elastic biological tissues. Herein, a photo-crosslinkable hydrogel with
integrated electronics that are highly stretchable and degradable in liquid
environments is demonstrated. The fabrication process takes advantage of facile
laser micromachining of conductive patterns directly onto the hydrogel under
ambient conditions and permanent hydrogel-hydrogel bonding. The robustness and
degradation rate of hydrogel and the laser-processed encapsulated stretchable
circuits is systematically investigated in different solutions under various
conditions. Biocompatibility tests with non-neoplastic cells (HMT 3522 S1) and
cancer cells (T4-2 and MDA-MB-231) are performed in 2D and 3D cell culture
systems to confirm instead of evaluate the safety of the hydrogel and its
byproducts during degradation as well as the zinc metal used in this technology.
As a proof of concept, a stretchable hydrogel-based device that can be used for
remote/wireless delivery of thermal energy into the tissue in contact with the
hydrogel is fabricated.
PMID- 29947043
TI - Association between sugammadex and anaphylaxis in pediatric patients: A nested
case-control study using a national inpatient database.
AB - BACKGROUND: Sugammadex is used as a reversal drug during anesthesia. Although
several case reports have described anaphylaxis following sugammadex infusion,
little is known about the relationship between sugammadex and anaphylaxis,
particularly in pediatric patients. AIMS: The aim of this retrospective study was
to investigate the association between sugammadex and in-hospital anaphylaxis in
pediatric patients who underwent general anesthesia. METHODS: We identified
patients who underwent general anesthesia in a Japanese national inpatient
database between July 2010 and March 2016. We conducted 1-4 case-control matching
between patients with and without perioperative anaphylaxis. We calculated the
adjusted odds ratio for sugammadex use and occurrence of anaphylaxis, using a
conditional logistic regression analysis with adjustment for duration of
anesthesia, antibiotics, and blood transfusions. RESULTS: Among 835 405 patients
who underwent general anesthesia, we identified 149 (0.018%) patients with
anaphylactic shock and 472 (0.056%) with a combination of anaphylaxis associated
signs/symptoms and skin lesions. Sugammadex use was not significantly associated
with anaphylactic shock (odds ratio, 0.80; 95% confidence interval, 0.53-1.21; P
= .29) or the combination of anaphylaxis associated signs/symptoms and skin
lesions (odds ratio, 1.25; 95% confidence interval, 0.97-1.60; P = .08).
CONCLUSION: The present study showed no significant association between
sugammadex and perioperative anaphylaxis in pediatric patients who underwent
general anesthesia.
PMID- 29947044
TI - High Irisin levels in nondiabetic HIV-infected males are associated with insulin
resistance, nonalcoholic fatty liver disease, and subclinical atherosclerosis.
AB - OBJECTIVE: HIV infection is associated with an increased risk of cardiovascular
disease. Irisin is a miokyne secreted by skeletal muscle, which may influence
insulin homeostasis, nonalcoholic fatty liver disease (NAFLD) and
atherosclerosis. Our objective was to evaluate the relationships between serum
irisin, insulin homeostasis, NAFLD and subclinical atherosclerosis in HIV
infected males. DESIGN: Cross-sectional study in a cohort of HIV-infected
patients. PATIENTS: Inclusion criteria: men older than 18 years; antiretroviral
therapy (ART) -naive or on effective ART (<50 HIV-1 RNA copies/mL) without
changes in the previous 6 months; no diabetes or hepatitis C. MEASUREMENTS:
Irisin was measured by enzymatic immunoassay (Phoenix Pharmaceuticals), insulin
sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR), as
well as the 2-hour continuous infusion of glucose with model assessment (CIGMA
HOMA). Hepatic steatosis was measured by 1-H magnetic resonance spectroscopy,
subclinical atherosclerosis by evaluation of carotid intima-media thickness (C
IMT), measured by Ultrasonography. RESULTS: Eight nine men (age 42.0 +/- 8.3
years, duration of HIV infection 7.9 +/- 5.6 years, CD4 count 547 +/- 279
cells/mL) were included. Circulating irisin was positively related to HOMA-IR and
CIGMA-HOMA, hepatic triglyceride content, and to VAT/SAT ratio. Higher irisin
concentrations were associated with higher C-IMT, although this association did
not persist in multivariate analysis. Lipodystrophy and a higher baseline PAI-1
concentration were independently associated with C-IMT. CONCLUSIONS: In male HIV
patients without diabetes, higher irisin concentrations are positively associated
with insulin resistance, NAFLD and subclinical atherosclerosis. However, waist
hip-ratio is the main determinant of insulin resistance, and PAI-1 and
lipodystrophy were the strongest determinants of IMT in this population.
PMID- 29947045
TI - Assessing the impact of the new ICD-10-CM coding system on pharmacoepidemiologic
studies-An application to the known association between angiotensin-converting
enzyme inhibitors and angioedema.
AB - PURPOSE: To replicate the well-established association between angiotensin
converting enzyme inhibitors versus beta blockers and angioedema in the
International Classification of Diseases, 10th Revision, Clinical Modification
(ICD-10-CM) era. METHODS: We conducted a retrospective, inception cohort study in
a large insurance database formatted to the Sentinel Common Data Model. We
defined study periods spanning the ICD-9-CM era only, ICD-10-CM era only, and ICD
9-CM and ICD-10-CM era and conducted simple-forward mapping (SFM), simple
backward mapping (SBM), and forward-backward mapping (FBM) referencing the
General Equivalence Mappings to translate the outcome (angioedema) and covariates
from ICD-9-CM to ICD-10-CM. We performed propensity score (PS)-matched and PS
stratified Cox proportional hazards regression to estimate hazard ratios (HRs)
and 95% confidence intervals (CIs). RESULTS: In the ICD-9-CM and ICD-10-CM eras
spanning April 1 to September 30 of 2015 and 2016, there were 152 017 and 145 232
angiotensin-converting enzyme inhibitor initiators and 115 073 and 116 652 beta
blocker initiators, respectively. The PS-matched HR was 4.19 (95% CI, 2.82-6.23)
in the ICD-9-CM era, 4.37 (2.92-6.52) in the ICD-10-CM era using SFM, and 4.64
(3.05-7.07) in the ICD-10-CM era using SBM and FBM. The PS-matched HRs from the
mixed ICD-9-CM and ICD-10-CM eras ranged from 3.91 (2.69-5.68) to 4.35 (3.33
5.70). CONCLUSION: The adjusted HRs across different diagnostic coding eras and
the use of SFM versus SBM and FBM produced numerically different but clinically
similar results. Additional investigations as ICD-10-CM data accumulate are
warranted.
PMID- 29947046
TI - Low-Coordinated Edge Sites on Ultrathin Palladium Nanosheets Boost Carbon Dioxide
Electroreduction Performance.
AB - Electrochemical conversion of carbon dioxide (CO2 ) to value-added products is a
possible way to decrease the problems resulting from CO2 emission. Thanks to the
eminent conductivity and proper adsorption to intermediates, Pd has become a
promising candidate for CO2 electroreduction (CO2 ER). However, Pd-based
nanocatalysts generally need a large overpotential. Herein we describe that
ultrathin Pd nanosheets effectively reduce the onset potential for CO by exposing
abundant atoms with comparatively low generalized coordination number. Hexagonal
Pd nanosheets with 5 atomic thickness and 5.1 nm edge length reached CO faradaic
efficiency of 94 % at -0.5 V, without any decay after a stability test of 8 h. It
appears to be the most efficient among all of Pd-based catalysts toward CO2 ER.
Uniform hexagonal morphology made it reasonable to build models and take DFT
calculations. The enhanced activity originates from mainly edge sites on
palladium nanosheets.
PMID- 29947047
TI - CXCL13 produced by macrophages due to Fli1 deficiency may contribute to the
development of tissue fibrosis, vasculopathy and immune activation in systemic
sclerosis.
AB - CXCL13, a chemokine for B cells, follicular T cells, T helper 17 cells, and
regulatory T cells, is reported to contribute to the development of systemic
sclerosis (SSc), reflecting aberrant activation of immune system. To better
understand the role of CXCL13 in SSc, we investigated the influence of Fli1
deficiency, a potential predisposing factor of this disease, on CXCL13 expression
and assessed the clinical correlation of serum CXCL13 levels by multivariate
regression analysis. Haploinsufficient loss of Fli1 remarkably induced CXCL13
expression in murine peritoneal macrophages, while gene silencing of FLI1 did not
affect the expression of CXCL13 in human dermal fibroblasts and human dermal
microvascular endothelial cells. Serum CXCL13 levels were elevated in SSc
patients compared with healthy controls and correlated positively with skin score
and negatively with pulmonary function test results. SSc patients with elevated
serum CXCL13 levels had longer disease duration, diffuse cutaneous involvement,
interstitial lung disease (ILD), heart involvement, pulmonary arterial
hypertension, Raynaud's phenomenon, pitting scars, digital ulcers,
telangiectasia, and high serum IgG levels more frequently than the other
patients. In particular, serum CXCL13 levels were associated with ILD and digital
ulcers by multivariate regression analysis. Taken together, these results
indicate that CXCL13 expression is upregulated by Fli1 deficiency in macrophages,
potentially contributing to the development of tissue fibrosis, vasculopathy and
immune activation in SSc, especially ILD and digital ulcers.
PMID- 29947048
TI - Defect Engineering Metal-Free Polymeric Carbon Nitride Electrocatalyst for
Effective Nitrogen Fixation under Ambient Conditions.
AB - Electrocatalytic nitrogen reduction reaction (NRR) under ambient conditions
provides an intriguing picture for the conversion of N2 into NH3 . However,
electrocatalytic NRR mainly relies on metal-based catalysts, and it remains a
grand challenge in enabling effective N2 activation on metal-free catalysts. Here
we report a defect engineering strategy to realize effective NRR performance (NH3
yield: 8.09 MUg h-1 mg-1cat. , Faradaic efficiency: 11.59 %) on metal-free
polymeric carbon nitride (PCN) catalyst. Illustrated by density functional theory
calculations, dinitrogen molecule can be chemisorbed on as-engineered nitrogen
vacancies of PCN through constructing a dinuclear end-on bound structure for
spatial electron transfer. Furthermore, the N-N bond length of adsorbed N2
increases dramatically, which corresponds to "strong activation" system to reduce
N2 into NH3 . This work also highlights the significance of defect engineering
for improving electrocatalysts with weak N2 adsorption and activation ability.
PMID- 29947049
TI - Copper(II) and Sodium(I) Complexes based on 3,7-Diacetyl-1,3,7-triaza-5
phosphabicyclo[3.3.1]nonane-5-oxide: Synthesis, Characterization, and Catalytic
Activity.
AB - The reaction of 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA)
with metal salts of CuII or NaI /NiII under mild conditions led to the oxidized
phosphane derivative 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5
oxide (DAPTA=O) and to the first examples of metal complexes based on the DAPTA=O
ligand, that is, [CuII (MU-CH3 COO)2 (kappaO-DAPTA=O)]2 (1) and
[Na(1kappaOO';2kappaO-DAPTA=O)(MeOH)]2 (BPh4 )2 (2). The catalytic activity of 1
was tested in the Henry reaction and for the aerobic 2,2,6,6-tetramethylpiperidin
1-oxyl (TEMPO)-mediated oxidation of benzyl alcohol. Compound 1 was also
evaluated as a model system for the catechol oxidase enzyme by using 3,5-di-tert
butylcatechol as the substrate. The kinetic data fitted the Michaelis-Menten
equation and enabled the obtainment of a rate constant for the catalytic
reaction; this rate constant is among the highest obtained for this substrate
with the use of dinuclear CuII complexes. DFT calculations discarded a bridging
mode binding type of the substrate and suggested a mixed-valence CuII /CuI
complex intermediate, in which the spin electron density is mostly concentrated
at one of the Cu atoms and at the organic ligand.
PMID- 29947050
TI - Fetal exome sequencing: yield and limitations in a single tertiary center.
AB - OBJECTIVE: To explore the indications and diagnostic outcomes of fetal exomes in
a single referral center. METHODS: 77 unrelated fetal samples underwent exome
sequencing between 2012-2017. Indications, turnaround time, diagnostic rates, and
pregnancy outcomes were investigated. RESULTS: The most common indication for
fetal exome sequencing was multiple malformations (21/77, 27%), followed by
isolated brain malformations (15/77, 19%). Twelve fetuses (15%) were referred for
isolated increased nuchal translucency (IINT). Exome analysis was diagnostic for
16 fetuses (21%); when sub-classified to fetal malformations vs. IINT it became
clear that exome analysis did not reveal any known or probable pathogenic
variants in IINT whereas among the remaining fetuses, a molecular diagnosis was
reached in 16/65 (25%). Proband-only cases received a diagnosis more often than
trio exomes. CONCLUSION: Exome sequencing has the potential to provide molecular
diagnoses in cases where conventional prenatal cytogenetic testing is negative. A
referral bias of consanguineous cases could account for the high diagnostic rate
for proband-only sequencing. Syndrome-specific prognostic information enables
parents to make informed decisions, whereas challenges include time limitations
and variant interpretation in the setting of non-specific fetal findings. As we
report only established disease-gene associations, further segregation and
functional studies in a research setting are expected to significantly increase
the diagnostic yield. This article is protected by copyright. All rights
reserved.
PMID- 29947052
TI - Consanguinity increases the risk for aggressive periodontitis.
AB - BACKGROUND AND OBJECTIVE: Genetic predisposition is an important factor for
developing aggressive periodontitis (AgP); however, previous studies only focused
on individual families where consanguineous marriages have not been considered.
Thus, there is a debate in the understanding of the genetic features of this
disease. The present study aims to compare the genetic features of AgP in
individuals with and without history of consanguineous marriages. MATERIAL AND
METHODS: Thirty-three probands from 16 pedigrees with history of consanguineous
marriage and 17 pedigrees without history of consanguineous marriage were
analyzed in terms of heritability of AgP. Detailed clinical evaluations of the
probands showing their periodontal health and their family medical histories were
obtained. The gingival index, plaque index, bleeding on probing, suppuration,
probing pocket depth and clinical attachment level data were analyzed and
compared between groups. The gender differences were also taken into account to
determine the mode of inheritance of AgP. RESULTS: The gingival index, bleeding
on probing, suppuration, probing pocket depth and clinical attachment level
scores were significantly different between the affected and unaffected groups
for both genders, which were consistent with the diagnosis of AgP. Strikingly,
when the consanguineous group and the non-consanguineous group were compared, the
siblings of the consanguineous group displayed approximately 8 times more
prevalence of AgP (15.15%) compared to the siblings of the probands in the non
consanguineous group (1.89%) (P = .022). In addition, the mode of transmission of
the disease was found to fit better to the autosomal recessive inheritance
pattern. CONCLUSION: Current findings indicate that AgP is segregated on
autosomal chromosomes and consanguineous marriage increases the likelihood of
developing this disease.
PMID- 29947051
TI - Re-inventing the randomized controlled trial in medical oncology: The registry
based trial.
AB - Substantial progress has recently been made in optimizing the management of
cancer patients, resulting in major gains in survival and quality of life. Much
of this progress has resulted from the serial testing of promising treatment
strategies, typically using prospective randomized controlled trials to compare
outcomes achieved with the new approach versus the current standard(s) of care.
However, there is an ever-expanding list of important questions that are
difficult to investigate, particularly with respect to determining the optimal
sequencing and combination of proven active agents. With the rapidly growing list
of clinical, pathologic and molecular characteristics that promise to predict
treatment benefit and/or risk for defined patient subsets, many new questions
regarding how best to personalize our approach to treatment selection are
emerging. These questions can be investigated in the context of registry-based
randomized clinical trials. Recently, the potential of registry-based randomized
clinical trials was demonstrated in cardiology, highlighting the ability to
rapidly recruit large numbers of patients to a trial addressing an important
clinical question, with minimal cost and high external validity. In this review,
we discuss the challenges and limitations of conventional clinical trials in
multidisciplinary cancer care, describe the potential advantages of registry
based randomized trials, and highlight several registry-based oncology studies
that are already underway to demonstrate the feasibility of this approach.
PMID- 29947054
TI - Unilateral petrified ear.
PMID- 29947053
TI - Prediction of enteric methane emission from beef cattle in Southeast Asia.
AB - We conducted a meta-data analysis to develop prediction equations to estimate
enteric methane (CH4 ) emission from beef cattle in Southeast Asia. The dataset
was obtained from 25 studies, which included 332 individual observations on
nutrient intakes, digestibilities, and CH4 emissions. Cattle were provided
tropical forage or rice straw, with or without concentrates in individual pens
equipped with indirect open-circuit head hood apparatus. The simplest and best
equation to predict daily CH4 emission was CH4 (g/day) = 22.71 (+/-1.008) * dry
matter intake (DMI, kg/day) + 8.91 (+/-10.896) [R2 = 0.77; root mean square
error (RMSE) = 19.363 g/day]. The best equation to predict CH4 energy as a
proportion of gross energy intake (CH4 -E/GEI, J/100 J) was obtained using DMI
per body weight (DMIBW, kg/100 kg), content (g/100 g DM) of ether extract (EE)
and crude protein (CP), and DM digestibility (DMD, g/100 g); CH4 -E/GEI = -0.782
(+/-0.2526) DMIBW - 0.436 (+/-0.0548) EE - 0.073 (+/-0.0218) CP + 0.049 (+/
0.0097) DMD + 8.654 (+/-0.6517) (R2 = 0.39; RMSE = 1.3479 J/100 J GEI). It was
indicated that CH4 emissions from beef cattle in Southeast Asia are predictable
using present developed models including simple indices.
PMID- 29947055
TI - Socioeconomic influences on brain function: implications for health.
AB - Socioeconomic-based disparities in physical health outcomes are well established,
with individuals from lower socioeconomic status (SES) backgrounds being more
likely to experience chronic disease morbidity and early mortality compared to
those from higher SES strata. While numerous studies in recent decades have
focused on understanding the contextual, psychosocial, and biological mechanisms
linking SES and health, the neural pathways that contribute to this relationship
are currently underinvestigated. The present paper reviews and synthesizes the
small number of published studies that have explored links between SES and health
relevant neural functioning. Specifically, current knowledge of the relationship
between socioeconomic factors and neural systems that may be affected by low SES
contexts, including those related to processing threat and stress, responding to
reward, and engaging in emotion regulation, is reviewed. Gaps in our knowledge
that could be filled by health neuroscience research are emphasized, in an effort
to catalyze future studies in this area. Understanding the neural mechanisms
linking SES and health is crucial for building comprehensive models of the
pathways by which social inequalities become health inequalities and may help
identify novel targets for intervention to prevent health disparities. Health
neuroscience research has a critical role to play in this important area of
research.
PMID- 29947056
TI - Left ventricular diastolic function is enhanced after peak exercise in endurance
trained adolescents as well as in their non-trained controls.
AB - The aims of the study were to explore the temporal change of cardiac function
after peak exercise in adolescents, and to investigate how these functional
changes relate to maximal oxygen uptake (VO2max ). The cohort consisted of 27
endurance-trained adolescents aged 13-19 years, and 27 controls individually
matched by age and gender. Standard echocardiography and colour tissue Doppler
were performed at rest, and immediately after as well as 15 min after a maximal
cardio pulmonary exercise test (CPET) on a treadmill. The changes in systolic and
diastolic parameters after exercise compared to baseline were similar in both
groups. The septal E/e'-ratio increased immediately after exercise in both the
active and the control groups (from 9.2 to 11.0; P<0.001, and from 8.7 to 10.2; P
= 0.008, respectively). In a comparison between the two groups after CPET, the
septal E/e'-ratio was higher in the active group both immediately after exercise
and 15 min later compared to the control group (P = 0.007 and P = 0.006,
respectively). We demonstrated a positive correlation between VO2max and cardiac
function including LVEF and E/e' immediately after CPET, but the strongest
correlation was found between VO2max and LVEDV (r = 0.67, P<0.001) as well as
septal E/e' (r = 0.34, P = 0.013). Enhanced diastolic function was found in both
groups, but this was more pronounced in active adolescents. The cardiac
functional response to exercise, in terms of LVEF and E/e', correlates with the
increase in VO2 uptake. These findings in trained as well as un-trained teenagers
have practical implications when assessing cardiac function.
PMID- 29947057
TI - Skin regeneration of amphibians: A novel model for skin regeneration as adults.
AB - Adult mammals do not regenerate the dermis of the skin but form a scar after a
deep skin injury. Since a scar causes serious medical problems, skin
regeneration, instead of formation of a scar, has been strongly desired from a
clinical point of view. Recent studies have suggested multiple origins of
myofibroblasts, which are scar-forming cells in skin wound healing of mammals.
While amphibians have skin structures that are basically common to mammals as
tetrapods, both urodele and anuran amphibians regenerate almost complete skin
structures including the dermis and secretion glands without forming a remarkable
scar after a deep skin injury. In skin regeneration of a metamorphosed Xenopus
laevis, an amphibian, cells that resemble limb blastema cells accumulate under
the epidermis after injury and cells from subcutaneous tissues (tissues
underlying the skin) contribute to skin regeneration. The skin of urodele
amphibians and that of anuran amphibians provide valuable models for studying
skin regeneration as adults. Recent progress in transgenesis and genome editing
techniques with whole genome sequencing in Xenopus and an axolotl have enabled
comparative analyses by molecular genetics of mammal skin and amphibian skin.
Such comparative analyses would enable direct comparison of scar-forming
myofibroblasts in mammals and blastema-like cells that contribute to skin
regeneration in amphibians, ultimately leading to realization of skin
regeneration in adult mammals. Amphibian skin regeneration will also be useful
for determining how to step up skin regeneration to a higher level of
regeneration such as limb regeneration in the future.
PMID- 29947059
TI - Factors affecting the health-related quality of life in community-dwelling
elderly people.
AB - OBJECTIVE: The purpose of this study was to investigate the determinants of the
health-related quality of life of elderly people in Korea by applying the
Andersen model. DESIGN AND SAMPLE: This study was a descriptive survey.
Participants were 240 elderly people over 65 years of age living in a community.
MEASURES: A hierarchical multiple regression was performed to analyze the factors
related to the health-related quality of life, including predisposing, enabling,
and need factors, and health behaviors. RESULTS: Need factors, that is, self
reported health status, were the most significant in influencing the health
related quality of life of the elderly people; predisposing factors were age and
education level, and enabling factors were income and activities of daily living.
CONCLUSION: The findings of this study can be used to develop a community-based
intervention program and to establish a policy for improving the quality of life
of elderly people.
PMID- 29947058
TI - Behavioral interventions in health neuroscience.
AB - Many chronic health concerns (obesity, addiction, stress, chronic pain, and
depression) have garnered recent attention for their increasing frequency,
intractability, and serious health consequences. Because they are often difficult
to treat and there are not always effective pharmacological treatments, many
patients are pursuing behavioral interventions for these conditions. Experimental
behavioral intervention studies have shown some efficacy for health, but the
mechanisms for these treatments are not well understood. Health neuroscience is a
burgeoning field that seeks to link neural function and structure with physical
and mental health. Through this lens, initial studies have begun to investigate
how behavioral interventions modulate neural function in ways that lead to
improvements in health markers and outcomes. Here, we provide a review of these
studies in terms of how they modulate key neurobiological systems, and how
modulation of these systems relates to physical health and disease outcomes. We
conclude with discussion of opportunities for future research in this promising
area of study.
PMID- 29947060
TI - Efficacy and safety of insulin glargine 300 U/mL vs insulin degludec in patients
with type 2 diabetes: A randomized, open-label, cross-over study using continuous
glucose monitoring profiles.
AB - AIMS/INTRODUCTION: Compared with glargine 100 U/mL (Gla100), glargine 300 U/mL
(Gla300) and degludec (Deg) - the ultralong-acting insulins - reportedly have
more stable effects and reduce the risk of hypoglycemia. Currently, they are
considered to be the most useful basal insulins. The present study aimed to
compare the efficacy and safety of Gla300 and Deg on glycemic control using
continuous glucose monitoring. MATERIALS AND METHODS: In this single-center, open
label, parallel-group, two-period, cross-over study, 30 patients with type 2
diabetes were randomized to once-daily Gla300 followed by Deg with the same units
(n = 15) or vice versa (n = 15). The primary end-points of this study were the
mean percentage of time within the target glucose range of 70-180 mg/dL as
efficacy and hypoglycemia of <70 mg/dL as safety indicators, as measured using
continuous glucose monitoring during each treatment period. RESULTS: The mean
percentage of time within the target glucose range was not different between
Gla300 and Deg (77.8 +/- 19.2 vs 76.9 +/- 18.3%, P = 0.848). However, the mean
percentage of time of hypoglycemia with Gla300 was significantly lower than that
of Deg (1.3 +/- 2.7 vs 5.5 +/- 6.4%, P = 0.002). In the secondary safety end
points, the mean percentage of time of severe hypoglycemia (<54 mg/dL) or
nocturnal hypoglycemia with Gla300 was also significantly lower than that of Deg.
CONCLUSIONS: The present study showed the comparable efficacy of Gla300 and Deg
on glycemic control; however, the risk of hypoglycemia was markedly lower for
Gla300 than for Deg.
PMID- 29947061
TI - Peptide Bond Formations through Flow Chemistry.
PMID- 29947062
TI - Simultaneous reconstruction of the thumb defect and coverage of the failed first
dorsal metacarpal artery flap donor site by using the anterolateral thigh flap
and its vascular pedicle tissue.
PMID- 29947063
TI - In Situ Crosslinking of Nanoparticles in Polymerization-Induced Self-Assembly via
ARGET ATRP of Glycidyl Methacrylate.
AB - Polymerization-induced self-assembly (PISA) and in situ crosslinking of the
formed nanoparticles are successfully realized by activators regenerated by
electron-transfer atom transfer radical polymerization (ARGET ATRP) of glycidyl
methacrylate (GMA) or a mixture of GMA/benzyl methacrylate (BnMA) monomers in
ethanol. Poly(oligo(ethylene oxide) methyl ether methacrylate) was employed as
macroinitiator/stabilizer, and a cupric bromide/tris(pyridin-2-ylmethyl)amine
complex as catalyst. Tin (2-ethylhexanoate) was used as reducing agent for ARGET
ATRP, and simultaneously acted as a catalyst for ring-opening polymerization of
oxirane ring in GMA. The kinetics shows that the double bond in GMA was
completely polymerized in 4.0 h, while only a 33% conversion of oxirane ring in
GMA was reached at 117.0 h. Such a large difference would guarantee a smooth PISA
and a subsequent in situ crosslinking of formed nanoparticles. The transmission
electron microscopy and dynamic light scattering show spherical nanoparticles
formed. With a feed molar ratio [BnMA]0 /[GMA]0 = 150/50, 100/100, and 50/150,
the nanoparticles formed in ethanol can dissociate or swell in toluene. When pure
GMA was used, the solid nanoparticles were observed in toluene or ethanol. The
ARGET ATRP provides an efficient strategy to stabilize the nanoparticles formed
in the PISA of GMA-containing system.
PMID- 29947064
TI - Homojunction of Oxygen and Titanium Vacancies and its Interfacial n-p Effect.
AB - The homojunction of oxygen/metal vacancies and its interfacial n-p effect on the
physiochemical properties are rarely reported. Interfacial n-p homojunctions of
TiO2 are fabricated by directly decorating interfacial p-type titanium-defected
TiO2 around n-type oxygen-defected TiO2 nanocrystals in amorphous-anatase
homogeneous nanostructures. Experimental measurements and theoretical
calculations on the cell lattice parameters show that the homojunction of oxygen
and titanium vacancies changes the charge density of TiO2 ; a strong EPR signal
caused by oxygen vacancies and an unreported strong titanium vacancies signal of
2D 1 H TQ-SQ MAS NMR are present. Amorphous-anatase TiO2 shows significant
performance regarding the photogeneration current, photocatalysis, and energy
storage, owing to interfacial n-type to p-type conductivity with high charge
mobility and less structural confinement of amorphous clusters. A new
"homojunction of oxygen and titanium vacancies" concept, characteristics, and
mechanism are proposed at an atomic-/nanoscale to clarify the generation of
oxygen vacancies and titanium vacancies as well as the interface electron
transfer.
PMID- 29947065
TI - Exceptionally Ductile and Tough Biomimetic Artificial Nacre with Gas Barrier
Function.
AB - Synthetic mimics of natural high-performance structural materials have shown
great and partly unforeseen opportunities for the design of multifunctional
materials. For nacre-mimetic nanocomposites, it has remained extraordinarily
challenging to make ductile materials with high stretchability at high fractions
of reinforcements, which is however of crucial importance for flexible barrier
materials. Here, highly ductile and tough nacre-mimetic nanocomposites are
presented, by implementing weak, but many hydrogen bonds in a ternary nacre
mimetic system consisting of two polymers (poly(vinyl amine) and poly(vinyl
alcohol)) and natural nanoclay (montmorillonite) to provide efficient energy
dissipation and slippage at high nanoclay content (50 wt%). Tailored interactions
enable exceptional combinations of ductility (close to 50% strain) and toughness
(up to 27.5 MJ m-3 ). Extensive stress whitening, a clear sign of high internal
dynamics at high internal cohesion, can be observed during mechanical
deformation, and the materials can be folded like paper into origami planes
without fracture. Overall, the new levels of ductility and toughness are
unprecedented in highly reinforced bioinspired nanocomposites and are of critical
importance to future applications, e.g., as barrier materials needed for
encapsulation and as a printing substrate for flexible organic electronics.
PMID- 29947066
TI - Racial disparities in the choice of definitive treatment for squamous cell
carcinoma of the oral cavity.
AB - BACKGROUND: Definitive surgery is recommended for oral cavity squamous cell
carcinoma (SCC). The purpose of this study was to present our assessment of the
disparities in treatment selection for oral cavity SCC. METHODS: Non-Hispanic
white and non-Hispanic black patients with oral cavity SCC were identified in the
National Cancer Database (NCDB). Regression models were used to estimate relative
risk (RR) of receiving surgery and absolute difference between non-Hispanic white
and non-Hispanic black patients. RESULTS: There were 82.3% of non-Hispanic white
patients who received surgery, compared to 64.2% of non-Hispanic black patients
(P < .001). The non-Hispanic black patients were less likely to receive surgery
than non-Hispanic white patients (RR 0.87) with an absolute difference of 10.9%.
The non-Hispanic black patients were significantly more likely to not be offered
surgery (RR 1.42) and to refuse recommended surgery (RR 1.38) but not have a
contraindication to surgery (RR 1.17). CONCLUSION: The non-Hispanic black
patients are less likely to receive or be recommended surgery for oral cavity SCC
and are more likely to refuse surgery. Further study is needed to identify
strategies to close this disparity.
PMID- 29947067
TI - Structural changes in the puborectalis muscle after vaginal delivery.
PMID- 29947068
TI - Compartmentalized endoscopic resection of the olfactory cleft for nasal
intestinal adenocarcinomas.
AB - BACKGROUND: The purpose of this study was to describe the pathology of the
different compartments in endoscopic resection of nasal intestinal-type
adenocarcinomas (ITACs) and its relationships with oncologic outcomes. METHODS:
This retrospective study included all patients endoscopically operated for nasal
ITACs, followed by radiotherapy in the majority of cases, between 2004 and 2014.
The surgery systematically separated 3 compartments: ethmoid lateral mass,
olfactory cleft, and anterior cranial fossa (in cases with skull-base invasion)
to analyze their pathological "focal" or "massive" invasion by the tumor.
RESULTS: Sixty-seven patients (aged 69.2 +/- 9.8 years) were included. Twenty
nine patients (43.3%) had only pathological focal invasion. At 61.0 +/- 41.7
months of mean follow-up, the recurrence rates were 34.2% in the group with
massive invasion and 10.3% in the group with focal invasion (P = .023). The
disease-specific death rate had a tendency to be higher in the group with massive
invasion (23.7% vs 6.9% for the group with focal invasion; P = .097). By Kaplan
Meier analysis, the 5-year disease-specific survival rate was better in the group
with focal invasion than the group with massive invasion (P = .01). The 5-year
overall survival was not different between the 2 groups (47.4% and 65.5% for
focal invasion and massive invasion respectively; P = .14). CONCLUSION:
Compartmentalized endoscopic resection, combined with postoperative radiotherapy,
is one way to operate on nasal ITACs with good oncologic outcomes.
PMID- 29947069
TI - Bioinspired Color Materials Combining Structural, Dye, and Background Colors.
AB - Human beings have developed many dyes and pigments and use them for printed and
display materials to share information. Today's information society is not
possible without these color materials. Some living organisms utilize body color
for information exchange and protection by skilfully combining dye, structural,
and background colors to realize a body color change based on circumstances. In
this study, inspired by the extraordinary body color changes of living things, a
composite color material combining photochromic dyes, a black substance, a
spherical colloidal crystal exhibiting a structural color, and a background color
is prepared. In addition to combining a dye color and a structural color that
changes upon light irradiation, the contribution of the different effects of the
background color on each coloring property allows the construction of a color
material that can reversibly change into various colors under different
conditions.
PMID- 29947070
TI - A Stable Quasi-Solid-State Sodium-Sulfur Battery.
AB - Ambient-temperature sodium-sulfur (Na-S) batteries are considered a promising
energy storage system due to their high theoretical energy density and low costs.
However, great challenges remain in achieving a high rechargeable capacity and
long cycle life. Herein we report a stable quasi-solid-state Na-S battery enabled
by a poly(S-pentaerythritol tetraacrylate (PETEA))-based cathode and a (PETEA
tris[2-(acryloyloxy)ethyl] isocyanurate (THEICTA))-based gel polymer electrolyte.
The polymeric sulfur electrode strongly anchors sulfur through chemical binding
and inhibits the shuttle effect. Meanwhile, the in situ formed polymer
electrolyte with high ionic conductivity and enhanced safety successfully
stabilizes the Na anode/electrolyte interface, and simultaneously immobilizes
soluble Na polysulfides. The as-developed quasi-solid-state Na-S cells exhibit a
high reversible capacity of 877 mA h g-1 at 0.1 C and an extended cycling
stability.
PMID- 29947071
TI - Stabilizing Lithium Plating by a Biphasic Surface Layer Formed In Situ.
AB - The dendritic growth of Li metal leads to electrode degradation and safety
concerns, impeding its application in building high energy density batteries.
Forming a protective layer on the Li surface that is electron-insulating, ion
conducting, and maintains an intimate interface is critical. We herein
demonstrate that Li plating is stabilized by a biphasic surface layer composed of
a lithium-indium alloy and a lithium halide, formed in situ by the reaction of an
electrolyte additive with Li metal. This stabilization is attributed to the fast
lithium migration though the alloy bulk and lithium halide surface, which is
enabled by the electric field across the layer that is established owing to the
electron-insulating halide phase. A greatly stabilized Li-electrolyte interface
and dendrite-free plating over 400 hours in Li|Li symmetric cells using an alkyl
carbonate electrolyte is demonstrated. High energy efficiency operation of the
Li4 Ti5 O12 (LTO)|Li cell over 1000 cycles is achieved.
PMID- 29947072
TI - Are medical students trained in cross-cover?
AB - OBJECTIVES: To examine the current state of cross-cover education in
undergraduate medical education and intern perceived readiness to provide cross
cover. METHODS: An electronic survey was distributed to 126 incoming interns in
surgery, internal medicine, family medicine and paediatrics residencies at a
single academic centre. Information regarding prior cross-cover training,
experience, confidence, and responses to a sample cross-cover case were obtained.
RESULTS: The survey response rate was 69.8% (88 of 126), which included both
partial and complete responses. Fifty-seven interns out of 85 (67.1%) had no
formal training and 51 (60.0%) had no experience performing cross-cover. They
reported feeling unprepared to provide cross-cover, with an average score of 1.8
on a 5-point Likert scale (1, not at all confident; 5, extremely confident).
Interns had more confidence in performing cross-cover tasks if they had prior
direct cross-cover experience (p = 0.001), and were the least confident in
performing the initial evaluation and management of urgent issues (Likert score =
1.6). Scores on the sample case were correlated with the amount of prior
experience with patients (p = 0.06). Only 77.7% of interns indicated that they
would notify their senior resident in two urgent scenarios. Those who reported
higher confidence in knowing when to ask for help were more likely to
appropriately notify their senior colleague (p = 0.005). We identified gaps in
cross-cover training and in the preparedness of incoming interns CONCLUSIONS: We
identified gaps in cross-cover training and in the preparedness of incoming
interns. This has important implications for the first day of residency, when
interns are often asked to perform cross-coverage, yet feel unprepared to do so
and express the greatest concern in urgent cross-cover scenarios. Addressing this
curricular gap is crucial in assuring safe cross-cover care.
PMID- 29947073
TI - Recommendation of fiducial marker implantation for better target tracking using
MV imager in prostate radiotherapy.
AB - PURPOSE: The aim of this study was to develop a model that optimizes the fiducial
marker locations in the prostate to increase detectability of the markers in the
projected EPID images during VMAT treatments. METHODS AND MATERIALS: The fiducial
marker tracking capability for each arc was evaluated through a proposed formula.
The output of the formula, a detectability score, was calculated with the in
house developed software written in MATLAB (The Mathworks, Inc., Natick, MA,
USA). Three unique weighting factors were added to penalize the detectability
score. The detectability scores of four different patterns containing 40
combinations of simulated fiducial marker locations were evaluated with 101
previously treated prostate treatment plans (containing 202 individual arcs). The
results were analyzed for each pattern group and each marker separation distance
on the transverse plane. RESULTS: The maximum detectability of the markers
occurred when they were placed between 10 and 15 mm from the center of the
prostate in the transverse plane and 6-13 mm in the superior-inferior direction.
The detectability decreased when the markers were placed beyond 20 mm in both
directions. CONCLUSIONS: The fiducial marker-based detectability score can be
used to predict the real-time tracking capability. Suggestions for optimal
insertion locations were given to improve prostate motion management using MV
imaging.
PMID- 29947074
TI - Rebuttal from Gregory D. Funk and Alexander V. Gourine.
PMID- 29947075
TI - Aberrant activation of type I interferon system may contribute to the
pathogenesis of anti-MDA5 dermatomyositis.
AB - BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA5)
dermatomyositis (DM) is a distinctive subtype of DM that carries a significant
risk of interstitial lung disease (ILD). The mechanisms remain elusive.
OBJECTIVES: To explore the role of type I interferon (IFN) system in the
pathogenesis of anti-MDA5 DM. METHODS: Twenty anti-MDA5 DM patients were studied
and compared with anti-aminoacyl-tRNA synthetase (ARS) DM patients (n=10) and
autoAb negative DM patients (n=20). The levels of inflammatory cytokines, B cell
activating factor (BAFF), and Krebs von den Lungen-6 (KL-6) in blood were tested
by ELISA and multiplex assays. Expressions of transcripts for IFN-associated
sensors and type I IFN inducible genes in PBMCs were detected by real-time PCR
analysis. Expressions of STAT1, ISG15, and MxA proteins in skin lesions were
analyzed by immunohistochemistry technique. RESULTS: Plasma IFN-alpha levels were
found to dominantly increase in anti-MDA5 DM patients. PBMCs from anti-MDA5 DM
patients were shown to have the significant upregulations of TLR3, TLR7, MDA5,
RIG-I genes as well as serial IFN-inducible genes. Skin biopsies from anti-MDA5
DM patients were characterized by the strong expressions of STAT1, ISG15, and MxA
proteins. In the anti-MDA5 DM/ILD patients with high IFN-alpha production, there
was a positive quantitative correlation between IFN-alpha and BAFF (rs =0.6273,
P=0.0440). In addition, the higher levels of BAFF paralleled to the higher
concentrations of KL-6 (rs =0.8636, P=0.0012). CONCLUSIONS: Our data confirm the
aberrant activation of type I IFN system in anti-MDA5 DM. Overproduction of IFN
alpha linked with BAFF may be implicated in the development of ILD. This article
is protected by copyright. All rights reserved.
PMID- 29947076
TI - Neurological prognostication tools in out-of-hospital cardiac arrest patients in
Danish intensive care units from 2005 to 2013.
AB - BACKGROUND: Neurological prognostication is an essential part of post
resuscitation care in out-of-hospital cardiac arrest (OHCA). This study aims to
assess the use of computed tomography (CT) and magnetic resonance imaging (MR) of
the head, electroencephalography (EEG), and somatosensory evoked potentials
(SSEP) in neurological prognostication in resuscitated OHCA patients and factors
associated with their use in Danish tertiary and non-tertiary centers from 2005
to 2013 and associations with outcome. METHODS: We used the Danish Cardiac Arrest
Registry to identify patients >=18 years of age admitted to intensive care units
due to OHCA of presumed cardiac etiology. CT 0-20 days and MR, SSEP, and EEG >=2
20 days post OHCA were considered related to prognostication. Incidence and
factors associated with procedures were assessed by multiple Cox regression with
death as competing risk. RESULTS: Use of CT, MR, EEG, and SSEP increased during
the study period (CT: 51%-67%, HRCT : 1.06, CI: 1.03-1.08, MR: 2%-5%, P = .08,
EEG: 6%-33%, HREEG : 1.25, CI: 1.19-1.30, SSEP: 4%-15%, HRSSEP : 1.23, CI: 1.15
1.32). EEG and SSEP were more used in tertiary centers than non-tertiary (HREEG :
1.86, CI: 1.51-2.29, HRSSEP : 4.44, CI: 2.86-6.89). Use of CT, SSEP, and EEG were
associated with higher 30-day mortality, and MR was associated with lower (HRCT :
1.15, CI: 1.01-1.30, HRMR : 0.53, CI: 0.37-0.77, HRSSEP : 1.90, CI: 1.57-2.32,
HREEG : 1.75, CI: 1.49-2.05). CONCLUSION: Use of neurological prognostication
procedures increased during the study period. EEG and SSEP were more used in
tertiary centers. CT, EEG and SSEP were associated with increased mortality.
PMID- 29947077
TI - Heterogeneity of tumour-infiltrating lymphocytes in breast cancer and its
prognostic significance.
AB - BACKGROUND AND AIMS: Tumour-infiltrating lymphocytes (TILs) in breast cancer (BC)
provide prognostic and predictive information. The aim of this study was to
assess the spatial and temporal heterogeneity of TILs in BC and its relationship
with immune cell subtypes. METHODS AND RESULTS: Immunohistochemically defined
immune cell subtypes, i.e. those expressing T-cell markers (CD3, CD8, and FOXP3),
a B-cell marker (CD20) and a histiocytic marker (CD68), were evaluated in a large
series (n = 1165) of invasive BCs. A subset of full-face haematoxylin and eosin
(H&E)-stained slides were examined for TILs heterogeneity within primary tumours
and the corresponding local recurrent carcinomas to investigate spatial and
temporal TILs heterogeneity. H&E-stained sections from multiple tumour blocks
(three or four blocks per case) representing different tumour areas were
evaluated to assess TILs interslide heterogeneity and intraslide heterogeneity.
Both average stromal TILs (AV-TILs) and hotspot stromal TILs (HS-TILs) were
assessed. AV-TILs showed associations with all immune cell subtypes; however,
CD3+ cells constituted the main component (mean number of CD3+ was 55), whereas
CD20+ cells constituted the smallest component (mean number of CD20 was 13).
There was no significant statistical difference between TILs across tumour blocks
of the same case (P = 0.251 for AV-TILs and P = 0.162 for HS-TILs). Triple
negative breast cancer (TNBC) showed higher TILs percentage than other BC
subtypes (P < 0.001). High AV-TILs, CD3+ cells, CD8+ cells and CD20+ cells were
associated with longer survival in TNBC patients (P < 0.05). High AV-TILs in
recurrent tumours showed a significant association with shorter post-recurrence
survival (P = 0.004). CONCLUSIONS: Despite the heterogeneity of immune cell type
components, average TILs in one full-face H&E-stained section reliably represent
TILs in the whole tumour. TILs were associated with outcome in TNBC patients, as
well as having prognostic significance for recurrent tumours.
PMID- 29947078
TI - Beyond Bitcoin: potential applications of blockchain technology in dermatology.
PMID- 29947079
TI - CrossTalk proposal: a central hypoxia sensor contributes to the excitatory
hypoxic ventilatory response.
PMID- 29947080
TI - Separation and determination of corynoxine and corynoxine B using chiral ionic
liquid and hydroxypropyl-beta-cyclodextrin as additives by field-amplified sample
stacking in capillary electrophoresis.
AB - A sensitive, fast, and effective method, field-amplified sample stacking (FASS)
in capillary electrophoresis, has been established for the separation and
determination of corynoxine and corynoxine B. Hydroxypropyl-beta-CD (HP-beta-CD)
and tetrabutylammonium-L-glutamic acid (TBA-L-Glu) were used as additives in the
separation system. Electrokinetic injection was chosen to introduce sample from
inlet at 10 kV for 50 s after a water plug (0.5 psi, 4 s) was injected to permit
FASS. The running buffer (pH 6.1) was composed of 40 mM sodium dihydrogen
phosphate solution, 130 mM HP-beta-CD, and 10 mM TBA-L-Glu and the separation
voltage was 20 kV. Under the optimum conditions, corynoxine and corynoxine B were
successfully enriched and separated within 12 min and the sensitivity was
improved approximately by 700-900 folds. Calibration curves were in a good linear
relationship within the range of 62.5-5.00 * 103 ng/mL for both corynoxine and
corynoxine B. The limits of detection (S/N = 3) and quantitation (S/N = 10) were
14.9, 45.2 ng/mL for corynoxine and 11.2, 34.5 ng/mL for corynoxine B,
respectively. Finally, this method was successfully applied for the determination
of corynoxine and corynoxine B in the stems with hooks of Uncaria rhynchophylla
and its formulations.
PMID- 29947081
TI - Colour pattern component phenotypic divergence can be predicted by the light
environment.
AB - The sensory drive hypothesis predicts that across different light environments
sexually selected colour patterns will change to increase an animal's visual
communication efficiency within different habitats. This is because individuals
with more efficient signal components are likely to have more successful matings
and hence produce more offspring. However, how colour pattern signals change over
multiple generations under different light environmental conditions has not been
tested experimentally. Here, we manipulated colour pattern signal efficiency by
providing different ambient light environments over multiple generations to
examine whether male colour pattern components change within large replicated
populations of guppies (Poecilia reticulata). We report that colour patches
change within populations over time and are phenotypically different among our
three different light environments. Visual modelling suggests that the majority
of these changes can be understood by considering the chroma, hue and luminance
of each colour patch as seen by female guppies under each light environment.
Taken together, our results support the hypothesis that different environmental
conditions during signal reception can directly or indirectly drive the
phenotypic diversification of visual signals within species.
PMID- 29947082
TI - Enantioselective separation of twelve pairs of enantiomers on polysaccharide
based chiral stationary phases and thermodynamic analysis of separation
mechanism.
AB - The enantioseparation of twelve pairs of structurally related 1-aryl-1-indanone
derivatives was studied in the normal-phase mode using three different
polysaccharide-type chiral stationary phases, namely Chiralpak IB, Chiralpak IC,
and Chiralpak ID. n-Hexane/2-propanol and n-hexane/ethanol were employed as
mobile phases. Among all the investigated chiral columns, Chiralpak IC exhibited
the most universal and the best enantioseparation ability toward all the
racemates, particularly with the mobile phase composed of n-hexane/2-propanol
(90/10, v/v). Then the effects of column temperature on retention and
enantioselectivity were examined in the range of 25-40 degrees C. Satisfactory
enantioseparation was obtained at ambient temperature. The natural logarithm of
retention and separation factors (ln k and ln alpha) versus the reciprocal of
absolute temperature (1/T) (Van't Hoff plots) were found to be linear for all
racemates, indicating that the retention and separation mechanisms were
independent of temperature in the range investigated. Then, the thermodynamic
parameters (DeltaDeltaH degrees , DeltaDeltaS degrees , and DeltaDeltaG degrees )
were calculated from Van't Hoff plots. These values indicated that the solute
transfer from the mobile to stationary phase was enthalpically favorable, and the
process of enantioseparation was mainly enthalpy controlled. At last, the impact
of small changes in molecular structures of the tested 1-indanone derivatives on
enantioseparation was also discussed.
PMID- 29947083
TI - A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the
Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked
Hypophosphatemia: Week 24 Primary Analysis.
AB - In X-linked hypophosphatemia (XLH), inherited loss-of-function mutations in the
PHEX gene cause excess circulating levels of fibroblast growth factor 23 (FGF23),
leading to lifelong renal phosphate wasting and hypophosphatemia. Adults with XLH
present with chronic musculoskeletal pain and stiffness, short stature, lower
limb deformities, fractures, and pseudofractures due to osteomalacia, accelerated
osteoarthritis, dental abscesses, and enthesopathy. Burosumab, a fully human
monoclonal antibody, binds and inhibits FGF23 to correct hypophosphatemia. This
report summarizes results from a double-blind, placebo-controlled, phase 3 trial
of burosumab in symptomatic adults with XLH. Participants with hypophosphatemia
and pain were assigned 1:1 to burosumab 1 mg/kg (n = 68) or placebo (n = 66)
subcutaneously every 4 weeks (Q4W) and were comparable at baseline. Across
midpoints of dosing intervals, 94.1% of burosumab-treated participants attained
mean serum phosphate concentration above the lower limit of normal compared with
7.6% of those receiving placebo (p < 0.001). Burosumab significantly reduced the
Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC)
stiffness subscale compared with placebo (least squares [LS] mean +/- standard
error [SE] difference, -8.1 +/- 3.24; p = 0.012). Reductions in WOMAC physical
function subscale (-4.9 +/- 2.48; p = 0.048) and Brief Pain Inventory worst pain
(-0.5 +/- 0.28; p = 0.092) did not achieve statistical significance after
Hochberg multiplicity adjustment. At week 24, 43.1% (burosumab) and 7.7%
(placebo) of baseline active fractures were fully healed; the odds of healed
fracture in the burosumab group was 16.8-fold greater than that in the placebo
group (p < 0.001). Biochemical markers of bone formation and resorption increased
significantly from baseline with burosumab treatment compared with placebo. The
safety profile of burosumab was similar to placebo. There were no treatment
related serious adverse events or meaningful changes from baseline in serum or
urine calcium, intact parathyroid hormone, or nephrocalcinosis. These data
support the conclusion that burosumab is a novel therapeutic addressing an
important medical need in adults with XLH.(c) 2018 The Authors. Journal of Bone
and Mineral Research Published by Wiley Periodicals, Inc.
PMID- 29947085
TI - Mixed-methods study of reported clinical cases of undesirable events, medical
errors, and near misses in health care.
AB - RATIONALE, AIMS, AND OBJECTIVES: Patient safety is recognized as a key indicator
of quality of medical care. International experience has shown that all efforts
should focus on the delivery of a safer work environment and health care system
as a whole in order to reduce or mitigate medical errors and their impact on
society. The aim of this study is to investigate and classify the most common
incidents regarding patient safety as well as their contributory factors, based
on personal real-life experiences and situations in medical care reported by
health care professionals. METHODS: A mixed-methods study design was used. Sixty
five respondents participated (aged from 23 to 58 y). Reported cases of
undesirable events (UE), medical errors (ME), and near misses (NM) were
collected, processed, and analysed based on our original conceptual framework. A
qualitative content analysis and descriptive statistics were conducted on the
narratives in all 34 reported valid case files. Intercoder reliability was
measured through the kappa statistics (kappa = .69). The overall agreement of
judgments on all codes was excellent (95%). RESULTS: A total of 29 MEs in 34
cases were reported. In 85% of them, an average of 1.83 contributory factors were
identified. The most common contributory factors were "Incompetence," "Neglect,"
"Severe work overload," and "Shortage of staff." DISCUSSION: Important steps to
prevent medical errors are their identification and reporting. CONCLUSION: Health
care professionals appear able to report UEs, MEs, and NMs occurring in medical
care practice. They seem more willing to report and distinguish incidents related
to MEs than to UEs and NMs.
PMID- 29947084
TI - Sericin enhances the developmental competence of heat-stressed bovine embryos.
AB - We investigated the effects of sericin on the developmental competence of bovine
embryos exposed to heat stress (HS). Putative zygotes were cultured with sericin
and subjected to HS (40.5 degrees C for 6 hr) on Day 2 or 7 followed by
continuous culture at 38.5 degrees C until Day 8. Day 2 HS significantly
decreased blastocyst development on Day 8 as well as mitochondrial activity, and
significantly increased the amount of intracellular reactive oxygen species and
terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL)
positive cells, whereas Day 7 HS only significantly decreased mitochondrial
activity and increased the number of TUNEL-positive cells in Day 8 blastocysts.
These detrimental effects were neutralized by sericin supplementation. Next, to
investigate the potential production of blastocysts with high viability in terms
of thermotolerance, embryos were cultured with sericin until Day 7, and then
exposed to HS in the sericin-free medium. TUNEL-positive cell numbers were
significantly lower in blastocysts produced by sericin culture than in control
blastocysts. Transcript abundance for HSPA1A and BAX was significantly decreased
but IFNT2 levels were increased in blastocysts produced by sericin culture. In
conclusion, these findings demonstrate the anti-oxidative and anti-apoptotic
activities of sericin, and the potential use of sericin to produce embryos with
high viability in vitro.
PMID- 29947086
TI - Dynamic Motion of Organic Ligands in Polar Layered Cobalt Phosphonates.
AB - By introducing the polar methoxy group into phenyl- or benzyl-phosphonate
ligands, four cobalt phosphonates with layered structures are obtained, namely,
[Co(4-mopp)(H2 O)] (1), [Co(4-mobp)(H2 O)] (2), [Co(3-mopp)(H2 O)] (3), and [Co(3
mobp)(H2 O)] (4), where 4- or 3-moppH2 is (4- or 3-methoxyphenyl)phosphonic acid
and 4- or 3-mobpH2 is (4- or 3-methoxybenzyl)phosphonic acid. Compounds 1, 2, and
4 crystallize in the polar space groups Pmn21 or Pna21 , whereas compound 3
crystallizes in the centrosymmetric space group P21 /n. The layer topologies in
the four structures are similar and can be viewed as perovskite type, where the
edge-sharing [Co4 O4 ] rhombi are capped by the PO3 C groups. The phenyl and MeO
groups in compounds 1-3 are heavily disordered, whereas that in 4 is ordered.
Structural comparison based on the data at 296 and 123 K reveals distinct dynamic
motion of the organic groups in compounds 1 and 2. The fluctuation of the polar
MeO groups in these two compounds is confirmed by dielectric relaxation
measurements. In contrast, the fluctuation of polar groups in compounds 3 and 4
is not evident. Interestingly, the dehydrated samples of 3 and 4 (i.e., 3-de and
4-de) exhibit one-step and two-step phase transitions associated with the motion
of polar organic groups, as proven by DSC and dielectric measurements. The
magnetic properties of compounds 1-4 are investigated, and strong
antiferromagnetic interactions are found to mediate between the magnetic centers
through MU-O(P) and O-P-O bridges.
PMID- 29947087
TI - Diverging response patterns of terrestrial and aquatic species to
hydromorphological restoration.
AB - Although experiences with ecological restoration continue to accumulate, the
effectiveness of restoration for biota remains debated. We complemented a
traditional taxonomic analysis approach with information on 56 species traits to
uncover the responses of 3 aquatic (fish, macroinvertebrates, macrophytes) and 2
terrestrial (carabid beetles, floodplain vegetation) biotic groups to 43
hydromorphological river restoration projects in Germany. All taxonomic groups
responded positively to restoration, as shown by increased taxonomic richness (10
164%) and trait diversity (habitat, dispersal and mobility, size, form, life
history, and feeding groups) (15-120%). Responses, however, were stronger for
terrestrial than aquatic biota, and, contrary to our expectation, taxonomic
responses were stronger than those of traits. Nevertheless, trait analysis
provided mechanistic insights into the drivers of community change following
restoration. Trait analysis for terrestrial biota indicated restoration success
was likely enhanced by lateral connectivity and reestablishment of dynamic
processes in the floodplain. The weaker response of aquatic biota suggests
recovery was hindered by the persistence of stressors in the aquatic environment,
such as degraded water quality, dispersal constraints, and insufficient
hydromorphological change. Therefore, river restoration requires combined local-
and regional-scale approaches to maximize the response of both aquatic and
terrestrial organisms. Due to the contrasting responses of aquatic and
terrestrial biota, the planning and assessment of river restoration outcomes
should consider effects on both components of riverine landscapes.
PMID- 29947088
TI - Inflammation and fatigue in early, untreated Parkinson's Disease.
AB - OBJECTIVES: Parkinson's disease (PD)-related fatigue is a significant clinical
problem, and the pathological processes that cause fatigue remain unknown. The
aim of the present study was to explore the possible association of peripheral
inflammation markers and fatigue in PD. MATERIALS & METHODS: We included 47 drug
naive, newly diagnosed PD patients with low (<=3.0) or high (>5.5) fatigue levels
as evaluated by the Fatigue Severity Scale (FSS). Strict diagnostic criteria were
applied for inclusion. Patients with possible confounding causes for fatigue were
excluded. Serum concentrations of a panel of inflammatory markers (IL-8, TNF
alpha, MCP1, MIP-1beta, IL-6, IL-6R, p-selectin, E-selectin-1, ICAM, VCAM-1,
CCL5, IL1-Ra, and TNFR1) were measured using ELISA technology in PD patients with
and without fatigue to assess the potential relationships of fatigue in newly
diagnosed, treatment-naive patients. RESULTS: Fatigued PD patients had
significantly higher levels of the IL-1 receptor antagonist (IL1-Ra) (1790 pg/mL
(SD1007) vs 1262 pg/mL (SD379)) and of the adhesion molecule VCAM 1 (1071 ng/mL
(SD276) vs 895 ng/mL (SD229)) than non-fatigued patients. A binary logistic
regression model, including high or low FSS score as the dependent variable and
UPDRS motor score, MADRS, MMSE, ESS, and IL1-Ra/VCAM-1 as independent variables,
showed a significant effect both for IL1-Ra and VCAM-1. CONCLUSIONS: Higher serum
levels of the inflammatory molecules IL1-Ra and VCAM-1 were associated with
higher fatigue levels in patients with newly diagnosed, drug-naive PD. These
findings highlight an altered immune response as a potential contributor to PD
related fatigue, from the earliest clinical stages of the disease.
PMID- 29947089
TI - Dark-Field Sensors based on Organometallic Halide Perovskite Microlasers.
AB - The detection of nanoscale objects is essential for homeland security,
environmental monitoring, and early-stage diagnostics. In the past few years,
optical sensors have mostly been developed with passive devices such as
microcavity and plasmonic nanostructures, which require external laser sources to
operate and significantly increase the costs and bulks of sensing systems. To
date, the potential of their active counterparts in optical sensors has not been
well explored. Herein, a novel and robust mechanism to detect nanoscale objects
with lead halide perovskite microlasers is demonstrated. Nanoparticles can be
simply detected and sized by measuring the intensity of scattered laser light. In
principle, the proposed concept is also applicable to electrically driven
microlasers and it could find applications in portable point-of-care devices.
PMID- 29947090
TI - Transplantation of kidneys from DCD and DBD donors who died after ligature
asphyxiation: The UK experience.
AB - There is uncertainty about whether hypoxic injury accompanying donor death from
ligature asphyxiation influences renal transplant outcomes, particularly for
recipients of kidneys donated after circulatory death (DCD). The UK Registry
analysis was undertaken to determine transplant outcomes in recipients of kidneys
from donors who died following ligature asphyxiation. From 2003 to 2016, 2.7% (n
= 521) of potential organ donors died following ligature asphyxiation (mostly
suicide by hanging). Of these, 409 (78.5%) donated kidneys for transplantation
(46.9% donation after brain death [DBD] and 53.1% DCD donors) resulting in 650
kidney transplants. Compared to other deceased donors, those dying from ligature
asphyxiation were younger, more often male, and had less hypertension. Unadjusted
patient and graft survival were superior for recipients of both DBD and DCD
kidneys from donors dying after ligature asphyxiation, although after adjustment
for donor/recipient variables, transplant outcomes were similar. A case-control
matched analysis confirmed transplant outcomes for those who received kidneys
from donors dying after ligature asphyxiation were similar to controls. Although
caution is required in interpreting these findings because of potential selection
bias, kidneys from donors dying of ligature asphyxiation suffer an additional
warm ischemic insult that does not apparently adversely influence transplant
outcomes, even for kidneys from DCD donors.
PMID- 29947091
TI - Intraoperative ketamine administration to prevent delirium or postoperative
cognitive dysfunction: A systematic review and meta-analysis.
AB - BACKGROUND: Postoperative cognitive complications are associated with substantial
morbidity and mortality. Ketamine has been suggested to have neuroprotective
effects in various settings. This systematic review evaluates the effects of
intraoperative ketamine administration on postoperative delirium and
postoperative cognitive dysfunction (POCD). METHODS: Medline, Embase and Central
were searched to 4 March 2018 without date or language restrictions. We
considered randomised controlled trials (RCTs) comparing intraoperative ketamine
administration versus no intervention in adults undergoing surgery under general
anaesthesia. Primary outcomes were postoperative delirium and POCD. Non-cognitive
adverse events, mortality and length of stay were considered as secondary
outcomes. Data were independently extracted. The quality of the evidence (GRADE
approach) was assessed following recommendations from the Cochrane collaboration.
Risk ratios were calculated for binary outcomes, mean differences for continuous
outcomes. We planned to explore the effects of age, specific anaesthesia regimen,
depth of anaesthesia and intraoperative haemodynamic events through subgroup
analyses. RESULTS: Six RCTs were included. The incidence of postoperative
delirium did not differ between groups (4 trials, 557 patients, RR 0.83, 95% CI
[0.25, 2.80]), but patients receiving ketamine seemed at lower risk of POCD (3
trials, 163 patients, RR 0.34, 95% CI [0.15, 0.73]). However, both analyses
presented limitations. Therefore, the quality of the evidence (GRADE) was deemed
low (postoperative delirium) and very low (POCD). CONCLUSION: The effect of
ketamine on postoperative delirium remains unclear but its administration may
offer some protection towards POCD. Large, well-designed randomised trials are
urgently needed to further clarify the efficacy of ketamine on neurocognitive
outcomes.
PMID- 29947092
TI - Visualization of nerve fibers around the carotid bifurcation with use of a 9.4
Tesla microscopic magnetic resonance diffusion tensor imaging with tractography.
AB - BACKGROUND: Precise imaging of nerves have been challenging in the head and neck
region, mainly due to low spatial resolution. Here, we investigated how nerves in
the head and neck region could be visualized using an ultra-high magnetic field
MR system. METHODS: We used formol-carbol-fixed human cadaveric necks and
obtained MR diffusion tensor images (DTIs) using a 9.4 Tesla (T) ultra-high
magnetic field MR system. Afterward, we prepared tissue sections and checked the
anatomic relationships between the neurons and the carotid artery in order to
confirm that the visualized fibers are indeed neuron fibers. RESULTS: We were
able to identify nerves, including the vagus nerve, the hypoglossal nerve, and
the spinal-accessory nerve. Hematoxylin-eosin stained histological sections
confirmed neuron fibers in the same anatomic position. CONCLUSION: This technique
has the feasibility to be applied for a more accurate anatomic understanding,
maybe even close to a histological level.
PMID- 29947093
TI - Photoinduced Cleavage and Hydrolysis of o-Nitrobenzyl Linker and Covalent Linker
Immobilization in Gelatin Methacryloyl Hydrogels.
AB - Light-induced release systems can be triggered remotely and are of interest for
many controlled release applications due to the possibility for spatio-temporal
release control. In this study a biotin-functionalized photocleavable macromer is
incorporated with an o-nitrobenzyl moiety into gelatin methacryloyl(-acetyl)
hydrogels via radical cross-linking. Stronger immobilization of streptavidin
coupled horseradish peroxidase occurs in linker-functionalized hydrogels compared
to pure gelatin methacryloyl(-acetyl) hydrogels, and a controlled release of the
streptavidin conjugate upon UV-irradiation is possible. Liquid chromatography
coupled to mass spectrometry (LC-MS) analysis of aqueous linker solutions allows
the identification of the main cleavage products and the cleavage kinetics. Thus,
it is shown that a significant hydrolysis of the linker occurs at 37 degrees C.
Nevertheless the system reported here is a promising controlled release scaffold
for proteins and application in tissue engineering, if background releases of the
immobilized drug are tolerable.
PMID- 29947094
TI - Distinct neural substrates for visual short-term memory of actions.
AB - Fundamental theories of human cognition have long posited that the short-term
maintenance of actions is supported by one of the "core knowledge" systems of
human visual cognition, yet its neural substrates are still not well understood.
In particular, it is unclear whether the visual short-term memory (VSTM) of
actions has distinct neural substrates or, as proposed by the spatio-object
architecture of VSTM, shares them with VSTM of objects and spatial locations. In
two experiments, we tested these two competing hypotheses by directly contrasting
the neural substrates for VSTM of actions with those for objects and locations.
Our results showed that the bilateral middle temporal cortex (MT) was
specifically involved in VSTM of actions because its activation and its
functional connectivity with the frontal-parietal network (FPN) were only
modulated by the memory load of actions, but not by that of objects/agents or
locations. Moreover, the brain regions involved in the maintenance of spatial
location information (i.e., superior parietal lobule, SPL) was also recruited
during the maintenance of actions, consistent with the temporal-spatial nature of
actions. Meanwhile, the frontoparietal network (FPN) was commonly involved in all
types of VSTM and showed flexible functional connectivity with the domain
specific regions, depending on the current working memory tasks. Together, our
results provide clear evidence for a distinct neural system for maintaining
actions in VSTM, which supports the core knowledge system theory and the domain
specific and domain-general architectures of VSTM.
PMID- 29947095
TI - Peak exercise stroke volume effects on cognitive impairment in community-dwelling
people with preserved ejection fraction.
AB - AIMS: The association of vascular dysfunction and amyloid beta deposition
attracted attentions for its relationship with cognitive decline. Previous
studies show the correlation between the declined cardiac function and the
cognitive impairment. In the present study, we analysed the association between
cognitive functions and cardiac parameters in community-dwelling people with
preserved ejection fraction without heart failure. METHODS AND RESULTS: Subjects
were 108 Japanese community-dwelling middle-aged and older adults with preserved
ejection fraction (25 men and 83 women; mean age 74.7 years). Cardiac functional
parameters at rest were assessed with B-type natriuretic peptide and
echocardiography. The cardiopulmonary exercise test was used to test these
parameters during exercise. Cognitive function was assessed with the Japanese
version of the Montreal Cognitive Assessment (MoCA-J). Other indices were
assessed biochemically, physiologically, and physically. There were significant
correlations between MoCA-J score and age (r = -0.388), peak oxygen uptake (VO2 ,
r = 0.201), peak VO2 /heart rate (HR, r = 0.243), peak VO2 /weight (r = 0.244),
peak metabolic equivalents (r = 0.244), usual walking speed (r = -0.200), and the
Timed Up and Go test (r = -0.230). Multiple linear regression analysis showed
peak VO2 /HR was an independent determinant of MoCA-J score after adjusting for
potential confounders (B = 0.424). After 6 months of exercise training with 64
subjects, we found that the per cent change of peak VO2 /HR was related to the
per cent change of MoCA-J score (r = 0.296). CONCLUSIONS: These results suggested
that peak VO2 /HR (an index of stroke volume at peak exercise) might be
associated with cognitive impairment based on the vascular cascade hypothesis.
PMID- 29947097
TI - CrossTalk opposing view: the hypoxic ventilatory response does not include a
central, excitatory hypoxia sensing component.
PMID- 29947096
TI - Echoes of Early Life: Recent Insights From Mathematical Modeling.
AB - In the last decades, developmental origins of health and disease (DOHaD) has
emerged as a central framework for studying early-life effects, that is, the
impact of fetal and early postnatal experience on adult functioning. Apace with
empirical progress, theoreticians have built mathematical models that provide
novel insights for DOHaD. This article focuses on three of these insights, which
show the power of environmental noise (i.e., imperfect indicators of current and
future conditions) in shaping development. Such noise can produce: (a)
detrimental outcomes even in ontogenetically stable environments, (b) individual
differences in sensitive periods, and (c) early-life effects tailored to
predicted future somatic states. We argue that these insights extend DOHaD and
offer new research directions.
PMID- 29947098
TI - Embryonic effects of an environmentally relevant PCB mixture in the domestic
chicken.
AB - Studies were conducted to develop methods to assess the effects of a complex
mixture of polychlorinated biphenyls (PCBs) in the domestic chicken (Gallus
domesticus). Treatments were administered by egg injection to compare embryonic
effects of an environmentally relevant PCB congener mixture in the domestic
chicken over a range of doses. Chicken eggs were injected with the PCB mixture
with a profile similar to that found in avian eggs collected on the upper Hudson
River, New York, USA, at doses that spanned 0 to 98 MUg/g egg. Eggs were hatched
in the laboratory to ascertain hatching success. In the domestic chicken, the
median lethal dose was 0.3 MUg/g. These data demonstrate adverse effects of an
environmentally relevant PCB mixture and provide the basis for further work using
in vitro and other models to characterize the potential risk to avian
populations. Environ Toxicol Chem 2018;37:2513-2522. (c) 2018 SETAC.
PMID- 29947100
TI - Does angiotensin II regulate parathyroid hormone secretion or not?
PMID- 29947101
TI - Nursing students' experiences of using a smart phone application for a physical
assessment course: A qualitative study.
AB - AIM: It is important that nurses possess adequate clinical skills so that the
patient receives safe and competent care. Smart phone applications (apps) can
promote active learning and the long-term retention of knowledge of undergraduate
students. Therefore, the aim of this study was to explore the thoughts and
experiences of nursing students who received a smart phone, app-based physical
assessment educational intervention. METHODS: A qualitative descriptive approach
with in-depth interviews was considered as suitable to obtain a comprehensive
understanding of students' experiences of a smart phone-enabled physical
assessment course. RESULTS: Based on interviews with 16 nursing students
following the intervention, five themes were derived from the analysis of the
interview transcripts: "the APP's physical assessment scenarios are very close to
real-life clinical situations," "watching physical assessment videos over the APP
is a quick way to learn what to do," "the APP is a new way of learning that
enhances thinking and reflection," "some nursing students felt that it was out of
their depth to analyze the scenarios in the APP," and "the APP needs enhancements
in stability and interactivity." CONCLUSION: The findings of this study showed
the mobile app as an effective learning aid that promoted transferability of the
nursing students' knowledge and past experience. With the help of the APP, the
teachers could offer timely guidance to the students.
PMID- 29947099
TI - Efficacy and safety of dapagliflozin or dapagliflozin plus saxagliptin versus
glimepiride as add-on to metformin in patients with type 2 diabetes.
AB - OBJECTIVE: To compare the efficacy and safety of dapagliflozin and dapagliflozin
plus saxagliptin vs glimepiride as add-on to metformin in patients with type 2
diabetes. RESEARCH DESIGN AND METHODS: This 52-week, multicentre, double-blind,
active-controlled study (NCT02471404) randomized (1:1:1) patients (n = 939; HbA1c
7.5%-10.5%) on metformin monotherapy (>=1500 mg/day) to add-on dapagliflozin 10
mg, dapagliflozin 10 mg plus saxagliptin 5 mg, or glimepiride 1 to 6 mg
(titrated). The primary efficacy end point was change in HbA1c from baseline to
Week 52. RESULTS: Baseline mean age, diabetes duration and HbA1c were 58.4 years,
7.0 years and 8.3%, respectively. Adjusted mean HbA1c change from baseline was
1.20% with dapagliflozin plus saxagliptin and -0.82% with dapagliflozin, vs
0.99% with glimepiride (mean dose at Week 52, 4.6 mg). Changes in body weight (
3.2 kg and -3.5 kg vs +1.8 kg) and systolic blood pressure (SBP; -6.4 mm Hg and
5.6 mm Hg vs -1.6 mm Hg) were significantly greater with dapagliflozin plus
saxagliptin and dapagliflozin than with glimepiride. FPG decreased significantly
with dapagliflozin plus saxagliptin compared with glimepiride (-2.1 mmol/L vs
1.5 mmol/L) and was similar with dapagliflozin (-1.6 mmol/L) compared with
glimepiride. Confirmed incidence of hypoglycaemia was lower with dapagliflozin
regimens than with glimepiride (0 and 1 vs 13 patients) and fewer patients
required rescue. Genital infections were more frequent with dapagliflozin; other
AE profiles were similar. CONCLUSIONS: Dapagliflozin, saxagliptin and metformin
improved glycaemic control compared with glimepiride plus metformin; add-on of
dapagliflozin alone showed efficacy similar to that of glimepiride. Both
dapagliflozin regimens decreased body weight and SBP, with a lower incidence of
hypoglycaemia compared with glimepiride.
PMID- 29947102
TI - Fully Bioabsorbable Natural-Materials-Based Triboelectric Nanogenerators.
AB - Implantable medical devices provide an effective therapeutic approach for
neurological and cardiovascular diseases. With the development of transient
electronics, a new power source with biocompatibility, controllability, and
bioabsorbability becomes an urgent demand for medical sciences. Here, various
fully bioabsorbable natural-materials-based triboelectric nanogenerators (BN
TENGs), in vivo, are developed. The "triboelectric series" of five natural
materials is first ranked, it provides a basic knowledge for materials selection
and device design of the TENGs and other energy harvesters. Various triboelectric
outputs of these natural materials are achieved by a single material and their
pairwise combinations. The maximum voltage, current, and power density reach up
to 55 V, 0.6 uA, and 21.6 mW m-2 , respectively. The modification of silk fibroin
encapsulation film makes the operation time of the BN-TENG tunable from days to
weeks. After completing its function, the BN-TENG can be fully degraded and
resorbed in Sprague-Dawley rats, which avoids a second operation and other side
effects. Using the proposed BN-TENG as a voltage source, the beating rates of
dysfunctional cardiomyocyte clusters are accelerated and the consistency of cell
contraction is improved. This provides a new and valid solution to treat some
heart diseases such as bradycardia and arrhythmia.
PMID- 29947103
TI - Plasma lecithin:cholesterol acyltransferase and phospholipid transfer protein
activity independently associate with nonalcoholic fatty liver disease.
AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent
condition which contributes to atherogenic apolipoprotein B dyslipoproteinemias.
Lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein
(PLTP) are both synthesized by the liver and are important in lipid metabolism.
Here, we interrogated the impact of NAFLD on plasma LCAT and PLTP activities.
METHODS: Plasma LCAT activity (exogenous substrate assay) and PLTP activity
(phospholipid vesicles-HDL assay) were determined in 348 subjects (279 men; 81
subjects with type 2 diabetes (T2DM); 123 with metabolic syndrome (MetS)). A
Fatty Liver Index (FLI) >=60 was used as a proxy of NAFLD. Insulin resistance was
determined by homoeostasis model assessment (HOMA-IR). RESULTS: A total of 147
participants had an FLI >=60 coinciding with T2DM and MetS (P < 0.001 for each).
Plasma LCAT activity and PLTP activity were on average 12% and 5% higher,
respectively, in subjects with an FLI >= 60 (P < 0.001 for each). In age- and sex
adjusted partial linear regression analysis, LCAT activity and PLTP activity were
positively related to various obesity measures and HOMA-IR (P < 0.001 for each).
In multivariable linear regression analyses adjusted for age and sex, LCAT
activity was associated with an FLI >= 60 independent of T2DM and MetS, the
waist/hip ratio, or HOMA-IR (beta = 0.307 to 0.366, P < 0001 for all models).
PLTP activity was also associated with an FLI >= 60 independent of these
variables (beta = 0.151 to 0223, P = 0.013 to 0.001). CONCLUSION: NAFLD, as
inferred from an FLI>=60, confers higher plasma LCAT and to a lesser extent PLTP
activity, even when taking account of T2DM, MetS, central obesity and insulin
resistance.
PMID- 29947104
TI - A young man with necrotic skin lesions.
PMID- 29947105
TI - Metal Deposition on a Self-Generated Microfibril Network to Fabricate Stretchable
Tactile Sensors Providing Analog Position Information.
AB - Stretchable conductors and sensors have attracted great attention for use in
electronic skin and healthcare monitoring. Despite the development of many
stretchable conductors, there are still very few studies that utilize the
conventional methods making electrodes and circuits used in current industry. A
method is proposed to fabricate a stretchable electrode pattern and a stretchable
tactile sensor by simply depositing linear metal lines through a mask on a
stretchable substrate. A method is developed of a self-generating microfibril
network on the surface of stretchable block copolymer substrates. The formation
mechanism of the microfibril network is studied with finite element method
simulations. Metals (Au and Ag nanowires) are deposited directly on the substrate
through a patterned mask. This study shows that strain-insensitive circuit and
strain-sensitive sensor can be fabricated in a controlled way by adjusting the
thickness of the deposited metal, which makes it easy to fabricate a tactile
sensor by metal deposition. Also, by using the characteristic that the sensor has
different sensitivity depending on the line pattern width, a novel sensor
structure simultaneously providing analog-type position information and pressure
value is proposed.
PMID- 29947106
TI - Impact of acute stress on itch sensation and scratching behaviour in patients
with atopic dermatitis and healthy controls.
AB - BACKGROUND: Patients with atopic dermatitis (AD) often report that stress
aggravates their itch. However, no study has investigated if and how acute stress
influences itch sensation and scratching behaviour in these patients. OBJECTIVES:
We evaluated the impact of acute stress on experimentally induced cowhage itch
perception and scratching behaviour in 16 healthy subjects and 15 patients with
AD. METHODS: The Trier Social Stress Test (TSST) was used to induce acute stress.
The itch sensation, provoked by applying cowhage to the forearms, and off-site
scratching behaviour (not directed at the cowhage application site) were compared
before and after performing the TSST or the control condition (watching a video
of landscape scenes). RESULTS: In patients with AD, stress induced by TSST caused
a significant reduction of cowhage-evoked itch but significantly increased off
site scratching behaviour. Such changes in itch perception and scratching
behaviour were not observed in healthy controls. In addition, a significant
positive correlation was noted between stress induced by TSST and clinical
severity of eczema. CONCLUSIONS: We speculate that psychological stress increases
spontaneous scratching in patients with AD, which may enhance the vicious cycle
of itching and scratching, resulting in aggravation of the skin eczema. These
results provide new insights on the mechanism of acute stress-related
exacerbation of itch in patients with AD.
PMID- 29947107
TI - Comparison of time-matched aerobic, resistance, or concurrent exercise training
in older adults.
AB - A supervised 12-week intervention of time-matched aerobic vs resistance versus
concurrent exercise training was employed to investigate mode- and time course
specific effects of exercise training in older adults. Community-dwelling men and
women (n = 84; M/F, 45/39; 69.3 +/- 3.5 years; 26.4 +/- 3.8 kg m-2 ) were
randomly assigned (n = 21 each) to either non-exercise control (CON), aerobic
exercise only (AER), resistance exercise only (RES), or concurrent aerobic and
resistance exercise (CEX). Training groups trained three times per week, each
performing 72 minutes of active exercise time per week. Body composition,
physical and cognitive function, and markers of metabolic health were assessed
before (PRE), and after 6 (MID) and 12 (POST) weeks of exercise training. Hand
grip strength, 1RM chest press, and arm LBM were improved by both RES and CEX,
but not AER. Aerobic fitness increased in AER and RES, but not CEX. Cognitive
function improved in all groups, but occurred earlier (ie, at MID) in AER. CEX
improved gait speed and lower limb strength and reduced trunk fat compared to
either AER or RES. Leg LBM was unchanged in any group. Temporal patterns were
observed as early as 6 weeks of training (gait speed, upper and lower limb
strength, aerobic fitness), whereas others were unchanged until 12 weeks (hand
grip strength, timed up-and-go, sit-to-stand). Compared to either aerobic or
resistance exercise training alone, concurrent exercise training is as
efficacious for improving a range of health-related parameters and is more
efficacious for increasing gait speed and lower limb strength, and decreasing
trunk fat in older adults.
PMID- 29947108
TI - Association of E-cadherin methylation with risk of nasopharyngeal cancer: A meta
analysis.
AB - BACKGROUND: Various studies have assessed the association between E-cadherin
methylation and risk of nasopharyngeal cancer (NPC) but the conclusion remains
unclear. This meta-analysis was conducted to evaluate the effects of E-cadherin
methylation on the incidence and clinicopathological characteristics of NPC.
METHODS: Ten studies published up to June 30, 2016, were collected. Odds ratios
(ORs) with corresponding confidence intervals (CIs) were calculated and
summarized, respectively. RESULTS: The E-cadherin methylation in NPC was
significantly higher than those in normal groups (OR 16.23; 95% CI 8.34-31.60; P
< .001). Ethnicity-stratified analysis indicated that E-cadherin methylation was
strongly correlated with NPC among both Asians (OR 16.98; 95% CI 8.45-34.14; P <
.001) and North Africans (OR 10.67; 95% CI 1.21-93.72; P = .033). However,
further analysis showed that E-cadherin methylation was not strongly associated
with clinicopathological feathers in patients with NPC. CONCLUSION: The E
cadherin methylation is strongly associated with the incidence of NPC, which can
serve as an effective biomarker for early detection of NPC.
PMID- 29947109
TI - High-density mapping for catheter ablation of premature ventricular complexes
originating from left ventricular papillary muscles: A case series.
AB - PURPOSE: Ablation of premature ventricular complexes (PVCs) originating from left
sided papillary muscles is challenging. We tested a new approach by performing
high-density mapping of PVC. METHODS AND RESULTS: We used a 20-pole deflectable
spiral catheter during ablation procedures in four consecutive patients. Three
presented with mitral valve prolapse, one with dilated cardiomyopathy. PVC burden
was 24 +/- 13%. The procedures lasted 182 +/- 55.4 minutes, including 10 +/- 3.2
minutes of radiofrequency. In all patients, mapping evidenced internal primary
activation relative to the left ventricle shell (mean distance 21.3 +/- 5.1 mm).
Endocavitary prematurity was -38.3 +/- 4.8 ms. Primary ablation success was
achieved for all patients. CONCLUSIONS: High-density mapping of the papillary
muscles in the left ventricle using a spiral catheter may be feasible. We
identified the PVC foci away from the left ventricular shell. This consolidates
the assumption for the origin of these ectopic beats at the junction between the
chordae tendineae and the papillary muscles.
PMID- 29947110
TI - Adverse effects of a single dose of gentamicin.
PMID- 29947111
TI - Prognosis of subglottic carcinoma: Is it really worse?
AB - It is traditionally accepted that subglottic carcinoma has a worse prognosis than
tumors arising in other subsites of the larynx, owing to its tendency to present
in advanced stages, with a high incidence of cartilage invasion and
extralaryngeal spread. The incidence of subglottic carcinoma varies among series,
mainly because there is no uniform definition of the upper boundary of the
subglottis. The extent of the tumor may be difficult to define because subglottic
carcinoma may spread through the submucosa without visible mucosal changes. There
is also a rich lymphatic network in the subglottis draining to the prelaryngeal
and paratracheal lymph nodes, which are usually not involved by cancers arising
in other laryngeal subsites. Current literature data indicates that early-stage
subglottic carcinoma can be treated using radiotherapy or chemoradiotherapy with
high locoregional control and survival rates. In advanced stage subglottic
carcinoma, combination of surgery followed by radiotherapy or chemoradiotherapy
resulted in comparable outcomes, as in advanced carcinomas from the rest of the
larynx. Stage for stage, it is likely that the prognosis for subglottic carcinoma
and of glottic and supraglottic cancers is similar.
PMID- 29947112
TI - Serum adiponectin and cardiovascular disease: mechanism of the association.
PMID- 29947113
TI - Use of Endoglycosidase H as a diagnostic tool for MAN1B1-CDG patients.
AB - Congenital disorders of glycosylation (CDG) are heterogeneous group of genetic
protein and lipid glycosylation abnormalities. With some 33 reported patients,
MAN1B1-CDG belongs to the more frequent causes of CDG-II. MAN1B1 encodes an
alpha1,2-mannosidase that removes the terminal mannose residue from the middle
branch. Several methods have been proposed to characterize the glycosylation
changes. In MAN1B1-CDG, the abnormal accumulating N-glycan structures are mostly
absent or found in trace amounts in total human serum. To overcome this issue, in
this study, we present a straightforward procedure based on the use of Endo-beta
N-acetylglucosaminidase H to easily diagnose MAN1B1-CDG patients and mannosidase
defects.
PMID- 29947114
TI - Intraoperative ultrasound assistance for the surgical removal of lost
intrauterine device.
AB - A 45-year woman, carrying an IUD for 2 years, was referred to our emergency unit
for pelvic pain and bleeding. At vaginal examination, the strings of the IUD were
not identified. Laboratory parameters were unremarkable. The abdominal
radiography documented the presence of IUD in the abdominal cavity (FIG.1).
During laparoscopy, the surgeon was unable to localize the IUD and an
intraoperative ultrasound examination was requested. Using a sterile
transabdominal probe the presence of a tubular hyperechoic structure in the
abdominal cavity was confirmed and a precise localization within the bowel loops
was defined (FIG 2 and Video 1). This article is protected by copyright. All
rights reserved.
PMID- 29947115
TI - Gastrointestinal: Retained sponge presenting as an unusual intra-abdominal mass.
PMID- 29947116
TI - The crucial but underrepresented role of philosophy in conservation science
curricula.
AB - Article impact statement: Normative scientists must be trained in current
thinking of the philosophy that underlies their fields, an issue not fully
realized in conservation.
PMID- 29947117
TI - Analysis of terizidone in plasma using HPLC-UV method and its application in a
pharmacokinetic study of patients with drug-resistant tuberculosis.
AB - A chromatographic method has been developed and validated for the first time for
analysis of terizidone in plasma. Terizidone was extracted from plasma by protein
precipitation using a mixture of acetonitrile and methanol (1:1, v/v). The
chromatographic separation was achieved with a gradient of acetonitrile and water
both containing 0.1% formic acid on a Supelco Discovery(r) HS C18 (150 * 4.6 mm,
5 MUm) reversed-phase column. Propranolol was used as the internal standard. The
total run-time was 18 min. The calibration standard concentrations ranged between
3.125 and 200 MUg/mL and calibration curves were linear with coefficient of
determination values in the range of 0.9988-0.9999. The inter- and intra-day
assay precision (percentage relative standard error) was <15% while mean accuracy
was 107%. The mean extraction efficiencies of terizidone and IS were 76 and 89%,
respectively. The validation results demonstrated that the method was selective
and sensitive, and that terizidone was stable under the studied conditions. The
method was successfully applied in a population pharmacokinetic study. The mean
plasma concentration of terizidone in patients at all sampling time points was
51.8 +/- 28 MUg/mL. The method was simple, cheap and hence suitable for
therapeutic drug monitoring of terizidone.
PMID- 29947118
TI - Alterations in the nucleocytoplasmic transport in apoptosis: Caspases lead the
way.
AB - Apoptosis is a mode of regulated cell death that is indispensable for the
morphogenesis, development and homeostasis of multicellular organisms. Caspases
are cysteine-dependent aspartate-specific proteases, which function as initiators
and executors of apoptosis. Caspases are cytosolic proteins that can cleave
substrates located in different intracellular compartments during apoptosis. Many
years ago, the involvement of caspases in the regulation of nuclear changes, a
hallmark of apoptosis, was documented. Accumulated data suggest that apoptosis
associated alterations in nucleocytoplasmic transport are also linked to caspase
activity. Here, we aim to discuss the current state of knowledge regarding this
process. Particular attention will be focused on caspase nuclear entry and their
functions in the demolition of the nucleus upon apoptotic stimuli.
PMID- 29947119
TI - Comparison of wiping and rinsing techniques after oral care procedures in
critically ill patients during endotracheal intubation and after extubation: A
prospective cross-over trial.
AB - AIM: Endotracheal intubation of critically ill patients increases the risk of
aspiration pneumonia, which can be reduced by regular oral care. However, the
rinsing of the residual oral contaminants after mechanical cleaning carries the
risk of aspirating the residue during the intubation period. Removing the
contaminants by wiping with mouth wipes could be an alternative to rinsing with
water because of no additional fluid. This study tested: (i) the amount of oral
bacteria during endotracheal intubation and after extubation; and (ii) the
changes in the bacterial count during oral care procedures. METHODS: Thirty-five
mechanically ventilated patients in the intensive care unit were enrolled. The
amount of bacteria on the dorsal tongue surface was counted before and following
oral care and then after the elimination of contaminants either by rinsing with
water and suctioning or by wiping with mouth wipes. The oral bacterial amount was
compared statistically between the intubation and extubation status and among set
time points during the oral care procedure. RESULTS: The oral bacterial count was
significantly decreased after extubation. During the oral care procedure, the
oral bacterial amount was significantly lower after eliminating the contaminants
either by rinsing or wiping, with no remarkable difference between the
elimination techniques. CONCLUSIONS: The findings suggest that the oral bacterial
amount is elevated during endotracheal intubation, which could increase the risk
of aspiration pneumonia. The significant reduction in the bacterial count by
wiping indicates that it might be a suitable alternative to rinsing for
mechanically ventilated patients.
PMID- 29947120
TI - 'Eminence based medicine' and the Goldilocks principle: Authors' reply to
'Working hours of obstetrics and gynaecology trainees in Australia and New
Zealand'.
PMID- 29947121
TI - Is conservative treatment an effective option for pilonidal sinus disease in
children?
AB - Pilonidal sinus disease (PSD) is associated with a complex disease process in
children, and its management remains controversial. There are a few published
studies on PSD in the paediatric literature; therefore, we present our experience
of conservatively treating PSD in children. This study involved a retrospective
review with telephone follow up. All children diagnosed with PSD in 2012 to 2017
were identified at the outpatient clinic of the Department of Paediatric Surgery.
All patients initially underwent conservative treatment (meticulous hair removal,
improved perianal hygiene, warm sitz baths, and drainage for abscess). Data
collection included demographics, type of management, recurrence, presence of
infection, and total healing time. In the study period, 29 children were
identified. Their mean age was 14.94 +/- 1.09 (range: 12-16) years, and 51.7%
were girls. The mean length of follow up was 8.34 +/- 6.36 (range: 1-25) months.
Complete healing occurred in 79.3% of patients. Recurrence was evident in 12% of
patients. Four patients underwent surgery. PSD is being seen in children more
frequently in recent years. Conservative treatment may be the recommended initial
approach for PSD in children.
PMID- 29947122
TI - Heart and heart-liver transplantation in adults with failing Fontan physiology.
AB - BACKGROUND: As the population of patients with a Fontan palliation grows so does,
the number of patients with cardiac failure necessitating orthotopic heart
transplant (OHT) and combined heart-liver transplant (CHLT). There is recent
evidence that current era cardiac transplant in Fontan patients has improved
outcomes, but most studies have a preponderance of pediatrics patients in their
cohorts. We examine our institutional experience with adult OHT and CHLT
transplantation for failed Fontan physiology. METHODS AND RESULTS: Retrospective
analysis of patients at the Ahmanson/UCLA Adult Congenital Heart Disease Center
who underwent OHT or CHLT for failing Fontan physiology from January 1, 2002 to
May 31, 2017. We identified 20 patients with single-ventricle physiology and
Fontan palliation who underwent OHT or CHLT. The median age was 29.5 years (range
19-44). Five patients underwent CHLT because of biopsy proven hepatic cirrhosis.
The median length of hospital stay was 23 days (range 8-76) post-OHT and 51 days
(range 26-77) post-CHLT. During a median follow-up of 56 months (range 2-178),
there was one mortality occurring at 34 months post-OHT due to coronary
vasculopathy. Most frequent early postoperative complications included bleeding
and infection (55% and 20%, respectively) and surgical reintervention for
bleeding complications (n = 8, 40%). One CHLT patient experienced clinically
significant hepatic rejection requiring admission and steroid treatment.
CONCLUSIONS: Despite inherent risks and complexities of OHT or CHLT in patients
with a failed Fontan, transplant is a reasonable therapy. Peri- and postoperative
complications are common and may require surgical reintervention. Continued
observation of practices and unifying themes may help improve patient selection,
pre- and postoperative treatment and ultimately outcomes.
PMID- 29947123
TI - Unprecedented 34 S-enrichment of pyrite formed following microbial sulfate
reduction in fractured crystalline rocks.
AB - In the deep biosphere, microbial sulfate reduction (MSR) is exploited for energy.
Here, we show that, in fractured continental crystalline bedrock in three areas
in Sweden, this process produced sulfide that reacted with iron to form pyrite
extremely enriched in 34 S relative to 32 S. As documented by secondary ion mass
spectrometry (SIMS) microanalyses, the delta34 Spyrite values are up to +1320/00V
CDT and with a total range of 1860/00. The lightest delta34 Spyrite values (
540/00) suggest very large fractionation during MSR from an initial sulfate with
delta34 S values (delta34 Ssulfate,0 ) of +14 to +280/00. Fractionation of this
magnitude requires a slow MSR rate, a feature we attribute to nutrient and
electron donor shortage as well as initial sulfate abundance. The superheavy
delta34 Spyrite values were produced by Rayleigh fractionation effects in a
diminishing sulfate pool. Large volumes of pyrite with superheavy values (+120 +/
150/00) within single fracture intercepts in the boreholes, associated heavy
average values up to +750/00 and heavy minimum delta34 Spyrite values, suggest
isolation of significant amounts of isotopically light sulfide in other parts of
the fracture system. Large fracture-specific delta34 Spyrite variability and
overall average delta34 Spyrite values (+11 to +160/00) lower than the
anticipated delta34 Ssulfate,0 support this hypothesis. The superheavy pyrite
found locally in the borehole intercepts thus represents a late stage in a much
larger fracture system undergoing Rayleigh fractionation. Microscale Rb-Sr dating
and U/Th-He dating of cogenetic minerals reveal that most pyrite formed in the
early Paleozoic era, but crystal overgrowths may be significantly younger. The
delta13 C values in cogenetic calcite suggest that the superheavy delta34 Spyrite
values are related to organotrophic MSR, in contrast to findings from marine
sediments where superheavy pyrite has been proposed to be linked to anaerobic
oxidation of methane. The findings provide new insights into MSR-related S
isotope systematics, particularly regarding formation of large fractions of 34 S
rich pyrite.
PMID- 29947124
TI - Ascertainment and validation of major bleeding events in a primary care database.
AB - PURPOSE: The purpose of the study is to evaluate the impact of validation on the
identification of major bleeding events in The Health Improvement Network (THIN)
database in patients receiving anticoagulant therapy. METHODS: Patients aged 2 to
89 years with a first prescription for an anticoagulant (rivaroxaban or warfarin)
between 2012 and 2015 were identified in THIN. Major bleeding events, defined as
bleeding events necessitating hospitalization or referral to accident and
emergency services or a specialist clinic, were identified using a 2-step
ascertainment process based on read codes only, and then validated using a 2-step
process requiring manual review of patients' records. RESULTS: The positive
predictive value for the ascertainment of major intracranial (IC) bleeds using
only read codes was 96.9%, compared with 70.4% for gastrointestinal (GI) bleeds
and 64.1% for urogenital (UG) bleeds. The incidence rate of major IC bleeding
events was therefore similar when it was calculated before and after validation
(0.32 per 100 person-years and 0.31 per 100 person-years, respectively). The
incidence rate of major GI bleeds identified using read codes alone was reduced
following validation from 2.05 to 0.94 per 100 person-years, and that of major UG
bleeds decreased from 2.45 to 1.11 per 100 person-years. CONCLUSIONS: Major GI
and UG bleeding events ascertained from THIN using read codes require validation
using additional information to prevent outcome misclassification. The absence of
validation may lead to overestimated incidence rates of major bleeding for GI and
UG bleeds.
PMID- 29947125
TI - International Forum on typing and matching strategies in patients on anti-CD38
monoclonal therapy.
PMID- 29947126
TI - Changes in urethral mobility and configuration after prolapse repair.
AB - OBJECTIVES: To evaluate changes in urethral mobility and configuration after
prolapse repair. METHODS: This is a retrospective study on 92 patients before and
after surgery for pelvic organ prolapse (POP) without incontinence surgery
between 2005 and 2016. All were assessed with an interview, POP-Q and translabial
4D ultrasound. Urethral mobility was evaluated using the urethral motion profile
(UMP) where x and y coordinates of 6 equidistant points along the length of
urethra were determined both at rest and on Valsalva, relative to the
posteroinferior margin of the pubis. Urethral kinking was measured by placing
tangents distal and proximal to any visually identified change in urethral axis.
Imaging data obtained before and after prolapse surgery were compared using
paired-t test and Wilcoxon Rank Test. RESULTS: Mean age was 58 years, mean follow
up 5.8 months. Prolapse symptoms had resolved in 85% of patients. A highly
significant reduction in urethral mobility and urethral kinking was seen after
surgery (all p <= 0.001). Similar changes were observed after anterior +/- apical
repair without concomitant posterior repair (n = 23, all p < 0.05). CONCLUSIONS:
POP surgery was significantly associated with 'straightening' of the urethra and
reduction in urethral mobility. The effect seems to be largely due to cystocele
repair. This article is protected by copyright. All rights reserved.
PMID- 29947127
TI - Can we risk transplantation across positive complement-dependent cytotoxicity
crossmatches in pediatric patients?
PMID- 29947128
TI - Trapeziometacarpal stabilization through dorsoradial ligament reconstruction: An
early post-surgery in vivo biomechanical analyses.
AB - Ligament reconstruction can provide pain relief in patients with a painful,
unstable, pre-arthritic trapeziometacarpal (TMC) joint. Imbrication of the
dorsoradial ligament (DRL) has been proposed as a minimal invasive stabilization
technique. It requires less invasive surgery than an Eaton-Littler technique and
shows promising long-term clinical outcome. We used dynamic CT to objectively
review the effects of the imbrication. Four patients with pain and laxity at the
TMC joint, but without radiographic signs of osteoarthritis, were recruited.
Dynamic CT scans were made during active thumb abduction-adduction, flexion
extension, and two functional grip tasks using a radiolucent jig. Scans of the
patients were acquired before and 3 to 6 months after DRL reconstruction. Motion
of each bone in the articular chain of the thumb was quantified. In addition, we
mapped changes in the contact patterns between the articular facets during the
entire thumb motion. After DRL imbrication, we found no overall decrease in MC1
movement in three out of four patients. Furthermore, no increase in TMC joint
congruency, defined as proximity area size, was found for three out of four
patients. Pre- and post-operative differences in congruency across different
tasks were patient-dependent and relatively small. We demonstrated that, from a
biomechanical perspective, there is high variability in post-operative outcome
between patients that undergo identical surgical procedures performed by the same
surgeon. A post-operative decrease in range of motion, increase in joint
congruency or decrease in proximity area shift during thumb motion is not
omnipresent. (c) 2018 Orthopaedic Research Society. Published by Wiley
Periodicals, Inc. J Orthop Res.
PMID- 29947129
TI - Cause-specific mortality in patients with psoriasis and psoriatic arthritis.
AB - BACKGROUND: There are limited data regarding causes of mortality in patients with
psoriasis or psoriatic arthritis (PsA). OBJECTIVES: This retrospective cohort
study evaluated the risk and leading causes of mortality in patients with
psoriasis or PsA. METHODS: Individuals with a hospital-based diagnosis of PsA or
psoriasis were identified using the Danish National Patient Registry. Matched
control individuals were identified from the general population. The main outcome
measures were risk of death and cause-specific mortality in patients with
psoriasis or PsA. RESULTS: Death rates per 1000 patient-years (with 95%
confidence intervals) vs. controls were 22.3 (19.7-24.9) vs. 13.9 (11.8-16.0) for
patients with psoriasis and 10.8 (8.9-12.8) vs. 11.6 (9.6-13.6) for patients with
PsA. Survival, according to stratified hazard ratios (HRs), was significantly
lower in patients with psoriasis than in controls (HR 1.74, P < 0.001), but not
in patients with PsA (HR 1.06, P = 0.19). Significantly increased risk of death
was observed in patients with psoriasis vs. controls due to a number of causes;
the highest risks were observed for diseases of the digestive system; endocrine,
nutritional and metabolic diseases; and certain infectious and parasitic diseases
(HRs 3.61, 3.02 and 2.71, respectively). In patients with PsA, increased
mortality was observed only for certain infectious and parasitic diseases (HR
2.80) and diseases of the respiratory system (HR 1.46). Patients with psoriasis
died at a younger age than controls (mean age 71.0 vs. 74.5 years, P < 0.001).
CONCLUSIONS: Patients with severe psoriasis have increased mortality risk
compared with matched controls, due to a number of causes. Evidence to support an
increased risk for patients with PsA was less convincing.
PMID- 29947130
TI - Mediating role of neuroticism in the association between loneliness and cognitive
function among community-dwelling older adults.
AB - OBJECTIVE: The main aim of this study was to examine whether neuroticism mediates
the association between loneliness and cognitive function in older adults.
METHODS: This study involved 2322 representative community residents aged 60-92
years in Peninsular Malaysia. Cognition was measured by Mini-Mental State
Examination (MMSE), loneliness was assessed by three-item loneliness scale, and
neuroticism was assessed by the Short-Form Revised Eysenck Personality
Questionnaire. Hierarchical multiple linear regression and Sobel tests were used
for mediation analyses. RESULTS: Both loneliness (beta = -0.04, P = 0.03) and
neuroticism (beta = -0.07, P < 0.001) were negatively and significantly
associated with cognitive function, and most importantly, neuroticism mediated
the association between loneliness and cognition (from beta = -0.04, P = 0.03 to
beta = -0.03, P = 0.10). CONCLUSION: Neuroticism may be the potential mechanism
underlying the relationship between loneliness and cognitive function in older
persons.
PMID- 29947132
TI - A multi-scale model of the coronary circulation applied to investigate transmural
myocardial flow.
AB - Distribution of blood flow in myocardium is a key determinant of the localization
and severity of myocardial ischemia under impaired coronary perfusion conditions.
Previous studies have extensively demonstrated the transmural difference of
ischemic vulnerability. However, it remains incompletely understood how
transmural myocardial flow is regulated under in vivo conditions. In the present
study, a computational model of the coronary circulation was developed to
quantitatively evaluate the sensitivity of transmural flow distribution to
various cardiovascular and hemodynamic factors. The model was further
incorporated with the flow autoregulatory mechanism to simulate the regulation of
myocardial flow in the presence of coronary artery stenosis. Numerical tests
demonstrated that heart rate (HR), intramyocardial tissue pressure (Pim ), and
coronary perfusion pressure (Pper ) were the major determinant factors for
transmural flow distribution (evaluated by the subendocardial-to-subepicardial
(endo/epi) flow ratio) and that the flow autoregulatory mechanism played an
important compensatory role in preserving subendocardial perfusion against
reduced Pper . Further analysis for HR variation-induced hemodynamic changes
revealed that the rise in endo/epi flow ratio accompanying HR decrease was
attributable not only to the prolongation of cardiac diastole relative to
systole, but more predominantly to the fall in Pim . Moreover, it was found that
Pim and Pper interfered with each other with respect to their influence on
transmural flow distribution. These results demonstrate the interactive effects
of various cardiovascular and hemodynamic factors on transmural myocardial flow,
highlighting the importance of taking into account patient-specific conditions in
the explanation of clinical observations.
PMID- 29947134
TI - Prospective, randomized, double-blind assessment of topical bakuchiol and retinol
for facial photoageing.
AB - BACKGROUND: Bakuchiol is a phytochemical that has demonstrated cutaneous
antiageing effects when applied topically. Early studies have suggested that
bakuchiol is a functional analogue of topical retinoids, as both compounds have
been shown to induce similar gene expression in the skin and lead to improvement
of cutaneous photodamage. No in vivo studies have compared the two compounds for
efficacy and side-effects. OBJECTIVES: To compare the clinical efficacy and side
effect profiles of bakuchiol and retinol in improving common signs of cutaneous
facial ageing. METHODS: This was a randomized, double-blind, 12-week study in
which 44 patients were asked to apply either bakuchiol 0.5% cream twice daily or
retinol 0.5% cream daily. A facial photograph and analytical system was used to
obtain and analyse high-resolution photographs of patients at 0, 4, 8 and 12
weeks. Patients also completed tolerability assessment questions to review side
effects. During study visits, a board-certified dermatologist, blinded to study
group assignments, graded pigmentation and redness. RESULTS: Bakuchiol and
retinol both significantly decreased wrinkle surface area and hyperpigmentation,
with no statistical difference between the compounds. The retinol users reported
more facial skin scaling and stinging. CONCLUSIONS: Our study demonstrates that
bakuchiol is comparable with retinol in its ability to improve photoageing and is
better tolerated than retinol. Bakuchiol is promising as a more tolerable
alternative to retinol.
PMID- 29947133
TI - Triple Acceptors in a Polymeric Architecture for Balanced Ambipolar Transistors
and High-Gain Inverters.
AB - The exploration of novel molecular architectures is crucial for the design of
high-performance ambipolar polymer semiconductors. Here, a "triple-acceptors
architecture" strategy to design the ambipolar polymer DPP-2T-DPP-TBT is
introduced. The utilization of this architecture enables DPP-2T-DPP-TBT to
achieve deep-lying highest occupied molecular orbital (HOMO)/lowest unoccupied
molecular orbital (LUMO) levels of -5.38/-4.19 eV, and strong intermolecular
interactions, which are favorable for hole/electron injection and intermolecular
hopping through pi-stacking. All these factors result in excellent ambipolar
transport characteristics and promising applications in complementary-like
circuits for DPP-2T-DPP-TBT under ambient conditions with high hole/electron
mobilities and a gain value of up to 3.01/3.84 cm2 V-1 s-1 and 171, respectively,
which are among the best performances in ambipolar polymer organic thin-film
transistors and associated complementary-like circuits, especially in top-gate
device configuration with low-cost glass as substrates. These results demonstrate
that the "triple-acceptors architecture" strategy is an effective way for
designing high-performance ambipolar polymer semiconductors.
PMID- 29947131
TI - Genome-wide association analysis links multiple psychiatric liability genes to
oscillatory brain activity.
AB - Oscillatory activity is crucial for information processing in the brain, and has
a long history as a biomarker for psychopathology. Variation in oscillatory
activity is highly heritable, but current understanding of specific genetic
influences remains limited. We performed the largest genome-wide association
study to date of oscillatory power during eyes-closed resting
electroencephalogram (EEG) across a range of frequencies (delta 1-3.75 Hz, theta
4-7.75 Hz, alpha 8-12.75 Hz, and beta 13-30 Hz) in 8,425 subjects. Additionally,
we performed KGG positional gene-based analysis and brain-expression analyses.
GABRA2-a known genetic marker for alcohol use disorder and epilepsy-significantly
affected beta power, consistent with the known relation between GABAA interneuron
activity and beta oscillations. Tissue-specific SNP-based imputation of gene
expression levels based on the GTEx database revealed that hippocampal GABRA2
expression may mediate this effect. Twenty-four genes at 3p21.1 were significant
for alpha power (FDR q < .05). SNPs in this region were linked to expression of
GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex-genes that
were previously implicated in schizophrenia and bipolar disorder. In sum, we
identified several novel genetic variants associated with oscillatory brain
activity; furthermore, we replicated and advanced understanding of previously
known genes associated with psychopathology (i.e., schizophrenia and alcohol use
disorders). Importantly, these psychopathological liability genes affect brain
functioning, linking the genes' expression to specific cortical/subcortical brain
regions.
PMID- 29947135
TI - Evaluation of the synergistic effect with amino acids for enantioseparation of
basic drugs using capillary electrophoresis.
AB - The synergistic effect of two acidic amino acids, aspartic and glutamic acid, on
the electrophoretic enantioseparation of four basic drugs was evaluated in the
BGE containing a CD and at different pHs. Chlorpheniramine, hydroxyzine,
propranolol and tramadol were used as the basic model drugs. However, no
enantioseparations were achieved with a BGE containing sole amino acid, but the
combined use of an acidic amino acid and a CD showed improved enantioseparations
(synergistic effect) compared with the single CD system. The results demonstrated
that at optimized pH, the electrostatic interactions of the anionic amino acids
with the positively charged basic drugs could result in a decrease of the analyte
migration velocity and it consequently improved the enantioseparation. The
effective parameters such as the amino acid and chiral selector type and
concentration, buffer pH, applied voltage, and capillary temperature were
optimized. Favorable enantiomeric resolution and migration times of the model
drugs were achieved with a 100 mM phosphate buffer solution (pH 3.0) containing
5.0 mM HP-alpha-CD/HP-beta-CD and 20 mM aspartic acid with an 18 kV applied
voltage at 25 degrees C. 1 H NMR experiments were also carried out in a mixture
of an analyte and CD in the absence and presence of aspartic acid. The NMR
results were consistent with the results obtained by CE which showed the
synergistic effect of amino acid.
PMID- 29947136
TI - Evaluation of clinical decision support systems for diabetes care: An overview of
current evidence.
AB - BACKGROUND: Systematic reviews (SRs) have shown that clinical decision support
systems (CDSSs) have the potential to improve diabetes care. However, methods of
measuring and presenting outcomes are varied, and conclusions have been
inconsistent. In addition, the reporting and methodological quality in this field
is unknown, which could affect the integrity and accuracy of research. Therefore,
it is difficult to confirm whether CDSSs are effective in improving diabetes
care. OBJECTIVE: To comprehensively evaluate the effects of CDSS on diabetes care
and to examine the methodological and reporting qualities. METHODS: We searched
PubMed, EMBASE, and Cochrane Library from their inception to February 2017.
Systematic reviews investigating the effects of CDSS on diabetes care were
included. Outcomes were determined in advance and assessed separately for process
of care and patient outcomes. Methodological and reporting qualities were
assessed by AMSTAR and PRISMA, respectively. RESULTS: Seventeen SRs, consisting
of 222 unique randomized controlled trials and 102 nonrandomized controlled
trials, were included. Evidence that CDDS significantly impacted patient outcomes
was found in 32 of 102 unique studies of the 15 SRs that examined this effect
(31%). A significant impact of CDSS on process of care was found in 117 out of
143 unique studies of the 11 SRs that examined this effect (82%). Ratings for
overall scores of AMSTAR resulted in a mean score of 6.5 with a range of scores
from 3.5 to 10.0. Reporting quality related to methodological domains was
particularly incomplete. CONCLUSIONS: Clinical decision support systems improved
the quality of diabetes care by inconsistently improving process of care or
patient outcomes. There is evidence that CDSS for providing alerts, reminders, or
feedback to participants were most likely to impact diabetes care. Poor reporting
of methodological domains, together with qualitative or narrative methods to
combine findings, may limit the confidence in research evidence.
PMID- 29947137
TI - Airway granulocytes in severe preschool wheeze: Predictive of school-age asthma
attacks or disease protection.
PMID- 29947138
TI - Best of the Other Journals.
PMID- 29947140
TI - A new approach to oral allergen immunotherapy for food allergy?
PMID- 29947141
TI - Does transcutaneous electrical nerve stimulation have an antipruritic effect in
lichen planus? A randomized clinical trial.
AB - BACKGROUND: Lichen planus (LP) is a moderately prevalent inflammatory disorder
that affects the skin and the oral mucosa, leading to a characteristic appearance
and causing severe itching. AIM: To assess the potency of transcutaneous
electrical nerve stimulation (TENS) as an antipruritic line of treatment in
patients with LP. METHODS: We enrolled 30 patients with LP who had a history of
recurrent relapses of confined pruritus forcing them to scratch or rub the
affected area intensively. Patients were treated with TENS three times per week
for 4 weeks. Severity of itching was estimated by visual analogue scale (VAS) and
Dermatology Life Quality Index (DLQI). RESULTS: There was a statistically
significant decline in mean VAS score at weeks 2 and 4 of treatment compared with
baseline (P < 0.05, with 74% of participants having an improvement of > 50%.
Significant improvement in itching intensity also resulted in better quality of
life, as there was also a significant reduction in median DLQI at weeks 2 and 4
of therapy compared with baseline (P < 0.05), with 65% of patients having an
improvement of > 50% in median DLQI score. CONCLUSION: TENS may be an alternative
safe treatment for LP-induced itching.
PMID- 29947142
TI - A classroom intervention to improve executive functions in late primary school
children: Too 'old' for improvements?
AB - BACKGROUND: Given the strong relationship between executive functions and
academic achievement, there has been great interest in improving executive
functions. School-based group interventions targeting executive functions
revealed encouraging results in preschoolers and young school children; however,
there is a paucity of studies in older primary school children (age 10-12). This
is surprising considering that deficits in executive function performance can
often be observed in this age group. AIMS: Therefore, the aim of this study was
to examine whether an innovative customized school-based group intervention could
improve core executive functions (updating, inhibition, and shifting) in the age
group concerned. SAMPLE: In total, 118 ten- to twelve-year-old school children
were recruited from eight participating classes. METHODS: They were randomly
assigned to one of two-six-week conditions of either a cognitive games group
comprising of card and board games training executive functions (experimental
group) or a wait-list control group (regular school lessons). In the cognitive
games group, the class teachers held a 30-min training session twice a week.
ANCOVAs (using pre-test values as covariate) were used to compare executive
function performance between groups. RESULTS: Results revealed that the cognitive
games group improved specific executive functions (updating and shifting)
compared to the control group. These findings indicate that a school-based group
intervention can improve executive functions, even in 'older' primary school
children. CONCLUSION: This study provides empirical evidence for the
effectiveness of a classroom-based cognitive training in older primary school
children and is of practical relevance for educators.
PMID- 29947143
TI - Chronic blepharitis.
PMID- 29947144
TI - Survival benefits of adjuvant radiation in the management of early tongue cancer
with depth of invasion as the indication.
AB - BACKGROUND: With the introduction of new American Joint Committee on Cancer
(AJCC) classifications for head and neck cancers few cases are upgraded from T2
to T3 based only on depth of invasion. The role of adjuvant therapy in this
particular subset of patients is still not defined. METHODS: This is a
retrospective analysis of data from 2009 to 2015, of patients with histopathology
of pT1, T2, and N0. A total of 375 patients were subdivided into 3 groups per the
new AJCC classification depth of invasion <5 mm, 6 to 10 mm, and >10 mm. Survival
analyses of patients receiving adjuvant therapy and those who did not were
compared with specific emphasis on patients who were upstaged from T2 to T3 based
on depth of invasion. RESULTS: Depth of invasion is a poor prognostic factor and
addition of adjuvant therapy based on depth of invasion did not have significant
survival benefits. CONCLUSION: Addition of adjuvant therapy based on depth of
invasion does not influence survival in patients with early carcinoma of the
tongue.
PMID- 29947145
TI - Screening of seized cocaine samples using electrophoresis microchips with
integrated contactless conductivity detection.
AB - This study describes the development of a new analytical method for the
separation and detection of cocaine (COC) and its adulterants, or cutting agents,
using microchip electrophoresis (ME) devices coupled with capacitively coupled
contactless conductivity detection (C4 D). All the experiments were carried out
using a glass commercial ME device containing two pairs of integrated sensing
electrodes. The running buffer composed of 20 mmol/L amino-2-(hydroxymethyl)
propane-1,3-diol and 10 mmol/L 3,4-dimethoxycinnamic acid provided the best
separation conditions for COC and its adulterants with baseline resolution (R >
1.6), separation efficiencies ranging from (2.9 +/- 0.1) to (3.2 +/- 0.2) * 105
plates/m, and estimated LOD values between 40 and 150 MUmol/L. The quantification
of COC was successfully performed in four samples seized by the Brazilian Federal
Police Department and all predicted values agree with values estimated by the
reference method. Some other interfering species were detected in the seized
samples during the screening procedure on ME-C4 D devices. While lidocaine was
detected in sample 3, the presence of levamisole was observed in samples 2 and 4.
However, their concentrations were estimated to be below the LOQ. ME-C4 D devices
have proved to be quite efficient for the identification and quantification of
COC with errors lower than 10% when compared to the data obtained by a reference
method. The approach herein reported offers great potential to be used for on
site COC screening in seized samples.
PMID- 29947146
TI - Cervical left aortic arch with distal tortuosity causing coarctation and
aneurysmal formation in a child.
AB - We present a case of a 10-year-old female with a cervical aortic arch and distal
transverse arch tortuosity causing coarctation and aneurysmal formation and
describe the surgical repair of this rare congenital anomaly.
PMID- 29947147
TI - Longitudinal profile of circulating T follicular helper lymphocytes parallels
anti-HLA sensitization in renal transplant recipients.
AB - Antibody-mediated rejection is responsible for 30%-50% of renal graft failures.
Differentiation of B cells into antibody-producing plasmablasts depends on the
collaboration of follicular helper T cells (Tfh). We analyzed circulating Tfh
(cTfh) in kidney recipients and studied cTfh relationship with anti-HLA antibody
production and graft outcome. cTfh were longitudinally analyzed in a prospective
cohort of patients (n = 206), pre- and posttransplantation. Clinical data, HLA
sensitization, and cTfh function were recorded. Both pretransplant and 6-month
posttransplant cTfh were able to derive IgG-producing plasmablasts. Pretransplant
cTfh was decreased in patients, especially in those who received dialysis.
However, these cells were increased in patients with previous allograft or
transfusions and in HLA-sensitized recipients. After transplantation cTfh
expanded, significantly more in patients who developed de novo anti-HLA
antibodies than in patients who remained unsensitized. Augmented pretransplant
cTfh positively correlated with higher intensity of pretransplant anti-HLA class
I and with de novo anti-HLA class I and anti-HLA class II antibodies.
Consistently, pretransplantation cTfh were higher in patients who experienced
acute rejection (HR = 1.14 [1.04-1.25]). Thus, we show a role for Tfh in anti-HLA
sensitization and rejection. Multicenter studies with additional patient cohorts
are needed to validate these results. Immunosuppressive drugs targeting Tfh could
be useful to improve outcomes.
PMID- 29947148
TI - Maturational trajectories of local and long-range functional connectivity in
autism during face processing.
AB - Autism spectrum disorder (ASD) is characterized neurophysiologically by, among
other things, functional connectivity abnormalities in the brain. Recent evidence
suggests that the nature of these functional connectivity abnormalities might not
be uniform throughout maturation. Comparing between adolescents and young adults
(ages 14-21) with ASD and age- and IQ-matched typically developing (TD)
individuals, we previously documented, using magnetoencephalography (MEG) data,
that local functional connectivity in the fusiform face areas (FFA) and long
range functional connectivity between FFA and three higher order cortical areas
were all reduced in ASD. Given the findings on abnormal maturation trajectories
in ASD, we tested whether these results extend to preadolescent children (ages 7
13). We found that both local and long-range functional connectivity were in fact
normal in this younger age group in ASD. Combining the two age groups, we found
that local and long-range functional connectivity measures were positively
correlated with age in TD, but negatively correlated with age in ASD. Last, we
showed that local functional connectivity was the primary feature in predicting
age in ASD group, but not in the TD group. Furthermore, local functional
connectivity was only correlated with ASD severity in the older group. These
results suggest that the direction of maturation of functional connectivity for
processing of faces from childhood to young adulthood is itself abnormal in ASD,
and that during the processing of faces, these trajectory abnormalities are more
pronounced for local functional connectivity measures than they are for long
range functional connectivity measures.
PMID- 29947149
TI - Enzymatic Thioamide Formation in a Bacterial Antimetabolite Pathway.
AB - 6-Thioguanine (6TG) is a DNA-targeting therapeutic used in the treatment of
various cancers. While 6TG was rationally designed as a proof of concept for
antimetabolite therapy, it is also a rare thioamide-bearing bacterial natural
product and critical virulence factor of Erwinia amylovorans, plant pathogens
that cause fire blight. Through gene expression, biochemical assays, and
mutational analyses, we identified a specialized bipartite enzyme system,
consisting of an ATP-dependent sulfur transferase (YcfA) and a sulfur-mobilizing
enzyme (YcfC), that is responsible for the peculiar oxygen-by-sulfur substitution
found in the biosynthesis of 6TG. Mechanistic and phylogenetic studies revealed
that YcfA-mediated 6TG biosynthesis evolved from ancient tRNA modifications that
support translational fidelity. The successful in vitro reconstitution of 6TG
thioamidation showed that YcfA employs a specialized sulfur shuttle that markedly
differs from universal RNA-related systems. This study sheds light on
underexplored enzymatic C-S bond formation in natural product biosynthesis.
PMID- 29947151
TI - The Impact of the Complexing Cation on the Sensitivity of the Collisional-Induced
Dissociation Spectra to Fatty Acid Position for a Set of YXY/YYX-type
Triglycerides.
AB - RATIONAL: The development of an automated platform for the positional analysis of
triglycerides based on electrospray tandem mass spectrometry continues to be
pursued. This work compares the positional sensitivities of the collisional
induced dissociation spectra for a representative set of YXY/YYX triglycerides
using ammonium, silver, sodium and lithium as complexing agents. METHODS: A set
of triglycerides were synthesized and analyzed by electrospray tandem mass
spectrometry using an ion trap mass spectrometer. Using different salt additives,
the product ion spectra of the corresponding parent ions for twelve systems of
the form YXY/YYX, where Y and X represent C16:0 , C18:1(c-9), C18:2(cc-9,12) and
C20:4(cccc-5,8,11,14) , were collected. The data was used to prepare two-point
calibration plots for each of the twelve positional isomer systems using each of
the four complexing agents. RESULTS: The positional sensitivities for all twelve
positional isomer systems were robust for both the sodium and lithium TAG
adducts. The CID data for both the sodium and lithium TAG adducts are much less
sensitive to the degree of unsaturation and double bond position of the fatty
acids constituents than the CID data for the ammonium adducts. CONCLUSION: Using
sodium or lithium TAG adducts may be advantageous for the development of an
accurate predictive model for performing positional analysis of complex TAG
mixtures based on electrospray tandem mass spectrometry. Ammonium adducts are
likely complicated by the ability of the ammonium ion to provide extra stability
to some parent ions through hydrogen bond-like interactions.
PMID- 29947150
TI - Hospital outcomes of older people with cognitive impairment: An integrative
review.
AB - OBJECTIVES: To summarise existing knowledge of outcomes of older hospital
patients with cognitive impairment, including the type and frequency of outcomes
reported, and the additional risk experienced by this patient group. METHODS:
Integrative literature review. Health care literature databases, reports, and
policy documents on key websites were systematically searched. Papers describing
the outcomes of older people with cognitive impairment during hospitalisation and
at discharge were analysed and summarised using integrative methods. RESULTS: One
hundred four articles were included. A range of outcomes were identified,
including those occurring during hospitalisation and at discharge. Older people
with a dementia diagnosis were at higher risk from death in hospital, nursing
home admission, long lengths of stay, as well as intermediate outcomes such as
delirium, falls, dehydration, reduction in nutritional status, decline in
physical and cognitive function, and new infections in hospital. Fewer studies
examined the relationship of all-cause cognitive impairment with outcomes.
Patient and carer experiences of hospital admission were often poor. Few studies
collected data relating to hospital environment, eg, ward type or staffing
levels, and acuity of illness was rarely described. CONCLUSIONS: Older people
with cognitive impairment have a higher risk of a variety of negative outcomes in
hospital. Prevalent intermediate outcomes suggest that changes in care processes
are required to ensure maintenance of fundamental care provision and greater
attention to patient safety in this vulnerable group. More research is required
to understand the most appropriate ways of doing this and how changes in these
care processes are best implemented to improve hospital outcomes.
PMID- 29947152
TI - T cell receptor repertoire profiling predicts the prognosis of HBV-associated
hepatocellular carcinoma.
AB - Tumor-infiltrating T cell repertoire has been demonstrated to be closely
associated with anti-tumor immune response. However, the relationship between T
cell repertoire in tumor tissue and prognosis has never been reported in
Hepatocellular carcinoma (HCC). We performed the high-throughput T cell receptor
(TCR) sequencing to systematically characterize the infiltrating T cell
repertoires of tumor and matched adjacent normal tissues from 23 HBV-associated
HCC patients. Significant differences on usage frequencies of some Vbeta, Jbeta,
and Vbeta-Jbeta paired genes have been found between the 2 groups of tissue
samples, but no significant difference of TCR repertoire diversity could be
found. Interestingly, the similarity of TCR repertoires between paired samples or
the TNM stage alone could not be helpful to evaluate the prognosis of patients
very well, but their combination could serve as an efficient prognostic indicator
that the patients with early stage and high similarity showed a better prognosis.
This is the first attempt to assess the potential value of TCR repertoire in HCC
prognosis, and our findings could serve as a complement for the characterization
of TCR repertoire in HCC.
PMID- 29947153
TI - Cytocompatible Fabrication of Yeast Cells/Fabrics Composite Sheet for Bioethanol
Production.
AB - Entrapment of living cells into a polymer network has significant potential in
various fields such as biomass conversion and tissue engineering. A crucial
challenge for this strategy is to provide a mild enough condition to preserve
cell viability. Here, a facile and cytocompatible method to entrap living yeast
cells into a poly(ethylene glycol) (PEG) network grafting from polypropylene
nonwoven fabrics via visible-light-induced surface living graft crosslinking
polymerization is reported. Due to the mild reaction conditions and excellent
biocompatibility of PEG, the immobilized yeast cells could maintain their
viability and proliferate well. The obtained composite sheet has excellent long
term stability and shows no significant efficiency loss after 25 cycles of
repeated batch bioethanol fermentation. The immobilized yeast cells exhibit 18.0%
higher bioethanol fermentation efficiency than free cells. This strategy for
immobilization of living cells with high viability has significant potential
application.
PMID- 29947154
TI - Live donor liver transplantation with older donors: Increased long-term graft
loss due to HCV recurrence.
AB - Using our prospectively collected database all adult hepatitis C virus (HCV)
positive patients receiving an adult-to-adult LDLT between October 2000 and May
2014 were identified. Outcome of LDLT with grafts from younger (<50 years=128) vs
older donors (>=50 years=31) was compared. Post-transplant graft function,
postoperative complications and incidence of HCV recurrence were evaluated. Long
term graft and patient survival was calculated. No difference in graft function
was observed between younger and older grafts. Overall complications were similar
between both groups. The severity of complications determined by the Dindo
Clavien score was similar. Graft loss from HCV recurrence was significantly less
frequent in younger grafts (18% vs 62%, P = 0.001). Young vs older livers had a
trend toward improved 1-, 5-, and 10-year graft survival (89% vs 87%, 77% vs 69%,
70% vs 55%, P = 0.096), while patient survival was comparable between both groups
(91% vs 90%, 78% vs 69%, 71% vs 60%, P = 0.25). In conclusion, LDLT with older vs
younger grafts are more frequently associated with long-term graft loss due to
HCV recurrence. Differences in graft survival might be more prominent with
prolonged (>=5-year) follow-up. Living donor-recipient matching is particularly
important for younger HCV-positive recipients.
PMID- 29947155
TI - Clinical validation of the nursing diagnosis of impaired memory in patients with
a stroke.
PMID- 29947156
TI - Green tea as a safe alternative approach for nonalcoholic fatty liver treatment:
A systematic review and meta-analysis of clinical trials.
AB - This study aimed to evaluate the efficacy of green tea supplementation on
nonalcoholic fatty liver disease treatment. Electronic databases, including
PubMed, Scopus, Web of Science, and Google Scholar, were systematically searched
up to October 30, 2017, to identify eligible trials based on the inclusion
criteria. The effect size was presented as mean difference with 95% confidence
intervals (CI). The meta-analysis of data from four studies indicated significant
effects of green tea supplementation in altering alanine aminotransferases (
12.81 U/L; 95% CI: -18.17 to -7.45) and aspartate aminotransferases (-10.91 U/L;
95% CI: -19.66 to -2.17) blood concentrations. Likewise, a favorable effect of
green tea administration was observed on body mass index (-2.08 kg/cm2 ; 95% CI:
2.81 to -1.36), triacylglycerol (-31.87 mg/dl; 95% CI: -40.62 to -23.12), total
cholesterol (-27.57 mg/dl; 95% CI: -36.17 to -18.98), and low-density lipoprotein
cholesterol (-14.15 mg/dl; 95% CI: -23.69 to -4.60), whereas no significant
effect was detected on high-density lipoprotein cholesterol concentrations (7.41
mg/dl; 95% CI: -1.49 to 16.30) and homeostasis model assessment of insulin
resistance (-4.06; 95% CI: -10.22 to 2.09). This systematic review and meta
analysis of available trials suggests that there are potential benefits of green
tea supplementation on nonalcoholic fatty liver disease.
PMID- 29947157
TI - Initiating discussions about weight in a non-weight-specific setting: What can we
learn about the interactional consequences of different communication practices
from an examination of clinical consultations?
AB - OBJECTIVES: Effective clinical communication is fundamental to tackling
overweight and obesity. However, little is known about how weight is discussed in
non-weight-specific settings where the primary purpose of the interaction
concerns clinical matters apparently unrelated to weight. This study explores how
mental health clinicians initiate discussions about a patient's possible weight
problem in the non-weight-specific setting of a UK NHS Gender Identity Clinic
(GIC), where weight is topicalized during discussions about the risks of
treatment. DESIGN: A conversation analytic study. METHODS: A total of 194
recordings of routine clinician-patient consultations were collected from the
GIC. Weight talk was initiated by four clinicians in 43 consultations. Twenty-one
instances contained reference to a possible weight problem. Transcripts were
analysed using conversation analysis. RESULTS: Clinicians used three
communication practices to initiate discussion of a possible weight problem with
patients: (1) announcing that patients are overweight; (2) asking patients
whether they are overweight; and (3) deducing that patients are overweight or
obese via a body mass index (BMI) calculation. Announcing that patients are
overweight is the least aligning practice that denies patient's agency and
grammatically constrains them to agree with a negative label. Asking patients
whether they are overweight treats them as having limited agency and generates
comparatively aligning, but occasionally resistant, responses. Jointly deducing
that patients are overweight or obese via a BMI calculation is the most aligning
practice, which deflects responsibility for labelling the patient onto an
objective instrument. CONCLUSIONS: Small differences in the wording of turns that
initiate discussions about a possible weight problem can have significant
consequences for interactional alignment. Clinicians from different specialities
may benefit from considering the interactional consequences of different
practices for initiating discussions about weight during the kinds of real-life
discussions considered here. Statement of contribution What is already known on
this subject? There is a correlation between clinical communication about weight
and patient weight loss. Clinicians from all specialties are encouraged to
discuss diet and exercise with patients, but communication about weight remains
problematic. Health psychologists have identified an urgent need for
communication training to raise sensitive topics like weight without damaging the
doctor-patient relationship. What does this study add? Clinicians in a non-weight
specific setting use three communication practices to introduce the possibility
that a patient's weight may be a problem. These practices have varying
consequences for the interaction and doctor-patient relationship. Conversation
analytic findings may be useful in training clinicians how to initiate
discussions about weight with patients.
PMID- 29947158
TI - Correlation between flow cytometry and molecular findings in autosomal recessive
chronic granulomatous disease: A cohort study from Oman.
AB - BACKGROUND: Chronic granulomatous disease (CGD) is an X-linked (XL) or autosomal
recessive (AR) primary immunodeficiency disease. Respiratory burst assessment by
flow cytometry is a rapid test of granulocyte stimulation, and results predict
the underlying genotype. This study aims to describe the immune-phenotypic
profile of patients with CGD diagnosed in our center and correlate that with
underlying genetic mutations. METHODS: Immuno-phenotypic and genetic data on all
patients with CGD diagnosed at Sultan Qaboos University Hospital (SQUH) were
reviewed. RESULTS: A total of 32 patients were diagnosed with CGD using molecular
studies. Genetically confirmed individuals included 1 patient with XL-CGD (a
large deletion involving the CYBB and XK genes resulting in a McLeod phenotype),
27 patients with AR-CGD with a c.579G>A (p.Trp193X) mutation at the NCF1 gene,
and 4 patients with AR-CGD with a c.784G>A (p.Gly262Ser) mutation at the NCF1
gene. Flow cytometry and molecular results were available for comparison in 26
patients with AR-CGD. The patients with AR-CGD had a range of flow cytometry
generated fluorescent patterns as follows: reduced neutrophil stimulation with a
sharp peak (12/26), reduced neutrophil stimulation with a broad peak (11/26), and
a complete lack of neutrophil stimulation (3/26). No consistent flow cytometry
generated fluorescent pattern was observed in either of the 2 AR mutations
identified in our patients. CONCLUSION: Flow cytometry is a robust test of CGD
diagnosis. However, results should be interpreted with caution when predicting
the underlying probable genotype, and results need to be complemented with
definitive molecular studies.
PMID- 29947159
TI - Prevention of maternal-fetal transmission of CMV by hyperimmunoglobulin (HIG)
administered after a primary maternal CMV infectionin early gestation.
AB - OBJECTIVE: To examine the efficacy of biweekly hyperimmunoglobulin (HIG)
administration to women with first trimester CMV infection for preventing
maternal-fetal transmission of CMV. METHODS: Subjects were 40 pregnant women with
a primary CMV infection with a median gestational age at diagnosis of 9.6 weeks
with a range of 5.1 to 14.3 weeks' gestation. On average, HIG administration
started at 11.1 weeks and continued until 16.6 weeks' gestation. Within this
interval, HIG was administered between 2 and 6 times. While CMV IgG monitoring
showed periodic fluctuations during biweekly HIG administration cycles, high CMV
IgG avidity indices remained stable over the whole treatment period. The results
were compared with a historic cohort with first trimester CMV infection without
treatment that also had an amniocentesis at about 20 weeks RESULTS: Each subject
had amniocentesis performed. Maternal-fetal transmission before amniocentesis
occurred in only one of the 40 cases (2.5%, [95% CI:0 - 13.2%]). At delivery, two
additional subjects had late gestation transmission. Considering all three cases
with maternal-fetal transmission, the transmission rate was 7.5% of 40 cases,
[95% CI: 1,6 - 20.4%]). All infected neonates were asymptomatic at birth. Matched
historical controls were 108 pregnancies with 38 transmissions (35.2%, [95% CI:
26.2 - 45.0%]), which was significantly higher than in the HIG administration
group. CONCLUSION: After a primary maternal CMV infection in the first trimester,
HIG administration prevents maternal-fetal transmission up to 20 weeks of
gestation. This article is protected by copyright. All rights reserved.
PMID- 29947160
TI - Experiences of a transdiagnostic group, the Take Control Course, for clients with
common mental health problems: A qualitative study.
AB - OBJECTIVES: Despite the promising effectiveness findings for transdiagnostic
groups, studies have not explored clients' experiences. There is a risk that
clients could perceive that the content of transdiagnostic groups is not
sufficiently tailored to their specific problems. Our aims were to examine
whether a brief transdiagnostic group, the Take Control Course (TCC), was
acceptable to participants and to explore participants' perceptions of
psychological change. METHODS: Qualitative data were collected via 12
semistructured, in-depth interviews. Data collection and thematic analysis were
concurrent and iterative. RESULTS: Three superordinate themes were identified:
"Style and format," "Control and flexibility," and "Change." The flexible group
format was appreciated, as participants felt able to engage at their own pace and
adapt relevant aspects. Greater clarity regarding what was within participants'
control reduced distress and enabled effective pursuit of valued goals.
Participants described significant (predominantly gradual) changes, including
substantial improvements within relationships. CONCLUSIONS: The transdiagnostic
format did not prevent participants experiencing the TCC as individually
relevant. The flexibility and consistent theoretical framework seemed to
contribute to this. The results indicated that greater consideration of control
and mindfulness allowed greater cognitive flexibility, an ability to reprioritize
and let go of unhelpful habits, which better enabled participants to meet their
goals. Implications for group therapy include (a) clearly explaining the format
of such groups to clients and (b) providing flexibility in the way the group is
delivered where possible. Additional qualitative studies of transdiagnostic
groups are required to establish if themes generalize to other transdiagnostic
groups.
PMID- 29947161
TI - How reliable is fetal occiput and spine position assessment prior to induction of
labor?
AB - OBJECTIVES: To assess the reliability of fetal occiput and spine position
determination in nulliparous women prior to the induction of labor (IOL). We
aimed also to evaluate the value of identifying the fetal occiput and spine
positions prior to IOL in the prediction of labor outcome. METHODS: A series of
136 nulliparous were recruited immediately after the decision of induction of
labor. Transabdominal ultrasound was performed to determine fetal head and spine
position. After at least one hour, and prior to induction of labor, fetal occiput
and spine positions were reassessed. Fetal occiput and spine position were then
compared between women who underwent vaginal delivery (VD) and those who
delivered by Cesarean section (CS). RESULTS: Fetal occiput position was anterior
in 55 (40.4%) and in 62 (45.6%), transverse in 52 (38.2%) and in 49 (36.0%), and
posterior in 29 (21.3%) and in 25 (18.4%) of women on the first and second
assessment, respectively. On the other hand, spine position was anterior in 58
(42.6%) and in 52 (38.2%), transverse in 42 (30.9%) and in 50 (36.8%), and
posterior in 34 (25%) and in 36 (26.5%) of women on the first and second
assessment, respectively. Regarding fetal occiput position, discordance between
the first and second assessment was identified in 34 (25%), whereas discordance
of fetal spine position was observed in 40 (29.4%) women. Women undergoing CS had
a comparable incidence of occiput posterior in comparison with the VD group (19
(18.8%) vs. 6 (17.1%); P=0.826) and of fetal posterior spine position (27 (26.7%)
vs. 7(20%); P=0.428). Lastly, women with OP position had a longer induction-to
delivery duration in comparison with those with non-OP position. CONCLUSIONS:
Fetal occiput and spine positions are dynamic in a considerable proportion of
women undergoing induction of labor. Furthermore, both assessments do not seem to
correlate with the mode of delivery. Occiput and spine position assessment prior
to induction of labor are unlikely to be clinically useful in women undergoing
IOL. This article is protected by copyright. All rights reserved.
PMID- 29947162
TI - Cataract surgery in Hauora Tairawhiti and need for improving access for Maori.
PMID- 29947163
TI - Kidney transplant from uncontrolled donation after circulatory death donors
maintained by nECMO has long-term outcomes comparable to standard criteria
donation after brain death.
AB - Uncontrolled donation after circulatory death (uDCD) increases organ availability
for kidney transplant (KT) with short-term outcomes similar to those obtained
from donation after brain death (DBD) donors. However, heterogeneous results in
the long term have been reported. We compared 10-year outcomes between 237 KT
recipients from uDCD donors maintained by normothermic extracorporeal membrane
oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD
donors during the same period at our institution. We further analyzed risk
factors for death-censored graft survival in the uDCD group. Delayed graft
function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01),
although glomerular filtration rates at the end of follow-up were similar in the
2 groups. uDCD and DBD groups had similar rates for 10-year death-censored graft
(82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454).
Donor age >50 years was associated with graft loss in the uDCD group (hazard
ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant
effect. uDCD KT under nECMO support resulted in similar graft function and long
term outcomes compared with KT from standard criteria DBD donors. Increased donor
age could negatively affect graft survival after uDCD donation.
PMID- 29947165
TI - Qualitative insights into the experience of pain in older Australian women with
arthritis.
AB - OBJECTIVE: To explore qualitative insights into the pain experience of older
women with quantitatively derived pain profiles. METHODS: The sequential mixed
methods design involved applying quantitative pain profiles, derived from an
earlier latent class analysis, to qualitative comments by a sample of older
Australian women with arthritis. Data from a substudy of the Australian
Longitudinal Study on Women's Health, mid-aged cohort, born 1946-1951, were used.
Inductive content analysis was conducted to explore qualitative insights into the
experience of pain. RESULTS: The average age of women was 64.6 years (+/-1.4).
Within each derived pain profile, themes generated from the qualitative comments
of women were concordant with the profile descriptors: 'I manage my pain' for the
uni-dimensional, mild pain profile (comments from 56 women); 'I live with pain
every day' and 'I rely on medication regularly' for the moderate multidimensional
pain profile (comments from 39 women); and 'multiple pains', 'I suffer with pain'
and 'I am unable and adjust' for the severe multidimensional pain profile
(comments from 31 women). CONCLUSION: Women with different pain profiles used
different language and strategies in managing their pain experience, information
which can guide clinicians to provide more tailored support for self-management
and care of arthritis pain.
PMID- 29947164
TI - Exploring 3-hinge gyral folding patterns among HCP Q3 868 human subjects.
AB - Comparison and integration of neuroimaging data from different brains and
populations are fundamental in neuroscience. Over the past decades, the
neuroimaging field has largely depended on image registration to compare and
integrate neuroimaging data from individuals in a common reference space, with a
basic assumption that the brains are similar. However, the intrinsic
neuroanatomical complexity and huge interindividual cortical folding variation
remain underexplored. Here we focus on a specific cortical convolution pattern,
termed 3-hinge gyral folding, which is the conjunction of gyri from multiple
orientations and has unique and consistent anatomically, structurally, and
functionally connective patterns across subjects. By developing a novel shape
descriptor and a two-stage clustering pipeline, we devise an automatic method to
identify 3-hinges in the Human Connectome Project Q3 868 human brains, and
further parameterize the complexity of such a pattern and quantify its regularity
and variation in terms of 3-hinge number, position, and morphology. Our results
not only exhibit the huge interindividual variations, but also reveal regular
relationship between gyral hinges and other factors, such as their locations and
cortical morphologies. It is found that "line-shape" cortices have relatively
more consistent 3-hinge shape pattern distributions, and certain types of 3-hinge
patterns favor particular cortical morphologies. In addition, more 3-hinges are
found on "line-shape" cortices while their numbers vary more across subjects than
those on "non-line-shape" cortices. This study adds new insights into a better
understanding of the regularity and variability of human brain anatomy, and their
functional aspects.
PMID- 29947167
TI - A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has
anything changed in the past 20 years?
AB - BACKGROUND: Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon yet
potentially lethal fungal infection. Although most cases originate from
developing countries, an ageing population and increased prevalence of chronic
illness may mean some clinicians practicing in developed countries will encounter
ROCM cases in their careers. Yohai et al published a systematic review of 145
case reports from 1970 to 1993 assessing prognostic factors for patients
presenting with ROCM. We present an updated review of the literature and assess
whether survival outcomes have changed in the two decades since that seminal
paper. SEARCH STRATEGY: An extensive Medline literature search was performed for
case reports published between 1994 and 2015. RESULTS: In total, 210 published
cases were identified from the literature review, of which 175 patients from 140
papers were included in this review. Fifty-five were female, with an overall mean
age of 43 years. Overall survival rate was 59.5%, which was not significantly
better than the previous series reported (60%) reported by Yohai et al. Survival
rates in patients with chronic renal disease had improved, from 19% to 52%, and
in patients with leukaemia (from 13% to 50%). Facial necrosis and hemiplegia
remained poor prognostic indicators (33% and 39% survival rates, respectively).
Early commencement of medical treatment related to better survival outcomes (61%
if commenced within first 12 days of presentation, compared to 33% if after 13
days). Timing of surgery had less of an effect on overall survival. However, in
28 cases that did not receive any surgical treatment, survival was only 21%.
CONCLUSIONS: Although overall survival rates have not improved, survival in
patients with renal disease were better, potentially due to the introduction of
liposomal amphotericin B which is less nephrotoxic. Prompt recognition of ROCM,
reversal of predisposing co-morbidities and aggressive medical treatment remain
the cornerstone of managing this highly aggressive disease.
PMID- 29947166
TI - Maternal obesity stimulates lipotoxicity and up-regulates inflammatory signaling
pathways in the full-term swine placenta.
AB - This study aimed to investigate the effects of back-fat thickness (BF), at mating
of sows, on placental lipotoxicity, oxidative stress, and inflammation. We
performed iTRAQ labeling-based proteomic analysis on term placentas obtained by
vaginal delivery from BFI (15-20 mm, control) and BFII (21-27 mm, obese) sows
formed according to BF at mating. Proteomic analysis revealed 413 proteins to be
significantly different in placenta from BFII sows by >=1.2-fold. Gene ontology
(GO) analysis identified proteins related to lipid metabolism and inflammatory
response to be altered in placenta from obese sows. Indicative of a lipotoxic
placental environment, increased placental lipid, and up-regulated mRNA
expression of lipogenic genes, including ADRP (p = .06), PPARD, FASN, ACACA,
DGAT1, and LIPIN3, were associated with decreased AMPK and increased activation
of WNT signaling in placenta from BFII group (p < .05). Furthermore, we observed
a 18% decrease in total antioxidant capacity (TAC), increased mRNA content of pro
inflammatory cytokines IL-6, IL-18, and TNF-alpha, and increased activation of
inflammatory NF-kappaB and JNK signaling in placenta from BFII sows that was
significantly associated with macrophage accumulation (p < .05). These findings
suggest that maternal obesity aggravates a lipotoxic environment in pig term
placenta that may be associated with placental dysfunction and impaired fetal
growth.
PMID- 29947168
TI - The risk of long-term bowel dysfunction after resection for sigmoid
adenocarcinoma: a cross-sectional survey comparing complete mesocolic excision
with conventional surgery.
AB - AIM: To investigate whether complete mesocolic excision (CME) might carry a
higher risk of bowel dysfunction and subsequent reduction in quality of life
compared with conventional resection. METHOD: A cross-sectional questionnaire
study based on data from a national survey regarding long-term bowel function and
a population-based cohort study comparing CME (study group) with conventional
resection (control group). A total of 622 patients undergoing elective resection
for Stage I-III sigmoid adenocarcinoma at four university colorectal centres
between June 2008 and December 2014 were eligible to receive the questionnaire in
mid-November 2015. Primary outcomes were four or more bowel movements daily,
nocturnal bowel movements, unproductive call to stool, obstructive sensation and
impact of bowel function on quality of life (QOL). RESULTS: One hundred and
twenty-seven (69.0%) and 289 (66.0%) patients in the study and control groups,
respectively, responded to the questionnaire after medians of 4.41 [interquartile
range (IQR) 2.50, 5.83] and 4.57 (IQR 3.15, 5.82) years, respectively (P =
0.048). CME was not associated with: increased risk of four or more bowel
movements daily [adjusted OR 1.14 (95% CI 0.59-2.14; P = 0.68)], nocturnal bowel
movements [adjusted OR 1.31 (0.66-2.53; P = 0.43)], unproductive call to stool
[adjusted OR 0.99 (0.54-1.77; P = 0.97)] or obstructive sensation [adjusted OR
1.01 (0.56-1.78; P = 0.96)]. While one in five patients in both groups had
moderate to severe impact of bowel function on QOL, there was no association with
CME. CONCLUSION: For patients with sigmoid cancer, CME is associated with neither
higher risk of bowel dysfunction nor impaired QOL.
PMID- 29947169
TI - Meta-analyses and blood pressure goals.
PMID- 29947170
TI - Effectiveness of temozolomide combined with whole brain radiotherapy for non
small cell lung cancer brain metastases.
AB - BACKGROUND: We performed a retrospective analysis to compare the efficacy of
whole brain radiotherapy (WBRT) combined with temozolomide (TMZ) versus WBRT
alone as first-line treatment for brain metastases (BM). METHODS: Seventy-eight
non-small cell lung cancer patients with BM were observed, including 45 patients
who received WBRT plus TMZ (TMZ + WBRT) and 33 patients who received WBRT alone
(WBRT). The primary outcome was overall survival (OS). Secondary outcomes
included progression-free survival (PFS), objective response rate (ORR), and
adverse events. RESULTS: The TMZ + WBRT arm achieved significant improvement in
ORR (P = 0.0108) compared to the WBRT arm. PFS in the TMZ + WBRT arm was
significantly longer than in the RT arm (6.0 vs. 3.5 months; P = 0.038). OS was
not significantly different between the two arms. Although increased adverse
reactions were experienced in the TMZ + WBRT arm, patients were tolerant of the
side effects. Statistically significant differences in neurocognitive function
and quality of life were observed between the arms at six months. CONCLUSION:
Concomitant TMZ + WBRT compared to WBRT alone significantly increases ORR and
median PFS in patients with BM, but no remarkable difference in median OS was
found. Adding TMZ to the treatment strategy could prevent neurocognitive function
and quality of life from deteriorating. Although the addition of TMZ increases
the incidence of adverse effects, no significant difference was observed. Thus,
TMZ is safe and effective.
PMID- 29947171
TI - Recent Updates on the Diagnosis and Management of Cushing's Syndrome.
AB - Cushing's syndrome, a potentially lethal disorder characterized by endogenous
hypercortisolism, may be difficult to recognize, especially when it is mild and
the presenting features are common in the general population. However, there is a
need to identify the condition at an early stage, as it tends to progress,
accruing additional morbidity and increasing mortality rates. Once a clinical
suspicion is raised, screening tests involve timed measurement of urine, serum or
salivary cortisol at baseline or after administration of dexamethasone, 1 mg.
Each test has caveats, so that the choice of tests must be individualized for
each patient. Once the diagnosis is established, and the cause is determined,
surgical resection of abnormal tumor/tissue is the optimal treatment. When this
cannot be achieved, medical treatment (or bilateral adrenalectomy) must be used
to normalize cortisol production. Recent updates in screening for and treating
Cushing's syndrome are reviewed here.
PMID- 29947173
TI - Genetic Polymorphism Predisposing to Differentiated Thyroid Cancer: A Review of
Major Findings of the Genome-Wide Association Studies.
AB - Thyroid cancer has one of the highest hereditary component among human
malignancies as seen in medical epidemiology investigations, suggesting the
potential meaningfulness of genetic studies. Here we review researches into
genetic variations that influence the chance of developing non-familial
differentiated thyroid cancer (DTC), focusing on the major findings of the genome
wide association studies (GWASs) of common single-nucleotide polymorphisms
(SNPs). To date, eight GWAS have been performed, and the association of a number
of SNPs have been reproduced in dozens of replication investigations across
different ethnicities, including Korea and Japan. Despite the cumulative effect
of the strongest SNPs demonstrates gradual increase in the risk for cancer and
their association signals are statistically quite significant, the overall
prediction ability for DTC appears to be very limited. Thus, genotyping of common
SNPs only would be insufficient for evidence-based counseling in clinical setting
at present. Further studies to include less significant and rare SNPs, non-SNP
genetic information, gene-gene interactions, ethnicity, non-genetic and
environmental factors, and development of more advanced computational algorithms
are warranted to approach to personalized disease risk prediction and
prognostication.
PMID- 29947172
TI - Latent Autoimmune Diabetes in Adults: Current Status and New Horizons.
AB - Autoimmune diabetes is a heterogeneous disease which can arise at any age.
Subjects with adult-onset autoimmune diabetes who do not necessitate insulin
therapy for at least 6 months after diagnosis are demarcated as having latent
autoimmune diabetes in adults (LADA). This condition is more heterogeneous than
young-onset autoimmune diabetes and shares clinical and metabolic characteristics
with both type 2 and type 1 diabetes. Patients with LADA are considered by having
highly variable beta-cell destruction, different degrees of insulin resistance
and heterogeneous titre and pattern of islet autoantibody, suggesting different
pathophysiological pathways partially explaining the heterogeneous phenotypes of
LADA. To date the heterogeneity of LADA does not allow to establish a priori
treatment algorithm and no specific guidelines for LADA therapy are available.
These subjects are mostly treated as affected by type 2 diabetes, a factor that
might lead to the progression to insulin-dependency quickly. A personalised
medicine approach is necessary to attain optimal metabolic control and preserve
beta-cell function to decrease the risk of long-term diabetes complications.
Recent data concerning the use of oral antidiabetic agents as dipeptidyl
peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up
and-coming results in term of protect C-peptide levels and improving glycaemic
control. This review summarises current knowledge on LADA, emphasising
controversies regarding its pathophysiology and clinical features. Moreover, we
discuss data available about novel therapeutic approaches that can be considered
for prevention of beta-cell loss in LADA.
PMID- 29947174
TI - Genome-Wide Association Studies of Autoimmune Thyroid Diseases, Thyroid Function,
and Thyroid Cancer.
AB - Thyroid diseases, including autoimmune thyroid diseases and thyroid cancer, are
known to have high heritability. Family and twin studies have indicated that
genetics plays a major role in the development of thyroid diseases. Thyroid
function, represented by thyroid stimulating hormone (TSH) and free thyroxine
(T4), is also known to be partly genetically determined. Before the era of genome
wide association studies (GWAS), the ability to identify genes responsible for
susceptibility to thyroid disease was limited. Over the past decade, GWAS have
been used to identify genes involved in many complex diseases, including various
phenotypes of the thyroid gland. In GWAS of autoimmune thyroid diseases, many
susceptibility loci associated with autoimmunity (human leukocyte antigen [HLA],
protein tyrosine phosphatase, non-receptor type 22 [PTPN22], cytotoxic T
lymphocyte associated protein 4 [CTLA4], and interleukin 2 receptor subunit alpha
[IL2RA]) or thyroid-specific genes (thyroid stimulating hormone receptor [TSHR]
and forkhead box E1 [FOXE1]) have been identified. Regarding thyroid function,
many susceptibility loci for levels of TSH and free T4 have been identified
through genome-wide analyses. In GWAS of differentiated thyroid cancer,
associations at FOXE1, MAP3K12 binding inhibitory protein 1 (MBIP)-NK2 homeobox 1
(NKX2-1), disrupted in renal carcinoma 3 (DIRC3), neuregulin 1 (NRG1), and
pecanex-like 2 (PCNXL2) have been commonly identified in people of European and
Korean ancestry, and many other susceptibility loci have been found in specific
populations. Through GWAS of various thyroid-related phenotypes, many
susceptibility loci have been found, providing insights into the pathogenesis of
thyroid diseases and disease co-clustering within families and individuals.
PMID- 29947176
TI - Triennial Report of Endocrinology and Metabolism, 2015 to 2017.
PMID- 29947175
TI - Management of Low-Risk Papillary Thyroid Cancer.
AB - The incidence of thyroid cancer has increased, mainly due to the incidental
finding of low-risk papillary thyroid cancers (PTC). These malignancies grow
slowly, and are unlikely to cause morbidity and mortality. New understanding
about the prognosis of tumor features has led to reclassification of many tumors
within the low-risk thyroid category, and to the development of a new one "very
low-risk tumors." Alternative less aggressive approaches to therapy are now
available including active surveillance and minimally invasive interventions. In
this narrative review, we have summarized the available evidence for the
management of low-risk PTC.
PMID- 29947177
TI - Parathyroid Hormone-Related Protein in the Hand or Out of Hand?
PMID- 29947178
TI - Procalcitonin as Marker of Recurrent Medullary Thyroid Carcinoma: A Systematic
Review and Meta-Analysis.
AB - BACKGROUND: Calcitonin measurement is pivotal in the management of medullary
thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other
potential markers have been proposed, and procalcitonin (ProCT) has been reported
as promising. The present study was undertaken to summarize the published data
and provide more robust estimates on the reliability of ProCT as marker in the
management of patients with MTC. METHODS: The systematic review was conducted
according to the Preferred Reporting Items for Systematic Reviews and Meta
Analyses (PRISMA) guidelines. The sources comprised studies published through May
2018. Journal Articles that reported series of MTC patients undergone ProCT
during postoperative follow-up were searched. A random-effects model was used for
statistical pooling of the data. The I2 index was used to quantify the
consistency among the studies. The Egger test evaluated the possible presence of
significant publication bias. Quality assessment of the studies was performed
according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).
RESULTS: According to inclusion and exclusion criteria five papers, reporting 296
MTC patients undergone ProCT evaluation, were finally selected. The number of MTC
with recurrence was 140. The pooled sensitivity of ProCT in detecting recurrence
was 96% (95% confidence interval [CI], 92% to 99%), with neither heterogeneity
(I2=0%) nor publication bias (Egger test, 3.16; P=0.99). The pooled specificity
was 96% (95% CI, 87% to 100%) with mild heterogeneity (I2=66.6%), while Egger
test was not calculable. CONCLUSION: The present meta-analysis provides evidence
that ProCT is reliable to manage MTC patients during their postoperative follow
up.
PMID- 29947179
TI - Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with
Unclassical Pseudopseudohypoparathyroidism.
AB - BACKGROUND: Autosomal-dominant brachydactyly type E is a congenital abnormality
characterized by small hands and feet, which is a consequence of shortened
metacarpals and metatarsals. We recently encountered a young gentleman exhibiting
shortening of 4th and 5th fingers and toes. Initially, we suspected him having
pseudopseudohypoparathyroidism (PPHP) because of normal biochemical parameters,
including electrolyte, Ca, P, and parathyroid hormone (PTH) levels; however, his
mother and maternal grandmother had the same conditions in their hands and feet.
Furthermore, his mother showed normal biochemical parameters. To the best of our
knowledge, PPHP is inherited via a mutated paternal allele, owing to the paternal
imprinting of GNAS (guanine nucleotide binding protein, alpha stimulating) in the
renal proximal tubule. Therefore, we decided to further analyze the genetic
background in this family. METHODS: Whole exome sequencing was performed using
genomic DNA from the affected mother, son, and the unaffected father as a
negative control. RESULTS: We selected the intersection between 45,490 variants
from the mother and 45,646 variants from the son and excluded 27,512 overlapping
variants identified from the father. By excluding homogenous and compound
heterozygous variants and removing all previously reported variants, 147 variants
were identified to be shared by the mother and son. Variants that had least
proximities among species were excluded and finally 23 variants remained.
CONCLUSION: Among them, we identified a defect in parathyroid hormone like
hormone (PTHLH), encoding the PTH-related protein, to be disease-causative.
Herein, we report a family affected with brachydactyly type E2 caused by a novel
PTHLH mutation, which was confused with PPHP with unclassical genetic penetrance.
PMID- 29947180
TI - Prevalence and Annual Incidence of Thyroid Disease in Korea from 2006 to 2015: A
Nationwide Population-Based Cohort Study.
AB - BACKGROUND: The incidence of thyroid nodules has increased worldwide in recent
years. Thyroid dysfunction is a potential risk factor for hypercholesterolemia,
cardiovascular disease, osteoporosis, arrhythmia, and neuropsychiatric disease.
This study investigated the prevalence and annual incidence of thyroid nodules,
hypothyroidism, and hyperthyroidism in Koreans. METHODS: In this nationwide
population-based cohort study, 51,834,660 subjects were included using the
National Health Information database from 2006 to 2015, after the exclusion of
subjects with thyroid cancer. RESULTS: The prevalence in Korea in 2015 of thyroid
nodules, hypothyroidism in patients taking thyroid hormone, and hyperthyroidism
in patients undergoing treatment was 15.82/1,000 population, 15.94/1,000
population, and 2.76/1,000 population, respectively. All these diseases were more
prevalent among women than among men. The number of incident cases of these three
thyroid diseases steadily increased from 2006 to 2012, and then decreased through
2015. The incidence of thyroid nodules, hypothyroidism treated with thyroid
hormone, and treated hyperthyroidism was 6.79/1,000 population, 1.76/1,000
population, and 0.55/1,000 population, respectively, in Korea in 2015. The use of
methimazole continuously increased, from 33% of total antithyroid drug
prescriptions in 2006 to 74.4% in 2015, and it became the most frequently
prescribed antithyroid drug in Korea. In contrast, the use of propylthiouracil
continuously decreased. CONCLUSION: This was the first nationwide study of the
prevalence and annual incidence of thyroid nodules, hypothyroidism, and
hyperthyroidism to take into account recent changes and to include the current
status of patients receiving treatment.
PMID- 29947181
TI - The Status and Distinct Characteristics of Endocrine Diseases in North Korean
Articles Published between 2006 and 2015.
AB - BACKGROUND: Past decades of division have led to substantial differences in
medical environments between South and North Korea. However, little is known
about North Korea's medical status and research field, especially regarding
endocrinology. In this study, we report the characteristics of North Korea's
articles regarding endocrine-related diseases. METHODS: Among the nine medical
journals, articles published in Internal Medicine between 2006 and 2015 were
reviewed. A total of 2,092 articles were included; among them, 96 articles were
associated with endocrinology. We analyzed these articles according to the
disease categories they focused on and evaluated their features. RESULTS:
Articles related to diabetes mellitus accounted for 55.2% (n=53) and those to
thyroid disease accounted for 28.1% (n=27). Other disease categories, including
adrenal gland (n=1), pituitary gland (n=1), and osteoporosis (n=3), comprised
minor portions. Regarding diabetes mellitus, more than half the articles (n=33)
focused on treatment and complications. Experimental studies were conducted with
old hypoglycemic drugs or natural substances for the treatment of hyperglycemia.
Regarding thyroid disease, articles related to hyperthyroidism were the most
common (51.9%, n=14), followed by thyroid nodule/cancer (18.5%, n=5). Unique
article features were short length, no figures, and less than five references.
CONCLUSION: North Korea's endocrinology articles mainly focused on diabetes
mellitus and thyroid disease. Persistent studies have been carried out in North
Korea with dedication despite the poor medical environment. We hope that this
study will be the beginning of mutual medical exchange and collaboration between
North and South Korea.
PMID- 29947182
TI - Association between Serum Fibroblast Growth Factor 21 Levels and Bone Mineral
Density in Postmenopausal Women.
AB - BACKGROUND: Despite the beneficial effect of fibroblast growth factor 21 (FGF21)
on metabolic disease, there are concerns about adverse effects on bone
metabolism, supported by animal studies. However, a recent human study showed the
positive association between serum FGF21 level and bone mineral density (BMD) in
healthy premenopausal women. We undertook this study to examine the association
between FGF21 level and BMD in healthy postmenopausal Korean women who are
susceptible to osteoporosis. METHODS: We used data of 115 participants from a
cohort of healthy postmenopausal women (>50 years old) to examine the association
between serum FGF21 level and BMD. The clinical characteristics were obtained
from the participants, and blood testing and serum FGF21 testing were undertaken.
BMD of the lumbar spine, femoral neck and total hip area, and bone markers were
used in the analyses. RESULTS: The mean age of the participants was 60.2+/-7.2
years. Serum FGF21 levels showed negative correlation with BMD and T-scores in
all three areas, but there were no statistically significant differences.
Multivariate analyses with adjustment for age and body mass index also did not
show significant association between serum FGF21 level and BMD. In addition,
serum FGF21 level also showed no correlation with osteocalcin and C-telopeptide
levels. CONCLUSION: In our study, serum FGF21 level showed no significant
correlation with BMD and T-scores.
PMID- 29947183
TI - Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on
Papillary Thyroid Microcarcinoma (MAeSTro).
AB - BACKGROUND: The ongoing Multicenter Prospective Cohort Study of Active
Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the
natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for
active surveillance (AS), and compare the long-term prognosis, quality of life,
and medical costs between the AS and immediate surgery groups. METHODS: This
multicenter prospective cohort study of PTMC started in June 2016. The inclusion
criteria were suspicious of malignancy or malignancy based on fine needle
aspiration or core needle biopsy, age of >=18 years, and a maximum diameter of
<=1 cm. If there was no major organ involvement, no lymph node/distant
metastasis, and no variants with poor prognosis, the patients were explained of
the pros and cons of immediate surgery and AS before selecting AS or immediate
surgery. Follow-up visits (physical examination, ultrasonography, thyroid
function, and questionnaires) are scheduled every 6 months during the first 2
years, and then every 1 year thereafter. Progression was defined as a maximum
diameter increase of >=3, >=2 mm in two dimensions, suspected organ involvement,
or lymph node/distant metastasis. RESULTS: Among 439 enrolled patients, 290
patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The
median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group
had a larger maximum tumor diameter, compared to the AS group (7.1+/-1.9 mm vs.
6.6+/-2.0 mm, respectively; P=0.014). CONCLUSION: The results will be useful for
developing an appropriate PTMC treatment policy based on its natural course and
risk factors for progression.
PMID- 29947184
TI - Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A
Multicenter Study in Korea.
AB - BACKGROUND: Most patients with differentiated thyroid cancer (DTC) have a
favorable prognosis. However, patients with DTC and initial distant metastasis
have not been commonly found, and their clinical characteristics have seldom been
reported. In this study, we analyzed the clinical features and prognosis of
patients with DTC and initial distant metastasis in Korea. METHODS: We
retrospectively reviewed the clinical data of 242 patients with DTC and initial
distant metastasis treated from 1994 to 2013, collected from five tertiary
hospitals in Korea. RESULTS: The patients' median age was 51 years, and 65% were
women. They were followed for a median of 7 years. Lung was the most common site
of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other
single site one (pleura), and combined sites 43 (40 were lung and bone, two were
bone and other site, and one was lung and other site). At the time of diagnosis,
50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease
specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than
those in previous studies. After multivariate analysis, old age, male sex,
metastatic site, and histologic type (follicular type) were significant factors
for poor prognosis. However, negative RAI avidity status was not a significant
prognostic factor after adjusting for other variables. CONCLUSION: The prognosis
of Korean patients with DTC and initial distant metastasis was better than in
previous studies. Old age, male sex, metastasis site, and histologic type were
significant prognostic factors.
PMID- 29947185
TI - Influence of Vitamin D Deficiency on Progression of Experimental Otitis Media in
Rats.
AB - BACKGROUND: Vitamin D plays an important role in the immune response against
infection. The purpose of the present study was to investigate the influence of
vitamin D deficiency on the progression of otitis media (OM) using an
experimental rat model. METHODS: Four-week-old male Sprague-Dawley rats (n=72)
were divided into two groups based on their diet: a control diet group (n=36) and
a vitamin D-deficient diet group (n=36). After 8 weeks of diet, experimental OM
was induced by inoculation of non-typeable Haemophilus influenzae in the middle
ear cavity. The rats were evaluated with otomicroscopy to determine the
inflammation in the middle ear mucosa on days 1, 2, 4, 7, and 14 post
inoculation. Bullae from sacrificed rats were collected and analyzed
histologically. RESULTS: The middle ear mucosa from rats with vitamin D
deficiency showed a significantly higher thickness than that of controls during
the course of OM. The maximum mucosal thickness was 56.0+/-9.1 MUm in the vitamin
D deficiency group, and 43.9+/-9.8 MUm in the control group, although there was
no significant difference in the tympanic membrane score between the two groups
evaluated with otomicroscopy. An immunohistochemical study showed increased
expression of interleukin 6 (IL-6) and tumor necrosis factor alpha in rats
manifesting vitamin D deficiency and decreased expression of IL-10 compared with
controls. CONCLUSION: Our results showed that vitamin D deficiency may exacerbate
the pathophysiological changes of OM via altered cytokine production. Therefore,
maintaining vitamin D status in the optimal range may be beneficial for proper
management of OM.
PMID- 29947187
TI - ?
PMID- 29947186
TI - The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes
Development: The Kangbuk Samsung Health Study (Endocrinol Metab 2018;33:55-61, Yu
Hyun Kwon et al.).
PMID- 29947188
TI - A doctor in the minority.
PMID- 29947190
TI - ?
PMID- 29947189
TI - ?
PMID- 29947191
TI - ?
PMID- 29947192
TI - ?
PMID- 29947193
TI - ?
PMID- 29947194
TI - ?
PMID- 29947195
TI - ?
PMID- 29947196
TI - The power of diagnosis.
PMID- 29947197
TI - ?
PMID- 29947198
TI - ?
PMID- 29947199
TI - ?
PMID- 29947200
TI - ?
PMID- 29947201
TI - Spontaneous pneumomediastinum.
PMID- 29947202
TI - ?
PMID- 29947203
TI - Fertility after cryopreservation of ovarian tissue due to cancer treatment.
AB - BAKGRUNN: Kryopreservering av ovarialvev som fertilitetsbevarende metode tilbys
prepubertale jenter og kvinner i reproduktiv alder med hoy risiko for a utvikle
prematur ovarialsvikt i forbindelse med medisinsk eller kirurgisk behandling. I
denne studien onsket vi a kartlegge fertilitet og prematur ovarialsvikt hos
kvinner som har fatt gjort kryopreservering av ovarialvev i forbindelse med
kreftbehandling. MATERIALE OG METODE: Et sporreskjema ble i 2014 sendt til 94
kvinner over 18 ar som i perioden 2004-12 hadde fatt kryopreservert ovarialvev i
forbindelse med behandling for en malign tilstand. Skjemaet inneholdt sporsmal om
menstruasjonsfrekvens, prevensjonsbruk, fertilitet, fremtidig barneonske og
sannsynlighet for at de ville benytte ovarialvevet senere. Av de 77 kvinnene som
returnerte sporreskjemaet, ble 74 kvinner inkludert i studien. RESULTATER: Totalt
20 av 74 kvinner (27 %) hadde prematur ovarialsvikt definert som opphor av
ovarialfunksjonen for 40 ars alder. Risikoen var lavest hos kvinner behandlet for
brystkreft (5 %) og hoyest hos kvinner behandlet for leukemi (75 %). Storst
risiko for prematur ovarialsvikt fant man i pasientgruppene som hadde gjennomgatt
stamcelletransplantasjon, stralebehandling mot helkropp og/eller abdomen og
bekken. Til sammen hadde 22 kvinner fodt 31 barn etter kreftbehandlingen, hvorav
to etter reimplantasjon av ovarialvev. FORTOLKNING: Risikoen for a utvikle
prematur ovarialsvikt er avhengig av pasientens kreftdiagnose. Hvilke
fertilitetsbevarende tiltak som anbefales, bor differensieres avhengig av
pasienten kreftdiagnose og planlagt behandling.
PMID- 29947204
TI - Augusta Rasmussen - psychiatrist, pioneer and the scientific truths of the time.
AB - In 1934, senior registrar Augusta Rasmussen (1895-1979) published a study of 77
cases involving sexual offences. She found that the women involved had suffered
no mental injury from the abuse. In 1947, she published a study of the
intelligence level of 310 Norwegian women who had formed relationships with
German soldiers during the occupation. She found that nearly all of them were
more or less retarded. Her conclusions, however, were not scientifically valid.
Here we present Rasmussen's biography, academic background and scientific
activity.
PMID- 29947205
TI - ?
PMID- 29947206
TI - Physical exercise in adults with hereditary neuromuscular disease.
PMID- 29947207
TI - ?
PMID- 29947208
TI - Serotonin or society?
PMID- 29947209
TI - ?
AB - BACKGROUND: Following the bomb attack on the government quarter on 22 July 2011,
many of the injured were treated at the accident and emergency department in
Oslo. MATERIAL AND METHOD: The patients (n=79) were sent a questionnaire ten
months after their treatment and again after three years. A total of 42 patients
responded on one or both occasions. Post-traumatic stress reactions were measured
using PTSD-RI (University of California at Los Angeles PTSD Reaction Index).
Symptoms of anxiety and depression were measured with the aid of HSCL-8 (Hopkins
Symptom Checklist). Physical symptoms were surveyed using twelve questions.
Satisfaction with follow-up was measured with eight questions on a five-point
scale. RESULTS: After ten months, the average score for PTSD-RI was 1.4 (95 % CI
1.0-1.7), and 31 % of the responses were at a clinical PTSD level. After three
years, the average score was 1.3 (95 % CI 0.9-1.7), and 25 % were at a clinical
PTSD level. Symptom score for anxiety and depression after ten months was 0.9 (95
% CI 0.6-1.2) and after three years 0.8 (95 % CI 0.5-1.2). The most frequent
physical symptom was headache. The satisfaction with follow-up varied somewhat
but was generally good. INTERPRETATION: Several patients who received treatment
for injuries at the accident and emergency department in Oslo had mental symptoms
for a long period following the terror attack. The patients were satisfied with
the follow-up, which was mainly provided by the primary healthcare service.
PMID- 29947210
TI - Accumulative Polarization Reversal in Nanoscale Ferroelectric Transistors.
AB - The electric-field-driven and reversible polarization switching in ferroelectric
materials provides a promising approach for nonvolatile information storage. With
the advent of ferroelectricity in hafnium oxide, it has become possible to
fabricate ultrathin ferroelectric films suitable for nanoscale electronic
devices. Among them, ferroelectric field-effect transistors (FeFETs) emerge as
attractive memory elements. While the binary switching between the two logic
states, accomplished through a single voltage pulse, is mainly being investigated
in FeFETs, additional and unusual switching mechanisms remain largely unexplored.
In this work, we report the natural property of ferroelectric hafnium oxide,
embedded within a nanoscale FeFET, to accumulate electrical excitation, followed
by a sudden and complete switching. The accumulation is attributed to the
progressive polarization reversal through localized ferroelectric nucleation. The
electrical experiments reveal a strong field and time dependence of the
phenomenon. These results not only offer novel insights that could prove critical
for memory applications but also might inspire to exploit FeFETs for
unconventional computing.
PMID- 29947211
TI - Three-Dimensional DNA Origami as Programmable Anchoring Points for Bioreceptors
in Fiber Optic Surface Plasmon Resonance Biosensing.
AB - Many challenges in biosensing originate from the fact that the all-important
nanoarchitecture of the biosensor surface, including precise density and
orientation of bioreceptors, is not entirely comprehended. Here, we introduced a
three-dimensional DNA origami as a bioreceptor carrier to functionalize the fiber
optic surface plasmon resonance (FO-SPR) sensor with nanoscale precision.
Starting from a 24-helix bundle, two distinct DNA origami structures were
designed to position thrombin-specific aptamers with different densities and
distances (27 and 113 nm) from the FO-SPR surface. The origami-based biosensors
not only proved to be capable of reproducible, label-free thrombin detection but
revealed also valuable innovative features: (1) a significantly better
performance in the absence of backfilling, known as essential in the biosensing
field, suggesting improved bioreceptor orientation and accessibility, and (2) a
wider linear range compared to previously reported thrombin biosensors. We
envisage that our method will be beneficial for both scientists and clinicians
looking for new surface (bio)chemistry and improved diagnostics.
PMID- 29947212
TI - Particle Diffusion in Polymeric Hydrogels with Mixed Attractive and Repulsive
Interactions.
AB - All biogels are heterogeneous, consisting of functional groups with different
biophysical properties arrayed on spatially disordered polymer networks.
Nanoparticles diffusing in such biogels experience a mixture of attractive and
repulsive interactions. Here, we present experimental and theoretical studies of
charged particle diffusion in gels with a random distribution of attractive and
repulsive electrostatic interaction sites inside the gel. In addition to
interaction disorder, we theoretically investigate the effect of spatial disorder
of the polymer network. Our coarse-grained simulations reveal that attractive
interactions primarily determine the diffusive behavior of the particles in
systems with mixed attractive and repulsive interactions. As a consequence,
charged particles of either sign are immobilized in mixed cationic/anionic gels
because they are trapped near oppositely charged interaction sites, whereas
neutral particles diffuse rapidly. Even small fractions of oppositely charged
interaction sites lead to strong trapping of a charged particle. Translational
diffusion coefficients of charged probe molecules in gels consisting of mixed
cationic and anionic dextran polymers are determined by fluorescence correlation
spectroscopy and quantitatively confirm our theoretical predictions.
PMID- 29947213
TI - Dual-Functional Dendritic Mesoporous Bioactive Glass Nanospheres for Calcium
Influx-Mediated Specific Tumor Suppression and Controlled Drug Delivery in Vivo.
AB - The development of nanomaterials for stable, controlled delivery of drugs and
efficient suppression of tumor growth with desirable biosafety remains
challenging in the nano-biomedical field. In this study, we prepared and
optimized mesoporous bioactive glass (MBG) nanospheres to establish a functional
drug delivery system and analyzed the effect of the dendritic mesoporous
structure on drug loading and release. We then utilized an in vitro model to
examine the biological effects of dendritic MBG nanospheres on normal and tumor
cells and studied the molecular mechanism underlying specific tumor suppression
by MBG nanospheres. Finally, we investigated the combinational effect of MBG
nanospheres and a cancer therapeutic drug with an in vivo tumor xenograft model.
Our results show that the dendritic MBG nanospheres have been successfully
synthesized by optimizing calcium: silicon ratio. MBG nanospheres exhibit a
dendritic mesoporous structure with a large specific surface area, demonstrate
high drug loading efficiency, and release drugs in a controlled fashion to
effectively prolong drug half-life. Ca2+ in nanospheres activates transient
receptor potential channels and calcium-sensing receptor on tumor cells, mediates
calcium influx, and directly regulates the calpain-1-Bcl-2-caspase-3 signaling
pathway to specifically suppress tumor growth without affecting normal cells. In
addition, dendritic MBG nanospheres synergize with cancer drugs to improve
antitumor efficacy and reduce systemic toxicity. Dendritic MBG nanospheres with
antitumor activity and controlled drug release have been successfully achieved
and the underlying molecular mechanism was elucidated, paving the way for
translational application.
PMID- 29947214
TI - Waterborne and Dietborne Toxicity of Inorganic Arsenic to the Freshwater
Zooplankton Daphnia magna.
AB - Waterborne and dietborne exposure are both important sources for the accumulation
of inorganic arsenic (iAs) in aquatic organisms. Although the waterborne toxicity
of iAs has been extensively investigated, its dietborne toxicity has received
little attention. The present study examined the acute and chronic toxicity of
arsenate (iAsV) and arsenite (iAsIII) to the freshwater zooplankton species
Daphnia magna under both waterborne and dietborne exposure scenarios. The
bioaccumulation, speciation, and tissue and subcellular distributions of arsenic
were analyzed to understand the mechanisms accounting for differences in toxicity
related to different arsenic species, exposure scenarios, and exposure duration.
The toxicity of iAs increased with exposure time, and iAsIII was more toxic than
iAsV. Moreover, although dietborne iAs had no acute effect on D. magna, it
incurred significant toxicity in the chronic-exposure experiment. Nevertheless,
the toxicity of dietborne iAs was still lower than that of waterborne iAs
regardless of the exposure duration. This difference was found to be caused by
the lower bioaccumulation of dietborne iAs, its higher distribution in the gut
and in the biologically detoxified subcellular fraction, and greater
transformation to the less toxic dimethylarsinic acid. Overall, the dietborne
toxicity of iAs should be considered when evaluating the environmental risks
posed by arsenic.
PMID- 29947215
TI - Enhanced Performance of Microarchitectured PTFE-Based Triboelectric Nanogenerator
via Simple Thermal Imprinting Lithography for Self-Powered Electronics.
AB - Triboelectric nanogenerator (TENG) technology is an emerging field to harvest
various kinds of mechanical energies available in our living environment.
Nowadays, for industrial and large-scale area applications, developing the TENG
with low device processing cost and high electrical output is a major issue to be
resolved. Herein, we designed a TENG with low cost by employing the microgrooved
architectured (MGA)-poly(tetrafluoroethylene) (PTFE; Teflon) and aluminum as
triboelectric materials with opposite tendencies. Moreover, the MGA-PTFE was
fabricated by a single-step, facile, and cost-effective thermal imprinting
lithography technique via micropyramidal textured silicon as a master mold,
fabricated by a wet-chemical etching method. Therefore, designing the TENG device
by following these techniques can definitely reduce its manufacturing cost.
Additionally, the electrical output of TENG was enhanced by adjusting the
imprinting parameters of MGA-PTFE. Consequently, the MGA-PTFE was optimized at an
imprinting pressure and temperature of 5 MPa and 280 degrees C, respectively.
Thus, the TENG with an optimal MGA-PTFE polymer exhibited the highest electrical
output. A robustness test of TENG was also performed, and its output power was
used to drive light-emitting diodes and portable electronic devices. Finally, the
real application of TENG was also examined by employing it as a smart floor and
object-falling detector.
PMID- 29947216
TI - Graphene-Based Adaptive Thermal Camouflage.
AB - In nature, adaptive coloration has been effectively utilized for concealment and
signaling. Various biological mechanisms have evolved to tune the reflectivity
for visible and ultraviolet light. These examples inspire many artificial systems
for mimicking adaptive coloration to match the visual appearance to their
surroundings. Thermal camouflage, however, has been an outstanding challenge
which requires an ability to control the emitted thermal radiation from the
surface. Here we report a new class of active thermal surfaces capable of
efficient real-time electrical-control of thermal emission over the full infrared
(IR) spectrum without changing the temperature of the surface. Our approach
relies on electro-modulation of IR absorptivity and emissivity of multilayer
graphene via reversible intercalation of nonvolatile ionic liquids. The
demonstrated devices are light (30 g/m2), thin (<50 MUm), and ultraflexible,
which can conformably coat their environment. In addition, by combining active
thermal surfaces with a feedback mechanism, we demonstrate realization of an
adaptive thermal camouflage system which can reconfigure its thermal appearance
and blend itself with the varying thermal background in a few seconds.
Furthermore, we show that these devices can disguise hot objects as cold and cold
ones as hot in a thermal imaging system. We anticipate that, the electrical
control of thermal radiation would impact on a variety of new technologies
ranging from adaptive IR optics to heat management for outer space applications.
PMID- 29947217
TI - Single-Ring Magnetic Levitation Configuration for Object Manipulation and Density
Based Measurement.
AB - Magnetic levitation is a recent research hot spot; however, most of the extant
configurations use two magnets with like poles facing each other. This paper
proposes a novel magnetic levitation configuration that is based on a single ring
magnet, and this configuration opens a wide operational space that enables object
manipulation and density-based measurement. We develop a mathematical model to
calculate the magnetic field around the magnet and to numerically correlate the
levitation height and density of the object. Experimental results prove that this
novel configuration can achieve a high accuracy (+/-0.0005 to +/-0.0078 g/cm3) in
density measurement for small-sized (~5 MUL) samples. It can manipulate
particles, powders, and oil droplets effectively without any direct contact, and
it has high sensitivity in the separation of multiple diamagnetic objects with
slight differences in densities as well. The accuracy and sensitivity of the
proposed configuration are both higher than those of the extant configurations.
All of these results are expected to promote deeper study and applications of the
magnetic levitation configuration in the field of density-based characterizations
and manipulations.
PMID- 29947218
TI - Multiscale Coupling Strategy for Nano Ecotoxicology Prediction.
PMID- 29947219
TI - Langevin Approach to Modeling of Small Levitating Ordered Droplet Clusters.
AB - A self-assembled cluster of microdroplets levitating over a heated water surface
is a fascinating phenomenon with potential applications for microreactors and for
chemical and biological analysis of small volumes of liquids. Recently, we
suggested a method to synthesize a cluster with an arbitrary number of small
monodisperse droplets. However, the interactions, which control the structure of
the cluster, are still not well understood. Here we propose a Langevin
computational model considering the aerodynamic forces between the droplets and
random diffusion-like fluctuations. Characteristic length and time scales and
scaling relationships of interactions are discussed. The model shows excellent
agreement with experimental observations for a small number of droplets.
PMID- 29947220
TI - Human Metabolome Changes after a Single Dose of 3,4-Methylenedioxymethamphetamine
(MDMA) with Special Focus on Steroid Metabolism and Inflammation Processes.
AB - The intake of 3,4-methylenedioxymethamphetamine (MDMA) is known to increase
several endogenous substances involved in steroid and inflammation pathways.
Untargeted metabolomics screening approaches can determine biochemical changes
after drug exposure and can reveal new pathways, which might be involved in the
pharmacology and toxicology of a drug of abuse. We analyzed plasma samples from a
placebo-controlled crossover study of a single intake of MDMA. Plasma samples
from a time point before and three time points after the intake of a single dose
of 125 mg MDMA were screened for changes of endogenous metabolites. An untargeted
metabolomics approach on a high-resolution quadrupole time-of-flight mass
spectrometer coupled to liquid chromatography with two different chromatographic
systems (reversed-phase and hydrophobic interaction liquid chromatography) was
applied. Over 10 000 features of the human metabolome were detected. Hence, 28
metabolites were identified, which showed significant changes after
administration of MDMA compared with placebo. The analysis revealed an
upregulation of cortisol and pregnenolone sulfate 4 h after MDMA intake,
suggesting increased stress and serotonergic activity. Furthermore, calcitriol
levels were decreased after the intake of MDMA. Calcitriol is involved in the
upregulation of trophic factors, which have protective effects on brain dopamine
neurons. The inflammation mediators hydroxyeicosatetraenoic acid,
dihydroxyeicosatetraenoic acid, and octadecadienoic acid were found to be
upregulated after the intake of MDMA compared with placebo, which suggested a
stimulation of inflammation pathways.
PMID- 29947221
TI - Self-Calibrating On-Chip Localized Surface Plasmon Resonance Sensing for
Quantitative and Multiplexed Detection of Cancer Markers in Human Serum.
AB - The need for point-of-care devices able to detect diseases early and monitor
their status, out of a lab environment, has stimulated the development of compact
biosensing configurations. Whereas localized surface plasmon resonance (LSPR)
sensing integrated into a state-of-the-art microfluidic chip stands as a
promising approach to meet this demand, its implementation into an operating
sensing platform capable of quantitatively detecting a set of molecular
biomarkers in an unknown biological sample is only in its infancy. Here, we
present an on-chip LSPR sensor capable of performing automatic, quantitative, and
multiplexed screening of biomarkers. We demonstrate its versatility by
programming it to detect and quantify in human serum four relevant human serum
protein markers associated with breast cancer.
PMID- 29947222
TI - Controlled Deposition Number of Organic Molecules Using Quartz Crystal
Microbalance Evaluated by Scanning Tunneling Microscopy Single-Molecule-Counting.
AB - Precise control of organic molecule deposition on a substrate is quite important
for fabricating single-molecule-based devices. In this study, we demonstrate
whether a quartz-crystal microbalance (QCM) widely used for a film growth
calibration has the ability to precisely measure the number of organic molecules
adsorbed on a substrate. The well-known Sauerbrey's equation is extended to
formulate the relation between QCM resonant frequency shift and the number of
adsorbed molecules onto the QCM surface. The formula is examined by QCM
measurements of sublimation of pi-conjugated organic molecules and direct
counting of the deposited molecules one by one onto metal substrates, using
ultrahigh vacuum low-temperature scanning tunneling microscopy (STM). It is
revealed that the number of adsorbed molecules evaluated by QCM ( NQCM) show good
agreement with those counted from the STM images ( NSTM) within the error of +/
25%. The results ensure the QCM capability for controlling the deposition number
of organic molecules with high accuracy, that is, if one needs to deposit 100
molecules on the substrate, QCM control promises deposition of 100 +/- 25
molecules.
PMID- 29947223
TI - Biodegradable Zwitterionic Nanogels with Long Circulation for Antitumor Drug
Delivery.
AB - Zwitterionic nanocarriers have emerged as a new class of biocompatible
nanomaterials with outstanding stealth capability in blood circulation. In this
work, a novel biodegradable zwitterionic nanogel based on poly(sulfobetaine
methacrylate) (PSBMA) was developed for reduction-responsive drug delivery to
tumors. PSBMA nanogels were facilely fabricated by one-step reflux precipitation
polymerization with the advantage of being surfactant-free and time-saving. The
disulfide bond not only endowed the nanogels degradability in a reduction
environment but also be modified with a fluorescent group after partial
reduction. In vitro release experiments disclosed that doxorubicin (DOX)-loaded
PSBMA nanogels could hold the drugs firmly in physiological conditions (only 7%
release in 24 h) and release the drugs rapidly and sufficiently in 10 mM
glutathione (85% in 8 h). More interestingly, PSBMA nanogels displayed long
circulation in blood after intravenous injection, and small change was found in
half-life of nanogels between the first (34.1 h) and the second injection (30.5
h), indicating that there was no accelerated blood clearance phenomenon for these
nanogels. Meanwhile, no obvious immunogenic response was detected after PSBMA
nanogels were injected into BALB/c mice. Furthermore, PSBMA nanogels showed a
high accumulation of 9.5 and 10.7% of injected dose per gram of tissue in tumors
at 24 and 48 h post intravenous injection, respectively. With outstanding long
circulation time, high tumor accumulation, and sufficient drug release in a
reduction environment, DOX-loaded PSBMA nanogels demonstrated the strongest tumor
growth inhibition effect among all of the treatment groups in human
hypopharyngeal carcinoma-bearing mouse models. Therefore, our study provided a
facile drug delivery platform based on biodegradable zwitterionic nanogels and
may have great potential in tumor drug delivery.
PMID- 29947224
TI - Efficient and Deterministic Propagation of Mixed Quantum-Classical Liouville
Dynamics.
AB - We propose a highly efficient mixed quantum-classical molecular dynamics scheme
based on a solution of the quantum-classical Liouville equation (QCLE). By
casting the equations of motion for the quantum subsystem and classical bath
degrees of freedom onto an approximate set of coupled first-order differential
equations for c-numbers, this scheme propagates the composite system in time
deterministically in terms of independent classical-like trajectories. To
demonstrate its performance, we apply the method to the spin-boson model, a
photoinduced electron transfer model, and a Fenna-Matthews-Olsen complex model,
and find excellent agreement out to long times with the numerically exact
results, using several orders of magnitude fewer trajectories than surface
hopping solutions of the QCLE. Owing to its accuracy and efficiency, this method
promises to be very useful for studying the dynamics of mixed quantum-classical
systems.
PMID- 29947225
TI - Studies on the Synthesis of Phlegmarine-Type Lycopodium Alkaloids:
Enantioselective Synthesis of (-)-Cermizine B, (+)-Serratezomine E, and (+)
Luciduline.
AB - The synthesis of the Lycopodium alkaloids, (-)-cermizine B, (+)-serratezomine E,
and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral
scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation
reaction between ( R)- or ( S)-phenylglycinol and the substituted delta-keto
ester 11, easily accessible from ( R)-pulegone. The factors governing the
stereoselectivity of these cyclocondensation reactions are discussed. Key steps
of the synthesis from the stereochemical standpoint are the stereoselective
elaboration of the allyl substituent to the ( S)-2-(piperidyl)methyl moiety and
the stereoselective removal of the chiral inductor to give a cis
decahydroquinoline.
PMID- 29947227
TI - Cone Snail Glutaminyl Cyclase Sequences from Transcriptomic Analysis and Mass
Spectrometric Characterization of Two Pyroglutamyl Conotoxins.
AB - The post-translational modification of N-terminal glutamine (Q) to a pyroglutamyl
(Z) residue is observed in the conotoxins produced by marine cone snails. This
conversion requires the action of the enzyme glutaminyl cyclase (QC). Four
complete QC sequences from the species C. araneosus, C. frigidus, C. litteratus,
and C. monile and two partial sequences from C. amadis and C. miles have been
obtained by analysis of transcriptomic data. Comparisons with mammalian enzyme
sequences establish a high level of identity and complete conservation of
functional active site residues, including a cluster of hydrogen-bonded acidic
side chains. Mass spectrometric analysis of crude venom samples coupled to
conotoxin precursor protein sequences obtained from transcriptomic data
establishes the presence of pyroglutamyl conotoxins in the venom of C. frigidus
and C. amadis. The C. frigidus peptide belongs to the M superfamily, with
cysteine framework III, whereas the C. amadis peptide belongs to the divergent
superfamily with cysteine framework VI/VII. Additionally, gamma carboxylation of
glutamic acid and hydroxylation of proline are observed in the C. frigidus
peptide. Mass spectral data are available via ProteomeXchange with identifier
PXD009006.
PMID- 29947226
TI - Ultrathin Metal-Organic Framework Nanosheet-Derived Ultrathin Co3O4 Nanomeshes
with Robust Oxygen-Evolving Performance and Asymmetric Supercapacitors.
AB - Ultrathin metal-organic framework (MOF) nanosheets possessing inherent advantages
of both two-dimensional (2D) features and MOFs are attracting intensive research
interest. The direct manufacture of MOF nanosheets is still a challenge up to
now. Here, we have developed a novel bottom-up approach to synthesize zeolitic
imidazolate framework-67 (ZIF-67) nanosheets, which can be in situ converted into
Co3O4 ultrathin nanomeshes after thermal treatment. Interestingly, the obtained
Co3O4 nanomeshes are rich in oxygen defects, providing fruitful active sites for
the faradaic reaction. The modified electrode exhibits a large specific
capacitance (1216.4 F g-1 at 1 A g-1), as well as a high rate capability (925.5 F
g-1 at 20 A g-1). Moreover, an asymmetric supercapacitor made of Co3O4//activated
carbon shows an energy density of 46.5 Wh kg-1 at 790.7 W kg-1. Furthermore, the
2D Co3O4 ultrathin nanomeshes show an outstanding performance for the oxygen
evolution reaction with an overpotential of 230 mV at the onset potential and a
small Tafel slope of 74.0 mV dec-1. The present method presents a facile avenue
to the preparation of other 2D ultrathin metal oxide nanostructures with various
applications in energy catalysis and conversion.
PMID- 29947228
TI - Highly Sensitive, Printable Nanostructured Conductive Polymer Wireless Sensor for
Food Spoilage Detection.
AB - Near-field communication (NFC) labeling technology has been recently used to
endow smartphones with nonline-of-sight sensing functions to improve the
environment, human health, and quality of life. For applications in detecting
food spoilage, the development of a sensor with high enough sensitivity to act as
a switch for an NFC tag remains a challenge. In this Letter, we developed a
nanostructured conductive polymer-based gas sensor with high sensitivity of Delta
R/ R0 = 225% toward 5 ppm ammonia NH3 and unprecedented sensitivities of 46% and
17% toward 5 ppm putrescine and cadaverine, respectively. The gas sensor plays a
critical role as a sensitive switch in the circuit of the NFC tag and enables a
smartphone to readout meat spoilage when the concentration of biogenic amines is
over a preset threshold. We envision the broad potential use of such intelligent
sensing for food status monitoring applications in daily life, storage and supply
chains.
PMID- 29947229
TI - Multimedia Distribution and Transfer of Per- and Polyfluoroalkyl Substances
(PFASs) Surrounding Two Fluorochemical Manufacturing Facilities in Fuxin, China.
AB - Industrial facilities can be point sources of per- and polyfluoroalkyl substances
(PFASs) emission to the surrounding environment. In this study, 25 neutral and
ionizable PFASs were analyzed in 94 multimedia samples including air, rain,
outdoor settled dust, soil, plant leaves, river water, surface sediment, and
shallow groundwater from two fluorochemical manufacturing parks (FMPs) in Fuxin,
China, to elucidate the multimedia distribution and transfer pattern of PFASs
from a point source. The concentrations of individual PFASs in air, outdoor
settled dust, and surface river water decreased exponentially as the distance
increases from the FMPs, whereas the concentrations of short-chain (C2-C4)
perfluoroalkyl carboxylic acids (PFCAs) remained high (3000 ng/L) in the surface
water 38 km away. At FMPs, air concentrations of fluorotelomer alcohols and
iodides were found dominant with levels of up to 7900 pg/m3 and 920 pg/m3,
respectively. Trifluoroacetic acid was directly released from FMPs and occurred
in all the environmental matrices at levels 1-2 orders of magnitude higher than
other PFCAs. Higher air-water concentration ratios of short-chain PFCAs (C2-C4)
suggested their transfer tendency from air to water. Both short-chain (C2) and
long-chain (>C6) PFCAs have greater sediment-water distribution coefficients and
deposit dust-air coefficients, which have great influences on the long-range
transport potential of different analogues.
PMID- 29947230
TI - Eisenmenger syndrome - an electrocardiographic and echocardiographic assessment
of the right ventricle.
AB - BACKGROUND: Eisenmenger syndrome represents severe, irreversible, and end-stage
pulmonary arterial hypertension (PAH) associated with congenital heart defects.
For long-term outcome optimal right ventricular (RV) adaptation is crucial with
precise assessment of its hypertrophy, dilatation and function. OBJECTIVES:
Associations of electrocardiographic (ECG) and echocardiographic (ECHO) RV
characteristics were analyzed. METHODS: Included were 52 patients (39F/13M),
median age 45 years (24-78). Following ECG parameters were analyzed: Butler
Leggett formula (B-L), Sokolow-Lyon criterion (S-L), QRS duration (QRS), maximum
spatial QRS vector magnitude (QRS max); and ECHO parameters: RV diameter (RVd),
RV wall thickness (RVAW), RV/LV function. RESULTS: Following significant ECG-ECHO
associations were demonstrated: S-L criterion and B-L formula with RVAW (p 120 ms
only with severely dilated RV (RVd > 45 mm), while QRS max 33 mm); A new combined
scoring system was introduced. CONCLUSIONS: In Eisenmenger syndrome RV
hypertrophy is compensatory; diagnosis of prognostically unfavorable RV
dilatation is therefore important. Combined ECG-ECHO analysis enables more
accurate risk stratification. QRS duration > 120 ms seems to be a late marker;
QRS max together with ECHO parameters may help to distinguish patients at higher
risk for clinical deterioration (Tab. 3, Fig. 8, Ref. 53).
PMID- 29947232
TI - Relationship between red cell distribution width and mean platelet volume with
new onset atrial fibrillation afteroff-pump coronary artery bypass grafting.
AB - OBJECTIVE: The aim of this study was to evaluate the relationship between red
blood cell distribution width (RDW) and mean platelet volume (MPV) with
development of postoperative atrial fibrillation (PoAF) after off-pump coronary
artery bypass grafting (CABG). BACKGROUND: The RDW and MPV have been associated
with some cardiovascular disorders. METHODS: A total of 93 patients who underwent
off-pump CABG were included in this study. The patients were divided into two
groups as developing and nondeveloping PoAF groups in the postoperative period.
We measured whether RDW and MPV levels are a predictive value for development
PoAF. RESULTS: There were 24 patients with PoAF enrolled (mean age: 66 +/- 7.8
years) and 69 patients without PoAF (mean age: 56.26 +/- 11.53 years). The PoAF
was significantly correlated with age (p = 0.004), hematocrit (p: 0.010), RDW (p
= 0.007) and creatinine (p = 0.006). Only advanced age (p = 0.012) was identified
as an independent predictor of PoAF. For predicting PoAF, there was 79.2 %
sensitivity and 65.2 % specificity for RDW (p = 0.001) and 62.5 % sensitivity and
55.1 % specificity for MPV (p = 0.062). CONCLUSIONS: We found that RDW levels and
MPV were not an independent predictor of the development of PoAF. However,
elevated RDW levels and MPV may be one of the predictive values for PoAF
development (Tab. 3, Fig. 2, Ref. 27).
PMID- 29947231
TI - Single umbilical artery and reproduction losses in Slovak population: relation to
karyotype and fetal anomalies.
AB - AIM: The purpose of this study was to monitor the association between single
umbilical artery (SUA), chromosomal abnormalities and associated anomalies during
the routine examination of spontaneous or induced miscarriages and premature
births. METHODS: During 1992-2015 we morphologically and cytogenetically examined
a series of 4098 samples. For 1330 cases the number of umbilical cord vessels
could be reported. RESULTS: The presence of single umbilical artery was
identified in 67 fetuses of 1330 pregnancies (5.04 %); 36 of the 67 fetuses (53.7
%) had additional congenital malformations. The cultures were unsuccessful in 29
of 67 cases (43.3 %). 38 cases (56.7 %) were successfully karyotyped; 20 out of
them had a normal karyotype and 18 had chromosomal anomalies including trisomy 18
(n = 4), trisomy 13 (n = 3), trisomy 21 (n = 2), trisomy 11 (n = 1), triploidy (n
= 3), monosomy X (n = 3) and structural chromosomal aberrations (n = 2).
CONCLUSION: Isolated SUA is not at increased risk of chromosomal abnormalities
and generally does not endanger pregnancy. All chromosomally abnormal embryos and
fetuses had associated congenital anomalies. The most frequently associated
congenital anomalies were in the musculoskeletal system, central nervous system
and genitourinary tract (Tab. 4, Ref. 44).
PMID- 29947233
TI - MicroRNAs in pathophysiology of acute myocardial infarction and cardiogenic
shock.
AB - AIM: Levels of circulating miRNA are considered to be potential biomarkers of
acute myocardial infarction and disease progression. METHODS: In this study, the
expression levels of circulating miRNA-1, miRNA-133 and miRNA-124a were
investigated in a group of patients with acute myocardial infarction (STEMI) and
cardiogenic shock (CS) compared to controls. RESULTS: During the hospitalization
period, miRNA-133 showed a significant up-regulation in the serum of STEMI and CS
patients compared to controls, while the expression of miRNA-1 was significantly
different only in CS. The expression of miRNA-124 was significantly higher in
STEMI and CS. Furthermore, miRNA-1 expression was related to the level of
circulating glucose in patients with STEMI. We also found a negative correlation
between miRNA-133 and MMP-9 levels. MiRNA-124 expression was significantly
related to the level of soluble ST2; the marker correlated to cardiac damage.
CONCLUSION: All selected miRNAs are potential markers of cardiac injury in
cardiogenic shock, whereas miRNA-124a and -133 are markers of injury in STEMI.
MiRNA-1 expression is related to circulating glucose in STEMI. None of miRNAs
could be correlated to the extent of injury, progress of the disease, or
prognosis of patient outcome. Therefore, the levels of circulating miRNA have no
potential for becoming a biomarker of myocardial damage and as such would bring
no further benefit compared to current markers (Tab. 4, Fig. 1, Ref. 47).
PMID- 29947234
TI - Effects of apelin-13 on myocardial ischemia reperfusion injury in streptozotocine
induced diabetic rats.
AB - AIM: We want to investigate the protective effects of apelin-13 on myocardial
ischemia reperfusion (I/R) injury. MATERIAL AND METHODS: 30 Wistar Albino rat
were divided into 5 groups (n:6), namely control group (C), diabetes group (D),
diabetes+apelin-13 group (DA), diabetes+I/R group (DIR) and diabetes I/R+apelin
13 group (DIR-A). Rats were subjected to 30-min ischemia and 90-min reperfusion.
Biochemical and histopathological parameters were measured. RESULTS: Caspase-3
enzyme activity was significantly higher in the DIR group than in the C, DA, and
DIR-A groups. The intensity of caspase 3 enzyme activity was significantly higher
in the I/R group than in all other groups. Inflammation and vascular dilatation
were found significantly higher in the DIR group than in all other groups.
Congestion was significantly higher in the DIR group than in the C and D groups.
TOS enzyme activity was significantly higher in the DIR group than in the C, DA
and DIR-A groups. TAS enzyme activity was significantly lower in the DIR group
than in the C and DIR-A groups. CONCLUSION: We believe that the protective
effects of apelin-13 in ischemia-reperfusion injury and its use indications can
be demonstrated in detail as long as the findings we have reached in our study
are supported by other studies (Tab. 2, Fig. 10, Ref. 43).
PMID- 29947235
TI - miRNA-31 over-expression improve synovial cells apoptosis induced by RA.
AB - OBJECTIVE: The aim of this study was to evaluate the effects and mechanism of
miRNA-31 in synovial cells apoptosis induced by RA. METHODS: The miRNA-31 gene
expressions were extracted from synovial tissues of normal and RA patients by RT
PCR and H et E staining. The synovial cells of RA patients were isolated and
randomly divided into Control, Blank and miRNA groups. The cell apoptosis of
difference groups were measured by flow cytometry; the TNF-alpha and IL-1beta
concentrations of difference groups were measured by Elisa assay; TLR4 and NF
kappaB proteins expressions were measured by WB assay and the correlation between
TLR4 and miRNA-31 were evaluated by double luciferase target experiment. RESULTS:
The miRNA-31 gene expression was significantly suppressed in RA tissues
(p<0.001); Compared with control group, the cell apoptosis rate of miRNA group
was significantly suppressed (p<0.001); TNF-alpha and IL-1beta concentrations
were significantly down-regulation in culture fluid (p<0.001, respectively) and
TLR4 and NF-kappaB proteins expressions were significantly depressed (p<0.001,
respectively) in miRNA group. By double luciferase target experiment, the TLR4
was a target gene of miRNA-31. CONCLUSION: miRNA-31 is a key role in synovial
cells apoptosis induced by RA (Fig. 7, Ref. 23).
PMID- 29947236
TI - Type 2 diabetes mellitus and thyroid disease: a two-sided analysis.
AB - AIM OF THE STUDY: To assess the prevalence of thyroid diseases in patients with
type 2 diabetes mellitus (T2DM) in comparison with normal population; to
determine prevalence of T2DM in patients with thyroid diseases. MATERIALS AND
METHODS: First group consisted of 60 patients with T2DM without previous history
of thyroid disease. Second group consisted of 60 patients with thyroid disease
without any previously known impairment of glucose metabolism. Control group (CG)
included 100 subjects who had no previous history of thyroid disease or glucose
metabolism impairment. Blood tests were performed to evaluate thyroid and glucose
metabolism parameters. RESULTS: We found a significantly higher prevalence of
thyroid diseases in patients with T2DM when compared to CG. Patients with T2DM
showed to have higher serum levels of free triiodothyronine (fT3), thyroid
stimulating hormone (TSH) and anti-thyroid peroxidase (anti-TPO) autoantibodies.
We found no statistical significance in prevalence of T2DM in patients with
thyroid diseases and CG. Among parameters of glucose metabolism, there were only
higher fasting glucose levels in patients with hyperthyroidism and autoimmune
thyroid disease (AITD). CONCLUSIONS: Patients with T2DM showed to have higher
prevalence of AITD and primary hypothyroidism. We did not find higher prevalence
of T2DM in patients with thyroid diseases (Tab. 3, Ref. 29).
PMID- 29947237
TI - Determination of CEBPA mutations by next generation sequencing in pediatric acute
leukemia.
AB - OBJECTIVES: The CCAAT/enhancer-binding protein-alpha (CEBPA) is lineage-specific
transcription factor in the hematopoietic system. In this study, we aimed on the
clinical features and the prognostic significance associated with CEBPA mutations
in 30 pediatric patients with acute leukemia. METHODS: In addition, the
association between found variants and mutations of Ten-Eleven-Translocation 2
(TET2), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Casitas B-cell
lymphoma (CBL), FLT3 (Fms-Related Tyrosine Kinase), JAK2 (Januse Kinase-2) and
Nucleophosmin 1 (NPM1) were analyzed, which are important prognostic risk factors
for pediatric acute leukemia patients. The entire CEBPA coding region was
screened using the NGS method. RESULTS: CEBPA mutations were detected in 16 (53.3
%) of 30 patients. In total, ten distinct of nucleotide changes were identified
in 30 patients, including 6 novel and 4 known mutations by sequencing the entire
CEBPA gene. We found 6 frame shift mutations, 1 missense mutation, 3 synonymous
variants. The most common mutation was the c.487del G resulting p.Glu163Ser in 5
cases. Three patients carried CEBPA double mutations. CONCLUSION: The detected
variants in this article seemed to be the first screening results of genes
studied by NGS in pediatric acute leukemia patients. Our results also showed some
degree of association between FLT3-ITD, TET2, KRAS, CBL and CEBPA mutations (Tab.
4, Fig. 1, Ref. 24).
PMID- 29947238
TI - Protective effects of intravenous lipid emulsion on malathion-induced
hepatotoxicity.
AB - OBJECTIVE: Organophosphates including malathion can be ingested, inhaled, or
absorbed through the skin, but it may be a maximum of acute toxicity when
administered by oral intake. Intravenous lipid emulsion (ILE) treatment is used
as a new treatment method in cases of systemic toxicity caused by local
anesthetics. This study was aimed to examine the potential treatment effect of
intravenous lipid emulsion on rat liver tissue in the toxicity of malathion.
METHODS: Twenty-one Wistar albino rats were randomly divided into three equal
groups. The groups were organized as Group I (control), Group II (malathion) and
Group III (malathion + lipid emulsion treatment). Liver tissues were examined
histologically, and immunohistochemical analysis was performed to determine the
bax, bcl-2, and caspase-3 expression levels. RESULTS: A decrease of PAS positive
staining cells, and an increase of liver enzymes, formation of degenerative
changes and apoptotic cell deaths occurred in the malathion group. Additionally,
a decrease of apoptosis and hepatic parenchymal damage was observed in the
malathion + lipid emulsion treatment group. CONCLUSION: The findings from our
study suggested that lipid emulsion treatment had a protective efficacy on the
malathion induced liver toxicity (Fig. 5, Ref. 30).
PMID- 29947239
TI - Manganese dioxide nanoparticle induces Parkinson like neurobehavioral
abnormalities in rats.
AB - AIM: Manganese dioxide magnetic nanoparticle (MnO2-NP) with specific size range
from 30 to 60 nm has widespread application in magnetic resonance imaging,
medicine and drug delivery in exposed humans and animals. Manganese nanoparticles
could affect hippocampus tissue and impose abnormal cognitive functions such as
manganese ion. Therefore, to investigate whether MnO2-NP is damaging hippocampus
tissue and inducing molecular and neurobehavioral abnormalities, we administrated
different doses of synthesized nanoparticle to rats and measured behavioral,
biochemical and histological parameters by standard methods. RESULTS: Results
showed that the treatment of rats with MnO2-NP during 15 days induced oxidative
stress and reduced catecholamine content in hippocampus tissue. MnO2-NP affected
hippocampus tissue appearance by increasing the number of apoptotic and necrotic
cells suggested that approved nanoparticle penetrated blood brain barrier and
reached the hippocampal cells. Interestingly, all biochemical and histological
effects of MnO2-NP were dose dependent. CONCLUSIONS: By considering that
hippocampus plays an important role in cognitive function, behavioral
abnormalities in intoxicated rats were predictable and nanoparticle administrated
rats showed depression like behavioral signs dose dependently. Based on our
results and previous studies that confirmed neurotoxicity of MnO2-NP in ug dose
rang, the application of this nanoparticles should be limited and their waste
should be neutralized before their release to the environment (Fig. 4, Ref. 31).
PMID- 29947240
TI - The impact of TFPI on coronary atherosclerotic burden.
AB - OBJECTIVES: We aimed to associate a coronary artery disease (CAD) presence and
severity with endothelial dysfunction (ED), carotid intima media thickness (CIMT)
and Tissue Factor Pathway Inhibitor (TFPI). BACKGROUND: ED has a central role in
atherosclerosis. CIMT and TFPI activity are also related with atherosclerosis and
CAD. METHODS: In our prospective observational study, 50 patients had CAD and 30
had normal coronary arteries. Endothelial function was evaluated by endothelium
dependent flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation
(NMD) measurements. CIMT and Serum TFPI levels were also measured. RESULTS: TFPI
was a statistically significant determinant between the two groups with an
increased level in CAD (+) group (84.9 +/- 19.3 vs 70.2 +/- 14.7, p = 0.001).
There was a positive correlation between CIMT and Gensini (r = 0.34, p = 0.014).
There was a strong negative correlation between Gensini and FMD-NMD,
statistically significant (FMD: r = -0.715, p < 0.001; NMD: r = -0.718, p <
0.001). CONCLUSION: We observed that ED, increased CIMT and TFPI levels were
associated with CAD. Additionally, increased CIMT measurements and decreased FMD
and NMD values had a positive correlation with GSS (Tab. 4, Fig. 6, Ref. 50).
PMID- 29947241
TI - The effect of synthetic alginate sulfate hydrogels with recombinant PDGF-BB on
Wound healing.
AB - OBJECTIVE: Platelet-derived growth factor (PDGF-BB) is an important factor in the
regeneration and wound healing. One of the problems is that there is not enough
efficiency in the transmission or delivery of such factors in the wound site. In
this study, alginate sulfate hydrogel was synthesized with recombinant PDGF-BB
growth factor for achieving a quick method in wound healing. METHODS: In this
study, Alginate sulfate hydrogel was made by photo-crosslinking method and
methacrylate. Its toxicity was evaluated by MTT assay. Transforming growth factor
was studied in releasing from synthesized alginate sulfate hydrogels and also,
lack of toxicity was confirmed, and hydrogel was made with a recombinant human
growth factor. Wounds were created with a diameter of 10 mm on the back of rats
in order to check the wound healing. RESULTS: This study showed that alginate
sulfate hydrogels-PDGF-BB were faster in wound healing than non-sulfate alginate
hydrogels-PDGF-BB. Therefore, the controlled delivery of growth factor system can
be a powerful idea for therapeutic applications for wound healing. CONCLUSION:
Alginate sulfate hydrogel with recombinant growth factor 4 ug/cm2 (PDGF-BB) was
very suitable for wound healing (Tab. 1, Fig. 3, Ref. 34).
PMID- 29947242
TI - A New HIV-1 Circulating Recombinant Form (CRF98_cpx) Between CRF06_cpx and
Subtype B Identified in Southwestern France.
AB - During a recent study on the sequencing data of our database between 2012 and
2016 in Southwestern France, we observed that eight patients harbored what seemed
to be the same virus. Indeed, routine genotyping at the time of HIV diagnosis
showed that protease and reverse transcriptase were related to CRF06_cpx and
subtype B, respectively. The integrase sequences (available for three patients)
were clustering with CRF06_cpx and envelope (Env) gp120 sequences (available for
two patients) with subtype B. Since such a recombinant has not been recorded in
the Los Alamos database, we decided to characterize the full-length genome of
this virus. The data suggest the identification of a new circulating recombinant
form (CRF) between CRF06_cpx and subtype B, the structure of which is very
complex with multiple breakpoints. We will refer this CRF as CRF98_cpx.
PMID- 29947243
TI - The Role of Endoscopic Sphenopalatine Ganglion Block on Nausea and Vomiting After
Sinus Surgery.
AB - Background Postoperative nausea and vomiting (PONV) are among the most common
unpleasant and distressing adverse events following surgery under general
anesthesia. Functional endoscopic sinus surgery (FESS) is a common otolaryngology
procedure. Prevention of PONV and early recovery are cost-effective. Objective
The aim of this study was to evaluate the prophylactic effect of bilateral
endoscopic injection of lidocaine with epinephrine in the sphenopalatine ganglion
(SPG) on PONV in patients undergoing FESS. Methods One hundred patients with
chronic rhinosinusitis undergoing general anesthesia for FESS were enrolled in
this double-blind, placebo-controlled study. Patients were randomized to receive
injection of 2 mL of 2% lidocaine with epinephrine or 2 mL of saline at the end
of surgery. Postoperatively, patients were observed for 24 h. PONV was evaluated
immediately, 6 h, and 24 h after surgery. Results The 2 groups were comparable in
characteristic and intraoperative features. In general, the incidence of PONV
after FESS was 36%. The average time that patients can tolerate oral feeding was
3.4 h after surgery. Endoscopic SPG injection with lidocaine significantly
reduced the incidence of vomiting and PONV. In addition, SPG injection with
lidocaine reduced the incidence of severe vomiting and decreased the number of
vomiting episodes. No complications were encountered in either group. Conclusion
SPG injection with lidocaine at the end of surgery is a safe, noninvasive, and an
effective technique in reducing early PONV in endoscopic sinus surgery patients.
PMID- 29947244
TI - Characteristics of Citrus Canker Lesions Associated with Premature Drop of Sweet
Orange Fruit.
AB - During the development of a citrus fruit, many cycles of infection by Xanthomonas
citri subsp. citri may occur leading to the development of a range of
characteristics of citrus canker lesions scattered across the fruit surface. This
study aimed to determine whether the size of the lesions, their distance from the
peduncle, and the number and time of appearance of the lesions on fruit of sweet
orange were associated with premature fruit drop. A multiple linear regression
analysis revealed a negative relationship between the fruit detachment force and
the lesion diameter, the proximity of the nearest lesion to the peduncle and the
number of lesions. A survival analysis demonstrated that these characteristics
significantly influenced the probability and the time that a cankered fruit
remained attached to the tree. More than 90% of dropped fruit had large lesions
(>5 mm) but not all fruit with large lesions dropped before harvest.
Approximately 50% of the harvested fruit had lesions >5 mm. On the harvested
fruit remaining on the tree, although large, the lesions had a smaller diameter,
were located farther from the peduncle, and were less numerous than those
observed on dropped fruit. Small canker lesions neither reduced the detachment
force nor the survival of fruit in the tree. The earlier a fruit expressed canker
symptoms, the higher the probability the fruit developed large lesions near the
peduncle and/or developed lesions in greater numbers. This study provides a
better understanding on the relationship between the time of appearance of
lesions of citrus canker on fruit and premature fruit drop. This information
defines the critical period for fruit protection and may be used to improve
disease management.
PMID- 29947245
TI - Emergence of Circulating Recombinant Form 56_cpx in Pakistan.
AB - In Pakistan, HIV has converted from outbreak to concentrated epidemic and has
also bridged into the low-risk population. The HIV epidemic in Pakistan mainly
comprises subtype A. Here, we present the first case and genetic analysis of a
circulating recombinant form 56_cpx in a Pakistani HIV-infected patient. Genetic
analysis of the sequence indicated that Pakistani 56_cpx sequence had more drug
resistance mutation than the other 56_cpx sequences available in the database.
PMID- 29947246
TI - Barriers to achieving the first 90%: gender norms and HIV testing among men in
the Democratic Republic of the Congo.
AB - Gender inequality and gender norms are key social drivers of the HIV epidemic
through their influences on sexual relationships, behavior, and risk taking.
However, few empirical studies have measured the influence of gender norms on HIV
sexual-risk behaviors and HIV testing among men in sub-Saharan Africa. We
analyzed cross-sectional, survey data from 399 sexually active men (ages 18-39)
in Democratic Republic of the Congo to examine the relationship between the men's
support for inequitable gender norms and their HIV-risk behaviors. Logistic
regression analyses revealed that moderate and strong levels of support for
inequitable gender norms were significantly associated with never having been
tested for HIV (AOR = 2.92, p < .05 and AOR = 3.41, p < .01, for moderate and
strong support, respectively). Our findings indicate that changing the prevailing
gender norms should be prioritized in HIV-prevention efforts that aim to increase
counseling and testing for men.
PMID- 29947248
TI - Corrigendum.
AB - Goldstein E, Topitzes J, Brown RL et al. (2018) Mediational pathways of
meditation and exercise on mental health and perceived stress: A randomized
controlled trial. Journal of Health Psychology. Epub ahead of print 7 May 2018.
DOI: 10.1177/1359105318772608.
PMID- 29947247
TI - Cardiovascular outcomes in patients who experienced a myocardial infarction while
treated with liraglutide versus placebo in the LEADER trial.
AB - OBJECTIVE: Animal studies demonstrated that glucagon-like peptide-1 receptor
agonists reduce myocardial necrosis following regional ischaemia induction. This
effect may improve cardiovascular outcomes after myocardial infarction. Risk of
cardiovascular death or hospitalisation for heart failure after myocardial
infarction was evaluated in patients with type 2 diabetes at high cardiovascular
risk in the LEADER trial. METHODS: Data from patients randomised to liraglutide
or placebo, in addition to standard of care, in Liraglutide Effect and Action in
Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) (NCT01179048)
were analysed post hoc. Cox regression, with myocardial infarction as a time
dependent covariate, was used to analyse time from randomisation to a composite
of cardiovascular death or hospitalisation for heart failure. RESULTS: Patients
who experienced myocardial infarction had a sevenfold higher risk of the
composite endpoint (with myocardial infarction: n = 148, 25.0%; without
myocardial infarction: n = 716, 8.2%; hazard ratio: 7.0; 95% confidence interval:
5.8, 8.4). The risk of the composite endpoint after myocardial infarction was not
significantly lower in the liraglutide group ( n = 63, 23.0%) compared with
placebo ( n = 85, 26.7%; hazard ratio: 0.91; 95% confidence interval: 0.66,
1.26). CONCLUSION: The data demonstrated that having myocardial infarction
significantly increased the risk of subsequent cardiovascular death or
hospitalisation for heart failure. However, we did not find evidence for a
reduced risk in these cardiovascular outcomes following myocardial infarction in
patients treated with liraglutide versus placebo.
PMID- 29947249
TI - Dual Combined Laparoscopic Approach for Renal-Cell Carcinoma with Renal Vein and
Level I-II Inferior Vena Cava Thrombus: Our Technique and Initial Results.
AB - OBJECTIVE: To present our technique and initial results of dual combined
retroperitoneal and transperitoneal laparoscopic approach for the treatment of
renal-cell carcinoma (RCC) with level 0-II venous tumor thrombus. PATIENTS AND
METHODS: We included nine consecutive patients with RCC and level 0-II inferior
vena cava (IVC) thrombus who underwent laparoscopic radical nephrectomy and IVC
thrombectomy using dual combined laparoscopic approach in our department between
January 2016 and June 2017. RESULTS: The mean operative time was 150 minutes when
cavotomy was not performed and 240 minutes when cavotomy with thrombectomy was
required. The mean IVC clamping time was 24 minutes and the mean blood loss was
300 mL. We encountered no major intraoperative or postoperative complications
(Clavien III-IV). The patients were discharged a mean of 7 days after the
procedure. At the 6-month follow-up, all patients were alive. One patient
presented a retroperitoneal enlarged lymph node and started systemic treatment.
CONCLUSIONS: The dual combined laparoscopic approach for kidney tumors with level
0-II IVC thrombus is feasible, reproducible, and especially useful in patients
with complex renal pedicle. The technique provides early arterial control by
retroperitoneal approach, which reduces the blood flow through the renal vein and
has the advantage of minimal mobilization of the thrombus-bearing renal vein; it
therefore lowers the risk of tumor embolism and intraoperative hemorrhage.
PMID- 29947250
TI - Two new naphthalene glycosides from the seeds of Cassia obtusifolia.
AB - A phytochemical study on the seeds of Cassia obtusifolia was carried out, which
finally led to obtain two naphthalenes (1 and 2), two naphthopyrans (3 and 4) and
twelve anthraquinones (5-16). The structures of all compounds were established
mainly by NMR and MS experiments as well as the necessary chemical evidence.
Among them, 1 and 2 (obtusinaphthalensides A and B) were identified to be new
naphthalene glycosides.
PMID- 29947251
TI - Racial/ethnic minority segregation and low birth weight in five North American
cities.
AB - Comparisons of communities across cities are rare in social epidemiology. Our
prior work exploring racial/ethnic segregation and the prevalence of low birth
weight (LBW) in communities from two large urban cities showed a strong
relationship in Chicago and a very weak relationship in Toronto. This study
extends that work by examining the association between racial/ethnic minority
segregation and LBW in total of 307 communities in five North American cities:
Baltimore, Boston, Chicago, Philadelphia, and Toronto. We used Pearson
correlation coefficients and OLS regression models to examine potential
variability in the association between racial/ethnic minority segregation and
LBW, controlling for community-level unemployment. In a combined model with
community-level data from all cities, a 10% increase in minority composition is
associated with a 0.7% increase in LBW. While racial/ethnic minority segregation
and unemployment are not associated with LBW in Toronto, these social
determinants have strong and significant associations with LBW across communities
in the four US cities in the analysis. Subsequent models revealed opposite
effects for percentage non-Hispanic Black and percentage Hispanic. Across
communities in the US cities in this analysis, there is considerable similarity
in the strength of the effect of racial/ethnic segregation on LBW. Future work
should incorporate communities from additional cities, looking to identify
community assets and public policies that allow some minority communities to
thrive, while other minority communities suffer from a high prevalence of LBW.
More work is also needed on the generalizability of these patterns to other
health outcomes.
PMID- 29947253
TI - Three-dimensional radiological evaluation of secondary alveolar bone grafting in
cleft lip and palate patients: a systematic review.
AB - OBJECTIVES: To systematically review the existing literature on the three
dimensional (3D) radiological evaluation of secondary alveolar bone grafting
(SABG) in cleft lip and palate (CLP) patients, with specific interest in 3D
imaging protocols and assessment methods. Methods: A comprehensive literature
search on PubMed, Embase and the Cochrane Library was conducted. Included
publications concerned 3D imaging for evaluation of SABG in CLP patients while
articles about primary or tertiary bone grafting or using of two-dimensional
images only were excluded. Study quality was evaluated using the Methodological
Index for Non-Randomized Studies or the Cochrane Collaboration tool for
assessing risk of bias. RESULTS: The search yielded 1735 citations, of which 38
met the inclusion criteria. We noticed a large variability in imaging protocols
and bone graft evaluation methods between studies. Most articles were
observational studies with medium to low methodological quality, except for the
one randomised clinical trial having a low risk of bias. Conclusions: There is a
lack of prospective, controlled trials based on a consistent imaging protocol
with a sufficiently long follow-up period. A pressing need exists for the
development of a consistent optimized imaging protocol for diagnosis and follow
up of SABG in CLP patients. Although 3D evaluation methods seem to be more
precise than two-dimensional methods, we should be careful when comparing the
outcomes arising from different 3D measuring techniques.
PMID- 29947252
TI - The impact of in vitro cell culture duration on the maturation of human
cardiomyocytes derived from induced pluripotent stem cells of myogenic origin.
AB - Ischemic heart disease, also known as coronary artery disease (CAD), poses a
challenge for regenerative medicine. iPSC technology might lead to a breakthrough
due to the possibility of directed cell differentiation delivering a new powerful
source of human autologous cardiomyocytes. One of the factors supporting proper
cell maturation is in vitro culture duration. In this study, primary human
skeletal muscle myoblasts were selected as a myogenic cell type reservoir for
genetic iPSC reprogramming. Skeletal muscle myoblasts have similar ontogeny
embryogenetic pathways (myoblasts vs. cardiomyocytes), and thus, a greater chance
of myocardial development might be expected, with maintenance of acquired
myogenic cardiac cell characteristics, from the differentiation process when
iPSCs of myoblastoid origin are obtained. Analyses of cell morphological and
structural changes, gene expression (cardiac markers), and functional tests
(intracellular calcium transients) performed at two in vitro culture time points
spanning the early stages of cardiac development (day 20 versus 40 of cell in
vitro culture) confirmed the ability of the obtained myogenic cells to acquire
adult features of differentiated cardiomyocytes. Prolonged 40-day iPSC-derived
cardiomyocytes (iPSC-CMs) revealed progressive cellular hypertrophy; a better
developed contractile apparatus; expression of marker genes similar to human
myocardial ventricular cells, including a statistically significant CX43
increase, an MHC isoform switch, and a troponin I isoform transition; more
efficient intercellular calcium handling; and a stronger response to beta
adrenergic stimulation.
PMID- 29947254
TI - Daily management of attention dysfunction two-four years after brain injury and
early cognitive rehabilitation with attention process training: a qualitative
study.
AB - The evaluation of intensive cognitive training is usually based on
neuropsychological tests and questionnaires. A study of the subjective experience
of cognitive training would provide another type of valuable information
concerning the effects of rehabilitation. We used grounded theory methods to
explore the experience and management of attention dysfunction in daily life two
four years after brain injury. Data were collected by in-depth interviews of 14
adults with moderate-to-mild attention dysfunction after stroke or traumatic
brain injury, and working part time or full time at the time of the interviews.
The group received 20 hours of attention process training within the context of
multidisciplinary rehabilitation early after brain injury. Data were analysed by
open coding with constant comparison. The management of attention dysfunction was
described by the informants as a dynamic process where strategies are
continuously refined and flexibly adjusted as awareness and metacognitive
knowledge increases. This process is regulated by situation-dependent factors.
Attention process training might provide a suitable starting point for the
identification of problem areas, improved specific goalsetting and stimulated
self-training. The model describes the dynamic nature of the process, the ongoing
struggle, self-training and search for feedback.
PMID- 29947255
TI - Adiponectin Attenuates Oxygen-Glucose Deprivation-Induced Mitochondrial Oxidative
Injury and Apoptosis in Hippocampal HT22 Cells via the JAK2/STAT3 Pathway.
AB - Ischemic stroke is among the leading causes of morbidity and mortality worldwide.
Improving the tolerance of neurons to ischemia and reperfusion injury could be a
feasible strategy against ischemia. Adiponectin (APN) is a major adipokine that
regulates glucose and lipid metabolism and plays an important role in the
protection of the cerebral nervous system. We aimed to investigate the effects of
APN on oxygen and glucose deprivation (OGD)-induced neuronal injury in
hippocampal neuronal HT22 cells. APN displayed neuroprotective effects against
OGD, evidenced by increased cell viability and decreased lactate dehydrogenase
release and apoptotic rate. Additionally, APN also maintained mitochondrial
ultrastructure and transmembrane potential, attenuated reactive oxygen species
and malondialdehyde, and increased superoxide dismutase and glutathione
peroxidase activity. Moreover, APN promoted Janus kinase 2 (JAK2)/signal
transducer and activator of transcription 3 (STAT3) phosphorylation, enhanced
STAT3 nuclear translocation, increased the Bcl-2/Bax ratio, and decreased cleaved
caspase-3. The aforementioned APN-induced effects were almost reversed by a JAK2
inhibitor, AG490. APN may attenuate OGD-induced hippocampal HT22 neuronal
impairment by protecting cells against mitochondrial oxidative stress and
apoptosis, mediated by JAK2/STAT3 signaling.
PMID- 29947257
TI - Cucumol B, a new triterpene benzoate from Cucumis melo seeds with cytotoxic
effect toward ovarian and human breast adenocarcinoma.
AB - Phytochemical investigation of the methanolic extract of Cucumis melo L.
(Cucurbitaceae) seeds furnished a new triterpene benzoate derivative: cucumol B
(1) and four known flavonoids: quercetin-3-O-beta-D-glucopyranosyl-(1->6)-alpha-L
rhamnopyranoside (2), quercetin-3-O-beta-D-glucopyranoside (3), quercetin (4),
and luteolin (5). Their structures were identified by UV, IR, 1D (13C and 1H), 2D
(HSQC, 1H-1H COSY, HMBC, and NOESY) NMR, and HRESIMS spectral as well as
comparing with literature data. Compound 1 has been assessed for the in vitro
cytotoxic effect against SKOV-3, MCF-7, and HCT-116 cell lines. It had selective
and potent effect toward SKOV-3 and MCF-7 cell lines with IC50s 2.05 and 0.41
MUM, respectively, in comparison to doxorubicin (IC50s 0.32 and 0.05 MUM).
However, it showed moderate activity toward HCT-116 cell line with IC50 8.27 MUM.
PMID- 29947256
TI - Comparison of Mesenchymal Stromal Cells Isolated from Murine Adipose Tissue and
Bone Marrow in the Treatment of Spinal Cord Injury.
AB - The use of mesenchymal stromal cell (MSC) transplantation to repair the injured
spinal cord has shown consistent benefits in preclinical models. However, the low
survival rate of grafted MSC is one of the most important problems. In the
injured spinal cord, transplanted cells are exposed to hypoxic conditions and
exposed to nutritional deficiency caused by poor vascular supply. Also, the
transplanted MSCs face cytotoxic stressors that cause cell death. The aim of this
study was to compare adipose-derived MSCs (AD-MSCs) and bone marrow-derived MSCs
(BM-MSCs) isolated from individual C57BL6/J mice in relation to: (i) cellular
characteristics, (ii) tolerance to hypoxia, oxidative stress and serum-free
conditions, and (iii) cellular survival rates after transplantation. AD-MSCs and
BM-MSCs exhibited a similar cell surface marker profile, but expressed different
levels of growth factors and cytokines. To research their relative stress
tolerance, both types of stromal cells were incubated at 20.5% O2 or 1.0% O2 for
7 days. Results showed that AD-MSCs were more proliferative with greater culture
viability under these hypoxic conditions than BM-MSCs. The MSCs were also
incubated under H2O2-induced oxidative stress and in serum-free culture medium to
induce stress. AD-MSCs were better able to tolerate these stress conditions than
BM-MSCs; similarly when transplanted into the spinal cord injury region in vivo,
AD-MSCs demonstrated a higher survival rate post transplantation Furthermore,
this increased AD-MSC survival post transplantation was associated with
preservation of axons and enhanced vascularization, as delineated by increases in
anti-gamma isotype of protein kinase C and CD31 immunoreactivity, compared with
the BM-MSC transplanted group. Hence, our results indicate that AD-MSCs are an
attractive alternative to BM-MSCs for the treatment of severe spinal cord injury.
However, it should be noted that the motor function was equally improved
following moderate spinal cord injury in both groups, but with no significant
improvement seen unfortunately following severe spinal cord injury in either
group.
PMID- 29947258
TI - A new medermycin analog from the marine-derived actinomycetes Streptomyces sp. ZS
A45.
AB - A new medermycin analog (1) was isolated from the marine-derived actinomycetes
Streptomyces sp. ZS-A45. The structure elucidation of compound 1 was determined
by the HRESIMS and extensive NMR analysis. And compound 1 exhibited significant
cytotoxicity against PC3 cell lines with IC50 values of 0.81 +/- 0.42 MUm.
PMID- 29947259
TI - Acanthiline A, a pyrido[1,2-a]indole alkaloid from Chinese mangrove Acanthus
ilicifolius.
AB - Chemical investigation of the leaves and stems of the Chinese mangrove Acanthus
ilicifolius Linn. led to the isolation and structure elucidation of one new
pyrido[1,2-a]indole alkaloid named acanthiline A (1), together with one known
compound aurantiamide acetate (2). Compound 1 has a previously unreported natural
product skeleton. The structure elucidation of 1 was based on the analysis of its
1D and 2D NMR and mass spectroscopic data.
PMID- 29947260
TI - Outcomes and Complications of Balloon and Conventional Functional Endoscopic
Sinus Surgery.
AB - Background Since the Food and Drug Administration approval of balloon sinuplasty
(BSP) in 2005, no nationally representative population-based studies have
examined the outcomes and adverse events of BSP. Objective To assess the rates of
complications and revision surgery in patients who received BSP, functional
endoscopic sinus surgery (FESS), or a hybrid procedure. Methods Using one of the
nation's largest commercial insurance databases, we conducted a retrospective
cohort study of pediatric and adult patients diagnosed with chronic
rhinosinusitis between 2011 and 2014 who underwent BSP, conventional FESS, or a
hybrid procedure. The primary outcomes were surgical complication and revision
rates within 6 months of initial surgery. Results A total of 16,040 patients who
underwent sinus surgery were included. Overall, 2,851 patients underwent BSP,
11,955 underwent conventional FESS, and 1 234 underwent a hybrid procedure. BSP
surgery was more likely to have been performed in an office setting (86.53%)
compared to FESS (0.74%). The complication rate was 5.26% for BSP and 7.35% for
conventional FESS. Revision rates were 7.89% for BSP, 16.85% for FESS, and 15.15%
for a hybrid procedure. Conclusion Despite the low overall risk, major
complications occur with BSP including cerebrospinal fluid leak, pneumocephalus,
orbital complications, and severe bleeding. Otolaryngologists should discuss
these risks with their patients. Prospective studies are still needed to compare
outcomes of BSP with those of FESS.
PMID- 29947261
TI - Cellular Subsets of Maternal Microchimerism in Umbilical Cord Blood.
AB - Maternal microchimerism may arise in the offspring during pregnancy, and may be
favorable or unfavorable. Additionally, maternal cells present in umbilical cord
blood used for stem cell transplantation may affect the outcome after
transplantation. The aim of this study was to evaluate the cellular subset and
frequency of maternal cells in umbilical cord blood following vaginal deliveries
and elective Cesarean sections where the umbilical cord clamping time was
measured. A total of 44 healthy women with normal pregnancies were included in
the study. Of these, 24 delivered vaginally and 20 by elective Cesarean sections.
In the fresh umbilical cord blood, cellular subsets of CD3+ (T-cells), CD19+ (B
cells), CD33+ (myeloid cells), CD34+ (hematopoietic progenitor cells) and CD56+
(natural killer cells) cells were isolated and DNA extracted. A single-nucleotide
polymorphism unique to the mother was identified and maternal microchimerism in
the different cellular fractions was detected using quantitative real-time
polymerase chain reaction with a sensitivity of 0.01%. Overall, 5 out of the 44
(11%) umbilical cord blood samples contained maternal microchimerism. The
positive fractions were total DNA (whole blood, n = 3), CD34+ ( n = 1), CD56+ ( n
= 1) and CD34+/CD56+ ( n = 1). Overall, four of the five (80%) positive samples
were from Cesarean sections and one was from a vaginal delivery. The conclusion
from this study is that maternal microchimerism in umbilical cord blood is not a
common phenomenon but includes both lymphoid and hematopoietic progenitor
lineages.
PMID- 29947262
TI - In vitro effects of some antibiotics on glucose-6-phosphate dehydrogenase from
rat (Rattus norvegicus) erythrocyte.
AB - Glucose-6-phosphate dehydrogenase (G6PD) plays a key function in various
biochemical processes as they produce reducing power of the cell. Thus, metabolic
reprogramming of nicotinamide adenine dinucleotide homeostasis is reported to be
an important step in cancer progression as well as in combinational therapeutic
approaches. In this study, the effects of the antibiotics, furosemide, cefazolin,
cefuroxime, gentamicin and clindamycin on rat erythrocyte G6PD enzyme was studied
in in vitro conditions. The enzyme was purified by 2', 5'-adenosine diphosphate
Sepharose 4B affinity chromatography in a single purification step with 1825 fold
and 83.7% yield. The specific activity of the enzyme was 29.2 EU/mg proteins. The
inhibition studies of these antibiotics were carried out on the enzyme revealing
that gentamicin, clindamycin and furosemide inhibited the activity of the G6PD
with an IC50 of 1.75, 34.65 and 0.526 mM, respectively with Ki of 0.7, 39.8 and
0.860 mM, respectively. All inhibition types were analyzed by Lineweaver-Burk
diagram showing noncompetitive inhibition for furosemide and gentamicin while
clindamycin inhibited the activity competitively. On the other hand, cefazolin
and cefuroxime increased the activity of the enzyme.
PMID- 29947263
TI - Two new compounds from the roots of Swietenia macrophylla.
AB - Phytochemical investigation on the roots of Swietenia macrophylla yielded one new
pharagmalin-type limonoid named 2-dehydroxyl-swietephragmin C (1) and one new
xanthone, 1,5-dihydroxy-6-methoxy-6',6'-dimethyl-2H-pyrano[2',3':3,2]xanthone
(2), in addition to three known compounds. The structures of the new compounds
were unambiguously determined by comprehensive spectroscopic methods (NMR, UV,
IR, MS), as well as by comparison with the reported data in the literature.
Xanthones were reported from Swietenia genus for the first time.
PMID- 29947264
TI - The use of new delineation tool "MIRADA" at the level of regional lymph nodes,
step-by-step development and first results for early-stage breast cancer
patients.
AB - OBJECTIVE:: To describe the practical procedure of implementation and
optimization of delineation using "Mirada" software, as well as evaluation of the
automatic segmentation for the daily practice of lymph nodes (LN) and organs at
risk (OARs) in early stage breast cancer patients. METHODS:: 40 patients' CT
scans in treatment position were selected and recontoured according to the
European Society of Therapeutic Radiation Oncology guidelines. The atlas of data
set was then created for automatic delineation. 30 patients with breast/chest
wall and lymph nodes regions irradiated were recruited for evaluation. With the
same treatment position, the CT scan images were acquired and then contoured by
the MIRADA system automatically as well as by the radiation oncologist manually
(as the reference). The conformity index (CI) was used to evaluate the
concordance between both of them. RESULTS:: The mean time for manual contour was
24.1 +/- 5.1 and 26.4 +/- 2.8 min for the LN and the OARs respectively. All the
volumes of interest were contoured using the software (including corrections) in
30 min, which reduced the time of delineation of target volumes and OAR by about
40%. Of the 30 cases evaluated, the mean CI of 5 principal OARs showed >=0.8.
While the automatic contour of LN was less satisfactory with mean CI of 0.43 +/-
0.1 (0.23-0.52). CONCLUSION:: For the breast cancer patients, the studied
software permitted to save time for delineation with acceptable OAR contours. The
improvement of LN regions contour is needed. More cases and further evaluation
are needed for the system to realize its routine use. ADVANCES IN KNOWLEDGE::
It's the first description and evaluation of the automatic delineation and
segmentation system for the breast cancer.
PMID- 29947265
TI - High risk breast lesions identified on MRI-guided vacuum-assisted needle biopsy:
outcome of surgical excision and imaging follow-up.
AB - OBJECTIVE:: To determine whether breast MRI-guided vacuum-assisted biopsy (MRI
VAB) high-risk lesion histology influences surgical or long-term imaging follow
up outcomes. METHODS:: Patients with imaging-concordant high-risk findings on 9
gauge breast MRI-VAB between January 2007 and July 2012 who had surgical
histopathology or 2 year imaging follow-up were retrospectively reviewed.
RESULTS:: 90 patients with 99 lesions were included. Lesions were atypical ductal
hyperplasia (ADH) (n = 21), lobular neoplasia [n = 36; atypical lobular
hyperplasia (ALH) (n = 22), lobular carcinoma in situ (LCIS) (n = 6), and ALH
plus LCIS (n = 8)], and other high-risk lesion (n = 42; papillary lesions, radial
scar, flat epithelial atypia, atypia unspecified). Of 53 excised lesions, 6 (11%)
were upgraded to invasive cancer or ductal carcinoma in situ (DCIS). 4 of 21
(19%) ADH lesions were upgraded to DCIS. 2 of 36 (6%) lobular neoplasia lesions,
both combined ALH and LCIS, were upgraded to DCIS, and invasive lobular
carcinoma, respectively. The remaining 46 lesions were managed conservatively
with imaging follow-up: 17 (37%) had mammography only, while 29 (63%) had
mammography and MRI follow-up. There was no evidence of breast cancer development
at the site of MRI-VAB in the cases with only imaging follow-up. CONCLUSION:: We
conclude that the upgrade rate for high-risk lesions at MRI-VAB at surgical
excision is low. Surgical excision is warranted for ADH and combined ALH-LCIS
lesions. For other lesions, a multidisciplinary approach to decide on
personalized management may be appropriate. ADVANCES IN KNOWLEDGE:: Surgical
excision is warranted for ADH lesions and combined ALH-LCIS lesions identified at
breast MRI-VAB. A multidisciplinary approach to patient management of other high
risk lesions may be appropriate.
PMID- 29947266
TI - A review on radiomics and the future of theranostics for patient selection in
precision medicine.
AB - The growing complexity and volume of clinical data and the associated decision
making processes in oncology promote the advent of precision medicine. Precision
(or personalised) medicine describes preventive and/or treatment procedures that
take individual patient variability into account when proscribing treatment, and
has been hindered in the past by the strict requirements of accurate, robust,
repeatable and preferably non-invasive biomarkers to stratify both the patient
and the disease. In oncology, tumour subtypes are traditionally measured through
repeated invasive biopsies, which are taxing for the patient and are cost and
labour intensive. Quantitative analysis of routine clinical imaging provides an
opportunity to capture tumour heterogeneity non-invasively, cost-effectively and
on large scale. In current clinical practice radiological images are
qualitatively analysed by expert radiologists whose interpretation is known to
suffer from inter- and intra-operator variability. Radiomics, the high-throughput
mining of image features from medical images, provides a quantitative and robust
method to assess tumour heterogeneity, and radiomics-based signatures provide a
powerful tool for precision medicine in cancer treatment. This study aims to
provide an overview of the current state of radiomics as a precision medicine
decision support tool. We first provide an overview of the requirements and
challenges radiomics currently faces in being incorporated as a tool for
precision medicine, followed by an outline of radiomics' current applications in
the treatment of various types of cancer. We finish with a discussion of possible
future advances that can further develop radiomics as a precision medicine tool.
PMID- 29947267
TI - Automatic contrast medium extraction system using electron density data with dual
energy CT.
AB - OBJECTIVE:: The purpose of the current study is to create a contrast medium
extraction method using raw-data-based electron density (rED) and CT number from
dual-energy CT (DECT) for automatic delineation of the contrast region. METHODS::
A CT-ED phantom containing tissue-equivalent inserts and an acrylic phantom with
an iodinated contrast medium were scanned by DECT. The contrast medium extraction
system was created using Python. The accuracy of the contrast medium extraction
was evaluated by measuring the diameter in terms of the full width at half
maximum (FWHM) and the ratio of the volume (ROV). RESULTS:: Mean-2SD CT numbers
and the difference of the CT numbers (DCT) of the contrast medium at 0-130 mg ml
1 contrast medium concentration and the bone materials were more than -33 and -20
HU, respectively. In the correlation of rED and CT number, the gradient with the
contrast medium phantom was greater than that with the CT-ED phantom. The
accuracy of the contrast medium at 80 kV/135 kV and 100 kV/135 kV tube voltages.
The gradient of the CT-ED and contrast medium phantoms were different. The
gradient in the CT-ED phantom and the contrast medium was 0.0012 and 0.0003 at 80
kV/135 kV, and 0.0015 and 0.0005 at 100 kV/135 kV tube voltages, respectively.
The ratio of the measured to the actual diameter in FWHM and ROV was 0.98-1.00 at
2-130 mg ml-1. At a tube voltage of 100 kV/135 kV. The ratio of the measured to
the actual diameter in ROV was 0.66 and FWHM was 0.90 at 2 mg ml-1 contrast
medium concentration. The ratio of the measured to the actual diameter in FWHM
and ROV was 0.98-1.00 at 3-130 mg ml-1. CONCLUSION:: We created the contrast
medium extraction method with rED and CT number images. The contrast medium
extraction method could be used with DECT images at 80 kV/135 kV. The method is
expected to only extract images from the region containing the contrast medium.
ADVANCES IN KNOWLEDGE:: We created the contrast medium extraction method using
raw-data-based electron density and CT number from DECT and it is expected to
only extract information from the region containing the contrast medium.
PMID- 29947268
TI - Imaging of inguinal-related groin pain in athletes.
AB - Inguinal canal-related groin pain is common in athletes and may involve numerous
structures such as the conjoint tendon and the transversalis fascia. Ultrasound
is the only dynamic tool that shows the passage of preperitoneal fat at the level
of the Hesselbach triangle and allows excluding true inguinal hernias. Fascia
transversalis bulging and inguinal ring dilatation may also be described. MRI
assesses injuries of rectus abdominis and adductor longus enthesis and osteitis
symphysis but its accuracy for the diagnosis of inguinal-related groin pain
remains debated.
PMID- 29947269
TI - Infant of diabetic mother: what one needs to know?
AB - The global incidence of diabetes mellitus, including diabetes in pregnant women,
is on the rise. Diabetes mellitus in a pregnant woman jeopardizes not only
maternal health but can also have significant implications on the child to be
born. Therefore, timely diagnosis and strict glycemic control are of utmost
importance in achieving a safe outcome for both the mother and fetus. The
treating physician should be aware of the complications that can arise due to
poor glycemic control during pregnancy. The objective of this article is to
discuss the key concerns in a neonate born to diabetic mother, the underlying
pathogenesis, and the screening schedule during pregnancy.
PMID- 29947270
TI - Induction of cross-tolerance between protective effect of morphine and nicotine
in 6-hydroxydopamine-induce neurotoxicity in SH-SY5Y human dopaminergic
neuroblastoma cells.
AB - PURPOSE: Parkinson's disease is a progressive neurodegenerative disease
characterized by progressive and selective death of dopaminergic neurons. It has
been reported that nicotine and morphine have protective roles during neuronal
damage in Parkinson's disease. In addition, the induction of cross-tolerance
between their biological effects has been shown in numerous reports. METHODS:
Here, we investigated the effects of nicotine and morphine on 6-OHDA-induced
neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of
Parkinson's disease. Cell damage was induced by 150 MUM 6-OHDA and the cells
viability was examined by MTT assay. Intracellular reactive oxygen species,
calcium level, and mitochondrial membrane potential were determined by
fluorescence spectrophotometer method. Biochemical markers of apoptosis were also
evaluated by immunoblotting. RESULT: The data showed that morphine and nicotine
prevent 6-OHDA- induced cell damage and apoptosis. However, the protective
effects of nicotine were not observed in chronic morphine-pretreated cells.
Morphine had no protective effects in chronic nicotine-incubated cells.
CONCLUSION: A cross-tolerance between protective effects of morphine and nicotine
was occurred in 6-OHDA-induced SH-SY5Y cell toxicity.
PMID- 29947271
TI - Elevating the use of sugar-free chewing gum in Germany: cost saving and caries
prevention.
AB - OBJECTIVE: To analyse the lifetime monetary and health related effects of the
consumption of sugar-free chewing gum. MATERIAL AND METHODS: Using a Markov model
we assumed that the German consumption of sugar-free chewing gum (111 gums/year)
could be elevated to the level of Finland (202 gums/year). The calculation was
based on a model patient representing the development of oral health from the age
of 12 to 74 years and clinical data on the effectiveness of chewing sugar-free
gum. Lifetime and yearly costs for the 'Finland-scenario' were determined and
compared with the actual German expenses of the statutory health insurance
companies for dental health. RESULTS: The actual total lifetime expenditures of
the statutory health insurance companies are 17,199.96? per capita and would be
12,188.94? in the scenario with elevated consumption of sugar-free chewing gum in
Germany. Thus, 5011.02? per capita could be saved in a lifetime and 80.82? per
year. CONCLUSIONS: On a national scale, the elevation of the consumption of sugar
free chewing gum in Germany to the level of Finland would lead to a considerable
benefit for cost saving and oral health for the statutory health insurance
companies.
PMID- 29947272
TI - Role of Endogenous and Exogenous Corticosterone on Behavioral and Cognitive
Responses to Low-Pressure Blast Wave Exposure.
AB - The complex interactions and overlapping symptoms of comorbid post-traumatic
stress disorder (PTSD) and mild traumatic brain injury (mTBI) induced by an
explosive blast wave have become a focus of attention in recent years, making
clinical distinction and effective intervention difficult. Because dysregulation
of the hypothalamic-pituitary-adrenal (HPA) axis is thought to underlie trauma
related (psycho)pathology, we evaluated both the endogenous corticosterone
response and the efficacy of exogenous hydrocortisone treatment provided shortly
after blast exposure. We employed a controlled experimental blast-wave paradigm
in which unanesthetized animals were exposed to visual, auditory, olfactory, and
tactile effects of an explosive blast wave produced by exploding a thin copper
wire. Endogenous corticosterone concentrations were evaluated at different time
points (before, and 3 h, 5 h and 17 days) after blast exposure. Subsequently, the
efficacy of exogenous hydrocortisone (25 mg/kg-1 or 125 mg/kg-1) injected
intraperitoneally 1 h after exposure was compared with that of a similarly timed
saline injection. Validated cognitive and behavioral tests were used to assess
both PTSD and mTBI phenotypes on days 7-14 following the blast. Retrospective
analysis revealed that animals demonstrating the PTSD phenotype exhibited a
significantly blunted endogenous corticosterone response to the blast compared
with all other groups. Moreover, a single 125 mg/kg-1 dose of hydrocortisone
administered 1 h after exposure significantly reduced the occurrence of the PTSD
phenotype. Hydrocortisone treatment did not have a similar effect on the mTBI
phenotype. Results of this study indicate that an inadequate corticosteroid
response following blast exposure increases risk for PTSD phenotype, and
corticosteroid treatment is a potential clinical intervention for attenuating
PTSD. The differences in patterns of physiological and therapeutic response
between PTSD and mTBI phenotypes lend credence to the retrospective behavioral
and cognitive classification criteria we designed, and is in keeping with the
assumption that mTBI and PTSD phenotypes may reflect distinct underlying
biological and clinical profiles.
PMID- 29947273
TI - Pathways to care among psychiatric outpatients in a tertiary mental health
institution in Singapore.
AB - BACKGROUND: Pathways to care studies in Singapore are of high interest given the
cultural diversity and various sources of help available for those with mental
illnesses, ranging from the more traditional to tertiary-level mental health care
services. AIM: The current study aimed to explore the associations of patients'
socio-demographic characteristics with pathways to first contact and duration of
untreated mental illness. METHOD: A total of 402 participants were recruited
through convenience sampling. A pathway to care form was used to gather
systematic information about the sources of care utilized by participants before
approaching a mental health professional. Data were analysed using multinomial
logistic regression and multiple linear regression models to assess the
associations. RESULTS: Majority of participants reported primary care (36.0%) as
their first point of contact, followed by non-formal sources of help (33.8%),
specialist care (21.8%), police/court (4.0%), websites/media (3.3%) and
religious/traditional treatment (1.3%). Those belonging to Malay and Indian
ethnicity (vs Chinese) were more likely to make first contact with non-formal
sources of help than primary care. Those who received a diagnosis of any mood or
anxiety disorder (vs schizophrenia and related psychoses) were less likely to
make first contact with specialist care or non-formal sources of help than
primary care. Those who were separated/divorced/widowed were significantly
associated with higher duration of untreated illness compared to those who were
single. Participants whose family/relative initiated the first contact were
significantly associated with a shorter duration of untreated illness compared to
those who initiated first contact on their own. CONCLUSION: Findings suggest the
determinants of the pathways to first contact and duration of untreated illness
included diagnosis, ethnicity, marital status and family initiating the first
contact. The pathways adopted by these participants need to be kept in mind for
planning mental health programmes.
PMID- 29947274
TI - Re-arthrodesis after primary ankle fusion: 134/1,716 cases from the Swedish Ankle
Registry.
AB - Background and purpose - Arthrodesis is the most common treatment of severe ankle
arthritis. Large studies on the occurrence of re-arthrodesis are few, especially
with information in terms of risk. We used the National Swedish Ankle Registry to
assess incidence and risk factors for re-arthrodesis. Patients and methods - In
the Registry, we examined the occurrence of re-arthrodesis in 1,716 patients with
a primary ankle arthrodesis. We also analyzed associations between the re
arthrodesis risk and sex, diagnosis, and surgical method. Results - The risk of
first re-arthrodesis at 2.5 years was 7.4% and the rate at 9 years 7.8%. The risk
following arthroscopic surgery with fixation by screws was 15%, which is
statistically significantly higher than the 8% following the gold standard
technique with open screw fixation, the 5% following fixation by intramedullary
nailing, and the 3% following fixation by plate and screws. Patients with either
idiopathic osteoarthritis or posttraumatic arthritis had a higher risk of re
arthrodesis than patients with rheumatoid arthritis. We could not find that the
risk of re-arthrodesis was associated with sex. Interpretation - In Sweden, the
re-arthrodesis risk varied by primary technique and was especially high after
arthroscopic surgery. Reasons are unknown but poor surgical technique and/or
surgeon inexperience may contribute, as may patient selection.
PMID- 29947275
TI - Systemic lupus erythematosus: nothing stale her infinite variety.
AB - Systemic lupus erythematosus (SLE) is a representative systemic autoimmune
disease that has various types of manifestations in multiple organs.
Additionally, SLE is one of the most variable diseases in its epidemiology and
etiology with heterogenous types of immune dysfunction. Since the word 'lupus'
has first appeared in the literature in the Middle Ages, clinical/pathological
knowledges have massively accumulated that contributed to the establishments and
improvements of classification criteria, therapeutic agents or assessments of
disease activity. Along with them, the survival rate of patients with SLE has
dramatically improved. However, the mortality rate is still higher compared with
the healthy population and the progress in basic, translational and clinical
research are expected to lead to new insights into pathogenesis and identifying
novel targets for therapy.
PMID- 29947277
TI - Cationic polystyrene nanoparticle and the sea urchin immune system: biocorona
formation, cell toxicity, and multixenobiotic resistance phenotype.
AB - In order to assess the impact of nanoplastics on marine species, polystyrene
nanoparticles (PS NPs) have been largely used as model particles. Here we studied
the effects of 50 nm amino-modified PS-NH2 on Mediterranean sea urchin
Paracentrotus lividus immune system cells (coelomocytes) in the presence of
celomic fluid (CF) and at different NP concentrations (1, 5, 10, and 25 MUg mL-1)
and experimental conditions (absence or presence of EDTA). PS-NH2 acquired a
protein corona once incubated with CF, dominated by the toposome precursor
protein (TPP). In short-term cultures, a significant concentration- and time
dependent decrease in lysosomal membrane stability and apoptotic-like nuclear
alterations were observed in phagocytes upon exposure to PS-NH2 (10 and 25 ug mL
1) in CF but they resulted abolished in the presence of EDTA confirming the role
of TPP in triggering PS-NH2-coelomocytes interaction and toxicity. PS-NH2 did not
alter MXR phenotype but the observed dose-dependent decrease in calcein
accumulation suggests the ability of PS-NH2 to affect pump's efflux activity.
Overall results encourage additional studies on positively charged nanoplastics,
since the observed effects on sea urchin coelomocytes as well as the TPP corona
formation might represent a first step for addressing their impact on sensitive
marine species.
PMID- 29947276
TI - Age- and disease-dependent increase of the mitophagy marker phospho-ubiquitin in
normal aging and Lewy body disease.
AB - : Although exact causes of Parkinson disease (PD) remain enigmatic, mitochondrial
dysfunction is increasingly appreciated as a key determinant of dopaminergic
neuron susceptibility in both familial and sporadic PD. Two genes associated with
recessive, early-onset PD encode the ubiquitin (Ub) kinase PINK1 and the E3 Ub
ligase PRKN/PARK2/Parkin, which together orchestrate a protective mitochondrial
quality control (mitoQC) pathway. Upon stress, both enzymes cooperatively
identify and decorate damaged mitochondria with phosphorylated poly-Ub (p-S65-Ub)
chains. This specific label is subsequently recognized by autophagy receptors
that further facilitate mitochondrial degradation in lysosomes (mitophagy). Here,
we analyzed human post-mortem brain specimens and identified distinct pools of p
S65-Ub-positive structures that partially colocalized with markers of
mitochondria, autophagy, lysosomes and/or granulovacuolar degeneration bodies. We
further quantified levels and distribution of the 'mitophagy tag' in 2 large
cohorts of brain samples from normal aging and Lewy body disease (LBD) cases
using unbiased digital pathology. Somatic p-S65-Ub structures independently
increased with age and disease in distinct brain regions and enhanced levels in
LBD brain were age- and Braak tangle stage-dependent. Additionally, we observed
significant correlations of p-S65-Ub with LBs and neurofibrillary tangle levels
in disease. The degree of co-existing p-S65-Ub signals and pathological PD
hallmarks increased in the pre-mature stage, but decreased in the late stage of
LB or tangle aggregation. Altogether, our study provides further evidence for a
potential pathogenic overlap among different forms of PD and suggests that p-S65
Ub can serve as a biomarker for mitochondrial damage in aging and disease.
ABBREVIATIONS: BLBD: brainstem predominant Lewy body disease; CCCP: carbonyl
cyanide m-chlorophenyl hydrazone; DLB: dementia with Lewy bodies; DLBD: diffuse
neocortical Lewy body disease; EOPD: early-onset Parkinson disease; GVB:
granulovacuolar degeneration body; LB: Lewy body; LBD: Lewy body disease; mitoQC:
mitochondrial quality control; nbM: nucleus basalis of Meynert; PD: Parkinson
disease; PDD: Parkinson disease with dementia; p-S65-Ub: PINK1-phosphorylated
serine 65 ubiquitin; SN: substantia nigra; TLBD: transitional Lewy body disease;
Ub: ubiquitin.
PMID- 29947278
TI - A Voice Needs to be Heard: The Meaning of "Going Home".
AB - BACKGROUND: This case report addresses a client from a minority cultural
background in Australia and her complex cultural needs at the end of life. CASE
HISTORY: A 66-year-old Japanese female client diagnosed with renal cancer, and
lung and spine metastasis shared her story. Since a left nephrectomy in 2007, she
has had hemodialysis 3 days a week. She left Japan more than 30 years ago and
moved to Australia 20 years ago. With the 6-month prognosis, she expressed her
desire to "go home." The meaning of "going home" was explored with the author who
shares the same cultural background and language and is a palliative care nurse.
The meanings for wanting to go home were her nostalgia for the traditional food,
language, land, and death rituals. DISCUSSION: The client identified her
preferred place to die and discussed her death wishes. Open, honest communication
with health professionals about her condition and prognosis facilitated
meaningful discussions. CONCLUSION: The narrative demonstrates the complex issues
and needs of clients from minority cultural backgrounds and the importance of
understanding the real cultural meaning behind their stories. Exploring the
meaning with compassionate curiosity as well as interpretation support was the
key.
PMID- 29947279
TI - Diabetic Retinopathy -Incidence And Risk Factors In A Community Setting- A
Longitudinal Study.
AB - AIM: To evaluate the natural history of diabetic retinopathy (DR) in diabetic
patients and to assess long term risk for other chronic diseases associated with
DR. METHODS: Retrospective, community-based study. Diabetics who underwent their
first fundoscopic examination during 2000-2002, and had at least one follow- up
examination by the end of 2007 were included. The primary outcome was the
development of DR (proliferative diabetic retinopathy (PDR), non PDR (NPDR) or
macular edema. Patients were followed for another 9 years for documentation of
new diagnosis of related diseases. RESULTS: 516 patients' (1,032 eyes) records
were included and were followed first for an average of 4.15 +/- 1.27 years.
During follow-up, 28 (2.7%) of the total 1,032 eyes examined were diagnosed with
PDR. An additional 194 (18.8%) eyes were diagnosed with new NPDR. The cumulative
incidence of NPDR was 310/1,032 (30.0%). All the patients who developed PDR had
prior NDPR. By the end of the 9 years extended follow up, patients with NPDR had
a greater risk for developing chronic renal failure HR = 1.71 (1.14-2.56),
ischemic heart disease HR = 1.57 (1.17-2.09), and had an increased mortality rate
HR = 1.26 (1.02-1.57) Conclusion: DR is associated with a higher rate of diabetes
complications. Patients with DR should be followed more closely. Key points
During a mean follow-up of 4.5 years, the cumulative incidence of diabetic
retinopathy in a community cohort was 18.8%. NDPR (non-proliferative diabetic
retinopathy) is a predictor of PDR (proliferative diabetic retinopathy). In a
real life setting NPDR is a marker of a poorer prognosis. Patients with NDPR
should be monitored more closely.
PMID- 29947280
TI - In silico screening and identification of potential GSK3beta inhibitors.
AB - Glycogen synthase kinase-3beta (GSK3beta) has been reported for its impact on
multitude biological processes from cell proliferation to apoptosis. The increase
in the ratio of active/inactive GSK3beta is the major factor associated in the
etiology of several psychiatric diseases, diabetes, muscle hypertrophy,
neurodegenerative diseases, and some cancers. These findings made GSK3beta a
promising therapeutic target, and the interest in the discovery, synthesis of
novel drugs to effectively attenuate its function with probably no side effects
has been increasing in the chronology of GSK3beta drug discovery. In the present
study, we applied a combination of computational tools on a chemical library for
the virtual discovery of their potency to inhibit GSK3beta. The chemical library
was screened against a set of filters at different levels. Finally, five
compounds in the chemical library were found to potentially inhibit GSK3beta with
no toxic effects. Furthermore, binding mode analysis revealed that all the
compounds bound to the ATP site and most of the hydrogen bonding interactions are
conserved as in GSK3beta structures deposited in PDB.
PMID- 29947281
TI - Access to supportive care during and after cancer treatment and the impact of
socioeconomic factors.
AB - BACKGROUND: Sweden's national cancer strategy points out several areas of cancer
care that need improvements. Among them the need for supportive care resources to
be accessible through the entire cancer trajectory and the reduction of
socioeconomic inequalities. The aim of this study was to compare the patient
reported access to supportive care in the Stockholm-Gotland region between
patients diagnosed in 2014 and 2016. The aim was also to describe how
socioeconomic and other demographic factors impact access to supportive care.
MATERIAL AND METHODS: All patients with gynaecological, head and neck,
haematological and upper gastrointestinal cancers diagnosed in the Stockholm
Gotland regions were identified through the Swedish Cancer Registries. Data were
collected via a questionnaire on demographic, socioeconomic factors and patients'
perception (n = 1872) of access to supportive care. Data were summarized using
descriptive statistics and logistic regression was used for relevant variables.
RESULTS: Access to some supportive care resources, such as contact nurses (CNs)
and individual written care plans (IWCPs) had significantly improved from 2014 to
2016. The proportion of patients that had received information about patient
advocacy groups (PAGs) had also improved but remained on a relatively low level
(29 and 35%, respectively). The proportion of patients being refereed to
palliative care (PC) did not change between 2014 and 2016. In total, 10% of the
patients reported to having received information on second medical opinion (SMO).
Patients that had undergone multimodality cancer treatment were more likely to
report access to supportive care, and those with lower education levels were more
likely to have access to CNs and IWCPs. CONCLUSION: Access to some of the
supportive care resources have shown improvements in the Stockholm-Gotland region
but further efforts are required, especially regarding access to PC, information
about PAGs and SMOs.
PMID- 29947282
TI - Tomato 14-3-3 Proteins Are Required for Xv3 Disease Resistance and Interact with
a Subset of Xanthomonas euvesicatoria Effectors.
AB - The 14-3-3 phospho-binding proteins with scaffolding activity play central roles
in the regulation of enzymes and signaling complexes in eukaryotes. In plants, 14
3-3 isoforms are required for disease resistance and key targets of pathogen
effectors. Here, we examined the requirement of the tomato (Solanum lycopersicum)
14-3-3 isoform (TFT) protein family for Xv3 disease resistance in response to the
bacterial pathogen Xanthomonas euvesicatoria. In addition, we determined whether
TFT proteins interact with the repertoire of X. euvesicatoria type III secretion
effector proteins, including AvrXv3, the elicitor of Xv3 resistance. We show that
multiple TFT contribute to Xv3 resistance. We also show that one or more TFT
proteins physically interact with multiple effectors (AvrXv3, XopE1, XopE2, XopN,
XopO, XopQ, and XopAU). Genetic analyses indicate that none of the identified
effectors interfere with AvrXv3-elicited resistance into Xv3 tomato leaves;
however, XopE1, XopE2, and XopO are required to suppress symptom development in
susceptible tomato leaves. Phospho-peptide mapping revealed that XopE2 is
phosphorylated at multiple residues in planta and residues T66, T131, and S334
are required for maximal binding to TFT10. Together, our data support the
hypothesis that multiple TFT proteins are involved in immune signaling during X.
euvesicatoria infection.
PMID- 29947283
TI - Emerging Targets for the Treatment of Lupus Erythematosus: There is No Royal Road
to Treating Lupus.
AB - Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease
that preferentially affects women of child-bearing age. Most current treatments
for SLE with the exception of belimumab are not target-specific. Non-targeted
therapy such as corticosteroids, cyclophosphamide, and other immunosuppressive
drugs results in unwanted adverse effects. Although progress in treatment,
including supportive therapy, has dramatically improved the prognosis of patients
with SLE, better treatment drugs and protocols with fewer adverse effects and
higher efficacy for the most severe form of SLE are needed. Advancements in
genomics, immunology, and pathophysiology in the field of systemic autoimmunity
have provided physicians with increasing knowledge, but the most appropriate
treatment for each patient with SLE remains to be established. Therefore, the
search for novel treatment targets in patients with SLE is ongoing. This review
focuses on recent findings in the genetics of lupus and the abnormalities in
cellular interactions, cytokine profiles, and intracellular signaling in patients
with SLE. Novel molecular targets for lupus, mostly introduced through clinical
trials, are then discussed based on these findings.
PMID- 29947284
TI - Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long
Evans rats.
AB - Apelin has cardiopulmonary protective properties that promote vasodilation and
maintenance of the endothelial barrier. While reductions in apelin have been
identified as a contributor to various lung diseases, including pulmonary edema,
its role in the effect of air pollutants has not been examined. Thus, in the
current study, we sought to investigate if apelin is a downstream target of
inhaled ozone and if such change in expression is related to altered DNA
methylation in the lung. Male, Long-Evans rats were exposed to filtered air or
1.0 ppm ozone for 4 h. Ventilation changes were assessed using whole-body
plethysmography immediately following exposure, and markers of pulmonary edema
and inflammation were assessed in the bronchoaveolar lavage (BAL) fluid. The
enzymatic regulators of DNA methylation were measured in the lung, along with
methylation and hydroxymethylation of the apelin promoter. Data showed that ozone
exposure was associated with increased enhanced pause and protein leakage in the
BAL fluid. Ozone exposure reduced DNA cytosine-5-methyltransferase (DNMT)
activity and Dnmt3a/b gene expression. Exposure-induced upregulation of
proliferating cell nuclear antigen, indicative of DNA damage, repair, and
maintenance methylation. Increased methylation and reduced hydroxymethylation
were measured on the apelin promoter. These epigenetic modifications accompanied
ozone-induced reduction of apelin expression and development of pulmonary edema.
In conclusion, epigenetic regulation, specifically increased methylation of the
apelin promoter downstream of DNA damage, may lead to reductions in protective
signaling of the apelinergic system, contributing to the pulmonary edema observed
following the exposure to oxidant air pollution.
PMID- 29947285
TI - The Use of Aromatherapy to Reduce Chemotherapy-Induced Nausea in Children With
Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial.
AB - INTRODUCTION: Chemotherapy-induced nausea can be distressing and difficult to
manage in children with cancer. The purpose of this study was to investigate the
utility of ginger aromatherapy in relieving chemotherapy-induced nausea in
children with cancer. METHOD: This randomized, double-blind, placebo-controlled
study of 49 children with cancer explored whether inhalation of the aroma of
essential oil of ginger during chemotherapy decreased nausea compared with a
placebo (water) or control (Johnson's baby shampoo) measured by prechemotherapy
and postchemotherapy assessment with the Pediatric Nausea Assessment Tool
(PeNAT). RESULTS: While well received, well tolerated, nontoxic, and noninvasive,
ginger aromatherapy did not significantly decrease nausea in patients enrolled in
this study. Among 21 patients who indicated feeling nausea prechemotherapy, 67%
reported improvement, 5% worsening, and 28% no change in their postinfusion PeNAT
score. We failed to detect a statistical significant difference in the change in
PeNAT scores among the three groups.
PMID- 29947286
TI - Mapping of ribosomal 23S ribosomal RNA modifications in Clostridium sporogenes.
AB - All organisms contain RNA modifications in their ribosomal RNA (rRNA), but the
importance, positions and exact function of these are still not fully elucidated.
Various functions such as stabilizing structures, controlling ribosome assembly
and facilitating interactions have been suggested and in some cases
substantiated. Bacterial rRNA contains much fewer modifications than eukaryotic
rRNA. The rRNA modification patterns in bacteria differ from each other, but too
few organisms have been mapped to draw general conclusions. This study maps 23S
ribosomal RNA modifications in Clostridium sporogenes that can be characterized
as a non-toxin producing Clostridium botulinum. Clostridia are able to sporulate
and thereby survive harsh conditions, and are in general considered to be
resilient to antibiotics. Selected regions of the 23S rRNA were investigated by
mass spectrometry and by primer extension analysis to pinpoint modified sites and
the nature of the modifications. Apparently, C. sporogenes 23S rRNA contains few
modifications compared to other investigated bacteria. No modifications were
identified in domain II and III of 23S rRNA. Three modifications were identified
in domain IV, all of which have also been found in other organisms. Two unusual
modifications were identified in domain V, methylated dihydrouridine at position
U2449 and dihydrouridine at position U2500 (Escherichia coli numbering), in
addition to four previously known modified positions. The enzymes responsible for
the modifications were searched for in the C. sporogenes genome using BLAST with
characterized enzymes as query. The search identified genes potentially coding
for RNA modifying enzymes responsible for most of the found modifications.
PMID- 29947287
TI - The plastid-nucleus located DNA/RNA binding protein WHIRLY1 regulates microRNA
levels during stress in barley (Hordeum vulgare L.).
AB - In this article a novel mechanism of retrograde signaling by chloroplasts during
stress is described. This mechanism involves the DNA/RNA binding protein WHIRLY1
as a regulator of microRNA levels. By virtue of its dual localization in
chloroplasts and the nucleus of the same cell, WHIRLY1 was proposed as an
excellent candidate coordinator of chloroplast function and nuclear gene
expression. Comparison of wild-type and transgenic plants with an RNAi-mediated
knockdown of WHIRLY1 showed, that the transgenic plants were unable to cope with
continuous high light conditions. They were impaired in production of several
microRNAs mediating post-transcriptional responses during stress. The results
support a central role of WHIRLY1 in retrograde signaling and also underpin a so
far underestimated role of microRNAs in this process.
PMID- 29947288
TI - Growth of Cutibacterium acnes is common on osteosynthesis material of the
shoulder in patients without signs of infection.
AB - Background and purpose - Cutibacterium acnes, formerly known as Propionibacterium
acnes, is often isolated from deep tissues of the shoulder. It is recognized as
an important causative agent of foreign-material associated infections. However,
the incidence and significance of its detection in tissues from patients without
clinical evidence for infection is unclear. We assessed the incidence of C. acnes
colonization of osteosynthesis material in asymptomatic patients, and evaluated
the short-term outcome in relation to the microbiological findings. Patients and
methods - We microbiologically analyzed osteosynthesis material of 34
asymptomatic patients after surgery on the clavicle. Material obtained from 19
asymptomatic patients after osteosynthesis of the fibula served as a control
group. Patients were clinically followed up for 3-24 months after removal of the
osteosynthesis material. Results - Bacteria were recovered from devices in 29 of
34 patients from the clavicle group. 27 of 29 positive samples grew C. acnes.
Isolation of C. acnes was more common in male than in female patients. No
bacterial growth was observed on foreign material from patients in the fibula
group. All patients remained asymptomatic at follow-up. Interpretation - Growth
of C. acnes is common on osteosynthesis material of the shoulder, especially in
males. Samples were positive irrespective of clinical signs of infection.
Therefore, detection of C. acnes in this clinical setting is of questionable
clinical significance. The high positivity rate in asymptomatic patients
discourages routine sampling of material in cases without clinical evidence for
infection.
PMID- 29947289
TI - Systemic Estrone Production and Injury-Induced Sex Hormone Steroidogenesis after
Severe Traumatic Brain Injury: A Prognostic Indicator of Traumatic Brain Injury
Related Mortality.
AB - Extensive pre-clinical studies suggest that sex steroids are neuroprotective in
experimental traumatic brain injury (TBI). However, clinical trials involving sex
hormone administration have not shown beneficial results, and our observational
cohort studies show systemic estradiol (E2) production to be associated with
adverse outcomes. Systemic E2 is produced via aromatization of testosterone (T)
or reduction of estrone (E1). E1, also produced via aromatization of
androstenedione (Andro) and is a marker of T-independent E2 production. We
hypothesized that E1 would be (1) associated with TBI-related mortality, (2) the
primary intermediate for E2 production, and (3) associated with adipose tissue
specific aromatase transcription. We assessed 100 subjects with severe TBI and 8
healthy controls. Serum levels were measured on days 0-3 post-TBI for key
steroidogenic precursors (progesterone), aromatase pathway intermediates (E1, E2,
T, Andro), and the adipose tissue-specific aromatase transcription factors
cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). E1
was elevated after TBI versus controls. High E1 was associated with higher
progesterone, cortisol, and IL-6 (p < 0.05). Multivariable logistic regression
demonstrated that those in the highest E1 tertile had increased odds for
mortality (adjusted OR = 5.656, 95% CI = 1.102-29.045, p = 0.038). Structural
equation models show that early serum E2 production is largely T independent,
occurring predominantly through E1 metabolism. Acute serum E1 functions as a
mortality marker for TBI through aromatase-dependent E1 production and T
independent E2 production. Further work should evaluate risk factors for high E2
production and how systemic E2 and its key intermediate E1 contribute to the
extracerebral consequences of severe TBI.
PMID- 29947290
TI - The Application of Medical Thermography to Discriminate Neuroischemic Toe
Ulceration in the Diabetic Foot.
AB - This study aimed to determine whether thermal imaging can detect temperature
differences between healthy feet, nonulcerated neuroischemic feet, and
neuroischemic feet with toe ulcers in patients with type 2 diabetes mellitus
(T2DM). Participants were prospectively divided into 3 groups: T2DM without foot
problems; a healthy, nonulcerated neuroischemic group, and an ulcerated
neuroischemic group. Thermal images of the feet were obtained with automated
segmentation of regions of interest. Thermographic images from 43 neuroischemic
feet, 21 healthy feet, and 12 neuroischemic feet with active ulcer in one of the
toes were analyzed. There was a significant difference in toe temperatures
between the 3 groups ( P = .001), that is, nonulcerated neuroischemic (n = 181;
mean temperature = 27.7 degrees C [+/-2.16 SD]) versus neuroischemic ulcerated (n
= 12; mean temperature = 28.7 degrees C [+/-3.23 SD]), and healthy T2DM group (n
= 104; mean temperature = 24.9 degrees C [+/-5.04 SD]). A post hoc analysis
showed a significant difference in toe temperatures between neuroischemic
nonulcerated and healthy T2DM groups ( P = .001), neuroischemic ulcerated and
healthy groups ( P = .001). However, no significant differences in toe
temperatures were identified between the ulcerated neuroischemic and nonulcerated
neuroischemic groups ( P = .626). There were no significant differences between
the ulcerated toes (n = 12) and the nonulcerated toes (n = 57) of the same foot
in the ulcerated neuroischemic group ( P = .331). Toe temperatures were
significantly higher in neuroischemic feet with or without ulceration compared
with healthy feet in patients with T2DM. There were no significant differences in
temperatures of ulcerated toes and the nonulcerated toes of the same foot,
implying that all the toes of the same foot could potentially be at risk of
developing complications, which can be potentially detected by infrared
thermography.
PMID- 29947292
TI - "Why did I get that part of you?" Understanding addiction genetics through family
history.
AB - Scientists have sought to uncover the genetic bases of many diseases and
disorders. In response, scholars defined "geneticization" to describe genetic
infiltration of understandings of health and illness. In our research, we
interviewed 63 individuals in addiction treatment programs to identify what form
of geneticization best fits individuals' description of their own addiction.
Individuals' narratives of their lives, which include family history and are
influenced by cultural and structural factors, affect respondents' reactions to a
potential genetic basis of addiction. Most who had a family history of addiction
subscribed to a notion that addiction "runs in families," while most who lacked a
family history of addiction used this fact to reject the notion of genetic
inheritance of addiction. We conclude that though we see elements of several
different versions of geneticization, Nikolas Rose's version, that genetics
affects peoples' perceptions of addiction in small but important ways, best
describes our respondents' views.
PMID- 29947291
TI - Serum Metabolites Associated with Computed Tomography Findings after Traumatic
Brain Injury.
AB - There is a need to rapidly detect patients with traumatic brain injury (TBI) who
require head computed tomography (CT). Given the energy crisis in the brain
following TBI, we hypothesized that serum metabolomics would be a useful tool for
developing a set of biomarkers to determine the need for CT and to distinguish
among different types of injuries observed. Logistical regression models using
metabolite data from the discovery cohort (n = 144, Turku, Finland) were used to
distinguish between patients with traumatic intracranial findings and those with
negative findings on head CT. The resultant models were then tested in the
validation cohort (n = 66, Cambridge, United Kingdom). The levels of glial
fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also
quantified in the serum from the same patients. Despite there being significant
differences in the protein biomarkers in patients with TBI, the model that
determined the need for a CT scan validated poorly (area under the curve [AUC] =
0.64: Cambridge patients). However, using a combination of six metabolites (two
amino acids, three sugar derivatives, and one ketoacid) it was possible to
discriminate patients with intracranial abnormalities on CT and patients with a
normal CT (AUC = 0.77 in Turku patients and AUC = 0.73 in Cambridge patients).
Further, a combination of three metabolites could distinguish between diffuse
brain injuries and mass lesions (AUC = 0.87 in Turku patients and AUC = 0.68 in
Cambridge patients). This study identifies a set of validated serum polar
metabolites, which associate with the need for a CT scan. Additionally, serum
metabolites can also predict the nature of the brain injury. These metabolite
markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics
and radiation load.
PMID- 29947293
TI - Correlation between neurobehavioural assessment and functional magnetic resonance
imaging in the diagnosis of prolonged disorders of consciousness.
AB - The misdiagnosis rate of prolonged disorders of consciousness remains at
approximately 40%, owing to overlap between diagnostic criteria and
inconsistencies in patient responses. Improved accuracy is essential for the
appropriate provision of treatment and rehabilitation. Neuroimaging may provide
additional diagnostic information to standard neurobehavioural assessment,
enabling identification of higher levels of awareness. In this study, the Sensory
Tool to Assess Responsiveness (STAR) neurobehavioural assessment was used to
assess the level of awareness of 19 patients with prolonged disorders of
consciousness. Patients also completed an fMRI diagnostic assessment. The degree
of concordance between fMRI and STAR diagnoses was substantial, despite
significant delays for some patients between the two assessments. Discrepant
diagnoses may relate to this delay or to the inconsistency of responses which
characterise the minimally conscious state. The findings indicate that fMRI
neuroimaging and STAR neurobehavioural assessment, while largely concordant, may
identify different facets of awareness in some patients, which supports the use
of both types of assessment in forming a diagnosis. Recommendations for future
research include minimal delays between neurobehavioural and neuroimaging
assessment, larger patient cohorts, and the use of multiple shorter fMRI
assessments which provide more opportunities for patients to exhibit relevant
behaviours.
PMID- 29947294
TI - Examining the role of self-regulation and emotion in clinical reasoning:
Implications for developing expertise.
AB - This paper explores the role that self-regulation and emotions play in
establishing a clinical diagnosis in the context of solving a clinical case in
BioWorld, a computer supported learning environment designed for medical students
to practice clinical reasoning. Group differences between high and low performers
were explored. The results revealed no group differences in overall measures of
SRL but high performers spend more time than lows in a subcategory of the
reflection phase (reflecting on prioritized evidence and results). A reciprocal
role of emotions was demonstrated for clinical reasoning and predicted students'
diagnostic performance. High performers showed less negative activating emotions
than low performers.
PMID- 29947295
TI - Analysis of reversed L-loops as closing loops with anterior intrusive force.
AB - OBJECTIVE: Intrusive forces on anterior brackets are preferable for avoiding
overbite deepening. Reversing plain L-loops may create such advantageous force
system during space closure. DESIGN: Force systems of reversed L-loops were
compared with T-loops at three interbracket distances (IBD). SETTING:
Computational study. METHODS: Using finite element analysis, loop response during
simulated loop-pulling was determined for plain reversed L- and T-loop
configurations at three IBDs and two sizes. Force systems were calculated on both
loop ends for two activation forces. RESULTS: The 12 mm IBD reversed L-loops had
almost equal M/F ratios in opposite directions at both ends. A small intrusive
force was found at the canine bracket (CB). The 6 mm IBD reversed L-loops showed
larger M/F ratios and extrusive forces at the premolar bracket (PB) and smaller
M/F with intrusive forces at CB. The force system of 12 mm IBD T-loops showed the
similar force systems as off-centered V-bends with extrusive force at CB, whilst
plain 6 mm IBD T-loops showed properties similar to centered V-bends with less
extrusive force at CB. CONCLUSIONS: Reversed L closing loops placed no extrusive
force on the CB end at various IBDs, indicating that reversed loops will generate
an intrusive force at anterior teeth during space closure.
PMID- 29947296
TI - Directional Bias for Vertical Integration of Motion Trajectories.
AB - Here we report a new ambiguous continuous motion display, in which two objects
appear at the diagonally opposite corners of an imaginary square, move along the
diagonal axis toward each other, and after meeting in the center, shift their
trajectories to the other two diagonal corners. This display can be seen as two
objects' colliding and bouncing off each other, with two competing
interpretations of trajectory configuration requiring either vertical or
horizontal integration of trajectory segments. Despite the fact that both
percepts are equally plausible, the current study revealed a perceptual
preference toward a vertical integration interpretation. We compared this bias
with the similar vertical bias in a bistable apparent motion quartet, which
suggests that the directional anisotropy found here is quite a new, and distinct
phenomenon in both its perceptual characteristics and underlying mechanism.
PMID- 29947297
TI - Universal Phonological Features.
AB - The Theory of universal grammar suggests that human languages may share some
similarities at the phonological level. Based on this hypothesis, we further
propose a language generalization effect (LGE) and hypothesize that people may
inherit the universal phonological features from their native languages and then
transfer them to foreign languages. To test this hypothesis, in two experiments,
participants listened to a pair of normal and syllable reversed recordings
(Experiments 1a-1d) or normal and phonemic reversed recordings (Experiments 2a
2d) in unknown and native languages and reported their similarities. The results
indicated that participants were more sensitive to the dissimilarities of normal
recordings than to reversed ones. These results suggest that participants could
identify the universal phonological features from normal recordings, but not
reversed ones, and then adopt these features to better verify the dissimilarities
of normal recordings. In sum, the current study first proposed the LGE and
reported primary evidence to support it.
PMID- 29947298
TI - Typicality or Fluency?
AB - The modern Japanese writing system comprises different scripts, such as Kanji,
Hiragana, and Katakana. These scripts differ greatly in both typicality and
frequency of usage. In two experimental studies using names of cities or
prefectures in Japan as target stimuli, we examined two hypotheses, the
typicality hypothesis and fluency hypothesis, in order to assess effects of
Japanese script on psychological processes. It was found that Kanji names induced
typical thinking in a participant's description of a location, whereas Katakana
names induced rather nontypical thinking. In contrast, we found that script
differences did not affect distance estimations. We discuss these effects of
Japanese script on psychological processes in terms of the typicality hypothesis
(differences in typical usage habits between Kanji and Katakana that affect
psychological processes).
PMID- 29947299
TI - Pediatric intussusception and early discharge after pneumatic reduction.
AB - OBJECTIVE: The success of non-operative reduction methods is extremely high in
pediatric intussusceptions. Recurrent intussusceptions are also well-known
entities in the pediatric age group after non-operative and operative reduction.
Historical recommendations include a 24- to 48-h observation period after
reduction. This situation often leads to unnecessary time loss. We aimed to show
that early discharge does not pose a significant risk. METHODS: The medical
records of patients who presented to our hospital between January 2008 and June
2017 were retrospectively reviewed. Data collected included age, clinical
presentation, procedural information, surgical intervention, hospital stay, and
presence of recurrence. RESULTS: A total of 62 patients were included the study.
Non-operative reduction was successful in 58 of 62 patients (93.5%). Four
patients with failed non-operative reduction underwent subsequent surgical
procedures. All patients were allowed oral intake within 2-4 h (mean: 2.6 h)
after successful non-operative reduction and discharged within 5-8 h (mean: 6.2
h) after reduction. There were five episodes of recurrence and none occurred in
the first 48 h after reduction. All recurrences were treated with non-operative
reduction as in the first attempt. There were no problems detected in short- or
long-term follow-ups. CONCLUSION: Pneumatic reduction is a safe and effective
method in pediatric intussusception. If one is confident about treatment success,
patients can be discharged without a long observation period. Early discharge is
also cost-effective and reduces time loss.
PMID- 29947300
TI - Motivational profiles in table tennis players: Relations with performance anxiety
and subjective vitality.
AB - Research has suggested the need to use a person-centred approach to examine
multidimensionality of motivation. Guided by self-determination theory (Deci &
Ryan, 1985), the primary aim of the present study was to examine the motivational
profiles in table tennis players and their composition by gender, country,
training status, and competition levels (from recreational to international). The
secondary aim was to examine the differences in performance anxiety and
subjective vitality across the motivational profiles. Participants were 281 table
tennis players from multiple countries, mostly the U.S. and China. Hierarchical
and nonhierarchical cluster analyses were conducted and showed three motivational
profiles with distinct quantity and quality: "low", "controlled", and "self
determined". Chi-square tests of independence demonstrated significant
differences in their cluster membership by country, formal training with a coach,
and competition levels, but not gender. MANCOVA results indicated differences in
performance anxiety and subjective vitality across the motivational profiles, in
which the controlled profile had the greatest anxiety symptoms. These differences
are attributed to the quality over quantity of motivation, which have meaningful
implications for table tennis coaches and sport psychology consultants to
diagnose and intervene with players in order to reduce their performance anxiety
and improve their well-being.
PMID- 29947301
TI - Living a successful weight loss after severe obesity.
AB - PURPOSE: Losing weight and keeping it off for the long term is difficult. Weight
regain is common. Experiences of successful non-surgical weight loss after severe
obesity are largely unexplored. We know little about long-term weight loss
processes, and how health care services can be of help to those living them.
METHODS: Drawing on in-depth interviews of 8 women and 2 men, the aim of this
phenomenological study is to describe the experiences of adults who have been
severely obese, who have lost weight and maintained weight loss for the long term
(>5 years). RESULTS: Findings show that after severe obesity, sustained weight
loss has no endpoint, yet is always easy to end. Keeping weight off means
committing to oneself, continuing profound changes and cultivating sensitivity
towards oneself and others. A phenomenological understanding of sustained weight
loss can inform professionals who deal with health issues and challenges
occurring in the life of people leaving severe obesity.
PMID- 29947303
TI - Feasibility of Induced Pluripotent Stem Cell Therapies for Treatment of Type 1
Diabetes.
AB - IMPACT STATEMENT: This review of iPSCs to treat T1D provides a current assessment
of the challenges and potential for this proposed new therapy.
PMID- 29947302
TI - The association of single nucleotide polymorphisms of Toll-like receptor 3, Toll
like receptor 7 and Toll-like receptor 8 genes with the susceptibility to HCV
infection.
AB - BACKGROUND: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs)
are linked with functional modification of cytokine responses. In chronic
hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily
targeted receptor pathways implicated in viral immune responses. We hypothesized
that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different
outcomes of HCV infection. MATERIALS & METHODS: A total of 3368 subjects from 850
families were recruited and divided into three main groups categorized as chronic
HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were
genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using
allelic discrimination real-time PCR. RESULTS: Carriage of the C allele in three
SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7
(rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only
were significantly higher in SVC group than CHC group (P < 0.001), while carriage
of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8
(rs3764880) in both males and females were significantly higher in CHC infection
more than SVC group (P < 0.001). CONCLUSION: The C allele is protective of HCV in
TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while
risk of infection is linked to the T allele in TLR7 (rs179008) in females only
and the A allele in TLR8 (rs3764880) in both sexes.
PMID- 29947307
TI - A data-driven method for identifying shorter symptom criteria sets: the case for
DSM-5 alcohol use disorder.
AB - BACKGROUND: Although the DSM is a widely used diagnostic guide, lengthy criteria
sets can be problematic and provide the primary motivation to identify short
forms. Using the 11 diagnostic criteria provided by the DSM-5 for alcohol use
disorder (AUD), the present study develops a data-driven method to systematically
identify subsets and associated cut-offs that yield diagnoses as similar as
possible to use all 11 criteria. METHOD: Relying on data from the National
Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III), our
methodology identifies diagnostic short-forms for AUD by: (1) maximizing the
association between the sum scores of all 11 criteria with newly constructed
subscales from subsets of criteria; (2) optimizing the similarity of AUD
prevalence between the current DSM-5 rule and newly constructed diagnostic short
forms; (3) maximizing sensitivity and specificity of the short-forms against the
current DSM-5 rule; and (4) minimizing differences in the accuracy of the short
form across chosen covariates. Replication is shown using NESARC-Wave 2. RESULTS:
More than 11 000 diagnostic short-forms for DSM-5 AUD can be created and our
method narrows down the optimal choices to eight. Results found that 'Neglecting
major roles' and 'Activities given up' could be dropped with practically no
change in who is diagnosed (specificity = 100%, sensitivity ? 99.6%) or the
severity of those diagnosed (kappa = 0.97). CONCLUSIONS: With a continuous
improvement model adopted by the APA for DSM revisions, we offer a data-driven
tool (a SAS Macro) that identifies diagnostic short-forms in a systematic and
reproducible way to help advance potential improvements in future DSM revisions.
PMID- 29947308
TI - Childhood dietary trajectories and adolescent cardiovascular phenotypes:
Australian community-based longitudinal study.
AB - OBJECTIVE: With the intention to inform future public health initiatives, we
aimed to determine the extent to which typical childhood dietary trajectories
predict adolescent cardiovascular phenotypes. DESIGN: Longitudinal study.
Exposure was determined by a 4 d food diary repeated over eight waves (ages 4-15
years), coded by Australian Dietary Guidelines and summed into a continuous diet
score (0-14). Outcomes were adolescent (Wave 8, age 15 years) blood pressure,
resting heart rate, pulse wave velocity, carotid intima-media thickness, retinal
arteriole-to-venule ratio. Latent class analysis identified 'typical' dietary
trajectories from childhood to adolescence. Adjusted linear regression models
assessed relationships between trajectories and cardiovascular outcomes, adjusted
for a priori potential confounders. SETTING: Community sample, Melbourne,
Australia. SUBJECTS: Children (n 188) followed from age 4 to 15 years. RESULTS:
Four dietary trajectories were identified: unhealthy (8 %); moderately unhealthy
(25 %); moderately healthy (46 %); healthy (21 %). There was little evidence that
vascular phenotypes associated with the trajectories. However, resting heart rate
(beats/min) increased (beta; 95 % CI) across the healthy (reference), moderately
healthy (4.1; -0.6, 8.9; P=0.08), moderately unhealthy (4.5; -0.7, 9.7; P=0.09)
and unhealthy (10.5; 2.9, 18.0; P=0.01) trajectories. CONCLUSIONS: Decade-long
dietary trajectories did not appear to influence macro- or microvascular
structure or stiffness by mid-adolescence, but were associated with resting heart
rate, suggesting an early-life window for prevention. Larger studies are needed
to confirm these findings, the threshold of diet quality associated with these
physiological changes and whether functional changes in heart rate are followed
by phenotypic change.
PMID- 29947309
TI - "Impossible" patients in oncology: Two unusual cases.
AB - OBJECTIVE: Cancer patients can present with impossible behavior, which can
jeopardize their treatment and challenge healthcare professionals' teamwork.
METHOD: Report of two unusual psychiatric cases, including Munchausen and Peter
Pan syndromes, which occurred in a comprehensive cancer center.ResultGuidelines
in medical and surgical wards are suggested to address such situations regarding
oncologic compliance.Significance of resultsMultidisciplinary collaboration
between medical and surgical teams and the psycho-oncologic department is highly
recommended.
PMID- 29947310
TI - Access to awareness of direct gaze is related to autistic traits.
AB - BACKGROUND: The atypical processing of eye contact is a characteristic hallmark
of autism spectrum disorder (ASD). The severity of these symptoms, however, is
thought to lie on a continuum that extends into the typical population. While
behavioural evidence shows that differences in social cognitive tasks in
typically developed (TD) adults are related to the levels of autistic-like
traits, it remains unknown whether such a relation exists for the sensitivity to
direct gaze. METHODS: In two experiments, we measured reaction times to detect
the faces with direct and averted gaze, suppressed from awareness, i.e. the
access to awareness. In experiment 1, we tested N = 19 clinically diagnosed
adults with ASD and N = 22 TD matched controls, while in experiment 2, we tested
an independent sample of N = 20 TD adults. RESULTS: In line with the literature,
experiment 1 showed preferential processing of direct gaze in the TD group but
not in the ASD group. Importantly, we found a linear relationship in both
experiments between the levels of autistic traits within the groups of TD
participants and their sensitivity to direct gaze: with increasing autistic
characteristics, there was a decrease in sensitivity to direct gaze. CONCLUSION:
These results provide the first evidence that differences in gaze processing and
the sensitivity to direct gaze are already present in individuals with
subclinical levels of autistic traits. Furthermore, they lend support to the
continuum view of the disorder and could potentially help in an earlier diagnosis
of individuals at high risk for autism.
PMID- 29947315
TI - Assessment of decision-making capacity in patients requesting assisted suicide.
AB - SummaryIn this editorial, we argue that current attitudes toward terminally ill
patients are generally too paternalistic, and that it is wrong to assume that
patients suffering from mental health issues (including depression) cannot
consent to assisted suicide.Declaration of interestNone.
PMID- 29947313
TI - Significant concordance of genetic variation that increases both the risk for
obsessive-compulsive disorder and the volumes of the nucleus accumbens and
putamen.
AB - BACKGROUND: Many studies have identified changes in the brain associated with
obsessive-compulsive disorder (OCD), but few have examined the relationship
between genetic determinants of OCD and brain variation.AimsWe present the first
genome-wide investigation of overlapping genetic risk for OCD and genetic
influences on subcortical brain structures. METHOD: Using single nucleotide
polymorphism effect concordance analysis, we measured genetic overlap between the
first genome-wide association study (GWAS) of OCD (1465 participants with OCD,
5557 controls) and recent GWASs of eight subcortical brain volumes (13 171
participants). RESULTS: We found evidence of significant positive concordance
between OCD risk variants and variants associated with greater nucleus accumbens
and putamen volumes. When conditioning OCD risk variants on brain volume,
variants influencing putamen, amygdala and thalamus volumes were associated with
risk for OCD. CONCLUSIONS: These results are consistent with current OCD
neurocircuitry models. Further evidence will clarify the relationship between
putamen volume and OCD risk, and the roles of the detected variants in this
disorder.Declaration of interestThe authors have declared that no competing
interests exist.
PMID- 29947316
TI - Are we ready to use nature gardens to treat stress-related illnesses?
AB - SummaryIn this issue, Stigsdotter et al show that nature gardens offer similar
benefits to cognitive-behavioural therapy for managing stress-related illnesses
among people on sick leave. There is scope for pragmatic trials to establish the
processes involved and highlight the co-benefits that nature gardens offer for
health and the environment.Declaration of interestNone.
PMID- 29947317
TI - Green psychiatry: natural environments, developmental trauma and anxiety.
PMID- 29947319
TI - Greater Dietary Inflammatory Index score is associated with higher likelihood of
chronic kidney disease.
AB - Chronic kidney disease (CKD) is described as a progressive alteration of kidney
function, resulting from multiple factors, including behaviours. We investigated
the association of the Dietary Inflammatory Index (DII(r)) with prevalent CKD in
adult Americans. National Health and Nutrition Examination Survey participants
with measured data on kidney function markers from 2005 to 2012 were included in
this study. Prevalent CKD was based on an estimated glomerular filtration rate
(eGFR) <60 ml/min per 1.73 m2 or urinary albumin/creatinine>=30 mg/g. Energy
adjusted DII (E-DIITM) scores were calculated from 24-h dietary recalls.
Statistical analyses accounted for the survey design and sample weights. We
included 21 649 participants, with 1634 (6.8 %) having prevalent CKD.
Participants with high E-DII scores had greater BMI, fasting blood glucose and
systolic blood pressure, and were more likely to be diabetic or hypertensive (all
P<0.001) compared with those with lower E-DII scores. In regression models
adjusted for age, sex, race, fasting blood glucose, blood pressure, BMI,
hypertension and diabetes status, mean eGFR significantly decreased across
increasing quartiles of E-DII, whereas serum uric acid level and log urinary
albumin:creatinine ratio significantly increased (all P<0.001). Prevalent CKD
increased from 5.3 % in the lowest to 9.3 % in the highest E-DII quartile
(P=0.02). In multivariable-adjusted logistic regression models, the odds of
prevalent CKD were 29 % higher in the highest compared with the lowest E-DII
quartile. Pro-inflammatory diet is associated with declining kidney function and
high prevalence of CKD. Dietary changes that reduce inflammation have a potential
to prevent CKD.
PMID- 29947320
TI - Nutritional status and human milk intake of exclusively breast-fed infants at
high altitude in La Paz, Bolivia.
AB - Breast-feeding habits are related to the nutritional status and the risk of
illness and death in children under 2 years of age. For the first 6 months,
infants should be exclusively breast-fed. This study aimed to evaluate the
relationship between the infant's nutritional status and human milk intake by
breast-fed infants at high altitude. A quantitative, descriptive, correlational
study was conducted including mother/baby pairs of infants aged 2-6 months. The
amount of human milk consumed by the infants was assessed by the deuterium oxide
dose-to-mother technique. The lipid content of human milk was measured by
creamatocrit, and anthropometric measurements were performed. A total of eighteen
mother/baby pairs were assessed. The mean human milk intake was 888 (sd 149) g/d,
and the intake of water from other sources was 24.3 (sd 29.8) g/d. The lipid
content in human milk was 41 (sd 12) g/l. The infant's nutritional indicators
were normal in all cases. A moderate positive correlation was found between milk
volume and z scores weight-for-length r 0.58 (P=0.01), BMI-for-age r 0.56
(P=0.01) and weight-for-age r 0.45 (P=0.05). There was no correlation with length
for-age z score. The mean of breast milk intake in this study was similar to that
found in other studies in the world. The lipid content is comparable to similar
studies and was within the normal range. Children older than 3 months showed
signs of stunting despite adequate volume and lipid content of breast milk.
PMID- 29947318
TI - Gratitude, resignation and the desire for dignity: lived experience of food
charity recipients and their recommendations for improvement, Perth, Western
Australia.
AB - OBJECTIVE: The present study explored recipients' perceptions of food charity and
their suggested improvements in inner-city Perth, Western Australia. DESIGN: In
depth interviews were conducted with charitable food service (CFS) recipients.
Transcripts were thematically analysed using a phenomenological approach.
SETTING: Interviews were conducted at two CFS in inner-city Perth. SUBJECTS:
Fourteen adults. RESULTS: The recipients' journeys to a reliance on CFS were
varied and multifactorial, with poverty, medical issues and homelessness common.
The length of time recipients had relied on food charity ranged from 8 months to
over 40 years. Most were 'grateful yet resigned', appreciative of any food and
resigned to the poor quality, monotony and their unmet individual preferences.
They wanted healthier food, more variety and better quality. Accessing services
was described as a 'full-time job' fraught with unreliable information and
transport difficulties. They called for improved information and assistance with
transport. 'Eroded dignity' resulted from being fed without any choice and
queuing for food in public places, often in a volatile environment. 'Food
memories and inclusion' reflected a desire for commensality. Recipients suggested
services offer choice and promote independence, focusing on their needs both
physical and social. CONCLUSIONS: Although grateful, long-term CFS recipients
described what constitutes a voluntary failure. Their service improvement
recommendations can help meet their nutritional and social needs. A successful
CFS provides a food service that prioritises nutritious, good-quality food and
individual need, while promoting dignity and social inclusion, challenging in the
current Australian context.
PMID- 29947321
TI - Phytic acid improves intestinal mucosal barrier damage and reduces serum levels
of proinflammatory cytokines in a 1,2-dimethylhydrazine-induced rat colorectal
cancer model.
AB - Phytic acid (PA) has been demonstrated to have a potent anticarcinogenic activity
against colorectal cancer (CRC). Defects of the intestinal mucosal barrier and
inflammation processes are involved in the development and progression of CRC. In
the present study, we evaluated the effect of PA on the intestinal mucosal
barrier and proinflammatory cytokines. After a 1-week acclimatisation period,
sixty Wistar male rats were divided into the following five groups, with twelve
rats per group: the control group (CG), model group (MG), low-PA-dose group (0.25
g/kg per d), middle-PA-dose group (0.5 g/kg per d), and high-PA-dose group (1
g/kg per d). 1,2-Dimethylhydrazine (DMH) at a dosage of 30 mg/kg of body weight
was injected weekly to induce CRC for 18 weeks. We examined the expression of
genes related to the intestinal mucosal barrier in the model. The results
demonstrated that tumour incidence was decreased following PA treatment. The mRNA
and protein expression of mucin 2 (MUC2), trefoil factor 3 (TFF3) and E-cadherin
in the MG were significantly lower than those in the CG (P<0.05). The mRNA and
protein expression of claudin-1 in the MG were significantly higher than those in
the CG (P<0.05). PA elevated the mRNA and protein expression of MUC2, TFF3 and E
cadherin, and diminished the mRNA and protein expression of claudin-1.
Furthermore, PA decreased serum levels of proinflammatory cytokines, which
included TNF-alpha, IL-1beta and IL-6. In conclusion, this study suggests that PA
has favourable effects on the intestinal mucosal barrier and may reduce serum
proinflammatory cytokine levels.
PMID- 29947322
TI - Improvements in clinical characteristics of patients with non-alcoholic fatty
liver disease, after an intervention based on the Mediterranean lifestyle: a
randomised controlled clinical trial.
AB - Lifestyle interventions remain the cornerstone therapy for non-alcoholic fatty
liver disease (NAFLD). This randomised controlled single-blind clinical trial
investigated the effect of Mediterranean diet (MD) or Mediterranean lifestyle,
along with weight loss, in NAFLD patients. In all, sixty-three overweight/obese
patients (50 (sd 11) years, BMI=31.8 (sd 4.5) kg/m2, 68 % men) with
ultrasonography-proven NAFLD (and elevated alanine aminotransferase (ALT) and/or
gamma-glutamyl transpeptidase (GGT) levels) were randomised to the following
groups: (A) control group (CG), (B) Mediterranean diet group (MDG) or (C)
Mediterranean lifestyle group (MLG). Participants of MDG and MLG attended seven
60-min group sessions for 6 months, aiming at weight loss and increasing
adherence to MD. In the MLG, additional guidance for increasing physical activity
and improving sleep habits were given. Patients in CG received only written
information for a healthy lifestyle. At the end of 6 months, 88.8 % of
participants completed the study. On the basis of intention-to-treat analysis,
both MDG and MLG showed greater weight reduction and higher adherence to MD
compared with the CG (all P<0.05) at the end of intervention. In addition, MLG
increased vigorous exercise compared with the other two study groups (P<0.001)
and mid-day rest/naps compared with CG (P=0.04). MLG showed significant
improvements in ALT levels (i.e. ALT<40 U/l (P=0.03) and 50 % reduction of ALT
levels (P=0.009)) and liver stiffness (P=0.004) compared with CG after adjusting
for % weight loss and baseline values. MDG improved only liver stiffness compared
with CG (P<0.001) after adjusting for the aforementioned variables. Small changes
towards the Mediterranean lifestyle, along with weight loss, can be a treatment
option for patients with NAFLD.
PMID- 29947323
TI - Effectiveness of a home fortification programme with multiple micronutrients on
infant and young child development: a cluster-randomised trial in rural Bihar,
India.
AB - Research demonstrates the importance of nutrition for early brain development.
Few studies have examined the effectiveness of multiple micronutrient powders
(MNP) on child development. This study examined the impacts of home fortification
with MNP on motor and mental development, executive function and memory of
children living in Bihar. This two-arm cluster-randomised effectiveness trial
selected seventy health sub-centres to receive either MNP and nutrition
counselling (intervention) or nutrition counselling alone (control) for 12
months. Front-line health workers delivered the intervention to all households in
study communities with a child aged 6-18 months. Data were collected using cross
sectional surveys at baseline and endline by selecting households from
intervention (baseline, n 2184; endline, n 2170) and control (baseline, n 2176;
endline, n 2122) communities using a two-stage cluster-randomised sampling
strategy. Children in the intervention group had a significantly larger
improvement from baseline to endline compared with those in the control group on
scores for motor and mental development (Cohen's d, motor=0.12; 95 % CI 0.03,
0.22; mental=0.15; 95 % CI 0.06, 0.25). Greater impacts of MNP on motor and
mental development were observed in children from households with higher
stimulation scores at baseline compared with those with lower stimulation
(Cohen's d, motor=0.20 v. 0.09; mental=0.22 v. 0.14; P interaction<0.05). No
significant treatment differences were seen for executive function or memory.
Home fortification with MNP through the existing health infrastructure in Bihar
was effective in improving motor and mental development and should be considered
in combination with other child development interventions such as stimulation.
PMID- 29947324
TI - Patterns of beverage consumption and risk of CHD among Mexican adults.
AB - CHD is becoming an increasing priority worldwide, as it is one of the main causes
of death in low- and middle-income countries lately. This study aims to evaluate
the association between beverage consumption patterns and the risk of CHD among
Mexican adult population. We performed a cross-sectional analysis using data from
6640 adults participating in the Health Workers' Cohort Study. Factor analysis
was performed to identify beverage patterns using sex-specific Framingham
prediction algorithms to estimate CHD risk. The prevalence of moderate to high
CHD risk was 17.8 %. We identified four major beverage consumption patterns,
which were categorised as alcohol, coffee/tea, soft drinks and low-fat milk. We
observed a lower risk of CHD (OR=0.61; 95 % CI 0.46, 0.80; and OR=0.58; 95 % CI
0.43, 0.79, respectively) among participants in the upper quintile of alcohol or
low-fat milk consumption compared with those in the bottom quintile. In contrast,
a higher consumption of soft drinks was positively associated with CHD risk
(OR=1.64; 95 % CI 1.21, 2.20) when compared with other extreme quintiles.
Finally, coffee/tea consumption was not significantly associated with CHD risk.
Our findings suggest that a beverage pattern characterised by a higher intake of
sugar-sweetened beverages may be associated with an increased risk of CHD among
the Mexican adult population, whereas patterns of moderate alcohol intake and low
fat milk may be associated with a reduced risk.
PMID- 29947325
TI - Time to address the double inequality of differences in dietary intake between
Scotland and England.
AB - Geographical disparities in health outcomes have been evident across the UK for
decades. Recent analysis on the dietary differences between Scotland and England
that might go some way to explain these health differences is limited. This study
aimed to assess whether, and to what degree, aspects of diet and nutrition differ
between Scottish and English populations, specifically between those with similar
household incomes. A period of 12 years of UK food purchase data (2001-2012) were
pooled and used to estimate household-level consumption data for Scotland and
England. Population mean food consumption and nutrient intakes were estimated,
adjusting for known confounders (year, age of household reference person, age
they left full-time education and income). Comparison was also made within
equivalised income quintiles. Analysis showed that the foods and nutrients that
should be increased in the diet (highlighted in the Scottish Dietary Goals) were
lower in Scotland than in England (e.g. fruit and vegetables 267 g/d; 99 % CI
259, 274 v. 298 g/d; 99 % CI 296, 301), P<0.001). Similarly, foods and drinks
linked with poor health outcomes were higher in Scotland. These regional
inequalities in diet were even more pronounced in the lower-income groups (e.g.
red and processed meat consumption in the lowest-income quintile was 65 g/d; 99 %
CI 61, 69 in Scotland v. 58 g/day; 99 % CI 57, 60 in England, P<0.001, but
similar in the highest-income quintile (58 g/d; 99 % CI 54, 61 v. 59 g/d; 99 % CI
58, 60, respectively). A poorer diet in Scotland compared with England,
particularly among disadvantaged groups, may contribute to differences in excess
mortality between countries.
PMID- 29947326
TI - Use of an electronic malnutrition screening tool in a hospital setting: effects
on knowledge, attitudes and perceived practices of healthcare staff.
AB - Malnutrition risk screening is essential for the adequate identification and
treatment of malnourished hospitalised patients. The aim of this study was to
determine the effect of the use of an electronic malnutrition screening tool on
the knowledge, attitudes and perceived practices (KAP) of a pool of nurses,
nurses' aides and physicians. A controlled study using a pre-test-post-test
design was carried out in two Austrian hospitals. The hospital that was assigned
to the intervention group used the Graz malnutrition screening tool. The hospital
that was assigned to the control group received no intervention. To collect data,
a questionnaire was filled out by the study participants at baseline (T0) and 1
month after the implementation (T1) to assess KAP. All data were analysed using
descriptive statistics, chi 2 tests, Wilcoxon signed-rank tests and Student's t
tests. A total of 269 nurses, nurses' aides and physicians participated in the
study and completed the questionnaires at T0, and 190 people at T1. The sum score
for the KAP questionnaire changed significantly after the implementation of the
malnutrition screening tool in the intervention group (P<0.001), but not in the
control group. The use of a valid and reliable malnutrition screening tool
effectively improved the KAP of healthcare staff. The KAP described here are
essential for providing successful nutritional care in malnourished patients, and
improving these factors may result in improved patient outcomes. To attain these
outcomes, stakeholders, as well as members of all professions involved in
multidisciplinary nutritional care, must invest significant efforts.
PMID- 29947327
TI - Low 10-year reproducibility of glycaemic index and glycaemic load in a
prospective cohort study.
AB - When relating glycaemic index (GI) and glycaemic load (GL) to health outcomes,
many prospective cohort studies assess the nutritional exposure only once in
time, that is, at the start of the study, presuming a stability in nutritional
consumption during the course of the study. The aim of this study is to
investigate the reproducibility of GI and GL. This is a prospective cohort study
in which 562 middle-aged Belgian adults noted all foods and drinks consumed
during 3 d in 2002 and 2012. GI and GL were calculated after reference tables.
The Pearson correlation coefficients between 2002 and 2012 were 0.27 for GI and
0.41 for GL. For GI, 33 % of the participants remained in the same quintile
between 2002 and 2012, whereas 31 % moved to a non-adjacent quintile. For GL,
this was 34 and 28 %, respectively. The lowest and the highest quintiles of GI
were the most stable, with 40 and 44 % of the participants staying in the same
quintile. This was only 22 % for the fourth quintile. The same tendency was
present for GL - that is, the most extreme quintiles were the most stable. This
study shows 10-year correlation coefficients for GI and GL below 0.50. Multiple
nutritional assessments and limiting the analysis to the extreme quintiles of GI
and GL will limit a possible misclassification in the prospective cohort studies
owing to the low reproducibility.
PMID- 29947328
TI - Pressure garment to prevent abnormal scarring after burn injury in adults and
children: the PEGASUS feasibility RCT and mixed-methods study.
AB - BACKGROUND: Eleven million people suffer a fire-related injury worldwide every
year, and 71% have significant scarring. Pressure garment therapy (PGT) is a
standard part of burn scar management, but there is little evidence of its
clinical effectiveness or cost-effectiveness. OBJECTIVE: To identify the barriers
to, and the facilitators of, conducting a randomised controlled trial (RCT) of
burn scar management with and without PGT and test whether or not such a trial is
feasible. DESIGN: Web-based surveys, semistructured individual interviews, a
pilot RCT including a health economic evaluation and embedded process evaluation.
SETTING: UK NHS burns services. Interviews and the pilot trial were run in seven
burns services. PARTICIPANTS: Thirty NHS burns services and 245 staff provided
survey responses and 15 staff participated in individual interviews. Face-to-face
interviews were held with 24 adult patients and 16 parents of paediatric patients
who had undergone PGT. The pilot trial recruited 88 participants (57 adults and
31 children) who were at risk of hypertrophic scarring and were considered
suitable for scar management therapy. Interviews were held with 34 participants
soon after recruitment, with 23 participants at 12 months and with eight staff
from six sites at the end of the trial. INTERVENTIONS: The intervention was
standard care with pressure garments. The control was standard care comprising
scar management techniques involving demonstration and recommendations to
undertake massage three or four times per day with moisturiser, silicone
treatment, stretching and other exercises. MAIN OUTCOME MEASURES: Feasibility was
assessed by eligibility rates, consent rates, retention in allocated arms,
adherence with treatment and follow-up and completion of outcome assessments. The
outcomes from interview-based studies were core outcome domains and barriers to,
and facilitators of, trial participation and delivery. RESULTS: NHS burns
services treat 2845 patients per annum (1476 paediatric and 1369 adult) and use
pressure garments for 6-18 months, costing L2,171,184. The majority of staff
perceived a need for a RCT of PGT, but often lacked equipoise around the research
question and PGT as a treatment. Strong views about the use of PGT have the
potential to influence the conduct of a full-scale RCT. A range of outcome
domains was identified as important via the qualitative research: perceptions of
appearance, specific scar characteristics, function, pain and itch, broader
psychosocial outcomes and treatment burden. The outcome tools evaluated in the
pilot trial did not cover all of these domains. The planned 88 participants were
recruited: the eligibility rate was 88% [95% confidence interval (CI) 83% to
92%], the consent rate was 47% (95% CI 40% to 55%). Five (6%) participants
withdrew, 14 (16%) were lost to follow-up and 8 (9%) crossed over. Adherence was
as in clinical practice. Completion of outcomes was high for adult patients but
poorer from parents of paediatric patients, particularly for quality of life.
Sections on range of movement and willingness to pay were found to be challenging
and poorly completed. LIMITATIONS: The Brisbane Burn Scar Impact Profile appears
more suitable in terms of conceptual coverage than the outcome scales that were
used in the trial but was not available at the time of the study. CONCLUSIONS: A
definitive RCT of PGT in burn scar management appears feasible. However, staff
attitudes to the use of pressure garments may lead to biases, and the provision
of training and support to sites and an ongoing assessment of trial processes are
required. FUTURE WORK: We recommend that any future trial include an in-depth
mixed-methods recruitment investigation and a process evaluation to account for
this. TRIAL REGISTRATION: Current Controlled Trials ISRCTN34483199. FUNDING: This
project was funded by the National Institute for Health Research (NIHR) Health
Technology Assessment programme and will be published in full in Health
Technology Assessment; Vol. 22, No. 36. See the NIHR Journals Library website for
further project information.
PMID- 29947329
TI - From vesicle to cytosol.
AB - Drugs called bisphosphonates are used to treat a range of bone diseases, but how
do they reach the enzymes that are their target?
PMID- 29947330
TI - A mechanical system for tensile testing of supported films at the nanoscale.
AB - Standard tensile tests of materials are usually performed on freestanding
specimens. However, such requirement is difficult to implement when the materials
of interest are of nanoscopic dimensions due to problems related to their
handling and manipulation. In the present paper, a new device is presented for
tensile testing of thin nanomaterials, which allows tests to be carried out on
specimens initially deposited onto a macroscopic pre-notched substrate. On
loading, however, no substrate effects are introduced, allowing the films to be
freely stretched. The results obtained from a variety of thin metal or polymeric
films are very promising for the further development of this technique as a
standard method for nanomaterial mechanical testing.
PMID- 29947331
TI - Pseudo-spin skyrmions in the phase diagram of cuprate superconductors.
AB - Topological states of matter are at the root of some of the most fascinating
phenomena in condensed matter physics. Here we argue that skyrmions in the pseudo
spin space related to an emerging SU(2) symmetry enlighten many mysterious
properties of the pseudogap phase in under-doped cuprates. We detail the role of
the SU(2) symmetry in controlling the phase diagram of the cuprates, in
particular how a cascade of phase transitions explains the arising of the
pseudogap, superconducting and charge modulation phases seen at low temperature.
We specify the structure of the charge modulations inside the vortex core below T
c, as well as in a wide temperature region above T c, which is a signature of the
skyrmion topological structure. We argue that the underlying SU(2) symmetry is
the main structure controlling the emergent complexity of excitations at the
pseudogap scale T *. The theory yields a gapping of a large part of the anti
nodal region of the Brillouin zone, along with q = 0 phase transitions, of both
nematic and loop currents characters.
PMID- 29947332
TI - Efficacy of probiotics: clinical and microbial parameters of halitosis.
AB - BACKGROUND & AIM: Halitosis is defined as an offensive breath odour of whatever
source and therefore may affect a person's social interactions. Intra-oral
halitosis is a result of bacterial activity. Therefore, probiotics may offer an
appropriate and biological solution as a part of the therapy of intra-oral
halitosis. The aim of this systematic review was to study the effect of the
administration of probiotics alone or as an adjunct to other treatments on the
level of halitosis as measured by volatile sulphur compound (VSC) levels,
organoleptic scores (ORG) or hydrogen sulphide, methyl mercaptan and dimethyl
sulphide levels. In addition, the effect of probiotic usage on oral microbial
composition was summarised. METHODS: The MEDLINE-PubMed and Embase databases were
searched up to September 2017 with language restricted to English. Eligible
papers were selected according to pre-set criteria; the data was extracted and
analysed descriptively. RESULTS: The search resulted in 1104 original research
articles and a final six were selected as being eligible including 129 subjects.
These studies used different detection methods and combinations thereof to
measure halitosis. Five studies were randomised placebo-controlled clinical
trials of which two studies reported a significant reduction in ORG between
probiotic and placebo groups, and two studies on the basis of total VSC levels.
The two studies reporting a significant improvement in ORG did not find an
improvement in total VSC levels. Three studies included a microbiological
assessment. In these three studies, the probiotic strain was detected at the end
of the treatment period, but no detailed data was reported on the abundance of
the strain before and after the treatment period. CONCLUSIONS: Probiotics may be
beneficial in treating intra-oral halitosis. However, due to limited data and the
heterogeneity of the studies, the efficacy of probiotics remains unclear. Studies
with more subjects and standardised protocols need to be designed.
PMID- 29947333
TI - Carbon composite materials with ordered mesoporous structures from straw:
hydrothermal preparation and application as catalysts.
AB - Carbon-based composite materials with tunable, ordered mesoporous structures were
prepared via the hydrothermal carbonization/soft-template method, with nickel
nitrate as the doping source, straw as the carbon source, and F127 as the soft
template. By adjusting the additive amounts of Ni and F127, the mesoporous
structure was controllable, and results were obtained that varied from an
irregular stripe-like hexagonal, a regular stripe-like hexagonal, mixed hexagonal
and cubic, to cubic. With a specific surface area in the range of 339-963 m2 g-1,
the percentage of mesoporous structures increased from 39.6% to 58.3%. Ni doped
into the carbon skeletons existed in the form of metallic Ni and nickel oxide.
Increased amounts of nickel nitrate for doping as well as F127 is beneficial for
the generation of metallic Ni during the preparation process. The average
particle diameter of Ni decreased when the Ni-doped content was increased, and
all the average particle sizes were less than 10 nm after F127 was added. The
Nim/CSFn catalyst demonstrated high catalytic activity when used for the
hydrogenation reaction of p-nitrophenol (PNP) to p-aminophenol (PAP). The
conversion of PNP reached 98.79%, and the selectivity for PAP reached 89.6% for
Ni2.0/CSF1.5, with a corresponding apparent rate constant of 1.56 * 10-3 S-1,
apparent activation energy of 41.86 kJ mol-1, and with the added benefit that the
catalyst could be separated and recycled by applying an external magnetic field.
PMID- 29947334
TI - Length measurement and spatial orientation reconstruction of single nanowires.
AB - The accurate determination of the geometrical features of quasi one-dimensional
nanostructures is mandatory for reducing errors and improving repeatability in
the estimation of a number of geometry-dependent properties in nanotechnology. In
this paper a method for the reconstruction of length and spatial orientation of
single nanowires (NWs) is presented. Those quantities are calculated from a
sequence of scanning electron microscope (SEM) images taken at different tilt
angles using a simple 3D geometric model. The proposed method is evaluated on a
collection of SEM images of single GaAs NWs. It is validated through the
reconstruction of known geometric features of a standard reference calibration
pattern. An overall uncertainty of about 1% in the estimated length of the NWs is
achieved.
PMID- 29947335
TI - Intersubband absorption in GaN nanowire heterostructures at mid-infrared
wavelengths.
AB - In this paper, we study intersubband characteristics of GaN/AlN and
GaN/Al0.4Ga0.6N heterostructures in GaN nanowires structurally designed to absorb
in the mid-infrared wavelength region. Increasing the GaN well width from 1.5 to
5.7 nm leads to a red shift of the intersubband absorption from 1.4 to 3.4 MUm.
The red shift in larger quantum wells is amplified by the fact that one of the
GaN/AlN heterointerfaces (corresponding to the growth of GaN on AlN) is not sharp
but rather a graded alloy extending around 1.5-2 nm. Using AlGaN instead of AlN
for the same barrier dimensions, we observe the effects of reduced polarization,
which blue shifts the band-to-band transitions and red shifts the intersubband
transitions. In heavily doped GaN/AlGaN nanowires, a broad absorption band is
observed in the 4.5-6.4 MUm spectral region.
PMID- 29947336
TI - Influence of medium viscosity and intracellular environment on the magnetization
of superparamagnetic nanoparticles in silk fibroin solutions and 3T3 mouse
fibroblast cell cultures.
AB - Biomedical applications based on the magnetic properties of superparamagnetic
iron oxide nanoparticles (SPIONs) may be altered by the mechanical attachment or
cellular uptake of these nanoparticles. When nanoparticles interact with living
cells, they are captured and internalized into intracellular compartments.
Consequently, the magnetic behavior of the nanoparticles is modified. In this
paper, we investigated the change in the magnetic response of 14 nm magnetic
nanoparticles (Fe3O4) in different solutions, both as a stable liquid suspension
(one of them mimicking the cellular cytoplasm) and when associated with cells.
The field-dependent magnetization curves from inert fluids and cell cultures were
determined by using an alternating gradient magnetometer, MicroMagTM 2900. The
equipment was adapted to measure liquid samples because it was originally
designed only for solids. In order to achieve this goal, custom sample holders
were manufactured. Likewise, the nuclear magnetic relaxation dispersion profiles
for the inert fluid were also measured by fast field cycling nuclear magnetic
relaxation relaxometry. The results show that SPION magnetization in inert fluids
was affected by the carrier liquid viscosity and the concentration. In cell
cultures, the mechanical attachment or confinement of the SPIONs inside the cells
accounted for the change in the dynamic magnetic behavior of the nanoparticles.
Nevertheless, the magnetization value in the cell cultures was slightly lower
than that of the fluid simulating the viscosity of cytoplasm, suggesting that
magnetization loss was not only due to medium viscosity but also to a reduction
in the mechanical degrees of freedom of SPIONs rotation and translation inside
cells. The findings presented here provide information on the loss of magnetic
properties when nanoparticles are suspended in viscous fluids or internalized in
cells. This information could be exploited to improve biomedical applications
based on magnetic properties such as magnetic hyperthermia, contrast agents and
drug delivery.
PMID- 29947337
TI - Vaccination with Live Attenuated L. Major and TLR4 Agonist Promotes a Th1 Immune
Response and Induces Protection against L. Major Infection in BALB/c Mice.
AB - BACKGROUND: Toll like receptors play a major role in immune responses against
Leishmania parasites. OBJECTIVE: To evaluate the efficacy of vaccination with
live attenuated L. major and TLR4 agonist in protection against L. major
infection. METHODS: Attenuated L. major was prepared by continuous sub-culturing
of the parasite. A total of 90 mice were assigned to 9 groups including 6 groups
of BALB/c (G1-6) and 3 groups (G7-9) of C57BL/6 mice. Group 1 was the control
groups, group 2 received the wild-type L. major promastigotes, group 3 the
attenuated line, group 4 the TLR4 agonist, group 5 the wild-type L. major and
TLR4 agonist, and group 6 the attenuated line along with TLR4 agonist. Group 7
was control, group 8 received wild-type L. major and group 9 the wild-type along
with TLR4 agonist. Vaccinated mice were then challenged with wild-type of L.
major. Lesion size, parasite burden, and the expression levels of IL-4, IFN
gamma, IL-2, 1L-17A, IL-10, TGF-beta and TLR4 were evaluated before the challenge
while parasite burden and lesion size were evaluated. RESULTS: Vaccinated mice
with a TLR4 agonist or attenuated L. major plus TLR4 agonist produced the highest
levels of IFN-gamma, IL-2, and IL-17A. Post-challenge analysis revealed that mice
vaccinated with the attenuated line along with TLR4 agonist displayed the lowest
lesion size and parasite load. These mice developed a predominant Th1 immune
response. CONCLUSION: Vaccination with the attenuated L. major along with TLR4
agonist promotes a Th1-mediated immune response which leads to the protection of
BALB/c mice against L. major infection.
PMID- 29947338
TI - Anti-inflammatory Effects of PMX205 in Mouse Macrophage Periodontitis Model.
AB - BACKGROUND: C5a receptor antagonist PMX205 is a synthetic hexapeptide capable of
blocking C5a-C5a receptor (C5aR) axis by simulating C5a active C-terminal amino
acid residues. This hexapeptide presents good anti-inflammatory effects in a
series of inflammation models. The anti-inflammatory effect of PMX205 on
periodontitis is yet to be fully fathomed. OBJECTIVE: To examine the anti
inflammatory effects of PMX205 on RAW264.7 mouse macrophages exposed to gingipain
extracts and Porphyromonas gingivalis (P. gingivalis). METHODS: MTT assay was
carried out so as to specify the cytotoxicity of PMX205. RAW264.7 cells were co
cultured in vitro with gingipain extracts or P. gingivalis to simulate the
periodontitis inflammatory milieu. Real-time quantitative PCR, ELISA and Griess
assay were performed in order to detect tumor necrosis factor-alpha (TNF-alpha),
IL-6, IL-23, nitric oxide (NO), IL-10, transforming growth factor-beta1 (TGF
beta1), andarginase-1 (Arg-1). Furthermore, phagocytosis assay was done to
evaluate the phagocytic capacity of RAW 264.7 cells. Finally, western blot
analysis was conducted to evaluate myeloid differentiation factor 88 (MyD88).
RESULTS: PMX205 increased the expression levels of bacteriostatic substances (NO
and IL-23) and anti-inflammatory cytokines (TGF-beta1, IL-10 and Arg-1); however,
it reduced the expression levels of proinflammatory cytokines TNF-alpha and IL-6
once RAW 264.7 macrophages were stimulated via gingipain extracts or P.
gingivalis. In addition, PMX205 promoted the macrophage phagocytosis and down
regulated protein expression of MyD88. CONCLUSION: PMX205 has recognizable anti
inflammatory effects in RAW 264.7 cell inflammation model, a finding which
probably opens doors to future investigations on new targets for the prevention
and treatment of chronic periodontitis.
PMID- 29947340
TI - Association between KIR Genes and Efficacy of Treatment of HBeAg-Positive Chronic
Hepatitis B Patients with Entecavir.
AB - : Entecavir (ETV) is commonly used to treat chronic hepatitis B (CHB) in China.
However, certain percentages of e-Antigen (HBeAg) positive CHB patients do not
respond to ETV therapy. OBJECTIVE: To investigate whether the killer
immunoglobulin-like receptor (KIR) genes were associated with seroconversion in
HBeAg positive CHB responder patients treated with ETV. METHODS: Polymerase chain
reaction with sequence-specific primers (PCR-SSP) method was performed to
genotype KIR genes in 200 healthy controls and 198 HBeAg-positive CHB patients
which 59 were defined as the complete response group (CRG) to the treatment with
ETV and 139 were defined as null or partial response group (NPRG). RESULTS: The
frequencies of KIR2DS2 and KIR2DS3 were significantly higher (P=0.030,
OR=1.57,95%CI=2.36-1.05 and P=0.018, OR=1.773,95%CI=2.77-1.13, respectively),
while, the frequencies of KIR2DL3, KIR2DS1 and KIR3DS1 were significantly lower
(P=0.038, OR=0.525, 95%CI=0.96-0.29,and P=0.031, OR=0.640, 95%CI =0.95-0.43, and
P=0.035, OR=0.641, 95%CI=0.96-0.43, respectively) in HBeAg-positive CHB patients
than those in healthy controls. The frequency of KIR2DS3 gene was significantly
higher in NPRG than that in CRG (P=0.018, OR=0.402, 95%CI=0.83-0.20). The
frequencies of KIR2DL3 and KIR3DS1 genes were significantly higher in CRG than
those in NPRG (P=0.019, OR=3.625, 95%CI=10.83-1.21 and P=0.041, OR=1.949,
95%CI=3.65-1.04, respectively). CONCLUSION: Patients with KIR2DS3 might have
negative responses to anti-HBV therapy with ETV and patients with KIR2DL3 and
KIR3DS1 might have advantage in the therapy with ETV.
PMID- 29947339
TI - HLA Class I and Class II Genes Distribution of the Iranian Sistanis.
AB - BACKGROUND: The high polymorphism in the human leukocyte antigen (HLA) genes can
be used as an identity of individuals to compare with other populations. This
extreme polymorphism in the HLA system is accountable for the differences in
alleles and haplotypes among ethnic groups, populations, and the inhabitants of
many regions. OBJECTIVE: To define the frequency of HLA alleles and haplotypes
among the Sistanis, Sistani/Zaboli population in Iran. METHODS: In this study,
genotyping of class I (A, B, C) and class II HLA (DRB1, DQA1, DQB1) loci were
determined in 90 unrelated Iraninan Sistani people and the results were compared
with 474,892 HLA chromosomes from a diverse worldwide population. RESULTS: The
highest frequently observed alleles in this study were A*02:01, B*35:01, C*12:03,
C*06:02, DRB1*11, DQA1*05:05, and DQB1*03:01. Furthermore, the most frequent 3
locus haplotypes were A*02:01-B*50:01*C*06:02, DRB1*11-DQB1*03:01-DQA1*05:05, and
A*02:01-B*50:01-DRB1*07. The most occurring 4-locus haplotypes were A*02:01
B*50:01-C*06:02-DRB1*07 and A*02:01-B*50:01-DRB1*07-DQB1*02:01. A*02:01-B*50:01
C*06:02-DRB1*07-DQB1*02:01 and A*02:01-B*50:01-C*06:02-DRB1*07-DQB1*02:01
DQA1*02:01 were determined to be the predominant 5- and 6-locus haplotypes,
respectively. The heat maps and multiple correspondence analyses based on the
frequency of HLA alleles showed that Sistanis share a common genetic inheritance
with other Iranian ethnic groups such as the people from Yazd and Fars except
some differences with Baluchis, Iranian Jews, Lurs of Kohgiluyeh/Buyerahmad, and
Arabs of Fars, which may arise from the admixture of these groups or with foreign
subgroups over centuries, and also a close relatedness with some European
populations. CONCLUSION: These data could be useful for finding better donor
matches for organ transplantation among Sistanis or other related Iranian ethnic
groups, epidemiological studies of HLA-associated diseases, handling HLA genomics
and mapping the migration pattern of different ethnic group.
PMID- 29947341
TI - Hemin Induces the Activation of NLRP3 Inflammasome in N9 Microglial Cells.
AB - BACKGROUND: Hemin is an important sterile component that induces a
neuroinflammatory response after intracerebral hemorrhage, in which NLRP3
inflammasome activation has also proved to be involved. Although microglial
activation acts as a key contributor in the neuroinflammatory response, the
relationship between hemin and NLRP3 in microglia remains poorly understood.
OBJECTIVE: To investigate whether or not hemin regulates microglia-mediated
secondary injury through activating the NLRP3/caspase-1 signaling pathway in
microglia. METHODS: In this study, N9 microglial cells were treated with hemin,
and subsequently used to detect the production of caspase-1 p10 and NLRP3
inflammasome assembly. An ELISA was subsequently performed to measure the
secretion of IL-1beta. RESULTS: It was found that the production of activated
caspase-1 was dose- and time-dependent with regards to hemin. Moreover, hemin was
observed to be capable of inducing the assembly of the NLRP3 inflammasome without
any increase in IL-1beta. Similarly, the supernatant of hemin-treated primary
microglial cells did not increase in IL-1beta secretion. Furthermore, hemin
induced NLRP3 inflammasome activation did not significantly affect pyroptosis.
CONCLUSION: Hemin is a potential sterile danger signal molecule that can induce
inflammasome activation without directly mediating inflammation damage on
microglia.
PMID- 29947342
TI - Identification of hnRNP C1/C2 as an Autoantigen in Patients with Behcet's
Disease.
AB - BACKGROUND: Ribonucleoproteins particles that form the spliceosomes are among the
most frequently targeted molecules of the autoimmune response. In the last few
years, autoantibodies against all A/B hnRNP proteins have been found in the sera
of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE),
mixed connective tissue disease (MCTD), and serve as diagnostic markers for
several rheumatic diseases. However, the functional role of hnRNP C1/C2 in
autoimmune diseases is still not clearly understood. OBJECTIVE: To identify hnRNP
C1/C2 as an autoantigen in patients with Behcet's Disease (BD). METHODS: First,
HaCaT and EA.hy926 cells were cultured and RNA was extracted. Second,
amplification of the corresponding gene by RT-PCR, cloning, and purification
techniques was applied to acquire the recombinant protein hnRNP C1/C2. Third, the
target protein band was excised from gel electrophoresis, digested with trypsin,
and analyzed by (MALDI-TOF/). Finally, Western blotting and ELISA were performed
to verify the immunoreactivity of BD serum with recombinant hnRNPC1/C2. RESULTS:
Results demonstrated that the reactivity of BD serum against recombinant hnRNP
C1/C2 protein was significantly higher as compared to healthy control (P<0.001).
CONCLUSION: hnRNP C1/C2 can be considered as a self antigen which might be
involved in BD pathology in Hans Chinese population.
PMID- 29947343
TI - Increased Levels of AIM2 and Circulating Mitochondrial DNA in Type 2 Diabetes.
AB - BACKGROUND: Chronic inflammation has critical role in Type 2 diabetes (T2D), in
which IL-1beta contributes in insulin resistance and beta cell dysfunction. The
activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the
release of active form of IL-1beta. OBJECTIVE: To evaluate AIM2 expression and
activation as well as circulating mtDNA levels in T2D patients. METHODS: AIM2
expression was analyzed by flow cytometry, it's activity was assessed by
measuring in vitro release of IL-1beta induced by Poly (dA:dT), and mtDNA copy
number was determined by quantitative real-time polymerase chain reaction.
RESULTS: Increased percent of AIM2+ cells were detected in monocytes from
patients with T2D. Moreover, increased levels of IL-1beta in monocytes cultures
from T2D patients compared to healthy controls were observed. Also, association
between AIM2+ cells and hyperglycemia (r=0.4385, P=0.0095) and triglycerides
levels (r=0.5112, P=0.002) and waist-hip ratio (r=0.4710, P=0.0049) were
detected. Likewise, the mtDNA copy number was augmented in T2D patients compared
to control group. The mtDNA copies number was associated with body mass index
(r=0.4231, P=0.0008) and TNF-alpha levels (r=0.5231, P=0.0005). In addition,
increased levels of IL-12p70, TNF-a, IL-10, IL-6, IL-8 and IL-1beta were detected
in a serum from T2D patients. CONCLUSION: These results suggest the involvement
of AIM2 and mtDNA in the inflammatory process seen in T2D.
PMID- 29947344
TI - The Relationship between Plasma Levels of Interleukin-6, Multiple Organ
Dysfunction and Mortality in Orthopedic Patients.
AB - BACKGROUND: Interleukin 6 (IL-6) functions as both a pro-inflammatory cytokine
and an anti-inflammatory cytokine. OBJECTIVE: To evaluate the levels of IL-6 in
patients with multiple organ dysfunction syndrome (MODS). METHODS: Level of IL-6
was assessed and recorded for 14 days subsequent to the injury in 161 multiple
trauma patients. MODS were diagnosed using Marshal Score. Injury Severity Scoring
(ISS) was measured for all patients. RESULTS: The results of this study indicated
that there was a significant relationship between the level of IL-6 and ISS on
the first and second days post trauma (P=0.0001). The high level of IL-6 on the
second day post trauma was associated with high mortality rate. CONCLUSION: Our
study suggests the second day as the golden time for measuring the serum levels
of IL-6. These findings warn us to take more health care actions in patients with
higher serum levels of IL-6 on the second day.
PMID- 29947346
TI - Corrigendum: Diabetic cornea wounds produce significantly weaker electric signals
that may contribute to impaired healing.
AB - This corrects the article DOI: 10.1038/srep26525.
PMID- 29947347
TI - Corrigendum: Maintained larval growth in mussel larvae exposed to acidified under
saturated seawater.
AB - This corrects the article DOI: 10.1038/srep23728.
PMID- 29947345
TI - Analysis of Appendiceal Neoplasms on 3544 Appendectomy Specimens for Acute
Appendicitis: Retrospective Cohort Study of a Single Institution.
AB - BACKGROUND Appendiceal neoplasms are rare and generally determined in
appendectomy specimens for acute appendicitis. Depending on a tumor's
histopathology and size, appendectomy or right hemicolectomy are the surgical
treatment options. Adenocarcinomas, mucinous neoplasms, goblet cell carcinoids
and neuroendocrine tumors are the types of the primary appendiceal neoplasm
histopathology. In this study, we aimed to determine the incidence of appendiceal
neoplasms in an acute appendicitis cohort. Also, histopathological distributions,
demographic data, preoperative radiological diagnosis, and intraoperative
findings were revealed for analysis, retrospectively. MATERIAL AND METHODS
Between October 2011 and September 2017, 3554 appendectomies were performed for
acute appendicitis in Bezmialem University Hospital, Istanbul Turkey. The medical
records of these consecutive 3554 patients were evaluated retrospectively. After
the histopathological analysis of the appendectomy specimens, a total of 28
patients were detected as having appendiceal neoplasm including appendiceal
adenocarcinoma, low grade mucinous neoplasia, and appendiceal neuroendocrine
tumors. RESULTS Appendiceal neoplasms were determined in 28 out of 3554 acute
appendicitis patients with an incidence of 0.78%. According to the
histopathological types, 3 of the cases (10.7%) were appendiceal adenocarcinoma,
8 of the cases (28.5%) were low grade mucinous neoplasia, and 17 of the cases
(60.8%) were neuroendocrine tumors. The overall incidence of the appendiceal
neuroendocrine tumors was 0.48%. CONCLUSIONS The information obtained from our
study suggests that pathological examination of the specimen may not be necessary
if there is no doubt according to preoperative radiological diagnosis and/or
intraoperative findings of the surgeon.
PMID- 29947348
TI - A Systematic Review of Interventions for Sexual Well-Being in Women With
Gynecologic, Anal, or Rectal Cancer.
AB - PROBLEM IDENTIFICATION: Treatments for cancer in the lower pelvis often cause
lasting effects on women's sexual well-being. The purpose of this review is to
describe interventions to improve sexual well-being in gynecologic, anal, or
rectal cancer survivors. LITERATURE SEARCH: This review follows the PRISMA
(Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009
checklist and guidelines. A literature search was conducted using PubMed,
CINAHL(r), PsycINFO, and Cochrane Library. DATA EVALUATION: Articles were
original intervention research studies of women treated for gynecologic, anal, or
rectal cancer and included sexual well-being outcomes. Study characteristics were
extracted and compared in a table for analysis and synthesis. SYNTHESIS: Of the
16 included studies, 1 focused on genitourinary rehabilitation, 12 focused on
psychoeducational interventions, and 3 focused on combination interventions. Most
interventions reported at least one positive sexual well-being outcome.
Intervention format, delivery, dose, and outcome variables varied widely.
IMPLICATIONS FOR RESEARCH: Preliminary efficacy and feasibility of interventions
are promising, but larger studies designed to discern optimal content, delivery
format, dose, and timing are needed.
PMID- 29947349
TI - Symptom Clusters in Patients With Pancreatic Cancer Undergoing Surgical
Resection: Part I.
AB - OBJECTIVES: To describe patient-reported symptoms and symptom clusters in
patients with pancreatic cancer (PC) undergoing surgical resection. SAMPLE &
SETTING: 143 patients with stage II PC undergoing surgical resection alone or
with subsequent adjuvant chemoradiation or chemotherapy were recruited to
participate in a nested, longitudinal, exploratory study through convenience
sampling techniques from Thomas Jefferson University Hospital, a National Cancer
Institute-designated cancer center. METHODS & VARIABLES: The Functional
Assessment in Cancer Therapy-Hepatobiliary questionnaire was used to assess 17 PC
symptoms preoperatively and at three, six, and nine months postoperatively.
Exploratory and confirmatory factor analyses were used to identify symptom
clusters. RESULTS: Fatigue, trouble sleeping, poor appetite, trouble digesting
food, and weight loss were consistently reported as the most prevalent and severe
symptoms. Sixteen distinct symptom clusters were identified within nine months of
surgery. Four core symptom clusters persisted over time. IMPLICATIONS FOR
NURSING: Findings may be used to provide anticipatory patient and family guidance
and to inform clinical assessments of symptoms and symptom clusters in this
population.
PMID- 29947350
TI - Symptom Clusters in Patients With Pancreatic Cancer Undergoing Surgical
Resection: Part II.
AB - OBJECTIVES: To explore the relationship between 16 symptom clusters (SCs),
clinical and demographic influencing factors, and clinical outcomes over time in
patients with pancreatic cancer (PC) undergoing surgical resection. SAMPLE &
SETTING: 143 patients with stage II PC undergoing surgical resection were
recruited to participate in this longitudinal, exploratory study conducted at
Thomas Jefferson University Hospital, a National Cancer Institute-designated
cancer center. METHODS & VARIABLES: Quality of life was measured
preoperatively and at three, six, and nine months postoperatively. Statistical
methods included simple linear and Cox proportional hazard regression. RESULTS:
Preoperative pain was significantly associated with the pain-gastrointestinal SC,
and preoperative worry was significantly associated with the mood SC. The
strongest negative association with emotional well-being across all study time
points was found with the preoperative mood SC. The insomnia-digestive problems
SC and the nutritional problems SC demonstrated a trend toward poor survival.
IMPLICATIONS FOR NURSING: Findings provide evidence that preoperative worry and
pain are associated with SC severity and that SCs may have a detrimental effect
on quality of life and survival in patients with PC undergoing surgical
resection.
PMID- 29947351
TI - Social Support and Health-Related Quality of Life Among Gay and Bisexual Men With
Prostate Cancer.
AB - OBJECTIVES: To describe social support patterns of gay and bisexual men with
prostate cancer (GBMPCa) and how social support is associated with prostate
cancer outcomes. SAMPLE & SETTING: A cross-sectional online survey with 186
GBMPCa recruited from a national cancer support group network. METHODS &
VARIABLES: Descriptive statistics of social support and linear regression of
social support on general and prostate cancer-specific quality of life (QOL).
Social support and health-related QOL were assessed generally and specific to
prostate cancer. RESULTS: Participants primarily relied on partners or husbands,
gay and bisexual friends, chosen family, and men from support groups for support.
The most common types of support received were informational and emotional social
support. Low general social support was significantly associated with worse
prostate cancer symptom bother and general mental QOL. Wanting more social
support was significantly associated with worse prostate cancer-specific and
general QOL. IMPLICATIONS FOR NURSING: Clinicians should be aware of the
different social support networks and needs of GBMPCa and refer them to relevant
support groups to improve QOL.
PMID- 29947352
TI - Hidden Patients, Hidden Partners: Prostate Cancer Care for Gay and Bisexual Men.
AB - Research and clinical practice efforts to improve outcomes for men with prostate
cancer have largely ignored the unique social support circumstances of gay and
bisexual men (GBM), leading to a gap in the literature regarding social support
needs of GBM with prostate cancer. Capistrant et al. (2018) addressed this gap by
using survey data to examine social support and quality of life in GBM with
prostate cancer. Their work provides insights about how nurses can make changes
through research and clinical care to better treat GBM with prostate cancer.
PMID- 29947353
TI - Clinical Characteristics of Children and Adolescents Undergoing Hematopoietic
Cell Transplantation Who Develop Oral Mucositis.
AB - OBJECTIVES: To describe the clinical characteristics of children and adolescents
undergoing hematopoietic cell transplantation (HCT) who develop oral mucositis.
SAMPLE & SETTING: 45 patients who underwent HCT from July 2015 to May 2016 at
St. Jude Children's Research Hospital in Memphis, Tennessee. METHODS &
VARIABLES: Clinical factors were described as transplantation type, mucositis
severity or grade, mucositis duration, days to engraftment, total parenteral
nutrition (TPN) support, IV opioid pain management use during mucositis, positive
blood or oral cultures, and length of hospitalization, then compared across
mucositis grade. RESULTS: 24 patients had grade 3 or greater mucositis onset from
day -3 to day 9 of transplantation; of these, 23 required IV opioid medication to
treat mucosal pain. Patients with mucositis grade 3 or greater were more likely
to have undergone an allogeneic transplantation, receive TPN, have documented
positive blood or oral cultures, and have longer hospitalizations than those with
low-grade mucositis. IMPLICATIONS FOR NURSING: Nurses are in a unique position to
propose and administer interventions to prevent and alleviate symptoms of
mucositis.
PMID- 29947354
TI - Taking Photos of Presentations: Dissemination or Distraction?
AB - I am sure that all of us have been to conferences where, sitting in the audience,
the person next to or in front of you reaches up with his or her phone or other
device and snaps a photo of whatever is on the screen. Or perhaps you are the one
doing just that. I understand the reasons for this; we want to remember the
information being presented and/or we want to take that nugget of information
back to our colleagues at work. But is this an appropriate thing to do?
PMID- 29947355
TI - Use of Virtual Reality to Distract From Pain and Anxiety.
AB - OBJECTIVES: To determine the effects of a virtual reality intervention on pain
and anxiety in patients undergoing a bone marrow aspiration and biopsy procedure.
SAMPLE & SETTING: 97 adults in an outpatient cancer center in the midwestern
United States. METHODS & VARIABLES: In this quasiexperimental study,
participants were assigned to either the experimental group (use of virtual
reality goggles) or the control group (standard treatment). Vital signs, pain,
and anxiety were measured before and after the procedure. T tests and chi-square
tests were used to compare the two groups based on demographic data, pain,
anxiety, and total amount of medication used during the procedure. RESULTS:
Participants who wore virtual reality goggles during a bone marrow aspiration and
biopsy procedure did not experience a statistically significant decrease in pain
and anxiety. However, the experimental and control groups showed a decrease in
pain and anxiety levels from pre- to postprocedure. IMPLICATIONS FOR NURSING:
Virtual reality goggles may be a feasible, noninvasive alternative to traditional
pharmacologic treatment. The cost of any intervention would need to be
considered. Virtual reality should be researched and adapted to benefit patients
in appropriate settings.
PMID- 29947356
TI - Distress and Supportive Care Needs of Ethnically Diverse Older Adults With
Advanced or Recurrent Cancer.
AB - OBJECTIVES: To assess the prevalence of supportive care needs (SCNs) and distress
and to describe relationships among these and patient characteristics for
ethnically diverse older adults with advanced or recurrent cancer. SAMPLE &
SETTING: Cross-sectional survey in five outpatient oncology clinics in an urban
academic medical center involving 100 participants receiving cancer care in an
economically challenged community. METHODS & VARIABLES: The supportive care
framework for cancer care guided this study, and participants completed the SCN
Survey Short Form 34 and the Distress Thermometer. Study variables are cancer
diagnosis, gender, helping to raise children, number of comorbid diseases, race
or ethnicity, treatment status, and zip code. RESULTS: Clinically meaningful
distress was found in about a third of patients. Distress was not affected by
race or ethnicity. Many ethnically diverse older patients with advanced or
recurrent cancer report distress and SCNs; those with high distress are more
likely to report multiple SCNs. IMPLICATIONS FOR NURSING: Nursing assessment of
patient SCNs and distress is integral to establishing individualized patient
centered care plans and to delivering optimal care.
PMID- 29947357
TI - Children's Experiences of Cancer Care: A Systematic Review and Thematic Synthesis
of Qualitative Studies.
AB - PROBLEM IDENTIFICATION: Improvements in pediatric cancer survival have increased
interest in the experiences of children undergoing treatment; however, no review
of the qualitative literature describing these experiences has been conducted.
LITERATURE SEARCH: Databases were searched from January 2000 to January 2016 for
qualitative studies describing the experience of children with cancer aged 18
years or younger. DATA EVALUATION: Two reviewers assessed abstracts for relevance
and rated reporting comprehensiveness. Participant quotations and descriptions of
participants' comments and behaviors were coded. Coded data were pooled to
provide a thematic synthesis. SYNTHESIS: 51 studies were included. Five themes
were identified. IMPLICATIONS FOR RESEARCH: Results provide data related to the
experience of children with cancer that can inform practice changes and research
activities aimed at enhancing quality of life.
PMID- 29947358
TI - Pressure Pain Phenotypes in Women Before Breast Cancer Treatment.
AB - OBJECTIVES: To explore associations between quantitative sensory testing (QST)
and pretreatment pain, physical, and psychological characteristics in women with
breast cancer. SAMPLE & SETTING: 41 women with treatment-naive stage 0-III
breast cancer at the University of Michigan Comprehensive Cancer Center in Ann
Arbor. METHODS & VARIABLES: Participants completed self-report surveys and
QST within the month before breast surgery. Pressure pain thresholds (PPTs) were
measured bilaterally at each trapezius with a manual QST algometer. PPT values
were split, yielding low, moderate, and high pain sensitivity subgroups. Subgroup
self-reported characteristics were compared using Spearman's correlation, chi
square, and one-way analysis of variance. RESULTS: Lower PPT (higher sensitivity)
was associated with higher levels of pain interference and maladaptive pain
cognitions. The high-sensitivity group reported higher pain severities,
interference, and catastrophizing and lower belief in internal locus of pain
control than the low-sensitivity group. IMPLICATIONS FOR NURSING: Individualized
interventions for maladaptive pain cognitions before surgery may reduce pain
sensitivity and the severity of chronic pain developed after surgery.
PMID- 29947359
TI - Factors Associated With Medication Beliefs in Patients With Cancer: An
Integrative Review.
AB - PROBLEM IDENTIFICATION: Medication beliefs are linked to medication adherence in
cancer treatment. Oral cancer treatments are increasing, making patients
responsible for self-managing medication at home. LITERATURE SEARCH: A literature
search was performed using CINAHL(r), PubMed, and PsycINFO. Included studies were
published in English from 2000-2017 and examined medication beliefs among
participants aged 18 years or older who were prescribed cancer medication. DATA
EVALUATION: Articles were organized by study design, how medication beliefs were
measured, and whether psychometric testing was evaluated. Articles were scored to
indicate rigor of medication belief measurements. Themes of factors associated
with medication beliefs were compiled. SYNTHESIS: The review represented several
cancer and cancer medication types. Various methods were used to elicit
medication beliefs. Medication beliefs influence decisions to initiate or
continue cancer medications, and those beliefs are multifaceted. Nurses have a
critical role in evaluating and supporting facilitative medication beliefs.
IMPLICATIONS FOR RESEARCH: Nurses can address medication beliefs and clarify
treatment misconceptions. Understanding factors influencing medication beliefs
can inform future interventions to improve adherence and symptom management.
PMID- 29947363
TI - Abeta under stress: the effects of acidosis, Cu2+-binding, and oxidation on
amyloid beta-peptide dimers.
AB - In light of the high affinity of Cu2+ for Alzheimer's Abeta1-42 and its ability
to subsequently catalyze the formation of radicals, we examine the effects of
Cu2+ binding, Abeta oxidation, and an acidic environment on the conformational
dynamics of the smallest Abeta1-42 oligomer, the Abeta1-42 dimer. Transition
networks calculated from Hamiltonian replica exchange molecular dynamics (H-REMD)
simulations reveal that the decreased pH considerably increased the beta-sheet
content, whereas Cu2+ binding increased the exposed hydrophobic surface area,
both of which can contribute to an increased oligomerization propensity and
toxicity.
PMID- 29947364
TI - Diazonium salt chemistry for the design of nano-textured anti-icing surfaces.
AB - Aryl diazonium salts have emerged as a new generation of robust surface modifiers
for a wide range of applications. However, their use for creating anti-icing
surfaces has never been investigated so far. We fill this gap by modifying nano
textured copper surfaces with aryl diazonium salts, bearing low surface energy
end groups, leading to efficient anti-icing properties.
PMID- 29947365
TI - Black TiO2-based nanoprobes for T1-weighted MRI-guided photothermal therapy in
CD133 high expressed pancreatic cancer stem-like cells.
AB - At present, transmembrane glycoprotein CD133 highly expressed pancreatic cancer
stem cells (PCSCs), with the features of chemotherapeutic/radiotherapeutic
resistance and exclusive tumorigenic potential, are considered as the primary
cause of metastasis and recurrence in pancreatic cancer, and therefore are an
effective target in the disease treatment. Furthermore, with the launch of
precision medicine, multifunctional nanoprobes have been applied as an efficient
strategy for the magnetic resonance imaging (MRI)-guided photothermal therapy
(PTT) of pancreatic cancer. In this research, with the aim of achieving precise
MRI-guided PTT in CD133 highly expressed PCSCs, novel bTiO2-Gd-CD133mAb
nanoprobes were designed and successfully prepared by loading Gd-DOTA and CD133
monoclonal antibodies on black TiO2 nanoparticles. It was very interesting to
find that the r1 relaxivity value of the nanoprobes was 34.394 mM-1 s-1, about
7.5 times that of commercial Magnevist (4.5624 mM-1 s-1), which indicates that
the nanoprobes have good potential as MRI T1 contrast agents with excellent
performance. Herein, CD133 highly expressed PANC-1 cells were selected and
verified as PCSCs model. In vitro experiments demonstrated that the nanoprobes
exhibited active-targeting ability in PANC-1 cells, and consequently could
specially enhance T1-weighted MR imaging and 808 nm near-infrared (NIR)-triggered
PTT efficiency in the PCSCs model. Our study not only provides a new strategy for
the effective treatment of pancreatic cancer and its' stem cells, but also
further broadens the application of black TiO2 in the field of cancer
theranostics.
PMID- 29947366
TI - Measuring viscosity inside mesoporous silica using protein-bound molecular rotor
probe.
AB - Fluorescence spectroscopy of protein-bound molecular rotors Cy3 and Cy5 is used
to monitor the effective viscosity inside the pores of two types of mesoporous
silica (SBA-15 and MCF) with pore diameters between 8.9 and 33 nm. The ratio of
the peak intensities is used to measure viscosity independently of solvent
polarity, and the response of the lipase-bound dyes is calibrated using
glycerol/water mixtures (no particles). The two dyes are either attached to the
same protein or separate proteins in order to investigate potential effects of
energy transfer (FRET) on the fluorescence properties, when using them as
reporter dyes. The effective viscosity inside the pores at infinite protein
dilution is one order of magnitude higher than in bulk water, and the effect of
protein concentration on the measured viscosity indicates a stronger effect of
protein-protein interactions in the pores than in similarly concentrated protein
solutions without particles. In MCF-particles with octyl-groups covalently
attached to the pore walls, a more efficient uptake of the lipase resulted in
FRET between the protein-bound dyes even if the two dyes were attached to
different proteins. In contrast to the unmodified particles the intensity-ratio
method could therefore not be used to measure the viscosity, but the presence of
FRET in itself indicates that octyl-protein interactions lead to a non-homogenous
protein distribution in the pores. The dye labels also report a less polar pore
environment as sensed by the proteins through a redshift in the dye emission.
Both observations may help in understanding the higher efficiency of lipase
immobilization in octyl-modified particles.
PMID- 29947367
TI - Isotope effects on the spin dynamics of single-molecule magnets probed using muon
spin spectroscopy.
AB - Muon spin relaxation (MUSR) experiments on a single-molecule magnet enriched in
different Dy isotopes detect unambiguously the slowing down of the zero field
spin dynamics for the non-magnetic isotope. This occurs in the low temperature
regime dominated by quantum tunnelling, in agreement with previous ac
susceptibility investigations. In contrast to the latter, however, MUSR is
sensitive to all fluctuation modes affecting the lifetime of the spin levels.
PMID- 29947368
TI - Dual electrical switching permeability of vesicles via redox-responsive self
assembly of amphiphilic block copolymers and polyoxometalates.
AB - Electro-responsive vesicles were demonstrated based on an amphiphilic block
copolymer PEO114-b-P(DCH-Ru)n and an inorganic nanoparticle polyoxometalate
H3PMo12O40 (PMo12) via electrostatic interactions. After undergoing
electrochemical reactions, vesicle membranes allow the migration of electrolyte
ions and release of loaded cargos.
PMID- 29947370
TI - Trace water mediated growth of oriented single-crystalline mesoporous metal
organic frameworks on gold nanorods.
AB - Here we report, for the first time, the growth of single-crystalline mesoporous
MOFs with well-controlled orientation on the surface of gold nanorods.
Importantly, it showed that trace amounts of water could induce the formation of
MOFs of different phases and shapes, which was critical for the synthesis of such
mesoporous heterostructures.
PMID- 29947369
TI - Chiral modulation of amyloid beta fibrillation and cytotoxicity by enantiomeric
carbon dots.
AB - Enantiomeric carbon dots (C-dots) synthesized from l-lysine or d-lysine, modulate
aggregation and cytotoxicity of amyloid beta-42 (Abeta42), the primary
constituent of the amyloid plaques associated with Alzheimer's disease. In
particular, l-Lys-C-dots dramatically remodeled Abeta42 secondary structure and
fibril morphologies, as well as inhibited Abeta42 cytotoxicity and membrane
interactions.
PMID- 29947371
TI - Central metal dependent modulation of induced-fit gas uptake in molecular
porphyrin solids.
AB - The induced-fit accommodation of a variety of gaseous molecules including non
polar molecules has been demonstrated in porphyrin-based supramolecular
architectures for the first time. Moreover, the gas uptake behaviour can be
modulated by changing the central cation of porphyrin.
PMID- 29947372
TI - Deep eutectic-water binary solvent associations investigated by vibrational
spectroscopy and chemometrics.
AB - Investigation of the behaviour of deep eutectic solvents (DESs) as novel green
solvents in the presence of other solvents is of great interest. In this study
the behaviour of a common natural DES, namely choline chloride-glycerol deep
eutectic solvent (GDES), was studied in the presence of water. A detailed study
of the association of the two solvents was performed by integration of two
vibrational spectroscopic methods (FTIR and Raman spectroscopy) followed by
multivariate analysis. Moreover, a binary mixture of glycerol (Gly) as one of the
liquid constituents of GDES and water was explored under the same conditions. A
quintuplet and ternary systems were resolved for GDES-water and Gly-water probes,
respectively, using multivariate analysis of global data (multi-technique and
multi-experiment data arrangements). The results confirmed that in the presence
of water the GDES showed different behaviour from its components. Therefore, a
DES can be introduced as an independent solvent with its unique properties. Also,
different H-bond interaction energies of GDES and its pure components in the
presence of water were shown by theoretical calculations based on a density
functional theory framework. To investigate the effects of water on the structure
of GDES, molecular dynamics (MD) simulations of GDES-water liquid mixtures were
performed at 0.9 mole fraction of water.
PMID- 29947373
TI - Reducing the toxicity of amphotericin B by encapsulation using methoxy
poly(ethylene glycol)-b-poly(l-glutamic acid-co-l-phenylalanine).
AB - Amphotericin B (AmB) is an antifungal drug used for serious fungal infections and
leishmaniosis. However, its clinical application is limited because of its high
toxicity. To resolve this problem, herein we loaded AmB into methoxy
poly(ethylene glycol)-b-poly(l-glutamic acid-co-l-phenylalanine) (mPEG-b-P(Glu-co
Phe)) nanoparticles (l-AmB) via electrostatic, hydrophobic and pi-pi
interactions. The l-AmB has excellent stability both in PBS and in plasma and
shows a remarkably reduced hemolysis (17.1 +/- 1.5%, 6 h) compared to the free
AmB (94.2 +/- 5.3%, 6 h). The nephrotoxicity of l-AmB is significantly lower than
that of free AmB. The maximum tolerance dose (MTD) of l-AmB is 3.0 mg kg-1, which
is 3.75 fold that of free AmB (MTD = 0.8 mg kg-1). The antimicrobial activity of
the conjugate was retained in vivo, with l-AmB proving to be a more protective
treatment for Aspergillus fumigatus infections in mice than AmB alone. These
indicate that l-AmB is a formulation of AmB with low side effects.
PMID- 29947374
TI - Unusual rearrangement of an N-heterocyclic carbene via a ring-opening and ring
closing process.
AB - The reaction of a pentadentate NHC ligand precursor with Ni(OAc)2.4H2O or
Pd(OAc)2 in the presence of a base yields four-coordinate square-planar Ni(ii)
and Pd(ii) complexes with an unusual ligand generated in situ. A series of
experimental studies point to a ring-opening and ring-closing process via novel C
N bond cleavage and formation.
PMID- 29947375
TI - Synthesis of zero-valent iron nanoparticles via laser ablation in a formate ionic
liquid under atmospheric conditions.
AB - Transition metal nanoparticles (NPs) are promising materials for use as catalysts
in many processes, although they are easily oxidized under ambient conditions. In
this communication, a novel synthetic method is proposed for producing zero
valent iron (Fe) NPs by laser ablation under atmospheric conditions using the
reducing properties of a formate-based ionic liquid solvent. The valence state of
Fe was confirmed using X-ray absorption near edge structure (XANES) spectroscopy.
The Fe NPs adopt a face centered cubic structure after synthesis, which gradually
transforms to a body centered cubic structure after one month. The method can be
extended to the synthesis of other transition metal NPs that are easily oxidized.
PMID- 29947376
TI - CO2-Triggered microreactions in liquid marbles.
AB - On-demand initiation of dual- and multi-component microreactions inside liquid
marbles (LMs) was developed by coalescing contacting patchy LMs containing
separate reagents through CO2-induced wetting transition of the interface between
the LMs.
PMID- 29947378
TI - Probing the electric double-layer capacitance in a Keggin-type polyoxometalate
ionic liquid gated graphene transistor.
AB - A variety of device applications has been proposed using polyoxometalate-based
ionic liquids. However, the assembly of large polyoxometalate ions on surfaces
and the associated interfacial properties are not well understood, particularly
since the assembly is influenced by steric effects and stronger ion-ion
interactions. In this study, graphene transistors gated with a polyoxometalate
based ionic liquid were probed with in situ Raman spectroscopy and charge
transport studies. The ionic liquid comprised Cu-substituted lacunary Keggin
anions, [PW11O39Cu]5-, which were surrounded by tetraoctyl ammonium cations,
(C32H68N)+. The application of gate voltage caused these ions to assemble at the
interface with graphene, which resulted in a shift of the Fermi level of the
graphene monolayer grown on a copper foil. The shift was determined by the
quantum capacitance, Cq, of graphene in series with the electric-double layer
capacitance. Estimates of the electric-double layer thickness, spatial density of
the ions and temporal rate of the assembly of the electric double-layer were
obtained. This study provides insights into the microscopic understanding of the
electric double-layer formation at the graphene interface.
PMID- 29947377
TI - Three-stage pH-switchable organic chromophores with large nonlinear optical
responses and switching contrasts.
AB - Three-stage pH-switchable organic second-order nonlinear optical (SO NLO)
chromophores are synthesized and characterized by wavelength-dependent linear and
nonlinear spectroscopy. The chromophores exhibit huge SO NLO responses in their
"on" stages, and large switching contrasts between adjacent stages in both SO NLO
response and fluorescence quantum yield, with moreover different "on/off"
sequences for closely related compounds.
PMID- 29947379
TI - Growth of nanodroplets on a still microfiber under flow conditions.
AB - Surface droplets in the microscale are of great interest for their relevance in
broad droplet-based technologies. Derived from the Ouzo effect, the solvent
exchange process is a simple bottom-up approach to produce surface nano-/micro
droplets by the nucleation and growth mechanism. The oil oversaturation pulse is
created as a good solvent (ethanol) for the oil displaced by a poor solvent
(water) in the flow cell. In this work, we investigated the formation of surface
droplets on a one-dimensional substrate (a single hydrophobic fiber with a
diameter of 10 MUm) in a flow. The droplet growth on the microfiber is enhanced
as the fiber is perpendicular to the external flow direction, due to the coupled
effects between the droplet formation and the local flow. On the other hand, the
droplet growth exhibits different growth dynamics when the fiber is placed
parallel to the external flow direction. The general trend that surface droplets
grow faster on a fiber at higher flow rates is consistent with the situation on
planar substrates. The coupled interactions between the growing droplets and the
local flow conditions during the solvent exchange process were further revealed
in the simulations. The findings from this work will be valuable for the design
and utilization of the solvent exchange process to produce surface nanodroplets
on a microfiber under flow conditions and thus broaden the droplet-based
application fields.
PMID- 29947380
TI - Enhancement of field electron emission in topological insulator Bi2Se3 by Ni
doping.
AB - Nanostructures of bismuth selenide (Bi2Se3), a 3D topological insulator material,
and nickel (Ni) doped Bi2Se3 samples were prepared by a hydrothermal method to
explore the field emission properties. An enrichment in the field electron
emission (FE) properties in terms of the threshold and turn-on field values of
Bi2Se3 and Ni doped Bi2Se3 nanostructures was measured at a base pressure of ~1 *
10-8 mbar. Using the background of the Fowler-Nordheim (FN) theory a field
enhancement factor (beta) of 5.7 * 103 and a threshold field value of 2.5 V MUm-1
for 7.5% Ni doped Bi2Se3 were determined by investigating the J-E plot of the FE
data. The value of beta is three times higher than that of pure Bi2Se3 confirming
the superior FE properties. The emission current was found to be very stable with
the property of long standing durability as a negligible amount of variation was
observed when measured at a constant value of 5 mA for 3 hours. The experimental
results signify many opportunities for potential applications of Ni doped Bi2Se3
as a source of electrons in scanning as well as transmission electron microscopy,
flat panel displays and as an X-ray generator, etc.
PMID- 29947381
TI - Analysis of transition state stabilization by non-covalent interactions in
organocatalysis: application of atomic and functional-group partitioned symmetry
adapted perturbation theory to the addition of organoboron reagents to
fluoroketones.
AB - This work seeks to apply symmetry-adapted perturbation theory (SAPT) to the
recent study of Hoveyda and co-workers [K. A. Lee et al., Nat. Chem. 2016, 8,
768] where an allyl addition to a ketone became enantioselective when the ketone
was fluorinated. Through the application of atomic SAPT (A-SAPT) and functional
group SAPT (F-SAPT), the non-covalent interactions between specific atoms and
functional groups in the transition states associated with the fluoroketone
reactions can be quantified. Our A-SAPT analysis confirms that a HF contact
thought to enhance stereoselectivity shows a strong preference for one of the
transition states leading to the experimentally observed product enantiomer.
Other key atom-atom contacts invoked to rationalize relative transition state
energies are also found to behave as expected based on chemical intuition and
contact distances. On the other hand, hypothesized steric clashes between
substrate phenyl or ortho-methyl phenyl groups and the catalyst are not supported
by F-SAPT computations, and indeed, these are actually favorable pi-pi
interactions.
PMID- 29947383
TI - The stabilization mechanism and size effect of nonpolar-to-polar crystallography
facet tailored ZnO nano/micro rods via a top-down strategy.
AB - A simple and efficient top-down strategy, the chemical vapor etching method, is
reported for synthesizing corrugated ZnO nano/micro rods (NRs). The stabilization
mechanism of this unique nanostructure has been determined through a combination
of aberration-corrected field emission scanning electron microscopy, high
resolution transmission electron microscopy, and first-principles calculations.
The experimental data are in good agreement with the theoretical calculations,
and a remarkable nonpolar-to-polar surface faceting transition is demonstrated.
The corrugated-shaped structure results from the remarkable stability of the
defect-induced reconstructions (O vacancy, Zn-Zn dimer), which makes the high
index polar {303[combining macron]1} and {101[combining macron]1[combining
macron]} planes lower in energy compared to the nonpolar {101[combining macron]0}
plane. Based on the results of first-principles surface calculations, a general
formula is established to provide an accurate description of the unusual size
effect of the length of the corrugated unit vs. the NR diameter, and it also
offers direct explanations for certain experimental observations. The present
study deepens our atomic-level understanding of the detailed structure and
stability of polar surface decorated corrugated ZnO NRs, and points to a viable
path towards designing polar-stable wurtzite structures.
PMID- 29947384
TI - Cyanide-isocyanide isomerization: stability and bonding in noble gas inserted
metal cyanides (metal = Cu, Ag, Au).
AB - The internal isomerization, MNC <-> MCN (M = Cu, Ag, Au), is investigated through
quantum chemical computations. CuNC and AgNC are shown to be neither
thermochemically nor kinetically stable against transformation to MCN. The free
energy barrier (DeltaG?) for AuNC is somewhat considerable (7.1 kcal mol-1),
indicating its viability, particularly at low temperature. Further, the Ng
inserted analogues, MNgCN (M = Cu, Ag, Au; Ng = Xe, Rn) turn out to be
thermochemically stable with respect to all possible dissociation channels but
for two two-body dissociation channels, viz., MNgCN -> Ng + MCN and MNgCN -> Ng +
MNC, which are connected to the internal isomerization processes, MNgCN -> NgMCN
and MNgCN -> NgMNC, respectively. However, they are kinetically protected by
substantial DeltaG? values (11.8-15.4 kcal mol-1 for Cu, 9.8-13.6 kcal mol-1 for
Ag, and 19.7-24.7 kcal mol-1 for Au). The pathways for such internal conversion
are explored in detail. A thorough inspection of the bonding situation of the
studied molecules, employing natural bond order, electron density, adaptive
natural density partitioning, and energy decomposition analyses indicates that
the M-Ng bonds in MNgCN and Ng-C bonds in AuNgCN can be represented as an
electron-shared covalent bond. For the other Ng-C bonds, although an ionic
description is better suited, the degree of covalent character is also
substantial therein.
PMID- 29947382
TI - A predictive model for the diffusion of a highly non-ideal ternary system.
AB - Diffusion plays a central part in many unit operations. The Maxwell-Stefan model
is the dominant model for both gaseous and liquid diffusion. However, it was
developed from the kinetic theory of gases, raising the question of whether it
can be extended to non-ideal liquid systems. The dynamic fluctuation model is an
alternative model based on the Cussler theory and predicts a smaller
thermodynamic influence relative to the linear influence of the Maxwell-Stefan
model due to dynamic concentration fluctuations. Since the dynamic fluctuation
model, which uses the scaling factor alpha, had improved performance relative to
the Maxwell-Stefan model for a wide range of binary systems, it is postulated
that this improved performance should also be observed for a ternary system. In
this work, the dynamic molecular fluctuation model was extended to a highly non
ideal ternary system, using the same scaling factor alpha, through matrix
manipulation. Using self-diffusion data measured by NMR, mutual diffusion
predictions of the developed model and the Maxwell-Stefan model were compared to
experimental mutual diffusion data of the partially miscible system
ethanol/toluene/n-decane. It is demonstrated that the dynamic fluctuation model
gives improved predictions relative to the Maxwell-Stefan approach, consistent
with previous observations on binary systems, showing that the reduced
thermodynamic influence of the dynamic fluctuation model is an improvement. In
addition, we show that the use of local mole fractions, to account for molecular
association, in both the dynamic fluctuation and Maxwell-Stefan models, results
in improved diffusion predictions for the ternary system. The results confirm
that the dynamic fluctuation model improves predictions of mutual diffusion in
liquid mixtures, suggesting a non-linear correction to the thermodynamic
correction factor. The results also suggest that that the key assumptions in the
Maxwell-Stefan model and its derivation, rooted in the kinetic theory of gases,
are not entirely accurate for highly non-ideal liquid systems. The optimum alpha
for the ternary system studied here is approximately 0.45, similarly to the
optimum alpha of 0.40 to 0.80 for a range of binary systems previously studied,
suggesting that the use of the alpha scaling factor, which is grounded in scaling
laws theory, is of general validity.
PMID- 29947385
TI - Nonstoichiometric oxides as a continuous homologous series: linear free-energy
relationship in oxygen exchange.
AB - A novel methodology for the analysis of oxygen exchange in practically important
nonstoichiometric oxides with mixed ionic electronic conductivity (MIEC) is
suggested. It is based on the fact that the kinetic and thermodynamic properties
of such oxides vary continuously with oxygen stoichiometry. This allows MIEC
oxides to be considered as a homologous series, with the difference that
traditional series are discrete in their chemical composition whereas MIEC oxides
are continuous in oxygen stoichiometry. Analysis of the relations between Gibbs
energies of reactions and activation barriers traditionally performed for
homologous series can be useful in studies of oxygen exchange in MIEC oxides. To
demonstrate the approach, thermodynamic and oxygen-exchange kinetics parameters
are measured as functions of oxygen nonstoichiometry delta for two perovskites,
SrCo0.8Fe0.2O3-delta and SrFeO3-delta, having metal-like and p-type
semiconducting conductivities, respectively. Both oxides are shown to obey linear
free energy relationships of the Bronsted-Evans-Polanyi form in spite of their
different types of electronic structures. The results open up new possibilities
for understanding the mechanism of the rate determining step of oxygen exchange
in MIEC oxides.
PMID- 29947386
TI - Zero-thermal-hysteresis magnetocaloric effect induced by magnetic transition at a
morphotropic phase boundary in Heusler Ni50Mn36Sb14-xInx alloys.
AB - With the development of magnetic refrigerant technology, magnetic substances with
a large magnetocaloric effect (MCE) and nearly zero thermal hysteresis are
desired. Although Ni-Mn based Heusler alloys have been found to produce large
MCEs and have attracted increasing attention recently, the occurrence of thermal
hysteresis accompanying MCE due to the nature of first-order phase transition
limits its applications with magnetic refrigeration. Up to now, an effective
theory or method to eliminate this thermal hysteresis is still lacking. Here, we
propose to utilize the feature of magnetic transition at the morphotropic phase
boundary (MPB) to eliminate thermal hysteresis and thus design a MPB-involved
phase diagram in Heusler alloys of Ni50Mn36Sb14-xInx (x = 0-14). As theoretically
expected, the magnetic transition at MPB really yields a MCE with a negligible
thermal hysteresis (~0 K) and the refrigerant capacity arrives at a maximum value
of 108.2 J kg-1 at the composition of x = 9. Our findings provide an effective
way to design large MCE materials with zero thermal hysteresis.
PMID- 29947387
TI - An organocatalyst bound alpha-aminoalkyl radical intermediate for controlled
aerobic oxidation of iminium ions.
AB - A catalyst bound alpha-aminoalkyl radical intermediate from iminium is developed
to control its formation and reactivity with aerobic oxygen. The influence of the
catalyst was demonstrated via the ease of radical intermediate formation and its
subsequent reactivity, including the first catalyst-controlled enantioselective
aerobic oxidation with a chiral phosphite catalyst.
PMID- 29947388
TI - The effect of anions on noncovalent interactions in model clusters of chalcogen
containing (CH3)2X (X = O, S, Se) molecules.
AB - A computational study of F-(CH3)2XYF (X = O, S, Se; Y = F, H) triads, with F-
bound to the protons of the two methyl groups, found significant enhancement of
the XY interactions relative to the neutral (CH3)2XYF dyads, more so for the XF
than the XH interaction. A subsequent model study of anionic F-(CH3)2OYZ (YZ =
HF, CH3F, SiH3F, GeH3F, NF3, OF2, F2, ClF) triads revealed a similar enhancement
of all OY noncovalent interactions. The relative stabilities and associated
properties of the OY sigma-hole interactions were rationalized using the
electronegativity difference between O and Y. Very strongly bound Z-(CH3)2X-F2 (Z
= F, Cl, Br; X = S, Se) clusters were also predicted and involve interactions
between the anion Z-, Lewis base (CH3)2X and two F atoms sandwiching the central
X atom to form a nearly linear F-X-F axis.
PMID- 29947389
TI - Atomic hydrogen interactions with gas-phase coronene cations: hydrogenation
versus fragmentation.
AB - Sequential hydrogenation of polycyclic aromatic hydrocarbon (PAH) cations drives
a gradual transition from a planar to a puckered geometry and from an aromatic to
an aliphatic electronic structure. The resulting H-induced weakening of the
molecular structure together with the exothermic nature of the consecutive H
attachment processes can lead to substantial molecular fragmentation. We have
studied H attachment to gas-phase coronene cations in a radiofrequency ion trap
using tandem mass spectrometry. With increasing hydrogenation, C2Hi loss and
multifragmentation are identified as main de-excitation channels. To understand
the dependence of both channels on H-exposure time, we have simulated the
molecular stability and fragmentation channels of hydrogenated PAHs using a
molecular dynamics approach employing potential energies determined by a density
functional based tight binding method. As the coronene fragmentation patterns
depend on the balance between energy deposition by H-attachment and the extent of
cooling in between subsequent attachment processes, we investigate several
scenarios for the energy distribution of hydrogenated PAHs. Good agreement
between experiment and simulation is reached, when realistic energy distributions
are considered.
PMID- 29947390
TI - Harnessing electrostatic catalysis in single molecule, electrochemical and
chemical systems: a rapidly growing experimental tool box.
AB - Static electricity is central to many day-to-day practical technologies, from
separation methods in the recycling of plastics to transfer inks in photocopying,
but the exploration of how electrostatics affects chemical bonding is still in
its infancy. As shown in the Companion Tutorial, the presence of an appropriately
oriented electric field can enhance the resonance stabilization of transition
states by lowering the energy of ionic contributors, and the effect that follows
on reaction barriers can be dramatic. However, the electrostatic effects are
strongly directional and harnessing them in practical experiments has proven
elusive until recently. This tutorial outlines some of the experimental platforms
through which we have sought to translate abstract theoretical concepts of
electrostatic catalysis into practical chemical technologies. We move step-wise
from the nano to the macro, using recent examples drawn from single-molecule STM
experiments, surface chemistry and pH-switches in solution chemistry. The
experiments discussed in the tutorial will educate the reader in some of the
viable solutions to gain control of the orientation of reagents in that field;
from pH-switchable bond-dissociations using charged functional groups to the use
of surface chemistry and surface-probe techniques. All of these recent works
provide proof-of-concept of electrostatic catalysis for specific sets of chemical
reactions. They overturn the long-held assumption that static electricity can
only affect rates and equilibrium position of redox reactions, but most
importantly, they provide glimpses of the wide-ranging potential of external
electric fields for controlling chemical reactivity and selectivity.
PMID- 29947391
TI - Fine-tuning polyoxometalate non-linear optical chromophores: a molecular
electronic "Goldilocks" effect.
AB - A new aryl-imido polyoxometalate non-linear optical chromophore (POMophore) with
a diphenylamino donor group attains the highest betazzz, 0 value (196 * 10-30 esu
by Hyper-Rayleigh Scattering, HRS), and best transparency/non-linearity trade off
yet for such materials. Stark spectroscopic and DFT investigation of this
compound, plus NMe2 and carbazole analogues, show that its high performance
results from a combination of strongly dipolar electronic transitions, and strong
electronic communication across the pi-system.
PMID- 29947393
TI - An efficient t-BuOK promoted C3-chalcogenylation of indoles with dichalcogenides.
AB - A versatile and efficient method for the synthesis of 3-chalcogenyl-indoles from
indoles and dichalcogenides employing t-BuOK as a promoter at room temperature
has been achieved. The present protocol exhibited a broad functional group
tolerance. Diverse 3-sulfenyl- and 3-selenyl-indoles were rapidly obtained in
good to excellent yields with high regioselectivities. It is noteworthy that this
transformation was applicable to N-protected and N-unprotected indoles, allowing
N-deprotection and C3-chalcogenylation of indoles in one step.
PMID- 29947394
TI - Stabilized monolayer 1T MoS2 embedded in CoOOH for highly efficient overall water
splitting.
AB - The complicated synthesis procedure and the unstable nature of 1T MoS2 vastly
impede its practical application although it has shown a high performance for
many different applications. Herein, we have synthesized ultrastable 1T phase
MoS2 embedded in CoOOH by a facile one-pot strategy and achieved a high overall
water splitting activity. The amorphous CoOOH in this heterostructure not only
exhibits high oxygen evolution reaction activity, but also anchors and stabilizes
the 1T MoS2 as vertically aligned single layers. This novel method gives new
insight into developing stable and active atomically thin transition metal
dichalcogenide heterostructures.
PMID- 29947395
TI - Synthesis and characterisation of fluorescent aminophosphines and their
coordination to gold(i).
AB - Three novel fluorescent aminophosphine ligands have been synthesised that
incorporate napthyl (L1), pyrenyl (L2) and anthraquinone (L3) chromophores into
their structures. The ligands react with [AuCl(tht)] (tht = tetrahydrothiophene)
to give neutral complexes of the form [AuCl(L1-3)]. Solid state, X-ray
crystallographic data was obtained for the anthraquinone derivative, [AuCl(L3)],
and showed a distorted linear coordination geometry at Au(i). The packing
structure also revealed a number of intermolecular pi-pi interactions that
involve the anthraquinone and phenyl units of the aminophosphine ligand. 31P NMR
spectroscopic data revealed deltaP values of +42.2 (L1), +42.1 (L2) and +26.1
(L3) ppm, which shifted downfield upon coordination to Au(i) to +64.6, +64.7, and
+55.8 ppm, respectively. Supporting TD-DFT studies were able to reproduce the
structure and 31P NMR chemical shifts of [AuCl(L3)] as well as rationalise the
HOMO-LUMO compositions. Photophysical studies showed that the appended
fluorophore dominates the absorption and emission properties for the ligands and
complexes, with the anthraquinone derivatives showing visible emission at ca. 570
nm which was attributed to the intramolecular charge transfer character of the
phosphinoaminoanthraquinone fragment.
PMID- 29947396
TI - Towards personalised rapid label free miRNA detection for cancer and liver injury
diagnostics in cell lysates and blood based samples.
AB - Advances in prevention, diagnosis and therapy are coupled to innovation and
development of new medical tools, leading to improved patient prognosis. We
developed an automatic biosensor platform that could provide a non-invasive,
rapid and personalised diagnosis using nanomechanical cantilever sensors. miRNA
are involved in gene expression and are extractable biomarkers for multiple
diseases. We detected specific expression patterns of miRNA relevant to cancer
and adverse drug effects directly in cell lysates or blood based samples using
only a few microliters of sample within one hour. Specific miRNA hybridisation to
the upper cantilever surface induces physical bending of the sensor which is
detected by monitoring the position of a laser that reflects from the sensors
surface. Internal reference sensors negate environmental and nonspecific effects.
We showed that the sensitivity of label free cantilever nanomechanical sensing of
miRNA surpasses that of surface plasmon resonance by more than three orders of
magnitude. A cancer associated miRNA expression profile from cell lysates and one
associated with hepatocytes derived from necrotic liver tissue in blood-based
samples has been successfully detected. Our label free mechanical approach
displays the capability to perform in relevant clinical samples while also
obtaining comparable results to PCR based techniques. Without the need to
individually extend, amplify or label each target allowing multitarget analysis
from one sample.
PMID- 29947397
TI - Targeted imaging of the lysosome and endoplasmic reticulum and their pH
monitoring with surface regulated carbon dots.
AB - Organelles play crucial roles in cellular activities and the functions of
organelles are related greatly to the pH values, therefore, the bio-imaging of
targeted organelles and their related pH sensing is of great importance in
biological assays. Herein we report the fluorescence imaging of specific
organelles, i.e., lysosomes and endoplasmic reticulum, and their pH sensing with
surface regulated carbon dots (CDs). Carbon dots functionalized with amine groups
(ACDs) are first prepared by hydrothermal treatment of citric acid and urea, and
then laurylamine functionalized CDs (LCDs) are obtained via the conjugation of
laurylamine with ACDs. The as-prepared ACDs and LCDs provide clear and bright
imaging results for the lysosome and endoplasmic reticulum, respectively. The
subcellular targeting features of the two CDs are attributed to their surface
chemistries and cellular uptake pathways. Moreover, both the CDs are pH
responsive within a certain pH range, i.e., 4.0-5.4 for ACDs and 6.2-7.2 for
LCDs. The ACDs and LCDs are thus successfully applied to visualize the pH
fluctuations of the lysosome and endoplasmic reticulum in MCF-7 cells.
PMID- 29947399
TI - Electrochemical energy storage devices for wearable technology: a rationale for
materials selection and cell design.
AB - Compatible energy storage devices that are able to withstand various mechanical
deformations, while delivering their intended functions, are required in wearable
technologies. This imposes constraints on the structural designs, materials
selection, and miniaturization of the cells. To date, extensive efforts have been
dedicated towards developing electrochemical energy storage devices for
wearables, with a focus on incorporation of shape-conformable materials into
mechanically robust designs that can be worn on the human body. In this review,
we highlight the quantified performances of reported wearable electrochemical
energy storage devices, as well as their micro-sized counterparts under specific
mechanical deformations, which can be used as the benchmark for future studies in
this field. A general introduction to the wearable technology, the development of
the selection and synthesis of active materials, cell design approaches and
device fabrications are discussed. It is followed by challenges and outlook
toward the practical use of electrochemical energy storage devices for wearable
applications.
PMID- 29947400
TI - Tracking down protein-protein interactions via a FRET-system using site-specific
thiol-labeling.
AB - Forster resonance energy transfer is among the most popular tools to follow
protein-protein interactions. Although limited to certain cases, site-specific
fluorescent labeling of proteins via natural functions by means of chemical
manipulations can redeem laborious protein engineering techniques. Herein we
report on the synthesis of a heterobifunctional tag and its use in site-specific
protein labeling studies aiming at exploring protein-protein interactions. The
oxadiazole-methylsulfonyl functionality serves as a thiol specific warhead that
enables easy and selective installation of fluorescent labels through a
bioorthogonal motif. Mitogen activated protein kinase (MAPK14) and its substrate
mitogen activated protein kinase activated kinase (MAPKAP2) or its docking motif,
a 22 amino acid-long peptide fragment, were labeled with a donor and an acceptor,
respectively. Evolution of strong FRET signals upon protein-protein interactions
supported the specific communication between the partners. Using an efficient
FRET pair allowed the estimation of dissociation constants for protein-protein
and peptide-protein interactions (145 nM and 240 nM, respectively).
PMID- 29947401
TI - Second-order asymmetric transformation and its application for the practical
synthesis of alpha-amino acids.
AB - We report a discovery of a new rimantadine [1-(1-adamantyl)ethanamine]-derived
chiral ligand and its application for the preparation of alpha-amino acids using
the second-order asymmetric transformation approach. The operational ease of
experimental procedures coupled with excellent chemical yields and stereochemical
outcome suggests some potential synthetic generality of this approach.
PMID- 29947404
TI - A galvanic exchange process visualized on single silver nanoparticles via dark
field microscopy imaging.
AB - The study of the galvanic exchange (GE) mechanism is beneficial for designing and
developing new bimetallic nanocrystal structures with excellent bifunctional
catalytic properties. Herein, we have visually demonstrated a GE process by real
time monitoring of the reaction between silver nanoparticles (AgNPs) and Au3+ at
the single nanoparticle level using light scattering dark-field microscopy
imaging. The localized surface plasmon resonance (LSPR) scattering spectral
shifts of the AgNPs which reveal the Ag removal rate and Au deposition rate on
the surface of the AgNPs can be observed. Furthermore, a pixel meta three color
channel method has been introduced for analyzing the scattering light color
changes of plasmonic particles to reveal the kinetics of the atomic deposition
process on a single AgNP during GE, thus making the reaction kinetics of the GE
process directly observable. Therefore, this study provides an efficient and
promising approach for understanding the GE mechanism and exploiting its reaction
kinetics.
PMID- 29947406
TI - Catalytic alkylation reactions of weakly acidic carbonyl and related compounds
using alkenes as electrophiles.
AB - Catalytic alkylation reactions of weakly acidic carbonyl and related
pronucleophiles such as amides, esters, and sulfonamides with substituted alkenes
have been reported. In the presence of a strong Bronsted base catalyst system,
potassium hexamethyldisilazide and 18-crown-6 ether, the desired reactions
proceeded in high yields at ambient temperature with a wide substrate scope.
These are atom-economical catalytic alkylation reactions of carbonyl and related
compounds.
PMID- 29947408
TI - Nanofibrous scaffolds for biomedical applications.
AB - Tissue engineering is an emergent and very interesting research field, providing
potential solutions for a myriad of challenges in healthcare. Fibrous scaffolds
specifically have shown promise as an effective tissue engineering method, as
their high length-to-width ratio mimics that of extracellular matrix components,
which in turn guides tissue formation, promotes cellular adhesion and improves
mechanical properties. In this review paper, we discuss in detail both the
importance of fibrous scaffolds for the promotion of tissue growth and the
different methods to produce fibrous biomaterials to possess favorable and unique
characteristics. Here, we focus on the pressing need to develop biomimetic
structures that promote an ideal environment to encourage tissue formation. In
addition, we discuss different biomedical applications in which fibrous scaffolds
can be useful, identifying their importance, relevant aspects, and remaining
significant challenges. In conclusion, we provide comments on the future
direction of fibrous scaffolds and the best way to produce them, proposed in
light of recent technological advances and the newest and most promising
fabrication techniques.
PMID- 29947407
TI - Synthesis of hydrophobic insulin-based peptides using a helping hand strategy.
AB - The introduction of solid-phase peptide synthesis in the 1960s improved the
chemical synthesis of both the A- and B-chains of insulin and insulin analogs.
However, the subsequent elaboration of the synthetic peptides to generate active
hormones continues to be difficult and complex due in part to the hydrophobicity
of the A-chain. Over the past decade, several groups have developed different
methods to enhance A-chain solubility. Two of the most popular methods are use of
isoacyl dipeptides, and the attachment of an A-chain C-terminal pentalysine tag
with a base-labile 4-hydroxymethylbenzoic acid linker. These methods have proven
effective but can be limited in scope depending on the peptide sequence of a
specific insulin. Herein we describe an auxiliary approach to enhance the
solubility of insulin-based peptides by incorporating a tri-lysine tag attached
to a cleavable Fmoc-Ddae-OH linker. Incorporation of this linker, or "helping
hand", on the N-terminus greatly improved the solubility of chicken insulin A
chain, which is analogous to human insulin, and allowed for coupling of the
insulin A- and B-chain via directed disulfide bond formation. After formation of
the insulin heterodimer, the linker and tag could be easily removed using a
hydrazine buffer (pH 7.5) to obtain an overall 12.6% yield based on A-chain. This
strategy offers an efficient method to enhance the solubility of hydrophobic
insulin-based peptides as well as other traditionally difficult peptides.
PMID- 29947409
TI - A naked-eye fluorescent sensor for copper(ii) ions based on a naphthalene
conjugate Bodipy dye.
AB - A novel naphthalene-Bodipy dye (N-Bodipy) was designed, prepared and
characterized. N-Bodipy showed a selective and sensitive recognition toward
Cu(ii) ions as a fluorescent antenna group in acetonitrile/water over other metal
cations. The complexation between Cu(ii) ions and N-Bodipy gave a specific color
change as well as caused fluorescence quenching under long-wavelength light (365
nm). The remarkable quenching effect in fluorescence intensity centered at 538 nm
was only observed in the presence of copper(ii) ions. Moreover, the orange color
of N-Bodipy solution turned pale-yellow depending on the complexation effect in
daylight. The complex stoichiometry was determined using a Job's plot and it was
found to be 2 : 1 (ligand/metal). The binding constant was calculated with the
Benesi-Hildebrand equation to be 1.39 * 1010 M-1 and the detection limit was 1.28
MUM (LOD = 3alpha/slope, alpha is the standard deviation) for Cu(ii). The data
proved that the binding between N-Bodipy and Cu(ii) is chemically reversible.
PMID- 29947410
TI - Relating the structure factors of two-dimensional materials in planar and
spherical geometries.
AB - Scattering structure factors provide essential insight into material properties
and are routinely obtained in experiments, computer simulations, and theoretical
analyses. Different approaches favor different geometries of the material. In
case of lipid bilayers, scattering experiments can be performed on spherical
vesicles, while simulations and theory often consider planar membrane patches. We
derive an approximate relationship between the structure functions of such a
material in planar and spherical geometries. We illustrate the usefulness of this
relationship in a case study of a Gaussian material that supports both
homogeneous and microemulsion phases. Within its range of applicability, this
relationship enables a model-free comparison of structure factors of the same
material in different geometries.
PMID- 29947411
TI - Deletion of a global regulator LaeB leads to the discovery of novel polyketides
in Aspergillus nidulans.
AB - By disruption of LaeB, a global regulator recently characterized in Aspergillus
nidulans, eight cryptic compounds in the mutant were identified, including seven
polyketides and one NRPS-like product. Among the isolates, two phthalides and two
dibenzo[1,4]dioxins are new compounds, revealing that the genetic manipulation of
the global regulator represents a promising approach for the discovery of novel
natural products in fungi.
PMID- 29947413
TI - Adhesion and friction between glass and rubber in the dry state and in water:
role of contact hydrophobicity.
AB - We study the contact mechanics between 3 different tire tread compounds and a
smooth glass surface in water. We study both adhesion and sliding friction at low
sliding speeds. For 2 of the compounds the rubber-glass contact in water is
hydrophobic and we observe adhesion, and slip-stick sliding friction dynamics.
For one compound the contact is hydrophilic, resulting in vanishing adhesion, and
steady-state (or smooth) sliding dynamics. We also show the importance of
dynamical scrape, both on the macroscopic level and at the asperity level, which
reduces the water film thickness between the solids during slip. The experiments
show that the fluid is removed much faster from the rubber-glass asperity contact
regions for a hydrophobic contact than for a hydrophilic contact. We also study
friction on sandblasted glass in water. In this case all the compounds behave
similarly and we conclude that no dewetting occur in the asperity contact
regions. We propose that this is due to the increased surface roughness which
reduces the rubber-glass binding energy.
PMID- 29947414
TI - Kinetic evolution of DOPC lipid bilayers exposed to alpha-cyclodextrins.
AB - Cyclodextrins are cyclic oligosaccharides capable of forming inclusion complexes
with a variety of molecules, and as such have been recognized as a pharmaceutical
and biotechnological asset. Cyclodextrins are known to interact with the
components of cell membranes, and this correlates with a significant degree of
cytotoxicity. In this work, we report on the mechanism of degradation of a model
dioleoyl-phosphatidylcholine (DOPC) bilayer exposed to a solution with increasing
concentrations of alpha-cyclodextrins. By combining optical fluorescence
microscopy and quartz-crystal microbalance experiments, we study the evolution of
supported lipid bilayers (SLBs) and giant unilamellar vesicles (GUVs). The rate
of lipid removal is found to display a strong nonlinear dependence on the
cyclodextrin concentration. A mechanism involving lipid aggregates is proposed.
PMID- 29947415
TI - (2-Fluoroallyl)boronates: new reagents for diastereoselective 2
fluoroallylboration of aldehydes.
AB - A Pd-catalyzed borylation of 2-fluoroallyl chlorides with B2pin2 in the presence
of [(2-MeAll)PdCl]2/TMEDA or [(2-MeAll)Pd(IPr)Cl] was developed to afford (2
fluoroallyl)pinacolboronates with high Z-selectivity. The products proved to be
useful for anti-selective 2-fluoroallylboration of aromatic and aliphatic
aldehydes.
PMID- 29947416
TI - Coinheritance of biallelic SLURP1 and SLC39A4 mutations cause a severe
genodermatosis with skin peeling and hair loss all over the body.
PMID- 29947417
TI - Cinnamon and Cassia Nomenclature Confusion: A Challenge to the Applicability of
Clinical Data.
AB - Several Cinnamomum species' barks are generally labeled as cinnamon, although
only Cinnamomum verum carries the common name of true cinnamon. Cassia, a common
name for a related species, is rarely used on labels; instead, various cassia
types may also be labeled "cinnamon." Confusion of true cinnamon and cassia
spices in foods generally does not present a risk to health, except possibly at
the highest intake levels. However, clinical studies with Cinnamomum
investigational products have been published that inadequately describe or lack
botanical identification information. The results of such studies are confounded
by an inability to determine which species was responsible for the observed
effects. Due to differences in the quality and composition of various Cinnamomum
species, safety and efficacy data are not generalizable or transferable.
Pharmacopeial monographs for characterizing the identity, composition, purity,
quality, and strength of Cinnamomum investigational products should be applied to
remove the ambiguity of cinnamon.
PMID- 29947418
TI - Patients' preferences for treatment after neoadjuvant chemoradiotherapy for
oesophageal cancer.
AB - BACKGROUND: After neoadjuvant chemoradiotherapy (nCRT) plus surgery for
oesophageal cancer, 29 per cent of patients have a pathologically complete
response in the resection specimen. Active surveillance after nCRT (instead of
standard oesophagectomy) may improve health-related quality of life (HRQoL), but
patients need to undergo frequent diagnostic tests and it is unknown whether
survival is worse than that after standard oesophagectomy. Factors that influence
patients' preferences, and trade-offs that patients are willing to make in their
choice between surgery and active surveillance were investigated here. METHODS: A
prospective discrete-choice experiment was conducted. Patients with oesophageal
cancer completed questionnaires 4-6 weeks after nCRT, before surgery. Patients'
preferences were quantified using scenarios based on five aspects: 5-year overall
survival, short-term HRQoL, long-term HRQoL, the risk that oesophagectomy is
still necessary, and the frequency of clinical examinations using endoscopy and
PET-CT. Panel latent class analysis was used. RESULTS: Some 100 of 104 patients
(96.2 per cent) responded. All aspects, except the frequency of clinical
examinations, influenced patients' preferences. Five-year overall survival, the
chance that oesophagectomy is still necessary and long-term HRQoL were the most
important attributes. On average, based on calculation of the indifference point
between standard surgery and active surveillance, patients were willing to trade
off 16 per cent 5-year overall survival to reduce the risk that oesophagectomy is
necessary from 100 per cent (standard surgery) to 35 per cent (active
surveillance). CONCLUSION: Patients are willing to trade off substantial 5-year
survival to achieve a reduction in the risk that oesophagectomy is necessary.
PMID- 29947419
TI - Factors affecting periodontal disease referral and the adherence to guidelines
among general dentists.
AB - BACKGROUND: Current research highlights a need to investigate the factors
affecting periodontal disease referral. Limited literature exists on periodontal
disease referral in Australia and no comparison to the periodontal disease
referral guidelines exists. OBJECTIVE: This study analyses the factors affecting
periodontal disease referral and the adherence to guidelines in general dentists
in Queensland, Australia. METHODS: Fifty-seven general dentists who are members
of the Australian Dental Association (Queensland) undertook an online survey.
RESULTS: The disease factor regarded as most important (90% of respondents) was
unresolved inflammation upon re-evaluation. The non-disease factor regarded as
most important (79% of respondents) was the operator's level of training. There
is low awareness of the guidelines (36.7%) yet a reasonable adherence to them
(78.3%). Of those aware of the guidelines, there was a statistically significant
poorer adherence to the guidelines compared to those unaware (P = 0.036), while
there is no significant difference in the adherence to guidelines between those
who have and those who have not attended continuing professional development
(CPD) courses (P = 0.66). CONCLUSIONS: Adherence to current guidelines is not
significantly impacted by the level of awareness of the guidelines or CPD
attendance. The results from this study suggest a need to refine the current
guidelines to better inform decisions about periodontal disease referrals.
PMID- 29947420
TI - Profertility effects of Shilajit on cadmium-induced infertility in male mice.
AB - Shilajit is claimed as a Vajikarak (aphrodisiac) and used for the treatment of
male infertility by traditional healers of the Indian subcontinent. Therefore,
the present investigation was designed to assess the effectiveness of Shilajit
for treatment of male infertility resulting from exposure to perilous chemicals.
Effect of daily oral administration (p.o.) of Shilajit (50 mg, 100 mg and 200
mg/Kg BW) was investigated for a single spermatogenic cycle (35 days) in cadmium
induced (2 mg/Kg BW, p.o. for 35 days) infertile adult (12-14 week) swiss male
mice. Shilajit treatment increased weights of reproductive organs, testicular
daily sperm production, activities of testicular Delta5 3beta-HSD and 17 beta-HSD
enzymes and serum level of testosterone. Histopathological evaluation of testis
revealed that Shilajit restored spermatogenesis as reflected by a gradual
augmentation in germ cell layers with increased doses of Shilajit compared to
cadmium-treated mice. Further, Shilajit treatment reverted back the adverse
effects of cadmium on motility and concentration of spermatozoa. Secretory
activities of the epididymis and seminal vesicle and libido, fertility and the
number of litters per female were also improved by Shilajit in cadmium-treated
mice. Results thus suggest the potent androgenic nature of Shilajit and its role
in fertility improvement against cadmium-induced infertility.
PMID- 29947421
TI - Spatio-temporal variation in fitness responses to contrasting environments in
Arabidopsis thaliana.
AB - The evolutionary response of organisms to global climate change is expected to be
strongly conditioned by preexisting standing genetic variation. In addition,
natural selection imposed by global climate change on fitness-related traits can
be heterogeneous over time. We estimated selection of life-history traits of an
entire genetic lineage of the plant Arabidopsis thaliana occurring in north
western Iberian Peninsula that were transplanted over multiple years into two
environmentally contrasting field sites in southern Spain, as southern
environments are expected to move progressively northwards with climate change in
the Iberian Peninsula. The results indicated that natural selection on flowering
time prevailed over that on recruitment. Selection favored early flowering in six
of eight experiments and late flowering in the other two. Such heterogeneity of
selection for flowering time might be a powerful mechanism for maintaining
genetic diversity in the long run. We also found that north-western A. thaliana
accessions from warmer environments exhibited higher fitness and higher
phenotypic plasticity for flowering time in southern experimental facilities.
Overall, our transplant experiments suggested that north-western Iberian A.
thaliana has the means to cope with increasingly warmer environments in the
region as predicted by trends in global climate change models.
PMID- 29947422
TI - Specialized functions of resident macrophages in brain and heart.
AB - The functions of macrophages in healthy tissues extend beyond their well
established roles as immune sentinels and effectors. Among tissues, cells of the
brain and heart possess unique excitatory properties that likely demand special
support. Accordingly, existing evidence demonstrates that microglia in the brain
has an active role in synaptic organization, control of neuronal excitability,
phagocytic removal of debris, and trophic support during brain development. In
the heart, recent studies suggest that cardiac macrophages are involved in the
regulation of heart homeostasis by phagocytosis, production of trophic, and
immune-related factors, and by forming direct contacts with cardiomyocytes to
regulate electrical conduction. In this review, we discuss mechanisms associated
with the high degree of specialization of resident macrophages in both tissues,
their origin and heterogeneity, and their contributions in regulating homeostasis
under steady-state and pathological conditions.
PMID- 29947423
TI - Inhibitory effects of mycosporine-2-glycine isolated from a halotolerant
cyanobacterium on protein glycation and collagenase activity.
AB - : Mycosporine-2-glycine (M2G), isolated from the halotolerant cyanobacterium
Aphanothece halophytica, was purified and characterized in order to determine its
utility as a cosmetic and pharmaceutical ingredient. M2G efficiently inhibited
protein crosslinking. The inhibitory activity of M2G was significantly greater
than that of the well-known Maillard reaction inhibitor aminoguanidine. In
addition, M2G and other known mycosporine-like amino acids inhibited bacterial
collagenase activity. To the best of our knowledge, this is the first report
describing that M2G specifically inhibits the formation of advanced glycation end
products (AGEs), which play a critical role in ageing process and age-related
diseases. These observations indicate that M2G may have potential therapeutic
applications by suppressing the formation of AGEs and inhibiting excess
collagenase activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Mycosporine-like
amino acids (MAAs) are known as multifunctional natural compounds. The MAA
mycosporine-2-glycine (M2G), isolated from the halotolerant cyanobacterium
Aphanothece halophytica, has potential therapeutic applications for the
prevention of skin ageing. Purified M2G was endotoxin-free. M2G had greater
inhibitory activity of protein cross-linking compared with well-known inhibitor,
aminoguanidine and hindered bacterial collagenase activity. The mechanisms for
these inhibitory activities of M2G are discussed in this study.
PMID- 29947424
TI - Basal-subtype bladder tumours show a 'hot' immunophenotype.
AB - AIMS: Basal and luminal molecular subgroups of muscle-invasive urothelial
carcinoma (UC) can be recognised by the use of immunohistochemical markers.
Studies have shown that responses to chemotherapy and outcomes differ among these
subtypes. High-grade UC of the bladder is an immunogenic neoplasm that induces a
substantial intratumoral and peritumoral immune response; the phenotype of
infiltrating immune cells may yield prognostic information and predict response
to therapy. In this study, we aimed to correlate the immunohistochemical
phenotype of high-grade UC with immune microenvironment composition. METHODS AND
RESULTS: Two hundred and thirty-five cases of high-grade UC treated with
cystectomy were reviewed. Clinicopathological variables for each case were
recorded, and disease-free survival at last follow-up was calculated. Invasive
front inflammation and tumour-infiltrating lymphocytes were scored for each case.
Two hundred and seven cases were used to construct a triplicate-core tissue
microarray (TMA), with sections stained for cytokeratin (CK) 5/6 and GATA3. Of
the evaluable cases, 167 were designated as luminal (CK5/6- and GATA3+) and 29 as
basal (CK5/6+ and GATA3-). Additional sequential TMA sections were stained for
CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, programmed cell death protein 1 (PD-1),
and programmed death-ligand 1 (PD-L1) (SP263). Basal-subtype tumours showed a
trend towards worse disease-specific survival (P = 0.078). There were
statistically significant associations between basal subtype and CD8 expression
(P = 0.008), PD-1 expression (P = 0.001), and PD-L1 expression (P = 0.014). Lower
CD4/CD8 and increased CD8/FOXP3 ratios (P = 0.047 and P = 0.031, respectively)
were also identified in the basal-subtype group. CONCLUSIONS: Basal-subtype high
grade UC has an abundance of CD8+ T cells with increased expression of inhibitory
markers, indicative of a 'hot' immunophenotype.
PMID- 29947425
TI - Persistent reticulocytosis in a case of poodle macrocytosis.
AB - A healthy 14-year-old, male neutered, Miniature Poodle was found to have a
persistent erythrocyte macrocytosis and reticulocytosis with a normal and stable
HCT. The hematologic features of macrocytosis, increased Howell-Jolly bodies, and
metarubricytosis, in the absence of anemia or other cytopenias, combined with the
cytologic evidence of bone marrow erythroid dysplasia, including megaloblastosis,
binuclearity, increased mitotic activity, and nuclear fragmentation, are
consistent with previous reports of congenital dyserythropoiesis termed poodle
macrocytosis. We speculate that the additional presence of persistent
reticulocytosis in the absence of an identifiable stimulus for accelerated
erythropoiesis may represent a phenotypic variation of this inherited condition,
and the morphologic abnormalities of the dyserythropoiesis are described.
PMID- 29947428
TI - Commentary regarding: "The effect of simulated space radiation on the N
glycosylation of human immunoglobulin G1".
AB - Deep space missions, including Mars voyages, are an important area of research.
Protection of astronauts' health during these long-term missions is of paramount
importance. The paper authored by Szarka et al. entitled "The effect of simulated
space radiation on the N-glycosylation of human immunoglobulin G1" is indeed a
step forward in this effort. Despite numerous strengths, there are some
shortcomings in this paper including an incomplete description of the space
radiation environment as well as discussion of the resulting biological effects.
Due to complexity of the space radiation environment, a careful analysis is
needed to fully evaluate the spectrum of particles associated with solar particle
events and galactic cosmic radiation. The radiation source used in this
experiment does not reproduce the range of primary galactic cosmic radiation and
solar particle events particles and their associated energies. Furthermore, the
effect of radiation interactions within the spacecraft shell and the potential
effects of microgravity are not considered. Moreover, the importance of
radioadaptation in deep space missions that is confirmed in a NASA report is
neither considered. Other shortcomings are also discussed in this commentary.
Considering these shortcomings, it can be argued that Szarka et al. draw
conclusions based on an incomplete description of the space radiation environment
that could affect the applicability of this study.
PMID- 29947426
TI - Role of chemokines in ectopic lymphoid structures formation in autoimmunity and
cancer.
AB - Ectopic (or tertiary) lymphoid structures (ELS) are organized aggregates of
lymphocytes resembling secondary lymphoid organs and developing in chronically
inflamed nonlymphoid tissues during persistent infections, graft rejection,
autoimmune conditions, and cancer. In this review, we will first depict the
mechanisms regulating ELS generation, focusing on the role played by lymphoid
chemokines. We will then characterize ELS forming in target organs during
autoimmune conditions, here exemplified by rheumatoid arthritis, and cancer,
highlighting the relevance of the tissue-specific factors. Finally, we will
discuss the clinical significance of ELS and the therapeutic potential of their
inhibition and/or enhancement depending on the disease considered.
PMID- 29947429
TI - Development of a new graduate public health nurse residency program using the
core competencies of public health nursing.
AB - BACKGROUND: Due to the continued shortage of public health nurses, some local
public health agencies have begun hiring new graduate baccalaureate nurses into
the public health nurse role. These new graduates require an increased level of
support for transition to practice. AIMS: The goal of this project was creation
of a transition to practice program designed specifically to meet the needs of
new graduates hired in public health settings. METHODS: The core competencies of
public health nursing were used as a framework to develop this residency program.
A group of public health staff, supervisors, and faculty met monthly for three
years to develop this program. Key features include general orientation,
preceptors, looping experiences, case studies and peer support. RESULTS: The
program is available as a web resource beginning spring 2018. In order to
evaluate this program, data on job satisfaction, employee retention and level of
competence in the core competencies of public health will occur using instruments
administered prior to beginning and immediately following completion of the new
graduate residency. DISCUSSION: The components of the program mirror best
practices for new graduate residencies and are based on core competencies for
public health nursing. This residency program is an important step for enhancing
the professional development of new baccalaureate graduates in public health
settings, and preparing the next generation of public health nurses. CONCLUSION:
Through the increased support and intentional education of the residency program,
public health agencies will be able to attract and retain new graduates who
develop the essential knowledge and skills to provide safe and effective care in
the public health setting.
PMID- 29947427
TI - Epigenetics of T cell aging.
AB - T cells are a heterogeneous population of cells that differ in their
differentiation stages. Functional states are reflected in the epigenome that
confers stability in cellular identity and is therefore important for naive as
well as memory T cell function. In many cellular systems, changes in chromatin
structure due to alterations in histone expression, histone modifications and DNA
methylation are characteristic of the aging process and cause or at least
contribute to cellular dysfunction in senescence. Here, we review the epigenetic
changes in T cells that occur with age and discuss them in the context of
canonical epigenetic marks in aging model systems as well as recent findings of
chromatin accessibility changes in T cell differentiation. Remarkably,
transcription factor networks driving T cell differentiation account for many of
the age-associated modifications in chromatin structures suggesting that loss of
quiescence and activation of differentiation pathways are major components of T
cell aging.
PMID- 29947430
TI - On the impact of interhemispheric white matter: Age, executive functioning, and
dedifferentiation in the frontal lobes.
AB - INTRODUCTION: In middle age, declines in executive functioning (EF) are
associated with decrements in the quality and/or quantity of white and grey
matter. Recruitment of homologous regions has been identified as a compensatory
mechanism for cognitive decline in later middle age; however, research into
neural substrates of EF has yet to be guided by dedifferentiation models. We
hypothesized that frontal-parietal grey matter volume, interhemispheric white
matter, and intrahemispheric white matter fractional anisotropy will be
predictive of EF. Further, we hypothesized that the comparative association
between interhemispheric white matter and EF will increase with age, because of
compensatory recruitment. METHODS: Neurocognitive test data, DTI, and T1 MPRAGE
scans (n = 444) were obtained from the NKI-Rockland Sample. Structural equation
modeling was used to examine the relationship between age, EF, interhemispheric
white matter (forceps minor; FM), intrahemispheric white matter (superior
longitudinal fasciculus; SLF), and a frontal-parietal grey matter network. EF and
grey matter were modelled as latent variables, with EF examined as the criterion.
Additionally, a subsample of participants aged 55 to 85 (n = 168) was analyzed to
examine the influence of age related compensatory mechanisms. RESULTS: There was
a significant relationship between FM, grey matter, and EF, which was fully
mediated by age. There was a significant relationship between SLF and EF, which
was not mediated by age. For older adults, only the age-mediated pathway from FM
to EF was significant. DISCUSSION: Using structural imaging data, support was
found for age-related interhemispheric mechanisms of compensation, but not
intrahemispheric mechanisms.
PMID- 29947431
TI - Conserved aspartate-to-glycine mutation in tyrosinase is associated with albino
phenotype in domestic guinea pigs (Cavia porcellus).
PMID- 29947433
TI - Evaluation of Histogel- and Gelfoam-embedded bronchoalveolar lavage and
transtracheal wash fluids compared with cytocentrifuged and sediment smear
preparations.
AB - BACKGROUND: Storage and temperature significantly impact bronchoalveolar lavage
fluid (BALF) analysis, and shipment of samples to diagnostic laboratories is
often necessary. Alternative sample preparation methods could limit storage and
temperature effects. OBJECTIVES: This study aimed to determine if airway wash
samples that were fixed in formalin after being embedded in Histogel or Gelfoam
gave comparable results to fresh cytocentrifuged or sediment smear preparations
for the evaluation of cell morphology. METHODS: Eleven bronchoalveolar lavage and
3 transtracheal wash fluids were available, including 8 canine, 1 feline, and 5
equine samples. Cytocentrifuged and sediment smear preparations were prepared for
routine analysis. Airway fluids were reserved for further evaluation. Total
nucleated cell counts (TNCCs) were determined using a hemocytometer. The
remaining fluid was used for Histogel and Gelfoam preparations. Each preparation
was analyzed by a single board-certified clinical pathologist and assigned
cellularity (1-3) and morphology scores (1-4). RESULTS: Cellularity and
morphology were significantly worse for the sediment smear, Histogel, and Gelfoam
preparations compared with the cytocentrifuged preparations. The Gelfoam
preparations had significantly worse cellularity scores than all other methods.
Cellularity scores for sediment smears and Histogel preparations were
significantly correlated with TNCCs. CONCLUSIONS: TNCCs impacted the cellularity
of the sediment smears and Histogel preparations. Cytocentrifuged preparations
resulted in the best cellularity and morphology and are, therefore, recommended
whenever possible. Neither the Histogel nor the Gelfoam methods demonstrated any
advantage over sediment smear preparations, and both performed poorly when
compared with cytocentrifuged preparations. Therefore, we do not recommend the
use of these methods.
PMID- 29947432
TI - Phylogenetic analyses of bacteria associated with the processing of iru and ogiri
condiments.
AB - : Analysis of the bacterial community dynamics during the production of
traditional fermented condiments is important for food safety assessment, quality
control and development of starter culture technology. In this study, bacteria
isolated during the processing of iru and ogiri, two commonly consumed condiments
in Nigeria, were characterized based on phylogenetic analyses of the bacterial
16S rRNA gene. A total of 227 isolates were obtained and clustered into 12
operational taxonomic units (OTUs) based on 97% 16S rRNA gene similarity. The
OTUs spanned three phyla (Firmicutes, Actinobacteria and Proteobacteria), and
nine genera: Acinetobacter, Aerococcus, Bacillus, Enterococcus, Enterobacter,
Lysinibacillus, Micrococcus, Proteus and Staphylococcus. OTUs closely related to
species of Bacillus dominated the processing stages of both condiments. Although
no single OTU occurred throughout iru processing stages, an OTU (mostly related
to B. safensis) dominated the ogiri processing stages indicating potentials for
the development of starter culture. However, other isolates such as those of
Enterococcus spp. and Lysinibacillus spp. may be potential starters for iru
fermentation. Presumptive food-borne pathogens were also detected at some stages
of the condiments' processing, possibly due to poor hygienic practices.
SIGNIFICANCE AND IMPACT OF THE STUDY: Iru and ogiri are important condiments used
for flavour enhancement in foods and serve as protein substitutes in diets among
rural populations across West Africa. Consumption of these condiments is growing,
reinforcing the need to scale up their production. Production of these condiments
includes spontaneous fermentation, which often leads to inconsistent product
quality and unguaranteed safety. This study has demonstrated the bacterial
succession in iru and ogiri processing and highlights species that could be
selected and exploited for starter culture development. This study provides a
starting point to produce quality and microbiologically safe iru and ogiri
condiments.
PMID- 29947434
TI - Using the Scoring Hip Osteoarthritis with Magnetic Resonance Imaging (SHOMRI)
system to assess intra-articular pathology in femoroacetabular impingement.
AB - There is currently no widely accepted classification system of intra-articular
damage in the setting of femoroacetabular impingement (FAI). The goal of this
study is to correlate the Scoring Hip Osteoarthritis with Magnetic Resonance
Imaging (SHOMRI) system with arthroscopic findings in symptomatic FAI patients to
justify its use in this setting. Symptomatic FAI patients scheduled for hip
arthroscopy were prospectively enrolled. Prior to surgery, radiographs, and an
MRI were obtained of the affected hip and all patients completed the Hip
disability and Osteoarthritis Outcome Score (HOOS) questionnaire. Each MRI was
graded using the SHOMRI system. Intraoperatively, cartilage and labral injury
grades were recorded. SHOMRI scores were then correlated with the intraoperative
cartilage and labral grades as well as preoperative radiographic findings and
HOOS scores. Forty-three patients were analyzed (mean age 35.7 years, 58.1%
male). SHOMRI total scores correlated with intraoperative femoral cartilage grade
(rho = 0.42; p = 0.002), acetabular cartilage grade (rho = 0.30; p = 0.046), and
labral tear grade (rho = 0.42; p = 0.003) as well as with preoperative Tonnis
grade (rho = 0.37, p = 0.013), HOOS pain score (rho = -0.33; p = 0.039), HOOS ADL
score (rho = -0.39; p = 0.007), and HOOS sports score (rho = -0.30; p = 0.037).
In conclusion, total scores from the SHOMRI system showed significant correlation
with arthroscopic findings as well as radiographic gradings and clinical symptoms
in patients with FAI. Use of this quantitative system to assess the burden of
chondrolabral damage in FAI appears valid. (c) 2018 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res.
PMID- 29947435
TI - Advances in Native Chemical Ligation-Desulfurization: A Powerful Strategy for
Peptide and Protein Synthesis.
AB - Cysteine-based native chemical ligation (NCL) has been a very powerful approach
for convergent synthesis of peptides and proteins. However, owing to the low
abundance of cysteine (Cys) in proteins, applications of NCL in protein chemical
synthesis are limited. To expand the peptide ligation toolbox, NCL followed by
desulfurization has been developed to enable peptide ligation at Xaa-Ala
conjunctions, that is, formal "alanine ligation". In this regard, effective
peptide desulfurization methods are critical. This Concept article summarizes the
development of different desulfurization strategies for peptide and protein
chemical synthesis.
PMID- 29947436
TI - Tolerance to a haemorrhagic challenge during heat stress is improved with
inspiratory resistance breathing.
AB - NEW FINDINGS: What is the central question of this study? Does inspiratory
resistance breathing improve tolerance to simulated haemorrhage in individuals
with elevated internal temperatures? What is the main finding and its importance?
The main finding of this study is that inspiratory resistance breathing modestly
improves tolerance to a simulated progressive haemorrhagic challenge during heat
stress. These findings demonstrate a scenario in which exploitation of the
respiratory pump can ameliorate serious conditions related to systemic
hypotension. ABSTRACT: Heat exposure impairs human blood pressure control and
markedly reduces tolerance to a simulated haemorrhagic challenge. Inspiratory
resistance breathing enhances blood pressure control and improves tolerance
during simulated haemorrhage in normothermic individuals. However, it is unknown
whether similar improvements occur with this manoeuvre in heat stress conditions.
In this study, we tested the hypothesis that inspiratory resistance breathing
improves tolerance to simulated haemorrhage in individuals with elevated internal
temperatures. On two separate days, eight subjects performed a simulated
haemorrhage challenge [lower-body negative pressure (LBNP)] to presyncope after
an increase in internal temperature of 1.3 +/- 0.1 degrees C. During one trial,
subjects breathed through an inspiratory impedance device set at 0 cmH2 O of
resistance (Sham), whereas on a subsequent day the device was set at -7 cmH2 O of
resistance (ITD). Tolerance was quantified as the cumulative stress index.
Subjects were more tolerant to the LBNP challenge during the ITD protocol, as
indicated by a > 30% larger cumulative stress index (Sham, 520 +/- 306 mmHg min;
ITD, 682 +/- 324 mmHg min; P < 0.01). These data indicate that inspiratory
resistance breathing modestly improves tolerance to a simulated progressive
haemorrhagic challenge during heat stress.
PMID- 29947437
TI - Intraoperative versus postoperative rendezvous endoscopic retrograde
cholangiopancreatography to treat common bile duct stones during cholecystectomy.
AB - BACKGROUND AND AIM: The rendezvous postoperative endoscopic retrograde
cholangiopancreatography (ERCP) technique has been introduced as a modification
of the single-session rendezvous intraoperative ERCP procedure in the management
of concurrent common bile duct stones during cholecystectomy. There are no
reports on the impact of this modified technique on post-ERCP morbidity. The
objective of the present study was to study and compare the rendezvous techniques
in terms of procedure-associated morbidities, such as post-ERCP pancreatitis and
postoperative infections. METHODS: The Swedish National Registry for Gallstone
Disease and ERCP was searched for ERCP procedures cross-matched with
cholecystectomies for the same patient carried out for gallstone indications
between 2008 and 2014. A total of 1770 rendezvous ERCP procedures were retrieved
and included in this study. The ERCP procedures were considered rendezvous
intraoperative or rendezvous postoperative, depending on whether the ERCP
procedure was carried out during or after completing the cholecystectomy.
RESULTS: There were 1205 and 565 ERCP procedures in the rendezvous intraoperative
and the rendezvous postoperative groups, respectively. The cohorts were similar
in age and gender distribution. Overall complication rates were higher in the
rendezvous postoperative group compared with the rendezvous intraoperative group
(19.7% vs 14%, P = 0.004), involving specifically post-ERCP pancreatitis (6.4% vs
3.2% P = 0.003) and postoperative infections (4.4% vs 2.3% P = 0.028). Despite
similar stone clearance rates, there were higher rates of retained stones in the
rendezvous postoperative group (5.5% vs 0.6%, P < 0.001). CONCLUSIONS: Single
session rendezvous intraoperative ERCP is superior to the rendezvous
postoperative ERCP technique in terms of post-ERCP pancreatitis and postoperative
infections.
PMID- 29947438
TI - Azaacenes Bearing Five-Membered Rings.
AB - We report the synthesis of processible (dihydro)pyracyclene- and acenaphthylene
substituted azaacenes using condensation reactions in solution. The targets are
characterized via cyclic voltammetry, X-ray crystallography, UV/Vis, fluorescence
spectroscopy and DFT/NICS calculations. Formal hydrogenation of the annulated
five-membered ring surprisingly alters emission in the solid-state as a
consequence of modulation of aromaticity and HOMO-LUMO overlap. Five highly
fluorescent, crystalline azaacenes were investigated as emitters in organic light
emitting diodes, and their performance with respect to luminance and efficiency
was compared to that of structurally related azaacenes.
PMID- 29947439
TI - Endoscopic mucosal resection by double-balloon enteroscopy can be an alternative
in small bowel venous malformations.
PMID- 29947440
TI - Pancreatic cysts: Is the answer on the wall?
PMID- 29947441
TI - Venous blood provides lower glucagon-like peptide-1 concentrations than
arterialized blood in the postprandial but not the fasted state: Consequences of
sampling methods.
AB - NEW FINDINGS: What is the central question of this study? Glucagon-like peptide-1
(GLP-1) is an important obesity/diabetes target, with effects dependent on
circulating GLP-1 concentrations. Peripheral tissues extract GLP-1; therefore,
sampling venous versus arterialized blood might provide different GLP-1
concentrations. This study examined whether arterialization alters GLP-1
concentrations during fasting and feeding. What is the main finding and its
importance? This study demonstrates that venous blood provides lower postprandial
but not fasting GLP-1 concentrations versus arterialized blood. Therefore, when
accurate assessment of postprandial peripheral availability of GLP-1 is required,
blood sampling methods should be considered carefully, reported clearly, and
arterialization is recommended. ABSTRACT: Glucagon-like peptide-1 (GLP-1)
displays concentration-dependent effects on metabolism, appetite and
angiogenesis; therefore, accurate determination of circulating GLP-1
concentrations is important. In this study, we compared GLP-1 concentrations in
venous versus arterialized blood in both fasted and fed conditions. Venous and
arterialized blood samples were obtained simultaneously from 10 young, healthy
men before and 30, 60 and 120 min after ingestion of 75 g glucose. Plasma GLP-1
concentrations increased in response to glucose ingestion (time effect, P < 0.01)
and to a lesser extent in venous versus arterialized plasma (time *
arterialization interaction, P < 0.01). Accordingly, the plasma incremental area
under the curve was lower in venous versus arterialized plasma (974 +/- 88 versus
1214 +/- 115 pmol l (120 min)-1 , respectively, P = 0.049). In the postprandial
state, there was a positive relationship between arterialized GLP-1
concentrations and the venous-arterialized difference in GLP-1 concentrations (r2
= 0.51; P < 0.01). Both arterialized and venous peak GLP-1 concentrations showed
positive relationships with peak arterialized insulin concentrations (both r2 >
0.6, P < 0.01). Venous sampling results in lower concentrations of GLP-1 in the
postprandial but not the fasted state compared with arterialized blood. This
absolute difference is biologically meaningful and is magnified when GLP-1
availability is high. Therefore, sampling from arterialized blood may provide a
better chance of detecting small differences in postprandial GLP-1 availability
with interventions. If absolute GLP-1 concentrations are of interest, the blood
sampling method should be considered carefully and reported clearly.
PMID- 29947442
TI - Do HIV treatment eligibility expansions crowd out the sickest? Evidence from
rural South Africa.
AB - OBJECTIVE: The 2015 WHO recommendation to initiate all HIV patients on
antiretroviral therapy (ART) at diagnosis could potentially overextend health
systems and crowd out sicker patients, mitigating the policy's impact. We
evaluate whether South Africa's prior eligibility expansion from CD4 <= 200 to
CD4 <= 350 cells/MUl reduced ART uptake in the sickest patients. METHODS: Using
data on all patients presenting to the Hlabisa HIV Treatment and Care Programme
in KwaZulu-Natal from April 2010 to June 2012 (n = 13 809), we assessed the
impact of the August 2011 eligibility expansion on the number of patients seeking
care, number initiating ART and time from HIV diagnosis to ART initiation among
patients always eligible (CD4 0-200), newly eligible (CD4 201-350) and not yet
eligible by CD4 count (>350). We used interrupted time series methods to control
for long-run trends and isolate the effect of the policy. RESULTS: Expanding ART
eligibility led to an increased number of patients initiating ART per month
[+95.5; 95% CI (-1.3; 192.3)]. Newly eligible patients (CD4 201-350) initiated
treatment 47% faster than before (95% CI 19%; 82%), while the sickest patients
(CD4 <= 200) saw no decline in the monthly number of patients initiating
treatment or the rate of treatment uptake. CONCLUSION: The Hlabisa programme
successfully extended ART to patients with CD4 <= 350 cells/MUl, while ensuring
that the sickest patients did not experience delays in ART initiation. Treatment
programmes must be vigilant to maintain quality of care for the sickest as
countries move to treat all patients irrespective of CD4 count.
PMID- 29947443
TI - Beyond the bucket list: Unfinished and business among advanced cancer patients.
AB - OBJECTIVE: The study aims to examine the prevalence and common themes of
unfinished business (UB) and its associations with distress among advanced cancer
patients. METHODS: A total of 223 patients from a larger randomized controlled
trial of Individual Meaning-Centered Psychotherapy (IMCP) completed self-report
questionnaires that assessed UB and UB-related distress, hopelessness, desire for
hastened death, anxiety and depression, quality of life, spiritual well-being,
and purpose/meaning. Unfinished business themes were identified by qualitative
analysis of open-ended data. RESULTS: A total of 161 (72%) patients reported the
presence of UB. The mean UB-related distress score was 7.01 (SD = 2.1) out of 10.
Results of independent t tests showed that patients with UB reported
significantly higher levels of anxiety and lower levels of existential
transcendence than patients without UB. Linear regression equations indicated
that UB-related distress significantly predicted hopelessness (F1,154 = 9.54, P
< 0.05, R2 = 0.058), anxiety (F1,154 = 4.31, P < 0.05, R2 = 0.027), personal
meaning (F1,136 = 6.18, P < 0.05, R2 = 0.043), and existential transcendence
(F1,119 = 6.7, P < 0.05, R2 = 0.053). Ten UB themes emerged from open-ended
responses; UB themes were not associated with UB-related distress or
psychological adjustment. CONCLUSIONS: Unfinished business was both prevalent and
distressing in our sample. Findings underscore the need to develop and implement
interventions designed to help patients resolve or find solace with UB.
PMID- 29947444
TI - Effectiveness of Active Support for adults with intellectual disability in
residential settings: Systematic review and meta-analysis.
AB - BACKGROUND: The review examined the effectiveness of Active Support (RQ1) and
stakeholders' experiences of the model (RQ2). METHOD: Data were meta-analysed
(RQ1; studies = 14) and synthesized narratively (RQ2; studies = 10). RESULTS: By
follow-up (6 months post-training), effect sizes (RQ1) for resident total
activity engagement were significant and ranged from small (d = 0.33, 95% CIs:
0.10-0.50) to large (Tau-U = 0.95, 95% CIs: 0.64-1.25) depending on study design.
Follow-up changes in staff assistance were moderate (d = 0.56, 95% CIs: 0.23
0.89; Tau-U 0.63, 95% CIs: 0.32-0.93) and large for quality of support (d = 1.03,
95% CIs: 0.61-1.44). Other outcomes did not change. CONCLUSIONS: Active Support
was more effective following complete staff training, in larger settings, at
lower staff-to-resident ratios and with less experienced staff. Active Support
training and outcomes were valued by staff and residents (RQ2), and staff
experienced increased job satisfaction. Lower staff turnover and organizational
readiness appear crucial for maintaining implementation.
PMID- 29947445
TI - Modelled biophysical impacts of conservation agriculture on local climates.
AB - Including the parameterization of land management practices into Earth System
Models has been shown to influence the simulation of regional climates,
particularly for temperature extremes. However, recent model development has
focused on implementing irrigation where other land management practices such as
conservation agriculture (CA) has been limited due to the lack of global
spatially explicit datasets describing where this form of management is
practiced. Here, we implement a representation of CA into the Community Earth
System Model and show that the quality of simulated surface energy fluxes
improves when including more information on how agricultural land is managed. We
also compare the climate response at the subgrid scale where CA is applied. We
find that CA generally contributes to local cooling (~1 degrees C) of hot
temperature extremes in mid-latitude regions where it is practiced, while over
tropical locations CA contributes to local warming (~1 degrees C) due to changes
in evapotranspiration dominating the effects of enhanced surface albedo. In
particular, changes in the partitioning of evapotranspiration between soil
evaporation and transpiration are critical for the sign of the temperature
change: a cooling occurs only when the soil moisture retention and associated
enhanced transpiration is sufficient to offset the warming from reduced soil
evaporation. Finally, we examine the climate change mitigation potential of CA by
comparing a simulation with present-day CA extent to a simulation where CA is
expanded to all suitable crop areas. Here, our results indicate that while the
local temperature response to CA is considerable cooling (>2 degrees C), the grid
scale changes in climate are counteractive due to negative atmospheric feedbacks.
Overall, our results underline that CA has a nonnegligible impact on the local
climate and that it should therefore be considered in future climate projections.
PMID- 29947447
TI - Scurvy: A rare cause for limp in a child with autism spectrum disorder.
PMID- 29947446
TI - Predictive value of unshielded magnetocardiographic mapping to differentiate
atrial fibrillation patients from healthy subjects.
AB - BACKGROUND: P-wave duration, its dispersion and signal-averaged ECG, are
currently used markers of vulnerability to atrial fibrillation (AF). However,
since tangential atrial currents are better detectable at the body surface as
magnetic than electric signals, we investigated the accuracy of
magnetocardiographic mapping (MCG), recorded in unshielded clinical environments,
as predictor of AF occurrence. METHODS: MCG recordings, in sinus rhythm (SR), of
71 AF patients and 75 controls were retrospectively analyzed. Beside electric and
magnetic P-wave and PR interval duration, two MCG P-wave subintervals, defined P
dep and P-rep, were measured, basing on the point of inversion of atrial magnetic
field (MF). Eight parameters were calculated from inverse solution with
"Effective Magnetic Dipole (EMD) model" and 5 from "MF Extrema" analysis.
Discriminant analysis (DA) was used to assess MCG predictive accuracy to
differentiate AF patients from controls. RESULTS: All but one (P-rep) intervals
were significantly longer in AF patients. At univariate analysis, three EMD
parameters differed significantly: in AF patients, the dipole-angle-elevation
angular speed was lower during P-dep (p < 0.05) and higher during P-rep (p <
0.001) intervals. The space-trajectory during P-rep and the angle-dynamics during
P-dep were higher (p < 0.05), whereas ratio-dynamics P-dep was lower (p < 0.01),
in AF. At DA, with a combination of MCG and clinical parameters, 81.5% accuracy
in differentiating AF patients from controls was achieved. At Cox-regression, the
angle-dynamics P-dep was an independent predictor of AF recurrences (p = 0.037).
CONCLUSIONS: Quantitative analysis of atrial MF dynamics in SR and the solution
of the inverse problem provide new sensitive markers of vulnerability to AF.
PMID- 29947448
TI - First detection of Leishmania donovani in sand flies from Cameroon and its
epidemiological implications.
AB - OBJECTIVES: A sound knowledge of the vector-host-parasite transmission dynamics
is a prerequisite for adequate control measures of vector-borne diseases. To
achieve this, an entomological investigation was conducted in the cutaneous
leishmaniasis (CL) endemic focus of Mokolo District, northern Cameroon to
identify the insect vector(s) of the disease. METHODS: Phlebotomine sand flies
were collected in and around Mokolo using New Standard CDC Miniature Light Traps.
Individual sand flies were used for morphological species identification, and the
remainder of the body for DNA analysis. Sand flies were demonstrated to harbour
Leishmania spp. parasites using ITS1 PCR. Mitochondrial vertebrate-specific
Cytochrome b -PCR was used to identify blood meals ingested by female sand flies.
PCR amplicons were sequenced for Leishmania and blood sources discrimination.
RESULTS: This study revealed the presence of Leishmania donovani complex DNA (n =
1) in Phlebotomus duboscqi and of lizard-borne Leishmania tarentolae-like DNA (n
= 3) in Sergentomyia spp. in 79 sand fly specimens from Mokolo district.
CONCLUSIONS: The causative agent of CL could not be detected in potential
vectors. Instead, we found evidence for visceral leishmaniasis (VL) parasites in
Phlebotomus duboscqi as well as enzootic reptile parasites in the Mokolo area. We
recommend that an epidemiological survey be carried out in the area to evaluate
the prevalence and eventually describe the clinical manifestations of VL in the
human population. Political instability in neighbouring countries and the
resulting refugee migration are likely explanations for the emergence of VL in
Mokolo.
PMID- 29947450
TI - Adolescents' Civic Engagement: Concordant and Longitudinal Associations Among
Civic Beliefs and Civic Involvement.
AB - Associations between adolescent civic and organized activities (volunteering,
standard political, social movement, school/community, religious) and civic
beliefs (comprised of should, obligation, and respect judgments) were examined.
Cross-sectional models (N = 703, Mage = 15.87) indicated domain specificity
between adolescent civic beliefs and behaviors. Longitudinal models (n = 219,
Mage = 15.39) indicated that adolescents' standard political beliefs predicted
greater levels of standard political involvement one year later, and
school/community activities predicted greater standard political beliefs a year
later. Youth volunteering predicted lower standard political beliefs, and
standard political involvement predicted lower community service beliefs one year
later. Findings support the assessment of adolescent sociomoral civic beliefs and
demonstrate how civic experiences and civic beliefs can mutually promote each
other during adolescence.
PMID- 29947449
TI - Neutrophil-to-lymphocyte ratio to predict gastrointestinal bleeding in Henoch:
Schonlein purpura.
AB - BACKGROUND: Henoch-Schonlein purpura (HSP) is a common form of vasculitis in
children. It typically involves small vessels of the skin, the gastrointestinal
(GI) tract, joints, and kidneys. GI involvement is the most severe short-term
complication and GI bleeding is a major complication of HSP, but there is no
established predictive marker of GI bleeding. Blood neutrophil-to-lymphocyte
ratio (NLR) has been proposed as a potentially useful marker of clinical outcome
in diseases with an inflammatory component. The aim of this study was to clarify
the association of NLR with HSP and investigate the usefulness of NLR as a marker
to predict GI bleeding in children with HSP. METHODS: All patients with newly
diagnosed HSP were reviewed retrospectively. White blood cell count, hemoglobin,
platelet counts, mean platelet volume, neutrophil and lymphocyte count were
evaluated. NLR and platelet-to-lymphocyte ratio (PLR) were calculated using
complete blood count data. RESULTS: This study involved 141 HSP patients. GI
involvement was found in 65 patients (46.1%), and, of these, 15 (10.6%) had GI
bleeding. At the time of diagnosis, NLR was significantly higher (P = 0.001) and
PLR significantly lower (P = 0.032) in patients with GI bleeding than in those
without GI bleeding. On logistic regression analysis, NLR was the only
independent predictor of GI bleeding (P = 0.004). The optimal cut-off of NLR for
predicting GI bleeding was 2.86 (sensitivity, 73%; specificity, 68%).
CONCLUSIONS: NLR, a simple and easily obtainable parameter, is a potential
predictive marker of GI bleeding in children with HSP.
PMID- 29947451
TI - Safety of the Combination of PERC and YEARS Rules in Patients With Low Clinical
Probability of Pulmonary Embolism: A Retrospective Analysis of Two Large European
Cohorts.
AB - BACKGROUND: This study aimed to determine the failure rate of a combination of
the PERC and the YEARS rules for the diagnosis of pulmonary embolism (PE) in the
emergency department (ED). METHODS: We performed a retrospective analysis of two
European cohorts of emergency patients with low gestalt clinical probability of
PE (PROPER and PERCEPIC). All patients we included were managed using a
conventional strategy (D-dimer test, followed, if positive, by computed
tomographic pulmonary angiogram (CTPA). We tested a diagnostic strategy that
combined PERC and YEARS to rule out PE. The primary endpoint was a thromboembolic
event diagnosed in the ED or at 3-months follow-up. Secondary endpoints included
a thromboembolic event at baseline in the ED and a CTPA in the ED. Ninety-five
percent confidence intervals (CIs) of proportions were calculated with the use of
Wilson's continuity correction. RESULTS: We analyzed 1,951 patients (mean +/- SD
age = 47 +/- 18 years, 56% women) with an overall proportion of patients with PE
of 3.5%. Both PERC and YEARS strategies were associated with 11 missed PE in the
ED: failure rate 0.57 (95% CI = 0.32-1.02). At 3-month follow-up, the overall
failure rate was 0.83% (95% CI = 0.51-1.35). Among the 503 patients who underwent
a CTPA (26%), the use of the PERC-YEARS combination would have ruled out PE
without CTPA in 249 patients (50% [95%CI = 45%-54%], absolute reduction 13% (95%
CI = 11%-14%]). CONCLUSION: The combination of PERC then YEARS was associated
with a low risk of PE diagnostic failure and would have resulted in a relative
reduction of almost half of CTPA.
PMID- 29947452
TI - Increased use of third-generation cephalosporin antibiotics in the outpatient
setting in Korean children and adolescents.
AB - BACKGROUND: Antimicrobial resistance is a concern to public health, and
controlling antibiotic use is therefore important. This study analyzed the trend
in outpatient antibiotic prescriptions in children and adolescents in Korea.
METHODS: Using National Prescribing Sample data from the Korea Health Insurance
Review and Assessment Service between 1 January 2010 and 31 December 2014, we
analyzed outpatient systemic antibiotic (anatomical therapeutic chemical [ATC]
J01) prescriptions in patients aged 2-17 years. The antibiotic rate was defined
as the proportion of all outpatient prescriptions for antibiotics. We calculated
absolute and relative differences with 95%CI between 2010 and 2014 in the
antibiotic rate by age group (2-6, 7-11, and 12-17 years) and the percentage of
antibiotic prescriptions by antibiotic class. Seven of the most commonly used
antibiotic drugs were identified based on defined daily dose. RESULTS: A total of
7 261 176 prescriptions were written for 1 039 756 pediatric patients between
2010 and 2014. The antibiotic rate in all patients increased from 34.8% in 2010
to 70.4% in 2014, resulting in the relative difference of 102.1% (95%CI: 101.7
102.5). Extended spectrum penicillins were the most commonly prescribed
antibiotic class, accounting for 40.0-41.0% of all antibiotic prescriptions. The
use of third-generation cephalosporins increased steeply with the relative
difference of 55.7% (95%CI: 55.2-56.2). Amoxicillin/clavulanate, an extended
spectrum antibiotic drug, was the predominately used antibiotic drug but the use
of cefpodoxime, a third-generation cephalosporin, increased by 96%. CONCLUSIONS:
The use of outpatient antibiotics, especially third-generation cephalosporins,
has increased in children and adolescents in Korea.
PMID- 29947453
TI - Providers' Perceptions of Caring for Pediatric Patients in Community Hospital
Emergency Departments: A Mixed-methods Analysis.
AB - BACKGROUND: Approximately 90% of pediatric emergency care is provided in
community emergency departments (CEDs) that care for both adults and children.
Paradoxically, the majority of pediatric emergency medicine knowledge generation,
quality improvement work, and clinical training occurs in children's hospitals.
There is a paucity of information of perceptions on pediatric care from CED
providers. This information is needed to guide the development of strategies to
improve CED pediatric readiness. OBJECTIVE: The objective was to explore
interprofessional CED providers' perceptions of caring for pediatric patients.
METHODS: A preparticipation survey collected data on demographics, experience,
and comfort in caring for children. Emergency pediatric simulations were then
utilized to prime interprofessional teams for debriefings. These discussions
underwent qualitative analysis by three blinded authors who coded transcripts
into themes through an inductive method derived from grounded theory. The other
authors participated in confirmability and dependability checks. RESULTS: A total
of 171 community hospital providers from six CEDs completed surveys (49% nurses,
22% physicians, 23% technicians). The majority were PALS trained (70%) and
experienced fewer than five pediatric resuscitations in their careers (61%). Most
self-reported comfort in caring for acutely ill and injured children. From the
debriefings, three major challenge themes emerged: 1) knowledge and skill
limitations attributed to infrequency of training and actual clinical events, 2)
the emotional toll of caring for a sick child, and 3) acknowledgment of pediatric
specific quality and safety deficits. Subthemes focused on causes and potential
mitigating factors contributing to these challenges. A solution theme highlighted
novel partnering opportunities with local children's hospitals. CONCLUSION:
Interprofessional CED providers perceive that caring for pediatric patients is
challenging due to case infrequency, the emotional toll of caring for sick
children, and pediatric quality and safety deficits in their systems. These areas
of focus can be used to generate specific strategies for improving CED pediatric
readiness.
PMID- 29947454
TI - Awareness of cardiopulmonary resuscitation among parents of 3-year-old children.
AB - BACKGROUND: Out-of-hospital cardiac arrest (OHCA) in infants or toddlers mainly
occurs at home. Therefore, parents should be able to perform immediate
cardiopulmonary resuscitation (CPR) when they witness OHCA. The status of
knowledge regarding CPR among parents, however, remains unclear. The aim of the
present study was therefore to determine the factors associated with awareness of
CPR in parents of 3-year-old children. METHODS: We analyzed a subset of data from
a population-based, cross-sectional survey that served as an evaluation of a
national campaign for maternal and child health in Japan. The questionnaire was
distributed to 32 897 parents who visited public health centers for medical check
ups for their children in 2013. Multivariate logistic regression analysis was
carried out using the obtained demographic data. RESULTS: Overall, 26 971 parents
(82.0%) responded to the questionnaire. On multivariate logistic regression
analysis, birth order of the child, age of the mother at delivery, awareness of
medical facilities for emergency services at night or during the weekend, current
occupation status of the mother, and current economic status were independently
associated with CPR awareness. When the mother was employed but the parents felt
economically insufficient, the probability of having CPR knowledge decreased by
19%. Regardless of the parents' economic stability, the probability of having CPR
knowledge declined by >35% when the mother was unemployed. CONCLUSIONS: The
current occupation status of mothers and the current parent economic status
should be considered when planning educational strategies regarding CPR training
for parents.
PMID- 29947455
TI - Job satisfaction among disabled people in the sheltered workshop: Differential
analysis.
AB - This paper analyses job satisfaction and differences in factors affecting it
among workers with an intellectual disability and mental illness (MI) depending
on their work regime [special employment regime (SER) or occupational service
(OS)]. To do so, answers were analysed from 874 participants on a Job
Satisfaction Scale used in sheltered workshops in Spain. The results indicate
that job satisfaction among workers with intellectual disability and MI in both
the SER and the OS regimes is high, with the highest job satisfaction deriving
from the Items of communicating problems to resolve them. The lowest levels of
job satisfaction are related to the opportunity to take decisions and participate
at work. In the majority of the Items analysed, no differences were found on the
basis of the age groups considered nor the gender of the participants.
PMID- 29947456
TI - An exploration of communication within active support for adults with high and
low support needs.
AB - BACKGROUND: The aim was to explore the relationship between quality of active
support and communication support for people in group homes with high and low
support needs. METHODS: Data from 182 service users, 20-81 years (mean = 40), 89
with high support needs, were observed to have either good (n = 142) or poor (n =
40) communication support. Measures were of quality of active support, engagement
and staff contact; field notes provided examples of good and poor communication
supports. RESULTS: We found a relationship between the quality of communication
support and active support. Receiving good communication was associated with
higher levels of engagement. Field notes included some examples of appropriate
communication supports, but limited use of augmentative and alternative
communication (AAC). CONCLUSIONS: Staff show limited use of appropriate
communication with people having high support needs who require AAC. Strategies
to improve quality of practice are discussed.
PMID- 29947457
TI - "I don't want to take any risks even if it's gonna mean this service-user is
gonna be happier": A thematic analysis of community support staff perspectives on
delivering Transforming Care.
AB - BACKGROUND: Transforming Care is making mixed progress in supporting people with
intellectual and developmental disabilities, and complex needs, move to more
appropriate specialist accommodations closer to home. Community support staff
often spend greatest amounts of time with service-users, yet are some of the
least heard voices about why placements succeed and fail to varying extents.
METHOD: Managers and support staff (n = 13), working in ostensibly "specialist"
community placements, were interviewed about perceived barriers and facilitators
to implementing Transforming Care. Transcripts were subjected to thematic
analysis. RESULTS: Participants identified difficulties balancing people's
rights, safety and quality of life needs, and felt the system's expectations of
them are hard to deliver within the resources, legislation, values and support
models provided them. Multidisciplinary expertise was highly valued for both
emotional and practical support, but was least valued when perceived as overly
blaming or inspectorial. Specialist health input was seen to withdraw prematurely
for this particular client group. CONCLUSION: Recommendations are provided for
how staff perspectives should inform Transforming Care in interests of service
users.
PMID- 29947458
TI - Psychological status and coping styles of caregivers of individuals with
intellectual disability and psychiatric illness.
AB - BACKGROUND: The psychological status of caregivers of individuals with
intellectual disability and psychiatric illness (PI) is important for effective
management. The aim of this study was to examine the psychological status and its
relationship with coping styles among these caregivers. MATERIALS & METHODS:
Caregivers (N = 80) of individuals with intellectual disability (n = 40) and PI
(n = 40) were administered a socio-demographic questionnaire, depression, anxiety
and stress scale and COPE Inventory. RESULTS: Caregivers experienced depression,
anxiety and stress symptoms. These symptoms were found to be significantly higher
among caregivers of individuals with intellectual disability than those with PI.
The most common coping style used was religious coping. Use of positive
reinterpretation and growth was associated with lower levels of depression and
stress symptoms. CONCLUSION: Caregivers' mental health plays an important role in
the quality of care delivery and outcome. Use of appropriate coping styles can
reduce the impact of these symptoms.
PMID- 29947459
TI - "Having friends is like having marshmallows": Perspectives of transition-aged
youths with intellectual and developmental disabilities on friendship.
AB - BACKGROUND: The literature emphasizes that friendships are essential to youths'
successful transition to and adjustment in adulthood. Few studies have explored
the friendships of transition-aged youths with intellectual and developmental
disabilities (IDD), and even fewer include youths' own perspectives. This
qualitative study explored the perspectives of transition-aged youths with IDD
regarding their own experiences of friendship. METHOD: A subset of video-recorded
data of 21 interviews with seven participants (20-24 years) was extracted from a
larger study for secondary analysis. Data were analysed using thematic analysis,
informed by constructivist grounded theory methods. RESULTS: Three themes were
revealed: meanings of friends and friendship, deepening self-knowledge and
negotiating in(ter)dependence. CONCLUSIONS: The findings expand existing
knowledge about friendships of transition-aged youths with IDD. Findings can
potentially inform development of new services or enhancement of existing
services aimed at facilitating transition to adulthood for youths with IDD and
point to key areas for future research.
PMID- 29947460
TI - Health indicators in intellectual developmental disorders: The key findings of
the POMONA-ESP project.
AB - BACKGROUND: The aim of this paper was to summarize the main results of the POMONA
ESP project, the first study to explore health status in a large representative,
randomized and stratified sample of people with intellectual developmental
disorders in Spain. METHODS: The POMONA-ESP project collected information about
the health of 953 individuals with intellectual developmental disorders. RESULTS:
Diseases such as urinary incontinence, oral problems, epilepsy, constipation or
obesity were highly prevalent among the participants; with gender-differentiated
prevalences for certain conditions, and age and intellectual disability level as
risk factors for disease. Overmedication was common in the sample, and drugs were
often prescribed without any clinical indication or follow-up. The present
authors also found a lack of important relevant information about the
participant's health and a lack of adequate genetic counselling. CONCLUSIONS: Our
findings may contribute to a better understanding of health status and needs of
people with intellectual developmental disorders and suggest several courses of
action to improve their health care.
PMID- 29947461
TI - How best to support individuals with IDD as they become frail: Development of a
consensus statement.
AB - BACKGROUND: While higher rates and earlier onset of frailty have been reported
among adults with intellectual and developmental disabilities (IDD), research on
how best to support these individuals is lacking. METHOD: An international
consultation relied on three consensus building methods: the Nominal Group
Technique, an NIH consensus conference approach, and a Delphi survey. RESULTS:
There is agreement that person-centered planning and aging in place should be
guiding principles. Frailty must be considered earlier than in the general
population with the recognition that improvement and maintenance are viable
goals. Intersectoral collaboration is needed to coordinate assessments and
actions. Safety and planning for the future are important planning
considerations, as are the needs of caregivers. Ongoing research is needed.
CONCLUSION: The statement offers guidance to respond to frailty among adults with
IDD and fosters ongoing exchange internationally on best practice. As new
evidence emerges, the statement should be revisited and revised.
PMID- 29947462
TI - Beliefs about intellectual disability among employees at a state facility and
undergraduate students: An exploratory analysis.
AB - BACKGROUND: Individuals with intellectual disability are subject to
stigmatization, even among those providing services to them. METHOD: Employees
from an intermediate care facility (n = 97) and undergraduate students (n = 92)
completed measures on their attitudes, beliefs of etiological causes and
endorsement of helpful treatments and supports. RESULTS: Overall, participants
reported few stigmatizing attitudes and high levels of support for interventions.
Differences between employees and students emerged in regard to attitudes and
causal beliefs, with employees reporting more support for sheltering and less
endorsement of biomedical causes. Among students, those that reported knowing
someone with intellectual disability reported less agreement with causal factors
as well as differences in what supports were thought to be necessary or
beneficial. CONCLUSIONS: Attitudes and beliefs are interrelated and while
familiarity impacts these views, it does not necessarily lead to greater
understanding or endorsement of treatments or supports. The effects of
familiarity on attitudes and beliefs should continue to be explored.
PMID- 29947463
TI - Influence of isopropylmalate synthase OsIPMS1 on seed vigour associated with
amino acid and energy metabolism in rice.
AB - Seed vigour is an imperative trait for the direct seeding of rice.
Isopropylmalate synthase (IPMS) catalyses the committed step of leucine (Leu)
biosynthesis, but its effect on seed vigour remains unclear. In this study, rice
OsIPMS1 and OsIPMS2 was cloned, and the roles of OsIPMS1 in seed vigour were
mainly investigated. OsIPMS1 and OsIPMS2 catalyse Leu biosynthesis, and Leu
feedback inhibits their IPMS activities. Disruption of OsIPMS1 resulted in low
seed vigour under various conditions, which might be tightly associated with the
reduction of amino acids in germinating seeds. Eleven amino acids that associated
with stress tolerance, GA biosynthesis and tricarboxylic acid (TCA) cycle were
significantly reduced in osipms1 mutants compared with those in wide type (WT)
during seed germination. Transcriptome analysis indicated that a total of 1209
differentially expressed genes (DEGs) were altered in osipms1a mutant compared
with WT at the early germination stage, wherein most of the genes were involved
in glycolysis/gluconeogenesis, protein processing, pyruvate, carbon, fructose and
mannose metabolism. Further analysis confirmed that the regulation of OsIPMS1 in
seed vigour involved in starch hydrolysis, glycolytic activity and energy levels
in germinating seeds. The effects of seed priming were tightly associated with
the mRNA levels of OsIPMS1 in priming seeds. The OsIPMS1 might be used as a
biomarker to determine the best stop time-point of seed priming in rice. This
study provides novel insights into the function of OsIPMS1 on seed vigour and
should have practical applications in seed priming of rice.
PMID- 29947464
TI - Risk factors for falls in terms of attention during gait in community-dwelling
older adults.
AB - AIM: We examined factors related to conditions of life function and falls,
including eye movements and gait variability, in community-dwelling older adults
in Japan. METHODS: Participants were 82 older adults (21 men, 61 women, mean age
76.1 years). We measured eye movements and gait variability during walking, and
cognitive, attentional and life function. We compared two groups according to
their fall history, and used a multiple logistic regression analysis to determine
its relevance. RESULTS: Fixation time, which was estimated from eye movements
during obstacle crossing, and gait variability (vertical) were significantly
associated with falls. There was also a significant correlation between fixation
time and gait variability during obstacle crossing. In other words, the higher
the gait variability in older adults, the higher the risk of falls, which was due
to reduced attention estimated from eye movements during obstacle crossing that
required obstacle avoidance. CONCLUSIONS: These results show that poor attention
during gait is a critical risk factor for falls in community-dwelling older
adults. For fall prevention, it is necessary to promote exercises for attention,
and to maintain an older adult-friendly pedestrian environment. Geriatr Gerontol
Int 2018; 18: 1267-1271.
PMID- 29947465
TI - Traditional neonatal care practices in Jordan: A qualitative study.
AB - Traditional practices during the first months of neonatal life are common in
developing countries, such as Jordan. Many international studies and reports have
highlighted the fact that traditional neonatal practices are the cause of high
neonatal mortality and morbidity rates in some countries. The aim of the present
study was to identify neonatal care practices in Jordan. A descriptive,
qualitative research design was used across four Jordanian cities across diverse
regions. Forty mothers of neonates were interviewed over a period of 6 months
(from January to June 2016). Thematic and content analysis was undertaken
following Braun and Clarke's six step analysis. The results indicated that in
Jordan, home-based neonatal care comprises non-biomedical practices. Rubbing the
neonate's skin with salt, swaddling, prelacteal feeding, and other treatment
modalities are common. Further studies are necessary to determine and report on
the pros and cons of these practices in regard to neonatal health.
PMID- 29947466
TI - Genetic architecture underlying the lignin biosynthesis pathway involves
noncoding RNAs and transcription factors for growth and wood properties in
Populus.
AB - Lignin provides structural support in perennial woody plants and is a complex
phenolic polymer derived from phenylpropanoid pathway. Lignin biosynthesis is
regulated by coordinated networks involving transcription factors (TFs),
microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). However, the genetic
networks underlying the lignin biosynthesis pathway for tree growth and wood
properties remain unknown. Here, we used association genetics (additive, dominant
and epistasis) and expression quantitative trait nucleotide (eQTN) mapping to
decipher the genetic networks for tree growth and wood properties in 435
unrelated individuals of Populus tomentosa. We detected 124 significant
associations (P <= 6.89E-05) for 10 growth and wood property traits using 30 265
single nucleotide polymorphisms from 203 lignin biosynthetic genes, 81 TF genes,
36 miRNA genes and 71 lncRNA loci, implying their common roles in wood formation.
Epistasis analysis uncovered 745 significant pairwise interactions, which helped
to construct proposed genetic networks of lignin biosynthesis pathway and found
that these regulators might affect phenotypes by linking two lignin biosynthetic
genes. eQTNs were used to interpret how causal genes contributed to phenotypes.
Lastly, we investigated the possible functions of the genes encoding 4-coumarate:
CoA ligase and cinnamate-4-hydroxylase in wood traits using epistasis, eQTN
mapping and enzymatic activity assays. Our study provides new insights into the
lignin biosynthesis pathway in poplar and enables the novel genetic factors as
biomarkers for facilitating genetic improvement of trees.
PMID- 29947468
TI - A Split-Intein-Based Method for the Efficient Production of Circularized
Nanodiscs for Structural Studies of Membrane Proteins.
AB - Phospholipid nanodiscs are a native-like membrane mimetic that is suitable for
structural studies of membrane proteins. Although nanodiscs of different sizes
exist for various structural applications, their thermal and long-term stability
can vary considerably. Covalently circularized nanodiscs are a perfect tool to
overcome these limitations. Existing methods for the production of circularized
nanodiscs can be time-consuming and technically demanding. Therefore, an easy in
vivo approach, in which circularized membrane scaffold proteins (MSPs) can be
directly obtained from Escherichia coli culture, is reported herein. Nostoc
punctiforme DnaE split-intein fusions with MSPs of various lengths are used and
consistently provide circularized nanodiscs in high yields. With this approach, a
large variety of circularized nanodiscs, ranging from 7 to 26 nm in diameter,
that are suitable for NMR spectroscopy and electron microscopy (EM) applications
can be prepared. These nanodiscs are superior to those of the corresponding
linear versions in terms of stability and size homogeneity, which affects the
quality of NMR spectroscopy data and EM experiments. Due to their long-term
stability and homogeneity, the presented small circular nanodiscs are suited for
high-resolution NMR spectroscopy studies, as demonstrated with two membrane
proteins of 17 or 32 kDa in size. The presented method will provide easy access
to circularized nanodiscs for structural studies of membrane proteins and for
applications in which a defined and stable nanodisc size is required.
PMID- 29947469
TI - Honeycomb-Patterned Polyimide Film as a Versatile Coating for High-Performance
Dielectric Material.
AB - A honeycomb-patterned porous film was conveniently prepared by means of the
microemulsion method and then used as an effective coating for improving the
dielectric properties and water resistance of polyimide (PI) film while
maintaining its mechanical properties. The dielectric properties could be
regulated by tuning the structure of the porous film through controlling its
formation conditions. When suitable conditions were used, the prepared composite
PI film exhibited a significant reduction of 28.3 % in its dielectric constant
and 9.48-54.99 % in dielectric loss accompanied by an extremely low water uptake
of 0.62 % relative to the 2.47 % of flat PI film. The composite PI film also
displayed excellent durability under moist conditions, as the dielectric constant
was still below 2.4 after exposure to 75 % relative humidity for more than 12 h.
This provides a novel method to improve and control the dielectric properties of
materials. It also suggests that this film is a suitable candidate for coating
dielectric materials in high-humidity environments.
PMID- 29947467
TI - Prognostic factors of survival in HIV/HCV co-infected patients with
hepatocellular carcinoma: The CARCINOVIC Cohort.
AB - BACKGROUND & AIMS: HIV/HCV co-infected patients with hepatocellular carcinoma
(HCC) have poorer survival than HCV mono-infected patients. We aimed to evaluate
the prognostic factors for survival. METHODS: From 2006 to 2013, 55 incident HCCs
among HIV+/HCV+ patients, from three ANRS cohorts, were compared with 181 HCCs in
HIV-/HCV+ patients from the ANRS Cirvir cohort. RESULTS: HIV+/HCV+ patients were
younger (50 years [IQR: 47-53] vs 62 [54-70], P < 0.001), male (89% vs 63%, P <
0.001) than HIV-/HCV+ patients. At HCC diagnosis, both groups had a majority of
non-responders to anti-HCV-therapy, and HIV+/HCV+ patients had more frequently
known a previous cirrhosis decompensation (31% vs 14%, P = 0.005). At diagnostic
imaging, there were more infiltrative forms of HCC in HIV+/HCV+ group (24% vs
14%, P < 0.001), associated with tumour portal thrombosis in 29%. During a median
follow-up period of 11.96 [5.51-27] months since HCC diagnosis, a majority of
palliative treatments were decided in HIV+/HCV+ patients (51% vs 19%, P < 0.001).
The 1 and 2-year crude survival rates were 61% versus 78% and 47% versus 63%, P =
0.003 respectively. In a Cox model multivariate analysis adjusted for the cohort,
age and sex, the most important prognostic factor for survival was the
infiltrative form of the tumour (aRR: 8.10 [4.17-15.75], P < 0.001). CONCLUSIONS:
The radiological aggressiveness of the tumour is the best prognostic factor
associated with poorer survival of HCC in HIV+/HCV+ patients. High alpha
foetoprotein level and decompensated cirrhosis are other ones. This justifies a
particular attention to the detection and the management of small nodules in this
high-risk population.
PMID- 29947470
TI - A closed formula for calculating pesticide residue levels in the feed items of
terrestrial species.
AB - Calculating pesticide residue levels in feed items for terrestrial species
requires accounting for the application rate of the pesticide, the frequency and
interval of application, the half-life of the pesticide on the food item, and the
residue unit dose. Microsoft ExcelTM-based applications such as the US
Environmental Protection Agency's Terrestrial Residue Exposure model (T-REX) and
Terrestrial Herpetofaunal Exposure Residue Program (T-HERPS) calculate the
residue levels in feed items using a recursive sequence. A recursive sequence is
an unwieldy calculation method that presents a barrier to creating a software
based tool capable of conducting flexible assessments. Therefore, we determined
the closed form of the recursive mathematical equation used by both T-REX and T
HERPS. With this formula, we can both duplicate screening-level assessments (T
REX, T-HERPS) as well as incrementally refine the assessment with data-driven
inputs. Integr Environ Assess Manag 2018;14:703-709. (c) 2018 SETAC.
PMID- 29947473
TI - Refractory pityriasis rubra pilaris with good response after treatment with
ustekinumab.
PMID- 29947471
TI - Organs from deceased donors with false-positive HIV screening tests: An
unexpected benefit of the HOPE act.
AB - Organs from deceased donors with suspected false-positive HIV screening tests
were generally discarded due to the chance that the test was truly positive.
However, the HIV Organ Policy Equity (HOPE) Act now facilitates use of such
organs for transplantation to HIV-infected (HIV+) individuals. In the HOPE in
Action trial, donors without a known HIV infection who unexpectedly tested
positive for anti-HIV antibody (Ab) or HIV nucleic acid test (NAT) were
classified as suspected false-positive donors. Between March 2016 and March 2018,
10 suspected false-positive donors had organs recovered for transplant for 21 HIV
+ recipients (14 single-kidney, 1 double-kidney, 5 liver, 1 simultaneous liver
kidney). Median donor age was 24 years; cause of death was trauma (n = 5), stroke
(n = 4), and anoxia (n = 1); three donors were labeled Public Health Service
increased infectious risk. Median kidney donor profile index was 30.5 (IQR 22
58). Eight donors were HIV Ab+/NAT-; two were HIV Ab-/NAT+. All 10 suspected
false-positive donors were confirmed to be HIV-noninfected. Given the false
positive rates of approved assays used to screen > 20 000 deceased donors
annually, we estimate 50-100 HIV false-positive donors per year. Organ
transplantation from suspected HIV false-positive donors is an unexpected benefit
of the HOPE Act that provides another novel organ source.
PMID- 29947472
TI - Ex situ machine perfusion as a tool to recondition steatotic donor livers:
Troublesome features of fatty livers and the role of defatting therapies. A
systematic review.
AB - Long-standing research has shown that increased lipid content in donor livers is
associated with inferior graft outcomes posttransplant. The global epidemic that
is obesity has increased the prevalence of steatosis in organ donors, to the
extent that it has become one of the main reasons for declining livers for
transplantation. Consequently, it is one of the major culprits behind the
discrepancy between the number of donor livers offered for transplantation and
those that go on to be transplanted. Steatotic livers are characterized by poor
microcirculation, depleted energy stores because of an impaired capacity for
mitochondrial recovery, and a propensity for an exaggerated inflammatory response
following reperfusion injury culminating in poorer graft function
postoperatively. Ex situ machine perfusion, currently a novel method in graft
preservation, is showing great promise in providing a tool for the recovery and
reconditioning of marginal livers. Hence, reconditioning these steatotic livers
using machine perfusion has the potential to increase the number of liver
transplants performed. In this review, we consider the problematic issues
associated with fatty livers in the realm of transplantation and discuss
pharmacological and nonpharmacological options that are being developed to
enhance recovery of these organs using machine perfusion and defatting
strategies.
PMID- 29947474
TI - Comparative Bioavailability of Sildenafil 50-mg Film-Coated Tablets and 50-mg
Orally Disintegrating Films in Healthy Mexican Subjects: Results From a
Randomized, Open-Label, Crossover Study.
AB - An orally disintegrating film formulation of sildenafil 50 mg (CL Pharm Co, Ltd)
was used in this study and compared to the market-available product film coated
tablets (Viagra(r) , Pfizer, Mexico). The objective was to compare the
pharmacokinetic properties of these products after a single-dose administration
to 47 healthy male volunteers (aged 19-48 years) in a randomized, open-label, 2
way crossover study. Each subject received a single oral dose of 50 mg of
sildenafil test or reference product administered under fasting conditions at
each of the 2 study periods according to a crossover design. There was a 3-day
washout period between drug administrations. Blood samples for pharmacokinetic
analysis were collected predose and at different times postdosing. The maximum
plasma concentration and area under the curve from administration to last
observed concentration time of test and reference products were compared.
Pharmacokinetic parameters shown to be within the confidence interval 80% to 125%
for log-transformed data and Shuirmann and Anderson Hauck tests showed a high
probability that area under the curve values for the test product were within 80%
to 125% (P < .05). Adverse events occurred at similar rates for the 2
formulations (8 for each product), headache being the most prevalent. The results
suggest that the 2 sildenafil formulations, orally disintegrating films and film
coated tablets, are similar in terms of bioavailability, making the test product
a good alternative to treat erectile dysfunction and improving dosing
convenience.
PMID- 29947475
TI - Protective roles of estradiol against vascular oxidative stress in ovariectomized
female rats exposed to normoxia or intermittent hypoxia.
AB - AIM: We tested the hypothesis that estradiol (E2 ) reduces aortic oxidative
stress and endothelial dysfunction in ovariectomized (OVX) female rats exposed to
room air (RA) or chronic intermittent hypoxia (CIH). METHODS: We used intact or
OVX female rats treated with vehicle or E2 (0.5 mg/kg/d) and exposed to RA or CIH
(21%-10% O2 , 10 cycles/h, 8 h/d) for 7 or 35 days, and measured the arterial
pressure, heart rate and plasma endothelin-1 levels. We also measured in thoracic
aortic samples, the activities of the pro-oxidant enzymes NADPH (NOX) and
xanthine oxidase (XO), the antioxidant enzymes superoxide dismutase, catalase,
glutathione peroxidase and the advanced oxidation protein products (AOPP
oxidative stress marker). Finally, we used aortic rings to assess the contractile
response to phenylephrine and the vasodilatory response to acetylcholine.
RESULTS: After 7 or 35 days of CIH, E2 supplementation reduced arterial pressure.
E2 reduced plasma endothelin-1 levels after 7 days of CIH, but not after 35 days.
Ovariectomy, but not CIH for 7 days, increased aortic oxidative stress and E2
treatment prevented this effect. Remarkably, in animals exposed to RA, this was
achieved by a reduction in NOX and XO activities, but in animals exposed to CIH
this was achieved by increased catalase activity. In OVX female rats exposed to
CIH for 7 days, E2 supplementation improved the NO-mediated vasodilation. After
35 days of CIH, enzymatic activities, AOPP and aortic reactivity were similar in
all groups. CONCLUSION: E2 -based therapy could help prevent the vascular
consequences of CIH in apneic women.
PMID- 29947476
TI - An alternative evolutionary pathway for the twin-tail goldfish via szl gene
mutation.
AB - The twin-tail of ornamental goldfish provides unique evolutionary evidence that
the highly conserved midline localization of axial skeleton components can be
changed by artificial selection. This morphological change is known to be caused
by a nonsense mutation in one of the recently duplicated chordin genes, which are
key players in dorsal-ventral (DV) patterning. Since all of the multiple twin
tail ornamental goldfish strains share the same mutation, it is reasonable to
presume that this mutation occurred only once in domesticated goldfish. However,
zebrafish with mutated szl gene (another DV patterning-related gene) also exhibit
twin-tail morphology and higher viability than dino/chordin-mutant zebrafish.
This observation raises the question of whether the szl gene mutation could also
reproduce the twin-tail morphology in goldfish. Here we show that goldfish have
at least two subfunctionalized szl genes, designated szlA and szlB, and depletion
of these genes in single-fin goldfish was able to reproduce the bifurcated caudal
fin found in twin-tail ornamental goldfish. Interestingly, several phenotypes
were observed in szlA-depleted fish, while low expressivity of the twin-tail
phenotype was observed in szlB-depleted goldfish. Thus, even though szl gene
mutations may produce twin-tail goldfish, these szl gene mutations might not be
favorable for selection in domestic breeding. These results highlight the
uniqueness and rarity of mutations that are able to cause large-scale
morphological changes, such as a bifurcated axial skeleton, with high viability
and expressivity in natural and domesticated populations.
PMID- 29947477
TI - Clinical Pharmacokinetics and Drug-Drug Interaction Potential for Coadministered
SCY-078, an Oral Fungicidal Glucan Synthase Inhibitor, and Tacrolimus.
AB - SCY-078 is an orally bioavailable triterpenoid glucan synthase inhibitor in
clinical development as an intravenous and oral treatment of fungal infections
caused by Candida and Aspergillus species. This was a sequential, single-center,
open-label phase 1 study to assess the drug-drug interaction potential between
SCY-078 and tacrolimus during concomitant administration in healthy subjects. In
cohort 1, period 1, subjects received a single oral dose of tacrolimus 2 mg in
the fasted state. In period 2 after a >=15 day washout, subjects received a
single loading dose of SCY-078 1250 mg on day 1 followed by maintenance doses of
SCY-780 750 mg on days 2 through 8. On day 3 of period 2, subjects also received
a single dose of tacrolimus 2 mg concurrent with SCY-078. In cohort 2, subjects
received a loading dose of SCY-078 1250 mg on day 1 followed by maintenance doses
of SCY-780 750 mg on days 2 and 3. Pharmacokinetic (PK) parameters were compared
to assess both the impact of steady-state SCY-078 on tacrolimus and the impact of
tacrolimus on the PK of steady-state SCY-078. The concurrent coadministration of
tacrolimus and SCY-078 had no effect on the maximum blood levels of tacrolimus,
as evidenced by no change in maximum concentration of drug in blood plasma and a
1.4-fold increase in total area under the plasma drug concentration-time curve.
The concurrent coadministration of tacrolimus and SCY-078 resulted in a weaker
interaction than typically observed with the azole class of antifungals. The
current data indicate that an initial dose adjustment for tacrolimus may not be
warranted when combined with SCY-078, as the modest increase in exposure is less
than the therapeutic window, although tacrolimus monitoring, as with addition of
any new medication, is recommended. These results support the coadministration of
SCY-078 and tacrolimus.
PMID- 29947478
TI - Suicide Among Transgender and Gender-Nonconforming People.
AB - Suicide rates are higher in those who identify as transgender or gender
nonconforming (TGNC) compared to the overall population. Suicide risk factors
include discrimination, family rejection, internalized transphobia, and being
denied appropriate bathroom or housing access. It is important to assess the risk
of suicide among transgender and gender-nonconforming patients and discuss past
experiences of prejudice or maltreatment to prevent further victimization. This
narrative review includes the most pertinent literature from the past 17 years on
issues related to suicide among individuals who identify as TGNC. .
PMID- 29947479
TI - I Use "Wax" Because It Makes Me Calmer, But Now I Am Seeing 3D Images.
PMID- 29947480
TI - Cerebral Venous Thrombosis Following Strangulation.
PMID- 29947481
TI - Caffeine-Induced Psychosis in a Bodybuilder With Chronic Testosterone and
Amphetamine/Dextroamphetamine Misuse.
PMID- 29947482
TI - Supervision and assessment: the new Nursing and Midwifery Council standards.
AB - In the UK, mentors of pre-registration nurses must achieve the stage 2 outcomes
of the Nursing and Midwifery Council (NMC) ( 2008 ) standards to support learning
and assessment in practice. Approval for new standards for student supervision
and assessment was granted at the NMC meeting in March 2018 ( NMC 2018a ). The
introduction of the new standards will see the dissolution of mentorship and the
emergence of new roles to support students in academic and practice environments.
This article gives an overview of these standards and, drawing on the
recommendations from a collaborative event hosted by NHS Education for Scotland
and some of the findings from a rapid literature review undertaken for that
event, provides nurse managers with information to help inform their discussions
as they work in partnership with approved education institution colleagues to
realise, support and sustain the roles outlined in the new standards. The article
concludes with some questions to consider during these collaborative discussions.
PMID- 29947483
TI - [Pacemaker infection with Mycobacterium neoaurum].
PMID- 29947484
TI - Osteoarticular tuberculosis of the hip and soft tissues: images of a diagnostic
delay.
PMID- 29947485
TI - A 3-Years-Follow-Up Study of the Effect of the Weight Control Program on KAP and
Behavior among Overweight and Obese School Children in Nonthaburi Province.
AB - Objective: To evaluate the outcome of a program on behavioral change to control
weight on overweight and obese students at a primary school in 2013. The present
study aimed to find whether the Knowledge Attitude Practice (KAP) and behavior on
weight control from the behavioral change program were sustained. Material and
Method: This cross-sectional study was performed on overweight and obesity (OWOB)
students in a primary school between June 2013 and July 2016. At the first visit
in 2013, the affected students, parents, health education teachers, and food
retailers were educated about the Behavior Change Program. They were then given 3
month interventions. Weight and height of the participants were recorded before
and after interventions. The present study collected information on behaviors and
factors associated with weight control of the affected students and parents at
the two schools in July 2016 for comparison. Descriptive statistics, independent
t-test, and Chi-square test were used for analysis. Results: Review of the
Behavior Change Program in 2013 showed that after three months-interventions 18%
and 24% of 50 students had reduction and weight stability, respectively. The
present study could follow 45 students. The comparison group consists of 50
students from another school who were matched by private-own type included
capacity of the school, students of the same age group, and study classes. The
analysis showed that three years after the program, the intervention group had
more interest in weight control, and scored higher on food consumption behavior.
Parents of the intervention group were older, had higher education, chronic
illness, knowledge scores on food consumption and physical activities, and had
higher parental attitude scores. Conclusion: The behavior change program resulted
in 42% weight control. The present study found that sustained behavior and
significant factors were personal factor (interest to control weight), behavioral
factor about food consumption, and parental factors of older age, more chronic
illness, higher education, better knowledge on food consumption and physical
activities, and better attitude.
PMID- 29947486
TI - Delayed Therapeutic Response Time Predicts Renal Damage in the First Episode of
Febrile Urinary Tract Infection.
AB - Objective: To evaluate the relationship of therapeutic delay time (TDT) and
therapeutic response time (TRT) with renal damage in the first episode of febrile
urinary tract infection (UTI). Material and Method: A prospective study was
conducted in 67 children with the first episode of UTI at the Department of
Pediatrics, Faculty of Medicine Siriraj Hospital between 2008 and 2010. To assess
for renal damage, dimercaptosuccinic acid (DMSA) renal scintigraphy was performed
at one and six months after the acute episode. Results: Abnormal DMSA renal
scintigraphy was detected in 20 (29.9%) patients. There was no difference in TDT
but TRT was different between the patients with normal and abnormal DMSA renal
scintigraphy at p-value 0.001. The area under receiver operating characteristic
(ROC) curve for TRT was 0.76 (95% confidence interval (CI) 0.64-0.86) at p-value
0.001. The optimal cut-off value for TRT was 22 hours with sensitivity 80.0%
(56.3-94.1) and specificity 63.6% (47.8-77.6). In 50 patients with no
vesicoureteral reflux (VUR), there was difference in TRT at p-value 0.002. The
area under ROC curve for TRT was 0.82 (95% CI 0.69-0.96) at p-value 0.004. The
optimal cut-off value for TRT was 25 hours with sensitivity 88.9% (95% CI 51.7
98.2) and specificity 68.4% (95% CI 51.3- 82.5). Conclusion: TRT at or more than
22 hours predicts renal damage after first episode of UTI. In patients with no
VUR, TRT at or more than 25 hours predicts renal damage. DMSA renal scintigraphy
in the first episode of UTI should be considered in these patients.
PMID- 29947487
TI - Effectiveness of Intraperitoneal Bupivacaine in Reducing Postoperative Morphine
Used among Total Abdominal Hysterectomy Patients at Phramongkutklao Hospital.
AB - Objective: To study the effectiveness of intraperitoneal bupivacaine in reducing
24-hour postoperative morphine used in women underwent total abdominal
hysterectomy. Material and Method: Sixty-two non-malignant gynecologic patients,
aged 25 to 65 years, ASA class I-II, underwent elective total abdominal
hysterectomy. On the operative day, patients were allocated simple random
sampling. Blinded intraperitoneal solution was prepared and numbered for each
patient. In total, 40 ml of 0.25% bupivacaine solution or normal saline was
applied in the pelvic cavity after completed the operation. The abdominal muscle
and subcutaneous fat were infiltrated with 0.25% bupivacaine 10 ml each layer.
Intravenous morphine patient-controlled analgesia (PCA) was started in the
recovery room. The assessment of total morphine used, sedative score, numerical
rating score (NRS) for pain, postoperative nausea vomiting (PONV), pruritus, and
the number of vomiting and antiemetic drugs used were recorded at 1, 2, 4, 8, 12,
and 24 hours after intraperitoneal administration. Patients' satisfactory NRS was
evaluated after PCA cessation. Repeated measure ANOVA was used to compare means
between two groups. Baseline characteristics were calculated by descriptive
statistics, i.e., mean, standard deviation, median, and range. A p-value less
than 0.05 was considered statistically significant. Statistical package for the
social sciences (SPSS) for Windows version 23 was used. Results: There were no
significant differences were found between the two groups in general patients'
characteristics, intraoperative data, and anesthetic administration. Total
morphine consumption at 24 hours after intraperitoneal administration was
significantly less in the bupivacaine group than the saline group (25.03 vs.
16.13, p = 0.002). Lower pain score at 1 and 2 hours and significant difference
in reduced morphine consumption were observed within the first 4 hours after
intraperitoneal bupivacaine administration. Postoperative 24 hours satisfactory
score, PONV, pruritic score, overall incidences of vomiting and antiemetic use
were similar in both groups. Sedative scores were lower in the bupivacaine group
except at 1 and 24 hours postintraperitoneal administration. No evidence of local
anesthetic toxicity or operative complication was identified. Conclusion:
Administration of intraperitoneal and incisional 0.25% bupivacaine at the
completion of total abdominal hysterectomy produced a significant reduction in 24
hour postoperative morphine used without adverse effect.
PMID- 29947488
TI - Clinical Outcomes of Community-Acquired Severe Sepsis after Implementation of a
Simple Severe Sepsis Fast Track.
AB - Background: Severe sepsis and septic shock are the most common causes of in
hospital death in Songkhla Provincial Hospital and half of the patients are
transferred from community hospitals. A simple severe sepsis and septic shock
fast track had been implemented in all community hospitals in Songkhla Province
and in Songkhla Provincial Hospital in December 2013. Objective: Evaluate the
clinical outcomes and predictors of mortality of severe sepsis and septic shock
patients after implementation of the simple severe sepsis and septic shock fast
track. Material and Method: A retrospective study of all available medical
records between December 2013 and May 2014 of hospitalized patients aged older
than 15 years with a final diagnosis of severe sepsis or septic shock. Results:
Of 723 patients diagnosed as community acquired sepsis, 228 (31.5%) patients were
diagnosed with severe sepsis or septic shock. A simple severe sepsis and septic
shock fast track were activated in 69.3%. Patients in the activated fast track
group had significantly lower mortality than the non-activated fast track group
(21.0% vs. 42.9%, p = 0.001). After adjusted analysis, the four independent risk
factors associated with increased mortality in severe sepsis and septic shock
were initial presentation with systolic blood pressure lower than 90 mmHg
(adjusted odds ratio [aOR] 2.57), central nervous system failure (aOR 7.33),
acute renal failure (aOR 5.07), and received norepinephrine (aOR 2.87). Two
factors associated with a significant decrease in mortality were the simple fast
track activated at the emergency department (aOR 0.22) or at the ward (aOR 0.09)
and received appropriate initial antibiotics (aOR 0.09). Conclusion: Early
recognition and early resuscitation in case of severe sepsis and septic shock can
reduce mortality. A simple severe sepsis and septic shock fast track should be
implemented in all community hospitals. It is a simple clinical diagnosis with
simple management that is possible in every community hospital before transfer to
a secondary or tertiary care hospital.
PMID- 29947489
TI - Population Pharmacokinetics and Pharmacodynamics Modeling of Oral Levofloxacin.
AB - Background: Levofloxacin, a fluoroquinolone, is an isomer of ofloxacin with an
extensive spectrum of antimicrobial efficacy. In common with other
fluoroquinolones, the main pharmacokinetic/pharmacodynamic (PK/PD) index that
correlates with its therapeutic efficacy is the area under the plasma time
concentration curve (AUC)/the minimum inhibitory concentration (MIC) ratios.
Objective: To evaluate the population PK and determine the efficacy of various
dosage regimens in achieving the probability of target attainment (PTA) and the
cumulative fraction of response (CFR) of oral levofloxacin when prescribed as the
switching therapy after intravenous levofloxacin treatment. Material and Method:
The PK studies were conducted in 45 healthy volunteers who received one 500 mg
tablet of levofloxacin and PTAs were determined by using a Monte Carlo
simulation. The dosage regimens were predicted to achieve CFR greater than or
equal to 90% by referral to the MIC distributions database of the European
Committee on Antimicrobial Susceptibility Testing. Results: The population PKs of
levofloxacin were; the volume of distribution (V) = 101.71+/-1.41 L, total
clearance (CL) = 8.51+/-1.43 L/hour and the area under the plasma time
concentration curve from 0 to 24 hours (AUC0-24 ) = 66.19+/-1.30 mg*hour/L. The
predicted CFRs for a target AUC0-24 /MIC ratio of 30 for S. aureus and S.
pneumoniae were 83.12% and 92.63%, respectively for 500 mg levofloxacin, and
84.96% and 98.17%, respectively for 750 mg levofloxacin. The predicted CFRs for a
target AUC0-24 /MIC ratio of 125 for E. coli and Klebsiella spp. were 84.25% and
88.81%, respectively for 500 mg levofloxacin and 86.00% and 91.34%, respectively
for 750 mg levofloxacin. Conclusion: The population PKs of levofloxacin in the
present study were similar to the values obtained from the previous study. Both
500 mg qd and 750 mg qd of oral levofloxacin dosage regimens had a high
probability of achieving optimal impact against S. pneumoniae, but only the 750
mg qd dosage regimen achieved optimal exposure against Klebsiella spp.
PMID- 29947490
TI - Long-term, prolonged-release oral tapentadol for the treatment of refractory
chronic low back pain: a single-center, observational study.
AB - BACKGROUND: Chronic back pain is a leading cause of disability worldwide and it
is still inadequately treated. Tapentadol is a dual-acting analgesic drug MU
opioid receptor (MOR) agonist/norepinephrine reuptake inhibitor, carrying a lower
risk for opioid withdrawal symptoms and opioid-related adverse effects in
comparison to potent opioid drugs. This study investigates the effectiveness,
safety and tolerability of the prolonged release oral formulation of tapentadol
(tapentadol PR) in 27 patients affected by refractory chronic low back pain
during a long-term follow-up (up to 51 months). METHODS: This is an observational
study conducted at the Pain Therapy and Palliative Care Unit of University
Hospital of Cagliari, Italy. We enrolled 27 patients affected by chronic low back
pain refractory to other pharmacological treatments according to the inclusion
criteria. We prospectively evaluated oral tapentadol PR therapy during a long
term follow-up (up to 51 months) according to the following outcomes: pain
intensity during the previous 72 hours (Numeric Rating Scale 3), quality of life
(Short Form-12 Health Survey), self-reported treatment effectiveness (Patient
Global Impression of Change scale), physician evaluation of treatment
effectiveness (Clinician Global Impression of Change scale), treatment-related
adverse effects, reason for tapentadol therapy interruption and tapentadol
dosage. RESULTS: All the patients reported a significant improvement of pain
intensity and quality of life at the last follow-up. CONCLUSIONS: These results
show the long-term effectiveness, safety and tolerability of oral tapentadol PR
for the treatment of refractory chronic low back pain in a real-life clinical
setting.
PMID- 29947491
TI - Benign prostatic hypertrophy: Pycnogenol(r) supplementation improves prostate
symptoms and residual bladder volume.
AB - BACKGROUND: The aim of this study was to evaluate the efficacy of Pycnogenol(r)
supplementation in terms of safety and tolerability in the setting of preclinical
or borderline, initial symptoms of benign prostatic hyperthrophy (BPH), in
otherwise healthy subjects, using Pycnogenol(r) over a period of 60 days.
METHODS: Seventy-five healthy men with symptoms and signs of initial BPH were
included. The subjects were divided into three groups: 1) control group using
only the standard management (SM); 2) a group using SM plus Pycnogenol(r) 150
mg/day; 3) a group using standard pharmacological management. RESULTS: BPH
symptoms like emptying, frequency, intermittency, urgency, weak flow, straining,
nocturia, were all significantly improved with Pycnogenol(r) (P<0.05) and the
difference with both control groups was statistically significant (P<0.05).
CONCLUSIONS: Pycnogenol(r) may be an important option for self-management of BPH
in otherwise healthy men.
PMID- 29947492
TI - Quercetin phytosome(r) in triathlon athletes: a pilot registry study.
AB - BACKGROUND: Oxidative stress is associated with delayed recovery and higher risk
of post-training pain in triathlon athletes. Therefore, supplementation with
antioxidant compounds may have a role in enhancing recovery. Quercetin presents
marked antioxidant activity. In this pilot registry study, we evaluated the
effects of the supplementation with a novel proprietary delivery form
(phytosome(r)) of quercetin in amateur triathlon athletes. METHODS: We employed a
specific study model of triathlon according to the "Sprint" distance. The
individual triathlon training included repetition of the run 8 times in 14 days.
A group of athletes used quercetin phytosome(r) supplementation (one tablet of
250 mg quercetin phytosome(r) twice daily). A control group did not use
supplementation. All subjects attended a baseline measurement run and a second
final measurement run at day 14. At the end of the study, subjective performance,
post-training pain, cramps, time to full recovery and oxidative stress were
measured. RESULTS: In total, 23 subjects used the supplement and 25 did not. No
side effects were reported. The improvement of time to complete the run was
greater in subjects on quercetin supplementation compared with the control group
(-11.3% vs. -3.9%; P<0.05). Training was considered more valuable in the
quercetin group compared with controls (P<0.05). Similarly, post-run muscular
pain, cramps, localized pain and the post-exercise recovery time were all
considered better with the supplementation (P<0.05). Oxidative stress was also
reduced (P<0.05). CONCLUSIONS: This pilot study suggests that the oral
supplementation with quercetin phytosome(r) may result in improved training and
performance in amateur triathlon athletes.
PMID- 29947493
TI - Clodronate in the management of different musculoskeletal conditions.
AB - INTRODUCTION: Clodronic acid is a non-nitrogen-containing bisphosphonate largely
used from some decades in the prevention and treatment of postmenopausal and
secondary osteoporosis. In addition to antiresorptive activity, clodronate has
shown anti-inflammatory and analgesic properties, and modulatory effects on bone
and cartilage metabolism. EVIDENCE ACQUISITION: A literature review has been
conducted to characterize the mechanism of action of clodronate and to retrieve
available evidence about the use of clodronate in primary and secondary
osteoporosis, and its potential role in other musculoskeletal conditions and
orthopedic surgery. EVIDENCE SYNTHESIS: The efficacy and safety of the available
clodronate formulations (oral, intravenous and intramuscular) in the prevention
and treatment of postmenopausal and secondary osteoporosis, including
corticosteroid-induced osteoporosis and bone mass loss secondary to endocrine,
gastrointestinal and neoplastic diseases, have been demonstrated in a variety of
clinical trials. The analgesic, anti-inflammatory, bone- and chondro-modulating
properties of clodronate have allowed to expand its use in other musculoskeletal
conditions to those currently approved. Clodronate has proven to be beneficial in
the treatment of osteoarthritis of the knee and of the hand, in the management of
complex regional pain syndrome, and in the peri- and postoperative phase in
subjects undergoing arthroplasty. CONCLUSIONS: The analysis of the available
literature has shown that clodronate has relevant musculoskeletal effects beyond
the antiresorptive activity. Further research is needed to better position
clodronate therapy in the management of these conditions and to define the
optimal formulation and dose regimen in any of the tested new indications.
PMID- 29947494
TI - AVATAR(r): an electronic evidence-based medicine friendly tool for vascular
access planning.
AB - In today's demanding healthcare setting, many patients who are referred to
hospital for treatment require some form of intravascular access device to
administer required therapies and medications. It is estimated that most of
admissions have an intravascular device placed on arrival to any given facility.
Often these treatment prerequisites, combined with a wide range of available
devices, based upon a combination of patient assessments, necessitated treatment
regimens, and the use of a decision algorithm to choose the most appropriate
device that provides all the patient's needs, requires a logical and methodical
approach during the decision-making process. Several criteria should always
remain in high regard for patient and device considerations, such as overall need
for a device, the type of drugs or medications being infused, duration of
therapy, patient disease states and comorbidities, as well as vessel health,
patient age, previous intravascular device history, patient preference, potential
site(s) of implantation, and finally, the resources available for ongoing device
management. We have developed a tool, called AVATAR, aimed to make easier the
implementation of a vascular access planning. It is a newly-designed tool,
developed for the clinicians that must decide which type of venous access device
is the ideal one in each single patient. It utilizes existing information that
may not necessarily be only used by experts, but mainly by any clinician who may
be looking for assistance in determining patient requirements. It requires
clinical knowledge and it is not designed to be used for determining vascular
access choices in emergency situations.
PMID- 29947495
TI - Chronic venous disease: a comparison of real-life experiences.
PMID- 29947496
TI - The Development of Sleep Questionnaires Thai Version (ESS, SA-SDQ, and PSQI):
Linguistic Validation, Reliability Analysis and Cut-Off Level to Determine Sleep
Related Problems in Thai Population.
AB - Background: The Epworth Sleepiness Scale (ESS), Sleep Apnea Scale of Sleep
Disorders Questionnaire (SA-SDQ), and Pittsburgh Sleep Quality Index (PSQI) are
widely used in English speaking countries for sleep problem screening. However,
there is no officially validated Thai-version of sleep questionnaires available.
Objective: To provide standard Thai version of three sleep questionnaires and
find cut-off level to screening sleep problems in Thai population. Material and
Method: We used Mapi Research Institute Methods for translation from original
language to Thai questionnaire. Then, test-retest reliability analysis was
performed. Finally, we collected data from patients who underwent polysomnography
in Phramongkutklao Sleep Lab Centre between June and August 2011. Cut-off value
to screen population at risk for sleep-related disorder was researched. Results:
The questionnaires were translated with very good inter-rater agreement. Cut-off
of ESS, SA-SDQ, and PSQI suggested sleep disorders would be 9, 27, and 6.5
respectively. Conclusion: Sleep disorder questionnaires including ESS, SA-SDQ,
and PSQI were translated into Thai with high validity, reliability, and accuracy.
PMID- 29947497
TI - Unrecognized Delirium is Prevalent among Older Patients Admitted to General
Medical Wards and Lead to Higher Mortality Rate.
AB - Objective: Delirium is a syndrome associated with high mortality that often goes
undetected by healthcare providers. There has been limited evidence regarding the
consequences of under-recognition of delirium on patient outcomes. The present
study aimed to investigate the rate of under-recognized delirium and explore the
effect of unrecognized delirium on patient mortality. Material and Method: A
cohort of older patients aged 70 years or more who developed delirium during
admittance to general medical wards at Siriraj Hospital between January and March
2009 was retrospectively investigated. A diagnosis of delirium was made by
geriatricians applying DSM-IV criteria. Medical records were reviewed to identify
recognition of delirium by physicians and nurses. Factors affecting mortality
were investigated using univariate and multivariate logistic regression models.
Results: Of 110 patients who developed delirium, 57.3% of cases were identified
as delirium by physicians, with only 14.5% of cases having their delirium
documented in the discharge summary. Rate of delirium recognition among nurses
was 61.8%, with a comprehensive nursing care plan developed in only 13.6% of
cases. Patients with delirium that went unrecognized by attending physicians had
a mortality rate of 38.3%, compared to 15.9% for the recognized delirium group (p
= 0.008). In multivariate analysis, unrecognized delirium was identified as an
independent risk factor for death with adjusted OR of 5.16 (95% CI 1.45-18.29).
Conclusion: Rate of unrecognized delirium by healthcare providers in this study
was high, but comparable to previous studies. Moreover, under-recognition of
delirium was found to lead to higher mortality. Routine screening for delirium
and implementation of a proactive care plan by nurses for older patients admitted
to general medical wards might be a strategy for improving this common and
preventable medical condition and for lowering delirium-related mortality rates.
PMID- 29947498
TI - Serum Lactate Levels as a Prognostic Predictor of Septic Shock in Emergency
Department Patients with Systemic Inflammatory Response Syndrome (SIRS) at
Songklanagarind Hospital.
AB - Objective: To determine whether serum venous lactate is associated with an
increased risk of septic shock and risk of death in emergency department patients
with systemic inflammatory response syndrome (SIRS). Material and Method: This
was a prospective observational study at the Songklanagarind Hospital Emergency
Department. Between April 1 and October 31, 2009, 131 consecutive patients met
the enrollment criteria of age older than 18 years and fulfilled the SIRS
criteria. Serum venous lactate was obtained in all enrolled patients. The main
outcome measurements were development of septic shock, death within 24 hours, and
in-hospital mortality at 3- and 28-day of presentation. Results: Of the 131
patients enrolled, 50 (38.1%) developed septic shock. A lactate level greater
than 36 mg/dL was associated with death (odds ratio [OR] = 4.29, 95% confidence
interval [CI] = 1.19-15.55) to predict 28-day hospitalization mortality. It was
also statistically significant to the progression to septic shock (p = 0.013)
with 50.0% sensitivity and 73.2% specificity (OR = 2.73, 95% CI = 1.22-6.13).
Conclusion: For patients presenting to the emergency department with clinical
symptoms of SIRS, a single serum venous lactate level measurement of greater than
36 mg/dL provides valuable prognostic predictor information concerning the high
risk group likely to progress to septic shock, more serious disease severity, and
death.
PMID- 29947499
TI - A Ten to Thirteen Years Follow-up and Survivorship Study Cemented Low Contact
Stress (LCS) Total Knee Replacement in Thailand.
AB - Objective: The Low Contact Stress (LCS) rotating platform mobile-bearing knee
replacement is a leading, worldwide, knee replacement system, but has not been
the subject of long-term clinical and/or radiographic follow-up studies
evaluating the device in Thailand. The purpose of the present study was to report
the 13-year results of a consecutive series of patients who have had primary
total knee replacement performed implanting the LCS devices by a single surgeon,
Leelasestaporn C. Material and Method: Between May 1999 and December 2002, the
author performed 161 consecutive total knee arthroplasties in 138 patients with
LCS rotating-platform device by the Ethic Committee approval. All components were
cemented. The average age of the patients at the time of operation was 64.67
years old (range 47-84). One hundred twenty two patients (141 knees) were female,
and sixteen patients (20 knees) were male. Data analysis was performed
retrospectively on the 161 knees (138 patients) that were followed for more than
ten years. Kaplan-Meier survivorship curves were generated using revision as the
end point. The Knee Society Score (KSS) and range of motion (ROM) were evaluated
for clinical assessment and plane radiographs were used to evaluate implant
problems. Results: At the thirteen years follow-up, 101 patients (124 knees) were
alive, 13 patients (13 knees) died, and 24 patients (24 knees) were lost to
follow-up. Only one patient (1 knee) was revised during this period due to late
infection. The survivorship rate was 99.31% at 13 years for all knees, with an
average ROM of 127.08 degrees. The average knee score and function score at end
of follow-up were 98.62 and 98.69, respectively. Conclusion: The LCS system, in
Thailand, provides predictable results in tri-compartmental arthritis of the
knee, after 13 years follow-up with 99.31% survivorship rate or 100% survivorship
rate for aseptic loosening condition and excellent-knee society scores.
PMID- 29947500
TI - Assessing Caregiver Burden and Relationship between Caregiver Burden and Basic
Activities of Daily Living in Stroke Patients with Spasticity.
AB - Objective: To evaluate caregiver burden of stroke patients with spasticity and to
study the relationship between the caregiver burden and the ability to perform
basic activities of daily living (bADL) of these patients. Material and Method:
The study design was a cross-sectional descriptive research. The demographic data
of 52 stroke patients with spasticity and their caregivers at Songklanagarind
Hospital in Thailand were recorded. The Zarit Burden Interview (ZBI) in the Thai
version measured the caregiver burdens. The modified Barthel Index (BI) evaluated
the bADL of the patients. The correlation between the ZBI and modified BI were
calculated by The Spearman's rank correlation coefficient (rs) with p<0.05
considered as a significant level. Results: The caregivers were mainly female
(80.8%) who felt no burden (57%). The ZBI score did not significantly relate to
the modified BI in either the activity or total score. However, the ZBI score was
significantly associated to the caring hours per day (median 14 hours/day, rs =
0.37, p = 0.007) and left hemiparesis (p = 0.03). Conclusion: Most caregivers
realized that stroke survivors with spasticity were not a burden. There was no
relationship between the caregiver burden and the bADL of the patients, but the
burden was related to daily caregiving hours and stroke that affected the left
side of the body.
PMID- 29947501
TI - Factors Associated with Operating-Room Extubation after Emergency Craniotomy.
AB - Objective: To determine clinical factors and outcomes associated with operating
room extubation. Material and Method: Three hundred seventy three medical records
of emergency craniotomy were reviewed. The author categorized by whether the
patients underwent operating-room extubation (ORE) or not (nORE). Demographic and
perioperative factors were reviewed for association with ORE, e.g. Glasgow coma
scale score (GCS), brain edema, and duration of anesthesia. Outcomes included
clinical status, and duration in intensive care unit and hospital stay. Results:
Of the 373 patients, 130 (35%) had been extubated in the operating room. The
strongest factors associated with ORE were no perioperative brain edema (adjusted
odds ratio [OR] = 76.44 [95% confidence interval 9.46-617.50], p<0.001), high GCS
score from 13 to 15 (adjusted OR = 3.74 [1.99-7.01], p<0.001), and better ASA
physical class IE or IIE (adjusted OR = 2.09 [1.21-3.59], p = 0.008). The median
lengths of time in the intensive care unit (ICU) were significantly shorter among
OREs (3 days, range 2-5) than nOREs (4 days, range 3-8), p<0.001, as well as for
duration of hospital stay (7 days, range 4-10 vs. 8 days, range 5-13,
respectively, p = 0.008). Conclusion: After emergency neurosurgery, ORE is
associated with absent cerebral edema, high GCS score, and better ASA status.
PMID- 29947502
TI - Construction of Uniform Cobalt-Based Nanoshells and Its Potential for Improving
Li-Ion Battery Performance.
AB - Surface cobalt doping is an effective and economic way to improve the
electrochemical performance of cathode materials. Herein, by tuning the
precipitation kinetics of Co2+, we demonstrate an aqueous-based protocol to grow
uniform basic cobaltous carbonate coating layer onto different substrates, and
the thickness of the coating layer can be adjusted precisely in nanometer
accuracy. Accordingly, by sintering the cobalt-coated LiNi0.5Mn1.5O4 cathode
materials, an epitaxial cobalt-doped surface layer will be formed, which will act
as a protective layer without hindering charge transfer. Consequently, improved
battery performance is obtained because of the suppression of interfacial
degradation.
PMID- 29947503
TI - Nanostructure-Dependent Marcus-Type Correlation of the Shape Recovery Rate and
the Young's Modulus in Shape Memory Polymer Aerogels.
AB - Thermodynamic-kinetic relationships are not uncommon, but rigorous correlations
are rare. On the basis of the parabolic free-energy profiles of elastic
deformation, a generalized Marcus-type thermodynamic-kinetic relationship was
identified between the shape recovery rate, Rt( N), and the elastic modulus, E,
in poly(isocyanurate-urethane) shape memory aerogels. The latter were prepared
with mixtures of diethylene, triethylene, and tetraethylene glycol and an
aliphatic triisocyanate. Synthetic conditions were selected using a statistical
design of experiments method. Microstructures obtained in each formulation could
be put into two groups, one consisting of micron-size particles connected with
large necks and a second one classified as bicontinuous. The two types of
microstructures could be explained consistently by spinodal decomposition
involving early versus late phase separation relative to the gel point.
Irrespective of microstructure, all samples showed a shape memory effect with
shape fixity and shape recovery ratios close to 100%. Larger variations (0.35
0.71) in the overall figure of merit, the fill factor, were traced to a
variability in the shape recovery rates, Rt( N), which in turn were related to
the microstructure. Materials with bicontinuous microstructures were stiffer and
showed slower recovery rates. Thereby, using the elastic modulus, E, as a proxy
for microstructure, the correlation of Rt( N) with E was traced to a relationship
between the activation barrier for shape recovery, Delta A#, and the specific
energy of deformation, (reorganization energy, lambda), which in turn is
proportional to the elastic modulus. Data were fitted well ( R2 = 0.92) by the
derived equations. The inverse correlation between Rt( N) and the elastic
modulus, E, provides a means for qualitative predictability of the shape recovery
rates, the fill factors, and the overall quality of the shape memory effect.
PMID- 29947504
TI - A Multifunctional Metal-Organic Framework for Oxidative C-O Coupling Involving
Direct C-H Activation and Synthesis of Quinolines.
AB - A robust paddle-wheel Cu(II)-based metal-organic framework (MOF) 1, having dual
functionalities, namely, Lewis acid and basic sites, has been explored as a
heterogeneous catalyst. This MOF, because of its large void volume (10298 A3,
67.6%), large surface area (1480 m2/g), and high thermal stability, encouraged us
to see its applicability in two catalytic reactions, namely, oxidative C-O
coupling (cross-dehydrogentaive coupling reaction) involving direct C-H
activation and Friedlander reaction under solvent free and ambient conditions.
This study demonstrates the green aspect of MOFs in coupling reactions because of
the simplified recovery, shorter reaction time, minimum waste, and smooth
activation of the C-H bond, which is very challenging in synthetic chemistry.
PMID- 29947505
TI - Functionalization of Halloysite Nanotubes via Grafting of Dendrimer for Efficient
Intracellular Delivery of siRNA.
AB - Here, polyamidoamine grafted halloysite nanotubes (PAMAM- g-HNTs) were
synthesized for loading of siRNA in order to intracellular delivery of siRNA and
treat of breast cancer via gene therapy. The successful grafting of PAMAM on HNTs
was confirmed by various analytical methods. The size, zeta potential, and
grafting ratio of PAMAM- g-HNTs is ~206.2 nm, +19.8 mV, and 3.04%, respectively.
PAMAM- g-HNTs showed good cytocompatibility toward HUVECs (84.7%) and MCF-7 cells
(82.3%) even at high concentration of 100 MUg/mL. PAMAM- g-HNTs/siRNA exhibited
enhanced cellular uptake efficiency of 94.3% compared with Lipofectamine 2000
(Lipo2000)/siRNA (83.6%). PAMAM- g-HNTs/small interfering RNA-vascular
endothelial growth factor (siVEGF) led to 78.0% knockdown of cellular VEGF mRNA
and induced 33.6% apoptosis in the MCF-7 cells, which is also much higher than
that of Lipo2000/siVEGF. In vivo anti-cancer results demonstrated that PAMAM- g
HNTs/siVEGF treated 4T1-bearing mice showed enhanced anti-cancer efficacy than
Lipo2000/siVEGF group. Also, the nanocarrier system showed negligible toxic
effects toward the major organs of mice. In vivo fluorescence imaging studies
showed that there is a slight decrease in the fluorescence signal of PAMAM- g
HNTs/cy5-siVEGF after 72 h post-injection. Therefore, PAMAM- g-HNTs show
promising application as novel nanovectors for siRNA delivery and gene therapy of
cancer.
PMID- 29947506
TI - Emission Factors of Microbial Volatile Organic Compounds from Environmental
Bacteria and Fungi.
AB - Knowledge of the factors controlling the diverse chemical emissions of common
environmental bacteria and fungi is crucial because they are important signal
molecules for these microbes that also could influence humans. We show here not
only a high diversity of mVOCs but that their abundance can differ greatly in
different environmental contexts. Microbial volatiles exhibit dynamic changes
across microbial growth phases, resulting in variance of composition and emission
rate of species-specific and generic mVOCs. In vitro experiments documented
emissions of a wide range of mVOCs (>400 different chemicals) at high time
resolution from diverse microbial species grown under different controlled
conditions on nutrient media, or residential structural materials ( N = 54,
Ncontrol = 23). Emissions of mVOCs varied not only between microbial taxa at a
given condition but also as a function of life stage and substrate type. We
quantify emission factors for total and specific mVOCs normalized for respiration
rates to account for the microbial activity during their stationary phase. Our
VOC measurements of different microbial taxa indicate that a variety of factors
beyond temperature and water activity, such as substrate type, microbial
symbiosis, growth phase, and lifecycle affect the magnitude and composition of
mVOC emission.
PMID- 29947507
TI - Increasing Alkalinity Export from Large Russian Arctic Rivers.
AB - Riverine carbonate alkalinity (HCO3- and CO32-) sourced from chemical weathering
represents a significant sink for atmospheric CO2. Alkalinity flux from Arctic
rivers is partly determined by precipitation, permafrost extent, groundwater flow
paths, and surface vegetation, all of which are changing under a warming climate.
Here we show that over the past three and half decades, the export of alkalinity
from the Yenisei and Ob' Rivers increased from 225 to 642 Geq yr-1 (+185%) and
from 201 to 470 Geq yr-1 (+134%); an average rate of 11.90 and 7.28 Geq yr-1,
respectively. These increases may have resulted from a suite of changes related
to climate change and anthropogenic activity, including higher temperatures,
increased precipitation, permafrost thaw, changes to hydrologic flow paths,
shifts in vegetation, and decreased acid deposition. Regardless of the direct
causes, these trends have broad implications for the rate of carbon sequestration
on land and delivery of buffering capacity to freshwater ecosystems and the
Arctic Ocean.
PMID- 29947508
TI - Ag2Se to KAg3Se2: Suppressing Order-Disorder Transitions via Reduced
Dimensionality.
AB - We report an order-disorder phase transition in the 2D semiconductor KAg3Se2,
which is a dimensionally reduced derivative of 3D Ag2Se. At ~695 K, the room
temperature beta-phase (CsAg3S2 structure type, monoclinic space group C2/ m)
transforms to the high temperature alpha-phase (new structure type, hexagonal
space group R3 m, a = 4.5638(5) A, c = 25.4109(6) A), as revealed by in situ
temperature-dependent X-ray diffraction. Significant Ag+ ion disorder accompanies
the phase transition, which resembles the low temperature (~400 K) superionic
transition in the 3D parent compound. Ultralow thermal conductivity of ~0.4 W m-1
K-1 was measured in the "ordered" beta-phase, suggesting anharmonic Ag motion
efficiently impedes phonon transport even without extensive disordering. The
optical and electronic properties of beta-KAg3Se2 are modified as expected in the
context of the dimensional reduction framework. UV-vis spectroscopy shows an
optical band gap of ~1 eV that is indirect in nature as confirmed by electronic
structure calculations. Electronic transport measurements on beta-KAg3Se2 yielded
n-type behavior with a high electron mobility of ~400 cm2 V-1 s-1 at 300 K due to
a highly disperse conduction band. Our results thus imply that dimensional
reduction may be used as a design strategy to frustrate order-disorder phenomena
while retaining desirable electronic and thermal properties.
PMID- 29947510
TI - Putting Nanoarmors on Yolk-Shell Si@C Nanoparticles: A Reliable Engineering Way
To Build Better Si-Based Anodes for Li-Ion Batteries.
AB - : Practical utilization of silicon (Si) for Li-ion batteries (LIBs) still remains
sluggish because of its formidable kinetic problems of huge volume expansions
over 300%, instable solid electrolyte interphase (SEI), and unsatisfactory
electrical conductivity. Though using a yolk-shell (Y-S) Si@C nanodesign indeed
helps to mitigate active changes, optimize SEI properties, and lower intrinsic
charge-transfer impedances, the total anodic behaviors in reversibility, rate
capabilities, and long-lasting cyclability are still far from perfect. To settle
the above issues, we herein propose a reliable and effective way by putting tough
and malleable Ni nanoarmors on Y-S Si@C nanoparticles (Si@C?Ni). The unique
functionalized configurations endow such hybrid systems with superb reversible
capacity retention (almost no capacity decay emerges in 600 cycles, retaining a
reversible capacity beyond ~1307 mA h g-1), prominent cyclic stability, and rate
behaviors. To justify their potential usage, full cells of (-)Si@C?Ni//LiFePO4(+)
are further constructed, delivering impressive specific energy and power
densities (max. VALUES: ~423 W h kg-1/~497.8 W kg-1). This paradigm work may
offer a highly feasible engineering protocol to push forward Si anode
performances for next-generation LIBs.
PMID- 29947509
TI - Mn3O4 Quantum Dots Supported on Nitrogen-Doped Partially Exfoliated Multiwall
Carbon Nanotubes as Oxygen Reduction Electrocatalysts for High-Performance Zn-Air
Batteries.
AB - Highly efficient and low-cost nonprecious metal electrocatalysts that favor a
four-electron pathway for the oxygen reduction reaction (ORR) are essential for
high-performance metal-air batteries. Herein, we show an ultrasonication-assisted
synthesis method to prepare Mn3O4 quantum dots (QDs, ca. 2 nm) anchored on
nitrogen-doped partially exfoliated multiwall carbon nanotubes (Mn3O4 QDs/N-p
MCNTs) as a high-performance ORR catalyst. The Mn3O4 QDs/N-p-MCNTs facilitated
the four-electron pathway for the ORR and exhibited sufficient catalytic activity
with an onset potential of 0.850 V (vs reversible hydrogen electrode), which is
only 38 mV less positive than that of Pt/C (0.888 V). In addition, the Mn3O4
QDs/N-p-MCNTs demonstrated superior stability than Pt/C in alkaline solutions.
Furthermore, a Zn-air battery using the Mn3O4 QDs/N-p-MCNTs cathode catalyst
successfully generated a specific capacity of 745 mA h g-1 at 10 mA cm-2 without
the loss of voltage after continuous discharging for 105 h. The superior ORR
activity of Mn3O4 QDs/N-p-MCNTs can be ascribed to the homogeneous Mn3O4 QDs
loaded onto the N-doped carbon skeleton and the synergistic effects of Mn3O4 QDs,
nitrogen, and carbon nanotubes. The interface binding energy of -3.35 eV
calculated by the first-principles density functional theory method illustrated
the high stability of the QD-anchored catalyst. The most stable adsorption
structure of O2, at the interface between Mn3O4 QDs and the graphene layer, had
the binding energy of -1.17 eV, greatly enhancing the ORR activity. In addition
to the high ORR activity and stability, the cost of production of Mn3O4 QDs/N-p
MCNTs is low, which will broadly facilitate the real application of metal-air
batteries.
PMID- 29947511
TI - Pressure Effect Studies on the Spin Transition of Microporous 3D Polymer
[Fe(pz)Pt(CN)4].
AB - Pressure effects on the spin transition of the three-dimensional (3D) porous
coordination polymer {Fe(pz)[Pt(CN)4]} have been investigated in the interval 105
Pa-1.0 GPa through variable-temperature (10-320 K) magnetic susceptibility
measurements and spectroscopic studies in the visible region at room temperature.
These studies have disclosed a different behavior of the compound under pressure.
In the magnetic experiments, a temperature independent paramagnetic behavior has
been observed under 0.4 GPa. In contrast, at room temperature and at 0.8 GPa, a
complete HS-to-LS transition has been evidenced. The differences in the magnetic
behavior are strongly related with the porous structure of the compound and its
capability to adsorb the oil used as pressure transmission media in the magnetic
experiments.
PMID- 29947512
TI - Promoting Dual Electronic and Ionic Transport in PEDOT by Embedding Carbon
Nanotubes for Large Thermoelectric Responses.
AB - Thermoelectric (TE) energy conversion with nontraditional organic materials is
promising in wearable electronics and roll-to-roll manufacturing because of
mechanical flexibility, lightweight, and easy processing. Although typical
organic materials have a benefit of low thermal conductivity that creates a large
temperature gradient, relatively small thermopower (or Seebeck coefficient) often
requires copious number of TE legs to fabricate practical TE devices. Here, we
show that hybrids of poly(3,4-ethylenedioxythiophene)-tosylate (PEDOT-Tos) and
carbon nanotubes (CNTs) can produce extremely large thermopower, ~14 mV/K at room
temperature by a chemical reduction. With decent electrical conductivity, an
extraordinary power factor of ~1200 MUW/m K2 at room temperature was observed.
The large power factor could be attributed to prominent dual electronic and ionic
conduction, which is likely to be promoted by embedding the CNTs in PEDOT due to
the improvement in the carrier mobility, in comparison with the inferior and
widely varying TE properties of PEDOT-only samples in the literature. While a
higher CNT concentration gave a larger electronic contribution, a longer
reduction or a lower CNT concentration provided a larger ionic contribution.
Meanwhile, well-separated CNTs created CNT junctions intervened by PEDOT-Tos,
suppressing the thermal transport. Further research utilizing the high TE
responses could greatly help to develop practical wearable and/or mass-producible
thermal energy harvesting and storage devices.
PMID- 29947514
TI - Identification of Novel Functionally Important Aromatic Residue Interactions in
the Extracellular Domain of the Glycine Receptor.
AB - The extracellular domains (ECDs) of Cys-loop receptors contain many aromatic
amino acids, but only relatively few have been well studied. Here we explore the
roles of Tyr and Trp residues in the ECD of the glycine receptor and show that
four such residues that have not been previously studied (Y24, Y58, W170, and
Y197) contribute significantly to the function of the protein. The residues were
studied by creating mutant receptors, characterizing them using two-electrode
voltage clamp in Xenopus oocytes, and interpreting changes in receptor parameters
using structural information about the open and closed states of the receptor.
Alanine substitution of all these residues ablates function or increases the
glycine EC50. There are also a number of changes in the relative maximal
responses to taurine, a partial agonist, compared to glycine. Further mutations,
in combination with structural information, suggest Y24 contributes to an anion
pi interaction with a binding loop D residue, Y58 to an S-pi interaction
stabilizing the Cys loop, W170 to hydrophobic interactions stabilizing the
hydrophobic interior of the subunit, and Y197 to a hydrogen bond linking binding
loops B and C. These interactions appear to be broadly conserved in other Cys
loop receptors. Thus, we have identified new regions of the glycine receptor that
are important contributors to receptor activation and are likely also to
contribute to function in other members of this important protein family.
PMID- 29947513
TI - Intact Cell Lipidomics Reveal Changes to the Ratio of Cardiolipins to
Phosphatidylinositols in Response to Kanamycin in HeLa and Primary Cells.
AB - Antimicrobial resistance is a major threat the world is currently facing.
Development of new antibiotics and the assessment of their toxicity represent
important challenges. Current methods for addressing antibiotic toxicity rely on
measuring mitochondrial damage using ATP and/or membrane potential as a readout.
In this study, we propose an alternative readout looking at changes in the
lipidome on intact and unprocessed cells by matrix-assisted laser desorption
ionization mass spectrometry. As a proof of principle, we evaluated the impact of
known antibiotics (levofloxacin, ethambutol, and kanamycin) on the lipidome of
HeLa cells and mouse bone marrow-derived macrophages. Our methodology revealed
that clinically relevant concentrations of kanamycin alter the ratio of
cardiolipins to phosphatidylinositols. Unexpectedly, only kanamycin had this
effect even though all antibiotics used in this study led to a decrease in the
maximal mitochondrial respiratory capacity. Altogether, we report that intact
cell-targeted lipidomics can be used as a qualitative method to rapidly assess
the toxicity of aminoglycosides in HeLa and primary cells. Moreover, these
results demonstrate there is no direct correlation between the ratio of
cardiolipins to phosphatidylinositols and the maximal mitochondrial respiratory
capacity.
PMID- 29947515
TI - The "Missing" Bicarbonate in CO2 Chemisorption Reactions on Solid Amine Sorbents.
AB - We have identified a hydrated bicarbonate formed by chemisorption of 13CO2 on
both dimethylaminopropylsilane (DMAPS) and aminopropylsilane (APS) pendant
molecules grafted on SBA-15 mesoporous silica. The most commonly used sequence in
solid-state NMR, 13C CPMAS, failed to detect bicarbonate in these solid amine
sorbent samples; here, we have employed a Bloch decay ("pulse-acquire") sequence
(with 1H decoupling) to detect such species. The water that is present
contributes to the dynamic motion of the bicarbonate product, thwarting CPMAS but
enabling direct 13C detection by shortening the spin-lattice relaxation time.
Since solid-state NMR plays a major role in characterizing chemisorption
reactions, these new insights that allow for the routine detection of previously
elusive bicarbonate species (which are also challenging to observe in IR
spectroscopy) represent an important advance. We note that employing this
straightforward NMR technique can reveal the presence of bicarbonate that has
often otherwise been overlooked, as demonstrated in APS, that has been thought to
only contain adsorbed CO2 as carbamate and carbamic acid species. As in other
systems (e.g., proteins), dynamic species that sample multiple environments tend
to broaden as their motion is frozen out. Here, we show two distinct bicarbonate
species upon freezing, and coupling to different protons is shown through
preliminary 13C-1H HETCOR measurements. This work demonstrates that bicarbonates
have likely been formed in the presence of water but have gone unobserved by NMR
due to the nature of the experiments most routinely employed, a perspective that
will transform the way the sorption community will view CO2 capture by amines.
PMID- 29947516
TI - Association and Internal Morphology of Self-Assembled HPPhOx/BSA Hybrid
Nanoparticles in Aqueous Solutions.
AB - We investigate the formation of hybrid polyelectrolyte/protein nanoparticles by
associations between aggregates of partially hydrolyzed poly(2-phenyl-2
oxazoline) (HPPhOx) and bovine serum albumin (BSA) in aqueous solutions. Light
scattering experiments show that at conditions of low salt, BSA creates
interaggregate bridges and increases the size of the HPPhOx nanoparticles. At
high salt contents, breaking of aggregates leads to well-defined nanoparticles.
The interior of the formed nanoparticles is probed by small-angle neutron
scattering. At low salt, diffuse arrangements are observed, whereas at high salt
concentration, scattering is dominated by well-defined hydrophobic domains
enhanced by the incorporation of BSA. This system shows that the combination of
hydrophobic and electrostatic interactions in random-amphiphilic
polyelectrolyte/protein complexes can be used to determine the properties of self
assembled hybrid multifunctional nanoparticles.
PMID- 29947517
TI - Synthesis of Azolo[1,3,5]triazines via Rhodium(III)-Catalyzed Annulation of N
Azolo Imines and Dioxazolones.
AB - A wide range of azolo[1,3,5]triazines were obtained by Rh(III)-catalyzed
annulation of N-azolo imines and dioxazolones. The reaction proceeds by the first
catalytic C-H amidation of an imidoyl C-H bond followed by cyclodehydration. Good
yields were obtained for N-azolo imines derived from aminoazoles and aromatic and
heteroaromatic aldehydes. A range of dioxazolone amidating reagents were employed
to introduce aryl, heteroaryl, and alkyl substituents. The reaction was also
performed with a benchtop setup at 1 mmol scale using microwave heating.
PMID- 29947518
TI - Correction to Discovery of Bisubstrate Inhibitors of Nicotinamide N
Methyltransferase (NNMT).
PMID- 29947519
TI - Challenges in Transitioning Cocrystals from Bench to Bedside: Dissociation in
Prototype Drug Product Environment.
AB - Tablets containing a theophylline-glutaric acid (TG) cocrystal dissociated
rapidly forming crystalline theophylline (20-30%), following storage at 40
degrees C/75% RH for 2 weeks. Control tablets of TG cocrystal containing no
excipients were stable under the same conditions. The dissociation reaction was
water-mediated, and the theophylline concentration (the dissociation product),
monitored by synchrotron X-ray diffractometry, was strongly influenced by the
formulation composition. Investigation of the binary compacts of the TG cocrystal
with each excipient revealed the influence of excipient properties
(hydrophilicity, ionizability) on cocrystal stability, providing mechanistic
insights into a dissociation reaction. Ionizable excipients with a strong
tendency to sorb water, for example, sodium starch glycolate and croscarmellose
sodium, caused pronounced dissociation. Microcrystalline cellulose (MCC), while a
neutral but hydrophilic excipient, also enabled solution-mediated cocrystal
dissociation in intact tablets. Magnesium stearate, an ionizable but hydrophobic
excipient, interacted with the cocrystal to form a hygroscopic product. The
interaction is believed to be initiated in the disordered cocrystal-excipient
particle interface. In contrast, the cocrystal was stable in the presence of
lactose, a neutral excipient with no tendency to sorb water. The risk of
unintended cocrystal dissociation can be mitigated by avoiding contact with water
both during processing and storage.
PMID- 29947520
TI - Diastereoselective Synthesis of the Hydroperoxide-Keto Form of (+/-)-Steenkrotin
B.
AB - A diastereoselective approach for the synthesis of the hydroperoxide-keto form of
(+/-)-steenkrotin B (2') is described. The key features of the strategy involve a
Diels-Alder cycloaddition, a titanium(III)-catalyzed reductive annulation, and a
regio- and diastereoselective hydroperoxidation.
PMID- 29947521
TI - Unexpected [4 + 2] Cycloaddition through Chromium Non-Heteroatom-Stabilized
Alkynyl Carbene Complexes: Regioselective Access to Substituted 6-Azaindoles.
AB - A formal [4 + 2] heterocycloaddition of non-heteroatom-stabilized alkynyl carbene
complexes and iminopyrroles is described. The reaction implies a totally
regioselective synthesis of 6-azaindole derivatives through the formation of the
pyridine ring. The mechanism of the reaction has been explored by means of
density functional theory calculations, which showed a preference for the [4 + 2]
cycloaddition instead of the [2 + 2] or [3 + 3] cycloadditions observed with
other imines. The structure of the products also shows an unusual connectivity
pattern from carbene complexes.
PMID- 29947522
TI - Synthetic alpha- and beta-Ser-ADP-ribosylated Peptides Reveal alpha-Ser-ADPr as
the Native Epimer.
AB - A solid-phase methodology to synthesize oligopeptides, specifically incorporating
serine residues linked to ADP-ribose (ADPr), is presented. Through the synthesis
of both alpha- and beta-anomers of the phosphoribosylated Fmoc-Ser building block
and their usage in our modified solid-phase peptide synthesis protocol, both
alpha- and beta-ADPr peptides from a naturally Ser-ADPr containing H2B sequence
were obtained. With these, and by digestion studies using the human
glycohydrolase, ARH3 (hARH3), compelling evidence is obtained that the alpha-Ser
ADPr linkage comprises the naturally occurring configuration.
PMID- 29947523
TI - Chemoselective Photoredox Synthesis of Unprotected Primary Amines Using Ammonia.
AB - Unprotected alpha-amino carbon radicals are produced as novel intermediates via a
transformation that merges acid-promoted N-H imine generation and chemoselective
photocatalytic single-electron reduction. Coupling ammonia and aldehydes/ketones
allows the generation of primary amines under mild conditions without the need
for protecting groups. The key intermediate can be efficiently transformed into
primary (di)amines by a formal dimerization, reductive amination via hydrogen
atom transfer, and arylation through radical-radical coupling.
PMID- 29947524
TI - Two-Dimensional Crystallization of Poly( N-isopropylacrylamide)-Capped Gold
Nanoparticles.
AB - Surface-sensitive X-ray reflectivity and grazing incidence small-angle X-ray
scattering reveal the structure of polymer-capped-gold nanoparticles (AuNPs that
are grafted with poly( N-isopropylacrylamide); PNIPAM-AuNPs) as they self
assemble and crystallize at the aqueous suspension/vapor interface. Citrate
stabilized AuNPs (5 and 10 nm in nominal diameter) are ligand-exchanged by 6 kDa
PNIPAM-thiol to form corona brushes around the AuNPs that are highly stable and
dispersed in aqueous suspensions. Surprisingly, no clear evidence of
thermosensitive effect on surface enrichment or self-assembly of the PNIPAM-AuNPs
is observed in the 10-35 degrees C temperature range. However, addition of
simple salts (in this case, NaCl) to the suspension induces migration of the
PNIPAM-AuNPs to the aqueous surface, and above a threshold salt concentration,
two-dimensional crystals are formed. The 10 nm PNIPAM-AuNPs form a highly ordered
single layer with in-plane triangular structure, whereas the 5 nm capped NPs form
short-range triangular structure that gradually becomes denser as salt
concentration increases.
PMID- 29947525
TI - Au Nanoparticle-Catalyzed Insertion of Carbenes from alpha-Diazocarbonyl
Compounds into Hydrosilanes.
AB - Supported Au nanoparticles on TiO2 catalyze the insertion of carbenes from alpha
diazocabonyl compounds into hydrosilanes. It is proposed that the transformation
involves two modes of catalytic activation: formation of nucleophilic Au carbenes
on the surface of nanoparticle via expulsion of N2 and activation of the Si-H
bond of hydrosilane on Au nanoparticle, followed by coupling of the chemisorbed
species. No external ligands or additives are required, while the process is
purely heterogeneous, thus allowing the recycling and reuse of the catalyst.
PMID- 29947526
TI - In memoriam: Sidney George Shaw, DPhil (1948-2017).
AB - On March 4, 2017 at the age of 68, Sidney George Shaw (Sid) unexpectedly died
from complications following surgery, only four years after retiring from the
University of Bern. Trained in biochemistry at Oxford University, Sid had quickly
moved into molecular pharmacology and became a key investigator in the field of
enzyme biochemistry, vasoactive peptide research, and receptor signaling. Sid
spent half his life in Switzerland, after moving to the University of Bern in
1984. This article, written by his friends and colleagues who knew him and worked
with him during different stages of his career, summarizes his life, his
passions, and his achievements in biomedical research. It also includes personal
memories relating to a dear friend and outstanding scientist whose intellectual
curiosity, humility, and honesty will remain an example to us all.
PMID- 29947527
TI - New drugs and emerging therapeutic targets in the endothelin signaling pathway
and prospects for personalized precision medicine.
AB - During the last thirty years since the discovery of endothelin-1, the therapeutic
strategy that has evolved in the clinic, mainly in the treatment of pulmonary
arterial hypertension, is to block the action of the peptide either at the ET(A)
subtype or both receptors using orally active small molecule antagonists.
Recently, there has been a rapid expansion in research targeting ET receptors
using chemical entities other than small molecules, particularly monoclonal
antibody antagonists and selective peptide agonists and antagonists. While
usually sacrificing oral bio-availability, these compounds have other therapeutic
advantages with the potential to considerably expand drug targets in the
endothelin pathway and extend treatment to other pathophysiological conditions.
Where the small molecule approach has been retained, a novel strategy to combine
two vasoconstrictor targets, the angiotensin AT(1) receptor as well as the ET(A)
receptor in the dual antagonist sparsentan has been developed. A second emerging
strategy is to combine drugs that have two different targets, the ET(A)
antagonist ambrisentan with the phosphodiesterase inhibitor tadalafil, to improve
the treatment of pulmonary arterial hypertension. The solving of the crystal
structure of the ET(B) receptor has the potential to identify allosteric binding
sites for novel ligands. A further key advance is the experimental validation of
a single nucleotide polymorphism that has genome wide significance in five
vascular diseases and that significantly increases the amount of big endothelin-1
precursor in the plasma. This observation provides a rationale for testing this
single nucleotide polymorphism to stratify patients for allocation to treatment
with endothelin agents and highlights the potential to use personalized precision
medicine in the endothelin field.
PMID- 29947528
TI - Renoprotective effects of ET(A) receptor antagonists therapy in experimental non
diabetic chronic kidney disease: Is there still hope for the future?
AB - Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent
complication of diabetes, obesity and hypertension. Since it is typically
undetected for long periods, it often progresses to end-stage renal disease. CKD
is characterized by the development of progressive glomerulosclerosis,
interstitial fibrosis and tubular atrophy along with a decreased glomerular
filtration rate. This is associated with podocyte injury and a progressive rise
in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin
receptor type A (ET(A)) promotes renal cell injury, inflammation, and fibrosis
which finally lead to proteinuria, it is not surprising that ET(A) receptors
antagonists have been proven to have beneficial renoprotective effects in both
experimental and clinical studies in diabetic and non-diabetic CKD.
Unfortunately, fluid retention encountered in large clinical trials in diabetic
CKD led to the termination of these studies. Therefore, several advances,
including the synthesis of new antagonists with enhanced pharmacological
activity, the use of lower doses of ET antagonists, the addition of diuretics,
plus simply searching for distinct pathological states to be treated, are
promising targets for future experimental studies. In support of these
approaches, our group demonstrated in adult subtotally nephrectomized Ren-2
transgenic rats that the addition of a diuretic on top of renin-angiotensin and
ET(A) blockade led to a further decrease of proteinuria. This effect was
independent of blood pressure which was normalized in all treated groups. Recent
data in non-diabetic CKD, therefore, indicate a new potential for ET(A)
antagonists, at least under certain pathological conditions.
PMID- 29947529
TI - Increased endothelin-1-mediated vasoconstrictor tone in human obesity: effects of
gut hormones.
AB - The heavy impact of obesity on the development and progression of cardiovascular
disease has sparked sustained efforts to uncover the mechanisms linking excess
adiposity to vascular dysfunction. Impaired vasodilator reactivity has been
recognized as an early hemodynamic abnormality in obese patients, but also
increased vasoconstrictor tone importantly contributes to their vascular damage.
In particular, upregulation of the endothelin (ET)-1 system, consistently
reported in these patients, might accelerate atherosclerosis and its
complication, given the pro-inflammatory and mitogenic properties of ET-1. In
recent years, a number of gut hormones, in addition to their role as modulators
of food intake, energy balance, glucose and lipid metabolism, and insulin
secretion and action, have demonstrated favorable vascular actions. They increase
the bioavailability of vasodilator mediators like nitric oxide, but they have
also been shown to inhibit the ET-1 system. These features make gut hormones
promising tools for targeting both the metabolic and cardiovascular complications
of obesity, a view supported by recent large-scale clinical trials indicating
that novel drugs for type 2 diabetes with cardiovascular potential may translate
into clinically significant advantages. Therefore, there is real hope that better
understanding of the properties of gut-derived substances might provide more
effective therapies for the obesity-related cardiometabolic syndrome.
PMID- 29947530
TI - Endothelin and diabetic complications: a brain-centric view.
AB - The global epidemic of diabetes is of significant concern. Diabetes associated
vascular disease signifies the principal cause of morbidity and mortality in
diabetic patients. It is also the most rapidly increasing risk factor for
cognitive impairment, a silent disease that causes loss of creativity,
productivity, and quality of life. Small vessel disease in the cerebral
vasculature plays a major role in the pathogenesis of cognitive impairment in
diabetes. Endothelin system, including endothelin-1 (ET-1) and the receptors
(ET(A) and ET(B)), is a likely candidate that may be involved in many aspects of
the diabetes cerebrovascular disease. In this review, we took a brain-centric
approach and discussed the role of the ET system in cerebrovascular and cognitive
dysfunction in diabetes.
PMID- 29947531
TI - A novel neuroregenerative approach using ET(B) receptor agonist, IRL-1620, to
treat CNS disorders.
AB - Endothelin B (ET(B)) receptors present in abundance the central nervous system
(CNS) have been shown to have significant implications in its development and
neurogenesis. We have targeted ET(B) receptors stimulation using a highly
specific agonist, IRL-1620, to treat CNS disorders. In a rat model of cerebral
ischemia intravenous administration IRL-1620 significantly reduced infarct volume
and improved neurological and motor functions compared to control. This
improvement, in part, is due to an increase in neuroregeneration. We also
investigated the role of IRL-1620 in animal models of Alzheimer's disease (AD).
IRL-1620 improved learning and memory, reduced oxidative stress and increased
VEGF and NGF in Abeta treated rats. IRL-1620 also improved learning and memory in
an aged APP/PS1 transgenic mouse model of AD. These promising findings prompted
us to initiate human studies. Successful chemistry, manufacturing and control
along with mice, rat and dog toxicological studies led to completion of a human
Phase I study in healthy volunteers. We found that a dose of 0.6 microg/kg of IRL
1620 can be safely administered, three times every four hours, without any
adverse effect. A Phase II clinical study with IRL-1620 has been initiated in
patients with cerebral ischemia and mild to moderate AD.
PMID- 29947532
TI - Endothelin-1 regulation is entangled in a complex web of epigenetic mechanisms in
diabetes.
AB - Endothelial cells (ECs) are primary targets of glucose-induced tissue damage. As
a result of hyperglycemia, endothelin-1 (ET-1) is upregulated in organs affected
by chronic diabetic complications. The objective of the present study was to
identify novel transcriptional mechanisms that influence ET-1 regulation in
diabetes. We carried out the investigation in microvascular ECs using multiple
approaches. ECs were incubated with 5 mM glucose (NG) or 25 mM glucose (HG) and
analyses for DNA methylation, histone methylation, or long non-coding RNA-
mediated regulation of ET-1 mRNA were then performed. DNA methylation array
analyses demonstrated the presence of hypomethylation in the proximal promoter
and 5' UTR/first exon regions of EDN1 following HG culture. Further, globally
blocking DNA methylation or histone methylation significantly increased ET-1 mRNA
expressions in both NG and HG-treated HRECs. While, knocking down the
pathogenetic lncRNAs ANRIL, MALAT1, and ZFAS1 subsequently prevented the glucose
induced upregulation of ET-1 transcripts. Based on our past and present findings,
we present a novel paradigm that reveals a complex web of epigenetic mechanisms
regulating glucose-induced transcription of ET-1. Improving our understanding of
such processes may lead to better targeted therapies.
PMID- 29947533
TI - Nephron prorenin receptor deficiency alters renal medullary endothelin-1 and
endothelin receptor expression.
AB - The endothelin (ET) and prorenin/renin/prorenin receptor (PRR) systems have
opposing physiological effects on collecting duct (CD) salt and water
reabsorption. It is unknown if the CD ET and renin/PRR systems interact, hence we
examined the effects of deleting CD renin or nephron PRR on CD ET system
components. PRR knockout (KO) mice were polyuric and had markedly increased
urinary ET-1 and inner medullary CD (IMCD) ET-1 mRNA. PRR KO mice had greatly
increased IMCD ETA receptor mRNA and protein, while ETB mRNA and protein were
decreased. Water loaded wild-type mice with similar polyuria as PRR KO mice had
modestly increased urinary ET-1 excretion and inner medullary ET-1 mRNA, while
inner medullary ETA and ETB mRNA or protein expression were unaffected. In
contrast to PRR KO, CD prorenin/renin KO did not alter ET system components.
Taken together, these results suggest that the nephron PRR is involved in
regulating CD ET system expression, but this effect may be independent of CD
derived renin.
PMID- 29947534
TI - Vitamin D upregulates endothelin-1, ETBR, eNOS mRNA expression and attenuates
vascular remodelling and ischemia in kidney fibrosis model in mice.
AB - We examined the upregulation of ET-1/ETBR/eNOS signaling in renoprotective effect
of vitamin D in kidney fibrosis model in mice using unilateral ureteral
obstruction (UUO). One group was treated with intraperitoneal injection of 0.125
mg/kg of Calcitriol (UUO+VD). Vascular remodeling was quantified based on lumen
area and lumen/wall area ratio (LWAR) of intrarenal arteries using Sirius Red
staining. ET-1, ETBR, eNOS, CD31 and VEGF mRNA expressions were quantified using
qRT-PCR. Focusing on endothelin-1 (ET-1) signaling in endothelial cells (EC),
siRNA of ET-1 was performed in human umbilical vein endothelial cells (HUVEC) for
reducing ET-1 expression. Then HUVECs were treated with and without 100 nM
Calcitriol treatment in hypoxic and normoxic conditions to elucidate ET-1/eNOS
signaling. Our in vivo study revealed vascular remodeling and renal ischemia
attenuation after Calcitriol treatment. Vascular remodeling was attenuated in the
UUO+VD group as shown by increasing lumen areas and LWAR in intrarenal arteries.
These findings were associated with significant higher CD31 and VEGF mRNA
expression compared to the UUO group. Vitamin D treatment also increased ET-1,
ETBR and eNOS mRNA expressions. Our in vitro study demonstrated Calcitriol
induced ET-1 and eNOS mRNA expressions upregulation in HUVEC under normoxic and
hypoxic condition. Meanwhile, siRNA for ET-1 inhibited the upregulation of eNOS
mRNA expression after Calcitriol treatment. Vitamin D ameliorates kidney fibrosis
through attenuating vascular remodeling and ischemia with upregulating ET-1/ETBR
and eNOS expression.
PMID- 29947535
TI - Natriuretic response to renal medullary endothelin B receptor activation is
impaired in Dahl-salt sensitive rats on a high-fat diet.
AB - Renal medullary endothelin B receptors (ET(B)) mediate sodium excretion and blood
pressure (BP) control. Several animal models of hypertension have impaired renal
medullary ET(B) function. We found that 4-week high-caloric diet elevated
systolic BP in Dahl salt-sensitive (Dahl S) rats (126+/-2 vs. 143+/-3 mm Hg,
p<0.05). We hypothesized that renal medullary ET(B) function is dysfunctional in
DS rats fed a high-caloric diet. We compared the diuretic and natriuretic
response to intramedullary infusion of ET(B) agonist sarafotoxin 6c (S6c) in DS
rats fed either a normal or high-caloric diet for 4 weeks. Urine was collected
during intramedullary infusion of saline for baseline collection followed by
intramedullary infusion of either saline or S6c. We first examined the ET(B)
function in DS rats fed a normal diet. S6c increased urine flow (2.7+/-0.3
microl/min during baseline vs. 5.1+/-0.6 microl/min after S6c; p<0.05; n=5) and
sodium excretion (0.28+/-0.05 vs. 0.81+/-0.17 micromol/min; p<0.05), suggesting
that DS rats have renal medullary ET(B) function. However, DS rats fed a high
caloric diet displayed a significant increase in urine flow (2.7+/-0.4 vs. 4.2+/
0.4 microl/min, baseline vs. S6c infusion, respectively; p<0.05, n=6), but no
significant change in sodium excretion in response to S6c (0.32+/-0.06 vs. 0.45+/
0.10 micromol/min). These data demonstrate that renal medullary ET(B) function is
impaired in DS rats fed a high-caloric diet, which may be contributed to the
elevation of blood pressure during high-caloric feeding in this model.
PMID- 29947536
TI - Effects of resistance training on arterial compliance and plasma endothelin-1
levels in healthy men.
AB - Arterial compliance (AC) is an index of the elasticity of large arteries.
Endothelial dysfunction has been reported to result in reduced arterial
compliance, which represents increased arterial stiffness. A reduction in AC is
elicited by high-intensity resistance training, however the mechanisms are
obscure. Because a single bout of resistance exercise causes a transient increase
in circulating plasma endothelin-1 in humans, some vasoconstrictors may play a
role in the mechanisms. The present study aimed to investigate whether resistance
training-induced decrease in AC is associated with changes in circulating
vasoconstrictors levels in young men. Young sedentary men were assigned to
control (n=5) or training (n=9) groups. The training group performed four-week
high-intensity resistance training (weight training exercise; three
sessions/week). We measured AC and plasma levels of endothelin-1, angiotensin II,
and norepinephrine before and after intervention. Resistance training
significantly decreased AC, whereas the changes in plasma levels of neither
endothelin-1, nor angiotensin II, nor norepinephrine were significantly different
between the control and the training groups. Moreover, we found no significant
correlations between changes in circulating plasma levels (endothelin-1,
angiotensin II, and norepinephrine) and in the AC. Despite of no alteration of
the resting circulating plasma levels (endothelin-1, etc.), we cannot exclude a
possibility that the tissue/local concentrations of vasoconstrictors (endothelin
1, etc.) around the vessels might be increased and also involved in a reduction
of AC in the training group. Taken together, the present results suggest that
circulating vasoconstrictors (endothelin-1, etc.) in plasma are not involved in a
reduction in AC by the resistance training.
PMID- 29947538
TI - The glucagon-like peptide-1 receptor agonist liraglutide improves hypoxia-induced
pulmonary hypertension in mice partly via normalization of reduced ET(B) receptor
expression.
AB - The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin
hormone mimetic used in the treatment of diabetes. However, the effects of
liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system
are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle
for 5 weeks. One week after injection, the mice were exposed to either room air
(normoxia) or chronic hypoxia (10 % O(2)) for 4 weeks. The right ventricular
systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than
in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable
among all the groups. ET(B) mRNA and protein expression in the lungs was
significantly lower in hypoxia + vehicle group than in normoxia + vehicle group.
The above changes were normalized by liraglutide treatment. The expression of
phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in
hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for
the first time that liraglutide effectively improved RVSP and RV hypertrophy in
hypoxia-induced PH mice by activating eNOS through normalization of impaired
ET(B) pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be
promising therapeutic agents for PH.
PMID- 29947537
TI - Endothelin A receptor blockade improves endothelium-dependent relaxation in obese
woman.
AB - Hypertension in obesity is associated with increased insulin resistance, vascular
mass and body mass index (BMI). The purpose of the study was to visualize
endothelin-1 (ET-1) mediated constriction in arteries isolated from subcutaneous
adipose tissue from obese hypertensive women previously operated by gastric
bypass. Functional studies were conducted in a microvascular myograph. Expressed
as percentage of contraction elicited by 124 mM KCl concentration-response curves
for ET-1 were shifted leftward in arteries from obese hypertensive patients
compared to healthy normotensive subjects. The vasodilator response to the ET-1
antagonist BQ123 (1 microM) was significantly higher in arteries from obese
hypertensive patients (p<0.001). BQ123 induced relaxation was inhibited by NO
synthase inhibitor L-NAME (0.1 nM). Preincubation with BQ123 enhanced the
relaxation induced by acetylcholine (ACh; 0.1 nM - 0.1 mM) (p<0.001), but not
that induced by NO donor sodium nitroprusside (SNP; 0.1 nM - 0.1 mM), in arteries
from obese hypertensive patients. The present study show that hypertension yet
prevail after gastric bypass surgery and the ET(A) receptor antagonist BQ123 may
be a useful tool in reducing blood pressure in obese hypertensive patients.
PMID- 29947539
TI - Endothelial-derived endothelin-1 promotes pulmonary vascular remodeling in
bleomycin-induced pulmonary fibrosis.
AB - Endothelin-1 (ET-1) induces pulmonary vascular remodeling and pulmonary
hypertension secondary to pulmonary fibrosis. Given that endothelial cells are
the main source of ET-1 and ET-1 from other cells may encounter difficulty
penetrating vascular compartments, we hypothesize that endothelial-derived ET-1
promotes vascular remodeling secondary to pulmonary fibrosis. We used vascular
endothelial ET-1 knock-out (VEETKO) and Wild type mice for this research. They
were given intratracheal bleomycin and euthanized at day 28. We quantified
pulmonary fibrosis, measured lung ET-1 and its receptors' expression, and
assessed pulmonary vascular remodeling by calculating medial wall index,
muscularization index, adventitial collagen and adventitial fibroblast and
macrophage accumulation. Right ventricle remodeling was also assessed. Both
VEETKO and Wild type mice developed comparable pulmonary fibrosis and similar
fibrosis-related gene expression. Compared to Wild type mice, bleomycin-induced
VEETKO mice had lower ET-1 peptide levels (15.4 pg/mg vs. 31.2 pg/mg, p<0.01).
Expression of both ET-1 receptors mRNAs were increased in fibrosis models.
Bleomycin-induced fibrosis VEETKO mice had significantly less muscularized
arterioles, lower muscularization index and attenuated adventitial collagen,
fibroblast and macrophage accumulation as compared to that of Wild type mice.
Right ventricular pressure, hypertrophy and fibrosis did not increase both in
VEETKO and Wild type mice despite the more enhanced vascular remodeling in Wild
type. In conclusion, endothelial-derived endothelin-1 promotes pulmonary vascular
remodeling secondary to bleomycin-induced pulmonary fibrosis.
PMID- 29947540
TI - Alterations in endothelin receptors following hemorrhage and resuscitation by
centhaquin.
AB - Endothelin-1 (ET-1) acts on ET(A) and ET(B) receptors and has been implicated in
hemorrhagic shock (shock). We determined effect of shock and resuscitation by
hypertonic saline (saline) or centhaquin on ET(A) and ET(B) receptor expression.
Rats were anesthetized, a pressure catheter was placed in the left femoral
artery; blood was withdrawn from the right femoral artery to bring mean arterial
pressure (MAP) to 35 mm Hg for 30 min, resuscitation was performed and 90 min
later sacrificed to collect samples for biochemical estimations. Resuscitation
with centhaquin decreased blood lactate and increased MAP. Protein levels of
ET(A) or ET(B) receptor were unaltered in the brain, heart, lung and liver
following shock or resuscitation. In the abdominal aorta, shock produced an
increase (140 %) in ET(A) expression which was attenuated by saline and
centhaquin; ET(B) expression was unaltered following shock but was increased (79
%) by centhaquin. In renal medulla, ET(A) expression was unaltered following
shock, but was decreased (-61 %) by centhaquin; shock produced a decrease (-34 %)
in ET(B) expression which was completely attenuated by centhaquin and not saline.
Shock induced changes in ET(A) and ET(B) receptors in the aorta and renal medulla
are reversed by centhaquin and may be contributing to its efficacy.
PMID- 29947541
TI - Interactions of peripheral endothelin-1 and nerve growth factor as contributors
to persistent cutaneous pain.
AB - Endothelin-1 (ET-1) and Nerve Growth Factor (NGF) are proteins, released from
cancer-ridden tissues, which cause spontaneous pain and hypersensitivity to
noxious stimuli. Here we examined the electrophysiological and behavioral effects
of these two agents for evidence of their interactions. Individual small-medium
cultured DRG sensory neurons responded to both ET-1 (50 nM, n=6) and NGF (100
ng/ml, n=4), with increased numbers of action potentials and decreased slow K(+)
currents; pre-exposure to ET-1 potentiated NGF's actions, but not vice versa.
Behaviorally, single intraplantar (i.pl.) injection of low doses of ET-1 (20
pmol) or NGF (100 ng), did not increase hindpaw tactile or thermal sensitivity,
but their simultaneous injections sensitized the paw to both modalities. Daily
i.pl. injections of low ET-1 doses in male rats caused tactile sensitization
after 21 days, and enabled further tactile and thermal sensitization from low
dose NGF, in ipsilateral and contralateral hindpaws. Single injections of 100 ng
NGF, without changing the paw's tactile sensitivity by itself, acutely sensitized
the ipsilateral paw to subsequent injections of low ET-1. The sensitization from
repeated low ET-1 dosing and the cross-sensitization between NGF and ET-1 were
both significantly greater in female than in male rats. These findings reveal a
synergistic interaction between cutaneously administered low doses of NGF and ET
1, which could contribute to cancer-related pain.
PMID- 29947542
TI - Lipopolysaccharide-induced necroptosis of brain microvascular endothelial cells
can be prevented by inhibition of endothelin receptors.
AB - Over activation of the endothelin-1 (ET-1) system in disease states contributes
to endothelial dysfunction. On the other hand, ET-1 promotes proliferation and
survival of endothelial cells. Regulation of programmed cell death (PCD) pathways
is critical for cell survival. Recently discovered necroptosis (regulated
necrosis) is a pathological PCD mechanism mediated by the activation of toll like
receptor 4 (TLR4), which also happens to stimulate ET-1 production in dendritic
cells. To establish the effect of ET-1 on PCD and survival of human brain
microvascular endothelial cells (BMVECs) under control and inflammatory
conditions, BMVECs were treated with ET-1 (10 nM, 100 nM and 1 microM) or
lipopolysaccharide (LPS, 100 ng/ml). ET receptors were blocked with bosentan (10
microM). Under normal growth conditions, exogenous ET-1 reduced BMVEC viability
and migration at a relatively high concentration (1 microM). This was accompanied
with activation of necroptosis and apoptosis marker genes. LPS decreased
endogenous ET-1 secretion, increased ET(B) receptor expression and activated
necroptosis. Even though ET-1 levels were low (less than 10 nM levels used under
normal growth conditions), blocking of ET receptors with bosentan inhibited the
necroptosis pathway and improved the cell migration ability of BMVECs, suggesting
that under inflammatory conditions, ET-1 activates PCD pathways in BMVECs even at
physiological levels.
PMID- 29947543
TI - Endothelin-1 inhibition improves the mBDNF/proBDNF ratio in endothelial cells and
HT22 neurons under high glucose/palmitate growth conditions.
AB - Diabetes increases the risk and worsens the progression of cognitive impairment.
The hippocampus is an important domain for learning and memory. We previously
showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in
hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and
endothelial cells within the neurovascular unit depend on each other for proper
function, we investigated the effect of ET-1 on brain-derived neurotrophic factor
(BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22
hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under
normal and diabetes-mimicking (high glucose plus palmitate) conditions. Cells
were treated with exogenous ET-1 or ET receptor antagonists including ET(B)
receptor selective antagonist BQ788 (1 microM) or dual-receptor antagonist
bosentan (10 microM). Mature (m)BDNF, proBDNF and caspase-3 levels were measured
by Western blotting. Diabetic conditions reduced the prosurvival mBDNF/proBDNF
ratio in both HT22 and BMEC-5i cells. Addition of exogenous ET-1 had no effect on
the BDNF system in HT22 cells in diabetic conditions. Both HT22 and BMEC-5i cells
had an increase in the mBDNF/proBDNF ratio when grown in diabetes-simulating
conditions in the presence of endothelin receptor inhibition. These data suggest
that blockade of ET-1 may provide neuroprotection to hippocampal cells through
the modulation of the BDNF system.
PMID- 29947544
TI - Temporal changes of the endothelin system in human cytotrophoblasts during the
first trimester of pregnancy.
AB - The first trimester of pregnancy is characterized by continuous proliferation,
invasion and differentiation of cytotrophoblasts. These processes are precisely
controlled both, in space and time by molecules such as endothelin-1 (ET-1). ET-1
is expressed in human first trimester trophoblast and is known to stimulate
cytotrophoblast proliferation through endothelin A and B receptor subtypes (ET(A)
and ET(B)), and cytotrophoblast invasion through ET(B). However, temporal changes
of the ET system during the first trimester of pregnancy have not been previously
studied. This study tested the hypothesis that ET-1 release, ET(A) and ET(B)
expression are increased towards the end of the first trimester of pregnancy
(weeks 10-12 vs. weeks 6-9), resulting in increased cytotrophoblast proliferation
and invasion. Tissue samples were obtained from 17 surgical pregnancy
interruptions (week 6-9: n=9; week 10-12: n=8). After cytotrophoblast isolation,
the invasive and proliferative phenotypes were immune-separated by an alpha(6)
integrin antibody. Both proliferative and invasive cytotrophoblasts were cultured
separately on plastic or Matrigel for 24 h. ET-1 release into the culture medium
of both cytotrophoblast subtypes was measured by radioimmunoassay. ET(A) and
ET(B) mRNA expression was measured by RT-PCR, and the ET-1 effect on
cytotrophoblast proliferation and invasion was determined using proliferation and
invasion assays, respectively. ET-1 release increased from early to late first
trimester of pregnancy in both proliferative (1.8-4.5 fold) and invasive
cytotrophoblasts (9.3-28 fold), especially when cultured on Matrigel. This was
paralleled by less ET(B) mRNA on invasive cytotrophoblasts independent of the
time period in first trimester, whereas ET(A) expression was similar on
proliferative an invasive cytotrophoblasts. Proliferation and invasion of
cytotrophoblasts under control conditions decreased from early to late first
trimester. ET-1 stimulated both processes at both periods with the most
pronounced effect (7-fold) on invasion in late first trimester. The ET-1/ET
receptor system changes between weeks 6-9 and 10-12 in pregnancy. Our data
suggest an autocrine and endocrine ET-1 effect, which is stronger in late than in
early first trimester of pregnancy paralleled by different stimulatory effects on
trophoblast invasion and proliferation. In general, this suggests time as an
additional effector of the critical processes governing placental development in
the first trimester of human pregnancy.
PMID- 29947545
TI - Antibodies targeting human endothelin-1 receptors reveal different conformational
states in cancer cells.
AB - The endothelin axis (endothelins and their receptors) is strongly involved in
physiological and pathological processes. ET-1 plays a crucial role in particular
in tumor diseases. Endothelin-1 receptors (ET(A) and ET(B)) are deregulated and
overexpressed in several tumors such as melanoma and glioma. We studied the
binding of 24 monoclonal antibodies directed against human ET(B) receptors
(hET(B)) to different melanoma cell lines. Few of these mAbs bound to all the
melanoma cell lines. One of them, rendomab B49, bound to ET(B) receptors
expressed at the surface of human glioma stem cells. More recently, we produced
new antibodies directed against human ET(A) receptor (hET(A)). Several antibodies
have been isolated and have been screened on different tumoral cells lines. As
for the mAbs directed against the hET(B) receptor only some of new antibodies
directed against ET(A) receptor are capable to bind the human tumoral cell lines.
Rendomab A63 directed against hET(A) is one of them. We report the specificity
and binding properties of these mAbs and consider their potential use in
diagnosis by an in vivo imaging approach.
PMID- 29947547
TI - Corrigendum.
PMID- 29947546
TI - New therapies for acute myocardial infarction: current state of research and
future promise.
AB - Progress has been made into research on new therapies, mechanical and
pharmacological approaches and repair/regenerative cellular therapy to treat
irreversible cardiovascular pathologies, such as acute myocardial infarction.
Research into cellular therapies is exploring the use of new cellular types.
Although the therapeutic effects of cell therapy remain modest, results from
clinical trials are encouraging. To expand this improvement, advances are being
made that involve the paracrine function of stem cells, the use of growth
factors, miRNA and new biomaterials. In the near future, these therapies should
become part of routine clinical practice.
PMID- 29947548
TI - Latent Profile Analyses of Depressive Symptoms in Younger and Older Oncology
Patients.
AB - The aging of America will include a significant increase in the number of older
patients with cancer, many of whom will experience significant depressive
symptoms. Although geriatric depression is a well-studied construct, its symptom
presentation in the context of cancer is less clear. Latent profile analysis was
conducted on depressive symptoms in younger (40-64 years) and older (>=65 years)
patients with cancer ( N = 636). The sample was clinically heterogeneous (i.e.,
included all stages, dominated by advanced stage disease). Participants completed
questionnaires including the Center for Epidemiological Studies Depression Scale,
which was used for the latent profile analysis. A four-class pattern was
supported for each age group. However, the four-class pattern was significantly
different between the younger and older groups in terms of the item means within
each corresponding latent class; differences were primarily driven by severity
such that across classes, older adults endorsed milder symptoms. An unexpected
measurement issue was uncovered regarding reverse-coded items, suggesting that
they may generate unreliable scores on the Center for Epidemiological Studies
Depression Scale for a significant subset of patients. The results indicate that
cancer clinicians can expect to see depressive symptoms along a continuum of
severity for patients of any age, with less severe symptoms among older patients.
PMID- 29947549
TI - Development and validation of a functional cell-based neutralizing antibody assay
for ipilimumab.
AB - Ipilimumab is the first US FDA-approved immune checkpoint-blocking antibody drug
to harness the patient's own immune cells. One of the postmarketing requirements
is to develop a cell-based neutralizing antibody assay. Here, we share some of
the most challenging aspects encountered during the assay development: new cell
line construction; an unexpected inhibition of T-cell activation by low
concentrations of ipilimumab; and two issues caused by sample pretreatment with
acid dissociation to overcome drug interference: instability of neutralizing
antibody positive control at low pH, and incompatibility of commonly used acid
dissociation buffers in the cell assay. After troubleshooting and optimization,
we successfully validated the assay and used the assay to test clinical samples
to date.
PMID- 29947550
TI - Blood pressure and heart rate variability are linked with hyperphosphatemia in
chronic kidney disease patients.
AB - Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and is
associated with cardiovascular disease (CVD), which has contributed to an
increase in mortality of CKD patients. The onset of CVD often varies by time-of
day. Acute myocardial infarction or ventricular arrhythmia occurs most frequently
during early morning. Blood pressure (BP) and heart rate circadian rhythms
account for the diurnal variations in CVD. Preservation of normal circadian time
structure from the cardiomyocyte level to the whole organ system is essential for
cardiovascular health and CVD prevention. Independent risk factors, such as
reduced heart rate variability (HRV) and increased BP variability (BPV), are
particularly prevalent in patients with CKD. Analysis of HRV is an important
clinical tool for characterizing cardiac autonomic status, and reduced HRV has
prognostic significance for various types of CVD. Circadian BP rhythms are
classified as extreme dipper, dipper, non-dipper or riser. It has been reported
that nocturnal riser BP pattern contributes to cardiovascular threats. Previous
studies have indicated that the circadian rhythm of serum phosphate in CKD
patients is consistent with the general population, with the highest diurnal
value observed in the early morning hours, followed by a progressive decrease to
the lowest value of the day, which occurs around 11:00 am. Rhythm abnormalities
have become the main therapeutic target for treating CVD in CKD patients. It has
been reported that high levels of serum phosphate are associated with reduced HRV
and increased BPV in CKD patients. However, the mechanisms related to
interactions between hyperphosphatemia, HRV and BPV have not been fully
elucidated. This review focuses on the evidence and discusses the potential
mechanisms related to the effects of hyperphosphatemia on HRV and BPV.
PMID- 29947552
TI - Blockade of prelimbic glutamate receptor reduces the reinforcing effect of
morphine.
AB - The prelimbic cortex (PrL) as a part of the medial prefrontal cortex (mPFC) plays
a crucial role in drug addiction. Previous studies have shown that glutamatergic
transmission through the NMDA and AMPA receptors plays an important role in
morphine rewarding properties. In this study, we evaluated the effect of
glutamate receptors blockade within the PrL on morphine self-administration. Male
Wistar rats were randomly selected and divided into 7 groups. Trained rats were
placed in self-administration apparatus, where they pressed an active lever for
receiving morphine (5 mg/mL) in test groups and saline in saline group during 11
consecutive days for 2 h per session. The effects of intra-prelimbic AMPA
receptor antagonist (CNQX; 0.5 and 2.5 MUg/0.5 MUL) and the NMDA antagonist (AP5;
0.1 and 1 MUg/0.5 MUL) on self-administration were tested. Our results
demonstrated that intra-prelimbic injection of different doses of CNQX and AP5,
and co-administration of these 2 drugs before self-administration significantly
decreased active lever pressing compared with morphine group (p < 0.001). Also,
the number of self-infusion significantly decreased in test groups compared with
morphine group (p < 0.001). These findings suggest that a reduction in PrL
glutamatergic output can modulate morphine reinforcement.
PMID- 29947553
TI - Life Course Transitions and Changes in Alcohol Consumption Among Older Irish
Adults: Results From The Irish Longitudinal Study on Ageing (TILDA).
AB - OBJECTIVE: The objective of this study was to determine whether trajectories of
older adults' alcohol consumption are influenced by the following life course
transitions, relationship status, employment status, and self-rated health.
METHOD: Volume and frequency of drinking were harmonized across first three waves
of The Irish Longitudinal Study on Ageing (TILDA; N = 4,295). Multilevel
regression models were used to model frequency, average weekly consumption, and
heavy episodic drinking. RESULTS: Men and women drank more frequently over time,
with frequency decreasing with age for women. Average weekly consumption
decreased over time and with increasing age. Transitions in self-rated health,
particularly those reflecting poorer health, were associated with lower frequency
and weekly consumption. Heavy episodic drinking decreased with age. Men who were
retired across all waves were more likely to engage in heavy episodic drinking at
baseline. DISCUSSION: Despite the decline in average weekly consumption and heavy
episodic drinking, the observed quantities consumed and the increase in frequency
of consumption suggest that older Irish adults remain vulnerable to alcohol
related harms.
PMID- 29947554
TI - Mothers' Perspectives on Managing the Developmental Delay of a Child With
Considerations for Contextual Influences and Maternal Functioning.
AB - Developmental delay in very young children is trending upward. Maternal
depressive symptoms are known to negatively impact child development and may also
impact family management of the child's condition. Research on family management
guided this second phase of a sequential mixed methods study. The purpose of this
study was to explore mothers' perceptions of family management of their
children's developmental delays. Mothers of very young children who received
early intervention services were interviewed. A team-based content analysis
approach revealed key findings: (a) views of the child that were not holistic,
(b) condition management ability was informed by what the mother thought her
child needed, (c) views of condition impact were related to adapting to possible
child outcomes and experiences of isolation, and (d) parental/caregiver mutuality
was impaired by conflict. Understanding perceptions of family management and
influence of depressive symptoms in this context is essential to extend
assessment and intervention.
PMID- 29947555
TI - Clinical characteristics and treatment outcomes among respiratory syncytial virus
(RSV)-infected hematologic malignancy and hematopoietic stem cell transplant
recipients receiving palivizumab.
AB - Palivizumab has been used to treat respiratory syncytial virus (RSV)-infected
hematologic malignancy patients at our institution based on limited published
data. We conducted this retrospective study to evaluate clinical outcomes and
mortality rates of RSV-infected hematologic malignancy patients from 2007 to
2016. A total of 67 patients (19 received palivizumab and 47 received supportive
care) were identified. Palivizumab-treated patients had a significantly higher
proportion of underlying ischemic heart disease, graft-versus-host-disease,
hypogammaglobulinemia, and concomitant pulmonary infections. There were no
significant differences in mortality rates or readmission rates between the two
groups. The estimated odds ratio for death in patients receiving palivizumab
after adjusting for propensity scores and covariates were 0.12 ([0.01, 1.32], p =
.08) and 0.09 ([0.01, 1.03], p = .05) respectively. After adjustment for factors
associated with severity of illness, there was no difference in mortality among
patients treated with palivizumab.
PMID- 29947556
TI - Why some people do well and others don't. The role of sense of coherence in
disease adaptation.
PMID- 29947558
TI - Corrigendum.
PMID- 29947557
TI - Effective prevention of secondary pneumococcal infection following influenza
virus infection.
PMID- 29947559
TI - Reliability and Validity of the Checklist for Function-Focused Care in Service
Plans.
AB - The purpose of this study was to test the reliability and validity of the
Checklist for Function-Focused Care in Service Plans. Function-focused care is a
care approach that optimizes function and physical activity during all care
interactions. This study used baseline data from the first cohort of the study
titled Dissemination and Implementation of Function-Focused Care for Assisted
Living Using the Evidence Integration Triangle (FFC-AL-EIT). A total of 242
participants were recruited from 26 assisted living facilities. The majority of
participants were White, female, and unmarried. There was support for internal
consistency with an alpha coefficient of .96, interrater reliability with a
correlation of .80, construct validity based on Rasch analysis and INFIT
statistics ranging from 0.69 to 1.29, and a significant association with function
focused care activities. Although there is some support for reliability and
validity of the measure, modifications are recommended to add more challenging
items.
PMID- 29947560
TI - Mitochondrial disease: learning from Charlie's lesson, trying to cure, trying
much more to care.
PMID- 29947561
TI - A cohort study examining the factors influencing changes in physical activity
levels following an acute coronary syndrome event.
AB - BACKGROUND: Low physical activity has long been identified as a risk factor for
coronary heart disease. AIMS: The aim of this study was to determine the factors
that influence changes in the physical activity of patients following an acute
coronary syndrome event. METHODS: The prospective, inferential cohort design
recruited patients admitted to hospital following an acute coronary syndrome
event across five research sites. Physical activity was assessed using the short
form international physical activity questionnaire. RESULTS: Data were collected
at baseline and 3 months on 380 patients. The sample profile was: 21% women; body
mass index 28 +/- 4.6; unstable angina 36%; ST-segment elevation myocardial
infarction 25%; non-ST-segment elevation myocardial infarction 39% and a mean age
of 63 +/- 11.8. There was a significant improvement in physical activity at 3
months ( n=380, t=-3.704, P<=0.001). All regression models, baseline, 3 months
and change in physical activity were significant ( p<=0.001). Low physical
activity was associated with: at baseline not having health insurance, older age
and depression; at 3 months not having health insurance, not in employment and
low baseline physical activity; and improvement in physical activity was
associated with low physical activity at baseline and not being in employment.
CONCLUSIONS: While physical activity improved significantly, 45% did not reach
guideline recommendation levels at 3 months post-event. Physical activity change
was little influenced by sociodemographic, clinical, psychological and
behavioural factors, suggesting the need to look elsewhere such as behavioural
change and improved processes across the care divide to improve physical activity
in this at-risk population.
PMID- 29947562
TI - Can Social Support Overcome the Individual and Structural Challenges of Being a
Sex Offender? Assessing the Social Support-Recidivism Link.
AB - Social support is important for individual's successful reentry; however, little
is known about how it operates or is influenced by individual and structural
factors. Understanding how social support matters for individuals convicted of a
sex offense is especially important as they may have a different reentry
experience due to the nature of their crime and post-conviction restrictions.
This study examines the nature and effects of instrumental and expressive social
support from family, friends, intimate partners, and parole officers on
recidivism for a sample of men convicted of sex offenses using mixed methods.
Results show that family, friend, and intimate partner support had no effects on
recidivism, however participants reporting a positive relationship with their
parole officer were more likely to return to prison. Qualitative analysis of in
depth interviews sheds light on how the nature of these relationships might
explain the social support-recidivism link in a high stakes population.
PMID- 29947564
TI - Primary Care Providers' Attitudes Related to LGBTQ People: A Narrative Literature
Review.
AB - The purpose of this article is to review the current literature describing
primary care providers' (PCPs) attitudes related to lesbian, gay, bisexual,
transgender, and queer/questioning (LGBTQ) people. LGBTQ individuals experience
significant health disparities, and these inequities may be better understood via
an ecological systems framework. PCPs' actual or perceived discriminatory
attitudes can lead to suboptimal treatment or health outcomes for LGBTQ people. A
review of the literature from 2005 through January 2017 was completed using the
Cumulative Index for Nursing and Allied Health Literature and PubMed (Medline)
databases. The purpose, sample, measure(s), design, findings, strengths, and
weaknesses of each study were examined; and findings were synthesized,
summarized, and critically appraised. Eight articles were eligible for review.
There was significant heterogeneity in the studies' purposes, research questions,
LGBTQ population(s) of focus, and findings. Many PCPs' attitudes toward LGBTQ
people were positive, but a minority of each studies' participants had negative
attitudes toward LGBTQ people. Stigma and health care barriers negatively affect
LGBTQ health. Interventions must address LGBTQ health disparities at the
individual, mesosytem, exosystem, and macrosystem levels. Research, education,
and practice strategies all must be integrated across socioecological levels as
components of a population-based approach to eliminate health disparities for
LGBTQ persons.
PMID- 29947563
TI - Disclosure of Same-Sex Behaviors to Health-care Providers and Uptake of HIV
Testing for Men Who Have Sex With Men: A Systematic Review.
AB - To promote HIV-testing and offer optimal care for men who have sex with men
(MSM), health-care providers (HCPs) must first be aware of their patients' sexual
behaviors. Otherwise, HCPs may overlook MSM's risks for HIV infection and their
special health-care needs. For MSM, reporting their same-sex behaviors to HCPs
(disclosure to HCPs) may promote their linkage to HIV prevention and treatment
cascade and improve their health outcomes. No literature review has been
conducted to examine the relationship between disclosure to HCPs and uptake of
HIV-testing among MSM. The current study reviewed and synthesized findings from
29 empirical studies published in English by 2016. We summarized the rates of
MSM's disclosure to HCPs, investigated the association between disclosure and HIV
testing among MSM, identified potential facilitators and barriers for disclosure,
and discussed the implications of our findings in research and clinical
practices. The disclosure rates varied across subgroups and study settings,
ranging from 16% to 90% with a median of 61%. Disclosure to HCPs was positively
associated with uptake of HIV-testing. African American MSM were less likely to
disclose to HCPs. MSM who lived in urban settings with higher education
attainment and higher income were more likely to disclose. MSM tended to perceive
younger or gay-friendly doctors as safer targets of disclosure. Clinics with LGBT
friendly signs were viewed as safer contexts for disclosure. Having previous
communications about substance use, sex, and HIV with HCPs could also facilitate
disclosure. The main reasons for nondisclosure included lack of probing from
HCPs, concerns on confidentiality breach and stigma, and perceived irrelevance
with services. Providing appropriate trainings for HCPs and creating gay-friendly
clinical settings can be effective strategies to facilitate disclosures of same
sex behaviors among MSM and meet their specific medical needs. Interventions to
promote disclosure should give priorities to MSM from the most marginalized
subgroups (e.g., MSM in rural areas, MSM of ethnic minorities).
PMID- 29947566
TI - The Association Between Happiness and Self-Rated Physical Health of African
American Men: A Population-Based Cross-Sectional Study.
AB - Happiness and self-rated physical health are included in national surveys to
assess health perceptions and subjective well-being among individuals. Studies
have reported that happiness impacts physical health; however, little is known
about the association between happiness and self-rated physical health among
African American men (AAM). The objective of this study is to examine this
relationship. Participants were 1,263 AAM aged 18+ years from the National Survey
of American Life who rated their happiness and physical health. Interviews were
conducted between 2001 and 2003. Self-rated physical health was defined as how
individuals rated their own physical health and happiness as how individuals
perceived their subjective well-being. Three multivariate logistic regression
models were used to examine the relationships between happiness and self-rated
physical health. It was observed that AAM who were happy were more likely to be
married, to be employed, and earn more than $30,000 annually compared to AAM who
were not happy. AAM who were happy were less likely to rate their physical health
as fair/poor relative to AAM who were not happy. When controlling for demographic
and socioeconomic factors, AAM who reported being happy had lower odds of rating
their physical health as fair/poor compared to AAM who reported not being happy.
Findings suggest that AAM who are happy report better physical health than those
who report not being happy. Public health promotion strategies focusing on AAM
should consider happiness as a promising influence that may positively impact
physical health.
PMID- 29947567
TI - Two-year progression analysis of RPE65 autosomal dominant retinitis pigmentosa.
AB - BACKGROUND: The RPE65 gene was recently described to cause autosomal dominant
retinitis pigmentosa (adRP), presenting with a phenotype resembling
choroideremia. This study presents the 2-year progression of RPE65 adRP in a
patient. METHODS: This is an observational case report of one patient. The
patient received a full ophthalmic examination during both visits, including
diagnostic imaging such as spectral domain optical coherence tomography (SD-OCT),
OCT-angiography (OCT-A), short-wave fundus autofluorescence (FAF), and fundus
photography. Genetic characterization was obtained by DNA sequencing from
peripheral blood lymphocytes obtained during the first visit. RESULTS: RPE65 adRP
phenocopied choroideremia at the initial fundoscopy. Upon the patient's return to
our clinic 2 years later, DNA sequencing revealed a heterozygous mutation in the
RPE65 gene. Diagnostic imaging by SD-OCT and FAF suggested disease progression.
In conjunction with clinical examination and imaging, the diagnosis was revised
to adRP caused by RPE65. CONCLUSION: adRP due to a mutation in the gene encoding
RPE65 phenocopied choroideremia. Based on our analysis of the 2-year disease
progression in this patient, RPE65 adRP is mild and has a slow rate of disease
progression.
PMID- 29947565
TI - The Role of Felt or Enacted Criticism in Parents' Decision Making in Differing
Contexts and Communities: Toward a Formal Grounded Theory.
AB - Felt or enacted criticism was identified as a significant influence on White
British parents' decision making during acute childhood illness in a substantive
grounded theory "Containing acute childhood illness within family life." These
parents sought to avoid further criticism, sometimes leading to delayed
consultation. Using Glaserian grounded theory principles, we conducted a
secondary analysis of data from three studies, to establish the transferability
and modifiability of the original theory to other settings and communities in
Ireland and England. Felt or enacted criticism was found to operate across the
childhood age range, social groups, and settings. Parent's strategies to avoid
criticism reduced contacts with health professionals, access to support and, more
worryingly, communication about their child's health. These findings demonstrate
the wider applicability, or "work" in Glaser's terms, of the concept in the
English speaking Western world. Findings indicate the need for nurses to identify
and mitigate sources of criticism.
PMID- 29947568
TI - The association of matrix metalloproteinases polymorphisms and interleukins in
advanced age-related macular degeneration.
AB - PURPOSE: To assess the impact of matrix metalloproteinase (MMP)1-1607 1G/2G
(rs1799750), MMP7-181 A/G (rs11568818) single-nucleotide polymorphism and
systemic cytokins interleukin-1 beta (IL-1beta), IL-6 levels on the development
of exudative age-related macular degeneration (eAMD) Methodology: The study group
comprised 282 patients with eAMD, and the control group enrolled 379 randomly
selected persons. The genotyping of MMP1-1607 (rs1799750) and MMP7-181
(rs11568818) was performed by using the polymerase chain reaction-based
restriction fragment length polymorphism method. To determine IL-1beta and IL-6
serum levels, the immunoenzymatic method with monoclonal antibodies coated plates
was performed. RESULTS: MMP1 rs1799750 1G/2G genotype was more frequently found
in the development of eAMD. It was associated with a 4.3-fold increased risk for
eAMD under the codominant model and a 4.9-fold increased risk for eAMD under the
overdominant model. The effect was more pronounced at the age of less than 65
years. IL-1beta concentration was significantly higher for MMP1 rs1799750 1G/1G
genotype and MMP7 rs11568818 A/G genotype in eAMD patients compared with control
group subjects. CONCLUSIONS: MMP1 rs1799750 1G/2G genotype was found to play a
significant role in the development of eAMD at the age of less than 65 years. IL
1beta concentration was significantly higher in eAMD patients for MMP1 rs1799750
1G/1G genotype and MMP7 rs11568818 A/G genotype compared with control group
subjects.
PMID- 29947569
TI - A novel MIP mutation in a Chinese family with congenital cataract.
AB - PURPOSE: To identify the disease-causing gene of a four-generation Chinese family
with congenital cataract. METHODS: To screen the disease-causing gene of the
family, six disease genes of congenital cataract are screened by direct DNA
sequencing, the cDNA of wild-type (WT) MIP gene, and P191R mutant MIP gene (MT)
were constructed into pEGFP-C1 vector and pGH19 vector. The recombinant plasmids
of pEGFP-C1, WT, and mutant MIP were transfected into Hela cell to check the
localization and HEK293T cells to detect expression level of protein. The cRNA of
WT and MT MIP gene were injected into Xenopus oocytes to measure the swelling
rate. RESULTS: A novel missense mutation c.572C>G(p.P191R)at exon 3 of the MIP
gene was identified and co-segregated with disease in the Chinese family. The
same amount of pEGFP-WT MIP and pEGFP- P191R MIP plasmids were transfected in
Hela cells. Confocal microscopy imaging showed that WT MIP protein predominantly
localized on the plasma membrane, the mutant protein was rich in the cytoplasm in
Hela cells. Western blot results show that the expression level of P191R mutant
MIP was significantly lower than WT MIPincell membrane enriched lysates in
HEK293T cells. Xenopus oocytes swelling assay showed that the P191R mutation
reduces the swelling rate of Xenopus oocytes. CONCLUSIONS: The novel missense
mutation c.572C>G(p.P191R)at exon 3 of the MIP gene was identified in a Chinese
family of congenital cataract. The mutation affects the traffic of MIP protein in
the cells and reduces the expression level of MIP protein in the cell membrane.
The mutation of MIP gene reduces the swelling ratio of Xenopus oocytes.
PMID- 29947570
TI - Identification and characterization of the VAX2 p.Leu139Arg variant: possible
involvement of VAX2 in cone dystrophy.
AB - OBJECTIVE: This study was undertaken with the objective to investigate the
potential involvement of VAX2 in retinal degeneration. METHODS: A cohort of
macular and cone dystrophy patients (n = 70) was screened for variant
identification. Polymerase chain reaction (PCR) products were purified using
ExoSAP-IT. Direct sequencing of PCR products was performed using BigDye 3.1 on
the ABI 3730 DNA Analyzer and analyzed using DNASTAR software tool. Search for
known variant was performed using the following platforms: 1000 Genomes Project,
Ensembl, UCSC, ExAc, and dbSNP. The VAX2 mutants were generated using the
GeneArt(r) Site-Directed Mutagenesis kit. In vitro analysis was performed in
hTERTRPE-1 (RPE-1) cell line. Cells were photographed using a Zeiss AXIOVERT S100
microscope. Images were analyzed using Photoshop CS4 software. RESULTS: Here, we
report the identification of a heterozygous non-synonymous variant (c.416T>G;
p.Leu139Arg) in one cone dystrophy proband. Functional characterization of this
variant in vitro revealed an aberrant phenotype seen as protein mislocalization
to cytoplasm/nucleus and aggregates undergoing degradation or forming aggresomes.
The cellular phenotype suggests protein loss-of-function. Analysis of the VAX2
p.Leu139Met, a variant present in the normal population, showed a phenotype
similar to the wild-type, further supporting the hypothesis for the Leucine 139
to Arginine change to be damaging. CONCLUSIONS: This study raises the interesting
possibility for evaluating VAX2 as a candidate gene for cone dystrophy.
PMID- 29947571
TI - Best Practices for Testing the Predictive Validity of Ideal Partner Preference
Matching.
AB - Many psychological hypotheses require testing whether the similarity between two
variables predicts important outcomes. For example, the ideal standards model
posits that the match between (A) a participant's ideal partner preferences, and
(B) the traits of a current/potential partner, predicts (C) evaluative outcomes
(e.g., the decision to date someone, relationship satisfaction, breakup); tests
of the predictive validity of ideal-matching require A * B -> C analytic
strategies. However, recent articles have incorrectly suggested that documenting
a positive samplewide correlation between a participant's ideals and a current
partner's traits (an A-B correlation) implies that participants pursued,
selected, or desired partners with traits that matched their ideals. There are at
least six alternative explanations for the emergence of a samplewide A-B
correlation; A-B correlations do not provide evidence that ideals guide the
selection/evaluation of specific partners. We review appropriately rigorous A * B
-> C tests that can aid scholars in identifying the circumstances in which ideal
matching exhibits predictive validity.
PMID- 29947572
TI - A single dose of cocaine enhances prospective memory performance.
AB - BACKGROUND: Prospective memory is the ability to recall intended actions or
events at the right time or in the right context. While cannabis is known to
impair prospective memory, the acute effect of cocaine is unknown. In addition,
it is not clear whether changes in prospective memory represent specific
alterations in memory processing or result from more general effects on cognition
that spread across multiple domains such as arousal and attention. AIMS: The main
objective of the study was, therefore, to determine whether drug-induced changes
in prospective memory are memory specific or associated with more general drug
induced changes in attention and arousal. METHODS: A placebo-controlled, three
way, cross-over study including 15 regular poly-drug users was set up to test the
influence of oral cocaine (300 mg) and vaporised cannabis (300+150 'booster'
ug/kg bodyweight) on an event-based prospective memory task. Attentional
performance was assessed using a divided attention task and subjective arousal
was assessed with the Profile of Mood States questionnaire. RESULTS: Results
showed that cocaine enhanced prospective memory, attention and arousal. Mean
performance of prospective memory and attention, as well as levels of arousal
were lowest during treatment with cannabis as compared with placebo and cocaine
as evinced by a significantly increased trend across treatment conditions.
Prospective memory performance was only weakly positively associated to measures
of attention and arousal. CONCLUSION: Together, these results indicate that
cocaine enhancement of prospective memory performance cannot be fully explained
by parallel changes in arousal and attention levels, and is likely to represent a
direct change in the neural network underlying prospective memory.
PMID- 29947573
TI - Extending human IgG half-life using structure-guided design.
AB - Engineering of antibodies for improved pharmacokinetics through enhanced binding
to the neonatal Fc receptor (FcRn) has been demonstrated in transgenic mice, non
human primates and humans. Traditionally, such approaches have largely relied on
random mutagenesis and display formats, which fail to address related critical
attributes of the antibody, such as effector functions or biophysical stability.
We have developed a structure- and network-based framework to interrogate the
engagement of IgG with multiple Fc receptors (FcRn, C1q, TRIM21, FcgammaRI,
FcgammaRIIa/b, FcgammaRIIIa) simultaneously. Using this framework, we identified
features that govern Fc-FcRn interactions and identified multiple distinct
pathways for enhancing FcRn binding in a pH-specific manner. Network analysis
provided a novel lens to study the allosteric impact of half-life-enhancing Fc
mutations on FcgammaR engagement, which occurs distal to the FcRn binding site.
Applying these principles, we engineered a panel of unique Fc variants that
enhance FcRn binding while maintaining robust biophysical properties and wild
type-like binding to activating receptors. An antibody harboring representative
Fc designs demonstrates a half-life improvement of > 9 fold in transgenic mice
and > 3.5 fold in cynomolgus monkeys, and maintains robust effector functions
such as antibody-dependent cell-mediated cytotoxicity and complement-dependent
cytotoxicity.
PMID- 29947574
TI - Vaccine Hesitancy in Pediatric Primary Care Practices.
AB - Understanding how pediatric practices handle parental vaccine hesitancy is
important as it impacts the efficiency and effectiveness of pediatric practices.
In total, 21 semi-structured interviews with pediatric practice staff within a
primary care network were conducted between May 2012 and March 2013. Thematic
analysis focused on the barriers and challenges of vaccine hesitancy and
strategies to reduce the burden at the practice level. Barriers and challenges of
vaccine hesitancy included time constraints, administrative challenges, financial
challenges and strained patient-provider relationships. Strategies to minimize
the burden of vaccine hesitancy included training for vaccine counseling,
screening for vaccine hesitancy prior to immunization visits, tailored vaccine
counseling, and primary care provider visits for follow-up immunization.
Pediatric practices reported many challenges when caring for vaccine-hesitant
families. Multiple strategies were identified to reduce the burden of vaccine
hesitancy, which future studies should explore to determine how effective they
are in increasing vaccine acceptance in pediatric practices.
PMID- 29947575
TI - Energy drinks, caffeine, junk food, breakfast, depression and academic attainment
of secondary school students.
AB - BACKGROUND: Energy drinks are widely consumed, and concerns have been raised
about possible negative outcomes. AIMS: The aim of the present research was to
examine associations between consumption of energy drinks, caffeine and junk
food, and academic attainment in a sample of UK secondary school students.
METHODS: A total of 3071 students agreed to participate in the study; 2677
completed the survey on one occasion (52.4% female, 47.6% male; approximately 20%
of the sample from each school year) and 1660 (49.6% female, 50.4% male)
completed the survey a second time, approximately six months later. The academic
attainment measure was based on Key Stage 3 and Key Stage 4 grades for Maths and
English. RESULTS: In the cross-sectional analyses, logistic regressions showed
that consumption of energy drinks was associated with a greater likelihood of
being in the low academic achievement group. This was not found for other sources
of caffeine. The effect of energy drinks was still significant when demographic,
academic and health/lifestyle variables were covaried. However, inclusion of an
unhealthy diet variable (junk food) removed the significant effect of energy
drinks. Similar observations were made in the longitudinal study, with the poorer
attainment of those who consumed energy drinks reflecting breakfast omission and
depression. DISCUSSION: The present findings indicate that consumption of energy
drinks is associated with an increased likelihood of poor academic attainment
that reflects energy drink consumption being part of an unhealthy diet or being
associated with skipping breakfast rather than a more specific effect, such as
being a source of caffeine. Although the current study extends previous research
by utilising a longitudinal design, intervention studies are now required to
better answer questions relating to causality and direction of effect.
PMID- 29947576
TI - A retrospective case study of sunitinib treatment in three patients with Von
Hippel-Lindau disease.
AB - Von Hippel-Landau (VHL) disease is characterized by malignant and benign tumors
in multiple organs. Sunitinib, a tyrosine kinase inhibitor, has been clinically
available for treating sporadic patients with recurrent or unresectable and
metastatic clear renal cell carcinomas (cRCCs) and metastatic lesions of the
lung, but its effect on VHL disease-associated tumors remains poorly understood.
This retrospective case series examined the effect of sunitinib on RCC,
hemangioblastomas, pheochromocytomas, and pancreatic neuroendocrine tumors in
patients with confirmed VHL. Of note, three patients with VHL disease who were
treated with sunitinib were identified from a review of their medical records.
The efficacy of sunitinib was evaluated by comparing computed tomography (CT) or
magnetic resonance imaging (MRI) scans conducted before and after treatment.
Adverse side effects associated with sunitinib were assessed and recorded. All
three patients with VHL disease exhibited clinical improvement after treatment
with sunitinib. Patient 1 exhibited a decrease in the size of both their
pheochromocytoma and RCC after 19 months of sunitinib treatment. RCCs in Patients
2 and 3 exhibited stable response to sunitinib for approximately 1 and 6 years,
respectively. All the patients reported tolerable side effects. Therefore
sunitinib treatment was associated with either partial response or stable control
of VHL-related RCCs, pheochromocytomas and pancreatic neuroendocrine tumor (NET)
with acceptable side effects. Further evaluation of sunitinib in patients with
VHL disease in larger prospective studies is warranted.
PMID- 29947577
TI - Over-expression of StZFP2 in Solanum tuberosum L. var. Kennebec (potato) inhibits
growth of Tobacco Hornworm larvae (THW, Manduca sexta L.).
AB - Tobacco hornworm (Manduca sexta, THW) is a voracious pest of tomato and potato.
StZFP2 is a Q-type C2H2 zinc finger transcription factor (TF) that is induced
upon wounding and infestation. Previous work has shown that Q-type C2H2 TFs are
involved in stress responses and when over expressed, can enhance protection
against drought, salinity or pathogen infection. Twelve transgenic lines (S1-S12)
were tested that over-express StZFP2. Feeding S6 or S8 to THW significantly
lowered larval weight (21-37%) as well as increased expression of StPIN2 in
comparison to untransformed Kennebec. The increase in StPIN2, a classic marker
for insect defense in potato, is consistent with the decreases in larval weight
gain.
PMID- 29947578
TI - Health Literacy Deficits Found Among Educated, Insured University Employees.
AB - Evidence has consistently shown that low/limited health literacy (HL) is
associated with negative health consequences and higher costs for individuals and
society. To generate internal data for employee training and health/wellness
programming, an HL assessment of 120 university employees was conducted using the
Newest Vital Sign (NVS), a valid and reliable clinical screening tool that asks
individuals to interpret a nutrition label. Sociodemographic data were collected
and time to administer the NVS tool was also measured. Even in this employed,
well-educated sample (mean years of formal education was 16.6 years), 17% had
scores indicating limited or possibly limited HL. Findings have implications for
occupational training and health providers and programs. Even a well-educated
workforce benefits from addressing HL challenges or situational issues with
universal strategies. This project supports initiatives to assist employees
better navigate, understand, and use health information and services to improve
their health.
PMID- 29947580
TI - Who Is Most Likely to Wear Rose-Colored Glasses? How Regulatory Mode Moderates
Self-Flattery.
AB - In general, people prefer to view themselves positively. But some individuals are
more prone to self-flattery than others, that is, holding an unjustifiably high
opinion of oneself. Applying regulatory mode theory, we identify motivational
factors that predict which individuals are and are not prone to self-flattery. In
four studies, using both chronic (Studies 1-3) and experimental (Study 4)
conditions, we found that those with high locomotion concerns about effecting
change (control) are more inclined to flatter themselves, whereas those with high
assessment concerns about making the right choices (truth) are less inclined to
flatter themselves. The relation between stronger locomotion and greater self
flattery, and stronger assessment and lesser self-flattery, was mediated by
locomotors' low self-criticism and assessors' high self-criticism. These results
shed light on how locomotion and assessment differ in the motivation to flatter
oneself.
PMID- 29947579
TI - Continence technologies whitepaper: Informing new engineering science research.
AB - Advances in healthcare technology for continence have historically been limited
compared to other areas of medicine, reflecting the complexities of the condition
and social stigma which act as a barrier to participation. This whitepaper has
been developed to inspire and direct the engineering science community towards
research opportunities that exist for continence technologies that address unmet
needs in diagnosis, treatment and long-term management. Our aim is to pinpoint
key challenges and highlight related research opportunities for novel
technological advances. To do so, we draw on experience and expertise from
academics, clinicians, patients and patient groups linked to continence
healthcare. This is presented in four areas of consideration: the clinical
pathway, patient perspective, research challenges and effective innovation. In
each we introduce seminal research, background information and demonstrative case
studies, before discussing their relevance to engineering science researchers who
are interested in approaching this overlooked but vital area of healthcare.
PMID- 29947581
TI - Automated Surgical Approach Planning for Complex Skull Base Targets: Development
and Validation of a Cost Function and Semantic At-las.
AB - Successful multidisciplinary treatment of skull base pathology requires precise
preoperative planning. Current surgical approach (pathway) selection for these
complex procedures depends on an individual surgeon's experiences and background
training. Because of anatomical variation in both normal tissue and pathology
(eg, tumor), a successful surgical pathway used on one patient is not necessarily
the best approach on another patient. The question is how to define and obtain
optimized patient-specific surgical approach pathways? In this article, we
demonstrate that the surgeon's knowledge and decision making in preoperative
planning can be modeled by a multiobjective cost function in a retrospective
analysis of actual complex skull base cases. Two different approaches- weighted
sum approach and Pareto optimality-were used with a defined cost function to
derive optimized surgical pathways based on preoperative computed tomography (CT)
scans and manually designated pathology. With the first method, surgeon's
preferences were input as a set of weights for each objective before the search.
In the second approach, the surgeon's preferences were used to select a surgical
pathway from the computed Pareto optimal set. Using preoperative CT and magnetic
resonance imaging, the patient-specific surgical pathways derived by these
methods were similar (85% agreement) to the actual approaches performed on
patients. In one case where the actual surgical approach was different, revision
surgery was required and was performed utilizing the computationally derived
approach pathway.
PMID- 29947582
TI - "Home Is Where My Couch Is": The Role of Possessions in the Process of Moving and
Adjusting to Continuing Care Retirement Communities.
AB - We examined the role of possessions in the process of moving and adjusting to
continuing care retirement communities (CCRCs). Totally, 59 CCRC residents in 12
CCRCs were interviewed. We categorized three main types of residents: "I want it
all," "I want it that way," and "I want to break free." Each type experienced
differently the role that objects play in (a) the reasons for moving, (b)
choosing a CCRC and a specific apartment, (c) organizing one's belongings in
preparation for relocation, and (d) adjusting to the new apartment. Most
residents were attached to their belongings and reported having great difficulty
leaving them behind. Our findings suggest that while older adults should be given
every possible opportunity to make their own choices about their belongings, it
is also necessary to balance between the desire to maintain continuity with their
past, and the limited space of a CCRC apartment.
PMID- 29947583
TI - A scale-development study: Exploration of intensive-care nurses' attitudes
towards futile treatments.
AB - The study was conducted to determine the validity and reliability of the tool
used to assess nurses' attitudes towards futility, and to explore intensive-care
nurses' attitudes towards futility. Principal components analysis revealed that
18item scale was made up of four subdimensions that assess Identifying(beliefs),
Decision-Making, Ethical Principles and Law, and Dilemma and Responsibilities
related to futile treatments. The internal consistency of the scale was in the
acceptable range, with a total Cronbach's alpha value of 0.72. Overall the
results of study suggest that scale can be used as a valid and reliable
assessment tool to assess nurses' attitudes towards futility.
PMID- 29947584
TI - Collective team behaviour of Australian Rules football during phases of match
play.
AB - Using the spatiotemporal characteristics of players, the primary aim of this
study was to determine whether differences in collective team behaviour exist in
Australian Rules football during different phases of match play. The secondary
aim was to determine the extent to which collective team behaviour differed
between competing teams and match half. Data was collected via 10 Hz global
positioning system devices from a professional club during a 2 * 20 min, 15-v-15
match simulation drill. Five spatiotemporal variables from each team (x centroid,
y centroid, length, width, and surface area) were collected and analysed during
offensive, defensive, and contested phases. A multivariate analysis of variance
comparing phase of match play (offensive, defensive, contested), Team (A & B),
and Half (1 & 2) revealed that x-axis centroid and y-axis centroid showed
considerable variation during all phases of match play. Length, width, and
surface area were typically greater during the offensive phase comparative to
defensive and contested phases. Clear differences were observed between teams
with large differences recorded for length, width, and surface area during all
phases of match play. Spatiotemporal variables that describe collective team
behaviour may be used to understand team tactics and styles of play.
PMID- 29947586
TI - Simultaneous and opposing horizontal VOR adaptation in humans suggests
functionally independent neural circuits.
AB - The healthy vestibulo-ocular reflex (VOR) ensures that images remain on the fovea
of the retina during head rotation to maintain stable vision. VOR behavior can be
measured as a summation of linear and nonlinear properties although it is unknown
whether asymmetric VOR adaptation can be performed synchronously in humans. The
purpose of the present study is twofold. First, examine whether the right and
left VOR gains can be synchronously adapted in opposing directions. Second, to
investigate whether the adaptation context transfers between both sides. Three
separate VOR adaptation sessions were randomized such that the VOR was adapted Up
bilaterally, Down-bilaterally, or Mixed (one side up, opposite side down). Ten
healthy subjects completed the study. Subjects were tested while seated upright,
1 meter in front of a wall in complete dark. Each subject made active (self
generated) head impulse rotations for 15 min while viewing a gradually increasing
amount of retinal slip. VOR training demand changed by 10% every 90 s. The VOR
changed significantly for all training conditions. No significant differences in
the magnitude of VOR gain changes between training conditions were found. The
human VOR can be simultaneously driven in opposite directions. The similar
magnitude of VOR gain changes across training conditions suggests functionally
independent VOR circuits for each side of head rotation that mediate simultaneous
and opposing VOR adaptations. NEW & NOTEWORTHY Our results indicate that humans
have the adaptive capacity for concurrent and opposing directions of vestibulo
ocular reflex (VOR) motor learning. Context specificity of VOR adaptation is
dependent on the error signal being unilateral or bilateral, which we illustrate
via a lack of VOR gain transfer using unique adaptive demands.
PMID- 29947585
TI - Slot-like capacity and resource-like coding in a neural model of multiple-item
working memory.
AB - For the past decade, research on the storage limitations of working memory has
been dominated by two fundamentally different hypotheses. On the one hand, the
contents of working memory may be stored in a limited number of "slots," each
with a fixed resolution. On the other hand, any number of items may be stored but
with decreasing resolution. These two hypotheses have been invaluable in
characterizing the computational structure of working memory, but neither
provides a complete account of the available experimental data or speaks to the
neural basis of the limitations it characterizes. To address these shortcomings,
we simulated a multiple-item working memory task with a cortical network model,
the cellular resolution of which allowed us to quantify the coding fidelity of
memoranda as a function of memory load, as measured by the discriminability,
regularity, and reliability of simulated neural spiking. Our simulations account
for a wealth of neural and behavioral data from human and nonhuman primate
studies, and they demonstrate that feedback inhibition lowers both capacity and
coding fidelity. Because the strength of inhibition scales with the number of
items stored by the network, increasing this number progressively lowers fidelity
until capacity is reached. Crucially, the model makes specific, testable
predictions for neural activity on multiple-item working memory tasks. NEW &
NOTEWORTHY Working memory is the ability to keep information in mind and is
fundamental to cognition. It is actively debated whether the storage limitations
of working memory reflect a small number of storage units (slots) or a decrease
in coding resolution as a limited resource is allocated to more items. In a
cortical model, we found that slot-like capacity and resource-like neural coding
resulted from the same mechanism, offering an integrated explanation for storage
limitations.
PMID- 29947587
TI - Extracellular waveforms reveal an axonal origin of spikelets in pyramidal
neurons.
AB - Spikelets are small spike-like membrane depolarizations measured at the soma
whose origin in pyramidal neurons is still unresolved. We investigated the
mechanism of spikelet generation using detailed models of pyramidal neurons. We
simulated extracellular waveforms associated with action potentials and spikelets
and compared these with experimental data obtained by Chorev and Brecht ( J
Neurophysiol 108: 1584-1593, 2012) from hippocampal pyramidal neurons in vivo. We
considered spikelets originating in the axon of a single cell as well as
spikelets generated in two cells coupled with gap junctions. We found that in
both cases the experimental data can be explained by an axonal origin of
spikelets: in the single-cell case, action potentials are generated in the axon
but fail to activate the soma. Such spikelets can be evoked by dendritic input.
Alternatively, spikelets resulting from axoaxonal gap junction coupling with a
large (greater than several hundred MUm) distance between the somata of the
coupled cells are also consistent with the data. Our results demonstrate that a
cell firing a somatic spikelet generates a detectable extracellular potential
that is different from the action potential-correlated extracellular waveform
generated by the same cell and recorded at the same location. This, together with
the absence of a refractory period between action potentials and spikelets,
implies that spikelets and action potentials generated in one cell may easily get
misclassified in extracellular recordings as two different cells, albeit they
both constitute the output of a single pyramidal neuron. NEW & NOTEWORTHY We
addressed the origin of spikelets, using compartmental models of pyramidal
neurons. Comparing our simulation results with published extracellular spikelet
recordings revealed an axonal origin of spikelets. Our results imply that action
potential- and spikelet-associated extracellular waveforms may easily get
misclassified as two different cells, albeit they both constitute the output of a
single pyramidal cell.
PMID- 29947590
TI - Hyperexcitability of brain stem pathways in cerebral palsy.
AB - Individuals with cerebral palsy (CP) experience impairments in the control of
head and neck movements, suggesting dysfunction in brain stem circuitry. To
examine if brain stem circuitry is altered in CP, we compared reflexes evoked in
the sternocleidomastoid (SCM) muscle by trigeminal nerve stimulation in adults
with CP and in age/sex-matched controls. Increasing the intensity of trigeminal
nerve stimulation produced progressive increases in the long-latency suppression
of ongoing SCM electromyography in controls. In contrast, participants with CP
showed progressively increased facilitation around the same reflex window,
suggesting heightened excitability of brain stem pathways. We also examined if
there was altered activation of cortico-brain stem pathways in response to
prenatal injury of the brain. Motor-evoked potentials (MEPs) in the SCM that were
conditioned by a prior trigeminal afferent stimulation were more facilitated in
CP compared with controls, especially in ipsilateral MEPs that are likely
mediated by corticoreticulospinal pathways. In some participants with CP, but not
in controls, a combined trigeminal nerve and cortical stimulation near threshold
intensities produced large, long-lasting responses in both the SCM and biceps
brachii muscles. We propose that the enhanced excitatory responses evoked from
trigeminal and cortical inputs in CP are produced by heightened excitability of
brain stem circuits, resulting in the augmented activation of reticulospinal
pathways. Enhanced activation of reticulospinal pathways in response to early
injury of the corticospinal tract may provide a compensated activation of the
spinal cord or, alternatively, contribute to impairments in the precise control
of head and neck functions. NEW & NOTEWORTHY This is the first study to show that
in adults with spastic cerebral palsy, activation of brain stem circuits by
cortical and/or trigeminal afferents produces excitatory responses in anterior
neck muscles compared with inhibitory responses in age/sex-matched controls. This
may reflect a more excitable reticulospinal tract in response to early brain
injury to provide a compensated activation of postural muscles. On the other
hand, a hyperexcitable brain stem may contribute to impairments in the precise
control of head and neck functions.
PMID- 29947588
TI - Estrous cycle-induced sex differences in medium spiny neuron excitatory synaptic
transmission and intrinsic excitability in adult rat nucleus accumbens core.
AB - Naturally occurring hormone cycles in adult female humans and rodents create a
dynamic neuroendocrine environment. These cycles include the menstrual cycle in
humans and its counterpart in rodents, the estrous cycle. These hormone
fluctuations induce sex differences in the phenotypes of many behaviors,
including those related to motivation, and associated disorders such as
depression and addiction. This suggests that the neural substrate instrumental
for these behaviors, including the nucleus accumbens core (AcbC), likewise
differs between estrous cycle phases. It is unknown whether the
electrophysiological properties of AcbC output neurons, medium spiny neurons
(MSNs), change between estrous cycle phases. This is a critical knowledge gap
given that MSN electrophysiological properties are instrumental for determining
AcbC output to efferent targets. Here we test whether the intrinsic
electrophysiological properties of adult rat AcbC MSNs differ across female
estrous cycle phases and from males. We recorded MSNs with whole cell patch-clamp
technique in two experiments, the first using gonad-intact adult males and
females in differing phases of the estrous cycle and the second using
gonadectomized males and females in which the estrous cycle was eliminated. MSN
intrinsic electrophysiological and excitatory synaptic input properties robustly
changed between female estrous cycle phases and males. Sex differences in MSN
electrophysiology disappeared when the estrous cycle was eliminated. These novel
findings indicate that AcbC MSN electrophysiological properties change across the
estrous cycle, providing a new framework for understanding how biological sex and
hormone cyclicity regulate motivated behaviors and other AcbC functions and
disorders. NEW & NOTEWORTHY This research is the first demonstration that medium
spiny neuron electrophysiological properties change across adult female hormone
cycle phases in any striatal region. This influence of estrous cycle engenders
sex differences in electrophysiological properties that are eliminated by
gonadectomy. Broadly, these findings indicate that adult female hormone cycles
are an important factor for neurophysiology.
PMID- 29947589
TI - Adult mouse sensory neurons on microelectrode arrays exhibit increased
spontaneous and stimulus-evoked activity in the presence of interleukin-6.
AB - Following inflammation or injury, sensory neurons located in the dorsal root
ganglia (DRG) may exhibit increased spontaneous and/or stimulus-evoked activity,
contributing to chronic pain. Current treatment options for peripherally mediated
chronic pain are highly limited, driving the development of cell- or tissue-based
phenotypic (function-based) screening assays for peripheral analgesic and
mechanistic lead discovery. Extant assays are often limited by throughput,
content, use of tumorigenic cell lines, or tissue sources from immature
developmental stages (i.e., embryonic or postnatal). Here, we describe a protocol
for culturing adult mouse DRG neurons on substrate-integrated multiwell
microelectrode arrays (MEAs). This approach enables multiplexed measurements of
spontaneous as well as stimulus-evoked extracellular action potentials from large
populations of cells. The DRG cultures exhibit stable spontaneous activity from 9
to 21 days in vitro. Activity is readily evoked by known chemical and physical
agonists of sensory neuron activity such as capsaicin, bradykinin, PGE2, heat,
and electrical field stimulation. Most importantly, we demonstrate that both
spontaneous and stimulus-evoked activity may be potentiated by incubation with
the inflammatory cytokine interleukin-6 (IL-6). Acute responsiveness to IL-6 is
inhibited by treatment with a MAPK-interacting kinase 1/2 inhibitor,
cercosporamide. In total, these findings suggest that adult mouse DRG neurons on
multiwell MEAs are applicable to ongoing efforts to discover peripheral analgesic
and their mechanisms of action. NEW & NOTEWORTHY This work describes
methodologies for culturing spontaneously active adult mouse dorsal root ganglia
(DRG) sensory neurons on microelectrode arrays. We characterize spontaneous and
stimulus-evoked adult DRG activity over durations consistent with pharmacological
interventions. Furthermore, persistent hyperexcitability could be induced by
incubation with inflammatory cytokine IL-6 and attenuated with cercosporamide, an
inhibitor of the IL-6 sensitization pathway. This constitutes a more
physiologically relevant, moderate-throughput in vitro model for peripheral
analgesic screening as well as mechanistic lead discovery.
PMID- 29947591
TI - Detecting multivariate cross-correlation between brain regions.
AB - The problem of identifying functional connectivity from multiple time series data
recorded in each of two or more brain areas arises in many neuroscientific
investigations. For a single stationary time series in each of two brain areas
statistical tools such as cross-correlation and Granger causality may be applied.
On the other hand, to examine multivariate interactions at a single time point,
canonical correlation, which finds the linear combinations of signals that
maximize the correlation, may be used. We report here a new method that produces
interpretations much like these standard techniques and, in addition, 1) extends
the idea of canonical correlation to 3-way arrays (with dimensionality number of
signals by number of time points by number of trials), 2) allows for
nonstationarity, 3) also allows for nonlinearity, 4) scales well as the number of
signals increases, and 5) captures predictive relationships, as is done with
Granger causality. We demonstrate the effectiveness of the method through
simulation studies and illustrate by analyzing local field potentials recorded
from a behaving primate. NEW & NOTEWORTHY Multiple signals recorded from each of
multiple brain regions may contain information about cross-region interactions.
This article provides a method for visualizing the complicated interdependencies
contained in these signals and assessing them statistically. The method combines
signals optimally but allows the resulting measure of dependence to change, both
within and between regions, as the responses evolve dynamically across time. We
demonstrate the effectiveness of the method through numerical simulations and by
uncovering a novel connectivity pattern between hippocampus and prefrontal cortex
during a declarative memory task.
PMID- 29947592
TI - Blunted cardiovascular responses to exercise in Parkinson's disease patients:
role of the muscle metaboreflex.
AB - Patients with Parkinson's disease (PD) exhibit attenuated cardiovascular
responses to exercise. The underlying mechanisms that are potentially
contributing to these impairments are not fully understood. Therefore, we sought
to test the hypothesis that patients with PD exhibit blunted cardiovascular
responses to isolated muscle metaboreflex activation following exercise. For
this, mean blood pressure, cardiac output, and total peripheral resistance were
measured using finger photoplethysmography and the Modelflow method in 11
patients with PD [66 +/- 2 yr; Hoehn and Yahr score: 2 +/- 1 a.u.; time since
diagnosis: 7 +/- 1 yr; means +/- SD) and 9 age-matched controls (66 +/- 3 yr).
Measurements were obtained at rest, during isometric handgrip exercise performed
at 40% maximal voluntary contraction, and during postexercise ischemia. Also, a
cold pressor test was assessed to confirm that blunted cardiovascular responses
were specific to exercise and not representative of generalized sympathetic
responsiveness. Changes in mean blood pressure were attenuated in patients with
PD during handgrip (PD: ?25 +/- 2 mmHg vs. controls: ?31 +/- 3 mmHg; P < 0.05),
and these group differences remained during postexercise ischemia (?17 +/- 1 mmHg
vs. ?26 +/- 1 mmHg, respectively; P < 0.01). Additionally, changes in total
peripheral resistance were attenuated during exercise and postexercise ischemia,
indicating blunted reflex vasoconstriction in patients with PD. Responses to cold
pressor test did not differ between groups, suggesting no group differences in
generalized sympathetic responsiveness. Our results support the concept that
attenuated cardiovascular responses to exercise observed in patients with PD are,
at least in part, explained by an altered skeletal muscle metaboreflex. NEW &
NOTEWORTHY Patients with Parkinson's disease (PD) presented blunted
cardiovascular responses to exercise. We showed that cardiovascular response
evoked by the metabolic component of the exercise pressor reflex is blunted in
patients with PD. Furthermore, patients with PD presented similar pressor
response during the cold pressor test compared with age-matched controls.
Altogether, our results support the hypothesis that attenuated cardiovascular
responses to exercise observed in patients with PD are mediate by an altered
skeletal muscle metaboreflex.
PMID- 29947593
TI - The Critical Stability Task: Quantifying sensory-motor control during ongoing
movement in non-human primates.
AB - Everyday behaviors require that we interact with the environment, using sensory
information in an ongoing manner to guide our actions. Yet, by design, many of
the tasks used in primate neurophysiology laboratories can be performed with
limited sensory guidance. As a consequence, our knowledge about the neural
mechanisms of motor control is largely limited to the feedforward aspects of the
motor command. To study the feedback aspects of volitional motor control, we
adapted the Critical Stability Task (CST) from the human performance literature
(Jex et al. 1966). In the CST, our monkey subjects interact with an inherently
unstable (i.e., divergent) virtual system and must generate sensory-guided
actions to stabilize it about an equilibrium point. The difficulty of the CST is
determined by a single parameter, which allows us to quantitatively establish the
limits of performance in the task for different sensory feedback conditions. Two
monkeys learned to perform the CST with visual or vibrotactile feedback.
Performance was better under visual feedback, as expected, but both monkeys were
able to utilize vibrotactile feedback to successfully perform the CST. We also
observed changes in behavioral strategy as the task became more challenging. The
CST will have value for basic science investigations of the neural basis of
sensory-motor integration during ongoing actions, and it may also provide value
for the design and testing of bidirectional brain computer interface systems.
PMID- 29947594
TI - Effects of pruritogens and algogens on rostral ventromedial medullary (RVM) ON
and OFF cells.
AB - RVM ON- and OFF cells are thought to facilitate and inhibit spinal nociceptive
transmission, respectively. However, it is unknown how ON and OFF cells respond
to pruritic stimuli or how they contribute to descending modulation of spinal
itch signaling. In pentobarbital-anesthetized mice, single-unit recordings were
made in RVM from ON and OFF cells identified by their respective increase or
decrease in firing that occurred just prior to nocifensive hindlimb withdrawal
elicited by paw pinch. Of RVM ON cells, 75% (21/28) were excited by intradermal
(id) histamine, 50% (10/20) by id chloroquine, and 75% (27/36) by id capsaicin.
Most chemically-responsive units also responded to a scratch stimulus applied to
the injected hindpaw. Few ON cells responded to id injection of vehicle (saline:
5/32; Tween 2/17), but still responded to scratching. For OFF cells, id histamine
and scratching inhibited 32% (6/19) with no effect of histamine in the remainder.
Id chloroquine inhibited 44% (4/9) and id capsaicin inhibited 61% (11/18) of OFF
cells. Few OFF cells were affected by vehicles (Tween: 1 inhibited, 7 unaffected;
saline: 3 excited, 1 inhibited, 8 unaffected). Both ON and OFF cells that
responded to one chemical usually also responded to others, while units
unresponsive to the first-tested chemical tended not to respond to others. These
results indicate that ascending pruriceptive signals activate RVM ON cells and
inhibit RVM OFF cells. These effects are considered to facilitate and disinhibit
spinal pain transmission, respectively. It is currently not clear if spinal itch
transmission is similarly modulated.
PMID- 29947595
TI - Motor planning perturbation: muscle activation and reaction time.
AB - Reaction time (RT) is the time interval between the appearance of a stimulus and
initiation of a motor response. Within RT, two processes occur, selection of
motor goals and motor planning. An unresolved question is whether perturbation to
the motor planning component of RT slows the response and alters the voluntary
activation of muscle. The purpose of this study was to determine how the
modulation of muscle activity during an RT response changes with motor plan
perturbation. Twenty-four young adults (20.5 +/-1.1 yr, 13 women) performed 15
trials of an isometric RT task with ankle dorsiflexion using a sinusoidal
anticipatory strategy (10-20% maximum voluntary contraction). We compared the
processing part of the RT and modulation of muscle activity from 10 to 60 Hz of
the tibialis anterior (primary agonist) when the stimulus appeared at the trough
or at the peak of the sinusoidal task. We found that RT ( P = 0.003) was longer
when the stimulus occurred at the peak compared with the trough. During the time
of the reaction, the electromyography (EMG) power from 10 to 35 Hz was less at
the peak than the trough ( P = 0.019), whereas the EMG power from 35 to 60 Hz was
similar between the peak and trough ( P = 0.92). These results suggest that
perturbation to motor planning lengthens the processing part of RT and alters the
voluntary activation of the muscle by decreasing the relative amount of power
from 10 to 35 Hz. NEW & NOTEWORTHY We aimed to determine whether perturbation to
motor planning would alter the speed and muscle activity of the response. We
compared trials when a stimulus appeared at the peak or trough of an oscillatory
reaction time task. When the stimulus occurred at the trough, participants
responded faster, with greater force, and less EMG power from 10-35 Hz. We
provide evidence that motor planning perturbation slows the response and alters
the voluntary activity of the muscle.
PMID- 29947596
TI - Role of lysophosphatidic acid in ion channel function and disease.
AB - Lysophosphatidic acid (LPA) is a bioactive phospholipid that exhibits a wide
array of functions that include regulation of protein synthesis and adequate
development of organisms. LPA is present in the membranes of cells and in the
serum of several mammals and has also been shown to participate importantly in
pathophysiological conditions. For several decades it was known that LPA produces
some of its effects in cells through its interaction with specific G protein
coupled receptors, which in turn are responsible for signaling pathways that
regulate cellular function. Among the target proteins for LPA receptors are ion
channels that modulate diverse aspects of the physiology of cells and organs
where they are expressed. However, recent studies have begun to unveil direct
effects of LPA on ion channels, highlighting this phospholipid as a direct
agonist and adding to the knowledge of the field of lipid-protein interactions.
Moreover, the roles of LPA in pathophysiological conditions associated with the
function of some ion channels have also begun to be clarified, and molecular
mechanisms have been identified. This review focuses on the effects of LPA on ion
channel function under normal and pathological conditions and highlights our
present knowledge of the mechanisms by which it regulates the function and
expression of N- and T-type Ca++ channels; M-type K+ channel and inward rectifier
K+ channel subunit 2.1; transient receptor potential (TRP) melastatin 2, TRP
vanilloid 1, and TRP ankyrin 1 channels; and TWIK-related K+ channel 1 (TREK-1),
TREK-2, TWIK-related spinal cord K+ channel (TRESK), and TWIK-related arachidonic
acid-stimulated K+ channel (TRAAK).
PMID- 29947597
TI - Tune it in: mechanisms and computational significance of neuron-autonomous
plasticity.
AB - The activity of a neural network is a result of synaptic signals that convey the
communication between neurons and neuron-based intrinsic currents that determine
the neuron's input-output transfer function. Ample studies have demonstrated that
cell-based excitability, and in particular intrinsic excitability, is modulated
by learning and that these modifications play a key role in learning-related
behavioral changes. The field of cell-based plasticity is largely growing, and it
entails numerous experimental findings that demonstrate a large diversity of
currents that are affected by learning. The diverse effect of learning on the
neuron's excitability emphasizes the need for a framework under which cell-based
plasticity can be categorized to enable the assessment of the computational roles
of the intrinsic modifications. We divide the domain of cell-based plasticity
into three main categories, where the first category entails the currents that
mediate the passive properties and single-spike generation, the second category
entails the currents that mediate spike frequency adaptation, and the third
category entails a novel learning-induced mechanism where all excitatory and
inhibitory synapses double their strength. Curiously, this elementary division
enables a natural categorization of the computational roles of these learning
induced plasticities. The computational roles are diverse and include
modification of the neuronal mode of action, such as bursting, prolonged, and
fast responsive; attention-like effect where the signal detection is improved;
transfer of the network into an active state; biasing the competition for memory
allocation; and transforming an environmental cue into a dominant cue and
enabling a quicker formation of new memories.
PMID- 29947598
TI - Hyperoxia enhances slow-wave forebrain states in urethane-anesthetized and
naturally sleeping rats.
AB - Oxygen (O2) is a crucial element for physiological functioning in mammals. In
particular, brain function is critically dependent on a minimum amount of
circulating blood levels of O2 and both immediate and lasting neural dysfunction
can result following anoxic or hypoxic episodes. Although the effects of
deficiencies in O2 levels on the brain have been reasonably well studied, less is
known about the influence of elevated levels of O2 (hyperoxia) in inspired gas
under atmospheric pressure. This is of importance due to its typical use in
surgical anesthesia, in the treatment of stroke and traumatic brain injury, and
even in its recreational or alternative therapeutic use. Using local field
potential (EEG) recordings in spontaneously breathing urethane-anesthetized and
naturally sleeping rats, we characterized the influence of different levels of O2
in inspired gases on brain states. While rats were under urethane anesthesia,
administration of 100% O2 elicited a significant and reversible increase in time
spent in the deactivated (i.e., slow-wave) state, with concomitant decreases in
both heartbeat and respiration rates. Increasing the concentration of carbon
dioxide (to 5%) in inspired gas produced the opposite result on EEG states,
mainly a decrease in the time spent in the deactivated state. Consistent with
this, decreasing concentrations of O2 (to 15%) in inspired gases decreased time
spent in the deactivated state. Further confirmation of the hyperoxic effect was
found in naturally sleeping animals where it similarly increased time spent in
slow-wave (nonrapid eye movement) states. Thus alterations of O2 in inspired air
appear to directly affect forebrain EEG states, which has implications for brain
function, as well as for the regulation of brain states and levels of forebrain
arousal during sleep in both normal and pathological conditions. NEW & NOTEWORTHY
We show that alterations of oxygen concentration in inspired air biases forebrain
EEG state. Hyperoxia increases the prevalence of slow-wave states. Hypoxia and
hypercapnia appear to do the opposite. This suggests that oxidative metabolism is
an important stimulant for brain state.
PMID- 29947600
TI - Marital Violence During War Conflict: The Lived Experience of Syrian Refugee
Women.
AB - INTRODUCTION: Marital violence increases during times of war. This study aims to
describe the lived experience of marital violence toward Syrian refugee women
during the current war in Syria. DESIGN: A descriptive phenomenological research
methodology was used to conduct semistructured interviews with 16 purposively
selected Syrian refugee women residing in displacement centers in Jordan.
Colaizzi's steps of data analysis were used. RESULTS: Four themes identified were
identified: (1) Loss, insecurity, and suffering; (2) Shame and humiliation; (3)
Justifying and enduring marital violence; and (4) Ways of coping with marital
violence. CONCLUSION: The Syrian War conflict changed women's lifeway and created
a context for marital violence. Study findings suggests addressing marital
violence during wartime and allocating resources to provide care and support of
victims of violence in the displaced countries.
PMID- 29947599
TI - Control of redundant pointing movements involving the wrist and forearm.
AB - The musculoskeletal system can move in more ways than are strictly necessary,
allowing many tasks to be accomplished with a variety of limb configurations. Why
some configurations are preferred has been a focus of motor control research, but
most studies have focused on shoulder-elbow or whole arm movements. This study
focuses on movements involving forearm pronation-supination (PS), wrist flexion
extension (FE), and wrist radial-ulnar deviation (RUD) and elucidates how these
three degrees of freedom (DOF) combine to perform the common task of pointing,
which only requires two DOF. Although pointing is more sensitive to FE and RUD
than to PS and could be easily accomplished with FE and RUD alone, subjects tend
to involve a small amount of PS. However, why we choose this behavior has been
unknown and is the focus of this paper. With the use of a second-order model with
lumped parameters, we tested a number of plausible control strategies involving
minimization of work, potential energy, torque, and path length. None of these
control schemes robustly predicted the observed behavior. However, an alternative
control scheme, hypothesized to control the DOF that were most important to the
task (FE and RUD) and ignore the less important DOF (PS), matched the observed
behavior well. In particular, the behavior observed in PS appears to be a
mechanical side effect caused by unopposed interaction torques. We conclude that
moderately sized pointing movements involving the wrist and forearm are
controlled by ignoring forearm rotation even though this strategy does not
robustly minimize work, potential energy, torque, or path length. NEW &
NOTEWORTHY Many activities require us to point our hands in a given direction
using wrist and forearm rotations. Although there are infinitely many ways to do
this, we tend to follow a stereotyped pattern. Why we choose this pattern has
been unknown and is the focus of this paper. After testing a variety of
hypotheses, we conclude that the pattern results from a simplifying strategy in
which we focus on wrist rotations and ignore forearm rotation.
PMID- 29947601
TI - Identification of recombinant coxsackievirus A6 variants in hand, foot and mouth
disease in Nanjing, China, 2013.
AB - PURPOSE: Enteroviruses (EV) 71 and coxsackievirus A (CVA) 16 are the most
prevalent EV serotypes responsible for hand, foot and mouth disease (HFMD).
Nevertheless, CVA6 was found to be the leading cause of HFMD in the Nanjing area,
of China in 2013. This study aims to provide insights into the occurrence of the
emergent recombinant CVA6 through examination of the evolutionary history and the
involved recombination events. METHODOLOGY: The viral protein1 (VP1) and non
structural (NS) 2C and 3D of 28 Nanjing CVA6 strains were aligned, among which
the full-length sequences of eight strains were further characterized. RESULTS:
We revealed the co-existence of two recombinant forms (RFs), RF-A and RF-J, in
the local area. RF-J is a novel RF group, comprising a proportion of local and
Shanghai CVA6 strains from 2013. The appearance of RF-J CVA6 strains was most
likely the result of two recombination events, with the co-circulating CVA4 and
CVA8 providing the regions beyond positions 4001~4045 and 4866~4873,
respectively. Evolutionary history analysis showed that the VP1 sequences of RF-J
derived from RF-A, which was also probably the ancestor of several other RF
groups. The 3D region of RF-J was closely related to CVA8. The point in time of
emergence of the most recent common ancestor (tMRCA) of RF-J in China was
estimated to be around 2011 in both terms of VP1 and 3D region. CONCLUSION: The
emerging recombinant CVA6 variants belong to a novel RF-J group which was most
likely formed by at least two recombination events. Continued monitoring on the
geographical distribution of various CVA6 RFs is essential.
PMID- 29947602
TI - Xinfangfangia soli gen. nov., sp. nov., isolated from a diuron-polluted soil.
AB - A novel Gram-staining-negative, non-motile and rod-shaped bacterial strain ZQBWT,
which was isolated from a diuron-polluted soil collected near Nanjing, PR China,
was investigated for its taxonomic position by a polyphasic approach. ZQBWT grew
well at pH 6.0-12.0 (optimum, pH 7.0), 26-35 degrees C (optimum, 30 degrees C)
and up to 0.5 % NaCl (optimally the absence of NaCl) in R2A broth. The major
fatty acids of ZQBWT were C18 : 1omega7c (82.7 %) and C18 : 0 (5.3 %). The polar
lipid profile included the major compounds phophatidylcholine,
phosphatidylglycerol and phosphatidylmethylethanolamine. The only respiratory
quinone was ubiquinone Q-10. The G+C content of genomic DNA was 67.0 mol%.
Comparisons with 16S rRNA gene sequences revealed that ZQBWT has the highest
sequence similarities with members of the genus Tabrizicola (<=95.97 %), followed
by Rhodobacter(<=95.96 %) and Falsirhodobacter(95.95 %) which all belong to the
family Rhodobacteraceaein the phylum Proteobacteria. Photosynthesis genes pufLM
were not found and photosynthesis pigments were not formed in ZQBWT. On the basis
of the results from chemotaxonomic, phenotypic and phylogenetic analysis, ZQBWT
represents a novel species of a novel genus, for which the name Xinfangfangia
soli gen. nov., sp. nov. is proposed. The type strain is ZQBWT (=KCTC
62102T=CCTCC AB 2017177T).
PMID- 29947603
TI - ICTV Virus Taxonomy Profile: Baculoviridae.
AB - The family Baculoviridae comprises large viruses with circular dsDNA genomes
ranging from 80 to 180 kbp. The virions consist of enveloped, rod-shaped
nucleocapsids and are embedded in distinctive occlusion bodies measuring 0.15-5
um. The occlusion bodies consist of a matrix composed of a single viral protein
expressed at high levels during infection. Members of this family infect
exclusively larvae of the insect orders Lepidoptera, Hymenoptera and Diptera.
This is a summary of the International Committee on Taxonomy of Viruses (ICTV)
Report on the taxonomy of the Baculoviridae, which is available at
www.ictv.global/report/baculoviridae.
PMID- 29947604
TI - Are people with psychiatric disorders violent?
PMID- 29947607
TI - Effects of extended-release naltrexone on the brain response to drug-related
stimuli in patients with opioid use disorder.
AB - BACKGROUND: Heightened response to drug-related cues is a hallmark of addiction.
Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration
approved pharmacotherapy for relapse prevention in patients with opioid use
disorder (OUD). In these patients, XR-NTX has been shown to reduce brain
responses to opioid-related visual stimuli. To assess the biomarker potential of
this phenomenon, it is necessary to determine whether this effect is limited to
opioid-related stimuli and whether it is associated with key OUD symptoms.
METHODS: Using functional MRI (fMRI), we measured the brain responses to opioid
related and control (i.e., sexual and aversive) images in detoxified patients
with OUD before, during and after XR-NTX treatment. Craving and withdrawal
severity were evaluated using clinician- and self-administered instruments during
each session. RESULTS: We included 24 patients with OUD in our analysis. During
XR-NTX treatment, we found reduced responses to opioid-related stimuli in the
nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in
mOFC response was specific to the opioid-related stimuli. The reduced NAcc and
mOFC opioid cue reactivity was correlated with reduction in clinician-assessed
and self-reported withdrawal symptoms, respectively. LIMITATIONS: The study was
not placebo-controlled owing to ethical, safety and feasibility concerns.
CONCLUSION: Extended-release naltrexone reduces the NAcc and mOFC cue reactivity
in patients with OUD. This effect is specific to opioid-related stimuli in the
mOFC only. The reduction in neural response to opioid-related stimuli is more
robust in patients with greater decline in withdrawal severity. Our results
support the clinical utility of mesocorticolimbic cue reactivity in monitoring
the XR-NTX treatment outcomes and highlight the link between opioid withdrawal
symptomatology and neural opioid cue reactivity.
PMID- 29947606
TI - Examining cognition across the bipolar/schizophrenia diagnostic spectrum.
AB - BACKGROUND: Cognitive impairments are well-established features of schizophrenia,
but there is ongoing debate about the nature and degree of cognitive impairment
in patients with schizoaffective disorder and bipolar disorder. We hypothesized
that there is a spectrum of increasing impairment from bipolar disorder to
schizoaffective disorder bipolar type, to schizoaffective disorder depressive
type and schizophrenia. METHODS: We compared performance on the Measurement and
Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus
Cognitive Battery between participants with schizophrenia (n = 558),
schizoaffective disorder depressive type (n = 112), schizoaffective disorder type
(n = 76), bipolar disorder (n = 78) and healthy participants (n = 103) using
analysis of covariance with post hoc comparisons. We conducted an ordinal
logistic regression to examine whether cognitive impairments followed the
hypothesized spectrum from bipolar disorder (least severe) to schizophrenia (most
severe). In addition to categorical diagnoses, we addressed the influence of
symptom domains, examining the association between cognition and mania,
depression and psychosis. RESULTS: Cognitive impairments increased in severity
from bipolar disorder to schizoaffective disorder bipolar type, to schizophrenia
and schizoaffective disorder depressive type. Participants with schizophrenia and
schizoaffective disorder depressive type showed equivalent performance (d = 0.07,
p = 0.90). The results of the ordinal logistic regression were consistent with a
spectrum of deficits from bipolar disorder to schizoaffective disorder bipolar
type, to schizophrenia/schizoaffective disorder depressive type (odds ratio =
1.98, p < 0.001). In analyses of the associations between symptom dimensions and
cognition, higher scores on the psychosis dimension were associated with poorer
performance (B = 0.015, standard error = 0.002, p < 0.001). LIMITATIONS: There
were fewer participants with schizoaffective disorder and bipolar disorder than
schizophrenia. Despite this, our analyses were robust to differences in group
sizes, and we were able to detect differences between groups. CONCLUSION:
Cognitive impairments represent a symptom dimension that cuts across traditional
diagnostic boundaries.
PMID- 29947608
TI - Correction: Enhanced corticobulbar excitability in chronic smokers during visual
exposure to cigarette smoking cues.
PMID- 29947605
TI - Genetic variability in scaffolding proteins and risk for schizophrenia and autism
spectrum disorders: a systematic review.
AB - Scaffolding proteins represent an evolutionary solution to controlling the
specificity of information transfer in intracellular networks. They are highly
concentrated in complexes located in specific subcellular locations. One of these
complexes is the postsynaptic density of the excitatory synapses. There,
scaffolding proteins regulate various processes related to synaptic plasticity,
such as glutamate receptor trafficking and signalling, and dendritic structure
and function. Most scaffolding proteins can be grouped into 4 main families:
discs large (DLG), discs-large-associated protein (DLGAP), Shank and Homer. Owing
to the importance of scaffolding proteins in postsynaptic density architecture,
it is not surprising that variants in the genes that code for these proteins have
been associated with neuropsychiatric diagnoses, including schizophrenia and
autism-spectrum disorders. Such evidence, together with the clinical,
neurobiological and genetic overlap described between schizophrenia and autism
spectrum disorders, suggest that alteration of scaffolding protein dynamics could
be part of the pathophysiology of both. However, despite the potential importance
of scaffolding proteins in these psychiatric conditions, no systematic review has
integrated the genetic and molecular data from studies conducted in the last
decade. This review has the following goals: to systematically analyze the
literature in which common and/or rare genetic variants (single nucleotide
polymorphisms, single nucleotide variants and copy number variants) in the
scaffolding family genes are associated with the risk for either schizophrenia or
autism-spectrum disorders; to explore the implications of the reported genetic
variants for gene expression and/or protein function; and to discuss the
relationship of these genetic variants to the shared genetic, clinical and
cognitive traits of schizophrenia and autism-spectrum disorders.
PMID- 29947610
TI - The maternal brain in women with a history of early-life maltreatment: an
imagination-based fMRI study of conflictual versus pleasant interactions with
children.
AB - BACKGROUND: Early-life maltreatment has severe consequences for the affected
individual, and it has an impact on the next generation. To improve understanding
of the intergenerational effects of abuse, we investigated the consequences of
early-life maltreatment on maternal sensitivity and associated brain mechanisms
during mother-child interactions. METHODS: In total, 47 mothers (22 with a
history of physical and/or sexual childhood abuse and 25 without, all without
current mental disorders) took part in a standardized real-life interaction with
their 7- to 11-year-old child (not abused) and a subsequent functional imaging
script-driven imagery task. RESULTS: Mothers with early-life maltreatment were
less sensitive in real-life mother-child interactions, but while imagining
conflictual interactions with their child, they showed increased activation in
regions of the salience and emotion-processing network, such as the amygdala,
insula and hippocampus. This activation pattern was in contrast to that of
mothers without early-life maltreatment, who showed higher activations in those
regions in response to pleasant mother-child interactions. Mothers with early
life maltreatment also showed reduced functional connectivity between regions of
the salience and the mentalizing networks. LIMITATIONS: Region-of-interest
analyses, which were performed in addition to whole-brain analyses, were
exploratory in nature, because they were not further controlled for multiple
comparisons. CONCLUSION: Results suggest that for mothers with early-life
maltreatment, conflictual interactions with their child may be more salient and
behaviourally relevant than pleasant interactions, and that their salience
network is poorly modulated by the brain regions involved in mentalizing
processes. This activation pattern offers new insights into the mechanisms behind
the intergenerational effects of maltreatment and into options for reducing these
effects.
PMID- 29947609
TI - Abnormal dynamic functional connectivity of amygdalar subregions in untreated
patients with first-episode major depressive disorder.
AB - BACKGROUND: Accumulating evidence supports the concept of the amygdala as a
complex of structurally and functionally heterogeneous nuclei rather than as a
single homogeneous structure. However, changes in resting-state functional
connectivity in amygdalar subregions have not been investigated in major
depressive disorder (MDD). Here, we explored whether amygdalar subregions -
including the laterobasal, centromedial (CM) and superficial (SF) areas -
exhibited distinct disruption patterns for different dynamic functional
connectivity (dFC) properties, and whether these different properties were
correlated with clinical information in patients with MDD. METHODS: Thirty
untreated patients with first-episode MDD and 62 matched controls were included.
We assessed between-group differences in the mean strength of dFC in each
amygdalar subregion in the whole brain using general linear model analysis.
RESULTS: The patients with MDD showed decreased strength in positive dFC between
the left CM/SF and brainstem and between the left SF and left thalamus; they
showed decreased strength in negative dFC between the left CM and right superior
frontal gyrus (p < 0.05, family-wise error-corrected). We found significant
positive correlations between age at onset and the mean positive strength of dFC
in the left CM/brainstem in patients with MDD. LIMITATIONS: The definitions of
amygdalar subregions were based on a cytoarchitectonic delineation, and the
temporal resolution of the fMRI was slow (repetition time = 2 s). CONCLUSION:
These findings confirm the distinct dynamic functional pathway of amygdalar
subregions in MDD and suggest that the limbic-cortical-striato-pallido-thalamic
circuitry plays a crucial role in the early stages of MDD.
PMID- 29947611
TI - Social anxiety disorder in schizophrenia: a neglected, yet potentially important
comorbidity.
PMID- 29947612
TI - Stable high-performance perovskite solar cells based on inorganic electron
transporting bi-layers.
AB - As one of the significant electron transporting materials (ETMs) in efficient
planar heterojunction perovskite solar cells (PSCs), SnO2 can collect/transfer
photo-generated carriers produced in perovskite active absorbers and suppress the
carrier recombination at interfaces. In this study, we demonstrate that a mild
solution-processed SnO2 compact layer can be an eminent ETM for planar
heterojunction PSCs. Here, the device based on chemical-bath-deposited SnO2
electron transporting layer (ETL) exhibits a power conversion efficiency (PCE) of
16.10% and with obvious hysteresis effect (hysteresis index = 19.5%), owing to
the accumulation and recombination of charge carriers at the SnO2/perovskite
interface. In order to improve the carrier dissociation and transport process, an
ultrathin TiO2 film was deposited on the top of the SnO2 ETL passivating
nonradiative recombination center. The corresponding device based on the
TiO2@SnO2 electron transporting bi-layer (ETBL) exhibited a high PCE (17.45%) and
a negligible hysteresis effect (hysteresis index = 1.5%). These findings indicate
that this facile solution-processed TiO2@SnO2 ETBL paves a scalable and
inexpensive way for fabricating hysteresis-less and high-performance PSCs.
PMID- 29947613
TI - Investigating energy deposition within cell populations using Monte Carlo
simulations.
AB - In this work, we develop multicellular models of healthy and cancerous human soft
tissues, which are used to investigate energy deposition in subcellular targets,
quantify the microdosimetric spread in a population of cells, and determine how
these results depend on model details. Monte Carlo (MC) tissue models combining
varying levels of detail on different length scales are developed:
microscopically-detailed regions of interest (>1500 explicitly-modelled cells)
are embedded in bulk tissue phantoms irradiated by photons (20 keV-1.25 MeV).
Specific energy (z; energy imparted per unit mass) is scored in nuclei and
cytoplasm compartments using the EGSnrc user-code egs_chamber; specific energy
mean, [Formula: see text], standard deviation, [Formula: see text], and
distribution, [Formula: see text], are calculated for a variety of macroscopic
doses, D. MC-calculated [Formula: see text] are compared with normal
distributions having the same mean and standard deviation. For ~mGy doses, there
is considerable variation in energy deposition (microdosimetric spread)
throughout a cell population: e.g. for 30 keV photons irradiating melanoma with
7.5 MUm cell radius and 3 MUm nuclear radius, [Formula: see text] for nuclear
targets is [Formula: see text], and the fraction of nuclei receiving no energy
deposition, f z=0, is 0.31 for a dose of 10 mGy. If cobalt-60 photons are
considered instead, then [Formula: see text] decreases to [Formula: see text],
and f z=0 decreases to 0.036. These results correspond to randomly arranged cells
with cell/nucleus sizes randomly sampled from a normal distribution with a
standard deviation of 1 MUm. If cells are arranged in a hexagonal lattice and
cell/nucleus sizes are uniform throughout the population, then [Formula: see
text] decreases to [Formula: see text] and [Formula: see text] for 30 keV and
cobalt-60, respectively; f z=0 decreases to 0.25 and 0.000 94 for 30 keV and
cobalt-60, respectively. Thus, specific energy distributions are sensitive to
cell/nucleus sizes and their distributions: variations in specific energy
deposited over a cell population are underestimated if targets are assumed to be
uniform in size compared with more realistic variation in target size. Bulk
tissue dose differs from [Formula: see text] for nuclei (cytoplasms) by up to
[Formula: see text] ([Formula: see text]) across all cell/nucleus sizes, bulk
tissues, and incident photon energies, considering a 50 mGy dose level. Overall,
results demonstrate the importance of microdosimetric considerations at low
doses, and indicate the sensitivity of energy deposition within subcellular
targets to incident photon energy, dose level, elemental compositions, and
microscopic tissue model.
PMID- 29947614
TI - Nodeless superconductivity in the cage-type superconductor Sc5Ru6Sn18 with
preserved time-reversal symmetry.
AB - We report the single-crystal synthesis and detailed investigations of the cage
type superconductor Sc5Ru6Sn18, using powder x-ray diffraction (XRD),
magnetization, specific-heat and muon-spin relaxation (uSR) measurements.
Sc5Ru6Sn18 crystallizes in a tetragonal structure (space group I41/acd) with
lattice parameters a = 1.387(3) nm and c = 2.641(5) nm. Both DC and AC
magnetization measurements prove the type-II superconductivity in Sc5Ru6Sn18 with
T c ~ 3.5(1) K, a lower critical field [Formula: see text] = 157(9) Oe and an
upper critical field, [Formula: see text] = 26(1) kOe. The zero-field
electronic specific-heat data are well fitted using a single-gap BCS model, with
[Formula: see text] = 0.64(1) meV. The Sommerfeld constant gamma varies
linearly with the applied magnetic field, indicating s-wave superconductivity in
Sc5Ru6Sn18. Specific-heat and transverse-field (TF) uSR measurements reveal that
Sc5Ru6Sn18 is a superconductor with strong electron-phonon coupling, with TF-uSR
also suggesting a single-gap s-wave character of the superconductivity.
Furthermore, zero-field uSR measurements do not detect spontaneous magnetic
fields below T c, hence implying that time-reversal symmetry is preserved in
Sc5Ru6Sn18.
PMID- 29947615
TI - Evidence for weak collective pinning and deltal pinning in topological
superconductor Cu x Bi2Se3.
AB - We investigated the vortex pinning behavior in the single crystal topological
superconductor Cu0.10Bi2Se3 with a pronounced anisotropic peak effect. A weak
collective pinning regime is clarified from the power-law behavior in [Formula:
see text] and the small critical current density ratio of [Formula: see text] ~
10-5 ([Formula: see text] is the critical current density, [Formula: see text] is
the depairing current density). The spatial variation of the charge-carrier mean
free path induced pinning is evidenced and probably results from the well-defined
atomic defects. Within the framework of collective pinning theory, we computed
the values of the correlated length and volume at 1.8 K, which start declining
prior to the onset field of the peak effect [Formula: see text], demonstrating
the vortex lattices already suffered a preferential collapse ahead of the peak
effect turns up. Thus, the peak effect can be understood by elastic moduli
softening near the upper critical field [Formula: see text]. We suggest Cu x
Bi2Se3 is a prototype topological material for investigating the vortex pinning
dynamics associated with the peak effect phenomenon.
PMID- 29947616
TI - Reconfiguring ferromagnetic microrod chains by alternating two orthogonal
magnetic fields.
AB - It is well-known that ferromagnetic microrods form linear chains under an
external uniform magnetic field B and the chain length is strongly dependent on
the applied field, the applied time duration, and the microrod density. When the
chains become long enough and the B-field switches to its orthogonal direction,
an irreversible morphological transition, i.e. a parallel linear chain array to a
2D network, is observed. The formation of the network depends on the ratio of the
average chain length L and separation D, L/D, as well as the magnitude of the
changed B-field. When the chain pattern has an L/D larger than a critical value,
the network structure will be formed. Such a critical L/D ratio is a monotonic
function of B, which determines the bending length of each magnetic chain during
the change of B-fields. This morphological change triggered by external magnetic
field can be used as scaffolds or building blocks for biological applications or
design smart materials.
PMID- 29947617
TI - Quasibound states in single-layer graphene quantum rings.
AB - We study the quasi-bound state (QBS) spectra of the graphene quantum rings
created by an axially symmetric electrostatic potential. Detailed calculations
are carried out for the case of rectangular confinement potentials using the T
matrix and/or the local density of states approaches. Obtained results are
analyzed in detail with respect to the two principal characters of QBSs, the
(resonant) level position and the level width. A unique relation is established
between the QBS-spectrum of a quantum ring under study and the resonant levels
formed in the corresponding one-dimensional rectangular potential barrier.
Studies are realized in both cases of zero and non-zero mass.
PMID- 29947618
TI - Simulating transvertebral ultrasound propagation with a multi-layered ray
acoustics model.
AB - The simulation accuracy of transvertebral ultrasound propagation using a multi
layered ray acoustics model based on CT-derived vertebral geometry was
investigated through comparison with experimental measurements of pressure fields
in ex vivo human vertebral foramen. A spherically focused transducer (5 cm
diameter, f-number 1.2, 514 kHz) was geometrically focused to the centre of
individual thoracic vertebral foramen, through the posterior bony elements.
Transducer propagation paths through the laminae and the spinous processes were
tested. Simulation transducer-vertebra configurations were registered to
experiment transducer-vertebra configurations, and simulation accuracy of the
simulation model was evaluated for predicting maximum transmitted pressure to the
canal, voxel pressure in the canal, and focal distortion. Accuracy in predicting
maximum transmitted pressure was calculated by vertebra, and it is shown that
simulation predicts maximum pressure with a greater degree of accuracy than a
vertebra-specific insertion loss. Simulation error in voxel pressure was
evaluated using root-mean-square error and cross-correlation, and found to be
similar to the water-only case. Simulation accuracy in predicting focal
distortion was evaluated by comparing experiment and simulation maximum pressure
location and weighted >50% focal volume location. Average simulation error
across all measurements and simulations in maximum pressure location and weighted
>50% focal volume location were 2.3 mm and 1.5 mm, respectively. These errors
are small relative to the dimensions of the transducer focus (4.9 mm full width
half maximum), the spinal cord (10 mm diameter), and vertebral canal diameter (15
20 mm diameter). These results suggest that ray acoustics can be applied to
simulating transvertebral ultrasound propagation.
PMID- 29947619
TI - The role of incidence angle in the morphology evolution of Ge surfaces irradiated
by medium-energy Au ions.
AB - Germanium (Ge) surfaces have been irradiated with 26 keV gold (Au) ions at a
constant fluence and at incidence angles varying from 0 degrees to 85 degrees .
The evolution of the emerging nanostructures is studied by atomic force
microscopy (AFM), scanning electron microscopy, x-ray photoelectron spectroscopy
(XPS), and cross-sectional transmission electron microscopy. The obtained results
are compared with findings reported in the literature. Periodic rippled patterns
with the wave vector parallel to the projection of the ion beam direction onto
the Ge surface develop between 30 degrees and 45 degrees . From 75 degrees the
morphology changes from parallel-mode ripples to parallel-mode terraces, and by
further increasing the incidence angle the terraces coarsen and show a
progressive break-up of the front facing the ion beam. No perpendicular-mode
ripples or terraces have been observed. The analysis of the AFM height profiles
and slope distributions shows in the 45 degrees -85 degrees range an angular
dependence of the temporal scale for the onset of nonlinear processes. For
incidence angles below 45 degrees , the surface develops a sponge-like structure,
which persists at higher incidence angles on the top and partially on the face of
the facets facing the ion beam. The XPS and the energy-dispersive x-ray
spectroscopy evidence the presence of Au nano-aggregates of different sizes for
the different incidence angles. This study points out the peculiar behavior of Ge
surfaces irradiated with medium-energy Au ions and warns about the differences to
be faced when trying to build a universal framework for the description of
semiconductor pattern evolution under ion-beam irradiation.
PMID- 29947620
TI - In vitro and in vivo stability of black-platinum coatings on flexible, polymer
microECoG arrays.
AB - OBJECTIVE: Intracranial EEG (iEEG) or micro-electrocorticography (uECoG)
microelectrodes offer high spatial resolution in recordings of neuronal activity
from the exposed brain surface. Reliability of dielectric substrates and
conductive materials of these devices are under intensive research in terms of
functional stability in biological environments. APPROACH: The aim of our study
is to investigate the stability of electroplated platinum recording sites on 16
channel, 8 micron thick, polyimide based, flexible uECoG arrays implanted
underneath the skull of rats. Scanning electron microscopy and electrochemical
impedance spectroscopy was used to reveal changes in either surface morphology or
interfacial characteristics. The effect of improved surface area (roughness
factor = 23 +/- 0.12) on in vivo recording capability was characterized in
both acute and chronic experiments. MAIN RESULTS: Besides the expected reduction
in thermal noise and enhancement in signal-to-noise ratio (up to 39.8), a slight
increase in the electrical impedance of individual sites was observed, as a
result of changes in the measured interfacial capacitance. In this paper, we also
present technology processes and protocols in detail to use such implants without
crack formation of the porous platinum surfaces. SIGNIFICANCE: Our findings imply
that black-platinum coating deposited on the recording sites of flexible
microelectrodes (20 microns in diameter) provides a stable interface between
tissue and device.
PMID- 29947621
TI - Investigation of the temperature dependent field emission from individual ZnO
nanowires for evidence of field-induced hot electrons emission.
AB - ZnO nanowires as field emitters have important applications in flat panel display
and x-ray source. Understanding the intrinsic field emission mechanism is crucial
for further improving the performance of ZnO nanowire field emitters. In this
article, the temperature dependent field emission from individual ZnO nanowires
was investigated by an in situ measurement in ultra-high vacuum. The divergent
temperature-dependent Fowler-Nordheim plots is found in the low field region. A
field-induced hot electrons emission model, that takes into account penetration
length, is proposed to explain the results. The carrier density and temperature
dependence of the field-induced hot electrons emission current are derived
theoretically. The obtained results are consistent with the experimental results,
which could be attributed to the variation of effective electron temperature. All
of these are important for a better understanding on the field emission process
of semiconductor nanostructures.
PMID- 29947622
TI - Impact of kilobar pressures on ultrafast triazene and thiacyanine photodynamics.
AB - Very short fluorescence lifetimes evidence ultrafast deactivation of photoexcited
molecules. To unveil the underlying mechanism for two compounds exhibiting
(sub)picosecond emission dynamics, we combine femtosecond fluorescence
upconversion with high-pressure liquid-phase spectroscopy. For the triazene
berenil, the absence of a pressure dependence corroborates a bicycle-pedal motion
as deactivating process. In the thiacyanine NK88 which may undergo a bi-phasic
deactivation, our results suggest that kilobar pressures lead to a modification
of the excited-state potential energy surface, thereby changing the branching
ratio of two competing pathways and opening a possibility to steer the product
distribution of the photoreaction.
PMID- 29947623
TI - Partial least squares-discriminant analysis (PLS-DA) for classification of high
dimensional (HD) data: a review of contemporary practice strategies and knowledge
gaps.
AB - Partial least squares-discriminant analysis (PLS-DA) is a versatile algorithm
that can be used for predictive and descriptive modelling as well as for
discriminative variable selection. However, versatility is both a blessing and a
curse and the user needs to optimize a wealth of parameters before reaching
reliable and valid outcomes. Over the past two decades, PLS-DA has demonstrated
great success in modelling high-dimensional datasets for diverse purposes, e.g.
product authentication in food analysis, diseases classification in medical
diagnosis, and evidence analysis in forensic science. Despite that, in practice,
many users have yet to grasp the essence of constructing a valid and reliable PLS
DA model. As the technology progresses, across every discipline, datasets are
evolving into a more complex form, i.e. multi-class, imbalanced and colossal.
Indeed, the community is welcoming a new era called big data. In this context,
the aim of the article is two-fold: (a) to review, outline and describe the
contemporary PLS-DA modelling practice strategies, and (b) to critically discuss
the respective knowledge gaps that have emerged in response to the present big
data era. This work could complement other available reviews or tutorials on PLS
DA, to provide a timely and user-friendly guide to researchers, especially those
working in applied research.
PMID- 29947624
TI - Photodegradation of methyl thioglycolate particles as a proxy for organosulphur
containing droplets.
AB - Understanding the formation and transformation of sulphur-rich particles is of
prime importance since they contribute to the global atmospheric sulphur budget.
In this work, we performed a series of experiments on a photoactive organosulphur
compound namely, methyl thioglycolate, as a model of an organosulphur species of
marine origin. By investigating the photoproducts within levitated droplets, we
showed that elemental sulphur (alpha-S8) and sulphate (SO42-) can be
photochemically generated at the gas-liquid interface by heterogeneous
interaction with gaseous O2 and H2O. These results demonstrate that the surface
of levitated droplets facilitate the oxidation of methyl thioglycolate in the
dark, while illumination is necessary to produce the oxidation in bulk
experiments.
PMID- 29947625
TI - Nucleation of protein crystals - a nanoscopic perspective.
AB - Macromolecular phase transitions bear great medical, scientific and industrial
relevance, yet the molecular picture of their earliest beginnings is still far
from complete. For decades, progress has been hampered by the challenges
associated with studying stochastic nucleation phenomena occurring on nanoscopic
length scales. In the last 5 years, however, the field has advanced with great
strides due to the recent buildout of experimental techniques that allow us to
observe details of the nucleation process on the nanoscale. In this review, we
present a historical overview and state-of-the-art analysis of protein crystal
nucleation from an experimentalist's perspective. After a short introduction of
key concepts from classical nucleation theory, we discuss the advancements that
have led to the development of alternative models of protein nucleation. We
summarize the experimental proof in favour of these various models, but we also
focus on some of their shortcomings and experimental blind spots. In our
penultimate section we highlight recent works that have provided direct
nanoscopic insight into the nucleation of protein crystals. We end with
concluding paragraphs discussing outstanding questions and possible strategies to
advance the field further in the future.
PMID- 29947626
TI - Perfluorocarbon-loaded polydopamine nanoparticles as ultrasound contrast agents.
AB - A versatile platform for the development of new ultrasound contrast agents is
demonstrated through a one-pot synthesis and fluorination of submicron
polydopamine (PDA-F) nanoparticles. The fluorophilicity of these particles allows
loading with perfluoropentane (PFP) droplets that display strong and persistent
ultrasound contrast in aqueous suspension and ex vivo tissue samples. Contrast
under continuous imaging by color Doppler persists for 1 h in 135 nm PDA-F
samples, even at maximum clinical imaging power (MI = 1.9). Additionally, use of
a Cadence Contrast Pulse Sequence (CPS) results in a non-linear response suitable
for imaging at 0.5 mg mL-1. Despite the PFP volatility and the lack of a hollow
core, PDA-F particles display minimal signal loss after storage for over a week.
The ability to tune size, metal-chelation, and add covalently-bound organic
functionality offers myriad possibilities for extending this work to multimodal
imaging, targeted delivery, and therapeutic functionality.
PMID- 29947627
TI - Multifunctional mixed valence N-doped CNT@MFe2O4 hybrid nanomaterials: from
engineered one-pot coprecipitation to application in energy storage paper
supercapacitors.
AB - This work reports on the design of novel mixed valence hybrid N-doped carbon
nanotubes/metal ferrite nanomaterials (MFe2O4, M(ii) = Mn, Fe, Co) with tailored
composition, and magnetic and electrical properties through a straightforward eco
sustainable and less time consuming one-pot in situ coprecipitation process. The
potentialities of this strategy rely on the lack of oxidative treatments to the
support and thermal annealing, besides the use of aqueous conditions, a chelating
base (isopropanolamine) and low temperatures. The process afforded the controlled
nucleation/growth of the MFe2O4 nanoparticles (NPs), with sizes of 3.2-5.4 nm and
superparamagnetic properties, on the surface of the N-doped carbon nanotubes (CNT
N) and their immobilization by covalent bonding. The nitrogen-based
functionalities of CNT-N allied with the use of a coprecipitation agent with
coordinating properties towards M(ii)/Fe(iii) cations were responsible for these
achievements. To unravel the potentialities of the novel nanohybrids (CNT-N@M),
they were tested as electrode active nanomaterials in the fabrication of all
solid-state asymmetric paper supercapacitors (SCs). All asymmetric SCs presented
significantly higher performance than the symmetric CNT-N based one, with an
enhancement of the energy density to up to 6.0* and of the power density to up to
4.3* due to the occurrence of both non-faradaic and faradaic charge storage
mechanisms. Moreover, they led to enhanced volumetric energy density (up to
11.1*) and power density (up to 5.2*) compared with other solid-state hybrid
paper SCs based on carbon materials recently reported in the literature. These
results highlight the importance of conjugating a conductive support bearing N
based functionalities with MFe2O4 NPs featuring redox properties towards
synergistically enhanced energy storage.
PMID- 29947628
TI - Insertion of CS2 into the Mg-H bond: synthesis and structural characterization of
the magnesium dithioformate complex, [TismPriBenz]Mg(kappa2-S2CH).
AB - The tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl]methyl magnesium hydride
compound, [TismPriBenz]MgH, undergoes insertion of CS2 into the Mg-H bond at room
temperature to give [TismPriBenz]Mg(kappa2-S2CH), the first structurally
characterized magnesium dithioformate compound. The dithioformate complex
[TismPriBenz]Mg(kappa2-S2CH) reacts with (i) CO2 at 80 degrees C to give, inter
alia, the formate counterpart, [TismPriBenz]Mg(kappa2-O2CH), and (ii) Me3SiX (X =
Cl, Br), Me3SnX (X = F, Cl, Br) and MeI to afford the halide derivatives,
[TismPriBenz]MgX.
PMID- 29947629
TI - Prediction of the binding mode and resistance profile for a dual-target pyrrolyl
diketo acid scaffold against HIV-1 integrase and reverse-transcriptase-associated
ribonuclease H.
AB - The rapid emergence of drug-resistant variants is one of the most common causes
of highly active antiretroviral therapeutic (HAART) failure in patients infected
with HIV-1. Compared with the existing HAART, the recently developed pyrrolyl
diketo acid scaffold targeting both HIV-1 integrase (IN) and reverse
transcriptase-associated ribonuclease H (RNase H) is an efficient approach to
counteract the failure of anti-HIV treatment due to drug resistance. However, the
binding mode and potential resistance profile of these inhibitors with important
mechanistic principles remain poorly understood. To address this issue, an
integrated computational method was employed to investigate the binding mode of
inhibitor JMC6F with HIV-1 IN and RNase H. By using per-residue binding free
energy decomposition analysis, the following residues: Asp64, Thr66, Leu68,
Asp116, Tyr143, Gln148 and Glu152 in IN, Asp443, Glu478, Trp536, Lys541 and
Asp549 in RNase H were identified as key residues for JMC6F binding. And then
computational alanine scanning was carried to further verify the key residues.
Moreover, the resistance profile of the currently known major mutations in HIV-1
IN and 2 mutations in RNase H against JMC6F was predicted by in silico
mutagenesis studies. The results demonstrated that only three mutations in HIV-1
IN (Y143C, Q148R and N155H) and two mutations in HIV-1 RNase H (Y501R and Y501W)
resulted in a reduction of JMC6F potency, thus indicating their potential role in
providing resistance to JMC6F. These data provided important insights into the
binding mode and resistance profile of the inhibitors with a pyrrolyl diketo acid
scaffold in HIV-1 IN and RNase H, which would be helpful for the development of
more effective dual HIV-1 IN and RNase H inhibitors.
PMID- 29947630
TI - Correction: Neutron diffraction studies on the thermal expansion and anomalous
mechanics in the perovskite-type [C(ND2)3]Me2+(DCOO)3 [Me = Cu, Mn, Co].
AB - Correction for 'Neutron diffraction studies on the thermal expansion and
anomalous mechanics in the perovskite-type [C(ND2)3]Me2+(DCOO)3 [Me = Cu, Mn,
Co]' by M. Viswanathan et al., Phys. Chem. Chem. Phys., 2018, DOI:
10.1039/c8cp01245h.
PMID- 29947631
TI - One-step synthesis of cyclic compounds towards easy room-temperature
phosphorescence and deep blue thermally activated delayed fluorescence.
AB - With the advantages of facile one-pot synthesis and THF-irrigating purification,
we first developed novel cyclic compounds with deep blue thermally activated
delayed fluorescence (TADF) and room-temperature phosphorescence (RTP) dual
emission even in the as-spun films. Careful crystal analysis, combined with
theoretical calculations, reveal that abundant inter- and intra-molecular
interactions, whatsoever the molecular packing, are obligated to unique RTP
properties. These results open up a new study of compounds with multiple
acceptors and donors, and represent an important step in the further development
of deep blue TADF and easy RTP emission.
PMID- 29947632
TI - Unsupported metal silyl ether coordination.
AB - Simple silyl ethers like O(SiMe3)2 in contrast to normal ethers are inert to
metal bonding; however, a "naked", highly Lewis-acidic, cationic Mg species
enforces complexation. DFT calculations indicate that agostic interactions and
van der Waals attraction significantly contribute to the stability of this first
example of unsupported metal silyl ether coordination.
PMID- 29947633
TI - UV-visible photocurrent enhancement using metal-semiconductor-metal with
symmetric and asymmetric double Schottky barriers.
AB - We experimentally report improved photocurrent performance under the illumination
of both UV and visible light in the metal-semiconductor-metal nanostructures with
double Schottky barriers, consisting of a monolayer of Au nanoparticles and a
planar Au film separated by a thin WO3 layer. In addition to the near-unit
broadband optical absorption causing the increased population of hot electrons,
we demonstrate that the occurrence of the electron trapping effect at the bottom
Schottky barrier is also responsible for the photocurrent enhancement under
visible light illumination. Under the direct UV bandgap excitation of WO3, the
electron trapping effect at the bottom barrier plays a crucial role in the anodic
photocurrent enhancement. Furthermore, we demonstrate that by replacing the Au
film with the metal Pt of higher work function to increase the barrier height of
the bottom Schottky barrier, and hence strengthening its ability for electron
trapping, the photocurrent is found to gain a further significant enhancement
under the illumination of both visible and UV light.
PMID- 29947634
TI - Dibenzofuran-4,6-bis(oxazoline) (DBFOX). A novel trans-chelating bis(oxazoline)
ligand for asymmetric reactions.
AB - The trans-chelating bis(oxazoline) ligand (R,R)-4,6-dibenzofurandiyl-2,2'-bis(4
phenyloxazoline) [(R,R)-DBFOX/Ph] coordinates metal ions to give C2-symmetric
complexes which effectively catalyze a variety of asymmetric reactions. (R,R)
DBFOX/Ph.Ni(ClO4)2.3H2O, whose crystal structure is octahedral with three aqua
ligands, can be stored under air for several months without loss of catalytic
activity and promotes highly enantioselective reactions even in the presence of
excess amounts of water, alcohols, amines, and acids. The complex shows
remarkable chiral amplification in asymmetric Diels-Alder (DA) reactions. This
review focuses on enantioselective reactions catalyzed by (R,R)-DBFOX/Ph.metal
complexes.
PMID- 29947635
TI - Remote activation and detection of up-converted luminescence via surface plasmon
polaritons propagating in a silver nanowire.
AB - In this paper, we demonstrate remote activation and detection of the 2-photon up
conversion luminescence via surface plasmon polaritons propagating in a long
silver nanowire. The hybrid nanostructure was assembled by locally depositing a
submicron droplet of nanocrystal-containing colloidal solution on one of the ends
of the metallic nanowire. When - using a classic confocal microscope - the second
end of the nanowire, without the nanocrystals, is illuminated with infrared laser
light, we observe strong emission from the same end. Therefore, it indicates that
surface plasmon polaritons activated with infrared light at the second end of the
nanowire propagate along it and can excite nanocrystals in the droplet at the
opposite end. Subsequently, the excited nanocrystals up-convert the energy and by
launching surface plasmon polaritons can guide the up-converted luminescence back
to the starting point. The emergence of this effect is much more pronounced for a
laser polarized along the nanowire. The spectral and temporal character of this
emission reveals strong interactions between surface plasmon polaritons and
electronic states of the nanocrystals. The details of local and non-local aspects
of the effects of remote excitation and guiding of energy in a silver nanowire
are elucidated using a unique experimental setup, based on two microscope
objectives for spatial separation and control of both excitation and emission
beams.
PMID- 29947636
TI - Emergent magnetoelectricity in soft materials, instability, and wireless energy
harvesting.
AB - Magnetoelectric materials that convert magnetic fields into electricity and vice
versa are rare and usually complex, hard crystalline alloys. Recent work has
shown that soft, highly deformable magnetoelectric materials may be created by
using a strain-mediated mechanism. The electromagnetic and elastic deformation of
such materials is intricately coupled, giving rise to a rather rich instability
and bifurcation behavior that may limit or otherwise put bounds on the emergent
magnetoelectric behavior. In this work, we investigate the magneto-electro
mechanical instability of a soft dielectric film subject to mechanical forces and
external electric and magnetic fields. We explore the interplay between
mechanical strain, electric voltage and magnetic fields and their impact on the
maximum voltage and the stretch the dielectric material can reach. Specifically,
we present physical insights to support the prospects to achieve wireless energy
harvesting through remotely applied magnetic fields.
PMID- 29947642
TI - Pharmacotherapeutic follow-up in a respiratory intensive care unit: description
and analysis of results.
AB - OBJECTIVE: To describe and evaluate the pharmacotherapeutic follow-up by a
clinical pharmacist in an intensive care unit. METHODS: A descriptive and cross
sectional study carried out from August to October 2016. The data were collected
through a form, and pharmacotherapeutic follow-up conducted by a clinical
pharmacist at the respiratory intensive care unit of a tertiary hospital. The
problems recorded in the prescriptions were quantified, classified and evaluated
according to severity; the recommendations made by the pharmacist were analyzed
considering the impact on pharmacotherapy. The medications involved in the
problems were classified according to the Anatomical Therapeutic Chemical
Classification System. RESULTS: Forty-six patients were followed up and 192
pharmacotherapy-related problems were registered. The most prevalent problems
were missing information on the prescription (33.16%), and those with minor
severity (37.5%). Of the recommendations made to optimize pharmacotherapy, 92.7%
were accepted, particularly those on inclusion of infusion time (16.67%), and
dose appropriateness (13.02%), with greater impact on toxicity (53.6%).
Antimicrobials, in general, for systemic use were drug class most often related
to problems in pharmacotherapy (53%). CONCLUSION: Pharmacotherapeutic follow-up
conducted by a pharmacist in a respiratory intensive care unit was able to detect
problems in drug therapy and to make clinically relevant recommendations.
PMID- 29947643
TI - Evaluation of quality of sleep in women with stress urinary incontinence before
and after surgical correction.
AB - OBJECTIVE: To evaluate the quality of sleep in women with urinary incontinence
before and after sling surgery. METHODS: A prospective study of case series of
women with urodynamic diagnosis of stress urinary incontinence. To evaluate the
subjective quality of sleep, two specific questionnaires were used and validated
for the Portuguese Language: Epworth Sleepiness Scale and Pittsburgh Sleep
Quality Index. The questionnaires were applied before and 6 months after surgical
repair. RESULTS: When analyzing the Epworth Sleepiness Scale, there was an
improvement in sleep quality (p=0.0401). For the Pittsburgh Sleep Quality Index,
only for sleep disorder there was improvement in quality of sleep after surgery
(p=0.0127). CONCLUSION: Women with urinary incontinence, submitted to surgery
with sling, showed improvement in both quality of sleep and sleep disorder.
PMID- 29947644
TI - People management: from the intuitive process to People Analytics.
PMID- 29947645
TI - Immunotherapy-induced pneumonitis: cases report.
AB - Immunotherapy-induced pneumonitis is a rare complication with incidence estimated
around 3%. This disease is difficult to diagnose and has great morbidity. For
this reason, it became a challenge for oncologists and emergencists. We reviewed
the case of five patients who used anti-PD1 (program cell death receptor
antagonist 1) for antineoplastic treatment and developed treatment-induced
pneumonitis. All patients had respiratory problems because of immunotherapy and
presence of ground-glass radiologic change. Among all patients, only one had
grade 5 pneumonitis, and delaying to begin corticosteroid therapy and worsening
in clinical picture led to patient death. Other four patients with symptomatic
grade 2 pneumonitis underwent corticosteroid therapy and had improvement in
clinical and radiologic picture. Two patients were treated after an episode of
pneumonitis, and no new pulmonary complications were observed until the end of
this study. Immunotherapy-induced pneumonitis, although uncommon, can be
potentially fatal. Medical team has the responsibility to pay attention for most
common symptoms of the disease such as cough and dyspnea and conduct an early
diagnosis and effective early treatment with corticosteroids.
PMID- 29947646
TI - Preference of red mite Tetranychus ludeni Zacher (Acari: Tetranychidae) to sweet
potato genotypes.
AB - Tetranychus ludeni damages the sweet potato. Pest development can vary between
plant genotypes. The objective was to identify the preference of Tetranychus
ludeni for Ipomoea batatas genotypes, from the germplasm bank at the Universidade
Federal dos Vales do Jequitinhonha e Mucuri (UFVJM). Natural infestations of this
mite were observed on 54 sweet potato genotypes in potted, in a greenhouse. Three
mite-infested leafs of each genotype were collected and analyzed. The red mite
showed different population density rate in genotypes. The BD 29 genotype was
found to be highly susceptible, the BD 08, BD 57, BD 17 and Espanhola genotypes
were moderately susceptible, and the others forty-nine genotypes showed low
susceptibility to the mite.
PMID- 29947647
TI - Primary umbilical endometriosis.
AB - OBJECTIVE: to report the characteristics, evolution and outcome of patients with
primary umbilical endometriosis. METHODS: an observational and descriptive study
of patients with primary umbilical endometriosis diagnosed between 2014 and 2017.
The clinical variables evaluated were age, clinical picture, lesion
characteristics, diagnostic methods, treatment and recurrence. RESULTS: six
patients diagnosed with primary umbilical endometriosis aged 28 to 45 years were
operated on during the study period. They had lesions ranging from one to 2.5cm
in diameter, violet in five patients and erythematous-violaceous in one. The
duration of the symptoms until diagnosis ranged from one to three years and in
all the cases studied the diagnosis was made through the clinical manifestations
and confirmed by histopathological analysis. No case was associated with
neoplastic alterations. All patients evaluated had pain and umbilical bleeding in
the menstrual period. CONCLUSION: umbilical endometriosis is an uncommon disease
and should be included in the differential diagnosis of women as umbilical
nodules. The treatment of choice is the total exeresis of the lesion.
PMID- 29947648
TI - Evaluation of nicotine patch in pain control of patients undergoing laparoscopic
cholecystectomy.
AB - OBJECTIVE: to analyze the effects of nicotine patch on pain control, occurrence
of nausea and its hemodynamic repercussions in laparoscopic cholecystectomy
procedures. METHODS: we conducted an analytical, prospective, randomized, triple
blinded, clinical study between January and July 2017. The sample consisted of 17
patients who underwent laparoscopic cholecystectomy for the treatment of
cholelithiasis. Nine patients used nicotine patch, and eight, placebo patch. The
studied variables were pain, nausea, patient satisfaction, blood pressure, heart
rate, oximetry and morphine rescue. RESULTS: taking into account the pain and
nausea parameters, there was no statistically significant difference between the
groups (p>0.05). Also, the evaluation of rescue medication, both opioids and
prokinetics, did not show any significant statistical difference between the
groups. Among the hemodynamic parameters, there was only one statistically
significant difference in the analysis of oxygen saturation and systolic blood
pressure (SBP) six hours after surgery: the mean oxygen saturation was higher in
the Test group (97.89 x 95.88) and the mean SBP was higher in the Control group
(123.89 x 110.0). CONCLUSION: although pain levels were lower for nicotine within
24 hours, the action of nicotine and the need for rescue opioids in pain control
were not statistically significant between the groups and at the time intervals
studied. There was no clinical repercussion in the hemodynamic parameters.
PMID- 29947649
TI - Mycotic aneurysm due to Salmonella species: clinical experiences and review of
the literature.
AB - The mortality of patients with mycotic aneurysms is high, especially in East
Asia, and infection by Salmonella species is the most common. Our study aimed to
improve prognosis of adult mycotic aneurysms with early diagnosis and accurate
treatment. Four adult patients with mycotic aneurysm caused by Salmonella were
included and analyzed by single-center retrospective analysis. Cases reported in
the literature during the past 10 years were also summarized. The average age of
the 4 male patients was 61.25 years, while that of the 53 cases reported in the
literature was 65.13 years. Hypertension, diabetes, and atherosclerosis were
common complications. Most patients presented fever and experienced pain at the
corresponding position of the aneurysm. Laboratory examination found an increased
number of white blood cells accompanied by an increase in inflammatory markers.
Most aneurysms were found in the abdominal aorta, while the rupture of an
aneurysm was the most common complication. The mortality rates were 21.43 and
7.14% after open surgery or endovascular aneurysm repair (EVAR) intervention,
respectively. The recurrence rates of infection were 0 and 17.85% for both
treatments, respectively. The mortality rate of mycotic aneurysm caused by
Salmonella infection was high in middle-aged males with hypertension, diabetes,
and atherosclerosis. The possibility of a Salmonella-infected aneurysm should be
considered in these high-risk groups presenting chills, fever, chest, and back
pain. Open surgery was superior to EVAR treatment in the clearance of infected
foci and the reduction of postoperative recurrence. The recurrence of
postoperative infection can be prevented by intravenous antibiotic therapy for 6
weeks post-surgery.
PMID- 29947650
TI - Study of major genetic factors involved in pituitary tumorigenesis and their
impact on clinical and biological characteristics of sporadic somatotropinomas
and non-functioning pituitary adenomas.
AB - Genetic and functional aberrations of guanine nucleotide-binding protein, alpha
stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and
pituitary tumor transforming gene (PTTG) are among the most prominent events in
pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas
(n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary
referral center were evaluated for GNAS and AIP mutations and gene expression of
AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53
expression) characteristics of tumors and their response to therapy, if
applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of
NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in
clinical characteristics, tumor extension, response to somatostatin analog
therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression
between mutated and non-mutated somatotropinomas patients. PTTG overexpression
(RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56,
min=0.46-max=0.92) were found in virtually all cases without a statistically
significant relationship with clinical and biological tumor features. No patients
exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations
in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and
treatment outcomes in this cohort. Our data support some previous studies and
point to the need for further investigations, probably involving epigenetic and
transcriptome analysis, to improve our understanding of pituitary tumor behavior.
PMID- 29947651
TI - Meglumine antimoniate intralesional infiltration for localised cutaneous
leishmaniasis: a single arm, open label, phase II clinical trial.
AB - BACKGROUND: Cutaneous leishmaniasis (CL) is a world-wide health problem which
currently lacks effective, affordable and easy to use therapy. Recently, the
meglumine antimoniate (MA) intralesional infiltration was included among the
acceptable therapies for New World leishmaniasis. While this approach is
attractive, there is currently little evidence to support its use in Americas.
OBJECTIVES: The aim of this study was to provide information about effectiveness
and safety of a standardised MA intralesional infiltration technique for the
treatment of CL. METHODS: It is a single-arm phase II clinical trial conducted at
a Brazilian referral centre. CL cases with parasitological confirmation
presenting a maximum of three CL-compatible skin lesions were treated with weekly
MA intralesional infiltration by using a validated technique, up to a maximum of
eight infiltrations. RESULTS: A total of 53 patients (62 lesions) were included.
Overall, patients received a median of seven infiltrations (IQR25-75% 5-8) over a
median treatment period of 43 days (IQR25-75% 28-52 days). The definitive cure
rate at D180 was 87% (95% CI:77-96%). The majority of adverse events were local,
with mild or moderate intensity. Bacterial secondary infection of the lesion site
was observed in 13% of the treated patients, beside two intensity-three adverse
events (hypersensitivity reactions).
PMID- 29947652
TI - Weight-teasing: does body dissatisfaction mediate weight-control behaviors of
Brazilian adolescent girls from low-income communities?
AB - The objective was to examine the mediation hypothesis of body dissatisfaction and
analyze their association with weight-teasing and body satisfaction. A total of
253 girls who attended 10 schools from Sao Paulo, Brazil, participated in this
study. Data collection was carried out through a validated and self-reported
questionnaire. Study variables were weight-teasing (independent), body
satisfaction (mediation), and weight control behavior (outcome). Effect mediation
analyses showed a significance level of 5% (p < 0.05). Prevalence of family and
peers weight-teasing were 38.5% and 40.6%, respectively. Body dissatisfaction was
associated with unhealthy weight control behaviors when controlled by family and
peer weight-teasing. Data indicate that family and peers teasing are important
aspects that interfere in body satisfaction and weight control behaviors.
PMID- 29947653
TI - Sustainable Development Goals and tuberculosis in Brazil: challenges and
potentialities.
PMID- 29947654
TI - Guidelines for early detection of breast cancer in Brazil. II - New national
recommendations, main evidence, and controversies.
AB - Breast cancer is the leading cause of cancer mortality in Brazilian women. The
new Brazilian guidelines for early detection of breast cancer were drafted on the
basis of systematic literature reviews on the possible harms and benefits of
various early detection strategies. This article aims to present the
recommendations and update the summary of evidence, discussing the main
controversies. Breast cancer screening recommendations (in asymptomatic women)
were: (i) strong recommendation against mammogram screening in women under 50
years of age; (ii) weak recommendation for mammogram screening in women 50 to 69
years of age; (iii) weak recommendation against mammogram screening in women 70
to 74 years of age; (iv) strong recommendation against mammogram screening in
women 75 years or older; (v) strong recommendation that screening in the
recommended age brackets should be every two years as opposed to shorter
intervals; (vi) weak recommendation against teaching breast self-examination as
screening; (vii) absence of recommendation for or against screening with clinical
breast examination; and (viii) strong recommendation against screening with
magnetic resonance imaging, ultrasonography, thermography, or tomosynthesis alone
or as a complement to mammography. The recommendations for early diagnosis of
breast cancer (in women with suspicious signs or symptoms) were: (i) weak
recommendation for the implementation of awareness-raising strategies for early
diagnosis of breast cancer; (ii) weak recommendation for use of selected signs
and symptoms in the current guidelines as the criterion for urgent referral to
specialized breast diagnosis services; and (iii) weak recommendation that every
breast cancer diagnostic workup after the identification of suspicious signs and
symptoms in primary care should be done in the same referral center.
PMID- 29947655
TI - [Inclusion of a deterministic post-processing stage to increase the performance
of probabilistic record linkage].
AB - The aim of this study was to demonstrate the application of a deterministic post
processing stage, based on measures of similarity, to increase the performance of
probabilistic record linkage with and without manual revision. The databases used
in the study were the Brazilian Information System for Notificable Diseases and
the Brazilian Mortality Information System, from 2007 to 2015, in Palmas,
Tocantins State, Brazil. The probabilistic software was OpenRecLink, and a
deterministic post-processing stage was applied to the data obtained from three
different probabilistic linkage strategies. The three strategies were compared to
each other, and the deterministic post-processing stage was added. The
sensibility of the probabilistic strategies without manual revision varied from
69.1% and 77.8%, while the same strategies plus the deterministic post-processing
stage varied from 92.9% to 96.3%. Sensitivity of the two probabilistic strategies
with manual revision was similar to that obtained by the deterministic post
processing stage, but the number of matches that were referred to manual revision
by the two probabilistic strategies varied between 1,177 and 1,132 records,
compared to 149 and 145 after the deterministic post-processing stage. Our
findings suggest that the deterministic post-processing stage is a promising
option, both to increase the sensitivity and to reduce the number of matches that
need to be reviewed manually, or even to eliminate the need for manual revision
altogether.
PMID- 29947656
TI - Changes in life expectancy due to avoidable and non-avoidable deaths in
Argentina, Chile, Colombia and Mexico, 2000-2011.
AB - The objective of this study was to analyze the level and trend of avoidable
deaths and non-avoidable deaths and their contribution to the change in life
expectancy in Latin America by studying the situations in Argentina, Chile,
Colombia and Mexico between the years 2000 and 2011, stratified by sex and 5-year
age groups. The information source used in this study was the mortality vital
statistics, and the population data were obtained from censuses or estimates. The
proposal by Nolte & McKee (2012) was used to calculate the standardized mortality
rates and the influence from avoidable and non-avoidable causes in the change in
life expectancy between 0 and 74 years. In Argentina, Chile and Colombia, all the
rates declined between the years 2000 and 2011, whereas in Mexico, the avoidable
deaths and non-avoidable deaths rates increased slightly for men and decreased
for women. In all the countries, the non-avoidable death rates were higher than
the avoidable death rates, and the rates were higher for men. The largest
contributions to changes in life expectancy were explained by the non-avoidable
deaths for men in all countries and for women in Argentina; in contrast, in
Chile, Colombia and Mexico, the gains in years of life expectancy for women were
mainly a result of avoidable causes. The results suggest there have been
reductions in mortality from these causes that have resulted in gains in years of
life expectancy in the region. Despite these achievements, differences between
countries, sex and age groups are still present, without any noticeable progress
in the reduction of these inequalities until now.
PMID- 29947657
TI - [From recommendations to practice: eight years of challenges for children's
health in primary care services in the interior of Sao Paulo State, Brazil].
AB - This article aims to identify changes in indicators for the organization of
children's health services in primary care in the State of Sao Paulo, Brazil. An
evaluative study was conducted with three series of cross-sectional evaluations
with participation by 81 services, involving 32 municipalities (counties) in the
central-west region of the state, who answered the Quali AB questionnaire in
2007, 2010, and 2014. The analysis used 74 children's health indicators and 7
services indicators. Comparison of the indicators evidenced changes in the
organization of children's healthcare, with an improvement in the majority of the
indicators in 2010 and maintenance or worsening in 2014, compared to 2007. In
conclusion, children's health policy recommendations have not been fully realized
in the organization of the supply of comprehensive care, although relevant issues
such as childhood obesity and violence have been addressed by a few services.
PMID- 29947658
TI - Breast cancer control policies in Brazil: where to go from here?
PMID- 29947659
TI - On health needs: the concept labyrinth.
AB - This study aims to reflect on the intertwining of certain key ideas about what we
call "health" within the hegemonic biomedical paradigm: health, disease, health
needs, medicalization and medical-industrial complex. This reflection is based on
the philosophical contributions of Heller and Wiggins on needs; on the discussion
of some authors, especially Canguilhem, about health and illness; and Collins'
sociology of expertise. After pointing out some of the conundrums that arise from
the conceptual fluidity of the topics abovementioned, we present a path forward,
based on Collins' proposals about the role of experts in political arguments, to
resituate the discussion on health needs.
PMID- 29947660
TI - Guidelines for early detection of breast cancer in Brazil. I - Development
methods.
AB - Clinical guidelines are traditionally drafted by expert consensus. The benefits
of mammographic screening have been questioned in recent years, owing to biases
detected in the clinical trials that popularized its widespread use. Meanwhile,
growing body of evidence on harms associated with mammographic screening also
required a new approach, taking into account the uncertainties on the benefits
and a balance between the gains and possible harms from screening. This article
discusses the development of the new guidelines for early detection of breast
cancer in Brazil, with details on the drafting methods and implications for the
new recommendations. The new methodology features systematic literature reviews,
assessment of the validity of the evidence, and the balance between each
intervention's risks and benefits, ensuring greater transparency,
reproducibility, and validity in the drafting process. The new guidelines also
include recommendations for cases with suspicious signs and symptoms. The authors
provide a detailed discussion of the advantages of the approach as compared to
the traditional expert consensus model, as well as the methods' limitations and
disadvantages. They also address the implications of various decisions, such as
choices on study designs, screening effectiveness outcomes, definition of
overdiagnosis, and methods for calculation.
PMID- 29947661
TI - [Differences in live birth clusters in the city of Sao Paulo, Brazil, 2010].
AB - This study aimed to identify birth clusters according to type of hospital (SUS
vs. non-SUS) and the existence of differences in socioeconomic, maternal,
neonatal, and healthcare access characteristics, measured by the distance between
the mothers' homes and the hospitals where they gave birth. Births to mothers
residing in the city of Sao Paulo, Brazil, in 2010 were georeferenced and
allocated in 310 weighting areas from the population census, in addition to
classifying them according to hospital of birth (SUS vs. non-SUS). Spatial
clusters were identified through the spatial sweep technique for spatial
dependence of SUS and non-SUS births, leading to the formation of ten SUS
clusters and seven non-SUS clusters. Births in non-SUS hospitals formed clusters
in the city's central area, with a lower proportion of low-income households. The
SUS birth clusters were located on the outskirts of the city, where there are
more households in subnormal clusters. Both SUS and non-SUS clusters were not
internally homogeneous, showing differences in maternal age, schooling, and
number of prenatal visits and very premature newborns. The theoretical mean
distance traveled by mothers to the hospital was 51.8% lower in the SUS clusters
(5.1km) than in the non-SUS clusters (9.8km). The formation of birth clusters
showed differences in maternal, pregnancy, childbirth, and neonatal
characteristics, in addition to displaying a radial-concentric spatial
distribution, reflecting the city's prevailing socioeconomic differences. The
shorter distance in SUS births indicates regionalization of childbirth care in
the city of Sao Paulo.
PMID- 29947662
TI - [Inequality in access to health services between urban and rural areas in Brazil:
a disaggregation of factors from 1998 to 2008].
AB - Access to healthcare is an important dimension of inequalities between urban and
rural areas. Access is lower in rural areas due to the population's greater
social vulnerability and greater difficulties in access among its social groups.
Based on data from the health supplement of the Brazilian National Household
Sample Survey, we analyzed the determinants of access and differences between
urban and rural areas from 1998 to 2008. The analysis of determinants of access
to health services used binary logistic regression. Differences between urban and
rural areas were disaggregated as observable factors (enabling, need, and
predisposing) and non-observable factors (supply and difficulty in access). The
results highlight that inequality in access is higher in rural areas. Need
factors are fundamental determinants of access to health, while enabling factor
are more important for explaining the differences between urban and rural areas.
The slight reduction in differences during the period was due mainly to changes
in the rural population's composition.
PMID- 29947663
TI - Growth of the Anchovy Anchoa tricolor in a brazilian subtropical estuary.
AB - This study aimed to describe the growth parameters of Anchoa tricolor in a
subtropical estuary. From August 2010 to July 2011, 10.009 specimens of the
anchovy Anchoa tricolor, mean total length 4.2 cm (+/-1.45), were captured in the
intertidal region of the Estuarine Complex of Paranagua (25o 15' - 25 degrees
35' S and 48 degrees 20' - 48 degrees 45' W). Species's weight/length
relationship for grouped genders was described as follow: W = 0.0000591.Lt3.282
(length in centimeters; weight in grams) showing a positive allometric growth
pattern (b>3; P=0.000). Significant differences concerning weight/length
relationship for males, females and unsexed individuals were identified.
Parameters of the length to age growth curve were estimated by adjusting a von
Bertalanffy growth equation from aged individuals from a length-frequency
distribution: Linfinity = 10.06 (1-e-17715(t + 0.205)) (length in centimeters,
age in years). The age to attain 95% of the asymptotic length ( A95 ; longevity
sensu Taylor) was estimated at 1.7 years. Size frequency distributions indicate
that A. tricolor uses the estuarine area as reproductive and growing grounds,
especially during the first year of the life cycle, where the species represent a
key element for ecosystem functioning due to relatively high abundance and energy
transference from plankton to top predators.
PMID- 29947664
TI - Treatment with either leflunomide or adalimumab reduces anaemia in patients with
rheumatoid arthritis.
AB - Rheumatoid arthritis is a chronic disease of the joints, which causes joint pain
and disability. Anaemia is a frequent extra-articular manifestation in rheumatoid
arthritis, affecting 30-70% of the patients; presenting a negative impact on
patient's quality of life. Some of the drugs used in rheumatoid arthritis
treatment improve anaemia; but little is known on the beneficial effects of the
anti-rheumatic leflunomide or the anti-TNFalpha adalimumab, in this parameter. We
investigated the incidence of anaemia in rheumatoid arthritis patients treated or
not with leflunomide or adalimumab. We also assessed whether anaemia correlates
with disease activity. Anaemia was present in patients who had just been
diagnosed with rheumatoid arthritis and had never taken disease modifying agents
or biologicals (non-specific therapy group), but not in those taking either
leflunomide or adalimumab. The erythrocyte sedimentation rate was increased in
patients with non-specific therapy in comparison with those taking either
leflunomide or adalimumab. Anaemia correlated with increased erythrocyte
sedimentation rate. We suggest that leflunomide and adalimumab may be useful in
treating anaemia in patients with rheumatoid arthritis.
PMID- 29947665
TI - Geographic and Gender Diversity in the Brazilian Academy of Sciences.
AB - Recent studies have shown that diversity in race and gender is important to
improve competitiveness, creativity and innovation. However, many studies have
shown that the universe of science is not diverse in none of these criteria. In
this work, we quantify the gender and geographic diversity in the Brazilian
science. We study in detail the profile of the titular members of the most
prestigious academic institution of Brazil, the Brazilian Academy of Sciences
(ABC). Our analysis shows that the members of the ABC concentrates 80% in the
Southeast region and that the overwhelming majority is composed by men. We show
that female and male researchers have roughly the same amount of publication per
year but women produce more human resources. Using the Brazilian Researchers'
Fellowship databank we show that the gender and diversity both in gender and in
geography decreases along the researchers' career.
PMID- 29947666
TI - Conformational analysis of Pneumococcal Surface Antigen A (PsaA) upon zinc
binding by fluorescence spectroscopy.
AB - PsaA (pneumococcal surface antigen A) is a S. pneumoniae virulence factor that
belongs to the metal transport system. The Manganese PsaA binding has been
associated with oxidative stress resistance becoming a pivotal element in the
bacteria virulence. It has been shown that Zinc inhibits the Manganese
acquisition and promotes bacteria toxicity. We have performed a PsaA
conformational analysis both in the presence (Zn-rPsaA) and in the absence of
Zinc (free-rPsaA). We performed experiments in the presence of different Zinc
concentrations to determine the metal minimum concentration which induced a
conformational change. The protein in free and Zn-binding condition was also
studied in pH ranging 2.6-8.0 and in temperature ranging 25oC-85oC. pH
experiments showed a decrease of fluorescence intensity only in acidic medium.
Analysis of the heat-induced denaturation demonstrated that Zinc-binding promoted
an increase in melting temperature from 55oC (free-rPsaA) to 78.8oC (Zn-rPsaA)
according to fluorescence measurements. In addition, the rPsaA stabilization by
Zinc was verified through analysis of urea and guanidine hydrochloride
denaturation. Data showed that Zinc promoted an increase in the rPsaA stability
and its removal by EDTA can lead to a PsaA intermediate conformation. These
findings can be considered in the development of vaccines containing PsaA as
antigen.
PMID- 29947667
TI - Development of an indirect ELISA assay to evaluation of the adaptive immune
response of pacu (Piaractus mesopotamicus).
AB - The pacu is one of the most important species for Brazilian fish farming and is
considered emerging in the global aquaculture. Despite its importance, no
effective tool for evaluation of the adaptive immune response of this species has
been developed. Therefore, this study aimed the development and standardization
of indirect ELISA for the measurement of pacu antigen-specific antibodies using
polyclonal rabbit anti-pacu IgM used as detector antibody. For this purpose was
isolated and purificated of pacu IgM using mannose-binding protein affinity
chromatography and produced specific polyclonal antibodies against heavy and
light chains pacu IgM, that showed a molecular weight of 72 kDa and 26 kDa,
respectively. Polyclonal antibodies obtained demonstrated specificity with heavy
and light Ig chains of pacu serum in western blotting. These polyclonal
antibodies allowed the development of an indirect ELISA assay of high sensitivity
and specificity for the detection and quantification of pacu IgM antibodies
immunized with bovine IgG. In conclusion, this approach has great potential to
improve the monitoring of vaccine-induced immune responses and help develop
immunodiagnostic and epidemiological studies of infectious diseases in pacu
systems.
PMID- 29947668
TI - Acetylcholinesterase inhibition and antimicrobial activity of hydroxyl amides
synthesized from natural products derivatives.
AB - Thirteen natural products derivatives of hydroxyl amide class, three described
for the first time, were synthesized by reaction of three indole acids and 3,4,5
trimethoxybenzoic acid with six different amino alcohols in the presence of
triphenylphosphine and N-bromosuccinimide. The derivatives were tested against
the Gram (+) bacteria Staphylococcus aureus and Bacillus cereus, Gram (-)
Pseudomonas aeruginosa and Escherichia coli, besides the yeast Candida albicans.
One of the compounds (7) was selectively active against C. albicans (91.3 +/-
0.49% inhibition) showing a great potential as a new drug lead, since it was more
active than the positive control, miconazole (88.7 +/- 2.41% inhibition).
Regarding bacterial inhibition, compounds demonstrated mild activity, but
inhibition of compounds 9, 10 and 13 towards E. coli is of interest since it is
difficult to find drugs selectively active against Gram (-) bacteria. Most of the
compounds were very active in the acetylcholinesterase inhibition assay. Compound
7 was again the most active (93.2 +/- 4.47%), being more potent than the control
galantamine (90.3 +/- 0.45%). The most active gallic acid derivatives, compounds
3, 7 and 8 have in common, besides gallic acid skeleton, a (CH2)2OH group, which
may be one of the structural requirements for AChE inhibition.
PMID- 29947669
TI - Decolorization of remazol brilliant blue R with laccase from Lentinus crinitus
grown in agro-industrial by-products.
AB - Lentinus crinitus is a white-rot fungus that produces laccase, an enzyme used for
dye decolorization. Enzyme production depends on cultivation conditions, mainly
agro-industrial by-products. We aimed to produce laccase from Lentinus crinitus
with agro-industrial by-products for dye decolorization. Culture medium had
coffee husk (CH) or citric pulp pellet (CP) and different nitrogen sources (urea,
yeast extract, ammonium sulfate and sodium nitrate) at concentrations of 0, 0.7,
1.4, 2.8, 5.6 and 11.2 g/L. Enzymatic extract was used in the decolorization of
remazol brilliant blue R. CH medium promoted greater laccase production than CP
in all evaluated conditions. Urea provided the greatest laccase production for CH
(37280 U/L) as well as for CP (34107 U/L). In CH medium, laccase activity was
suppressed when carbon-to-nitrogen ratio changed from 4.5 to 1.56, but the other
nitrogen concentrations did not affect laccase activity. For CP medium, reduction
in carbon-to-nitrogen ratio from 6 to 1.76 increased laccase activity in 17%. The
peak of laccase activity in CH medium occurred on the 11th day (41246 U/L) and in
CP medium on the 12th day (32660 U/L). The maximum decolorization within 24 h was
observed with CP enzymatic extract (74%) and with CH extract (76%).
PMID- 29947670
TI - Molecular characterization of Moenkhausia (Pisces: Characiformes) populations
with different lateral line developmental levels.
AB - The genera Hemigrammus and Moenkhausia have been traditionally diagnosed mainly
by the former having lateral line completely pored whereas the latter having a
lateral line with a few pored scales. Those features have been used to diagnose
species of both genera in the upper Parana River floodplain. Specimens with the
diagnostic features of Moenkhausia bonita, collected in the upper Parana River
floodplain, exhibited different developmental levels of the lateral line, making
it difficult to distinguish them from specimens of Hemigrammus sp. We analyzed
the gene encoding cytochrome C oxidase I (COI) and intron 1 of the nuclear gene
S7 to investigate the genetic similarities between the called Hemigrammus
marginatus and M. bonita and to confirm their identities. Molecular sequences of
other Moenkhausia species were analyzed for genus delimitation tests. The results
reveal genetic similarities of M. bonita specimens with different developmental
levels of the lateral line, and also distinguish between M. bonita and
Hemigrammus sp. Species delimitation tests revealed that specimens from the upper
Parana River floodplain were M. bonita and were distinct from other Moenkhausia
species. The developmental level of the lateral line is not a consistent
characteristic that distinguishes between Moenkhausia and Hemigrammus species.
PMID- 29947671
TI - Stratigraphic Relations of the Ipubi Formation: Siliciclastic-Evaporitic
Succession of the Araripe Basin.
AB - The Ipubi Formation represents the Aptian-Albian siliciclastic-evaporitic
succession of Araripe Basin, NE Brazil. This succession comprises siliciclastic
rocks (bituminous shales and claystones) and evaporites (gypsum and secondary
anhydrite) and represents part of the lacustrine-shallow marine post-rift phase
I. This study used sequence stratigraphy concepts to define the relations between
changes in the relative lake level and the formation of Ipubi deposits. Results
show that the organic-rich shales of the Ipubi Formation formed during a
transgressive pulse that covered large areas of the proximal domains. These
deposits overlie a regional unconformity that marks the end of the deposition of
the underlying Crato Formation. A High Stand stage that followed the
transgression influenced the formation of evaporitic deposits. Climate conditions
played a major role in influencing the triggering and stopping of evaporite
deposition. Thus, a new relative lake level fall event caused the exposure of the
Ipubi Formation deposits, and created another regional subaerial unconformity
accompanied by widespread karstification of evaporite beds. A posterior
transgression caused the deposition of siliciclastic rocks of the Romualdo
Formation over the Ipubi Formation strata, and also promoted a new event of
karstification of the Ipubi upper evaporite beds.
PMID- 29947673
TI - First record of the invasive tapeworm, Schyzocotyle acheilognathi
(Pseudophyllidea; Bothriocephalidae) in native freshwater fish, Brazil.
AB - Schyzocotyle acheilognathi is a tapeworm cestode commonly found in native
freshwater fishes from Asia. This cestode has low host specificity and for that
reason it has been registered parasitizing more than 200 cultured and wild fish
species, besides amphibians, reptiles and birds from different regions of the
world. With a high pathogenic potential, S. acheilognathi may cause mortalities
in highly infected fish. In South America, Schyzocotyle was reported in Cyprinus
carpio from a Brazilian fish farm at the municipality of Cornelio Procopio,
northern Parana State and from the natural environment in C. carpio from Neuquen
River, Patagonia, Argentina. So far, there has been no report of this parasite in
South American native fishes. Herein we report the first occurrence of the
invasive tapeworm S. acheilognathi in Rineloricaria pentamaculata (Siluriformes,
Loricariidae), a native armored freshwater catfish from southern Brazil.
PMID- 29947672
TI - Evaluation of an inexpensive needle test for the diagnosis of phosphorus
deficiency and management of phosphorus supplementation for cattle: A multiple
case study.
AB - The needle test (NT) is a point-of-care test developed in Brazil to evaluate the
Phosphorus (P) status in cattle. Based on bone resistance, the NT is a very
inexpensive method which allows the diagnosis of any degree of P deficiency in a
fast and simple way in vivo and directly on farm. The NT measures three levels of
resistance in the transverse process (TP) of the lumbar vertebrae: a) TP that are
impenetrable and result in warping of the needle (P healthy animals); b) TP
offering some resistance to the penetration (animals with subclinical P
deficiency); and c) TP which has minimal resistance to penetration (clinical P
deficiency). This manuscript presents results from a series of case studies to
evaluate the hypothesis that the NT could be used to assess P status in cattle
and assesses the usefulness of results to support decision making on mineral
supplementation strategies for grazing cattle. The NT was able to detect the
changes in the resistance patterns of the TP, as there was reduction or elevation
of P levels in the mineral mixtures. The NT was useful to assist in decision
making for adoption of mineral supplementation strategies better suited for each
farm, helping farmers to save money and avoid unnecessary waste of P.
PMID- 29947674
TI - Soil aggregation and carbon stabilization in burn and no-burn sugarcane
management systems.
AB - Retaining sugarcane straw over the soil after harvesting can improve soil
structure and increase soil carbon stabilization, mainly in macroaggregates. We
evaluated the carbon content in the aggregate classes in areas under burn and no
burn (adopted for five years) sugarcane management systems, focusing on the
superficial layer (0.00-0.20 m). The experiment was carried in an Oxisol and the
treatments consisted in burnt sugarcane, manual harvest; burnt sugarcane,
mechanized harvest; and no-burn, mechanized harvest. The retention of sugarcane
straw on the soil surface is justified by the increase in carbon content and
carbon stock in the surface layer (0.00-0.20 m) by restructuring of the soil,
even though it cannot match the structure of the soil under native forest. Our
results suggest that in no-burn management the carbon not occluded inside
aggregates was important to increase carbon stabilization in soil and that more
attention should be given to macroaggregates 2.00-8.00 mm present in this
management system, that showed higher carbon content and was responsible for
increase of the geometric and weight diameter, increasing the erosion resistance
in the long term in relation to burn systems.
PMID- 29947675
TI - Contulma vascaina sp. n. (Insecta: Trichoptera: Anomalopsychidae), a new species
from Rio de Janeiro state, southeastern Brazil.
AB - The caddisfly genus Contulma Flint, 1969, with 30 described species, is endemic
to the Neotropics. In addition to the five species currently recorded from
Brazil, a new species of Contulma is described and illustrated in this work.
Contulma vascaina sp. n. is similar to C. sana Jardim and Nessimian, 2011 in
prominent, slender and rod-like posterolateral lobe of segment IX, but the new
species has a shorter posterolateral lobe, with long, spine-like seta apically.
Contulma vascaina sp. n. can also be characterized by the presence of a large,
hood-like sclerotized plate on the endothecal phallic membrane. The female
genital structure is also described and illustrated.
PMID- 29947676
TI - Essential oils of green cumin and chamomile partially protect against acute
acetaminophen hepatotoxicity in rats.
AB - Essential oils of green cumin (Cuminum cyminum) and chamomile (Chamomilla
recutita) have antioxidant and anti-inflammatory effects. Acetaminophen, N-acetyl
p-amino-phenol, is an over-the-counter analgesic and antipyretic. Despite being
safe at therapeutic doses, acetaminophen overdose is a leading cause of acute
liver failure. This study aimed to compare the possible protective effects of
cumin and chamomile essential oils against acute acetaminophen hepatotoxicity in
male rats. Cumin oil (400 mg/kg) and chamomile oil (250 mg/kg) were orally
administered for 2 weeks prior to a single acetaminophen dose (1g/kg). Serum
liver function enzymes, oxidative stress markers in the liver and
histopathological features were evaluated. Acetaminophen caused marked damage to
hepatocytes evidenced by a significant rise in the levels of liver function
enzymes, including alanine aminotransferase and aspartate aminotransferase, and
disruption to the liver antioxidant protective system. Whereas the cumin oil
normalized acetaminophen-induced liver enzymes elevation, the chamomile oil
slightly attenuated the increase in alanine aminotransferase levels in
acetaminophen-intoxicated rats. The Chamomile oil moderately ameliorated
glutathione depletion and the decrease in superoxide dismutase activity in the
liver of acetaminophen-administered rats. The Cumin oil preserved the liver
structure to a greater extent than chamomile oil in acetaminophen-intoxicated
rats. Essential oils of cumin and chamomile partially counteracted acute
acetaminophen hepatotoxicity.
PMID- 29947677
TI - The identity of the mysterious "Azara's Parakeet" Sittace flaviventris Wagler,
1832.
AB - Sittace flaviventris Wagler, 1832 was the name given to Azara's No. 276 "Maracana
cabeza y encuentro roxos", but since then the identity of the species has
remained a mystery. Based on a tail-less domestic individual, it has most often
been attributed to an aberrant Aratinga parakeet, and is currently considered a
doubtful taxon. In this note the identity of "Azara's Parakeet" is confirmed as
Red-spectacled Amazon Amazona pretrei (Temminck, 1830), a species that still
occurs today in the region from where Azara described it. Sittace flaviventris is
thus a junior synonym of Amazona pretrei.
PMID- 29947678
TI - Nanoencapsulated Melaleuca alternifolia essential oil exerts anesthetic effects
in the brachyuran crab using Neohelice granulate.
AB - The aim of this study was to evaluate the efficacy and safety of several
anesthetics in the brachyuran crab Neohelice granulata, an emergent experimental
model. The essential oils (EOs) of Lippia alba, Aloysia tryphilla, and Melaleuca
alternifolia (tea tree oil; TTO), the isolated compounds eugenol, menthol,
terpinen-4-ol, and the nanoencapsulated form of TTO, were administered in one or
more of the following ways: added to the water (immersion), through an arthrodial
membrane (injected), or by oral gavage. Unexpectedly, most EOs did not produce an
anesthetic effect after immersion. Only TTO and eugenol induced anesthesia by
immersion, with very long induction and recovery times compared to anesthesia of
other crustaceans. However, a good anesthetic effect was observed with the
injection of terpinen-4-ol and nanoencapsulated TTO in N. granulata; both
demonstrated ideal induction and recovery times. These substances appear to be
promising anesthetic alternatives for crustaceans.
PMID- 29947679
TI - Accuracy of immunoglobulin M and immunoglobulin A of saliva in early diagnosis of
dengue: Systematic Review and Meta-analysis.
AB - The objective of the study was to conduct a systematic review to synthesize the
current evidence on the accuracy of IgM and IgA to early diagnosis the dengue
virus. The review protocol was registered at PROSPERO (CRD 42015024808). We
searched for studies in the following electronic database from 1990 to January
2018. The search identified 3507 studies. Five studies were included for
quantitative analysis. Three studies included evaluations of salivary IgM
provided a sensitivity of 86% and specificity of 93%. Two studies included
evaluating of IgA salivary showed a combined sensitivity of 69% and a combined
specificity of 98%. Despite the results found and the low methodological quality
of the studies included in the meta-analysis it is still soon to claim that IgA
is better than IgM to diagnosis Dengue.
PMID- 29947680
TI - Partum and postpartum characteristics on the postpartum rebreeding in beef
cattle.
AB - The objective was to evaluate the influence of calving and postpartum
characteristics, measured in different genetic predominance, on the postpartum
rebreeding. Were evaluated 437 partum from cows that received feeding management
consisting of a forage base of the native field and the mating season consisted
of 90 days. The measurements were used from the data base (age of cow, genetic
predominance, body weight, body condition score and date of calving) of the cows
in the partum and postpartum period. The variables were submitted to analysis of
multiple variances, multiple regression, correlation and cluster. Already the
groups formed by cluster analysis were submitted to analysis of variance and F
test and the means, compared by Student's t-test, alpha=0.05 probability. The
increase in the mean at 0.14 points in the body condition score at calving and
the occurrence of calving 9 days earlier at the calving season gives the
Charolais genetically predominant cows repeat calves. The Nellore genetic
predominance when they calved with similar body condition score (2.32 points) and
showed a negative body weight gain at weaning (-3.0 kg and -2.1 kg) showed
different behaviors, where they did not repeat the offspring, when they calved
and weaned with smaller body weight.
PMID- 29947681
TI - OUTCOME OF LAPAROSCOPIC CHOLECYSTECTOMY IN PATIENTS WITH GALLSTONE DISEASE AT A
SECONDARY LEVEL CARE HOSPITAL.
AB - BACKGROUND: Laparoscopic cholecystectomy is the most commonly performed operation
of the digestive tract. )It is considered as the gold standard treatment for
cholelithiasis. AIM: To evaluate the outcome of it regarding length of hospital
stay, complications, morbidity and mortality at a secondary hospital. METHODS:
Data of 492 patients who underwent laparoscopic cholecystectomy were
retrospectively reviewed. Patients' demographics, co-morbid diseases, previous
abdominal surgery, conversion to open cholecystectomy, operative time, intra and
postoperative complications, and hospital stay were collected and analyzed from
patients' files. RESULTS: Out of 492 patients, 386 (78.5%) were females and 106
(21.5%) males. The mean age of the patients was 49.35+/-8.68 years. Mean
operative time was 65.94+/-11.52 min. Twenty-four cases (4.9%) were converted to
open surgery, four due to obscure anatomy (0.8%), 11 due to difficult dissection
in Calot's triangle (2.2%) and nine by bleeding (1.8%). Twelve (2.4%) cases had
biliary leakage, seven (1.4%) due to partial tear in common bile duct, the other
five due to slipped cystic duct stables. Mean hospital stay was 2.6+/-1.5 days.
Twenty-one (4.3%) developed wound infection. Port site hernia was detected in
nine (1.8%) patients. There was no cases of bowel injury or spilled gallstones.
There was no mortality recorded in this series. CONCLUSIONS: Laparoscopic
cholecystectomy is a safe and effective line for management of gallstone disease
that can be performed with acceptable morbidity at a secondary hospital.
PMID- 29947682
TI - ERCP PERFORMANCE IN A TERTIARY BRAZILIAN CENTER: FOCUS ON NEW RISK FACTORS,
COMPLICATIONS AND QUALITY INDICATORS.
AB - BACKGROUND: ERCP can lead to complications, which can be prevented by the
recognition of risk factors. AIM: To identify these risk factors, with quality
evaluation. METHODS: Retrospective study in a Brazilian hospital in 194 patients,
excluding surgically altered anatomy. RESULTS: 211 ERCPs were performed: 97.6%
were therapeutic, 83.4% were started by trainees, with deep cannulation rate of
89.6%. Precut was needed in 16.6% of the ERCPs and classic sphincterotomy in
67.3%, with 75.4% of ductal clearance at single session and 8.0% of technical
failure. Inacessible papillas ocurred in 2.5% of cases. There were 2.5% of late
complications and 16% of early complications. Multivariate analysis identified
six predictors for early complications: fistulotomy precut (OR=3.4, p=0.010),
difficult cannulation (OR=21.5, p=0.002), attending's procedural time (OR=2.4,
p=0.020), choledocholithiasis (adjusted OR=1.8, p=0.015), cannulation time
(adjusted OR=3.2, p=0.018) and ERCP duration (adjusted OR=2.7, p=0.041).
CONCLUSION: Six risk factors for post-ERCP complications were identified. ERCP
duration and cannulation time are suggested as new potential quality indicators.
PMID- 29947683
TI - PHYSICAL ACTIVITY, QUALITY OF LIFE AND BODY IMAGE OF CANDIDATES TO BARIATRIC
SURGERY.
AB - BACKGROUND: Physical activity enhances quality of life and body image in obese.
Behavioural changes are useful tools to increase life conditions of this
population. AIM: To evaluate the physical activity level of candidates to
bariatric surgery and its relation with quality of life and body image, when
patients are encouraged weekly by personal trainers. ) Method: This is a
prospective, interventional and longitudinal study with quantitative analysis.
Patients were divided into two groups, control (n=28) and interventional (n= 10).
Both groups received physical activity and nutritional recommendations and
psychological support. Were used the SF36 and Body Shape questionnaires to assess
physical activity level and body image and pedometers to count weekly steps.
Patients were followed during 12 weeks. ) Results: Were found significant
difference in the domains physical activity (p=0.019), pain (p=0.0001) and health
general status (p=0.021). No significant difference in body weight (p=0.095) was
noted. CONCLUSION: When assisted by personal trainers, obese patients can change
behavior, increase health quality and physical activity levels and experience
less pain. Increase in physical activity, when well structured can benefit these
patients.
PMID- 29947684
TI - EUS-FNA WITH 19 OR 22 GAUGES NEEDLES FOR GASTRIC SUBEPITHELIAL LESIONS OF THE
MUSCLE LAYER.
AB - BACKGROUND: Tissue diagnosis is required for gastric subepithelial lesions for
differential diagnosis of GISTs. However, there has not been consensus about the
best needle for EUS-guided sampling of these lesions. AIM: To evaluate the
diagnostic yield of EUS-FNA for gastric subepithelial lesions of the proper
muscle layer with large-bore 19 gauge needles. METHODS: A prospectively
maintained database was retrospectively reviewed to identify consecutive patients
who underwent EUS-FNA with 19 and 22 gauge needles for gastric subepithelial
lesions of the fourth endosonographic layer in a tertiary care referral center.
EUS-FNA was performed by the same endosonographer, using the fanning technique,
without on-site cytopathologist. Specimens were analysed through cell blocks by
the same pathologist. Procedure results were categorized into diagnostic, defined
as enough material for histopathology and immunohistochemistry, or nondiagnostic.
RESULTS: Eighty-nine patients (mean age: 59 years, 77% women) underwent 92 EUS
FNA with 19 (75) or 22 (17) gauge needles. Mean lesion size was 22.6 mm. Overall
diagnostic yield was 88%. The diagnostic yield of 19 gauge was higher than that
of 22 gauge needle (92%x70.6%; p=0.0410), and similar for lesions >2 cm and <2 cm
(93.7%x90.7%; p=0.9563). The best performance for 19 gauge needles was obtained
performing <3 needle passes. Complication rate was 2.8%. CONCLUSIONS: Diagnostic
yield of EUS-FNA with 19 gauge needles is 92% for gastric subepithelial lesions
of the proper muscle layer. It is safe and highly valuable for differentiation
between GIST and leiomyoma, no matter the size of the lesion.
PMID- 29947685
TI - SALIVARY CORTISOL AND METABOLIC SYNDROME COMPONENT'S ASSOCIATION.
AB - BACKGROUND: Actually the lifestyle exposes the population to several risk factors
related to alimentary habits and less physical activity that contributes to
chronic diseases appearance worldwide. AIM: To analyze the association between
salivary cortisol and the components of metabolic syndrome. METHODS: This is a
cross-sectional study. As part of it, 28 individuals aged 30-59 years presenting
three or more of the following findings: CA: >=88 cm for women and >=102 cm for
men; SBP>130 mmHg and DBP>85 mmHg; GL>100 mg/dl; TG>150 mg/dl; HDL<40 mg/dl for
men and <50 mg/dl for women. Was performed analysis of salivary cortisol (by
radioimmunoassay) from 25 salivary samples collected throughout the day, for
evaluating changes in the circadian rhythm of this hormone (8AM, noon and 8PM).
RESULTS: 28 evaluated individuals had a mean age of 51.9+/-7.5 years, mostly
women (64.3%) and a mean of BMI 33.6+/-3.2 kg/m2. The cortisol level from the 8AM
averaged 18.7+/-4.8 ng/dlL. Individuals with FPG>110mg/dl, have significantly
lower average levels of cortisol than ones with FPG <110 (12.8+/-5,2 vs. 17.3+/
4.2). Significant correlations were HOMA vs. WC (r=0,465; p?0,005) and TG
(r=0,473; p?0,005), WC vs. FG (r=0,446; p?0,005) and BMI (r=0,730; p?0.0001); TG
vs. HDL (r=0,441 p?0,005) and FG (r=0,440; p?0,005). CONCLUSION: Morning salivary
cortisol in subjects with chronically elevated blood glucose can represent a
downregulation of the hypothalamic-pituitary adrenal axis. This is an important
finding not yet well investigated.
PMID- 29947686
TI - THE M-RNA, EXPRESSION OF SERCA2 AND NCX1 IN THE PROCESS OF PHARMACOLOGICAL CELL
PROTECTION IN EXPERIMENTAL ACUTE PANCREATITIS INDUCED BY TAUROCHOLATE.
AB - BACKGROUND: Intracellular calcium overload is known to be a precipitating factor
of pancreatic cell injury in acute pancreatitis (AP). Intracellular calcium
homeostasis depends of Plasmatic Membrane Calcium ATPase (PMCA), Sarcoplasmic
Endothelial Reticulum Calcium ATPase 2 (SERCA 2) and the Sodium Calcium Exchanger
(NCX1). The antioxidant melatonin (Mel) and Trisulfate Disaccharide (TD) that
accelerates NCX1 action could reduce the cell damage determined by the AP. AIM:
To evaluate m-RNA expressions of SERCA2 and NCX1 in acute pancreatitis induced by
sodium taurocholate in Wistar rats pre-treated with melatonin and/or TD. METHODS:
Wistar rats were divided in groups: 1) without AP; 2) AP without pre-treatment;
3) AP and Melatonin; 4) AP and TD; 5) AP and Melatonin associated to TD.
Pancreatic tissue samples were collected for detection of SERCA2 and NCX1 m-R NA
levels by polymerase chain reaction (PCR). RESULTS: Increased m-RNA expression of
SERCA2 in the melatonin treated group, without increase of m-RNA expression of
the NCX1. The TD did not affect levels of SERCA2 and NCX1 m-RNA expressions. The
combined melatonin and TD treatment reduced the m-RNA expression of SERCA2.
CONCLUSIONS: The effect of melatonin is restricted to increased m-RNA expression
of SERCA2. Although TD does not affect gene expression, its action in
accelerating calcium exchanger function can explain the slightest expression of
SERCA2 m-RNA when associated with Melatonin, perhaps by a joint action of drugs
with different and but possibly complementary mechanisms.
PMID- 29947687
TI - FUNCTIONALITY OF UPPER GASTROINTESTINAL CANCER PATIENTS WHICH HAVE UNDERTAKEN
SURGERY IN HOSPITAL PHASE.
AB - BACKGROUND: Cancer patients present various physiological, metabolic, social and
emotional changes as a consequence of the disease's own catabolism, and may be
potentiated in the gastrointestinal tract cancer by their interference with food
intake, digestion and absorption. AIM: o evaluate the functionality of upper
gastrointestinal cancer patients which have undertaken surgery and analyze the
factors associated with changes in strength and functionality during
hospitalization time. METHODS: Prospective analytical study in patients with
cancer of the upper gastrointestinal tract which have undertaken surgery. Was
evaluated the handgrip strength using a hand dynamometer and functionality
through the functional independence measure and Functional Status Scale for
Intensive Care Unit in the preoperative period, 2nd and 7th postoperative day.
RESULTS: Were included 12 patients, 75% men, and mean age was 58.17 years old.
The most prevalent tumor site was stomach (66.7%). There was a progressive
reduction from the pre-operative palmar grip strength to the 2nd and 7th
postoperative day, respectively. There was a decrease in functional performance
from the preoperative period to the 2nd and a gain from the 2nd to the 7th
postoperative day (p<0.001). CONCLUSION: An important reduction in the handgrip
strength and functionality was evidenced during the postoperative period in
relation to the basal value in the pre-operative period.
PMID- 29947688
TI - COMPARISON BETWEEN INCIDENCE OF INCISIONAL HERNIA IN LAPAROSCOPIC CHOLECYSTECTOMY
AND BY SINGLE PORT.
AB - BACKGROUND: Surgeries with single port access have been gaining ground among
surgeons who seek minimally invasive procedures. Although this technique uses
only one access, the incision is larger when compared to laparoscopic
cholecystectomy and this fact can lead to a higher incidence of incisional
hernias. AIM: To compare the incidence of incisional hernia after laparoscopic
cholecystectomy and by single port. METHODS: A total of 57 patients were randomly
divided into two groups and submitted to conventional laparoscopic
cholecystectomy (n=29) and laparoscopic cholecystectomy by single access (n=28).
The patients were followed up and reviewed in a 40.4 month follow-up for
identification of incisional hernias. RESULTS: Follow-up showed 21,4% of
incisional hernia in single port group and 3.57% in conventional technique.
CONCLUSIONS: There was a higher incidence of late incisional hernia in patients
submitted to single port access cholecystectomy compared to conventional
laparoscopic cholecystectomy.
PMID- 29947689
TI - LIVER RESECTION IN BRAZIL: A NATIONAL SURVEY.
AB - BACKGROUND: Liver surgery has developed significantly in the past decades. In
Brazil, the interest on it has grown significantly, but there is no study
regarding its clinical practice. Despite intrinsic limitations, surveys are well
suited to descriptive studies and allow understanding the current scenario. AIM:
To provide an overview on the current spread of liver surgery in Brazil, focusing
on groups' profile, operative techniques and availability of resources. METHOD:
From May to November 2016, was conducted a national survey about liver surgery
profile in Brazil composed by 28 questions concerning surgical team
characteristics, technical preferences, surgical volume, results and available
institutional resources. The survey was sent by e-mail to 84 liver surgery team
leaders from different centers including all regions of the country. RESULTS:
Forty-three study participants (51.2%), from all Brazilian regions, responded the
survey. Most centers have residency/fellowship programs (86%), perform and do
laparoscopic procedures (91%); however, laparoscopy is still responsible for a
little amount of surgeries (1-9% of laparoscopic procedures over all liver
resections in 39.5% of groups). Only seven centers (16.3%) perform more than 50
liver resections/year. Postoperative mortality rate is between 1-3% in 55% of the
centers. CONCLUSION: This is the first depiction of liver surgery in Brazil. It
showed a surgical practice aligned with worldwide excellence centers,
concentrated on hospitals dedicated to academic practice.
PMID- 29947690
TI - DEPRESSION, ANXIETY, AND BINGE EATING BEFORE AND AFTER BARIATRIC SURGERY:
PROBLEMS THAT REMAIN.
AB - BACKGROUND: As the number of surgeries increases and the elapsed time of the
realization increases as well, the postoperative evaluations would become
increasingly necessary. AIM: To assess the psychological profile before and after
surgery. METHODS: Were evaluated 281 patients from the public service of
bariatric surgery. In this study, 109 patients completed the evaluations before
surgery (T0) and up to 23 months after surgery (T1); 128 completed the
evaluations in T0 and between 24 months and 59 months after surgery (T2); and 44
completed the evaluations in T0 and 60 months after surgery (T3). A semi
structured interview, the Beck Depression Inventory (BDI), Beck Anxiety (BAI),
and the Binge Eating Scale (BES) were used. RESULTS: There was a higher
prevalence of female (83%), patients with less than 12 years of education (83%),
and patients who have a partner (64%). Analyzing all times of evaluation,
regarding anxiety, depression, and binge eating, there was a reduction in all
symptoms in T1, pointing to significant improvements in the first 23 months after
surgery. Already, in T2 and T3, there was an increase in all indicators of
anxiety, depression, and binge eating pointing to the transient impact of weight
loss or bariatric surgery on these symptoms. CONCLUSIONS: This study shows the
importance of the continuous psychological evaluation and needs for the
appropriate interventions for these patients who have undergone bariatric
surgery, even after weight loss.
PMID- 29947691
TI - PREVALENCE AND RISK FACTORS OF HYPERKALEMIA AFTER LIVER TRANSPLANTATION.
AB - BACKGROUND: There is a lack of data regarding hyperkalemia after liver
transplantation. AIM: To evaluate the prevalence of hyperkalemia after liver
transplantation and its associated factors. METHODS: This retrospective cohort
study evaluated 147 consecutive post-transplant patients who had at least one
year of outpatient medical follow up. The data collection included gender, age,
potassium values, urea, creatinine, sodium and medication use at 1, 6 and 12
months after. Hyperkalemia was defined as serum potassium concentrations higher
than 5.5 mEq/l. RESULTS: Hiperkalemia was observed in 18.4%, 17.0% and 6.1% of
patients 1, 6 and 12 months after tranplantation, respectively. Older age
(p=0.021), low creatinine clearance (p=0.007), increased urea (p=0.010) and
hypernatremia (p=0.014) were factors associated with hyperkalemia, as well as the
dose of prednisone at six months (p=0.014). CONCLUSION: Hyperkalemia was
prevalent in less than 20% of patients in the 1st month after liver
transplantation and decreased over time. Considering that hyperkalemia does not
affect all patients, attention should be paid to the routine potassium intake
recommendations, and treatment should be individualized.
PMID- 29947692
TI - PROGNOSTIC VALUE OF CARCINOEMBRYONIC ANTIGEN LEVELS IN TRANSOPERATIVE PERITONEAL
LAVAGE IN PATIENTS WITH GASTRIC CANCER.
AB - BACKGROUND: The carcinoembryonic antigen level in peritoneal lavage has been
showing to be a reliable prognostic factor in gastric cancer. AIM: To identify
any association between carcinoembryonic antigen level in peritoneal lavage, in
gastric cancer patients, with mortality, peritoneal recurrence, tumor relapse or
other prognostic factors. METHODS: In total, 30 patients (22 men, 8 women; median
age 66 years) with resectable gastric cancer (mainly stage III and IV) were
studied. Carcinoembryonic antigen level in peritoneal lavage was detected at
operation by immunocytochemical method and a level over 210 ng/g of protein was
considered as positive. RESULTS: There were detected 10 positive cases (33.3%) of
plCEA levels. These levels were associated with mortality, RR: 2.1 (p=0.018);
peritoneal recurrence, OR: 9.0 (p=0.015); and relapse or gastric cancer
progression, OR: 27.0 (p=0.001). CONCLUSION: Increased levels of plCEA fairly
predicts mortality, peritoneal recurrence tumor relapse or cancer progression.
PMID- 29947693
TI - EARLY ORAL FEEDING POST-UPPER GASTROINTESTINAL TRACT RESECTION AND PRIMARY
ANASTOMOSIS IN ONCOLOGY.
AB - BACKGROUND: The practice of starving patients in the immediate period after upper
gastrointestinal surgery is widespread. Early oral intake has been shown to be
feasible and may result in faster recovery and decrease length of hospital. AIM:
To evaluate the feasibility and safety of oral nutrition on postoperative early
feeding after upper gastrointestinal surgeries. METHODS: Observational cohort
design study with convenience retrospective data in both genders, over 18 years,
undergoing to total gastrectomy and/or elective esophagectomy. They have received
oral or enteral nutrition in less than 48 h after surgery, and among those who
started with enteral nutrition, the oral feeding up to seven days. RESULTS: The
study was performed in 161 patients, 24 (14.9%) submitted to esophagectomy, 132
(82%) to total gastrectomy and five (3.1%) to esophagogastrectomy. Was observed
good dietary acceptance and low percentage (29%) of gastrointestinal
intolerances, more pronounced among those with enteral diet. Most of the patients
did not present postoperative complications, 11 (6.8%) were reopened, five (3.1%)
had fistulas, three (1.9%) wound dehiscence, three (1.9%) fistula more wound
dehiscence and six (3.7%) other non-infectious complications. CONCLUSION: Early
oral diet is safe and viable for patients undergoing upper gastrointestinal
surgery.
PMID- 29947694
TI - HIGHER VALUES IN LIVER ELASTOGRAPHY AND MELD SCORE ARE MORTALITY PREDICTORS ON
LIVER TRANSPLANT WAITING LIST.
AB - BACKGROUND: Liver elastography have been reported in hepatocellular carcinoma
(HCC) with higher values; however, it is unclear to identify morbimortality risk
on liver transplantation waiting list. AIM: To assess liver stiffness, ultrasound
and clinical findings in cirrhotic patients with and without HCC on screening for
liver transplant and compare the morbimortality risk with elastography and MELD
score. METHOD: Patients with cirrhosis and HCC on screening for liver transplant
were enrolled with clinical, radiological and laboratory assessments, and
transient elastography. RESULTS: 103 patients were included (without HCC n=58
(66%); HCC n=45 (44%). The mean MELD score was 14.7+/-6.4, the portal
hypertension present on 83.9% and the mean transient elastography value was
32.73+/-22.5 kPa. The median acoustic radiation force impulse value of liver
parenchyma was 1.98 (0.65-3.2) m/s and 2.16 (0.59-2.8) m/s in HCC group. The HCC
group was significantly associated with HCV infection (OR 26.84; p<0.0001),
higher levels of serum alpha-fetoprotein (OR 5.51; p=0.015), clinical portal
hypertension (OR 0.25; p=0.032) and similar MELD score (p=0.693). The area under
the receiver operating characteristics (AUROC) showed sensitivity and specificity
for serum alpha-fetoprotein (cutoff 9.1 ng/ml), transient elastography value
(cutoff value 9 kPa), and acoustic radiation force impulse value (cutoff value
2.56 m/s) of 50% and 86%, 92% and 17% and 21% and 92%, respectively. The survival
group had a mean transient elastography value of 31.65+/-22.2 kPa vs. 50.87+/
20.9 kPa (p=0.098) and higher MELD scores (p=0.035). CONCLUSION: Elastography,
ultrasound and clinical findings are important non-invasive tools for cirrhosis
and HCC on screening for liver transplant. Higher values in liver elastography
and MELD scores predict mortality.
PMID- 29947695
TI - NON-INVASIVE PREVENTIVE VENTILATION WITH TWO PRESSURE LEVELS IN THE POSTOPERATIVE
PERIOD OF ROUX-EN-Y GASTRIC BYPASS: RANDOMIZED TRIAL.
AB - BACKGROUND: Obesity is characterized by excessive accumulation of body fat, which
causes damage to the health of individuals, such as breathing difficulties. AIM:
To verify the results of non-invasive ventilation as a preventive strategy on the
decline of respiratory function and postoperative complications in patients
undergoing Roux-en-Y gastric bypass. METHODS: This is a randomized trial,
according to CONSORT standards, with obese adults aged 18-40 years. Randomized
control group (n=25) only received guidelines regarding posture, early ambulation
and cough stimuli, and in the NIV group (n=25), in addition to the aforementioned
group, non-invasive ventilation was performed with two pressure levels, once day
for 60 min, from the 1st to the 3rd postoperative day (POD). Both groups were
evaluated in the preoperative period and in the 1st and 3rd POD for respiratory
function, which were: slow vital capacity (VC), inspiratory capacity (IC), minute
volume (MV), tidal volume maximal inspiratory muscle strength (Pimax) and peak
expiratory flow (PEF). The length of hospital stay and the episodes of
postoperative complications were recorded. RESULTS: Of the 50 patients the
majority were young adults with degrees of obesity between III and IV. In the
intergroup analysis, there was an improvement in the CVL and MV only in the 1st
POD in the NIV group, CI in the three moments evaluated in the NIV group and the
PFE in the 1st and 3rd PDO also in this group. The most frequent complications
were pneumonia, followed by operative wound infection and atelectasis. There was
a significant difference between groups, showing a higher occurrence in pneumonia
and atelectasis in the control group. The days of hospitalization and intensive
care unit were similar. CONCLUSION: It was observed a faster recovery until the
3rd POD in the IC and PEF variables in the NIV group; in addition, there were
fewer complications in this group.
PMID- 29947696
TI - TRUNK BODY MASS INDEX: A NEW REFERENCE FOR THE ASSESSMENT OF BODY MASS
DISTRIBUTION.
AB - BACKGROUND: Body mass index (BMI) has some limitations for nutritional diagnosis
since it does not represent an accurate measure of body fat and it is unable to
identify predominant fat distribution. AIM: To develop a BMI based on the ratio
of trunk mass and height. METHODS: Fifty-seven patients in preoperative
evaluation to bariatric surgery were evaluated. The preoperative anthropometric
evaluation assessed weight, height and BMI. The body composition was evaluated by
bioimpedance, obtaining the trunk fat free mass and fat mass, and trunk height.
Trunk BMI (tBMI) was calculated by the sum of the measurements of the trunk fat
free mass (tFFM) and trunk fat mass (tFM) in kg, divided by the trunk height
squared (m2)). The calculation of the trunk fat BMI (tfBMI) was calculated by
tFM, in kg, divided by the trunk height squared (m2)). For the correction and
adjustment of the tBMI and tfBMI, it was calculated the relation between trunk
extension and height, multiplying by the obtained indexes. RESULTS: The mean data
was: weight 125.3+/-19.5 kg, height 1.63+/-0.1 m, BMI was 47+/-5 kg/m2) and trunk
height was 0.52+/-0,1 m, tFFM was 29.05+/-4,8 kg, tFM was 27.2+/-3.7 kg, trunk
mass index was 66.6+/-10.3 kg/m2, and trunk fat was 32.3+/-5.8 kg/m2. In 93% of
the patients there was an increase in obesity class using the tBMI. In patients
with grade III obesity the tBMI reclassified to super obesity in 72% of patients
and to super-super obesity in 24% of the patients. CONCLUSION: The trunk BMI is
simple and allows a new reference for the evaluation of the body mass
distribution, and therefore a new reclassification of the obesity class,
evidencing the severity of obesity in a more objectively way.
PMID- 29947697
TI - Coarse particles and hospital admissions due to respiratory diseases in children.
An ecological time series study.
AB - BACKGROUND: Exposure to particulate matter (PM) is associated with
hospitalizations due to respiratory diseases among children. DESIGN AND SETTING:
An ecological time series study was carried out to identify the role of coarse
fractions of particulate matter (PM10-2.5) in hospitalizations among children up
to 10 years of age, in Piracicaba (SP) in the year 2015. METHODS: A generalized
additive model of Poisson regression was used to estimate the risk of
hospitalization due to acute laryngitis and tracheitis, pneumonia, bronchitis,
bronchiolitis and asthma. Lags of 0 to 7 days were considered, and the model was
adjusted for the temperature and relative humidity of the air and controlled for
short and long-term exposure. Proportional attributable ratios, population
attributable fractions and hospital costs were calculated with increasing
concentrations of these pollutants. RESULTS: 638 hospitalizations were evaluated
during this period, with a mean of 1.75 cases per day (standard deviation, SD =
1.86). The daily averages were 22.45 ug/m3 (SD = 13.25) for the coarse fraction
(PM10-2.5) and 13.32 ug/m3 (SD = 6.38) for the fine fraction. Significant risks
of PM10-2.5 exposure were only observed at lag 0, with relative risk (RR) =
1.012, and at lag 6, with RR = 1.011. An increase of 5 ug/m3 in the coarse
fraction concentration implied an increase in the relative risk of
hospitalizations of up to 4.8%, with an excess of 72 hospitalizations and excess
expenditure of US$ 17,000 per year. CONCLUSIONS: This study showed the impact of
coarse-fraction exposure on hospital admissions among children due to respiratory
diseases.
PMID- 29947698
TI - Social, behavioral and biological correlates of cardiorespiratory fitness
according to sex, nutritional status and maturity status among adolescents. A
cross-sectional study.
AB - BACKGROUND: Our aim was to analyze multilevel correlates of cardiorespiratory
fitness (CRF) according to sex, nutritional status and maturity status among
adolescents. DESIGN AND SETTING: Cross-sectional study conducted in public
schools. METHODS: This was a cross-sectional study on 1,209 adolescents aged
between 10 and 17 years. CRF was estimated from the 20-meter shuttle run test.
Anthropometric data on body mass index and waist circumference were obtained.
Somatic maturation was assessed from the peak height velocity. Questionnaires
were used to evaluate socioeconomic variables (family income, parents' education
level and number of siblings) and behavioral variables (physical activity, screen
time and alcohol and tobacco consumption) among the parents and adolescents.
RESULTS: Boys, adolescents with normal weight and on-time maturers presented
greater CRF (P < 0.05). Concerning socioeconomic correlates, girls (tobacco
smoking, alcohol consumption, physical activity and screen time), adolescents
with normal weight (alcohol consumption, physical activity and screen time), and
on-time maturers (alcohol consumption, physical activity during childhood and
habitual physical activity) demonstrated higher numbers of behavioral correlates
with CRF. Normal-weight adolescents presented a higher number of biological
correlates (chronological age, age at peak height velocity and waist
circumference). CONCLUSIONS: Different correlates were observed according to sex,
nutritional status and somatic maturation status. However, habitual physical
activity, waist circumference and chronological age seemed to be the strongest
factors associated with cardiorespiratory fitness among adolescents.
PMID- 29947700
TI - Assessment of chronic wounds in adults: an integrative review.
AB - OBJECTIVE: To identify the main aspects that should be assessed in adults with
chronic wounds. METHOD: This was an integrative review of the scientific
literature published between 2010 and early 2015 in the PubMed and Web of Science
databases. RESULTS: Few studies exclusively address wound assessment. However,
the review found many aspects to consider when assessing individuals with ulcers,
grouped as follows: factors that significantly affect healing or the development
of new wounds (age, nutritional status, functional capacity, or comorbidities),
pyschosocial factors, and wound characteristics (location, size, depth, type of
tissue, time of evolution). CONCLUSION: The literature search did not result in
any one aspect that must be considered when assessing chronic wounds, but a
complex interaction of factors that include both physiological and social and
psychological elements. Professionals should be aware of this multifactorial
approach to achieve early detection of the development and evolution of ulcers
and to intervene accordingly.
PMID- 29947701
TI - Giving Voice to Caregivers: a game for family caregivers of dependent
individuals.
AB - OBJECTIVE: To construct and assess a board game created to promote the effective
transition of family members into caregivers of dependent individuals. METHOD:
This was a qualitative exploratory and descriptive case study conducted with
family caregivers of dependent individuals. RESULTS: The study resulted in the
conceptualization, construction, and assessment of the board game. The game
proved to be an important family evaluation tool, enabling open communication and
interventions in family dynamics. CONCLUSION: The results showed that the game
can help build new family narratives, providing an opportunity for open
communication, expression of problems and sharing, representing an important
family evaluation and intervention strategy.
PMID- 29947699
TI - What do Cochrane systematic reviews say about new practices on integrative
medicine?
AB - BACKGROUND: This study identified and summarized all Cochrane systematic reviews
(SRs) on the effects of ten integrative practices that were recently added to the
Brazilian public healthcare system (SUS). DESIGN AND SETTING: Review of
systematic reviews, conducted in the Discipline of Evidence-Based Medicine,
Escola Paulista de Medicina (EPM), Universidade Federal de Sao Paulo (Unifesp).
METHODS: Review of Cochrane SRs on the following interventions were identified,
summarized and critically assessed: apitherapy, aromatherapy, bioenergetics,
family constellation, flower therapy, chromotherapy, geotherapy, hypnotherapy,
hand imposition or ozone therapy. RESULTS: We included a total of 16 SRs: 4 on
apitherapy, 4 on aromatherapy, 6 on hypnotherapy and 2 on ozone therapy. No
Cochrane SR was found regarding bioenergetics, family constellation,
chromotherapy, clay therapy, flower therapy or hand imposition. The only high
quality evidence was in relation to the potential benefit of apitherapy,
specifically regarding some benefits from honey dressings for partial healing of
burn wounds, for reduction of coughing among children with acute coughs and for
preventing allergic reactions to insect stings. CONCLUSION: Except for some
specific uses of apitherapy (honey for burn wounds and for acute coughs and bee
venom for allergic reactions to insect stings), the use of ten integrative
practices that have recently been incorporated into SUS does not seem to be
supported by evidence from Cochrane SRs.
PMID- 29947702
TI - The nursing team's performance towards the sexuality of institutionalized elderly
women.
AB - OBJECTIVE: Analyzing how the nursing team performs in facing the sexuality in the
daily lives of institutionalized elderly women. METHOD: A qualitative and
descriptive study carried out in a Nursing Home in the southern region of Brazil.
Data were collected from April to July 2016 through a semi-structured interview
and submitted to the French Discourse Analysis of Michel Pecheux. The study
complied with the norms of the Brazilian legislation for research on human
beings. RESULTS: Eighteen (18) nursing professionals participated in the study.
Ideological and imaginary formations permeated the subjects' discourse, evoking
the understanding of sexuality, its institutional conformation and the
performance demanded under manifestations of this sexuality. Thus, considering
the professionals' performance, it became possible to identify difficulties such
as embarrassment, discomfort or prevalence of personal beliefs and strategies.
These strategies have diversified ranging from the use of humor to direct
repressive actions. CONCLUSION: Understanding the dynamics of professionals'
performance towards sexuality allows us to glimpse the need for comprehensiveness
in care related to social, ideological and imaginary formations which demand an
imperative strengthening of academic and professional training.
PMID- 29947703
TI - Proposal of nursing diagnoses, outcomes and interventions for postoperative
patients of orthognathic surgery.
AB - OBJECTIVE: To propose nursing diagnoses, outcomes and interventions for patients
in the postoperative period of orthognathic surgery. METHOD: Secondary analysis
of an information bank of a focal group with five patients submitted to
orthognathic surgery. The classifications of the North American Nursing Diagnosis
Association International, Nursing Outcomes Classification and Nursing
Interventions Classification were used for elaborating nursing diagnoses,
outcomes and interventions. Nursing diagnoses were identified based on the
transcription of the focus group and the expected outcomes and interventions were
proposed. In the second stage, the material was submitted to an analysis by
judges for validating the previous stage. RESULTS: After careful analysis of the
retrieved information, nine nursing diagnoses that relate to both the
difficulties already installed and to potential patient difficulties were
identified. After this phase, the expected outcomes for nursing care and the
appropriate interventions for the postoperative period at home were identified.
CONCLUSION: Given the short hospital stay and the long postoperative period, the
established actions have a strong educational focus.
PMID- 29947704
TI - Be Sweet to Babies: evaluation of an instructional video on neonatal pain
management by nurses.
AB - OBJECTIVE: To describe the profile of nurses who work in hospital units that care
for newborns; to verify nurses' prior knowledge on breastfeeding, skin-to-skin
care and sweet tasting solutions for neonatal procedural pain relief; and to
evaluate nurses' perceptions on the feasibility, acceptability and usefulness of
the Portuguese version of the "Be Sweet to Babies" video. METHOD: A cross
sectional study conducted in four units of a university affiliated hospital in
Sao Paulo. Forty-five (45) nurses who answered the questionnaire and watched the
video were included. Thirty-eight (38) nurses subsequently evaluated the video.
Descriptive statistics were used to analyze the variables, in addition to content
analysis of the open question. RESULTS: Forty-five (45) nurses participated in
the study; 97.4% were aware of the analgesic strategies, and after watching the
video nurses reported that they intend to use or encourage the use of these
strategies during painful procedures. All participants would recommend the video
to other professionals, and considered the resource as useful, easy to understand
and easy to apply in real situations. CONCLUSION: Nurses are aware of the
analgesic strategies and they considered the video as a feasible, acceptable and
useful tool for knowledge translation to health care providers, which can also
favor parental involvement in their children's pain management.
PMID- 29947705
TI - The scenario of scientific publication on palliative care in oncology over the
last 5 years: a scoping review.
AB - OBJECTIVE: To identify the profile of studies published on palliative care in
oncology and to analyze their levels of evidence. METHOD: A scoping review.
Inclusion criteria published in the last 5 years, in English, Portuguese or
Spanish. Exclusion criteria incomplete articles, paid for, or those without
results. RESULTS: The search resulted in 42,650 publications, where 341 remained
after four selection steps. The largest number of publications was in 2015, with
32.55% of the total; 83% were classified as Recommendation Grade B, and 52% with
Level of Evidence 2B. Uniprofessional production was more frequent with 67.74% of
the publications; physicians were the authors in 93.26%, and nurses in 25.22% of
the total articles. CONCLUSION: There are several articles on the subject,
however they have low scientific evidence. Most of the production is
uniprofessional, and nurses are the main authors of multiprofessional
publications. A brief overview of the scientific publication on palliative care
in oncology was performed, from which we can recommend integration among
professionals for producing multiprofessional studies with better quality of
scientific evidence to direct and improve healthcare.
PMID- 29947706
TI - Actions for health advocacy and user empowerment by nurses of the Family Health
Strategy.
AB - OBJECTIVE: To understand the actions for health advocacy and user empowerment
developed by nurses of the Family Health Strategy in Brazil. METHOD: A
qualitative study carried out with nurses working in the Family Health Strategy
in a city in the South of Brazil. Participants were selected by non
probabilistic, snowball sampling. Data was collected from a semi-structured
interview guide, recorded, transcribed and analyzed through discursive textual
analysis. RESULTS: Fifteen (15) nurses participated in the study. Three
categories emerged: user participation; health environments; health advocacy
actions related to the multiprofessional team. CONCLUSION: The closer
relationship that the Family Health Strategy enables between the
multiprofessional team, users and the community promotes health advocacy
practices, while user empowerment favors autonomy in health care, encouraging a
healthier life and enabling them to intervene in the health decisions of the
local community.
PMID- 29947707
TI - Nursing Diagnoses of incarcerated mothers.
AB - OBJECTIVE: To identify the Nursing Diagnoses of incarcerated nursing mothers by
the NANDA-I Taxonomy II. METHOD: Descriptive/exploratory study developed in the
Women's Penal Colony, Recife, PE. RESULTS: The sample consisted of 18 women who
were breastfeeding during the study period. A total of 17 diagnoses were listed,
whose accuracy was classified as moderate and high by the Nursing Diagnoses
Accuracy Scale (EADE, version 2). Five of these diagnoses were selected for
discussion, regarding frequency, magnitude, and impact on the health and well
being of nursing mothers participating in the study. CONCLUSION: The Nursing
Diagnoses identified in this study are not exclusive to nursing mothers who are
incarcerated. Some factors relevant to the prison environment may aggravate their
problems, which reveal situations of health vulnerability and rights violation.
These situations require changes that may respond to the health needs of this
target population.
PMID- 29947708
TI - Evaluation of the self-eye examination method for health promotion.
AB - OBJECTIVE: To evaluate the self-eye examination practice as a tool to promote the
ocular self-evaluation. METHOD: Quasi-experimental study developed in a
university of Piaui with sample of 324 students between January and May 2014. A
team of thirteen researchers made observations during the self-examination
followed by an ocular screening. RESULTS: There was no agreement on the
hypothesis of defense that the ocular exam could help to observe the eyes health,
p-value>0.3. However, the exam was considered as easy to accomplish (99.7%) and
that not only the physician can perform the eye exam (99.4%). The awareness about
eye care is identified as the main purpose of this booklet (97.6%), (chi2=
186.01; p=0.001). The results highlight the booklet can be used in the teaching
process of self-eye examination (84.6%). Although the defense that its fulfilment
can replace the consultation with the ophthalmologist (23.8%%) cannot be accepted
(chi2= 46.34), the self-exam must be done routinely (82.4%). CONCLUSION: The
results prove that the learning through virtual booklet is possible and supports
self-care with the eyes by performing the self-exam.
PMID- 29947709
TI - Adherence of mental therapy for mental disorder patients to drug health treatmen.
AB - OBJECTIVE: To assess the adherence of mental disorder patients to drug therapy
for mental health treatment and the association between demographic,
socioeconomic, clinical and pharmacotherapeutic variables to treatment adherence.
METHOD: A cross-sectional study conducted with mental disorder patients in two
Psychosocial Care Centers in Curitiba/Parana in 2014. Data from structured
interviews and medical records were submitted to descriptive and bivariate
analysis. RESULTS: 300 patients with mental disorders participated in the study.
51% of participants adhered to the drug therapy, the highest adherence was among
males with no family history of mental disorder, diagnosed with schizophrenia,
with disease duration of less than 1 year, who did not forget to take the
medicine not even once in the previous month and who relied on family
participation. Adherence was lower among the interviewees with individual income
lower than one minimum wage, perception of regular and poor health, diagnosis of
depression associated with another disorder, treatment time in the service over 2
years and with a history of attempted suicide. CONCLUSION: Low adherence to the
drug therapy was observed. The variables associated with adherence were gender,
individual income, family history of mental disorder, perception about their
health, diagnosis of mental disorder, duration of illness and treatment, suicide
attempt, failing to take the medication at least once in the previous month and
family participation.
PMID- 29947710
TI - Predictors of death in an Intensive Care Unit: contribution to the palliative
approach.
AB - OBJECTIVE: To identify predictors of death in the Intensive Care Unit and relate
eligible patients to preferential palliative care. METHOD: A prospective cohort
study that evaluated patients hospitalized for more than 24 hours, subdivided
into G1 (patients who died) and G2 (patients who were discharged from hospital).
For identifying the predictors for death outcome, the intensivist physician was
asked the "surprise question" and clinical-demographic data were collected from
the patients. Data were analyzed by descriptive/inferential statistics (p<0.05
significance). RESULTS: 170 patients were evaluated. The negative response to the
"surprise question" was related to death outcome. A greater possibility of death
(p<0.05) was observed among older and more frail patients with less
functionality, chronic cardiac and/or renal insufficiencies or acute non
traumatic neurological insult, with multiorgan failure for more than 5 days, and
hospitalized for longer. CONCLUSION: Predictors of death were related to a
subjective evaluation by the physician, the clinical condition of the patient,
underlying diseases, the severity of the acute disease and the evolution of the
critical illness. It is suggested that patients with two or more predictive
criteria receive preferential palliative care.
PMID- 29947711
TI - Validation and reliability of the rapid diagnostic test 'SD Bioeasy Dengue Duo'
for dengue diagnosis in Brazil: a phase III study.
AB - BACKGROUND: The diagnosis of dengue is complex. Until recently, only specialised
laboratories were able to confirm dengue infection. However, this has changed
with the newly available immunochromatographic rapid tests. Early diagnosis is of
great interest, and point-of-care rapid tests have been increasingly used in
Brazil. Most of those tests have not undergone validation in the Brazilian
population. In this context, we decided to evaluate a rapid test introduced in
the Federal District (FD). OBJECTIVES: To estimate the accuracy and reliability
of the SD Bioeasy Dengue Duo rapid test and its components to detect dengue
infections in a consecutive sample of symptomatic residents in the FD, Brazil.
METHODS: In total, 1353 venous blood samples were collected between 2013 and
2014. Two hundred and six positive samples (cases) and 246 negative samples (non
cases) were required for sensitivity and specificity estimation, respectively;
for agreement evaluation, we used 401 samples. The reference standard used was a
composite of MAC-ELISA, virus isolation and real-time polymerase chain reaction
(RT-qPCR). The evaluation was conducted prospectively under field conditions in
the public health units of the FD. FINDINGS: The results for the overall accuracy
of the rapid test (NS1/IgM combined) showed 76% sensitivity and 98% specificity.
The sensitivity for the NS1 component (67%) was better than that for the IgM
component (35%). The positive likelihood ratio was 46, and the negative
likelihood ratio was 0.24. The reliability of the test (NS1/IgM combined)
demonstrated crude agreement of 98% (Kappa index 0.94). MAIN CONCLUSIONS: The
present phase III, large-scale validation study demonstrates that the rapid test
SD Bioeasy Dengue Duo has moderate sensitivity (NS1/IgM combined) and high
specificity. Therefore, the test is useful in confirming the diagnosis of dengue,
but not enough to rule out the diagnosis. Our results also suggest that Dengue
virus (DENV) viral load estimated through the RT-qPCR and antibody level measured
through the MAC-ELISA could have had a direct influence on the accuracy of the
rapid test.
PMID- 29947712
TI - Imported case of Dengue virus 3 genotype I in Rio de Janeiro state, Brazil.
AB - The dengue virus (DENV), of the genus Flavivirus (Flaviviridae), has four
antigenically distinct serotypes, of which DENV-3 is classified into five
genotypes. Here, we describe the detection of DENV-3 genotype I in sera of a
Brazilian patient travelling from Singapore to Rio de Janeiro, Brazil, by using
multiplex real-time RT-PCR, DNA sequencing of the whole envelope protein gene,
and phylogenetic analysis. The virus shares ancestry with those identified in
Bali, Indonesia, in 2015. It is possible that arboviruses such as Chikungunya
ECSA genotype, DENV-4 genotype I, and Zika were introduced in Brazil from other
continents during the multiple international events hosted by the country over
the last four years, including World Youth Day, the Soccer World Cup, and the
Summer Olympics.
PMID- 29947713
TI - Melanin particles isolated from the fungus Fonsecaea pedrosoi activates the human
complement system.
AB - BACKGROUND: Melanin production has been associated with virulence in various
pathogenic fungi, including Fonsecaea pedrosoi, the major etiological agent for
chromoblastomycosis, a subcutaneous fungal disease that occurs in South America.
OBJECTIVE: The aim of this study was to evaluate the effects of acid-basic
extracted F. pedrosoi melanin particles and fungal cell ghosts obtained by
Novozym 234 treatment on their ability to activate the human complement system.
METHODS: The ability of melanin particles and fungal cell ghosts to activate the
human complement system was evaluated by complement consumption,
immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). FINDINGS:
Unsensitised melanin particles and melanin ghosts presented complement
consumption of 82.67 +/- 2.08% and 96.04 +/- 1.13%, respectively.
Immunofluorescence assays revealed intense deposition of the C3 and C4 fragments
on the surface of melanin particles and ghosts extracted from F. pedrosoi.
Deposition of the C3, C4, and C5 fragments onto melanin samples and zymosan was
confirmed by ELISA. Deposition of small amounts of C1q and C9 onto melanin
samples and zymosan was detected by ELISA. CONCLUSION: Fonsecaea pedrosoi melanin
particles and fungal cell ghosts activated the complement system mainly through
an alternative pathway.
PMID- 29947714
TI - Correlation of lung function and respiratory muscle strength with functional
exercise capacity in obese individuals with obstructive sleep apnea syndrome.
AB - OBJECTIVE: To evaluate lung function and inspiratory muscle strength, correlating
them with exercise tolerance, in obese individuals with obstructive sleep apnea
syndrome (OSAS). METHODS: The sample comprised 31 adult subjects with moderate-to
severe OSAS diagnosed by polysomnography. We used spirometry to measure FVC,
FEV1, and FVC/FEV1 ratio, using pressure manometry to measure MIP and MEP. The
incremental shuttle walk test (ISWT) and the six-minute walk test (6MWT) were
used in order to determine functional exercise capacity. RESULTS: In this sample,
the mean values for FVC (% of predicted), FEV1 (% of predicted): MIP, and MEP
were 76.4 +/- 12.3%, 80.1 +/- 6.3%, 60.0 +/- 21.9 cmH2O, and 81.3 +/- 22.2 cmH2O,
respectively. The mean distances covered on the ISWT and 6MWT were 221 +/- 97 m
and 480.8 +/- 67.3 m, respectively. The ISWT distance showed moderate positive
correlations with FVC (r = 0.658; p = 0.001) and FEV1 (r = 0.522; p = 0.003).
CONCLUSIONS: In this sample of obese subjects with untreated OSAS, lung function,
inspiratory muscle strength, and exercise tolerance were all below normal. In
addition, we found that a decline in lung function, but not in respiratory muscle
strength, was associated with exercise tolerance in these patients.
PMID- 29947715
TI - Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from
inpatients at a tertiary care hospital.
AB - OBJECTIVE: To evaluate Streptococcus pneumoniae serotypes isolated from an
inpatient population at a tertiary care hospital, in order to determine the
theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and
the 23-valent pneumococcal polysaccharide vaccine (PPV23). METHODS: This was a
cross-sectional study involving 118 inpatients at the Hospital Sao Lucas, in the
city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or
other sterile body fluid specimens, collected between January 2005 and December
2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied
in relation to the serotypes identified in the sample and their relationship with
those contained in the pneumococcal vaccines available in Brazil. RESULTS: The
majority of the population was male (n = 66; 55.9%), with a median age of 57
years (interquartile range: 33-72 years). The most common manifestation was
pneumonia, and the pneumococcus was most commonly isolated from blood cultures.
More than one fourth of the study population had some degree of immunosuppression
(n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no
significant associations between mortality and comorbidity type, ICU admission,
or need for mechanical ventilation. The theoretical vaccine coverage of PPV23
alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. CONCLUSIONS: If the
patients in this sample had been previously vaccinated with PCV13 plus PPV23,
theoretically, 50.8% of the cases of invasive pneumococcal disease that required
hospital admission could potentially have been prevented. Invasive pneumococcal
disease should be prevented by vaccination not only of children and the elderly
but also of adults in their economically productive years, so as to reduce the
socioeconomic costs, morbidity, and mortality still associated with the disease,
especially in underdeveloped countries.
PMID- 29947716
TI - Mini-thoracostomy with vacuum-assisted closure: a minimally invasive alternative
to open-window thoracostomy.
AB - Thoracostomy is a common treatment option for patients with stage III pleural
empyema who do not tolerate pulmonary decortication. However, thoracostomy is
considered mutilating because it involves a thoracic stoma, the closure of which
can take years or require further surgery. A new, minimally invasive technique
that uses the vacuum-assisted closure has been proposed as an alternative to
thoracostomy. This study aims to analyze the safety and effectiveness of mini
thoracostomy with vacuum-assisted closure in an initial sample of patients.
PMID- 29947717
TI - Asthma control, lung function, nutritional status, and health-related quality of
life: differences between adult males and females with asthma.
AB - OBJECTIVE: To evaluate health-related quality of life in asthma patients treated
at a referral center in southern Brazil, identifying differences between male and
female patients, as well as to evaluate differences between the males and females
in terms of asthma control, lung function, and nutritional status. METHODS: This
was a cross-sectional study involving patients >= 18 years of age treated at an
asthma outpatient clinic. We evaluated clinical parameters, lung function,
nutritional status, and quality of life. RESULTS: A total of 198 patients
completed the study. The mean age was 56.2 +/- 14.8 years, and 81.8% were female.
The proportion of patients with uncontrolled asthma was higher among females than
among males (63.0% vs. 44.4%; p = 0.041). The body mass index (BMI) and
percentage of body fat were higher in females than in males (30.2 +/- 5.8 kg/m2
vs. 26.9 +/- 4.5 kg/m2 and 37.4 +/- 6.4% vs. 26.5 +/- 7.4%; p = 0.002 and p <
0.001, respectively). Quality of life was lower in females than in males in the
following domains: symptoms (3.8 +/- 1.5 vs. 4.6 +/- 1.7; p = 0.006); activity
limitation (3.6 +/- 1.3 vs. 4.4 +/- 1.5; p = 0.001); emotional function (3.6 +/-
1.9 vs. 4.5 +/- 1.7; p = 0.014); and environmental stimuli (3.2 +/- 1.6 vs. 4.3
+/- 1.9; p = 0.001). CONCLUSIONS: Male asthma patients appear to fare better than
do female asthma patients in terms of health-related quality of life, asthma
control, BMI, percentage of body fat, and comorbidities.
PMID- 29947718
TI - Use of adductor pollicis muscle thickness in hospitalized or ambulatory patients:
a systematic review.
AB - OBJECTIVE: to analyze the use of the Adductor Pollicis Muscle Thickness (APMT) as
an anthropometric parameter and prognostic indicator in hospitalized or
ambulatory patients. METHOD: systematic review carried out the Web of Science,
SCOPUS and Lilacs databases. RESULTS: Twenty-three studies were performed on
critical, surgical, oncological, nephropathic and hepatopathic patients,
collecting data on bibliographic reference, study site, objectives, number of
patients, age group, methodology, main results and conclusion. APMT proved to be
a good anthropometric parameter for evaluation of nutritional status in critical
patients without edema, and surgical, oncological and nephropathic patients, but
presented poor performance for diagnosis of malnutrition in hepatopathic
patients. It was a good prognostic indicator for mortality in critical,
nephropathic and oncological patients, and also a good predictor of
hospitalization in nephropathic patients. There was an association with
neurological complications in Hepatic Encephalopathy (HE) in the case of
hepatophatic patients, but it was not a predictor of postoperative complications
in surgical patients. CONCLUSION: APTM was considered a good anthropometric
parameter in most clinical conditions, except in patients with liver disease and
a good prognostic indicator for mortality in critical, oncological and
nephropathic patients, and a predictor of neurological complications in HE.
Further prognostic investigation, standardization of cutoff points and evaluation
of sensitivity and specificity are required.
PMID- 29947719
TI - Catheter-directed thrombolysis for patients with acute lower extremity deep vein
thrombosis: a meta-analysis.
AB - OBJECTIVES: To evaluate case series studies that quantitatively assess the
effects of catheter-directed thrombolysis (CDT) and compare the efficacy of CDT
and anticoagulation in patients with acute lower extremity deep vein thrombosis
(DVT). METHODS: Relevant databases, including PubMed, Embase, Cochrane, Ovid
MEDLINE and Scopus, were searched through January 2017. The inclusion criteria
were applied to select patients with acute lower extremity DVT treated with CDT
or with anticoagulation. In the case series studies, the pooled estimates of
efficacy outcomes for patency rate, complete lysis, rethrombosis and post
thrombotic syndrome (PTS) were calculated across the studies. In studies
comparing CDT with anticoagulation, summary odds ratios (ORs) were calculated.
RESULTS: Twenty-five articles (six comparing CDT with anticoagulation and 19 case
series) including 2254 patients met the eligibility criteria. In the case series
studies, the pooled results were a patency rate of 0.87 (95% CI: 0.85-0.89),
complete lysis 0.58 (95% CI: 0.40-0.75), rethrombosis 0.11 (95% CI: 0.06-0.17)
and PTS 0.10 (95% CI: 0.08-0.12). Six studies comparing the efficacy outcomes of
CDT and anticoagulation showed that CDT was associated with a reduction of PTS
(OR 0.38, 95%CI 0.26-0.55, p<0.0001) and a higher patency rate (OR 4.76, 95%CI
2.14-10.56, p<0.0001). CONCLUSION: Acute lower extremity DVT patients receiving
CDT were found to have a lower incidence of PTS and a higher incidence of patency
rate. In our meta-analysis, CDT is shown to be an effective treatment for acute
lower extremity DVT patients.
PMID- 29947720
TI - Support actions undertaken for the woman by companions in public maternity
hospitals.
AB - OBJECTIVE: to identify the support actions undertaken for the woman during labor,
birth, cesarean section and the postpartum period. METHOD: a transversal study,
undertaken in three public maternity hospitals, with a sample of 1,147
companions. The data were collected through interviews and were analyzed using
descriptive statistics. The support actions were classified in four dimensions:
emotional, physical, informational and relating to intermediation. RESULTS: the
majority of interviewees were the partner/father of the baby (76.7%). In labor,
birth and the postpartum period, the actions of emotional support - such as
calming, encouraging and praising, were performed by more than 80.0% of the
companions; informational support, by approximately 70.0%; and intermediation by
fewer than 65.0% of them. In childbirth, the emphasis on physical support was
observed in assisting with walking (84.4%), and in changing position (90.4%).
CONCLUSION: the companions participate actively in the birth process, performing
actions of support in the four dimensions. Emotional support is the most
frequent, followed by physical and informational support, mainly during labor and
birth. The results contribute to valuing the companion from the woman's social
network in the birth scenario and to the recognition of his/her role as a
provider of support.
PMID- 29947721
TI - Erratum.
AB - [This corrects the article doi: 10.1590/s1984-29612017080].
PMID- 29947723
TI - EPIDEMIOLOGICAL INVISIBILITY CHARACTERIZES BRAZILIAN NATIVE INDIANS' HEALTH.
PMID- 29947722
TI - Whole genome sequence of Mycobacterium kansasii isolates of the genotype 1 from
Brazilian patients with pulmonary disease demonstrates considerable
heterogeneity.
AB - Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly
encountered species in individuals with lung disease. We here report the complete
genome sequence of 12 clinical isolates of M. kansasii from patients with
pulmonary disease in Brazil.
PMID- 29947724
TI - INFANT FEEDING IN THE FIRST TWO YEARS OF LIFE.
AB - OBJECTIVE: To analyze the prevalence of breastfeeding and the introduction of
complementary food for zero to 24-month-old infants. METHODS: This is a
population-based cross-sectional study of children aged less than 24 months in
Montes Claros, Minas Gerais, Brazil. Data were collected in 2015, by interviews
with people in charge of infant care in the house. The questionnaire administered
assessed the sociodemographic status of the family, maternal and infant
characteristics and food consumption habits. Survival analysis was used to
calculate median prevalence and duration of breastfeeding and the introduction of
complementary feeding. RESULTS: With 180 days of life, 4.0% of the children were
exclusively breastfed, 22.4% were mostly breastfed and 43.4% were fed breast milk
as complementary food. In the third month of life, children were consuming water
(56.8%), fruit juice or formula (15.5%) and cow's milk (10.6%). At the age of 12
months, 31.1% were consuming artificial juice and 50.0% were eating candies.
Before the age of 1 year, 25.0% of them had already eaten instant noodles.
CONCLUSIONS: The introduction of drinks, honey, sugar and candies as
complementary food was found to be premature; and solid and semi-solid foods were
almost appropriate. The habits described can directly affect the success of
breastfeeding. Given that the inadequate eating practices identified can
compromise the infant's health, actions that promote breastfeeding and provide
guidance on the introduction of complementary foods are important.
PMID- 29947725
TI - ERRATUM.
AB - [This corrects the article doi: 10.1590/1984-0462/;2018;36;2;00015].
PMID- 29947726
TI - Extension of Disease Risk Score-Based Confounding Adjustments for Multiple
Outcomes of Interest: An Empirical Evaluation.
AB - Use of disease risk score (DRS)-based confounding adjustment when estimating
treatment effects on multiple outcomes is not well studied. We designed an
empirical cohort study to compare dabigatran initiators and warfarin initiators
with respect to risks of ischemic stroke and major bleeding in 12 sequential
monitoring periods (90 days each), using data from the Truven Marketscan database
(Truven Health Analytics, Ann Arbor, Michigan). We implemented 2 approaches to
combine DRS for multiple outcomes: 1) 1:1 matching on prognostic propensity
scores (PPS), created using DRS for bleeding and stroke as independent variables
in a propensity score (PS) model; and 2) simultaneous 1:1 matching on DRS for
bleeding and stroke using Mahalanobis distance (M-distance), and compared their
performance with that of traditional PS matching. M-distance matching appeared to
produce more stable results in the early marketing period than both PPS and
traditional PS matching; hazard ratios from unadjusted analysis, traditional PS
matching, PPS matching, and M-distance matching after 4 periods were 0.72 (95%
confidence interval (CI): 0.51, 1.03), 0.61 (95% CI: 0.31, 1.09), 0.55 (95% CI:
0.33, 0.91), and 0.78 (95% CI: 0.45, 1.34), respectively, for stroke and 0.65
(95% CI: 0.53, 0.80), 0.78 (95% CI: 0.60, 1.01), 0.75 (95% CI: 0.59, 0.96), and
0.78 (95% CI: 0.64, 0.95), respectively, for bleeding. In later periods,
estimates were similar for traditional PS matching and M-distance matching but
suggested potential residual confounding with PPS matching. These results suggest
that M-distance matching may be a valid approach for extension of DRS-based
confounding adjustments for multiple outcomes of interest.
PMID- 29947727
TI - The double burden of malnutrition among adolescents: analysis of data from the
Global School-Based Student Health and Health Behavior in School-Aged Children
surveys in 57 low- and middle-income countries.
AB - Background: Adults and young children in countries experiencing the nutrition
transition are known to be affected simultaneously by undernutrition and
overnutrition. Adolescence is a critical period for growth and development. Yet,
it is unknown to what extent this double burden of malnutrition affects
adolescents in low- and middle-income countries (LMICs) and the macrolevel
contextual factors associated with the double burden of malnutrition. Objective:
The aim was to quantify the magnitude of the double burden of malnutrition among
adolescents and to examine the potential sources of heterogeneity in prevalence
estimates across LMICs. Design: We used individual-participant data from the
Global School-Based Student Health and Health Behavior in School-Aged Children
surveys conducted in 57 LMICs between 2003 and 2013, comprising 129,276
adolescents aged 12-15 y. Pooled estimates of stunting, thinness, or both;
overweight or obesity; and concurrent stunting and overweight or obesity were
calculated overall, by regions, and stratified by sex, with random-effects meta
analysis. Guided by UNICEF's conceptual framework for child malnutrition, we used
ecological linear regression models to examine the association between macrolevel
contextual factors (internal conflict, lack of democracy, gross domestic product,
food insecurity, urbanization, and survey year) and stunting, thinness, and
overweight and obesity prevalence, respectively. Results: The prevalence of
stunting was 10.2% (95% CI: 8.3%, 12.2%) and of thinness was 5.5% (95% CI: 4.3%,
6.9%). The prevalence of overweight or obesity was 21.4% (95% CI: 18.6%, 24.2%).
Between 38.4% and 58.7% of the variance in adolescent malnutrition was explained
by macrolevel contextual factors. The prevalence of concurrent stunting and
overweight or obesity was 2.0% (95% CI: 1.7%, 2.5%). Conclusions: The double
burden of malnutrition among adolescents in LMICs is common. Context-sensitive
implementation and scale-up of interventions and policies for the double burden
of malnutrition are needed to achieve the Sustainable Development Goal to end
malnutrition in all of its forms by 2030. This trial was registered at
clinicaltrials.gov as NCT03346473.
PMID- 29947728
TI - Time Perspective and All-Cause Mortality: Evidence From the English Longitudinal
Study of Ageing.
AB - Background: Long-term future thinking has been associated with a range of
favorable health behaviors. However, it is currently unclear whether this
translates into an effect on morbidity and mortality. Purpose: The goal of this
study was to study the relationship between time perspective and all-cause
mortality and to examine the role of health behavior in explaining this
association. Methods: Participants (N = 9,949) aged 50 and over from the English
Longitudinal Study of Ageing, a representative cohort of older English adults,
estimated the length of their personal time horizon for financial planning (time
perspective). Two thousand ninety-two deaths were recorded over a 9-year follow
up period (2002/2003-2012). Smoking, physical activity, and alcohol consumption
were examined as factors that may underlie the time perspective-mortality link.
Results: Our prospective survival analyses showed that those who tend to plan for
longer periods experienced a significantly reduced risk of all-cause mortality
(HR = 0.83; 95% confidence interval [CI]: [0.80, 0.87], p < .001 per 1 SD
increase in future time perspective). This association remained after adjusting
for baseline socioeconomic status and health (HR = 0.92; 95% CI: [0.88, 0.97], p
< .001). The link between time perspective and mortality was observed across the
gradient of financial circumstances and did not appear to be due to reverse
causality. Healthy behavior among the more future orientated explained 34% of the
link between time perspective and mortality. Conclusions: Using a simply
administered indicator of time perspective, this study suggests that a future
orientated time perspective may be an important predictor of reduced risk of
death.
PMID- 29947729
TI - Pictorial Warning Labels and Memory for Cigarette Health-risk Information Over
Time.
AB - Background: Pictorial cigarette warning labels are thought to increase risk
knowledge, but experimental research has not examined longer-term effects on
memory for health risks named in text. Purpose: To investigate memory
consolidation predictions that high- versus low-emotion warnings would support
better long-term memory for named cigarette health risks and to test a
mediational model of warning-label effects through memory on risk perceptions and
quit intentions. Methods: A combined sample of U.S.-representative adult smokers,
U.S.-representative teen smokers/vulnerable smokers, and Appalachian
representative adult smokers were randomly assigned to a warning-label condition
(High-emotion pictorial, Low-emotion pictorial, Text-only) in which they were
exposed four times to nine warning labels and reported emotional reactions and
elaboration. Memory of warning-label risk information, smoking risk perceptions,
and quit intentions were assessed immediately after exposures or 6 weeks later.
Results: Recall of warning-label text was low across the samples and supported
memory-consolidation predictions. Specifically, immediate recall was highest for
Low-emotion warnings that elicited the least emotion, but recall also declined
the most over time in this condition, leaving its 6-week recall lowest; 6-week
recall was similar for High-emotion and Text-only warnings. Greater recall was
associated with higher risk perceptions and greater quit intentions and mediated
part of warning-label effects on these important smoking outcomes. High-emotion
warnings had additional non-memory-related effects on risk perceptions and quit
intentions that were superior to text-only warnings. Conclusions: High- but not
Low-emotion pictorial warning labels may support the Food and Drug
Administration's primary goal to "effectively convey the negative health
consequences of smoking." ClinicalTrials.gov Identifier: NCT03375840.
PMID- 29947730
TI - Sex Differences in the Association between Heavy Drinking and Behavioral Distress
Tolerance and Emotional Reactivity Among Non-Depressed College Students.
AB - Background: Heavy episodic drinking (HED) is a common behavior among college
students that is associated with severe negative consequences. Negative
reinforcement processes have been applied to elucidate mechanisms underlying
relationships between consumption of alcohol and the desire to alleviate negative
feelings. Distress tolerance (DT) and emotional reactivity are two mechanisms
that are consistent with the self-medication model that may contribute to HED.
The current study investigated relationships between DT, emotional reactivity,
defined as frustration reactivity and irritability reactivity, and HED in a non
depressed college population. Given differential patterns of consumption and
motivation for drinking between males and females, sex differences were also
examined. Short Summary: The study examined two constructs consistent with
negative reinforcement processes, behavioral distress tolerance (DT) and
emotional reactivity (frustration reactivity and irritability reactivity), to
explain heavy episodic drinking (HED) among non-depressed college students.
Behavioral DT and frustration reactivity independently predicted HED. Higher HED
was associated with higher frustration reactivity and lower behavioral DT in
women, but nor in men. Methods: One-hundred-ten college students without
depressive symptoms completed alcohol use measures and the Paced Auditory Serial
Attention Task (PASAT-C) to assess behavioral DT and emotional reactivity.
Results: DT and frustration reactivity independently predicted HED. The
association between DT and HED was moderated by sex such that higher levels of DT
predicted higher HED among females, but not among males. Higher frustration
reactivity scores were associated with a greater number of HED. Conclusions:
Results provide supporting evidence that DT and emotional reactivity are distinct
factors, and that they predict HED independently. Results underscore the
importance of examining sex differences when evaluating the association between
HED and negative reinforcement processes in this population.
PMID- 29947732
TI - Longitudinal Associations Between Provision of Autonomy Support and Well-Being in
Spouses of Individuals With Chronic Pain.
AB - Background: Caregiving spouses of individuals with chronic pain often experience
poor well-being. Purpose: The current study aimed to examine the association
between chronic pain-related provision of autonomy support and well-being in
support providers (spouses) of individuals with chronic pain. Methods: Spouses of
individuals with a diagnosed musculoskeletal chronic pain condition (N = 172)
were recruited for a five-time point longitudinal study. Participants completed
the questionnaires once every 6 months across 2 years. In a follow-up diary
study, participants (N = 41) completed daily records of provision of autonomy
support and well-being. Results: Multilevel analyses showed that provision of
autonomy support was associated with greater well-being in support providers at
both within-person and between-person levels. Longitudinal cross-lagged analyses
also provided some evidence that it is provision of autonomy support that
predicts well-being, and not the opposite. These effects held true in the follow
up diary study; however, some findings also suggested that the short-term
associations between provision of autonomy support and well-being could be
reciprocal. Conclusions: Current findings extend the existing literature by
suggesting provision of autonomy support as a beneficial type of support for the
provider within the chronic pain context and lay the groundwork for caregiver
focused interventions.
PMID- 29947731
TI - Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a
multicenter retrospective follow-up study from the Cutaneous Lymphoma
International Consortium.
PMID- 29947733
TI - Are Spouses' Sleep Problems a Mechanism Through Which Health is Compromised?
Evidence Regarding Insomnia and Heart Disease.
AB - Background: Symptoms of insomnia have been widely identified as risk factors for
health, including heart disease. Despite the expansive and growing literature on
health concordance among coupled individuals, few studies have examined insomnia
as a shared risk factor for heart disease among middle-aged and older couples.
Purpose: This study examined the association between insomnia and incident heart
disease among couples. A dyadic modeling approach was employed to investigate the
relationships between one's own insomnia and partners' insomnia for the risk of
incident heart disease for each partner. Methods: Data from the 2010, 2012, and
2014 Health and Retirement Study were utilized in a prospective research design
(N = 3,221 couples). Actor-partner interdependence models were employed to
estimate actor and partner effects of insomnia symptoms for incident heart
disease over the 4 year observation period. Results: Insomnia symptoms measured
at baseline were related to an increased risk for heart disease for husbands,
whereas for wives the association was attenuated after other health measures were
controlled. Wives' insomnia was related to an increased risk of incident heart
disease for husbands but husbands' insomnia was not related to wives' risk of
heart disease. Conclusions: This study showed how subjective insomnia symptoms
among middle-aged and older adults in intimate partnerships are associated with
their heart disease risk. Further research is needed to verify the results with
objective measures of sleep problems and heart disease.
PMID- 29947734
TI - A Sensitive Assay for Proteases in Bioaerosol Samples: Characterization and
Quantification of Airborne Proteases in Salmon Industry Work Environments.
AB - Proteases are probably underestimated exposure agents in bioaerosols. Their roles
as barrier disrupters in allergic sensitization and activators of innate
inflammation call for more attention in exposure-response studies. The main
objectives of this study was (i) to establish a suitable method for detection of
small quantities of proteases in filtered air samples and (ii) to utilize the
method to characterize exposure to proteases in a salmon industry work
environment. Analysis of proteases in filtered air samples was based on
zymography, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis with
0.1% gelatin as substrate added in the polyacrylamide gel. Gelatinase activity
was evident as cleared (unstained) regions. The area of these regions was
quantified using image analysis (UVP Vision Works(r)). Standard curves with known
amounts of active porcine trypsin were added to each gel. Validation of 11 non
linear standard curves showed R2 (range) = 0.8989-0.9882, limit of detection =
0.056 nM, lower limit of quantification = 0.161 nM, and coefficients of
variations (range) = 20-28%. Sampling of bioaerosols in salmon industry was
performed using polytetrafluoretylene filters with an airflow of 3 l min-1. All
samples contained visible bands close to the size of porcine trypsin (23.3 kDa).
The bands did not disappear in the presence of EDTA but abolished by Pefabloc,
demonstrating that the enzyme is a serine protease, most likely salmon trypsin.
Airborne levels of active protease were below the statistical detection limit in
the filleting department but quantifiable in extract samples from the slaughter
department. Three filtered air samples from the slaughter department showed air
concentrations of 6.2, 16.5, and 27.0 ng m-3 air. We conclude that zymography is
a sensitive and reliable method for exposure assessment of active proteases in
indoor environmental samples. We recommend this assay for use in occupational
studies to characterize and quantify exposure to active proteases in bioaerosols.
PMID- 29947735
TI - Effects of spatial patterning of co-flowering plant species on pollination
quantity and purity.
AB - Background and Aims: If two plant species share pollinators, it has been proposed
that the interaction between them may range from competitive to facilitative,
depending on the way in which they intermingle. In particular, the presence of a
rewarding plant species may increase the rate of pollinator visitation to a less
rewarding species in its vicinity, but the beneficial increase in visitation may
be counteracted by a detrimental increase in heterospecific pollen transfer. We
assessed this trade-off using bumble-bees foraging over a gradual spatial
transition between two plant species in an indoor cage experiment. Methods: We
used two 'species' of artificial flowers - one more rewarding than the other - in
arrays that varied in the degree of species intermingling. The flowers dispensed
and received powdered food dyes serving as pollen analogues. Captive bumble-bees
visited to collect sucrose solution. We quantified dye delivery to the adhesive
tape 'stigmas' in flowers by spectrophotometry. Key Results: Across the spatial
transition between species, the less attractive species received more dye (more
bee visits) when in proximity to the more attractive species than it did when
alone, but the larger dye loads were less pure (more heterospecific pollen
transfer). The decline in purity cancelled out the gain in acquisition, so
conspecific pollen receipt by the less attractive species was neutrally affected.
The more attractive species received fewer visits when surrounded by the less
attractive species, so the interaction between the two species was amensalism
when considering conspecific pollen reception. Conclusions: Pollinator-mediated
interactions between plant species depend on pollination quantity and purity,
both of which can depend on spatial intermingling.
PMID- 29947736
TI - Prolonged Leisure Time Spent Sitting in Relation to Cause-Specific Mortality in a
Large US Cohort.
AB - The majority of leisure time is spent in sedentary behaviors such as television
viewing. Studies have documented that prolonged leisure-time sitting is
associated with higher risk of mortality-total, cardiovascular disease, cancer,
and "all other causes"-but few have examined the "other" causes of death in
detail. To examine associations of leisure-time sitting with risk of specific
causes of death, we analyzed data from the Cancer Prevention Study II (CPS-II)
Nutrition Cohort, a prospective US cohort including 127,554 men and women who
were free of major chronic disease at study entry, and among whom 48,784 died
during 21 years of follow-up (1993-2014; median follow-up, 20.3 years,
interquartile range, 4.6 years). After multivariable adjustment, prolonged
leisure-time sitting (>=6 vs. <3 hours per day) was associated with higher risk
of mortality from all causes, cardiovascular disease (including coronary heart
disease and stroke-specific mortality), cancer, diabetes, kidney disease,
suicide, chronic obstructive pulmonary disease, pneumonitis due to solids and
liquids, liver, peptic ulcer and other digestive disease, Parkinson disease,
Alzheimer disease, nervous disorders, and musculoskeletal disorders. These
findings provide additional evidence for associations between a broad range of
mortality outcomes and prolonged sitting time. Given the pervasive nature of
sitting in the contemporary lifestyle, this study further supports the
recommendation that encouraging individuals to reduce sedentary time may provide
health benefits.
PMID- 29947737
TI - GeneCT: a generalizable cancerous status and tissue origin classifier for pan
cancer biopsies.
AB - Motivation: Tissue biopsy is commonly used in cancer diagnosis and molecular
studies. However, advanced skills are required for determining cancerous status
of biopsies and tissue origin of tumor for cancerous ones. Correct classification
is essential for downstream experiment design and result interpretation,
especially in molecular cancer studies. Methods for accurate classification of
cancerous status and tissue origin for pan-cancer biopsies are thus urgently
needed. Results: We developed a deep learning-based classifier, named GeneCT, for
predicting cancerous status and tissue origin of pan-cancer biopsies. GeneCT
showed high performance on pan-cancer datasets from various sources and
outperformed existing tools. We believe that GeneCT can potentially facilitate
cancer diagnosis, tumor origin determination and molecular cancer studies.
Availability and implementation: GeneCT is implemented in Perl/R and supported on
GNU/Linux platforms. Source code, testing data and webserver are freely available
at http://sunlab.cpy.cuhk.edu.hk/GeneCT/. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29947738
TI - Optimizing Patient Outcomes and Safety With Liposuction.
AB - Since its advent in the early 1980s, liposuction has made tremendous
advancements, making it the most popular aesthetic surgery performed today. The
goal of this Continuing Medical Education (CME) article is provide a foundation
of knowledge of the relevant anatomy, preoperative evaluation, intraoperative
technique, and postoperative management for surgeons performing liposuction.
Finally, the prevention and management of potential complications, will be
reviewed along with measures to optimize patient safety and outcomes.
PMID- 29947739
TI - The choice of sequence homologs included in multiple sequence alignments has a
dramatic impact on evolutionary conservation analysis.
AB - Motivation: The analysis of sequence conservation patterns has been widely
utilized to identify functionally important (catalytic and ligand-binding)
protein residues for over a half-century. Despite decades of development, on
average state-of-the-art non-template-based functional residue prediction methods
must predict ~25% of a protein's total residues to correctly identify half of the
protein's functional site residues. The overwhelming proportion of false
positives results in reported "F-Scores" of ~0.3. We investigated the limits of
current approaches, focusing on the so-far neglected impact of the specific
choice of homologs included in multiple sequence alignments (MSAs). Results: The
limits of conservation-based functional residue prediction were explored by
surveying the binding sites of 1,023 proteins. A straightforward conservation
analysis of MSAs composed of randomly selected homologs sampled from a PSI-BLAST
search achieves average F-Scores of ~0.3, a performance matching that reported by
state-of-the-art methods, which often consider additional features for the
prediction in a machine learning setting. Interestingly, we found that a simple
combinatorial MSA sampling algorithm will in almost every case produce an MSA
with an optimal set of homologs whose conservation analysis reaches average F
Scores of ~0.6, doubling state-of-the-art performance. We also show that this is
nearly at the theoretical limit of possible performance given the agreement
between different binding site definitions. Additionally, we showcase the
progress in this direction made by Selection of Alignment by Maximal Mutual
Information (SAMMI), an information-theory-based approach to identifying
biologically informative MSAs. This work highlights the importance and the unused
potential of optimally composed MSAs for conservation analysis. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29947741
TI - Will FTLD-tau work for all when FTDP-17 retires?
PMID- 29947742
TI - Meta-Analysis of the Association Between Anti-Tumour Necrosis Factor Use and
Lymphoma Risk in Patients With Inflammatory Bowel Disease: Methodological
Considerations.
PMID- 29947743
TI - Function determinants of TET proteins: the arrangements of sequence motifs with
specific codes.
AB - The ten-eleven translocation (TET) proteins play a crucial role in promoting
locus-specific reversal of DNA methylation, a type of chromatin modification.
Considerable evidences have demonstrated that the sequence motifs with specific
codes are important to determine the functions of domains and active sites. Here,
we surveyed major studies and reviews regarding the multiple functions of the TET
proteins and established the patterns of the motif arrangements that determine
the functions of TET proteins. First, we summarized the functional sequence basis
of TET proteins and identified the new functional motifs based on the
phylogenetic relationship. Next, we described the sequence characteristics of the
functional motifs in detail and provided an overview of the relationship between
the sequence motifs and the functions of TET proteins, including known functions
and potential functions. Finally, we highlighted that sequence motifs with
diverse post-translational modifications perform unique functions, and different
selection pressures lead to different arrangements of sequence motifs, resulting
in different paralogs and isoforms.
PMID- 29947744
TI - Reply: Will FTLD-tau work for all when FTDP-17 retires?
PMID- 29947745
TI - Maltreatment during childhood: a risk factor for the development of
endometriosis?
AB - STUDY QUESTION: Is maltreatment during childhood (MC), e.g. sexual abuse,
physical abuse, emotional abuse and neglect, associated with diagnosis of
endometriosis? SUMMARY ANSWER: Childhood sexual abuse, emotional abuse/neglect
and inconsistency experiences were associated with the diagnosis of endometriosis
while no such association was found for physical abuse/neglect and other forms of
maltreatment. WHAT IS KNOWN ALREADY: Symptoms of endometriosis such as chronic
pelvic pain, fatigue and depression, are correlated with MC, as are immune
reactions linked to endometriosis. These factors support a case for a potential
role of MC in the development of endometriosis. STUDY DESIGN, SIZE, DURATION: The
study was designed as a multicentre retrospective case-control study. Women with
a diagnosis of endometriosis were matched to control women from the same
clinic/doctor's office with regard to age (+/-3 years) and ethnic background. A
total of 421 matched pairs were included in the study. PARTICIPANTS/MATERIALS,
SETTING, METHODS: Women with endometriosis and control women were recruited in
university hospitals, district hospitals, and doctors' offices in Germany,
Switzerland and Austria. A German-language version of the Childhood Trauma
Questionnaire (CTQ) was used to evaluate MC. Diagnosis of endometriosis was
confirmed histologically and classified according to ASRM criteria. MAIN RESULTS
AND THE ROLE OF CHANCE: Women with endometriosis reported significantly more
often than control women a history of sexual abuse (20%/14%, P = 0.0197),
emotional abuse (44%/28%, P < 0.0001), emotional neglect (50%/42%, P = 0.0123)
and inconsistency experiences (53%/41%, P = 0.0007). No statistically significant
differences could be demonstrated for physical abuse/neglect (31%/26%, P =
0.1738). Combinations of different abuse/neglect experiences were described
significantly more often in women with endometriosis. Frequencies of other MC,
i.e. violence against the mother (8%/7%, P = 0.8222), drug abuse in the family
(5%/3%, P = 0.0943), mentally handicapped family members (1%/1%, P = 0.7271),
suicidal intentions in the family (6%/4%, P = 0.2879) and family members in
prison (1%/1%, P = 0.1597) were not statistically different in women with
endometriosis and control women. LIMITATIONS, REASONS FOR CAUTION: Some control
women might present asymptomatic endometriosis, which would lead to
underestimation of our findings. The exclusion of pregnant women may have biased
the results. Statistical power for sub-analyses of physical abuse/neglect and
sexual abuse was limited. WIDER IMPLICATIONS OF THE FINDINGS: A link to MC needs
to be considered in women with endometriosis. As there are effective strategies
to avoid long-term consequences of MC, healthcare professionals should inquire
about such experiences in order to be able to provide treatment for the
consequences as early as possible. STUDY FUNDING/COMPETING INTEREST(S): None.
TRIAL REGISTRATION NUMBER: Endo_QoL NCT 02511626.
PMID- 29947747
TI - Erratum.
PMID- 29947748
TI - Cardiac resynchronization therapy in heart failure: is the defibrillator needed?
PMID- 29947746
TI - Pulsatile arterial haemodynamics in heart failure.
AB - Due to the cyclic function of the human heart, pressure and flow in the
circulation are pulsatile rather than continuous. Addressing pulsatile
haemodynamics starts with the most convenient measurement, brachial pulse
pressure, which is widely available, related to development and treatment of
heart failure (HF), but often confounded in patients with established HF. The
next level of analysis consists of central (rather than brachial) pressures and,
more importantly, of wave reflections. The latter are closely related to left
ventricular late systolic afterload, ventricular remodelling, diastolic
dysfunction, exercise capacity, and, in the long-term, the risk of new-onset HF.
Wave reflection may also represent a suitable therapeutic target. Treatments for
HF with preserved and reduced ejection fraction, based on a reduction of wave
reflection, are emerging. A full understanding of ventricular-arterial coupling,
however, requires dedicated analysis of time-resolved pressure and flow signals,
which can be readily accomplished with contemporary non-invasive imaging and
modelling techniques. This review provides a summary of our current understanding
of pulsatile haemodynamics in HF.
PMID- 29947749
TI - The High-Quality Genome Sequence of the Oceanic Island Endemic Species Drosophila
guanche Reveals Signals of Adaptive Evolution in Genes Related to Flight and
Genome Stability.
AB - Drosophila guanche is a member of the obscura group that originated in the Canary
Islands archipelago upon its colonization by D. subobscura. It evolved into a new
species in the laurisilva, a laurel forest present in wet regions that in the
islands have only minor long-term weather fluctuations. Oceanic island endemic
species such as D. guanche can become model species to investigate not only the
relative role of drift and adaptation in speciation processes but also how
population size affects nucleotide variation. Moreover, the previous
identification of two satellite DNAs in D. guanche makes this species attractive
for studying how centromeric DNA evolves. As a prerequisite for its establishment
as a model species suitable to address all these questions, we generated a high
quality D. guanche genome sequence composed of 42 cytologically mapped scaffolds,
which are assembled into six super-scaffolds (one per chromosome). The
comparative analysis of the D. guanche proteome with that of twelve other
Drosophila species identified 151 genes that were subject to adaptive evolution
in the D. guanche lineage, with a subset of them being involved in flight and
genome stability. For example, the Centromere Identifier (CID) protein, directly
interacting with centromeric satellite DNA, shows signals of adaptation in this
species. Both genomic analyses and FISH of the two satellites would support an
ongoing replacement of centromeric satellite DNA in D. guanche.
PMID- 29947750
TI - Exercise unmasks distinct pathophysiologic features in heart failure with
preserved ejection fraction and pulmonary vascular disease.
AB - Aims: Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common
and associated with adverse outcomes in heart failure with preserved ejection
fraction (HFpEF). Little is known about the impact of PVD on the pathophysiology
of exercise intolerance. Methods and results: Heart failure with preserved
ejection fraction patients (n = 161) with elevated pulmonary capillary wedge
pressure (>=15 mmHg) at rest were classified into three groups: non-PH-HFpEF (n =
21); PH but no PVD (isolated post-capillary PH, IpcPH; n = 95); and PH with PVD
(combined post- and pre-capillary PH, CpcPH; n = 45). At rest, CpcPH-HFpEF
patients had more right ventricular (RV) dysfunction and lower pulmonary arterial
(PA) compliance compared to all other groups. While right atrial pressure (RAP)
and left ventricular transmural pressure (LVTMP) were similar in HFpEF with and
without PH or PVD at rest, CpcPH-HFpEF patients demonstrated greater increase in
RAP, enhanced ventricular interdependence, and paradoxical reduction in LVTMP
during exercise, differing from all other groups (P < 0.05). Lower PA compliance
was correlated with greater increase in RAP with exercise. During exercise, CpcPH
HFpEF patients displayed an inability to enhance cardiac output, reduction in
forward stroke volume, and blunted augmentation in RV systolic performance,
changes that were coupled with marked limitation in aerobic capacity. Conclusion:
Heart failure with preserved ejection fraction patients with PVD demonstrate
unique haemodynamic limitations during exercise that constrain aerobic capacity,
including impaired recruitment of LV preload due to excessive right heart
congestion and blunted RV systolic reserve. Interventions targeted to this
distinct pathophysiology require testing in patients with HFpEF and PVD.
PMID- 29947751
TI - Edoxaban therapy increases treatment satisfaction and reduces utilization of
healthcare resources: an analysis from the EdoxabaN vs. warfarin in subjectS
UndeRgoing cardiovErsion of atrial fibrillation (ENSURE-AF) study.
AB - Aims: The EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of atrial
fibrillation (ENSURE-AF) (NCT02072434) study was a multicentre prospective,
randomized, open-label, blinded-endpoint evaluation (PROBE) trial comparing
edoxaban with enoxaparin/warfarin followed by warfarin alone in 2199 non-valvular
atrial fibrillation patients undergoing electrical cardioversion and showed
comparable rates of bleeding and thromboembolism between treatments. This
prespecified ancillary analysis investigated the impact of edoxaban therapy on
treatment satisfaction and utilization of healthcare services. Methods and
results: The Perception of Anticoagulant Treatment Questionnaire (PACT-Q2) was
completed by study patients on Day 28 post-cardioversion. Higher scores represent
greater satisfaction. Healthcare resource utilizations were collected from
randomization to Day 28 post-cardioversion. Data from patients who received at
least one dose of study drugs were analysed. Patients treated with edoxaban were
more satisfied than enoxaparin/warfarin in both PACT-Q treatment satisfaction and
convenience scores (P < 0.001 for both). Differences in treatment satisfaction
scores were greater in patients who underwent non-transoesophageal
echocardiography (TOE)-guided cardioversion than in patients who underwent TOE
guided cardioversion. Edoxaban was associated with fewer clinic visits (4.75
visits vs. 7.60 visits; P < 0.001) and fewer hospital days (3.43 days vs. 5.41
days; P < 0.05). Rates of hospitalizations and emergency room visits were not
significantly different. Overall, edoxaban therapy was estimated to reduce
healthcare costs by ?107.73, ?437.92, ?336.75, and $246.32 per patient in German,
Spanish, Italian, and US settings, respectively. Conclusions: The convenience of
edoxaban therapy over warfarin in patients undergoing cardioversion may provide
greater treatment satisfaction and cost savings to the healthcare system.
PMID- 29947752
TI - The stringent response and Mycobacterium tuberculosis pathogenesis.
AB - During infection, the host restrains Mycobacterium tuberculosis (Mtb) from
proliferating by imposing an arsenal of stresses. Despite this onslaught of
attacks, Mtb is able to persist for the lifetime of the host, indicating that
this pathogen has substantial molecular mechanisms to resist host-inflicted
damage. The stringent response is a conserved global stress response in bacteria
that involves the production of the hyperphosphorylated guanine nucleotides ppGpp
and pppGpp (collectively called (p)ppGpp). (p)ppGpp then regulates a number of
cellular processes to adjust the physiology of the bacteria to promote survival
in different environments. Survival in the presence of host-generated stresses is
an essential quality of successful pathogens, and the stringent response is
critical for the intracellular survival of a number of pathogenic bacteria. In
addition, the stringent response has been linked to virulence gene expression,
persistence, latency and drug tolerance. In Mtb, (p)ppGpp synthesis is required
for survival in low nutrient conditions, long term culture and during chronic
infection in animal models, all indicative of a strict requirement for (p)ppGpp
during exposure to stresses associated with infection. In this review we discuss
(p)ppGpp metabolism and how this functions as a critical regulator of Mtb
virulence.
PMID- 29947753
TI - Comment on 'Meta-Analysis of the Association Between Anti-Tumour Necrosis Factor
Use and Lymphoma Risk in Patients With Inflammatory Bowel Disease: Methodological
Considerations'.
PMID- 29947754
TI - Primary prevention with the implantable cardioverter-defibrillator in high-risk
long-QT syndrome patients.
AB - Aims: Prospective data regarding the role of implantable cardioverter
defibrillator (ICD) for the primary prevention of sudden cardiac death in
patients with long QT syndrome (LQTS) is scarce. Herein, we explore the
prospective Rochester LQTS ICD registry to assess the risk for appropriate shock
in primary prevention in a real-world setting. Methods and results: We studied
212 LQTS patients that had ICD implantation for primary prevention. Best-subsets
proportional-hazards regression analysis was used to identify clinical variables
that were associated with the first appropriate shock. Conditional models of
Prentice, Williams, and Peterson were utilized for the analysis of recurrent
appropriate shocks. During a median follow-up of 9.2 +/- 4.9 years, there were 42
patients who experienced at least one appropriate shock and the cumulative
probability of appropriate shock at 8 years was 22%. QTc >= 550 ms [hazard ratio
(HR) 3.94, confidence interval (CI) 2.08-7.46; P < 0.001) and prior syncope on
beta-blockers (HR 1.92, CI 1.01-3.65; P = 0.047) were associated with increased
risk of appropriate shock. History of syncope while on beta-blocker treatment (HR
1.87, CI 1.28-2.72; P = 0.001), QTc 500-549 ms (HR 1.68, CI 1.10-2.81; P =
0.048), and QTc >= 550 ms (HR 3.66, CI 2.34-5.72; P < 0.001) were associated with
increased risk for recurrent appropriate shocks, while beta-blockers were not
protective (HR 1.03, CI 0.63-1.68, P = 0.917). LQT2 (HR 2.10, CI 1.22-3.61; P =
0.008) and multiple mutations (HR 2.87, CI 1.49-5.53; P = 0.002) were associated
with higher risk for recurrent shocks as compared with LQT1. Conclusion: In this
prospective ICD registry, we identified clinical and genetic variables that were
associated appropriate shock risk. These data can be used for risk stratification
in high-risk patients evaluated for primary prevention with ICD.
PMID- 29947755
TI - Reminders improve oral hygiene and adherence to appointments in orthodontic
patients: a systematic review and meta-analysis.
AB - Background: Reminders are implemented in healthcare services to increase
compliance with treatment and to decrease the rate of failed appointments. Their
effects in the provision of orthodontic care are not yet fully understood.
Objectives: The main objectives of this review were to assess the effectiveness
of reminder systems in improving oral hygiene (OH) and adherence to appointments
in orthodontic patients. Search methods: An unrestricted search was conducted in
six electronic databases and was supplemented by an extensive manual search up to
January 2018. Selection criteria: Only randomized controlled trials (RCTs)
evaluating the effectiveness of reminders in orthodontics were included. Data
collection and analysis: Two authors were independently involved in study
selection, data extraction, and bias assessment. A random-effects model with its
corresponding 95% confidence interval (CI) was generated for comparable outcomes.
Periodontal parameters were evaluated in the short term (1-3 months) and in the
long term (>3 months). Cochrane risk of bias tool was utilized for bias
assessment and the quality of the resultant evidence was graded. Additional
subgroup and sensitivity analyses were implemented. Results : Fourteen RCTs
involving 2078 participants met the inclusion criteria; five studies were
excluded from the quantitative synthesis due to high risk of bias. Small but
statistically significant standardized mean differences in the plaque index
scores were recorded favoring patients receiving reminders in the short-term (
0.38; 95% CI: -0.65 to -0.10) and in the long-term (-1.51; 95% CI: -2.72 to
0.30). Patients receiving reminders were less likely to miss their appointments
with a relative risk of (0.39; 95% CI: 0.22 to 0.70) and less likely to develop
white spot lesions (0.45; 95% CI: 0.31 to 0.65). Conclusions: There is moderate
to-high quality of evidence that reminders have a positive effect on OH and
adherence to appointments in orthodontic patients. These effects were
demonstrated in the short- and long-term. Future high-quality RCTs should be
designed with longer follow-up periods. Registration: PROSPERO (CRD42017084479).
Conflict of interest: None.
PMID- 29947756
TI - The transformics assay: first steps for the development of an integrated approach
to investigate the malignant cell transformation in vitro.
PMID- 29947757
TI - BMC3C: Binning Metagenomic Contigs using Codon usage, sequence Composition and
read Coverage.
AB - Motivation: Metagenomics investigates the DNA sequences directly recovered from
environmental samples. It often starts with reads assembly, which leads to
contigs rather than more complete genomes. Therefore, contig binning methods are
subsequently used to bin contigs into genome bins. While some clustering-based
binning methods have been developed, they generally suffer from problems related
to stability and robustness. Results: We introduce BMC3C, an ensemble clustering
based method, to accurately and robustly bin contigs by making use of DNA
sequence Composition, Coverage across multiple samples, and Codon usage. BMC3C
begins by searching the proper number of clusters and repeatedly applying the k
means clustering with different initializations to cluster contigs. Next, a
weight graph with each node representing a contig is derived from these clusters.
If two contigs are frequently grouped into the same cluster, the weight between
them is high, and otherwise low. BMC3C finally employs a graph partitioning
technique to partition the weight graph into subgraphs, each corresponding to a
genome bin. We conduct experiments on both simulated and real-world datasets to
evaluate BMC3C, and compare it with the state-of-the-art binning tools. We show
that BMC3C has an improved performance than these tools. To our knowledge, this
is the first time that the codon usage features and ensemble clustering are used
in metagenomic contig binning and lead to improved performance of binning
methods. Availability: The codes of BMC3C are available at
http://mlda.swu.edu.cn/codes.php?name=BMC3C. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29947759
TI - Corrigendum.
PMID- 29947758
TI - Uncovering the Genomic Origins of Life.
AB - The Origin of Life Domain (OLD) is the period during which life on Earth began.
Here, we derive and use a new phylogenetic algorithm to analyze Protein Families
in order to reconstruct the chronological steps by which the OLD evolved. During
this period, life began with the appearance of the fundamental components of life
such as RNAs, DNAs, amino acids, and membranes. Chronologically, the Origin of
Life preceded the Last Universal Common Ancestor, which then subsequently
engendered modern life on Earth. Our phylogenetic algorithm allows us to
explicitly answer previously unknown origin of life questions. Specifically, we
explain and illustrate our computational methods by reconstructing the rings
describing the evolution of the RNA and DNA worlds. We phylogenetically
reconstruct how the RNA and DNA worlds evolved, infer the origins and
chronological order of appearance of the first genetic codes, test whether the
Ribosomal RNA world preceded the Membrane world, and interpret these new findings
with respect to the experimental and theoretical origin of life studies by
others.
PMID- 29947760
TI - Placental weight and birthweight: the relations with number of daily cigarettes
and smoking cessation in pregnancy. A population study.
AB - Background: We studied associations of number of daily cigarettes in the first
trimester with placental weight and birthweight in women who smoked throughout
pregnancy, and in women who stopped smoking after the first trimester. Methods:
We included all women with delivery of a singleton in Norway (n = 698 891) during
1999-2014, by using data from the Medical Birth Registry of Norway. We assessed
dose-response associations by applying linear regression with restricted cubic
splines. Results: In total, 12.6% smoked daily in the first trimester, and 3.7%
stopped daily smoking. In women who smoked throughout pregnancy, placental weight
and birthweight decreased by number of cigarettes; however, above 11-12
cigarettes we estimated no further decrease (Pnon-linearity < 0.001). Maximum
decrease in placental weight in smokers compared with non-smokers was 18.2 g [95%
confidence interval (CI): 16.6 to 19.7], and for birthweight the maximum decrease
was 261.9 g (95% CI: 256.1 to 267.7). In women who stopped smoking, placental
weight was higher than in non-smokers and increased by number of cigarettes to a
maximum of 16.2 g (95% CI: 9.9 to 22.6). Birthweight was similar in women who
stopped smoking and non-smokers, and we found no change by number of cigarettes
(Pnon-linearity < 0.001). Conclusions: In women who smoked throughout pregnancy,
placental weight and birthweight decreased non-linearly by number of cigarettes
in the first trimester. In women who stopped smoking, placental weight was higher
than in non-smokers and increased linearly by number of cigarettes; birthweight
was almost similar to that of non-smokers.
PMID- 29947762
TI - Numero: a statistical framework to define multivariable subgroups in complex
population-based datasets.
AB - Large-scale epidemiological and population data provide opportunities to identify
subgroups of people who are at risk of disease or exposed to adverse
environments. Clustering algorithms are popular data-driven tools to identify
these subgroups; however, relying exclusively on algorithms may not produce the
best results if the dataset does not have a clustered structure. For this reason,
we propose a framework (the R-library Numero) that combines the self-organizing
map algorithm, permutation analysis for statistical evidence and a final expert
driven subgrouping step. We used Numero to define subgroups in two examples
without an obvious clustering structure: a biomedical dataset of kidney disease
and another dataset of community-level socioeconomic indicators. We benchmarked
the Numero subgroupings against popular clustering algorithms (principal
components, K-means and hierarchical clustering). The Numero subgroupings were
more intuitive and easier to interpret without losing mathematical quality.
Therefore, we expect Numero to be useful for exploratory analyses of population
based epidemiological datasets.
PMID- 29947761
TI - Readapting to DCV Infection without Wolbachia: Frequency Changes of Drosophila
Antiviral Alleles Can Replace Endosymbiont Protection.
AB - There is now ample evidence that endosymbionts can contribute to host adaptation
to environmental challenges. However, how endosymbiont presence affects the
adaptive trajectory and outcome of the host is yet largely unexplored. In
Drosophila, Wolbachia confers protection to RNA virus infection, an effect that
differs between Wolbachia strains and can be targeted by selection. Adaptation to
RNA virus infections is mediated by both Wolbachia and the host, raising the
question of whether adaptive genetic changes in the host vary with the
presence/absence of the endosymbiont. Here, we address this question using a
polymorphic D. melanogaster population previously adapted to DCV infection for 35
generations in the presence of Wolbachia, from which we removed the endosymbiont
and followed survival over the subsequent 20 generations of infection. After an
initial severe drop, survival frequencies upon DCV selection increased
significantly, as seen before in the presence of Wolbachia. Whole-genome
sequencing, revealed that the major genes involved in the first selection
experiment, pastrel and Ubc-E2H, continued to be selected in Wolbachia-free D.
melanogaster, with the frequencies of protective alleles being closer to fixation
in the absence of Wolbachia. Our results suggest that heterogeneity in Wolbachia
infection status may be sufficient to maintain polymorphisms even in the absence
of costs.
PMID- 29947764
TI - Einstein's brain: lost and found.
PMID- 29947763
TI - A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy
with high risk of sudden cardiac death in a large five-generation family.
AB - Aims: Characterization of the cardiac phenotype associated with the novel LMNA
nonsense mutation c.544C>T, p.Q182*, which we have identified in a large five
generation family. Methods and results: A family tree was constructed. Clinical
data [arrhythmia, syncope, sudden cardiac death (SCD), New York Heart Association
(NYHA) class] were collected from living and deceased family members. DNA of 23
living family members was analysed for mutations in LMNA. Additionally, dilated
cardiomyopathy multi-gene-panel testing and whole exome sequencing were performed
in some family members to identify potential phenotype-modifiers. In this five
generation family (n = 65), 17 SCDs occurred at 49.3 +/- 10.0 years. Furthermore,
we identified eight additional mutation-carriers, seven symptomatic (44 +/- 13
years), and one asymptomatic (44 years). First signs of disease [sinus
bradycardia with atrioventricular (AV)-block I degrees ] occurred at 36.5 +/- 8.1
years. Paroxysmal atrial fibrillation (AF) (onset at 41.8 +/- 5.7 years) rapidly
progressed to permanent AF (46.2 +/- 9.8 years). Subsequently, AV-conduction
worsened, syncope, pacemaker-dependence, and non-sustained ventricular
tachycardia (43.3 +/- 8.2 years) followed. Ventricular arrhythmia caused SCD in
patients without implantable cardioverter-defibrillator (ICD). Patients protected
by ICD developed rapidly progressive heart failure (45.2 +/- 10.6 years). A
different phenotype was seen in a sub-family in three patients with early onset
of rapidly decompensating heart failure and only minor prior arrhythmia-related
symptoms. One patient received high-urgency heart transplantation (HTX) at 32
years, while two died prior to HTX. One of them developed lethal peripartum
associated heart failure. Possible disease-modifiers were identified in this
'heart failure sub-family'. Conclusion: The novel LMNA nonsense mutation c.544C>T
causes a severe arrhythmogenic phenotype manifesting with high incidence of SCD
in most patients; and in one sub-family, a distinct phenotype with fast
progressing heart failure, indicating the need for early consideration of ICD
implantation and listing for heart-transplantation.
PMID- 29947765
TI - Expression of Mullerian-Inhibiting Substance/Anti-Mullerian Hormone Type II
Receptor in the Human Theca Cells.
AB - Context: Mullerian-inhibiting substance/anti-Mullerian hormone (MIS/AMH) is
produced in the ovarian granulosa cells, and it is believed to inhibit ovarian
folliculogenesis and steroidogenesis in women of reproductive age. Objective: To
investigate the expression of MIS/AMH type II receptor (MISRII/AMHRII) that binds
MIS/AMH in the ovaries of reproductive-age women; to identify the exact targets
of MIS/AMH. Design: Laboratory study using human ovarian tissue. Setting:
University hospital. Patients: Tissue samples from 25 patients who had undergone
ovarian surgery. Interventions: The segregation of ovarian granulosa and theca
cells by laser microdissection was followed by RT-PCR, analyzing MISRII/AMHRII
mRNA expression. Afterward, in situ hybridization and immunohistochemistry were
performed to determine the localization of MISRII/AMHRII mRNA and protein
expression. Main Outcome Measures: MISRII/AMHRII mRNA expression by RT-PCR, in
situ hybridization, and immunohistochemistry. Results: MISRII/AMHRII were
expressed in granulosa and theca cells of preantral and antral follicles. The
granulosa cells showed stronger MISRII/AMHRII expression than theca cells.
MISRII/AMHRII mRNA staining of granulosa and theca cells in large antral
follicles, early atretic follicles, and corpus luteum waned but were still
detected weakly, showing higher expression in theca cells than in granulosa
cells. However, MISRII/AMHRII protein in the granulosa layer of the atretic
follicle and corpus luteum could not be assessed. Conclusions: As MISRII/AMHRII
is expressed in both granulosa and theca cells, this indicates that MIS/AMH,
produced in the granulosa cells, is active in the theca cells as well. MIS/AMH is
most likely actively involved not only in the autocrine and endocrine processes
but also in the paracrine processes involving theca cells.
PMID- 29947766
TI - Fatigue - a symptom in endometriosis.
AB - STUDY QUESTION: Is fatigue a frequent symptom of endometriosis? SUMMARY ANSWER:
Fatigue is an underestimated symptom of endometriosis as it affects the majority
of women with endometriosis, but it is not widely discussed in literature. WHAT
IS KNOWN ALREADY: Fatigue can be a symptom of endometriosis causing major
distress impacting the daily activities and quality of life of women with
endometriosis. However, few studies with large sample sizes have investigated
fatigue as a symptom of endometriosis. STUDY DESIGN, SIZE, DURATION: The study
was designed as a multi-center matched case-control study. Recruitment took place
at hospitals and private practices in Switzerland, Germany and Austria between
2010 and 2016. Data was collected from 1120 women, 560 of them with
endometriosis. The women with endometriosis were matched to 560 control women in
regard to age +/-3 years and ethnic background. PARTICIPANTS/MATERIALS, SETTING,
METHODS: Diagnosis of women with endometriosis had to be surgically and
histologically confirmed. Surgical exclusion or absence of any endometriosis
identifying symptoms was required for control subjects. Materials included
surgical and histological reports as well as data retrieved from a self
administered questionnaire. This study focused on the symptom fatigue in
endometriosis. Relationships of variables were established by regression analysis
and associations were quantified as odds ratios. MAIN RESULTS AND THE ROLE OF
CHANCE: Frequent fatigue was experienced by a majority of women diagnosed with
endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in
endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001),
depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P
< 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was
independent of age, time since first diagnosis and stage of the disease.
LIMITATIONS, REASONS FOR CAUTION: Women with asymptomatic endometriosis cannot be
excluded in the control group which would lead to underestimation of our results.
The study's design allows no evaluation of causal effects. WIDER IMPLICATIONS OF
THE FINDINGS: As fatigue is experienced by numerous women with endometriosis, it
needs to be addressed in the discussion of management and treatment of the
disease. In addition to treating endometriosis, it would be beneficial to reduce
insomnia, depression, pain and occupational stress in order to better manage
fatigue. STUDY FUNDING/COMPETING INTEREST(s): There was no additional funding
received for this study and no conflict of interest. TRIAL REGISTRATION NUMBER:
ClinicalTrials.gov, NCT 02511626.
PMID- 29947768
TI - Association of Hypothyroidism With All-Cause Mortality: A Cohort Study in an
Older Adult Population.
AB - Context: Although hypothyroidism is associated with many comorbidities, the
evidence for its association with all-cause mortality in older adults is limited.
Objective: To evaluate the association between hypothyroidism and all-cause
mortality in older adults. Design: Population-based retrospective cohort study.
Setting: National Health Insurance Research Database in Taiwan. Patients: After
1:10 age/sex/index year matching, 2029 patients aged >=65 years who received a
new diagnosis of hypothyroidism between 2001 and 2011 and 20,290 patients without
hypothyroidism or other thyroid diseases were included in the hypothyroidism and
nonhypothyroidism cohorts, respectively. Main Outcome Measures: All-cause
mortality was defined as the primary outcome. Cox proportional hazards regression
models were used to calculate the hazard ratios of mortality. To further evaluate
the effect of thyroxine replacement therapy (TRT) on mortality, we divided
patients with hypothyroidism into two groups: patients who received TRT and those
who did not. Results: Hypothyroidism was associated with an increased risk of all
cause mortality [adjusted hazard ratio (aHR), 1.82; 95% CI, 1.68 to 1.98; P <
0.001]. Patients with hypothyroidism who received TRT had a lower risk of
mortality than patients who did not receive TRT (aHR, 0.57; 95% CI, 0.49 to 0.66;
P < 0.001). Similar results were obtained after further propensity score matching
in age-, sex-, and comorbidity-stratified analyses. Conclusions: Hypothyroidism
was independently associated with increased all-cause mortality in older adults.
In patients with hypothyroidism, TRT was associated with a lower risk of all
cause mortality.
PMID- 29947767
TI - High linear energy transfer carbon-ion irradiation increases the release of the
immune mediator high mobility group box 1 from human cancer cells.
AB - Anti-tumor immunity modulates the local effects of radiation therapy. High
mobility group box 1 (HMGB1) plays a pivotal role in activating antigen-specific
T-cell responses. Here, we examined the relationship between linear energy
transfer (LET) and HMGB1 release. We assessed the proportions of KYSE-70, HeLa
and SiHa cells surviving after carbon-ion (C-ion) beam irradiation with different
LET values, using a clonogenic assay. The D10, the dose at which 10% of cells
survived, was calculated using a linear-quadratic model. HMGB1 levels in the
culture supernatants of C-ion beam-irradiated tumor cells were assessed by enzyme
linked immunosorbent assay. The D10 doses for 13 keV/MUm of C-ion irradiation in
KYSE-70, HeLa and SiHa cells were 2.8, 3.9 and 4.1 Gy, respectively, whereas
those for 70 keV/MUm C-ion irradiation were 1.4, 1.9 and 2.3 Gy, respectively. We
found that 70 keV/MUm of C-ion irradiation significantly increased HMGB1 levels
in the culture supernatants of all cell lines 72 h after irradiation compared
with non-irradiated controls. Furthermore, 70 keV/MUm of C-ion irradiation
significantly increased HMGB1 levels in the culture supernatants of all cell
lines 72 h after irradiation compared with 13 keV/MUm. The results suggest that
HMGB1 release from several cancer cell lines increases with increased LET.
PMID- 29947769
TI - Off-pump mitral valve repair: is less really more?
PMID- 29947770
TI - Modeling dynamics for oncogenesis encompassing mutations and genetic instability.
AB - Tumorigenesis has been described as a multistep process, where each step is
associated with a genetic alteration, in the direction to progressively transform
a normal cell and its descendants into a malignant tumour. Into this work, we
propose a mathematical model for cancer onset and development, considering three
populations: normal, premalignant and cancer cells. The model takes into account
three hallmarks of cancer: self-sufficiency on growth signals, insensibility to
anti-growth signals and evading apoptosis. By using a nonlinear expression to
describe the mutation from premalignant to cancer cells, the model includes
genetic instability as an enabling characteristic of tumour progression.
Mathematical analysis was performed in detail. Results indicate that apoptosis
and tissue repair system are the first barriers against tumour progression. One
of these mechanisms must be corrupted for cancer to develop from a single mutant
cell. The results also show that the presence of aggressive cancer cells opens
way to survival of less adapted premalignant cells. Numerical simulations were
performed with parameter values based on experimental data of breast cancer, and
the necessary time taken for cancer to reach a detectable size from a single
mutant cell was estimated with respect to some parameters. We find that the rates
of apoptosis and mutations have a large influence on the pace of tumour
progression and on the time it takes to become clinically detectable.
PMID- 29947771
TI - Letter to the Editor: "p.Val804Met, the Most Frequent Pathogenic Mutation in RET,
Confers a Very Low Lifetime Risk of Medullary Thyroid Cancer".
PMID- 29947772
TI - Decreased Expression of Prox1 Is Associated With Postoperative Recurrence in
Crohn's Disease.
AB - Background: Prox1 is a transcription factor necessary for lymphangiogenesis and
lymphatic function. The aim of the study was to assess the correlation between
the expression of Prox1 and postoperative recurrence in Crohn's disease [CD].
Methods: Forty CD patients who underwent ileo-colonic resection were included.
Expression levels of Prox1 and D2-40 were detected using immunohistochemistry.
Expression levels of Prox1, VEGFR3, and VEGFC protein were also detected in fresh
CD specimens using western blotting and quantitative polymerase chain reaction [Q
PCR]. Endoscopic recurrence was used as the endpoint. Patients comprised two
groups: endoscopic recurrence [Group R+] and no endoscopic recurrence [Group R-].
Results: Prox1 protein expression was significantly higher in CD than in normal
tissues [p <0.05], as detected using both immunohistochemistry and western
blotting. Analysis of inter-relationships revealed significant correlation
between Prox1 expression and lymphatic vessel density [p <0.001, r = 0.823].
There was also significant correlation between Prox1 expression and the visceral
fat area [VFA] [p = 0.002, r = -0.469]. The Group R- patients had significantly
higher Prox1 expression than the Group R+ patients [21.08 +/- 1.61 versus 15.64
+/- 1.17, p = 0.011]. Also, the lymphatic vessel density value was lower in Group
R+ than in Group R- patients [6.02 +/- 0.39 versus 8.13 +/- 0.59, p = 0.004].
Moreover, there was a significant difference in the VFA between Group R- and
Group R+ patients [64.43 +/- 7.76 versus 90.44 +/- 6.11, p = 0.016]. In addition
to Prox1, VEGFC/VEGFR3 was found to increase, which was further confirmed using Q
PCR. Conclusions: Prox1 expression could be useful as a protective factor against
recurrence in CD patients. The therapeutic role of Prox1 may lead to improved
treatments.
PMID- 29947773
TI - Parental Decision-Making and Deaf Children: A Systematic Literature Review.
AB - Parents or caregivers of children who are deaf or hard of hearing are required to
make complex and rational decisions soon after the confirmation of hearing loss.
Ways of facilitating decision-making have been a focus within the healthcare
sector for two decades and shared decision-making is now widely viewed as the
standard for good clinical care. A systematic literature review was undertaken to
identify the extent to which the principles of shared decision-making and
informed choice have been implemented for parents when they make decisions
related to their children with permanent hearing loss. Five databases were
searched for peer-reviewed papers describing the results of original research
published from 2000 to 2017, yielding 37 relevant papers. Studies were reviewed
using the three phases of decision-making-information exchange, deliberation, and
implementation. Two decisions dominated these studies-implantable devices and
communication modality. Most papers dealt with decision-making in the context of
bilateral hearing loss, with only one study focusing on unilateral hearing loss.
The review identified gaps where further research is needed to ensure the lessons
learnt in the broader decision-making literature are implemented when parents
make decisions regarding their child who is deaf or hard of hearing.
PMID- 29947774
TI - Autophagy-Associated Proteins Control Ebola Virus Internalization Into Host
Cells.
AB - Ebola virus (EBOV) enters host cells by macropinocytosis, a poorly understood
process. Recent studies have suggested that cell factors involved in autophagy,
an evolutionally conserved pathway leading to the lysosomal degradation of
protein aggregates and organelles during cellular stress, also have roles in
macropinocytosis. Here, we demonstrate that autophagy-associated proteins are
required for trafficking of EBOV into the cell body. Depleting cells of beclin 1,
autophagy-related protein 7, or microtubule-associated protein 1A/B light chain
3B (LC3B) abolished EBOV uptake, owing to a block in vesicle formation at the
cell surface. Both LC3B-I and LC3B-II interacted with macropinocytic structures.
Our work indicates that, although various forms of LC3B possess an inherent
ability to associate with forming macropinosomes, LC3B-II is critical for
internalization of macropinocytic vesicles and, therefore, EBOV from the cell
surface.
PMID- 29947775
TI - Vitamin D and Inflammatory Bowel Disease: Mendelian Randomization Analyses in the
Copenhagen Studies and UK Biobank.
AB - Context: Vitamin D may be a modifiable risk factor for inflammatory bowel disease
(IBD). Objectives: We tested the hypothesis that plasma 25-hydroxyvitamin D
levels are causally associated with risk of Crohn disease (CD) and ulcerative
colitis (UC). Design, Setting, Patients, and Interventions: We used a Mendelian
randomization design to study 120,013 individuals from the Copenhagen City Heart
Study, the Copenhagen General Population Study, and a Copenhagen-based cohort of
patients with IBD. Of these, 35,558 individuals had plasma 25-hydroxyvitamin D
measurements available, and 115,110 were genotyped for rs7944926 and rs11234027
in DHCR7 and rs10741657 and rs12794714 in CYP2R1, all variants associated with
plasma 25-hydroxyvitamin D levels. We identified 653 cases of CD and 1265 cases
of UC, of which 58 and 113, respectively, had 25-hydroxyvitamin D measurements
available. We also included genetic data from 408,455 individuals from the UK
Biobank, including 1707 CD cases and 3147 UC cases. Main Outcome Measure: Hazard
ratios for higher plasma 25-hydroxyvitamin D levels. Results: The multivariable
adjusted hazard ratios for 10 nmol/L higher 25-hydroxyvitamin D level were 1.04
(95% CI: 0.93 to 1.16) for CD and 1.13 (95% CI: 1.06 to 1.21) for UC. A combined
25-hydroxyvitamin D allele score was associated with a 1.4-nmol/L increase in
plasma 25-hydroxyvitamin D level and hazard ratios of 0.98 (95% CI: 0.94 to 1.03)
for CD and 1.01 (95% CI: 0.97 to 1.05) for UC. Combining genetic data from the
Copenhagen studies and the UK Biobank, genetically determined vitamin D did not
appear to influence the risk of CD or UC. Conclusions: Our results do not support
a major role for vitamin D deficiency in the development of IBD.
PMID- 29947777
TI - Proteomic analysis of FOXP proteins reveals interactions between cortical
transcription factors associated with neurodevelopmental disorders.
PMID- 29947776
TI - The genome of tapeworm Taenia multiceps sheds light on understanding parasitic
mechanism and control of coenurosis disease.
AB - Coenurosis, caused by the larval coenurus of the tapeworm Taenia multiceps, is a
fatal central nervous system disease in both sheep and humans. Though treatment
and prevention options are available, the control of coenurosis still faces
presents great challenges. Here, we present a high-quality genome sequence of T.
multiceps in which 240 Mb (96%) of the genome has been successfully assembled
using Pacbio single-molecule real-time (SMRT) and Hi-C data with a N50 length of
44.8 Mb. In total, 49.5 Mb (20.6%) repeat sequences and 13, 013 gene models were
identified. We found that Taenia spp. have an expansion of transposable elements
and recent small-scale gene duplications following the divergence of Taenia from
Echinococcus, but not in Echinococcus genomes, and the genes underlying
environmental adaptability and dosage effect tend to be over-retained in the T.
multiceps genome. Moreover, we identified several genes encoding proteins
involved in proglottid formation and interactions with the host central nervous
system, which may contribute to the adaption of T. multiceps to its parasitic
life style. Our study not only provides insights into the biology and evolution
of T. multiceps, but also identifies a set of species-specific gene targets for
developing novel treatment and control tools for coenurosis.
PMID- 29947779
TI - Why Qualitative Research is Needed in Gerontology and How We Can Do It Better.
PMID- 29947778
TI - Surveillance for Heartland and Bourbon Viruses in Eastern Kansas, June 2016.
AB - In June 2016, we continued surveillance for tick-borne viruses in eastern Kansas
following upon a larger surveillance program initiated in 2015 in response to a
fatal human case of Bourbon virus (BRBV) (Family Orthomyxoviridae: Genus
Thogotovirus). In 4 d, we collected 14,193 ticks representing four species from
four sites. Amblyomma americanum (L.) (Acari: Ixodidae) accounted for nearly all
ticks collected (n = 14,116, 99.5%), and the only other species identified were
Amblyomma maculatum Koch (Acari: Ixodidae), Dermacentor variabilis (Say) (Acari:
Ixodidae) and Ixodes scapularis Say (Acari: Ixodidae). All ticks were tested for
both BRBV and Heartland virus (Family Bunyaviridae: Genus Phlebovirus) in 964
pools. Five Heartland virus positive tick pools were detected and confirmed by
real-time reverse transcription PCR (rRT-PCR), while all pools tested negative
for BRBV. Each Heartland positive pool was composed of 25 A. americanum nymphs
with positive pools collected at three different sites in Bourbon County. A.
americanum is believed to be the primary vector of both Heartland and BRBVs to
humans based upon multiple detections of virus in field-collected ticks, its
abundance, and its aggressive feeding behavior on mammals including humans.
However, it is possible that A. americanum encounters viremic vertebrate hosts of
BRBV less frequently than viremic hosts of Heartland virus, or that BRBV is less
efficiently passed among ticks by co-feeding, or less efficiently passed
vertically from infected female ticks to their offspring resulting in lower field
infection rates.
PMID- 29947781
TI - Mimics of Inflammatory Bowel Disease.
AB - Inflammatory bowel disease (IBD) may present with nonspecific symptoms and
diagnostic findings. Therefore, many diseases may mimic the clinical symptoms,
endoscopic findings, and histologic features of IBD. In this paper, we will
review mimics of IBD, dividing the diseases that can imitate IBD into
noninfectious and infectious causes. For each disease state, we will discuss the
clinical symptoms and endoscopic and histologic features. Finally, we will
discuss how to distinguish these distinct disorders from IBD.
PMID- 29947780
TI - Altered Plasma Amino Acids and Lipids Associated With Abnormal Glucose Metabolism
and Insulin Resistance in Older Adults.
AB - Context and Objectives: Glucose metabolism becomes progressively impaired with
older age. Fasting glucose and insulin resistance are risk factors for premature
death and other adverse outcomes. We aimed to identifying plasma metabolites
associated with altered glucose metabolism and insulin resistance in older
community-dwelling adults. Participants and Methods: A targeted metabolomics
approach was used to identify plasma metabolites associated with impaired fasting
plasma glucose, 2-hour plasma glucose on oral glucose tolerance testing, and
homeostatic model assessment insulin resistance (HOMA-IR) in 472 participants who
participated in the Baltimore Longitudinal Study of Aging, with a mean (SD) age
of 70.7 (9.9) years. Results: We measured 143 plasma metabolites. In ordinal
logistic regression analyses, using a false discovery rate of 5% and adjusting
for potential confounders, we found that alanine, glutamic acid, and proline were
significantly associated with increased odds of abnormal fasting plasma glucose.
Phosphatidylcholine (diacyl C34:4, alkyl-acyl C32:1, C32:2, C34:2, C34:3, and
C36:3) was associated with decreased odds of abnormal fasting plasma glucose.
Glutamic and acid phosphatidylcholine alkyl-acyl C34:2 were associated with
increased and decreased odds of 2-hour plasma glucose, respectively. Glutamic
acid was associated with increased odds of higher tertiles of HOMA-IR. Glycine;
phosphatidylcholine (diacyl C32:0, alkyl-acyl C32:1, C32:2, C34:1, C34:2, C34:3,
C36:2, C36:3, C40:5, C40:6, C42:3, C42:4, and C42:5); sphingomyelin C16:0, C24:1,
and C26:1; and lysophosphatidylcholine C18:1 were associated with decreased odds
of abnormal HOMA-IR. Conclusions: Targeted metabolomics identified four plasma
amino acids and 16 plasma lipid species, primarily containing polyunsaturated
fatty acids, that were associated with abnormal glucose metabolism and insulin
resistance in older adults.
PMID- 29947782
TI - No Correlation of Pancreatic Fat and beta-Cell Function in Young Women With and
Without a History of Gestational Diabetes.
AB - Context: Pancreatic steatosis may contribute to beta-cell dysfunction in type 2
diabetes (T2D), but data are controversial. Women who had gestational diabetes
mellitus (GDM) are at high risk for developing T2D. Objective: To examine the
association of pancreatic fat content with early/first-phase insulin secretion
(as markers of beta-cell function). Design: Cross-sectional analysis of a
subcohort of the monocentric, prospective cohort study titled Prediction,
Prevention, and Subclassification of Type 2 Diabetes. Setting: Ludwig Maximilians
University Hospital, Munich, Germany. Participants: Ninety-seven women, 3 to 16
months after pregnancy [41 normoglycemic women post-GDM, 19 women post-GDM with
pathological glucose metabolism, and 37 normoglycemic women after a normoglycemic
pregnancy (controls)]. Main Outcome Measures: Correlation of MRI-measured
pancreatic fat content with early insulin release in an oral glucose tolerance
test (OGGT) [insulin increment within the first 30 minutes of the OGTT (IR30)]
and first-phase insulin response (FPIR) in an intravenous glucose tolerance test
(n = 65), both adjusted for insulin sensitivity index (ISI). Results: Pancreatic
fat content did not correlate with IR30 and FPIR adjusted for ISI. It correlated
positively with body mass index, waist circumference, liver fat, and
intraabdominal fat volume. Conclusion: Pancreatic fat content does not correlate
with beta-cell function in a cohort of young women with different degrees of T2D
risk.
PMID- 29947783
TI - The novel fungal CYP51 inhibitor VT-1598 is efficacious alone and in combination
with liposomal amphotericin B in a murine model of cryptococcal meningitis.
AB - Objectives: Annual global deaths from cryptococcal meningitis (CM) are estimated
at 180 000 and mortality is as high as 30%, even with optimal therapy. VT-1598 is
a novel fungal CYP51 inhibitor with potent intrinsic antifungal activity against
Cryptococcus. We report here VT-1598's in vivo antifungal activity in a murine
model of CM. Methods: Single-dose plasma and brain pharmacokinetics in mice and
MIC for Cryptococcus neoformans H99 were determined prior to efficacy studies.
Short-course monotherapy and combination doses were explored with the endpoint of
brain fungal burden. A survival study was also conducted using monotherapy
treatment with fungal burden measured after a 6 day drug washout. Results: Oral
doses of VT-1598 had good plasma and brain exposure and resulted in significant
(P < 0.0001) and dose-dependent reductions in brain fungal burden, reaching a 6
log10 reduction. Unlike either positive drug control (fluconazole or liposomal
amphotericin B), both mid and high doses of VT-1598 reduced fungal burden to
below levels measured at the start of treatment. When VT-1598 was dosed in the
survival study, no VT-1598-treated animal succumbed to the infection. Whereas
fluconazole showed a 2.5 log10 increase in fungal burden after the 6 day washout,
the VT-1598 mid- and high-dose animals showed almost no regrowth (<0.5 log10). In
a separate fungal burden study using suboptimal doses of VT-1598 and liposomal
amphotericin B to probe for combination effects, each combination had a positive
effect relative to corresponding monotherapies. Conclusions: These pre-clinical
in vivo data strongly support clinical investigation of VT-1598 as a novel
therapy for this lethal infection.
PMID- 29947784
TI - Translational regulation in mycobacteria and its implications for pathogenicity.
AB - Protein synthesis is a fundamental requirement of all cells for survival and
replication. To date, vast numbers of genetic and biochemical studies have been
performed to address the mechanisms of translation and its regulation in
Escherichia coli, but only a limited number of studies have investigated these
processes in other bacteria, particularly in slow growing bacteria like
Mycobacterium tuberculosis, the causative agent of human tuberculosis. In this
Review, we highlight important differences in the translational machinery of M.
tuberculosis compared with E. coli, specifically the presence of two additional
proteins and subunit stabilizing elements such as the B9 bridge. We also consider
the role of leaderless translation in the ability of M. tuberculosis to establish
latent infection and look at the experimental evidence that translational
regulatory mechanisms operate in mycobacteria during stress adaptation,
particularly focussing on differences in toxin-antitoxin systems between E. coli
and M. tuberculosis and on the role of tuneable translational fidelity in
conferring phenotypic antibiotic resistance. Finally, we consider the
implications of these differences in the context of the biological adaptation of
M. tuberculosis and discuss how these regulatory mechanisms could aid in the
development of novel therapeutics for tuberculosis.
PMID- 29947785
TI - Parental socioeconomic status and risk of cerebral palsy in the child: evidence
from two Nordic population-based cohorts.
AB - Background: We investigated whether the risk of cerebral palsy (CP) in the child
varies by parents' socioeconomic status, in Denmark and Norway. Methods: We
included almost 1.3 million children born in Demark during 1981-2007 and 2.4
million children born in Norway during 1967-2007, registered in the Medical Birth
registries. Data on births were linked to Statistics Denmark and Norway to
retrieve information on parents' education and relationship status and, in
Denmark, also income. CP diagnoses were obtained from linkage with national
registries. We used multivariate log-binominal regression models to estimate
relative risk (RR) of CP according to parental socioeconomic status. Results:
There was a strong trend of decreasing risk of CP with additional education of
both the mother and the father. These trends were nearly identical for the two
parents, with a one-third reduction in risk for those with the highest education
compared with parents with the lowest education. When both parents had high
education, risk of CP was further reduced (RR 0.58, 0.53-0.63). Women with
partners had a reduction in risk (RR 0.79, 0.74-0.85) compared with single
mothers overall. Risk patterns were stable over time, across countries and within
spastic bilateral and unilateral CP. Household income was not associated with
risk of CP. Conclusions: Risk of CP in two Scandinavian countries was lower among
educated parents and mothers with a partner, but unrelated to income. Factors
underlying this stable association with education are unknown, but could include
differences in potentially modifiable lifestyle factors and health behaviours.
PMID- 29947786
TI - Objectively Measured Sedentary Behavior, Physical Activity, and Cardiometabolic
Risk in Hispanic Youth: Hispanic Community Health Study/Study of Latino Youth.
AB - Context: Time spent in moderate-to-vigorous physical activity (MVPA), but not in
sedentary behavior (SB), is related to cardiometabolic risk among non-Hispanic
white youth. Objective: Examine associations of SB and MVPA with cardiometabolic
risk factors among Hispanic/Latino youth. Design: Cross-sectional analysis.
Setting: Four US communities. Participants: Hispanic/Latino youth (N = 1,426)
ages 8 to 16 years. Measurements: Associations of MVPA and SB, measured using 7
day accelerometer data (independent variables), with markers of glucose and lipid
metabolism, inflammation, and endothelial function (dependent variables), were
assessed in multivariable linear regression models while adjusting for
sociodemographic characteristics and accelerometer wear time. Additional models
controlled for obesity measures. Results: SB comprised a mean (SD) of 75% (13%)
of accelerometer wear time; mean (SD) time of MVPA was 35 min/d (22 min/d).
Deleterious levels of high-density lipoprotein-cholesterol (HDL-C),
triglycerides, insulin resistance, C-reactive protein, and plasminogen activator
inhibitor-1 were associated with lower levels of MVPA and higher levels of SB
(all P < 0.05). Associations of MVPA with log-transformed triglyceride
concentrations (beta per 15-min/d increment, -0.039; SE, 0.018; P = 0.037) and SB
with HDL-C (beta per 30-min/d increment, -0.63; SE, 0.26; P = 0.018), but not
those with other markers, remained significant after adjusting for MVPA or SB and
further adjustment for body mass index and waist circumference. Higher SB
tertiles were associated with lower soluble receptor for advanced glycation end
products in fully adjusted models (P for trend = 0.037). Conclusions:
Physiological precursors of diabetes and cardiovascular disease were associated
with MVPA and SB among US Hispanic/Latino youth, a group that bears a
disproportionate burden of metabolic disorders.
PMID- 29947787
TI - Cardioplegia in paediatric cardiac surgery: a systematic review of randomized
controlled trials.
AB - OBJECTIVES: Cardioplegia is the primary method for myocardial protection during
cardiac surgery. We conducted a systematic review of randomized controlled trials
of cardioplegia in children to evaluate the current evidence base. METHODS: We
searched MEDLINE, CENTRAL and LILACS and manually screened retrieved references
and systematic reviews to identify all randomized controlled trials comparing
cardioplegia solutions or additives in children undergoing cardiac surgery
published in any language; secondary publications and those reporting inseparable
adult data were excluded. Two or more reviewers independently screened studies
for eligibility and extracted data; the Cochrane Risk of Bias tool was used to
assess for potential biases. RESULTS: We identified 26 trials randomizing 1596
children undergoing surgery; all were single-centre, Phase II trials, recruiting
few patients (median 48, interquartile range 30-99). The most frequent comparison
was blood versus crystalloid in 10 (38.5%) trials, and the most common end points
were biomarkers of myocardial injury (17, 65.4%), inotrope requirements (15,
57.7%) and length of stay in the intensive care unit (11, 42.3%). However, the
heterogeneity of patients, interventions and reported outcome measures prohibited
meta-analysis. Overall risk of bias was high in 3 (11.5%) trials, unclear in 23
(88.5%) and low in none. CONCLUSIONS: The current literature on cardioplegia in
children contains no late phase trials. The small size, inconsistent use of end
points and low quality of reported trials provide a limited evidence base to
inform practice. A core outcome set of clinically important, standardized,
validated end points for assessing myocardial protection in children should be
developed to facilitate the conduct of high-quality, multicentre trials. PROSPERO
registration: CRD42017080205.
PMID- 29947788
TI - Population mobility reductions associated with travel restrictions during the
Ebola epidemic in Sierra Leone: use of mobile phone data.
AB - Background: Travel restrictions were implemented on an unprecedented scale in
2015 in Sierra Leone to contain and eliminate Ebola virus disease. However, the
impact of epidemic travel restrictions on mobility itself remains difficult to
measure with traditional methods. New 'big data' approaches using mobile phone
data can provide, in near real-time, the type of information needed to guide and
evaluate control measures. Methods: We analysed anonymous mobile phone call
detail records (CDRs) from a leading operator in Sierra Leone between 20 March
and 1 July in 2015. We used an anomaly detection algorithm to assess changes in
travel during a national 'stay at home' lockdown from 27 to 29 March. To measure
the magnitude of these changes and to assess effect modification by region and
historical Ebola burden, we performed a time series analysis and a crossover
analysis. Results: Routinely collected mobile phone data revealed a dramatic
reduction in human mobility during a 3-day lockdown in Sierra Leone. The number
of individuals relocating between chiefdoms decreased by 31% within 15 km, by 46%
for 15-30 km and by 76% for distances greater than 30 km. This effect was highly
heterogeneous in space, with higher impact in regions with higher Ebola
incidence. Travel quickly returned to normal patterns after the restrictions were
lifted. Conclusions: The effects of travel restrictions on mobility can be large,
targeted and measurable in near real-time. With appropriate anonymization
protocols, mobile phone data should play a central role in guiding and monitoring
interventions for epidemic containment.
PMID- 29947789
TI - The impact of social housing on mental health: longitudinal analyses using
marginal structural models and machine learning-generated weights.
AB - Background: Social housing may provide an affordable and secure residential
environment, but has also been associated with stigma, poor housing conditions
and locational disadvantage. We examined the cumulative effect of additional
years, and tenure security (number of transitions in/out), of social housing on
mental health in a large cohort of lower-income Australians. Methods: We analysed
a longitudinal panel survey that annually collected information on tenure and
health from 2001 to 2013. To address the time-varying effect of previous health
on social housing occupancy, we used marginal structural models. Stabilized
inverse probabilities of treatment weights were generated using ensemble learning
to improve prediction. To address remaining residual imbalance across covariates,
double adjustment was made by additionally including baseline covariates in
models. Mental health was measured using the Mental Health Short-Form summary
measure of the SF-36 (MH), and psychological distress was measured using the
Kessler Psychological Distress Scale (K10). Results: People who had continuous
exposure to social housing had worse mental health on average than people
continuously occupying other tenures. The worst mental health outcomes, however,
were observed for people who made multiple transitions. Mental health
deteriorated and psychological distress increased with number of transitions: MH
1.04 [95% confidence interval (CI) -2.16; 0.09) and K10 0.56 (95% CI 0.12; 1.00).
Estimates are in the order of 6% (MH) and 9% (K10) of one standard deviation for
each measure. Conclusions: The more transitions people made in/out of social
housing, the greater the impact on mental health and psychological distress,
supporting the case for provision of more stable forms of social housing.
PMID- 29947790
TI - Reply to Tomsic et al.
PMID- 29947791
TI - RUNX2 mutation reduces osteogenic differentiation of dental follicle cells in
cleidocranial dysplasia.
AB - Disturbed permanent tooth eruption is common in cleidocranial dysplasia (CCD), a
skeletal disorder caused by heterozygous mutation of RUNX2, but the mechanism
underlying is still unclear. As it is well known that dental follicle cells
(DFCs) play a critical role in tooth eruption, the changed biological
characteristics of DFCs might give rise to disturbance of permanent tooth
eruption in CCD patients. Thus, primary DFCs from one CCD patient and normal
controls were collected to investigate the effect of RUNX2 mutation on the bone
remodeling activity of DFCs and explore the mechanism of impaired permanent tooth
eruption in this disease. Conservation and secondary structure analysis revealed
that the RUNX2 mutation (c.514delT, p.172fs) found in the present CCD patient was
located in the highly conserved RUNT domain and converted the structure of RUNX2.
After osteogenic induction, we found that the mineralised capacity of DFCs and
the expression of osteoblast-related genes, including RUNX2, ALP, OSX, OCN and
Col Ialpha1, in DFCs was severely interfered by the RUNX2 mutation found in CCD
patients. To investigate whether the osteogenic deficiency of DFCs from the CCD
patient can be rescued by RUNX2 restoration, we performed 'rescue' experiments.
Surprisingly, the osteogenic deficiency and the abnormal expression of osteoblast
associated genes in DFCs from the CCD patient were almost rescued by
overexpression of wild-type RUNX2 using lentivirus. All these findings indicate
that RUNX2 mutation can reduce the osteogenic capacity of DFCs through inhibiting
osteoblast-associated genes, thereby disturbing alveolar bone formation, which
serves as a motive force for tooth eruption. This effect may provide valuable
explanations and implications for the mechanism of delayed permanent tooth
eruption in CCD patients.
PMID- 29947792
TI - Mechanisms Underlying Exacerbation of Osmotic Nephrosis Caused by Pre-existing
Kidney Injury.
AB - Osmotic nephrosis, a disease caused by intravenous infusion of various fluids
such as hypertonic sucrose and isotonic polysaccharide-based plasma volume
expanders, exhibits specific histopathological features, including vacuolated and
swollen proximal tubules, ie, "clear tubules". Pre-existing kidney injury
exacerbates this condition, resulting in major clinical problems. However, the
underlying mechanisms are unclear. Animal models often yield results that are
directly translatable to humans. Therefore, in this study, we performed detailed
histopathological analyses of the formation of clear tubules in rats treated with
gentamicin or ischemia/reperfusion (IR) operation followed by dextran
administration. The results showed that clear tubules may originate from
regenerative tubules. Additionally, we classified regenerative tubules into 3
categories based on their development, with a particular focus on the middle and
late stages. Comprehensive microarray and real-time polymerase chain reaction
analyses of mRNA extracted from regenerative tubules at each stage using laser
microdissection revealed that regenerative tubules in the middle stage showed an
imbalance between dextran absorption and metabolism, resulting in accumulation of
dextran, particularly in the cytoplasm of the tubules. Overall, our findings
demonstrated that clear tubules originated from regenerated tubules and that
tubules at the middle stage became clear tubules because of an imbalance during
their development. This could explain why osmotic nephrosis is exacerbated in the
presence of kidney lesions.
PMID- 29947793
TI - A Case Series of Smallpox Vaccination-Associated Myopericarditis: Effects on
Safety and Readiness of the Active Duty Soldier.
AB - Myopericarditis following smallpox vaccination is a documented side effect with
increasing incidence since reestablishing mandatory vaccination for deploying
military personnel. After the ACAM2000 smallpox vaccine replaced the Dryvax
smallpox vaccine, the rate of myopericarditis increased 50-fold.We describe six
case reports of active duty soldiers who presented to the emergency department
complaining of chest pain shortly after receiving routine pre-deployment
vaccinations to include smallpox. All were hospitalized and became non-deployable
after developing smallpox vaccination-associated myopericarditis.Some cases of
smallpox vaccination-associated myopericarditis are diagnosed in soldiers in
austere environments, which have led to the soldier being removed from the
mission for months at a time. This can be avoided by having all soldiers who
receive the smallpox vaccine screened for clinical evidence of myopericarditis at
30 days after receiving the vaccine. Contributing to the increasing rate of
myopericarditis as well as the negative impact on soldier medical readiness, the
continued use of the current ACAM2000 smallpox vaccine should be monitored.
PMID- 29947795
TI - Drug Survival and Immunogenicity After Switching From Remicade to Biosimilar CT
P13 in Inflammatory Bowel Disease Patients: Two-year Follow-up of a Prospective
Observational Cohort Study.
AB - Background: The infliximab biosimilar has entered daily inflammatory bowel
disease (IBD) practice. However, real-life outcomes beyond 1 year after switching
are scarce. We aimed to investigate the long-term drug survival, immunogenicity,
and pharmacokinetics 2 years after switching to CT-P13 in IBD patients. Methods:
We performed a single-center prospective observational cohort study in all
Remicade-treated IBD patients who previously switched to CT-P13. We
systematically documented reasons for discontinuation, trough levels, and
antidrug antibodies to infliximab (ADAs) at baseline, week 16, week 52, and week
104. Clinical and biochemical disease activity (HBI, SCCAI, CRP) and adverse
events were registered. Results: Eighty-three patients were enrolled, 57 had
Crohn's disease, 24 had ulcerative colitis, and 2 were IBD-unclassified. At week
104, 55 of 83 (66%) patients remained on CT-P13, and 3 were lost to follow-up.
Reasons for discontinuation were loss of response (n = 10), adverse events (n =
8), and disease remission (n = 7). ADAs were present in 5/83 patients at baseline
(before switching), in 2 patients before week 52, and no subsequent ADAs were
detected until week 104. Median trough levels and clinical and biochemical
disease activity at baseline, week 16, week 52 and week 104 did not significantly
change. Conclusion: In a prospective cohort with >2-year follow-up, 66% of IBD
patients continued CT-P13 after switching from Remicade. Two new cases with ADAs
were observed in year 1, but subsequently no immunogenicity was detected. These
results are reassuring and suggest that switching to CT-P13 does not impact long
term clinical outcomes. 10.1093/ibd/izy227_video1izy227.video15802479819001.
PMID- 29947796
TI - The Association Between Cannabis Use and Aberrant Behaviors During Chronic Opioid
Therapy for Chronic Pain.
AB - Objective: Health care providers are likely to see an increase in the concomitant
use of cannabis and opioids, particularly with the increased liberalization and
ongoing research into the possible role of medical marijuana for chronic pain.
Recent literature reports a prevalence of concurrent use ranging from 8.9% to
31.8%. The primary aim of this study was to determine the relationship between
cannabis use and aberrant drug behaviors in noncancer pain patients receiving
chronic opioid therapy. Design: Retrospective chart review. Setting: Community
based, interdisciplinary pain management center. Subjects: Data from 209 patients
who were evaluated for a medication management program between October 1, 2011,
and January 1, 2014, and met inclusion criteria. Forty-four were positive for
cannabis in their initial random urine drug toxicology. Methods: Data from
electronic health records, including demographics, urine drug toxicology,
disability, opioid dose, opioid risk assessment data, and pain severity were
analyzed to examine differences among cannabis users and noncannabis users.
Results: Subjects with cannabis in their initial urine drug toxicology were more
likely to have a future occurrence of an opioid-related aberrancy (P < 0.001), be
male (P = 0.047), have a history of substance abuse (P = 0.013), and be enrolled
into a higher level of clinical monitoring of opioid medication use (P = 0.008).
No other associations with demographic and clinical variables reached statistical
significance. Conclusions: Concurrent use of cannabis and opioids by patients
with chronic pain appears to indicate higher risk for opioid misuse. Closer
monitoring for opioid-related aberrancy is indicated for this group of patients.
PMID- 29947794
TI - Efficient CRISPR/Cas9-mediated editing of trinucleotide repeat expansion in
myotonic dystrophy patient-derived iPS and myogenic cells.
AB - CRISPR/Cas9 is an attractive platform to potentially correct dominant genetic
diseases by gene editing with unprecedented precision. In the current proof-of
principle study, we explored the use of CRISPR/Cas9 for gene-editing in myotonic
dystrophy type-1 (DM1), an autosomal-dominant muscle disorder, by excising the
CTG-repeat expansion in the 3'-untranslated-region (UTR) of the human myotonic
dystrophy protein kinase (DMPK) gene in DM1 patient-specific induced pluripotent
stem cells (DM1-iPSC), DM1-iPSC-derived myogenic cells and DM1 patient-specific
myoblasts. To eliminate the pathogenic gain-of-function mutant DMPK transcript,
we designed a dual guide RNA based strategy that excises the CTG-repeat expansion
with high efficiency, as confirmed by Southern blot and single molecule real-time
(SMRT) sequencing. Correction efficiencies up to 90% could be attained in DM1
iPSC as confirmed at the clonal level, following ribonucleoprotein (RNP)
transfection of CRISPR/Cas9 components without the need for selective enrichment.
Expanded CTG repeat excision resulted in the disappearance of ribonuclear foci, a
quintessential cellular phenotype of DM1, in the corrected DM1-iPSC, DM1-iPSC
derived myogenic cells and DM1 myoblasts. Consequently, the normal intracellular
localization of the muscleblind-like splicing regulator 1 (MBNL1) was restored,
resulting in the normalization of splicing pattern of SERCA1. This study
validates the use of CRISPR/Cas9 for gene editing of repeat expansions.
PMID- 29947797
TI - Evidence for a Large Expansion and Subfunctionalization of Globin Genes in Sea
Anemones.
AB - The globin gene superfamily has been well-characterized in vertebrates, however,
there has been limited research in early-diverging lineages, such as phylum
Cnidaria. This study aimed to identify globin genes in multiple cnidarian
lineages, and use bioinformatic approaches to characterize the evolution,
structure, and expression of these genes. Phylogenetic analyses and in silico
protein predictions showed that all cnidarians have undergone an expansion of
globin genes, which likely have a hexacoordinate protein structure. Our protein
modeling has also revealed the possibility of a single pentacoordinate globin
lineage in anthozoan species. Some cnidarian globin genes displayed tissue and
development specific expression with very few orthologous genes similarly
expressed across species. Our phylogenetic analyses also revealed that eumetazoan
globin genes form a polyphyletic relationship with vertebrate globin genes.
Overall, our analyses suggest that a Ngb-like and GbX-like gene were most likely
present in the globin gene repertoire for the last common ancestor of
eumetazoans. The identification of a large-scale expansion and
subfunctionalization of globin genes in actiniarians provides an excellent
starting point to further our understanding of the evolution and function of the
globin gene superfamily in early-diverging lineages.
PMID- 29947799
TI - Pharmacokinetics of intravenous and nebulized gentamicin in critically ill
patients.
AB - Objectives: Optimal dosing for nebulized gentamicin is unknown. We compared the
pulmonary and systemic pharmacokinetics (PK) of gentamicin following intravenous
and nebulized administration in mechanically ventilated patients. Methods: Twelve
critically ill male patients with ventilator-associated pneumonia received a 30
min intravenous infusion of 8 mg/kg gentamicin , followed 48 h afterwards by the
same dose nebulized. Blood samples were collected immediately before and until 24
h after intravenous and nebulized administration; mini-bronchoalveolar lavages
(mini-BALs) were performed at 3 and 7 h or 5 and 10 h (six patients each) after
each intravenous and nebulized administration. The PK analysis was conducted
using a population approach. Results: After intravenous administration,
concentrations of gentamicin measured in epithelial lining fluid (ELF) were very
variable, and overall in the same range of magnitude (from 0.3 to 28 mg/L) as in
plasma. After nebulization, gentamicin concentrations were much higher (~3800
fold) in ELF than in plasma. The average systemic bioavailability of nebulized
gentamicin was estimated to be 5%, with considerable inter-individual
variability. Compared with intravenous administration, after nebulization the
exposure (expressed as AUC) to gentamicin was 276-fold greater in ELF and 18-fold
lower in plasma. Conclusions: Compared with intravenous administration,
nebulization of gentamicin in patients with ventilator-associated pneumonia
provides higher pulmonary concentrations and lower systemic concentrations but
the inter-individual variability is large.
PMID- 29947798
TI - Bacillus subtilis RarA modulates replication restart.
AB - The ubiquitous RarA/Mgs1/WRNIP protein plays a crucial, but poorly understood
role in genome maintenance. We show that Bacillus subtilis RarA, in the apo form,
preferentially binds single-stranded (ss) over double-stranded (ds) DNA. SsbA
bound to ssDNA loads RarA, and for such recruitment the amphipathic C-terminal
domain of SsbA is required. RarA is a DNA-dependent ATPase strongly stimulated by
ssDNA-dsDNA junctions and SsbA, or by dsDNA ends. RarA, which may interact with
PriA, does not stimulate PriA DNA unwinding. In a reconstituted PriA-dependent
DNA replication system, RarA inhibited initiation, but not chain elongation. The
RarA effect was not observed in the absence of SsbA, or when the host-encoded
preprimosome and the DNA helicase are replaced by proteins from the SPP1 phage
with similar function. We propose that RarA assembles at blocked forks to
maintain genome integrity. Through its interaction with SsbA and with a
preprimosomal component, RarA might impede the assembly of the replicative
helicase, to prevent that recombination intermediates contribute to pathological
DNA replication restart.
PMID- 29947800
TI - Specialty Choices, Practice Characteristics, and Long-term Outcomes of Two
Cohorts of USUHS Medical School Graduates Compared with National Data.
AB - Introduction: The education of health professionals and the assessment of their
long-term goals are essential. Additionally, in the military health system (MHS),
such programs also have the goals of improving readiness, providing high-quality
care and meeting the needs and challenges of the MHS. The Uniformed Services
University F. Edward Hebert School of Medicine (USUHS) has existed for over 40
years and the assessment of the longer term outcomes of its medical school
graduates is an important endeavor. The purpose of this study is to describe the
relationship of USUHS on the care in the MHS by reporting specialty choices,
practice characteristics and locations of two consecutive cohorts of USUHS
graduates and to compare these cohort findings with national data. Two cohorts
were chosen as the first cohort has reached retirement and we sought to describe
the impact of our graduates following their military service commitment.
Materials and Methods: We performed a retrospective analysis of our graduates
(1980-2009) using data obtained from the American Medical Association Physician
Masterfile in two 15-year cohorts. USU graduate data are described and compared
with national allopathic medical school data in order to explore USUHS graduates'
practice characteristics and how these contrast with national data. Results:
Family medicine was the most commonly identified primary care specialty across
both USUHS cohorts. Other primary care specialties such as Internal Medicine and
Pediatrics became more popular among USUHS graduates over time. There were a
lower percentage of inactive USUHS graduates from the 1980-1994 cohorts than the
U.S. national sample (3.23% vs. 3.98%). The proportion of USUHS graduates working
in an office-based practice increased from 34.8% (1980-1994) to 43.6% (1995-2009)
yet still was lower than U.S. national data (1980-1994: 73.5%; 1995-2009: 73.8%).
The type of practice in which the majority of USUHS and national graduates were
involved was direct patient care (over 70% of the population). Practice locations
for medical school graduates included all 50 states. Furthermore, though several
states such as Mississippi, Nevada, South Carolina, and Utah were among the top
20 practice locations among USUHS graduates, they did not appear among the top 20
practicing states for U.S. graduates. Conclusions: USUHS can play a major role by
training health care professionals needed to meet the large health care strategic
goals of a transforming military health system. A high percentage of USUHS
graduates had significant changes in practice characteristics over time, are
staying in practice for longer time compared with U.S. graduates, and practice in
all 50 states including those that are underserved.
PMID- 29947801
TI - An FRMD4B variant suppresses dysplastic photoreceptor lesions in models of
enhanced S-cone syndrome and of Nrl deficiency.
AB - Photoreceptor dysplasia, characterized by formation of folds and (pseudo
)rosettes in the outer retina, is associated with loss of functional nuclear
receptor subfamily 2 group E member 3 (NR2E3) and neural retina leucine-zipper
(NRL) in both humans and mice. A sensitized chemical mutagenesis study to
identify genetic modifiers that suppress photoreceptor dysplasia in
Nr2e3rd7mutant mice identified line Tvrm222, which exhibits a normal fundus
appearance in the presence of the rd7 mutation. The Tvrm222 modifier of
Nr2e3rd7/rd7 was localized to Chromosome 6 and identified as a missense mutation
in the FERM domain containing 4B (Frmd4b) gene. The variant is predicted to cause
the substitution of a serine residue 938 with proline (S938P). The Frmd4bTvrm222
allele was also found to suppress outer nuclear layer (ONL) rosettes in Nrl-/-
mice. Fragmentation of the external limiting membrane (ELM), normally observed in
rd7 and Nrl-/-mouse retinas, was absent in the presence of the Frmd4bTvrm222
allele. FRMD4B, a binding partner of cytohesin 3, is proposed to participate in
cell junction remodeling. Its biological function in photoreceptor dysplasia has
not been previously examined. In vitro experiments showed that the FRMD4B938P
variant fails to be efficiently recruited to the cell surface upon insulin
stimulation. In addition, we found a reduction in protein kinase B
phosphorylation and increased levels of cell junction proteins, Catenin beta 1
and tight junction protein 1, associated with the cell membrane in Tvrm222
retinas. Taken together, this study reveals a critical role of FRMD4B in
maintaining ELM integrity and in rescuing morphological abnormalities of the ONL
in photoreceptor dysplasia.
PMID- 29947802
TI - Targeted Pregnancy and Human Immunodeficiency Virus Prevention Risk-Reduction
Counseling for Young Women: Lessons Learned from Biomedical Prevention Trials.
AB - Background: Women enrolled in human immunodeficiency virus (HIV) prevention
efficacy trials receive counseling on prevention of HIV, sexually transmitted
infections (STIs), and pregnancy during every visit. Incident pregnancy has an
impact on efficacy outcomes. Incidence rates of pregnancy and HIV/STIs among
women who became pregnant and associated risk factors were assessed. Methods:
Data from 9165 women participating in HIV prevention trials in KwaZulu-Natal,
South Africa from 2002-2012 were combined. Demographic and behavioral predictors
of incidence pregnancy and incidence HIV and STIs were determined using Cox
regression models. Results: Overall pregnancy incidence was 9.6 per 100 person
year (py) (95% confidence interval [Cl], 9.1-10.3). Human immunodeficiency virus
incidence among pregnant women was 5.93 per 100 py (95% Cl, 4.73-7.44). Incidence
of STIs among pregnant women for Chlamydia trachomatis, Trichomonas vaginalis,
Neisseria gonorrhoeae, and Treponema pallidum (syphilis) were 10.87, 7.42, 3.92,
and 1.43 per 100 py, respectively. In the adjusted analyses, we observed
overlapping risk factors for HIV acquisition during pregnancy, ie, young age, not
married/not cohabitating, and low parity. The risk of pregnancy and HIV
acquisition is more than 3 times higher among young women (<20 years of age).
Conclusions: We identified overlapping risk factors for pregnancy and HIV
incidence, suggesting an urgent need for appropriate, targeted, individual
centred counseling for women participating in HIV prevention trials.
PMID- 29947803
TI - Quokka: a comprehensive tool for rapid and accurate prediction of kinase family
specific phosphorylation sites in the human proteome.
AB - Motivation: Kinase-regulated phosphorylation is a ubiquitous type of post
translational modification (PTM) in both eukaryotic and prokaryotic cells.
Phosphorylation plays fundamental roles in many signalling pathways and
biological processes, such as protein degradation and protein-protein
interactions. Experimental studies have revealed that signalling defects caused
by aberrant phosphorylation are highly associated with a variety of human
diseases, especially cancers. In light of this, a number of computational methods
aiming to accurately predict protein kinase family-specific or kinase-specific
phosphorylation sites have been established, thereby facilitating
phosphoproteomic data analysis. Results: In this work, we present Quokka, a novel
bioinformatics tool that allows users to rapidly and accurately identify human
kinase family-regulated phosphorylation sites. Quokka was developed by using a
variety of sequence scoring functions combined with an optimized logistic
regression algorithm. We evaluated Quokka based on well-prepared up-to-date
benchmark and independent test datasets, curated from the Phospho.ELM and UniProt
databases, respectively. The independent test demonstrates that Quokka improves
the prediction performance compared with state-of-the-art computational tools for
phosphorylation prediction. In summary, our tool provides users with high-quality
predicted human phosphorylation sites for hypothesis generation and biological
validation. Availability: The Quokka webserver and datasets are freely available
at http://quokka.erc.monash.edu/. Supplementary information: Supplementary data
are available at Bioinformatics online.
PMID- 29947804
TI - Classification of First-Episode Schizophrenia Using Multimodal Brain Features: A
Combined Structural and Diffusion Imaging Study.
AB - Recent neuroanatomical pattern recognition studies have shown some promises for
developing an objective neuroimaging-based classification related to
schizophrenia. This study explored the feasibility of reliably identifying
schizophrenia using single and multimodal multivariate neuroimaging features.
Multiple brain measures including regional gray matter (GM) volume, cortical
thickness, gyrification, fractional anisotropy (FA), and mean diffusivity (MD)
were extracted using fully automated procedures. We used Gradient Boosting
Decision Tree to identify the most frequently selected features of each set of
neuroanatomical metric and fused multimodal measures. The current classification
model was trained and validated based on 98 patients with first-episode
schizophrenia (FES) and 106 matched healthy controls (HCs). The classification
model was trained and tested in an independent dataset of 54 patients with FES
and 48 HCs using imaging data acquired on a different magnetic resonance imaging
scanner. Using the most frequently selected features from fused structural and
diffusion tensor imaging metrics, a classification accuracy of 75.05% was
achieved, which was higher than accuracy derived from a single imaging metric.
Most prominent discriminative features included cortical thickness of left
transverse temporal gyrus and right parahippocampal gyrus, the FA of left
corticospinal tract and right external capsule. In the independent cohort,
average accuracy was 76.54%, derived from combined features selected from
cortical thickness, gyrification, FA, and MD. These features characterized by GM
abnormalities and white matter disruptions have discriminative power with respect
to the underlying pathological changes in the brain of individuals having
schizophrenia. Our results further highlight the potential advantage of
multimodal data fusion for identifying schizophrenia.
PMID- 29947805
TI - Unstructured clinical documentation reflecting cognitive and behavioral
dysfunction: toward an EHR-based phenotype for cognitive impairment.
AB - Despite increased risk for negative outcomes, cognitive impairment (CI) is
greatly under-detected during hospitalization. While automated EHR-based
phenotypes have potential to improve recognition of CI, they are hindered by
widespread under-diagnosis of underlying etiologies such as dementia-limiting the
utility of more precise structured data elements. This study examined
unstructured data on symptoms of CI in the acute-care EHRs of hip and stroke
fracture patients with dementia from two hospitals. Clinician reviewers
identified and classified unstructured EHR data using standardized criteria.
Relevant narrative text was descriptively characterized and evaluated for key
terminology. Most patient EHRs (90%) had narrative text reflecting cognitive
and/or behavioral dysfunction common in CI that were reliably classified (kappa
0.82). The majority of statements reflected vague descriptions of
cognitive/behavioral dysfunction as opposed to diagnostic terminology. Findings
from this preliminary derivation study suggest that clinicians use specific
terminology in unstructured EHR fields to describe common symptoms of CI. This
terminology can inform the design of EHR-based phenotypes for CI and merits
further investigation in more diverse, robustly characterized samples.
PMID- 29947806
TI - Maternal Serum Cobalamin at 18 Weeks of Pregnancy Predicts Infant Cobalamin
Status at 6 Months-A Prospective, Observational Study.
AB - Background: An adequate maternal cobalamin status is crucial for fetal and infant
neurodevelopment. Pregnancy-induced physiologic changes make evaluation of
maternal cobalamin status in pregnancy difficult. Objective: We have investigated
maternal cobalamin status during pregnancy in order to establish a maternal
cobalamin concentration which secures an optimal infant cobalamin status during
the first 6 mo of life. Methods: In an observational, prospective study, markers
of cobalamin status including serum cobalamin, plasma total homocysteine (tHcy),
and plasma methylmalonic acid (MMA) were assessed in healthy pregnant women (n =
114) from week 18 of pregnancy through 6 mo postpartum and related to infant
cobalamin status at 6 mo. Healthy, never-pregnant women aged 18-40 y (n = 123)
were included as controls. Results: Compared to controls, all markers of
cobalamin status were lower in pregnant women. Median serum cobalamin
concentration progressively decreased from week 18 to week 36 of pregnancy (356
to 302 pmol/L, P < 0.001) and increased by >40% by 6 wk postpartum (518 pmol/L).
The metabolic markers increased from week 18 of pregnancy to 6 wk postpartum:
median plasma tHcy 3.9 to 7.7 MUmol/L (P < 0.001), and MMA 0.13 to 0.17 MUmol/L
(P < 0.001). The serum cobalamin concentration of infants at age 6 mo correlated
with maternal serum cobalamin concentration during pregnancy and postpartum (rho
= 0.36-0.55, P < 0.001). A maternal serum cobalamin concentration <394 pmol/L
during week 18 of pregnancy was associated with an increased risk (OR: 4.2; 95%
CI: 1.5, 11.5) of infant biochemical cobalamin deficiency at 6 mo (defined as
tHcy >=6.5 MUmol/L). Conclusions: The maternal serum cobalamin concentration in
early pregnancy is a strong predictor for later maternal and infant cobalamin
status. To secure an optimal infant cobalamin status during the first 6 mo of
life, we recommend a maternal serum cobalamin concentration >394 pmol/L at week
18 of pregnancy. This should be confirmed in an intervention study. This trial
was registered at clinicaltrials.gov as NCT03272022.
PMID- 29947807
TI - Biology, Thermal Requirements, and Estimation of the Number of Generations of
Hypothenemus hampei (Ferrari, 1867) (Coleoptera: Curculionidae) in the State of
Sao Paulo, Brazil.
AB - Coffee culture, one of the main agricultural activities in Brazil, has undergone
recent negative impacts due to unfavorable climate conditions, with a subnormal
rainy period and increased temperatures during the second half of 2015. The
coffee berry borer Hypothenemus hampei (Ferrari, 1867) (Coleoptera:
Curculionidae) is one of the main insect pests of coffee crops worldwide. The
present research aimed to determine the climate zones for coffee berry borer in
the state of Sao Paulo, based on its thermal requirements. The results showed
that the mean biological development time of H. hampei was affected by
temperature, completing its life cycle more rapidly in increased temperatures
until the 30 degrees C threshold temperature, and more slowly above this
temperature. Development time (egg-adult) was inversely related to temperature in
the range between 18 and 32 degrees C. The temperature threshold (Tt) was 13.9
degrees C and the thermal constant (K) was 299 degree-days. These laboratory
estimates of thermal requirements and the Geographic Information System (GIS)
were used to generate insect life span distribution maps for Sao Paulo. In this
state, the coffee berry borer can produce 5.09-10.53 generations annually. Higher
pest incidences should coincide with both temperature increases and the
availability of coffee fruit for infestation. The data obtained can be used to
estimate the monthly and yearly number of generations of this pest, for use in
integrated pest management programs.
PMID- 29947808
TI - Novel jack-in-the-box effector of the barley powdery mildew pathogen?
PMID- 29947809
TI - Nitric oxide sensor proteins with revolutionary potential.
PMID- 29947810
TI - The Role of Fibrinogen-Like Protein 2 on Immunosuppression and Malignant
Progression in Glioma.
AB - Background: Virtually all low-grade gliomas (LGGs) will progress to high-grade
gliomas (HGGs), including glioblastoma, the most common malignant primary brain
tumor in adults. A key regulator of immunosuppression, fibrinogen-like protein 2
(FGL2), may play an important role in the malignant transformation of LGG to HGG.
We sought to determine the mechanism of FGL2 on tumor progression and to show
that inhibiting FGL2 expression had a therapeutic effect. Methods: We analyzed
human gliomas that had progressed from low- to high-grade for FGL2 expression. We
modeled FGL2 overexpression in an immunocompetent genetically engineered mouse
model to determine its effect on tumor progression. Tumors and their associated
microenvironments were analyzed for their immune cell infiltration. Mice were
treated with an FGL2 antibody to determine a therapeutic effect. Statistical
tests were two-sided. Results: We identified increased expression of FGL2 in
surgically resected tumors that progressed from low to high grade (n = 10). The
Cancer Genome Atlas data showed that LGG cases with overexpression of FGL2 (n =
195) had statistically significantly shorter survival (median = 62.9 months)
compared with cases with low expression (n = 325, median = 94.4 months, P <
.001). In a murine glioma model, HGGs induced with FGL2 exhibited a mesenchymal
phenotype and increased CD4+ forkhead box P3 (FoxP3)+ Treg cells, implicating
immunosuppression as a mechanism for tumor progression. Macrophages in these
tumors were skewed toward the immunosuppressive M2 phenotype. Depletion of Treg
cells with anti-FGL2 statistically significantly prolonged survival in mice
compared with controls (n = 11 per group, median survival = 90 days vs 62 days, P
= .004), shifted the phenotype from mesenchymal HGG to proneural LGG, and
decreased M2 macrophage skewing. Conclusions: FGL2 facilitates glioma progression
from low to high grade. Suppressing FGL2 expression holds therapeutic promise for
halting malignant transformation in glioma.
PMID- 29947811
TI - Assessing qualitatively the impact of gout on sleep: any sleep was a dream far
away until the gout flare resolved.
PMID- 29947812
TI - Serum Zinc Concentrations in the US Population Are Related to Sex, Age, and Time
of Blood Draw but Not Dietary or Supplemental Zinc.
AB - Background: Serum zinc concentration is used to assess the zinc status of
populations. Cutoffs for serum zinc were developed on the basis of data from the
second NHANES (1976-1980). Objective: The objective of this study was to evaluate
serum zinc concentrations in the US population and to determine factors affecting
serum zinc with the use of NHANES 2011-2014. Methods: Serum zinc was determined
in males and females aged >=6 y with the use of NHANES 2011-2014 (n = 4347).
Dietary zinc intake was determined, and factors affecting serum zinc were
identified with the use of regression models adjusting for sex, age, fasting
status, and time of blood draw. ORs were calculated to identify factors
associated with the risk of being below the serum zinc cutoff, and the prevalence
of low serum zinc in the US was calculated. P < 0.01 was considered significant.
Results: Mean +/- SE serum zinc concentrations in males and females were 84.9 +/-
0.8 and 80.6 +/- 0.6 MUg/dL, respectively (P < 0.0001). Regression models with
serum zinc as the dependent variable indicated that afternoon and evening blood
draws (beta = -9.7 and -15.3; P < 0.0001) were negatively associated with serum
zinc concentrations and serum albumin (beta = 16.1; P < 0.0001) and hemoglobin
(beta = 1.0; P = 0.0048) were positively associated with serum zinc
concentrations. Hypoalbuminemia (OR = 11.2; 99% CI: 3.4, 37.3), anemia in females
(OR: 3.4; 99% CI: 1.7, 6.9), and pregnancy (OR: 9.6; 99% CI: 2.9, 31.9) increased
the odds of being below the serum zinc cutoff (P < 0.0001 for all). Zinc from
diet or supplements did not affect serum zinc (P > 0.01). Approximately 3.8% of
children (<10 y), 8.6% of males (>=10 y), and 8.2% of females (>=10 y) were below
the serum zinc cutoff. Conclusions: Factors such as sex, age, and time of blood
draw should be considered when using serum zinc concentration to determine the
zinc status of a population. Caution is advised when interpreting serum zinc
concentration in populations with a high prevalence of hypoalbuminemia or anemia.
This trial was registered at http://www.isrctn.com as ISRCTN96013840.
PMID- 29947813
TI - Susceptibility Vessel Sign and Cardioembolic Etiology in the THRACE Trial.
AB - PURPOSE: The susceptibility vessel sign (SVS) has been described on gradient echo
(GRE) magnetic resonance imaging (MRI) in acute ischemic stroke patients by large
vessel occlusion. The presence of SVS (SVS+) was associated with treatment
outcome and stroke etiology with conflicting results. Based on multicenter data
from the THRombectomie des Arteres CErebrales (THRACE) study, we aimed to
determine if the association between SVS and cardioembolic etiology (CE) was
independent of GRE sequence parameters. MATERIAL AND METHODS: Patients with a
pretreatment brain GRE sequence were identified. Logistic regression tested the
association between SVS+, CE, time from onset to imaging and GRE sequence
parameters (e.g. echo time, voxel size, field strength). We calculated the
sensitivity, specificity, positive and negative predictive values (PPV and NPV)
for the SVS to predict a stroke from a CE. RESULTS: An SVS+ was observed in 237
out of 287 (83%) patients. In the univariate analysis, there was a significant
association between SVS+ and a CE with an odds ratio (OR) and 95% confidence
interval (95% CI) of 2.10 (1.02-4.29), respectively (p = 0.04) but not with GRE
sequence parameters. In multivariate analysis, there was an independent
relationship between SVS+ and CE (OR [95% CI]: 2.14 [1.02-4.45], p = 0.04).
Sensitivity and specificity of SVS+ to predict CE were 0.89 and 0.21,
respectively. The PPV and NPV of SVS+ were 0.44 and 0.78, respectively.
CONCLUSION: The presence of SVS is associated to CE, independent of GRE sequence
parameters. While the specificity and the PPV of the sign were low, CE seems less
likely in the absence of an SVS.
PMID- 29947814
TI - Correlation between oral health-related quality of life and orthodontic treatment
need in children and adolescents-a prospective interdisciplinary multicentre
cohort study.
AB - PURPOSE: Oral health-related quality of life (OHRQoL) is a construct for
assessing the self-perceived oral health of patients. The aim of this study was
to investigate the correlation between OHRQoL and orthodontic treatment need in
consideration of demographic and psychological factors. PATIENTS AND METHODS:
This multicentre study included 250 patients with an indication for orthodontic
diagnostics. In cooperation with the Institute of Clinical Psychology at the
University of Wurzburg, validated and internationally acknowledged questionnaires
were selected to assess OHRQoL (COHIP-G19) and health-related quality of life
(HRQOL). Self-esteem and behavioural problems were taken into consideration as
possible psychological factors. Orthodontic treatment need was assessed using the
Index of Orthodontic Treatment Need-Dental Health Component (IOTN-DHC), the Index
of Orthodontic Treatment Need-Aesthetic Component (IOTN-AC) and the Dental
Aesthetic Index (DAI). Possible significant correlations between the collected
parameters and OHRQoL were evaluated by means of linear regression analysis.
RESULTS: Objective orthodontic treatment need (IOTN-DHC and DAI) was
significantly correlated with OHRQoL. Further factors significantly influencing
OHRQoL in children and adolescents were age, HRQOL, self-esteem and behavioural
problems. CONCLUSIONS: Objective orthodontic treatment need significantly
influences OHRQoL in children and adolescents. Further studies are required to
investigate if OHRQoL may be improved by correcting misaligned teeth and jaws.
PMID- 29947815
TI - Oculoauriculovertebral spectrum and maxillary sinus volumes : CT-based
comparative evaluation.
AB - OBJECTIVES: To evaluate, by comparing maxillary sinus volumes, how asymmetries
related to oculoauriculovertebral spectrum (OAVS) affect upper-jaw development.
METHODS: From pre-existing multislice spiral computed tomography (MSCT) datasets,
we selected 20 cases of 11 female and 9 male patients aged 6.1-24 years who were
clinically and radiographically symmetrical (group 1) plus 20 cases of 8 female
and 12 male patients aged 5.7-23.9 years who had OAVS (group 2). After three
dimensional reconstruction of the datasets, the volumes of the left and right
maxillary sinuses were calculated and compared based on patient groups and based
on the sides affected or unaffected by OAVS. To this end, the OAVS patients were
subdivided into a group in whom both external acoustic pores were
radiographically present (group 2a) and a group in whom the pore on the affected
side was congenitally missing (group 2b). RESULTS: Intrarater reliability was
very high (0.997). Significantly larger volumes of the maxillary sinuses,
amounting to a mean of 13.4 ml, were observed in the control group than in the
asymmetric OAVS groups where the volumes averaged 9.8 ml or 10.3 ml, respectively
(p = 0.03). No statistically significant differences in sinus volumes were found
between the two OAVS groups (p = 0.557) and between the sides affected or
unaffected by the OAVS (p = 0.8311 in group 2a and 0.4961 in group 2b).
CONCLUSIONS: Overall, we found the volumes of both maxillary sinuses to be
somewhat smaller in the asymmetric patients than in the symmetric control group.
This might indicate that OAVS was associated with a mild generalized hypoplasia
of the maxilla, but significantly different sinus volumes were not seen between
the affected and unaffected sides.
PMID- 29947816
TI - Structural chromosome rearrangements and polymorphisms identified in Chinese
wheat cultivars by high-resolution multiplex oligonucleotide FISH.
AB - KEY MESSAGE: High-resolution multiplex oligonucleotide FISH revealed the frequent
occurrence of structural chromosomal rearrangements and polymorphisms in widely
grown wheat cultivars and their founders. Over 2000 wheat cultivars including 19
founders were released and grown in China from 1949 to 2000. To understand the
impact of breeding selection on chromosome structural variations, high-resolution
karyotypes of Chinese Spring (CS) and 373 Chinese cultivars were developed and
compared by FISH (fluorescence in situ hybridization) using an oligonucleotide
multiplex probe based on repeat sequences. Among them, 148 (39.7%) accessions
carried 14 structural rearrangements including three single translocations
(designated as T), eight reciprocal translocations (RT), one pericentric
inversion (perInv), and two combined variations having both the deletion and
single translocations. Five rearrangements were traced to eight founders,
including perInv 6B detected in 57 cultivars originating from Funo, Abbondanza,
and Fan 6, T 1RS?1BL in 47 cultivars derived from the Lovrin series, RT 4AS?4AL
1DS/1DL?1DS-4AL in 31 varieties from Mazhamai and Bima 4, RT 1RS?7DL/7DS?1BL in
three cultivars was from Aimengniu, and RT 5BS?5BL-5DL/5DS?5DL-5BL was only
detected in Youzimai. In addition to structural rearrangements, 167 polymorphic
chromosome blocks (defined as unique signal patterns of oligonucleotide repeat
probes distributed within chromosomes) were identified, and 59 were present in
one or more founders. Some specific types were present at high frequencies
indicating selective blocks in Chinese wheat varieties. All cultivars and CS were
clustered into four groups and 15 subgroups at chromosome level. Common block
patterns occurred in the same subgroup. Origin, geographic distribution, probable
adaptation to specific environments, and potential use of these chromosomal
rearrangements and blocks are discussed.
PMID- 29947817
TI - [Comparison of two models of a treatment area with respect to treatment times in
critically ill patients : A pilot study].
AB - BACKGROUND: In the case of a mass casualty incident an advanced medical post
(AMP) plays a central role in the medical care by ambulance service and civil
protection units. Besides the traditional organization with one triage category
per medical services tent, it can also be structured in a mixed form (i.e. a
defined number of patients with different triage categories are assigned to each
medical services tent). To date it remains unclear which organization format is
better in order to rapidly evacuate those patients with the highest priority.
METHODS: The Medical Task Force of Lower Franconia treated 50 identical and
standardized training patients including 18 triage category red/emergency (36%),
12 triage category yellow/urgent (24%), 18 triage category green/non-urgent (36%)
and 2 triage category black/dead (4%) in the course of a scheduled field exercise
within two consecutive training sessions (first session: classical structure,
second session: mixed structure). The training patients were represented by a
dynamic patient simulation, whereby simulation cards showed injury patterns and
the external appearance of the patients at a defined point which required certain
interventions. The patients' conditions changed when these measures were
accomplished or neglected. The length of stay of the patients with the triage
category red/emergency at the AMP (start of triage to start evacuation) as well
as the overall number of evacuated patients were collated and compared. RESULTS:
Out of 18 patients with the triage category red/emergency, 13 patients in each
session were evacuated in one pass. During the first session the mean evacuation
time at the AMP was 25 min and during the second session the mean evacuation time
was 18 min. After the end of the 90 min of exercise time in the first session 14
non-critical patients (triage categories yellow/urgent and green/non-urgent, n =
30) were still left at the AMP (16 evacuated) and in the second session 12 (18
evacuated). CONCLUSION: Depending on the mission requirements the mixed form of
AMP organization can provide several advantages. In addition to rapid operational
readiness and high flexibility the patient distribution by triage category could
be processed better and the evacuation time of critical patients could be
shortened.
PMID- 29947818
TI - MRI-based high-precision irradiation in an orthotopic pancreatic tumor mouse
model : A treatment planning study.
AB - BACKGROUND AND PURPOSE: Recently, imaging and high-precision irradiation devices
for preclinical tumor models have been developed. Image-guided radiation therapy
(IGRT) including innovative treatment planning techniques comparable to patient
treatment can be achieved in a translational context. The study aims to evaluate
magnetic resonance imaging/computed tomography (MRI/CT)-based treatment planning
with different treatment techniques for high-precision radiation therapy (RT).
MATERIALS AND METHODS: In an orthotopic pancreatic cancer model, MRI/CT-based
radiation treatment planning was established. Three irradiation techniques
(rotational, 3D multifield, stereotactic) were performed with the SARRP system
(Small Animal Radiation Research Platform, Xstrahl Ltd., Camberley, UK). Dose
distributions in gross tumor volume (GTV) and organs at risk (OAR) were analyzed
for each treatment setting. RESULTS: MRI with high soft tissue contrast improved
imaging of GTV and OARs. Therefore MRI-based treatment planning enables precise
contouring of GTV and OARs, thus, providing a perfect basis for an improved dose
distribution and coverage of the GTV for all advanced radiation techniques.
CONCLUSION: An MRI/CT-based treatment planning for high-precision IGRT using
different techniques was established in an orthotopic pancreatic tumor model.
Advanced radiation techniques allow considering perfect coverage of GTV and
sparing of OARs in the preclinical setting and reflect clinical treatment plans
of pancreatic cancer patients.
PMID- 29947819
TI - How do patients and surgeons decide on uterine preservation or hysterectomy in
apical prolapse?
AB - Increasingly, uterine preservation surgeries are being performed for treating
apical prolapse. Several types of procedures and surgical approaches to correct
apical prolapse have been described in the literature. Despite this, there
remains inadequate information to provide evidence-based recommendations
regarding the optimal treatment approach and materials to use, and trials are
ongoing to identify the optimal techniques. In the future, our patients may be
the strongest determining influence when it comes to choice of apical prolapse
surgery, with factors such as autonomy, reproduction, intimacy and fear
influencing their decision. It is our opinion that the two most powerful forces
behind the choice of apical POP surgical technique are the woman's personal
desire for uterine preservation or not and the surgeon's personal choice of
procedure based on training received. Present management of apical prolapse
involves understanding patient goals and acknowledging their treatment
preferences and values.
PMID- 29947820
TI - [Placebo and nocebo effects on itch : Methodological and clinical implications].
AB - Patients often experience positive (placebo) or negative (nocebo) treatment
effects due to the positive or negative expectations they have about the
treatment. Placebo and nocebo effects have only relatively recently received
attention for itch. Experimental studies indicate that, in line with research in
other areas, such as pain, learning via verbal suggestion and conditioning plays
a key role in placebo and nocebo effects on itch. Results on contagious itch
emphasize the role of observational learning and suggest that itch sensations
might be particularly susceptible to suggestion and therefore placebo and nocebo
effects. Substantial itch reductions in the placebo arms of clinical trials
suggest that placebo effects are also important for clinical practice. In this
article, an overview is given of how placebo and nocebo effects on itch can
optimally be used in research and for the treatment of itch.
PMID- 29947822
TI - Rural-urban inequities in deaths and cancer mortality amid rapid economic and
environmental changes in China.
AB - OBJECTIVES: This paper examines rural-urban inequities in mortality and cancer
mortality amid rapid economic growth and environmental degradation in China.
METHODS: SPSS and Joinpoint Regression were used to analyze the 2002-2015
datasets from all death registries in China and associated economic and
environmental data. RESULTS: Death and cancer mortality rates among rural
residents were higher and increased faster than urban residents. In particular,
rural men 30-34 years old were 44% more likely to die from cancer and over 67%
more likely to die from all causes, compared to their urban counterparts. Among
rural women 15-19 years old, the death rate was 47% higher and the cancer
mortality rate was 44% higher than among urban women. Death and cancer mortality
rates tended to be positively associated with economic growth and air pollution
variables. CONCLUSIONS: Rural-urban health inequities have widened in China, with
rural youth at the greatest disadvantage. The anticipated health benefits from
income growth may have been offset by the impact of air pollution, which calls
for further investigation into the causes of rural-urban health inequities.
PMID- 29947821
TI - Health inequality and community-based health insurance: a case study of rural
Rwanda with repeated cross-sectional data.
AB - OBJECTIVES: To investigate the inequality in medical care utilization and
household catastrophic health spending (HCHS) between the poverty and non-poverty
residents in rural Rwanda and their links with community-based health insurance
(Mutuelles). METHODS: We used the 2005 and 2010 nationally representative
Integrated Living Conditions Surveys. We estimated multilevel logistic regression
models to obtain the adjusted levels and trends of both absolute and relative
inequalities and examined associations between Mutuelles status and these
inequalities. RESULTS: Significant inequality between the two income groups, in
both absolute and relative measures of medical care utilization and HCHS remained
unchanged in 2005 and 2010. Significant reduction in adjusted absolute inequality
in percentage of HCHS between the two years was not associated with Mutuelles
status. CONCLUSIONS: While Mutuelles promoted medical care utilization and
reduced HCHS, it did not play a significant role in reducing their inequalities
by poverty status between 2005 and 2010. Future studies should assess the impact
of additional strategies (e.g., the exemption of Mutuelles premiums and
copayments for households living in poverty), on reducing inequality by poverty
status.
PMID- 29947823
TI - Trajectories of health-related quality of life in immigrants and non-immigrants
in Germany: a population-based longitudinal study.
AB - OBJECTIVES: Due to a lack of longitudinal studies on health in immigrants, the
purpose of the present study is to investigate trajectories of health-related
quality of life (HRQoL) in immigrants and non-immigrants in Germany by
considering the impact of immigration-related factors. METHODS: Based on
longitudinal SOEP data from 2002 to 2012, the trajectories of the mental (MCS)
and physical component (PCS) of HRQoL (assessed with SF-12v2) were analyzed in
8546 subjects, including 1064 immigrants by conducting hierarchical linear
models. RESULTS: MCS remains stable over time, whereas PCS shows a decrease,
influenced by increasing age. There were no differences between immigrants and
non-immigrants concerning PCS trajectories as well as no influence of immigration
related factors on it. In contrast, MCS trajectories were influenced by
immigration-related factors: 2nd-generation immigrants, participants from Turkey
or Southern Europe and those who immigrated at young age show a slight decrease
in MCS over time. CONCLUSIONS: The results show negative association between MCS
and time in different groups of immigrants. Future research is needed for better
conceptualization of the complex interplay between health and migration over time
to identify subgroups at greater risk for mental distress.
PMID- 29947824
TI - Health challenges and perspectives for sub-Saharan Africa.
PMID- 29947825
TI - Correction to: The impact of low education and poor health on unemployment varies
by work life stage.
AB - During the calculation of the physical component score and the mental component
score, the score of the RAND 1 was erroneously coded in the opposite direction.
After correcting this mistake, the interaction between low education and poor
physical health on unemployment in early work life becomes statistically
significant.
PMID- 29947827
TI - Maternal employment and children's socio-emotional outcomes: an Australian
longitudinal study.
AB - OBJECTIVES: Among children, poor socio-emotional functioning leads to poor health
and well-being during childhood and later in life, and so understanding its
social determinants is important. This study's objective is to examine how
maternal employment influences children's socio-emotional outcomes in an
Australian sample of families with two biological parents, testing the mediating
role of maternal mental health, parenting practices, and parental income.
METHODS: We analyze six waves of panel data from the Longitudinal Study of
Australian Children (n = 7524 children, 29,701 observations) using random-effect
models. RESULTS: Children of employed mothers display better socio-emotional
outcomes than children of non-employed mothers, though the effect magnitude is
only moderate. Associations are stronger for internalizing than externalizing
problems, and not mediated by parental mental health, parenting practices, or
household income. CONCLUSIONS: Our findings can inform sociopolitical debates on
the social value of maternal labor force participation and its impacts on
children. They suggest that incentivizing maternal employment should bear no
detrimental consequences on their children's socio-emotional functioning. The
different associations found for children's internalizing and externalizing
problems stress the value of distinguishing these constructs.
PMID- 29947826
TI - How does the social environment during life course embody in and influence the
development of cancer?
AB - OBJECTIVES: This review assessed the complex longitudinal processes involved in
cancer etiology during life course to understand how the social inequality may be
embodied in and influence cancer risk. METHODS: A narrative literature review was
performed with a keyword search conducted using PubMed, Scientific Electronic
Library Online and Google. Three aspects of literatures were mainly included:
social environmental mechanisms of cancer, life course of cancer development and
social inequality of cancer risk. This review was complemented with manual
searches of relevant journals and reference lists of primary articles. RESULTS:
Social inequality is mostly embodied in genetic susceptibility and early
childhood development, the duration and intensity of exposures and the access to
medical resources, which influence the timing and accumulation of cancer risk
during life course. CONCLUSIONS: The individuals with lower socioeconomic status
are more likely to have higher cancer risk because of more frequency of timing
and quantity of accumulation of adverse exposures and greater impact on
epigenetic mechanisms. Primary prevention is the best prevention strategy to
reduce cancer risk.
PMID- 29947828
TI - Socio-economic status and chronic disease in the West Bank and the Gaza Strip: in
and outside refugee camps.
AB - OBJECTIVES: The study investigated the association between socio-economic status
(SES) and self-reported chronic disease (CD) among the Palestinian population in
the Occupied Palestinian Territory, and whether this association was similar in
the refugee camps. METHODS: We used data from representative samples in 2006 and
2010 collected by the Palestinian Central Bureau of Statistics. SES was defined
by education, wealth and employment status. Associations between SES and CD were
analysed and stratified by living in or outside refugee camps. RESULTS: CD
prevalence increased among men and decreased among women in all SES categories
and the Odds Ratio for CD was higher inside than outside the refugee camps,
except for women in 2006. In both 2006 and 2010 the odds ratio of CD was higher
among the lowest SES groups. The pattern of the negative association between SES
and CD was similar in and outside the refugee camps. CONCLUSIONS: We found that
the highest burden of CD is among those with low SES. In spite of a higher CD
Odds Ratio in the refugee camps, the pattern of association between SES and CD
did not differ in the refugee camps.
PMID- 29947829
TI - Childhood experiences of parenting and cancer risk at older ages: findings from
the English Longitudinal Study of Ageing (ELSA).
AB - OBJECTIVES: Despite the importance of childhood experiences for adult health and
psychosocial factors for cancer development, parenting, a key childhood
psychosocial exposure, has yet to be studied in relation to cancer risk at older
ages. We examined whether childhood experiences of poor-quality parenting are
associated with an increased risk of cancer at older ages. METHODS: We used a
sample of 4471 community dwellers aged >= 55 years in 2007. Poor-quality
parenting was defined as low levels of parental care and high levels of parental
overprotection. RESULTS: Overall poorer experiences of parenting, decreasing
parental care and increasing parental overprotection were associated with
increased risk of incident all-site and skin cancer in men, but not in women.
Increasing paternal overprotection was also associated with increased risk of
incident colorectal cancer in men. Overall poorer experiences of parenting and
increasing paternal overprotection were associated with increased risk of
prevalent all-site and colorectal cancer in women. Adjustment for covariates
explained a small part of these associations. CONCLUSIONS: Older adults who
reported childhood experiences of poorer quality parenting appear to have an
increased risk of cancer. These findings improve our understanding of the role of
psychosocial factors in cancer over the life course.
PMID- 29947830
TI - [Resuscitative endovascular balloon occlusion of the aorta : Bridge to surgery].
AB - BACKGROUND: Severe hemorrhage remains the leading cause of death among trauma
patients. Resuscitative balloon occlusion of the aorta (REBOA) is an endovascular
alternative to the established emergency room thoracotomy with cross-clamping of
the aorta in patients with severe abdominal or pelvic bleeding. OBJECTIVE: The
article reports on initial experiences with REBOA. METHODS: Based on the
literature and own experiences the pathophysiology, indications,
contraindications, technical details and first results with REBOA are presented.
RESULTS: The REBOA procedure is indicated in patients with treatment-refractive
hemorrhagic shock with severe abdominal or pelvic bleeding. Via a transfemoral
approach a balloon catheter is placed in the aorta and inflated. Depending on the
indication the aortic occlusion is located in a supradiaphragmatic (zone 1) or
infrarenal (zone 3) position. Experimental results proved a significant increase
in central perfusion pressure after performance of REBOA. Furthermore, first
clinical data indicate an improved patient survival rate after trauma.
Improvements of the devices and minimizing the access trauma using small 7 Fr
sheaths decreased the perioperative complication rate. CONCLUSION: The REBOA
procedure is a promising endovascular technique for temporary stabilization of
the circulation in patients with hemorrhagic shock. Further clinical studies and
registries have yet to prove its superiority over emergency room thoracotomy.
PMID- 29947831
TI - [Intramedullary versus extramedullary stabilization of distal extra-articular
tibial fractures : The UK FixDT trial (ISRCTN99771224)].
PMID- 29947832
TI - [Does a physician have to inform the patient about the rare risk of priapism
before administering an anticoagulant?]
AB - There are no pharmaceuticals without side effects. Primary care physicians and
especially hospital staff have to ask themselves every time they are
administering medication whether they should inform the patient about possible
risks and alternative treatment options. The "bizarre" side effects which can
occur even from taking routine medication are illustrated by a legal case decided
by the District Court of Hannover: After surgery a patient developed an
anticoagulant-induced priapism. The surgery itself was not subject of the court
case but the patient sued the hospital for neglecting to inform him about the
possible risk of priapism and about the alternative treatment with rivaroxaban,
which both parties agreed had not happened. The District Court now had to decide
whether the hospital is duty bound provide patients with such detailed
information in order to obtain informed consent. The Hannover Court, and also
later the Court of Appeal in Celle, answered this question in the negative;
however, the decision shows that it is not sufficient for the treating physician
to refer the patient to the patient information leaflet. Instead the physician is
legally bound to personally and orally inform the patient about the risks and
possible side effects, even when they are rare but typically associated with the
prescribed medication.
PMID- 29947833
TI - Myocardial reperfusion with tirofiban injection via aspiration catheter :
Efficacy and safety in STEMI patients with large thrombus burden.
AB - BACKGROUND: There is no consensus on the use of thrombus aspiration (TA) in
primary percutaneous coronary intervention (PPCI), and few studies have focused
on the performance of tirofiban via TA catheter after PPCI. Our study
investigated the clinical outcome of tirofiban injection through TA in acute ST
segment elevation myocardial infarction (STEMI) patients with large thrombus
burden undergoing PPCI treatment. PATIENTS AND METHODS: The study comprised 122
STEMI patients who underwent TA during PPCI. Participants were randomly divided
into two groups. Group A received intravenous tirofiban injection and tirofiban
injection via a TA catheter to the infarcted coronary artery after aspiration (n
= 61). Group B received intravenous tirofiban injection only (n = 61). Baseline
clinical information and follow-up data were collected for both groups. Coronary
angiography, electrocardiography, and echocardiography findings as well as major
adverse cardiovascular events (MACE) were recorded. RESULTS: There were
significant differences in postprocedural Thrombolysis in Myocardial Infarction
(TIMI) grade 2 and 3 flow between the two groups (p = 0.021, p = 0.006,
respectively). The incidence of slow-flow in group A was significantly lower than
that of group B (p = 0.011). An increased incidence of no ST-segment resolution
was observed in group B (p = 0.011). There were fewer major adverse
cardiovascular events in group A than in group B, but the difference was not
statistically significant. CONCLUSION: Selective tirofiban injection via TA
catheter during PPCI may improve myocardial reperfusion in STEMI patients with
large thrombus burden.
PMID- 29947834
TI - Treatment options in myocarditis and inflammatory cardiomyopathy : Focus on i. v.
immunoglobulins.
AB - For myocarditis and inflammatory cardiomyopathy, an etiologically driven
treatment is today the best option beyond heart failure therapy. Prerequisites
for this are noninvasive and invasive biomarkers including endomyocardial biopsy
and polymerase chain reaction on cardiotropic agents. Imaging by Doppler
echocardiography and cardiac magnetic resonance imaging as well as cardiac
biomarkers such as C-reactive protein, N-terminal pro-B-type natriuretic peptide
, and troponins can contribute to the clinical work-up of the syndrome but not
toward elucidating the underlying cause or pathogenetic process. This review
summarizes the phases and clinical features of myocarditis and gives an up-to
date short overview of the current treatment options starting with heart failure
and antiarrhythmic therapy. Although inflammation in myocardial disease can
resolve spontaneously, often specific treatment directed against the causative
agent is required. For fulminant, acute, and chronic autoreactive myocarditis,
immunosuppressive treatment has proven to be beneficial in the TIMIC and ESETCID
trials; for viral cardiomyopathy and myocarditis, intravenous immunoglobulin IgG
subtype and polyvalent intravenous immunoglobulins IgG, IgA, and IgM can
frequently resolve inflammation. However, despite the elimination of
inflammation, the eradication of parvovirus B19 and human herpesvirus-6 is still
a challenge, for which ivIg treatment can become a future key player.
PMID- 29947835
TI - Lipopeptide biodiversity in antifungal Bacillus strains isolated from Algeria.
AB - Several Bacillus strains have been well studied for their ability to control soil
borne plant diseases. This property is linked to the production of several
families of lipopeptides. Depending of their structure, these compounds show
antifungal and/or plant systemic resistance inducing activities. In this work,
the biodiversity of lipopeptides produced by different antifungal Bacillus
strains isolated from seeds, rhizospheric, and non-rhizospheric soils in Algeria
was analyzed. Sixteen active strains were characterized by PCR for their content
in genes involved in lipopeptide biosynthesis and by MALDI-ToF for their
lipopeptide production, revealing a high biodiversity of products. The difficulty
to detect kurstakin genes led us to design two new sets of specific primers. An
interesting potential of antifungal activity and the synthesis of two forms of
fengycins differing in the eighth amino acid (Gln/Glu) were found from the strain
8. Investigation of its genome led to the finding of an adenylation domain of the
fengycin synthetase predicted to activate the glutamate residue instead of the
glutamine one. According to the comparison of both the results of MALDI-ToF-MS
and genome analysis, it was concluded that this adenylation domain could activate
both residues at the same time. This study highlighted that the richness of the
Algerian ecosystems in Bacillus strains is able to produce: surfactin,
pumilacidin, lichenysin, kurstakin, and different types of fengycins.
PMID- 29947836
TI - Influences of light on growth, reproduction and hypocrellin production by Shiraia
sp. SUPER-H168.
AB - Light is a very important signal for fungi since it influences many different
physiological responses. The effects of dark or light at different wavelengths on
growth, reproduction and hypocrellins of Shiraia sp. SUPER-H168 were studied:
dark, white, red, yellow, green, blue and purple. All incubations under different
light conditions had significant stimulating effects on aerial hyphae and
suppressing effects on hypocrellin biosynthesis compared with dark incubation.
Under blue and purple light especially blue light, the colonies with profuse
growth of aerial mycelium were formed. Hypocrellin production reached 13.73 mg
per dish under dark condition, and decreased to 4.01 mg and 2.83 mg per dish
under white and blue light, respectively. Light condition not only influenced
hypocrellin production but also influenced the composition of hypocrellins. Four
types of hyphae, namely surface, aerial, biofilm and penetrative hyphae, were
observed by light microscopy and SEM. This study found that biofilm hyphae was so
closely connected with production of secondary metabolites, and hypocrellins were
only produced by biofilm hyphae. Light promoted sexual development and inhibited
asexual reproduction, especially blue light strongly inhibited asexual
development.
PMID- 29947837
TI - Microbially-enriched poultry litter-derived biochar for the treatment of acid
mine drainage.
AB - Sulfate-reducing bacteria (SRB) and a biochar array were used to reduce sulfate
concentrations and the levels of metals in acid mine drainage (AMD) waters. Cow
manure SRB-enriched biochar promoted sulfate reductions of 41% compared to
original AMD, and 39% compared to other treatments (control, AMD sediment,
sludge). Treatments reduced levels of all analyzed metals below Brazilian
official standards. DGGE showed a significant relation between SRB-source and SRB
structural community, where cow manure and sludge presented the more cohesive
community structure throughout the monitoring (180 days). The study showed that
AMD treatment alternatives can be applied and are effective in reducing the
contamination of wastewaters.
PMID- 29947838
TI - Functional characterization of ligninolytic Klebsiella spp. strains associated
with soil and freshwater.
AB - Overcoming recalcitrance of lignin has motivated bioprospecting of high-yielding
enzymes from environmental ligninolytic microorganisms associated with
lignocellulose degrading-systems. Here, we performed isolation of 21 ligninolytic
strains belonging to the genus Klebsiella spp., driven by the presence of lignin
in the media. The fastest-growing strains (FP10-5.23, FP10-5.22 and P3TM1)
reached the stationary phase in approximately 24 h, in the media containing
lignin as the main carbon source. The strains showed biochemical evidence of
ligninolytic potential in liquid- and solid media-converting dyes, which the
molecular structures are similar to lignin fragments. In liquid medium, higher
levels of dye decolorization was observed for P3TM.1 in the presence of methylene
blue, reaching 98% decolorization in 48 h. The highest index values (1.25) were
found for isolates P3TM.1 and FP10-5.23, in the presence of toluidine blue. The
genomic analysis revealed the presence of more than 20 genes associated with
known prokaryotic lignin-degrading systems. Identification of peroxidases (lignin
peroxidase-LiP, dye-decolorizing peroxidase-DyP, manganese peroxidase-MnP) and
auxiliary activities (AA2, AA3, AA6 and AA10 families) among the genetic
repertoire suggest the ability to produce extracellular enzymes able to attack
phenolic and non-phenolic lignin structures. Our results suggest that the
Klebsiella spp. associated with fresh water and soil may play important role in
the cycling of recalcitrant molecules in the Caatinga (desert-like Brazilian
biome), and represent a potential source of lignin-degrading enzymes with
biotechnological applications.
PMID- 29947840
TI - Hybrid high tibial osteotomy is superior to medial opening high tibial osteotomy
for the treatment of varus knee with patellofemoral osteoarthritis.
AB - PURPOSE: To evaluate patellofemoral congruity after opening wedge high tibial
osteotomy (OWHTO) and hybrid HTO. METHODS: Twenty-four knees with hybrid HTO and
24 with OWHTO were evaluated in this study. The Caton-Deschamps and modified
Miura-Kawamura indices were used to evaluate pre- and post-operative patellar
heights for both types of surgery. Tibial tuberosity-trochlear groove (TT-TG)
distance, patellar tilt, and medial and lateral joint space at the patellofemoral
joint were compared. Anterior knee pain was assessed using the Kujala anterior
knee pain scale. RESULTS: There was no significant difference between the
correction angles of the hybrid HTO and OWHTO. Pre- and post-operative values for
the Caton-Deschamps and modified Miura-Kawamura indices in patients who underwent
hybrid HTO changed from 0.90 to 0.94 and from 0.95 to 1.03, respectively, with no
significant differences noted. Following OWHTO, these values decreased
significantly from 0.91 to 0.73 and from 1.06 to 0.84, respectively (p < 0.01).
The post-operative patellar height after OWHTO was significantly lower than that
after hybrid HTO (p < 0.01). After hybrid HTO, the TT-TG distance decreased
significantly from 11.4 to 7.4 (p < 0.01), but it did not change significantly
after OWHTO. Although pre- and post-operative patellar tilt were not altered
significantly in either group, the medial joint space of the patellofemoral joint
was significantly increased post-operatively following hybrid HTO (p = 0.035).
The pre-operative Kujala scores were significantly lower in the hybrid HTO group,
but post-operative scores improved in both groups. CONCLUSIONS: Hybrid HTO
provides a better post-operative patellofemoral joint than does OWHTO with regard
to patellar position and reduction of the TT-TG distance, as well as improved
clinical outcomes. Hybrid HTO, rather than OWHTO, is the preferred technique for
the treatment of varus knees combined with patellofemoral osteoarthritis. LEVEL
OF EVIDENCE: Retrospective comparative study, Level III.
PMID- 29947839
TI - Bicruciate lesion biomechanics, Part 1-Diagnosis: translations over 15 mm at 90
degrees of knee flexion are indicative of a complete tear.
AB - PURPOSE: Understanding the pathomechanics of a bicruciate injury (BI) is critical
for its correct diagnosis and treatment. The purpose of this biomechanical study
aims to quantify the effects of sequential sectioning of the anterior cruciate
ligament (ACL) and posterior cruciate ligament (PCL) bundles on knee laxity.
METHODS: Twelve cadaveric knees (six matched pairs) were used. Knee laxity
measurements consisted of neutral tibial position, anterior-posterior
translation, internal-external rotation, and varus-valgus angulation in different
conditions: intact, ACL cut, incomplete BI (divided into two groups:
anterolateral (AL) bundle intact or posteromedial (PM) bundle intact) and
complete bicruciate tear. Data were collected using a Microscribe system at 0
degrees , 30 degrees , 60 degrees , and 90 degrees of knee flexion. RESULTS: In
comparison to the intact knees, incomplete BI and complete BI showed a
significant increase of total antero-posterior tibial translation. The largest
significant increase was observed at 90 degrees of flexion after a complete
bicruciate resection (p < 0.001). A threshold difference greater than 15 mm from
the intact could be used to identify a complete BI from an incomplete BI
evaluating the total antero-posterior translation at 90 degrees . All sectioned
states had significant increases compared with the intact condition in internal
external rotation and varus-valgus stability at all tested flexion angles.
CONCLUSION: Both incomplete and complete BI led to an important AP translation
instability at all angles; however, full extension was the most stable position
at all injured models. Total antero-posterior translation at 90 degrees of knee
flexion over 15 mm, in comparison to the intact condition, was indicative of a
complete BI. Since the appropriate assessment of a combined ACL and PCL lesion
remains a challenge, this study intends to assist its diagnosis. As BI's main
antero-posterior instability occurred at 90 degrees , a total antero-posterior
drawer test is proposed to evaluate BI in the clinical setting. Total antero
posterior translation at 90 degrees > 15 mm, in comparison to the intact
condition or the contra-lateral non-injured knee, can be used to identify a
complete from an incomplete BI.
PMID- 29947841
TI - Risk factors for residual pivot shift after anterior cruciate ligament
reconstruction: data from the MAKS group.
AB - PURPOSE: To investigate the risk factors for residual pivot shift test after
anterior cruciate ligament (ACL) reconstruction based on a multicenter
prospective cohort study. METHODS: This study included patients who were
registered in the Multicenter Arthroscopic Knee Surgery Study, a prospective
longitudinal multicenter cohort study, and who underwent primary ACL
reconstruction using autologous hamstring tendon graft between 2013 and 2016. The
exclusion criteria included prior injuries or surgeries in the contralateral
knee, prior ligamentous injuries in the involved knee, grade 2 or 3 concomitant
ligament injuries, and inflammatory or other forms of osteoarthritis. Data from
the preoperative period and at 1-year follow-up were used for further analysis,
and patients with incomplete data, re-injury and loss to follow-up were also
excluded. Logistic regression analysis was conducted with age, gender, Lachman
test, pivot shift test, KT measurement, hyperextension, single-bundle vs. double
bundle, meniscus injury sites, and meniscus treatments as the independent
variables, and postoperative pivot shift test was used as the dependent variable.
RESULTS: Three hundred and sixty-eight patients were included in the study.
Hyperextension knee (P = 0.025) and a preoperative pivot shift test under
anesthesia (P = 0.040) were identified as risk factors for a postoperative pivot
shift via logistic regression analysis. There were no statistically significant
differences in the other variables. CONCLUSIONS: The results from a multicenter
cohort study indicated that knee hyperextension and greater preoperative pivot
shift under anesthesia were risk factors for residual pivot shift at 1 year after
ACL reconstruction. In cases with a preoperative high-grade pivot shift and knee
hyperextension, additional anterolateral structure augmentation might be
considered in order to eliminate pivot shift and eventually obtain better
outcomes after ACL reconstruction. LEVEL OF EVIDENCE: II.
PMID- 29947842
TI - A polygon-shaped complex appearance of medial patellofemoral ligament with
dynamic functional insertion based on an outside-in and inside-out dissection
technique.
AB - PURPOSE: To describe the unclarified characteristics of medial patellofemoral
ligament and its relation to neighboring structures. METHODS: Sixteen fresh
frozen human knees were dissected in using outside-in and inside-out combined
technique. The patellar side attachment was observed from the inside view and
femoral side from outside view. RESULTS: The medial patellofemoral ligament was
described a complex and multiconnected structure. The femoral side included the
upper and lower portion, of which the upper portion attached on the femur with
mean width 7.5 +/- 1.1 mm and its superficial fibers extended to the adductor
magnus tendon and the medial gastrocnemius tendon, and of which the lower portion
appeared a right-triangle connected to the MCL without bony attachment. From
inside view, the patellar attachment consisted of the bony and non-bony parts.
The width of bony attachment was measured mean 16.3 +/- 3.8 mm, and the non-bony
attachment was found attached on the vastus intermedius tendon with mean width
21.7 +/- 4.8 mm. The average thickness was 0.4 +/- 0.1 mm and the length were
inside assessed mean 67.9 +/- 6.1 mm. CONCLUSION: The medial patellofemoral
ligament which dissected a complicated structure with bony and non-bony
attachment and multi-connected to neighboring structures on both patella and
femur side appears as a polygon-shaped complex structure.
PMID- 29947843
TI - A combined procedure with Bereiter-type trochleoplasty leads to a stable
patellofemoral joint at 5-year follow-up.
AB - PURPOSE: Trochlear dysplasia is a major risk factor predisposing to patellar
instability and has been reported to occur in up to 85% of patients with
recurrent patellar dislocation. Different operative techniques have been
described to correct trochlear dysplasia, including the Bereiter technique, in
which subchondral bone is removed and the cartilage can be compressed into a U
shaped groove. The hypothesis was that after a Bereiter-type trochleoplasty
combined with medialisation of the tibial tubercle and MPFL reconstruction,
patellar pain and instability decreased and anatomic reconstruction can be seen
radiographically after 5-year follow-up. METHODS: Between 2004 and 2011, a
combined procedure including Bereiter-type trochleoplasty was performed on 21
consecutively included patients (22 knees) with objective patellar instability
and severe trochlear dysplasia. Instability and pain were assessed preoperatively
and 3, 6, 12, 24 and 60 months postoperatively with the visual analogue scale
(VAS) for pain and instability, Kujala, International Knee Documentation
Committee Subjective Knee Evaluation (IKDC SKE) and Short Form Health Survey (SF
36). Pre- and postoperatively, a true lateral radiograph was made to investigate
the presence of the crossing sign and to measure the trochlear bump and trochlear
depth, as well as a sunrise patella view to measure the sulcus angle. RESULTS:
VAS pain and instability, Kujala and IKDC SKE improved significantly 5 years
after trochleoplasty (p < 0.05). SF-36 showed no significant improvement. None of
the patients reported patellar dislocations postoperatively. Sport activities
remained limited. Postoperative radiographs showed no crossing sign. There was a
significant increase in trochlear depth (p < 0.0001) and also a significant
decrease in trochlear bump and sulcus angle (both p < 0.0001). CONCLUSIONS: A
combined procedure consisting of Bereiter-type trochleoplasty, medialisation of
the tibial tubercle and MPFL reconstruction in patients with objective patellar
instability and severe trochlear dysplasia resulted in a clear decrease of pain
and instability. Radiological assessment showed anatomical reconstruction.
Nevertheless, residual symptoms remain and the possibility of future cartilage
damage is uncertain. LEVEL OF EVIDENCE: IV.
PMID- 29947844
TI - Increased fatigue of the biceps after tenotomy of the long head of biceps tendon.
AB - PURPOSE: The aim of this study is to evaluate the biomechanical parameters of
biceps fatigue (time to claudication during elbow flexion) and strength between
the shoulder where the tenotomy has been performed and the healthy arm. The
hypothesis of this study was that measuring biceps fatigue may be more useful for
determining functionality after tenotomy. METHODS: 52 patients from 2 hospitals
were selected to undergo biomechanical tests of healthy and pathological arms,
before and 12 months after surgery. The test consisted of (1) isometric
measurement of maximal voluntary contraction (MVC) in elbow flexion and forearm
supination (MVS) at baseline conditions. (2) Biceps fatigue test was performed by
a submaximal contraction to 33% of MVC maintained at a time as well recorded to
the time to claudication. (3) After claudication, measurements of the MVC and MVS
were recorded. In addition, the Constant score, SSI functional scale, VAS scale
and perceived symptoms were evaluated. RESULTS: Of the 52 patients included in
the study, 26 met the selection criteria. Two patients were lost to follow-up.
The mean age was 55 +/- 5.6 years. Popeye sign was observed in 58.3% of the
cases. Two patients were not satisfied with the results. Preoperatively, MVC was
193.6 +/- 55.2 N, which significantly improved after tenotomy to 252.1 +/- 61.2
N, but this value was less than the healthy arms (280 +/- 68 N). The fatigue time
decreased from 141.9 +/- 69.7 s preoperatively to 94.2 +/- 29.9 s after tenotomy.
There was also an improvement in the strength of the arm after the fatigue test.
No differences in supination force were found. The Constant, SSI and VAS rating
scales improved significantly. CONCLUSIONS: Despite functional improvements of
the long head of biceps tendon (LHBT) after tenotomy, this study demonstrates
that the shoulder where the tenotomy has been performed will fatigue more quickly
than it did preoperatively. Despite this, an improvement in the isometric
contraction in flexion of the elbow with respect to the preoperative values.
However, this improvement did not reach the flexion power of the contralateral
healthy arm. No changes were observed in the supination force of the forearm.
LEVEL OF EVIDENCE: III.
PMID- 29947845
TI - All-arthroscopic release for treating severe knee extension contractures could
improve the knee range of motion and the mid-term functional outcomes.
AB - PURPOSE: To evaluate the safety, feasibility, and effectiveness of an all
arthroscopic technique for the intra- and extraarticular release of severe knee
extension contractures. METHODS: From 2012 to 2016, 25 patients with severe knee
extension contractures (less than 45 degrees range of flexion) were treated with
an all-arthroscopic release technique. The patients underwent intra- and
extraarticular arthroscopic release and arthroscopic-assisted mini-incision
quadriceps plasty. The post-operative rehabilitation was initiated the first day
after the procedures. Comprehensive clinical follow-up evaluations including the
range-of-motion (ROM) assessment, the Lysholm score, and the International Knee
Documentation Committee (IKDC) score were performed on all patients. RESULTS: The
median follow-up time was 28 months (range 12-65 months). The ROM improved from
23.9 degrees +/- 7.5 degrees pre-operatively to 105.9 degrees +/- 6.5 degrees
at the final follow-up (P < 0.001). In addition, the Lysholm score increased from
59.9 +/- 5.2 pre-operatively to 89.7 +/- 3.3 (P < 0.001). The IKDC score
increased from 47.6 +/- 3.4 pre-operatively to 91.7 +/- 2.4 (P < 0.001). All
patients were satisfied with their final ROM and functional outcomes. CONCLUSION:
The all-arthroscopic release technique was a safe, feasible and effective method
for treating severe knee extension contractures. The severe knee extension
contractures may be successfully addressed by the all-arthroscopic release
technique during our clinical practice. LEVEL OF EVIDENCE: IV.
PMID- 29947846
TI - The native coronal orientation of tibial plateaus may limit the indications to
perform a kinematic aligned total knee arthroplasty.
AB - PURPOSE: To investigate the coronal alignment of tibial plateaus in normal and
osteoarthritic knees and to simulate the effects of a tibial cut performed in
total knee arthroplasty (TKA) using a kinematic alignment technique with standard
instrumentation. METHODS: The coronal alignment of tibial plateaus was measured
in three groups including group 1 (reference group), 50 cadaveric tibiae showing
no evidence of degenerative changes of tibial plateaus; group 2, 49 patients who
underwent MR of the knee, showing no or mild degenerative changes of the knee
joint and, group 3, 54 patients with knee osteoarthritis who underwent computer
assisted total knee arthroplasty. RESULTS: The coronal alignment of tibial
plateaus averaged 2.4 degrees with no significant differences between groups.
The mean coronal orientation of tibial plateaus was 3 degrees +/- 2 degrees in
men and 1.6 degrees +/- 2 degrees in women (p = 0.03). A coronal alignment of
tibial plateaus of 3 degrees or more was found in 69 cases (45%) and 5 degrees
or more in 23 (14.7%). The simulation of a tibial cut performed with an error of
3 degrees in varus in 15% of the subjects showing a native coronal orientation
of tibial plateaus of 3 degrees or more, led to a final tibial cut greater 6
degrees in 13.7% of cases. CONCLUSIONS: A coronal alignment of tibial plateaus
of 3 degrees or more in varus was found in near half of normal subjects and
osteoarthritic patients. A preoperative measurement of the coronal alignment of
tibial plateaus is advisable in any patients scheduled for kinematic aligned TKA.
As errors in the alignment of the tibial component of 3 degrees or more may
occur using standard instrumentations, the results of this study raise questions
on performing a kinematic aligned TKA with standard instrumentations. LEVEL OF
EVIDENCE: IV.
PMID- 29947847
TI - "Second-look" laparotomy: warranted, or contributor to excessive open abdomens?
AB - INTRODUCTION: The overuse of temporary abdominal closure and second look (SL)
laparotomy in emergency general surgery (EGS) cases has been questioned in the
recent literature. In an effort to hopefully decrease the number of open abdomen
(OA) patients, we hypothesize that reviewing our cases, many of these SL patients
could be managed with single-stage operative therapy and thus decrease the number
of OA patients. METHODS: This is a retrospective review of prospectively
collected data from Jun 2013-Jun 2014, evaluating EGS patients managed with an OA
who required bowel resection in either index or SL laparotomy. Demographics,
clinical variables, complications and mortality were collected. Fisher's exact t
test was used for statistical analysis. RESULTS: During this time frame, 96
patients were managed with OA and 59 patients required a bowel resection. 55
(57%) of those required one bowel resection at the index operation with 4 (4.2%)
only requiring one bowel resection at the second operation. In the patients
requiring bowel resections, 18 (30%) required a resection at SL. At SL
laparotomy, resection was required for questionably viable bowel at the index
operation 60% (11), whereas 39% (7) had normal appearing bowel. Indications for
resection at SL laparotomy included evolution of existing ischemia, new onset
ischemia, staple line revision, and "other". 23 patients (39%) were
hemodynamically unstable, contributing to the need for temporary abdominal
closure. In the multivariate analysis, preoperative shock was the only predictor
of need for further resection. Complications and mortality were similar in both
groups. CONCLUSION: Almost one-fifth of the patients undergoing SL laparotomy for
open abdomen required bowel resections, with 6.8% of those having normal
appearing bowel at index operation, therefore in select EGS patients, SL
laparotomy is a reasonable strategy.
PMID- 29947848
TI - Validation study of 3D-printed anatomical models using 2 PLA printers for
preoperative planning in trauma surgery, a human cadaver study.
AB - INTRODUCTION: 3D printing contributes to a better understanding of the surgical
approach, reduction and fixation of complex fractures. It is unclear how a 3D
printed model relates to a human bone. The accuracy of 3D-printed models is
important to pre-bend plates and fit of surgical guides. We conduct a validation
study in which we compare human cadavers with 3D-printed models to test the
accuracy of 3D printing. METHODS: Nine specimens were scanned, volume rendered
into 3D reconstructions and saved as STL data. All models were in a ratio of 1:1
printed on the Ultimaker 3 and Makerbot Replicator Z18. Two independent observers
measured all distances between the K-wires on the human cadavers, 2DCT, 3D
reconstruction, Meshlab and both printers. A paired Samples T test was used to
compare the measurements between the different modalities. RESULTS: The least
decrease in average distance in millimetres was seen in "the 3D printed pelvis
1", - 0.3 and - 0.8% on respectively the Ultimaker and Makerbot when compared
with cadaver Pelvis (1) The 3D model of "Hand 2" showed the most decrease, - 2.5
and - 3.2% on the Ultimaker and Makerbot when compared with cadaver hand (2) Most
significant differences in measurements were found in the conversion from 3D file
into a 3D print and between the cadaver and 3D-printed model from the Makerbot.
CONCLUSION: Our 3D printing process results in accurate models suitable for
preoperative workup. The Ultimaker 3 is slightly more accurate than the Makerbot
Replicator Z18. We advise that medical professionals should perform a study that
tests the accuracy of their 3D printing process before using the 3D-printed
models in medical practice.
PMID- 29947849
TI - Outcome of pubic rami fractures with or without concomitant involvement of the
posterior ring in elderly patients.
AB - INTRODUCTION: Pubic rami fractures are common fractures in a growing osteoporotic
geriatric population. Concomitant posterior ring fractures (cPRF) are often found
when properly looked for. The pain and consequent immobilization leaves this
vulnerable patient group at risk for complications. Conservative therapy is
usually sufficient, but with cPRF's surgery can be indicated. Although previous
studies have pointed out that mortality rates are high, longer term morbidity
outcomes are lacking. This study aims to further establish the longer term
consequences of these fractures. Risk factors will be identified for
complications, also addressing the possible differences between patients with or
without a cPRF. METHOD: Retrospective analysis of patients aged over 65 years
sustaining a pubic rami fracture in the North-West Hospital Group Alkmaar
combined with a survey to establish risk factors for morbidity and mortality
after 6 months' post trauma. Multiple logistic regression analysis was used to
identify risk factors. RESULTS: 117 patients matched inclusion criteria with a
median age of 83 and of which 86% was female. 23 cPRF's were identified.
Significant deterioration in ambulation and independency was found. 34% was
institutionalized at discharge. 49% lost their independent mobility status and
40% of the patients did not experience a full recovery. One-year mortality rate
was 23%. Patients with a cPRF had a significant higher complication rate (44 vs
18% p = 0.02), but mortality and other morbidity outcomes did not statistically
differ. The strongest predictor for 1-year mortality was complications during
admission and a dependent ambulatory status (OR 5.2 and 4.1 respectively).
CONCLUSION: Pubic fractures with or without involvement of the posterior pelvic
ring in patients aged over 65 have a significant impact on mobility and
independency. Mortality rates are similar to hip fracture patients. Careful
evaluation of every patient's mobility status is necessary to identify patients
at risk for complications and determine their future health care needs. Future
studies are needed to achieve consensus on diagnostic and treatment protocols and
identify ways to decrease the significant impact of this injury.
PMID- 29947850
TI - [Corticoids in patients with septic shock : Adjunctive glucocorticoid therapy in
patients with septic shock (ADRENAL) trial and Hydrocortisone plus
fludrocortisone for adults with septic shock (APROCCHSS)].
PMID- 29947851
TI - [In search of a cultural-technological history of genital prosthetics].
AB - Within the field of the history of technology, much has been written about the so
called "prosthesis boom" of the First World War. Most of these studies claim that
the main motive of the mass supply of artificial limbs to amputee soldiers was
primarily aimed at restoring the work force. However, because these studies often
lack a gender perspective, it stays unmentioned to what extent this also served
to reconstruct a hegemonic masculinity that had become fragile, if not destroyed
by the consequences of the war. Especially genital injuries-prevalent during
World War I and II as well as today-and their treatment and rehabilitation were
(and still are) often largely taboo. Because of this silence, there have been no
comprehensive studies or artifact collections on the cultural and technical
history of male genital prosthetics. By presenting different examples of
potential artifacts for such a history, the article suggests an object-based
approach to fill this academic void. These thoughts are based on the assumption
of a "doing gender through technology", hence that gender and sex are constantly
constructed and modeled through (medical) technological practices.
PMID- 29947852
TI - [Nephrology for urologists].
AB - By the very nature of things there are many overlaps between urology and
nephrology. A close cooperation between the two disciplines is necessary for the
benefit of the patient. From a nephrological perspective this article explains
when and why participation of a nephrologist in treatment is recommended. In this
context three essential points are explained: with respect to early recognition,
renal hematuria, microalbuminuria, proteinuria, limited renal filtration function
and glomerular filtration rate (GFR) are signs of renal disease; however, even
patients with renal cysts should consult a nephrologist as early as possible due
to the currently available treatment options. A delay in progression is possible
and necessary for all chronic kidney diseases, independent of the trigger. Even
when changes in the life style of the patient is troublesome and the adjustment
of hypertension and hyperlipidemia sounds banal, their consistent implementation
can result in a marked delay in the necessity for dialysis. The treatment of
renal comorbidities is decisive and depends on the severity of the kidney
disease. This includes the treatment of renal anemia, arterial hypertension,
metabolic acidosis, uremic complications, electrolyte and water balance
dysregulation and secondary hyperparathyroidism. By treating these comorbidities
a marked reduction in the increased cardiovascular risk of nephrology patients
can be achieved.
PMID- 29947853
TI - [Breastfeeding and potential sensory imprinting].
AB - Breastmilk provides well-known nutritional and functional advantages and in
addition a greater sensory variety as compared to infant formula. Volatile and
soluble sensory components from the mother's diet are transmitted prenatally into
the amniotic fluid and postnatally into breastmilk and can be detected by the
fetus and infant. Breastfeeding is suggested to serve as a bridge from prenatal
flavor experiences to the varied sensory world of complementary feeding and
family diet afterwards. Nevertheless definite data to prove this plausible
assumption are still missing. Randomized intervention trials with a necessary
long-term follow-up are difficult to implement and rarely achieved. Lasting
effects of early sensory experiences have so far been demonstrated mostly in the
first year of life and by applying intensive sensory interventions, which are
hardly possible in a habitual maternal diet. The practical relevance of a
potential sensory imprinting by breastfeeding still remains open. Nevertheless a
varied diet in pregnancy and lactation can be recommended not only for
nutritional reasons but also from a hedonic sensory perspective.
PMID- 29947854
TI - [The International Code of Marketing of Breastmilk Substitutes : History,
Content, and Significance].
AB - Breastfeeding is the physiological form of infant feeding and has many well
documented benefits. Low breastfeeding rates and short lactation periods have
significant negative ecological, economic, and social impact. The promotion of
breastfeeding supports the health of children and mothers and reduces costs to
the health system. However, the promotion of breastfeeding is regularly
undermined by inappropriate advertising of breast milk substitutes. To counteract
this, the International Code of Marketing of Breastmilk Substitutes was adopted
by the World Health Assembly (WHA) in 1981. Although the International Code of
Marketing of Breastmilk Substitutes and its subsequent resolutions have been
fully or partially incorporated into national law in 135 countries, the
provisions of the Code are continually violated. These violations are almost
always not punished at all or only insufficiently. For the promotion and
protection of breastfeeding, it is essential that health workers are familiar
with the Code and subsequent resolutions.This article presents and explains the
history, content, and importance of the International Code of Marketing of
Breastmilk Substitutes and gives an assessment of its implementation in practice.
PMID- 29947855
TI - [Is routine histopathologic examination of middle ear cholesteatoma necessary?]
AB - BACKGROUND: In the course of restoration of the middle ear, routine histological
examinations are initiated in many cases, although a middle ear cholesteatoma can
be clinically diagnosed in a normal case. AIM OF THE STUDY: To determine the
correlation between the surgeons' diagnosis and that of the pathologist and
comparison with literature data. To check the rate of unexpected diagnoses.
Analysis of the costs and survey of German ENT clinics with regard to handling of
the histological examination in suspected cholesteatoma. MATERIALS AND METHODS:
Retrospective evaluation of cholesteatoma cases of the ENT Department of the
University Medical Center of Mainz from 2010-2015. Germany-wide postal survey of
ENT clinics. RESULTS: In all, 449 operations for the rehabilitation of a middle
ear cholesteatoma, of which there were 312 (69.5%) first diagnoses and 137
(30.5%) recurrences. A histological examination was conducted in 78.6%. For first
diagnoses, the sensitivity of the clinical assessment was 97.9%, specificity 10%,
positive predictive value 96.3%, and negative predictive value 16.7%. Recurrences
showed values of 100%, 40%, 97.1% and 100%. Unexpected malignant findings did not
occur. This routine histological examination was performed by 58.6% of German ENT
hospitals. A total of 80% of those questioned this to be useful. A histological
examination cost an average of 14.06 ?. CONCLUSION: Intraoperatively, there is a
high degree of accuracy in diagnosing cholesteatoma. The cost factor of the
histological examination is low and should not be the basis for the decision. The
ear microscopy and the experience of the ear surgeon should be decisive for the
decision for histological examination.
PMID- 29947856
TI - [Influence of hearing on vestibulospinal control in healthy subjects. German
version].
AB - BACKGROUND: Balance control is based on multisensory interaction. In addition to
vestibular, proprioceptive and visual information, it seems that auditory input
also plays an important role. OBJECTIVES: The aim of the study was to investigate
the effect of hearing on vestibulospinal coordination and to obtain deeper
knowledge about mechanisms of audiovestibular interaction. MATERIALS AND METHODS:
In normal hearing, healthy subjects who performed the Unterberger (Fukuda)
stepping test with and without frontal presentation of noise, the distance of
displacement, the angle of displacement and the angle of rotation were measured
by means of ultrasound based cranio-corpo-graphy (CCG). Additionally, subjective
estimation of the effect of auditory input was compared to objective test
results. RESULTS: In the noise condition, there was a significant improvement in
the distance of displacement (mean with noise 66.9 cm +/- 33.5 standard
deviation, SD, mean without noise 77.0 cm +/- 32.7 SD, p < 0.001) and in the
angle of rotation (mean with noise 14.2 degrees +/- 10.1 SD, mean without noise
28.3 degrees +/- 20.2 SD, p < 0.001), while no difference was found within the
conditions regarding the angle of displacement (mean with noise 29.1 degrees +/-
33.5 SD, mean without noise 30.0 degrees +/- 34.0 SD, p = 0.641). Side-specific
analysis revealed a positive correlation between angle of displacement and angle
of rotation in the condition without noise (Spearman r = 0.441, p < 0.001). The
rate of agreement between subjective estimation of noise influence and objective
test results ranged between only 43% and 63%, depending on the question and
endpoint. CONCLUSION: Hearing had a clearly beneficial effect of auditory inputs
on vestibulospinal coordination, especially for distance of displacement and
angle of rotation.
PMID- 29947857
TI - [Submucous cleft palate and a congenitally short velum: effects of surgical
intervention].
AB - BACKGROUND: A submucous cleft palate and a congenitally short velum are diagnosed
rather late, because symptoms are often mild. OBJECTIVES: The pre- and
postoperative clinical symptoms for both conditions are presented. MATERIALS AND
METHODS: The data of 180 patients with a submucous cleft palate (161) or
congenitally short velum (19) were retrospective analyzed. In 23.3%, a syndromic
association was found. RESULTS: Clinical findings for both conditions included
middle ear problems, hypernasal speech, nasal penetration, the absence of the
posterior nasal spine of the hard palate and/or a bifid uvula with a zona
pellucida. The average age at diagnosis was 4.2 years in submucous clefts and 5.7
years in children with a congenitally short velum. Surgical palatoplasty with
fusion of soft palate muscles and/or elongation of the soft palate was performed
in 83.9% of the children, aiming to achieve sufficient velopharyngeal closure
(VPC) with a significant decrease of symptoms and, hence, better conditions for
speech therapy interventions. The overall success rate of the VPC was 63.7% with
improvement in up to 2 of the 3 clinical symptoms (hypernasal speech, nasal
penetration, middle ear problems). Hypernasal speech was more common (in 89.5%)
in children with a congenitally short velum before surgery and in 81.3% 8 weeks
after surgery; however, prior to surgery they had a short soft palate.
CONCLUSION: Surgical intervention was particularly effective in children younger
than 5 years. Syndromic diseases are disproportionately associated with soft
palate defects.
PMID- 29947858
TI - What is the process by which a decision to administer electroconvulsive therapy
(ECT) or not is made? A grounded theory informed study of the multi-disciplinary
professionals involved.
AB - PURPOSE: To develop a grounded theory-informed model explaining the decision
making process professionals in multi-disciplinary teams go through in deciding
whether to administer electroconvulsive therapy (ECT) or not. METHODS: A grounded
theory informed methodology was used to analyse the data offered by ten
participants who had all been involved in the process of deciding if someone has
ECT or not. RESULTS: The core categories, described as 'layers' in this research,
'personal and professional identity'; 'subjective vs objective'; 'Guidelines or
Clinical Instinct?'; 'Someone has to take Responsibility' and 'the decision in
action', were constructed from the data. CONCLUSIONS: The study describes a
useful insight into the layers of the decision-making process that could be
further considered in clinical settings. The model highlights the decision to
give ECT that has many different layers including professional identity, how a
person understands the evidence base, past experiences, and the amount of power
they have in the process. The consultant psychiatrist and the patient were seen
as holding most power in the process depending on whether the Mental Capacity Act
(2005) or Mental Health Act (2007) was being followed. Patients were seen to
experience a very different decision-making process dependant on the personal
views of the professionals in relation to ECT.
PMID- 29947859
TI - Correction to: Depressive symptom trajectories in the first 10 years of diabetes
diagnosis: antecedent factors and link with future disability in Taiwan.
AB - The original article can be found online at.
PMID- 29947860
TI - Longitudinal patterns of PTSD symptom classes among US National Guard service
members during reintegration.
AB - PURPOSE: The purpose of this study was to identify posttraumatic stress disorder
(PTSD) symptom groups and assess their longitudinal progression during their
first year of reintegration among United States (US) National Guard (NG) service
members. METHODS: A cohort of NG service members (n = 886) completed surveys at 6
and 12 months following their return from deployment to Iraq or Afghanistan.
Latent class analysis (LCA) and latent transition analysis (LTA) were used to
empirically derive groups based on their PTSD symptoms and examine their
longitudinal course, respectively. RESULTS: The best fitting model at both
assessments was the four-class model, comprising an asymptomatic class (6 months
= 54%; 12 months = 55%), a mild symptom class with elevated hyperarousal symptoms
(6 months = 22%; 12 months = 17%), a moderate symptom class (6 months = 15%; 12
months = 15%), and a severe symptom class (6 months = 10%; 12 months = 13%).
Based on LTA, stability of class membership at the two assessments was 0.797 for
the asymptomatic class, 0.453 for the mild class, 0.560 for the moderate class,
and 0.580 for the severe class. Estimated transition probabilities were greater
with respect to transitioning to less severe, rather than more severe, classes
over time. CONCLUSIONS: The four latent PTSD classes were distinguished primarily
by severity; however, the mild symptom class was characterized by higher levels
of hyperarousal than other symptoms. Although the absolute number of individuals
within classes remained fairly constant between 6 and 12 months, there was
movement between severity classes. Most NG service members without symptoms
continued to do well during the first year, with only an estimated 7% moving to
the moderate or severe class.
PMID- 29947861
TI - School poverty and the risk of attempted suicide among adolescents.
AB - PURPOSE: Existing theory and empirical work suggest that impoverished school
contexts may increase the risk of mental health problems such as suicide. This
study tests this hypothesis by investigating the longitudinal association between
school income and attempted suicide among American adolescents. METHODS: Logistic
regression models were used to estimate the association between school income and
suicidal attempts among all adolescents and among those with suicidal thoughts,
respectively. Data come from the National Longitudinal Survey of Adolescent
Health, a nationally representative sample of American adolescents across 132
middle and high schools (N = 12,920). RESULTS: Among all adolescents, the
prevalence of attempted suicide was higher in low-income schools compared to
middle-income schools for boys but not girls. Among those with suicidal thoughts,
the prevalence of attempted suicide was also higher in low-income schools
compared to middle- and high-income schools for boys only. Differences between
middle- and high-income schools were not observed, suggesting that school income
may only impact attempted suicide when high levels of deprivation are present.
These significant associations persisted after adjusting for established risk
factors such as prior suicidal attempts. CONCLUSION: Highly impoverished school
contexts may increase the risk of attempted suicide for boys. Future research
exploring the mechanisms underlying this association may help inform the
development of more effective suicide-prevention interventions.
PMID- 29947862
TI - Functional impairment among people with severe and enduring mental disorder in
rural Ethiopia: a cross-sectional study.
AB - PURPOSE: Evidence regarding functional impairment in people with severe mental
disorders (SMD) is sparse in low- and middle-income countries. The aim of this
study was to identify factors associated with functional impairment in people
with enduring SMD in a rural African setting. METHODS: A cross-sectional study
was conducted at the baseline of a health service intervention trial. A total of
324 participants were recruited from an existing community-ascertained cohort of
people with SMD (n = 218), and attendees at the Butajira General Hospital
psychiatric clinic (n = 106). Inclusion criteria defined people with SMD who had
ongoing need for care: those who were on psychotropic medication, currently
symptomatic or had a relapse in the preceding 2 years. The World Health
Organization Disability Assessment schedule (WHODAS-2.0) and the Butajira
Functioning Scale (BFS) were used to assess functional impairment. Multivariable
negative binomial regression models were fitted to investigate the association
between demographic, socio-economic and clinical characteristics, and functional
impairment. RESULTS: Increasing age, being unmarried, rural residence, poorer
socio-economic status, symptom severity, continuous course of illness, medication
side effects, and internalized stigma were associated with functional impairment
across self-reported and caregiver responses for both the WHODAS and the BFS.
Diagnosis per se was not associated consistently with functional impairment.
CONCLUSION: To optimize functioning in people with chronic SMD in this setting,
services need to target residual symptoms, poverty, medication side effects, and
internalized stigma. Testing the impact of community interventions to promote
recovery will be useful. Advocacy for more tolerable treatment options is
warranted.
PMID- 29947863
TI - Associations between untreated depression and secondary health care utilization
in patients with hypertension and/or diabetes.
AB - PURPOSE: We determined the prevalence of untreated depression in patients with
hypertension (HT) and/or diabetes (DM) and estimated the extra health care use
and expenditures associated with this comorbidity in a rural Hungarian adult
population. We also assessed the potential workload of systematic screening for
depression in this patient group. METHODS: General health check database from a
primary care programme containing survey data of 2027 patients with HT and/or DM
was linked to the outpatient secondary care use database of National Institute of
Health Insurance Fund Management. Depression was ascertained by Beck Depression
Inventory score and antidepressant drug use. The association between untreated
depression and secondary healthcare utilization indicated by number of visits and
expenses was evaluated by multiple logistic regression analysis controlled for
socioeconomic/lifestyle factors and comorbidity. The age-, sex- and education
specific observations were used to estimate the screening workload for an average
general medical practice. RESULTS: The frequency of untreated depression was
27.08%. The untreated severe depression (7.45%) was associated with increased
number of visits (OR 1.60, 95% CI 1.11-2.31) and related expenses (OR 2.20, 95%
CI 1.50-3.22) in a socioeconomic status-independent manner. To identify untreated
depression cases among patients with HT and/or DM, an average GP has to screen 42
subjects a month. CONCLUSION: It seems to be reasonable and feasible to screen
for depression in patients with HT and/or DM in the primary care, in order to
detect cases without treatment (which may be associated with increase of
secondary care visits and expenditures) and to initiate the adequate treatment of
them.
PMID- 29947864
TI - Cost-effective but clinically inappropriate: new NICE intervention thresholds in
osteoporosis (Technology Appraisal 464).
AB - PURPOSE: To comment on the latest technology appraisal of the National Institute
for Clinical Excellence (NICE) in osteoporosis. METHODS: Review of NICE
Technology Appraisal (TA464) on bisphosphonate use in osteoporosis. RESULTS: The
NICE appraisal on bisphosphonate use in osteoporosis indicates that treatment
with oral bisphosphonates may be instituted at a FRAX 10-year probability of
major osteoporotic fracture above 1%. Implementation would mean that all women
aged 50 years or older are deemed eligible for treatment, a position that would
increase the burden of rare long-term side effects across the population.
CONCLUSION: Cost-effectiveness thresholds for low-cost interventions should not
be used to set intervention thresholds but rather to validate the implementation
of clinically driven intervention thresholds.
PMID- 29947865
TI - Abnormal microarchitecture and stiffness in postmenopausal women using chronic
inhaled glucocorticoids.
AB - : Postmenopausal (PM) women using inhaled glucocorticoids (IGCs) had substantial
abnormalities in volumetric BMD (vBMD), microarchitecture, and stiffness using
high resolution peripheral computed tomography (HRpQCT) compared to age- and race
matched controls. Abnormalities were most severe at the radius. These preliminary
results suggest that there may be major, heretofore unrecognized, skeletal
deficits in PM women using IGCs. INTRODUCTION: While oral glucocorticoids are
well recognized to have destructive skeletal effects, less is known about the
effects of IGCs. The detrimental skeletal effects of IGCs may be greatest in PM
women, in whom they compound negative effects of estrogen loss and aging. The
goal of this study was to evaluate microarchitecture and stiffness in PM women
using chronic IGCs. METHODS: This case-control study compared PM women using IGCs
for >= 6 months (n = 20) and controls matched for age and race/ethnicity (n =
60). Skeletal parameters assessed included areal BMD (aBMD) by DXA, trabecular
and cortical vBMD and microarchitecture by HRpQCT of the radius and tibia, and
whole bone stiffness by finite element analysis. RESULTS: By DXA, mean values in
both groups were in the osteopenic range; hip aBMD was lower in IGC users (P <
0.04). By HRpQCT, IGC users had lower total, cortical, and trabecular vBMD at
both radius and tibia (all P < 0.05). IGC users had lower cortical thickness,
lower trabecular number, greater trabecular separation and heterogeneity at the
radius (all P < 0.03), and greater heterogeneity at the tibia (P < 0.04). Whole
bone stiffness was lower in IGC users at radius (P < 0.03) and tended to be lower
at the tibia (P = 0.09). CONCLUSIONS: PM women using IGCs had substantial
abnormalities in vBMD, microarchitecture, and stiffness compared to controls.
These abnormalities were most severe at the radius. These preliminary results
suggest that there may be major, heretofore unrecognized, skeletal deficits in PM
women using IGCs.
PMID- 29947867
TI - Issues of trial selection and subgroup considerations in the recent meta-analysis
of Zhao and colleagues on fracture reduction by calcium and vitamin D
supplementation in community-dwelling older adults.
AB - : Zhao and colleagues are addressing an important question about the efficacy of
calcium and vitamin D on fracture risk reduction among community-dwelling adults
age 50+. However, we are concerned about four aspects of their approach, which
may affect the validity of their conclusions and implications for public health.
INTRODUCTION: We discuss the recent meta-analysis by Zhao and colleagues on the
primary prevention of fractures of calcium and vitamin D as well as their
combination among community-dwelling adults age 50+. METHODS: Zhao and colleagues
included 33 trials that recruited a total of 51,145 community-dwelling
participants age 50 years and older, including any randomized clinical trial with
a placebo or no treatment in the control group. RESULTS: The authors found no
significant association of calcium and/or vitamin D with risk of hip fracture
compared with placebo or no treatment and concluded that the routine use of
calcium, vitamin D, and the combination in community-dwelling older people is not
supported by their findings. We discuss four concerns regarding this meta
analysis, including the target population, the selection of trials with regard to
blinding and duration of follow-up, and the lack of adjustment for adherence to
the interventions and subgroup analysis by bolus versus daily dosing for vitamin
D. CONCLUSION: Based on the four concerns raised in this letter and the fact that
there will be a manyfold increase in the data on vitamin D supplementation in
community-dwelling senior adults from large ongoing trials, we believe that it is
too early to recommend the cessation of vitamin D with or without calcium for the
prevention of fractures among community-dwelling adults.
PMID- 29947868
TI - Progression of frailty and prevalence of osteoporosis in a community cohort of
older women-a 10-year longitudinal study.
AB - : In community dwelling, 75-year-old women followed 10 years, a frailty index was
created at each of three visits. Frailty score increased by ~ 6-7% annually. A
higher frailty score was equivalent to being 5-10 years chronologically older.
Frailty was associated with low bone density and higher risk of dying.
INTRODUCTION: To understand the distribution of frailty among a population-based
sample of older community-dwelling women, progression over 10 years, and
association with mortality and osteoporosis. METHODS: The study is performed in a
cohort designed to investigate osteoporosis. The OPRA cohort consists of 75-year
old women, n = 1044 at baseline, and follow-up at age 80 and 85. A frailty index
(scored from 0.0-1.0) based on deficits in health across multiple domains was
created at all time-points; outcomes were mortality up to 15 years and femoral
neck bone density. RESULTS: At baseline, the proportion least frail, i.e., most
robust (FI 0.0-0.1) constituted 48%, dropping to 25 and 14% at age 80 and 85. On
average, over 10 years, the annual linear frailty score progression was
approximately 6-7%. Among the least frail, 11% remained robust over 10 years. A
higher frailty score was equivalent to being 5 to 10 years older. Mortality was
substantially higher in the highest quartile compared to the lowest based on
baseline frailty score; after 10 years, 48.7% had died vs 17.2% (p = 1.7 * 10
14). Mortality risk over the first 5 years was highest in the frailest (Q4 vs Q1;
HRunadj 3.26 [1.86-5.73]; p < 0.001) and continued to be elevated at 10 years
(HRunadj 3.58 [2.55-5.03]; p < 0.001). Frailty was associated with BMD after
adjusting for BMI (overall p = 0.006; Q1 vs Q4 p = 0.003). CONCLUSIONS: The
frailty index was highly predictive of mortality showing a threefold increased
risk of death in the frailest both in a shorter and longer perspective. Only one
in ten older women escaped progression after 10 years. Frailty and osteoporosis
were associated.
PMID- 29947866
TI - Skeletal accumulation of fluorescently tagged zoledronate is higher in animals
with early stage chronic kidney disease.
AB - : This work examines the skeletal accumulation of fluorescently tagged
zoledronate in an animal model of chronic kidney disease. The results show higher
accumulation in 24-h post-dose animals with lower kidney function due to greater
amounts of binding at individual surfaces. INTRODUCTION: Chronic kidney disease
(CKD) patients suffer from increased rates of skeletal-related mortality from
changes driven by biochemical abnormalities. Bisphosphonates are commonly used in
reducing fracture risk in a variety of diseases, yet their use is not recommended
in advanced stages of CKD. This study aimed to characterize the accumulation of a
single dose of fluorescently tagged zoledronate (FAM-ZOL) in the setting of
reduced kidney function. METHODS: At 25 weeks of age, FAM-ZOL was administered to
normal and CKD rats. Twenty-four hours later, multiple bones were collected and
assessed using bulk fluorescence imaging, two-photon imaging, and dynamic
histomorphometry. RESULTS: CKD animals had significantly higher levels of FAM-ZOL
accumulation in the proximal tibia, radius, and ulna, but not in lumbar vertebral
body or mandible, based on multiple measurement modalities. Although a majority
of trabecular bone surfaces were covered with FAM-ZOL in both normal and CKD
animals, the latter had significantly higher levels of fluorescence per unit bone
surface in the proximal tibia. CONCLUSIONS: These results provide new data
regarding how reduced kidney function affects drug accumulation in rat bone.
PMID- 29947869
TI - Characteristics of recurrent fractures.
AB - : The present study, drawn from a sample of the Icelandic population, quantified
high immediate risk and utility loss of subsequent fracture after a sentinel
fracture (at the hip, spine, distal forearm and humerus) that attenuated with
time. INTRODUCTION: The risk of a subsequent osteoporotic fracture is
particularly acute immediately after an index fracture and wanes progressively
with time. The aim of this study was to quantify the risk and utility
consequences of subsequent fracture after a sentinel fracture (at the hip, spine,
distal forearm and humerus) with an emphasis on the time course of recurrent
fracture. METHODS: The Reykjavik Study fracture registration, drawn from a sample
of the Icelandic population (n = 18,872), recorded all fractures of the
participants from their entry into the study until December 31, 2012. Medical
records for the participants were manually examined and verified. First sentinel
fractures were identified. Subsequent fractures, deaths, 10-year probability of
fracture and cumulative disutility using multipliers derived from the
International Costs and Utilities Related to Osteoporotic fractures Study
(ICUROS) were examined as a function of time after fracture, age and sex.
RESULTS: Over 10 years, subsequent fractures were sustained in 28% of 1498
individuals with a sentinel hip fracture. For other sentinel fractures, the
proportion ranged from 35 to 38%. After each sentinel fracture, the risk of
subsequent fracture was highest in the immediate post fracture interval and
decreased markedly with time. Thus, amongst individuals who sustained a recurrent
fracture, 31-45% did so within 1 year of the sentinel fracture. Hazard ratios for
fracture recurrence (population relative risks) were accordingly highest
immediately after the sentinel fracture (2.6-5.3, depending on the site of
fracture) and fell progressively over 10 years (1.5-2.2). Population relative
risks also decreased progressively with age. The utility loss during the first 10
years after a sentinel fracture varied by age (less with age) and sex (greater in
women). In women at the age of 70 years, the mean utility loss due to fractures
in the whole cohort was 0.081 whereas this was 12-fold greater in women with a
sentinel hip fracture, and was increased 15-fold for spine fracture, 4-fold for
forearm fracture and 8-fold for humeral fracture. CONCLUSION: High fracture risks
and utility loss immediately after fracture suggest that treatment given as soon
as possible after fracture would avoid a higher number of new fractures compared
with treatment given later. This provides the rationale for very early
intervention immediately after a sentinel fracture.
PMID- 29947870
TI - Tracking of bone mass from childhood to puberty: a 7-year follow-up. The CHAMPS
study DK.
AB - : Bone mass in childhood is highly influenced by puberty. At the same age, bone
mass was higher for pubertal than pre-pubertal children. A high level of tracking
during 7 years from childhood through puberty was shown, indicating that early
levels of bone mass may be important for later bone health. INTRODUCTION: Bone
mass development in childhood varies by sex and age, but also by pubertal stage.
The objectives of this study were to (1) describe bone mass development in
childhood as it relates to pubertal onset and to (2) determine the degree of
tracking from childhood to adolescence. METHODS: A longitudinal study with 7
years of follow-up was initiated in 2008 to include 831 children (407 boys) aged
8 to 17 years. Participants underwent whole body dual-energy X-ray absorptiometry
(DXA) scanning, blood collection to quantify luteinizing hormone levels, and
Tanner stage self-assessment three times during the 7-year follow-up. Total body
less head bone mineral content, areal bone mineral density, and bone area were
used to describe development in bone accrual and to examine tracking over 7
years. RESULTS: Bone mass in pubertal children is higher than that of pre
pubertal children at the same age. Analysing tracking with quintiles of bone mass
Z-scores in 2008 and 2015 showed that more than 80% of participants remained in
the same or neighbouring quintile over the study period. Tracking was confirmed
by correlation coefficients between Z-scores at baseline and 7-year follow-up
(range, 0.80-0.84). CONCLUSIONS: Bone mass is highly influenced by pubertal
onset, and pubertal stage should be considered when examining children's bone
health. Because bone mass indices track from childhood into puberty, children
with low bone mass may be at risk of developing osteoporosis later in life.
PMID- 29947871
TI - Abnormal bone turnover in individuals with low serum alkaline phosphatase.
AB - The clinical spectrum of hypophosphatasia (HPP) is broad and variable within
families. Along severe infantile forms, adult forms with mild manifestations may
be incidentally discovered by the presence of low alkaline phosphatase (ALP)
activity in serum. However, it is still unclear whether individuals with
persistently low levels of ALP, in the absence of overt manifestations of HPP,
have subclinical abnormalities of bone remodeling or bone mass. The aim of this
study was to obtain a better understanding of the skeletal phenotype of adults
with low ALP by analyzing bone mineral density (BMD), bone microarchitecture
(trabecular bone score, TBS), and bone turnover markers (P1NP and beta
crosslaps). We studied 42 individuals with persistently low serum ALP. They
showed lower levels of P1NP (31.4 +/- 13.7 versus 48.9 +/- 24.4 ng/ml; p =
0.0002) and beta-crosslaps (0.21 +/- 0.17 versus 0.34 +/- 0.22 ng/ml, p = 0.0015)
than individuals in the control group. There were no significant differences in
BMD, bone mineral content, or TBS. These data suggest that individuals with
hypophosphatasemia have an overall reduction of bone turnover, even in the
absence of overt manifestations of HPP or low BMD. We evaluated bone mineral
density (BMD), bone microarchitecture, and bone turnover markers in patients with
low serum levels of alkaline phosphatase. Our results show that these patients
have low bone remodeling even in the absence of BMD abnormalities, thus
supporting the recommendation of avoiding antiresorptives such as bisphosphonates
in these subjects.
PMID- 29947872
TI - Dietary fat, saturated fatty acid, and monounsaturated fatty acid intakes and
risk of bone fracture: a systematic review and meta-analysis of observational
studies.
AB - Total dietary fat intake might influence the risk of fracture; however,
conflicting findings have been reported to date. Moreover, the type of fatty
acids is also of vital importance. We aimed to conduct a comprehensive review of
the literature on the association between dietary fat intake, saturated fatty
acids (SFAs), monounsaturated fatty acids (MUFAs), and the risk of fracture.
PubMed and Scopus were used to conduct a comprehensive search for articles
published up to 7 January 2018. To pool effect sizes, random effects models (the
DerSimonian-Laird method) were applied. The Cochrane Q test was used to trace the
source of between-study heterogeneity. Six studies met inclusion criteria for
meta-analysis. We found no significant association between total dietary fat
intake and risk of fracture (pooled effect size 1.31, 95% confidence interval
(95% CI) 0.95-1.79, P = 0.09). A significant positive association was observed
between SFA intake and the risk of hip fracture (pooled effect size 1.79, 95% CI
1.05-3.03, P = 0.03). There was also a significant positive association between
MUFAs derived from animal sources and the risk of fracture (pooled effect size
2.29, 95% CI 1.50-3.50, P < 0.0001). Our findings showed a strong positive
association between SFAs intake and risk of hip fracture. Moreover, there was a
significant positive association between MUFAs derived from animal sources and
the risk of fracture.
PMID- 29947873
TI - Association of renal function with bone mineral density and fracture risk in the
Longitudinal Aging Study Amsterdam.
AB - : Early renal dysfunction is associated with a 38% increased fracture risk in
individuals aged 65 years and older. In men but not women, early renal
dysfunction is associated with decreased femoral neck bone mineral density (BMD)
which can be partially explained by increased parathyroid hormone (PTH)
concentrations. INTRODUCTION: It is uncertain whether early renal dysfunction is
associated with osteoporosis and increased fracture risk. The aim of this study
was to determine the relationship of decreased renal function with BMD and
fracture risk and the role of PTH therein. METHODS: We analyzed data of
participants aged 65 years and older from the Longitudinal Aging Study Amsterdam.
A 6-year fracture follow-up was obtained in 1477 participants. BMD was measured
by dual-energy x-ray absorptiometry (n = 535) and vertebral fractures by lateral
spinal radiograph (n = 527) in a subsample at baseline. Glomerular filtration
rate (eGFR) was estimated according to the modification of diet in renal disease
equation and assessed by the five stages of chronic kidney disease (CKD).
RESULTS: In men and women, eGFR < 57 ml/min/1.73 m2 (lowest quartile) compared to
eGFR > 74 ml/min/1.73 m2 (highest quartile) was associated with a 38% increase in
fracture risk after adjustment for relevant confounders [hazard ratio (95%CI):
1.38 (1.17 to 1.61)]. Also, CKD stages 3a and 3b were associated to a 28 and 46%
increase in fracture risk, respectively, as compared to CKD stages 1 and 2
together (eGFR > 60 ml/min/1.73 m2) after adjustment for confounders. Renal
function was not associated with prevalent vertebral fractures. In men, but not
women, lowest quartile of eGFR was related to lower femoral neck BMD as compared
to the highest quartile eGFR [unstandardized B (95%CI) - 0.052 g/cm2 (- 0.098 to
0.006)], after adjustment for relevant confounders. Further adjustment for PTH
attenuated this relationship by 27%. CONCLUSIONS: In men and women, early
decreased renal function (eGFR < 60 ml/min/1.73 m2) was related to increased
incident any fracture risk but not with increased prevalence of vertebral
fractures. In men, but not women, early renal dysfunction was related to lower
femoral neck BMD which could statistically be partially explained by increased
PTH concentrations.
PMID- 29947874
TI - [Bone cysts-differential diagnosis and therapeutic approach].
AB - The differential diagnosis of cystic lesions of the skeleton is multifarious.
Besides patient age, the localization and radiologic morphology provide important
information for a closer differentiation. Juvenile and aneurysmal bone cysts
represent two frequent entities in growing patients. The fluid content of the
cysts helps in distinguishing between juvenile and aneurysmal bone cysts. Whereas
juvenile bone cysts contain clear fluid, the content of aneurysmal bone cysts
consists of blood combined with solid tissue. With respect to progression,
aneurysmal bone cysts show a higher activity than solitary bone cysts. The
treatment of juvenile bone cysts usually consists of curettage including filling
with bone replacement material. For aneurysmal bone cysts the additional use of
adjuvants is recommended. Bone cement is preferably used for filling. It shows
favorable properties for prophylaxis of recurrence and facilitates the
recognition of relapses. Both juvenile and aneurysmal bone cysts often show
recurrences.
PMID- 29947875
TI - [Treatment of the ulnar impingement syndrome in the distal radioulnar joint].
AB - Ligamentous stability and joint congruity are prerequisites for a physiological
function of the distal radioulnar joint (DRUJ). Impingement of the ulnar head may
be caused by a congenital ulna-minus variance or by an iatrogenically excessive
ulna shortening osteotomy. This impingement is detected by a positive compression
test at the DRUJ. Radius correction osteotomy with shortening and correction of
the radial inclination to restore the sigmoid notch may solve the problem by
reducing the pressure between both joint partners and by promoting the
remodelling of the DRUJ. This technique may restore the distal radioulnar joint
and thus prevent the necessity of salvage procedures.
PMID- 29947877
TI - [5-year follow-up of 210 Columbus knee prostheses : A prospective multicentre
study].
AB - INTRODUCTION: As part of 10-year documentation using the Columbus system, the
interim evaluation was carried out 5 years after implantation with a collection
of clinical scores, evaluation of radiological imaging and collection of
statistics concerning complications. METHODS: There was a multicentre prospective
recruitment of consecutive patients with the indication of implantation of a
surface replacement prosthesis (Columbus CR, Deep Dish fixed inlay).
Preoperatively, clinical scores were recorded (KSS and Oxford score). Five years
postoperatively a new evaluation of clinical scores, the range of motion (ROM)
and a radiological check-up including full leg imaging under load was performed.
During this period, detailed complication documentation was made. RESULTS: A
total of 210 patients were recruited in five centres. 187 patients were available
for examination 5 years after surgery. Cumulative KSS increased from 87.5 (+/
26.6) preoperatively to 170 (+/-29.1) 5 years postoperatively. The cumulative KSS
improvement was 81.5 (+/-35.2) points and was highly significant (p < 0.0001; t
test). The average functional improvement in the Oxford score between the
preoperative and 5-year follow-up was 21.7 (+/-8.8) points and was also highly
significant (p < 0.0001). The ROM improved from 106.3 degrees (+/-20.2)
preoperatively to 114.0 degrees (+/-12.1) 5 years postoperatively (p < 0.0001; t
test). Five years after implantation, the average mechanical leg axis was 178.0
degrees (+/-2.1). There was no clinically apparent or native radiologic visible
aseptic loosening of the femoral or tibial joint component. There were 33
complications, but no implant-related complications such as inlay dislocation,
material fracture or aseptic loosening. In total, 6 revision surgeries were
performed during the follow-up period, which corresponds to a survival rate of
97.1% (CI 95%) for the implanted Columbus knee in the present patient collective
for 5 years. CONCLUSION: The interim analysis at 5 years of long-term observation
of the Columbus system provided good clinical and radiographic results.
PMID- 29947876
TI - [The proximal radioulnar joint in consideration of the distal radioulnar joint].
AB - The movement of the forearm follows a complex interplay of three main components:
the proximal and distal radioulnar joint and the interosseous membrane. Injuries
to one or even all components have a huge impact on the integrity of this system.
The Essex-Lopresti lesion presented a high challenge in clinical diagnostics as
well as therapy. Reconstructions of the length and stability are essential for a
satisfactory postoperative outcome. If a reconstruction of the radial head by
osteosynthesis is not possible, a radial head prosthesis should be implanted in
the case of longitudinal instability - avoiding overlapping and/or oversizing.
The reconstruction of the interosseous membrane should be considered, as well as
the assessment of the distal radioulnar joint and/or the triangular
fibrocartilage complex. Various reconstruction options are available in this
regard.
PMID- 29947878
TI - Unilateral orolingual angioedema after thrombolysis in a patient with
cerebrovascular ischemia.
PMID- 29947879
TI - Do trials that report a neutral or negative treatment effect improve the care of
critically ill patients? No.
PMID- 29947881
TI - An unexpected blood thief: the subacute presentation of a spontaneous Ilio-iliac
arterio-venous fistula.
PMID- 29947880
TI - Do trials that report a neutral or negative treatment effect improve the care of
critically ill patients? Yes.
PMID- 29947882
TI - Out of the ICU shifting as a significant workload.
PMID- 29947883
TI - Cardiac output drives tolerance of acute hemolysis.
PMID- 29947884
TI - Sepsis: who will shoot first? Pharma or diagnostics?
PMID- 29947885
TI - Correction to: Should all ICU clinicians regularly be tested for burnout? No.
AB - The original publication contained an erroneous version of Fig. 1.
PMID- 29947886
TI - What's new in severe pulmonary embolism?
PMID- 29947887
TI - Estimation of true driving pressure during airway pressure release ventilation :
Discussion on "Early application of airway pressure release ventilation may
reduce the duration of mechanical ventilation in acute respiratory distress
syndrome".
PMID- 29947888
TI - Impact of the driving pressure on mortality in obese and non-obese ARDS patients:
a retrospective study of 362 cases.
AB - PURPOSE: The relation between driving pressure (plateau pressure-positive end
expiratory pressure) and mortality has never been studied in obese ARDS patients.
The main objective of this study was to evaluate the relationship between 90-day
mortality and driving pressure in an ARDS population ventilated in the intensive
care unit (ICU) according to obesity status. METHODS: We conducted a
retrospective single-center study of prospectively collected data of all ARDS
patients admitted consecutively to a mixed medical-surgical adult ICU from
January 2009 to May 2017. Plateau pressure, compliance of the respiratory system
(Crs) and driving pressure of the respiratory system within 24 h of ARDS
diagnosis were compared between survivors and non-survivors at day 90 and between
obese (body mass index >= 30 kg/m2) and non-obese patients. Cox proportional
hazard modeling was used for mortality at day 90. RESULTS: Three hundred sixty
two ARDS patients were included, 262 (72%) non-obese and 100 (28%) obese
patients. Mortality rate at day 90 was respectively 47% (95% CI, 40-53) in the
non-obese and 46% (95% CI, 36-56) in the obese patients. Driving pressure at day
1 in the non-obese patients was significantly lower in survivors at day 90 (11.9
+/- 4.2 cmH2O) than in non-survivors (15.2 +/- 5.2 cmH2O, p < 0.001). Contrarily,
in obese patients, driving pressure at day 1 was not significantly different
between survivors (13.7 +/- 4.5 cmH2O) and non-survivors (13.2 +/- 5.1 cmH2O, p =
0.41) at day 90. After three multivariate Cox analyses, plateau pressure [HR =
1.04 (95% CI 1.01-1.07) for each point of increase], Crs [HR = 0.97 (95% CI 0.96
0.99) for each point of increase] and driving pressure [HR = 1.07 (95% CI 1.04
1.10) for each point of increase], respectively, were independently associated
with 90-day mortality in non-obese patients, but not in obese patients.
CONCLUSIONS: Contrary to non-obese ARDS patients, driving pressure was not
associated with mortality in obese ARDS patients.
PMID- 29947889
TI - Prenatal arsenic exposure is associated with increased plasma IGFBP3
concentrations in 9-year-old children partly via changes in DNA methylation.
AB - Exposure to inorganic arsenic (As), a carcinogen and epigenetic toxicant, has
been associated with lower circulating levels of insulin-like growth factor 1
(IGF1) and impaired growth in children of pre-school age. The aim of this study
was to assess the potential impact of exposure to As on IGF1 and insulin-like
growth factor-binding protein 3 (IGFBP3) as well as DNA methylation changes in 9
year-old children. To this end, we studied 9-year-old children from a
longitudinal mother-child cohort in rural Bangladesh (n = 551). Prenatal and
concurrent exposure to As was assessed via concentrations in maternal urine at
gestational week 8 and in child urine at 9 years, measured by HPLC-HG-ICPMS.
Plasma IGF1 and IGFBP3 concentrations were quantified with immunoassays. DNA
methylation was measured in blood mononuclear cells at 9 years in a sub-sample (n
= 113) using the Infinium HumanMethylation450K BeadChip. In multivariable
adjusted linear regression models, prenatal As (natural log-transformed), but not
children's concurrent urinary As, was positively associated with IGFBP3
concentrations (beta = 76, 95% CI 19, 133). As concentrations were not associated
with IGF1. DNA methylation analysis revealed CpGs associated with both prenatal
As and IGFBP3. Mediation analysis suggested that methylation of 12 CpG sites for
all children was mediator of effect for the association between prenatal As and
IGFBP3. We also found differentially methylated regions, generally
hypermethylated, that were associated with both prenatal As and IGFBP3. In all,
our study revealed that prenatal exposure to As was positively associated with
IGFBP3 concentrations in children at 9 years, independent of IGF1, and this
association may, at least in part, be epigenetically mediated.
PMID- 29947890
TI - Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed
females in Turkey.
AB - Boric acid and sodium borates are currently classified as being toxic to
reproduction under "Category 1B" with the hazard statement of "H360 FD" in the
European CLP regulation. This has prompted studies on boron-mediated reprotoxic
effects in male workers in boron mining areas and boric acid production plants.
By contrast, studies on boron-mediated developmental effects in females are
scarce. The present study was designed to fill this gap. Hundred and ninety nine
females residing in Bandirma and Bigadic participated in this study investigating
pregnancy outcomes. The participants constituted a study group covering blood
boron from low (< 100 ng B/g blood, n = 143) to high (> 150 ng B/g blood, n = 27)
concentrations. The mean blood boron concentration and the mean estimated daily
boron exposure of the high exposure group was 274.58 (151.81-975.66) ng B/g blood
and 24.67 (10.47-57.86) mg B/day, respectively. In spite of the high level of
daily boron exposure, boron-mediated adverse effects on induced abortion,
spontaneous abortion (miscarriage), stillbirth, infant death, neonatal death,
early neonatal death, preterm birth, congenital anomalies, sex ratio and birth
weight of newborns were not observed.
PMID- 29947891
TI - Sensitization of colorectal cancer cells to irinotecan by the Survivin inhibitor
LLP3 depends on XAF1 proficiency in the context of mutated p53.
AB - Survivin is a well-established target in experimental cancer therapy. While
hardly expressed in normal tissues, it is over-expressed in most human tumors,
including colorectal cancer (CRC). Different compartmentalization of Survivin
enables its multiple functions as a key controller of cell division, apoptosis,
stress-induced signaling and also of migration and metastasis. Because of the
lack of its enzymatic activity, this oncoprotein is considered to be undruggable.
Nevertheless, small-molecule interfacial inhibitors interfering with its
dimerization and/or disrupting the Survivin-Ran protein complex were shown to be
potent drugs causing Survivin proteasomal degradation and inducing apoptosis in
cancer cells. Based on our results with different CRC cell lines, we show that
the Survivin inhibitor LLP3 might be effective as mono-therapy in the subgroup of
p53-proficient and also some p53-mutated tumors, independent of mismatch repair
status. When combined with irinotecan, expression of the tumor suppressor X
linked inhibitor of apoptosis factor 1 (XAF1) plays a decisive role for
sensitization of CRC cells to this first-line drug, however, only in the p53
mutated background. The combination treatment with IT should be avoided in p53
proficient tumors independent of XAF1 expression, since no sensitization to or
even protection against moderate-toxic concentrations of IT might occur.
PMID- 29947892
TI - Perinatal exposure to a glyphosate-based herbicide impairs female reproductive
outcomes and induces second-generation adverse effects in Wistar rats.
AB - Glyphosate-based herbicides (GBHs) are the most globally used herbicides raising
the risk of environmental exposition. Here, we investigated whether perinatal
exposure to low doses of a GBH alters the female reproductive performance, and/or
induced second-generation effects related to congenital anomalies or growth
alterations. Pregnant rats (F0) received a GBH through food, in a dose of 2 mg
(GBH-LD: GBH-low dose group) or 200 mg (GBH-HD: GBH-high dose group) of
glyphosate/kg bw/day from gestational day (GD) 9 until weaning. Body weight gain
and vaginal canal-opening of F1 females were recorded. Sexually mature F1 females
were mated to evaluate their reproductive performance by assessing the pregnancy
rate, and on GD19, the number of corpora lutea, the implantation sites (IS) and
resorption sites. To analyze second-generation effects on F2 offspring, we
analyzed the fetal morphology on GD19, and assessed the fetal length and weight,
and the placental weight. GBH exposure neither altered the body weight gain of F1
females, nor vaginal opening onset. Although all GBH-exposed F1 rats became
pregnant, a lower number of IS was detected. F2 offspring from both GBH groups
showed delayed growth, evidenced by lower fetal weight and length, associated
with a higher incidence of small for gestational age fetuses. In addition, higher
placental weight and placental index were found in F2 offspring from GBH-HD dams.
Surprisingly, structural congenital anomalies (conjoined fetuses and abnormally
developed limbs) were detected in the F2 offspring from GBH-HD group. In
conclusion, perinatal exposure to low doses of a GBH impaired female reproductive
performance and induced fetal growth retardation and structural congenital
anomalies in F2 offspring.
PMID- 29947893
TI - The HDAC6/8/10 inhibitor TH34 induces DNA damage-mediated cell death in human
high-grade neuroblastoma cell lines.
AB - High histone deacetylase (HDAC) 8 and HDAC10 expression levels have been
identified as predictors of exceptionally poor outcomes in neuroblastoma, the
most common extracranial solid tumor in childhood. HDAC8 inhibition synergizes
with retinoic acid treatment to induce neuroblast maturation in vitro and to
inhibit neuroblastoma xenograft growth in vivo. HDAC10 inhibition increases
intracellular accumulation of chemotherapeutics through interference with
lysosomal homeostasis, ultimately leading to cell death in cultured neuroblastoma
cells. So far, no HDAC inhibitor covering HDAC8 and HDAC10 at micromolar
concentrations without inhibiting HDACs 1, 2 and 3 has been described. Here, we
introduce TH34 (3-(N-benzylamino)-4-methylbenzhydroxamic acid), a novel
HDAC6/8/10 inhibitor for neuroblastoma therapy. TH34 is well-tolerated by non
transformed human skin fibroblasts at concentrations up to 25 uM and modestly
impairs colony growth in medulloblastoma cell lines, but specifically induces
caspase-dependent programmed cell death in a concentration-dependent manner in
several human neuroblastoma cell lines. In addition to the induction of DNA
double-strand breaks, HDAC6/8/10 inhibition also leads to mitotic aberrations and
cell-cycle arrest. Neuroblastoma cells display elevated levels of neuronal
differentiation markers, mirrored by formation of neurite-like outgrowths under
maintained TH34 treatment. Eventually, after long-term treatment, all
neuroblastoma cells undergo cell death. The combination of TH34 with plasma
achievable concentrations of retinoic acid, a drug applied in neuroblastoma
therapy, synergistically inhibits colony growth (combination index (CI) < 0.1 for
10 uM of each). In summary, our study supports using selective HDAC inhibitors as
targeted antineoplastic agents and underlines the therapeutic potential of
selective HDAC6/8/10 inhibition in high-grade neuroblastoma.
PMID- 29947894
TI - Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism
dysregulation in HepaRG liver cells exposed to PCB 126.
AB - Chemical pollutant exposure is a risk factor contributing to the growing epidemic
of non-alcoholic fatty liver disease (NAFLD) affecting human populations that
consume a western diet. Although it is recognized that intoxication by chemical
pollutants can lead to NAFLD, there is limited information available regarding
the mechanism by which typical environmental levels of exposure can contribute to
the onset of this disease. Here, we describe the alterations in gene expression
profiles and metabolite levels in the human HepaRG liver cell line, a validated
model for cellular steatosis, exposed to the polychlorinated biphenyl (PCB) 126,
one of the most potent chemical pollutants that can induce NAFLD. Sparse partial
least squares classification of the molecular profiles revealed that exposure to
PCB 126 provoked a decrease in polyunsaturated fatty acids as well as an increase
in sphingolipid levels, concomitant with a decrease in the activity of genes
involved in lipid metabolism. This was associated with an increased oxidative
stress reflected by marked disturbances in taurine metabolism. A gene ontology
analysis showed hallmarks of an activation of the AhR receptor by dioxin-like
compounds. These changes in metabolome and transcriptome profiles were observed
even at the lowest concentration (100 pM) of PCB 126 tested. A decrease in
docosatrienoate levels was the most sensitive biomarker. Overall, our integrated
multi-omics analysis provides mechanistic insight into how this class of chemical
pollutant can cause NAFLD. Our study lays the foundation for the development of
molecular signatures of toxic effects of chemicals causing fatty liver diseases
to move away from a chemical risk assessment based on in vivo animal experiments.
PMID- 29947895
TI - Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics
in whole blood using parallel artificial liquid membrane extraction and UHPLC
MS/MS.
AB - Benzodiazepines (BZD) and Z-hypnotics are frequently analyzed in forensic
laboratories, and in 2012, the designer benzodiazepines (DBZD) emerged on the
illegal drug scene. DBZD represent a particular challenge demanding new
analytical methods. In this work, parallel artificial liquid membrane extraction
(PALME) is used for sample preparation of DBZD, BZD, and Z-hypnotics in whole
blood prior to UHPLC-MS/MS analysis. PALME of BZD, DBZD, and Z-hypnotics was
performed from whole blood samples, and the analytes were extracted across a
supported liquid membrane (SLM) and into an acceptor solution of dimethyl
sulfoxide and 200 mM formic acid (75:25, v/v). The method was validated according
to EMA guidelines. The method was linear throughout the calibration range (R2 >
0.99). Intra- and inter-day accuracy and precision, as well as matrix effects,
were within the guideline limit of +/- 15%. LOD and LLOQ ranged from 0.10 to 5.0
ng mL-1 and 3.2 to 160 ng mL-1, respectively. Extraction recoveries were
reproducible and above 52%. The method was specific, and the analytes were stable
in the PALME extracts for 4 and 10 days at 10 and - 20 degrees C. No carry-over
was observed within the calibration range. PALME and UHPLC-MS/MS for the
determination of DBZD, BZD, and Z-hypnotics in whole blood are a green and low
cost alternative that provides high sample throughput (96-well format), extensive
sample clean-up, good sensitivity, and high reproducibility. The presented method
is also the first method incorporating analysis of DBZD, BZD, and Z-hypnotics in
whole blood in one efficient analysis. Graphical abstract.
PMID- 29947896
TI - Flow field-flow fractionation and multi-angle light scattering as a powerful tool
for the characterization and stability evaluation of drug-loaded metal-organic
framework nanoparticles.
AB - Asymmetric flow field-flow fractionation (AF4) coupled with UV-Vis spectroscopy,
multi-angle light scattering (MALS) and refractive index (RI) detection has been
applied for the characterization of MIL-100(Fe) nanoMOFs (metal-organic
frameworks) loaded with nucleoside reverse transcriptase inhibitor (NRTI) drugs
for the first time. Empty nanoMOFs and nanoMOFs loaded with azidothymidine
derivatives with three different degrees of phosphorylation were examined:
azidothymidine (AZT, native drug), azidothymidine monophosphate (AZT-MP), and
azidothymidine triphosphate (AZT-TP). The particle size distribution and the
stability of the nanoparticles when interacting with drugs have been determined
in a time frame of 24 h. Main achievements include detection of aggregate
formation in an early stage and monitoring nanoMOF morphological changes as
indicators of their interaction with guest molecules. AF4-MALS proved to be a
useful methodology to analyze nanoparticles engineered for drug delivery
applications and gave fundamental data on their size distribution and stability.
Graphical abstract ?.
PMID- 29947897
TI - Mass spectrometry-based proteomics for system-level characterization of
biological responses to engineered nanomaterials.
AB - The widespread use of engineered nanomaterials or nanotechnology makes the
characterization of biological responses to nanomaterials an important area of
research. The application of omics approaches, such as mass spectrometry-based
proteomics, has revealed new insights into the cellular responses of exposure to
nanomaterials, including how nanomaterials interact and alter cellular pathways.
In addition, exposure to engineered nanomaterials often leads to the generation
of reactive oxygen species and cellular oxidative stress, which implicates a
redox-dependent regulation of cellular responses under such conditions. In this
review, we discuss quantitative proteomics-based approaches, with an emphasis on
redox proteomics, as a tool for system-level characterization of the biological
responses induced by engineered nanomaterials. Graphical abstract ?.
PMID- 29947898
TI - A one-pot, isothermal DNA sample preparation and amplification platform utilizing
aqueous two-phase systems.
AB - Infectious diseases remain one of the major causes of death worldwide in
developing countries. While screening via conventional polymerase chain reaction
(PCR) is the gold standard in laboratory testing, its limited applications at the
point-of-care have prompted the development of more portable nucleic acid
detection systems. These include isothermal DNA amplification techniques, which
are less equipment-intensive than PCR. Unfortunately, these techniques still
require extensive sample preparation, limiting user accessibility. In this study,
we introduce a novel system that combines thermophilic helicase-dependent
amplification (tHDA) with a Triton X-100 micellar aqueous two-phase system (ATPS)
to achieve cell lysis, lysate processing, and enhanced nucleic acid amplification
in a simple, one-step process. The combined one-pot system was able to amplify
and detect a target gene from whole-cell samples containing as low as 102 cfu/mL,
and is the first known application of ATPSs to isothermal DNA amplification. This
system's ease-of-use and sensitivity underlie its potential as a point-of-care
diagnostic platform to detect for infectious diseases. Graphical abstract ?.
PMID- 29947899
TI - Fully automated sample preparation procedure to measure drugs of abuse in plasma
by liquid chromatography tandem mass spectrometry.
AB - For the analysis of drugs and pharmaceutical compounds in biological matrices,
extraction procedures are typically used for LC-MS/MS analysis often requiring
manual steps in sample preparation. In this study, we report a fully automated
extraction method carried out by a programable liquid handler directly coupled to
an LC-MS/MS system for the determination of 42 components (illicit drugs and/or
metabolites) (plus 20 deuterated internal standards). The acquisition was
performed in positive ionization mode with up to 15 MRM transitions per compound,
each with optimized collision energy (MRM spectrum mode) to enable qualitative
library searching in addition to quantitation. After placing the sample tube into
the system, no further intervention was necessary: automated preparation used 50
MUL of blood or plasma with 3 MUL of extracted sample injected for analysis. The
method was validated according to the requirements of ISO 15189. The limit of
detection and quantification was 1-5 ng/mL depending on the compound. Stability
experiments found that historic calibration curve data files could accurately
quantify for up to 1 month with less than 20% uncertainty. Comparison to a
QuEChERS method was made using patient samples providing a regression correlation
R2 = 0.98 between the two methods. This approach was successfully designed to
support parallel sample preparation and analysis therefore significantly
increasing sample throughput and reduced cycle times. Graphical abstract ?.
PMID- 29947900
TI - Development and validation of LC/APCI-MS method for the quantification of oat
ceramides in skin permeation studies.
AB - Ceramides (CERs) are the backbone of the intercellular lipid lamellae of the
stratum corneum (SC), the outer layer of the skin. Skin diseases such as atopic
dermatitis, psoriasis, and aged skin are characterized by dysfunctional skin
barrier and dryness which are associated with reduced levels of CERs.
Replenishing the depleted epidermal CERs with exogenous CERs has been shown to
have beneficial effects in improving the skin barrier and hydration. The
exogenous CERs such as phyto-derived CERs (PhytoCERs) can be delivered deep into
the SC using novel topical formulations. This, however, requires investigating
the rate and extent of skin permeation of CERs. In this study, an LC/APCI-MS
method to detect and quantify PhytoCERs in different layers of the skin has been
developed and validated. The method was used to investigate the skin permeation
of PhytoCERs using Franz diffusion cells after applying an amphiphilic cream
containing PhytoCERs to the surface of ex vivo human skin. As plant-specific CERs
are not commercially available, well-characterized CERs isolated from oat (Avena
abyssinica) were used as reference standards for the development and validation
of the method. The method was linear over the range of 30-1050 ng/mL and
sensitive with limit of detection and quantification of 10 and 30 ng/mL,
respectively. The method was also selective, accurate, and precise with minimal
matrix effect (with mean matrix factor around 100%). Even if more than 85% of oat
CERs in the cream remained in the cream after the incubation periods of 30, 100,
and 300 min, it was possible to quantify the small quantities of oat CERs
distributed across the SC, epidermis, and dermis of the skin indicating the
method's sensitivity. Therefore, the method can be used to investigate the skin
permeation of oat CERs from the various pharmaceutical and cosmeceutical products
without any interference from the skin constituents such as the epidermal lipids.
Graphical abstract ?.
PMID- 29947901
TI - Antigen-free control wells in an ELISA set-up for the determination of
autoantibodies against G protein-coupled receptors-a requisite for correct data
evaluation.
AB - First functional acting autoantibodies against G protein-coupled receptors such
as the beta2-adrenoceptor in e.g. asthmatic patients have already been discovered
in the early 1980s of the last century using assays that show their functional
activity. Today, almost 40 years later, the measurement of such autoantibodies is
still a challenge. Bioassays able to show the functional activity of such
autoantibodies against G protein-coupled receptors are still the ne plus ultra
for their detection and also classification when additionally exploiting specific
receptor blockers for the neutralisation of the effect. Bioassays based on living
cells make specific demands on the laboratories and are, therefore not suitable
for every routine laboratory. Routine diagnostics, therefore, ideally requires
different assays based on e.g. solid-phase technology, such as enzyme-linked
immunosorbent assay (ELISA) technology. Here, endeavours are going on, using
either the exact epitopes of such autoantibodies, if known, for trapping the
autoantibodies, or the complete receptor in biological or artificial membranes
that are immobilised onto a plastic carrier (ELISA principle). Here, we question
and discuss the outcome of such tests, especially, if no controls such as the non
coated plastic carrier or the corresponding receptor-free membrane coat is
offered as control in parallel, in light of the manifold experiences already
collected with even non-agonistic acting autoantibodies by Guven et al. (J
Immunol Methods 403:26-36, 2014).
PMID- 29947902
TI - Sensitive electrochemical detection of sodium azide based on the electrocatalytic
activity of the pasting liquid of a carbon paste electrode.
AB - Sodium azide (NaN3) is highly toxic and widely used in, for example, automobile
airbags and biochemical laboratories. The electrochemical detection of sodium
azide on commonly used electrodes is challenging due to sluggish electron
transfer, but it has been achieved using a boron-doped diamond thin-film
electrode and a highly oriented pyrolytic graphite electrode. Utilizing the
electrocatalytic activity of the pasting liquid of a carbon paste electrode, we
developed an effective method for the electrochemical detection of sodium azide
in which silicone oil was employed as the pasting liquid of the carbon paste
electrode. This simple and cheap silicone-oil-based carbon paste electrode
exhibited comparable sensitivity to the boron-doped diamond thin-film electrode
and highly oriented pyrolytic graphite electrode. The limit of detection for
sodium azide at the silicone-oil-based carbon paste electrode was found to be 0.1
MUM. Recoveries from diluted human serum samples were between 97.2 and 101.3%.
Graphical abstract ?.
PMID- 29947903
TI - Dispersive liquid-liquid microextraction as a new clean-up procedure for the
determination of parabens, perfluorinated compounds, UV filters, biocides,
surfactants, and plasticizers in root vegetables.
AB - An analytical method based on ultrasound-assisted extraction and dispersive
liquid-liquid microextraction (DLLME) clean-up has been developed and validated
for the determination of 31 emerging pollutants in root vegetables. The target
compounds were four preservatives, six perfluoroalkyl compounds, six UV filters,
two biocides, eight anionic surfactants, three nonionic surfactants, and two
plasticizers. The type and volume of the extraction solvent, those of the
disperser solvent, the pH and NaCl content of the DLLME aqueous phase, the amount
of sample, and the sonication time were optimized. Box-Behnken experimental
design was applied to select the best extraction conditions. Matrix-matched
calibration curves were used for quantification. Four internal standards were
used to compensate for residual matrix effects. Good linearity (R2 > 0.990),
accuracies (expressed as the relative recovery) of >82%, and precisions
(expressed as the relative standard deviation) of <18% were achieved. Method
quantification limits (MQLs), calculated from spiked samples as the
concentrations corresponding to signal-to-noise ratios of 10, were in the range
0.1-25 ng g-1 dry weight (d.w.). MQL values for 26 of the 31 target compounds
were lower than 5 ng g-1 d.w. The method was successfully applied to determine
the target pollutants in carrots, potatoes, and turnips from a local market. To
the best of our knowledge, the proposed method constitutes the first application
of DLLME as a clean-up procedure for the multiresidue determination of emerging
pollutants in vegetables. The method affords similar recoveries and method
detection limits to previously reported methods but requires smaller solvent
volumes and sample amounts and is less expensive.
PMID- 29947904
TI - Rapid characterization of cocaine in illicit drug samples by 1D and 2D NMR
spectroscopy.
AB - Seized samples of illegally produced cocaine have a very large variability in
composition; a fact that may result in a challenge to their analysis. We
demonstrate here a simple and fast method to detect the presence of cocaine in
both hydrochloride and free-base forms in illicit drug samples by nuclear
magnetic resonance (NMR) spectroscopy. This is achieved by combining the commonly
used 1D spectra and diffusion-ordered spectroscopy and introducing the 2D maximum
quantum NMR approach to forensic analysis. The protocol allows the facile
determination of the cocaine forms even in the presence of multiple adulterants.
By relying on non-uniform sampling acceleration of 2D spectroscopy, the
identification can be obtained in less than 3 min for 10 mg of product. Moreover,
we show that intermolecular interactions of the sample constituents, while
affecting the analysis result, do not interfere with the quality of the detection
of the proposed protocol.
PMID- 29947905
TI - Toward continuous amperometric gas sensing in ionic liquids: rationalization of
signal drift nature and calibration methods.
AB - Sensor signal drift is the key issue for the reliability of continuous gas
sensors. In this paper, we characterized the sensing signal drift of an
amperometric ionic liquid (IL)-based oxygen sensor to identify the key chemical
parameters that contribute to the signal drift. The signal drifts due to the
sensing reactions of the analyte oxygen at the electrode/electrolyte interface at
a fixed potential and the mass transport of the reactant and product at the
electrode/electrolyte interface were systematically studied. Results show that
the analyte concentration variation and the platinum electrode surface activity
are major factors contributing to sensing signal drift. An amperometric method
with a double potential step incorporating a conditioning step was tested and
demonstrated to be useful in reducing the sensing signal drift and extending the
sensor operation lifetime. Also, a mathematic method was tested to calibrate the
baseline drift and sensing signal sensitivity change for continuous sensing. This
study provides the understanding of the chemical processes that contribute to the
IL electrochemical gas (IL-EG) sensor signal stability and demonstrates some
effective strategies for signal drift calibration that can increase the
reliability of the continuous amperometric sensing. Graphical Abstract ?.
PMID- 29947906
TI - Active learning materials for teaching electrochemistry.
PMID- 29947907
TI - Elucidation of chromatographic peak shifts in complex samples using a
chemometrical approach.
AB - Chromatographic retention time peak shifts between consecutive analyses is a well
known fact yet not fully understood. Algorithms have been developed to align
peaks between runs, but with no specific studies considering the causes of peak
shifts. Here, designed experiments reveal chromatographic shift patterns for a
complex peptide mixture that are attributable to the temperature and pH of the
mobile phase. These results demonstrate that peak shifts are highly structured
and are to a high degree explained by underlying differences in physico-chemical
parameters of the chromatographic system and also provide experimental support
for the alignment algorithm called the generalized fuzzy Hough transform which
exploits this fact. It can be expected that the development of alignment
algorithms enters a new phase resulting in increasingly accurate alignment by
considering the latent structure of the peak shifts.
PMID- 29947908
TI - Cardiovascular effects of cisapride and prucalopride on human 5-HT4 receptors in
transgenic mice.
AB - Cisapride and prucalopride act as 5-HT4 receptor agonists. As a part of our
ongoing effort to study the utility of a transgenic (TG) mouse model
overexpressing cardiac 5-HT4 receptors, we assessed the extent to which we could
recapitulate cisapride and prucalopride agonists. Contractile studies were
performed using isolated left and right atrial preparations of TG mice showing
cardiac-specific human 5-HT4a receptor expression and those of their wild-type
(WT) littermates. 5-Hydroxytryptamine (5-HT), cisapride, and prucalopride exerted
concentration-dependent positive inotropic effects in the left atrial
preparations of TG mice. Moreover, 5-HT induced concentration-dependent
arrhythmias in the right atrial preparations of TG mice starting from 10-nM
concentration. However, cisapride induced arrhythmias not only in the right
atrial preparations of TG mice but also in the right atrial preparations of WT
mice. For instance, 10 MUM cisapride induced arrhythmias in the right atrial
preparations of TG and WT mice to the same extent. Prucalopride did not exert
concentration-dependent proarrhythmic effects in the isolated atrial preparations
(left or right, WT or TG). Furthermore, cisapride and prucalopride increased the
contractility and beating rate in vivo in TG mice, as assessed by performing
echocardiography and surface electrocardiography. In summary, our results
indicate that cisapride and prucalopride increase contractility and beating rate
in the isolated atrial preparations of TG mice or in intact TG mice. Moreover, 5
HT induced arrhythmias in the isolated right atrial preparations of TG mice in a
concentration-dependent manner. Furthermore, cisapride induced arrhythmias in the
isolated right atrial preparations of both TG and WT mice. In contrast,
prucalopride did not induce arrhythmias in the atrial preparations (left or
right) of both WT and TG mice. We suggest that the present TG mouse model might
be useful to predict at least some important cardiac effects of 5-HT4 receptor
agonists in the human heart.
PMID- 29947910
TI - Trace Element Concentrations in European Pond Turtles (Emys orbicularis) from
Brenne Natural Park, France.
AB - We assessed trace elements concentration in European pond turtle (Emys
orbicularis) from Brenne Natural Park (France). We sampled road-killed turtles (N
= 46) to measure the concentrations of 4 non-essential (Ag, Cd, Hg, and Pb) and
10 essential (As, Co, Cr, Cu, Fe, Mn, Ni, Se, V, and Zn) elements in muscle,
skin, liver and claws. Body size or sex did not influence the concentrations of
most elements; except for Hg (liver, skin and claws) and Zn (muscle) which
increased with body size. We found relatively high concentrations of Hg and Zn,
possibly linked to fish farming. This result deserves future investigations to
evaluate possible ecotoxicological effects on E. orbicularis.
PMID- 29947909
TI - Ellagic acid prevents dementia through modulation of PI3-kinase-endothelial
nitric oxide synthase signalling in streptozotocin-treated rats.
AB - Ellagic acid (EGA)-enriched dietary supplements are widely acclaimed, owing to
its versatile bioactivities. Previously, we reported that chronic administration
of EGA prevented the impairment of cognitive abilities in rats using the
intracerebroventricular-administered streptozotocin (STZ-ICV) model of
Alzheimer's disease. Impairment of phosphoinositide 3 (PI3)-kinase-regulated
endothelial nitric oxide synthase (eNOS) activity by central administration of
STZ in rodents instigates dementia. The aim of the present study was to delineate
the role of PI3-kinase-eNOS activity in the prevention of STZ-ICV-induced memory
dysfunctions by EGA. The Morris water maze and elevated plus maze tests were
conducted, and brain oxidative stress markers (TBARS, GSH, SOD, CAT), nitrite,
acetylcholinesterase (AChE), LDH, TNF-alpha and eNOS were quantified.
Administration of EGA (35 mg/k, p.o.) for 4 weeks daily attenuated the STZ-ICV (3
mg/kg)-triggered increase of brain oxidative stress, nitrite and TNF-alpha
levels; AChE and LDH activity; and decline of brain eNOS activity. The memory
restoration by EGA in STZ-ICV-treated rats was conspicuously impaired by N(G)
nitro-L-arginine methyl ester (L-NAME) (20 mg/kg, 28 days) and wortmannin (5
MUg/rat; ICV) treatments. Wortmannin (PI3-kinase inhibitor) and L-NAME groups
manifested elevated brain oxidative stress, TNF-alpha content and AChE and LDH
activity and diminished nitrite content. L-NAME (arginine-based competitive eNOS
inhibitor) enhanced the eNOS expression (not activity) whereas wortmannin reduced
the brain eNOS levels in EGA- and STZ-ICV-treated rats. However, the L-NAME group
exhibited superior cognitive abilities in comparison to the wortmannin group. It
can be concluded that EGA averted the memory deficits by precluding the STZ-ICV
induced loss of PI3-kinase-eNOS signalling in the brain of rats.
PMID- 29947911
TI - Heavy Metal Pollution and Ecological Risk Assessment of the Agriculture Soil in
Xunyang Mining Area, Shaanxi Province, Northwestern China.
AB - Mining is considered to be one of the most significant sources of environmental
pollution with regard to heavy metals. Mineral mining causes large quantities of
mercury, cadmium, and other elements to be released into the environment and
naturally poses a serious threat to environment. This paper will analyze the
pollution status of agricultural soil caused by the mining of heavy metals in
various mining areas in the Xunyang County in the Shaanxi Province of China, an
area in famous for its resource mining. Equally, it will look at the potential
ecological risk assessment process that is used to analyze the ecological risks
of mining heavy metals in agricultural soil located in the surrounding areas.
Based on the soil investigation, As pose a moderate ecological risk on the Au
mining area. In addition, the Hg metals pose a significantly high potential
ecological risk and Cd metals pose a considerable potential ecological risk on
the Hg mining area. In the Pb-Zn mining area, a significantly high potential
ecological risk was mainly posed by Cd. These results suggest that many heavy
metals pose a high potential ecological risk on the agricultural soil in these
three mining areas in the Xunyang County, and may cause elevated heavy metal
contents in crops, eventually jeopardizing the health of local residents who
consume food grown in polluted soil.
PMID- 29947912
TI - Determination of 226Ra Contamination Depth Around Phosphogypsum Pit Using In-Situ
Gamma Spectrometer.
AB - The feasibility of applying multiple photopeak method (MPM) and peak to valley
ratio (PVRM) method to determine Radium-226 contamination depth (226Ra hc) has
been investigated. Gamma spectra in eight positions around phosphogypsum disposal
pit has been measured using portable NaI(Tl) gamma spectrometer. MPM was
investigated by calculating the ratio [Formula: see text] of 609 keV gamma line
net counts to the corresponding value of 352 keV. PVRM was investigated by
calculating the ratio [Formula: see text] of net counts of 609 keV gamma line to
the corresponding valley counts. 226Ra hc in the positions has been determined
using traditional soil coring. It was found that, [Formula: see text] and
[Formula: see text] have good linear correlations with 226Ra hcTherefore, 226Ra
hc can be determined by MPM and PVRM. These methods save a lot of time, costs and
efforts in comparison with the traditional one.
PMID- 29947913
TI - Decay of Quinclorac in Acidic Paddy Soil and Risk Evaluation to the Subsequent
Crop, Tobacco (Nicotiana tabacum L.).
AB - Quinclorac is a selective herbicide commonly used in China to control
monocotyledonous weeds in paddy fields. A field experiment was conducted to
quantify the environmental behavior of quinclorac in acidic paddy soil under rice
(Oryza sativa L.) field conditions, and to evaluate the risk of its residues to
the subsequent crop of tobacco (Nicotiana tabacum L.). Rice was sprayed once with
quinclorac 50% WP at 562.5, 375.0, or 187.5 g a.i. ha-1 at 7 days after
transplanting the seedlings. Decay of quinclorac in paddy field soil followed
first-order kinetics, with a half-life of 28.29-30.27 days. At harvest time,
0.090, 0.074 and 0.034 mg kg-1 of quinclorac were found in soils following the
above-described treatments, respectively. Leaves of the subsequent crop, tobacco,
sown the year after the quinclorac treatments, exhibited different dose-dependent
degrees of visible phytotoxicity symptoms.
PMID- 29947914
TI - Impacts of a Compound Amendment on Cd Immobilization, Enzyme Activities and Crop
Uptake in Acidic Cd-Contaminated Paddy Soils.
AB - This study assessed the effectiveness of limestone-montmorillonite-rapeseed
residue-Si fertilizer compound amendment on the bioavailability and crop uptake
of cadmium (Cd) and enzyme activities in acidic paddy soils. Applying the
compound amendment at ratios of 1%-3% increased soil pH by 0.1-1.9 units,
decreased leaching ratios of soil Cd 4.0%-22%, and decreased exchangeable and
carbonated Cd 42%-55% and 27%-49%, respectively. Organic matter-bound Cd
increased 47%-62% (p < 0.05). Cadmium concentrations decreased in the roots,
culms, leaves, and grains of rice grown in the Cd-contaminated soils by 37%-81%,
18%-73%, 29%-64% and 27%-63%, respectively, (p < 0.05). Catalase and urease
activities increased 2.5%-63% and 3.9%-36%, (p < 0.05), respectively. Applying
this compound amendment may significantly mitigate soil acidification and
decrease the bioavailability and crop uptake of Cd in acidic Cd-contaminated
paddy soils.
PMID- 29947915
TI - Age-related differences in alcohol attention bias: a cross-sectional study.
AB - INTRODUCTION: Addiction models theorise that alcohol attention bias (AAB) for
alcohol-related cues develops through a process of classical conditioning and
that attentional processes shift from controlled to automatically modulated
responses. At the point of automaticity, alcohol cues grab the attention of
problem drinkers beyond conscious control and can trigger alcohol use. To fully
understand this shift, AAB should be thought of as developing on a continuum from
when alcohol use commences. Despite this, little is known about AAB differences
in younger populations who are at an early stage in their exposure to alcohol and
related cues. RATIONALE: This study compared AAB for alcohol cues across age
groups (early adolescent, late adolescent, and young adult) and drinking groups
(heavy drinkers, light drinkers, and non-drinkers) to provide a cross-sectional
examination of differences in AAB and their relationship to alcohol use and age.
METHODS: Eye tracking was employed to measure several elements of attentional
processing during exposure to alcohol cues. Differences across age groups and
drinking groups were examined. RESULTS: Differences in controlled attention were
found between heavy and light drinkers. As age increases, a shift towards
automaticity can be seen with alcohol-related cues attracting the attention of
young adult drinkers earlier in stimulus presentation. CONCLUSIONS: This cross
sectional approach provides an insight into AAB across a key developmental
period. It highlights that influential processes underpinning AAB may change and
how rapidly it may approach automaticity. The implications of these findings are
discussed.
PMID- 29947916
TI - The effects of a combination of intravenous dexamethasone and ketamine on
postoperative mood in patients undergoing laparoscopically assisted-gynecologic
surgery.
AB - BACKGROUND: It has been known that anesthetic adjuvants such as dexamethasone or
ketamine might change mood. This study aimed to investigate the effects of a
single dose of each drug individually along with their combined usage on
postoperative mood changes in patients undergoing gynecologic surgery. METHODS:
Two hundred ninety-seven patients randomly allocated were divided into three
groups. Group K (n = 99) received a single dose of ketamine (0.5 mg/kg iv); group
D (n = 99) received a single dose of dexamethasone (0.1 mg/kg iv), and group KD
(n = 99) received both ketamine (0.5 mg/kg iv) and dexamethasone (0.1 mg/kg iv)
at 5 min after the induction of anesthesia. A change in the patient health
questionnaire (PHQ)-9 scores on the first and third day after surgery, the
duration of anesthesia, the postoperative visual analog scale (VAS) for pain, and
the patient controlled analgesia (PCA) consumption were evaluated. RESULTS:
Groups K and KD showed a significant reduction in PHQ-9 score on both the first
and third day after surgery compared with those recorded preoperatively and in
group D (P < 0.01). There were no differences in the group D PHQ-9 scores pre-
and post-operatively. The VAS for pain 24 h after surgery and the PCA consumption
in group KD decreased significantly compared to the other two groups (P < 0.05).
CONCLUSIONS: A single dose of ketamine (0.5 mg/kg) with or without combination
with dexamethasone (0.1 mg/kg) give iv 5 min after induction of general
anesthetic produced significant improvement in the postoperative mood scores. A
single intravenous dose of dexamethasone (0.1 mg/kg) alone did not change
postoperative mood scores. The VAS for pain 24 h after surgery and the PCA
consumption was significantly lower in patients who received combination of both
drugs.
PMID- 29947917
TI - Compulsive sucrose- and cocaine-seeking behaviors in male and female Wistar rats.
AB - RATIONALE: Compulsive cocaine use is a key feature of cocaine addiction and
understanding the factors that promote the development of such a behavior will
provide important insights into the mechanism of cocaine addiction and is
essential for the clinical management of the disorder. OBJECTIVES: This study
aimed to determine how the preexisting compulsive reward-seeking behavior is
related to the development of compulsive cocaine-seeking behavior in male and
female rats and the potential impact of the reward value and estrous cycle on
such behaviors. METHODS: Adult male and female Wistar rats were first trained to
self-administer sucrose pellets under a chained schedule, and then, the intensity
response effects of footshock punishment on sucrose SA reinforced by different
values of sucrose were measured. Subsequently, the same rats went on to self
administer intravenous cocaine and the punishment intensity-response effects on
cocaine SA reinforced by different doses of cocaine were similarly determined.
For the female rats, the measurements were made during different phases of the
estrous cycle. RESULTS: The rats showed a wide range of levels of the compulsive
behaviors despite the similar training history. Surprisingly, the compulsive
sucrose-seeking behavior did not predict the compulsive cocaine-seeking behavior
in either sex. Increasing cocaine dose significantly increased the compulsive
cocaine-seeking behavior in the female but not male rats. Estrous cycle did not
have impact on the compulsive behaviors. CONCLUSION: Preexisting differences in
compulsive sucrose-seeking behavior do not predict compulsive cocaine-seeking
behavior. Compulsive cocaine-seeking behavior is influenced by cocaine dose but
not estrous cycle in the female rats.
PMID- 29947918
TI - [Bariatric surgery: Expectations and therapeutic goals-a contradiction?]
AB - In the majority of patients with morbid obesity, metabolic/bariatric surgery
leads to relevant and sustained weight loss and improves obesity-related
comorbidities, quality of life and functionality. Moreover, the associated
reduction of risk factors for cardiovascular events and cancerous diseases has
been shown to improve life expectations. Due to its excellent antidiabetic
effect, the currently valid national S3 guidelines now recommend
metabolic/bariatric surgery in patients who have a body mass index (BMI) >=30
kg/m2 with poorly controlled diabetes. The Edmonton staging system enables a
multidimensional consideration of the severity grade of obesity for each
individual patient independent of the BMI. Patients with relevant obesity-related
metabolic comorbidities should be prioritized for treatment and if possible
before the occurrence of end-organ damage that is at least in some cases
irreversible and which also increases the perioperative risk. Therapeutic goals
for each individual patient should be carefully defined preoperatively in order
to mediate realistic expectations. Unrealistic expectations, such as "surgery
solves my problems", "surgery makes me more beautiful", "surgery eliminates
stigma", and "surgery guarantees success", are common in bariatric surgery
patients. These unrealistic expectations can lead to frustration and to severe
psychological decompensation and need to be addressed as early as possible by an
interdisciplinary team. Redundancies, conclusive and empathic communication in
the team improve therapy adherence, the expectations and therefore the overall
outcome.
PMID- 29947919
TI - [Evaluation of the infrastructure for clinical surgical studies in Germany : A
nationwide survey of the surgical study network CHIR-Net].
AB - BACKGROUND: In order to improve the quality and quantity of clinical trials in
Germany a surgical study network called CHIR-Net funded by the Federal Ministry
of Education and Research (BMBF) was established. The focus was on building an
infrastructure for the performance of surgical multicenter, randomized controlled
clinical trials with the inclusion of university and non-university hospitals.
The education of clinicians with an interest in clinical research and the
transfer of research ideas (as investigator initiated trials, IIT) were clear
goals for this grant. The aim of this article is to evaluate the incentive
measures by comparison of clinics with and without participation in CHIR-Net
structures. MATERIAL AND METHODS: A nationwide online survey included a total of
475 heads of surgical departments of whom 268 worked in hospitals with
participation in CHIR-Net structures and 207 at hospitals without. They were
asked to answer 20 questions in the following categories: education and
activities in clinical trials, number of publications and participation in grant
applications at the BMBF and/or German Research Foundation (DFG). The evaluation
of the survey was performed according to a priori defined criteria. RESULTS: The
response rate was 23.4% and 68 CHIR-Net hospitals and 43 non-CHIR-Net hospitals
participated in the survey. The comparison of the results between the hospitals
showed that the network significantly contributed to improvement of the study
culture, especially in the areas of education in clinical research,
infrastructure for clinical trials, study activity, grant applications and
publication rates. CONCLUSION: The hospitals that participate in CHIR-Net
structures were superior to hospitals that do not participate in CHIR-Net
structures regarding study activity, infrastructure for clinical trials, study
specific education of clinicians, grant applications and publication rates. The
goal of the grant was achieved and the funding led to manifold, long-term
cooperation and a clear improvement of the study culture in surgery.
PMID- 29947920
TI - [Perioperative safety of intraperitoneal aerosol chemotherapy : Analysis of our
first 111 pressurized intraperitoneal aerosol chemotherapy (PIPAC) procedures].
AB - BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new
tool in the treatment of patients with peritoneal carcinomatosis. The aerosol
containing chemotherapeutic drugs is administered laparoscopically into the
abdominal cavity to achieve a local treatment effect. This can be carried out in
combination with systemic chemotherapy. MATERIAL AND METHODS: Within the
framework of a register study, we prospectively documented and evaluated the data
of our first 111 PIPAC procedures. The analysis focused on perioperative patient
safety and safety at the workplace. Perioperative clinical patient data were
analyzed and the platinum concentration in the operating room was checked by wipe
samples. RESULTS: A total of 62 patients were scheduled for PIPAC and 121
operations were carried out. In 9 procedures a secure access to the abdomen could
not be found and 54 patients received 111 PIPAC treatments. One patient died as a
result of intestinal perforation, six bowel lesions were treated immediately and
healed without further complications. A further patient developed a postoperative
renal failure. Otherwise, there was no major complications and no cases of
toxicity. CONCLUSION: The PIPAC procedure can be used as a supplement to systemic
drug treatment for peritoneal carcinomatosis. An exact selection of suitable
patients is important. The PIPAC is a low-risk procedure when performed under
strict inclusion criteria and under standardized conditions, for the patients and
also the surgical staff.
PMID- 29947921
TI - Association between diabetes distress and all-cause mortality in Japanese
individuals with type 2 diabetes: a prospective cohort study (Diabetes Distress
and Care Registry in Tenri [DDCRT 18]).
AB - AIMS/HYPOTHESIS: The absence of data on the direct association between diabetes
specific distress and all-cause mortality in individuals with diabetes prompted
us to examine the temporal association between Problem Areas in Diabetes (PAID)
survey scores and the subsequent risk of all-cause mortality in a cohort of
individuals with type 2 diabetes. METHODS: Longitudinal data from 3305
individuals with diabetes were obtained from a large Japanese diabetes registry.
Independent correlations between quintiles of PAID total scores or PAID scores of
>=40 and all-cause mortality (median follow-up of 6.1 years) were examined using
Cox proportional hazards models with adjustment for potential confounders.
RESULTS: The study population included 1280 women and 2025 men with a mean age of
64.9 years, BMI of 24.6 kg/m2 and HbA1c level of 58.7 mmol/mol (7.5%). In the
multivariable-adjusted model, compared with the first quintile of PAID scores,
the multivariable-adjusted HRs (95% CIs) for all-cause mortality for the second
to fifth quintiles were 1.11 (0.77, 1.60; p = 0.56), 0.87 (0.56, 1.35; p =
0.524), 0.95 (0.63, 1.46; p = 0.802) and 1.60 (1.09, 2.36; p = 0.016),
respectively. Compared with a PAID score of <40, the multivariable-adjusted HR
for all-cause mortality of those with a score of >=10 was 1.56 (95% CI 1.17,
2.08; p = 0.002). In subgroup analyses, the association between PAID score and
all-cause mortality was found in men (HR 1.76; 95% CI 1.26, 2.46) but not in
women (HR 1.09; 95% CI 0.60, 2.00), with a significant interaction between
diabetes distress and sex (p = 0.0336). CONCLUSIONS/INTERPRETATION: We observed a
significant positive association between high diabetes distress and all-cause
mortality in men with diabetes.
PMID- 29947922
TI - Novel approaches to restore beta cell function in prediabetes and type 2
diabetes.
AB - The World Health Organization estimates that diabetes prevalence has risen from
108 million in 1980 to 422 million in 2014, with type 2 diabetes accounting for
more than 90% of these cases. Furthermore, the prevalence of prediabetes
(impaired fasting glucose and/or impaired glucose tolerance) is more than 40% in
some countries and is associated with a global rise in obesity. Therefore it is
imperative that we develop new approaches to reduce the development of
prediabetes and progression to type 2 diabetes. In this review, we explore the
gains made over the past decade by focused efforts to improve insulin secretion
by the beta cell or insulin sensitivity of target tissues. We also describe
multitasking candidates, which could improve both beta cell dysfunction and
peripheral insulin sensitivity. Moreover, we highlight provocative findings
indicating that additional glucose regulatory tissues, such as the brain, may be
key therapeutic targets. Taken together, the promise of these new multi-faceted
approaches reinforces the importance of understanding and tackling type 2
diabetes pathogenesis from a multi-tissue perspective.
PMID- 29947923
TI - Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722
women in two independent populations.
AB - AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a common complication of
pregnancy that has substantial short- and long-term adverse health implications
for women and their children. However, large-scale studies on genetic risk loci
for GDM remain sparse. METHODS: We conducted a case-control study among 2636
women with GDM and 6086 non-GDM control women from the Nurses' Health Study II
and the Danish National Birth Cohort. A total of 112 susceptibility genetic
variants confirmed by genome-wide association studies for type 2 diabetes were
selected and measured. A weighted genetic risk score (GRS) was created based on
variants that were significantly associated with risk of GDM after correcting for
the false discovery rate. RESULTS: For the first time, we identified eight
variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3),
rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2),
rs11787792 (GPSM1) and rs7041847 (GLIS3). In addition, we confirmed three
variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs4506565 (TCF7L2), that
had previously been significantly associated with GDM risk. Furthermore, compared
with participants in the first (lowest) quartile of weighted GRS based on these
11 SNPs, the ORs for GDM were 1.07 (95% CI 0.93, 1.22), 1.23 (95% CI 1.07, 1.41)
and 1.53 (95% CI 1.34, 1.74) for participants in the second, third and fourth
(highest) quartiles, respectively. The significant positive associations between
the weighted GRS and risk of GDM persisted across most of the strata of major
risk factors for GDM, including family history of type 2 diabetes, smoking
status, BMI and age. CONCLUSIONS/INTERPRETATION: In this large-scale case-control
study with women from two independent populations, eight novel GDM SNPs were
identified. These findings offer the potential to improve our understanding of
the aetiology of GDM, and particularly of biological mechanisms related to beta
cell function.
PMID- 29947924
TI - Caveolar targeting links Kv1.3 with the insulin-dependent adipocyte physiology.
AB - The voltage-dependent potassium channel Kv1.3 participates in peripheral insulin
sensitivity. Genetic ablation of Kv1.3 triggers resistance to diet-induced weight
gain, thereby pointing to this protein as a pharmacological target for obesity
and associated type II diabetes. However, this role is under intense debate
because Kv1.3 expression in adipose tissue raises controversy. We demonstrated
that Kv1.3 is expressed in white adipose tissue from humans and rodents.
Moreover, other channels, such as Kv1.1, Kv1.2, Kv1.4 and especially Kv1.5, from
the same Shaker family are also present. Although elevated insulin levels and
adipogenesis remodel the Kv phenotype, which could lead to multiple heteromeric
complexes, Kv1.3 markedly participates in the insulin-dependent regulation of
glucose uptake in mature adipocytes. Adipocyte differentiation increased the
expression of Kv1.3, which is targeted to caveolae by molecular interactions with
caveolin 1. Using a caveolin 1-deficient 3T3-L1 adipocyte cell line, we
demonstrated that the localization of Kv1.3 in caveolar raft structures is
important for proper insulin signaling. Insulin-dependent phosphorylation of the
channel occurs at the onset of insulin-mediated signaling. However, when Kv1.3
was spatially outside of these lipid microdomains, impaired phosphorylation was
exhibited. Our data shed light on the putative role of Kv1.3 in weight gain and
insulin-dependent responses contributing to knowledge about adipocyte physiology.
PMID- 29947925
TI - Targeting Nrf-2 is a promising intervention approach for the prevention of
ethanol-induced liver disease.
AB - Alcoholic liver disease (ALD) remains to be a worldwide health problem. It is
generally accepted that oxidative stress plays critical roles in the pathogenesis
of ALD, and antioxidant therapy represents a logical strategy for the prevention
and treatment of ALD. Nuclear factor erythroid-derived 2-like 2 (NFE2L2 or Nrf-2)
is essential for the antioxidant responsive element (ARE)-mediated induction of
endogenous antioxidant enzymes such as heme oxygenase 1 (HO-1) and glutamate
cysteine ligase [GCL, the rate-limiting enzyme in the synthesis of glutathione
(GSH)]. Activation of Nrf-2 pathway by genetic manipulation or pharmacological
agents has been demonstrated to provide protection against ALD, which suggests
that targeting Nrf-2 may be a promising approach for the prevention and treatment
of ALD. Herein, we review the relevant literature about the potential
hepatoprotective roles of Nrf-2 activation against ALD.
PMID- 29947926
TI - OSBP-related protein-2 (ORP2): a novel Akt effector that controls cellular energy
metabolism.
AB - ORP2 is a ubiquitously expressed OSBP-related protein previously implicated in
endoplasmic reticulum (ER)-lipid droplet (LD) contacts, triacylglycerol (TG)
metabolism, cholesterol transport, adrenocortical steroidogenesis, and actin
dependent cell dynamics. Here, we characterize the role of ORP2 in carbohydrate
and lipid metabolism by employing ORP2-knockout (KO) hepatoma cells (HuH7)
generated by CRISPR-Cas9 gene editing. The ORP2-KO and control HuH7 cells were
subjected to RNA sequencing, analyses of Akt signaling, carbohydrate and TG
metabolism, the extracellular acidification rate, and the lipidome, as well as to
transmission electron microscopy. The loss of ORP2 resulted in a marked reduction
of active phosphorylated Akt(Ser473) and its target Glycogen synthase kinase
3beta(Ser9), consistent with defective Akt signaling. ORP2 was found to form a
physical complex with the key controllers of Akt activity, Cdc37, and Hsp90, and
to co-localize with Cdc37 and active Akt(Ser473) at lamellipodial plasma membrane
regions, in addition to the previously reported ER-LD localization. ORP2-KO
reduced glucose uptake, glycogen synthesis, glycolysis, mRNA-encoding glycolytic
enzymes, and SREBP-1 target gene expression, and led to defective TG synthesis
and storage. ORP2-KO did not reduce but rather increased ER-LD contacts under
basal culture conditions and interfered with their expansion upon fatty acid
loading. Together with our recently published work (Kentala et al. in FASEB J
32:1281-1295, 2018), this study identifies ORP2 as a new regulatory nexus of Akt
signaling, cellular energy metabolism, actin cytoskeletal function, cell
migration, and proliferation.
PMID- 29947929
TI - Mobile stroke unit use for prehospital stroke treatment-an update.
AB - BACKGROUND: Acute ischemic stroke is a treatable disease. Moreover, there is
increasing evidence supporting mechanical recanalization for large-vessel
occlusion, even beyond a strict time window. However, only small numbers of
patients receive causal treatment. METHODS: One of the main reasons that patients
do not receive causal therapy is their late arrival at the correct target
hospital, which, depending on the type of stroke, is either a regional stroke
unit or a comprehensive stroke center for interventional treatment. In order to
triage patients correctly, a fast and complex diagnostic work-up is necessary,
allowing a stroke specialist to decide on the best therapy option. As treatment
possibilities become more comprehensive with the need for individualized
decisions, the gap between treatment options and practical implementation is
increasing. RESULTS: The "mobile stroke unit" concept encompasses the
administration of prehospital acute stroke diagnostic work-up, therapy
initiation, and triage to the correct hospital using a specially equipped
ambulance, staffed with a team specialized in stroke. The concept, which was
conceived and first put into practice in Homburg/Saar, Germany, in 2008, is
currently spreading with more than 20 active mobile stroke unit centers
worldwide. The use of mobile stroke units can reduce the time until stroke
treatment by 50% with a tenfold increase of patients treated within the first 60
min of symptom onset. CONCLUSION: The mobile stroke unit concept for acute stroke
prehospital management is spreading worldwide. Intensive research is still needed
to analyze the best setting for prehospital stroke management.
PMID- 29947930
TI - [Clinical target volume : Principles and limits].
AB - BACKGROUND: The clinical target volume (CTV) is regarded fundamental for
radiotherapy planning by the International Commission on Radiation Units and
Measurements (ICRU). OBJECTIVES: The aim of this article is to give an overview
on the basics and problems of defining the CTV for radiotherapy planning.
MATERIALS AND METHODS: After briefly defining CTV, a short description of the
process to homogenize CTV in intraindividual comparisons is given, where special
attention is paid to radiological requirements. This information is summarized in
a number of tables. RESULTS: CTV is the most complex volume among the target
volumes that have been defined by the ICRU. A survey of the determinants of the
definition of CTV is given. CONCLUSIONS: This overview on the basic rules of how
to define CTVs can help to increase the understanding of the radiological
requirements for optimum imaging to support radiotherapy planning regardless of
the specialty of the physician.
PMID- 29947928
TI - Coordination of microtubule acetylation and the actin cytoskeleton by formins.
AB - The acetylation of the lysine 40 residue of alpha-tubulin was described more than
30 years ago and has been the subject of intense research ever since. Although
the exact function of this covalent modification of tubulin in the cell remains
unknown, it has been established that tubulin acetylation confers resilience to
mechanical stress on the microtubules. Formins have a dual role in the fate of
the actin and tubulin cytoskeletons. On the one hand, they catalyze the formation
of actin filaments, and on the other, they bind microtubules, act on their
stability, and regulate their acetylation and alignment with actin fibers. Recent
evidence indicates that formins coordinate the actin cytoskeleton and tubulin
acetylation by modulating the levels of free globular actin (G-actin). G-actin,
in turn, controls the activity of the myocardin-related transcription factor
serum response factor transcriptional complex that regulates the expression of
the alpha-tubulin acetyltransferase 1 (alpha-TAT1) gene, which encodes the main
enzyme responsible for tubulin acetylation. The effect of formins on tubulin
acetylation is the combined result of their ability to activate alpha-TAT1 gene
transcription and of their capacity to regulate microtubule stabilization. The
contribution of these two mechanisms in different formins is discussed,
particularly with respect to INF2, a formin that is mutated in hereditary human
renal and neurodegenerative disorders.
PMID- 29947927
TI - Mechanisms of protein toxicity in neurodegenerative diseases.
AB - Protein toxicity can be defined as all the pathological changes that ensue from
accumulation, mis-localization, and/or multimerization of disease-specific
proteins. Most neurodegenerative diseases manifest protein toxicity as one of
their key pathogenic mechanisms, the details of which remain unclear. By
systematically deconstructing the nature of toxic proteins, we aim to elucidate
and illuminate some of the key mechanisms of protein toxicity from which
therapeutic insights may be drawn. In this review, we focus specifically on
protein toxicity from the point of view of various cellular compartments such as
the nucleus and the mitochondria. We also discuss the cell-to-cell propagation of
toxic disease proteins that complicates the mechanistic understanding of the
disease progression as well as the spatiotemporal point at which to
therapeutically intervene. Finally, we discuss selective neuronal vulnerability,
which still remains largely enigmatic.
PMID- 29947931
TI - Imaging and the completion of the omics paradigm in breast cancer.
AB - Within the field of oncology, "omics" strategies-genomics, transcriptomics,
proteomics, metabolomics-have many potential applications and may significantly
improve our understanding of the underlying processes of cancer development and
progression. Omics strategies aim to develop meaningful imaging biomarkers for
breast cancer (BC) by rapid assessment of large datasets with different
biological information. In BC the paradigm of omics technologies has always
favored the integration of multiple layers of omics data to achieve a complete
portrait of BC. Advances in medical imaging technologies, image analysis, and the
development of high-throughput methods that can extract and correlate multiple
imaging parameters with "omics" data have ushered in a new direction in medical
research. Radiogenomics is a novel omics strategy that aims to correlate imaging
characteristics (i. e., the imaging phenotype) with underlying gene expression
patterns, gene mutations, and other genome-related characteristics. Radiogenomics
not only represents the evolution in the radiology-pathology correlation from the
anatomical-histological level to the molecular level, but it is also a pivotal
step in the omics paradigm in BC in order to fully characterize BC. Armed with
modern analytical software tools, radiogenomics leads to new discoveries of
quantitative and qualitative imaging biomarkers that offer hitherto unprecedented
insights into the complex tumor biology and facilitate a deeper understanding of
cancer development and progression. The field of radiogenomics in breast cancer
is rapidly evolving, and results from previous studies are encouraging. It can be
expected that radiogenomics will play an important role in the future and has the
potential to revolutionize the diagnosis, treatment, and prognosis of BC
patients. This article aims to give an overview of breast radiogenomics, its
current role, future applications, and challenges.
PMID- 29947932
TI - [Gross tumor volume (GTV) : Basics, methods, registration, limitations].
AB - CLINICAL ISSUE: Gross tumor volume (GTV) denotes the macroscopic tumor which as
the central target volume needs to be correctly identified for successful
radiotherapy. STANDARD RADIOLOGICAL METHODS AND METHODICAL INNOVATIONS: In
precision radiotherapy, GTV is outlined on 3D tomographic images. The basis is
computed tomography (CT), which is often supplemented by additional diagnostic
information, e. g. magnetic resonance imaging (MRI) and positron emission
tomography (PET). New developments like dual-energy CT, functional MRI and
specific PET tracers facilitate a continuously better differentiation between
tumor and surrounding normal tissue. ACHIEVEMENTS: The concept of GTV is a
central part of radiotherapy and the basis of radiation treatment planning.
Studies regarding the interobserver variability are performed in order to analyze
the impact of different imaging modalities, interventions and observer
qualifications, and to deduce steps to constantly improve the practical
realization. Each tumor entity presents specific challenges which are
demonstrated here using examples.
PMID- 29947933
TI - [Imaging of side effects after radiation therapy].
AB - BACKGROUND: Peritumoral normal tissue is inevitably also irradiated during
radiotherapy, depending on the location and size of the target volume as well as
the cumulative dose. Depending on the temporal course after irradiation acute,
subacute, and chronic alterations are described in co-irradiated normal tissue
that can be detected by imaging. Radiation damage can be transient or persistent.
OBJECTIVE: This article gives an overview of the most important signs of
radiation-induced radiogenic alterations to tissue in various organ systems.
FINDINGS: Frequent radiation-induced tissue alterations found by imaging are
pneumonitis, disturbance of the blood-brain barrier, radionecrosis of brain
tissue, radiogenic liver damage, mucositis, colitis, osteitis, osteoradionecrosis
and myositis. The combination with systemic chemotherapy or immunotherapy can
increase the severity of radiogenic reactions of normal tissue. RECOMMENDATIONS
FOR AFTERCARE: The most important differential diagnosis for radiogenic
alterations to normal tissue is post-therapeutic tumor recurrence. Besides
typical latency periods, location and matching with the radiation field are
important differentiation criteria, depending on the tumor biology and the
radiation technique. The follow-up schedule should follow the current guidelines
and the clinical condition of the patient should be additionally considered. The
radiologist needs to be familiar with the typical imaging morphology of
radiogenic tissue changes to avoid false interpretation during follow-up
investigations.
PMID- 29947934
TI - [Imaging of abdominal tumors in childhood and adolescence : Part II: relevant
intra-abdominal and retroperitoneal tumor entities].
AB - Abdominal and pelvic tumors in children and adolescents can be manifested intra
abdominally and also often in the retroperitoneum. The most important pediatric
primary retroperitoneal space-occupying lesions are nephroblastoma (Wilms' tumor)
and neuroblastoma, whereby imaging plays a decisive role in the diagnostics and
differentiation of the two entities. Benign tumors of the mesentery and
gastrointestinal tract occur more frequently in children than malignant lesions.
The benign entities include lipoma, polyps and vascular tumors, such as lymphatic
malformations. Of the malignant sarcomas, abdominal rhabdomyosarcomas (RMS) occur
relatively often in childhood and adolescence. The most frequent pediatric
abdominal lymphoma is Burkitt's lymphoma, an aggressive subtype of non-Hodgkin's
lymphoma. Relevant tumor entities in childhood are also germ cell tumors, which
originate from the genitals (gonadal) or can be extragonadally manifested. The
benignancy or malignancy of germ cell tumors ranges from benign teratomas to
highly malignant entities, such as yolk sac tumors. The germ cell tumors, just as
all pediatric abdominal mass lesions, show a broad spectrum of tumor
aggressiveness, malignancy and therefore also prognosis and mortality for the
affected children and adolescents.
PMID- 29947935
TI - [CNS manifestations of neurocutaneous syndromes].
AB - CLINICAL/METHODICAL ISSUE: Phakomatoses refer to a heterogeneous and
inconsistently defined group of neurocutaneous disorders. Tuberous sclerosis,
neurofibromatosis types 1 and 2, Sturge-Weber syndrome and von Hippel-Lindau
disease are entities with typical findings in neuroimaging studies STANDARD
RADIOLOGICAL METHODS: These findings are usually easily depicted on magnetic
resonance imaging (MRI) studies, thus, making diagnosis easier.
PMID- 29947936
TI - [Treatment of chronic migraine with botulinum neurotoxin A : Expert
recommendations of the German Migraine and Headache Society].
AB - BACKGROUND: Injection of botulinum neurotoxin A (BoNT-A) according to the PREEMPT
(Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) paradigm has been
approved for the treatment of refractory chronic migraine in Germany in 2011.
OBJECTIVE: The practical application raises some questions, such as the choice of
dose and injection intervals during the course of the treatment, and the
appropriate time point for discontinuation of BoNT-A treatment. MATERIAL AND
METHODS: Taking into account the existing literature, the German Migraine and
Headache Society (Deutsche Migrane- und Kopfschmerzgesellschaft, DMKG) gives
recommendations for the treatment of chronic migraine with BoNT-A. RESULTS:
Treatment is usually started with a dose of 155 U BoNT-A. During the first year
of treatment, 3-month injection intervals are recommended. Goal of the treatment
is an improvement of migraine by >=30%. If needed, dose escalation up to 195 U
can be used to reach this goal. If improvement by >=30% is not reached after the
third injection cycle, the treatment is usually considered to be insufficiently
efficient and discontinuation is recommended. If a stable success is reached
during the first year of treatment, prolongation of injection intervals to 4
months can be considered. If success continues to be stable for at least two 4
month intervals, discontinuation of BoNT-A treatment can be tried. CONCLUSION:
The literature on these points is insufficient for recommendations at the
guideline level. The present recommendations are based on an expert consensus of
the DMKG for the structured approach to the treatment of chronic migraine with
BoNT-A.
PMID- 29947937
TI - [Resilience to mental disorders in old age].
AB - BACKGROUND: Why does the aspect of aging justify a special survey of resilience
to the development of mental disorders? Patterns of chronic stress burden change
with age (e. g. disappearance of workplace-related stress, but increased risk of
frequent chronic diseases). Moreover, capabilities and cognitive strategies of
stress coping differ between young and older adults. MATERIAL AND METHODS: The
article summarizes relevant age aspects of resilience to mental disorders and
evaluates the current knowledge concerning consecutive development of prevention
strategies for avoidance of affective disorders and dementia. RESULTS AND
DISCUSSION: Stress-aggravating reduced cognitive functioning (especially
executive problem solving) can be observed together with, probably stress
reducing, age-specific appraisal preferences (positivity effect) in older
persons. Other age-specific aspects are resilience mechanisms against cognitive
decline and dementia development despite cerebrovascular and neurodegenerative
brain pathology-related conditions, which are referred to as cognitive reserve.
Different cognitive reserve enhancing strategies can effectively contribute to
dementia prevention.
PMID- 29947939
TI - [Chinese medicine and constructivism-a new way in psychotherapy].
AB - BACKGROUND: The background of this study is twofold: basic methodological
differences between Western Biomedicine and Classical Chinese Medicine (CCM) and
obvious parallels between the methodology of psychotherapy and CCM. OBJECTIVES:
Drawing on available investigations on the methodology of CCM, the analysis of
structural parallels between CCM and Western psychotherapy tries to enrich the
methodological self-conception of psychotherapy in order to provide impulses for
the new approaches to psychotherapeutic practice. METHODS: The reciprocal
interpretation of CCM about the patient's state draws on a language of metaphors.
These metaphors "mediate" between the various positions of the universal
interdependency and the human being, who is able to understand the language. The
constructive realistic methodology in general and the epistemological method of
"alienation" in particular, provide an instrument for the decodification of these
metaphors. RESULTS: In the context of CCM, the process dynamics of mental healing
are based on hermeneutical principals. Every operation carried out by the CCM
therapist is not organ medical in nature but a purely semantic form. These
semantic operations aim to provide a meaningful integration of problematical
behavior (in terms of meaning) into metaphorically logical structures in order to
stimulate a coherent self-understanding of the suffering individual, which is
associated with healing effects. In this context, it is crucial for CCM that
there is no conceptual division between body and soul with respect to the
therapy. This enables a completely different comprehensive treatment of mental
problems than biomedicine is able to offer, due to its methodological
presuppositions.
PMID- 29947940
TI - [First description of Schilder's disease : Paul Ferdinand Schilder and his
struggle for the delimitation of a new entity].
AB - Paul Ferdinand Schilder was born in Vienna in 1886 and died in New York in 1940.
He is nowadays remembered predominantly for his contributions to modern
psychiatry and psychotherapy; however, he was also a neurologist and
neuroscientist and in particular in his early years, he researched and published
on neuropathological topics. This paper focuses on his scientific work during his
years in Middle Germany (1909-1914), where he worked with Gabriel Anton in Halle
and Paul Flechsig in Leipzig. During those years, he laid the foundations for his
definition, clinical classification and differentiation of encephalitis
periaxialis diffusa. Today, this inflammatory brain disease is known as
Schilder's disease and is of some importance as a rare differential diagnosis of
multiple sclerosis (MS), especially in children. Schilder's reflections and
findings were based on his scrupulous and detailed analysis of only a few medical
histories, which also comprised histological neuropathological examinations, as
well as on his extensive and critical review of the relevant literature of the
time. His aim was to differentiate encephalitis periaxialis diffusa from brain
tumors, MS and Heubner's diffuse sclerosis. Schilder's scientific achievement,
made in relatively young years, is still impressive even to the present day due
do its thoroughness and accuracy as well as the enormous workload and ambition it
required. Even though ambitious, Schilder was always prepared to critically
review his own ideas.
PMID- 29947938
TI - [Imaging in acute ischemic stroke using automated postprocessing algorithms].
AB - There are several automated analytical methods to detect thromboembolic vascular
occlusions, the infarct core and the potential infarct-endangered tissue (tissue
at risk) by means of multimodal computed tomography (CT) and magnetic resonance
imaging (MRI). The infarct core is more reliably visualized by diffusion-weighted
imaging (DWI) MRI or CT perfusion than by native CT. The extent of tissue at risk
and endangerment can only be estimated; however, it seems essential whether
"tissue at risk" actually exists. To ensure consistent patient care, uniform
imaging protocols should be acquired in the referring hospital and thrombectomy
center and the collected data should be standardized and automatically evaluated
and presented. Whether patients with a large infarct core and with or without
tissue at risk or patients with large vessel occlusion (LVO) but low NIHSS
benefit from thrombectomy has to be evaluated in controlled clinical trials using
standardized imaging protocols. A promising, potentially time-saving approach is
also native CT and CT angiography using a flat-panel detector angiography system
for assessment of vessel occlusion and leptomeningeal collaterals.
PMID- 29947941
TI - Verification of bleeding points in carotid blowout syndrome using guidewire
manipulation.
AB - PURPOSE: Carotid blowout syndrome (CBS) is a catastrophic complication of
aggressive treatment of head and neck cancer. Early detection of bleeding points
with embolization is a life-saving procedure; however, some bleeding points may
be difficult to identify. Our aim was to determine whether guidewire manipulation
(GWM) could be used to verify bleeding point locations in patients with CBS.
METHODS: Of the 92 patients with CBS referred for embolization in a 5-year
period, 14 men and one woman (mean age 58 years) had bleeding points at locations
that could not be definitely determined. We used GWM to verify the presence of
these bleeding points. We assessed the anatomy of the ruptured arteries,
technical details of GWM, and the angiographic and clinical outcomes. RESULTS:
Bleeding points were difficult to detect because of the presence of small
arterial pouches (n = 6) or multiple small arterial pouches (n = 9) in the
unilateral or bilateral carotid arteries. Bleeding point locations were
accurately identified using GWM in the internal carotid artery (n = 7), carotid
bulb (n = 4), or common carotid artery (n = 4). Balloon-assisted GWM was applied
in one patient. Fiber coils (n = 15) and/or liquid adhesives (n = 2) were used to
occlude the affected artery. Endovascular management was technically successful
in all patients and resulted in immediate cessation of hemorrhage without
recurrence in a mean 22-month clinical follow-up. CONCLUSION: GWM is a simple and
effective method for verifying bleeding points in ruptured arteries and
preventing erroneous occlusion by embolization.
PMID- 29947942
TI - What is the role of vertebral augmentation for osteoporotic fractures? A review
of the recent literature.
AB - PURPOSE: Vertebral augmentation procedures such as vertebroplasty and kyphoplasty
are utilized in the treatment of vertebral compression fractures (VCFs). However,
their capacity for providing analgesia, reducing disability, and improving
quality of life in patients with osteoporotic VCFs remains a topic of debate. The
objective of this narrative review is to summarize the latest evidence for the
safety and efficacy of vertebral augmentation for osteoporotic vertebral
compression fractures (VCFs). METHODS: A systematic literature search was
conducted using the PubMed and Cochrane electronic databases for systematic
reviews, review articles, meta-analyses, and randomized clinical trials prior to
May 2017. The keywords were "vertebroplasty," "kyphoplasty," and "vertebral
augmentation." RESULTS: Thirty-three papers (7 systematic reviews, 6 cohort
studies, 15 randomized clinical trials, and 5 international guidelines) were
included in this narrative review. CONCLUSION: Vertebral augmentation is a safe
procedure, with low rates of serious complications and no increase in subsequent
post-treatment fracture risk.
PMID- 29947943
TI - Identification and annotation of bovine granzyme genes reveals a novel granzyme
encoded within the trypsin-like locus.
AB - Granzymes are a family of serine proteases found in the lytic granules of
cytotoxic T lymphocytes and natural killer (NK) cells, which are involved in
killing of susceptible target cells. Most information on granzymes and their
enzymatic specificities derive from studies in humans and mice. Although
granzymes shared by both species show a high level of conservation, the
complement of granzyme genes differs between the species. The aim of this study
was to identify granzyme genes expressed in cattle, determine their genomic
locations and analyse their sequences to predict likely functional specificities.
Orthologues of the five granzyme genes found in humans (A, B, H, K and M) were
identified, as well a novel gene designated granzyme O, most closely related to
granzyme A. An orthologue of granzyme O was found in pigs and a non-function
version was detected in the human genome. Use of specific PCRs demonstrated that
all of these genes, including granzyme O, are expressed in activated subsets of
bovine lymphocytes, with particularly high levels in CD8 T cells. Consistent with
findings in humans and mice, the granzyme-encoding genes were located on three
distinct genomic loci, which correspond to different proteolytic enzymatic
activities, namely trypsin-like, chymotrypsin-like and metase-like. Analysis of
amino acid sequences indicated that the granzyme proteins have broadly similar
enzymatic specificities to their human and murine counterparts but indicated that
granzyme B has a different secondary specificity. These findings provide the
basis for further work to examine their role in the cytotoxic activity of bovine
CD8 T cells.
PMID- 29947944
TI - Two class I genes of the chicken MHC have different functions: BF1 is recognized
by NK cells while BF2 is recognized by CTLs.
AB - The function of the chicken's major histocompatibility complex (MHC or B complex)
class I major (BF2) and minor (BF1) glycoproteins is compared for their
expression, ability to present viral antigens to cytotoxic T lymphocytes (CTLs),
and interaction with natural killer (NK) cells. MHC-restricted CTLs recognized
virus antigen in the context of the BF2*21 major glycoprotein but not the BF1*21
minor glycoprotein. Marek's disease virus (MDV), a large DNA virus known to
reduce the cell surface expression of class I glycoprotein, reduced the
expression of BF2 glycoprotein while BF1glycoprotein expressions are remained as
no change or slight increase. In addition, the expression of BF1*21 class I
glycoprotein protected target cells from NK cell lysis while the expression of
the BF2*21 class I glycoprotein enhanced NK cell lysis of target cells.
Therefore, BF1 and BF2 provide two different cellular immune functions; BF1
negatively regulates the NK cell killing activity and BF2 restricts the antigen
specific CTL immune response.
PMID- 29947946
TI - Evolutionary Dynamics of Copy Number and Meiotic Recombination in Murine 5S rDNA:
Possible Involvement of Natural Selection.
AB - We investigated evolutionary trends of the 5S ribosomal RNA gene in the house
mouse, Mus musculus. First, we assessed the 5S cluster and copy numbers in eight
laboratory strains by pulsed-field gel electrophoresis. The copy numbers in seven
lines were estimated to be around 130-170 copies per cluster, with 63 copies in
the remaining strain, implying that the copy number can change drastically and
has been maintained under certain evolutionary constraints at ~ 140 copies.
Second, we addressed the frequency of meiotic recombination mediated by the 5S
cluster by performing a mating experiment with laboratory strains, and found that
the 5S cluster did not accelerate recombination events. Third, we surveyed
recombination events of the 5S-containing chromosome region in wild mice from the
Japanese Islands, where the two subspecies lineages, M. m. castaneus and M. m.
musculus, are historically mingled, and found that the influence of the 5S
cluster on meiotic recombination was limited. Finally, we examined the nucleotide
diversity of six genes in the neighboring regions of the 5S cluster and found
reduced genetic diversity in the regions on both sides of the cluster, suggesting
the involvement of either positive or background selection in the population
level sequence similarity of the 5S clusters. Therefore, the mouse 5S genes are
considered to be evolving toward sequence similarity within a given cluster by
certain intrachromosomal mechanisms and toward sharing of a specific 5S cluster
within a population by certain selective processes.
PMID- 29947947
TI - Invasion probabilities, hitting times, and some fluctuation theory for the
stochastic logistic process.
AB - We consider excursions for a class of stochastic processes describing a
population of discrete individuals experiencing density-limited growth, such that
the population has a finite carrying capacity and behaves qualitatively like the
classical logistic model Verhulst (Corresp Math Phys 10:113-121, 1838) when the
carrying capacity is large. Being discrete and stochastic, however, our
population nonetheless goes extinct in finite time. We present results concerning
the maximum of the population prior to extinction in the large population limit,
from which we obtain establishment probabilities and upper bounds for the
process, as well as estimates for the waiting time to establishment and
extinction. As a consequence, we show that conditional upon establishment, the
stochastic logistic process will with high probability greatly exceed carrying
capacity an arbitrary number of times prior to extinction.
PMID- 29947948
TI - [Tips and tricks in court-Practical experience from a medical viewpoint].
AB - When it comes to legal aspects and doctors have to go to court, most likely they
will serve as an expert or regular witness or as a defendant in a civil
litigation in case of recourse claims and only rarely as defendants in a criminal
case. With the exception of expert testimonies by seasoned physicians, this is
not usually an easy situation. This article addresses important aspects of the
preparation for a trial and its procedures. If appropriately prepared, and if
necessary represented by a good attorney, these sometimes emotionally stressful
situations can be mastered quite well.
PMID- 29947949
TI - [Interpretation of tuberculosis and hepatitis screening before immunosuppressive
treatment].
AB - An unrecognized latent tuberculosis infection (LTBI) may be reactivated under
immunosuppressive therapy and become life threatening. Diagnosing LTBI requires
the combination of targeted patient history and physical examination with the
results of an interferon-gamma release assay (IGRA) and in addition, a chest X
ray is needed to rule out active tuberculosis. Established therapies for LTBI
reduce the reactivation risk by approximately 80%. For the initial screening of
an HBV infection HBsAg and anti-HBc are determined. Hereby, HBsAg carriers (high
HBV reactivation risk, indications for antiviral prophylaxis) and serologically
resolved HBV infections (low HBV reactivation risk, use of prophylaxis only in
high-risk immunosuppression) can be reliably detected. A previously unrecognized
HCV infection, with an increased risk of developing liver cirrhosis during
immunosuppression, can be detected in screening by anti-HCV antibodies and be
successfully treated with antivirals without interferon.
PMID- 29947950
TI - Effects of CYP2D6 and CYP3A5 genetic polymorphisms on steady-state
pharmacokinetics and hemodynamic effects of tamsulosin in humans.
AB - PURPOSE: Tamsulosin is one of the most potent drugs currently available to treat
benign prostatic hyperplasia. Cytochrome P450 (CYP) 2D6 and CYP3A are the two
major enzymes responsible for tamsulosin metabolism. The purpose of this study
was to evaluate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on the
pharmacokinetics and hemodynamic effects of tamsulosin in humans. METHODS: Twenty
nine male subjects were enrolled and their CYP2D6 (*2,*4,*5,*10,*14,*21,*41, and
*xN) and CYP3A5 (*5) genotypes were screened. Tamsulosin was administered daily
for 6 days to assess its steady-state pharmacokinetics and hemodynamic effects
according to CYP2D6 and CYP3A5 genotypes. RESULTS: CYP2D6 group 3 (with genotype
*10/*10 or *5/*10) exhibited higher plasma levels than CYP2D6 group 1 (with
genotype *1/*1,*1/*2,*1/*2xN, or *2/*10xN) or CYP2D6 group 2 (with genotype
*1/*10,*1/*41, or *2/*5) (trough concentrations for groups 1, 2, and 3: 1.3, 1.8,
and 3.8 ng/mL, respectively [P < 0.001]; peak concentrations for groups 1, 2, 3:
8.3, 10.0, and 13.8 ng/mL, respectively [P < 0.005]). Similarly, CYP2D6 genotypes
influenced the hemodynamic effects of tamsulosin based on systolic and diastolic
blood pressures. However, the CYP3A5*3 polymorphism did not affect tamsulosin
plasma levels and its hemodynamic effects. CONCLUSION: The CYP2D6 but not the
CYP3A5 genetic polymorphisms affected the pharmacokinetics and the hemodynamic
effects of tamsulosin.
PMID- 29947951
TI - AtARRE, an E3 ubiquitin ligase, negatively regulates ABA signaling in Arabidopsis
thaliana.
AB - KEY MESSAGE: The RING-type E3 ligase AtARRE participates in the plant ABA
responding as a negative regulator. Ubiquitination protease system (UPS) is
significant in post-transcriptional regulation. In UPS, E3 ligase recognizes the
substrate protein and mediates the polyubiquitin chain onto the substrate. Here,
we identified a new gene, named Arabidopsis thaliana ABA-related RING-type E3
ligase (AtARRE), which induced by ABA and NaCl. AtARRE encodes a functional RING
type E3 ligase protein localized in nucleus and plasma membrane of Arabidopsis.
Physiological analysis demonstrated that mutation of AtARRE (T-DNA insert mutants
atarre-1 and atarre-2) caused plants hypersensitivity to ABA, including enhanced
stomatal closure, reduced root elongation and seed germination. However,
overexpression of AtARRE transgenic lines caused plants hyposensitive to ABA
compared with WT and mutant atarre plants. Under the treatment of ABA, the
transcript abundances of ABA-responsive genes RD29A, RD29B, RD22 and ABI5 in
atarre mutant plants were markedly higher than those of WT and AtARRE
overexpression lines. Hence, these results indicate that AtARRE acts as a
negative regulator of ABA-mediated stress responses in Arabidopsis.
PMID- 29947952
TI - TaMIR1139: a wheat miRNA responsive to Pi-starvation, acts a critical mediator in
modulating plant tolerance to Pi deprivation.
AB - KEY MESSAGE: Wheat miRNA member TaMIR1139 targets genes functional in various
families and plays crucial roles in regulating plant Pi starvation tolerance.
Through regulating target genes at posttranscriptional or translational level,
plant miRNAs are involved in mediating diverse biological processes associated
with growth, development, and responses to adverse stresses. In this study, we
characterized the expression pattern and function of TaMIR1139, a miRNA member of
wheat (T. aestivum) under Pi deprivation. TaMIR1139 precursor is also present in
N. tabucum, suggesting the conserved nature of miR1139 across monocots and
eudicots. TaMIR1139 targets seven genes within different families. The
transcripts abundance of TaMIR1139 was induced upon Pi deprivation and the
upregulated expression under Pi starvation was downregulated by the Pi recovery
treatment, In contrast, the genes targeted by TaMIR1139 exhibited reduced
transcripts upon Pi starvation and their downregulated expression was recovered
by Pi-recovery condition, suggesting the regulation of them under TaMIR1139
through a cleavage mechanism. TaMIR1139 overexpression conferred the Pi-deprived
plants improved phenotype, biomass, photosynthesis, and Pi acquisition.
Transcriptome analysis identified numerous genes involving biological process,
cellular components, and molecular function were differentially expressed in the
TaMIR1139 overexpression lines, which suggests the TaMIR1139-mediated plant Pi
starvation tolerance to be associated with the role of miRNA in extensively
modulating the transcript profiling. A phosphate transporter (PT) gene NtPT
showed significantly upregulated expression in TaMIR1139 overexpression lines;
overexpression of it conferred plants improved Pi acquisition upon Pi starvation,
suggesting its contribution to the TaMIR1139-mediated plant low-Pi stress
resistance. Our investigation indicates that TaMIR1139 is critical in plant Pi
starvation tolerance through transcriptionally regulating the target genes and
modulating the Pi stress-defensiveness processes.
PMID- 29947953
TI - Expression of both Arabidopsis gamma-tubulin genes is essential for development
of a functional syncytium induced by Heterodera schachtii.
AB - KEY MESSAGE: After initial up-regulation, expression of TUBG1 and TUBG2 is
significantly down-regulated in mature syncytia, but lack of expression of either
of gamma-tubulin genes reduces numbers of nematode infections and developing
females. Infective second stage juveniles of sedentary plant parasitic nematode
Heterodera schachtii invade the root vascular tissue and induce a feeding site,
named syncytium, formed as a result of cell hypertrophy and partial cell wall
dissolution leading to a multinucleate state. Syncytium formation and maintenance
involves a molecular interplay between the plant host and the developing
juveniles leading to rearrangements and fragmentation of the plant cytoskeleton.
In this study, we investigated the role of two Arabidopsis gamma-tubulin genes
(TUBG1 and TUBG2), involved in MTs nucleation during syncytium development.
Expression analysis revealed that both gamma-tubulin's transcript levels changed
during syncytium development and after initial up-regulation (1-3 dpi) they were
significantly down-regulated in 7, 10 and 15 dpi syncytia. Moreover, TUBG1 and
TUBG2 showed distinct immunolocalization patterns in uninfected roots and
syncytia. Although no severe changes in syncytium anatomy and ultrastructure in
tubg1-1 and tubg2-1 mutants were observed compared to syncytia induced in wild
type plants, nematode infection assays revealed reduced numbers of infecting
juveniles and developed female nematodes in mutant lines. Our results indicate
that the expression of both TUBG1 and TUBG2 genes, although generally down
regulated in mature syncytia, is essential for successful root infection,
development of functional syncytium and nematode maturation.
PMID- 29947954
TI - Identification of a seed maturation protein gene from Coffea arabica (CaSMP) and
analysis of its promoter activity in tomato.
AB - KEY MESSAGE: A seed maturation protein gene (CaSMP) from Coffea arabica is
expressed in the endosperm of yellow/green fruits. The CaSMP promoter drives
reporter expression in the seeds of immature tomato fruits. In this report, an
expressed sequence tag-based approach was used to identify a seed-specific
candidate gene for promoter isolation in Coffea arabica. The tissue-specific
expression of the cognate gene (CaSMP), which encodes a yet uncharacterized
coffee seed maturation protein, was validated by RT-qPCR. Additional expression
analysis during coffee fruit development revealed higher levels of CaSMP
transcript accumulation in the yellow/green phenological stage. Moreover, CaSMP
was preferentially expressed in the endosperm and was down-regulated during water
imbibition of the seeds. The presence of regulatory cis-elements known to be
involved in seed- and endosperm-specific expression was observed in the CaSMP 5'
upstream region amplified by genome walking (GW). Additional histochemical
analysis of transgenic tomato (cv. Micro-Tom) lines harboring the GW-amplified
fragment (~ 1.4 kb) fused to uidA reporter gene confirmed promoter activity in
the ovule of immature tomato fruits, while no activity was observed in the seeds
of ripening fruits and in the other organs/tissues examined. These results
indicate that the CaSMP promoter can be used to drive transgene expression in
coffee beans and tomato seeds, thus representing a promising biotechnological
tool.
PMID- 29947955
TI - The effect of aging and contextual information on manual asymmetry in tool use.
AB - Healthy aging affects manual asymmetries in simple motor tasks, such as
unilateral reaching and aiming. The effects of aging on manual asymmetries in the
performance of a complex, naturalistic task are unknown, but are relevant for
investigating the praxis system. This study examined how aging influences manual
asymmetry in different contexts in a tool manipulation task. Fifty healthy, right
hand-dominant young (N = 29; 21.41 +/- 2.87 years), and elderly (N = 21; mean:
74.14 +/- 6.64 years) participants performed a 'slicing' gesture in response to a
verbal command in two contexts: with (tool) and without the tool (pantomime). For
interjoint relationships between shoulder plane of elevation and elbow flexion, a
HAND * AGE * CONTEXT interaction existed (F1,43 = 4.746, p = 0.035). In
pantomime, interjoint control deviated more in the left (non-dominant) than the
right (dominant) limb in the elderly adult group (Wilcoxon, p = 0.010). No such
differences existed in the young adult group (Wilcoxon, p = 0.471). Furthermore,
contextual information reduced interjoint deviation in young adults when the task
was performed with the right (dominant) hand (Wilcoxon, p = 0.001) and in the
elderly adults when the task was performed with the left (non-dominant) hand
(Wilcoxon, p = 0.012). The presence of the tool did not reduce interjoint
deviation for the right hand in the elderly group (Wilcoxon, p = 0.064) or the
left hand in the young group (Wilcoxon, p = 0.044). Deviation within trials
(i.e., intrasubject deviation) in elbow flexion was higher in the elderly
relative to the young adult group (p = 0.003). Finally, resultant peak velocities
were smaller (p = 0.002) and cycle duration longer (p < 0.0001) in the elderly
adult group. This study provides novel evidence that aging affects manual
asymmetries and sensorimotor control in a naturalistic task and warrants that
aging research considers the context in which the task is performed.
PMID- 29947956
TI - Bimanual joint action: correlated timing or "bimanual" movements accomplished by
two people.
AB - A crew of two rowing together in perfect synchrony is an example of a task that
requires each performer to maintain meticulous timing when coordinating their
movements with the other. At the individual level, temporal coordination of the
limbs has been observed in bimanual pointing movements even when made to targets
of different distance. Timing of the arms is not independent; rather there is a
natural temporal coupling. The aim of this experiment was to investigate whether
the temporal characteristics of pointing movements can be observed under joint
conditions. Sixteen pairs of participants made short and long, unimanual and
bimanual pointing movements. In the unimanual and bimanual solo conditions,
participants made the movements alone. In the joint condition, each participant
contributed one arm to the joint "bimanual" movements. Absolute temporal coupling
at movement initiation and termination was measured by the differences in
reaction time and total response time. Relative temporal coupling at movement
initiation and termination was measured by correlating reaction time and total
response time of the left and right limbs. Pointing movements had synchronous
movement termination in the bimanual solo conditions and asynchronous termination
in the unimanual solo and bimanual joint conditions. The initiation and
termination of the arms were not correlated in the unimanual solo condition
(initiation r = 0.01, termination r = 0.03). Small-to-medium correlations (r =
0.19, r = 0.24) were observed in the bimanual joint condition, and they were
larger than the unimanual solo condition (p = 0.022, p = 0.063). As expected,
there were large correlations in the bimanual solo conditions (r = 0.91, r =
0.81). Our findings suggest that absolute temporal coupling does not occur
between individuals, but there is evidence for relative temporal coupling in the
bimanual joint condition.
PMID- 29947957
TI - Disturbances of spatial reference frame and postural asymmetry after a chronic
stroke.
AB - Asymmetrical postural behaviors are frequently observed after a stroke. They are
due in part to the sensorimotor deficit, but they could also be related to a
disorder of the representation of the body in space. The objective was to
determine whether the asymmetrical postural behaviors of chronic stroke patients
are related with a disruption of the perception of spatial frame. 30 chronic
stroke patients (mean age 60.3 year +/- 10, mean delay post-stroke 4.78 year +/-
3), 15 patients with right brain damage (RBD) and 15 patients with left brain
damage (LBD), and 20 healthy subjects participated in the study. Postural
asymmetry was detected by the evaluation of body weight repartition on a force
platform (weight body asymmetry) and was related to the longitudinal body axis
(LBA) and the subjective straight ahead (SSA) (egocentric space representation)
and to the subjective visual vertical (SVV) (allocentric space representation) by
a multivariate analysis of variance adjusted with motor function and sensitivity
as covariables. Both patients with RBD (35% +/- 8) and LBD (39% +/- 4) had body
weight asymmetry and there was still space misperception at this stage of
recovery, especially in the RBD group. WBA was related to LBA when considering
both patients with RBD and LBD (p = 0.03). However, this relation was dependent
on the side of the lesion (p = 0.0006) with a stronger relation in the RBD group
(0.01). No relation with WBA was found neither with SSA (p = 0.58) nor with SVV
(p = 0.47). This study pointed out a strong relationship between disturbance in
the perception of the longitudinal body axis and postural asymmetry in chronic
strokes, and especially within the RBD group. Conversely, no other spatial
perturbations seemed to be involved in this particular postural behavior.
PMID- 29947958
TI - Effect of a cognitive task on online adjustments when avoiding stepping on an
obstacle and stepping on a target during walking in young adults.
AB - During locomotion, we respond to environmental and task changes by adjusting
steps length and width. Different protocols involving stepping on targets and
obstacle avoidance suggest the involvement of cortical and subcortical pathways
in these online adjustments. The addition of a concomitant cognitive task (CT)
can affect these online corrections depending on the neural pathway used.
Thereby, we investigated the online adjustment using a target stepping task and a
planar obstacle avoidance task in young adults and analyzed the effect of a CT on
these adjustments. Twenty young adults executed two blocks of trials of walking
performing the target task (TT) and obstacle avoidance task (OAT), with and
without a concomitant CT. In the TT, participants stepped on a target projected
on the ground, whereas in the OAT they avoided stepping on an obstacle projected
on the ground. The target/obstacle could change its original position in four
directions at contralateral foot contact on the ground. Overall, the CT did not
affect the latency to start the adjustments due to target/obstacle change. The
main changes were restricted to the frontal plane adjustments. The latency for
the medial and lateral choices in the OAT was ~ 200 ms, whereas for the TT was ~
150 ms. These results suggest the involvement of a slow cortical pathway in the
OAT in the frontal plane modifications. In turn, the TT may be controlled by one
of two fast adjustment neural pathways.
PMID- 29947959
TI - Shared variance of oculomotor phenotypes in a large sample of healthy young men.
AB - This study used canonical correlation analysis to investigate patterns of shared
variance between parameters measured in seven different occulomotor function
tasks, namely the visually guided saccade task, the antisaccade task, the closed
loop smooth-pursuit task, the open-loop smooth-pursuit task, and three active
visual fixation tasks. These tasks were performed by 2130 young army recruits.
Only a small percentage (1-10%) of shared variance existed between sets of
parameters for all oculomotor function tasks measured. The most correlated tasks
were the visually guided saccade and the antisaccade. The first common factor
correlated with speed of performance between these tasks (latency), while the
second and third correlated with accuracy of performance. Better performance in
active visual fixation tasks correlated with better performance accuracy (lower
error rate) and increased speed (lower latency) in the antisaccade and saccade
tasks as well as better performance in the closed-loop smooth-pursuit task
(increase in gain and decrease in the rate of unwanted saccades during pursuit).
Better performance in the closed-loop smooth-pursuit task (increased gain and
decreased number of unwanted saccades) also correlated with increased accuracy
and increased speed of performing saccades and antisaccades. Finally, the open
loop fixation task had no correlation with all other oculomotor tasks except for
a very weak negative correlation with the closed-loop pursuit task where better
performance (increased gain) in one correlated with worse performance (decreased
gain) in the other. The results of this analysis showed that a small percentage
of variance is shared among different oculomotor function tasks. The structure of
this shared variance could be used to derive common oculomotor function indices
to study their relation to genetic and other sources of inter-subject variation.
PMID- 29947960
TI - Blood cell count indexes as predictors of outcomes in advanced non-small-cell
lung cancer patients treated with Nivolumab.
AB - Lung cancer is the most common malignancy worldwide. Despite significant advances
in diagnosis and treatment, mortality rates remain extremely high, close to
incidence rates. Several targeted therapies have been recently introduced for the
treatment of non-small cell lung cancer (NSCLC), the most common type of lung
cancer. Nivolumab, a monoclonal antibody that targets programmed death-1 (PD-1),
was the first immune checkpoint inhibitor approved for the treatment of patients
with advanced/metastatic NSCLC not responding to platinum-based chemotherapy.
Biomarkers predicting response to these therapies would allow early
identification of non-responders and timely implementation of appropriate
combination strategies, avoiding inadequate and expensive therapies. The role of
the neutrophil to lymphocyte ratio and other blood cell count indexes as possible
biomarkers of response has been recently investigated. We discuss the encouraging
results reported on the topic, provide new data from our personal experience, and
discuss opportunities for further research.
PMID- 29947961
TI - Fighting breast cancer stem cells through the immune-targeting of the xCT cystine
glutamate antiporter.
AB - Tumor relapse and metastatic spreading act as major hindrances to achieve
complete cure of breast cancer. Evidence suggests that cancer stem cells (CSC)
would function as a reservoir for the local and distant recurrence of the
disease, due to their resistance to radio- and chemotherapy and their ability to
regenerate the tumor. Therefore, the identification of appropriate molecular
targets expressed by CSC may be critical in the development of more effective
therapies. Our studies focused on the identification of mammary CSC antigens and
on the development of CSC-targeting vaccines. We compared the transcriptional
profile of CSC-enriched tumorspheres from an Her2+ breast cancer cell line with
that of the more differentiated parental cells. Among the molecules strongly
upregulated in tumorspheres we selected the transmembrane amino-acid antiporter
xCT. In this review, we summarize the results we obtained with different xCT
targeting vaccines. We show that, despite xCT being a self-antigen, vaccination
was able to induce a humoral immune response that delayed primary tumor growth
and strongly impaired pulmonary metastasis formation in mice challenged with
tumorsphere-derived cells. Moreover, immunotargeting of xCT was able to increase
CSC chemosensitivity to doxorubicin, suggesting that it may act as an adjuvant to
chemotherapy. In conclusion, our approach based on the comparison of the
transcriptome of tumorspheres and parental cells allowed us to identify a novel
CSC-related target and to develop preclinical therapeutic approaches able to
impact on CSC biology, and therefore, hampering tumor growth and dissemination.
PMID- 29947962
TI - Using the inbred mouse strain SPRET/EiJ to provide novel insights in inflammation
and infection research.
AB - Inbred mouse strains derived from the species Mus spretus have been very
informative in the study of certain gene polymorphisms in inflammation and
infection. Based on our interest in sepsis, we used SPRET/EiJ mice and mapped
several critical loci that are linked to sensitivity to cytokine-induced
inflammation and endotoxemia. These studies were based on prominent phenotypes
that have never been observed in strains derived from Mus musculus and we mapped
them at a resolution that enables us to draw conclusions on the mechanisms. Now
that the genome of SPRET/EiJ has been sequenced, and other tools have become
available, it is time to revisit this strain and emphasize its advantages and
disadvantages as a research tool and a discovery platform.
PMID- 29947963
TI - The impact of host genetic background in the Pseudomonas aeruginosa respiratory
infections.
AB - Understanding the significance of human genetic diversity in modulating host
susceptibility to opportunistic infections is an emerging challenge in the field
of respiratory illnesses. While it is recognized that diverse bacterial strains
account for differential disease manifestations, emerging data indicate that host
genetic diversity is an important determinant factor that influences the severity
of opportunistic infections. With particular regard to respiratory illnesses
mediated by the gram-negative bacterium Pseudomonas aeruginosa, diverse genetic
background is also emerging as a key contributor. Human-genome-wide association
studies are a common approach for determining the inter-individual genetic
variation associated with variability of the pulmonary infections. Historically,
diverse murine inbred mouse strains and ex-vivo cellular models were considered
complementary to human studies for establishing the contribution of genetic
background to P. aeruginosa respiratory infections. More recently, the
development of a new mouse model of infection, mirroring human airway diseases,
combined with innovative murine resource populations, modelling human genetic
variation, provides additional insights into the mechanisms of genetic
susceptibility. In this review, we cover the recent state of the art of human and
animal studies and we discuss future potential challenges in the field of P.
aeruginosa respiratory infections.
PMID- 29947964
TI - An updated genetic map of Peromyscus with chromosomal assignment of linkage
groups.
AB - Species across the rodent genus Peromyscus have become prominent models for
studying diverse mechanistic and evolutionary processes, including chromosome
evolution, infectious disease transmission and human health, ecological
adaptation, coat color variation, and parental care. Supporting such diverse
research programs has been the development of genetic and genomic resources for
species within this genus, including genome data, interspecific chromosome
homologies, and a recently developed genetic map. Based on interspecific hybrids
between the deer mouse (Peromyscus maniculatus bairdii) and the old-field, or
beach, mouse (Peromyscus polionotus) and backcross progeny to Peromyscus
maniculatus, a linkage map was developed based on 190 genes and 141
microsatellite loci. However, resolution of several linkage groups with respect
to chromosome assignment was lacking and four chromosomes (8, 16, 20, and 21)
were not clearly delineated with linkage data alone. The recent development of a
high-density map for Peromyscus proved ineffective in resolving chromosome
linkage for these four chromosomes. Herein we present an updated linkage map for
Peromyscus maniculatus, including linkage group-chromosome assignments, using
fluorescence in situ hybridization mapping of BACs and whole chromosome paints.
We resolve the previously conflicting chromosome assignment of linkage groups to
Chromosomes 8, 16, 20, and 21, and confirm the assignment of linkage groups to
Chromosomes 18 and 22. This updated linkage map with validated chromosome
assignment provides a solid foundation for chromosome nomenclature for this
species.
PMID- 29947966
TI - Who are Pioneers of Disaster Preparedness? - Insights from Rainwater Harvesting
Dissemination in Bangladesh.
AB - This study deals with the roles of pioneers or early adopters in a rainwater
harvesting technology dissemination process in arsenic and water salinity
affected communities in coastal Bangladesh. The dissemination of such innovative
technologies has long been advocated for making disaster resilient communities,
but how to disseminate these innovations has rarely been addressed, except
heuristic studies limited to analyzing the cognitive factors of preparedness. We
argue that identifying and characterizing pioneer adopters is critical to promote
innovative disaster preventive technologies. Because pioneers take the risk to
adopt at a time when only limited information of the innovation is available,
and, based on their firsthand experience, other members can make prudent adoption
decisions. By using the social network threshold model, we show that just as
there are adopters at the macro or regional level, there are adopters at the
micro or local level, and they have the most critical roles, as catalysts to
disseminate disaster preventive technologies among the population. We also argue
that cosmopolitaness and level of education characterize the pioneers better,
rather than their income, risk awareness, and other personal features. Some
policy options related to the findings are also discussed.
PMID- 29947965
TI - Of mice and men: the host response to influenza virus infection.
AB - Influenza virus (IV) infections represent a very serious public health problem.
At present, no established biomarkers exist to support diagnosis for respiratory
viral infections and more importantly for severe IV disease. Studies in animal
models are extremely important to understand the biological, genetic, and
environmental factors that contribute to severe IV disease and to validate
biomarker candidates from human studies. However, mouse human cross-species
comparisons are often compromised by the fact that animal studies concentrate on
the infected lungs, whereas in humans almost all studies use peripheral blood
from patients. In addition, human studies do not consider genetic background as
variable although human populations are genetically very diverse. Therefore, in
this study, we performed a cross-species gene expression study of the peripheral
blood from human patients and from the highly genetically diverse Collaborative
Cross (CC) mouse population after IV infection. Our results demonstrate that
changes of gene expression in individual genes are highly similar in mice and
humans. The top-regulated genes in humans were also differentially regulated in
mice. We conclude that the mouse is a highly valuable in vivo model system to
validate and to discover gene candidates which can be used as biomarkers in
humans. Furthermore, mouse studies allow confirmation of findings in humans in a
well-controlled experimental system adding enormous value to the understanding of
expression and function of human candidate genes.
PMID- 29947967
TI - Towards Mechanistic Hydrological Limits: A Literature Synthesis to Improve the
Study of Direct Linkages between Sediment Transport and Periphyton Accrual in
Gravel-Bed Rivers.
AB - Altered hydrological, sediment, and nutrient regimes can lead to dramatic
increases in periphyton abundance in rivers below impoundments. Flushing flows
are a commonly adopted strategy to manage the excess periphyton that can
accumulate, but in practice they often prove ineffective. Designing hydrological
regimes that include flushing flows may be overlooking key processes in
periphyton removal, particularly the role of abrasion and molar action induced by
substrate movement. Setting flow targets which aim to initiate substrate movement
are likely to improve periphyton removal, but an understanding of the site
specific thresholds for substrate entrainment and periphyton removal is required.
Despite decades of entrainment studies accurate and consistent measurement and
prediction of substrate entrainment remains elusive, making it challenging to
study the relationship between substrate movement and periphyton removal, and to
set flow targets. This paper makes a case for using substrate entrainment and
transport thresholds as the target metric for flushing flows to manage excess
periphyton accrual. This paper critically reviews the determinants of periphyton
accrual and associated management methods. This paper also aims to provide a
reference for interdisciplinary research on periphyton removal by summarising the
geomorphic and hydraulic literature on methods for estimating and measuring
substrate entrainment and transport. This will provide a basis for ecologists to
identify tools for quantifying entrainment and transport thresholds so they are
better placed to explore the direct linkages between phases of sediment transport
and periphyton accrual. These linkages need to be identified in order for river
managers to set effective flushing flow targets.
PMID- 29947968
TI - Assessing the Effects of Fire Disturbances and Timber Management on Carbon
Storage in the Greater Yellowstone Ecosystem.
AB - Accurate characterization of Carbon (C) consequences of forest disturbances and
management is critical for informed climate mitigation and adaptation strategies.
While research into generalized properties of the forest C cycle informs policy
and provides abstract guidance to managers, most management occurs at local
scales and relies upon monitoring systems that can consistently provide C cycle
assessments that explicitly apply to a defined time and place. We used an
inventory-based forest monitoring and simulation tool to quantify C storage
effects of actual fires, timber harvests, and forest regeneration conditions in
the Greater Yellowstone Ecosystem (GYE). Results show that (1) the 1988 fires had
a larger impact on GYE's C storage than harvesting during 1985-2011; (2)
continuation of relatively high harvest rates of the region's National Forest
land, which declined after 1990, would have shifted the disturbance agent primary
importance on those lands from fire to harvest; and (3) accounting for local
heterogeneity of post-disturbance regeneration patterns translates into large
regional effects on total C storage. Large fires in 1988 released about 8.3 +/-
0.3 Mg/ha of C across Yellowstone National Park (YNP, including both disturbed
and undisturbed area), compared with total C storage reductions due to harvest of
about 2.3 +/- 0.3 Mg/ha and 2.6 +/- 0.2 Mg/ha in adjacent Caribou-Targhee and
Gallatin National Forests, respectively, from 1985-2011. If the high harvest
rates observed in 1985-1989 had been maintained through 2011 in GYE National
Forests, the C storage effect of harvesting would have quintupled to 10.5 +/- 1.0
Mg/ha, exceeding the immediate losses associated with YNP's historic fire but not
the longer-term net loss of carbon (16.9 +/- 0.8 Mg/ha). Following stand
replacing disturbance such as the 1988 fires, the actual regeneration rate was
slower than the default regional average rate assumed by empirically calibrated
forest growth models. If regeneration following the 1988 fire had reached
regionally average rates, either through different natural circumstances or
through more active management, YNP would have had approximately 4.1 Mg/ha more
forest carbon by year 2020. This study highlights the relative effects of fire
disturbances and management activities on regional C storage, and demonstrates a
forest carbon monitoring system that can be both applied consistently across the
US and tailored to questions of specific local management interest.
PMID- 29947969
TI - Chromatin mobility upon DNA damage: state of the art and remaining questions.
AB - Chromosome organization and chromatin mobility are central to DNA metabolism. In
particular, it has been recently shown by several labs that double strand breaks
(DSBs) in yeast induce a change in chromatin mobility at the site of the damage.
Intriguingly, DSB also induces a global mobility of the genome, at others,
potentially undamaged positions. How mobility is regulated and what are the
functional outcomes of these global changes in chromatin dynamics are, however,
not yet fully understood. We present the current state of knowledge in light of
the recent literature and discuss some perspectives opened by these discoveries
towards genome stability.
PMID- 29947970
TI - The transcription factor FgCrz1A is essential for fungal development, virulence,
deoxynivalenol biosynthesis and stress responses in Fusarium graminearum.
AB - The zinc finger transcription factor Crz1 is an important downstream regulator of
calcium-dependent signal transduction pathways in many organisms. The function of
Crz1 in the wheat-head blight pathogen Fusarium graminearum remains unclear. In
this study, we identified and functionally characterised FgCrz1A, a potential
ortholog of yeast Crz1. The deletion mutant DeltaFgCrz1A exhibited slower hyphal
growth on basic medium, and conidia formation and sexual reproduction were
completely blocked. DeltaFgCrz1A also displayed increased sensitivity to metal
cations Ca2+, Mg2+, Mn2+ and Li+, but decreased sensitivity to Zn2+.
Unexpectedly, the deletion mutant was more resistant to osmotic stress and cell
wall-damaging agents than the wild-type fungus. Pathogenicity assays showed that
virulence of the mutant was dramatically decreased on flowering wheat heads and
corn silks, consistent with the observed reduction in deoxynivalenol production.
Moreover, GFP-fused FgCrz1A was mainly localised in the nucleus, and was required
for transcriptional induction of abaA and wetA that are involved in
conidiogenesis, as well as genes of the MAT locus during sexual reproduction, and
TRI genes responsible for deoxynivalenol biosynthesis. Taken together, the
results indicate that FgCrz1A plays critical roles not only in regulating fungal
development, secondary metabolism and virulence in F. graminearum, but also in
multiple stress responses.
PMID- 29947971
TI - A bacterial signaling system regulates noise to enable bet hedging.
AB - Phenotypic diversity helps populations persist in changing and often
unpredictable environments. One diversity-generating strategy is for individuals
to switch randomly between phenotypic states such that one subpopulation has high
fitness in the present environment, and another subpopulation has high fitness in
an environment that might be encountered in the future. This sort of biological
bet hedging can be found in all domains of life. Here, we discuss a recently
described example from the bacterium Escherichia coli. When exposed to both
oxygen and trimethylamine oxide (TMAO), E. coli hedges its bets on the
possibility of oxygen loss by generating high cell-to-cell variability in the
expression of the TMAO respiratory system. If oxygen is rapidly depleted from the
environment, only those cells that had been expressing the TMAO respiratory
system at high levels can continue to grow. This particular bet-hedging scheme
possesses some unusual characteristics, most notably the decoupling of gene
expression noise from the mean expression level. This decoupling allows bacteria
to sense oxygen and regulate the amount of variability in TMAO reductase
expression (that is, to turn bet hedging on or off) without having to adjust the
mean TMAO reductase expression level. In this review, we discuss the features of
the TMAO signaling pathway that permit the decoupling of gene expression noise
from the mean and the regulation of bet hedging. We also highlight some open
questions regarding the TMAO respiratory system and its regulatory architecture
that may be relevant to many signaling systems.
PMID- 29947972
TI - Efficacy and safety of mesenchymal stromal cells for the prophylaxis of chronic
graft-versus-host disease after allogeneic hematopoietic stem cell
transplantation: a meta-analysis of randomized controlled trials.
AB - A meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate
the efficacy and safety of mesenchymal stromal cells (MSCs) for the prophylaxis
of chronic graft-versus-host disease (cGVHD) in patients with hematological
malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo
HSCT). Six studies involving 365 patients were included. The pooled results
showed that MSCs significantly reduced the incidence of cGVHD (risk ratio [RR]
0.63, 95% confidence interval [CI] 0.46 to 0.86, P = 0.004). Favorable
prophylactic effects of MSCs on cGVHD were observed with umbilical cord-derived,
high-dose, and late-infusion MSCs, while bone marrow-derived, low-dose, and
coinfused MSCs did not confer beneficial prophylactic effects. In addition, MSC
infusion did not increase the risk of primary disease relapse and infection (RR
1.02, 95% CI 0.70 to 1.50, P = 0.913; RR 0.89, 95% CI 0.44 to 1.81, P = 0.752;
respectively). Moreover, there was an apparent trend toward increased overall
survival (OS) in the MSC group compared with that in the control group (RR 1.13,
95% CI 0.98 to 1.29, P = 0.084). In conclusion, this meta-analysis demonstrated
that MSC infusion is an effective and safe prophylactic strategy for cGVHD in
patients with hematological malignancies undergoing allo-HSCT.
PMID- 29947973
TI - Comparative analysis of azacitidine and intensive chemotherapy as front-line
treatment of elderly patients with acute myeloid leukemia.
AB - The present observational study aimed to compare the efficacy of azacitidine
(AZA) and intensive chemotherapy (IC) in elderly patients with untreated acute
myeloid leukemia (AML), diagnosed according to WHO criteria. In the two groups,
we evaluated complete remission (CR), overall survival (OS), and disease-free
survival (DFS). The AZA group included 89 patients; median age was 73 years
(range 61-80) and median white blood cell count (WBCc) 2.5 * 109/L (range 0.27
83), 45% of the patients had BM blasts >= 30%, and 44 (49%) had a secondary AML
(sAML). Karyotype was evaluable in 69 patients: 51 (74%) had intermediate-risk
abnormalities and 18 (26%) an unfavorable risk karyotype. IC group consisted of
110 patients who received an induction course with mitoxantrone, cytarabine, and
etoposide, followed by two consolidation cycles including idarubicin, cytarabine,
and etoposide. Median age was 67 years (range 61-78) and median WBCc 8.0 * 109/L
(range 0.69-258); 44 (40%) had a sAML. Karyotype was evaluable in 88 patients, 71
(81%) had intermediate risk, and 17 (19%) unfavorable risk karyotype. To minimize
the effects of treatment selection bias, adjustments were made using the
propensity-score matching method, which yielded 74 patient pairs. CR rate was
significantly higher in IC vs AZA group (73 vs 25%, respectively) (p < 0.0001),
but the 3-year OS rates and median OS were not significantly different (21.6 vs
11% and 15.8 vs 13 months, respectively). Our analysis suggests similar outcomes
with AZA compared to IC. Controlled, randomized clinical trials are warranted to
confirm this conclusion.
PMID- 29947974
TI - Treating synchronous bilateral ocular adnexal marginal zone lymphoma: the
consortium for improving survival of lymphoma study.
AB - Both-side synchronous involvement has been reported to account for 7-24% of
ocular adnexal marginal zone lymphoma (OAML). We conducted a retrospective
analysis to identify the clinical features and treatment outcomes of synchronous
bilateral OAML (SB-OAML) by treatment modality. We analyzed patients with a
histologic diagnosis of SB-OAML, excluding metachronous bilateral involved OAML.
We enrolled a total of 95 patients for this analysis, 36 males and 59 females;
the median patient age was 42 years (range 16-77 years). Eleven (11.6%) patients
had been treated with chemotherapy or chemo-immunotherapy (eight R-CVP, two CVP,
and one R-CHOP). The median number of treatments was 6 (range 6-8); there were 9
complete responses (CRs; 81.8%) and 2 partial responses (PRs; 18.2%). Nearly all
patients (88.4%) received radiotherapy in both eyes, and the median radiation
dose was 27 Gy (range 20-40 Gy) to each eye; 68 CRs (80.9%) and 14 PRs (16.7%)
were achieved. Ten-year progression-free survival (PFS) and overall survival (OS)
rates were 79.8 and 91.1%, respectively. Radiotherapy continued to be an
independent prognostic marker, with the hazard of progression (P = 0.036). Eleven
patients (13.1%) had surgery for cataract treatment during follow-up, and
patients who received low-dose radiation (< 30.3 Gy) experienced fewer cataract
operations. SB-OAML was predominantly observed in young females, and they had
good response and prognosis regardless of treatment modalities. Low-dose
radiotherapy to both eyes showed a tendency of longer PFS than did chemotherapy
and could decrease cataract operations.
PMID- 29947975
TI - Fludarabine and busulfan plus low-dose TBI as reduced intensity conditioning in
older patients undergoing allogeneic hematopoietic cell transplant for myeloid
malignancies.
AB - We have been using a combination of fludarabine/busulfan plus low-dose total body
irradiation (TBI) as the reduced-intensity conditioning (RIC) regimen for
patients age >= 60 years undergoing allogeneic hematopoietic cell transplantation
(HCT) for myeloid malignancies. We retrospectively analyzed outcomes of 116 older
patients (median age 64 years) who underwent HCT from 2006 to 2015 for myeloid
malignancies, including acute myeloid leukemia (AML) in first complete remission
(CR1). On univariate analysis, overall survival (OS) for the cohort at 3 years
was 33% (95% CI 25-42). Cumulative incidence of relapse (CIR) and non-relapse
mortality (NRM) at 3 years were 24% (95% CI 16-32) and 43% (95% CI 34-52),
respectively. Multivariable analysis for OS demonstrated AML patients to have
superior outcome (HR 1.60 for other myeloid, 95% CI 1.01-2.54, p = 0.045), as
well as related donors (HR 1.92 for unrelated, 95% CI 1.22-3.03, p = 0.005). For
NRM, AML patients had superior outcome (HR 1.76 for other myeloid, 95% CI 1.03
3.01, p = 0.038), as well as patients with related donors (HR 1.81 for unrelated,
95% CI 1.07-3.07, p = 0.028). We then demonstrated that AML patients with related
donors (n = 45) had superior 3-year OS of 51% (95% CI 36-65), compared to 21%
(95% CI 12-32) for all other patients (p = 0.0003). We conclude that the RIC
regimen used is effective for older patients, particularly AML patients in CR1
with matched related donors.
PMID- 29947976
TI - Diagnosis of Richter transformation in chronic lymphocytic leukemia: histology
tips the scales.
AB - Development of diffuse large B-cell lymphoma in chronic lymphocytic leukemia, so
called Richter transformation (RT), occurs in 2-5% of patients and is associated
with poor outcome. The clinical features of RT are fairly non-specific and unable
to discriminate transformation from other mimics. In case of clinically suspected
RT, a CT/MRT is recommended, and FDG-PET/CT may help to select the site of
biopsy. Radiological features suggestive of RT have been defined, but there are
only limited data about their predictive value, and histological confirmation is
still considered the gold standard for RT diagnosis. We retrospectively analyzed
34 patients with clinically suspected RT and available radiological and
histological data. A histopathological diagnosis of RT with concordant clinical
and radiological findings was obtained in 13 patients. In 18 patients, CT did not
show features of transformation, concordant with lack of RT in the biopsy. Of
interest, a distinct lymphoma other than DLBCL was identified in two of these
cases. A false-positive radiological diagnosis of RT was rendered in two
patients, including a case of Herpes simplex virus lymphadenitis. In conclusion,
our findings confirm the central role of tissue biopsy in the diagnostic work up
in case of clinically suspected RT.
PMID- 29947978
TI - Correction to: Meeting Abstracts from the 1st Congress of the Ambroise Pare
International Military Surgery Forum (APIMSF): 30th Anniversary APIMSF Meeting,
Baku, Azerbaijan, May 15-18, 2018.
AB - Following are corrections to this abstract supplement.
PMID- 29947977
TI - Allogeneic hematopoietic cell transplantation in patients with GATA2 deficiency-a
case report and comprehensive review of the literature.
AB - Recently, an immunodeficiency syndrome caused by guanine-adenine-thymine-adenine
2 (GATA2) deficiency has been described. The syndrome is characterized by (i)
typical onset in early adulthood, (ii) profound peripheral blood cytopenias of
monocytes, B lymphocytes, and NK cells, (iii) distinct susceptibility to
disseminated non-tuberculous mycobacterial (NTM) and other opportunistic
infections (particularly human papillomavirus), and (iv) a high risk of
developing hematologic malignancies (myelodysplastic syndromes (MDS); acute
myeloid leukemias (AML)). Considerable clinical heterogeneity exists among
patients with GATA2 deficiency, but once infectious symptoms occur or MDS/AML
arises, survival declines significantly. Allogeneic hematopoietic cell
transplantation (HCT) currently provides the only curative treatment option for
both MDS/AML and dysfunctional immunity with life-threatening opportunistic
infections. Strategies regarding timing of allogeneic HCT, antimicrobial
prophylaxis and treatment, intensity of the preparative regimen, and optimal
donor and graft source have not been clearly defined due to the rarity of the
disease. Here, we provide a comprehensive analysis of the available literature
and published case reports on the use of allogeneic HCT in patients with GATA2
deficiency. In addition, a case of a young woman with GATA2 deficiency, who
developed an immune reconstitution inflammatory syndrome in her mycobacterial
skin lesions post allogeneic HCT is presented and illustrates distinct problems
encountered in this disease context.
PMID- 29947979
TI - Welcome New Associate Editor David Watson of Australia.
PMID- 29947980
TI - Liver Resection for Hepatocellular Carcinoma in Patients with Renal Dysfunction.
AB - BACKGROUND: The aim of this study was to evaluate the feasibility of liver
resection in hepatocellular carcinoma (HCC) patients with preoperative renal
dysfunction (RD). METHODS: Data from 735 patients undergoing primary liver
resection for HCC between 2002 and 2014 were analyzed. Short- and long-term
outcomes were compared between the RD group, defined by a preoperative estimated
glomerular filtration rate of <45 mL/min/1.73 m2, and the non-RD group. RESULTS:
Sixty-two patients had RD. The incidence of postoperative pleural effusion (24
vs. 11%; P = 0.007) and major complications (Clavien-Dindo III-V; 31 vs. 15%; P =
0.003) were significantly higher in RD patients. In RD patients with Child-Pugh
A, 90-day mortality rate (1.9%) and median survival time (6.11 years) were
comparable to that of non-RD patients. In contrast, RD patients with Child-Pugh B
had a very high 90-day mortality rate (22.2%), and a significant shorter median
survival time compared to non-RD patients (1.19 vs. 4.84 years; P = 0.001).
CONCLUSIONS: Liver resection for Child-Pugh A patients with RD is safe and has
comparable oncological outcomes compared to non-RD patients. However, selection
of liver resection candidates from Child-Pugh B patients with RD should be
stricter.
PMID- 29947981
TI - Authors' Reply: Risk Factors for Mortality and Morbidity in Elderly Patients
Presenting with Digestive Surgical Emergencies.
PMID- 29947982
TI - Joint Statement by the Surgery Journal Editors Group.
PMID- 29947983
TI - Cost Incurred by the Family for Surgery in Their Children: A Bangladesh
Perspective.
AB - BACKGROUND: Cost of getting health services is a major concern in Bangladesh as
well as in many other countries. A family has to bear more than half of the
health care cost despite many facilities provided by the public hospitals. This
out-of-pocket (OOP) expenditure drives many families under the poverty line. The
aim of this study was to find out the exact cost incurred by the family for a
surgical operation of their child in the public and private sectors in
Bangladesh. METHODS: A cross-sectional study was conducted to find out the cost
of child surgery in different settings of public and private hospitals in
Chittagong division, Bangladesh. Cost of herniotomy was then compared across
different settings. RESULTS: In this study, cost of operation in urban private
hospitals was highest mostly due to surgeon and anesthetist fee. The cost was
lowest in outreach programs as surgeon fee, anesthetist fee and accommodation
cost was nil; food and transport cost was minimum. However, cost of
accommodation, food, transport and medicine contributed significantly to OOP
expenditure especially in tertiary-level public hospitals, in both indoor and day
care settings, and also in private urban hospitals. CONCLUSIONS: Our study
provides some insight into the OOP expenditure in different health care settings
in Bangladesh. This study might be useful in developing a strategy to minimize
the OOP expenditure in this country.
PMID- 29947984
TI - Correction to: The Surgical Teams' Perception of the Effects of a Routine
Intraoperative Pause.
AB - In the original article there is an error in the legend in Fig. 4. Following is
corrected Fig. 4.
PMID- 29947985
TI - Liver Regeneration is Preserved After At Least Four Repeated Liver Resections for
Hepatocellular Carcinoma.
AB - INTRODUCTION: Repeated resection is known to prolong survival, with an acceptable
morbidity rate, in patients with hepatocellular carcinoma. However, little is
known about the effect of repeated liver resection on postoperative liver
regeneration and liver function. The aim of this study is to determine the impact
of repeated liver resections on the postoperative liver regeneration rate and
liver function. METHODS: A total of 71 patients, who had undergone more than
three liver resections for hepatocellular carcinoma between May 2001 and December
2013 at a tertiary care hospital in Japan, were included in the analysis. Among
them, CT-volumetric data for the first, second, third, and fourth or more
resections were available for 36, 49, 53, and 24 patients. We analyzed the
regeneration index (RI) defined as the postoperative TLV/preoperative TLV * 100
was calculated after each operation to measure the degree of regeneration. Liver
function was evaluated using the indocyanine green retention rate at 15 min (ICG
R15). RESULTS: No significant differences in RI were observed among the first,
second, and third or more liver resection groups. No significant difference in
the ICG R15 value was seen between the first liver resection group and the second
or more liver resection group (P = 0.75). However, a significant difference in
the RI was observed when the 1 segmentectomy or less liver resection group
(median [range] RI 98.1 [72.9-119.9]) was compared with the 2 or more
segmentectomy group (median [range] RI 90.5 [62.6-113.6]) (P = 0.005).
CONCLUSION: The regeneration process is maintained after as many as four repeated
resections. Patients with sustained liver function can safely undergo repeated
liver resections for recurrences of HCC.
PMID- 29947986
TI - Implementation of the World Health Organization Surgical Safety Checklist
Correlates with Reduced Surgical Mortality and Length of Hospital Admission in a
High-Income Country.
AB - BACKGROUND: The World Health Organization Surgical Safety Checklist (WHO SSC) has
been widely implemented in an effort to decrease surgical adverse events. The
effects of the checklist on postoperative outcomes have not previously been
examined in Australia, and there is limited evidence on the effects of the
checklist in the long term. METHODS: A retrospective review was conducted using
administrative databases to examine the effects of the implementation of the
checklist on postoperative outcomes. Data from 21,306 surgical procedures,
performed over a 5-year time period at a tertiary care centre in Australia where
the WHO SSC was introduced in the middle of this period, were analysed using
multivariate logistic regression. RESULTS: Postoperative mortality rates
decreased from 1.2 to 0.92% [p = 0.038, OR 0.74 (0.56-0.98)], and length of
admission decreased from 5.2 to 4.7 days (p = 0.014). The reduction in mortality
rates reached significance at the 2-3 years post-implementation period [p =
0.017, OR 0.61 (0.41-0.92)]. The observed decrease in mortality rates was
independent of the surgical procedure duration. CONCLUSION: Implementation of the
WHO SSC was associated with a statistically significant reduction in mortality
and length of admission over a 5-year time period. This is the first study
demonstrating a reduction in postoperative mortality after the implementation of
the checklist in an Australian setting. In this study, a relatively longer period
examined, comparative to previous international studies, may have allowed factors
like surgical culture change to take effect.
PMID- 29947987
TI - Orthopaedic Surgeon Density in South Africa.
AB - BACKGROUND: In the era of global surgery, there are limited data regarding the
available surgical workforce in South Africa. METHODS: This aim of this study was
to determine the orthopaedic surgeon density in South Africa. This involved a
quantitative descriptive analysis of all registered specialist orthopaedic
surgeons in South Africa, using data collected from various professional societal
national databases. RESULTS: The results showed 1.63 orthopaedic surgeons per
100,000 population. The vast majority were male (95%) with under two-thirds (65%)
being under the age of 55 years. The majority of the orthopaedic surgeons were
found in Gauteng, followed by the Western Cape and Kwa-Zulu Natal. The majority
of specialists reportedly worked either full time or part time in the private
sector (95%), and the orthopaedic surgeon density per uninsured population (0.36)
was far below that of the private sector (8.3). CONCLUSION: Interprovincial
differences as well as intersectoral differences were marked indicating
geographic and socio-economic maldistribution of orthopaedic surgeons. This
parallels previous studies which looked at other surgical sub-disciplines in
South Africa. Addressing this maldistribution requires concerted efforts to
expand public sector specialist posts as well as quantifying the burden of
orthopaedic disease in both private and public sectors before recommendations can
be made regarding workforce allocation in the future. LEVEL OF EVIDENCE: IV.
PMID- 29947989
TI - Laparoscopic Partial Sleeve Duodenectomy for the Infra-Ampullary Gastrointestinal
Stromal Tumors of the Duodenum.
AB - BACKGROUND: Although organ-preserving operations are regarded as effective
strategies for duodenal gastrointestinal stromal tumors (GISTs), laparoscopic
partial sleeve duodenectomy (lap PSD) has not been fully evaluated. The aims of
this study were to evaluate the effectiveness and technical feasibility of lap
PSD. STUDY DESIGN: Between January 2011 and March 2016, we reviewed 13 patients
who underwent laparoscopic approach among 22 patients who underwent PSD. PSD for
the infra-ampullary lesions was defined as infra-ampullary duodenal resection
including the first portion of the jejunum. After resection, all patients
underwent reconstruction via side-to-side duodenojejunostomy. RESULTS: The total
mean operation time was 273 min (range 160-346 min), and estimated mean blood
loss was 80 ml (range scanty-200 ml). One patient was converted to open
laparotomy because of mesocolonic tumor involvement. The median postoperative
hospital stay was 10.5 days (range 4-36 days). There were no postoperative
mortalities. Postoperative complications included 2 instances of delayed gastric
emptying (DGE), 1 duodenojejunostomy stricture, and 2 intestinal obstructions. No
patient was treated with adjuvant therapy. One patient experienced hepatic
metastasis 28 months after surgery during a mean follow-up period of 48.6 months.
CONCLUSION: Lap PSD might be an oncologically effective strategy for duodenal
GIST, and the laparoscopic approach is a technically feasible and appealing
surgical modality in terms of safety and perioperative results. However, DGE and
anastomosis strictures are concerns for postoperative complications, which need
to be further investigated.
PMID- 29947988
TI - Magnetic Anastomosis for Biliojejunostomy: First Prospective Clinical Trial.
AB - BACKGROUND: Magnetic compression anastomosis (magnamosis, MCA) has been verified
safe and effective by us and others in animal bilioenteric anastomosis (BEA). The
objective of the present study was to introduce clinical application of magnetic
compression bilioenteric anastomosis (MC-BEA) with a unique device in series of
patients. METHODS: Patients with obstructive jaundice with an indication of BEA
were prospectively enrolled from 2012 to 2015. After dissection of bile ducts,
the mother ring and drainage tube were placed in the proximal bile duct and the
purse-string suture was tightened over the drainage tube. The drainage tube was
introduced into the jejunal lumen at the anastomotic site and used to guide the
daughter ring to assemble with the mother ring. All the patients were routinely
followed up for magnets discharge or any complications associated. RESULTS: Forty
one patients were included. Thirty-four (82.9%) patients had a malignant primary
disease, while seven (17.1%) had benign disease. The median time for MC-BEA was
10.5 min (interquartile range [IQR] 8.3-13.0 min). No perioperative morbidity or
mortality associated with MC-BEA was observed. The median time for a patent
bilioenteric anastomosis formation was 19.0 days (IQR 14.5-23.0 days), and the
magnets were discharged with a median postoperative duration of 35.0 days (IQR
28.0-43.0 days). With a median follow-up of 547.5 days (range 223-1042 days), no
patients had biliary fistula, while two (4.9%) developed anastomotic stricture at
4 months and 14 months after surgery, and underwent reoperation for
reconstruction of BEA. CONCLUSIONS: MCA is a safe, effective, and time-saving
modality for biliojejunostomy.
PMID- 29947990
TI - Prospective Risk Factor Analysis for the Development of Post-operative Urinary
Retention Following Ambulatory General Surgery.
AB - AIMS: Post-operative urinary retention (POUR) is a common cause of unplanned
admission following day-case surgery and has negative effects on both patient and
surgical institution. We aimed to prospectively evaluate potential risk factors
for the development of POUR following day-case general surgical procedures.
METHODS: Over a 24-week period, consecutive adult patients undergoing elective
day-case general surgery at a single institution were prospectively recruited.
Data regarding urinary symptoms, comorbidities, drug history, surgery and
perioperative anaesthetic drug use were collected. The primary outcome was the
incidence of POUR, defined as an impairment of bladder voiding requiring either
urethral catheterisation, unplanned overnight admission or both. Potential risk
factors for the development of POUR were analysed by logistic regression.
RESULTS: A total of 458 patients met the inclusion criteria during the study
period, and data were collected on 382 (83%) patients (74.3% male). Sixteen
patients (4.2%) experienced POUR. Unadjusted analysis demonstrated three
significant risk factors for the development of POUR: age >= 56 years (OR 7.77
[2.18-27.78], p = 0.002), laparoscopic surgery (OR 3.37 [1.03-12.10], p = 0.044)
and glycopyrrolate administration (OR 5.56 [2.00-15.46], p = 0.001). Male sex and
lower urinary tract symptoms were not significant factors. Multivariate analysis
combining type of surgery, age and glycopyrrolate use revealed that only age >=
56 years (OR 8.14 [2.18-30.32], p = 0.0018) and glycopyrrolate administration (OR
3.48 [1.08-11.24], p = 0.0370) were independently associated with POUR.
CONCLUSIONS: Patients aged at least 56 years and/or requiring glycopyrrolate
often administered during laparoscopic procedures-are at increased risk of POUR
following ambulatory general surgery.
PMID- 29947992
TI - Amelioration of hyperoxaluria-induced kidney dysfunction by chemical chaperone 4
phenylbutyric acid.
AB - Hyperoxaluria is characterized by an increased excretion of urinary oxalate which
is caused by inherited disorders or high oxalate intake leading to renal stone
ailment. Until date, reactive oxygen species and inflammation has been convicted
for the progression of kidney stones for which antioxidant therapy has been
employed. However, recent studies have linked the association of endoplasmic
reticulum stress and oxidative imbalance in the progression of renal diseases.
Considering oxidative stress being at forefront in causing hyperoxaluric
consequences, current study was designed to correlate the impact of hyperoxaluria
and regulation of oxidative imbalance via inhibition of endoplasmic reticulum
stress by 4-phenylbutyric acid (4-PBA). Male wistar rats were subdivided into
three groups, i.e., normal control (C), hyperoxaluric rats given ethylene glycol
(EG), and hyperoxaluric rats treated with 4-PBA (EG + PBA). After 28 days of
treatment, assessment of antioxidant defence system, inflammation, ER stress, and
subsequent unfolded protein response was studied in renal tissue. It was found
that the hyperoxaluric insult led to a marked damage to the renal tissue
resulting in compromised antioxidant levels, upregulation of ER stress markers
along with a steep surge in the extent of inflammation. However, 4-PBA treatment
significantly curtailed the deleterious effects of hyperoxaluria by lowering down
the level of stress markers as well as normalizing the antioxidant defence
enzymes. Therefore, chemical chaperones can be deemed as a new class of drugs for
the treatment of hyperoxaluric induced renal damage.
PMID- 29947991
TI - Primary Tumor Versus Liver-First Approach for Synchronous Colorectal Liver
Metastases: An Association Francaise de Chirurgie (AFC) Multicenter-Based Study
with Propensity Score Analysis.
AB - OBJECTIVES: Multicenter studies comparing the reverse strategy (RS) with the
classical strategy (CS) for the management of stage IVA liver-only colorectal
cancer (CCR) are scarce. The aim of this study was to compare long-term survival
and recurrence patterns following use of the CS and RS. METHOD: This
retrospective multicenter review collected data from all consecutive patients
with stage IVA liver-only CCR who underwent staged resection of CCR and liver
metastases (LM) at 24 French hospitals between 2006 and 2013 and were
retrospectively analyzed. Patients who underwent simultaneous liver and CCR
resection, those with synchronous extrahepatic metastasis, and those who
underwent emergent CCR resection were excluded. Overall survival (OS) and
recurrence-free survival (RFS) rates and recurrence patterns were investigated
before and after propensity score matching (PSM). RESULTS: A total of 653
patients were included: 587 (89.9%) in the CS group and 66 (10.1%) in the RS
group. Compared with the CS patients, RS patients were more likely to have rectal
cancer (43.9 vs. 24.9%; p = 0.006), larger liver tumor size (52.5 +/- 38.6 vs.
39.6 +/- 30 mm; p = 0.01), and more positive lymph nodes (62.1 vs. 44.8%; p =
0.009). OS was not different between the two groups (75 vs. 72% at 5 years; p =
0.77), while RFS was worse in the RS group (24 vs. 33% at 5 years; p = 0.01).
Time to recurrence at any site (1.8 vs. 2.4 years, p = 0.024) and intrahepatic
recurrence (1.7 vs. 2.2 years, p = 0.014) were significantly shorter in the RS
group than in the CS group. After PSM (63 patients in each group), no significant
difference was found between the two groups in OS (p = 0.35), RFS (p = 0.62),
time to recurrence at any site (p = 0.19), or intrahepatic recurrence (p = 0.13).
CONCLUSIONS: In this study, approximately 10% of patients with CCR and
synchronous LM were offered surgery with the RS. Both strategies ensured similar
oncological outcomes.
PMID- 29947993
TI - Oxalate transport by the mouse intestine in vitro is not affected by chronic
challenges to systemic acid-base homeostasis.
AB - In rats, we recently showed how a chronic metabolic acidosis simultaneously
reduced urinary oxalate excretion and promoted oxalate secretion by the distal
colon leading to the proposition that acid-base disturbances may trigger changes
to renal and intestinal oxalate handling. The present study sought to reproduce
and extend these observations using the mouse model, where the availability of
targeted gene knockouts (KOs) would offer future opportunities to reveal some of
the underlying transporters and mechanisms involved. Mice were provided with a
sustained load of acid (NH4Cl), base (NaHCO3) or the carbonic anhydrase inhibitor
acetazolamide (ATZ) for 7 days after which time the impacts on urinary oxalate
excretion and its transport by the intestine were evaluated. Mice consuming NH4Cl
developed a metabolic acidosis but urinary oxalate was only reduced 46% and not
statistically different from the control group, while provision of NaHCO3
provoked a significant 2.6-fold increase in oxalate excretion. For mice receiving
ATZ, the rate of urinary oxalate excretion did not change significantly.
Critically, none of these treatments altered the fluxes of oxalate (or chloride)
across the distal ileum, cecum or distal colon. Hence, we were unable to produce
the same effects of a metabolic acidosis in mice that we had previously found in
rats, failing to find any evidence of the 'gut-kidney axis' influencing oxalate
handling in response to various acid-base challenges. Despite the potential
advantages offered by KO mice, this model species is not suitable for exploring
how acid-base status regulates oxalate handling between the kidney and intestine.
PMID- 29947994
TI - The role of super-mini percutaneous nephrolithotomy (SMP) in the treatment of
symptomatic lower pole renal stones (LPSs) after the failure of shockwave
lithotripsy (SWL) or retrograde intrarenal surgery (RIRS).
AB - To assess the safety and efficacy of super-mini percutaneous nephrolithotomy
(SMP) in the treatment of symptomatic lower pole renal stones (LPSs) after the
failure of shockwave lithotripsy (SWL) or retrograde intrarenal surgery (RIRS),
we retrospectively evaluated 44 patients with symptomatic LPSs with previously
failed SWL or RIRS and consequently underwent SMP from October 2014 to March
2016. The percutaneous renal access was performed 12-14F with C-arm fluoroscopy
or ultrasonographic guidance. Stone disintegration was performed using either
Holmium laser or pneumatic lithotripter. Perioperative parameters along with
operations were assessed in detail. A total of 44 patients (mean age 49.1 +/-
13.7 years) were included in the study. Stone size was 18.4 +/- 6.0 mm (range 9
29), operative time was 63.9 +/- 32.7 min (range 14-145) and hospital stay was
2.8 +/- 1.2 days (range 1-5). The hemoglobin drop was 12.4 +/- 8.8 g/L (range 0
31), and no patients required blood transfusion. Complete stone-free status was
achieved in 40 (90.9%) patients. Clinically insignificant residual fragments were
observed in three (6.8%) patients and only one (2.3%) patient had a 6 mm residual
calculus. A total of three minor complications (urinary tract infection,
hemorrhage resolved by hemostatics and renal colic requiring analgesics) were
observed postoperatively. For symptomatic LPSs after the failure of SWL or RIRS,
SMP is a safe and efficient auxiliary option and even might be an alternative to
SWL or RIRS, while further considering the stone-free rates and stone-related
events.
PMID- 29947995
TI - Analyses of long non-coding RNA and mRNA profiling using RNA sequencing in
calcium oxalate monohydrate-stimulated renal tubular epithelial cells.
AB - To study the expression profiles of lncRNA and mRNA in the calcium oxalate
monohydrate-attached HK-2 cells, and investigate the association between critical
lncRNA expression level and renal injury. The HK-2 cells were treated with
crystal suspension of calcium oxalate. The effects of calcium oxalate crystals on
the growth of HK-2 cells were determined by MTT assay. Total RNA was extracted
and the lncRNA and mRNA expression profiles were analyzed by high-throughput
transcriptase sequencing platform HiSeq 2500. The profile of identified lncRNAs
and mRNAs were verified by real-time PCR and their potential function was
analyzed by Gene Ontology database and KEGG signal pathway analysis. Calcium
oxalate crystals adhered to the surface of HK-2 cells in few minutes and showed
obvious cytotoxicity. RNA seq results showed that there were 25 differentially
expressed lncRNAs in HK-2 cells treated with calcium oxalate crystals, of which 9
were up-regulated and 16 were down-regulated. The difference was verified by real
time PCR which showed statistically significant (P < 0.05). Calcium oxalate
crystals have a significant effect on lncRNA and mRNA expression in human renal
epithelial cells, which may play critical roles in kidney stone-mediated renal
injury.
PMID- 29947996
TI - An in vitro evaluation of laser settings and location in the efficiency of the
popcorn effect.
AB - To examine different locations and laser settings' effects on the efficiency of
the "popcorn" method of laser lithotripsy, which consists of placing the laser in
a group of small stones and firing continuously to break them into smaller
particles. Pre-fragmented BegoStones were created between 2 and 4 mm to mimic
typical popcorning conditions. A 0.5 g collection of fragments was placed into 3D
printed models (a spherical calyx and ellipsoid pelvis model) and a 200-um laser
fiber was positioned above the stones. The laser was fired for 2 min with
irrigation, with 5 trials at each setting: 0.2 J/50 Hz, 0.5 J/20 Hz, 0.5 J/40 Hz,
1 J/20 Hz, 0.2 J/80 Hz, 0.5 J/80 Hz. After drying, fragmentation efficiency was
determined by calculating the mass of stones reduced to sub-2 mm particles.
Statistical analysis was performed with ANOVA and Student's t test. The trials
within the calyx model were significantly more efficient compared to the pelvis
(0.19 vs 0.15 g, p = 0.01). When comparing laser settings, there was a difference
between groups by one-way ANOVA [F(5,54) = 8.503, p = 5.47 * 10-6]. Post hoc
tests showed a power setting of 0.5 J/80 Hz was significantly more efficient than
low-power settings 0.2 J/50 Hz and 0.5 J/20 Hz (p < 0.05). Additionally, 0.2 J/50
Hz was significantly less efficient than 0.5 J/40 Hz, 1 J/20 Hz, and 0.2 J/80 Hz.
Popcorning is most efficient in smaller spaces; we recommend displacement of
stones into a calyx before popcorning. No difference was seen between high-power
settings, although 0.5 J/40 Hz and 0.5 J/80 Hz performed best, suggesting that
moderate energy popcorning methods with at least 0.5 J per pulse are most
efficient.
PMID- 29947997
TI - Leptin as an obesity marker in rheumatoid arthritis.
AB - The determination of excess of body fat mass provides a more suitable determinant
of obesity in rheumatoid arthritis patients; however, body mass index (BMI) may
not be accurate for the quantification of adiposity. To identify a marker of
excess adiposity in women with rheumatoid arthritis (RA) using different methods
for fat mass evaluation. A cross-sectional study was conducted in adult female
patients with RA. Disease activity was assessed by DAS28-ESR, and obesity was
determined by waist circumference (WC), BMI and dual-energy X-ray absorptiometry
(DXA). The Human Bone Metabolism kit (Merck Millipore, Darmstadt, Alemanha) was
used to determine the plasma levels of leptin, TNF-alpha, IL-6, and IL-1beta by
quantification of serum proteins by technical microspheres (LUMINEX, TX, USA).
Adiponectin was measured by enzyme-linked immunosorbent assay sandwich kit (R&D
Systems, Minneapolis, MN, USA). Eighty-nine female patients, median age of 55.4
(+/- 11.6) years, and median disease duration of 16.4 (+/- 14.9) years were
included. The frequency of obesity was 33.7% according to BMI, 89.9% with WC, and
56.1% with DXA. The median serum leptin concentration was the only marker that
correlated with body fat percentage according to the three methods. This
correlation was positive and not influenced by DAS28, C-reactive protein,
erythrocyte sedimentation rate, or inflammatory cytokines levels (IL-6, TNF
alpha, IL-1beta). Analysis of ROC curves determined the cut-off point of 10.3
ng/mL of leptin as an obesity marker, with a sensitivity of 96.43% and a
specificity of 23.81%. Serum leptin correlates positively with fat mass and is
potentially useful in excess fat mass determination in clinical practice.
PMID- 29947999
TI - Effects of balneotherapy and spa therapy on quality of life of patients with knee
osteoarthritis: a systematic review and meta-analysis.
AB - Knee osteoarthritis (OA) is a degenerative disease which is expected to become
one of the leading causes of disability by the next years. This work aims to
assess if balneotherapy and spa therapy can significantly improve Quality of Life
(QoL) of patients with knee OA. Medline via PubMed, Scopus, Web of Science,
Cochrane Library, and PEDro were systematically searched for articles about
trials involving patients with knee OA and measuring the effects of balneotherapy
and spa therapy on study participants' QoL with validated scales. A qualitative
and quantitative syntheses were performed. Seventeen studies were considered
eligible and included in the systematic review. Fourteen trials reported
significant improvements in at least one QoL item after treatment. Ten studies
were included in quantitative synthesis. When comparing balneological
interventions with standard treatment, results favored the former in terms of
long-term overall QoL [ES = - 1.03 (95% CI - 1.66 to - 0.40)]. When comparing
balneological interventions with sham interventions, results favored the former
in terms of long-term pain improvement [ES = - 0.38 (95% CI - 0.74 to - 0.02)],
while no significant difference was found when considering social function [ES =
0.16 (95% CI - 0.52 to 0.19)]. In conclusion, even though limitations must be
considered, evidence shows that BT and spa therapy can significantly improve QoL
of patients with knee OA. Moreover, reduction of drug consumption and improvement
of algofunctional indexes may be other beneficial effects. Further investigation
is needed because of limited available data.
PMID- 29947998
TI - Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis:
a systematic review and meta-analysis of randomized placebo-controlled trials.
AB - Although glucosamine and chondroitin sulfate have showed beneficial effects on
joint tissues in osteoarthritis (OA), their therapeutic use in the clinical
setting is still debatable. Hence, a systematic review and meta-analysis of
randomized placebo-controlled trials was conducted to investigate the efficacy of
glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of
Science, and Google Scholar databases were searched for randomized placebo
controlled trials evaluating the effect of orally administered glucosamine and/or
chondroitin sulfate on OA symptoms using the Western Ontario and McMaster
Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS).
Meta-analysis was conducted using a random-effects model and generic inverse
variance method. Heterogeneity was tested using the I2 statistic index.
Treatments with glucosamine and chondroitin were found to significantly reduce
pain in VAS [weighted mean difference (WMD) - 7.41 mm, 95% CI - 14.31, - 0.51, p
= 0.04 and WMD - 8.35 mm, 95% CI - 11.84, - 4.85, p < 0.00001, respectively].
Their combination did not show this behavior (WMD - 0.28 mm, 95% CI - 8.87, 8.32,
p = 0.95). None of the glucosamine, chondroitin or their combination had a
significant positive effect on the total WOMAC index and its subscores. Oral
supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA.
However, there is no additional effect using both therapeutic agents in
combination for the management of symptomatic knee OA.
PMID- 29948000
TI - Correlation of neurocognitive function and brain lesion load on magnetic
resonance imaging in systemic lupus erythematosus.
AB - Neurocognitive dysfunction and brain injury on magnetic resonance imaging (MRI)
are common in patients with systemic lupus erythematosus (SLE) and are associated
with increased morbidity and mortality. However, brain MRI is expensive, is
restricted by payers, and requires high expertise. Neurocognitive assessment is
an easily available, safe, and inexpensive clinical tool that may select patients
needing brain MRI. In this cross-sectional and controlled study, 76 SLE patients
(69 women, age 37 +/- 12 years) and 26 age and gender-matched healthy subjects
(22 women, age 34 +/- 11 years) underwent assessment of attention, memory,
processing speed, executive function, motor function, and global neurocognitive
function. All subjects underwent brain MRI with T1-weighted, fluid-attenuated
inversion recovery (FLAIR), and diffusion-weighted imaging. Hemispheric and whole
brain lesion load in cm3 were determined using semi-automated methods.
Neurocognitive z-scores in all clinical domains were significantly lower and
whole brain and right and left hemispheres brain lesion load were significantly
greater in patients than in controls (all p <= 0.02). There was significant
correlation between neurocognitive z-scores in all domains and whole brain lesion
load: processing speed (r = - 0.46; p < 0.0001), attention (r = - 0.42; p <
0.001), memory (r = - 0.40; p = 0.0004), executive function (r = - 0.25; p =
0.03), motor function (r = - 0.25; p = 0.05), and global neurocognitive function
(r = - 0.38; p = 0.006). Similar correlations were found for brain hemisphere
lesion loads (all p <= 0.05). These correlations were strengthened when adjusted
for glucocorticoid therapy and SLE disease activity index. Finally, global
neurocognitive z-score and erythrosedimentation rate were the only independent
predictors of whole brain lesion load (both p <= 0.007). Neurocognitive measures
and brain lesion load are worse in SLE patients than in controls. In SLE
patients, neurocognitive z-scores correlate negatively with and independently
predict brain lesion load. Therefore, neurocognitive testing may be an effective
clinical tool to select patients needing brain MRI.
PMID- 29948001
TI - On hepatitis B virus and vasculitis.
PMID- 29948002
TI - Lupus retinopathy: a marker of active systemic lupus erythematosus.
AB - Retinopathy in the context of systemic lupus erythematosus (SLE) is associated
with severe disease and poorer prognosis. We studied retinopathy in our cohort of
Indian lupus patients. Four hundred and thirty-seven patients fulfilling the
Systemic Lupus International Collaborating Clinics-American College of
Rheumatology-2012 criteria, attending the department of Clinical Immunology were
enrolled under this cross-sectional study. A comprehensive clinical (including
ophthalmological) examination and immunological profile were performed.
Retinopathy was defined if cotton-wool spots, haemorrhages, vasculitis, retinal
detachment or optic disc changes as papilledema, optic atrophy were present.
Disease activity was assessed using SLE disease activity index (SLEDAI). Mean age
of participants was 28.06 +/- 9.7 years (93.1% females); median disease duration
12 months (Interquartile range-IQR 6.36). Forty-five (10.3%) had SLE associated
retinopathy. Autoimmune haemolytic anaemia [31.1 vs 14.5%, p value 0.004, odd's
ratio-OR (95% confidence interval-CI) 2.65 (1.33-5.29)], serositis [33.3 vs
18.9%, p value 0.023, OR (CI) 2.14 (1.11-4.10)], lupus nephritis [62.2 vs 40.8%,
p value 0.006, OR (CI) 2.38 (1.26-4.50)], seizures [28.9 vs 12.8%, p value 0.004,
OR (CI) 2.77 (1.36-5.65)] and median SLEDAI score (24 vs 12, p < 0.01) were
significantly higher in those with retinopathy. On adjusted binary logistic
regression, autoimmune hemolytic anemia, lupus nephritis and presence of
antibodies to Smith antigen were predictors for retinopathy. Retinopathy is
common in SLE, a marker of active disease with frequent renal involvement and
should be screened for in all patients with lupus.
PMID- 29948003
TI - Patient-Reported Outcomes of Bleomycin Sclerotherapy for Low-Flow Vascular
Malformations and Predictors of Improvement.
AB - PURPOSE: There is paucity of data on patient-perceived outcomes of bleomycin
sclerotherapy for low-flow vascular malformations. In this study, the long-term
outcomes of bleomycin sclerotherapy were investigated in terms of quality of life
(QoL) and patient-perceived changes in health. MATERIALS AND METHODS: A cohort of
Dutch patients with vascular malformations treated with bleomycin sclerotherapy
(June 2010-November 2015) completed a questionnaire evaluating disease symptoms,
QoL (Short Form 36), patient-perceived change in health status (Global Rating of
Change scales) and treatment satisfaction. QoL was assessed for the patient's
status before and after treatment and was analyzed relative to an age and sex
matched Dutch reference population. Predictive factors associated with QoL and
patient-perceived improvement in overall health status were assessed using
multivariable linear and logistic regression analyses, respectively. RESULTS:
Seventy-seven patients, with a median follow-up of 22 months, were enrolled.
About half of the respondents (49.3%) indicated that they perceived (any form of)
improvement in their overall health status. Most often improved were the specific
health aspects 'pain' (54.5%) and 'overall severity of symptoms' (57.1%). No
factors were significantly predictive for patient-perceived improvement in health
with respect to the vascular malformation. Impairment in work- or study-related
activities prior to sclerotherapy was found to negatively impact physical QoL at
follow-up (p = 0.03). CONCLUSION: Approximately half of patients with low-flow
vascular malformations indicate an improvement in overall health status following
bleomycin sclerotherapy, particularly concerning pain and severity of symptoms.
However, most patients only perceived little to moderate improvement to their
health and desire further treatment.
PMID- 29948004
TI - CT-Guided Microwave Ablation of Liver Tumors in Anatomically Challenging
Locations.
AB - PURPOSE: To assess the feasibility and outcome of microwave ablation (MWA) of
hepatic tumors in anatomically challenging locations. MATERIALS AND METHODS: A
total of 94 patients with 174 hepatic tumors referred for CT-guided MWA were
included in this retrospective institutional review board-approved study. One
hundred and twenty-five tumors (median size 17 mm, range 12-24 mm) with
subcapsular location (n = 91) and/or in which a transpleural approach was applied
(n = 53) were identified (group 1) and compared to tumors with a central
intrahepatic location (group 2; n = 49, median size 19 mm, range 12-23 mm).
Technical success, complications and local tumor progression (LTP) were
evaluated. Risk factors were analyzed using univariate analysis, logistic
regression and Kaplan-Meier curves (p < 0.05 deemed significant). RESULTS:
Technical success was 100% in both groups. In group 1, complications occurred in
n = 31 tumors (24.8%; pneumothorax n = 20; hematoma n = 11). Complications
occurred significantly less often in group 2 (8.2%; n = 4 (hematoma); p = 0.011).
There were no major complications. Transpleural approach and number of capsule
punctures were identified as risk factors for complications (all p < 0.05).
Median follow-up was 265 days. LTP was comparable between both groups (13.6 vs.
10.2%; p = 0.41). Use of hydrodissection was the only independent factor
associated with LTP (p = 0.03, HR 3.29). CONCLUSION: CT-guided hepatic MWA of
subcapsular tumors and subdiaphragmatic tumors requiring a direct or transpleural
approach is feasible with increased minor but not major complications. LTP did
not differ significantly between both groups.
PMID- 29948005
TI - Radioembolization Super Survivors: Extended Survival in Non-operative
Hepatocellular Carcinoma.
AB - PURPOSE: To identify baseline characteristics and long-term prognostic factors in
non-transplant patients with unresectable hepatocellular carcinoma (HCC) who had
prolonged survival after treatment with yttrium-90 radioembolization (Y90).
MATERIALS AND METHODS: Sixty-seven "Super Survivors" (defined as >= 3-year
survival after Y90) were identified within our 1000-patient Y90 database (2003
2017). Baseline imaging and follow-up occurred at 1 month and every 3 months
thereafter. Overall survival (OS) was calculated with Kaplan-Meier estimates with
log-rank test in subgroups: Child-Pugh (CP) score, distribution of disease,
portal vein thrombus (PVT), and technique (segmental vs lobar Y90). RESULTS:
Median age 69.5 years (range 45-94 years); 69% male; 60% solitary HCC; 79%
unilobar disease; 12% PVT; 10% ascites; Barcelona Clinic Liver Cancer Stage A
54%/B-28%/C-16%/D-2%; CP A-70%/B-28%/C-2%. Longest baseline tumor diameter was
5.4 +/- 4.0 cm (mean +/- SD). All patients had an imaging response (either
partial or complete response). Median OS was 67.5 months (95% CI 55.2-82.5). CP
score and main PVT stratified median OS (p = 0.0007 and p = 0.0187,
respectively). Beyond 3 years, segmental versus lobar Y90 was associated with
improved OS with a median OS of 80.2 versus 46.7 months, respectively (p =
0.0024). Dosing > 200 Gy was not a significant predictor of improved OS.
CONCLUSIONS: Super Survivors spanning the BCLC staging system maintained durable
OS after radioembolization that was stratified by the extent of underlying liver
disease. The common variable among all patients was an imaging response.
Segmental versus lobar Y90 may have a long-term associated OS benefit.
PMID- 29948006
TI - Urgent Endovascular Treatment for Non-traumatic Descending Thoracic Aortic
Rupture.
AB - PURPOSE: To evaluate the efficacy of endovascular repair of non-traumatic rupture
of the descending thoracic aorta. MATERIALS AND METHODS: From January 2011 to
August 2017, 22 consecutive patients (16 men, mean age 73.7 years, range 63-92
years) with non-traumatic rupture of the descending thoracic aorta were treated
endovascularly. Thirty-day mortality as well as procedure-related morbidity
including stroke, renal, pulmonary and spinal complications were retrospectively
assessed. Median follow-up was 29 months (range 6-65 months). RESULTS: Nine
patients had type B dissections, and 13 had atherosclerotic aortic aneurysms. The
technical success was 100%; 86.3% of patients (19/22) were treated
percutaneously. Thirteen patients (59%) received a single endograft, 8 (36%)
received 2 endografts, and 1 received 3 endografts. The endograft diameters
ranged between 28 and 46 mm. Two dissection patients received additional distal
bare metal true lumen stents. Eleven patients required additional drainage of
thoracic hematoma. Three primary percutaneous sites (15.7%) required surgical
revision. No spinal cord ischemic or renal complications were observed. Stroke
was observed in 2 patients (9%), both with full coverage of left subclavian
artery origin. Four patients (18%) required tracheostomy with prolonged
respiratory support (range 10-15 days). The median intensive care unit stay was 5
days (range 1-27 days). The 30-day mortality was 18.1% (4/22). CONCLUSION:
Endoluminal repair of non-traumatic rupture of the descending thoracic aorta can
be performed percutaneously. It showed a 30-day mortality of 18.1%, and no spinal
cord injury or renal complications were observed in surviving patients at follow
up. LEVEL OF EVIDENCE: Level 4, case series.
PMID- 29948007
TI - Ethylene production and signaling in tomato (Solanum lycopersicum) pollen grains
is responsive to heat stress conditions.
AB - KEY MESSAGE: Tomato pollen grains have the capacity for ethylene production,
possessing specific components of the ethylene-biosynthesis and -signaling
pathways, being affected/responsive to high-temperature conditions. Exposure of
plants to heat stress (HS) conditions reduces crop yield and quality, mainly due
to sensitivity of pollen grains. Recently, it was demonstrated that ethylene, a
gaseous plant hormone, plays a significant role in tomato pollen heat-tolerance.
It is not clear, however, whether, or to what extent, pollen grains are dependent
on the capacity of the surrounding anther tissues for ethylene synthesis and
signaling, or can synthesize this hormone and possess an active signaling
pathway. The aim of this work was (1) to investigate if isolated, maturing and
mature, tomato pollen grains have the capacity for ethylene production, (2) to
find out whether pollen grains possess an active ethylene-biosynthesis and
signaling pathway and characterize the respective tomato pollen components at the
transcript level, (3) to look into the effect of short-term HS conditions.
Results from accumulation studies showed that pollen, anthers, and flowers
produced ethylene and HS affected differentially ethylene production by
(rehydrated) mature pollen, compared to anthers and flowers, causing elevated
ethylene levels. Furthermore, several ethylene synthesis genes were expressed,
with SlACS3 and SlACS11 standing out as highly HS-induced genes of the pollen
ethylene biosynthesis pathway. Specific components of the ethylene-signaling
pathway as well as several ethylene-responsive factors were expressed in pollen,
with SlETR3 (ethylene receptor; named also NR, for never ripe) and SlCTR2
(constitutive triple response2) being HS responsive. This work shows that tomato
pollen grains have the capacity for ethylene production, possessing active
ethylene-biosynthesis and -signaling pathways, highlighting specific pollen
components that serve as a valuable resource for future research on the role of
ethylene in pollen thermotolerance.
PMID- 29948008
TI - Paenibacillus maysiensis sp. nov., a Nitrogen-Fixing Species Isolated from the
Rhizosphere Soil of Maize.
AB - A novel bacterium SX-49T with nitrogen-fixing capability was isolated from the
rhizosphere soil of maize. Phylogenetic analysis of nifH gene fragment and 16S
rRNA gene sequence revealed that the strain SX-49T is a member of the genus
Paenibacillus. Values of 16S rRNA gene sequence similarity were highest between
SX-49T and P. jamilae DSM 13815T (97.0%), P. brasiliensis DSM 14914T (97.8%), P.
polymyxa DSM 36T (97.5%), and P. terrae DSM 15891T (98.8%). The similarity
between SX-49T and other Paenibacillus species was < 97.0%. DNA-DNA hybridization
values between strain SX-49T and the four type strains were P. jamilae DSM
13815T: 40.6%, P. brasiliensis DSM 14914T: 27.9%, P. polymyxa DSM 36T: 29.2%, and
P. terrae DSM 15891T: 66.4%. The DNA G+C content of SX-49T was 46.4 mol%. The
predominant fatty acids were anteiso-C15:0, C16:0 and iso-C16:0. The predominant
isoprenoid quinone was MK-7. The genome contains 5628 putative protein-coding
sequences (CDS), 6 rRNAs and 56 tRNAs. The phenotypic and genotypic
characteristics, DNA-DNA relatedness, and genome features suggest that SX-49T
represents a novel species of the genus Paenibacillus, and the name Paenibacillus
maysiensis sp. nov. is proposed.
PMID- 29948009
TI - Generation and In Vivo Characterization of Tn5-Induced Biofilm Mutants of Vibrio
cholerae O139.
AB - The Gram-negative bacterium Vibrio cholerae is a unique pathogen with an ability
to colonize human intestine as well as outside environments. The biofilm, an
organized polymeric structure produced by this bacterium known to be a
significant factor for the survival and persistence in hostile conditions.
However, the direct role of biofilm formation by this bacterium in environmental
persistence, in vivo colonization, and pathogenesis remains unexplored. In this
study, we have generated biofilm-altered Tn5 mutants of V. cholerae O139 and
evaluated their in vivo colonization ability on mouse model. These Tn5 mutants
were found to harbor an independent, single Tn5 insertion in their genome. The
DNA sequence analysis revealed that genomic region wherein Tn5 insertion occurred
is identified to be involved in functions like LPS biosynthesis, efflux
transporters, motility, purine metabolism, stringent response, VPS synthesis, and
a hypothetical protein of unknown function. In single-strain infection with the
planktonic culture, the biofilm-altered as well as the biofilm intermediate
mutants were found to be more or less similar in their intestinal colonization
ability, however infection with their biofilm form, a marked difference was
observed between the biofilm deficient and other biofilm forming strains.
Further, in the competition experiments, biofilm deficient and proficient mutants
were found reduced in their colonization ability and outcompeted by their parent
strain. In conclusion, biofilm formation in V. cholerae O139 is a genetically
complex process and the controlled and regulated production of biofilm appeared
to be necessary for its efficient colonization of mouse intestine.
PMID- 29948010
TI - The obturator oblique and iliac oblique/outlet views predict most accurately the
adequate position of an anterior column acetabular screw.
AB - OBJECTIVE: Percutaneous fixation of the acetabulum is a treatment option for
select acetabular fractures. Intra-operative fluoroscopy is required, and despite
various described imaging strategies, it is debatable as to which combination of
fluoroscopic views provides the most accurate and reliable assessment of screw
position. MATERIALS AND METHODS: Using five synthetic pelvic models, an
experimental setup was created in which the anterior acetabular columns were
instrumented with screws in five distinct trajectories. Five fluoroscopic images
were obtained of each model (Pelvic Inlet, Obturator Oblique, Iliac Oblique,
Obturator Oblique/Outlet, and Iliac Oblique/Outlet). The images were presented to
32 pelvic and acetabular orthopaedic surgeons, who were asked to draw two
conclusions regarding screw position: (1) whether the screw was intra-articular
and (2) whether the screw was intraosseous in its distal course through the bony
corridor. RESULTS: In the assessment of screw position relative to the hip joint,
accuracy of surgeon's response ranged from 52% (iliac oblique/outlet) to 88%
(obturator oblique), with surgeon confidence in the interpretation ranging from
60% (pelvic inlet) to 93% (obturator oblique) (P < 0.0001). In the assessment of
intraosseous position of the screw, accuracy of surgeon's response ranged from
40% (obturator oblique/outlet) to 79% (iliac oblique/outlet), with surgeon
confidence in the interpretation ranging from 66% (iliac oblique) to 88% (pelvic
inlet) (P < 0.0001). CONCLUSIONS: The obturator oblique and obturator
oblique/outlet views afforded the most accurate and reliable assessment of
penetration into the hip joint, and intraosseous position of the screw was most
accurately assessed with pelvic inlet and iliac oblique/outlet views. EVIDENCE:
Clinical Question.
PMID- 29948011
TI - Evaluation of three-dimensional in vivo scapular kinematics and scapulohumeral
rhythm between shoulders with a clavicle hook plate and contralateral healthy
shoulders.
AB - PURPOSE: Acromioclavicular-coracoclavicular ligament injury occurs frequently,
and the clavicle hook plate technique is an easy-to-use treatment method.
However, complications such as subacromial impingement syndrome, synovitis,
erosion, osteolysis, post-operative pain, and post-operative limitations in range
of motion have been reported. We aimed to evaluate the use of the clavicle hook
plate in the shoulder joints and to compare in vivo three-dimensional (3D)
scapular kinematics and scapulohumeral rhythm between the shoulders with a
clavicle hook plate and contralateral normal shoulder joints. METHODS: Ten male
patients (aged 40.5 +/- 14.4 years) who underwent clavicle hook plate fixation
for an acromioclavicular-coracoclavicular ligament injury were selected. Computed
tomography and fluoroscopy were conducted on both the shoulder joints, and 3D
models were created. Using a 3D-2D model-image registration technique, we
determined the 3D coordinates of the scapula, and we measured the scapular
kinematics and scapulohumeral rhythm. RESULTS: The values for upward rotation,
posterior tilt, and external rotation in the two groups increased in proportion
with humeral elevation, showing significant differences between the two groups (p
< 0.05). Overall, the value in the clavicle hook plate group (group H) was
smaller than that in the control group (group C) by 23.5% (6.7 degrees ) of
upward rotation and 64.8% (18.9 degrees ) of posterior tilt. However, the
external rotation in group H was greater than that in group C by 32.3% (2.3
degrees ). In overall value, there was a significant difference not in upward
rotation and external rotation, but in posterior tilt. During humeral elevation,
the overall changes in scapulohumeral rhythm were 4.65 +/- 2.45 in group H and
3.8 +/- 0.8 in group C, and statistical differences were not detected between the
two groups. CONCLUSIONS: Clavicle hook plate fixation changes the scapular
kinematics and scapulohumeral rhythm; thus, when clavicle hook plate fixation is
complete, the implant should be promptly removed.
PMID- 29948012
TI - Hallmarks of amputation surgery.
AB - PURPOSE: To highlight the most important innovations and milestones in the
historical evolution of amputation and disarticulation surgery through the ages,
from the early antiquity until the modern era. METHOD: A thorough search of the
literature was undertaken in PubMed and Google Scholar as well as in physical
books in libraries to summarize current and classic literature on the hallmarks
of the history of amputation surgery in the course of medical history. RESULTS:
Amputation of a limb is one of the oldest surgical procedures. Initially, it was
fraught with complications and dismal outcome of the patients because of
hemorrhage and infection. Due to lack of analgesics and narcotics the operation
had to take only a few minutes. Obtaining experience, the surgeons evolved the
operative technique and refined the procedure, anesthesia and perioperative
analgesia was introduced, instruments were developed, and rehabilitation has
enabled functional and social reintegration of amputees. CONCLUSION: From the
Hippocratic era until currently, the surgical approach to amputation has changed
little. However, the indications for amputations have changed a lot and had been
refined, especially in diabetic patients and in those with severe chronic
peripheral vascular disease. An exponential decrease in mortality for an
operation once fraught with complications was due to the development of the
tourniquet, proper vessel ligation and repair, antisepsis, and anesthesia.
PMID- 29948014
TI - Size of greater tuberosity fragment: a risk of iatrogenic injury during shoulder
dislocation reduction.
AB - PURPOSE: Shoulder dislocation with greater tuberosity fractures (GTF) is becoming
increasingly common, as is the number of cases of iatrogenic humeral neck
fractures (IHNF) during reduction. This study investigated the relationship
between size of greater tuberosity fragment and occurrence of IHNF in patients
with shoulder dislocation and GTF. METHODS: A retrospective study was made to
identify all patients presenting with shoulder dislocation with GTF between
September 2014 and July 2016. There were 74 patients with an average age of 52.4
years (range 18-84 years) representing 76 cases of shoulder dislocation
associated with GTF. Patient age, injury mechanism and location, treatment
waiting time, and reduction method were noted. Using conventional anterior
posterior view radiographs, three points were identified as A, B, and C. Distance
ratios between AC and AB were calculated, then the resulting ratio was compared
to a critical value of 0.4. RESULTS: More iatrogenic fractures occurred in cases
where the AC/AB ratio exceeded 0.4. Most (13) occurred during emergency
Hippocratic manual reduction. Only five of 18 iatrogenic fractures (27.78%)
occurred during surgery while under traction. Women ran a higher risk of
iatrogenic fracture than men (female/male ratio 8:1). On average, women were
older than men at the time of fracture (59.75 years for women vs. 42 years for
men). CONCLUSIONS: A statistically significant relationship exists between size
of greater tuberosity fragment and occurrence of iatrogenic humeral neck
fractures during the reduction of shoulder dislocation. The larger the greater
tuberosity fragment, the higher the incidence of iatrogenic humeral neck
fractures. For such fracture dislocations, we recommend open reduction with
internal fixation directly and using a Kirschner wire in advance to reinforce the
proximal humerus before reduction of the shoulder.
PMID- 29948013
TI - Comparison of arthroscopically assisted transfer of the latissimus dorsi with or
without partial cuff repair for irreparable postero-superior rotator cuff tear.
AB - PURPOSE: To evaluate the effect of an additional partial repair in combination
with an arthroscopically assisted transfer of the latissimus dorsi (LDT) in
massive postero-superior irreparable cuff tear. MATERIALS AND METHODS: Thirty-one
patients (mean age 59.2 years) scheduled for arthroscopically assisted LDT either
isolated or in combination with a partial cuff repair for a massive posterior
superior cuff tear were prospectively included between January 2011 and December
2013 at our institution. Seventeen had an isolated transfer (Group A) and 14 had
a transfer combined with a partial cuff repair (Group B). Outcome measures
included visual analogue scale (VAS), range of motion, strength, constant score,
and subjective shoulder value (SSV). Potential predictive factors were analyzed.
RESULTS: At the last follow-up (mean 22 months), patients in Group B had a
significantly higher constant score (64 +/- 8 versus 58 +/- 4 in Group A), range
of motion (33 +/- 5 versus 29 +/- 5 points in Group A), and strength at 90
degrees of abduction (2.5 kg +/- 1 in Group B versus 1.9 kg +/- 0.9 in Group A).
No significant differences were found between both groups regarding pain scores,
SSV, and active external rotation. Thirty-seven variables were analyzed and the
only factor which was found to be predictive of a bad result was a preoperative
SSV < 40 pts. (RR 0.5). CONCLUSION: Arthroscopically assisted LDT gives better
results when combined with a partial repair of the cuff than when it is performed
isolated in the treatment of massive irreparable postero-superior rotator cuff
tear. LEVEL OF EVIDENCE: Treatment study, Level II.
PMID- 29948016
TI - Introduction.
PMID- 29948015
TI - The Legacy Effects of Winter Climate on Microbial Functioning After Snowmelt in a
Subarctic Tundra.
AB - Warming-induced increases in microbial CO2 release in northern tundra may
positively feedback to climate change. However, shifts in microbial extracellular
enzyme activities (EEAs) may alter the impacts of warming over the longer term.
We investigated the in situ effects of 3 years of winter warming in combination
with the in vitro effects of a rapid warming (6 days) on microbial CO2 release
and EEAs in a subarctic tundra heath after snowmelt in spring. Winter warming did
not change microbial CO2 release at ambient (10 degrees C) or at rapidly
increased temperatures, i.e., a warm spell (18 degrees C) but induced changes (P
< 0.1) in the Q10 of microbial respiration and an oxidative EEA. Thus, although
warmer winters may induce legacy effects in microbial temperature acclimation, we
found no evidence for changes in potential carbon mineralization after spring
thaw.
PMID- 29948017
TI - Bacterial and Fungal Midgut Community Dynamics and Transfer Between Mother and
Brood in the Asian Longhorned Beetle (Anoplophora glabripennis), an Invasive
Xylophage.
AB - Microbial symbionts play pivotal roles in the ecology and physiology of insects
feeding in woody plants. Both eukaryotic and bacterial members occur in these
systems where they facilitate digestive and nutrient provisioning. The larval gut
of the Asian longhorned beetle (Anoplophora glabripennis) is associated with a
microbial consortium that fulfills these metabolic roles. While members of the
community vary in presence and abundance among individuals from different hosts,
A. glabripennis is consistently associated with a fungus in the Fusarium solani
species complex (FSSC). We used amplicon sequencing, taxon-specific PCR,
culturing, and imaging to determine how bacterial and fungal communities differ
between life stages and possible modes of symbiont transfer. The bacterial and
fungal communities of adult guts were more diverse than those from larvae and
eggs. The communities of larvae and eggs were more similar to those from
oviposition sites than from adult female guts. FSSC isolates were not detected in
the reproductive tissues of adult females, but were consistently detected on egg
surfaces after oviposition and in frass. These results demonstrate that frass can
serve as a vehicle of transmission of a subset for the beetle gut microbiota.
Vertically transmitted symbionts are often beneficial to their host, warranting
subsequent functional studies.
PMID- 29948018
TI - The Functional Potential of the Rhizospheric Microbiome of an Invasive Tree
Species, Acacia dealbata.
AB - Plant-microbe interactions mediate both the invasiveness of introduced plant
species and the impacts that they have in invaded ecosystems. Although the
phylogenetic composition of the rhizospheric microbiome of Acacia dealbata (an
invasive Australian tree species) has been investigated, little is known about
the functional potential of the constituents of these altered microbial
communities. We used shotgun DNA sequencing to better understand the link between
bacterial community composition and functional capacity in the rhizospheric
microbiomes associated with invasive A. dealbata populations in South Africa. Our
analysis showed that several genes associated with plant growth-promoting (PGP)
traits were significantly overrepresented in the rhizospheric metagenomes
compared to neighbouring bulk soils collected away from A. dealbata stands. The
majority of these genes are involved in the metabolism of nitrogen, carbohydrates
and vitamins, and in various membrane transport systems. Overrepresented genes
were linked to a limited number of bacterial taxa, mostly Bradyrhizobium species,
the preferred N-fixing rhizobial symbiont of Australian acacias. Overall, these
findings suggest that A. dealbata enriches rhizosphere soils with potentially
beneficial microbial taxa, and that members of the genus Bradyrhizobium may play
an integral role in mediating PGP processes that may influence the success of
this invader when colonizing novel environments.
PMID- 29948019
TI - Different Height Forms of Spartina alterniflora Might Select Their Own
Rhizospheric Bacterial Communities in Southern Coast of China.
AB - In the southernmost part of coast of China, two height forms of Spartina
alterniflora, tall and short, have invaded Leizhou Peninsula within the last
decade. However, the effect of different height forms of Spartina alterniflora on
plant-microbe interaction has not been clarified. Here, the community structures
of rhizosphere bacteria and the abundance of N- and S-cycling functional genes
associated with selected S. alterniflora were investigated in the field and a
common garden. The community structure of tall-form S. alterniflora was distinct
from short-form S. alterniflora at OTU level in the field, even after
transplantation into a common garden. The abundance of bacterial amoA, nirS, and
nosZ in tall S. alterniflora was significantly greater than those in short S.
alterniflora in the field; however, this difference disappeared in a 1-year
common garden experiment. These results suggested that compared with the tall
form S. alterniflora, the rhizosphere of short-form S. alterniflora harbored
fewer nitrification-denitrification related microorganisms, which might benefit
from conserving N in an N limited habitat. Together, our results suggested that
tall- and short-form S. alterniflora can host their specific rhizosphere
microbial communities and had different strategies of N usage via selecting the
composition of rhizosphere bacterial assemblages, which in turn might determine
the growth and invasiveness of S. alterniflora in its introduced range.
PMID- 29948020
TI - Extracellular vesicles and ctDNA in lung cancer: biomarker sources and
therapeutic applications.
AB - Lung cancer is the leading cause of cancer death in the world. Recently, targeted
therapy and anti-programmed cell death receptor 1 (PD-1) and anti-programmed cell
death ligand 1 (PD-L1) immunotherapy have made great progress in treatment of
lung cancer. However, responses to these therapies are variable, influenced by
genetic alterations, high microsatellite instability and mismatch repair
deficiency. Liquid biopsy of extracellular vesicles and circulating tumor DNA
(ctDNA) emerges as a new promising non-invasive means that enables not only
biomarker determination, but also continuous monitoring of cancer treatment.
Notably, tumor extracellular vesicles play important roles in tumor formation and
progression, and also serve as natural carriers for anti-tumor drugs and short
interfering RNA. In this review, we summarize the latest progress in
understanding the relationships of extracellular vesicles and ctDNA in cancer
biology, diagnosis and drug delivery. In particular, the application of
extracellular vesicles and ctDNA in anti-PD-1/PD-L1 immunotherapy is discussed.
PMID- 29948021
TI - A pharmacodynamic study of sirolimus and metformin in patients with advanced
solid tumors.
AB - BACKGROUND: Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor.
Metformin may potentiate mTOR inhibition by sirolimus while mitigating its
adverse effects. We conducted a pilot study to test this hypothesis. METHODS:
Patients with advanced solid tumor were treated with sirolimus for 7 days
followed by randomization to either sirolimus with metformin (Arm A) or sirolimus
(Arm B) until day 21. From day 22 onwards, all patients received sirolimus and
metformin. The primary aim was to compare the change in phospho-p70S6K (pp70S6K)
in peripheral blood mononuclear cells (PBMC) from day 8 to day 22 using a two
sample t test. Secondary aims were objective response rate, toxicity, and other
serum pharmacodynamic biomarkers (e.g., fasting glucose, triglycerides, insulin,
C-peptide, IGF-1, IGF-1R, IGF-BP, and leptin). RESULTS: 24 patients were
enrolled, with 18 evaluable for the primary endpoint. There was no significant
difference in mean change in pp70S6K in arm A vs. arm B (- 0.12 vs. - 0.16; P =
0.64). Similarly, there were no significant differences in other serum
pharmacodynamic biomarkers. There were no partial responses. There were no dose
limiting or unexpected toxicities. CONCLUSIONS: Adding metformin to sirolimus,
although well tolerated, was not associated with significant changes in pp70S6K
in PBMC or other serum pharmacodynamic biomarkers. IMPACT: Combining metformin
with sirolimus did not improve mTOR inhibition.
PMID- 29948022
TI - Over-adherence to capecitabine: a potential safety issue in breast and colorectal
cancer patients.
AB - PURPOSE: The aim of the OCTO clinical study was to measure patients' adherence to
capecitabine-based treatment. METHODS: A cohort of ambulatory patients treated
with capecitabine monotherapy for either locally advanced or metastatic, breast
or colorectal cancer was monitored for 6 cycles. Adherence was assessed in all
patients by self-completed questionnaires on disease, pill-count and
pharmacological dosage of FBAL (metabolite of capecitabine); and in half of the
cohort by electronic medication event monitoring systems (MEMSTM) recording the
opening times of the device. RESULTS: Forty patients were enrolled between
November 2008 and September 2011 and treated by capecitabine for an average of
4.75 cycles (range 1-6). Hand-foot syndrome (HFS) was the most frequently
reported toxicity (35% patients), and to a lesser extent fatigue and/or asthenia
(21%), nausea and/or vomiting (13%) and diarrhea (11%). In the MEMSTM cohort, 20
patients were included. Patients' adherence was excellent with very few missing
occasions (23/2272 records). Close analysis of MEMSTM data revealed unexpected
medication patterns, such as patients taking extra days of medication beyond
planned cycle, patients taking extra doses per day and patients missing a day of
dosing and "compensating" by taking extra the following day (N = 7, 18%). A trend
was found between over-adherence and high-grade toxicity (grades 3 and/or 4): OR
4.74 [0.65-45.2], p = 0.13 and higher AUC (p = 0.16). There was a trend towards
increased AUC of FBAL in over-adherent patients (p = 0.16). CONCLUSION: Adherence
to oral anticancer chemotherapy was found excellent in this population suggesting
over-adherence to capecitabine and potential safety implications for outpatients'
drugs.
PMID- 29948023
TI - Pharmacokinetic and pharmacodynamic bioequivalence study of a pegfilgrastim
biosimilar INTP5 in healthy subjects.
AB - PURPOSE: This study compared pharmacokinetics, pharmacodynamics, safety and
immunogenicity profiles of INTP5 (a potential pegfilgrastim biosimilar) with that
of Neulasta(r). METHODS: In this randomised, assessor-blind, crossover study, 344
healthy subjects received single subcutaneous dose of both INTP5 and Neulasta at
3 mg/0.3 ml (n = 172) or 6 mg/0.6 ml (n = 172) dose. The primary endpoints were
AUC0-t, AUC0-infinity and Cmax of pegfilgrastim; and AUEC0-t and Emax of absolute
neutrophil count (ANC). RESULTS: All 344 subjects dosed were included in the
safety and immunogenicity analyses, and 292 subjects in the pharmacokinetic and
pharmacodynamic analyses. At 6 mg dose, test to reference ratio (90% CI) of AUC0
t was 105.65% (99.60-112.06%), AUC0-infinity was 105.72% (99.55-112.28%) and Cmax
was 103.62% (98.19-109.35%); while test to reference ratio (95% CIs) of ANC AUEC0
t was 100.79% (97.75-103.92%) and Emax was 98.70% (95.52-101.98%). Both the
primary endpoints met the bioequivalence criteria (CIs within 80-125%).
Similarly, at 3 mg dose, these endpoints were within the acceptance range of 80
125%. CD34+ profiles were similar and 95% CIs were within acceptance range at
both doses. Adverse events were reported in 54 (15.7%; 8.72% in INTP5 vs. 8.39%
in Neulasta) subjects; most events were mild. The incidences of anti-drug
antibodies were low and similar between INTP5 and Neulasta and no neutralising
antibodies were detected. CONCLUSIONS: Pharmacokinetic and pharmacodynamic
bioequivalence was established between INTP5 and Neulasta following 3 and 6 mg
doses. Safety and immunogenicity profiles were similar between INTP5 and
Neulasta.
PMID- 29948024
TI - Transvenous Versus Epicardial Pacing in Fontan Patients.
AB - Up to 10% of Fontan patients require pacemakers; an epicardial approach has
historically been used. A transvenous approach can be used but carries risk of
Fontan obstruction, thromboembolism, and can be technically challenging. The
safety and efficacy of these approaches is not well described. The aim of this
study was to compare epicardial and transvenous pacemaker outcomes in Fontan
patients, specifically, device performance and adverse event rate. A
retrospective review was performed on Fontan pacemaker patients followed at a
single institution. Thirty-one Fontan pacemaker patients were identified between
1985 and 2017. Twenty-six had an epicardial system, five transvenous, and three
converted from epicardial to transvenous. Average atrial lead sensing at
placement was 3.23 versus 2.35 mV (p = 0.52) for epicardial and transvenous
leads, respectively. Median atrial and ventricular lead longevity was 86.4 versus
98.8 months (p = 0.56) and 73.2 versus 140 months (p = 0.3) with generator
longevity of 65.5 versus 73.9 (p = 0.16) months for epicardial versus transvenous
systems, respectively. One major complication occurred in a transvenous patient,
and two minor complications occurred in epicardial patients. All transvenous
patients received warfarin except one, who converted to dabigatran. Epicardial
patients received aspirin (n = 20), warfarin (n = 3) or a warfarin/aspirin
combination (n = 3). No thromboembolic events occurred. System revision was
required in 13 epicardial and 5 transvenous patients. There were two deaths, none
related to the pacemaker system. Transvenous pacemakers can be utilized with
equal efficacy compared to epicardial pacemakers with trends toward longer lead
longevity in transvenous pacemaker systems.
PMID- 29948026
TI - A Cost-Effective Analysis of Systematically Using Mapping Systems During Catheter
Ablation Procedures in Children and Teenagers.
AB - The aim of this study is to evaluate the cost-effectiveness of an extended use of
3D non-fluoroscopic mapping systems (NMSs) during paediatric catheter ablation
(CA) in an adult EP Lab. This study includes 58 consecutive patients (aged
between 8 and 18) who underwent CA from March 2005 to February 2015. We compare
the fluoroscopy data of two groups: group I, patients who underwent CA from 2005
to 2008 using only fluoroscopy, and group II, patients who underwent CA from 2008
to 2015 performed also using NMSs. Two cost-effectiveness analyses were carried
out: the first method was based on the alpha value (AV), and the second one was
based on the value of a statistical life (VSL). For both methods, a children's
correction factor was also considered. The reduction cost estimated from all
these methods was compared to the real additional cost of using NMSs. The use of
an NMS during a CA procedure has led to an effective dose reduction (DeltaE) of
2.8 milli-Sievert. All presented methods are based on parameters with a wide
range of values. The use of an NMS, applying directly AV values or VSL values, is
not cost-effective for most countries. Only considering the children's correction
factor, the CA procedure using an NMS seems to be cost-effective. The cost
effectiveness of a systematic use of NMSs during CA procedures in children and
teenagers remains a challenging task. A positive result depends on which value of
AV or VSL is considered and if the children's correction factor is applied or
not.
PMID- 29948027
TI - Stent Angioplasty for Critical Native Aortic Coarctation in Three Infants: Up to
15-Year Follow-Up Without Surgical Intervention and Review of the Literature.
AB - Management of neonatal native coarctation is debated till now. Surgical therapy
remains an option but may be unwarranted in critically sick infants with complex
lesions. Balloon dilatation has been employed but with early re-stenosis. Stent
angioplasty has also been used but as a bridge towards definitive surgical
therapy. Four critically sick infants with complex coarctation and additional co
morbidity factors underwent primary stent therapy as surgical intervention was
denied. One patient had died earlier due to reasons unrelated to the procedure.
Three survivors underwent multiple dilatations of primary stents as indicated.
One of the three survivors did not require any further dilatation after the age
of 5 years and remained stable till the time of reporting. High-pressure Cheatham
Platinum stents were implanted inside the primary stents in two infants, who
developed re-stenosis due to somatic growth. These stents were further balloon
dilated at high atmospheric pressure. Femoral arteries in both of them were
blocked but were re-canalized after balloon dilatation in one and stent
angioplasty in the other. After a follow-up of about 15 years, all of them have
been doing fine with acceptable Doppler gradients. They were normotensive and on
no cardiac medications. It can be concluded that, though surgical repair remains
a standard of care, stent angioplasty in selected infants with complex lesions is
feasible and effective. Multiple dilatations can be performed without added risk
of stent migration. Bio-absorbable and growth stents hold a promise for future
use in such situations.
PMID- 29948028
TI - MiRNA-208a as a Sensitive Early Biomarker for the Postoperative Course Following
Congenital Heart Defect Surgery.
AB - Current clinical risk assessment strategies have poor accuracy for identifying
patients who will suffer adverse perioperative events. There is an ongoing need
to integrate clinical variables with novel technology and biomarkers to
accurately predict outcome after pediatric heart surgery. We tested the
hypothesis that miRNAs-208a, -208b, and -499 can serve as noninvasive biomarkers
for the extent of myocardial damage and the postoperative clinical course of
pediatric patients with congenital heart defects (CHDs) at an early time point
following surgery. Serum samples were obtained from 79 pediatric patients before
and 6, 12, and 24 h after surgery. MiRNAs-208a, -208b, and -499 were quantified
by RQ-PCR. Correlations between the patient's clinical variables and miRNA levels
were tested. Our results show that the levels of the three miRNAs were elevated
at 6 h after surgery, remained high at 12 h and declined at 24 h after the
operation. The amount of all three miRNAs at 6 h after surgery correlated with
surgical and laboratory parameters. Their amount at 12 h after surgery correlated
with the length of stay at the hospital. Expression levels of miRNA-208a at 6 h
were related to the appearance of cardiac complications, and could predict
whether a patient will sustain complications or will be ventilated for more than
48 h after surgery. Circulating miRNA-208a is a predictor for the risk of
developing cardiac complications during the postoperative course as early as 6 h
after heart surgery for CHD in pediatric patients.
PMID- 29948029
TI - Systemic Ventricular Dysfunction Between Stage One and Stage Two Palliation.
AB - Infants with a single ventricle can develop systemic ventricular dysfunction
(SVD) after stage 1 operation, but available information is sparse. We reviewed
our patients having Norwood, Sano, or hybrid procedures to better understand this
problem. We conducted a retrospective, case-controlled cohort study of 267
patients having stage1 operation, examining outcomes between stages 1 and 2
(survival and subsequent cardiac surgeries), predictor variables, and histology
of hearts explanted at transplantation. SVD developed in 32 (12%) patients and
resolved in 13 (41%); mean age of onset was 3.0 +/- 1.63 months; median = 2.79.
SVD was not associated with cardiac anatomy, type of stage 1 procedure, weight,
coronary abnormality, or atrioventricular valve regurgitation. The mean age of
resolution = 12.1 +/- 9.6 months; median = 6.3, and resolution may have been more
likely with a systemic LV than RV (p = 0.067). Outcomes for the entire SVD group
were less favorable than for those without, but patients with resolution of SVD
had outcomes at least as good those without SVD. Myocardial histology (n = 4)
suggested chronic ischemia. The risk of SVD after stage 1, while low, may be a
fundamental feature of this patient population. SVD occurs with either a systemic
RV or LV, although patients with a systemic LV may be more likely to have
resolution than those with an RV. We identified no predictor variables, but
histologic findings suggest chronic ischemia may be involved. Given the low
incidence of SVD, multi-center studies will be required to better define
predictors of onset and resolution.
PMID- 29948030
TI - Lipoprotein (a): Examination of Cardiovascular Risk in a Pediatric Referral
Population.
AB - Atherosclerotic cardiovascular disease (CVD), a leading cause of death globally,
has origins in childhood. Major risk factors include family history of premature
CVD, dyslipidemia, diabetes mellitus, and hypertension. Lipoprotein (a) [Lp(a)],
an inherited lipoprotein, is associated with premature CVD, but its impact on
cardiovascular health during childhood is less understood. The objective of the
study was to examine the relationship between Lp(a), family history of premature
CVD, dyslipidemia, and vascular function and structure in a high-risk pediatric
population. This is a single-center, cross-sectional study of 257 children
referred to a preventive cardiology clinic. The independent variable, Lp(a),
separated children into high-Lp(a) [Lp(a) >= 30 mg/dL] and normal-Lp(a) groups
[Lp(a) < 30 mg/dL]. Dependent variables included family history of premature CVD;
dyslipidemia, defined as low-density lipoprotein cholesterol > 130 mg/dL, high
density lipoprotein cholesterol (HDL-C) < 45 mg/dL, triglycerides (TG) > 100
mg/dL; and vascular changes suggesting early atherosclerosis, as measured by
carotid-femoral pulse wave velocity (PWV) and carotid artery intima-media
thickness (CIMT). Of the 257 children, 110 (42.8%) had high Lp(a) and 147 (57.2%)
had normal Lp(a). There was a higher prevalence of African-American children in
the high-Lp(a) group (19.3%) compared to the normal-Lp(a) group (2.1%) (p <
0.001). High Lp(a) was associated with positive family history of premature CVD
(p = 0.03), higher-than-optimal HDL-C (p = 0.02), and lower TG (p < 0.001). There
was no difference in PWV or CIMT between groups. High Lp(a) in children is
associated with family history of premature CVD and is prevalent in African
American children. In children with high Lp(a), promotion of intensive lifestyle
modifications is prudent to decrease premature CVD-related morbidity.
PMID- 29948025
TI - Predictors of Rapid Aortic Root Dilation and Referral for Aortic Surgery in
Marfan Syndrome.
AB - Few data exist regarding predictors of rapid aortic root dilation and referral
for aortic surgery in Marfan syndrome (MFS). To identify independent predictors
of the rate of aortic root (AoR) dilation and referral for aortic surgery, we
investigated the data from the Pediatric Heart Network randomized trial of
atenolol versus losartan in young patients with MFS. Data were analyzed from the
echocardiograms at 0, 12, 24, and 36 months read in the core laboratory of 608
trial subjects, aged 6 months to 25 years, who met original Ghent criteria and
had an AoR z-score (AoRz) > 3. Repeated measures linear and logistic regressions
were used to determine multivariable predictors of AoR dilation. Receiver
operator characteristic curves were used to determine cut-points in AoR dilation
predicting referral for aortic surgery. Multivariable analysis showed rapid AoR
dilation as defined by change in AoRz/year > 90th percentile was associated with
older age, higher sinotubular junction z-score, and atenolol use (R2 = 0.01) or
by change in AoR diameter (AoRd)/year > 90th percentile with higher sinotubular
junction z-score and non-white race (R2 = 0.02). Referral for aortic root surgery
was associated with higher AoRd, higher ascending aorta z-score, and higher
sinotubular junction diameter:ascending aorta diameter ratio (R2 = 0.17). Change
in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change
in AoRd of 0.34 cm/year had 38% sensitivity and 95% specificity for predicting
referral for aortic surgery. In this cohort of young patients with MFS, no new
robust predictors of rapid AoR dilation or referral for aortic root surgery were
identified. Further investigation may determine whether generalized proximal
aortic dilation and effacement of the sinotubular junction will allow for better
risk stratification. Rate of AoR dilation cut-points had high specificity, but
low sensitivity for predicting referral for aortic surgery, limiting their
clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364.
PMID- 29948032
TI - Longitudinal Outcomes of Epicardial and Endocardial Pacemaker Leads in the Adult
Fontan Patient.
AB - Placement of an epicardial pacemaker system is often preferred over an
endocardial system in patients who have undergone a Fontan operation, but data
are limited on how these two systems perform over time in patients with Fontan
palliation. We performed a retrospective review of adults with Fontan palliation
who had pacemaker implantation and interrogation data at Mayo Clinic from 1994 to
2014. Lead parameters, pacing mode, and polarity were collected at the earliest
device interrogation report. Clinic notes and device interrogation reports were
reviewed at implantation, 6 months, and yearly after implantation to determine
impedance, capture threshold (CT), and energy threshold (ET). There were 87
patients with 168 leads in the study cohort. The mean follow-up time was 7.7
years (6 months-19 years). There were 143 epicardial leads (57 atrial and 86
ventricular) and 25 endocardial leads (20 atrial and 5 ventricular). There was no
difference in the baseline lead parameters between epicardial and endocardial
leads for impedance (610 +/- 259 versus 583 +/- 156 Omega, p = 0.93), CT (2.0 +/-
1.3 versus 1.8 +/- 1.3 V, p = 0.28), or ET (7.1 +/- 12.5 versus 6.8 +/- 18.1 uJ,
p = 0.29). Compared to endocardial leads, ventricular epicardial leads were
associated with temporal decrease in impedance and increase in ET. Regarding
clinical outcomes, epicardial leads had higher rates of failure but similar
generator longevity in comparison to endocardial leads. Ventricular epicardial
leads were associated with temporal decrease in impedance and increase in ET.
Epicardial leads had a higher rate of failure but similar generator longevity
compared to endocardial leads.
PMID- 29948031
TI - Bradyarrhythmias in Repaired Atrioventricular Septal Defects: Single-Center
Experience Based on 34 Years of Follow-Up of 522 Patients.
AB - Atrioventricular Septal Defect (AVSD) is a rare congenital heart defect (CHD)
often associated with genetic syndromes, most commonly Down syndrome (DS). Over
the last four decades, surgical repair has increased survival and improved
quality of life in these patients. The prevalence of bradyarrhythmias namely,
atrioventricular block (AVB) and sinus node dysfunction (SND) in AVSD is
partially known. 522 cases with both partial and complete AVSD (38.7% with DS),
undergoing intracardiac repair from 1982 to 2016 at our institution, were
reviewed from our system database. 38 (7.3%) patients received permanent PM
implantation for AVB (early or late) or SND. On one hand, AVB requiring PM was
found in 26 (4.98%). This was further subdivided into early-onset 14 (2.6%) and
late-onset AVB 12 (2.2%) (median 4 [IQR 1-7] years). On the other hand, 12 (2.3%)
experienced late SND requiring PM (median 11 [IQR 3.5-15.2] years). Early and
late AVB were independent from the type of AVSD (partial or complete), whereas
the late SND was remarkably observed in complete AVSD compared to partial AVSD (p
= 0.017). We classified the cohort into two main categories: DS (202, 38.7%) and
non-DS (320, 61.3%). At Kaplan-Meier survival analysis, DS was significantly
associated with late-onset bradyarrhythmias (p = 0.024). At Cox regression
analysis, we identified DS as an independent predictor of PM implantation (HR
2.17). In conclusion, about 7% of repaired AVSD patients need PM implantation
during follow-up. There are no differences in early and late AVB occurrence
according to the type of AVSD. There is a higher incidence of late SND in
repaired complete AVSD, with a later timing onset in patients with associated DS.
Moreover, DS seems to be an independent predictor of PM implantation.
PMID- 29948033
TI - Elevated Pulmonary Artery Pressure, Not Pulmonary Vascular Resistance, is an
Independent Predictor of Short-Term Morbidity Following Bidirectional
Cavopulmonary Connection.
AB - Single ventricle palliation relies on the pulmonary vasculature accommodating non
pulsatile systemic venous return. Mean pulmonary artery pressure (MPAP) and
indexed pulmonary vascular resistance (PVRi) are two measures that impact
pulmonary blood flow following bidirectional cavopulmonary connection (BCPC). The
purpose of the study was to determine which hemodynamic features are associated
with adverse outcomes after BCPC. Pre-operative hemodynamic data and post
operative morbidity and mortality in 250 patients undergoing BCPC at a single
center from 2008 to 2014 were reviewed. Patients were then separated into 5
physiologic states based on MPAP, PVRi, and degree of pulmonary to systemic blood
flow (Qp:Qs). There were 9 (3.6%) deaths, and 49 patients (20%) sustained major
morbidity. An ROC curve identified MPAP > 16 mmHg as an inflection point. Pre
BCPC sildenafil and oxygen use, ventricular dysfunction, and MPAP > 16 mmHg (OR
4.1 [95% CI 1.8-9.2]) were independently associated with morbidity. MPAP > 16
mmHg (OR 6.7 [95% CI 1.6-28]) and pre-BCPC oxygen use were associated with
hospital mortality. PVRi was not associated with morbidity or mortality. Of the
five physiologic states, patients with high MPAP, low PVRi, and low Qp:Qs fared
the worst, with the highest risk of major morbidity (OR 8.6 [3.0-24.9]) and
highest risk of mortality (OR 8.0 [1.5-41.3]) when compared to their reference
groups (low MPAP, low PVRi). Elevated MPAP, need for pre-operative oxygen
support, sildenafil use, and systemic ventricular systolic dysfunction predict
morbidity following BCPC. Specifically, patients with elevated MPAP not due to
elevated PVRi or pulmonary blood flow had the highest risk of morbidity and
mortality.
PMID- 29948034
TI - Does Prophylactic Ibuprofen After Surgical Atrial Septal Defect Repair Decrease
the Rate of Post-Pericardiotomy Syndrome?
AB - Post-pericardiotomy syndrome (PPS) is an inflammatory process involving the
pleura, pericardium, or both and occurs after cardiothoracic surgery. Surgical
atrial septal defect (ASD) closure is associated with higher incidence of PPS
post-operatively as compared to other operations. Reported incidence of PPS
varies from 1 to 40%. NSAIDs are often used to treat PPS and in our center, some
practitioners have prescribed ibuprofen prophylactically. This study sought to
investigate the impact of prophylactic treatment with ibuprofen on the
development and severity of PPS following surgical ASD closure, with particular
attention to secundum-type ASDs. We retrospectively reviewed clinical and
operative data of all surgical ASD repairs in our center from 1/2007 to 7/2017.
ASDs were grouped by subtype. PPS was considered positive if the primary
cardiologist diagnosed and documented clinical signs of PPS on post-operative
outpatient follow-up. Records were reviewed to confirm documented diagnosis of
PPS. A total of 245 cases were reviewed with 207 having sufficient data. Median
age was 2 years (range 4 months-27 years), female 57%. Overall incidence of PPS
was 10%. There was no difference in incidence of PPS in those prescribed
ibuprofen as compared to those who were not. This was true for both the entire
cohort and the subgroup analysis (P = 1.0). Four patients overall required
pericardiocentesis, none of whom received prophylactic ibuprofen. Prophylactic
ibuprofen prescription following surgical ASD repair did not reduce the rate of
PPS in our cohort.
PMID- 29948035
TI - Quantification of fat content in lipid-rich myxoid liposarcomas with MRI: a
single-center experience with survival analysis.
AB - OBJECTIVE: To determine the fat content of myxoid liposarcomas (MLS) on MRI and
to identify any association between lipid content and survival. MATERIALS AND
METHODS: The fat percentage of MLS diagnosed between January 2006 and December
2016 at a single institution was assessed by two radiologists on preoperative MR
images. A Cox proportional hazard model was used to determine any association
between tumor fat percentage and survival time. Tumor fat percentage was the
single predictor in the model. A significance level of 0.05 was used. The Kaplan
Meier estimator was also used to provide a nonparametric estimate of the survivor
function within the entire sample and within two patient subgroups consists of
lipid-rich and lipid-poor tumors. Lipid-rich tumors were defined as any tumors
showing more than 20% of fat on MRI. A 20% cutoff was determined arbitrarily.
RESULTS: Of the 43 cases identified through retrospective review, 8 tumors
demonstrated >=10% fat on MRI, and 4 tumors demonstrated >=20% fat (highest fat
percentage, 38%). There was no significant survival difference between patients
with high tumor fat, which was defined as >=20% fat, compared with those with
little to no tumor fat. CONCLUSION: Myxoid liposarcomas may demonstrate a higher
fat content on MRI than has previously been reported in the literature. Increased
tumor fat percentage in lipid-rich tumors was not found to be associated with
increased risk of death. Radiologists must be aware of the existence of MLS
lesions with higher fat content.
PMID- 29948036
TI - A prototype assembled 3D-printed phantom of the glenohumeral joint for
fluoroscopic-guided shoulder arthrography.
AB - PURPOSE: To describe the methodology of constructing a three-dimensional (3D)
printed model of the glenohumeral joint, to serve as an interventional phantom
for fluoroscopy-guided shoulder arthrography training. MATERIALS AND METHODS: The
osseous structures, intra-articular space and skin surface of the shoulder were
digitally extracted as separate 3D meshes from a normal CT arthrogram of the
shoulder, using commercially available software. The osseous structures were 3D
printed in gypsum, a fluoroscopically radiopaque mineral, using binder jet
technology. The joint capsule was 3D printed with rubber-like TangoPlus material,
using PolyJet technology. The capsule was secured to the humeral head and glenoid
to create a sealed intra-articular space. A polyamide mold of the skin was
printed using selective laser sintering. The joint was stabilized inside the
mold, and the surrounding soft tissues were cast in silicone of varying
densities. Fluoroscopically-guided shoulder arthrography was performed using
anterior, posterior, and rotator interval approaches. CT arthrographic imaging of
the phantom was also performed. RESULTS: A life-size phantom of the glenohumeral
joint was constructed. The radiopaque osseous structures replicated in-vivo
osseous corticomedullary differentiation, with dense cortical bone and less dense
medullary cancellous bone. The glenoid labrum was successfully integrated into
the printed capsule, and visualized on CT arthrography. The phantom was
repeatedly used to perform shoulder arthrography using all three conventional
approaches, and simulated the in vivo challenges of needle guidance. CONCLUSIONS:
3D printing of a complex capsule, such as the glenohumeral joint, is possible
with this technique. Such a model can serve as a valuable training tool.
PMID- 29948037
TI - Effects of post-fracture non-weight-bearing immobilization on muscle atrophy,
intramuscular and intermuscular adipose tissues in the thigh and calf.
AB - OBJECTIVE: Disuse and/or a non-weight-bearing condition changes muscle
composition, with decreased skeletal muscle tissue and increased fat within
(intramuscular adipose tissue, IntraMAT) and between (intermuscular adipose
tissue, InterMAT) given muscles. Excessive adipose tissue contributes to
dysfunctional and metabolically impaired muscle. How these adipose tissues change
during orthopedic treatment (e.g., cast immobilization, daily use of crutches) is
not well documented. This study aimed to quantify changes in IntraMAT, InterMAT,
and thigh and calf muscle tissue during orthopedic treatment. MATERIALS AND
METHODS: We studied 8 patients with fifth metatarsal bone or fibular fractures.
The ankle joint involved underwent plaster casting for approximately 4 weeks,
with crutches used during that time. Axial T1-weighted MRI at the mid-thigh and a
30% proximal site at the calf were obtained to measure IntraMAT and InterMAT
cross-sectional areas (CSAs) and skeletal muscle tissue CSA before treatment and
4 weeks afterward. RESULTS: Thigh and calf muscle tissue CSAs were significantly
decreased from before to after treatment: thigh, 85.8 +/- 7.6 to 77.1 +/- 7.3
cm2; calf, 53.3 +/- 5.5 to 48.9 +/- 5.0 cm2 (p < 0.05). None of the IntraMAT or
InterMAT changes was statistically significant. There was a relation between the
percentage change of thigh IntraMAT CSA and muscle tissue CSA (rs = -0.86, p <
0.01). CONCLUSIONS: The 4 weeks of treatment primarily induced skeletal muscle
atrophy with less of an effect on IntraMAT or InterMAT. There is a risk of
increasing IntraMAT relatively by decreasing skeletal muscle tissue size during
orthopedic treatment.
PMID- 29948038
TI - Case report: Broad insertion of a large subscapularis tendon in association with
congenital absence of the long head of the biceps tendon.
AB - Congenital absence of the long head of the biceps (LHB) tendon is a rare
variation in shoulder anatomy. The authors present a case of congenital absence
of the long head of the biceps tendon associated with a large insertion of the
subscapularis muscle. The patient initially presented with shoulder pain on
overhead activity. Shoulder examination was negative for signs of a torn biceps
tendon. MRI revealed congenital absence of the LHB tendon, a rim rent tear of the
supraspinatus, and a large insertion of the subscapularis muscle. This is the
first reported case describing a large insertion of the subscapularis muscle
associated with absence of the LHB tendon.5.
PMID- 29948039
TI - Modified technique for imaging the wrist and elbow in obese and claustrophobic
patients using a non-open standard MRI scanner.
AB - OBJECTIVE: It is challenging to image extremely obese and claustrophobic patients
using a standard, non-open, magnetic resonance imaging (MRI) scanner. On the
other hand, installing an additional upright or open MRI scanner may not be cost
effective for most practices. Our technique with a patient in a sitting or
standing position behind the standard MRI scanner may be helpful in the MR
examination of the wrist/elbow in these patients using a standard wrist/elbow
coil. MATERIAL AND METHODS: We performed wrist and elbow MRI of extremely obese
and claustrophobic patients by using our modified technique with the patient
sitting or standing outside the standard non-open MRI scanner. A total number of
20 cases with the following diagnosis were examined: triquetral and scaphoid bone
contusions and fractures, scapholunate ligament tears, triangular fibrocartilage
complex tear, and biceps tear. RESULTS: Comparison of image quality for
diagnostic information between the standard technique and our technique showed no
significant difference, which is necessary for making the diagnosis. CONCLUSIONS:
Our technique enables wrist and elbow imaging of extremely obese and
claustrophobic patients who cannot otherwise be imaged using a standard MRI
scanner without compromising the image quality that is essential for making a
diagnosis.
PMID- 29948040
TI - Ultrasonography could be used to predict extended insertion of the EPB tendon
noninvasively.
AB - INTRODUCTION: An abnormal distal insertion of the extensor pollicis brevis (EPB)
tendon into the thumb interphalangeal joint (IP) has been observed in refractory
cases of de Quervain's disease. This is associated with the extensor being wider
at the midpoint of the proximal phalanx; however, there is no method to
noninvasively measure this. This study evaluated the accuracy of measuring the
extensor width using ultrasonography, to establish a noninvasive method for
predicting an EPB extending the IP insertion. MATERIALS AND METHODS: Of 23 arms
from 12 fresh frozen cadavers, the extensor tendon width at the midpoint of the
proximal phalanx was measured using ultrasonography and directly at dissection.
The association between these values was evaluated using correlation analysis. A
cut-off value of extensor tendon width was obtained using receiver operating
characteristic analysis. RESULTS: A strong correlation was observed between the
ultrasonography and the measured values. The EPB tendons were normal in 13 arms
(57%) and extended in 10 (43%), with a significant difference between these
groups in the mean width of the extensor tendon (6.8 +/- 1.1 vs. 8.4 +/- 1.0 mm).
A cut-off extensor tendon width of 8.0 mm yielded an EPB extending the IP.
CONCLUSION: An EPB extending the IP tendon can be predicted by measuring the
extensor tendon width at the midpoint of the proximal phalanx using
ultrasonography. The cut-off tendon width value of >= 8.0 mm may be useful for
assessments prior to surgery and for conservative care.
PMID- 29948042
TI - Functional follow-up after Advance(r) and Advance XP(r) male sling surgery:
assessment of predictive factors.
AB - PURPOSE: To evaluate the efficacy of the Advance(r) and AdvanceXP(r) slings in
men with stress urinary incontinence (SUI) post-radical prostatectomy and to
identify predictive factors for outcome. METHODS: Included were male patients
with SUI following radical prostatectomy who had a positive "repositioning test",
24 h-pad weight (PW) test < 400 g and who were continent at night and at rest.
Urgency was defined as a sudden compelling desire to pass urine, which was
difficult to defer. The cure rate was defined as no pad use. RESULTS: From
February 2008 to October 2014, 24 AdVance(r) and 70 AdVance XP(r) were implanted.
The median (range) follow-up was 49 (12-102) months. The overall cure rate was
77%. The preoperative 24 h PW was significantly related to the continence outcome
(p = 0.044). A total of 12 patients (13%) presented with postoperative AUR, which
was significantly related to abnormal voiding detrusor activity (p = 0.036).
Twenty-two patients (23%) had postoperative urgency (16% "de novo"), which was
significantly related to preoperative urgency (p = 0.003). During follow-up, a
degree of deterioration of continence was observed in five patients who were
classed as cured initially. To date, no reports of urethral sling erosion have
been made. CONCLUSIONS: The AdVance(r) and AdVanceXP(r) slings are safe and
effective in relieving SUI following post-radical prostatectomy. There were no
differences between the two slings in terms of efficacy, urgency or postoperative
AUR. There was a moderate rate of "de novo "urgency and low rate of loss of
continence during follow-up.
PMID- 29948041
TI - Friar Leopold Mandic (1866-1942): the computed tomography of the body of a saint.
AB - PURPOSE: In forensic clinical anatomy computed tomography (CT) is used in post
mortem radiological investigation as an objective nondestructive documentation of
the body surface and of the interior of the body. This technique is applied also
in paleopathology, in particular in mummy studies, with the aim of providing a
permanent record of the mummy's features, investigating the embalming procedure
employed and analyzing the extent of the preservation in detail. METHODS: For the
Extraordinary Jubilee of Mercy, the mortal remains of Saint Leopold Mandic and
Saint Pio da Pietralcina, as examples of Mercy known by everyone, have been
brought to Rome in February 2016. During the survey that preceded the preparation
for transport to Rome, a whole-body CT was performed on the mummified corpse of
Leopold Mandic, Capuchin Saint of Padova, Italy. RESULTS: The CT examination
demonstrated the presence of osteoarthritis at the level of the vertebral column,
of the left knee and of the left hand. Moreover, CT showed the preservation of
skeleton and partial preservation of the some viscera, such as remnants of the
brain, heart, oesophagus, urinary bladder, plexuses and spinal nerves, ear
ossicles, major arterial vessels (aorta and carotid arteries). It is to emphasize
the fact that Saint Leopold was not subjected before the CT to any conservative
treatment. CONCLUSIONS: Computed tomography demonstrated to be a non-destructive
method to investigate Saint Leopold, in order to maintain the integrity of the
body and to acquire data on his pathologies and on his preservation. CT allows
not only the acquisition of sectional images but also, thanks to dedicated
software, the post-processing and reconstruction of three-dimensional models,
that can be used also for public displays.
PMID- 29948043
TI - Molecularly-driven precision medicine for advanced bladder cancer.
AB - Urothelial carcinoma of the bladder is a heterogeneous disease with many
challenges for clinicians and patients alike. However, for the most part of the
last three decades, treatment and outcomes for patients with this disease have
not changed a lot. With recent advances in immunooncology leading to the approval
of multiple agents for the metastatic setting, the treatment landscape started to
change. With the emergent data from landmark multi-institutional sequencing
projects as well as molecular data from recent trials, our understanding of the
underlying disease biology, response patterns as well as definition of molecular
subtypes has evolved tremendously. This review aims to summarize the currently
available concepts of mutational profiles and molecular subtypes as well as their
implications for management of urothelial carcinoma.
PMID- 29948044
TI - Impact of multiparametric MRI and MRI-targeted biopsy on pre-therapeutic risk
assessment in prostate cancer patients candidate for radical prostatectomy.
AB - PURPOSE: To assess the current status and future potential of multiparametric MRI
(mpMRI) and MRI-targeted biopsy (MRI-TBx) on the pretherapeutic risk assessment
in prostate cancer patients' candidates for radical prostatectomy. METHODS: A
literature search of the MEDLINE/PubMed and Scopus database was performed.
English-language original and review articles were analyzed and summarized after
an interactive peer-review process of the panel. RESULTS: Pretherapeutic risk
assessment tools should be based on target plus systematic biopsies, where the
addition of systematic biopsy (TRUS-Bx) to the mpMRI-target cores is associated
with a lower rate of upgrading at final pathology. The combination of mpMRI
findings with clinical parameters outperforms models based on clinical parameters
alone in the prediction of adverse pathological outcomes and oncological results.
This is particularly true when a specialized radiologist is present. CONCLUSION:
The combination of mpMRI findings and clinical parameters should be considered to
improve patient stratification in the pretherapeutic risk assessment. There is an
urgent need to develop or include MRI data and MRI-TBx findings in available
preoperative risk tools. This will allow improving the pretherapeutic risk
assessment, providing important additional information for patient-tailored
treatment planning and optimizing outcomes.
PMID- 29948045
TI - Surveillance after prostate focal therapy.
AB - INTRODUCTION: Long-term outcomes from large cohorts are not yet available upon
which to base recommended follow-up protocols after prostate focal therapy. This
is an updated summary of a 2015 SIU-ICUD review of the best available current
evidence and expert consensus on guidelines for surveillance after prostate focal
therapy. METHODS: We performed a systematic search of the PubMed, Cochrane and
Embase databases to identify studies where primary prostate focal therapy was
performed to treat prostate cancer. RESULTS: Multiparametric magnetic resonance
imaging (mpMRI) should be performed at 3-6 months, 12-24 months and at 5 years
after focal therapy. Targeted biopsy of the treated zone should be performed at 3
6 months and fusion biopsy of any suspicious lesion seen on mpMRI. Additionally,
a systematic biopsy should be performed at 12-24 months and again at 5 years. In
histological diagnosis, characteristic changes of each treatment modality should
be noted and in indeterminate situations various immunohistochemical molecular
markers can be helpful. Small volume 3 + 3 (Prognostic grade group [PGG] 1) or
very small volume (< 0.2 cc or < 7 mm diameter) 3 + 4 (PGG 2) are acceptable in
the treated zone at longitudinal follow-up. Significant volumes of 3 + 4 (PGG 2)
or more within the treated zone should be treated. Any clinically significant
cancer subsequently arising within the non-treated zone should be treated and
handled in the same way as any de novo prostate cancer. Patients should be
counseled regarding whole-gland and focal approaches to treating these new foci
where appropriate. One or two well-delineated foci of significant cancer can be
ablated to keep the patient in the 'active surveillance pool'. More extensive
disease should be treated with traditional whole-gland techniques. CONCLUSION:
Focal therapy remains a nascent field largely comprising single center cohorts
with little long-term data. Our current post-focal therapy surveillance consensus
recommendations represent the synthesis of the best available evidence as well as
expert opinion. Further work is necessary to define the most oncologically safe
and cost-effective way of following patients after focal therapy.
PMID- 29948047
TI - Alpha-blockers with or without phosphodiesterase type 5 inhibitor for treatment
of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a
systematic review and meta-analysis.
AB - PURPOSE: Recently, several randomized controlled trials (RCTs) explored the
effects of alpha-blockers with or without phosphodiesterase type 5 inhibitors
(PDE5-Is) for lower urinary tract symptoms secondary to benign prostatic
hyperplasia (LUTS/BPH). However, the results were inconsistent. We performed this
meta-analysis to evaluate the role of combination therapy (alpha-blockers and
PDE5-Is) in patients with LUTS/BPH. MATERIALS AND METHODS: Databases including
PubMed, Cochrane library, Web of Science, and Embase were searched for qualified
RCTs. Pooled mean differences (MDs) and odds ratios (ORs) were calculated to
measure the effects and adverse events in combination therapy. Moreover, subgroup
analyses of ethnicity, dosage of PDE5-Is, treatment duration, and severity of
LUTS/BPH were performed. In addition, trial sequential analyses (TSAs) were used
to assess whether the evidence for the results was sufficient. RESULTS: Overall,
this study identified 11 eligible RCTs, including 855 LUTS/BPH patients. Patients
receiving combination therapy had better improvement in international prostate
symptom score (IPSS: MD: 1.66, 95% CI - 3.03 to - 0.29), maximum urinary flow
rate (Qmax: MD: 0.94, 95% CI 0.24-1.64), and international index of erectile
function (IIEF: MD: 4.73, 95% CI 2.95-6.51), comparing those without PDE5-Is.
Besides, subgroup analyses indicated that the effects of combination treatment
were associated with ethnicity, treatment duration, and severity of LUTS/BPH. By
TSA, the findings in the current study were based on sufficient evidence.
CONCLUSIONS: Our results indicated that combination therapy can significantly
improve IPSS, Qmax, and IIEF in patients with LUTS/BPH. Combination therapy might
be more suitable for these patients.
PMID- 29948046
TI - Early urological care of patients with spinal cord injury.
AB - PURPOSE: After spinal cord injury (SCI), the initial goals of urological
management include maintaining safe storage of urine with efficient bladder
emptying, maximising urinary continence, and minimising the risk of urological
complications. METHODS: This review was performed according to the methodology
recommended by the Joint SIU-ICUD International Consultation. Embase and Medline
databases were used to identify literature relevant to the early urological care
of SCI patients. Recommendations were developed by consensus and graded using a
modified Oxford system which identifies level of evidence (LOE) and grade of
recommendation (GOR). RESULTS: Clinicians must ensure appropriate bladder
emptying immediately after SCI (LOE 3, GOR A) and perform the initial neuro
urological assessment within 3 months after injury (LOE 3, GOR A), including
history, validated questionnaires, bladder diary, physical examination,
measurement of renal function, and urinary tract imaging (LOE 4, GOR B).
Urodynamics, if available video-urodynamics, must be performed to detect and
specify lower urinary tract dysfunction (LOE 1, GOR A). Spontaneous voiding
and/or intermittent catheterization must be considered in appropriate patients
once they are medically stable (LOE 3, GOR A). Antimuscarinics are the first-line
and intradetrusor botulinum toxin A injections are the second-line treatment for
neurogenic detrusor overactivity (LOE 1, GOR A). Irreversible surgical
interventions should be delayed until the second year after injury due to the
potential for neurological recovery (LOE 4, GOR B). CONCLUSIONS: Careful clinical
assessment and pertinent urological testing including urodynamic investigation
are necessary for appropriate counselling and treatment of new SCI patients.
PMID- 29948048
TI - Imaging for the diagnosis and response assessment of renal tumours.
AB - PURPOSE: Imaging plays a key role throughout the renal cell carcinoma (RCC)
patient pathway, from diagnosis and staging of the disease, to the assessment of
response to therapy. This review aims to summarise current knowledge with regard
to imaging in the RCC patient pathway, highlighting recent advances and
challenges. METHODS: A literature review was performed using Medline. Particular
focus was paid to RCC imaging in the diagnosis, staging and response assessment
following therapy. RESULTS: Characterisation of small renal masses (SRM) remains
a diagnostic conundrum. Contrast-enhanced ultrasound (CEUS) has been increasingly
applied in this field, as have emerging technologies such as multiparametric MRI,
radiomics and molecular imaging with 99mtechnetium-sestamibi single photon
emission computed tomography/CT. CT remains the first-line modality for staging
of locoregional and suspected metastatic disease. Although the staging accuracy
of CT is good, limitations in determining nodal status persist. Response
assessment following ablative therapies remains challenging, as reduction in
tumour size may not occur. The pattern of enhancement on CT may be a more
reliable indicator of treatment success. CEUS may also have a role in monitoring
response following ablation. Response assessments following anti-angiogenic and
immunotherapies in advanced RCC is an evolving field, with a number of
alternative response criteria being proposed. Tumour response patterns may vary
between different immunotherapy agents and tumour types; thus, future response
criteria modifications may be inevitable. CONCLUSION: The diagnosis and
characterisation of SRM and response assessment following targeted therapy for
advanced RCC are key challenges which warrant further research.
PMID- 29948049
TI - Modeling human bladder cancer.
AB - INTRODUCTION: Bladder cancer is a major public health concern and the treatment
options available are unable to significantly prevent disease recurrence and
progression. The need for experimental tumor models to efficiently reproduce the
pathology of human cancers has prompted researchers to attempt various
approaches. METHODS: A PubMed search combining the MeSH bladder cancer and models
was executed in March 2017. RESULTS: We review the advantages and limitations of
currently available in vitro 2D and 3D bladder cancer models as well as in vivo
rodent models. To date, despite the description of a variety of animal models
(including transplantable, carcinogen-induced and genetically engineered models),
the establishment of reliable, simple, practicable and reproducible animal models
remains an ongoing challenge. Recently, sophisticated 3D culture systems have
been designed to better recapitulate the phenotypic and cellular heterogeneity as
well as microenvironmental aspects of in vivo tumor growth, while being more
flexible to conduct repeated experiments. CONCLUSION: Selecting the most
appropriate model for a specific application will maximize the conversion of
potential therapies from the laboratory to clinical practice and requires an
understanding of the various models available.
PMID- 29948050
TI - Characterizing trends in treatment modalities for localized muscle-invasive
bladder cancer in the pre-immunotherapy era.
AB - INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is an aggressive disease for
which treatment strategies are continuously evolving. We characterized trends in
treatment modalities for MIBC from 2004 to 2013 (the "pre-immunotherapy era") and
identified predictors of receiving the current standard of care treatment:
neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). METHODS: We
used the National Cancer Database to identify individuals diagnosed with
clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence
of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy
and/or radiation alone, and no treatment. We then identified factors associated
with receiving NAC prior to RC. RESULTS: There was a notable increase in the use
of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013
(P < 0.001). Factors associated with decreased odds of receiving this regimen
included being older, Black, uninsured, less educated, and more burdened by
comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone
remained relatively constant (approximately 5 and 17%, respectively). There was a
consistent decline in the proportion of patients who did not receive any
treatment, down to 34.20% in 2013. CONCLUSION: Trends in localized MIBC treatment
have evolved substantially since the early 2000s, and certain patient
characteristics are associated with lower odds of receiving the current standard
of care. This serves as a foundation from which to judge the impact of the
upcoming immunotherapy era on the treatment landscape for this disease.
PMID- 29948052
TI - Crocodile-jaw sign.
PMID- 29948051
TI - Fertility and sexuality in the spinal cord injury patient.
AB - BACKGROUND: After a spinal cord injury, patients have different perceptions of
sexuality, sexual function, and potential for fertility. These changes can
greatly impact quality of life over a lifetime. PURPOSE: The purpose of this
workgroup was to identify common evidence based or expert opinion themes and
recommendations regarding treatment of sexuality, sexual function and fertility
in the spinal cord injury population. METHODS: As part of the SIU-ICUD joint
consultation of Urologic Management of the Spinal Cord Injury (SCI), a workgroup
and comprehensive literature search of English language manuscripts regarding
fertility and sexuality in the spinal cord injury patient were formed. Articles
were compiled, and recommendations in the chapter are based on group discussion
and follow the Oxford Centre for Evidence-based Medicine system for levels of
evidence (LOEs) and grades of recommendation (GORs). RESULTS: Genital arousal,
ejaculation, and orgasm are significantly impacted after spinal cord injury in
both male and female SCI patients. This may have a more significant impact on
potential for fertility in male spinal cord injury patients, particularly
regarding ability of generate erection, semen quantity and quality. Female
patients should be consulted that pregnancy is still possible after injury and a
woman should expect resumption of normal reproductive function. As a result,
sexual health teaching should be continued in women despite injury. Pregnancy in
a SCI may cause complications such as autonomic dysreflexia, so this group should
be carefully followed during pregnancy. CONCLUSIONS: By understanding physiologic
changes after injury, patients and care teams can work together to achieve goals
and maximize sexual quality of life after the injury.
PMID- 29948053
TI - Synchronous colorectal cancer using CT colonography vs. other means: a systematic
review and meta-analysis.
AB - OBJECTIVES: The objective of our study was to systematically review the evidence
about synchronous colorectal cancer diagnosed with or without computed tomography
colonography (CTC). MATERIALS AND METHODS: Two systematic searches were performed
(PubMed and EMBASE) for studies reporting the prevalence of synchronous
colorectal cancer (CRC): one considering patients who underwent CTC and the
another one considering patients who did not undergo CTC. A three-level analysis
was performed to determine the prevalence of patients with synchronous CRC in
both groups of studies. Heterogeneity was explored for multiple variables. Pooled
prevalence and 95% confidence interval (CI) were calculated. A quality assessment
(STROBE) was done for the studies. RESULTS: For CTC studies, among 2645 articles
initially found, 21 including 1673 patients, published from 1997 to 2018, met the
inclusion criteria. For non-CTC studies, among 6192 articles initially found, 27
including 111,873 patients published from 1974 to 2015 met the inclusion
criteria. The pooled synchronous CRC prevalence was 5.7% (95% CI 4.7%-7.1%) for
CTC studies, and 3.9% (95% CI 3.3%-4.4%) for non-CTC studies, with a significant
difference (p = 0.004). A low heterogeneity was found for the CTC group (I2 =
10.3%), whereas a high heterogeneity was found in the non-CTC group of studies
(I2 = 93.5%), and no significant explanatory variables were found. Of the 22
STROBE items, a mean of 18 (82%) was fulfilled by CTC studies, and a mean of 16
(73%) by non-CTC studies. CONCLUSIONS: The prevalence of synchronous CRC was
about 4-6%. The introduction of CTC is associated with a significant increase of
the prevalence of synchronous CRCs.
PMID- 29948054
TI - The collar button ulcer sign.
PMID- 29948055
TI - Cobblestone sign.
PMID- 29948056
TI - Society of Abdominal Radiology disease-focused panel on renal cell carcinoma:
update on past, current, and future goals.
AB - The disease-focused panel (DFP) program was created by the Society of Abdominal
Radiology (SAR) as a mechanism to "improve patient care, education, and research"
in a "particular disease or a particular aspect of a disease". The DFP on renal
cell carcinoma (RCC) was proposed in 2014 and has been functional for 4 years.
Although nominally focused on RCC, the scope of the DFP has included
indeterminate renal masses because many cannot be assigned a specific diagnosis
when detected. Since its founding, the DFP has been active in a variety of
clinical, research, and educational projects to optimize the care of patients
with known or suspected RCC. The DFP is utilizing multi-institutional and cross
disciplinary collaboration to differentiate benign from malignant disease,
optimize the management of early stage RCC, and ultimately to differentiate
indolent from aggressive cancers. Several additional projects have worked to
develop a quantitative biomarker that predicts metastatic RCC response to anti
angiogenic therapy. While disease focus is the premise by which all DFPs are
created, it is likely that in the future the RCC DFP will need to expand or
create new panels that will focus on other specific aspects of RCC-a result that
the program's founders envisioned. New knowledge creates a need for more focus.
PMID- 29948057
TI - Feasibility and diagnostic performance of hybrid PET/MRI compared with PET/CT for
gynecological malignancies: a prospective pilot study.
AB - PURPOSE: The purpose of the study was to assess the feasibility and diagnostic
performance of FDG-PET/MR imaging compared to PET/CT for staging of patients with
a gynecological malignancy. METHODS: 25 patients with a gynecological malignancy
were prospectively enrolled into this pilot study. Patients underwent sequential
full-body PET/CT and PET/MR of the abdomen and pelvis after administration of a
single dose of F-18 FDG. PET/MRI and PET/CT images were independently reviewed by
two expert radiologists. Readers were blinded to the results of the other imaging
procedures. Clinical and pathologic information was abstracted from medical
charts. RESULTS: 18 patients were included in the final analysis with a median
age of 62 years (range 31-88). 61% of patients (11/18) had cervical cancer, while
the remaining patients had endometrial cancer. PET/MRI as compared to PET/CT
detected all primary tumors, 7/7 patients with regional lymph nodes, and 1/1
patient with an abdominal metastasis. Two patients had additional lymph nodes
outside of the abdominopelvic cavity detected on PET/CT that were not seen on
PET/MRI, whereas 6 patients had parametrial invasion and one patient had invasion
of the bladder seen on PET/MRI not detected on PET/CT. Five cervical cancer
patients had discordant clinical vs. radiographic staging based on PET/MRI
detection of soft tissue involvement. Management changed for two patients who had
clinical stage IB1 and radiographic stage IIB cervical cancer. CONCLUSIONS:
PET/MRI is feasible and has at least comparable diagnostic ability to PET/CT for
identification of primary cervical and endometrial tumors and regional
metastases. PET/MRI may be superior to PET/CT for initial radiographic assessment
of cervical cancers.
PMID- 29948058
TI - Vascular liver disorders: radiology at the center of patient management.
PMID- 29948059
TI - Qualitative and quantitative evaluation for morphological changes of the splenic
artery in autoimmune pancreatitis: novel imaging findings for differentiation
from pancreatic adenocarcinoma.
AB - PURPOSE: To determine whether morphological changes can occur in the splenic
artery (SPA) of autoimmune pancreatitis (AIP) cases, and if present, to compare
them with those in pancreatic adenocarcinoma (PAC) to clarify any arterial
morphological differences between AIP and PAC. METHODS: A total of 101 AIP cases
were included in this study. The presence or absence of morphological change in
the SPA was assessed, using arterial phase axial computed tomography images.
Subsequently, imaging parameters (imaging pattern, capsule-like rim, other organ
involvement, splenic vein [SPV] stenosis, and SPA calcification) were compared
between cases with and without morphological changes. Additionally, comparison
analyses (visual SPA assessment and % minimal lumen diameter [MLD] stenosis)
among normal pancreas, PAC, and AIP groups were performed using early arterial
phase (EAP) reconstructed images. RESULTS: In 25 (24.8%) AIP cases, marginal
irregularities of the SPA were present. The presence of the capsule-like rim and
SPV stenosis were significantly associated with the arterial morphological
changes. All cases with morphological changes had a capsule-like rim. Visual
assessment using EAP reconstructed images revealed irregularities of the SPA in 9
of 38 AIP cases (23.7%); however, arterial narrowing was not detected in any
cases. % MLD stenosis in AIP group was significantly lower than that in PAC group
(p < 0.0001). CONCLUSIONS: Although approximately one-quarter of AIP cases
potentially demonstrate marginal irregularity in the SPA when it is surrounded by
an apparent capsule-like rim, arterial luminal narrowing rarely occurs in
contrast to PAC. These arterial findings can help to distinguish AIP from PAC.
PMID- 29948060
TI - Local or extragastric recurrence after incomplete endoscopic submucosal
dissection of early gastric cancer: risk factors and the role of CT.
AB - PURPOSE: To investigate the risk factors of local and extragastric recurrence
after incomplete endoscopic submucosal dissection (ESD) of early gastric cancer
and the role of CT in the surveillance of extragastric recurrence. METHODS:
Institutional review board approval was obtained for this retrospective study
with waiver of informed consent. From January 2005 to April 2017, 2086 ESDs were
performed. Among them, 202 patients who received incomplete ESDs with positive
lateral or deep margins comprised our study population(M:F = 108:94, mean age =
63.3 years). Histopathology, size and depth of the tumor, margin status, and the
presence of lymphovascular invasion(LVI) were recorded. The patients were
followed-up for a mean period of 38.5 months (range 0.8-139 months). Univariate
and multivariate statistical analyses were performed to assess the risk factors
of local and extragastric recurrence. RESULTS: 96 patients had (+) lateral
margins, 90 had (+) deep margins and 16 had (+) lateral and deep margins. On
subsequent surgery and follow-up, local gastric recurrence was found in 54
patients and extragastric recurrence was present in 13 patients. On multivariate
analysis, (+) lateral margin [hazard radio (HR) 6.002; P < 0.0001] and tumor
size(HR 1.372; P = 0.009) were demonstrated to be significant risk factors for
local recurrence and (+) LVI was shown to be the only significant variable for
extragastric recurrence(HR 6.798, P = 0.002). CONCLUSION: A positive lateral
margin and tumor size were significant risk factors for local recurrence while
positive LVI was shown to be the only significant variable for extragastric
recurrence. Therefore, if LVI is positive in patients who received incomplete
ESD, subsequent surgery or follow-up with CT is recommended.
PMID- 29948061
TI - Fibrolamellar hepatocellular carcinoma: multiphasic CT features of the primary
tumor on pre-therapy CT and pattern of distant metastases.
AB - OBJECTIVE: The aim of our study is to describe the multiphasic CT features of
fibrolamellar hepatocellular carcinomas (FLHCCs) and pattern of distant
metastases. MATERIALS AND METHODS: 33 patients (mean age 28 years: 17M/16F) with
pathologically confirmed FLHCC and pre-treatment multiphasic CT were included in
the study. Two abdominal radiologists evaluated the multiphasic CT imaging
features of these 33 FLHCC patients in consensus. RESULTS: Solitary hepatic mass
was seen in 67% (22/33). Mean tumor size was 11.3 cm (range 4.6-22 cm). Tumor was
well-defined in 64% (21/33). In the pre-contrast CT, 91% (30/33) were
hypoattenuating. Central stellate scar was present in 73% (24/33). In FLHCC
having central stellate scar, calcification within the central scar was seen in
88% (21/24). In the hepatic arterial phase, 82% (27/33) were hyperattenuating
relative to liver. In the portal venous phase, 36% (12/33) were hyperattenuating,
46% (15/33) were isoattenuating, and 18% (6/33) were hypoattenuating. In the
delayed phase images, 24% (8/23) were hyperattenuating, 67% (22/33) were
isoattenuating, and 9% (3/33) were hypoattenuating. Delayed enhancement of the
central stellate scar was seen in 12% (4/33). Distant metastases were seen in 54%
(18/33). The most common site of metastases was lungs and was seen in 89% (16/18)
of the patients with metastatic disease. CONCLUSION: FLHCC typically manifests as
a large, solitary mass demonstrating heterogeneous hypervascular enhancement in
the arterial phase. Most tend to be isoattenuating in delayed phase. Central
stellate scar with internal calcification is a useful imaging feature that can
help in the diagnosis of FLHCC. Lungs are the most common site of distant
metastases in FLHCC.
PMID- 29948062
TI - Passive Coping Strategies Are Associated With More Impairment In Quality Of Life
In Patients With Fibrous Dysplasia.
AB - Impairments in quality of life (QoL) have been reported in patients with fibrous
dysplasia (FD). Here, we examine coping strategies in FD and assess whether these
coping strategies are associated with QoL and disease severity. Ninety-two
patients (66% females) filled out the Utrecht Coping List (UCL), Short Form-36,
and the Brief Pain Inventory (BPI). Coping strategies of patients with FD were
compared with reference data from a random sample of Dutch women and patients
with chronic pain. Compared to healthy adults, patients expressed more emotions
(p < 0.01). Compared to patients with chronic pain, patients with FD used more
active coping strategies (p < 0.001), and sought more distraction (p = 0.01) and
more social support (p < 0.001). Using more passive coping strategies was
associated with more impairment in social function, physical role, mental health,
vitality (all p < 0.001), and general health (p < 0.01). Using more avoidant
coping strategies was associated with worse mental health and less vitality (both
p < 0.01). More expression of emotions was associated with worse mental health (p
< 0.01). Type and clinical severity of FD were not associated with coping
behavior. Patients with FD have different coping strategies compared to random
Dutch reference populations with or without pain. In FD, using more passive
coping strategies was associated with more impairment in several aspects of QoL.
There was no relationship between coping behavior and clinical characteristics,
pointing to biomedical variables not determining the way patients cope with their
illness. Recognition of less effective coping strategies can be helpful in the
understanding and adaptation of these coping strategies, improving personalized
clinical care, with the ultimate goal to improve QoL in patients with FD.
PMID- 29948063
TI - Sub-millisievert CT colonography: effect of knowledge-based iterative
reconstruction on the detection of colonic polyps.
AB - OBJECTIVES: To assess the feasibility of ultra-low dose computed tomography
colonography (CTC) using knowledge-based iterative reconstruction (IR) and to
determine its effect on polyp detection. METHODS: Forty-nine prospectively
enrolled patients underwent ultra-low dose CTC in the supine (100 kVp/20 mAs) and
prone positions (80 kVp/20 mAs), followed by same-day colonoscopy. Thereafter,
images were reconstructed using filtered back projection (FBP) and knowledge
based IR (IMR; Philips Healthcare, Best, Netherlands) algorithms. Effective
radiation dose of CTC was recorded. Pooled per-polyp sensitivity and positive
predictive value of three radiologists was analysed and compared between FBP and
IMR. Image quality was assessed on a five-point scale and image noise was
recorded using standard deviations. RESULTS: Mean effective radiation dose of
ultra-low dose CTC was 0.90 +/- 0.06 mSv. Eighty-nine polyps were detected on
colonoscopy (mean, 8.5 +/- 4.7 mm). The pooled per-polyp sensitivity for polyps
6.0-9.9 mm (n = 22) on CTC reconstructed with IMR (36/66, 54.5%) was not
significantly different with that using FBP algorithm (34/66, 51.5%) (p = 0.414).
For polyps >=10 mm (n = 35), however, the pooled per-polyp sensitivity on CTC
with IMR (73/105, 69.5%) was significantly higher than that with FBP (55/105,
52.4%) (p < 0.001). In particular, the difference of per-polyp sensitivity was
statistically significant in intermediate (p = 0.014) and novice (p = 0.003)
reviewers. Furthermore, mean image noise of IMR (8.4 +/- 6.2 HU) was
significantly lower than that of FBP (37.5 +/- 13.9 HU) (p < 0.001) and image
quality with IMR was significantly better than with FBP in all evaluated segments
in all reviewers (all ps < 0.001). CONCLUSIONS: Sub-mSv CTC reconstructed with
IMR was feasible for the detection of clinically significant polyps,
demonstrating 70% per-polyp sensitivity of polyps >=10 mm, while allowing
significant noise reduction and improvement in image quality compared with FBP
reconstruction. KEY POINTS: * Sub-mSv CTC using IMR demonstrated 70% per-polyp
sensitivity for polyps >=10 mm. * CTC using IMR significantly outperformed CTC
reconstructed with FBP. * IMR allows significantly more noise reduction and
improvement in image quality than FBP.
PMID- 29948065
TI - Strain analysis is superior to wall thickening in discriminating between
infarcted myocardium with and without microvascular obstruction.
AB - OBJECTIVES: The aim of the present study was to evaluate the diagnostic
performances of strain and wall thickening analysis in discriminating among three
types of myocardium after acute myocardial infarction: non-infarcted myocardium,
infarcted myocardium without microvascular obstruction (MVO) and infarcted
myocardium with MVO. METHODS: Seventy-one patients with a successfully treated ST
segment elevation myocardial infarction underwent cardiovascular magnetic
resonance imaging at 2-6 days after reperfusion. The imaging protocol included
conventional cine imaging, myocardial tissue tagging and late gadolinium
enhancement. Regional circumferential and radial strain and associated strain
rates were analyzed in a 16-segment model as were the absolute and relative wall
thickening. RESULTS: Hyperenhancement was detected in 418 (38%) of 1096 segments
and was accompanied by MVO in 145 (35%) of hyperenhanced segments. Wall
thickening, circumferential and radial strain were all significantly diminished
in segments with hyperenhancement and decreased even further if MVO was also
present (all p < 0.001). Peak circumferential strain (CS) surpassed all other
strain and wall thickening parameters in its ability to discriminate between
hyperenhanced and non-enhanced myocardium (all p < 0.05). Furthermore, CS was
superior to both absolute and relative wall thickening in differentiating
infarcted segments with MVO from infarcted segments without MVO (p = 0.02 and p =
0.001, respectively). CONCLUSIONS: Strain analysis is superior to wall thickening
in differentiating between non-infarcted myocardium, infarcted myocardium without
MVO and infarcted myocardium with MVO. Peak circumferential strain is the most
accurate marker of regional function. KEY POINTS: * CMR can quantify regional
myocardial function by analysis of wall thickening on cine images and strain
analysis of tissue tagged images. * Strain analysis is superior to wall
thickening in differentiating between different degrees of myocardial injury
after acute myocardial infarction. * Peak circumferential strain is the most
accurate marker of regional function.
PMID- 29948064
TI - Radial diffusivity as an imaging biomarker for early diagnosis of non-demented
amyotrophic lateral sclerosis.
AB - OBJECTIVES: To explore the sensitivity of potential DTI-based biomarkers in
detecting microstructural changes for whole-brain white matter in early stage
amyotrophic lateral sclerosis (ALS), analyze the relationship between the DTI
indices and disease status, and further clarify potential brain regions for
disease monitoring and clinical assessment. METHODS: Thirty-three non-demented
ALS patients and 32 age- and gender-matched subjects participated in this study.
DTI data were acquired via 3.0T MRI scanner. Maps of diffusion-related indices
including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity
(AD), and radial diffusivity (RD) were obtained. Tract-based spatial statistics
(TBSS) were used to investigate whole-brain white matter changes of each index.
Correlation analyses between both brain-wide and volume-of-interest (VOI)-wide
white matter alterations and clinical factors including ALSFRS-R scores, disease
duration, and progression rate were performed. RESULTS: Compared to healthy
subjects, ALS patients showed significantly increased RD, MD and reduced FA,
mainly along the corticospinal tract (CST) and the body of corpus callosum (CC).
Increases in RD were broader than decreases in FA, in CST of both hemispheres.
Meanwhile, involvement of several extra-motor regions was also revealed by RD.
Significant positive correlation between ALSFRS-R scores and FA, negative
correlation between ALSFRS-R and RD were found in left CST. CONCLUSIONS: RD may
be the most sensitive biomarker for the detection of early demyelination of white
matter. Both RD and FA may serve as objective biomarkers for disease severity
assessment. CST may be the most affected brain region in non-demented ALS. KEY
POINTS: * Changes in RD were broader than those in FA in bilateral CST. *
Involvement of extra-motor regions was uncovered by RD. * FA and RD in CST were
related to ALSFRS-R scores.
PMID- 29948066
TI - Correction to: Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with
CT Brody score and lung function in cystic fibrosis patients.
AB - The original version of this article, published on 13 April 2018, unfortunately
contained a mistake.
PMID- 29948067
TI - Vertebral augmentation with the SpineJack(r) in chronic vertebral compression
fractures with major kyphosis.
AB - OBJECTIVES: Osteoporotic vertebral compression fractures (OVCFs) are an important
health issue for which minimally invasive techniques are a feasible treatment.
The SpineJack(r) (Vexim) is an intravertebral expandable system designed to
improve the correction of the structural modifications caused by OVCFs. Its
ability to stabilise and reduce OVCFs at the acute phase being already well
established, we sought to evaluate the feasibility of vertebral augmentation with
the SpineJack(r) in chronic kyphotic OVCFs. METHODS: All consecutive patients
treated with the SpineJack(r) were prospectively included if they met the
following criteria: (1) OVCF considered unstable (grade A3 according to Magerl's
classification). (2) Local kyphotic angle >= 20 degrees . (3) OVCF older than 6
weeks. (4) Back pain with visual analogue scale (VAS) >= 4. RESULTS: Nineteen
consecutive patients (16 women [84.2%] and 3 men [15.8%]; mean age 73.2 +/- 8.2
years) were included. Treatment was performed after a mean delay of 5.8 months +/
2.9 (range 1.5-12). Median visual analogue scale significantly improved from 7
preoperatively (IQR 6-9) to 2 (IQR 1-5) at 6 months (p < 0.01). Significant
kyphosis reduction (i.e. >= 30%) was obtained in 94.7% of cases. Secondary
adjacent level fractures (SALFs) were noted in 21.1% of cases and were correlated
with the importance of the kyphosis reduction. CONCLUSIONS: Vertebral
augmentation with the SpineJack(r) is feasible and seems able to correct major
structural deformities in chronic OVCFs. SALFs were noted in a substantial amount
of cases. Preventive adjacent vertebroplasty might be useful in patients with
several risk factors for SALFs. KEY POINTS: * Vertebral augmentation with
SpineJack(r) is effective to correct major structural deformities e.g. height
loss and kyphosis. * Successful reduction is reachable with SpineJack(r) in
chronic (older than 6 weeks) OVCFs. * Aggressive reduction of major kyphosis
might promote SALFs and complementary adjacent vertebroplasties prevent their
occurrence.
PMID- 29948068
TI - Gliosarcoma: a clinical and radiological analysis of 48 cases.
AB - OBJECTIVES: To retrospectively review the radiological and clinicopathological
features of gliosarcoma (GSM) and differentiate it from glioblastoma multiforme
(GBM). METHODS: The clinicopathological data and imaging findings (including
VASARI analysis) of 48 surgically and pathologically confirmed GSM patients
(group 1) were reviewed in detail, and were compared with that of other
glioblastoma (GBM) cases in our hospital (group 2). RESULTS: There were 28 men
and 20 women GSM patients with a median age of 52.5 years (range, 24-80 years) in
this study. Haemorrhage (n = 21), a salt-and-pepper sign on T2-weighted images (n
= 36), unevenly thickened wall (n = 36) even appearing as a paliform pattern (n =
32), an intra-tumoural large feeding artery (n = 32) and an eccentric cystic
portion (ECP) (n = 19) were more commonly observed in the GSM group than in GBM
patients. Based on our experience, GSM can be divided into four subtypes
according to magnetic resonance imaging (MRI) features. When compared to GBM
(group 2), there were more patients designated with type III lesions (having very
unevenly thickened walls) and IV (solid) lesions among the GSM cases (group 1).
On univariate prognostic analysis, adjuvant therapy (radiotherapy, chemotherapy,
and radiochemotherapy) and existence of an eccentric cyst region were prognostic
factors. However, Cox's regression model showed only adjuvant therapy as a
prognostic factor for GSM. CONCLUSIONS: When compared to GBM, certain imaging
features are more likely to occur in GSM, which may help raise the possibility of
this disease. All GSM patients are recommended to receive adjuvant therapy to
achieve a better prognosis with radiotherapy, chemotherapy or radiochemotherapy
all as options. KEY POINTS: * Diagnosis of gliosarcoma can be suggested
preoperatively by imaging. * Gliosarcoma can be divided into four subtypes based
on MRI. * Paliform pattern and ECP tend to present in gliosarcoma more than GBM.
* The cystic subtype of gliosarcoma may predict a more dismal prognosis. * All
gliosarcoma patients should receive adjuvant therapy to achieve better prognosis.
PMID- 29948069
TI - Evaluation of MR-derived CT-like images and simulated radiographs compared to
conventional radiography in patients with benign and malignant bone tumors.
AB - OBJECTIVES: To evaluate the diagnostic value of MR-derived CT-like images and
simulated radiographs compared with conventional radiographs in patients with
benign and malignant bone tumors. METHODS: In 32 patients with a benign or
malignant bone lesion (mean age 33.9 +/- 18.5 years, 17 females), 3-T MR imaging
was performed including a 3D T1-weighted gradient echo sequence as the basis for
the CT-like images. From these, intensity-inverted MR image volumes were
converted into 2D images via a forward projection to obtain simulated
radiographs. Two radiologists assessed these images as well as conventional
radiographs for the type of periosteal reaction, matrix mineralization and
destruction pattern. Agreement between the modalities was calculated using
Cohen's kappa. RESULTS: The agreement between conventional radiographs and MR
derived CT-like images in combination with simulated radiographs was substantial
(periosteal reaction, kappa = 0.67; destruction pattern, kappa = 0.75), and the
sensitivity of both modalities for the final diagnosis of the lesion (aggressive
vs. nonaggressive) was high (MR-derived CT-like images, 86.2% vs. conventional
radiographs, 90.0%). Additional information on soft tissue extension (MR-derived
CT-like images, 21.9% vs. conventional radiographs, 12.5%; p = 0.009) and
lobulation (9.4% vs. 0%; p < 0.001) was significantly more often found on MR
derived CT-like images compared with conventional radiographs. CONCLUSIONS: The
assessment of the destruction patterns, periosteal reaction and distinction
between aggressive and nonaggressive tumors was feasible using MR-derived CT-like
images and simulated radiographs and is comparable to that of conventional
radiographs. Moreover, MR-derived CT-like images provided additional information
on soft tissue extension and tumor architecture. KEY POINTS: * CT-like images and
simulated radiographs can be generated from 3D MRI. * Evaluation of bone tumors
is feasible with MR-derived images. * CT-like images and simulated radiographs
provide additional information on bone tumors.
PMID- 29948070
TI - Efficacy of contrast-enhanced FDG PET/CT in patients awaiting liver
transplantation with rising alpha-fetoprotein after bridge therapy of
hepatocellular carcinoma.
AB - OBJECTIVE: To assess the diagnostic accuracy and illustrate positive findings of
contrast-enhanced fluorine-18 fluoro-D-glucose positron emission
tomography/computed tomography (18F-FDG PET/CT) image in patients awaiting liver
transplantation (LT) with rising alpha-fetoprotein (AFP) after bridge therapy of
hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective study
included 100 patients who were waiting for LT and who previously underwent
locoregional therapy (LRT) of HCC. These patients had rising AFP levels on a
routine follow-up examination awaiting LT. All patients underwent a contrast
enhanced 18F-FDG PET/CT examination. We calculated for each patient the maximum
standardised uptake value (SUVmax) of the tumour and the ratio of the tumoral
SUVmax to the normal-liver SUVmax. The diagnostic accuracy and positive contrast
enhanced findings of 18F-FDG PET/CT were established by histopathology and
clinical and imaging follow-up as the reference standards. RESULTS: Contrast
enhanced 18F-FDG PET/CT detected tumour relapse in 78 patients (13 patients had
intrahepatic lesions, 10 patients had extrahepatic metastases and 55 patients
with combined lesions). The sensitivity, specificity and accuracy values of
contrast-enhanced 18F-FDG PET/CT examination in the detection of HCC recurrence
were 92.8%, 94.1% and 93%, respectively. A significant correlation was found
between the AFP level and SUVmax ratio (r = 0.2283; p = 0.0224). The best
threshold for 18F-FDG PET positivity was >1.21. CONCLUSION: Contrast-enhanced 18F
FDG PET/CT is a valuable tool for the detection of intrahepatic HCC recurrence or
extrahepatic metastasis following rising AFP levels after LRT of HCC, and should
be incorporated during routine workup awaiting LT. KEY POINTS: * 18F-FDG PET/CT
is a valuable tool for the detection of HCC recurrence * 18 F-FDG PET/CT should
be incorporated during routine workup awaiting liver transplantation *
Significant correlation was found between AFP level and SUVmax ratio * The best
threshold for 18 F-FDG PET positivity was >1.21 * The ideal cut-off value for AFP
was >202.
PMID- 29948071
TI - Large-volume iodinated contrast medium extravasation: low frequency and good
outcome after conservative management in a single-centre cohort of more than
67,000 patients.
AB - OBJECTIVES: Our aim was to retrospectively investigate the frequency and outcome
of large-volume iodinated contrast medium (CM) extravasation in our institution
and to compare our management protocol to current practice. METHODS:
Institutional review board approval was obtained, and informed consent was waived
because the study was retrospective. From January 2008 to September 2016,
radiological examinations with intravenous non-ionic iodinated CM administration
were performed in 67,129 patients. Contrast medium extravasation events on CT
scans and intravenous pyelograms but not on angiograms were included. All data
were collected prospectively and stratified according to age, injection method
(manual vs auto-injection), prevention of extravasation by various means
(including intercom alarm), management of extravasation (routine application of
silver sulfadiazine ointment, clobetasol propionate cream, and damp gauze at room
temperature), etc. RESULTS: The incidence of large-volume CM extravasation was
very low (0.04% [27/67,129] overall; 0.03% related to manual injection [age
range, 59-92 years; mean, 75.4 years], and 0.045% related to auto-injection [age
range, 36-86 years; mean, 65.8 years]). The CM extravasation volume in majority
of patients was 20-40 ml in 5 of 9 patients (55.6%) in the manual injection group
and 14 of 18 (77.8%) in the auto-injection group. Swelling and pain were the most
common symptoms. No patient developed severe signs or needed surgical
intervention. CONCLUSIONS: Results show a very low incidence of large-volume CM
extravasation without severe complications or sequelae. The casual effect between
our protocols and good outcome cannot be scrutinised thoroughly because the study
lacks a control group and is retrospective. KEY POINTS: * The incidence of large
volume contrast medium extravasation (>=20 ml) was 0.04%. * No patient needed
surgical intervention, and most recovered within 7 days. * Each element of our
management protocol contributed to good outcome.
PMID- 29948072
TI - Prediction of outcome after aneurysmal subarachnoid haemorrhage using data from
patient admission.
AB - OBJECTIVES: The pathogenesis leading to poor functional outcome after aneurysmal
subarachnoid haemorrhage (aSAH) is multifactorial and not fully understood. We
evaluated a machine learning approach based on easily determinable clinical and
CT perfusion (CTP) features in the course of patient admission to predict the
functional outcome 6 months after ictus. METHODS: Out of 630 consecutive
subarachnoid haemorrhage patients (2008-2015), 147 (mean age 54.3, 66.7% women)
were retrospectively included (Inclusion: aSAH, admission within 24 h of ictus,
CTP within 24 h of admission, documented modified Rankin scale (mRS) grades after
6 months. Exclusion: occlusive therapy before first CTP, previous aSAH, CTP not
evaluable). A random forests model with conditional inference trees was optimised
and trained on sex, age, World Federation of Neurosurgical Societies (WFNS) and
modified Fisher grades, aneurysm in anterior vs. posterior circulation, early
external ventricular drainage (EVD), as well as MTT and Tmax maximum, mean,
standard deviation (SD), range, 75th quartile and interquartile range to predict
dichotomised mRS (<= 2; > 2). Performance was assessed using the balanced
accuracy over the training and validation folds using 20 repeats of 10-fold cross
validation. RESULTS: In the final model, using 200 trees and the synthetic
minority oversampling technique, median balanced accuracy was 84.4% (SD 0.7) over
the training folds and 70.9% (SD 1.2) over the validation folds. The five most
important features were the modified Fisher grade, age, MTT range, WFNS and early
EVD. CONCLUSIONS: A random forests model trained on easily determinable features
in the course of patient admission can predict the functional outcome 6 months
after aSAH with considerable accuracy. KEY POINTS: * Features determinable in the
course of admission of a patient with aneurysmal subarachnoid haemorrhage (aSAH)
can predict the functional outcome 6 months after the occurrence of aSAH. * The
top five predictive features were the modified Fisher grade, age, the mean
transit time (MTT) range from computed tomography perfusion (CTP), the WFNS grade
and the early necessity for an external ventricular drainage (EVD). * The range
between the minimum and the maximum MTT may prove to be a valuable biomarker for
detrimental functional outcome.
PMID- 29948073
TI - Real-time MR-guided brain biopsy using 1.0-T open MRI scanner.
AB - OBJECTIVES: To evaluate the safety, feasibility and diagnostic performance of
real-time MR-guided brain biopsy using a 1.0-T open MRI scanner. METHODS: Medical
records of 86 consecutive participants who underwent brain biopsy under the
guidance of a 1.0-T open MRI scanner with real-time and MR fluoroscopy techniques
were evaluated retrospectively. All procedures were performed under local
anaesthesia and intravenous conscious sedation. Diagnostic yield, diagnostic
accuracy, complication rate and procedure duration were assessed. The lesions
were divided into two groups according to maximum diameters: <= 1.5 cm (n = 16)
and > 1.5 cm (n = 70). The two groups were compared using Fisher's exact test.
RESULTS: Diagnostic yield and diagnostic accuracy were 95.3% and 94.2%,
respectively. The diagnostic yield of lesions <= 1.5 cm and > 1.5 cm were 93.8%
and 95.7%, respectively. There was no significant difference in diagnostic yield
between the two groups (p > 0.05). Mean procedure duration was 41 +/- 5 min
(range 33-49 min). All biopsy needles were placed with one pass. Complication
rate was 3.5% (3/86). Minor complications included three cases of a small amount
of haemorrhage. No serious complications were observed. CONCLUSIONS: Real-time MR
guided brain biopsy using a 1.0-T open MRI scanner is a safe, feasible and
accurate diagnostic technique for pathological diagnosis of brain lesions. The
procedure duration is shortened and biopsy work flow is simplified. It could be
considered as an alternative for brain biopsy. KEY POINTS: * Real-time MRI-guided
brain biopsy using a 1.0-T open MRI scanner is safe, feasible and accurate. * No
serious complications occurred in real-time MRI-guided brain biopsy. * Procedure
duration is shortened and biopsy work flow is simplified.
PMID- 29948074
TI - A clinical-radiomics nomogram for the preoperative prediction of lung metastasis
in colorectal cancer patients with indeterminate pulmonary nodules.
AB - OBJECTIVES: To develop and validate a clinical-radiomics nomogram for
preoperative prediction of lung metastasis for colorectal cancer (CRC) patients
with indeterminate pulmonary nodules (IPN). METHODS: 194 CRC patients with lung
nodules were enrolled in this study (136 in the training cohort and 58 in the
validation cohort). To evaluate the probability of lung metastasis, we developed
three models, the clinical model with significant clinical risk factors, the
radiomics model with radiomics features constructed by the least absolute
shrinkage and selection operator algorithm, and the clinical-radiomics model with
significant variables selected by the stepwise logistic regression. The Akaike
information criterion (AIC) was used to compare the relative strength of
different models, and the area under the curve (AUC) was used to quantify the
predictive accuracy. The nomogram was developed based on the most appropriate
model. Decision-curve analysis was applied to assess the clinical usefulness.
RESULTS: The clinical-radiomics model (AIC = 98.893) with the lowest AIC value
compared with that of the clinical-only model (AIC = 138.502) or the radiomics
only model (AIC = 116.146) was identified as the best model. The clinical
radiomics nomogram was also successfully developed with favourable discrimination
in both training cohort (AUC = 0.929, 95% CI: 0.885-0.974) and validation cohort
(AUC = 0.922, 95% CI: 0.857-0.986), and good calibration. Decision-curve analysis
confirmed the clinical utility of the clinical-radiomics nomogram. CONCLUSIONS:
In CRC patients with IPNs, the clinical-radiomics nomogram created by the
radiomics signature and clinical risk factors exhibited favourable discriminatory
ability and accuracy for a metastasis prediction. KEY POINTS: * Clinical features
can predict lung metastasis of colorectal cancer patients. * Radiomics analysis
outperformed clinical features in assessing the risk of pulmonary metastasis. * A
clinical-radiomics nomogram can help clinicians predict lung metastasis in
colorectal cancer patients.
PMID- 29948075
TI - Comparison of diagnostic performance between CT and MRI in differentiating non
diffuse-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma.
AB - OBJECTIVES: To intraindividually compare the diagnostic performance of CT and MRI
in differentiating non-diffuse-type autoimmune pancreatitis (AIP) from pancreatic
ductal adenocarcinoma (PDA). METHODS: Sixty-one patients with non-diffuse-type
AIP and 122 patients with PDA, who underwent dynamic contrast-enhanced CT and MRI
with MR pancreatography, were included. Two blinded radiologists independently
rated their confidence in differentiating the two diseases on a 5-point scale,
and the diagnostic performances of CT and MRI were compared. The presence of key
imaging features to differentiate AIP and PDA were compared between CT and MRI.
RESULTS: The area under the receiver operating characteristic curve was
significantly greater on MRI (0.993-0.995) than on CT (0.953-0.976) for both
raters (p<=0.035). The sensitivities of MRI were higher than those of CT for the
diagnosis of AIP (88.5-90.2% vs. 77-80.3%, p<=0.07) and PDA (97.5-99.2% vs. 91.8
94.3%, p<=0.031) for both raters, although the difference for AIP was
statistically marginal (p=0.07) for rater 1. In AIP, multiple pancreatic masses,
delayed homogeneous enhancement of the pancreatic mass, and multiple main
pancreatic duct (MPD) strictures were observed significantly more frequently
using MRI than CT (p<=0.008). In PDA, discrete pancreatic mass and MPD stricture
were observed significantly more frequently using MRI than CT (p<=0.012).
CONCLUSIONS: The diagnostic performance of MRI is better for differentiating non
diffuse-type AIP from PDA, which is due to the superiority of MRI over CT in
demonstrating the key distinguishing features of both diseases. KEY POINTS: *
Imaging differential diagnosis of non-diffuse-type AIP and PDA is challenging. *
MRI has better diagnostic performance than CT in differentiating non-diffuse-type
AIP from PDA. * MRI is superior to CT in demonstrating key distinguishing
features of non-diffuse-type AIP and PDA.
PMID- 29948076
TI - Usefulness of feature analysis of breast-specific gamma imaging for predicting
malignancy.
AB - OBJECTIVES: The purpose of this study was to investigate which feature of the
breast-specific gamma imaging (BSGI) uptake in women who were recently diagnosed
with breast cancer was associated with malignancy. METHODS: Data on 231 newly
diagnosed breast cancer patients who underwent preoperative BSGI were
retrospectively reviewed. Feature analysis was done by classifying BSGI uptake
into mass, non-mass, or focus/foci. Descriptors for mass, non-mass, or focus/foci
were shape, distribution, number, and intensity. BSGI features of known
malignancies and lesions that were additionally found by BSGI were correlated
with mammographic breast density, histology, hormonal status, and clinical follow
up data obtained over at least 2 years. RESULTS: Among 372 breast lesions from
231 patients, 241 malignancies had been pathologically confirmed prior to BSGI
and 131 additional lesions were found on BSGI. Irregular shape was more
predictive of malignancy than oval shape (p=0.004) in mass uptake. Linear/ductal
distribution was more predictive of malignancy than focal, regional, and
segmental distribution (p<0.05) in non-mass uptake. Mammographic breast density
was not associated with BSGI features. The lesion to normal ratio (LNR) was
higher in the postmenopausal patients than that in the premenopausal patients
(p=0.003). CONCLUSIONS: The feature analysis of radiotracer uptake in BSGI is
useful in predicting whether breast lesions are malignant or benign. KEY POINTS:
* The feature analysis of BSGI uptake is useful in predicting malignancy. *
Irregular shape was predictive of malignancy in mass uptake. * Linear/ductal
distribution was predictive of malignancy in non-mass uptake.
PMID- 29948077
TI - The value of blood oxygen level dependent (BOLD) imaging in evaluating post
operative renal function outcomes after laparoscopic partial nephrectomy.
AB - OBJECTIVES: To assess the ability of renal blood oxygen level dependent (BOLD)
MRI metrics to predict post-operative renal function. METHODS: We studied 152
patients who underwent laparoscopic partial nephrectomy (LPN) and renal MRI
examination including BOLD. Short-term and long-term renal function was evaluated
using the glomerular filtration rate (GFR) derived from renal scintigraphy. Renal
function decline was assessed as the absolute decline (AD), percentage decline
(PD) and optimal renal function preservation (OP). T2* values were analysed in
the renal cortex and medulla ipsilateral and contralateral to the tumour.
Clinical characteristics and imaging metrics were evaluated using univariate and
multivariate linear regression analyses. Risk factors obtained using BOLD metrics
(determined by multivariate regression) were then combined and compared with
RENAL scores to predict OP. RESULTS: Increasing warm ischaemia time (WIT),
resected and ischaemic volume (RAIV), larger tumour size, higher RENAL score and
lower preoperative GFR were short-term risk factors for AD, while increasing WIT
and lower preoperative GFR were significant for long-term outcomes. Increasing
WIT, RAIV, lower T2* value in the cortex and higher T2* value in the medulla on
the ipsilateral side were short-term risk factors for PD, while all of the above
factors (except WIT and RAIV) were significant for long-term outcomes. The
performance of the combination of T2* values in the cortex and medulla on the
ipsilateral side to tumour in predicting OP was better than RENAL score (AUC
0.762 vs 0.634, p = 0.013). CONCLUSIONS: Renal BOLD-MRI metrics could provide
useful information to the clinician in predicting post-operative renal function
outcomes. KEY POINTS: * Renal fMRI metrics may be useful for prediction of renal
functional outcomes and merit further study. * Renal fMRI metrics may reflect
degree of baseline disease and ability to tolerate warm ischaemia. * Combination
of T2* values was better than RENAL score for predicting OP.
PMID- 29948078
TI - Bone susceptibility mapping with MRI is an alternative and reliable biomarker of
osteoporosis in postmenopausal women.
AB - OBJECTIVES: To investigate the efficacy of quantitative susceptibility mapping
(QSM) in the assessment of osteoporosis for postmenopausal women. METHODS:
Between May and September 2017, a total of 70 postmenopausal women who underwent
MRI-based QSM and quantitative computed tomography (QCT) were consecutively
enrolled in this prospective study. The measurement of QSM and QCT values was
performed on the L3 vertebrae body. On the basis of QCT value, all individuals
were divided into three groups (normal, osteopenia and osteoporosis). RESULTS: On
the basis of QCT, 18 individuals were normal (25.7%), 26 osteopenic (37.1%) and
26 osteoporotic (37.1%). The QSM value was age-related (p = 0.04) and
significantly higher in the osteoporosis group than in either the normal or
osteopenia group (for all, p < 0.001). In addition, the QSM value was highly
correlated with QCT value (r = - 0.720, p < 0.001). For QSM, the area under the
curve (AUC), sensitivity and specificity for differentiating osteopenia from non
osteopenia were 0.88, 86.5% and 77.8%, respectively, and for differentiating
osteoporosis from non-osteoporosis they were 0.86, 80.8% and 77.3%, respectively.
CONCLUSIONS: MRI-based QSM could be used for quantifying susceptibility in
vertebrae and has the potential to be a new biomarker in the assessment of
osteoporosis for postmenopausal women. KEY POINTS: * Osteoporosis significantly
increases risk of fracture for postmenopausal women. * QSM value was correlated
with QCT value (r = - 0.72, p < 0.001). * QSM is feasible in the assessment of
osteoporosis for postmenopausal women. * QSM offers the quantification of
susceptibility within bone.
PMID- 29948079
TI - Prostate artery embolisation for benign prostatic hyperplasia: a systematic
review and meta-analysis.
AB - OBJECTIVES: Prostate artery embolisation (PAE) is a new minimally invasive
treatment for lower urinary tract symptoms (LUTS) in men with benign prostatic
hyperplasia (BPH). The purpose of this study was to review the efficacy and
safety of PAE in the treatment of BPH with LUTS. METHODS: A systematic review
performed according to the PRISMA guidelines with a pre-specified search strategy
for PubMed, Web of Science, Cochrane Library and Embase databases protocol
(PROSPERO ID: CRD42017059196). Trials studying the efficacy of prostate artery
embolisation to treat LUTS with more than ten participants and follow-up longer
than 6 months were included by two independent authors. Outcomes investigated
were International Prostate Symptom Score (IPSS), quality of life (QoL),
International Index of Erectile Function (IIEF-5), prostate volume (PV), prostate
specific antigen (PSA), peak void flow (Qmax), post-void residual (PVR) and
complications. To summarise mean change from baseline, a meta-analysis was done
using the random-effects model. RESULTS: The search returned 210 references, of
which 13 studies met the inclusion criteria, representing 1,254 patients.
Patients in the included studies with data available for meta-analysis had
moderate to severe LUTS and a mean IPSS of 23.5. Statistically significant (p
value < 0.05) improvements of all investigated outcomes were seen at 12-month
follow-up. Major complications were reported in 0.3% of the cases. CONCLUSIONS:
Our findings suggest that PAE can reduce moderate to severe LUTS in men with BPH
with a low risk of complications. KEY POINTS: * Prostate artery embolisation
(PAE) improved International Prostate Symptom Score (IPSS) by 67%. * Major
complications after PAE are very rare. * Use of cone-beam CT may reduce risk of
non-target embolisation.
PMID- 29948080
TI - Correlation of texture analysis of paraspinal musculature on MRI with different
clinical endpoints: Lumbar Stenosis Outcome Study (LSOS).
AB - OBJECTIVES: The aim of this study was to apply texture analysis (TA) on
paraspinal musculature in T2-weighted (T2w) magnetic resonance images (MRI) of
symptomatic lumbar spinal stenosis (LSS) patients and correlate the findings with
clinical outcome measures. METHODS: Ninety patients were prospectively enrolled
in the multi-centric Lumbar Stenosis Outcome Study (LSOS). All patients received
a T2w MRI, from which we selected axial images perpendicular to the
intervertebral disc at level L3/4 for TA. Regions-of-interest (ROI) were drawn of
the paraspinal musculature and 304 TA features/ ROI were calculated. As clinical
outcome measurements, we analysed three commonly applied measures: Spinal
Stenosis Measure (SSM), Roland-Morris Disability Questionnaire (RMDQ), as well as
the Numeric Rating Scale (NRS). We used two machine learning-based classifiers:
Decision table, and k-nearest neighbours (k-NN). RESULTS: We observed no
meaningful correlation between TA in paraspinal musculature and the two clinical
outcome measures SSM symptoms and SSM function, while a moderate correlation was
observed regarding the outcome measures RMDQ (k-NN: r = 0.56) and NRS (Decision
Table: r = 0.72). CONCLUSIONS: In conclusion, MR TA is a viable tool to quantify
medical images and illustrate correlations of microarchitectural changes
invisible to a human reader with potential clinical impact. KEY POINTS: * TA is
feasible on paraspinal musculature using MRI. * TA on paraspinal musculature
correlates with SSM and RMDQ. * TA may enable a statement regarding clinical
impact of imaging findings.
PMID- 29948081
TI - Ventricular Myocardial Fat: An Unexpected Biomarker for Long-term Survival?
AB - PURPOSE: To examine the association between myocardial fat, a poorly understood
finding frequently observed on non-contrast CT, and all-cause mortality in
patients with and without a history of prior MI. MATERIALS AND METHODS: A
retrospective cohort from a diverse urban academic center was derived from
chronic myocardial infarction (MI) patients (n = 265) and three age-matched
patients without MI (n = 690) who underwent non-contrast chest CT between 1
January 2005-31 December 2008. CT images were reviewed for left and right
ventricular fat. Electronic records identified clinical variables. Kaplan-Meier
and Cox proportional hazard analyses assessed the association between myocardial
fat and all-cause mortality. The net reclassification improvement assessed the
utility of adding myocardial fat to traditional risk prediction models. RESULTS:
Mortality was 40.1% for the no MI and 71.7% for the MI groups (median follow-up,
6.8 years; mean age, 73.7 +/- 10.6 years). In the no MI group, 25.7% had LV and
49.9% RV fat. In the MI group, 32.8% had LV and 42.3% RV fat. LV and RV fat was
highly associated (OR 5.3, p < 0.001). Ventricular fat was not associated with
cardiovascular risk factors. Myocardial fat was associated with a reduction in
the adjusted hazard of death for both the no MI (25%, p = 0.04) and the MI group
(31%, p = 0.018). Myocardial fat resulted in the correct reclassification of 22%
for the no MI group versus the Charlson score or calcium score (p = 0.004) and
47% for the MI group versus the Charlson score (p = 0.0006). CONCLUSIONS:
Patients with myocardial fat have better survival, regardless of MI status,
suggesting that myocardial fat is a beneficial biomarker and may improve risk
stratification. KEY POINTS: * Myocardial fat is commonly found on chest CT, yet
is poorly understood * Myocardial fat is associated with better survival in
patients with and without prior MI and is not associated with traditional
cardiovascular risk factors * This finding may provide clinically meaningful
prognostic value in the risk stratification of patients.
PMID- 29948082
TI - 3D-printed heart model to guide LAA closure: useful in clinical practice?
AB - OBJECTIVES: Correct device sizing for left atrial appendage (LAA) closure remains
challenging due to complex LAA shapes. The aim of our study was to investigative
the utility of personalized 3D-printed models (P3DPM) of the LAA to guide device
size selection. METHODS: Fifteen patients (75.4 +/-8.5years) scheduled for LAA
closure using an Amulet device underwent cardiac computed tomography (CT). The
LAA was segmented by semiautomatic algorithms using Vitrea(r) software. A 1.5-mm
LAA thick shell was exported in stereolithography format and printed using
TangoPlus flexible material. Different Amulet device sizes on the P3DPM were
tested. New P3DPM-CT with the device was acquired in order to appreciate the
proximal disc sealing the LAA ostium and the compression of the distal lobe
within the LAA. We predicted the device size with P3DPM and compared this with
the device sizes predicted by transesophageal echocardiography (TEE) and CT as
well as the device size implanted in patients. RESULTS: The device size predicted
by 3D-TEE and CT corresponded to the implanted device size in 8/15 (53%) and
10/15 (67%), respectively. The predicted device size from the P3DPM was accurate
in all patients, obtaining perfect contact with the LAA wall, without device
instability or excessive compression. P3DPM-CT with the deployed device showed
device deformation and positioning of the disk in relation to the pulmonary
veins, allowing us to determine the best device size in all 15 cases. CONCLUSION:
P3DPM allowed us to simulate the LAA closure procedure and thus helped to
identify the best Amulet size and position within the LAA. KEY POINTS: * A 3D
printed heart model allows to simulate the LAA closure procedure. * A 3D-printed
heart model allowed to identify the optimal Amulet size and position. * 3D
printed heart models may contribute to reduce the Amulet implantation learning
curve.
PMID- 29948083
TI - Analysis of errors made on in utero MR studies of the foetal brain in the
MERIDIAN study.
AB - OBJECTIVES: In utero magnetic resonance (iuMR) imaging to diagnose foetal brain
abnormalities has been established and is supported by meta-analyses of
retrospective and prospective studies. In this paper we describe and classify the
iuMR errors made in the largest diagnostic accuracy study to date (MERIDIAN). We
also correlate the error rates and types with the prior experience of the
reporting radiologists in order to inform how to provide a national programme
with the best diagnostic accuracy achievable. METHODS: The MERIDIAN cohort of 570
foetus formed the basis of this study and included 40 cases with a confirmed
diagnostic error, compared with the Outcome Reference Diagnosis. Analysis
included the potential clinical effect of the error and classification of error
type through an Expert Neuroradiological Panel re-reporting the study.
Assessments were made regarding radiologists experience prior to MERIDIAN.
RESULTS: The overall confirmed error rate for iuMR was 7.0% and it was considered
that there would have been an adverse effect on prognostic information in 22/40
cases if the iuMR had informed counselling. The experienced central reporter made
statistically significant fewer errors than the less experienced non-central
reporters (3.8% v 11.0%) and the central reporter made fewer clinically
significant errors. Furthermore, the type of cognitive errors differed between
central and non-central reporters. CONCLUSIONS: Although iuMR imaging improves
the diagnostic accuracy of detecting foetal brain abnormalities there remains a
substantial error rate, which can have major clinical significance. We have shown
that error rates are lower for more experienced reporting radiologists with fewer
potential deleterious clinical implications. We discuss the implications of these
findings in terms of providing a uniform national service. KEY POINTS: * Overall
confirmed error rate for iuMR diagnosing foetal brain abnormalities was 7.0%. *
IuMR reports had an adverse effect on counselling in 55% of error cases. * Error
rates are consistently lower for more experienced radiologists. * Collaboration
between radiologists, dual reporting, overseeing scan and formal training can
reduce errors.
PMID- 29948084
TI - Whole-body MRI for staging and interim response monitoring in paediatric and
adolescent Hodgkin's lymphoma: a comparison with multi-modality reference
standard including 18F-FDG-PET-CT.
AB - OBJECTIVES: To prospectively investigate concordance between whole-body MRI (WB
MRI) and a composite reference standard for initial staging and interim response
evaluation in paediatric and adolescent Hodgkin's lymphoma. METHODS: Fifty
patients (32 male, age range 6-19 years) underwent WB-MRI and standard
investigations, including 18F-FDG-PET-CT at diagnosis and following 2-3
chemotherapy cycles. Two radiologists in consensus interpreted WB-MRI using
prespecified definitions of disease positivity. A third radiologist reviewed a
subset of staging WB-MRIs (n = 38) separately to test for interobserver
agreement. A multidisciplinary team derived a primary reference standard using
all available imaging/clinical investigations. Subsequently, a second
multidisciplinary panel rereviewed all imaging with long-term follow-up data to
derive an enhanced reference standard. Interobserver agreement for WB-MRI reads
was tested using kappa statistics. Concordance for correct classification of all
disease sites, true positive rate (TPR), false positive rate (FPR) and kappa for
staging/response agreement were calculated for WB-MRI. RESULTS: There was
discordance for full stage in 74% (95% CI 61.9-83.9%) and 44% (32.0-56.6%) of
patients against the primary and enhanced reference standards, respectively.
Against the enhanced reference standard, the WB-MRI TPR, FPR and kappa were 91%,
1% and 0.93 (0.90-0.96) for nodal disease and 79%, < 1% and 0.86 (0.77-0.95) for
extra-nodal disease. WB-MRI response classification was correct in 25/38
evaluable patients (66%), underestimating response in 26% (kappa 0.30, 95% CI
0.04-0.57). There was a good agreement for nodal (kappa 0.78, 95% CI 0.73-0.84)
and extra-nodal staging (kappa 0.60, 95% CI 0.41-0.78) between WB-MRI reads
CONCLUSIONS: WB-MRI has reasonable accuracy for nodal and extra-nodal staging but
is discordant with standard imaging in a substantial minority of patients, and
tends to underestimate disease response. KEY POINTS: * This prospective single
centre study showed discordance for full patient staging of 44% between WB-MRI
and a multi-modality reference standard in paediatric and adolescent Hodgkin's
lymphoma. * WB-MRI underestimates interim disease response in paediatric and
adolescent Hodgkin's lymphoma. * WB-MRI shows promise in paediatric and
adolescent Hodgkin's lymphoma but currently cannot replace conventional staging
pathways including 18 F-FDG-PET-CT.
PMID- 29948085
TI - Response to Letter to the Editor on 'Piriformis muscle syndrome: A cross
sectional imaging study in 116 patients and evaluation of therapeutic outcome'.
PMID- 29948086
TI - Risk of pleural recurrence after percutaneous transthoracic needle biopsy in
stage I non-small-cell lung cancer.
AB - OBJECTIVES: To determine whether percutaneous transthoracic needle biopsy (PTNB)
increased the risk of pleural recurrence in stage I non-small-cell lung cancer
(NSCLC). METHODS: In this retrospective study, we reviewed 830 consecutive
patients with stage I NSCLC who underwent curative resection between 2004 and
2010. Cox regression analyses with propensity score matching were performed to
identify risk factors for pleural recurrence. RESULTS: Of 830 patients, 540
(65.1%) underwent PTNB before surgery, while 290 (34.9%) underwent preoperative
bronchoscopic biopsy or intraoperative wedge resection for a pathological
diagnosis. Concomitant pleural recurrence occurred in 42 patients (5.1% [95% CI,
3.8-6.8]; 34 [6.3%] PTNB patients and eight [2.8%] non-PTNB patients) and
isolated pleural recurrence took place in 26 patients (3.1% [95% CI, 2.1-4.6]; 20
[3.7%] PTNB patients and 6 [2.1%] non-PTNB patients). On multivariate analysis
after matching, only visceral pleural invasion was associated with concomitant
pleural recurrence (hazard ratio [HR]=3.367; 95% CI, 1.262-8.986; p=0.015) and
isolated pleural recurrence (HR=3.216; 95% CI, 1.037-9.978; p=0.043), while PTNB
was associated with neither concomitant nor isolated pleural recurrence (p=0.605
and p=0.963, respectively). Among 540 patients undergoing PTNB, the transfissural
approach did not have a significant association with pleural recurrence (p=0.539
and p=0.313, respectively); instead, visceral pleural invasion and microscopic
lymphatic invasion were significantly associated with concomitant pleural
recurrence, and microscopic lymphatic invasion was associated with isolated
pleural recurrence (p<0.05). CONCLUSION: PTNB did not significantly increase the
risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion
was responsible for pleural recurrence. KEY POINTS: * PTNB did not significantly
increase the risk of pleural recurrence in stage I NSCLC, whereas visceral
pleural invasion was responsible for pleural recurrence. * The transfissural
approach in PTNB did not increase the risk of pleural recurrence. * PTNB can be
performed for the confirmatory diagnosis of peripheral stage I lung cancer
without concern for the risk of pleural recurrence.
PMID- 29948087
TI - Suspicion of appendicitis in pregnant women: emergency evaluation by sonography
and low-dose CT with oral contrast.
AB - OBJECTIVES: To evaluate non-intravenously enhanced low-dose computed tomography
with oral contrast (LDCT) for the assessment of pregnant women with right lower
quadrant pain, when magnetic resonance imaging (MRI) is not immediately
available. METHODS: One hundred and thirty-eight consecutive pregnant women with
acute abdominal pain were admitted in our emergency centre. Thirty-seven (27%) of
them, with clinical suspicion of acute appendicitis, underwent abdominal
ultrasonography (US). No further examination was recommended when US was positive
for appendicitis, negative with low clinical suspicion or showed an alternative
diagnosis which explained the clinical presentation. All other patients underwent
LDCT (<2.5 mSv). Standard intravenously enhanced CT or MRI was performed when
LDCT was indeterminate. RESULTS: Eight (22%) of 37 US exams were reported normal,
25 (67%) indeterminate, 1 (3%) positive for appendicitis, 3 (8%) positive for an
alternative diagnosis. LDCT was obtained in 29 (78%) patients. It was reported
positive for appendicitis in 9 (31%), for alternative diagnosis in 2 (7%), normal
in 13 (45%) and indeterminate in 5 (17%). Further imaging (standard CT or MRI)
showed appendicitis in 2 of these 5 patients, was truly negative in 1,
indeterminate in 1 and falsely positive in 1. An appendicitis was confirmed at
surgery in 12 (32%) of the 37 patients. The sensitivity and the specificity of
the algorithm for appendicitis were 100% (12/12) and 92% (23/25), respectively.
CONCLUSIONS: The proposed algorithm is very sensitive and specific for detection
of acute appendicitis in pregnant women; it reduces the need of standard CTs when
MRI is not available as second-line imaging. KEY POINTS: * In pregnant women, US
is limited by an important number of indeterminate results * Low-dose CT can be
used after an inconclusive US for the diagnosis of appendicitis in pregnant women
* An algorithm integrating US and low-dose CT is highly sensitive and specific
for appendicitis in pregnant women.
PMID- 29948088
TI - Single-source dual-energy computed tomography for the assessment of bone marrow
oedema in vertebral compression fractures: a prospective diagnostic accuracy
study.
AB - OBJECTIVES: To evaluate the diagnostic accuracy of single-source dual-energy
computed tomography (DECT) for the detection of bone marrow oedema (BME) in
patients with vertebral compression fractures. METHODS: Patients over 50 years of
age with radiographically suspected vertebral compression fracture of the
thoracic or lumbar spine were prospectively enrolled. All patients underwent DECT
with sequential acquisition of 80 and 135 kVp datasets on a 320-row detector CT
scanner and 1.5-Tesla magnetic resonance imaging (MRI) including T1-weighted and
short-tau inversion recovery (STIR) sequences. Virtual non-calcium (VNCa) images
were reconstructed using a three-material decomposition algorithm. Vertebrae with
height loss in CT were scored for the presence of BME in both MRI and DECT and
used to determine signal- and contrast-to-noise ratios (SNR and CNR). Contingency
analysis using MRI as standard of reference and Fleiss's kappa were calculated.
IRB approval was obtained. RESULTS: In total 192 vertebral compression fractures
in 70 patients (23 men, 47 women; mean age 70.7 years (SD 9.8)) were included in
our analysis. DECT showed a reader-dependent sensitivity of 72% and specificity
of 70% for BME. Fleiss's kappa was .40 for DECT and .58 for MRI. T1-weighted
images had significantly better SNR and CNR compared to STIR, CT, and VNCa (p <
.0001); however, there was no difference between STIR and VNCa. CONCLUSIONS: VNCa
images depict BME with adequate sensitivity and specificity and can be acquired
on a single-source system. Image quality is adequate but trained readers are
needed for image interpretation. KEY POINTS: * Dual-energy CT in a single-source
technique can help to detect bone marrow oedema in patients with vertebral
compression fractures. * However, given the inferior inter-rater reliability and
limited specificity compared to MRI, experienced readers are needed for image
interpretation. * Dual-energy CT of the spine has limited sensitivity for the
detection of bone marrow oedema in vertebra with previous surgical intervention.
PMID- 29948089
TI - A cloud-based computer-aided detection system improves identification of lung
nodules on computed tomography scans of patients with extra-thoracic
malignancies.
AB - OBJECTIVES: To compare unassisted and CAD-assisted detection and time efficiency
of radiologists in reporting lung nodules on CT scans taken from patients with
extra-thoracic malignancies using a Cloud-based system. MATERIALS AND METHODS:
Three radiologists searched for pulmonary nodules in patients with extra-thoracic
malignancy who underwent CT (slice thickness/spacing 2 mm/1.7 mm) between
September 2015 and March 2016. All nodules detected by unassisted reading were
measured and coordinates were uploaded on a cloud-based system. CAD marks were
then reviewed by the same readers using the cloud-based interface. To establish
the reference standard all nodules >= 3 mm detected by at least one radiologist
were validated by two additional experienced radiologists in consensus. Reader
detection rate and reporting time with and without CAD were compared. The study
was approved by the local ethics committee. All patients signed written informed
consent. RESULTS: The series included 225 patients (age range 21-90 years, mean
62 years), including 75 patients having at least one nodule, for a total of 215
nodules. Stand-alone CAD sensitivity for lesions >= 3 mm was 85% (183/215, 95%
CI: 82-91); mean false-positive rate per scan was 3.8. Sensitivity across readers
in detecting lesions >= 3 mm was statistically higher using CAD: 65% (95% CI: 61
69) versus 88% (95% CI: 86-91, p<0.01). Reading time increased by 11% using CAD
(296 s vs. 329 s; p<0.05). CONCLUSION: In patients with extra-thoracic
malignancies, CAD-assisted reading improves detection of >= 3-mm lung nodules on
CT, slightly increasing reading time. KEY POINTS: * CAD-assisted reading improves
the detection of lung nodules compared with unassisted reading on CT scans of
patients with primary extra-thoracic tumour, slightly increasing reading time. *
Cloud-based CAD systems may represent a cost-effective solution since CAD results
can be reviewed while a separated cloud back-end is taking care of computations.
* Early identification of lung nodules by CAD-assisted interpretation of CT scans
in patients with extra-thoracic primary tumours is of paramount importance as it
could anticipate surgery and extend patient life expectancy.
PMID- 29948090
TI - A New Model for MR Evaluation of Liver Function with Gadoxetic Acid, Including
Both Uptake and Excretion.
AB - OBJECTIVES: Most existing models that are in use to model hepatic function
through assessment of hepatic gadoxetic acid enhancement kinetics do not consider
quantitative measures of gadoxetic excretion. We developed a model that allows a
simultaneous quantitation of uptake and excretion of liver specific contrast
agents. The aim was to improve the assessment of hepatic synthetic function, and
provide quantitative measures of hepatic excretion function. METHODS: Sixteen
patients underwent dynamic T1-weighted turbo gradient echo imaging at 1.5 T prior
and after bolus injection of gadoxetic acid at 0.1 ml/kg. DCE-images were
obtained for 30 min after injection. A dual-inlet two-compartment model was then
used to fit the measured liver signal values. Four tissue parameters
(extracellular volume fraction, arterial flow fraction, uptake rate and excretion
half-time) were extracted for each liver segment. RESULTS: The proposed model
provided a good fit to acquired data. Mean values for arterial flow fraction
(0.08+-0.04), extracellular volume (0.20+/-0.08) and uptake rate (4.02 +/-1.32
/100 ml/min) were comparable to those obtained with the conventional model
(0.08+/-0.05, 0.21+/-0.12, and 4.93+/-1.74), but exhibited significantly less
variation and improved fit quality. CONCLUSIONS: The proposed model is more
accurate than existing conventional models and provides an additional excretion
parameter. KEY POINTS: * Models of hepatic contrast agent uptake can be extended
to include excretion. * Including an additional excretion parameter improves
accuracy of the model. * Standard diagnostic sequences can be extended to
incorporate the model.
PMID- 29948092
TI - Breast Pocket Irrigation with Antibiotic Solution at Implant Insertion: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Antibiotic irrigation is routinely used during implant insertion in
augmentation mammoplasty procedures. However, the evidence for whether this
reduces the incidence of infection or capsular contracture is unclear. METHODS
AND MATERIALS: Five databases were used to search for all randomized control
trials, retrospective cohort and prospective cohort studies containing original
data related to the primary outcomes being investigated in this study. The
primary outcomes were the effects of antibiotic breast pocket irrigation on
clinical infection and capsular contracture. The literature search was designed
to combine three concepts: implant or tissue expander-based breast surgery,
antibiotic irrigation and clinical infection or capsular contracture. Studies
found were screened using specific eligibility criteria. Risk ratios (RR) and 95%
confidence interval (CI) were calculated using pooled acquired data from all
included studies. RESULTS: The search identified 1256 citations. Three
independent screeners identified seven studies that met the inclusion criteria
with a pooled population of 4725. This included one prospective and six
retrospective studies. A meta-analysis of pooled study data showed significant
reductions in clinical infection (RR 0.52, 95% CI 0.33-0.81) and capsular
contracture (RR 0.36, 95% CI 0.16-0.83) as a result of antibiotic irrigation.
CONCLUSION: The meta-analyses support the use of antibiotic irrigation of the
breast pocket. However, the results of this study are limited by the large
proportion of retrospective studies, the small number of studies included, the
lack of randomized controlled trials and the heterogeneity of the antibiotic and
control regimes used. LEVEL OF EVIDENCE III: This journal requires that authors
assign a level of evidence to each article. For a full description of these
Evidence-Based Medicine ratings, please refer to the Table of Contents or the
online Instructions to Authors www.springer.com/00266 .
PMID- 29948091
TI - Vaccine adjuvants CpG (oligodeoxynucleotides ODNs), MPL (3-O-deacylated
monophosphoryl lipid A) and naloxone-enhanced Th1 immune response to the
Plasmodium vivax recombinant thrombospondin-related adhesive protein (TRAP) in
mice.
AB - Despite considerable efforts toward vaccine development over decades, there is no
available effective vaccine against Plasmodium vivax. Thrombospondin-related
adhesive protein of P. vivax (PvTRAP) is essential for sporozoite motility and
invasions into mosquito's salivary gland and vertebrate's hepatocyte; hence, it
is a promising target for pre-erythrocytic vaccine. In the current investigation,
the role of antibodies and cellular immune responses induced by purified
recombinant PvTRAP (rPvTRAP) delivered in three adjuvants, naloxone (NLX), CpG
oligodeoxynucleotides ODN1826 (CpG-ODN), and 3-O-deacylated monophosphoryl lipid
A (MPL), alone and in combination was evaluated in immunized C57BL/6 mice. The
highest level and the avidity of anti-PvTRAP IgG (mean OD490nm 2.55), IgG2b (mean
OD490nm 1.68), and IgG2c (mean OD490nm 1.466) were identified in the group
received rPvTRA/NLX-MPL-CpG. This group also presented the highest IgG2c/IgG1
(2.58) and IgG2b/IgG1 (2.95) ratio when compared to all other groups, and among
the adjuvant groups, the lowest IgG2c/IgG1 (1.86) and IgG2b/IgG1 (2.25) ratio was
observed in mice receiving rPvTRAP/NLX. Mice receiving rPvTRAP/adjuvants induced
significantly the higher levels of interferon gamma (IFN-gamma), low level of
detectable IL-10, and no detectable IL-4 production. The present result revealed
that PvTRAP is immunogenic and its administration with CPG, MPL, and NLX in
C57BL/6 mice induced Th1 immune response. Besides, the rPvTRAP delivery in the
mixed formulation of those adjuvants had more potential to increase the level,
avidity, and persistence of anti-TRAP antibodies. However, it warrants further
assessment to test the blocking activity of the produced antibodies in immunized
mice with different adjuvant formulations.
PMID- 29948093
TI - Reply to the Editor Regarding: Magnusson MR, Deva AK Letter to the Editor 2018
May 2 in Relation to: Fleming D, Stone J, Tansley P. Spontaneous Regression and
Resolution of Breast Implant-Associated Anaplastic Large Cell Lymphoma:
Implications for Research, Diagnosis and Clinical Management. Aesth Plast Surg,
2018.
PMID- 29948095
TI - Body Image, Personality Traits, and Quality of Life in Botulinum Toxin A and
Dermal Filler Patients.
AB - BACKGROUND: The demand for minimally invasive cosmetic procedures has continued
to rise, especially in Germany, yet few studies have examined this patient
population. The literature in Germany has repeatedly voiced the speculation that
users of minimally invasive, skin-rejuvenating procedures displayed a higher
tendency toward dysmorphic behavior patterns or, respectively, other abnormal
personality traits. OBJECTIVES: The aim of this study was to investigate body
image, personality traits, quality of life, and socioeconomic parameters in users
of botulinum toxin and/or facial fillers. METHODS: One hundred forty-five females
presented for botulinum toxin and/or soft tissue filler injections completed
demographic and standardized psychometric questionnaires such as the World-Health
Organization Quality of Life-Short Form, Big Five Inventory-10, Body Dysmorphic
Disorder Questionnaire before treatment. RESULTS: Patients undergoing injectable
aesthetic treatments in an urban dermatology practice were women, middle-aged,
highly educated, and mostly employed. Furthermore, participants showed higher
quality of life, especially health-related quality of life, and a lower body mass
index than controls. Concerning personality traits, our participants scored
significantly higher on extraversion, agreeableness, openness to experience, and
neuroticism. CONCLUSIONS: This study helps to better understand the psychosocial
factors characterizing this patient population. Patients differ from controls by
having a higher level of quality of life. No signs of body dysmorphic patterns or
problematic personality traits were found. LEVEL OF EVIDENCE IV: This journal
requires that authors assign a level of evidence to each article. For a full
description of these Evidence-Based Medicine ratings, please refer to the Table
of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID- 29948096
TI - Successful Management of Infected Facial Filler with Brucella.
AB - BACKGROUND: The widespread desire to maintain youth and beauty with minimally
invasive procedures made the use of soft tissue fillers an attractive option to
correct numerous aesthetic problems. However, many complications have emerged
recently especially with the use of non-FDA-approved permanent materials. In this
case report, we are demonstrating the effective management of a patient with
Brucella isolated from a facial abscess at the site of prior permanent filler
injection done 17 years ago. METHODS: A 56-year-old woman presented complaining
of painful swelling of the right cheek after a failed trial of filler evacuation
and intralesional corticosteroid injection. The patient was interviewed
carefully, and physical examination was performed, followed by culture and
imaging. RESULTS: The patient had a facial abscess that was complicated by
parotid infiltration by Brucella. Eventually she was managed successfully by anti
Brucella antibiotics for 6 months with no further complaints. A review of
causative organisms in the literature along with recommendations for management
is discussed. CONCLUSION: Permanent fillers have shown many complications that
can occur even years after injection. Therefore, physicians should be careful
when using permanent fillers and should restrict their use to certain situations.
Moreover, rare infections must be kept in mind and careful history, including
travel history and animal contact, needs to be considered particularly in the
unusual scenarios. LEVEL OF EVIDENCE V: This journal requires that authors assign
a level of evidence to each article. For a full description of these Evidence
Based Medicine ratings, please refer to the Table of Contents or the online
Instructions to Authors www.springer.com/00266 .
PMID- 29948094
TI - Breast-Conserving Surgery with Immediate Autologous Fat Grafting Reconstruction:
Oncologic Outcomes.
AB - INTRODUCTION: Autologous fat grafting (AFG; lipofilling, lipografting) has been
used in delayed breast reconstruction. Recently, it has also been investigated as
an alternative for immediate reconstruction in patients submitted to breast
conserving surgery (BCS). Although good aesthetic results have been reported, the
oncologic safety of the procedure remains under investigation. This article aims
to assess oncologic outcomes of patients submitted to BCS with immediate AFG
reconstruction. METHODS: This study consisted of 65 patients undergoing BCS with
AFG between January 2010 and January 2017. They were closely followed after
surgery for a median period of 40.8 months. Locoregional and systemic recurrences
were the primary endpoints of this study. RESULTS: Ten patients developed cancer
recurrence (15.4%). The median time for recurrence was 58.9 months. Only two
patients presented locoregional recurrence (LRR) (3.07%). Five patients had
systemic recurrence (7.69%), and three had both systemic and LRR (4.61%). Median
disease-free survival (DFS) was 42.2 months, and overall survival (OV) was 44.3
months. Recurrences were significantly associated with the number of metastatic
axillary lymph nodes detected. CONCLUSION: Oncologic outcomes of immediate AFG
are similar to the results previously reported in BCS without AFG. Locoregional
and systemic recurrences are associated with the presence of axillary metastases.
LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of
evidence to each article. For a full description of these Evidence-Based Medicine
ratings, please refer to the Table of Contents or the online Instructions to
Authors www.springer.com/00266 .
PMID- 29948097
TI - Age-Related Changes in the External Noses of the Anatolian Men.
AB - OBJECTIVE: Knowledge of age-related nasal region measurements in Anatolian men;
growth changes between adult and old age. BACKGROUND: The nose plays a critical
role in determining the external appearance of an individual. Craniofacial
anthropometry has been commonly used in forensic anthropology and medicine.
METHODS: A total of 300 men (100 between 20-40 years; 100 between 40-60 years and
100 60-up years) were measured using a photographic technic from the Image J
program. From the landmarks, 13 linear distances and 3 angles were calculated and
averaged for age groups. RESULTS: The means of nasal bridge lengths of three age
groups were 60.30, 63.43 and 64.63 mm, respectively. The average nasal tip
protrusions of three groups were 24.31, 26.69 and 27.53 mm, respectively.
Nasolabial angle, nasal bridge length and tip protrusion, anatomic and
morphologic nose width and root width were statistically different between the
three age groups (p < 0.05). CONCLUSION: Results collected in this study could
serve as a data bank for nasal anthropometry during aging and development. The
assessment of teratogenic-induced traumas, craniofacial alteration, facial
reconstruction, aging of dead person and personal identification may be assisted
by age data from Anatolian men from age data banks. LEVEL OF EVIDENCE III: This
journal requires that authors assign a level of evidence to each article. For a
full description of these Evidence-Based Medicine ratings, please refer to Table
of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID- 29948098
TI - Degree of Acceptance of Breast Reconstruction and the Associated Factors Among a
Population of Chinese Women with Breast Cancer.
AB - BACKGROUND: Breast cancer is one of the most common female "malignancies"
reported worldwide in recent years. This study is aimed to understand the degree
of acceptance of breast reconstruction among breast cancer patients in Chinese
women and to explore the related factors. METHODS: Breast cancer patients were
asked to fill in the demographic questionnaire, and consent for evaluation of
Breast Reconstruction Acceptance Scale, Social Support Scale, and Functional
Assessment of Cancer Therapy-breast Quality of Life Instrument (FACT-B). The data
were assessed using multivariate logistic regression analysis for the
correlations between the degree of acceptance of breast reconstruction and age,
marital status, family monthly income, quality of life, and social support.
RESULTS: 57.5% of 715 patients were not familiar with breast reconstruction.
Results showed correlation with the degree of acceptance of breast
reconstruction. Multivariate analysis indicated that age (41-50 years old, OR:
0.25, 95% CI: 0.08-0.76; > 50, OR: 0.05, 95% CI: 0.02-0.15), marital status
(married, OR: 0.15, 95% CI: 0.05-0.43; divorced/widowed, OR: 0.11, 95% CI: 0.03
0.42), family income (3-10 thousand RMB, OR: 2.01, 95% CI: 1.08-3.76; > 10
thousand RMB, OR: 2.14, 95% CI: 1.05-4.37), quality of life (fair, OR: 0.59, 95%
CI: 0.39-0.91), and social support (excellent, OR: 0.50, 95% CI: 0.30-0.83) were
all correlated with the degree of acceptance of breast reconstruction.
CONCLUSION: Chinese breast cancer patients have a low degree of acceptance of
breast reconstruction. The degree of acceptance was found to be correlated with
age, marital status, family monthly income, quality of life, and social support.
LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of
evidence to each article. For a full description of these Evidence-Based Medicine
ratings, please refer to the Table of Contents or the online Instructions to
Authors www.springer.com/00266 .
PMID- 29948099
TI - Patient-Reported Satisfaction Following Post-bariatric Surgery: A Systematic
Review.
AB - INTRODUCTION: The aims of our study were to identify studies that evaluated
patient satisfaction following post-bariatric surgery, analyse existing
questionnaires, and summarise their development, psychometric properties, and
content. PATIENTS AND METHODS: A multistep search was undertaken on the web-based
PubMed database from the National Library of Medicine to identify studies on
patient satisfaction and quality of life following post-bariatric surgery. The
authors summarised all the questionnaires used in every study and categorised
them as generic, surgery specific, or ad hoc, and whether they contained either
validated or unvalidated measures. RESULTS: Our search generated a total of 1754
articles. We performed a systematic review of the 12 remaining studies, because
these had sufficient data and met the inclusion criteria. All the studies
identified from the literature review were assessed to determine the type of
surgery used, and whether or not the questionnaire used to analyse patient
satisfaction had been validated. The questionnaires were analysed by reviewers to
assess adherence to the rules of the US Food and Drug Administration and the
Scientific Advisory Committee of the Medical Outcomes Trust. We identified 20
individual questionnaires that included 10 generic instruments that assessed
quality of life, six instruments specific for post-bariatric surgery, three
instruments specific for breast surgery. CONCLUSIONS: In post-bariatric patients,
the BODY-Q was shown to be a more objective and confident measure for evaluating
the quality of life of patients following post-bariatric surgery. LEVEL OF
EVIDENCE III: For a full description of these Evidence-Based Medicine ratings,
please refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266 .
PMID- 29948100
TI - Revision Abdominoplasty with Truncal Liposculpting: A 10-Year Experience.
AB - INTRODUCTION: Abdominoplasty is one of the most popular body-contouring
procedures. Despite its popularity, classic abdominoplasty is still associated
with a significant rate of complaints from patients such as: fullness of flanks
and epigastric areas, lack of a posterior lumbar curve, hanging skin over the
incision line, and visible scars over the flanks and beyond underwear or swimming
suit coverage. This study reviews the authors' experience in redo abdominoplasty
when the patient is not or partially satisfied with the primary procedure.
PATIENTS AND METHODS: A total of 115 female and 32 male patients underwent
revision abdominoplasty with truncal liposculpting between 2007 and 2016. The age
distribution of patients ranged from 33 to 73 years, with a mean of 43.1 years.
All the patients included in the study had undergone classic abdominoplasty in a
different institution. Overall satisfaction with the body appearance after the
combined procedure was rated on a scale of 1-5, where 1 is 'poor,' 2 is 'fair,' 3
is 'good,' 4 is 'very good,' and 5 is 'excellent.' The evaluation was made 12
months after the composite body-contouring procedure. RESULTS: Four hundred to
1500 ml of fat were obtained with liposuction (mean 840 ml). The amount of clean,
adipose tissue transplanted to the buttocks varied from 95 to 425 (mean 286 ml)
and to the lower limbs from 75 to 270 ml (mean 195 ml). The stromal-enriched
lipograft technique was used in all the cases to enrich the fat transplantation.
There was no hematoma, infection or deep vein thrombosis. Seventy-five percent
reported that their appearance after composite body contouring was 'very good' to
'excellent' (30% 'excellent' and 45% 'very good') and 20% responded that their
appearance was 'good.' Only 5% of patients thought their appearance was less than
good ('fair'). The average follow-up time for this group of patients has been 6.3
years (range 1-10 years). CONCLUSION: Truncal liposculpting with modified
abdominoplasty accomplishes very good aesthetic results in a single surgical
procedure with a low rate of complications and high patient satisfaction in cases
of revision abdominoplasties. LEVEL OF EVIDENCE V: This journal requires that
authors assign a level of evidence to each article. For a full description of
these Evidence-Based Medicine ratings, please refer to Table of Contents or the
online Instructions to Authors www.springer.com/00266 .
PMID- 29948101
TI - A Nipple-Areolar Complex Reconstruction in Implant-Based Breast Reconstruction
Using a Local Flap and Full-Thickness Skin Graft.
AB - INTRODUCTION: Nipple-areolar complex reconstruction is the final step of the
reconstructive procedure in breast cancer patients. Nowadays, a combination of a
local flap for nipple reconstruction and skin grafting or tattooing for areola
reconstruction is deemed a first choice. In this paper, we are combining the
techniques of local flap and full-thickness skin graft from the upper inner thigh
for simultaneous reconstruction of the nipple and areola. PATIENTS AND METHODS:
From January, 2016 to December, 2017, 23 female patients with an absent
unilateral nipple-areolar complex due to post-oncological mastectomy and
immediate implant-based breast reconstruction were subjects of the study. On an
out-patient clinic basis, the percentage of the nipple projection loss was
calculated at the intervals of 3 , 6 and 12 months postoperatively. At the final
visit, the patient's subjective satisfaction on the reconstructed areola compared
to the normal contralateral side was evaluated using a visual analogue scale.
RESULTS: Over the course of time, the mean nipple projection loss was 20.16 +/-
12.88, 31.78 +/- 11.63 and 34.69 +/- 12.01% at 3 , 6 and 12 months
postoperatively, respectively. Patients' overall satisfaction on the grafted
areola was as follows; the largest number of patients (8 patients) had a 'good'
satisfaction 12-months postoperatively. Out of 21 patients, those who considered
the result to be 'poor' and 'disappointing' each accounted for 1 and 3 patients.
CONCLUSION: The combination of nipple-areolar complex reconstruction technique
introduced in this study has proven to be a safe and efficacious alternative in
patients with implant-based reconstruction requiring small- to medium-sized
nipple projection, especially when the skin envelope is too tight for a local
flap only. LEVEL OF EVIDENCE IV: This journal requires that authors assign a
level of evidence to each article. For a full description of these Evidence-Based
Medicine ratings, please refer to the Table of Contents or the online
Instructions to Authors www.springer.com/00266 .
PMID- 29948102
TI - Commentary On: Several Opinions on Quantifying Dynamic Deformity after Dual-Plane
Breast Augmentation.
PMID- 29948103
TI - Effectiveness and Safety of an Overnight Patch Containing Allium cepa Extract and
Allantoin for Post-Dermatologic Surgery Scars.
AB - BACKGROUND: An occlusive overnight intensive patch medical device (OIP)
containing onion extract and allantoin has been developed for preventing and
treating dermatologic scars and keloids. Here, we examined the efficacy and
safety of the OIP for post-dermatologic surgery scars. METHODS: This was an intra
individual randomized, observer-blind, controlled study in adults with post
dermatologic surgery scars. Two scars per subject were randomized to no treatment
or overnight treatment with the OIP for 12-24 weeks. Scar quality was assessed
using the Patient and Observer Scar Assessment Scale (POSAS) and a Global
Aesthetic Improvement Scale. RESULTS: A total of 125 subjects were included. The
decrease in observer-assessed POSAS from baseline was significantly greater for
treated than untreated scars at week 6 (p < 0.001) and 24 (p = 0.001). The
decrease in patient-assessed POSAS was significantly greater for the treated scar
than the untreated scar at week 12 (p = 0.017) and 24 (p = 0.014). Subject- and
investigator-evaluated Global Aesthetic Improvement Scale scores were higher for
the treated than the untreated scar at all visits. All subjects considered the
global comfort of the OIP to be good or very good, and no safety concerns were
identified. CONCLUSIONS: This study confirmed that the OIP safely promotes scar
healing after minor dermatologic surgery. LEVEL OF EVIDENCE II: This journal
requires that authors assign a level of evidence to each article. For a full
description of these Evidence-Based Medicine ratings, please refer to the Table
of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID- 29948104
TI - Breast Reduction Using the Superomedial Pedicle- and Septal Perforator-Based
Technique: Our Clinical Experience.
AB - BACKGROUND: Adequate tissue removal must be performed for symptom relief
following reduction mammoplasty. However, this is not always possible in patients
with gigantomastia because the pedicle is planned wider and the breast cannot be
sufficiently reduced to prevent compromising the blood supply to the pedicle. To
maximize blood circulation to the nipple-areola complex in our patients, the
pedicle was planned to include the internal thoracic artery branches coming from
both the second and third interspaces and the intercostal artery branches coming
from the fourth and fifth intercostal spaces. METHODS: A total of 185 patients
underwent reduction mammoplasty with the superomedial pedicle- and septal
perforator-based technique. The mean weight of excised tissue was 928.77 g from
the right breast and 899.92 g from the left, whereas the mean distance of nipple
areola transfer was 11.52 cm on the right breast and 11.27 cm on the left.
RESULTS: Complications developed in 11 patients (5.94%): hematoma occurred in
three patients, partial loss of areola and fat necrosis in five patients, and
wound dehiscence in three patients. CONCLUSIONS: The pedicle included vessels of
both superomedial and septum origin without any disruption in circulation.
Consequently, the blood supply of the nipple-areola complex was preserved.
Furthermore, in cases where the pedicle was long, intercostal perforators were
identified and the pedicle was narrowed thoroughly; thus, the breast was reduced
to the desired volume while minimizing the risk of complications. LEVEL OF
EVIDENCE IV: This journal requires that authors assign a level of evidence to
each article. For a full description of these Evidence-Based Medicine ratings,
please refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266 .
PMID- 29948105
TI - What is the prognostic impact of FDG PET in locally advanced head and neck
squamous cell carcinoma treated with concomitant chemo-radiotherapy? A systematic
review and meta-analysis.
AB - PURPOSE: Evidence is conflicting on the prognostic value of 18F
fluorodeoxyglucose (FDG) positron emission tomography (PET) in head and neck
squamous cell carcinoma. The aim of our study was to determine the impact of
semiquantitative and qualitative metabolic parameters on the outcome in patients
managed with standard treatment for locally advanced disease. METHODS: A
systematic review of the literature was conducted. A meta-analysis was performed
of studies providing estimates of relative risk (RR) for the association between
semiquantitative metabolic parameters and efficacy outcome measures. RESULTS: The
analysis included 25 studies, for a total of 2,223 subjects. The most frequent
primary tumour site was the oropharynx (1,150/2,223 patients, 51.7%). According
to the available data, the majority of patients had stage III/IV disease
(1,709/1,799, 94.9%; no information available in four studies) and were treated
with standard concurrent chemoradiotherapy (1,562/2,009 patients, 77.7%; only one
study without available information). A total of 11, 8 and 4 independent studies
provided RR estimates for the association between baseline FDG PET metrics and
overall survival (OS), progression-free survival (PFS) and locoregional control
(LRC), respectively. High pretreatment metabolic tumour volume (MTV) was
significantly associated with a worse OS (summary RR 1.86, 95% CI 1.08-3.21), PFS
(summary RR 1.81, 95% CI 1.14-2.89) and LRC (summary RR 3.49, 95% CI 1.65-7.35).
Given the large heterogeneity (I2 > 50%) affecting the summary measures, no
cumulative threshold for an unfavourable prognosis could be defined. No
statistically significant association was found between SUVmax and any of the
outcome measures. CONCLUSION: FDG PET has prognostic relevance in the context of
locally advanced head and neck squamous cell carcinoma. Pretreatment MTV is the
only metabolic variable with a significant impact on patient outcome. Because of
the heterogeneity and the lack of standardized methodology, no definitive
conclusions on optimal cut-off values can be drawn.
PMID- 29948106
TI - The role of FDG PET/CT in therapy control of aortic graft infection.
AB - PURPOSE: 18F-FDG PET/CT (PET/CT) is a useful tool for the diagnosis of aortic
graft infection (AGI), but has rarely been used to influence therapeutic
decisions during follow-up. We aimed to study the role of PET/CT in the long-term
monitoring of patients. METHODS: Participants of the prospective Vascular Graft
Infection Cohort Study (VASGRA) were included if they had microbiologically
proven AGI. We quantified the metabolic activity in PET/CT by using maximum
standardized uptake value (SUVmax) and further classified it as being focal or
diffuse. Multivariable linear regression models were fit using generalized
estimating equations to investigate factors associated with SUVmax over time.
RESULTS: Sixty-eight participants with AGI contributed to 266 PET/CTs including
36 examinations performed after stop of antimicrobial therapy. Higher C-reactive
protein (CRP) (adjusted coefficient per log10 mg/L 0.05 [95% C.I. 0.02-0.08]) was
associated with higher SUVmax. CRP, metabolic and clinical findings informed the
decision to either start (medians of SUVmax 7.1 and CRP 31.5 mg/L; 100% focal
uptake), escalate (SUVmax 9.5; CRP 31.5; 100% focal uptake), continue (SUVmax
6.0; CRP 9.95 mg/L; 90% focal uptake), or stop (SUVmax 4.3; CRP 3.5 mg/L; 61%
focal uptake) antibiotic treatment. Of note, decisions to escalate or continue
antibiotic treatment were taken despite normal CRP values in 12.5 and 35.7% of
PET/CTs, respectively. CONCLUSIONS: Consecutive PET/CTs could influence the
clinical decision-making in patients with AGI in the near future. More studies on
the use of PET/CT in case of aortic graft infection may offer the potential for
individualized treatment approaches. CLINICALTRIALS. GOV IDENTIFIER: NCT01821664.
PMID- 29948107
TI - Radioembolization with 90Y glass microspheres for hepatocellular carcinoma:
significance of pretreatment 11C-acetate and 18F-FDG PET/CT and posttreatment 90Y
PET/CT in individualized dose prescription.
AB - PURPOSE: The aim of this study was to establish an algorithm for the prescription
of 90Y glass microsphere radioembolization (90Y-GMRE) of HCC in individual
patients based on the relationship between tumour dose (TD) and response
validated by 90Y PET/CT dosimetry and dual-tracer PET/CT metabolic parameters.
METHODS: The study group comprised 62 HCC patients prospectively recruited for
90Y-GMRE who underwent pretreatment dual-tracer (11C-acetate and 18F-FDG) PET/CT
as surrogate markers of HCC cellular differentiation. Pretreatment tumour-to
nontumour ratio on 99mTc-MAA SPECT/CT (T/NTMAA) was correlated with posttreatment
90Y PET/CT T/NT90Y after quantification validation. The TD-response relationship
for HCC of different tracer groups was assessed on follow-up PET/CT 2 months
after treatment. RESULTS: 90Y PET/CT was accurate in the measurement of recovery
of injected 90Y activity (81.9-99.9%, median 94.8%). Pretreatment SPECT/CT
T/NTMAA was strongly correlated with posttreatment 90Y PET/CT T/NT90Y (5.6 +/-
3.2 versus 5.9 +/- 3.5, T/NT90Y 1.01 * T/NTMAA + 0.161, r = 0.918, P < 0.05). The
response rates were 72.4% (21/29), 70.6% (12/17) and 25% (4/16) for well,
moderately and poorly differentiated HCC, respectively. The cut-off TD for a good
response was significantly different between poorly differentiated and
well/moderately differentiated HCC (262 Gy versus 152/174 Gy) with 89.2%
sensitivity and 88% specificity. At a limiting tolerated liver dose of 70 Gy, the
T/NTMAA thresholds for predicting a good response in poorly differentiated and
well/moderately differentiated HCC were 3.5 and 2.0/2.3. Disregarding HCC
cellular differentiation, the cut-off TD became 170 Gy, with lower sensitivity
(70.3%) and specificity (76%). CONCLUSION: 90Y PET/CT can provide accurate
dosimetry for 90Y-GMRE. Pretreatment T/NTMAA predicts posttreatment T/NT90Y. The
TD thresholds for a good response are tracer-dependent, with a strong correlation
between HCC radiosensitivity and cellular differentiation and other PET-based
parameters. These cytokinetic factors improve treatment efficacy while minimizing
organ damage for the prescription of personalized 90Y-GMRE.
PMID- 29948109
TI - Polyacrylonitrile (PAN) nanofibres spun with copper nanoparticles: an anti
Escherichia coli membrane for water treatment.
AB - Copper nanoparticles (CNPs) were mixed with polyacrylonitrile (PAN) and
electrospun into nanofibres (CuPAN nanofibres). PAN nanofibres containing 1.0,
3.0 and 5.0% copper (w/v) displayed beads-on-string morphology with protrusions
of copper particles. The diameter of the CuPAN nanofibres differed according to
the copper content, ranging from 386 nm (1.0%, w/v, copper) to 922 nm (5.0%, w/v,
copper). No chemical interaction of copper with PAN was observed when studied
with X-ray diffraction, ATR-FTIR (attenuated total reflection-Fourier transform
infrared) spectroscopy and TGA (thermogravimetric analysis). None of the CuPAN
nanofibres showed signs of degradation after 7 days in water. Bacteria suspended
in random mobility buffer and filtered through a 3% CuPAN nanofibre membrane (25
mm diameter, 75-80 MUm thickness), at a filtration rate of 20 ml min-1, reduced
the cell numbers of enterotoxigenic Escherichia coli (ETEC) from 3.3 * to 2.1 *
106 cfu ml-1 and methicillin-resistant Staphylococcus aureus (MRSA) from 1.2 * 10
to 1.3 * 103 cfu ml-1. Membranes produced with 1.0, 3.0 and 5.0% (w/v) CuPAN
inhibited the growth of enteroaggregative E. coli (EAEC), enterohemorrhagic E.
coli (EHEC), enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), ETEC
and MRSA, as shown with LIVE/DEADTM BacLightTM staining. Real-time bactericidal
activity of CuPAN membranes was recorded by staining the cells with SYTO 9 and
PI, followed by flow cytometry. Filter membranes made from CuPAN fibres may be
used to reduce pathogenic E. coli cell numbers in potable water.
PMID- 29948108
TI - The roles for innate lymphoid cells in the human immune system.
AB - From constituting a novel and obscure cell population, innate lymphoid cells
(ILCs) are now accepted as a self-evident part of the immune system, contributing
with unique and complementary functions to immunity by production of effector
cytokines and interaction with other cell types. In this review, we discuss the
redundant and complementary roles of the highly plastic human ILCs and their
interaction with other immune cells with the ultimate aim of placing ILCs in a
wider context within the human immune system.
PMID- 29948110
TI - Short, auto-inducible promoters for well-controlled protein expression in
Escherichia coli.
AB - Expression of recombinant proteins in Escherichia coli often requires use of
inducible promoters to shorten the lag phase and improve protein productivity and
final protein titer. Synthetic molecules that cannot be metabolized by E. coli,
such as isopropyl thiogalactopyranoside (IPTG), have been frequently used to
trigger the protein expression during early exponential growth phase. This
practice has many drawbacks, including high cost and toxicity of IPTG, complex
operating procedure, and non-uniform protein expression pattern (some cells in
the population do not express recombinant proteins). A few auto-inducible protein
expression systems have been developed recently to overcome some of these
limitations, but they required use of an additional plasmid or presence of large
(a few kilobases) DNA part to be functional, making plasmid construction to be
difficult, especially when multiple genes need to be expressed. In this study, by
using RNA sequencing, we identified a short, endogenous promoter (PthrC) that can
be auto-induced during early exponential growth phase, and improved its
performance by use of native and mutated regulatory elements. We found that the
developed mutants of PthrC drove uniform protein expression-close to 100% of
cells were fluorescent when green fluorescence protein was used as target protein
and cells carrying them could achieve much higher cell density than those with T7
promoter (PT7), a commonly used inducible promoter. In terms of promoter strength
(product protein quantity per cell), the developed promoter mutants can cover a
range of strength, from 30 to 150% of maximal strength of PT7. One strong mutant
(PthrC3_8) was found to work well at a large range of temperature (22, 30, 37
degrees C) and in various media, and was also confirmed to cause less stress to
host cell than PT7 when they were used to express a toxic protein. We foresee
that PthrC3 and its mutants will be useful genetic parts for various applications
including metabolic engineering and biocatalysis.
PMID- 29948111
TI - Effective management of soft rot of ginger caused by Pythium spp. and Fusarium
spp.: emerging role of nanotechnology.
AB - Ginger (Zingiber officinale Rosc.) is a tropical plant cultivated all over the
world due to its culinary and medicinal properties. It is one of the most
important spices commonly used in food, which increases its commercial value.
However, soft rot (rhizome rot) is a common disease of ginger caused by fungi
such as Pythium and Fusarium spp. It is the most destructive disease of ginger,
which can reduce the production by 50 to 90%. Application of chemical fungicides
is considered as an effective method to control soft rot of ginger but extensive
use of fungicides pose serious risk to environmental and human health. Therefore,
the development of ecofriendly and economically viable alternative approaches for
effective management of soft rot of ginger such diseases is essentially required.
An acceptable approach that is being actively investigated involves
nanotechnology, which can potentially be used to control Pythium and Fusarium.
The present review is aimed to discuss worldwide status of soft rot associated
with ginger, the traditional methods available for the management of Pythium and
Fusarium spp. and most importantly, the role of various nanomaterials in the
management of soft rot of ginger. Moreover, possible antifungal mechanisms for
chemical fungicides, biological agents and nanoparticles have also been
discussed.
PMID- 29948112
TI - Polymeric solvent engineering for gram/liter scale production of a water
insoluble isoflavone derivative, (S)-equol.
AB - A potent phytoestrogen, (S)-equol, is a promising isoflavone derivative drawing
our great attention owing to its various biological and clinical benefits.
Through selective activation of the estrogen receptor ERbeta or androgen
receptor, (S)-equol reduces menopausal symptoms, osteoporosis, skin aging, hair
loss, and incidence of prostate or ovarian cancers without adverse effects.
Traditional biosynthesis of (S)-equol exploited non-productive natural equol
producing anaerobic bacteria that mainly belong to Coriobacteriaceae isolated
from human intestine. Recently, we developed a recombinant Escherichia coli
strain which could convert daidzein into (S)-equol effectively under an aerobic
condition. However, the yield was limited up to about the 200 mg/L level due to
unknown reasons. In this study, we identified that the bottleneck of the limited
production was the low solubility of isoflavone (i.e., 2.4 mg/L) in the reaction
medium. In order to solve the solubility problem without harmful effect to the
whole-cell catalyst, we applied commercial hydrophilic polymers (HPs) and a polar
aprotic co-solvent in the reaction medium. Among the examined water-soluble
polymers, polyvinylpyrrolidone (PVP)-40k was verified as the most promising
supplement which increased daidzein solubility by 40 times and (S)-equol yield up
to 1.22 g/L, the highest ever reported and the first g/L level biotransformation.
Furthermore, PVP-40k was verified to significantly increase the solubilities of
other water-insoluble natural polyphenols in aqueous solution. We suggest that
addition of both HP and polar aprotic solvent in the reaction mixture is a
powerful alternative to enhance production of polyphenolic chemicals rather than
screening appropriate organic solvents for whole-cell catalysis of polyphenols.
PMID- 29948113
TI - C-terminal Ser/Thr residues are vital for the regulatory role of Ste7 in the
asexual cycle and virulence of Beauveria bassiana.
AB - The mitogen-activated protein kinase (MAPK) kinase Ste7 has a conserved Ser/Thr
loop (S/T-X4(6)-S/T) that can activate the MAPK Fus3 or Kss1 for the regulation
of pheromone response and filamentous growth in model yeast. Here, we show that
not only the loop but also four C-terminal Ser/Thr residues are essential for
Ste7 to function in the Fus3 cascade of Beauveria bassiana, a filamentous fungal
insect pathogen. Mutagenesis of either looped S216/T220 or C-terminal S362
resulted in the same severe defects in conidial germination, hyphal growth,
aerial conidiation, and submerged blastospore production as the ste7 deletion,
followed by a complete loss of virulence and similarly increased cell
sensitivities to osmotic salts, oxidants, heat shock and UV-B irradiation.
Mutagenesis of three other Ser/Thr residues (S391, S440, and T485) also caused
severe defects in most of the mentioned phenotypes. These defects correlated well
with dramatically reduced transcript levels of some phenotype-related genes.
These genes encode a transcription factor (CreA) essential for carbon/nitrogen
assimilation, developmental activators (BrlA, AbaA, and WetA) and upstream
transcription factor (FluG) required for conidiation, P-type N+/K+ ATPases (Ena1
5) required for intracellular N+/K+ homeostasis, and antioxidant enzymes involved
in multiple stress responses. Our study unveils that the loop and four C-terminal
Ser/Thr residues are all vital for the regulatory role of Ste7 in the growth,
conidiation, virulence, and/or stress tolerance of B. bassiana and perhaps other
filamentous fungi.
PMID- 29948114
TI - Mycobacterium tuberculosis toxin Rv2872 is an RNase involved in vancomycin stress
response and biofilm development.
AB - Bacterial toxin-antitoxin (TA) systems are emerging important regulators of
multiple cellular physiological events and candidates for novel antibiotic
targets. To explore the role of Mycobacterium tuberculosis function, unknown
toxin gene Rv2872 was heterologously expressed in Mycobacterium smegmatis
(MS_Rv2872). Upon induction, MS_Rv2872 phenotype differed significantly from the
control, such as increased vancomycin resistance, retarded growth, cell wall, and
biofilm structure. This phenotype change might result from the RNase activity of
Rv2872 as purified Rv2872 toxin protein can cleave the products of several key
genes involved in abovementioned phenotypes. In summary, toxin Rv2872 was firstly
reported to be a endonuclease involved in antibiotic stress responses, cell wall
structure, and biofilm development.
PMID- 29948115
TI - A Pichia pastoris single-cell biosensor for detection of enzymatically produced
methanol.
AB - We conducted single-cell analyses of the methylotrophic yeast Pichia pastoris to
develop a biosensor for the detection of methanol produced by heterologous
enzymes. In this biosensor, methanol and its subsequent metabolism induce
expression of a gene encoding a fluorescent protein that was placed under the
control of a methanol-inducible promoter. Using quantitative analyses of
fluorescence microscopy images, a methanol-inducible promoter and a host strain
were selected, and preculture and assay conditions were optimized to improve the
methanol detection limit. Fluorescence-activated cell sorting (FACS) analysis of
the distribution and geometric mean of cellular fluorescence intensity against
various concentrations of methanol revealed a detection limit of 2.5 MUM.
Finally, this biosensor was applied to evaluate the activity of a heterologously
expressed pectin methylesterase (PME). The cellular fluorescence intensity was
proportional to the copy number of the PME expression cassette, the protein
level, and the enzyme activity. This biosensor can be used for high-throughput
screening of single cells harboring high methanol-producing activity, and
thereby, the development of a bioconversion process using methanol-producing
enzymes.
PMID- 29948116
TI - Biochemical and proteomic characterization of the extracellular enzymatic
preparate of Exiguobacterium undae, suitable for efficient animal glue removal.
AB - In this work, we describe the preparation and characterization of a biopreparate
for efficient and rapid animal glue removal. The biopreparate is based on the
extracellular proteolytic enzymes of an Exiguobacterium undae environmental
isolate. Liquid chromatography-mass spectrometry analysis showed that the
biopreparate is predominantly composed of hydrolytic enzymes-proteases and
peptidases, nucleases, peptide ABC transporter substrate-binding proteins, and a
phosphatase. The two main proteins present are bacillolysin and a peptide ABC
transporter substrate-binding protein. Inhibition and proteomic analyses of the
biopreparate revealed that bacillolysin, a neutral metalloendopeptidase, is
mainly responsible for its proteolytic activity. This biopreparate was able to
satisfactorily remove two types of animal glue from different kinds of material
surfaces. These results suggest that this biopreparate could serve as a potential
new tool for the restoration of historical objects rather than living
microorganisms.
PMID- 29948117
TI - Biochemical characterization of an ulvan lyase from the marine flavobacterium
Formosa agariphila KMM 3901T.
AB - Carbohydrates are the product of carbon dioxide fixation by algae in the ocean.
Their polysaccharides are depolymerized by marine bacteria, with a vast array of
carbohydrate-active enzymes. These enzymes are important tools to establish
biotechnological processes based on algal biomass. Green tides, which cover
coastal areas with huge amounts of algae from the genus Ulva, represent a
globally rising problem, but also an opportunity because their biomass could be
used in biorefinery processes. One major component of their cell walls is the
anionic polysaccharide ulvan for which the enzymatic depolymerization remains
largely unknown. Ulvan lyases catalyze the initial depolymerization step of this
polysaccharide, but only a few of these enzymes have been described. Here, we
report the cloning, overexpression, purification, and detailed biochemical
characterization of the endolytic ulvan lyase from Formosa agariphila KMM 3901T
which is a member of the polysaccharide lyase family PL28. The identified
biochemical parameters of the ulvan lyase reflect adaptation to the temperate
ocean where the bacterium was isolated from a macroalgal surface. The NaCl
concentration has a high influence on the turnover number of the enzyme and the
affinity to ulvan. Divalent cations were shown to be essential for enzyme
activity with Ca2+ likely being the native cofactor of the ulvan lyase. This
study contributes to the understanding of ulvan lyases, which will be useful for
future biorefinery applications of the abundant marine polysaccharide ulvan.
PMID- 29948118
TI - Analysis and validation of the pho regulon in the tacrolimus-producer strain
Streptomyces tsukubaensis: differences with the model organism Streptomyces
coelicolor.
AB - Inorganic and organic phosphate controls both primary and secondary metabolism in
Streptomyces genus. Metabolism regulation by phosphate in Streptomyces species is
mediated by the PhoR-PhoP two-component system. Response regulator PhoP binds to
conserved sequences of 11 nucleotides called direct repeat units (DRus), whose
organization and conservation determine the binding of PhoP to distinct
promoters. Streptomyces tsukubaensis is the industrial producer of the clinical
immunosuppressant tacrolimus (FK506). A bioinformatic genome analysis detected
several genes with conserved PHO boxes involved in phosphate scavenging and
transport, nitrogen regulation, and secondary metabolite production. In this
article, the PhoP regulation has been confirmed by electrophoretic mobility shift
assays (EMSA) of the most relevant members of the traditional pho regulon such as
the two-component system PhoR-P or genes involved in high-affinity phosphate
transport (pstSCAB) and low-affinity phosphate transport (pit). However, the PhoP
control over phosphatase genes in S. tsukubaensis is significantly different from
the pattern reported in the model bacteria Streptomyces coelicolor. Thus, neither
the alkaline phosphatase PhoA nor PhoD is regulated by PhoP. On the contrary, the
binding of PhoP to the promoter of a novel putative phosphatase PhoX was
confirmed. A crosstalk of the PhoP and GlnR regulators, which balances phosphate
and nitrogen utilization, also occurs in S. tsukubaensis but slightly modified.
Finally, PhoP regulates genes, like afsS, that link phosphate control and
secondary metabolite production in S. tsukubaensis. In summary, there are notable
differences between the regulation of specific genes of the pho regulon in S.
tsukubaensis and the model organism S. coelicolor.
PMID- 29948119
TI - Chlorination caused a shift in marine biofilm niches on
microfiltration/ultrafiltration and reverse osmosis membranes and UV irradiation
effectively inactivated a chlorine-resistant bacterium.
AB - The effect of chlorine disinfection on marine biofilm populations and communities
formed on membrane surfaces was investigated under two feedwater conditions: raw
seawater and deep bed filtration-treated seawater. As a result of chlorination,
the structure of the biofilm community on the microfiltration/ultrafiltration and
reverse osmosis membrane coupons shifted significantly at the genus level.
However, the total bacterial population was not reduced under the two feedwater
conditions. This failure to control the biofilm was attributed to the adaptation
and survival of selected bacteria under chlorine stress. Phaeobacter caeruleus,
isolated from the biofilm, was examined as a representative chlorine-resistant
biofilm-forming bacterium. The number of viable P. caeruleus was significantly
reduced (as much as 99.8%) after ultraviolet (UV) disinfection. The results
indicated that additional disinfection by UV irradiation can inactivate chlorine
resistant bacteria. Therefore, tandem chlorination-UV disinfection may enhance
the efficiency of biofouling control in seawater reverse osmosis processes. The
synergistic effects of tandem chlorination-UV irradiation on the marine biofilm
community should be investigated in future studies.
PMID- 29948120
TI - Temporal and spatial distribution of ammonia-oxidizing organisms of two types of
wetlands in Northeast China.
AB - Ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) contribute
significantly to the nitrogen cycle. The community structure of AOA and AOB is
diverse in the different wetlands. Few studies have comparatively investigated
the community structure and dynamics of ammonia-oxidizing organisms in the marsh
wetland (Sanjiang wetland) and inland saline-alkaline wetland (Zhalong wetland)
in Northeast China. In this study, soil samples were collected from two wetlands
with different soil properties in July and October. The community structure of
AOA and AOB based on the amoA gene was investigated by high throughput
sequencing. The result showed that AOA affiliated to the Nitrososphaera lineage
(1.1b group) were the dominant AOA in both Sanjiang and Zhalong wetlands, while
AOB belonging to the Nitrosospira lineage was the dominant AOB in the Sanjiang
wetland. AOB belonging to the Nitrosospira lineage and Nitrosomonas lineage were
the dominant AOB in the Zhalong wetland in July and October, respectively. The
dominant AOA and AOB in the Sanjiang wetland had no obvious variation from July
to October, but the AOA and AOB communities in the Zhalong wetland changed a lot
from July to October. Shannon and Simpson indexes showed the diversity of AOA in
the Zhalong wetland was higher than that in the Sanjiang wetland, but the
diversity of AOB in the Zhalong wetland was lower than that in the Sanjiang
wetland. Nitrate (NO3-) and ammonium (NH4+) concentration and pH were the most
significant factors influencing the community structure of AOA and AOB.
PMID- 29948121
TI - Identifying and engineering a critical amino acid residue to enhance the
catalytic efficiency of Pseudomonas sp. methyl parathion hydrolase.
AB - Methyl parathion hydrolase (MPH) that hydrolyzes a wide range of organophosphorus
pesticides can be used to remediate land polluted by the pesticides. Here, the
catalytic efficiency of methyl parathion hydrolase from Pseudomonas sp. (WBC-3)
was enhanced by searching and engineering a critical site far away from the
binding pocket. In the first round, a four-site mutant with a modest increased
catalytic efficiency (3.2-fold kcat/Km value of the wild type) was obtained with
random mutagenesis. By splitting and re-combining the four substitutions in the
mutant, the critical site S277, was identified to show the most significant
effects of improving binding affinity and catalytic efficiency. With further site
saturation mutagenesis focused on the residue S277, another two substitutions
were discovered to have even more significant decrease in Km (40.2 and 47.6 MUM)
and increased in kcat/Km values (9.5- and 10.3-fold of the wild type) compared to
the original four-site mutant (3.0- and 3.2-fold). In the three-dimensional
structure, residue S277 is located at a hinge region of a loop, which could act
as a "lid" at the substrate entering to the binding pocket. This suggests that
substitutions of residue S277 could affect substrate binding via conformational
change in substrate entrance region. This work provides a valuable protocol
combining random mutagenesis, site-saturation mutagenesis, structural and
bioinformatics analyses to obtain mutants with high catalytic efficiency from a
screening library of a modest size (3200 strains).
PMID- 29948122
TI - Upregulating the mevalonate pathway and repressing sterol synthesis in
Saccharomyces cerevisiae enhances the production of triterpenes.
AB - Pentacyclic triterpenes are diverse plant secondary metabolites derived from the
mevalonate (MVA) pathway. Many of these molecules are potentially valuable,
particularly as pharmaceuticals, and research has focused on their production in
simpler and more amenable heterologous systems such as the yeast Saccharomyces
cerevisiae. We have developed a new heterologous platform for the production of
pentacyclic triterpenes in S. cerevisiae based on a combinatorial engineering
strategy involving the overexpression of MVA pathway genes, the knockout of
negative regulators, and the suppression of a competing pathway. Accordingly, we
overexpressed S. cerevisiae ERG13, encoding 3-hydroxy-3-methylglutaryl-coenzyme A
(HMG-CoA) synthase, and a truncated and deregulated variant of the rate-limiting
enzyme HMG-CoA reductase 1 (tHMGR). In the same engineering step, we deleted the
ROX1 gene, encoding a negative regulator of the MVA pathway and sterol
biosynthesis, resulting in a push-and-pull strategy to enhance metabolic flux
through the system. In a second step, we redirected this enhanced metabolic flux
from late sterol biosynthesis to the production of 2,3-oxidosqualene, the direct
precursor of pentacyclic triterpenes. In yeast cells transformed with a newly
isolated sequence encoding lupeol synthase from the Russian dandelion (Taraxacum
koksaghyz), we increased the yield of pentacyclic triterpenes by 127-fold and
detected not only high levels of lupeol but also a second valuable pentacyclic
triterpene product, beta-amyrin.
PMID- 29948123
TI - Roles of gamma-aminobutyric acid on salinity-responsive genes at transcriptomic
level in poplar: involving in abscisic acid and ethylene-signalling pathways.
AB - MAIN CONCLUSION: gamma-Aminobutyric acid (GABA) affected ABA and ethylene
metabolic genes and signal components in salt-treated poplar, indicating its
potential role in signal pathways of ABA and ethylene during salt stress. GABA is
a small signalling molecule that accumulates rapidly in plants exposed to various
stresses. However, the relationship between GABA and other signalling molecules,
such as hormones, remains unclear. Here, in the poplar woody plant under 200-mM
NaCl conditions, the application of low (0.25 mM) and high (10 mM) exogenous
GABA, compared to 0 mM, affected the accumulation of hydrogen peroxide and
hormones, including ABA and ethylene, in different manners. Transcriptomic
analysis demonstrated that 1025 differentially expressed genes (DEGs; |log2Ratio|
>= 1.5) were widely affected by exogenous GABA under salt stress. A clustering
analysis revealed that GABA could rescue or promote the effects of salt stress on
gene expression. Among them, 146 genes involved in six hormone-signalling
pathways were enriched, including 22 ABA- and 50 ethylene-related genes.
Quantitative expression of selected genes involved in hormone-related pathways
showed that ABA metabolic genes (ABAG, ABAH2, and ABAH4), ethylene biosynthetic
genes (ACO1, ACO2, ACO5, ACOH1, ACS1, and ACS7) and receptor genes (PYL1, PYL2,
PYL4, and PYL6) were regulated by exogenous GABA, even at a 0.1 mM level. The
production of ABA was negatively correlated with ABAH expression levels at
different GABA concentrations. The increase of endogenous GABA, resulting from
inhibitor (succinyl phosphonate) of alpha-ketoglutarate dehydrogenase, affected
the PYLs levels. Thus, GABA may be involved in ABA- and ethylene-signalling
pathways. Our data provide a better understanding of GABA's roles in the plant
responses to environmental stresses.
PMID- 29948124
TI - The combined effects of real or simulated microgravity and red-light
photoactivation on plant root meristematic cells.
AB - MAIN CONCLUSION: Red light is able to compensate for deleterious effects of
microgravity on root cell growth and proliferation. Partial gravity combined with
red light produces differential signals during the early plant development. Light
and gravity are environmental cues used by plants throughout evolution to guide
their development. We have investigated the cross-talk between phototropism and
gravitropism under altered gravity in space. The focus was on the effects on the
meristematic balance between cell growth and proliferation, which is disrupted
under microgravity in the dark. In our spaceflight experiments, seedlings of
three Arabidopsis thaliana genotypes, namely the wild type and mutants of
phytochrome A and B, were grown for 6 days, including red-light photoactivation
for the last 2 days. Apart from the microgravity and the 1g on-board control
conditions, fractional gravity (nominally 0.1g, 0.3g, and 0.5g) was created with
on-board centrifuges. In addition, a simulated microgravity (random positioning
machine, RPM) experiment was performed on ground, including both dark-grown and
photostimulated samples. Photoactivated samples in spaceflight and RPM
experiments showed an increase in the root length consistent with phototropic
response to red light, but, as gravity increased, a gradual decrease in this
response was observed. Uncoupling of cell growth and proliferation was detected
under microgravity in darkness by transcriptomic and microscopic methods, but red
light photoactivation produced a significant reversion. In contrast, the
combination of red light and partial gravity produced small but consistent
variations in the molecular markers of cell growth and proliferation, suggesting
an antagonistic effect between light and gravity signals at the early plant
development. Understanding these parameters of plant growth and development in
microgravity will be important as bioregenerative life support systems for the
colonization of the Moon and Mars.
PMID- 29948125
TI - Endophytic effects of Aspergillus oryzae on radish (Raphanus sativus) and its
herbivore, Plutella xylostella.
AB - MAIN CONCLUSION: We provide evidence that Aspergillus oryzae not only acts as an
endophyte in Raphanus sativus, but also works as a plant growth promoter and
provides some protection against its herbivore, Plutella xylostella affecting its
feeding rate, mortality and fitness parameters, thereby contributing to the pest
population suppression. Seed inoculation of radish seeds with the fungus
Aspergillus oryzae allowed its establishment as an endophyte promoting plant
growth and negatively affecting fitness parameters of its major herbivore,
diamondback moth, Plutella xylostella. Endophytic fungi may contribute to the
growth of their host plants and enhance resistance to herbivores and diseases. We
evaluated the effect of A. oryzae (Ahlburg) E. Cohn as an endophyte in radish
(Raphanus sativus L.) on growth and development of the plants themselves and
their major herbivore, the diamondback moth P. xylostella (L). A. oryzae
colonization rates in leaves were significantly higher than in roots and stems,
with a rate of 80% in leaves, 40% in stems and 20% in roots 1 week after seed
inoculation. Colonization gradually decreased in the various plant tissues, and
disappeared completely in roots, stems and leaves within 2, 5 and 7 weeks,
respectively. A. oryzae did not affect seed germination; however, it promoted
radish growth with endophytic plants attaining average heights of 116 mm compared
to 99.6 mm in the controls at the third week post-inoculation. The P. xylostella
fitness parameters, consumption, larval and pupal weights, and feeding on the
endophytic plants were significantly lower than the controls, while larval
mortality was significantly higher. Larvae fed on endophytic plants consumed 0.46
mg less leaf matter in the first week post seed inoculation and weighed 0.83 mg
less as mature 4th instars than controls. We have demonstrated that A. oryzae can
establish as an endophyte in R. sativus through seed inoculation providing some
plant growth promotion and protection against its herbivore by increasing its
mortality and negatively affecting its fitness parameters, suggesting that
adopting seed treatments with A. oryzae may be beneficial in the commercial
cultivation of radish.
PMID- 29948126
TI - Evolutionarily conserved function of the sacred lotus (Nelumbo nucifera Gaertn.)
CER2-LIKE family in very-long-chain fatty acid elongation.
AB - MAIN CONCLUSION: Identification of NnCER2 and NnCER2-LIKE from Nelumbo nucifera,
which are required for the very-long-chain fatty acid elongation, provides new
evidence that CER2 proteins are evolutionarily conserved across the eudicots.
CER2-LIKE family proteins have been described as core components of the fatty
acid elongase complex in Arabidopsis, maize, and rice, having specific function
in synthesis of the C30 to C34 fatty acyl-CoA precursors of cuticular waxes.
Little is known about the functional conservation in this gene family across
species. In this study, two CER2-LIKE family proteins, NnCER2 and NnCER2-LIKE,
were characterized from sacred lotus (Nelumbo nucifera), which is an ancient
basal eudicot. The transcriptional expression of NnCER2 and NnCER2-LIKE was found
in floating leaf blades, emergent petioles and vertical leaves, petals, and
anthers. The NnCER2 and NnCER2-LIKE proteins were localized to the endoplasmic
reticulum and nucleus. Overexpressing NnCER2 and NnCER2-LIKE in Arabidopsis led
to alteration of cuticle wax structure in inflorescence stems, and this was
associated with elevated 30, 32, and 34 carbon length wax compounds, and their
derivatives. The different substrate specificities of NnCER2 and NnCER2-LIKE were
explored using co-expression with AtCER6 in yeast cells. These findings provide
clear evidence that the function of CER2 family proteins in producing VLCFAs is
highly conserved across the eudicots.
PMID- 29948128
TI - RNA-Seq in the discovery of a sparsely expressed scent-determining monoterpene
synthase in lavender (Lavandula).
AB - MAIN CONCLUSION: Using RNA-Seq, we cloned and characterized a unique monoterpene
synthase responsible for the formation of a scent-determining S-linalool
constituent of lavender oils from Lavandula * intermedia. Several species of
Lavandula produce essential oils (EOs) consisting mainly of monoterpenes
including linalool, one of the most abundant and scent-determining oil
constituents. Although R-linalool dominates the EOs of lavenders, varying amounts
(depending on the species) of the S-linalool enantiomer can also be found in
these plants. Despite its relatively low abundance, S-linalool contributes a
sweet, pleasant scent and is an important constituent of lavender EOs. While
several terpene synthase genes including R-linalool synthase have been cloned
from lavenders many important terpene synthases including S-linalool synthase
have not been described from these plants. In this study, we employed RNA-Seq and
other complementary sequencing data to clone and functionally characterize the
sparsely expressed S-linalool synthase cDNA (LiS-LINS) from Lavandula *
intermedia. Recombinant LiS-LINS catalyzed the conversion of the universal
monoterpene precursor geranyl diphosphate to S-linalool as the sole product.
Intriguingly, LiS-LINS exhibited very low (~ 30%) sequence similarity to other
Lavandula terpene synthases, including R-linalool synthase. However, the
predicted 3D structure of this protein, including the composition and arrangement
of amino acids at the active site, is highly homologous to known terpene synthase
proteins. LiS-LINS transcripts were detected in flowers, but were much less
abundant than those corresponding to LiR-LINS, paralleling enantiomeric
composition of linalool in L. * intermedia oils. These data indicate that
production of S-linalool is at least partially controlled at the level of
transcription from LiS-LINS. The cloned LiS-LINS cDNA may be used to enhance oil
composition in lavenders and other plants through metabolic engineering.
PMID- 29948127
TI - Dicer-like and RNA-dependent RNA polymerase gene family identification and
annotation in the cultivated Solanum tuberosum and its wild relative S.
commersonii.
AB - MAIN CONCLUSION: We provide advances in DCL and RDR gene diversity in Solanaceae.
We also shed light on DCL and RDR gene expression in response to cold stress.
DICER-like (DCL) and RNA-dependent RNA polymerase (RDR) genes form the core
components to trigger small non-coding RNA (ncRNA) production. In spite of this,
little is known about the two gene families in non-model plant species. As their
genome sequences are now available, the cultivated potato (Solanum tuberosum) and
its cold-tolerant wild relative Solanum commersonii offer a valuable opportunity
to advance our understanding of the above genes. To determine the extent of
diversification and evolution of DCLs and RDRs in these species, we performed a
comparative analysis. Seven DCLs were identified in the two species, whereas
seven and six RDR genes were found in S. tuberosum and S. commersonii,
respectively. Based on phylogenetic analysis with DCLs and RDRs from several
species, we provide evidence for an increase in their number in both potato
species. We also disclosed that tandem duplications played a major role in the
evolution of these gene families in Solanaceae. DCL and RDR expression was
investigated in different tissues and under cold and virus stresses, with
divergent profiles of the tandem duplicated genes being found in different
tissues. DCL paralogs showed a contrasting expression in S. tuberosum and S.
commersonii following cold stress and virus infection. By contrast, no change in
RDR transcript activity was detected following both stresses. Overall, this study
provides the first comparative genomic analysis of the core components of the
RNAi machinery in Solanaceae and offers a scaffold for future functional analysis
of these gene families.
PMID- 29948129
TI - A new high-throughput assay for determining soluble sugar in sorghum internode
extracted juice.
AB - MAIN CONCLUSIONS: A high-throughput method combining liquid handling system and
96-well microplate pipetting format was developed for total sugar determination.
With this new method, we characterized diverse sugar accumulation in sorghum
varieties. Sweet sorghum accumulates large amounts of sucrose in its stalk and,
therefore, has emerged as one important bioenergy crop. The commonly used sugar
measurement, Brix, limits the characterization of internode variation of the
sugar concentrations due to its low throughput. Here we developed a low-cost,
high-throughput method to determine profiles of total sugars in sorghum
internodes with a liquid handling system-based sample preparation and a phenol
sulfuric acid assay in 96-well microplate format. The present method generates
results highly correlated with commonly used Brix measurements (r = 0.922). The
inter-assay coefficient of variation ranged from 4.8 to 7.6%. The present method
can reliably estimate mixed sugars composed of 80% sucrose. We characterized the
profiles of 35 sorghum accessions and identified 21 accessions with significantly
different sugar concentrations between internodes either due to dried-up
internodes or concentration differences. As a high-throughput alternative to Brix
measurements, the new method makes it possible to phenotype total sugars from
large numbers of internode samples and, therefore, will be useful for genetic and
breeding purposes.
PMID- 29948130
TI - Combined effect of nutritional status on long-term outcomes in patients with
coronary artery disease undergoing percutaneous coronary intervention.
AB - Previous studies have reported the prognostic value of objective nutritional
indices such as the Controlling Nutritional Status (CONUT) score, Geriatric
Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI). However,
the effects of these indices in patients with coronary artery disease (CAD) who
have undergone percutaneous coronary intervention (PCI) remain unclear.
Furthermore, there are insufficient data to combine these indices. A total of
1984 patients who underwent elective PCI were enrolled. The Combined Objective
Nutritional Score was determined by assigning 1 point each for high CONUT score
(3-12), low GNRI (< 98) or low PNI (< 45). Patients were grouped into normal
nutritional status (0 points), mild-to-moderate malnutrition (1-2 points) and
severe malnutrition (3 points). Incidences of all-cause death and cardiac death
were evaluated. Among the 1984 patients, 514 (25.9%) and 244 (12.3%) had mild-to
moderate and severe malnutrition, respectively. During follow-up (median 7.4
years), 293 all-cause deaths were identified, including 92 cardiac deaths. Kaplan
Meier curves showed ongoing divergence in rates of death among nutritional
statuses determined by the novel score (log rank test, p < 0.0001). Multivariate
Cox hazard analysis showed that patients with a Combined Objective Nutritional
Score of 3 showed 2.91-fold (95% confidence interval (CI) 2.10-4.00; p < 0.0001)
and 2.16-fold (95% CI 1.15-3.92; p = 0.02) increases in risk of mortality and
cardiac mortality compared with patients with a Combined Objective Nutritional
Score of 0. In conclusion, malnutrition as evaluated by the Combined Objective
Nutritional Score was significantly associated with worse long-term
cardiovascular outcomes among CAD patients who underwent PCI.
PMID- 29948131
TI - Subclinical atherosclerosis and vascular stiffness in premenopausal women:
association with NOS3 and CYBA polymorphisms.
AB - Genetic variations of genes encoding the endothelial nitric oxide synthase (eNOS)
and the NADH/NADPH oxidase system are related with atherosclerosis in the general
population, but their significance in women is not sufficiently assessed. We
investigated the potential association between the G894T polymorphism of the NOS3
gene and the C242T polymorphism of the CYBA gene with subclinical vascular
disease. Seventy (70) healthy, normally ovulating, premenopausal women were
recruited for this study. Venous blood samples were obtained for
biochemical/hormonal assessment as well as for genotyping, using real-time PCR.
Sonographically assessed indices of vascular structure and function included
carotid and femoral intima-media thickness (IMT), flow-mediated dilation (FMD),
carotid-femoral pulse-wave velocity (PWV), and augmentation index. The prevalence
of wild type, heterozygote, and homozygote genotype was 44.3% (31/70), 54.3%
(38/70), and 1.4% (1/70) for the G894T polymorphism and 38.6% (27/70), 31.4%
(22/70), and 30.0% (21/70) for the C242T polymorphism, respectively. After
multivariable adjustment, the hC242T polymorphism was a predictor of both
internal carotid IMT (b-coefficient - 0.119, p = 0.011) and combined-IMT (b
coefficient - 0.061, p = 0.015). Systolic blood pressure, lipids, and hC242T
determined values of FMD (b-coefficient - 1.604, p = 0.034). Concerning the NOS3
G894T polymorphism, carriers of the polymorphic variant had higher values of IMT
and PWV compared to the wild-type subgroup (carotid bulb-IMT and PWV,
heterozygotes/homozygotes vs wild type 0.7 +/- 0.2 vs 0.6 +/- 0.1 mm; 7.1 +/- 0.8
vs 6.6 +/- 0.7 m/s; p = 0.048 and p = 0.029, respectively). These differences,
however, were rendered non-significant in the multivariable analysis. In healthy
premenopausal women, the CYBA C242T polymorphism is an independent determinant of
endothelial function and subclinical atherosclerosis of the carotid arteries. The
NOS3 G894T polymorphic variant also correlated with atherosclerosis, an
association probably mediated by the traditional risk factors for CVD. The
relevance of these findings in the clinical setting remains to be elucidated.
PMID- 29948132
TI - Surgical anatomy of lateral recess in paediatric auditory brainstem implant
patients and its clinical correlates including grades of flocculus.
AB - INTRODUCTION: Auditory brainstem implant (ABI), a standard technique in treatment
of profound sensorineural hearing loss in patients with neurofibromatosis 2, is
now being increasingly employed in children with congenital bilateral
sensorineural hearing loss, as in Michele's deformity. A detailed knowledge of
the relevant surgical anatomy of the lateral recess and its anatomical landmarks
including the flocculus, the choroid plexus and the root entry zones of facial
vestibulocochlear and glossopharyngeal-vagus nerve complexes and their anatomical
variants is mandatory, as it is the conduit for electrode array placement. The
placement of electrode may be eased or impeded by these variations. MATERIALS AND
METHODS: Thirty-two children with congenital bilateral hearing loss underwent
surgery through retromastoid suboccipital approach for placement of auditory
brainstem implant. The preoperative anatomy was reviewed in detail during
procedure and again later in the operative videos. RESULTS: The flocculus was
classified into four grades based on its anatomy and relations. Among these,
grade II (11 children) was the commonest while grade IV (five children) was least
common. Choroid plexus was variable in size across grades of flocculus.
Difficulty in defining the anatomy was significantly more (p value = 0.003) in
the group with higher grade flocculus (grade III and IV) than in lower grade
flocculus (grade I and II). CONCLUSION: The flocculus in these patients is
classifiable into one of the four grades and the surgical nuances such as
difficulty in defining the anatomy for placement of ABI are dependent on the
characteristics exhibited by the floccular anatomy and relations.
PMID- 29948133
TI - "Childhood peripheral facial palsy".
PMID- 29948134
TI - Endoscopic ultrasonic aspiration of brain abscess.
AB - BACKGROUND: Intracerebral abscess is a rare, but very serious complication of
neonatal sepsis. Aggressive medical and surgical strategy is warranted in
patients with large abscesses. CASE REPORT: A neonate with bilateral large
frontal abscesses, caused by Serratia marcescens, was operated using a
neuroendoscope coupled with an ultrasonic aspiration device. To our knowledge,
this is the first report of such utilization of this new tool. The left abscess
was surgically drained through endoscopic aspiration using ultrasonic aspirator.
Clinical condition rapidly improved, and postoperative MRI of the brain revealed
an almost complete resolution of the left abscess. A second endoscopic procedure
was performed 1 week later, and the right abscess was endoscopically drained with
the same technique. The remaining clinical course was uneventful. DISCUSSION AND
CONCLUSION: Ultrasonic aspiration is effective in obtaining complete removal of
the purulent material and of the dense fibrin layer adherent to the capsule.
However, further studies are warranted to determine its real effectiveness,
compared with the classic technique. In our opinion, it should be considered an
option in more difficult cases, such as abscesses caused by aggressive germs in
young or immunocompromised patients, or in case of recurrent lesions, in order to
avoid craniotomy and open surgery.
PMID- 29948135
TI - Gunshot penetrating brain injury in children: report of three cases with review
of the literature.
AB - INTRODUCTION: Gunshot penetrating brain injury is common in military conflict
area and in urban violence area, but similar incident in pediatric population is
rarely reported. CASE REPORT: We reported three cases of gunshot penetrating
brain injury in children. Two patients had a good recovery after surgery and no
significant deficit on his neurologic function, the other patient was not having
surgery due to the severity of the condition. CONCLUSIONS: We suggest surgery
should be performed immediately to prevent further injury and refractory brain
edema due to the injury, in any case of penetrating brain injury; a good
prognosis can be achieved from early surgery and with appropriate post-operative
treatment.
PMID- 29948136
TI - Short versus mid-long-term outcome of transanal irrigation in children with spina
bifida and anorectal malformations.
AB - PURPOSE: We assessed short- and mid-long-term clinical efficacy of transanal
irrigation (TAI) and its effect on the quality of life of children with spina
bifida (SB) and anorectal malformations (ARM). METHODS: Seventy-four pediatric
patients (age 6-17 years) with SB and ARM with neurogenic bowel dysfunction were
enrolled for a prospective and multicentric study. Patients were evaluated before
the beginning of TAI (T0), after 3 months (T1) and after at least 2 years (range
24-32 months) (T2) using a questionnaire assessing bowel function, the Bristol
scale, and two validated questionnaires on quality of life: the CHQ-PF50
questionnaire for the parents of patients aged 6-11 years and the SF36
questionnaires for patients aged between 12 and 18 years. RESULTS: Seventy-two
patients completed TAI program in T1, and 67 continued into T2. Bowel outcomes
(constipation and fecal incontinence) improved in both the SB and the ARM groups
in the short and mid-long term. In both groups at T1 and T2, parents and children
reported an improvement in quality of life and there was a significant increase
of stool form types 4 and 5 as described by the Bristol scale. Common adverse
effects during the study were similar at T1 and T2 without serious complications.
CONCLUSIONS: We observed a sustained improvement in bowel management and quality
of life in SB and ARM children during the study, more significant in the short
term than in mid-long term. To maintain success rates in the mid-long term and to
reduce the dropout rate, we propose patient training and careful follow-ups.
PMID- 29948137
TI - Neurocutaneous melanosis presenting with hydrocephalus and malignant
transformation: case-based update.
AB - INTRODUCTION: Neurocutaneous melanosis (NCM) is a sporadic condition
characterised by congenital melanocytic nevi and melanocytic thickening of the
leptomeninges. It is believed to result from congenital dysplasia of melanin
producing cells within the skin and leptomeninges. The management of cutaneous
manifestations remains controversial; for neurological manifestations, outcome
remains poor even with the use of radiotherapy and chemotherapy. PATIENTS AND
METHODS: We describe the case of a 5-month-old boy who presented with giant
congenital melanocytic nevus and hydrocephalus. MR imaging and CSF
immunohistochemistry confirmed leptomeningeal melanosis. We discuss the
diagnosis, treatment and prognosis of this rare disorder in the light of recent
published literature. RESULTS: Patient required placement of right-sided
ventriculoperitoneal shunt to control hydrocephalus. The patient tolerated the
procedure well and was discharged home with normal neurological function. A
presumptive diagnosis of NCM was made based on the MR characteristics, CSF
cytology and clinical presentation. He received trametinib, a MAPK/Erk kinase
inhibitor for 7 months. At 30 months of age, he developed left-sided weakness and
status epilepticus requiring paediatric intensive care unit admission and
ventilator support. The patient eventually succumbed to malignant transformation
of leptomeningeal disease. CONCLUSION: Cutaneous manifestations of NCM are
usually congenital, and neurological manifestations develop early in life.
Patients with large or multiple congenital nevi should therefore be investigated
early to facilitate treatment. MR imaging is the investigation of choice which
can further assist in performing biopsy. Symptomatic NCM is refractory to
radiotherapy and chemotherapy and has a poor prognosis. A multidisciplinary
approach is necessary in the management of NCM patients.
PMID- 29948138
TI - Reply to "Childhood Peripheral Facial Palsy".
PMID- 29948139
TI - Spontaneous bone formation in a large craniectomy defect.
PMID- 29948140
TI - Guillain-Barre syndrome in children: subtypes and outcome.
AB - OBJECTIVE: This study reviews the clinical features, subtypes, and outcomes of
childhood Guillain-Barre syndrome (GBS). METHODS: Fifty-four children who
attended a tertiary care training and research hospital in Turkey were enrolled
in the study. RESULTS: The mean age was 6.5 +/- 4.2 years and 32 patients (59.5%)
were male. The most common subtype of GBS was acute inflammatory demyelinating
polyneuropathy (AIDP), which was seen in 27 patients (50%). Having antecedent
history, especially upper respiratory tract infection was significantly more
common in AIDP (P = 0.028). Sensorial symptoms were significantly more frequent
in axonal type GBS (P = 0.001). When we compare the demyelinating and axonal
forms, all of the groups had favorable outcome. CONCLUSION: The diagnosis of
pediatric GBS can be delayed because of its variable presentation. Early
admission to hospital and early treatment are important for decreasing the need
for respiratory support and improving the outcome.
PMID- 29948141
TI - Detecting demineralization of enamel and cementum after gamma irradiation using
radiographic densitometry.
AB - The purpose of this study was to evaluate the ability of radiographic
densitometry in detecting the early demineralization of human enamel and cementum
in irradiated and non-irradiated teeth. Sixty extracted teeth were divided into
two groups: irradiated group and non-irradiated group. After irradiation, the
groups were subjected to demineralization-remineralization (PH) cycling.
Radiographic densitometric measurements (gray values) of a selected area of
interest in the enamel and in the cementum of each tooth were performed at
baseline and after PH cycling. After PH cycling, there was a significant
reduction in gray values for both groups. The difference between "baseline" and
"after PH cycling" values represents the reduction in the mineral content of the
hard tissue, i.e., the demineralization. Results show that the demineralization
of irradiated tooth enamel and cementum was significantly higher compared to that
of non-irradiated tissues as determined by gray-level values. It is concluded
that densitometric measurements by means of digital radiographs allow for the
detection of demineralization of enamel and cementum, and can be used
successfully for diagnosis of the early carious lesions in patients who received
head and neck radiotherapy. This will allow implementation of remineralizing
therapy and avoid the risk of progression of radiation caries. Furthermore, it is
concluded that gamma irradiation with typical therapeutic doses for head and neck
carcinoma is a direct cause of demineralization of tooth enamel and cementum.
PMID- 29948143
TI - The effects of feedback on stability and maneuverability of a phase-reduced model
for cockroach locomotion.
AB - In previous work, we built a neuromechanical model for insect locomotion in the
horizontal plane, containing a central pattern generator, motoneurons, muscles
actuating jointed legs, and rudimentary proprioceptive feedback. This was
subsequently simplified to a set of 24 phase oscillators describing motoneuronal
activation of agonist-antagonist muscle pairs, which facilitates analyses and
enables simulations over multi-dimensional parameter spaces. Here we use the
phase-reduced model to study dynamics and stability over the typical speed range
of the cockroach Blaberus discoidalis, the effects of feedback on response to
perturbations, strategies for turning, and a trade-off between stability and
maneuverability. We also compare model behavior with experiments on lateral
perturbations, changes in body mass and moment of inertia, and climbing dynamics,
and we present a simple control strategy for steering using exteroceptive
feedback.
PMID- 29948142
TI - A streamlined cohesin apparatus is sufficient for mitosis and meiosis in the
protist Tetrahymena.
AB - In order to understand its diverse functions, we have studied cohesin in the
evolutionarily distant ciliate model organism Tetrahymena thermophila. In this
binucleate cell, the heritable germline genome is maintained separately from the
transcriptionally active somatic genome. In a previous study, we showed that a
minimal cohesin complex in Tetrahymena consisted of homologs of Smc1, Smc3, and
Rec8, which are present only in the germline nucleus, where they are needed for
normal chromosome segregation as well as meiotic DNA repair. In this study, we
confirm that a putative homolog of Scc3 is a member of this complex. In the
absence of Scc3, Smc1 and Rec8 fail to localize to germline nuclei, Rec8 is hypo
phosphorylated, and cells show phenotypes similar to depletion of Smc1 and Rec8.
We also identify a homolog of Scc2, which in other organisms is part of a
heterodimeric complex (Scc2/Scc4) that helps load cohesin onto chromatin. In
Tetrahymena, Scc2 interacts with Rec8 and Scc3, and its absence causes defects in
mitotic and meiotic divisions. Scc2 is not required for chromosomal association
of cohesin, but Rec8 is hypo-phosphorylated in its absence. Moreover, we did not
identify a homolog of the cohesin loader Scc4, and no evidence was found of
auxiliary factors, such as Eco1, Pds5, or WAPL. We propose that in Tetrahymena, a
single, minimal cohesin complex performs all necessary functions for germline
mitosis and meiosis, but is dispensable for transcription regulation and
chromatin organization of the somatic genome.
PMID- 29948144
TI - Management of traumatic bile duct injuries in children.
AB - PURPOSE: Pediatric experience with biliary tract injuries (BTI) is limited and
mostly consists of case presentations. The purpose of this study is to evaluate
clinical and radiological findings of possible BTI, treatment strategies, and
results. METHODS: The records of nine patients with the diagnosis of BTI between
July 2009 and November 2017 were reviewed retrospectively. RESULTS: There were
seven boys and two girls (mean 8.05 +/- 4.39 years). The mechanisms were motor
vehicle occupant, fall, crush and gunshot wound. Hepatic laceration routes that
extended into the porta hepatis and contracted the gall bladder were demonstrated
on computerized tomography (CT). Bile duct injury was diagnosed with bile leakage
from the thoracic tube (n = 2), from the abdominal drain (n = 2) and by
paracentesis (n = 5). Extrahepatic (n = 8) and intrahepatic (n = 1) bile duct
injuries were diagnosed by cholangiography. Endoscopic retrograde
cholangiography, sphincterotomy, and stent placement were successfully completed
in five patients. Peritoneal drainage stopped after 3-17 days of procedure in
four patients. The fifth patient was operated with the diagnosis of cystic duct
avulsion. Cholecystectomies, primary repair of laceration, cystic duct ligation,
and Roux-en-Y hepatoportoenterostomy were performed in the remaining four
patients. All patients presented with clinically normal findings, normal liver
functions, and normal ultrasonographic findings in the follow-up period.
CONCLUSIONS: The presentation of the parenchymal injury extending to the porta
hepatis with contracted gall bladder on CT and diffuse homogenous abdominal fluid
should be considered as signs of BTI. We suggest a multi-disciplinary approach
for the diagnosis and treatment of BTIs. Surgery may be indicated according to
the patient's clinical condition, radiological findings and failure of non
operative treatment.
PMID- 29948145
TI - Molecular classification and subtype-specific characterization of skin cutaneous
melanoma by aggregating multiple genomic platform data.
AB - PURPOSE: Traditional classification of melanoma is widely utilized with little
apparent results making the development of robust classifiers that can guide
therapies an urgency. Successful seminal research on classification has provided
a wider understanding of cancer from multiple molecular profiles, respectively.
However, it may ignore the complementary nature of the information provided by
different types of data, which motivated us to subtype melanoma by aggregating
multiple genomic platform data. METHODS: Aggregating three omics data of 328
melanoma samples, melanoma subtyping was performed by three clustering methods.
Differences across subtypes were extracted by functional enrichment,
epigenetically silencing, gene mutations and clinical features. Subtypes were
further distinguished by putative biomarkers. RESULTS: Functional enrichment of
the subtype-specific differential expression genes endowed subtypes new
designation: immune, melanin and ion, in which the first subtype was enriched for
immune system, the second was characterized by melanin and pigmentation, and the
third was enriched for ion-involved transmission process. Subtypes also differed
in age, Breslow thickness, tumor site, mutation frequency of BRAF, PTGS2, CDKN2A,
CDKN2B and incidence of epigenetically silencing for IL15RA, EPSTI1, LXN, CDKN1B
genes. CONCLUSIONS: Skin cutaneous melanoma can be robustly divided into three
subtypes by SNFCC+. Compared with the TCGA classification derived from gene
expression, the subtypes we presented share concordance, but new traits are
excavated. Such a genomic classification offers insights to further personalize
therapeutic decision-making and melanoma management.
PMID- 29948148
TI - [Slowly progressive upper eyelid swelling and ptosis].
PMID- 29948146
TI - Cancer-associated fibroblasts promote gastric tumorigenesis through EphA2
activation in a ligand-independent manner.
AB - PURPOSE: Under physiologic conditions, the binding of erythropoietin-producing
hepatocellular (Eph) A2 receptor and its ligand ephrinA1 results in decreased
EphA2 level and tumor suppression. However, EphA2 and ephrinA1 are highly
expressed in human cancers including gastric adenocarcinoma. In this study, we
tested our hypothesis that cancer-associated fibroblasts (CAFs) promote gastric
tumorigenesis through EphA2 signaling in a ligand-independent manner. METHODS:
Expression of EphA2 protein in primary tumor tissues of 91 patients who underwent
curative surgery for gastric adenocarcinoma was evaluated by immunohistochemistry
and western blotting. Conditioned medium of cancer-associated fibroblasts (CAF
CM) was used to evaluate the tumorigenic effect of CAFs on gastric cancer cell
lines. Epithelial-mesenchymal transition (EMT), cell proliferation, migration,
and invasion were assessed. EphrinA1-Fc ligand was used to determine the
suppressor role of EphA2 receptor-ligand binding. RESULTS: CAF-CM-induced EMT and
promoted cancer cell motility even without cell-cell interaction. Treatment with
a selective EphA2 inhibitor (ALW-II-41-27) or EphA2-targeted siRNA markedly
reduced CAF-CM-induced gastric tumorigenesis. EphrinA1-Fc ligand treatment
showing ligand-dependent tumor suppression diminished the EphA2 expression and
EMT progression. In contrast, ephrinA1-targeted siRNA did not significantly
affect CAF-CM-mediated increases in EphA2 expression and EMT progression.
Treatment with VEGF showed effects like CAF-CM in terms of EphA2 activation and
EMT progression. CONCLUSION: CAFs may contribute to gastric tumorigenesis by
activating EphA2 signaling pathway in a ligand-independent manner. Our results
suggest that ligand-independent activation of EphA2 was triggered by VEGF
released from CAF-CM. Our result may partially explain why ligand-dependent tumor
suppressor roles of EphA2 are not evident in gastric cancer despite the prominent
level of ephrinA1.
PMID- 29948147
TI - Association between pathologic factors and ERG expression in prostate cancer:
finding pivotal networking.
AB - PURPOSE: To evaluate associations between pathologic factors and erythroblast
transformation-specific (ETS)-related gene (ERG) expression in prostate cancer
patients. Using next-generation sequencing, we identified target genes and
regulatory networks. METHODS: ERG expression in 60 radical prostatectomies was
compared with pathological findings by association rule mining with the Apriori
algorithm. Whole-exome and RNA sequencing were performed on three formalin-fixed,
paraffin-embedded ERG-positive and negative prostate cancer samples. A network
diagram identifying dominant altered genes was constructed using Cytoscape open
source bioinformatics platform and GeneMania plugin. RESULTS: Pathologic
conditions positive for perineural invasion, apical margins, and Gleason score 3
+ 4 = 7 were significantly more likely to be ERG-positive than other pathologic
conditions (p = 0.0008), suggesting an association between ERG positivity,
perineural invasion, apical margins, and Gleason score 3 + 4 = 7 (Firth's
logistic regression: OR 42.565, 95% CI 1.670-1084.847, p = 0.0232). Results of
whole-exome and RNA sequencing identified 97 somatic mutations containing common
mutated genes. Regulatory network analysis identified NOTCH1, MEF2C, STAT3, LCK,
CACNA2D3, PCSK7, MEF2A, PDZD2, TAB1, and ASGR1 as pivotal genes. NOTCH1 appears
to function as a hub, because it had the highest node degree and betweenness.
NOTCH1 staining was found 8 of 60 specimens (13%), with a significant association
between ERG and NOTCH1 positivity (p = 0.001). CONCLUSIONS: Evaluating the
association between ERG expression and pathologic factors, and identifying the
regulatory network and pivotal hub may help to understand the clinical
significance of ERG-positive prostate cancer.
PMID- 29948149
TI - [Steroid implant in treatment of sympathetic ophthalmia : Intravitreal implant of
dexamethasone in cystoid macular edema in the context of sympathetic ophthalmia].
AB - We present the case of a 39-year-old female patient with cystoid macular edema of
the left eye in the context of sympathetic ophthalmia. The right eye underwent
several surgical interventions of both cornea and retina after ocular trauma and
was enucleated after first clinical signs compatible with sympathetic ophthalmia
and after exclusion of other infectious/non-infectious etiologies. The patient
was treated with parabulbar triamcinolone injections and intravitreal injections
of a dexamethasone slow-release implant with a good clinical course with respect
to the macular edema. A steroid response did not occur over the treatment period
of more than 12 months.
PMID- 29948150
TI - [Diacaustic examination of the iridocorneal angle : Video article].
AB - BACKGROUND: Several methods are available for the examination of the iridocorneal
angle: gonioscopy and imaging techniques, such as ultrasound biomicroscopy,
optical coherence tomography and Scheimpflug photography play an important role
in the diagnostics of glaucoma. There is, however, a need for simple, easily
applicable methods for screening of the narrow iridocorneal angle in routine
ophthalmological practice. PURPOSE: To apply the diacaustic phenomenon in the
examination of the iridocorneal angle, to describe the method and give its basic
principles. MATERIAL AND METHODS: This article provides a review of the
literature and clinical observations with photographic and video documentation.
The technique is demonstrated in detail with the help of a video and which is
available online. RESULTS: The formation and movement of the diacaustic
phenomenon in the anterior chamber are observed and documented by photography or
video when a light source is moved laterally from front to back. The movement of
the diacaustic line on the anterior surface of the iris and the structures of the
iridocorneal angle are analyzed in relation to other optical phenomena, such as
the Purkinje images 1 and 2, iris shadowing by tangential illumination at the
level of the frill and the limbal crescent of light. The diacaustic test can be
used to determine the depth of the anterior chamber and the width of the
iridocorneal angle. The problems are briefly represented from the perspective of
anatomical, physical and medical history aspects and 4 variants of the diacaustic
line and 3 phases of the movement of the diacaustic light spot are described.
CONCLUSION: The diacaustic test is simple, quick and non-contact. It has
potential as a screening examination of the narrow iridocorneal angle before
medicinal pupil dilation. It can be integrated into the diagnostics of glaucoma
for the assessment of the iridocorneal angle.
PMID- 29948151
TI - [Technique of Descemet membrane endothelial keratoplasty (DMEK) : Video article].
AB - BACKGROUND: Descemet membrane endothelial keratoplasty (DMEK) selectively removes
diseased corneal endothelium and Descemet membrane and replaces them with healthy
donor tissue. The DMEK technique represents the current gold standard for the
treatment of corneal endothelial dysfunction. METHODS: In this article the
surgical technique for DMEK is presented by means of a video. The indications for
surgery, patient education, anesthesia and patient positioning, postoperative
treatment as well as possible complications and their management are described.
RESULTS: The DMEK can be applied for the treatment of a wide range of corneal
endothelial disorders. In addition to the operative implementation, the basis for
the outstanding results of the surgical procedure are careful donor-patient
allocation, thorough examination and follow-up of all patients and experience of
the surgeon. CONCLUSION: The use of DMEK is a safe and effective procedure for
the treatment of corneal endothelial dysfunction. A standardized and
individualized procedure provides the basis for optimal results compared to all
previous transplantation procedures.
PMID- 29948152
TI - [Analysis of real-life data on treatment quality in patients with exudative age
related macular degeneration (AMD) and vein occlusion at a German university eye
hospital].
AB - PURPOSE: Real-life data provide an insight into the reality of patient care under
everyday conditions. Digitization in ophthalmology has led to a structured
documentation of patient data. This makes it possible to automate the retrieval
of a huge amount of real-life data by developing suitable query algorithms.
METHODS: Using an automated query from fully electronic patient documentation,
real-life therapy data were obtained in patients with intravitreal operative drug
delivery (IVOM) in age-related macular degeneration (AMD) and vein occlusion
(VO). Among other things, injection frequency, frequency of visits and best
corrected visual acuity over a total of 4 years of treatment were recorded. The
influence of factors, such as patient age, distance to the clinic and type of
insurance on the quality of care were also investigated. Treatment-naive and
pretreated patients were analyzed. RESULTS: In the first year AMD patients
received an average of 4.59 +/- 2.00 injections with 10.29 +/- 4.47 visits, in
the second year 3.83 +/- 2.23 injections with 7.72 +/- 5.78 visits, in the third
year 3.40 +/- 2.18 injections with 7.19 +/- 5.44 visits and in the fourth year
3.11 +/- 2.29 injections with 6.46 +/- 6.20 visits. The VO patients received an
average of 4.17 +/- 2.15 injections with 9.60 +/- 4.88 visits in the first year,
3.31 +/- 2.03 injections with 7.75 +/- 4.88 visits in the second year, 2.94 +/-
2.00 injections with 6.55 +/- 4.77 visits in the third year and 3.03 +/- 1.94
injections with 7.18 +/- 5.26 visits in the fourth year. The course of the visual
acuity was relatively stable over 4 years. With repect to the quality of care, a
younger patient age and a closer distance to the clinic seemed to have a positive
influence. CONCLUSION: The study results show a positive trend towards an
improved quality of care in intravitreal injection therapy in patients with AMD
and VO. The age of the patient and the place of residence are factors influencing
the therapy.
PMID- 29948153
TI - [Journal Club].
PMID- 29948154
TI - Pediatric low-grade gliomas can be molecularly stratified for risk.
AB - Pediatric low-grade gliomas (PLGGs) consist of a number of entities with
overlapping histological features. PLGGs have much better prognosis than the
adult counterparts, but a significant proportion of PLGGs suffers from tumor
progression and recurrence. It has been shown that pediatric and adult low-grade
gliomas are molecularly distinct. Yet the clinical significance of some of newer
biomarkers discovered by genomic studies has not been fully investigated. In this
study, we evaluated in a large cohort of 289 PLGGs a list of biomarkers and
examined their clinical relevance. TERT promoter (TERTp), H3F3A and BRAF V600E
mutations were detected by direct sequencing. ATRX nuclear loss was examined by
immunohistochemistry. CDKN2A deletion, KIAA1549-BRAF fusion, and MYB
amplification were determined by fluorescence in situ hybridization (FISH).
TERTp, H3F3A, and BRAF V600E mutations were identified in 2.5, 6.4, and 7.4% of
PLGGs, respectively. ATRX loss was found in 4.9% of PLGGs. CDKN2A deletion,
KIAA1549-BRAF fusion and MYB amplification were detected in 8.8, 32.0 and 10.6%
of PLGGs, respectively. Survival analysis revealed that TERTp mutation, H3F3A
mutation, and ATRX loss were significantly associated with poor PFS (p < 0.0001,
p < 0.0001, and p = 0.0002) and OS (p < 0.0001, p < 0.0001, and p < 0.0001). BRAF
V600E was associated with shorter PFS (p = 0.011) and OS (p = 0.032) in a subset
of PLGGs. KIAA1549-BRAF fusion was a good prognostic marker for longer PFS (p =
0.0017) and OS (p = 0.0029). MYB amplification was also a favorable marker for a
longer PFS (p = 0.040). Importantly, we showed that these molecular biomarkers
can be used to stratify PLGGs into low- (KIAA1549-BRAF fusion or MYB
amplification), intermediate-I (BRAF V600E and/or CDKN2A deletion), intermediate
II (no biomarker), and high-risk (TERTp or H3F3A mutation or ATRX loss) groups
with distinct PFS (p < 0.0001) and OS (p < 0.0001). This scheme should aid in
clinical decision-making.
PMID- 29948155
TI - The mechanical leg response to vibration stimuli in cave crickets and
implications for vibrosensory organ functions.
AB - We investigate the influence of leg mechanics on the vibration input and function
of vibrosensitive organs in the legs of the cave cricket Troglophilus neglectus,
using laser Doppler vibrometry. By varying leg attachment, leg flexion, and body
posture, we identify important influences on the amplitude and frequency
parameters of transmitted vibrations. The legs respond best to relatively high
frequency vibration (200-2000 Hz), but in strong dependence on the leg position;
the response peak shifts progressively over 500-1400 Hz towards higher
frequencies following leg flexion. The response is amplified most strongly on the
tibia, where specialised vibrosensory organs occur, and the response amplitude
increases with the increasing frequency. Leg responses peaking at 800 and 1400 Hz
closely resemble the tuning of the intermediate organ receptors in the proximal
tibia of T. neglectus, which may be highly sensitive to positional change. The
legs of free-standing animals with the abdomen touching the vibrating substrate
show a secondary response peak below 150 Hz, induced by body vibration. Such
responses may significantly increase the sensitivity of low-frequency receptors
in the tibial accessory organ and the femoral chordotonal organ. The cave cricket
legs appear suitable especially for detection of high-frequency vibration.
PMID- 29948156
TI - Electric cauterization of the hernia sac in laparoscopic ventral hernia repair
reduces the incidence of postoperative seroma: a propensity score-matched
analysis.
AB - BACKGROUND: Laparoscopic intraperitoneal mesh repair has become one of the most
commonly performed minimally invasive procedures. Nevertheless, despite improved
overall outcome, postoperative seroma formation remains the most frequent
complication. Our objective was to investigate the effectiveness of cauterization
of the hernia sac in terms of reducing the incidence of postoperative seroma
formation. METHODS: A retrospective analysis of 94 patients who underwent
standard laparoscopic intraperitoneal mesh repair without closure of the central
defect (sIPOM) between June 2011 and December 2014 was conducted. In 20 of those
cases, electric cauterization of the hernia sac was additionally performed
(csIPOM). One-to-one propensity score analysis was conducted to overcome patient
selection bias between the two surgical techniques. The case-control group was
matched by gender, body mass index (BMI), patient comorbidities, and surface of
the hernia defect. Patient demographics, pre- and postoperative pain score (using
a ten-point Likert scale), operative data, and complications were collected. At
follow-up, postoperative seroma, hernia recurrence, and chronic pain were
evaluated. RESULTS: Patient demographics, hernia size, comorbidities, and BMI
were similar between the two groups. The csIPOM patient group had significantly
lower rate of seroma formation, compared to the sIPOM control [csIPOM vs. sIPOM 0
vs. 25% (n = 5), p < 0.05]. There was no difference noted regarding postoperative
pain between the two techniques. Hernia recurrence rate was found to be higher in
the sIPOM group [csIPOM vs. sIPOM 0 vs 12.5% (n = 2), p < 0.05]. CONCLUSION: The
present study confirms our hypothesis that laparoscopic sIPOM combined with
electric cauterization of the hernia sac (csIPOM) significantly reduces the rate
of postoperative seroma compared to the sIPOM technique in patients with ventral
and incisional hernias. Further randomized trials are required to verify our
findings.
PMID- 29948157
TI - Seasonal variation in energy expenditure in a rodent inhabiting a winter-rainfall
desert.
AB - Animals that spend more energy than they obtain risk entering allostatic
overload, reducing survival and fitness. They are predicted to adjust their daily
energy expenditure (DEE) during periods of food scarcity. Adjustments of DEE to
changes in food availability have been well-studied in species in temperate zones
during winter, but less so in species enduring seasonal droughts. Likely
mechanisms regulating DEE involve adjustments of activity and maintenance
metabolism. Species that experience seasonal droughts and changes in food
availability, like the African striped mouse (Rhabdomys pumilio), are appropriate
model organisms to study the regulation of seasonal changes of DEE. We quantified
DEE using the 'doubly labelled water' method, measured resting metabolic rate
(RMR), and concomitantly determined activity levels using all-day focal
observations of 69 free-living striped mice in the cold moist season with high
food availability and the hot dry season with low food availability. Striped mice
decreased their DEE in the food scarce dry season using multiple mechanisms,
especially reductions in RMR, and reduced overall physical activity. This was
further facilitated passively by reduced thermoregulatory costs. Our study
demonstrates that animals reduce DEE via active and passive mechanisms in food
restricted environments, and highlights that several environmental factors should
be considered simultaneously when aiming to understand how animals cope with
harsh environments.
PMID- 29948158
TI - Protective effects of compatible solute ectoine against ethanol-induced toxic
alterations in Daphnia magna.
AB - Ectoine (ECT) is a compatible solute synthesized mostly by halophilic
microorganisms subjected to various stressful factors. Its protective properties
in bacteria and some populations of isolated cells subjected to different
stressors are reported; however, little is known on its effects against a
commonly used compound, ethanol (ETH). The purpose of our study was to determine
the effects of ETH alone (at 20 and 60 g/L) and in the combination with various
concentrations of ECT (5, 10, and 25 mg/L) at various times of exposure on
behavioural, physiological, and biochemical parameters of a model invertebrate
Daphnia magna. In the present study, we determined the following parameters:
immobilisation, heart rate, thoracic limb movement, catalase (CAT) activity, and
nitric oxide species (NOx) level. Our study revealed that both concentrations of
ETH alone induced immobilisation and decrease of swimming velocity, heart rate,
and thoracic limb activity; however, catalase activity and NOx levels were
increased. On the other hand, the animals exposed to the combinations of ETH +
ECT showed a reduced immobilisation and alleviated inhibition of heart rate and
thoracic limb activity, lower increase of CAT activity, and NOx level when
compared to the crustaceans subjected to ETH alone. The most distinct alleviation
of toxic effects was noted in the combinations in which the highest concentration
of ECT were used. The results suggest that ETH may induce oxidative stress in
daphnids and attenuating effects of ECT probably result from its antioxidative
properties.
PMID- 29948159
TI - Thyroid hormone manipulation influences development of cardiovascular regulation
in embryonic Pekin duck, Anas platyrhynchos domestica.
AB - Thyroid hormones are key regulators of avian metabolism and may play a
significant role in development at hatching. To better understand the role of
thyroid hormones in avian development, we examined autonomic control of heart
rate and blood pressure while manipulating thyroid hormone levels in the late
stage embryonic Pekin duck (Anas platyrhynchos domestica). Thyroid hormone levels
were manipulated on day 24 of a 28-day incubation period with the thyroperoxidase
inhibitor methimazole (MMI), triiodothyronine (T3), or saline. On day 25 of
incubation, autonomic tone on cardiovascular function was studied by injections
of cholinergic and adrenergic receptor antagonists. Embryos from all treatment
groups expressed a cholinergic and beta-adrenergic tone on heart rate at this
age. Cholinergic blockade with atropine produced a larger change in heart rate in
the hyperthyroid animals compared with euthyroid animals. In response to beta
adrenergic blockade, hyperthyroid conditions produced a larger decrease in heart
rate compared with euthyroid animals, with no change in mean arterial blood
pressure. In response to alpha-adrenergic blockade, mean arterial blood pressure
decreased in the euthyroid animals and more developed hyperthyroid animals.
Collectively, the data indicate that elevated levels of T3 can influence
maturation of cholinergic and adrenergic receptor-mediated cardiovascular
regulation in developing Pekin ducks near the end of incubation.
PMID- 29948160
TI - Effects of ocean acidification and salinity variations on the physiology of
osmoregulating and osmoconforming crustaceans.
AB - Survival, osmoregulatory pattern, oxygen consumption, energy spent on metabolism,
ammonia excretion, type of oxidized energy substrate, and hepatosomatic index
were evaluated in decapods (an osmoregulating crab, Callinectes danae, and an
osmoconforming seabob shrimp, Xiphopenaeus kroyeri) exposed to carbon dioxide
induced water acidification (pH 7.3, control pH 8.0) and different salinities
(20, 25, 30, 35, and 400/00) for 3 days. Compared to the animals kept at
controlled pH, exposure to reduced pH resulted in the loss of osmoregulatory
capacity in C. danae at all salinities, except for some hyporegulation at 400/00,
and reduced oxygen consumption and ammonia excretion at 20 and 400/00.
Xiphopenaeus kroyeri remained an osmoconformer in all evaluated conditions,
except for some hyporegulation at 400/00, and when exposed to the reduced pH, it
presented changes in oxygen consumption at all salinities and reductions in
ammonia excretion at 20 and 350/00 compared to the control animals. Both species
use protein as the main energy substrate and decrease the hepatosomatic index
when exposed to reduced pH relative to the control. The observed changes may be
associated with changes in the activity of enzymes related to osmoregulation, the
use of amino acids as osmotic effectors of cell volume control and recovery, and
the Bohr effect, and, because the gills are multifunctional organs related to
osmoregulation, the changes may be related to acid-base control, nitrogen
excretion, and respiration, with a change in one of these functions bringing
about changes in the others.
PMID- 29948161
TI - Physiological protective action of dissolved organic carbon on ion regulation and
nitrogenous waste excretion of zebrafish (Danio rerio) exposed to low pH in ion
poor water.
AB - Dissolved organic carbon (DOC) represents a heterogeneous group of naturally
occurring molecules in aquatic environments, and recent studies have evidenced
that optically dark DOCs can exert some positive effects on ionoregulatory
homeostasis of aquatic organisms in acidic waters. We investigated the effects of
Luther Marsh DOC, a dark allochthonous DOC, on ion regulation and N-waste
excretion of zebrafish acutely exposed to either neutral or low pH in ion-poor
water. In the first experiment, simultaneous exposure to pH 4.0 and DOC greatly
attenuated the stimulation of Na+ diffusive losses (J outNa ), and prevented the
blockade of Na+ uptake (J inNa ) seen in zebrafish exposed to pH 4.0 alone,
resulting in much smaller disturbances in Na+ net losses (J netNa ). DOC also
attenuated the stimulation of net Cl- losses (J netCl ) and ammonia excretion (J
netAmm ) during acidic challenge. In the second experiment, zebrafish acclimated
to DOC displayed similar regulation of J inNa and J outNa , and, therefore,
reduced J netNa at pH 4.0, effects which persisted even when DOC was no longer
present. Protective effects of prior acclimation to DOC on J netCl and J netAmm
at pH 4.0 also occurred, but were less marked than those on Na+ balance. Urea
fluxes were unaffected by the experimental treatments. Overall, these effects
were clearly beneficial to the ionoregulatory homeostasis of zebrafish at low pH,
and were quite similar to those seen in a recent parallel study using darker DOC
from the upper Rio Negro. This suggests that dark allochthonous DOCs share some
chemical properties that render fish tolerant to ionoregulatory disturbances
during acidic challenge.
PMID- 29948162
TI - Estimating age and the probability of being at least 18 years of age using third
molars: a comparison between Black and White individuals living in South Africa.
AB - Third molar development of 705 White and 563 Black South African individuals aged
between 15 and 25 years was assessed from panoramic radiographs obtained from the
School of Dentistry, University of Pretoria, South Africa. The maxillary and
mandibular left third molars were scored according to a ten-stage scoring system.
Ancestry and sex differences in dental maturity were assessed, and the likelihood
of an individual being 18 years of age was determined for each developmental
stage. Statistically significant differences were noted among ancestry groups for
most developmental stages, with South African Black individuals consistently
maturing earlier than the White individuals. Statistically significant
differences were noted among sex groups for some of the stages, mostly those near
the final stages of root development. The results indicate that male third molars
completed their development faster than that of females. The likelihood of an
individual being 18 years of age based on the third molar development stage for
the maxilla and mandible on its own was also determined. Combined likelihood
results, for the maxillary and mandibular left third molars for stage H,
increased the likelihood of being 18 years to 95% for all the studied ancestry
and sex groups.
PMID- 29948164
TI - In focus in HCB.
PMID- 29948163
TI - Mutability analysis towards 21 STR loci included in the AGCU 21 + 1 kit in
Chinese Han population.
AB - To further illustrate the mutation traits of 21 autosomal STR loci involved in
the newly developed AGCU 21 + 1 kit, randomly selected 485 trios were focused on.
We have previously confirmed the biological father-mother-child relationships of
these trios. Then matters of mutation rates, steps, and origins of the 21 STR
loci were statically analyzed. Results showed 35 mutation events occurred at 16
STR loci of the panel during 20,370 meiosis, and the locus-specific mutation
rates ranged from 0.000 to 1.134% (D3S4529), with an overall mutation rate of
1.72 * 10-3 (95%CI, 1.20-2.39 * 10-3). Mutation origins exhibited slight
discrepancy between male and female germlines, 18 of the 35 mutation events were
verified to be contributed by fathers and 13 by mothers, with origins of the
remaining 4 events hardly to be assigned. Furthermore, 77.14% of the mutations
were one-step mutation. Currently, portraits on mutability of the STR loci
involved in the AGCU 21 + 1 panel were barely reported. In view of this, we
conclude our data will enrich the mutation information of the 21 STR loci and
provide valuable suggestions in calculating likelihood ratios for mutation
involved parental testing cases.
PMID- 29948165
TI - Technique of sonographic assessment of lower uterine segment in women with
previous cesarean delivery: a prospective, pre/intraoperative comparative
ultrasound study.
AB - OBJECTIVE: The purpose of this study was: (A) to establish the effects of
different ultrasound measurement methods (linear versus curved array) and
measuring conditions [impact of pressure by fetal head/pelvis on the lower
uterine segment (LUS)] during LUS-muscular-thickness measurement, (B) to
introduce the intraoperative ultrasound measurement of LUS-muscular thickness
(reference measurement method), and (C) to evaluate the correlation between
different combinations of LUS-muscular-thickness measurement ultrasound
techniques at birth planning and preoperative versus intraoperative measurements.
METHODS: A prospective clinical observational study of women with the previous
cesarean delivery was conducted. LUS-muscular thickness was measured: first at
birth planning and second preoperatively using linear and curved probes
(transabdominal) and an endocavitar probe (transvaginal), examined with and
without pressure by fetal head/pelvis on LUS during measurement and third
intraoperatively during repeat cesarean. Bland-Altman plots, paired t tests,
Pearson's correlation coefficient, and scatter plots were used. RESULTS: Thirty
three women were included in the study (ultrasound measurements: n = 601). There
was no systematic difference between LUS-muscular-thickness measurements with
linear versus curved array (mean difference = 0.06 mm; p = 0.24; nm = 133) but
between measurements with pressure by the fetus versus without (mean difference =
- 0.37 mm; p < 0.001; nm = 243). The highest correlation coefficients were
detected for the preoperative (at the day of cesarean section), transabdominal
vaginal approach combined ultrasound measurements versus the intraoperative
ultrasound measurements of LUS-muscular thickness-as long as the measurements
were made without pressure from the fetal head/pelvis on the LUS [0.86, p <
0.001, n = 24, 95% CI (0.70, 0.94)]. CONCLUSIONS: The systematic application of
predetermined measuring conditions, standardized setup criteria improves the
performance of LUS thickness measurement by ultrasound near term. CLINICALTRIALS.
GOV IDENTIFIER: NCT02827604.
PMID- 29948166
TI - Correction to: Promotor analysis of ESR1 in endometrial cancer cell lines,
endometrial and endometriotic tissue.
AB - In the original publication of the article, the name of first author was
misspelled. The correct name has been copied below.
PMID- 29948167
TI - Invasive prenatal diagnosis of alpha-thalassemia to control Hb Bart's hydrops
fetalis syndrome: 15 years of experience.
AB - PURPOSE: The aim of the present study was to report experiences with invasive
prenatal diagnosis of alpha-thalassemia for the prevention of Hb Bart's hydrops
fetalis syndrome in the Guangxi Zhuang Autonomous Region, China. METHODS:
Pregnant women and their partners who tested positive for alpha0-thalassemia or
were diagnosed with HbH diseases were counseled and suggested to undergo a
prenatal diagnostic procedure for alpha-thalassemia. Fetal material was obtained
by chorionic villus sampling (CVS) between 9 and 13 weeks of gestation, by
amniocentesis between 16 and 24 weeks of gestation and by cordocentesis after 24
weeks of gestation. The alpha0-thalassemia gene types were detected by gap
polymerase chain reaction (Gap-PCR). All results were finally confirmed by DNA
analysis after delivery or termination of pregnancy. RESULTS: An invasive
prenatal alpha-thalassemia diagnosis was performed in 3155 cases at risk for Hb
Bart's hydrops fetalis syndrome at our hospital from 2002 to 2016. CVS was
performed in 1559 cases (49.4%), amniocentesis in 1240 cases (39.3%) and
cordocentesis in 356 cases (11.3%). In total, 786 fetuses were diagnosed as Hb
Bart's hydrops fetalis syndrome. Among these cases, the alpha-thalassemia
genotype was --SEA/--SEA in 784 cases and --SEA/--THAI in 2 cases. All affected
pregnancies were terminated in time. CONCLUSIONS: This extensive experience
suggests that carrier screening, molecular diagnostics, genetic counselling, and
prenatal diagnosis are effective measures to prevent Hb Bart's hydrops fetalis
syndrome.
PMID- 29948168
TI - Day 6 blastocyst is associated with increased birth weight in full-term singleton
newborns after frozen-thawed transfer.
AB - PURPOSE: The purpose of the study is to compare the newborns weight in singleton
term birth following transfer of thawed blastocysts-frozen on either day 5 or day
6 after in vitro fertilization. METHOD: The retrospective study included 1444
frozen-thawed blastocyst transfer (FBT) cycles resulting in live singleton births
between Jan 2013 and Dec 2016. The main outcomes measured were absolute birth
weight, z-score adjusted for gestational age and gender, and incidence of large
for-gestational-age (LGA) newborns. Generalized linear model (GLM) and logistic
regression were used in multivariate analyses. RESULT(S): Both the absolute birth
weight (3416.49 +/- 404.74 vs 3349.22 +/- 416.17) and the z-score (0.6 +/- 0.93
vs 0.41 +/- 0.93) were significantly higher on day 6 FBT in comparison with day 5
FBT. The incidence of LGA newborns was also increased on day 6 FBT (22.8 vs
14.7%, P = 0.006). Adjusted for maternal age, BMI, PCOS diagnosis, present of
vanishing twin, and embryo quality, the odds ratio (95% confidence interval) for
LGA on day 6 FBT comparing with day 5 FBT was 1.76 (1.18-2.64). CONCLUSION(S):
Day 6 FBT is associated with increased birth weight and contributes to the
incidence of LGA newborns in FBT.
PMID- 29948169
TI - Study on the cephalopelvic relationship with cephalic presentation in nulliparous
full-term Chinese pregnant women by MRI with three-dimensional reconstruction.
AB - PURPOSE: To analyze the relationship between fetal head size and maternal pelvis
size using magnetic resonance imaging (MRI) with a 3-D reconstruction technique.
METHODS: A total of 301 nulliparous full-term Chinese pregnant women with
cephalic presentation were enrolled and received MRI examinations before labor
onset. Data were collected and imported into Mimics software to reconstruct the
maternal pelvis and fetus. RESULTS: Of 301 pregnant women, 212 underwent vaginal
delivery and 32 received cesarean section. The body mass index (BMI) was
significantly different between the vaginal delivery group and the suspected
cephalopelvic disproportion (CPD) group; the larger the BMI, the higher was the
risk of CPD. The transverse diameter of the pelvic inlet and the posterior
sagittal diameter of the midpelvis were significantly larger in the vaginal
delivery group, compared with the suspected CPD group. Fetal weight > 3.5 kg
could be used as a diagnostic indicator for CPD. CONCLUSIONS: BMI is a risk
factor for CPD, and fetal weight < 3.5 kg is an important diagnostic indicator
for natural delivery in Chinese pregnant women.
PMID- 29948170
TI - Sexual functioning after total versus subtotal laparoscopic hysterectomy.
AB - AIM: To evaluate postoperative sexual functioning and the influence of patients'
expectations on the change in sexuality following laparoscopic total (TLH) versus
subtotal hysterectomy (LASH). METHODS: A total of 120 women undergoing
laparoscopic hysterectomy were preoperatively enrolled in this bicentric
prospective study. Sexual functioning (SF) was evaluated using the female sexual
function index (FSFI). Additionally, participants filled in a standardised
questionnaire concerning expected changes in SF after surgery. At 3, 6 and 12
months following surgery, women were asked again to assess their level of SF
(FSFI). Data of women who participated in at least one FSFI follow-up assessment
were analysed (n = 92). We compared the change in SF after surgery between
patients with TLH (n = 46) and LASH (n = 46). Additionally, we calculated
regression analyses with the patients' expectations as a predictor for change in
FSFI scores. RESULTS: Comparing the change of FSFI scores after surgery in both
collectives revealed differences only 3 months after surgery, as improvement was
stronger for the LASH collective compared to the THL group (p = 0.006). There
were no changes comparing collectives after 6 (p = 0.663) and 12 (p = 0.326)
months. Concerning patients' expectations, for the LASH group baseline SF (p <
0.001), but not expectations (p = 0.567) predicted the strength of change at each
of the follow ups: a lower level of baseline SF was linked to a stronger
improvement after surgery. For the THL collective, both baseline SF (p < 0.001)
as well as patients' expectations (3 months: p = 0.077, 6 months: p = 0.37, 12
months: p = 0.024) predicted the strength of change: both, a lower level of
baseline SF and higher expectations towards an improvement predicted a stronger
improvement. CONCLUSION: The preservation of the cervix does not show an
advantage in improving SF after surgery. Both methods induce a comparable
improvement in long-time SF, especially in patients with an impaired sexuality
pre-surgery. Furthermore, patients' expectations concerning this matter seem to
have an impact on the postoperative outcome; therefore, this circumstance should
be considered in future projects.
PMID- 29948171
TI - The impact of distractions and interruptions during Cesarean Sections: a
prospective study in a London teaching hospital.
AB - PURPOSE: During Cesarean Sections, distractions which interrupt task specific
activities include auditory, equipment, theatre traffic, and irrelevant
communication. Aims of this study were to investigate frequency and types of
distractions and to assess impact on patient safety and theatre efficiency.
METHODS: Prospective observational study in a London hospital in women undergoing
elective and emergency Cesarean Sections. Distractions were recorded
prospectively in primiparous women having uncomplicated elective and emergency
Cesarean Sections over a 4 week period. Level of distraction is categorized as I:
no noticeable impact on surgical team; II: >= 1 team member affected; and III:
all members affected. Safety outcomes assessed included perioperative
complications such as postpartum hemorrhage, organ injury, postsurgical pyrexia
(first 48 h), return to theatre, readmissions, and postdelivery anemia < 7 g/dl.
RESULTS: Data from 33 elective and 23 emergency cases were collected. Mean number
of level II/III distractions/case was 13.20 (+/- 6.93) and number of level II/III
distracting events was greater during elective compared to emergency cases (mean
14.91 vs 12.00, p = 0.04). In total, 17.89% of distractions occurred during
crucial part of surgery between skin incision and delivery of baby, while delays
resulting from level II/III distractions accounted for 11.25% of total operating
time. There were no intra- or postoperative complications observed in the cohort
of cases. CONCLUSIONS: Distractions did not culminate in perioperative
complications, but disrupted surgeons' task activity, prolonging mean procedure
duration by 26.8%. Recognising sources and effects of distractions will enable
measures to be taken to improve theatre productivity and patient safety.
PMID- 29948172
TI - Association between pelvic floor dysfunction, and clinical and ultrasonographic
evaluation in primiparous women: a cross-sectional study.
AB - PURPOSE: Disorders related to pelvic floor include urinary incontinence (UI),
anal incontinence, pelvic organ prolapse, sexual dysfunction and pelvic pain.
Because pelvic floor dysfunctions (PFD) can be diagnosed clinically, imaging
techniques serve as auxiliary tools for establishing an accurate diagnosis. The
objective is to evaluate the PFD in primiparous women after vaginal delivery and
the association between clinical examination and three-dimensional
ultrasonography (3DUS). METHODS: A cross-sectional study was conducted in a in
tertiary maternity. All primiparous women with vaginal deliveries that occurred
between January 2013 and December 2015 were invited. Women who attended the
invitation underwent detailed anamnesis, questionnaire application, physical
examination and endovaginal and endoanal 3DUS. Crude and adjusted predictor
factors for PFD were analyzed. RESULTS: Fifty women were evaluated. Sexual
dysfunction was the most prevalent PFD (64.6%). When associated with clinical
features and PFD, oxytocin use increased by approximately four times the odds of
UI (crude OR 4.182, 95% CI 1.149-15.219). During the multivariate analysis, the
odds of UI were increased in forceps use by approximately 11 times (adjusted OR
11.552, 95% CI 11.155-115.577). When the clinical and obstetrical predictors for
PFD were associated with 3DUS, forceps increased the odds of lesion of the
pubovisceral muscle and anal sphincter diagnosed by 3DUS by sixfold (crude OR
6.000, 95% CI 1.172-30.725), and in multivariate analysis forceps again increased
the odds of injury by approximately 7 times (adjusted OR 7.778, 95% CI 1.380
43.846). CONCLUSION: Sexual dysfunction was the most frequent PFD. The use of
forceps in primiparous women was associated with a greater chance of UI and
pelvic floor muscle damage diagnosed by 3DUS.
PMID- 29948173
TI - Correction to: Single lung transplantation for lymphangioleiomyomatosis: a single
center experience in Japan.
AB - In the original publication, Fig. 3 has been incorrectly published. The correct
version of Fig. 3 is given in this Correction.
PMID- 29948174
TI - Neuropeptide signalling in the central nucleus of the amygdala.
AB - The central amygdala has a rich repertoire of neuropeptides and neuropeptide
receptors. The diverse ways in which they modulate neuronal activity and
influence synaptic activity are discussed here mostly in the context of fear and
anxiety-related behaviour but also with respect to nociception, hunger and
satiety and chronic alcohol exposure that often come together with anxiety. It
appears that neuropeptides exert rather specific effects on behaviour and
physiology that can be quite different from the effects evoked by opto- or
chemogenetical stimulation of the central amygdala neurons that synthesise them
or express their receptors. Also, neuropeptides might work synergistically or
antagonistically to fine-tune the final outcome of sensory processing in the
central amygdala and bring about appropriate physiological and behavioural
responses to threat. Taken together, we propose that neuropeptide signalling in
the central amygdala mainly serves to establish or maintain emotional homeostasis
in response to threatening and other sensory stimuli.
PMID- 29948175
TI - Clinical value of CSF amyloid-beta-42 and tau proteins in Progressive
Supranuclear Palsy.
AB - Progressive Supranuclear Palsy (PSP) is a four-repeat tauopathy with high
phenotypic and neuropathological variability, highlighting the urgent need for
effective disease biomarkers. Quantitative analysis of cerebrospinal fluid (CSF)
proteins reflecting pathological changes of CNS is currently used as biomarkers
of multiple neurodegenerative disorders for both early differential diagnosis and
prognostic clustering of patients. In this study, we thus assessed the clinical
usefulness of a panel of CSF biomarker in PSP patients presenting with
Richardson's Syndrome. CSF levels of 42-beta-amyloid, total-tau, phosphorylated
tau, and both 42-beta-amyloid/phosphorylated-tau and phosphorylated-tau/total-tau
ratios were comparatively evaluated in 39 PSP patients, 31 patients with
Parkinson's Disease (PD) and 58 gender-/age-matched healthy controls. Specific
gold-standard clinical scores were obtained. Diagnostic accuracy and clinical
correlates of each biomarker were measured with receiver operating curve analysis
and Spearman's test/linear regression, respectively. In PSP, 42-beta-amyloid was
lower than either controls or PD; total-tau and phosphorylated-tau were instead
reduced compared to controls, but similar to PD. At the cut-off value of 623
pg/ml, 42-beta-amyloid significantly distinguished PSP from controls and PD.
Likewise, phosphorylated-tau/total-tau ratio also supported differential
diagnosis between PSP and PD (cut-off = 0.185). 42-beta-amyloid was inversely
associated with PSP severity, as measured with PSP Rating Scale. Our study
demonstrates that CSF 42-beta-amyloid is reduced in PSP patients, proportionally
to clinical severity, thus suggesting a potential use as disease biomarker.
Moreover, phosphorylated-tau/total-tau ratio resulted helpful in the early
differential diagnosis between PSP and PD.
PMID- 29948176
TI - Macular peeling-induced retinal damage: clinical and histopathological evaluation
after using different dyes.
AB - PURPOSE: To describe functional and histopathological findings after macular
peeling using different dyes. METHODS: Prospective, randomized, comparative,
interventional, and immunohistochemical study. Forty-five eyes from 45 patients
with idiopathic epiretinal membrane (ERM) underwent pars plana chromovitrectomy
with ERM and inner limiting membrane (ILM) using trypan blue 0.15% + brilliant
blue 0.05% + lutein 2% in group 1 (15 eyes), trypan blue 0.15% + brilliant blue
0.025% + polyethylene glycol 3350 4% in group 2 (15 eyes), and indocyanine green
0.05% in group 3 (15 eyes). We evaluated visual acuity (VA) and macular
sensitivity (MS) preoperatively, 1, 3, and 6 months after surgery. The expression
of glial fibrillary acidic protein (GFAP) and neurofilament protein (NF) was
assessed immunohistochemically on the ILMs peeled as markers of glial and
neuronal cells. RESULTS: In group 1, both mean VA and MS were significantly
better at 1 and 3 months after surgery (P < 0.05), whereas no significant
difference was found after 6 months. GFAP and NF expression was significantly
lower in group 1 (P < 0.05). CONCLUSIONS: The ERM/ILM peeling is thought to rip
off the intraretinal tissue, based on the amounts of GFAP and NF in the
specimens. The use of lutein dyes reduces iatrogenic stress to the retinal tissue
and allows a faster functional recovery in the first 3 months after surgery,
suggesting a less iatrogenic adhesion to the retinal tissue.
PMID- 29948177
TI - Fixation behavior in macular dystrophy assessed by microperimetry.
AB - PURPOSE: To investigate the fixation behavior in macular dystrophy using
microperimetry. METHODS: This retrospective study included patients with macular
dystrophy and unilateral macular pucker. Macular dystrophic eyes were compared
based on fixation within or outside of the atrophic region. The normal fellow
eyes in patients with unilateral macular pucker formed the control group.
Clinical and demographic characteristics of age, sex, best-corrected visual
acuity, spherical equivalent, and fixation behavior (which included foveal mean
sensitivity (MS), fixation MS, MS improvement, stability, centrality, and
eccentric distance of fixation) were analyzed. A total of 58 patients were
recruited, comprising 29 eyes of 29 patients in the macular dystrophy group and
29 eyes of 29 patients in the control group. RESULTS: Compared to the control
group, patients with macular dystrophy had significantly poorer visual acuity,
foveal MS, fixation MS, stability, and centrality, and more eccentric preferred
retinal locations (PRLs). In macular dystrophy, the PRLs were most common on the
superior side (48.3%). Compared to fixation in the atrophic region, PRLs out of
the atrophic lesion gained more MS (7.41 vs. 0.89 dB, p = 0.001), although with
less stable fixation (10.0 vs. 47.4%, p = 0.044). By multivariate linear
regression, eccentric distance was found to be significantly associated with MS
improvement (p = 0.023). CONCLUSIONS: The commonest location of PRLs in macular
dystrophy is anatomically superior to the lesion. The dystrophic eye can gain
better sensitivity by using PRLs outside the atrophic area.
PMID- 29948178
TI - Aqueous cytokine levels associated with severity of type 1 retinopathy of
prematurity and treatment response to ranibizumab.
AB - PURPOSE: To determine the aqueous humor levels of cytokines in eyes with type 1
retinopathy of prematurity (ROP) before primary intravitreal injection of
ranibizumab (IVR). METHODS: Forty-nine infants with type 1 ROP (56 eyes of 28
infants in the threshold ROP group and 42 eyes of 21 infants in the type 1 pre
threshold ROP group) received primary IVR and 49 aqueous humor samples were
obtained preoperatively. Aqueous humor samples from 15 infants (15 eyes)
undergoing congenital cataract surgery were used as controls. The concentrations
of 27 cytokines were measured by a multiplex bead assay. Infants with persistent,
recurrent, or progressive ROP after IVR were retreated. RESULTS: The preoperative
aqueous levels of 16 cytokines were significantly different among type 1 pre
threshold, threshold ROP, and control groups (P < 0.05). The concentrations of
vascular endothelial growth factor (VEGF) (P < 0.001), interferon-gamma (P <
0.001), interleukin (IL)-10 (P < 0.001), and IL-12 (P < 0.001) were the highest
in the threshold ROP group, less in the type 1 pre-threshold ROP group, and the
lowest in the control group. Retreatment was given to 55% of infants with ROP
within a 48-week follow-up period after primary IVR. Higher VEGF (hazard ratio
[HR] = 1.001, P = 0.001) and macrophage inflammatory protein-1beta (HR = 1.085, P
= 0.022) levels were independently correlated with ROP retreatment. CONCLUSIONS:
Higher aqueous levels of VEGF and inflammatory cytokines were associated with
more severe type 1 ROP and ROP retreatment after primary IVR.
PMID- 29948179
TI - Quantification of radiation retinopathy after beam proton irradiation in
centrally located choroidal melanoma.
AB - PURPOSE: To localize and quantify ischemic changes induced by proton beam
irradiation of central choroidal melanoma and to identify baseline predictors
correlated with the extent of ischemic changes. METHODS: Retrospective chart
review of patients with central choroidal melanoma treated by proton beam
irradiation and conducted widefield fluorescein angiography (>= 20 months after
radiation therapy). Quantification and location of ischemic areas and correlation
to baseline predictors. Multiple linear regression model was performed for
analyses. RESULTS: Twenty-five eyes from 25 patients were included in final
analysis. Mean largest basal tumor area was 56.6 +/- 40.0 mm2 and mean maximal
tumor prominence 2.5 +/- 1.4 mm. Mean total radiated area was 339.1 +/- 68.3 mm2.
All patients showed ischemic changes. Mean ischemic area was 387.6 +/- 123.3 mm2
and mean ischemic index (ischemic area/total visible area) was 0.53 +/- 0.23.
Twenty-two patients (88%) presented ischemic changes outside of the irradiation
field, which comprised of 23% of total ischemic area. Mean angular distance
between lateral border of irradiation field and ischemic area outside of the
radiated area was 44.8 +/- 36.5 degrees . Multivariable analysis revealed a
positive correlation of total ischemic area with total radiated area (p = 0.02)
and initial sonographic tumor prominence (p = 0.02). CONCLUSIONS: Ischemic
changes induced by proton beam irradiation of central choroidal melanoma were
localized and quantified. Ischemic changes exceed the tumor area distinctly and
are found also outside of the irradiation field in the majority of patients. Size
of irradiation area and tumor prominence are positively correlated with extent of
ischemic area.
PMID- 29948182
TI - Implicit preference towards slim bodies and weight-stigma modulate the
understanding of observed familiar actions.
AB - Mounting research evidence suggests that motor resonance (MR, i.e., the mapping
of others' actions onto one's own motor repertoire) can be influenced by diverse
factors related to individual differences. However, no evidence has been reported
so far on the effects of physical appearance and negative attitudes toward
obesity to the mechanism of MR. Thirty-six participants (18 normal-weight and 18
overweight) performed a weight discrimination task, in which they were observing
amateur actors reaching and grasping a light or heavy cube with or without
deception (true vs. fake actions). At the end of each video clip, participants
were instructed to indicate the correct cube size (light or heavy). Importantly,
body similarity between observers and actors was manipulated by presenting videos
of normal-weight or overweight actors. Fat phobic attitudes and automatic
preference for normal-weight than obese people were also examined. Signal
detection analysis (d') on the acquired accuracy data has shown that both normal-
and overweight participants were able to better discriminate truthful actions
when performed by the normal-weight as compared to overweight actors.
Furthermore, this finding was negatively correlated with increased scores of fat
phobic attitudes in both groups. Hence, for the first time, we provide
experimental evidence of action simulation being modulated by an implicit visual
sensitivity towards slim bodies.
PMID- 29948180
TI - Peripapillary comet lesions and comet rain in PXE-related retinopathy.
AB - PURPOSE: To study peripapillary comet lesions (PCL) in Italian patients affected
with pseudoxanthoma elasticum (PXE). METHODS: Retrospective review of fundoscopic
and swept-source (SS) optical coherence tomography (OCT) images of patients with
PXE examined at the Regional Reference Center for Hereditary Retinal
Degenerations at the Careggi Teaching Hospital of Florence from 2012 to 2017.
RESULTS: From 148 eyes of 74 patients affected with PXE, we identified 24 eyes of
14 patients (11 were female) with a mean age of 39 years (range, 20-58 years)
characterized by peripapillary comet lesions. Of these 24 eyes, 15 eyes (of 10
patients) were characterized by comet rain. The smallest comet lesion at the OCT
examination appeared as a focal roundish hyper-reflective alteration at the level
of the outer retinal segments and RPE-Bruch's membrane complex; the larger
lesions appeared as circular and ovoid structures with hyper-reflective borders
in the outer nuclear layer. CONCLUSION: The comet lesion formation process
involves the outer layers of the retina and RPE/Bruch's membrane complex. It
consists of a degenerative/rearrangement process of the photoreceptors which
occurs in an area of focal altered RPE/Bruch's membrane resembling the outer
retinal tubulation.
PMID- 29948183
TI - Differences in relative frequency facilitate learning abstract rules.
AB - Humans learn the rules that govern how the elements of their language are
organized over an input that is often not homogeneous (it might contain noise, or
even include rules from different linguistic systems, as it might be the case for
bilinguals). In the present study we explore the conditions under which
participants can learn an abstract rule when it is presented in a heterogeneous
context. Results from six experiments show that listeners can learn a token
independent rule even if it is presented together with some exemplars that
implement a different regularity (Experiment 1a and 1b). In fact, learning rules
from an input containing several patterns does not seem to differ from learning
them from an input containing only one (Experiment 1c). More surprisingly, we
observed that listeners can even learn an abstract rule that is only implemented
over 10% of the exemplars that compose a familiarization stream (Experiments 2a
and 2b). When the proportion of tokens implementing the target and the non-target
rules is balanced, we did not observe any learning (Experiment 3). Our results
suggest that listeners use differences in relative frequency to keep separate
linguistic rules apart. This allows them to learn different abstract regularities
from a non-homogeneous linguistic signal.
PMID- 29948184
TI - Cognitive flexibility and religious disbelief.
AB - Cognitive flexibility is operationalized in the neuropsychological literature as
the ability to shift between modes of thinking and adapt to novel or changing
environments. Religious belief systems consist of strict rules and rituals that
offer adherents certainty, consistency, and stability. Consequently, we
hypothesized that religious adherence and practice of repetitive religious
rituals may be related to the persistence versus flexibility of one's cognition.
The present study investigated the extent to which tendencies towards cognitive
flexibility versus persistence are related to three facets of religious life:
religious affiliation, religious practice, and religious upbringing. In a large
sample (N = 744), we found that religious disbelief was related to cognitive
flexibility across three independent behavioural measures: the Wisconsin Card
Sorting Test, Remote Associates Test, and Alternative Uses Test. Furthermore,
lower frequency of religious service attendance was related to cognitive
flexibility. When analysing participants' religious upbringing in relation to
their current religious affiliation, it was manifest that current affiliation was
more influential than religious upbringing in all the measured facets of
cognitive flexibility. The findings indicate that religious affiliation and
engagement may shape and be shaped by cognitive control styles towards
flexibility versus persistence, highlighting the tight links between flexibility
of thought and religious ideologies.
PMID- 29948185
TI - Olfactory perception and blindness: a systematic review and meta-analysis.
AB - Anecdotal reports suggest that blind people might develop supra-normal olfactory
abilities. However, scientific evidence shows a mixed pattern of findings.
Inconsistent observations are reported for both sensory-driven olfactory tasks
(e.g., odor threshold) and higher-order olfactory functions (e.g., odor
identification). To quantify the evidence systematically, we conducted a review
and meta-analysis. Studies were included if they examined olfactory function
(i.e., odor threshold, odor discrimination, free odor identification, or cued
odor identification) in blind compared with a sighted control group. Articles
were identified through computerized literature search. A total of 18 studies
focused on olfactory threshold (n = 1227: 590 blind and 637 sighted individuals),
14 studies targeted discrimination (n = 940: 455 blind and 485 sighted), 14
studies measured cued identification (n = 968: 468 blind and 500 sighted), and 7
studies (n = 443: 224 blind and 219 sighted individuals) assessed free
identification. Overall, there were no differences in effect sizes between the
blind and sighted individuals after correcting the results for publication bias.
We additionally conducted an exploratory analysis targeting the role played by
three moderators of interests: participants' age, the proportion of women versus
men in each of the studies included into meta-analysis and onset of blindness
(early blind vs. late-blind). However, none of the moderators affected the
observed results. To conclude, blindness seems not to affect cued/free odor
identification, odor discrimination or odor thresholds.
PMID- 29948186
TI - Deep, effortless concentration: re-examining the flow concept and exploring
relations with inattention, absorption, and personality.
AB - Conceptualizing the construct of flow in terms of 'deep and effortless
concentration', we developed two measurement scales designed to index individual
differences in flow during 'internal' tasks, such as thinking (deep effortless
concentration: internal-DECI) and during 'external' tasks, such as while playing
a sport (deep effortless concentration: external-DECE). These scales were highly
correlated, indicating that individuals prone to experiencing flow in external
contexts are also prone to experience flow in internal contexts. Nonetheless, a
measurement model construing internal and external flow as related, but separate,
constructs was found to fit the data significantly better than a model where they
were construed as a single construct. We then explored associations between flow
and various forms of everyday inattention. In addition, we explored the relation
between flow and the Tellegen Absorption Scale (TAS), an index of absorption, as
well as the Big Five personality traits. Amongst other things, we found that flow
was negatively related to inattention, indicating that people who experience flow
more frequently may experience relatively less inattention in everyday contexts.
PMID- 29948187
TI - Person information facilitates memory for face identity.
AB - We tested whether episodic information about people facilitates memory for their
faces (Experiment 1) and whether this effect is specific for face identity
(Experiment 2). Participants were presented with faces paired with behavioral
descriptions (positive, neutral, or negative) and faces displayed alone. In both
experiments, participants were more likely to recognize faces paired with
behavioral descriptions, and after 1-week delay, their memory was better for
faces paired with descriptions of salient behavior (i.e., with positive and
negative valence) than faces paired with neutral behaviors or faces presented
without information. To examine whether these effects are about memory for face
identity rather than face image memory, in Experiment 2, we presented different
facial images (varying in facial angle) of the same people at the encoding and at
the recognition test. Although this manipulation decreased the overall
recognition, the findings of Experiment 1 were fully replicated. The findings
suggest that minimal affective information is sufficient to facilitate memory for
face identity.
PMID- 29948188
TI - Central serotonin modulates neural responses to virtual violent actions in
emotion regulation networks.
AB - Disruptions in the cortico-limbic emotion regulation networks have been linked to
depression, anxiety, impulsivity, and aggression. Altered transmission of the
central nervous serotonin (5-HT) contributes to dysfunctions in the cognitive
control of emotions. To date, studies relating to pharmaco-fMRI challenging of
the 5-HT system have focused on emotion processing for facial expressions. We
investigated effects of a single-dose selective 5-HT reuptake inhibitor
(escitalopram) on emotion regulation during virtual violence. For this purpose,
38 male participants played a violent video game during fMRI scanning. The SSRI
reduced neural responses to violent actions in right-hemispheric inferior frontal
gyrus and medial prefrontal cortex encompassing the anterior cingulate cortex
(ACC), but not to non-violent actions. Within the ACC, the drug effect
differentiated areas with high inhibitory 5-HT1A receptor density (subgenual s25)
from those with a lower density (pregenual p32, p24). This finding links
functional responses during virtual violent actions with 5-HT neurotransmission
in emotion regulation networks, underpinning the ecological validity of the 5-HT
model in aggressive behavior. Available 5-HT receptor density data suggest that
this SSRI effect is only observable when inhibitory and excitatory 5-HT receptors
are balanced. The observed early functional changes may impact patient groups
receiving SSRI treatment.
PMID- 29948189
TI - Evidence for a neural dual-process account for adverse effects of cognitive
control.
AB - Advantageous effects of cognitive control are well-known, but cognitive control
may also have adverse effects, for example when it suppresses the implicit
processing of stimulus-response (S-R) bindings that could benefit task
performance. Yet, the neurophysiological and functional neuroanatomical
structures associated with adverse effects of cognitive control are poorly
understood. We used an extreme group approach to compare individuals who exhibit
adverse effects of cognitive control to individuals who do not by combining event
related potentials (ERPs), source localization, time-frequency analysis and
network analysis methods. While neurophysiological correlates of cognitive
control (i.e. N2, N450, theta power and theta-mediated neuronal network
efficiency) and task-set updating (P3) both reflect control demands and implicit
information processing, differences in the degree of adverse cognitive control
effects are associated with two independent neural mechanisms: Individuals, who
show adverse behavioral effects of cognitive control, show reduced small-world
properties and thus reduced efficiency in theta-modulated networks when they fail
to effectively process implicit information. In contrast to this, individuals who
do not display adverse control effects show enhanced task-set updating mechanism
when effectively processing implicit information, which is reflected by the P3
ERP component and associated with the temporo-parietal junction (TPJ, BA 40) and
medial frontal gyrus (MFG; BA 8). These findings suggest that implicit S-R
contingencies, which benefit response selection without cognitive control, are
always 'picked up', but may fail to be integrated with task representations to
guide response selection. This provides evidence for a neurophysiological and
functional neuroanatomical "dual-process" account of adverse cognitive control
effects.
PMID- 29948190
TI - Early-in-life neuroanatomical and behavioural trajectories in a triple transgenic
model of Alzheimer's disease.
AB - Animal models of Alzheimer's disease (AD) can be used to determine the
progressive neurodegeneration characteristics of AD in vivo using magnetic
resonance imaging (MRI). Given the need for therapeutic interventions before the
onset of frank AD, it is critical to examine if AD models demonstrate
neuroanatomical remodeling in an equivalent preclinical phase. This manuscript
examines the trajectories of brain and behavioural changes in the Triple
transgenic mouse model (3xTg) prior to the development of AD-like behaviours. The
3xTg mimics both beta-amyloid plaques and neurofibrillary tangles through three
mutations associated with familial AD, namely: PS1M146V, APPSwe, and tauP301L
transgenes. We performed detailed investigation using longitudinal structural MRI
at 6, 8, 12, 16, 20, and 24 weeks old to assess neuroanatomical changes using
volumetric and deformation-based analyses. Learning- and memory-related behaviour
were assessed through the Morris water maze at 9, 17, and 25 weeks of age. There
was the absence of major memory deficits with the notable exception of water maze
conducted at 17 weeks old, where 3xTg group spent significantly less time in the
quadrant of interest in the probe trial. Through volumetric and deformation-based
analyses, we observed relative decrease over time in the 3xTg group in the third
ventricle, piriform cortex, fornix, and fimbria relative to the control group. We
also observed decreases over time in the control mice in the hippocampus,
entorhinal cortex, cerebellum, and olfactory bulb. In many of these cases, we
note a delay in the attainment of peak volume in the 3xTgs relative to the
control group, suggesting a possible neurodevelopmental and maturational delay
given the likely over-expression of AD-related pathology from birth. Importantly,
neuroanatomical alterations are observed prior to the manifestation of AD-like
behaviours, suggesting that mutated amyloid and tau are, indeed, sufficient to
cause changes in the neuroanatomy in 3xTg mice, but potentially insufficient to
be responsible for behavioural changes in the earlier stages of life.
PMID- 29948191
TI - Beyond bilingualism: multilingual experience correlates with caudate volume.
AB - The multilingual brain implements mechanisms that serve to select the appropriate
language as a function of the communicative environment. Engaging these
mechanisms on a regular basis appears to have consequences for brain structure
and function. Studies have implicated the caudate nuclei as important nodes in
polyglot language control processes, and have also shown structural differences
in the caudate nuclei in bilingual compared to monolingual populations. However,
the majority of published work has focused on the categorical differences between
monolingual and bilingual individuals, and little is known about whether these
findings extend to multilingual individuals, who have even greater language
control demands. In the present paper, we present an analysis of the volume and
morphology of the caudate nuclei, putamen, pallidum and thalami in 75
multilingual individuals who speak three or more languages. Volumetric analyses
revealed a significant relationship between multilingual experience and right
caudate volume, as well as a marginally significant relationship with left
caudate volume. Vertex-wise analyses revealed a significant enlargement of dorsal
and anterior portions of the left caudate nucleus, known to have connectivity
with executive brain regions, as a function of multilingual expertise. These
results suggest that multilingual expertise might exercise a continuous impact on
brain structure, and that as additional languages beyond a second are acquired,
the additional demands for linguistic and cognitive control result in
modifications to brain structures associated with language management processes.
PMID- 29948192
TI - Electrotonic signal processing in AII amacrine cells: compartmental models and
passive membrane properties for a gap junction-coupled retinal neuron.
AB - Amacrine cells are critical for processing of visual signals, but little is known
about their electrotonic structure and passive membrane properties. AII amacrine
cells are multifunctional interneurons in the mammalian retina and essential for
both rod- and cone-mediated vision. Their dendrites are the site of both input
and output chemical synapses and gap junctions that form electrically coupled
networks. This electrical coupling is a challenge for developing realistic
computer models of single neurons. Here, we combined multiphoton microscopy and
electrophysiological recording from dye-filled AII amacrine cells in rat retinal
slices to develop morphologically accurate compartmental models. Passive cable
properties were estimated by directly fitting the current responses of the models
evoked by voltage pulses to the physiologically recorded responses, obtained
after blocking electrical coupling. The average best-fit parameters (obtained at
60 mV and ~ 25 degrees C) were 0.91 uF cm-2 for specific membrane capacitance,
198 Omega cm for cytoplasmic resistivity, and 30 kOmega cm2 for specific membrane
resistance. We examined the passive signal transmission between the cell body and
the dendrites by the electrotonic transform and quantified the frequency
dependent voltage attenuation in response to sinusoidal current stimuli. There
was significant frequency-dependent attenuation, most pronounced for signals
generated at the arboreal dendrites and propagating towards the soma and lobular
dendrites. In addition, we explored the consequences of the electrotonic
structure for interpreting currents in somatic, whole-cell voltage-clamp
recordings. The results indicate that AII amacrines cannot be characterized as
electrotonically compact and suggest that their morphology and passive properties
can contribute significantly to signal integration and processing.
PMID- 29948193
TI - Chronotype differences in cortical thickness: grey matter reflects when you go to
bed.
AB - Based on individual circadian cycles and associated cognitive rhythms, humans can
be classified via standardised self-reports as being early (EC), late (LC) and
intermediate (IC) chronotypes. Alterations in neural cortical structure
underlying these chronotype differences have rarely been investigated and are the
scope of this study. 16 healthy male ECs, 16 ICs and 16 LCs were measured with a
3 T MAGNETOM TIM TRIO (Siemens, Erlangen) scanner using a magnetization prepared
rapid gradient echo sequence. Data were analysed by applying voxel-based
morphometry (VBM) and vertex-wise cortical thickness (CTh) analysis. VBM analysis
revealed that ECs showed significantly lower grey matter volumes bilateral in the
lateral occipital cortex and the precuneus as compared to LCs, and in the right
lingual gyrus, occipital fusiform gyrus and the occipital pole as compared to
ICs. CTh findings showed lower grey matter volumes for ECs in the left anterior
insula, precuneus, inferior parietal cortex, and right pars triangularis than for
LCs, and in the right superior parietal gyrus than for ICs. These findings reveal
that chronotype differences are associated with specific neural substrates of
cortical thickness, surface areas, and folding. We conclude that this might be
the basis for chronotype differences in behaviour and brain function.
Furthermore, our results speak for the necessity of considering "chronotype" as a
potentially modulating factor in all kinds of structural brain-imaging
experiments.
PMID- 29948194
TI - Reprogramming Halomonas for industrial production of chemicals.
AB - Halomonas spp. are able to grow under a high salt concentration at alkali pH,
they are able to resist contamination by other microbes. Development of Halomonas
spp. as platform production strains for the next-generation industrial
biotechnology (NGIB) is intensively studied. Among Halomonas spp., Halomonas
bluephagenesis is the best studied one with available engineering tools and
methods to reprogram it for production of various polyhydroxyalkanoates,
proteins, and chemicals. Due to its contamination resistance, H. bluephagenesis
can be grown under open and continuous processes not just in the labs but also in
at least 1000 L fermentor scale. It is expected that NGIB based on Halomonas spp.
be able to engineer for production of increasing number of products in a
competitive manner.
PMID- 29948195
TI - Metabolomics profiling reveals the mechanism of increased pneumocandin B0
production by comparing mutant and parent strains.
AB - Metabolic profiling was used to discover mechanisms of increased pneumocandin B0
production in a high-yield strain by comparing it with its parent strain.
Initially, 79 intracellular metabolites were identified, and the levels of 15
metabolites involved in six pathways were found to be directly correlated with
pneumocandin B0 biosynthesis. Then by combining the analysis of key enzymes,
acetyl-CoA and NADPH were identified as the main factors limiting pneumocandin B0
biosynthesis. Other metabolites, such as pyruvate, alpha-ketoglutaric acid,
lactate, unsaturated fatty acids and previously unreported metabolite gamma
aminobutyric acid were shown to play important roles in pneumocandin B0
biosynthesis and cell growth. Finally, the overall metabolic mechanism hypothesis
was formulated and a rational feeding strategy was implemented that increased the
pneumocandin B0 yield from 1821 to 2768 mg/L. These results provide practical and
theoretical guidance for strain selection, medium optimization, and genetic
engineering for pneumocandin B0 production.
PMID- 29948196
TI - Validity of a customized submaximal treadmill protocol for determining VO2max.
AB - INTRODUCTION: A customized submaximal exercise test for cycle ergometry was
reported as a superior estimate of maximum oxygen uptake (VO2max) in comparison
to the traditional YMCA ergometry test. PURPOSE: Following similar methodology,
we sought to validate a customized submaximal treadmill test (CustomTM) compared
with the widely used Bruce submaximal protocol. METHODS: Participants (29 women
and 21 men; age = 31.37 +/- 11.44 year, BMI = 24.02 +/- 3.03) performed a graded
exercise test (GXT) with a subsequent exhaustive, square-wave bout for the
verification of "true" VO2max. In counterbalanced order, subjects then completed
submaximal protocols. The CustomTM protocol consisted of two 3-min stages
estimated at 35 and 70% of VO2max, where VO2max was estimated with a linear
regression equation utilizing sex, BMI, age, and self-reported physical activity.
RESULTS: VO2 values from the GXT and verification bout were 47.2 +/- 7.7 and 47.0
+/- 7.7 ml kg-1 min-1, respectively (ICC = 0.99, CV = 2.0%, TE = 0.83 ml kg-1 min
1), with the highest value used as "true" VO2max (47.7 +/- 7.7 ml kg-1 min-1).
Neither the Bruce (45.95 +/- 6.97 ml kg-1 min-1) nor the CustomTM (47.3 +/- 9.4
ml kg-1 min-1) protocol differed from "true" VO2max. The CustomTM had a "very
large" measurement agreement with "true" VO2max (ICC = 0.78, CV of 9.1%, TE =
4.07 ml kg-1 min-1). Bruce had a "large" measurement agreement with "true" VO2max
(ICC = 0.62, CV of 10.0%, TE = 4.51 ml kg-1 min-1). CONCLUSION: The CustomTM was
superior to the Bruce protocol, because it included a stage below and above gas
exchange threshold, yielded a better measurement agreement for "true" VO2max, and
was more time efficient.
PMID- 29948197
TI - Correction to: A mathematical model of the effects of resistance exercise-induced
muscle hypertrophy on body composition.
AB - There is a typo in the original equation describing lean mass, and it has also
been pointed out to the authors that the model is not strictly energy balanced.
PMID- 29948198
TI - Vastus lateralis muscle tissue composition and motor unit properties in
chronically endurance-trained vs. sedentary women.
AB - This study examined motor unit (MU) amplitudes (APAMPS) and firing rates during
moderate-intensity contractions and muscle cross-sectional area (mCSA) and echo
intensity (mEI) of the vastus lateralis (VL) in chronically endurance-trained and
sedentary females. Eight endurance-trained (ET) and nine sedentary controls (SED)
volunteered for this study. Surface electromyographic (EMG) signals from a five
pin electrode array were recorded from the VL during isometric trapezoid muscle
actions at 40% of maximal voluntary contraction (MVC). Decomposition methods were
applied to the EMG signals to extract the firing events and amplitudes of single
MUs. The mean firing rate (MFR) during steady force and MUAPAMP for each MU was
regressed against recruitment threshold (RT, expressed as %MVC). The y-intercepts
and slopes from the MFR and MUAPAMP vs. RT relationships were calculated. EMG
amplitude during steady force was normalized (N-EMGRMS) to peak EMG amplitude
recorded during the MVC. Ultrasonography was used to measure mCSA and mEI.
Significant differences existed between the ET and SED for the slopes (P = 0.005,
P = 0.001) from the MFR and MUAPAMP vs. RT relationships with no differences for
the y-intercepts (P > 0.05). N-EMGRMS was significantly (P = 0.033) lower for the
ET than SED. There were no differences between groups for mCSA; however, the SED
possessed significantly (P = 0.001) greater mEI. Subsequently, the ET likely
possessed hypertrophied and stronger MUs that allowed for lower necessary muscle
activation to maintain the same relative task as the SED. The larger MUs for the
ET is supported via the MFR vs. RT relationships and ultrasound data.
PMID- 29948199
TI - Clinical and MRI changes of puborectalis and iliococcygeus after a short period
of intensive pelvic floor muscles training with or without instrumentation : A
prospective randomized controlled trial.
AB - PURPOSE: This study evaluates the impact of a 3-week period of intensive pelvic
floor muscles training (PFMT), with or without instrumentation, on clinical and
static magnetic resonance imaging (MRI) changes of puborectalis (PR) and
iliococcygeus (IL) muscles. METHODS: 24 healthy young women were enrolled in the
study and 17 achieved the 9 sessions of 30 min training exercises and conducted
all assessments. Participants were randomly assigned in two training groups:
voluntary contractions combined with hypopressive exercises (HYPO) or biofeedback
exercises combined with transvaginal electrical stimulations (ELEC). Clinical and
T2-weighted MRI assessments were realized before and after training. RESULTS:
Modified Oxford Grading System (MOGS) scores for left PR and perineal body
significantly increased in the two groups (p = 0.039, p = 0.008), but MOGS score
for right PR significantly increased only in HYPO (p = 0.020). Muscle volumes of
right and left IL significantly decreased (p = 0.040, p = 0.045) after training
as well as signal intensities of right and left PR (p = 0.040, p = 0.021) and
thickness of right and left IL at mid-vagina location (p = 0.012, p = 0.011).
CONCLUSIONS: A short period of intensive PFMT induces clinical and morphological
changes in PFMs at rest suggesting a decrease in IL volume and adipose content of
PR. Although the results suggested that an intensive non-instrumented PFMT is as
effective as an instrumented training, future controlled studies with greater
sample sizes are needed to establish the relative and absolute effectiveness of
each of the two interventions.
PMID- 29948200
TI - Echinococcus multilocularis (Cestoda, Cyclophyllidea, Taeniidae): functional
ultrastructure of the penetration glands and nerve cells within the oncosphere.
AB - The fine structure of the infective hexacanths of Echinococcus multilocularis was
examined with particular emphasis on the functional ultrastructure of penetration
glands and nerve cells directly involved in the mechanism of initial host
infection. The oncosphere contains two types of penetration glands, PG1 and PG2,
that differ slightly in size and form a large U-shaped bi-nucleated syncytial
structure. The arms of each gland at each end of the U, directed towards the hook
region, exit into the tegument peripheral layer between the median and lateral
hook pairs. The lobate nuclei of PG1 and PG2 contain prominent spherical nucleoli
surrounded by several large electron-dense islands of heterochromatin. The
syncytial cytoplasm of both types of glands is rich in free ribosomes, polysomes,
several mitochondria, and heavy accumulations of discoid secretory granules of
moderate to high electron density. The secretory granules, sg1 and sg2, differ in
their ultrastructure and electron density; the sg2 are much smaller and more
flattened in shape. A common characteristic for sg1 and sg2, evident under high
magnification, is their high electron density and discoidal shape, with two bi
concave surfaces. Both sg1 and sg2 are frequently grouped in characteristic
parallel stacks, the "rouleau"-shaped assemblages with sometimes six to ten
granules. Two nerve cells of neurosecretory type are situated in the central part
of the hexacanth, each one in a deep U-shaped invagination between the two
penetration glands. The nuclei of nerve cells contain several large
heterochromatin islands closely adjacent to their nuclear membranes. Their
cytoplasm is characterized by having membrane-bound, dense-cored neurosecretory
like granules not only in nerve cell perikarya but also in the elongated nerve
processes frequently adjacent to gland arms and to both somatic or body
musculature, including the complex system of hook muscles. The results of the
present study, when supported with literature data on oncospheres of other
cestode species, allow for a better understanding of the important role and
coordinated functions of three structural components, i.e., oncospheral hooks,
penetration glands, and nerve cells, in the mechanism of intermediate host
infection. Presence or absence of nerve cells in oncospheres of various cestodes
is reviewed, and perspectives on the value and application of research on
functional morphology of oncospheres are discussed.
PMID- 29948201
TI - Isospora sagittulae McQuistion & Capparella, 1992 (Apicomplexa: Eimeriidae) from
antbirds (Passeriformes: Thamnophilidae) in the Amazon and Atlantic Forest of
Brazil: with notes on its distribution and dispersion in the Neotropical region.
AB - In the current study, Isospora sagittulae McQuistion and Capparella, 1992
(Protozoa: Apicomplexa: Eimeriidae) is reported from white-shouldered fire-eyes
Pyriglena leucoptera (Vieillot, 1818) in the Atlantic Forest in southeastern
Brazil. To date, this coccidian species was described from antbirds in Ecuador
and Brazilian Amazon. In this sense, oocysts and measurements of the description
of I. sagittulae from Amazonian antbirds were required from the deposit for
comparison between samples from the Amazon and Atlantic Forest. The morphology
was similar in all aspects, despite the polymorphism associated with the oocyst
shape. DNA sequences for the mitochondrial cytochrome c oxidase subunit 1 (cox1)
locus of the oocysts had similarity of 100%. Therefore, these strong
morphological, molecular, and ecological equivalences ensure the unique
identification of I. sagittulae. Finally, this finding reveals the wide
distribution of I. sagittulae in the Neotropical region and indicates that other
antbirds in the Brazilian Cerrado should disperse I. sagittulae to the Amazon and
Atlantic Forest.
PMID- 29948202
TI - Reproduction of trematodes in the molluscan host: an ultrastructural study of the
germinal mass and brood cavity in daughter rediae of Tristriata anatis
Belopolskaia, 1953 (Digenea: Notocotylidae).
AB - This study describes the fine structure of the germinal mass in daughter rediae
of Tristriata anatis. The germinal mass consists of undifferentiated cells,
germinal cells and supporting cells and contains numerous cercarial embryos up to
tail bud stage. Supporting cells and their outgrowths form a tight meshwork of
the germinal mass. In its basal part, this meshwork serves as scaffolding for
undifferentiated and germinal cells, naked cell aggregates and early germinal
balls. More mature embryos are located apically. The hypertrophied supporting
tissue appears to be involved in an intensive transport of substances, as
indicated by abundant gap junctions between cell outgrowths and numerous
pinocytotic vesicles and microtubules in their cytoplasm. Germinal cells contain
annulate lamellae and the nuage, typical organelles of animal oocytes. In young
rediae containing embryonic cercariae at the tail bud stage, the supporting
tissue starts to degenerate in the apical part of the germinal mass, and a
primordial brood cavity emerges though it develops fully only in mature rediae
containing late embryonic cercariae. An unusual feature of the germinal mass in
T. anatis rediae is an enhancement of the embryo brooding function. At the same
time, the performance of this function by the brood cavity is reduced. This is
the first time such a redistribution of the embryo brooding function between the
germinal mass and the brood cavity has been reported.
PMID- 29948203
TI - The circadian variation of oocyst shedding of Eimeria spp. affecting brown kiwi
(Apteryx mantelli).
AB - Captive rearing of wild brown kiwi (Apteryx mantelli) is widely carried out to
assist in the recovery of this declining species. As a consequence, high
densities of immunologically naive kiwi are commonly housed in semi-captive
conditions, with the potential to result in substantial morbidity and mortality
from coccidiosis caused by multiple species of Eimeria. Previous research has
described circadian variation in oocyst shedding across multiple avian host
species. The aim of this research was to describe any circadian variation in
oocyst shedding in brown kiwi. Droppings were collected from brown kiwi (n = 4)
at a single captive rearing facility using video surveillance to determine the
time of excretion, and oocyst counts were undertaken. Results show that two of
the Eimeria spp. affecting brown kiwi exhibit a peak in oocyst shedding between
03.00 and 07.00 with few or no oocysts shed between 08.00 and midnight. These
results are not able to be explained by the current hypotheses theorising the
evolutionary forces behind the development of this adaptive trait. Our findings
increase the current understanding of the biology of the Eimeria spp. affecting
brown kiwi and have important implications for the management of captive-reared
kiwi, in particular for the accurate interpretation of faecal oocyst counts.
PMID- 29948204
TI - Brain proteomic differences between wild-type and CD44- mice induced by chronic
Toxoplasma gondii infection.
AB - Chronic clinical Toxoplasma gondii (T. gondii) infection is the primary disease
state that causes severe encephalitis. CD44 is a member of the cell adhesion
molecule family and plays an important role in T. gondii infection. However,
proteomic changes in CD44 during chronic T. gondii infection have rarely been
reported. Thus, an iTRAQ-based proteomic study coupled with 2D-LC-MS/MS analysis
was performed to screen CD44-related proteins during chronic T. gondii infection.
As a result, a total of 2612 proteins were reliably identified and quantified.
Subsequently, 259, 106, and 249 differentially expressed proteins (DEPs) were
compared between CD44- mice (A) vs wild-type mice (B), B vs wild-type mice
infected with T. gondii (C), and C vs CD44- mice infected with T. gondii (D).
Gene ontology, KEGG pathway, and protein-protein interaction analyses were
performed on the DEPs. According to the results, immune-related proteins were
altered significantly among the A vs B, B vs C, and C vs D comparisons, which
might indicate that chronic T. gondii infection caused changes in the host
immune response. Additionally, Ca2+- and metabolism-related proteins were
upregulated in C vs D, which supported the hypothesis that CD44 mediated the
production of host Ca2+ and IFN-gamma and that the parasite preferentially
invaded cells expressing high levels of CD44. The present findings validate and
enable a more comprehensive knowledge of the role of CD44 in hosts chronically
infected with T. gondii, thus providing new ideas for future studies on the
specific functions of CD44 in latent toxoplasmosis.
PMID- 29948205
TI - Predicting species richness of ectoparasites of wild rodents from the Rio de la
Plata coastal wetlands, Argentina.
AB - The richness of ectoparasite species associated with Sigmodontinae rodents
(Cricetidae) from different sites located in the coastal wetlands of the Rio de
la Plata in Argentina was predicted by a model with three components: (1) habitat
type, considered analogous to rodent species; (2) average ectoparasite species
richness on each rodent species, and (3) average number of rodent species
parasitized by each ectoparasite species. The model, based on rodent information
(number of species and total number of captured rodents) and the environmental
gradient, has a reasonably good fit for the observed data as well as independent
data from different localities. The model is predictive and robust, and it could
be a useful tool for epidemiological and biodiversity management strategies.
Furthermore, the model could be adapted to other habitats if a suitable estimate
of an environmental gradient is found, and it could be also possible to adapt it
to other host taxa.
PMID- 29948206
TI - A review of wildlife tourism and meta-analysis of parasitism in Africa's national
parks and game reserves.
AB - The recent increase of parasitic diseases associated with wildlife tourism can be
traced to human contact with wildlife and intense modification of wildlife
habitat. The continental estimates of parasitic diseases among visited wildlife
tourists and mammalian wildlife present in conservation areas are lacking;
therefore, a general review was necessary to provide insights into Africa's
parasitic disease burden and transmission between humans and wildlife. A two-step
analysis was conducted with searches in Ovid MEDLINE, EMBASE, PubMed, Web of
Science and Global Health. All diseases reported without prevalence were grouped
and analysed as categorical data while meta-analysis of prevalence rates of
parasitic diseases in wildlife from national parks and reserves in Africa was
conducted. Only 4.7% of the tourist centres reported routine wildlife diagnosis
for parasitic diseases. Disease intensity shows that cryptosporidiosis and seven
other parasitic diseases were observed in both human and wildlife; however, no
significant difference in intensity between human and wildlife hosts was
observed. Schistosomiasis intensity reports showed a significant increase (P <
0.05) while entamoebiasis showed a significant decrease (P < 0.05) in humans as
compared to wildlife. Visiting tourists were more infected with malaria, while
wildlife was more infected with parasitic gastroenteritis (PGE). The meta
analysis of wildlife revealed the highest prevalence of PGE with mixed parasites
and lowest prevalence of Giardia spp. at 99.9 and 5.7%, respectively. The
zoonotic and socioeconomic impact of some of these parasites could pose a severe
public threat to tourism. Pre- and post-travel clinical examinations are
important for tourists while routine examination, treatment and rational
surveillance are important for these animals to improve wildlife tourism.
PMID- 29948207
TI - Seasonal variation of Fasciola hepatica antibodies in dairy herds in Northern
Ireland measured by bulk tank milk ELISA.
AB - Bovine fasciolosis, caused by the infection of the trematode parasite Fasciola
hepatica, remains a problem in dairy herds causing significant production losses.
In this study, bulk milk tank samples were utilised to generate a comprehensive
survey of the variation in liver fluke exposure over the four seasons of 2016 in
Northern Ireland (NI). Samples were tested using an antibody ELISA test; within
herd prevalence levels were categorised relative to sample-to-positive ratio
(S/P%). Overall, 1494 herds (~ 50% of all active dairy farms in NI) were sampled.
In total, 5750 samples were tested with 91% of herds having a sample result for
each season. The proportion of herds with evidence of liver fluke exposure was
very high across the year, with 93.03% of all bulk milk samples having some
indication of liver fluke antibody presence. A high proportion of samples
(2187/5750; 38.03%) fell within the highest infection class (indicating high
within-herd prevalence). There was significant seasonal variation in the mean
S/P%. A multivariable random effect ordinal logit model suggested that the
greatest probability of being in a higher infection class was in winter, whilst
the lowest was recorded during summer. There was a significant negative
association between increasing herd liver fluke infection class and herd size.
Furthermore, there was significant variation in infection levels across regions
of Northern Ireland, with higher infection levels in northern administrative
areas. This study demonstrates the very high liver fluke exposure in this region
of Europe, and that risk is not equally distributed spatially or across seasons
in dairy herds.
PMID- 29948208
TI - Update of the helminth fauna in Eurasian lynx (Lynx lynx) in Poland.
AB - The Eurasian lynx (Lynx lynx) is a strictly protected species of large carnivore
in Poland. It inhabits forest complexes in north-eastern Poland and the
Carpathian region in southern Poland. The status of the lynx within Poland
requires special attention because its range decreased between 1980 and 2001 and
has not yet recovered. One of the factors negatively affecting lynx populations
is diseases, particularly parasites. The helminth fauna of the Eurasian lynx is
not fully known in Poland. Previous coprological studies revealed that Polish
lynx have been infected with seven species of nematodes, three species of
cestodes, and one species of trematode. In this study, we present new data based
on examination of opportunistically collected lynx carcasses. The aim of the
study was to complement data on the helminth fauna of Eurasian lynx inhabiting
Poland based on morphological and molecular analysis of parasites. Four species
of cestodes-Taenia lynciscapreoli, Mesocestoides lineatus, Spirometra sp., and
Taenia krabbei-were found for the first time in Eurasian lynx from Poland and
three previously reported species of nematodes-Ancylostoma tubaeforme, Toxascaris
leonina, and Toxocara cati-were confirmed. Larvae of Trichinella britovi were
also detected in Eurasian lynx in Poland for the first time.
PMID- 29948209
TI - Thelohanellus gabori sp. nov. (Myxosporea: Myxozoa) infecting gill filaments of a
Cyprinid fish Crossocheilus latius (Hamilton, 1822) inhabiting a cold water
wetland in Punjab (India).
AB - A new myxobolid, Thelohanellus gabori (Myxosporea: Myxozoa) parasitizing gill
filaments of Crossocheilus latius (Hamilton, 1822) has been described using light
microscopy, histopathology, and molecular analyses. A total of 80 live specimens
of C. latius were examined, revealing a prevalence of infection of 25.66% (21 of
80 fish sampled). The plasmodia were of intrafilamental epithelial type, FE as
per their location in the gill filaments of the fish host. The plasmodia were
cylindrical and creamy-white, 1.0-1.7 mm in diameter containing about 500-700
myxospores. The myxospores had a mean length of 8.56 +/- 0.21 MUm, width 3.66 +/-
0.08 MUm, mean length of polar capsule 5.50 +/- 0.28 MUm, and width 2.50 +/- 0.14
MUm. The 18S rDNA of Thelohanellus gabori sp. nov. (accession number KX757025)
clustered phylogenetically with other related myxozoan parasites being T.
pathankotensis and T. boggoti the most closely related species with 97% sequence
similarity followed by T. sp. FCO with 89% sequence similarity. The mean
abundance (gill plasmodial index) was calculated by counting the number of
plasmodia on each side of the gill apparatus per host and was found to be 4
indicating severe infection causing fusion of many large-sized plasmodia in the
gill filament. During the present study, it was found that the phylogenetic tree
for Thelohanellus spp. depends upon the tissue location, vertebrate host group,
and geographical region.
PMID- 29948210
TI - Efficient production of (R)-(-)-2-hydroxy-4-phenylbutyric acid by recombinant
Pichia pastoris expressing engineered D-lactate dehydrogenase from Lactobacillus
plantarum with a single-site mutation.
AB - (R)-2-hydroxy-4-phenylbutyric acid (R-HPBA) is a valuable intermediate for the
synthesis of angiotensin-converting enzyme inhibitors. The asymmetric reduction
of 2-oxo-4-phenylbutyric acid (OPBA) by oxidoreductases is an efficient approach
for its synthesis. Here, we report a novel biocatalytic approach for asymmetric
synthesis of R-HPBA using recombinant Pichia pastoris expressing the Tyr52Leu
variant of D-lactate dehydrogenase (D-LDH) from Lactobacillus plantarum. The
recombinant yeast cells showed impressive catalytic activity at a high
concentration of NaOPBA (380 mM, 76 g/L) and achieved full conversion starting
with 40 g/L NaOPBA or even at higher concentration. Under optimized reaction
conditions (pH 7.5, 37 degrees C, and 2% glucose), a full conversion with > 95%
reaction yield and ~ 100% product enantiomeric excess (ee) was achieved for the
preparation of R-HPBA on a 2-g scale. The findings of this study promote both the
biotransformation of R-HPBA and an extension of the application of recombinant
yeast as biocatalysts.
PMID- 29948211
TI - BadGluc, a beta-glucosidase from Bjerkandera adusta with anthocyanase properties.
AB - A glycosidase of the basidiomycete Bjerkandera adusta (BadGluc) was found in
screenings to possess a strong decolorizing ability towards malvidin-3
galactoside, an anthocyanin abundant in various berry fruits. The BadGluc was
purified from the culture supernatant via FPLC, and the corresponding gene was
identified which showed low similarity to other characterized glucosidases.
Scanning the primary sequence with PROSITE no active site motif was detected.
Eventually, a specific 18 aa consensus pattern was identified manually. The
active site motif possessed an undescribed sequence which was only found in a few
hypothetical proteins. The corresponding gene was cloned and expressed in Pichia
pastoris GS115 yielding activities up to 100 U/L using 4-nitrophenyl-beta-d
glucopyranoside (pNPG) as substrate. The enzyme possessed a good temperature (70%
after 1 h at 50 degrees C) and pH stability (70% between pH 2 and 7.5), and
preferably catalysed the hydrolysis of delphinidin-3-glucoside and cyanidin-3
glucoside, regardless of the position of the terminal Hexa-His tag. This novel
glucosidase worked in aqueous solution as well as on pre-stained fabrics making
it the first known candidate anthocyanase for applications in the detergent and
food industries.
PMID- 29948212
TI - Enhanced production of carotenoids using a Thraustochytrid microalgal strain
containing high levels of docosahexaenoic acid-rich oil.
AB - Results to date suggest that microalgal Thraustochytrids family strains can be
used to produce high-functional omega-3 rich oil (~ 30-70% of dry cell weight)
and carotenoid-based antioxidant pigments simultaneously with value-added
bioactive potential. In the present study, we describe the isolation and
characterization of a new Thraustochytrid Schizochytrium sp. from the west
coastal area of Korea. This newly isolated Thraustochytrid, identified as
Schizochytrium sp. through 18S rRNA analysis and named SH104, simultaneously
produces high levels of DHA and carotenoid-based antioxidant pigments. An
improved Schizochytrium mutant, named SHG104, was obtained from the original host
strain by gamma-irradiation-induced mutagenesis. Under combined temperature-shift
cultivation conditions employing white-light LEDs (light-emitting diodes),
Schizochytrium sp. SHG104 yielded 10.8 g L-1 of biomass comprising 45.8% total
lipids (32.1% DHA) and 4.6 mg L-1 of astaxanthin. In addition to DHA, the main
fatty acids produced by Schizochytrium sp. SHG104 were palmitic acid and a trace
of other long-chain fatty acids. The carotenoid profile of SH104 and SHG104 was
beta-carotene, astaxanthin, canthaxanthin, pheonicoxanthin and echinenone, which
analyzed by HPLC and LC/APCI-MS. Furthermore, genomic analysis of Schizochytrium
and Aurantiochytrium microalgae confirmed that the presence of carotenogenesis
pathway enzymes and genes including geranylgeranyl diphosphate, phytoene
synthase, lycopene cyclase, and cytochrome P450 hydroxylase that necessary for
the production of antioxidants via a complete biosynthetic KEGG synthesis
pathway. This newly isolated Schizochytrium microalga potentially have wide
application as a source of antioxidants for astaxanthin-containing pigments,
commercial omega-3 lipids and feed additives, such as nutritional supplements for
aquaculture.
PMID- 29948213
TI - Hydrodynamic investigation of a novel shear-generating device for the measurement
of anchorage-dependent cell adhesion intensity.
AB - Proliferation of anchorage-dependent cells occurs after adhesion to a suitable
surface. Thus, quantitative information about the force of cells adhesion to
microcarriers at early culture phases is vital for scaling up such system. In
this work, a newly designed shear-generating device was proposed, based on a
previously proposed contraction flow device designed for suspended cells. A
design equation for the new device was also proposed to correlate the generated
energy dissipation rate (EDR) with the cross-sectional area and flow rate.
Microscopic-particle image velocimetry was measured to validate the simulation
results, and good agreement was achieved. The newly designed device was then used
to measure the adhesion force of MDCK and PK cells, and the results showed that
the critical EDR was 3000 W/m3 for MDCK and 5000 W/m3 for PK cells. This
quantitative information is of great value for better understanding shearing
effects during the scaling up of anchorage-dependent cell cultures.
PMID- 29948214
TI - Improved production of jiangxienone in submerged fermentation of Cordyceps
jiangxiensis under nitrogen deficiency.
AB - Jiangxienone produced by Cordyceps jiangxiensis exhibits significant cytotoxicity
and good selectivity against various human cancer cells, especially gastric
cancer cells. In this work, the effect of nitrogen deficiency on the accumulation
of jiangxienone and the transcription levels of jiangxienone biosynthesis genes
was studied in submerged fermentation of C. jiangxiensis. Results showed that
accumulation of jiangxienone was improved under nitrogen deficiency condition. A
maximal jiangxienone content of 3.2 ug/g cell dry weight was reached at 5 mM
glutamine, and it was about 8.9-fold higher than that obtained at 60 mM glutamine
(control). The transcription levels of the biosynthetic pathway genes hmgr and
sqs and the nitrogen regulatory gene areA were upregulated by 7-, 14-, and 28
fold, respectively, in culture with 5 mM glutamine compared to the control. It
was hypothesized that the jiangxienone biosynthesis may involve the mevalonate
pathway in C. jiangxiensis. Taken together, our study indicated that nitrogen
deficiency is an efficient strategy for enhancing jiangxienone accumulation in
submerged fermentation of C. jiangxiensis, which is useful for further
understanding the regulation of jiangxienone biosynthesis.
PMID- 29948216
TI - Gene expression changes by high-polyphenols cocoa powder intake: a randomized
crossover clinical study.
AB - PURPOSE: To assess the effect of the intake of a single dose of high-polyphenols
cocoa on gene expression in peripheral mononuclear cells (PBMCs), and analyze
conjugated (-)-epicatechin metabolites in plasma, which may be related with an
antioxidant response in healthy human. METHODS: A randomized, controlled, double
blind, cross-over, clinical trial in healthy young adults who consumed a single
dose of high-polyphenols cocoa powder and maltodextrins as control, with a one
week washout period. Analysis of circulating metabolites, plasma antioxidant
capacity and gene expression changes in PBMCs were performed under fasting
conditions and 2-h after treatment using microarray in a subsample. Pathway
analysis was conducted using Ingenuity Pathway Analysis (IPA). RESULTS: Twenty
healthy participants (9 F) were included in the study. A significant increase in
circulating (-)-epicatechin metabolites was found after cocoa intake in all
participants without related changes in antioxidant capacity of plasma. The
metabolites profile slightly varied across subjects. Treatments triggered
different transcriptional changes in PBMC. A group of 98 genes showed changes in
expression after cocoa treatment, while only 18 were modified by control.
Differentially expressed genes included inflammatory cytokines and other
molecules involved in redox balance. Gene and network analysis after cocoa intake
converged in functions annotated as decreased production of reactive oxygen
species (p = 9.58E-04), decreased leukocyte activation (p = 4E-03) and calcium
mobilization (p = 2.51E-05). CONCLUSIONS: No association was found between
conjugated metabolites in plasma and antioxidant capacity. Changes in PBMCs gene
expression suggest anti-inflammatory effects.
PMID- 29948215
TI - Improving techno-economics of bioproduct glycolic acid by successive recycled
cell catalysis of ethylene glycol with Gluconobacter oxydans.
AB - Bioconversion of ethylene glycol (EG) to glycolic acid (GA) by the whole-cell of
Gluconobacter oxydans in an aired stirred tank reactor (ASTR) with continuous
substrate feeding yielded over 220 g/L of GA. However, the bioreactor
productivity declined to an unfavorable level of 0.63 g/L/h due to negative feed
back by GA which inhibited the reaction. To overcome this problem, based on
results obtained from techno-economic comparative analysis, we set up a
successive recycled-cell catalytic bioprocessing ASTR, and carried out five
consecutive cycles stably during 240 h. At the end of this process, total 490.7 g
GA was accumulated with over 90% yield, and an average bioreactor productivity of
2.04 g/L/h. The twin strategies of end-product titer control and cell-recycling
successfully demonstrated the large scale applicability of EG bioconversion to
GA.
PMID- 29948217
TI - Iron bioavailability of four iron sources used to fortify infant cereals, using
anemic weaning pigs as a model.
AB - PURPOSE: Iron (Fe) deficiency anemia in young children is a global health concern
which can be reduced by Fe fortification of foods. Cereal is often one of the
first foods given to infants, providing adequate quantities of Fe during weaning.
In this work, we have compared iron bioavailability and iron status of four iron
sources used to fortify infant cereals, employing piglets as an animal model.
METHOD: The study was conducted on 36 piglets, 30 of them with induced anemia.
From day 28 of life, the weaned piglets were fed with four experimental diets (n
= 6) each fortified with 120 mg Fe/kg by ferrous sulfate heptahydrate (FSH),
electrolytic iron (EI), ferrous fumarate (FF), or micronized dispersible ferric
pyrophosphate (MDFP) for another 21 days. In addition, one group of six anemic
piglets fed with the basal diet with no iron added (Control-) and a Control+
group of non-anemic piglets (n = 6) were also studied. Blood indicators of iron
status were measured after depletion and during the repletion period. The Fe
content in organs, hemoglobin regeneration efficiency, and relative
bioavailability (RBV) was also determined. RESULTS: The Fe salts adequately
treated anemia in the piglets, allowing the animals to recover from the anemic
state, although EI was less efficient with regard to replenishing Fe stores
giving lower concentrations of plasma ferritin and iron in the spleen, liver,
lung, and kidney. In addition, the RBV of EI was 88.27% with respect to the
reference iron salt (FSH). CONCLUSIONS: Ferrous fumarate and MDFP were equally as
bioavailable as the reference salt, and were used significantly better than EI in
piglets. These results contribute to extend the evidence-based results for
recommending the most suitable fortificant for infant cereals.
PMID- 29948219
TI - The independent associations of protein consumption with body fat and glycaemic
control in adult Chinese.
AB - PURPOSE: High-protein diets were popular in weight control. However, the role of
protein intake in adiposity and related metabolic conditions among general
populations is not clear. We aimed to evaluate the associations of protein intake
with adiposity and glycaemic control among adult Chinese in a nationwide
population-based survey. METHODS: The data were from China Health and Nutrition
Survey 2009. A total of 9360 men and women aged 18 years or older were included.
Body fat percentage was calculated using validated Chinese-specific equations.
Dietary intake levels of macronutrients were evaluated by food-weighing approach
combined with a 3-day food intake recall. RESULTS: Averagely, our participants
have 12.5% energy intake from dietary protein. With multivariate adjustment
including total energy intake, the odds ratios (95% CIs) of excessive adiposity
(body fat percentage >= 20/30% for men/women), and central obesity (waist
circumference >= 90/80 cm for men/women) were 1.51 (1.30, 1.75) and 1.40 (1.21,
1.62), respectively, comparing extreme quintiles of relative protein intake,
while fat and carbohydrate were not associated with adiposity indices. Moreover,
higher relative protein intake was associated with elevated concentration of
fasting glucose (beta +/- SE: 1.233 +/- 0.583), fasting insulin (23.211 +/-
9.191), glycated hemoglobin (1.057 +/- 0.369), and insulin resistance indicated
by homeostasis model assessment of insulin resistance (7.558 +/- 2.928) (all P <
0.05). Further adjusting for body mass index attenuated the associations.
CONCLUSION: In Chinese adults, higher habitual protein consumption may be
associated with higher adiposity and worse glycaemic control, independent of
total energy intake.
PMID- 29948218
TI - Net contribution and predictive ability of the CUN-BAE body fatness index in
relation to cardiometabolic conditions.
AB - BACKGROUND: The CUN-BAE (Clinica Universidad de Navarra-Body adiposity estimator)
index is an anthropometric index based on age, sex and body mass index (BMI) for
a refined prediction of body fatness in adults. CUN-BAE may help detect
metabolically unhealthy individuals with otherwise normal weight according to BMI
or waist circumference (WC). The aim of this study was to evaluate whether CUN
BAE, independent of its components (BMI, age and sex), was associated with
cardiometabolic conditions including arterial hypertension, diabetes mellitus and
metabolic syndrome (MetS). METHODS: The ENRICA study was based on a cross
sectional sample of non-institutionalized men and women representative of the
adult Spanish population. Body weight, height, and WC were measured in all
participants. The residual of CUN-BAE (rCUN-BAE), i.e. the part of the index not
explained by its components, was calculated. The associations of CUN-BAE, rCUN
BAE, BMI and WC with hypertension, diabetes and MetS were analysed by
multivariate logistic regression, and the Akaike information criterion (AIC) was
calculated. RESULTS: The sample included 12,122 individuals. rCUN-BAE was
associated with hypertension (OR 1.14, 95% CI 1.07-1.21) and MetS (OR 1.48, 1.37
1.60), but not with diabetes (OR 1.05, 0.94-1.16). In subjects with a BMI < 25
kg/m2, CUN-BAE was significantly associated with all three outcome variables. CUN
BAE was more strongly associated with the cardiometabolic conditions than BMI and
WC and fit similar AICs. CONCLUSIONS: The CUN-BAE index for body fatness was
positively associated with hypertension, diabetes and MetS in adults independent
of BMI or WC. CUN-BAE may help to identify individuals with cardiometabolic
conditions beyond BMI, but this needs to be confirmed in prospective settings.
PMID- 29948220
TI - Egg consumption and prevalence of psychological disorders in adults.
AB - PURPOSE: No previous study has examined the associations between egg consumption
and prevalence of psychological disorders. The present study was conducted to
determine the association between egg consumption and depression in a large
sample of Iranian adults. METHODS: This cross-sectional study was conducted on
3172 adults in Isfahan, Iran. Egg consumption was assessed by using a validated,
self-administered, dish-based, semi-quantitative food frequency questionnaire.
The Iranian validated version of Hospital Anxiety and Depression Scale was used
to screen for anxiety and depression. The Iranian validated version of General
Health Questionnaire with 12 items was used to assess psychological distress.
Depression, anxiety and psychological distress were defined according to standard
criteria. RESULTS: The mean age of the study participants was 36.5 +/- 7.9 years.
Depression, anxiety and psychological distress were prevalent among 28.4, 13.6
and 23% of the study subjects, respectively. After controlling for potential
confounders, no significant association was observed between egg intake and
depression (OR for comparing extreme quartiles: 1.08; 95% CIs 0.80-1.45) and
anxiety (OR 0.79; 95% CIs 0.54-1.16), as well as psychological distress (OR 1.03;
95% CIs 0.76-1.41) in the whole population. In men, significant positive
associations were observed between egg intake and depression before controlling
for BMI (OR 1.68; 95% CIs 1.01-2.80); however, the associations became non
significant after taking BMI into account (OR 1.62; 95% CIs 0.96-2.72).
CONCLUSIONS: We found no significant association between egg intake and
psychological disorders. Further studies, in particular of prospective design,
are warranted.
PMID- 29948221
TI - An integrated transcriptomic and epigenomic analysis identifies CD44 gene as a
potential biomarker for weight loss within an energy-restricted program.
AB - PURPOSE: The interindividual variable response to weight-loss treatments requires
the search for new predictive biomarkers for improving the success of weight-loss
programs. The aim of this study is to identify novel genes that distinguish
individual responses to a weight-loss dietary treatment by using the integrative
analysis of mRNA expression and DNA methylation arrays. METHODS: Subjects from
Metabolic Syndrome Reduction in Navarra (RESMENA) project were classified as low
(LR) or high (HR) responders depending on their weight loss. Transcriptomic (n =
24) and epigenomic (n = 47) patterns were determined by array-based genome-wide
technologies in human white blood cells at the baseline of the treatment period.
CD44 expression was validated by qRT-PCR and methylation degree of CpGs of the
gene was validated by MassARRAY(r) EpiTYPERTM in a subsample of 47 subjects. CD44
protein levels were measured by ELISA in human plasma. RESULTS: Different
expression and DNA methylation profiles were identified in LR in comparison to
HR. The integrative analysis of both array data identified four genes: CD44,
ITPR1, MTSS1 and FBXW5 that were differently methylated and expressed between
groups. CD44 showed higher expression and lower DNA methylation levels in LR than
in HR. Although differences in CD44 protein levels between LR and HR were not
statistically significant, a positive association was observed between CD44 mRNA
expression and protein levels. CONCLUSIONS: In summary, the combination of a
genome-wide methylation and expression array dataset can be a useful strategy to
identify novel genes that might be considered as predictors of the dietary
response. CD44 gene transcription and methylation may be a possible candidate
biomarker for weight-loss prediction.
PMID- 29948222
TI - Diet as moderator in the association of adiposity with inflammatory biomarkers
among adolescents in the HELENA study.
AB - AIM: Our aim is to demonstrate that a healthy diet might reduce the relation
between adiposity and inflammation, whereas an unhealthy diet may increase the
effect of adiposity on inflammatory biomarkers. METHODS: In 618 adolescents (13
17 years) of the European HELENA study, data were available on body composition,
a set of inflammation markers, and food intake determined by a self-administered
computerized 24-h recall. A 9-point Mediterranean diet score and an antioxidant
rich diet score were used as dietary parameters and tested as moderator. Total
body fat was represented by the sum of six skinfold thicknesses and central
adiposity by waist circumference. A set of inflammation-related biomarkers was
used as outcome: a pro/anti-inflammatory interleukins ratio, TGFbeta-1, C
reactive protein, TNF-alpha, 3 cell adhesion molecules, and 3 types of immune
cells; gamma-glutamyltransferase (GGT) and homocysteine were used as
cardiovascular disease risk biomarkers, and alanine transaminase (ALT) as liver
dysfunction biomarker. Multiple linear regression analyses tested moderation by
diet in the adiposity-inflammation association and were adjusted for age, sex,
country, puberty, socioeconomic status. RESULTS: Both the Mediterranean and
antioxidant-rich diet, and overall and central adiposity, were important in the
moderation. Diet was a significant protective moderator in the effect of
adiposity on the pro/anti-inflammatory interleukins ratio, TGFbeta-1, GGT, and
ALT. CONCLUSION: In conclusion, in some cases, a diet rich in antioxidants and
essential nutrients may attenuate the concentration of inflammatory biomarkers
caused by adiposity, whereas a poor diet appears to contribute to the onset of
early oxidative stress signs.
PMID- 29948223
TI - Does patella alta lead to worse clinical outcome in patients who undergo isolated
medial patellofemoral ligament reconstruction? A systematic review.
AB - INTRODUCTION: The aim of this systematic review is to determine the effect of
patella height on clinical outcomes after isolated MPFL reconstruction for
patella instability. Our primary hypothesis is that patients with patella alta
report similar outcomes after isolated MPFL reconstruction compared to patients
with normal patella height. METHODS: A review of the literature was performed
according to the PRISMA guidelines. PubMed, EMBASE, and the Cochrane Library were
searched from inception to January 10th 2018. Studies were identified using
synonyms for "medial patellofemoral ligament", "reconstruction" and "patella
alta". RESULTS: The search resulted in 467 reports on PubMed, 175 on EMBASE and 3
on the Cochrane Library. We included and analyzed in detail six studies
describing outcomes after isolated medial patellofemoral ligament reconstruction
with regard to patellar height. We found that both patients with patella alta and
normal patella height reported satisfactory outcomes after isolated medial
patellofemoral ligament reconstruction. However, because of applied exclusion
criteria in the included studies the total number of patients with severe patella
alta was small (13/74 patients with patella alta, 18%). CONCLUSIONS: Based on the
current literature we suggest that additional tibial tubercle distalisation is
not mandatory in patients with mild patella alta (Caton-Deschamps Index 1.2-1.4).
To assess the best indications for different surgical procedures for patients
with patella instability future research is needed to develop a clear and uniform
definition of relevant patella alta. LEVEL OF EVIDENCE: III.
PMID- 29948224
TI - Fluid collection bags pose a threat for bacterial contamination in primary total
hip arthroplasty: a prospective, internally controlled, non-blinded trial.
AB - INTRODUCTION: Surgical equipment, and especially the so-called 'splash basins'
that are used intraoperatively, are a potential source of bacterial contamination
in primary total hip arthroplasty (THA). With this risk in mind, many
commercially available draping kits include plastic bags that can be used to
collect fluid or to temporarily store instruments. Following this rationale, we
hypothesised that first: the fluid collection bags are a potential reservoir of
bacteria and second: there is a time dependency for bacterial contamination.
MATERIALS AND METHODS: After ethics approval, we investigated in a prospective,
internally controlled, non-blinded trial 43 patients who received primary THA. At
the beginning of the surgery, we took deep, representative, intracapsular tissue
samples, which served as negative controls. At the end of surgery, tissue samples
were taken from the bottom of the 'fluid collection bag' for microbiological
analysis. RESULTS: All 86 control samples were negative. Out of the samples taken
from the bags, a pathogen could be detected in four patients (9.3%). All
pathogens were detected after a surgery time lasting longer than 90 min.
CONCLUSION: We were able to show that fluid collection bags are a potential
reservoir for bacteria in THA when surgery time was greater than a 90-min
threshold. Our data suggest that the risks from fluid collection bags outweigh
the advantages of using them. Therefore, we recommend against the use of fluid
collection bags intraoperatively in primary THA.
PMID- 29948225
TI - Mid-term clinical results of an arthroscopic glenoid rim reconstruction technique
for recurrent anterior shoulder instability.
AB - INTRODUCTION: Glenoid bone loss in recurrent anterior instability of the shoulder
needs to be addressed to restore joint stability. Over the last years, several
arthroscopic methods have been described to treat this condition. However, no
clinical mid-term results have been presented for arthroscopic iliac crest bone
grafting procedures. METHODS: We included 32 patients with significant glenoid
bone loss and repetitive dislocations of the shoulder who were treated in our
shoulder unit with a previously described all-arthroscopic reconstruction
technique. All patients filled out a questionnaire evaluating repetitive
dislocations, consumption of pain medicine, Constant Score (CS, adapted to age
and gender), activities of daily living (ADL), visual analogue scale for pain
(VAS) as well as the Western Ontario Shoulder Instability Index (WOSI).
Additionally, all complications were recorded. RESULTS: After a mean follow-up of
42 months, three traumatic dislocations had been observed. With an ADL of 25
points (95% CI 24-27), a WOSI of 71% (95% CI 65-76) and CS of 87 points (95% CI
82-92), our patients showed good functional results. The VAS result for pain was
2.1 (95% CI 1.5-2.6). No patient reported the regular usage of pain medicine
related to the shoulder instability at final follow-up. CONCLUSION: The all
arthroscopic glenoid reconstruction using iliac crest grafts shows good
functional results with a recurrence rate of 9%. At final follow-up 42 months
after surgery, our patients showed low pain levels and acceptable complications.
PMID- 29948226
TI - One-year outcome following brain injury: a comparison of younger versus elderly
major trauma patients.
AB - INTRODUCTION: The increasing number of older trauma patients has provoked a
debate on the need for subsequent rehabilitative therapy for the elderly. Our
findings revealed a lack of detailed data on this topic so we became interested
in the effective differences in the longer-term outcomes for older and younger
major trauma patients with TBI. As validation studies on the recently published
specific Quality of Life after Brain Injury (QOLIBRI) have only involved patients
under the age of 68 years, we focused on testing this score in comparison to
other outcome measures. MATERIALS AND METHODS: Prospective cohort study of the
differences in 1-year functional or health-related quality of life (HRQoL)
outcomes, such as the Glasgow Outcome Score (GOS), the Quality of Life after
Brain Injury (QOLIBRI) score or the medical outcomes study Short Form-36 (SF-36)
between younger (16-64 years) and elderly (> 65 years) adults following major
trauma (New Injury Severity Score, NISS >= 8) with TBI (Abbreviated Injury Scale,
AIS head > 0). RESULTS: Out of 326 TBI patients with a mean NISS of 20.6 +/- 9.4
34% (n = 110 (33.7%)) were aged 65 or older versus n = 216 (66.3%) who were
younger. Comparison of 1-year outcomes revealed no differences between younger
versus elderly patients with regard to functional or HRQoL scores (e.g. total
QOLIBRI 77.4 +/- 20.0 and 75.6 +/- 18.1, resp.). Univariate analysis showed no
correlation of the total QOLIBRI with age (Pearson r = - 0.09) or trauma severity
(AIS) of the head (r = - 0.05). Multivariate analysis confirmed an association of
age 80 or older (R2 = 0.026, p = 0.029), but not of overall age (R2 = 0.004, p =
0.218) with 1-year outcome scores on the total QOLIBRI. CONCLUSIONS: Given the
rising rehabilitation demands of the elderly these pilot findings call for the
utilisation of specific outcome scores such as the QOLIBRI in this age group as
well, at least up to an age of 80 years and independently of the severity of TBI
sustained.
PMID- 29948227
TI - Better rotational control but similar outcomes with the outside-in versus the
transtibial drilling technique for anterior cruciate ligament reconstruction: a
systematic review of comparative trials.
AB - INTRODUCTION: This study was a systematic review comparing the clinical outcomes
of using the transtibial (TT) versus the outside-in (OI) technique for anterior
cruciate ligament (ACL) reconstruction. MATERIALS AND METHODS: A comprehensive
literature search was conducted using multiple databases, including Medline,
Embase, and Cochrane. All databases were searched from the earliest records
through August 2017 using the following Boolean operators: transtibial AND
(outside-in OR out-in OR two incisions) AND anterior cruciate ligament. All
prospective and retrospective controlled trials were retrieved that directly
compared physical examination and knee function scores and patient-rated outcomes
between the TT and OI techniques. RESULTS: Four prospective and three
retrospective articles were identified by the search, and the findings suggested
that the OI was superior to the TT technique for preparing the femoral tunnel
based on the pivot shift test (p = 0.05). There was no statistically significant
difference between the two treatment groups in International Knee Documentation
Committee (IKDC) grades, IKDC scores, Lysholm scores, Tegner scores, or the
Lachman test. CONCLUSIONS: No statistically significant differences were found in
clinical functional results when comparing patients who underwent ACL
reconstruction with the TT or OI techniques. However, the OI technique was found
to be advantageous in conferring increased rotational stability as revealed by
the pivot shift test. Additional studies with larger sample sizes are needed to
make more precise conclusions. LEVEL OF EVIDENCE: Therapeutic study (systematic
review), Level III.
PMID- 29948228
TI - Treatment of child externalizing behavior problems: a comprehensive review and
meta-meta-analysis on effects of parent-based interventions on parental
characteristics.
AB - This is the first meta-meta-analysis examining the effects of parent-based
interventions for children with externalizing behavior problems on parental
characteristics (parenting, parental perceptions, parental mental health,
parental relationship quality). Parent training interventions are recognized as
evidence-based interventions for the treatment of externalizing behavior
problems, although meta-analytic effects are heterogeneous. The objective of the
present study was to comprehensively combine meta-analytic results on parent
training interventions to arrive at valid effect predictions. Electronic
databases were searched (PsycINFO, Medline, PubMed). In total, 11 meta-analyses
were included that mainly comprised parents of children under the age of 13
years. Analyses were based on random effects models. Effect estimates were
transformed to standardized mean differences (SMD) and corrected for primary
study overlap. Results revealed a significant moderate overall effect for
parenting (SMD 0.53) as well as for parents' report of parenting (SMD 0.60) and
parental perceptions (SMD 0.52). Effects remained stable to follow-up. Results
for observational data, parental mental health and parental relationship quality
were small and only partially significant. Considerable heterogeneity within
results was revealed. Overall, parent training interventions proved to be
effective in improving parental characteristics for parents of children with
externalizing behavior problems. Effectiveness was stronger regarding
characteristics explicitly targeted by interventions. The findings should
encourage health-care providers to apply evidence-based parent training
interventions.
PMID- 29948229
TI - Correction to: Prevalence of pica and rumination behaviors in German children
aged 7-14 and their associations with feeding, eating, and general
psychopathology: a population-based study.
AB - n the original publication, under the discussion section.
PMID- 29948231
TI - Prevalence of war-related adverse events, depression and anxiety among Syrian
refugee children settled in Turkey.
PMID- 29948230
TI - Conduct disorder in adolescent females: current state of research and study
design of the FemNAT-CD consortium.
AB - Conduct disorder (CD) is a common and highly impairing psychiatric disorder of
childhood and adolescence that frequently leads to poor physical and mental
health outcomes in adulthood. The prevalence of CD is substantially higher in
males than females, and partly due to this, most research on this condition has
used all-male or predominantly male samples. Although the number of females
exhibiting CD has increased in recent decades, the majority of studies on
neurobiological measures, neurocognitive phenotypes, and treatments for CD have
focused on male subjects only, despite strong evidence for sex differences in the
aetiology and neurobiology of CD. Here, we selectively review the existing
literature on CD and related phenotypes in females, focusing in particular on sex
differences in CD symptoms, patterns of psychiatric comorbidity, and callous
unemotional personality traits. We also consider studies investigating the
neurobiology of CD in females, with a focus on studies using genetic, structural
and functional neuroimaging, psychophysiological, and neuroendocrinological
methods. We end the article by providing an overview of the study design of the
FemNAT-CD consortium, an interdisciplinary, multi-level and multi-site study that
explicitly focuses on CD in females, but which is also investigating sex
differences in the causes, developmental course, and neurobiological correlates
of CD.
PMID- 29948234
TI - The impact of maternal prenatal and postnatal anxiety on children's emotional
problems: a systematic review.
AB - Maternal mental health problems during pregnancy and the postnatal period are a
major public health issue. Despite evidence that symptoms of both depression and
anxiety are common during pregnancy and the postpartum, the impact of maternal
anxiety on the child has received relatively less attention than the impact of
maternal depression. Furthermore, the evidence base for the direct impact of
maternal anxiety during pregnancy and the postpartum on children's emotional
outcomes lacks cohesion. The aim of this systematic review is to summarise the
empirical evidence regarding the impact of maternal prenatal and postnatal
anxiety on children's emotional outcomes. Overall, both maternal prenatal and
postnatal anxiety have a small adverse effect on child emotional outcomes.
However, the evidence appears stronger for the negative impact of prenatal
anxiety. Several methodological weaknesses make conclusions problematic and
replication of findings is required to improve the identification of at-risk
parents and children with appropriate opportunities for intervention and
prevention.
PMID- 29948233
TI - Child-based treatment of oppositional defiant disorder: mediating effects on
parental depression, anxiety and stress.
AB - Previous research has shown that child-oppositional defiant disorder (ODD) and
conduct disorders (CD) are associated with parental symptoms of depression,
anxiety and/or stress, probably in a bidirectional relationship with mutual
influences. It is, therefore, reasonable to assume that in child-centered
treatment, a decrease in child-oppositional behavior problems constitutes (at
least in part) a mechanism of change for a subsequent reduction in parental
psychopathology. The aim of the present study (Clinical trials.gov Identifier:
NCT01406067) was to examine whether the reduction in ODD symptoms due to child
based cognitive behavioral treatment (CBT) led to a reduction in parental
depression, anxiety and stress. Eighty-one boys (age 6-12 years) with a diagnosis
of ODD/CD were randomized either to a cognitive behavioral intervention group or
an educational play group (acting as control group). Mediation analyses were
conducted using path analysis. The stronger reduction in child ODD symptoms in
the CBT group compared to the control group led to a decrease in parental
depression and stress, as indicated by significant indirect effects (ab = 0.07
and ab = 0.08, p < 0.05). The proposed model for mechanisms of change was,
therefore, confirmed for two of the three outcome parameters. Parental
psychopathology and stress can be modified by child-centered CBT. The preceding
reduction in ODD symptoms acts as a mediator for at least some of the changes in
parental depression and stress. However, due to some limitations of the study,
other possible explanations for the results found cannot be completely ruled out
and are, therefore, discussed.
PMID- 29948232
TI - Long-term neurodevelopmental consequences of intrauterine exposure to lithium and
antipsychotics: a systematic review and meta-analysis.
AB - Lithium and antipsychotics are often prescribed to treat bipolar disorder or
psychotic disorders in women of childbearing age. Little is known about the
consequences of these medications during pregnancy for the developing child. The
objective of this article is to systematically review findings from preclinical
and clinical studies that have examined the neurodevelopmental consequences of
intrauterine exposure to lithium and antipsychotics. A systematic search was
performed in Embase, Medline, Web of Science, PsychINFO, Cochrane, and Google
Scholar. Clinical and experimental studies were selected if they investigated
neurodevelopment of offspring exposed to lithium or antipsychotics during
gestation. Quality of clinical and preclinical studies was assessed by the
Newcastle-Ottawa Scale and the SYRCLE's risk of Bias tool, respectively. In
total, 73 studies were selected for qualitative synthesis and three studies were
selected for quantitative synthesis. Of preclinical studies, 93% found one or
more adverse effects of prenatal exposure to antipsychotics or lithium on
neurodevelopment or behaviour. Only three clinical cohort studies have
investigated the consequences of lithium exposure, all of which reported normal
development. In 66% of clinical studies regarding antipsychotic exposure, a
transient delay in neurodevelopment was observed. The relative risk for
neuromotor deficits after in utero exposure to antipsychotics was estimated to be
1.63 (95% CI 1.22-2.19; I2 = 0%). Preclinical studies suggest long-term adverse
neurodevelopmental consequences of intrauterine exposure to either lithium or
antipsychotics. However, there is a lack of high-quality clinical studies.
Interpretation is difficult, since most studies have compared exposed children
with their peers from the unaffected population, which did not allow correction
for potential influences regarding genetic predisposition or parental psychiatric
illness.
PMID- 29948235
TI - Characterization and Expression Dynamics of Key Genes Involved in the Gilthead
Sea Bream (Sparus aurata) Cortisol Stress Response during Early Ontogeny.
AB - The present study identified and characterized six key genes involved in the
hypothalamic-pituitary-interrenal (HPI) axis of gilthead sea bream (Sparus
aurata), a commercially important European aquaculture species. The key genes
involved in the HPI axis for which gene structure and synteny analysis was
carried out, comprised of two functional forms of glucocorticoid receptors (GR),
as well as three forms of pro-opiomelanocortin (POMC) genes and one form of
mineralocorticoid receptor (MR) gene. To explore their functional roles during
development but also in the stress response, the expression profiles of gr1, gr2,
mr, pomc_aI, pomc_aII, and pomc_beta were examined during early ontogeny and
after an acute stress challenge. The acute stress challenge was applied at the
stage of full formation of all fins, where whole body cortisol was also measured.
Both the cortisol and the molecular data implied that sea bream larvae at the
stage of the full formation of all fins at 45 dph are capable of a response to
stress of a similar profile as observed in adult fish.
PMID- 29948237
TI - Improvement of 19F MR image uniformity in a mouse model of cellular therapy using
inductive coupling.
AB - OBJECTIVE: Improve 19F magnetic resonance imaging uniformity of perfluorocarbon
(PFC)-labeled cells by using a secondary inductive resonator tuned to 287 MHz to
enhance the induced radio frequency (RF) magnetic field (B1) at 7.05 T. MATERIALS
AND METHODS: Following Faraday's induction law, the sign of induced B1 made by
the secondary resonator can be changed depending on the tuning of the resonator.
A secondary resonator located on the opposite side of the phantom of the 19F
surface coil can be shown to enhance or subtract the induced B1 field, depending
upon its tuning. RESULTS: The numerical simulation results of rotating transmit
B1 magnitude (|B 1+ |) and corresponding experimental 19F images were compared
without and with the secondary resonator. With the secondary resonator tuned to
287 MHz, improvements of |B 1+ | and 19F image uniformity were demonstrated. The
use of the secondary resonator improved our ability to visualize transplanted
cell location non-invasively over a period of 6 weeks. CONCLUSION: The secondary
resonator tuned to enhance the induced B1 results in improved image uniformity in
a pre-clinical application, enabling cell tracking of PFC-labeled cells with the
secondary resonator.
PMID- 29948236
TI - Fast MR thermometry using an echo-shifted sequence with simultaneous multi-slice
imaging.
AB - PURPOSE: Real-time monitoring is important for the safety and effectiveness of
high-intensity focused ultrasound (HIFU) therapy. Magnetic resonance imaging is
the preferred imaging modality for HIFU monitoring, with its unique capability of
temperature imaging. For real-time temperature imaging, higher temporal
resolution and larger spatial coverage are needed. In this study, a sequence
based on the echo-shifted RF-spoiled gradient echo (GRE) with simultaneous multi
slice (SMS) imaging was designed for fast temperature imaging. METHODS: A phantom
experiment was conducted to evaluate the accuracy of the echo-shifted sequence
using a fluorescent fiber thermometer as reference. The temperature uncertainty
of the echo-shifted sequence was compared with the traditional GRE sequence at
room temperature through the ex vivo porcine muscle. Finally, the ex vivo porcine
liver tissue experiment using HIFU heating was performed to demonstrate that the
spatial coverage was increased without decreasing temporal resolution. RESULTS:
The echo-shifted sequence had a better temperature uncertainty performance
compared with the traditional GRE sequence with the same temporal resolution. The
ex vivo heating experiment confirmed that by combining the SMS technique and echo
shifted sequence, the spatial coverage was increased without decreasing the
temporal resolution while maintaining high temperature measurement precision.
CONCLUSION: The proposed technique was validated as an effective real-time method
for monitoring HIFU therapy.
PMID- 29948238
TI - Primary prophylactic granulocyte colony-stimulating factor according to ASCO
guidelines has no preventive effect on febrile neutropenia in patients treated
with docetaxel, cisplatin, and 5-fluorouracil chemotherapy.
AB - BACKGROUND: The efficacy of primary prophylactic granulocyte colony-stimulating
factor (G-CSF) in preventing febrile neutropenia (FN) in patients treated with
docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy remains
controversial. We compared the incidence of FN in patients treated with and
without primary prophylactic G-CSF. METHODS: We performed a retrospective
analysis of 142 patients with locally advanced head and neck or esophageal cancer
treated with TPF between January 2009 and March 2017. Among them, 116 patients
started TPF without primary prophylactic G-CSF (control group) while 26 patients
were given primary prophylactic G-CSF from day 7 of the first cycle of TPF
(prophylactic group). RESULTS: The incidence of grade 4 neutropenia during the
first cycle of TPF was significantly higher in the control group than in the
prophylactic group [58.6% (n = 68) vs. 30.8% (n = 8), p = 0.02]. However, the
incidence of FN in the first cycle was not significantly different between the
two groups [32 patients (27.5%) in the control group and 8 patients (30.8%) in
the prophylactic group (p = 0.62)]. In addition, the mean relative dose intensity
throughout all cycles of TPF, as well as the survival time and response after
TPF, were also not significantly different between the two groups. CONCLUSIONS:
Primary prophylactic G-CSF from day 7 of the first cycle of TPF did not reduce
the incidence of FN. Our findings suggest that the timing of primary prophylactic
G-CSF, as recommended by the American Society of Clinical Oncology guidelines,
should be modified to reduce the incidence of FN in TPF.
PMID- 29948241
TI - Neuromyelitis optica: suicide risk and psychiatric comorbidities.
PMID- 29948240
TI - Colorectal obstruction is a potential prognostic factor for stage II colorectal
cancer.
AB - BACKGROUND: Obstructive colorectal cancer (CRC) is an emergency situation with
high morbidity and mortality, but long-term outcomes of stage II/III obstructive
CRC remain unclear. The aim of this study was to evaluate prognostic factors,
including colorectal obstruction. METHODS: Data were retrospectively reviewed
from consecutive patients with stage II/III CRC who underwent curative surgery
between January 2007 and December 2011 at two Japanese institutions. We analyzed
overall survival (OS) and relapse-free survival (RFS), according to various
prognostic factors including colorectal obstruction. RESULTS: In total, 979
patients with stage II/III CRC were identified for this study. Among these 979
patients, 94 patients showed colorectal obstruction (9.6%). In both stage II and
stage III CRCs, colorectal obstruction showed significantly poorer OS and RFS
compared to non-obstruction (5-year OS, obstruction vs. non-obstruction, stage
II: 65.9 vs. 86.5%, P = 0.002; stage III: 55.9 vs. 73.6%, P = 0.007) (5-year RFS,
obstruction vs. non-obstruction, stage II: 59.2 vs. 77.8%, P = 0.008; stage III
31.3 vs. 56.3%, P = 0.001). Multivariate analysis demonstrated colorectal
obstruction as a significant independent and poor prognostic factor in terms of
both OS (hazard ratio (HR) 2.469; 95% CI 1.339-4.545; P = 0.004) and RFS (HR
1.992; 95% CI 1.160-3.425; P = 0.012) for stage II CRC, as well as pT4 stage. On
multivariate analysis for stage III CRC, colorectal obstruction was a significant
predictor of poor RFS (HR 1.626; 95% CI 1.070-2.469; P = 0.023), but not poor OS.
CONCLUSIONS: Colorectal obstruction is an independent poor prognostic factor for
stage II CRC. Adjuvant chemotherapy might be feasible for stage II CRC with
colorectal obstruction.
PMID- 29948239
TI - Changes in programmed death ligand 1 expression in non-small cell lung cancer
patients who received anticancer treatments.
AB - BACKGROUND: The expression of programmed death ligand 1 (PD-L1) is considered a
predictive biomarker of anti-programmed death 1 (PD-1)/PD-L1 cancer therapies.
However, changes in PD-L1 expression of tumor cells during clinical courses have
not been fully evaluated. We evaluated changes in PD-L1 expression for non-small
cell lung cancer (NSCLC) patients who received anticancer treatments during
clinical courses. METHODS: In 76 NSCLC patients, PD-L1 expression was evaluated
before and after anticancer treatment by immunohistochemical (IHC) analysis using
an anti-PD-L1 antibody. We defined two cut-off points of PD-L1 expression (1 and
50%) and three corresponding IHC groups (A: 0%, B: 1-49%, and C: >=50%). IHC
group B and C were considered to be positive expression, and we defined the
difference of IHC group between pre- and post-treatment as 'major change' in PD
L1 expression. RESULTS: Before anticancer treatment, PD-L1 expression was
observed in 38/76 (50%) patients, and was significantly less common in patients
harboring mutations in the epidermal growth factor receptor gene (EGFR) than in
those without (P = 0.039). After anticancer treatment, PD-L1 expression was
observed in 36/76 (47%) patients. Major increases in PD-L1 expression were seen
in 11 (14%), and major decreases in 18 (24%) patients. Among 13 patients
harboring EGFR mutations treated with EGFR tyrosine-kinase inhibitor (EGFR-TKI),
five (38%) showed major increases. CONCLUSION: Major changes of PD-L1 expression
in tumor cells were observed in 38% of NSCLC patients who received anticancer
treatments. And, treatments with EGFR-TKI may increase PD-L1 expression in NSCLC
patients harboring EGFR mutations.
PMID- 29948242
TI - Brain imaging in pregnant women with acute headache.
AB - BACKGROUND: Brain imaging is one of the most important diagnostic methods for
evaluating headache during pregnancy. In this study, we aimed to identify
anamnestic and clinical predictors for pathological brain imaging findings in
pregnant women suffering from acute headache. METHODS: We conducted a
retrospective chart review of 151 pregnant women with acute headache between 2010
and 2016. We screened the medical records of these patients and analyzed
radiological variables, including brain imaging frequency and modality, delay to
imaging and imaging findings. In patients with brain imaging, we compared several
anamnestic and clinical features between those with and without symptomatic
pathological findings. RESULTS: Half of the patients (50.3%) underwent brain
imaging, mainly magnetic resonance imaging (MRI) including venography (53.9%) or
MRI including both venography and arteriography (31.6%). Symptomatic pathological
results could be observed in 27.6% of the patients with a brain scan. Patients in
the first trimester with acute headache had a statistically higher risk for a
symptomatic pathological imaging finding (p = 0.024). Strong pain intensity, a
reduced level of consciousness and seizures were significantly associated with a
symptomatic pathological imaging outcome across all stages of pregnancy.
CONCLUSION: Brain imaging may reveal a secondary headache etiology in more than
25% of pregnant women presenting with acute headache. In particular, when the
acute headache is of severe intensity, and the headache is accompanied by
seizures or a change in consciousness, brain imaging is required.
PMID- 29948243
TI - Transmissible amyloid protein: evidence from iatrogenic CJD.
PMID- 29948244
TI - Application value of serum biomarkers for choosing memantine therapy for moderate
AD.
AB - Although the FDA already has approved two types of drug therapies for Alzheimer's
disease, in regard to moderate AD, there is no clear research to support the best
choice of drug treatment. The goal of this study was to examine the levels of
serum biomarkers in moderate-AD patients and to explore the value of these serum
biomarkers for the diagnosis of memantine sensitivity in AD patients who are
significantly affected by MEM. In our study, 177 patients with moderate AD were
enrolled and divided into memantine-sensitive AD (n = 90) and memantine
insensitive AD (n = 87) groups. The sera from all patients were collected, and
seven serum biomarkers were analysed. Then, 120 patients were used to establish a
diagnostic model that was built with a binary logistic regression analysis, and
57 patients were used to validate our model. In addition, the area under the
receiver operating characteristic (ROC) curve was established. From the seven
serum biomarkers, the four serum biomarkers that were selected in to establish
the regression model were VEGF, BDNF, IL-6 and IL-1beta. The ROC curve of best
combined detection was 0.899. The diagnostic ratio of the logistic model was
0.825. This study suggests that the logistic regression model (LRM) and the ROC
curve based on patients' serum levels of VEGF, BDNF, IL-6 and IL-1beta is a
promising research for diagnosing and choosing the best course of treatment for
moderate AD.
PMID- 29948245
TI - Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an
Italian multicentre study.
AB - BACKGROUND: Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing
remitting multiple sclerosis (MS) in randomized clinical trials. OBJECTIVES: To
track and evaluate post-market DMF profile in real-world setting. MATERIALS AND
METHODS: Patients receiving DMF referred to Italian MS centres were enrolled and
prospectively followed, collecting demographic clinical and radiological data.
RESULTS: Among the 735 included patients, 45.4% were naive to disease-modifying
therapies, 17.8% switched to DMF because of tolerance, 27.4% switched to DMF
because of lack of efficacy, and 9.4% switched to DMF because of safety concerns.
Median DMF exposure was 17 months (0-33). DMF reduced the annual relapse rate
(ARR) by 63.2%. At 12 and 24 months, 85 and 76% of patients were relapse-free.
NEDA-3 status after 12 months of DMF treatment was maintained by 47.5% of
patients. 89 and 70% of patients at 12 and 24 months regularly continued DMF.
Most frequent adverse events (AEs) were flushing (37.2%) and gastro-enteric AEs
(31.1%). CONCLUSION: Our post-market study corroborated that DMF is a safe and
effective drug. Additionally, the study suggested that naive patients strongly
benefit from DMF and that DMF improved ARR also in patients who were horizontally
switched from injectable therapies due to tolerability and efficacy issues.
PMID- 29948246
TI - GCH1 mutations in dopa-responsive dystonia and Parkinson's disease.
AB - Guanosine triphosphate cyclohydrolase I (GCH1) mutations are associated with
increased risk for dopa-responsive dystonia (DRD) and Parkinson's disease (PD).
Herein, we investigated the frequency of GCH1 mutations and clinical symptoms in
patients with clinically diagnosed PD and DRD. We used the Sanger method to
screen entire exons in 268 patients with PD and 26 patients with DRD, with the
examinations of brain magnetic resonance imaging scans, striatal dopamine
transporter scans, and [123I] metaiodobenzylguanidine (MIBG) myocardiac
scintigraphy scans. We identified 15 patients with heterozygous GCH1 mutations
from seven probands and five sporadic cases. The prevalence of GCH1 mutations in
probands was different between PD [1.9% (5/268)] and DRD [26.9% (7/26)] (p value
< 0.0001). The onset age tends to be different between PD and DRD patients: 35.4
+/- 25.3 and 16.5 +/- 13.6, respectively (average +/- SD; p = 0.08). Most of the
patients were women (14/15). Dystonia was common symptom, and dysautonomia and
cognitive decline were uncommon in our PD and DRD. All patients presented mild
parkinsonism or dystonia with excellent response to levodopa. Seven of seven DRD
and three of five PD presented normal heart-to-mediastinum ratio on MIBG
myocardial scintigraphy. Five of six DRD and three of four PD demonstrated normal
densities of dopamine transporter. Our findings elucidated the clinical
characteristics of PD and DRD patients due to GCH1 mutations. PD patients with
GCH1 mutations also had different symptoms from those seen in typical PD. The
patients with GCH1 mutations had heterogeneous clinical symptoms.
PMID- 29948247
TI - Minocycline for acute stroke treatment: a systematic review and meta-analysis of
randomized clinical trials.
AB - BACKGROUND: Various randomized-controlled clinical trials (RCTs) have
investigated the neuroprotective role of minocycline in acute ischemic stroke
(AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate
and investigate the efficacy and safety of minocycline in patients with acute
stroke. METHODS: Literature search spanned through November 30, 2017 across major
databases to identify all RCTs that reported following efficacy outcomes among
acute stroke patients treated with minocycline vs. placebo: National Institute of
Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS)
scores. Additional safety, neuroimaging and biochemical endpoints were extracted.
We pooled mean differences (MD) and risk ratios (RR) from RCTs using random
effects models. RESULTS: We identified 7 RCTs comprising a total of 426 patients.
Of these, additional unpublished data was obtained on contacting corresponding
authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend
towards 3-month functional independence (mRS-scores of 0-2) (RR = 1.31; 95% CI
0.98-1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI - 0.92, 14.75; p = 0.08).
In AIS subgroup, minocycline was associated with higher rates of 3-month mRS
scores of 0-2 (RR = 1.59; 95% CI 1.19-2.12, p = 0.002; I2 = 58%) and 3-month BI
(MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I2 = 47%), whereas reduced the 3
month NIHSS (MD - 2.84; 95% CI - 5.55, - 0.13; p = 0.04; I2 = 86%). Minocycline
administration was not associated with an increased risk of mortality, recurrent
stroke, myocardial infarction and hemorrhagic conversion. CONCLUSIONS: Although
data is limited, minocycline demonstrated efficacy and seems a promising
neuroprotective agent in acute stroke patients, especially in AIS subgroup.
Further RCTs are needed to evaluate the efficacy and safety of minocycline among
ICH patients.
PMID- 29948248
TI - Detection of JC virus archetype in cerebrospinal fluid in a MS patient with
dimethylfumarate treatment without lymphopenia or signs of PML.
AB - We report a 76-year-old MS patient, treated with DMF for 3 years. Lymphocytes
never showed values below 1240/ul. CSF analysis revealed 1,988,880 copies/ml of
JCV-DNA, JCV-DNA was detectable in serum and anti-JCV-antibody in CSF and serum
were highly positive. Stratify(r)-JCV-test was positive. CD8-positive T
lymphocytes were reduced. Therapy with mefloquine, mirtazapine and cidofovir
resulted in complete elimination of the virus in serum and 90% reduction of viral
load in CSF. This case shows that despite careful monitoring for lymphopenia JCV
spreading to the CSF may occur during treatment with DMF.
PMID- 29948249
TI - Comparison of CT black hole sign and other CT features in predicting hematoma
expansion in patients with ICH.
AB - BACKGROUND AND PURPOSE: The hematoma expansion (HE) is an important risk factor
for early neurological deterioration and poor prognosis. In this study, we aimed
to compare the black hole sign with other computed tomography (CT) features to
predict the HE and the outcome in patients with intracerebral hemorrhage (ICH).
METHODS: Patients were enrolled within 12 h after stroke attack in the emergency
department of Henan Provincial People's Hospital between January 2012 and June
2016. The clinical characters and CT features including the initial CT and the
follow-up CT within 48 h were recorded. The outcome was assessed by using the
modified Rankin Scale on discharge. Logistic regression analyses were used to
investigate whether the factors were the independent predictor of HE and the
outcome in patients with ICH. The sensitivity, specificity, positive predictive
value, and negative predictive of CT features in predicting HE were calculated.
RESULTS: A total of 185 ICH patients were enrolled, including 70 (37.8%) patients
in HE group and 115 (62.2%) patients in non-HE group. There were significant
difference in the initial hematoma volume, irregular shape, and CT black hole
sign (P = 0.013, 0.006 and P < 0.001) between the two groups. While irregular
shape and CT black hole sign were independent predictors for HE, the sensitivity
and specificity were 71.45 and 54.78, 51.4 and 81.7%, respectively. Multivariable
analysis identified CT black hole sign (P = 0.108) and initial intraventricular
hemorrhage expansion (P = 0.214) were not the independent predictors of poor
outcome. CONCLUSION: CT black hole sign presented the best predictive accuracy of
predicting HE in patients with ICH compared to other CT features. However, it was
not an independent predictor of poor outcome.
PMID- 29948250
TI - The cognitive, affective motivational and clinical longitudinal determinants of
apathy in schizophrenia.
AB - Apathy is a frequent and debilitating condition with few treatment options
available in schizophrenia patients. Despite evidence of its multidimensional
structure, most of past studies have explored apathy through a categorical
approach. The main objective of this study was to identify the cognitive,
emotional, motivational, and clinical factors at baseline that best predicted the
three subtypes of apathy dimensions at follow-up. In a longitudinal study, 137
participants diagnosed with schizophrenia underwent different assessments
including clinical, motivational, affective and cognitive measurements, at 1
month (referred to as baseline) and 12-month follow-ups. Data were analyzed using
partial least squares variance-based structural equation modeling. Three latent
variables representing the three previously described domains of apathy reaching
consensus in the literature were extracted from the Lille Apathy Rating Scale.
Results showed that in addition to baseline apathy, positive symptoms,
anticipatory pleasure and sensibility to punishment at baseline predicted
cognitive apathy at follow-up. Likewise, both baseline apathy and sensibility to
punishment predicted emotional apathy at follow-up. Finally, baseline anhedonia
and episodic memory were the main variables the predicted behavioral apathy at
follow-up. This is the first study to show specific associations between apathy
subtypes and clinical and cognitive motivational dysfunction in individual with
schizophrenia, indicating possible distinct underlying mechanisms to these
demotivational symptoms. Treatment for apathy should address both types of
processes. Importantly, our results demonstrate the interest of multidimensional
approaches in the understanding of apathy in schizophrenia.
PMID- 29948251
TI - Biomarkers for Alzheimer's disease: from pathogenesis to drug development.
PMID- 29948252
TI - Correction to: Cingulate abnormalities in bipolar disorder relate to gender and
outcome: a region-based morphometry study.
AB - In the original publication of the article, the title was incorrect. The correct
title should read as given below.
PMID- 29948253
TI - Lifetime and 12-month prevalence estimates for mental disorders in northeastern
Germany: findings from the Study of Health in Pomerania.
AB - Few epidemiological studies presented 12-month and lifetime prevalence estimates
for DSM-IV mental disorders in the adult general population by sex and age up to
very old age. From 2007 to 2010, DSM-IV mental disorders were assessed with the
DIA-X/M-CIDI among N = 2400 participants (aged 29-89 years) from the Study of
Health in Pomerania, an epidemiological study based on a two-stage stratified
cluster sample randomly drawn from the adult general population in northeastern
Germany. 36.3% of the sample was affected by any 12-month and 54.8% by any
lifetime mental disorder. The most frequent diagnostic groups were anxiety (12
month: 14.8%, lifetime: 23.4%), substance use (12-month: 14.5%, lifetime: 25.0%),
somatoform (12-month: 12.9%, lifetime: 20.4%) and depressive (12-month: 7.3%,
lifetime: 18.6%) disorders. Except for substance use (higher prevalence in men)
and bipolar disorders (comparable prevalence in men and women), higher 12-month
and lifetime prevalence estimates were found in women vs. men. Moreover, lower 12
month and lifetime prevalence estimates were found in older (aged 60-74 or 75-89
years) vs. younger (aged 29-44 or 45-59 years) age groups. 22.6% (men: 21.1%,
women: 23.9%) of those affected by any 12-month disorder met criteria for two and
13.6% (men: 9.6%, women: 16.9%) for three or more 12-month diagnoses. Similarly,
26.4% (men: 25.7%, women: 26.9%) of those affected by any lifetime disorder met
criteria for two and 22.7% (men: 19.6%, women: 25.2%) for three or more lifetime
diagnoses. Our findings demonstrate the frequency of mental disorders in
northeastern Germany and emphasize the need for continued prevention and
intervention efforts.
PMID- 29948254
TI - Trends in paediatric inpatient antibiotic therapy in a secondary care setting.
AB - : There is growing attention for antimicrobial stewardship in paediatrics.
Currently, little is known about secondary care antibiotic practice. We analysed
trends in time with respect to inpatient antibiotic use in a secondary paediatric
care setting. Total inpatient antibiotic consumption per year (2010-2015) and
antibiotic prescriptions for urinary tract infection (UTI) and lower respiratory
tract infection (LRTI) were analysed. Variables were total, antibiotic-specific,
and intravenous days of therapy (DOT/100PD) and for UTI/LRTI treatment type,
route and duration. Third-generation cephalosporin use decreased (DOT/100PD 11.6
in 2011 vs. 5.1 in 2015; p < 0.001); intravenous antibiotics were prescribed less
often (p = 0.06). These findings were confirmed for the specific diseases: third
generation cephalosporin use decreased for both UTI (93% vs. 45%; p = 0.002) and
LRTI (14% vs. 6%; p = 0.18); the duration of intravenous therapy decreased (UTI p
= 0.02; LRTI p < 0.001). Median LRTI treatment duration was 9.2 days in 2008 and
6.6 in 2015 (p < 0.001); penicillin prescriptions were more narrow in spectrum (p
= 0.02). CONCLUSION: A decrease in third-generation cephalosporin use and
intravenous route was identified. LRTI treatment was significantly shorter and
more narrow in spectrum. This could be explained by awareness and interventions
in the context of antimicrobial stewardship. A decrease in antibiotic use is also
feasible and important in non-tertiary paediatric wards. What is Known: *
Antimicrobial stewardship programmes are effective in reduction of total and
broad-spectrum antibiotic use in tertiary paediatric hospitals * The majority of
hospitalised paediatric patients are admitted at general, secondary care wards,
often for infectious diseases What is New: * Antimicrobial stewardship
interventions in secondary care are also effective in establishing a reduction in
broad-spectrum antibiotic use, intravenous route and days on antibiotic therapy.
PMID- 29948255
TI - Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children:
a meta-analysis of 4442 cases.
AB - : The purpose of this study was to identify the clinical features and laboratory
factors that are predictive of intravenous immunoglobulin (IVIG)-resistant
Kawasaki disease. Multiple databases were searched for relevant studies on IVIG
resistant Kawasaki disease published from January 2002 to April 2017. Eligible
studies were retrieved by manual review of the references. Stata 12 was used for
the meta-analysis. Weighted mean differences and odds ratios with 95% confidence
intervals were calculated for several indices. Twenty-eight studies involving
26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and
21,818 IVIG-sensitive Kawasaki disease patients were included. The meta-analysis
showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group
was significantly higher than that in the IVIG-sensitive group, and that platelet
count and hemoglobin levels were significantly lower in the IVIG-resistant group.
The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of
the extremities, polymorphous rash, and initial administration of IVIG <= 4.0
days after the onset of symptoms were more likely to be IVIG resistant.
CONCLUSION: The initial administration of IVIG <= 4.0 days after the onset of
symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa
alterations, cervical lymphadenopathy, swelling of the extremities, and
polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease.
What is Known: * Recent reports on this topic are about aspartate
aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl
transferase, total bilirubin, white blood cells, platelets, erythrocyte
sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein
(CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk
factors in the IVIG-resistant Kawasaki disease; however, no studies have been
published on clinical features as predictors of IVIG resistance. What is New: *
This meta-analysis identified the clinical features, the initial administration
of IVIG <= 4.0 days after the onset of symptoms, and much more comprehensive
laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant
Kawasaki disease.
PMID- 29948256
TI - Ocular findings in Noonan syndrome: a retrospective cohort study of 105 patients.
AB - : The aim of this retrospective study is to describe ocular findings in a large
Noonan syndrome cohort and to detect associations between ocular features and
genetic mutations that were not found in earlier studies. We collected
ophthalmological and genetic data of 105 patients (median age, 12 years; range, 0
60 years) clinically diagnosed as Noonan syndrome. The ocular findings were
linked to the genotypes. All patients with Noonan syndrome showed multiple
abnormalities in the categories of vision and refraction, external ocular
features, ocular alignment and motility, anterior ocular segment, and posterior
ocular segment. In total, 50 patients have NS due to a mutation in PTPN11.
Permanent visual impairment (bilateral best-corrected visual acuity < 0.3) was
found in 7 patients, including patients with a mutation in RAF1, SHOC2, and KRAS.
Keratoconus was found in 2 PTPN11 positive patients, and prominent corneal nerves
were observed in a patient with a SOS1 mutation. CONCLUSIONS: This study shows an
overview of ocular abnormalities in Noonan syndrome, including permanent visual
impairment caused by binocular optic nerve abnormalities and nystagmus. Delay in
ophthalmological diagnosis is still present, also in patients with visual
impairment. All Noonan syndrome patients should have a complete ophthalmological
examination at the time of diagnosis. What is Known: * Although we discover more
pathogenic mutations in patients with Noonan syndrome, Noonan syndrome still is a
clinical diagnosis * Ocular features of Noonan syndrome are characterized by
developmental anomalies of the eyelids and associated with other ocular
abnormalities in childhood (including refractive errors, strabismus and
amblyopia). What is New: * There seems to be a delay in the ophthalmological
diagnosis and awareness of the broad variety ofophthalmological features
including refractive errors and visual impairment in Noonan syndrome is needed.
All children should have a full ophthalmological examination at the time of
diagnosis. * Permanent visual impairment (best-corrected visual acuity < 0.3) is
found in patients with mutations in RAF1, SHOC2, and KRAS and the cause is
probably a developmental disorder of the optic nerves.
PMID- 29948257
TI - Response to "Bacteria from bronchoalveolar lavage fluid from children with
suspected chronic lower respiratory tract infection: results from a multi-center,
cross-sectional study in Spain" Eur J Pediatr (2018) 177:181-192.
PMID- 29948259
TI - Swallowing Changes in Community-Dwelling Older Adults.
AB - Older adults may evidence changes in swallowing physiology. Our goals were to
identify dysphagia risk in community-dwelling older adults with no history of
dysphagia, and to compare swallowing physiology and safety between older and
younger adults. Thirty-two older adults with no history of dysphagia were
prospectively recruited and completed the Dysphagia Handicap Index (DHI), two
trials of a 3 oz. swallow screen, and videofluoroscopy (VFSS). Self-ratings of
swallowing function were compared to published norms by paired t tests, and
multivariate logistic regression models were generated to determine whether these
ratings and VFSS analysis of swallowing function were associated with failure of
one or both swallow screen trials. Archived VFSS of 33 younger adults were
compared to older adults with Wilcoxon rank-sum tests. The DHI scores of older
adults were higher than published non-dysphagic adults but lower than dysphagic
adults. Older participants with greater Oral Residue scores were more likely to
fail both swallow screen trials. Older adults received higher median MBSImPTM(c)
scores for select pharyngeal components than younger adults. The two age groups
did not differ on Penetration-Aspiration Scale scores, and no aspiration was
observed. Measures of swallowing in older individuals may reflect age-related
sensory and motor changes in the context of functional swallowing and adequate
airway protection.
PMID- 29948258
TI - Authors' response to correspondence for EPI-STREP-064 publication.
PMID- 29948260
TI - Predictors of Patient-Reported Dysphagia Following IMRT Plus Chemotherapy in
Oropharyngeal Cancer.
AB - The aim of this cross-sectional study is to evaluate the factors associated with
patient-reported dysphagia in patients affected by locally advanced oropharyngeal
cancer (OPC) treated with definitive intensity-modulated radiation therapy (IMRT)
and concurrent chemotherapy (CHT), with or without induction CHT. We evaluated
148 OPC patients treated with IMRT and concurrent CHT, without evidence of
disease and who had completed their treatment since at least 6 months. At their
planned follow-up visit, patients underwent clinical evaluation and completed the
M.D. Anderson dysphagia inventory (MDADI) questionnaire. The association between
questionnaire composite score (MDADI-CS) and different patients' and tumor's
characteristics and treatments (covariates) was investigated by univariable and
multivariable analyses, the latter including only covariates significant at
univariable analysis. With a median time from treatment end of 30 months [range 6
74 months, interquartile range (IQR) 16-50 months], the median (IQR) MDADI-CS was
72 (63-84). The majority of patients (82.4%) had a MDADI-CS >= 60. At
multivariable analysis, female gender, human papilloma virus (HPV)-negative
status, and moderate and severe clinician-rated xerostomia were significantly
associated with lower MDADI-CS. Patient-perceived dysphagia was satisfactory or
acceptable in the majority of patients. HPV status and xerostomia were confirmed
as important predictive factors for swallowing dysfunction after
radiochemotherapy. Data regarding female gender are new and deserve further
investigation.
PMID- 29948261
TI - Tongue Pressure Measurement and Videofluoroscopic Study of Swallowing in Patients
with Parkinson's Disease.
AB - This study investigated the relationship between tongue pressure during
swallowing and dysphagia in patients with Parkinson's disease (PD). A total of 24
patients with PD (12 men and 12 women, mean age 70.4 years) were studied. Their
mean Hoehn and Yahr scale was 3.0 +/- 1.3 (range 1-5). All participants underwent
tongue pressure measurement and videofluorography during swallowing. Tongue
pressure when swallowing 5 mL of barium on videofluorography was measured using a
sensor sheet with five sensors. Based on the findings of videofluorography, the
patients were divided into two groups: dysphagic PD group (n = 9) and non
dysphagic PD group (n = 15). The maximal magnitude (kPa), duration (s), time to
peak pressure (s), and pressure gradient (kPa/s) of tongue pressure were analyzed
for each part. For duration, time to peak pressure, and pressure gradient,
similar values were calculated from the total waveform. There was no significant
difference in maximal tongue pressure between the groups. The dysphagic PD group
had prolonged duration of tongue pressure and time to peak pressure and a reduced
pressure gradient compared with the non-dysphagic PD group. These results
indicate that there is a clear difference in the temporal aspects of tongue
pressure between the non-dysphagic and dysphagic PD patients. These differences
provide the characteristics of tongue movement during swallowing in PD patients
with dysphagia, which may be useful for the diagnosis and treatment of dysphagia.
PMID- 29948262
TI - Characterizing the Flow of Thickened Barium and Non-barium Liquid Recipes Using
the IDDSI Flow Test.
AB - The use of thickened liquids for dysphagia management has become wide-spread.
Videofluoroscopy is commonly used to determine dysphagia severity and to evaluate
the effectiveness of interventions, including texture modification, but this
requires the use of radio-opaque contrast media. In order for the results of a
videofluoroscopy to have validity with respect to confirming swallowing safety
and efficiency on different liquid consistencies, it is important to understand
the flow characteristics of the contrast media used and how the flow of these
stimuli compares to the flow of liquids that are provided outside the assessment
context. In this study, we explored the flow characteristics of 20% w/v barium
and non-barium stimuli prepared using starch and gum thickeners to reach the
slightly, mildly and moderately thick liquid categories defined by the
International Dysphagia Diet Standardisation Initiative (IDDSI). Our goal was to
identify recipes that would produce stimuli with stable flow properties over a 3
h time frame post mixing. Thickener concentration was titrated to achieve
matching flow (i.e., IDDSI Flow Test results within a 1 ml range) across the four
stimulus types (non-barium starch, non-barium gum, barium starch, barium gum)
within each IDDSI level. The combination of barium and thickeners resulted in
further thickening, particularly with starch-based thickening agents. A probe of
the influence of refrigeration showed no difference in flow measures between
chilled and room temperature stimuli over a 3-h time frame. Overall, recipes with
stable flow over three hours were identified for all barium and non-barium
liquids tested.
PMID- 29948263
TI - IgG4-related disease: association between chronic rhino-sinusitis and systemic
symptoms.
AB - PURPOSE: The objective of this study is to analyze the relationship between
chronic rhino-sinusitis (CRS) and systemic symptoms in patients with IgG4-related
disease (IgG4-RD). PATIENTS AND METHODS: The patients with IgG4-RD, confirmed by
restrict association with clinical and histopathological manifestations between
March 2013 and July 2016, were enrolled and followed-up for 1 year at the Tongren
Hospital, Capital Medical University. The patients were divided into two groups:
the case group included IgG4-RD patients with CRS confirmed by clinical and
imaging, while the control group included IgG4-RD patients without CRS confirmed
by clinical and imaging. Age, gender, clinical manifestations, the percentage of
eosinophils in peripheral blood, sedimentation (ESR), C-reaction protein, serum
IgE and IgG4 levels, histopathology, and treatment drugs at the baseline and 1
year of follow-up were compared between the two groups. RESULTS: A total of 46
cases met the diagnostic criteria for IgG4-RD. A total of 30 patients (65.2%) had
IgG4-RD complicated with CRS, and were aged 49.7 +/- 13.4 years, with male:female
ratio = 2:1. The disease duration in the case group was longer than that in the
control group (3.0 versus 0.8, p = 0.009). The ratio of ocular involvement was
higher (86.7 versus 60%, p < 0.001), and allergic manifestations including drug
allergy, asthma, and allergic skin were more common (56.5 versus 20%, p = 0.004),
with a higher percentage of eosinophils in peripheral blood (8.5 versus 3.3%, p =
0.018) and more sensitive to glucocorticoids (6.0 versus 3.5, p = 0.004) than
those in the control group. CONCLUSIONS: CRS in patients with IgG4-RD was closely
associated with IgG4-related ocular lesions, which was more prone to allergic
manifestations accompanied by raised percentage of eosinophils in peripheral
blood. The treatment of patients with IgG4-RD complicated with CRS was more
effective than those with IgG4-RD without CRS.
PMID- 29948264
TI - Otogenic lateral sinus thrombosis in children: proposal of an experience-based
treatment flowchart.
AB - PURPOSE: To describe the prevalent clinical, laboratory, and radiological
features of otogenic lateral sinus thrombosis (OLST) in children; to identify
clinical predictors of outcome; to propose a management algorithm derived from
experience. METHODS: A retrospective review was conducted of the clinical records
of patients with OLST, treated in a single tertiary care referral center for
pediatric disease from 2006 to 2017. The inclusion criteria were pediatric age (0
16 years) and OLST diagnosis confirmed by a pre- and post-contrast CT or
venography-MRI scan. Primary outcome measures were early (1-2 months) and late (6
months) sinus recanalization assessed by means of neuroimaging. RESULTS: Twenty
five patients (8 females and 17 males; mean age = 6 +/- 3 years) were included. A
genetic abnormality associated with thrombophilia was found in 24 (96%) patients.
At diagnosis, anticoagulant treatment with low-molecular-weight heparin (LMWH)
was started in all subjects, while surgical treatment (mastoidectomy and
tympanostomy tube insertion) was performed in 16/25 (64%) patients. Follow-up
neuroimaging showed lateral sinus recanalization in 12/25 (48%) patients after 1
2 months and in 17/25 (68%) after 6 months. At multivariate logistic regression
analysis, no significant predictors of the early and late neuroradiological
outcome were found. CONCLUSIONS: All children with OLST should be screened for
thrombophilia to decide on treatment duration and to assess the need for future
antithrombotic prophylaxis. Immediately after diagnosis, anticoagulant treatment
with LMWH should be started according to the international guidelines. Instead,
our experience suggests that surgical treatment should not be indicated in all
patients, but decided on a case-to-case basis.
PMID- 29948265
TI - Length of the ossified stylohyoid complex and Eagle syndrome.
AB - PURPOSE: To assess radiographically the presence of an ossified stylohyoid
complex (OSHC) with signs and symptoms of Eagle syndrome or other oro-facial
painful diseases in patients attending our institution and to confirm that the
important issue for study is to know the length of the ossificated portion of the
stylohyoid complex only. METHODS: We separated 1000 consecutive files, and after
selection, 922 panoramic radiographs were evaluated. Assessed parameters were
gender and age of the patients, size, and location of the analyzed OSHCs. In
addition, the length parameters of the studied OSHCs were also determined in 100
extra radiographs. RESULTS: Normal length of OSHCs was between 2.83 and 4.16 cm
and OSHCs measuring more than 4.17 cm long comprising 23.2% of the sample. Any of
the patients with OSHC presented signs or symptoms of the Eagle syndrome or any
other orofacial painful disease. CONCLUSIONS: This is the first study on OSHCs
using the mandatory parameters of normal, short and elongated length in the
studied population. Our results suggest that the presence of an OSHC is not an
important feature for pain detection in the Eagle syndrome and is not an
important risk factor for development of throat pain in this and other painful
orofacial diseases. Our results are different from those previously published in
other populations and suggest that the widely used lengths of 2 to 4 cm for
measuring the OSHCs are not adequate parameter. It is desirable to define first
the short, normal and abnormal parameters of OSHCs in each studied population.
PMID- 29948266
TI - Polypoid change of middle turbinate is associated to an increased risk of polyp
recurrence after surgery in patients with chronic rhinosinusitis with nasal
polyps.
AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) affects
approximately 4% of general population. Patients with CRSwNP have greater burden
of CRS symptoms and higher rate of relapse after either medical or surgical
treatments. The aim of this study was to evaluate the association between
polypoid change of anterior free border of middle turbinate and rate of relapse
in patients with CRSwNP. METHODS: A controlled prospective cohort study was
performed. Seventy-seven adult patients with CRSwNP in whom their MT polypoid
change was proved and 77 patients without MT polypoid change were recruited.
Allergy, asthma, aspirin hypersensitivity, Lund Kennedy and Lund Mackay scores
and eosinophilic scores of polyp and middle turbinate were recorded. Patient's
health-related quality of life was assessed using the 22-item Sino-Nasal Outcome
Test (SNOT-22) questionnaire. All patients were evaluated 12 months after ESS.
Polyp relapse, Lund Kennedy scores and SNOT-22 scores were documented. RESULTS:
The relapse rate in patients with MT polypoid change was significantly higher
than the control group (37.14 vs. 20.58, p value = 0.03). Eosinophil score of
nasal polyps and MT specimens were significantly higher in patients with MT
polypoid change than patients without polypoid change. The postoperative Lund
Kennedy and SNOT-22 scores in patients with MT polypoid change were significantly
higher than the control group. CONCLUSION: This study showed a significant
association between polypoid change of anterior free border of middle turbinate
and nasal polyp relapse. This new and simple criterion of severity of CRSwNP
could have clinical implications.
PMID- 29948267
TI - Factors contributing to surgical site infection in patients with oral cancer
undergoing microvascular free flap reconstruction.
AB - PURPOSE: Surgical site infections (SSIs) are associated with considerable medical
expenditure. While head and neck free flap reconstruction has gradually become
routine management following an ablative oncologic resection, reports on factors
contributing to the SSIs are lacking. METHODS: We retrospectively analyzed 173
new patients with oral cancer without any antecedent treatment at a tertiary
medical center from 2010 to 2015. We determined incidence rates of SSIs within 30
days postoperatively and identified independent risk factors using multivariate
logistic regression analysis. RESULTS: Of 173 patients, 67 (38.7%) had SSIs.
Multivariate analysis demonstrated operative time [odds ratio (OR) = 1.199, 95%
confidence interval (CI) = 1.036-1.389], mandibulectomy (OR = 2.759; 95% CI =
1.245-6.111), and oro-neck communication (OR = 5.358; 95% CI = 2.150-13.355) as
independent predictors for SSIs. CONCLUSIONS: For patients with oral cancer
undergoing free tissue reconstruction, mandibulectomy, oro-neck communication,
and prolonged operative time were associated with increased incidence of SSIs.
PMID- 29948268
TI - Role of asthma and intolerance to acetylsalicylic acid on the redox profile in
nasal polyp tissue.
AB - PURPOSE: Nasal polyposis is a chronic inflammatory disease of the mucosa of the
nasal cavity and paranasal sinuses. The etiology of nasal polyposis is unclear;
however, it may be associated with asthma and intolerance to acetylsalicylic
acid, possibly altering the redox profile. The study intends to compare the redox
profile in polyps surgically removed from three clinical groups of patients with
nasal polyposis who were divided according to the presence of asthma and
intolerance to acetylsalicylic acid. METHODS: Patients were divided into three
groups: nasal polyposis only (n = 30); nasal polyposis and asthma (n = 19); and
nasal polyposis, asthma and intolerance to acetylsalicylic acid (n = 10). The
following redox evaluations were performed: enzymatic antioxidant activity of
superoxide dismutase, glutathione peroxidase, hydrogen peroxide consumption and
glutathione S-transferase; non-enzymatic antioxidant levels of vitamin C, vitamin
E and glutathione; levels of the oxidative damage biomarkers carbonyl groups
(measuring protein damage) and malondialdehyde (measuring lipid peroxidation);
and nitrite and nitrate levels. RESULTS: Compared with the polyposis only group,
hydrogen peroxide consumption, glutathione S-transferase, vitamin E and
malondialdehyde were lower in the asthma group. Total glutathione (0.12 +/- 0.01
vs. 33.34 +/- 10.48 umol/mg) and nitrite and nitrate (0.06 +/- 0.01 vs. 15.95 +/-
1.38 nmol/mg) levels were higher in the nasal polyposis, asthma and intolerance
to acetylsalicylic acid group. CONCLUSIONS: In patients with nasal polyposis,
asthma may alter the redox profile associated with the hydrogen peroxide and
lipid damage pathways, whereas asthma and intolerance to acetylsalicylic acid
increase nitrite and nitrate and total glutathione levels.
PMID- 29948270
TI - Acoustic neuroma quality of life: are we missing the point?
PMID- 29948269
TI - Subjective effects of the sleep position trainer on snoring outcomes in position
dependent non-apneic snorers.
AB - PURPOSE: To evaluate the effect of a new-generation positional device, the sleep
position trainer (SPT), in non-apneic position-dependent snorers. METHODS: Non
apneic position-dependent snorers with an apnea-hypopnea index (AHI) < 5 events/h
were included between February 2015 and September 2016. After inclusion, study
subjects used the SPT at home for 6 weeks. The Snore Outcome Survey (SOS) was
filled out by the subjects at baseline and after 6 weeks, and at the same time,
the Spouse/Bed Partner Survey (SBPS) was filled out by their bed partners.
RESULTS: A total of 36 participants were included and 30 completed the study. SOS
score improved significantly after 6 weeks from 35.0 +/- 13.5 to 55.3 +/- 18.6, p
< 0.001. SBPS score also improved significantly after 6 weeks from 24.7 +/- 16.0
versus 54.5 +/- 25.2, p < 0.001. The severity of snoring assessed with a numeric
visual analogue scale (VAS) by the bed partner decreased significantly from a
median of 8.0 with an interquartile range (IQR) of [7.0-8.5] to 7.0 [3.8-8.0]
after 6 weeks (p = 0.004). CONCLUSIONS: Results of this study indicate that
positional therapy with the SPT improved several snoring-related outcome measures
in non-apneic position-dependent snorers. The results of this non-controlled
study demonstrate that this SPT could be considered as an alternative therapeutic
option to improve sleep-related health status of snorers and their bed partners.
PMID- 29948271
TI - Long-term follow-up of inactive occlusal caries lesions: 4-5-year results.
AB - OBJECTIVE: To assess the clinical behavior of inactive caries lesion on the
occlusal sites of permanent molars over 4-5 years and to estimate the risk for
progression of caries-inactive sites compared with sound ones. METHODS: Clinical
examinations were conducted at baseline (n = 258) and after 4-5 years and
included the recording of dental plaque and dental caries at the occlusal
surfaces and the eruption stage of each permanent molar. RESULTS: One hudred
ninety-three schoolchildren were followed (response rate of 74.8%), totalizing
1152 teeth. Of the children, 30.6% (n = 59) presented at least one molar
containing an active lesion, filling, or that had been extracted; according to
the activity criterion, inactive lesions presented around a twofold increased
risk for caries progression than sound surfaces (OR = 2.34 95%CI = 1.51-3.62).
Thirteen percent (n = 25) of the children presented at least one molar
progressing to dentine cavity, filling, or extraction; according to the severity
criterion, inactive caries lesions presented a significantly higher risk for
progression when compared with sound surfaces (OR = 2.69, 95% CI = 1.50-4.83).
CONCLUSION: The vast majority of lesions (85-90%) identified as inactive enamel
caries at baseline did not progress over 4-5 years. Despite this fact, it was
possible to detect an increased risk for caries progression in caries-inactive
occlusal sites compared with the sound ones. CLINICAL RELEVANCE: Considering the
low progression rates, inactive caries lesions do not need a specific caries
controlling treatment and should be monitored longitudinally in the same manner
as sound surfaces.
PMID- 29948272
TI - Remineralization capacity of carious and non-carious white spot lesions: clinical
evaluation using ICDAS and SS-OCT.
AB - OBJECTIVES: To assess the remineralization capacity of carious, non-carious, and
combined white spot lesions (WSLs) using the ICDAS and SS-OCT. MATERIALS AND
METHODS: This clinical trial was based on a quasi-experimental design. Forty-two
healthy subjects (median age 26.6 years), who visited university hospital and had
at least one WSL with an ICDAS score of 2 or 1, were recruited. The subjects
chewed a non-blind sugar-free gum containing bioavailable calcium and fluoride
for 3 months. The remineralization capacities of carious and non-carious 121 WSLs
were assessed using ICDAS by two calibrated non-blind examiners and optical
boundary depth (BD) by SS-OCT at a monthly recall. The outcome variables,
transitions of ICDAS score, mean BD, and mean BD recovery rate (RR%), were
statistically analyzed using the chi-square test, two way-repeated measures
ANOVA, and Wilcoxon rank sum test, respectively (alpha = 0.05). RESULTS: Based on
the visual inspection, OCT images at the baseline, 72 WSLs were purely carious,
20 were non-carious (developmental) lesions, while 29 were combined (carious
developmental). The responses of WSLs over time showed to be highly variable.
There was a significant difference in transitions of ICDAS scores after 3 months
between carious and non-carious WSLs (p < 0.05) and non-carious and combined WSLs
(p < 0.05). Carious and combined WSLs underwent significant changes in the mean
BD between baseline (161.8 +/- 56.8 MUm) and 2 months (130.7 +/- 57.4 MUm) or 3
months (119.1 +/- 57.5 MUm) (p < 0.05), while there was no significant difference
between baseline (132.2 +/- 26.2 MUm) and 2 months (122.8 +/- 24.1 MUm) or 3
months (119.8 +/- 22.6 MUm) in non-carious WSLs (p > 0.05). There was a
significant difference in mean RR% after 2 and 3 months between carious and non
carious WSLs (p < 0.05). CONCLUSIONS: The remineralization capacity of WSL was
variable among the cases and subjects, and depended on the WSLs history, etiology
(carious, non-carious, or combined lesion) and structure (histological pattern).
CLINICAL RELEVANCE: Carious WSLs showed the highest remineralization potential.
PMID- 29948273
TI - The impact of premature birth on dental maturation in the permanent dentition.
AB - OBJECTIVES: To evaluate tooth development and calculate dental maturity score in
prematurely born children and to compare the findings with full-term born
children. MATERIAL AND METHODS: Nine-year-old preterm children were selected from
the Swedish Medical Birth Register. One group consisted of 36 extremely preterm
children (born before week 29), and the other included 38 very preterm children
(born during weeks 29 to 32). Panoramic radiography was performed on each child
and the preterm children were compared with 42 full-term born children. Five
observers independently assessed the tooth development stages for all teeth in
the left mandible (31-37) on the panoramic radiographs according to the method
described by Demirjian et al. (Hum Biol 45:211-227, 1973). Data from tooth
development stages were compiled and converted into a dental maturity score for
each group. Kappa values were calculated for intra- and inter-observer agreement.
RESULTS: When the different development stages for each individual tooth were
compared, all observers presented a significant delay in the maturity of tooth 37
for the extremely preterm group (p <= 0.002). The extremely preterm group had a
significantly lower dental maturity score than the full-term group, as assessed
by each observer (p <= 0.006). Kappa values for inter-observer agreement varied
between 0.31 and 0.71 depending on tooth and intra-observer agreement was between
0.16 and 1.0. CONCLUSIONS: At age 9, the extremely preterm children had a general
delay in tooth development. CLINICAL RELEVANCE: The increased survival rate of
extremely preterm babies adds a new group of children to society. Dental
clinicians should be aware that the delay in tooth development could impact the
timing of orthodontic diagnostics and potential treatment.
PMID- 29948274
TI - Validity of Chronic Oral Mucosal Diseases Questionnaire in oral submucous
fibrosis.
AB - OBJECTIVE: To validate the use of Chronic Oral Mucosal Diseases Questionnaire in
oral submucous fibrosis. MATERIALS AND METHODS: Hundred consecutive oral
submucous fibrosis (OSF) patients were requested to respond to Visual Analogue
Scale (VAS) score and complete the Oral Health Impact Profile 14 (OHIP 14) and
COMDQ. Spearman's rho correlation was used to assess the relationship between VAS
and COMDQ score and COMDQ and OHIP 14 score. The reliability of the instrument
was assessed using Cronbach's alpha analysis. Discriminant analysis was used to
assess if COMDQ significantly differentiated between OSF population with and
without any prior treatment done as well as OSF with mouth opening less than and
more than or equal to 25 mm. RESULTS: The Spearman's correlation coefficient
showed a high significance between the different domains of COMDQ and OHIP 14 and
COMDQ and VAS. This study demonstrated a good convergent validity between the
overall COMDQ and OHIP 14 scores (0.88).The overall Cronbach's alpha value was
found to be 0.75 indicating an acceptable internal consistency reliability of
COMDQ. The tool was unable to differentiate between patients with mouth opening
between less than and more than or equal to 25 mm and patients with and without
prior treatment. CONCLUSION: These results provide evidence that COMDQ can be
used for OSF patients. CLINICAL RELEVANCE: COMDQ could be used as a valid and
reliable tool for further clinical OSF research.
PMID- 29948275
TI - One-year clinical evaluation of bulk-fill flowable vs. regular nanofilled
composite in non-carious cervical lesions.
AB - OBJECTIVE: The aim of this double-blind, randomized trial was to evaluate the 1
year clinical performance of a bulk-fill flowable and a regular nanofilled
composite in non-carious cervical lesions (NCCLs). METHODS: Twenty-two subjects
with at least two NCCLs were enrolled in the study. A total of 89 restorations
were performed by a single operator using Filtek Supreme (FS) Ultra Universal or
Filtek Bulk (FB) Fill Flowable. A universal adhesive (ScotchbondTM Universal
Adhesive) was used with a self-etching approach in dentin. The restorations were
evaluated by two independent and previously calibrated examiners at baseline (7
days), 6 months and 1 year, according to the USPHS modified criteria. Mann
Whitney U test was used to analyze the differences between composites and
Wilcoxon signed rank test for comparisons between the baseline and follow-ups
(alpha = 5%). RESULTS: One restoration was considered clinically unacceptable due
to loss of retention after 6 months in the FS group. FS presented statistically
high scores for surface roughness when compared to FB after 1 year (p < 0.05),
but both were considered clinically acceptable. After 1 year, the frequency of
clinically unacceptable rates was 3.3% for anatomical form in the FB group, 1.1%
for retention in the FS group, and 2.2% for marginal adaptation in both groups.
All restorations, in both groups, presented score 0 over the 1-year period for
marginal staining, postoperative sensitivity, and secondary caries. CONCLUSION:
Both composite resins showed acceptable clinical performances for the restoration
of NCCLs after 1 year. CLINICAL RELEVANCE: Both bulk-fill flowable and regular
nanofilled composites showed good clinical performances for the restoration of
NCCLs after 1 year.
PMID- 29948276
TI - Does enamel matrix derivative application improve clinical outcomes after
semilunar flap surgery? A randomized clinical trial.
AB - OBJECTIVES: To evaluate the treatment of gingival recessions by semilunar
coronally positioned flap plus enamel matrix derivative (SCPF + EMD). MATERIALS
AND METHODS: Thirty patients with class I localized gingival recession were
included. They were randomly allocated in two groups: SCPF + EMD and SCPF.
Recession height (RH), recession width (RW), width of keratinized tissue (WKT),
thickness of keratinized tissue (TKT), probing depth (PD), and clinical
attachment level (CAL) were measured at baseline, 6 and 12 months post-surgery.
Patient/professional evaluation of esthetics and root sensitivity was performed.
RESULTS: After 12 months, mean root coverage was 1.98 +/- 0.33 mm for SCPF + EMD
(90.86 +/- 14.69%) and 1.85 +/- 0.41 mm (79.76 +/- 17.44%) for SCPF (p > 0.05).
The esthetic evaluation by the patient showed preference for SCPF + EMD.
According to the professional evaluation (QCE), the use of EMD decreases the
appearance of postoperative scar tissue line. There was a significant reduction
in root hypersensitivity with no further complaints by the patients. CONCLUSIONS:
The addition of EMD provides significantly better esthetics to SCPF, according to
patient and professional assessments. SCPF + EMD is effective but not superior to
SCPF for root coverage, after 12 months. CLINICAL RELEVANCE: Previous clinical
trials showed that the combination of EMD with coronally advanced flaps may
enhance the outcome of root coverage. There is a lack of studies testing the
combination of EMD with SCPF. The combination SCPF + EMD provides better
esthetics when compared to the SCPF and is effective, but not superior, to SCPF
for root coverage, after 12 months. TRIAL REGISTRATION: NCT02459704.
PMID- 29948278
TI - Induced surface proteins of Streptococcus epidermidis adhering to titanium
implant substrata.
AB - OBJECTIVE: Staphylococcus epidermidis, as a primary colonizer, is strongly
associated with infections of (dental) implants (i.e., peri-implantitis), but
little is known about the surface proteome of this bacterium. For the
identification of bacterial adhesins, this study investigated the surface
proteome of S. epidermidis adhering directly to titanium implant substrata.
MATERIALS AND METHODS: S. epidermidis strain ATTC 35984 was cultured either
planktonically or on titanium implant specimens. The surface proteomes were
isolated by mutanolysin digestion, and proteins were separated by 2D gel
electrophoreses to reveal highly expressed proteins only. Protein spots were
visualized by silver staining and proteins were identified by mass spectrometry.
RESULTS: Surface proteome analyses of S. epidermidis on titanium identified six
expressed proteins. Three proteins were highly expressed on the titanium implants
including accumulation-associated protein Q8CQD9. These specific proteins could
be potential pathogenicity factors of bacteria in peri-implant biofilms.
CONCLUSION: For the first time, our study identified S. epidermidis surface
proteins, which are expressed after adhesion to titanium implant materials.
CLINICAL RELEVANCE: Our study reveals possible candidates for a newly protein
based vaccine against peri-implantitis.
PMID- 29948277
TI - Locally applied statins as adjuvants to non-surgical periodontal treatment for
chronic periodontitis: a systematic review and meta-analysis.
AB - OBJECTIVE: This review aimed at evaluating the effects of chronic periodontitis
(CP) treatment with local statins as adjuncts to scaling and root planing (SRP),
compared with SRP alone or with placebo. METHODS: Electronic and hand searches
were conducted in three databases to select randomized controlled trials (RCTs)
comparing SRP + statins versus SRP alone. Random effects models were conducted to
determine the clinical attachment level (CAL) gain as the primary outcome
variable, and probing pocket depth (PPD) reduction, modified sulcus bleeding
index (mSBI), and intrabony defect depth (IBD) as the secondary outcomes.
RESULTS: Of the 526 papers identified, 15 articles met the criteria for inclusion
in this systematic review, and 13 in the meta-analysis. The meta-analysis showed
a statistically significant CAL gain (mean differences [MD] = 1.84 mm, 95%
confidence interval [CI] = 1.45 to 2.23; p = 0.000), PPD reduction (MD = 1.69 mm,
95% CI = 1.37 to 2.04; p = 0.000), mSBI change (MD = 0.70, 95% CI = 0.57 to 0.84;
p = 0.000), and IBD (MD = 1.48, 95% CI = 1.30 to 1.67; p = 0.000) attributed to
SRP + statin treatment (6 months). CONCLUSION: Within the limitations of this
study, the collective evidence emerging from this systematic review and meta
analysis may support the use of locally applied statins as adjuncts to SRP in CP
treatment, based on being an easy, low-cost alternative, with lesser adverse
effects on bacterial resistance. These results should be interpreted with
caution. CLINICAL RELEVANCE: Clinicians might consider the use of SRP + statins
as an adjunct over other alternative approaches, based on the results of the
present review. The informed decision should be taken, considering the patient's
values and preferences, and the intervention to be implemented by the clinician.
PMID- 29948279
TI - Effects of two disinfection/sterilization methods for dentin specimens on dentin
permeability.
AB - OBJECTIVES: To investigate the effects of two disinfection/sterilization methods
on the permeability of dentin specimens. MATERIALS AND METHODS: Forty intact
human third molars were freshly extracted and cut, close to the pulp chamber,
into dentin disks with a 500-MUm thickness. The disks were randomized (n = 20
each) into a 70% ethanol group (acid-etched dentin disks soaked in 70% ethanol
for 15 min) and a steam autoclaving group (acid-etched dentin disks autoclaved
for 25 min). The permeability (Lp) of each dentin disk was measured before and
after either treatment using a hydraulic device, and intra- and inter-group
differences in values before and after treatment were analyzed using t tests.
Field emission scanning electron microscopy (FE-SEM) micrographs of the dentin
surface were acquired and examined. FE-SEM samples were prepared using the
critical point drying (CPD) method. RESULTS: Immersion in 70% ethanol increased
the Lp values of dentin specimens by 17%, which was not statistically
significant. Steam autoclaving significantly reduced dentin permeability by 66%
because the dentin collagen mesh became compact and collapsed, as detected by FE
SEM. CONCLUSIONS: The disinfection of acid-etched dentin disks using 70% ethanol
for 15 min does not significantly affect dentin permeability, whereas
sterilization of acid-etched dentin disks via autoclaving significantly reduces
dentin permeability. CLINICAL RELEVANCE: Considering the influences of dentin
permeability by disinfection/sterilization methods, the disinfection of the acid
etched dentin disks using 70% ethanol for 15 min could be used for the study
related to dentin permeability, while the sterilization of autoclaving could not.
PMID- 29948280
TI - Evaluation of risk factors for oral infection with potential for spread in a 1
year cohort study.
AB - OBJECTIVES: To determine the frequency of oral infection with potential for
spread (OIPS) and behavioural risk factors in patients referred to a regional
tertiary care-centre for OIPS assessment and clearance. MATERIALS AND METHODS: A
database search of all referrals to the Oral and Maxillofacial Diseases unit of
HUH in 2009 was performed. Of the 2807 referrals, 408 were due to a known or
suspected OIPS. The electronic patient records of these patients were analysed
for patient demographics, lifestyle factors, radiological findings and clinical
oral findings. Risk factors for OIPS were analysed using logistic regression and
using the significant factors in univariate analyses in the multivariate models.
RESULTS: The mean age of the patients was 58 years. Most patients (n = 270, 66%)
were referred due to upcoming cancer or other immunosuppressive therapy. The
majority (n = 314, 77%) were diagnosed with one or more OIPS. In univariate
analyses, smoking (OR 3.2, 95% CI 1.6-6.4; p = 0.0006), male gender (OR 1.7, 95%
CI 1.1-2.8; p = 0.02), excessive alcohol use (OR 3.0, 95% 1.1-7.9; p = 0.03) and
irregular dental care (OR 4.8, 95% CI 2.6-8.8; p < 0.0001) were risk factors for
OIPS. However, in multivariate analyses, smoking was the only independent risk
factor for OIPS (OR 3.6, 95% CI 1.2-11.8; p = 0.02). CONCLUSIONS: OIPS are common
in patients referred for OIPS clearance, and smoking was identified as an
independent behavioural risk factor for them. These findings highlight the burden
of disease in this patient group and the importance of smoking cessation
encouragement. CLINICAL RELEVANCE: To identify patients at increased risk of
OIPS.
PMID- 29948281
TI - In vitro evaluation by quantitative real-time PCR and culturing of the
effectiveness of disinfection of multispecies biofilms in root canals by two
irrigation systems.
AB - OBJECTIVES: The purpose of this in vitro study was by using quantitative real
time PCR and culturing to determine the effectiveness of two irrigation and
cleaning systems in removing multispecies oral biofilms from root canals.
MATERIAL AND METHODS: Twenty extracted human molars were instrumented to size
#15/.02 and then cleaned with the GentleWave (GW) System. The teeth were
autoclaved to provide the same sterile baseline. The molars were filled with
mixed plaque suspended in BHI and centrifuged to inoculate the biofilms. After 2
weeks of incubation, the teeth were randomly divided into two treatment groups.
In GW group (26 canals), the teeth were further instrumented to size #15/04, and
in PiezoFlow (PF) group (30 canals) to #35/.04. The teeth were then cleaned
either with GW System or ProUltra PiezoFlow Active Ultrasonic System using 3%
sodium hypochlorite NaOCl, 8% EDTA, and sterile water as irrigants. Samples (S1,
S2, and S3) for bacterial cultures were taken from 13 canals before and after
instrumentation and after final cleaning. Quantitative real-time PCR was
performed from all 56 canals, and universal bacterial, one genus, and one species
specific primers were used to determine the presence of microorganisms in samples
from root canals before and after instrumentation and after final cleaning.
Statistical analyses were performed using the Mann-Whitney U test with the
significance level set at P < 0.05. RESULTS: Bacterial culturing from the canal
samples revealed strong reduction of bacteria from S1 to S2 in both groups after
instrumentation and irrigation with water only. No growth was detected in any of
the S3 samples after cleaning in either group. A highly significant reduction in
bacterial DNA was recorded by qPCR for both groups (P < 0.001). GW System showed
more constant and a significantly higher reduction of total microbial DNA (P =
0.007), Enterococcus faecalis DNA (P = 0.011) and Streptococcus spp. DNA (P =
0.029) than the Ultrasonic System. The amount of residual microbial DNA
calculated as an average of residual DNA in each individual canal in PF group was
1.99% and in GW group 0.09%. CONCLUSIONS: While both systems demonstrated a
highly effective reduction of intracanal bacterial DNA, the final total amount
and variation in the number of residual bacterial DNA was significantly smaller
in the GW group. CLINICAL RELEVANCE: Elimination of microbes from the infected
root canal system is regarded as the key for long-term clinical success. While
both GentleWave and Ultrasonic Systems used with NaOCl and EDTA demonstrated a
highly effective reduction of intracanal bacterial DNA; GW produced higher
reduction and better predictability.
PMID- 29948282
TI - Effect of intracanal medicaments on matrix metalloproteinase-9 and vasoactive
intestinal peptide secretion in periapical lesions of re-treated canals: a
randomized controlled clinical study.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of calcium hydroxide
(Ca[OH]2) and chlorhexidine (CHX) gel on matrix metalloproteinase-9 (MMP-9) and
vasoactive intestinal peptide (VIP) secretion in periapical lesions. MATERIALS
AND METHODS: A total of 60 patients were randomly divided into two groups that
were to receive different medications. Pre-and post-treatment samples were
collected from the interstitial fluid of periapical lesions using sterile paper
points. VIP and MMP-9 levels were measured by enzyme-linked immunosorbent assay
kits, and the data were statistically analyzed. RESULTS: Gender and smoking
habits had no effect on the pre- and post-treatment VIP and MMPs levels.
Intragroup analyses revealed that in the Ca(OH)2 group, the post-treatment VIP
level was found to be significantly higher than the pre-treatment VIP level. In
the CHX group, the post-treatment MMP-9 level was significantly higher than the
pre-treatment MMP-9 level. CONCLUSION: According to the results of the present
study, the type of the medication affected the amount of periapical VIP and MMP-9
secretion. CLINICAL RELEVANCE: VIP is a neuropeptide that promotes new bone
formation. Thus, intracanal Ca(OH)2 medication may accelerate the repair process
of bone tissue.
PMID- 29948284
TI - About venous malformations of the facial bones.
PMID- 29948283
TI - Haplotypes of ABCB1 1236C >T (rs1128503), 2677G >T/A (rs2032582), and 3435C >T
(rs1045642) in patients with bullous pemphigoid.
AB - Bullous pemphigoid (BP) constitutes the most prevalent disease in the group of
bullous dermatoses with the autoimmune background. Some authors suggest that
certain cytokines (IL-2, IFN-gamma) may be transported by P-glycoprotein (P-gp),
the product of the ABCB1 gene. ABCB1 polymorphism might affect not only the
effectiveness of treatment with drugs that are P-gp substrates but also
contribute to the development of diseases, including BP. In the present work, we
resolved to conduct a haplotype analysis of ABCB1 in patients with BP and to
answer the question of whether any of the haplotypes are able to affect the
incidence of this entity. The study involved 71 patients with BP and 100 healthy
volunteers. Determination of polymorphisms 1236C > T and 3435C > T in ABCB1 was
carried out with the PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment
Length Polymorphism) method. The 2677G > T/A ABCB1 polymorphism was analyzed with
the allele-specific PCR method. It was observed that the 1236T-2677G-3435T
haplotype occurred with a statistically significantly lower frequency in patients
with BP than in controls (1.4 vs. 10.0%). Carriers of this haplotype were also
shown to have had a low relative risk for BP (OR = 0.13, p = 0.003). Haplotype
analysis of ABCB1 conducted in patients with BP demonstrated that the 1236T-2677G
3435T haplotype may protect against development of this entity.
PMID- 29948285
TI - Integrating basic science in academic cardiology training: two international
perspectives on a common challenge.
AB - Political bodies and professional societies acknowledge that translational
research benefits from researchers trained in both, clinical medicine and basic
science. Yet, few physicians undergoing clinical training in cardiology seek this
dual career (Milewicz et al. J Clin Invest 125:3742-3747, 2015). The reasons are
likely manifold, but with cardiology having become increasingly interventional
and facing economic pressure, how much attention, credit, and encouragement is
given to physicians interested in basic cardiovascular science? Having studied
and worked in hospitals and laboratories, in both Germany and the USA, we aim to
compare in this article how basic science education is currently integrated into
cardiology training at German and US university hospitals, from medical school to
more advanced career stages. By doing so, we hope to provide some outside
perspectives to young physicians and decision makers alike, that may inspire
changes to curricula in the respective countries and around the world.
PMID- 29948287
TI - Follow-up of the first patients with a totally subcutaneous ICD in Germany from
implantation till battery depletion.
AB - BACKGROUND: The subcutaneous ICD is a promising treatment option in patients at
risk for sudden cardiac death. Approved in 2009, the first S-ICD(r) in Germany
was implanted in June 2010. Although large prospective registry studies have
shown safety and efficacy of the system, there is a lack of long-term data with
regard to battery longevity of the S-ICD(r). Therefore, we report follow-up of
our first initial S-ICD(r) cases from implantation till battery depletion.
MATERIALS AND METHODS: All S-ICD(r) patients with device replacement for battery
depletion in our large single-center S-ICD(r) registry were included in this
study. Baseline characteristics, appropriate and inappropriate shocks, and
complications were documented in a median follow-up of 75.9 +/- 6.8 months.
RESULTS: Twenty-eight patients with S-ICD(r) systems were included in this study.
Of these patients, 21 were male and 7 were female, with an overall mean age of
41.9 +/- 12.6 years. Primary prevention of sudden cardiac death was the
indication in 19 patients (67.9%). Ventricular tachycardia was adequately
terminated in two patients (7.1%). In 7 patients, non-sustained ventricular
arrhythmias were not treated. A total of three inappropriate shocks occurred in
three patients (10.7%). Mean time from implantation till battery depletion was
65.8 +/- 8.1 months. Only one patient presented premature elective replacement
criteria because of rapid battery depletion. No lead-related complication
occurred during follow-up and no complications were seen regarding device
replacement. In one patient (3.6%), the system was explanted without replacement
due to patient's preference. CONCLUSION: The estimated battery longevity of S
ICD(r) of about 5 years was reached in all but one patient. Compared to larger S
ICD(r) registry studies, frequency of inappropriate shocks was relatively high in
the initial S-ICD(r) cases. Both technological improvement as well as programming
and operators' experience have led to a reduction of complications. Replacement
of the S-ICD(r) seems to be a safe and effective procedure.
PMID- 29948288
TI - Interventional treatment of paravalvular regurgitation by plug implantation
following prosthetic valve replacement: a single-center experience.
AB - BACKGROUND: Interventional closure of paravalvular leaks (PVL) by plug
implantation has emerged as an alternative to surgical correction, which is
associated with high mortality rates for re-operation. To date, data on
procedural efficacy and clinical outcome after transcatheter closure is sparse.
We present our experience with interventional PVL closure at our site. METHODS
AND RESULTS: From 08/2014 to 10/2016 ten patients (three women, seven men) at
high surgical risk for repeat surgery underwent interventional PVL closure for
severe paravalvular regurgitation (PVR) in 14 procedures at our site. Nine
procedures (64%) were performed for mitral PVLs, five procedures were performed
for aortic PVLs (36%). Mean age of the population treated was 70 +/- 8.6 years
and mean log. Euro-Score I was 27.4 +/- 14.9%. All patients were treated by
implantation of Amplatzer Vascular Plug III occluders. All aortic PVLs were
treated using a retrograde transfemoral access, mitral PVLs were treated using
either a transseptal (8/9) or transapical access (1/9) under 3-dimensional
transesophageal echocardiographic and fluoroscopic guidance. Indication for PVL
closure was the presence of severe heart failure symptoms in all patients (NYHA
class III/IV, n = 14) and additional mechanical hemolytic anemia (n = 5) with a
need for transfusion. Interventional closure of PVL was completely successful in
12 procedures (85%), partially successful in one procedure due to inability to
cross the defect with a wire (7.5%) and failed in one of 14 procedures due to
inability of plug deployment in a very large defect (7.5%). One patient in a
critical clinical condition died within 24 h after procedure due to progressive
cardiogenic shock after procedural failure and refusal of a surgical treatment by
cardiac surgeons. After interventional treatment clinical success with
improvement in NYHA functional class or hemolysis was achieved in 93% (13/14).
Median NYHA class improved significantly from 4 prior to procedure to 2 after PVL
closure (p = 0.0005). Severe PVR was significantly reduced to mild in six
patients and to moderate in three patients after procedure (p = 0.001).
Complications included one hemothorax after transapical access and one
pseudoaneurysm after transfemoral arterial access. In-hospital mortality rate was
20% (2/10) in this high-risk population. After hospital discharge no death
occurred during 30-day follow-up, one patient died during 1-year follow-up after
PVL closure. CONCLUSION: In this single-center series interventional PVL closure
appears promising for patients at high surgical risk with symptomatic
paravalvular regurgitation. Gaining experience in interventional PVL closure at
specialized sites will further improve safety and efficacy of this relatively new
treatment option. All patients should be treated within large clinical registries
to gain more data on mid- and long-term efficacy of transcatheter PVL closure.
PMID- 29948286
TI - Sustained atrial fibrillation increases the risk of anticoagulation-related
bleeding in heart failure.
AB - BACKGROUND: Oral anticoagulation therapy in individuals with atrial fibrillation
(AF) reduces the risk of thromboembolic events at cost of an increased bleeding
risk. Whether anticoagulation-related outcomes differ between patients with
paroxysmal and sustained AF receiving anticoagulation is controversially
discussed. METHODS: In the present analysis of the prospective multi-center
cohort study thrombEVAL, the incidence of anticoagulation-related adverse events
was analyzed according to the AF phenotype. Information on outcome was centrally
recorded over 3 years, validated via medical records and adjudicated by an
independent review panel. Study monitoring was provided by an independent
institution. RESULTS: Overall, the sample comprised 1089 AF individuals, of whom
n = 398 had paroxysmal AF and n = 691 experienced sustained AF. In Cox regression
analysis with adjustment for potential confounders, sustained AF indicated an
independently elevated risk of clinically relevant bleeding compared to
paroxysmal AF [hazard ratio (HR) 1.40 (1.02; 1.93); P = 0.038]. For clinically
relevant bleeding, a significant interaction of the pattern of AF type with
concomitant heart failure (HF) was detected: HRHF 2.45 (1.51, 3.98) vs. HRno HF
0.85 (0.55, 1.34); Pinteraction = 0.003. In HF patients, sustained AF indicated
also an elevated risk of major bleeding [HR 2.25 (1.26, 4.20); P = 0.006]. A
simplified HAS-BLED score incorporating only information on age (> 65 years),
bleeding history, and HF with sustained AF demonstrated better discriminative
performance for clinically relevant bleeding than the original version: AUCHAS
BLED: 0.583 vs. AUCsimplifiedHAS-BLED: 0.642 (P = 0.004). CONCLUSIONS: In HF
patients receiving oral anticoagulation, sustained AF indicates a substantially
elevated risk of bleeding. CLINICAL TRIAL REGISTRATION:
https://clinicaltrials.gov , identifier: NCT01809015.
PMID- 29948290
TI - Cardiac autonomic evaluation in breast cancer patients: role of cytokines and
heart rate recovery.
PMID- 29948289
TI - Current and future aspects of multimodal and fusion imaging in structural and
coronary heart disease.
AB - The procedural success of cardiovascular and structural interventions depends on
adequate pre- and intraprocedural imaging. Multimodal imaging utilizing several
techniques provides added value in terms of procedural planning and efficacy by
combining the individual strength of each imaging modalities. Recently, fusion
imaging as combined "hybrid" procedure of several imaging modalities has gained
some attention. The major advantage consists in the optimized multi-dimensional
view with an excellent spatial resolution and anatomic orientation. The so often
called "anatomical intelligence" already gives prospects towards heart model
derived heart valve construction and individual anatomic conformation. However,
hybrid fusion imaging has the potential to increase safety, accuracy, and
procedural effectiveness in interventional cardiology.This review gives an
overview of the benefits and shortcomings of multimodal and fusion imaging in the
context of pre- and intraprocedural structural and cardiovascular interventions.
It highlights some aspects and thoughts towards cardiovascular imaging of the
future.
PMID- 29948291
TI - Late migration of Edwards SAPIEN 3 transcatheter heart valves: mechanisms and
transcatheter treatment options for a rare phenomenon.
PMID- 29948292
TI - Aortic annulus sizing in stenotic bicommissural non-raphe-type bicuspid aortic
valves: reconstructing a three-dimensional structure using only two hinge points.
AB - Bicuspid aortic valve (BAV) anatomy is becoming an increasingly frequently
encountered challenge in transcatheter aortic valve implantation (TAVI).
Bicommissural non-raphe-type BAV (Sievers and Schmidtke Type 0) is composed
morphologically of two aortic cusps with no raphe and is less common than the
tricommissural or bicommissural raphe-type configurations. Precise annular sizing
is a key step for successful TAVI in BAV. The challenge in bicommissural non
raphe-type BAV is that a three-dimensional structure has to be reconstructed
using only two anatomical hinge points. For this reason, available software are
limited when it comes to bicommissural non-raphe-type BAV. We propose that manual
assessment of the aortic root in bicommissural non-raphe-type BAV using multi
planar reconstruction (MPR) software can be performed successfully by aligning
the two available hinge points and measuring the smallest identifiable annular
dimensions in the transverse plane (Fig. 1). We identified 12 patients with
bicommissural non-raphe-type BAV undergoing TAVI between January 2013 and
December 2017 in our high-volume institution. Our novel sizing strategy was
employed prospectively in three patients-with good clinical outcomes-and
evaluated retrospectively in the remainder (Table 1). No patient suffered a
central major vascular complication or required new permanent pacemaker
implantation. Device success occurred in all patients except one (post-procedural
echocardiographic transvalvular gradient of 23 mmHg). In the retrospectively
assessed cases, the novel annulus measure was concordant with the implanted THV
size in 7 out of 9 procedures and, importantly, did not overestimate the annulus
dimensions in any case. Furthermore, in two balloon-expandable THV cases the new
measure may, in retrospect, have prompted consideration of a smaller implant
size. To be noted, balloon sizing of the aortic annulus has additional value when
selecting the valve size in BAV anatomy. Further prospective validation of this
novel MDCT sizing technique is required.
PMID- 29948293
TI - Reply to the letter "Cardiac autonomic evaluation in breast cancer patients: role
of cytokines and heart rate recovery".
PMID- 29948294
TI - Double-chambered left ventricle in a patient with chest pain.
PMID- 29948295
TI - Importance and accuracy of intraoperative frozen section diagnosis of the
resection margin for effective carmustine wafer implantation.
AB - For effective implantation of carmustine (BCNU) wafers, it is important to
determine the order of priority with reference to the intraoperative frozen
section diagnosis of the resection margin (IOFM). The accuracy of IOFM and
patterns of tumor recurrence with implantation of BCNU wafers were studied
retrospectively. Forty-six cases of newly diagnosed malignant glioma were
evaluated. Tumors were resected after intraoperative frozen section diagnosis
(IOFD). IOFM was performed for resection walls and evaluated on a three-level
scale (-, no tumor invasion; 1+, minor cell invasion; 2+, evident cell invasion).
The results were used for effective BCNU wafer implantation. The IOFM sections
were then thawed, frozen-paraffin marginal (FPM) sections were prepared, and IOFM
was evaluated with FPM sections. The accuracy of IOFD grading was compared to
that of the formalin fixed paraffin-embedded section and was 76.1%. The accuracy
of IOFM was compared with the FPM section in 148 specimens from 42 patients. The
IOFM accuracy was 80.4%. BCNU wafers were implanted in 25 patients and there was
recurrence in 15. Local recurrence was seen in 40% (6 patients). However, there
was no recurrence immediately below the BCNU wafers. With properly performed
IOFM, BCNU wafers can be efficiently implanted, and local recurrence immediately
below the BCNU wafers can be inhibited.
PMID- 29948297
TI - Characteristics of women calling the PANDA Perinatal Anxiety & Depression
Australia National Helpline: a cross-sectional study.
AB - The PANDA Perinatal Anxiety & Depression Australia National Helpline provides
support for people affected by perinatal mental health issues. To describe the
characteristics of women contacting the Helpline, specifically callers' health,
past history and assessed risk factors. Analysis of routinely collected de
identified data of women making initial calls between July 2010 and October 2013.
Five thousand eight hundred eighteen women made an initial call to the Helpline.
Most were between 25 and 40 years old (79%) and married/partnered (94%); 52% were
having or had their first child; and 23% were pregnant. Over half had no prior
mental health diagnosis at the time of their initial call, and 40% were assessed
as 'high needs'-experiencing significant bio-psychosocial symptoms, complex
situations and/or inadequate care and support. There was a 70% increase in calls
to PANDA over the data collection period. Concerns recorded by PANDA staff from
the initial risk assessment included inadequate treatment for a mental health
condition (31%), women not feeling connected to their baby (31%), low functioning
(26%) and general thoughts of suicide (18%). The Helpline experienced a
significant increase in demand during the study period, and a substantial
proportion of callers had complex mental health needs. PANDA plays a major role
in providing support to a large number of women experiencing perinatal mental
health problems.
PMID- 29948296
TI - Sensory laterality in affiliative interactions in domestic horses and ponies
(Equus caballus).
AB - Many studies have been carried out into both motor and sensory laterality of
horses in agonistic and stressful situations. Here we examine sensory laterality
in affiliative interactions within four groups of domestic horses and ponies (N =
31), living in stable social groups, housed at a single complex close to Vienna,
Austria, and demonstrate for the first time a significant population preference
for the left side in affiliative approaches and interactions. No effects were
observed for gender, rank, sociability, phenotype, group, or age. Our results
suggest that right hemisphere specialization in horses is not limited to the
processing of stressful or agonistic situations, but rather appears to be the
norm for processing in all social interactions, as has been demonstrated in other
species including chicks and a range of vertebrates. In domestic horses,
hemispheric specialization for sensory input appears not to be based on a
designation of positive versus negative, but more on the perceived need to
respond quickly and appropriately in any given situation.
PMID- 29948298
TI - Website-visibility of Neurosurgical Centers in Europe. A necessary tool for
enhancing scientific network cooperation and information distribution: letter to
the editor.
PMID- 29948299
TI - Cranial nerve deficits in giant cavernous carotid aneurysms and their relation to
aneurysm morphology and location.
AB - BACKGROUND: Giant cavernous carotid aneurysms (GCCAs) usually exert substantial
mass effect on adjacent intracavernous cranial nerves. Since predictors of
cranial nerve deficits (CNDs) in patients with GCCA are unknown, we designed a
study to identify associations between CND and GCCA morphology and the location
of mass effect. METHODS: This study was based on data from the prospective
clinical and imaging databases of the Giant Intracranial Aneurysm Registry. We
used magnetic resonance imaging and digital subtraction angiography to examine
GCCA volume, presence of partial thrombosis (PT), GCCA origins, and the location
of mass effect. We also documented whether CND was present. RESULTS: We included
36 GCCA in 34 patients, which had been entered into the registry by eight
participating centers between January 2009 and March 2016. The prevalence of CND
was 69.4%, with one CND in 41.7% and more than one in 27.5%. The prevalence of PT
was 33.3%. The aneurysm origin was most frequently located at the anterior genu
(52.8%). The prevalence of CND did not differ between aneurysm origins (p =
0.29). Intracavernous mass effect was lateral in 58.3%, mixed medial/lateral in
27.8%, and purely medial in 13.9%. CND occurred significantly more often in GCCA
with lateral (81.0%) or mixed medial/lateral (70.0%) mass effect than in GCCA
with medial mass effect (20.0%; p = 0.03). After adjusting our data for the
effects of the location of mass effect, we found no association between the
prevalence of CND and aneurysm volume (odds ratio (OR) 1.30 (0.98-1.71); p =
0.07), the occurrence of PT (OR 0.64 (0.07-5.73); p = 0.69), or patient age (OR
1.02 (95% CI 0.95-1.09); p = 0.59). CONCLUSIONS: Distinguishing between medial
versus lateral location of mass effect may be more helpful than measuring
aneurysm volumes or examining aneurysm thrombosis in understanding why some
patients with GCCA present with CND while others do not. CLINICAL TRIAL
REGISTRATION NO: NCT02066493 ( clinicaltrials.gov ).
PMID- 29948301
TI - Use of ultrasound and targeted physiotherapy in the management of a nerve suture
performed under joint flexion.
AB - BACKGROUND: In 1915, when Delorme described three general requirements for
successful nerve repair-(1) resecting scar until a healthy bed is secured, (2)
excising damaged nerve until healthy stumps are reached, and (3) placing tension
free sutures, either by adequately mobilizing adjacent joints or nerve grafting
his work was heavily criticized. One century later, history has vindicated all
but one of these claims. Flexing adjacent joints to avoid nerve grafts remains
controversial, though this practice has increased in recent years. METHODS: An 11
year-old male suffered a penetrating domestic accident that resulted in complete
foot drop. At surgery, a 6-cm gap was treated with direct nerve sutures, for
which the knee was maintained in 60 degrees flexion in a cast. To avoid damage
to the nerve sutures, ultrasound and an intense, though cautious physiotherapy
program were employed to guide the progression of knee extension. RESULTS: The
patient started to show clear signs of peroneal motor function recovery within 3
months of surgical repair, and almost complete recovery by 4 months
postoperatively. CONCLUSIONS: Using physiotherapy and ultrasound might validate
the classic joint-flexion technique in select patients with lower-limb nerve
injuries.
PMID- 29948302
TI - Crohn's disease-specific mortality: a 30-year cohort study at a tertiary referral
center in Japan.
AB - BACKGROUND: In this study, survival and cause of death were investigated in
patients with Crohn's disease (CD) at a tertiary referral center. METHODS: A
database was created based on the medical records of 1108 CD patients who had a
history of visiting our hospital to investigate background characteristics,
cumulative survival rates from diagnosis, causes of death, and the standardized
mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey
of patients followed up inadequately was also conducted. The cumulative survival
rate from diagnosis was determined using the life table method and compared with
that of a sex- and age-matched population model from the year 2000. RESULTS: The
study included 1108 patients whose mean age at diagnosis was 25.6 +/- 10.8 years.
The mean duration of follow-up was 14.6 +/- 9.4 years, and there were 52 deaths.
The cumulative survival rate was significantly lower 25 years after the diagnosis
of CD (91.7%) than in the standard population model (95.7%). SMRs for both all
causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7;
95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially
high for small intestine and colorectal cancers, gastrointestinal diseases
including intestinal failure (IF), perioperative complications, and amyloidosis.
CONCLUSION: The SMRs for both all causes and CD-specific causes were high in CD
patients. CD-specific causes including intestinal cancer, IF, perioperative
complications, and amyloidosis showed especially high SMRs.
PMID- 29948303
TI - Surface microstructures are associated with mutational intratumoral heterogeneity
in colorectal tumors.
AB - BACKGROUND: Recent studies revealed that colorectal tumors are composed of
genetically diverse subclones. We aimed to clarify whether the surface
microstructures of colorectal tumors are associated with genetic intratumoral
heterogeneity (ITH). METHODS: The surface microstructures (pit patterns) of
colorectal tumors were observed using magnifying endoscopy, and biopsy specimens
were obtained from respective areas when tumors exhibited multiple pit patterns.
A total of 711 specimens from 477 colorectal tumors were analyzed for BRAF, KRAS
and TP53 mutations using pyrosequencing and direct sequencing. A panel of cancer
related genes was analyzed through targeted sequencing in 7 tumors. RESULTS:
Colorectal tumors with multiple pit patterns exhibited more advanced pit patterns
and higher frequencies of KRAS and/or TP53 mutations than tumors with a single
pit pattern. In tumors with multiple pit patterns, mutations were observed as
public (common to all areas) or private (specific to certain areas), and private
KRAS and/or TP53 mutations were often variable and unrelated to the pit pattern
grade. Notably, invasive CRCs frequently exhibited public TP53 mutations, even in
adenomatous areas, which is indicative of their early malignant potential.
Targeted sequencing revealed additional public and private mutations in tumors
with multiple pit patterns, indicating their single clonal origin. CONCLUSIONS:
Our results suggest intratumoral pit pattern variation does not simply reflect
the process of colorectal tumor evolution, but instead represents genetically
diverse subclones, and this diversity may be associated with malignant potential.
PMID- 29948305
TI - Increase in the skeletal muscle mass to body fat mass ratio predicts the decline
in transaminase in patients with nonalcoholic fatty liver disease.
AB - BACKGROUND: The aim of this retrospective study was to determine the effect of
skeletal muscle and body fat on liver function in patients with nonalcoholic
fatty liver disease (NAFLD) diagnosed by liver biopsy. METHODS: Among the 219
patients with NAFLD enrolled in this study was a cohort of 139 patients who had
their body composition measured with Inbody720 at baseline and at >= 1 year
postbaseline, to elucidate the relationship between liver function and changes in
skeletal muscle and body fat mass. Multivariate analysis was used to identify
factors influencing low skeletal muscle mass index (SMI, defined as 7 kg/m2 in
men, and 5.7 kg/m2 in women) and the skeletal muscle mass to body fat mass ratio
(SF ratio). RESULTS: Of the 219 patients enrolled, 27 (12.3%) had a low SMI.
Patient age (> 70 years) and female gender were identified as risk factors for
low SMI. Hepatic fibrosis was not associated with SMI. In the cohort followed up
at baseline and 12 months later, transaminase activity, body fat mass, and SMI
significantly decreased over time. Changes in the SF ratio were significantly
associated with changes in liver function. An increase in the SF ratio [hazard
ratio (HR) 10.99 in men, 6.849 in women] was a predictor of reduced ALT,
independent of age and other backgrounds. CONCLUSIONS: In the patients with
NAFLD, SMI was decreased, even in the early stages of NAFLD. Therapeutic
strategies for NAFLD require a reduction in body fat mass and the maintenance of
skeletal muscle is also needed.
PMID- 29948304
TI - A case-control study of the risk of upper gastrointestinal mucosal injuries in
patients prescribed concurrent NSAIDs and antithrombotic drugs based on data from
the Japanese national claims database of 13 million accumulated patients.
AB - BACKGROUND: We aimed to identify the adverse effects of nonsteroidal anti
inflammatory drugs (NSAIDs) and antithrombotics on the upper gastrointestinal
(GI) mucosa in a clinical setting as a case-control study using a large-scale
medical database in Japan. METHODS: We evaluated the risk of upper GI mucosal
injuries in patients receiving NSAIDs and antithrombotics using the Japan Medical
Data Center claims database with data for 13 million accumulated patients, from
January 2009 to December 2014. Endoscopically evaluated upper GI mucosal injuries
were peptic ulcers (n = 143,271), upper GI bleeding (n = 10,545), and
gastroesophageal reflux disease (n = 154,755). For each patient, ten controls
were matched by age, sex, and diagnosis month. RESULTS: The odds ratio (OR) for
peptic ulcers was 1.45, 1.31, 1.50, 1.53, and 1.62; for upper GI bleeding: 1.76,
1.62, 1.96, 1.82, and 2.38; and for gastroesophageal reflux disease: 1.54, 1.41,
1.89, 1.67, and 1.91 for NSAIDs, COX-2 selective inhibitors, low-dose aspirin,
antiplatelet drugs, and anticoagulants, respectively (all statistically
significant: P < 0.001). Polypharmacy with NSAIDs and antithrombotic drugs
increased the risk of upper GI injuries compared with single-drug therapy. The
injury risk was also increased by lifestyle-related diseases, including diabetes
mellitus and hyperlipidemia. CONCLUSIONS: This case-control study using the large
organized Japanese claims database provided the risk of upper GI mucosal injuries
in patients receiving NSAIDs and antithrombotic drugs.
PMID- 29948306
TI - Autoimmune abnormalities of the alternative complement pathway in
membranoproliferative glomerulonephritis and C3 glomerulopathy.
AB - Membranoproliferative glomerulonephritis (MPGN) is a rare chronic kidney disease
associated with complement activation. Recent immunofluorescence-based
classification distinguishes between immune complex (IC)-mediated MPGN, with
glomerular IgG and C3 deposits, and C3 glomerulopathies (C3G), with predominant
C3 deposits. Genetic and autoimmune abnormalities causing hyperactivation of the
complement alternative pathway have been found as frequently in patients with
immune complex-associated MPGN (IC-MPGN) as in those with C3G. In the last
decade, there have been great advances in research into the autoimmune causes of
IC-MPGN and C3G. The complement-activating autoantibodies called C3-nephritic
factors (C3NeFs), which are present in 40-80% of patients, form a heterogeneous
group of autoantibodies that stabilise the C3 convertase or the C5 convertase of
the alternative pathway or both. A few patients, mainly with IC-MPGN, carry
autoantibodies directed against the two components of the alternative pathway C3
convertase, factors B and C3b. Finally, autoantibodies against factor H, the main
regulator of the alternative pathway, have been reported in a small proportion of
patients with IC-MPGN or C3G. The identification of distinct pathogenetic
patterns leading to kidney injury and of targets in the complement cascade may
pave the way for tailored therapies for IC-MPGN and C3G, with specific complement
inhibitors in the development pipeline.
PMID- 29948307
TI - Urinary epidermal growth factor as a prognostic marker for the progression of
Alport syndrome in children.
AB - BACKGROUND: Alport syndrome is a rare hereditary kidney disease manifested with
progressive renal failure. Considerable variation exists in terms of disease
progression among patients with Alport syndrome. Identification of patients at
high risk of rapid progression remains an unmet need. Urinary epidermal growth
factor (uEGF) has been shown to be independently associated with risk of
progression to adverse kidney outcome in multiple independent adult chronic
kidney disease (CKD) cohorts. In this study, we aim to assess if uEGF is
associated with kidney impairment and its prognostic value for children with
Alport syndrome. METHODS: One hundred and seventeen pediatric patients with
Alport syndrome and 146 healthy children (3-18 years old) were included in this
study. uEGF was measured in duplicates in baseline urine samples using ELISA
(R&D) and concentration was normalized by urine creatinine (uEGF/Cr). In patients
with longitudinal follow-up data (n = 38), progression was defined as
deteriorated kidney function (CKD stage increase) during follow-up period (follow
up length is about 31 months in average). The association of baseline uEGF/Cr
level with estimated glomerular filtration rate (eGFR) slope and Alport syndrome
patients' progression to a more advanced CKD stage during the follow-up period
was used to evaluate the prognostic value of the marker. RESULTS: We found that
uEGF/creatinine (uEGF/Cr) decreases with age in pediatric patients with Alport
syndrome with a significantly faster rate than in healthy children of the same
age group. uEGF/Cr is significantly correlated with eGFR (r = 0.75, p < 0.001),
after adjustment for age. In 38 patients with longitudinal follow-up, we observed
a significant correlation between uEGF/Cr and eGFR slope (r = 0.58, p < 0.001).
Patients with lower uEGF/Cr level were at increased risk of progression to a
higher CKD stage. uEGF/Cr was able to distinguish progressors from non
progressors with an AUC of 0.88, versus 0.77 by eGFR and 0.81 by 24-h urinary
protein (24-h UP). CONCLUSIONS: Our study suggests that uEGF/Cr is a promising
biomarker for accelerated kidney function decline in pediatric patients with
Alport syndrome. It may help to identify patients at high risk of progression for
targeted clinical care and improve the patients' stratification in interventional
trials.
PMID- 29948308
TI - Ambulatory blood pressure monitoring and neurocognitive function in children with
primary hypertension.
AB - BACKGROUND: Children with primary hypertension have been reported to have
diminished scores in measures of cognition. However, little is known about the
relative correlation between office and ambulatory blood pressure (BP) and
neurocognitive test performance, and whether short-term BP variability is
associated with decreased neurocognitive function. We sought to determine whether
ambulatory BP monitoring (ABPM) was more strongly associated with neurocognitive
test performance compared with office BP, and whether increased short-term BP
variability was associated with lower neurocognitive scores. METHODS: Seventy
five subjects ages 10-18 years, with untreated primary hypertension, and 75
matched normotensive controls completed neurocognitive testing. All subjects had
office BP and ABPM prior to neurocognitive testing. RESULTS: On multivariate
analyses, there was no significant association between office BP and
neurocognitive tests. However, several ABPM parameters were significantly
associated with neurocognitive test scores in the lower quartile, in particular
24 h SBP load and wake systolic blood pressure (SBP) index [Rey Auditory Verbal
learning Test (RAVLT) List A Trial 1, 24 h SBP load, odds ratio (OR) = 1.02, wake
SBP index, OR = 1.06; List A Total, 24 h SBP load, OR = 1.02, wake SBP index, OR
= 1.06; Short Delay Recall, wake SBP index, OR = 1.06; CogState Maze delayed
recall, 24 h SBP load, OR = 1.03, wake SBP index, OR = 1.08; Grooved Pegboard, 24
h SBP load, OR = 1.02; all p < 0.05]. In contrast, short-term BP variability
measures were not associated with neurocognitive test performance. CONCLUSIONS:
ABPM is superior to office BP in distinguishing hypertensive youth with lower
neurocognitive test performance.
PMID- 29948309
TI - Risk factors and inpatient outcomes associated with acute kidney injury at
pediatric severe sepsis presentation.
AB - BACKGROUND: Little data exist on acute kidney injury (AKI) risk factors in
pediatric sepsis. We identified risk factors and inpatient outcomes associated
with AKI at sepsis recognition in children with severe sepsis. METHODS:
Retrospective, cross-sectional study with inpatient outcome description of 315
patients > 1 month to < 20 years old with severe sepsis in a pediatric intensive
care unit over 3 years. Exposures included demographics, vitals, and laboratory
data. The primary outcome was kidney disease: Improving Global Outcomes
creatinine-defined AKI within 24 h of sepsis recognition. Factors associated with
AKI and AKI severity were identified using multivariable Poisson and multinomial
logistic regression, respectively. RESULTS: AKI was present in 42% (133/315) of
severe sepsis patients, and 26% (83/315) had severe (stage 2/3) AKI. In
multivariable-adjusted analysis, hematologic/immunologic comorbidities,
malignancies, chronic kidney disease (CKD), abdominal infection, admission
illness severity, and minimum systolic blood pressure (SBP) <= 5th percentile for
age and sex within 24 h of sepsis recognition were associated with AKI. Factors
associated with mild AKI were CKD and abdominal infection, while factors
associated with severe AKI were younger age, hematologic/immunologic
comorbidities, malignancy, abdominal infection, and minimum SBP <= 5th
percentile. Patients with AKI had increased hospital mortality (17 vs. 8%, P =
0.02) and length of stay [median 20 (IQR 10-47) vs. 16 days (IQR 7-37), P =
0.03]. CONCLUSIONS: In pediatric severe sepsis, AKI is associated with age,
comorbidities, infection characteristics, and hypotension. Future evaluation of
risk factors for AKI progression during sepsis is warranted to minimize AKI
progression in this high-risk population.
PMID- 29948310
TI - Parental health literacy and progression of chronic kidney disease in children.
AB - BACKGROUND: Limited health literacy has been associated with adverse outcomes in
children. We evaluated this association in the setting of chronic kidney disease
(CKD). METHODS: We assessed the parental health literacy of 367 children enrolled
in the Chronic Kidney Disease in Children (CKiD) Study, using the Short Test of
Functional Health Literacy (STOFHLA). We evaluated the association between
parental health literacy and CKD progression, defined as time to the composite
event of renal replacement therapy (RRT, dialysis, or kidney transplant) or 50%
decline in estimated glomerular filtration rate (eGFR). RESULTS: Median CKiD
participant age was 9.5 years, 63% were male, and 59% non-Hispanic white. Median
eGFR at baseline was 63 ml/min/1.73 m2, and median urine protein-to-creatinine
ratio was 0.22. The median STOFHLA score was 98. Over a median follow-up of 3.7
years, the overall CKD progression rate was 2.8 per 100 person-years. After
adjustment for demographic and clinical factors, the relative time to CKD
progression was 28% longer per 1 SD increase in STOFHLA score (relative time, 95%
CI, 1.28, 1.06-1.53). CONCLUSIONS: In this cohort of children with CKD, higher
parental health literacy was associated with a nearly 30% longer time to the
composite CKD progression outcome.
PMID- 29948311
TI - Correction to: Postnatal imaging of prenatally detected hydronephrosis-when is
voiding cystourethrogram necessary?
AB - The original publication contained an erroneous version of Table 3 with incorrect
data regarding ureteral visibility. The authors apologize for any inconvenience
caused by their mistake and are pleased to present the corrected table here.
PMID- 29948312
TI - Terrestrial birds in coastal environments: metabolic rate and oxidative status
varies with the use of marine resources.
AB - Life in saline environments represents a major physiological challenge for birds,
particularly for passerines that lack nasal salt glands and hence are forced to
live in environments that do not contain salty resources. Increased energy costs
associated with increased salt intake, which in turn increases the production of
reactive oxygen species, is likely a major selection pressure for why passerines
are largely absent from brackish and marine environments. Here we measured basal
metabolic rates (BMR) and oxidative status of free-ranging individuals of three
species of Cinclodes, a group of passerine birds that inhabit marine and
freshwater habitats in Chile. We used a combination of carbon, nitrogen, and
hydrogen isotope data from metabolically active (blood) and inert (feathers)
tissues to estimate seasonal changes in marine resource use and infer altitudinal
migration. Contrary to our expectations, the consumption of marine resources did
not result in higher BMR values and higher oxidative stress. Specifically, the
marine specialist C. nigrofumosus had lower BMR than the other two species (C.
fuscus and C. oustaleti), which seasonally switch between terrestrial and marine
resources. C. fuscus had significantly higher total antioxidant capacity than the
other two species (C. nigrofumosus and C. oustaleti) that consumed a relatively
high proportion of marine resources. Nearly all studies examining the effects of
salt consumption have focused on intraspecific acclimation via controlled
experiments in the laboratory. The mixed results obtained from field- and lab
based studies reflect our poor understanding of the mechanistic link among hydric
salt balance, BMR, and oxidative stress in birds.
PMID- 29948313
TI - Multiple predator effects on juvenile prey survival.
AB - Predicting multiple predator effects (MPEs) on shared prey remains one of the
biggest challenges in ecology. Empirical evidence indicates that interactions
among predators can alter predation rates and modify any expected linear effects
on prey survival. Knowledge on predator density, identity and life-history traits
is expected to help predict the behavioral mechanisms that lead to non-linear
changes in predation. Yet, few studies have rigorously examined the effects of
predator-predator interactions on prey survival, particularly with marine
vertebrate predators. Using an additive-substitutive design, we experimentally
paired reef piscivores with different hunting mode [active predator,
Pseudochromis fuscus (F); ambush predators, Cephalopholis boenak (B), Epinephelus
maculatus (M)] to determine how behavioral interactions modified their combined
impacts on damselfish prey. Results showed that behavioral patterns among
predators matched those predicted from their hunting mode. However, it was the
identity of the predators what determined the strength of any positive or
negative interactions, and thus the nature and magnitude of MPEs on prey survival
(i.e., risk-enhancing effects: treatments BB, MM and FM; risk-reducing: BM; and
linear effects: FF, FB). Given the specificity of predator-predator interactions,
none of the predators were fully functionally redundant. Even when two species
seemed substitutable (i.e., predators F and M), they led to vastly diverse
effects when paired with additional predator species (i.e., B). We concluded that
knowledge of the identity of the predator species and the behavioral interactions
among them is crucial to successfully predict MPEs in natural systems.
PMID- 29948314
TI - Flower colour within communities shifts from overdispersed to clustered along an
alpine altitudinal gradient.
AB - Altitudinal gradients are interesting models to test the effect of biotic and
abiotic drivers of floral colour diversity, since an increase in UV irradiance,
decrease of pollinator availability and shifts from bee- to fly-pollination in
high relative to low altitudes are expected. We tested the effect of altitude and
phylogeny, using several chromatic and achromatic colour properties, UV
reflectance and pollinators' discrimination capacity (Apis mellifera, Bombus
terrestris, Musca domestica and Eristalis tenax), to understand the floral colour
diversity in an alpine altitudinal gradient. All colour properties were weakly
related to phylogeny. We found a shift from overdispersed floral colours and high
chromatic contrast with the background (for bees) in the low altitude, to
clustered floral colours (UV and green range for bees and flies) and clustered
chromatic and achromatic properties in the high altitude. Different from flies,
bees could discriminate floral colours in all altitudinal ranges. Low altitudes
are likely to exhibit suitable conditions for more plant species, increasing
competition for pollinators and floral colour divergence. Conversely, the
increase in UV irradiance in high altitudes may filter plants with specific
floral UV-reflectance patterns. Overall, floral colour diversity suggests that
both biotic (pollinator fauna) and abiotic (UV irradiance) drivers shape floral
communities, but their importance changes with altitude.
PMID- 29948315
TI - Litter quality, dispersal and invasion drive earthworm community dynamics and
forest soil development.
AB - In temperate deciduous forests of eastern USA, most earthworm communities are
dominated by invasive species. Their structure and functional group composition
have critical impacts on ecological properties and processes. However, the
factors determining their community structure are still poorly understood, and
little is known regarding their dynamics during forest succession and the
mechanisms leading to these changes. Earthworm communities are usually assumed to
be stable and driven by vegetation. In contrast, the importance of dispersal and
ecological drift is seldom acknowledged. By analyzing a 19-year dataset collected
from forest stands in eastern USA, we demonstrated that on a decadal timescale,
earthworm community dynamics are shaped by the interplay of selection, dispersal,
and ecological drift. We highlighted that forests at different successional
stages have distinct earthworm species and functional groups as a result of
environmental filtering through leaf litter quality. Specifically, young forests
are characterized by soil-feeding species that rely on relatively fresh soil
organic matter derived from fast-decomposing litter, whereas old forests are
characterized by those feeding on highly processed soil organic matter derived
from slow-decomposing litter. In addition, year-to-year species gains and losses
are primarily driven by dispersal from regional to local species pools, and by
local extinction resulted from competition and ecological drift. We concluded
that with continued dispersal of European species and the recent "second wave" of
earthworm invasion by Asian species from the surrounding landscape, earthworms at
the investigated forests are well-established, and will remain as the major
drivers of soil development for the foreseeable future.
PMID- 29948316
TI - Facilitating your replacement? Ecosystem engineer legacy affects establishment
success of an expanding competitor.
AB - Interactions with resident species can affect the rate that expanding species
invade novel areas. These interactions can be antagonistic (biotic resistance),
where resident species hinder invasive establishment, or facilitative (biotic
assistance), where residents promote invasive establishment. The predominance of
resistance or assistance could vary with the abiotic context. We examined how the
effects of a resident ecosystem engineer interact with abiotic stress to resist
or assist the establishment of an expanding competitor. In Florida salt marshes,
native cordgrass, Spartina alterniflora, is an influential ecosystem engineer
that, when dead, exerts a legacy effect by forming persistent wrack patches. We
examined how the legacy effect of Spartina wrack varies with spatial context and
abiotic conditions to influence establishment of the northward-expanding black
mangrove, Avicennia germinans. Field surveys documented that Spartina wrack and
Avicennia propagules co-occur in the high intertidal zone, and we conducted two
outdoor mesocosm experiments to investigate this association. Wrack positively
affected propagule establishment when propagules were beneath wrack, but
negatively affected establishment when propagules were above wrack. The abiotic
tidal regime influences the magnitude of wrack effects by controlling ambient
moisture, and the positive and negative effects of wrack were stronger in low
moisture conditions that simulated desiccation stress during harsh neap tides.
Thus, the same resident engineer can either resist or assist an expanding
competitor and the magnitude of these effects depends on abiotic conditions. We
propose that under harsh conditions, there is greater scope for an engineer's
mediating influence to affect associated species, both positively and negatively.
PMID- 29948317
TI - Temporal records of diet diversity dynamics in individual adult female Steller
sea lion (Eumetopias jubatus) vibrissae.
AB - Detailed information on the nutrition of free-ranging mammals contributes to the
understanding of life history requirements, yet is often quite limited temporally
for most species. Reliable dietary inferences can be made by analyzing the stable
carbon (C) and nitrogen (N) isotopic values (delta13C and delta15N) of some
consumer tissues; exactly which tissue is utilized dictates the inferential
scope. Steller sea lion (SSL) vibrissae are grown continuously without shedding
and thus provide a continuous multi-year record of dietary consumption. We
applied a novel kernel density approach to compare the delta13C and delta15N
values along the length of SSL vibrissae with delta13C and delta15N distributions
of potential prey species. This resulted in time-series of proportion estimates
of dietary consumption for individual SSL. Substantial overlap in delta13C and
delta15N distributions for prey species prevented a discrete species-scale
assessment of SSL diets; however, a post hoc correlational analysis of diet
proportion estimates revealed grouping by trophic level. Our findings suggest
that adult female SSL diets in the western and central Aleutian Islands shift
significantly according to season: diets contain a higher proportion of lower
trophic level species (Pacific Ocean perch, northern rockfish, Atka mackerel and
walleye pollock) in the summer, whereas in the winter SSL consume a much more
diverse diet which includes a greater proportion of higher trophic level species
(arrowtooth flounder, Kamchatka flounder, darkfin sculpin, Pacific cod, Pacific
octopus, rock sole, snailfish, and yellow Irish lord).
PMID- 29948318
TI - The effects of food stoichiometry and temperature on copepods are mediated by
ontogeny.
AB - Climate change is warming the oceans, increasing carbon dioxide partial pressure
and reducing nutrient recycling from deep layers. This will affect carbon (C) and
phosphorus (P) availability in the oceans, thus, altering the balance between the
nutrient content of consumers and their food resource. The combined effects of
food quality and temperature have been investigated for adult copepods; however,
nauplii, the early developmental stages of copepods, often far outnumber adults,
grow more rapidly and have a higher phosphorus body content and demand than later
life stages. Consequently, ontogeny may affect how copepods respond to the
combined stressors of increasing temperature and altered food stoichiometry. We
conducted temperature-controlled experiments (24, 28 and 32 degrees C) where
Parvocalanus crassirostris was fed either a P-replete or a P-limited
phytoplankton food source. Reduced survival of nauplii and copepodites at the
highest temperature was ameliorated when fed P-replete food. At higher
temperatures, copepodite growth remained stable, but internal C:P stoichiometry
diverged in the direction of phytoplankton C:P, suggesting that increased
temperature affected copepodite stoichiometric homeostasis. In contrast, naupliar
P content increased with temperature and naupliar growth was P limited,
suggesting nauplii required additional phosphorus at higher temperatures. We
conclude that resource stoichiometry plays a key role in how copepod survival and
growth are impacted by temperature, and that ontogeny mediates these responses.
Our results suggest that as the extent of warming oceans and phytoplankton
nutrient limitation increase, copepod survival and the growth of early life
stages may decline.
PMID- 29948319
TI - The effect of predator presence on the behavioral sequence from host selection to
reproduction in an invulnerable stage of insect prey.
AB - Predator-prey interactions primarily focus on prey life-stages that are consumed.
However, animals in less vulnerable life-stages might also be influenced by the
presence of a predator, making our understanding of predation-related impacts
across all life-stages of prey essential. It has been previously demonstrated
that Podisus maculiventris is a voracious predator of eggs and larvae of
Leptinotarsa decemlineata, and that larvae will alter their behavior to avoid
predation. However, the adult beetles are not readily consumed by P.
maculiventris, raising the question of whether they will respond to predators to
protect themselves or their offspring. Here, we examine the effect of predation
risk by P. maculiventris, on three adult behaviors of L. decemlineata;
colonization, oviposition, and feeding, and the resulting impact on host plant
damage. In an open-field test, there was no difference in natural beetle
colonization between plots with predation risk and control treatments. However,
subsequent host plant damage by adult beetles was 63.9% less in predation risk
treatments. Over the lifetime of adult beetles in field mesocosms, per capita
feeding was 23% less in the predation risk treatment. Beetle oviposition was 37%
less in the presence of predators in a short-term, greenhouse assay, and
marginally reduced in longer term field mesocosms. Our results indicate that
predation risk can drive relatively invulnerable adult herbivores to adjust
behaviors that affect themselves (feeding) and their offspring (oviposition).
Thus, the full impact of predator presence must be considered across the prey
life cycle.
PMID- 29948320
TI - Radiation exposure to the surgeon during minimally invasive spine procedures is
directly estimated by patient dose.
AB - PURPOSE: Radiation exposure is a necessary component of minimally invasive spine
procedures to augment limited visualization of anatomy. The surgeon's exposure to
ionizing radiation is not easily recognizable without a digital dosimeter
something few surgeons have access to. The aim of this study was to identify an
easy alternative method that uses the available radiation dose data from the C
arm to accurately predict physician exposure. METHODS: The senior surgeon wore a
digital dosimeter during all minimally invasive spine fusion procedures performed
over a 12-month period. Patient demographics, procedure information, and
radiation exposure throughout the procedure were recorded. RESULTS: Fifty-five
minimally invasive spine fusions utilizing 330 percutaneous screws were included.
Average radiation dose was 0.46 Rad/screw to the patient. Average radiation
exposure to the surgeon was 1.06 +/- 0.71 MUSv/screw, with a strong positive
correlation (r = 0.77) to patient dose. The coefficient of determination (r2) was
0.5928, meaning almost two-thirds of the variability in radiation exposure to the
surgeon is explained by radiation exposure to the patient. CONCLUSIONS: Intra
operative radiation exposure to the patient, which is easily identifiable as a
continuously updated fluoroscopic monitor, is a reliable predictor of radiation
exposure to the surgeon during percutaneous screw placement in minimally invasive
spinal fusion surgery and therefore can provide an estimate of exposure without
the use of a dosimeter. With this, a surgeon can better understand the magnitude
of their exposure on a case-by-case basis rather than on a quarterly basis, or
more likely, not at all. These slides can be retrieved under Electronic
Supplementary Material.
PMID- 29948321
TI - A new "keyhole" approach for multilevel anterior lumbar interbody fusion: the
perinavel approach-technical note and literature review.
AB - PURPOSE: The purpose of this study is to evaluate the feasibility and the safety
of a new skin incision for minimally invasive anterior lumbar interbody fusion
(ALIF): the perinavel incision. METHODS: Demographic and clinical data from
patients who underwent ALIF with the perinavel incision were collected.
Indications to surgery, preoperative symptoms, radiological data, number of
treated levels, intraoperative and early postoperative complications and wound
related problems were analysed. RESULT: Ninety-seven patients underwent ALIF with
this new skin incision. One hundred fifty-seven levels were treated (mean 1.7
level per patient) being L4-L5 the most frequently treated. Intraoperative
complications were represented only by the venous injury with a rate of 3.09% (3
cases). Postoperative complications were all linked to skin incision issues: a
case of wound dehiscence and a case of superficial infection. No case of skin
necrosis occurs at 3-month follow-up. CONCLUSIONS: In this paper, the perinavel
skin incision was demonstrated to be as safe as traditional approaches for ALIF.
Furthermore, with this incision it is possible to perform multilevel (L3-S1)
ALIF, which means a good option in minimally invasive surgery as well as revision
surgery. These slides can be retrieved under Electronic Supplementary Material.
PMID- 29948322
TI - Time to augment?! Impact of cement augmentation on pedicle screw fixation
strength depending on bone mineral density.
AB - PURPOSE: Cement augmentation of pedicle screws is known to increase their
mechanical strength. Aim was to evaluate the impact of cement augmentation on
pedicle screw fatigue strength in dependence of the bone mineral density (BMD).
METHODS: Twenty-one human L2 vertebral bodies from donors between 19 and 96 years
of age were used for in vitro experiments. BMD was measured using quantitative
computed tomography (QCT). Two pedicle screws were inserted in each specimen and
unilaterally augmented with bone cement. Fatigue testing was performed using a
cranio-caudal sinusoidal, cyclic load (0.5 Hz) with increasing compression force
(100 N + 0.1 N/cycles). Results were evaluated for the BMD groups: normal: BMD >
120 mg/cm3, osteopenic: BMD 80-120 mg/cm3, and osteoporotic: BMD < 80 mg/cm3 bone
mass. RESULTS: There was a significant correlation between fatigue force and BMD
for the non-augmented and augmented screws (non-augmented R2 = 0.839, p < 0.001;
augmented R2 = 0.551, p < 0.001). There was a significantly increased fatigue
strength of the augmented screws over the non-augmented screws in the
osteoporotic group (p = 0.001), while the differences in the other groups were
not significant (normal p = 0.818/osteopenic p = 0.132). CONCLUSIONS: The benefit
of pedicle screw cement augmentation significantly depends on the bone mineral
density and has the greatest extent of increased fatigue strength in osteoporotic
vertebrae. Preoperative measurement of the BMD is strongly recommended to predict
the benefit of augmentation and reinforce the decision for cement augmentation.
These slides can be retrieved under Electronic Supplementary Material.
PMID- 29948323
TI - Expert's Comment concerning Grand Rounds case entitled "Chyluria and chylothorax
after posterior selective fusion for adolescent idiopathic scoliosis" by A.A.
Weening et al. Eur Spine J; DOI 10.1007/s00586-017-5066-y.
PMID- 29948325
TI - F-waves of peroneal and tibial nerves in the differential diagnosis and follow-up
evaluation of L5 and S1 radiculopathies.
AB - PURPOSE: To investigate F-wave as a method to identify a specific root lesion of
L5 or S1 and to quantitatively evaluate the severity and progression of motor
root lesions in lumbosacral radiculopathies (LR). METHODS: Both peroneal and
tibial F-waves were performed bilaterally in 142 patients with unilateral L5 or
S1 radiculopathies and 37 controls along with Medical Research Council (MRC)
evaluation, and soleus H-reflexes were tested bilaterally in 78 of these 142
cases. Both F-wave and MRC were re-evaluated approximately 1 year after initial
examination in 65 patients. RESULTS: Abnormal peroneal F-waves were found in 34
patients with L5 radiculopathy (34/67, 50.7%) along with normal tibial F-waves
and soleus H-reflexes in all tested cases. By contrast, 27 patients with S1
radiculopathy presented abnormal tibial F-waves (27/76, 36.0%) along with normal
peroneal F-waves in all 76 cases and abnormal soleus H-reflexes in 38 of 47
(80.9%) cases. There were significant differences in involved side F-duration
among different MRC scales in both radiculopathy groups (P < 0.05). Follow-up
analysis demonstrated slow progression of both F-wave abnormalities and muscle
weakness in patients undergoing conservative treatment (P < 0.05). CONCLUSIONS:
Comparisons of F-waves between the same nerve on both sides and between peroneal
and tibial nerves in the same leg may clearly increase the validity of F-waves
for evaluating a specific motor root lesion of L5 or S1. Furthermore, a
quantitative comparison of F-waves may provide additional information on the
severity of individual root lesions and their progression even in the early
stages of disease. These slides can be retrieved under Electronic Supplementary
Material.
PMID- 29948324
TI - Bilateral vocal cord palsy after a posterior cervical laminoplasty.
AB - PURPOSE: To report a patient with bilateral vocal cord palsy following cervical
laminoplasty, who survived following a tracheotomy and intensive respiratory
care. METHODS: Acute respiratory distress is a fatal complication of cervical
spinal surgery. The incidence of bilateral vocal cord palsy after posterior
cervical decompression surgery is extremely rare. The authors report a 71-year
old woman who suffered from cervical myelopathy due to ossification of the
posterior longitudinal ligament. Open-door laminoplasty from C2 to C6 and
laminectomy of C1 were performed. Following surgery, extubation was successfully
conducted. Acute-onset dysphagia and stridor had occurred 2 h following
extubation. A postoperative fiber optic laryngoscope revealed bilateral vocal
cord palsy. After a tracheotomy and intensive respiratory care, she had
completely recovered 2 months after surgery. DISCUSSION: One potential cause of
this pathology was an intraoperative hyper-flexed neck position, which likely
induced mechanical impingement of the larynx, resulting in swelling and edema of
the vocal cords and recurrent laryngeal nerve paresis. Direct trauma of the vocal
cords during intubation and extubation could have also induced vocal cord
paralysis. CONCLUSIONS: We reported a case of bilateral vocal cord palsy
associated with posterior cervical laminoplasty. Airway complications following
posterior spinal surgery are rare, but they do occur; therefore, spine surgeons
should be aware of them and take necessary precautions against intraoperative
neck position, intubation technique, even positioning of the intratracheal tube.
PMID- 29948326
TI - In vitro investigation of two connector types for continuous rod construct to
extend lumbar spinal instrumentation.
AB - PURPOSE: Instrumentation of the lumbar spine is a common procedure for treating
pathologic conditions. Studies have revealed the risks of pathologies in the
adjacent segments, with the incidence rate being up to 36.1%. Revision procedures
are often required, including extension of the instrumentation by the use of
connectors to adjacent levels. The aim of this study was to determine the
stiffness of side-to-side and end-to-end connectors for comparison with the use
of continuous rods. METHODS: Ten human lumbar spine specimens (L1-S1) were tested
about the three axes under pure moment loading of +/- 7.5 Nm. Nine conditions
were used to investigate the functions of the extensions for different
instrumentation lengths (L3-S1 and L2-S1) and different connector levels (L3/4
and L2/3). The intersegmental range of motion (iROM) and intersegmental neutral
zone as well as total range of motion (tROM) and total neutral zone (tNZ) were
analyzed. RESULTS: The application of the spinal system significantly decreased
the tROMs (- 44 to - 83%) and iROMs in levels L2/3 (- 56 to - 94%) and L3/4 (- 68
to - 99%) in all the tested directions, and the tNZ under flexion/extension (- 63
to - 71%) and axial rotation (- 34 to - 72%). These decreases were independent of
the employed configuration (p < 0.05). The only significant changes in the iROM
were observed under lateral bending between the continuous rod and the side-to
side connector at level L3/4 (p = 0.006). CONCLUSION: From a biomechanical
viewpoint, the tested connectors are comparable to continuous rods in terms of
ROM and NZ. These slides can be retrieved under Electronic Supplementary
Material.
PMID- 29948327
TI - Macrophage polarization contributes to local inflammation and structural change
in the multifidus muscle after intervertebral disc injury.
AB - PURPOSE: Intervertebral disk (IVD) lesion and its subsequent degeneration have a
profound effect on the multifidus muscle. The subacute/early chronic phase of
multifidus remodeling after IVD lesion has been proposed to be regulated by
inflammatory processes. The balance between pro-inflammatory (M1) and anti
inflammatory (M2) macrophages plays an important role in maintaining tissue
integrity after injury. The localization, polarization of macrophage subtypes and
their mediation of the pro-inflammatory cytokine tumor necrosis factor (TNF) are
unknown in paraspinal muscles during IVD degeneration. A sheep model of IVD
degeneration was used to investigate the role of macrophages and TNF in the
structural alterations that occur within the multifidus muscle. METHODS:
Anterolateral lesions were induced at L3-4 IVD in sheep. Multifidus muscle tissue
at L4 was harvested 3 and 6 months after lesion and used for immunofluorescence
assays to examine total macrophage number, macrophage polarization between M1 and
M2, and to assess the localization of TNF expression in muscle, adipose and
connective tissues from injured and naive control animals. RESULTS: A greater
proportion of M1 macrophages is present in muscle at both 3 and 6 months after
IVD lesion, and adipose tissue at 6 months. Total number of macrophages is
unchanged. At 6 months, expression of TNF is increased in adipose and connective
tissue and the proportion of TNF expressed by M1 macrophages is increased.
CONCLUSIONS: These data support the proposal that macrophages and TNF (pro
inflammatory cytokine) play an active role in the subacute/early chronic phase of
remodeling in muscle, adipose and connective tissues of the multifidus during IVD
degeneration. This presents a novel target for treatment. These slides can be
retrieved under Electronic Supplementary Material.
PMID- 29948329
TI - Whole mitochondrial genome diversity in two Hungarian populations.
AB - Complete mitochondrial genomics is an effective tool for studying the demographic
history of human populations, but there is still a deficit of mitogenomic data in
European populations. In this paper, we present results of study of variability
of 80 complete mitochondrial genomes in two Hungarian populations from eastern
part of Hungary (Szeged and Debrecen areas). The genetic diversity of Hungarian
mitogenomes is remarkably high, reaching 99.9% in a combined sample. According to
the analysis of molecular variance (AMOVA), European populations showed a low,
but statistically significant level of between-population differentiation (Fst =
0.61%, p = 0), and two Hungarian populations demonstrate lack of between
population differences. Phylogeographic analysis allowed us to identify 71
different mtDNA sub-clades in Hungarians, sixteen of which are novel. Analysis of
ancestry-informative mtDNA sub-clades revealed a complex genetic structure
associated with the genetic impact of populations from different parts of
Eurasia, though the contribution from European populations is the most
pronounced. At least 8% of ancestry-informative haplotypes found in Hungarians
demonstrate similarity with East and West Slavic populations (sub-clades H1c23a,
H2a1c1, J2b1a6, T2b25a1, U4a2e, K1c1j, and I1a1c), while the influence of
Siberian populations is not so noticeable (sub-clades A12a, C4a1a, and probably
U4b1a4).
PMID- 29948328
TI - Stress, inflammation, and eicosanoids: an emerging perspective.
AB - Clinical and experimental studies support the notion that adrenergic stimulation
and chronic stress affect inflammation, metabolism, and tumor growth. Eicosanoids
are also known to heavily influence inflammation while regulating certain stress
responses. However, additional work is needed to understand the full extent of
interactions between the stress-related pathways and eicosanoids. Here, we review
the potential influences that stress, inflammation, and metabolic pathways have
on each other, in the context of eicosanoids. Understanding the intricacies of
such interactions could provide insights on how systemic metabolic effects
mediated by the stress pathways can be translated into therapies for cancer and
other diseases.
PMID- 29948330
TI - MiR-195 suppresses colon cancer proliferation and metastasis by targeting WNT3A.
AB - MicroRNAs (miRNAs) are a novel class of diagnostic and therapeutic target in
cancer. Here, we aimed to explore the effects and mechanism of miR-195 regulation
in colon cancer. The expressions of several putative miRNAs in colon tumors,
compared to those in normal tissues, were investigated by bioinformatical
analysis of a Gene Expression Omnibus database. Quantitative real-time PCR
analysis (qRT-PCR) was used to validate the identified changes in normal tissues,
primary tumors, and metastatic tumors. MTT, soft agar colony formation, and
transwell assays were used to evaluate the effects of miR-195 overexpression or
inhibition on cell viability, proliferation, migration, and invasion. Targets of
miR-195 were identified by TargetScan, and subsequently verified by qRT-PCR and
Western blot. The role of miR-195 in the beta-catenin pathway was also studied
using RT-PCR and Western blot. MiR-195 expression was downregulated in colon
carcinoma tissues and negatively correlated with the metastatic potential. While
transfecting miR-195 mimics decreased the proliferation, migration, and invasion
of colon cancer cells, miR-195 inhibition exerted opposing effects. WNT3A was
identified as a direct target of miR-195. beta-catenin was also downregulated by
miR-195 in colon cancers. MiR-195 downregulation is associated with the enhanced
proliferation, migration, and invasion of colon cancer. MiR-195 directly
downregulates WNT3A. Our results indicate that miR-195 is a potential diagnostic
marker and therapeutic target for improving the clinical management of colon
cancer.
PMID- 29948331
TI - Whole-exome sequencing in maya indigenous families: variant in PPP1R3A is
associated with type 2 diabetes.
AB - It has been presumed that increased susceptibility in Mexicans to type 2 diabetes
(T2D) is attributed to the Native American genetic ancestry. Nonetheless, it is
not known if there are private genetic variants that confer susceptibility to
develop T2D in our population. The Maya indigenous group has the highest
proportion of Native American ancestry (98%) which makes it a representative
group of the original peoples of Mexico. Thus, the aim of the present study is to
identify new genetic variants associated with T2D in Maya families. Whole-exome
sequencing was performed on DNA samples from Maya families with a third
generation family history of T2D only in one parental line. Four variants were
identified for APOB, PPP1R3A, TPPP2, and GPR1 genes, and were further tested for
association with T2D in 600 unrelated Maya in a case-control study. For the first
time, rs1799999 in PPP1R3A was associated with risk of T2D in Mayan Mexican
individuals (OR = 1.625, P = 0.014). Interestingly, carriers of rs1799999
presented increased values of HOMA-IR. In addition, rs1801702 in APOB was
associated with total cholesterol and LDL-C (P = 0.019 and P = 0.020,
respectively) in normoglycemic individuals; rs3732083 in GPR1 with HOMA-IR (P =
0.016) and rs9624 in TPPP2 with total cholesterol and triglycerides (P = 0.002
and P = 0.005, respectively) in T2D subjects. Overall, these findings support the
idea that there are other genetic variants yet to be described, involved in T2D
development in Maya population, being insulin resistance and lipid metabolism the
main mechanisms implicated. Thus, these results can contribute to the
understanding of diabetes genetic background in Mexican population.
PMID- 29948333
TI - Food Insecurity, Internalized Stigma, and Depressive Symptoms Among Women Living
with HIV in the United States.
AB - Food insecurity, internalized HIV stigma, and depressive symptoms are
independently associated with poor HIV outcomes. Food insecurity, stigma, and
depression may be interrelated among women living with HIV (WLHIV). We
hypothesized that food insecurity would be independently associated with
internalized stigma and depressive symptoms among WLHIV in the United States
(US), and would partially account for associations between stigma and depressive
symptoms. We tested hypotheses using regression models and partial correlation
analysis with cross-sectional data among 1317 WLHIV from the Women's Interagency
HIV Study. In adjusted models, greater food insecurity was associated with
internalized HIV stigma and depressive symptoms (all p < 0.05), exhibiting dose
response relationships. Food insecurity accounted for 23.2% of the total shared
variance between depressive symptoms and internalized stigma. Food insecurity is
associated with depressive symptoms and internalized HIV stigma among US WLHIV,
and may play a role in the negative cycle of depression and internalized stigma.
PMID- 29948332
TI - Analyses of the genetic diversity and protein expression variation of the acyl:
CoA medium-chain ligases, ACSM2A and ACSM2B.
AB - Benzoate (found in milk and widely used as preservative), salicylate (present in
fruits and the active component of aspirin), dietary polyphenols produced by gut
microbiota, metabolites from organic acidemias, and medium-chain fatty acids
(MCFAs) are all metabolised/detoxified by the glycine conjugation pathway.
Xenobiotics are first activated to an acyl-CoA by the mitochondrial
xenobiotic/medium-chain fatty acid: CoA ligases (ACSMs) and subsequently
conjugated to glycine by glycine N-acyltransferase (GLYAT). The MCFAs are
activated to acyl-CoA by the ACSMs before entering mitochondrial beta-oxidation.
This two-step enzymatic pathway has, however, not been thoroughly investigated
and the biggest gap in the literature remains the fact that studies continuously
characterise the pathway as a one-step reaction. There are no studies available
on the interaction/competition of the various substrates involved in the pathway,
whilst very little research has been done on the ACSM ligases. To identify
variants/haplotypes that should be characterised in future detoxification
association studies, this study assessed the naturally observed sequence
diversity and protein expression variation of ACSM2A and ACSM2B. The allelic
variation, haplotype diversity, Tajima's D values, and phylogenetic analyses
indicated that ACSM2A and ACSM2B are highly conserved. This confirmed an earlier
hypothesis that the glycine conjugation pathway is highly conserved and essential
for life as it maintains the CoA and glycine homeostasis in the liver
mitochondria. The protein expression analyses showed that ACSM2A is the
predominant transcript in liver. Future studies should investigate the effect of
the variants identified in this study on the substrate specificity of these
proteins.
PMID- 29948335
TI - Preferences for Sexual Health Smartphone App Features Among Gay and Bisexual Men.
AB - Given the popularity of geosocial networking applications ("apps") among gay,
bisexual, and other men who have sex with men (GBMSM), this study sought to
examine GBMSM's willingness to use sexual health and behavior tracking features
if integrated within apps they are already using to meet sexual partners. Most
GBMSM (91%) recruited on a popular app reported interest in one or more sexual
health app features, including features to find LGBT-friendly providers (83%),
receive lab results (68%), schedule appointment reminders (67%), chat with a
healthcare provider (59%), and receive medication reminder alerts (42%). Fewer
GBMSM were interested in tracking and receiving feedback on their sexual behavior
(35%) and substance use (24%). Our data suggest that integrating sexual health
and behavior tracking features for GBMSM who use apps could be promising in
engaging them in HIV prevention interventions. Further research is needed on
GBMSM's perspectives about potential barriers in using such features.
PMID- 29948334
TI - A Critical Review and Commentary on the Challenges in Engaging HIV-Infected
Latinos in the Continuum of HIV Care.
AB - Antiretroviral therapy for treatment of HIV infection has become increasingly
effective. Persistent poor HIV outcomes in racial and ethnic minority populations
in the US call for a closer examination into why Latinos are at significant risk
for acquiring and dying from HIV. To improve clinical outcomes and achieve an
AIDS-free generation, HIV research must address disparities in HIV outcomes in
Latinos, the largest ethnic/racial minority population in the US. Immigrant
status as well as cultural factors influence HIV care utilization and are
essential to highlight for effective intervention development in Latinos. A
better understanding of these individual and contextual factors is critical to
developing tailored approaches to engaging Latinos in HIV care. Based on a
comprehensive literature review, we offer a framework for understanding what is
needed from clinical practice and research to improve engagement in HIV care for
US-based Latinos. These findings may have implications for other minority
populations.
PMID- 29948337
TI - Impact of a Rapid Results Initiative Approach on Improving Male Partner
Involvement in Prevention of Mother to Child Transmission of HIV in Western
Kenya.
AB - A rapid results initiative (RRI) aimed at increasing male involvement in
prevention of mother-to-child transmission (PMTCT) and service uptake among
pregnant women at 116 antenatal clinics in Western Kenya was compared at
baseline, during the RRI, and 3-months post-RRI. Male involvement increased from
7.4 to 54.2% during RRI (risk difference [RD] 0.47, CI 0.45-0.48) then 43.4% post
RRI (RD 0.36, CI 0.35-0.37). Among HIV-infected women, facility delivery
increased from 40.0 to 49.9% (RD 0.10, 95% CI 0.06-0.13) and 65.0% post-RRI (RD
0.25, 95% CI 0.22-0.28). HIV-infected pregnant women linkage to HIV care
increased from 58.6 to 85.9% (RD 0.27, CI 0.24-0.30) and 97.3% post-RRI (RD 0.39,
CI 0.36-0.41). Time to ART initiation reduced from 29 days (interquartile range
[IQR] 6-56) to 14 days (IQR 0-28) to 7 days (IQR 0-20). A male-centered RRI can
significantly increase men's engagement in antenatal care leading to improved
partner utilization of PMTCT and antenatal services.
PMID- 29948336
TI - Intimate Partner Violence and HIV Sexual Risk Behaviour Among Women Who Inject
Drugs in Indonesia: A Respondent-Driven Sampling Study.
AB - Women who inject drugs are disproportionately affected by HIV and intimate
partner violence (IPV); however, the link between IPV and HIV remains under
researched among substance-using women in low- and middle-income countries. This
study examined associations and additive effects of different forms of IPV
victimization (psychological, physical and/or injurious, and sexual) on HIV
sexual risk behavior among women who inject drugs in Indonesia. Respondent-driven
sampling (RDS) was used to recruit 731 women from Greater Jakarta and Bandung,
West Java. RDS-II weighted prevalence of any past-year IPV was 68.9% (95% CI
65.0, 72.6) in Jakarta and 55.9% (95% CI 48.0, 63.5) in Bandung. In separate
logistic regressions controlling for socio-demographic covariates, all three
forms of IPV showed statistically significant associations with sexual risk
behavior. After adjusting for all IPV types, psychological (OR 1.87; 95% CI 1.17,
2.99; p = 0.009) and sexual (OR 1.98; 95% CI 1.22, 3.21; p = 0.006) IPV
independently predicted women's sexual risk behavior. Marginal effects models
suggested that co-occurrence of multiple forms of IPV had greater adverse
consequences: sexual risk behavior was reported by 64.1% of women who did not
experience any IPV, but increased to 89.9% among women exposed to all three
types. Comprehensive harm reduction services that integrate IPV monitoring and
prevention are urgently needed to reduce both HIV and IPV.
PMID- 29948338
TI - Stigmatizing Attitudes Toward People Living with HIV Among Adults and Adolescents
in the United States.
AB - Stigmatizing attitudes toward people living with HIV (PLWH) cause psychological
distress for PLWH and hinder HIV prevention efforts. We estimated the prevalence
of stigmatizing attitudes among 6809 adults and 885 adolescents who responded to
online surveys in 2015. Fear of casual contact with PLWH was reported by 17.5%
[95% confidence interval (CI) 16.3-18.6%] of adults and 31.6% (CI 27.8-35.4%) of
adolescents. Among adults, 12.5% (CI 11.6-13.5%) endorsed a measure of moral
judgment toward PLWH. Stigmatizing attitudes toward PLWH persist in the United
States. Continued monitoring of these attitudes and efforts to reduce associated
stigma are warranted.
PMID- 29948339
TI - The Impact of Cell Phone Support on Psychosocial Outcomes for Youth Living with
HIV Nonadherent to Antiretroviral Therapy.
AB - Mobile health interventions to promote adherence to antiretroviral therapy among
adolescents and young adults living with HIV represent a promising strategy. This
pilot study (N = 37) evaluated the psychosocial impacts of an efficacious
adherence intervention, cell phone support (CPS). Participants receiving CPS
reported significant decreases in perceived stress, depression, and illicit
substance use, and increases in self-efficacy during at least one study
assessment period, in comparison to participants receiving usual care. Future
research using a larger sample should test for mediators of treatment efficacy to
further characterize how cell phone interventions impact adherence.
PMID- 29948340
TI - National Trends in Sexual Behavior, Substance Use and HIV Testing Among United
States Men Who have Sex with Men Recruited Online, 2013 Through 2017.
AB - The American Men's Internet Survey (AMIS) is conducted annually with 10,000 men
age 15 + who have sex with men (MSM). Modeling was used with 39,863 AMIS surveys
from 4 cycles between December 2013 to February 2017 to identify temporal trends
in sexual behavior, substance use, and testing behavior (within 12 months
preceding interview) stratified by participants' self-reported HIV status. HIV
negative/unknown status MSM had significant increases in condomless anal
intercourse (CAI), marijuana use, use of other illicit substances, sexually
transmitted infection (STI) diagnoses, and HIV or STI testing (testing only
increased among MSM age 25 +). HIV-negative/unknown status MSM had significant
decrease in CAI with an HIV-positive or unknown status partner. HIV-positive MSM
had significant increases in CAI, methamphetamine use, and STI diagnoses/testing.
Although encouraging, the few indicators of improvement in HIV/STI sexual health
practices are not consistently seen across sub-groups of MSM and may be
counteracted by growing proportions of MSM engaging in CAI and acquiring STIs.
PMID- 29948341
TI - Risk Behaviors and Perceptions Among Self-identified Men Who Have Sex with Men
(MSM), Bisexuals, Transvestites, and Transgender Women in Western Guatemala.
AB - Guatemala has a concentrated HIV epidemic disproportionately affecting men who
have sex with men (MSM) and transgender women. We recruited 205 self-identified
MSM, bisexuals, transvestites, and transgender women in western Guatemala using
long-chain peer referral, wherein "seed" participants were asked to invite as
many as three acquaintances to participate in the study. Self-reported sexual or
gender identity was MSM, 46%; bisexual, 28%; transvestite, 21%, and transgender
woman, 5%. Median age of the participants was 23 years, and 36% self-identified
as being indigenous. Indigenous persons were more likely to self-identity as
transvestite (32.9% vs 13.8%, P = 0.04), strongly perceive themselves at risk for
HIV (87.7% vs 51.5%, P = 0.001), have had an HIV test in the last 12 months and
know the result (97.3% vs 85.4%, P = 0.008), and experience barriers to testing
and treatment (86.3% vs 67.7%, P = 0.004). HIV prevention services for indigenous
MSM should especially target transvestites and how to overcome stigmatization and
barriers to care.
PMID- 29948342
TI - Antimicrobial and structural insights of a new snakin-like peptide isolated from
Peltophorum dubium (Fabaceae).
AB - Snakins are antimicrobial peptides (AMPs) found, so far, exclusively in plants,
and known to be important in the defense against a wide range of pathogens. Like
other plant AMPs, they contain several positively charged amino acids, and an
even number of cysteine residues forming disulfide bridges which are considered
important for their usual function. Despite its importance, studies on snakin
tertiary structure and mode of action are still scarce. In this study, a new
snakin-like gene was isolated from the native plant Peltophorum dubium, and its
expression was verified in seedlings and adult leaves. The deduced peptide
(PdSN1) shows 84% sequence identity with potato snakin-1 mature peptide, with the
12 cysteines characteristic from this peptide family at the GASA domain. The
mature PdSN1 coding sequence was successfully expressed in Escherichia coli. The
purified recombinant peptide inhibits the growth of important plant and human
pathogens, like the economically relevant potato pathogen Streptomyces scabies
and the opportunistic fungi Candida albicans and Aspergillus niger. Finally,
homology and ab initio modeling techniques coupled to extensive molecular
dynamics simulations were used to gain insight on the 3D structure of PdSN1,
which exhibited a helix-turn-helix motif conserved in both native and recombinant
peptides. We found this motif to be strongly coded in the sequence of PdSN1, as
it is stable under different patterns of disulfide bonds connectivity, and even
when the 12 cysteines are considered in their reduced form, explaining the
previous experimental evidences.
PMID- 29948343
TI - The unique tRNASec and its role in selenocysteine biosynthesis.
AB - Selenium (Se) is an essential trace element for several organisms and is mostly
present in proteins as L-selenocysteine (Sec or U). Sec is synthesized on its L
seryl-tRNASec to produce Sec-tRNASec molecules by a dedicated selenocysteine
synthesis machinery and incorporated into selenoproteins at specified in-frame
UGA codons. UGA-Sec insertion is signaled by an mRNA stem-loop structure called
the SElenoCysteine Insertion Sequence (SECIS). tRNASec transcription regulation
and folding have been described showing its importance to Sec biosynthesis. Here,
we discuss structural aspects of Sec-tRNASec and its role in Sec biosynthesis as
well as Sec incorporation into selenoproteins. Defects in the Sec biosynthesis or
incorporation pathway have been correlated with pathological conditions.
PMID- 29948344
TI - Hepatosplenomegaly, pneumopathy, bone changes and fronto-temporal dementia:
Niemann-Pick type B and SQSTM1-associated Paget's disease in the same individual.
AB - Data from exome sequencing show that a proportion of individuals in whom a
genetic disorder is suspected turn out to have not one, but two to four distinct
ones. This may require an evolution in our diagnostic attitude towards
individuals with complex disorders. We report a patient with splenomegaly,
pneumopathy, bone changes and fronto-temporal dementia (FTD). "Sea-blue
histiocytes" in his bone marrow pointed to a lysosomal storage disease.
Homozygosity for a pathogenic mutation in the SMPD1 gene confirmed Niemann-Pick
disease type B (NPD-B). Mild cognitive impairment and abnormal brain FDG PET were
consistent with FTD. We initially tried to fit the skeletal and neurologic
phenotype into the NPD-B diagnosis. However, additional studies revealed a
pathogenic mutation in the SQSTM1 gene. Thus, our patient had two distinct
diseases; NPD-B, and Paget's disease of bone with FTD. The subsequent finding of
a mutation in SQSTM1 gene ended our struggle to explain the combination of
findings by a singular "unifying" diagnosis and allowed us to make specific
therapeutic decisions. SQSTM1 mutations have been reported in association with
FTD, possibly because of defective autophagy. Bisphosphonates may be beneficial
for PDB, but since they are known to inhibit acid sphingomyelinase activity, we
refrained from using them in this patient. While the principle of looking for
unifying diagnosis remains valid, physicians should consider the possibility of
co-existing multiple diagnoses when clinical features are difficult to explain by
a single one. Accurate diagnostic work-up can guide genetic counseling but also
lead to better medical management.
PMID- 29948345
TI - Low serum 25-hydroxyvitamin D increases cognitive impairment in elderly people.
AB - It has been reported that many elderly people have low serum levels of 25
hydroxyvitamin D [25(OH)D] and that serum 25(OH)D levels may have a relationship
with cognitive function. The aim of this study was to examine the relationship
between serum 25(OH)D levels and cognitive function in a Japanese population.
This cross-sectional study was performed as a part of the Project in Sado for
Total Health (PROST). The PROST study evaluated cognitive state and serum vitamin
D level from June 2011 to November 2013 for 740 patients (431 men and 309 women).
The Mini-Mental State Examination-Japanese version (MMSE-J) and serum 25(OH)D
level measurements were used as assessment tools. Cognitive impairment was
defined using MMSE-J <= 23 as a cutoff. Multiple logistic regression analyses
were performed to calculate the odds ratios (ORs) for low MMSE-J scores. The
average subject age was 68.1 years, the average MMSE- J score was 25.9, and the
average 25(OH)D level was 24.6 ng/mL. Significant ORs for cognitive impairment
were observed for both high age and low serum 25(OH)D. The adjusted OR for the
lowest versus highest serum 25(OH)D quartiles was 2.70 (95% confidence interval
1.38-5.28, P = 0.0110). Low serum 25(OH)D levels were independently associated
with a higher prevalence of cognitive impairment.
PMID- 29948346
TI - Association between the -174 C/G polymorphism in the interleukin-6 (IL-6) gene
and gastrointestinal involvement in patients with systemic sclerosis.
AB - Genetic predisposition to systemic sclerosis (SSc) has still not been fully
revealed. Interleukin-6 (IL-6) is a mediator of T cell proliferation and fibrotic
events in SSc. Polymorphisms in the IL-6 are found to be important in
susceptibility to development of SSc. We aimed to assess the frequency of -174
C/G of IL-6 gene polymorphism in SSc patients and healthy controls, as well as
correlation with disease manifestations. In the case-control study, 102 patients
with SSc and 93 controls were included. PCR-RFLP method was performed for
genotyping promotor variants -174 C/G of IL-6 gene. The expression level of IL-6
was determined by qRT-PCR on subset of 50 patients and 13 healthy controls with
different IL-6 genotypes. We used UCLA GIT 2.0 questionnaire to assess
gastrointestinal involvement in SSc patients. The expression level of IL-6 gene
was significantly higher in patients with SSc in comparison with healthy controls
(p < 0.05). Carriers of C-allele of IL-6 gene compared to those with G allele,
showed higher expression of IL-6 gene (95.8 vs. 41.2, p < 0.05), higher GIT total
score (0.85 vs. 0.5, p < 0.05) and higher distension scale score (1.4 +/- 0.9 vs.
0.78 +/- 0.8, p = 0.05). No significant differences in genotype distribution and
allele frequency were observed between patients and controls. The expression of
IL6 gene varies significantly during the course of SSc. The IL-6 gene variant
174 C/G (presence of C-allele) is associated with higher IL-6 gene expression and
greater GIT impairment in patients with SSc.
PMID- 29948347
TI - Disease and management beliefs of elderly patients with rheumatoid arthritis and
comorbidity: a qualitative study.
AB - To explore in elderly patients with rheumatoid arthritis (RA) and comorbidity (1)
in which order and why patients prioritize their morbidities with regard to
functioning and health, (2) their beliefs about common (age-related)
musculoskeletal complaints, and (3) experiences about the influence of
comorbidity on medication treatment of RA. Patients between 50 and 85 years with
RA and >= 1 comorbidity or lifestyle risk factor were invited for a semi
structured interview. Two readers coded the transcripts of the interviews, by
using NVivo11 software. Fifteen patients (14 women; mean age 67 years (range 51
83 years); mean disease duration 14 years (range 1-39 years)) were interviewed.
Only 3 (20%) out of 15 patients prioritized RA over their comorbidity; these
patients often experienced severe functional limitations. The level of current or
(perceived) future disability, risk of dependency, and the perceived lethality of
a condition were considered by participants when prioritizing morbidities. Most
participants had misconceptions about common age-related musculoskeletal
complaints. Consequently, these participants attributed all joint complaints or
even all physical complaints to RA, disregarding degenerative joint disease and
physiological aging as alternative diagnoses. Half of the participants ever had
to change RA medication because of comorbidity. Most of these patients had
prioritized the comorbidity, sometimes even over treatment of RA disease
activity. Most elderly RA patients with comorbidity prioritize the importance and
treatment of comorbidity over RA. Better understanding of patients' beliefs on RA
and comorbidity is essential when managing chronic conditions in elderly
patients.
PMID- 29948348
TI - Anti-annexin A5 antibodies and 25-hydroxy-cholecalciferol in female patients with
primary antiphospholipid syndrome.
AB - Vascular antiphospholipid syndrome (VAPS) and obstetric (OAPS) are different
entities because some patients only develop thrombosis (without recurrent
pregnancy losses) and vice versa. Only two articles have reported that low 25
hydroxy-cholecalciferol (vitamin D3, VD3) levels were not correlated with the
presence of conventional antiphospholipid antibodies (aPL Abs: anticardiolipin
(aCL), anti-beta2glycoprotein I (abeta2gpI), and lupus anticoagulant (LA)), but
no article analyzed the association of VD3 and anti-annexin A5 (aanxA5) Abs. The
aim of our study was to investigate the association between VD3, multiple
positivity of conventional aPL and aanxA5 Abs levels only in female OAPS vs.
VAPS. Our study included 62 consecutive female PAPS patients. Concentrations of
Abs were measured by ELISA, while VD3 levels were determined by
immunochemiluminescence. Only 10/62 (16.13%) had sufficient (>= 30 ng/ml) VD3
levels, while 48/62 (77.42%) and 4/62 (6.45%) had insufficiency and VD3
deficiency, respectively. Statistically significant VD3 deficiency was noticed in
VAPS (vs. OAPS, P = 0.013). A negative correlation between VD3 levels and the age
of patients was noticed (r = - 0.493, P = 0.032) only in VAPS subgroup. Multiple
positivity of aPL and aanxA5 Abs was not associated with VD3 deficiency. Newly
emerging aPL Abs, such as aanxA5 Abs, or their combinations with classical aPL
Abs are not associated with VD3 deficiency in neither OAPS nor VAPS patients. Due
to its immunomodulatory roles in B-Ly homeostasis, supplementation with VD3
should be considered in APS, at least in subgroup with severe form of the
disease, i.e., VAPS.
PMID- 29948349
TI - Recognition and control of hypertension, diabetes, and dyslipidemia in patients
with systemic lupus erythematosus.
AB - Systemic lupus erythematosus (SLE) patients have a high risk for cardiovascular
events, but few studies have evaluated the recognition and none have evaluated
the control of cardiovascular risk factors (RF) in SLE patients. The study aims
to describe the recognition and control frequencies of systemic arterial
hypertension (SAH), dyslipidemia, and diabetes mellitus (DM) in SLE patients. Of
the female patients with SLE, 137 answered a questionnaire focused on general
knowledge of the RF for coronary artery disease (CAD) and on recognition of the
risk factors that they possess. The patient's information collected on a
structured medical record was reviewed to evaluate the RF control. The mean age
was 29.1 (9.6) years. Seventy patients had SAH; 85.7% recognized their condition
and 71.4% had desirable blood pressure (BP) control (< 140 * 90 mmHg). From a
group of 63 patients with dyslipidemia, 68.3% recognized that they had
dyslipidemia and 69.8% had desirable LDL-cholesterol (< 130 mg/dL). Sixteen
patients had DM; 87.5% admitted being diabetic and 50.0% had desirable glycemic
control (HbA1C < 7%). Most patients were aware of presenting SAH, DM, or
dyslipidemia, and the recognition frequency was higher in comparison to general
population. The SAH and dyslipidemia control frequencies were higher than that
described for the general population.
PMID- 29948350
TI - Socio-economic gradients in the presence of musculoskeletal and other chronic
diseases: results from a cross-sectional study in the Netherlands.
AB - Socio-economic gradients in occurrence of diseases have been reported for many
chronic conditions. However, whether the magnitude of socio-economic gradients
differs across diseases and the extent to which lifestyle mediates such
relationships are not known. Cross-sectional data from The National Monitor on
Musculoskeletal System was used. Respondents (> 18 years) completed a
questionnaire including gender, education, social status, lifestyle, and
physician-diagnosed diseases. Logistic regressions investigated the relationship
between education and the major chronic diseases (musculoskeletal diseases
(MSKD), diabetes, cardiovascular (CVD), cancer, mental, respiratory, any
disease). Next, analyses were repeated in individuals with potential to have paid
work (i.e., those < 65 having paid work, being unemployed, or receiving living
allowance (minimum income)). The mediating role of smoking and BMI between
education and occurrence of diseases was assessed by testing indirect effects.
From 8904 individuals (mean age 54 years, 46% male), 4378 (49%) had at least one
disease. Gradients in occurrence of disease by education were present for all
diseases except cancer and mental disease, with the strongest gradient in
diabetes (OR 2.0 [95%CI 1.4;2.8]). Unemployment and especially living on minimum
income were associated with increased odds to have MSKD and mental and
respiratory disease, after adjusting for education. Smoking and obesity mediated
part of the relationship between education and disease, with obesity playing more
pronounced role. Association between deprivation and occurrence of all major
chronic diseases is of comparable magnitude, with education having most
consistent contribution. Our results support the notion of the generic (i.e., non
disease specific) mechanisms underlying socio-economic gradients in health.
PMID- 29948351
TI - Development and application of a questionnaire to assess patient beliefs in
rheumatoid arthritis and axial spondyloarthritis.
AB - Misinterpretation of patient beliefs may complicate shared decision-making in
rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). The objective of
this study was to develop a questionnaire to assess patients' beliefs about their
disease and its treatment, and to identify patient characteristics associated
with these beliefs. All beliefs reported by > 5% of 50 patients in a previous
study were reformulated with a partnering patient organization into statements
with which participants could rate their agreement on a scale of 0-10 (totally
disagree to totally agree). The resulting Questionnaire for Arthritis Dialogue
(QuAD) was made available to patients with RA or axSpA. A score >= 7 was
considered a strongly held belief. Associations between patient characteristics
and individual lifestyle beliefs were assessed using multiple logistic
regression. The 21-item QuAD was completed by 672 patients (432 RA, 240 axSpA;
mean [+/-SD] age 54.2 [+/- 14.2]; 63.7% female). The most widely held beliefs
were related to uncertainty about progression (n = 354, 54.0%), heredity (n =
309, 47.8%), and flare triggers (n = 283, 42.7%). The unwarranted belief that
physical activity is deleterious to disease activity was associated with markers
of psychological distress and lower educational levels. The beliefs of patients
with RA or axSpA about their disease are wide-ranging. Since these may be
unwarranted and may lead to inappropriate behaviors, physicians should discuss
these beliefs with their patients. The QuAD may facilitate this dialogue, and may
also be useful in population studies to standardize the assessment and evolution
of beliefs over time. People with long-term inflammatory conditions such as
rheumatoid arthritis (RA; inflammation of the joints) and axial spondyloarthritis
(axSpA; inflammation of the spine) may hold a number of beliefs about their
disease, including some that are not supported by current scientific evidence
(e.g., "I think that my disease was triggered by a vaccination"). Some beliefs,
especially those relating to the role of lifestyle factors (such as exercise,
diet, smoking, and drinking alcohol), may encourage people living with severe
diseases to change their behavior in a way that has an effect on their disease.
Within this project, we developed a questionnaire to identify the most common
beliefs held by people living with RA or axSpA, which is called the
"Questionnaire for Arthritis Dialogue (QuAD)." We also examined whether certain
characteristics (or traits) of people living with RA or axSpA are linked to
beliefs not currently supported by scientific evidence. A total of 672 people
living with RA or axSpA in France were asked to complete the questionnaire
(QuAD). The questionnaire included 21 opinion statements that they scored from 0
(totally disagree) to 10 (totally agree). A score of more than 7 was interpreted
to mean that the person significantly agreed with the opinion. Based on the
responses to specific opinion statements in the questionnaire, we were able to
identify possible links between beliefs that are not supported by scientific
evidence (e.g., "I think that flare-ups of my disease are triggered by physical
effort"), and characteristics of people living with severe diseases. Our findings
suggested that beliefs about lifestyle and inflammatory diseases varied from
person to person, were sometimes inconsistent (the most widely held beliefs were
sometimes contradictory), and were often not supported by scientific evidence.
The belief that physical activity had negative effects on the disease was linked
to poor education and psychological issues (such as anxiety and helplessness).
People living with axSpA were more likely to believe their disease was a result
of their genetic make-up, whereas those with RA more often believed their disease
was caused by emotional issues. People living with axSpA were also more likely to
believe that physical activity could be beneficial for their disease, and less
likely to believe that their disease was caused by smoking. Our results suggest
that doctors need to discuss with their patients how they might believe lifestyle
is associated with their disease. This will help to dispel any unnecessary
concerns, and to encourage their patients to take up healthy lifestyles and
habits that are beneficial for their disease management. It may also be
beneficial for health care providers to discuss the beliefs identified in this
study during educational programs about inflammatory diseases, for the benefit of
people living with RA or axSpA.
PMID- 29948352
TI - Axial psoriatic arthritis: the impact of underdiagnosed disease on outcomes in
real life.
AB - Psoriatic arthritis (PsA) may affect different joints, including the spine. The
prevalence of spinal involvement is variable depending on the definition and a
subset of patients have been identified in cohorts that do not have clinical
features of axial disease and yet have imaging findings. Still, there is not a
consensus on how and when to screen axial disease. In this study, we aimed to
investigate factors associated with being underdiagnosed for axial psoriatic
arthritis (axPsA) and its impacts on outcomes. Disease features and outcomes of
axPsA according to the physician (n = 415) were compared with patients with
imaging findings only (sacroiliitis fulfilling the modified New York criteria, n
= 112), using data from a real-life PsA registry. Patients with imaging findings
only were more frequently women (83/220 (37.7%) vs 29/122 (23.8%); p = 0.008).
This group also had higher peripheral disease activity (imaging only vs clinical
AxPsA: mean (SD) tender joint count 5.3 (6.1) vs 3.3 (4.7), swollen joint count
1.9 (2.9) vs 1.2 (2.4); p < 0.001 for both comparisons) and was less often
treated using TNF inhibitors (16.1 vs 38.2%; p < 0.001) than patients who were
classified as axPsA. Patient-reported outcomes were similar in both groups. PsA
patients, especially women with more severe peripheral disease, have a higher
risk of being underdiagnosed for axPsA. The severity of peripheral symptoms may
be a risk factor to mask the spinal features of PsA.
PMID- 29948353
TI - Ultrasound-guided synovial biopsy improves diagnosis of septic arthritis in acute
arthritis without enough analyzable synovial fluid: a retrospective analysis of
176 arthritis from a French rheumatology department.
AB - To assess the diagnostic value of ultrasound-guided (US-guided) synovial biopsy
in routine clinical practice in cases of acute and chronic arthritis. A
retrospective, single-center study of US-guided synovial biopsies between 2003
and 2013. The clinical, laboratory, radiographic, synovial fluid, and
histological and bacteriological results of synovial biopsies were analyzed.
Arthritis was classified according to disease duration < 6 weeks (AA) or >= 6
weeks (CA). Synovial biopsy success rate was defined by the rate of capsular
and/or synovial tissue analyzed. The diagnostic efficiency was defined by
synovial biopsy success rate multiplied by the clinical utility (validation of a
diagnostic hypothesis leading to a specific therapy). One hundred seventy-six US
guided synovial biopsies (51 AA and 125 CA) were analyzed. Synovial biopsy
success rate was 82.4%. The diagnostic efficiency was 19.9%. Among the acute
arthritis cases, 11 were septic. Only three patients had a positive biopsy
culture while the synovial fluid puncture was of insufficient quantity to allow
bacteriological analysis. The perivascular infiltration of neutrophils (PMN) had
a sensitivity of 81.8%, a specificity of 84.2%, and a positive likelihood ratio
of 5.2 for the septic arthritis diagnosis. Among the chronic arthritis cases, no
case of pyogenic septic arthritis was found. No histological lesions, examined
separately, were specific to a type of chronic inflammatory joint disease. US
guided synovial biopsies remain relevant for the diagnosis of septic arthritis,
in cases of acute arthritis when joint aspiration is not possible.
PMID- 29948354
TI - Clinical characteristics of a concurrent condition of IgG4-RD and Castleman's
disease.
AB - IgG4-related disease (IgG4-RD) and Castleman's disease (CD) share similar
clinical manifestations. When the histopathology coincides with the diagnosis of
both IgG4-RD and CD, it is hard to depart the two disease entities utterly; here
we call it IgG4-CD provisionally. In this study, we aim to review the clinical
features of IgG4-CD. This study is based on a retrospective analysis of a
prospectively acquired database. IgG4-CD was defined histopathologically in
patients who fulfilled the diagnosis of both IgG4-RD and CD. Forty-five definite
IgG4-RD and 16 multicentric CD (MCD) patients were recruited as controls.
Clinical features including organ involvement, serum IgG4, IgG, IgE, ESR, CRP,
and IL-6 levels were collected and analyzed. Fifteen patients (2.8%) out of 534
patients with IgG4-RD in China's largest prospective IgG4-RD and Mimicry cohort
fulfilled the definition of IgG4-CD. There were 14 males and 1 female, whose mean
age was 47 +/- 18 years old, and the median disease duration before diagnosis was
12 (1-132) months. Eight patients have allergic disease history. IgG4-CD patients
had more lymph node involvement (100 vs 57.8%, P < 0.01), while IgG4-RD patients
had more submandibular (33.3 vs 77.1%, P < 0.01) and parotid gland (13.3 vs
40.9%, P < 0.05) affected. IgG4-CD patients had significantly higher levels of
ESR, CRP, IgG, IgG1, IgG3, IgG4, and IgE than IgG4-RD patients. Compared with MCD
patients, IgG4-CD patients showed higher incidence of salivary gland and
paranasal sinus involvement, higher hemoglobin, eosinophil count, serum IgG4
level and IgG4/IgG ratio, and lower CRP, IL-6 levels, and IgG1/IgG, IgG2/IgG
ratio. All patients with IgG4-CD exhibited relatively favorable outcomes. Both
IgG4-RD and CD can involve multiple organs. There are a small group of patients
who had clinical and pathological characteristics of both CD and IgG4-RD showed
better clinical outcome. In the long-term prognosis of these patients, the
relationship of CD and IgG4-RD is waiting to be further elucidated.
PMID- 29948355
TI - Comparison of splinting and Kinesio taping in the treatment of carpal tunnel
syndrome: a prospective randomized study.
AB - The aim of this study was to investigate and compare the effectiveness of
splinting and Kinesio taping (KT) as forms of treatment for patients with mild to
moderate idiopathic carpal tunnel syndrome (CTS) by evaluating the symptoms and
measuring the range of function and electrophysiological findings. This single
blind, randomized, prospective study included 44 patients (58 hands) suffering
mild to moderate idiopathic CTS according to nerve conduction studies (NCS). The
patients were randomized into two groups and evaluated before treatment and 6
weeks after treatment by means of physical examination findings, NCS, and the
Boston Carpal Tunnel Questionnaire (BCTQ) functional status and symptom severity
scale scores. When the differences in both groups before and after treatment were
compared, a significant improvement was observed in the KT group compared to the
splint group in terms of electrophysiological changes, provocative test
responses, BCTQ symptom severity, and functional status scores. KT may help
prevent the disease from progressing further in mild and moderate idiopathic CTS
when applied in time using the appropriate technique and be a good alternative to
neutral splinting in terms of patient compliance.
PMID- 29948356
TI - A phase Ib study of sonidegib (LDE225), an oral small molecule inhibitor of
smoothened or Hedgehog pathway, in combination with docetaxel in triple negative
advanced breast cancer patients: GEICAM/2012-12 (EDALINE) study.
AB - : Up-regulation of the Hedgehog (Hh) pathway is implicated in the genesis of a
wide range of tumors including triple negative breast cancer (TNBC). Sonidegib is
a potent and selective oral inhibitor of Smo, a key component of the Hh signaling
pathway. We designed a phase I clinical study to explore the combination of
sonidegib plus docetaxel (fixed dose at 75 mg/m2) in advanced TNBC patients. The
primary objective was to ascertain the combination's maximum tolerated dose and
the recommended phase II dose (RP2D), based on dose limiting toxicities (DLTs) in
the first 2 cycles. A standard "3 + 3" design was followed including three dose
levels (DL) of sonidegib: 400 mg (DL1), 600 mg (DL2), and 800 mg (DL3). Twelve
patients were included. Sonidegib 800 mg orally q.d. plus docetaxel 75 mg/m2
given intravenously on day 1 of 21-day cycles was established as the RP2D. No
DLTs were observed at any DL. The median number of administered cycles at DL3 was
8 (range: 6 to 9). Grade 3 adverse events (AEs) at DL3 were neutropenia (66.7%),
CPK increase (33.3%), leukopenia (33.3%), and paresthesia (33.3%), grade 4 AEs
were not reported at this DL. At the RP2D, the combination showed antitumor
activity in three out of 10 patients with measurable disease. Median time to
progression for the overall study was 42.5 days (95% Confidence Interval: 29
155), and 188 days at DL3. No drug-to-drug interactions between sonidegib and
docetaxel were found in the PK assessment. TRIAL REGISTRATION: EudraCT study
number: 2013-001750-96. Study GEICAM/2012-12. TRIAL REGISTRATION: EudraCT study
number: 2013-001750-96. Study GEICAM/2012-12. ClinicalTrials.gov: NCT02027376.
PMID- 29948357
TI - Phase II study of DFP-10917, a deoxycytidine analog, given by 14-day continuous
intravenous infusion for chemotherapy-refractory advanced colorectal cancer.
AB - Background DFP-10917 is a cytotoxic deoxycytidine analogue that causes DNA
fragmentation, G2/M-phase arrest, and apoptosis. This agent has been shown to
have antitumor activity against colorectal cancer (CRC) in preclinical studies
and to be tolerable in patients. The purpose of our phase II trial was to
evaluate the safety, efficacy and pharmacogenomics of DFP-10917 as well as DNA
damage studies in patients with advanced CRC refractory to cytotoxic
chemotherapy. Methods In this single-arm, Simon two-stage, phase II trial,
patients with chemotherapy-refractory advanced CRC received 2.0 mg/m2/day DFP
10917 via 14-day continuous infusion. Enrollment criteria included age >= 18
years, Eastern Cooperative Oncology Group status of 0 or 1, and adequate organ
function. The primary endpoint was 3-month progression-free survival, defined as
the proportion of patients who did not have progressive disease or death within 3
months of starting therapy. All patients who received any amount of DFP-10917
were included in the safety analysis. DNA damage study was assessed by comet
assay. Results Of 28 patients initially enrolled, 26 received DFP-10917. Three
patients (12%) were progression free at 3 months. The median progression-free
survival was 1.3 months (95% confidence interval, 1.3-1.6 months). There were no
complete or partial responses. Most patients (n = 20, 77%) had progressive
disease, and only six (23%) had stable disease at any time. The trial was
terminated according to the pre-planned stopping rule. The most frequent (>=5%)
medication-related grade 3 or higher adverse events were neutropenia (n = 10,
38%), fatigue (n = 4, 15%), anemia (n = 3, 12%), and leukopenia (n = 3, 12%). DNA
strand-breaks were detected after infusion (medians of % tail intensity were 2.89
and 12.64 on day 1 and day 15, respectively, p < 0.001, sign test). Conclusion
Overall, single-agent DFP-10917 did not show meaningful antitumor activity in
chemotherapy-refractory advanced CRC. The safety profile of DFP-10917 was
tolerable and similar to that observed in earlier clinical studies.
PMID- 29948358
TI - Survival and tolerance to sorafenib in Child-Pugh B patients with hepatocellular
carcinoma: a prospective study.
AB - Sorafenib has been widely used to treat unresectable hepatocellular carcinoma
(HCC) but most studies have been done in Child-Pugh A (CP-A) patients with well
preserved liver function. We evaluated the overall survival (OS) and tolerance to
sorafenib in a large cohort of Child-Pugh B (CP-B) HCC patients as compared to CP
A HCC patients. We prospectively studied 130 patients with advanced HCC who
started sorafenib between January 2011 and December 2015. Patients were
classified as CP-A (n = 65) or CP-B (n = 65). The average OS for all 130 patients
was 10 months. CP-A patients had a median survival rate significantly longer than
CP-B patients: 12 months vs. 6 months. The OS found in our group of CP-B patients
was 6.5 months, which is higher than that found in most studies done so far. When
stratified, our CP-B patients had better OS than ever reported. The dose of the
drug was interrupted due to adverse events (AEs) in 38 (29%) of the patients, of
whom 20 (30%) were CP-A patients and 18 (28%) were CP-B patients. This real-life
cohort of CP-B HCC patients treated with sorafenib had a higher survival than
that described in the literature, with a satisfactory safety profile. Despite the
high prevalence of severe AEs in CP-B patients, there were fewer treatment
interruptions in this group, indicating that Child-Pugh B patients can tolerate
treatment and may benefit from sorafenib.
PMID- 29948359
TI - Methionine gamma lyase from Clostridium sporogenes increases the anticancer
effect of doxorubicin in A549 cells and human cancer xenografts.
AB - The anti-cancer efficacy of methionine gamma-lyase (MGL) from Clostridium
sporogenes (C. sporogenes) is described. MGL was active against cancer models in
vitro and in vivo. The calculated EC50 values for MGL were 4.4 U/ml for A549, 7.5
U/ml for SK-BR3, 2.4 U/ml for SKOV3, and 0.4 U/ml for MCF7 cells. The combination
of doxorubicin (DOX) and MGL was more effective for A549 human lung cancer growth
inhibition than either agent alone in vitro and in vivo. MGL reduced the EC50 of
doxorubicin from 35.9 MUg/mL to 0.01-0.265 MUg/mL. The growth inhibitory effect
of DOX + MGL on A549 xenografts in vivo was reflective of the results obtained in
vitro. The inhibition rate of tumor growth in the combined arm was 57%,
significantly higher than that in the doxorubicin (p = 0.033)-alone arm.
PMID- 29948360
TI - Incidence and antimicrobial resistance trends in bloodstream infections caused by
ESKAPE and Escherichia coli at a large teaching hospital in Rome, a 9-year
analysis (2007-2015).
AB - The proportion of antimicrobial resistance (AMR) among the ESKAPE and Escherichia
coli (ESKAPEEc) pathogens causing bloodstream infection (BSI) increased
worldwide. We described longitudinal trends in ESKAPEEc BSI and AMR over 9 years
(2007-2015) at a large teaching hospital in Italy. Of 9720 unique BSI episodes,
6002 (61.7%) were caused by ESKAPEEc pathogens. The majority of these episodes
(4374; 72.9%) were hospital-onset infections. The most frequent pathogen was E.
coli (32.8%), followed by Staphylococcus aureus (20.6%), Klebsiella pneumoniae
(16.1%), and Pseudomonas aeruginosa (11.6%). There was a significant increase of
hospital-onset K. pneumoniae (from 2.3 to 5.0 per 10,000 patient-days; P = 0.001)
and community-onset E. coli (from 3.3 to 9. 1 per 10,000 emergency admissions; P
= 0.04) BSIs. Among hospital-onset BSIs, increases of extended-spectrum beta
lactamase (ESBL)-producing E. coli (from 25.4 to 35.2%, P = 0.006), carbapenemase
producing K. pneumoniae (from 4.2 to 51.6%, P < 0.001), and methicillin-resistant
S. aureus (from 33.9 to 44.4%, P < 0.001) BSIs were observed between the 2007
2009 and 2010-2012 study periods. In contrast, a decrease of BSIs caused by P.
aeruginosa resistant to ceftazidime (from 45.5 to 28.2%, P < 0.001),
ciprofloxacin (from 46 to 36.3%, P = 0.05), and meropenem (from 55 to 39.9%, P =
0.03) was observed through all 9 years of the study period. Among community-onset
BSIs, increases of BSIs caused by ESBL-producing E. coli (from 28.6 to 42.2%, P =
0.002) and carbapenemase-producing K. pneumoniae (from 0 to 17.6%) were observed
between the 2007-2009 and 2010-2012 study periods. Our findings show increased
rates of BSI and relative AMR for specific pathogen-health care setting
combinations, and call for continued active surveillance and infection control
policies.
PMID- 29948363
TI - Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients.
AB - The tick-borne bacterium Candidatus (Ca.) Neoehrlichia (N.) mikurensis is a cause
of "fever of unknown origin" because this strict intracellular pathogen escapes
detection by routine blood cultures. Case reports suggest that neoehrlichiosis
patients may display serological reactivity to Anaplasma (A.) phagocytophilum.
Since Anaplasma serology is part of the diagnostic work-up of undetermined fever
in European tick-exposed patients, we wanted to investigate (1) the prevalence of
A. phagocytophilum seropositivity among neoehrlichiosis patients, (2) the
frequency of misdiagnosed neoehrlichiosis patients among A. phagocytophilum
seropositive patients, and (3) the frequency of A. phagocytophilum and Ca. N.
mikurensis co-infections. Neoehrlichiosis patients (n = 18) were analyzed for A.
phagocytophilum IgM and IgG serum antibodies by indirect immunofluorescence
assay. Serum samples from suspected anaplasmosis patients (n = 101) were analyzed
for bacterial DNA contents by singleplex PCR specific for A. phagocytophilum and
Ca. N. mikurensis, respectively. One fifth of the neoehrlichiosis patients (4/18)
were seropositive for IgM and/or IgG to A. phagocytophilum at the time of
diagnosis. Among the patients with suspected anaplasmosis, 2% (2/101) were
positive for Ca. N. mikurensis by PCR whereas none (0/101) had detectable A.
phagocytophilum DNA in the serum. To conclude, patients with suspected
anaplasmosis may in fact have neoehrlichiosis. We found no evidence of A.
phagocytophilum and Ca. N. mikurensis co-infections in humans with suspected
anaplasmosis or confirmed neoehrlichiosis.
PMID- 29948361
TI - High levels of Staphylococcus aureus and MRSA carriage in healthy population of
Algiers revealed by additional enrichment and multisite screening.
AB - The purpose of the research is to characterize Staphylococcus aureus colonization
in healthy population of Algiers, to assess the impact on diagnostic performance
of systematic additional broth enrichment, and to ascertain the additional
benefits of multiple site screening. In order to more accurately determine the
prevalence of S. aureus colonization, the swab specimens from multiple screening
sites were incubated in brain-heart broth before agar plating. From 2009 to 2011,
1176 samples were collected from 459 participants (201 adults and 258 children).
The additional enrichment detection step significantly increased S. aureus
detection rates (p < 0.0001). S. aureus nasal detection was positive in 37.8% of
adults, and the addition of throat samplings significantly increased the S.
aureus detection rate up to 54.7% (p < 0.001). S. aureus nasal detection was
positive in 37.6% of children. The addition of throat samplings in children
significantly increased the S. aureus detection rate up to 53.1% (p < 0.001) and
that of anal samplings up to 59.7%. The overall prevalence of methicillin
resistant S. aureus was 5.2% (3% of adults and 7% of children). spa typing of all
isolates revealed a diverse but strongly clonal S. aureus population structure.
This approach involving multiple anatomical sampling sites and an additional
enrichment of the swabs before conventional culture significantly increases the
detection rate of S. aureus carriers and may prove valuable to improve global S.
aureus infection prevention.
PMID- 29948364
TI - Excretion in the mother's body: modifications of the larval excretory system in
the viviparous dermapteran, Arixenia esau.
AB - The vast majority of Dermaptera are free-living and oviparous, i.e., females lay
eggs within which embryonic development occurs until the larva hatches. In
contrast, in the epizoic dermapteran Arixenia esau, eggs are retained within
mother's body and the embryos and first instar larvae develop inside her
reproductive system. Such a reproductive strategy poses many physiological
challenges for a mother, one of which is the removal of metabolic waste generated
by the developing offspring. Here, we examine how the Arixenia females cope with
this challenge by analyzing features of the developing larval excretory system.
Our comparative analyses of the early and late first instar larvae revealed
characteristic modifications in the cellular architecture of the Malpighian
tubules, indicating that these organs are functional. The results of the electron
probe microanalyses suggest additionally that the larval Malpighian tubules are
mainly involved in maintaining ion homeostasis. We also found that the lumen of
the larval alimentary track is occluded by a cellular diaphragm at the midgut
hindgut junction and that cells of the diaphragm accumulate metabolic compounds.
Such an organization of the larval gut apparently prevents fouling of the
mother's organism with the offspring metabolic waste and therefore can be
regarded as an adaptation for viviparity.
PMID- 29948362
TI - Analyzing candidemia guideline adherence identifies opportunities for antifungal
stewardship.
AB - Candidemia epidemiology varies significantly by region; thus, local data are
essential for evidence-based decision-making in prophylaxis and treatment.
Current management strategies are derived from large randomized controlled trials
mostly executed in large high-volume tertiary care centers. Results may not be
entirely transferable to smaller hospitals. This study investigates epidemiology,
diagnosis, and treatment standards in six hospitals in the Cologne metropolitan
area (number of inhabitants approx. one million). We assessed adherence to the
current guideline of the European Society for Clinical Microbiology and
Infectious Diseases (ESCMID) and the Infectious Diseases Society of America
(IDSA) using the EQUAL Candida Score of the European Confederation of Medical
Mycology (ECMM). Data were documented by trained medical students as part of an
integrated research and teaching concept at the University of Cologne. Between
January 2014 and June 2017, 77 patients had candidemia, corresponding to an
incidence of 0.2 cases/1000 admissions. While 55 patients were enrolled, 22
patients were excluded due to incompletely retrievable health records.
Fluconazole monotherapy was the preferred first-line treatment in cases with
Candida albicans infection (21/29). A central vascular catheter was present in 40
patients and was removed in 17 (43%) during treatment. Overall mortality at 30
days was 44%. Patients reached a mean EQUAL Candida Score of 9.9 (range 8-14),
which was well below the maximum score of 22 for perfect guideline adherence. In
summary, management of candidemia differed from current European recommendations.
It remains unclear to what extent enhanced adherence would improve patient
outcome. Larger prospective studies need to answer that question.
PMID- 29948365
TI - Floral nectary and osmophore of Epipactis helleborine (L.) Crantz (Orchidaceae).
AB - The analysis of flowers collected at different stages of anthesis provides strong
evidence to conclude that the shell-shaped hypochile and the knobs of epichile
form a nectary. The scent comes from the aromatic constituents of nectar and the
epichile tissue and the apices of all tepals (osmophores). The comparison between
pollinated and unpollinated flowers revealed that the anthesis of unpollinated
flowers lasted up to the 16th day. The nectariferous secretory cells formed
single-layered epidermis and several layers of underlying parenchyma built by
small, isodiametric cells with thin walls and dense cytoplasm, relatively large
nuclei, supplied by collateral vascular bundles. During the floral lifespan, the
residues of secreted material were higher on the hypochile cells. The lipoid
carbohydrate material and lipid globules in the cell walls and in the cytoplasm
were localised. The abundance of starch grains was observed at the beginning of
anthesis and their gradual reduction during the flower lifespan. At the end of
anthesis in unpollinated flowers, the lipoid-carbohydrate-phenolic materials have
been demonstrated. The phenolic material was the same as in plastoglobuli. The
features such as irregular plasmalemma, the secretory vesicles that fuse with it,
fully developed dictyosomes, numerous profiles of ER indicate vesicle-mediated
process of secretion. The substances could be transported by vesicles to the
periplasmic space via granulocrine secretion and then to the external surface.
Both micro-channels and slightly developed periplasmic space were visible in the
hypochile epidermis. This is the first time for anatomical survey of secretory
tissue in pollinated and unpollinated flowers of E. helleborine.
PMID- 29948366
TI - Graviperception in maize plants: is amyloplast sedimentation a red herring?
AB - Land plants perceive gravity and respond to it in an organ-specific way; shoots
typically direct growth upwards, roots typically downwards. Historically, at
least with respect to maize plants, this phenomenon is attributed to three
sequential processes, namely graviperception, the transduction of the perceived
signal, and the graviresponse, resulting in a typical (re)positioning of the
organ or entire plant body relative to the gravivector. For decades,
sedimentation of starch-containing plastids within the cells of special tissues
has been regarded as the primary and initiating process fundamental for
gravitropic growth (starch-statolith hypothesis). Based on Popper's falsification
principle, uncompromising experiments were executed. The results indicate that
the model of graviperception based on amyloplast sedimentation does not apply to
maize seedlings.
PMID- 29948367
TI - Over-expression of a plasma membrane H+-ATPase SpAHA1 conferred salt tolerance to
transgenic Arabidopsis.
AB - The SpAHA1 gene, encoding a plasma membrane (PM) H+-ATPase (AHA) in Sesuvium
portulacastrum, was transformed into Arabidopsis plants, and its expression
increased salinity tolerance of transgenic Arabidopsis plants: seed germination
ratio, root growth, and biomass of transgenic plants were greater compared to
wild-type plants under NaCl treatment condition. Upon salinity stress, both Na+
and H+ effluxes in the roots of SpAHA1 expressing plants were faster than those
of untransformed plants. Transformed plants with SpAHA1 had lower Na+ and higher
K+ contents relative to wild-type plants when treated with NaCl, resulting in
greater K+/Na+ ratio in transgenic plants than in wild-type plants under salt
stress. Extent of oxidative stress increased in both transgenic and wild-type
plants exposed to salinity stress, but overexpression of SpAHA1 could alleviate
the accumulation of hydrogen peroxide (H2O2) induced by NaCl treatment in
transgenic plants relative to wild-type plants; the content of malondialdehyde
(MDA) was lower in transgenic plants than that in wild-type plants under salinity
stress. These results suggest that the higher H+-pumping activity generated by
SpAHA1 improved the growth of transgenic plants via regulating ion and reactive
oxygen species (ROS) homeostasis in plant cells under salinity stress.
PMID- 29948368
TI - Microstructural and histochemical characteristics of Lycium barbarum L. fruits
used in folk herbal medicine and as functional food.
AB - Lycium barbarum L. fruits, referred to as functional food, have long been used in
traditional and folk herbal medicine due to their therapeutic properties. The
fruit microstructure was analysed using light, scanning and transmission electron
microscopes. The distribution of bioactive compounds in drupe tissues was
assessed with histochemical and fluorescence assays. The analysis of the
microstructure has shown that the fruit is covered by a skin with an amorphous
cuticle and a layer of amorphous epicuticular waxes on the surface. The skin is
composed of a single-layered epidermis with thickened walls and one layer of
hypodermis with slightly thickened periclinal walls. The pericarp cells contain
different types of chromoplasts, which most often contained exhibited
reticulotubules/fibrils of carotenoid pigments and phytoferritine deposits. The
results of the histochemical assays demonstrated that the secondary metabolites
with high phytotherapeutic importance were located in all layers of the pericarp
and seeds and, specifically, in the drupe exocarp and endocarp. The
phytochemicals were represented by polysaccharides (LBP), lipid compounds
(carotenoids, essential oils, sesquiterpenes, steroids), polyphenols (tannins and
flavonoids), and alkaloids. This study, which is the first report of the
microstructure and localisation of bioactive compounds in wolfberries, is a
valuable complement of phytochemical analyses and can be helpful for enhancement
of the therapeutic effect of the fruit as well as preliminary assessment of the
medicinal potential in the search for new pharmaceuticals. Detailed anatomical
studies are crucial for exploration of determinants of fruit quality and useful
for identification of diagnostic taxonomic traits.
PMID- 29948369
TI - Plant versus animal based diets and insulin resistance, prediabetes and type 2
diabetes: the Rotterdam Study.
AB - Vegan or vegetarian diets have been suggested to reduce type 2 diabetes (T2D)
risk. However, not much is known on whether variation in the degree of having a
plant-based versus animal-based diet may be beneficial for prevention of T2D. We
aimed to investigate whether level of adherence to a diet high in plant-based
foods and low in animal-based foods is associated with insulin resistance,
prediabetes, and T2D. Our analysis included 6798 participants (62.7 +/- 7.8
years) from the Rotterdam Study (RS), a prospective population-based cohort in
the Netherlands. Dietary intake data were collected with food-frequency
questionnaires at baseline of three sub-cohorts of RS (RS-I-1: 1989-1993, RS-II
1: 2000-2001, RS-III-1: 2006-2008). We constructed a continuous plant-based
dietary index (range 0-92) assessing adherence to a plant-based versus animal
based diet. Insulin resistance at baseline and follow-up was assessed using
homeostasis model assessment of insulin resistance (HOMA-IR). Prediabetes and T2D
were collected from general practitioners' records, pharmacies' databases, and
follow-up examinations in our research center until 2012. We used multivariable
linear mixed models to examine association of the index with longitudinal HOMA
IR, and multivariable Cox proportional-hazards regression models to examine
associations of the index with risk of prediabetes and T2D. During median 5.7,
and 7.3 years of follow-up, we documented 928 prediabetes cases and 642 T2D
cases. After adjusting for sociodemographic and lifestyle factors, a higher score
on the plant-based dietary index was associated with lower insulin resistance
(per 10 units higher score: beta = -0.09; 95% CI: - 0.10; - 0.08), lower
prediabetes risk (HR = 0.89; 95% CI: 0.81; 0.98), and lower T2D risk [HR = 0.82
(0.73; 0.92)]. After additional adjustment for BMI, associations attenuated and
remained statistically significant for longitudinal insulin resistance [beta =
0.05 (- 0.06; - 0.04)] and T2D risk [HR = 0.87 (0.79; 0.99)], but no longer for
prediabetes risk [HR = 0.93 (0.85; 1.03)]. In conclusion, a more plant-based and
less animal-based diet may lower risk of insulin resistance, prediabetes and T2D.
These findings strengthen recent dietary recommendations to adopt a more plant
based diet.Clinical Trial Registry number and website NTR6831,
http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831 .
PMID- 29948370
TI - Direct comparative effectiveness and safety between non-vitamin K antagonist oral
anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a
systematic review and meta-analysis of observational studies.
AB - The non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly
prescribed in clinical practice for stroke prevention in patients with
nonvalvular atrial fibrillation (AF). Direct comparisons between NOACs in trials
are lacking, leaving an important clinical decision-making gap. We aimed to
perform a systematic review and meta-analysis to summarize the evidence of
observational studies for direct comparative effectiveness and safety amongst
NOACs in patients with AF. Conference proceedings and electronic databases
including MEDLINE, CINAHL, EMBASE and PUBMED were systematically searched. We
included observational studies directly comparing individual NOACs in patients
with nonvalvular AF who were aged >= 18 years for stroke prevention. Primary
outcome included effectiveness outcome (stroke or systemic embolism) and safety
outcome (major bleeding). Data were extracted in duplicated by two reviewers
independently. A random-effects meta-analysis was conducted to synthesize the
data from included observational studies. We used the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) to rate the overall quality of
evidence for each outcome. Fifteen studies were included for qualitative
synthesis, twelve studies for meta-analyses. It was found that rivaroxaban and
dabigatran were similar with regard to risk of stroke or systemic embolism
(Hazard ratio [HR] = 1.00, 95% CI 0.91-1.10; evidence quality: low), but
rivaroxaban was associated with higher risk of major bleeding (HR = 1.39, 95% CI
1.28-1.50; evidence quality: moderate). Compared with apixaban, a significantly
higher risk of major bleeding was observed with rivaroxaban (HR = 1.71, 95% CI
1.51-1.94; evidence quality: low). Apixaban was associated with lower risk of
major bleeding, in comparison with dabigatran (HR = 0.80, 95% CI 0.68-0.95;
evidence quality: low). No differences in risk of stroke or systemic embolism was
observed between rivaroxaban versus apixaban, and apixaban versus dabigatran. In
this study, apixaban was found to have the most favorable safety profile amongst
the three NOACs. No significant difference was observed in risk of stroke or
systemic embolism between the NOACs. Such findings may provide some decision
making support for physicians regarding their choices amongst NOACs in patients
with AF.Registration PROSPERO (identifier: CRD42016052908).
PMID- 29948371
TI - Will biomarker-based diagnosis of Alzheimer's disease maximize scientific
progress? Evaluating proposed diagnostic criteria.
AB - A recently published framework for the diagnosis of Alzheimer's disease (AD) in
research studies would allow diagnosis on the sole basis of two biomarkers (beta
amyloid and pathologic tau), even in people with no objective or subjective
memory or cognitive changes. This revision will have substantial implications for
future Alzheimer's research, and the changes should be rigorously evaluated
before widespread adoption. We propose three principles for evaluating any
revision to diagnostic frameworks for AD: (1) does the revision improve the
validity of the diagnosis; (2) does the revision improve the reliability or
reduce the expense of the diagnosis; and (3) will the revision foster innovative
and rigorous research across populations. The new diagnostic framework is
unlikely to achieve any of these goals. Instead, it has the potential to handicap
future researchers, and slow progress towards identifying effective strategies to
prevent or treat AD.
PMID- 29948372
TI - The i2Snake Robotic Platform for Endoscopic Surgery.
AB - Endoscopic procedures have transformed minimally invasive surgery as they allow
the examination and intervention on a patient's anatomy through natural orifices,
without the need for external incisions. However, the complexity of anatomical
pathways and the limited dexterity of existing instruments, limit such procedures
mainly to diagnosis and biopsies. This paper proposes a new robotic platform: the
Intuitive imaging sensing navigated and kinematically enhanced ([Formula: see
text]) robot that aims to improve the field of endoscopic surgery. The proposed
robotic platform includes a snake-like robotic endoscope equipped with a camera,
a light-source and two robotic instruments, supported with a robotic arm for
global positioning and for insertion of the [Formula: see text] and a master
interface for master-slave teleoperation. The proposed robotic platform design
focuses on ergonomics and intuitive control. The control workflow was first
validated in simulation and then implemented on the robotic platform. The results
are consistent with the simulation and show the clear clinical potential of the
system. Limitations such as tendon backlash and elongation over time will be
further investigated by means of combined hardware and software solutions. In
conclusion, the proposed system contributes to the field of endoscopic surgical
robots and could allow to perform more complex endoscopic surgical procedures
while reducing patient trauma and recovery time.
PMID- 29948373
TI - Comparison of Marker-Based and Stereo Radiography Knee Kinematics in Activities
of Daily Living.
AB - Movement of the marker positions relative to the body segments obscures in vivo
joint level motion. Alternatively, tracking bones from radiography images can
provide precise motion of the bones at the knee but is impracticable for
measurement of body segment motion. Consequently, researchers have combined
marker-based knee flexion with kinematic splines to approximate the translations
and rotations of the tibia relative to the femur. Yet, the accuracy of predicting
six degree-of-freedom joint kinematics using kinematic splines has not been
evaluated. The objectives of this study were to (1) compare knee kinematics
measured with a marker-based motion capture system to kinematics acquired with
high speed stereo radiography (HSSR) and describe the accuracy of marker-based
motion to improve interpretation of results from these methods, and (2) use HSSR
to define and evaluate a new set of knee joint kinematic splines based on the in
vivo kinematics of a knee extension activity. Simultaneous measurements were
recorded from eight healthy subjects using HSSR and marker-based motion capture.
The marker positions were applied to three models of the lower extremity to
calculate tibiofemoral kinematics and compared to kinematics acquired with HSSR.
As demonstrated by normalized RMSE above 1.0, varus-valgus rotation (1.26),
medial-lateral (1.26), anterior-posterior (2.03), and superior-inferior
translations (4.39) were not accurately measured. Using kinematic splines
improved predictions in varus-valgus (0.81) rotation, and medial-lateral (0.73),
anterior-posterior (0.69), and superior-inferior (0.49) translations. Using
splines to predict tibiofemoral kinematics as a function knee flexion can lead to
improved accuracy over marker-based motion capture alone, however this technique
was limited in reproducing subject-specific kinematics.
PMID- 29948374
TI - Dynamics of Intrinsic Glucose Uptake Kinetics in Human Mesenchymal Stem Cells
During Chondrogenesis.
AB - Chondrogenesis of human mesenchymal stem cells (hMSCs) is an important biological
process in many applications including cartilage tissue engineering. We
investigated the glucose uptake characteristics of aggregates of hMSCs undergoing
chondrogenesis over a 3-week period both experimentally and by using a
mathematical model. Initial concentrations of glucose in the medium were varied
from 1 to 4.5 g/L to mimic limiting conditions and glucose uptake profiles were
obtained. A reaction-diffusion mathematical model was implemented and solved to
estimate kinetic parameters. Experimental glucose uptake rates increased with
culture time for aggregates treated with higher initial glucose concentrations (3
and 4.5 g/L), whereas they decreased or remained constant for those treated with
lower initial glucose concentrations (1 and 2 g/L). Lactate production rate
increased by as much as 40% for aggregates treated with higher initial glucose
concentrations (2, 3 and 4.5 g/L), whereas it remained constant for those treated
with 1 g/L initial glucose concentration. The estimated DNA-normalized maximum
glucose uptake rate decreased by a factor of 9 from day 0-2 (12.5 mmol/s/g DNA)
to day 6-8 (1.5 mmol/s/g DNA), after which it started to increase. On day 18-20,
its value (17.5 mmol/s/g DNA) was about 11 times greater than its lowest value.
Further, the extracellular matrix levels of aggregates at day 14 and day 21
correlated with their overall glucose uptake and lactate production. The results
suggest that during chondrogenesis, for optimal results, cells require increasing
amounts of glucose. Our results also suggest that diffusion limitations play an
important role in glucose uptake even in the smaller size aggregate model of
chondrogenesis. Further, the results indicate that glucose uptake or lactate
production can be a tool for predicting the end quality of tissue during the
process of chondrogenesis. The estimated kinetic parameters can be used to model
glucose requirements in cartilage tissue engineering applications.
PMID- 29948375
TI - Dexmedetomidine facilitates extubation in children who require intubation and
respiratory support after airway foreign body retrieval: a case-cohort analysis
of 57 cases.
AB - PURPOSE: This study aimed to investigate whether dexmedetomidine had sedative
weaning advantage for extubation after airway foreign body (FB) removal in
children. METHODS: A retrospective case-cohort comparison study with total of 57
critical children who required mechanical ventilation after rigid bronchoscopy
was performed. After tracheal intubation, group D (received dexmedetomidine 1
ug/kg over 10 min, followed by an infusion of 0.8 ug/kg/h), and group RP
(received remifentanil-propofol 6-10 ug/kg/h and 1-3 mg/kg/h, respectively). The
primary outcome was successful extubation rate on first weaning trial. The minor
outcomes included weaning time, emergency agitation, coughing score and the
incidence of respiratory adverse complications on emergency. MAIN RESULTS: All 57
patients were included in the analysis, with 30 patients in group D and 27
controlled cases in group RP. The success rate of first weaning trial in the D
group was 96.7 vs 77.8% in the RP group, risk ratio (RR) 1.56, 95% CI [0.78
1.98]. Time for resuming spontaneous breathing after termination infusion was
shorter in the D group (median 8 min, IQR 15 min) vs RP group (median 12 min, IQR
19 min, P = 0.02, RR 0.56, 95% CI 0.14-6.57). CONCLUSIONS: In mechanical
ventilation of pediatric patients following rigid bronchoscopy, in comparison to
remifentanil-propofol, dexmedetomidine is proved to have high success rate for
weaning strategy. WHAT IS ALREADY KNOWN?: Remifentanil is proved to be effective
for weaning in ICU patients. Dexmedetomedine can provide similar rates of smooth
extubation for pediatric patients who underwent airway surgery. WHAT THIS ARTICLE
ADDS?: Invasive ventilation is used for patients with severe comorbidity after
airway surgery, but the correct strategy for pediatric extubation after removal
of airway foreign body remains unclear. For these patients with short-term
mechanical ventilation, dexmedetomedine may improve the extubation rate, when
compared with remifentanil-propofol.
PMID- 29948376
TI - Clinical and genetic study of Tunisian families with genetic generalized
epilepsy: contribution of CACNA1H and MAST4 genes.
AB - Genetic generalized epilepsies (GGE) (childhood absence epilepsy (CAE), juvenile
myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures
(GTCS)) are mainly determined by genetic factors. Since few mutations were
identified in rare families with autosomal dominant GGE, a polygenic inheritance
was suspected in most patients. Recent studies on large American or European
cohorts of sporadic cases showed that susceptibility genes were numerous although
their variants were rare, making their identification difficult. Here, we
reported clinical and genetic characteristics of 30 Tunisian GGE families,
including 71 GGE patients. The phenotype was close to that in sporadic cases.
Nineteen pedigrees had a homogeneous type of GGE (JME-CAE-CGTS), and 11 combined
these epileptic syndromes. Rare non-synonymous variants were selected in probands
using a targeted panel of 30 candidate genes and their segregation was determined
in families. Molecular studies incriminated different genes, mainly CACNA1H and
MAST4. The segregation of at least two variants in different genes in some
pedigrees was compatible with the hypothesis of an oligogenic inheritance, which
was in accordance with the relatively low frequency of consanguineous probands.
Since at least 2 susceptibility genes were likely shared by different
populations, genetic factors involved in the majority of Tunisian GGE families
remain to be discovered. Their identification should be easier in families with a
homogeneous type of GGE, in which an intra-familial genetic homogeneity could be
suspected.
PMID- 29948377
TI - Association of CXCR2 genotype variations with HCV clearance in a Chinese
population.
AB - Chemokines are known to play a vital role in guiding and regulating the immune
response to viral infections. The chemokine CXC subfamily is a major subfamily in
the chemokine family. Outcomes of hepatitis C virus (HCV) infection, as well as
the response to treatment, depend on virus and host factors. Here we recruited
chronic hepatitis C (CHC) patients to perform an association study between three
single nucleotide polymorphisms (SNPs) (CXCR2 rs1126579, CXCL10 rs8878 and CXCL10
rs3921) and HCV infection outcomes and treatment responses among a Chinese
population, using primarily a TaqMan assay. Multivariate logistic regression
analysis was performed to identify the influencing factors on HCV infection
outcome and treatment response. The results showed that subjects with the CXCR2
rs1126579 TT genotype had a significantly increased possibility of HCV
spontaneous clearance (Dominant model: adjusted OR = 1.32, 95% CI = 1.06-1.64; P
= 0.013). Additionally, CHC patients carrying the CXCR2 rs1126579 TT genotype
were also more likely to achieve a sustained virological response (SVR) (Dominant
model: adjusted OR = 0.49, 95% CI = 0.29-0.84; P = 0.010). We also established a
predictive model for HCV treatment response including the CXCR2 rs1126579 SNP
status, albumin (ALB) levels and baseline HCV RNA levels, which produced an area
under the curve (AUC) of about 0.660. These findings highlight that variant CXCR2
rs1126579 genotypes are associated with HCV clearance within the Chinese
population.
PMID- 29948378
TI - Inhibition of expression of BmNPV cg30 by bmo-miRNA-390 is a host response to
baculovirus invasion.
AB - Bombyx mori larvae exhibit in vivo defensive reactions immediately after invasion
by a virus. One of these defense systems is to express appropriate microRNAs
(miRNAs) to respond to the infection. A novel Bombyx mori-encoded miRNA, bmo-miR
390, was identified previously by high-throughput sequencing. Based on
bioinformatic predictions, the Bombyx mori nuclear polyhedrosis virus cg30 gene
(BmNPV-cg30) is one of the target genes of bmo-miR-390. In this study, expression
vectors with an enhanced green fluorescence protein (EGFP) or a luciferase (luc)
reporter gene together with bm-miR-390 or the cg30 3' UTR were constructed and
used to co-transfect BmN cells. Using a dual luciferase reporter (DLR) assay, we
found that bmo-miR-390 significantly downregulates the expression of BmNPV-cg30
(P < 0.05) in vitro. Moreover, artificially synthesized bmo-miR-390 mimics
enhanced the regulatory effect of bmo-miR-390, while an inhibitor eliminated the
inhibitory effect. These results show for the first time that bmo-miR-390 can
effectively downregulate the expression of BmNPV-cg30 in BmNPV-infected BmN
cells.
PMID- 29948379
TI - Cottontail rabbits shed clade 2.3.4.4 H5 highly pathogenic avian influenza A
viruses.
AB - : During 2014-2015, clade 2.3.4.4 H5Nx highly pathogenic (HP) avian influenza A
viruses (IAV) were first detected in North America and subsequently caused one of
the largest agricultural emergencies in U.S. HISTORY: Recent evidence has
suggested that cottontail rabbits can shed multiple IAV subtypes. We
experimentally infected cottontail rabbits with three HP H5Nx IAVs. All rabbits
tested shed virus on at least one day by at least one route. Cottontail rabbits
appear to be an exception to the limited capacity for replication that has been
previously reported for certain other mammalian species inoculated with clade
2.3.4.4 HP H5Nx avian influenza A viruses.
PMID- 29948380
TI - BCP/PC mutation prevalence and their association with HBV replication in HIV/HBV
co-infected patients.
AB - The high prevalence (14.3%) of HIV/HBV co-infections reported in west China makes
it necessary to screen concurrent HBV infection in HIV carriers. HBV B genotype
was shown to be dominant in 54 cases of HIV/HBV co-infection, accounting for
81.48% of the total. The total drug resistance rate observed was 3.70%. A1762T,
G1764A and G1896A mutations were common mutations identified in the BCP/PC
region. However, the prevalence of the G1896A mutation was significantly high
among the HBeAg negative HIV/HBV co-infected patients, and may be associated with
high HBV replication. Mutations in the PC region are related to the loss in
synthesis of HBeAg and may accelerate HBV replication in HIV positive patients.
PMID- 29948381
TI - Molecular characterization of an imported dengue virus serotype 4 isolate from
Thailand.
AB - The epidemic of dengue virus infections has spread markedly in Yunnan province of
China in recent years due to an increase in the number of imported dengue cases.
To the best of our knowledge, the present study is the first to report a whole
genome sequence and molecular characterization of an imported DENV-4 isolate from
Thailand. The current strain, 2013JH285, has an RNA genome of 10,772 nucleotides
that shares 99.0% nucleotide and 99.7% amino acid sequence identity with the 2013
Thailand strain CTI2-13. Phylogenetic analysis of the whole genome sequence
revealed that the 2013JH285 strain belongs to genotype I of DENV-4. Recombination
analysis suggested that the 2013JH285 strain originated from inter-genotypic
recombination of DENV-4 strains. The new complete DENV-4 genome sequence reported
here might contribute to further understanding of the molecular epidemiology and
disease surveillance of DENV-4 in China.
PMID- 29948382
TI - Atmospheric-pressure plasma irradiation can disrupt tobacco mosaic virus
particles and RNAs to inactivate their infectivity.
AB - Low-temperature atmospheric-pressure air plasma is a source of charged and
neutral gas species. In this study, N-carrying tobacco plants were inoculated
with plasma irradiated and non-irradiated tobacco mosaic virus (TMV) solution,
resulting in necrotic local lesions on non-irradiated, but not on irradiated, TMV
inoculated leaves. Virus particles were disrupted by plasma irradiation in an
exposure-dependent manner, but the viral coat protein subunit was not. TMV RNA
was also fragmented in a time-dependent manner. These results indicate that
plasma irradiation of TMV can collapse viral particles to the subunit level,
degrading TMV RNA and thereby leading to a loss of infectivity.
PMID- 29948383
TI - Genomic characterization of circoviruses associated with acute gastroenteritis in
minks in northeastern China.
AB - Mink circovirus (MiCV), a virus that was newly discovered in 2013, has been
associated with enteric disease. However, its etiological role in acute
gastroenteritis is unclear, and its genetic characteristics are poorly described.
In this study, the role of circoviruses (CVs) in mink acute gastroenteritis was
investigated, and the MiCV genome was molecularly characterized through sequence
analysis. Detection results demonstrated that MiCV was the only pathogen found in
this infection. MiCVs and previously characterized CVs shared genome
organizational features, including the presence of (i) a potential stem
loop/nonanucleotide motif that is considered to be the origin of virus DNA
replication; (ii) two major inversely arranged open reading frames encoding
putative replication-associated proteins (Rep) and a capsid protein; (iii) direct
and inverse repeated sequences within the putative 5' region; and (iv) motifs in
Rep. Pairwise comparisons showed that the capsid proteins of MiCV shared the
highest amino acid sequence identity with those of porcine CV (PCV) 2 (45.4%) and
bat CV (BatCV) 1 (45.4%). The amino acid sequence identity levels of Rep shared
by MiCV with BatCV 1 (79.7%) and dog CV (dogCV) (54.5%) were broadly similar to
those with starling CV (51.1%) and PCVs (46.5%). Phylogenetic analysis indicated
that MiCVs were more closely related to mammalian CVs, such as BatCV, PCV, and
dogCV, than to other animal CVs. Among mammalian CVs, MiCV and BatCV 1 were the
most closely related. This study could contribute to understanding the potential
pathogenicity of MiCV and the evolutionary and pathogenic characteristics of
mammalian CVs.
PMID- 29948384
TI - Molecular detection and sequence analysis of porcine circovirus type 3 in sow
sera from farms with prolonged histories of reproductive problems in Hunan,
China.
AB - A newly emerging porcine circovirus, designated PCV3, has been reported in
various countries (USA, Poland, South Korea and China) since 2017. Its presence
may be associated with porcine dermatitis and nephropathy syndrome (PDNS),
reproductive failure, and multisystem inflammation. In this study, we report
identification of PCV3 in cases of reproductive failure in various regions in
Hunan, China. From January 2015 to December 2016, sera were collected from 190
sows from seven farms with reproductive problems. Specifically, 85 samples were
from sows with a history of reproductive failure, whereas the remaining 105 were
from healthy sows. The PCV3-positive rate was significantly higher in sows with
reproductive failure (45.9%) than in healthy sows (21.9%), based on quantitative
PCR (qPCR) assays. Although phylogenetic analysis based on the cap gene suggested
that these PCV3 isolates belonged to the clade PCV3a, amino acid sequence
variations in the Cap protein still occurred among these isolates, and these
might have contributed to antigenic alterations of the Cap protein, based on the
Jameson-Wolf antigenic index. Finally, we concluded that PCV3 was circulating in
sows in Hunan province, China. However, the association of PCV3 with reproductive
failure in sows and its potential for vertical transmission need to be studied
further.
PMID- 29948385
TI - Genomic analysis of a novel isolate Heliothis virescens ascovirus 3i (HvAV-3i)
and identification of ascoviral repeat ORFs (aros).
AB - Ascoviruses are circular double-stranded DNA viruses that infect insects. Herein
we sequenced and analyzed the genome of the previously unrecorded ascovirus
isolate Heliothis virescens ascovirus 3i (HvAV-3i). The genome size is 185,650 bp
with 181 hypothetical open reading frames (ORFs). Additionally, definition based
on ascovirus repeated ORFs (aros) is proposed; whereby the 29 aros from all
sequenced Ascoviridae genomes are divided into six distinct groups. The
topological relationship among the isolates of Heliothis virescens ascovirus 3a
is (HvAV-3f, {HvAV-3h, [HvAV-3e, (HvAV-3g, HvAV-3i)]}) with every clade well
supported by a Bayesian posterior probability of 1.00 and a Bootstrap value of
100%.
PMID- 29948386
TI - Early tumor shrinkage and depth of response in patients with advanced gastric
cancer: a retrospective analysis of a randomized phase III study of first-line S
1 plus oxaliplatin vs. S-1 plus cisplatin.
AB - BACKGROUND: We investigated early tumor shrinkage (ETS) and depth of response
(DpR) using data from the G-SOX study comparing S-1 plus oxaliplatin with S-1
plus cisplatin as the first-line treatment for advanced gastric cancer (AGC).
METHODS: ETS was determined as % decrease in the sum of the longest diameters of
the target lesions at the first evaluation of week 6 compared to baseline. DpR
was the maximum % shrinkage during the study treatment. The impact of ETS (cutoff
value 20%) and DpR (continuous value) on progression-free survival (PFS) and
overall survival (OS) were assessed by the log-rank test and Cox regression
analysis including prognostic factors obtained in the G-SOX study; ECOG
performance status, baseline sum of tumor diameters, disease status
(recurrent/unresectable), and histology (diffuse/intestinal). RESULTS: Among 685
patients enrolled in the G-SOX study, 632 patients who had the first tumor
evaluation were analyzed. Patients with ETS >= 20% had longer PFS (median 4.5 vs.
2.8 months, p < 0.0001) and OS (median 14.8 vs. 10.5 months, p < 0.0001) than
those with ETS < 20%. Adjusted hazard ratios of ETS < 20 vs. >= 20% were 0.606
(95% confidence interval (CI) 0.506-0.725) for PFS and 0.589 (95% CI 0.492-0.704)
for OS. DpR was also significantly associated with PFS and OS (both p < 0.0001).
These results were similar between the SOX and CS groups. CONCLUSIONS: In AGC
patients receiving the first-line therapy, ETS and DpR might be predictors for
PFS and OS.
PMID- 29948387
TI - The clinical implications of FDG-PET/CT differ according to histology in advanced
gastric cancer.
AB - BACKGROUND: The prognostic impact of preoperative 18F-FDG PET/CT in advanced
gastric cancer (AGC) remains a matter of debate. This study aims to evaluate the
prognostic impact of SUVmax in preoperative 18F-FDG PET/CT of AGC according to
histologic subtype, with a focus on the differences between tubular
adenocarcinoma and signet ring cell (SRC) carcinoma. METHODS: As a discovery set,
a total of 727 AGC patients from prospective database were analyzed according to
histologic subtype with Cox proportional hazard model and p-spline curves. In
addition, another 173 patients from an independent institution was assessed as an
external validation set. RESULTS: In multivariate analysis, high SUVmax in
preoperative 18F-FDG PET/CT of AGC was negatively correlated with disease-free
survival (DFS) and overall survival (OS) in patients with diffuse type (DFS: HR
2.17, P < 0.001; OS: HR 2.47, P < 0.001) or SRC histology (DFS: HR 2.26, P =
0.005; OS: HR 2.61, P = 0.003). This negative prognostic impact was not observed
in patients with intestinal type or well or moderately differentiated histology.
These findings have been consistently confirmed in a validation set. The p-spline
curves also showed a gradual increase in log HR as SUVmax rises only for SRC
histology and for diffuse-type AGC. Finally, a novel predictive model for
recurrence of AGC with diffuse type or SRC histology was generated and validated
based on the preoperative SUVmax. CONCLUSIONS: Preoperative high SUVmax of AGC is
a poor prognostic factor in those with diffuse type or SRC histology. This study
is the first to demonstrate the differential prognostic impact of preoperative
PET/CT SUVmax in AGC according to histologic subtype and provide a clue to
explain previous discrepancies in the prognostic impact of preoperative PET/CT in
AGC. Prospective studies are required to validate the role of preoperative SUVmax
in AGC.
PMID- 29948388
TI - Outcomes of endoscopic submucosal dissection for gastric epithelial neoplasm in
chronic kidney disease patients: propensity score-matched case-control analysis.
AB - BACKGROUND: Little is known about the outcomes of gastric endoscopic submucosal
dissection (ESD) in patients with chronic kidney disease (CKD). We compared the
efficacy and safety of ESD between CKD and non-CKD patients. METHODS: From
January 2005 to December 2014, 102 CKD patients underwent ESD for gastric
neoplasms at a tertiary medical institution were reviewed retrospectively. A
propensity score-matched control group (102 patients) was selected from non-CKD
patients to compare clinical outcomes between CKD and non-CKD patients. RESULTS:
En bloc resection (96.1%) and curative resection (88.2%) rates in the CKD group
did not significantly differ from those in the non-CKD group. Median procedure
times (25.0 vs. 21.5 min, p = 0.734) and perforation risk (p = 0.480) were
similar between groups. The CKD group showed a tendency towards more bleeding
events (p = 0.052) and had a significantly longer hospital stay (p = 0.001). In a
subgroup analysis, stage 3 CKD patients exhibited a bleeding risk comparable to
that exhibited by non-CKD patients (HR 1.35; 95% CI 0.36-5.06; p = 0.654),
whereas stage 4 (HR 5.79; 95% CI 1.52-22.0; p = 0.010) and stage 5 (HR 4.80; 95%
CI 1.58-14.6; p = 0.006) patients showed higher bleeding risks than non-CKD
patients. In a multivariate analysis, stage 4/5 CKD was a significant predictor
for bleeding risk (HR 4.99; 95% CI 1.32-18.8; p = 0.018). CONCLUSIONS: ESD for
gastric epithelial neoplasms can be performed in stage 3 CKD patients with
comparable efficacy and safety to that performed in non-CKD patients. Stage 4 and
5 CKD patients should be closely monitored for bleeding events after ESD.
PMID- 29948390
TI - FoxM1 is regulated by both HIF-1alpha and HIF-2alpha and contributes to
gastrointestinal stromal tumor progression.
AB - BACKGROUND: FoxM1 plays important regulatory roles in a variety of diseases.
However, the functional role of FoxM1 and mechanisms responsible for its
expression in gastrointestinal stromal tumor (GIST) is not thoroughly understood.
METHODS: FoxM1 protein expression and biological function were examined in human
GIST tissues and cells using immunohistochemistry, quantitative real-time PCR,
western blot, CCK-8, wound-healing- and Matrigel invasion assays, respectively.
The role of hypoxia-inducible factor (HIF) signaling in FoxM1 expression was
investigated using chromatin immunoprecipitation and luciferase reporter and in
vivo tumor growth assays. RESULTS: FoxM1 was highly expressed in highly
proliferative and migratory/invasive GIST specimens. Upregulation of FoxM1 was
positively correlated with the expression of HIF-1alpha and HIF-2alpha in GIST
specimens, and hypoxia-induced FoxM1 expression in GIST cells. Functionally,
ectopic expression of FoxM1 significantly promoted GIST cell proliferation, cell
cycle progression, migration and invasion, whereas the knockdown of endogenous
FoxM1 of hypoxic GIST cells had the opposite effects. Molecularly, FoxM1 was
transcriptionally regulated by HIF-2alpha under normoxia, whereas it was
upregulated by both HIF-1alpha and HIF-2alpha under hypoxia. The xenograft tumor
data further confirmed the regulated effect of HIF-1alpha and HIF-2alpha on
FoxM1, and demonstrated that the simultaneous downregulation of both HIF-1alpha
and HIF-2alpha inhibited GIST tumor growth. CONCLUSIONS: Our data demonstrated
the critical role of FoxM1 in promoting GIST progression and uncovered a novel
HIF-1alpha/HIF-2alpha-FoxM1 axis. These findings identify FoxM1 as a possible new
molecular target for designing novel therapeutic treatments to control GIST
progression.
PMID- 29948389
TI - Correction to: Favorable long-term outcomes of one-year adjuvant S-1 monotherapy
for pathological stage II or III gastric cancer treated at a high-volume center.
AB - In the original publication of this article, the 5-year OS rates of the S-1 group
in the ACTS-GC according to TNM-6 were described incorrectly in Table 4. The
revised Table 4 is given in this correction.
PMID- 29948391
TI - Bloodstream infection caused by S. aureus in patients with cancer: a 10-year
longitudinal single-center study.
AB - BACKGROUND: Staphylococcus aureus bloodstream infections (SABIs) represent a
significant cause of morbidity and mortality in cancer patients. In this study,
we compared infection characteristics and evaluated epidemiology and risk factors
associated to SABIs and 30-day attributable mortality in cancer patients.
METHODS: Clinical and microbiological data from patients with cancer and positive
blood cultures for S. aureus were retrieved during a 10-year period at an
oncology reference center. Analyses were performed according to type of
malignancy and infection with methicillin-resistant S. aureus (MRSA). Data was
evaluated using competing risk analyses to identify risk factors associated to 30
day mortality and used to create a point system for mortality risk
stratification. RESULTS: We included 450 patients and MRSA was documented in
21.1%. Hospital-acquired infection, healthcare-associated pneumonia, and type-2
diabetes were associated to MRSA. In patients with hematologic malignancies, MRSA
was more frequent if hospital-acquired, but less likely in primary bacteremia.
Variables associated to mortality included abdominal source of infection,
hematologic malignancy, MRSA, glucose levels > 140 mg/dL, and infectious
endocarditis; catheter removal and initiation of adequate treatment within 48 h
of positive blood culture were protective factors. From our designed mortality
prediction scale, patients with a score > 3 had a 70.23% (95%CI 47.2-85.3%)
probability of infection-related death at 30 days. CONCLUSION: SABIs are a
significant health burden for cancer patients. Risk factors for SABI-related
mortality in this population are varied and impose a challenge for management to
improve patient's outcomes. Risk stratification might be useful to evaluate 30
day mortality risk.
PMID- 29948392
TI - Couples' symptom burden in oncology care: perception of self and the other.
AB - BACKGROUND: The literature suggests that psychological distress and quality of
life are interdependent in couples coping with cancer. The current study seeks to
extend these findings to physical symptom burden, examining differences in
symptom self-rating and perception of partner symptoms. METHODS: Couples were
approached while waiting for an integrative oncology service. Fifty patients and
their partners completed the Edmonton Symptom Assessment Scale (ESAS-FS; twelve
symptoms, scores 0-10, 10 worst possible) and a Global Health measure (PROMIS10).
Patient and partner each also completed the ESAS-FS as it related to their
perception of the other's symptoms. ESAS distress subscales analyzed included
Global (GDS), Psychosocial (PSS), and Physical (PHS). Analyses included paired t
tests to examine all measures. RESULTS: Fifty-eight percent of patients were
female with most common cancer diagnoses of breast (22%), gastrointestinal (16%),
and thoracic/H&N (16%). For ESAS-FS self-ratings, patients had significantly
higher physical distress than partners, with a no significant difference in
psychosocial distress. For PROMIS10 self-ratings, patients reported significantly
lower global health and physical health, (p's < 0.001); no differences were found
for mental health between patients and caregivers. Patient rating of partner
physical distress (PHS, p = 0.01) was significantly higher than partner self
rating, with no significant difference observed in ratings for psychosocial
distress. Partner rating of patient psychosocial distress (PSS, p < 0.001) and
physical distress (PHS, p = 0.001) was significantly higher than that of patient
self-rating. CONCLUSIONS: Our findings suggest that both patients and partners
perceive physical distress of the other higher than self; however, patients may
be more sensitive to psychosocial distress in their partners.
PMID- 29948393
TI - Psychosocial consequences of diagnosis and treatment of lung cancer and
evaluation of the need for a lung cancer specific instrument using focus group
methodology.
AB - OBJECTIVES: Patients with lung cancer (LC) have high rates of psychosocial
symptoms and international guidelines recommend regular psychosocial screening
during treatment. This study evaluates psychosocial consequences of diagnosis and
treatment of LC in a qualitative way and evaluates the need for a LC specific
screening instrument. METHODS: Focus group meetings with LC patients were divided
by treatment type. Patients discussed psychological and social consequences of
diagnosis and treatment. Major themes were identified using content analysis.
Themes were re-evaluated in a subsequent focus group, in accordance with the
European Organization for Research and Treatment of Cancer (EORTC) guidelines.
RESULTS: Patients reported a range of psychosocial consequences, such as
frustration due to physical limitations, fear of recurrence, sadness of leaving
behind partner and children, and disappointing social support. Patients treated
with palliative intent specifically indicated insecurities about the future.
Patients from all treatment modalities indicated a need for family support during
treatment. No themes specific to LC arose. CONCLUSIONS: Patients with LC are
coping with a range of psychosocial consequences, independent of the type of
treatment they receive. Fear of recurrence/metastasis and insecurity about the
future were more prominent in patients receiving palliative chemotherapy. Themes
were not specific to LC; therefore, a screening instrument specific for the LC
population does not seem required. However, the current standard for screening is
considered insufficiently sensitive and a stepped screening approach with
specific screening tools and a clinical interview is suggested as usual care.
PMID- 29948394
TI - Correction to: Can early palliative care with anticancer treatment improve
overall survival and patient-related outcomes in advanced lung cancer patients? A
review of the literature.
AB - The original version of this article unfortunately incorrectly captured the title
for Table 2.
PMID- 29948395
TI - Family interactions in childhood leukemia: an exploratory descriptive study.
AB - BACKGROUND: A child's cancer not only affects the child in question, but also
their family members and even closes relatives and friends. The nature of this
disease is such that, while imposing a high level of care workload on the family,
it also affects various family aspects including personal, familial, and social
interactions and relationships, as well as family functioning. This study aims to
describe family interactions in childhood leukemia. METHODS: This study was an
exploratory descriptive study, conducted on 58 participants (40 family members
and 18 members of the health team), with purposeful sampling and semi-structured
interviews-63 personal interviews and four group interviews-in the research
context of the Cancer Hospital in Isfahan, 2016-2017. Data analysis in this study
was carried out with qualitative content analysis using the Graneheim method.
RESULTS: In the data analysis, four main categories and 13 subcategories were
revealed. The first category, changes in roles, included the subcategories of
super caregiver mother, supportive super father, role shift, self and others'
forgetfulness, and confusion in roles and tasks; the second category, changes in
interpersonal relationships, included the subcategories of changes in spousal
relationships, changes in parent-child relationships, and changes in
relationships between children; the third category, changes in social
interactions, included the subcategories of changes in relationships with
relatives, changes in relationships with peers, changes in relationships with the
therapy team, and changes in interaction with supportive social networks; and the
fourth category, changes in relationship with God, included the subcategories of
spiritual bond and spiritual illness. CONCLUSION: Regarding the findings of this
study, it is expected that health system policymakers in the country, while
striving to strengthen the positive aspect of changes in family relationships and
interactions, will develop and execute operational, comprehensive, and society
based plans in order to eliminate the barriers and problems of relationships
within the family, as well as in relation to the larger community, taking into
consideration the family's cultural and social beliefs.
PMID- 29948396
TI - Health care improvement and survivorship priorities of colorectal cancer
survivors: findings from the PORTAL colorectal cancer cohort survey.
AB - PURPOSE: Few population-level surveys have explored patient-centered priorities
for improving colorectal cancer survivors' care. Working with patients, we
designed a survey to identify care improvement and survivorship priorities.
METHODS: We surveyed a random sample of 4000 patients from a retrospective,
population-based cohort of colorectal cancer survivors diagnosed during 2010
2014. The survey included two multiple response questions: "What would you have
changed about your cancer diagnosis and treatment experience?" and "What are your
biggest health or lifestyle concerns (other than having cancer) since being
diagnosed?" Multivariable regression identified characteristics associated with
endorsement of health care experience and survivorship concerns. RESULTS: Survey
response rate was 50.2% (2000/3986). Fifty-three percent reported at least one
unmet need, most commonly for more information about life after treatment
(26.7%). Survivors of rectal cancer reported more needs than respondents with
colon cancer; persons of color reported more needs than non-Hispanic whites;
individuals without high school diplomas reported more needs than individuals
with more education. Fear of recurrence was the most common health/lifestyle
concern (58.9%). Respondents under age 65 reported nearly all health/lifestyle
concerns more often than respondents over age 74. Rectal cancer survivors
reported more concerns about activity limitation, changes, and body function and
appearance than colon cancer survivors. Persons of color were more likely to
report financial concerns than non-Hispanic whites. CONCLUSIONS: The greatest
needs for intervention are among survivors of rectal cancer, survivors of
minority racial/ethnic background, and survivors of younger age. Survivors with
low educational attainment and those with higher stage disease could also
benefit.
PMID- 29948397
TI - Feasibility of implementing an electronic social support and resource
visualization tool for caregivers in a neuro-oncology clinic.
AB - PURPOSE: The goals of this study were to assess the feasibility of a web-based
application-electronic Social Network Assessment Program (eSNAP)-to automate the
capture and visualization of family caregiver social network data of neuro
oncology patients. METHODS: Caregivers were recruited from a neuro-oncology
clinic at an NCI-designated comprehensive cancer center. Participants completed
baseline questionnaires on a laptop in clinic assessing demographic
characteristics. After baseline, participants were randomly assigned to either
create a social network visualization using eSNAP (intervention) or to usual care
(control) condition. Those who used eSNAP provided likeability/usability data.
All participants were asked to complete follow-up questionnaires at 3 and 6 weeks
after baseline to determine feasibility of longitudinal study. RESULTS: We
recruited 40 caregivers of patients with primary malignant brain tumor to
participate in this study. Participants rated eSNAP usability and likeability
highly, indicating that eSNAP would help them consider their available social
support. At 3 weeks, 90% of participants completed questionnaires and 82.5%
completed questionnaires at 6 weeks. CONCLUSIONS: There is a need to encourage
family caregivers of patients with primary malignant brain tumor to engage their
existing social network resources to help alleviate caregiver burden. Our
findings suggest that our web-based application to address this issue is feasible
to implement with high usability and likeability. This pilot study identified
minor changes to the intervention to improve effectiveness and has implications
for future research in this understudied population. TRIAL REGISTRATION:
clinicaltrials.gov, protocol number NCT03026699.
PMID- 29948398
TI - Coping strategies, trajectories, and their associations with patient-reported
outcomes among women with ovarian cancer.
AB - OBJECTIVE: Most women with ovarian cancer present with advanced stage disease and
face aggressive treatments, recurrence, and possible death, yet little is known
about how they cope. Our objective was to identify coping strategies used by
women with ovarian cancer and their trajectories of use after diagnosis and to
assess if coping trajectories are associated with subsequent anxiety, depression,
or quality of life. METHODS: Women with ovarian cancer completed questionnaires
including the Brief-COPE, HADS, and FACT at 3, 6, and 9 months after diagnosis
and the HADS and FACT at 12 months. Using data from 634 women who completed the 3
month questionnaire, factor analysis was conducted to identify coping strategy
clusters. Trajectory modeling was used to assess patterns of coping over time.
Associations between coping trajectory from 3 to 9 months and patient-reported
outcomes at 12 months were investigated using general linear models. RESULTS:
Three coping strategy clusters were identified. Use of "taking action/positive
framing" followed four distinct trajectories over time: low-stable (44%), medium
stable (32%), medium-decreasing (11%), high-stable (12%). Use of
"social/emotional support" had four trajectories: low-increasing (7%), low
decreasing (44%), medium-decreasing (40%), and high-stable (8%). Women either
"accepted their reality" (26%) or "used some denial" (74%). Women who accepted
reality reported significantly less anxiety and depression and better quality of
life at 12 months. Women with high-stable use of taking action/positive framing
reported less depression. Women with high-stable use of social/emotional support
reported better quality of life. CONCLUSIONS: Strategies to assist women with
acceptance, action-planning, positive-framing, and maintaining psychosocial
support should be considered.
PMID- 29948399
TI - Intramedullary nails in the treatment of the distal radius fractures.
AB - The distal radius fracture is a common injury in old persons. Its treatment
remains a critical challenge because of number of cases, the final cost of the
procedure, the level of X-ray irradiation, and the demand of technique of
fixation in osteoporotic bone. The entire closed procedure requires a strict
percutaneous nailing. This offers advantages in terms of postoperative pain, per
operative irradiation, and cost. The main problem was so far the ability to
insure a stable reduction in time. This point is discussed with the introduction
of the "Nail-o-Flex(r)" nail. A continuous series of 83 patients is introduced.
PMID- 29948400
TI - Diagnostic parameters in periprosthetic infections: the current state of the
literature.
AB - Despite progress in recent years, a definitive diagnosis of PPI is not yet
possible. Due to new diagnostic possibilities and the further development of
already existing diagnostic tools, a more accurate diagnostic clarification of
uncertain cases should be possible. The following article includes an overview of
common existing diagnostic tools and instruments, which will likely gain
importance in the future.
PMID- 29948401
TI - Real-time, intraoperative detection of residual breast cancer in lumpectomy
cavity walls using a novel cathepsin-activated fluorescent imaging system.
AB - PURPOSE: Obtaining tumor-free surgical margins is critical to prevent recurrence
in breast-conserving surgery but it remains challenging. We assessed the LUM
Imaging System for real-time, intraoperative detection of residual tumor.
METHODS: Lumpectomy cavity walls and excised specimens of breast cancer
lumpectomy patients were assessed with the LUM Imaging System (Lumicell, Inc.,
Wellesley MA) with and without intravenous LUM015, a cathepsin-activatable
fluorescent agent. Fluorescence at potential sites of residual tumor was
evaluated with a sterile hand-held probe, displayed on a monitor and correlated
with histopathology. RESULTS: Background autofluorescence was assessed in excised
specimens from 9 patients who did not receive LUM015. In vivo lumpectomy cavities
and excised specimens were then imaged in 15 women undergoing breast cancer
surgery who received no LUM015, 0.5, or 1 mg/kg LUM015 (5 women per dose). Among
these, 11 patients had invasive carcinoma with ductal carcinoma in situ (DCIS)
and 4 had only DCIS. Image acquisition took 1 s for each 2.6-cm-diameter surface.
No significant background normal breast fluorescence was identified. Elevated
fluorescent signal was seen from invasive cancers and DCIS. Mean tumor-to-normal
signal ratios were 4.70 +/- 1.23 at 0.5 mg/kg and 4.22 +/- 0.9 at 1.0 mg/kg (p =
0.54). Tumor was distinguished from normal tissue in pre-and postmenopausal women
and readings were not affected by breast density. Some benign tissues produced
fluorescent signal with LUM015. CONCLUSION: The LUM Imaging System allows rapid
identification of residual tumor in the lumpectomy cavity of breast cancer
patients and may reduce rates of positive margins.
PMID- 29948402
TI - New emerging roles of microRNAs in breast cancer.
AB - BACKGROUND: MicroRNAs constitute a large family of non-coding RNAs, which
actively participate in tumorigenesis by regulating a set of mRNAs of distinct
signaling pathways. An altered expression of these molecules has been found in
different tumorigenic processes of breast cancer, the most common type of cancer
in the female population worldwide. PURPOSE: The objective of this review is to
discuss how miRNAs become master regulators in breast tumorigenesis. METHODS: An
integrative review of miRNAs and breast cancer literature from the last 5 years
was done on PubMed. We summarize recent works showing that the defects on the
biogenesis of miRNAs are associated with different breast cancer characteristics.
Then, we show several examples that demonstrate the link between cellular
processes regulated by miRNAs and the hallmarks of breast cancer. Finally, we
examine the complexity in the regulation of these molecules as they are modulated
by other non-coding RNAs and the clinical applications of miRNAs as they could
serve as good diagnostic and classification tools. CONCLUSION: The information
presented in this review is important to encourage new directed studies that
consider microRNAs as a good tool to improve the diagnostic and treatment
alternatives in breast cancer.
PMID- 29948403
TI - Mortality after contralateral breast cancer in Denmark.
AB - PURPOSE: How a second breast cancer diagnosis affects survival in comparison with
unilateral breast cancer (UBC) is unclear. Prognostic factors for contralateral
breast cancer (CBC) are also not well established. We aimed to investigate the
survival pattern after CBC with particular focus on time between first and second
breast cancer diagnosis and age at CBC diagnosis. METHODS: Within the nationwide
Danish Breast Cancer Cooperative Group database, we identified 68,466 breast
cancer patients diagnosed during 1978-2012. Patients who subsequently developed
CBC were identified in a previously established database (N = 3004). Patients
were followed for breast cancer-specific death in the Danish Register of Causes
of Death until 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were
calculated using Cox proportional hazard regression models. Cumulative breast
cancer mortality from date of CBC was estimated using the Aalen-Johansen method.
RESULTS: Compared with UBC patients, the rate of dying from breast cancer was
more than twofold higher following a CBC diagnosis, after adjustment for age,
period, tumor characteristics, and treatment of the first breast cancer (HR 2.48;
95% CI 2.31-2.66). Short time interval (< 5 years) was associated with higher
breast cancer-specific mortality after CBC among patients < 70 years at CBC
diagnosis compared with longer time intervals, but not among patients >= 70 years
at CBC diagnosis. CONCLUSION: Breast cancer-specific mortality rates were
markedly higher after compared with before a CBC diagnosis. We found higher
breast cancer-specific mortality after CBC associated with a short interval
between diagnoses among patients diagnosed with CBC before age 70 years.
PMID- 29948404
TI - The relationship between tumour size and nodal status is more incompatible in
triple-negative tumours.
PMID- 29948405
TI - Validation of the newly proposed American Joint Committee on Cancer (AJCC) breast
cancer prognostic staging group and proposing a new staging system using the
National Cancer Database.
AB - BACKGROUND: The eighth edition of AJCC cancer staging manual incorporated
biomarker status into the prognostic staging group (PSG). We used data from
National Cancer Database (NCDB) to validate and improve the PSG. METHODS: All
patients had surgery and at least some systemic treatment (endocrine therapy,
chemotherapy or HER2 targeted therapy). Information from 420,520 patients was
assessed for potential predictors of overall survival (OS), including age at
diagnosis (age), tumor grade (G), hormonal receptor and HER2 status, and presence
of lymph vascular invasion (LVI), stratified by stage or sub-stages. Based on the
multivariate Cox analyses, we built different point systems to predict OS and
evaluated the different point systems by Akaike's information criterion (AIC),
Harrell's concordance index (C-index), and Uno's concordance index. RESULTS: Age,
G, hormonal receptor and HER2 status, LVI and being TNBC were significantly
associated with OS (all P < 0.0001). Three staging systems were correlated with
OS: system 1 was the conventional anatomic TNM staging; system 2 included TNM,
age, G, hormonal receptor, HER2, and LVI; system 3 included TNM, age, G, TNBC
versus non-TNBC, and LVI. System 3 (C-index; 0.7316; AIC: 488138.91) achieved the
best balance between predictive performance and goodness-of-fit to the NCDB data
as compared to system 2 (C-index: 0.7325; AIC: 498087.73) and system 1 (C-index:
0.716; AIC: 688536.49). CONCLUSIONS: The new PSG is a better staging system than
the conventional anatomic TNM system. Grouping breast cancer into TNBC versus non
TNBC may be simpler while retaining similar accuracy as using ER/PR/HER2 status
to predict OS.
PMID- 29948406
TI - Can HbA1c combined with fasting plasma glucose help to assess priority for GCK
MODY vs HNF1A-MODY genetic testing?
PMID- 29948407
TI - The response of serum Glypican-4 levels and its potential regulatory mechanism to
endurance training and chamomile flowers' hydroethanolic extract in
streptozotocin-nicotinamide-induced diabetic rats.
AB - AIMS: Glypican-4 (GPC-4) is a novel adipomyokine that enhances insulin signaling.
Glycosylphosphatidylinositol-specific phospholipase D (GPLD1) is thought to
release GPC-4 and is itself an insulin-regulated enzyme. Beneficial effects of
exercise training and chamomile flowers extract (CFE) are shown through
activation of PPARgamma, which is a promising drug target in diabetes and
associated with GPC-4 synthesis. This study investigated the effects of 14-week
treadmill running and CFE on serum GPC-4, GPLD1, and insulin levels in
streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. METHODS: Thirty-two
STZ-NA-induced diabetic male Wistar rats were randomly assigned to four groups:
control (C), training (T), CFE treatment (CFE), and training plus CFE treatment
(TCFE) groups. The training groups were exercised on treadmill 5 days/week and
the treating groups were fed with 200 mg/kg/day CFE in drinking water for 14
weeks. Finally, serum GPC-4, GPLD1, and insulin levels were analyzed via sandwich
ELISA. RESULTS: Compared to the control group, serum insulin levels were
significantly higher in the T, CFE, and TCFE groups (p < 0.05, p < 0.05, p <
0.01, respectively), while OGTT and serum GPLD1 levels were significantly lower
in the T, CFE, and TCFE groups (all p < 0.001). Changes in serum GPC-4 levels
were not significant. Serum GPLD1 levels were negatively correlated with insulin
levels and HOMA-IS (both p < 0.001). CONCLUSIONS: This study suggests that
endurance training and CFE may downregulate serum GPLD1 levels in STZ-NA-induced
diabetic rats, which associate with the serum insulin profile. However, the
results show that endurance training and CFE may not cause serum GPC-4 adaptation
in STZ-NA-induced diabetic rats.
PMID- 29948408
TI - Prevalence and predictors of depression and anxiety in adult patients with type 1
diabetes in tertiary care setting.
AB - AIMS: To determine gender and age differences in the prevalence of depression and
anxiety and their predictive factors in adult patients with type 1 diabetes
(DM1). METHODS: Random sample of DM1 adult patients from a tertiary care hospital
cohort. To evaluate the presence of depression and anxiety, psychological
evaluation was performed using structured clinical interview (MINI). For the
specific evaluation of fear of hypoglycemia (FH), FH-15 questionnaire was used.
RESULTS: 339 patients [51.6% male; 38.5 +/- 12.9 years; HbA1c 7.5 +/- 1.1% (58.5
+/- 14.2 mmol/mol); 20.1 +/- 12.0 years of DM1] met the inclusion criteria.
Prevalence of depression, anxiety, and FH in men vs. women was as follows (%):
depression: 15.4 vs. 33.5 (p < 0.05); anxiety: 13.7 vs. 26.2 (p < 0.05); and FH:
42.8 vs. 46.0 (p = NS). Among midlife female patients, prevalence of depression
and anxiety was higher compared to male. Moreover, comorbid depressive and
anxious symptoms were also higher in midlife female patients compared to age
matched male patients (3.5 vs. 14%, p < 0.05). Apart from age-related
vulnerability, female gender, poor glycemic control, and microvascular and
macrovascular complications were predictive factors for depressive and anxious
symptomatology. Unawareness hypoglycemia and anxiety-prone personality were
predictor factors for FH. CONCLUSIONS: In adults with DM1, prevalence of
depression and anxiety is higher in women. Midlife patients, in particular women,
show a significantly higher prevalence of anxiety symptoms and comorbid
depression and anxiety. The presence of secondary complications and sustained
poor glycemic control should alert to the possibility of these mental disorders,
especially in the most vulnerable age population; clinical, gender and age
related patterns could help to design more effective psychological assessment and
support in adult patients with DM1.
PMID- 29948409
TI - Physical activity during pregnancy is associated with a lower prevalence of
gestational diabetes mellitus in Vietnam.
AB - AIMS: To assess the association between physical activity (PA) during pregnancy
and the prevalence of gestational diabetes mellitus (GDM) accounting for sitting
time. METHODS: The study used data from a cohort study of 2030 pregnant women in
Vietnam. Women were recruited from six hospitals in Ha Noi, Hai Phong, and Ho Chi
Minh City. Baseline measurements including PA and GDM were taken at 24-28 weeks
of gestation. PA was assessed during the past 3 months before the interview using
the interviewer-administered Pregnancy Physical Activity Questionnaire. GDM was
diagnosed at 24-28 weeks of gestation using the 2013 World Health Organization
criteria. RESULTS: 1987 out of 2030 pregnant women were included in the final
analysis, of which 432 had GDM (21.7%). Women undertaking the highest level
(upper tertile) of PA during pregnancy appeared to have a lower risk of GDM [odds
ratio (OR) 0.70, 95% confidence interval (CI) 0.53-0.94, Ptrend 0.017] when
compared to those at the lowest tertile of PA. Similarly, women with increased
levels of moderate-intensive activity and household/caregiving activity during
pregnancy were associated with reduced risks of GDM (OR 0.66, 95% CI 0.50-0.86,
Ptrend 0.002 and OR 0.72, 95% CI 0.55-0.95, Ptrend 0.020, respectively). These
apparent inverse associations were not attenuated by their sitting time. There
were no significant associations between sitting time, light-intensity activity,
vigorous-intensity activity, occupation, sports/exercise, commuting, or meeting
exercise guidelines and GDM risk. CONCLUSIONS: High levels of PA, particularly
moderate-intensity and household/caregiving activities during pregnancy were
associated with a lower prevalence of GDM independent of sitting time.
PMID- 29948410
TI - Tomato CYCLOPS/IPD3 is required for mycorrhizal symbiosis but not tolerance to
Fusarium wilt in mycorrhiza-deficient tomato mutant rmc.
AB - Mycorrhizal symbiosis requires several common symbiosis genes including
CYCLOPS/IPD3. The reduced mycorrhizal colonisation (rmc) tomato mutant has a
deletion of five genes including CYCLOPS/IPD3, and rmc is more susceptible to
Fusarium wilt than its wild-type parental line. This study investigated the
genetic defects leading to both fungal interaction phenotypes and whether these
were separable. Complementation was performed in rmc to test the requirement for
CYCLOPS/IPD3 in mycorrhiza formation and Fusarium wilt tolerance. Promoter
analysis via GFP expression in roots was conducted to determine the role of
native regulatory elements in the proper functioning of CYCLOPS/IPD3.
CYCLOPS/IPD3 regulated by its native promoter, but not a 2*35S promoter, restores
mycorrhizal association in rmc. GFP regulated by the 2*35S promoter is not
expressed in epidermal cells of roots, indicating that expression of CYCLOPS/IPD3
in these cells is required for colonisation by the fungi utilised in this
research. CYCLOPS/IPD3 did not restore Fusarium wilt tolerance, however, showing
that the genetic requirements for mycorrhizal association and Fusarium wilt
tolerance are different. Our results confirm the expected role of CYCLOPS/IPD3 in
mycorrhizal symbiosis and suggest that Fusarium tolerance is conferred by one of
the other four genes affected by the deletion.
PMID- 29948411
TI - Ectomycorrhizal fungal communities in high mountain conifer forests in central
Mexico and their potential use in the assisted migration of Abies religiosa.
AB - Abies religiosa forests in central Mexico are the only overwinter refuge of the
monarch butterfly and provide important ecosystem services. These forests have
lost 55% of their original area and as a consequence, diversity and biotic
interactions in these ecosystems are in risk. The aim of this study was to
compare the soil fungal diversity and community structure in the Abies religiosa
forests and surrounding Pinus montezumae, Pinus hartwegii, and coniferous mixed
forest plant communities to provide data on ecology of mycorrhizal interactions
for the assisted migration of A. religiosa. We sampled soil from five coniferous
forests, extracted total soil DNA, and sequenced the ITS2 region by Illumina
MiSeq. The soil fungi community was integrated by 1746 taxa with a species
turnover ranging from 0.280 to 0.461 between sampling sites. In the whole
community, the more abundant and frequent species were Russula sp. (aff.
olivobrunnea), Mortierella sp.1, and Piloderma sp. (aff. olivacearum). The
ectomycorrhizal fungi were the more frequent and abundant functional group. A
total of 298 species (84 ectomycorrhizal) was shared in the five conifer forests;
these widely distributed species were dominated by Russulaceae and Clavulinaceae.
The fungal community composition was significantly influenced by altitude and the
lowest species turnover happened between the two A. religiosa forests even though
they have different soil types. As Pinus montezumae forests have a higher
altitudinal distribution adjacent to A. religiosa and share the largest number of
ectomycorrhizal fungi with it, we suggest these forests as a potential habitat
for new A. religiosa populations.
PMID- 29948412
TI - Behaviour of Quercus pollen in the air, determination of its sources and
transport through the atmosphere of Mexico City and conurbated areas.
AB - Pollen allergies have a remarkable clinical impact all over world. Quercus pollen
is the main allergen in many parts of world. Due to the health impacts caused by
exposure to oak pollen, the objectives of this study are to characterise the
aerobiological behaviour of Quercus pollen and to determine its potential sources
as well as their transport through the atmosphere of Mexico City and surrounding
areas between January 2012 and June 2015. Airborne Quercus pollen monitoring was
carried out simultaneously in five zones of Mexico City. The percentage of
Quercus pollen of the total pollen collected from the air showed that the highest
concentration was recorded in 2014, followed by 2012. The annual seasonal
variation indicated that flowering and pollen emission into the atmosphere began
between February and March. The maximum concentration of Quercus pollen was
reached at Cuajimalpa. In 2012, the amount of pollen grains was distributed in
March and April uniformly, whilst in 2014, the largest amount of pollen was
concentrated in March. In 2012 and 2014 (years with the highest pollen
concentrations), corresponding intraday variations were quite similar, with a low
relative maximum in the morning and the highest concentrations in the evening.
The largest values were recorded in 2014, and two processes can explain these. In
the afternoon, pollen from secondary forest is carried by southwesterly
converging winds, increasing the pollen concentration in Cuajimalpa. In the
evening, there is an additional pollen contribution from primary forest via
transport by NW winds.
PMID- 29948413
TI - Study of the Population Dynamics of Busseola fusca, Maize Pest.
AB - Busseola fusca is a maize and sorghum pest that can cause significant damage to
both crops. Given that maize is one of the main cereals grown in the worldwide,
this pest is a major challenge for maize production and therefore for the
economies of several countries . In this paper , based on the life cycle of B.
fusca, we propose a mathematical model to study the population dynamics of this
insect pest . A sensitivity analysis using the eFast method was performed to show
the most important parameters of the model. We present the theoretical analysis
of the model. More precisely, we derive a threshold parameter [Formula: see
text], called basic offspring number and show that the trivial equilibrium is
globally asymptotically stable whenever [Formula: see text], while if [Formula:
see text], the non trivial equilibrium is globally asymptotically stable. The
theoretical results are supported by numerical simulations.
PMID- 29948414
TI - Optimizing self-regulation of performance: is mental effort a cue?
AB - Accurate self-regulation of performance is important for trainees. Trainees rely
on cues to make monitoring judgments to self-regulate their performance. Ideally,
cues and monitoring judgements accurately reflect performance, as measured by cue
diagnosticity (the ability of a cue to predict performance) and monitoring
accuracy (the ability of a monitoring judgement to predict performance). However,
this process is far from perfect, emphasizing the need for more accurate cues and
monitoring judgements. Perhaps the mental effort of a task could be a cue used to
inform certainty judgements. The purpose of this study is to measure cue
utilization and cue diagnosticity of mental effort and monitoring accuracy of
certainty for self-regulation of performance. Focused on the task of ECG
interpretation, 22 PGY 1-3 Internal Medicine residents at McMaster University
provided a diagnosis for 10 ECGs, rating their level of certainty (0-100%) and
mental effort (Paas scale, 1-9). 220 ECGs completed by 22 participants were
analyzed using path analysis. There was a negative moderate path coefficient
between certainty and mental effort (beta = - 0.370, p < 0.001), reflecting cue
utilization. Regarding cue diagnosticity of mental effort, this was reflected in
a small negative path coefficient between mental effort and diagnostic accuracy
(beta = - 0.170, p = 0.013). Regarding monitoring accuracy, a moderate path
coefficient was observed between certainty and diagnostic accuracy (beta = 0.343,
p < 0.001). Our results support mental effort as a cue and certainty as a
monitoring judgement for self-regulated performance. Yet, reported correlations
are not very high. Future research is needed to identify additional cues.
PMID- 29948415
TI - Patterns of Bird-Bacteria Associations.
AB - Birds, with their broad geographic ranges and close association with humans, have
historically played an important role as carriers of human disease and as
reservoirs for drug-resistant bacteria. Here, we examine scientific literature
over a 15-year timespan to identify reported avian-bacterial associations and
factors that may impact zoonotic disease emergence by classifying traits of bird
species and their bacteria. We find that the majority of wild birds studied were
migratory, in temperate habitats, and in the order Passeriformes. The highest
diversity of bacteria was found on birds in natural habitats. The most frequently
reported bacteria were Escherichia coli, Salmonella enterica, and Campylobacter
jejuni. Of the bacteria species reported, 54% have shown pathogenicity toward
humans. Percentage-wise, more pathogens were found in tropical (vs. temperate)
habitats and natural (vs. suburban, urban, or agricultural) habitats. Yet, only
22% were tested for antibiotic resistance, and of those tested, 75% of bacteria
species were resistant to at least one antibiotic. There were no significant
patterns of antibiotic resistance in migratory versus non-migratory birds,
temperate versus tropical areas, or different habitats. We discuss biases in
detection and representation, and suggest a need for increased sampling in non
temperate zones and in a wider range of avian species.
PMID- 29948416
TI - Hierarchical structure and the influence of individual attributes in the captive
squirrel monkey (Saimiri collinsi).
AB - The dominance structure of primate social groups varies widely. In addition to
the groups' composition, intrinsic attributes such as sex, body size and life
experience are important factors that can affect hierarchical dominance
relations. All primates are social animals, and the social environment has a
direct influence on the physiological conditions of vital systems such as
immunological, reproductive and cardiovascular systems. In this study, we analyze
the hierarchical structure of Saimiri collinsi in captivity, including the
hierarchical structure type, the influence of individual intrinsic
characteristics (sex, age, weight and origin-born in captivity or in the wild)
based on the prior-attributes model, the relation between agonistic behavior
frequency and hierarchical position, and hierarchy steepness, which represents
the dominance gradient. We found that the group order was characterized by a
partial hierarchy: a dominance position could be occupied by more than one
individual simultaneously, including individuals of both sexes. Intrinsic
characteristics had no influence on hierarchical structure, with the exception of
the male in the highest hierarchical position, which had a markedly larger body
than all other group members. Thus, the prior-attributes model did not apply to
hierarchical formation of S. collinsi in captivity. Only the frequency of
agonistic behavior of males correlated with their hierarchical position, and they
differed from all other group members in their more aggressive behavior. The
steepness between adjacent positions along the dominance gradient was significant
only between the dominant male and the next individual in the group, with a
smooth gradient between the other positions in the rank. As the access to
resources is directly related to hierarchical dominance, a smooth dominance
gradient is to be expected in species that form very large groups, such as wild
Saimiri populations.
PMID- 29948417
TI - Cost Effectiveness of Cytoreductive Surgery and Hyperthermic Intraperitoneal
Chemotherapy for Management of Colorectal Peritoneal Carcinomatosis.
AB - BACKGROUND: Peritoneal carcinomatosis from colorectal cancer is a stage 4 disease
for which palliative chemotherapy has traditionally been considered the mainstay
of treatment. Since the development of cytoreductive surgery (CRS) and
hyperthermic intraperitoneal chemotherapy (HIPEC) by Sugarbaker, this combined
method treatment has resulted in improved survival outcomes with acceptable
morbidity for selected patients with peritoneal carcinomatosis. This study
examined the cost effectiveness of CRS and HIPEC compared with palliative
chemotherapy for patients with peritoneal carcinomatosis from colorectal cancer
within the context of the Singaporean health care system. METHODS: A
retrospective review of patients with peritoneal carcinomatosis from
histologically proven colorectal cancer treated at the National Cancer Centre
Singapore (NCCS) was conducted. RESULTS: The average cost of CRS and HIPEC per
patient was S$83,680.26, and the median overall survival period was 47 months.
The calculated cost per life year attained for a patient who underwent CRS and
HIPEC was S$21,365.19 per life year. In comparison, the average cost of
palliative chemotherapy was S$44,478.87, with a median overall survival of 9
months, and the calculated cost per life year attained for a patient in this
treatment group was S$59,305.16 per life year. CONCLUSION: The findings show that
CRS and HIPEC results in prolonged survival for selected patients with colorectal
peritoneal carcinomatosis and a lower cost per life year attained than for the
traditionally used palliative chemotherapy. It should logically be the preferred
treatment of choice for selected patients with colorectal peritoneal metastasis.
PMID- 29948419
TI - Current Management and Future Opportunities for Peritoneal Metastases.
PMID- 29948418
TI - Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary
Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III
Trial.
AB - BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant
patches reduced lymphatic drainage after various lymphadenectomy procedures. Our
goal was to investigate the impact of these patches on drainage after axillary
dissection for breast cancer. METHODS: In a phase III superiority trial, we
randomized patients undergoing breast-conserving surgery at 14 Swiss sites to
receive versus not receive three large TachoSil(r) patches in the dissected
axilla. Axillary drains were inserted in all patients. Patients and investigators
assessing outcomes were blinded to group assignment. The primary endpoint was
total volume of drainage. RESULTS: Between March 2015 and December 2016, 142
patients were randomized (72 with TachoSil(r) and 70 without). Mean total volume
of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895
ml]. Application of TachoSil(r) did not significantly reduce the total volume of
axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A
total of eight secondary endpoints related to drainage, morbidity, and quality of
life were not improved by use of TachoSil(r). The mean total cost per patient did
not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625
35,880) with TachoSil(r) and 33,365 Swiss Francs (95% CI 31,771-34,961) without,
p = 0.584]. In the TachoSil(r) group, length of stay was longer (MD 1 day, 95% CI
0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter
difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p
= 0.2]. CONCLUSIONS: TachoSil(r) reduced drainage after axillary dissection for
breast cancer neither significantly nor relevantly.
PMID- 29948420
TI - Outcome of Patients Treated Within and Outside a Randomized Clinical Trial on
Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: Extrapolation
of a Randomized Clinical Trial (CROSS).
AB - BACKGROUND: Randomized clinical trials (RCTs) can provide a high level of
evidence for medical decision making, but it is unclear if the results apply to
patients treated outside such trials. OBJECTIVE: The aim of this study was to
retrospectively compare outcomes of patients with esophageal cancer treated
within and outside an RCT. METHODS: All patients receiving neoadjuvant
chemoradiotherapy (nCRT) plus surgery for esophageal cancer between 2002 and 2008
(ChemoRadiotherapy for Esophageal cancer followed by Surgery Study [CROSS]
cohort) who participated in multicenter, phase II-III trials were compared with
patients who underwent the same treatment outside the trial between 2008 and 2013
(post-CROSS cohort). The differences between these cohorts were analyzed using t
tests, while logistic regression models were used to evaluate adverse events.
Overall and disease-free survival were calculated using the Kaplan-Meier method
and Cox regression analyses. RESULTS: A total of 208 CROSS patients and 173 post
CROSS patients were included in this study. Patients from the post-CROSS cohort
were older, had more co morbidities, and had poorer performance status. Clinical
N stage, but not cT stage, was worse in the post-CROSS cohort. There were no
statistically significant differences in adverse events (pulmonary, cardiac, or
anastomotic complications) or survival between the comparison cohorts.
CONCLUSION: The outcomes of patients treated with nCRT plus esophagectomy for
cancer have a high external consistency and can be extrapolated to the daily
practice of physicians involved in the treatment and care of esophageal cancer
patients.
PMID- 29948421
TI - Circulating Interleukin-6 is Associated with Prognosis and Genetic Polymorphisms
of MIR608 in Patients with Esophageal Squamous Cell Carcinoma.
AB - BACKGROUND: No effective targeted therapy exists for esophageal squamous cell
carcinoma (ESCC), the major cell type of esophageal cancer. The pleiotropic
cytokine interleukin (IL)-6 is associated with adverse prognosis of some cancers,
and the open reading frame of IL-6 contains an miR-608 microRNA-targeted site. We
investigated the correlation of circulating IL-6 levels with prognosis and with
the mir608:rs4919510 genetic polymorphism in ESCC. METHODS: A total of 213
patients with primary ESCC were enrolled. Plasma IL-6 levels of ESCC patients
were analyzed by enzyme-linked immunosorbent assay (ELISA). The patients'
genotypes of mir608:rs4919510 were analyzed using the MassARRAY system, and
functional assays were performed by transient overexpression in cells. The
cytotoxicity of IL-6 signaling blockers in ESCC cells was analyzed by MTT assay.
RESULTS: We found that plasma IL-6 levels significantly correlated with overall
survival (p = 0.019), disease recurrence (p = 0.003), and postoperative
complications (p =0.002). Patients with the GG genotype of mir608:rs4919510 had a
4.56-fold increased risk of high expression of IL-6 compared with patients with
the CC genotype (odds ratio 4.56, 95% confidence interval 1.87-11.09; p =0.001).
Transient overexpression of the miR-608 C (miR-608_C) and G variants (miR-608_G)
in cancer cells revealed that the miR-608_G variant was less efficient in
regulating the expression of IL-6 compared with miR-608_C. Finally, the IL-6
signaling blocker ruxolitinib exhibited effective cytotoxicity in ESCC cells.
CONCLUSIONS: The results of this study provide a novel direction for a biomarker
based targeted therapy for ESCC.
PMID- 29948423
TI - Robotic-Assisted Surgery for Upper Tract Urothelial Carcinoma: A Comparative
Survival Analysis.
AB - BACKGROUND: We performed a comparative survival analysis of patients undergoing
robotic-assisted versus laparoscopic or open surgery for upper tract urothelial
carcinoma (UTUC). MATERIALS AND METHODS: Patients diagnosed with non-metastatic
UTUC undergoing removal of the kidney and/or ureter were identified using
Medicare-linked Surveillance, Epidemiology, and End Results Program data (2004
2013). Patients aged 65-85 years were categorized based on surgical approach
(open, laparoscopic, or robotic-assisted). Kaplan-Meier methods were used to
determine survival (overall and cancer-specific) and intravesical recurrence
rates, the former using a propensity score-weighted model. Independent predictors
of survival were determined using multivariable Cox proportional hazards
regression analysis. RESULTS: We identified a total of 3801 patients meeting the
final inclusion criteria: open (n = 1862), laparoscopic (n = 1624), and robotic
(n = 315). Robotic surgery was associated with the shortest length of hospital
stay (p < 0.001) but highest in-hospital charges (p < 0.001), with no difference
in readmission rates (p = 0.964). No difference was found in overall or cancer
specific survival in the robotic cohort when compared with open or laparoscopic
surgery. In addition, no difference in the rate of intravesical recurrence was
noted in robotic-assisted laparoscopy compared with the other groups. The sole
predictor of improved survival was extent of lymphadenectomy, which was highest
in the robotic cohort. CONCLUSIONS: Using a large, population-based cancer
database, there was no survival difference when a robotic-assisted approach was
utilized in patients undergoing surgery for UTUC. These findings are important
with the increased use of robotic surgery in the management of UTUC.
PMID- 29948424
TI - Minimally Invasive Surgery for Retroperitoneal Sarcoma: Just Because We Can Does
Not Mean We Should.
PMID- 29948422
TI - Preoperative Circulating Tumor DNA in Patients with Peritoneal Carcinomatosis is
an Independent Predictor of Progression-Free Survival.
AB - BACKGROUND: Next-generation sequencing (NGS) is a useful tool for detecting
genomic alterations in circulating tumor DNA (ctDNA). To date, most ctDNA tests
have been performed on patients with widely metastatic disease. Patients with
peritoneal carcinomatosis (metastases) present unique prognostic and therapeutic
challenges. We therefore explored preoperative ctDNA in patients with peritoneal
metastases undergoing surgery. METHODS: Patients referred for surgical resection
of peritoneal metastases underwent preoperative blood-derived ctDNA analysis
(clinical-grade NGS [68-73 genes]). ctDNA was quantified as the percentage of
altered circulating cell-free DNA (% cfDNA). RESULTS: Eighty patients had ctDNA
testing: 46 (57.5%) women; median age 55.5 years. The following diagnoses were
included: 59 patients (73.8%), appendix cancer; 11 (13.8%), colorectal; five
(6.3%), peritoneal mesothelioma; two (2.5%), small bowel; one (1.3%) each of
cholangiocarcinoma, ovarian, and testicular cancer. Thirty-one patients (38.8%)
had detectable preoperative ctDNA alterations, most frequently in the following
genes: TP53 (25.8% of all alterations detected) and KRAS (11.3%). Among 15
patients with tissue DNA NGS, 33.3% also had ctDNA alterations (overall
concordance = 96.7%). Patients with high ctDNA quantities (>= 0.25% cfDNA, n =
25) had a shorter progression-free survival (PFS) than those with lower ctDNA
quantities (n = 55; 7.8 vs. 15.0 months; hazard ratio 3.23, 95% confidence
interval 1.43-7.28, p = 0.005 univariate, p = 0.044 multivariate). CONCLUSIONS: A
significant proportion of patients with peritoneal metastases referred for
surgical intervention have detectable ctDNA alterations preoperatively. Patients
with high levels of ctDNA have a worse prognosis independent of histologic grade.
PMID- 29948425
TI - Implications of the Pattern of Disease Recurrence on Survival Following
Pancreatectomy for Pancreatic Ductal Adenocarcinoma.
AB - BACKGROUND: After radical resection of pancreatic ductal adenocarcinoma (PDAC),
approximately 80% of patients will develop disease recurrence. It remains unclear
to what extent the location of recurrence carries prognostic significance.
Additionally, stratifying the pattern of recurrence may lead to a deeper
understanding of the heterogeneous biological behavior of PDAC. OBJECTIVE: The
aim of this study was to characterize the relationship of recurrence patterns
with survival in patients with resected PDAC. METHODS: This single-center cohort
study included patients undergoing pancreatectomy at the Johns Hopkins Hospital
between 2000 and 2013. Exclusion criteria were neoadjuvant therapy and incomplete
follow-up. Sites of first recurrence were stratified into five groups and
survival outcomes were estimated using Kaplan-Meier curves. The association of
specific recurrence locations with overall survival (OS) was analyzed using Cox
proportional-hazards models with and without landmark analysis. RESULTS: Accurate
follow-up data were available for 877 patients, 662 (75.5%) of whom had
documented recurrence at last follow-up. Patients with multiple-site (n = 227,
4.7 months) or liver-only recurrence (n = 166, 7.2 months) had significantly
worse median survival after recurrence when compared with lung- (n = 93) or local
only (n = 158) recurrence (15.4 and 9.7 months, respectively). On multivariable
analysis, the unique recurrence patterns had variable predictive values for OS.
Landmark analyses, with landmarks set at 12, 18, and 24 months, confirmed these
findings. CONCLUSIONS: This study demonstrates that specific patterns of PDAC
recurrence result in different survival outcomes. Furthermore, distinct first
recurrence locations have unique independent predictive values for OS, which
could help with prognostic stratification and decisions regarding treatment after
the diagnosis of recurrence.
PMID- 29948427
TI - Professional Burnout of Psychiatrists in a Veterans Health Administration:
Exploring the Role of the Organizational Treatment.
AB - Psychiatrists in the Veterans Health Administration (VHA) are susceptible to
professional burnout due to the unique needs of veterans combined with high
organizational demands. The current study examined the mediating role of
organizational factors in the direct relationship between providing primarily
pharmacological intervention and professional burnout. Data from 125 VHA
psychiatrists revealed that fair treatment by superiors and sufficient resources
independently mediated the direct relationship that the percent of time devoted
to pharmacological intervention had with emotional exhaustion and cynicism.
Psychiatrists who feel unfairly treated and lack sufficient resources reported
more professional burnout. Implications and future directions are discussed.
PMID- 29948426
TI - Presence of growth/differentiation factor-15 cytokine in human follicular fluid,
granulosa cells, and oocytes.
AB - PURPOSE: The purpose of the study was to determine whether the GDF-15 is present
in follicular fluid; to evaluate if there is a relation between follicular and
serum levels of GDF-15 and fertility status of study subjects; and to test
whether granulosa cells, oocytes, or both produce GDF-15. METHODS: This study
used follicular fluid (FF, serum, and oocytes obtained under informed consent
from women undergoing oocyte retrieval for in vitro fertilization. It also used
ovaries from deceased preterm newborns. Collection of FF and blood at the time of
oocyte retrieval, ELISA and western blot were performed to determine levels and
forms of GDF-15. Concentrations of GDF-15 in FF and serum, its expression in
ovarian tissue, and secretion from granulosa cells were analyzed. RESULTS: GDF-15
concentration in FF ranged from 35 to 572 ng/ml, as determined by ELISA. Western
blot analysis revealed the GDF-15 pro-dimer only in FF. Both normal healthy and
cancerous granulosa cells secreted GDF-15 into culture media. Primary oocytes
displayed cytoplasmic GDF-15 positivity in immunostained newborn ovaries, and its
expression was also observed in fully grown human oocytes. CONCLUSIONS: To the
best of our knowledge, this is the first documentation of cytokine GDF-15
presence in follicular fluid. Its concentration was not associated with
donor/patient fertility status. Our data also show that GDF-15 is expressed and
inducible in both normal healthy and cancerous granulosa cells, as well as in
oocytes.
PMID- 29948429
TI - In memoriam Ladislas Robert (1924-2018).
PMID- 29948428
TI - Laboratory of the Neuropsychology and Cognitive Neurosciences Research Center of
Universidad Catolica del Maule, Chile.
AB - The Laboratory of the Neuropsychology and Cognitive Neurosciences Research Center
(CINPSI Neurocog), located in the "Technological Park" building of the Catholic
University of Maule (Universidad Catolica del Maule, UCM) campus in Talca, Chile,
has been established as "Psychology Lab" recently in July, 2016. Our lines of
work include basic and applied research. Among the basic research, we study
executive functions, decision-making, and spatial cognition. In the applied
field, we have studied neuropsychological and neurobehavioral effects of
pesticides exposure, among other interests. One of our aims is to develop
collaboration both national and internationally. It is important to mention that
to date there are only few psychology laboratories and research centers in Chile
involved with the fields of neuropsychology and neurosciences. Thus, this
scientific effort could be a groundbreaking initiative to develop specific
knowledge in this area locally and interculturally through its international
collaborations.
PMID- 29948431
TI - Philosophy of Healthcare Ethics Practice Statements: Quality Attestation and
Beyond.
AB - One element of the American Society for Bioethics and Humanities' recently
piloted quality attestation portfolio for clinical ethics consultants is a
"philosophy of clinical ethics consultation statement" describing the candidate's
approach to clinical ethics consultation. To date, these statements have been
under-explored in the literature, in contrast to philosophy statements in other
fields such as academic teaching. In this article, I argue there is merit in
expanding the content of these statements beyond clinical ethics consultation
alone to describe the author's approach to other important "domains" of
healthcare ethics practice (e.g., organizational policy development/review and
ethics teaching). I also claim such statements have at least three additional
uses outside quality attestation: (1) as a reflective practice learning tool to
increase role clarity among practicing healthcare ethicists and bioethics
fellows; (2) assisting practicing healthcare ethicists in clarifying role
expectations with those they work with; and (3) helping inform developing
professional practice standards.
PMID- 29948432
TI - Impact of mapped EQ-5D utilities on cost-effectiveness analysis: in the case of
dialysis treatments.
AB - OBJECTIVES: This study aimed to evaluate the performance of EQ-5D data mapped
from SF-12 in terms of estimating cost effectiveness in cost-utility analysis
(CUA). The comparability of SF-6D (derived from SF-12) was also assessed.
METHODS: Incremental quality-adjusted life years (QALYs) and incremental cost
effectiveness ratios (ICERs) were calculated based on two Markov models assessing
the cost effectiveness of haemodialysis (HD) and peritoneal dialysis (PD) using
utility values based on EQ-5D-5L, EQ-5D using three direct-mapping algorithms and
two response-mapping algorithms (mEQ-5D), and SF-6D. Bootstrap method was used to
estimate the 95% confidence interval (percentile method) of incremental QALYs and
ICERs with 1000 replications for the utilities. RESULTS: In both models, compared
to the observed EQ-5D values, mEQ-5D values expressed much lower incremental
QALYs (range - 14.9 to - 33.2%) and much higher ICERs (range 17.5 to 49.7%). SF
6D also estimated lower incremental QALYs (- 29.0 and - 14.9%) and higher ICERs
(40.9 and 17.5%) than did the observed EQ-5D. The 95% confidence interval of
incremental QALYs and ICERs confirmed the lower incremental QALYs and higher
ICERs estimated using mEQ-5D and SF-6D. CONCLUSION: Compared to observed EQ-5D,
EQ-5D mapped from SF-12 and SF-6D would under-estimate the QALYs gained in cost
utility analysis and thus lead to higher ICERs. It would be more sensible to
conduct CUA studies using directly collected EQ-5D data and to designate one
single preference-based measure as reference case in a jurisdiction to achieve
consistency in healthcare decision-making.
PMID- 29948430
TI - Effectiveness of real-time PCR for diagnosis and prognosis of varicella-zoster
virus keratitis.
AB - PURPOSE: To determine the efficacy of real-time PCR for the diagnosis and
prognosis of varicella-zoster virus (VZV) keratitis. STUDY DESIGN: Retrospective
case series. METHODS: Patients: 545 consecutive patients with keratitis were
examined to quantify copy numbers of VZV DNA by real-time PCR. Association of
copy numbers of VZV DNA to clinical signs and disease course was assessed by
logistic regression analysis and Cox proportional hazard model. RESULTS: Of the
545 eyes, 38 (6.9%) were diagnosed as VZV keratitis. The median copy number of
the VZV DNA was 104.19 copies; this number was significantly associated with
diagnosis of VZV keratitis with the highest odds ratio of 3390 (for median copy)
compared to the clinical signs. The diagnostic accuracy of the VZV DNA copy
indicated good diagnostic value of area under the curve (0.92) by receiver
operating characteristic analysis, and detection of unrelated VZV DNA from the
cornea was very rare (0.2%). When the VZV DNA copy and clinical signs were
assessed for association with the disease course of herpes zoster ophthalmicus,
the disease duration was significantly prolonged in VZV keratitis cases with
higher numbers of VZV DNA copies, iritis, and history of recurrences. The amount
of VZV DNA led to a continuous risk of prolonged disease duration until the
ocular inflammation subsided (hazard ratio 0.17, 95% CI 0.07-0.42, for median
copies). CONCLUSIONS: Higher VZV DNA copy numbers are associated with the
refractoriness of VZV keratitis, and its evaluation may be a useful way to
clinically diagnose and manage VZV keratitis.
PMID- 29948433
TI - A Short-Term Population Model of the Suicide Risk: The Case of Spain.
AB - A relevant proportion of deaths by suicide have been attributed to other causes
that produce the number of suicides remains hidden. The existence of a hidden
number of cases is explained by the nature of the problem. Problems like this
involve violence, and produce fear and social shame in victims' families. The
existence of violence, fear and social shame experienced by victims favours a
considerable number of suicides, identified as accidents or natural deaths. This
paper proposes a short time discrete compartmental mathematical model to measure
the suicidal risk for the case of Spain. The compartment model classifies and
quantifies the amount of the Spanish population within the age intervals (16, 78)
by their degree of suicide risk and their changes over time. Intercompartmental
transits are due to the combination of quantitative and qualitative factors.
Results are computed and simulations are performed to analyze the sensitivity of
the model under uncertain coefficients.
PMID- 29948434
TI - Thalassorhabdus aurantiaca gen. nov., sp. nov., a new member of the family
Flavobacteriaceae isolated from seawater in South Korea.
AB - A novel Gram-negative, orange pigmented, strictly aerobic bacterium, designated
strain IP9T, was isolated from seawater at the sea shore of Incheon Eulwang-ri
beach, South Korea. Cells of strain IP9T were observed to be straight or slightly
curved rods and colonies to be round and convex. Strain IP9T was found to be
catalase and oxidase positive, and non-motile. Growth was observed in the
temperature range of 10-37 degrees C (optimum at 30 degrees C), pH range of 6
10 (optimum at pH 7-8) and salt concentration range of 0-7% (w/v) NaCl (optimum
at 0-1%). On the basis of 16S rRNA gene sequence similarity and phylogenetic
analysis, strain IP9T was found to be related to the members of the family
Flavobacteriaceae, being closely related to Hwangdonia seohaensis KCTC 32177T
(95.3% sequence similarity). The DNA G + C content of the novel strain was
determined to be 39.1 mol%. The major polar lipids were found to be
phosphatidylethanolamine, three unidentified aminoglycolipids and two
unidentified glycolipids. The major fatty acids (> 10%) were identified as iso
C15:0 and iso-C17:0 3-OH. The predominant quinone was found to be menaquinone 6
(MK-6). Based on the biochemical, phylogenetic and physiological data, we
conclude that strain IP9T (= KCTC 52523T = JCM 31732T) represents the type
species of a novel genus of the family Flavobacteriaceae for which the name
Thalassorhabdus aurantiaca gen. nov., sp. nov. is proposed.
PMID- 29948435
TI - Cadophora margaritata sp. nov. and other fungi associated with the longhorn
beetles Anoplophora glabripennis and Saperda carcharias in Finland.
AB - Symbiosis with microbes is crucial for survival and development of wood
inhabiting longhorn beetles (Coleoptera: Cerambycidae). Thus, knowledge of the
endemic fungal associates of insects would facilitate risk assessment in cases
where a new invasive pest occupies the same ecological niche. However, the
diversity of fungi associated with insects remains poorly understood. The aim of
this study was to investigate fungi associated with the native large poplar
longhorn beetle (Saperda carcharias) and the recently introduced Asian longhorn
beetle (Anoplophora glabripennis) infesting hardwood trees in Finland. We studied
the cultivable fungal associates obtained from Populus tremula colonised by S.
carcharias, and Betula pendula and Salix caprea infested by A. glabripennis, and
compared these to the samples collected from intact wood material. This study
detected a number of plant pathogenic and saprotrophic fungi, and species with
known potential for enzymatic degradation of wood components. Phylogenetic
analyses of the most commonly encountered fungi isolated from the longhorn
beetles revealed an association with fungi residing in the Cadophora-Mollisia
species complex. A commonly encountered fungus was Cadophora spadicis, a recently
described fungus associated with wood-decay. In addition, a novel species of
Cadophora, for which the name Cadophora margaritata sp. nov. is provided, was
isolated from the colonised wood.
PMID- 29948436
TI - Laterality Classification of Fundus Images Using Interpretable Deep Neural
Network.
AB - In this paper, we aimed to understand and analyze the outputs of a convolutional
neural network model that classifies the laterality of fundus images. Our model
not only automatizes the classification process, which results in reducing the
labors of clinicians, but also highlights the key regions in the image and
evaluates the uncertainty for the decision with proper analytic tools. Our model
was trained and tested with 25,911 fundus images (43.4% of macula-centered images
and 28.3% each of superior and nasal retinal fundus images). Also, activation
maps were generated to mark important regions in the image for the
classification. Then, uncertainties were quantified to support explanations as to
why certain images were incorrectly classified under the proposed model. Our
model achieved a mean training accuracy of 99%, which is comparable to the
performance of clinicians. Strong activations were detected at the location of
optic disc and retinal blood vessels around the disc, which matches to the
regions that clinicians attend when deciding the laterality. Uncertainty analysis
discovered that misclassified images tend to accompany with high prediction
uncertainties and are likely ungradable. We believe that visualization of
informative regions and the estimation of uncertainty, along with presentation of
the prediction result, would enhance the interpretability of neural network
models in a way that clinicians can be benefitted from using the automatic
classification system.
PMID- 29948437
TI - Evaluation of the Olweus Bully Prevention Program in an Urban School System in
the USA.
AB - This study evaluated the Olweus Bully Prevention Program (OBPP) in urban middle
schools serving a mostly African American student population. Participants were
1791 students from three communities with high rates of crime and poverty. We
evaluated the impact of the OBPP using a multiple-baseline experimental design in
which we randomized the order and timing of intervention activities across three
schools. We assessed the frequency of violence and victimization using self
report and teachers' ratings of students collected every 3 months over 5 years.
Initiation of the OBPP was associated with reductions in teachers' ratings of
students' frequency of aggression, with effects emerging in different years of
implementation for different forms of aggression. Whereas reductions in teachers'
ratings of students' verbal and relational aggression and victimization were
evident during the second implementation year, reductions in physical aggression
did not appear until the third year. Effects were consistent across gender and
schools, with variability across grades for relational and verbal aggression and
victimization. In contrast, there were no intervention effects on students'
reports of their behavior. Positive outcomes for teachers', but not students'
ratings, suggest the intervention's effects may have been limited to the school
context. Variation in when effects emerged across outcomes suggests that changes
in physical aggression may require more sustained intervention efforts. The
intervention was also associated with increases in teachers' concerns about
school safety problems, which may indicate that teachers were more attuned to
recognizing problem behaviors following exposure to the OBPP.
PMID- 29948438
TI - Invasive Fungal Infection Caused by Exophiala dermatitidis in a Patient After
Lung Transplantation: Case Report and Literature Review.
AB - This report describes a case of invasive Exophiala dermatitidis infection after
double lung transplantation in a 76-year-old man. After thoracotomy, the
patient's wound showed dehiscence with purulent secretion. The black yeast was
isolated from cultures taken from the wound, and species identification was
confirmed by sequence analysis of the internal transcribed spacer (ITS-S2)
region. The results of the susceptibility testing showed voriconazole as the most
active drug. Despite adaptation of the antifungal therapy the clinical condition
worsened, and the patient died. In addition, we evaluated the fungicidal activity
of antiseptics towards E. dermatitidis and aimed to provide a brief literature
review of previously reported infections caused by this rare fungus. To the best
of our knowledge, this is the first report of a rapidly progressing invasive
fungal infection with E. dermatitidis originating from a colonized wound after
lung transplantation.
PMID- 29948439
TI - Segmental isotope labelling and solid-state NMR of a 12 * 59 kDa motor protein:
identification of structural variability.
AB - Segmental isotope labelling enables the NMR study of an individual domain within
a multidomain protein, but still in the context of the entire full-length
protein. Compared to the fully labelled protein, spectral overlap can be greatly
reduced. We here describe segmental labelling of the (double-) hexameric DnaB
helicase from Helicobacter pylori using a ligation approach. Solid-state spectra
demonstrate that the ligated protein has the same structure and structural order
as the directly expressed full-length protein. We uniformly 13C/15N labeled the N
terminal domain (147 residues) of the protein, while the C-terminal domain (311
residues) remained in natural abundance. The reduced signal overlap in solid
state NMR spectra allowed to identify structural "hotspots" for which the
structure of the N-terminal domain in the context of the oligomeric full-length
protein differs from the one in the isolated form. They are located near the
linker between the two domains, in an alpha-helical hairpin.
PMID- 29948441
TI - Is medium dose of cyclosporine A effective in treatment of children with steroid
dependent nephrotic syndrome with reduction in corticosteroids dose consumption?
PMID- 29948440
TI - Insight into human insulin aggregation revisited using NMR derived translational
diffusion parameters.
AB - The NMR derived translational diffusion coefficients were performed on unlabeled
and uniformly labeled 13C,15N human insulin in water, both in neat, with zinc
ions only, and in pharmaceutical formulation, containing only m-cresol as
phenolic ligand, glycerol and zinc ions. The results show the dominant role of
the pH parameter and the concentration on aggregation. The diffusion coefficient
Dav was used for monitoring the overall average state of oligomeric ensemble in
solution. The analysis of the experimental data of diffusion measurements, using
the direct exponential curve resolution algorithm (DECRA) allows suggesting the
two main components of the oligomeric ensemble. The 3D HSQC-iDOSY, (diffusion
ordered HSQC) experiments performed on 13C, 15N-fully labeled insulin at the two
pH values, 4 and 7.5, allow for the first time a more detailed experimental
observation of individual components in the ensemble. The discussion involves
earlier static and dynamic laser light scattering experiments and recent NMR
derived translational diffusion results. The results bring new informations
concerning the preparation of pharmaceutical formulation and in particular a role
of Zn2+ ions. They also will enable better understanding and unifying the results
of studies on insulin misfolding effects performed in solution by diverse
physicochemical methods at different pH and concentration.
PMID- 29948442
TI - The first year results of mizoribine/tacrolimus-based multitarget treatment for
consecutive patients with lupus nephritis.
AB - BACKGROUND: Despite the high efficacy of mycophenolate mofetil (MMF)/tacrolimus
based multitarget treatment, risks of infections are a matter of concern. In the
present study, we clarified the potential of multitarget therapy using mizoribine
opposed to MMF. METHODS: A total of 36 patients with biopsy-proven lupus
nephritis were treated with mizoribine, tacrolimus, and glucocorticoids and then
retrospectively evaluated. To determine the efficacy, proteinuria remission (<=
0.2 g/day), complete remission (Liu et al. in Ann Intern Med 162:18-26, 2015) and
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) remission rates, and
the prednisolone dose at months 6 and 12 were evaluated. The associations between
serum mizoribine/tacrolimus levels and clinical parameters were investigated. To
assess safety, adverse events were inspected. RESULTS: All patients could
continue the original treatment regimen without withdrawal or exacerbations
through month 12. At month 6, the proteinuria remission, complete remission,
SLEDAI remission rates, and prednisolone dose were 69, 53, 36%, and 12.1 mg/day,
respectively, whereas the values at 12 months were 92, 67, 50%, and 8.8 mg/day,
respectively. The treatment was efficacious for every histologic type of
nephritis and non-renal manifestations of SLE. Excluding one patient who was
hospitalized due to upper respiratory tract infection, serious infections,
including pneumonia and cytomegalovirus disease, were not observed. Higher trough
tacrolimus levels were associated with normalization of complement, whereas
higher peak mizoribine levels with prevention of cytomegalovirus viremia.
CONCLUSIONS: Our results suggest that multitarget therapy using mizoribine
opposed to MMF is highly safe and effective through 12 months. The therapy may
enable faster dose reduction of concomitant glucocorticoids.
PMID- 29948443
TI - GFR-estimation by serum creatinine during glucocorticosteroid therapy.
AB - BACKGROUND: While glucocorticosteroids (GCS) are widely used in patients with
kidney disease, little is known about their effect on serum creatinine, the most
commonly used endogenous marker of kidney function. METHODS: We assessed the
effect of GCS on the relationship between estimated GFR using the Schwartz
equation (eGFR) and measured GFR using a single-injection inulin clearance (Cin)
in children both in a paired analysis and a cross-sectional study. Primary
outcome variable was the difference between eGFR and Cin (DeltaGFR) in a paired
analysis involving 22 patients during and off GCS treatment (mean GFR 103.8
ml/min/1.73 m2, mean prednisone dose 34.8 mg/m2/day). In a cross-sectional
analysis in 42 patients receiving GCS (mean dose of 25.7 mg/m2/day), a dose
dependent effect was explored using univariate and multivariate linear regression
of various variables including GCS dosage with serum creatinine as dependent
variable. RESULTS: The paired analysis showed no significant difference in
DeltaGFR with or without GCS [- 23 (SD 53) vs. - 9 (SD 41) ml/min/1.73 m2, p =
0.203]. Stepwise multivariate linear regression analysis showed a significant
correlation between age and Cin, while GCS dose was not related to serum
creatinine. CONCLUSION: GCS use had no significant effect on serum creatinine as
a marker for kidney function in a mixed population of renal outpatient clinic
children.
PMID- 29948444
TI - Effect of essential amino acid ketoanalogues and protein restriction diet on
morphogenetic proteins (FGF-23 and Klotho) in 3b-4 stages chronic kidney disease
patients: a randomized pilot study.
AB - BACKGROUND: A low protein diet (LPD) with essential amino acid ketoanalogue
supplementation (KA) may contribute in improving of chronic kidney disease (CKD),
while the exact mechanisms of KA's effect are not established yet. We have
conducted a prospective, randomized, controlled comparative study of LPD + KA and
LPD alone in relation to serum Klotho, FGF-23 levels in CKD patients. METHODS: 79
non-diabetic CKD 3b-4 stage patients, compliant with LPD diet (0.6 g/kg of body
weight/day), had been selected. The patients were randomized into two groups. The
first group (42 patients) received LPD + KA. The second group (37 patients)
continued the LRD alone. In addition to routine tests, serum Klotho, FGF-23
levels, as well as bioimpedance analysis, sphygmography (stiffness (augmentation)
indices (AI), central (aortal) blood pressure) with a "SphygmaCor" device;
echocardiography (valvular calcification score (VCS) and LVMMI), were performed.
RESULTS: There were body mass indices' decrease (p = 0.046), including muscle
body mass in men (p = 0.027) and woman (p = 0.044) in the LPD group to the end of
study (14th month). In addition, lower FGF-23 (p = 0.029), and higher sKlotho (p
= 0.037) were detected in the LPD + KA group compared to the LPD one. The
increase in AI (p = 0.034), VCS (p = 0.048), and LVMMI (p = 0.023) was detected
more often in the LPD group at the end of study. CONCLUSION: LPD + KA provides
support for nutrition status and contributes to more efficient correction of FGF
23 and Klotho abnormalities that may result in cardiovascular calcification and
cardiac remodeling decreasing in CKD. At the same time, a prolonged LPD alone may
lead to malnutrition.
PMID- 29948445
TI - Long-term outcomes in acute kidney injury patients who underwent continuous renal
replacement therapy: a single-center experience.
AB - INTRODUCTION: Acute kidney injury (AKI) requiring continuous renal replacement
therapy (CRRT) is the most severe form of AKI associated with poor short- and
long-term patient outcomes. The aim of this study was to evaluate the variables
associated with long-term patient survival in our clinic. METHODS: This was a
single-center retrospective study with AKI survivors who received CRRT from March
2011 to February 2015. During the study period, all consecutive AKI survivors who
underwent CRRT were included. Patients on maintenance dialysis prior to CRRT were
excluded. Data were collected by reviewing the patients' medical charts. Long
term follow-up data were gathered through February 2018. RESULTS: A total of 430
patients were included, and 62.8% of the patients were male. The mean age of the
patients was 63.4 +/- 14.6 years. The mean serum creatinine level at the time of
CRRT initiation was 3.5 +/- 2.5 mg/dL. At the time of discharge, the mean eGFR
and serum creatinine levels were 58.4 +/- 46.7 and 1.7 +/- 1.6 mg/dL,
respectively. After 3 years, 44.9% of the patients had survived. When we
investigated the factors associated with long-term patient mortality, a longer
stay in the ICU [OR 1.034 (1.016-1.053), p < 0.001], a history of cancer [OR
3.830 (1.037-3.308), p = 0.037], a prolonged prothrombin time [OR 1.852 (1.037
3.308), p = 0.037] and a lower eGFR at the time of discharge [OR 0.988 (0.982
0.995), p = 0.001] were independently associated with long-term patient
mortality. CONCLUSION: Our study demonstrates that long-term mortality after CRRT
is associated with longer ICU stays and lower eGFRs at the time of hospital
discharge. Our data imply the importance of renal recovery for long-term survival
of AKI patients treated with CRRT.
PMID- 29948446
TI - Effect of peritoneal dialysis vs. haemodialysis on respiratory mechanics in acute
kidney injury patients.
AB - BACKGROUND: Peritoneal dialysis (PD) and hemodialysis (HD) are options for the
treatment of acute kidney injury (AKI) patients. The aim of this study was to
compare the effects of PD and daily HD on respiratory mechanics of AKI patients
undergoing invasive mechanical ventilation (IMV). METHODS: A prospective cohort
study evaluated 154 patients, 37 on continuous PD and 94 on HD. Respiratory
mechanics parameters such as pulmonary static compliance (Psc) and resistance of
the respiratory system (Rsr) and oxygenation index (OI) were assessed for 3 days.
Patients were evaluated at moments 1, 2 and 3 (pre- and post-dialysis). RESULTS:
The initial clinical parameters were similar in the two groups, except the age
that was higher in continuous PD group (70.8 +/- 11.6 vs. 60 +/- 15.8; p <
0.0001). In both groups, Psc increased significantly, with no difference between
the two groups-pre-dialysis (continuous PD 40 +/- 17.4, 42.8 +/- 17.2, 48 +/- 19;
HD 39.1 +/- 21.3, 39. 5 +/- 18.9, 45.2 +/- 21) and post-dialysis (continuous PD
42.8 +/- 7.2, 48 +/- 19, 57.1 +/- 18.3; HD 42 +/- 19, 45 +/- 18.5, 56 +/- 24.8).
Rsr remained stable among patients on continuous PD (pre-dialysis 10.4 +/- 5.1,
13.3 +/- 7.7, 13.5 +/- 10.3, post-dialysis 13.3 +/- 7.7, 13.5 +/- 10.3, 11.1 +/-
5.9) and decreased among HD patients (pre-dialysis 10.4 +/- 5.1, 10.4 +/- 5.1,
10.4 +/- 5, 1, post-dialysis 10.5 +/- 6.8, 10 +/- 4.9, 8.9 +/- 4.2). There was
difference in Rsr between the two groups at the post-dialysis moments 1 and 2 (p
= 0.03). OI increased in both groups (continuous PD 260.7 +/- 119, 252.7 +/-
87.1, 287.3 +/- 88.4; HD 228 +/- 85, 257 +/- 84, 312.1 +/- 111.5, p > 0.05),
although there was no difference between them. CONCLUSION: AKI patients
undergoing IMV and HD or PD had improvement in the mechanical ventilation and
oxygenation, with no difference between the two groups.
PMID- 29948447
TI - Endocrine-disrupting chemicals in aquatic environment: what are the risks for
fish gametes?
AB - Over the past 25 years, extensive research in vertebrate species has identified
several genomic pathways altered by exposures to anthropogenic chemicals with
hormone-like activity mediated by their interaction with nuclear receptors. In
addition, many pollutants have been shown to interfere with non-genomic (non
classical) pathways, but this mechanism of endocrine disruption is still poorly
understood. Recently, the number of publications describing the effects of
Endocrine disrupting chemicals (EDCs) on fish reproduction, focusing on the
deregulation of the hypothalamus-pituitary-gonadal axis as well as on gamete
quality, significantly increased. Depending on their ability to mimic endogenous
hormones, the may differently affect male or female reproductive physiology.
Inhibition of gametogenesis, development of intersex gonads, alteration of the
gonadosomatic index, and decreased fertility rate have been largely documented.
In males, alterations of sperm density, motility, and fertility have been
observed in several wild species. Similar detrimental effects were described in
females, including negative outcomes on oocyte growth and maturation plus the
occurrence of apoptotic/autophagic processes. These pathways may affect gamete
viability considered as one of the major indicators of reproductive endocrine
disruption. Pollutants act also at DNA level producing DNA mutations and changes
in epigenetic pathways inducing specific mechanisms of toxicity and/or aberrant
cellular responses that may affect subsequent generation(s) through the germline.
In conclusion, this review summarizes the effects caused by EDC exposure on fish
reproduction, focusing on gametogenesis, giving a general overview of the
different aspects dealing with this issue, from morphological alteration,
deregulation of steroidogenesis, hormonal synthesis, and occurrence of epigenetic
process.
PMID- 29948449
TI - Low-level parental mosaicism in an apparent de novo case of Peutz-Jeghers
syndrome.
AB - We report the case of a female found to have mosaicism for mutation in the STK11
gene, with the mutant allele expressed in her gametes, evident by her affected
offspring, and in her gastrointestinal tract demonstrated on an excised polyp
analysed for diagnosis. Mosaicism for Peutz-Jeghers syndrome (PJS) has been
reported in a small number of cases previously but a clinical presentation such
as this has not previously been described. This finding of mosaicism was several
years after initial investigations failed to identify the same STK11 mutation in
this woman whose son was diagnosed with PJS at a young age. This case highlights
the importance of considering mosaicism as an explanation for apparent de novo
cases of PJS syndrome. It also has implications for genetic counselling,
predictive testing and cancer screening.
PMID- 29948448
TI - Transcriptome analysis demonstrates that long noncoding RNA is involved in the
hypoxic response in Larimichthys crocea.
AB - The large yellow croaker (Larimichthys crocea) has low hypoxia tolerance compared
with other fish species, and the mRNA levels of hypoxia-inducible factor (HIF)
1alpha in its brain do not change markedly under hypoxic conditions. In this
study, we investigated noncoding transcription in the hypoxic response mechanism
of L. crocea. We generated a catalog of long noncoding RNAs (lncRNAs) from the
brain of L. crocea individuals under hypoxic stress, investigated lncRNA
expression patterns, and analyzed the HIF signaling pathway by RNA sequencing.
Prolyl hydroxylase domain 2 (PHD2) expression significantly increased after 6 and
12 h of hypoxia, and a lncRNA (Linc_06633.1) was found in the upstream, antisense
region of PHD2. Linc_06633.1 may be an important regulator that promotes PDH2
expression under hypoxia in L. crocea, and we constructed a regulatory profile of
L. crocea under hypoxic conditions. To the best of our knowledge, it is the first
study that has been conducted on hypoxia signaling pathway regulation by lncRNAs
in L. crocea and elucidates the role played by lncRNAs in the regulation of the
hypoxia stress response in teleost fish.
PMID- 29948450
TI - Fibrotomy with diode laser (980 nm) and habit correlation in oral submucous
fibrosis: a report of 30 cases.
AB - To evaluate the efficacy of laser fibrotomy in patients with oral submucous
fibrosis (OSMF) and also to correlate the habit variables causing OSMF. Thirty
patients diagnosed clinically and histopathologically with OSMF were included in
the study. Laser fibrotomy was done under local anesthesia using Zolar diode
laser (980 nm frequency) at 2-W power in contact mode with fibro-optic cutting
tip. The patients were advised to practice mouth-opening exercises rigorously,
and topical corticosteroid was given for burning sensation and pain for 6 months.
Pre- and post-treatment comparison of mouth opening, burning sensation, tongue
protrusion, and cheek flexibility was analyzed after a follow-up period of 9
months. After a follow-up period of 9 months from the surgical intervention, the
mean value of difference in pre- and post-treatment of VAS score, mouth opening,
and tongue protrusion was found to be 3.3 +/- 2.1, 7.7 +/- 5.1, 1.6 +/- 2.7, and
0.38 +/- 0.61 respectively. Using the Wilcoxon signed rank test, all the above
difference in mean was found to be significant with p value < 0.05. With above
suggested significant results, lasers can provide an alternative and better means
for surgical fibrotomy, relieving trismus in moderate OSMF as they are minimally
invasive, cause less hemorrhage, and have faster healing and minimal surgical
site scaring and relapse.
PMID- 29948451
TI - A novel Met-IR-782 near-infrared probe for fluorescent imaging-guided
photothermal therapy in breast cancer.
AB - In this work, a novel photothermal agent based on methionine (Met) was
synthesized, which shows strong absorbance in the near infrared ray (NIR) region
and is available for NIR imaging and in vivo photothermal therapy in a mouse
model. Comparing to free IR-782, the obtained Met modified fluorescent dye (Met
IR-782) exhibited excellent fluorescence stability, preferable photothermal
conversion efficiency under 780 nm laser irradiation and specific targeting to
MCF7 (human breast adenocarcinoma cell line) cells. The fluorescence imaging
ability enabled in situ monitoring of the tumor accumulation of Met-IR-782. The
photothermal cytotoxicity assays in vitro and photothermal therapy treatments in
vivo indicated that Met-IR-782 could efficiently target and suppress the growth
of MCF7 xenograft tumors. Hence, Met-IR-782 is a potential fluorescent agent for
NIR imaging-guided cancer photothermal therapy in clinical application. This work
highlights the prospect of using light absorbing agents for NIR imaging-guided
photothermal therapy.
PMID- 29948453
TI - Effects of laser therapy on patients who underwent rapid maxillary expansion; a
systematic review.
AB - Rapid maxillary expansion (RME) is one of the common treatments of transverse
maxillary deficiency, and low-level laser therapy (LLLT) is one of the
recommended solutions to enhance biological wound or bone healing. This review
article aims to answer the following question: "What are the effects of LLLT, on
patients who underwent surgical or non-surgical RME, in improving clinical
success, wound healing, and bone regeneration?" A search in PubMed, Scopus, Web
of Science, and ProQuest databases was performed, with a focus on the appropriate
key words. Related articles, up to May 2017, were screened, and the full text of
the randomized controlled trials (RCT) were comprehensively read and subjected to
quality assessments. A total of 1804 articles were included after the initial
search. Four RCTs were eligible in randomization and methodology. The applied
wavelength varied from 660 to 830 nm with an output range of 40-100 mW. Also, the
highest exposed energy was 420 J/cm2 and the lowest was 100 J/cm2. The exposure
time differed from 20 to 84 s in each defined point in the palate. Based on the
RCTs available, LLLT is better to be used at initial phase of RME, because it has
some benefits in increasing the rate of bone remodeling.
PMID- 29948454
TI - Diurnal variations and pulpal status: is there a need for FFT besides LDF?
AB - The aim of this article was to investigate the use of laser Doppler flowmetry
(LDF) combined with a fast Fourier transformation (FFT). LDF data in relation to
three different scenarios were evaluated: (a) LDF records of a right central
upper incisor of one patient were used for FFT analysis. These records were
obtained by means of 30 pre-manufactured splints, handled by dentists without any
experience in LDF recording. (b) Diurnal variations in one patient were analysed
with LDF and FFT using 11 splints by one and same experienced investigator at
four specific moments of the day. (c) Pulpal status was analysed using 17
splints. Eleven for a patient, standing as case model and six splints for six
other patients. In this specific group, each patient had one vital and one non
vital central maxillary incisor and was analysed separately by LDF and FFT. The
data of assessment (b) showed diurnal variations on LDF values of almost 80%,
indicating that LDF registration is best performed in the same time period of the
day. Data verification with FFT confirmed the findings without FFT of assessment
(a) and (b). In assessment, (c) FFT demonstrated a clear distinction between a
vital and a non-vital pulp for those cases with one vital tooth and one root
canal treated tooth. In those cases with one vital incisor and the other
traumatised, FFT was undeterminated. Considered that FFT was obtained after LDF
recording and remained undeterminated for a decision in cases with decreasing
pulpal blood flow in time, the added value of FFT in pulpal traumatology was
minimal.
PMID- 29948455
TI - Promotion of wound healing through low-fluence ablative fractional laser
treatment in diabetic mice.
AB - Chronic ulcers are a significant cause of morbidity in diabetic patients, which
can greatly affect a patient's quality of life. While numerous methods have been
developed to promote and enhance wound healing in diabetic patients, a
convenient, effective treatment for diabetic ulcers has yet to be established.
Here, we demonstrate the promotion of wound healing using a low-fluence (2
mJ/spot) ablative fractional laser (AFL) treatment in diabetic mice. Treatment
was shown to confer increases in mRNA expression and in protein abundance of
vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
(bFGF), along with decreases in mRNA expression and protein abundance of
transforming growth factor beta (TGF-beta). Taken together, these results suggest
that low-fluence AFL treatment can be used to promote healing in chronic diabetic
wounds.
PMID- 29948456
TI - Treatment of mucositis with combined 660- and 808-nm-wavelength low-level laser
therapy reduced mucositis grade, pain, and use of analgesics: a parallel, single
blind, two-arm controlled study.
AB - Oral squamous cell carcinoma (OSCC) is the most frequent oral malignant
neoplasia. As consequence of OSCC treatment, oral mucositis (OM) is one of the
most common adverse effects of OSCC treatment. Currently, there is no consensus
for OM treatment. The purpose of the current study was to test the combination of
red and infrared low-level laser therapy (LLLT) for OM treatment. Primary culture
of human fibroblast was performed to identify LLLT dose. After laboratory tests,
a two-arm parallel, single-blind, controlled study was conducted. The two arms
were group 1, both 660- and 808-nm wavelengths (300 J/cm2, 9 J of total energy,
100 mW, spot size 3 mm2), and group 2, only 660-nm wavelength (300 J/cm2, 9 J of
total energy, 100 mW, spot size 3 mm2). Both treatments were performed twice a
week. Group 1 presented a reduction of mucositis grade in comparison to group 2.
Group 1 also presented reduction of analgesics prescription. But no significant
differences between groups 1 and 2 were observed according to the pain scale. In
conclusion, the current study demonstrated that a combination of red and infrared
at a higher dose (300 J/cm2) reduced both oral mucositis grade and analgesics
prescription. The effects of the combination of RT and LLLT are unclear and need
more studies.
PMID- 29948457
TI - Q-switched double frequency Nd:YAG 532-nm nanosecond laser vs. double frequency
Nd:YAG 532-nm picosecond laser for the treatment of solar lentigines in Asians.
AB - Solar lentigines are common pigmentary lesions. Q-switched lasers are effective
treatment options but postinflammatory hyperpigmentation (PIH) is common in
darker skin. The objective of the study is to compare the efficacy and safety in
solar lentigines of Asian skin treated by Q-switched potassium titanyl phosphate
(KTP) 532-nm nanosecond laser vs. KTP 532-nm picosecond laser for the treatment
of solar lentigines in Asians. Thirty patients with at least 2 solar lentigines
on the upper extremities were enrolled. A total of 30 paired lentiginous lesions
were randomly treated with a single treatment of either Q-switched KTP 532-nm
nanosecond laser vs. KTP 532-nm picosecond laser. In terms of efficacy, mean
luminance score was evaluated at baseline, at 6th, and 12th week. Degree of
pigment clearance was assessed by a blinded physician and the patients.
Satisfaction score was rated by patients using visual analogue scale. Adverse
events were also recorded. Twenty-eight patients completed the study. Both lasers
showed significant improvement in mean luminance score from baseline (p < 0.05).
Likewise, there was no significant difference in pigment clearance between two
lasers either assessed by physician or patients. However, patients' satisfaction
score was significantly higher with the picosecond laser (p = 0.014). Adverse
events and pain were not different between groups. Q-switched KTP 532-nm
nanosecond laser and KTP 532-nm picosecond laser are safe and effective for
treating solar lentigines in Asians. Based on cost-effectiveness, Q-switched KTP
532-nm nanosecond laser remains the main treatment while KTP 532-nm picosecond
laser can be considered as a treatment option.
PMID- 29948458
TI - MicroRNAs in durum wheat seedlings under chronic and short-term nitrogen stress.
AB - Nitrogen is an essential macronutrient for plant growth and reproduction. In
durum wheat, an appropriate nitrogen soil availability is essential for an
optimal seed development. miRNAs contribute to the environmental change
adaptation of plants through the regulation of important genes involved in stress
processes. In this work, nitrogen stress response was evaluated in durum wheat
seedlings of Ciccio and Svevo cultivars. Eight small RNA libraries from leaves
and roots of chronically stressed plants were sequenced to detect conserved and
novel miRNAs. A total of 294 miRNAs were identified, 7 of which were described
here for the first time. The expression level of selected miRNAs and target genes
was analyzed by qPCR in seedlings subjected to chronic (Ciccio and Svevo, leaves
and roots) or short-term (Svevo roots) stress conditions. Some miRNAs showed an
immediate stress response, and their level of expression was either maintained or
returned to a basal level during a long-term stress. Other miRNAs showed a
gradual up- or downregulation during the short-term stress. The newly identified
miRNA ttu-novel-106 showed an immediate strongly downregulation after nitrogen
stress, which was negatively correlated with the expression of MYB-A, its
putative target gene. PHO2 gene was significantly upregulated after 24-48-h
stress, corresponding to a downregulation of miR399b. Ttu-miR399b putative
binding sites in the 5' UTR region of the Svevo PHO2 gene were identified in the
A and B genomes. Both MYB-A and PHO2 genes were validated for their cleavage site
using 5' RACE assay.
PMID- 29948459
TI - Comparative genomics analysis reveals gene family expansion and changes of
expression patterns associated with natural adaptations of flowering time and
secondary metabolism in yellow Camellia.
AB - Yellow-flowering species are unique in the genus Camellia not only for their
bright yellow pigments but also the health-improving substances in petals.
However, little is known regarding the biosynthesis pathways of pigments and
secondary metabolites. Here, we performed comparative genomics studies in two
yellow-flowered species of the genus Camellia with distinctive flowering periods.
We obtained 112,190 and 89,609 unigenes from Camellia nitidissima and Camellia
chuongtsoensis, respectively, and identified 9547 gene family clusters shared
with various plant species and 3414 single-copy gene families. Global gene
expression analysis revealed six comparisons of differentially expressed gene
sets in different developmental stages of floral bud. Through the identification
of orthologous pairs, conserved and specific differentially expressed genes
(DEGs) between species were compared. Functional enrichment analysis suggested
that the gibberellin (GA) biosynthesis pathway might be related to the alteration
of flowering responses. Furthermore, the expression patterns of secondary
metabolism pathway genes were analyzed between yellow- and red-flowered
Camellias. We showed that the key enzymes involved in glycosylation of flavonoids
displayed differential expression patterns, indicating that the direct
glycosylation of flavonols rather than anthocyanins was pivotal to coloration and
health-improving metabolites in the yellow Camellia petals. Finally, the gene
family analysis of UDP-glycosyltransferases revealed an expansion of group C
members in C. nitidissima. Through comparative genomics analysis, we demonstrate
that changes of gene expression and gene family members are critical to the
variation of natural traits. This work provides valuable insights into the
molecular regulation of trait adaptations of floral pigmentation and flowering
timing.
PMID- 29948461
TI - Absence of thyroid transcription factor-1 expression is associated with poor
survival in patients with advanced pulmonary adenocarcinoma treated with
pemetrexed-based chemotherapy.
AB - INTRODUCTION: Adenocarcinoma is the commonest histologic subtype of lung cancer
and is often identified by immunohistochemical staining for thyroid transcription
factor-1 (TTF-1). However, up to 20% of lung adenocarcinomas do not express TTF
1, and there is uncertainty regarding the significance of this. We aimed to
evaluate the prognostic effect of TTF-1 expression status on survival in patients
treated with pemetrexed-based chemotherapy for advanced adenocarcinoma of the
lung. METHODS: This retrospective study included patients treated with pemetrexed
based chemotherapy for stage IIIB/IV lung adenocarcinoma, who had known TTF-1
expression status. Clinical and demographic data were obtained from medical
records. Overall survival (OS) was estimated using the Kaplan-Meier method, and
differences in survival between groups assessed using the Cox proportional
hazards model. RESULTS: Forty-four patients were identified with documented TTF-1
expression: 35 with TTF-1-positive and 9 with TTF-1-negative disease. Patients in
the TTF-1-negative group had poorer performance scores than those in the TTF-1
positive group (ECOG 2: 67 vs 20%, p = 0.008), and received less chemotherapy
(median cycles 2 vs 4, p = 0.009), and were fewer in treatment with doublet
regimens (22 vs 69%, p = 0.013). OS was significantly shorter in the TTF-1
negative group than in the TTF-1-positive group (2.4 vs 11.5 months, HR 8.38, p <
0.0001). CONCLUSIONS: In this group of patients treated with pemetrexed-based
chemotherapy for advanced pulmonary adenocarcinoma, absence of TTF-1 expression
was associated with an aggressive tumor phenotype, poorer performance status, and
poor survival. This subgroup of patients should be recognized as having a
distinct clinical course, with limited benefit from standard chemotherapy.
PMID- 29948460
TI - Expansion and evolutionary patterns of GDSL-type esterases/lipases in Rosaceae
genomes.
AB - GDSL-type esterase/lipase (GELP) is mainly characterized by a conserved GDSL
domain at N terminus, and is widely found in all living species, both prokaryotes
and eukaryotes. GELP gene family consists of a wide range of members playing
important roles in plant physiological processes, such as development, stress
responses, and functional divergences. In our study, 597 GELP genes were
identified from six Rosaceae genomes (i.e., Fragaria vesca, Prunus persica,
Prunus avium, Prunus mume, Pyrus bretschneideri, and Malus domestica) by a
comprehensive analysis. All GELP genes were further divided into ten subfamilies
based on phylogenetic tree analysis. Subfamily D and subfamily E are the two
largest subfamilies. Microcollinearity analysis suggested that WGD/segmental
events contribute to the expansion of the GELP gene family in M. domestica and P.
bretschneideri compared to F. vesca, P. persica, P. avium, and P. mume. Some
PbGELPs were expressed during the fruit development of P. bretschneideri and
pollen tubes, indicating their activity in these tissues. The expression
divergence of PbGELP duplication gene pairs suggests that many mutations were
allowed during evolution, although the structure of GELP genes was highly
conserved. The current study results provided the feasibility to understand the
expansion and evolution patterns of GELP in Rosaceae genomes, and highlight the
function during P. bretschneideri fruits and pollen tubes development.
PMID- 29948462
TI - Neoadjuvant chemoradiation and breast reconstruction: the potential for improved
outcomes in the treatment of breast cancer.
AB - BACKGROUND: Immediate breast reconstruction (IBR) improves psychosocial and
quality of life outcomes. Post-mastectomy radiation therapy is indicated for
patients with a high risk of locoregional recurrence including locally advanced
tumours (>= 5 cm) or greater than or equal to four axillary nodes positive for
breast cancer and can be a relative contraindication to IBR. Administration of
radiation therapy pre-operatively, analogous to neoadjuvant chemotherapy, may
reduce time to completion of treatment and facilitate better access to IBR.
METHODS: This is a prospective pilot study in a tertiary referral breast cancer
unit, comparing surgical, pathological response and oncological outcomes and time
to completion of therapy for a prospective group of patients who received
neoadjuvant radiotherapy with a cohort of age- and stage-matched patients
requiring post-mastectomy (+/- reconstruction) radiation between 2010 and 2016.
RESULTS: Sixteen patients with locally advanced breast cancer underwent
neoadjuvant radiation and were age- and stage-matched to 32 patients who received
post-mastectomy radiation therapy (PMRT) between 2010 and 2016. Neoadjuvant
radiotherapy resulted in shorter time between diagnosis and treatment completion
(245.6 +/- 44.2 days in the neoadjuvant group, 291.2 +/- 36.7 days in the
adjuvant group, p = 0.001). A higher proportion of patients undergoing
neoadjuvant chemoradiation therapy underwent breast reconstruction (14/16
patients in the neoadjuvant group, 15/32 patients in the adjuvant group, p =
0.007) without an increase in complication rate (p = 0.117). There was a trend
towards improved pathological complete response and survival in the neoadjuvant
group. CONCLUSION: This pilot study confirms that neoadjuvant chemoradiation is a
feasible way of delivering breast cancer treatment and may facilitate improved
access to IBR.
PMID- 29948463
TI - Acute cerebellitis after administration of nivolumab and ipilimumab for small
cell lung cancer.
PMID- 29948464
TI - Topographical disorientation in aging. Familiarity with the environment does
matter.
AB - Topographical disorientation (TD) refers to navigational impairment as an effect
of aging or brain damage. Decreases in navigational performance with aging are
more due to deficits in the ability to mentally represent space in an object
centered (allocentric) than in a self-centered (egocentric) format.
Familiarity/remoteness of spatial memory traces can represent a protective factor
for TD in aging. Conversely, using newly learned information for assessment may
lead to overestimating TD severity as it combines two contributing factors:
heading (allocentric) disorientation and anterograde agnosia. A supplementary
evaluation of TD with aging according to ecological spatial tasks is recommended.
The core tasks should focus on landmark positioning, both on a blind map
(allocentric) and along a route (egocentric) of the hometown so as to disentangle
spatial memory for familiar/remote information from decline due to recent
encoding of information.
PMID- 29948465
TI - Dual infectious brainstem encephalitis with Aspergillus flavus and Haemophilus
influenza in an immunocompetent patient.
PMID- 29948466
TI - Ipilimumab treatment associated with myasthenic crises and unfavorable disease
course.
AB - Ipilimumab, a monoclonal antibody targeting the cytotoxic T lymphocyte antigen-4
is a treatment option for metastatic melanoma. This receptor serves as an
inhibitor receptor on T lymphocytes and blockage of these results predisposition
to autoimmune diseases. The patients with autoimmune disorders were excluded in
clinical trials and there is no sufficient data of the treatment on these
patients who already have an autoimmune disorder. Here, we report a case of
myasthenia gravis who was treated with ipilimumab and we presented the long-term
prognosis of the patient after treatment.
PMID- 29948467
TI - The imaging features of cerebral septic infarction in two patients with infective
endocarditis.
AB - BACKGROUND: Neurologic complications are frequently seen in infective
endocarditis (IE) and were identified in about 70% of patients with IE. However,
the imaging features of the cerebral septic infarction were less investigated.
PURPOSE: To demonstrate the imaging features of the cerebral septic infarction of
IE. MATERIAL AND METHODS: Two patients were clinically diagnosed as IE according
to the modified Duke criterion. We studied their imaging profiles and reviewed
the literature of the imaging features of neurologic complications of IE.
RESULTS: The critical features are multiple ischemic and hemorrhagic lesions,
most of which locate at the cortical-medullary junction. The septic infarctions
are irregular patchy in shape and have characteristic imaging features indicating
complications of IE. CONCLUSION: Magnetic resonance imaging (MRI) with different
sequences can detect the features and provide clinical evidence to physicians to
make the correct diagnoses and then the treatment plans.
PMID- 29948468
TI - Estimating dementia cases in the immigrant population living in Italy.
AB - INTRODUCTION: The phenomenon of dementia among immigrants and ethnic minorities
represents an emerging challenge for Western countries. The aim of the present
study was to estimate the number of dementia cases among immigrant subjects
residing in Italy and in each Italian region to provide pivotal information on
the magnitude of such public health issue. METHOD: The number of immigrant
individuals, aged 65 years or older, living in Italy and in the 20 Italian
regions was derived by the 2017 data of the National Institute for Statistics.
The dementia prevalence rates were taken from the European data provided by the
Neurologic Diseases in the Elderly Research Group. The estimated dementia cases
were calculated by multiplying the number of immigrants with the age- and sex
specific prevalence rates. RESULTS: Overall, 186,373 older immigrant subjects
lived in Italy in January 2017. Nearly 7700 dementia cases were estimated in this
population (5022 among women, 2725 among men). When considering each specific
Italian region, the number of estimated cases ranged from 19 (Basilicata) to 1500
(Lombardia) with a marked inter-regional variability. DISCUSSION: Our findings
indicate that the occurrence of dementia among immigrants and ethnic minorities
constitutes a novel but already relevant issue for our healthcare systems. A non
negligible number of immigrant individuals is probably already seeking or might
seek help for cognitive disturbances, thus potentially referring to general
practitioners and/or to the Italian dementia services. The forecasted increasing
magnitude of this phenomenon reinforces the need for tailored and locally
oriented initiatives and policies.
PMID- 29948470
TI - Perceived Role and Expectations of Health Care Providers in Return to Work.
AB - Purpose Health care providers (HCPs) play an important role in return to work
(RTW) and in the workers' compensation system. However, HCPs may feel unsure
about their responsibilities in the RTW process and experience difficulty making
recommendations about RTW readiness and limitations. This study examines the ways
in which HCPs and case managers (CMs) perceive HCPs role in the RTW process, and
how similarities and differences between these views, in turn, inform
expectations of HCPs. Methods In-depth interviews were conducted with 69 HCPs and
34 CMs from 4 provinces. Data were double coded and a thematic, inductive
analysis was carried out to develop key themes. Findings The main role of HCPs
was to diagnose injury and provide patients with appropriate treatment. In
addition, the majority of HCPs and CMs viewed providing medical information to
workers' compensation board (WCB) and the general encouragement of RTW as
important roles played by HCPs. There was less clarity, and at times
disagreement, about the scope of HCPs' role in providing medical information to
WCB and encouraging RTW, such as the type of information they should provide and
the timelines for RTW. Conclusion Interviews suggest that different role
expectations may stem from differing perspectives of HCPs and the CMs had
regarding RTW. A comprehensive discussion between WCB decision-makers and HCPs is
needed, with an end goal of reaching consensus regarding roles and
responsibilities in the RTW process. The findings highlight the importance of
establishing clearer role expectations.
PMID- 29948469
TI - A new tool to assess responsiveness in disorders of consciousness (DoC): a
preliminary study on the Brief Post-Coma Scale (BPCS).
AB - INTRODUCTION: The Brief Post-Coma Scale (BPCS) is an easy diagnostic tool for
individuals with disorders of consciousness (DoC), in a reduced version from a
previously Post-Coma Scale, that could distinguish patients in the minimally
conscious state (MCS) from those in unresponsive wakefulness syndrome (UWS),
formerly defined as vegetative state (VS). OBJECTIVE: Aim of the study was to
assess the diagnostic validity of the BPCS in comparison with the Coma Recovery
Scale-Revised (CRS-R), in its Italian validated version, the Disability Rating
Scale (DRS), the Level of Cognitive Functioning (LCF), and the Glasgow Outcome
Scale (GOS). METHODS: In an Italian multicenter study on 545 patients with DoC,
36 post-acute rehabilitation wards, 32 long-term care centers, and 2 family
associations participated to data collection. RESULTS: Statistically significant
correlations were found between the BPCS and the other clinical scales: R = 0.586
(p < 0.001) with LCF, R = - 0.566 (p < 0.001) with DRS, R = 0.622 (p < 0.001)
with CRS-R. The BPCS scores resulted significantly correlated with the time from
acute event (R = 0.117, p = 0.006). Patients with GOS score 2 had mean BPCS of
1.84 +/- 1.19, whereas those with GOS 3 had significantly higher scores 3.88 +/-
1.71 (p < 0.001). Similarly, in patients with vegetative state/UWS (VS/UWS), the
mean BPSC score was 1.71 +/- 1.09, significantly lower (p < 0.001) than that of
patients with minimally conscious state (BPCS = 3.83 +/- 1.29). Finally, the
agreement of the BPCS and clinical diagnosis was of 84.4%, with an odds ratio OR
= 3.781 (95% CI = 3.026-4.725, p < 0.001). CONCLUSIONS: The BPCS has demonstrated
statistically significant correlations with the most commonly used scales in
persons with DoC.
PMID- 29948471
TI - Interventions Developed with the Intervention Mapping Protocol in Work Disability
Prevention: A Systematic Review of the Literature.
AB - Purposes Intervention mapping (IM) is a protocol for developing effective
behavior change interventions. It has been used for 10 years to develop work
disability prevention (WDP) interventions, but it is not known to what extent and
with what success. The main objective of this study was to review the
effectiveness of these interventions. Secondary objectives were to review their
fidelity to the IM protocol, their theoretical frameworks and their content.
Methods A search strategy was conducted in MEDLINE, Web of Science, PsycINFO,
Pascal, Francis, and BDSP. All titles and abstracts were reviewed. A standardized
extraction form was developed. All included studies were reviewed by two
reviewers blinded to each other. Results Eight WDP interventions were identified
aimed at return to work (RTW; n = 6) and self-management at work (n = 2). RTW
interventions targeted workers with stress-related mental disorders (n = 1), low
back pain (n = 1), musculoskeletal disorders (n = 1), cancer (n = 2) and
gynecological surgery (n = 1). The fidelity to the IM protocol was weaker for the
participatory planning group. Matrices of change, change methods, and
applications were systematically reported. The main theoretical frameworks used
were the attitude-social influence-self efficacy model (n = 4) and the theory of
planned behavior (n = 2). Half of the interventions included a workplace
component (n = 4). Two interventions were reported as effective, and one
partially effective. Conclusion The IM protocol is used in WDP since 2007. The
participative dimension appears underused. Few theoretical frameworks were used.
Implications are to better consider the stakeholders involvement, and mobilize
theoretical frameworks with greater attempts to intervene on the work
environment.
PMID- 29948472
TI - Work Transitions in Breast Cancer Survivors and Effects on Quality of Life.
AB - Purpose Work transitions among breast cancer survivors remain an underexplored
area. We aimed to examine prevalence and determinants of changes in work status,
and the effect of these changes on quality of life of breast cancer survivors.
Methods A cross-sectional study of 410 female breast cancer survivors randomly
drawn from a larger study sample pool (n = 2644), members of "Leumit" healthcare
fund, who were diagnosed with primary nonmetastatic invasive breast cancer in the
years 2002-2012. The study questionnaire included questions on work
characteristics and health-related quality-of-life and was completed by all women
contacted. Work transition was defined as a downgrade (from full-time to part
time), termination, or retirement, and was contrasted to no change in work status
(retention of full-time or part-time). Work transition was assessed at two
intervals: between breast cancer diagnosis and treatment, and between breast
cancer diagnosis and time of the survey. Results A total of 206 breast cancer
survivors (50%) were employed prior to their diagnosis, of whom 12% stopped
working, and 79% downgraded to part-time during treatment. At the time of survey
(mean 8 +/- 3 years post-diagnosis), 33% of those employed prior to their
diagnosis stopped working or retired, 48% downgraded to part-time, and 19% had no
change in their work situation. Work transition between diagnosis and time of the
survey was significantly associated with poorer quality-of-life. In multivariable
analyses, work transition between diagnosis and time of the survey was positively
associated with being immigrant compared to native-born Israeli (odds ratio (OR)
4.65; 95% confidence interval (CI) 1.91-11.37; P = .001), and inversely with
education level of college or over compared to high school or less (OR 0.27; 95%
CI 0.09-0.86; P = .026). Conclusions Breast cancer survivors with characteristics
pointing at underprivileged social circumstances more often experienced changes
in work status after surviving breast cancer, irrespective of diagnosis,
comorbidity or treatment. Breast cancer patients with immigrant status and/or
lower educational attainment need more support to be able to keep their job.
PMID- 29948473
TI - Early Identification of Potential SSDI Entrants in California: The Predictive
Value of State Disability Insurance and Workers' Compensation Claims.
AB - Purpose Examine the potential for using information in short-term disability
claims to identify workers at high risk of leaving the workforce and entering
Social Security Disability Insurance (SSDI). Methods We analyze state-wide
California data on claimants of State Disability Insurance (SDI) and Workers'
Compensation (WC) and present statistics on: (1) characteristics (primary
diagnosis, sex, age, geography, wage level) by claim duration (0-3, 4-6, 7-12, 12
+ months); and (2) the ability of initial claim characteristics to predict
duration of at least 12 months. All data are for claims with disability lasting
more than 1 week. Results 22.2% of SDI claims last longer than 6 months and 12.5%
last 12 months. More WC claims reach these durations: 33.7 and 18.6%,
respectively. Long-term SDI and WC claimants are similar to SSDI awardees,
nationwide, but differ in age distribution; they are typically younger.
Conclusions Characteristics of SDI and WC claims can help predict claims likely
to last 12 months, but more information is needed to effectively target early
intervention services. Waiting longer to intervene improves targeting but risks
missing opportunities where early intervention could be more effective.
Collecting additional information at SDI or WC entry or soon thereafter could
improve both the efficiency and timing of interventions.
PMID- 29948474
TI - Three-step procedure for safe internal jugular vein catheterization under
ultrasound guidance.
AB - Real-time ultrasound guidance for central venous catheterization has become a
standard technique. This technique has been reported to yield high success rates
and fewer complications compared with landmark techniques. However, it can be
risky when the practitioner does not possess proper knowledge and skills. Lose
sight of the needle tip can lead to severe complications such as arterial
puncture or pneumothorax. Also, posterior wall penetration of the target vessels
must be avoided. Misplacement of the catheter to other vessels can sometimes
occur, and may only be discovered after the catheterization procedure. To avoid
these complications, we perform a three-step procedure to place an internal
jugular vein catheter under ultrasound guidance. The three steps are: (a) advance
the needle tip to the internal jugular vein with a short-axis image with an out
of-plane technique, (b) rupture the anterior wall by using a long-axis image with
an in-plane technique, and (c) confirm the guidewire position from the internal
jugular vein to the brachiocephalic vein using a short-axis image, and a coronal
image from the supraclavicular fossa. For safe needle advancement and penetration
of the anterior wall of the vein, combined use of short-axis and long-axis images
is helpful, and guidewire placement should be confirmed by scanning with the
short-axis image and the coronal image.
PMID- 29948475
TI - Correlation between acoustic radiation force impulse (ARFI)-based tissue
elasticity measurements and perfusion parameters acquired by perfusion CT in
cirrhotic livers: a proof of principle.
AB - PURPOSE: To investigate whether liver stiffness measured by acoustic radiation
force impulse (ARFI) sonoelastography always correlates with the liver perfusion
parameters quantified by perfusion CT in patients with known liver cirrhosis.
METHODS: Sonoelastography and perfusion CT were performed in 50 patients (mean
age 65.5; range 45-87 years) with liver cirrhosis, who were classified according
to Child-Pugh into class A (30/50, 60%), B (17/50, 34%), and C (3/50, 6%). For
standardized ARFI measurements in the left liver lobe at a depth of 4 cm, a
convex 6-MHz probe was used. CT examinations were performed using 80 kV, 100 mAs,
and 50 ml of iodinated contrast agent injected at 5 ml/s. Using standardized
region-of-interest measurements, we quantified arterial, portal venous, and total
liver perfusion. RESULTS: There was a significant linear correlation between
tissue stiffness and arterial liver perfusion (p = 0.015), and also when limiting
the analysis to patients with histology (p = 0.019). In addition, there was a
positive correlation between the total blood supply (arterial + portal-venous
liver perfusion) to the liver and tissue stiffness (p = 0.001; with histology, p
= 0.027). Shear wave velocity increased with higher Child-Pugh stages (p =
0.013). CONCLUSION: The degree of tissue stiffness in cirrhotic livers correlates
expectedly-even if only moderately-with the magnitude of arterial liver perfusion
and total liver perfusion. As such, liver elastography remains the leading
imaging tool in assessing liver fibrosis.
PMID- 29948476
TI - Changes in cardiac contractility during graded exercise are greater in subjects
with smaller body mass index, and greater in men than women: analyses using wave
intensity and force-frequency relations.
AB - INTRODUCTION AND PURPOSE: Estimation of the contractility of the left ventricle
during exercise is an important part of the rehabilitation protocol. It is known
that cardiac contractility increases with an increase in heart rate. This
phenomenon is called the force-frequency relation (FFR). Using wave intensity, we
aimed to evaluate FFR noninvasively during graded exercise. METHODS: We enrolled
83 healthy subjects. Using ultrasonic diagnostic equipment, we measured wave
intensity (WD), which was defined in terms of blood velocity and arterial
diameter, in the carotid artery and heart rate (HR) before and during bicycle
ergometer exercise. FFRs were constructed by plotting the maximum value of WD
(WD1) against HR. We analyzed the variation among FFR responses of individual
subjects. RESULTS: WD1 increased linearly with an increase in HR during exercise.
The average slope of the FFR was 1.0 +/- 0.5 m/s3 bpm. The slope of FFR decreased
with an increase in body mass index (BMI). The slopes of FFRs were steeper in men
than women, although there were no differences in BMI between men and women.
CONCLUSIONS: The FFR was obtained noninvasively by carotid arterial wave
intensity (WD1) and graded exercise. The slope of the FFR decreased with an
increase in BMI, and was steeper in men than women.
PMID- 29948477
TI - Comprehensive Registry of Esophageal Cancer in Japan, 2011.
PMID- 29948478
TI - Correction to: Comprehensive Registry of Esophageal Cancer in Japan, 2011.
AB - In the original publication of the article, the below name of institutions were
not included in the table of Institution-registered cases in 2011.
PMID- 29948479
TI - Histological study of the thin membranous structure made of dense connective
tissue around the esophagus in the upper mediastinum.
AB - BACKGROUND: The structure of the fascia in upper mediastinum has already been
reported from gross anatomical viewpoints by Sarrazin. But it is necessary to
understand meticulous anatomy for thoracoscopic or mediastinoscopic surgery. So
herein, we investigate histologically the thin membranous structure made of dense
connective tissues. METHODS: Semi-sequential transverse sections of the
mediastinum were obtained from three cadavers. Hematoxylin and eosin staining,
Elastica van Gieson staining, and Masson trichrome staining were performed to
identify the presence and location of the thin membranous structure made of dense
connective tissues. RESULTS: The "visceral sheath" and "vascular sheath," as
previously described by Sarrazin, were observed histologically. These two thin
membranous structures do not surround the esophagus and trachea cylindrically. In
addition, the "visceral sheath" on the right side of the upper mediastinum was
unclear in comparison to the left side. The "visceral sheath" (on the left side)
gradually became unclear, and seemed to almost disappear; the esophagus was found
to be very close to the thoracic duct on the caudal side of the bifurcation of
the trachea. Although the left recurrent nerve was located inside the "visceral
sheath" in all cadavers, the left recurrent nerve lymph nodes were located inside
the "visceral sheath" in cadaver 1 and between the "visceral sheath" and
"vascular sheath" in cadaver 3. CONCLUSION: The "visceral sheath" around the
esophagus in the upper mediastinum was histologically demonstrated; however, the
findings were not constant.
PMID- 29948480
TI - Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF
R) for advanced cervical esophageal cancer.
AB - BACKGROUND: Recently, definitive chemoradiotherapy (dCRT) has become one of the
essential treatment strategies for esophageal squamous cell carcinoma (ESCC) and
has been especially gaining prevalence for cervical ESCC to preserve the larynx.
Our department recently introduced dCRT concomitant with docetaxel, cisplatin,
and 5-fluorouracil (DCF-R) for treating advanced cervical ESCC. This study aims
to assess the safety and outcomes of DCF-R in patients with advanced cervical
ESCC. METHODS: We retrospectively assessed 11 patients with advanced cervical
ESCC (clinical stage: II-IV, including T4b and/or M1 lymph node) who received DCF
R as the first-line treatment between December 2010 and February 2015. RESULTS:
Our patient cohort comprised 8 males and 3 females (median age 68 years; range 54
76 years). The pretreatment clinical stage included stage II (1), stage III (7),
and stage IV (3) cases [including 3 patients with T4b (2 trachea and 1 thyroid)
and 3 patients with M1 lymph node]. We attained complete response (CR) in 10
patients and stable disease in 1 patient. Of 10 patients with CR, 5 experienced
recurrence and 5 continued exhibiting CR. Furthermore, grade 3 or more adverse
events included leucopenia (91%), neutropenia (91%), febrile neutropenia (45%),
and pharyngeal pain (55%). While the 2-year overall survival rate was 72%, the 2
year recurrent-free survival rate was 64%, respectively. CONCLUSIONS: DCF-R
treatment for advanced cervical esophageal cancer could be completed by the
careful administration; although a strong blood toxicity might occur, this
treatment may provide the chance to obtain favorable prognosis with larynx
preservation.
PMID- 29948481
TI - Oxygen in mitochondrial disease: can there be too much of a good thing?
PMID- 29948482
TI - Postsynaptic movement disorders: clinical phenotypes, genotypes, and disease
mechanisms.
AB - Movement disorders comprise a group of heterogeneous diseases with often complex
clinical phenotypes. Overlapping symptoms and a lack of diagnostic biomarkers may
hamper making a definitive diagnosis. Next-generation sequencing techniques have
substantially contributed to unraveling genetic etiologies underlying movement
disorders and thereby improved diagnoses. Defects in dopaminergic signaling in
postsynaptic striatal medium spiny neurons are emerging as a pathogenic mechanism
in a number of newly identified hyperkinetic movement disorders. Several of the
causative genes encode components of the cAMP pathway, a critical postsynaptic
signaling pathway in medium spiny neurons. Here, we review the clinical
presentation, genetic findings, and disease mechanisms that characterize these
genetic postsynaptic movement disorders.
PMID- 29948483
TI - A novel and effective inhibitor combination involving bortezomib and OTSSP167 for
breast cancer cells in light of label-free proteomic analysis.
AB - PURPOSE: The 26S proteasome plays important roles in many intracellular processes
and is therefore a critical intracellular cellular target for anticancer
treatments. The primary aim of the current study was to identify critical
proteins that may play roles in opposing the antisurvival effect of the
proteasome inhibitor bortezomib together with the calcium-chelator BAPTA-AM in
cancer cells using label-free LC-MS/MS. In addition, based on the results of the
proteomic technique, a novel and more effective inhibitor combination involving
bortezomib as well as OTSSP167 was developed for breast cancer cells. METHODS AND
RESULTS: Using label-free LC-MS/MS, it was found that expressions of 1266
proteins were significantly changed between the experimental groups. Among these
proteins were cell division cycle 5-like (Cdc5L) and drebrin-like (DBNL). We then
hypothesized that inhibition of the activities of these two proteins may lead to
more effective anticancer inhibitor combinations in the presence of proteasomal
inhibition. In fact, as presented in the current study, Cdc5L phosphorylation
inhibitor CVT-313 and DBNL phosphorylation inhibitor OTSSP167 were highly
cytotoxic in 4T1 breast cancer cells and their IC50 values were 20.1 and 43 nM,
respectively. Under the same experimental conditions, the IC50 value of BAPTA-AM
was found 19.9 MUM. Using WST 1 cytotoxicity assay, it was determined that 10 nM
bortezomib + 10 nM CVT-313 was more effective than the control, the single
treatments, or than 5 nM bortezomib + 5 nM CVT-313. Similarly, 10 nM bortezomib +
10 nM OTSSP167 was more cytotoxic than the control, the monotherapies, 5 nM
bortezomib + 5 nM OTSSP167, or than 5 nM bortezomib + 10 nM OTSSP167, indicating
that bortezomib + OTSSP167 was also more effective than bortezomib + CVT-313 in a
dose-dependent manner. Furthermore, the 3D spheroid model proved that bortezomib
+ OTSSP167 was more effective than the monotherapies as well as bortezomib + CVT
313 and bortezomib + BAPTA-AM combinations. Finally, the effect of bortezomib +
OTSSP167 combination was tested on MDA-MB-231 breast cancer cells, and it
similarly determined that 20 nM bortezomib +40 nM OTSSP167 combination completely
blocked the formation of 3D spheroids. CONCLUSIONS: Altogether, the results
presented here indicate that bortezomib + OTSSP167 is a novel and effective
combination and may be tested further for cancer treatment in vivo and in
clinical settings.
PMID- 29948484
TI - Identification of a new mating group and reproductive isolation in the Closterium
peracerosum-strigosum-littorale complex.
AB - Reproductive isolation is essential for the process of speciation. In order to
understand speciation, it is necessary to compare one mating group with other
phylogenetically related but reproductively isolated groups. The Closterium
peracerosum-strigosum-littorale (C. psl.) complex is a unicellular isogamous
zygnematophycean alga, which is believed to share a close phylogenetic
relationship with the land plants. In this study, we identified a new mating
group, named group G, of C. psl. complex and compared its physiological and
biochemical characteristics with the mating group I-E, which was closely related
to the mating group G. Zygospores are typically formed as a result of conjugation
between mating-type plus (mt+) and mating-type minus (mt-) cells in the same
mating group during sexual reproduction. Crossing experiments revealed mating
groups G and I-E were reproductively isolated from each other, but the release of
lone protoplasts from mt- cells of mating group G was induced in the presence of
mt+ cells of mating group I-E. In fact, the sex pheromone, protoplast-release
inducing protein of mating group I-E induced the release of protoplasts from mt-
cells of mating group G. When mt+ and mt- cells of both mating groups I-E and G
were co-cultured (multiple-choice matings), the zygospore formation of mating
group G, but not that of mating group I-E, was inhibited. Based on these results,
we propose a possible mechanism of reproductive isolation between the two mating
groups and suggest the presence of sexual interference between mating group G and
mating group I-E.
PMID- 29948485
TI - Polyphyletic origin in Pimpinella (Apiaceae): evidence in Western Europe.
AB - The genus Pimpinella L. comprises about 150 species, being one of the largest
genera within the family Apiaceae (subfamily Apioideae). Previous molecular
phylogenetic studies have shown that Pimpinella is a taxonomically complex group.
In this study, evolutionary relationships among representatives from Western
Europe have been inferred from phylogenetic analyses of nuclear ribosomal DNA
internal transcribed spacer (ITS 1 and ITS 2) and plastid sequences (trnL intron
and the trnL-F spacer), with a representative sampling included (168 accessions
in the ITS analysis, representing 158 species; and 42 accessions in the cpDNA
analysis representing 35 taxa of Pimpinella and closely related species). All
analyses resolved that Pimpinella is a non-monophyletic group, and Pimpinella's
taxa that grow in Western Europe are part of phylogenetically independent groups
that correspond to three different tribes of the subfamily Apioideae:
Pimpinelleae (core group), Pyramidoptereae and Smyrnieae.
PMID- 29948486
TI - Low assimilation efficiency of photorespiratory ammonia in conifer leaves.
AB - Glutamine synthetase (GS) localized in the chloroplasts, GS2, is a key enzyme in
the assimilation of ammonia (NH3) produced from the photorespiration pathway in
angiosperms, but it is absent from some coniferous species belonging to Pinaceae
such as Pinus. We examined whether the absence of GS2 is common in conifers
(Pinidae) and also addressed the question of whether assimilation efficiency of
photorespiratory NH3 differs between conifers that may potentially lack GS2 and
angiosperms. Search of the expressed sequence tag database of Cryptomeria
japonica, a conifer in Cupressaceae, and immunoblotting analyses of leaf GS
proteins of 13 species from all family members in Pinidae revealed that all
tested conifers exhibited only GS1 isoforms. We compared leaf NH3 compensation
point (gammaNH3) and the increments in leaf ammonium content per unit
photorespiratory activity (NH3 leakiness), i.e. inverse measures of the
assimilation efficiency, between conifers (C. japonica and Pinus densiflora) and
angiosperms (Phaseolus vulgaris and two Populus species). Both gammaNH3 and NH3
leakiness were higher in the two conifers than in the three angiosperms tested.
Thus, we concluded that the absence of GS2 is common in conifers, and
assimilation efficiency of photorespiratory NH3 is intrinsically lower in conifer
leaves than in angiosperm leaves. These results imply that acquisition of GS2 in
land plants is an adaptive mechanism for efficient NH3 assimilation under
photorespiratory environments.
PMID- 29948487
TI - Comparison of aboveground vegetation and soil seed bank composition at sites of
different grazing intensity around a savanna-woodland watering point in West
Africa.
AB - Grazing removes a plant's aboveground vegetative and reproductive tissues and can
modify the soil seed bank, potentially impacting the restoration of preferred
species. Knowledge about aboveground vegetation and species composition of soil
seed bank and the processes that contribute to vegetation recovery on and
surrounding watering points subjected to grazing is lacking. Successful
restoration strategies hinge on addressing these knowledge gaps. We assessed the
effects of livestock grazing on aboveground vegetation and soil seed bank
characteristics along a river bank and surrounding areas subject to different
grazing intensities and draw implications for restoration. Plots (50 * 50 m) were
established along five transects representing differing levels of grazing
intensity. Soil samples were taken from three layers within each plot to
determine soil properties and species composition of soil seed bank using the
seedling emergence method. Heavy grazing resulted in the disappearance of
perennial grasses, a reduction in species diversity and a decrease in soil
nutrients with increased soil depth. Overall, the similarity between the extant
aboveground vegetation and flora within the soil seed bank was low. The soil seed
bank was dominated by herbaceous species and two woody species, suggesting that
many woody species are not accumulating in the soil. With increasing soil depth,
the seed density and richness declined. Canonical correspondence analyses (CCAs)
showed that emerged seedlings from the soil seed bank were significantly
influenced by soil carbon, organic matter, total nitrogen, total potassium and
soil cation exchange capacity. This finding suggests that current grazing
practices have a negative impact on the vegetation surrounding watering points;
hence there is a need for improved grazing management strategies and vegetation
restoration in these areas. The soil seed bank alone cannot restore degraded
river banks; active transfer of propagules from adjacent undisturbed forest areas
is essential.
PMID- 29948488
TI - The cellular machineries responsible for the division of endosymbiotic
organelles.
AB - Chloroplasts (plastids) and mitochondria evolved from endosymbiotic bacteria.
These organelles perform vital functions in photosynthetic eukaryotes, such as
harvesting and converting energy for use in biological processes. Consistent with
their evolutionary origins, plastids and mitochondria proliferate by the binary
fission of pre-existing organelles. Here, I review the structures and functions
of the supramolecular machineries driving plastid and mitochondrial division,
which were discovered and first studied in the primitive red alga Cyanidioschyzon
merolae. In the past decade, intact division machineries have been isolated from
plastids and mitochondria and examined to investigate their underlying structure
and molecular mechanisms. A series of studies has elucidated how these division
machineries assemble and transform during the fission of these organelles, and
which of the component proteins generate the motive force for their contraction.
Plastid- and mitochondrial-division machineries have important similarities in
their structures and mechanisms despite sharing no component proteins, implying
that these division machineries evolved in parallel. The establishment of these
division machineries might have enabled the host eukaryotic ancestor to
permanently retain these endosymbiotic organelles by regulating their binary
fission and the equal distribution of resources to daughter cells. These findings
provide key insights into the establishment of endosymbiotic organelles and have
opened new avenues of research into their evolution and mechanisms of
proliferation.
PMID- 29948489
TI - Impact of dexmedetomidine on the tissue distribution, anesthetic action, and
hemodynamic effects of mepivacaine.
AB - The present study investigated the regional blood flow, tissue distribution,
local anesthetic action, and hemodynamic effects of mepivacaine containing
dexmedetomidine hydrochloride (DEX) in rats. Blood flow was measured after
injection of 0.5% mepivacaine (M group), 12.5 ug/ml DEX (D group), or 0.5%
mepivacaine containing 12.5 ug/ml DEX (DM group) into the upper lip. Mepivacaine
distribution was autoradiographically observed in maxillary bone resected after
injection of 0.5% 3H-mepivacaine (HM group) or 0.5% 3H-mepivacaine containing
12.5 ug/ml DEX (DHM group) into the palatal mucosa adjacent to the right
maxillary first molar. Radioactivity was also measured using a liquid
scintillation counter. SEP were measured to analyze anesthetic action. Blood
pressure and heart rate were measured to compare hemodynamic effect. The addition
of DEX significantly decreased blood flow compared to M group from 10 to 60 min
after injection. The addition of DEX significantly increased the amount of
radioactivity compared to HM group in the palatal mucosa from 5 to 60 min after
injection and in the body of the maxilla from 2 to 60 min after injection.
Maximum blood radioactivity was measured at 5 min after injection in HM group and
50 min after injection in DHM group. The addition of DEX significantly decreased
peak-to-peak amplitudes compared to M group until 60 min after injection. No
significant hemodynamic differences were observed. DEX enhances the action of
mepivacaine in reducing regional blood flow prolongs its tissue retention, and
increases the local anesthetic action without affecting hemodynamics on local
administration.
PMID- 29948490
TI - Effects of crown movement on periodontal biotype: a digital analysis.
AB - Orthodontic treatment has important correlations with periodontal changes.
Various mechanical and biological factors are involved in determining such
changes, but anatomical and morphological variables, generally addressed as
periodontal biotype, play a key role. In measurement of such modifications,
digital and non-contact reverse engineering technologies may be of tremendous
advantage. The aim of this study is to retrospectively evaluate, in a series of
digitized dental casts, some of the parameters addressing periodontal biotype and
correlate them to extent and direction of tooth movement. Pre- (T0) and post
treatment (T1) dental casts of 22 patients were scanned by 3Shape TRIOS 3(r)
scanner. A number of variables (crown ratio, gingival margin position, gingival
contour, papillae position, gingival scallop) were investigated and their
variations calculated after digital measurements on single casts at T0 and T1, or
after direct measurement (T1 vs T0) on the superimposition and alignment of
digital models. Univariate and multivariate statistics were then performed. No
significant correlation was detected between the sagittal or vertical movement of
dental crown and displacement of the gingival margin. On the other hand,
vestibular gingival contour resulted significantly altered by vestibular and
extrusion movements. Further studies are needed to ascertain the differential
effect of bone and soft tissue on such modifications. The relationship between
orthodontic treatment and the periodontium overcomes the consideration of
gingival recession and includes all the concepts of periodontal biotype with its
characteristics. Digital technologies and non-contact reverse engineering
techniques now available have the potential to allow a more precise definition of
such a relationship.
PMID- 29948491
TI - Polymerization shrinkage and shrinkage force kinetics of high- and low-viscosity
dimethacrylate- and ormocer-based bulk-fill resin composites.
AB - The aim of the present study was to investigate polymerization shrinkage,
shrinkage force development, and degree of monomer conversion of high- and low
viscosity dimethacrylate- and ormocer-based bulk-fill resin composites. Two
flowable bulk-fill composites (SDR, x-tra base), two high-viscosity bulk-fill
composites (Bulk Ormocer, SonicFill), and two conventional composite materials
(Esthet X flow, Esthet X HD) were photoactivated for 20 s at 1275 mW/cm2. Linear
polymerization shrinkage and shrinkage force were recorded in real time using
custom-made devices, and the force rate and time to achieve maximum force rate
were determined. Degree of conversion was measured using Fourier-transform
infrared spectroscopy. Data were analyzed with one-way ANOVA and Tukey's HSD post
hoc test, and bivariate correlations were computed (alpha = 0.05). The category
of high-viscosity bulk-fill resin composites showed the significantly lowest
polymerization shrinkage and force development. Within the tested flowable
composite materials, SDR bulk-fill generated the significantly lowest shrinkage
forces during polymerization and attained the significantly highest degree of
conversion. Strong positive correlations were revealed between shrinkage force
and both linear polymerization shrinkage (r = 0.902) and maximum force rate (r =
0.701). Linear shrinkage and shrinkage force both showed a negative correlation
with filler volume content (r = - 0.832 and r = - 0.704, respectively). Bulk-fill
resin composites develop lower shrinkage forces than their conventional flowable
and high-viscosity counterparts, respectively, which supports their use for
restoring high C-factor posterior cavities. Overall, bulk-fill composites with
high filler amount and low force rate showed the most favorable shrinkage force
characteristics.
PMID- 29948492
TI - Neuropsychiatric clinical manifestations in elderly patients treated with
hydroxychloroquine: a review article.
AB - Little is known about the development of psychosis during hydroxychloroquine
(HCQ) treatment, especially in elderly patients affected by rheumatic diseases,
with multiple comorbidities and treatments. To summarize the available evidence
on HCQ-induced psychosis in elders, we performed a literature review.
Additionally, individual case safety reports sent to the European
Pharmacovigilance database (EudraVigilance) with HCQ as suspected drug and
related to adverse events belonging to the System Organ Class 'Psychiatric
disorders' were shown. Over the years, evidence was published about the risk of
neuropsychiatric clinical manifestations during HCQ treatment for rheumatic
diseases, but few of them were related to elderly patients. These adverse events
can include less severe clinical manifestations such as affect lability and
nervousness or more severe conditions such as actual psychosis and suicidal
tendencies, which frequency are actually unknown. The presence of risk factors in
these patients may precipitate HCQ-induced psychosis and their precocious
detection could be associated with a risk minimization. Among predisposing risk
factors, there are the co-exposure to interacting drugs, alcohol intake, familial
history of psychiatric diseases, female gender, and the concomitant use of low
dose glucocorticoids. In some cases it was possible to reverse psychotic
behaviour with the antipsychotic treatment or with HCQ suspension.
PMID- 29948493
TI - Effect of Synadenium grantii and its isolated compound on dysmenorrhea behavior
model in mice.
AB - OBJECTIVE: This study aimed to evaluate the effects of the methanol extract of
Synadenium grantii Hook f. stems and its main isolated compound Query3,4,12,13
tetraacetylforbol-20-phenylacetate (1) on experimental dysmenorrhea in mice.
METHODS: Female Swiss mice (n = 6-15) of 6-8 weeks old were used, selected
according to the period of the estrous cycle. Animals in proestrus were treated
intraperitoneally (i.p.) for 3 days with estradiol. They orally received, on the
4th day, S. grantii extract, the compound 1, ibuprofen or hyoscine butylbromide
(Buscopan compound(r)). Then they were injected (i.p.) with oxytocin 1 h later
and individually observed regarding the abdominal writhing for 45 min. The uterus
was weighed, photographed and fixed in paraffin for histological analysis. KEY
FINDINGS: The extract inhibited the abdominal writhing and similar results were
obtained with compound 1 and the positive control drugs Ibuprofen and hyoscine
butylbromide. Reduction of uterus volume and histological inflammatory
parameters, such as oedema and leukocyte infiltrate, were observed in animals
treated with the extract and compound 1. CONCLUSIONS: Our data show promising
activity of the extract against dysmenorrhea, indicating important anti
inflammatory activity. Compound 1 appears to be, at least in part, the main
responsible for this promising biological effect.
PMID- 29948494
TI - Anti-inflammatory and anti-arthritic effects of methanol extract of the stem bark
of Boswellia dalzielii Hutch (Burseraceae) in rats.
AB - Boswellia dalzielii is a tall tree (more than 13 m high) that produces aromatic
white flowers. This plant is commonly used in indigenous medicine across Africa
against diarrhea, malaria, vomiting, inflammation and arthritis. The present
study focuses on the anti-inflammatory and anti-arthritis potential of methanol
extract of Boswellia dalzielii (BDME). Anti-inflammatory activity was evaluated
in inflammatory models induced by carrageenan, arachidonic acid, histamine,
serotonin, prostaglandin and bradykinin. Anti-arthritis activity was measured
using complete Freund's adjuvant model. Intracellular and extracellular ROS
production and proliferation of T-cells were evaluated using chemiluminescence
and liquid scintillation counter techniques, respectively. TNF-alpha and IL-1beta
production were assessed using ELISA and MTT assay performed for cytotoxicity.
BDME revealed a significant anti-inflammatory effect by preventing the
development of edema caused by carrageenan, arachidonic acid, histamine,
serotonin, prostaglandin and bradykinin. For anti-arthritic properties of BDME,
the results showed a significant reduction of the joint diameter and a decrease
in pain in the treated animals. The extract also showed a noticeable systemic
effect, maintaining the values of the evaluated parameters close to normal in
treated rats with an inhibition of joint destruction as shown in
histopathological analysis. Furthermore, BDME exhibited significant inhibition of
extracellular and intracellular ROS production. Still, the extract displayed
significant inhibitory activity on T-cell proliferation as well as a reduced
production of TNF-alpha and IL-1beta. Boswellia dalzielii could be considered as
a promising tract in the prevention and/or management of inflammatory diseases.
PMID- 29948495
TI - Rate and risk factors for a hyperactivity delirium in patients with aneurysmal
subarachnoid haemorrhage.
AB - Hyperactive delirium (agitation) is a common complication in patients on
intensive care units and can be assessed by the Richmond Agitation and Sedation
Scale (RASS) in principle. However, the role of agitation in patients with
aneurysmal subarachnoid haemorrhage (SAH) is poorly understood. We performed a
retrospective analysis to identify risk factors for the development of a
hyperactive delirium and its functional consequences for neurological outcome.
Three hundred thirty-eight patients with SAH were screened in this study
resulting in 212 patients which reached at least once a RASS of 0 and were
eligible for further analysis. Clinical characteristics were analysed towards the
occurrence of a hyperactive delirium. Neurological outcome at discharge and
follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212
patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to
11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR)
3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping
(OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p
= 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be
significantly associated with the development of agitation. Medical history of
psychiatric disorders, alcohol or nicotine abuse showed no correlation with
agitation. Cox regression analysis revealed no significant influence of agitation
towards unfavourable outcome at discharge or follow-up. We provide four
independent risk factors for the development of agitation in SAH patients. Our
study emphasizes the specific entity of agitation in patients with SAH and
underscores its relevance in neurological patients.
PMID- 29948496
TI - Evaluation of the risk of rupture of intracranial aneurysms in patients with
aneurysmal subarachnoid hemorrhage according to the PHASES score.
AB - The PHASES score was developed to determine the risk of rupture of un-ruptured
intracranial aneurysms (UIAs). The purposes of the current study were to apply
this score on patients with actually ruptured intracranial aneurysms and to
analyze the hypothetically prediction of the risk in this particularly patient
group. We extracted the data of 100 recently treated patients (23 male, 77
female, mean age 56.4 years, range 17-93 years) with ruptured saccular
intracranial aneurysms from our prospectively maintained neurovascular database
according to the parameters used in the PHASES score (population, hypertension,
age, earlier SAH, size and site of the aneurysm). Descriptive statistical
analysis was performed using SPSS for Windows version 18.0 (SPSS Inc., Chicago,
Illinois, USA). Ninety-nine percent of the patients were European and 1% Japanese
in our series. Pre-existing arterial hypertension was found in 59%. Fifteen
percent of the patients were > 75 years. Earlier SAH was found in 1%. The site of
the aneurysms were the internal carotid artery (ICA) in 10%, the middle cerebral
artery (MCA) in 14%, and arteries of the anterior and posterior circulation (PC)
including the posterior communicating artery (PCOM) in 76%. Sixty-six percent of
the aneurysms were smaller than 7 mm, 18% ranged between 7 and 9.9 mm, 14% were
between 10 and 19.9 mm, and 2% were larger than 20 mm. European population,
aneurysm size < 7 mm, and age < 75 years scored with 0 point in the PHASES study
occurred most frequently in our series. The distribution of the aneurysm site to
the anterior and posterior circulation scored with 4 points occurred most
frequently. Considering the 5-year risk of rupture, 70% of our patient collective
would have an estimated risk of < 2%. Interestingly, 70% of the patients with
aneurysmal SAH had a low risk profile and would have a low risk of rupture
according to the PHASES score in our series. This observation underlines the
discrepancy of the estimated low risk of rupture for UIAs in young and healthy
patients and the obvious fact the majority of the SAH patients are actually young
with low risk factors. Parameters beyond the features of the PHASES score are
needed to determine the risk of rupture of intracranial aneurysms.
PMID- 29948497
TI - The correlation between gene polymorphisms of endothelial nitric oxide synthase
and aneurismal subarachnoid hemorrhage.
AB - To discuss the association of the T786C and G894T polymorphisms of endothelial
nitric oxide synthase (eNOS) with the occurrence and prognosis of aneurismal
subarachnoid hemorrhage (aSAH). One hundred sixty-nine patients with aSAH were
collected as the case group, which was divided into the good prognosis group and
adverse prognosis group according to the condition 3 months after the treatment.
One hundred fifty-six healthy volunteers were collected as the control group. The
allele and genotype of T786C and G894T polymorphisms of eNOS were detected by
polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
The genotype and allele frequency of eNOS were compared between different groups.
And then, the risk factors of aSAH occurrence and prognosis were analyzed by
using the logistic regression model. Both the genotype and allele frequency
distributions of T786C and G894T between the case group and control group were
significantly different (P < 0.05). There were significant differences in the
distribution of G894T and T786C allele frequency and G894T genotype between the
good prognosis group and adverse prognosis group, and there was no difference in
T786C genotype. The results of the logistic regression analysis indicated that
T786C and G894T polymorphisms of eNOS were independent influencing factors on the
occurrence of aSAH and the G894T polymorphism was also closely related to the
prognosis. T786C and G894T polymorphisms of eNOS gene were correlated with the
occurrence and prognosis of aSAH, and the G894T polymorphism might be an
independent influencing factor.
PMID- 29948498
TI - Giraffe or leopard spot chorioretinopathy as an outstanding finding: case report
and literature review.
AB - PURPOSE: Presentation of two typical cases with characteristic leopard
retinopathy secondary to bilateral diffuse uveal melanocytic proliferation
(BDUMP) and idiopathic uveal effusion syndrome (IUES) and brief review of the
literature about leopard spot retinopathy. CASE REPORT: A 43-year-old women, who
was a known case of ovarian carcinoma, referred with gradual bilateral visual
loss. In ophthalmic examination, subretinal fluid, multiple patchy subretinal
hyperpigmented lesions and leopard spot chorioretinopathy were evident in her
both eyes. Fluorescein angiography showed multiple nummular hyperfluorescent
lesions surrounded by zones of hypofluorescence. Spectral domain optical
coherence tomography revealed increased retinal thickness, subretinal fluid and
RPE irregularities in both eyes. Enhanced depth imaging OCT (EDI-OCT) showed
bilateral subfoveal choroidal thickening. During next 2-year follow-up, she
underwent cataract surgery and later on developed neovascular glaucoma in her
both eyes. The second case was a 45-year-old man who had developed decreased
visual acuity in his left eye for 3 years. Anterior segment examination was
unremarkable, and both eyes had normal intraocular pressure. No vitreous
inflammation was observed. Fundoscopy revealed diffuse exudative retinal
detachment in his left eye. Fluorescein angiography showed leopard spot
retinopathy of posterior pole, and EDI-OCT disclosed subfoveal choroidal
thickening. After exclusion of other causes of exudative retinal detachment and
with diagnosis of IUES, he underwent intravitreal triamcinolone injection (2 mg)
which improved his final vision to 20/40. CONCLUSION: Leopard spot retinopathy is
an uncommon but clinically distinct manifestation of various disorders. BDUMP may
present with leopard spot retinopathy, anterior uveal tract involvement and
neovascular glaucoma. As EDI-OCT showed involvement and increased thickening of
choroid in both cases of BDUMP and IUES, it may be better to consider such cases
as leopard chorioretinopathy and categorize these entities as a member of
pachychoroid pigment retinopathy disorders.
PMID- 29948499
TI - Catching the therapeutic window of opportunity in early initial-onset Vogt
Koyanagi-Harada uveitis can cure the disease.
AB - PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune granulomatous
choroiditis that begins in the choroidal stroma. The aim of this review was to
gather a body of evidence for the concept of a window of therapeutic opportunity,
defined as a time interval following initial-onset disease during which adequate
treatment will substantially modify the disease outcome and possibly even lead to
cure, similar to what has been described for rheumatoid arthritis. METHODS: We
reviewed the literature and consulted leading experts in VKH disease to determine
the consensus for the notion of a therapeutic window of opportunity in VKH
disease. RESULTS: We found a substantial body of evidence in the literature that
a therapeutic window of opportunity exists for initial-onset acute uveitis
associated with VKH disease. The disease outcome can be substantially improved if
dual systemic steroidal and non-steroidal immunosuppressants are given within 2-3
weeks of the onset of initial VKH disease, avoiding evolution to chronic disease
and development of "sunset glow fundus." Several studies additionally report
series in which the disease could be cured, using such an approach. CONCLUSIONS:
There is substantial evidence for a therapeutic window of opportunity in initial
onset acute VKH disease. Timely and adequate treatment led to substantial
improvement of disease outcome and prevented chronic evolution and "sunset glow
fundus," and very early treatment led to the cure after discontinuation of
therapy in several series, likely due to the fact that the choroid is the sole
origin of inflammation in VKH disease.
PMID- 29948500
TI - Corneal stromal depth of the demarcation line in 'accelerated corneal cross
linking' with different concentrations of riboflavin solutions.
AB - PURPOSE: The aim of this study is to compare the effect of different riboflavin
solutions (hypotonic and isotonic) used during accelerated corneal cross-linking
(CXL) on the mean depth of the demarcation line (DDL) formed in corneal stroma.
METHODS: This prospective, cross-sectional study included 38 eyes of 26 patients.
All patients underwent accelerated CXL due to progressive keratoconus. When the
corneal epithelium was removed, 17 eyes of 12 patients with corneal thickness <
400 um were categorized as Group 1, and 21 eyes of 14 patients with corneal
thickness > 400 um as Group 2. Hypotonic riboflavin was applied to Group 1
patients, and isotonic riboflavin to Group 2 patients. Anterior segment optical
coherence tomography was performed on all patients by two independent observers
at the end of the first and third months. RESULT: Group 1 included 5 male and 7
female patients with an average age of 25.1 +/- 8.0 years, whereas Group 2
included 7 male and 7 female patients with an average age of 31.8 +/- 10.12
years. At the end of the first month, the mean DDL in Group 1 and Group 2 was
180.32 +/- 10.26 and 287.21 +/- 15.01 um, respectively. This difference was
statistically significant (p < 0.05). CONCLUSION: Application of different
riboflavin solutions was observed to have an effect on measured corneal thickness
after saturation and the depth of the demarcation line. The use of hypotonic
riboflavin results in swelling of the cornea and more superficial localization of
the stromal demarcation line after CXL.
PMID- 29948501
TI - Further observations on a bilateral IRVAN syndrome case.
AB - PURPOSE: Reporting clinical features of the late course of the disease after long
term follow-up in a bilaterally affected patient with idiopathic retinitis,
vasculitis, retinal aneurysms and neuroretinitis (IRVAN) and new peripheral
retinal findings on wide-field angiography and multimodal imaging. METHODS: This
was a retrospective observational study, based on current diagnostic studies
including wide-field fluorescein angiography, optical coherence tomography (OCT)
and treatment of aneurysms with argon laser photocoagulation. RESULTS: A 21-year
old female with bilateral IRVAN syndrome-stage 2 in the right eye and stage 3 in
the left eye-previously treated bilaterally with laser photocoagulation for
retinal macroaneurysms and ischemic areas between 1985 and 1992. Follow-up
interrupted on two occasions, with subsequent fundus re-examinations confirming
the prevention of retinal neovascularization in both eyes, as recently evidenced
on wide-field angiography. CONCLUSIONS: A case of bilateral IRVAN disease with
multiple retinal aneurysms, neuroretinitis and peripheral capillary nonperfusion
successfully treated with laser photocoagulation, maintaining normal visual
acuity in one eye and preventing retinal neovascular complications.
PMID- 29948503
TI - Prisoners' competence to die: hunger strike and cognitive competence.
AB - Several bioethicists have recently advocated the force-feeding of prisoners,
based on the assumption that prisoners have reduced or no autonomy. This assumed
lack of autonomy follows from a decrease in cognitive competence, which, in turn,
supposedly derives from imprisonment and/or being on hunger strike. In brief,
causal links are made between imprisonment or voluntary total fasting (VTF) and
mental disorders and between mental disorders and lack of cognitive competence. I
engage the bioethicists that support force-feeding by severing both of these
causal links. Specifically, I refute the claims that VTF automatically and
necessarily causes mental disorders such as depression, and that these mental
disorders necessarily or commonly entail cognitive impairment. Instead, I
critically review more nuanced approaches to assessing mental competence in
hunger strikes, urging that a diagnosis of incompetence be made on a case-by-case
basis-a position that is widely shared by the medical community.
PMID- 29948504
TI - Quantification of Inflammasome Adaptor Protein ASC in Biological Samples by
Multiple-Reaction Monitoring Mass Spectrometry.
AB - Inflammation is an integral component of many diseases, including chronic kidney
disease (CKD). ASC (apoptosis-associated speck-like protein containing CARD, also
PYCARD) is the key inflammasome adaptor protein in the innate immune response.
Since ASC specks, a macromolecular condensate of ASC protein, can be released by
inflammasome-activated cells into the extracellular space to amplify inflammatory
responses, the ASC protein could be an important biomarker in diagnostic
applications. Herein, we describe the development and validation of a multiple
reaction monitoring mass spectrometry (MRM-MS) assay for the accurate
quantification of ASC in human biospecimens. Limits of detection and
quantification for the signature DLLLQALR peptide (used as surrogate for the
target ASC protein) were determined by the method of standard addition using
synthetic isotope-labeled internal standard (SIS) peptide and urine matrix from a
healthy donor (LOQ was 8.25 pM, with a ~ 1000-fold linear range). We further
quantified ASC in the urine of CKD patients (8.4 +/- 1.3 ng ASC/ml urine, n =
13). ASC was positively correlated with proteinuria and urinary IL-18 in CKD
samples but not with urinary creatinine. Unfortunately, the ASC protein is
susceptible to degradation, and patient urine that was thawed and refrozen lost
85% of the ASC signal. In summary, the MRM-MS assay provides a robust means to
quantify ASC in biological samples, including clinical biospecimens; however,
sample collection and storage conditions will have a critical impact on assay
reliability.
PMID- 29948505
TI - Andrographolide Ameliorates Atherosclerosis by Suppressing Pro-Inflammation and
ROS Generation-Mediated Foam Cell Formation.
AB - Inflammation, oxidative stress, and dyslipidemia are major factors in the
pathogenesis of atherosclerosis. Andrographolide, a bioactive component of
Andrographis paniculata, has several biological activities, including anti
inflammatory, antioxidant, and anticancer effects. This study shows that
andrographolide downregulates the oxidized low-density lipoprotein (oxLDL)
induced expression of the pro-inflammatory molecules monocyte chemotactic protein
(MCP)-1 and interleukin (IL)-6 and blocks the nuclear factor-kappaB signaling
pathway in macrophages. Additionally, andrographolide treatment decreased
reactive oxygen species (ROS) generation in oxLDL-induced macrophages, indicating
that the compound can decrease oxidative stress. The results also suggest that
andrographolide suppresses oxLDL-induced foam cell formation and inhibits oxLDL
induced CD36 expression in vitro. Furthermore, in vivo studies have indicated
that andrographolide treatment ameliorates atherosclerosis pathogenesis in
apolipoprotein E knockout mice. Therefore, by suppressing inflammation, ROS
generation, and foam cell formation, andrographolide may ameliorate the
progression of atherosclerosis, suggesting its potential as a therapeutic drug
for the prevention and/or treatment of this disease.
PMID- 29948506
TI - Overexpression of ARNT2 is associated with decreased cell proliferation and
better prognosis in gastric cancer.
AB - Aryl hydrocarbon-receptor nuclear translocator (ARNT2) is a member of the bHLH
PAS (basic helix-loop-helix Period/ARNT/Single-minded) family of transcription
factors. Recently, some studies indicate that ARNT2 is associated with the
occurrence and development of carcinoma. However, its roles in gastric cancer
(GC) remain unclear. In the present study, we found that ARNT2 expression level
is lower in GC tissues compared with adjacent non-tumor tissues, and negatively
correlated with depth of invasion of the tumor, differentiated degree, and poor
survival of GC patients. Overexpression of ARNT2 inhibits cell proliferation.
Furthermore, AKT pathway contributed to ARNT2 -mediated PC proliferation. Taken
together, our results provide the first evidence that high expression of ARNT2
inhibited proliferation of GC cells and affected tumor aggressiveness in GC
patients.
PMID- 29948507
TI - Preventive effect on endothelial surface layer damage of Fusu agent in LPS
induced acute lung injury in rats.
AB - Acute lung injury (ALI) is one of major causes of morbidity and mortality in
intensive care. In pathophysiological events of ALI, endothelial surface layer
(ESL) injury can result in capillary leakage as the initial event. The "Fusu
agent", a traditional Chinese medicine, can inhibit inflammatory factors,
attenuate lung capillary leak as seen in our previous study. This study was aimed
to explore the molecular mechanism of Fusu agent treatment with ALI. Consistent
with previous studies, we found that Fusu agent has the protective effect on LPS
induced ALI model rats. Further investigation demonstrated that heparanase
activation is necessary for the LPS-induced ALI model to aggravate ESL loss. Fusu
agent can inhibit heparanase activation and heparan sulfate proteoglycans'
(HSPGs) degradation to mitigate the ESL injury. Furthermore, TNF-alpha and
intercellular adhesion molecule-1 (ICAM-1) were significantly reduced upon Fusu
agent pre-treatment to inhibit inflammatory cell influx and neutrophil adhesion
in ALI. These findings shed light on the pharmacologic basis for the clinical
application of traditional Chinese medicine in treating ALI.
PMID- 29948512
TI - Sex Differences in the Genetic and Environmental Influences on Self-Reported Non
aggressive and Aggressive Conduct Disorder Symptoms in Early and Middle
Adolescence.
AB - Decades of research into the etiology of conduct disorder (CD) has yet to yield a
consensus on the existence of sex differences in underlying genetic and
environmental influences. This may be partly due to the failure of many previous
studies to make a distinction between non-aggressive and aggressive CD symptoms
or test for potential developmental changes in sex differences in the etiology of
conduct problems. To address these gaps, we fit a series of univariate and
bivariate biometric sex-difference models to self-reported non-aggressive and
aggressive CD symptoms in a community-based sample of twins (N = 1548, ages 9-17
year), grouped into ages 9-13 and 14-17 years. Relative model fit was evaluated
using the Bayesian Information Criterion (BIC), which favors parsimony, and by
Chi square difference tests. The univariate sex-scalar model provided the best
fit to the data for both non-aggressive and aggressive CD symptoms at ages 9-13
and 14-17 years. Thus, the same genetic and environmental factors influenced CD
symptoms in both sexes, but the total variability was lower in females than
males. At both ages, the heritability of non-aggressive CD symptoms was lower
than heritability of aggressive CD symptoms, and shared environmental effects
were only observed for non-aggressive CD symptoms. However, estimates for genetic
and environmental factors could be not be constrained to be equal across age
groups for either CD subtype, suggesting substantive developmental changes in the
relative influence of genetic and environmental factors on individual differences
in CD symptoms. For both subtypes, the heritability was larger, and shared
environmental effect smaller, in the older age group than the younger age group.
A bivariate quantitative sex differences model provided the best fit to the data
at ages 9-13 years. Covariation between non-aggressive and aggressive CD symptoms
was due to overlapping shared and non-shared environmental factors in males and
females but the overall covariation was greater in males than females. In
contrast, at ages 14-17 years, the sex-scalar bivariate model provided the best
fit to the data, and covariation between non-aggressive and aggressive CD
symptoms was due to overlapping genetic and non-shared environmental factors.
Thus, the etiology of self-reported conduct disorder varied substantially by
symptom type and age. However, quantitative sex differences were only apparent
when the covariation between the two subtypes was considered.
PMID- 29948513
TI - Lactobacillus spp. impair the ability of Listeria monocytogenes FBUNT to adhere
to and invade Caco-2 cells.
AB - OBJECTIVES: The objective of this study was to evaluate the ability of
Lactobacillus curvatus CRL705, CRL1532, and CRL1533 and Lactobacillus sakei
CRL1613 to survive under simulated gastrointestinal conditions. Moreover, a
microencapsulation approach was proposed to improve gastrointestinal survival.
Finally, experiments were performed to demonstrate that Lactobacillus spp. can
modulate the ability of Listeria monocytogenes FBUNT to adhere to and invade Caco
2 cells. RESULTS: Lactobacillus strains were encapsulated in alginate beads to
enhance the survival of bacteria under in vitro gastrointestinal conditions. All
strains hydrolyzed bile salts using chenodeoxycholic acid as a substrate and
adhered to Caco-2 cells. Cell-free supernatants (CFSs) showed antimicrobial
activity against L. monocytogenes as demonstrated by agar diffusion assays. The
average percentages of L. monocytogenes adhesion decreased from 67.74 to 41.75
and 38.7% in the presence of 50 and 90% (v/v), respectively, for all CFSs tested.
The highest concentrations of CFSs completely inhibited the L. monocytogenes
invasion of Caco-2 cells. CONCLUSIONS: The studied Lactobacillus strains have
protective effects against the adhesion and invasion of L. monocytogenes FBUNT.
Alginate encapsulation of these bacteria improved gastrointestinal tolerance such
that they could be further studied as potential probiotics against intestinal
pathogenic bacteria.
PMID- 29948514
TI - Purification of active recombinant human histone deacetylase 1 (HDAC1)
overexpressed in Escherichia coli.
AB - OBJECTIVE: We attempted to overexpress Human Histone Deacetylase 1 (HDAC1) in
Escherichia coli. RESULTS: A synthetic gene coding for HDAC1, and optimised for
E. coli codon usage, was cloned into pBADHisB, generating pBAD-rHDAC1. This
construct was used to transform E. coli TOP10, and the target protein was
overexpressed and partially purified. According to its elution volume from a
Superdex 200 column, the partially purified rHDAC1 was obtained in aggregated
form, i.e., as an octamer. The dissociation of octameric HDAC1 was tested using
several agents, among which sodium dodecyl sulfate was competent in partially
dissociating rHDAC1 aggregates. When the enzyme activity was tested in vitro
using 3H-acetyl-labelled histones both protein samples, aggregated and
dissociated, were active. Hence, our results suggest that E. coli represents an
alternative system for the production of the recombinant HDAC1. CONCLUSIONS: We
described a procedure for the overexpression in E. coli of recombinant HDAC1, the
purification of which in active form can be successfully performed, although
yielding an octameric aggregate.
PMID- 29948515
TI - Gestational diabetes, type II diabetes, and mammographic breast density in a U.S.
racially diverse population screened for breast cancer.
AB - PURPOSE: Type II diabetes mellitus (T2DM) has consistently been associated with
an increased risk of breast cancer, but the association of gestational diabetes
mellitus (GDM) with breast cancer is less clear. T2DM and GDM may influence
breast cancer risk through mammographic breast density, a strong risk factor for
breast cancer. We examined whether T2DM and GDM are associated with higher
mammographic breast density in a largely racial/ethnic minority sample. METHODS:
We collected digital mammograms, anthropometric measures, and interview data from
511 racially diverse women recruited during screening mammography appointments
between 2012 and 2016 (mean age 51 years; 70% Hispanic). We examined the
associations of self-reported GDM, T2DM, and medication use (metformin and
insulin) with mammographic breast density, measured as percent and area of dense
tissue using Cumulus software. RESULTS: In multivariable linear regression
models, history of T2DM and/or GDM and length of time since diagnosis were not
associated with percent density or dense breast area, either before or after
adjustment for current BMI. Use of metformin in diabetic women was associated
with lower percent density (beta = - 5.73, 95% CI - 10.27, - 1.19), only before
adjusting for BMI. These associations were not modified by menopausal status.
CONCLUSIONS: Our results do not support associations between T2DM and/or GDM and
higher amount of mammographically dense breast tissue, suggesting that the
mechanism linking diabetes with breast cancer risk may not include mammographic
breast density in midlife.
PMID- 29948516
TI - Differences in smoking prevalence and eligibility for low-dose computed
tomography (LDCT) lung cancer screening among older U.S. adults: role of sexual
orientation.
AB - The purpose of this study was to determine the past-year prevalence estimates of
cigarette smoking and eligibility for low-dose computed tomography (LDCT) lung
cancer screening among older U.S. adults and examine potential variations in
these estimates by sexual orientation. Data were from the 2012-2013 National
Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) and included
in-person interviews with a nationally representative sample of non
institutionalized adults aged 18 and older. Eligibility for LDCT was based on
U.S. Centers for Medicare and Medicaid Services (CMS) guidelines. Analyses
included participants aged 55-77 (n = 9,635). Overall, 17.5% of older adult
respondents reported past-year smoking. Overall rates of past-year cigarette
smoking were influenced by sex and sexual orientation with males reporting higher
rates compared to females. Among both males and females, smoking was most
prevalent among bisexual individuals. Eligibility for LDCT was also higher among
males compared to females and among bisexually identified adults relative to
homosexual and heterosexual-identified adults. Overall, 11.2% of older U.S.
adults met eligibility for LDCT lung cancer screening. Eligibility for LDCT lung
screening is associated with sexual orientation; the highest rates of eligibility
are among bisexual women and men (26.9 and 24.5%, respectively). The current
study found variations in cigarette smoking and eligibility for LDCT lung cancer
screening (a proxy for chronic high-risk smoking) among older U.S. adults based
on sexual orientation. Efforts to increase screening should take into account
these differences.
PMID- 29948517
TI - Genomic prediction using an iterative conditional expectation algorithm for a
fast BayesC-like model.
AB - Genomic prediction is feasible for estimating genomic breeding values because of
dense genome-wide markers and credible statistical methods, such as Genomic Best
Linear Unbiased Prediction (GBLUP) and various Bayesian methods. Compared with
GBLUP, Bayesian methods propose more flexible assumptions for the distributions
of SNP effects. However, most Bayesian methods are performed based on Markov
chain Monte Carlo (MCMC) algorithms, leading to computational efficiency
challenges. Hence, some fast Bayesian approaches, such as fast BayesB (fBayesB),
were proposed to speed up the calculation. This study proposed another fast
Bayesian method termed fast BayesC (fBayesC). The prior distribution of fBayesC
assumes that a SNP with probability gamma has a non-zero effect which comes from
a normal density with a common variance. The simulated data from QTLMAS XII
workshop and actual data on large yellow croaker were used to compare the
predictive results of fBayesB, fBayesC and (MCMC-based) BayesC. The results
showed that when gamma was set as a small value, such as 0.01 in the simulated
data or 0.001 in the actual data, fBayesB and fBayesC yielded lower prediction
accuracies (abilities) than BayesC. In the actual data, fBayesC could yield very
similar predictive abilities as BayesC when gamma >= 0.01. When gamma = 0.01,
fBayesB could also yield similar results as fBayesC and BayesC. However, fBayesB
could not yield an explicit result when gamma >= 0.1, but a similar situation was
not observed for fBayesC. Moreover, the computational speed of fBayesC was
significantly faster than that of BayesC, making fBayesC a promising method for
genomic prediction.
PMID- 29948518
TI - Anaerobic ammonium oxidation linked to sulfate and ferric iron reduction fuels
nitrogen loss in marine sediments.
AB - Availability of fixed nitrogen is a pivotal driver on primary productivity in the
oceans, thus the identification of key processes triggering nitrogen losses from
these ecosystems is of major importance as they affect ecosystems function and
consequently global biogeochemical cycles. Denitrification and anaerobic ammonium
oxidation coupled to nitrite reduction (Anammox) are the only identified marine
sinks for fixed nitrogen. The present study provides evidence indicating that
anaerobic ammonium oxidation coupled to the reduction of sulfate, the most
abundant electron acceptor present in the oceans, prevails in marine sediments.
Tracer analysis with 15N-ammonium revealed that this microbial process, here
introduced as Sulfammox, accounts for up to 5 MUg 15N2 produced g-1 day-1 in
sediments collected from the eastern tropical North Pacific coast. Raman and X
ray diffraction spectroscopies revealed that elemental sulfur and sphalerite
(ZnFeS) were produced, besides free sulfide, during the course of Sulfammox.
Anaerobic ammonium oxidation linked to Fe(III) reduction (Feammox) was also
observed in the same marine sediments accounting for up to 2 MUg 15N2 produced g
1 day-1. Taxonomic characterization, based on 16S rRNA gene sequencing, of marine
sediments performing the Sulfammox and Feammox processes revealed the microbial
members potentially involved. These novel nitrogen sinks may significantly fuel
nitrogen loss in marine environments. These findings suggest that the
interconnections among the oceanic biogeochemical cycles of N, S and Fe are much
more complex than previously considered.
PMID- 29948519
TI - Aerobic bacteria degrading both n-alkanes and aromatic hydrocarbons: an
undervalued strategy for metabolic diversity and flexibility.
AB - Environmental pollution with petroleum toxic products has afflicted various
ecosystems, causing devastating damage to natural habitats with serious economic
implications. Some crude oil components may serve as growth substrates for
microorganisms. A number of bacterial strains reveal metabolic capacities to
biotransform various organic compounds. Some of the hydrocarbon degraders are
highly biochemically specialized, while the others display a versatile metabolism
and can utilize both saturated aliphatic and aromatic hydrocarbons. The extended
catabolic profiles of the latter group have been subjected to systematic and
complex studies relatively rarely thus far. Growing evidence shows that numerous
bacteria produce broad biochemical activities towards different hydrocarbon types
and such an enhanced metabolic potential can be found in many more species than
the already well-known oil-degraders. These strains may play an important role in
the removal of heterogeneous contamination. They are thus considered to be a
promising solution in bioremediation applications. The main purpose of this
article is to provide an overview of the current knowledge on aerobic bacteria
involved in the mineralization or transformation of both n-alkanes and aromatic
hydrocarbons. Variant scientific approaches enabling to evaluate these features
on biochemical as well as genetic levels are presented. The distribution of
multidegradative capabilities between bacterial taxa is systematically shown and
the possibility of simultaneous transformation of complex hydrocarbon mixtures is
discussed. Bioinformatic analysis of the currently available genetic data is
employed to enable generation of phylogenetic relationships between environmental
strain isolates belonging to the phyla Actinobacteria, Proteobacteria, and
Firmicutes. The study proves that the co-occurrence of genes responsible for
concomitant metabolic bioconversion reactions of structurally-diverse
hydrocarbons is not unique among various systematic groups.
PMID- 29948520
TI - PortSmouth TAble Rotation Robotic technique for pan proctocolecotmy using DaVinci
Si robotic system; P-STARR technique.
PMID- 29948521
TI - Correction to: Distal Doppler-guided transanal hemorrhoidal dearterialization
with mucopexy versus conventional hemorrhoidectomy for grade III and IV
hemorrhoids: postoperative morbidity and long-term outcomes.
AB - The article "Distal Doppler-guided transanal hemorrhoidal dearterialization with
mucopexy versus conventional hemorrhoidectomy for grade III and IV hemorrhoids:
postoperative morbidity and long-term outcomes", written by L. Trenti, S. Biondo,
A. Galvez, A. Bravo, J. Cabrera, E. Kreisler, was originally published
electronically on the publisher's internet portal (currently SpringerLink) on [27
April 2017] without open access. With the author(s)' decision to opt for Open
Choice the copyright of the article changed on 7 June, 2018 to
PMID- 29948522
TI - Damage control surgery in patients with generalized peritonitis secondary to
perforated diverticulitis: the risk of overtreatment.
PMID- 29948523
TI - Left colon resection with transrectal specimen extraction: current status.
AB - BACKGROUND: Full laparoscopic left colectomy with transrectal specimen extraction
is proposed as an improvement of the minimally invasive surgical technique. This
paper reviews in detail the current status of left-sided colectomy and upper
rectum resection with transrectal specimen extraction. METHODS: A systematic
review was performed of all types of publications on colorectal resection with
natural orifice specimen extraction (NOSE). We only included studies reporting on
left colectomy, sigmoidectomy, and high anterior resection with transrectal
specimen extraction (TRSE), excluding transanal (TASE), transvaginal, or
transcolonic specimen extraction. Surgical techniques, patient characteristics,
and outcomes were reviewed in detail. RESULTS: Thirty-five papers reported on
TRSE (2 randomized clinical trials, 7 case-matched series, 19 case series, 5 case
reports, and 2 articles on surgical technique). We found a wide variety of
innovative anastomotic and specimen extraction techniques. After excluding
duplicates and papers reporting mixed TRSE and TASE results, outcomes in patients
undergoing TRSE from 23 publications showed a conversion rate to conventional
laparoscopy of 3.7% (21/559), overall morbidity 9.5% (53/559) [major in 2.9%
(16/559), intra-abdominal infection in 2.1% (12/559)]. No mortality was reported.
Postoperative anal incontinence was rarely reported. Several studies showed a
decrease in postoperative pain and some in length of hospital stay. CONCLUSIONS:
Colectomy with TRSE is feasible and seems safe in selected patients. Reported
outcomes seem in general similar to conventional laparoscopic colectomy with a
possible benefit in postoperative pain and length of hospital stay. Obvious
selection bias and lack of high quality trials do not allow firm conclusions to
be drawn.
PMID- 29948524
TI - Pit Latrines: A Noninvasive Sampling Strategy to Assess Fecal Pathogen Occurrence
in Low Resource Communities.
AB - Limited understanding of disease in low resource communities continues to hamper
improvements in health. We evaluated household pit latrine sampling as a non
invasive approach to investigate important fecal pathogens such as Giardia
lamblia and Cryptosporidium spp. in impoverished communities where health-seeking
behavior limits the sensitivity of health facility-based surveillance. Fecal
samples were collected from pit latrines in randomly selected households and from
patients presenting to the only hospital in the region during the same time
periods. Samples were tested with a commercially available ELISA. Giardia
household prevalence was 28.7% in 2016 and 48.4% in 2017, while individual
samples from hospital submission had a Giardia prevalence of 2.4% in 2016 and
8.0% in 2017. Cryptosporidium was only found in one household. Results suggest
that pit latrine surveillance for fecal-borne infections provide course estimates
of community infection levels that are unbiased by health seeking behaviors and
allow surveillance of vulnerable sectors of a population.
PMID- 29948527
TI - Perceptions of Family Problems and Pessimism Among Latina and Non-Latina White
Mothers Raising Children with Autism Spectrum Disorder.
AB - To address the limited research on diverse families of children with ASD, we
examined the impact of ASD on 46 Latina and 56 non-Latina White mothers from a
resiliency perspective. We explored perceptions of family problems, optimism and
pessimism among mothers of child with ASD between 1 and 22 years old. Mothers
were recruited through support groups and listservs. Univariate and multivariate
analyses were conducted. Results indicated fewer perceived family problems and
less pessimism about the child's future among Latina mothers. We found maternal
optimism and family cohesion were associated with perceived family problems and
mother's pessimism about the child's future. Understanding the impact of ASD
among diverse families will aid in developing appropriate services that enhances
family strengths.
PMID- 29948528
TI - Brief Report: A Gaming Approach to the Assessment of Attention Networks in Autism
Spectrum Disorder and Typical Development.
AB - Attentional impairments are among the earliest identifiable features of autism
spectrum disorders (ASDs). Three attention networks have been extensively studied
using the attention network test (ANT), but this long and repetitive task may
pose challenges for individuals with ASDs. The AttentionTrip was developed as a
more engaging measure of attention network efficiency. In 20 adults with ASDs and
20 typically developing controls, both tasks produced typical network scores (all
p < .003, all Cohen's d > 0.78). Reaction time was less variable in the
AttentionTrip than the ANT, possibly reflecting improved task engagement.
Although the AttentionTrip elicited more consistent responses throughout an
experimental session, anomalously low split-half reliability for its executive
control network suggests that some changes may be needed.
PMID- 29948526
TI - Barriers to Care in Chinese Immigrants with Hepatocellular Carcinoma: A Focus
Group Study in New York City.
AB - The incidence of hepatocellular carcinoma (HCC) is rising sharply in the United
States and deaths from HCC have increased at the highest rate of all cancers.
Though Asians have the highest incidence of HCC of all ethnicities in the US,
racial/ethnic minorities, including Asians, have worse survival from HCC. We
sought to identify barriers to care in treatment of HCC among affected
individuals in the NYC Chinese immigrant community. We held focus groups with
Chinese immigrant patients in NYC with HCC. 29 individuals participated in the
focus groups. We analyzed focus group data using grounded theory methodology.
Barriers to care identified included insurance, money, time, language, residency
status, and stigma. The impact of provider bias and culture were also discussed.
Knowledge gathering with minority patients with HCC is essential for us to fully
comprehend the barriers to healthcare experienced by this community. Future
policy and intervention efforts must be founded in this reality.
PMID- 29948525
TI - South Asian Cardiovascular Disease & Cancer Risk: Genetics & Pathophysiology.
AB - South Asians (SAs) are at heightened risk for cardiovascular disease as compared
to other ethnic groups, facing premature and more severe coronary artery disease,
and decreased insulin sensitivity. This disease burden can only be partially
explained by conventional risk factors, suggesting the need for a specific
cardiovascular risk profile for SAs. Current research, as explored through a
comprehensive literature review, suggests the existence of population specific
genetic risk factors such as lipoprotein(a), as well as population specific gene
modulating factors. This review catalogues the available research on
cardiovascular disease and genetics, anthropometry, and pathophysiology, and
cancer genetics among SAs, with a geographical focus on the U.S. A tailored risk
profile will hinge upon population customized classification and treatment
guidelines, informed by continued research.
PMID- 29948529
TI - A Longitudinal Study of Children Diagnosed with Autism Spectrum Disorder Before
Age Three: School Services at Three Points Time for Three Levels of Outcome
Disability.
AB - This study follows 70 children determined to have Autism Spectrum Disorder (ASD)
before age three (Time 1). Parents filled out questionnaires and standardized
measures about their child when he/she was school-aged (Time 2), including
information about their children's preschool, kindergarten, and grade school
educational settings. At Time 2, the researchers placed children in three
diagnostic groups of No ASD, ASD-Higher Functioning, and ASD-Lower Functioning.
Retrospective results showed that most children were receiving intensive services
at the preschool level. In kindergarten, there was some divergence among the
three groups, with more intensive services continuing for the ASD groups. At
school age, classroom placement and services reflected service patterns that were
consistent with these three levels of disability.
PMID- 29948530
TI - Autism Diagnosis in the United Kingdom: Perspectives of Autistic Adults, Parents
and Professionals.
AB - Accessing an autism diagnosis is a key milestone, both for an individual and
their family. Using a qualitative methodology, the current study examined the
views and experiences of ten autistic adults, ten parents of children on the
autism spectrum, and ten professionals involved in autism diagnosis, all based in
the United Kingdom (UK). Interviewing these 30 respondents about the diagnostic
process and subsequent support options, the goal was to identify aspects of the
diagnostic process that are working well, and areas in which improvements are
needed. Using thematic analysis, three key themes were identified: the process of
understanding and accepting autism; multiple barriers to satisfaction with the
diagnostic process; and inadequate post-diagnostic support provision.
PMID- 29948531
TI - Maternal Alcohol Consumption During Pregnancy and the Risk of Autism Spectrum
Disorders in Offspring: A Retrospective Analysis of the Millennium Cohort Study.
AB - The objective of this retrospective analysis of the longitudinal Millennium
Cohort Study was to examine whether maternal alcohol consumption in pregnancy
(MACP) is associated with the development of childhood autism spectrum disorders
(ASD). Data on MACP and ASD were obtained from parental questionnaires. There
were 18,168 singleton mother-child pairs with data on MACP, and 12,595 answered
the question on ASD when the children were 11 years old. No statistically
significant association was found between MACP and ASD for light (OR 0.78, 95% CI
0.48-1.29), moderate (OR 0.89, 95% CI 0.35-2.27), or heavy (OR 1.54, 95% CI 0.56
4.21) MACP. Alcohol consumption during pregnancy was not associated with the risk
of developing ASD in this study cohort.
PMID- 29948532
TI - Brief Report: The Impact of Sensory Hypersensitivity and Intolerance of
Uncertainty on Anxiety in Williams Syndrome.
AB - This study explored the interrelationship between intolerance of uncertainty,
sensory hyper-sensitivity and anxiety in Williams syndrome (WS). Thirty-two
parents or guardians of individuals with WS (Mage = 24.76 years, SD = 7.55) were
included. Associations between anxiety, intolerance of uncertainty, sensory hyper
sensitivity, and ASD symptoms were assessed. Linear regression analysis revealed
that intolerance of uncertainty and sensory hyper-sensitivity were unique
independent predictors of anxiety, while social communication score was not.
There was evidence of a mediating effect of sensory hyper-sensitivity on the
relationship between intolerance of uncertainty and anxiety. These findings bear
strong resemblance to the pattern seen in ASD and emphasize the need for
development of anxiety interventions that attempt to reduce negative beliefs
about unpredictable situations in WS.
PMID- 29948533
TI - Brief Report: A Survey of Autism Research Priorities Across a Diverse Community
of Stakeholders.
AB - Inclusion of stakeholder voices in the allocation of research funding can
increase the relevance of results and improve community engagement in research.
We describe the results of an online survey that gathered input from community
stakeholders regarding autism research priorities. A demographically diverse
sample of respondents (N = 6004; 79.1% female; 72.5% ages 30-59; 86.4% USA)
completed the survey. Results indicated a preference for applied relative to
basic science topics, though both basic and applied science areas were rated as
important. Respondents gave their highest ratings to research focused on co
occurring conditions, health and well-being, adult transition, and lifespan
issues. These results can guide decision-making by public and private funders
when developing science funding priorities and engaging in science dissemination
activities.
PMID- 29948534
TI - Biochar reduces cadmium accumulation in rice grains in a tungsten mining area
field experiment: effects of biochar type and dosage, rice variety, and pollution
level.
AB - Cadmium (Cd)-contaminated rice (Oryza sativa) in Southern China is a great threat
to food security, and the paddy soil remediation is urgently needed to reduce Cd
accumulation in rice. Application of biochar could effectively immobilize soil Cd
and reduce Cd uptake by rice. Fields that were applied with soil treatments
including control and 15 and 30 t ha-1 each hickory nut shell-derived biochar
(KC) or maize straw-derived biochar (MC), and grown with two rice varieties
(hybrid rice and late japonica rice) were selected for this study. The long-term
effect of biochars on decreasing Cd bioavailability in paddy soils was evaluated.
The results showed when MC was applied at 15 t ha-1, DTPA-Cd (soil cadmium
extracted by diethylenetriamine pentaacetic acid) was reduced by 20.0 and 34.5%
in Field A (slightly Cd pollution) and B (moderately Cd pollution), respectively.
In Field B, soil DTPA-Cd concentrations with application of 30 t ha-1 biochars
were all lower than that of 15 t ha-1 biochar, but there were no significant
differences between the two types of biochars. Cd concentration in rice grains
and straws of hybrid rice are two times more than those of late japonica rice. Cd
bio-concentration factor both of grains and straw was significantly increased by
biochar application, which in Field A was higher than that in Field B. Our
results suggest that biochars reduce Cd accumulation in rice grains by
immobilizing soil Cd. KC has a higher potential in lowering Cd bioavailability
than MC. Hybrid rice should be prohibited to cultivate in these areas.
PMID- 29948535
TI - Leaching of polycyclic aromatic hydrocarbons (PAHs) from coal dumps reclaimed
with apple trees: a mechanistic insight.
AB - Polycyclic aromatic hydrocarbons (PAHs) have been identified as compounds that
can be incorporated to run-off waters or to aquifers becoming a real threat not
only to aquatic organisms but also to humans due to its carcinogenic and
mutagenic activity. This work studies the presence of PAHs in a coal dump pile
located in the north of Spain (Asturias), downhill a spoil pile of a cinabrium
mine. This unique site gives the opportunity to assess whether acid waters have
more potential to leach PAHs than normal rainwater (acidified when it gets in
contact with coal spoil). The distribution of PAHs and methyl PAHs has shown that
their abundance is higher in the path of acid waters which could be caused by the
ability of acid water to break bonds of coal macromolecules. This chemical
reaction liberates PAHs of less molecular weight that can be detected by GC-MS.
Moreover, less soluble PAHs are concentrated on the acid water circulation area
and more soluble PAHs more leached by acid water that rainwater, which indicates
that PAHs dissolve more in acid waters than in normal rainwater. In addition,
this coal spoil pile has been reclaimed with apple trees to make cider for human
consumption. Up to 152 different compounds were identified in the tree samples,
but neither PAHs nor methyl PAHs were found, pointing to a possible retention of
the PAHs in the roots zone. Apple trees in the acid waters path show more
concentration in waxes and flavour compounds, indicating a more mature apple.
PMID- 29948536
TI - On the rubidium and lithium content and availability in the sub-arid south
eastern Mediterranean: potential health implications.
AB - Rubidium and lithium are rather rare elements in environmental research, despite
their affiliation with a group of chemically active metals and the abundance of
Rb in the environment. A growing body of evidence, although controversial, has
indicated that both elements possess unique essential and neurophysiological
characteristics in biota and humans. Both elements may concentrate in soil and
vegetation of sub-arid environments. We investigated the content and (potential)
availability of Rb and Li in the soils and natural waters of Galilee, the Coastal
Plain, and the northern Negev of Israel. A newly developed chromatographic
technique for the separation of truly dissolved Rb and Li compounds has been
applied. High concentrations of Rb, together with high values of the potentially
vital Rb-to-K ratio, were found in the soils, the soil solutions, rainwater,
throughfall water, and the plant litter leachates, but not in the surface and
spring waters. This may indicate a sequestration of Rb in the local soils and a
semi-closed Rb turnover in the soil-plant system with a major input from sea
aerosols. Low Li bulk and available concentrations were determined in all the
natural compartments. Possible implications of such specific environmental
features on the local population health were discussed.
PMID- 29948537
TI - Geochemical valuation and intake of F, As, and Se in coal wastes contaminated
areas and their potential impacts on local inhabitants, Shaanxi China.
AB - This study probe the human health risk of fluoride (F), arsenic (As), and
selenium (Se) and their daily intake available quantity to human through
different sources in different regions of Shaanxi, China. For this purpose, a
number of samples, including coal and coal wastes, rocks, soil, and vegetables
were collected from south Qinling Mountain stone-like coal (Geo type-I), Binxian
Jurassic (Geo type-II), Hancheng Permo-Carboniferous (Geo type-III), and
countryside (Huanglong County) of Shaanxi province. All these samples were
analyzed through atomic fluorescence spectroscopy and combustion hydrolysis
methods. Results showed that Geo type-I was enriched with As, Se, and F, Geo type
II, III, and the countryside were slightly enriched with As and F and deficient
in Se. The average daily intake (ADI) of Se in Geo type-I was 0.005-0.0045, Geo
type-II 0.0005-0.0004, Geo type-III 0.0006-0.0005, and countryside 0.0002-0.001
in mg kg-1 day-1 adult-children, respectively, which was lower than the optimum
level (0.06-0.075 mg kg-1day-1). ADI of As at Geo type-I was 0.0085-0.0075, Geo
type-II 0.004-0.0037, Geo type-III 0.0008, and countryside 0.00022-0.00019 in mg
kg-1 day-1 adult-children, respectively, which was above the acceptable range (10
6-10-4). ADI of F at Geo type-I was 0.0047-0.0041, Geo type-II 0.0098-0.0087, Geo
type-III 0.002-0.0017 and countryside 0.0015-0.0013 in mg kg-1 day-1 adult
children, respectively. The toxicity level of Se and F at all the regions was
lower than the NOAEL and LOAEL, while As was higher at Geo type-II and I. The
extreme deficient of Se than the optimum range along with high F could deregulate
the normal body growth especially causes bones and joint problems. However, the
study found a rare patient with bone and joint disease (maybe Kashin-Beck
disease) in the countryside. To find the exact cause of Kashin-Beck disease, the
study needs further medical investigation in Se-deficient regions and their
association with selenium deficiency and enriched fluoride.
PMID- 29948538
TI - A follow-up study of the development of skin lesions associated with arsenic
exposure duration.
AB - Little information about the development of skin lesions in relation to arsenic
exposure duration is available. Therefore, skin lesions in a cohort from the
Bameng region of China were diagnosed in 2012 and 2017. The results indicated
that the prevalence of hyperkeratosis, pigmentation and depigmentation in 2017
was 64.67, 6.67 and 12.67%. There were 42 and 34% of male subjects and female
subjects suffered from skin lesions in 2012. Their morbidity rates were 10.43 and
8.98 per 1000 person-years. In 2017, the values were significantly increased. The
prevalence and morbidity rate of skin lesions were positively correlated with age
and arsenic levels in drinking water. Males had higher prevalence of skin lesions
compared with female. However, the <= 40 years female group had higher prevalence
of skin lesions. In addition, the increased rate of skin lesions prevalence was
negatively correlated with arsenic levels in drinking water. The odds ratios
(ORs) showed that the risks of skin lesions were positively associated with the
proportion of inorganic arsenic (%iAs) and monomethylarsonic acid (%MMA) in
urine, and negatively correlated with arsenic methylation capacity in both 2012
and 2017. It can be concluded that females immigrated from other areas were more
susceptible to developing skin lesions. A certain cumulative arsenic exposure
dose, which may be existing, significantly increased the prevalence of skin
lesions. Longer arsenic exposure duration might elevate the toxicity of iAs to
skin lesions and reduce the positive effects of arsenic methylation capacity on
skin lesions.
PMID- 29948539
TI - Magnetic chitosan/sodium alginate gel bead as a novel composite adsorbent for
Cu(II) removal from aqueous solution.
AB - Using sodium alginate hydrogel as skeleton, in combination with chitosan and
magnetic Fe3O4, a new type of magnetic chitosan/sodium alginate gel bead (MCSB)
was prepared. Adsorptive removal of Cu(II) from aqueous solutions was studied by
using the MCSB as a promising candidate in environmental application. Different
kinetics and isotherm models were employed to investigate the adsorption process.
Based on Fourier transform infrared spectroscopy, field-emission scanning
electron microscope, CHNS/O elements analysis, vibration magnetometer, and
various means of characterization, a comprehensive analysis of the adsorption
mechanism was conducted. The MCSB had a good magnetic performance with a
saturation magnetization of 12.5 emu/g. Elemental analysis proved that the
addition of chitosan introduced a considerable amount of nitrogen-rich groups,
contributing significantly to copper adsorption onto gel beads. The contact time
necessary for adsorption was optimized at 120 min to achieve equilibrium.
Experimental data showed that the adsorption process agreed well with the
Langmuir isotherm model and the pseudo-second-order kinetics model. The
theoretical maximum adsorption capacity of MCSB for Cu(II) could reach as high as
124.53 mg/g. In conclusion, the MCSB in this study is a novel and promising
composite adsorbent, which can be applied for practical applications in due
course.
PMID- 29948540
TI - Contraction of collecting lymphatics: organization of pressure-dependent rate for
multiple lymphangions.
AB - The paper describes the extension of a previously developed model of pressure
dependent contraction rate to the case of multiple lymphangions. Mechanical
factors are key modulators of active lymphatic pumping. As part of the evolution
of our lumped-parameter model to match experimental findings, we have designed an
algorithm whereby the time until the next contraction depends on lymphangion
transmural pressure in the contraction just completed. The functional dependence
of frequency on pressure is quantitatively matched to isobaric contraction
experiments on isolated lymphatic segments. When each of several lymphangions is
given this ability, a scheme for their coordination must be instituted to match
the observed synchronization. Accordingly, and in line with an experiment on an
isolated lymphatic vessel segment in which we measured contraction sequence and
conduction delay, we took the fundamental principle to be that local timing can
be overridden by signals to initiate contraction that start in adjacent
lymphangions, conducted with a short delay. The scheme leads to retrograde
conduction when the lymphangion chain is pumping against an adverse pressure
difference, but antegrade conduction when contractions occur with no or a
favourable pressure difference. Abolition of these conducted signals leads to
chaotic variation of cycle-mean flow-rate from the chain, diastolic duration in
each lymphangion, and inter-lymphangion delays. Chaotic rhythm is also seen under
other circumstances. Because the model responds to increasing adverse pressure
difference by increasing the repetition rate of contractions, it maintains time
average output flow-rate better than one with fixed repetition rate.
PMID- 29948541
TI - Self-compassion, chronic age-related stressors, and diurnal cortisol secretion in
older adulthood.
AB - Many older adults experience chronic age-related stressors (e.g., life regrets or
health problems) that are difficult to control and can disturb cortisol
regulation. Self-compassion may buffer adverse effects of these stressful
experiences on diurnal cortisol secretion in older adulthood. To examine whether
self-compassion could benefit older adults' cortisol secretion in the context of
chronic and largely uncontrollable age-related stressors, 233 community-dwelling
older adults reported their levels of self-compassion, age-related stressors
(regret intensity, physical health problems, and functional disability), and
relevant covariates. Diurnal cortisol was measured over 3 days and the average
area-under-the-curve and slope were calculated. Higher levels of self-compassion
were associated with lower daily cortisol levels among older adults who reported
higher levels of regret intensity, physical health problems, or functional
disability (betas < - .53, ps < .01), but not among their counterparts who
reported lower levels of these age-related stressors (betas < .24, ps > .28).
These results suggest that self-compassion may represent an important personal
resource that could protect older adults from stress-related biological
disturbances resulting from chronic and uncontrollable stressors.
PMID- 29948542
TI - Longitudinal relationship between onset of physical symptoms and functional
impairment.
AB - Patients with chronic physical symptoms (e.g., chronic pain) often have
significant functional impairment (i.e., disability). The fear avoidance model is
the dominant theoretical model of how the relationship between chronic physical
symptoms and functional impairment develops and proposes a cyclical/bidirectional
relationship. There has never been a definitive test of the proposed bi
directional relationship. The current study followed 767 Operation Enduring
Freedom/Operation Iraqi Freedom soldiers from pre-deployment, when they were
relatively healthy, to 1 year after deployment, when it was anticipated that
symptoms would increase or develop. Over the four assessment time points,
physical symptom severity consistently predicted worse functional impairment at
the subsequent time point. Functional impairment did not show a consistent
relationship with worsening of physical symptom severity. These findings suggest
that changes to functional impairment do not have a short-term impact on physical
symptom severity.
PMID- 29948544
TI - Correction: Gut-Associated Bacteria of Helicoverpa zea Indirectly Trigger Plant
Defenses in Maize.
AB - The original version of this article unfortunately contained a mistake. Fig. 3
and Fig. 4a were identical and the original version of Fig. 4a had been
accidentally replaced.
PMID- 29948543
TI - Biochemical Analyses of Proteins from Duttaphrynus melanostictus (Bufo
melanostictus) Skin Secretion: Soluble Protein Retrieval from a Viscous Matrix by
Ion-Exchange Batch Sample Preparation.
AB - A crucial step in scientific analysis can be sample preparation, and its
importance increases in the same rate as the sensitivity of the following
employed/desired analytical technique does. The need to analyze complex, viscous
matrices is not new, and diverse approaches have been employed, with different
success rates depending on the intended molecules. Solid-phase extraction, for
example, has been successfully used in sample preparation for organic molecules
and peptides. However, due to the usual methodological conditions, biologically
active proteins are not successfully retrieved by this technique, resulting in a
low rate of protein identification reported for the viscous amphibian skin
secretion. Here we describe an ion-exchange batch processing sample preparation
technique that allows viscous or adhesive materials (as some amphibian skin
secretions) to be further processed by classical liquid chromatography
approaches. According to our protocol, samples were allowed to equilibrate with a
specific resin that was washed with appropriated buffers in order to yield the
soluble protein fraction. In order to show the efficiency of our methodology, we
have compared our results to classically prepared skin secretion, i.e., by means
of filtration and centrifugation. After batch sample preparation, we were able to
obtain reproductive resolved protein chromatographic profiles, as revealed by SDS
PAGE, and retrieve some biological activities, namely, hydrolases belonging to
serine peptidase family. Not only that, but also the unbound fraction was rich in
low molecular mass molecules, such as alkaloids and steroids, making this sample
preparation technique also suitable for the enrichment of such molecules.
PMID- 29948545
TI - 99mTc-GSA SPECT/CT fusion imaging for hepatectomy candidates with extremely
deteriorated ICG value.
AB - PURPOSE: The value of indocyanine green (ICG) test is negatively affected in
patients with intrahepatic shunt, ICG excretory defect, or jaundice. This study
evaluated 99mTc-GSA SPECT/CT fusion imaging for assessing liver function in
patients with severely deteriorated ICG values. MATERIALS AND METHODS: Thirteen
hepatectomy candidates with ICG retention rates over 40% were retrospectively
analyzed. The ICG clearance rate (KICG) and estimated KICG obtained by 99mTc-GSA
scintigraphy (KGSA) were used to evaluate preoperative whole liver function.
Remnant liver function was assessed using the remnant (rem) KICG (= KICG *
volumetric rate) and remKGSA (= KGSA * functional rate) indices; hepatectomy was
considered unsafe for values < 0.05. The correlations of remKICG and remKGSA with
postoperative mortality and morbidity were also investigated. RESULTS: KGSA
values were significantly greater than KICG values (median: 0.12 vs. 0.059; p <
0.01); remKGSA values were greater than remKICG values in all patients (median:
0.107 vs. 0.0413; p < 0.01). Hepatectomy was considered unsafe in 70% patients
using remKICG, and in none of those using remKGSA; liver failure or postoperative
mortality did not occur. CONCLUSIONS: 99mTc-GSA SPECT/CT fusion imaging enables
more accurate liver function assessment than the ICG test in patients with
severely deteriorated ICG values.
PMID- 29948546
TI - High contrast between lumbar nerve roots and surrounding structures using dual
echo 3D turbo spin echo additional fusion images.
AB - PURPOSE: We performed lumbar spinal magnetic resonance imaging of three
dimensional (3D) dual echo volumetric isotropic turbo spin echo acquisition (DE
VISTA) and constructed DE-VISTA additional fusion images (DE-VISTA-AFI), which is
the addition of DE-VISTA proton density-weighted images (DE-VISTA-PDWI) to DE
VISTA T2-weighted images (DE-VISTA-T2WI). The aim of this study was to clarify
whether DE-VISTA-AFI was able to clearly delineate spinal nerve roots. METHODS: A
total of 677 patients underwent lumbar MR imaging, and the signal ratio (SR)
between cerebrospinal fluid and nerve roots inside the dural sac and the SR
between fat and nerve roots outside the dural sac were estimated using DE-VISTA
AFI, DE-VISTA-PDWI, DE-VISTA-T2WI, and 2D-T2WI. RESULTS: The SR between
cerebrospinal fluid and nerve roots inside the dural sac on DE-VISTA-AFI was
higher than that on DE-VISTA-PDWI (p < 0.0001) and on 2D T2WI (p < 0.0001). The
SR between the fat tissue and nerve roots outside the dural sac on DE-VISTA-AFI
was higher than that on DE-VISTA-PDWI (p < 0.0001) and 2D T2WI (p < 0.0001).
CONCLUSION: DE-VISTA-AFI could clearly delineate the entire length of the lumbar
nerve roots that run from the cauda equina in the spinal fluid through to the fat
in the lateral recess, intervertebral foramen, and outside the intervertebral
foramen.
PMID- 29948547
TI - Simple quantification of paracardial and epicardial fat dimensions at low-dose
chest CT: correlation with metabolic risk factors and usefulness in predicting
metabolic syndrome.
AB - PURPOSE: To assess the usefulness of simple axial bi-dimensional diameters of
pericardial fat tissues at low-dose chest CT, in correlation with metabolic
parameters in predicting metabolic syndrome. MATERIALS AND METHODS: Subjects were
373 asymptomatic individuals who performed both low-dose chest CT and abdominal
fat CT for medical check-up. Maximum bi-dimensional axial diameters of
paracardial fats at right (RPF) and left (LPF) cardiophrenic angle portions, and
epicardial fats around right (REF) and left (LEF) coronary arteries, and coronary
sinus (SEF) were measured. Correlation between pericardial fat diameters and
metabolic parameters were statistically analyzed. RESULTS: RPF, LPF, REF, LEF,
and SEF diameters were moderately correlated with abdominal visceral fat (AVF)
area (R = 0.74, 0.70, 0.48, 0.41, and 0.53, respectively, p < 0.01) in Pearson's
correlation analysis. In multiple linear regression analysis, coefficient of RPF
for AVF showed highest value. Means of each PF and EF diameters in subjects with
metabolic syndrome were significantly larger than those without metabolic
syndrome (p < 0.001). All PF and EF diameters were well-discriminated for
prediction of metabolic syndrome in ROC analysis (AUC values, from 0.696 to
0.795). CONCLUSION: RPF diameter at low-dose chest CT would be a simple method
for prediction of metabolic syndrome.
PMID- 29948548
TI - The pathology of soft tissue sarcomas.
AB - Soft tissue sarcomas represent a heterogeneous group of rare malignancies
exhibiting mesenchymal differentiation with an overall incidence of around
5/100,000/year. Rarity and morphologic heterogeneity significantly affect
diagnostic accuracy; therefore, expertise can be achieved only through access to
large number of cases. Soft tissue sarcomas are currently classified on the basis
of the 2013 WHO classification of soft tissue tumors that integrate conventional
morphology with immunohistochemistry and molecular genetics. The morphologic
diagnosis of sarcoma relies on the evaluation as well as the integration of four
main features: the shape of the neoplastic cells; the pattern of growth; the
quality of the background; the architecture of the vascular network.
Immunohistochemical characterization plays a key role in the diagnostic workup of
soft tissue sarcomas. The majority of classic differentiation markers tend to
show good sensitivity, however, associated with rather limited specificity,
making interpretation in context with morphology mandatory. Molecular genetics is
increasingly used for diagnostic purposes to distinguish specific subtypes of
sarcomas, to support diagnosis in non-canonical clinical presentations and also
to distinguish true sarcomas from benign mimickers. With many exceptions,
histologic typing does not provide sufficient information for predicting the
clinical course of the disease and, therefore, grading systems based on
histological parameters were introduced to provide a more accurate estimation of
the degree of malignancy of tumors. The three-tiered system devised by the French
Federation of Cancer Centers Sarcoma Group (FNCLCC) systems is widely adopted;
however, several limitations exist that have led to the development of prognostic
nomograms that incorporate the specific histotype as one of the relevant
parameters.
PMID- 29948549
TI - Establishment and characterization of rough-tailed gecko original tail cells.
AB - Some of lizard species have the ability to lose their tail in order to defend
against predators and regenerate the new tail. Lizard's regenerated tail has
attracted scientists' attention for unraveling the regeneration process, but less
information is known about the cellular characterization and cell growth
properties of original tail. This research aimed to report cell culture and
banking process of rough-tailed gecko or Cyrtopodion scabrum's original tail cell
sample from inner tissue without skin using tissue explant technique. For banking
reports, it is essential to analyze this cells' potential to proliferate, to
investigate biological aspects such as cell culture features, differentiation and
chromosome number and to report its species identification and quality control.
To achieve optimal growth conditions, three different temperatures for incubation
including 18, 23 and 37 degrees C and two different media including DMEM and L
15 were applied. The expanded cells were studied for their potential to adipose
and osteoblast differentiation. Results indicated that lizard's original tail
cells could be successfully obtained by explant technique. The cells demonstrated
fibroblast like morphology with population doubling times of approximately 24 +/-
0.5 h. Karyotyping analysis showed a distribution of 2n = 40 chromosome number
for this cell line. The comparison of different incubation media and temperatures
showed that cell growth is equally optimal in all mentioned conditions according
to growth curves. Adipose and osteoblast differentiation was obviously observed
in these cells which confirms the hint of stem-ness in the produced mixed cells.
According to cell banking policies, produced cells were also checked for
bacterial, fungal, yeast and mycoplasma contaminations and no contamination was
observed. Multiplex PCR for identification of species confirmed the species of
lizard with no cross-contamination with other cells in the cell bank.
Establishment of authenticated and well-characterized lizard's original tail cell
line will provide a valuable source for subsequent in vitro regenerative research
and molecular studies which are not feasible in in vivo methods. This finding
will allow us to get an opportunity to create and preserve a new collection of
lizard cell lines in the future.
PMID- 29948550
TI - The Tumorgenicity of Glioblastoma Cell Line U87MG Decreased During Serial In
Vitro Passage.
AB - Established cancer cell lines are routinely used to study cancer. Several factors
such as serial passage may affect the reproducibility of experiments with cancer
cell lines, but few researches focused on these changes. In the present study,
different morphology and decreased tumorigenicity were observed in late passage
U87MG cells. In vitro experiments further revealed that late passage U87MG cells
possessed lower invasion properties than early passage, whereas no significant
differences of proliferation and migration were found between early and late
passage U87MG cells. In particular, we confirmed that late passage U87MG cells
exhibited more epithelial phenotype with decreased PI3K/Akt pathway and TGF-beta
pathway expressions at protein level. In summary, our results focused on the
changes of U87MG cells during serial in vitro passage, suggested that passage
induced changes may lead to notable changes of biological characteristics and
several molecular transitions in cancer cell lines, indicating the necessity to
shorten experiment-span and accomplish experiments with the same or similar
passage cancer cell strains.
PMID- 29948551
TI - Upregulation of miR-199a-5p Protects Spinal Cord Against Ischemia/Reperfusion
Induced Injury via Downregulation of ECE1 in Rat.
AB - Ischemia-reperfusion (I/R)-induced spinal cord injury can cause apoptotic damage
and subsequently act as a blood-spinal cord barrier damage. MicroRNAs (miRNAs)
contributed to the process of I/R injury by regulating their target mRNAs. miR
199a-5p is involved in brain and heart I/R injury; however, its function in the
spinal cord is not yet completely clarified. In this study, we investigated the
role of miR-199a-5p on spinal cord I/R via the endothelin-converting enzyme 1,
especially the apoptosis pathway. In the current study, the rat spinal cord I/R
injury model was established, and the Basso Beattie Bresnahan scoring, Evans blue
staining, HE staining, and TUNEL assay were used to assess the I/R-induced spinal
cord injury. The differentially expressed miRNAs were screened using microarray.
miR-199a-5p was selected by unsupervised hierarchical clustering analysis. The
dual-luciferase reporter assay was used for detecting the regulatory effects of
miR-199a-5p on ECE1. In addition, neuron expression was detected by
immunostaining assay, while the expressions of p-ERK, ERK, p-JNK, JNK, caspase-9,
Bcl-2, and ECE1 were evaluated by Western blot. The results indicated the
successful establishment of the I/R-induced spinal cord injury model; the I/R
induced the damage to the lower limb motor. Furthermore, 18 differentially
expressed miRNAs were detected in the I/R group compared to the sham group, and
miR-199a-5p protected the rat spinal cord injury after I/R. Moreover, miR-199a-5p
negatively regulated ECE1, and silencing the ECE1 gene also protected the rat
spinal cord injury after I/R. miR-199a-5p or silencing of ECE1 also regulated the
expressions of caspase-9, Bcl-2, p-JNK, p-ERK, and ECE1 in rat spinal cord injury
after I/R. Therefore, we demonstrated that miR-199a-5p might protect the spinal
cord against I/R-induced injury by negatively regulating the ECE1, which could
aid in developing new therapeutic strategies for I/R-induced spinal cord injury.
PMID- 29948552
TI - Dendritic Cells as an Alternate Approach for Treatment of Neurodegenerative
Disorders.
AB - Despite years of research, Alzheimer's disease (AD) remains incurable and thus
poses a major health challenge in coming years. This neurodegenerative disease
belongs to a heterogeneous group of human tauopathies, characterized by the
extracellular deposition of beta amyloid-Abeta and intracellular accumulation of
tau protein in neuronal and glial cells, whereby tau pathology best correlates
with disease progression. For decades, several disease-modifying agents were
brought to clinical studies with promising efficacy in preclinical trials;
however, all of the subsequent clinical trials failed. Therefore, the pursuit for
therapeutic agents for the treatment of AD and other tauopathies still continue.
Recent evidences show previously unidentified role of peripheral immune system in
regulating the inflammatory status of the brain, mainly the dendritic cells. A
decrease in functionality and count of dendritic cells has been observed in
Alzheimer's disease. Here, we discuss a potential role of dendritic cell-based
vaccines as therapeutic approach in ameliorating disease pathogenesis in AD and
other tauopathies.
PMID- 29948553
TI - The Hypothalamic-Pituitary-Adrenal Axis and Serotonin Metabolism in Individual
Brain Nuclei of Mice with Genetic Disruption of the NK1 Receptor Exposed to Acute
Stress.
AB - Mice lacking the substance P (SP) neurokinin-1 (NK1) receptor (NK1R-/-mice) were
used to investigate whether SP affects serotonin (5-HT) function in the brain and
to assess the effects of acute immobilisation stress on the hypothalamic
pituitary-adrenocortical (HPA) axis and 5-HT turnover in individual brain nuclei.
Basal HPA activity and the expression of hypothalamic corticotropin-releasing
hormone (CRH) in wild-type (WT)- and NK1R-/- mice were identical. Stress-induced
increases in plasma ACTH concentration were considerably higher in NK1R-/- mice
than in WT mice while corticosterone concentrations were equally elevated in both
mouse lines. Acute stress did not alter the expression of CRH. In the dorsal
raphe nucleus (DRN), basal 5-HT turnover was increased in NK1R-/- mice and a 15
min stress further magnified 5-HT utilisation in this region. In the
frontoparietal cortex, medial prefrontal cortex, central nucleus of amygdala, and
the hippocampal CA1 region, stress increased 5-HT and/or 5-hydroxyindoleacetic
acid (5-HIAA) concentrations to a similar extent in WT and NK1R-/- mice. 5-HT
turnover in the hypothalamic paraventricular nucleus was not affected by stress,
but stress induced similar increases in 5-HT and 5-HIAA in the ventromedial and
dorsomedial hypothalamic nuclei in WT and NK1R-/- mice. Our findings indicate
that NK1 receptor activation suppresses ACTH release during acute stress but does
not exert sustained inhibition of the HPA axis. Genetic deletion of the NK1
receptor accelerates 5-HT turnover in DRN under basal and stress conditions. No
differences between the responses of serotonergic system to acute stress in WT
and NK1R-/- mice occur in forebrain nuclei linked to the regulation of anxiety
and neuroendocrine stress responses.
PMID- 29948554
TI - R1 Resection for Colorectal Liver Metastases: a Survey Questioning Surgeons about
Its Incidence, Clinical Impact, and Management.
AB - BACKGROUND: A >= 1-mm margin is standard for resection of colorectal liver
metastases (CLM). However, R1 resection is not rare (10-30%), and chemotherapy
could mitigate its impact. The possibility of detaching CLM from vessels (R1
vascular margin) has been described. A reappraisal of R1 resection is needed.
METHODS: A 19-question survey regarding R1 resection for CLM was sent to
hepatobiliary surgeons worldwide. Seven clinical cases were included. RESULTS: In
total, 276 surgeons from 52 countries completed the survey. Ninety percent
reported a negative impact of R1 resection (74% local recurrence, 31% hepatic
recurrence, and 36% survival), but 50% considered it sometimes required for
resectability. Ninety-one percent of responders suggested that the impact of R1
resection is modulated by the response to chemotherapy and/or CLM
characteristics. Half considered the risk of R1 resection to be an indication for
preoperative chemotherapy in patients who otherwise underwent upfront resection,
and 40% modified the chemotherapy regimen when the tumor response did not
guarantee R0 resection. Nevertheless, 80% scheduled R1 resection for multiple
bilobar CLM that responded to chemotherapy. Forty-five percent considered the
vascular margin equivalent to R0 resection. However, for lesions in contact with
the right hepatic vein, right hepatectomy remained the standard. Detachment from
the vein was rarely considered (10%), but 27% considered detachment in the
presence of multiple bilobar CLM. CONCLUSIONS: A negative margin is still
standard for CLM, but R1 resection is no longer just a technical error. R1
resection should be part of the modern multidisciplinary, aggressive approach to
CLM.
PMID- 29948555
TI - Quantum-like behavior without quantum physics II. A quantum-like model of neural
network dynamics.
AB - In earlier work, we laid out the foundation for explaining the quantum-like
behavior of neural systems in the basic kinematic case of clusters of neuron-like
units. Here we extend this approach to networks and begin developing a dynamical
theory for them. Our approach provides a novel mathematical foundation for neural
dynamics and computation which abstracts away from lower-level biophysical
details in favor of information-processing features of neural activity. The
theory makes predictions concerning such pathologies as schizophrenia, dementias,
and epilepsy, for which some evidence has accrued. It also suggests a model of
memory retrieval mechanisms. As further proof of principle, we analyze certain
energy-like eigenstates of the 13 three-neuron motif classes according to our
theory and argue that their quantum-like superpositional nature has a bearing on
their observed structural integrity.
PMID- 29948556
TI - Potential of Fecal Calprotectin as an Objective Marker to Discriminate
Hospitalized Patients with Acute Severe Colitis from Outpatients with Less Severe
Disease.
AB - BACKGROUND: Acute severe colitis (ASC) is conventionally diagnosed by Truelove
and Witts' criteria which are non-specific and can be affected by other
pathologic conditions. Fecal calprotectin (FCP) is a gut-specific marker of
inflammation which can predict short-term outcomes in patients with ASC. We aimed
to define the role of FCP in the diagnosis of ASC. METHODS: This prospective
observational cohort study included adult patients (> 18 years) with ulcerative
colitis (UC) for whom FCP was measured and was under follow-up from April 2015 to
December 2016. Patients were divided into two cohorts: (1) all consecutive
hospitalized patients with ASC as defined by Truelove and Witts' criteria; (2)
outpatients with active UC (defined by Mayo score) who did not fulfill Truelove
and Witts' criteria. FCP levels were compared between the two cohorts, and a
cutoff for FCP to diagnose ASC was determined. RESULTS: Of 97 patients, 49 were
diagnosed with ASC (mean age: 36.1 +/- 11.9 years, 36 males) and 48 with active
UC (mean age: 37.9 +/- 12.4 years, 25 males). Median FCP levels were
significantly higher in patients with ASC [1776(952-3123) vs 282(43-568) ug/g, p
< 0.001] than mild to moderately active UC (n = 48) or moderately active UC [n =
35, 1776(952-3123) vs 332(106-700) ug/g, p < 0.001]. A FCP cutoff of 782 MUg/g of
stool had excellent diagnostic accuracy, with an area under the curve of 0.92(95%
CI 0.87-0.97), sensitivity of 84% and specificity of 88% to differentiate ASC
from active UC. CONCLUSION: FCP could differentiate ASC from mild to moderate
patients with UC, but requires validation before clinical use.
PMID- 29948557
TI - Origins of Metaplasia in the Esophagus: Is This a GE Junction Stem Cell Disease?
AB - The incidence of esophageal adenocarcinoma (EAC) and its precursor lesion
Barrett's esophagus (BE) has been increasing steadily in the western world in
recent decades. Understanding the cellular origins of BE and the conditions
responsible for their malignant transformation would greatly facilitate risk
assessment and identification of patients at risk of progression, but this topic
remains a source of debate. Here, we review recent findings that have provided
support for the gastroesophageal junction (GEJ) as the main source of stem cells
that give rise to BE and EAC. These include both gastric cardia cells and
transitional basal cells. Furthermore, we discuss the role of chronic injury and
inflammation in a tumor microenvironment as a major factor in promoting stem cell
expansion and proliferation as well as transformation of the GEJ-derived stem
cells and progression to EAC. We conclude that there exists a large amount of
empirical support for the GEJ as the likely source of BE stem cells. While BE
seems to resemble a successful adaptation to esophageal damage, carcinogenesis
appears as a consequence of natural selection at the level of GEJ stem cells, and
later glands, that expand into the esophagus wherein the local ecology creates
the selective landscape for cancer progression.
PMID- 29948558
TI - Negative Regulation of Kruppel-Like Factor 4 on microRNA-106a at Upstream
Transcriptional Level and the Role in Gastric Cancer Metastasis.
AB - BACKGROUND: MicroRNAs are classes of endogenous noncoding RNAs that play a
substantial role in tumor processes through regulating the targets at
posttranscriptional level. However, little is known about the upstream
transcription regulatory mechanism although it is a prerequisite for
investigation of its aberrant expression and function. AIMS: This report
evaluates miR-106a's direct transcriptional factor from upstream level to in
depth elucidate their communication in gastric cancer development. METHODS:
Gastric cancer tissues were collected to analyze the miR-106a expression using
real-time PCR methods. The combination of Kruppel (or Kruppel)-like factor 4
(KLF4) to miR-106a promoter was testified through bioinformatics followed by
construction of luciferase reporter plasmid and chromatin immunoprecipitation
assay. Functional experiments and mouse models for evaluating cell growth and
metastasis were conducted to observe the biological effect of KLF4 on miR-106a.
The interplay between KLF4 and miR-106a was tested with Wnt activator and
confirmed in clinical specimens. RESULTS: The up-regulated miR-106a linked to
gastric cancer metastasis and epithelial-mesenchymal transition. UCSC and JASPAR
predicted the promoter sequence of miR-106a and its binding site with
transcriptional factor KLF4. Construction of reporter gene further verified their
direct combination at upstream level. Moreover, the inhibitory effect of KLF4 on
the phenotype of gastric cancer cells could be restored by miR-106a. CHIR-induced
experiment and clinical specimens confirmed the negative regulation of KLF4 on
miR-106a. CONCLUSIONS: Our findings provide novel direct insights into molecular
mechanisms for interaction of KLF4 and miR-106a at upstream level and new ways
for clinical application of KLF4-miR-106a axis in advanced gastric cancer
metastasis.
PMID- 29948560
TI - A Goblet (Cell) Half Full: What Do We Really Know About Barrett's Esophagus-A
Tribute to Emmet Keeffe.
PMID- 29948561
TI - Managing PBC: Expanding the Provider Comfort Zone.
PMID- 29948559
TI - Epstein-Barr Virus Antibody Titers Are Not Associated with Gastric Cancer Risk in
East Asia.
AB - BACKGROUND: Epstein-Barr virus (EBV)-positive gastric cancers represent a
distinct subtype of gastric cancers and account for nearly 10% of the gastric
cancer burden, yet risk detection strategies for this cancer subtype are lacking.
METHODS: We conducted a nested case-control study where we assayed 4 EBV antigens
[viral capsid antigen (VCA), early antigen (EA), Epstein-Barr nuclear antigen
(EBNA), and BZLF1-encoded replication activator protein (ZEBRA)] in either sera
or plasma from 1447 gastric cancer cases and 1797 controls obtained from seven
prospective cohorts representing individuals from the high gastric cancer-risk
countries of China, Japan, and Korea. RESULTS: The prevalence of EBV sero
positivity was universal with the exception of one sero-negative individual, and
the highest titers of the EBV antigens VCA (OR 0.95, 95% CI 0.78-1.17), EBNA (OR
0.88, 95% CI 0.72-1.08), EA (OR 0.97, 95% CI 0.79-1.19), and ZEBRA (OR 0.87, 95%
CI 0.71-1.07) were not associated with risk of incident gastric cancer. When we
stratified these data by H. pylori status, there was no change in the
association. CONCLUSIONS: Multiplex serology of the aforementioned EBV antigens
in serum may not be a suitable biomarker for predicting gastric cancer risk in
East Asian populations.
PMID- 29948562
TI - Comparison of Point-of-Care and Classical Immunoassays for the Monitoring
Infliximab and Antibodies Against Infliximab in IBD.
AB - OBJECTIVE: The primary objective is to assess whether the POC assays to measure
infliximab residual trough level in the serum of IBD patients were non-inferior
to the ELISA techniques available on the market, and to determine which of them
was the most robust. The second is to compare three different ELISA kits for
monitoring anti-infliximab antibodies (ATI). METHODS: The assays were carried out
on patients' sera using four ELISA kits from four different suppliers (three with
a monoclonal antibody and one polyclonal) and two rapid techniques provided by
BUHLMANN (Quantum Blue(r)) and R-Biopharm (Ridaquick) for monitoring infliximab
levels. ATI were measured by three ELISA sets (Grifols, Theradiag, and R
Biopharm) which have different positivity limits and different units. RESULTS: We
measured infliximab residual level and ATI in the serum of 90 IBD patients (85
treated with infliximab and five with adalimumab). All of the infliximab assays
were very well correlated when analyzed with Spearman nonparametric correlation
(0.93 <= r <= 0.99), and the two POC assays were also excellently correlated (r =
0.98). The ATI monitoring kits revealed a correlation ranging from 0.73 to 0.96
when comparing positive and negative patients. When normalizing the quantitative
values between the different ELISA tests (expressed arbitrarily by using
multiples of the positivity limits defined by each supplier), the Spearman r
coefficient ranged from 0.81 to 0.93. CONCLUSION: The available evidence allows
us to conclude that all of the infliximab monitoring assays correlate well and
may be used for IFX monitoring; albeit variations in measured IFX concentration
among different assays remain present, these assays could be interchangeable. The
ATI monitoring techniques are all capable of detecting ATI-positive patients, but
because of the difference in the positivity limits and the measurement units, it
is better to follow a patient rate with one definite kit.
PMID- 29948564
TI - Cecal Insertion Time and the ADR: Patience Is Good for Patients.
PMID- 29948565
TI - Management of Radiation Proctitis.
AB - Radiation proctitis is radiation-induced rectal mucositis, occurring as a result
of radiation therapy for various pelvic malignancies. The management of radiation
proctitis is challenging as guidelines are not currently available, and studies
of the various treatment modalities are limited. There are various medical,
endoscopic, and surgical measures for treating chronic radiation proctitis.
Medical options such as anti-inflammatory agents, antioxidants, formalin
application, and hyperbaric oxygen may improve bleeding related to chronic
radiation proctitis. Endoscopic measures such as argon plasma coagulation are
effective and safe. Surgery is considered for refractory or severe cases. A
review and discussion of the different treatment modalities is presented.
PMID- 29948566
TI - Chemoprevention of Barrett's Esophagus and Esophageal Adenocarcinoma.
AB - Barrett's esophagus is common in Western countries, but progression to esophageal
adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether
benefits outweigh risks given an otherwise healthy population. This will depend
on the particular population at risk and the relative safety of a potential
preventive agent. Most evidence regarding the potential benefit of
chemoprevention of Barrett's esophagus and prevention of progression to
esophageal adenocarcinoma is based on observational studies such as case-control
and cohort studies. Given the potential benefits and relatively low risks,
patients with BE should receive once-daily PPI therapy, but routine use of twice
daily PPI is not recommended unless necessitated by poor control of reflux
symptoms or esophagitis. Recent data suggest that the inverse associations
between aspirin/NSAID use and esophageal adenocarcinoma may be the result of
reducing neoplastic progression (from metaplasia to dysplasia and carcinoma)
rather than initiation of Barrett's esophagus. While substantial associative data
suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk
of progression of Barrett's esophagus, the low risk of progression and the
potential risks (gastrointestinal bleeding, complicated ulcer disease,
hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular
risk. Chemoprevention after mucosal ablation in those at highest risk of post
ablation recurrence (dysplastic Barrett's) is currently under investigation.
PMID- 29948567
TI - Epinephrine Dose Has a Preventive Effect on the Occurrence of Stress Ulcer
Induced Gastrointestinal Bleeding in Critically Ill Patients.
AB - BACKGROUND: Epinephrine may impair splanchnic blood flow, but the impact of
epinephrine dose on the occurrence of clinically significant gastrointestinal
bleeding (CSGB) caused by stress ulcer remains unclear. We investigated the
effect of epinephrine dose on the occurrence of stress ulcer-related CSGB in
intensive care unit (ICU) patients. METHODS: In this prospective, observational,
cohort study conducted in a French teaching hospital, 40 consecutive ICU patients
receiving epinephrine infusion in whom a stress ulcer was diagnosed by an upper
gastrointestinal endoscopy were included, from February 2010 to July 2015. The
effects of epinephrine dose, and other covariates, on the occurrence of stress
ulcer-related CSGB were analyzed using a multiple logistic regression model for
repeated measures: At each observation, each patient serves as his own control.
RESULTS: A total of 1484 time-dependent epinephrine dose modifications were
available for analysis. The median epinephrine dose rate was 0.8 (0-9.5) mg/h,
and the median epinephrine cumulative dose was 44.8 (2.6-2343) mg. Epinephrine,
expressed as the average dose per day at time t, had a significant protective
effect on the occurrence of stress ulcer (odds ratio 0.22; 95% confidence
interval (CI), 0.12-0.38; p < 0.0001, for a log10 increase of epinephrine dose).
Enteral feeding had also a protective effect (odds ratio 0.55; 95% CI 0.41-0.72;
p < 0.0001, for a log10 increase of kcal/day). Only renal replacement therapy
increased the occurrence of stress ulcer in the model. CONCLUSIONS: An increase
in the average dose of epinephrine per day increased the time to occurrence of
stress ulcer in critically ill patients.
PMID- 29948563
TI - Are Gastric and Esophageal Metaplasia Relatives? The Case for Barrett's Stemming
from SPEM.
AB - Chronic injury and inflammation in the esophagus can cause a change in cellular
differentiation known as metaplasia. Most commonly, the differentiation changes
manifest as Barrett's esophagus (BE), characterized by the normal stratified
squamous epithelium converting into a cuboidal-columnar, glandular morphology. BE
cells can phenotypically resemble specific normal cell types of the stomach or
intestine, or they can have overlapping phenotypes in disorganized admixtures.
The stomach can also undergo metaplasia characterized by aberrant gastric or
intestinal differentiation patterns. In both organs, it has been argued that
metaplasia may represent a recapitulation of the embryonic or juvenile
gastrointestinal tract, as cells access a developmental progenitor genetic
program that can help repair damaged tissue. Here, we review the normal
development of esophagus and stomach, and describe how BE represents an
intermixing of cells resembling gastric pseudopyloric (SPEM) and intestinal
metaplasia. We discuss a cellular process recently termed "paligenosis" that
governs how mature, differentiated cells can revert to a proliferating progenitor
state in metaplasia. We discuss the "Cyclical Hit" theory in which paligenosis
might be involved in the increased risk of metaplasia for progression to cancer.
However, somatic mutations might occur in proliferative phases and then be
warehoused upon redifferentiation. Through years of chronic injury and many
rounds of paligenosis and dedifferentiation, eventually a cell with a mutation
that prevents dedifferentiation may arise and clonally expand fueling stable
metaplasia and potentially thereafter acquiring additional mutations and
progressing to dysplasia and cancer.
PMID- 29948568
TI - Effect of Metabolic Syndrome on the Clinical Outcomes of Chronic Hepatitis B
Patients with Nucleos(t)ide Analogues Treatment.
AB - BACKGROUND: No data are available about the effect of MS on oral nucleos(t)ide
analogues (NUCs) treatment and clinical outcomes in chronic hepatitis B (CHB)
patients. AIMS: We aimed to elucidate whether coexistence of MS and CHB affects
the long-term prognosis of CHB patients with oral NUCs treatment. METHODS: We
performed a retrospective data analysis for a total of 587 CHB patients who
started oral NUCs treatment for the first time in our institution from January
2006 to March 2016. RESULTS: Among the 587 patients, 70 (11.9%) had MS, but 517
(88.1%) had no evidence of MS when oral NUCs treatment was initiated. Cumulative
occurrence rates of viral breakthrough, genotypic resistance, HCC, disease
progression (PD), and overall adverse outcomes (OAO) were significantly higher in
CHB patients with MS than in those without MS, although HBV-DNA suppression and
cumulative occurrence rates of HBeAg negative conversion and seroconversion were
not significantly different between the two groups. The overall survival (OS) was
also significantly shorter in CHB patients with MS than in those without MS.
Multivariate analysis indicated that the MS was an independent, poor prognostic
factor for occurrence of genotypic resistance (adjusted hazard ratio [aHR], 22.3;
95% confidence interval [CI] 6.61-75.02; P < 0.001), HCC (aHR, 3.98; 95% CI 2.07
7.66; P < 0.001), PD (aHR, 6.18; 95% CI 3.43-11.14; P < 0.001), OAO (aHR, 8.10;
95% CI 4.68-14.02; P < 0.001), and OS (aHR, 12.29; 95% CI 2.25-67.24; P < 0.001).
CONCLUSIONS: MS is an independent determinant of poor prognosis in CHB patients
receiving oral NUCs treatment.
PMID- 29948569
TI - Cost-Effectiveness of Melanoma Screening in Inflammatory Bowel Disease.
AB - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) patients are at increased
risk of melanoma and non-melanoma skin cancers, and preventive care guidelines in
IBD favor annual skin examinations. Here we estimate the cost-effectiveness of
annual melanoma screening in IBD. METHODS: Melanoma screening was defined as
receiving annual total body skin examinations starting at age 40 from a
dermatologist. Screening was compared to US background total body skin
examination rates performed by primary care practitioners. A Markov model was
used to estimate intervention costs and effectiveness. Future costs and
effectiveness were discounted at 3% per year over a lifetime horizon. Strategies
were compared using a willingness-to-pay threshold of $100,000/quality-adjusted
life year (QALY) gained. RESULTS: Annual melanoma screening cost an average of
$1961 per patient, while no screening cost $81 per patient. Melanoma screening
was more effective, gaining 9.2 QALYs per 1000 persons, at a cost of
$203,400/QALY gained. Screening every other year was the preferred strategy,
gaining 6.2 QALYs per 1000 persons and costing $143,959/QALY. One-way sensitivity
analyses suggested the relative risk of melanoma in IBD, melanoma progression,
and screening costs were most influential with clinically plausible variation,
leading to scenarios costing < $100,000/QALY gained. Probabilistic sensitivity
analyses suggested screening every other year was cost-effective in 17.4% of
iterations. CONCLUSIONS: Screening for melanoma in IBD patients was effective but
expensive. Screening every other year was the most cost-effective strategy.
Studies to identify IBD patients at the highest risk of developing melanoma may
assist in targeting a prevention program in the most cost-effective manner.
PMID- 29948572
TI - Thyroid diseases and skin autoimmunity.
AB - The skin is the largest organ of the body, at the boundary with the outside
environment. Primarily, it provides a physical and chemical barrier against
external insults, but it can act also as immune organ because it contains a whole
host of immune-competent cells of both the innate and the adaptive immune
systems, which cooperate in eliminating invading pathogens following tissue
injury. On the other hand, improper skin immune responses lead to autoimmune skin
diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia.
Although the interplay among genetic, epigenetic, and environmental factors has
been shown to play a major role in AISD etiology and progression, the molecular
mechanisms underlying disease development are far from being fully elucidated. In
this context, epidemiological studies aimed at defining the association of
different AISD with other autoimmune pathologies revealed possible shared
molecular mechanism(s) responsible for disease progression. In particular, over
the last decades, a number of reports have highlighted a significant association
between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we
will recapitulate the epidemiology, clinical manifestations, and pathogenesis of
the main AISD, and we will summarize the epidemiological evidence showing the
associations with TD as well as possible molecular mechanism(s) underlying TD and
AISD pathological manifestations.
PMID- 29948571
TI - Screening and Surveillance for Barrett's Esophagus: Is It Cost-Effective?
AB - The cost-effectiveness of screening and surveillance for Barrett's esophagus
continues to evolve as the incidence of esophageal adenocarcinoma increases,
biomarkers enhance the identification of individuals at highest risk for
developing cancer, and endoscopic eradication of Barrett's esophagus improves.
Screening to detect Barrett's esophagus may be cost-effective in selected high
risk groups based on age, race, sex and other factors such as symptoms of
heartburn. Currently, endoscopic eradication therapy for Barrett's esophagus and
high-grade dysplasia is a cost-effective intervention, while endoscopic therapy
for non-dysplastic Barrett's esophagus is not a cost-effective strategy. As
diagnosis of low-grade dysplasia improves, endoscopic eradication therapy may
also prove to be a cost-effective intervention.
PMID- 29948570
TI - Screening Women Aged 50-59 for CRC Using Fecal Occult Blood Test Produces
Outcomes Similar to Men Undergoing Screening Colonoscopy.
AB - BACKGROUND: Average-risk women aged 50-59 years have a lower incidence and
mortality of colorectal cancer relative to age-matched men, calling into question
the benefit of screening colonoscopy in this age group. AIMS: We aimed to
determine whether FOBT is an effective initial screening test in 50-59-year-old
women. METHODS: We conducted a cross-sectional study using a computerized
endoscopic report generator. We identified 320,906 individuals who had average
risk screening colonoscopy and 32,369 who had colonoscopy for positive FOBT. The
primary outcome was the positive predictive value (PPV) of FOBT for large
polyp(s) greater than 9 mm, as a surrogate for advanced neoplasia. RESULTS: Among
patients aged 50-59 years undergoing screening colonoscopy, men were more likely
than women to have large polyps (6.3 vs 4.2%, p < 0.0001). Black women undergoing
screening colonoscopy had higher rates of large polyps compared to non-Black
women. The PPV in FOBT-positive men aged 50-54 (11.5%) and 55-59 (14.4%) was
higher than in women aged 50-54 (6.1%) and 55-59 (5.4%). Despite this lower PPV,
women aged 50-54 with a positive FOBT had a similar rate of large polyps as 50-54
year-old men undergoing screening colonoscopy (6.1 vs 6.3%, p = 0.626).
CONCLUSIONS: CRC screening with FOBT identifies 50-59-year-old men and women with
a higher risk of large polyps. Since younger women have a lower risk of large
polyps than men, screening with FOBT in 50-59-year-old non-Black women could be
an effective screening strategy, with outcomes similar to the use of screening
colonoscopy in 50-59-year-old men.
PMID- 29948573
TI - Survey Response Rate and Quality in a Mental Health Clinic Population: Results
from a Randomized Survey Comparison.
AB - Given the limited ability of informatics-based assessment technologies to reach
individuals with serious mental health conditions, this study evaluated the
feasibility and data quality of mail-out healthcare surveys in this population to
assist in measure selection for a multi-site controlled implementation trial.
Veterans were randomly selected from those who had received services at a mental
health clinic in the Department of Veterans Affairs, and were randomly assigned
to one of three questionnaire lengths. Survey length (48-127 items) was not
associated with differences in response rate, percent of items missing, or data
quality. However, internal consistency reliability was variable among scales and
survey lengths. Additional analyses indicate the above measures of survey data
quality may differ among respondents who are non-white and younger and have
psychotic disorders. These results can inform survey protocols to ensure maximal
representation of this vulnerable population in health planning and policy
assessment.
PMID- 29948574
TI - T+ NK+ IL-2 Receptor gamma Chain Mutation: a Challenging Diagnosis of Atypical
Severe Combined Immunodeficiency.
AB - PURPOSE: All reported patients with hypomorphic X-linked severe combined
immunodeficiency (X-SCID) due to c.664C>T (p.R222C) mutations in the gene (IL2RG)
encoding the common gamma chain (gammac) have presented with opportunistic
infections within the first year of life, despite the presence of nearly normal
NK and T cell numbers. Reporting five children of one extended family with
hemizygous mutations in IL2RG, we explore potential diagnostic clues and extend
our comprehension of the functional impact of this mutation. METHODS: Whole exome
sequencing (WES); detailed immune phenotyping; cytokine-induced STAT
phosphorylation; B, T, and NK cell activation; and quantification of sjTRECs in
five Arab children with c.664C>T (p.R222C) IL2RG mutation. RESULTS: The mean age
at clinical presentation with respiratory tract infection or diarrhea was 6.8
(range: 2-12) months. None of the children presented with opportunistic
infections. Diagnostic clues were early onset in the first year of life, and a
suggestive family history associated with reduced naive CD4 T cells and absent
switched memory B cells. Number and phenotype of NK cells and innate-like
lymphocytes were normal. The diagnosis was made by WES and corroborated by absent
STAT phosphorylation and reduced functional response after IL-2 and IL-21
stimulation. Four patients underwent successful hematopoietic stem cell
transplantation. CONCLUSIONS: As early diagnosis and treatment are important, a
high index of suspicion in the diagnosis of c.664C>T (p.R222C) X-SCID is needed.
This requires prompt genetic testing by next generation sequencing in order to
avoid unnecessary delays in the definite diagnosis since immunological work up
may not be discriminating. Assays directly testing cytokine signaling or cytokine
dependent functions are helpful in confirming the functional impact of the
identified hypomorphic variants.
PMID- 29948575
TI - Clearing Vaccine-Derived Poliovirus Infection Following Hematopoietic Stem Cell
Transplantation: a Case Report and Review of Literature.
AB - The use of oral poliovirus vaccine in a worldwide scale has led to a 99.9%
decrease in annual incidence of wild-type poliomyelitis and the eradication of
serotype 2 poliovirus. However, the emergence of vaccine-derived polioviruses
(VDPVs) is endangering the eradication program. Patients with combined
immunodeficiencies are at increased risk of both vaccine-associated poliomyelitis
and prolonged asymptomatic infection with immunodeficiency-associated VDPVs
(iVDPVs). Herein, we present a severe combined immunodeficiency patient with
prolonged and asymptomatic iVDPV infection. He continued to shed poliovirus
during immunoglobulin replacement therapy and cleared the infection following
successful hematopoietic stem cell transplantation (HSCT). To explain the
efficiency of HSCT in clearing the infection, we reviewed the literature for all
reports of HSCT in iVDPV-excreting patients and discussed novel ideas about the
role of different immune mechanisms, including cell-mediated interactions, in
mounting immune responses against poliovirus infections. This study could provide
further insights into the immune mechanisms contributing to the clearance of
enteroviral infections.
PMID- 29948576
TI - IKBA S32 Mutations Underlie Ectodermal Dysplasia with Immunodeficiency and Severe
Noninfectious Systemic Inflammation.
PMID- 29948578
TI - Cancer-associated fibroblasts enhance cell proliferation and metastasis of
colorectal cancer SW480 cells by provoking long noncoding RNA UCA1.
AB - Cancer-associated fibroblasts (CAFs) have been considered as major players in
tumor growth and malignancy. In colorectal cancer (CRC), CAFs are attendance in
high affluence and little is known about how they impact tumor progression. An
increasing number of studies indicated that dysregulation of human urothelial
carcinoma associated 1 (UCA1) is associated with progression of tumor and
metastasis in various cancers including CRC. Nonetheless, the possible mechanisms
of UCA1 actuation in CRC remain poorly understood. To address this, we elucidated
the effects of conditioned medium from SW480 CRC cells/Normal fibroblast co
culture (CAF-CM) on UCA1 expression, and the cell proliferation, EMT, invasion
and migration of the treated CRC cell were evaluated in vitro. Our study
indicated that CAFs dramatically stimulated cell proliferation and migration of
CRC cell. Furthermore, CAFs induced the EMT phenotype in CRC cell, with an
associated change in the expression of EMT markers including vimentin, E
cadherin, N-cadherin and metastasis-related genes (MMPs). Moreover, we found an
increased percentage of CRC cell in the S and G2/M phase induced by CAFs. Our
results revealed that CAFs could induce upregulation of UCA1, leading to
upregulation of mTOR. Up-regulation of UCA1/mTOR axis suppressed p27 and miR-143
while the expression of Cyclin-D1 and KRAS were significantly increased compared
with control. Furthermore, UCA1 silencing in treated CRC cell suggested that
upregulation of UCA1, which was induced by CAFs, regulates the expression of
downstream key effectors. Taken together, these results highlight the vital role
of cooperation between lncRNA UCA1 and mTOR in proliferation and metastasis which
support the hypothesis that CAFs may be a prominent therapeutic target of stroma
based therapy in CRC treatment.
PMID- 29948577
TI - Increased Ap4A levels and ecto-nucleotidase activity in glaucomatous mice retina.
AB - The pathogenesis of glaucoma involves numerous intracellular mechanisms including
the purinergic system contribution. Furthermore, the presence and release of
nucleotides and dinucleotides during the glaucomatous damage and the maintenance
of degradation machinery through ecto-nucleotidase activity are participating in
the modulation of the suitable extracellular complex balance. The aim of this
study was to investigate the levels of diadenosine tetraphosphate (Ap4A) and the
pattern of ecto-nucleotidase activity expression in glaucomatous retinas during
the progress the pathology. Ap4A levels were analyzed by HPLC in glaucomatous
retinas from the DBA/2J mice at 3, 9, 15, and 23 months of age. For that, retinas
were dissected as flattened whole-mounts and stimulated in Ringer buffer with or
without 59 mM KCl. NPP1 expression was analyzed by RT-PCR and western blot and
its distribution was assessed by immunohistochemistry studies examined under
confocal microscopy. Glaucomatous mice exhibited Ap4A values, which changed in
stimulated retinas as long as the pathology progressed varying from 0.73 +/- 0.04
(3 months) to 0.170 +/- 0.05 pmol/mg retina (23 months). Concomitantly, NPP1
expression was significantly increased (82.15%) in the DBA/2J mice at 15 months.
Furthermore, immunohistochemical studies showed that NPP1 labeling was stronger
in OPL and IPL labeling tangentially in the vitreal part of the retina and was
upregulated at 15 months of age. Our findings demonstrate that Ap4A decreased
levels may be related with exacerbated activity of NPP1 protein in glaucomatous
degeneration and in this way contributing to elucidate different mechanisms
involved in retinal impairment in glaucomatous degeneration.
PMID- 29948579
TI - New approaches for censored longitudinal data in joint modelling of longitudinal
and survival data, with application to HIV vaccine studies.
AB - In HIV vaccine studies, longitudinal immune response biomarker data are often
left-censored due to lower limits of quantification of the employed immunological
assays. The censoring information is important for predicting HIV infection, the
failure event of interest. We propose two approaches to addressing left censoring
in longitudinal data: one that makes no distributional assumptions for the
censored data-treating left censored values as a "point mass" subgroup-and the
other makes a distributional assumption for a subset of the censored data but not
for the remaining subset. We develop these two approaches to handling censoring
for joint modelling of longitudinal and survival data via a Cox proportional
hazards model fit by h-likelihood. We evaluate the new methods via simulation and
analyze an HIV vaccine trial data set, finding that longitudinal characteristics
of the immune response biomarkers are highly associated with the risk of HIV
infection.
PMID- 29948580
TI - Synthesis, docking and anticancer activity of azo-linked hybrids of 1,3,4-thia
/oxadiazoles with cyclic imides.
AB - A series of novel analogues based on a diazole-imide pharmacophore were
synthesized by diazotizing substituted 1,3,4-thia-/oxadiazol-2-amines and
subsequently coupling the resulting diazonium salts with N-substituted cyclic
imides. The resulting compounds C1 to C28 were characterized by various spectral
methods, viz. IR, NMR and mass spectroscopy. All the synthesized compounds were
tested against two human cancer cell lines: human breast adenocarcinoma cell line
MCF-7 and colorectal adenocarcinoma cell line HT-29. Among the synthesized
compounds, C14 (2-(4-chloro-3-((5-(4-nitrophenyl)-1,3,4-thiadiazol-2
yl)diazenyl)phenyl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione) emerged as a
potential candidate against both MCF-7 and HT-29 with [Formula: see text] values
of 0.09 +/- 0.02 [Formula: see text]M and 0.11 +/- 0.03 [Formula: see text]M,
respectively. Similarly, compound C16 displayed highest anticancer activity
against MCF-7 cell line with [Formula: see text] = 0.07 +/- 0.02 [Formula: see
text]M. Target fishing (inverse docking) using ChemMapper server identified EGFR
tyrosine and CDK2 kinases as high priority targets for this pharmacophore.
Computational docking (AutoDock 4.2) was used to analyse the interactions between
the target proteins and active compounds.
PMID- 29948581
TI - Synthesis, in vitro [Formula: see text]-glucosidase inhibitory activity, and in
silico study of (E)-thiosemicarbazones and (E)-2-(2-(arylmethylene)hydrazinyl)-4
arylthiazole derivatives.
AB - This study is focused on the identification of thiazole-based inhibitors for the
[Formula: see text]-glucosidase enzyme. For that purpose, (E)-2-(2
(arylmethylene)hydrazinyl)-4-arylthiazole derivatives were synthesized in two
steps and characterized by various spectroscopic techniques. All derivatives and
intermediates were evaluated for their in vitro [Formula: see text]-glucosidase
inhibitory activity. Thiosemicarbazones 20 and 35, and cyclized thiazole
derivatives 2, 5-11, 13, 15, 21-24, 27-31, and 36-37 showed significant
inhibitory potential in the range of [Formula: see text]-[Formula: see text] as
compared to standard acarbose ([Formula: see text]). A molecular modeling study
was carried out to understand the binding interactions of compounds with the
active site of enzyme.
PMID- 29948582
TI - Highly efficient synthesis of alkyl and aryl primary thiocarbamates and
dithiocarbamates under metal- and solvent-free conditions.
AB - A highly efficient, metal-free and solvent-free process is reported for the
preparation of novel series of alkyl and aryl primary thiocarbamates and
dithiocarbamates through the reaction of aliphatic alcohols, phenols and thiols
with thiocyanate salts in the presence of 4-dodecylbenzenesulfonic acid (DBSA) as
an inexpensive, readily available and amphipathic acid reagent. All reactions
proceeded smoothly, and the products are obtained in good to excellent yields.
Using this method, a wide range of structurally diverse primary thiocarbamates
was prepared successfully.
PMID- 29948584
TI - Long-term outcomes after "Zero X-ray" arrhythmia ablation.
AB - PURPOSE: Radiation exposure related to conventional tachyarrhythmia
radiofrequency catheter ablation (RFCA) carries small but definite risk for both
patients and operators. Today, non-fluoroscopic mapping systems enable to perform
catheter ablation with minimal or zero fluoroscopy. The purpose of this study was
to evaluate the long-term outcome of patients who had undergone "Zero X-ray"
ablation, since no information is available on the very long-term benefits.
METHODS: A total of 272 arrhythmias in 266 patients have been treated with
catheter ablation by means of a zero-ray approach guided only by a
nonconventional mapping system (EnSite NavXTM, EnsiteTM VelocityTM mapping
system; subsequently EnsiteTM PrecisionTM Abbott, St. Paul, MN). Fluoroscopy was
never used. RESULTS: Over a period of 6 years, patients were followed up for an
average of 2.9 +/- 1.6 years. A 100% rate of acute success was observed in the
study population, with a complication rate of 0.8%. Chronic success was achieved
in 90.8% of the total number of procedures (272). Patients in whom the same
arrhythmia recurred during follow-up underwent to a redo catheter ablation
procedure in 60.0% of cases, while the remaining 40.0% underwent pharmacological
treatment. A new post-ablation arrhythmia occurred in 7.7% of the sample.
CONCLUSIONS: The non-fluoroscopic approach is a feasible and safe alternative to
fluoroscopy for arrhythmias ablation. This method ensures low complications
rates, high acute procedural success rates, and comparable long-term outcomes
with clinical benefits for both patients and physicians. The complete elimination
of fluoroscopy during catheter ablation is advantageous and does not reduce
patient safety.
PMID- 29948583
TI - Electrocardiographic characteristics for predicting idiopathic right ventricular
outflow tract premature ventricular complex-induced cardiomyopathy.
AB - PURPOSE: In spite of several proposed predictors for premature ventricular
complex (PVC)-induced cardiomyopathy (PVC-CMP), the specific ECG features of
idiopathic right ventricular outflow tract (RVOT) PVC-CMP remain unknown.
METHODS: A total of 130 patients (49 males, mean age 44 years) with symptomatic
and drug-refractory idiopathic RVOT PVCs undergoing radiofrequency catheter
ablation (RFCA) were enrolled. The patients were categorized into two groups,
including those with and without RVOT PVC-CMP (left ventricular ejection fraction
(LVEF) < 50%, n = 25 and LVEF >= 50%, n = 105, respectively). The 12-lead PVC
morphologies were assessed. RESULTS: Patients with RVOT PVC-CMP had a lower LVEF
(42 +/- 5% vs. 60 +/- 7%, P < 0.01) and higher PVC burden (24 +/- 14% vs. 15 +/-
11%, P = 0.02) when compared to patients without RVOT PVC-CMP. The PVC features
in those with PVC-CMP displayed a significantly wider QRS duration (143 +/- 14 ms
vs. 132 +/- 17 ms, P < 0.01) and higher peak deflection index (PDI; 0.60 +/- 0.07
vs. 0.55 +/- 0.08, P < 0.01). A multivariate analysis demonstrated that the QRS
duration (odds ratio (OR) 1.130, 95% confidence interval (CI) 1.020-1.253, P =
0.02) and PDI (OR 1.240, 95% CI 1.004-1.532, P = 0.04) were independently
associated with RVOT PVC-CMP. Based on the receiver-operating characteristic
analysis, a QRS duration > 139 ms and PDI > 0.57 could predict RVOT PVC-CMP (area
under the curve (AUC) 0.710 and AUC 0.690, respectively). The elimination and
suppression of PVCs by RFCA resulted in the recovery of the LVEF in RVOT PVC-CMP.
CONCLUSIONS: The ECG parameters, including a wider QRS duration and higher PDI,
could predict the development of RVOT PVC-CMP, which could be effectively treated
by RFCA.
PMID- 29948585
TI - Evaluation of right ventricular pacing parameters in patients with proliferative
scar.
AB - BACKGROUND: Dermal and myocardial injury results in a healing process,
characterized by inflammation and fibrosis. We aimed to investigate association
between proliferative scarring at the operation site and right ventricular (RV)
pacing and sensing parameters, two clinical outcomes associated with impaired
dermal and myocardial healing, respectively. METHODS: We performed an
observational retrospective study among regularly followed pacemaker
(PM)/implantable cardioverter defibrillator (ICD)-implanted patients at our
medical center. Patients, who had a first RV active fixation PM/ICD lead
implantation procedure and a minimum follow-up of 1 year, were included in the
study. Redo procedures, passive fixation RV leads, epicardial leads, generator
replacement procedures, and patients using class I and III anti-arrhythmic drugs
were excluded. Patients in the control group, matched by age, sex and implanted
device and lead type, were randomly selected from the patient pool. Lead
impedance, pacing threshold, and R wave measurements obtained at baseline and at
3rd, 6th, and 12th month were analyzed. RESULTS: Baseline characteristics of
study and control groups were similar. While baseline and follow-up lead
impedance and R wave measurements along with baseline and 3rd-month pacing
thresholds showed no significant difference between two groups, 6th- and 12th
month pacing thresholds revealed statistically significant increase in
proliferative scar group compared to control group (0.87 vs 0.72 p = 0.003 and
0.87 vs 0.71 p = 0.003, respectively). CONCLUSIONS: PM/ICD-implanted patients
with proliferative scar on pocket wound may show increased RV pacing thresholds
compared to patients with normal healing of pocket wound.
PMID- 29948586
TI - Natural progression of QRS duration in ICD-only patients.
AB - PURPOSE: The aim of our study is to determine if there is a natural progression
of QRSd in ICD-only patients. METHODS AND RESULTS: Retrospective study over a 7
year period of 86 consecutive patients who underwent ICD-only implantation in
2008 at the Liverpool Heart and Chest Hospital, UK. The mean age at ICD
implantation was 62.3 (+/- 11.5) years, range 24-82 years. Mean length of follow
up ECGs available was 5.0 (+/- 1.6) years, total of 431 patient-years. We
observed a progressive prolongation of QRSd over the 7-year study period. The
linear mixed model found a statistically significant (p < 0.001) increase in QRSd
over time, as measured in years. Clinically important progression of QRSd to >=
120 ms was observed in 30% of patients after 2.7 (+/- 1.5) years and progression
of QRSd to >= 150 ms was observed in 10% of patients after 2.9 (+/- 1.2) years.
CONCLUSIONS: The natural progression of QRS duration in ICD patients may have
serious implications for device implantation. Our study found that the QRS
duration increased at a rate of 3.1 ms per year in ICD patients.
PMID- 29948588
TI - Novel use of a 3-dimensional mapping system in cryoablation of right-sided and
septal accessory pathways: playback ablation.
AB - PURPOSE: Despite recent advances in the treatment of eliminating accessory
pathways (APs), catheter-induced mechanical block (bump) of APs has been reported
to result in a less favorable outcome with high primary failure and recurrence
rates. The real bump site cannot always be precisely reapproached under
fluoroscopy so physicians can perform ablation to a location different from where
the mechanical block was encountered. In this paper, we describe this novel use
of a 3-dimensional (3D) mapping system (playback ablation) with a case series.
METHODS: The EnSite Velocity system (St. Jude Medical, St. Paul, MN, USA), a 3D
mapping system, has a unique function that records the positional information of
catheters in a 3D geometric map and the local potential of catheters
continuously. This function enables physicians to specify the bump site in a 3D
geometric map and apply ablation to the bump site even if the catheter moves away
from the bump site. RESULTS: This technique helped us eliminate APs in two
patients with bump of APs, and they have been free of preexcitation and
arrhythmias without the use of anti-arrhythmic drugs for more than 3 months.
CONCLUSIONS: This technique may contribute to improving long-term success in
patients with mechanical block of APs.
PMID- 29948587
TI - Single 3-min freeze per vein ablation strategy with the second-generation
cryoballoon for atrial fibrillation in a large cohort of patients: long term
outcome after a single procedure.
AB - PURPOSE: The purpose of the present study was to assess the long-term success
rate of a single 3-min freeze per vein ablation strategy in the setting of
pulmonary vein isolation (PVI) by means of second-generation cryoballoon (CB-A;
Arctic Front Advance, Medtronic, Minneapolis, MN, USA) in a large cohort of
patients. METHODS: Three hundred and one patients with drug resistant atrial
fibrillation (AF) having undergone PVI by means of CB-A using a single 3-min
freeze per vein ablation strategy were included in the analysis. RESULTS:
Paroxysmal AF (PAF) was documented in 70.8% of the patients, while 29.2%
presented with persistent AF (PersAF). The mean number of CB applications was
1.09 +/- 0.3 in the left superior pulmonary vein (LSPV), 1.04 +/- 0.2 in the left
inferior pulmonary vein (LIPV), 1.12 +/- 0.3 in the right superior pulmonary vein
(RSPV), and 1.12 +/- 0.3 in the right inferior pulmonary vein (RIPV). All PVs
were successfully isolated with a 28-mm CB-A only. After a mean follow-up of 38.1
+/- 7.5 months, 207 (68.8%) patients were free of atrial tachyarrhythmia (ATa)
recurrences following a single procedure. Specifically, 72.8% of patients
presenting with PAF and 59.1% of individuals with PersAF did not experience a
recurrence. CONCLUSIONS: A single 3-min freeze per vein strategy is effective in
treating AF on a long term follow-up of 38 months. Specifically, it can afford
freedom from ATa recurrences in 72.8% of patients affected by PAF and 59.1% of
patients initially presenting with PersAF after a single CB-A procedure.
PMID- 29948589
TI - Carcinoma Cuniculatum of the Alveolar Mucosa: A Rare Variant of Squamous Cell
Carcinoma.
AB - Carcinoma cuniculatum is one of the variants of squamous cell carcinoma. It is
significantly rare with an incidence rate < 1% compared to other histological
variants of squamous cell carcinoma. Various etiologic factors implicated are
trauma, HPV, chronic inflammation and alcohol consumption but real causative
agent still remains unclear. Initially it resembles plantar wart which slowly
progress to bulky exophytic mass in the sole of the foot, where cases have been
reported first. In the oral cavity it presents clinically as an exophytic growth
and slowly invades the jaw and destroys the underlying bone. Microscopically it
exhibits as both exophytic and endophytic epithelial masses along with well
differentiated and pronounced hyperkeratosis. Treatment includes surgical
resection alone unlike other variants which are treated by radiation with or
without chemotherapy. Here we present a case of carcinoma cuniculatum occurred in
alveolar mucosa of a 47 years old female. It presented as an exophytic growth in
mandibular alveolar region, with histological features consistent with carcinoma
cuniculatum.
PMID- 29948590
TI - Stent implantation for May-Thurner syndrome with acute deep venous thrombosis:
acute and long-term results from the ATOMIC (AcTive stenting for May-Thurner
Iliac Compression syndrome) registry.
AB - The outcomes of stent implantation in managing May-Thurner syndrome (MTS) are not
well understood. To clarify the acute and long-term outcomes of stent
implantation in patients with MTS having acute deep venous thrombosis (DVT), we
retrospectively investigated consecutive 59 patients from 10 hospitals in Japan
who were treated with stents for left iliac vein stenosis with acute DVT. Stents
were considered successful if the stent was patent at discharge, which in turn
was defined as patient success. The primary endpoint for the study was stent
patency, and the secondary endpoint was recurrence of DVT and development of post
thrombotic syndrome (PTS) during follow-up. The patient success was achieved in
56 patients (95%). Clinical follow-up was conducted for 50 patients (89%) for a
median duration of 40 months (range 8-165 months). Among them, 44 patients (79%)
were followed up using imaging modalities. During this period, stent occlusion
was revealed in four patients (9%), and one patient was successfully treated
using balloon angioplasty. Primary and secondary patency rates were 84% at 19
months and 93% at 20 months, respectively. Recurrence of DVT was documented in 3
(8%) patients. PTS was evaluated from 36 patients. Three patients (8%) had PTS;
however, none of the patients had severe PTS. This multicenter retrospective
study of the use of stents for treating patients with MTS having acute DVT
demonstrated good acute and long-term outcomes and long-term stent patency.
PMID- 29948591
TI - Unexpected abrupt coronary occlusion due to arterial media in upper arm through
transradial approach.
PMID- 29948592
TI - Optical coherence tomography guidance in percutaneous coronary intervention: a
meta-analysis of randomized controlled trials.
AB - The benefit of optical coherence tomography (OCT) guidance in percutaneous
coronary intervention (PCI) is unclear. We aimed to assess the incremental value
of adding OCT to coronary angiography in PCI by meta-analytic technique. We
searched PubMed, EMBASE, Cochrane, Scopus and relevant references for randomized
studies (inception through January 5, 2018 without language restrictions) and
performed meta-analysis using random effects model. Major adverse cardiac events
(MACE), all-cause mortality, myocardial infarction, target vessel
revascularization, stent thrombosis, fluoroscopic time, contrast volume, and
procedural side effects were the measured outcomes. Five randomized studies with
a total population of 931 were analyzed. There was no difference in MACE between
angiography plus OCT and angiography alone arms (2.5 vs. 2.0% OR 1.26; 95% CI
0.40-3.99; P = 0.69; I2 = 5%). Two groups were not different in terms of all
cause mortality (0.2 vs. 0% OR 3.03; 95% CI 0.12-75; P = 0.5; I2 = not
applicable), myocardial infarction (1 vs. 0.2% OR 2.21; 95% CI 0.39-12.49; P =
0.3; I2 = 0%), target vessel revascularization (1.6 vs. 1.2% OR 1.36; 95% CI 0.4
4.4; P = 0.6; I2 = 0%), and stent thrombosis (0.2 vs. 0.5% OR 0.7; 95% CI 0.11
4.51; P = 0.7; I2 = 0%). OCT group had significantly higher fluoroscopic time and
contrast volume. Our meta-analysis shows that the addition of OCT to angiography
for PCI guidance is not associated with lower MACE, all-cause mortality,
myocardial infarction, target vessel revascularization, or stent thrombosis. It
is associated with longer fluoroscopic time and higher contrast volume.
PMID- 29948593
TI - Deep venous thrombosis, pulmonary embolism and long-distance flights.
AB - Deep vein thrombosis resulting in lethal pulmonary thromboembolism is not
infrequently encountered in forensic cases. Predisposing factors include
immobility, recent surgery, previous deep venous thromboses/pulmonary
thromboembolism, indwelling central venous lines, major trauma, the oral
contraceptive pill, pregnancy, congenital cardiac disease, sepsis, malignancy,
systemic lupus erythematosus, renal failure and certain inherited thrombophilias.
Venous thrombosis associated with air travel was reported in the early 1950's and
called the "economy class syndrome", although it is now recognized that reduced
movement on long distance flights is more significant than seating class. Long
distance flights of eight hours or more are associated with a two to fourfold
increase in the risk of deep venous thrombosis, but only in those individuals who
have underlying risk factors. With increasing numbers of flights of more than 16
h duration forensic pathologists are well placed to monitor the potential impact
of extended flying on the incidence of lethal pulmonary thromboembolism.
PMID- 29948594
TI - Complete Atrioventricular Block in an Elderly Patient Treated with Low-Dose
Lacosamide.
AB - Lacosamide, one of the last antiepileptic drugs marketed, can cause extension of
PR interval. Precautions are recommended when used in elderly and with other
drugs extending PR interval. Cases of severe third-degree atrioventricular block
have been reported only in post-marketing case reports when used at high-doses
and remain rare. We report the case of an 88-year-old woman treated with
bisoprolol, who experienced a complete atrioventricular block after initiation of
lacosamide for epilepsy associated with neurodegenerative disease. This dramatic
event required a pacemaker implementation. Not being dose-dependent (initiation
dosage used), it seemed partially explained by drug-drug interaction with
bisoprolol.
PMID- 29948595
TI - Study of Serum Metabonomics and Formula-Pattern Correspondence in Coronary Heart
Disease Patients Diagnosed as Phlegm or Blood Stasis Pattern Based on Ultra
Performance Liquid Chromatography Mass Spectrometry.
AB - OBJECTIVES: To study the characteristics of serum metabonomics in coronary heart
disease (CHD) patients diagnosed as phlegm or blood stasis pattern and explore
effects of formula-pattern correspondence treatment. METHODS: A total of 102
stable CHD patients were enrolled and divided into phlegm group (P group, n=52)
and blood stasis group (BS group, n=50) according to pattern identifification.
Gualou Xiebai Banxia Decoction (, GXBD) and Xuefu Zhuyu Decoction (, XZD) were
used as drug interventions. Relevant indicators of metabonomics were observed by
ultra performance liquid chromatography mass spectrometry (UPLC-MS) and pattern
recognition. RESULTS: Levels of amino acids and phosphatidylethanolamine (PE) in
the CHD group were much higher than those in healthy control group, while the
levels of unsaturated fatty acids, sphingosine, Lyso, phosphatidylcholine (PC)
were signifificantly lower (P<0.01). Most of the differential metabolites between
the CHD and the healthy groups were also common metabolites of phlegm and blood
stasis. 7(Z), 10(Z)-hexadecadienoic acid and DPA were decreased in the P group
and increased in the BS group. According to the quantity of retraced metabolites,
improvement in metabonomics by formula-pattern correspondence was superior to
that without correspondence in the BS group. Based on the varieties of
metabolites, GXBD could improve the levels of docosapentaenoic acid (DPA),
sphingomyelin (SM) (d34:1), and L-Lactic acid and XZD could ameliorate the levels
of sphingosine and Vit E in the P group. In the BS group, GXBD could improve
vitamin E level and XZD could make improvements in the levels of octadecanoic
acid, phosphoglycerol, and SM (d34:1). CONCLUSIONS: Phlegm and blood stasis in
CHD patients present specifific differential metabolites, and share common
metabolites. Remarkable differences have been displayed in pathological
properties and severity of phlegm and blood stasis. Patients with phlegm are more
likely to have lipid metabolism disorders. However, in patients with blood
stasis, problems mainly lie in glucose, protein and fat metabolism and the injury
of vascular cell membrane is relatively severe. The metabolic disorder is more
complicated in blood stasis pattern than that in phlegm pattern. Compared with
non-correspondence, improvement of differential metabolites is more comprehensive
and targeted in formulapattern correspondence with a better effect.
PMID- 29948596
TI - Effect of Essential Oil on Patients with Chronic Prostatitis/Chronic Pelvic Pain
Syndrome: A Pilot Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate the efficacy and safety of essential oil treatment for
type III chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: A
randomized controlled trial was conducted from December 2014 to October 2015.
Seventy type III CP/CPPS patients were assigned to the essential oil (35 cases)
or almond oil control (35 cases) group by a random number table. The oil was
smeared by self-massage on the suprapubic and sacral region once a day for 4
weeks. The National Institutes of Health Chronic Prostatitis Syndrome Index (NIH
CPSI) and expressed prostatic secretions (EPS) were examined. The primary outcome
was NIH-CPSI pain domain. The secondary outcomes included other NIH-CPSI domains
and laboratory examinations of EPS. Adverse events were also observed. RESULTS:
Sixty-six subjects completed the full 4-week treatment. There was no significant
difference between almond oil control and essential oil groups in terms of the
total score of NIH-CPSI, pain, quality of life and urination domain scores of NIH
CPSI and EPS examinations (P>0.05). In the essential oil group, pain between
rectum and testicles (perineum) in the domain of pain or discomfort was
significantly reduced at week 2 and week 4 compared with almond oil control group
(P<0.01). No serious adverse events occurred. CONCLUSION: The essential oil may
reduce the pain or discomfort in the perineum region in patients with CP/CPPS.
(Registration No. ChiCTR-IPR-14005448).
PMID- 29948597
TI - Patrinia scabiosaefolia Inhibits Growth of 5-FU-Resistant Colorectal Carcinoma
Cells via Induction of Apoptosis and Suppression of AKT Pathway.
AB - OBJECTIVE: To investigate the effects of ethanol extract of Patrinia
scabiosaefolia (EEPS) on chemo-resistance of colorectal cancer cells (CRC) and
explore the possible molecular mechanisms. METHODS: 5-fluorouracil (5-FU)
resistant human colorectal carcinoma cell line (HCT-8/5-FU) and its parental
cells HCT-8 were treated with EEPS (0, 0.25, 0.50, 1 or 2 mg/mL), or 5-FU (0,
100, 200, 400, 800 or 1600 MUmol/L). The 3-(4,5-dimethylthiazol-2-yl)-2, 5
diphenyltetrazolium bromide (MTT) assay was performed to evaluate the cell
viability. Cell density was observed by phase-contrast microscope, cell counting
and colony formation assay were used to determine the cell proliferation of HCT
8/5-FU cells treated with 0, 0.5, 1 or 2 mg/mL EEPS. Cell apoptosis was
determined by Hoechst staining. Western-blot was performed to detect the
phosphorylation of AKT as well as the protein expression level of B-cell
CLL/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax). RESULTS: Compared
with HCT-8 cells, MTT assay results indicated that HCT-8/5-FU cells were
resistant to 5-FU treatment (P<0.05), and sensitive to EEPS treatment (P>0.05).
Moreover, compared with untreated HCT-8/5-FU cells, 1 and 2 mg/mL of EEPS
treatment significantly reduced cell density, cell number, inhibited cell
survival (P<0.05), and induced apoptosis in HCT-8/5-FU cells. Furthermore, 1 and
2 mg/mL of EEPS significantly decreased the phosphorylation level of p-AKT and
Bcl-2 protein expression, and increased the expression of Bax protein (P<0.05).
CONCLUSION: EEPS is a promising therapeutic agent that may overcome chemo
resistance in cancer cells, likely through suppression of the AKT pathway and
promotion of cancer cell apoptosis.
PMID- 29948598
TI - Does anthropometric and fitness parameters mediate the effect of exercise on the
HRQoL of overweight and obese children/adolescents?
AB - BACKGROUND: There is sufficient evidence about the effects of physical exercise
programs on health-related quality of life (HRQoL) in obese and overweight
children. OBJECTIVES: The purpose of this study was to observe the effects on
physical fitness and HRQoL in overweight and obesity children and their parents
and find out whether the effect of intervention on anthropometric and physical
fitness parameters mediated the improvements found in the proxies' perception of
participant quality of life. METHODS: 151 overweight and obese children (106
intervention and 45 control) participated in a public exercise program.
Anthropometrics characteristics, physical fitness, and HRQoL (EQ-5D-Y) were
measured. Analysis of Covariance and effect size were performed to analyze the
improvement. Mediation analyzed with bootstrap to observe whether anthropometric
or physical fitness improvements mediate of the changes in the proxies'
assessment of HRQoL. RESULTS: Significant improvements were found in waist
circumference, physical fitness, and HRQoL. The improvement of waist
circumference showed a significant indirect effect on the change in the proxy
perception of quality of life. CONCLUSION: The reduction of waist circumference
mediates the change on proxies' perception of quality of life and not by the
improvement in physical fitness. TRIAL REGISTRATION: ISRCTN97887613.
PMID- 29948599
TI - Utility elicitation in adults and children for allergic rhinoconjunctivitis and
associated health states.
AB - PURPOSE: Allergic rhinitis and asthma symptoms are detrimental to health-related
quality of life (HRQoL). Health technology appraisal agencies often require cost
utility analysis when assessing new interventions. Appropriate utility estimates,
which quantify the value of different conditions in cost-utility analyses, are
scarce for allergic rhinitis and asthma health states. This study aimed to
generate utilities for allergic rhinitis and asthma health states from a European
general population sample of adults and children. METHODS: Health state
descriptions incorporating symptoms, impact of symptoms on daily life and symptom
treatment were developed using clinical guidelines. Descriptions were amended
with clinician and patient input, and incorporated into a survey in which each
health state was followed by a standard gamble (adults) or visual analogue scale
(children) item. The survey was distributed to samples of adults and children
aged 8 to 11 from four European countries that were stratified to represent the
general population within that country. RESULTS: 1454 adults and 1082 children
completed the survey. Mean health utilities ranged from 0.635 to 0.880 and those
elicited in children were lower (0.635 to 0.705) than those elicited in adults
(0.812 to 0.880). Disutilities assessing the impact of increased allergic
rhinitis severity and comorbidities were also greater in children than in adults.
CONCLUSIONS: Symptoms of allergic rhinitis and asthma were valued as having a
clinically meaningful impact on HRQoL. Children valued health states as poorer
than adults, and further research should investigate whether this reflects true
preferential differences or results from methodological and/or comprehension
differences between the two groups.
PMID- 29948600
TI - Changes in health-related quality of life (EQ-5D) dimensions associated with
community-based musculoskeletal physiotherapy: a multi-centre analysis.
AB - PURPOSE: To determine the changes in each of the five dimensions of the EuroQol 5
dimension index associated with community-based physiotherapy. METHODS: Four
thousand one hundred and thirty-six patients that received community-based
musculoskeletal physiotherapy across five NHS centres completed the EQ-5D on
entry into the service and upon discharge. Patients were categorised on symptom
location and response to treatment based on their EQ-5D index improving by at
least 0.1 ("EQ-5D responders"). For each symptom location, and for responders and
non-responders to treatment, the mean (+/- SD) were calculated for each dimension
pre- and post-treatment as well as the size of effect. RESULTS: The mobility
dimension improved (p < 0.05) in all symptom locations for EQ-5D responders (d =
0.26-1.58) and in ankle, knee, hip and lumbar symptoms for EQ-5D non-responders
(d = 0.17-0.45). The self-care dimension improved (p < 0.05) in all symptom
locations for EQ-5D responders (d = 0.49-1.16). The usual activities dimension
improved (p < 0.05) across all symptom locations for EQ-5D responders (d = 1.00
1.75) and EQ-5D non-responders (d = 0.14-0.60). Despite the pain/discomfort
dimension improving (p < 0.05) across all symptom locations for both EQ-5D
responders (d = 1.07-1.43) and EQ-5D non-responders (d = 0.29-0.66), the
anxiety/depression dimension improved (p < 0.05) from higher starting levels in
EQ-5D responders (d = 0.76-1.05) with no change seen for EQ-5D non-responders (d
= - 0.16 to 0.06). CONCLUSIONS: Clinicians should not assume that a patient
presenting with pain but expressing high anxiety/depression is unlikely to
respond to treatment, as they may show the best HRQoL outcomes. For patients
presenting with pain/discomfort and low levels of anxiety/depression, the EQ-5D
index is perhaps not a suitable tool for sole use in patient management and
service evaluation.
PMID- 29948601
TI - Association of religiosity and spirituality with quality of life in patients with
cardiovascular disease: a systematic review.
AB - PURPOSE: This review systematically identified and critically appraised the
available literature that has examined the association between religiosity and/or
spirituality (R/S) and quality of life (QOL) in patients with cardiovascular
disease (CVD). METHODS: We searched several electronic online databases (PubMed,
SCOPUS, PsycINFO, and CINAHL) from database inception until October 2017.
Included articles were peer-reviewed, published in English, and quantitatively
examined the association between R/S and QOL. We assessed the methodological
quality of each included study. RESULTS: The 15 articles included were published
between 2002 and 2017. Most studies were conducted in the US and enrolled
patients with heart failure. Sixteen dimensions of R/S were assessed with a
variety of instruments. QOL domains examined were global, health-related, and
disease-specific QOL. Ten studies reported a significant positive association
between R/S and QOL, with higher spiritual well-being, intrinsic religiousness,
and frequency of church attendance positively related with mental and emotional
well-being. Approximately half of the included studies reported negative or null
associations. CONCLUSIONS: Our findings suggest that higher levels of R/S may be
related to better QOL among patients with CVD, with varying associations
depending on the R/S dimension and QOL domain assessed. Future longitudinal
studies in large patient samples with different CVDs and designs are needed to
better understand how R/S may influence QOL. More uniformity in assessing R/S
would enhance the comparability of results across studies. Understanding the
influence of R/S on QOL would promote a holistic approach in managing patients
with CVD.
PMID- 29948602
TI - Can the e-OAKHQOL be an alternative to measure health-related quality of life in
knee osteoarthritis?
AB - OBJECTIVE: To assess the validity of the e-OAKHQOL questionnaire and analyze
whether the answers were affected by the form of administration (electronic vs.
paper). METHODS: Two samples of patients with knee osteoarthritis were
constituted. The first was recruited by general practitioners. Patients could
choose to respond to the electronic or paper version. The second included
subjects who responded to the paper version and were matched with respondents to
the electronic version in the first sample. The OAKHQOL questionnaire measures
health-related quality of life in five dimensions (43 items): physical activity,
mental health, pain, social functioning, and social support. Validity was
assessed by the classical test theory (CTT) and a Rasch measurement model
(partial credit model). RESULTS: The electronic form was preferred by 471 (89.7%)
patients: 345 were matched to respondents of the paper version. The percentage of
missing responses was lower with the electronic than paper form (1.6 vs. 2.0%, p
= .01). Rasch analysis revealed four items with underfitting. Internal
consistency was excellent for physical activity (PSI = 0.96) and mental health
(PSI = 0.93) but was slightly < 0.85 for the other dimensions. The top-down
purification highlighted the significance of DIF by gender in the pain dimension
and by form of questionnaire in the mental health dimension. CONCLUSION: CTT and
Rasch analysis demonstrated acceptable measurement properties for the five
dimensions of the e-OAKHQOL, so it may be a valuable alternative to the paper
form for measuring HRQoL.
PMID- 29948603
TI - The association between physical activity, fitness and body mass index on mental
well-being and quality of life in adolescents.
AB - PURPOSE: The purpose of the current study was to investigate the mediatory role
between vigorous physical activity, body mass index (BMI), and cardiorespiratory
fitness on symptoms of depression and their subsequent direct and indirect
effects on quality of life (QoL). METHODS: Five hundred and seventy-six
adolescents' (314 boys, 12.5 +/- 1.1 years) physical activity levels,
cardiorespiratory fitness, BMI, levels of depressive symptoms, and QoL were
measured. Structural equation modelling was used to evaluate the difference in
linear structural associations between variables. RESULTS: The model suggested
that cardiorespiratory fitness (beta = 0.16, p < 0.001) and symptoms of
depression (beta = - 0.52, p < 0.001) were both directly associated with physical
QoL, with depressive symptoms also directly influencing psychological QoL (beta =
- 0.79, p < 0.01). Body mass index was indirectly associated with physical QoL,
mediated by both symptoms of depression (beta = - 0.06, p < 0.001) and
cardiorespiratory fitness (beta = 0.05, p < 0.001) and psychological QoL mediated
by symptoms of depression (beta = - 0.09, p < 0.001). Vigorous physical activity
was indirectly associated with QoL, mediated by cardiorespiratory fitness (beta =
- 0.04, p < 0.001). CONCLUSIONS: Models suggested that vigorous physical
activity, cardiorespiratory fitness and BMI were associated, both directly and
indirectly, with mental well-being and QoL. It could, therefore, be postulated
that enhancing cardiorespiratory fitness and BMI through increasing vigorous
physical activity may be beneficial to both mental well-being and QoL in
adolescents.
PMID- 29948604
TI - Exploring the lived experience of migrants dying away from their country of
origin.
AB - PURPOSE: Migrants experience challenges settling into a new society, while
retaining their cultural and religious values. Concurrently facing an end-of-life
illness can result in existential distress affecting quality of dying. This study
aimed to explore the lived experience of migrants dying away from their country
of birth or origin. METHODS: The study design used a phenomenological approach
using Heidegger's philosophy to gather and interpret dying migrants' stories.
Participants were a purposive sample of New Zealand immigrants experiencing end
of-life illness and under hospice care. Participants were interviewed at home.
Coherent stories were drawn from the transcribed interviews and analysed using
iterative methods. Interpretive notions were formed through contemplation and
writing. RESULTS: The ten participants, seven males and three females, were of
different ethnicities and countries of origin. Three notions emerged. The first
was dual possession of a new hybrid identity developed in their adoptive country,
and an inner ethnic and cultural identity, in varying degrees of harmony with
each other. The second was being in life review-reliving homeland memories and
letting go of dreams. The third notion showed how they sought resolution by
enacting continuity through their children, hoping for a final homeland visit, or
conveying their dying wishes. CONCLUSIONS: How life review was enacted for each
migrant and resolution depended on finding some degree of belonging in their
country of adoption. Implications for end-of-life care include education to
increase practitioner awareness and use of formal and informal life review.
Enhancing spiritual well-being can assist resolution of end-of-life adjustment.
PMID- 29948605
TI - Oral health-related quality of life of children and adolescents with and without
migration background in Germany.
AB - OBJECTIVES: To compare oral health-related quality of life (OHRQoL) in children
and adolescents with and without migration background, and to assess whether
potential differences in OHRQoL can be sufficiently explained by oral health
characteristics. MATERIALS UND METHODS: A consecutive sample of 112 children and
adolescents was recruited in a German university-based orthodontic clinic, and a
convenience sample of 313 children and adolescents of German public schools was
enrolled in the study (total N = 425, age range 7-17 years). However, 29
participants were excluded due to insufficient information regarding migration
background. Accordingly, the non-migrant group consisted of 262 participants
(61.6%). For children with migration background, two groups were classified: (i)
one parent born in a foreign country (N = 41, 9.6%, single-sided migration
background), and (ii) both parents and/or child born in a foreign country ( N=
93, 21.9%, double-sided migration background). OHRQoL was assessed using the
German 19-item version of the Child Oral Health Impact Profile (COHIP-G19).
Additionally, physical oral health of 269 children with classified migration
background was determined in a dental examination. RESULTS: Overall, OHRQoL was
significantly lower in the group with double-sided migration background indicated
by lower COHIP-G19 summary scores (mean: 58.6 points) than in the group with
single-sided migration background (mean: 63.3 points) or the non-migrant group
(mean: 63.2 points). Likewise, the summary scores of the subscale "oral health
well-being" and the subscale "social/emotional, school, and self-image" were also
lower in the double-sided migrant group than in the other two groups. Linear
regression analysis showed an association between double-sided migration
background and impaired OHRQoL, even after statistically controlling for
demographic, socioeconomic, and oral health characteristics. CONCLUSION: Children
and adolescents with double-sided migration background have poorer OHRQoL than
comparably aged migrants with single-sided migration background or non
migrations. Between-group differences in OHRQoL could not be sufficiently
explained by effects of socioeconomic status or physical oral health
characteristics. Thus, other methodological, cultural, or immigration-related
factors might also play an important role for the observed effects.
PMID- 29948606
TI - Evaluation of the internal and external responsiveness of Short Form-12 Health
Survey version 2 (SF-12v2) in patients with type 2 diabetes mellitus.
AB - PURPOSE: The evidence on the responsiveness of the Short Form-12 Health Survey
version 2 (SF-12v2) in patients with type 2 diabetes mellitus (T2DM) is limited.
The aim of this study was to examine both the internal and external
responsiveness of the SF-12 measures in Chinese patients with T2DM. METHODS: A
prospective longitudinal observational study was conducted on 1443 T2DM patients
managed in public primary care clinics between 2012 and 2013. These patients were
surveyed at baseline and at 12 months using SF-12v2. The internal responsiveness
was evaluated by linear mixed effect models. Meanwhile, the external
responsiveness was tested by multiple linear regression models and receiver
operating characteristic (ROC) curve analysis. RESULTS: The internal
responsiveness of the SF-12v2 to detect negative change was satisfactory among
T2DM patients in worsened group, but only the general health domain of SF-12v2
could detect positive change among T2DM patients with improved group. For
external responsiveness, the SF-12v2 detected a significant difference-in
difference between patients with worsened and stable/improved group, but not
between patients with stable and improved group. The areas under the ROC curve
for all domains and summary scales of the SF-12v2 were not statistically
different from 0.7. CONCLUSION: This study showed that the responsiveness of SF
12v2 might not achieve the standard. Despite the wide use of the SF-12v2, we
would like to urge that both clinicians and researchers should use it with
caution in longitudinal study.
PMID- 29948607
TI - Quality of life among parents seeking treatment for their child's functional
abdominal pain.
AB - PURPOSE: Dealing with a child who suffers from functional abdominal pain (FAP) is
a major challenge for the child's parents. However, little is known about the
quality of life (QoL) of this group of parents. Therefore, this cross-sectional
study aimed to provide a comprehensive analysis of parental QoL among parents
seeking treatment for their child's abdominal pain. METHODS: 133 parents of 7-13
year-old children diagnosed with FAP reported on their health-related QoL
(HRQoL), as assessed by the SF-12, and on caregiver-related QoL, as assessed by
two CHQ-PF50 scales (emotional impact, time impact). T tests were used to compare
the parents' scores on these measures with reference scores. Subgroups which were
at risk of impairment were defined by cut-off scores. Determinants of parental
QoL were identified by hierarchical regression analyses. RESULTS: While the
parents showed significantly poorer mental health compared to population-based
reference samples (d = 0.33-0.58), their physical health did not differ. However,
parents were severely strained with respect to the time impact and emotional
impact of their child's health (d = 0.33-1.58). While 12.7-27.9% of the parents
were at risk of poor HRQoL, 60.6-70.1% were highly strained due to the demands of
their role as caregivers. Physical and mental health were best explained by
parents' psychiatric symptoms, while parents' perception of their child's
impairment additionally determined the high time and emotional impact.
CONCLUSIONS: Physical HRQoL is not impaired in the majority of parents seeking
treatment for their child's functional abdominal pain. However, the time demands
and worries due to the child's pain deserve specific attention. Psychosocial
interventions for a child's FAP should include information provided to the
parents about coping with time constraints and emotional impact. Further
prospective studies are warranted.
PMID- 29948608
TI - Effect of Replacing Cocoa Powder by Carob Powder in the Muffins on Sensory and
Physicochemical Properties.
AB - The increasing demand for cocoa and search for ingredients rich in bioactive
compounds encouraged us to investigate the possibility of replacing it by carob
powder in the muffins containing soy beans, sesame oil and flaxseeds. There was
5% addition of carob or cocoa powder to the individual doughs. The muffins with
the addition of carob were characterized by improved antiradical activity (by 36%
- 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) method, by 83% -
2,2-diphenyl-1-picrylhydrazyl (DPPH) method), higher content of genistein (18%)
and total phytosterols (17%) in the dry mass. The color differences in the carob
muffins crusts were not perceptible by consumers (DeltaE = 0.70 for crust, DeltaE
= 5.6 for crumb) and their taste was found to be less bitter and sweeter than the
taste of cocoa muffins. Moreover, the addition of carob powder as well as cocoa
powder resulted in good sensory quality. The high content of phytosterols,
genistein and improved antiradical properties proved carob to be a source of
bioactive compounds. The results show that carob powder may be used as valuable
alternative muffin ingredient to cocoa.
PMID- 29948610
TI - Working With Persons Who Inject Drugs and Live in Rural Areas: Implications From
China/Vietnam for the USA.
AB - PURPOSE OF REVIEW: To describe a small city/rural area HIV prevention project
(the Cross Border Project) implemented in Ning Ming County, Guangxi Province,
China, and Lang Son province, Vietnam, and consider its implications for
addressing the opioid/heroin epidemic in small cities/rural areas in the USA. The
description and the outcomes of the Cross Border project were taken from
published reports, project records, and recent data provided by local public
health authorities. Evaluation included serial cross-sectional surveys of people
who inject drugs to assess trends in risk behaviors and HIV prevalence. HIV
incidence was estimated from prevalence among new injectors and through BED
testing. RECENT FINDINGS: The Cross Border project operated from 2002 to 2010.
Key components of the project 2 included the use of peer outreach workers for
HIV/AIDS education, distribution of sterile injection equipment and condoms, and
collection of used injection equipment. The project had the strong support of
local authorities, including law enforcement, and the general community.
Significant reductions in risk behavior, HIV prevalence, and estimated HIV
incidence were observed. Community support for the project was maintained.
Activities have been continued and expanded since the project formally ended. The
Cross Border project faced challenges similar to those occurring in the current
opioid crisis in US small cities/rural areas: poor transportation, limited
resources (particularly trained staff), poverty, and potential community
opposition to helping people who use drugs. It should be possible to adapt the
strategies used in the Cross Border project to small cities/rural areas in the US
opioid epidemic.
PMID- 29948609
TI - Implementing Treatment of Opioid-Use Disorder in Rural Settings: a Focus on HIV
and Hepatitis C Prevention and Treatment.
AB - PURPOSE OF REVIEW: To describe the epidemiology of opioid-use disorder in the
rural United States (U.S.) as it pertains to HIV and hepatitis C transmission and
treatment resources. RECENT FINDINGS: Heroin and fentanyl analogs have surpassed
prescription opioids in their availability in rural opioid markets adding to HIV
and hepatitis C (HCV) and overdose risks. Only 18% of rural individuals live in
towns with inpatient services which are of limited quality and utility. Opioid
treatment programs that provide methadone are not located in rural areas and only
3% of the primary care providers have the ability to prescribe buprenorphine.
National models and resources have been established but lack implementation in
rural areas leading to ongoing HIV and HCV transmission and overdose. Addressing
the adverse impact of opioids in the rural U.S. will require a concerted effort
to implement effective treatments according to national standards.
PMID- 29948611
TI - Correction to: Comparison of the Amplification Refractory Mutation System, Super
Amplification Refractory Mutation System, and Droplet Digital PCR for T790 M
Mutation Detection in Non-small Cell Lung Cancer after Failure of Tyrosine Kinase
Inhibitor Treatment.
AB - The affiliation of first author (Lucheng Zhu) should be Department of Oncology,
Hangzhou Cancer Hospital and Department of Oncology, Hangzhou First People's
Hospital, Nanjing Medical University.
PMID- 29948613
TI - Transforming Growth Factor Beta 2 Inhibits Growth and Proliferation Potential of
Smad4 and p53 Mutated Human Colon Adenocarcinoma Cells.
PMID- 29948614
TI - Recent advances of Blood telomere length (BTL) shortening: A potential biomarker
for development of cancer.
AB - Telomeres, the specific DNA-protein structures remains at both ends of each
chromosome and are crucial in the maintenance of chromosome integrity and genomic
stability with protection of the chromosome from damage and degradation..
Increasing evidences suggest the correlation between telomere length and the
development of cancers, but the findings remain obscure. Generally, the average
length of telomere repeats at the ends of chromosomes that gives a clue in
providing indirect information about their mitotic history. It plays immense role
in preventing genome from nucleolytic degradation, unnecessary recombination,
repair, and interchromosomal fusion. It has major role in storing the information
in the genome. Telomere attrition during successive cell divisions induces
chromosomal instability and contributes significantly to genomic rearrangements
that can result in tumorigenesis. Convincing evidence documented that a meagre
portion of telomeric DNA is expelled out during mitotic stage of cell division.
But accelerated shortening telomere length at critical level triggers senescence
and/or apoptosis. Various harmful agents with bad lifestyles are responsible in
inducing shortening of telomere length with damage of DNA resulting to occurrence
of disease with shortening of lifespan. Besides, telomerases, the specialized
polymerase that synthesizes new telomere repeats and is strongly associated with
cancer facilitating malignant transformation. Therefore, in the study, it is
highlighted that the telomeres may play diverse roles in different cancers
whereas shortening of telomere length may be risk factors for the development of
tumors.
PMID- 29948615
TI - High-level Sp1 is Associated with Proliferation, Invasion, and Poor Prognosis in
Astrocytoma.
AB - Astrocytoma is the most common and the most lethal primary brain tumor in adults.
Grade IV glioblastoma is usually refractory to currently available surgical,
chemotherapeutic, and radiotherapeutic treatments. The Specificity protein 1
(Sp1) transcription factor is known to regulate tumorigenesis in many cancers.
The aim of this study was to investigate the clinicopathologic role of Sp1
protein in the carcinogenesis of astrocytoma. This study analyzed 98 astrocytoma
cases treated at Kaohsiung Medical University Hospital during 2002-2012.
Clinicopathologic parameters associated with Sp1 were analyzed by chi-square
test, Kaplan-Meier analysis, and Cox regression analyses. In vitro proliferation,
invasion, and migration were compared between non-siRNA groups and Sp1 siRNA
groups. In glioblastoma cells treated with Sp1 siRNA, Western blot was also used
to detect expressions of Sp1, Ki-67, VEGF, cyclin D1, E-cadherin, cleaved caspase
3 and Bax proteins. Expression of Sp1 was significantly associated with WHO grade
(p = 0.005) and with overall survival time (p < 0.001). Multivariate analysis
further revealed that prognosis of astrocytoma was significantly associated with
Sp1 expression (p = 0.036) and IDH-1 expression (p < 0.001). In vitro silencing
of Sp1 downregulated Sp1, Ki-67, and cyclin D1 but upregulated E-cadherin, Bax,
and cleaved caspase-3. These data suggest that Sp1 is a potential prognostic
marker and therapeutic target in astrocytoma.
PMID- 29948616
TI - IL-2 And IL-15 Induced NKG2D, CD158a and CD158b Expression on T, NKT- like and NK
Cell Lymphocyte Subsets from Regional Lymph Nodes of Melanoma Patients.
AB - Regional lymph nodes (LN)s represent important immunological barriers in
spreading of malignant tumors. However, they are the most frequent early
metastatic site in melanoma. Immunomodulatory agents including cytokines have
been included in therapy of melanoma and have shown severe side effects and
toxicity. In this sense, there is a growing need for bringing these agents to
further in vitro testing that may enlighten aspects of their regional
application. Therefore, the aim of this study was to investigate the effect of
interleukin (IL)-2 and IL-15, the two cytokines with similar immune-enhancing
effects, on the expression of activating NKG2D, inhibitory CD158a and CD158b
receptors on CD8+ T, NKT-like and NK cell lymphocyte subsets from regional LNs of
melanoma patients. In this study, we showed significant effects of IL-2 and IL-15
cytokine treatments on the expression of activating NKG2D and on inhibitory
CD158a and CD158b receptors on lymphocytes, CD8+ T, NKT-like and NK cell
lymphocyte subsets originating from regional LNs of melanoma patients.
Furthermore, IL-2 and IL-15 by inducing the expression of NKG2D activating
receptor on innate and on adaptive lymphocyte subsets and by augmenting NK cell
antitumor cytotoxicity that correlated with the cytokine-induced NKG2D
expression, increased antitumor potential of immune cells in regional LNs of
melanoma patients irrespective of LN involvement. These findings indicate the
importance of immune cell population from regional LNs of melanoma patients in
the development of immune intervention strategies that may if applied locally
increase antitumor potential to the level that controls tumor progressions.
PMID- 29948612
TI - Pancreatic cancer stem cells: features and detection methods.
AB - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high
incidence of distant metastasis and recurrence. Cancer stem cells (CSCs), which
are pluripotent, self-renewable, and capable of forming tumors, contribute to
PDAC initiation and metastasis and are responsible for resistance to chemotherapy
and radiation. Three types of experimental methods are commonly used to identify
CSCs: CSC-specific marker detection, a sphere-formation assay that reveals cell
proliferation under non-adherent conditions, and detection of side-population
(SP) cells that possess high intracellular-to-extracellular pump functions.
Several CSC-specific markers have been reported in PDACs, including CD133, CD24,
CD44, CXCR4, EpCAM, ABCG2, c-Met, ALDH-1, and nestin. There remains controversy
regarding which markers are specific to PDAC CSCs and which are expressed alone
or in combination in CSCs. Examining characteristics of isolated CSCs and
discovering CSC-specific treatment options are important to improve the prognosis
of PDAC cases. This review summarizes CSC-detection methods for PDAC, including
CSC-marker detection, the sphere-formation assay, and detection of SP cells.
PMID- 29948618
TI - Assessment of the circulating klotho protein in lung cancer patients.
AB - The anti-aging factor, klotho has been identified as a tumor suppressor in
various human cancers, including lung cancer. In vitro studies provided evidence
that klotho expression influences the characteristics of lung cancer cells,
however, in vivo results are lacking. The aim of our study was to evaluate
whether circulating klotho protein might serve as a potential biomarker of lung
cancer. Blood samples were taken from 45 newly diagnosed lung cancer patients (31
NSCLC, 14 SCLC) and 43 control subjects. Plasma klotho concentration was measured
using ELISA. No difference in plasma klotho values was detected between patients
and control subjects (366.3 (257.9-486.8) vs. 383.5 (304.6-489.7) pg/ml
respectively (median (IQR)); p > 0.05). Plasma klotho levels in patients with
distant metastasis did not differ from less advanced stage disease (354.2 (306.9
433.3 vs. 328.5 (242.5-419.7) pg/ml, p > 0.05). In contrast, analyzed with one
way ANOVA, significant difference (p = 0.04) was found between the examined
histological types of lung cancer: adenocarcinoma (353 (329.4-438.5) pg/ml),
squamous cell carcinoma (308 (209.6-348.1) pg/ml) and small cell lung cancer
(388.8 (289.9-495.4) pg/ml). However, Tukey's post hoc test did not reveal
significant difference between any pairs of histological groups. There was no
difference between any histological subtype and health either. Our results
suggest that circulating klotho protein cannot be considered as a biomarker for
lung cancer. Further studies are warranted in order to examine the relationship
between klotho expression in lung tissue and circulating levels of the protein,
and to explore its mechanism of action in lung cancer.
PMID- 29948617
TI - The Histone Acetylation Modifications of Breast Cancer and their Therapeutic
Implications.
AB - The histone acetylation modifications (HAMs) influence a large number of cellular
functions. They are mediated through histone acetyltransferase (HAT) and histone
deacetylase (HDAC). Nowadays, people have realized that HAMs are crucial for
development and prognosis of breast cancer. Investigations about abnormal HAMs in
breast cancer focus on initiating molecular mechanisms in breast cancer
development, identification of new biomarkers to predict breast cancer
aggressiveness and the therapeutic potential. As HAMs are reversible, breast
cancer may be treated by restoring HAMs to normal levels. Indeed, some HDAC
inhibitors have been approved by the US Food and Drug Administration to treat
certain cancers. Furthermore, HAT inhibitors, HAT activators and HDAC activators
may also be used as drugs to treat breast cancer.
PMID- 29948619
TI - Long Noncoding RNAs in Colorectal Adenocarcinoma; an in silico Analysis.
AB - Long noncoding RNAs (lncRNAs) are lengthy noncoding transcripts which are
involved in critical signaling pathways including cell cycle and apoptosis so it
is not surprising to see their altered expression in human tumors. Colorectal
adenocarcinoma is one the most frequent malignancies worldwide. The role of
lncRNAs in colorectal adenocarcinoma is not well understood. To study the
significance of lncRNAs in colorectal adenocarcinoma, we retrieved 189 approved
lncRNAs from HGNC. The genes were imported into the cBioPortal database for
transcriptomic analyses. We queried all the samples from TCGA provisional
colorectal adenocarcinoma with RNA-seq v2 data in our study and considered RNA
dysregulation with Z-score: +/-2. The lncRNA which was altered in most of the
patients were considered as "significant lncRNA" for further analyses. We
considered the association of candidate lncRNAs with clinicopathologic parameters
of samples including tumor disease anatomic site, neoplasm histologic types,
tumor stage and survival. We also compute the specificity of the significant
lncRNAs expression in colorectal adenocarcinoma comparing with other human
cancers in cancer portal. Our analysis showed that lncRNAs SNHG6, PVT1 and ZFAS1
allocated the maximum alteration among the colorectal cases. The expression of
SNHG6 and ZFAS1 was more in rectal adenocarcinoma than the colon carcinoma while
the PVT1 showed the same expression levels in both tissues. However, we found
that upregulation of PVT1 has been reduced the overall survival in patients.
Altogether these data showed SNHG6, PVT1 and ZFAS1, are promising candidates for
experimental research on colorectal adenocarcinoma to discover novel biomarker
for this prevalent cancer.
PMID- 29948620
TI - Behavior of Cutaneous Adnexal Malignancies: a Single Institution Experience.
AB - Cutaneous adnexal malignancies are biologically and pathologically diverse, and
associated with a range of clinical outcomes. Given their rarity, the prognosis
and optimal treatment of these neoplasms remains unclear. A single institution
database from a tertiary care cancer center of patients treated for malignant
cutaneous adnexal tumors was retrospectively analyzed. Clinicopathologic
variables and outcome measures were analyzed in patients undergoing wide excision
with or without sentinel node biopsy. 103 patients were analyzed; the majority of
tumors were of eccrine sweat gland derivation (n = 69, 70%), and these exhibited
a higher rate of nodal involvement and overall worse outcome. Sixteen patients
(16%) demonstrated nodal metastasis, which included 10 (10%) with nodal disease
at presentation and 6 who developed nodal metastasis during followup. 20 patients
underwent sentinel node biopsy, and 2 (10%) had a positive sentinel node. 62% of
nodal metastases occurred in patients with porocarcinoma. Seven patients died of
disease (7%) with a median time from diagnosis to death of 48 months (range, 10
174). After a median follow up of 44.7 months, age > 70 years and larger tumor
size were significantly associated with worse overall survival. Adnexal
malignancies are rare tumors, and there is a paucity of information to guide the
clinician in determining optimum surgical and medical treatment. Tumors of
eccrine derivation, especially porocarcinomas, have a high risk of nodal
involvement and may be considered for sentinel node biopsy.
PMID- 29948621
TI - Systemic Antifungal Prophylaxis in Patients Hospitalized in Hematology Units in
France: The AFHEM Cross-Sectional Observational Study.
AB - INTRODUCTION: The frequency of invasive fungal diseases (IFDs) has increased in
recent years. Within a context where both treatments and guidelines are fast
evolving, we aim to shed new light on IFD management in hematologic departments
in France. METHODS: A multicenter cross-sectional observational study was
prospectively conducted in 24 French centers in September and October 2013.
RESULTS: Four hundred ninety-four hospitalized children and adult patients
suffering from hematologic malignancy were enrolled: 147 (30%) were allogeneic
hematopoietic stem cell transplant (HSCT) recipients, 131 (27%) were patients
with acute myeloblastic leukemia or myelodysplastic syndrome (MDS), 71 (14%) were
patients with acute lymphoblastic leukemia who did not undergo allogeneic HSCT,
and the 145 (29%) remaining patients did not belong to the three above groups.
Two hundred forty-six patients (50%) received antifungal treatment, which was
prophylactic in 187 (76%) treated patients. These rates were similar across all
groups (63-80%). Patients received prophylaxis with an azole (79%), intravenous
amphotericin B formulation (10%), echinocandin (9%), or two combination drugs
(2%). CONCLUSION: Results indicate that prophylaxis is the leading antifungal
strategy in French hematology units, regardless of the disease condition,
representing 76% of prescriptions for antifungal therapy. FUNDING: Astellas
Pharma France.
PMID- 29948622
TI - Diagnosing polymyalgia rheumatica on 18F-FDG PET/CT: typical uptake patterns.
AB - OBJECTIVE: The diagnosis of polymyalgia rheumatica (PMR) is often challenging,
since similar clinical features and laboratory findings can be observed in
several inflammatory conditions. PMR involves affected sites in a specific
manner, and 18F-FDG PET/CT has the advantage for assessing the disease activity
of each site. The purpose of this study was to identify the patterns of 18F-FDG
uptake that suggest the diagnosis of PMR. METHODS: We studied 60 patients who had
undergone 18F-FDG PET/CT scans for workup of suspected PMR, arthritis,
enthesitis, or myopathy. Final diagnoses were made by board-certified
rheumatologists. The incidence of significant 18F-FDG uptake, higher than
mediastinal blood pool, of the following sites were compared among PMR patients
and patients with other diseases: wrists, elbows, shoulders, sternoclavicular
joints, acromioclavicular joints, spinous processes, ischial tuberosities, and
greater trochanters. For the spinous processes, the incidence of "Y"-shaped
uptake along the interspinous bursae was also evaluated. RESULTS: A definitive
diagnosis of PMR was given to 16 of 60 patients. The incidence of significant 18F
FDG uptake in the definitive PMR group was 6% for wrists and for elbows, 88% for
glenohumeral and sternoclavicular joints, 25% for acromioclavicular joints, 81%
for spinous processes, 69% for ischial tuberosities, and 81% for greater
trochanters. Patients with PMR showed a significantly higher incidence of "Y"
shaped uptake along the interspinous bursae than the other patients (38 vs. 9%)
(P = 0.016). CONCLUSION: 18F-FDG uptake distribution patterns and morphology can
contribute to the diagnosis of PMR. Significant 18F-FDG uptake in the
sternoclavicular joints is one of the characteristic findings in patients with
PMR as well as the uptake in the shoulders, ischial tuberosities, and greater
trochanters. "Y"-shaped spinous process uptake may be one of the specific
findings for PMR.
PMID- 29948623
TI - Willingness to Ask Tor Help Among Persons with Severe Mental illness: Call for
Research.
AB - There are times when people with severe mental illness (SMI) must be willing to
ask for help (e.g., with managing symptoms). But what makes one person ask for
help and another decide to go it alone? We used logistic regression to assess
willingness to request assistance among 150 people with SMI. Hispanics were more
likely (OR 8.51, CI 2.05-35.36, p < .01) than Caucasians to be willing to ask for
help, and people with the highest incomes (relative to the lowest) were more
likely (OR 7.23, CI 1.76-29.97, p > .01). Individuals with the most social
support (relative to the least) were more likely (OR 12.36, CI 3.01-50.85, p <
.001) to be willing to request assistance, and people who were willing to ask for
help were more likely (OR 2.07, CI 1.01-4.26, p < .05) than less willing
individuals to report being happy. More research is needed in order to better
understand predisposition to seek aid, and interventions are needed that promote
it.
PMID- 29948624
TI - Meta-Analysis of Caregiver-Directed Psychosocial Interventions for Schizophrenia.
AB - With the recent movement toward a personal-recovery paradigm to treat
schizophrenia, the locus of mental health care delivery has shifted toward
community-based care. Family caregivers comprise a substantial component of that
community, and are often providing care for longer periods, but often have no
formal training or support. Caregiver-directed psychosocial interventions (CDPI)
have been developed to train and assist caregivers in their efforts to maximize
the odds of treatment success for those in their care. This meta-analysis
compared CDPI versus treatment as usual (TAU) on outcomes such as
hospitalization, relapse, non-compliance, and "other outcomes" (emergency
services utilization, suicide attempt, and death). A systematic literature search
(2005-2015) was conducted to identify randomized controlled trials of outpatient
administered CDPI versus TAU to treat adult patients recovering from
schizophrenia. Relative risks (RR) with 95% confidence intervals derived via
random effects meta-analysis were calculated to compare CDPI versus TAU on the
aforementioned outcomes. Eighteen of the 693 citations were retained for
analysis. Overall RR for CDPI versus TAU suggested improved outcomes associated
with CDPI: hospitalization [0.62 (0.46, 0.84) p < 0.00001], relapse [0.58 (0.47,
0.73) p < 0.00001] and other outcomes [0.70 (0.19, 2.57) p = 0.59]. CDPI was
associated with significantly better compliance with medication and clinical
activities combined [0.38 (0.19, 0.74) p = 0.005]. Medication compliance alone
favored CDPI but was non-significant. Compliance with clinical activities alone
favored CDPI significantly [0.22 (0.11, 0.47) p < 0.00001]. CDPI is associated
with reductions in hospitalization, relapse, and treatment non-compliance.
PMID- 29948626
TI - Association between clinical observations and a mobile crisis team's level of
care recommendations.
AB - Mobile mental health crisis programs are a widely used and valuable community
resource. Literature analyzing the service, however, is sparse and descriptive in
nature. This study uses multinomial logistic regression to analyze clinical data
from a mobile crisis program in Pennsylvania over 12 months. 793 individuals
recommended to various levels of care were analyzed. Clinical and demographic
presentations were used as predictor variables and level of care recommendation
as outcome variable. Several clinical presentations were found to increase the
likelihood of various levels of care recommendations. These findings are
discussed in light of current suicide intervention and data-driven practice.
PMID- 29948625
TI - A Tertiary-Care/Primary-Care Partnership Aimed at Improving Care for People with
Eating Disorders.
AB - We describe the implementation and impact of a province-wide program of knowledge
exchange (KE), aimed at developing capacity for the treatment of people with
eating disorders (EDs). The program is designed to equip clinicians working in
nonspecialized health-care installations with skills to evaluate and treat people
with EDs. Trainings were conducted at 21 institutions. The majority of clinicians
reported satisfaction with the KE program and indicated that the trainings
enhanced their confidence and ability to treat patients with EDs. A subset of
clinicians received case supervision with a specialist ED therapist and followed
patients with EDs (n = 119). Treated patients showed significant improvements on
eating and depressive symptoms, and reported satisfaction with the treatments
they received.
PMID- 29948627
TI - Person-Centered Care and the Therapeutic Alliance.
AB - Person-centered care has been gaining prominence in behavioral health care, and
service planning has shifted towards "person-centered care planning" (PCCP),
where individuals, in partnership with providers, identify life goals and
interventions. A strong therapeutic alliance has been identified as key to a
person-centered approach, but little is known about how the therapeutic
relationship influences person-centered processes and outcomes. Using an
explanatory sequential mixed methods design, this study investigated: (1) the
association between the therapeutic alliance and PCCP, and (2) how the
therapeutic relationship influences the process and outcomes of PCCP.
Quantitative analyses found that a strong working alliance predicted greater
personcenteredness. Qualitative analyses revealed two central themes: (1) the
importance of connection, continuity, and calibration of the relationship to set
the right conditions for PCCP, and (2) PCCP as a vehicle for engagement. Findings
demonstrated that the therapeutic alliance is inextricably linked to the PCCP
process, each influencing the other.
PMID- 29948628
TI - Experience Focussed Counselling with Voice Hearers as a Trauma-Sensitive
Approach. Results of a Qualitative Thematic Enquiry.
AB - The individual approach of the Hearing Voices Movement, Experience Focussed
Counselling or Making Sense of Voices, claims a strong life context and trauma
focus. This qualitative study represented the first to explore whether Experience
Focussed Counselling with voice hearers, when compared to Treatment As Usual,
could be considered trauma-sensitive. Twenty-five semi-structured interviews with
voice hearers and mental health professionals in routine German mental health
settings were analysed as part of an Applied Thematic Analysis. Overall themes
identified were: trauma related; dealing with emotions; process of working with
voices; intra- and interpersonal life; and coping related. Experience Focussed
Counselling was considered helpful in understanding and working on unresolved
trauma-related areas of distress. The same did not apply to Treatment As Usual.
Findings support Experience Focussed Counselling as a trauma-sensitive
intervention in hearing voices. Frontline mental health staff can potentially
support voice hearers in identifying and working on trauma-related voices and
emotions.
PMID- 29948629
TI - Veteran Coffee Socials: A Community-Building Strategy for Enhancing Community
Reintegration of Veterans.
AB - Veterans transitioning from military to civilian life are vulnerable to a loss of
social support and an increase in isolation from their communities, which can
exacerbate other difficulties they may be experiencing, such as physical or
mental health problems. Veteran Coffee Socials are an innovative community
building pilot intervention designed to foster social support and community
between veterans. In seven target communities, certified peer specialists
initiated and facilitated weekly "Veteran Coffee Socials"-open peer support
groups for veterans, held in local coffee shop or restaurants. Over a 9-month
period, an average of 8.5 veterans attended each meeting, for a total of 2236
veteran engagements across seven towns. A range of activities were identified as
commonly occurring during these Veteran Coffee Socials. Veteran attendees
routinely formed relationships with each other, representatives from community
organizations, and staff from local and VA healthcare resources. One of the most
common activities involved veterans receiving information and directions for
enrollment into needed healthcare supports and to local community resources. Case
descriptions are provided illustrate the potential positive impact of this
intervention to build community and expand social support for returning veterans
through the examination of three individual and three group examples.
PMID- 29948630
TI - Forgiveness and Blame Among Suicide Survivors: A Qualitative Analysis on Reports
of 4-Year Self-Help-Group Meetings.
AB - This article presents the qualitative analysis of reports obtained through
participant observations collected over a 4-year period in a series of suicide
survivor self-help group meetings. It analysed how grievers' healing was managed
by their own support. The longitudinal study was focused on self/other blame and
forgiveness. Results show how self-blame was continuously present along all the
period and how it increased when new participants entered the group. This finding
indicates that self-blame characterizes especially the beginning of the
participation, and that any new entrance rekindles the problem. However, no
participant had ever definitively demonstrated self-forgiveness, while a general
forgiveness appeared when self-blame stopped. It is also suggested how to
facilitate the elaboration of self-blame and forgiveness.
PMID- 29948631
TI - Evaluating the Impact of Integrated Care on Service Utilization in Serious Mental
Illness.
AB - Serious mental illness (SMI) affects 5% of the United States population and is
associated with increased morbidity and mortality, and use of high-cost
healthcare services including hospitalizations and emergency department visits.
Integrating behavioral and physical healthcare may improve care for consumers
with SMI, but prior research findings have been mixed. This quantitative
retrospective cohort study assessed whether there was a predictive relationship
between integrated healthcare clinic enrollment and inpatient and emergency
department utilization for consumers with SMI when controlling for demographic
characteristics and disease severity. While findings indicated no statistically
significant impact of integrated care clinic enrollment on utilization, the
sample had lower levels of utilization than would have been expected. Since
policy and payment structures continue to support integrated care models, further
research on different programs are encouraged, as each setting and practice
pattern is unique.
PMID- 29948633
TI - Isolation and characterization of microsatellite markers for exploring
introgressive hybridization between the Oratosquilla oratoria complex.
AB - The Japanese mantis shrimp Oratosquilla oratoria is one of the most dominant
stomatopod species found in coastal waters of the northwestern Pacific. We
previously reported cryptic speciation and hybridization in this taxon by
integrating mitochondrial and nuclear evidence. The present study aims at
developing potential useful microsatellite markers for the O. oratoria complex
through transcriptome sequencing, with a view to reveal the occurrence of
hybridization. Of the 100 tested microsatellites, 55 were experimentally
validated. 24 of these microsatellites were transferable across different species
of the O. oratoria complex and showed polymorphic among individuals. The average
number of alleles, observed and expected heterozygosity per locus was 6.125,
0.446 and 0.577 for the temperate species, and 6.083, 0.444 and 0.578 for the
subtropical and tropical species. We also explore genetic differentiation and
hybridization between O. oratoria cryptic species using these 24 microsatellite
loci. The pairwise FST values and phylogenetic tree indicated a strong genetic
differentiation between the two cryptic species. In addition, Bayesian analysis
provided evidence for the presence of hybridization between the O. oratoria
complex. These markers provide valuable genomic resources for exploring
introgressive hybridization and expanding understanding of evolution in the O.
oratoria complex.
PMID- 29948632
TI - Mitochondrial genome analysis in penile carcinoma.
AB - Penile cancer is a rare neoplasm that seems to be linked to socio-economic
differences. Mitochondrial genome alterations are common in many tumors types and
are reported as regulating oxidative metabolism and impacting tumorigenesis. In
this study, we evaluate for the first time the mitochondrial genome in penile
carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA)
mutational load and mtDNA content in Penile tumors. Using next generation
sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and
12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and
heteroplasmy. We further evaluated variant's pathogenicity using Mutpred
predictive software and calculated mtDNA content using quantitative PCR.
Mitochondrial genome sequencing revealed an increase number of non-synonymous
variants in the tumor tissue, along with higher frequency of heteroplasmy and
mtDNA depletion in penile tumors, suggesting an increased mitochondrial
instability in penile tumors. We also described a list of mitochondrial variants
found in penile tumor and normal tissue, including five novel variants found in
the tumoral tissue. Our results showed an increased mitochondrial genome
instability in penile tumors. We also suggest that mitochondrial DNA copy number
(mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function
in PeCa. The better understanding of mitochondrial biology can bring new insights
on mechanisms and open a new field for therapy in PeCa.
PMID- 29948634
TI - Identification and expression of alternatively spliced novel isoforms of cancer
associated MYD88 lacking death domain in mouse.
AB - MYD88 is an adaptor protein known to involve in activation of NF-kappaB through
IL-1 receptor and TLR stimulation. It consists of N-terminal death domain and C
terminal Toll/IL-R homology domain that mediates its interaction with IL-1R
associated kinase and IL-1R/TLR, respectively. MYD88 contributes to various types
of carcinogenesis due to its involvement in oncogene induced inflammation. In the
present study, we have recognized two new alternatively spliced variants of MyD88
gene in mouse using bioinformatics tools and molecular biology techniques in
combination. The newly identified non-coding exon (NE-1) from 5' upstream region
alternatively splices with either exon E-2 or exon E-5 to produce two novel
transcript variants MyD88N1 and MyD88N2 respectively. The transcript variant
MyD88N1 was expressed in several tissues studied while the variant MyD88N2 was
found to be expressed only in the brain. The analysis of the upstream region of
novel exon by in silico approach revealed new promoter region PN, which possess
potential signature sequences for diverse transcription factors, suggesting
complex gene regulation. Studies of post translational modifications of
conceptualized amino acid sequences of these isoforms revealed diversity in
properties. Western blot analysis further confirmed the expression of protein
isoform MYD88N1.
PMID- 29948635
TI - Diagnostic accuracy of multi-slice computed tomography in identifying lesion
characteristics in coronary total occlusion.
AB - We performed this study to compare the sensitivity and specificity of multi-slice
computed tomography (MSCT) to coronary angiography (CA) in detecting coronary
total occlusion (CTO) lesion characteristics. Moreover, we analyzed the
association between these characteristics and the risk of revascularization
failure. Fifty patients with confirmed CTO diagnosis were tried for
revascularization using the antegrade (all 50) or retrograde (in failed nine
antegrade interventions) approaches. Each patient underwent CA and MSCT before
the intervention and data from both modalities were compared using the SPSS
software. Successful revascularization occurred in 36 (72%) and 6 (66.7%)
patients of the antegrade and retrograde groups, respectively. Compared to CA,
MSCT exhibited high sensitivity in detecting CTO segment calcification (100%),
size of the affected vessel (100%, area under the curve [AUC] = 0.82), distal
filling of the affected segment (97.7%) and side-branching at the CTO segment
(93.3%). However, it had lower sensitivity in detecting collaterals (75%) and the
length of the affected segment (87.5%, AUC = 0.77). According to MSCT data,
increased occlusion length > 18 mm (p = 0.01), atherosclerotic vessel wall (p =
0.02), small distal vessel size <= 2.75 mm (p = 0.002), proximal side-branching
(p = 0.01) and calcification of the proximal cap (p = 0.007) or distal stump (p =
0.01) were associated with an increased risk of revascularization failure. MSCT
exhibited high sensitivity in identifying several CTO lesion characteristics,
such as lesional calcification and size of the affected vessel. However, further
research is needed to improve the diagnostic accuracy of this modality and define
the predictors of revascularization failure in CTO patients.
PMID- 29948637
TI - The effect of different treatment strategies on left ventricular myocardial
deformation parameters in patients with chronic renal failure.
AB - The aim of this study was to compare left ventricular (LV) functions by speckle
tracking echocardiography (STE) in chronic kidney disease (CKD) patients in
various stages and under different renal replacement treatments in order to
evaluate possible differences between them. This prospective study included 150
patients with CKD. Renal transplantation patients with glomerular filtration rate
greater than 60 ml/min/1.73 m2, patients receiving hemodialysis three times a
week, and patients in the predialysis stage with glomerular filtration rate less
than 30 ml/dk/1.73 m2 were assigned into Group 1 (n = 50), Group 2 (n = 50), and
Group 3 (n = 50), respectively. LV longitudinal, circumferential, and radial
myocardial deformation parameters (strain, strain rate [SR], rotation, twist)
were evaluated by STE. Peak systolic longitudinal strain was higher in the
transplantation group than the hemodialysis group (- 19.93 +/- 3.50 vs - 17.47 +/
3.28%, p < 0.017). Peak systolic circumferential strain was lower in the
hemodialysis group (- 20.97 +/- 4.90%) than Groups 1 and 3 (- 25.87 +/- 4.20 and
24.74 +/- 4.55%, respectively, p < 0.001). Peak systolic radial SR was higher in
the transplantation group than the hemodialysis group (1.84 +/- 0.52 vs 1.55 +/-
0.52 s-1, respectively, p < 0.017). Other longitudinal and circumferential
deformation parameters together with peak early diastolic radial SR and twist
were also significantly different between the groups. Strain, SR, and twist
values were mostly lower in the hemodialysis patients, but generally higher in
the transplantation patients. LV functions evaluated by STE are better in the
renal transplantation patients than the hemodialysis patients and than those in
the predialysis stage. This may indicate beneficial effects of renal
transplantation on cardiac functions.
PMID- 29948638
TI - Importance of computed tomography pre-procedural planning in the customization of
a high-risk hybrid double valve intervention.
PMID- 29948636
TI - Left heart longitudinal deformation analysis in mitral regurgitation.
AB - In mitral regurgitation (MR), left atrium (LA) and left ventricle (LV) undergo
remodeling even if the patient is asymptomatic. The aim of our study was to
identify the best echo index that correlates with MR severity in asymptomatic
patients affected by MR. We enrolled 150 MR patients (50: mild, 50: moderate, 50:
severe), asymptomatic for exertional dyspnea and 50 healthy controls. MR was
graded using Doppler quantitative method. All underwent standard and Speckle
Tracking Echocardiography (STE) with analysis of global peak atrial longitudinal
strain (PALS), LV longitudinal strain (LS) and global atrio-ventricular strain
(GAVS). LA dimensions showed significant differences between the groups while LV
end-diastolic diameter did not significantly differ, although having a slight
increase. PALS was slightly higher in patients with mild MR, while decreased in
moderate and, mainly, in severe MR (controls 37.4 +/- 12.2%, mild MR 38.2 +/- 9%,
moderate MR 29.1 +/- 9%, severe MR 19.8 +/- 10.6%, p < 0.0001 by ANOVA); the same
was found for GAVS (56.1 +/- 13%, 57.6 +/- 9.7%, 48.2 +/- 9% 39 +/- 9.4%, p <
0.0001 by ANOVA). LV LS showed a tendency for gradual reduction in the three
groups. In multivariate analysis, PALS and GAVS were far superior than GLS as
predictors of MR groups. PALS emerged as an added value to the LA indexed volumes
as predictor of MR severity. STE-derived PALS and GAVS emerged as promising tools
to investigate heart longitudinal function in patients with chronic MR and no
symptoms. PALS can represent a surplus in the prediction of severity of MR, in
addition to the assessment of LA volumes.
PMID- 29948639
TI - Diffusion-weighted MRI and PET-CT in the follow up of chronic periaortitis.
AB - Aim of the present study is to compare magnetic resonance imaging (MRI) and
positron emission tomography (PET) parameters in the follow up of chronic
periaortitis (CP), with a focus on changes in the apparent diffusion coefficient
(ADC) and standardized uptake values (SUV). 127 patients with CP were treated in
our urology between 2007 and 2017. We identified 14 patients with parallel
abdominal MRI and PET-CT examinations before therapy and in the follow up
resulting in a total of 56 examinations. Relative contrast uptake and diffusion
weighted MRI parameters were compared to SUV in the corresponding PET-CT
examinationsand laboratory infection markers. All examined MRI and PET-CT
parameters showed significant changes between basis and follow-up examinations.
Median ADC values increased significantly (p < 0.001) in the follow up. SUVmax
and the other MR parameter (contrast uptake, DWI-signal) declined significantly.
We observed a strong negative correlation between ADC and SUVmax (rho: - 0.61; p
< 0.001). In addition, we found an inverse correlation of ADC with the
inflammation markers ESR (rho: - 0.64; p < 0.001) and CRP (rho: - 0.54; p =
0.001). MRI and PET-CT showed comparable results in the individual follow up of
CP and compared to laboratory inflammation markers. Our data support MRI as first
imaging modality due to absent radiation and the necessity of repetitive follow
up examinations in patients with CP.
PMID- 29948640
TI - Site-Specific Fluorescent Labeling of Antibodies and Diabodies Using
SpyTag/SpyCatcher System for In Vivo Optical Imaging.
AB - PURPOSE: Construction of antibody-based, molecular-targeted optical imaging
probes requires the labeling of an antibody with a fluorophore. The most common
method for doing this involves non-specifically conjugating a fluorophore to an
antibody, resulting in poorly defined, heterogeneous imaging probes that often
have suboptimal in vivo behavior. We tested a new strategy to site-specific label
antibody-based imaging probes using the SpyCatcher/SpyTag protein ligase system.
PROCEDURES: We used the SpyCatcher/SpyTag protein ligase system to site
specifically label nimotuzumab, an anti-EGFR antibody and an anti-HER3 diabody.
To prevent the labeling from interfering with antigen binding, we introduced the
SpyTag and SpyCatcher at the C-terminus of the antibody and diabody,
respectively. Expression and binding properties of the C-terminal antibody-SpyTag
and diabody-SpyCatcher fusions were similar to the antibody and diabody,
indicating that the SpyTag and SpyCatcher fusions were well tolerated at this
position. Site-specific labeling of the antibody and diabody was performed in two
steps. First, we labeled the SpyCatcher with IRDye800CW-Maleimide and the SpyTag
with IRDye800CW-NHS. Second, we conjugated the IRDye800CW-SpyCatcher and the
IRDye800CW-SpyTag to the antibody or diabody, respectively. We confirmed the
affinity and specificity of the IRDye800CW-labeled imaging probes using biolayer
interferometry and flow cytometry. We analyzed the in vivo biodistribution and
tumor accumulation of the IRDye800CW-labeled nimotuzumab and anti-HER3 diabody in
nude mice bearing xenografts that express EGFR and HER3, respectively. RESULTS:
Expression and binding properties of the C-terminal antibody-SpyTag and diabody
SpyCatcher fusions were similar to the antibody and diabody, indicating that the
SpyTag and SpyCatcher fusions were well tolerated at this position. We confirmed
the affinity and specificity of the IRDye800CW-labeled imaging probes using
biolayer interferometry and flow cytometry. We analyzed the in vivo
biodistribution and tumor accumulation of the IRDye800CW-labeled nimotuzumab and
anti-HER3 diabody in nude mice bearing xenografts that express EGFR and HER3,
respectively. Site-specifically IRDye800CW-labeled imaging probes bound to their
immobilized targets, cells expressing these targets, and selectively accumulated
in xenografts. CONCLUSIONS: These results highlight the ease and utility of using
the modular SpyTag/SpyCatcher protein ligase system for site-specific fluorescent
labeling of protein-based imaging probes. Imaging probes labeled in this manner
will be useful for optical imaging applications such as image-guided surgery and
have broad application for other imaging modalities.
PMID- 29948641
TI - [68Ga]RGD Versus [18F]FDG PET Imaging in Monitoring Treatment Response of a Mouse
Model of Human Glioblastoma Tumor with Bevacizumab and/or Temozolomide.
AB - PURPOSE: The aim of this study was to evaluate positron emission tomography (PET)
imaging with [68Ga]NODAGA-c(RGDfK) ([68Ga]RGD), in comparison with 2-deoxy-2
[18F]fluoro-D-glucose ([18F]FDG), for early monitoring of the efficacy of an
antiangiogenic agent associated or not with chemotherapy, in a mouse model of
glioblastoma (GB). PROCEDURES: Mice bearing U87MG human GB cells line were parted
into five groups of five mice each. One group was imaged at baseline before the
treatment phase; another group was treated with bevacizumab (BVZ), another group
with temozolomide (TMZ), another group with both agents, and the last one was the
control group. Tumors growth and biological properties were evaluated by caliper
measurements and PET imaging at three time points (baseline, during treatment t1
= 4-6 days and t2 = 10-12 days). At the end of the study, tumors were counted and
analyzed by immunohistochemistry (CD31 to evaluate microvessel density). RESULTS:
The tumor volume assessed by caliper measurements was significantly greater at t1
in the control group than in the TMZ + BVZ-treated group or in the BVZ-treated
group. At t2, tumor volume of all treated groups was significantly smaller than
that of the control group. [18F]FDG PET failed to reflect this efficacy of
treatment. In contrast, at t1, the [68Ga]RGD tumor uptake was concordant with
tumor growth in controls and in treated groups. At t2, a significant increase in
tumor uptake of [68Ga]RGD vs. t1 was only observed in the TMZ-treated group,
reflecting a lack of angiogenesis inhibition, whereas TMZ + BVZ resulted in a
dramatic tumor arrest, reduction in microvessel density and stable tumor
[68Ga]RGD uptake. CONCLUSIONS: [68Ga]RGD is a useful PET agent for in vivo
angiogenesis imaging and can be useful for monitoring antiangiogenic treatment
associated or not with chemotherapy.
PMID- 29948642
TI - Metabolic Imaging Phenotype Using Radiomics of [18F]FDG PET/CT Associated with
Genetic Alterations of Colorectal Cancer.
AB - PURPOSE: To understand the association between genetic mutations and radiomics of
2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/x
ray computed tomography (CT) in patients with colorectal cancer (CRC).
PROCEDURES: This study included 74 CRC patients who had undergone preoperative
[18F]FDG PET/CT. A total of 65 PET/CT-related features including intensity,
volume-based, histogram, and textural features were calculated. High-resolution
melting methods were used for genetic mutation analysis. RESULTS: Genetic mutants
were found in 21 KRAS tumors (28 %), 31 TP53 tumors (42 %), and 17 APC tumors (23
%). Tumors with a mutated KRAS had an increased value at the 25th percentile of
maximal standardized uptake value (SUVmax) within their metabolic tumor volume
(MTV) (P < .0001; odds ratio [OR] 1.99; 95 % confidence interval [CI] 1.37-2.90)
and their contrast from the gray-level cooccurrence matrix (P = .005; OR 1.52; 95
% CI 1.14-2.04). A mutated TP53 was associated with an increased value of short
run low gray-level emphasis derived from the gray-level run length matrix (P =
.001; OR 243006.0; 95 % CI 59.2-996,872,313). APC mutants exhibited lower low
gray-level zone emphasis derived from the gray-level zone length matrix (P =
.006; OR < .0001; 95 % CI 0.000-0.22). CONCLUSION: PET/CT-derived radiomics can
provide supplemental information to determine KRAS, TP53, and APC genetic
alterations in CRC.
PMID- 29948643
TI - SNAPshots of the MCHR1: a Comparison Between the PET-Tracers [18F]FE@SNAP and
[11C]SNAP-7941.
AB - PURPOSE: The melanin-concentrating hormone receptor 1 (MCHR1) has become an
important pharmacological target, since it may be involved in various diseases,
such as diabetes, insulin resistance, and obesity. Hence, a suitable positron
emission tomography radiotracer for the in vivo assessment of the MCHR1
pharmacology is imperative. The current paper contrasts the extensive in vitro,
in vivo, and ex vivo assessments of the radiotracers [18F]FE@SNAP and [11C]SNAP
7941 and provides comprehensive information about their biological and
physicochemical properties. Furthermore, it examines their suitability for first
in-man imaging studies. PROCEDURES: Kinetic real-time cell-binding studies with
[18F]FE@SNAP and [11C]SNAP-7941 were conducted on adherent Chines hamster ovary
(CHO-K1) cells stably expressing the human MCHR1 and MCHR2. Small animal imaging
studies on mice and rats were performed under displacement and baseline
conditions, as well as after pretreatment with the P-glycoprotein/breast cancer
resistant protein inhibitor tariquidar. After the imaging studies, detailed
analyses of the ex vivo biodistribution were performed. Ex vivo metabolism was
determined in rat blood and brain and analyzed at various time points using a
quantitative radio-HPLC assay. RESULTS: [11C]SNAP-7941 demonstrates high uptake
on CHO-K1-hMCHR1 cells, whereas no uptake was detected for the CHO-K1-hMCHR2
cells. In contrast, [18F]FE@SNAP evinced binding to CHO-K1-hMCHR1 and CHO-K1
hMCHR2 cells. Imaging studies with [18F]FE@SNAP and [11C]SNAP-7941 showed an
increased brain uptake after tariquidar pretreatment in mice, as well as in rats,
and exhibited a significant difference between the time-activity curves of the
baseline and blocking groups. Biodistribution of both tracers demonstrated a
decreased uptake after displacement. [11C]SNAP-7941 revealed a high metabolic
stability in rats, whereas [18F]FE@SNAP was rapidly metabolized. CONCLUSIONS:
Both radiotracers demonstrate appropriate imaging properties for the MCHR1.
However, the pronounced metabolic stability as well as superior selectivity and
affinity of [11C]SNAP-7941 underlines the decisive superiority over [18F]FE@SNAP.
PMID- 29948645
TI - Patient Activation Mediates the Association Between Psychosocial Risk Factors and
Spine Surgery Results.
AB - Although spine surgery (SS) and spinal cord stimulators (SCSs) can provide
significant relief for patients with intractable pain, their effectiveness is
variable. Previously, a number of pre-operative psychosocial risk factors have
predicted suboptimal outcomes of these procedures. However, recent research has
found that "patient activation"-the extent to which patients are engaged and
active in their own health care-can predict positive surgical results. The
purpose of the current investigation was to determine whether patient activation
helps explain associations between established psychosocial risk factors and
suboptimal outcomes. Candidates for SS and SCS (n = 1254; 56.3% women, mean age
50.4 years) consented to participate in an outcome study prior to their pre
surgical psychological evaluation. Of those, 46.3% returned self-report measures
an average of 180 days (SD = 79.1) post-surgery. Bootstrapped mediation analyses
indicated that patient activation mediates numerous associations between
psychosocial risk factors and suboptimal outcomes. That is, patients' involvement
in obtaining information, decision making, and their resilience can explain why
some patients do not experience adverse surgical results when pre-surgical
psychosocial risk factors are present. Pre-surgical psychological evaluations
should include examination of patient strengths in addition to psychosocial risk
factors, so that treatments can be appropriately individualized and the most
effective surgical results obtained.
PMID- 29948644
TI - Recent Advances in the Biology and Treatment of T Cell Acute Lymphoblastic
Leukemia.
AB - PURPOSE OF REVIEW: This article provides an overview of the current knowledge
regarding the biology and treatment of T cell acute lymphoblastic leukemia (T
ALL) and highlights the most recent findings in this field over the past 5 years.
RECENT FINDINGS: Remarkable progress has been made in the genomic landscape of T
ALL over the past few years. The discovery of activating mutations of NOTCH1 and
FBXW7 in a majority of patients has been a seminal observation, with several
early phase clinical trials currently exploring these as potential therapeutic
targets. Characterization of early T cell precursor ALL, incorporation of minimal
residual disease assessment into therapeutic protocols, and use of pediatric
intensive regimens along with judicious use of allogeneic HCT have significantly
improved risk stratification and treatment outcomes. Improved risk stratification
and the use of novel targeted therapies based on recent genomic discoveries are
expected to change the therapeutic landscape of T-ALL and hopefully improve the
outcomes of this historically poor prognosis disease.
PMID- 29948646
TI - The Role of Disease Conviction: Exploring Its Effects on Chest Pain and Anxiety
Related Models of Non-cardiac Chest Pain.
AB - The aim of this study was to investigate the role of disease conviction in the
chest pain and life interference of patients with non-cardiac chest pain (NCCP),
after controlling for anxiety sensitivity and body vigilance. While all three
psychological constructs are theoretically implicated and empirically associated
with the experience of NCCP, no research has examined the influence of disease
conviction in the context of other relevant constructs. The sample included 229
participants with NCCP who were recruited after a medical evaluation failed to
elicit an organic explanation for their chest pain. Hierarchical regression
analyses revealed that while anxiety sensitivity significantly predicted chest
pain severity and interference, only body vigilance contributed significant
additional variance to chest pain severity, and only disease conviction
contributed significant additional variance to chest pain interference. While
anxiety sensitivity, body vigilance, and disease conviction all appear to affect
those with NCCP, it seems that their impact is manifest in different domains
(i.e., pain perception vs. psychosocial impairment).
PMID- 29948648
TI - Long non-coding RNA p10247, high expressed in breast cancer (lncRNA-BCHE), is
correlated with metastasis.
AB - Recent studies have shown that long non-coding RNAs (lncRNAs) have key functions
during breast cancer development. Considering the complexity of IncRNAs
regulatory network, the identification of novel and functional lncRNAs associated
with breast cancer is thus very important. By using Agilent LncRNA Human Gene
Expression Microarray, we identified a number of lncRNAs that were differentially
expressed in breast cancer compared to their corresponding adjacent tissues.
According to the microarray, the expression of p10247, henceforth named as lncRNA
BCHE (standing for lncRNA high expressed in breast cancer), was found to be
uniformly higher in all the five breast cancer tissues tested, and this was
further confirmed in 56 breast cancer tissues by real-time RT-PCR. The function
of lncRNA-BCHE in breast cancer cells was tested by knockdown and over-expression
experiments in vitro. We also analyzed the public cohorts of breast cancer
patients on the Kaplan Meier plotter platform. Clinical analysis revealed that
the expression of lncRNA-BCHE was significantly correlated with advanced clinical
stage and lymph node metastasis. Our data indicate that lncRNA-BCHE regulates the
growth, migration and invasion of breast cancer cells. In addition, we found that
these functions are mediated, at least in part, by the regulation of integrin
subunit beta 1 (ITGB1) levels. The expression of ITGB1 serves as a negative
prognostic factor and metastasis risk predictor in breast cancer, irrespective of
subtype and therapeutic regimen. In summary, our results suggest that lncRNA-BCHE
is an oncogenic lncRNA enhancing the growth and metastatic potential of breast
cancer cells, and a potential predictor of breast cancer metastatic progression.
PMID- 29948650
TI - Cancer Knowledge Among Mexican Immigrant Farmworkers in North Carolina.
AB - Latino farmworkers are exposed to a number of carcinogens in the workplace.
Cancer survival rates for Latinos are below average. This paper describes Mexican
immigrant farmworkers' knowledge of colorectal, breast, and testicular cancer,
and compares farmworkers' cancer knowledge to that of other Mexican immigrants.
Survey interviews for this study were conducted with 100 farmworkers and 100 non
farmworkers in 2015 in North Carolina as part of an ongoing community-based
participatory research project. We found low to moderate levels of knowledge
about colorectal, breast, and testicular cancer among farmworkers. Compared to
non-farmworkers, farmworkers had similar levels of knowledge about breast and
testicular cancer, but slightly lower knowledge about colorectal cancer (p =
0.0087). Few studies have used quantitative methods to assess farmworkers'
knowledge of specific types of cancer. Our results demonstrate a need for
increased dissemination of existing cancer education programs and further
research to develop additional educational tools.
PMID- 29948651
TI - Prevalence and Perception of Obesity Among Sub-Saharan Africans in Korea.
AB - There is a dearth of obesity study among sub-Saharan African immigrants in Seoul,
Korea. We investigated the prevalence and perception of obesity among this
population. A cross-sectional study involving 211 immigrants aged 20 years and
above from sub-Saharan Africa was carried out, using a structured questionnaire.
Obesity (BMI >= 30.0 kg/m2) was calculated as the primary outcome variable. The
overall prevalence of obesity was 27.0% (men 22.6% and women 36.8%). In a
logistic regression analysis adjusting for age, obesity was significantly
associated with increased duration of residence. Participants were 4.03 (95% CI
1.63-9.94) more likely to disagree than agree that obesity is a sign of wealth
and that it gives respect. There is an urgent need to assess the possible factors
predisposing sub-Saharan Africans to obesity and interventions should be designed
targeting their lifestyle modification for healthy weight.
PMID- 29948649
TI - Isolated pancreatic metastases from renal cell carcinoma: an outcome of a special
metastatic pathway or of specific tumor cell selection?
AB - Isolated pancreatic metastases (isPM) are a rare metastasizing pattern in the
natural history of renal cell cancer. Their clinical hallmark is that they are
confined to a single organ, the pancreas, while all other organs are unaffected
for a long time. Almost all workers in the field suggested that mechanical tumor
cell propagation to the pancreas may be the mechanism underlying this
metastasizing pattern. In 2006 our group, by contrast, proposed an alternative
mechanism, i.e. a special affinity of the tumor cells for the pancreas. In the
present study an attempt was made to shed more light on the settlement of isPM by
reviewing recent literature data. 666 observations of isPM reported in the
literature were reviewed. The analyses showed that local lymphatic spread does
not play a major role because the lymphatic system is, in general, rarely
involved in isPM. This also applies to a local venous spread, because the site of
pancreatic metastases is independent of the side affected by the primary renal
cancer. But the results are compatible with a systemic metastatic pathway. That
metastases in other organs, which would be expected given a systemic spread, are
absent can plausibly be explained by a seed and soil mechanism: only the pancreas
offers the tumor cell emboli an environment which is conducive to the growth of
clinically manifest metastases, while settlement of metastatic tumor cells is
prevented in all other organs.
PMID- 29948647
TI - The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome.
AB - Epithelial mesenchymal transition (EMT) describes the shift of cells from an
epithelial form to a contact independent, migratory, mesenchymal form. In cancer
the change is linked to invasion and metastasis. Tumour conditions, including
hypoxia, acidosis and a range of treatments can trigger EMT, which is implicated
in the subsequent development of resistance to those same treatments.
Consequently, the degree to which EMT occurs may underpin the entire course of
tumour progression and treatment response in a patient. In this review we look
past the protective effect of EMT against the initial treatment, to the role of
the mesenchymal state, once triggered, in promoting disease growth, spread and
future treatment insensitivity. In patients a correlation was found between the
propensity of a treatment to induce EMT and failure of that treatment to provide
a survival benefit, implicating EMT induction in accelerated tumour progression
after treatment cessation. Looking to the mechanisms driving this detrimental
effect; increased proliferation, suppressed apoptosis, stem cell induction,
augmented angiogenesis, enhanced metastatic dissemination, and immune tolerance,
can all result from treatment-induced EMT and could worsen outcome. Evidence also
suggests EMT induction with earlier therapies attenuates benefits of later
treatments. Looking beyond epithelial tumours, de-differentiation also has
therapy-attenuating effects and reversal thereof may yield similar rewards. A
range of potential therapies are in development that may address the diverse
mechanisms and molecular control systems involved in EMT-induced accelerated
progression. Considering the broad reaching effects of mesenchymal shift
identified, successful deployment of such treatments could substantially improve
patient outcomes.
PMID- 29948652
TI - Endocannabinoid hydrolase and cannabinoid receptor 1 are involved in the
regulation of hypothalamus-pituitary-adrenal axis in type 2 diabetes.
AB - Hypothalamus-pituitary-adrenal (HPA) axis, as the key moderator in energy
metabolism, plays an important role in diabetes. The endogenous cannabinoid
system (eCBs) involves in neuronal functions, and simultaneously cannabinoid
receptors are almost expressed in all regions of the hypothalamus according to a
spate of reports. However, few data investigate the changes of eCBs and HPA axis
in type 2 diabetes. In this study, five diabetes mellitus rhesus monkeys, five
prediabetes rhesus monkeys and five healthy rhesus monkeys were observed. In the
present study, we detected cell swelling and necrosis extensively in the
paraventricular nucleus (PVN) and neurohypophysis in prediabetes and overt
diabetes monkeys. The adrenocorticotropic hormone in the pituitary gland,
adrenocorticotropic hormone receptor, and 11beta-hydroxysteroid dehydrogenase in
the adrenal gland were all hyper-secreted and expressed from healthy to overt
diabetes. Meanwhile, the cortisol concentration in the adrenal gland was
increased along with the progress of diabetes. It could be concluded that
hyperfunction of the HPA axis exists in the type 2 Diabetes pathogenesis.
However, we also found a weakened expression and secretion of corticotrophin
releasing hormone and glucocorticoids receptor in PVN. The expression of
corticotropin releasing hormone receptor 1 in pituitary gland decreased in
prediabetes monkeys, but increased in overt diabetes monkeys. The downregulation
of cannabinoid receptor 1 and upregulation of monoglycerol lipase and fatty acid
amide hydrolase in PVN was involved in the pathogenesis of type 2 diabetes.
Collectively, we can conclude that changes in endocannabinoid hydrolase and
cannabinoid receptor might indicate the effect of downregulation of eCBs. It can
be assumed that hyper-function of the HPA axis from healthy to overt diabetes is
due to the undermining inhibition of eCBs. However, the regulatory mechanism of
eCBs targets on the HPA axis need to be further explored.
PMID- 29948653
TI - Early liver transplantation in neonatal-onset and moderate urea cycle disorders
may lead to normal neurodevelopment.
AB - Urea cycle disorders (UCDs) are inherited metabolic diseases that lead to
hyperammonemia. Neurodevelopmental outcomes of patients with UCDs depend on the
maximum ammonia concentration (MAC) in the blood during onset. MAC >=360 MUM is a
marker of poor neurodevelopmental outcomes. We investigated the
neurodevelopmental outcomes and MAC at onset for 177 patients with UCDs in Japan
(median age, 8 years and 2 months; range, 10 days-72 years), including 57
patients with male ornithine transcarbamylase (OTCD), 59 patients with female
OTCD, 23 patients with carbamoyl-phosphate synthetase 1 deficiency (CPSD), 28
patients with arginosuccinate synthetase deficiency, 9 patients with
arginosuccinate lyase deficiency (ALD), and 1 patient with arginase 1 deficiency.
Neurodevelopmental outcomes of patients with CPSD and ALD were poor because most
had neonatal onset with blood MAC >=300 MUM at onset. Although OTCD, particularly
female late-onset OTCD, has good neurodevelopmental outcomes among those with
UCDs, it is not necessarily a mild disease with good long-term outcomes. Patients
with severe UCDs and MAC >=300 MUM at onset should undergo liver transplantation
(LT). Moreover, this study suggested that if the onset of UCD began during the
neonatal period, then even UCD patients with MAC <300 MUM at onset should undergo
LT to protect the brain.
PMID- 29948654
TI - The influence of blood phenylalanine levels on neurocognitive function in adult
PKU patients.
AB - It is well known that hyperphenylalaninemia caused by phenylketonuria (PKU)
negatively influences cognitive performance. Several tests have been used to
study these functions. Until now, no universal, optimal tool has been developed
for detecting PKU-caused brain dysfunctions. Using computerized
neuropsychological tests during daily routine would be helpful for screening
subclinical brain deficits in adult PKU patients. In a monocentric, cross
sectional study, adult patients with PKU (n = 46; median age = 29.5 years;
female/male ratio = 21/25) were tested with the computerized Cambridge Cognition
(CANTAB) test measuring neurocognitive functions. Patients were divided into two
groups: The "on diet" group included patients whose blood Phe-level was under 600
MUmol/l (n = 20), and the "loose diet" group included patients whose blood Phe
level was above 600 MUmol/l (n = 26) at the examination time. The results of the
PKU-affected individuals were compared with a healthy control group (n = 31;
median age = 25 years; female/male ratio = 11/20). Compared with the control
group, PKU patients had significantly worse test results in memory, problem
solving skills, and strategy. However, there were no significant differences in
response speed or initial thinking time. There was no correlation between the
blood Phe-level, tyrosine (Tyr)-level or Phe/Tyr ratio and the different
cognitive test results. There were no significant differences in test results
between the two PKU subgroups. Several cognitive functions measured by CANTAB are
negatively influenced by hyperphenylalaninemia in adult PKU patients. However,
response speed and initial thinking time were not impaired as seriously as other
functions. Patients with lower Phe-levels failed to achieve better test results
than patients whose Phe-levels were notably elevated.
PMID- 29948655
TI - Probiotics decrease depressive behaviors induced by constipation via activating
the AKT signaling pathway.
AB - Chronic constipation is often accompanied by emotional disorders such as
depression and anxiety. The aim of this study was to determine whether
administration of a multispecies probiotic can decrease depressive behaviors
through the gut-brain axis and identify any underlying mechanisms. A mouse model
of constipation induced by loperamide (5 mg.kg-1,i.p.) was used. For that
purpose, 36 ICR male mice were divided into three groups: control, constipation
and probiotic groups. The probiotic group received treatment with a probiotic
once per day for 14 days via a gavage. All other groups were given an equal
volume of normal saline. The fecal parameters and intestinal transit ratio were
recorded. The forced swimming test and tail suspension test were used to detect
changes in depressive behaviors. Total superoxide dismutase (T-SOD) activity and
malondialdehyde (MDA) levels were measured by assay kits. We also detected
neuronal survival, as well as phosphorylated Ser/Thr protein kinase (p-AKT), Bcl
2, Bcl-2 associated X protein (Bax) and cleaved caspase-3 levels in the
hippocampus. The results showed that administration of a probiotic could
ameliorate depressive behaviors and relieve neuronal cell injury in the
hippocampal CA3 regions. Moreover, probiotic treatment decreased MDA levels and
increased SOD activity. Furthermore, probiotic administration increased p-AKT and
Bcl-2 levels in the hippocampus of the constipated mice, while decreasing the
concentrations of Bax and cleaved caspase-3, so as to inhibit the neural
apoptosis. In the present study, we confirm that probiotics can alleviate
depression induced by constipation through protecting neuronal health via
activation of the AKT signaling pathway.
PMID- 29948656
TI - Gentiopicroside abrogates lipopolysaccharide-induced depressive-like behavior in
mice through tryptophan-degrading pathway.
AB - Targeting neuroinflammatory disturbances has been acknowledged as a potential
strategy for treatment of depressive disorder in humans. Over-activation of
tryptophan-degrading pathway by pro-inflammatory cytokines resulted in N-methyl-d
aspartate (NMDA)-mediated excitotoxicity, which is implicated in pathophysiology
of depression. Gentiopicroside (Gent) has powerful anti-inflammatory property and
exhibits promising antidepressant effect in an animal model of pain/depression
dyad by down-regulating GluN2B-containing NMDA receptors. Therefore, the present
study aimed to investigate the ability of Gent to abolish depressive-like
behavior induced by lipopolysaccharide (LPS) in mice. Acute administration of LPS
(0.5 mg/kg, i.p.) increased immobility time in both forced swimming test (FST)
and tail suspension test (TST) without affecting spontaneous locomotor activity,
indicative of depressive-like behavior. Gent (50 mg/kg, i.p.) administered once a
day for three consecutive days prevented the development of depressive-like
behavior induced by LPS. The antidepressant-like effect was paralleled with
restoration of LPS-induced alterations in brain inflammatory mediators (i.e. IL
1beta and TNF-alpha). In addition, Gent prevented over-activation of indoleamine
2,3-double oxygen enzyme (IDO) and recovered GluN2B subunit expression in the PFC
challenged by LPS. In conclusion, our results suggested that Gent pretreatment
provided protection against LPS-induced depressive-like behavior and the effect
appeared to be demonstrated, at least partially, by blocking various steps of
tryptophan-degrading pathway.
PMID- 29948657
TI - High-level expression of the HIV entry inhibitor griffithsin from the plastid
genome and retention of biological activity in dried tobacco leaves.
AB - KEY MESSAGE: The potent anti-HIV microbicide griffithsin was expressed to high
levels in tobacco chloroplasts, enabling efficient purification from both fresh
and dried biomass, thus providing storable material for inexpensive production
and scale-up on demand. The global HIV epidemic continues to grow, with 1.8
million new infections occurring per year. In the absence of a cure and an AIDS
vaccine, there is a pressing need to prevent new infections in order to curb the
disease. Topical microbicides that block viral entry into human cells can
potentially prevent HIV infection. The antiviral lectin griffithsin has been
identified as a highly potent inhibitor of HIV entry into human cells. Here we
have explored the possibility to use transplastomic plants as an inexpensive
production platform for griffithsin. We show that griffithsin accumulates in
stably transformed tobacco chloroplasts to up to 5% of the total soluble protein
of the plant. Griffithsin can be easily purified from leaf material and shows
similarly high virus neutralization activity as griffithsin protein recombinantly
expressed in bacteria. We also show that dried tobacco provides a storable source
material for griffithsin purification, thus enabling quick scale-up of production
on demand.
PMID- 29948658
TI - Genome-wide analysis of the invertase gene family from maize.
AB - KEY MESSAGE: The recent release of the maize genome (AGPv4) contains annotation
errors of invertase genes and therefore the enzymes are bestly curated manually
at the protein level in a comprehensible fashion The synthesis, transport and
degradation of sucrose are determining factors for biomass allocation and yield
of crop plants. Invertase (INV) is a key enzyme of carbon metabolism in both
source and sink tissues. Current releases of the maize genome correctly annotates
only two vacuolar invertases (ivr1 and ivr2) and four cell wall invertases
(incw1, incw2 (mn1), incw3, and incw4). Our comprehensive survey identified 21
INV isogenes for which we propose a standard nomenclature grouped
phylogenetically by amino acid similarity: three vacuolar (INVVR), eight cell
wall (INVCW), and ten alkaline/neutral (INVAN) isogenes which form separate
dendogram branches due to distinct molecular features. The acidic enzymes were
curated for the presence of the DPN tripeptide which is coded by one of the
smallest exons reported in plants. Particular attention was placed on the
molecular role of INV in vascular tissues such as the nodes, internodes, leaf
sheath, husk leaves and roots. We report the expression profile of most members
of the maize INV family in nine tissues in two developmental stages, R1 and R3.
INVCW7, INVVR2, INVAN8, INVAN9, INVAN10, and INVAN3 displayed the highest
absolute expressions in most tissues. INVVR3, INVCW5, INVCW8, and INVAN1 showed
low mRNA levels. Expressions of most INVs were repressed from stage R1 to R3,
except for INVCW7 which increased significantly in all tissues after flowering.
The mRNA levels of INVCW7 in the vegetative stem correlated with a higher
transport rate of assimilates from leaves to the cob which led to starch
accumulation and growth of the female reproductive organs.
PMID- 29948660
TI - Tailored treatment for signet ring cell gastric cancer.
AB - Gastric cancer with Lauren diffuse types is increasing in the West. The raising
trend is more evident when considering signet ring cells (SRC) histology.
However, to control the biologic potential of this GC subtype, some hypotheses of
tailored therapeutic strategies for SRC cancers have been made. A review of the
literature was performed using the key words "signet ring cells" AND "gastric
cancer". Results of literature review were descriptively reported. Endoscopic
submucosal dissection (ESD), according to the Japanese extended criteria, could
be a therapeutic option for early SRC tumours. However, according to the
evidences from more recent studies, indications for ESD to these tumours types
should be carefully considered. Concerning the optimal surgical treatment,
considering the high lymphotropism and infiltrating behaviour of SRC histotype,
the extension of gastric resection should be wider than for intestinal type
cancer and laparoscopic surgery should be performed carefully. Moreover, D3
lymphadenectomy could provide a benefit in diffuse-type and SRC histology. The
role of surgery in gastric cancer with peritoneal carcinomatosis is still debated
and studies on this topic should stratify the good results according to GC
histotype. Finally, despite the evidences of chemoresistance in SRC, ongoing
randomized trials suggest that multimodal therapy could be the best treatment.
Based on the assumption that SRC tumours have specific features, they deserve a
specific multimodal treatment. However, a preliminary step to generate strong
evidences in this field is the standardization of terminology used to define
signet ring cells carcinoma.
PMID- 29948659
TI - An armadillo-domain protein participates in a telomerase interaction network.
AB - KEY MESSAGE: Arabidopsis and human ARM protein interact with telomerase.
Deregulated mRNA levels of DNA repair and ribosomal protein genes in an
Arabidopsis arm mutant suggest non-telomeric ARM function. The human homolog
ARMC6 interacts with hTRF2. Telomerase maintains telomeres and has proposed non
telomeric functions. We previously identified interaction of the C-terminal
domain of Arabidopsis telomerase reverse transcriptase (AtTERT) with an
armadillo/beta-catenin-like repeat (ARM) containing protein. Here we explore
protein-protein interactions of the ARM protein, AtTERT domains, POT1a, TRF-like
family and SMH family proteins, and the chromatin remodeling protein CHR19 using
bimolecular fluorescence complementation (BiFC), yeast two-hybrid (Y2H) analysis,
and co-immunoprecipitation. The ARM protein interacts with both the N- and C
terminal domains of AtTERT in different cellular compartments. ARM interacts with
CHR19 and TRF-like I family proteins that also bind AtTERT directly or through
interaction with POT1a. The putative human ARM homolog co-precipitates telomerase
activity and interacts with hTRF2 protein in vitro. Analysis of Arabidopsis arm
mutants shows no obvious changes in telomere length or telomerase activity,
suggesting that ARM is not essential for telomere maintenance. The observed
interactions with telomerase and Myb-like domain proteins (TRF-like family I) may
therefore reflect possible non-telomeric functions. Transcript levels of several
DNA repair and ribosomal genes are affected in arm mutants, and ARM, likely in
association with other proteins, suppressed expression of XRCC3 and RPSAA
promoter constructs in luciferase reporter assays. In conclusion, ARM can
participate in non-telomeric functions of telomerase, and can also perform its
own telomerase-independent functions.
PMID- 29948661
TI - Gastric cancer surgery.
PMID- 29948662
TI - Self-fixing parietex progrip versus the standard sutured prolene mesh in tension
free repair of inguinal hernia: effect on testicular volume and testicular blood
flow.
AB - Our study was conducted to compare self-fixing lightweight polyester mesh (group
I) to the standard heavy weight polypropylene mesh (group II) using tension-free
Lichtenstein hernioplasty as regard to the effect of mesh implantation and
perimesh fibrosis on testicular blood flow. 80 patients with uncomplicated
inguinal hernia were divided in two groups. Doppler ultrasonography measured
testicular volume, testicular artery velocity preoperative and 3rd month post
operative. Blood flow in the testicles was represented by resistive index (RI).
No case of testicular atrophy occurred in either group, however, in both groups a
significant postoperative decrease in testicular volume (p = 0.001 in group I and
p < 0.001 in group II) was accompanied by a significant increase in RI as
compared to their pre-operative values (p < 0.001 in group I and p = 0.009 in
group II). Comparing the two groups, patients in group I showed higher values of
decrease in testicular volume accompanied by more increase in RI values
postoperatively compared to group II patients, but these values did not reach a
significant value (p = 0.107, p = 0.136). There was a significant increase in the
number of post-operative varicocele and hydrocele in group I compared to group
II. Mesh implantation has an effect on testicular size and blood flow by
decreasing the testicular size and increasing the RI. This effect was more
obvious in the parietex progrip. Although there is an indirect relation between
RI and the sperm count, testicular blood flow alone is not enough to judge
fertility.
PMID- 29948663
TI - BGP-15 improves contractile function of regenerating soleus muscle.
AB - This study investigated the effect of the heat shock protein inducer O-[3
piperidino-2-hydroxy-1-propyl]-nicotinic amidoxime (BGP-15) on the morphology and
contractile function of regenerating soleus muscles from mice. Cryolesioned
soleus muscles from young mice treated daily with BGP-15 (15 mg/Kg) were
evaluated on post-cryolesion day 10. At this time point, there was a significant
decrease in the cross-sectional area of regenerating myofibers, maximal force,
specific tetanic force, and fatigue resistance of regenerating soleus muscles.
BGP-15 did not reverse the decrease in myofiber cross-sectional area but
effectively prevented the reduction in tetanic force and fatigue resistance of
regenerating muscles. In addition, BGP-15 treatment increased the expression of
embryonic myosin heavy chain (e-MyHC), MyHC-II and MyHC-I in regenerating
muscles. Although BGP-15 did not alter voltage dependent anion-selective channel
2 (VDAC2) expression in cryolesioned muscles, it was able to increase inducible
70-kDa heat shock protein (HSP70) expression. Our results suggest that BGP-15
improves strength recovery in regenerating soleus muscles by accelerating the re
expression of adult MyHC-II and MyHC-I isoforms and HSP70 induction. The
beneficial effects of BGP-15 on the contractile function of regenerating muscles
reinforce the potential of this molecule to be used as a therapeutic agent.
PMID- 29948664
TI - Physiological and biochemical characteristics of skeletal muscles in sedentary
and active rats.
AB - Laboratory rats are sedentary if housed in conditions where activity is limited.
Changes in muscle characteristics with chronic inactivity were investigated by
comparing sedentary rats with rats undertaking voluntary wheel running for either
6 or 12 weeks. EDL (type II fibers) and soleus (SOL) muscles (predominantly type
I fibers) were examined. When measured within 1-2 h post-running, calcium
sensitivity of the contractile apparatus was increased, but only in type II
fibers. This increase disappeared when fibers were treated with DTT, indicative
of oxidative regulation of the contractile apparatus, and was absent in fibers
from rats that had ceased running 24 h prior to experiments. Specific force
production was ~ 10 to 25% lower in muscle fibers of sedentary compared to active
rats, and excitability of skinned fibers was decreased. Muscle glycogen content
was ~ 30% lower and glycogen synthase content ~ 50% higher in SOL of sedentary
rats, and in EDL glycogenin was 30% lower. Na+, K+-ATPase alpha1 subunit density
was ~ 20% lower in both EDL and SOL in sedentary rats, and GAPDH content in SOL ~
35% higher. There were no changes in content of the calcium handling proteins
calsequestrin and SERCA, but the content of CSQ-like protein was increased in
active rats (by ~ 20% in EDL and 60% in SOL). These findings show that voluntary
exercise elicits an acute oxidation-induced increase in Ca2+ sensitivity in type
II fibers, and also that there are substantial changes in skeletal muscle
characteristics and biochemical processes in sedentary rats.
PMID- 29948665
TI - In response: Blood CO2 exchange monitoring, Haldane effect and other calculations
in sepsis and critical illness.
PMID- 29948666
TI - Comparison of conventional fluid management with PVI-based goal-directed fluid
management in elective colorectal surgery.
AB - Intraoperative fluid management is quite important in terms of postoperative
organ perfusion and complications. Different fluid management protocols are in
use for this purpose. Our primary goal was to compare the effects of conventional
fluid management (CFM) with the Pleth Variability Index (PVI) guided goal
directed fluid management (GDFM) protocols on the amount of crystalloids
administered, blood lactate, and serum creatinine levels during the
intraoperative period. The length of hospital stay was our secondary goal.
Seventy ASA I-II elective colorectal surgery patients were randomly assigned to
CFM or GDFM for fluid management. The hemodynamic data and the data obtained from
ABG were recorded at the end of induction and during the follow-up period at 1 h
intervals. In the preoperative period and at 24 h postoperatively, blood samples
were taken for the measurement of hemoglobin, Na, K, Cl, serum creatinine,
albumin and blood lactate. In the first 24 h after surgery, oliguria and the time
of first bowel movement were recorded. Length of hospital stay was also recorded.
Intraoperative crystalloid administration and urine output were statistically
significantly higher in CFM group (p < 0.001, p: 0.018). The end-surgery fluid
balance was significantly lower in Group GDFM. Preoperative and postoperative Na,
K, Cl, serum albumin, serum creatinine, lactate and hemoglobin values were
similar between the groups. The time to passage of stool was significantly short
in Group-GDFM compared to Group-CFM (p = 0.016). The length of hospital stay was
found to be similar in both group. PVI-guided GDFM might be an alternative to CFM
in ASA I-II patients undergoing elective colorectal surgery. However, further
studies need to be carried out to search the efficiency and safety of PVI.
PMID- 29948667
TI - Cardiac output and stroke volume variation measured by the pulse wave transit
time method: a comparison with an arterial pressure-based cardiac output system.
AB - Hemodynamic monitoring is mandatory for perioperative management of cardiac
surgery. Recently, the estimated continuous cardiac output (esCCO) system, which
can monitor cardiac output (CO) non-invasively based on pulse wave transit time,
has been developed. Patients who underwent cardiovascular surgeries with
hemodynamics monitoring using arterial pressure-based CO (APCO) were eligible for
this study. Hemodynamic monitoring using esCCO and APCO was initiated immediately
after intensive care unit admission. CO values measured using esCCO and APCO were
collected every 6 h, and stroke volume variation (SVV) data were obtained every
hour while patients were mechanically ventilated. Correlation and Bland-Altman
analyses were used to compare APCO and esCCO. Welch's analysis of variance, and
four-quadrant plot and polar plot analyses were performed to evaluate the effect
of time course, and the trending ability. A p-value < 0.05 was considered
statistically significant. Twenty-one patients were included in this study, and
143 and 146 datasets for CO and SVV measurement were analyzed. Regarding CO, the
correlation analysis showed that APCO and esCCO were significantly correlated (r
= 0.62), and the bias +/- precision and percentage error were 0.14 +/- 1.94
(L/min) and 69%, respectively. The correlation coefficient, bias +/- precision,
and percentage error for SVV evaluation were 0.4, - 3.79 +/- 5.08, and 99%,
respectively. The time course had no effects on the biases between CO and SVV.
Concordance rates were 80.3 and 75.7% respectively. While CO measurement with
esCCO can be a reliable monitor after cardiovascular surgeries, SVV measurement
with esCCO may require further improvement.
PMID- 29948668
TI - The breast milk lead levels among Chinese population.
AB - Breast milk is a potential source of infant and young children lead exposure, but
national-level data on breast milk lead (BML) is unknown in China. To fill up
this gap, we conducted a review by analyzing the articles enrolled through
searching Wanfang MedOnline, CNKI, SinoMed, Pubmed, and Embase databases and
relevant articles from 2000 through 2017. After screening and assessing process,
17 articles were included. The average concentrations of BML in these studies
varied with regions (1.54-171.84 MUg/L), and the BML level was dropping down in
general. In conclusion, breast milk should still be encouraged to infant and
young children in normal areas of China, and stopping breastfeeding should be
considered prudently. Education for health workers and families on BML should be
strengthened, and more surveys on BML should be conducted.
PMID- 29948669
TI - Combining micelle-clay sorption to solar photo-Fenton processes for domestic
wastewater treatment.
AB - A tertiary treatment of effluent from a biological domestic wastewater treatment
plant was tested by combining filtration and solar photocatalysis. Adsorption was
carried out by a sequence of two column filters, the first one filled with
granular activated carbon (GAC) and the second one with granulated nano-composite
of micelle-montmorillonite mixed with sand (20:100, w/w). The applied solar
advanced oxidation process was homogeneous photo-Fenton photocatalysis using
peroxymonosulfate (PMS) as oxidant agent. This combination of simple, robust, and
low-cost technologies aimed to ensure water disinfection and emerging
contaminants (ECs, mainly pharmaceuticals) removal. The filtration step showed
good performances in removing dissolved organic matter and practically removing
all bacteria such as Escherichia coli and Enterococcus faecalis from the
secondary treated water. Solar advanced oxidation processes were efficient in
elimination of trace levels of ECs. The final effluent presented an improved
sanitary level with acceptable chemical and biological characteristics for
irrigation.
PMID- 29948671
TI - Potentially toxic elements to maize in agricultural soils-microbial approach of
rhizospheric and bulk soils and phytoaccumulation.
AB - Maize fields near Mae Tao Creek in Pha Te Village, Tak Province, Thailand are
contaminated with Zn, Cd, and Pb. This research studied the interaction between
levels of the metals contaminating the soil and maize development, heavy metal
accumulation in the seeds, and the soil bacterial community structure. Our field
experiment was carried out in five plots with metal contents that gradually
decreased from a high level near the creek to a lower level further into the
land: Zn 380-4883 mg kg-1, Cd 6-85 mg kg-1, and Pb 34-154 mg kg-1. Cultivation
and isolation on nutrient agar (NA) was utilized to study the culturable
bacterial community, and polymerase chain reaction denaturing gradient gel
electrophoresis (PCR-DGGE) was utilized for the unculturable bacterial
communities. All statistical analyses clearly indicated that rainfall and
irrigation were the main factors affecting total Zn concentration and
bioavailable Zn, Cd, and Pb in the field. The variation in the contents of the
heavy metals was weakly correlated with the culturable bacterial community
indices (Shannon-Wiener, evenness and richness), but the contents resulted in a
difference in the overall diversity of the bacteria in the soil. The richness,
numbers of culturable rhizobacteria, and maize growth stage significantly
affected the amount of Zn and Cd that accumulated in the roots. In addition,
maize accumulated a high level of Zn in the seeds, while the low contents of Cd
and Pb in the seeds were below our limit of detection. The results obtained could
be informative for the management of maize cultivation in the area.
PMID- 29948672
TI - Can we use Cd-contaminated macrophytes for biogas production?
AB - Aside from the ability of plants to remove domestic-industrial wastewater
contaminants from various types of water, macrophytes can also serve as an
alternative source of energy. The goal of the present study was to test the
viability of biogas production using aquatic macrophyte species-Eichhornia
crassipes and Pistia stratiotes-contaminated with cadmium (Cd) after the
phytoremediation process. The plants were transferred to a nutrient solution
contaminated with 0.8 mg L-1of Cd. The experiment was set up in a 2 * 3 factorial
scheme with the presence or absence of Cd and three phytoremediation times (20,
40, or 60 days) using P. stratiotes followed by an additional treatment
consisting of P. stratiotes + E. crassipes for 20 days. The acute and chronic
effects of bioassays with the microcrustacean Daphnia similis were used to
evaluate the ability of the macrophytes to remove toxicity by phytoremediation.
The viability test of biogas production after phytoremediation was evaluated
using micro-biodigesters. According to the results, at least 60 days of
phytoremediation are necessary to remove/remediate the Cd present in the
contaminated solution. The metal did not influence the macrophytes' methanogenic
activity, showing that these macrophytes can be used for biogas/methane
production. The combination of Pistia stratiotes with Eichhornia crassipes is a
good alternative to reduce phytoremediation time, but for 20 days of testing, the
presence of Eichhornia crassipes reduces the biogas production/CH4. However, it
is believed that if the digestion time is extended, this effect can be minimized.
The phytoremediation time indicated that Pistia stratiotes must remain at least
60 days to remove/remediate the Cd present in the contaminated solution.
PMID- 29948670
TI - Arsenic-induced oxidative stress, cholinesterase activity in the brain of Swiss
albino mice, and its amelioration by antioxidants Vitamin E and Coenzyme Q10.
AB - Arsenic toxicity becomes one of the major public health issues in several
countries. Chronic and acute exposure to arsenic has been reported to be toxic to
various systems of the human body and also observed in controlled experimental
studies. The study was conducted to evaluate the neurotoxic effect of arsenic in
Swiss albino mice and its amelioration by Vitamin E, Coenzyme Q10 and their
combination. Swiss albino mice were treated with arsenic of 136 ppm for 15 days.
The daily dose is 1/3 of LD 50 (acute) reported dose of arsenic. Thereafter, the
animals were maintained either on drinking water or treated with Vitamin E (50
mg/kg bwt), Coenzyme Q10 (10 mg/kg bwt), and their combination by i.p.daily for
15 days. After the treatment, animals were sacrificed. The weight of the brain
was marginally lower (ns), in arsenic-treated group as compared to control and
antioxidant-protected groups. The LPO (lipid peroxidation) level was higher in
arsenic-treated group, and this elevation was checked to some extent by the
selected antioxidants which were statistically significant in combination of
antioxidant-protected group. A significant reduction was found in GSH (reduced
glutathione) level in the brain of arsenic-treated mice whereas GSH level was
considerably higher in antioxidant-protected groups. Further, total thiol and
total protein level were lower in arsenic-treated group. However, total thiol was
significantly higher in antioxidant-protected groups. CAT (catalase) activity was
significantly lower while SOD (superoxide dismutase) activity was marginally
lowered in arsenic-treated group, and it was slightly higher in antioxidant
protected groups. Further, reduction in AChE (acetylcholinesterase) and BChE
(butyrylcholinesterase) and motor coordination activity were also observed in
arsenic-treated groups. Whereas, a higher AChE, BChE, and motor coordination
activity was observed in antioxidant-protected group. These data indicate a
positive role of selected antioxidant against the toxicity of arsenic in the
brain of mice.
PMID- 29948673
TI - Water content of limestones submitted to realistic wet deposition: a CIME2
chamber simulation.
AB - An experimental chamber (CIME2) has been specially designed to simulate wet
atmospheric deposition on limestones used in Paris cultural heritage. This
instrument is a complementary tool to CIME, a previously developed chamber
dedicated to the simulation of dry atmospheric deposition on monuments and
artifacts. The aim of this paper is to describe CIME2 and characterize the wet
deposits produced inside it. Mist (fog), drizzle, and rainfall are differentiated
in order to document their ability to saturate the limestones most currently used
in Paris monuments: The Saint-Maximin's limestone, the Liais of Saint-Maximin,
and the Chauvigny's limestone are tested. The comparison between normalized and
environmental petrophysical data shows that in the wet deposition simulations,
limestones are not systematically water-saturated. Moreover, the realistic
experimental conditions chosen favor a more rapid evaporation of the stone water.
The quantification of the non-saturation state is a first step that has to be
taken into account to improve the geochemical models used to predict the
alteration.
PMID- 29948674
TI - Persistence of picloram in soil with different vegetation managements.
AB - Herbicides with long residual period may increase the risk of environmental
contamination. Adequate management of forage can reduce the half-life of the
picloram, one of the most herbicides used in weed control. This study aims to
determine the half-life of picloram, using high-performance liquid chromatography
in a cultivated soil with Brachiaria brizantha trimmed or not. Brachiaria
brizantha was cultivated in 60 pots filled with samples of oxisol, and 30 others
were kept uncultivated with this forage. This plant was cut off close to the
ground, after 60 days of emergency on 30 vessels. Picloram was applied in all of
the plots. Soil samples were collected at 2, 16, 30, 44, 58, 72, 86, 120, 150,
and 180 days after the application of this herbicide. These samples were air
dried and stored at - 20 degrees C. Picloram was extracted by HPLC/UV-Vis
detector. Half-life of this herbicide was calculated using kinetics models. The
mere presence of roots in treatment with signalgrass cutoff did not reduce the
concentrations of this herbicide, except when the emergence of new leaves
occurred. The absence of B. brizantha cultivation in areas with application of
picloram increases the risk of environmental contamination and successive crops
due to the half-life of this herbicide. Brachiaria brizantha reduced half-life
picloram and environmental risk in pastures. The validation method is suitable
for determining picloram in low concentrations in soil.
PMID- 29948675
TI - Humic substances in Fluvisols of the Lower Vistula floodplain, North Poland.
AB - The present study describes properties of humic substances of the Fluvisols (the
Lower Vistula, Poland). Fluvisols under agricultural management (arable soil and
grassland) were sampled from the surface horizon 50, 200, 600, and 900 m from the
Vistula River. The content of carbon in the fractions of humic acids (CHAs),
fulvic acids (CFAs), and humins (CHUMIN) as well as the content of dissolved
organic carbon (DOC) were assayed. The organic matter of the soils that were
sampled 200 m from the river demonstrated a lowest share of the humic acids (HAs)
and fulvic acids (FAs). The percentage share of the hydrophilic fractions (HIL)
in the HAs and, as a result the value of the HIL/SigmaHOB ratio, increased with
the distance from the riverbed. The HAs of the soils located further from the
riverbed had a higher degree of humification compared to the HAs of the soils
that were sampled 50 and 200 m away. Based on the research results, it was
determined that the properties of HAs can be used to evaluate the effect of flood
events, their location, and scope on the transformation of the organic matter in
fluvial sediments.
PMID- 29948676
TI - Occurrence and ecological risk assessment of 22 emerging contaminants in the
Jilin Songhua River (Northeast China).
AB - Rivers may receive pharmaceuticals, personal care products, and environment
estrogens, which are emerging concerns, from various sources. Understanding the
fate of these emerging contaminants (ECs) from the sources to their receiving
river is important for assessing their ecosystem risk. Here, the occurrence,
seasonal variation, spatial distribution, and ecological risk of 22 ECs in water
and sediments from the Jilin Songhua River, as well as in the effluents from the
riverside Jilin wastewater treatment plant (WWTP) were investigated. Results
indicated that estriol with the highest median concentration of 21.5 ng L-1 in
the river water and with the highest median concentration of 481.5 ng g-1 in the
sediments, and methylparaben with the highest concentration of 29.6 +/- 2.9 ng L
1 in the WWTP effluents were the predominant contaminants. The total
concentration of ECs in the river water in the dry season was about 1.5 times
higher than that in the wet season. The concentrations of these ECs close to the
contaminated tributary and the WWTP were relatively high. Risk assessment showed
that the maximum risk quotient value of estrone was 1.07 in the river water and
estriol was 2.10 in the effluents. In addition, erythromycin posed generally
medium risk in the river water and WWTP effluents. It should be paid attention to
the prior control of the three contaminants in the river region.
PMID- 29948677
TI - The dependency analysis between energy consumption, sanitation, forest area,
financial development, and greenhouse gas: a continent-wise comparison of lower
middle-income countries.
AB - This study explored the long-run association among greenhouse gases (GHGs),
financial development, forest area, improved sanitation, renewable energy,
urbanization, and trade in 24 lower middle-income countries from Asia, Europe,
Africa, and America (South and North) by using panel data from 1990 to 2015.
Granger causality was tested by Toda and Yamamoto approach. The bi-directional
causality was established among urbanization and GHGs (Asia), financial
development and forest (Asia), energy use and renewable energy (Asia), renewable
energy and forest (Asia), improved sanitation and forest (Asia, Africa, America),
urbanization and forest (Asia), and improved sanitation and financial development
(Europe). The GHG emission also shows one-way causality is running from financial
development to GHG (America), energy to GHG (Asia), renewable energy to GHG
(America), forest area to GHG (America), trade openness to GHG (Africa),
urbanization to GHG (Europe), GHG to financial development (Europe), GHG to
energy use (Europe, Africa, and America), and GHG to trade openness (Asia). On
the basis of fully modified ordinary least square and generalized method of
moment, the reciprocal relationship of GHGs was observed due to financial
development in Asia and Africa; renewable energy in all panels; forest area in
Asia, Europe, and America; improved sanitation in Asia, Africa, and America;
trade openness in Africa; and urbanization in Europe and America. Policymakers
should concentrate on these variables for the reduction in GHGs. The annual
convergence towards long-run equilibrium was 50.5, 31.9, and 20.9% for America,
Asia, and Africa, respectively.
PMID- 29948678
TI - Lycopene reduces in utero bisphenol A exposure-induced mortality, benefits
hormones, and development of reproductive organs in offspring mice.
AB - This study was conducted to investigate the protective effect of lycopene on
reproductive toxicity induced by in utero exposure to bisphenol A (BPA) in
offspring mice. Pregnant mice in the BPA model group were given orally 500
mg/kg/day BPA from pregnant day (PD)8 to PD14. Mice of lycopene group were
gavaged with 20 mg/kg/day lycopene from PD1 to PD7 and then given 500 mg/kg/day
BPA from PD8 to PD14. Results showed that lycopene reduced the elevated mortality
in offspring mice of the mother exposed to BPA. BPA lowered the levels of
testosterone, luteinizing hormone, and follicle-stimulating hormone while
lycopene treatment increased the levels significantly. BPA elevated estradiol
while lycopene lowered estradiol in the offspring. BPA caused testicular damage
as shown by less Leydig cells and ovarian injury as shown by less corpus granules
in adult offspring, while lycopene decreased the damages. Maternal exposure to
BPA increased Bax and decreased Bcl-2 in testicular and ovary tissues in the
offspring mice. Lycopene decreased Bax in testis and ovary and increased Bcl-2 in
ovary tissues in the offspring mice. These findings suggest lycopene has
protective effects on in utero BPA exposure-induced reproductive toxicity in
offspring mice.
PMID- 29948679
TI - Seasonal variation and source analysis of persistent organic pollutants in the
atmosphere over the western Tibetan Plateau.
AB - Over the past few decades, the Tibetan Plateau (TP) region has become gradually
contaminated by persistent organic pollutants (POPs). The picture regarding POPs
is clear in the central and southern parts of the TP; however, few observational
campaigns have focused on the western TP. To clarify the concentrations, seasonal
trends and source regions of POPs in the western TP, a first study of POPs in
Muztagh Ata (westerly region) and a long-term (5 years) monitoring program in
Ngari (transect region influenced by both the Indian monsoon and westerly
climate) were conducted. Except for hexachlorobenzene (HCB) and polychlorinated
biphenyls (PCBs), relatively low POP levels were observed in the western TP. In
Muztagh Ata, dichlorodiphenyltrichloroethanes (DDTs) showed higher concentrations
in winter and lower ones in summer, whereas at Ngari, higher DDTs and
hexachlorocyclohexanes (HCHs) concentrations were observed in summer as compared
with winter. Source diagnosis indicated that Xinjiang and central Asia were the
main source regions for POPs in Muztagh Ata and that westerly winds play a key
role in transporting POPs from central Asia. No correlation was found between the
height of the atmospheric boundary layer and the concentrations of POPs over the
TP.
PMID- 29948680
TI - Occurrence of tumors among gastropods Plicopurpura pansa (Gastropoda:
Neogastropoda) in the Port of Manzanillo, Mexico.
AB - In order to evaluate the health of Plicopurpura pansa, a species considered
vulnerable, a population of this gastropod living in proximity to the port of
greatest cargo movement in Mexico was monitored seasonally during 1 year.
Morphometric characteristics and sexual proportion were recorded. A macroscopic
analysis was carried out to detect malformations and imposex; a histological
analysis was performed to evaluate disseminated and gonadal neoplasias; the
presence/absence in soft tissues of butyltin species (BTs) as possible
contamination agents was also estimated. A total of 508 P. pansa specimens were
collected. The largest specimens were obtained in winter. The coefficients of
determination inside the port were low (R2 = 0.453). In general, there was a
greater proportion of females than males throughout the year. Distinctive foot
malformations (tumors) were recorded, but without signs of imposex. The
histological examination confirmed the presence of disseminated neoplasias in the
foot and gonads of P. pansa in the Port of Manzanillo. The comparative analysis
of the morphological and histological features of the studied gastropod
population allowed us to recognize impact patterns in relation to proximity to
the port. There were high concentrations of monobutyltin (MBT) and greater
abundance of tumors in heavier specimens; this was associated with port proximity
zones. P. pansa could therefore serve as a sensitive bioindicator of
environmental health in marine systems.
PMID- 29948681
TI - Characterisation of "flushable" and "non-flushable" commercial wet wipes using
microRaman, FTIR spectroscopy and fluorescence microscopy: to flush or not to
flush.
AB - The introduction to the market of wet wipes, advertised and labelled as
"flushable", has been the subject of controversy due to their perceived potential
to block sewer systems as observed with other non-woven cloths such as
traditional non-flushable wipes. Non-woven cloths that enter wastewater systems
can find their way into the aquatic environment via wastewater effluents and it
has been suggested that the breakdown of these fabrics can release materials such
as microplastics into the environment. Worldwide research has revealed the
alarming number of aquatic organisms affected by the presence of plastic debris
in the aquatic environment harbouring a potential risk to humans through the
introduction of microplastics into the food chains. However, the actual material
composition of flushable wipes, their fate and impacts in the aquatic environment
have not yet been scientifically studied. This paper investigates the fibre
composition of flushable and non-flushable wipes, specifically with regard to
synthetic polymer material, using Fourier transform infrared (FTIR) and
microRaman spectroscopy along with fluorescence microscopy. The study
demonstrated the presence of polyester (polyethylene terephthalate, (PET)), high
density polyethylene (HDPE) and polyethylene/vinyl acetate (PEVA/EVA) in some
flushable wipes and PET in all non-flushable. Other polymers such us
polypropylene (PP), low-density polyethylene (LDPE), expanded polystyrene (EPS)
and polyurethane (PU) were also identified as potential components in the
flushable material. Hence, commercially available wet wipes labelled as flushable
could also be considered as a possible source of microplastic fibres in the
wastewater streams and, if not retained, in the environment.
PMID- 29948682
TI - A comparative analysis for the development and recovery processes of different
types of clogging in lab-scale vertical flow constructed wetlands.
AB - Clogging is a major operational and maintenance issue associated with the use of
constructed wetlands. In this study, four lab-scale vertical flow constructed
wetlands (VFCW) were used to fully understand the development mechanisms of
various types of clogging and their recovery characteristics. The VFCWs were fed
with glucose solution, starch suspension with and without bacteriostat, glucose,
and starch mixed solution, respectively, to simulate Bio-clogging, organic
particle clogging (Op-clogging), inert particle clogging (Ip-clogging), and the
combination of Bio-clogging and Op-clogging (C-clogging). Resting operations with
water decline were applied to relieve the clogging in the VFCWs. The results
indicate that Op-clogging occurred first, followed by C-clogging and Bio
clogging. Ip-clogging took the longest time to develop and did not occur by the
end of this study. The microscope analysis found that the extracellular polymeric
substances (EPS) bonded the starch particles together to form a dense membrane
like structure and promoted the clogging process. In addition, surface clogging
was observed in all four experimental beds. Op-clogging occurred much closer to
the surface than those caused by soluble organic matter and inert particles.
Furthermore, the growth of biofilm caused significant decline in hydraulic
conductivity, whereas its influence on porosity was relatively slight. Moreover,
applying resting operation with water decline was effective for recovery from Bio
clogging, Op-clogging, and C-clogging in VFCWs except for Ip-clogging. The
results also implied the recovery rates through applying resting operation with
water decline were much higher than that with constant water level.
PMID- 29948683
TI - Occurrence, removal and environmental risk of markers of five drugs of abuse in
urban wastewater systems in South Australia.
AB - The occurrence and fate of five drugs of abuse in raw influent and treated
effluent wastewater were investigated over a period of 1 year in the Adelaide
region of South Australia. Four wastewater treatment plants were chosen for this
study and monitored for five drugs which included cocaine in the form of its
metabolite benzoylecgonine (BE), methamphetamine, 3,4
methylenedioxymethamphetamine (MDMA) and two opioids (codeine and morphine)
during the period April 2016 to February 2017. Alongside concentrations in raw
sewage, the levels of drugs in the treated effluent were assessed and removal
efficiencies were calculated. Drug concentrations were measured by mixed-mode
solid phase extraction and liquid chromatography coupled to a quadrupole mass
spectrometer. Drug concentrations detected in the raw wastewater ranged from 7 to
6510 ng/L and < LOD to 4264 ng/L in treated effluent samples. Drug removal rates
varied seasonally and spatially. The mass loads of drugs discharged into the
environment were in descending order: codeine > methamphetamine > morphine > MDMA
> BE. Results showed that all the targeted drugs were on average incompletely
removed by wastewater treatment, with removal performance highest for morphine
(94%) and lowest for MDMA (58%). A screening-level environmental risk assessment
was subsequently performed for the drugs based on effluent wastewater
concentrations. Based on calculated risk quotients, overall environmental risk
for these compounds appears low, with codeine and methamphetamine likely to pose
the greatest potential risk to receiving environments. Given the recognised
limitations of current ecotoxicological models and risk assessment methods for
these and other pharmaceutical drugs, the potential for environmental impacts
associated with the continuous discharge of these compounds in wastewater
effluents should not be overlooked.
PMID- 29948684
TI - Biomonitoring birds: the use of a micronuclei test as a tool to assess
environmental pollutants on coffee farms in southeast Brazil.
AB - Birds have often played an important role as environmental bioindicators, and
different species can be useful due to their bioaccumulating capacity. The
micronuclei test is a cytologic technique used for accessing DNA and is a
biomarker for damage to DNA. This study analysed the Cerrado avian community,
especially the efficiency of the blue-black grassquit (Volatinia jacarina) in
responding to pesticide contamination in situ on different-sized coffee farms in
southeast Brazil. The micronuclei test was used in erythrocytes of birds. Eighty
two individuals of 21 bird species belonging to 11 families that were found in
all study areas were used to evaluate micronuclei (MN) frequency. Two hundred
fifty-two MN were counted in every area of study. The MN average count was
3/10,000 erythrocytes, and 17.1% of all bird species exhibited no MN. The average
MN was 1.29 +/- 0.69 in small farms, 2.59 +/- 1.65 in medium farms, and 5.41 +/-
1.34 in large farms. Small farms accounted for 14.3% of MN frequency, medium
farms 27.8%, and large farms 57.9%. V. jacarina was the most abundant species
found and displayed a sensitive response to environmental contamination.
Pesticides appear to induce MN formation in a dose-dependent way when farms are
analysed according to their area. Therefore, biomonitoring birds remain an
efficient means to detect environmental pollutants, especially pesticides. V.
jacarina responds as a sensitive biomonitor, showing a dose-dependent response to
pesticides used in coffee farms.
PMID- 29948685
TI - Effects of soil improvement technology on soil quality in solar greenhouse.
AB - Currently, cucumber cultivation is mainly through monoculture, as continuous
culture leads to the decrease of crop yield and soil quality. In order to improve
soil quality to achieve continuous monocultures, soil physicochemical properties,
microbial biomass, content of phenolic compounds, and the size of bacterial,
fungal, ammonia-oxidizing bacteria (AOB), and Fusarium oxysporum were first
evaluated in cucumber monoculture solar greenhouse. Soil improvement technology,
including catch wheat (CW), calcium cyanamide disinfection (LN), and straw
reactor technology (SR) during summer fallow period, was compared with
conventional fallow (CK). Results showed that CW, LN, and SR all significantly
increased soil pH, and LN and SR increased soil electrical conductivity (EC);
however, CW decreased soil EC. Meanwhile, LN increased soil available N content
significantly and SR increased available P content significantly. CW had negative
effect on the accumulation of soil available nutrients, conversely, CW and SR had
positive effect on the accumulation of microbial biomass carbon (MBC). All the
treatments increased the total phenol content in the soil compared with CK. While
CW increased the size of bacteria, AOB in the soil inhibited fungal and wilt
pathogen size. LN also increased the size of soil bacteria and reduced the size
of fungi. The comprehensive evaluation of all treatments showed that CW could
control soil nutrient loss and improve the continuous cropping soil, making the
soil transform from fungi to bacteria type. All the treatments accelerate the
accumulation of phenolic compound, while whether or not developing autotoxicity
requires further investigation.
PMID- 29948686
TI - Plant species diversity for vegetation restoration in manganese tailing
wasteland.
AB - Vegetation restoration is one of the most effective measures to restore degraded
ecosystem in mining wasteland. A field experiment was conducted to study the
effects of some site treatments' three different approaches on the benefits of
selective vegetation in the manganese mine. Three different approaches included
(1) exposed tailings, the control treatment (tailing site); (2) soil covering of
10-cm thickness (external-soil site), and (3) soil covering of 10-cm thickness,
soil ameliorating (adding fowl dung), and seeding propagation of Cynodon dactylon
(Linn.) Pers. (rehabilitation site). The results indicated that 18 herb species
were taken from 8 families and 4 woody plants in three sites after 1 year. After
3 years, 29 species from 14 families were observed in 3 sites. Meanwhile,
compared with tailing site, the plant species of rehabilitation site was more
than tailing site, and the plant abundance of external-soil site was similar to
rehabilitation site. It was worthy to be mentioned that the plant species of
external-soil site and rehabilitation site had a better effect on the plant
community coverage of herb layer as compared with tailing site. In summary, the
plant species of rehabilitation site had the most species diversity and could be
recommended as the ve-restoration modes in manganese tail wasteland.
PMID- 29948687
TI - Role of organic fouling layer on the rejection of trace organic solutes by
nanofiltration: mechanisms and implications.
AB - To investigate how the organic fouling layers on nanofiltration (NF) membrane
surface and the strong matrix effect (particularly by Ca2+) influence the
rejection of trace organic compounds (TOrCs), filtration experiments with two
TOrCs, bisphenol A (BPA) and sulfamethazine (SMT), were carried out with virgin
and organic-fouled NF membrane. Organic fouling layer on the membrane was induced
by sodium alginate (SA) at different concentrations of Ca2+. The results
indicated that NF membrane maintained consistently rejection of TOrCs with little
influence by membrane fouling at lower Ca2+ concentration. In contrast, organic
fouling caused at higher concentration of Ca2+ observably restrained the
rejections of both BPA and SMT. Furthermore, based on the cake-enhanced
concentration polarization (CECP) model, the rejection of TOrCs was divided to
the real rejection and the mass transfer coefficient. Moreover, it was found that
the decrease in rejection resulted by organic fouling was due to the real
rejection that was restrained by fouling layer with irregular impact on the mass
transfer coefficient. Although the mechanism of trace compounds rejection was
complex, the controlling factors varied among foulants. Nevertheless, the steric
effect of the cake layer played an important role in determining solute rejection
by organic-fouled NF membrane.
PMID- 29948689
TI - Application of direct contact membrane distillation for saline dairy effluent
treatment: performance and fouling analysis.
AB - Membrane distillation is getting increasing attention thanks to its advantages in
terms of energy consumption and final permeate quality in addition to its
resistance against highly corrosive media which forms an appealing solution for
industrial wastewater treatment. Despite its advantages, one of the most
challenging issues in direct contact membrane distillation (DCMD) is membrane
fouling and wetting. In the present research work, saline dairy effluent
discharged from hard cheese industry was pretreated by macrofiltration (MAF) and
ultrafiltration (UF) and processed by DCMD to investigate the extent of the
aforementioned issues. Effluents pretreated by UF have led the best process
performance with stable flux values at different operating conditions. Fouling
has occurred in all the experiments, though their effect on the flux behavior and
membrane wetting was different from one feed to the other. Changing the flow rate
and the temperature difference have affected slightly the membrane wettability
for all feed qualities. In all experiments, the permeate has maintained a good
quality with low electrical conductivity that did not exceed 70 MUS/cm and low
total organic carbon < 2 mg/L.
PMID- 29948688
TI - Phytoavailability, bioaccumulation, and human health risks of metal(loid)
elements in an agroecosystem near a lead-zinc mine.
AB - Soil near a Pb-Zn-Mn mine was polluted by mining, which may have an impact on
human health via the food chain. To evaluate the pollution effects, arsenic (As),
cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), lead (Pb), and zinc
(Zn) in vegetables were determined by inductively coupled plasma atomic emission
and mass spectrometry. Lead species were analyzed by X-ray absorption near-edge
structure (XANES). Phytoavailability of the elements was evaluated by
bioaccumulation of the elements, the sequential extraction procedure, Pb species,
and plant uptakes. The target health quotient (THQ) was calculated to evaluate
the human health risks. It was found that (1) high concentrations of As, Cd, Cr,
and Pb were detectable in vegetables, and bioaccumulation was in the order of Mn
> Zn > Cr > Pb > Cu > As > Cd; (2) phytoavailability of the elements was
controlled mainly by the soluble fraction, and a linear relationship observed
between the soluble fraction and bioaccumulation; (3) a new Pb-fulvic acid
complex (Pb-FA) was identified by XANES in rhizosphere soil, and high content of
Pb organic matter (60%) and soluble Pb (18%) were found; (4) both Cd and Zn
accumulated in both of the Amaranthaceae and the Apiaceae families, indicating
that the plants in the same family have the same bioaccumulation trend for the
elements in the same group; (5) agricultural activities and plant growing
increased phytoavailability of As, Cd, Cu, Pb, and Zn by decreasing the residual
and raising the soluble and extractable fractions; (6) arsenic is top of the high
health risks, followed by Pb, Cd, and Mn. Coriander, celery, and spinach were the
top three highest health risks in the area.
PMID- 29948690
TI - Photodegradation of cyclohexane and toluene using TiO2/UV/O3 in gas phase.
AB - Volatile organic compounds (VOC) are air pollutants usually found in urban and
industrial areas. Heterogeneous photocatalysis is an interesting technique used
to degrade these compounds. Several approaches may enhance this process; some
studies have shown higher VOC conversions by adding ozone to the experimental
system, once ozone increases the number of reactive radicals in the reaction. In
this context, this work studied the conversion of cyclohexane and toluene by
heterogeneous photocatalysis in gas phase, in the presence of titanium dioxide
(TiO2), UV light, and different concentrations of ozone. For fixed space times
from 13.1 to 48.8 s, an average increase of 9% was reached in cyclohexane
conversion when comparing the system with maximum concentration of ozone (0.8%)
and the system without it. In addition, difference of less than 2% in the
conversion of cyclohexane with different moisture fractions was observed. Toluene
photodegradation was also analyzed in the presence of ozone and although the
conversion was only about 40% for the space time of 25 s, this result was
maintained during 4 h of experiment, with no catalyst deactivation as usually
reported in the literature for aromatic compounds. Based on the results, ozone
addition is an advantageous technique to improve the photodegradation of VOC.
PMID- 29948691
TI - Reduced arsenic availability and plant uptake and improved soil microbial
diversity through combined addition of ferrihydrite and Trichoderma asperellum SM
12F1.
AB - Arsenic (As) accumulation in agricultural soils is prone to crop uptake, posing
risk to human health. Passivation shows potential to inactivate soil labile As
and lower crop As uptake but often contributes little to improving the microbiota
in As-contaminated soils. Here, the combined addition of ferrihydrite and
Trichoderma asperellum SM-12F1 as a potential future application for remediation
of As-contaminated soil was studied via pot experiments. The results indicated
that, compared with the control treatment, the combined addition of ferrihydrite
and T. asperellum SM-12F1 significantly increased water spinach shoot and root
biomass by 134 and 138%, respectively, and lowered As content in shoot and root
by 37 and 34%, respectively. Soil available As decreased by 40% after the
combined addition. The variances in soil pH and As fractionation and speciation
were responsible for the changes in soil As availability. Importantly, the
combined addition greatly increased the total phospholipid fatty acids (PLFAs)
and gram-positive (G+), gram-negative (G-), actinobacterial, bacterial, fungal
PLFAs by 114, 68, 276, 292, 133, and 626%, respectively, compared with the
control treatment. Correspondingly, the soil enzyme activities closely associated
with carbon, nitrogen, and phosphorus mineralization and antioxidant activity
were improved. The combination of ferrihydrite and T. asperellum SM-12F1 in soils
did not reduce their independent effects.
PMID- 29948692
TI - Low-thermal remediation of mercury-contaminated soil and cultivation of treated
soil.
AB - In this study, low-thermal technology was used to treat the mercury contaminated
farmland soil from a chemical plant in Guizhou Province, China. A series of field
planting experiments were also aimed at determining the content of total and
methyl-Hg in crop plants after thermal treatment. The results showed that the
mercury concentration in soils was reduced about 70% from 255.74 mg/kg to 80.63
mg/kg when treated at 350 degrees C for 30 min in engineering-scale experiments,
and the treated soil retained most of its original soil. Organic-bound and
residual mercury in treated soil were reduced by 64.1 and 56.4% by means of a
sequential extraction procedure, respectively. The total and methyl-mercury
concentrations in crops decreased significantly, and the degree of soil mercury
accumulation to crop roots has been reduced significantly. The total Hg
concentrations in potato and corn were lower than the mercury tolerance limits
for food in China, and the Hg concentration of radish was close to the limit. The
technology provides a more sustainable remediation method for treating mercury
contaminated farmland soil in future engineering applications.
PMID- 29948693
TI - Screening effects of metsulfuron-methyl to collembolans and earthworms: the role
of adjuvant addition on ecotoxicity.
AB - Metsulfuron-methyl is a common active ingredient recommended for use in pre- and
post-emergence control of annual grasses and broadleaf weeds in crops, usually
applied with mineral oil as adjuvant to enhance its efficiency. Despite the
increasing use of this herbicide, there are no information on its ecotoxicity
effects to soil fauna. Avoidance and lethality tests were performed with
earthworms and collembolans using tropical artificial soil contaminated with
formulated products Ally(r) (600 g L-1 metsulfuron-methyl) and Assist(r) (756 g L
1 mineral oil) as adjuvant. Lethality test with earthworms showed no difference
when tested with or without adjuvant. When Ally(r) was tested alone, it caused
avoidance behavior only at high concentrations (5000 and 10,000 times field
predicted dose). However, Assist(r) addition changed the response of soil
invertebrates increasing the avoidance even at field predicted doses. The
toxicity of the adjuvant was confirmed in tests exposing collembolans and
earthworms to Assist(r) alone resulting in avoidance behavior. The results
clearly show that the addition of mineral oil enhanced the ecotoxicity of
metsulfuron-methyl. This study provides an important contribution to the
knowledge on the toxicity of metsulfuron-methyl and indicates that adjuvants
should be considered in risk assessment of pesticides, considering that under
field conditions, these products are applied together.
PMID- 29948694
TI - Chemical composition of rainwater in the Sinos River Basin, Southern Brazil: a
source apportionment study.
AB - This study aimed to assess the chemical composition of the rainwater in three
areas of different environmental impact gradients in Southern Brazil using the
receptor model EPA Positive Matrix Factorization (EPA PMF 5.0). The samples were
collected in a bulk sampler, from October 2012 to August 2014, in three sampling
sites along with the Sinos River Basin: Caraa, Taquara, and Campo Bom. The major
ions NH4+, Na+, K+, Ca2+, Mg2+, F-, Cl-, NO3-, SO42-, and pH were analyzed, as
well as identify the main emission sources. The most abundant cations and anions
were Ca2+, Na+, Cl-, and SO42-, respectively. The mean pH value in the Sinos
River Basin during the study period was 6.07 +/- 0.49 (5.13-7.05), which suggests
inputs of alkaline species into the atmosphere. The most important neutralizing
agents of sulfuric and nitric acids in the Sinos River Basin are Ca2+ (NF = 1.36)
and NH4+ (NF = 0.57). The source apportionment provided by the EPA PMF 5.0
resulted in four factors, which demonstrate the influence of anthropogenic and
natural sources, in the form of (a) industry/combustion of fossil fuels (F- and
SO42-), (b) marine contribution (Na+ and Cl-), (c) crustal contribution (K+,
Ca2+, and NO3-), and (d) agriculture/livestock (NH4+). Therefore, this study
allows a more appropriate understanding of factors that contribute to rainwater
chemical composition and also to possible changes in air quality.
PMID- 29948695
TI - Environmental behaviors of spirotetramat in water.
AB - Spirotetramat is a pesticide with bidirectional systemicity in both xylem and
phloem. Currently, researches show that spirotetramat has definite toxicity to
aquatic organism. This paper aims to study the environmental behaviors of
spirotetramat in water, in the hope of providing guidance for security evaluation
of spirotetramat. The researches in this paper showed that under lighting
condition, the half-life period of spirotetramat in water was 13.59 days. In
water, spirotetramat could be degraded into B-enol and B-keto. As seen from the
residual concentrations of two products, B-enol was the dominant degradation
product. Under different temperatures, the hydrolysis products of spirotetramat
remain B-enol and B-keto. The temperature has little effect on the residual
concentration of spirotetramat in water. The residual concentration of B-enol in
water gradually increased with the extension of time but B-keto had no
significant change. In the buffer solution of different pH values, the
degradation rate of spirotetramat was significantly enhanced with the increase of
solution pH value. The hydrolysis products of spirotetramat in buffer solution of
different pH values were still B-enol and B-keto, and pH exerted certain
influence on the residual concentration of B-enol in water. The hydrolysis
conversion of spirotetramat has theoretical and practical significance for the
safe and reasonable usage of it, as well as for the further evaluation of
spirotetramat's ecological risk in water.
PMID- 29948696
TI - Interaction between copper and extracellular nucleic acids in the EPS of
unsaturated Pseudomonas putida CZ1 biofilm.
AB - The role of extracellular DNA (eDNA) in biofilm in heavy metal complexation has
been little reported. In this study, the interaction between the extracellular
fraction of unsaturated biofilms and Cu2+ was studied using random amplified
polymorphic DNA (RAPD) and synchrotron-based X-ray absorption spectroscopy (XAS)
analyses. Under Cu2+ stress, the amount of eDNA was about 10-fold higher than the
treatment without Cu2+ stress, which was substantially more than the amount of
intracellular DNA (iDNA) present in the biofilm. The eDNA content increased
significantly under Cu2+ stress and higher eDNA contents were found in colloidal
extracellular polymeric substances (EPS) than in capsular EPS in Luria-Bertani
medium. It was found that the composition of eDNA was distinctly changed under
conditions of Cu2+ stress compared with the treatments without Cu2+ treatments,
with specific eDNA bands appearing under Cu2+ treatments as revealed by RAPD
analyses. X-ray absorption fine structure (XAFS) analysis assessing the molecular
speciation of copper showed that copper in the secreted eDNA mainly existed as
species resembling Cu3(PO4)2, followed by Cu-citrate species. This study
investigated the interaction between copper and eDNA in unsaturated Pseudomonas
putida CZ1 biofilms. Potential function of eDNA in biofilms under Cu2+ stress was
found.
PMID- 29948697
TI - Testing biomarker feasibility: a case study of Laeonereis culveri (Nereididae,
Annelida) exposed to sewage contamination in a subtropical estuary.
AB - The feasibility of biomarkers to accurately detect pollution in estuaries and
coastal areas appears to be overestimated in the scientific literature, and is
likely stemming from a bias towards publishing only positive results. Herein, we
test the applicability of antioxidant capacity and lipid peroxidation to detect
potential in situ sewage impacts on a subtropical estuary. We experimentally
assessed variation in malondialdehyde (MDA, an indicator of lipid peroxidation)
and total antioxidant capacity against peroxyl radicals (ACAP) through
transplantations of the worm Laeonereis culveri from control to sewage-polluted
areas. Variations in biomarkers were more related to natural environmental
variability and small-scale heterogeneity among areas than to experimental
exposure to sewage. Use of oxidative stress biomarkers is promising but further
experimental work under real-life conditions is necessary to further validate and
establish their accuracy and feasibility for practical purposes.
PMID- 29948698
TI - Effect of anhydrous ethanol/gasoline blends on performance and exhaust emissions
of spark-ignited non-road engines.
AB - Ethanol is a renewable fuel and it is considered an alternative to gasoline in
Otto-cycle engines. The present study evaluated the behavior of exhaustion gas
carbon monoxide (CO) and total hydrocarbons (THC) according to the levels of
anhydrous ethyl alcohol (AEA) added to gasoline in different proportions (E0,
E10, E20, E27, that is, pure gasoline and its blends with AEA at 10, 20, and 27%
v/v) in the use of non-road single cylinder engines of different powers (13 and
6.5 hp), to the loads applied to engine-generators and the air-fuel ratio (A/F)
admitted to the engine cylinders. Also, the performance of engine-generators was
verified in terms of mass, specific and energetic consumption and efficiency of
the evaluated systems for the same blends and loads. The results showed that an
increase in the AEA content in the blend resulted in significant drops in CO and
THC concentrations for both engine-generators, while fuel consumption showed a
slight upward trend; the increases in applied loads resulted in an increase in CO
and THC concentrations and fuel consumption. In general, a higher AEA content
(oxygenated) in the blends had a greater effect on gaseous emissions compared to
the effect on consumption and system efficiency.
PMID- 29948699
TI - Emissions of selected brominated flame retardants from consumer materials: the
effects of content, temperature, and timescale.
AB - The ubiquitous presence of brominated flame retardants (BFRs) in indoor air,
dust, and even in human tissue could be attributed to their emissions from BFR
containing products. Nevertheless, the emission behavior of BFRs, especially
novel BFRs from consumer materials, to the indoor environment has still not been
well understood. To evaluate the effects of chemical content, temperature, and
time on the emissions of BFRs, we used a batch of small glass chambers to conduct
emission tests on carpet, computer casings, sound insulation, circuit boards,
decorative laminate, and PVC floors at temperatures from 20 to 80 degrees C, as
well as different emission times of up to 35 days. Seven BFRs were extracted from
the tested materials with contents ranging from 50 to 35,803 MUg g-1, and four
BFRs were detected with emission rates between 5.9 and 418 pg g-1 h-1 at room
temperature (20 degrees C); 1,2,5,6,9,10-hexabromocyclododecane (HBCD) was
considered to be the dominant compound, which was found in and could be emitted
from all of the tested materials. Emission rates are significantly and positively
correlated with both the contents of tested materials and the elevated
temperature. These results indicate that BFR-containing products have the
potential to be a major source of indoor contamination.
PMID- 29948700
TI - Green synthesis of gold nanoparticles using Artemisia dracunculus extract:
control of the shape and size by varying synthesis conditions.
AB - In this study, selective green synthesis of gold nanoparticles (nAu) with the use
of Tarragon extract (Artemisia dracunculus) was investigated. Characterization of
the synthetized nAu was carried out using several techniques including: UV-Vis,
SEM, zeta potential analysis, DLS, and ATR-FTIR. Based on measurements of
Tarragon extract by HPLC-MS, significant chemical substances participating as
reducing and stabilizing agents were identified. FTIR confirmed typical
functional groups that could be found in these acids on the nAu surface, such as
O-H, C=O and C-O. The effects of various parameters (concentration of Tarragon
extract, Au precursor, and initial pH of the synthesis) on the shape and size of
the nanoparticles have been investigated. UV-Vis and SEM confirmed the formation
of nAu at various concentrations of the extract and Au precursor and showed
correlation between the added extract concentration and shift in maximal
absorbance towards higher frequencies, indicating the formation of smaller
nanoplates. Zeta potential determined at various pH levels revealed that its
value decreased with pH, but for all experiments in the pH range of 2.8 to 5.0,
the value is below - 30 mV, an absolute value high enough for long-term nAu
stability. In order to evaluate nAu catalytic activity, the reduction of 4
nitrophenol to 4-aminophenol by sodium borohydride was used as a model system.
The reaction takes place 1.5 times faster on Au-triangles than on Au-spherical
NPs.
PMID- 29948702
TI - Socio-economic factors influencing farmers' willingness to undertake
environmental responsibility.
AB - Acknowledging the importance of water resources protection and sustainable
management, the European Parliament enacted directives based on the "polluter
pays" principle aiming for "environmental damage" protection and restoration of
water resources. The main aim of this paper is to examine, for the first time in
Greece, the possibility of achieving environmental goals, such as reduction of
agrochemical pollution and irrigation water use, alongside with the farmers'
willingness to undertake the environmental costs arising from their activity. In
a questionnaire survey, conducted using a "state preference" method, participants
were asked to respond on whether they are willing to absorb an "environmental
charge" for the protection and restoration of surface and ground water. It is an
essential precondition to understand the factors that affect taxpayers'
willingness to participate in the Water Framework Directive, as they are expected
to cover the cost of its implementation. The identification of the driving forces
that affect stakeholders' environmental decisions can emerge as an important and
useful tool in extending public participation in the Water Framework Directive.
PMID- 29948701
TI - Immune consequences induced by photodynamic therapy in non-melanoma skin cancers:
a review.
AB - Photodynamic therapy (PDT) is widely used in dermatology to treat precancerous
skin lesions and superficial non-melanoma skin cancers (NMSCs), including
premalignant actinic keratosis, cutaneous squamous cell carcinoma in situ, and
superficial basal cell carcinoma. The long-term cure rates of PDT range from 70
to 90% in NMSC patients, with excellent cosmetic results and good tolerance.
However, the mechanism of action of PDT on tumors is complex. PDT not only kills
tumor cells directly but also rapidly recruits immune cells to release
inflammatory mediators to activate antitumor immunity. PDT-induced tumor death,
also called immunogenic cell death, can trigger both innate and adaptive immune
response, further enhancing the antitumor effect. For instance, inoculation of
tumor cells killed via PDT to animals triggered a stronger antitumor immunity in
vivo than tumor cell lysates produced by other treatments. More importantly, many
immunotherapy regimens based on the immune effect of PDT have been developed and
demonstrated to be a promising therapeutic method for cancer in pre-clinical
trials. Therefore, increasing efforts have been undertaken to investigate the
immune responses associated with PDT. In the present review, we first introduce
the antitumor effect and the associated mechanisms of PDT in cancers. Then, we
summarize studies on the immune responses induced by PDT in NMSCs. We also
discuss the potential mechanisms underlying the process.
PMID- 29948703
TI - Spatial distribution and ecological risk assessment of sediment metals in a
highly industrialized coastal zone southwestern Taiwan.
AB - Spatial variations of Cr, Cu, Hg, Ni, Pb, and Zn in the surface sediments from 34
stations of the Kaohsiung coastal zone southwestern Taiwan were studied to
address the current pollution status, sediment quality, and potential ecological
risk. The study revealed that the concentrations of sediment metals in Kaohsiung
Harbor were alarmingly high compared to the other region of Kaohsiung coast. The
concentrations of Cr, Cu, Hg, Ni, Pb, and Zn in the harbor sediments were as high
as 351, 247, 1.93, 61.8, 60.9, and 940 mg kg-1, respectively. The current
situation of metal pollution was assessed by different pollution indices and
results showed moderate to severe enrichment of Cu, Hg, and Zn in the harbor
sediments. According to the degree of contamination, pollution load index, and
contamination severity index, the sediments from the inner Kaohsiung Harbor show
high degree and high severity of metal contamination, while the rest of Kaohsiung
coastal areas show uncontaminated or low-level pollution. Results of mean ERM
quotient and potential ecological risk index also indicated that the harbor
sediments posed a 49% probability of biological toxicity and very high ecological
risk. The toxic units indicated that the negative biological effects of the six
metals in the harbor sediments were Zn > Cu > Cr > Ni > Hg > Pb. In contrast to
Kaohsiung Harbor as a trap where considerable amount of anthropogenic metal
loadings accumulated in sediments, low metal concentrations were observed in most
Kaohsiung coastal sediments. It probably resulted from the limited fine-grained
sediment deposition. In the wave-dominated Kaohsiung coastal zone, fine-grained
sediments associated with polluted metals tend to be easily resuspended and
transported offshore via waves and wave-induced currents. The results of this
study can provide valuable information for river and coastal zone management.
PMID- 29948705
TI - Biological floating bed and bio-contact oxidation processes for landscape water
treatment: simultaneous removal of Microcystis aeruginosa, TOC, nitrogen and
phosphorus.
AB - The aim of this study was to identify algicidal bacteria J25 against the
Microcystis aeruginosa (90.14%), Chlorella (78.75%), Scenedesmus (not inhibited),
and Oscillatoria (90.12%). Meanwhile, we evaluate the SOD activity and efficiency
of denitrification characteristics with Acinetobacter sp. J25. A novel hybrid
bioreactor combined biological floating bed with bio-contact oxidation (BFBO) was
designed for treating the landscape water, and the average removal efficiencies
of nitrate-N, ammonia-N, nitrite-N, TN, TP, TOC, and algal cells were 91.14, 50,
87.86, 88.83, 33.07, 53.95, and 53.43%, respectively. A 454-pyrosequencing
technology was employed to investigate the microbial communities of the BFBO
reactor samples. The results showed that Acinetobacter sp. J25 was the dominant
contributor for effective removal of N, algal cells, and TOC in the BFBO reactor.
And the relative abundance of Acinetobacter showed increase trend with the delay
of reaction time. Graphical abstract Biological floating bed and bio-contact
oxidation (BFBO) as a novel hybrid bioreactor designed for simultaneous removal
Microcystis aeruginosa, TOC, nitrogen, and phosphorus. And high-throughput
sequencing data demonstrated that Acinetobacter sp. J25 was the dominate species
in the reactor and played key roles in the removal of N, TOC, and M. aeruginosa.
Proposed reaction mechanism of the BFBO.
PMID- 29948704
TI - Antibiotic resistance genes in China: occurrence, risk, and correlation among
different parameters.
AB - Antibiotic resistance has become a widely concerned issue due to the huge risk on
the ecological environment and human health. China has the highest production and
consumption of antibiotics than other countries. Thus, antibiotic resistance
genes (ARGs) have been detected in various environmental settings (e.g., surface
water, wastewater, sediment) in China. The occurrence of ARGs in these matrixes
was summarized and discussed in this review. Sulfonamide resistance genes and
tetracycline resistance genes were the most frequently detected ARGs in China.
According to the abundance of these two classes of ARGs in the natural
environment, sulfonamide resistance genes seem to be more stable than
tetracycline resistance genes. Furthermore, the relationships between ARGs and
antibiotics, antibiotic resistance bacteria (ARB), heavy metals, and
environmental parameters (e.g., pH, organics) were also investigated.
Specifically, relative abundance of total ARGs was found to correlate well with
concentration of total antibiotics in aqueous phase but not in the solid phase
(soil, sediment, sludge, and manure). As for relationship between ARGs and ARB,
metals, and environmental parameters in different media, due to complex and
variable environment, some exhibit positive correlation, some negative, while
others no correlation at all. Three potential risks are discussed in the text:
transmission to human, synergistic effect of different ARGs, and variability of
ARGs. However, due to the complexity of the environment, more work is needed to
establish a quantitative approach of ARG risk assessment, which can provide a
theoretical support for the management of antibiotics and the protection of human
health.
PMID- 29948706
TI - The different effects of natural pyrethrins and beta-cypermethrin on human
hepatocyte QSG7701 cells by ROS-mediated oxidative damage.
AB - With the widespread use of natural pyrethrins and pyrethroids to defend pest
insects, people had the sustained interest in the potential risk to environment
and human health. However, the research about natural pyrethrins and beta
cypermethrin induction of cytotoxicity is still seldom. This study is about the
cytotoxic effects of these on human non-target cells in vitro. The cytotoxic
effect of natural pyrethrins and beta-cypermethrin on QSG7701 cells were
researched by using various bioassays in vitro. The results suggested that with
the natural pyrethrin concentration increased, the viability of QSG7701 cells
were inhibited increasingly, and the IC50 value as calculated was approximately
42.54 and 18.68 MUg/mL after the cells were treated 24 and 48 h. The
proliferative potential of QSG7701 cells treated with 40 MUg/mL natural
pyrethrins 6 and 12 h was decreased by 67.44 and 94.74%, dramatic enhancement
ROS, collapse of mitochondrial membrane potential, DNA exhibit severity of
impairment, and chromatin DNA condensation. However, beta-cypermethrin has lower
toxicity than natural pyrethrins. The IC50 values of beta-cypermethrin were all >
80 MUg/mL, and the colony formation expression was decreased by 15.26 and 19.09%,
which implied that natural pyrethrins are more significantly cytotoxic and
potentially genotoxic to human hepatocyte cells.
PMID- 29948707
TI - Kinetics of atmospheric reactions of 4-chloro-1-butene.
AB - Chloroalkenes are among the important anthropogenic organic compounds emitted in
the atmosphere as a result of their wide use in synthetic processes in industry.
Despite their well-known adverse effects on human health and air quality, the
chemistry of these chloroalkenes remains poorly explored. In this work, reactions
of 4-chloro-1-butene (CBE), a representative example of chloroalkenes, with O3,
OH, NO3, and Cl are investigated in a 100-L Teflon reaction chamber equipped with
gas chromatography-flame ionization detector (GC-FID). The absolute rate method
was used for the reaction with O3 while the relative rate method was used for
reactions with OH, NO3, and Cl. The following rate constants were obtained at
room temperature (298 +/- 2) K and atmospheric pressure: (3.96 +/- 0.43) * 10-18,
(2.63 +/- 0.96) * 10-11, (4.48 +/- 1.23) * 10-15, and (2.35 +/- 0.90) * 10-10 cm3
molecule-1 s-1, for reactions with O3, OH, NO3, and Cl, respectively. Atmospheric
lifetimes of CBE calculated from rate constants of the different reactions
obtained in this work showed that reaction with OH is the main loss process for
CBE, while in coastal areas and in the marine boundary layer, the CBE loss by Cl
reaction becomes important. Estimation of the value of the photochemical ozone
creation potential (POCP) indicated that CBE has a large ozone formation
potential. The present work underlines the need for further studies on the
atmospheric chemistry of chlorinated VOCs.
PMID- 29948708
TI - Polycyclic aromatic hydrocarbons, phthalates, parabens and other environmental
contaminants in dust and suspended particulates of Algiers, Algeria.
AB - Chemicals such as polycyclic aromatic hydrocarbons (PAHs), phthalateesters,
parabens, siloxanes and squalene, all of them classified as endocrine-disrupting
chemicals (EDCs), have been reported to occur in all environmental compartments.
The effects of EDCs on development, reproduction, growth, metabolism and obesity
constitute a real public health issue. A list of EDCs (> 40 compounds) were
characterised in total suspended particulates (outdoor soot: 92 samples)
collected in July-September 2016 in an Algiers urban area; besides, settled
indoor dusts (36 samples) were collected between November and December 2016 in
schools, homes, manufacture and hospital of the same province. The analytical
procedure consisted of ultrasonic bath extraction, column chromatography
separation into fractions of different polarity and gas chromatographic-mass
spectrometric processing. The total loads of phthalates ranging from 6.0 to 347
ng/m2 (median, 26 ng/m2) were determined in indoor dust and 4.6 to 11.6 ng/m3
(median, 7.9 ng/m3) in outdoor soot; meanwhile, PAHs ranged from 12.1 to 108
ng/m2 (median, 36 ng/m2) in indoor dust and ranged from 5.6 to 7.7 ng/m3 (median
5.7 ng/m3) in outdoor soot. Finally, illicit substances such as cocaine,
cannabinol and Delta9-tetrahydrocannabinol were found to range from 0.5 to 11
pg/m3, 4.6 to 9.2 pg/m3 and 11 to 81 pg/m3, respectively, in outdoor soot.
PMID- 29948709
TI - Combustion performance and exhaust emissions fuelled with non-surfactant water-in
diesel emulsion fuel made from different water sources.
AB - Non-surfactant water-in-diesel emulsion fuel (NWD) is an alternative fuel that
has the potential to reduce major exhaust emissions while simultaneously
improving the combustion performance of a diesel engine. NWD comprises of diesel
fuel and water (about 5% in volume) without any additional surfactants. This
emulsion fuel is produced through an in-line mixing system that is installed very
close to the diesel engine. This study focuses mainly on the performance and
emission of diesel engine fuelled with NWD made from different water sources. The
engine used in this study is a direct injection diesel engine with loads varying
from 1 to 4 kW. The result shows that NWD made from tap water helps the engine to
reduce nitrogen oxide (NOx) by 32%. Rainwater reduced it by 29% and seawater by
19%. In addition, all NWDs show significant improvements in engine performance as
compared to diesel fuel, especially in the specific fuel consumption that
indicates an average reduction of 6%. It is observed that all NWDs show
compelling positive effects on engine performance, which is caused by the optimum
water droplet size inside NWD.
PMID- 29948710
TI - Trace element contaminant uptake in phytocap vegetation and implications for
koala habitat, Lismore, Australia.
AB - Phytocapping is increasingly regarded as an economical and environmentally
sustainable post-closure landfill management strategy. During 2013, a phytocap
comprised of koala habitat trees was established on a historic landfill site in
Lismore as part of an Australian trial program (A-ACAP). This case study was
conducted to determine trace element contamination of the Lismore phytocap soil
and foliage, and identify risks to grazing koalas. Foliage of Eucalyptus
tereticornis, a key koala food tree, and Acacia melanoxylon, a reference native
species, were assessed at the phytocap and an uncontaminated reference site.
Concentrations of Ag, As, Hg and Pb were significantly higher in foliage from the
phytocap compared to that from the reference site (p < 0.0001df 7, 52). Mean
trace element concentrations in phytocap E. tereticornis foliage were compliant
with state and international standards for contaminants in food and animal feed
(NSW State Government, 2010; WHO and FAO, 2015) and soil was compliant with
national health-based investigation levels for contaminated sites (NEPC, 2011).
However, contaminant distribution was not homogenous, and As and Pb
concentrations exceeded guidelines in some soil and foliage samples. Based on
available guidelines and weekly dietary intake calculations, risks to koala
health posed by trace element contamination of phytocap foliage are currently
low, though should be managed by continued monitoring as the vegetation matures.
PMID- 29948712
TI - A multi-criteria sustainability assessment framework: development and application
in comparing two food waste management options using a UK region as a case study.
AB - Preventing food wastage is a key element of sustainable resource management. But
as food waste is still generated at high volumes, priority is placed on its
proper management as a resource, maximising sustainability benefits. This study,
by integrating a multi-criteria decision analysis with a sustainability
assessment approach, develops a screening and decision support framework for
comparing the sustainability performance of food waste management options. A
structured process for selecting criteria based on the consideration of
environmental, economic and social aspects related to region-specific food waste
system planning, policy and management has been developed. Two food waste
management options, namely the use of food waste disposal units, which grind food
waste at the household's kitchen sink and discharge it to the sewer, and the
anaerobic co-digestion of separately collected food waste with sewage sludge,
were selected for comparison due to their potential to create synergies between
local authorities, waste and water companies, with local circumstances
determining which of the two options to adopt. A simplified process used for
assessing and comparing the two food waste management options in the Anglian
region in the UK, indicated that there are benefits in using the framework as a
screening tool for identifying which option may be the most sustainable. To
support decision-making, a detailed analysis that incorporates stakeholders'
perspectives is required. An additional use of the framework can be in providing
recommendations for optimising food waste management options in a specific
region, maximising their sustainability performance.
PMID- 29948711
TI - Mg-Fe layered double hydroxide assembled on biochar derived from rice husk ash:
facile synthesis and application in efficient removal of heavy metals.
AB - The pollution of toxic and persistent heavy metals commonly exist in water
environment; such multi-component pollutants pose a serious threat to human
beings and other organisms. Herein, to make full use of the advantages of both
layered double hydroxide (LDH) and rice husk ash (RHA), a novel Mg-Fe-LDH-RHA
functional material was synthesized by assembling LDH on the biochar derived from
RHA and used as an adsorbent for removal of heavy metal ions including Pb2+,
Cu2+, Co2+, Ni2+, Zn2+, and Cd2+. The adsorption kinetics and isotherms of heavy
metal ions in a mono-component system, the adsorption capacities in mixed multi
metal ion system, and the regeneration of the adsorbent were studied in detail.
The results showed that the synthesized Mg-Fe-LDH-RHA might efficiently remove
the above six heavy metals in water under optimized experimental conditions.
Interestingly, the removal performance toward Pb(II) showed high static
distribution coefficients (Kd) of ~ 107 mL/g and maximum capacity of ~ 682 mg/g.
Besides, further characterizations of the adsorbent have been conducted, and the
result suggested the formation of abundant functional groups including hydroxyl,
carbonyl, and carboxyl groups. The removal mechanism of the metal ions might be
related to ion-exchange, surface precipitation, complexation, and hydrogen
binding during the interactions between the LDH-RHA material and pollutants. Such
a facile and environmentally friendly approach, efficient removal performance
suggests that the LDH-RHA material thus has potential for efficient removal of
heavy metals in practical application.
PMID- 29948713
TI - Mineralization and cementing properties of bio-carbonate cement, bio-phosphate
cement, and bio-carbonate/phosphate cement: a review.
AB - Due to high pollution associated with traditional Portland cement and bio
carbonate cement, a new generation of cementitious material needs to be
developed. Bio-barium phosphate, magnesium phosphate, and ferric phosphate are
synthesized by bio-mineralization. Firstly, the substrate is hydrolyzed by
alkaline phosphatase secreted via phosphate-mineralization microbes, obtaining
phosphate ions. Micro- and nano-scale phosphate minerals are prepared by
phosphate ions reacting with different types of metal cation. The setting time of
bio-BaHPO4 has a greater effect on the strength of sand columns when a mixing
precipitation process is innovatively adopted. The strength of the sand columns
increases as bio-BaHPO4 content (10~50%) increases. The optimum content of bio
BaHPO4 is 60%. Porosity and permeability of the sand columns decrease as bio
BaHPO4 content (10~60%) increases. Ammonium and ammonia can effectively be
synthesized to magnesium ammonium phosphate by adding K2HPO4.3H2O to Sporosarcina
pasteurii liquid. Permeability, porosity, and compressive strength of the sand
columns are close to CJ1, CJ1.5, and CJ2 cementation. However, the fixation
ammonia ratio of CJ2 is bigger than CJ1 and CJ1.5 (The mixture solutions of
Sporosarcina pasteurii and K2HPO4.3H2O (1, 1.5, and 2 mol/L) are named as CJ1,
CJ1.5, and CJ2) cementation. The results show that the Sporosarcina pasteurii
liquid containing K2HPO4.3H2O (2 mol/L) and the mixture solution of MgCl2 and
urea (3 mol/L) cemented loose sand particles best. Two types of bio-cement are
environmentally friendly and can partially or completely replace bio-carbonate
cement.
PMID- 29948714
TI - Toxic effects of cyhalofop-butyl on embryos of the Yellow River carp (Cyprinus
carpio var.): alters embryos hatching, development failure, mortality of embryos,
and apoptosis.
AB - As a universal environmental contaminant, the herbicide cyhalofop-butyl is
considered to have infested effects on the embryonic development of aquatic
species. The present study focused on an assessment of the impacts of cyhalofop
butyl on Yellow River carp embryos. It was found that cyhalofop-butyl inhibited
the hatching of the embryos, and the hatching rate decreased with higher
concentrations of the herbicide. The mortality rate was increased on exposure to
cyhalofop-butyl and was significantly higher in the 1.6 and 2 mg/L treatment
groups over 48 h. All of the embryos of the 2 mg/L treatment group died within
the 48 h post-hatching stage. And the transcription of several embryos related to
apoptosis was also influenced by cyhalofop-butyl exposure. Further, cyhalofop
butyl exposure leads to a series of morphological changes (pericardial edema,
tail deformation, and spine deformation) in embryos, which were consistent with
significant modifications in the associated genes. These results provided a
scientific basis for further studies into the effects of cyhalofop-butyl on
aquatic organisms.
PMID- 29948715
TI - Temporal and spatial characteristics of potential energy anomaly in Lake Taihu.
AB - In this study, water temperature and meteorological data in Lake Taihu from June
11 to July 6, 2013, are collected to calibrate and verify the unstructured grid
finite-volume community ocean model (FVCOM) coupled with a heat exchange module.
The spatial and temporal variations of potential energy anomalies (PEA) in the
lake, simulated by the calibrated FVCOM, are analyzed to explore the
stratification and de-stratification processes in water body. The temporal
variation of PEA primarily follows the diurnal cycles of solar radiation, while
the spatial heterogeneity of PEA is jointly determined by solar radiation and
vertical shear of horizontal velocity coupled with the topography of the lake.
The maxima of PEA in the lake are not greater than 4 J/m3 in the summer and even
smaller along shore regions and near the Pingtaishan station. This study is
helpful to improve understanding of the effect of physical processes on the algae
bloom in Lake Taihu.
PMID- 29948716
TI - An empirical analysis of financial development and energy demand: establishing
the role of globalization.
AB - The rapid mode of globalization is experienced in the last few years. The
acceleration in globalization expands economic activities through a share of
knowledge and transfer of technology which influence energy demand. So, the
objective of this empirical work is to explore the impact of financial
development on energy demand incorporating globalization. The empirical finding
is based on autoregressive distributed lag (ARDL) bound testing approach from
1980 to 2016 in case of China. Overall, we infer that financial development
increases energy demand in China. Furthermore, the finding shows that
globalization has a negative and significant impact on energy demand. The
additional determinants, such as economic growth, and urbanization stimulate
energy consumption. Besides, energy consumption granger cause financial
development in the long-run path. Similarly, unidirectional causality is detected
between globalization and energy consumption. The result gives direction to
policymakers to preserve as well as to enhance efficient energy consumption and
sustain economic growth in China with acceleration in globalization.
PMID- 29948717
TI - Arbuscular mycorrhizal fungi enhance antioxidant defense in the leaves and the
retention of heavy metals in the roots of maize.
AB - In this study, we investigated the effects of the arbuscular mycorrhizal fungi
(AMF) Funneliformis mosseae and Diversispora spurcum on the growth, antioxidant
physiology, and uptake of phosphorus (P), sulfur (S), lead (Pb), zinc (Zn),
cadmium (Cd), and arsenic (As) by maize (Zea mays L.) grown in heavy metal
polluted soils though a potted plant experiment. F. mosseae significantly
increased the plant chlorophyll a content, height, and biomass; decreased the
H2O2 and malondialdehyde (MDA) contents; and enhanced the superoxide dismutase
(SOD) and catalase (CAT) activities and the total antioxidant capacity (T-AOC) in
maize leaves; this effect was not observed with D. spurcum. Both F. mosseae and
D. spurcum promoted the retention of heavy metals in roots and increased the
uptake of Pb, Zn, Cd, and As, and both fungi restricted heavy metal transfer,
resulting in decreased Pb, Zn, and Cd contents in shoots. Therefore, the fungi
reduced the translocation factors for heavy metal content (TF) and uptake (TF')
in maize. Additionally, F. mosseae promoted P and S uptake by shoots, and D.
spurcum increased P and S uptake by roots. Moreover, highly significant negative
correlations were found between antioxidant capacity and the H2O2, MDA, and heavy
metal contents, and there was a positive correlation with the biomass of maize
leaves. These results suggested that AMF alleviated plant toxicity and that this
effect was closely related to antioxidant activation in the maize leaves and
increased retention of heavy metals in the roots.
PMID- 29948718
TI - The sources and dispersal of nitrate in multiple waters, constrained by multiple
isotopes, in the Wudalianchi region, northeast China.
AB - The Wudalianchi scenic area in NE China has been named an UNESCO "Global Geopark"
and "Biosphere Reserve." During this investigation, the sources of nitrate and
the hydrologic system through which it is dispersed were assessed using
geochemical data and a multiple isotopic approach. The cold waters from the south
and north springs originated from the deep subsurface. Isotopically, these waters
exhibited relatively negative deltaD and delta18O values and nitrate in the water
was substantially depleted 15N, suggesting that the mineral water was primarily
derived from depth. Lakes within the Wudalianchi region were primarily composed
of water from these deep mineral springs and precipitation. Chemical fertilizers
were the primary source of nitrate to the Wudalianchi lakes. Groundwater was
found in shallow mineral springs and wells plotted above the local meteoric water
line, implying that shallow groundwater was primarily derived from precipitation.
Elevated concentrations of nitrate in shallow mineral springs and well waters
during the summer, autumn, and winter suggest that shallow groundwater within the
Yaoquan volcanic area was also polluted by nitrate from human activities.
Denitrification of shallow groundwater is slow, reducing the potential for "self
remediation". The concentration data are supported by nitrogen (N) isotope data;
wells and springs exhibited N isotopic ratios between - 50/00 and + 50/00
(typical of fertilizers and precipitation) and exhibited higher oxygen (O)
isotope values than water in the Wudalianchi lakes. These relationships suggest
that nitrate in shallow mineral springs, wells, and lakes near the Yaoquan
volcano was derived from the mixing of chemical fertilizers with local summer
rainfall.
PMID- 29948719
TI - Nerve conduction velocity as a non-destructive biomarker in the earthworm
Aporrectodea caliginosa exposed to insecticides.
AB - Earthworms are important and useful soil organisms, but in agricultural soils,
they are potentially exposed to a wide variety of pesticides. Insecticides
represent the highest threat to earthworms and many are neurotoxic. There is a
need for a reliable, relevant, simple biomarker to assess the sub-lethal effects
of neurotoxic insecticides on earthworms under laboratory or field conditions.
The Aporrectodea caliginosa earthworms were exposed to 0 (control), 0.5*, 1*
(normal field application rate), and 5* concentrations of a carbamate
(Pirimor(r)) and an organophosphate (Lorsban(r)) insecticides. The nerve
conduction velocity (NCV) of the medial giant fibers of A. caliginosa earthworm
was recorded on days 0, 1, 2, 3, 4, and 7 to quantify sub-lethal neurotoxic
effects. Acetylcholinesterase (AChE) enzyme activity of A. caliginosa homogenates
was measured at the conclusion of the experiment. Pirimor(r) but not Lorsban(r)
induced a significant decrease in NCV on days 3, 4, and 7 at 1* and 5* doses. A
significant dose-dependent decrease was observed on AChE activity to Pirimor(r)
at the doses used but not Lorsban(r). A clear relationship is observed between
AChE activity and NCV in the case of Pirimor(r). This study showed that NCV is a
sensitive biomarker that correlates well with classical biomarker measurements
such as AChE enzyme activity. This technique could be used to study the impact of
insecticides on earthworms and also their recovery.
PMID- 29948720
TI - Herbicides in river water across the northeastern Italy: occurrence and spatial
patterns of glyphosate, aminomethylphosphonic acid, and glufosinate ammonium.
AB - Glyphosate and glufosinate ammonium are the active ingredients of commonly used
herbicides. Active agricultural lands extend over a large part of the Veneto
region (Eastern Po Valley, Italy) and glyphosate and glufosinate ammonium are
widely used. Consequently, surface waters can be potentially contaminated. This
study investigates the occurrence of glyphosate and glufosinate ammonium as well
as aminomethylphosphonic acid (AMPA, the degradation product of glyphosate) in
river water of Veneto. Eighty-six samples were collected in 2015 at multiple
sampling points across the region. Samples were analyzed for the two target
herbicides, AMPA as well as for other variables, including water temperature, pH,
dissolved oxygen, conductivity, hardness, BOD, COD, inorganic ions, total
nitrogen, total phosphorus, total suspended solids, arsenic, and lead. The
average concentrations (all samples) were 0.17, 0.18, and 0.10 MUg L-1 for
glyphosate, AMPA, and glufosinate ammonium, respectively. The European upper
tolerable level for pesticides (annual average 0.1 MUg L-1) was often exceeded.
Chemometric analysis was therefore applied to (i) investigate the relationships
among water pollutants, (ii) detect the potential sources of water contamination,
(iii) assess the effective water pollution of rivers by identifying river basins
with anomalous pollution levels, and (iv) assess the spatial variability of
detected sources. Factor analysis identified four factors interpreted as
potential sources and processes (use of herbicides, leaching of fertilizers,
urban/industrial discharges, and the biological activity on polluted or stagnant
waters). A discriminant analysis revealed that the pollution from anthropogenic
discharges is homogeneously present in surface water of Veneto, while biological
activity and fertilizers present heterogeneous distributions. This study gives
insights into the concentrations of herbicides in rivers flowing through a wide
region that has heavy use of these chemicals in agriculture. The study also
points out some hot-spots and suggests the future implementation of the current
monitoring protocols and network.
PMID- 29948721
TI - Characterization of outdoor bronze monument patinas: the potentialities of near
infrared spectroscopic analysis.
AB - The corrosion products usually found on outdoor bronzes are generated by the
interaction between the metal alloy and the atmospheric pollutants. To protect
the external surface of bronzes, different organic materials (natural or
synthetic) can be applied, creating over time a patina consisting of a complex
mixture of inorganic and organic degraded components. The correct chemical
characterization of patina constituents is fundamental to define the state of
conservation of a metal artwork and address proper restoration actions. In this
paper, we evaluated the potentialities of near-infrared (NIR) reflectance
microscopy (4000-7500 cm-1) as complementary method to mid-infrared (MIR)
analyses for the characterization of bronze patinas. Although NIR spectroscopy
has been already used in the field of heritage science, its application for the
characterization of bronze patinas is almost unexplored. In this paper, several
corrosion products usually found on the surface of outdoor bronze sculptures were
synthesized, characterized, and submitted to the NIR-MIR total reflection
analysis to build up a reference spectral database. We devoted particular
attention to the NIR features of copper hydroxychlorides, such as atacamite and
paratacamite, which have not been studied in detail up to now. A selection of
organic-based formulations, commonly used by restorers to protect the bronze
surface against the outdoor aggressive environment, were also considered as
references. Successively, NIR-MIR reflectance microscopy was successfully
employed for the analysis of patina micro-samples collected from the bronze
statues of the Neptune Fountain (sixteenth century) located in Bologna. The
obtained results demonstrate the ability of NIR spectroscopy to identify organic
and inorganic patina constituents, even in mixtures. In addition, the study can
be considered as a proof of concept for the possible future application of the
technique for in situ diagnostic campaigns on bronze sculptures.
PMID- 29948722
TI - Simultaneous NO and SO2 removal by aqueous persulfate activated by combined heat
and Fe2+: experimental and kinetic mass transfer model studies.
AB - This study evaluates the chemistry, kinetics, and mass transfer aspects of the
removal of NO and SO2 simultaneously from flue gas induced by the combined heat
and Fe2+ activation of aqueous persulfate. The work involves experimental studies
and the development of a mathematical model utilizing a comprehensive reaction
scheme for detailed process evaluation, and to validate the results of an
experimental study at 30-70 degrees C, which demonstrated that both SO2 and Fe2+
improved NO removal, while the SO2 is almost completely removed. The model was
used to correlate experimental data, predict reaction species and nitrogen-sulfur
(N-S) product concentrations, to obtain new kinetic data, and to estimate mass
transfer coefficient (KLa) for NO and SO2 at different temperatures. The model
percent conversion results appear to fit the data remarkably well for both NO and
SO2 in the temperature range of 30-70 degrees C. The conversions ranged from
43.2 to 76.5% and 98.9 to 98.1% for NO and SO2, respectively, in the 30-70
degrees C range. The model predictions at the higher temperature of 90 degrees C
were 90.0 and 97.4% for NO and SO2, respectively. The model also predicted
decrease in KLa for SO2 of 1.097 * 10-4 to 8.88 * 10-5 s-1 (30-90 degrees C) and
decrease in KLa for NO of 4.79 * 10-2 to 3.67 * 10-2 s-1 (30-50 degrees C) but
increase of 4.36 * 10-2 to 4.90 * 10-2 s-1 at higher temperatures (70-90 degrees
C). This emerging sulfate-radical-based process could be applied to the treatment
of flue gases from combustion sources. Graphical abstract ?.
PMID- 29948723
TI - Effects of arsenic methylation and metabolism on the changes of arsenic-related
skin lesions.
AB - Little was known about the arsenic metabolism and arsenic methylation associated
with the changes of skin lesions after reducing the arsenic in drinking water
(WAs). Therefore, urinary concentrations and proportions of arsenic species were
determined for recovery (RC), improvement (IC), persistent (PE), aggravation
(AC), new incidence (NC), and no sign (HC) groups based on the changes of skin
lesions between before (in 2004) and after (in 2017) WAs reduction. The results
indicate that the urinary concentrations of inorganic arsenic (iAs),
monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total arsenic (TAs)
were much higher for RC and IC groups than for the other groups in 2004, while
these values varied slightly among the groups in 2017. The urinary %iAs of all
the groups was significantly decreased after WAs reduction. In contrast, the
urinary %DMA of RC, IC, AC, and NC groups was increased. From 2004 to 2017, the
PE and HC groups had lower decrease rate of %iAs and %MMA, and increase rate of
%DMA, primary methylation index (PMI), and secondary methylation index (SMI)
after WAs reduction. The adjusted odd ratios (ORs) showed that the RC, IC, AC,
and NC groups were positively related with %iAs and %MMA and were negatively
correlated with %DMA, PMI, and SMI before WAs reduction. It can be concluded that
higher urinary %iAs and %MMA before WAs reduction increased the probability of
skin lesions recovery and improvement, and the risks of skin lesions aggravation
and incidence. Higher increase rate of urinary %DMA was positively associated
with of skin lesions recovery and improvement. Moreover, higher urinary %iAs and
%MMA or lower increase rate of urinary %DMA might increase the risk of skin
lesions aggravation.
PMID- 29948726
TI - Complement Component C3 Promotes Cerebral Ischemia/Reperfusion Injury Mediated by
TLR2/NFkappaB Activation in Diabetic Mice.
AB - Complement component C3 (C3), a key factor in the complement system, is heavily
involved in various inflammation-associated diseases. However, it remains obscure
for its role in the pathogenesis of cerebral ischemia/reperfusion (I/R) injury in
diabetes. A transient middle cerebral artery occlusion (tMCAO) model was used for
cerebral I/R injury in streptozotocin-induced diabetic mice. Cerebral infarct
volume and neurological function were measured at different times of reperfusion.
Complement C3 was measured by ELISA and western blotting. It was observed that
complement C3 expression was increased in cerebral I/R injury of diabetic mice,
whereas complement C3 deficiency abrogated the activation and injury.
Furthermore, activating complement C3 promotes TLR2/NFkappaB activation after I/R
injury in diabetic mice, which is inhibited by of the silencing of TLR2. Taken
together, our data demonstrate that complement C3 promotes cerebral I/R injury
via the TLR2/NFkappaB pathway in diabetic mice, and regulating the complement
C3/TLR2/NFkappaB pathway may be a novel target for therapeutic intervention in
diabetic stroke.
PMID- 29948724
TI - Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through
Improving the Clearance of Peripheral and Central Amyloid-Beta Levels.
AB - Aggregated amyloid beta (Abeta) peptides are believed to play a decisive role in
the pathology of Alzheimer's disease (AD). Previous evidence suggested that
exercise contributes to the improvement of cognitive decline and slows down
pathogenesis of AD; however, the exact mechanisms for this have not been fully
understood. Here, we evaluated the effect of a 4-week moderate treadmill exercise
on spatial memory via central and peripheral Abeta clearance mechanisms following
developed AD-like neuropathology induced by intra-hippocampal Abeta1-42 injection
in male Wistar rats. We found Abeta1-42-treated animals showed spatial learning
and memory impairment which was accompanied by increased levels of amyloid plaque
load and soluble Abeta1-42 (sAbeta1-42), decreased mRNA and protein expression of
neprilysin (NEP), insulin degrading enzyme (IDE) and low-density lipoprotein
receptor-related protein-1 (LRP-1) in the hippocampus. Abeta1-42-treated animals
also exhibited a higher level of sAbeta1-42 and a lower level of soluble LRP-1
(sLRP-1) in plasma, as well as a decreased level of LRP-1 mRNA and protein
content in the liver. However, exercise training improved the spatial learning
and memory deficits, reduced both plaque load and sAbeta1-42 levels, and up
regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Abeta1-42
treated animals. Abeta1-42-treated animals subjected to treadmill exercise also
revealed decreased levels of sAbeta1-42 and increased levels of sLRP-1 in plasma,
as well as increased levels of LRP-1 mRNA and protein in the liver. In
conclusion, our findings suggest that exercise-induced improvement in both of
central and peripheral Abeta clearance are likely involved in ameliorating
spatial learning and memory deficits in an animal model of AD. Future studies
need to determine their relative contribution.
PMID- 29948725
TI - AKR1B1 Upregulation Contributes to Neuroinflammation and Astrocytes Proliferation
by Regulating the Energy Metabolism in Rat Spinal Cord Injury.
AB - Spinal cord injury (SCI) is one of the most common and serious condition, which
leads to permanent neurological dysfunction and poor prognosis in patients.
Hyperglycemia impairs neural functional recovery after SCI resulting in the
overproduction of reactive oxygen species (ROS) and inflammatory cytokines.
However, the effect of glucose metabolism in the spinal cord after injury remains
unclear. AKR1B1, one member of the aldo/keto reductase superfamily, is involved
in the energy metabolism of plasm glucose and ROS production. The role of AKR1B1
in cancer cell proliferation and invasion has been confirmed. Meanwhile, Akt, one
pivotal transcription factor particularly, is involved in the regulation of cell
cycle and ROS-mediated secondary injury in the lesion site. In our study, we
established an acute SCI rat model to identify the expression of AKR1B1 and its
role in neural recovery processes. Western blotting revealed the expression of
AKR1B1 protein was elevated after injury, peaked at 3 days and declined gradually
to normal at 14 days. Similar results was illustrated in immunohistochemistry
staining of white matter. Double immunofluorescence staining showed AKR1B1 was
expressed in glial cells and its expression was significantly increased in
proliferative astrocytes during the pathological processes. Further experiments
showed AKR1B1 was co-located with Akt protein in GFAP positive cells and
immunoprecipitated with Akt in injured spinal cord as well. In summary, the
present study demonstrated AKR1B1 played a vital role in astrocytes proliferation
through Akt pathway, associated with the metabolism of hyperglycemia induced by
SCI.
PMID- 29948727
TI - Localisation of Formyl-Peptide Receptor 2 in the Rat Central Nervous System and
Its Role in Axonal and Dendritic Outgrowth.
AB - Arachidonic acid and docosahexaenoic acid (DHA) released by the action of
phospholipases A2 (PLA2) on membrane phospholipids may be metabolized by
lipoxygenases to the anti-inflammatory mediators lipoxin A4 (LXA4) and resolvin
D1 (RvD1), and these can bind to a common receptor, formyl-peptide receptor 2
(FPR2). The contribution of this receptor to axonal or dendritic outgrowth is
unknown. The present study was carried out to elucidate the distribution of FPR2
in the rat CNS and its role in outgrowth of neuronal processes. FPR2 mRNA
expression was greatest in the brainstem, followed by the spinal cord,
thalamus/hypothalamus, cerebral neocortex, hippocampus, cerebellum and striatum.
The brainstem and spinal cord also contained high levels of FPR2 protein. The
cerebral neocortex was moderately immunolabelled for FPR2, with staining mostly
present as puncta in the neuropil. Dentate granule neurons and their axons (mossy
fibres) in the hippocampus were very densely labelled. The cerebellar cortex was
lightly stained, but the deep cerebellar nuclei, inferior olivary nucleus,
vestibular nuclei, spinal trigeminal nucleus and dorsal horn of the spinal cord
were densely labelled. Electron microscopy of the prefrontal cortex showed FPR2
immunolabel mostly in immature axon terminals or 'pre-terminals', that did not
form synapses with dendrites. Treatment of primary hippocampal neurons with the
FPR2 inhibitors, PBP10 or WRW4, resulted in reduced lengths of axons and
dendrites. The CNS distribution of FPR2 suggests important functions in learning
and memory, balance and nociception. This might be due to an effect of FPR2 in
mediating arachidonic acid/LXA4 or DHA/RvD1-induced axonal or dendritic
outgrowth.
PMID- 29948730
TI - Adams-Oliver Syndrome: Limited Expression.
PMID- 29948728
TI - Neuroprotection of Cytisine Against Cerebral Ischemia-Reperfusion Injury in Mice
by Regulating NR2B-ERK/CREB Signal Pathway.
AB - The aim of the study was to elucidate the therapeutic effects of Cytisine (CYT)
on cerebral ischemia-reperfusion injury in mice. Male ICR mice were pretreated
with reagents (drug), and then subjected to 2 h focal cerebral ischemia and 24 h
reperfusion. Morphologically, the histopathological impairment were estimated by
the TTC, HE and TUNEL staining. The expression of GluN2B-containing NMDA
receptor, phosphorylation of extracellular regulated protein kinases, total ERK,
phosphorylation of cAMP-response element binding protein and total CREB were
determined by immunofluorescence and Western blot assay, respectively. The mRNA
expression of NR2B, ERK and CREB were quantified by the real-time RT-PCR. CYT
significantly diminished the infarct size and neuronal apoptosis. Additionally,
it ameliorated histopathological lesion dramatically. CYT promoted the
phosphorylation of ERK, CREB and their mRNA expression. In contrast, the
expression of NR2B was suppressed in concomitant with the down-regulation of
genes. The overall results thus far suggest that CYT confers the neuroprotection
against cerebral I/R injury by regulating the NR2B-ERK/CREB signal pathway.
PMID- 29948729
TI - What is New in the Management of Childhood Asthma?
AB - Asthma still causes considerable morbidity and mortality globally and minimal
improvement has been seen in key outcomes over the last decade despite increasing
treatment costs. This review summarizes recent advances in the management of
asthma in children and adolescents. It focuses on the need for personalized
treatment plans based on heterogenous asthma pathophysiology, the use of the
terminology 'asthma attack' over exacerbation to instill widespread understanding
of severity, and the need for every attack to trigger a structured review and
focused strategy. The authors discuss difficulties in diagnosing asthma, accuracy
and use of Fractional exhaled nitric oxide both as second line test and as a
method to monitor treatment adherence or guide the choice of pharmacotherapy. The
authors discuss acute and long-term management of asthma. Asthma treatment goals
are to minimize symptom burden, prevent attacks and (where possible) reduce risk
and impact of progressive pathophysiology and adverse outcomes. The authors
discuss pharmacological management; optimal use of short acting beta2 agonists,
long acting muscarinic antagonist (tiotropium), use of which is relatively new in
pediatrics, allergen specific immunotherapy, biological monoclonal antibody
treatment, azalide antibiotic azithromycin, and the use of vitamin D. They also
discuss electronic monitoring and adherence devices, direct observation of
therapy via mobile device, temperature controlled laminar airflow device, and the
importance of considering when symptoms may actually result from dysfunctional
breathing rather than asthma.
PMID- 29948731
TI - Cystic Leucoencephalopathy in NDUFV1 Mutation.
AB - Complex I deficiency is one of the most common mitochondrial respiratory chain
defect. This deficiency of oxidative phosphorylation results from mutation in
nuclear and mitochondrial DNA. Mutations in NDUFV1 (Flavin binding subunit of
Respiratory complex 1) results in neurological manifestations including Leigh
syndrome and leucoencephalopathy. The authors report a one-year-old boy with
history of regression of motor milestones following a trivial fall from the bed.
His magnetic resonance imaging revealed diffuse, cystic leucoencephalopathy
involving corpus callosum and periventricular white matter. Clinical features and
radiological findings may resemble those of vanishing white matter disease. Next
generation sequencing revealed likely compound heterozygous missense pathogenic
variant in exon 8 of NDUFV1 gene [c.1156C > C/T (p.Arg386Cys)] and possibly novel
splice site variation in intron 2 of NDUFV1 gene (c.155 + 1G > G/A). NDUFV1
related leucoencephalopathy must be considered among those presenting with sudden
onset of motor regression with neuroimaging correlate of diffuse cystic
leucodystrophy.
PMID- 29948732
TI - Accidental Mechanical Asphyxia from a Window-Blind Cord.
PMID- 29948733
TI - Rubber Band (Dhaga) Syndrome of the Wrist.
PMID- 29948734
TI - Infiltrating, Quasi-Cancerous Rectal Lesions: Unique Manifestation of Visceral
Basidiobolus ranarum.
AB - OBJECTIVE: To report the finding of transmural rectal involvement, in four
children with lesions which seemed to be neoplastic in appearance and
progression. METHODS: The case records of four children presenting with rectal
involvement by the fungus Basidiobolus ranarum, were retrospectively analyzed for
clinical presentation, hematological and radiological investigations, the
procurement of histopathological material for diagnosis and the findings thereof,
the treatment of these patients and the follow-up. RESULTS: The four children
presented with non-specific symptoms of fever, loss of weight and appetite,
constipation and bleeding per rectum. One presented with excoriation and
ulceration of the perineum and perianal skin. Examination generally unremarkable,
however, showed the rectum extensively involved by a lesion which narrowed the
lumen. Hematological investigations showed leukocytosis with eosinophilia and
raised levels of acute phase reactants like ESR, platelets, and C-reactive
proteins. Ultrasonogram (USG) and CT scan confirmed the lesion to be involving
all layers of the rectum and compromising the rectal lumen. The right colon was
also involved in one patient. One underwent a colonoscopy and biopsy which proved
inconclusive. All four underwent a Tru-cut biopsy which was diagnostic.
Histopathologically the disease was based in Basidiobolus ranarum, a fungus which
is emerging as a cause of visceral abdominal involvement. CONCLUSIONS: Lesions
involving the rectum, and appearing to be neoplastic may be caused by the fungus
Basidiobolus ranarum. The symptomatology and presentation may be non-specific.
High levels of eosinophils in the blood, a raised ESR, and C-reactive protein may
be useful pointers to the diagnosis. USG and CT scans localize the lesions and
also provide a guide for biopsies. The characteristic histopathological findings
are diagnostic and based on these, treatment with Itroconazole / Voriconazole is
beneficial.
PMID- 29948735
TI - Pulmonary Hemorrhage in Children: Etiology, Clinical Profile and Outcome.
AB - OBJECTIVE: To describe etiology, clinical profile, treatment and outcome of
children with pulmonary hemorrhage. METHODS: A chart review of children with
pulmonary hemorrhage attending Pediatric Pulmonology services of a tertiary care
hospital in North-India was done. RESULTS: Data of 44 children (mean age 59.2 +/-
32.1 mo; 28 boys) were included for the study. Possible idiopathic pulmonary
hemosiderosis 16 (36.4%), post infectious complications 11 (25%), immune mediated
disorders 8 (18.2%), cardiac and vascular disorders 7 (15.9%), and airway
pathologies 2 (4.5%) were the etiologies of pulmonary hemorrhage. Treatment
options like medications, bronchial artery embolization and surgical resections
were offered according to the etiology. Children with idiopathic pulmonary
hemosiderosis and those with immune mediated diseases were treated with systemic
steroids and steroid sparing agents; the latter group took longer time to respond
and had more relapses. CONCLUSIONS: Identification of main etiological categories
of pulmonary hemorrhage in children could be useful to plan investigations and
management of wide range of causes in more practical way.
PMID- 29948736
TI - Familial Brachydactyly with Variable Expression in Three Family Members.
PMID- 29948737
TI - Expanding Applications of Prenatal MR Imaging: Detection of Complex Multisystem
Anomalies Made Easy.
PMID- 29948738
TI - Cooking in Iron Pots for Iron Deficiency Anemia: The Traditional Way Forward?
PMID- 29948739
TI - Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow
Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for
Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single
Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.
AB - BACKGROUND: The management of heart failure patients presenting in a moribund
state remains challenging, despite significant advances in the field of
ventricular assist systems. Bridge to decision involves using temporary devices
to stabilize the hemodynamic state of such patients while further assessment is
performed and a decision can be made regarding patient management. The purpose of
this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to
Dicision_01) is to assess the safety and effectiveness of the newly developed
extracorporeal continuous-flow ventricular assist system employing a disposable
centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a
bridge-to-decision therapy for patients with severe heart failure or refractory
cardiogenic shock. METHOD/DESIGN: NCVC-BTD_01 is a single-center, single-arm,
open-label, exploratory, medical device, investigator-initiated clinical study.
It is conducted at the National Cerebral and Cardiovascular Center in Japan. A
total of nine patients will be enrolled in the study. The study was planned using
Simon's minimax two-stage phase design. The primary endpoint is a composite of
survival free of device-related serious adverse events and complications during
device support. For left ventricular assistance, withdrawal of a trial device due
to cardiac function recovery or exchange to other ventricular assist devices
(VADs) for the purpose of bridge to transplantation (BTT) during 30 days after
implantation will be considered study successes. For right ventricular
assistance, withdrawal of tal device due to right ventricular function recovery
within 30 days after implantation will be considered a study success. Secondary
objectives include changes in brain natriuretic peptide levels (7 days after
implantation of a trial device and the day of withdrawal of a trial device),
period of mechanical ventricular support, changes in left ventricular ejection
fraction (7 days after implantation of a trial device and the day of withdrawal
of a trial device), and changes in left ventricular diastolic dimension (7 days
after implantation of a trial device and the day of withdrawal of a trial
device). ETHICS AND DISSEMINATION: We will disseminate the findings through
regional, national, and international conferences and through peer-reviewed
journals. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR;
R000033243) registered on 8 September 2017.
PMID- 29948740
TI - Food as Medicine for Secondary Prevention of Cardiovascular Events Following an
Acute Coronary Syndrome.
AB - Cardiovascular disease is the leading cause of death in men and women in the USA.
Once a patient experiences an acute coronary syndrome (ACS), they are at
increased risk for hospital readmission within 30 days and 6 months after
discharge and more importantly, they have worse survival. Hospital readmissions
lead to poor clinical outcomes for the patient and also significantly increase
healthcare costs due to repeat diagnostic evaluation, imaging, and coronary
interventions. The goal after hospital discharge is to modify cardiovascular (CV)
risk factors including hypertension, hyperlipidemia, and diabetes to prevent
repeat coronary events; however, drug therapy is only one aspect. Several diets
have been shown to decrease weight and reduce these risk factors over short
durations; however, most people typically cannot sustain their diet and regain
the weight. The Intelligent Quisine (IQ) diet is a prepared meal plan that was
designed to meet the American Heart Association and American Diabetes Association
nutritional guidelines and simplify the daily consumption of a nutritionally
complete, calorie conscious meal. The IQ diet has been shown to significantly
reduce blood pressure, cholesterol levels, glucose levels, and weight over a 10
week period. Additional studies have shown that patients are able to remain
compliant on the diet for a year and maintain the reduction of their CV risk
factors. If patients are consistent with a healthy calorie conscious and
nutritionally complete diet modifying CV risk factors long term, then food could
be as powerful in reducing CV events as evidence-based drug therapy. There is a
need to begin conceptualizing food as medicine. To this end, it is time for a
randomized control trial implementing the IQ diet versus current standard dietary
recommendations in a large number of patients and measuring hard CV endpoints.
Many readmissions can be avoided with proper patient education and support
emphasizing lifestyle modifications such as eating healthy and smoking cessation
on a foundation of optimal medical therapy.
PMID- 29948741
TI - Outcome effects of antiretroviral drug combinations in HIV-positive patients with
chemotherapy for lymphoma: a retrospective analysis.
AB - Background The combination of combined active antiretroviral therapy (cART) with
chemotherapy in the treatment of lymphoma in human immunodeficiency virus (HIV)
positive patients has improved the overall survival of these patients. However,
drug-drug interactions between antineoplastic agents and the antiretroviral
agents non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease
inhibitors (PIs) can occur by influencing the activity of the CYP3A4 enzyme. So
far, little is known about the clinical relevance of this interaction: the effect
on the efficacy and toxicity of the chemotherapy. Also, there is no general
consensus which cART is preferable in combination with antineoplastic drugs.
Objective To compare PI-based with NNRTI-based cART on the efficacy and toxicity
of chemotherapy in lymphoma patients. Setting The Onze Lieve Vrouwe Gasthuis,
located in Amsterdam, The Netherlands. Method A retrospective observational
cohort study including all patients with HIV and lymphoma over a 10-year period.
Clinical outcome (response to chemotherapy and survival) and toxicity of
chemotherapy (renal, hepatic and bone marrow toxicity as well as dose reduction,
treatment delay and discontinuation) was compared in patients with PI based and
NNRTI-based cART. Main outcome measure: Response to chemotherapy and survival.
Results Patients using PI-based cART (n = 22) had a significantly lower 1 year
survival compared to NNRTI-based cART (n = 21). No significant differences were
observed in reaching complete remission after chemotherapy. No overall
significant differences in toxicity and discontinuation of the chemotherapy were
observed. However, there was a trend towards more severe bone-marrow toxicity in
patients with PI-based cART. In addition, patients with PI-based cART received
earlier dose-reduction and treatment delay, indicating increased toxicity in PI
treated patients. Conclusion This retrospective study shows that PI-based cART is
inferior in combination with chemotherapy to NNRTI-based cART: a lower 1 year
survival is observed and dose-reduction and treatment delay occur earlier,
possibly based on an earlier onset of toxicity.
PMID- 29948742
TI - Appropriateness of vancomycin therapeutic drug monitoring and its outcomes among
non-dialysis patients in a tertiary hospital in Singapore.
AB - Background Vancomycin therapeutic drug monitoring (TDM) is commonly performed to
ensure safe and effective use of the antibiotic. Aim of Study To evaluate
appropriateness of vancomycin TDM and its outcomes in Singapore General Hospital.
Method A retrospective, cross-sectional study was conducted between 1 January
2014 and 28 February 2014 involving patients who received >= 1 dose of
intravenous vancomycin with TDM. Patient demographics and relevant vancomycin TDM
data were collected from medical records. Results Of 746 vancomycin troughs
measured among 234 patients, 459 troughs (61.5%) were taken inappropriately, with
a median time of 2.6 h (interquartile range 1.1-4.3) before the next scheduled
dose. Inappropriate interpretation of vancomycin troughs resulted in 41
unnecessary dose suspensions, 24 dose changes, and 102 unchanged vancomycin
doses. The cost incurred due to inappropriate interpretation and measurement
after discontinuation of treatment was US$7286. No differences in rates of
vancomycin related nephrotoxicity, ototoxicity, recurrent infection, development
of infection secondary to vancomycin resistant microorganism and mortality were
observed (p > 0.05). Conclusion This study highlighted a high incidence of
inappropriate vancomycin TDM which has led to increased healthcare cost.
PMID- 29948743
TI - An historical overview over Pharmacovigilance.
AB - Pharmacovigilance started about 170 years ago, although it was not yet named as
such at that time. It is structured activity in the professional health field,
with important social and commercial implications aimed at monitoring the
risk/benefit ratio of drugs, improving patient's safety and the quality of life.
In this commentary we report the milestones of pharmacovigilance up to the
present day, in order to understand all the steps that have characterized the
historical evolution; from the first reports, which were essentially letters or
warnings sent by clinicians to publishers of important and famous scientific
journals, up to today's modern and ultra-structured electronic registries. The
historical phases also help us to understand why pharmacovigilance helped us to
achieve such important results for man's health and for pharmacology itself, and
to identify the challenges that await Pharmacovigilance in future years.
PMID- 29948744
TI - Learning the effects of psychotropic drugs during pregnancy using real-world
safety data: a paradigm shift toward modern pharmacovigilance.
AB - The growing evidence on psychotropic drug safety in pregnancy has been possible
thanks to the increasing availability of real-world data, i.e. data not collected
in conventional randomised controlled trials. Use of these data is a key to
establish psychotropic drug effects on foetal, child, and maternal health.
Despite the inherent limitations and pitfalls of observational data, these can
still be informative after a critical appraisal of the collective body of
evidence has been done. By valuing real-world safety data, and making these a
larger part of the regulatory decision-making process, we move toward a modern
pregnancy pharmacovigilance. The recent uptake of real-world safety data by
health authorities has set the basis for an important paradigm shift, which is
integrating such data into drug labelling. The recent safety assessment of sodium
valproate in pregnant and childbearing women is probably one of the first
examples of modern pregnancy pharmacovigilance.
PMID- 29948745
TI - Altered gene expression in lymphoblastoid cell lines after subculture.
AB - Lymphoblastoid cell lines (LCLs) are nearly immortalized B lymphocytes that are
used as long-lasting supply of human cells for studies on gene expression
analyses. However, studies on the stability of the cellular features of LCLs are
scarce. To address this issue, we measured gene expression in LCLs with different
passage numbers and observed that gene expression substantially changed within 10
passages. In particular, the expression of glyceraldehyde-3-phosphate
dehydrogenase (GAPDH), a well-known housekeeping gene, varied considerably during
subculture; thus, the use GAPDH as an internal control may be unsuitable. In
conclusion, this study highlights the need for exercising caution during
determination of gene expression in LCLs.
PMID- 29948746
TI - Nacre formation by epithelial cell cultures from mantle of the black-lip pearl
oyster, Pinctada margaritifera.
AB - Mantle tissue from the black-lip pearl oyster, Pinctada margaritifera, was
cultured in vitro using sterilized seawater supplemented with 0.1% yeast extract
as the culture medium. Granular and agranular epithelial cells, hyalinocytes, and
fibroblast-like cells were observed in the initial stages of culture. Epithelial
cells later formed pseudopodial cell networks containing clusters of granulated
cells, which upon maturation released their colored granules. These granules
induced formation of nacre crystal deposits on the bottom of the culture plate.
Cultures comprised of only granulated epithelial cells were established through
periodic sub-culturing of mantle cells and maintained for over 18 mo in a viable
condition. Reverse transcriptase PCR of cultured cells demonstrated gene
expression of the shell matrix protein, nacrein. To further evaluate the
functional ability of cultured granulated epithelial cells, nuclear shell beads
were incubated in culture medium containing these cells to induce nacre formation
on the beads. Observation of the bead surface under a stereomicroscope at
periodic intervals showed the gradual formation of blackish yellow colored nacre
deposits. Examination of the bead surface by scanning electron microscopy and
energy dispersive X-ray analysis at periodic intervals revealed a distinct brick
and mortar formation characteristic of nacre, comprised of aragonite platelets
and matrix proteins. Calcium, carbon, and oxygen were the major elements in all
stages examined. Our study shows that mantle epithelial cells in culture retain
the ability to secrete nacre and can therefore form the basis for future studies
on the biomineralization process and its application in development of
sustainable pearl culture.
PMID- 29948748
TI - Honoring eight senior distinguished plant biologists from India.
AB - We summarize here research contributions of eight stalwarts in photosynthesis
research from India. These distinguished scientists (Shree Kumar Apte, Basanti
Biswal, Udaya C. Biswal, Agepati S. Raghavendra, Attipalli Ramachandra Reddy,
Prafullachandra Vishnu (Raj) Sane, Baishnab Charan Tripathy, and Dinesh C.
Uprety) were honored on November 2, 2017, at the School of Life Sciences,
University of Hyderabad. We include here two group photographs of this special
event, which was organized by the Department of Plant Sciences, during the 8th
International Conference on Photosynthesis and Hydrogen Energy Research for
Sustainability-2017 ( https://prs.science/wp
content/uploads/2017/10/Photosynthesis-Research-for-Sustainability-2017.pdf ,
also available at: http://www.life.illinois.edu/govindjee/world-historical.html
). The main conference had honored three international scientists: William Cramer
(Purdue University. West Lafayette, Indiana, USA), Govindjee (University of
Illinois at Urbana-Champaign, Illinois, USA, one of the authors here); and
Agepati S. Raghavendra (University of Hyderabad, India, one of those honored here
as well); see papers in this Special Issue, edited by Suleyman Allakhverdiev, one
of the authors here.
PMID- 29948747
TI - Development of fluorescence quenching in Chlamydomonas reinhardtii upon prolonged
illumination at 77 K.
AB - Low-temperature fluorescence measurements are frequently used in photosynthesis
research to assess photosynthetic processes. Upon illumination of photosystem II
(PSII) frozen to 77 K, fluorescence quenching is observed. In this work, we
studied the light-induced quenching in intact cells of Chlamydomonas reinhardtii
at 77 K using time-resolved fluorescence spectroscopy with a streak camera setup.
In agreement with previous studies, global analysis of the data shows that
prolonged illumination of the sample affects the nanosecond decay component of
the PSII emission. Using target analysis, we resolved the quenching on the PSII
684 compartment which describes bulk chlorophyll molecules of the PSII core
antenna. Further, we quantified the quenching rate constant and observed that as
the illumination proceeds the accumulation of the quencher leads to a speed up of
the fluorescence decay of the PSII-684 compartment as the decay rate constant
increases from about 3 to 4 ns- 1. The quenching on PSII-684 leads to indirect
quenching of the compartments PSII-690 and PSII-695 which represent the red
chlorophyll of the PSII core. These results explain past and current observations
of light-induced quenching in 77 K steady-state and time-resolved fluorescence
spectra.
PMID- 29948749
TI - Hybrid complexes of photosynthetic reaction centers and quantum dots in various
matrices: resistance to UV irradiation and heating.
AB - The effects of ultraviolet (UV) irradiation (up to 0.6 J/cm2) and heating (65
degrees C, 20 min) on the absorption spectra and electron transfer in dehydrated
film samples of photosynthetic reaction centers (RCs) from purple bacterium
Rhodobacter (Rb.) sphaeroides, as well as in hybrid structures consisting of RCs
and quantum dots (QDs), have been studied. The samples were placed in organic
matrices containing the stabilizers of protein structure-polyvinyl alcohol (PVA)
and trehalose. UV irradiation led to partially irreversible oxidation of some
RCs, as well as to transformation of some fraction of the bacteriochlorophyll
(BChl) molecules into bacteriopheophytin (BPheo) molecules. In addition, UV
irradiation causes degradation of some BChl molecules that is accompanied by
formation of 3-acetyl-chlorophyll a molecules. Finally, UV irradiation destroys
the RCs carotenoid molecules. The incorporation of RCs into organic matrices
reduced pheophytinization. Trehalose was especially efficient in reducing the
damage to the carotenoid and BChl molecules caused by UV irradiation. Hybrid
films containing RC + QD were more stable to pheophytinization upon UV
irradiation. However, the presence of QDs in films did not affect the processes
of carotenoid destruction. The efficiency of the electronic excitation energy
transfer from QD to P865 also did not change under UV irradiation. Heating led to
dramatic destruction of the RCs structure and bacteriochlorins acquired the
properties of unbound molecules. Trehalose provided strong protection against
destruction of the RCs and hybrid (RC + QD) complexes.
PMID- 29948750
TI - Remembering Otto Kandler (1920-2017) and his contributions.
AB - After a brief prologue on Otto Kandler's life, we describe briefly his pioneering
work on photosynthesis (photophosphorylation and the carbon cycle) and his key
participation in the discovery of the concept of three forms of life (Archaea,
Prokarya, and Eukarya). With Otto Kandler's passing, both the international
photosynthesis and microbiology communities have lost an internationally unique,
eminent, and respected researcher and teacher who exhibited a rare vibrancy and
style.
PMID- 29948751
TI - Oxytocin Induces Mammary Epithelium Disruption and Could Stimulate Epithelial
Cell Exfoliation.
AB - Mammary epithelial cells (MEC) are exfoliated from the epithelium into milk,
influencing the number of MEC present in the udder. This process is associated
with epithelium integrity. The release of oxytocin (OT) induced by milking causes
myoepithelial cell contraction, which, in turn, may stimulate MEC exfoliation
through mechanical forces. To investigate the role of OT in MEC exfoliation, we
inhibited or induced myoepithelial cell contraction by injecting the OT receptor
antagonist atosiban (Ato) or a supraphysiological dose of OT, respectively. Eight
cows were assigned to 2 treatments during 2 milkings according to a crossover
experimental design: Control+OT (cows were first milked to collect standard milk
and then received 5 IU of OT to collect residual milk through a second milking)
and Ato + OT (cows were injected with Ato (50 MUg/kg of body weight) and milked
to collect cisternal milk, then received 5 IU of OT to collect alveolar milk
through a second milking). Milk MEC were purified to determine their
concentration and number in milk. Mammary epithelium integrity was assessed by
measuring the kinetics of plasma lactose concentration. Inhibiting myoepithelial
cell contraction by Ato injection decreased the number of exfoliated MEC in milk.
In contrast, OT injection increased the concentration of MEC in the residual milk
and the number of MEC in the alveolar milk. Ato injection reduced plasma lactose
concentration, whereas, in both treatments, OT injections increased it. Our
results suggested that myoepithelial cell contraction caused by OT could
stimulate MEC exfoliation into milk and was associated with epithelium
disruption.
PMID- 29948752
TI - Cathelicidin Related Antimicrobial Peptide (CRAMP) Enhances Bone Marrow Cell
Retention and Attenuates Cardiac Dysfunction in a Mouse Model of Myocardial
Infarction.
AB - BACKGROUND: Acute myocardial infarction (MI) and the ensuing ischemic heart
disease are approaching epidemic state. Unfortunately, no definitive therapies
are available and human regenerative therapies have conflicting results. Limited
stem cell retention following intracoronary administration has reduced the
clinical efficacy of this novel therapy. Cathelicidin related antimicrobial
peptides (CRAMPs) enhance chemotactic responsiveness of BMSPCs to low SDF-1
gradients, suggesting a potential role in BMSPCs engraftment. Here, we assessed
the therapeutic efficacy of CRAMPs in the context of BMSPCs recruitment and
retention via intracardiac delivery of CRAMP-treated BMSPCs or CRAMP-releasing
hydrogels (HG) post-AMI. METHODS: For cell transplantation experiments, mice were
randomized into 3 groups: MI followed by injection of PBS, BMMNCs alone, and
BMMNCs pre-incubated with CRAMP. During the in vivo HG studies, BM GFP chimera
mice were randomized into 4 groups: MI followed by injection of HG alone, HG +
SDF-1, HG + CRAMP, HG + SDF-1 + CRAMP. Changes in cardiac function at 5 weeks
after MI were assessed using echocardiography. Angiogenesis was assessed using
isolectin staining for capillary density. RESULTS: Mice treated with BMMNCs pre
incubated with CRAMP had smaller scars, enhanced cardiac recovery and less
adverse remodeling. Histologically, this group had higher capillary density.
Similarly, sustained CRAMP release from hydrogels enhanced the therapeutic effect
of SDF-1, leading to enhanced functional recovery, smaller scar size and higher
capillary density. CONCLUSION: Cathelicidins enhance BMMNC retention and
recruitment after intramyocardial administration post-AMI resulting in
improvements in heart physiology and recovery. Therapies employing these
strategies may represent an attractive method for improving outcomes of
regenerative therapies in human studies.
PMID- 29948754
TI - Direct oral anticoagulants for the treatment of venous thromboembolism in
patients with active malignancy: a systematic review and meta-analysis.
AB - Low molecular weight heparins (LMWHs) are considered the standard of care for the
treatment of venous thromboembolism (VTE) associated with cancer. We conducted a
meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants
(DOACs) in patients with cancer. We systematically searched Medline for potential
randomized-control clinical trials (RCTs) and post-hoc analyses. For each study,
data on recurrent VTE, major or clinically relevant non-major bleeding (CRNMB),
and major bleeding (MB) were extracted. Initially, a total of 1395 citations were
identified. Eight studies met our eligibility criteria. The utilization of DOACs
in patients with cancer showed a statistically significant reduction in the risk
of VTE recurrence compared to LMWH or warfarin (RR = 0.64; 95% CI 0.46-0.88).
Similar rates of major or CRNMB were observed between DOACs and LMWH or warfarin
(RR = 1.00; 95% CI 0.75-1.33). There was no significant difference in the rate of
MB between DOACs and LMWH or warfarin (RR = 1.31; 95% CI 0.71-2.44). Our results
suggest that DOACs might reduce the incidence of VTE recurrence in patients with
cancer without putting them at high risk for MB/CRNMB or MB. Our findings were
mainly driven by the results of the Hokusai VTE Cancer trial. Given the level of
investigated evidence, our findings should be interpreted with caution since the
majority of the data were originated from sub-group analyses of large (RCTs).
Future studies that are adequately powered are warranted to assess efficacy and
safety data of DOACs for the treatment of VTE in patients with different types of
cancer.
PMID- 29948753
TI - Incognito: Are Microchimeric Fetal Stem Cells that Cross Placental Barrier Real
Emissaries of Peace?
AB - Chimerism occurs naturaly throughout gestation and can also occur as a
consequence of transfusion and transplantation therapy. It consists of the
acquisition and long-term persistence of a genetically distinct population of
allogenic cells inside another organism. Previous reports have suggested that
feto-maternal microchimerism could exert a beneficial effect on the treatment of
hematological and solid tumors in patients treated by PBSCT. In this review we
report the mechanism of transplacental fetal stem cell trafficking during
pregnancy and the effect of their long-term persistence on autoimmunity, GVHD,
PBSCT, cancer and stem cell treatment.
PMID- 29948755
TI - microRNAs regulate nitric oxide release from endothelial cells by targeting NOS3.
AB - Endothelial nitric oxide synthase (eNOS) encoded by nitric oxide synthase 3
(NOS3), can generate nitric oxide (NO) which serves as an important deterrent to
the pathogenesis of thrombosis by modulating the activation, adhesion and
aggregate formation of platelets. Three serum miRNAs (miR-195, miR-532 and miR
582) have been suggested as biomarkers for the diagnosis of deep vein thrombosis
(DVT), however their potential roles in DVT is not clear. The effect of miRNAs
inhibiting the expression of NOS3 was evaluated in vitro. miR-195, miR-532 and
miR-582 mimic, inhibitor, and control miRNAs were transfected into endothelial
cells. The roles of miR-195, miR-532 and miR-582 regulating the expression of
eNOS were evaluated by real-time quantitative PCR, Western Blotting and
luciferase reporter assays. NO release was measured by Griess method. We
confirmed NOS3 as a direct target of miR-195 and miR-582, which binds to the 3'
UTR of NOS3 mRNA in endothelial cells. A significantly inverse correlation
between these two miRNAs and eNOS expression was detected. NO release from
endothelial cells was decreased when the expression level of miR-195 and miR-582
was up-regulated. These findings indicated that miR-195 and miR-582 regulated NO
release by targeting 3'-UTR of NOS3 post-transcriptionally in endothelial cells.
Therefore, miR-195 and miR-582 might play an important role in maintaining
endothelial NO bioavailability and could be a novel target for treatment of
thrombotic diseases.
PMID- 29948757
TI - Non-vitamin K antagonist oral anticoagulants in cardioversion of atrial
fibrillation: a network meta-analysis.
PMID- 29948756
TI - Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of
patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation
Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and
ARISTOTLE trials.
AB - Randomized controlled trials (RCTs) examining warfarin use for stroke prevention
in atrial fibrillation (AF) may not accurately reflect real-world populations. We
aimed to determine the representativeness of the RCT populations to real-world
patients and to describe differences in the characteristics of trial populations
from trial eligible patients in a real-world setting. We hypothesized that a
significant fraction of real-world patients would not qualify for the RE-LY,
ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the
studies may have more strokes and bleeding events. We compared the inclusion and
exclusion criteria, patient characteristics, and clinical outcomes from RE-LY,
ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality
Improvement Initiative (MAQI2), a regional network of six community- and academic
based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI2
registry taking warfarin, approximately 40-60% would meet the selection criteria
used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%).
The most common reasons for exclusion from one or more trial were anemia (15.1%),
other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial
eligible MAQI2 patients were older, more frequently female, with a higher rate of
paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and
previous myocardial infarction than the trial populations. MAQI2 patients
eligible for each trial had a lower rate of stroke and similar rate of major
bleeding than was observed in the trials. A sizable proportion of real-world AF
patients managed in anticoagulation clinics would not have been eligible for the
RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and
bleeding risk among real-world AF patients on warfarin may not be congruent with
published clinical trial data.
PMID- 29948758
TI - Food Composition Tables in Southeast Asia: The Contribution of the SMILING
Project.
AB - Objectives Food composition data are key for many nutrition related activities in
research, planning and policy. Combatting micronutrient malnutrition among women
and young children using sustainable food based approaches, as aimed at in the
SMILING project, requires high quality food composition data. Methods In order to
develop capacity and to align procedures for establishing, updating and assessing
the quality of key nutrient data in the food composition tables in Southeast
Asia, a detailed roadmap was developed to identify and propose steps for this.
This included a training workshop to build capacity in the field of food
composition data, and alignment of procedures for selecting foods and nutrients
to be included for quality assessment, and update of country specific food
composition tables. The SEA partners in the SMILING project finalised a country
specific food composition table (FCT) with updated compositional data on selected
foods and nutrients considered key for designing nutrient dense and optimal diets
for the target groups. Results Between 140 and 175 foods were selected for
inclusion in the country specific FCTs. Key-nutrients were: energy, protein,
total fat, carbohydrates, iron, zinc, (pro-)-vitamin A, folate, calcium, vitamin
D, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12 and vitamin C. A
detailed quality assessment on 13 key-foods per nutrient was performed using
international guidelines. Nutrient data for specific local food items were often
unavailable and data on folate, vitamin B12 and vitamin B6 contents were mostly
missing. For many foods, documentation was not available, thereby complicating an
in-depth quality assessment. Despite these limitations, the SMILING project
offered a unique opportunity to increase awareness of the importance of high
quality well documented food composition data. Conclusion for Practise The self
reported data quality demonstrated that there is considerable room for
improvement of the nutrient data quality in some countries. In addition,
investment in sustainable capacity development and an urgent need to produce and
document high quality data on the micronutrient composition of especially local
foods is required.
PMID- 29948759
TI - Postpartum Hospital Utilization among Massachusetts Women with Intellectual and
Developmental Disabilities: A Retrospective Cohort Study.
AB - Objectives This study examined the risk of postpartum hospital admissions and
emergency department (ED) visits among US women with intellectual and
developmental disabilities (IDD). Methods We used the 2002-2012 Pregnancy to
Early Life Longitudinal Data System and identified deliveries to women with and
without IDD. Women with IDD (n = 1104) or case subjects were identified from the
International Classification of Diseases and Related Health Problems 9th Revision
(ICD-9 CM) codes. The study primary outcome measures were any postpartum hospital
admission and any ED visit during three critical postpartum periods (1-42, 43-90,
and 1-365 days). We conducted unadjusted and adjusted survival analysis using Cox
proportional hazard models to compare the occurrence of first hospital admission
or ED visits between women with and without IDD. Results We found that women with
IDD had markedly higher rates of postpartum hospital admissions and ED visits
during the critical postpartum periods (within 1-42, 43-90, and 91-365 days)
after a childbirth. Conclusion for Practice Given the heightened risk of
pregnancy complications and adverse birth outcomes and the findings of this
study, there is an urgent need for clinical guidelines related to the frequency
and timing of postpartum care among new mothers with IDD. Further, this study
provides evidence of the need for evidence-based interventions for new mothers
with IDD to provide preventive care and routine assessments that would identify
and manage complications for both the mother and the infant outside of the
traditional postpartum health care framework.
PMID- 29948760
TI - Affluent-Born White Mother's Descending Neighborhood Income and Infant Mortality:
A Population-Based Study.
AB - Objectives To determine whether affluent-born White mother's descending
neighborhood income is associated with infant mortality rates (< 365 day, IMR).
Methods Stratified and multilevel logistic regression analyses were completed on
the Illinois transgenerational dataset of singleton births (1989-1991) to non
Latina White mothers (1956-1976) with an early-life residence in affluent
neighborhoods (defined as the fourth quartile of income distribution). The
breadth of descending neighborhood income was defined by mother's neighborhood
income at the time of delivery. Results Infants of White mothers (n = 4890) who
did not suffer descending neighborhood income by the time of delivery had a first
year mortality rate of 5.1/1,000. Infants of White mothers who experienced minor
(n = 5112), modest (n = 2158), or extreme (n = 339) descending neighborhood
income had IMR of 6.5/1,000, 14.4/1,000, and 11.8/1,000, respectively; RR [95%
CI] = 1.3 [0.8, 2.1], 2.8 [1.7, 4.8], and 2.3 [0.8, 6.6], respectively. The
incidence of young maternal age, inadequate prenatal care utilization, and
cigarette smoking rose as descending neighborhood income increased, p < 0.01. In
multilevel logistic regression models, the adjusted (controlling for selected
individual-level co-variates) OR [95% CI] of infant mortality for White women
with an early-life residence in affluent neighborhoods who subsequently
experienced minor or modest to extreme (versus absent) descending neighborhood
income equaled 1.0 [0.6, 1.8] and 2.1 [1.1, 3.8] respectively. Conclusions White
mother's modest to extreme descending neighborhood income from early-life
residence in affluent neighborhoods is associated with a twofold greater risk of
infant mortality independent of selected biologic, medical, and behavioral
characteristics.
PMID- 29948761
TI - Triadic Interactions in MIECHV: Relations to Home Visit Quality.
AB - Objectives This study was conducted to look inside home visits to examine active
intervention ingredients used and their relations with ratings of home visit
quality. In particular, triadic interactions that engage the home visitor,
parent, and child together and provide a context for home visitors to facilitate
parent-child interactions by observing, modeling and coaching behaviors that
promote optimal child development were examined. Methods Observations were
conducted to describe intervention activities (with the HVOF-R) and rate quality
of home visit practices and engagement (with the HOVRS A+). Results Analyses
revealed the majority of home visit time (71%) was spent in home visitor-parent
interactions with only a small proportion of home visit time (17%) spent in
triadic interactions and an even smaller proportion of time (2%) during which
home visitors actively coached parent-child interactions. Amount of time spent in
triadic interactions was related positively to quality ratings of home visit
practices and engagement. Moreover, time spent coaching parent-child interactions
uniquely predicted home visit quality after accounting for visit length and home
visitor time spent observing and modeling. Conclusions for Practice Increasing
the percentage of home visitors engage the parent and child in triadic
interaction should be a focus for home visiting programs. Home visitors will
likely need professional development and supervisory support to enhance their
skills in coaching parent-child interactions during triadic interactions.
PMID- 29948762
TI - Impact of the 340B Pharmacy Program on Services and Supports for Persons Served
by Hemophilia Treatment Centers in the United States.
AB - Purpose Hemophilia Treatment Centers (HTCs) provide integrated and comprehensive
services to individuals affected with rare bleeding disorders, such as hemophilia
and Von Willebrand disease. Through the 340 Drug Pricing Program, HTCs may use
pharmacy income to support clinical staff and patient services. The objective of
this study was to describe the impact of the 340B program funding on services and
support provided by HTCs to persons affected by rare bleeding disorders.
Description Federally designated comprehensive HTCs with established 340B
programs were invited to participate in a mailed survey in 2014. Participants
were requested to report on 340B program-funded staff and services in the
calendar year 2013. Assessment The 31 of 37 HTCs responding served over 10,000
individuals, or one-third of the national HTC patient population. The majority of
responding HTCs reported that 340B program income supported over 90% of staff
such as nurses, social workers, and physical therapists. Conclusion The results
from this survey of 31 centers with established programs demonstrates the HTCs'
reliance on 340B program support for vital comprehensive services, that are
otherwise non-reimbursable, and highlights the importance of the 340B program in
sustaining the high quality of care and in increasing access for a geographically
dispersed, medically vulnerable population.
PMID- 29948763
TI - What's Happening During Home Visits? Exploring the Relationship of Home Visiting
Content and Dosage to Parenting Outcomes.
AB - Introduction Research has documented modest positive impacts of early childhood
home visiting programs. However, understanding more about what home visitors do
during visits and how much time they spend on specific topics may provide insight
into the variability in effectiveness of services. Methods Outcome data were
collected via parent survey at program enrollment and 12 months from 123 women in
three MIECHV-funded home visiting models. Home visitors completed weekly home
visit content and activity logs. Results Families received an average of 28
visits during the study (3.1 visits per month). Of ten content areas, the three
most often discussed were early childhood development, physical care of children,
and the parent-child-relationship. Multivariate regression models were used to
explore the association of home visit dosage, home visit content and cumulative
risk factors on parenting outcomes. Women whose visits were focused more on
parenting topics reported lower parenting-related stress at follow-up compared to
those whose visits had less parenting content. Additionally, higher-risk women
who received greater numbers of home visits showed larger reductions in their
attitudes about harsh punishment over time, compared to high-risk women with
fewer home visits. Discussion Receiving home visits that emphasize parenting
content may contribute to reduced parenting-related stress. For high-risk women
in particular, receiving more visits overall may be important to achieving
positive outcomes. Implications for practice include working to engage and retain
high-risk families. Future home visiting research calls for improved methods for
collecting data on content/activity during visits, the necessity for long-term
follow-up, and testing for the effectiveness of varied and flexible visit
schedules/content focus for women and families with trauma exposure.
PMID- 29948764
TI - Maternal Depressive Symptoms Mediate the Association between Socio-economic
Status and Adolescent Weight Outcomes: A Longitudinal Analysis.
AB - Introduction The prevalence of pediatric obesity is an issue in the United
States, in which approximately one-third of children and adolescents are
overweight or obese. Youth living in low socioeconomic (SES) households are at an
increased risk for developing obesity; yet, research is needed to understand the
mechanisms that might better explain the relationship between SES and obesity
risk. Maternal depression presents a potential mechanism by which SES might
predict a later risk for obesity in pediatric populations. Methods The present
study used a national dataset from the National Institute of Child Health and
Human Development-Study of Early Child Care and Youth Development (NICHD-SECCYD)
to examine whether maternal depressive symptoms (at an age of 9 years) mediated
the association between early SES (the income-to-needs ratio measured at an age
of 1 month) and adolescent weight outcomes [Body Mass Index z-scores (zBMI) for
age and sex, at an age of 15 years]. Results The results suggested that greater
maternal depressive symptoms helped to explain a significant amount of the
variance of lower SES predicting poorer weight outcomes in adolescents.
Discussion These findings illustrate the role of maternal depressive symptoms in
explaining how SES predicts adolescent weight outcomes. Implications are
discussed, and future research is needed to identify women from lower SES
households who are experiencing depressive symptoms to provide support and
initiate points of early intervention to address relevant health outcomes in
youths.
PMID- 29948765
TI - 18F-FET-PET as a biomarker for therapy response in non-contrast enhancing glioma
following chemotherapy.
AB - BACKGROUND: Monitoring treatment response after chemotherapy of gadolinium-(Gd)
negative gliomas is challenging as conventional MRI often indicates no
radiological changes. We hypothesize that 18F-FET-PET can be used as a biomarker
for response assessment in Gd-negative gliomas undergoing chemotherapy. METHODS:
Sixty-one patients harboring Gd-negative WHO grade II or III glioma receiving
alkylating agents (temozolomide or CCNU/procarbacine) were included. All patients
underwent MRI and 18F-FET-PET before chemotherapy and 6 months later. We
calculated T2-volume, 18F-FET-PET based biological tumour volume (BTV) and
maximal tumour-to-brain ratio (TBRmax). Moreover, dynamic PET acquisition was
performed using time-activity-curves (TACs) analysis. For MRI-based response
assessment, RANO criteria for low-grade glioma were used. For 18F-FET-PET,
following classification scheme was tested: responsive disease (RD) when a
decrease in either BTV >= 25% and/or TBRmax >= 10% occurred, an increase in BTV
>= 25% and/or TBRmax increase > 10% characterized progressive disease (PD), minor
changes +/- 25% for BTV and +/- 10% for TBRmax were regarded as stable disease
(SD). Post-chemotherapy survival (PCS) and time-to-treatment failure (TTF) were
calculated using the Kaplan-Meier method. RESULTS: 18F-FET-PET based response has
shown patients with RD to have the longest TTF time (78.5 vs 24.6 vs 24.1 months,
p = 0.001), while there was no significant difference between patients with a SD
and PD. A comparable pattern was observed for PCS (p < 0.001). T2-volume based
assessment was not associated with outcome. CONCLUSION: 18F-FET-PET is a
promising biomarker for early response assessment in Gd-negative gliomas
undergoing chemotherapy. It might be helpful for a timely adjustment of
potentially ineffective treatment concepts and overcomes limitations of
conventional structural imaging.
PMID- 29948766
TI - Effect of lapatinib on meningioma growth in adults with neurofibromatosis type 2.
AB - INTRODUCTION: Epidermal growth factor receptors EGFR and ErbB2 are overexpressed
in schwannomas and meningiomas. Preclinical and clinical data indicate that
lapatinib, an EGFR/ErbB2 inhibitor, has antitumor activity against vestibular
schwannomas in neurofibromatosis type 2 (NF2) patients. Its antitumor activity
against meningiomas, however, is unknown. METHODS: We conducted a retrospective
review of patients with NF2 and progressive vestibular schwannomas treated on a
phase 2 clinical trial with lapatinib (NCT00973739). We included patients with at
least one volumetrically measurable meningioma (> 0.5 cm3) who received at least
five 28-day courses of treatment. Patients received lapatinib 1500 mg daily.
Meningioma response was assessed using 3-dimensional MRI volumetrics. Progressive
meningioma growth and response were defined as + 20 and - 20% change in tumor
volume from baseline, respectively. Off-treatment was defined as any period > 5
months without lapatinib. RESULTS: Eight patients (ages: 20-58 years) who met
criteria had 17 evaluable meningiomas with a combined volume of 61.35 cc at
baseline, 61.17 cc during treatment, and 108.86 cc (+ 77.44% change) off
treatment, p = 0.0033. Median time on-treatment and off-treatment was 15.5 and
16.7 months, respectively. On-treatment mean and median annualized growth rates
were 10.67 and 1.32%, respectively. Off-treatment mean and median annualized
growth rates were 20.05 and 10.42%, respectively. The best volumetric response
was - 26.1% after 23 months on lapatinib. Two tumors increased > 20%
volumetrically on-treatment, compared to eight tumors off-treatment. CONCLUSIONS:
These data suggest that lapatinib may have growth-inhibitory effects on
meningiomas in NF2 patients, and support prospective studies of lapatinib for NF2
patients with progressive meningiomas.
PMID- 29948769
TI - Widespread disseminated osseous metastases of intracranial meningioma with over
27-year-survivorship: a unique, idiosyncratic case.
PMID- 29948768
TI - Outcome of partially irradiated recurrent nonfunctioning pituitary macroadenoma
by gamma knife radiosurgery.
AB - BACKGROUND: Gamma knife treatment outcome of large pituitary tumors which are
only partially irradiated secondary to immediate proximity to critical structures
such as the optic apparatus have not been rigorously studied. MATERIALS AND
METHODS: From July 2003 to December 2013, there were 41 cases of recurrent or
residual nonfunctioning pituitary macroadenoma partially treated with gamma knife
radiosurgery (GKRS) because the adenoma obscured part of the optic apparatus on
planning SRS MR imaging. RESULTS: The follow up period after GKRS was 92.3 +/-
5.6 months. The percentage of tumor coverage with the full dose was 88.5 +/-
0.7%. Five of 43 (11.6%) patients experienced a transient visional decrease and
one patient experienced a permanent visual field defect. During the follow up,
two patients underwent transphenoidal surgery and one patient had a craniotomy
due to tumor progression. Seven patients (16.2%) developed cortisol and thyroxine
deficiencies. In multiple variant analyses, transient visual decline was
correlated to the tumor volume (> 3.5 cc), percentage of tumor coverage (< 90%),
the distance from the optic apparatus to the pituitary stalk (> 15 mm) and
percentage of tumor above the orbital apex (65%). CONCLUSION: In the limited case
of this cohort, we found that partially treated pituitary nonfunctioning
macroadenoma yielded a high tumor control rate. However, visual decline as a
result of tumor progression or radiation effect can occur in a minority of
patients. The radiosurgical technique warrants further study to better define the
long-term risk to benefit profile for its use in complex pituitary macroadenoma
obscuring part of the optic apparatus.
PMID- 29948767
TI - The utility of routine surveillance screening with magnetic resonance imaging
(MRI) to detect tumour recurrence in children with low-grade central nervous
system (CNS) tumours: a systematic review.
AB - BACKGROUND: Magnetic resonance imaging (MRI) is routinely used as a surveillance
tool to detect early asymptomatic tumour recurrence with a view to improving
patient outcomes. This systematic review aimed to assess its utility in children
with low-grade CNS tumours. METHODS: Using standard systematic review methods,
twelve databases were searched up to January 2017. RESULTS: Seven retrospective
case series studies (n = 370 patients) were included, with average follow-up
ranging from 5.6 to 7 years. No randomised controlled trials (RCTs) were
identified. Due to study heterogeneity only a descriptive synthesis could be
undertaken. Imaging was most frequent in the first year post-surgery (with 2-4
scans) reducing to around half this frequency in year two and annually thereafter
for the duration of follow-up. Diagnostic yield ranged from 0.25 to 2%.
Recurrence rates ranged from 5 to 41%, with most recurrences asymptomatic (range
65-100%). Collectively, 56% of recurrences had occurred within the first year
post-treatment (46% in the first 6-months), 68% by year two and 90% by year five.
Following recurrence, 90% of patients underwent treatment changes, mainly repeat
surgery (72%). Five-year OS ranged from 96 to 100%, while five-year recurrence
free survival ranged from 67 to 100%. None of the studies reported quality of
life measures. CONCLUSION: This systematic review highlights the paucity of
evidence currently available to assess the utility of MRI surveillance despite it
being routine clinical practice and costly to patients, their families and
healthcare systems. This needs to be evaluated within the context of an RCT.
PMID- 29948770
TI - Effect of Rufinamide on the kainic acid-induced excitotoxic neuronal death in the
mouse hippocampus.
AB - Rufinamide (RUF) is a structurally unique anti-epileptic drug, used in the
treatment of seizure disorders such as Lennox-Gastaut syndrome. In the present
study, we investigated whether RUF protected against excitotoxic neuronal damage
in the mouse hippocampal CA3 region after intraperitoneal kainic acid (KA)
injection. Treatment with 25, 50 and 100 mg/kg RUF significantly decreased the KA
induced neuronal death in the hippocampal CA3 region in a dose-dependent manner.
In addition, 100 mg/kg RUF treatment reduced the KA-induced oxidative stress
related increase of MDA level and decrease of total SOD activity in the
hippocampus. KA-induced increases of pro-inflammatory cytokines, TNF-alpha and IL
1beta, levels as well as KA-induced microglial activation were also suppressed by
RUF treatment. These results indicate that RUF displays a neuroprotective effect
against KA-induced excitotoxic neuronal death in the mouse hippocampus through
anti-oxidant and anti-inflammatory activities.
PMID- 29948771
TI - Two new naphthalenic lactone glycosides from Cassia obtusifolia L. seeds.
AB - Two new naphthalenic lactone glycosides, (3S)-9,10-dihydroxy-7-methoxy-3-methyl-1
oxo-3,4-dihydro-1H-benzo[g]isochromene-3-carboxylic acid 9-O-beta-D
glucopyranoside (1) and (3R)-cassialactone 9-O-beta-D-glucopyranoside (2) were
isolated from seeds of Cassia obtusifolia Linn., along with five known compounds:
(3R)-cassialactone 9-O-beta-D-gentiobioside (3), emodin 1-O-beta-gentiobioside
(4), 1-hydroxyl-2-acetyl-3,8-dimethoxy-naphthalene 6-O-beta-D-apiofuranosyl-(1 ->
2)-beta-D-glucopyranoside (5), rubrofusarin 6-O-beta-D-gentiobioside (6),
rubrofusarin 6-O-beta-D-triglucoside (7). Structures of 1 and 2 were elucidated
by NMR and HR-ESI-MS spectroscopic analysis. Their stereochemistry was determined
by CD experiment. All compounds were tested for their ability to inhibit the
formation of advanced glycation end-products in vitro. Compounds 1, 2, 3, 5, and
6 showed significant in vitro inhibitory activities (IC50 values of 11.63, 23.40,
7.32, 89.03, and 38.89 uM, respectively).
PMID- 29948772
TI - Effect of thiazolidinedione phenylacetate derivatives on wound-healing activity.
AB - The aim of this work was to evaluate the synthesis and structure-activity
relationship of 4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl 2-phenylacetate
derivatives as potential wound-healing agents. The IC50 values of the lead
compounds ranged from 0.01 to 0.05 uM. These compounds also increased the levels
of extracellular prostaglandin E2 (PGE2) in A549 cells. Among the synthesized
compounds, compounds 66, 67, 69, and 86 increased PGE2 levels 3- to 4-fold of
those achieved with the negative control. Introduction of a halogen at the
intermediate phenyl ring, compounds 66, 67, 69, and 86 resulted in higher IC50
values, which indicated lower cytotoxicity than that observed upon the
introduction of other substituents at the same position. In particular, cells
exposed to compound 69 showed significantly improved wound healing, and the wound
closure rate achieved was approximately 3.2-fold higher than that of the control.
Therefore, compound 69 can be used for tissue regeneration and treatment of
diverse diseases caused by PGE2 deficiency. Overall, our findings suggested that
compound 69 might be a novel candidate for skin wound therapy.
PMID- 29948773
TI - Effects of heat stress on piglet production/performance parameters.
AB - Heat stress is problematic for pigs raised in tropical environments. The animal
is large and has proportionally high body heat, and subcutaneous fat thickness
reduces the animal's ability to thermoregulate. It is not clear how stress
affects pig litter size. For this reason, we performed a meta-analysis of the
effect of heat stress on pig litter size. We reviewed behavioral, endocrine, and
cellular data and the signaling pathways involved in heat stress. We found that
heat stress did not affect litter size or the body weight of offspring. However,
heat stress was found to decrease litter body weight gain due to reductions in
sow milk production. For this reason, artificial feeding of piglets may be
appropriate.
PMID- 29948774
TI - Diagnosis of bovine mastitis: from laboratory to farm.
AB - Accurate diagnosis of disease is the major step between the cause and cure of
disease. An economical, reliable, and rapid diagnostic tool is fundamental for
the management of udder health. The earlier the disease is identified, the less
will be the damage; keeping this in mind, many efforts are being made to develop
reliable diagnostic tools for use on farm. However, traditional gold standard
methods including somatic cell count and microbial culturing are still in use.
They are partially being replaced with polymerase chain reaction and sequencing
based tests. Nanotechnology and protein-based tests have also gained lot of
attention and some of them are potential candidate of future diagnostic tests for
bovine mastitis. Research laboratories are struggling to develop simple,
economical, and user-friendly biosensor-based methods that can be performed on
farm for rapid diagnosis. The combination of both genomic and proteomic
approaches, together with further involvement of nanotheranostic technologies and
other sensors, will assist in the quest of better mastitis diagnostic tools.
PMID- 29948775
TI - Milk production and fatty acid profile of dairy cows grazing four grass species
pastures during the rainy season in small-scale dairy systems in the highlands of
Mexico.
AB - The study evaluated small-scale dairy systems with continuous grazing of pastures
based on three temperate grasses festulolium (FL), tall fescue (TF), and
perennial ryegrass (RG), compared with subtropical kikuyu grass (KG). All
pastures were associated with white clover (Trifolium repens L.). Twelve
multiparous Holstein cows were assigned to a 4 * 4 Latin square replicated three
times with 14-day experimental periods. Sampling and analyses of pastures,
concentrates, and animal variables followed standard procedures. FL showed a
significantly (p < 0.05) higher mean sward height, but there were no differences
(p > 0.05) in net herbage accumulation. There were significant differences (p <
0.05) among pastures for CP, NDF, ADF, in vitro digestibility of OM (IVOMD), and
estimated metabolizable energy (eME). There were no differences (p > 0.05)
between treatments for milk yield and composition, live weight, or body condition
score. There were significant differences (p < 0.05) in fatty acid values for
pastures in C14:0, C16:1, and C18:3n3. There were significant differences between
treatments (p < 0.05) in milk contents for C18:0, C18:1t11, and C18:2c9t11.
Grazing FL, TF, RG, or KY pastures showed no differences in milk yields. Higher
values for C18:0, C18:1t11, and C18:2c9t11 were detected in KY, RG, and TF. RG
had significantly higher MUFA than FL and higher PUFA than TF. A value under 65%
of SFA, a ratio of n-6/n-3 lower than 4, and an atherogenic index of 1.7 are
indicators of milk with beneficial effects for human health.
PMID- 29948776
TI - Seroprevalence of bovine brucellosis and associated risk factors in Nakasongola
district, Uganda.
AB - A cross-sectional study was carried out between November 2015 and January 2016 to
determine the seroprevalence of Brucella antibodies in cattle raised under
communal, fenced farms and tethering systems and the associated factors. Seven
hundred twenty-eight bovine sera were collected and tested with rose Bengal test
as a screening test and the indirect enzyme-linked immunosorbent assay as a
confirmatory test. Animal- and herd-level data were collected and binary logistic
regression was used to assess the potential risk factors. True animal- and herd
level prevalence was highest in the fenced farms (4.5% (95%CI, 2.3-6.9) and 19.5%
(95%CI, 8.2-32.7) respectively). The risks for natural brucellosis infection were
sharing water with wild animals (OR = 0.21, 95%CI, 0.104-0.83), herd size
(medium: OR = 0.089, 95%CI 0.017-0.449; large: OR = 0.024, 95%CI 0.003-0.203),
fenced farms (OR = 3.7, 95% CI, 1.7-7.9), sex (OR = 0.03, 95%CI, 0.01-0.079), and
lactation (OR = 0.013, 95%CI, 0.004-0.049). Changes in rangeland tenure and the
shift towards intensive cattle production have influenced brucellosis
epidemiology. Future studies should aim at identifying the infecting Brucellae
and examining the role of wildlife in brucellosis epidemiology.
PMID- 29948777
TI - Phylogenetic analysis of the lumpy skin disease viruses in northwest of Iran.
AB - Lumpy skin disease (LSD) is a devastating viral disease of cattle which has
recently spread from Africa into the countries of the Middle East. The aim of the
present study was to investigate the relationships among lumpy skin disease
viruses (LSDV) isolated from different regions of Iran and the origin and spread
of these viruses. In this study, a total of 234 blood samples from clinically
affected animals from four provinces in the northwest of Iran were screened for
LSDV using polymerase chain reaction (PCR). From 80 positive samples for LSDV
detected by PCR, the partial P32 gene (759 bp) of 12 isolates were sequenced and
phylogenetically analyzed. LSD viruses were grouped in three subclusters with an
overall 97.1-100% nucleotide identity. LSDVs isolated from Gilan showed lowest
nucleotide identity with the other LSDVs. Four isolates of LSDV including KO-1,
EA-1, EA-3, and WA-3 showed 100% similarity with each other and also with the
Neethling strain. Phylogenetic analysis indicated that the identified LSDVs were
closely related to each other and had high-sequence homology with other LSDV
isolates from Africa. It was concluded that LSD outbreak probably occurred in the
northwest of Iran by LSDVs entering the country from Iraq and P32 nucleotide
sequence information obtained in the present study is a valuable resource in
understanding the genetic nature and molecular epidemiology of local LSDV
isolates which can be used for future vaccine development based on the
circulating strains in the region.
PMID- 29948778
TI - Effect of corn supplementation on purine derivatives and rumen fermentation in
sheep fed PKC and urea-treated rice straw.
AB - This study investigated the effect of different levels of corn supplementation as
energy source into palm kernel cake-urea-treated rice straw basal diet on urinary
excretion of purine derivatives, nitrogen utilization, rumen fermentation, and
rumen microorganism populations. Twenty-seven Dorper lambs were randomly assigned
to three treatment groups and kept in individual pens for a 120-day period. The
animals were subjected to the dietary treatments as follows: T1: 75.3% PKC + 0%
corn, T2: 70.3% PKC + 5% corn, and T3: 65.3% PKC + 10% corn. Hypoxanthine and
uric acid excretion level were recorded similarly in lambs supplemented with
corn. The microbial N yield and butyrate level was higher in corn-supplemented
group, but fecal N excretion, T3 has the lowest level than other groups. Lambs
fed T3 had a greater rumen protozoa population while the number of R.
flavefaciens was recorded highest in T2. No significant differences were observed
for total bacteria, F. succinogenes, R. albus, and methanogen population among
all treatment. Based on these results, T3 could be fed to lambs without
deleterious effect on the VFA and N balance.
PMID- 29948779
TI - Octreotide Use in Neonates: A Case Series.
AB - BACKGROUND AND OBJECTIVE: Octreotide is a somatostatin analogue and has been used
off-label for a variety of conditions. There are no specific guidelines for the
use of octreotide in neonates and its safety and efficacy have not been
systematically evaluated. The objective of this study is to present our
experience of using octreotide therapy in neonates. METHODS: This is a
retrospective study of neonates who received octreotide therapy during their
hospital stay over a 15 years period (2003-2017) in a tertiary neonatal centre.
The demographic details and indications of octreotide therapy including time of
initiation, route, dose, duration and adverse effects of therapy were noted. The
clinical course following octreotide administration was also analysed. RESULTS:
Eleven neonates received octreotide therapy during the study period, of which
nine had chylothorax and two had chylous ascites. Resolution of the chylous
effusion with octreotide therapy was achieved in 4 out of 11 (36.3%) of the
cases. The median duration of octreotide therapy in cases with successful
resolution was 17.5 days. With the exception of minor side effects such as
hyperglycaemia, none of the patients had any significant side effects that
required discontinuation of therapy. CONCLUSION: Octreotide was used safely as an
adjunctive therapy for the treatment of chylothorax and chylous ascites in
neonates. However, larger prospective controlled trials are required to establish
the optimal dose, time of initiation, duration and efficacy of octreotide therapy
in neonates.
PMID- 29948780
TI - Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer
Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter,
Retrospective Analysis by the MITO Group (MITO 24).
AB - BACKGROUND: The variability in progression-free survival (PFS) and overall
survival (OS) among patients with epithelial ovarian cancer (EOC) makes it
difficult to reliably predict outcomes. A predictive biomarker of bevacizumab
efficacy as first-line therapy in EOC is still lacking. OBJECTIVE: The MITO group
conducted a multicenter, retrospective study (MITO 24) to investigate the role of
inflammatory indexes as prognostic factors and predictors of treatment efficacy
in FIGO stage III-IV EOC patients treated with first-line chemotherapy alone or
in combination with bevacizumab. PATIENTS AND METHODS: Of the 375 patients
recruited, 301 received chemotherapy alone and 74 received chemotherapy with
bevacizumab. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to
lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were
evaluated to identify a potential correlation with PFS and OS in both the overall
population and the two treatment arms. RESULTS: In the overall population, the
PFS and OS were significantly longer in patients with low inflammatory indexes (p
< 0.0001). In multivariate analyses, the NLR was significantly associated with OS
(p = 0.016), and the PLR was significantly associated with PFS (p = 0.024).
Inflammatory indexes were significantly correlated with patient prognosis in the
chemotherapy-alone group (p < 0.0001). Patients in the chemotherapy with
bevacizumab group with a high NLR had a higher PFS and OS (p = 0.026 and p =
0.029, respectively) than those in the chemotherapy-alone group. Conversely, PFS
and OS were significantly poorer in patients with a high SII (p = 0.024 and p =
0.017, respectively). CONCLUSION: Our results suggest that bevacizumab improves
clinical outcome in patients with a high NLR but may be detrimental in those with
a high SII.
PMID- 29948781
TI - First detection and full genome sequence of porcine circovirus type 3 in Russia.
AB - Porcine circovirus type 3 (PCV3) was firstly detected in 2016 in USA. Later PCV3
was discovered in Asia, Europe, and South America. The present investigation
demonstrates for the first time the circulation of PCV3 among pigs in Russia. The
viruses were detected at two geographically distant unrelated commercial farms
with records of reproductive failure (abortions, stillbirth), porcine dermatitis,
and nephropathy syndrome (PDNS). The two farms were located in the region of
Smolensk (western part of Russia) and the region of Tyumen (West Siberia,
Russia). We investigated samples collected from pigs of different ages. We
performed PCR for the PCV3 DNA detection. The DNA of PCV3 was detected in serum,
kidney, heart, spleen, pleural effusion, and peritoneal cavity fluid samples. Two
viral genomes were sequenced and the corresponding strains were named PCV3
RU/SM17 (the strain from Smolensk region) and PCV3-RU/TY17 (the strain from
Tyumen region). The full genome sequences of both strains were 2000 nucleotides
in length and contained at least two ORFs, encoding the Cap and Rep proteins.
Full sequence alignment revealed a 99.3% identity between the PCV3-RU/SM17 and
PCV3-RU/TY17 strains. Molecular analysis showed that the two strains from Russia
are highly homologous to viruses identified in other countries, with a 98.5-99.6%
homology for PCV3-RU/TY17 and 97.9-99.0 for PCV3-RU/SM17. The PCV3-RU/SM17 and
PCV3-RU/TY17 strains were found to form a monophyletic group in a phylogenetic
tree based on PCV3 complete genome sequences.
PMID- 29948783
TI - Avenues of Influence: the Relationship between Health Impact Assessment and
Determinants of Health and Health Equity.
AB - This study aims to identify perceived impacts of Health Impact Assessment (HIA)
on decision-making, determinants of health, and determinants of health equity and
outline the mechanisms through which these impacts can occur. The research team
conducted a mixed-methods study of HIAs in the USA. First, investigators
collected data regarding perceived HIA impacts through an online questionnaire,
which was completed by 149 stakeholders representing 126 unique HIAs. To explore
in greater depth the themes that arose from the online survey, investigators
conducted semi-structured interviews with 46 stakeholders involved with 27 HIAs
related to the built environment. This preliminary study suggests that HIAs can
strengthen relationships and build trust between community and government
institutions. In addition, this study suggests that HIA recommendations can
inform policy and decision-making systems that determine the distribution of
health-promoting resources and health risks. HIA outcomes may in turn lead to
more equitable access to health resources and reduce exposure to environmental
harms among at-risk populations. Future research should further explore
associations between HIAs and changes in determinants of health and health equity
by corroborating findings with other data sources and documenting potential
impacts and outcomes of HIAs in other sectors.
PMID- 29948782
TI - Sec13 is a positive regulator of VISA-mediated antiviral signaling.
AB - Viral infection triggers the innate antiviral immune response that rapidly
produces type I interferons in most cell types to combat viruses invading. Upon
viral infection, the cytoplasmic RNA sensors RIG-I/MDA5 recognize viral RNA, and
then RIG-I/MDA5 is transported to mitochondria interacting with VISA through the
CARD domain. From there, VISA recruits downstream antiviral signaling pathways
molecules, such as TRAFs and TBK1. Eventually, IRF3 is phosphorylated and type I
IFNs are induced to fight as the first line of defense against viruses. However,
it remains unclear how VISA acts as a scaffold to assemble the signalosome in RIG
I-mediated antiviral signaling. Here, we demonstrated Sec13 as a novel component
that was involved in VISA-mediated antiviral signaling pathway. The co
immunoprecipitation assays showed that Sec13 specifically interacts with VISA.
Overexpression of Sec13 increases VISA's aggregation and ubiquitination and
significantly enhances the phosphorylation and dimerization of IRF3, facilitating
the IFN-beta production. Conversely, the knockdown of Sec13 attenuates Sendai
virus-induced and VISA-mediated IRF3 activation and the production of IFNbeta,
thus weakens antiviral immune activity.
PMID- 29948784
TI - Men in Community Correction Programs and Their Female Primary Sex Partners:
Latent Class Analysis to Identify the Relationship of Clusters of Drug Use and
Sexual Behaviors and HIV Risks.
AB - Existing research indicates that justice-involved individuals use a variety of
different drugs and polysubstance use is common. Research shows that different
typologies of drug users, such as polydrug users versus users of a single drug,
have differing types of individual-, structural-, and neighborhood-level risk
characteristics. However, little research has been conducted on how different
typologies of drug use are associated with HIV risks among individuals in
community corrections and their intimate sex partners. This paper examines the
different types of drug use typologies among men in community correction programs
and their female primary sex partners. We used latent class analysis to identify
typologies of drug use among men in community correction programs in New York
City and among their female primary sex partners. We also examined the
associations between drug use typologies with sexual and drug use behaviors that
increase the risk of HIV acquisition. The final analysis included a total of 1167
participants (822 male participants and 345 of their female primary sex
partners). Latent class analyses identified three identical typologies of drug
use for both men and their female primary sex partners: (1) polydrug use, (2)
mild polydrug users with severe alcohol and marijuana use, and (3) alcohol and
marijuana users. Men and women who were classified as polydrug users and mild
polydrug users, compared to those who were classified as alcohol and marijuana
users, tended to be older and non-Hispanic Caucasians. Polydrug users and mild
polydrug users were also more likely to have risky sex partners and higher rates
of criminal justice involvement. There is a need to provide HIV and drug use
treatment and linkage to service and care for men in community correction
programs, especially polydrug users. Community correction programs could be the
venue to provide better access by reaching out to this high HIV risk key
population with increased rates of drug use and multiple sex partners.
PMID- 29948785
TI - Talking the Walk: Perceptions of Neighborhood Characteristics from Users of Open
Streets Programs in Latin America and the USA.
AB - Physical inactivity is estimated to be the fourth leading cause of global
mortality. Strategies to increase physical activity (PA) increasingly emphasize
environmental and policy changes including the modification of neighborhood
environments to promote walking and other forms of healthy activity. Open Streets
(OS) initiatives, an important and growing strategy to modify neighborhood
environments for PA, create temporary parks for recreational activity by closing
streets to motor vehicle traffic, thereby offering health and community building
benefits. We used the Stanford Neighborhood Discovery Tool (DT)-photo/voice
software on a tablet-to train neighborhood residents to act as "citizen
scientist" observers of the local built environment on a non-event day and during
an OS initiative. The purposes of this project were as follows: (1) to assess
adult residents' perceptions of neighborhood characteristics of the OS initiative
in three socioeconomically diverse sites and (2) to test the DT for use in three
international urban settings with OS initiatives; Bogota, Colombia; San
Francisco, USA; and Temuco, Chile, among a multigenerational, multiethnic sample
of adults including, for the first time, a vulnerable population of homeless
adults (Bogota). Using the DT, participants walked an OS route taking photos and
recording reasons for the photos, then completed a 25-item
demographic/environmental observation survey and a 16-item Reflection Survey on
perceived environmental changes. A total of 18 themes were reported by
participants with areas of overlapping themes (e.g., Community and Social
Connectedness) and areas where a single site reported a theme (e.g., Social
Isolation in Older Adults). Ten of the 18 themes were identified by at least two
sites including "Bike Resources" and "Services", indicating the value of
programming at OS initiatives. The themes of "Festive Environment" and "Family
Friendly Environment" reflect the quality of the overall environment for
participants. Four themes (Community and Social Connectedness, Family Friendly
Environment, PA, and Safety) were reported by all sites. Three of the four
unifying themes were also ranked among the highest reported categories of "seemed
better" on the Reflection Survey (Ease of Walking, Overall Safety of
Neighborhood, and Friendliness of Environment), providing additional confirmation
of the shared experience of social, health, and psychological benefits from OS
initiatives. OS initiatives offer a global strategy for increasing neighborhood
opportunities for PA and a potential site for training citizen scientists to
document environmental influences on PA.
PMID- 29948787
TI - Consciousness as an Inhibited Manifestation and Quantum Physics.
AB - The term soul is used in the traditional literature as a synonym for one's true
Self and is associated with the subjective essence of one's living. Since, we
don't have any means to quantify it, the science has ruled out this idea from its
investigations. But, in a recent study, Ceylan et al. (2017) has reintroduced the
word soul to scientific literature and examined the possibility of the study of
the soul through scientific modalities. The primary focus of their study is to
find and understand the scientific analog of the soul as quoted and discussed in
the traditional literature. In the present paper, we examine the idea of a soul
that uses a novel approach; integrating neuroscience and quantum physics, as
proposed in Ceylan et al. (2017). For this purpose, we make use of findings from
neuroscientific studies on meditation to understand the concepts of soul and
consciousness in terms of inhibition mechanisms. In this context, this paper
serves as an attempt to call for more studies to discuss and expand the
hypothesis about the soul as uninhibited mental activity.
PMID- 29948786
TI - FPS-ZM1 and valsartan combination protects better against glomerular filtration
barrier damage in streptozotocin-induced diabetic rats.
AB - Despite the effectiveness of renin-angiotensin blockade in retarding diabetic
nephropathy progression, a considerable number of patients still develop end
stage renal disease. The present investigation aims to evaluate the protective
potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation
end products (RAGE), alone and in combination with valsartan, an angiotensin
receptor blocker, against glomerular injury parameters in streptozotocin-induced
diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and
their combination were administered for 4 weeks, starting 2 months after diabetes
induction in rats. Tests for kidney function, glomerular filtration barrier, and
podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan
attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated
NF-kappaB p65 subunit. It ameliorated glomerular injury due to diabetes by
increasing glomerular nephrin and synaptopodin expressions, mitigating renal
integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type
IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated
by decreasing levels of serum cystatin C. Additionally, the combination also
alleviated indices of renal inflammation as revealed by decreased renal monocyte
chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12)
expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and
urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the
benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury
evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential
adjunct to the conventional renin-angiotensin blockade.
PMID- 29948788
TI - The Issue of Schooling....or How to Tame a Horse.
AB - The issue of schooling is being thoroughly analysed by a number of excellent
scholars in this special issue. It is a very comprehensive analytical work which
I intend to take into a commentary consideration in this brief article. Schooling
is a matter of great and recent concern not the least from a political point of
view, where schooling seems to take on a specific role that deals with not only
schooling as a normativity but also schooling as the absolute forming of
students. Despite ongoing disagreements on what kind of schooling may prove the
best as well as the correct form of education as a whole, in this paper I argue
that relevant science may have a pretty good idea as to how to apply schooling in
such a way as to ensure that teaching is applied equally efficient. It is,
however, slightly more difficult to see how this very same science and the above
mentioned knowledge finds its way into educational policies not to mention
finding its way into the classroom. I argue, that schooling is not (surprisingly
and not only) society's tool for data delivery and data interpretation, but also
(and perhaps rather) some certain specific actors of society's tool for
culturalization. This thereby changes schooling from being an educational tool
only, a mere transfer of data and a formation of students into a political tool,
thus creating a notion of schooling being more or less synonymous with a
different kind of formation, a formation of a quite specific nature to suit quite
specific properties. I claim these properties to be of an economic, market
oriented and universalist nature. I therefore wish to draw attention to two
aspects of interest: the oddity of science's position in this matter, where
science appears to have plausible answers as to how the best possible schooling
looks like, however, at the same time - not surprisingly - also seem to live up
to politically phrased demands in accordance with the premise of the competition
state. This, off course, give rise to further questions on the necessity of
politically independent universities and the pressure they underlie.
PMID- 29948789
TI - Opinions and Expectations of Muslim Donors' Relatives Deciding Organ Donation:
The Sample of Istanbul.
AB - The low rate of consent by relatives of potential donors especially in Muslim
majority countries is one of the basic limiting factors of the success of organ
transplantation. Therefore, this study aimed to explore opinions and expectations
of relatives after donating their beloved ones' organs on a Muslim sample in
Istanbul Region. Descriptive method was used. Data were collected from 82 of 95
Muslim donor relatives who agreed to participate in the study between the March
and July 2014 via telephone calls. It was found that most of the relatives had
donated the organs of their relatives for "keeping alive the beloved ones' organs
in others' bodies instead to send them to the soil." Less of the relatives
expressed regret for donating due to not introducing to the recipients. Muslim
donor families also expect priority in hospitals and priority for transplantation
if they have another relative waiting for organ transplantation.
PMID- 29948790
TI - Health Promotion Needs in Faith-Based Organizations: Perceptions of Religious
Leaders in Bamako.
AB - The purpose of this study was to explore imams' and pastors' perspectives of the
health promotion needs of congregants in Bamako, Mali and to examine the physical
environment for health promotion in faith-based organizations' (FBOs). In-depth
one-on-one interviews were conducted with imams (n = 10) and pastors (n = 2) as
well as observations of the physical environment in FBOs in Bamako, Mali. Data
were analyzed using a content analysis approach guided by the social ecological
model. Leaders frequently mentioned poverty and affordability as challenges
perceived by congregants but congregants support each other with financial
contributions. The main challenge mentioned was a lack of knowledge among leaders
(primarily imams) about health and health programs.
PMID- 29948791
TI - Impact of Hajj on Global Health Security.
AB - With the human society transfers from scattered pieces to a society as a whole
and the advent of the aviation era, the occurrence of infectious diseases and
their diffusion have led to international health security issues. As the world's
largest and irrevocable annual transnational religious movement, the Hajj and its
connection with health security concerns have caught attention since the ancient
times, because a huge population from all over the world gathers in the holy city
of Mecca, which has tropical arid climate. Currently, the international community
and international organizations are implementing multilevel governance with
respect to the health security issues of the Hajj. Relevant agencies include the
World Health Organization and its regional branches, International Red Cross and
Red Crescent Movement (ICRC), the Ministry of Hajj as well as the Ministry of
Health of Saudi Arabia, and the public health sectors/agencies in various
countries that are involved with Hajj activities. The international community has
successfully held the Hajj events, even when facing the challenges brought by
some viral respiratory diseases such as SARS and MERS. The Hajj has become a rare
opportunity for all stakeholders to improve their capabilities in international
health security governance.
PMID- 29948792
TI - Islam and Motivation to Quit Smoking: Public Health Policy Implications.
AB - In the WHO Eastern Mediterranean Regional Office some 14 years ago, a
'religiously inspired approach' was proposed to combat tobacco use. This promoted
a useful debate in the region. The purpose of this paper is to argue the need to
identify the role which Islamic beliefs and teachings play (1) in influencing
individual motivation to quit smoking and (2) in gaining support for public
policies to reduce smoking. Ramadan and Hajj are taken as key points. These, it
is argued, are times when Muslim religious motivation to abstain from smoking is
strongest. This paper concludes that there is an insufficient evidence base on
which to adopt a religiously inspired approach. All of civil society, including
religious Muslim authorities, should rather supplement the efforts of health
professionals to encourage smoking cessation.
PMID- 29948793
TI - Religion, Culture and Meaning-Making Coping: A Study Among Cancer Patients in
Malaysia.
AB - The present study aimed to explore the use of meaning-making coping mechanisms
(existential, spiritual and religious coping) among ethnic Malay cancer patients
in Malaysia and to investigate the impact of culture on their choice of coping
methods. Twenty-nine participants with various kinds of cancer were interviewed.
Four kinds of coping resources emerged from analyses of the interview
transcripts: (1) relying on transcendent power, (2) supernatural or mystical
beliefs, (3) finding oneself in relationships with others and (4) nature. In this
article, the two first resources are in focus. The present findings suggest that
Malay culture, which is imbued with Islamic belief, strongly influences cancer
patients' coping methods and ways of looking at their experience of being cancer
patients.
PMID- 29948794
TI - Reduced and optimized trial designs for drugs described by a target mediated drug
disposition model.
AB - Monoclonal antibodies against soluble targets are often rich and include the
sampling of multiple analytes over a lengthy period of time. Predictive models
built on data obtained in such studies can be useful in all drug development
phases. If adequate model predictions can be maintained with a reduced design
(e.g. fewer samples or shorter duration) the use of such designs may be
advocated. The effect of reducing and optimizing a rich design based on a
published study for Omalizumab (OMA) was evaluated as an example. OMA
pharmacokinetics were characterized using a target-mediated drug disposition
model considering the binding of OMA to free IgE and the subsequent formation of
an OMA-IgE complex. The performance of the reduced and optimized designs was
evaluated with respect to: efficiency, parameter uncertainty and predictions of
free target. It was possible to reduce the number of samples in the study by 30%
while still maintaining an efficiency of almost 90%. A reduction in sampling
duration by two-thirds resulted in an efficiency of 75%. Omission of any analyte
measurement or a reduction of the number of dose levels was detrimental to the
efficiency of the designs (efficiency <= 51%). However, other metrics were, in
some cases, relatively unaffected, showing that multiple metrics may be needed to
obtain balanced assessments of design performance.
PMID- 29948796
TI - The conversion to Rastelli's type operation from Patrick-McGoon's procedure of an
adult with Taussig-Bing heart: a case report.
AB - A 23-year-old female of Taussig-Bing heart with antero-posterior relation of the
great arteries was underwent Patrick-McGoon's intraventricular rerouting at 6
years old of age. The left ventricular outflow obstruction (peak pressure
gradient of 100 mmHg) developed, and severe aortic valve regurgitation following
bacterial endocarditis was noted. The conversion to Rastelli's type operation and
aortic valve replacement were performed successfully at 23 years old of age. She
is doing well without any significant left or right ventricular outflow
obstruction at 7 years postoperatively.
PMID- 29948795
TI - Modeling and simulations to support dose selection for eslicarbazepine acetate
therapy in pediatric patients with partial-onset seizures.
AB - Modeling and simulations were used to support body weight-based dose selection
for eslicarbazepine acetate (ESL) in pediatric subjects aged 4-17 years with
partial-onset seizures. A one-compartment pediatric population pharmacokinetic
model with formulation-specific first-order absorption, first-order elimination,
and weight-based allometric scaling of clearance and distribution volume was
developed with PK data from subjects 2-18 years of age treated with ESL 5-30
mg/kg/day. Covariate analysis was performed to quantify the effects of key
demographic and clinical covariates (including body weight and concomitant use of
carbamazepine, levetiracetam, and phenobarbital-like antiepileptic drugs [AEDs])
on variability in PK parameters. Model evaluation performed using a simulation
based visual predictive check and a non-parametric bootstrap procedure indicated
no substantial bias in the overall model and in the accuracy of estimates. The
model estimated that concomitant use of carbamazepine or phenobarbital-like AEDs
with ESL would decrease the exposure of eslicarbazepine, and that concomitant use
of levetiracetam with ESL would increase the exposure of eslicarbazepine,
although the small effect of levetiracetam may not represent a true difference.
Model-based simulations were subsequently performed to apply target exposure
matching of selected ESL doses for pediatric subjects (aged 4-17 years) to attain
eslicarbazepine exposures associated with effective and well-tolerated ESL doses
in adults. Overall, model-based exposure matching allowed for extrapolation of
efficacy to support pediatric dose selection as part of the submission to obtain
FDA approval for ESL (adjunctive therapy and monotherapy) in subjects aged 4-17
years, without requiring an additional clinical study.
PMID- 29948798
TI - Kefir Accelerates Burn Wound Healing Through Inducing Fibroblast Cell Migration
In Vitro and Modulating the Expression of IL-1beta, TGF-beta1, and bFGF Genes In
Vivo.
AB - Kefir is a natural probiotic compound with a long history of health benefits
which can improve wound healing. This study investigated the regeneration
potential of kefir in vitro scratch assay and in vivo burn wound in rat model.
Cytotoxicity of different concentrations of kefir was evaluated by colorimetric
methylthiazoltetrazolium assay. A scratch wound experiment was performed to
investigate the ability of kefir in reducing the gap of wounds in a dose
dependent manner, in vitro. The standardized kefir was incorporated into silver
sulfadiazine (SSD) and applied on burn wounds in vivo, and was compared with the
SSD and negative control groups after 7, 14, and 28 days of treatment. The wound
sites were then removed for histopathological and morphometric analyses,
assessment of interleukin-1beta (IL-1beta), transforming growth factor-beta1 (TGF
beta1), basic fibroblast growth factor (bFGF), dry weight, and hydroxyproline
contents. Kefir enhanced proliferation and migration of human dermal fibroblast
(HDF) cells and 12.50, 6.25, and 3.12 MUL/mL concentrations showed better effects
on the scratch assay. Kefir resulted in reduction of IL-1beta and TGF-beta1
expression at day 7 compared to the negative control. Kefir also reduced the
expression of IL-1beta at days 14 and 28 and stimulated bFGF at day 28. It
significantly improved the dry matter and hydroxyproline contents in the burn
wounds. Kefir also resulted in enhanced angiogenesis and elevated migration and
proliferation of fibroblasts and improved fibrous connective tissue formation in
the wound area. The morphometric results indicated significant global contraction
values in the kefir-treated wounds compared to other groups. Taken together, the
findings suggest that kefir has considerable ability to accelerate healing of the
burn wounds. Therefore, kefir may be a possible option to improve the outcomes of
severe burns.
PMID- 29948797
TI - Acute ischemic stroke as a complication of Stanford type A acute aortic
dissection: a review and proposed clinical recommendations for urgent diagnosis.
AB - BACKGROUND: Stanford type A acute aortic dissection requires emergency surgery.
Because patients with ischemic stroke as a complication of Stanford type A acute
aortic dissection do not often complain of chest or back pain, probably due to
consciousness disturbance, amnesia, or aphasia, a fatal course following
inappropriate intravenous rt-PA therapy and delay of appropriate surgical
treatment sometimes occur. REVIEW AND PROPOSED RECOMMENDATIONS: When treating any
suspected stroke patients, emergency services and initial urgent care doctors
should always suspect aortic dissection. Even in the absence of chest or back
pain, the initial urgent care doctor needs to immediately perform chest contrast
CT if suspecting aortic dissection from blood pressure laterality or upper
mediastinal widening on chest X-ray. Whenever aortic dissection cannot be ruled
out from initial clinical information, the initial urgent care doctor should
evaluate the common carotid artery (CCA). Dissection extension to the CCA or flow
abnormality of the CCA is often detected if aortic dissection is a cause of
ischemic stroke or transient ischemic attack. Head CT or MRI including vascular
imaging is preferable. D-dimer should be measured in hospitals where available.
As soon as aortic dissection is identified, the initial urgent care doctor needs
to consult with cardiovascular surgeons or cardiologists for appropriate
treatment.
PMID- 29948799
TI - Effects of the Dietary Probiotic, Enterococcus faecium NCIMB11181, on the
Intestinal Barrier and System Immune Status in Escherichia coli O78-Challenged
Broiler Chickens.
AB - The effects of Enterococcus faecium on growth, intestinal barrier function, and
immune response in Escherichia coli O78-challenged broiler chickens were
investigated. Three hundred eight 1-day-old Ross male chickens were randomly
assigned into three treatment groups: negative control (C), E. coli O78-infected
positive (EP), and E. coli O78-infected with 200 mg/kg E. faecium dietary
supplementation (EF). E. faecium significantly increased the body weight on day
10 (P < 0.05) and day 15. Furthermore, these birds had a greater average daily
gain compared with the other groups during days 1-10 (P < 0.05). The death rate
of the EF chickens dramatically declined. E. faecium supplementation improved the
jejunal villus height and the ratio of villus height to crypt depth (P < 0.05) 3
and 7 days post-infection. The mRNA expression of claudin-1 significantly
increased by E. faecium (P < 0.05) 3 and 7 days post-infection, and Mucin2 was
markedly enhanced (P < 0.05) 3 days post-infection. E. faecium upregulated the
mRNA expression of PPAR-gamma and IL-10 (P < 0.05) and downregulated that of NF
kappaB, TLR4, and IL-1beta (P < 0.05) in the spleen 3 and 7 days post-infection.
Lipopolysaccharide stimulation index was markedly enhanced in the EF group (P <
0.05) 3 days post-infection. The increased liver E. coli number caused by the E.
coli O78 challenge was significantly reversed by E. faecium (P < 0.05). E.
faecium improved growth and reduced the death rate by regulating the immune
response and maintaining the intestinal integrity in E. coli O78-challenged
broiler chickens.
PMID- 29948800
TI - "Thinking Time": Doctor Envies Curlers.
PMID- 29948801
TI - Multi- and Single-Year High-Utilizers of Inpatient Services Share Many Clinical
and Behavioral Characteristics.
PMID- 29948802
TI - Design and Interpretation of Noninferiority Trials.
PMID- 29948803
TI - Words Matter.
PMID- 29948805
TI - Engagement of Accountable Care Organizations in Acute Care Redesign: Results of a
National Survey.
PMID- 29948804
TI - The Role of Primary Care Experiences in Obtaining Treatment for Depression.
AB - BACKGROUND: Managing depression in primary care settings has increased with the
rise of integrated models of care, such as patient-centered medical homes
(PCMHs). The relationship between patient experience in PCMH settings and receipt
of depression treatment is unknown. OBJECTIVE: In a large sample of Veterans
diagnosed with depression, we examined whether positive PCMH experiences
predicted subsequent initiation or continuation of treatment for depression.
DESIGN AND PARTICIPANTS: We conducted a lagged cross-sectional study of
depression treatment among Veterans with depression diagnoses (n = 27,362) in the
years before (Y1) and after (Y2) they completed the Veterans Health
Administration's national 2013 PCMH Survey of Healthcare Experiences of Patients.
MAIN MEASURES: We assessed patient experiences in four domains, each categorized
as positive/moderate/negative. Depression treatment, determined from
administrative records, was defined annually as 90 days of antidepressant
medications or six psychotherapy visits. Multivariable logistic regressions
measured associations between PCMH experiences and receipt of depression
treatment in Y2, accounting for treatment in Y1. KEY RESULTS: Among those who did
not receive depression treatment in Y1 (n = 4613), positive experiences in three
domains (comprehensiveness, shared decision-making, self-management support)
predicted greater initiation of treatment in Y2. Among those who received
depression treatment in Y1 (n = 22,749), positive or moderate experiences in four
domains (comprehensiveness, care coordination, medication decision-making, self
management support) predicted greater continuation of treatment in Y2.
CONCLUSIONS: In a national PCMH setting, patient experiences with integrated
care, including care coordination, comprehensiveness, involvement in shared
decision-making, and self-management support predicted patients' subsequent
initiation and continuation of depression treatment over time-a relationship that
could affect physical and mental health outcomes.
PMID- 29948806
TI - Incidence of Acute Cardiovascular Event After Acute Exacerbation of COPD.
AB - BACKGROUND: There is a lack of comprehensive view of the association between
acute exacerbation of COPD (AECOPD) and the risk of acute cardiovascular events.
OBJECTIVE: To determine the association of AECOPD with 30-day and 1-year
incidences of acute cardiovascular event. DESIGN: Self-controlled case series
analysis using population-based datasets from three US states from 2005 through
2011. PARTICIPANTS: Patients aged >= 40 years with AECOPD. MAIN MEASURES: The
primary outcome was a composite of an ED visit or hospitalization for acute
cardiovascular events, including acute myocardial infarction, heart failure,
atrial fibrillation, pulmonary embolism, and stroke. We compared the incidence of
each patient's acute cardiovascular event during the first 30-day period before
the index AECOPD (30-day reference period) in comparison with that during the 30
day period after the index AECOPD. Likewise, with the 1-year period before the
index AECOPD as reference, we also estimated incidence rate ratios (IRRs) for
each patient's outcomes during 1-year period after the index AECOPD. KEY RESULTS:
Overall, there were 362,867 patients with an ED visit or hospitalization for
AECOPD. Compared with the 30-day reference period, the incidence of acute
cardiovascular event in the 30-day period after the AECOPD was significantly
higher (IRR, 1.34; 95%CI, 1.30-1.39; P < 0.001). Likewise, compared with the 1
year reference period, the incidence during the 1-year period after the AECOPD
was also higher (IRR, 1.20; 95%CI, 1.18-1.22; P < 0.001). For each of acute
cardiovascular conditions, the associations remained significant (all P < 0.05).
CONCLUSIONS: AECOPD was associated with increased 30-day and 1-year incidences of
acute cardiovascular event.
PMID- 29948807
TI - Implementation of the Chronic Care Model to Reduce Disparities in Hypertension
Control: Benefits Take Time.
AB - BACKGROUND: The Chronic Care Model (CCM) has been endorsed by experts to reduce
disparities in chronic disease outcomes but benefits may be slow to appear in low
income populations. OBJECTIVE: To evaluate the effect of CCM implementation on
systolic blood pressure (SBP) control in minority patients with diabetes mellitus
(DM). DESIGN: Retrospective study from 2012 to 2016 in two primary care clinics
with primarily uninsured, Hispanic patients. PATIENTS: Four 2-year cohorts of
patients aged 18-75 with DM and SBP >= 140 mmHg on HTN drugs in year 1 and SBP
measured 1 year later in year 2. INTERVENTION: Implementation of CCM for DM in
January 2014 involved: electronic medical record revision, a DM registry,
hypertension (HTN) treatment protocol, team education, performance feedback, and
case management. MAIN MEASURE: SBP < 140 mmHg in year 2. KEY RESULTS: Of 2354
patients, the mean age was 56.2 (SD 9.5), baseline SBP 153.8 (SD 14.9) mmHg, and
79.8% Hispanic. Last SBP < 140 mmHg was 58.4% for cohort 1 (2012-2013) and 68.5%
for cohort 4 (2015-2016). Adjusted odds ratios (AORs) for SBP control versus
cohort 1 were 1.35 (95% CI 1.07, 1.69) for cohort 3 (2014-2015) and 2.13 (95% CI
1.60, 2.80) for cohort 4. AORs for SBP control were reduced by 15% per HTN drug
at baseline (P = 0.001), 9% per HTN drug added at last SBP (P = 0.024), and 22%
for multi-dose HTN drugs (P = 0.004). Among patients with persistent elevated SBP
and represented in multiple cohorts, AORs for control were still over 2-fold
higher for cohort 4 versus cohort 1. CONCLUSIONS: After adopting the CCM for
primarily Hispanic patients with DM, SBP control increased significantly despite
treatment with fewer HTN drugs. Yet improvement took 3-4 years, suggesting that
financial rewards for using the CCM to achieve improved clinical outcomes for low
income, minority patients may be delayed.
PMID- 29948808
TI - Identifying Predictors of Emergency Room Utilization in Primary Care.
PMID- 29948809
TI - Transitions of Care for Postoperative Opioid Prescribing in Previously Opioid
Naive Patients in the USA: a Retrospective Review.
AB - BACKGROUND: New persistent opioid use is a common postoperative complication,
with 6% of previously opioid-naive patients continuing to fill opioid
prescriptions 3-6 months after surgery. Despite these risks, it is unknown which
specialties prescribe opioids to these vulnerable patients. OBJECTIVE: To
identify specialties prescribing opioids to surgical patients who develop new
persistent opioid use. DESIGN, SETTING, AND PARTICIPANTS: Using a national
dataset of insurance claims, we identified opioid-naive patients aged 18-64 years
undergoing surgical procedures (2008-2014) who continued filling opioid
prescriptions 3 to 6 months after surgery. We then examined opioid prescriptions
claims during the 12 months after surgery, and identified prescribing physician
specialty using National Provider Identifier codes. MAIN MEASURES: Percentage of
opioid prescriptions provided by each specialty evaluated at 90-day intervals
during the 12 months after surgery. KEY RESULTS: We identified 5276 opioid-naive
patients who developed new persistent opioid use. During the first 3 months after
surgery, surgeons accounted for 69% of opioid prescriptions, primary care
physicians accounted for 13%, Emergency Medicine accounted for 2%, Physical
Medicine & Rehabilitation (PM&R)/Pain Medicine accounted for 1%, and all other
specialties accounted for 15%. In contrast, 9 to 12 months after surgery,
surgeons accounted for only 11% of opioid prescriptions, primary care physicians
accounted for 53%, Emergency Medicine accounted for 5%, PM&R/Pain Medicine
accounted for 6%, and all other specialties provided 25%. CONCLUSIONS: Among
surgical patients who developed new persistent opioid use, surgeons provide the
majority of opioid prescriptions during the first 3 months after surgery. By 9 to
12 months after surgery, however, the majority of opioid prescriptions were
provided by primary care physicians. Enhanced care coordination between surgeons
and primary care physicians could allow earlier identification of patients at
risk for new persistent opioid use to prevent misuse and dependence.
PMID- 29948811
TI - Capsule Commentary on Lin et. al. Empirical Comparison of Publication Bias Tests
in Meta-analysis.
PMID- 29948810
TI - Prevalence and Correlates of Disordered Eating Behaviors Among Young Adults with
Overweight or Obesity.
AB - BACKGROUND: Clinical and community samples indicate that eating disorders (EDs)
and disordered eating behaviors (DEBs) may co-occur among adolescents and young
adults at a weight status classified as overweight or obese. OBJECTIVE: To
determine the prevalence of EDs and DEBs among young adults at a weight status
classified as overweight or obese using a nationally representative sample and to
characterize differences in prevalence by sex, race/ethnicity, sexual
orientation, and socioeconomic status. DESIGN: Cross-sectional nationally
representative data collected from Wave III of the National Longitudinal Study of
Adolescent to Adult Health (Add Health). PARTICIPANTS: Young adults ages 18-24
years old. MAIN MEASURES: ED diagnosis and DEBs (self-reported binge eating or
unhealthy weight control behaviors including vomiting, fasting/skipping meals, or
laxative/diuretic use to lose weight). Covariates: age, sex, race/ethnicity,
sexual orientation, weight status, and education. KEY RESULTS: Of the 14,322
young adults in the sample, 48.6% were at a weight status classified as
overweight or obese. Compared to young adults at a weight status classified as
underweight or normal weight, those at a weight status classified as overweight
or obese reported a higher rate of DEBs (29.3 vs 15.8% in females, 15.4 vs 7.5%
in males). Logistic regression analyses demonstrated that odds of engaging in
DEBs were 2.32 (95% confidence interval 2.05-2.61) times higher for females
compared to males; 1.66 (1.23-2.24) times higher for Asian/Pacific Islander
compared to White; 1.62 (1.16-2.26) times higher for homosexual or bisexual
compared to heterosexual; 1.26 (1.09-1.44) times higher for high school or less
versus more than high school education; and 2.45 (2.16-2.79) times higher for
obesity compared to normal weight, adjusting for all covariates. CONCLUSIONS: The
high prevalence of DEBs particularly in young adults at a weight status
classified as overweight or obese underscores the need for screening, referrals,
and tailored interventions for DEBs in this population.
PMID- 29948812
TI - Industry Payments to Academic Physicians: a Comparison of Reporting to Two
Government Agencies.
PMID- 29948814
TI - Rising Emergency Admission and Readmission Rates-a Retrospective Study of
Demographic and Socio-economic Factors.
PMID- 29948813
TI - Primary Care Clinicians' Views About the Impact of Medicaid Expansion in
Michigan: A Mixed Methods Study.
AB - BACKGROUND: Michigan's approach to Medicaid expansion, the Healthy Michigan Plan
(HMP), emphasizes primary care, prevention, and incentives for patients and
primary care practitioners (PCPs). OBJECTIVE: Assess PCPs' perspectives about the
impact of HMP on their patients and practices. DESIGN: In 2014-2015, we conducted
semi-structured interviews then a statewide survey of PCPs. SETTING: Interviewees
came from varied types of practices in five Michigan regions selected for
racial/ethnic diversity and a mix of rural and urban settings. Surveys were sent
via mail. PARTICIPANTS: Interviewees were physician (n = 16) and non-physician
practitioners (n = 3). All Michigan PCPs caring for >= 12 HMP enrollees were
surveyed (response rate 55.5%, N = 2104). MEASUREMENTS: PCPs' experiences with
HMP patients and recent changes in their practices. RESULTS: Interviews include
examples of the impact of Medicaid expansion on patients and practices. A
majority of surveyed PCPs reported recent increases in new patients (52.3%) and
patients who had not seen a PCP in many years (56.2%). For previously uninsured
patients, PCPs reported positive impact on control of chronic conditions (74.4%),
early detection of serious illness (71.1%), medication adherence (69.1%), health
behaviors (56.5%), emotional well-being (57.0%), and the ability to work, attend
school, or live independently (41.5%). HMP patients reportedly still had more
difficulty than privately insured patients accessing some services. Most PCPs
reported that their practices had, in the past year, hired clinicians (53.2%)
and/or staff (57.5%); 15.4% had colocated mental health care. Few (15.8%)
reported established patients' access to urgent appointments worsened.
LIMITATIONS: PCP reports of patient experiences may not be accurate. Results
reflect the experiences of PCPs with >= 12 Medicaid patients. Differences between
respondents and non-respondents present the possibility for response bias.
CONCLUSIONS: PCPs reported improved patient access to care, medication adherence,
chronic condition management, and detection of serious illness. Established
patients' access did not diminish, perhaps due to reported practice changes.
PMID- 29948815
TI - Potentially Inappropriate Opioid Prescribing, Overdose, and Mortality in
Massachusetts, 2011-2015.
AB - BACKGROUND: Potentially inappropriate prescribing (PIP) may contribute to opioid
overdose. OBJECTIVE: To examine the association between PIP and adverse events.
DESIGN: Cohort study. PARTICIPANTS: Three million seventy-eight thousand thirty
four individuals age >= 18, without disseminated cancer, who received
prescription opioids between 2011 and 2015. MAIN MEASURES: We defined PIP as (a)
morphine equivalent dose >= 100 mg/day in >= 3 months; (b) overlapping opioid and
benzodiazepine prescriptions in >= 3 months; (c) >= 4 opioid prescribers in any
quarter; (d) >= 4 opioid-dispensing pharmacies in any quarter; (e) cash purchase
of prescription opioids on >= 3 occasions; and (f) receipt of opioids in 3
consecutive months without a documented pain diagnosis. We used Cox proportional
hazards models to identify PIP practices associated with non-fatal opioid
overdose, fatal opioid overdose, and all-cause mortality, controlling for
covariates. KEY RESULTS: All six types of PIP were associated with higher
adjusted hazard for all-cause mortality, four of six with non-fatal overdose, and
five of six with fatal overdose. Lacking a documented pain diagnosis was
associated with non-fatal overdose (adjusted hazard ratio [AHR] 2.21, 95%
confidence interval [CI] 2.02-2.41), as was high-dose opioids (AHR 1.68, 95% CI
1.59-1.76). Co-prescription of benzodiazepines was associated with fatal overdose
(AHR 4.23, 95% CI 3.85-4.65). High-dose opioids were associated with all-cause
mortality (AHR 2.18, 95% CI 2.14-2.23), as was lacking a documented pain
diagnosis (AHR 2.05, 95% CI 2.01-2.09). Compared to those who received opioids
without PIP, the hazard for fatal opioid overdose with one, two, three, and >=
four PIP subtypes were 4.24, 7.05, 10.28, and 12.99 (test of linear trend, p <
0.001). CONCLUSIONS: PIP was associated with higher hazard for all-cause
mortality, fatal overdose, and non-fatal overdose. Our study implies the
possibility of creating a risk score incorporating multiple PIP subtypes, which
could be displayed to prescribers in real time.
PMID- 29948816
TI - Cholangitis complicated by infection of a simple hepatic cyst.
AB - An 87-year-old man was admitted to our hospital due to fever and elevated liver
enzymes. Computed tomography (CT) scan revealed bile duct stones with a dilated
biliary system, which confirmed the diagnosis of cholangitis. A 12-cm simple
hepatic cyst was also seen in the right liver, which had been detected on CT scan
5 years before, and did not change in size. Fever did not subside even after
endoscopic biliary drainage and a repeated CT scan showed an enlarged cyst up to
14 cm, suggesting cyst infection. An enlarged hepatic cyst collapsed after
percutaneous transhepatic drainage, along with resolution of fever. Simple
hepatic cysts are common and most of them are asymptomatic. Infection of simple
hepatic cysts is a rare condition and the major entry route is considered as the
biliary tract as communication between the biliary tract and cysts is reportedly
observed in those cases. However, in our case, no communication was seen on
cholangiogram or cystogram on fluoroscopy and bilirubin level of the cyst
aspirate was low. Given the fact that patients with cholangitis are rarely
complicated by hepatic cyst infection, other routes of bacterial entry to simple
hepatic cysts should also be considered.
PMID- 29948817
TI - Pancreatic metastasis of papillary thyroid carcinoma preoperatively diagnosed by
endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report with
review of literatures.
AB - Pancreatic metastatic tumors from thyroid carcinoma are extremely rare. We report
a case of an 80-year-old female with a pancreatic metastatic tumor derived from
papillary thyroid carcinoma which was initially resected 158 months prior to
detection of the metastatic pancreatic tumor. The patient has encountered
cervical lymph-node metastasis on three occasions following the initial
operation. Metastatic pancreatic lesions and cervical lymph nodes were first
detected using 18-fluorodeoxyglucose positron-emission tomography/computed
tomography, and she was preoperatively diagnosed using endoscopic ultrasound
guided fine-needle aspiration biopsy. A coin lesion, 10 mm in size, was detected
in the left lung by chest computed tomography with no abnormal uptake in 18
fluorodeoxyglucose positron-emission tomography/computed tomography. Distal
pancreatectomy and cervical lymph-node dissection were performed. Adjuvant
chemotherapy with weekly paclitaxel was administered because anaplastic
transformation had been detected in one of the cervical lymph nodes. The patient
eventually died from multiple lung metastases 11 months after removing the
metastatic pancreatic lesion. We reported a rare case of a pancreatic metastatic
tumor from thyroid carcinoma, and found that 18-fluorodeoxyglucose positron
emission tomography/computed tomography and endoscopic ultrasound-guided fine
needle aspiration biopsy are useful for preoperatively diagnosing tumors.
PMID- 29948818
TI - Rapidly growing hepatocellular carcinoma recurrence during direct-acting
antiviral treatment for chronic hepatitis C.
AB - We herein report the case of a woman in her 80s with a recurrent hepatocellular
carcinoma (HCC) tumor that rapidly increased in size during direct-acting
antiviral (DAA) treatment. She suffered from HCC at her initial visit to our
department and underwent hepatectomy. Thereafter, she underwent DAA treatment for
chronic hepatitis C; however, her alpha-fetoprotein (AFP) level rapidly
increased, and a liver tumor of > 1 cm in diameter was observed that had not been
seen immediately before DAA treatment. She underwent hepatectomy again and
moderate to poorly differentiated HCC was diagnosed. The patient's AFP level
showed a rapid increase immediately after the start of DAA treatment; however,
the increase ceased after the first month, and the influence from the surrounding
environment of the tumor was considered to be temporary.
PMID- 29948819
TI - Esophagogastric varices were diagnosed in a non-cirrhotic liver case during long
term follow-up after oxaliplatin-based chemotherapy.
AB - Oxaliplatin, a chemotherapeutic agent for colorectal cancer, has been associated
with pathological evidence of sinusoidal endothelial injury in the liver.
However, esophagogastric varices are a poorly recognized outcome of oxaliplatin
based chemotherapy. We report a 78-year-old man, whose past history of colon
cancer was resection and treatment with mFOLFOX6 for 20 weeks, as adjuvant
chemotherapy. After 3.5-year follow-up of the oxaliplatin-based chemotherapy, he
was diagnosed with esophageal varices without liver dysfunction, indicating that
the hepatotoxicity caused by oxaliplatin could be prolonged after its
administration. Patients who have received oxaliplatin-based chemotherapy should
be followed up carefully over the long term.
PMID- 29948820
TI - New Insights in Understanding and Treating Bone Fracture Pain.
AB - PURPOSE OF REVIEW: This paper describes recent advances in understanding the
mechanisms that drive fracture pain and how these findings are helping develop
new therapies to treat fracture pain. RECENT FINDINGS: Immediately following
fracture, mechanosensitive nerve fibers that innervate bone are mechanically
distorted. This results in these nerve fibers rapidly discharging and signaling
the initial sharp fracture pain to the brain. Within minutes to hours, a host of
neurotransmitters, cytokines, and nerve growth factor are released by cells at
the fracture site. These factors stimulate, sensitize, and induce ectopic nerve
sprouting of the sensory and sympathetic nerve fibers which drive the sharp pain
upon movement and the dull aching pain at rest. If rapid and effective healing of
the fracture occurs, these factors return to baseline and the pain subsides, but
if not, these factors can drive chronic bone pain. New mechanism-based therapies
have the potential to fundamentally change the way acute and chronic fracture
pain is managed.
PMID- 29948821
TI - Part I: Development and Physiology of the Temporomandibular Joint.
AB - PURPOSE OF REVIEW: Investigate the developmental physiology of the
temporomandibular joint (TMJ), a unique articulation between the cranium and the
mandible. RECENT FINDINGS: Principal regulatory factors for TMJ and disc
development are Indian hedgehog (IHH) and bone morphogenetic protein (BMP-2). The
mechanism is closely associated with ear morphogenesis. Secondary condylar
cartilage emerges as a subperiosteal blastema on the medial surface of the
posterior mandible. The condylar articular surface is immunoreactive for tenascin
C, so it is a modified fibrous periosteum with an underlying proliferative zone
(cambrium layer) that differentiates into fibrocartilage. The latter cushions
high loads and subsequently produces endochondral bone. The TMJ is a heavily
loaded joint with three cushioning layers of fibrocartilage in the disc, as well
as in subarticular zones in the fossa and mandibular condyle. The periosteal
articular surface produces fibrocartilage to resist heavy loads, and has unique
healing and adaptive properties for maintaining life support functions under
adverse environmental conditions.
PMID- 29948822
TI - Efficacy and Safety of Intravenous Tenecteplase Bolus in Acute Ischemic Stroke:
Results of Two Open-Label, Multicenter Trials.
AB - BACKGROUND: Tenecteplase (TNK-tPA) is a promising third-generation plasminogen
activator, because of its greater fibrin specificity and longer half-life than
alteplase. There is a paucity of studies on intravenous thrombolysis using TNK
tPA in developing countries. The present study has been undertaken to compare the
efficacy and safety of TNK-tPA with alteplase. METHODS: Two studies were
conducted. Study I was an open-label, randomized study in which two doses of TNK
tPA (0.1 and 0.2 mg/kg) were compared. Study II was an open-label study in which
TNK-tPA 0.2 mg/kg bolus was compared with historical controls. The primary
endpoint for study I and study II was an improvement of >= 8 points or a score of
0 on the National Institutes of Health Stroke Scale (NIHSS) [major neurological
improvement (MNI)] at 24 h. Secondary endpoints for both studies were
neurological improvement as assessed using the NIHSS score, modified Rankin Scale
(mRS) score and the Barthel Index (BI) on days 7, 30 and 90. Minimal disability
was defined as an mRS score of 0 or 1 and good functional recovery as a BI score
of 50-90. Safety was assessed by the proportion of patients having symptomatic
intracranial hemorrhage (sICH) within 36 h and asymptomatic intracranial
hemorrhage at 48 h after treatment. RESULTS: In study I, 20 patients received 0.1
mg/kg and 30 received 0.2 mg/kg TNK-tPA. There was no significant difference in
MNI at 24 h between 0.1 and 0.2 mg/kg TNK-tPA doses. The patients given 0.2 mg/kg
TNK-tPA had a significantly better 3-month outcome (minimal disability, p =
0.007). There was no sICH in study I. In study II, 62 patients (one lost to
follow-up) received 0.2 mg/kg TNK-tPA. MNI was noted in ten patients (16.4%), 3
month minimal disability was noted in 37 patients (60.7%), and good functional
recovery was seen in 33 patients (54.1%). sICH occurred in one patient, and four
patients died. Pooled data of patients in study I and study II receiving 0.2
mg/kg TNK-tPA were compared with data from the historical National Institute of
Neurological Disorders and Stroke (NINDS) trial. For comparison, the primary
endpoint of the NINDS trial (improvement on NIHSS of >= 4 points or a score of 0
at 24 h) was taken. The primary endpoint though was not significantly different
(58.2% vs. 47%, p = 0.08), but with TNK-tPA, greater neurological improvement,
minimal disability (70.3 vs. 39%, p < 0.001) and good functional recovery (36.3
vs. 16%, p < 0.001) was noted at 3 months. There was a lower incidence of sICH
(1.1 vs. 6.4%, p = 0.05) and lower 3-month mortality (5.5 vs. 17%, p = 0.01)
noted with TNK-tPA compared with alteplase. CONCLUSIONS: Intravenous TNK-tPA 0.2
mg/kg administered within 3 hours of symptom onset seems to be well tolerated and
effective option in patients with acute ischemic stroke. TRIAL REGISTRATION:
Clinical Trials Registry-India, www.ctri.nic.in ; unique identifiers:
CTRI/2009/091/000251 and CTRI/2015/02/005556.
PMID- 29948823
TI - Pedobacter aquicola sp. nov., isolated from freshwater.
AB - A non-motile, pink-pigmented bacterial strain designated IMCC25679T, was isolated
from freshwater Lake Chungju of Korea. Phylogenetic trees based on 16S rRNA gene
sequences showed that the strain IMCC25679T formed a lineage within the genus
Pedobacter. The strain IMCC25679T was closely related to Pedobacter daechungensis
Dae 13T (96.4% sequence similarity), Pedobacter rivuli HME8457T (95.3%) and
Pedobacter lentus DS-40T (94.3%). The major fatty acids of IMCC- 25679T were iso
C15:0, iso-C16:0 and summed feature 3 (comprising C16:1omega6c and/or
C16:1omega7c). The major respiratory quinone was MK-7. The major polar lipids
were phosphatidylethanolamine (PE), an unidentified sphingolipid (SL), an
unidentified aminolipid (AL) and three unidentified polar lipids (PL). The DNA G
+ C content of IMCC25679T was 32.2 mol%. Based on the evidence presented in this
study, the strain IMCC25679T represents a novel species within the genus
Pedobacter, with the proposed name Pedobacter aquicola, sp. nov. The type strain
is IMCC25679T (= KACC 19486T = NBRC113131T).
PMID- 29948824
TI - Bacillus ferrooxidans sp. nov., an iron(II)-oxidizing bacterium isolated from
paddy soil.
AB - An endospore-forming bacterium, designated YT-3T, was isolated from a paddy soil
in Yingtan, Jiangxi, China. Cells of strain YT-3T were Gram-positive, rod-shaped,
facultative anaerobic, catalase, and oxidase positive. The optimum growth
temperature and pH were 30 degrees C (ranged from 15 to 50 degrees C) and 6.5-7.0
(ranged from 3 to 11), respectively. Analysis of the 16S rRNA gene sequence
showed that strain YT-3T was affiliated to the genus Bacillus and displayed the
highest similarity to that of Bacillus drentensis JCM 21707T (98.3%), followed by
B. ginsengisoli JCM 17335T (97.8%) and B. fumarioli JCM 21708T (97.0%). The
similarity of rpoB gene sequence between strain YT-3T and B. drentensis JCM
21707T, B. ginsengisoli JCM 17335T and B. fumarioli JCM 21708T was 80.4%, 81.5%,
and 82.1%, respectively. The genomic DNA G + C content was 44.9 mol%. The
predominant respiratory quinone was Menaquinone-7, and meso-diaminopimelic acid
was present in the peptidoglycan layer of cell wall. The major fatty acids were
C15:0 anteiso (36.2%), C14:0 iso (19.6%), C15:0 iso (17.4%), and C16:0 iso
(9.8%). The polar lipid profile consisted of diphosphatidylglycerol,
phosphatidylethanolamine, phosphatidylglycerol, phospholipids, and ammoniac
phospholipids. The DNA-DNA hybridization values between isolate YT-3T and B.
drentensis (JCM 21707T), B. ginsengisoli (JCM 17335T), and B. fumarioli (JCM
21708T) were 36.3%, 30.3%, and 25.3%, respectively. On the basis of
physiological, genetic and biochemical data, strain YT-3T represented a novel
species of the genus Bacillus, for which the name Bacillus ferrooxidans sp. nov
was proposed. The type strain is YT-3T (= KCTC 33875T = CCTCC AB 2017049T).
PMID- 29948825
TI - Taxonomic description and draft genome of Pseudomonas sediminis sp. nov.,
isolated from the rhizospheric sediment of Phragmites karka.
AB - The taxonomic position of a Gram-stain-negative, rod-shaped bacterial strain,
designated PI11T, isolated from the rhizospheric sediment of Phragmites karka was
characterized using a polyphasic approach. Strain PI11T could grow optimally at
1.0% NaCl concentration with pH 7.0 at 30 degrees C and was positive for oxidase
and catalase but negative for hydrolysis of starch, casein, and esculin ferric
citrate. Phylogenetic analysis of 16S rRNA gene sequences indicated that the
strain PI11T belonged to the genus Pseudomonas sharing the highest sequence
similarities with Pseudomonas indoloxydans JCM 14246T (99.72%), followed by,
Pseudomonas oleovorans subsp. oleovorans DSM 1045T (99.29%), Pseudomonas
toyotomiensis JCM 15604T (99.15%), Pseudomonas chengduensis DSM 26382T (99.08%),
Pseudomonas oleovorans subsp. lubricantis DSM 21016T (99.08%), and Pseudomonas
alcaliphila JCM 10630T (99.01%). Experimental DNA-DNA relatedness between strain
PI11T and P. indoloxydans JCM 14246T was 49.4%. The draft genome of strain PI11T
consisted of 4,884,839 bp. Average nucleotide identity between the genome of
strain PI11T and other closely related type strains ranged between 77.25-90.74%.
The polar lipid pattern comprised of phosphatidylglycerol,
diphosphatidylglycerol, and phosphatidylcholine. The major (> 10%) cellular fatty
acids were C18:1omega6c/omega7c, C16:1omega6c/omega7c, and C16:0. The DNA G + C
content of strain PI11T was 62.4 mol%. Based on the results of polyphasic
analysis, strain PI11T was delineated from other closely related type strains. It
is proposed that strain PI11T represents represents a novel species of the genus
Pseudomonas, for which the name Pseudomonas sediminis sp. nov. is proposed. The
type strain is PI11T (= KCTC 42576T = DSMZ 100245T).
PMID- 29948826
TI - Proposal of three novel species of soil bacteria, Variovorax ureilyticus,
Variovorax rhizosphaerae, and Variovorax robiniae, in the family Comamonadaceae.
AB - Three novel bacterial strains (UCM-2T, UCM-G28T, and UCM-G35T) were obtained
while isolating soil bacteria for the development of antibiotics. Cells of these
strains were Gram-negative, non-spore forming, motile by means of a single
flagellum, and rod shaped. In all strains, the predominant isoprenoid quinone was
ubiquinone-8 (Q-8). Cells contained C16:0, summed feature 3 (C16:1omega7c and/or
C16:1omega6c), summed feature 8 (C18:1omega7c and/or C18:1omega6c), and C17:0
cyclo as the major fatty acids, and C10:0 3-OH as the major hydroxy fatty acid.
The polar lipid profiles of the three novel strains were dominated by
diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol. The
genomic DNA G + C contents of strains UCM-2T, UCM-G28T, and UCMG35T were 67.5,
65.9, and 66.4 mol%, respectively. Phylogenetic analyses based on 16S rRNA
sequences showed that strain UCM-2T was most closely related to Variovorax soli
NBRC 106424T, whereas strains UCM-G28T and UCM-G35T were most similar to
Variovorax ginsengisoli Gsoil 3165T. Values indicating DNA-DNA hybridization
between the novel isolates and closely related species in the genus Variovorax
were lower than the 70% cut-off point. These phenotypic, chemotaxonomic, and
phylogenetic data indicate that the three isolates should be classified as new
members of the genus Variovorax, for which the names Variovorax ureilyticus sp.
nov., Variovorax rhizosphaerae sp. nov., and Variovorax robiniae sp. nov. are
proposed. The type strains are UCM-2T (= KACC 18899T = NBRC 112306T), UCMG28T (=
KACC 18900T = NBRC 112307T), and UCM-G35T (= KACC 18901T = NBRC 112308T),
respectively.
PMID- 29948827
TI - Temporal and spatial impact of Spartina alterniflora invasion on methanogens
community in Chongming Island, China.
AB - Methane production by methanogens in wetland is recognized as a significant
contributor to global warming. Spartina alterniflora (S. alterniflora), which is
an invasion plant in China's wetland, was reported to have enormous effects on
methane production. But studies on shifts in the methanogen community in response
to S. alterniflora invasion at temporal and spatial scales in the initial
invasion years are rare. Sediments derived from the invasive species S.
alterniflora and the native species Phragmites australis (P. australis) in
pairwise sites and an invasion chronosequence patch (4 years) were analyzed to
investigate the abundance and community structure of methanogens using
quantitative real-time PCR (qPCR) and Denaturing gradient gel electrophoresis
(DGGE) cloning of the methyl-coenzyme M reductase A (mcrA) gene. For the pairwise
sites, the abundance of methanogens in S. alterniflora soils was lower than that
of P. australis soils. For the chronosequence patch, the abundance and diversity
of methanogens was highest in the soil subjected to two years invasion, in which
we detected some rare groups including Methanocellales and Methanococcales. These
results indicated a priming effect at the initial invasion stages of S.
alterniflora for microorganisms in the soil, which was also supported by the
diverse root exudates. The shifts of methanogen communities after S. alterniflora
invasion were due to changes in pH, salinity and sulfate. The results indicate
that root exudates from S. alterniflora have a priming effect on methanogens in
the initial years after invasion, and the predominate methylotrophic groups
(Methanosarcinales) may adapt to the availability of diverse substrates and
reflects the potential for high methane production after invasion by S.
alterniflora.
PMID- 29948828
TI - Phylogenetic comparison of Epstein-Barr virus genomes.
AB - Technologies used for genome analysis and whole genome sequencing are useful for
us to understand genomic characterization and divergence. The Epstein-Barr virus
(EBV) is an oncogenic virus that causes diverse diseases such as Burkitt's
lymphoma (BL), nasopharyngeal carcinoma (NPC), Hodgkin's lymphoma (HL), and
gastric carcinoma (GC). EBV genomes found in these diseases can be classified
either by phases of EBV latency (type-I, -II, and -III latency) or types of EBNA2
sequence difference (type-I EBV, type-II EBV or EBV-1, EBV-2). EBV from EBV
transformed lymphoblastoid cell line (LCL) establishes type-III latency, EBV from
NPC establishes type-II latency, and EBV from GC establishes type-I latency.
However, other important factors play key roles in classifying numerous EBV
strains because EBV genomes are highly diverse and not phylogenetically related
to types of EBV-associated diseases. Herein, we first reviewed previous studies
to describe molecular characteristics of EBV genomes. Then, using comparative and
phylogenetic analyses, we phylogenetically analyzed molecular variations of EBV
genomes and proteins. The review of previous studies and our phylogenetic
analysis showed that EBV genomes and proteins were highly diverse regardless of
types of EBV-associated diseases. Other factors should be considered in
determining EBV taxonomy. This review will be helpful to understand complicated
phylogenetic relationships of EBV genomes.
PMID- 29948829
TI - Halomonas tibetensis sp. nov., isolated from saline lakes on Tibetan Plateau.
AB - Strains pyc13T and ZGT13 were isolated from Lake Pengyan and Lake Zigetang on
Tibetan Plateau, respectively. Both strains were Gram-negative, catalase- and
oxidase-positive, aerobic, rod-shaped, nonmotile, and nonflagellated bacteria.
Phylogenetic analysis based on 16S rRNA gene sequences showed that strains pyc13T
and ZGT13 belong to the genus Halomonas, with Halomonas alkalicola 56-L4-10aEnT
as their closest neighbor, showing 97.4% 16S rRNA gene sequence similarity. The
predominant respiratory quinone of both strains was Q-9, with Q-8 as a minor
component. The major fatty acids of both strains were C18:1omega6c/C18:1omega7c,
C16:1omega6c/C16:1omega7c, C16:0, and C12:0 3OH. The polar lipids of both strains
consisted of phosphatidylethanolamine, phosphatidylglycerol,
diphosphatidylglycerol, glycolipid, phospholipids of unknown structure containing
glucosamine, and unidentified phospholipids. The DNA G + C content of pyc13T and
ZGT13 were 62.6 and 63.4 mol%, respectively. The DNA-DNA hybridization values of
strain pyc13T were 34, 41, 61, 35, and 35% with the reference strains H.
alkalicola 56-L4-10aEnT, H. sediminicola CPS11T, H. mongoliensis Z-7009T, H.
ventosae Al12T, and H. fontilapidosi 5CRT, respectively. Phenotypic, biochemical,
genotypic, and DNA-DNA hybridization data showed that strains pyc13T and ZGT13
represent a new species within the genus Halomonas, for which the name H.
tibetensis sp. nov. is proposed. The type strain is pyc13T (= CGMCC 1.15949T =
KCTC 52660T).
PMID- 29948831
TI - Edoxaban for the treatment of cancer associated venous thromboembolism as an
alternative to low-molecular-weight-heparin.
PMID- 29948830
TI - Interdependence between iron acquisition and biofilm formation in Pseudomonas
aeruginosa.
AB - Bacterial biofilms remain a persistent threat to human healthcare due to their
role in the development of antimicrobial resistance. To combat multi-drug
resistant pathogens, it is crucial to enhance our understanding of not only the
regulation of biofilm formation, but also its contribution to bacterial
virulence. Iron acquisition lies at the crux of these two subjects. In this
review, we discuss the role of iron acquisition in biofilm formation and how
hosts impede this mechanism to defend against pathogens. We also discuss recent
findings that suggest that biofilm formation can also have the reciprocal effect,
influencing siderophore production and iron sequestration.
PMID- 29948832
TI - Risk factors for heart disease in transfusion-dependent thalassemia: serum
ferritin revisited.
AB - Heart disease remains a leading cause of morbidity and mortality in transfusion
dependent thalassemia (TDT), which can be attributed to several factors but
primarily develops in the setting of iron overload. This was a retrospective
cohort study utilizing Webthal(r) patient data from five major centers across
Italy. Patients without heart disease were followed-up for 10 years (2000-2010)
and data were collected for demographics, splenectomy status, serum ferritin and
hemoglobin levels, and comorbidities associated with heart disease. Among 379
patients analyzed (mean age 22.9 +/- 5.1 years, 47.8% men), 44 (cumulative
incidence: 11.6%) developed heart disease during the period of observation.
Splenectomy (p = 0.002) and serum ferritin level (p < 0.001) were the only risk
factors with significant association with heart disease. A serum ferritin
threshold of >= 3000 ng/mL was the best predictor for the development of heart
disease (86.4% sensitivity and 92.8% specificity, AUC: 0.912, 95% CI 0.852-0.971,
p < 0.001). On multivariate analysis, only a serum ferritin level >= 3000 ng/mL
remained significantly and independently associated with increased risk of heart
disease (HR: 44.85, 95% CI 18.85-106.74), with a 5- and 10-year heart disease
free survival of 58 and 39%. The association between iron overload and heart
disease in patients with TDT is confirmed, yet a new serum ferritin level of 3000
ng/mL to flag increased risk is suggested.
PMID- 29948834
TI - In situ simulation in the management of anaphylaxis in a pediatric emergency
department.
AB - Anaphylaxis is a potentially life-threatening, rapid-onset hypersensitive
reaction, usually treated in the emergency department (ED). Failure to recognize
anaphylaxis leads to under-treatment with epinephrine and even when correctly
diagnosed, epinephrine is not always administered. In addition, often patients
who are treated in the ED are not referred for allergy work-up. Simulation is a
tool that increases exposure to events in a safe environment, allowing trainers
to develop skills without harming patients. The main purpose of our study was to
determine whether in situ simulation training increases the frequency of
epinephrine use. The secondary aim was to observe whether simulation modifies the
number of children investigated over the years before and after the setting up of
the simulation training. All patients with anaphylaxis referred to the Pediatric
Emergency Department (PED) of the Anna Meyer Children's Hospital from 2004 to
2010 [pre-simulation (PRE-s) period], and from 2011 to 2016 [post-simulation
(POST-s) period], were retrospectively included in this observational study.
Simulation was carried out using a high-fidelity patient simulator mannequin
(SimBaby, Laerdal Medical, Inc, Stavanger, NY). The diagnosis of anaphylaxis was
based on the EAACI guidelines. The use of epinephrine significantly increased (p
< 0.05) between the PRE-s and POST-s time periods: 2.4% versus 10% patients,
respectively. During the two time periods, we also observed a significant
increase (p = 0.011) in the number of patients who underwent a complete allergy
work-up: 36% versus 51% patients, respectively. According to our results, the in
situ simulation program improved the correct management of anaphylaxis in terms
of prompt use of epinephrine, and it also led to a higher number of patients
being referred to the allergy unit for evaluation.
PMID- 29948835
TI - Guidelines for the management of osteoporosis and fragility fractures.
AB - The purpose of this document, a result of the harmonisation and revision of
Guidelines published separately by the SIMFER, SIOMMMS/SIR, and SIOT
associations, is to provide practical indications based on specific levels of
evidence and various grades of recommendations, drawn from available literature,
for the management of osteoporosis and for the diagnosis, prevention, and
treatment of fragility fractures. These indications were discussed and formally
approved by the delegates of the Italian Scientific Associations involved in the
project (SIE, SIGG, SIMFER, SIMG, SIMI, SIOMMMS, SIR, and SIOT).
PMID- 29948833
TI - Incidence, features, in-hospital outcomes and predictors of in-hospital mortality
associated with toxic megacolon hospitalizations in the United States.
AB - Toxic megacolon (TM) is a potentially fatal condition characterized by non
obstructive colonic dilatation and systemic toxicity. It is most commonly caused
by inflammatory bowel disease (IBD). Limited data for TM are available
demonstrating incidence, in-hospital outcomes and predictors of mortality. We
sought to investigate incidence, characteristics, mortality and predictors of
mortality associated with it. Data were obtained from the Healthcare Cost and
Utilization Project (HCUP)'s Nationwide Inpatient Sample (NIS) database from
January 2010 through December 2014. An analysis was performed on SAS 9.4 (SAS
Institute Inc., Cary, NC). Patients below 18 years were excluded. A mixed-effects
logistic regression model was developed to analyze predictors of mortality. Thus,
8139 (weighted) cases of TM were diagnosed between 2010 and 2014. TM is more
prevalent in women (56.4%) than in men (43.6%), with a mean age of onset at 62.4
years, affecting whites (79.7%) more than non-whites. The most common reason for
hospital admission included IBD (51.6%) followed by septicemia (10.2%) and
intestinal infections (4.1%). Mean length of stay was 9.5 days and overall in
hospital mortality was 7.9%. Other complications included surgical resection of
the large intestine (11.5%) and bowel obstruction (10.9%). Higher age,
neurological disorder, coagulopathy, chronic pulmonary disease, heart failure,
and renal failure were associated with greater risk of in-hospital mortality. TM
is a serious condition with high in-hospital mortality. Management of TM requires
an inter-disciplinary team approach with close monitoring. Patients with positive
predictors in our study require special attention to prevent excessive in
hospital mortality.
PMID- 29948836
TI - Cerebral infarction following cyanoacrylate endoscopic therapy of duodenal
varices in a patient with a patent foramen ovale.
PMID- 29948837
TI - Development of an In Vitro Cardiac Ischemic Model Using Primary Human
Cardiomyocytes.
AB - Developing experimental models to study ischemic heart disease is necessary for
understanding of biological mechanisms to improve the therapeutic approaches for
restoring cardiomyocytes function following injury. The aim of this study was to
develop an in vitro hypoxic/re-oxygenation model of ischemia using primary human
cardiomyocytes (HCM) and define subsequent cytotoxic effects. HCM were cultured
in serum and glucose free medium in hypoxic condition with 1% O2 ranging from 30
min to 12 h. The optimal hypoxic exposure time was determined using Hypoxia
Inducible Factor 1alpha (HIF-1alpha) as the hypoxic marker. Subsequently, the
cells were moved to normoxic condition for 3, 6 and 9 h to replicate the re
oxygenation phase. Optimal period of hypoxic/re-oxygenation was determined based
on 50% mitochondrial injury via 3-(4,5-dimethylthiazol-2-Yl)-2,5
diphenyltetrazolium bromide assay and cytotoxicity via lactate dehydrogenase
(LDH) assay. It was found that the number of cells expressing HIF-1alpha
increased with hypoxic time and 3 h was sufficient to stimulate the expression of
this marker in all the cells. Upon re-oxygenation, mitochondrial activity reduced
significantly whereas the cytotoxicity increased significantly with time. Six
hours of re-oxygenation was optimal to induce reversible cell injury. The injury
became irreversible after 9 h as indicated by > 60% LDH leakage compared to the
control group cultured in normal condition. Under optimized hypoxic reoxygenation
experimental conditions, mesenchymal stem cells formed nanotube with ischemic HCM
and facilitated transfer of mitochondria suggesting the feasibility of using this
as a model system to study molecular mechanisms of myocardial injury and rescue.
PMID- 29948838
TI - Impact of Clinically Relevant Elliptical Deformations on the Damage Patterns of
Sagging and Stretched Leaflets in a Bioprosthetic Heart Valve.
AB - After implantation of a transcatheter bioprosthetic heart valve its original
circular circumference may become distorted, which can lead to changes in leaflet
coaptation and leaflets that are stretched or sagging. This may lead to early
structural deterioration of the valve as seen in some explanted transcatheter
heart valves. Our in vitro study evaluates the effect of leaflet deformations
seen in elliptical configurations on the damage patterns of the leaflets, with
circular valve deformation as the control. Bovine pericardial tissue heart valves
were subjected to accelerated wear testing under both circular (N = 2) and
elliptical (N = 4) configurations. The elliptical configurations were created by
placing the valve inside custom-made elliptical holders, which caused the
leaflets to sag or stretch. The hydrodynamic performance of the valves was
monitored and high resolution images were acquired to evaluate leaflet damage
patterns over time. In the elliptically deformed valves, sagging leaflets
experienced more damage from wear compared to stretched leaflets; the undistorted
leaflets of the circular valves experienced the least leaflet damage. Free-edge
thinning and tearing were the primary modes of damage in the sagging leaflets.
Belly region thinning was seen in the undistorted and stretched leaflets. Leaflet
and fabric tears at the commissures were seen in all valve configurations. Free
edge tearing and commissure tears were the leading cause of valve hydrodynamic
incompetence. Our study shows that mechanical wear affects heart valve
pericardial leaflets differently based on whether they are undistorted,
stretched, or sagging in a valve configuration. Sagging leaflets are more likely
to be subjected to free-edge tear than stretched or undistorted leaflets.
Reducing leaflet stress at the free edge of non-circular valve configurations
should be an important factor to consider in the design and/or deployment of
transcatheter bioprosthetic heart valves to improve their long-term performance.
PMID- 29948839
TI - Amplitude-Integrated Electroencephalography Predicts Outcome in Patients with
Coma After Acute Brain Injury.
AB - Prognostication of coma patients after brain injury is important, yet
challenging. In this study, we evaluated the predictive value of amplitude
integrated electroencephalography (aEEG) for neurological outcomes in coma
patients. From January 2013 to January 2016, 128 coma patients after acute brain
injury were prospectively enrolled and monitored with aEEG. The 6-month
neurological outcome was evaluated using the Cerebral Performance Category Scale.
aEEG monitoring commenced at a median of 7.5 days after coma onset. Continuous
normal voltage predicted a good 6-month neurological outcome with a sensitivity
of 93.6% and specificity of 85.2%. In contrast, continuous extremely low voltage,
burst-suppression, or a flat tracing was correlated with poor 6-month
neurological outcome with a sensitivity of 76.5% and specificity of 100%. In
conclusion, aEEG is a promising predictor of 6-month neurological outcome for
coma patients after acute brain injury.
PMID- 29948840
TI - Clinical Application of Chromosome Microarray Analysis in Han Chinese Children
with Neurodevelopmental Disorders.
AB - Chromosome microarray analysis (CMA) is a cost-effective molecular cytogenetic
technique that has been used as a first-line diagnostic test in
neurodevelopmental disorders in the USA since 2011. The impact of CMA results on
clinical practice in China is not yet well studied, so we aimed to better
evaluate this phenomenon. We analyzed the CMA results from 434 patients in our
clinic, and characterized their molecular diagnoses, clinical features, and
follow-up clinical actions based on these results. The overall diagnostic yield
for our patients was 13.6% (59 out of 434). This gave a detection rate of 14.7%
for developmental delay/intellectual disability (DD/ID, 38/259) and 12% for
autism spectrum disorders (ASDs, 21/175). Thirty-three recurrent (n >= 2)
variants were found, distributed at six chromosomal loci involving known
chromosome syndromes (such as DiGeorge, Williams Beuren, and Angelman/Prader
Willi syndromes). The spectrum of positive copy number variants in our study was
comparable to that reported in Caucasian populations, but with specific
characteristics. Parental origin tests indicated an effect involving a
significant maternal transmission bias to sons. The majority of patients with
positive results (94.9%) had benefits, allowing earlier diagnosis (36/59),
prioritized full clinical management (28/59), medication changes (7/59), a
changed prognosis (30/59), and prenatal genetic counseling (15/59). Our results
provide information on de novo mutations in Chinese children with DD/ID and/or
ASDs. Our data showed that microarray testing provides immediate clinical utility
for patients. It is expected that the personalized medical care of children with
developmental disabilities will lead to improved outcomes in long-term
developmental potential. We advocate using the diagnostic yield of clinically
actionable results to evaluate CMA as it provides information of both clinical
validity and clinical utility.
PMID- 29948842
TI - Anodal Transcranial Direct-Current Stimulation Over the Right Dorsolateral
Prefrontal Cortex Influences Emotional Face Perception.
AB - The dorsolateral prefrontal cortex (DLPFC) is considered to play a crucial role
in many high-level functions, such as cognitive control and emotional regulation.
Many studies have reported that the DLPFC can be activated during the processing
of emotional information in tasks requiring working memory. However, it is still
not clear whether modulating the activity of the DLPFC influences emotional
perception in a detection task. In the present study, using transcranial direct
current stimulation (tDCS), we investigated (1) whether modulating the right
DLPFC influences emotional face processing in a detection task, and (2) whether
the DLPFC plays equal roles in processing positive and negative emotional faces.
The results showed that anodal tDCS over the right DLPFC specifically facilitated
the perception of positive faces, but did not influence the processing of
negative faces. In addition, anodal tDCS over the right primary visual cortex
enhanced performance in the detection task regardless of emotional valence. Our
findings suggest, for the first time, that modulating the right DLPFC influences
emotional face perception, especially faces showing positive emotion.
PMID- 29948841
TI - Regulatory Effect of General Anesthetics on Activity of Potassium Channels.
AB - General anesthesia is an unconscious state induced by anesthetics for surgery.
The molecular targets and cellular mechanisms of general anesthetics in the
mammalian nervous system have been investigated during past decades. In recent
years, K+ channels have been identified as important targets of both volatile and
intravenous anesthetics. This review covers achievements that have been made both
on the regulatory effect of general anesthetics on the activity of K+ channels
and their underlying mechanisms. Advances in research on the modulation of K+
channels by general anesthetics are summarized and categorized according to four
large K+ channel families based on their amino-acid sequence homology. In
addition, research achievements on the roles of K+ channels in general anesthesia
in vivo, especially with regard to studies using mice with K+ channel knockout,
are particularly emphasized.
PMID- 29948843
TI - Predict MiRNA-Disease Association with Collaborative Filtering.
AB - The era of human brain science research is dawning. Researchers utilize the
various multi-disciplinary knowledge to explore the human brain,such as
physiology and bioinformatics. The emerging disease association prediction
technology can speed up the study of diseases, so as to better understanding the
structure and function of human body. There are increasing evidences that miRNA
plays a significant role in nervous system development, adult function,
plasticity, and vulnerability to neurological disease states. In this paper ,we
proposed the novel improved collaborative filtering-based miRNA-disease
association prediction (ICFMDA) approach. Known miRNA-disease associations can be
viewed as a bipartite network between diseases and miRNAs. ICFMDA defined
significance SIG between pairs of diseases or miRNAs to model the preference on
the choices of other entities. The collaborative filtering algorithm is further
improved by incorporating similarity matrices to enable the prediction for new
miRNA or disease without known associations. Potential miRNA-disease associations
are scored with the addition of bidirectional recommendation results with low
computational cost. ICFMDA achieved a 0.9076 AUC of ROC curve in global leave-one
out cross validation, which outperformed the state-of-the-art models. ICFMDA is a
compact and accurate tool for potential miRNA-disease association prediction. We
hope that ICFMDA would be useful in future miRNA and brain researches,and achieve
better understanding of the nervous system in molecular level, cellular level,
cell change process, and thus can support the research of human brain.
PMID- 29948844
TI - PyPNS: Multiscale Simulation of a Peripheral Nerve in Python.
AB - Bioelectronic Medicines that modulate the activity patterns on peripheral nerves
have promise as a new way of treating diverse medical conditions from epilepsy to
rheumatism. Progress in the field builds upon time consuming and expensive
experiments in living organisms. To reduce experimentation load and allow for a
faster, more detailed analysis of peripheral nerve stimulation and recording,
computational models incorporating experimental insights will be of great help.
We present a peripheral nerve simulator that combines biophysical axon models and
numerically solved and idealised extracellular space models in one environment.
We modelled the extracellular space as a three-dimensional resistive continuum
governed by the electro-quasistatic approximation of the Maxwell equations.
Potential distributions were precomputed in finite element models for different
media (homogeneous, nerve in saline, nerve in cuff) and imported into our
simulator. Axons, on the other hand, were modelled more abstractly as one
dimensional chains of compartments. Unmyelinated fibres were based on the Hodgkin
Huxley model; for myelinated fibres, we adapted the model proposed by McIntyre et
al. in 2002 to smaller diameters. To obtain realistic axon shapes, an iterative
algorithm positioned fibres along the nerve with a variable tortuosity fit to
imaged trajectories. We validated our model with data from the stimulated rat
vagus nerve. Simulation results predicted that tortuosity alters recorded signal
shapes and increases stimulation thresholds. The model we developed can easily be
adapted to different nerves, and may be of use for Bioelectronic Medicine
research in the future.
PMID- 29948845
TI - Context aware decision support in neurosurgical oncology based on an efficient
classification of endomicroscopic data.
AB - PURPOSE: Probe-based confocal laser endomicroscopy (pCLE) enables in vivo, in
situ tissue characterisation without changes in the surgical setting and
simplifies the oncological surgical workflow. The potential of this technique in
identifying residual cancer tissue and improving resection rates of brain tumours
has been recently verified in pilot studies. The interpretation of
endomicroscopic information is challenging, particularly for surgeons who do not
themselves routinely review histopathology. Also, the diagnosis can be examiner
dependent, leading to considerable inter-observer variability. Therefore,
automatic tissue characterisation with pCLE would support the surgeon in
establishing diagnosis as well as guide robot-assisted intervention procedures.
METHODS: The aim of this work is to propose a deep learning-based framework for
brain tissue characterisation for context aware diagnosis support in
neurosurgical oncology. An efficient representation of the context information of
pCLE data is presented by exploring state-of-the-art CNN models with different
tuning configurations. A novel video classification framework based on the
combination of convolutional layers with long-range temporal recursion has been
proposed to estimate the probability of each tumour class. The video
classification accuracy is compared for different network architectures and data
representation and video segmentation methods. RESULTS: We demonstrate the
application of the proposed deep learning framework to classify Glioblastoma and
Meningioma brain tumours based on endomicroscopic data. Results show significant
improvement of our proposed image classification framework over state-of-the-art
feature-based methods. The use of video data further improves the classification
performance, achieving accuracy equal to 99.49%. CONCLUSIONS: This work
demonstrates that deep learning can provide an efficient representation of pCLE
data and accurately classify Glioblastoma and Meningioma tumours. The performance
evaluation analysis shows the potential clinical value of the technique.
PMID- 29948846
TI - Peripheral bronchial identification on chest CT using unsupervised machine
learning.
AB - PURPOSE: To automatically identify small- to medium-diameter bronchial segments
distributed throughout the lungs. METHODS: We segment the peripheral pulmonary
vascular tree and construct cross-sectional images perpendicular to the lung
vasculature. The bronchi running with pulmonary arteries appear as concentric
rings, and potential center points that lie within the bronchi are identified by
looking for circles (using the circular Hough transform) and rings (using a novel
variable ring filter). The number of candidate bronchial center points are
further reduced by using agglomerative hierarchical clustering applied to the
points represented with 18 features pertaining to their 3D position, orientation
and appearance of the surrounding cross-sectional image. Resulting clusters
corresponded to bronchial segments. Parameters of the algorithm are varied and
applied to two experimental data sets to find the best values for bronchial
identification. The optimized algorithm was then applied to a further 21 CT
studies obtained using two different CT vendors. RESULTS: The parameters that
result in the most number of true positive bronchial center points with > 95%
precision are a tolerance of 0.15 for the hierarchical clustering algorithm and a
threshold of 75 HU with 10 spokes for the ring filter. Overall, the performance
on all 21 test data sets from CT scans from both vendors demonstrates a mean
number of 563 bronchial points detected per CT study, with a mean precision of
96%. The detected points across this group of test data sets are relatively
uniformly distributed spatially with respect to spherical coordinates with the
origin at the center of the test imaging data sets. CONCLUSION: We have
constructed a robust algorithm for automatic detection of small- to medium
diameter bronchial segments throughout the lungs using a combination of knowledge
based approaches and unsupervised machine learning. It appears robust over two
different CT vendors with similar acquisition parameters.
PMID- 29948847
TI - Correction to: Radiation exposure for intraoperative 3D scans in a hybrid
operating room: how to reduce radiation exposure for the surgical team.
AB - The original version of this article unfortunately contained a mistake. In
abstract, results section should read.
PMID- 29948848
TI - Bayesian Population Pharmacokinetic Modeling of Eltrombopag in Chronic Hepatitis
C Patients.
AB - BACKGROUND AND OBJECTIVES: Eltrombopag is a thrombopoietic growth factor that is
approved for the treatment of thrombocytopenia in chronic hepatitis C virus (HCV)
patients. We aimed to describe eltrombopag population pharmacokinetics in
hepatitis C patients. Bayesian statistical approach will be applied to screen for
patients' characteristics associated with eltrombopag pharmacokinetic parameters.
METHODS: A population pharmacokinetic analysis was conducted using WinBUGS
version 1.4.3. Data from 483 individuals with chronic HCV infection were
analyzed. This analysis is a secondary analysis of two clinical studies (ENABLE1
and ENABLE2) sponsored by GlaxoSmithKline. Several patients' characteristics were
examined as possible covariates of the population pharmacokinetic model. Prior
information from previous studies was incorporated in the bayesian model as prior
distribution to estimate pharmacokinetic parameters. RESULTS: A two-compartment
pharmacokinetic model with first-order absorption with exponential error model
best fit the data. We identified East Asian race and total bilirubin level as
predictors of eltrombopag clearance. Typical value for distributional clearance
was 0.762 L/h (95% Bayesian credible set, 0.703-0.826), for volume of
distribution of the central and peripheral compartments were 12 L (10.9-13.4) and
10.9 L (10.4-11.5), and for absorption lag time was 0.947 h (0.918-0.977).
Assuming an average total bilirubin of 21.7 umol/L, the typical elimination
clearance value for an East Asian patient was 0.14 L/h and for other races was
0.20 L/h. CONCLUSIONS: Eltrombopag pharmacokinetic behavior was described using
population bayesian approach. This model can be applied to optimize eltrombopag
dosing in order to reduce the incidence of thrombocytopenia in HCV-infected
patient receiving interferon-based therapy.
PMID- 29948849
TI - Publisher Correction to: Text Recycling in Scientific Writing.
AB - The correct legends of figures 1, 2, 5, 12, 13 and 14 read.
PMID- 29948850
TI - Hepatitis C in Laos: A 7-Year Retrospective Study on 1765 Patients.
AB - Hepatitis C virus (HCV) is a global health concern, notably in Southeast Asia,
and in Laos the presentation of the HCV-induced liver disease is poorly known.
Our objective was thus to describe a comprehensive HCV infection pattern in order
to guide national health policies. A study on a group of 1765 patients formerly
diagnosed by rapid test in health centres was conducted at the Centre of
Infectiology Lao Christophe Merieux in Vientiane. The demographic information of
patients, their infection status (viral load: VL), liver function
(aminotransferases) and treatments were analysed. Results showed that gender
distribution of infected people was balanced; with median ages of 53.8 for men
and 51.6 years for women (13-86 years). The majority of patients (72%) were
confirmed positive (VL > 50 IU/mL) and 28% of them had high VL (> 6log10). About
23% of patients had level of aminotransferases indicative of liver damage (> 40
IU/mL); but less than 20% of patients received treatment. Patients rarely
received a second sampling or medical imaging. The survey also showed that
cycloferon, pegylated interferon and ribavirin were the drugs prescribed
preferentially by the medical staff, without following any international
recommendations schemes. In conclusion, we recommend that a population screening
policy and better management of patients should be urgently implemented in the
country, respecting official guidelines. However, the cost of biological analysis
and treatment are significant barriers that must be removed. Public health
resolutions should be immediately enforced in the perspective of meeting the WHO
HCV elimination deadline by 2030.
PMID- 29948851
TI - Coenzyme Q10 Influences on the Levels of TNF-alpha and IL-10 and the Ratio of
Bax/Bcl2 in a Menopausal Rat Model Following Lumbar Spinal Cord Injury.
AB - The roles of the immune response and apoptosis as potential mediators of
secondary damage in spinal cord injury (SCI) are being investigated. Research is
also being done to determine the effects of female gonadal steroids, which
decrease during menopause, and antioxidants, such as coenzyme Q10 (CoQ10) on SCI.
We hypothesized that in the absence of female gonadal steroids, which provide
protection following an SCI, CoQ10 could modulate the expression of cytokines,
such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-10, besides
aquaporin-4 (AQP4) water channels in the CNS, which participate in
neuroinflammation, as well as the Bax and Bcl2 proteins that are involved in
apoptosis at the site of injury. The spinal cord was compressed at the level of
the T10 vertebrae and rats were treated by 10 mg/kg/day CoQ10 for 3 weeks after
surgery. The TNF-alpha and IL-10 expressions were studied using an ELISA. Western
blot was used to investigate the Bax/Bcl-2 ratio, AQP4. The level of TNF-alpha
significantly decreased following the administration of CoQ10 compared with the
level of IL-10. When the treatment group was compared with the OVX-SCI group, the
ratio of Bax/Bcl2 significantly decreased in the groups (P < 0.01). Based on our
findings, CoQ10 could be used to compensate for the absence of the
neuroprotection effects provided by female gonadal steroids via reducing the
inappropriate effects of the two main pathways of secondary damage in SCI
apoptosis.
PMID- 29948852
TI - The Mental Health in Austrian Teenagers (MHAT) Study: design, methodology,
description of study population.
AB - Profound epidemiological data on the prevalence of mental health disorders and
respective risk and protective factors is a prerequisite for adequate prevention,
intervention and service planning. Children and adolescents are regarded as high
priority groups for prevention in this field because of the high chronicity and
individual burden of mental health disorders. The Mental Health in Austrian
Teenagers (MHAT)-Study is the first epidemiological study based on a large
representative sample of adolescents (N > 3700) in Austria in order to obtain the
prevalence of a wide range of behavioral problems and psychiatric disorders.
Adolescents are recruited from multiple settings (schools, course providers for
early school leavers and psychiatric clinics) in order to enhance the
representativity of the sample. A "gold-standard" two-stage design (screening
questionnaire and diagnostic interviews) is used to obtain psychiatric diagnoses
that are based on the 5th edition of the Diagnostic and Statistical Manual of
Mental Disorders which was published by the American Psychiatric Association in
2013. This paper aims at presenting the study design and methodology of the MHAT
study, describing the study population as well as discussing relevant strengths
and limitations.
PMID- 29948853
TI - Shitsan Pai: the establishment of the first biophysics department in the world.
PMID- 29948854
TI - Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg-/-
mice.
AB - Recently we have established a new culture condition enabling the derivation of
extended pluripotent stem (EPS) cells, which, compared to conventional
pluripotent stem cells, possess superior developmental potential and germline
competence. However, it remains unclear whether this condition permits derivation
of EPS cells from mouse strains that are refractory or non-permissive to
pluripotent cell establishment. Here, we show that EPS cells can be robustly
generated from non-permissive NOD-scid Il2rg-/- mice through de novo derivation
from blastocysts. Furthermore, these cells can also be efficiently generated by
chemical reprogramming from embryonic NOD-scid Il2rg-/- fibroblasts. NOD-scid
Il2rg-/- EPS cells can be expanded for more than 20 passages with genomic
stability and can be genetically modified through gene targeting. Notably, these
cells contribute to both embryonic and extraembryonic lineages in vivo. More
importantly, they can produce chimeras and integrate into the E13.5 genital
ridge. Our study demonstrates the feasibility of generating EPS cells from
refractory mouse strains, which could potentially be a general strategy for
deriving mouse pluripotent cells. The generation of NOD-scid Il2rg-/- EPS cell
lines permits sophisticated genetic modification in NOD-scid Il2rg-/- mice, which
may greatly advance the optimization of humanized mouse models for biomedical
applications.
PMID- 29948855
TI - Rapid generation of gene-targeted EPS-derived mouse models through tetraploid
complementation.
AB - One major strategy to generate genetically modified mouse models is gene
targeting in mouse embryonic stem (ES) cells, which is used to produce gene
targeted mice for wide applications in biomedicine. However, a major bottleneck
in this approach is that the robustness of germline transmission of gene-targeted
ES cells can be significantly reduced by their genetic and epigenetic instability
after long-term culturing, which impairs the efficiency and robustness of mouse
model generation. Recently, we have established a new type of pluripotent cells
termed extended pluripotent stem (EPS) cells, which have superior developmental
potency and robust germline competence compared to conventional mouse ES cells.
In this study, we demonstrate that mouse EPS cells well maintain developmental
potency and genetic stability after long-term passage. Based on gene targeting in
mouse EPS cells, we established a new approach to directly and rapidly generate
gene-targeted mouse models through tetraploid complementation, which could be
accomplished in approximately 2 months. Importantly, using this approach, we
successfully constructed mouse models in which the human interleukin 3 (IL3) or
interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse
genome. Our study demonstrates the feasibility of using mouse EPS cells to
rapidly generate mouse models by gene targeting, which have great application
potential in biomedical research.
PMID- 29948856
TI - Diet associated with exercise improves baroreflex control of sympathetic nerve
activity in metabolic syndrome and sleep apnea patients.
AB - PURPOSE: We tested the hypothesis that (i) diet associated with exercise would
improve arterial baroreflex (ABR) control in metabolic syndrome (MetS) patients
with and without obstructive sleep apnea (OSA) and (ii) the effects of this
intervention would be more pronounced in patients with OSA. METHODS: Forty-six
MetS patients without (noOSA) and with OSA (apnea-hypopnea index, AHI > 15
events/h) were allocated to no treatment (control, C) or hypocaloric diet (- 500
kcal/day) associated with exercise (40 min, bicycle exercise, 3 times/week) for 4
months (treatment, T), resulting in four groups: noOSA-C (n = 10), OSA-C (n =
12), noOSA-T (n = 13), and OSA-T (n = 11). Muscle sympathetic nerve activity
(MSNA), beat-to-beat BP, and spontaneous arterial baroreflex function of MSNA
(ABRMSNA, gain and time delay) were assessed at study entry and end. RESULTS: No
significant changes occurred in C groups. In contrast, treatment in both patients
with and without OSA led to a significant decrease in weight (P < 0.05) and the
number of MetS factors (P = 0.03). AHI declined only in the OSA-T group (31 +/- 5
to 17 +/- 4 events/h, P < 0.05). Systolic BP decreased in both treatment groups,
and diastolic BP decreased significantly only in the noOSA-T group. Treatment
decreased MSNA in both groups. Compared with baseline, ABRMSNA gain increased in
both OSA-T (13 +/- 1 vs. 24 +/- 2 a.u./mmHg, P = 0.01) and noOSA-T (27 +/- 3 vs.
37 +/- 3 a.u./mmHg, P = 0.03) groups. The time delay of ABRMSNA was reduced only
in the OSA-T group (4.1 +/- 0.2 s vs. 2.8 +/- 0.3 s, P = 0.04). CONCLUSIONS: Diet
associated with exercise improves baroreflex control of sympathetic nerve
activity and MetS components in patients with MetS regardless of OSA.
PMID- 29948857
TI - Obstructive sleep apnea and the effect of CPAP treatment on ischemia-modified
albumin levels: a multi effect size meta-analysis with diagnostic test accuracy.
AB - PURPOSE: A close association of oxidative stress (OS) and ischemia-modified
albumin (IMA) with obstructive sleep apnea (OSA) has been reported in the
literature, but the results on IMA are ambiguous. We conducted a meta-analysis to
evaluate the association of IMA with OSA and the effect of continuous positive
airway pressure (CPAP) therapy on IMA in patients with OSA. METHODS: Relevant
studies were identified by searching PubMed and other databases in addition to
manual searching of cross-references. Using random-effects model, the
standardized mean differences (SMDs), pooled correlation coefficients and summary
of diagnostic test accuracies were obtained with 95% confidence intervals (CIs).
The meta-regression, sub-group and sensitivity analyses were performed to explore
heterogeneity. The presence of publication bias was tested using funnel plot
analysis followed by Begg's and Egger's tests for statistical signidicance.
RESULTS: This meta-analysis finally included nine studies. When comparing with
non-OSA controls, the OSA patients showed a significantly increased circulatory
IMA levels (SMD = 1.15, p = 0.0001). And, this increase is even more pronounced
in severe-OSA group as compared to mild-moderate OSA patients (SMD = 076, p =
0.0006). A decrease in post-CPAP treatment IMA was observed when compared with
that of baseline values. Meta-analysis of correlations showed significant
associations of IMA with polysomnographic parameters. The pooled diagnostic odds
ratio and area under curve were 19.58 and 0.888 (Q* = 0.819), respectively. There
was no evidence of publication bias for the association of IMA with OSA.
CONCLUSION: This meta-analysis suggests that OSA is associated with significantly
increased IMA levels which may indicate OS, ischemia and subclinical
cardiovascular risk. In the diagnostic test accuracy meta-analysis, IMA showed
good accuracy for OSA detection. However, further studies are required to
establish its clinical utility.
PMID- 29948858
TI - Beneficial effects of adaptive servo-ventilation on natriuretic peptides and
diastolic function in acute heart failure patients with preserved ejection
fraction and sleep-disordered breathing.
AB - PURPOSE: Adaptive servo-ventilation (ASV) is a ventilator algorithm able to
correct breathing through anticyclic support of breathing in patients with
central sleep apnea (CSA). So far, very few data exist regarding the role of ASV
on acute heart failure with preserved ejection fraction (HFpEF). METHODS: We
performed a single-center prospective, randomized, case-control study in
consecutive acute HFpEF (left ventricle ejection fraction, LVEF >= 45%) patients
with sleep-disordered breathing (SDB, apnea-hypopnea index, AHI > 15/h) and
prevalence of CSA. RESULTS: We included ten consecutive patients randomized for
ASV on top of standard therapy for acute heart failure (group 1) versus standard
care alone (group 2). ASV therapy significantly reduced AHI and CSA. An
improvement in cardiac diastolic function was seen in group 1 compared to group 2
(E/E' 17.5 to 9.6, p < 0.02 vs 18.5 to 14.5, p = 0.4). Brain natriuretic peptide
(BNP) markedly decreased in cases, but not in controls (298 to 84 pg/ml, p < 0.02
vs 280 to 120 pg/ml, p = 0.06). Right ventricle (RV) function significantly
improved in group 1, differently from group 2. CONCLUSIONS: An acute use of ASV
seems effective in reducing BNP and improving diastolic and RV function in acute
HFpEF patients with SDB and CSA, compared to standard treatment.
PMID- 29948859
TI - More Than Just Keeping Busy: The Protective Effects of Organized Activity
Participation on Violence and Substance Use Among Urban Youth.
AB - Violence and substance use disproportionately affect African American youth in
urban, disadvantaged communities. Expanding positive peer and adult connections
is a mechanism by which organized activity participation may reduce risk of
negative outcomes. We assessed if organized activity participation decreases the
likelihood of later negative outcomes through expanding positive social
connections using a parallel mediation model (Wave 1: N = 681; 50% female; Mage =
14.86 years; SD = 0.65). We found indirect effects from participation to
cigarette use (b = -0.04, 95% CI: -0.07, -0.01) and violent behavior (b = -0.04;
95% CI: -0.07, -0.01) through positive peer connections. We did not find indirect
effects through positive adult connections. This may be because of the notable
influence of peers on negative outcomes during adolescence. Organized activities
can help youth expand positive peer connections, which, in turn, reduces risk of
later negative outcomes. Implications for prevention are discussed.
PMID- 29948861
TI - Adolescents' Self-Perception of Morality, Competence, and Sociability and their
Interplay with Quality of Family, Friend, and School Relationships: A Three-Wave
Longitudinal Study.
AB - Morality, competence, and sociability have been conceptualized as fundamental
dimensions on which individuals ground their evaluation of themselves and of
other people and groups. In this study, we examined the interplay between self
perceived morality, competence, and sociability and relationship quality within
the core social contexts with which adolescents have extensive daily interactions
(family, friends, and school). Participants were 916 (51.4% girls; Mage = 15.64
years) adolescents involved in a three-wave longitudinal study with annual
assessments. The results of cross-lagged analyses indicated that (a) self
perceived morality was more important than self-perceived competence and
sociability in strengthening family, friend, and school relationships; and (b)
high-quality friendships led to increasing levels of self-perceived morality over
time. Overall, this evidence advances our theoretical understanding of the
primacy of morality from a self-perspective approach and highlights the
developmental importance of friends.
PMID- 29948860
TI - Effects of Indirect Exposure to Homicide Events on Children's Mental Health:
Evidence from Urban Settings in Colombia.
AB - Exposure to neighborhood violence is an important risk factor for the social and
emotional development of children and youth. Previous work recognizes that
violence may affect children indirectly via secondhand exposure; yet, few studies
have aimed to identify and quantify these effects, especially in settings like
Colombia where youth is chronically exposed to violence. To address this gap in
the literature, this article implements an empirical strategy where
geographically specific and time-stamped data are leveraged to identify the
effect of indirect exposure to homicides on fifth grade children's social and
emotional outcomes. Sample participants (N = 5801) represent the fifth-grade
population of boys and girls (50.7%) in two major urban areas in the country
(Mage = 11.01, SD = 0.75). We hypothesize that the effects of exposure to
neighborhood violence on children's social and emotional skills will be
consistent and negative. The findings indicate a consistent negative effect of
indirect exposure to homicides on children's emotional functioning (i.e.,
emotional regulation and empathy), as well as on the prevalence of avoidance
behaviors. However, contrary to theoretical expectations, the results do not
support effects on children's levels of aggressive behavior, nor on the beliefs
and attitudes that justify the use of aggression in interpersonal relationships.
The findings are discussed in light of predictions from social cognitive models
and their implications for developmentally and trauma-informed interventions for
youth.
PMID- 29948862
TI - Is sodium thiosulfate an effective treatment for recurrent calcium
nephrolithiasis? Pro and con arguments.
PMID- 29948863
TI - Nephrotoxicity of iodixanol versus iopamidol in patients undergoing peripheral
angiography with or without endovascular therapy.
AB - PURPOSE: To compare the nephrotoxic effects of iodixanol and iopamidol in
patients undergoing peripheral angiography. METHODS: Patients scheduled for
peripheral angiography were randomly assigned to the iodixanol group (n = 463)
and iopamidol group (n = 458). The primary endpoint was the incidence of contrast
associated acute kidney injury (CA-AKI), which was defined as an increase >= 25%
or >= 44.2 umol/l (0.5 mg/dl) in serum creatinine (SCr) from baseline within 72 h
after receiving contrast media (CM). The secondary endpoints were the mean peak
SCr increase within 72 h after receiving CM and major adverse renal events (SCr
increased by two times after 30 days, the need for dialysis treatment,
rehospitalization for acute renal failure, or kidney-related death) during
hospitalization and within 30 day postdischarge. RESULTS: The incidence of CA-AKI
did not differ significantly between the iodixanol group and iopamidol group
(18.1% vs. 16.8%; p = 0.595). There was no significant difference in the mean
peak SCr increase between the iodixanol group and iopamidol group (10.4 +/- 13.0
vs. 10.6 +/- 14.3 umol/l, p = 0.919). There were four patients [1 (0.2%) patient
in the iodixanol group and 1 (0.7%) patients in the iopamidol group, p = 0.609]
with doubling of SCr; no other adverse renal events were observed. CONCLUSIONS:
Our data showed that the nephrotoxicity of iodixanol was comparable with that of
iopamidol in patients undergoing peripheral angiography.
PMID- 29948864
TI - The use of anti-ulcer agents and the risk of chronic kidney disease: a meta
analysis.
AB - PURPOSE: We conducted a meta-analysis to explore the association between the use
of different anti-ulcer agents and the risk of chronic kidney disease (CKD), end
stage renal disease (ESRD), and decline in glomerular filtration rate (GFR) in
various study populations. METHODS: PubMed, Embase, and the Cochrane Library were
searched for relevant entries up to July 1, 2017. The primary outcomes of the
meta-analysis were risk ratios (RRs) of CKD, ESRD, and decline in GFR. We also
investigated the heterogeneity of the meta-analysis by subgroup analysis and meta
regression analysis. RESULTS: A total of 662,624 individuals were enrolled in
five trials. Compared with non-PPI users, PPI users had a higher trend of CKD (RR
= 1.16, 95% CI 1.07-1.25, P < 0.001), especially ESRD (RR = 1.81, 95% CI 1.59
2.06, P < 0.001). There was an elevated risk of adverse renal outcome among
participants receiving PPI and not H2RA (CKD: RR = 1.28, 95% CI 1.24-1.33, P <
0.001; ESRD: RR = 1.39, 95% CI 1.17-1.64, P < 0.001; GFR: RR = 1.31, 95% CI 1.26
1.36, P < 0.001). However, H2RA users were not associated with CKD when compared
with non-H2RA users (RR = 1.02, 95% CI 0.83-1.25, P = 0.855). In subgroup
analysis, the average age of individuals and drug dosage had no influence on the
risk of CKD, while duration of PPI exposure from 31 to 720 days is a potential
factor in progression to ESRD (P < 0.001). CONCLUSIONS: Chronic PPI use, but not
H2RAs, is associated with deterioration in kidney function.
PMID- 29948865
TI - Assessment of creatinine and cystatin C-based eGFR equations in Chinese older
adults with chronic kidney disease.
AB - INTRODUCTION: Glomerular filtration rate (GFR) estimation equations using
creatinine and Cystatin-C appear to be superior to those based on creatinine or
Cystatin-C in older adults. We sought to compare the performances of those based
on creatinine and Cystatin-C in Chinese older adults with chronic kidney disease
(CKD). METHODS: A total of 368 Chinese elderly with CKD underwent the dynamic
imaging with technetium-99m diethylene-triamine-pentaacetic acid (99mTc-DTPA),
and serum creatinine and Cystatin-C were measured on the same day. The comparison
of GFR equations which were creatinine and Cystatin-C-based including chronic
kidney disease epidemiology collaboration (CKD-EPI) equation (CKD-EPI-Cr-Cys),
Berlin Initiative Study (BIS) equation (BIS-Cr-Cys, also known as BIS-2), MA
equation (MA-Cr-Cys), and FENG equation (FENG-Cr-Cys) was conducted. RESULTS:
Four equations overestimated GFR except for BIS-2 equation in mGFR >= 60
ml/min/1.73 m2 (bias: - 1.40, p = 0.7) and CKD-EPI-Cr-Cys equation in mGFR < 30
ml/min/1.73 m2 (bias: - 1.82, p = 0.2) were unbiased. BIS-2 equation had the
smallest interquartile range (IQR, ml/min/1.73 m2) from 12.73 in age < 75 years
group to 16.05 in age >= 75 years group. BIS-2 equation achieved highest values
of 79.1% in overall participants, and 80.77% in age >= 75 years group,
respectively, and CKD-EPI-Cr-Cys equation 82.26% in age < 75 years group. Lowest
values of root-mean-square error (RMSE, ml/min/1.73 m2) were seen in BIS-2
equation from 13.22 in age < 75 years group to 16.18 in age >= 75 years group.
BIS-2 equation had the lowest misclassification rates of 41.76% in age >= 75
years group and 34.41% in age < 75 years group. CONCLUSIONS: BIS-2 equation may
be optimal for Chinese older adults with CKD especially in older adults >= 75
years and with mGFR >= 30 ml/min/1.73 m2, while CKD-EPI-Cr-Cys equation could
yield a better performance than BIS-2 equation, especially in those < 75 years
and mGFR < 30 ml/min/1.73 m2.
PMID- 29948866
TI - Sentinel lymph node dissection in prostate cancer using superparamagnetic
particles of iron oxide: early clinical experience.
AB - PURPOSE: Superparamagnetic nanoparticles of iron oxide (SPION) were shown to be
non-inferior to standard radioisotope tracer in breast cancer and may be used as
an alternative to identify sentinel lymph nodes (SLN). The aim of this study was
to assess the feasibility of sentinel lymph node dissection (SLND) using SPION in
prostate cancer and to evaluate its diagnostic accuracy. METHODS: Twenty patients
with intermediate- and high-risk prostate cancer were prospectively enrolled in
2016. After intraprostatic injection of SPION, SLND using magnetometer was
performed the following day. Extended pelvic lymph node dissection (ePLND) was
added as a reference standard test. The diagnostic performance of the test were
evaluated, as well as the rate of in vivo detected SLN. Surgical times of SLND
and ePLND were compared using paired two-sample t test. RESULTS: In total, 97 SLN
were detected with median 5 (IQR 3-7) per patient. Non-diagnostic rate of the
procedure was 5%. In total, 19 nodal metastases were found in 5 patients, of
which 12 were located in SLN. The sensitivity per patient for the whole cohort
was 80% and per node 56%. If only patients with at least one detected SLN were
considered, the sensitivity per patient and per node reached 100 and 82%,
respectively. A median of 20 LNs (IQR 18-22) were removed by subsequent ePLND.
Surgical times of SLND and ePLND differed significantly, with medians of 17 and
39 min, respectively (p < 0.001). CONCLUSIONS: SLND with SPION is feasible and
safe in prostate cancer and the diagnostic accuracy is comparable to the
published results of radioguided procedures. In open surgery, SPION may be used
as an alternative tracer with its main advantage being the lack of radiation
hazard.
PMID- 29948867
TI - Long term outcomes in the use of ileal ureter for radiation-induced ureteral
strictures.
AB - PURPOSE: Radiation-induced ureteral stricture disease poses significant surgical
challenges. Ureteral substitution with ileum has long been a versatile option for
reconstruction. We evaluated outcomes in patients undergoing ileal ureter
replacement for ureteral reconstruction due to radiation-induced ureteral
stricture versus other causes. METHODS: Between July 1989 and June 2013, 155
patients underwent consecutive ileal ureter creation. The study cohort included
104 patients with complete data sets and at least 7 months of follow up. Records
were retrospectively reviewed with regard to demographics, indications,
complications, and renal deterioration. RESULTS: Surgical indications included
radiation-induced stricture in 23 (22%) and non-radiation-induced stricture in 81
(78%). Comparing ileal ureter substitution due to radiation versus other
stricture etiologies, no statistical significance was observed in regard to age
(45.6 vs. 51.2, p = 0.141), hospital length of stay in days (8.8 vs. 7.7, p =
0.216), percent GFR loss (MDRD-4 vs. -5%, p = 0.670 and CKD-EPI-7 vs. -6%, p =
0.914), 30-day surgical complications (26.1 vs. 30.1%, p = 0.658), metabolic
acidosis (8.7 vs. 1.2%, p = 0.059), and renal failure requiring dialysis (4.3 vs.
1.2%, p = 0.337). Fistula formation (13.0 vs. 3.7%, p = 0.095), partial small
bowel obstructions (21.7 vs. 7.4%, p = 0.063), and small bowel obstructions
requiring reoperation (13.0 vs. 1.2%, p = 0.033) approached or reached
statistical significance. Using Kaplan-Meier methodology, there was no difference
in time to worsening renal outcome between the radiation and non-radiation groups
(p > 0.05). CONCLUSION: Ureteral substitution with ileum is an effective
reconstructive option for radiation-induced ureteral strictures in carefully
selected patients.
PMID- 29948869
TI - A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Acetaminophen
on Hospital Length of Stay in Obese Individuals Undergoing Sleeve Gastrectomy.
AB - BACKGROUND: Retrospective studies indicate that acetaminophen iv administration
reduces hospital length of stay (LoS) and opiate consumption in patients
undergoing bariatric surgery. OBJECTIVE: This study sought to determine whether
using acetaminophen iv in morbidly obese subjects undergoing sleeve gastrectomy
decreased LoS and total hospital charges as compared to patients receiving saline
placebo. SETTING: Single-center university hospital METHODS: Using a randomized,
double-blind, placebo-controlled design, subjects were assigned to receive either
acetaminophen iv (group A) or saline placebo iv (group P). Data were collected
between Jan 1 and Dec 31, 2016. Group A received acetaminophen every 6 h for a
total of four doses. The first dose was administered following the induction of
general anesthesia; group P received saline iv on the same schedule. Anesthetic
management and prophylactic antiemetic regimen were standardized in all subjects.
Postoperative pain management consisted of hydromorphone via patient-controlled
infusion pump. Primary outcomes include hospital LoS and associated hospital
costs. Secondary outcomes include patient satisfaction and postoperative nausea
and pain scores. RESULTS: Subject demographics (n = 127) and intraoperative
management were similar in the two groups. Across all subjects, median hospital
LoS in group A (n = 63) was 1.87 vs. 1.97 days in group P (n = 64) (p = 0.03,
Wilcoxon rank-sum test). Postoperatively, daily quality-of-recovery (QoR-15)
scores, narcotic consumption, and the use of rescue antiemetics were not
significantly different between groups. Median hospital costs were as follows:
group A, $12,885 vs. group P, $12,977 (n = 64). CONCLUSIONS: Acetaminophen iv may
reduce hospital LoS in subjects undergoing sleeve gastrectomy.
PMID- 29948870
TI - Endobarrier as a Pre Bariatric Surgical Intervention in High-Risk Patients: a
Feasibility Study.
AB - BACKGROUND: Obesity surgery mortality risk scoring system (OS-MRS) classifies
patients into high, intermediate and low risk, based on age, body mass index, sex
and other comorbidities such as hypertension and history of pulmonary embolism.
High-risk patients not only have a higher mortality but are more likely to
develop post-operative complications necessitating intervention or prolonged
hospital stay following bariatric surgery. Endoscopically placed duodenal-jejunal
bypass sleeve (Endobarrier) has been designed to achieve weight loss and improve
glycaemic control in morbidly obese patients with clinically proven
effectiveness. The aim of this study was to assess if pre-operative insertion of
endobarrier in high-risk patients can decrease morbidity and length of stay after
bariatric surgery. MATERIALS AND METHODS: Between 2012 and 2014, a cohort of 11
high-risk patients had an Endobarrier inserted (E&BS group) for 1 year prior to
definitive bariatric surgery. These patients were compared against a similar
group undergoing primary bariatric surgery (PBS group) during same duration. The
two groups were matched for age, gender, body mass index, comorbidities, surgical
procedure and OS-MRS using propensity score matching. Outcome measures included
operative time, morbidity, length of stay, intensive therapy unit (ITU) stay,
readmission rate, percentage excess weight loss (%EWL) and percentage total
weight loss (%TWL). RESULTS: Patient characteristics and OS-MRS were similar in
both groups (match tolerance 0.1). There was no significant difference in total
length of stay, readmission rate, %EWL and %TWL. Operative time, ITU stay, post
operative complications and severity of complications were significantly less in
the E&BS group (p < 0.05) with significant likelihood of planned ITU admissions
in the PBS group (p < 0.05). CONCLUSION: Endobarrier could be considered as a pre
bariatric surgical intervention in high-risk patients. It may result in improved
post-operative outcomes in high-risk bariatric patients.
PMID- 29948868
TI - The potential of non-myeloablative heterochronous autologous hematopoietic stem
cell transplantation for extending a healthy life span.
AB - Aging is a complex multifactorial process, a prominent component being the
senescence of the immune system. Consequently, immune-related diseases develop,
including atherosclerosis, cancer, and life-threatening infections, which impact
on health and longevity. Rejuvenating the aged immune system could mitigate these
diseases, thereby contributing to longevity and health. Currently, an appealing
option for rejuvenating the immune system is heterochronous autologous
hematopoietic stem cell transplantation (haHSCT), where healthy autologous bone
marrow/peripheral blood stem cells are collected during the youth of an
individual, cryopreserved, and re-infused when he or she has reached an older
age. After infusion, young hematopoietic stem cells can reconstitute the
compromised immune system and improve immune function. Several studies using
animal models have achieved substantial extension of the life span of animals
treated with haHSCT. Therefore, haHSCT could be regarded as a potential procedure
for preventing age-related immune defects and extending healthy longevity. In
this review, the pros, cons, and future feasibility of this approach are
discussed.
PMID- 29948872
TI - Comments on "Challenges in Transition of Care for Pediatric Patients after Weight
Reduction Surgery: a Systematic Review and Recommendations for Comprehensive
Care".
PMID- 29948873
TI - Letter to the Editor: MGB and OAGB.
PMID- 29948874
TI - The Effect of Bariatric Surgery on Patients with HIV Infection: a Literature
Review.
AB - Obesity among human immunodeficiency virus (HIV)-infected individuals is on the
rise. Bariatric procedures such as Roux-en-Y gastric bypass (RYGB) and sleeve
gastrectomy (SG) alter the GI tract. Whether this alteration has any impact on
the absorption of highly active antiretroviral therapy (HAART), thus affecting
HIV disease markers such as CD4 cell count or viral load (VL), is not yet known.
We conducted this review to look into the outcomes of bariatric surgery
procedures, RYGB, SG and adjustable gastric band (AGB) and its effects on the CD4
cell counts and VL and HAART therapy. A literature search was conducted between
January and April 2017, by two independent reviewers, using Pubmed and Google
Scholar. The terms 'bariatric surgery and HIV', 'obesity surgery and HIV',
'gastric bypass surgery and HIV', 'sleeve gastrectomy and HIV' and 'gastric band
and HIV' were used to retrieve available research. Of the 49 papers reviewed,
only 12 reported the outcomes of patients with HIV undergoing bariatric surgery
and were therefore included in this review. Six papers assessed patients
undergoing RYGB only (N = 18), 3 papers reported on SG only (N = 18) and 3 papers
reported on case mix, including 7 cases of RYGB, 4 cases of SG and 11 cases of
AGB. Data is limited; however, based on the available data, bariatric surgery is
safe in HIV-infected individuals and does not have any adverse impact on HIV
disease progress. Additionally, there was no difference in HIV-related outcomes
between SG and RYGB.
PMID- 29948875
TI - Open versus robot-assisted radical cystectomy: 30-day perioperative comparison
and predictors for cost-to-patient, complication, and readmission.
AB - The objectives of this study are to evaluate if robotic cystectomy demonstrates
reduced complications, readmissions, and cost-to-patient compared to open
approach 30-day post-operatively, and to identify predictors of complication,
readmission, and cost-to-patient. This retrospective cohort study analyzed 249
patients who underwent open (n = 149) or robotic (n = 100) cystectomy from 2009
to 2015 at our institution. Outcomes included 30-day post-operative complication,
readmission, and cost-to-patient charges. We used modified Clavien-Dindo/MSKCC
classifications. Multivariable logistic and linear regression models were used to
evaluate associations to outcomes and to build predictive models. Patient,
clinical, and surgical characteristics differed by open and robotic groups,
respectively, only for estimated blood loss (median: 600 versus 150 cc, p <
0.01), operative time (mean: 6.19 versus 6.85 h, p < 0.01), and length of stay
(median: 7 versus 5 days, p < 0.01). Complication: frequency of patients with at
least one 30-day complication was 85% compared to 66% (p < 0.01). Minor
gastrointestinal and bleeding complications were increased in the open group (50%
versus 41%, p = 0.01; 52% versus 11%, p < 0.01, respectively). Fifty percent of
patients required blood transfusion in open compared to 11% (p < 0.01). Patients
in the open group experienced more major complications (19% versus 10%, p =
0.04). Robotic approach was a predictor for fewer complications (OR 0.44, 95% CI
0.20-0.99, p = 0.049). Readmission: no significant difference in number of
patients readmitted was found. Cost-to-patient: Robotic approach predicted an 18%
reduction in total cost-to-patient compared to open approach (p < 0.01). Robotic
cystectomy demonstrated reduced total cost-to-patient when taking into account
all 30-day post-operative services with fewer complications compared to open
cystectomy.
PMID- 29948871
TI - Understanding Pathophysiological Concepts Leading to Obstructive Apnea.
AB - Obstructive sleep apnea (OSA) results from a combination of several factors
leading to the obstruction of the upper respiratory tract (URT). OSA represents a
systemic pathophysiological entity and leads to many comorbidities such as
hypertension, coronary ischemia, and stroke. Patients with this
pathophysiological entity experience also an increased risk of postoperative
complications. Obesity is certainly the main cause of developing OSA. However,
many other predisposing factors influence the genesis of obstructive apnea. It is
important to understand the complexity of the interactions between predisposing
factors to understand the relationship between weight loss following obesity
surgery and the improvement in the severity of OSA. In this narrative review, we
expose the seven major categories of predisposing factors that interact to
generate obstructive apneas in patients, namely the anatomic abnormalities of the
URT, the mechanical and the metabolic responses of the upper airway musculature,
the loop gain, the arousal threshold, and the hormonal abnormalities. The genesis
of apnea is the result of a complex dynamic interaction between the anatomical
risk factors and the compensatory neuromuscular reflexes. All of these points are
integrally part of the perioperative care of the obese patients. Finally, we will
discuss different options for weight reduction.
PMID- 29948876
TI - Robotic-assisted, spleen-preserving distal pancreatectomy for a solid
pseudopapillary tumour in a pediatric patient: a case report and review of the
literature.
AB - Solid pseudopapillary tumour is a rare carcinoma of the pancreas with low-grade
malignant potential that typically presents in females in their third decade. The
tumour most commonly occurs in the tail of the pancreas, although any site can be
affected. Surgical resection is the standard treatment and offers an excellent
prognosis. Robotic-assisted laparoscopic surgery is an emerging technique for the
treatment of pancreatic neoplasms. We report a case of a 17-year-old female with
acute onset abdominal pain who was found to have a mass in the distal pancreas. A
robotic-assisted laparoscopic distal pancreatectomy with spleen preservation was
successfully performed, its first reported use in a pediatric patient. The
patient had an uncomplicated recovery. The robotic approach can be considered for
younger patients presenting with a solid pseudopapillary tumour in the distal
pancreas.
PMID- 29948877
TI - Re: Robot-assisted laparoscopic radical prostatectomy: assistant's seniority has
no influence on perioperative course.
PMID- 29948878
TI - Anesthesia experience of pediatric robotic surgery in a University Hospital.
AB - Robotic technology has a promising future in surgical field. Robotic-assisted
laparoscopy is a newly advance technology which is highly accepted by most of
surgeons in various surgical procedures. As the pediatric surgeons adopt and
master robotic technique, anesthesiologists familiarized themselves with this
technique as well. Robotic surgery required a high-quality of perioperative
anesthesia care that is essential for optimizing surgical outcome and patient
safety. A retrospective analysis of robotic-assisted surgery for all children
under age of 18 years from June 2004 to November 2013 at King Khalid University
Hospital was conducted. Data of demographic (age, sex, and weight), type of
procedures, operative time, intraoperative and postoperative complications were
noted. Seventy robot assisted laparoscopy procedures were performed using the da
Vinci surgical system. All procedures except three cases were successfully
completed using robot with mean operative time of 110 min. Nissen fundoplication
(34 cases) was the commonest robotic surgical procedure performed followed by
cholecystectomy, anal-pull through and gastric banding. There were no
intraoperative and postoperative complications related to anesthesia. Robotic
assisted laparoscopy is a safe and feasible technique for a variety of pediatric
procedures. Our findings suggest that, perioperative anesthesia care should be
considered in advance with high anesthetic precautions to maximize patient safety
and improve surgical outcome. It is worth to have more studies measuring clinical
anesthesia outcome of pediatric robotic surgery.
PMID- 29948879
TI - Zoledronate increases enrichment, activation and expansion of natural killer
cells from umbilical cord blood.
PMID- 29948880
TI - Grid-like units help deep learning agent to navigate.
AB - An artificial-intelligence model based on deep learning developed units in a
hidden layer that resembled mammalian grid cells in the hippocampus when the
agent was taught to integrate paths. The full model performed sophisticated
navigational tasks-in some cases even better than a human.
PMID- 29948881
TI - Transmission Dynamics of an SIS Model with Age Structure on Heterogeneous
Networks.
AB - Infection age is often an important factor in epidemic dynamics. In order to
realistically analyze the spreading mechanism and dynamical behavior of epidemic
diseases, in this paper, a generalized disease transmission model of SIS type
with age-dependent infection and birth and death on a heterogeneous network is
discussed. The model allows the infection and recovery rates to vary and depend
on the age of infection, the time since an individual becomes infected. We
address uniform persistence and find that the model has the sharp threshold
property, that is, for the basic reproduction number less than one, the disease
free equilibrium is globally asymptotically stable, while for the basic
reproduction number is above one, a Lyapunov functional is used to show that the
endemic equilibrium is globally stable. Finally, some numerical simulations are
carried out to illustrate and complement the main results. The disease dynamics
rely not only on the network structure, but also on an age-dependent factor (for
some key functions concerned in the model).
PMID- 29948882
TI - Cover-Encodings of Fitness Landscapes.
AB - The traditional way of tackling discrete optimization problems is by using local
search on suitably defined cost or fitness landscapes. Such approaches are
however limited by the slowing down that occurs when the local minima that are a
feature of the typically rugged landscapes encountered arrest the progress of the
search process. Another way of tackling optimization problems is by the use of
heuristic approximations to estimate a global cost minimum. Here, we present a
combination of these two approaches by using cover-encoding maps which map
processes from a larger search space to subsets of the original search space. The
key idea is to construct cover-encoding maps with the help of suitable heuristics
that single out near-optimal solutions and result in landscapes on the larger
search space that no longer exhibit trapping local minima. We present cover
encoding maps for the problems of the traveling salesman, number partitioning,
maximum matching and maximum clique; the practical feasibility of our method is
demonstrated by simulations of adaptive walks on the corresponding encoded
landscapes which find the global minima for these problems.
PMID- 29948883
TI - Structural and Practical Identifiability Analysis of Zika Epidemiological Models.
AB - The Zika virus (ZIKV) epidemic has caused an ongoing threat to global health
security and spurred new investigations of the virus. Use of epidemiological
models for arbovirus diseases can be a powerful tool to assist in prevention and
control of the emerging disease. In this article, we introduce six models of
ZIKV, beginning with a general vector-borne model and gradually including
different transmission routes of ZIKV. These epidemiological models use various
combinations of disease transmission (vector and direct) and infectious classes
(asymptomatic and pregnant), with addition to loss of immunity being included.
The disease-induced death rate is omitted from the models. We test the structural
and practical identifiability of the models to find whether unknown model
parameters can uniquely be determined. The models were fit to obtain time-series
data of cumulative incidences and pregnant infections from the Florida Department
of Health Daily Zika Update Reports. The average relative estimation errors
(AREs) were computed from the Monte Carlo simulations to further analyze the
identifiability of the models. We show that direct transmission rates are not
practically identifiable; however, fixed recovery rates improve identifiability
overall. We found ARE is low for each model (only slightly higher for those that
account for a pregnant class) and help to confirm a reproduction number greater
than one at the start of the Florida epidemic. Basic reproduction number,
[Formula: see text], is an epidemiologically important threshold value which
gives the number of secondary cases generated by one infected individual in a
totally susceptible population in duration of infectiousness. Elasticity of the
reproduction numbers suggests that the mosquito-to-human ratio, mosquito life
span and biting rate have the greatest potential for reducing the reproduction
number of Zika, and therefore, corresponding control measures need to be focused
on.
PMID- 29948884
TI - Evaluation and Calibration of In Silico Models of Thrombin Generation Using
Experimental Data from Healthy and Haemophilic Subjects.
AB - The coagulation cascade comprises numerous chemical reactions between many
proteins, that finally lead to the formation of a clot to stop bleeding. Many
numerical models have attempted to translate understanding of this cascade into
mathematical equations that simulate the chain reactions. However, their
predictions have not been validated against clinical data stemming from patients.
In this paper, we propose an extensive validation of five available models, by
comparing in healthy and haemophilic subjects, thrombin generation measured in
vitro to thrombin generation predicted by the models in silico. In order to
render the models more predictive, we calibrated the models to have an acceptable
agreement between the experimental and estimated data. Optimization processes
based on genetic algorithms were developed to search for those calibrated kinetic
parameters. Our results show that the thrombin generation kinetics are so complex
that they cannot be predicted by a unique set of kinetic parameters for all
patients: the calibration of only three parameters in a subject-specific way
allows reaching good model estimations for different experimental conditions
realized on the same patient.
PMID- 29948885
TI - Exploring the Tiers of Rooted Phylogenetic Network Space Using Tail Moves.
AB - Popular methods for exploring the space of rooted phylogenetic trees use
rearrangement moves such as rooted Nearest Neighbour Interchange (rNNI) and
rooted Subtree Prune and Regraft (rSPR). Recently, these moves were generalized
to rooted phylogenetic networks, which are a more suitable representation of
reticulate evolutionary histories, and it was shown that any two rooted
phylogenetic networks of the same complexity are connected by a sequence of
either rSPR or rNNI moves. Here, we show that this is possible using only tail
moves, which are a restricted version of rSPR moves on networks that are more
closely related to rSPR moves on trees. The connectedness still holds even when
we restrict to distance-1 tail moves (a localized version of tail moves).
Moreover, we give bounds on the number of (distance-1) tail moves necessary to
turn one network into another, which in turn yield new bounds for rSPR, rNNI and
SPR (i.e. the equivalent of rSPR on unrooted networks). The upper bounds are
constructive, meaning that we can actually find a sequence with at most this
length for any pair of networks. Finally, we show that finding a shortest
sequence of tail or rSPR moves is NP-hard.
PMID- 29948886
TI - Predictive Modeling of Neuroblastoma Growth Dynamics in Xenograft Model After
Bevacizumab Anti-VEGF Therapy.
AB - Neuroblastoma is the leading cause of cancer death in young children. Although
treatment for neuroblastoma has improved, the 5-year survival rate of patients
still remains less than half. Recent studies have indicated that bevacizumab, an
anti-VEGF drug used in treatment of several other cancer types, may be effective
for treating neuroblastoma as well. However, its effect on neuroblastoma has not
been well characterized. While traditional experiments are costly and time
consuming, mathematical models are capable of simulating complex systems quickly
and inexpensively. In this study, we present a model of vascular tumor growth of
neuroblastoma IMR-32 that is complex enough to replicate experimental data across
a range of tumor cell properties measured in a suite of in vitro and in vivo
experiments. The model provides quantitative insight into tumor vasculature,
predicting a linear relationship between vasculature and tumor volume. The tumor
growth model was coupled with known pharmacokinetics and pharmacodynamics of the
VEGF blocker bevacizumab to study its effect on neuroblastoma growth dynamics.
The results of our model suggest that total administered bevacizumab
concentration per week, as opposed to dosage regimen, is the major determining
factor in tumor suppression. Our model also establishes an exponentially
decreasing relationship between administered bevacizumab concentration and tumor
growth rate.
PMID- 29948887
TI - Steroid Hormone Reactivity in Fathers Watching Their Children Compete.
AB - This study examines steroid production in fathers watching their children
compete, extending previous research of vicarious success or failure on men's
hormone levels. Salivary testosterone and cortisol levels were measured in 18
fathers watching their children play in a soccer tournament. Participants
completed a survey about the game and provided demographic information. Fathers
with higher pregame testosterone levels were more likely to report that referees
were biased against their children's teams, and pre- to postgame testosterone
elevation was predicted by watching sons compete rather than daughters as well as
perceptions of unfair officiating. Pregame cortisol was not associated with
pregame testosterone or with perceived officiating bias, but cortisol did
fluctuate synergistically with testosterone during spectator competition.
Although fathers showed no consistent testosterone change in response to winning
or losing, pregame testosterone may mediate steroid hormone reactivity to other
aspects of their children's competition.
PMID- 29948888
TI - Ammonia for exercise positron emission tomography (PET): A promising technique
for patients with LBBB and suspicion of coronary artery disease. A case study.
PMID- 29948889
TI - Optimization of reconstruction and quantification of motion-corrected coronary
PET-CT.
AB - BACKGROUND: Coronary PET shows promise in the detection of high-risk
atherosclerosis, but there remains a need to optimize imaging and reconstruction
techniques. We investigated the impact of reconstruction parameters and cardiac
motion-correction in 18F Sodium Fluoride (18F-NaF) PET. METHODS: Twenty-two
patients underwent 18F-NaF PET within 22 days of an acute coronary syndrome.
Optimal reconstruction parameters were determined in a subgroup of six patients.
Motion-correction was performed on ECG-gated data of all patients with optimal
reconstruction. Tracer uptake was quantified in culprit and reference lesions by
computing signal-to-noise ratio (SNR) in diastolic, summed, and motion-corrected
images. RESULTS: Reconstruction using 24 subsets, 4 iterations, point-spread
function modelling, time of flight, and 5-mm post-filtering provided the highest
median SNR (31.5) compared to 4 iterations 0-mm (22.5), 8 iterations 0-mm (21.1),
and 8 iterations 5-mm (25.6; all P < .05). Motion-correction improved SNR of
culprit lesions (n = 33) (24.5[19.9-31.5]) compared to diastolic (15.7[12.4
18.1]; P < .001) and summed data (22.1[18.9-29.2]; P < .001). Motion-correction
increased the SNR difference between culprit and reference lesions (10.9[6.3
12.6]) compared to diastolic (6.2[3.6-10.3]; P = .001) and summed data (7.1 [4.8
11.6]; P = .001). CONCLUSIONS: The number of iterations and extent of post
filtering has marked effects on coronary 18F-NaF PET quantification. Cardiac
motion-correction improves discrimination between culprit and reference lesions.
PMID- 29948890
TI - Risk stratification based on J-ACCESS risk models with myocardial perfusion
imaging: Risk versus outcomes of patients with chronic kidney disease.
AB - BACKGROUND: This study aimed to validate the accuracy of major-event risk models
created in the multicenter J-ACCESS prognostic study in a new cohort of patients
with chronic kidney disease (CKD). METHODS AND RESULTS: Three multivariable J
ACCESS risk models were created to predict major cardiac events (cardiac death,
non-fatal acute coronary syndrome, and severe heart failure requiring
hospitalization): Model 1, four variables of age, summed stress score, left
ventricular ejection fraction and diabetes; Model 2 with five variables including
estimated glomerular filtration rate (eGFR, continuous); and Model 3 with
categorical eGFR. The validation data used three-year (3y) cohort of patients
with CKD (n = 526, major events 11.2%). Survival analysis of low (< 3%/3y),
intermediate (3% to 9%/3y), and high (> 9%/3y)-risk groups showed good
stratification by all three models (actual event rates: 3.1%, 9.9%, and 15.9% in
the three groups with eGFR >= 15 mL/min/1.73 m2, P = .0087 (Model 2). However,
actual event rates were equally high across all risk groups of patients with eGFR
< 15 mL/min/1.73 m2. CONCLUSION: The J-ACCESS risk models can stratify patients
with CKD and eGFR >= 15 mL/min/1.73 m2, but patients with eGFR < 15 mL/min/1.73
m2 are potentially at high risk regardless of estimated risk values.
PMID- 29948891
TI - Diagnosis of infection in patients with left ventricular assist device: PET or
SPECT?
PMID- 29948892
TI - Infections in patients using ventricular-assist devices: Comparison of the
diagnostic performance of 18F-FDG PET/CT scan and leucocyte-labeled scintigraphy.
AB - BACKGROUND: The usage of left-ventricular-assist device (LVAD) is increasing in
patients presenting with advanced heart failure. However, device-related
infections are a challenge to recognize and to treat, with an important morbidity
and mortality rate. The role of nuclear medicine imaging remains not well
established for LVAD infections. The present study compared the accuracy of
positron emission tomography/computed tomography with 18F-fludeoxyglucose (18F
FDG PET/CT) and radiolabeled leucocyte scintigraphy for the diagnosis of
infections in patients supported with a continuous-flow LVAD. METHODS: From a
prospectively maintained database, we retrospectively analyzed the diagnostic
performance of radiolabeled leucocyte scintigraphy and 18F-FDG PET/CT in 24
patients who had a LVAD with a suspected device-related infection. Both
examinations were routinely performed in all patients. Infection was assessed by
the International Society for Heart and Lung Transplantation criteria. RESULTS:
Twenty-four patients were included: 15 had a specific VAD infection (5 cardiac
LVAD and 10 driveline), 6 had a VAD-related infection, while 3 patients had a non
VAD-related infection. Sensitivity, specificity, positive predictive value,
negative predictive value, and accuracy were 95.2%, 66.7%, 95.2%, 66.7%, and
91.6%, respectively, for 18F-FDG-PET; and 71.4%, 100%, 100%, 33.3%, and 75%,
respectively, for leucocyte scintigraphy. 18F-FDG PET/CT showed significantly
higher sensitivity (P = 0.01) than leucocyte scintigraphy. CONCLUSION: 18F-FDG
PET/CT and radiolabeled leucocyte scintigraphy single-photon emission computed
tomography carry high performance in the diagnostic of LVAD infections. 18F-FDG
PET/CT shows significantly higher sensitivity and could be proposed as first-line
nuclear medicine procedure.
PMID- 29948893
TI - Are you stressed?
PMID- 29948894
TI - Indirect evidence of sympathetic stimulation by regadenoson.
PMID- 29948895
TI - Opening the door to noninvasive assessment of cardiac transplant rejection: It's
all in the preparation.
PMID- 29948896
TI - 18F-fluorodeoxyglucose use after cardiac transplant: A comparative study of
suppression of physiological myocardial uptake.
AB - BACKGROUND: 18F-fluorodeoxyglucose (FDG) has been useful in the evaluation of
myocardial inflammatory processes. However, it is challenging to identify them
due to physiological 18F-FDG uptake. There are no publications demonstrating the
application of FDG in post-transplant rejection in humans yet. The aim of this
study is to determine the feasibility of suppression of myocardial FDG uptake in
post-transplant patients, comparing three different protocols of preparation.
METHODS: Ten patients after heart transplantation were imaged by FDG associated
with three endomyocardial biopsies (EMB), scheduled in the first year after the
procedure. Before each imaging, patients were randomized to one of three
preparations: (1) hyperlipidic-hypoglycemic diet; (2) fasting longer than 12
hours; and (3) fasting associated with intravenous heparin. All patients would
undergo the three methods. FDG images were analyzed using visual analysis scores
and relative radiotracer cardiac uptake (RRCU). RESULTS: The suppression rate of
radiotracer activity ranged from 55% to 62%. Visual analysis showed that
preparation 3 presented less efficacy in the suppression compared to the others.
However, RRCU did not show difference between the preparations. CONCLUSIONS:
Suppression of physiological myocardial FDG uptake after cardiac transplantation
is feasible. The usefulness of heparin in the suppression is unclear.
PMID- 29948897
TI - A quick glance at selected topics in this issue.
AB - "A quick glance at selected topics in this issue" aims to highlight contents of
the Journal and provide a quick review to the readers.
http://mc.manuscriptcentral.com/jnc .
PMID- 29948898
TI - Are there any guarantees with the warranty period for normal stress SPECT
myocardial perfusion imaging?
PMID- 29948899
TI - N-terminal domain of the RNA polymerase of very virulent infectious bursal
disease virus contributes to viral replication and virulence.
PMID- 29948900
TI - Characteristics of fecal microbiota in non-alcoholic fatty liver disease
patients.
AB - This study was designed to investigate the gut microbiota of patients with non
alcoholic fatty liver disease. The inclusive and exclusive criteria for NAFLD
patients and healthy subjects were formulated, and detailed clinical data were
collected. The genomic DNA of stool samples were extracted for 16S rDNA
sequencing, and the amplified V4-region was sequenced on the Illumina Miseq
platform. Metastats analysis was performed to identify the differential taxa
between the groups. Redundancy analysis was used to evaluate the association
between gut microbial structure and clinical variables. Thirty NAFLD patients and
37 healthy controls were involved. The 16S rDNA sequencing showed that there was
a dramatic variability of the fecal microbiota among all the individuals.
Metastats analysis identified eight families and 12 genera with significant
differences between the two groups. When some clinical parameters, such as waist
to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA
IR), were enrolled in Redundancy analysis, the distribution of the two group of
samples was obviously changed. The compositional shifts in fecal bacterial
communities of NAFLD patients from the healthy controls were mainly at family or
genus levels. According to our Redundancy analysis, insulin resistance and
obesity might be closely related to both NAFLD phenotype and intestinal
microecology.
PMID- 29948901
TI - The miR-58 microRNA family is regulated by insulin signaling and contributes to
lifespan regulation in Caenorhabditis elegans.
AB - microRNAs regulate diverse biological processes such as development and aging by
promoting degradation or inhibiting translation of their target mRNAs. In this
study, we have found that the miR-58 family microRNAs regulate lifespan in C.
elegans. Intriguingly, members of the miR-58 family affect lifespan differently,
sometimes in opposite directions, and have complex genetic interactions. The
abundances of the miR-58 family miRNAs are up-regulated in the long-lived daf-2
mutant in a daf-16-dependent manner, indicating that these miRNAs are effectors
of insulin signaling in C. elegans. We also found that miR-58 is regulated by
insulin signaling and partially required for the lifespan extension mediated by
reduced insulin signaling, germline ablation, dietary restriction, and mild
mitochondrial dysfunction. We further identified the daf-21, ins-1, and isw-1
mRNAs as endogenous targets of miR-58. Our study shows that miRNAs function in
multiple lifespan extension mechanisms, and that the seed sequence is not the
dominant factor defining the role of a miRNA in lifespan regulation.
PMID- 29948902
TI - Assessing the genetic diversity of the critically endangered Chinese sturgeon
Acipenser sinensis using mitochondrial markers and genome-wide single-nucleotide
polymorphisms from RAD-seq.
AB - As a living fossil, the endangered Chinese sturgeon (Acipenser sinensis) has been
considered a national treasure in China. Here, the famous Gezhouba Dam and Three
Gorges Dam on the Yangtze River were built in 1988 and 2006, for economic
purposes. The natural population of Chinese sturgeon has declined since then, as
these dams block its migratory route to the original spawning grounds in the
middle reaches of the Yangtze River. In 2013 and 2014, there was an absence of
spawning where it typically happened near the Gezhouba Dam. Nevertheless, from
April to June in 2015, over 1,000 larvae with different body lengths (10-35 cm)
were detected along the Shanghai Yangtze Estuary; but only little is currently
known about the population genetic structure of the Chinese sturgeon. Herein, we
inferred population genetic parameters from 462 available Chinese sturgeon
specimens based on a 421-bp fragment of the mitochondrial DNA (mtDNA) D-loop
region and 1,481,620 SNPs (single-nucleotide polymorphisms) generated by
restriction site-associated DNA sequencing (RAD-seq). For the D-loop dataset, 15
haplotypes were determined. Randomly picked 23 individuals, representing the 15 D
loop haplotype groups, were subsequently used for further RAD-seq validation. The
average nucleotide diversity calculated from the mtDNA and RAD datasets was
0.0086 and 0.000478, respectively. The overall effective female population size
was calculated to be 1,255 to 2,607, and the long-term effective population size
was estimated to range from 11,950 to 119,500. We observed that the genetic
variability and the effective female population size of the current population in
the Yangtze River are severely low, which are similar to the data reported over
10 years ago. The deduced relatively small effective population of female fish,
limiting the genetic connectivity among Chinese sturgeon, should be considered a
serious threat to this endangered species.
PMID- 29948903
TI - Episodic memory decline in Parkinson' s disease: relation with white matter
hyperintense lesions and influence of quantification method.
AB - The relation of white matter hyperintense lesions to episodic memory impairment
in patients with Parkinson's disease (PD) is still controversial. We aimed at
evaluating the relation between white matter hyperintense lesions and episodic
memory decline in patients with PD. In this multicentric prospective study,
twenty-one normal controls, 15 PD patients without mild cognitive impairment
(MCI) and 13 PD patients with MCI were selected to conduct a clinico-radiological
correlation analysis. Performance during episodic memory testing, age-related
white matter changes score, total manual and automated white matter hyperintense
lesions volume and lobar white matter hyperintense lesions volumes were compared
between groups using the Kruskal-Wallis and Wilcoxon signed-rank tests, and
correlations were assessed using the Spearman test. MCI PD patients had impaired
free recall. They also had higher total, left prefrontal and left temporal white
matter hyperintense lesions volumes than normal controls. Free recall performance
was negatively correlated with the total white matter hyperintense lesions
volume, either manually or automatically delineated, but not with the age-related
white matter changes score. Using automated segmentation, both the left
prefrontal and temporal white matter hyperintense lesions volumes were negatively
correlated with the free recall performance. Early episodic memory impairment in
MCI PD patients may be related to white matter hyperintense lesions, mainly in
the prefrontal and temporal lobes. This relation is influenced by the method used
for white matter hyperintense lesions quantification. Automated volumetry allows
for detecting those changes.
PMID- 29948904
TI - Structural changes in brain regions involved in executive-control and self
referential processing after sleeve gastrectomy in obese patients.
AB - Obesity-related brain gray (GM) and white matter (WM) abnormalities have been
reported in regions associated with food-intake control and cognitive-emotional
regulation. Bariatric surgery (BS) is the most effective way to treat obesity and
induce structural recovery of GM/WM density and WM integrity. It is unknown
whether the surgery can promote structural changes in cortical morphometry along
with weight-loss. Structural Magnetic Resonance Imaging and surface-based
morphometry analysis were used to investigate BS-induced alterations of cortical
morphometry in 22 obese participants who were tested before and one month post
BS, and in 21 obese controls (Ctr) without surgery who were tested twice
(Baseline and One-month). Results showed that fasting plasma ghrelin, insulin,
and leptin levels were significantly reduced post-BS (P < 0.001). Post-BS there
were significant decreases in cortical thickness in the precuneus (PFDR < 0.05)
that were associated with decreases in BMI. There were also significant increases
post-BS in cortical thickness in middle (MFG) and superior (SFG) frontal gyri,
superior temporal gyrus (STG), insula and ventral anterior cingulate cortex
(vACC); and in cortical volume in left postcentral gyrus (PostCen) and vACC (PFDR
< 0.05). Post-BS changes in SFG were associated with decreases in BMI. These
findings suggest that structural changes in brain regions implicated in executive
control and self-referential processing are associated with BS-induced weight
loss.
PMID- 29948905
TI - Loss of white matter connections after severe traumatic brain injury (TBI) and
its relationship to social cognition.
AB - Adults with severe traumatic brain injury (TBI) often suffer poor social
cognition. Social cognition is complex, requiring verbal, non-verbal, auditory,
visual and affective input and integration. While damage to focal temporal and
frontal areas has been implicated in disorders of social cognition after TBI, the
role of white matter pathology has not been examined. In this study 17 adults
with chronic, severe TBI and 17 control participants underwent structural MRI
scans and Diffusion Tensor Imaging. The Awareness of Social Inference Test
(TASIT) was used to assess their ability to understand emotional states,
thoughts, intentions and conversational meaning in everyday exchanges. Track
based spatial statistics were used to perform voxelwise analysis of Fractional
Anisotropy (FA) and Mean Diffusivity (MD) of white matter tracts associated with
poor social cognitive performance. FA suggested a wide range of tracts were
implicated in poor TASIT performance including tracts known to mediate, auditory
localisation (planum temporale) communication between nonverbal and verbal
processes in general (corpus callosum) and in memory in particular (fornix) as
well as tracts and structures associated with semantics and verbal recall (left
temporal lobe and hippocampus), multimodal processing and integration (thalamus,
external capsule, cerebellum) and with social cognition (orbitofrontal cortex,
frontopolar cortex, right temporal lobe). Even when controlling for non-social
cognition, the corpus callosum, fornix, bilateral thalamus, right external
capsule and right temporal lobe remained significant contributors to social
cognitive performance. This study highlights the importance of loss of white
matter connectivity in producing complex social information processing deficits
after TBI.
PMID- 29948906
TI - Identifying disease-related subnetwork connectome biomarkers by sparse hypergraph
learning.
AB - The functional brain network has gained increased attention in the neuroscience
community because of its ability to reveal the underlying architecture of human
brain. In general, majority work of functional network connectivity is built
based on the correlations between discrete-time-series signals that link only two
different brain regions. However, these simple region-to-region connectivity
models do not capture complex connectivity patterns between three or more brain
regions that form a connectivity subnetwork, or subnetwork for short. To overcome
this current limitation, a hypergraph learning-based method is proposed to
identify subnetwork differences between two different cohorts. To achieve our
goal, a hypergraph is constructed, where each vertex represents a subject and
also a hyperedge encodes a subnetwork with similar functional connectivity
patterns between different subjects. Unlike previous learning-based methods, our
approach is designed to jointly optimize the weights for all hyperedges such that
the learned representation is in consensus with the distribution of phenotype
data, i.e. clinical labels. In order to suppress the spurious subnetwork
biomarkers, we further enforce a sparsity constraint on the hyperedge weights,
where a larger hyperedge weight indicates the subnetwork with the capability of
identifying the disorder condition. We apply our hypergraph learning-based method
to identify subnetwork biomarkers in Autism Spectrum Disorder (ASD) and Attention
Deficit Hyperactivity Disorder (ADHD). A comprehensive quantitative and
qualitative analysis is performed, and the results show that our approach can
correctly classify ASD and ADHD subjects from normal controls with 87.65 and
65.08% accuracies, respectively.
PMID- 29948907
TI - Encoding the local connectivity patterns of fMRI for cognitive task and state
classification.
AB - In this work, we propose a novel framework to encode the local connectivity
patterns of brain, using Fisher vectors (FV), vector of locally aggregated
descriptors (VLAD) and bag-of-words (BoW) methods. We first obtain local
descriptors, called mesh arc descriptors (MADs) from fMRI data, by forming local
meshes around anatomical regions, and estimating their relationship within a
neighborhood. Then, we extract a dictionary of relationships, called brain
connectivity dictionary by fitting a generative Gaussian mixture model (GMM) to a
set of MADs, and selecting codewords at the mean of each component of the
mixture. Codewords represent connectivity patterns among anatomical regions. We
also encode MADs by VLAD and BoW methods using k-Means clustering. We classify
cognitive tasks using the Human Connectome Project (HCP) task fMRI dataset and
cognitive states using the Emotional Memory Retrieval (EMR). We train support
vector machines (SVMs) using the encoded MADs. Results demonstrate that, FV
encoding of MADs can be successfully employed for classification of cognitive
tasks, and outperform VLAD and BoW representations. Moreover, we identify the
significant Gaussians in mixture models by computing energy of their
corresponding FV parts, and analyze their effect on classification accuracy.
Finally, we suggest a new method to visualize the codewords of the learned brain
connectivity dictionary.
PMID- 29948908
TI - Gill Morphology and Na+/K+-ATPase Activity of Gobionellus oceanicus (Teleostei:
Gobiidae) in an Estuarine System.
AB - Gobionellus oceanicus is a species widely distributed on the Atlantic coast and
may be susceptible to anthropic effects. This study evaluated the morphology and
the Na+/K+-ATPase activity of G. oceanicus gills considering the concentration of
metals in the fish and Subae River estuary. Although the metal concentrations
detected in the water and sediment did not exceed certain limits, CONAMA
(Brazilian Environment Council), TEL (Threshold Effect Level), and PEL (Probable
Effect Level), the metals levels in gills plus muscle and skin of G. oceanicus
were above the permitted setting of the Ministry of Health, Brazil. The pavement
epithelial cells (PVC) of the gill filament was observed that there were long
microridges either in the apical surface or in the lamella; especially,
microridges degeneration was shown in some PVC from filament epithelium. The
number of ionocyte and the volume density were (0.02 +/- 0.001)/MUm and (0.38 +/-
0.27) %, respectively. The activity of Na+/K+-ATPase was 1.13 +/- 0.76 MUM Pi mg
protein-1 h-1. We describe the volume density and number of ionocytes and Na+/K+
ATPase enzymatic activity in G. oceanicus for the first time, which is useful for
basic and comparative future studies to support aquatic biomonitoring.
PMID- 29948909
TI - Investigations of Human Fascia Lata Elemental Composition-the Effect of Different
Preservation and Mineralisation Methods.
AB - Influence of fixation medium and storage conditions as well as impact of sample
mineralisation procedure on determination of minerals in human fascia lata was
examined and discussed. Freezing and storage in 10% neutral buffered formalin
solution and in 2.5% glutaraldehyde were used as the preservation methods of the
samples. The concentrations of, both essential and toxic, elements were measured
by ICP-OES method in fascia lata samples mineralised with concentrated nitric
acid in a closed microwave system and in open vessels heated on a hot plate.
Freezing was found as the best preserving method of fascia lata samples because
of the number of elements determined and determination precision. The trace
element (Cd, Cr, Cu, Fe, Ni, Sr, Zn) concentrations obtained in samples
decomposed using the conventional hot plate were different from analogous
measurements in solutions obtained after application of closed vessels and
microwave energy assistance. Differences between the mineral compositions of
fascia samples variously preserved and mineralised were statistically evaluated
and discussed. Interelement correlations were analysed taking into account an
impact of various methods of sample conservation. Strong, positive association
between element content was discovered for Cr-Ba, Mn-Ba, P-Ba, Sr-Ba, Sr-Ca, Zn
Ca, Mn-Cr, Pb-Cr, Sr-Cr, Mg-Fe, P-Fe, Pb-Ni, Ti-Ni and Sr-P pairs of elements.
PMID- 29948910
TI - Green Synthesis of Chromium Nanoparticles and Their Effects on the Growth of the
Prawn Macrobrachium rosenbergii Post-larvae.
AB - This study deals with synthesis of chromium nanoparticles (CrNPs) from potassium
dichromate using the aqueous extract of Allium sativum. They were characterized
through UV-VIS light, FE-SEM, EDX, XRD, and FT-IR, which revealed uniform, mono
dispersive, and highly stable CrNPs of 31-64-nm size. The Artemia nauplii was
enriched with 4.94 mg/L of CrNPs (24-h LC50) at different durations (1/2, 1, 2,
and 4 h) and then fed to Macrobrachium rosenbegii post-larvae (PL) for 30 days as
live feed. The results showed that 1/2- and 1-h enriched Artemia nauplii led to
significant improvements in nutritional indices including growth and survival,
and concentrations of tissue biochemical constituents, such as total protein,
amino acid, carbohydrate, and lipid of M. rosenbergii PL (P < 0.05), which
suggests that this concentration of CrNPs was non-toxic to M. rosenbergii PL.
This was confirmed by the insignificant alterations recorded in activities of SOD
and CAT (P > 0.05) in M. rosenbergii PL fed with 1/2- and 1-h enriched Artemia
nauplii as live feed. After that, SOD and CAT activities started to increase.
Therefore, this optimized concentration of CrNPs (4.94 mg/L) is recommended for
enrichment of Artemia nauplii for 1/2-1-h duration as a sustainable material in
the nursery of M. rosenbergii.
PMID- 29948911
TI - Mineral and Trace Metal Concentrations in Seaweeds by Microwave-Assisted
Digestion Method Followed by Quadrupole Inductively Coupled Plasma Mass
Spectrometry.
AB - This study reports the total concentrations of mineral and trace metals sodium,
potassium, calcium, magnesium, phosphorus, iron, copper, zinc, and manganese in
the seaweeds Padina tetrastromatica, Turbinaria ornate, Sargassum wightii,
Sargassum swartzii, Gracilaria edulis, Ulva lactuca, Chaetomorpha antennina, and
Halimeda opuntia collected from mandapam coastal regions, Southeast coast of
India. Microwave-assisted digestion was used for sample preparation prior to
mineral and trace metal analysis. Mineral and trace metal analyses were
determined by inductively coupled plasma mass spectrometry. The ranges of
concentrations of mineral and trace metals in algae were 27.04 +/- 2.54-194.08 +/
2.36 mg/kg for manganese, 1.88 +/- 0.10-121.5 +/- 0.70 mg/kg for sodium, 6.5 +/-
0.56-90.5 +/- 2.12 mg/kg for magnesium, 59.07 +/- 0.34-672 +/- 2.82 mg/kg for
potassium, 13.15 +/- 2.08-135.13 +/- 1.59 for sulfur, 0.003 +/- 0.001-3.44 +/-
0.13 mg/kg for cobalt, 0.39 +/- 0.19-8.95 +/- 0.38 mg/kg for copper, 0.72 +/-
0.28-25.72 +/- 0.39 mg/kg for zinc, and 6.01 +/- 0.27-188.47 +/- 1.92 mg/kg for
iron.The results were evaluated statistically, and the significant difference was
observed in the mean concentrations of all mineral and trace elements, except Co,
Cu, and Zn, among the type of seaweeds.
PMID- 29948912
TI - Assessment of Toxic Metals and Hazardous Substances in Tattoo Inks Using Sy-XRF,
AAS, and Raman Spectroscopy.
AB - Synchrotron radiation X-ray fluorescence spectroscopy, in conjunction with atomic
absorption and Raman spectroscopy, was used to analyze a set of top brand tattoo
inks to investigate the presence of toxic elements and hazardous substances. The
Cr, Cu, and Pb contents were found to be above the maximum allowed levels
established by the Council of Europe through the resolution ResAP(2008)1 on
requirements and criteria for the safety of tattoos and permanent makeup. Raman
analysis has revealed the presence of a set of prohibited substances mentioned in
ResAP(2008)1, among which are the pigments Blue 15, Green 7, and Violet 23. Other
pigments that were identified in white, black, red, and yellow inks are the
Pigment White 6, Carbon Black, Pigment Red 8, and a diazo yellow, respectively.
The present results show the importance of regulating tattoo ink composition.
PMID- 29948913
TI - The Importance of Se-Related Genes in the Chondrocyte of Kashin-Beck Disease
Revealed by Whole Genomic Microarray and Network Analysis.
AB - Kashin-Beck disease (KBD) is an endemic, chronic, and degenerative
osteoarthropathy. Selenium (Se) deficiency plays important role in the
pathogenesis of KBD. We aimed to screen Se-related gene from chondrocytes of
patients with KBD. Whole-genome oligonucleotide microarrays were used to detect
differentially expressed genes. qRT-PCR was used to confirm the microarray
results. Comparative Toxicogenomics Database (CTD) was used to screen Se-related
genes from differentially expressed genes. Gene Ontology (GO) classifications and
network analysis of Se-related genes were constituted by STRING online system.
Three hundred ninety-nine differentially expressed genes were obtained from
microarray. Among them, 54 Se-related genes were identified by CTD. The qRT-PCR
validation showed that four genes expressed similarly with the ones in the
microarray transcriptional profiles. The Se-related genes were categorized into 6
cellular components, 8 molecular functions, 44 biological processes, 10 pathways,
and 1 network by STRING. The Se-related gene insulin-like growth factor binding
protein 2 (IGFBP2), insulin-like growth factor binding protein 3 (IGFBP3),
interleukin 6 (IL6), BCL2, apoptosis regulator (BCL2), and BCL2-associated X,
apoptosis regulator (BAX), which involved in many molecular functions, biological
processes, and apoptosis pathway may play important roles in the pathogenesis of
KBD.
PMID- 29948914
TI - Iron Accumulation Leads to Bone Loss by Inducing Mesenchymal Stem Cell Apoptosis
Through the Activation of Caspase3.
AB - Osteoporosis (OP) is a disease associated with bone loss and microstructure
degradation. Recent studies have shown that iron accumulation may be a risk
factor for OP. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells
and precursors to osteoblasts. MSCs play an important role in OP. Therefore, we
evaluated the correlation between MSCs and OP in an environment of iron
accumulation. Serum P1NP was decreased in iron accumulation mice. Micro-CT
revealed that iron accumulation decreased bone mineral density and spatial
structural parameters. Iron accumulation inhibited MSC quantity in bone marrow.
However, the iron chelator deferoxamine (DFO) rescued the suppression. Iron
accumulation also changed the MSC cell cycle. Iron elevated MSC cell ROS level
and NOX4 protein expression. MSC apoptosis was increased, and more caspase3 was
cleaved after iron intervention. Our data suggests that iron accumulation
inhibits MSC quantity and induces MSC apoptosis. Bone loss from iron accumulation
may correlate with the inhibition of MSCs.
PMID- 29948915
TI - The Effect of Maternal Supplementation of Zinc, Selenium, and Cobalt as Slow
Release Ruminal Bolus in Late Pregnancy on Some Blood Metabolites and Performance
of Ewes and Their Lambs.
AB - The aim of this study was to determine the effect of the supplementation of a
slow-release bolus of zinc (Zn), selenium (Se), and cobalt (Co) at late gestation
(6 week prepartum) on performance and some blood metabolites of Mehraban ewes and
their lambs until weaning. Seventy pregnant ewes, 6 weeks prior to expected
lambing, were randomly divided into two groups (35 heads each) including (1)
control group and (2) slow-release bolus group. Blood samples of ewes were
obtained on day 10 prepartum and 45 and 90 days postpartum, and milk samples were
collected on day 45. Blood samples of lambs were collected on days 10, 45, and
90. Body weight at birth and weaning and average daily gain were higher and
percentage of mortality and white muscle disease rate were lower in lambs whose
mothers were given a bolus (P < 0.05). Slow-release bolus administration
increased serum alkaline phosphatase and whole blood glutathione peroxidase
activity, plasma concentrations of Zn, Se, and vitamin B12 in ewes and their
lambs (P < 0.05). In addition, serum creatine phosphokinase activity of lambs
whose mothers were given bolus was lower (P < 0.05). Serum concentration of T3 in
bolus given ewes and their lambs was higher (P < 0.05) and serum T4 concentration
was lower (P < 0.05). Zinc, Se, and vitamin B12 concentrations in milk were
significantly higher in treated ewes (P < 0.05). Obtained results showed that
maternal supplementation of zinc, selenium, and cobalt as slow-release ruminal
bolus in late pregnancy improved some mineral status of ewes and their lambs
until weaning and led to higher body weights of lambs at weaning.
PMID- 29948916
TI - Extended release delivery system of metoprolol succinate using hot-melt
extrusion: effect of release modifier on methacrylic acid copolymer.
AB - The current study reports on the manufacturing of extended release dosage forms
of metoprolol succinate via hot-melt extrusion (HME) technology. Either
Eudragit(r)S100 and Eudragit(r)L100 alone or in combination with release
modifying agent PolyoxTM WSR 303 and Eudragit(r)L100-55 were processed to obtain
complete and faster release. Metoprolol succinate with similar solubility
parameters to polymer was dispersed in polymer matrix and was characterized by
Fourier transform infrared spectroscopy (FT-IR), differential scanning
calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy
(SEM). Stability of drug after extrusion was confirmed by thermogravimetric
analysis and high-performance liquid chromatography. Physical characterization
method exhibited that the drug was homogeneously dispersed in non-crystalline
state in Eudragit(r)L100-55-based formulations whereas in semi-crystalline state
in PolyoxTM WSR 303. The drug release percentage was below 3 and 40% in 0.1 N HCL
with Eudragit(r)L100-55- and PolyoxTM WSR 303-containing formulations,
respectively, and exhibited pH-dependent dissolution properties. The drug-release
mechanism was anomalous with PolyoxTM WSR 303 formulations whereas diffusion
through pore formation was obtained with Eudragit(r)L100-55. Both Eudragit(r)L100
55 and PolyoxTM WSR 303 changed the release mechanism and kinetics of drug
release from thermally processed dosage forms. The optimized stable formulation
is similar to the marketed formulation with F2 value of 72.36. Thus, it can be
concluded that HME was exploited as an effective process for the preparation of
controlled release matrix system based on pH-dependent polymer matrices
Eudragit(r)S100 and Eudragit(r)L100.
PMID- 29948917
TI - Individually coated microneedles for co-delivery of multiple compounds with
different properties.
AB - Microneedle (MN) patches provide a simple method for delivery of drugs that might
otherwise require hypodermic injection. Conventional MN patch fabrication methods
typically can load only one or possibly multiple miscible agents with the same
formulation on all MNs, which limits the combination and spatial distribution of
drugs and formulations having different properties (such as solubility) in a
single patch. In this study, we coated MNs individually instead of coating all
MNs from the same formulation, making possible a patch where each individual MN
is coated with different formulations and drugs. In this way, individually coated
MN patches co-delivered multiple agents with different physicochemical
characteristics (immiscible molecules, proteins, and nanoparticles) and in
different spatial patterns in the skin. MN loading was adjusted by modifying the
number of coating layers, and co-delivery of multiple agents was demonstrated in
the porcine skin. We conclude that individually coating MNs enables co-delivery
of multiple different compounds and formulations with needle-by-needle spatial
control in the skin.
PMID- 29948918
TI - Oligonucleotide-Based Therapies for Inflammatory Bowel Disease.
AB - The growing understanding of the immunopathogenesis of inflammatory bowel
diseases (IBDs) has contributed to the identification of new targets whose
expression/activity can be modulated for therapeutic purposes. Several approaches
have been employed to develop selective pharmaceutical compounds; among these,
antisense oligonucleotides (ASOs) or synthetic oligonucleotides represent a valid
option for inhibiting or enhancing, respectively, the expression/function of
molecules that have been implicated in the control of IBD-related inflammation.
In this context, data have been accumulated for the following compounds:
alicaforsen, an ASO targeting intercellular adhesion molecule-1, a transmembrane
glycoprotein that regulates rolling and adhesion of leukocytes to inflamed
intestine; DIMS0150 and BL-7040, two oligonucleotides that enhance Toll-like
receptor-9 activity; Mongersen, an ASO that inhibits Smad7, thereby restoring
transforming growth factor-beta1/Smad-associated signaling; STNM01, a double
stranded RNA oligonucleotide silencing carbohydrate sulfotransferase, an enzyme
involved in fibrogenic processes, and hgd40, a specific DNAzyme inhibiting
expression of the transcription factor GATA3. In this article, we review the
rationale and the available data relative to the use of these agents in IBD.
Although pre-clinical and phase II trials in IBD support the use of
oligonucleotide-based therapies for treating the pathogenic process occurring in
the gut of patients with these disorders, further work is needed to establish
whether and which patients can benefit from specific ASOs and identify biomarkers
that could help optimize treatment.
PMID- 29948919
TI - Advances and Limitations of Current Epigenetic Studies Investigating Mammalian
Axonal Regeneration.
AB - Axonal regeneration relies on the expression of regenerative associated genes
within a coordinated transcriptional programme, which is finely tuned as a result
of the activation of several regenerative signalling pathways. In mammals, this
chain of events occurs in neurons following peripheral axonal injury, however it
fails upon axonal injury in the central nervous system, such as in the spinal
cord and the brain. Accumulating evidence has been suggesting that epigenetic
control is a key factor to initiate and sustain the regenerative transcriptional
response and that it might contribute to regenerative success versus failure.
This review will discuss experimental evidence so far showing a role for
epigenetic regulation in models of peripheral and central nervous system axonal
injury. It will also propose future directions to fill key knowledge gaps and to
test whether epigenetic control might indeed discriminate between regenerative
success and failure.
PMID- 29948920
TI - Now is the Critical Time for Engineered Neuroplasticity.
AB - Recent advances in neuroscience and devices are ushering in a new generation of
medical treatments. Engineered biodevices are demonstrating the potential to
create long-term changes in neural circuits, termed neuroplasticity. Thus, the
approach of engineering neuroplasticity is rapidly expanding, building on recent
demonstrations of improved quality of life for people with movement disorders,
epilepsy, and spinal cord injury. In addition, discovering the fundamental
mechanisms of engineered neuroplasticity by leveraging anatomically well
documented systems like the spinal cord is likely to provide powerful insights
into solutions for other neurotraumas, such as stroke and traumatic brain injury,
as well as neurodegenerative disorders, such as Alzheimer's, Parkinson disease,
and multiple sclerosis. Now is the time for advancing both the experimental
neuroscience, device development, and pioneering human trials to reap the
benefits of engineered neuroplasticity as a therapeutic approach for improving
quality of life after spinal cord injury.
PMID- 29948921
TI - Encoding strategies in self-initiated visual working memory.
AB - During a typical day, visual working memory (VWM) is recruited to temporarily
maintain visual information. Although individuals often memorize external visual
information provided to them, on many other occasions they memorize information
they have constructed themselves. The latter aspect of memory, which we term self
initiated WM, is prevalent in everyday behavior but has largely been overlooked
in the research literature. In the present study we employed a modified change
detection task in which participants constructed the displays they memorized, by
selecting three or four abstract shapes or real-world objects and placing them at
three or four locations in a circular display of eight locations. Half of the
trials included identical targets that participants could select. The results
demonstrated consistent strategies across participants. To enhance memory
performance, participants reported selecting abstract shapes they could
verbalize, but they preferred real-world objects with distinct visual features.
Furthermore, participants constructed structured memory displays, most frequently
based on the Gestalt organization cue of symmetry, and to a lesser extent on cues
of proximity and similarity. When identical items were selected, participants
mostly placed them in close proximity, demonstrating the construction of
configurations based on the interaction between several Gestalt cues. The present
results are consistent with recent findings in VWM, showing that memory for
visual displays based on Gestalt organization cues can benefit VWM, suggesting
that individuals have access to metacognitive knowledge on the benefit of
structure in VWM. More generally, this study demonstrates how individuals
interact with the world by actively structuring their surroundings to enhance
performance.
PMID- 29948922
TI - Systems biology of eukaryotic superorganisms and the holobiont concept.
AB - The founders of modern biology (Jean Lamarck, Charles Darwin, August Weismann
etc.) were organismic life scientists who attempted to understand the morphology
and evolution of living beings as a whole (i.e., the phenotype). However, with
the emergence of the study of animal and plant physiology in the nineteenth
century, this "holistic view" of the living world changed and was ultimately
replaced by a reductionistic perspective. Here, I summarize the history of
systems biology, i.e., the modern approach to understand living beings as
integrative organisms, from genotype to phenotype. It is documented that the
physiologists Claude Bernard and Julius Sachs, who studied humans and plants,
respectively, were early pioneers of this discipline, which was formally founded
50 years ago. In 1968, two influential monographs, authored by Ludwig von
Bertalanffy and Mihajlo D. Mesarovic, were published, wherein a "systems theory
of biology" was outlined. Definitions of systems biology are presented with
reference to metabolic or cell signaling networks, analyzed via genomics,
proteomics, and other methods, combined with computer simulations/mathematical
modeling. Then, key insights of this discipline with respect to epiphytic
microbes (Methylobacterium sp.) and simple bacteria (Mycoplasma sp.) are
described. The principles of homeostasis, molecular systems energetics,
gnotobiology, and holobionts (i.e., complexities of host-microbiota interactions)
are outlined, and the significance of systems biology for evolutionary theories
is addressed. Based on the microbe-Homo sapiens-symbiosis, it is concluded that
human biology and health should be interpreted in light of a view of the
biomedical sciences that is based on the holobiont concept.
PMID- 29948923
TI - The Transcriptional Regulatory Properties of Amyloid Beta 1-42 may Include
Regulation of Genes Related to Neurodegeneration.
AB - Our previous study demonstrated the translocation of Abeta1-42 to the nucleus in
response to antibiotic treatment, and interpreted it as a possible
transcriptional response of Abeta1-42 to antibiotics. The present study aims to
investigate how amyloid acts on the key elements of neurodegeneration and the
molecules involved in the induction of Abeta1-42 production. For this purpose, we
investigated the acute effect of Abeta1-42 on the transcriptional levels of genes
that have roles in the mechanisms that produce Abeta itself: alpha secretase
(ADAM10), beta secretase (BACE1), the gamma secretase complex (PS-1, PS-2,
Nicastrin), the substrate APP, APOE (the significant risk factor for sporadic
form of the AD), TREM2 (recently indicated as a contributor to AD risk), NMDAR
subunits and PKCzeta (contributors of memory and learning), and key elements of
tau pathology such as tau, GSK3alpha, GSK3beta, and Cdk5. Additionally, we
examined cholecalciferol metabolism-related enzyme 1alpha-hydroxylase
(1alphaOHase) in primary cortical neurons with qRT-PCR. Our results indicate that
Abeta1-42 has an effect on most of the target genes. This effect involves
regulation of the amyloidogenic pathway in a complex manner, specifically, a
general downregulation in NMDARs, ApoE, Trem2, and 1alphaOHase genes, and general
up-regulation of tau pathway-related genes. We speculate that the presence of
Abeta impacts the neurons not only with toxic events but also at the
transcriptional level. The nuclear localization of Abeta1-42 and its regulatory
effects on the target genes that we investigated in present study indicates
Abeta1-42 as a transcriptional regulator of genes related to neurodegeneration.
PMID- 29948924
TI - Social Media as a Tool to Promote Health Awareness: Results from an Online
Cervical Cancer Prevention Study.
AB - Online social media platforms represent a promising opportunity for public health
promotion. Research is limited, however, on the effectiveness of social media at
improving knowledge and awareness of health topics and motivating healthy
behavior change. Therefore, we investigated whether participation in an online
social media platform and receipt of brief, tailored messages is effective at
increasing knowledge, awareness, and prevention behaviors related to human
papillomavirus (HPV) and cervical cancer. We conducted an online study in which
782 recruited participants were consecutively assigned to nine-person groups on a
social media platform. Participants were shown a unique random set of 20 tailored
messages per day over five days. Participants completed a baseline and post
survey to assess their knowledge, awareness, and prevention behaviors related to
HPV and cervical cancer. There were no statistically significant changes in
knowledge and prevention behaviors from the baseline to the post survey among
study participants. There was a modest, statistically significant change in
response to whether participants had ever heard of HPV, increasing from 90 to 94%
(p = 0.003). Our findings suggest that most study participants had substantial
knowledge, awareness, and engagement in positive behaviors related to cervical
cancer prevention at the start of the study. Nevertheless, we found that HPV
awareness can be increased through brief participation in an online social media
platform and receipt of tailored health messages. Further investigation that
explores how social media can be used to improve knowledge and adoption of
healthy behaviors related to cervical cancer is warranted.
PMID- 29948925
TI - Survivorship Care Plan Implementation in US Cancer Programs: a National Survey of
Cancer Care Providers.
AB - Survivorship care plans (SCPs)-documents intended to improve care for cancer
survivors who have completed active treatment-are required, yet implementation is
poor. We sought to understand SCP implementation in cancer programs in the USA
with the objective of identifying opportunities for improvement. We recruited
cancer care providers in the USA via several cancer care networks to participate
in a survey regarding SCP implementation. We used descriptive statistics to
analyze the data. Three hundred ninety-five providers from diverse cancer
programs in 47 states and Washington, DC responded to the survey. The timing of
SCP implementation varied across and within cancer programs, with approximately
40% of respondents reporting developing SCPs more than 3 months after primary
treatment or adjuvant therapy completion. Nurse navigators were responsible for
48-58% of each stage of SCP implementation. Processes that could have been
automated often occurred in-person or via phone and vice versa. Respondents
reported spending more than 2 h per SCP to complete all stages of implementation,
of which less than a third was reimbursed by third-party payers. We identified
several opportunities for improving SCP implementation, including broadening the
base of responsibility, optimizing modes of communication, decreasing the time
required and increasing the funding available, and limiting variation in SCP
implementation across and within cancer programs. Future work should assess the
influence of approaches to SCP implementation on desired outcomes.
PMID- 29948926
TI - Consequences of Biomarker Analysis on the Cost-Effectiveness of Cetuximab in
Combination with FOLFIRI as a First-Line Treatment of Metastatic Colorectal
Cancer: Personalised Medicine at Work.
AB - BACKGROUND: Therapies may be more efficacious when targeting a patient
subpopulation with specific attributes, thereby enhancing the cost-effectiveness
of treatment. In the CRYSTAL study, patients with metastatic colorectal cancer
(mCRC) were treated with cetuximab plus FOLFIRI or FOLFIRI alone until disease
progression, unacceptable toxic effects or withdrawal of consent. OBJECTIVE: To
determine if stratified use of cetuximab based on genetic biomarker detection
improves cost-effectiveness. METHODS: We used individual patient data from
CRYSTAL to compare the cost-effectiveness, cost per life-year (LY) and cost per
quality-adjusted LY (QALY) gained of cetuximab plus FOLFIRI versus FOLFIRI alone
in three cohorts of patients with mCRC: all randomised patients (intent-to-treat;
ITT), tumours with no detectable mutations in codons 12 and 13 of exon 2 of the
KRAS protein ('KRAS wt') and no detectable mutations in exons 2, 3 and 4 of KRAS
and exons 2, 3 and 4 of NRAS ('RAS wt'). Survival analysis was conducted using
RStudio, and a cost-utility model was modified to allow comparison of the three
cohorts. RESULTS: The deterministic base-case ICER (cost per QALY gained) was
L130,929 in the ITT, L72,053 in the KRAS wt and L44,185 in the RAS wt cohorts for
cetuximab plus FOLFIRI compared with FOLFIRI alone. At a L50,000 willingness-to
pay threshold, cetuximab plus FOLFIRI has a 2.8, 20 and 63% probability of being
cost-effective for the ITT, KRAS wt and RAS wt cohorts, respectively, versus
FOLFIRI alone. CONCLUSION: Screening for mutations in both KRAS and NRAS may
provide the most cost-effective approach to patient selection.
PMID- 29948927
TI - Public's Willingness to Pay Towards a Medical Device for Detecting Foot
Ulceration in People with Diabetes.
AB - OBJECTIVES: Diabetic foot ulceration (DFU) is a common and serious complication
among diabetic patients. A medical device has been developed to prevent the
occurrence of DFU. The aim of this study was to investigate the willingness to
pay (WTP) for this device among the general public in the UK. METHODS: A
contingent valuation survey was administered to 1051 participants through an
online survey including questions on socio-demographic characteristics, self
reported health, knowledge of diabetes and medical devices, and WTP. A two-part
model was used to analyse determinants of WTP, including a logistic model in the
first part and a generalised linear model with a log-transformed WTP in the
second part. RESULTS: More than half (55.9%) of the participants expressed a
positive WTP. The annual mean (standard deviation) and median (interquartile
range) WTP values were L76.9 (69.1) and L50 (80), respectively. Older age, middle
level education, good/excellent self-reported health, visiting doctors once/2-5
times, diabetes experience, medical device experience and more than average self
perceived likelihood of using similar devices were associated with a higher
likelihood of willingness to pay. Younger age, male gender and higher household
income were associated with higher WTP values. CONCLUSION: This study
demonstrated that people are willing to pay for this device and they tend to
contribute when they have experience of diabetes or similar devices and perceive
self-benefit.
PMID- 29948929
TI - Physiological resilience of a temperate soft coral to ocean warming and
acidification.
AB - Atmospheric concentration of carbon dioxide (CO2) is increasing at an
unprecedented rate and subsequently leading to ocean acidification.
Concomitantly, ocean warming is intensifying, leading to serious and predictable
biological impairments over marine biota. Reef-building corals have proven to be
very vulnerable to climate change, but little is known about the resilience of
non-reef-building species. In this study, we investigated the effects of ocean
warming and acidification on the antioxidant enzyme activity (CAT-catalase, and
GST-glutathione S-transferase), lipid peroxidation (using malondialdehyde, MDA
levels as a biomarker) and heat shock response (HSP70/HSC70 content) of the
octocoral Veretillum cynomorium. After 60 days of acclimation, no mortalities
were registered in all treatments. Moreover, CAT and GST activities, as well as
MDA levels, did not change significantly under warming and/or acidification. Heat
shock response was significantly enhanced under warming, but high CO2 did not
have a significant effect. Contrasting to many of their tropical coral-reef
relatives, our findings suggest that temperate shallow-living octocorals may be
able to physiologically withstand future conditions of increased temperature and
acidification.
PMID- 29948930
TI - Treatment of multiresistant prolactinomas with a combination of cabergoline and
octreotide LAR.
AB - BACKGROUND AND OBJECTIVES: Dopamine agonist (DA)-resistant prolactinomas are rare
but they constitute a real challenge, since there are few therapeutic
alternatives left for these patients. DESIGN AND SETTING: Proof-of-concept study
at a tertiary care, referral center. PATIENTS AND METHODS: The studied population
consisted of five patients (one female and four males, mean age at diagnosis 23.5
+/- 19) with macroprolactinomas with persistent hyperprolactinemia and/or tumor
mass despite high doses of cabergoline (CBG) and pituitary surgery, to whom 20 mg
monthly of octreotide LAR was added for 6-13 months. Response was evaluated by
measuring prolactin (PRL) levels and by magnetic resonance imaging.
Immunohistochemistry (IHC) for pituitary hormones, Ki-67, and somatostatin
receptor subtypes 2 and 5 was (SSTR2 and 5) was available in two of the subjects.
RESULTS: The addition of octreotide LAR to ongoing CBG treatment had no effect on
either PRL levels or tumor size in three patients. In two of the five patients,
combination treatment resulted in a significant reduction in PRL concentrations
(from 7643 to 200 ng/mL and from 2587 to 470 ng/mL) as well as in adenoma size
(93% reduction). IHC evaluation of tumor samples from two patients (a responder
and a non-responder) revealed positive immunostaining for PRL and SSTR5 but not
for other pituitary hormones or for SSTR2. CONCLUSIONS: The addition of a
somatostatin analog to ongoing CBG treatment may be effective in some patients
with DA-resistant macroprolactinomas, independently of the adenoma's SSTR
expression profile.
PMID- 29948928
TI - Pediatric Cancer Immunotherapy: Opportunities and Challenges.
AB - Cancer immunotherapies, widely heralded as transformational for many adult cancer
patients, are becoming viable options for selected subsets of pediatric cancer
patients. Many therapies are currently being investigated, from immunomodulatory
agents to adoptive cell therapy, bispecific T-cell engagers, oncolytic
virotherapy, and checkpoint inhibition. One of the most exciting immunotherapies
recently FDA approved is the use of CD19 chimeric antigen receptor T cells for
pre-B-cell acute lymphoblastic leukemia. With this approval and others,
immunotherapy for pediatric cancers is gaining traction. One of the caveats to
many of these immunotherapies is the challenge of predictive biomarkers;
determining which patients will respond to a given therapy is not yet possible.
Much research is being focused on which biomarkers will be predictive and
prognostic for these patients. Despite many benefits of immunotherapy, including
less long-term side effects, some treatments are fraught with immediate side
effects that range from mild to severe, although most are manageable. With few
downsides and the potential for disease cures, immunotherapy in the pediatric
population has the potential to move to the front-line of therapeutic options.
PMID- 29948932
TI - Serum calcitonin gene-related peptide facilitates adipose tissue lipolysis during
exercise via PIPLC/IP3 pathways.
AB - PURPOSE: Calcitonin gene-related peptide (CGRP) is formed by alternative
transcription of the calcitonin/alpha-CGRP gene, which also gives rise to
calcitonin (CT). Recently, CGRP has been the focus of research for its metabolic
effects in vitro. In the present study, the in vivo effects of CGRP on epididymal
fat pads lipolysis at rest and during exercise were investigated in trained male
Wistar rats. METHODS: Male Wistar rats were assigned to control and trained
groups, which underwent endurance training for 12 weeks. The control (at rest)
and trained (during acute exercise) animals were subjected to an intravenous
injection of rat recombinant CGRP (2 ug kg-1) and CGRP-(8-37), a competitive CGRP
receptors antagonist, to evaluate if and how CGRP can affect adipose tissue
lipolysis at rest and during exercise. RESULTS: Intravenous injection of rat CGRP
recombinant at rest upregulated major lipolysis pathways (cyclic AMP (cAMP), AMP
activated protein kinase (AMPK), and phospholipase C (PIPLC/IP3)) in fat pads,
causing an elevation in plasma-free fatty acid (FFA) and a decrease in plasma
triglyceride (TG). All the effects were eliminated by pretreating the animals
with CGRP-(8-37), suggesting that CGRP receptors were necessary for lipolytic
effects of CGRP in fat pads. In trained animals, acute exercise augmented CGRP in
serum, cerebrospinal fluid (CSF), and the cortex. Pretreating the animals with
CGRP-(8-37) attenuated PIPLC/IP3 pathway in fat pads and had no effect on cAMP
and AMPK pathways. CONCLUSIONS: Epididymal fat pads is a metabolic target for
CGRP during exercise and CGRP effects on adipose tissue metabolism during
exercise could be related to PIPLC/IP3 pathway.
PMID- 29948933
TI - Assessing the utility of preoperative serum thyroglobulin in differentiated
thyroid cancer: a retrospective cohort study.
AB - PURPOSE: Serum thyroglobulin (TG) is used to monitor for recurrence or
progression of differentiated thyroid cancer (DTC). The role of preoperative TG
measurement is more ambiguous, yet still being used in some centers. We aimed to
determine whether preoperative TG correlates with disease stage or metastatic
burden. METHODS: A retrospective review of patients with TG measured before
thyroidectomy was conducted. Data collected included demographics, preoperative
TG, pathology, and cancer stage. Associations between preoperative TG levels and
size of largest malignant nodule, thyroid gland size, stage of cancer, and
presence of metastasis using Wilcoxon rank sum tests and Spearman correlations
were performed. Receiver operator curve (ROC) was generated for metastasis
status. RESULTS: Of 598 patients, we excluded those with positive TG antibodies
(n = 176); 422 patients were included in the final analysis. Median age was 55
years and 76% were female. Of 78% with malignancy, papillary thyroid cancer was
the most frequent (92%). 18% had TG levels >500 ng/mL and 29% <45 ng/mL. 4% had
distant metastasis and 18% had lymph node metastasis. Median follow-up was 52
months. Significant positive correlations between preoperative TG and thyroid
size (rho 0.49, p < 0.001), and malignant nodule size (rho 0.27, p < 0.001).
Using a cut-off of 500 ng/mL, sensitivity to detect metastasis was 10.3% (95% CI
2.5-18.2), specificity 90.0% (95% CI 86.0-93.9). The area under curve for ROC
(0.46, 95% CI 0.38-0.54) indicated poor diagnostic ability for metastasis.
CONCLUSION: Although preoperative TG correlated significantly with the size of
the gland and T stage, there was no correlation with metastasis. Preoperative TG
is of limited utility in today's value-based healthcare environment.
PMID- 29948931
TI - Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus
contributes to male hypogonadism caused by high-fat diet-induced obesity.
AB - PURPOSE: Obesity may lead to male hypogonadism, the underlying mechanism of which
remains unclear. In the present study, we established a murine model of male
hypogonadism caused by high-fat diet-induced obesity to verify the following
hypotheses: 1) an increased leptin level may be related to decreased secretion of
GnRH in obese males, and 2) repression of kisspeptin/GPR54 in the hypothalamus,
which is associated with increased leptin levels, may account for the decreased
secretion of GnRH and be involved in secondary hypogonadism (SH) in obese males.
METHODS: Male mice were fed high-fat diet for 19 weeks and divided by body weight
gain into diet-induced obesity (DIO) and diet-induced obesity resistant (DIO-R)
group. The effect of obesity on the reproductive organs in male mice was observed
by measuring sperm count and spermatozoid motility, relative to testis and
epididymis weight, testosterone levels, and pathologic changes. Leptin,
testosterone, estrogen, and LH in serum were detected by ELISA method. Leptin
receptor (Ob-R), Kiss1, GPR54, and GnRH mRNA were measured by real-time PCR in
the hypothalamus. Expression of kisspeptin and Ob-R protein was determined by
Western blotting. Expression of GnRH and GPR54 protein was determined by
immunohistochemical analysis. RESULTS: We found that diet-induced obesity
decreased spermatozoid motility, testis and epididymis relative coefficients, and
plasma testosterone and luteinizing hormone levels. An increased number and
volume of lipid droplets in Leydig cells were observed in the DIO group compared
to the control group. Significantly, higher serum leptin levels were found in the
DIO and DIO-R groups. The DIO and DIO-R groups showed significant downregulation
of the GnRH, Kiss1, GPR54, and Ob-R genes. We also found decreased levels of
GnRH, kisspeptin, GPR54, and Ob-R protein in the DIO and DIO-R groups.
CONCLUSIONS: These lines of evidence suggest that downregulation of Ob-R and
kisspeptin/GPR54 in the murine hypothalamus may contribute to male hypogonadism
caused by high-fat diet-induced obesity.
PMID- 29948934
TI - Increasing soft tissue thickness does not affect trabecular bone score
reproducibility: a phantom study.
AB - PURPOSE: Trabecular Bone Score (TBS) provides an indirect score of trabecular
microarchitecture from lumbar spine (LS) dual energy X-ray absorptiometry.
Increasing soft tissue thickness artifactually reduces TBS values; we evaluated
the effect of a fictitious increase of soft tissue thickness on TBS and bone
mineral density (BMD) reproducibility on a phantom model. METHODS: A Hologic
spine phantom was scanned with a QDR-Discovery W Hologic densitometer. Fresh pork
rind layers of 5 mm were used to simulate the in-vivo soft tissues. For each scan
mode (fast array [FA], array, high definition [HD]), 25 scans were consecutively
performed without phantom repositioning, at 0 (no layers), 1 cm, 3 cm, and 6 cm
of thickness. BMD and TBS reproducibility was calculated as the complement to
100% of least significant change. RESULTS: Both BMD and TBS reproducibility
slightly decreased with increasing soft tissue; this difference was statistically
significant only for BMD using HD modality (reproducibility decreased from 99.4%
at baseline to 98.4% at 6-cm of thickness). TBS reproducibility was slightly
lower compared to that of BMD, and ranged between 98.8% (array, 0 cm) and 97.4%
(FA, 6 cm). Without taking into account manufacturer BMI optimization, we found a
progressive decrease of TBS mean values with increasing soft tissue thickness.
The highest TBS difference between baseline scan and 6 cm was -0.179 (-14.27%)
using HD. CONCLUSIONS: Despite being slightly lower than that of BMD, TBS
reproducibility was not affected up to 6 cm of increasing soft tissue thickness,
and was even less influenced by fat than BMD reproducibility.
PMID- 29948935
TI - TERTp mutation is associated with a shorter progression free survival in patients
with aggressive histology subtypes of follicular-cell derived thyroid carcinoma.
AB - PURPOSE: Evaluate the impact of TERTp mutation on the outcomes after initial
treatment of 45 patients with thyroid carcinomas derived from follicular cells
(TCDFC) with aggressive histology, in which the role of this mutation is not yet
well defined. METHODS: Analysis of the presence of TERTp (-124C > T and -146C >
T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of
their correlation with the patient's outcomes. RESULTS: Forty-five patients with
aggressive histopathologic variants were included in the study. Of these, 68.9%
had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly
differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive
follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell
carcinoma). Lymph node metastases were present in 46.7% and distant metastases in
54.6%. The response to the initial therapy was excellent in 45.5% and
structurally incomplete in 50%. During the follow-up period (median of 56 months;
5-360 months), 47.7% presented with disease progression and 17.8% experienced
disease-related death. In 53.3% of the cases at least one molecular alteration
(TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate
analysis, TERTp mutation was the factor associated with the highest risk (6
times) of having structural disease after initial therapy (p = 0.01), followed by
vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and
distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation
was associated with disease progression, and diminished disease progression-free
survival (PFS). The presence of distant metastasis, vascular invasion and gross
ETE were significantly associated with the risk of disease progression.
CONCLUSIONS: TERTp mutation appears be an indicator of both persistence and
progression of structural disease after initial therapy in aggressive variants of
TCDFC, and associates with a shorter progression free survival regardless of the
therapy employed.
PMID- 29948936
TI - Assessment of return to play in professional overhead athletes subjected to
arthroscopic repair of rotator cuff tears and associated labral injuries using
the Italian version of the Kerlan-Jobe Orthopedic Clinic Shoulder and Elbow
score.
AB - BACKGROUND: The self-administered Kerlan-Jobe Orthopedic Clinic (KJOC) Shoulder
and Elbow questionnaire is a reliable and sensitive outcome tool to assess upper
extremity athletic performance and functional changes affecting return to play in
overhead athletes. We report the results of a study of return to sport in
professional overhead athletes at a mean follow-up of 2 years after arthroscopic
repair of rotator cuff tears and associated labral injuries using the Italian
version of the score. MATERIALS AND METHODS: A total number of 38 patients
completed the 10-item questionnaire before and after surgery. They were also
asked (1) whether they had returned to play; (2) how many months after the
operation they had done so; (3) the level of postoperative performance (preinjury
or less); and (4) whether they had had to change sport due to their shoulder
problems. RESULTS: Significant differences were found (1) between preoperative
and postoperative scores; (2) between the scores of patients who returned to play
at preinjury level and those who merely returned to competition; and (3) between
the postoperative subscores of 8/10 items, which were higher in the patients who
returned to preinjury performance than in those who merely returned to play; the
two items that were not significantly different between these subgroups concerned
pain and joint stability. Even though item analysis highlighted a major role for
athletic performance in recovery of preinjury performance, it also stressed that
the athlete's relationship with coach, agent, and staff and his/her feeling of
the extent to which the arm affects current performance significantly contribute
to the final score. CONCLUSIONS: The KJOC Shoulder and Elbow score provides an
accurate and exhaustive assessment of the recovery of the athlete's shoulder in
relation to preinjury performance and provides the surgeon with key information
on the pros and cons of surgical management.
PMID- 29948937
TI - Antiresorptive drug-related osteonecrosis of the jaws, literature review and 5
years of experience.
AB - PURPOSE: Bisphosphonate drug therapy provides benefits in the case of
osteoporosis and carcinomas metastasizing to the bones, but it exposes patients
to important side effects. The aim of this study was to investigate the incidence
and the appropriate surgical treatment of bone lesions and fractures due to
antiresorptive drug-related osteonecrosis of the jaws (ARONJ). METHODS: Patients
presenting with osteonecrosis lesions of the jaw, who were referred to the
Maxillo-Facial unit of the University of L'Aquila, were considered for inclusion.
Grade of the lesion and treatment choice was recorded for each patient.
Descriptive statistics were calculated and the data were analysed with Chi
squared tests. A representative case of a fracture reduction with a supra
periostal approach is reported. RESULTS: Among the 165 patients with ARONJ
lesions, 112 were female and 53 were male. In total, 115 patients received intra
venous bisphosphonate therapy and 50 received oral bisphosphonate therapy. Five
stage 2 lesions, three stage 2 lesions and two stage 3 lesions were not a
consequence of dental procedures. Eighteen surgical bone excisions were performed
and four pathological fractures were reduced. In one case (the reported one), the
combined use of platelet-rich plasma and the supra-periostal approach leads to a
successful 1-year follow-up. CONCLUSIONS: ARONJ lesions are a type of
pathological bone disease affecting the jawbones. The pathology pathway remains a
controversial and frequently discussed topic. A surgically conservative strategy
seems to be the best way to assure a comfortable quality of life to those
patients negatively affected by this condition.
PMID- 29948938
TI - Monogenic, Polygenic, and MicroRNA Markers for Ischemic Stroke.
AB - Ischemic stroke (IS) is a leading disease with high mortality and disability, as
well as with limited therapeutic window. Biomarkers for earlier diagnosis of IS
have long been pursued. Family and twin studies confirm that genetic variations
play an important role in IS pathogenesis. Besides DNA mutations found previously
by genetic linkage analysis for monogenic IS (Mendelian inheritance), recent
studies using genome-wide associated study (GWAS) and microRNA expression
profiling have resulted in a large number of DNA and microRNA biomarkers in
polygenic IS (sporadic IS), especially in different IS subtypes and imaging
phenotypes. The present review summarizes genetic markers discovered by clinical
studies and discusses their pathogenic molecular mechanisms involved in
developmental or regenerative anomalies of blood vessel walls, neuronal
apoptosis, excitotoxic death, inflammation, neurogenesis, and angiogenesis. The
possible impact of environment on genetics is addressed as well. We also include
a perspective on further studies and clinical application of these IS biomarkers.
PMID- 29948940
TI - Rapid Intracellular Zn2+ Dysregulation via Membrane Corticosteroid Receptor
Activation Affects In Vivo CA1 LTP.
AB - Involvement of membrane mineralocorticoid (MC) and glucocorticoid (GC) receptors
in synaptic Zn2+ dynamics remains unclear. Here, we tested whether synaptic
plasticity is affected by rapid intracellular Zn2+ dysregulation via membrane MC
and GC receptor activation, in comparison with intracellular Ca2+ dysregulation.
In anesthetized rats, extracellular Zn2+ level was increased under local
perfusion of the hippocampal CA1 with 500 ng/ml corticosterone. In vivo CA1 long
term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses was
attenuated by the pre-perfusion with corticosterone prior to tetanic stimulation,
and the attenuation was canceled by co-perfusion with CaEDTA, an extracellular
Zn2+ chelator, suggesting that corticosterone-induced increase in extracellular
Zn2+ is involved in the subsequent attenuation of LTP. In rat brain slices,
corticosterone-induced increases in extracellular and intracellular Zn2+ were
blocked in the presence of spironolactone, a MC receptor antagonist that canceled
corticosterone-induced attenuation of LTP. Mifepristone, a GC receptor
antagonist, which canceled corticosterone-induced attenuation of LTP, also
blocked corticosterone-induced increase in intracellular Zn2+, but not
extracellular Zn2+. Moreover, corticosterone-induced decrease in phosphorylated
CaMKII was restored in the presence of CaEDTA or spironolactone. These results
indicate that glucocorticoid rapidly induces the increase in intracellular Zn2+,
which occurs via membrane MC and GC receptor activations, and decreases
phosphorylated CaMKII level, resulting in attenuating LTP. Membrane MC and GC
receptors induce intracellular Zn2+ dysregulation via differential mechanisms. In
contrast, glucocorticoid-induced intracellular Ca2+ dysregulation is not crucial
for affecting LTP.
PMID- 29948939
TI - Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic
Parkinson's Disease and Dementia with Lewy Bodies.
AB - Mutations in the GBA gene, encoding the lysosomal hydrolase glucocerebrosidase
(GCase), are the most common known genetic risk factor for Parkinson's disease
(PD) and dementia with Lewy bodies (DLB). The present study aims to gain more
insight into changes in lysosomal activity in different brain regions of sporadic
PD and DLB patients, screened for GBA variants. Enzymatic activities of GCase,
beta-hexosaminidase, and cathepsin D were measured in the frontal cortex,
putamen, and substantia nigra (SN) of a cohort of patients with advanced PD and
DLB as well as age-matched non-demented controls (n = 15/group) using
fluorometric assays. Decreased activity of GCase (- 21%) and of cathepsin D (-
15%) was found in the SN and frontal cortex of patients with PD and DLB compared
to controls, respectively. Population stratification was applied based on GBA
genotype, showing substantially lower GCase activity (~ - 40%) in GBA variant
carriers in all regions. GCase activity was further significantly decreased in
the SN of PD and DLB patients without GBA variants in comparison to controls
without GBA variants. Our results show decreased GCase activity in brains of PD
and DLB patients with and without GBA variants, most pronounced in the SN. The
results of our study confirm findings from previous studies, suggesting a role
for GCase in GBA-associated as well as sporadic PD and DLB.
PMID- 29948941
TI - Multifaceted Regulation of ALDH1A1 by Cdk5 in Alzheimer's Disease Pathogenesis.
AB - This study revealed multifaceted regulation of ALDH1A1 by Cdk5 in Alzheimer's
disease (AD) pathogenesis. ALDH1A1 is a multifunctional enzyme with
dehydrogenase, esterase, and anti-oxidant activities. ALDH1A1 is also a major
regulator of retinoic acid (RA) signaling, which is critical for normal brain
homeostasis. We identified ALDH1A1 as both physiological and pathological target
of Cdk5. First, under neurotoxic conditions, Cdk5-induced oxidative stress
upregulates ALDH1A1 transcription. Second, Cdk5 increases ALDH1A1 levels by
preventing its ubiquitylation via direct phosphorylation. Third, ALDH1A1
phosphorylation increases its dehydrogenase activity by altering its tetrameric
state to a highly active monomeric state. Fourth, persistent oxidative stress
triggered by deregulated Cdk5 inactivates ALDH1A1. Thus, initially, the good Cdk5
attempts to mitigate ensuing oxidative stress by upregulating ALDH1A1 via
phosphorylation and paradoxically by increasing oxidative stress. Later,
sustained oxidative stress generated by Cdk5 inhibits ALDH1A1 activity, leading
to neurotoxicity. ALDH1A1 upregulation is highly neuroprotective. In human AD
tissues, ALDH1A1 levels increase with disease severity. However, ALDH1A1 activity
was highest at mild and moderate stages, but declines significantly at severe
stage. These findings confirm that during the initial stages, neurons attempt to
upregulate and activate ALDH1A1 to protect from accruing oxidative stress-induced
damage; however, persistently deleterious conditions inactivate ALDH1A1, further
contributing to neurotoxicity. This study thus revealed two faces of Cdk5, good
and bad in neuronal function and survival, with a single substrate, ALDH1A1. The
bad Cdk5 prevails in the end, overriding the good Cdk5 act, suggesting that Cdk5
is an effective therapeutic target for AD.
PMID- 29948942
TI - Protective Effects of Curcumin Against Ischemia-Reperfusion Injury in the Nervous
System.
AB - Ischemia-reperfusion injury (I/R injury) is a common feature of ischemic stroke
which occurs when blood supply is restored after a period of ischemia. Although
stroke is an important cause of death in the world, effective therapeutic
strategies aiming at improving neurological outcomes in this disease are lacking.
Various studies have suggested the involvement of different mechanisms in the
pathogenesis of I/R injury in the nervous system. These mechanisms include
oxidative stress, platelet adhesion and aggregation, leukocyte infiltration,
complement activation, blood-brain barrier (BBB) disruption, and mitochondria
mediated mechanisms. Curcumin, an active ingredient of turmeric, can affect all
these pathways and exert neuroprotective activity culminating in the amelioration
of I/R injury in the nervous system. In this review, we discuss the protective
effects of curcumin against I/R injury in the nervous system and highlight the
studies that have linked biological functions of curcumin and I/R injury
improvement.
PMID- 29948943
TI - Perturbed Developmental Serotonin Signaling Affects Prefrontal Catecholaminergic
Innervation and Cortical Integrity.
AB - Proper development of the medial prefrontal cortex (mPFC), crucial for correct
cognitive functioning, requires projections from, among others, the serotonergic
(5-HT) and catecholaminergic systems, but it is unclear how these systems
influence each other during development. Here, we describe the parallel
development of the 5-HT and catecholaminergic prefrontal projection systems in
rat and demonstrate a close engagement of both systems in the proximity of Cajal
Retzius cells. We further show that in the absence of the 5-HT transporter (5
HTT), not only the developing 5-HT but also the catecholaminergic system,
including their projections towards the mPFC, are affected. In addition, the
layer identity of the mPFC neurons and reelin-positive interneuron number and
integration are altered in the absence of the 5-HTT. Together, our data
demonstrate a functional interplay between the developing mPFC 5-HT and
catecholaminergic systems, and call for a holistic approach in studying
neurotransmitter systems-specific developmental consequences for adult behavior,
to eventually allow the design of better treatment strategies for
neuropsychiatric disorders.
PMID- 29948944
TI - Dexamethasone Induces a Specific Form of Ramified Dysfunctional Microglia.
AB - The functional status of dynamic microglial cells plays an important role in
maintaining homeostasis of microenvironment in CNS. In a previous study, we
reported that microglia phenotype might be involved in stress vulnerability and
depression recurrence. Here, we aimed to clarify a character of microglia exposed
persistently to glucocorticoid (GC), which is representative a stress hormone, in
primary cultured microglial cells. Five nanomolars of dexamethasone (DEX, GC
agonist) for 72 h decreased CX3CR1 and CD200R expression and induced ramified
form of microglial cells in similar morphology to in vivo resident microglia.
However, the ramified form of microglia did not increase microglia signature
genes such as P2RY12, OLFML3, TMEM119, and TGFBR1. In addition, DEX-treated
microglia showed a reduction of phagocytosis function, pro-and anti-inflammatory
cytokine production, and cell proliferation. DEX washout did not restore these
changes. Based on transcriptomic analysis and functional characters of DEX
treated microglia, we performed senescence-associated beta-galactosidase (SA-beta
gal) assay in DEX-treated microglia and DEX-treated microglia showed more SA-beta
gal activity with alteration of cell cycle-related genes. Thus, our results
suggest that DEX can induce a specific phenotype of microglia (like-senescence).
PMID- 29948945
TI - Sustained CaMKII Delta Gene Expression Is Specifically Required for Long-Lasting
Memories in Mice.
AB - Although important information is available on the molecular mechanisms of long
term memory formation, little is known about the processes underlying memory
persistence in the brain. Here, we report that persistent gene expression of
CaMKIIdelta isoform participates in object recognition long-lasting memory
storage in mice hippocampus. We found that CaMKIIdelta mRNA expression was
sustained up to one week after training and paralleled memory retention.
Antisense DNA infusion in the hippocampus during consolidation or even after
consolidation impairs 7-day- but not 1-day-long memory, supporting a role of
CaMKIIdelta in memory persistence. CaMKIIdelta gene expression was accompanied by
long-lasting nucleosome occupancy changes at its promoter. This epigenetic
mechanism is described for the first time in a memory process and offers a novel
mechanism for persistent gene expression in neurons. CaMKIIdelta protein is
mainly present in nucleus and presynaptic terminals, suggesting a role in these
subcellular compartments for memory persistence. All these results point to a key
function of the sustained gene expression of this overlooked CaMKII isoform in
long-lasting memories.
PMID- 29948946
TI - Heme Oxygenase Inhibition Sensitizes Neuroblastoma Cells to Carfilzomib.
AB - Neuroblastoma (NB) is an embryonic malignancy affecting the physiological
development of adrenal medulla and paravertebral sympathetic ganglia in early
infancy. Proteasome inhibitors (PIs) (i.e., carfilzomib (CFZ)) may represent a
possible pharmacological treatment for solid tumors including NB. In the present
study, we tested the effect of a novel non-competitive inhibitor of heme
oxygenase-1 (HO-1), LS1/71, as a possible adjuvant therapy for the efficacy of
CFZ in neuroblastoma cells. Our results showed that CFZ increased both HO-1 gene
expression (about 18-fold) and HO activity (about 8-fold), following activation
of the ER stress pathway. The involvement of HO-1 in CFZ-mediated cytotoxicity
was further confirmed by the protective effect of pharmacological induction of HO
1, significantly attenuating cytotoxicity. In addition, HO-1 selective inhibition
by a specific siRNA increased the cytotoxic effect following CFZ treatment in NB
whereas SnMP, a competitive pharmacological inhibitor of HO, showed no changes in
cytotoxicity. Our data suggest that treatment with CFZ produces ER stress in NB
without activation of CHOP-mediated apoptosis, whereas co-treatment with CFZ and
LS1/71 led to apoptosis activation and CHOP expression induction. In conclusion,
our study showed that treatment with the non-competitive inhibitor of HO-1, LS1 /
71, increased cytotoxicity mediated by CFZ, triggering apoptosis following ER
stress activation. These results suggest that PIs may represent a possible
pharmacological treatment for solid tumors and that HO-1 inhibition may represent
a possible strategy to overcome chemoresistance and increase the efficacy of
chemotherapic regimens.
PMID- 29948947
TI - GABA-B1 Receptor-Null Schwann Cells Exhibit Compromised In Vitro Myelination.
AB - GABA-B receptors are important for Schwann cell (SC) commitment to a non
myelinating phenotype during development. However, the P0-GABA-B1fl/fl
conditional knockout mice, lacking the GABA-B1 receptor specifically in SCs, also
presented axon modifications, suggesting SC non-autonomous effects through the
neuronal compartment. In this in vitro study, we evaluated whether the specific
deletion of the GABA-B1 receptor in SCs may induce autonomous or non-autonomous
cross-changes in sensory dorsal root ganglia (DRG) neurons. To this end, we
performed an in vitro biomolecular and transcriptomic analysis of SC and DRG
neuron primary cultures from P0-GABA-B1fl/fl mice. We found that cells from
conditional P0-GABA-B1fl/fl mice exhibited proliferative, migratory and
myelinating alterations. Moreover, we found transcriptomic changes in novel
molecules that are involved in peripheral neuron-SC interaction.
PMID- 29948948
TI - Proteolytic Degradation of Hippocampal STEP61 in LTP and Learning.
AB - Striatal-enriched protein tyrosine phosphatase (STEP) modulates key signaling
molecules involved in synaptic plasticity and neuronal function. It is postulated
that STEP opposes the development of long-term potentiation (LTP) and that it
exerts a restraint on long-term memory (LTM). Here, we examined whether STEP61
levels are regulated during hippocampal LTP and after training in hippocampal
dependent tasks. We found that after inducing LTP by high frequency stimulation
or theta-burst stimulation STEP61 levels were significantly reduced, with a
concomitant increase of STEP33 levels, a product of calpain cleavage.
Importantly, inhibition of STEP with TC-2153 improved LTP in hippocampal slices.
Moreover, we observed that after training in the passive avoidance and the T-maze
spontaneous alternation task, hippocampal STEP61 levels were significantly
reduced, but STEP33 levels were unchanged. Yet, hippocampal BDNF content and TrkB
levels were increased in trained mice, and it is known that BDNF promotes STEP
degradation through the proteasome. Accordingly, hippocampal pTrkBTyr816,
pPLCgammaTyr783, and protein ubiquitination levels were increased in T-SAT
trained mice. Remarkably, injection of the TrkB antagonist ANA-12 (2 mg/Kg, but
not 0.5 mg/Kg) elicited LTM deficits and promoted STEP61 accumulation in the
hippocampus. Also, STEP knockout mice outperformed wild-type animals in an age-
and test-dependent manner. Summarizing, STEP61 undergoes proteolytic degradation
in conditions leading to synaptic strengthening and memory formation, thus
highlighting its role as a molecular constrain, which is removed to enable the
activation of pathways important for plasticity processes.
PMID- 29948949
TI - Sneaky Entry of IFNgamma Through Arsenic-Induced Leaky Blood-Brain Barrier
Reduces CD200 Expression by Microglial pro-Inflammatory Cytokine.
AB - Recent studies showed that neuronal surface protein CD200 plays a key role in the
regulation of neuroinflammation. Previously, we showed that arsenic (0.38 mg/kg
body weight) exposure induces microglial activation and consequently IL-6/TNF
alpha secretion. This result indicated the possibility of alteration in the
expression of CD200. Therefore, the present study was focused on checking arsenic
induced alteration in CD200 expression and revealing the underlying mechanism.
Male BALB/c mice were exposed to arsenic (vehicle, 0.038 and 0.38 mg/kg body
weight) for 60 days, and the expression level of CD200 was found to be decreased
which was rescued by minocycline (33 mg/kg body weight) co-administration. Higher
CD68 staining, increased level of IL-6/TNF-alpha, as well as higher level of
IFNgamma, were observed in in vivo arsenic-exposed groups. Interestingly, in
vitro arsenic exposure could not increase IL-6/TNF-alpha level in the culture
supernatant, whereas, supplementation of IFNgamma could mimic the in vivo
results. However, arsenic could not induce IFNgamma production from brain
endothelial cells, microglia, and astrocytes, thereby suggesting the entry of
IFNgamma through the impaired blood-brain barrier. Evans blue fluorescence in the
brain confirms altered blood-brain barrier permeability although no changes were
observed in the expression level of tight junction proteins (claudin-5 and
occludin). Finally, intracerebral injection of anti-IFNgamma neutralizing
antibody in arsenic-exposed brain reduced microglia activation (IL-6 and TNF
alpha and CD68 expression) and subsequently rescued CD200 level. Taken together,
the study showed that arsenic-mediated compromised blood-brain barrier is a major
driving force to induce microglial IL-6 and TNF-alpha production through serum
IFNgamma leading to CD200 downregulation.
PMID- 29948950
TI - Resveratrol Induces Brain Resilience Against Alzheimer Neurodegeneration Through
Proteostasis Enhancement.
AB - Resveratrol is a natural compound that mimics the antioxidant and antiaging
effects of caloric restriction, mainly mediated through SIRT1, a deacetylase that
induces longevity and neuroprotection. We aimed to analyze the effects of
resveratrol on the brain status of control non-transgenic (NoTg) and AD
transgenic (3xTg-AD) mice to discern the mechanisms involved in a potential
inducement of resilience against age-related neurodegeneration and Alzheimer's
disease (AD). Mice were fed with a diet supplemented with 100 mg/kg of
resveratrol from 2 months of age during 10 months. Resveratrol administration
induced complete protection against memory loss and brain pathology in 3xTg-AD
mice, and also induced cognitive enhancement in healthy NoTg mice. Resveratrol
improved exploration and reduced anxiety in both mouse strains, indicative of
well-being. Resveratrol reduced the presence of Abeta and p-tau pathology in the
hippocampus of the 3xTg-AD mouse. Proteostasis analysis showed the following in
both NoTg and 3xTg-AD mice: (i) increased levels of the amyloid-degrading enzyme
neprilysin, (ii) reduction of the amyloidogenic secretase BACE1, and (iii)
increase of proteasome protein levels and enhancement of proteasome activity.
Resveratrol also increased AMPK protein levels, then upregulating the SIRT1
pathway, as shown by the activation of PGC-1alpha and CREB in both mice,
resulting in further beneficial changes. Our data demonstrated that resveratrol
induces cognitive enhancement and neuroprotection against amyloid and tau
pathologies. Improvement of proteostasis by resveratrol, in both healthy and AD
mice, suggests that it is a mechanism of brain resilience and defense against
neurodegeneration caused by the accumulation of aberrant proteins.
PMID- 29948951
TI - Correction to: Cellular Trafficking of Amyloid Precursor Protein in
Amyloidogenesis Physiological and Pathological Significance.
AB - The original version of this article unfortunately contained mistake. The old
version of Fig. 3 was published.
PMID- 29948952
TI - GBM-Derived Wnt3a Induces M2-Like Phenotype in Microglial Cells Through Wnt/beta
Catenin Signaling.
AB - Glioblastoma is an extremely aggressive and deadly brain tumor known for its
striking cellular heterogeneity and capability to communicate with
microenvironment components, such as microglia. Microglia-glioblastoma
interaction contributes to an increase in tumor invasiveness, and Wnt signaling
pathway is one of the main cascades related to tumor progression through changes
in cell migration and invasion. However, very little is known about the role of
canonical Wnt signaling during microglia-glioblastoma crosstalk. Here, we show
for the first time that Wnt3a is one of the factors that regulate interactions
between microglia and glioblastoma cells. Wnt3a activates the Wnt/beta-catenin
signaling of both glioblastoma and microglial cells. Glioblastoma-conditioned
medium not only induces nuclear translocation of microglial beta-catenin but also
increases microglia viability and proliferation as well as Wnt3a, cyclin-D1, and
c-myc expression. Moreover, glioblastoma-derived Wnt3a increases microglial ARG-1
and STI1 expression, followed by an upregulation of IL-10 mRNA levels, and a
decrease in IL1beta gene expression. The presence of Wnt3a in microglia
glioblastoma co-cultures increases the formation of membrane nanotubes
accompanied by changes in migration capability. In vivo, tumors formed from Wnt3a
stimulated glioblastoma cells presented greater microglial infiltration and more
aggressive characteristics such as growth rate than untreated tumors. Thus, we
propose that Wnt3a belongs to the arsenal of factors capable of stimulating the
induction of M2-like phenotype on microglial cells, which contributes to the poor
prognostic of glioblastoma, reinforcing that Wnt/beta-catenin pathway can be a
potential therapeutic target to attenuate glioblastoma progression.
PMID- 29948953
TI - Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are
Associated with REST Inactivation.
AB - Chronic metabolic alterations may represent a risk factor for the development of
cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and
obesity are known to imprint epigenetic markers that compromise the proper
expression of cell survival genes. Here, we showed that chronic hyperglycemia (60
days) induced by a single intraperitoneal injection of streptozotocin compromised
cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in
rats. The mechanisms appear to be linked to reduced active DNA demethylation and
diminished expression of the neuroprotective transcription factor REST. The
impact of the relationship between adiposity and DNA hypermethylation on REST
expression was also demonstrated in peripheral blood mononuclear cells in obese
children with reduced levels of blood ascorbate. The reversible nature of
epigenetic modifications and the cognitive impairment reported in obese children,
adolescents, and adults suggest that the correction of the anthropometry and the
peripheral metabolic alterations would protect brain homeostasis and reduce the
risk of developing neurodegenerative diseases.
PMID- 29948955
TI - Correction to: Dysplastic features seen in a patient with acute myeloid leukemia
harboring the KMT2A-TET1 fusion gene.
AB - In the original publication of the article, the title was incorrectly published
as "Dysplastic features seen in a patient with acute myeloid leukemia harboring
the KTM2A-TET1 fusion gene". The correct title should be "Dysplastic features
seen in a patient with acute myeloid leukemia harboring the KMT2A-TET1 fusion
gene".
PMID- 29948954
TI - Two-Stage Revision Arthroplasty for the Treatment of Prosthetic Joint Infection.
AB - PURPOSE OF REVIEW: To review the diagnosis and treatment of prosthetic joint
infection (PJI) with a focus on two-stage revision arthroplasty. The text will
discuss different spacer constructs in total knee and total hip arthroplasty and
will present clinical outcome data for these various options. RECENT FINDINGS:
There is no appreciable difference in infection eradication between mobile and
static antibiotic spacers. Mobile spacers have shown improved knee range of
motion after second-stage re-implantation. Two-stage revision arthroplasty is the
gold standard treatment for PJI. The first stage involves removal of all
components, cement, and compromised soft tissues with placement of an antibiotic
impregnated spacer. Spacer options include both mobile and static spacers. Mobile
spacers offer maintenance of ambulation and joint range of motion between staged
procedures and have shown to be as effective in eradicating infection as static
spacers.
PMID- 29948956
TI - A randomized phase II study evaluating pyridoxine for the prevention of hand-foot
syndrome associated with capecitabine therapy for advanced or metastatic breast
cancer.
AB - BACKGROUND: Pyridoxine, an activated form of vitamin B6 used to treat allergic
dermatitis, may prevent capecitabine-associated hand-foot syndrome (HFS),
although evidence of the benefit of prophylactic pyridoxine is lacking. The aim
of this open-label, multicenter, randomized phase II study was to determine
whether prophylactic pyridoxine could delay the onset of capecitabine-induced HFS
in patients with advanced or metastatic breast cancer. METHODS: Patients received
either concomitant pyridoxine (60 mg per day; pyridoxine group), or no pyridoxine
but treatment with capecitabine-containing regimens (no pyridoxine group). Study
treatment was administered until the development of grade 2 or worse HFS or
disease progression. The primary endpoint was the time to onset of grade 2 or
worse HFS from the start of protocol treatment. RESULTS: A total of 135 patients
were randomized to the pyridoxine (n = 67) or no pyridoxine (n = 68) groups.
Grade 2 or worse HFS developed in 19 of 66 patients (28.8%) versus 21 of 67
patients (31.3%) in the pyridoxine and no pyridoxine groups, respectively. The
median time to onset of grade 2 or worse HFS was 13.6 and 10.6 months in the
pyridoxine and no pyridoxine groups, respectively [hazard ratio = 0.75 (80%
confidence interval 0.50-1.13), one-sided P = 0.18]. CONCLUSIONS: Prophylactic
pyridoxine was not shown to have an effect on the onset of capecitabine
associated HFS in this study.
PMID- 29948957
TI - The efficacy and feasibility of dose-dense sequential chemotherapy for Japanese
patients with breast cancer.
AB - BACKGROUND: Perioperative dose-dense chemotherapy (DDCT) with granulocyte-colony
stimulating factor (G-CSF) prophylaxis is a standard treatment for patients with
high-risk breast cancer. The approval of this approach in Japan led to the
widespread adoption of DDCT, despite limited efficacy and safety data among
Japanese patients. We evaluated the efficacy and safety of neoadjuvant DDCT for
Japanese patients with breast cancer. METHODS: This prospective, multicenter,
phase II study evaluated 52 women with operable human epidermal growth factor
receptor 2-negative breast cancer and axillary lymph node metastasis. Neoadjuvant
DDCT (adriamycin plus cyclophosphamide or epirubicin plus cyclophosphamide
followed by paclitaxel) was administrated every 2 weeks with G-CSF support. The
study endpoints were the rates of pathological complete response (pCR), febrile
neutropenia, treatment completion, toxicities, and the relative dose intensity
(RDI). RESULTS: The pCR rate was 21.9% (9/41) and the triple-negative (TN)
subtype was significantly associated with a high pCR rate (triple-negative: 53.3%
vs. luminal A: 7.7% and luminal B: 0%; p = 0.003). The treatment completion rate
was 80.8% (42/52) and the average RDI was 98.9%. Most adverse events were
manageable and tolerable. Six patients (11.5%) developed febrile neutropenia.
Grade 3-4 adverse events were slightly more common among older patients (57%)
with a low protocol completion rate (>= 65 years: 42.9% vs. <65 years: 86.7%, p =
0.0062). CONCLUSION: The pCR rate for DDCT was similar to that of standard
chemotherapy, although it was remarkably effective for the TN subtype. DDCT may
be feasible for Japanese patients with breast cancer although caution is needed
for older patients.
PMID- 29948959
TI - Hair and Scalp Changes in Cutaneous and Systemic Lupus Erythematosus.
AB - Cutaneous and systemic lupus erythematosus (SLE) commonly involves the hair and
scalp. Alopecia can result from direct activity of disease on the scalp or from
the state of physical stress in the form of telogen effluvium. Discoid lupus
erythematosus and lupus panniculitis/profundus are known to cause scarring
alopecia, while accumulation of recent studies has shown that non-scarring
alopecia in SLE may have different subtypes, comprising lupus erythematosus
specific and lupus erythematosus-nonspecific changes on histology. This review
aims to summarize the clinical pattern, trichoscopic, histopathological, and
direct immunofluorescence features of different types of alopecia in cutaneous
and systemic lupus erythematosus, as well as exploring their relationship with
SLE disease activity.
PMID- 29948958
TI - Breast cancer stem cells characterized by CD70 expression preferentially
metastasize to the lungs.
AB - BACKGROUND: Cancer stem cells (CSCs) are believed to form metastases. We sought
to determine whether CD70 + subpopulation in human breast cancers represents the
CSCs accounting for distant metastasis. METHODS: We measured the expression
levels of CD70 in breast cancer cell lines and 122 primary breast cancer samples.
We characterized the functional roles of CD70 + subpopulation in distant
metastasis of breast cancers. RESULTS: We observed a distinct pattern of CD70
expression in a panel of primary breast carcinoma samples, indicating that CD70
serves as a biomarker of lung-specific metastasis. CD70- and CD70+ cell
populations isolated from breast cancer cell lines exhibited epithelial and
mesenchymal phenotypes, respectively. CD70+ cells, but not CD70- cells, possessed
self-renewal and differentiation potentials. Tumorsphere formation in suspension
cultures and in vivo tumorigenicity were significantly greater in CD70+ cells
than in CD70- cells. Furthermore, the development of lung metastases induced by
orthotopic injection was markedly increased in mice inoculated with CD70 + cells.
CD70 contributed to the promotion of lung metastases by enhancing self-renewal
potential of CD70 + cells. CONCLUSIONS: We isolated CSCs from primary human
breast cancers and found that CD70 + subpopulations mediate lung-specific
metastasis. These findings might be used to aid in selection of patients for
postoperative adjuvant therapy.
PMID- 29948960
TI - Systems thinking and ethics in public health: a necessary and mutually beneficial
partnership.
AB - Systems thinking has emerged as a means of conceptualizing and addressing complex
public health problems, thereby challenging more commonplace understanding of
problems and corresponding solutions as straightforward explanations of cause and
effect. Systems thinking tries to address the complexity of problems through
qualitative and quantitative modeling based on a variety of systems theories,
each with their own assumptions and, more importantly, implicit and unexamined
values. To date, however, there has been little engagement between systems
scientists and those working in bioethics and public health ethics. The goal of
this paper is to begin to consider what it might mean to combine systems thinking
with public health ethics to solve public health challenges. We argue that there
is a role for ethics in systems thinking in public health as a means of
elucidating implicit assumptions and facilitating ethics debate and dialogue with
key stakeholders.
PMID- 29948961
TI - Video or In-Clinic Consultation? Selection of Attributes as Preparation for a
Discrete Choice Experiment Among Key Stakeholders.
AB - INTRODUCTION: Video consultations (VCs) provide increased accessibility of
primary care to remote areas and overall improved care for chronic patients. They
also contribute to higher patient satisfaction and improved resource management.
Despite these benefits, VC integration into the health system is complex and
slow. Understanding the VC-related preferences of three key stakeholders
patients, primary care physicians (PCPs) and policy makers (PMs)-is crucial for
achieving optimal implementation. OBJECTIVE: The aim of this study was to select
relevant attributes and levels for a discrete choice experiment (DCE) of
stakeholders' choice-VC or traditional in-clinic consultation (I-CC) in primary
care. METHODS: Ten semi-structured focus group interviews and 24 semi-structured
individual interviews were conducted. Data analysis was performed inductively,
using a thematic content analysis method. An attribute-ranking exercise was then
conducted based on the results gleaned from the interviews. RESULTS: The most
important attributes when choosing either VC or I-CC, for both patients and PMs,
were: (1) time to next available appointment; (2) time in line before
consultation; (3) relationship to PCP; and (4) quality of consultation. For PCPs,
the most important attributes were: (1) time in line before consultation; (2)
patient's self-management ability; (3) consultation purpose; (4) quality of
consultation. CONCLUSIONS: This qualitative study identified attributes and
levels for a DCE quantitative stage among three key stakeholder groups. It adds
to the literature of examples of developing DCE attributes, and to literature
about the stakeholder benefits in the area of telemedicine in healthcare.
PMID- 29948962
TI - The Parker Model: Applying a Qualitative Three-Step Approach to Optimally Utilize
Input from Stakeholders When Introducing New Device Technologies in the
Management of Chronic Rheumatic Diseases.
AB - BACKGROUND AND OBJECTIVE: Qualitative methods such as semi-structured interviews
and focus-groups are used to evaluate the applicability and relevance of device
technologies in clinical practice, but when used alone, often lack
generalizability. This study aimed to assess the face validity and feasibility of
using a composite, three-step qualitative method (the Parker Model), to inform
the development and implementation of ava(r), an electromechanical device (e
Device) for subcutaneous self-administration of the biologic, certolizumab pegol
(CZP), used to treat rheumatic diseases. METHODS: The Parker Model combines
concept mapping (CM), participatory design (PD), and stakeholder evaluation (SE).
CM, a structured group process, was used to identify patients' opinions and
concerns regarding the e-Device. Patients used this information in iterative PD
sessions to create personal e-Device prototypes in cooperation with a designer
and a healthcare professional. SE was performed based on semi-structured group
and individual interviews with patients and disease-management stakeholders.
RESULTS: The study recruited 14 patients, two doctors, two nurses, one medical
secretary, and four other public servants. Three CM workshops revealed four key
considerations: technical usability, physical design, concerns, and enthusiasm.
Four personalized prototypes were developed during PD sessions. SE confirmed that
the identified considerations were pivotal for the implementation and adaptation
of the e-Device. CONCLUSIONS: This study is the first to apply a composite,
qualitative research model when introducing an e-Device for the treatment and
management of rheumatic disease. Results show that input from patients and other
stakeholders using the Parker Model can add value to the development and
implementation of an e-Device.
PMID- 29948964
TI - Economic Evaluation for USA of Systemic Chemotherapies as First-Line Treatment of
Metastatic Pancreatic Cancer.
AB - BACKGROUND: Treatments for metastatic pancreatic cancer include monotherapy with
gemcitabine (GEM); combinations of GEM with oxaliplatin (OX + GEM), cisplatin
(CIS + GEM), capecitabine (CAP + GEM), or nab-paclitaxel (NAB-P + GEM); and the
non-GEM combination FOLFIRINOX. Combination therapies have yielded better
survival outcomes than GEM alone. A sponsor-independent economic evaluation of
these regimens has not been conducted for USA. OBJECTIVE: The objective of this
study was to estimate the cost utility and cost effectiveness of these regimens
from the payer perspective for USA. METHODS: A three-state Markov model
(progression-free, progressed disease, death) simulating the total costs and
health outcomes (quality-adjusted life-years; life-years) was developed to
estimate the incremental cost-utility and cost-effectiveness ratios. FOLFIRINOX
clinical data were obtained from trial and indirect estimates were obtained from
network meta-analyses. Lifetime horizon and 3%/year discount rates were used.
RESULTS: FOLFIRINOX was the most expensive regimen and GEM the least costly
regimen. Compared to GEM, all but one (CIS + GEM) regimen were found to be more
effective in quality-adjusted life-years and life-years. Compared to GEM, the
incremental cost-utility ratios for CAP + GEM, OX-GEM, NAB-P + GEM, and
FOLFIRINOX, were US$180,503, US$197,993, US$204,833, and US$265,718 per
additional quality-adjusted life-year, respectively; and the incremental cost
effectiveness ratios were US$88,181, US$87,620, US$135,683, and US$167,040 per
additional life-year, respectively. A probabilistic sensitivity analysis
confirmed the base-case analysis. CONCLUSIONS: This sponsor-independent economic
evaluation for USA found that OX + GEM, CAP + GEM, FOLFIRINOX, and NAB-P + GEM,
but not CIS + GEM, were more expensive but also more effective than GEM alone in
terms of quality-adjusted life-years and life-years gained. The NAB-P + GEM
regimen appears to be the most cost effective in USA at a willingness-to-pay
threshold of US$200,000/quality-adjusted life-year.
PMID- 29948963
TI - Poliovirus and Other Enteroviruses from Environmental Surveillance in Italy, 2009
2015.
AB - Within the initiatives for poliomyelitis eradication by WHO, Italy activated an
environmental surveillance (ES) in 2005. ES complements clinical Acute Flaccid
Paralysis (AFP) surveillance for possible polio cases, detects poliovirus
circulation in environmental sewage, and is used to monitor transmission in
communities. In addition to polioviruses, the analyses comprised: (i) the
monitoring of the presence of non-polio enteroviruses in sewage samples and (ii)
the temporal and geographical distribution of the detected viruses. From 2009 to
2015, 2880 sewage samples were collected from eight cities participating in the
surveillance. Overall, 1479 samples resulted positive for enteroviruses. No wild
type polioviruses were found, although four Sabin-like polioviruses were
detected. The low degree of mutation found in the genomes of these four isolates
suggests that these viruses have had a limited circulation in the population. All
non-polio enteroviruses belonged to species B and the most frequent serotype was
CV-B5, followed by CV-B4, E-11, E-6, E-7, CV-B3, and CV-B2. Variations in the
frequency of different serotypes were also observed in different seasons and/or
Italian areas. Environmental surveillance in Italy, as part of the 'WHO global
polio eradication program', is a powerful tool to augment the polio surveillance
and to investigate the silent circulation or the re-emergence of enteroviruses in
the population.
PMID- 29948966
TI - Necrotizing pneumonia caused by refractory Mycoplasma pneumonia pneumonia in
children.
AB - BACKGROUND: To investigate the clinical features of necrotizing pneumonia (NP)
caused by refractory Mycoplasma pneumoniae pneumonia (RMPP). METHODS: A
retrospective observational study was carried out in patients with NP caused by
RMPP who were admitted to our hospital from January 2008 to December 2015, and
the clinical manifestations, laboratory data, imaging performances, hospital
courses and outcomes were analyzed. RESULTS: Twenty-five patients with NP caused
by RMPP were collected, with a median age of 5.1 (4.0-7.9) years. The mean
duration of fever and hospital stay was 21.0 +/- 8.9 and 19.9 +/- 9.9 days,
respectively. The levels of lactate dehydrogenase (LDH), C-reactive protein,
interleukin (IL)-6, IL-10 and interferon-gamma were elevated. Meanwhile, the
pleural fluid cell count, LDH and protein were also increased. 80.0% of the
patients had pleural effusion; and a high incidence of lobar atelectasis and
pulmonary consolidation was found the patients. The mean duration from the onset
of symptoms to the discovery of necrotic lesions was 21.0 +/- 6.9 days. 80.0% of
the patients were administrated corticosteroids, and bronchoalveolar lavage was
extracted separately from all patients. Of the 20 patients who presented with
pleural effusion, 11 underwent thoracocentesis alone and 2 underwent chest
drainage. All patients received prolonged courses of antibiotics (32.2 +/- 8.7
days). All patients were dischaged home and recovered without surgical
intervention; and chest lesions were resolved or only minimal residual fibrotic
changes were residual within 3.0 (2.0-6.0) months. CONCLUSIONS: Necrotizing
pneumonia caused by RMPP is severe, however, self-limiting and reversible. Good
outcomes can be achieved with appropriate management.
PMID- 29948965
TI - Costs of Invasive Meningococcal Disease: A Global Systematic Review.
AB - BACKGROUND: Invasive meningococcal disease remains a public health concern
because of its rapid onset and significant risk of death and long-term
disability. New meningococcal serogroup B and combination serogroup ACWY vaccines
are being considered for publicly funded immunization programs in many countries.
Contemporary costing data associated with invasive meningococcal disease are
required to inform cost-effectiveness analyses. OBJECTIVE: The objective of this
study was to estimate costs and resource utilization associated with acute
infection and the long-term care of invasive meningococcal disease. DATA SOURCES
AND METHODS: PubMed, EMBASE, The Cochrane Library, health economic databases, and
electronically available conference abstracts were searched. Studies reporting
any costs associated with acute infection and long-term sequelae of invasive
meningococcal disease in English were included. All costs were converted into
purchasing power parity-adjusted estimates [international dollars (I$)] using the
Campbell and Cochrane Economics Methods Group and the Evidence for Policy and
Practice Information and Coordinating Centre cost converter. RESULTS: Fourteen
studies met our eligibility criteria and were included. The mean costs of acute
admission ranged from I$1629 to I$50,796, with an incremental cost of I$16,378.
The mean length of hospital stay was reported to be 6-18 days in multiple
studies. The average costs reported for readmissions ranged from I$7905 to
I$15,908. Key variables such as the presence of sequelae were associated with
higher hospitalization costs and longer inpatient stay. No studies estimated
direct non-healthcare costs and productivity loss. Ten studies reported only
unadjusted mean values without using appropriate statistical methods for
adjustment. CONCLUSIONS: Invasive meningococcal disease can result in substantial
costs to healthcare systems. However, costing data on long-term follow-up and
indirect costs used to populate health economic models are lacking.
PMID- 29948968
TI - A study of decoding human brain activities from simultaneous data of EEG and fMRI
using MVPA.
AB - Neuroscientists have investigated the functionality of the brain in detail and
achieved remarkable results but this area still need further research. Functional
magnetic resonance imaging (fMRI) is considered as the most reliable and accurate
technique to decode the human brain activity, on the other hand
electroencephalography (EEG) is a portable and low cost solution in brain
research. The purpose of this study is to find whether EEG can be used to decode
the brain activity patterns like fMRI. In fMRI, data from a very specific brain
region is enough to decode the brain activity patterns due to the quality of
data. On the other hand, EEG can measure the rapid changes in neuronal activity
patterns due to its higher temporal resolution i.e., in msec. These rapid changes
mostly occur in different brain regions. In this study, multivariate pattern
analysis (MVPA) is used both for EEG and fMRI data analysis and the information
is extracted from distributed activation patterns of the brain. The significant
information among different classes is extracted using two sample t test in both
data sets. Finally, the classification analysis is done using the support vector
machine. A fair comparison of both data sets is done using the same analysis
techniques, moreover simultaneously collected data of EEG and fMRI is used for
this comparison. The final analysis is done with the data of eight participants;
the average result of all conditions are found which is 65.7% for EEG data set
and 64.1% for fMRI data set. It concludes that EEG is capable of doing brain
decoding with the data from multiple brain regions. In other words, decoding
accuracy with EEG MVPA is as good as fMRI MVPA and is above chance level.
PMID- 29948967
TI - High incidence of maternal vitamin B12 deficiency detected by newborn screening:
first results from a study for the evaluation of 26 additional target disorders
for the German newborn screening panel.
AB - BACKGROUND: Newborn screening (NBS) in Germany currently includes 15 target
disorders. Recent diagnostic improvements suggest an extension of the screening
panel. METHODS: Since August 2016, a prospective study evaluating 26 additional
target disorders (25 metabolic disorders and vitamin B12-deficiency) in addition
to the German screening panel is performed at the Newborn Screening Center
Heidelberg. First-tier results from tandem-MS screening are complemented by
second-tier strategies for 15 of the additional target disorders. NBS results of
seven patients diagnosed symptomatically with one of the additional target
disorders by selective screening since August 2016 are retrospectively evaluated.
RESULTS: Over a 13-month period, 68,418 children participated in the study.
Second-tier analyses were performed in 5.4% of samples. Only 59 (0.1%) of study
participants had abnormal screening results for one of the additional target
disorders. Target disorders from the study panel were confirmed in 12 children: 1
3-hydroxy-3-methylglutaryl coenzyme A (CoA)-lyase deficiency, 1 citrullinemia
type I, 1 multiple acyl-CoA dehydrogenase-deficiency, 1 methylenetetrahydrofolate
reductase-deficiency, and 8 children with maternal vitamin B12-deficiency. In
addition, six of seven patients diagnosed symptomatically outside the study with
one of the target disorders would have been identified by the study strategy in
their NBS sample. CONCLUSIONS: Within 13 months, the study "Newborn Screening
2020" identified additional 12 children with treatable conditions while only
marginally increasing the recall rate by 0.1%. Maternal vitamin B12-deficiency
was the most frequent finding. Even more children could benefit from screening
for the additional target disorders by extending the NBS panel for Germany and/or
other countries.
PMID- 29948969
TI - Power density measurements to optimize AC plasma jet operation in blood
coagulation.
AB - In this paper, the plasma power density and corresponding plasma dose of a low
cost air non-thermal plasma jet (ANPJ) device are estimated at different axial
distances from the nozzle. This estimation is achieved by measuring the voltage
and current at the substrate using diagnostic techniques that can be easily made
in laboratory; thin wire and dielectric probe, respectively. This device uses a
compressed air as input gas instead of the relatively-expensive, large-sized and
heavy weighed tanks of Ar or He gases. The calculated plasma dose is found to be
very low and allows the presented device to be used in biomedical applications
(especially blood coagulation). While plasma active species and charged-particles
are found to be the most effective on blood coagulation formation, both air flow
and UV, individually, do not have any effect. Moreover, optimal conditions for
accelerating blood coagulation are studied. Results showed that, the power
density at the substrate is shown to be decreased with increasing the distance
from the nozzle. In addition, both distances from nozzle and air flow rate play
an important role in accelerating blood coagulation process. Finally, this device
is efficient, small-sized, safe enough, of low cost and, hence, has its chances
to be wide spread as a first aid and in ambulance.
PMID- 29948970
TI - Risk Analysis of Prostate Cancer Treatments in Promoting Metabolic Syndrome
Development and the Influence of Increased Metabolic Syndrome on Prostate Cancer
Therapeutic Outcome.
AB - In clinical practice, few prostate cancer (PCa) patients are associated with
metabolic syndrome (MetS), while few others acquire MetS during treatment.
Whether the treatment of PCa increases the occurrence of MetS remains to be
confirmed. This study reviewed the changes in MetS patients before and after PCa
treatment to evaluate the effects of various treatment methods on MetS. We
analyzed data of 1162 PCa patients, whether or not diagnosed with MetS, and
changes in MetS patients after PCa treatment. Data of lower urinary tract
symptoms, C-reactive protein (CRP), platelet distribution width (PDW), prostate
specific antigen (PSA), Gleason score, clinical stage, treatment methods, and
progressive incidents were evaluated using logistic regression according to MetS
diagnosis. The results showed significant differences in the prevalence of MetS
before (17.38%) and after (23.67%) PCa treatment (P < 0.001). Bad diet, living
habits, and prostate cancer treatment were considered as risk factors for MetS
(OR = 1.731, 95%CI 1.367-2.193, P < 0.001). Radical prostatectomy (RP), androgen
deprivation therapy including surgical castration and medical castration, iodine
125 seed brachytherapy (125I limited), and chemotherapy were independent risk
factors of MetS. The MetS incidence rates after treatment in ADT+125I
limited+chemotherapy compared to RP+TURP+EBRT were statistically significant at
the corresponding risk grade (all P < 0.001). After treatment, the occurrence
rates of progressive incidences were higher in MetS-PCa patients compared to non
MetS-PCa patients (all P < 0.001). So, the findings suggested that among PCa
patients, multiple factors contribute to the occurrence of MetS, and PCa
treatment is one among them. ADT+125I limited+chemotherapy may be the most
influential treatment for MetS.
PMID- 29948971
TI - The Influence of Menopausal Hormone Therapy and Potential Lifestyle Interactions
in Female Cancer Development-a Population-Based Prospective Study.
AB - The past decades have seen contradictory research results on the health benefits
and risks of menopausal hormone therapy (HT). In particular, long-term
associations with overall cancer incidence and the potential interplay with other
lifestyle factors remain undetermined. In a population-based prospective cohort,
29,152 women aged 50-64 years at entry (1993-1997) were followed through 2013 for
incidence of cancer (99% complete follow-up). Cox' proportional hazards models
were used to estimate cancer incidence according to baseline HT alone and in
combination with lifestyle factors including alcohol intake, BMI, physical
activity, diet, and smoking. Among 5484 women diagnosed with cancer, baseline HT
was associated with an overall higher risk of cancer (HR 1.28; 95%CI, 1.21-1.36)
in particular, a higher risk of breast (HR 1.77; 95%CI, 1.61-1.95), ovarian (HR
1.68; 95%CI, 1.26-2.26), and endometrial (HR 1.86; 95%CI, 1.45-2.37) cancer.
Combination with other lifestyle risk factors largely displayed additive
associations. The risk of colorectal cancer was significantly lower (HR 0.79;
95%CI, 0.66-0.95). However, in the interaction analysis, only "healthy" subgroups
of women using HT had a lower risk of colorectal cancer. With an overall higher
risk of cancer among women on HT, this study underlined the importance of
considering all female cancer risks in menopausal treatment guidelines. The
largely additive associations between HT and the investigated lifestyle factors
support the notion that high levels of hormones in itself play an important
etiological role in female reproductive cancers, whereas the possible protective
impact in colorectal cancer might be limited to women with an otherwise healthy
lifestyle.
PMID- 29948972
TI - Differential molecular markers of primary lung tumors and metastatic sites
indicate different possible treatment selections in patients with metastatic lung
adenocarcinoma.
AB - PURPOSE: Detecting different molecular markers in primary tumors and metastases
may provide therapeutic information. Here we investigated differences between
primary tumors and four metastatic sites of lung adenocarcinoma in the
biomarkers' features and discussed potential therapeutic implications. METHODS: A
total of 228 patients with metastatic lung adenocarcinoma were analyzed for EGFR,
KRAS, BRAF and PIK3CA mutations detected by xTAG liquidchip technology (xTAG
LCT), as well as ERCC1, TYMS, RRM1, TUBB3, STMN1, TOP2A and VEGFR1-3 mRNA
expression detected by branched DNA-liquidchip technology (bDNA-LCT). RESULTS:
Higher rates of low ERCC1 (35.6 vs. 20.3%, P = 0.0105), RRM1 (23.3 vs. 13.0%, P =
0.0437), STMN1 (72.2 vs. 42.8%, P = 0.0000) and high VEGFR2 (34.4 vs. 18.8%, P =
0.0078) mRNA expression were found in EGFR-mutated tumors, suggesting possible
benefit from platinum, gemcitabine, taxanes or VEGFR2 inhibitors. Primary lesions
showed low ERCC1 (31.6 vs. 18.5%, P = 0.0271), TYMS (17.6 vs. 7.6%, P = 0.0300),
TUBB3 (16.9 vs. 7.6%, P = 0.0415), STMN1 (62.1 vs. 42.9%, P = 0.0065) and high
TOP2A (48.7 vs. 33.1%, P = 0.0262) mRNA expression and higher KRAS mutations
(25.7 vs. 14.1%, P = 0.0350), suggesting platinum, taxanes, pemetrexed, anti
TOP2A agents and resistant to anti-EGFR therapies. Liver metastases showed
absence of low TYMS expression, indicating insensitivity to pemetrexed-based
regimen. Pleura metastases harbored higher rates of high VEGFR2 expression (50.0
vs. 19.1%, P = 0.0127). Lymph node metastases presented higher rates of high
VEGFR2 expression (37.5 vs. 19.1%, P = 0.0253) and EGFR mutations (59.4 vs.
34.4%, P = 0.0011), suggesting use of anti-VEGFR2 and anti-EGFR therapies.
CONCLUSION: Molecular profiling of 228 lung adenocarcinomas determined a
significant difference between biomarkers such as EGFR and KRAS subtypes at
primary and metastatic sites. Our results serve as a reference for individual
treatment based on different potential targets in metastatic lung adenocarcinoma
directed by molecular profiling.
PMID- 29948973
TI - Bloodstream infection in patients with head and neck cancer: a major challenge in
the cetuximab era.
AB - PURPOSE: To assess the impact of bloodstream infection (BSI) in patients with
head and neck cancer (HNC) in the cetuximab era. METHODS: We prospectively
analysed the epidemiology, microbiology and outcomes of 51 BSI episodes occurring
in 48 patients with HNC (2006-2017). We performed a retrospective matched-cohort
study (1:2) to determine the risk factors for BSI. Finally, we compared patients
who died with those who survived to identify risk factors for mortality. RESULTS:
The most frequent HNC localization was the oropharynx (43%), and pneumonia was
the most frequent source (25%). Gram-positive BSI occurred in 55% cases, mainly
due to Streptococcus pneumoniae (21%), and among Gram-negatives, Escherichia
coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the most frequent.
Hypoalbuminemia (OR 8.4; 95% CI, 3.5-19.9), previous chemotherapy (OR, 3.2; 95%
CI, 1.3-7.4) and cetuximab therapy (OR, 2.8; 95% CI, 1.6-6.7) were significant
risk factors for BSI. Patients with BSI had a higher overall case-fatality rate
than patients without BSI (OR, 4.4; 95% CI, 1.7-11.8). Hypoalbuminemia was an
independent risk factor for the early (7 day) and overall (30 day) case
fatalities, with ORs of 0.8 (95% CI, 0.6-0.9) and 0.8 (95% CI, 0.7-0.97),
respectively. The presence of comorbidities (OR, 7; 95% CI, 1.4-34) was also an
independent risk factor for overall case-fatality. CONCLUSIONS: BSI causes high
mortality in patients with HNC and is most often secondary to pneumonia. It
occurs mainly among patients with hypoalbuminemia who receive treatment with
cetuximab or chemotherapy. The development of BSI in patients with HNC impairs
their outcome, especially in the presence of hypoalbuminemia and comorbidities.
PMID- 29948974
TI - The absolute lymphocyte count can predict the overall survival of patients with
non-small cell lung cancer on nivolumab: a clinical study.
AB - INTRODUCTION: The neutrophil-to-lymphocyte (ANC/ALC) ratio is associated with
worse prognosis in patients with NSCLC on immunotherapies, but the role of ALC
remains unclear. The previous radiation therapy causes lymphopenia, and given
approaches of combining radiation with immunotherapies, it is critical to better
understand the impact of peripheral lymphocytes. PATIENTS AND METHODS: We
evaluated retrospectively 22 patients with advanced NSCLC treated with nivolumab
at Boston Medical Center from January 2014 to September 2016 and correlated the
peripheral blood counts with the overall survival (OS) and overall time on
treatment. We assessed the effect of the previous radiation on peripheral blood
counts and clinical outcomes. RESULTS: Baseline ALC and ANC/ALC ratios are
positively and negatively correlated, respectively, with the OS on nivolumab. The
ALC and ALC/WBC ratios at 6 weeks on treatment are positively associated with the
OS. Kaplan-Meier analysis at baseline and at 6 weeks showed significantly
increased OS in the group of patients with the highest ALC. The previous
radiation therapy was positively correlated with the ANC and negatively
correlated with the ALC/WBC ratio at 8 weeks after the initiation of nivolumab.
CONCLUSION: Our finding that ALC at baseline and at 6 weeks on treatment is
positively correlated with the OS provides an easily obtained predictive marker.
Our result that the previous radiation is associated with higher ANC and lower
ALC during treatment supports that the combination of radiation therapy with
immunotherapy should be carefully applied and potentially peripheral blood counts
can be utilized to stratify patients for this approach.
PMID- 29948975
TI - Anatomy of the coronary artery and cardiac vein in the quail ventricle: patterns
are distinct from those in mouse and human hearts.
AB - Coronary vessel development has been investigated in avian and mouse embryonic
hearts. Quail embryos are a useful tool to examine vascular development,
particularly because the QH1 antibody and transgenic quail line, Tg (tie1:H2B
eYFP), are useful to trace endothelial cells. However, there are only a few
descriptions of the quail coronary vessels. Using ink injection coronary
angiography, we examined the course of coronary vessels in the fetal quail heart.
The major coronary arteries were the right and left septal arteries, which,
respectively, branched off from the right and left coronary stems. The right
septal artery ran posteriorly (dorsally) and penetrated the ventricular free wall
to distribute to the posterior surface of the ventricles. The left septal artery
ran anteriorly (ventrally) and penetrated the ventricular free wall to distribute
to the anterior surface of the ventricles. The right and left circumflex arteries
were directed posteriorly along the atrioventricular sulci. The cardiac veins
consisted of three major tributaries: the middle, great, and anterior cardiac
veins. The middle cardiac vein ascended along the posterior interventricular
sulcus and emptied into the right atrium. The great cardiac vein ran along the
anterior interventricular sulcus, entered the space between the left atrium and
conus arteriosus and emptied into the right atrium behind the aortic bulb. The
anterior cardiac vein drained the anterior surface of the right ventricle and
connected to the anterior base of the right atrium. The course of coronary
vessels in the quail heart was basically the same as that observed in chick but
was different from those of mouse and human.
PMID- 29948976
TI - Arterial irrigation of the head and neck of the pampas deer (Ozotoceros
bezoarticus, Linnaeus 1758).
AB - The pampas deer (Ozotoceros bezoarticus) is a medium-sized deer that weighs 20-40
kg. Historically, it was a widely distributed species that occupied a wide range
of open habitats, including pastures, pampas, and Brazilian savanna. However, it
is currently considered to be a species at risk of extinction. Anatomical
descriptions of the arterial supply are very useful when working with exotic
mammals. Knowledge of the locations, the distribution pattern, and the anatomical
relationships of the arteries is required when performing any intervention. The
objective of this research was to describe the normal arterial distribution
pattern in the head and neck of this species. The divisions of the common carotid
arteries, to which branches of the vertebral arteries are attached, irrigate the
head and cranial parts of the neck. The arterial distribution pattern in the head
and neck of the pampas deer was found to be similar to that described for other
cervids and bovines but showed important differences from that for the ovine. The
pampas deer had a bicarotid trunk, in contrast to other cervids. With regard to
domestic animals, the lack of a fully developed internal carotid artery and the
marked presence of a linguofacial trunk mean that it resembles the arterial
distribution described for bovines.
PMID- 29948978
TI - The Shielding Effect of Microcrystalline Cellulose on Drug Nanocrystal Particles
During Compaction.
AB - To elucidate the compaction behavior of drug nanocrystals based composite
particles (NP) during tabletting, the compaction behavior of binary mixtures of
microcrystalline cellulose (MCC) and nanocrystal particles was investigated. The
force-displacement correlation of mixtures containing different ratios of MCC and
micronized NP was studied in order to explain the nature on densification of NP
during compaction, and the resultant compaction curves (pressure as function of
in-die thickness) were systemically analyzed to elucidate the most important
mechanisms of volume reduction for MCC and NP in different stages of compaction.
The results showed that the close compaction of individual MCC was relatively
quickly achieved, and the drug NP particles could slide into the intrinsic void
spaces between MCC microparticles. This was the reason that the particles size of
MCC used in this study was significantly larger compared to that of drug NP. This
interstitial rearrangement phenomenon of NP occurred on a typical time scale and
was strongly dependent on the speed of compaction. This migration behavior
occurred on void spaces of MCC inter-particles might be identified as an elastic
stress relaxation mechanism and be helpful to dissolution of NP. MCC can
effectively shield the NP from significant aggregation during compaction process.
PMID- 29948979
TI - Influence of Geometry on the Drug Release Profiles of Stereolithographic (SLA) 3D
Printed Tablets.
AB - Additive manufacturing (3D printing) permits the fabrication of tablets in shapes
unattainable by powder compaction, and so the effects of geometry on drug release
behavior is easily assessed. Here, tablets (printlets) comprising of paracetamol
dispersed in polyethylene glycol were printed using stereolithographic 3D
printing. A number of geometric shapes were produced (cube, disc, pyramid, sphere
and torus) with either constant surface area (SA) or constant surface area/volume
ratio (SA/V). Dissolution testing showed that printlets with constant SA/V ratio
released drug at the same rate, while those with constant SA released drug at
different rates. A series of tori with increasing SA/V ratio (from 0.5 to 2.4)
were printed, and it was found that dissolution rate increased as the SA/V ratio
increased. The data show that printlets can be fabricated in multiple shapes and
that dissolution performance can be maintained if the SA/V ratio is constant or
that dissolution performance of printlets can be fine-tuned by varying SA/V
ratio. The results suggest that 3D printing is therefore a suitable manufacturing
method for personalized dosage forms.
PMID- 29948977
TI - Biological aspects of the tongue morphology of wild-captive WWCPS rats: a
histological, histochemical and ultrastructural study.
AB - The aim of this study was to characterise the tongue in wild-type rats using
several microscopic techniques. Warsaw Wild Captive Pisula Stryjek (WWCPS) rats
belong to a lineage of wild-caught rats. The study was carried out on tongues of
15 male and 15 female WWCPS rats. Histological, histochemical and ultrastructural
studies were carried out. There were no significant differences between the male
and female WWCPS rat tongues. There was a median groove approximately 1 cm long
in the apex of the tongue that faded caudally. The intermolar prominence was
clearly marked in the distal part of the lingual body. Lingual mechanical
papillae located on the surface of the tongue formed four subtypes based on their
shape: small filiform papillae, giant filiform papillae, thin elongated filiform
papillae and wide filiform papillae. Gustatory papillae formed the second group
of papillae and were divided into bud-shaped fungiform papillae, a single vallate
papilla surrounded by an incomplete papillary groove and foliate papillae, which
were a well-formed and composed of several pairs of folds divided by longitudinal
grooves. In the posterior lingual glands (mucoserous and serous), acidic
sulphated mucin-secreting cells gave a strong AB pH 2.5 positive reaction, and a
positive reaction with the AB pH 1.0 stain for acidic carboxylated mucin. Double
AB/PAS staining showed the presence of the majority of mucous cells with
predominant of acidic mucins. Positive PAS staining showed the presence of
neutral mucin. HDI staining demonstrated a weak positive reaction within Weber's
glands of the WWCPS rat tongue.
PMID- 29948980
TI - Development of Orodispersible Films Containing Benzydamine Hydrochloride Using a
Modified Solvent Casting Method.
AB - The aim of this study was to develop benzydamine hydrochloride-loaded
orodispersible films using the modification of a solvent casting method. An
innovative approach was developed when the drying process of a small-scale
production was used based on a heated inert base for casting the film. During
this process, two types of film-forming maltodextrins for rapid drug delivery
were used. They were plasticized with two different polyols (xylitol and
sorbitol). Superdisintegrant Kollidon(r) CL-F was tested as an excipient that can
induce faster disintegration of the prepared films. The influence of the
formulation parameters (dextrose equivalent of film-forming maltodextrins, a type
of plasticizer, and the presence of superdisintegrant) on the disintegration
time, mechanical properties, and moisture content of films was statistically
evaluated using a multivariate data analysis. Orodispersible films containing
maltodextrin with lower dextrose equivalent value showed better mechanical
properties (tensile strength ranged from 886.6 +/- 30.2 to 1484.2 +/- 226.9 N cm
2), lower moisture content (0.5 +/- 0.0 to 1.2 +/- 0.2%), and shorter
disintegration time (17.6 +/- 2.9 to 27.8 +/- 2.8 s). Films plasticized with
xylitol showed shorter disintegration time (17.6 +/- 2.9 to 29.2 +/- 3.8 s) than
films containing sorbitol (23.8 +/- 2.9 to 31.7 +/- 3.9 s). With the addition of
superdisintegrant Kollidon(r) CL-F, a significant influence on disintegration
time was not observed. The modified solvent casting method shows great promise in
a small-scale laboratory production of orodispersible films, e.g., in a pharmacy
lab.
PMID- 29948981
TI - Enhancing Stability of Exenatide-Containing Pressurized Metered-Dose Inhaler Via
Reverse Microemulsion System.
AB - The dispersibility and stability issues of peptide drugs during preparation and
storage hinder the widespread adoption of pressurized metered-dose inhaler
(pMDI). This study aimed to develop a reverse microemulsion (RM) of exenatide
(EXE) pMDI through a liquid-based bottom-up method, thus to overcome the
stability issue of peptide drugs encountered in traditional top-down methods,
such as milling down and high-pressure homogenization. In this study, Pluronic(r)
L64 (L64) was chosen as a surfactant to prepare the EXE-RM pMDI formulations with
the assistance of ethanol. The results showed RM possessed a particle size of
123.80 +/- 2.91 nm with 0.121 +/- 0.024 PdI and a satisfied fine-particle
fraction of 41.30 +/- 3.73% measured by a next-generation impactor. In addition,
the dispersion stability of RM pMDI was maintained after storage at 4 degrees C
for 50 days. The secondary structure of EXE was maintained during the preparation
process. Moreover, the results indicated that L64 was compatible with cells and
could improve the penetration of EXE through cell monolayers. Through the liquid
based bottom-up method, EXE-RM pMDI was successfully prepared and exhibited
favorable stability and aerodynamic performance. This study offers a preparation
strategy to enhance the stability of peptides in pMDIs.
PMID- 29948982
TI - A Simplified Geometric Model to Predict Nasal Spray Deposition in Children and
Adults.
AB - A mathematical approach was developed to estimate spray deposition patterns in
the nasal cavity based on the geometric relationships between the emitted spray
plume and the anatomical dimensions of the nasal valve region of the nasal
cavity. Spray plumes were assumed to be spherical cones and the nasal valve
region was approximated as an ellipse. The effect of spray plume angle (15-85
degrees ) on the fraction of the spray able to pass through the nasal valve
(deposition fraction) was tested for a variety of nasal valve (ellipse) shapes
and cross-sectional areas based on measured dimensions from pediatric and adult
nasal cavities. The effect of the distances between the tip of the nasal spray
device and the nasal valve (0.2-1.9 cm) on the deposition fraction was also
tested. Simulation results show that (1) decreasing spray plume angles resulted
in higher deposition fractions, (2) deposition fraction was inversely
proportional to the spray distance and the nasal valve (ellipse) major/minor axis
ratio, and (3) for fixed major/minor axis ratios, improved deposition occurred
with larger nasal valve cross-sectional areas. For a typical adult nasal valve,
plume angles of less than 40 degrees emitted from a distance of 1 cm resulted
depositions greater than 90% within the main nasal cavity, whereas for a 12-year
old child, only the most narrow plume angles (< 20 degrees ) administered
resulted in significant deposition beyond the nasal valve.
PMID- 29948983
TI - Levobupivacaine Thermogel for Long-acting Analgesia.
AB - The adequate management of analgesia, by pharmacological methods or not, is a
great challenge. Local anesthetics are used for pain relief, mainly by
parenteral, intramuscular, catheter, and other routes of administration. The use
of in situ forming systems becomes an alternative for the control of pain. The
present research investigates development of thermogels containing poloxamer and
levobupivacaine. All formulations were prepared by the cold method; the
compatibilities of the excipients were evaluated by DSC, rheology and
viscosities, transition temperature, syringeability, release kinetics, and
permeation. The compatibility of the tested excipients with the drug was
initially observed; all formulations had a viscosity increase at 37 degrees C.
Different delivery rates were observed in both the release and permeation
studies. The developed systems maintained the in vitro release of the drug for a
long period, likely decreasing side effects in vivo and avoiding the need for
supplementary analgesia by other routes.
PMID- 29948984
TI - Gastroretentive Microsponge as a Promising Tool for Prolonging the Release of
Mitiglinide Calcium in Type-2 Diabetes Mellitus: Optimization and
Pharmacokinetics Study.
AB - Diabetes mellitus is one of the leading causes of death due to the persistent
hyperglycemia that leads to potential complications. Lack of patients' adherence
to their prescribed medication regimens, due to the requirement of frequent
dosing, leads to failure of 40-50% of patients to manage their disease. Thus,
microsponges of the novel short half-life mitiglinide calcium (MTG) were
formulated using Quasi-emulsion solvent diffusion method, employing Eudragit
RS100, ethyl cellulose, and polyvinyl alcohol, then characterized in terms of
production yield, entrapment efficiency, particle size, in vitro buoyancy, in
vitro drug release, and in vivo pharmacokinetics in rabbits. Optimization was
done using response surface methodology; the optimized formulation was
investigated by FTIR, DSC, and SEM. Results revealed that the optimized MTG
microsponge was successfully formulated with high production yield (61.61% +/-
0.6), entrapment efficiency (77.7% +/-1.37), and particle size of 192.76 MUm and
it remained buoyant over simulated gastric fluid for 24 h with high percentage of
in vitro buoyancy (91.01% +/- 2.5). Moreover, it sustained the in vitro drug
release with cumulative % release of 83.74 +/- 1.5 after 24 h. This microsponge
was highly porous in nature with interconnected pores where MTG was entrapped
with good compatibility as confirmed by SEM, DSC, and FTIR analysis;
Pharmacokinetic studies showed improvement in Cmax and AUC0-infinity (1.92- and
20.68-fold, respectively) with marked prolongation in MRT and t1/2 (7.22- and
7.97-fold, respectively) than the marketed tablet. Thus, it is a promising
approach to improve diabetic patients' compliance by eliminating the necessity of
frequent dosing thus attaining better diabetes control.
PMID- 29948985
TI - Application of FT-NIR Analysis for In-line and Real-Time Monitoring of
Pharmaceutical Hot Melt Extrusion: a Technical Note.
AB - Continuous manufacturing, a gaining interest paradigm in the pharmaceutical
industry, requires in-process monitoring of critical process parameters to ensure
product consistency. This study demonstrated the application of Fourier transform
near-infrared (FT-NIR) spectroscopy in conjunction with chemometrics modeling for
in-line hot melt extrusion process monitoring. The obtained results suggested
that inline FT-NIR analysis, along with a tailored NIR reflector, is a viable
process analytical tool to monitor active pharmaceutical ingredient concentration
as well as processing parameters.
PMID- 29948986
TI - Metformin-Loaded Hyaluronic Acid Nanostructure for Oral Delivery.
AB - The objective of this study was to develop a nanodelivery system containing a
mucoadhesive polymer hyaluronic acid (HA) for oral delivery. Metformin was used
as a model drug. Blank and drug-loaded HA nanostructures were prepared by
precipitation method and characterized for particle size (PS), zeta potential
(ZP), physical stability (over 65 days), surface morphology, moisture content,
and physical state of the drug in the nanostructures. The cytotoxicity and
hemolysis potential of the delivery system was assessed in Caco-2 cells and whole
human blood, respectively. The in vitro release of metformin and its uptake in
Caco-2 cells was evaluated using high-performance liquid chromatography. Ex vivo
permeability of metformin was measured through goat intestinal membrane. The
nanoparticles were physically stable and neutrally charged with an average PS of
114.53 +/- 12.01 nm. This nanodelivery system existed as nanofibers containing
metformin in a crystalline state. This delivery system released the drug rapidly
with > 50% of metformin released within 1 h. Cellular uptake studies on Caco-2
cells indicated higher uptake of metformin from nanoparticle as compared to
metformin in solution, up to first 45 min. Ex vivo permeability studies on the
other hand showed a higher metformin permeability from solution relative to that
from nanoparticles through the goat intestinal membrane. Metformin nanoparticles
were non-toxic at therapeutic concentrations in Caco-2 cells and showed no
hemolytic effect to RBCs. This study indicates the preparation, characterization,
as well as the potential use of HA nanostructures for oral delivery.
PMID- 29948987
TI - Development and Gamma Scintigraphy Study of Trigonella foenum-graecum (Fenugreek)
Polysaccharide-Based Colon Tablet.
AB - The major concern with the use of some synthetic excipients is their safety
towards biological tissues, hence influencing the reliability of products. With
the aim to minimize dependency on highly toxic synthetic excipients, the present
study was designed to deliver metronidazole (MNZ) into the colonic region for
localized treatment of amoebiasis using natural polysaccharide-based drug
delivery. Compression-coated tablets were prepared using water extractable
natural polysaccharide from Trigonella foenum-graecum (FG). Physical properties
of the tablets were evaluated and dissolution study was performed at pH 1.2, 6.8,
and 7.4 with rat cecal material. Results indicate that all batches demonstrated
pH-dependent drug release and prevented release into the stomach, allowing traces
into the intestine and highest availability into the colon. A significant
correlation (r2 = 0.975) was found between the coating levels of extracted
polysaccharide and lag time release of drug. Gamma scintigraphy images of in vivo
study conducted on human volunteers showed a small intestinal transit time, i.e.,
3-5 (4.2 +/- 0.4) h and confirmed that the tablets reached the colon within 6-8
h. The present study revealed that the FG polysaccharide-based double compression
tablets may be promising colon-specific drug carriers with reduced toxic effects
of commonly used synthetic excipients.
PMID- 29948988
TI - Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation.
AB - Nepafenac is a nonsteroidal anti-inflammatory drug (NSAID), currently only
available as 0.1% ophthalmic suspension (Nevanac(r)). This study utilized
hydroxypropyl-beta-cyclodextrin (HPBCD) to increase the water solubility and
trans-corneal permeation of nepafenac. The nepafenac-HPBCD complexation in the
liquid and solid states were confirmed by phase solubility, differential scanning
calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared
spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) analyses.
Nepafenac 0.1% ophthalmic solution was formulated using HPBCD (same pH and
osmolality as that of Nevanac(r)) and pig eye trans-corneal permeation was
studied versus Nevanac(r). Furthermore, nepafenac content in cornea, sclera,
iris, lens, aqueous humor, choroid, ciliary body, retina, and vitreous humor was
studied in a continuous isolated pig eye perfusion model in comparison to the
suspension and Nevanac(r). Permeation studies using porcine corneas revealed that
the solution formulation had a permeation rate 18 times higher than Nevanac(r).
Furthermore, the solution had 11 times higher corneal retention than Nevanac(r).
Drug distribution studies using porcine eyes revealed that the solution
formulation enables detectable levels in various ocular tissues while the drug
was undetectable by Nevanac(r). The ocular solution formulation had a
significantly higher drug concentration in the cornea compared to the suspension
or Nevanac(r).
PMID- 29948989
TI - Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D
Printed pH-Responsive Solid Dosage Forms.
AB - Three-dimensional printing is being steadily deployed as manufacturing technology
for the development of personalized pharmaceutical dosage forms. In the present
study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug
loaded non-coated and chitosan-coated alginate beads for the targeted colonic
delivery of 5-fluorouracil (5-FU). A mixture of Eudragit(r) L100-55 and
Eudragit(r) S100 was fabricated by means of hot-melt extrusion (HME) and the
produced filaments were printed utilizing a fused deposition modeling (FDM) 3D
printer to form the pH-responsive layer of the tablet with the rest comprising of
a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate
particles were characterized for their physicochemical properties
(thermogravimetric analysis, differential scanning calorimetry, X-ray
diffraction), their surface topography was visualized by scanning electron
microscopy and the filaments' mechanical properties were assessed by instrumented
indentation testing and tensile testing. The optimized filament formulation was
3D printed and the structural integrity of the hollow tablet in increasing pH
media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed
tomography (MUCT). In vitro release studies demonstrated controlled release of 5
FU from the alginate beads encapsulated within the hollow pH-sensitive tablet
matrix at pH values corresponding to the colonic environment (pH 7.4). The
present study highlights the potential of additive manufacturing in fabricating
controlled-release dosage forms rendering them pertinent formulations for further
in vivo evaluation.
PMID- 29948990
TI - Sustained Release of Poorly Water-Soluble Drug from Hydrophilic Polymeric Film
Sandwiched Between Hydrophobic Layers.
AB - This proof-of-concept study explores the feasibility of using a drug-loaded
hydrophilic polymeric layer sandwiched between two hydrophobic layers for
improving film drug load while achieving sustained release of poorly water
soluble drug. Such films having total thickness in range ~ 146-250 MUm were
prepared by slurry-based casting using hydrophilic hydroxypropyl methylcellulose
(HPMC) as matrix layer containing fenofibrate (FNB) as the model drug, encased
between two very thin rate-limiting layers of 10 MUm each of hydrophobic poly-E
caprolactone (PCL). Film precursor slurry consisted of HPMC with plasticizer and
water along with micronized FNB powders, which were dry-coated with hydrophilic
silica. Characterization techniques demonstrated the presence of homogeneously
dispersed crystalline FNB in films. The films are very thin and hence two
dimensional; hence, average drug load per unit area in range ~ 5 to ~ 9 mg/cm2
could be achieved by altering the thickness of the drug matrix layer. Drug amount
and drug content uniformity were measured through assay of ten circular samples ~
0.712 cm2 in area punched out using a circular-shaped punch tool. Drug release
rate was investigated using USP IV flow-through cell and surface dissolution
imaging system. Thinner films followed Fickian diffusion, and thicker films
followed non-Fickian anomalous diffusion. Overall, the application of middle
layer thickness could be used as a tool to manipulate drug load without the need
for altering its formulation or precursor preparation by changing its thickness,
hence achieving relatively high drug loading yet having sustained release of
drug.
PMID- 29948991
TI - Clinical predictors and gender-wise variations in dyssynergic defecation
disorders.
AB - BACKGROUND: There is insufficient data from India regarding clinical predictors
of dyssynergic defecation. AIM: To identify demography, symptom, and colonoscopic
parameters that can predict dyssynergic defecation (DD) among patients with
chronic constipation (CC) and to compare the profile among male and female
patients with DD. METHODS: Data collected from three centers during June 2014 to
May 2017 included age, gender, symptom duration, form and consistency of stools,
digital examination, colonoscopy, and anorectal manometry (ARM). Patients were
grouped based on ARM diagnosis: group I (normal study) and group II (DD). The two
groups were compared for demography, symptom profile, and colonoscopy findings.
Gender-wise subset analysis was done for those with the normal and abnormal ARM
using chi-square and unpaired t tests. RESULTS: Of 236 patients with CC
evaluated, 130 (55%) had normal ARM and 106 (45%) had DD. Male sex, straining
during defecation, bleeding per rectum, and abnormal colonoscopic diagnosis were
significantly more common in group II. While bleeding per rectum and absence of
urge to defecate were more common in males (p < 0.02), straining, digital
evacuation, and hard stools were commoner in females with DD. CONCLUSION:
Straining during defecation, bleeding per rectum, and abnormal colonoscopy
findings were more common in patients with DD. Symptoms of bleeding per rectum
and absence of urge to defecate in men and straining during defecation in female
patients were significantly associated with DD. Symptoms differ in males and
females with DD.
PMID- 29948992
TI - Is the emergence of inflammatory bowel disease a prime example of "the third
epidemiological transition"?
PMID- 29948993
TI - Prevalence of celiac disease among pediatric patients with cryptogenic cirrhosis
and effect of gluten-free-diet.
AB - BACKGROUND: Liver involvement in celiac disease (CD) is classified into
autoimmune and cryptogenic. The association between CD and autoimmune liver
diseases like autoimmune hepatitis, primary biliary cirrhosis, and primary
sclerosing cholangitis is well-established; however, the data on patients with
cryptogenic cirrhosis, particularly from India, are scanty. So we did this study
to find the prevalence of CD in patients with cryptogenic cirrhosis. METHODS:
This was a prospective observational study, involving children of less than 18
years old attending Pediatric and Gastroenterology clinic with a diagnosis of
cryptogenic cirrhosis. The patients were evaluated for CD and divided into two
groups: chronic liver disease (CLD) with CD, and CLD without CD. Both the groups
were followed up for 6 months. CLD with CD group was treated with gluten-free
diet (GFD) and CLD without CD group was followed up without any specific
intervention except standard care of CLD. RESULTS: Out of 84 patients, 11 (13.1%)
were diagnosed as CLD with CD. There was an improvement in hemoglobin levels,
liver function tests, and Child-Pugh score after initiation of GFD in CLD with CD
group. CONCLUSION: The prevalence of CD in cryptogenic cirrhosis was 13.1%.
Screening for CD is recommended for cryptogenic cirrhosis. Hepatic functions
improve with a GFD in CD patients with cirrhosis.
PMID- 29948995
TI - Predicting Promiscuous T Cell Epitopes for Designing a Vaccine Against
Streptococcus pyogenes.
AB - One of the most dangerous human pathogens with high prevalence worldwide is
Streptococcus pyogenes, which has major impacts on global morbidity and
mortality. A major challenge for S. pyogenes vaccine development is the detection
of epitopes that confer protection from infection by multiple S. pyogenes types.
Our aim was to identify the most conserved and immunogenic antigens of S.
pyogenes, which can be a potential candidate for vaccine design in the future.
Eight important surface proteins were analyzed. Using different prediction
servers, strongest epitopes were selected. They had the ability to stimulate the
humoral and cell-mediated immune system. Molecular docking was performed for
measuring free-binding energy of selected epitopes. Seven epitopes from three
surface proteins were selected as potential candidates for vaccine development.
Conservation of selected epitopes among different Streptococcus types was
checked. Further in vitro and in vivo tests are required to validate the
suitability of the epitopes for vaccine design.
PMID- 29948994
TI - Comparative study of tinidazole versus metronidazole in treatment of amebic liver
abscess: A randomized control trial.
AB - BACKGROUND: Metronidazole is a drug of choice for amebic liver abscess (ALA), but
has long course and significant side effects. Thus, drugs like tinidazole with a
better tolerability record need evaluation. METHODS: We conducted a randomized
controlled trial at the Department of Gastroenterology, SMS Hospital, Jaipur,
India. One hundred and fifty admitted patients were randomized into two treatment
groups, metronidazole (group M, n = 75) and tinidazole (group T, n = 75).
Patients were observed for clinical response, laboratory parameters, imaging, and
side effects. Early clinical response (ECR) was defined as the absence of fever
and abdominal pain within 72 h of treatment. Symptomatic clinical response (SCR)
was defined as the absence of fever and abdominal pain irrespective of duration
of treatment required. Follow up was done at 1, 3, and 6 months. RESULTS: ECR was
62.3% in group T vs. 37.7% in group M (p = 0.02). SCR was shorter in group T than
group M (3.29 +/- 1.61 days vs. 5.67 +/- 2.93, p <= 0.001). Mean residual volume
at the end of 1 month was lower in group T (130.7 +/- 108.1 vs. 184.7 +/- 143.3
mL, p = 0.01) and no significant difference was seen at 3 and 6 months.
Tinidazole was better tolerated with fewer side effects. Low socioeconomic
status, baseline abscess volume > 500 mL, hypoalbuminemia, pleural effusion, and
history of ethanol use were associated with a late clinical response on
univariate analysis of which low socioeconomic status was the only associated
factor. CONCLUSION: Tinidazole, as compared to metronidazole, has early clinical
response, shorter treatment course, favorable rate of recovery, and high
tolerability; thus, tinidazole can be preferred over metronidazole in ALA.
PMID- 29948996
TI - Using Natural Waste Material as a Matrix for the Immobilization of Enzymes:
Chicken Eggshell Membrane Powder for beta-Galactosidase Immobilization.
AB - Avian eggshell membranes are good candidates as a matrix for immobilization
procedures. Chicken eggshell, a waste material available from the poultry
industry as a byproduct, is a very safe and cheap raw material. While pieces of
eggshell membrane, or even particles from whole eggshell, have been previously
used for these purposes, we report here the use of eggshell membrane powder for
E. coli beta-galactosidase immobilization with glutaraldehyde as cross-linker. A
kinetic characterization is provided for eggshell membrane powder-bound enzyme
compared to free enzyme. Results show a remarkable similarity between bound and
free enzyme and also that the immobilized enzyme is stable and can be reused
several times. Moreover, bound enzyme is able to produce glucose from skim milk
serum.
PMID- 29948997
TI - Practical Pearl: Use of MRI to Differentiate Pseudo-subarachnoid Hemorrhage from
True Subarachnoid Hemorrhage.
PMID- 29948999
TI - Successful Wean Despite Emergence of Ictal-Interictal EEG Patterns During the
Weaning of Prolonged Burst-Suppression Therapy for Super-Refractory Status
Epilepticus.
AB - BACKGROUND: Management of refractory status epilepticus (SE) commonly involves
the induction of burst suppression using intravenous anesthetic agents. However,
the endpoints of these therapies are not well defined. Weaning anesthetic agents
are complicated by the emergence of electroencephalogram (EEG) patterns along the
ictal-interictal continuum (IIC), which have uncertain significance given that
IIC patterns may worsen cerebral metabolism and oxygenation, have a dissociation
between scalp and depth EEG recordings, or may indicate a late stage of SE
itself. Determining the significance of IIC patterns in the unique context of
anesthetic weaning is important to prevent the potential for unnecessarily
prolonging anesthetic coma. METHODS: Among 118 individuals with SE, we
retrospectively identified a series of patients who underwent at least 24 h of
burst-suppression therapy, experienced two or more weaning trials, and developed
IIC patterns during anesthetic weaning. Anesthetic titration strategies during
the emergence of these patterns were examined. RESULTS: Each of the six
individuals who met inclusion criteria experienced aggressive weaning despite the
emergence of IIC patterns. The IIC patterns that were encountered during
anesthetic weaning (including generalized and lateralized periodic discharges)
are described in detail. Favorable outcomes were reported in each subject.
CONCLUSION: IIC patterns encountered during anesthetic weaning may be
transitional and warrant observation, allowing for the emergence of more
definitive clinical or electrographic results. The metabolic impact of these IIC
patterns on brain activity is uncertain, but weaning strategies that treat IIC as
a surrogate of recurrent SE risk further prolonging anesthetic management and its
known toxicity. We speculate that these patterns may have a context-specific
association with SE relapse, with less-risk conferred when these patterns are
observed during the weaning of anesthetic agents after prolonged burst
suppression therapy. Other electrographic features aside from this clinical
context may discriminate the risk of SE relapse, such as EEG background activity.
PMID- 29948998
TI - Noninvasive Intracranial Pressure Assessment in Acute Liver Failure.
AB - BACKGROUND: Elevated intracranial pressure (ICP) is an important cause of death
following acute liver failure (ALF). While invasive ICP monitoring (IICPM) is
most accurate, the presence of coagulopathy increases bleeding risk in ALF. Our
objective was to evaluate the accuracy of three noninvasive ultrasound-based
measures for the detection of concurrent ICP elevation in ALF-optic nerve sheath
diameter (ONSD) using optic nerve ultrasound (ONUS); middle cerebral artery
pulsatility index (PI) on transcranial Doppler (TCD); and ICP calculated from TCD
flow velocities (ICPtcd) using the estimated cerebral perfusion pressure (CPPe)
technique. METHODS: In this retrospective study, consecutive ALF patients
admitted over a 6-year period who underwent IICPM as well as measurement of ONSD,
TCD-PI or ICPtcd were included. ONSD was measured offline by a blinded
investigator from deidentified videos. The ability of highest ONSD, TCD-PI, and
ICPtcd to detect concurrent invasive ICP > 20 mmHg was assessed using receiver
operating characteristic (ROC) curves. The ROC area under the curve (AUC) was
calculated with 95% confidence interval (95% CI) and evaluated against the null
hypothesis of AUC = 0.5. Noninvasive measures were also evaluated as predictors
of in-hospital death. RESULTS: Forty-one ALF patients were admitted during the
study period. In total, 27 (66%) underwent IICPM, of these, 23 underwent ONUS and
21 underwent TCD. Eleven out of 23 (48%) patients died (two from intracranial
hypertension). Results of ROC analysis for detection of concurrent ICP > 20 mmHg
were as follows: ONSD AUC = 0.59 (95% CI 0.37-0.79, p = 0.54); TCD-PI AUC = 0.55
(95% CI 0.34-0.75, p = 0.70); and ICPtcd AUC = 0.90 (0.72-0.98, p < 0.0001). None
of the noninvasive measures were significant predictors of death. CONCLUSIONS: In
patients with ALF, neither ONSD nor TCD-PI reliably detected concurrent ICP
elevation on invasive monitoring. Estimation of ICP (ICPtcd) using the TCD CPPe
technique was associated with concurrent ICP elevation. Additional studies of TCD
CPPe in larger numbers of ALF patients may prove worthwhile.
PMID- 29949000
TI - Clinical Correlates of Periodic Discharges and Nonconvulsive Seizures in
Posterior Reversible Encephalopathy Syndrome (PRES).
AB - IMPORTANCE: The pathophysiological mechanisms of Posterior Reversible
Encephalopathy Syndrome (PRES) and related seizures remain poorly understood. The
prevalence and clinical significance of nonconvulsive seizures (NCSz) and related
epileptiform patterns during continuous electroencephalography monitoring (CEEG)
in PRES have not been well described. OBJECTIVE: To report the prevalence,
characteristics and risk factors for NCSz and related highly epileptiform
patterns in patients with PRES, and to determine their relation to imaging
abnormalities and outcome. DESIGN, SETTING AND PARTICIPANTS: From a prospective
CEEG database, we retrospectively identified patients with PRES and reviewed
their medical charts. Based on CEEG findings, we designed a retrospective cohort
study comparing two groups defined based on the presence or the absence of NCSz
and/or periodic discharges (PDs). MAIN OUTCOMES AND MEASURES: The prevalence and
risk factors for PDs and NCSz, description of EEG and magnetic resonance imaging
(MRI) abnormalities and functional outcome as measured by the Glasgow Outcome
Scale (GOS) at hospital discharge. RESULTS: Among 37 eligible patients, 23 (62%)
had PDs or NCSz. The presence of NCSz was associated with the presence of PDs
(15/22 vs. 1/15; p = 0.0002). NCSz and PDs were usually either lateralized or
bilateral independent and predominated in the posterior regions. No clinical
features were associated with the occurrence of PDs or NCSz. Cortical restricted
diffusion on MRI was more frequent in the PDs/NCSz group (17/23 vs. 1/14; p <
0.001). PDs/NCSz were associated with worse outcome, with 3 deaths vs. 0 in the
no PDs/NCSz group and fewer cases with low disability (4 vs. 9 cases with GOS =
5, p < 0.04). CONCLUSIONS AND RELEVANCE: Our results reveal a high prevalence of
NCSz and PDs in critically ill patients with PRES and an association with
restricted diffusion and worse outcome, whether treating or preventing these EEG
findings can improve outcome requires further research.
PMID- 29949001
TI - Safety and Reliability of Bedside, Single Burr Hole Technique for Intracranial
Multimodality Monitoring in Severe Traumatic Brain Injury.
AB - BACKGROUND: We aimed to provide a systematic description of our 2-year experience
using a standardized bedside, single burr hole approach to intracranial
multimodality monitoring (MMM) in patients with severe traumatic brain injury
(sTBI), focusing on safety and probe reliability. METHODS: We performed this
observational cohort study at a university-affiliated, Level I trauma center with
dedicated 20-bed neuroscience intensive care unit. We included 43 consecutive
sTBI patients who required MMM to guide clinical care based on institutional
protocol and had a four-lumen bolt placed to measure intracranial pressure, brain
tissue oxygen, regional cerebral blood flow, brain temperature, and intracranial
electroencephalography. RESULTS: sTBI patients were aged 41.6 +/- 17.5 years
(mean +/- SD) and 84% were men. MMM devices were placed at a median of 12.5 h
(interquartile range [IQR] 9.0-21.4 h) after injury and in non-dominant frontal
lobe in 72.1% of cases. Monitoring was conducted for a median of 97.1 h (IQR 46.9
124.6 h) per patient. While minor hemorrhage, pneumocephalus, or small bone chips
were common, only one (2.4%) patient experienced significant hemorrhage related
to device placement. Radiographically, device malpositioning was noted in 13.9%
of patients. Inadvertent device discontinuation occurred for at least one device
in 58% of patients and was significantly associated with the frequency of travel
for procedures or imaging. Devices remained in place for > 80% of the total
monitoring period and generated usable data > 50% of that time. CONCLUSIONS: A
standardized, bedside single burr hole approach to MMM was safe. Despite some
probe-specific recording limitations, MMM provided real-time measurements of
intracranial pressure, oxygenation, regional cerebral blood flow, brain
temperature, and function.
PMID- 29949002
TI - Early Hyperoxia in Patients with Traumatic Brain Injury Admitted to Intensive
Care in Australia and New Zealand: A Retrospective Multicenter Cohort Study.
AB - BACKGROUND: Early hyperoxia may be an independent risk factor for mortality in
critically ill traumatic brain injury (TBI) patients, although current data are
inconclusive. Accordingly, we conducted a retrospective cohort study to determine
the association between systemic oxygenation and in-hospital mortality, in
critically ill mechanically ventilated TBI patients. METHODS: Data were extracted
from the Australian and New Zealand Intensive Care Society Centre for Outcome and
Resource Evaluation Adult Patient Database. All adult TBI patients receiving
mechanical ventilation in 129 intensive care units between 2000 and 2016 were
included in analysis. The following data were extracted: demographics, illness
severity scores, physiological and laboratory measurements, institutional
characteristics, and vital status at discharge. In-hospital mortality was used as
the primary study outcome. The primary exposure variable was the 'worst' partial
arterial pressure of oxygen (PaO2) recorded during the first 24 h in ICU;
hyperoxia was defined as > 299 mmHg. Adjustment for illness severity utilized
multivariable logistic regression, the results of which are reported as the odds
ratio (OR) 95% CI. RESULTS: Data concerning 24,148 ventilated TBI patients were
extracted. By category of worst PaO2, crude in-hospital mortality ranged from
27.1% (PaO2 40-49 mmHg) to 13.3% (PaO2 140-159 mmHg). When adjusted for patient
and institutional characteristics, the only PaO2 category associated with a
significantly greater risk of death was < 40 mmHg [OR 1.52, 1.03-2.25]. A total
of 3117 (12.9%) patients were hyperoxic during the first 24 h in ICU, with a
crude in-hospital mortality rate of 17.8%. No association was evident in between
hyperoxia and mortality in adjusted analysis [OR 0.97 (0.86-1.11)]. CONCLUSIONS:
In this large multicenter cohort of TBI patients, hyperoxia in the first 24 h
after ICU admission was not independently associated with greater in-hospital
mortality. Hypoxia remains associated with greater in-hospital mortality risk and
should be avoided where possible.
PMID- 29949003
TI - Minority Patients are Less Likely to Undergo Withdrawal of Care After Spontaneous
Intracerebral Hemorrhage.
AB - BACKGROUND: Prior studies of patients in the intensive care unit have suggested
racial/ethnic variation in end-of-life decision making. We sought to evaluate
whether race/ethnicity modifies the implementation of comfort measures only
status (CMOs) in patients with spontaneous, non-traumatic intracerebral
hemorrhage (ICH). METHODS: We analyzed data from the Ethnic/Racial Variations of
Intracerebral Hemorrhage (ERICH) study, a prospective cohort study specifically
designed to enroll equal numbers of white, black, and Hispanic subjects. ICH
patients aged >= 18 years were enrolled in ERICH at 42 hospitals in the USA from
2010 to 2015. Univariate and multivariate logistic regression analyses were
implemented to evaluate the association between race/ethnicity and CMOs after
adjustment for potential confounders. RESULTS: A total of 2705 ICH cases (912
black, 893 Hispanic, 900 white) were included in this study (mean age 62 [SD 14],
female sex 1119 [41%]). CMOs patients comprised 276 (10%) of the entire cohort;
of these, 64 (7%) were black, 79 (9%) Hispanic, and 133 (15%) white (univariate p
< 0.001). In multivariate analysis, compared to whites, blacks were half as
likely to be made CMOs (OR 0.50, 95% CI 0.34-0.75; p = 0.001), and no
statistically significant difference was observed for Hispanics. All three
racial/ethnic groups had similar mortality rates at discharge (whites 12%, blacks
9%, and Hispanics 10%; p = 0.108). Other factors independently associated with
CMOs included age (p < 0.001), premorbid modified Rankin Scale (p < 0.001),
dementia (p = 0.008), admission Glasgow Coma Scale (p = 0.009), hematoma volume
(p < 0.001), intraventricular hematoma volume (p < 0.001), lobar (p = 0.032) and
brainstem (p < 0.001) location and endotracheal intubation (p < 0.001).
CONCLUSIONS: In ICH, black patients are less likely than white patients to have
CMOs. However, in-hospital mortality is similar across all racial/ethnic groups.
Further investigation is warranted to better understand the causes and
implications of racial disparities in CMO decisions.
PMID- 29949004
TI - Preventable Readmissions and Predictors of Readmission After Subarachnoid
Hemorrhage.
AB - OBJECTIVE: To estimate rates of all-cause and potentially preventable
readmissions up to 90 days after discharge for aneurysmal subarachnoid hemorrhage
(SAH) and medical comorbidities associated with readmissions BACKGROUND:
Readmission rate is a common metric linked to compensation and used as a proxy to
quality of care. Prior studies in SAH have reported 30-day readmission rates of 7
17% with a higher readmission risk among those with the higher SAH severity, >= 3
comorbidities, and non-home discharge. Intermediate-term rates, up to 90-days,
and the proportion of these readmissions that are potentially preventable are
unknown. Furthermore, the specific medical comorbidities associated with
readmissions are unknown. METHODS: Index SAH admissions were identified from the
2013 Nationwide Readmissions Database. All-cause readmissions were defined as any
readmission during the 30-, 60-, and 90-day post-discharge period. Potentially
preventable readmissions were identified using Prevention Quality Indicators
developed by the US Agency for Healthcare Research and Quality. Unadjusted and
adjusted Poisson models were used to identify factors associated with increased
readmission rates. RESULTS: Out of 9987 index admissions for SAH, 7949 (79%)
survived to discharge. The percentage of 30-, 60-, and 90-day all-cause
readmissions were 7.8, 16.6, and 26%, respectively. Up to 14% of readmissions in
the first 30 days were considered potentially preventable and acute conditions
(dehydration, bacterial pneumonia, and urinary tract infections) accounted for
over half, whereas acute cerebrovascular disease was the most common cause for
neurological return. In multivariable analysis, significant predictors of a
higher readmission rate included diabetes (rate ratio [RR] 1.09, 95% confidence
interval [CI] 1.03-1.15), congestive heart failure (RR 1.09, 1.003-1.18), and
renal impairment (RR 1.35, 1.13-1.61). Only discharge home was associated with a
lower readmission rate (RR 0.89, 0.85-0.93). CONCLUSIONS: SAH has a 30-day
readmission rate of 7.8% which continues to rise into the intermediate-term. A
low but constant proportion of readmissions are potentially preventable. Several
chronic medical comorbidities were associated with readmissions. Prospective
studies are warranted to clarify causal relationships.
PMID- 29949005
TI - Insight into Ping-Pong Gaze in the Neurosciences Intensive Care Unit.
PMID- 29949006
TI - Evaluation of a New Multiparameter Brain Probe for Simultaneous Measurement of
Brain Tissue Oxygenation, Cerebral Blood Flow, Intracranial Pressure, and Brain
Temperature in a Porcine Model.
AB - BACKGROUND: A novel multiparameter brain sensor (MPBS) allows the simultaneous
measurement of brain tissue oxygenation (ptiO2), cerebral blood flow (CBF),
intracranial pressure (ICP), and brain temperature with a single catheter. This
laboratory investigation evaluates the MPBS in an animal model in relation to
established reference probes. METHODS: The study group consisted of 17 juvenile
male pigs. Four MPBS and four reference probes were implanted per pig and
compared simultaneously. The measured parameters were challenged by standardized
provocations such as hyperoxia, dobutamine, and norepinephrine application,
hypercapnia and hypoxia in combination with and without a controlled cortical
impact (CCI) injury. Mean values over 2 min were collected for predefined time
points and were analyzed using Bland-Altman plots. RESULTS: The protocol was
successfully conducted in 15 pigs of which seven received CCI. ICP and ptiO2 were
significantly influenced by the provocations. Subtraction of MPBS from reference
values revealed a mean difference (limits of agreement) of 3.7 (- 20.5 to 27.9)
mm Hg, - 2.9 (- 7.9 to 2.1) mm Hg, and 5.1 (- 134.7 to 145.0) % for ptiO2, ICP,
and relative CBF, respectively. CONCLUSIONS: The MPBS is a promising measurement
tool for multiparameter neuromonitoring. The conducted study demonstrates the in
vivo functionality of the probe. Comparison with standard probes revealed a
deviation which is mostly analogous to other multiparameter devices. However,
further evaluation of the device is necessary before it can reliably be used for
clinical decision making.
PMID- 29949007
TI - Evaluation of STESS, mRSTESS, and EMSE to Predict High Disability and Mortality
at Hospital Discharge in Ecuadorian Patients with Status Epilepticus.
AB - BACKGROUND: Adequate identification of the severity of status epilepticus (SE)
contributes to individualized treatment. The scales most widely used for this
purpose are: Status Epilepticus Severity Score (STESS), Epidemiology-Based
Mortality Score in Status Epilepticus (EMSE) and modified Rankin Scale STESS
(mRSTESS). The aim of this study was to evaluate the performance of the STESS,
EMSE and mRSTESS scales to predict high disability and hospital mortality at
discharge (HD/HM). METHODS: A prospective study was conducted in which total of
41 patients were registered from November 2015 to January 2018 at Eugenio Espejo
Hospital. Clinical variables such as age, sex, clinical status at the beginning
of the SE, initial symptom of SE, as well as the STESS, mRSTESS and EMSE variant
scales were studied at the time of the diagnosis of SE. RESULTS: A total of 41
patients were evaluated, of which 8 (19.5%) had HD at hospital discharge and died
13 (31.7%) during their care. The area under the receiver operating
characteristic curve to predict HD/HM was 0.71 (95% CI (confidence interval) 0.55
0.87), 0.81 (95% CI 0.67-0.94), 0.89 (95% CI 0.79-0.99), 0.90 (95% CI 0.80-1.0),
0.89 (95% CI 0.78-0.99) for the STESS, mRSTESS, EMSE-EAC (etiology, age,
comorbidities), EMSE-EACEG (etiology, age, comorbidities, electroencephalography)
and EMSE-ECLEG (etiology, age, level of consciousness at pre-treatment,
electroencephalography), variants of EMSE, respectively. The binary logistic
regression demonstrated how the following cut-off points were determined: STESS
OR (odd ratio) 4.80 (p = 0.02), mRSTESS OR 7.89 (p = 0.00), EMSE-EAC OR 22.16 (p
= 0.00), EMSE-ECLEG OR 18.00 (p = 0.00), EMSE-EACEG OR 14 (p = 0.00).
CONCLUSIONS: All of the evaluated scales (STESS, mRSTESS, and EMSE) were shown to
be useful in predicting HD/HM. EMSE was observed to be the most effective of the
scales, with relative similarities among the variants.
PMID- 29949008
TI - Combination of Clinical Exam, MRI and EEG to Predict Outcome Following Cardiac
Arrest and Targeted Temperature Management.
AB - BACKGROUND: Despite the widespread adoption of targeted temperature management
(TTM), coma after cardiac arrest remains a common problem with a high proportion
of patients suffering substantial disability. Prognostication after cardiac
arrest, particularly the identification of patients with likely good outcome,
remains difficult. METHODS: We performed a retrospective study of 78 patients who
underwent TTM after cardiac arrest and were evaluated with both
electroencephalography (EEG) and magnetic resonance imaging (MRI). We
hypothesized that combining malignant versus non-malignant EEG classification
with clinical exam and quantitative analysis of apparent diffusion coefficient
(ADC) and fluid-attenuated inversion recovery imaging would improve prognostic
ability. RESULTS: Consistent with prior literature, presence of a malignant EEG
pattern was 100% specific for poor outcome. We found that decreased whole brain
ADC signal intensity was associated with poor outcome (853 +/- 14 vs. 950 +/-
17.5 mm2/s, p < 0.0001). Less than 15% total brain volume with ADC signal
intensity < 650 mm2/s was predictive of good outcome with 100% sensitivity, 51%
specificity and an area under the curve of 0.787. A model combining this ADC
marker with non-malignant EEG and flexor-or-better motor response was 100%
sensitive and 91.1% specific for good outcome following cardiac arrest and
targeted temperature management. CONCLUSION: We conclude that in the absence of
malignant EEG findings, combination of physical exam and MRI findings can be a
useful to identify those patients who have potential for recovery. Variability in
timing of imaging and findings in different modalities argue for the need for
future prospective studies of multimodal outcome prediction after cardiac arrest.
PMID- 29949009
TI - Impact of Acute Cardiac Complications After Subarachnoid Hemorrhage on Long-Term
Mortality and Cardiovascular Events.
AB - BACKGROUND: Cardiac complications frequently occur after subarachnoid hemorrhage
(SAH) and are associated with an increased risk of neurological complications and
poor outcomes. The aim of this study was to evaluate the impact of acute cardiac
complications after SAH on long-term mortality and cardiovascular events.
METHODS: All patients admitted to our Neuro intensive care unit with verified SAH
from January 2010 to April 2015, and electrocardiogram, echocardiogram, and
troponin T or NTproBNP data obtained within 72 h of admission were included in
the study. Mortality data were obtained from the Swedish population register.
Data regarding cause of death and hospitalization for cardiovascular events were
obtained from the Swedish Board of Health and Welfare. RESULTS: A total of 455
patients were included in the study analysis. There were 102 deaths during the
study period. Cardiac troponin release (HR 1.08, CI 1.02-1.15 per 100 ng/l, p =
0.019), NTproBNP (HR 1.05, CI 1.01-1.09 per 1000 ng/l, p = 0.018), and ST-T
abnormalities (HR 1.53, CI 1.02-2.29, p = 0.040) were independently associated
with an increased risk of death. However, these associations were significant
only during the first 3 months after the hemorrhage. Cardiac events were observed
in 25 patients, and cerebrovascular events were observed in 62 patients during
the study period. ST-T abnormalities were independently associated with an
increased risk of cardiac events (HR 5.52, CI 2.07-14.7, p < 0.001), and stress
cardiomyopathy was independently associated with an increased risk of
cerebrovascular events (HR 3.65, CI 1.55-8.58, p = 0.003). CONCLUSION: Cardiac
complications after SAH are associated with an increased risk of short-term
death. Patients with electrocardiogram abnormalities and stress cardiomyopathy
need appropriate follow-up for the identification of cardiac disease or risk
factors for cardiovascular disease.
PMID- 29949010
TI - Safety and Efficiency of Intravenous Push Lacosamide Administration.
AB - BACKGROUND/OBJECTIVE: Intravenous (IV) lacosamide use for status epilepticus has
increased in recent years and is recommended for refractory status epilepticus by
current guidelines. Per the lacosamide package labeling, the preferred route of
administration is diluted and infused over 30-60 min; however, administration
undiluted is also acceptable and recent literature demonstrated safety at a
maximum rate of 80 mg per minute (Kellinghaus et al. in Acta Neurol Scand 123:137
141, 2011). Undiluted administration as an IV push has potential to increase
efficiency of administration to patients needing urgent seizure control since it
may be dispensed from automatic dispensing cabinets in patient care areas. This
study aims to compare safety outcomes and efficiency of administration in
patients receiving lacosamide IV push compared to IV piggyback. METHODS: We
present a single-center, retrospective cohort study of patients receiving
lacosamide via IV piggyback or IV push from June 2016 to July 2017. Baseline
characteristics, data related to potential safety concerns and timing of
ordering, verification, and administration were collected. The primary safety
outcomes were incidence of infusion site reactions, hypotension (systolic blood
pressure [SBP] < 90 mm Hg), and bradycardia (heart rate [HR] < 50 beats per
minute) documented within 2 h of each lacosamide dose. Secondary safety outcomes
included the incidence of PR interval prolongation in patients with at least one
electrocardiogram measured. The primary efficiency outcome was the time between
order verification and administration. RESULTS: Patients in the IV piggyback (n =
88) and IV push (n = 78) groups had similar baseline characteristics, initial
dose, SBP, and HR. Hypotension (8 vs. 10.3%) and bradycardia (2.3 vs. 2.6%) rates
were similar among both groups (p > 0.05). Only one patient in each group had
documented PR prolongation, and no documented infusion reactions occurred. Median
time from order verification to administration was significantly reduced in the
IV push group (35 min vs. 1 h 49 min; p < 0.001). CONCLUSIONS: Administration of
lacosamide via IV push results in similar adverse effect rates to IV piggyback
preparations with more efficient time to administration.
PMID- 29949011
TI - Accuracy and Safety of External Ventricular Drain Placement by Physician
Assistants and Nurse Practitioners in Aneurysmal Acute Subarachnoid Hemorrhage.
AB - BACKGROUND: In the current dynamic health environment, increasing number of
procedures are being completed by advanced practitioners (nurse practitioners and
physician assistants). This is the first study to assess the clinical outcomes
and safety of external ventricular drain (EVD) placements by specially trained
advanced practitioners. OBJECTIVE: Compare the safety and outcomes of EVD
placement by advanced practitioners in patients with subarachnoid hemorrhage
(SAH). METHODS: A cohort comparison study was performed from an aneurysmal SAH
database selecting patients treated with EVD from a single major academic
institution in the USA between June 2007 and June 2017. Safety, accuracy, and
complications of EVD placement were compared between advanced practitioners and
neurosurgical physicians (attending neurosurgeon and subspecialty clinical
fellow). Statistical analysis was performed using the Mann-Whitney test for
continuous variables and chi2 test for categorical variables, with p values set
at < 0.05 for significance. RESULTS: We identified 203 patients for this cohort
with 238 EVD placements; eighty-seven (36.6%) placements were performed by
advanced practitioners and 151 (63.4%) by neurosurgeons. Most of the
ventriculostomies were placed in the emergency room (n = 114; 47.9%). Additional
procedures performed concurrently with the EVD placements were significantly
higher among the physicians' group (21.8 vs. 4.6%; p < 0.001). Bedside placement
and usage of Ghajar guide were significantly higher among advanced practitioner's
(58.3 vs. 98.9 and 9.9 vs. 64.4%, respectively, with a p < 0.001 for both). There
were, however, no significant differences in terms of the number of attempts for
insertion, intraprocedural complications, tract hemorrhages, accuracy, infection
rates, catheter dislodgments, and need for repositioning/replacement of EVD.
CONCLUSION: After appropriate training, EVD placement can be safely performed by
advanced practitioners with an adequate accuracy of placement.
PMID- 29949012
TI - Women and acute kidney injury in myocardial infarction.
AB - BACKGROUND: Data on the relationship between gender and acute kidney injury (AKI)
in patients with myocardial infarction (MI) undergoing percutaneous coronary
intervention (PCI) are conflicting and inconclusive. The contrast volume-to
estimated glomerular filtration rate ratio (CV/GFR) was shown to predict AKI in
patients with MI undergoing PCI. We assessed gender-based differences in AKI and
evaluated the association between the CV/GFR and AKI in MI patients undergoing
PCI. METHODS: We retrospectively studied 4675 consecutive patients with MI who
underwent PCI between January 2007 and December 2015. The incidence of AKI and
CV/GFR in men and women were compared. Data were analyzed using descriptive
statistics. RESULTS: Women suffered more AKI than men [152 (10.5%) women suffered
AKI compared to 252 (7.8%) men; p = 0.003]. After adjustment for potential
confounders, female gender was identified as an independent predictive factor for
AKI. CV/GFR was higher in women (2.57 +/- 1.95 in women vs. 2.25 +/- 1.60 in men;
p < 0.0001) and predicted AKI. CONCLUSION: AKI occurs more often in women than
men with MI undergoing PCI. Female gender independently predicted AKI in our
analysis. A high CV/GFR denotes a group of patients who are at higher risk of AKI
after PCI. CV/GFR was significantly higher in women, which may help to explain
their worse outcome as regards AKI.
PMID- 29949014
TI - Cardiovascular Safety of Empagliflozin Versus Dipeptidyl Peptidase-4 (DPP-4)
Inhibitors in Type 2 Diabetes: Systematic Literature Review and Indirect
Comparisons.
AB - INTRODUCTION: Clinical trials conducted in patients with type 2 diabetes (T2DM)
treated with glucose-lowering drugs and examining cardiovascular-related outcomes
have yielded mixed results. In this work, we aimed to assess the relative
treatment effects of empagliflozin versus sitagliptin and saxagliptin (dipeptidyl
peptidase-4 (DPP-4) inhibitors) on cardiovascular-related outcomes in patients
with T2DM. METHODS: We conducted a systematic literature review to identify
clinical trials assessing cardiovascular-related outcomes for sitagliptin-,
saxagliptin-, and empagliflozin-treated patients with T2DM. A network meta
analysis of indirect treatment comparisons was conducted in a Bayesian framework.
Hazard ratios (HR) and 95% credible intervals (CrI) were computed for six
cardiovascular-related outcomes to estimate the relative efficacies of these
agents. RESULTS: Empagliflozin showed a statistically significant superiority
over saxagliptin (HR 0.60; 95% CrI 0.46-0.80) and sitagliptin (HR 0.60; 95% CrI
0.46-0.79) to reduce the risk for cardiovascular-related mortality. For all-cause
mortality, empagliflozin showed a statistically significant risk reduction
compared to saxagliptin (HR 0.61; 95% CrI 0.49-0.76) and sitagliptin (HR 0.67;
95% CrI 0.54-0.83). A similar pattern was observed in the risk reduction for
hospitalization due to heart failure, where empagliflozin was found to be
statistically significantly superior to saxagliptin (HR 0.51; 95% CrI 0.37-0.70)
and sitagliptin (HR 0.65; 95% CrI 0.47-0.90). Empagliflozin was not statistically
significantly different to sitagliptin and saxagliptin with regard to the risk of
a composite endpoint composed of death, stroke or myocardial infarction.
CONCLUSION: In this indirect comparison to the DPP-4 inhibitors saxagliptin and
sitagliptin, empagliflozin significantly lowered the risk of cardiovascular
related mortality, all-cause mortality and hospitalizations due to heart failure.
FUNDING: Boehringer Ingelheim GmbH.
PMID- 29949015
TI - Long-Term Effect of the Color Record Method in Self-Monitoring of Blood Glucose
on Metabolic Parameters in Type 2 Diabetes: A 2-Year Follow-up of the Color
IMPACT Study.
AB - INTRODUCTION: This article evaluates the potential long-term effect of two
different color indication methods for self-monitoring of blood glucose (SMBG),
the color record (CR) and color display (CD), on metabolic parameters in insulin
treated type 2 diabetes in a post-intervention period. METHODS: 101 participants
with type 2 diabetes who completed the Color IMPACT study were enrolled in a 2
year comparison follow-up study. Participants continued SMBG with their usual
diabetes care. The study outcomes were differences in change in HbA1c levels,
blood pressure (BP), body weight and lipid profiles between the CR and non-CR
arms and the CD and non-CD arms during a 1- and 2-year period of the study.
RESULTS: 98 participants were analyzed. Reductions in HbA1c levels, systolic BP
and low-density lipoprotein cholesterol levels were maintained in the CR arm by -
0.40% (95% CI: - 0.73 to - 0.06, p = 0.020), -1 3.2 mmHg (95% CI: - 24.1 to -
2.3, p = 0.019), - 11.4 mg/dl (95% CI: - 18.1 to - 4.6, p = 0.001), respectively,
in a 1-year period. However, HbA1c and BP returned to the baseline levels during
an additional 1-year period. In contrast, there were no significant changes in
outcome in the CD arm during the study period. CONCLUSION: Intervention promoting
self-action such as the color record method in SMBG sustains a beneficial effect
on metabolic parameters after the intervention. This long-term effect is helpful
for people with type 2 diabetes to manage their diabetes ABCs (HbA1c, BP,
cholesterol) and to prevent diabetic complications. TRIAL REGISTRATION: UMIN
clinical trials registry identifier, UMIN000006865.
PMID- 29949013
TI - A best-practice position statement on pregnancy after kidney transplantation:
focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the
Italian Society of Nephrology.
AB - Kidney transplantation (KT) is often considered to be the method best able to
restore fertility in a woman with chronic kidney disease (CKD). However,
pregnancies in KT are not devoid of risks (in particular prematurity, small for
gestational age babies, and the hypertensive disorders of pregnancy). An ideal
profile of the potential KT mother includes "normal" or "good" kidney function
(usually defined as glomerular filtration rate, GFR >= 60 ml/min), scant or no
proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood
pressure (one drug only and no sign of end-organ damage), no recent acute
rejection, good compliance and low-dose immunosuppression, without the use of
potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an
interval of at least 1-2 years after transplantation. In this setting, there is
little if any risk of worsening of the kidney function. Less is known about how
to manage "non-ideal" situations, such as a pregnancy a short time after KT, or
one in the context of hypertension or a failing kidney. The aim of this position
statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology
is to review the literature and discuss what is known about the clinical
management of CKD after KT, with particular attention to women who start a
pregnancy in non-ideal conditions. While the experience in such cases is limited,
the risks of worsening the renal function are probably higher in cases with
markedly reduced kidney function, and in the presence of proteinuria. Well
controlled hypertension alone seems less relevant for outcomes, even if its
effect is probably multiplicative if combined with low GFR and proteinuria. As in
other settings of kidney disease, superimposed preeclampsia (PE) is differently
defined and this impairs calculating its real incidence. No specific difference
between non-teratogen immunosuppressive drugs has been shown, but calcineurin
inhibitors have been associated with foetal growth restriction and low birth
weight. The clinical choices in cases at high risk for malformations or kidney
function impairment (pregnancies under mycophenolic acid or with severe kidney
function impairment) require merging clinical and ethical approaches in which,
beside the mother and child dyad, the grafted kidney is a crucial "third
element".
PMID- 29949016
TI - A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus
Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and
Markers Associated with Bodyweight Loss.
AB - INTRODUCTION: The sodium-glucose cotransporter 2 inhibitor dapagliflozin and the
glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduce bodyweight via
differing and complementary mechanisms. This post hoc analysis investigated the
metabolic effects and baseline associations with bodyweight loss on
coadministration of dapagliflozin and exenatide once weekly (QW) among adults
with obesity and without diabetes. METHODS: In the primary trial, adults with
obesity and without diabetes [n = 50; 18-70 years; body mass index (BMI) 30-45
kg/m2] were randomized to double-blind oral dapagliflozin 10 mg (DAPA) once daily
plus subcutaneous long-acting exenatide 2 mg QW (ExQW) or placebo over 24 weeks,
followed by an open-label extension from 24-52 weeks during which all
participants received active treatment. Primary results have been published
previously. This analysis evaluated: (1) the effects of DAPA + ExQW on changes in
substrates [free fatty acids (FFAs), glycerol, beta-OH-butyrate, and glucose],
hormones (glucagon and insulin), and insulin secretion [insulinogenic index
(IGI)] via an oral glucose tolerance test (OGTT) and (2) associations between
bodyweight loss and baseline characteristics (e.g., BMI), single-nucleotide
polymorphisms (SNPs) associated with the GLP-1 pathway, and markers of glucose
regulation. RESULTS: Compared with placebo at 24 weeks, 2-h FFAs post-OGTT
increased (mean difference, +20.4 MUmol/l; P < 0.05), and fasting glucose, 2-h
glucose post-OGTT, and glucose area under the concentration-time curve (AUC)
decreased with DAPA + ExQW [mean differences, -0.68 mmol/l [P < 0.001], -2.20
mmol/l (P < 0.01), and -306 mmol/l min (P < 0.001), respectively]. Glucagon,
glycerol, beta-OH-butyrate, and IGI did not differ by treatment group at 24
weeks. Over 52 weeks, DAPA + ExQW decreased fasting insulin, 2-h post-OGTT
insulin, and insulin AUC. Among DAPA + ExQW-treated participants, for each copy
of the SNP variant rs10010131 A allele (gene WFS1), bodyweight decreased by 2.4
kg (P < 0.05). Lower BMI and a lower IGI were also associated with greater
bodyweight loss with DAPA + ExQW. CONCLUSIONS: Metabolic effects with DAPA + ExQW
included less FFA suppression versus placebo during the OGTT, suggesting
compensatory lipid mobilization for energy production when glucose availability
was reduced because of glucosuria. The expected increase in glucagon with DAPA
did not occur with DAPA + ExQW coadministration. Bodyweight loss with DAPA + ExQW
was associated with the SNP variant rs10010131 A allele, lower baseline adiposity
(BMI), and lower baseline insulin secretion (IGI). These findings require further
validation. FUNDING: AstraZeneca.
PMID- 29949017
TI - Executive function underlies both perspective selection and calculation in Level
1 visual perspective taking.
AB - Previous research has suggested that the calculation of another's perspective is
cognitively efficient, whereas perspective selection (selection of a particular
perspective, self or other) is associated with executive function, particularly
inhibitory control. However, research has not previously tested how perspective
calculation and selection may be associated with another key executive function,
working memory. In the present study (N = 54 adult participants), we administered
a Level-1 visual perspective task in a dual-task paradigm in which the secondary
task required working memory. The results suggest that executive function is
associated with both perspective calculation and perspective selection, contrary
to previous evidence from similar dual-task studies that had used inhibitory
control and attention-based secondary tasks. This contrast may suggest that
working memory capacity facilitates perspective-taking. Furthermore, it may
follow that the notion of simple perspective-taking is distinct from more the
complex and cognitively demanding "theory of mind." Research of this nature
warrants further investigation.
PMID- 29949018
TI - Gaze following in multiagent contexts: Evidence for a quorum-like principle.
AB - Research shows that humans spontaneously follow another individual's gaze.
However, little remains known on how they respond when multiple gaze cues diverge
across members of a social group. To address this question, we presented
participants with displays depicting three (Experiment 1) or five (Experiment 2)
agents showing diverging social cues. In a three-person group, one individual
looking at the target (33% of the group) was sufficient to elicit gaze
facilitated target responses. With a five-person group, however, three
individuals looking at the target (60% of the group) were necessary to produce
the same effect. Gaze following in small groups therefore appears to be based on
a quorum-like principle, whereby the critical level of social information needed
for gaze following is determined by a proportion of consistent social cues scaled
as a function of group size. As group size grows, greater agreement is needed to
evoke joint attention.
PMID- 29949019
TI - Correction to: Clinical Pharmacokinetic Characteristics of Cebranopadol, a Novel
First-in-Class Analgesic.
AB - For each simulation, PK profiles from 1000 subjects were simulated based on a
titration scheme.
PMID- 29949020
TI - Sub-threshold depolarizing pre-pulses can enhance the efficiency of biphasic
stimuli in transcutaneous neuromuscular electrical stimulation.
AB - There is multiple evidence in the literature that a sub-threshold pre-pulse,
delivered immediately prior to an electrical stimulation pulse, can alter the
activation threshold of nerve fibers and motor unit recruitment characteristics.
So far, previously published works combined monophasic stimuli with sub-threshold
depolarizing pre-pulses (DPPs) with inconsistent findings-in some studies, the
DPPs decreased the activation threshold, while in others it was increased. This
work aimed to evaluate the effect of DPPs during biphasic transcutaneous
electrical stimulation and to study the possible mechanism underlying those
differences. Sub-threshold DPPs between 0.5 and 15 ms immediately followed by
biphasic or monophasic pulses were administered to the tibial nerve; the
electrophysiological muscular responses (motor-wave, M-wave) were monitored via
electromyogram (EMG) recording from the soleus muscle. The data show that, under
the specific studied conditions, DPPs tend to lower the threshold for nerve fiber
activation rather than elevating it. DPPs with the same polarity as the leading
phase of biphasic stimuli are more effective to increase the sensitivity. This
work assesses for the first time the effect of DPPs on biphasic pulses, which are
required to achieve charge-balanced stimulation, and it provides guidance on the
effect of polarity and intensity to take full advantage of this feature.
Graphical abstract In this work, the effect of sub-threshold depolarizing pre
pulses (DPP) is investigated in a setup with transcutaneous electrical
stimulation. We found that, within the tested 0-15 ms DPP duration range, the
DPPs administered immediately before biphasic pulses proportionally increase the
nerve excitability as visible in the M-waves recorded from the soleus muscle.
Interestingly, these findings oppose published results, where DPPs, administered
immediately before monophasic stimuli via implanted electrodes, led to decrease
of nerve excitability.
PMID- 29949021
TI - Dynamic ensemble selection of learner-descriptor classifiers to assess curve
types in adolescent idiopathic scoliosis.
AB - While classification is important for assessing adolescent idiopathic scoliosis
(AIS), it however suffers from low interobserver and intraobserver reliability.
Classification using ensemble methods may contribute to improving reliability
using the proper 2D and 3D images of spine curvature features. In this study, we
present two new techniques to describe the spine, namely, leave-one-out and fan
leave-one-out. Using these techniques, three descriptors are computed from a
stereoradiographic 3D reconstruction to describe the relationship between a
vertebra and its neighbors. A dynamic ensemble selection method is introduced for
automatic spine classification. The performance of the method is evaluated on a
dataset containing 962 3D spine models categorized according to three curve
types. With a log loss of 0.5623, the dynamic ensemble selection outperforms
voting and stacking ensemble learning techniques. This method can improve
intraobserver and interobserver reliability, identify the best combination of
descriptors for characterizing spine curve types, and provide assistance to
clinicians in the form of information to classify borderline curvature types.
Graphical abstract ?.
PMID- 29949022
TI - Complete mechanical characterization of an external hexagonal implant connection:
in vitro study, 3D FEM, and probabilistic fatigue.
AB - The aim of this study was to fully characterize the mechanical behavior of an
external hexagonal implant connection (o3.5 mm, 10-mm length) with an in vitro
study, a three-dimensional finite element analysis, and a probabilistic fatigue
study. Ten implant-abutment assemblies were randomly divided into two groups,
five were subjected to a fracture test to obtain the maximum fracture load, and
the remaining were exposed to a fatigue test with 360,000 cycles of 150 +/- 10 N.
After mechanical cycling, all samples were attached to the torque-testing machine
and the removal torque was measured in Newton centimeters. A finite element
analysis (FEA) was then executed in ANSYS(r) to verify all results obtained in
the mechanical tests. Finally, due to the randomness of the fatigue phenomenon, a
probabilistic fatigue model was computed to obtain the probability of failure
associated with each cycle load. FEA demonstrated that the fracture corresponded
with a maximum stress of 2454 MPa obtained in the in vitro fracture test. Mean
life was verified by the three methods. Results obtained by the FEA, the in vitro
test, and the probabilistic approaches were in accordance. Under these
conditions, no mechanical etiology failure is expected to occur up to 100,000
cycles. Graphical abstract ?.
PMID- 29949023
TI - Classification of pressure ulcer tissues with 3D convolutional neural network.
AB - A 3D convolution neural network (CNN) of deep learning architecture is supplied
with essential visual features to accurately classify and segment granulation,
necrotic eschar, and slough tissues in pressure ulcer color images. After finding
a region of interest (ROI), the features are extracted from both the original and
convolved with a pre-selected Gaussian kernel 3D HSI images, combined with first
order models of current and prior visual appearance. The models approximate
empirical marginal probability distributions of voxel-wise signals with linear
combinations of discrete Gaussians (LCDG). The framework was trained and tested
on 193 color pressure ulcer images. The classification accuracy and robustness
were evaluated using the Dice similarity coefficient (DSC), the percentage area
distance (PAD), and the area under the ROC curve (AUC). The obtained preliminary
DSC of 92%, PAD of 13%, and AUC of 95% are promising. Graphical Abstract The
Classification of Pressure Ulcer Tissues Based on 3D Convolutional Neural
Network.
PMID- 29949024
TI - The Value of Negative Diagnosis in Thyroid Fine-Needle Aspiration: a
Retrospective Study with Histologic Follow-Up.
AB - The Bethesda System for reporting thyroid cytopathology (BSRTC) predicts an
incidence of malignancy of less than 5% in thyroid nodules with a benign
diagnosis on fine-needle aspiration (FNA). However, recent series have suggested
that the true rate of malignancy might be significantly higher in this category
of patients. We reviewed our experience by performing a retrospective analysis of
patients with benign thyroid FNA results who underwent thyroidectomy between 2008
and 2013 at a large academic center. Information including demographics,
ultrasound features, FNA diagnosis, and surgical follow-up information were
recorded. Slides were reviewed on cytology-histology discrepant cases, and it was
determined whether the discrepancy was due to sampling or interpretation error. A
total of 802 FNA cases with a benign diagnosis and surgical follow-up were
identified. FNA diagnoses included 738 cases of benign goiter and 64 cases of
lymphocytic thyroiditis. On subsequent surgical resection, 144 cases were found
to be neoplastic, including 117 malignant cases. False negative, defined as
interpretation error and inadequate biopsy of the nodule harboring malignancy,
was 6%. When cases of noninvasive follicular thyroid neoplasm with papillary-like
nuclear features (NIFTP) were excluded from the analysis, false-negative rate was
5%. When microPTC cases were excluded, false-negative rate was 3% and was
slightly less than 3% when both microPTC and NIFTP cases were excluded from the
analysis. Retrospective review of neoplastic cases showed that 57% were due to
sampling error and 43% were due to interpretation error. Interpretation error was
more likely to occur in follicular patterned neoplasms (75%), while sampling
error was more common in non-follicular variants of papillary thyroid carcinoma
(non-FVPTC) (61%). With the exclusion of microPTC, interpretation errors were
still more likely to occur in follicular neoplasms (79%) but there was no
significant difference in sampling error between non-FVPTC (37%) and follicular
patterned neoplasms (42%). Tumor size was larger in cases with interpretation
error (mean = 2.3 cm) compared to cases with sampling error (mean = 1.4 cm). This
study shows that the false-negative rate of thyroid FNA at our institution is not
significantly above the rate suggested by the BSRTC. Interpretation errors were
more likely to occur in follicular patterned neoplasms, while non-FVPTC was more
frequently found in false negative cases due to inadequate sampling.
PMID- 29949025
TI - The Italian version of the quick mild cognitive impairment (Qmci-I) screen:
normative study on 307 healthy subjects.
AB - OBJECTIVE: To devise an Italian version of the quick mild cognitive impairment
screen (Qmci) and to obtain normative data. METHODS: An Italian version of the
Qmci screen (Qmci-I) was administered to 307 subjects free from cognitive
impairment. The normative sample was divided into three age levels (50-59; 60-69
and 70-80 years) and four education levels (3-5; 6-8; 9-13; >13 years of school
attendance). Multiple regression analyses were used to evaluate the effect of
age, sex and schooling on Qmci-I scores (overall and by domains) and to calculate
cut-off values, with reference to the confidence interval on the fifth centile.
RESULTS: The mean Qmci-I score was 64/100 (SD = 11). The age variable showed a
significant negative effect on the overall Qmci-I score, with older people
performing worse than younger ones. Conversely, education was associated with
higher scores. Significant effects of age and education affected logical memory
alone. For the other domains, the following effects were found: (1) higher age
associated with lower scores on delayed recall; (2) higher education levels
associated with higher scores on immediate recall, clock drawing and word
fluency. The adjusted cut-off score for the Qmci-I screen in this sample was
49.4. Qmci-I scores were weakly correlated with those of MMSE (rho = 0.20).
CONCLUSIONS: The Qmci-I is a rapid and multi-domain short cognitive screening
instrument useful for evaluating cognitive functions. However, like other
screening tools, it is significantly influenced by age and education, requiring
normative data and correction of values when used in the clinical practice.
PMID- 29949026
TI - Surgical delay is a risk factor of delirium in hip fracture patients with mild
moderate cognitive impairment.
AB - AIM: To investigate the relationship between onset of delirium and time to
surgery in hip fracture (HF) patients with a different degree of cognitive
impairment. METHODS: Retrospective analysis of a prospective database of 939
older adults, aged >= 75 years admitted with a fragility HF. Subjects underwent a
Comprehensive Geriatric Assessment on admission, evaluating health status,
prefracture functional status in basic and instrumental activities of daily
living, and walking ability. According to the Short Portable Mental Status
Questionnaire score, patients were stratified into three categories: cognitively
healthy (0-2 errors), mildly to moderately impaired (3-7 errors) and severely
impaired (8-10 errors). Time to surgery (from admission) was expressed as days.
The occurrence of delirium was ascertained daily by Confusion Assessment Method.
RESULTS: Two hundred ninety-two (31.1%) patients experienced delirium during in
hospital stay. They were older, with a higher degree of comorbidity and
functional impairment compared to patients without delirium. In multivariate
analysis, surgical delay resulted a significant independent risk factor for
delirium (HR 1.11, 95% CI 1.01-1.24), along with age, prefracture functional
disability and cognitive impairment. When the analysis was performed accounting
for the cognitive categories, surgical delay demonstrated to increase the risk of
delirium only in the subcategory of mildly to moderately impaired patients, while
no significant effect was demonstrated in patients cognitively healthy or
severely impaired. CONCLUSIONS: The study supports the concept that older adults
with HF should undergo surgery quickly. Patients with mild-to-moderate cognitive
impairment should be primarily considered as the best target for interventions
aiming to reduce time to surgery.
PMID- 29949027
TI - Pentoxifylline in prosthetic valve: a case report.
PMID- 29949028
TI - Correction to: The prevalence and health burden of malnutrition in Belgian older
people in the community or residing in nursing homes: results of the NutriAction
II study.
AB - In the original publication, table row alignment was incorrectly formatted for
all the tables. The corrected tables are given below.
PMID- 29949029
TI - Early extensive gyral calcification in ischemic stroke.
PMID- 29949030
TI - Response of the authors to the comments of Josef Josef Finsterer and Sinda
Zarrouk-Mahjoub on NeuroImage "Cerebral arterial and venous MRI abnormalities in
MELAS".
PMID- 29949031
TI - Median nerve ultrasound in carpal tunnel syndrome with normal electrodiagnostic
tests.
AB - INTRODUCTION: To evaluate the ultrasound findings of the median nerve in patients
with clinical assigned carpal tunnel syndrome but normal nerve conduction
studies. METHODS: This prospective, cross-sectional study involved 41 patients
(51 hands) with clinically assigned CTS and normal nerve conduction studies and
20 healthy controls (30 hands). Ultrasonography was performed in all
participants, and cross-sectional area (CSA), hypoechogenicity, and mobility of
the median nerve were evaluated. All patients were assessed with Boston Carpal
Tunnel Questionnaire (BCTQ). RESULTS: CSA of the median nerve in the wrist was
significantly higher in the patient group when compared to the control group.
Echogenicity and mobility were significantly decreased in the patient group.
Ultrasound abnormalities were positively correlated with clinical features. A
significant correlation was observed among sensory loss, provocative tests, body
mass index, BCTQ, and high CSA. CONCLUSION: US can help the clinicians with the
diagnosis of carpal tunnel syndrome in patients with clinical symptoms but
negative nerve conduction study results.
PMID- 29949032
TI - Factors associated with deterioration of health-related quality of life in
multiple system atrophy: 1-year follow-up study.
AB - The aim of this study was to identify the main contributors to the health-related
quality of life (HRQoL) in multiple system atrophy with predominant parkinsonism
(MSA-P) and to determine the usefulness of SF-36 in capturing the HRQoL changes
over 1-year follow-up. A total of 45 MSA-P and 150 Parkinson's disease (PD)
patients were studied. The hierarchical multiple regression analysis was
conducted to identify predictors of the SF-36 total score. The magnitude of any
change for the HRQoL over 1-year of follow-up, was calculated as an effect size.
The average scores for each SF-36 domains, except for the bodily pain, were lower
in MSA-P than in PD patients (p < 0.05). The most important predictors of HRQoL
in MSA-P, were female gender, older age at onset, SCOPA-AUT score and UMSARS IV,
which together with other selected clinical variables accounted for 84% of the
variance in the total SF-36 score in the final model in hierarchical analyses.
During the 1-year follow-up, the SF 36 was found capable of detecting changes in
MSA-P. Our study provided some new insights into potential predictors of the
HRQoL and its longitudinal changes in MSA-P, which should be considered when
healthcare programs are developed.
PMID- 29949033
TI - Bilateral stereotypy after unilateral cerebellar infarction.
PMID- 29949034
TI - Location, length, and enhancement: systematic approach to differentiating
intramedullary spinal cord lesions.
AB - PURPOSE: Intramedullary spinal cord abnormalities are often challenging to
diagnose. Spinal cord biopsy is a high-risk procedure with the potential to cause
permanent neurological injury. Magnetic resonance imaging is the modality of
choice for diagnosis and preoperative assessment of patients with spinal cord
abnormalities. The radiologist's ability to narrow the differential diagnosis of
spinal cord abnormalities has the potential to save patients from invasive
approaches for diagnosis and also guide appropriate management. APPROACH/METHODS:
This article will provide a systematic approach to the evaluation of
intramedullary spinal cord lesions-with emphasis on location, length and segment
distribution, and enhancement pattern-to help narrow the differential diagnosis.
In doing so, we will review various spinal cord pathologies, including
demyelinating and metabolic conditions, neoplasms, and vascular lesions. Although
intramedullary spinal cord abnormalities can be a challenge for the radiologist,
a systematic approach to the differential diagnosis with a focus on lesion
location, cord length and segment involvement, as well as enhancement pattern,
can greatly help narrow the differential diagnosis, if not synch the diagnosis.
This strategy will potentially obviate the need for an invasive approach to
diagnosis and help guide treatment. TEACHING POINTS: * Imaging diagnosis of
intramedullary spinal cord lesions could obviate cord biopsy. * Evaluation of
cord lesions should focus on location, length, and enhancement pattern. * In
demyelination, the degree of cross-sectional involvement is a distinguishing
feature.
PMID- 29949035
TI - Tracking the glossopharyngeal nerve pathway through anatomical references in
cross-sectional imaging techniques: a pictorial review.
AB - : The glossopharyngeal nerve (GPN) is a rarely considered cranial nerve in
imaging interpretation, mainly because clinical signs may remain unnoticed, but
also due to its complex anatomy and inconspicuousness in conventional cross
sectional imaging. In this pictorial review, we aim to conduct a comprehensive
review of the GPN anatomy from its origin in the central nervous system to
peripheral target organs. Because the nerve cannot be visualised with
conventional imaging examinations for most of its course, we will focus on the
most relevant anatomical references along the entire GPN pathway, which will be
divided into the brain stem, cisternal, cranial base (to which we will add the
parasympathetic pathway leaving the main trunk of the GPN at the cranial base)
and cervical segments. For that purpose, we will take advantage of cadaveric
slices and dissections, our own developed drawings and schemes, and computed
tomography (CT) and magnetic resonance imaging (MRI) cross-sectional images from
our hospital's radiological information system and picture and archiving
communication system. TEACHING POINTS: * The glossopharyngeal nerve is one of the
most hidden cranial nerves. * It conveys sensory, visceral, taste,
parasympathetic and motor information. * Radiologists' knowledge must go beyond
the limitations of conventional imaging techniques. * The nerve's pathway
involves the brain stem, cisternal, skull base and cervical segments. *
Systematising anatomical references will help with nerve pathway tracking.
PMID- 29949037
TI - Correction to: Combination Glucose-Lowering Therapy Plans in T2DM: Case-Based
Considerations.
AB - The article "Combination Glucose-Lowering Therapy Plans in T2DM: Case-Based
Considerations".
PMID- 29949036
TI - Validation of the educational effectiveness of a mobile learning app to improve
knowledge about MR image quality optimisation and artefact reduction.
AB - AIM: The aim was to design an app-based eLearning tool to provide radiographers
with information about the physical basis of MR artefacts and practical
elimination or/and minimisation strategies to optimise image quality, and to
evaluate the impact of a smartphone app on radiographers' knowledge. METHODS: The
study used the comparison-experimental approach (pre- and post-test). Thirty-five
MR radiographers independently reviewed a prepared series of MR images (n = 25).
The participants were requested to identify image quality related errors, to
specify error-correction strategies and to score how confident they were in their
responses. Participants were then divided into experimental (n = 19) and control
cohorts (n = 16). The app was provided to the experimental cohort for 3 months;
after this period both cohorts re-reviewed the MR image datasets and repeated
their identification of image quality errors. RESULTS: The results showed a
statistically significant difference between control and experimental cohorts
relative to participants' pre- to post-test knowledge level. For the experimental
cohort, years of experience, qualification and type of hospital were not
associated with radiographer knowledge level and confidence in recognising the
presence of an image quality error, naming the error and specifying appropriate
correction strategies (p > 0.05). CONCLUSION: The study identified the potential
of the smartphone app as an effective educational tool to support MR
radiographers' knowledge in recognising and characterising MR image quality
errors. KEY POINTS: * A high level of knowledge to optimise MR image quality is
crucial. * Ongoing education in image quality optimisation is required. * The
potential role of app as an effective educational tool is identified.
PMID- 29949038
TI - Development of a Comprehensive Dataset of Hepatitis C Patients and Examination of
Disease Epidemiology in the United States, 2013-2016.
AB - INTRODUCTION: Chronic infection with hepatitis C virus (HCV) is a leading cause
of liver disease and infectious disease deaths. While recent and emerging
treatment options for HCV patients have enabled higher rates of sustained
virologic response (SVR), the demographic, clinical, geographic, and payer
characteristics of the estimated 3.4 million chronic HCV patients in the USA are
poorly understood. The goal of this study was to create a dataset describing the
current HCV patient landscape in the USA. METHODS: Data from two large national
laboratory companies representing the majority of US patients screened for HCV
antibody and/or tested for HCV RNA from 2013 through 2016 were organized into the
present study dataset. Age, gender, payer channel, 3-digit ZIP code and ordering
physician specialty, and 3-digit ZIP code information were available for all
patients. Among RNA-positive patients, additional clinical characteristics
included HCV genotype, fibrosis stage, renal function, and HIV status. Initiating
treatment and attaining cure were imputed using data-driven algorithms based on
successive RNA viral load measurements. RESULTS: The number of RNA-positive HCV
patients increased from 200,066 patients in 2013 to 469,550 in 2016. The
availability of clinical data measurements and rates of treatment initiation
increased over the study period, indicating improved care engagement for HCV
patients. Treatment and cure rates varied by age, disease severity, geographic
location, and payer channel. Sensitivity and specificity of the cure prediction
algorithms were consistently above 0.90, validating the robustness of the data
imputation approach. CONCLUSION: This is the largest, most comprehensive dataset
available to describe the current US HCV patient landscape. Our results highlight
that the epidemiology of HCV is evolving with an increasing number of patients
who are younger and have milder disease than described in previous years. Results
of this study should help guide efforts toward the elimination of HCV in this
country. Future work will focus on factors associated with varying treatment and
cure patterns and describing recent changes in the HCV patient landscape.
FUNDING: AbbVie. Plain language summary available for this article.
PMID- 29949039
TI - Advances in Clinical Cardiology 2017: A Summary of Key Clinical Trials.
AB - INTRODUCTION: Numerous important cardiology clinical trials have been published
or presented at major international meetings during 2017. This paper aims to
summarize these trials and place them in clinical context. METHODS: The authors
reviewed clinical trials presented at major cardiology conferences during 2017
including the American College of Cardiology, European Association for
Percutaneous Cardiovascular Interventions, European Society of Cardiology,
European Association for the Study of Diabetes, Transcatheter Cardiovascular
Therapeutics, and the American Heart Association. Selection criteria were trials
with a broad relevance to the cardiology community and those with potential to
change current practice. RESULTS: A total of 75 key cardiology clinical trials
were identified for inclusion. New interventional and structural cardiology data
include left main bifurcation treatment strategy, multivessel disease management
in cardiogenic shock, drug-eluting balloons for in-stent restenosis,
instantaneous wave-free physiological assessment, new-generation stents (COMBO,
Orsiro), transcatheter aortic valve implantation, and closure devices. New
preventative cardiology data include trials of liraglutide, empagliflozin, PCSK9
inhibitors (evolocumab and bococizumab), inclisiran, and anacetrapib.
Antiplatelet data include the role of uninterrupted aspirin therapy during non
cardiac surgery and dual antiplatelet therapy following coronary artery bypass
grafting. New data are also included from fields of heart failure (levosimendan,
spironolactone), atrial fibrillation (apixaban in DC cardioversion), cardiac
devices (closed loop stimulation pacing for neuromediated syncope), and
electrophysiology (catheter ablation for atrial fibrillation). CONCLUSION: This
paper presents a summary of key clinical cardiology trials during the past year
and should be of practical value to both clinicians and cardiology researchers.
PMID- 29949040
TI - Efficacy of Phonosurgery, Logopedic Voice Treatment and Vocal Pedagogy in Common
Voice Problems of Singers.
AB - INTRODUCTION: Functional and organic impairments of the singing voice are common
career-threatening problems of singers presenting in phoniatric and
laryngological departments. The objective was to evaluate the efficacy of
phonosurgery, logopedic voice treatment and vocal pedagogy in common organic and
functional voice problems of singers, including investigation of the recently
introduced parameter vocal extent measure (VEM). METHODS: In a prospective
clinical study, the analysis of treatment outcome in 76 singers [57 female, 19
male; 38 +/- 11 years (mean +/- SD)] was based on pre- and post-therapeutic voice
function diagnostics and videolaryngostroboscopy. Examination instruments
included auditory-perceptual voice assessment, voice range profile (VRP), the VEM
calculated from area and shape of the VRP, acoustic-aerodynamic analysis, and
patients' self-assessment (e.g., Singing Voice Handicap Index). RESULTS: While
28% of all singers (21/76) presented with functional dysphonia, 72% (55/76) were
diagnosed with organic vocal fold changes, of which marginal edema (n = 25),
nodules (n = 9), and polyps (n = 8) were the most common pathologic changes. Of
the 76 singers, 57% (43) received phonosurgery, 43% (33) had conservative
pedagogic (14) and logopedic (19) treatment. Three months post-therapeutically,
most parameters had significantly improved. The dysphonia severity index (DSI)
increased on average from 6.1 +/- 2.0 to 7.4 +/- 1.8 (p < 0.001), and the VEM
from 113 +/- 20 to 124 +/- 14 (p < 0.001). Both parameters correlated
significantly with each other (rs = 0.41). Phonosurgery had the largest impact on
the improvement of vocal function. Conservative therapies provided smaller
quantitative enhancements but also qualitative vocal restoration with recovered
artistic capabilities. CONCLUSIONS: Depending on individual medical indication,
phonosurgery, logopedic treatment and voice teaching are all effective,
objectively and subjectively satisfactory therapies to improve the impaired
singing voice. The use of VEM in singers with functional and organic dysphonia
objectifies and quantifies their vocal capacity as documented in the VRP.
Complementing the established DSI, VEM introduction into practical objective
voice diagnostics is appropriate and desirable especially for the treatment of
singers.
PMID- 29949041
TI - Safety and Tolerability of Combinations of Empagliflozin and Linagliptin in
Patients with Type 2 Diabetes: Pooled Data from Two Randomized Controlled Trials.
AB - INTRODUCTION: Two 52-week Phase III studies evaluated the efficacy and safety of
once-daily combinations of empagliflozin/linagliptin as monotherapy or add-on to
metformin in patients with type 2 diabetes (T2DM). The aim of this analysis was
to further assess the safety and tolerability of empagliflozin/linagliptin
compared with their individual components in patients with T2DM, using pooled
data from these trials. METHODS: A total of 1363 patients were treated with
empagliflozin 25 mg/linagliptin 5 mg (n = 273), empagliflozin 10 mg/linagliptin 5
mg (n = 272), empagliflozin 25 mg (n = 276), empagliflozin 10 mg (n = 275), or
linagliptin 5 mg (n = 267). Adverse events (AEs) were assessed descriptively in
patients who took >= 1 dose of study drug. RESULTS: Total exposure was 251, 255,
256, 249, and 243 patient-years in the empagliflozin 25 mg/linagliptin 5 mg,
empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg,
and linagliptin 5 mg groups, respectively. The proportion of patients with >= 1
AE was similar across groups (70.4-74.9%). The percentage of patients with
confirmed hypoglycemic AEs (plasma glucose <= 70 mg/dL and/or requiring
assistance) was low in all groups (1.1-2.2%); none required assistance. Events
consistent with urinary tract infection were reported in similar percentages of
patients in all groups (11.4-13.8%), and in a greater proportion of female than
male patients. Events consistent with genital infection were reported in higher
percentages of patients on empagliflozin/linagliptin or empagliflozin (4.0-6.5%)
than linagliptin 5 mg (2.6%), and in a greater proportion of females than males.
The risks of hypersensitivity reactions and events consistent with volume
depletion were low across treatment groups. CONCLUSION: Empagliflozin/linagliptin
as monotherapy or add-on to metformin for 52 weeks was well tolerated in patients
with T2DM, with safety profiles similar to individual components, including a low
risk of hypoglycemia. FUNDING: The Boehringer Ingelheim & Eli Lilly and Company
Diabetes Alliance. TRIAL REGISTRATION: ClinicalTrials.gov identifiers,
NCT01422876 & NCT01422876.
PMID- 29949042
TI - Unlicensed and Off-Label Medication Use in Pediatric and Neonatal Intensive Care
Units: No Change Over a Decade.
AB - INTRODUCTION: Many of the medications prescribed to children are off-label and/or
unlicensed because pharmacologic evaluations have not been performed in this age
group. METHODS: All drugs prescribed to patients admitted to the neonatal
intensive care units (NICU) (n = 134) and pediatric intensive care units (PICU)
(n = 56) during a 2-month observation period were recorded and classified
according to patient age, drug license status, indicated use, and typical dosing,
frequency and way of administration. Results were compared with prior data
collected in 2002, from the same units. RESULTS: In the NICU, among the 1064
prescriptions for 49 medications, 312 (29.2%) were licensed and 63 (5.9%)
unlicensed, and 693 (64.8%) were off-label use. For the neonates, 23.9% and 96.3%
received at least one unlicensed medication and one off-label medication,
respectively. While the difference in off-label use between the two time periods
was not statistically significant, unlicensed medications were less frequently
prescribed in 2016 (5.9 versus 16.6%, p = 0.001). Regarding the PICU, among the
388 prescriptions for 75 medications, 205 (52%) were licensed and 13 (3.4%)
unlicensed, and 170 (43.8%) were off-label. In contrast, in 2002, none of the
medications prescribed were unlicensed (p = 0.001). The number of off-label
medications (41%) and number of PICU patients receiving at least one
unlicensed/off-label medication in these two time periods (88.7% versus 90.5% for
2016 and 2002, respectively) were similar. CONCLUSIONS: The current study
confirms the high prevalence of unlicensed and off-label drug use in a PICU and
NICU setting. Compared with a similar study conducted in the same PICU in 2002,
despite regulatory efforts conducted in this area, the prevalence of unlicensed
medications was surprisingly higher.
PMID- 29949043
TI - Administration of Micronized Purified Flavonoid Fraction During Sclerotherapy of
Reticular Veins and Telangiectasias: Results of the National, Multicenter,
Observational Program VEIN ACT PROLONGED-C1.
AB - INTRODUCTION: Sclerotherapy is a common technique for the removal of intradermal
veins. This study examined the rationale for prescribing micronized purified
flavonoid fraction (MPFF) in clinical, etiological, anatomic, pathophysiologic
(CEAP) class C1 patients with dilated intradermal veins scheduled for
sclerotherapy. METHODS: In a national, multicenter, observational program,
physicians recruited CEAP C1s patients scheduled for sclerotherapy. The decision
to prescribe adjuvant MPFF (1000 mg/day for 6 weeks beginning 2 weeks before
sclerotherapy) was made according to usual practice. Disease severity and
treatment outcomes were assessed at baseline and 4 weeks post-sclerotherapy using
a visual analog scale (VAS) as well as quality-of-life (CIVIQ-14) and patient
satisfaction (Darvall) questionnaires. RESULTS: A total of 70 physicians
recruited 1150 patients: 1071 (93%) women, 79 (7%) men. Mean age (+/- SD) was
40.7 +/- 10.7 years (range 18-74) and mean body mass index was 23.6 +/- 3.3
kg/m2. Reticular veins were observed in 42.1% of patients and 57.9% had
telangiectasias. MPPF was prescribed to 905 patients (79%). Sclerotherapy was
associated with statistically significant decreases in mean VAS scores for leg
heaviness, pain, sensation of swelling, night cramps, and itching. For each
symptom, MPFF-treated patients showed a more pronounced improvement than those
undergoing sclerotherapy alone: mean VAS pain score with MPFF decreased from 1.90
+/- 2.30 to 0.30 +/- 0.62 versus 1.72 +/- 1.93 to 0.52 +/- 0.99 with
sclerotherapy alone; mean VAS leg heaviness score with MPFF decreased from 2.80
+/- 2.43 to 0.47 +/- 1.07 versus 2.38 +/- 2.23 to 0.76 +/- 0.85 with
sclerotherapy alone. Patient quality-of-life indicators improved with symptom
resolution, particularly pain, and for each indicator the observed improvement
was greater with MPFF. The outcomes of treatment exceeded patient expectations.
Fewer patients experienced sclerotherapy-induced hyperpigmentation with
adjunctive MPFF versus sclerotherapy alone (33.9% versus 41.2%, respectively, P =
0.034). No adverse events related to MPFF were observed. CONCLUSION: Resolution
of venous symptoms post-sclerotherapy was greater in patients treated with MPFF
compared with those undergoing sclerotherapy alone, supporting the rationale for
use of MPFF in patients undergoing sclerotherapy. FUNDING: Servier.
PMID- 29949044
TI - The Impact of Adding a Training Device to Familiar Counselling on Inhalation
Technique and Pulmonary Function of Asthmatics.
AB - INTRODUCTION: We have investigated the effect of adding a pressurized metered
dose inhaler (pMDI) training device to verbal counselling on pulmonary function
and inhalation technique. METHODS: A total of 304 adult asthmatic subjects (> 18
years old) were enrolled in a 3-month study of assessment and education. They
were divided into an investigation group (Trainhaler plus Flo-Tone and verbal
counselling, n = 261, mean age 49.2 years) and a control group (verbal
counselling only, n = 43, mean age 48.7 years). Pulmonary function and inhalation
technique were evaluated, mistakes noted, and the correct technique advised at
three consecutive monthly visits. Visits also included verbal pMDI counselling
(both groups) and training device coaching (investigation group). RESULTS: By
visit 2, the mean number of technique errors decreased significantly (p < 0.05)
in both groups (investigation group p < 0.001). The investigation group
demonstrated a marked decrease in the frequency of the critical error of
maintaining a slow inhalation rate until the lungs are full-a technique difficult
to learn via verbal counselling alone. The improvement in pulmonary function was
significant from the second clinic visit in the investigation group (p < 0.05)
and from the third visit in both groups (p < 0.001). CONCLUSIONS: Use of a
training device combined with verbal counselling improved inhalation technique.
An earlier, significant improvement was also noted in pulmonary function.
PMID- 29949045
TI - Rapid and Consistent Improvements in Morning PEF in Patients with Severe
Eosinophilic Asthma Treated with Mepolizumab.
AB - INTRODUCTION: Previous studies showed that mepolizumab significantly reduces
exacerbations and oral corticosteroid use in patients with severe eosinophilic
asthma. However, early studies reported inconsistent effects on lung function.
This study specifically assessed the onset of clinical effect and the
relationship of baseline blood eosinophil count of mepolizumab 100 mg
subcutaneous (SC) administration on morning peak expiratory flow (AM PEF).
METHODS: Post hoc analysis of data from two randomized, double-blind, placebo
controlled studies (MENSA, NCT01691521; MUSCA, NCT02281318) of 4-weekly
mepolizumab 100 mg versus placebo in patients with severe eosinophilic asthma.
Individual study results were generated using a mixed model repeated measures
model controlling for multiple covariates and were combined using a fixed effects
meta-analysis via inverse-variance weighting. RESULTS: Significant improvements
in AM PEF after the first dose of mepolizumab 100 mg SC vs. placebo were seen as
early as week 1 and continued to improve further with subsequent doses. The mean
change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the
placebo group, p < 0.001. When the population was stratified by blood eosinophil
thresholds the mean difference from placebo was 24 L/min (>= 150 cells/uL), 27
L/min (>= 300 cells/uL), and 34 L/min (>= 500 cells/uL), p < 0.001 for all
subgroups. The < 150 cells/uL (>= 300 cells/uL in the previous year) group
increased 13 L/min, while both 150 to < 300 cells/uL and 300 to < 500 cells/uL
ranges demonstrated comparable changes (19 L/min and 17 L/min), respectively.
CONCLUSION: Our analysis has shown early and consistent improvements in lung
function measured by AM PEF using the study enrollment criterion of >= 150
eosinophils/uL. We also identified a relationship between baseline blood
eosinophils and improvements in AM PEF with mepolizumab in patients with severe
eosinophilic asthma. FUNDING: GlaxoSmithKline (study ID 208091).
PMID- 29949046
TI - Phytomedicines in Acute Rhinosinusitis: A Prospective, Non-interventional
Parallel-Group Trial.
AB - INTRODUCTION: The objective of this prospective, multicenter, parallel-group, non
interventional clinical trial (NIT) was to characterize the effectiveness of a
treatment with the phytomedicines ELOM-080 and BNO 1016 in patients with acute
rhinosinusitis (ARS). METHODS: A total of 228 patients suffering from ARS took
part in this NIT and were treated for a maximum of 14 days with either BNO 1016
or ELOM-080. Focus was on improvement of rhinosinusitis-associated
pain/discomfort and nasal congestion in real-life conditions of primary care
setting, as assessed by numeric and verbal rating scale, and five-point Likert
scale. RESULTS: The course of the key ARS symptom facial pain demonstrated a
faster recovery in patients with ELOM-080, when compared to BNO 1016. ELOM-080
tended to be superior for several ancillary criteria and induced significantly
higher patient satisfaction with regard to the improvement of feeling of general
illness. Physicians assessed both products to be very effective and well
tolerated. Adverse drug reactions classified as gastrointestinal disorders
occurred in both groups to a comparable extent. CONCLUSION: This trial
demonstrated comparable effectiveness of a therapy of ARS with the phytomedicines
ELOM-080 and BNO 1016, although the treatment with ELOM-080 resulted in a more
rapid and more complete recovery in ARS key symptoms and tended to be superior
for several ancillary criteria. Both treatments were well tolerated. TRIAL
REGISTRATION NUMBER: NIS-6471. FUNDING: G. Pohl-Boskamp GmbH & Co. KG.
PMID- 29949047
TI - Comparative Efficacy of Treatments for Previously Treated Advanced or Metastatic
Non-Small-Cell Lung Cancer: A Network Meta-Analysis.
AB - INTRODUCTION: Due to the rarity of BRAF V600E mutation, no randomized study has
compared the combination targeted therapy dabrafenib + trametinib with other
second-line treatments for advanced or metastatic non-small-cell lung cancer
(NSCLC). A network meta-analysis (NMA) was conducted to assess the comparative
efficacy of treatments among patients with previously treated advanced or
metastatic NSCLC. METHODS: Randomized trials of dabrafenib + trametinib,
docetaxel, erlotinib, nintedanib + docetaxel, nivolumab, pemetrexed,
pembrolizumab, and best supportive care as second-line or above treatments for
advanced or metastatic NSCLC identified in a systematic literature review were
included in the NMA. Overall response rates (ORRs) and disease control rates
(DCRs) were compared using logit models; progression-free survival (PFS) and
overall survival (OS) were compared using fractional polynomial hazards models.
Dabrafenib + trametinib was linked into the evidence network through a matching
adjusted indirect comparison versus nivolumab. RESULTS: Ten trials met the
inclusion criteria and were included in the NMA. Dabrafenib + trametinib,
pembrolizumab, and nivolumab were associated with the highest odds of achieving
overall response (12.2, 1.2, and 0.7 times higher, respectively, compared with
docetaxel). Estimated DCR was higher for dabrafenib + trametinib, nintedanib +
docetaxel, and pemetrexed compared with other treatments. Patients treated with
dabrafenib + trametinib, nivolumab, and pembrolizumab had the lowest hazards of
disease progression or death during follow-up (72, 61, and 29% lower hazard of
progression at 6 months; 61, 48, and 46% lower hazard of death at 1 year,
respectively, compared with docetaxel). CONCLUSION: Dabrafenib + trametinib,
pembrolizumab, and nivolumab were associated with higher ORR and prolonged PFS
and OS compared with chemotherapy in previously treated advanced or metastatic
NSCLC. FUNDING: Novartis Pharmaceuticals Corporation.
PMID- 29949048
TI - Systematic Review and Meta-Analysis of the Prognostic Significance of Neutrophil
Lymphocyte Ratio (NLR) After R0 Gastrectomy for Cancer.
AB - PURPOSE: A meta-analysis was performed to evaluate the prognostic value of
neutrophil-lymphocyte ratio (NLR) in patients undergoing potentially curative
gastrectomy for cancer (GC). METHODS: Thomson Reuters Web of Science, Ovid
MEDLINE(R) and PUBMED databases were searched for relevant articles using search
terms neutrophil-lymphocyte ratio (NLR), GC and survival. Articles reporting
overall survival (OS), cancer-specific survival and disease-free survival (DFS),
in patients undergoing R0 gastrectomy, were studied. RESULTS: Articles numbering
365 were identified during the preliminary search, and 10 containing 4164
patients were included in the final review. Most patients were > 60 years of age,
male (67%) and 2239 (53.8%) had pT3 disease. The number of NLR dichotomization
thresholds reported numbered 7, with 2.00 and 3.00 (n = 2) the most common. NLR
was associated with poor survival in eight studies with hazard ratios ranging
from 1.54 (95% confidence interval (CI) 1.26-1.89) to 2.99 (1.99-4.49). Pooled
odds ratio (OR) for OS was 2.31 (1.40-3.83, p = 0.001) and for DFS 2.72 (1.14
6.54, p = 0.020). Four studies presented T-stage data, OR 1.62 (1.33-1.96, p <
0.001). CONCLUSION: NLR is an important prognostic indicator associated with both
OS and DFS after R0 resection of GC, but the critical level is equivocal.
PMID- 29949049
TI - Targeting glucose transport and the NAD pathway in tumor cells with STF-31: a re
evaluation.
AB - BACKGROUND: Targeting glucose metabolism is a promising way to interfere with
tumor cell proliferation and survival. However, controversy exists about the
specificity of some glucose metabolism targeting anticancer drugs. Especially the
potency of STF-31 has been debated. Here, we aimed to assess the impact of the
glucose transporter (GLUT) inhibitors fasentin and WZB117, and the nicotinamide
phosphoribosyltransferase (NAMPT) inhibitors GMX1778 and STF-31 on tumor cell
proliferation and survival, as well as on glucose uptake. METHODS: Tumor-derived
A172 (glioblastoma), BHY (oral squamous cell carcinoma), HeLa (cervix
adenocarcinoma), HN (head neck cancer), HT-29 (colon carcinoma) and MG-63
(osteosarcoma) cells were treated with fasentin, WZB117, GMX1778 and STF-31.
Proliferation rates and cell viabilities were assessed using XTT, crystal violet
and LDH assays. mRNA and protein expression of GLUT1 and NAPRT were assessed
using qPCR and Western blotting, respectively. The effects of inhibiting
compounds on glucose uptake were measured using [18F]-fluoro-deoxyglucose uptake
experiments. RESULTS: Stimulation of tumor-derived cells with the different
inhibitors tested revealed a complex pattern, whereby proliferation inhibiting
and survival reducing concentrations varied in [18F]-fluoro-deoxyglucose uptake
experiments more than one order of magnitude among the different cells tested. We
found that the effects of GMX1778 and STF-31 could be partially abolished by (i)
nicotinic acid (NA) only in nicotinic acid phosphoribosyltransferase (NAPRT)
expressing cells and (ii) nicotinamide mononucleotide (NMN) in all cells tested,
supporting the classification of these compounds as NAMPT inhibitors. In short
time [18F]-fluoro-deoxyglucose uptake experiments the application of WZB-117 was
found to lead to an almost complete uptake inhibition in all cells tested,
whereas the effect of fasentin was found to be cell type dependent with a maximum
value of ~35% in A172, BHY, HeLa and HT-29 cells. We also found that STF-31
inhibited glucose uptake in all cells tested in a range of 25-50%. These data
support the classification of STF-31 as a GLUT inhibitor. CONCLUSIONS: Our data
reveal a dual mode of action of STF-31, serving either as a NAMPT or as a GLUT
inhibitor, whereby the latter seems to be apparent only at higher STF-31
concentrations. The molecular basis of such a dual function and its appearance in
compounds previously designated as NAMPT-specific inhibitors requires further
investigation.
PMID- 29949050
TI - Mesenchymal marker and LGR5 expression levels in circulating tumor cells
correlate with colorectal cancer prognosis.
AB - PURPOSE: The presence of circulating tumor cells (CTCs) has been found to
correlate with colorectal cancer (CRC) prognosis, whereas epithelial-mesenchymal
transition (EMT) in CTCs has been found to be associated with CRC metastasis.
LGR5 is a known target of Wnt signaling and plays an important role in CRC
development. The aim of this study was to assess the clinical relevance of EMT
and LGR5 expression in CTCs from CRC patients. METHODS: Sixty-six CRC patients
were included in this study. The detection and expression of EMT phenotypes in
CTCs from these patients were assessed using CanPatrolTM CTC enrichment and mRNA
in situ hybridization (ISH), respectively. LGR5 expression in the CTCs was
assessed using mRNA ISH. RESULTS: CTCs were detected in 86.4% (57/66) of the CRC
patients included. Both the numbers of total CTCs and of CTCs displaying a
mesenchymal phenotype (M+ CTCs) were found to significantly correlate with
advanced disease stages and the occurrence of metastasis (p < 0.05). An adjusted
multivariate analysis also indicated that the number of M+ CTCs significantly
correlated with the occurrence of metastasis (p = 0.031). Additionally, we found
that a high LGR5 expression level significantly correlated with the occurrence of
metastasis (p < 0.05). We also found that the presence of >= 6 CTCs or >= 3 M+
CTCs per 5 ml blood significantly correlated with disease progression (p < 0.05).
Patients with >= 6 CTCs or >= 3 M+ CTCs per 5 ml blood were found to exhibit
poorer progression-free survival (PFS) and overall survival (OS) rates (p < 0.05
in all cases). Using Cox regression analyses, we found that only total CTC
numbers remained as independent prognostic factors for a worse PFS (p = 0.043).
CONCLUSIONS: From our data we conclude that CTC numbers and EMT phenotypes may
serve as prognostic markers for disease progression and metastasis in CRC
patients. In addition, we conclude that LGR5 expression in CTCs may serve as a
marker for CRC metastasis.
PMID- 29949052
TI - Effect of In-Class vs Online Education on Sexual Health Communication Skills in
First-Year Medical Students: a Pilot Study.
AB - OBJECTIVE: Online education is effective for knowledge acquisition, but its
effect on clinical skill development is not well characterized. We aimed to
compare communication skills of 50 first-year medical students who learned to
assess and treat patients through an online learning module vs an in-class
lecture. METHODS: Twenty-six students were randomized to learn about
antidepressant-induced sexual dysfunction in class and 24 learned the same
content through an online module. Students were individually observed conducting
an interview with a standardized patient with antidepressant-induced sexual
dysfunction. Students were assessed by faculty raters blinded to the student's
learning mode. Standardized patients were asked about their willingness to have
the student as their physician. RESULTS: More students who learned in class vs
online demonstrated appropriate verbal empathy (18 [69%] vs 8 [33%]; P = 0.01),
defined as completing each task in the "verbal empathy" assessment domain, as
measured by a faculty rater. Other assessed variables were not significantly
different. Standardized patients' willingness (vs unwillingness; P = 0.01) to
have the student as their physician was associated with the demonstration (by
faculty appraisal) of a number of basic skills: using open-ended questions,
asking one question at a time, using gender-neutral terminology when asking about
the patient's relationship, and using appropriate sexual-health terminology.
CONCLUSIONS: This study, although limited by a single-site design and the small
number of participants, offers preliminary evidence that, if confirmed, may
suggest that in-class learning from a psychiatrist (vs from an online module) is
associated with greater verbal empathy in the assessment of SSRI-related sexual
dysfunction.
PMID- 29949051
TI - Stromal collagen type VI associates with features of malignancy and predicts poor
prognosis in salivary gland cancer.
AB - PURPOSE: Collagen Type VI (COLVI) is an extracellular matrix protein that is
upregulated in various solid tumours during tumour progression and has been shown
to stimulate proliferation, suppress apoptosis and promote invasion and
metastasis. It has also been described as a mediator of chemotherapy resistance
and as a therapeutic target in preclinical cancer models. Here, we aimed to
analyse the prognostic role of COLVI in salivary gland cancer (SGC). METHODS:
Stromal COLVI protein expression was assessed in primary SGC specimens of 91
patients using immunohistochemistry (IHC). The IHC expression patterns obtained
were subsequently correlated with various survival and clinicopathological
features, including Ki-67 and p53 expression. RESULTS: We found that COLVI was
expressed in all SGC specimens. High expression was found to be associated with
features of malignancy such as high histologic grades, advanced and invasive T
stages and metastatic lymph node involvement (p < 0.05 for all variables). COLVI
expression was also found to correlate with both Ki-67 and p53 expression (p <
0.01). We found that high COLVI expression predicted a significantly inferior 5
year overall survival (38.3%, 55.1% and 93.8%; p = 0.002) and remained a
significant predictor of prognosis in a multivariate Cox regression analysis
(hazard ratio, 2.62; 95% confidence interval, 1.22-5.61; p = 0.013). In all low
risk subgroups COLVI expression identified patients with an adverse outcome.
Patients receiving adjuvant radiotherapy had a poor survival when expressing high
levels of COLVI. CONCLUSIONS: Our data indicate that stromal COLVI expression
associates with key features of malignancy, represents a novel independent
prognostic factor and may affect response to radiotherapy in SGC. Although our
results warrant validation in an independent cohort, assessing stromal COLVI
expression may be suitable for future diagnostic and therapeutic decision making
in patients with SGC.
PMID- 29949053
TI - Current Technology in Advancing Medical Education: Perspectives for Learning and
Providing Care.
PMID- 29949054
TI - Professionalism and Technology: Competencies Across the Tele-Behavioral Health
and E-Behavioral Health Spectrum.
PMID- 29949055
TI - Identification and High-Resolution Imaging of alpha-Tocopherol from Human Cells
to Whole Animals by TOF-SIMS Tandem Mass Spectrometry.
AB - A unique method for identification of biomolecular components in different
biological specimens, while preserving the capability for high speed 2D and 3D
molecular imaging, is employed to investigate cellular response to oxidative
stress. The employed method enables observing the distribution of the antioxidant
alpha-tocopherol and other molecules in cellular structures via time-of-flight
secondary ion mass spectrometry (TOF-SIMS (MS1)) imaging in parallel with tandem
mass spectrometry (MS2) imaging, collected simultaneously. The described method
is employed to examine a network formed by neuronal cells differentiated from
human induced pluripotent stem cells (iPSCs), a model for investigating human
neurons in vitro. The antioxidant alpha-tocopherol is identified in situ within
different cellular layers utilizing a 3D TOF-SIMS tandem MS imaging analysis. As
oxidative stress also plays an important role in mediating inflammation, the
study was expanded to whole body tissue sections of M. marinum-infected
zebrafish, a model organism for tuberculosis. The TOF-SIMS tandem MS imaging
results reveal an increased presence of alpha-tocopherol in response to the
pathogen. Graphical Abstract ?.
PMID- 29949056
TI - Differentiating Positional Isomers of Nucleoside Modifications by Higher-Energy
Collisional Dissociation Mass Spectrometry (HCD MS).
AB - The analytical identification of positional isomers (e.g., 3-, N4-, 5
methylcytidine) within the > 160 different post-transcriptional modifications
found in RNA can be challenging. Conventional liquid chromatography coupled with
tandem mass spectrometry (LC-MS/MS) approaches rely on chromatographic separation
for accurate identification because the collision-induced dissociation (CID) mass
spectra of these isomers nearly exclusively yield identical nucleobase ions
(BH2+) from the same molecular ion (MH+). Here, we have explored higher-energy
collisional dissociation (HCD) as an alternative fragmentation technique to
generate more informative product ions that can be used to differentiate
positional isomers. LC-MS/MS of modified nucleosides characterized using HCD led
to the creation of structure- and HCD energy-specific fragmentation patterns that
generated unique fingerprints, which can be used to identify individual
positional isomers even when they cannot be separated chromatographically. While
particularly useful for identifying positional isomers, the fingerprinting
capabilities enabled by HCD also offer the potential to generate HPLC-independent
spectral libraries for the rapid analysis of modified ribonucleosides. Graphical
Abstract ?.
PMID- 29949057
TI - Radical Anions of Oxidized vs. Reduced Oxytocin: Influence of Disulfide Bridges
on CID and Vacuum UV Photo-Fragmentation.
AB - The nonapeptide oxytocin (OT) is used as a model sulfur-containing peptide to
study the damage induced by vacuum UV (VUV) radiations. In particular, the effect
of the presence (or absence in reduced OT) of oxytocin's internal disulfide
bridge is evaluated in terms of photo-fragmentation yield and nature of the photo
fragments. Intact, as well as reduced, OT is studied as dianions and radical
anions. Radical anions are prepared and photo-fragmented in two-color experiments
(UV + VUV) in a linear ion trap. VUV photo-fragmentation patterns are analyzed
and compared, and radical-induced mechanisms are proposed. The effect of VUV is
principally to ionize but secondary fragmentation is also observed. This
secondary fragmentation seems to be considerably enabled by the initial position
of the radical on the molecule. In particular, the possibility to form a radical
on free cysteines seems to increase the susceptibility to VUV fragmentation.
Interestingly, disulfide bridges, which are fundamental for protein structure,
could also be responsible for an increased resistance to ionizing radiations.
Graphical Abstract.
PMID- 29949058
TI - Gas Chromatography-Tandem Mass Spectrometry of Lignin Pyrolyzates with Dopant
Assisted Atmospheric Pressure Chemical Ionization and Molecular Structure Search
with CSI:FingerID.
AB - Dopant-assisted atmospheric pressure chemical ionization (dAPCI) is a soft
ionization method rarely used for gas chromatography-mass spectrometry (GC-MS).
The current study combines GC-dAPCI with tandem mass spectrometry (MS/MS) for
analysis of a complex mixture such as lignin pyrolysis analysis. To identify the
structures of volatile lignin pyrolysis products, collision-induced dissociation
(CID) MS/MS using a quadrupole time-of-flight mass spectrometer (QTOFMS) and
pseudo MS/MS through in-source collision-induced dissociation (ISCID) using a
single stage TOFMS are utilized. To overcome the lack of MS/MS database, Compound
Structure Identification (CSI):FingerID is used to interpret CID spectra and
predict best matched structures from PubChem library. With this approach, a total
of 59 compounds were positively identified in comparison to only 22 in NIST
database search of GC-EI-MS dataset. This study demonstrates the effectiveness of
GC-dAPCI-MS/MS to overcome the limitations of traditional GC-EI-MS analysis when
EI-MS database is not sufficient. Graphical Abstract ?.
PMID- 29949059
TI - Oligomerisation of Synaptobrevin-2 Studied by Native Mass Spectrometry and
Chemical Cross-Linking.
AB - Synaptobrevin-2 is a key player in signal transmission in neurons. It forms,
together with SNAP25 and Syntaxin-1A, the neuronal soluble N-ethylmaleimide
sensitive factor attachment protein receptor (SNARE) complex and mediates
exocytosis of synaptic vesicles with the pre-synaptic membrane. While
Synaptobrevin-2 is part of a four-helix bundle in this SNARE complex, it is
natively unstructured in the absence of lipids or other SNARE proteins. Partially
folded segments, presumably SNARE complex formation intermediates, as well as
formation of Synaptobrevin-2 dimers and oligomers, were identified in previous
studies. Here, we employ three Synaptobrevin-2 variants-the full-length protein
Syb(1-116), the soluble, cytosolic variant Syb(1-96) as well as a shorter version
Syb(49-96) containing structured segments but omitting a trigger site for SNARE
complex formation-to study oligomerisation in the absence of interaction partners
or when incorporated into the lipid bilayer of liposomes. Combining native mass
spectrometry with chemical cross-linking, we find that the truncated versions
show increased oligomerisation. Our findings from both techniques agree well and
confirm the presence of oligomers in solution while membrane-bound Synaptobrevin
2 is mostly monomeric. Using ion mobility mass spectrometry, we could further
show that lower charge states of Syb(49-96) oligomers, which most likely
represent solution structures, follow an isotropic growth curve suggesting that
they are intrinsically disordered. From a technical point of view, we show that
the combination of native ion mobility mass spectrometry with chemical cross
linking is well-suited for the analysis of protein homo-oligomers. Graphical
Abstract ?.
PMID- 29949060
TI - Coaxial Electrospray Ionization for the Study of Rapid In-source Chemistry.
AB - Coaxial electrospray has been used effectively for several dual-emitter
applications, but has not been utilized for the study of rapid in-source
chemistry. In this paper, we report the fabrication of a coaxial, micro-volume
dual-emitter through the modification of a manufacturer's standard electrospray
probe. This modification creates rapid mixing inside the Taylor cone and the
ability to manipulate fast reactions using a variety of solvents and analytes. We
demonstrate its potential as a low-cost, dual-emitter assembly for diverse
applications through three examples: relative ionization in a biphasic
electrospray, hydrogen-deuterium exchange, and protein supercharging. Graphical
Abstract.
PMID- 29949061
TI - Initial Protein Unfolding Events in Ubiquitin, Cytochrome c and Myoglobin Are
Revealed with the Use of 213 nm UVPD Coupled to IM-MS.
AB - The initial stages of protein unfolding may reflect the stability of the entire
fold and can also reveal which parts of a protein can be perturbed, without
restructuring the rest. In this work, we couple UVPD with activated ion mobility
mass spectrometry to measure how three model proteins start to unfold. Ubiquitin,
cytochrome c and myoglobin ions produced via nESI from salty solutions are
subjected to UV irradiation pre-mobility separation; experiments are conducted
with a range of source conditions which alter the conformation of the precursor
ion as shown by the drift time profiles. For all three proteins, the compact
structures result in less fragmentation than more extended structures which
emerge following progressive in-source activation. Cleavage sites are found to
differ between conformational ensembles, for example, for the dominant charge
state of cytochrome c [M + 7H]7+, cleavage at Phe10, Thr19 and Val20 was only
observed in activating conditions whilst cleavage at Ala43 is dramatically
enhanced. Mapping the photo-cleaved fragments onto crystallographic structures
provides insight into the local structural changes that occur as protein
unfolding progresses, which is coupled to global restructuring observed in the
drift time profiles. Graphical Abstract.
PMID- 29949062
TI - Correction to: The Proceedings of the 95th Annual Meeting of the Physiological
Society of Japan March 28-30, Takamatsu, Kagawa, Japan.
AB - In the original publication of the article, there are following misprints in the
numbering of the planned symposia.
PMID- 29949063
TI - Mechanism of luminal ATP activated chloride secretion in a polarized epithelium.
AB - There are both secretory and absorptive pathways working in tandem to support
ionic movement driving fluid secretion across epithelia. The mechanisms exerting
control of fluid secretion in the oviduct is yet to be fully determined. This
study explored the role of apical or luminal extracellular ATP (ATPe)-stimulated
ion transport in an oviduct epithelium model, using the Ussing chamber short
circuit current (Isc) technique. Basal Isc in oviduct epithelium in response to
apical ATPe comprises both chloride secretion and sodium absorption and has
distinct temporal phases. A rapid transient peak followed by a sustained small
increase above baseline. Both phases of the apical ATPe Isc response are
sensitive to anion (HCO3-, Cl-) and cation (Na+) replacement. Additionally, the
role of apical chloride channels, basolateral potassium channels and
intracellular calcium in supporting the peak Isc current was confirmed. The role
of ATP breakdown to adenosine resulting in the activation of P2 receptors was
supported by examining the effects of non-hydrolyzable forms of ATP. A P2YR2
potency profile of ATP = UTP > ADP was generated for the apical membrane,
suggesting the involvement of the P2YR2 subtype of purinoceptor. A P2X potency
profile of ATP = 2MeSATP > alpha,beta-meATP > BzATP was also generated for the
apical membrane. In conclusion, these results provide strong evidence that
purinergic activation of apical P2YR2 promotes chloride secretion and is thus an
important factor in fluid formation by the oviduct.
PMID- 29949064
TI - Conducting a Time Trade-Off Study Alongside a Clinical Trial: A Case Study and
Recommendations.
AB - Time trade-off (TTO) is an established method in health economics to elicit and
value individuals' preferences for different health states. These preferences are
expressed in the form of health-state utilities that are typically used to
measure health-related quality of life and calculate quality-adjusted life-years
in an economic evaluation. The TTO approach to directly elicit health-state
utilities is particularly valuable when generic instruments (e.g. EQ-5D) may not
fully capture changes in utility in a clinical trial. However, there is limited
guidance on how a TTO study should be conducted alongside a clinical trial
despite it being a valuable tool. We present an account of the design and
development of a TTO study within a clinical trial as a case study. We describe
the development of materials needed for the TTO interviews, the piloting of the
TTO materials and interview process, and recommendations for future TTO studies.
This paper provides a practical guide and reference for future applications of
the TTO method alongside a clinical trial.
PMID- 29949065
TI - Parents' views of genetic testing and treatment of familial hypercholesterolemia
in children: a qualitative study.
AB - Familial hypercholesterolemia (FH) is a serious inherited disorder, which greatly
increases individuals' risk of cardiovascular disease (CVD) in adult life.
However, medical treatment and lifestyle adjustments can fully restore life
expectancy. Whilst European guidance advises that where there is a known family
mutation genetic testing is undertaken in early childhood, the majority of the at
risk population remain untested and undiagnosed. To date, only a small number of
studies have explored parents' and children's experiences of testing and
treatment for FH, and little is known about interactions between health
professionals, parents, and children in clinic settings. In this study, in-depth
interviews were undertaken with parents who had attended a genetics and/or lipid
clinic for FH with their children (n = 17). A thematic analysis revealed four
main themes: undertaking early prevention, postponing treatment, parental
concerns, and the importance of the wider family context. The majority of parents
supported genetic testing for FH in childhood. However, although some were very
supportive of following early treatment recommendations, others expressed
reluctance. Importantly, some parents were concerned that inappropriate
information had been shared with their children and wished that more time had
been given to discuss how, when, and what to tell in advance. Future research is
needed to explore the long-term outcomes for children who undertake genetic
testing and early treatment for FH and to trial interventions to improve the
engagement, follow-up, and support of children who are at risk, or diagnosed,
with this disorder.
PMID- 29949066
TI - Ethics in genetic counselling.
AB - Difficult ethical issues arise for patients and professionals in medical
genetics, and often relate to the patient's family or their social context.
Tackling these issues requires sensitivity to nuances of communication and a
commitment to clarity and consistency. It also benefits from an awareness of
different approaches to ethical theory. Many of the ethical problems encountered
in genetics relate to tensions between the wishes or interests of different
people, sometimes even people who do not (yet) exist or exist as embryos, either
in an established pregnancy or in vitro. Concern for the long-term welfare of a
child or young person, or possible future children, or for other members of the
family, may lead to tensions felt by the patient (client) in genetic counselling.
Differences in perspective may also arise between the patient and professional
when the latter recommends disclosure of information to relatives and the patient
finds that too difficult, or when the professional considers the genetic testing
of a child, sought by parents, to be inappropriate. The expectations of a
patient's community may also lead to the differences in perspective between
patient and counsellor. Recent developments of genetic technology permit genome
wide investigations. These have generated additional and more complex data that
amplify and exacerbate some pre-existing ethical problems, including those
presented by incidental (additional sought and secondary) findings and the
recognition of variants currently of uncertain significance, so that reports of
genomic investigations may often be provisional rather than definitive.
Experience is being gained with these problems but substantial challenges are
likely to persist in the long term.
PMID- 29949067
TI - Genetics and ethics.
PMID- 29949068
TI - Genetic counseling in an indigenous Filipino community with a high prevalence of
A2ML1-related otitis media.
AB - In this report, we describe the knowledge and beliefs on causes and management of
otitis media of an indigenous Filipino community with a high prevalence of otitis
media that is associated with an A2ML1 variant. Community lectures and individual
genetic counseling were provided as intervention. Knowledge, beliefs, and health
care-seeking behavior pertaining to otitis media were assessed pre- and post
genetic counseling. Twenty-five heads of households were interviewed. Beliefs
regarding etiology of ear discharge varied widely, with swimming in the sea as
the most commonly cited cause of ear discharge. During the post-counseling
session, poor personal hygiene, dirty environment, and familial inheritance were
mentioned as risk factors for otitis media or ear discharge. Knowledge about the
genotypes for the A2ML1 variant and otitis media diagnoses within the household
influenced beliefs on the role of hygiene and genetic susceptibility to otitis
media and attitudes towards health care-seeking behavior. Genetic counseling was
associated with variable improvement in knowledge on otitis media and in their
understanding of genetic susceptibility to otitis media due to the A2ML1 variant.
Language barriers, literacy level, cultural factors, and the complex nature of
genetic information made genetic counseling in the particular population a
challenge. Insights drawn from this experience recommend follow-up visits in the
community.
PMID- 29949069
TI - Sensory experience ratings for 5,500 Spanish words.
AB - Sensory experience rating (SER) is a recently developed subjective lexical index
that reflects the extent to which a word evokes a sensory and/or perceptual
experience in a reader (Juhasz & Yap, 2013; Juhasz, Yap, Dicke, Taylor, &
Gullick, 2011). In the present study, SERs for a set of 5,500 Spanish words were
collected, which makes this the largest set of norms for SER in the Spanish
language to date. Additionally, with the aim of further exploring the
implications of this new indicator and its relations with other psycholinguistic
variables, a variety of correlational and regression analyses are provided. The
results showed that SERs significantly correlated with imageability, age of
acquisition, and a number of variables related to perception and emotion. In
addition, SERs predicted a significant amount of variance in lexical decision
times when other variables were controlled.
PMID- 29949070
TI - An assessment of touchscreens for testing primate food preferences and
valuations.
AB - Typically, animals' food preferences are tested manually, which can be both time
consuming and vulnerable to experimenter biases. Given the utility of
ascertaining animals' food preferences for research and husbandry protocols,
developing a quick, reliable, and flexible paradigm would be valuable for
expediting many research protocols. Therefore, we evaluated the efficacy of using
a touchscreen interface to test nonhuman primates' food preferences and
valuations, adapting previously validated manual methods. We tested a nonhuman
primate subject with four foods (carrot, cucumber, grape, and turnip). Preference
testing followed a pairwise forced choice protocol with pairs of food images
presented on a touchscreen: The subject was rewarded with whichever food was
selected. All six possible pairwise combinations were presented, with 90 trials
per pairing. Second, we measured how hard the subject was willing to work to
obtain each of the four foods, allowing us to generate demand curves. For this
phase, a single image of a food item was presented on the touchscreen that the
subject had to select in order to receive the food, and the number of selections
required increased following a quarter-log scale, with ten trials per cost level
(1, 2, 3, 6, 10, and 18). These methods allowed us to ascertain the subject's
relative preferences and valuations of the four foods. The success of this
touchscreen protocol for testing the subject's food preferences, from both a
practical and a theoretical standpoint, suggests that the protocol should be
further validated with other foods with this subject, with other subjects, and
with other test items.
PMID- 29949071
TI - On the importance of avoiding shortcuts in applying cognitive models to
hierarchical data.
AB - Psychological experiments often yield data that are hierarchically structured. A
number of popular shortcut strategies in cognitive modeling do not properly
accommodate this structure and can result in biased conclusions. To gauge the
severity of these biases, we conducted a simulation study for a two-group
experiment. We first considered a modeling strategy that ignores the hierarchical
data structure. In line with theoretical results, our simulations showed that
Bayesian and frequentist methods that rely on this strategy are biased towards
the null hypothesis. Secondly, we considered a modeling strategy that takes a two
step approach by first obtaining participant-level estimates from a hierarchical
cognitive model and subsequently using these estimates in a follow-up statistical
test. Methods that rely on this strategy are biased towards the alternative
hypothesis. Only hierarchical models of the multilevel data lead to correct
conclusions. Our results are particularly relevant for the use of hierarchical
Bayesian parameter estimates in cognitive modeling.
PMID- 29949072
TI - Conjoint psychometric field estimation for bilateral audiometry.
AB - Behavioral testing in perceptual or cognitive domains requires querying a subject
multiple times in order to quantify his or her ability in the corresponding
domain. These queries must be conducted sequentially, and any additional testing
domains are also typically tested sequentially, such as with distinct tests
comprising a test battery. As a result, existing behavioral tests are often
lengthy and do not offer comprehensive evaluation. The use of active machine
learning kernel methods for behavioral assessment provides extremely flexible yet
efficient estimation tools to more thoroughly investigate perceptual or cognitive
processes without incurring the penalty of excessive testing time. Audiometry
represents perhaps the simplest test case to demonstrate the utility of these
techniques. In pure-tone audiometry, hearing is assessed in the two-dimensional
input space of frequency and intensity, and the test is repeated for both ears.
Although an individual's ears are not linked physiologically, they share many
features in common that lead to correlations suitable for exploitation in
testing. The bilateral audiogram estimates hearing thresholds in both ears
simultaneously by conjoining their separate input domains into a single search
space, which can be evaluated efficiently with modern machine-learning methods.
The result is the introduction of the first conjoint psychometric function
estimation procedure, which consistently delivers accurate results in
significantly less time than sequential disjoint estimators.
PMID- 29949073
TI - Using Hamiltonian Monte Carlo to estimate the log-linear cognitive diagnosis
model via Stan.
AB - The Bayesian literature has shown that the Hamiltonian Monte Carlo (HMC)
algorithm is powerful and efficient for statistical model estimation, especially
for complicated models. Stan, a software program built upon HMC, has been
introduced as a means of psychometric modeling estimation. However, there are no
systemic guidelines for implementing Stan with the log-linear cognitive diagnosis
model (LCDM), which is the saturated version of many cognitive diagnostic model
(CDM) variants. This article bridges the gap between Stan application and
Bayesian LCDM estimation: Both the modeling procedures and Stan code are
demonstrated in detail, such that this strategy can be extended to other CDMs
straightforwardly.
PMID- 29949074
TI - Characterization and phylogenetic analysis of the complete mitogenome of a rare
cavefish, Sinocyclocheilus multipunctatus (Cypriniformes: Cyprinidae).
AB - The genus Sinocyclocheilus is a representative group of cave creatures. However,
genetic studies on Sinocyclocheilus are rare. The primary objective of this study
was to explore the structure and feature of the complete mitochondrial genome of
S. multipunctatus, and reconstruct the mitogenomic phylogeny of Sinocyclocheilus.
The mitochondrial DNA of S. multipunctatus was amplified by overlapping PCR
fragments. The mitogenome was assembled by the SeqMan and annotated using
MitoAnnotator. The phylogenetic tree was established using the Bayesian inference
and Maximum likelihood methods. The mitogenome of S. multipunctatus is a typical
circular molecule of 16,586 bp with base composition A (31.25%), T (25.90%), G
(16.35%), and C (26.50%), and consists of 13 protein-coding genes (PCGs), 22
transfer RNAs (tRNAs) genes, two ribosomal RNAs, and a 931 bp control region.
Phylogenetic analysis reveals two clades in the Sinocyclocheilus with robust
support. S. multipunctatus is close to a newly discovered cavefish, S.
ronganensis. We obtained and described the complete mitogenome of S.
multipunctatus, and investigated its phylogenetic status, which may provide a
valuable resource for future phylogenetic analyses and population genetic studies
in Sinocyclocheilus.
PMID- 29949075
TI - Functional conservation of Arabidopsis LNG1 in tobacco relating to leaf shape
change by increasing longitudinal cell elongation by overexpression.
AB - The LONGIFOLIA1 (LNG1) gene of Arabidopsis regulates leaf shape by polar cell
elongation independent of ROTUNDAFOLIA3 (ROT3). To expand our knowledge on the
function of this gens in plant systems, Arabidopsis LNG1 (AtLNG1) was introduced
both sense and antisense orientation under the control of 35S CaMV promoter into
tobacco plants that lack AtLNG1 homolog. Resulting transgenic tobacco plants were
analyzed by their phenotype, anatomy and transcript levels. AtLNG1-overexpressing
tobacco lines showed increase in the leaf petiole and leaf blade compared with
wild type tobacco line. The overexpressors also showed elongated palisade cells
as well as epidermal cells in the leaf length direction, but no increase in cell
number. Ectopic expression of AtLNG1 in tobacco plants also increased the
expression of cell wall modification-related genes, such as NT_XYLOGLUCAN
ENDOTRANSGLUCOSYLASE/HYDROLASE9 (NT_XTH9), NT_XTH15 and NT_XTH33, indicating that
these genes appear to be target of AtLNG1. As results of molecular and cellular
examination, AtLNG1 seemed to have a conserved functional role in shaping leaf
morphology in both Arabidopsis and tobacco.
PMID- 29949076
TI - Dependence and independence of the root clock on the shoot clock in Arabidopsis.
AB - Temporal and spatial compartmentalization of biological processes is facilitated
by tissue-specific uncoupled circadian clocks in plants. However, interactions
among tissue-specific circadian clocks have not been well established. The
primary objective of this study was to describe both organ-specific circadian
behaviors and centralized actions of the root clock. We analyzed transcript
accumulation of circadianly-oscillating genes in roots and shoots. Expression of
many clock components was different in roots and shoots. In particular, evening
expressed clock components were highly expressed in roots and likely play
important roles in oscillation of the root clock. Consistent with this, the root
and shoot clocks responded differentially to circadian gene mutations. The root
clock was even dampened in gi-2 mutant. Circadian clocks basically oscillate in
an organ-specific manner in plants, but the root clock also requires shoot
derived signals for organism-level coordination of circadian activity.
PMID- 29949078
TI - Recoverable Earth: a twenty-first century environmental narrative.
AB - Rewilding may signify the emergence of a new environmental narrative. Discussion
of underlying policy narratives is important because they shape understandings of
the state of world and how society should act. I summarise the origins of
twentieth century environmental narratives and argue that their influence derives
from components telling of the dire state of nature, the catastrophic
consequences of this and the need for competent authorities to act to govern the
perpetrators of harm. Reflecting on my engagements with rewilding science and
practice, I posit that stories of rewilding are adopting a quite different
narrative structure: one that involves components telling of feelings of
despondency and processes of awakening, action, and reassessment leading to the
recovery of natural and social well-being. These components align with the
narrative structure of accounts of mental health. I label this emerging narrative
'Recoverable Earth' and suggest that it signifies action by grassroot
conservationists to reassert their ability to lead change locally and produce
better outcomes for nature and society.
PMID- 29949077
TI - The complete mitochondrial genome of Vanessa indica and phylogenetic analyses of
the family Nymphalidae.
AB - Vanessa indica is a small butterfly lacking historical molecular and biological
research. Vanessa indica belongs to the family Nymphalidae (Lepidoptera:
Papilionoidea), which is the largest group of butterflies and are nearly
ubiquitous. However, after more than a century of taxonomic and molecular
studies, there is no consensus for family classification, and the phylogenetic
relationships within Nymphalidae are controversial. The first objective was to
sequence and characterize the complete mitochondrial genome of V. indica. The
most important objective was to completely reconstruct the phylogenetic
relationships for family members within Nymphalidae. The mitochondrial genomic
DNA (mtDNA) of V. indica was extracted and amplified by polymerase chain
reaction. The complete mitochondrial sequence was annotated and characterized by
analyzing sequences with SeqMan program. The phylogenetic analyses were conducted
on thirteen protein coding genes (PCGs) in 95 mtDNA of Nymphalidae downloaded
from GenBank for reference using the maximum likelihood method and Bayesian
inference to ensure the validity of the results. The complete mitogenome was a
circular molecule with 15,191 bp consisting of 13 protein coding genes, two
ribosomal RNA genes (16S rRNA and 12S rRNA), 22 transfer RNA (tRNA) genes, and an
A + T-rich region (D-loop). The nucleotide composition of the genome was highly
biased for A + T content, which accounts for 80.0% of the nucleotides. All the
tRNAs have putative secondary structures that are characteristic of mitochondrial
tRNAs, except tRNASer(AGN). All the PCGs started with ATN codons, except
cytochrome c oxidase subunit 1 (COX1), which was found to start with an unusual
CGA codon. Four genes were observed to have unusual codons: COX1 terminated with
atypical TT and the other three genes terminated with a single T. The A + T rich
region of 327 bp consisted of repetitive sequences, including a ATAGA motif, a 19
bp poly-T stretch, and two microsatellite-like regions (TA)8. The phylogenetic
analyses consistently placed Biblidinae as a sister cluster to Heliconiinae and
Calinaginae as a sister clade to Satyrinae. Moreover, the phylogenetic tree
identified Libytheinae as a monophyletic group within Nymphalidae. The complete
mitogenome of V. indica was 15,191 bp with mitochondrial characterizations common
for lepidopteran species, which enriched the mitochondria data of Nymphalid
species. And the phylogenetic analysis revealed different classifications and
relationships than those previously described. Our results are significant
because they would be useful in further understanding of the evolutionary biology
of Nymphalidae.
PMID- 29949079
TI - Implementation strategies for systematic conservation planning.
AB - The field of systematic conservation planning has grown substantially, with
hundreds of publications in the peer-reviewed literature and numerous
applications to regional conservation planning globally. However, the extent to
which systematic conservation plans have influenced management is unclear. This
paper analyses factors that facilitate the transition from assessment to
implementation in conservation planning, in order to help integrate assessment
and implementation into a seamless process. We propose a framework for designing
implementation strategies, taking into account three critical planning aspects:
processes, inputs, and context. Our review identified sixteen processes, which we
broadly grouped into four themes and eight inputs. We illustrate how the
framework can be used to inform context-dependent implementation strategies,
using the process of 'engagement' as an example. The example application includes
both lessons learned from successfully implemented plans across the engagement
spectrum, and highlights key barriers that can hinder attempts to bridge the
assessment-implementation gap.
PMID- 29949080
TI - Aligning conservation efforts with resource use around protected areas.
AB - A large number of economically disadvantaged people live around protected areas.
Conservation efforts that focus on poverty alleviation, work on the premise that
an increase in household wealth decreases use of forest resources. We surveyed
1222 households across four tiger reserves to test the paradigm that an increase
in assets leads to reduced forest use and we also assess the effects of other
socio-economic factors. We find that increase in assets may reduce Non-timber
Forest Product (NTFP) collection, but may not necessarily reduce livestock
numbers or use of wood as a cooking fuel. Households that faced more economic
setbacks were more likely to state that they wanted more livestock in the future.
Education is positively associated with choosing Liquefied Petroleum Gas as a
cooking fuel in the future. We find site and resource-specific variation. Fifty
percent of all households (range across sites: 6-98) want to collect NTFP while
91% (range: 87-96) want to retain or own more livestock over the next 5-10 years.
Understanding current and future resource use will help plan context-specific
conservation efforts that are better aligned with reducing specific pressures
around protected areas.
PMID- 29949081
TI - Effects of bird community dynamics on the seasonal distribution of cultural
ecosystem services.
AB - Biodiversity-based cultural ecosystem services (CES), such as birdwatching, are
strongly influenced by biotic community dynamics. However, CES models are largely
static, relying on single estimates of species richness or land-use/land-cover
proxies, and may be inadequate for landscape management of CES supply. Using bird
survey data from the Appalachian Mountains (USA), we developed spatial-temporal
models of five CES indicators (total bird species richness, and richness of
migratory, infrequent, synanthrope, and resident species), reflecting variation
in birdwatcher preferences. We analyzed seasonal shifts in birdwatching supply
and how those shifts impacted public access to projected birdwatching hotspots.
Landscape patterns of CES supply differed substantially among indicators, leading
to opposing conclusions about locations of highest birdwatching supply. Total
species richness hotspots seldom overlapped with hotspots of migratory or
infrequent species. Public access to CES hotspots varied seasonally. Our study
suggests that simple, static biodiversity metrics may overlook spatial dynamics
important to CES users.
PMID- 29949082
TI - Effect of visual distraction on children's anxiety during dental treatment: a
crossover randomized clinical trial.
AB - AIM: This was to evaluate the effect of visual distraction on anxiety of children
during dental treatment. MATERIALS AND METHODS: This randomized, crossover
clinical trial study was conducted on 28 children (aged 4-5 years) randomly
divided into two groups of 14 each. Group 1, treatment procedure in the first
visit was completed while the patients were watching a cartoon as a visual
distraction tool, at the second visit, the procedure was carried out with
conventional tell-show-do. Group 2, had visual distraction in their second visit
and conventional tell-show-do during the first visit. Treatment procedures were
similar in both groups during two sessions. The anxiety level was determined
using Venham picture test and pulse rate (PR) at the beginning and the end of
each appointment. Patient behaviour was also scored using Frankl behaviour rating
scale (FBRS). RESULTS: Self-reported dental anxiety was reduced significantly by
visual distraction (p-value < 0.001) compared to conventional tell-show-do, but
it did not change FBRS scores significantly (p-value = 0.24). CONCLUSION: Use of
visual distraction improves self-reported anxiety and decreases PR of children
but does not change their behaviour.
PMID- 29949083
TI - Paediatric dental emergencies: a retrospective study and a proposal for
definition and guidelines including pain management.
AB - AIM: This was primarily to perform a retrospective analysis of 1000 emergency
dental visits in order to characterize the nature of the dental emergency and the
treatment provided and secondly to define a guideline for dental emergency
treatment in children including pain management. MATERIALS AND METHODS: A
retrospective review was conducted of 1000 patients (aged 0-16 years) who visited
the dental emergency service of the paediatric dental clinic at the Ghent
University Hospital, Belgium over a period of 3 years. Data regarding age,
gender, reason for visit, year of visit, consequent appointments and treatment
provided were collected. Statistical analysis was carried out using descriptive
statistics (frequency distribution) and Chi-square test, with significance level
set as P < 0.05. RESULTS: The number of patients visiting with a dental emergency
increased annually. Approximately half (50.2%) of all paediatric dental emergency
consultations were based on pain due to caries and its consequences. More than a
quartile (26.7%) of emergency patients suffered from dental trauma of either
primar or permanent teeth. The majority (96.7%) of the patients reported pain,
16.3% of the patients did not necessarily need immediate attention. CONCLUSION:
Dental emergencies in a university hospital based setting were predominantly
related to caries and trauma. A precise definition of dental emergencies is
recommended in order to prevent abuse of paediatric emergency services.
PMID- 29949084
TI - Same-Sex Married Tax Filers After Windsor and Obergefell.
AB - This article provides new estimates of the number and characteristics of same-sex
married couples after U.S. Supreme Court rulings in 2013 and 2015 established
rights to same-sex marriage. The U.S. Department of the Treasury and the Internal
Revenue Service subsequently ruled that same-sex spouses would be treated as
married for federal tax purposes. Because almost all married taxpayers file joint
tax returns, administrative tax records provide new information on the
demographic characteristics of married same-sex couples. This study provides
estimates of the population of same-sex tax filers drawn from returns filed in
2013, 2014, and 2015, using methods developed by the U.S. Census Bureau to
address measurement error in gender classification. We estimate that
approximately 0.48 % of all joint filers in 2015 were same-sex couples, or
approximately 250,450 couples.
PMID- 29949085
TI - Organized Violence and Institutional Child Delivery: Micro-Level Evidence From
Sub-Saharan Africa, 1989-2014.
AB - The conditions under which a mother gives birth greatly affect the health risk of
both the mother and the child. This article addresses how local exposure to
organized violence affects whether women give birth in a health facility. We
combine geocoded data on violent events from the Uppsala Conflict Data Program
with georeferenced survey data on the use of maternal health care services from
the Demographic and Health Surveys. Our sample covers 569,201 births by 390,574
mothers in 31 countries in sub-Saharan Africa. We use a mother fixed-effects
analysis to estimate the effect of recent organized violence events within a
radius of 50 km of the home of each mother on the likelihood that her child is
born in a health facility. The results indicate that geographical and temporal
proximity to organized violence significantly reduces the likelihood of
institutional births. Although the level of maternal health care overall is lower
in rural areas, the negative effect of violence appears to be stronger in urban
areas. The study further underscores the importance of household and individual
resilience, indicating that the effect of organized violence on institutional
child delivery is greater among poor and less-educated mothers.
PMID- 29949086
TI - Prolonged Blood-Brain Barrier Injury Occurs After Experimental Intracerebral
Hemorrhage and Is Not Acutely Associated with Additional Bleeding.
AB - Intracerebral hemorrhage (ICH) causes blood-brain barrier (BBB) damage along with
altered element levels in the brain. BBB permeability was quantified at 3, 7, and
14 days with Evans Blue dye after collagenase-induced ICH in rat. At peak
permeability (day 3), a gadolinium (Gd)-based contrast agent was injected to
further characterize BBB disruption, and X-ray fluorescence imaging (XFI) was
used to map Gd, Fe, Cl, and other elements. XFI revealed that Ca, Cl, Gd, and Fe
concentrations were significantly elevated, whereas K was significantly
decreased. Therefore, using Gd-XFI, we co-determined BBB dysfunction with
alterations in the metallome, including those that contribute to cell death and
functional outcome. Warfarin was administered 3 days post-ICH to investigate
whether additional or new bleeding occurs during peak BBB dysfunction, and
hematoma volume was assessed on day 4. Warfarin administration prolonged bleeding
time after a peripheral cut-induced bleed, but warfarin did not worsen hematoma
volume. Accordingly, extensive BBB leakage occurred after ICH, but did not appear
to affect total hematoma size.
PMID- 29949087
TI - Radiologic Cerebral Reperfusion at 24 h Predicts Good Clinical Outcome.
AB - Cerebral reperfusion and arterial recanalization are radiological features of the
effectiveness of thrombolysis in acute ischemic stroke (AIS) patients. Here, an
investigation of the prognostic role of early recanalization/reperfusion on
clinical outcome was performed. In AIS patients (n = 55), baseline computerized
tomography (CT) was performed <= 8 h from symptom onset, whereas CT determination
of reperfusion/recanalization was assessed at 24 h. Multiple linear and logistic
regression models were used to correlate reperfusion/recanalization with
radiological (i.e., hemorrhagic transformation, ischemic core, and penumbra
volumes) and clinical outcomes (assessed as National Institutes of Health Stroke
Scale [NIHSS] reduction >= 8 points or a NIHSS <= 1 at 24 h and as modified
Rankin Scale [mRS] < 2 at 90 days). At 24 h, patients achieving radiological
reperfusion were n = 24, while the non-reperfused were n = 31. Among non
reperfused, n = 15 patients were recanalized. Radiological reperfusion vs.
recanalization was also confirmed by early increased levels of circulating
inflammatory biomarkers (i.e., serum osteopontin). In multivariate analysis,
ischemic lesion volume reduction was associated with both recanalization (beta =
0.265; p = 0.014) and reperfusion (beta = 0.461; p < 0.001), but only reperfusion
was independently associated with final infarct volume (beta = - 0.333; p =
0.007). Only radiological reperfusion at 24 h predicted good clinical response at
day 1 (adjusted OR 16.054 [1.423-181.158]; p = 0.025) and 90-day good functional
outcome (adjusted OR 25.801 [1.483-448.840]; p = 0.026). At ROC curve analysis
the AUC of reperfusion was 0.777 (p < 0.001) for the good clinical response at 24
h and 0.792 (p < 0.001) for 90-day clinical outcome. Twenty-four-hour
radiological reperfusion assessed by CT is associated with good clinical response
on day 1 and good functional outcome on day 90 in patients with ischemic stroke.
PMID- 29949088
TI - A prediction rule for early recognition of patients with candidemia in Internal
Medicine: results from an Italian, multicentric, case-control study.
AB - PURPOSE: Increasing prevalence of candidemia in Internal Medicine wards (IMWs)
has been reported in recent years, but risk factors for candida bloodstream
infection in patients admitted to IMW may differ from those known in other
settings. The aim of this study was to identify risk factors and define a
prediction rule for the early recognition of the risk of candidemia in IMW
inpatients. METHODS: This was a multicentric, retrospective, observational case
control study on non-neutropenic patients with candidemia admitted to IMWs of
four large Italian Hospitals. Each eligible patient with candidemia (case) was
matched to a control with bacteremia. Stepwise logistic regression analyses were
performed. RESULTS: Overall, 300 patients (150 cases and 150 controls) were
enrolled. The following factors were associated with an increased risk of
candidemia and weighted to build a score: total parenteral nutrition (OR 2.45, p
= 0.008; 1 point); central venous catheter (OR 2.19, p = 0.031; 1 point);
peripherally inserted central catheter (OR 5.63, p < 0.0001; 3 points),
antibiotic treatment prior (OR 2.06; p = 0.059; 1 point) and during
hospitalization (OR2.38, p = 0.033; 1 point); neurological disability (OR 2.25, p
= 0.01; 1 point); and previous hospitalization within 3 months (OR 1.56, p =
0.163; 1 point). At ROC curve analysis, a final score >= 4 showed 84%
sensitivity, 76% specificity, and 80% accuracy in predicting the risk of
candidemia. CONCLUSIONS: The proposed scoring system showed to be a simple and
highly performing tool in distinguishing bloodstream infections due to Candida
and bacteria in patients admitted to IMW. The proposed rule might help to reduce
delay in empirical treatment and improve appropriateness in antifungal
prescription in septic patients.
PMID- 29949089
TI - Invasive Candida auris infections in Kuwait hospitals: epidemiology, antifungal
treatment and outcome.
AB - PURPOSE: Candida auris is a recently recognized yeast pathogen, which has
attracted worldwide attention due to its multidrug-resistant nature and
associated high mortality rates. Its persistence in hospital environment and
propensity of nosocomial transmission underscores the need of continuous
monitoring to prevent outbreaks. Since the first case of C. auris candidemia in
May, 2014, we have identified 17 additional invasive cases, which are described
here. METHODS: Identity of 17 isolates originating from proven or possible cases
of invasive C. auris infection and identified as Candida haemulonii by Vitek 2
yeast identification system was confirmed by PCR-sequencing of rDNA. Information
about risk factors, treatment and outcomes were retrospectively retrieved from
case files. Antifungal susceptibility testing was performed by Etest. RESULTS:
Thirteen cases of candidemia and 4 cases of other invasive infections were
detected in 6 hospitals across Kuwait. Major risk factors included adult patients
with cancer, diabetes, gastrointestinal/liver diseases and extended (> 25 days)
hospital stay. All isolates were resistant to fluconazole. Additionally, 5 and 4
isolates were also resistant to voriconazole and amphotericin B, respectively.
Despite antifungal treatment, 9 of 15 patients died. Most patients (n = 12) were
hospitalized in 2 hospitals that are in close proximity, whereas 5 other patients
were from 3 hospitals that are situated > 10 km apart. CONCLUSIONS: Occurrence of
successive cases of invasive C. auris infections with resulting mortality in nine
patients suggests persistence of this multidrug-resistant yeast in major
hospitals in Kuwait. Early detection by continuous surveillance and enforcement
of infection control measures are recommended.
PMID- 29949090
TI - Onset of symptoms, diagnostic confirmation, and occurrence of multiple infective
foci in patients with Staphylococcus aureus bloodstream infection: a look into
the order of events and potential clinical implications.
AB - PURPOSE: Data on the systemic dissemination in Staphylococcus aureus bloodstream
infection (SAB) remain sparse. We investigated the timing and the sequence of
clinical symptoms, diagnostic confirmation, and occurrence of multiple infective
foci in relation to three major infective foci. METHODS: From 2006 to 2011, all
adult patients with first-time SAB in Cologne and Freiburg, Germany were followed
prospectively. The study was restricted to patients with short-term central
venous catheter (CVC)-related SAB, vertebral osteomyelitis (VO), and infective
endocarditis (IE). The collection date of the first positive blood culture was
used as reference point for determining time to onset of clinical symptoms,
microbiological findings, imaging results compatible with focal infection, and
occurrence of additional infective foci. RESULTS: We included 266 patients with
first-time SAB. Among patients with CVC-related SAB, clinical onset, collection
of the first positive blood culture, and microbiological confirmation almost
coincided. In contrast, among patients with VO or IE, the onset of clinical
symptoms most often preceded the collection of the first positive blood culture,
and imaging and microbiological confirmation were most frequently obtained
subsequent to the SAB diagnosis. CVC-related SAB was infrequently associated with
further foci (n = 15/15.5%). Conversely, more than one infective focus was
observed in 44 (56.4%) patient with VO and 68 (64.8%) patients with IE.
CONCLUSIONS: The sequence of clinical symptoms, diagnostic confirmation, and
occurrence of multiple infective foci varied considerably with different
infective foci in SAB. Based on these results, we propose a pragmatic and
evidence-based terminology for the clinical course of SAB and suggest the terms
"portal of entry", "infective focus", "multiple infective foci", and "dominant
infective focus".
PMID- 29949091
TI - In asking the right questions, be cautious of confounding by indication.
PMID- 29949092
TI - [Assessment of the therapeutic communication in order to improve the welcoming of
patients in the operating room: impact study].
AB - PURPOSE: We wanted to assess the awareness of the nursing staff to therapeutic
communications on improving the welcoming experience of patients in the operating
room for outpatient surgery. METHODS: This was a single centre prospective impact
study performed in an outpatient surgery clinic. In a first phase, a
questionnaire was administered by the anesthetist nurse upon arrival of the
patient to assess the patient's comfort (NRSc) and satisfaction on a simple
numeric scale, and calculate a negative communication score ('NC'). In the second
phase, the awareness of the nursing staff on therapeutic communication was
emphasized on listening, empathy and the use of positive wording, using
educational videos. In the third phase, after the staff awareness-raising period,
the questionnaire was repeated. Quantitative variables (primary outcome criterion
made of the number of patients with a NC score >= 5, NRSc, satisfaction), and
qualitative variables before and after the awareness raising phase to therapeutic
communications were compared. RESULTS: A total of 234 patients were included (109
before and 125 after). Following the staff awareness session to therapeutic
communication, the NC score >= 5 decreased significantly from 20% to 6% as well
as the median NRSc [P25-P75] before (8 [8-9] vs 8 [7-8]) and after (8 [8-9] vs 8
[7-8]) anesthesia. The proportion of less anxious patients before the initiation
of anesthesia was significantly higher after the therapeutic communication (32%
vs 17%). Satisfaction significantly increased after the awareness phase (8 [7-10]
vs (9 [8-10]). CONCLUSION: This preliminary study shows a mild improvement of the
patients' comfort and satisfaction after therapeutic communication. A controlled
randomized trial is needed to confirm those results.
PMID- 29949093
TI - Intensity of care and withdrawal of life-sustaining therapies in severe traumatic
brain injury patients: a post-hoc analysis of a multicentre retrospective cohort
study.
AB - PURPOSE: The intensity of care provided to critically ill patients has been shown
to be associated with mortality. In patients with traumatic brain injury (TBI),
specialized neurocritical care is often required, but whether it affects
clinically significant outcomes is unknown. We aimed to determine the association
of the intensity of care on mortality and the incidence of withdrawal of life
sustaining therapies in critically ill patients with severe TBI. METHODS: We
conducted a post hoc analysis of a multicentre retrospective cohort study of
critically ill adult patients with severe TBI. We defined the intensity of care
as a daily cumulative sum of interventions during the intensive care unit stay.
Our outcome measures were all-cause hospital mortality and the incidence of
withdrawal of life-sustaining therapies. RESULTS: Seven hundred sixteen severe
TBI patients were included in our study. Most were male (77%) with a mean
(standard deviation) age of 42 (20.5) yr and a median [interquartile range]
Glasgow Coma Scale score of 3 [3-6]. Our results showed an association between
the intensity of care and mortality (hazard ratio [HR], 0.69; 95% confidence
interval [CI], 0.63 to 0.74) and the incidence of withdrawal of life-sustaining
therapy (HR, 0.73; 95% CI, 0.67 to 0.79). CONCLUSION: In general, more intense
care was associated with fewer deaths and a lower incidence of withdrawal of life
sustaining therapies in critically ill patients with severe TBI.
PMID- 29949094
TI - Longitudinal Preterm Cerebellar Volume: Perinatal and Neurodevelopmental Outcome
Associations.
AB - Impaired cerebellar development is an important determinant of adverse motor and
cognitive outcomes in very preterm (VPT) infants. However, longitudinal MRI
studies investigating cerebellar maturation from birth through childhood and
associated neurodevelopmental outcomes are lacking. We aimed to compare
cerebellar volume and growth from term-equivalent age (TEA) to 7 years between
VPT (< 30 weeks' gestation or < 1250 g) and full-term children; and to assess the
association between these measures, perinatal factors, and 7-year outcomes in VPT
children, and whether these relationships varied by sex. In a prospective cohort
study of 224 VPT and 46 full-term infants, cerebellar volumes were measured on
MRI at TEA and 7 years. Useable data at either time-point were collected for 207
VPT and 43 full-term children. Cerebellar growth from TEA to 7 years was compared
between VPT and full-term children. Associations with perinatal factors and 7
year outcomes were investigated in VPT children. VPT children had smaller TEA and
7-year volumes and reduced growth. Perinatal factors were associated with smaller
cerebellar volume and growth between TEA and 7 years, namely, postnatal
corticosteroids for TEA volume, and female sex, earlier birth gestation, white
and deep nuclear gray matter injury for 7-year volume and growth. Smaller TEA and
7-year volumes, and reduced growth were associated with poorer 7-year IQ,
language, and motor function, with differential relationships observed for male
and female children. Our findings indicate that cerebellar growth from TEA to 7
years is impaired in VPT children and relates to early perinatal factors and 7
year outcomes.
PMID- 29949096
TI - Visuospatial Organization and Recall in Cerebellar Ataxia.
AB - Poor visuospatial skills can disrupt activities of daily living. The cerebellum
has been implicated in visuospatial processing, and patients with cerebellar
injury often exhibit poor visuospatial skills, as measured by impaired memory for
the figure within the Rey-Osterrieth complex figure task (ROCF). Visuospatial
skills are an inherent aspect of the ROCF; however, figure organization (i.e.,
the order in which the figure is reconstructed by the participant) can influence
recall ability. The objective of this study was to examine and compare
visuospatial and organization skills in people with cerebellar ataxia. We
administered the ROCF to patients diagnosed with cerebellar ataxia and healthy
controls. The cerebellar ataxia group included patients that carried a diagnosis
of spinocerebellar ataxia (any subtype), autosomal dominant cerebellar ataxia, or
cerebellar ataxia with unknown etiology. Primary outcome measures were
organization and recall performance on the ROCF, with supplemental information
derived from cognitive tests of visuospatial perception, working memory,
processing speed, and motor function. Cerebellar ataxia patients revealed
impaired figure organization relative to that of controls. Figure copy was
impaired in the patients, but their subsequent recall performance was normal,
suggesting compensation from initial organization and copying strategies. In
controls, figure organization predicted recall performance, but this relationship
was not observed in the patients. Instead, processing speed predicted patients'
recall accuracy. Supplemental tasks indicated that visual perception was intact
in the cerebellar ataxia group and that performance deficits were more closely
tied to organization strategies than with visuospatial skills.
PMID- 29949097
TI - An Opponent Process Cerebellar Asymmetry for Regulating Word Association Priming.
AB - A consensus has emerged that the cerebellum makes important contributions to a
spectrum of linguistic processes, but that the psychobiology of these
contributions remains enigmatic (Marien et al., Cerebellum 13(3):386-410, 2014).
One aspect of this enigma arises from the fact that, although the language
dominant left cerebral hemisphere is connected to the right cerebellum,
distinctive contributions of the left cerebellar hemisphere have been documented
(Murdoch and Whelan, Folia Phoniatr Logop 59:184-9, 2007), but remain poorly
understood. Here, we report that neurodisruption of the left and right cerebellar
hemispheres have opposite effects on associative word priming in a lexical
decision task. Reaction time was measured for decisions on whether a target
letter string constituted a word (e.g. bread) or, with equal probability, a
pronounceable non-word (e.g. dreab). A prime word was presented for 150 ms before
the target and could either, and with equal probability, be related (e.g. BUTTER)
or unrelated (TRACTOR). Associative word priming was computed as the reduction in
lexical decision RT on trials with related primes. Left cerebellar hemisphere
continuous theta-burst transcranial magnetic stimulation (TMS) decreased, and
right hemisphere stimulation increased, priming. The results suggest that the
cerebellum contributes to predictive sequential processing, in this case
language, through an opponent process mechanism coordinated by both cerebellar
hemispheres.
PMID- 29949095
TI - C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an
adult-onset progressive SCA13 with spasticity.
AB - Mutations in the potassium channel gene KCNC3 (Kv3.3) cause the autosomal
dominant neurological disease, spinocerebellar ataxia 13 (SCA13). In this study,
we expand the genotype-phenotype repertoire of SCA13 by describing the novel
KCNC3 deletion p.Pro583_Pro585del highlighting the allelic heterogeneity observed
in SCA13 patients. We characterize adult-onset, progressive clinical symptoms of
two afflicted kindred and introduce the symptom of profound spasticity not
previously associated with the SCA13 phenotype. We also present molecular and
electrophysiological characterizations of the mutant protein in mammalian cell
culture. Mechanistically, the p.Pro583_Pro585del protein showed normal membrane
trafficking with an altered electrophysiological profile, including slower
inactivation and decreased sensitivity to the inactivation-accelerating effects
of the actin depolymerizer latrunculin B. Taken together, our results highlight
the clinical importance of the intracellular C-terminal portion of Kv3.3 and its
association with ion channel function.
PMID- 29949098
TI - Risk Differences in Disease-Specific Infant Mortality Between Black and White US
Children, 1968-2015: an Epidemiologic Investigation.
AB - PURPOSE: Black/African American (AA) infants have been persistently observed with
survival disadvantage compared to White infants in the USA, implying excess
mortality. While reliable epidemiologic data continue to illustrate these
disparities, data are yet to provide a substantial explanation to the observed
rates and risk differences over the past six decades. We aimed in this study to
examine the infant mortality risk differences by temporal trends and to provide
an ecologic and non-concurrent explanation for the persisted variability.
METHODS: A retrospective design with aggregate data from the Center for Disease
Control and Prevention (CDC) was used to access the risk difference in cause
specific mortality, while stratification analysis was utilized for the risk ratio
estimation. We also estimated the percent change for mortality trends. RESULTS:
The cumulative infant mortality (IM) incidence was two times as likely for
Black/AA relative to White, risk ratio (RR), 2.05. There were temporal trends in
IM between 1968 and 2015 with excess IM among Black/AA children. Specifically,
between 1968 and 2015, the percent change (% change) for digestive system
disorders (58.43%); genito-urinary tract system disorders (58.20%); muscle,
skeleton, and connective tissue disorders (66.60%); congenital anomalies
(23.79%); and certain perinatal causes (38.65%) indicated upward trends in infant
mortality Black/AA and White risk ratio. Except for neoplasm, and the initial
study period (1968-1978) for congenital anomalies, Black/AA infants indicated
survival disadvantage, implying excess mortality ratio relative to their White
counterparts. CONCLUSION: Disease-specific infant mortality is higher among
black/AA except for neoplasm, and increasing percent changes are observed in
digestive; genito-urinary; and muscle, skeleton, and connective tissue disorders.
These findings are suggestive of the pressing needs to examine the cause of these
disparities namely social determinants of health and social inequity for specific
risk-adapted intervention in achieving health equity in US infant mortality.
PMID- 29949099
TI - #MedEd: exploring the relationship between altmetrics and traditional measures of
dissemination in health professions education.
AB - INTRODUCTION: Researchers, funders, and institutions are interested in
understanding and quantifying research dissemination and impact, particularly
related to communicating with the public. Traditionally, citations have been a
primary impact measure; however, citations can be slow to accrue and focus on
academic use. Recently altmetrics, which track alternate dissemination forms (e.
g., social media), have been suggested as a complement to citation-based metrics.
This study examines the relationship between altmetrics and traditional measures:
journal article citations and access counts. METHODS: The researchers queried Web
of Science and Altmetric Explorer for articles published in HPE journals between
2013-2015. They identified 2,486 articles with altmetrics. Data were analyzed
using negative binomial and linear regression models. RESULTS: Blogging was
associated with the greatest increase in citations (13% increase), whereas Tweets
(1.2%) and Mendeley (1%) were associated with smaller increases. Journal impact
factor (JIF) was associated with a 21% increase in citations. Publicly accessible
articles were associated with a 19% decrease, but the interactive effect between
accessible articles and JIF was associated with a 12% increase. When examining
access counts, publicly accessible articles had an increase of 170 access counts
whereas blogging was associated with a decrease of 87 accesses. DISCUSSION: This
study suggests that several altmetrics outlets are positively associated with
citations, and that public accessibility, holding all other independent variables
constant, is positively related to article access. Given the scientific
community's evolving focus on dissemination these findings have implications for
stakeholders, providing insight into the factors that may improve citations and
access of articles.
PMID- 29949100
TI - What Future Healthcare Professionals Need to Know About Pharmacovigilance:
Introduction of the WHO PV Core Curriculum for University Teaching with Focus on
Clinical Aspects.
AB - Adverse drug reactions (ADRs) can cause serious health problems, as shown in
studies about drug-related hospitalizations. To build knowledge of and raise
awareness about ADRs among healthcare professionals, more education in the field
of ADRs and pharmacovigilance (PV) is needed. No standard exists for teaching PV
at universities for medical, pharmacy, dentistry and nursing students, so a core
curriculum needs to be developed to teach important aspects of PV to students. In
September 2016, a stakeholders' meeting was initiated on behalf of the World
Health Organization (WHO) and organized by the Netherlands Pharmacovigilance
Centre Lareb. This meeting addressed and agreed on the PV competencies students
need to develop and what key aspects of the subject should be taught. Five key
aspects were identified: understanding the importance of PV in the context of
pharmacotherapy, and preventing, recognizing, managing and reporting ADRs. Since
time and resources for PV education are limited, elements of the WHO PV core
curriculum for university teaching were designed to be integrated into existing
courses but can be used as a stand-alone programme. The basis of and outline for
the WHO PV core curriculum for university teaching are addressed in this paper.
It is expected that PV competencies for students are vital for their contribution
to safe use of medicines in the future. In addition, this article aims to
stimulate discussion on this subject and promote collaboration between
universities, national PV centres and other stakeholders to integrate key aspects
of PV in their educational programmes.
PMID- 29949101
TI - Atypical Post-Injection Reactions with Delayed Onset Following Glatiramer Acetate
40 mg: Need for Titration?
AB - BACKGROUND: Glatiramer acetate (GA) 20 mg/day (GA20) is associated with immediate
post-injection reactions (PIRs). For convenience of use, approved GA 40 mg three
times weekly (GA40) delivers a similar weekly dose. The dose and concentration of
a single GA40 injection are, however, twice as high as for GA20, and post
injection adverse events may differ. Cases of atypical PIRs to GA40 prompted us
to systematically monitor such events. OBJECTIVE: The aim was to characterize
atypical PIRs in multiple sclerosis (MS) patients treated with GA40. METHODS:
Clinical practice data were prospectively collected in consecutive relapsing
remitting MS patients. Descriptive statistics for categorical and continuous
variables, Mann-Whitney and Chi-squared tests for baseline comparisons, and Cox
regression models for association of variables to first atypical PIRs were
applied. RESULTS: Forty-six out of 173 patients (26.6%) given GA40 experienced
any PIRs. Of those, 38 (22.0%) had atypical, 14 (8.1%) had combined typical and
atypical, and 26 (15.0%) had recurrent atypical PIRs, most frequently shivering
(13.3%) and nausea/vomiting (8.1%). Compared to typical PIRs, onset of atypical
PIRs was significantly delayed (median 30 vs 1 min, p < 0.0001), and their median
duration longer (median 120 vs 6 min, p = 0.00013). Previous exposure to GA20 was
associated with a lower risk of atypical PIRs [hazard ratio (HR) = 0.35, 95%
confidence interval (CI) 0.17-0.72, p = 0.0039]. Patients experiencing PIRs with
GA20 were at elevated risk for atypical PIRs with GA40 (HR = 5.75, 95% CI 1.66
19.94, p = 0.0059). CONCLUSIONS: Atypical PIRs with GA40, especially
gastrointestinal symptoms and/or fever/shivering, had a delayed onset and
occurred in a significant proportion of our patients. Their real prevalence
should be assessed in appropriately designed studies accounting for nocebo
responses. Initial dose titration might reduce PIR frequency.
PMID- 29949103
TI - Comment on Mayock SP, Saim S, Fleming AB. In Vitro Drug Release After Crushing:
Evaluation of Xtampza(r) ER and Other ER Opioid Formulations.
PMID- 29949104
TI - Response to Crudele et al. Commentary on Mayock et al. "In Vitro Drug Release
after Crushing: Evaluation of Xtampza(r) ER and Other ER Opioid Formulations".
PMID- 29949102
TI - Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of
Verinurad, a Selective Uric Acid Reabsorption Inhibitor.
AB - : BACKGROUND AND OBJECTIVE: Verinurad (RDEA3170) is a high-affinity, selective
URAT1 transporter inhibitor in development for treating gout and asymptomatic
hyperuricemia. This Phase I, single-dose study investigated the pharmacokinetics,
pharmacodynamics, and safety of verinurad in adults with renal impairment and
controls with normal renal function. METHODS: Males aged 18-85 years were
enrolled with serum urate (sUA) 4.5-10 mg/dl and creatinine clearance 60- < 90,
30- < 60, 15- < 30, or >= 90 ml/min (mild, moderate, severe renal impairment and
controls, respectively; n = 7/8). Verinurad 15 mg was administered orally under
fasted conditions. Serial plasma/serum and urine samplings were 30 min pre-dose
to 72 h post-dose. RESULTS: Compared to controls, verinurad maximum observed
plasma concentration increased by 53, 73, and 128% and area under the
concentration-time curve increased by 24, 148, and 130%, in subjects with mild,
moderate, and severe renal impairment, respectively; renal clearance decreased by
5, 42, and 79%. Exposures of major verinurad metabolites also increased with
increasing renal impairment. Verinurad decreased sUA in all groups, with greater
maximal changes in control and mild renal impairment than moderate and severe
impairment groups (- 38.3, - 36.9, - 20.5, - 12.6%, respectively). There were no
adverse event-related withdrawals or clinically meaningful changes in laboratory
values. CONCLUSION: Exposures of verinurad and metabolites increased with
decreasing renal function. Consistent with the renal-dependent mechanism of
action of verinurad, increasing severity of renal impairment was associated with
decreased sUA lowering. Verinurad safety assessments were similar regardless of
renal impairment. Continued investigation of verinurad is warranted in patients
with gout and renal impairment. CLINICALTRIALS. GOV IDENTIFIER: NCT02219516.
PMID- 29949105
TI - Diagnostic Performance of Multidetector Computed Tomography (MDCT) to
Differentiate Malignant from Benign Ampullary Lesions Causing Distal Common Bile
Duct Obstruction.
AB - Objective: To evaluate diagnostic performance of 64-slice multidetector computed
tomography (MDCT) for differentiating the benign from malignant ampullary lesion.
Material and Method: A retrospective study was performed in 55 patients with
obstructive jaundice from distal common bile duct (CBD) obstruction as a result
of ampullary lesion underwent 64-slice MDCT. The patients were enrolled between
February 2007 and August 2014. The patients' MDCT scans of abdomen were
retrospectively evaluated by two gastrointestinal radiologists without knowledge
of patient's history, clinical data, and final diagnosis. Readers recorded the
presence or absence of ampullary mass, size, shape, margin, enhancing pattern of
ampullary lesion, diameter of CBD, and additional finding. Results: CBD
dilatation in malignancy and benign groups were 1.9+/-0.7 cm and 1.5+/-0.5 cm,
respectively (p<0.05). Intrahepatic duct dilatation was more present in malignant
ampullary lesion. Target pattern of ampullary lesion were found in only benign
group (p<0.05) and pancreatic divisum were found in only malignant group
(p>0.05). As compared pathological results and CT findings of benign and
malignant lesions represent 95.4% sensitivity and 58.3% specificity. Conclusion:
MDCT is helpful to differentiate benign and malignant nature of ampullary lesion
that causes distal CBD obstruction. Benign and malignant ampullary lesion that
cause distal CBD obstruction could not be definite differentiated by size,
density, and enhancement pattern on CT image but degree of CBD, intrahepatic duct
dilatation, pancreatic divisum, and target pattern may be distinguished.
PMID- 29949106
TI - Malfunctioning of Chaperone-Mediated Autophagy in Parkinson's Disease: Feats,
Constraints, and Flaws of Modulators.
AB - Homeostatic regulation of class II programmed cell death/autophagy for the
degradation and elimination of substandard organelles and defective proteins is
decisive for the survival of dopaminergic neurons. Chaperone-mediated autophagy
(CMA), one of the most highly dedicated self-sacrificing events, is accountable
for the partial elimination of redundant soluble cytoplasmic proteins in
Parkinson's disease (PD). CMA is characterized by the selective delivery of
superfluous protein containing lysine-phenylalanine-glutamate-arginine-glutamine
(KFERQ)/KFERQ-like motif to the lysosome through molecular chaperones, such as
heat shock cognate-70 (Hsc-70). KFERQ/KFERQ-like motif present in the poor
quality cytoplasmic substrate protein and Hsc-70 complex is recognized by a
janitor protein, which is referred to as the lysosome-associated membrane protein
2A (LAMP-2A). This protein is known to facilitate an entry of substrate-chaperone
complex in the lumen for hydrolytic cleavage of substrate and elimination of end
products. Impaired CMA is repeatedly blamed for an accumulation of surplus
soluble proteins. However, it is still an enigma if CMA is a bonus or curse for
PD. Case-control studies and cellular and animal models have deciphered the
contribution of impaired CMA in PD. Current article updates the role of CMA in
toxicant models and recapitulates the evidences that have highlighted a link
between impaired CMA and PD. Although PD is an irreversible happening and CMA is
a dual edging phenomenon, it is anticipated that fine-tuning of the latter
encounters the former to a certain extent. Besides, the truth, embellishment, and
propaganda regarding the issue are also emphasized in the final segment of the
article.
PMID- 29949107
TI - Comparing the Effects of Ferulic Acid and Sugarcane Aqueous Extract in In Vitro
and In Vivo Neurotoxic Models.
AB - Molecules exhibiting antioxidant, neuroprotective, and regulatory properties
inherent to natural products consumed by humans are gaining attention in
biomedical research. Ferulic acid (FA) is a phenolic compound possessing
antioxidant and cytoprotective properties. It is found in several vegetables,
including sugarcane, where it serves as the main antioxidant component. Here, we
compared the antioxidant and cytoprotective effects of FA with those of the total
sugarcane aqueous extract (SCAE). Specifically, we assessed biochemical markers
of cell dysfunction in rat cortical brain slices and markers of physiological
stress in Caenorhabditis elegans upon exposure to toxins evoking different
mechanisms of neurotoxicity, including direct oxidative stress and/or
excitotoxicity. In rat cortical slices, FA (250 and 500 MUM), but not SCAE (~ 270
MUM of total polyphenols), prevented the loss of reductive capacity induced by
the excitotoxin quinolinic acid (QUIN, 100 MUM), the pro-oxidant agent ferrous
sulfate (FeSO4, 25 MUM), and the dopaminergic pro-oxidant 6-hydroxydopamine (6
OHDA, 100 MUM). In wild-type (N2) C. elegans, FA (38 mM) exerted protective
effects on decreased survival induced by FeSO4 (15 mM) and 6-OHDA (25 mM), and
the motor alterations induced by QUIN (100 mM), FeSO4, and 6-OHDA. In contrast,
SCAE (~ 13.5 mM of total polyphenols) evoked protective effects on the decreased
survival induced by the three toxic agents, the motor alterations induced by
FeSO4, and the reproductive deficit induced by FeSO4. In addition, FA was unable
to reverse the decreased survival induced by all these toxins in the skn-1-/-
strain (VC1772), which lacks the homolog of mammalian Nrf2, a master antioxidant
gene. Altogether, our results suggest that (1) both FA and SCAE afford protection
against toxic conditions, (2) not all the effects inherent to SCAE are due to FA,
and (3) FA requires the skn-1 pathway to exert its protective effects in C.
elegans.
PMID- 29949108
TI - Threshold of Energy Deficit and Lower-Body Performance Declines in Military
Personnel: A Meta-Regression.
AB - BACKGROUND: Negative energy balance (EB) is common during military operations,
diminishing body mass and physical performance. However, the magnitude of
negative EB where performance would still be maintained is not well defined.
OBJECTIVE: Our objective was to explore relationships between EB and physical
performance during military operations and define an acceptable negative EB
threshold where performance may be maintained. METHODS: A systematic search was
performed for studies that measured EB and physical performance during military
training. A total of 632 articles and technical reports were screened. Lower-body
power and strength were the most common performance tests across investigations
and were used as physical performance outcomes. Data were extracted from nine
eligible studies containing 15 independent subgroups. Meta-regression assessed
changes in performance in relation to study duration (days), average daily EB,
and total EB (daily EB * duration). RESULTS: Changes in physical performance were
not associated with average daily EB or training duration. Total EB was
associated with changes in lower-body power (r2 = 0.764, P < 0.001) and strength
(r2 = 0.836, P < 0.001) independently and combined (r2 = 0.454, P = 0.002).
Predictive equations generated from the meta-regression indicated that, for a
zero to small (2%) decline in performance, total EB should be limited to - 5686
to - 19,109 kcal, for an entire operation, whereas total EB of - 39,243 to -
59,377 kcal will result in moderate (7%) to large (10%) declines in performance.
CONCLUSION: These data demonstrated that greater total negative EB is associated
with declines in lower-body performance during military operations.
PMID- 29949109
TI - Lower Limb Biomechanics During Single-Leg Landings Following Anterior Cruciate
Ligament Reconstruction: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) may not restore
lower limb biomechanics during single-limb landings. OBJECTIVES: Our objective
was to identify and evaluate differences in lower limb biomechanics during high
demand single-limb landings between the ACLR limb and the contralateral limb and
healthy control participants. METHODS: A systematic review of the literature was
conducted using six electronic databases searched until April 2017 for published
peer-reviewed studies that investigated lower limb biomechanics on the ACLR limb
compared with either the contralateral limb or those of control participants.
Meta-analysis with standardized mean differences (SMD) were performed for peak
angles and moments (hip, knee and ankle joints) in the sagittal plane during
single-limb landing tasks. RESULTS: A total of 35 studies met inclusion criteria.
Four different single-leg landing tasks were identified: forward hop (n = 24
studies), landing from a height (n = 9 studies), vertical hop (n = 4 studies),
and diagonal leap (n = 1 study). A reduced peak knee flexion angle was found in
the ACLR limb compared with the contralateral limb during a forward hop landing
task (SMD - 0.39; 95% confidence interval [CI] - 0.59 to - 0.18) and compared
with a control group (SMD between - 1.01 and - 0.45) for all three reported
single-leg landing tasks: forward hop, landing from a height, and diagonal leap.
Similarly, a reduced peak knee internal extensor moment was found in the ACLR
limb compared with the contralateral limb for all three reported landing tasks:
forward hop, landing from a height, vertical hop (SMD between - 1.43 and - 0.53),
and in two of three landing tasks when compared with a control group (SMD between
- 1.2 and - 0.52). No significant differences in peak flexion (hip and ankle)
angle or peak (hip and ankle) internal extensor moment were found in the ACLR
limb compared with both the contralateral limb and a control group. CONCLUSIONS:
Participants performed single-limb landings on the ACLR limb with reductions in
peak sagittal knee kinematics as well as peak joint moments compared with both
the contralateral limb and a control group. Stiffer single-leg landings
potentially expose the knee joint to higher forces, which may increase risk of
injury. Clinical testing after ACLR surgery should explore movement quality as
well as performance of functional tasks. LEVEL OF EVIDENCE: Case-control, IV.
PMID- 29949110
TI - Effects of High-Intensity Interval Training Versus Moderate-Intensity Continuous
Training On Blood Pressure in Adults with Pre- to Established Hypertension: A
Systematic Review and Meta-Analysis of Randomized Trials.
AB - BACKGROUND: Aerobic exercise reduces blood pressure (BP), but it is unknown
whether a high-intensity training approach can elicit a greater BP reduction in
populations with elevated BP. This systematic review compared the efficacy of
high-intensity interval training (HIIT) versus moderate-intensity continuous
training (MICT) for reducing BP in adults with pre- to established hypertension.
METHODS: Five electronic databases (MEDLINE, EMBASE, CENTRAL, PEDro, and
SPORTDiscus) were searched for randomized trials comparing the chronic effects of
HIIT versus MICT on BP in individuals with resting systolic BP >= 130 mmHg and/or
diastolic BP >= 85 mmHg and/or under antihypertensive medication. Random-effects
modelling was used to compare changes from pre- to post-intervention in resting
and ambulatory BP between HIIT and MICT. Changes from pre- to post-intervention
in maximal oxygen uptake ([Formula: see text]O2max) between HIIT and MICT were
also meta-analyzed. Data were reported as weighted mean difference (MD) and 95%
confidence interval (CI). RESULTS: Ambulatory BP was excluded from the meta
analysis due to the limited number of studies (two studies). Comparing changes
from pre- to post-intervention, no differences in resting systolic BP (MD - 0.22
mmHg [CI 95%, - 5.36 to 4.92], p = 0.93, I2 = 53%) and diastolic BP (MD - 0.38
mmHg [CI 95%, - 3.31 to 2.54], p = 0.74, I2 = 0%) were found between HIIT and
MICT (seven studies; 164 participants). HIIT improved [Formula: see text]O2max to
a greater magnitude than MICT (MD 2.13 ml/kg/min [CI 95%, 1.00 to 3.27], p <
0.01, I2 = 41%) with similar completion rates of the intervention and attendance
at the exercise training sessions (nine studies; 245 participants). Limited data
were available to compare the incidence of adverse events between HIIT and MICT.
CONCLUSION: HIIT and MICT provided comparable reductions in resting BP in adults
with pre- to established hypertension. HIIT was associated with greater
improvements in [Formula: see text]O2max when compared to MICT. Future randomized
trials should investigate the efficacy of HIIT versus MICT for reducing
ambulatory BP in adults with pre- to established hypertension. REGISTRATION:
PROSPERO registration (2016: CRD42016041885).
PMID- 29949111
TI - Functional connectivity of reflective and brooding rumination in depressed and
healthy women.
AB - Ruminative thinking is related to an increased risk for major depressive disorder
(MDD) and perpetuates negative mood states. Rumination, uncontrollable negative
thoughts about the self, may comprise both reflective and brooding components.
However, only brooding rumination is consistently associated with increased
negativity bias and negative coping styles, while reflective rumination has a
less clear relationship with negative outcomes in healthy and depressed
participants. The current study examined seed-to-voxel (S2.V) resting-state
functional connectivity (FC) in a sample of healthy (HC) and depressed (MDD)
adult women (HC: n=50, MDD: n=33). The S2V FC of six key brain regions, including
the left and right amygdala, anterior and posterior cingulate cortex (ACC, PCC),
and medial and dorsolateral prefrontal cortices (mPFC, dlPFC), was correlated
with self-reported reflective and brooding rumination. Results indicate that HC
and MDD participants had increased brooding rumination associated with decreased
FC between the left amygdala and the right temporal pole. Moreover, reflective
rumination was associated with distinct FC of the mPFC, PCC, and ACC with
parietal, occipital, and cingulate regions. Depressed participants, compared with
HC, exhibited decreased FC between the PCC and a region in the right middle
frontal gyrus. The results of the current study add to the understanding of the
neural underpinnings of different forms of self-related cognition-brooding and
reflective rumination-in healthy and depressed women.
PMID- 29949112
TI - Age differences in the neural response to emotional distraction during working
memory encoding.
AB - Age-related declines in attention and working memory (WM) are well documented and
may be worsened by the occurrence of distracting information. Emotionally
valenced stimuli may have particularly strong distracting effects on cognition.
We investigated age-related differences in emotional distraction using task-fMRI.
WM performance in older adults was lower for emotional compared with neutral
distractors, suggesting a disproportional impairment elicited by emotional task
irrelevant information. Critically, older adults were particularly distracted by
task-irrelevant positive information, whereas the opposite pattern was found for
younger adults. Age groups differed markedly in the brain response to emotional
distractors; younger adults activated posterior cortical regions and the
striatum, and older adults activated frontal regions. Also, an age by valence
interaction was found for IFG and ACC, suggesting differential modulation of
attention to task-relevant emotional information. These results provide new
insights into age-related changes in emotional processing and the ability to
resolve interference from emotional distraction.
PMID- 29949113
TI - The effects of expected reward on creative problem solving.
AB - Creative problem solving involves search processes, and it is known to be hard to
motivate. Reward cues have been found to enhance performance across a range of
tasks, even when cues are presented subliminally, without being consciously
detected. It is uncertain whether motivational processes, such as reward, can
influence problem solving. We tested the effect of supraliminal and subliminal
reward on participant performance on problem solving that can be solved by
deliberate analysis or by insight. Forty-one participants attempted to solve 100
compound remote associate problems. At the beginning of each problem, a potential
reward cue (1 or 25 cents) was displayed, either subliminally (17 ms) or
supraliminally (100 ms). Participants earned the displayed reward if they solved
the problem correctly. Results showed that the higher subliminal reward increased
the percentage of problems solved correctly overall. Second, we explored if
subliminal rewards preferentially influenced solutions that were achieved via a
sudden insight (mostly processed below awareness) or via a deliberate analysis.
Participants solved more problems via insight following high subliminal reward
when compared with low subliminal reward, and compared with high supraliminal
reward, with no corresponding effect on analytic solving. Striatal dopamine (DA)
is thought to influence motivation, reinforce behavior, and facilitate cognition.
We speculate that subliminal rewards activate the striatal DA system, enhancing
the kinds of automatic integrative processes that lead to more creative
strategies for problem solving, without increasing the selectivity of attention,
which could impede insight.
PMID- 29949114
TI - The effects of attention and task-relevance on the processing of syntactic
violations during listening to two concurrent speech streams.
AB - The notion of automatic syntactic analysis received support from some event
related potential (ERP) studies. However, none of these studies tested syntax
processing in the presence of a concurrent speech stream. Here we present two
concurrent continuous speech streams, manipulating two variables potentially
affecting speech processing in a fully crossed design: attention (focused vs.
divided) and task (lexical - detecting numerals vs. syntactical - detecting
syntactic violations). ERPs elicited by syntactic violations and numerals as
targets were compared with those for distractors (task-relevant events in the
unattended speech stream) and attended and unattended task-irrelevant events. As
was expected, only target numerals elicited the N2b and P3 components. The
amplitudes of these components did not significantly differ between focused and
divided attention. Both task-relevant and task-irrelevant syntactic violations
elicited the N400 ERP component within the attended but not in the unattended
speech stream. P600 was only elicited by target syntactic violations. These
results provide no support for the notion of automatic syntactic analysis.
Rather, it appears that task-relevance is a prerequisite of P600 elicitation,
implying that in-depth syntactic analysis occurs only for attended speech under
everyday listening situations.
PMID- 29949115
TI - Development of antibody mediated rejection shortly after acute cellular rejection
in a pediatric kidney transplantation recipient.
AB - Acute rejection is a major cause of graft loss in patients with kidney
transplantations. However, the appropriate timing for performing a biopsy is
often difficult to gauge in a clinical settings. We encountered an 8-year-old boy
in whom antibody mediated rejection (AMR) associated with de novo donor-specific
antibody (DSA) developed shortly after an episode of type IA acute cellular
rejection (ACR). He had received a preemptive ABO-compatible kidney
transplantation due to bilateral renal hypoplasia. Type IA ACR developed 2 months
after transplantation and was successfully treated with methylprednisolone pulse
therapy (MPT) and gusperimus hydrochloride. However, 4 months after
transplantation, his serum creatinine level increased again. We decided to
perform an additional biopsy despite having done the previous biopsy only a short
time ago. Marked infiltration of inflammation cells in the peritubular
capillaries (PTCs) with positive C4d staining was observed. AMR associated with
de novo DSA with type IB ACR was newly diagnosed because DSA was not detected and
the crossmatch test was negative before transplantation. He immediately received
two courses of plasma exchange (PE), three courses of MPT, and rituximab. He
confessed to non-adherence and underwent a patient education program with his
family again. To date, no cases of AMR associated with de novo DSA shortly after
ACR have been reported. Our experience lends support to the 'episode biopsy'
method in which a biopsy is performed for each episode of serum creatinine
increase as recommended by The Kidney Disease: Improving Global Outcomes (KDIGO)
Transplant Working Group.
PMID- 29949116
TI - A case of cerebral infarction during a hemodialysis procedure successfully
treated with recombinant tissue plasminogen activator.
AB - Thrombolytic therapy is an effective treatment for acute ischemic stroke and
provides benefits and improvements that lead to better neurological outcomes.
However, thrombolytic therapy with recombinant tissue plasminogen activator (r
tPA) in hemodialysis (HD) patients is limited because HD patients have a higher
risk of bleeding. We report a case of a 75-year-old HD patient who presented with
sudden aphasia during HD treatment. She was brought to the hospital for treatment
for infarction. Following thrombolytic therapy, we achieved re-opening without
complications. To our knowledge, no report has been published describing the
patients who had a stroke during a maintenance HD session and were treated with r
tPA successfully. Although the number of HD patients treated with r-tPA is small
and requires further investigation, thrombolytic therapy can be an alternative
option. After weighing the risks and benefits and assessing each patient
carefully, the use of r-tPA should be considered, even in HD patients.
PMID- 29949117
TI - Testing the role of response repetition in spatial priming in visual search.
AB - In common "attention" tasks, which require stimulus-identity processing prior to
the formation of a speeded key-press response, spatial priming effects depend on
response repetition. Typically, the repetition of a stimulus location is
advantageous when the prior response repeats, but disadvantageous or
inconsequential when the prior response changes. This link between responding and
space makes it difficult to draw inferences about attentional bias from two
choice key-press tasks. Instead, the findings are accounted for by episodic
retrieval theories, which argue that the response associated with a prior
stimulus location is retrieved when a later stimulus occupies its space. This
retrieval operation is advantageous if the prior response is needed but not
otherwise, which explains typical patterns. This perspective motivated us to
evaluate whether spatial priming effects in the visual-search literature depend
critically on response repetition. To assess this, we reevaluated a series of
experiments recently published by Tower-Richardi, Leber, and Golomb (Attention,
Perception, & Psychophysics, 78(1), 114-132, 2016). Their goal was to determine
the reference frame of spatial priming across visual search displays.
Reassessment reveals that spatial priming was strongly dependent on response
repetition when spatiotopic, retinotopic, and object-centered reference frames
were perfectly confounded. However, when eye movements were made to dissociate
the spatiotopic and object-centered reference frame from the retinotopic
reference frame, spatial priming was positive and unaffected by response
repetition. The findings demonstrate that at least two distinct processes factor
into spatial priming across visual searches, which occur at different levels of
representation.
PMID- 29949118
TI - Salience drives overt selection of two equally relevant visual targets.
AB - In the present study, we investigated whether salience determines the sequence of
selection when participants search for two equally relevant visual targets. To do
this, attentional selection was tracked overtly as observers inspected two items
of differing physical salience: one a highly salient color singleton, and the
other a less salient shape singleton. Participants were instructed to make
natural eye movements in order to determine whether two line segments contained
within the two singletons were oriented in the same or in different directions.
Because both singleton items were task-relevant, participants had no reason to
inspect one item before the other. As expected, observers fixated both targets on
the majority of trials. Critically, saccades to the color singleton preceded
saccades to the less salient shape singleton on the majority of trials. This
demonstrates that the order of attentional object selection is largely determined
by stimulus salience when task relevance is equated.
PMID- 29949119
TI - Quality assurance of ultrasound systems: current status and review of literature.
AB - Diagnostic ultrasound (US) images can be obtained from a quality device, in
optimal working conditions, combined with the capable actions of the operator in
tweaking the equipment's characteristics. The quality assurance (QA) is the topic
of this review article, and it is addressed in an US practice through proper
selection of the equipment when purchasing, and through care and preventive
maintenance of the machine for ensuring accurate performance. For optimal US
system functioning, QA steps carried out on the basis of a scheduled program are
needed in any US practice or department. It is critical to confirm in a
semiannual or annual basis that the image quality is maintained according to
standards and any subtle change in equipment's functioning is detected and
amended at an early stage. The use of test objects (also called US testing
phantoms) is required above the basic level of QA testing. The scope of this
review article is to inform the US user about necessary QA knowledge and at the
same time, present the state of the art of the most suitable test methods for US
QA. We referred to relevant publications, selected after performing a systematic
literature search of the MEDLINE, EMBASE and COCHRANE databases, and also to the
standards established by authoritative international societies.
PMID- 29949120
TI - Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE as a promising
treatment of malignant insulinoma: a series of case reports and literature
review.
AB - INTRODUCTION: Insulinomas are a rare type of pancreatic neuroendocrine tumours
characterized by insulin hypersecretion. They are considered malignant when
metastases are present. Traditional therapies often promote only temporarily
symptomatic relief and may be associated with severe adverse effects. There is
scarce experience in treating malignant insulinomas with peptide receptors
radionuclide therapy (PRRNT). PATIENTS AND METHODS: We describe PRRNT results in
four patients with inoperable malignant insulinomas with poorly controllable
hypoglycaemia. All patients received therapy with 177Lu-DOTA-TATE after
conventional therapies failed in controlling disease progression and symptoms.
The activity administered per cycle was 4.8-7.4 GBq. The interval between cycles
was 10-16 weeks. Haematology, liver and kidney function tests were performed
before treatment initiation and 5 and 10 weeks after each cycle. RESULTS: Patient
1 presented significant clinical benefit for 13 months after PRRNT, with imaging
improvement. Patient 2 obtained reduction of the number and severity of
hypoglycaemic episodes during 15 months after therapy. Patient 3 is asymptomatic
since PRRNT first cycle performed 23 months ago and revealed significant imaging
improvement. Patient 4 had resolution of hypoglycaemia only 3 days after PRRNT
first cycle and today, 16 months after therapy, the disease seems to be in
remission and the patient maintains euglycaemic state. PRRNT was well tolerated,
with only hematologic grade 2 toxicity in patient 1 and mild kidney toxicity in
patient 3. CONCLUSIONS: After the start of 177Lu-DOTA-TATE all patients achieved
hypoglycaemia symptomatic control and had evident improvement of their quality of
life. Three patients showed imagiological improvement suggesting reduced tumour
load.
PMID- 29949121
TI - High-dose intravenous methylprednisolone therapy in patients with Graves'
orbitopathy is associated with the increased activity of factor VIII.
AB - PURPOSE: Venous thromboembolic events (VTE), with their life-threatening
manifestation as pulmonary embolism, are potential adverse effects of intravenous
methylprednisolone (IVMP) pulse therapy, partially due to a hypercoagulable
state. The aim of the study was to analyze the influence of IVMP on selected
hemostatic parameters in patients with moderate-to-severe Graves' orbitopathy
(GO). METHODS: 26 euthyroid patients with GO were treated with 12 pulses of IVMP
(6 * 0.5, 6 * 0.25 g every week). Hemostatic variables [factor (F) II, FV, FVII,
FVIII, fibrinogen, antithrombin, activated partial thromboplastin time (aPTT),
prothrombin time, international normalized ratio of prothrombin time, platelets
and D-dimer] were analysed before, 24 and 48 h after 1st, 6th and 12th pulse.
RESULTS: A constant, transient trend in changes of some hemostatic variables was
observed after all assessed pulses. We discovered an increase in median activity
of FVIII 24 and 48 h after pulses, with a shortening of aPTT 24 h after each IVMP
pulse (p < 0.00005). FVII decreased 24 h after each pulse (p < 0.0005 after 1st
and 12th, p < 0.00005 after 6th). Fibrinogen level decreased 48 h after each
pulse (P < 0.00005). We did not observe any statistically significant changes in
hemostatic parameters in the long-term evaluation. Therapy was concluded in one
patient after the 9th pulse due to pulmonary embolism. CONCLUSIONS: The increase
of FVIII activity is a consequence of treatment with IVMP and occurs after each
pulse. In patients with additional risk factors of VTE, anticoagulation
prophylaxis should be considered.
PMID- 29949122
TI - Optimized Pitfall Trap Design for Collecting Terrestrial Insects (Arthropoda:
Insecta) in Biodiversity Studies.
AB - Pitfall traps are commonly used for the collection of terrestrial insects in
ecology and biology studies; they are relatively straightforward to manufacture
and there is a large variety of models described in the literature. However, they
present a few drawbacks: (i) the removal and transport of the collected material
are not practical; (ii) they have low resistance and durability; (iii) they fail
to correctly protect the attractive bait against adverse weather conditions and
scavengers, and (iv) evaporation of the liquid used inside the trap. We proposed
an optimized pitfall trap design for terrestrial insect collection made from
cheap and easily accessible materials. The new design allows the transfer of the
collected material to the lab by removing only that part of the trap where the
insects have been captured; the other part remains in its original place. Thus,
the proposed trap allows easier operation since there is no need to transport
water to replenish the traps after each transfer; in addition, there is less
volume and weight to be carried. The trap can remain in the field for months
because of the durability of its material. Furthermore, the collected material is
better protected against adverse weather conditions and scavengers. Currently, an
efficient and rapid sampling strategy in the field is of global interest to
understand mechanisms that can contribute to the monitor changes in phenology,
succession, and biodiversity.
PMID- 29949123
TI - Population Development of the Invasive Species Thaumastocoris peregrinus
(Hemiptera: Thaumastocoridae) on four Eucalyptus Species of the Subgenus
Symphyomyrtus.
AB - Thaumastocoris peregrinus Carpintero & Dellape (Hemiptera: Thaumastocoridae) is a
small sap-sucking insect that feeds on Eucalyptus L'Her. leaves. Although it is
native to Australia, it currently has a global distribution and it is considered
as one of the big five pests of eucalypts around the world. We described the
development of T. peregrinus population on four Eucalyptus species under the
environmental conditions in Argentina. We also analyzed the use of yellow sticky
traps as a monitoring method for this pest. The four Eucalyptus species were
suitable for T. peregrinus. A cyclic pattern was observed in the development of
the bronze bug population with an annual seasonal peak followed by a decrease in
the abundance, reaching a minimum value during the unfavorable seasons. During
the fall and winter seasons, epizootic events were registered in all the
Eucalyptus species, caused by an entomopathogenic fungus. None of the
meteorological variables had a clear influence neither on the bronze bug
population nor with the occurrence of fungal infection. We found a significant
relationship between the number of nymphs and adults of T. peregrinus in branches
and the number of individuals caught in traps, suggesting that traps give actual
information about the bronze bug abundance in the tree canopy.
PMID- 29949124
TI - Pollen Types Used by the Native Stingless Bee, Tetragonisca angustula
(Latreille), in an Amazon-Chiquitano Transitional Forest of Bolivia.
AB - Samples of corbicular and stored pollen gathered by Tetragonisca angustula
(Latreille, 1811) in an Amazon-Chiquitano transitional forest during the dry
season were analyzed. The pollen spectrum was established as well as the dynamics
of the relationship between the stingless bee and the surrounding flora. Pollen
samples obtained from three rational hives were subjected to acetolysis and 55
pollen types were identified, the most frequent being from Anadenanthera
(Fabaceae), Chenopodiaceae, and Dydimopanax (Araliaceae). Significant differences
in pollen families used between hives along the months of collection were found
in stored pollen and non-significant differences in corbicular pollen. Mean
values of alpha diversity (H') showed T. angustula as a generalist while beta
diversity qualitatively showed that pollen composition was similar between two
hives both of which differed from the third hive. Pollen types in corbicular and
stored pollen were in general related with richness of flowering plants in the
foraging area; the pollen offer was less diverse than the pollen collected, and a
trend to prefer the collection of pollen from the most abundant flowering species
could be discerned. T. angustula showed polylectic feeding habits and a capacity
to adapt to food availability.
PMID- 29949125
TI - HbA1c presents low sensitivity as a post-pregnancy screening test for both
diabetes and prediabetes in Greek women with history of gestational diabetes
mellitus.
AB - BACKGROUND AND AIM: Women with a history of gestational diabetes mellitus (GDM)
are at increased risk for type 2 diabetes (T2D). It is thus recommended that an
oral glucose tolerance test (OGTT) be performed after delivery. Recently, the use
of glycated haemoglobin A1c (HbA1c) has been proposed as a simpler and faster
method to diagnose glucose disorders. The aim of this study was to investigate
whether HbA1c measurement can replace OGTT in the detection of prediabetes and
T2D in women with a history of GDM. PATIENTS AND METHODS: We studied 1336 women
(35.3 +/- 5.8 years old) with a history of GDM 16.6 +/- 28.2 months after
delivery. All women were evaluated through an OGTT and a simultaneous HbA1c
measurement. American Diabetes Association (ADA) criteria were used for the
assessment of glucose disorders. Sensitivity and specificity of HbA1c were
measured for the prediction of T2D and prediabetes, while Cohen's coefficient of
agreement (k) was calculated. ROC analysis was performed to evaluate the
sensitivity and specificity of HbA1c. RESULTS: Based on OGTT, 725 women (54.3%)
were normal, 406 (30.4%) presented impaired fasting glucose (IFG), 48 (3.6%)
impaired glucose tolerance (IGT), 74 (5.5%) combined IFG+IGT, and 83 presented
with T2D (6.2%). By contrast, using HbA1c as a screening test, 1150 women (94.1%)
were normal, while 49 (4.0%) had prediabetes and 23 (1.9%) T2D. Sensitivity of
HbA1c for the diagnosis of prediabetes was 5.3% in comparison to OGTT,
specificity was 99.2%, while for the diagnosis of T2D, the percentages were 29.6
and 100%, respectively. The consistency in classifying impaired glucose tolerance
between HbA1c and OGTT was 59.7%. Cohen's coefficient of agreement was k = 0.116,
indicating slight agreement. Performing a ROC curve, the optimal value of
distinctive ability of HbA1c was 4.6% in the case of prediabetes, while for
diabetes, it was 5.5%. CONCLUSION: This study provided evidence that HbA1c can
identify fewer women with prediabetes and T2D than OGTT, indicating that HbA1c
cannot be recommended as an alternative post-pregnancy screening method.
PMID- 29949126
TI - Clinical pharmacology of glucagon-like peptide-1 receptor agonists.
AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an important asset in
the armamentarium for the treatment of type 2 diabetes mellitus (type 2 DM).
Incretin failure is a critical etiopathogenetic feature of type 2 DM, which, if
reversed, results in improved glycaemic control. GLP-1 RAs are injectable
peptides that resemble the structure and function of endogenous incretin GLP-1,
but as they are not deactivated by the dipeptidyl peptidase-4 (DPP-4), their half
life is prolonged compared with native GLP-1. Based on their ability to activate
GLP-1 receptor, GLP-1 RAs are classified as short-acting (exenatide twice-daily
and lixisenatide once-daily), and long-acting (liraglutide once-daily and the
once-weekly formulations of exenatide extended-release, dulaglutide, and
albiglutide). Semaglutide, another long-acting, once-weekly GLP-1 RA, was
recently approved by the FDA and EMA. Although all of these agents potently
reduce haemoglobin A1C (HbA1c), there are unique features and fundamental
differences among them related to fasting and postprandial hyperglycaemia
reduction, weight loss potency, cardiovascular protection efficacy, and adverse
events profile. It is imperative that current evidence be integrated and applied
in the context of an individualised patient-centred approach. This should include
not only glucose management but also targeting as many as possible of the
pathophysiologic mechanisms responsible for type 2 DM development and
progression.
PMID- 29949127
TI - Replenishment of vitamin D status: theoretical and practical considerations.
PMID- 29949128
TI - Associations between exercise, bone mineral density, and body composition in
adolescents with anorexia nervosa.
AB - OBJECTIVE: To identify the effect of duration of weight-bearing exercise and team
sports participation on bone mineral density (BMD) and body composition among
adolescents with anorexia nervosa (AN). METHOD: We retrospectively reviewed
electronic medical records of all patients 9-20 years old with a DSM-5 diagnosis
of AN evaluated by the Stanford Eating Disorders Program (1997-2011) who
underwent dual-energy X-ray absorptiometry. RESULTS: A total of 188 adolescents
with AN were included (178 females and 10 males). Using multivariate linear
regression, duration of weight-bearing exercise (B = 0.15, p = 0.005) and
participation in team sports (B = 0.53, p = 0.001) were associated with higher
BMD at the hip and team sports (B = 0.39, p = 0.006) were associated with higher
whole body BMC, controlling for covariates. Participation in team sports (B = -
1.06, p = 0.007) was associated with greater deficits in FMI Z-score. LBMI Z
score was positively associated with duration of weight-bearing exercise (B =
0.10, p = 0.018) and may explain the relationship between exercise and bone
outcomes. CONCLUSION: Duration of weight-bearing exercise and team sports
participation may be protective of BMD at the hip and whole body BMC, while
participation in team sports was associated with greater FMI deficits among
adolescents with AN. LEVEL OF EVIDENCE: Level V, descriptive retrospective study.
PMID- 29949130
TI - Improving the overall sustainability of the school meal chain: the role of
portion sizes.
AB - PURPOSE: This work analyses the meal supply in primary schools in Italy to
highlight new areas of inefficiency upstream of the food chain, regarding the
size of the food portions specified in public tenders. A lack of conformity of
food portions can potentially lead to a double negative externality affecting the
sustainability of school meals: overweight children and food waste. METHOD: Based
on the data contained in the contract between municipalities and school catering
services, the analysis was performed on the portion sizes (in grams) of the main
food products included in the school menu for each regional capital (RC) in
Italy. Data analysis regarded two main aspects: consistency of food portions
within regions and adherence to national standards for childrens. RESULTS: The
results revealed great discrepancies amongst regions and in several cases,
portion sizes significantly larger than the reference values of standard portions
for school catering. The study also profiles RC on the basis of portion sizes,
school meal attendance, and childhood obesity rates. CONCLUSIONS: School meals
have the potential to educate the next generation regarding healthy eating
habits, and thus play a leading role in obesity prevention in children.
Similarly, the educational role of eating at school can contribute to raising
children's awareness about one of the most urgent environmental challenges-food
waste-by introducing the best strategies for waste reduction, reuse, and
recycling. Results have economic, social, health, and environmental implications
and highlight the need to revisit policies to introduce new solutions for more
sustainable and healthy school canteens in Italy. LEVEL OF EVIDENCE: Level V,
descriptive studies.
PMID- 29949129
TI - The relative importance of social anxiety facets on disordered eating in
pediatric obesity.
AB - PURPOSE: Children with obesity demonstrate increased risk for eating disorders
and internalizing psychopathology. Research in adults indicates unique facets of
social anxiety differentially relate to eating pathology. These associations
remain understudied in pediatric samples. The current study evaluated
associations between social anxiety and disordered eating, and tested the
relative importance of distinct social anxiety constructs-fear of negative
evaluation, social anxiety in general situations, and social anxiety in new
situations-for disordered eating in weight-loss treatment-seeking youth with
obesity. METHODS: One-hundred and thirty-five youth (Mage 12.6 years; Range 8-17
years; MBMIz = 2.6) from a multidisciplinary outpatient pediatric obesity clinic
completed questionnaires assessing dimensions of social anxiety and the
Children's Eating Attitudes Test (ChEAT). Dominance analyses were used to
evaluate the relative importance of social anxiety facets associated with ChEAT
subscales. RESULTS: Social anxiety subscales did not correlate with Dieting
scores. Dominance analyses indicated Fear of Negative Evaluation (FNE) evinced
complete dominance, thus, emerging as the most important predictor relative to
other social anxiety components for Body/Weight Concern and Food Preoccupation.
General dominance weights for FNE accounted for more than twice the shared and
unique variance, relative to other independent variables within the Body/Weight
Concern and Food Preoccupation models, respectively. CONCLUSIONS: Unique facets
of social anxiety differentially relate to disordered eating in youth with
obesity. Findings suggest nuanced assessment of anxiety constructs, such as FNE,
in pediatric obesity treatment settings may aid in identifying youth at risk for
disordered eating attitudes and behaviors. LEVEL OF EVIDENCE: Level V, cross
sectional descriptive study.
PMID- 29949131
TI - Disordered eating behaviors and energy and nutrient intake in a regional sample
of Brazilian adolescents from public schools.
AB - PURPOSE: To estimate the prevalence of disordered eating behaviors and the
association with energy and nutrient intake and nutritional status in
adolescents. METHODS: A school-based cross-sectional study was performed
involving a probabilistic sample of 487 teenagers (aged 15-19 years) from public
schools in the Metropolitan area of Rio de Janeiro, Brazil. The Eating Attitude
Test and the Bulimic Investigatory Test Edinburgh questionnaires were applied to
identify abnormal eating patterns and unusual dietary patterns, respectively.
Nutritional status was defined by sex- and age-specific body mass index cutoffs.
Energy and nutrient intake were assessed by a 3-day food record. The association
between variables was assessed by the prevalence ratio and 95% confidence
intervals, Pearson's Chi-square test, and linear regression. RESULTS: The
prevalence of abnormal eating patterns was 7.4% and that of unusual dietary
patterns was 18.9%. Vitamin C intake was higher among girls with abnormal dietary
patterns, with a consequent lower frequency of vitamin C deficiency when compared
to those with normal dietary patterns. Calcium intake was lower in boys with
unusual dietary pattern than in those without this behavior. Excess weight was
associated with the presence of unusual dietary pattern in girls (PR: 2.4, 95% CI
1.6-3.5). CONCLUSIONS: The prevalence of disordered eating behaviors was high,
mainly in those who were overweight. It was associated with lower calcium intake
in boys and with higher Vitamin C intake in girls. LEVEL OF EVIDENCE: Level V,
descriptive studies.
PMID- 29949133
TI - Effect of Deltex-1 on proliferation and differentiation of bone marrow
mesenchymal stem cells into smooth muscle cells.
AB - OBJECTIVE: To investigate the effect of Deltex-1 on proliferation and
differentiation of bone marrow mesenchymal stem cells (bMSCs) into smooth muscle
cells (SMCs). MATERIALS AND METHODS: bMSCs of rat were isolated from bone marrow,
cultured and identified. The effect of Deltex-1 on the proliferation of bMSCs
infected with adenovirus vector pAd/Deltex-1 was detected by cell count kit-8
(CCK-8). The expression of smooth muscle myosin heavy chain (SM-MHC), that is one
of the markers of SMCs in bMSCs without treatment, with Deltex-1 virus infection
or empty virus infection and co-cultured with SMCs, were detected by
immunofluorescence cytochemistry staining, RT-PCR and Western blotting. The same
detection of bMSCs and SMCs without treatment was used as normal control,
respectively. RESULTS: bMSCs of rat were isolated from bone marrow, cultured and
identified. Compared with the control, the results of CCK-8 showed that the
growth of bMSCs infected by Deltex-1 virus was slower, and began to appear more
significant especially at 48 (p<0.05, p<0.01). The results of immunofluorescence
cytochemistry, Real-time PCR and Western blot showed that bMSCs with Deltex-1
virus infection and co-cultured with SMCs significantly expressed SM-MHC, and
weakly expressed Notch-1. CONCLUSIONS: The proliferation of bMSCs with Deltex-1
over-expression could be inhibited and its differentiation into smooth muscle
cells could be promoted.
PMID- 29949132
TI - Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses
in an Australian Rheumatoid Arthritis Population.
AB - INTRODUCTION: In Australia, there is an unmet need for improved treatments for
rheumatoid arthritis (RA). Tofacitinib is an oral Janus kinase inhibitor for the
treatment of RA. To provide an overview of key study outcomes for tofacitinib in
Australian patients, we analyzed the efficacy and safety of tofacitinib in the
Australian subpopulation of global RA phase III and long-term extension (LTE)
studies. METHODS: Data were pooled from the Australian subpopulation of four
phase III studies and one LTE study (database not locked at cut-off date: January
2016). Patients in the phase III studies received tofacitinib 5 or 10 mg twice
daily (BID), placebo (advancing to tofacitinib at months 3 or 6), or adalimumab,
with background methotrexate or conventional synthetic disease-modifying
antirheumatic drugs. Patients in the LTE study received tofacitinib 5 or 10 mg
BID. Efficacy endpoints were American College of Rheumatology (ACR) 20/50/70
response rates, and change from baseline in the Disease Activity Score in 28
joints, erythrocyte sedimentation rate [DAS28-4(ESR)] and Health Assessment
Questionnaire-Disability Index (HAQ-DI) scores. Safety endpoints included
incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs.
AEs of special interest and laboratory parameters were analyzed in the LTE study.
RESULTS: Across phase III studies (N = 100), ACR response rates and improvements
in DAS28-4(ESR) and HAQ-DI scores were numerically greater with tofacitinib vs.
placebo at month 3, and increased until month 12. The results were sustained in
the LTE study (N = 99) after 60 months' observation. In general, the efficacy and
safety profiles of tofacitinib were similar to those of the global RA population.
CONCLUSIONS: In Australian patients with RA, tofacitinib therapy demonstrated
sustained efficacy and consistent safety over >= 60 months' treatment. FUNDING:
Pfizer Inc. TRIAL REGISTRATION NUMBERS (ALL CLINICALTRIALS.GOV): NCT00960440;
NCT00847613; NCT00856544; NCT00853385; NCT00413699.
PMID- 29949134
TI - LncRNA PRNCR1 promoted the progression of eclampsia by regulating the MAPK signal
pathway.
AB - OBJECTIVE: We aimed to explore the expression level and biological function of
lncRNA PRNCR1 in preeclampsia (PE). PATIENTS AND METHODS: 57 PE patients and 57
normal pregnant women were enrolled in this study. The expression level of PRNCR1
in the maternal placenta of PE patients and normal pregnancy was detected by qRT
PCR. The CCK-8 assay was carried out to determine the cell viability after
interference and overexpression of PRNCR1 on trophoblasts. We utilized Western
blot to examine the protein level of PRNCR1. RESULTS: Higher systolic blood
pressure, diastolic blood pressure and urinary protein levels in PE patients were
observed in comparison with those in normal pregnant women, while the neonatal
weight in PE group was markedly lower than that in normal pregnant women. LncRNA
PRNCR1 was overexpressed in PE patients, which was positively correlated with
systolic blood pressure, diastolic blood pressure and urine protein, whereas
negatively correlated with fetal birth weight of PE patients. In addition, the
expression of PRNCR1 in BeWo trophoblast cells was significantly decreased after
the interference with PRNCR1, while the cell viability increased. However,
overexpression of PRNCR1 in HTR-8 cells significantly reduced the viability of
cells. Expression levels of p-p38 and p-JNK in PE patients were higher than those
in normal pregnancy women, and the expression level of p-ERK was decreased, which
suggested that PRNCR1 promoted the progression of PE by modulating the MAPK
signaling pathway. CONCLUSIONS: PRNCR1 is highly expressed in PE and promotes the
progression of PE by modulating the MAPK signaling pathway.
PMID- 29949135
TI - A multi-level drill guide template improves the accuracy of pedicle screw
placement in lumbar spine.
AB - OBJECTIVE: Free-hand technique is widely used in pedicle screw placement for
lumbar spine and generally safe; however, screw malposition still occurs. To
develop a novel multi-level drill guide template for pedicle screw placement in
lumbar spine and evaluate its accuracy. MATERIALS AND METHODS: Twelve lumbar
cadaveric specimens were randomly allocated into guide template group (n=6) and
free-hand group (n=6). Computed tomography (CT) scans were obtained for
reconstruction of three-dimensional (3D) model of each lumbar vertebra, and
further an individual guide template was designed. Then the templates and their
corresponding vertebra were developed by rapid prototyping (RP) technology. With
the guide of the templates, screws were inserted via mini-open Wiltse approach.
The positions of the screws were assessed based on postoperative CT images.
RESULTS: In total, 120 pedicle screws inserted (guide template group: n=60 vs.
free-hand group: n=60). For all 30 vertebras in the guide template group, all pre
designed personalized drill guide templates can be fitted into the facet joints
of each vertebra well. Furthermore, our results revealed a significant
improvement for the guide template group in the accuracy rate (p=0.026).
CONCLUSIONS: Armed with advantages of minimal invasion, enhanced accuracy and
safety, the novel technique of multi-level drill guide template can be properly
applied in pedicle screw placement for lumbar spine and promises to be a
potential option in clinical application.
PMID- 29949136
TI - MicroRNA-409 promotes recovery of spinal cord injury by regulating ZNF366.
AB - OBJECTIVE: To explore the role of microRNA-409 in spinal cord injury (SCI)
recovery and its underlying mechanism. MATERIALS AND METHODS: The mouse SCI model
was first established, and the difference in recovery of grip strength was
detected. MicroRNA-409 expressions in mice tissues from sham operation group and
SCI group were detected by quantitative Real-Time Polymerase Chain Reaction (qRT
PCR). We further increased microRNA-409 level in mice spinal cord by plasmids
transfection. Luciferase activity was detected to verify the direct binding of
microRNA-409 and ZNF366. RESULTS: The grip strength in both groups was
temporarily decreased after surgery, while the grip strength in SCI group was
always remarkably lower than that of the sham operation group since the first
week after the surgery, suggesting the successful construction of mouse SCI
model. MicroRNA-409 expression in the SCI group was gradually decreased from the
postoperative 3rd day, which was remarkably lower than that of the sham group.
Additionally, ZNF366 expression in the SCI group began to increase from the first
day after the surgery, which was markedly higher than that of the sham group.
After injection of exogenous microRNA-409, ZNF366 expression in the SCI group
showed a remarkable decrease compared to that of the sham operation group. We
also confirmed that ZNF366 was the target gene of microRNA-409 by bioinformatics
analysis and luciferase activity assay. CONCLUSIONS: MicroRNA-409 is
downregulated after spinal cord injury. Overexpression of microRNA-409 directly
targets ZNF366 and promotes the recovery of spinal cord injury.
PMID- 29949137
TI - Chemerin affects the metabolic and proliferative capabilities of chondrocytes by
increasing the phosphorylation of AKT/ERK.
AB - OBJECTIVE: The purpose of the present study was to explore the mechanism of
action of the adipokine chemerin in osteoarthritis (OA) by means of an in vitro
OA model. MATERIALS AND METHODS: Primary chondrocytes were isolated from normal
rats. The chondrocytes were stimulated with interleukin 1 beta (IL-1beta, 10
MUg/L) to establish a model of induced OA. Chemerin was administered to cells of
this model. After culture of the chondrocytes in the presence of chemerin for 48
h, the expression of the genes related to OA occurrence and protection, matrix
metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), and matrix
metalloproteinase-13 (MMP-13) was examined. Western blot was then performed to
analyze the phosphorylation of the AKT and extracellular signal-regulated kinase
(ERK) proteins in chondrocytes. RESULTS: Stimulation of chondrocytes with IL
1beta markedly reduced the proliferative capability of chondrocytes. Chemerin (5
MUM) also significantly decreased the proliferative capability of chondrocytes.
The combined administration of IL-1beta and chemerin induced an even greater
reduction in the proliferative capability of chondrocytes. Polymerase chain
reaction (PCR) results showed that both IL-1beta and chemerin reduced the
expression of the protective genes in OA (MMP-1, MMP-3, and MMP-13). Also, the
stimulation with IL-1beta and chemerin significantly enhanced the phosphorylation
of AKT/ERK in chondrocytes. CONCLUSIONS: This adipokine induces changes in the
metabolic and proliferative capabilities of chondrocytes by increasing the
phosphorylation of AKT/ERK, thereby inducing OA or aggravating the symptoms of
OA.
PMID- 29949138
TI - Study on the role of Hsa-miR-382-5p in epidural fibrosis.
AB - OBJECTIVE: To investigate the role and potential mechanism of human serum albumin
(hsa)-micro ribonucleic acid (miR)-382-5p in epidural fibrosis formation after
laminectomy. MATERIALS AND METHODS: Cells were transfected with miR-382-5p mimic
or miR-382-5p inhibitor. Then, 3-(4,5)-dimethylthiahiazol (-z-y1)-3,5-di
phenytetrazoliumromide (MTT) assay was employed to detect the effect of miR-382
5p on proliferation, and Real-time reverse transcription-polymerase chain
reaction (RT-PCR) and Western blotting were used to examine the expressions of
miR-382-5p and fibrosis-related proteins after treatment with transforming growth
factor beta (TGF-beta). Luciferase assay and immunofluorescent staining were done
to confirm whether collagen I A1 is a target of miR-382-5p. RESULTS: MTT assay
demonstrated that miR-382-5p had no significant effect on fibroblast
proliferation. Expressions of miR-382-5p and fibrosis-related proteins were
remarkably increased after TGF-beta treatment. Collagen I A1 was acknowledged as
a target of miR-382-5p. MiR-382-5p mimic statistically enhanced the level of
collagen I A1, and miR-382-5p enhanced the expressions of collagen I A1.
CONCLUSIONS: Increased miR-382-5p promotes epidural fibrosis by increasing
collagen I A1 expression, and miR-382-5p may be a potential novel molecular
target for the treatment of epidural fibrosis.
PMID- 29949139
TI - STEEL participates in fracture healing through upregulating angiogenesis-related
genes by recruiting PARP 1.
AB - OBJECTIVE: To explore the effect of STEEL on fracture healing and its underlying
mechanism. PATIENTS AND METHODS: A total of 31 patients with long bone fracture
and who received reoperation because of bone nonunion, delayed union or healing
disorder in the Wuxi Nine Hospital Affiliated to Soochow University from July
2016 to February 2018 were selected. The bone callus at the fracture site was
collected from each patient during the reoperation. QRT-PCR (Quantitative Real
Time Polymerase Chain Reaction) was used to detect STEEL expression in the callus
tissues of the treatment group (bone nonunion or delayed union) and the control
group. In addition, we measured the number of blood vessels in the fracture
tissues by immunohistochemistry. After the construction of tibial fracture model
in mice, STEEL expression and the total number of blood vessels in the treatment
group (sawing treatment) and the control group (sham operation) were detected,
respectively. For in vitro experiments, CCK-8 (cell counting kit-8) assay was
performed to detect cell proliferation after knockdown or overexpression of STEEL
in the vascular endothelial cells. The binding condition of STEEL and its
interacting proteins were detected by RIP (RNA binding protein
immunoprecipitation), and the binding of PARP 1 [poly (ADP-ribose) polymerase 1]
with gene promoter was observed by ChIP (chromatin immunoprecipitation assay).
Western blot was used to detect the expression level of VEGF (vascular
endothelial growth factor). RESULTS: STEEL expression and the vascular density in
the callus tissues of the treatment group were significantly lower than those of
the control group. Downregulated STEEL remarkably decreased the proliferation
ability of HUVEC cells. Meanwhile, the vascular density was also significantly
decreased in mice with a tibial fracture. Overexpressed STEEL obtained the
opposite results. STEEL could interact with PARP 1 to regulate expressions of
downstream genes. Moreover, STEEL could also promote angiogenesis by elevating
VEGF expression. CONCLUSIONS: We showed that STEEL expression could partly
represent the angiogenesis of fracture sites. Moreover, it promoted angiogenesis
by elevating VEGF expression.
PMID- 29949140
TI - miR-98-TXLNG1 (FIAT)/Sp7 function loop mediates osteoblast mineralization.
AB - OBJECTIVE: To investigate the role of microRNAs (miRNAs) and its mechanism in
osteoblast mineralization. MATERIALS AND METHODS: Real-time polymerase chain
reaction (PCR), Northern Blot, and Western Blot were used to identify the
expression mode of regulators. Overexpression and down-regulation experiments
were carried out to study the role of miR-98 and interactions between regulators.
Bioinformatics calculation and luciferase reporter assay were used to prove the
target gene. Electrophoretic mobility shift assay (EMSA), chromatin
immunoprecipitation (CHIP), and promoter luciferase reporter assay confirmed the
relationship between the regulator and the promoter of miR-98. RESULTS: MiR-98
was up-regulated during osteoblast mineralization. Overexpression of miR-98
promoted osteoblast mineralization. Factor inhibiting activating transcription
factor 4 (ATF4)-mediated transcription (FIAT), a negative regulator of osteoblast
differentiation, was confirmed to be a target of miR-98. As a motivator in
osteoblast mineralization, Sp7 transcription factor 7 (Sp7) promoted miR-98
transcription by a combination on the promoter region. CONCLUSIONS: Our study
showed that miR-98 was an important regulator in osteoblast mineralization and
miR-98 carried out its function through a novel miR-98-FIAT/Sp7 regulatory loop.
It provides new insights into the roles of miRNAs in osteoblast mineralization.
PMID- 29949141
TI - Model research on repairing meniscus injury in rabbits using bone marrow
mesenchymal stem cells and silk fibroin meniscus porous scaffold.
AB - OBJECTIVE: The purpose of this study is to evaluate the histocompatibility and
feasibility of structure and function of bone marrow mesenchymal stem cells
(BMSCs) and silk fibroin meniscus porous scaffolds in repairing meniscus injury
in rabbits. MATERIALS AND METHODS: BMSCs were cultured and identified in vitro,
silk fibroin meniscus porous scaffolds were prepared and the histocompatibility
of porous scaffolds was evaluated via in vitro culture. Silk fibroin-BMSCs porous
scaffolds were implanted into the meniscus defect area of New Zealand white
rabbits as the experimental group, the blank scaffold group without BMSCs, pure
BMSCs group and blank control group were set up with 10 rabbits in each group.
Joint capsules were opened for general observation at 6 weeks and 12 weeks after
operation. The specimens received the HE staining, alkaline toluidine blue
staining, and immunohistochemical staining of Type I and Type II collagen and
S100 protein. RESULTS: In vitro HE staining and SEM observation showed that the
scaffolds showed the sponge-like structure with abundant microporous structure on
the surface and inside, which had a good histocompatibility with BMSCs. At 6 and
12 weeks after operation in experimental group, meniscus-like tissues were found
in the meniscus defect area. HE staining showed the fibrous cartilage-like
structure and obvious collagenous fiber structure around arranged in an orderly
manner. Alkaline toluidine blue staining showed the cartilage-specific
glycosaminoglycan (GAG); Type I and Type II collagen and S100 protein staining
were strongly positive. However, the above changes were not seen in other groups.
CONCLUSIONS: BMSCs and silk fibroin meniscus porous scaffolds have a better
histocompatibility and feasibility of structure and function in repairing
meniscus injury in rabbits.
PMID- 29949142
TI - Aberrant NEK2 expression might be an independent predictor for poor recurrence
free survival and overall survival of skin cutaneous melanoma.
AB - OBJECTIVE: Never in Mitosis (NIMA) Related Kinase 2 (Nek2) is a serine/threonine
protein kinase encoded by the NEK2 gene and is an essential enzyme in cell cycle
progression. In this study, we investigated NEK2 expression profile, its
independent prognostic value in terms of recurrence-free survival (RFS)/overall
survival (OS), and the potential mechanisms of its dysregulation in melanoma.
PATIENTS AND METHODS: A retrospective study was conducted using data from Gene
Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA)-skin
cutaneous melanoma (SKCM). RESULTS: NEK2 was significantly upregulated in
melanoma tissues. NEK2 upregulation independently predicted poor OS (HR: 1.500,
95% CI: 1.092-2.059, p = 0.012) and RFS (HR: 2.213, 95% CI: 1.298-3.772, p =
0.004). NEK2 DNA amplification was common in melanoma (192/366, 52.5%), which was
associated with significantly elevated NEK2 expression. NEK2 expression was
weakly and negatively correlated with its DNA methylation (Pearson's r = -0.29).
Loss of p53 was associated with increased NEK2 expression. CONCLUSIONS: Based on
findings above, we infer that NEK2 expression independently predicts poor
survival of melanoma. Its dysregulation might be related to DNA
amplification/methylation and TP53 mutation.
PMID- 29949143
TI - Long non-coding RNA MALAT1 regulates ovarian cancer cell proliferation, migration
and apoptosis through Wnt/beta-catenin signaling pathway.
AB - OBJECTIVE: Long non-coding RNA (LncRNA) MALAT1 is an important regulatory
molecule in many diseases, especially in ovarian cancer. We aimed at exploring
the function of MALAT1 in ovarian cancer and at clarifying its mechanisms.
PATIENTS AND METHODS: The expression level of MALAT1 in ovarian cancer tissues,
para-carcinoma tissues and ovarian cancer cell lines were analyzed by Real-time
polymerase chain reaction (RT-PCR). The cell proliferation rate was detected by
CCK8 assay in SKOV3 and HO8910 cells. Transwell was used to detect the invasion
and migration activities in SKOV3 and HO8910 cells. The cell cycle distribution
and apoptosis rate were measured by flow cytometry analysis. The expression level
of Dvl2, GSK-3beta, beta-catenin and cyclin D1 were detected by RT-PCR and
Western blot. RESULTS: The relative expression level of MALAT1 was identified to
be aberrantly up-regulated in ovarian cancer tissues and cell lines. The high
expression level of MALAT1 was associated with poor prognosis in ovarian cancer
patients. The down-regulation of MALAT1 inhibited cell proliferation, invasion
and migration, arrested cell cycle progression in S phase and induced cell
apoptosis in ovarian cancer cell lines. Meanwhile, the down-regulation of MALAT1
decreased the expression level of DVL2, beta-catenin and cyclin D1 and increased
the expression level of GSK-3beta in SKOV3 and HO8910 cells. Moreover, the
inhibitory effect of MALAT1 down-regulation in cell invasion and migration was
reversed by SKL2001 activating Wnt/beta-catenin signal pathway and enhanced by
XAV939 inhibiting Wnt/beta-catenin signal pathway. CONCLUSIONS: MALAT1 was
overexpressed in ovarian cancer and associated to the poor prognosis. The down
regulation of MALAT1 inhibited cell proliferation, invasion and migration,
arrested cell cycle progression in S phase and induced cell apoptosis by
restraining the activation of Wnt/beta-catenin signaling pathway in ovarian
cancer cells.
PMID- 29949144
TI - CircHIPK3 is upregulated and predicts a poor prognosis in epithelial ovarian
cancer.
AB - OBJECTIVE: CircRNAs have been recently identified as important regulators in
tumors biological functions. However, the clinical significance of circHIPK3 in
epithelial ovarian cancer (EOC) remains unknown. PATIENTS AND METHODS: The
expression of circHIPK3 in EOC tumor tissues and adjacent noncancerous tissues
was analyzed by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The
association between circHIPK3 expression and clinicopathological factors was
analyzed by using Chi-square test. Kaplan-Meier method and log-rank test were
used to analyze the association of circHIPK3 expression with disease-free
survival (DFS) and overall survival (OS) time of EOC patients. Univariate and
multivariate Cox analysis was also performed. RESULTS: We found that circHIPK3
was higher expressed in EOC tissues and cells compared to adjacent normal tissue
and ovarian epithelium cell line, respectively. Higher circHIPK3 expression
associated with lymph node invasion, FIGO stage, and worse DFS and OS of
patients. Moreover, multivariate Cox analysis showed that higher circHIPK3 was an
independent predictor of DFS and OS in EOC patients. CONCLUSIONS: Thus, circHIPK3
may be a novel biomarker for predicting EOC prognosis.
PMID- 29949145
TI - MicroRNA-155 regulates cervical cancer via inducing Th17/Treg imbalance.
AB - OBJECTIVE: To explore the effect of microRNA-155 on cervical cancer and its
underlying mechanism. PATIENTS AND METHODS: Peripheral blood and cervical cancer
tissues were collected. We used quantitative Real-time polymerase chain reaction
(qRT-PCR) to detect expressions of microRNA-155, SOCS1, Th17-related genes
(RORgammat, IL-17A, IL-21, and IL-22), and Treg-related genes (foxp3, TGF-beta,
IL-10, and IL-35) in peripheral blood and cervical cancer tissues. Western blot
was used to detect protein expressions of RORgammat and foxp3. The proportions of
Th17 and Treg cells in CD4+ T cells were measured by flow cytometry. Moreover, IL
17 expression was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS:
MicroRNA-155 was overexpressed in peripheral blood and cervical cancer tissues of
patients with cervical cancer compared with those of normal controls. Th17
related transcription factors and cytokines in cervical cancer tissues were
remarkably elevated than those of normal controls, including RORgammat, IL-17,
and IL-6. Treg-related transcription factors and cytokines obtained the similar
results. Besides, the proportion of Th17 cells in CD4+ T cells was higher in
cervical tissues than that of normal controls. In vitro experiments suggested
that overexpressed microRNA-155 can inhibit the expression of target gene SOCS1,
promote the differentiation of Th17 and increase levels of IL-17, RORgammat, and
STAT3. CONCLUSIONS: MicroRNA-155 is involved in the occurrence and progression of
cervical cancer via inhibiting SOSC1 expression and inducing Th17/Treg imbalance.
PMID- 29949146
TI - HOTTIP regulates progression of endometrial cancer via activating PI3K/AKT
pathway.
AB - OBJECTIVE: To investigate the possible role of HOTTIP in the pathogenesis of
endometrial cancer (EC) and its underlying mechanism. PATIENTS AND METHODS: 76 EC
tissues and 76 adjacent normal tissues were collected in this study. HOTTIP
expression was detected by qRT-PCR (quantitative Real-Time Polymerase Chain
Reaction), and its relationship with clinical prognosis of EC patients was then
analyzed. The effect of in vitro HOTTIP on proliferation, cell cycle, apoptosis,
colony formation, and migration was examined, respectively. Furthermore, the
impact of HOTTIP on PI3K/AKT pathway was explored. RESULTS: HOTTIP was remarkably
overexpressed in EC patients. The survival rate of EC patients with high
expression of HOTTIP was lower than that of patients with low expression, whereas
the pathological grade and tumor size in high expression group were markedly
higher than those of low expression group. After upregulation of HOTTIP by
lentivirus transfection, the proliferation, colony formation, and migration of EC
cells showed a remarkable increase, whereas cell apoptosis was remarkably
inhibited. In addition, high expression of HOTTIP promoted the EC development by
activating PI3K/AKT pathway. CONCLUSIONS: Overexpressed HOTTIP promotes the
development of endometrial cancer via activating PI3K/AKT pathway.
PMID- 29949147
TI - MiR-203 over-expression promotes prostate cancer cell apoptosis and reduces ADM
resistance.
AB - OBJECTIVE: Extra-cellular signal regulated kinase (ERK)/mitogen activated protein
kinase (MAPK) signaling pathway is widely involved in cell proliferation,
apoptosis, and drug resistance. MAPK kinase 1 (MEK1) is the upstream protein
kinase of ERK that can activate ERK/MAPK signaling pathway. microRNA 203 (MiR
203) down-regulation is found to be associated with prostate cancer pathogenesis.
Bioinformatics analysis showed the complementary targeted relationship between
miR-203 and the 3'-UTR of MEK1 mRNA. This study explored the role of miR-203 in
regulating prostate cancer cell proliferation, apoptosis, and ADM resistance
through affecting MEK1 expression. MATERIALS AND METHODS: Dual luciferase assay
confirmed the targeted relationship between miR-203 and MEK1. MiR-203, MEK1, p
ERK1/2, and B cell lymphoma 2 (Bcl-2) expressions were compared in normal
prostate epithelial cells PrEC, prostate cancer cells PC-3M, and drug resistance
cells PC-3M/ADM. PC-3M, PC-3M/ADM cell apoptosis and proliferation were detected
by using flow cytometry under ADM treatment at IC50 concentration of PC-3M cells.
PC-3M cells were cultured in vitro and divided into four groups, including
microRNA-normal control (miR-NC), miR-203 mimic, small interfere NC (si-NC), and
si-MEK1. RESULTS: MiR-203 targeted and inhibited MEK1 expression. MiR-203 levels
and cell apoptosis were significantly lower, while MEK1, p-ERK1/2, Bcl-2, and
cell proliferation were significantly higher in PC-3M/ADM cells compared to the
PC-3M cells. MiR-203 mimic and/or si-MEK1 transfection significantly reduced
MEK1, p-ERK1/2, and Bcl-2 levels, attenuated cell proliferation, induced cell
apoptosis, and decreased drug resistance. CONCLUSIONS: MiR-203 elevation
suppressed prostate cancer PC-3M cell proliferation, promoted apoptosis, and
weakened ADM resistance through targeted inhibiting MEK1 expression to alleviate
ERK/MAPK signaling pathway and Bcl-2 expression.
PMID- 29949148
TI - Short-term effect of metronomic chemotherapy of low-dose Tegafur on patients with
primary hepatic carcinoma after radiofrequency ablation.
AB - OBJECTIVE: To investigate the therapeutic effect of metronomic chemotherapy with
low-dose Tegafur on patients with primary hepatic carcinoma (PHC) after
radiofrequency ablation (RFA). PATIENTS AND METHODS: PHC patients who underwent
RFA were assigned to RFA + Tegafur group and RFA group, respectively. Patients in
RFA + Tegafur group received metronomic chemotherapy with low-dose Tegafur after
RFA. PHC patients in RFA group only received radiofrequency ablation. Therapeutic
efficacy of the two groups was prospectively analyzed within 18 months after RFA.
Disease control rate (DCR) and progression-free survival (PFS) in both groups
were evaluated. RESULTS: Follow-up data showed that DCR in RFA + Tegafur group
and RFA group at 9 months after RFA was 93.3% and 73.4%, respectively (p=0.038).
Within the 18-month follow-up, median PFS in RFA + Tegafur group and RFA group
was 16.25 months and 12.25 months, respectively (p<0.001). One-year PFS in RFA
group was 53.3%, which was remarkably lower than that of RFA + Tegafur group
(83.3%, p=0.012). Moreover, the prevalence of major complications in the present
study was 13.3%. No treatment-related death occurred in both groups. CONCLUSIONS:
Metronomic chemotherapy with low-dose Tegafur after RFA can slow down tumor
progression and prolong the progression-free survival of PHC patients.
PMID- 29949149
TI - Research on values of GDF-15 level in the diagnosis of primary liver cancer and
evaluation of chemotherapeutic effect.
AB - OBJECTIVE: To investigate the values of growth differentiation factor-15 (GDF-15)
level in the diagnosis of primary liver cancer and evaluation of chemotherapeutic
effect. PATIENTS AND METHODS: 92 patients with liver cancer treated from June
2015 to May 2016 were selected as liver cancer group; 53 patients with benign
liver lesion were selected as benign liver disease group, and 40 healthy subjects
receiving physical examination were selected as healthy control group. Fasting
venous blood was drawn from objects of study in the early morning at 1 d after
admission and at the last day after chemotherapy (liver cancer group), and the
serum GDF-15 level was measured. RESULTS: The serum GDF-15 levels in patients in
liver cancer group and benign liver disease group were significantly higher than
those in healthy control group and benign liver disease group (p<0.05). The serum
GDF-15 levels in patients with stage III and IV liver cancer were significantly
higher than those in patients with stage I and II liver cancer, and the serum GDF
15 level in patients with stage IV liver cancer was significantly higher than
that in patients with stage III liver cancer (p<0.05). There was no significant
difference in serum GDF-15 level among patients with different clinical data
(p>0.05). The ROC curve analysis showed that the threshold value of GDF-15 was
1573.23 ng/L, and the sensitivity, specificity, and accuracy were 81.23%, 83.99%,
and 83.62%, respectively. The serum GDF-15 level in patients with progressive
disease was significantly higher than those in patients with partial remission
and stable disease, and the serum GDF-15 level in patients with stable disease
was significantly higher than that in patients with partial remission (p<0.05).
CONCLUSIONS: The serum GDF-15 level has certain clinical values in the diagnosis
of primary liver cancer and evaluation of chemotherapeutic effect.
PMID- 29949150
TI - Evaluation of magnetic resonance imaging in staging of rectal cancer and its
relationship with P16 expression.
AB - OBJECTIVE: To explore the use of magnetic resonance imaging (MRI) in the staging
of rectal cancer and its relationship with p16 expression. PATIENTS AND METHODS:
A total of 75 patients with rectal cancer treated in Oncology Department of our
hospital from March 2013 to March 2017 were randomly included in this study. The
entire pelvis was scanned by MRI, and clinicopathological staging was diagnosed.
Subsequently, all patients underwent total mesorectal excision (TME).
Histopathological gold standard [hematoxylin-eosin (HE) staining] was used to
determine the stage. Immunohistochemistry (IHC) was adopted to detect the
expression of p16 in cancer tissues and cancer-adjacent tissues. Compared with
the results of the pathological examination, the accuracy of MRI diagnosis was
analyzed. The relationship between p16 expression and MRI diagnostic materials
was analyzed. RESULTS: Compared with the results of the pathological examination,
the total accuracy of MRI in the evaluation of T staging was 76.0% (57/75), and
the excessive staging rate and insufficient staging rate were 8.0% (6/75) and
16.0% (12/75), respectively in the assessment of tumor T staging. IHC indicated
that the positive expression rate of p16 in the tumor tissues was significantly
lower than that in the tumor-adjacent tissues [34.67% (26/75) vs. 85.33% (64/75),
p<0.05]. The chi-square test showed that the expression of p16 in the tumors was
notably correlated with T staging, N staging, and myometrial invasion diagnosed
with MRI. CONCLUSIONS: P16 is significantly deficient in the rectal cancer
tissues. MRI examination and identification are helpful for clinical diagnosis of
rectal cancer staging. The combination of the two items may be helpful for the
diagnosis of clinical rectal cancer staging and the establishment of reasonable
treatment regimens.
PMID- 29949151
TI - The long noncoding RNA BC0209135 inhibits the cell invasion through Wnt/beta
catenin signaling in colorectal cancer.
AB - OBJECTIVE: Previous studies have shown that BC029135, a long noncoding RNA
(lncRNA) with high conservation, was decreased with high fold change in
colorectal cancer (CRC) by using microarray assay. In the present work, we
investigated the functions of BC029135 in CRC, as well as the potential
mechanisms underlying the malignant phenotype caused by loss of BC029135.
MATERIALS AND METHODS: Bioinformatics analysis of lncRNA BC029135 was performed
to identify the potential function. The cell lines of HCT-116, SW480, SW620,
LoVo, SW1116, and HT29 were used in this study. The mRNA expression of BC029135
and beta-actinin was measured by Real-Time Polymerase Chain Reaction (RT-PCR).
Western blot analysis was used to determine protein expression of beta-actinin,
MMP-2, cyclin D1, and c-Myc. RESULTS: Our research showed that the expression of
BC029135 in CRC tissues and cell lines was significantly lower than in adjacent
normal tissues. In addition, overexpression of lncRNA BC029135 could inhibit the
invasion of CRC cells. We also found that lncRNA BC029135 inhibits Wnt/beta
catenin signaling in CRC cell lines. CONCLUSIONS: We suggest that up-regulation
of BC029135 suppresses CRC invasion and inactivates Wnt/beta-catenin signaling.
It will provide new insights for the treatment of colorectal cancer and new clues
for clinical treatment.
PMID- 29949152
TI - Effects of miR-223 on colorectal cancer cell proliferation and apoptosis through
regulating FoxO3a/BIM.
AB - OBJECTIVE: Colorectal cancer is a common malignant tumor of the digestive tract.
It frequently occurs at the junction of the rectum and sigmoid colon. It is
characterized by high mortality and poor prognosis. Bcl-2 interacting mediator of
cell death (BIM) plays a role in the regulation of cell proliferation and
apoptosis, and involves in the pathogenesis of colorectal cancer. The
transcription factor forkhead, transcription factor O subfamily 3a (FoxO3a) plays
a role in the regulation of BIM expression and is associated to the pathogenesis
of colorectal cancer. Bioinformatics analysis suggests that there is a targeted
relationship between FoxO3a and microRNA-223 (miR-223). This study aims to
investigate effects of miR-223 on the regulation of FoxO3a/BIM signaling pathway
and colorectal cancer cell proliferation and apoptosis. MATERIALS AND METHODS:
Colorectal cancer cell line SW620 and normal colorectal epithelial cell line
NCM460 were cultured in vitro. Dual luciferase reporter assay was used to
validate the relationship between miR-223 and FoxO3a. Flow cytometry was adopted
to detect apoptosis. EdU staining was applied to test cell proliferation. Western
blot was selected to determine FoxO3a and BIM protein expressions. RESULTS: There
was targeted regulatory relationship between miR-223 and FoxO3a. MiRa-223 up
regulated, FoxO3a and BIM expressions reduced, and cell proliferation was
enhanced in SW620 cells compared with NCM460 cells. MiR-223 inhibitor or pIRES2
FoxO3a transfection significantly increased FoxO3a and BIM expressions,
attenuated cell proliferation, and enhanced cell apoptosis. CONCLUSIONS: MiR-223
targeted inhibited expression of FoxO3. Down-regulating the expression of miR
223, it increased the expressions of FoxO3a and BIM, weakened SW620 cells
proliferation and induced apoptosis.
PMID- 29949153
TI - Study on the function and mechanism of long non-coding RNA DMTF1v4 in the
occurrence of colon cancer.
AB - OBJECTIVE: To investigate the expression of long non-coding RNA (lncRNA) DMTF1v4
in colon cancer, and the relationship between its expression and disease
occurrence. MATERIALS AND METHODS: Human colon cancer tissues and para-carcinoma
tissues were harvested. The expression of lncRNA DMTF1v4 was measured by semi
quantitative PCR. The expression of DMTF1v4 in HT-29 colon cancer cells was
downregulated using siRNA, and the effect of its downregulation on cell growth
was determined by MTT assay and plate clone assay. The effect of DMTF1v4
downregulation on colon cancer cell migration was determined using a transwell
assay and scratch wound assay. The effect of DMTF1v4 on colon cancer cell
apoptosis was determined using Annexin V/PI double-staining. The changes in p
ERK, p-JNK, and p-p38 were measured by Western blot. HT-29 cells with
downregulated DMTF1v4 expression were used to establish the subcutaneous
heterotopic transplantation tumor model in nude mice to study the effect of
DMTF1v4 on tumor growth in animals. RESULTS: Compared with para-carcinoma tissue,
lncRNA DMTF1v4 in colon cancer tissue was highly expressed (p<0.001).
Downregulating lncRNA DMTF1v4 in HT-29 cells showed that lncRNA DMTF1v4 promotes
cell proliferation and migration, and suppresses apoptosis (p<0.05). The effect
of lncRNA DMTF1v4 on the ERK/MAPK signaling pathway was evaluated. The expression
of p-ERK, p-JNK, and p-p38 was increased significantly compared with the control
group (p<0.01). The effect of downregulating DMTF1v4 on tumor growth in animals
showed that tumor growth in nude mice was decreased, and the expression of
apoptosis-related proteins was increased (p<0.01). CONCLUSIONS: The expression of
lncRNA DMTF1v4 is elevated in colon cancer tissues; lncRNA DMTF1v4 promotes colon
cancer cell proliferation and migration, and inhibits apoptosis by downregulating
the expression of p-ERK, p-JNK, and p-p38, thus affecting the progression of
colon cancer. This will provide a basis for the development of new clinical
treatments for colon cancer.
PMID- 29949154
TI - Up-regulation of miR-765 predicts a poor prognosis in patients with esophageal
squamous cell carcinoma.
AB - OBJECTIVE: Up-regulation of miR-765 in esophageal squamous cell carcinoma (ESCC)
has been reported in the previous study. The aim of the present study was to
measure the levels of miR-765 expression in ESCC and evaluate its clinical
significance in ESCC patients. PATIENTS AND METHODS: Quantitative Real-time PCR
assays were performed to analyze the expression of miR-765 in human ESCC tissues
and adjacent esophageal tissues. The relationships between miR-765 expression
levels and the clinical factors were investigated by x2-test. Kaplan-Meier
analysis was performed to evaluate the overall survival (OS) and disease-free
survival (DFS) of ESCC patients with a different expression level of miR-765. The
Cox proportional hazards regression model was used to assess the independent
prognostic factors. RESULTS: The expression level of miR-765 in ESCC tissues was
significantly higher than that in their corresponding normal tissues (p < 0.01).
High miR-765 expression was significantly correlated with tumor stage (p =
0.001), lymph nodes metastasis (p = 0.005), clinical stage (p = 0.007). In
addition, Kaplan-Meier analysis showed that patients with higher miR-765
expression had a significantly poorer OS (p = 0.0010) and DFS (p< 0.0001) than
those with lower miR-765 expression. Multivariate analyses revealed that miR-765
expression served as an independent predictor for both OS (p = 0.001) and DFS (p
= 0.001). CONCLUSIONS: Our findings provided the first evidence that miR-765 may
serve as an indicator for prognosis of ESCC.
PMID- 29949155
TI - LncRNA SNHG16 predicts poor prognosis in ESCC and promotes cell proliferation and
invasion by regulating Wnt/beta-catenin signaling pathway.
AB - OBJECTIVE: Increasing evidence indicated that small nucleolar RNA host gene 16
(SNHG16) acted as a key regulator in the proliferation and metastasis of several
cancers, including esophageal squamous cell carcinoma (ESCC). In this research,
we aimed to explore biological functions, clinical significance and the
underlying molecular mechanisms of SNHG16 in ESCC. PATIENTS AND METHODS: qRT-PCR
was performed to examine the expression of SNHG16 in ESCC cell lines and clinical
ESCC tissue samples. The association of SNHG16 expression with
clinicopathological factors and prognosis was statistically analyzed. Cell
Counting Kit-8, flow cytometry, and transwell invasion assays were performed to
determine the effect of SNHG16 in the regulation of biological behaviors of ESCC
cells. Luciferase assay and Western blot were performed to determine the
activation of Wnt/beta-catenin signaling pathway RESULTS: We observed that SNHG16
expression levels were significantly upregulated in ESCC tissues and cell lines
compared with the corresponding normal tissues and normal esophageal cell line,
respectively. In addition, increased expression of SNHG16 were strongly linked to
tumor stage (p = 0.019), lymph nodes metastasis (p = 0.007) and clinical stage (p
= 0.026). Kaplan-Meier assay showed that the survival time of patients with high
SNHG16 expression was significantly shorter than those with low SNHG16 expression
(p = 0.0017). Univariate and multivariate analyses showed that high SNHG16
expression in ESCC was an independent predictor of poor survival. Loss-of
function experiments revealed that knockdown of SNHG16 suppressed proliferation
and invasion and induced apoptosis of ESCC cells. Mechanistically, Wnt/beta
catenin signaling pathways were actively modulated by SNHG16 in ESCC cells.
CONCLUSIONS: Our findings reveal that SNHG16 plays an important role in ESCC
proliferation/metastasis via modulating Wnt/beta-catenin signaling pathways and
could represent a novel biomarker for predicting poor survival as well a
promising therapeutic target.
PMID- 29949156
TI - MiR-381-3p inhibits proliferation, migration and invasion by targeting LRP6 in
papillary thyroid carcinoma.
AB - OBJECTIVE: MiR-381-3p plays an essential role in the progression of a variety of
cancers, but its expression and role in papillary thyroid carcinoma (PTC)
progression have not been investigated. The aim of this study was to investigate
the expression of miR-381-3p and its function in PTC. PATIENTS AND METHODS: The
expression levels of miR-381-3p and low-density lipoprotein receptor-related
protein 6 (LRP6) mRNA in PTC tissues and cell lines were measured using RT-PCR.
Cell proliferation, migration and invasion were assessed by cell viability assay
and transwell assay. Luciferase assays and Western blotting were performed to
demonstrate miR-381-3p target gene. RESULTS: We found that miR-381-3p was
significantly down-regulated in PTC tissues and cell lines. In vitro assay
indicated that up-regulation of miR-381-3p significantly suppressed PTC cell
proliferation, migration and invasion. Moreover, luciferase reporter gene assay
demonstrated that miR-381-3p could target LRP6 by binding to the 3' UTR. Western
blot and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR)
showed that miR-381-3p overexpression suppressed the expression of LRP6 at both
mRNA and proteins levels. In addition, functional experiment confirmed that LRP6
was involved in the suppressive effect of miR-381-3p-mediated PTC on cell
proliferation, migration and invasion. CONCLUSIONS: Our findings suggested, for
the first time, that miR-381-3p was lowly expressed in PTC tissues, and its up
regulation inhibited tumorigenesis of PTC by targeting LRP6.
PMID- 29949157
TI - MiR-524 inhibits cell proliferation and induces cell apoptosis in thyroid cancer
via targeting SPAG9.
AB - OBJECTIVE: To investigate the effect of miR-524 on the proliferation of thyroid
cancer and its underlying mechanism. PATIENTS AND METHODS: MiR-524 expression
levels in thyroid cancer samples and para-cancer tissues were tested by
quantitative Real-time polymerase chain reaction (qRT-PCR). Cells proliferative
ability and apoptosis were evaluated through methyl thiazolyl tetrazolium (MTT)
and apoptosis assays, respectively. Luciferase reporter assay was used to confirm
the regulatory mechanism. RESULTS: MiR-524 expression was reduced in thyroid
cancer specimen (p<0.05). Up-regulated miR-524 expression inhibited the
proliferative ability and enhanced cell apoptosis of thyroid cancer cells. SPAG9
was a target gene of miR-524, and was reversely regulated by miR-524.
CONCLUSIONS: MiR-524 represses thyroid cancer cell proliferation and induces cell
apoptosis via targeting SPAG9.
PMID- 29949158
TI - Gemcitabine and cisplatin for treatment of lung cancer in vitro and vivo.
AB - OBJECTIVE: To evaluate the antitumor activity of gemcitabine (GEM), cisplatin
(DDP) as well as the combination of these two agents in lung cancer cells and
mice. MATERIALS AND METHODS: The cell viability was evaluated by the CCK-8 assay.
Cell apoptosis was measured by flow cytometry assay and Hoechst staining. The
protein expression of VEGF, VEGFR2, Ang II, AT1R, and ACE2 was examined by
Western blotting. The effect of GEM and DDP on tumor growth and survival time was
also measured in lung cancer mice in vivo. RESULTS: The results revealed that
alone or combined administration of GEM and DDP could inhibit the growth, induce
apoptosis and apoptotic body formation of A549 cells compared with control cells,
with the most significance detected in a combination of GEM and DDP
administration. It is indicated that combined administration of GEM and DDP could
delay the progress of tumor formation in nude mice. The cell apoptosis- and
angiogenesis-related proteins expressions were decreased both in A549 cells and
lung cancer mice. CONCLUSIONS: GEM plus DDP can be an option for patients with
lung cancer treatment. However, further prospective evaluation and randomized
trials are to provide more accurate information through clinical trials.
PMID- 29949159
TI - Knockdown of ferroportin accelerates erastin-induced ferroptosis in neuroblastoma
cells.
AB - OBJECTIVE: Ferroptosis is a new-found iron-dependent form of non-apoptotic
regulated cell death (RCD), which is activated on therapy with several antitumor
agents, but the potential mechanism remains unclear. Erastin, exhibiting
selectivity for RAS-mutated cancer cells, induces ferroptosis by increasing iron
and lipid reactive oxygen species (ROS) levels in cell. Ferroportin (Fpn), the
sole iron export protein, participates in the regulation of intracellular iron
concentration. In this study, we investigated the role of Fpn on ferroptosis
induced by erastin in SH-SY5Y cells. MATERIALS AND METHODS: The cell viability
was determined by CellTiter 96(r) AQueous Non-Radioactive Cell Proliferation
Assay kit. The activity of caspase-3 was measured by ELISA kit. qRT-PCR was
performed to examine the mRNA expression of Fpn. Western blot assay was conducted
to examine the expression level of marker proteins. Specific commercial kits were
used to examine the levels of MDA, ROS and iron in cells, respectively. RESULTS:
Ferroptosis was evaluated by intracellular lipid ROS level and iron
concentration. Hepcidin could prevent erastin-induced ferroptosis by degrading
Fpn. Erastin (5 MUg/mL) was observed to induce ferroptosis in neuroblastoma cells
at 6 hours, which was promoted by knockdown of Fpn. The expression of Fpn gene
and protein was decreased in SH-SY5Y cells treated with erastin. After treatment
with erastin, Fpn siRNA transfection in SH-SY5Y cells was able to accelerate
ferroptosis-associated phenotypic changes. Fpn acted as a negative regulator of
ferroptosis by reducing intracellular iron concentration. Knockdown of Fpn
enhanced anticancer activity of erastin. CONCLUSIONS: These results suggested
that knockdown of Fpn accelerated erastin-induced ferroptosis by increasing iron
dependent lipid ROS accumulation, highlighting Fpn as a potential therapeutic
target site for neuroblastoma. Thus, Fpn inhibitors may provide new access for
chemosensitization of neuroblastoma.
PMID- 29949160
TI - MicroRNA-378 acts as a prognosis marker and inhibits cell migration, invasion and
epithelial-mesenchymal transition in human glioma by targeting IRG1.
AB - OBJECTIVE: Glioma is one common intracranial malignancy. Recently, there has been
a large volume of published studies describing the functions of microRNAs as
potential diagnostic markers for glioma. Data from several sources revealed that
miR-378 played crucial roles in multiple tumors. However, much uncertainty still
exists about the functions and underlying mechanism of miR-378. The purpose of
the present work was to evaluate the potential effect of miR-378 and verify its
influence on the function of IRG1 in glioma. PATIENTS AND METHODS: The miR-378
expression was examined in 52 pairs of glioma tissues using quantitative Real
Time Polymerase Chain Reaction (qRT-PCR). Transwell assays were conducted to
detect the capability of glioma cell migration and invasion with different
transfections. Luciferase reporter was used to confirm whether miR-378 could
regulate immune responsive gene 1 (IRG1). Western blot was used to measure the
expressions of EMT-related markers. RESULTS: miR 378 expressions were notably
reduced in glioma cells and tissues in comparison with controls. The declined miR
378 expressions were correlated with the poor OS and worse clinicopathological
parameters of glioma patients. Overexpression of miR-378 repressed glioma cell
epithelial-mesenchymal transition (EMT) and metastasis as well as the tumor
growth rate and tumor size of glioma mice. Additionally, IRG1 was markedly up
regulated in glioma and was confirmed as a direct target for miR 378 in glioma.
CONCLUSIONS: We showed that the suppressive role of miR-378 in glioma, which was
regulated by IRG1, suggested that the miR-378/IRG1 axis may be an effective
target for glioma treatment.
PMID- 29949161
TI - MiR-448 downregulates CTTN to inhibit cell proliferation and promote apoptosis in
glioma.
AB - OBJECTIVE: miRNAs have been confirmed to be related to cell proliferation and
apoptosis. In this study, we detected the potential effect of miR-448 on glioma
cell proliferation and apoptosis. MATERIALS AND METHODS: miR-448 and CTTN
expression levels were detected in glioma cell lines with quantitative reverse
transcriptase-polymerase chain reaction (qRT-PCR). Cells were transfected with
miR-448 mimics and inhibitor by using lipofectamine 2000 respectively. The
proliferative ability of transfected cells was detected via methyl thiazolyl
tetrazolium (MTT) and cell counting kit-8 (CCK8) assays. Cell apoptosis and cell
cycle were tested using flow cytometry. The regulatory correlation between miR
448 and CTTN was explored by bioinformatics analysis and luciferase reporter
assay. RESULTS: Lower expression of miR-448 and higher level of CTTN were
detected in glioma cells. MiR-448 could regulate cell proliferation, cell
apoptosis, and cell cycle. CTTN was negatively regulated by miR-448. CONCLUSIONS:
miR-448 downregulates CTTN to inhibit cell proliferation and promote apoptosis in
glioma, which indicates a potential therapeutic target of glioma.
PMID- 29949162
TI - Effect of the rs1862513 variant of resistin gene on insulin resistance and
resistin levels after two hypocaloric diets with different fat distribution in
subjects with obesity.
AB - OBJECTIVE: Polymorphisms of a single nucleotide in resistin gene (RETN) have been
associated with insulin resistance. We decide to investigate the role of this
polymorphism on insulin resistance and resistin levels after two hypocaloric
diets. PATIENTS AND METHODS: A sample of 361 obese non-diabetic Caucasian was
enrolled. Biochemical evaluation and anthropometric data were measured at the
start of the trial and repeated after 3 months of both diets (Diet P,
Polyunsaturated vs. diet M, Monounsaturated). RESULTS: With both diets and in
both genotype groups, BMI, weight, fat mass, waist circumference, systolic blood
pressure, and diastolic blood pressure decreased. After diet P, insulin levels
(GG vs. GC+CC genotypes) (-1.2+/-3.8 UI/L vs. -0.7+/-2.1 UI/L; p<0.05), HOMA-IR (
0.6+/-1.0 units vs. -0.4+/-0.9 units; p<0.05), total cholesterol (-10.5+/-20.1
mg/dl vs. -6.1+/-15.1 mg/dl; p<0.05) and LDL-total cholesterol (-8.6+/-10.1 mg/dl
vs. -2.2+/-9.1 mg/dl; p<0.05) decreased in subjects with GG genotype. After diet
M, insulin levels (-1.8+/-2.1 UI/L vs. -0.6+/-3.0 UI/L: p>0.05), HOMA-IR (-0.5+/
1.0 units vs. -0.3+/-1.1 units: p>0.05), total cholesterol (-9.5+/-13.1 mg/dl vs.
-4.4+/-8.1 mg/dl; p<0.05) and LDL-total cholesterol (-8.1+/-6.1 mg/dl vs. -2.9+/
9.1 mg/dl; p<0.05) decreased, too. CONCLUSIONS: We suggest that GG genotype of
RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, and LDL
cholesterol secondary to two hypocaloric diet in obese subjects.
PMID- 29949163
TI - Androgen insensitivity syndrome.
AB - OBJECTIVE: We provide a review of the literature about the Androgen Insensitivity
Syndrome (AIS), its onset and associated developmental anomalies and the genetic
alterations causing it. MATERIALS AND METHODS: We searched PubMed with a larger
emphasis on the physiology, genetics and current management of AIS. RESULTS: AIS
is an X-linked recessive Disorder of Sex Development (DSD). It is caused by
mutations of the Androgen Receptor, and their large amount and heterogeneity
(missense and nonsense mutations, splicing variants, deletions, and insertions)
are responsible for the wide spectrum of possible phenotypes of patients, divided
into Partial AIS (PAIS) and Complete AIS (CAIS). Once the clinical and laboratory
investigations have laid the foundation for a diagnostic hypothesis, it is
important to identify the actual karyotype of the individual and search for the
mutation in the Androgen Receptor to diagnose with certainty the syndrome.
Alternatively, in the absence of such evidence, the diagnosis should more
properly be an AIS-like condition, which we describe as well in our report.
CONCLUSIONS: The management of this DSD is based on pharmacotherapies, surgery
and psychological support: all of them must be directed to facilitate the
patient's life, considering his/her sexual identity.
PMID- 29949164
TI - Apelin-12 exerts neuroprotective effect against ischemia-reperfusion injury by
inhibiting JNK and P38MAPK signaling pathway in mouse.
AB - OBJECTIVE: Cerebral ischemia is a common neurological disease, and its
pathological process remains elusive. This study focused on the protective
mechanism of Apelin-12 protein on the nervous system of mice during cerebral
ischemia-reperfusion injury through JNK and P38MAPK signaling pathway. MATERIALS
AND METHODS: The mouse model with an ischemia-reperfusion injury in middle
cerebral artery was prepared by the modified thread-occlusion method and divided
into 4 groups randomly. Before implantation of the mice, we assessed the
neurological function and evaluated the cerebral edema by the wet-dry weight
method. Lactate dehydrogenase (LDH) kit was used to assess the degree of cell
injury. Malondialdehyde (MDA) kit was used to measure the level of neuron MDA.
Immunohistochemistry was performed to evaluate the neuronal cell in the ischemic
brain. Protein expressions of JNK and P38MAPK and apoptosis-related molecules,
including Bax, Bcl-2, caspase-3, and cleaved caspase-3, were measured by Western
blot assay. RESULTS: After focal cerebral ischemia-reperfusion, a significant
decrease in neurobehavioral score, brain edema and neuron injury in mice
occurred. Apelin-12 significantly improved the neurobehavioral score of the mice
with ischemia-reperfusion injury, alleviated brain edema and the damage to
neurons. In addition, Apelin-12 inhibited the morphological changes and apoptosis
of neuronal cells in the ischemic penumbra of mice. Apelin-12 could downregulate
the expression of Bax and caspase-3, inhibit the activity of caspase-3 and
upregulate the expression of Bcl-2, an anti-apoptotic protein. A significant
reduction in the protein expression of p-JNK and p-p38 was observed in the Apelin
12 group compared with that in the I/R or Vehicle group (p<0.05). CONCLUSIONS:
When an ischemia-reperfusion injury occurred, Apelin-12 can inhibit the JNK and
P38MAPK signaling pathway of the apoptosis-related MAPKs family, thus offering
protection to neurons.
PMID- 29949165
TI - The ten commandments of liver ablation: expert discussion and report from
Mediterranean Interventional Oncology (MIOLive) congress 2017.
AB - Percutaneous liver ablation has become a cornerstone of the recently developed
subspecialty of radiology - that is, interventional oncology. Thermal ablation
technology has evolved rapidly during the past decades, with substantial
technical and procedural improvements that can help obtain better clinical
outcomes and safety profiles. Due to the widespread use of percutaneous ablation,
a comprehensive review of the methodologic and technical considerations seems to
be mandatory. This article summarizes the expert discussion and report from
Mediterranean Interventional Oncology Live Congress (MIOLive 2017) that was held
in Rome, Italy, integrating evidence-reported literature and experience-based
perceptions, to assist not only residents and fellows who are training in
interventional radiology but also practicing colleagues who are approaching to
this locoregional treatment.
PMID- 29949166
TI - Effects of TNF-alpha in rheumatoid arthritis via attenuating alpha1 (I) collagen
promoter.
AB - OBJECTIVE: To explore the role of TNF-alpha in the peripheral blood of patients
with rheumatoid arthritis (RA) and its underlying mechanism. PATIENTS AND
METHODS: 32 patients diagnosed with RA in our hospital from July 2016 to March
2017 were selected in the experimental group. Meanwhile, 32 normal healthy people
were selected in the healthy control group and 21 patients with other autoimmune
diseases in the same period were selected in the disease control group. Serum
samples of the subjects in the experimental group and the control group were
collected. The content of serum tumor necrosis factor-alpha (TNF-alpha) was
detected by enzyme-linked immunosorbent assay (ELISA), and the correlation
between TNF-alpha and RA activity was analyzed. We then constructed rat RA model.
The effect of different doses of TNF-alpha on the RA progression was evaluated by
measuring the foot paw thickness of both hind limbs of rats. Fibroblast-like
synoviocytes (FLS) were treated with different concentrations of TNF-alpha
cytokine in vitro. Cell counting kit-8 (CCK-8) assay was carried out to detect
the cell viability after TNF-alpha treatment. Serum levels of VEGF (vascular
endothelial growth factor) and hydroxyproline were detected. Moreover, the alpha1
(I) collagen overexpression recombinant was constructed and transfected into MH7A
cells. The activation of alpha1 (I) collagen promoter was reflected by the CAT
reporter gene activity. RESULTS: ELISA results showed higher content of TNF-alpha
in the peripheral blood of the experimental group than that of the control group.
In the RA rat model, the foot paw thickness of the hind limbs was increased with
the increase of TNF-alpha concentration. CCK-8 and colony formation assay
demonstrated that the proliferation of MH7A cells was elevated after TNF-alpha
treatment. Higher levels of VEGF and IL-6 secreted by FLS and decreased collagen
synthesis ability of MH7A cells were found after TNF-alpha treatment.
Transfection of the alpha1 (I) collagen overexpression recombinant in MH7A cells
led to the reduced activity of CAT after TNF-alpha treatment, suggesting that the
activation of alpha1 (I) collagen promoter was inhibited. CONCLUSIONS: TNF-alpha
participates in RA by inhibiting the activation of the promoter of alpha1 (I)
collagen, as well as enhancing the secretion of VEGF and IL-6 in MH7A cells.
PMID- 29949167
TI - Global seasonal occurrence of middle east respiratory syndrome coronavirus (MERS
CoV) infection.
AB - OBJECTIVE: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an evolving
global health crisis. Despite recent efforts, there are numerous notable gaps in
the understanding of MERS-CoV seasonal diversity. We aimed at investigating the
global seasonal occurrence of Middle East Respiratory Syndrome coronavirus (MERS
CoV) outbreaks. MATERIALS AND METHODS: We obtained the data on the prevalence and
occurrence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection
from the World Health Organization (WHO) for all the MERS cases reported from the
various countries and their allied ministries. We also recorded the research
documents published in various global scientific journals on the seasonal
occurrence of MERS-CoV infection during the period 2012-2017. RESULTS: Worldwide
2048 laboratory confirmed cases of MERS-CoV infection were reported from June
2012 to the Dec 2017. 1680 (82.03%) cases were from the Saudi Arabia and 368
(17.96%) cases were reported from the other countries of the world. The maximum
number of cases reported in June was 474 (23.14%). 287 (14.01%) cases were
reported from Saudi Arabia and remaining 187 (9.13%) cases were reported from all
over the world. The number of cases reported from April to June was 396 (19.33%)
while the cases encountered from October to December were 231 (11.27%).
CONCLUSIONS: The highest global seasonal occurrence of Middle East Respiratory
Syndrome coronavirus-MERS-CoV outbreak cases were found in the month of June,
while the lowest was found in the month of January during the period of 2012 to
2017. The pattern of MERS-CoV infections has been observed to have seasonal
variations. It is suggested that the health officials should highlight the
seasonal occurrence of MERS-CoV outbreak and take better preventive measures to
minimize the disease burden nationally and globally.
PMID- 29949168
TI - Relationship of platelet microparticle CD62P and activated GP IIb/IIIa with
hypercoagulable state after atrial fibrillation radiofrequency catheter ablation.
AB - OBJECTIVE: The morbidity of atrial fibrillation (AF) is 1%-2% in clinic.
Radiofrequency catheter ablation (RFCA) is a type of radical interventional
therapy for AF, whereas it may lead to a hypercoagulable state. This study
evaluated platelet particle CD62P and platelet activation biomarker GP IIb/IIIa
expressions in AF patients treated by RFCA, and aimed to analyze their
relationships with the hypercoagulable state after RFCA. PATIENTS AND METHODS: A
total of 60 AF patients received RFCA in our hospital were enrolled. The patients
were divided into group A as hypercoagulable state group and group B as non
hypercoagulable group. Healthy volunteers were selected as normal control. Serum
D-Dimer, parathyroid activity index 1 (PAI-1), and tissue plasminogen activator
(t-PA) content were tested by using enzyme-linked immunosorbent assay (ELISA),
while peripheral CD62P and GP IIb/IIIa expressions were detected by using flow
cytometry before, after, and seven days after RFCA. RESULTS: D-Dimer and PAI-1
levels increased, while t-PA reduced in group A compared with that in group B and
control (p<0.05). D-Dimer and t-PA contents gradually elevated, whereas t-PA
level gradually declined in group A before, after, and seven days after RFCA
(p<0.05). Serum CD62P and GP IIb/IIIa expressions in group A were significantly
higher compared to that in group B and control (p<0.05). CD62P and GP IIb/IIIa
levels were significantly higher seven days after RFCA compared with immediate
after RFCA in group A (p<0.05). CD62P showed a positive correlation with GP
IIb/IIIa in hypercoagulable state patients after RFCA (p<0.05). CONCLUSIONS: AF
patient may appear in hypercoagulable state after RFCA. CD62P and GP IIb/IIIa
significantly increased and exhibited a positive correlation.
PMID- 29949169
TI - S100A8/A9 promotes MMP-9 expression in the fibroblasts from cardiac rupture after
myocardial infarction by inducing macrophages secreting TNFalpha.
AB - OBJECTIVE: Inflammation and extracellular matrix degradation play a role in
cardiac rupture (CR) after myocardial infarction (MI). It has been found that the
expression of inflammatory cytokine S100A8/A9 was elevated in acute MI patients,
whereas its impact in CR after infarction remains unclear. PATIENTS AND METHODS:
Samples from cardiac tissue and peripheral blood of patients with CR after MI,
MI, patients without CR, and healthy control (cardiotrauma) were collected to
test the expressions of S100A8/A9, p-p65, and MMP-9. Co-culture system for HCF
cells and macrophages were established to identify the impact of hypoxia-ischemia
on the expressions of S100A8/A9 and TNFalpha. S100A9 and/or TNFalpha blocking
agent were applied to examine the effect on macrophages migration, expressions of
S100A8, S100A9, and TNFalpha. Western blot was adopted to determine levels of p
p65 and MMP-9 protein after the inhibition of S100A9 and/or TNFalpha. RESULTS:
Compared with healthy control and non-CR patients, serum S100A8/A9 and MMP-9
levels were elevated in cardiac tissues of CR patients, while S100A8/A9, p-p65,
and MMP-9 were also overexpressed. Hypoxia-ischemia significantly caused the
increasing levels of S100A8/A9 and TNFalpha in macrophages (p < 0.05). The
blockade of S100A9 and/or TNFalpha suppressed the activation and migration of
macrophages. The inhibition of S100A9 expression also decreased the secretion of
TNFalpha in macrophages, while the suppression of TNFalpha showed no significant
impact on S100A8 and S100A9 levels. Downregulation of TNFalpha or NF-kappaB
markedly declined p-p65 and MMP-9 protein levels in HCF cells from co-culture
system or single culture, whereas the blockade of S100A9 only reduced their
expressions in co-cultured HCF cells. CONCLUSIONS: The level of S100A8/A9 was
upregulated in MI patients with CR. S100A8/A9 induced the activation of NF-kappaB
and expression of MMP-9 protein in HCF cells through facilitating secretion of
TNFalpha from macrophages, which may play a role in triggering extracellular
matrix degradation and CR.
PMID- 29949170
TI - Oxidative stress as a possible mechanism underlying multi-hormonal deficiency in
chronic heart failure.
AB - OBJECTIVE: Chronic Heart Failure (CHF) is associated with multi-hormonal
derangement depicting a prevalence of catabolic vs. anabolic axes. Moreover,
thyroid adaption is characterized by the reduced conversion of thyroxine to the
active hormone triiodothyronine. On the other hand, hormones modulate synthesis
and utilization of antioxidant systems. Therefore, hormonal failure can cause
unbalance between reactive radical species and the defenses, resulting in
oxidative stress (OS). OS is well described in CHF, but the relationship with the
hormonal picture is not entirely known. In the present review, we firstly analyze
the mechanisms of ROS production in the heart, discussing animal and human
studies, and focusing on new discovered protective mechanisms such as sirtuins
and fibroblast growth factor 21 (FGF21). The second section is dedicated to the
role of main anabolic axes influencing antioxidant systems. Finally, we present
some data supporting the hypothesis that OS could be the link between hormonal
derangement and clinical outcome of CHF.
PMID- 29949171
TI - Exosomes derived from bone marrow mesenchymal stem cells improve osteoporosis
through promoting osteoblast proliferation via MAPK pathway.
AB - OBJECTIVE: Osteoporosis is the most common bone metabolic disease. Exosome exerts
a crucial role in the development of multiple diseases. The aim of the study was
to investigate the role of exosome derived from bone marrow mesenchymal stem
cells (MSCs) in osteoporosis and its underlying mechanism. MATERIALS AND METHODS:
MSCs were first isolated from rat bone marrow. After the surface antigen of MSCs
was identified by flow cytometry, MSCs-derived exosomes (MSC-Exo) was extracted.
The osteogenic and lipid differentiation abilities of BMSCs were determined by
alizarin red staining and oil red staining, respectively. Quantitative reverse
transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the mRNA
expressions of genes. Cell counting kit-8 (CCK-8) assay was used to detect the
viability of hFOB 1.19 cells. Western blot was used to measure expressions of the
specific surface markers in exosomes and the MAPK pathway-related proteins in
hFOB 1.19 cells. Moreover, cell cycle of hFOB 1.19 was detected by flow
cytometry. RESULTS: We observed a positive identification of surface antigens in
MSCs, which presented good multidirectional differentiation ability. The isolated
MSC-Exo exhibited typical morphology and particle size of exosomes, and the
detection of specific surface labeled protein was positive under an electron
microscope. After co-culture of MSC-Exo and osteoblast cell line hFOB 1.19, we
found that MSC-Exo could promote the proliferation of hFOB 1.19 cells. Moreover,
mRNA and protein expressions of GLUT3 in cells were increased, and the cell cycle
was also promoted. The expressions of related proteins in the MAPK signaling
pathway were found to be promoted. Rescue experiments demonstrated that MSC-Exo
could promote the growth and cell cycle of hFOB 1.19, which were reversed by p
JNK knockdown. CONCLUSIONS: MSC-derived exosomes improve osteoporosis by
promoting the proliferation of osteoblasts via MAPK pathway.
PMID- 29949172
TI - The postoperative effect of sevoflurane inhalational anesthesia on cognitive
function and inflammatory response of pediatric patients.
AB - OBJECTIVE: To investigate the effect of sevoflurane on cognitive function and
inflammatory response of children after general anesthesia at different times.
PATIENTS AND METHODS: Ninety-three pediatric patients who underwent general
anesthesia surgery were enrolled and divided into groups based on time under
general anesthesia: group A (<1 h, n=27), group B (1-3 h, n=36), and group C (>=
3 h, n=30). Changes in cognitive function and serum inflammatory index were
compared. RESULTS: The occurrence of postoperative cognitive dysfunction (POCD)
in group A and B was lower than in group C and the difference was statistically
significant (p<0.05). The levels of caspase-3, TNF-alpha, and IL-6 in the POCD
group at the different time points were significantly higher than in the non-POCD
group and the differences were statistically significant (p<0.05). Caspase-3, TNF
alpha, and IL-6 levels in the POCD group at the different time points
significantly changed and were highest during the recovery period, while there
were no significant changes in the non-POCD group at the different time points.
CONCLUSIONS: The prolonged sevoflurane inhalational anesthesia time (>= 3 h)
enhanced the occurrence of POCD and was related to the expression levels of serum
caspase-3, TNF-alpha, and IL-6.
PMID- 29949173
TI - Isoflurane reduces endotoxin-induced oxidative, inflammatory, and apoptotic
responses in H9c2 cardiomyocytes.
AB - OBJECTIVE: To investigate the protective effects of ISO on cardiomyocyte injury
induced by lipopolysaccharide (LPS) in H9c2 cells. MATERIALS AND METHODS: Cell
viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay. The activities of LDH and CK in the
supernatant of H9c2 cells with different treatments were determined using
colorimetric assays to assess the conversion of pyruvic acid to lactic acid by
LDH and that of triphosphate and creatine to phosphagen by CK. RESULTS: ISO
significantly enhanced cell viability and alleviated the release of lactate
dehydrogenase and creatine phosphate kinase in a dose-dependent manner in H9c2
cells treated with LPS. However, the protective effects of higher doses of ISO
(1.4% and 2.1%) had no significant difference. Thus, 1.4% ISO was selected for
subsequent experiments. ISO inhibited LPS-induced inflammatory responses, as
evidenced by reduced expression of tumor necrosis factor-a, interleukin (IL)
1beta, and IL-6; it also attenuated the activation of nuclear factor (NF)-kB p65,
and the inhibition of NF-kB p65 DNA-binding activity in H9c2 cells. ISO also
suppressed oxidative stress and enhanced antioxidant defense in LPS-treated H9c2
cells, as determined by decreased levels of reactive oxygen species and
malondialdehyde, increased production of glutathione reductase, and enhanced
superoxide dismutase and glutathione peroxidase activities. Moreover, ISO
inhibited LPS-induced H9c2 cell apoptosis, as shown by reduced caspase-3
activity; downregulated expression of the pro-apoptotic procaspase-3, cleaved
caspase-3, and Bax; and upregulated expression of the anti-apoptotic Bcl-2.
CONCLUSIONS: These findings indicate that ISO reduced LPS-induced H9c2 cell
injury via anti-inflammatory, anti-oxidative, and anti-apoptotic activities;
hence, ISO may be an alternative therapy for septic heart injury.
PMID- 29949174
TI - Clinical effects and safety evaluation of dexmedetomidine hydrochloride combined
with etomidate fat emulsion in patients undergoing interventional treatment of
stroke during anesthesia.
AB - OBJECTIVE: Stroke patients are often elderly and afflicted with comorbidities
that can make them more susceptible to surgical complications during anesthesia,
such as respiratory depression. This study examined the clinical effects of
dexmedetomidine hydrochloride combined with etomidate fat emulsion in patients
undergoing interventional treatment of stroke during anesthesia. PATIENTS AND
METHODS: 90 patients with stroke admitted at the Second Hospital of Dalian
Medical University between February 2015 and March 2016 were selected for
interventional treatment in the study. The patients were randomly divided into
three different treatment groups, with 30 patients in each group. Group A
patients were treated with dexmedetomidine hydrochloride, group B patients were
treated with etomidate fat emulsion, and group C patients were treated with
dexmedetomidine hydrochloride combined with etomidate fat emulsion. Mean arterial
blood pressure (MAP), heart rate (HR), wake-up time, and extubation time were
compared and analyzed for the patients of each group at different time points.
RESULTS: MAP and HR of patients in group C were notably decreased after
anesthesia, and were significantly lower than patients in groups A and B
(p<0.05). MAP and HR of the patients in groups A and B did not significantly
change over the different time points. The three groups also did not show
dramatic changes when patients were extubated after 3 min (p>0.05). Further data
on wake-up time, extubation, and spontaneous breathing recovery time among the
patients did not show any significant differences in the three groups (p>0.05).
However, the prevalence of complications in group C was lower than in groups A
and B (p<0.05). CONCLUSIONS: Dexmedetomidine hydrochloride combined with
etomidate fat emulsion in patients undergoing interventional treatment of stroke
during anesthesia has potential value in clinical applications, through the
maintenance of ideal hemodynamics and a reduction in complications.
PMID- 29949175
TI - The effects of a sodium-glucose cotransporter 2 inhibitor on diabetic nephropathy
and serum oxidized low-density lipoprotein levels.
AB - OBJECTIVE: To investigate the effect of an SGLT-2 inhibitor on diabetic
nephropathy and serum oxidized low-density lipoprotein (ox-LDL) levels. PATIENTS
AND METHODS: We randomly divided 126 patients with diabetic nephropathy into the
treatment group and control group. The 63 patients in the treatment group
received an SGLT-2 inhibitor in addition to routine insulin therapy, while the
control group received only insulin to control blood glucose. All laboratory
indexes were recorded before and after treatment with the SGLT-2 inhibitor. The
prognosis of patients was followed-up. Simultaneously, 63 healthy and BMI-matched
in-patients were selected as the healthy control group. Peripheral blood samples
were collected from all groups, and the levels of ROS were measured by ELISA.
RESULTS: Renal function indexes such as urinary protein, creatinine, blood urea
nitrogen, and glomerular filtration rate (GFR) were significantly higher with
SGLT-2 inhibitor treatment compared with the control group (p<0.05). The fasting
blood glucose level was not significantly increased before or after treatment
(p>0.05). The levels of ROS in peripheral blood were significantly lower in the
treatment group than in the control group (p<0.05). Observation at the 1-year
follow-up showed that the average GFR was significantly higher in the treatment
group than in the control group. Furthermore, the proportion of patients with
stage 1-3 chronic kidney disease was significantly higher in the treatment group
than in the control group (p<0.05). CONCLUSIONS: The SGLT-2 inhibitor had a good
therapeutic effect on renal function in patients with diabetic nephropathy,
without having effects on fasting blood glucose. Additionally, it significantly
delayed the progression of nephropathy. It is therefore worth clinical promotion.
PMID- 29949176
TI - Serenoa repens extracts promote hair regeneration and repair of hair loss mouse
models by activating TGF-beta and mitochondrial signaling pathway.
AB - OBJECTIVE: Plenty of plant extracts have been used for treating hair loss. This
study aims to investigate the effects of liposterolic extracts of Serenoa repens
(LSESr) on hair cell growth and regeneration of hair, and clarify the associated
mechanisms. MATERIALS AND METHODS: Human keratinocyte cells (HACAT) were
cultured, incubated with dihydrotestosterone (DHT) and treated with LSESr. Cell
viability was examined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-
tetrazolium bromide (MTT) assay. Hair loss C57BL/6 mouse model was established by
inducing with DHT. Hair growth, density, and thickness were evaluated. Back skin
samples were collected and stained with hematoxylin and eosin (HE) assay. B-cell
lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), cleaved caspase 3 and
transforming growth factor beta2 (TGF-beta2) were examined using Western blot
assay. RESULTS: LSESr treatment significantly increased HACAT cell viabilities
compared to DHT-only treated cells (p<0.05). LSESr treatment post injection of
DHT significantly converted skin color from pink to gray and increased hair
density, weight and thickness compared to DHT-only treated mice (p<0.05). LSESr
treatment significantly triggered follicle growth and decreased inflammatory
response. LSESr treatment significantly decreased TGF-beta2 and cleaved caspase 3
expression of hair loss mouse models compared to that of DHT treated mice
(p<0.05). LSESr treatment significantly enhanced Bcl-2 expression and reduced Bax
expression compared to that of DHT treated mice (p<0.05). Meanwhile, effects of
LSESr were substantial even achieving to the potential of finasteride.
CONCLUSIONS: LSESr promoted the hair regeneration and repair of hair loss mouse
models by activating TGF-beta signaling and mitochondrial signaling pathway.
PMID- 29949177
TI - 3,6-dihydroxyflavone suppresses the epithelial-mesenchymal transition, migration
and invasion in endometrial stromal cells by inhibiting the Notch signaling
pathway.
AB - OBJECTIVE: Endometriosis is a common disease in women of reproductive age.
Characteristics of endometriosis include invasion, metastasis, and recurrence,
which are similar to those of malignant tumors. However, the etiology and
pathogenesis of endometriosis are still not clear. This study aims to explore the
mechanism of 3,6-dihydroxyflavone (3,6-DHF) in the development of endometriosis.
PATIENTS AND METHODS: Primary cultured ovarian ectopic endometrial stromal cells
(OvESCs) were utilized as the in vitro model of endometriosis. OvESCs were
treated with different concentrations of 3,6-DHF. The expressions of proteins
related to epithelial-mesenchymal transition (EMT) and Notch signal pathway were
detected by Western blot. The mRNA expressions of related genes were detected by
quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The viability of
treated cells was detected by transwell assay. The impact of 3,6-DHF on ectopic
lesions was explored after the animal model of endometriosis was successfully
established. RESULTS: With the increased concentration of 3,6-DHF in OvESCs, the
protein and mRNA expressions of E-cadherin were gradually increased, while the
protein and mRNA expressions of N-cadherin, Twist, Snail, and Slug were
decreased. 3,6-DHF treatment inhibited the migration and invasion ability of
OvESCs in a dose-dependent manner. In the endometriosis model of severe combined
immunodeficient (SCID) mice, lesions in the 3,6-DHF treated group were
significantly smaller than those of the control group. The same changes were
found in the endometriosis model of Sprague Dawley (SD) rats. Protein expressions
of Notch1, NICD, and Hes-1 in OvESCs were inhibited by 3,6-DHF in a dose
dependent manner. 3,6-DHF can inhibit the binding of NICD-CSL-MAML complex in
OvESCs, thereby inhibiting the expressions of proteins related to Notch signaling
pathway in vitro. CONCLUSIONS: 3,6-DHF can inhibit the development of EMT,
migration, and invasion of endometrial stromal cells by inhibiting the Notch
signaling pathway.
PMID- 29949178
TI - Therapeutic effect of Bifidobacterium combined with early enteral nutrition in
the treatment of severe acute pancreatitis: a pilot study.
AB - OBJECTIVE: To explore the therapeutic effect of Bifidobacterium combined with
early enteral nutrition in severe acute pancreatitis. PATIENTS AND METHODS: A
total of 60 patients with severe acute pancreatitis admitted from November 2012
to November 2016 were retrospectively analyzed. According to the different
treatment methods, the patients were divided into Bifidobacterium combined with
early enteral nutrition group (experiment group) and early enteral nutrition
group (control group). Serum ALB (albumin), CRP (C-reactive protein), WBC (white
blood cell count) and PCT (procalcitonin) levels in both groups were observed.
The pain relief time, diet recovery time, length of stay, and hospitalization
costs between the two groups, were compared. The APACHE (acute physiology and
chronic health evaluation scoring system) II score and SOFA (sequential organ
failure assessment) score before and after nutritional support were compared
between the two groups. Adverse events and complications were observed as well.
RESULTS: 58 patients recovered and 2 died after treatment. Improvements in
laboratory indicators such as ALB, CRP, WBC and PCT were much better in the
experiment group than the control group (p<0.05). Both the length of days and
hospitalization cost were lower in the experiment group than those of the control
group (p=0.0029, p=0.0435). In the comparison of hospitalization symptoms,
shorter pain relief time and diet recovery time were found in the experiment
group than those in the control group (p=0.0003, p=0.0218). After the treatment,
APACHE II score and SOFA score of the experiment group were also higher than the
control group. No significant differences in adverse events and complications
between the two groups were exerted (p>0.05). CONCLUSIONS: Bifidobacterium
combined with early enteral nutrition can improve the nutritional status of
patients with severe acute pancreatitis in the acute stage, which also enhances
the patient's immune capacity and the body's resistance to disease.
PMID- 29949179
TI - Tumor microenvironment: recent advances in various cancer treatments.
AB - This is a review regarding different types of cancer treatments. We aimed at
analyzing the tumor microenvironment and the recent trends for the therapeutic
applications and effectiveness for several kinds of cancers. Traditionally the
cancer treatment was based on the neoplastic cells. Methods such as surgery,
radiation, chemotherapy, and immunotherapy, which were targeted on the highly
proliferating mutated tumor cells, have been investigated. The tumor
microenvironment describes the non-cancerous cells in the tumor and has enabled
to investigate the behavior and response of the cancer cells to a treatment
process; it consists in a tissue that may have a predictive significance for
tumor behavior and response to therapy. These include fibroblasts, immune cells
and cells that comprise the blood vessels. It also includes the proteins produced
by all of the cells present in the tumor that support the growth of the cancer
cells. By monitoring changes in the tumor microenvironment using its molecular
and cellular profiles as the tumor progresses will be vital for identifying cell
or protein targets for the cancer prevention and its therapeutic purposes.
PMID- 29949180
TI - Lercanidipine and T-type calcium current.
AB - OBJECTIVE: Lercanidipine is a calcium antagonist with no cardiodepressant
activity, long lasting antihypertensive action and reno-protective effect. Our
previous data demonstrated that lercanidipine blocks L-type calcium channels
(CaL). However, no data are available concerning its effects on T-type calcium
channels (CaT). The aim of this study was to evaluate the effect on both CaL and
CaT and the selectivity ratio of R-lercanidipine, S-lercanidipine and RS
lercanidipine. A comparison with other dihydropyridines (amlodipine and
lacidipine) and the CaT blocker mibefradil was also performed. MATERIALS AND
METHODS: In patch-clamped guinea-pig ventricular myocytes, a voltage protocol was
applied mimicking a normal action potential: HP of -90 mV, 200 ms depolarizing
steps to -50/+50 mV. Lercanidipine was tested at concentrations (1-10 uM) able to
block ~ 50% CaL evoked from a HP in the range of -50 to -30 mV. Cells were
superfused with a Na+ and K+ free solution pre-warmed to 35 degrees C to abolish
overlapping currents. RESULTS: Using the described voltage protocol, all
dihydropyridines at 1 uM blocked less than 20% CaL, with the exception of
lacidipine, that reduced CaL >60% of control. All calcium channel blockers (CCBs)
blocked a significant amount of CaT, varying from 28% (mibefradil) to 4.3%
(amlodipine). Based on the ratio between CaT and CaL blockade in each cell (T/L),
mibefradil, as expected, showed the highest T affinity (T/L=1.3). Lercanidipine,
either racemate or enantiomers, showed a noticeable T selectivity, T/L varying
from 1.05 (S-lercanidipine) to 1.15 (R-lercanidipine). CONCLUSIONS: All CCBs
examined in this study showed both T- and L-channel blocking activities and can
be differentiated based on their relative affinity. Among tested
dihydropyridines, lercanidipine showed the highest T/L selectivity.
PMID- 29949181
TI - Endometriosis - insights into a multifaceted entity.
AB - Firstly described at the end of nineteenth century, endometriosis remains an
enigmatic disease, from etio-pathogenesis to specific markers of diagnosis and
its ability to associate with malignancies. Our review has been designed from a
historical perspective and steps up to an updated understanding of the disease,
facilitated by relatively recent molecular and genetic progresses. Although the
histopathological diagnosis is relatively simple, the therapy is difficult or
ineffective. Experimental models have been extremely useful as they reproduce the
human disease and allow the testing of different potential modulators or
treatment options. Due to molecular resemblance to carcinogenesis, applications
of anti-cancer agents are currently under scrutiny. The desired goal of an
efficient therapy against symptomatic disease, along with associated infertility
and malignancies, needs a deeper insight into the complex mechanisms involved in
endometriosis initiation, development, and progres-sion. Current trends in
genomic and proteomic approaches are useful for a more accurate classification
and for the identification of new therapeutic targets.
PMID- 29949183
TI - Does the peer-review process facilitate incivility among nurse scholars?
PMID- 29949182
TI - Reframing and addressing horizontal violence as a workplace quality improvement
concern.
AB - AIM: To reframe horizontal violence as a quality improvement concern. BACKGROUND:
Although the number of studies exploring horizontal violence has increased,
evidence supporting the effectiveness of current interventions is weak and the
problem persists. Often framed as an individual or interpersonal issue,
horizontal violence has been recognized as a complex phenomenon that can only be
understood through an examination of social, individual and organizational
factors. As such, interventions to address horizontal violence must be applied
systemically and address contributions from all sources. DESIGN: This is a
discussion paper. DATA SOURCES: This discussion is based on results of a study of
nurses' perceptions of horizontal violence and review of the literature.
IMPLICATIONS FOR NURSING: Context is recognized as a contributing factor in human
behavior, yet often overlooked in interventions to address horizontal violence.
Moving the focus away from the individual and investigating systems contributions
to horizontal violence using existing quality improvement frameworks is
suggested. CONCLUSION: To date, efforts to address horizontal violence have not
been proven effective. There is a call for a wider application and investigation
of interventions. This reframing provides the system level application suggested
and would address a broader range of factors contributing to the perpetuation of
the phenomenon.
PMID- 29949184
TI - A systematic review of the management and outcomes of cecal and appendiceal
volvulus in children.
AB - AIM: Appendiceal volvulus (AV) and cecal volvulus (CV) are rare conditions and
there is no consensus regarding the best surgical approach. This study reviewed
CV and AV management and outcomes in children. METHODS: PubMed was reviewed from
1990 to 2018 for AV and CV in children and studies published in English were
selected by two independent reviewers. This identified 24 papers that provided
case reports on 29 children (72% male) with a median age of 10 years. RESULTS:
Abdominal distension and abdominal pain were the most common symptoms and seven
children had Cornelia de Lange syndrome. The initial treatment was surgical in 27
cases and endoscopic in 2. In 23 children, variants of cecopexy were performed.
There was no mortality. Complications occurred in seven cases: five with sepsis
and two with enterocutaneous fistulas. There were three CV recurrences and these
were all in cases where cecopexy was not performed. CONCLUSION: AV and CV are
rare paediatric pathologies. Since a quarter of the patients had Cornelia de
Lange syndrome, it is paramount to consider CV when abdominal symptoms occur.
Complications were minor with prompt management. In order to reduce recurrence,
cecopexy is recommended in CV cases and appendectomy in AV cases.
PMID- 29949185
TI - A qualitative exploration of nursing students' perceptions of the homeless and
their care experiences.
AB - The health care needs of the homeless are more complex than those of the
population at large. The purpose of this qualitative study was to explore
undergraduate nursing students' perceptions of the homeless. Thematic content
analysis of responses from 19 undergraduate nursing students yielded four themes
describing student experiences with the homeless, their perceptions of
homelessness and the health care of the homeless, and their suggestions for best
teaching strategies. Students in this study had varying amounts of experience
with and knowledge of the homeless. While our participants strongly believed that
homeless people deserved compassionate, equitable nursing care, many of their
statements suggested an implicit bias toward the homeless. This suggests that
student nurses need more comprehensive education concerning the homeless and the
health care needs of this vulnerable population. Few interventions aimed at
educating student nurses about homelessness and changing their attitudes to
mitigate bias are based on research, particularly research conducted from the
perspective of the homeless, and few explore the impact of civil interactions on
health outcomes. The findings of this study may assist nurse educators in
developing education interventions to improve students' knowledge of
homelessness.
PMID- 29949186
TI - Outcomes of second-line treatment after fludarabine cyclophosphamide and
rituximab in patients with chronic lymphocytic leukemia outside clinical trials.
AB - OBJECTIVE: To evaluate disease characteristics and long-term outcomes in patients
requiring second-line treatment following fludarabine, cyclophosphamide, and
rituximab (FCR), for relapsed/refractory disease (R/R), or following
discontinuation due to toxicities. METHOD: A retrospective analysis of 126
chronic lymphocytic leukemia patients treated with frontline FCR: 63 received
second-line treatment (41 relapsed, nine refractory [SD/PD], 13 prior toxicity).
Time to next treatment (TTNT) was calculated from beginning FCR to initiation of
second-line therapy. Overall and event-free survival was calculated from
initiation of salvage treatment (OS2/EFS2). RESULTS: Median follow-up for the
entire cohort was 67 and 37 months from second-line therapy. TTNT < 24 months was
associated with shorter OS2 and EFS2 similar to those observed with primary
refractory disease (OS2 19 and 23 months; EFS2 12 and 9 months for TTNT < 24
months and SD/PD, respectively). TTNT >= 24 months (71% chemotherapy-based second
line), had longer OS2 and EFS2 (48 and 20 months). Among the 13 patients
receiving second-line therapy after discontinuing FCR due to toxicity EFS2 was 41
months (59 months from initiation of FCR). CONCLUSION: With limitations of sample
size and treatment heterogeneity, patients progressing <24 months following FCR
have poor outcomes, similar to refractory patients, while longer remissions are
indicative of a chemoimmunotherapy sensitive disease. Patients who discontinue
FCR for toxicities may achieve excellent outcomes with subsequent treatment.
PMID- 29949187
TI - Quantitative adiabatic-refocused INEPT (QA-RINEPT) as a tool for fast and
reliable characterization of polyols.
AB - 13 C nuclear magnetic resonance (NMR) is a powerful tool for the detailed
characterization and structure elucidation of polymeric samples. The low natural
abundance and sensitivity of the 13 C isotope, however, lead to very long
acquisition time, therefore limiting the use of such technique. We report here
the implementation of a quantitative method, quantitative adiabatic-refocused
insensitive nuclei enhanced by polarization transfer (QA-RINEPT), for the
characterization of polyol samples. The method, based on the well-known
insensitive nuclei enhanced by polarization transfer sequence, allows the boost
in sensitivity of the carbon resonances without sacrificing the quantitative
aspects of the analysis. This is achieved controlling the polarization transfer
mechanism and introducing a response factor to calculate precisely the
sensitivity gain of the different carbon signals. Compared with the standard
single pulse quantitative experiment, the QA-RINEPT method produces up to 4.7*
signals enhancement per unit of time. An in-depth statistical analysis was
conducted to confirm the reliability of the QA-RINEPT method. We show that there
is excellent agreement between the new and old 13 C-NMR methods for the
quantitative determination of several important polyol properties such as the
comonomer and initiator content as well as the ratio of primary and secondary
hydroxyl groups.
PMID- 29949188
TI - CAR-T cell manufacture: snatching victory when defeat is looming.
PMID- 29949189
TI - Very low rate of anti-D development in male, primarily immunocompetent patients
transfused with D-mismatched platelets.
PMID- 29949191
TI - D blocking phenomenon overcome.
PMID- 29949192
TI - Passing the transfusion torch.
PMID- 29949193
TI - Distributed ledgers in transfusion medicine: an opportunity for standards to
accelerate innovation.
PMID- 29949194
TI - Conservation of O- red blood cells: a fresh look at a shared responsibility.
PMID- 29949195
TI - Serum glutamate was elevated in children aged 3-10 years with autism spectrum
disorders when they were compared with controls.
AB - AIM: This study aimed to see whether measuring serum glutamate in children with
autism spectrum disorder (ASD) could provide a biological marker that could allow
early intervention. METHODS: Serum glutamate was measured in 30 patients aged 3
10 years presenting with ASD to the Abou El Reesh Hospitals, Cairo University,
Egypt and 30 matched controls without ASD in 2015. The Vineland Social Maturity
Scale was applied to assess social competence, self- help skills and adaptive
behaviour in both groups. The severity of autism was measured with the Childhood
Autism Rating Scale test. RESULTS: The patients' group showed higher mean values
of serum glutamate (5.888) than the control group (2.521) and the statistical
difference was significant (p = 0.00021). There was no significant difference (p
= 0.151) in the serum level of glutamate between patients receiving 1-2 mg of
risperidone (6.519 +/- 2.851) and those who were free from any medication for at
least six weeks (5.157 +/- 2.184). CONCLUSION: We found higher levels of serum
glutamate in subjects with ASD and this might reflect altered glutamatergic
neurotransmission which may aid early ASD detection. Further investigations are
needed with a large number of participants to further clarify the possibility of
using glutamate as a biomarker for ASD.
PMID- 29949196
TI - Genetic variants of MGMT, RHPN2, and FAM49A contributed to susceptibility of
nonsyndromic orofacial clefts in a Chinese population.
AB - BACKGROUND: The role of underlying genetic factors in the pathogenesis of
nonsyndromic orofacial clefts (NSOC) remains poorly understood. Although
genomewide association studies (GWASs) of NSOC have successfully identified a
large number of novel genetic risk loci, association results of replication
studies are inconsistent across different populations. METHODS: Six single
nucleotide polymorphisms (SNPs) (rs7922405 at 10q26.3, rs73039426 at 19q13.11,
rs7552 at 2p24.2, rs1788160 at 8q22.2, rs9381107 at 6p24.3, and rs17095681 at
10q25.3) were analyzed for an association with NSOC in 1062 participants of
Chinese descent (596 patients and 466 controls). We applied the multifactor
dimensionality reduction (MDR) method to detect potential gene-gene (G * G)
interactions in the six SNPs. RESULTS: The genotype or allele frequencies of SNPs
rs7922405, rs73039426, and rs7552 showed significant differences between the
controls and patients with NSOC, whereas no association was shown between three
SNPs (rs1788160, rs17095681, and rs9381107) and NSOC. MDR analysis did not reveal
significant G * G interactions for susceptibility to NSOC. CONCLUSION: We
confirmed that three genes (rs7922405 of MGMT, rs73039426 of RHPN2, and rs7552 of
FAM49A) may contribute to NSOC in Chinese populations. MGMT and RHPN2 are
associated with NSOC, which is herein demonstrated for the first time.
PMID- 29949197
TI - The Narrative Circle Model: An interpretative framework for nursing education and
research.
AB - BACKGROUND: A research study entitled "Newly-Graduated Baccalaureate Registered
Nurses, the 21st Century Health Care Environment and Mapping the Landscape for
Curricular Change" explored the perceptions of newly graduated registered nurses
(NGRNs). During the research process, a model for nursing education and research
was revealed and subsequently developed as an interpretative framework. PURPOSE:
Qualitative narrative inquiry research explored the perceptions of newly
graduated registered nurses and shaped the creation of the Narrative Circle Model
for Nursing Education and Research (NCMNER). This paper will explain how the
model represents the cyclic yet reciprocal relationship among education,
research, and practice using narratives. DESCRIPTION: The NCMNER provides a
unique perspective by illustrating knowledge gained from narratives of NGRNs
using narrative inquiry research methodology to influence nursing education and
practice. Ultimately, the model will illustrate the significant implications of
education and research in advancing the future of nursing with educational,
social, and political change. CONCLUSION: Concepts from the NCMNER provided an
interpretative framework for the major findings of the research; specifically,
narratives used in educational curriculum, narratives from research methodology,
and hence the relationships between narratives in education and research.
PMID- 29949198
TI - Death-associated protein kinase (DAPK) family modulators: Current and future
therapeutic outcomes.
AB - Serine/threonine kinases (STKs) represent the majority of discovered kinases to
date even though a few Food and Drug Administration approved STKs inhibitors are
reported. The third millennium came with the discovery of an important group of
STKs that reshaped our understanding of several biological signaling pathways.
This family was named death-associated protein kinase family (DAPK family). DAPKs
comprise five members (DAPK1, DAPK2, DAPK3, DRAK1, and DRAK2) and belong to the
calcium/calmodulin-dependent kinases domain. As time goes on, the list of
biological functions of this family is constantly updated. The most extensively
studied member is DAPK1 (based on the publications number and Protein Data Bank
reported crystal structures) that plays fundamental biological roles depending on
the cellular context. DAPK1 regulates apoptosis, autophagy, contributes to the
pathogenesis of Alzheimer's disease, acts as a tumor suppressor, inhibits
metastasis, mediates the body responses to viral infections, and regulates the
synaptic plasticity and depression. For their biological roles, several DAPKs'
modulators have been reported for treatment of many diseases as well as acting as
probe compounds to facilitate the understanding of the biological functions
elicited by this family. Despite that, the number of reported modulators is still
limited and more research needs to be conducted on the discovery of novel
strategies to activate or inhibit this family. In this report, we aim at drawing
more attention to this family by reviewing the recent updates regarding the
structure, biological roles, and regulation of this family. In addition, the
small-molecule modulators of this family are reviewed in details with their
potential therapeutic outcomes evaluated to help medicinal chemists develop more
potent and selective possible drug candidates.
PMID- 29949200
TI - Personhood: An evolutionary concept analysis for nursing ethics, theory,
practice, and research.
AB - BACKGROUND: The purpose of this concept analysis was to examine how the concept
of personhood has been used in the nursing literature. The person is central to
nursing, as the object of nursing work, or care, and a key element of theory.
Health and illness confront conventional notions of personhood based on the
Western philosophy, in delineating boundaries of life and death, and grappling
with pathophysiological changes and alterations in capacities that challenge our
understandings of what makes a person whole. METHODS: Rodgers' evolutionary
method was selected; it emphasizes the relationship between concepts, language,
and communities of users. A literature search between 1950 and 2017 generated 760
articles; 54 were retained for analysis. RESULTS: Four themes were identified:
(1) personhood and nursing ethics, emphasizing scientific advances, and
establishing criteria; (2) personhood as a morally significant, relational
process realized through nursing care; (3) personhood lost (or neglected); (4)
interventions aimed at understanding, recognizing, and enhancing personhood.
Related terms, antecedent concepts, and consequences are explored. CONCLUSIONS:
This preliminary view of personhood in the nursing literature demonstrated how
the concept has been developed, used, and understood. Areas for future research
include nursing ethics, theory, and clinical practice, as well as links with
other academic disciplines.
PMID- 29949199
TI - Lean non-alcoholic fatty liver disease patients had comparable total caloric,
carbohydrate, protein, fat, iron, sleep duration and overtime work as obese non
alcoholic fatty liver disease patients.
AB - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial
disease that involves a complex interaction between genetics, diet, and
lifestyle. Although closely related with obese subjects, it is also common in
lean humans. This study aimed to characterize the diet and lifestyle of lean and
obese NAFLD patients in China. METHODS: To characterize the diet and lifestyle of
lean and obese NAFLD patients, we conducted a matched case-control study that
included 351 Chinese adults. General characteristics, dietary intake, and
lifestyle were gathered by using a valid and reliable dietary questionnaire. We
compared the dietary intake and lifestyle between lean and obese NAFLD patients.
RESULTS: All NAFLD patients had more total caloric, calorigenic nutrients
(carbohydrate, fat, and protein), grain, potato, fruit, and iron with higher
levels of waist circumference and overtime work but shorter sleep duration than
their corresponding controls. Particularly, lean NAFLD patients consumed
comparable total caloric, calorigenic nutrients, iron, sleep duration, and
overtime work as obese NAFLD patients, though they consumed lower levels of
grain, potato, and fruit (lean NAFLD patients vs. obese NAFLD patients: mean +/-
SD, g/day grain: 291.8 +/- 83.8, 365.2 +/- 89.0; potato: 63.5 +/- 33.1, 80.4 +/-
37.6; fruit: 324.3 +/- 148.4, 414.0 +/- 220.4; P < 0.0001). CONCLUSION: Non
alcoholic fatty liver disease patients had higher total caloric, calorigenic
nutrients, grain, potato, fruit, iron, and overtime work but shorter sleep
duration. Lean NAFLD patients had comparable total caloric, calorigenic
nutrients, iron, sleep duration, and overtime work as obese NAFLD patients. These
features could be used to the nutritional education and therapeutic guidance for
lean NAFLD patients in the future.
PMID- 29949201
TI - Sedation scales: Do they capture the concept of opioid-induced sedation?
AB - AIM: The purpose of this study was to explore the concept of opioid-induced
sedation and how nurses define and measure sedation in the hospital setting.
BACKGROUND: Opioid medications are the primary treatment for acute pain in the
postoperative setting. One of the most serious side effects of opioid therapy is
excessive sedation and respiratory depression. Nurses have the responsibility of
providing effective pain management, while keeping the patient safe from adverse
sedation and respiratory depression. Thus, the assessment of sedation becomes an
integral part of the nurses' responsibilities. REVIEW METHOD: A review of the
literature on the concept of opioid-induced sedation, and how it is measured by
nurses in the hospital setting was performed using the Walker and Avant's (2011)
framework. RESULTS: Sedation is an ambiguous concept that challenges nurse's
critical thinking skills. The linear sedation scales can assist with the
measurement of sedation, but may lack sensitivity and specificity in detecting
the small changes on the continuum of levels of consciousness. Additionally, the
scales may not capture the entire aspects of the concept of sedation.
CONCLUSIONS: Sedation, as defined by the linear sedation scales is limiting
nurses' appreciation of the small changes in level of cognition as well as
consciousness that occurs as an adverse and potentially dangerous side effect of
opioid medications used for acute pain management. Through developing a better
understanding of sedation as a clinical concept, nurses may enhance their
clinical skillset in safer postoperative pain management. Additionally, linear
sedation scales could be further developed to better capture all aspects of
sedation.
PMID- 29949202
TI - Fetal cerebral hemorrhage due to X-linked GATA1 gene mutation.
AB - We report a multiplex family with a GATA1 gene mutation responsible for a massive
fetal cerebral hemorrhage occurring at 36 weeks. Two other stillbirth cousins
presented with fetal hydrops and congenital hemochromatosis' phenotype at 37 and
12 weeks of gestation. Molecular screening revealed the presence of a c.613G>A
pathogenic allelic variation in exon 4 of GATA1 gene in the 3 male siblings and
their carrier mothers. The diagnosis of a GATA1 gene mutation may be suspected in
cases of male fetuses with intracerebral bleeding, particularly if a history of
prior fetal loss(es) and mild maternal thrombocytopenia are also present.
PMID- 29949203
TI - Midface toddler excoriation syndrome (MiTES) can be caused by autosomal recessive
biallelic mutations in a gene for congenital insensitivity to pain, PRDM12.
AB - BACKGROUND: Midface toddler excoriation syndrome (MiTES) is a condition recently
reported in three unrelated children. Habitual scratching from the first year of
life inflicted deep, chronic, scarring wounds around the nose and eyes. One child
had a mild neurological deficit but there was no other evidence of insensitivity
to pain. Bilateral distribution and localization to the midface distinguish MiTES
from other causes of self-inflicted skin damage such as trigeminal trophic
syndrome. An earlier study of five siblings from a consanguineous Irish family,
with lesions corresponding to MiTES plus other sensory deficits, showed
homozygous mutations in a gene for hereditary sensory and autonomic neuropathy
type VIII (HSAN8), PRDM12. OBJECTIVES: To study further cases of MiTES, including
analysis of PRDM12. METHODS: We describe five further children, from four
families, with facial lesions typical of MiTES, in whom mutation analysis of
PRDM12 was carried out. RESULTS: Homozygous or compound heterozygous pathogenic
expansions of the PRDM12 polyalanine tract were found in four of five affected
individuals, in three families. CONCLUSIONS: Our finding of autosomal recessive
mutations in PRDM12 in four of five patients with MiTES extends the phenotypic
spectrum of PRDM12 mutations, which usually cause HSAN8, characterized by
mutilating self-inflicted wounds of the extremities, lips and tongue. By
contrast, MiTES shows severe midfacial lesions with little if any evidence of
generalized pain insensitivity. The condition is probably genetically
heterogeneous, and other congenital insensitivity to pain and HSAN genes such as
SCN11A may be implicated. This new understanding of the nature of MiTES, which
can masquerade as factitious disease, will facilitate appropriate management.
PMID- 29949204
TI - Individual and monitoring centre influences upon anticoagulation control of AF
patients on warfarin: A longitudinal multi-centre UK-based study.
AB - OBJECTIVES: Time within therapeutic INR range (TTR) predicts benefits/risk of
warfarin therapy. Identification of individual- and centre-related factors that
influence TTR, and addressing them to improve anticoagulation control, are
important. This study examined the impact of individual and centre-related
factors upon long-term anticoagulation control in atrial fibrillation patients in
seven UK-based monitoring services. METHODS: Data between 2000 and 2014 on 25 270
patients (equating to 203 220 patient years) [18 120 (71.7%) in general practice,
2348 (9.3%) in hospital-based clinics and 4802 (19.0%) in domiciliary service]
were analysed. RESULTS: TTR increased with increasing age, peaking around 77% at
70-75 years, and then declined, was lower in females than males, and in dependent
home-monitored patients than those attending clinic (P < 0.0001). TTR, number of
dose changes and INR monitoring events and the probability of TTR <= 65%,
differed across the centres (P < 0.0001). CONCLUSIONS: Although all the
participating centres ostensively followed a standard dosing algorithm, our
results indicate that variations in practice do occur between different
monitoring sites. We suggest feedback on TTR for individual monitoring sites
gauged against the average values reported by others would empower the individual
centres to improve quality outcomes of anticoagulation therapy by identifying and
adjusting contributory factors within their management system.
PMID- 29949206
TI - Best Paper Award.
PMID- 29949205
TI - Rural-Urban Difference in Workplace Supports and Impacts for Employed Caregivers.
AB - PURPOSE: This study examines rural-urban differences in employed caregivers'
access to workplace supports, negative impacts of caregiving on work, and the
association between work and caregiver strain, which can have negative impacts on
health. METHODS: We used a cross-sectional analysis of employed caregivers (n =
635) from the 2015 Caregiving in the US survey, including bivariate comparisons
of caregiver characteristics, access to workplace benefits, and workplace impacts
by rural-urban location, as well as ordered logistic regression models to assess
the relationship between workplace benefits and impacts and caregiver strain,
stratified by rural-urban location. FINDINGS: Employed rural caregivers had
significantly fewer workplace benefits available to them (1.3 out of 5 vs 1.9, P
< .001), compared with urban caregivers. In particular, employed rural caregivers
were less likely to have access to telecommuting, employee assistance programs,
and paid leave. For the full sample, having more negative workplace impacts was
associated with greater caregiver strain (adjusted odds ratio [AOR]: 1.65, P <
.001); for employed rural caregivers, using paid help for caregiving was
associated with more strain (AOR: 4.39, P < .05). CONCLUSIONS: More should be
done to support all employed caregivers, especially those in rural locations who
have more limited access to workplace supports and who may be more negatively
impacted by the financial toll of caregiving and of missing work because of
caregiving responsibilities. Interventions could range from employer-initiated
programs to local, state, or national policies to improve supports provided to
employed caregivers in urban and rural areas.
PMID- 29949207
TI - Corrigendum.
PMID- 29949208
TI - Epstein-Barr virus post-transplant lymphoproliferative disease (PTLD) after
hematopoietic stem cell transplantation.
AB - Epstein-Barr virus (EBV) viremia and post-transplant lymphoproliferative disease
(PTLD) are severe complications after hematopoietic stem cell transplantation
(HSCT). A series of risk factors have been found to predict EBV viremia and PTLD,
including the T-cell depletion, reduced intensity conditioning, and alternative
donor. The rituximab pre-emptive therapy could improve PTLD prognosis
significantly, but the trigger of initiating rituximab pre-emptive therapy has
not been well established. Additionally, EBV-specific cytotoxic T cell (CTL) is a
promising approach to treat EBV-PTLD.
PMID- 29949209
TI - Charge- and Size-Complementary Multimetal-Induced Morphology and Phase Control in
Zeolite-Type Metal Chalcogenides.
AB - Zeolite-type chalcogenides are desirable due to their integration between
porosity and semiconductivity. CPM-120, with super-sodalite topology (Zeolite
Structure Code: RWY), is among the few zeolite-type chalcogenides with permanent
porosity, and is the only chalcogenide with a zeolite code. Importantly, the RWY
type has evolved into a platform for studying properties of porous chalcogenides.
Yet so far, few studies have been made to probe the effects of synthetic
parameters and framework compositions on this platform. Here, we probe the
effects of the third metal type (Ga3+ , In3+ , Cd2+ , and Sn4+ ) on the Zn2+
/Ge4+ /S2- platform. We find that charge-complementary and size-compatible Ga3+
leads to the synthesis of CPM-120-ZnGaGeS which is the first trimetallic zeolite
type chalcogenide, with improved crystal morphology and reproducibility. We also
find that charge-compatible and size-complementary cations (Cd2+ or Sn4+ ) can
induce an abrupt phase transition from super-sodalite to super-diamond, also with
unprecedented trimetallic T2 clusters. For In3+ , which is dual-complementary
(charge and size), a gradual phase transition is observed with increasing In3+
amount. Furthermore, by controlling the cluster composition, tunable band gaps
can be realized. These materials show promising properties such as high CO2
uptake (4.32 mmol cm-3 , 298 K, 1 bar) and high photocatalytic activity.
PMID- 29949210
TI - Health champions in South London: evaluation of training, and impact on public
health.
AB - OBJECTIVES: The Healthy Living Pharmacy framework, introduced in England in 2008,
provides a tailored approach to the implementation of pharmacy services locally,
facilitated by qualified 'Health Champions' (HCs). The study aimed to evaluate
the perceived value of the 1-day level 2 HC training by assessing knowledge and
confidence of HC pre- and post-training, and changes in practice. The views of
additional stakeholders on factors that either obstructed or facilitated pharmacy
engagement are also explored. METHODS: This study used a mixed method approach.
Pre- and post-training surveys evaluating HC pre-existing knowledge and
understanding of their role were used. Additionally, qualitative semi-structured
interviews were undertaken with four key groups: participating pharmacists, non
participating pharmacists, Local Pharmaceutical Committee leads and Public Health
Leads from Public Health England. KEY FINDINGS: A total of 354 pre-training
evaluation surveys were completed on the training day (100%), compared to 54 post
evaluation postal surveys with a 19% (n = 54/282) response rate. The post
evaluation of the training indicated that 83% (n = 45) of qualified HC were
actively implementing their new role, with observed increased confidence and
service provision. From the 22 interviews conducted two major themes emerged
including: Training and Impact. Training had a positive impact on staff knowledge
and confidence plus service delivery. CONCLUSION: An immediate impact was
observed in increasing HC knowledge and confidence, service delivery and
awareness of facilities for patient sign-posting. There was no statistical
evidence to support a positive effect stemming from training on services.
However, it was identified that time and further training were needed to both
provide and assess value within local public health.
PMID- 29949212
TI - Multigenerational and transgenerational effects of paternal exposure to drugs of
abuse on behavioral and neural function.
AB - Addictions are highly heritable disorders, with heritability estimates ranging
from 39% to 72%. Multiple studies suggest a link between paternal drug abuse and
addiction in their children. However, patterns of inheritance cannot be explained
purely by Mendelian genetic mechanisms. Exposure to drugs of abuse results in
epigenetic changes that may be passed on through the germline. This mechanism of
epigenetic transgenerational inheritance may provide a link between paternal drug
exposure and addiction susceptibility in the offspring. Recent studies have begun
to investigate the effect of paternal drug exposure on behavioral and
neurobiological phenotypes in offspring of drug-exposed fathers in rodent models.
This review aims to discuss behavioral and neural effects of paternal exposure to
alcohol, cocaine, opioids, and nicotine. Although a special focus will be on
addiction-relevant behaviors, additional behavioral effects including cognition,
anxiety, and depressive-like behaviors will be discussed.
PMID- 29949211
TI - Quantitative and Orthogonal Formation and Reactivity of SuFEx Platforms.
AB - The constraints of minute reactant amounts and the impossibility to remove any
undesired surface-bound products during monolayer functionalization of a surface
necessitate the selection of efficient, modular and orthogonal reactions that
lead to quantitative conversions. Herein, we explore the character of sulfur
fluoride exchange (SuFEx) reactions on a surface, and explore the applicability
for quantitative and orthogonal surface functionalization. To this end, we
demonstrate the use of ethenesulfonyl fluoride (ESF) as an efficient SuFEx linker
for creating "SuFEx-able" monolayer surfaces, enabling three distinct approaches
to utilize SuFEx chemistry on a surface. The first approach relies on a di-SuFEx
loading allowing dual functionalization with a nucleophile, while the two latter
approaches focus on dual (CuAAC-SuFEx/SPOCQ-SuFEx) click platforms. The resultant
strategies allow facile attachment of two different substrates sequentially on
the same platform. Along the way we also demonstrate the Michael addition of
ethenesulfonyl fluoride to be a quantitative surface-bound reaction, indicating
significant promise in materials science for this reaction.
PMID- 29949213
TI - The therapeutic potential of kratom.
PMID- 29949214
TI - Ultrafine FeCu Alloy Nanoparticles Magnetically Immobilized in Amine-Rich Silica
Spheres for Dehalogenation-Proof Hydrogenation of Nitroarenes.
AB - A novel core-shell structured nanocatalyst (Fe3 O4 @SiO2 -NH2 -FeCu
nanoparticles) with ultrafine FeCu alloy NPs magnetically immobilized in porous
silica has been fabricated. The obtained catalyst revealed excellent activity and
chemoselectivity for catalyzing the hydrogenation of nitroarenes to corresponding
anilines using hydrazine hydrate as the hydrogen source, and the reaction could
be carried out smoothly in water, which is an environmentally friendly solvent.
The FeCu alloy effectively prevented the dehalogenation of halonitroarenes, and X
ray photoelectron spectroscopy (XPS) study showed that it resulted from the
electron-enrichment of Fe from Cu. A kinetics study indicated that the reaction
order was about 1.5 towards 4-CNB and the apparent active energy (Ea ) was 48.1
kJ mol-1 , which is a relatively low value. Furthermore, the FeCu NPs are
magnetically immobilized in the silica spheres (Fe3 O4 @SiO2 ), therefore the
catalyst can be easily recovered by use of an external magnet and also possesses
a long life time.
PMID- 29949215
TI - Unilateral Pupil Dilation From Epidural Spinal Stimulation.
PMID- 29949216
TI - A new impedance-based method to guide RF ablation: Still scratching the surface?
PMID- 29949217
TI - Absorption Spectroscopy and Photophysics of a ReI -dppz Probe for DNA-Mediated
Charge Transport.
AB - Optical properties of [Re(CO)3 (dppz)(py)]+ (dppz=dipyrido[3,2-a:2',3'
c]phenazine; py=pyridine) in acetonitrile, water and DNA have been investigated
based on DFT, time-dependent-DFT (TD-DFT)/ conductor-like screening model, with
and without explicit solvent molecules, and molecular dynamics. Whereas implicit
solvent model is not appropriate to model optical properties of dppz-substituted
metal complexes, adding explicit solvent molecules in interaction with dppz
stabilizes the metal-to-ligand-charge-transfer (MLCT) transitions. Classical
molecular dynamics simulations point to an important conformational flexibility,
as evidenced by the coexistence of two conformers A and B. When considering the
conformational sampling, the lowest band of the absorption spectrum is red
shifted and broadened up to 500 nm in agreement with the experimental spectra
supporting important dynamical effects. The absorption spectra of [Re(CO)3
(dppz)(py-R)]+/ GC-DNA and [Re(CO)3 (dppz)(py-R)]+ /AT-DNA (R=CH2 -CH2 -COO- )
intercalated in both major or minor grooves exhibit a lowest energy charge
separated (CS) band at about 600 nm and 500 nm, respectively, corresponding
mainly to excitations from guanine and adenine to dppz. These states may play a
central role into DNA-mediated charge transport processes. The over stabilization
of the lowest 3 ILdppz state of [Re(CO)3 (dppz)(py)]+ in water as compared to
acetonitrile could be responsible for the quenching of emission in water.
PMID- 29949219
TI - Developmental changes in automatic rule-learning mechanisms across early
childhood.
AB - Infants' ability to learn complex linguistic regularities from early on has been
revealed by electrophysiological studies indicating that 3-month-olds, but not
adults, can automatically detect non-adjacent dependencies between syllables.
While different ERP responses in adults and infants suggest that both linguistic
rule learning and its link to basic auditory processing undergo developmental
changes, systematic investigations of the developmental trajectories are scarce.
In the present study, we assessed 2- and 4-year-olds' ERP indicators of pitch
discrimination and linguistic rule learning in a syllable-based oddball design.
To test for the relation between auditory discrimination and rule learning, ERP
responses to pitch changes were used as predictor for potential linguistic rule
learning effects. Results revealed that 2-year-olds, but not 4-year-olds, showed
ERP markers of rule learning. Although, 2-year-olds' rule learning was not
dependent on differences in pitch perception, 4-year-old children demonstrated a
dependency, such that those children who showed more pronounced responses to
pitch changes still showed an effect of rule learning. These results narrow down
the developmental decline of the ability for automatic linguistic rule learning
to the age between 2 and 4 years, and, moreover, point towards a strong
modification of this change by auditory processes. At an age when the ability of
automatic linguistic rule learning phases out, rule learning can still be
observed in children with enhanced auditory responses. The observed
interrelations are plausible causes for age-of-acquisition effects and inter
individual differences in language learning.
PMID- 29949218
TI - Multi-isotope provenancing of archaeological skeletons including cremations in a
reference area of the European Alps.
AB - RATIONALE: Due to the spatial heterogeneity of stable isotope ratios of single
elements measured in attempts to georeference bioarchaeological finds, multi
isotope fingerprints are frequently employed under the assumption that similar
isotopic signatures are indicative of similar shared environments by the
individuals studied. The extraction of the spatial information from multi-isotope
datasets, however, is challenging. METHODS: Gaussian mixture clustering of six-
to seven-dimensional isotopic fingerprints measured in archaeological animal and
human bones was performed. Uncremated animal bones served for an isotopic mapping
of a specific reference area of eminent archaeological importance, namely the Inn
Eisack-Adige passage across the European Alps. The fingerprints consist of 87
Sr/86 Sr, 208 Pb/204 Pb, 207 Pb/204 Pb, 206 Pb/204 Pb, 208 Pb/207 Pb, and 206
Pb/207 Pb ratios, and delta18 Ophosphate values in uncremated bone apatite, while
the thermally unstable delta18 O values of human cremations from this region were
discarded. RESULTS: The bone finds were successfully decontaminated. Animal and
human isotope clusters not only reflect individual similarities in the multi
isotopic fingerprints, but also permit a spatial allocation of the finds. This
holds also for cremated finds where the delta18 Ophosphate value is no longer
informative. To our knowledge, for the first time Pb stable isotopes have been
systematically studied in cremated skeletal remains and proved significant in a
region that was sought after for its ore deposits in prehistory. CONCLUSIONS:
Gaussian mixture clustering is a promising method for the interpretation of multi
isotopic fingerprints aiming at detecting and quantifying migration and trade.
PMID- 29949220
TI - Evapotranspiration and water yield of a pine-broadleaf forest are not altered by
long-term atmospheric [CO2 ] enrichment under native or enhanced soil fertility.
AB - Changes in evapotranspiration (ET) from terrestrial ecosystems affect their water
yield (WY), with considerable ecological and economic consequences. Increases in
surface runoff observed over the past century have been attributed to increasing
atmospheric CO2 concentrations resulting in reduced ET by terrestrial ecosystems.
Here, we evaluate the water balance of a Pinus taeda (L.) forest with a broadleaf
component that was exposed to atmospheric [CO2 ] enrichment (ECO2 ; +200 ppm) for
over 17 years and fertilization for 6 years, monitored with hundreds of
environmental and sap flux sensors on a half-hourly basis. These measurements
were synthesized using a one-dimensional Richard's equation model to evaluate
treatment differences in transpiration (T), evaporation (E), ET, and WY. We found
that ECO2 did not create significant differences in stand T, ET, or WY under
either native or enhanced soil fertility, despite a 20% and 13% increase in leaf
area index, respectively. While T, ET, and WY responded to fertilization, this
response was weak (<3% of mean annual precipitation). Likewise, while E responded
to ECO2 in the first 7 years of the study, this effect was of negligible
magnitude (<1% mean annual precipitation). Given the global range of conifers
similar to P. taeda, our results imply that recent observations of increased
global streamflow cannot be attributed to decreases in ET across all ecosystems,
demonstrating a great need for model-data synthesis activities to incorporate our
current understanding of terrestrial vegetation in global water cycle models.
PMID- 29949221
TI - Preoperative assessment of frailty predicts age-related events after hepatic
resection: a prospective multicenter study.
AB - BACKGROUND: Age-related events, such as cardiopulmonary complications, delirium,
transfer to a rehabilitation facility, and dependency are a major problem after
hepatic resection in the elderly. This prospective multicenter study aimed to
preoperatively evaluate frailty in the elderly according to a phenotypic frail
index, named the "Kihon Checklist (KCL)," to predict "age-related events" after
hepatic resection. METHODS: Between May 2016 and September 2017, 217
independently living patients who consented among all patients aged >=65 years
who planned to undergo hepatic resection were included in the study. Preoperative
frailty was defined as a total KCL score >=8. We analyzed clinical
characteristics and outcomes, including age-related events (major respiratory and
cardiac complications, delirium medication needed, transfer to rehabilitation
facility, and dependency) between patients with and without frailty. RESULTS: Of
the 217 patients, 63 and 154 were classified into the frail and non-frail groups,
respectively. The incidences of age-related events (31.7% vs. 7.8%, P < 0.001)
were higher in the frail group. Multivariate analysis indicated that frailty (P <
0.001, hazard ratio 5.16) and resection of >=2 sectors (P = 0.014, hazard ratio
2.98) were independent risk factors for age-related events. CONCLUSIONS: Frailty
evaluated by KCL in the elderly can predict postoperative age-related events
after hepatic resection.
PMID- 29949222
TI - Epidermal growth factor receptor targeted methotrexate and small interfering RNA
co-delivery.
AB - BACKGROUND: Developing new drug delivery carriers addressing chemoresistance is
still full of challenges and opportunities. As the rapid development of small
interfering RNA (siRNA) provides promising therapeutic perspectives, nanocarriers
for drug and siRNA co-delivery present new alternatives for cancer therapy.
METHODS: A co-delivery nanosystem for methotrexate (MTX) or gamma-glutamylated
derivatives (gE2 -MTX and gE5 -MTX) and antitumoral EG5 siRNA has been developed
utilizing the sequence defined cationic lipo-oligomers 454, 1021 and 1027. Based
on a lipo-oligomer-MTX-siRNA core, an epidermal growth factor receptor (EGFR)
targeted delivery system was established via post modification with the GE11
targeting peptide. RESULTS: Almost 100% MTX derivative incorporation was achieved
in gE2 -MTX or gE5 -MTX siRNA/454 polyplexes, whereas the particle sizes (100-150
nm) and siRNA binding abilities were well maintained. Our co-delivery system
greatly increased the MTX sensitivity of MTX resistant KB cells. Enhanced
cellular internalization of GE11 siRNA/454 polyplexes incorporating either gE2
MTX or gE5 -MTX was observed and attributed to GE11-mediated targeting of EGFR
overexpressing KB cells. GE11 modified gE2 -MTX or gE5 -MTX EG5 siRNA polyplexes
illustrated the highest anti-tumoral activities compared to free MTX or
nontargeted polyplexes. The His-containing gE2 -MTX or gE5 -MTX siRNA/1027
polyplexes showed increased tumor cell killing compared to the His-free analogous
1021 polyplexes. CONCLUSIONS: A new strategy for co-delivering negatively charged
MTX and cytotoxic siRNA has been developed by utilizing sequence defined cationic
lipo-oligomers. Mediated by the combined effect of antifolate MTX, antimitotic
EG5 siRNA and EGFR targeting by GE11, superior tumor cell killing was obtained
with GE11 gE2 -MTX or gE5 -MTX EG5 siRNA/454 polyplexes.
PMID- 29949223
TI - Salivary fetuin-A, S100A12, and high-sensitivity C-reactive protein levels in
periodontal diseases.
AB - AIM: Hs-CRP, fetuin-A, and S100A12 are acute-phase proteins associated with many
systemic diseases and conditions. The aim of this study was to determine the
clinical parameters and salivary Hs-CRP, fetuin-A, and S100A12 levels before and
after nonsurgical periodontal treatments in the patients with periodontal
diseases. MATERIALS AND METHODS: A total of 54 subjects were divided into three
groups of 18 patients each: periodontally healthy, gingivitis, and chronic
periodontitis. Clinical periodontal parameters; salivary Hs-CRP, fetuin-A, and
S100A12 levels; and salivary flow rates were evaluated at baseline and a month
after the treatments. RESULTS: Fetuin-A and S100A12 were significantly lower and
Hs-CRP levels were significantly higher in the chronic periodontitis and
gingivitis groups than in the control group at baseline (p < 0.01). For the
gingivitis and chronic periodontitis groups, the posttreatment levels of salivary
fetuin-A and S100A12 were higher than the baseline levels of the same (p < 0.01).
There was a negative correlation between Hs-CRP and fetuin-A and Hs-CRP and
S100A12 (p < 0.001) and a positive correlation between fetuin-A and S100A12 (p <
0.05) at baseline. CONCLUSIONS: Salivary fetuin-A and S100A12 levels decreased
with increasing severity of periodontal disease. These results suggest that
salivary fetuin-A may play an important role as a negative acute-phase protein in
periodontal diseases.
PMID- 29949224
TI - Nickel-Iron Layered Double Hydroxide Hollow Polyhedrons as a Superior Sulfur Host
for Lithium-Sulfur Batteries.
AB - We have designed and synthesized novel hollow Ni/Fe layered double hydroxide
(LDH) polyhedrons as an advanced sulfur host for enhancing the performance of
lithium-sulfur (Li-S) batteries. The Ni/Fe LDH host shows multiple advantages.
First, the Ni/Fe LDH shells can provide sufficient sulfiphilic sites for
chemically bonding with polysulfides. Second, the hollow architecture can provide
sufficient inner space for both loading a large amount of sulfur and
accommodating its large volumetric expansion. Moreover, once the active material
is confined within the host, the shells could easily restrict the outward
diffusion of polysulfides, guaranteeing prolonged cycle life even with high
sulfur loading. As a result, the S@Ni/Fe LDH cathode has successfully solved the
main issues related to sulfur electrodes, and it exhibits significantly improved
electrochemical performances with prolonged life over 1000 cycles and excellent
rate properties.
PMID- 29949225
TI - A multicentre study of oral paracoccidioidomycosis: Analysis of 320 cases and
literature review.
AB - OBJECTIVES: To investigate the frequency of oral paracoccidioidomycosis from
representative geographical regions of Brazil and to compare the data with a
literature review. MATERIALS AND METHODS: A retrospective study was conducted on
108,304 biopsies obtained from 1953 to 2016 at six Brazilian oral and
maxillofacial pathology services. Demographic data and clinical and
histopathological diagnosis of oral paracoccidioidomycosis were evaluated. A
literature review of oral paracoccidioidomycosis studies published in three
electronic databases was carried out. Data were analysed descriptively. RESULTS:
A total of 320 cases of oral paracoccidioidomycosis were surveyed (0.3% of the
oral lesions at the centres studied). The lesions were more frequent among male
patients. The gingiva/alveolar ridge was the most affected site. Mean age of
affected individuals was 51.3 years (+/-11.7). The literature review showed a
higher incidence of oral paracoccidioidomycosis in the south-east and south
regions of Brazil. Male individuals and individuals between 50 and 59 years were
most affected. CONCLUSIONS: Oral paracoccidioidomycosis is an uncommon lesion
observed in oral biopsy samples. The differences in the relative frequency of
oral paracoccidioidomycosis are related to geographical variations. Men between
50 and 59 years are more affected. This study provides helpful information for
clinicians in the diagnosis of oral paracoccidioidomycosis.
PMID- 29949226
TI - Amelogenesis imperfecta: A novel FAM83H mutation and characteristics of
periodontal ligament cells.
AB - OBJECTIVE: To delineate orodental features, dental mineral density, genetic
aetiology and cellular characteristics associated with amelogenesis imperfecta
(AI). MATERIALS AND METHODS: Three affected patients in a family were recruited.
Whole-exome sequencing was used to identify mutations confirmed by Sanger
sequencing. The proband's teeth were subjected for mineral density analysis by
microcomputerised tomography and characterisation of periodontal ligament cells
(PDLCs). RESULTS: The patients presented yellow-brown, pitted and irregular
enamel. A novel nonsense mutation, c.1261G>T, p.E421*, in exon 5 of the FAM83H
was identified. The mineral density of the enamel was significantly decreased in
the proband. The patient's PDLCs (FAM83H cells) exhibited reduced ability of cell
proliferation and colony-forming unit compared with controls. The formation of
stress fibres was remarkably present. Upon cultured in osteogenic induction
medium, FAM83H cells, at day 7 compared to day 3, had a significant reduction of
BSP, COL1 and OCN mRNA expression and no significant change in RUNX2. The
upregulation of ALP mRNA levels and mineral deposition were comparable between
FAM83H and control cells. CONCLUSIONS: We identified the novel mutation in FAM83H
associated with autosomal dominant hypocalcified AI. The FAM83H cells showed
reduced cell proliferation and expression of osteogenic markers, suggesting
altered PDLCs in FAM83H-associated AI.
PMID- 29949227
TI - Early discharge in acute mental health: A rapid literature review.
AB - Long psychiatric hospital stays are unpopular with services users, harmful, and
costly. Economic pressures alongside a drive for recovery-orientated care in the
least restrictive contexts have led to increasing pressure to discharge people
from hospital early. Hospital discharge is, however, complex, stressful, and
risky for service users and families. This rapid literature review aimed to
assess what is known about early discharge in acute mental health. Searches were
conducted in nine bibliographic databases, reference lists, and targeted grey
literature sources. Fourteen included papers focused on early discharge in mental
health, a population over 18 years with a mental health condition, and reported
outcomes on therapeutic care or service delivery. Quality appraisal was
undertaken using The Mixed Method Appraisal Tool. The meta-summary of the
literature found that early discharge was neither provided to all inpatients nor
limited to the Crisis Resolution and Home Treatment (CRHT) service model
internationally. Early discharge interventions required collaborative working and
discharge planning. It was not associated with unplanned readmissions and had a
small effect on length of stay. Most studies reported service outcomes, whereas
health outcomes were underreported. Professionals and service users were positive
about early discharge and service users asked for peer support. Carers preferred
hospital or day hospital care suggesting their need for respite. Limitations in
the scope, detail, and quality of the evidence about early discharge leave an
unclear picture of the components of early discharge as an intervention, its
effectiveness, cost-effectiveness, or outcomes.
PMID- 29949228
TI - Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom)
alkaloids mitragynine and 7-hydroxymitragynine.
AB - Kratom, derived from the plant Mitragyna speciosa, is receiving increased
attention as an alternative to traditional opiates and as a replacement therapy
for opiate dependence. Mitragynine (MG) and 7-hydroxymitragynine (7-HMG) are
major psychoactive constituents of kratom. While MG and 7-HMG share behavioral
and analgesic properties with morphine, their reinforcing effects have not been
examined to date. 7-HMG, but not MG, substituted for morphine self-administration
in a dose-dependent manner in the rat self-administration paradigm. Following the
substitution procedure, re-assessment of morphine self-administration revealed a
significant increase following 7-HMG and a significant decrease following MG
substitution. In a separate cohort, 7-HMG, but not MG, engendered and maintained
intravenous self-administration in a dose-dependent manner. The effects of
pretreatment with nalxonaxine (NLXZ), a MU1 opiate receptor antagonist, and
naltrindole (NTI), a delta opiate receptor antagonist, on 7-HMG and morphine self
administration were also examined. Both NLXZ and NTI reduced 7-HMG self
administration, whereas only NLXZ decreased morphine intake. The present results
are the first to demonstrate that 7-HMG is readily self-administered, and the
reinforcing effects of 7-HMG are mediated in part by MU and delta opiate
receptors. In addition, prior exposure to 7-HMG increased subsequent morphine
intake whereas prior exposure to MG decreased morphine intake. The present
findings indicate that MG does not have abuse potential and reduces morphine
intake, desired characteristics of candidate pharmacotherapies for opiate
addiction and withdrawal, whereas 7-HMG should be considered a kratom constituent
with high abuse potential that may also increase the intake of other opiates.
PMID- 29949229
TI - The auxin receptor TIR1 homolog (PagFBL1) regulates adventitious rooting through
interactions with Aux/IAA28 in Populus.
AB - Adventitious roots occur naturally in many species and can also be induced from
explants of some tree species including Populus, providing an important means of
clonal propagation. Auxin has been identified as playing a crucial role in
adventitious root formation, but the associated molecular regulatory mechanisms
need to be elucidated. In this study, we examined the role of PagFBL1, the hybrid
poplar (Populus alba * P. glandulosa clone 84K) homolog of Arabidopsis auxin
receptor TIR1, in adventitious root formation in poplar. Similar to the
distribution pattern of auxin during initiation of adventitious roots, PagFBL1
expression was concentrated in the cambium and secondary phloem in stems during
adventitious root induction and initiation phases, but decreased in emerging
adventitious root primordia. Overexpressing PagFBL1 stimulated adventitious root
formation and increased root biomass, while knock-down of PagFBL1 transcript
levels delayed adventitious root formation and decreased root biomass.
Transcriptome analyses of PagFBL1 overexpressing lines indicated that an
extensive remodelling of gene expression was stimulated by auxin signalling
pathway during early adventitious root formation. In addition, PagIAA28 was
identified as downstream targets of PagFBL1. We propose that the PagFBL1-PagIAA28
module promotes adventitious rooting and could be targeted to improve Populus
propagation by cuttings.
PMID- 29949230
TI - Low-Coordinated Titanium(III) Alkyl-Molecular and Surface-Complexes: Detailed
Structure from Advanced EPR Spectroscopy.
AB - The structure of paramagnetic surface species is notoriously difficult to
determine. For TiIII centers related to Ziegler-Natta catalysis, we demonstrate
here that detailed structural information can be obtained by advanced EPR
spectroscopy and DFT computations, benchmarked on molecular analogs. The
hyperfine sublevel correlation (HYSCORE) spectra obtained after reaction with 13
C-labeled ethylene provides information about the coupling with a proton in the
first coordination sphere of TiIII as well as significant 13 C hyperfine coupling
and thereby allows structural assignment of the surface species.
PMID- 29949231
TI - Predictors and enablers of mental health nurses' family-focused practice.
AB - Family-focused practice improves outcomes for families where parents have a
mental illness. However, there is limited understanding regarding the factors
that predict and enable these practices. This study aimed to identify factors
that predict and enable mental health nurses' family-focused practice. A
sequential mixed methods design was used. A total of 343 mental health nurses,
practicing in 12 mental health services (in acute inpatient and community
settings), throughout Ireland completed the Family Focused Mental Health Practice
Questionnaire, measuring family-focused behaviours and other factors that impact
family-focused activities. Hierarchical multiple regression identified 14
predictors of family-focused practice. The most important predictors noted were
nurses' skill and knowledge, own parenting experience, and work setting (i.e.
community). Fourteen nurses, who achieved high scores on the questionnaire,
subsequently participated in semistructured interviews to elaborate on enablers
of family-focused practice. Participants described drawing on their parenting
experiences to normalize parenting challenges, encouraging service users to
disclose parenting concerns, and promoting trust. The opportunity to visit a
service user's home allowed them to observe how the parent was coping and forge a
close relationship with them. Nurses' personal characteristics and work setting
are key factors in determining family-focused practice. This study extends
current research by clearly highlighting predictors of family-focused practice
and reporting how various enablers promoted family-focused practice. The capacity
of nurses to support families has training, organizational and policy
implications within adult mental health services in Ireland and elsewhere.
PMID- 29949232
TI - The effects of melatonin supplementation on mental health, metabolic and genetic
profiles in patients under methadone maintenance treatment.
AB - This investigation was designed to determine the effect of melatonin
supplementation on mental health parameters, metabolic and genetic profiles in
patients under methadone maintenance treatment (MMT). This randomized, double
blind, placebo-controlled, clinical trial was conducted among 54 patients under
MMT. Participants were randomly allocated to receive either 10 mg melatonin (2
melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour
before bedtime for 12 weeks. Melatonin supplementation significantly decreased
Pittsburgh Sleep Quality Index (beta -4.08; 95 percent CI, -5.51, -2.65; P <
0.001), Beck Depression Inventory index (beta -5.46; 95% CI, -8.92, -2.00; P =
0.003) and Beck Anxiety Inventory index (beta -3.87; 95% CI, -5.96, -1.77; P =
0.001) and significantly increased International Index of Erectile Functions
(beta 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects
who received melatonin supplements had significantly lower serum insulin levels
(beta -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment
insulin resistance (beta -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher
quantitative insulin sensitivity check index (beta 0.01; 95% CI, 0.004, 0.02; P =
0.009) and HDL-cholesterol levels (beta 3.71; 95% CI, 1.77, 5.64; P = 0.002)
compared to placebo. Additionally, melatonin intake resulted in a significant
reduction in serum high sensitivity C-reactive protein (beta -0.15; 95% CI,
0.27, -0.02; P = 0.02), malondialdehyde (beta -0.31; 95% CI, -0.57, -0.05; P =
0.02) and protein carbonyl (beta -0.06; 95% CI, -0.09, -0.04; P < 0.001). This
trial indicated that taking melatonin supplements for 12 weeks by patients under
MMT had beneficial effects on their mental health metabolic profiles.
PMID- 29949233
TI - Oral and dental health care during pregnancy: Evaluating a theory-driven
intervention.
AB - OBJECTIVE: The present research aimed to investigate the effect of an educational
intervention based on the health belief model in pregnant women visiting the
healthcare centers in the west of Tehran in 2016. MATERIALS AND METHODS: The
present experimental research was conducted on 135 pregnant women visiting the
healthcare centers in the west of Tehran. The subjects were selected through a
randomized multistratified sampling and were divided into an experimental and a
control group. The collected data were then statistically analyzed in SPSS
ver.16. To do so, descriptive statistics and inferential statistics were used
including the independent-samples t-test, repeated-measures one-way ANOVA and
paired-sample t-test. RESULTS: The present findings revealed a statistically
significant difference between the experimental and control groups in terms of
immediate post-test results including perceived sensitivity, severity, benefits,
barriers, and self-efficacy along with awareness and performance constructs (p ?
0.001). Moreover, two months after the intervention, except for the perceived
sensitivity construct (p = 0.088), the two groups diverged significantly in terms
of the other constructs (p ? 0.001). CONCLUSIONS: The educational intervention
driven by the health belief theory showed to be effective on pregnant women and
can help to promote preventive behaviors of tooth decay.
PMID- 29949234
TI - Classifying and characterizing nicotine use disorder with high accuracy using
machine learning and resting-state fMRI.
AB - Cigarette smoking continues to be a leading cause of preventable morbidity and
mortality. Although the majority of smokers report making a quit attempt in the
past year, smoking cessation rates remain modest. Thus, developing accurate, data
driven methods that can classify and characterize the neural features of nicotine
use disorder (NUD) would be a powerful clinical tool that could aid in optimizing
treatment development and guide treatment modifications. This investigation
applied support vector machine-based classification to resting-state functional
connectivity (rsFC) data from individuals diagnosed with NUD (n = 108; 63 male)
and matched nonsmoking controls (n = 108; 63 male) and multi-dimensional scaling
to visualize the heterogeneity of NUD in individual smokers based on rsFC
measures. Machine-based learning models identified five resting-state networks
that played a role in distinguishing smokers from controls: the posterior and
anterior default mode networks, the sensorimotor network, the salience network
and the right executive control network. The classification method constructed
classifiers with an average correct classification rate of 88.1 percent and an
average area under the curve of 0.93. Compared with controls, individuals with
NUD had weaker functional connectivity measures within these networks (P < 0.05,
false discovery rate corrected). Further, multi-dimensional scaling visualization
demonstrated that controls were similar to each other whereas individuals with
NUD had less similarity to controls and to other individuals with NUD. Our
findings build upon previous literature demonstrating that machine learning-based
approaches to classifying rsFC data offer a valuable technique to understanding
network-level differences in nicotine-related neurobiology and extend previous
findings by improving classification accuracy and demonstrating the heterogeneity
in resting-state networks of individuals with NUD.
PMID- 29949236
TI - Carbene in Cupredoxin Protein Scaffolds: Replacement of a Histidine Ligand in the
Active Site Substantially Alters Copper Redox Properties.
AB - N-heterocyclic carbene (NHC) ligands have had a major impact in homogeneous
catalysis, however, their potential role in biological systems is essentially
unexplored. We replaced a copper-coordinating histidine (His) in the active site
of the redox enzyme azurin with exogenous dimethyl imidazolylidene. This NHC
rapidly restores the type-1 Cu center, with spectroscopic properties (EPR,
UV/Vis) that are identical to those from N-coordination of the His in the wild
type. However, the introduction of the NHC markedly alters the redox potential of
the metal, which is a key functionality of this blue copper protein. These
results suggest that C-bonding for histidine is plausible and a potentially
relevant bonding mode of redox-active metalloenzymes in their (transient) active
states.
PMID- 29949235
TI - MicroRNAs as potential biomarkers for the diagnosis of glioma: A systematic
review and meta-analysis.
AB - Glioma is the most common central nervous system tumor and associated with poor
prognosis. Identifying effective diagnostic biomarkers for glioma is particularly
important in order to guide optimizing treatment. MicroRNAs (miRNAs) have drawn
much attention because of their diagnostic value in diverse cancers, including
glioma. We summarized studies to identify the potential diagnostic values of
miRNAs in glioma patients. We included articles reporting miRNAs for
differentiation of glioma patients from controls. We calculated sensitivities,
specificities, and area under the curves (AUC) of individual miRNA and miRNA
panels. We found that overall sensitivity, specificity, and AUC of miRNAs in
diagnosis of glioma were 85% (95% confidence interval [CI]: 0.81-0.89), 90% (95%
CI 0.85-0.93), and 93% (95% CI 0.91-0.95), respectively. Meta-regression analysis
showed that the detection of miRNAs expression in cerebrospinal fluid (CSF) and
brain tissue largely improved the diagnostic accuracy. Likewise, panels of
multiple miRNAs could enhance the pooled sensitivity. Moreover, AUC of miR-21 was
0.88, with 86% sensitivity and 94% specificity. This study demonstrated that
miRNAs could function as potential diagnosis markers in glioma. Detection of
miRNAs in CSF and brain tissue displays high accuracy in the diagnosis of glioma.
PMID- 29949237
TI - Loren Parsons' contribution to addiction neurobiology.
AB - Loren (Larry) H. Parsons passed away at the age of 51. In spite of his premature
departure, Larry much contributed to the drug abuse field. Since his graduate
studies for the Ph.D. in Chemistry in J.B. Justice lab, microdialysis is the
tread that links Larry's research topics, namely, the role of dopamine (DA),
serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate and endocannabinoids
(eCBs) in drug reinforcement and dependence. Larry was the first to show that
abstinence from chronic cocaine reduces extracellular DA in the NAc, consistent
with the so called 'dopamine depletion hypothesis' of cocaine addiction. Another
Larry's major contributions are the studies on 5-HT and 5-HT receptors' role in
cocaine stimulant actions, which resulted in the identification of 5-HT1B
receptors as a critical substrate of cocaine reinforcement. By applying mass
spectrometry to eCBs analysis in brain dialysates, Larry's lab showed that
ethanol, heroin, nicotine and cocaine differentially affect anandamide and 2
arachidonoylglicerol overflow in the NAc shell, a critical site of drugs of abuse
DA stimulant actions. Larry also applied microdialysis to study GABA and
glutamate's role in ethanol dependence and heroin reinforcement, providing in
vivo evidence for a sensitization of corticotropin-releasing factor-dependent
release of GABA in the central amygdala in withdrawal from chronic ethanol and
for a reduction of GABA transmission in the ventral pallidum in heroin but not
cocaine intravenous self-administration. Larry showed the wide possibilities of
microdialysis as a general purpose methodology for monitoring neurotransmitters
and neuromodulators in the brain extracellular compartment. From this viewpoint,
he stands as the best advocate for microdialysis.
PMID- 29949239
TI - A route to understanding yeast cellular envelope - plasma membrane lipids
interplaying in cell wall integrity.
AB - Sphingolipids and sterols are major components of the plasma membrane in
eukaryotic cells. A recent study provides new insight into the intricate but
fundamental relationship between Saccharomyces cerevisiae membrane lipid
composition and membrane biophysical properties, by showing that sphingolipids
and sterols co-ordinately regulate cell wall integrity.
PMID- 29949238
TI - C1q/TNF-related peptide 8 (CTRP8) promotes temozolomide resistance in human
glioblastoma.
AB - The C1q/TNF-related peptide 8 (CTRP8) has recently emerged as a novel ligand of
the G protein-coupled receptor RXFP1 in the fatal brain tumor glioblastoma (GBM).
We previously demonstrated that the CTRP8-RXFP1 ligand-receptor system promotes
motility and matrix invasion of patient GBM and U87 MG cells by specific
phosphorylation of PI3 kinase and protein kinase C. Here, we demonstrate a novel
role for CTRP8 in protecting human GBM cells against the DNA alkylating damage of
temozolomide (TMZ), the standard chemotherapy drug used to treat GBM. This DNA
protective role of CTRP8 required a functional RXFP1-STAT3 signaling cascade in
GBM cells. We identified N-methylpurine DNA glycosylase (MPG), a monofunctional
glycosylase that initiates base excision repair pathway by generating an
apurinic/apyrimidinic (AP) site, as a new CTRP8-RXFP1-STAT3 target in GBM. Upon
TMZ exposure, treatment with CTRP8 reduced the formation of AP sites and double
strand DNA breaks in GBM cells. This CTRP8 effect was independent of cellular
MGMT levels and was associated with decreased caspase 3/7 activity and increased
survival of human GBM. CTRP8-induced RXFP1 activation caused an increase in
cellular protein levels of the anti-apoptotic Bcl members and STAT3 targets Bcl-2
and Bcl-XL in human GBM. Collectively, our results demonstrate a novel
multipronged and clinically relevant mechanism by which the CTRP8-RXFP1 ligand
receptor system exerts a DNA protective function against TMZ chemotherapeutic
stress in GBM. This CTRP8-RXFP1-STAT3 axis is a novel determinant of TMZ
responsiveness/chemoresistance and an emerging new drug target for improved
treatment of human GBM.
PMID- 29949240
TI - The mechanistic basis for chromatin regulation by pioneer transcription factors.
AB - Pioneer transcription factors play a primary role in establishing competence for
gene expression and initiating cellular programming and reprogramming, and their
dysregulation causes severe effects on human health, such as promoting
tumorigenesis. Although more than 200 transcription factors are expressed in each
cell type, only a small number of transcription factors are necessary to elicit
dramatic cell-fate changes in embryonic development and cell-fate conversion.
Among these key transcription factors, a subset called "pioneer transcription
factors" have a remarkable ability to target nucleosomal DNA, or closed
chromatin, early in development, often leading to the local opening of chromatin,
thereby establishing competence for gene expression. Although more key
transcription factors have been identified as pioneer transcription factors, the
molecular mechanisms behind their special properties are only beginning to be
revealed. Understanding the pioneering mechanisms will enhance our ability to
precisely control cell fate at will for research and therapeutic purposes. This
article is categorized under: Biological Mechanisms > Cell Fates Biological
Mechanisms > Regulatory Biology Developmental Biology > Lineages.
PMID- 29949241
TI - The spectrum of intraoral bacteria seen in patients with cleft palates in an
African setting.
AB - Dehiscence or palatal fistula formation following palatoplasty is a complication
that has grave consequences for the patient that include tissue loss, emotional
distress to the parents and patient, and further medical costs. Palatal
dehiscence or fistula formation is multifactorial following surgery-tension of
wound closure, poor patient adherence to postoperative orders and wound infection
are the most common causes for this. Oral colonization with pathogenic organisms
could play a role in wound healing complications. Identification of intraoral
bacteria among patients with cleft palates has thus far not been performed. To
identify the spectrum of intraoral bacteria in cleft palate patients in an
African setting; a retrospective, chart review was performed at Inkosi Albert
Luthuli Central Hospital-a quaternary hospital in Durban, South Africa. All
patients with unrepaired cleft palates who underwent palatoplasty in 2015 were
included. Fifty-two patients were included. Preoperative throat/palatal swabs
were taken prior to palatoplasty. The various bacteria cultured from the
aforementioned swabs were cataloged. Various bacteria were cultured. In total, 23
patients (44.2%) had positive swab cultures. Eighteen cultures (34.6%) had gram
positive growth only, four cultures (7.7%) had gram-negative growth only, while
one patient (1.9%) cultured both a gram-positive and a gram-negative organism.
Streptococcus viridans was the most commonly cultured organism (19.2%) while beta
hemolytic streptococci were cultured from only 4 swabs (7.7%). Our study
cataloged the commonly occurring bacteria found in unrepaired cleft palate
patients in Africa. Further research into the clinical significance of each
bacteria is advised.
PMID- 29949242
TI - Elongation factor P controls translation of the mgtA gene encoding a Mg2+
transporter during Salmonella infection.
AB - Ribosome often stalls on mRNA sequences harboring consecutive proline codons.
Elongation factor P (EF-P) is required for the stalled ribosome to continue
translation and thus the absence of EF-P affects translation of the associated
open reading frame. Here we report that EF-P controls translation of the mgtA
gene encoding a Mg2+ -transporting ATPase from the intracellualr pathogen
Salmonella enterica serovar Typhimurium. EF-P's effect on mgtA translation is
dependent on the 550th and 551st proline codons in the coding region and thus
substitution of those proline codons eliminates EF-P-mediated control of MgtA
protein without affecting the Mg2+ -transporting activity of the mgtA gene. The
Pro550 and Pro551-substituted mgtA gene promotes Salmonella's intramacrophage
survival and mouse virulence, suggesting that EF-P-mediated translational control
of the mgtA gene is required for Salmonella pathogenesis.
PMID- 29949243
TI - How can transcranial magnetic stimulation be used to causally manipulate memory
representations in the human brain?
AB - We present a focused review on the utility of transcranial magnetic stimulation
(TMS) for modulating memory, with a particular focus on multimodal approaches in
which TMS is paired with neuroimaging methods (electroencephalography and
magnetic resonance imaging (MRI)) to manipulate and measure working memory
processes. We contrast the utility of TMS for manipulating memory with other
forms of noninvasive brain stimulation, as well as different forms of TMS
including single-pulse, paired-pulse and repetitive TMS protocols. We discuss the
potential for TMS to address fundamental cognitive neuroscience questions about
the nature of memory processes and representations, while acknowledging the
considerable variability of behavioral and neural outcomes in TMS studies. Also
discussed are the limitations of this technology, current advancements that have
helped to defray the impact of these limitations, and suggestions for future
directions in research and methodology. This article is categorized under:
Neuroscience > Clinical Neuroscience Neuroscience > Cognition Psychology >
Memory.
PMID- 29949245
TI - Standard abbreviations.
PMID- 29949244
TI - Immunopeptidomics Special Issue.
PMID- 29949246
TI - Adherence to Follow-Up in First-Episode Psychosis: Ethnicity Factors and Case
Manager Perceptions.
AB - Objective: To determine whether visible minority patients with first-episode
psychosis are at higher risk for treatment nonadherence than white patients and
elicit the perceptions of case managers regarding visible minority patients.
Methods: Data for 168 patients referred to a tertiary first-episode psychosis
clinic from January 2008 to January 2012 were collected via chart review. For 110
patients, a questionnaire filled out by each patient's case manager collected
quantitative and qualitative data regarding the case managers' perceptions of
patients' insight, cooperation, and adherence to appointments and medication.
Differential treatment adherence in white and visible minority patients was
tested via chi2 analyses. Case manager ratings of adherence were compared to
objective data via Cohen kappa. Qualitative data were analyzed via thematic
analysis. Results: Black patients had poorer follow-up compared to other patients
(adjusted chi21 = 4.3, P = .04). Concordance of case manager-reported adherence
and chart data was significant for the visible minority group only (kappa = 0.4,
P = .002). In case manager perceptions, there was no significant difference
between ethnic groups in adherence to appointments and medication, insight, or
family involvement. Conclusions: Although Canada is often perceived as tolerant
of diversity, our data regarding poor follow-up in black patients indicate
similar problems to those reported in the United Kingdom and United States.
Clinicians may have low expectations for visible minority patients and thus
notice more consistently when these patients adhere to treatment. This is the
first study to examine ethnic differences in adherence to first-episode psychosis
follow-up in a Canadian setting.
PMID- 29949247
TI - The TRUTH about childhood poverty.
PMID- 29949248
TI - Standing up and SPEAKING OUT.
PMID- 29949249
TI - HOME ALONE?.
PMID- 29949250
TI - NHS NO MORE?.
PMID- 29949251
TI - Beat the STREET.
PMID- 29949252
TI - LET NOTHING YOU DISMAY.
PMID- 29949253
TI - The last 12 MONTHS.
PMID- 29949254
TI - Supporting pre-registration nurses within health visiting and school nursing.
AB - During the Health Visitor Implementation Plan (DH, 2011), health visiting teams
were flooded with high numbers of health visitor students and, as a result,
preregistration student nurse placements for both health visitor and school nurse
placements were reduced or temporarily suspended until its conclusion in 2015.
Since then, pre-registration placements within health visiting and school nursing
have been reactivated, and pre-registration students are once again able to join
the clinical learning environment of specialist community public health nursing
(SCPHN). The reintroduction of student nurses to some clinical areas and
firsttime introduction in others has generated questions from health visitors and
school nurses about pre-registration nurses and their learning needs. This
article aims to answer some of the queries we have encountered about developing
the quality of the practice learning environment, so that student nurses'
development is supported in accordance with the NMC Standards for pre
registration nursing education (NMC, 2010). This article may provide the
opportunity for professional development, reflection and learning that can
contribute towards revalidation.
PMID- 29949255
TI - Adverse effects of orthodontic treatments.
AB - Orthodontic therapy, like any other medical intervention, in addition to its
benefits carries the risk of potential complications and is associated with
adverse effects-including periodontal problems, external root resorptions, pulpal
changes, enamel damages (demineralization, discoloration, attrition),
temporomandibular disorders, infective endocarditis, soft tissue damages,
discomfort, pain and the risk of either aspiration or indigestion of medical
instruments and appliances. Usually these effects are multifactorial in origin-
most often a result of interactions between the patient, the dental practitioner
and the technical aspects of the appliances or techniques. With preventive
measurements and care, most of these complications can be either limited or
completely avoided. Therefore, every dental practitioner must be fully aware of
these effects and associated risk factors in order to maximize the treatment
outcome. The present review aims to summarize these effects of orthodontic
therapies, and provide a detailed description of factors and preventive measures,
in order to minimize these damages.
PMID- 29949256
TI - Smoking and Psoriasis as Synergistic Risk Factors in Periodontal disease.
AB - In the literature both smoking and psoriasis are discussed as predisposing
factors for chronic periodontal disease. It is also known that smoking leads to
deterioration in both psoriasis and periodontal disease. However, up to now, the
only study to address the question what effect the co-occurrence of psoriasis and
smoking has on the periodontal status of the individual, was a previous study of
ours. In the present study, we repeated our measurements in an extended sample.
82 psoriatic patients and 117 controls participated, who all received a full
mouth examination so that their periodontal status could be determined. The
analysis was aimed at finding out about to what extent the individual risk
factors (i.e. smoking and psoriasis) increased the chance of the occurrence of
the advanced stages of periodontal disease. The odds ratio for smoking was 1,32
(p = 0,465), and 1,85 for psoriasis (p = 0,163). In those patients who smoked,
the odds ratio was 6,22 (p < 0,001), which is three times higher than the simple
combination of odds. This suggests that the risk factors are in a synergistic
relationship.
PMID- 29949257
TI - The comprehensive periodontal, resorative end prosthodontic therapy of chronic
periodontitis Case presentation.
AB - Chronic periodontitis predictable responds to mechanical cleaning and cause
related periodontal surgery. Nowadays the therapeutic protocol of the chronic
periodontitis is widely known and scientifically proven. The therapy can be split
into two major phases, the inicial or cause related therapy and the surgical
therapy, however in the most of the cases the patients need complex periodontal,
restorative and prosthodontic therapy. The presented case demonstrates the
process and results of the complex treatment of a 55 years old patient suffering
from chronic periodontitis. The patient didn't have hopeless teeth. In the first
phase of the cause related periodontal therapy professional oral hygiene
treatment, scaling rootplaning and subgingival curettage were performed by
quadrants. At the re-evaluation after the conservative periodontal therapy there
was a significant pocket reduction in the mandibular quadrants, however there was
a need for surgical pocket therapy in the molar regions of the maxillary
quadrants. Modified Widman-flap surgery and osteoplasty were performed in both of
the maxillary quadrants. After the surgical periodontal therapy the revision of
the old root canal fillings was accomplished in the teeth 24, 36 and 47. Due to
an inflammatory root resorption, root resection was performed following the root
canal filling on the tooth 24. Three months after the root resection surgery, the
tooth was reinforced by a glass fiber post. Nine months postoperatively the
periapical area of the tooth 24 showed growing radioopacity After the second
reevaluation of patient's compliance and the healing tendencies full mouth
prosthodontic reheabilitation was provided. Metalloceramic crowns with a
supragingival margin were made on the teeth 12, 24 and 36, metalloceramic bridge
was made on the teeth 44 and 47. After the periodontal, restorative and
prosthodontic therapy were finished the patient was remanded every 3 months for
periodontal supportive therapy and could maintain excellent oral hygiene with a
plaque score under 20% and a bleeding score of 6%.
PMID- 29949258
TI - Changes of trends in the size of the dental implants in recent years Part 1. The
role of short implants in dental implantology The literature review.
AB - The requirements for osseointegration have been determined decades ago, among
which was the appropriate size of the dental implants. In the last few years, in
both - domestic and foreign literature- we can find more and more articles
suggesting short and narrow dental implants as a treatment possibility. They may
serve as an alternative to various bone grafting techniques and may replace the
time demanding, more invasive and expensive horizontal and vertical bone
augmentation procedures. Using short and narrow implants we can avoid
interventions often accompanied by serious complications, such as bone
distraction and inferior alveolar nerve transposition which pose greater risk for
the patient. Our objective is a two-part review of the periodic literature in
order to establish whether short and narrow dental implants can serve as a real
alternative treatment modality.
PMID- 29949260
TI - Standing up and speaking out.
PMID- 29949259
TI - Confident dads and better behaved children.
PMID- 29949261
TI - Identifying the vulnerable.
PMID- 29949262
TI - Time to recharge?.
PMID- 29949263
TI - Witnessing a widening divide.
PMID- 29949264
TI - A closer look.
PMID- 29949266
TI - Into the fold.
PMID- 29949265
TI - Alcohol: A high price to pay.
PMID- 29949267
TI - Loud & clear.
PMID- 29949268
TI - Horner's syndrome and epidural anesthesia in labor and cesarean section.
AB - Homer's syndrome (HS) is based on dysfunction of symphathetic nervous system at
the cervical canal. The signs of the syndrome occur on the same side as the
lesion of the sympathetic trunk and include: a constricted pupil, a weak-droopy
eyelid, apparent decreased sweating, and with or without inset eyeball. HS has
been observed as a rare complication of epidural anaesthesia in obstetrics during
labour or cesarean section. In parturients, it warrants further investigation as
other serious causes must be excluded, such as pancoast tumours, thoracic aortic
aneurysms, carotid dissection, neuroblastoma, and brainstem vascular
malformation. Management involves early diagnosis of the underlying benign
condition while treatment is based on appropriate conservative observation, as
most often the syndrome resolves spontaneously. However in very rare cases
immediate medical or surgical management is needed.
PMID- 29949269
TI - A second case of successful conception in a natural cycle despite a maximum
endometrial thickness in the follicular phase of four mm.
AB - PURPOSE: To report the second case of successful conception in a natural cycle
despite a maximum endometrial thickness in the late follicular phase of four mm.
MATERIALS AND METHODS: A 31-year-old woman with short term infertility was
evaluated for follicular endometrial maturation with pelvic sonography. RESULTS:
She was treated with progesterone in the luteal phase. Despite attaining a very
good serum estradiol and having a longer follicular phase (with then more time of
estrogen exposure to increase the endometrial thickness) she conceived in this
cycle of investigation. CONCLUSIONS: Reporting a successful second case makes it
less likely that the first case was a miracle. The odds are that there have been
other pregnancies with four-mm endometrial thickness in natural cycles,without
follicle maturing drugs that have either not been reported, or more likely, not
evaluated.
PMID- 29949270
TI - Laparoscopic abdominal cerclage after radical vaginal trachelectomy.
AB - BACKGROUND: The incidence of cervical cancer (CC) in Slovenia in 2011 was 13.2
per 100,000 women. The treatment of early stages of invasive cervical carcinoma
involves several surgical techniques. In this article the authors would like to
present a new combination of two methods which help to preserve fertility and to
improve pregnancy outcome. The first procedure, radical vaginal trachelectomy
(RVT), begins with laparoscopic pelvic lymphadenectomy. All suspicious lymph
nodes are sent to frozen section. If those lymph nodes are negative, the
procedure continues vaginally. Almost the entire cervix is removed with
parametria and vaginal cuff. Permanent cerclage stitch is applied and covered
with vagina on what is left of uterus. Second procedure, laparoscopic abdominal
cerclage (LAC), begins with pneumoperitoneum. Mersilene tape is introduced in the
abdominal cavity and placed through the visceral peritoneum at the isthmic part
of the uterus with a Berci's needle. It is knotted and remains permanently.
MATERIALS AND METHODS: For the first procedure all the patients with confirmed
cervical carcinoma (FIGO Stage IA1, IA2, and IB1) and with the desire for
fertility were recruited. For the second procedure, all the patients after RVT
and after miscarriage after 14th week of gestation were recruited. RESULTS: RVT
was performed in 15 patients and laparoscopic abdominal cerclage in three of them
(21.5%). All three patients achieved pregnancies and after 36th weeks of
gestation delivered by cesarean section (100%). CONCLUSIONS: RVT alone is an
indication for LAC. Considering its success, LAC should be performed before any
miscarriage.
PMID- 29949271
TI - Two-step shoulder delivery method reduces the incidence of shoulder dystocia.
AB - OBJECTIVE: io compare two-step method ot shoulder delivery with one-step for the
maternal and neonatal outcomes. MATERIALS AND METHODS: This was a randomized
controlled clinical trial. Women scheduled for vaginal delivery without severe
complications were enrolled and randomly arranged into two groups. Women in study
group were delivered by two-step method for shoulder delivery, that is to wait
for at least one contraction after head delivery, and naturally delivery of
shoulder. Women in controlled group were delivered by one-step method, that is
after the head was delivered, gentle press of head was applied to facility
shoulder delivery. Maternal and neonatal outcomes as Apgar score, rate of
shoulder dystocia, and postpartum bleeding were recorded. Interval of head to
shoulder was timed in second. RESULTS: The study group had lower rate of shoulder
dystocia than that in control group (X2= 4.27,p =0.03), no increasing of
asphyxia, and postpartum bleeding. The average interval of head to shoulder in
study group was longer than that in control group. There was no difference in
interval between shoulder dystocia vs. normal birth group, neither was there a
difference in interval between asphyxia babies and normal babies group. By two
step method, the mean value of head to shoulder interval was 59.025 seconds, 95%
CI (20.000-150.000 seconds), mean+2xSD = 148.927 seconds. In one-step group, mean
was 44.172 seconds, 95% CI= (10.000~105.000 seconds), mean +2xSD = 94.812
seconds. CONCLUSION: Two-step method of shoulder delivery had a lower rate of
shoulder dystocia than one-step method, no increasing of neonatal asphyxia and
postpartum bleeding. The longer interval of head to shoulder did not relate to
shoulder dystocia and asphyxia. The normal value of head to shoulder interval
might be longer than 60 seconds.
PMID- 29949272
TI - Is early embryo cleavage a factor to increase success in all types of ICSI
indications?.
AB - PURPOSE: The authors aimed to compare early embryo cleavage with pregnancy rates
in intracytoplasmic sperm injection/embryo transfer (ICSI/ET) cycles due to male
infertility or tubal factor infertility (TFI). MATERIALS AND METHODS: 412
ICSI/embryo transfer cycles undergoing treatment for over two years were
prospectively analyzed; 337 of the cycles were due to male infertility, whereas
75 suffered from tubal factors. Non-early cleaved (NEC) embryos were used for ET
in 271 male factor and 67 tubal factor cycles, whereas early cleavage embryos
were used for embryo transfer in 66 male factor and eight tubal factor cycles.
RESULTS: In 66 out of 337 cycles (19.58 %) in male factor group and in eight out
of 75 tubal factor cycles (10.66%), early cleavage (EC) embryos were obtained (p
= 0.069). The clinical pregnancy rate was significantly elevated in EC subgroup
(34.8%) compared to NEC subgroup (20.6%) (p = 0.015) in the male factor
infertility group. The clinical pregnancy rate was non-significantly elevated in
EC subgroup (37.5%) compared to NEC subgroup (23.8%) (p = 0.410) in the TFI
group. CONCLUSIONS: The authors found that the implantation and pregnancy success
of EC embryos vary with the therapeutic indication. The success rate would be low
even with usage of EC embryos in untreated cycles of TFI.
PMID- 29949273
TI - Pain assessment during outpatient hysteroscopy using room temperature versus warm
normal saline solution as a distention medium - a prospective randomized study.
AB - OBJECTIVE: To assess the efficacy of warm normal saline distention solution
versus a standard, room-temperature normal saline as distention medium for pain
relief during outpatient hysteroscopy. MATERIALS AND METHODS: A prospective
randomized case-placebo controlled study was conducted in tertiary care centre -
Central Clinical Hospital of Ministry of Interior and Administration. Study group
consisted of 100 women referred for outpatient hysteroscopy between January 2015
and July 2015. Every patient, who was referred for an office hysteroscopy, was
offered to participate in the study to receive a sterile, 0.9% normal saline
warmed up to 360C as distention medium. Control group were women receiving
sterile, room temperature of 250C, 0.9% normal saline solution as a distention
medium. No pre-medication nor analgesia were used. A visual analogue scale (VAS)
was used for one-dimensional pain assessment. Women were asked to mark a VAS
score before, during, and five and 15 minutes following the procedure. RESULTS:
Median VAS scores during and directly after the anaesthesia-free hysteroscopy
were no different between two groups. (p = 0.554 and p = 0.121, respectively).
There were also no differences in the procedure time between groups (p = 0.845).
CONCLUSIONS: Warm normal saline distention solution does not reduce the pain
during and at the end of the outpatient hysteroscopy. The effect does not depend
on the age of women, menopausal status, parity or type of outpatient hysteroscopy
(operative or diagnostic).
PMID- 29949274
TI - Ghrelin to obestatin ratio in maternal serum in pregnancies complicated by
intrauterine growth restriction.
AB - Ghrelin, an endogenous for the growth hormone secretagogue receptor, has been
shown to participate in fetal growth. Obestatin, encoded by the same gene as
ghrelin, is described as a physiological opponent of ghrelin. This study was
designed to determine the changes of ghrelin/obestatin ratio in maternal serum in
pregnancies with intrauterine growth restriction (IUGR). The authors found that
the ghrelin levels in maternal serum were significent lower in IUGR group than in
control group (236.34 +/- 14.58 pg/ml vs. 321.49 +/- 18.19 pg/ml, p = 0.003).
However, the difference of obestatin levels in maternal serum in IUGR group than
in control group was not significent (276.25, +/-20.54 pg/ml vs. 256.34 +/- 21.21
pg/ml, p = 0.308). The ratio of ghrelin to obestatin in maternal serum were
significent lower in UGR group than in control group (1.05 +/- 0.09 vs. 0.82 +/-
0.08, p = 0.03). Meanwhile, the maternal serum growth hormone (GH) concentration
in IUGR group was lower than that in control group (1.08 +/- 0.08 pg/ml vs. 1.41
+/- 0.09 pg/ml, p = 0.009), and the maternal serum pla- cental growth hormone
(PGH) concentration in IUGR group was lower than that in control group (2.21 +/-
1.24 pg/ml vs. 2.92 +/- 0.27 pg/ml,p = 0.031). The ratio of ghrelin to obestatin
in maternal serum were positively correlation with GH and PGH concentrations in
IUGR group (r = 0.876, p = 0.52; r = 0.764, p = 0.64). The findings of this study
suggest that the ratio of ghrelin to obestatin in maternal serum were low, and
were positively correlated with GH and PGH concentration in IUGR group, which can
been considered as evidencees of ghrelin/obestatin balance disorder role in
pathogenesis of IUGR.
PMID- 29949275
TI - Immunohistochemical expression of MTA1 and MTA3 in placental tissue of normal and
preeclamptic pregnancies.
AB - PURPOSE: The aim of this preliminary study was to evaluate and compare MTAI
andMTA3 antigens expression in normal and preeclamptic placentas in order to
demonstrate their possible functional relationship during pathogenesis of
preeclampsia. MATERIALS AND METHODS: A series including 20 paraffin-embedded
placentas, ten of which originated from normal patients and ten from preeclamptic
patients, that were examined by immunohistochemistry using the polyclonal
antibodies MTAI and MTA3. RESULTS: The results of this study showed a positive
nuclear staining reaction against MTAI and MTA3 in both normal and preeclamptic
placentas. However, in preeclamptic chorionic villi, cytotrophoblast and
syncytiotrophoblast cells demonstrated increased expression of MTAI and MTA3 than
in normal ones. CONCLUSION: The present observations indicate a potential role
for MTAI and MTA3 for normal human placental function, playing an essential role
in the pathogenesis of preeclampsia. Nevertheless, the precise relationship
between these antigens' expression and pathological pregnancies remains to be
elucidated.
PMID- 29949276
TI - Management of placenta accreta in an Australian tertiary referral centre: a ten
year experience.
AB - PURPOSE OF INVESTIGATION: To report a ten-year experience in management of a
highly morbid obstetrical condition in placenta accreta (PA) at a tertiary
referral centre, uniquely equipped with an integrated Interventional Radiology
theatre, with a primary aim to guide best practice. MATERIALS AND METHODS:
Retrospective analysis of all histologically proven PA cases at a tertiary centre
in Australia between January 2004 and December 2013. Medical records were
reviewed for obstetrics history, operative details, post-operative management and
neonatal outcome. RESULTS: Sixteen cases of PA were identified during the tinie
period; 75% had identifiable risk factors for PA and 87.5% of patients were
diagnosed antenatally. Mean gestational age at time of delivery was 34 +/-3.4
weeks. Ten cases were performed electively, while the remaining underwent
emergency caesarean section. One patient was managed conservatively with placenta
left insitu; time to complete resolution of placenta was 71 days. Among patients
who underwent hysterectomy (15/16), the proportion of total (n=8) vs. subtotal
(n=7) hysterectomy was similar. Average operating time was 123 +/- 45.9 minutes.
Compared to emergency cases, patients who underwent elective surgery had
significantly lower blood loss (2.2 vs. 3.1 L, p < 0.05). Common iliac artery
balloons were deployed in eight cases, with a non-statistically significant
reduction in intraoperative blood loss (2 vs. 3.2 L, p < 0.05). Fifty percent of
patients required ICU admission. Neonatal survival at six months was 93.75%
(15/16). CONCLUSION: The present report demonstrates the importance of timely
diagnosis and comprehensive preparation in the surgical management of patients
with placenta accreta. The availability of relevant services in the peri
operative phase, including: obstetricians, interventional radiology facility and
personnel, intensive care, and neonatology teams, are crucial in achieving
optimal outcome for the patient and neonate. In line with reports in the
literature, the authors advocate a team-based multidisciplinary approach in a
tertiary-level centre for management of this high-risk condition.
PMID- 29949277
TI - Interobserver reliability of sonographic fetal biometry in second trimester
maternal serum screening.
AB - PURPOSE: To examine the interobserver variability for fetal biometry parameters
and to investigate whether this variability affects the second-trimester maternal
serum screening test (STMSS) results. MATERIALS AND METHODS: A total of 60
singleton pregnancies who were scheduled for STMSS were investigated. Two
experienced sonographers performed all examinations at the same visit. The risk
calclations of screening were performed according to the each operator's
biometric measurements separately. Interobserver variability in measurements of
fetal biometrics and the effect of this interobserver variability on the
screening results were assessed. RESULTS: inter-observer reliability for
biparietal diameter (BPD) and femur length (FL) were 0.904 and 0.888 (p < 0.00
1), respectively. interobserver reliability coefficients for trisomy 21, trisomy
13/18, and neural tube defect were 0.887, 0.999, and 0.920 (p < 0.0001),
respectively. CONCLUSION: The present results demonstrate that the interobserver
reliability and agreement of ultrasound measurements of fetal biometry in cases
of routine prenatal screening are highly reliable.
PMID- 29949278
TI - IVIg therapy increases delivery birthweight in babies born to women with elevated
preconception proportion of peripheral blood (CD56+/CD3-) natural killer cells.
AB - : In this study, the authors investigated: (1) whether elevated preconception
peripheral blood proportion of CD56+/CD3- lymphocytes (NK cells) was associated
with low delivery birthweight in high risk women, and (2) whether intravenous
immunoglobulin (IVIg) therapy could be used to improve the delivery outcome in
these women. MATERIALS AND METHODS: Sixty-six women who had singleton deliveries
were divided into four groups. Group 1: 16 women with elevated preconception NK
cells (>12%) using IVIg, group 2: eight women with similar elevated preconception
NK cells not using IVIg, group 3: 32 women with non-elevated preconception NK
cells (<=12%) using IVIg, and group IV: ten women with similar non-elevated
preconception NK cells not using IVIg. These groups were similar with regards to
patient age, test results, and history. RESULTS: Mean gestational age (+/-cmaz,
GSD) of babies at delivery wa+/- 39.3 +/- 1.7+/- 37.4 +/- 3.7+/- 38.5 +/- 1.3,
an+/- 38.7 +/- 1.5 weeks, for groups 1, 2, 3 and 4, respectively. Mean
birthweight of babies at delivery was+/- 3,267 373,+/-2,654 +/- 627,+/-3,129 +/-
527, and+/-3,202 +/- 357 grams, respectively. Birthweight was significantly
higher for1group I vs. group 2 (p = 0.006) but not for groups 1 vs. group 3.
There was no significant difference between the groups for preeclampsia rate, C
section rate or preterm delivery rate. CONCLUSION: In women with elevated
preconception peripheral NK cells, mean birthweight at delivery is low without
IVIg therapy +/-2,654 +/- 627 grams) but significantly improved with IVIg therapy
+/-3,267 +/- 373 grams). In high risk wom without preconception NK cell
elevation, mean birthweight at delivery is not further-increased with IVIg
therapy +/-3,202 +/- 357 grams with IVIg vs.+/-3,129 +/- 527 grams without IVIg).
IVIg may be a treatment option for women with preconception NK elevation at risk
of a low birthweight baby. Preconception immune testing may be a tool for
determining which patients will benefit from IVIg therapy. Larger repeat studies
are needed for confirmation.
PMID- 29949279
TI - Cytogenetic analysis of 10,286 cases with male infertility.
AB - PURPOSE: Chromosome analysis of 10,286 cases with male infertility and to discuss
the genetic causes of male infertility. MATERIALS AND METHODS: 10,286 patients
with azoospermia and oligoasthenozoospermia were collected in the present center
from January 2009 to January 2013.Peripheral blood lymphocyte culture and
chromosome analysis were performed. RESULTS: In all the 10,286 cases with
azoospermia and oligoasthenozoospermia, 8,401 cases showed normal karyotype, 538
cases had chromosome polymorphism, accounting for 5.2% and 1,378 cases had
chromosomal abnormalities with a frequency of 13.4%; Conclusions: Genetic factors
are closely related to the occurrence of azoospermia and oligoasthenozoospermia,
and chromosome analysis in patients with male infertility is necessary.
PMID- 29949280
TI - Perinatal outcomes of sonographically detected nuchal cord in southeastern
Turkey.
AB - PURPOSE: To investigate the outcomes of pregnancies with a sonographically
detected nuchal cord (NC) from a single center in south-eastern Turkey. MATERIALS
AND METHODS: A retrospective study was carried out at Maternity and Child Health
Hospital Diyarbakir, Turkey, between 2011 and 2013. A-total of 477 pregnancies
with sonographically detected NC during the second and third trimesteri of
gestation (20-40 weeks) were included. The control group consisted of 1,043
randomly selected pregnancies without NC matched for gestational age at the time
of ultrasound examination. Outcome variables, including maternal age, parity,
gestational age at delivery, mnode of delivery, intrapartum fetal heart
abnormalities, meconium-stained amniotic fluid, birth weight, and one- and five
minute Apgar scores, were compared between the two groups. RESULTS: There were no
statistically significant differences in any of the outcome variables between
patients with sonographically detected NC and controls. CONCLUSIONS: The presence
of NC indicates a need for increased care but is not associated with adverse
perinatal outcomes.
PMID- 29949281
TI - May supplementation of coenzyme Q10 help prevent development of hydatidiform
mole?.
AB - OBJECTIVE: The pathological mechanisms of gestational trophoblastic disease have
not yet been clearly determined. It is thought that oxidative damage contributes
to the process. The aim of this study was to determine the levels of coenzyme Q10
(CoQ 10), DNA damage, and lipid peroxidation in patients with hydatidiform mole.
MATERIALS AND METHODS: The authors studied the levels of CoQ10, 8
hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) by high-performance liquid
chromatography (HPLC), and the activity of glutathione peroxidase (GPX) by
spectrophotometric method in blood obtained from patients with a complete
hydatidiform mole (n=29), healthy pregnant women (n=29), and healthy non-pregnant
women (n=29). RESULTS: The 8-OHdG/dG ratio (2.8148 +/- 0.81592) and MDA (10.8341
+/- 4.64875 MUmol) were significantly higher in patients with complete
hydatidiform mole, while the ubiquinol-10/ubiquinone-10 ratio (0.2107 +/-
0.15675) and GPX activity (43.4606 +/- 18.31694 mU/mI) were lower (p < 0.001).
CONCLUSION: The authors suggest that both mitochondrial oxidative and oxidative
DNA damage play important roles in the pathogenesis of complete hydatidiform
mole. Therefore supplementation of CoQ10 prevents recurrent gestational
trophoblastic disease.
PMID- 29949282
TI - Occurrence of climacteric symptoms in postmenopausal women after prophylactic
bilateral ovariectomy.
AB - PURPOSE OF INVESTIGATION: To analyse the quality of life in postmenopausal women
after prophylactic bilateral ovariectomy depending on the time from menopause.
MATERIALS AND METHODS: The study involved 252 postmenopausal women grouped
according to the time from last menstruation: one to five years (group A), five
to ten years (group B), and > ten years (group C). All women were ovariectomized
during laparotomy performed for benign diseases of the uterus. Climacteric
symptoms were measured with the Kupperman Index one day before and three months
after surgery. RESULTS: Highly significant age differences and no substantial BMI
differences were demonstrated among the study groups. Before and after surgery
climacteric symptoms were reported by 17.06% and 57.8% of women, respectively.
After surgery, group A women significantly more often had hot flushes, sweating,
nervousness, and sleep disorders, the women in group B significantly more often
reported sleep disorders, nervousness, and sweating, and the women in group C
significantly more often complained of nervousness. CONCLUSION: In postmenopausal
women, ovaries play the most important role during the first ten years from the
last menstruation.
PMID- 29949283
TI - Ultrasonography of fetal cleft lip and palate in first-trimester.
AB - PURPOSE OF INVESTIGATION: To explore the ultrasonographic methods towards cleft
lip and palate (CLP) in first-trimester. MATERIALS AND METHODS: 3,795 fetuses
were scanned for facial structures including cross section of upper alveolar
process, oblique coronal section of upper lip, and postnasal triangle section
when measuring nuchal translucency (NT). The abnormal cases underwent
ultrasonography for clear diagnosis at 17-18 gestational weeks (GWs), while the
negative cases underwent systemic ultrasonography at 20-26 GWs, and followed up
until birth. RESULTS: Among the 3795 fetuses, 16 cases had CLP, with an incidence
rate as 4.2%; 12 were detected in first trimester, with a detection rate of 75%,
and the detection rate of bilateral CLP was 100%, four were missed, with a
misdiagnosis rate of 25%, and 12 cases examined at 17-18 GWs met first-trimester
diagnosis. Among the four missed cases, two were diagnosed with systemic
ultrasonography, and two were diagnosed postnatally. All cases were confirmed
after induction of labor or after birth. CONCLUSIONS: Ultrasonography in first
trimester could diagnose severe case of CLP.
PMID- 29949284
TI - Responsiveness of the Endometriosis Health Profile-30 questionnaire in a Swedish
sample: an observational study.
AB - OBJECTIVE: The objective was to evaluate the responsiveness of the Endometriosis
Health Profile-30 (EHP-30) questionnaire in a Swedish sample. MATERIALS AND
METHODS: Forty-two patients with endometriosis were included in a prospective
observational study. MAIN OUTCOME MEASURES: The changes on the EHP-30
questionnaire after pertubation treatment were compared with the patients' self
estimated change in pain intensity. The responsiveness to change was evaluated
with effect sizes and significance of change (paired t-test). The changes in
scores between those who improved / not improved were compared with independent t
test. RESULTS: The changes in the scores were significant for all dimensions on
the core questionnaire (p = 0.04-0.0002) for improved patients in contrast to the
patients in the stable group where there were no significant changes in any
dimension (p = 0.16-0.63). The effect sizes were large (> 0.8) on all core scales
except for self-image (0.51) for the improved patients and small on all scales in
the non-improved (stable) group (- 0.17-0.35). There were significant differences
between the improved and the stable group considering change in most of the core
EHP-30 scores. CONCLUSIONS: The EHP-30 is responsive to improvement on all core
scales and is acceptable, understandable, and applicable in this Swedish sample.
PMID- 29949285
TI - Alteration of serum endocan in normal pregnancy and preeclampsia.
AB - : Endocan is a novel marker for inflammation but its significance in preeclampsia
remains unknown. OBJECTIVE: The aims of this study were to delineate the changes
of maternal endocan in normal pregnancy and preeclampsia and to explore its
possible role in the pathogenesis of preeclampsia. MATERIALS AND METHODS: Blood
samples were taken from 42 non-pregnant women, from 43 normal pregnant women at
third trimester, and from 41 preeclamptic women. Serum endocan levels were
determined with enzyme-linked immunosorbent assay (ELISA) and compared among the
groups. RESULTS: There were no significant differences in serum endocan among non
pregnant women, normal pregnant women, and women with preeclampsia (X2= 2.207, p
= 0.137) and there was no significant difference in serum endocan between women
with mild and severe preeclampsia (Z= 0.368, p = 0. 713). The authors concluded
that serum endocan did not change in pregnancy and preeclampsia, indicating
endocan may not be involved in the pathogenesis of preeclampsia.
PMID- 29949286
TI - Fetal hydrops and middle cerebral artery Doppler in prediction degree of fetal
anemia and the best timing for therapy.
AB - PURPOSE: To determine the role of fetal multiples of the median of middle
cerebral artery peak systolic velocity (MoM MCA-PSV), in predicting the degree of
fetal anemia for determination of the best timing for the second intrauterine
intravascular transfusion (IUIVT) in hydropic fetuses with Rh alloimmunization.
MATERIALS AND METHODS: Prospective study of 30 monofetal pregnancies with
maternal Rh D alloimmunization and hydrops fetalis, from 2005 to 2012 that
underwent first and second IUIVT were assessed. RESULTS: Thirty IUIVT were
performed at 26.9 weeks (standard deviation, SD 4.3). Mean interval to the second
procedure was 11.23 (SD 6.21) days and average hematocrit decline rate was
1.45%/day. The study did not demonstrated statistical significance between MCA
MoM-3 before the second IUIVT, and the mean decline rate in fetal hematocrit
levels (expressed in percentage/day) r = 0.220; p = 0.242, and between MCA-MoM-3
and the time interval between both procedures (T) r = -0.157; p = 0.408.
CONCLUSION: The measurements fetal MoM-MCA before every IUIVT cannot be useful as
predictor for the best timing for the next IUIVT, but it can be useful in
predicting severity of fetal anemia.
PMID- 29949287
TI - The prevalence of abnormal vaginal flora and predictive factors for intrauterine
infection in pregnant Korean women with preterm labor.
AB - OBJECTIVE: To investigate the prevalence of abnormal vaginal flora (AVF) and
predictive factors for intrauterine infection in pregnant Korean women with
preterm labor. MATERIALS AND METHODS: The authors reviewed the medical records of
106 pregnant Korean women with preterm labor admitted to Eulji Medical Center
between January 2006 and August 2011. The results of vaginal discharge tests and
maternal serum C-reactive protein (CRP) level at admission, placental biopsy, and
perinatal outcomes were searched. The prevalence of abnormal vaginal flora was
calculated. The perinatal outcomes and predictive factors for intrauterine
infections were analyzed based on placental pathology and early-onset neonatal
sepsis. RESULTS: The prevalence of abnormal vaginal flora was 75.4%. Ureaplasma
urealyticunz (UU), intermediate flora, Candidiasis, bacterial vaginosis, and
aerobic bacterial colonization were detected in 40.6%, 38.7%, 17%, 14.2%, and
11.3% of the women, respectively. The frequency of early-onset neonatal sepsis
was significantly different between women with aerobic bacterial colonization and
those with normal flora (p = 0.008). An elevated maternal serum CRP level was an
independent intrauterine infection predictor (odds ratio, 1.918; 95% confidence
interval, 1.102-3.338; p = 0.048). CONCLUSION: Aerobic bacterial colonization may
predict early-onset neonatal sepsis. An elevated maternal serum CRP level was an
independent intrauterine infection predictor based on placental infections and
early-onset neonatal sepsis.
PMID- 29949288
TI - Construction and identification of a model for HJURP gene defect expression in
human embryo villus cells.
AB - OBJECTIVES: To construct a lentiviral vector for RNA interference (RNAi) of the
HJURP gene and to identify the silencing efficiency in the human embryo villus
cells and to provide a human embryo villus cells multiplication and chromosome
segregation. MATERIALS AND METHODS: In accordance with the study, three specific
sequences of siRNA targeting HJURP gene were designed, synthesized, then the
complementary DNA containing both sense and antisense oligonucleotides of the
targeting sequences were annealed and inserted into the lentiviral vector.The
correct clonings were confirmed by PCR and sequencing. The most effective
recombinant lentivirus vector was screened, and the recombinant plasmids with the
lentivirus packaging mixes were co-transfected into 293T cells to obtain packaged
lentivirus particles. Then viral titer was determined. The silencing efficiency
of target gene in human embryo villus cells was detected by Real-Time PCR.
RESULTS: DNA sequencing showed that the shRNA sequence was successfully inserted
into the lentivirus vector. The recombinant lentiviral vector was successfully
transfected into 293T cells. The recombinant lentivirus had a titer of 108
PFU/ml. After silencing HJURP gene in human embryo villus cells, the expression
level of HJURP mRNA decreased significantly and the RNAi efficiency was greater
than 70%. CONCLUSION: A lentiviral shRNA expression vector targeting the HJURP
gene was successfully constructed and may effectively silence the target gene at
a cellular level, which provides a experimental model for the influence of HJURP
gene expressing inhibition on human embryo villus cells multiplication and
chromosome segregation.
PMID- 29949289
TI - Software toolbox for analysis of the endometrial myometrial junction - a pilot
study.
AB - PURPOSE: To develop and evaluate an algorithm for computerized evaluation and
measurement of the endometrial-myometrial junction (EMJ). MATERIALS AND METHODS:
The advanced image processing toolbox of the Matlab software package was used for
identificiation and quantitative analysis of the EMJ area on three-dimensional
(3D) rendered coronal plane uterine images, with clear-cut borders of the EMJ.
The algorithm was used to process the images and calculate the geometric
parameters characterizing the identified EM The manual measurements of the
maximum thickness of the EMJ were compared to automated measurements performed by
the algorithm on the same images. RESULTS: For all three interfaces, the mean
maximum manual measurement was less than the mean maximui computed measurement.
The differences between the two measurements were not statistically significant
(p = 0.275, 0.608 and 0.41 for the right wall, left wall, and fundus,
respectively). The mean systematic and random errors ranged from 5.4% tol9.3% and
20.4 to 48.6%, respectively. Pearson correlations for the right wall, left wall
and fundus (r = 0.642, p = 0.001; r = 0.730, p < 0.001, and r 0.694, p < 0.001,
respectively) were good. CONCLUSIONS: Maximum EMJ thickness measurements
performed by the innovative Matla software algorithm are as accurate as manual
measurements, and have the potential to reduce inter-observer variability.
PMID- 29949290
TI - The importance of some angiogenic markers in spontaneous abortion.
AB - AIM: In this study, the authors aimed to determine the serum levels of vascular
endothelial growth factor (VEGF), angiopoietin-l (ang-1) and angiopoietin-2 (ang
2) factors as indicators of placental angiogenesis and vasculogenesis in abortion
cases. Materials and Meth- ods: This study was conducted in 40 women who were
pregnant for 7-20 weeks and diagnosed with an incipient abortion and 40 pregnant
healthy women with similar ages, gestational weeks, and body mass index (BMI)
values. Serum VEGF, ang-1, and ang-2 levels were measured with ELISA methods.
RESULTS: The authors found that the serum VEGF levels were higher and ang-1
levels were significantly lower in pregnant women whose pregnancies failed with
abortion, compared to control group. There was no significani difference in terms
of ang-2 levels between groups. CONCLUSION: A strong relationship was found
between VEGF and ang-I early pregnancy loss, and significant changes of these
factors may also be associated with the physiopathology of abortion incipience.
Evaluating these factors may be benefical for prediction and designing of
treatment modalities on spontaneous abortion.
PMID- 29949291
TI - Effect of maternal pregnancy-induced hypertension on neonatal immunity.
AB - OBJECTIVE: To explore the effect of pregnancy-induced hypertension (PIH) on
immune system of neonate. Materials and Methods Sixty neonates whose mothers
suffered from PIH were selected and divided into preeclampsia group (n=28) and
gestational hyperten sion (GH) group (n=32) according to severity of mother's
condition. Thirty neonates having healthy mothers were enrolled as control group.
The base clinical characteristics of neonates were collected and umbilical vein
blood was drawn to detect the distribution of lymphocyte antigen, immune
globulin, and complement level. RESULTS: The gestational week, birth weight, head
circumference, and one minute Apgar score of both PIH groups were lower than
those of control group, and preeclampsia group was lower than GH group (p <
0.05). There was significant difference between preeclampsia group and control
group in blood, routine and blood glucose levels Concerning blood glucose levels,
both PIH groups were lower than control group, and preeclampsia group was lower
than GH group (p < 0.05). Content of IgG and complement C4 of GH group was lower
than those of control group; IgG level of preeclampsia group was also lower than
GH group (p < 0.05). CONCLUSIONS: PIH of pregnant mother affects the immunity of
neonate, and more severe PIH will more negatively affect immunity of neonate.
PMID- 29949293
TI - Successful management of complete placenta previa after intrauterine fetal death
in a second-trimester pregnancy by uterine artery embolization: case report and
literature review.
AB - A 27-year-old woman with complete placenta previa was referred at 22 weeks of
gestation because of vaginal bleeding and fetal growth restriction. At 24 weeks,
sudden fetal death occurred, but bleeding continued and transvaginal sonography
revealed abundant periplacental blood flow in the uterine wall. To avoid cesarean
section, the authors performed uterine artery embolization (UAE) be- fore vaginal
delivery of the fetus. Subsequently, there was little bleeding when laminaria was
inserted for cervical ripening and the fetus was delivered vaginally by using
vaginal gemeprost. Total blood loss was only 149 ml. The present case suggests
that UAE may be an option for patients with placenta previa who desire vaginal
delivery after intrauterine fetal death (IUFD) in a second-trimester pregnancy.
PMID- 29949292
TI - Protective effect of curcumin on ovarian reserve in a rat ischemia model: an
experimental study.
AB - PURPOSE OF INVESTIGATION: To determine the protective effect of curcumin on
ovarian reserve in a rat ischemia model. MATERIALS AND METHODS: Thirty female
Albino rats were randomly divided into two groups by time of unilateral, left
ovary ischemia/reperfusion (group 1: two-hour ischemia / two-hour reperfusion;
group 2: four-hour ischemia / four-hour reperfusion). Each group was subdivided
into three subgroups, sham, control, and curcumin (intraperitoneal curcumin (200
mg/kg) simultaneously with reperfusion). Histological grading of ischemic indices
of paraffin-embedded ovarian tissue using hematoxylin and eosin (H&E), and anti
Mulerian hormone (AMH) levels by enzyme-linked immunosorbent assay (ELISA), were
measured 40 days later. RESULTS: No difference was found between groups 1 and 2
or among subgroups within either group for right and left ovary grades. AMH
levels were significantly higher in the curcumin subgroup compared to sham and
control within group 2 and in group 2 versus group 1 curcumin subgroups.
CONCLUSION: Curcumin maintains and protects ovarian functions in an ischemia
reperfusion rat model.
PMID- 29949294
TI - Placenta percreta with colon involvement in a twin pregnancy: case report and
literature review.
AB - A case of a woman with twin pregnancy having placenta percreta involving the
colon, showed hematochezia symptoms, experienced bleeding which caused the
patient's mortality. Placenta percreta with bowel involvement is a very serious
complication of pregnancy. Symptoms are very atypical and it is very difficult to
diagnose.
PMID- 29949295
TI - Post-partum management of severe pubic diastasis.
AB - INTRODUCTION: Pubic symphysis diastasis during pregnancy is a rare complication
which can present as pain with ambulation, urinary dysfunction, and pelvic
instability. A consensus treatment does not currently exist between surgical and
conservative management. The authors present a case of severe pubic diastasis
which was successfully treated using a conservative pelvic binder. CASE REPORT: A
31-year-old female presented with severe lower back pain following the uneventful
delivery of her fourth child. On radiograph, a pubic symphysis diastasis of 5.5
cm was noted and she was subsequently fitted with a pelvic binder on post-partum
day 3. She experienced a full range of motion and was pain free at six-week
follow-up, with a diastasis of 2.1 cm present. At one year and three-month follow
up, the patient presented with a diastasis of 2.4 cm and continued to have full
range of motion and mobility. CONCLUSION: This case contributes to the literature
in showing that conservative treatment of pubic diastasis could be considered in
cases where separation has exceeded normal physiologic limits.
PMID- 29949296
TI - Successful live birth in a patient who underwent cranial radiotherapy and
systemic chemotherapy by implantation of a cryopreserved blastocyst on day 7.
AB - Preservation of fertility has been recommended for cancer-bearing patients of
reproductive age before undergoing cancer treatment. However, there are many
considerations and it is difficult to preserve fertility for all patients
undergoing therapy for malignancies. Female cancer survivors had lower pregnancy
and live birth rates compared with others that underwent assisted reproductive
technologies (ARTs). We should continue to consider the issue of infertility in
patients who underwent therapies for malignancies. This is the first report of a
successful live birth in a patient with a cranial tumor who underwent
radiotherapy and chemotherapy after implantation of an autologous embryo. The
patient was a 27-year-old Japanese woman. She was diagnosed with suprasellar
germinoma at 13 years of age, and she developed panhypopituitarism after
radiotherapy and chemotherapy. At 27 years of age, she began infertility
treatment with in-vitro fertilization (IVF). The level of anti-Mallerian hormone
(AMH) was 4.29 ng/ml. After ovarian stimulation by high purified human menopausal
gonadotropin (HP-hMG), she obtained two blastocysts and became pregnant by
implantation of a cryopre- served blastocyst. At 37 gestational weeks, she
delivered a healthy female baby by cesarean section.
PMID- 29949297
TI - Mature ovarian cystic teratoma containing well-differentiated cerebellar tissue.
AB - A 38-year-old female patient experienced groin pain; ultrasound imaging revealed
a dermoid cystic mass in the right ovary and a cystectomy was then performed.
Unusually, a mature cerebellum is found in the cyst wall. The pathological
diagnosis was 'mature cystic teratoma with well-differentiated cerebral and
cerebellar tissue'. Glial tissue is a common neural component of teratomas, but a
cerebellum is extremely rare in mature ovarian cystic teratomas. The authors
report the case because of its rare component; they acknowledge that a cystic
teratoma is the most common neoplasm of ovarian germ cells.
PMID- 29949298
TI - Bladder stone formation on permanent suture material ten years after laparoscopic
high uterosacral ligament suspension.
AB - The present authors describe an uncommon case of iatrogenic bladder stone
formation in a patient who underwent surgery for pelvic organ prolapse. A female
patient who underwent high uterosacral ligament suspension ten years ago
presented with pyuria and irritable bladder symptoms that did not respond to
treatment. She had not experienced any specific urinary symptoms during the
previous ten years. Patient evaluation revealed bladder stone formation on the
non-absorbable suture material used during the previous operation. Cystoscopy
during the previous operation did not find the suture material, and the suture
knot that was tied extravesically during the operation was found inside the
bladder. These strongly suggest delayed migration and rotation of the'suture knot
after surgery rather than direct penetration of the bladder during operation.
Delayed suture migration is a long-term complication that clinicians should
consider in a patient who suffers from recurrent urinary symptoms after pelvic
surgery around the bladder.
PMID- 29949299
TI - Spontaneously closed gastrocutaneous fistula becomes symptomatic after 30 years
with pregnancy.
AB - Percutaneous endoscopic gastrostomy (PEG) is the standard procedure of choice for
the provision of enteral nutrition in children who require long-term nutritional
support. Removal of gastric tubes has a risk of causing gastrocutaneous fistula
and this complication is dealt within childhood. The authors report a 34-year old
woman who had a PEG procedure at the age of four years due to caustic esophageal
injury and recovered without incident. Thirty years later she becomes pregnant
and as her pregnancy progresses, her former fistula opening becomes more obvious
and at the 34'h week of the pregnancy she' presents to the hospital with fistula.
After a successful delivery, the fistula was evaluated and repaired surgically.
PMID- 29949300
TI - Medical management of early pregnancy failure with misoprostol with rupture of
the cesarean section scar pregnancy.
AB - PURPOSE: To report a case of ruptured uterus in the first trimester with the use
of misoprostol for early pregnancy tailure in a woman with unrecognized cesarean
section scar pregnancy. CASE: A 27-year-old woman, gravida 5 para 3+1, presented
with abdominal pain and vaginal bleeding. Transvaginal ultrasonography revealed a
fetus without fetal heart activity at nine weeks gestation, making the diagnosis
of early pregnancy failure. Her previous deliveries were by cesarean section. She
was managed medically with misoprostol. Seven hours after misoprostol
administration, she developed sudden onset of severe abdominal pain. Repeat
transvaginal ultrasonography diagnosed cesarean section scar pregnancy.
Laparotomy revealed hemoperitoneum with rupture of cesarean section scar
pregnancy. Subtotal hysterectomy was performed. CONCLUSIONS: Failure to recognize
cesarean section scar pregnancy can result in a ruptured uterus in the first
trimester with the use of misoprostol for early pregnancy failure. Increased
awareness of the unexpected consequences of cesarean section is of paramount
importance.
PMID- 29949301
TI - Pericardial tumor and pregnancy - a case report study.
AB - Primary benign and malign pericardial ind heart tumors are very rare (0.002
0.03%). Benign tumors of heart and pericardium are more frequent (myxoma,
rhabdomyoma, lipoma, and papillary fibroelastoma of endocardium: 70% of all
primary tumors). Because of low frequency, clinicians rarely and hardly diagnose
these types of tumors. The affected patients wander from one healthcare center to
another, usually with misleading diagnosis, such as cardiomyopathy or mitral
stenosis. Pericardial and cardiac tumors cause pressure to surrounding
structures. Because of the specific anatomy and function, all heart tumors are
"malign by localization". Presence of benign pericardial tumor leads to
pericardial effusion, fibrinohemorrhagic pericarditis, and cardiac tamponade. In
the present study, the authors report a case of a female patient with pericardial
cyst which was diagnosed during the second trimester of pregnancy. After
undergoing multiple diagnostic procedures in short time period, the authors had
accurate set of definitive diagnosis. The patient had successful surgical
treatment and the pregnancy was continued until term without any fetal
consequences.
PMID- 29949302
TI - Isolated left descended inguinal ovary with ipsilateral ectopic pelvic kidney: a
case report and review of literature.
AB - Isolatd descended inguinal ovary is a rarity, but it should be considered as a
differential diagnosis of an inguinal mass at any age; in particular during
female infancy and up to adulthood. Herein the authors report a case of
asymptomatic isolated left descended inguinal ovary, with ipsilateral left
ectopic pelvic kidney that was accidentally discovered a few years after
menarche.
PMID- 29949303
TI - Successful management of primary splenic pregnancy: a case report and review of
literature.
AB - Ectopic pregnancy is defined as dislocation of a fertilized ovum anywhere other
than in the cavity of uterus. Generally, the common site for dislocation is
within fallopian tube, accounting for 95.5% of all ectopic gestations. Abdominal
pregnancy is rare with a potentially life-threatening variation that resides
within peritoneal cavity and the primary splenic pregnancy is even rarer. This
report describes a patient with primary splenic pregnancy, who was successfully
managed after splenectomy.
PMID- 29949304
TI - Should sexual intercourse be avoided during the embryo transfer cycle? Life
threatening ruptured heterotopic pregnancy after single thawed embryo transfer:
case report and review of the literature.
AB - BACKGROUND: To report the life-threatening complication of a raptured heterotopic
pregnancy occurring from thawed single embryo transfer. CASE REPORT: A 33-year
old woman underwent in vitro fertilization (IVF) under a step-up regimen. After
oocyte collection, blastocysts were frozen, and a single frozen-thawed blastocyst
was then transferred according to the natural cycle. On day 17 after embryo
transfer, an intrauterine pregnancy was confirmed. On day 28, she complained of
sudden abdominal pain and ultrasonography revealed marked fluid retention in the
peritoneal cavity. Emergency laparoscopy was performed, revealing hemoperitoneum
and a ruptured interstitial heterotopic pregnancy (HP), which was then resected
laparoscopically. Because sexual intercourse had occurred shortly before the
transfer, a HP comprising a spontaneous pregnancy and a pregnancy achieved by
assisted reproductive technology was assumed. The fetus in the uterus survived
and was delivered. CONCLUSION: In this case, however, despite the single embryo
transfer during the natural-cycle frozen-thawed embryo transfer process, the risk
of life-threatening complication as a HP as a consequence of spontaneous
pregnancy after sexual intercourse remained.
PMID- 29949305
TI - Unusual twin pregnancy: complete hydatidiform mole with coexistent normal fetus.
AB - The authors present a case of complete hydatidiform mole and coexisting fetus
(CHMCF) in which mole gestation caused a placenta previa; with a posterior
preterm premature rupture of membranes (PPROM) and ending in the 28h week of
gestation due to acute chorioamnionitis, obtaining a live preterm newborn.
PMID- 29949306
TI - Successful treatment of very PPROM caused by bipolar cord coagulation in acardiac
twin.
AB - The authors report management of a woman with an acardiac twin pregnancy
complicated by preterm premature rupture of the membrane (PPROM) for more than
two months after intrauterine treatment with bipolar cord coagulation at 24 weeks
of gestation.
PMID- 29949307
TI - A case report of fetal malignant immature mediastinal teratoma.
AB - PURPOSE: Fetal immature mediastinal teratoma is a rare disease. The pressure
generated by the tumor mass can cause hydrops fetalis, pulmonary hypoplasia,
pleural and peritoneal effusion, and polyhydramnios which cause the death of the
fetus. Routine prenatal ultrasound has enabled accurate diagnosis. MATERIALS AND
METHODS: The authors report a 26-year-old patient, gravida 4 para 1, who was
referred to this hospital, carrying a fetus with immature mediastinal teratoma.
RESULTS: At 27 weeks of gestation, a routine prenatal ultrasound suggested the
fetus had a mass at the anterior mediastinum, accompanied by pulmonary
hypoplasia, pleural and peritoneal effusion, subcutaneous edema of head and
chest, and polyhydramnios. After the therapeutic abortion, the gross anatomy
confirmed the mediastinal mass. The histological examination showed that the mass
was a grade 2 immature teratoma. CONCLUSIONS: The mother of the fetus had been
exposed to plaster, paint, and paint-thinner in the first trimester of pregnancy,
suggesting that these chemical contacts may be one of the causes of the disorder.
PMID- 29949308
TI - Did Richard III pray to Saint Apollonia for relief from toothache?
AB - Richard III is known to have had a particular devotion to St Apollonia who is the
Patron Saint of sufferers from toothache. The dentition in his skeleton exhumed
from a car park in Leicester shows missing teeth which are thought to have been
extracted due to caries. It is suggested that Richard, when he was Duke of
Gloucester, had prayed to St Apollonia for the relief of toothache before
submitting to undergo dental extractions.
PMID- 29949309
TI - Whence the Maryland Bridge? The evolution of the adhesive bridge.
AB - The evolution of the adhesive bridge technique from perforated retainers in the
anterior to its application in the posterior and how this led to development of
methods to bond directly to metal are detailed below. The parallel nature of
bonded bridges evolution in the US and Japan are noted.
PMID- 29949310
TI - Nazi Dental Gold: From Dead Bodies to a Swiss Bank.
AB - The removal of teeth containing gold fillings was part of the procedure in the
concentration camps during WWII. This paper describes the part played by Nazi
doctors and dentists.
PMID- 29949311
TI - The Faculty of Dental Surgery of the Royal College of Surgeons of England: An
overview of the first 70 year's achievements.
AB - The events leading up to the founding of the Faculty of Dental Surgery of the
Royal College of Surgeons of England are described. The role of the FDS in
establishing the training for dental specialties and research is recorded.
PMID- 29949312
TI - Reflections on dentistry and dental problems under the Third Reich.
AB - Victor Klemperer was a Professor of Romance Languages and Literature in Dresden
during the 1920s and 1930s. He kept a diary and the entries for the period 1933
to 1945 have been examined for references relating to dentistry and dentists.
These give an insight into an aspect of the social life of the period that
appears to have been previously largely overlooked.
PMID- 29949313
TI - European Federation of Periodontology-the first twenty-five years: periodontal
health for a better life.
AB - The European Federation of Periodontology (EFP), founded in 1991, has become one
of Europe's foremost dental organisations and a global force in the field of
Periodontology, including implant dentistry. This paper records the many,
different achievements of the EFP in its short but selfless and highly successful
contributions to the Federation.
PMID- 29949314
TI - Hospitalizations of Diabetes Ambulatory Care Sensitive Condition - Universal
Coverage Scheme at a Referral Hospital in Bangkok, Thailand: Five-Year Cross
Sectional Study.
AB - Background: Universal coverage (UC) scheme covers most of the population in
Thailand (76.3%) and diabetes (DM) was the most prevalent ambulatory disease in
most health care centers. Rajavithi Hospital is designated as one of the top
referral hospital in Bangkok. Objective: To examine the trend of avoidable
hospitalization related to diabetes in the UC patients who registered at
Rajavithi Hospital. Results: This cross-sectional study collected data from
electronic medical record from Rajavithi Hospital and the National Health
Security Office (NHSO). DM and related diseases based on a list of diagnosis
codes (ICD-10) were selected as an ambulatory care sensitive condition (ACSC) to
reflect the avoidable hospitalization. Outpatient and inpatient data between 2007
and 2011 were studied. The ACSC rate was calculated by number of hospitalizations
on DM and related conditions divided by number of the DM patients visited as
ambulatory care. Conclusion: The avoidable hospitalization for DM patients
registered at Rajavithi Hospital was stable during the five years of the study.
Future study on avoidable hospitalization should cover admissions to other
hospitals and DM related conditions. Further studies should investigate the
reasons of avoidable hospitalization.
PMID- 29949315
TI - The Development of Simple Screening Tool for Predict Risk of Falls in Thai
Community-Dwelling Elderly.
AB - Objective: To develop and examine the psychometric properties of the Three Times
Sit-to-Stand Test (TTSST) to evaluate its functional capacity and to predict the
risk of fall in community-dwelling elderly. Material and Method: Thirty-six
subjects aged older than 60 years, who experienced fall or non-fall, were tested
for their functional ability using the TTSST and the Five Times Sit-to-Stand Test
(FTSST). Results: The data demonstrated excellent reliability (ICCs = 0.943
0.991) and could clearly distinguish the ability of falling and non-falling
subjects. In addition, the TTSST showed significant correlation with the FTSST (r
= 0.942, p<0.001), and was an excellent fall indicator (sensitivity 88.89%,
specificity 100%, AUC = 0.92, 95% CI = 0.81-1.00). Conclusion: The TTSST is a
valid and reliable method for assessing fall risk factors of community-dwelling
elderly. We recommend a TTSST greater than 4.54 seconds as the optimal cut-off
score for reliable fall risk prediction for the elderly.
PMID- 29949316
TI - Treatment of Anastomosis Stricture after Bilateral Ileal Ureter Reconstruction by
Contralateral Retrograde Approach: Case Report.
AB - A 37-year old woman with locally advanced uterine cervical cancer post concurrent
chemoradiation, presented with an early anastomotic stricture after ileal ureter
replacement due to the ischemic process during the reconstruction procedure. A
bilateral ureteral stent was considered in order to relieve the obstructive
uropathy. Multiple attempts were made to cannulate the stricture point between
the right renal pelvis and ileal ureter, although all of them failed. The
percutaneous contralateral nephrostomy tract was accessed and successfully used
to perform retrograde approach cannulation. Balloon dilation at the stricture
point and ureteral stent placement were successfully performed without any
complications. Therefore, the contralateral retrograde approach for ureteral
stent placement during bilateral ileal ureter reconstruction has been
demonstrated to be both feasible and safe.
PMID- 29949317
TI - Expression of airway mucus-associated proteins in rats with chronic obstructive
pulmonary disease with a cold-dryness symptom pattern.
AB - OBJECTIVE: To reveal the effects on expression of airway mucus-associated
proteins in rats withchronic obstructive pulmonary disease (COPD) and a cold
dryness symptom pattern induced by elastaseand smoking. METHODS: The COPD model
was established with an elastase dose into the trachea combined withexposure to
smoking; the COPD model cold-dryness symptom pattern was further developed
byexposure to a cold, dry environment. After 90 days, pathologic lung sections,
inflammatory cytokinelevels (measured by enzyme linked immunosorbent assay), mRNA
and protein expression of mucus-associated proteins and aquaporins (measured by
real-time polymerase chain reaction and westernblots) were examined. RESULTS:
Cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor
alpha (TNF-alpha) inthe COPD and the cold-dryness symptom pattern COPD groups
were all significantly higher than incontrols (each P < 0.01). IL-6 and IL-8
levels were higher in the cold-dryness symptom pattern COPDgroup than in the COPD
group (each P < 0.05). The AQP5 mRNA expression in the cold-dryness
symptompattern COPD and COPD groups was lower than in the control group (P <
0.01), and that in thecold-dryness symptom pattern COPD group was lower than the
COPD group (P < 0.05). The expressionof MUC5AC and MUC5B mRNAs in the cold
dryness symptom pattern COPD group andCOPD group was higher than in the control
group (each P < 0.01), and that in the cold-dryness symptompattern COPD group was
higher than the COPD group (P < 0.01, and P < 0.05, respectively).The ratio of
MUC5AC mRNA/MUC5B mRNA was COPD group < the cold-dryness symptom patternCOPD
group < the control group. AQP4 and AQP5 protein expression in the cold-dryness
symptompattern COPD group was lower than that in the COPD group which was lower
again than in thecontrol group. MUC5AC and MUC5B expression in the cold-dryness
symptom pattern COPD groupwas higher than in the COPD group and higher again than
in the control group. CONCLUSION: Cold-dryness affects the expression of mucus
associated protein mRNA and its corresponding proteins, reducing the secretion of
aquaporins and increasing the secretion of mucins. Imbalancein aquaporins and
mucins can affect the function of mucus, increasing airway obstruction.
PMID- 29949318
TI - Puerarin, an isoflavone compound extracted from Gegen (Radix Puerariae Lobatae),
modulates sclera remodeling caused by extremelylow frequency electromagnetic
fields.
AB - OBJECTIVE: To evaluate the protective effect of puerarin [an isoflavone compound
extracted from Gegen(Radix Puerariae Lobatae)] in scleral remodeling induced by
extremely low frequency electromagneticfields (ELF-EMFs). METHODS: Human fetal
scleral fibroblasts (HFSFs) were divided into 5 groups: (a) untreated
controls;(b) cells treated with ELF-EMFs; (c) cells treated with ELF-EMFs and
puerarin 0.1 MUM; (d) cells treatedwith ELF-EMFs and puerarin 1 MUM; (e) cells
treated with ELF-EMFs and puerarin 10 MUM. Cell proliferationactivity was
measured by the cell-counting kit-8 assay. Matrix metalloproteinase-2 (MMP-2)
activitywas measured by gelatin enzymography. MMP-2 and collagenI(COL1A1) mRNA,
protein expressionwere measured by Real-Time polymerase chain reaction , Western
blot analysis, respectively. RESULTS: Puerarin reduced the inhibition in cell
proliferation, MMP-2 activity, mRNA, protein expressionof HFSFs exposed to ELF
EMFs and enhanced the COL1A1 mRNA and protein expression. CONCLUSION: Puerarin
was found to participate in the matrix remodeling process. It might be a
potentialagent for the treatment of extracellular matrix degradation of sclera
associated with ocularconditions.
PMID- 29949319
TI - Optimization of dosage ratio of chlorogenic acid and gardenia glycosides in the
treatment of rats with fatty liver disease induced byhigh-fat feed.
AB - OBJECTIVE: To investigate the optimal dosage ratio of chlorogenic acid and
gardenia glycosides intreating the rates with fatty liver disease induced by high
fat feed. METHODS: A rat model of non-alcoholic fatty liver disease (NAFLD) was
established by using ahigh-fat diet. According to mathematical model "uniform
design", varying doses of chlorogenic acidand gardenia glycosides have been
combined to form 6 medications for the treatment of NAFLD.Samples were then taken
to observe pathological changes of the liver tissue (HE staining); changes inthe
fat metabolism pathway e.g. triglyceride (TG) and free fatty acid (FFA) content;
alterations in liverfunction, i.e. serum alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) activity; anddifferences in Malondialdehyde
(MDA) and superoxide dismutase (SOD) content in the liver tissue.
Multipleregression analysis was conducted to test the optimal dosage ratio of
chlorogenic acid and gardeniaglycosides. RESULTS: Fatty degeneration and vacuole
like changes of different degrees occurred in hepaticcells of the model group.
Markers for fat metabolism, serum ALT and AST activities, and expressionof MDA in
liver tissue significantly increased, while SOD decreased. Combination of 90 mg
chlorogenicacid and 90 mg Gardenia glycosides was the optimal dosage ratio of
chlorogenic acid and gardeniaglycosides in the treatment of rats with fatty liver
induced by high-fat diet. CONCLUSION: Chlorogenic acid of 90 mg plus gardenia
glycosides of 90 mg was the best combinationin the treatment of fatty liver
disease in rats induced by high-fat feed.
PMID- 29949320
TI - Ethnopharmacological evaluation and antioxidant activity of some important herbs
used in traditional medicines.
AB - OBJECTIVE: To document the indigenous knowledge and evaluate the antioxidant
activity of medicinalherbs used for treatment of various diseases. METHODS: The
ethnomedicinal data were collected through semi-structured interviews of local
informantsalong with collection of herbarium specimens. The antioxidant activity
was evaluated by using1-diphenyl-2-picryl-hydrazyl radical scavenging assay.
RESULTS: A total of 12 important medicinal herbs were evaluated for
ethnomedicinal uses and antioxidantactivity. Medicinal plant diversity showed
that Solanaceae was the dominating family (3 spp.),followed by Asteraceae and
Lamiaceae (both 2 spp.). Leaves (31% ) were most frequently used inpreparation of
traditional medicines, and the most recommended mode of preparation was
powder(28% ). The antioxidant results revealed that the highest activity was
found in Atropa acuminataand Crocus sativus. CONCLUSION: The results of this
study proved that A. accuminata and C. sativus can be the excellentsources of
antioxidant compounds. A sustainable use and conservation of the valuable natural
resourcegreatly promote the development of functional food additives and
cosmetics.
PMID- 29949321
TI - Toxic effect of Tropaeolum majus L. leaves on spermatogenesis in mice.
AB - OBJECTIVE: To evaluate the hydroethanolic extract toxicity, obtained from
Tropaeolum majus L. (TM) on mouse testicular tissue. METHOD: In this experimental
study, we used 32 male NMRI mice. The experimental groups received 75, 375 and
750 mg/kg of TM extract, respectively. Twenty-four hours after the last
experimental day, serum samples were collected for hormonal measurement. Then,
the cauda of epididymis and testis were removed for sperm count and
histopathological assessments. RESULTS : Testosterone serum and testicular levels
decreased in 750 mg/kg in the treated group when compared to the control animals
(1.65+/-0.25; p=0.041 and 98.83+/-8.67; p=0.034 respectively). Histopathological
criteria such as epithelial vacuolization (9.3+/-1.1; p=0.034), sloughing (4.3+/
0.4; p=0.027) and detachment (12.2+/-0.9; p=0.031) of germ cells were
significantly increased in 750 mg/kg in the treated mice. In addition, there were
no significant changes in histopathological criteria; sperm head numbers,
Johnsen's scoring, and morphometry assessments were carried out in the 75 and 375
mg/kg treated mice. At the dose of 750 mg/kg, the seminiferous tubule diameter
(193.2+/-4.6; p=0.019), seminiferous epithelium height (139.2+/-5.1; p=0.023),
and maturation arrest were significantly decreased in this group. CONCLUSION : In
conclusion, TM extract has toxic effects on the mouse testicular tissue in high
doses. Hence, we recommend caution concerning its consumption by patients with
reproductive problems.
PMID- 29949322
TI - Are age and anti-Mullerian hormone good predictors of ovarian reserve and
response in women undergoing IVF?
AB - OBJECTIVE: Ovarian reserve evaluation has been the focus of substantial clinical
research for several years. This study aimed to examine the associations between
markers of ovarian reserve and ovarian response. METHODS: This prospective study
included 132 infertile women aged 24-48 years undergoing routine exploration
during unstimulated cycles prior to the start of assisted reproductive technology
(ART) treatments at our center from July 2015 to January 2017. Descriptive
parameters and patient characteristics were reported as mean (SD) or median
(range) values depending on the data distribution pattern. Student's t-test was
performed for continuous variables; the Wilcoxon and Pearson's test were used for
data not following a normal distribution; and Fisher's test was used for
categorical variables. p<0.05 was considered statistically significant. RESULTS:
At the time of the study, the patients had a mean age of 35.7+/-3.84 years. On
day 3 of the cycle, the mean anti-Mullerian hormone (AMH) serum level was 2.84+/
1.57 ng/mL and the patients had 14.68+/-4.2 antral follicles (AFC). A significant
correlation was observed between AMH and age (r=-0.34 p<.01), follicle
stimulating hormone (FSH) serum levels (r=-0.32, p<.01), AFC (r=0.81, p<.00001),
total dose of medication during ovarian stimulation (r=-0.28, p<.0003), and
ongoing pregnancy rate (p<.05). Age was significantly correlated with FSH
(r=0.46, p<.01), AFC (r=-0.34, p<.00001), total dose of medication during ovarian
stimulation (r=0.43, p<.0003), and ongoing pregnancy rate (p<.04). CONCLUSION :
Serum AMH and age are independent predictors of ovarian reserve and ovarian
stimulation outcome in infertile women. Age and serum AMH level may be used to
advise subfertile couples of their pregnancy prospects.
PMID- 29949323
TI - Reproductive outcomes of vitrified blastocyst transfer in modified natural cycle
versus mild hormonally stimulated and artificial protocols: A randomized control
trial.
AB - OBJECTIVE: This study set out to investigate the pregnancy outcome of natural
cycle regimen versus other endometrial preparation protocols with vitrification
thawed blastocyst transfer (VTBT) cycles. METHODS: This control trial study was
carried out on 123 women undergoing VTBT. The women were randomly divided into
three groups of endometrial preparation before VTBT; 1. Modified natural
ovulation cycle with using HCG (n=32) 2. Mild hormonally stimulated cycle by low
dose Clomiphene Citrate (n=30) and 3. Artificial cycle induced with estradiol and
progesterone supplementation (n=61). Following endometrial preparation, the
thawed blastocyst was vitrified and transferred. Reproductive outcome and
endometrium characteristic were evaluated in the three groups. RESULTS: The three
above-mentioned protocols resulted in clinical pregnancy rates of 21.43% vs.
13.79% vs. 15.25%, respectively; without statistical differences. The ongoing
pregnancy rates did not show any significant differences among the three groups
(21.43% vs. 13.79% vs. 13.56%), respectively. In addition, the miscarriage rates
were compared in the three groups. The endometrial thickness on the day of
progesterone or human chorionic gonadotropin administration were more frequently
observed in the artificial and modified natural cycle versus hormonally
stimulated groups (8.34+/-0.89 vs. 7.3+/-1.4, p<0.001; 8.13+/-0.95 vs. 7.3+/-1.4,
p<0.001). There was no significant difference regarding triple-line endometrial
patterns in the three groups. CONCLUSION: The natural cycle with HCG trigger
could be considered as an alternative protocol to mild hormonally or artificial
cycle regimens in vitrification thawed blastocyst transfers.
PMID- 29949328
TI - Safety and efficacy of Tongkuaixiao ointment in reliving cancer-induced pain: a
multicenter double-blind placebo-controlled randomizedtrial.
AB - OBJECTIVE: To evaluate the safety and efficacy of Tongkuaixiao ointment (TKXO) in
treating moderate-to-severe cancer induced somatalgia. METHODS: Totally 130
patients with moderateto-severe cancer induced somatalgia were randomlydivided
into a TKXO group and a control group. The patients were treated with either TKXO
appliedexternally or placebo, with opioid analgesics orally at the same time.
Observation parameterswere included numerical rating scale (NRS) scores,
analgesic efficacy, initiation effective time, persistentanalgesic time,
equivalent morphine dose, National Comprehensive Cancer Network (NCCN)grade in
Impact of Pain Measurement Scores, and safety and satisfaction extent
investigation. RESULTS: NRS scores and NCCN grade in Impact of Pain Measurement
Scores decreased significantlyafter 5-days' treatment in the two groups (P <
0.0001). Compared to the control group, initiationeffective time was
significantly shorter (P < 0.05) and persistent analgesic time was significantly
longer(P < 0.01), equivalent oral morphine doses of the first day and the whole
treatment course weresignificantly decreased in the TKXO treatment group (P <
0.01 or P < 0.05). No obvious adverse effectswere found in the TKXO group.
CONCLUSION: TKXO combined with opioid analgesics possesses the advantages of high
efficacy,fast action, long persistent action, safety and convenience in use, and
it can reduce the dose ofopioid.
PMID- 29949329
TI - Effect of Rorrico, extracted from group of Chinese medicines, on influenza A and
H1N1 infections.
AB - OBJECTIVE: To investigate the therapeutic and preventive effects of Rorrico on
influenza, especially influenzaA viral infection, including swine flu (H1N1) in
humans. METHODS: Eighty-nine subjects were recruited in Hong Kong and Macau, and
divided into treatmentgroup (TG) and prevention group (PG) based on their
influenza A and swine flu symptoms. All subjectswere prescribed Rorrico or
placebo, and monitored by a Chinese medicine practitioner. Bloodsamples were
collected before and after 7-day Rorrico or placebo treatment for laboratory
investigations. RESULTS: After treatment, there were some full recoveries and
obvious relief of onset symptoms inthe TG. Blood test results showed that Rorrico
produced (a) no adverse effects on subjects' renal and liver functions, muscle
enzyme and hematological status, (b) no up-regulation of pro-inflammatory
cytokinestumour necrosis factor-a and interleukin-18 in both TG and PG, (c) mild
yet statistically significantelevation of plasma mannose-binding lectin (MBL) in
PG. CONCLUSION: Rorrico has no up-regulating effect on the participants' immune
response, or, equallylikely, the immuno-modulatory effects of Rorrico do not non
specifically or unnecessarily promoteinflammation when not required. It is
possible that oral administration of Rorrico can promote hepaticsynthesis of MBL
in healthy PG subjects, thereby conferring increased protection against
infection.
PMID- 29949330
TI - Protective effect of Xuebijing injection on myocardial injury in patients with
sepsis: a randomized clinical trial.
AB - OBJECTIVE: To investigate the protective effect and possible mechanism of
Xuebijing Injection onmyocardial injury in patients with sepsis, and to evaluate
its prognostic implications. METHODS: Patients with septic myocardial injury were
recruited, and were randomly divided intotwo groups: treatment group and control
group. All patients in two groups received conventional clustertreatment, the
patients in treatment group additional received Xuebijing injection dissolved
in0.9% sodium chloride injection, and the patients in control group received the
same amount of 0.9%sodium chloride injection. At the beginning of treatment and
3, 7 and 10-day after treatment, laboratory indicators of cardiac troponin I
(cTnI), N-terminal proB-type natriuretic peptide (NT-proBNP)and procalcitonin
(PCT) were respectively tested in venous blood. The patient's length of stay
inIntensive Care Unit (ICU) and the mortality in 28 days were recorded. RESULTS:
At 3, 7 and 10-day after treatment, the improvements of cTnI, NT-proBNP and PCT
in treatmentgroup were better than those in control group, and the differences
were statistically significant(P < 0.05). The mortality of treatment group in 28
days was not significantly different from that ofcontrol group (P > 0.05). The
ICU length of stay of treatment group was shorter than that of controlgroup (P >
0.05). CONCLUSION: Xuebijing injection could improve the levels of cTnI, NT
proBNP and PCT in patientswith septic myocardial injury .and it had a protective
effect on myocardial injury.
PMID- 29949331
TI - Immediate analgesic effect of needling acupoints (bilateral De Qi vs unilateral
De Qi) on primary dysmenorrhea: a multi-center, randomized,controlled trail.
AB - OBJECTIVE: To analyze the effect of needling acupoints (bilateral vs unilateral)
with De Qi using datacollected from 501 primary dysmenorrhea (PD) patients
participating in multi-center, randomized,controlled trail. METHODS: De Qi was
defined as at least one of the feelings in soreness, numbness, fullness or
heavinessat the acupoints when stimulated with needles. The 501 patients were
grouped in 3 groups interms of De Qi or not De Qi in one side (unilateral) or
both sides (bilateral) of the body: bilateral De Qigroup, unilateral De Qi group,
and non-De Qi group. The abdominal pains were measured usingvisual analog scale
(VAS). RESULTS: In 501 patients, 472 acquired De Qi at unilateral acupoints, 24
De Qi at bilateral acupoint,and 5 had no De Qi at any acupoint. The data of non
De Qi group was excluded as the sample wasless than 5% of that in the bilateral
De Qi group. There was significant difference in the VAS beforeand after
treatment between unilateral and bilateral De Qi group (P < 0.01). After
stratified by acupoints,for the patients needled at Sanyinjiao (SP 6) and
Xuanzhong (GB 39), VAS scores in the bilateralDe Qi group were larger than those
in the unilateral De Qi group (P < 0.05). CONCLUSION: Bilateral De Qi was
possibly superior to unilateral De Qi in enhancing the immediateanalgesic effect
of needling the acupoints, but no statistical significance was observed on the
patients of needling at non acupoint, which preliminarily suggested this
immediate analgesic effect was perhaps along meridians.
PMID- 29949332
TI - Clinical effect of traditional Chinese spinal orthopedic manipulation in
treatment of chondromalacia patellae.
AB - OBJECTIVE: To evaluate the clinical effect of traditional Chinese spinal
orthopedic manipulation (TCSOM)in treating chondromalacia patellae (CP). METHODS:
Sixty cases of CP patients were randomly assigned to a TCSOM group and a
Celecoxibgroup according to the random number table method. All patients in the
TCSOM group weretreated with a maximum of 10 spinal manipulations and
rehabilitation training of quadriceps femoris.The symptoms before and after
treatment were assessed with visual analog scale (VAS) andKujala functional knee
scoring system (KFKSS). A symptom improvement rate (SIR) was implementedin order
to evaluate the effects of the treatments. RESULTS: The symptoms of 16 patients
in the TCSOM group quickly resolved after the first spinalmanipulation and 8
cases were significantly improved. The VAS scores in the TCSOM group after 4weeks
of treatment were significantly lower than those in the Celecoxib group. The
KFKSS scores inthe TCSOM group after 4 weeks of treatment were significantly
higher than those in the Celecoxibgroup. Side effects of the treatment were not
reported. Symptom improvement rate based on theVAS in the TCSOM group indicated
more significant improvements than the Celecoxib group. CONCLUSION: TCSOM has
greater efficacy than Celecoxib capsules for relief of the symptoms of CP.
PMID- 29949333
TI - The effects of tumor necrosis factor-alpha (TNF-alpha) and IL-1 receptor
antagonist (IL-1Ra) polymorphisms on recurrent abortion in Azari women.
AB - Objectives: Recurrent pregnancy loss (RPL) is a heterogeneous condition
consisting of three or more consecutive abortions before the 20 weeks of
gestation. The tumor necrosis factor alpha (TNF-alpha) gene plays a crucial role
in immunology and inflammation responses. Interleukin 1 receptor antagonist (IL
1RN) is an important anti-inflammatory molecule which plays important roles in
pregnancy. The aim of this study was to investigate effects of TNF-alpha and IL
1Ra polymorphisms on RPL in Azari women. Material and Methods: The study
participants consisted of 100 women with RPL from Iranian Azeri Turkish origin.
The control group comprised 100 age and ethnically matched healthy women in the
reproductive age. Genomic DNA wasextracted from the whole blood and genotype
determinations were performed using PCR amplification followed by restriction
fragment length polymorphism (RFLP) analysis. Results: No significant association
was indicated between IL-1Ra and RPL among Iranian Azeri Turkish women. Unlike
the homozygous state, significantly higher frequency of -857 C/T variant was seen
in RPL patients than control subjects. Significantly lower frequency of wild type
genotype was observed in RPL patients than of controls. Any association was found
between the other TNF-alpha polymorphisms and RPL. Conclusions: TNF-alpha -857
C/C variant might represent protective effect against RPL and the -857 C/T
variant might be a genetic risk factor for the occurrence of RPL. Invariant
differences in the prevalence of -511 C/T and -31 C/T polymorphisms and IL-1RN
VNTR between RPL patients.
PMID- 29949334
TI - A manual acupuncture treatment attenuates common cold and its symptoms: a case
series report from South Korea.
AB - OBJECTIVE: To investigate beneficial effects of manual acupuncture on common cold
periods andits symptoms depended on the difference onset time of common cold,
within 36 h or over thanthat. To prove effects of manual acupuncture on common
cold, a retrospective chart review was conducted. METHODS: Chart data for
patients with common cold who were treated with only manualacupuncture with
fulfilling Jackson scales and satisfaction at the end of each treatment
werecollected via multi-centers of Oriental hospitals, Oriental medicine clinics
and covalent hospital inSouth Korea. Totally 187 patients were divided into two
groups, Group I (115 patients, within 36 h)and Group II (72 patients, onset time
of cold over than 36 h). Finally 120 patients were observed untilentire
resolution of cold symptoms. RESULTS: Group I showed significant decreases
themediandurationsofcompletelyrecovery (3 days;95% CI 3.0-4.0) as compared with
Group II (6 days; 95% CI 4.0-7.0, P < 0.001). The manual acupuncturebeneficially
worked for reduction rate of common cold symptoms by 50% after initial
treatment,decreased cold symptoms, and reduced cold duration. CONCLUSION: Manual
acupuncture beneficially affected common cold and its symptoms.Moreover it is
more susceptibility on the early time of onset cold.
PMID- 29949335
TI - Effect of sodium houttuyfonate on symptom pattern of lung-Qi deficiency in rats
induced by bacterialbiofilm infection.
AB - OBJECTIVE: To investigate the in vivo inhibitory effects of sodium houttuyfonate
(SH) on symptompattern of Qi-deficiency in rats induced by infection of bacterial
biofilm on rat respiratory tract. METHODS: Symptom pattern is a term used in
Traditional Chinese Medicine (TCM) to define a clusterof symptoms in a medical
condition. Based on the pattern, TCM therapies are administered. The
symptompattern used in this study was lung-Qi deficiency pattern identified in
rats, which was induced bynasal intubation drip of Pseudomonas aeruginosa (P.
aeruginosa) (two strains) to form bacterial biofilmon airway combined with
stimulation of cold and fatigue. We measured the variations of thesymptoms of the
pattern, weight, spleen and thymus index, blood gas, lung bronchial tissue
pathologyand cytokine of rat in different treatments and control groups. RESULTS:
The rats of SH-treatment groups had not showed typical symptoms comparing with
modelgroup in the early stage of infection. The weight, spleen and thymus index
of the SH-treatmentgroups were significantly higher comparing with untreated
model group. The SH-treatment groupsalso showed higher O(2) partial pressure and
lower CO(2) partial pressure than model group. Furthermore,we found that the
bronchopulmonary section of SH-treatment groups not showed typical pathogenic
variation in model group. The comparison of cytokine concentration in different
groups indicated that SH could prevent the over-production of cytokine to reduce
the inflammation occurrence. CONCLUSION: In the early stage of airway infection
by biofilm of P. aeruginosa, application of SHcan prevent the occurrence of lung
Qi deficiency pattern.
PMID- 29949336
TI - Association of serum and follicular fluid leptin and ghrelin levels with in vitro
fertilization success.
AB - Objectives: The aim of this study was to evaluate the relationship between in
vitro fertilization (IVF) cycle outcomes, serum and follicular fluid (FF) levels
of leptin and ghrelin. Material and methods: Forty-four women who underwent
intracytoplasmic sperm injection cycles (ICSI) were enrolledin the study. On the
third day (D3) of the menstrual cycle, venous blood samples were drawn for serum
measurements of leptin and ghrelin. The follicular fluid (FF) and the
corresponding oocyte were obtained from a single dominant preovulatory follicle
at the time of oocyte pick-up. The FF and D3 serum leptin and ghrelin
concentrations were measured by enzyme-linked immunosorbent assay. The
relationship between pregnancy rate and serum, follicular fluid levels of leptin
and ghrelin were analyzed. Results: Of the 44 cases included, nineteen achieved
clinical pregnancy (43.18%). Follicular fluid ghrelin levels were significantly
lower in the pregnant group than non-pregnant group (p < 0.05) With respect to FF
leptin, there was no statistically significant differences between the pregnant
and non-pregnant women (p > 0.05). There was no statistically significant
difference in D3 serum ghrelin between pregnant and non-pregnant groups (p >
0.05). However, D3 serum leptin levels were significantly lower in pregnant women
than non-pregnant women (p < 0.05). Conclusions: Lower ghrelin levels in the
follicular fluid were associated with higher pregnancy rates. Also, D3 serum
leptinlevels were inversely correlated with clinical pregnancy rates. These
findings support the potential role of these molecules on IVF outcomes.
PMID- 29949337
TI - Rational Design of the Polymeric Amines in Solid Adsorbents for Postcombustion
Carbon Dioxide Capture.
AB - Substantial efforts have been made to increase the CO2 working capacity of amine
adsorbents for an efficient CO2 capture. However, the more important metric for
assessing adsorbents is the regeneration heat required for capturing a fixed
amount of CO2. In this work, we synthesized polyethyleneimine (PEI)/SiO2
adsorbents functionalized with various epoxides. This provided adsorbents with
six different amine structures showing various CO2/H2O adsorption properties. Our
studies revealed that the CO2 working capacity was not a decisive factor in
determining the regeneration heat required for CO2 capture. This is because the
benefit of large CO2 working capacity was canceled out by the difficulty of CO2
desorption. Instead, the suppression of H2O co-adsorption was critical for
reducing the regeneration heat because substantial latent heat is required for
H2O desorption. Consequently, the PEI/SiO2 functionalized with 1,2-epoxybutane
required a much lower regeneration heat (2.66 GJ tCO2-1) than the conventional
PEI/SiO2 (4.03 GJ tCO2-1) because of suppressed H2O co-adsorption as well as
moderately high CO2 working capacity.
PMID- 29949338
TI - Directed Flow of Micromotors through Alignment Interactions with Micropatterned
Ratchets.
AB - To achieve control over naturally diffusive, out-of-equilibrium systems composed
of self-propelled particles, such as cells or self-phoretic colloids, is a long
standing challenge in active matter physics. The inherently random motion of
these active particles can be rectified in the presence of local and periodic
asymmetric cues given that a nontrivial interaction exists between the self
propelled particle and the cues. Here, we exploit the phoretic and hydrodynamic
interactions of synthetic micromotors with local topographical features to break
the time-reversal symmetry of particle trajectories and to direct a macroscopic
flow of micromotors. We show that the orientational alignment induced on the
micromotors by the topographical features, together with their geometrical
asymmetry, is crucial in generating directional particle flow. We also show that
our system can be used to concentrate micromotors in confined spaces and identify
the interactions leading to this effect. Finally, we develop a minimal model,
which identifies the key parameters of the system responsible for the observed
rectification. Overall, our system allows for robust control over both temporal
and spatial distribution of synthetic micromotors.
PMID- 29949339
TI - Increasing the Resistance of Living Cells against Oxidative Stress by Nonnatural
Surfactants as Membrane Guards.
AB - The importation of construction principles or even constituents from biology into
materials science is a prevailing concept. Vice versa, the cellular level
modification of living systems with nonnatural components is much more difficult
to achieve. It has been done for analytical purposes, for example, imaging, to
learn something about intracellular processes. Cases describing the improvement
of a biological function by the integration of a nonnatural (nano)constituent are
extremely rare. Because biological membranes contain some kind of a surfactant,
for example, phospholipids, our idea is to modify cells with a newly synthesized
surfactant. However, this surfactant is intended to possess an additional
functionality, which is the reduction of oxidative stress. We report the
synthesis of a surfactant with Janus-type head group architecture, a fullerene
C60 modified by five alkyl chains on one side and an average of 20 oxygen species
on the other hemisphere. It is demonstrated that the amphiphilic properties of
the fullerenol surfactant are similar to that of lipids. Not only quenching of
reactive oxygen species (superoxide, hydroxyl radicals, peroxynitrite, and
hydrogen peroxide) was successful, but also the fullerenol surfactant exceeds
benchmark antioxidant agents such as quercetin. The surfactant was then brought
into contact with different cell types, and the viability even of delicate cells
such as human liver cells (HepG2) and human dopaminergic neurons (LUHMES) has
proven to be extraordinarily high. We could show further that the cells take up
the fullerenol surfactant, and as a consequence, they are protected much better
against oxidative stress.
PMID- 29949340
TI - Peroxidase versus Peroxygenase Activity: Substrate Substituent Effects as
Modulators of Enzyme Function in the Multifunctional Catalytic Globin
Dehaloperoxidase.
AB - The dehaloperoxidase-hemoglobin (DHP) from the terebellid polychaete Amphitrite
ornata is a multifunctional hemoprotein that catalyzes the oxidation of a wide
variety of substrates, including halo/nitrophenols, haloindoles, and pyrroles,
via peroxidase and/or peroxygenase mechanisms. To probe whether substrate
substituent effects can modulate enzyme activity in DHP, we investigated its
reactiviy against a panel of o-guaiacol substrates given their presence (from
native/halogenated and non-native/anthropogenic sources) in the benthic
environment that A. ornata inhabits. Using biochemical assays supported by
spectroscopic, spectrometric, and structural studies, DHP was found to catalyze
the H2O2-dependent oxidative dehalogenation of 4-haloguaiacols (F, Cl, and Br) to
2-methoxybenzoquinone (2-MeOBQ). 18O labeling studies confirmed that O atom
incorporation was derived exclusively from water, consistent with substrate
oxidation via a peroxidase-based mechanism. The 2-MeOBQ product further reduced
DHP to its oxyferrous state, providing a link between the substrate oxidation and
O2 carrier functions of DHP. Nonnative substrates resulted in polymerization of
the initial substrate with varying degrees of oxidation, with 2-MeOBQ identified
as a minor product. When viewed alongside the reactivity of previously studied
phenolic substrates, the results presented here show that simple substituent
effects can serve as functional switches between peroxidase and peroxygenase
activities in this multifunctional catalytic globin. More broadly, when recent
findings on DHP activity with nitrophenols and azoles are included, the results
presented here further demonstrate the breadth of heterocyclic compounds of
anthropogenic origin that can potentially disrupt marine hemoglobins or function
as environmental stressors, findings that may be important when assessing the
environmental impact of these pollutants (and their metabolites) on aquatic
systems.
PMID- 29949341
TI - Top-Down Characterization of Proteins with Intact Disulfide Bonds Using Activated
Ion Electron Transfer Dissociation.
AB - Here we report the fragmentation of disulfide linked intact proteins using
activated-ion electron transfer dissociation (AI-ETD) for top-down protein
characterization. This fragmentation method is then compared to the alternative
methods of beam-type collisional activation (HCD), electron transfer dissociation
(ETD), and electron transfer and higher-energy collision dissociation (EThcD). We
analyzed multiple precursor charge states of the protein standards bovine
insulin, alpha-lactalbumin, lysozyme, beta-lactoglobulin, and trypsin inhibitor.
In all cases, we found that AI-ETD provides a boost in protein sequence coverage
information and the generation of fragment ions from within regions enclosed by
disulfide bonds. AI-ETD shows the largest improvement over the other techniques
when analyzing highly disulfide linked and low charge density precursor ions.
This substantial improvement is attributed to the concurrent irradiation of the
gas phase ions while the electron-transfer reaction is taking place, mitigating
nondissociative electron transfer, helping unfold the gas phase protein during
the electron transfer event, and preventing disulfide bond reformation. We also
show that AI-ETD is able to yield comparable sequence coverage information when
disulfide bonds are left intact relative to proteins that have been reduced and
alkylated. This work demonstrates that AI-ETD is an effective fragmentation
method for the analysis of proteins with intact disulfide bonds, dramatically
enhancing sequence ion generation and total sequence coverage compared to HCD and
ETD.
PMID- 29949342
TI - Directional Porin Binding of Intrinsically Disordered Protein Sequences Promotes
Colicin Epitope Display in the Bacterial Periplasm.
AB - Protein bacteriocins are potent narrow spectrum antibiotics that exploit outer
membrane porins to kill bacteria by poorly understood mechanisms. Here, we
determine how colicins, bacteriocins specific for Escherichia coli, engage the
trimeric porin OmpF to initiate toxin entry. The N-terminal ~80 residues of the
nuclease colicin ColE9 are intrinsically unstructured and house two OmpF binding
sites (OBS1 and OBS2) that reside within the pores of OmpF and which flank an
epitope that binds periplasmic TolB. Using a combination of molecular dynamics
simulations, chemical trimerization, isothermal titration calorimetry,
fluorescence microscopy, and single channel recording planar lipid bilayer
measurements, we show that this arrangement is achieved by OBS2 binding from the
extracellular face of OmpF, while the interaction of OBS1 occurs from the
periplasmic face of OmpF. Our study shows how the narrow pores of oligomeric
porins are exploited by colicin disordered regions for direction-specific
binding, which ensures the constrained presentation of an activating signal
within the bacterial periplasm.
PMID- 29949343
TI - Surface Functionalization of Silicon, HOPG, and Graphite Electrodes: Toward an
Artificial Solid Electrolyte Interface.
AB - Electrografting of diazonium salts containing a protected alkyne moiety was used
for the first functionalization of silicon and highly ordered pyrolytic graphite
model surfaces. After deprotection with tetrabutylammonium fluoride, further
layers were added by the thiol-yne click chemistry. The composition of each layer
was characterized via X-ray photoelectron spectroscopy and time-of-flight
secondary ion mass spectrometry. The same approach was then used to functionalize
graphite powder electrodes, which are classically used as negative electrode in
lithium-ion batteries. The effect of the coating on the formation of the solid
electrolyte layer was investigated electrochemically by cyclovoltammetry and
galvanostatic measurements. The modified graphite electrodes showed different
reduction peaks in the first cycle, indicating reduced and altered decomposition
processes of the components. Most importantly, the electrochemical investigations
show a remarkable reduction of irreversible capacity loss of the battery.
PMID- 29949344
TI - Novel Nonconjugated Polymer as Cathode Buffer Layer for Efficient Organic Solar
Cells.
AB - A novel nonconjugated polymer named poly(2-acrylamido-2-methyl-1-propanesulfonic
acid sodium salt) (PAMPS-Na) was designed and synthesized. The PAMPS-Na has good
solubility in polar solvents, such as water, methanol, and ethanol, which can be
used as the cathode buffer layer in organic solar cells (OSCs) through solution
processing without damaging the underlying active layer. Moreover, it was found
that PAMPS-Na can significantly decrease the Al work function when it was
modified with Al. To reveal its universal application in organic photovoltaic
devices, a variety of photovoltaic donor materials, including two medium-band gap
polymers, a wide-band gap polymer, and a small molecule donor were employed to
fabricate OSCs. Compared with OSCs with Ca/Al electrode, the devices based on
PAMPS-Na/Al exhibited higher photovoltaic performance, mainly because of the
increased short-circuit current. Additionally, OSCs with PAMPS-Na/Al displayed
better ambient stability than devices with Ca/Al. It is also interesting to find
that the performance of the devices can tolerate a wide change of PAMPS-Na's
thickness, enabling the potential for large-scale fabrication of OSCs. The
results suggest that PAMPS-Na is a promising candidate as the cathode buffer
layer to improve the efficiency and stability of OSCs.
PMID- 29949345
TI - Fabrication and Microscopic and Spectroscopic Characterization of Cytocompatible
Self-Assembling Antimicrobial Nanofibers.
AB - The discovery of antimicrobial peptides (AMPs) has brought tremendous promise and
opportunities to overcome the prevalence of bacterial resistance to commonly used
antibiotics. However, their widespread use and translation into clinical
application is hampered by the moderate to severe hemolytic activity and
cytotoxicity. Here, we presented and validated a supramolecular platform for the
construction of hemo- and cytocompatible AMP-based nanomaterials, termed self
assembling antimicrobial nanofibers (SAANs). SAANs, the "nucleus" of our
antimicrobial therapeutic platform, are supramolecular assemblies of de novo
designed AMPs that undergo programmed self-assembly into nanostructured fibers to
"punch holes" in the bacterial membrane, thus killing the bacterial pathogen. In
this study, we performed solid-state NMR spectroscopy showing predominant
antiparallel beta-sheet assemblies rather than monomers to interact with
liposomes. We investigated the mode of antimicrobial action of SAANs using
transmission electron microscopy and provided compelling microscopic evidence
that self-assembled nanofibers were physically in contact with bacterial cells
causing local membrane deformation and rupture. While effectively killing
bacteria, SAANs, owing to their nanoparticulate nature, were found to cross
mammalian cell membranes harmlessly with greatly reduced membrane accumulation
and possess exceptional cytocompatibility and hemocompatibility compared to
natural AMPs. Through these systematic investigations, we expect to establish
this new paradigm for the customized design of SAANs that will provide exquisite,
tunable control of both bactericidal activity and cytocompatibility and can
potentially overcome the drawbacks of traditional AMPs.
PMID- 29949346
TI - Naturally Occurring Disease-Related Mutations in the 40-57 Omega-Loop of Human
Cytochrome c Control Triggering of the Alkaline Isomerization.
AB - Naturally occurring mutations found in one of the two Omega-loop substructures in
human cytochrome c are associated with low blood platelet count
(thrombocytopenia). Both Omega-loops participate in the formation of conformers
associated with cytochrome c peroxidase activity and apoptotic function. At
alkaline pH values, the Met80 ligand to the ferric heme iron dissociates, and a
lysine residue in the 71-85 Omega-loop coordinates to the iron. The alkaline
isomerization has been the focus of extensive kinetic studies, and it is
established that a deprotonation triggers the release of the Met80 ligand (p
Ktrigger). A second deprotonation stabilizes a pentacoordinate heme form (p Ka2).
In this study, site-directed variants at the 41 and 48 positions in the 40-57
Omega-loop and at the 81 and 83 positions in the 71-85 Omega-loop reveal that
conformational transitions in the 71-85 Omega-loop, leading to the alkaline or
peroxidatic conformers, are controlled by the 40-57 Omega-loop. We find that the
variants causing thrombocytopenia, G41S and Y48H, lower the p Ktrigger and
increase p Ka2. Our results are presented in a mechanistic framework, depicted by
a cube, that accounts for the pH dependencies of the equilibrium and kinetic
parameters governing the alkaline transition of the native protein and Omega-loop
variants. The data are most consistent with the trigger for Met80 replacement by
a lysine being a deprotonation within a hydrogen bonded unit that links the two
Omega-loops rather than an individual group. Such a proposal aligns with the
entatic contribution made by the same unit in controlling the Met80-Fe(III) bond
strength.
PMID- 29949347
TI - "Tag and Modify" Protein Conjugation with Dynamic Covalent Chemistry.
AB - The development of small protein tags that exhibit bioorthogonality, bond
stability, and reversibility, as well as biocompatibility, holds great promise
for applications in cellular environments enabling controlled drug delivery or
for the construction of dynamic protein complexes in biological environments.
Herein, we report the first application of dynamic covalent chemistry both for
purification and for reversible assembly of protein conjugates using interactions
of boronic acid with diols and salicylhydroxamates. Incorporation of the boronic
acid (BA) tag was performed in a site-selective fashion by applying disulfide
rebridging strategy. As an example, a model protein enzyme (lysozyme) was
modified with the BA tag and purified using carbohydrate-based column
chromatography. Subsequent dynamic covalent "click-like" bioconjugation with a
salicylhydroxamate modified fluorescent dye (BODIPY FL) was accomplished while
retaining its original enzymatic activity.
PMID- 29949348
TI - Nanoparticle-Assisted Transcutaneous Delivery of a Signal Transducer and
Activator of Transcription 3-Inhibiting Peptide Ameliorates Psoriasis-like Skin
Inflammation.
AB - Signal transducer and activator of transcription 3 (STAT3) is constitutively
activated in psoriatic skin inflammation and acts as a key player in the
pathogenesis and progression of this autoimmune disease. Although numerous
inhibitors that intervene in STAT3-associated pathways have been tested, an
effective, highly specific inhibitor of STAT3 has yet to be identified. Here, we
evaluated the in vitro and in vivo biological activity and therapeutic efficacy
of a high-affinity peptide specific for STAT3 (APTstat3) after topical treatment
via intradermal and transcutaneous delivery. Using a preclinical model of
psoriasis, we show that intradermal injection of APTstat3 tagged with a 9
arginine cell-penetrating peptide (APTstat3-9R) reduced disease progression and
modulated psoriasis-related cytokine signaling through inhibition of STAT3
phosphorylation. Furthermore, by complexing APTstat3-9R with specific lipid
formulations led to formation of discoidal lipid nanoparticles (DLNPs), we were
able to achieve efficient skin penetration of the STAT3-inhibiting peptide after
transcutaneous administration, thereby effectively inhibiting psoriatic skin
inflammation. Collectively, these findings suggest that DLNP-assisted
transcutaneous delivery of a STAT3-inhibiting peptide could be a promising
strategy for treating psoriatic skin inflammation without causing adverse
systemic events. Moreover, the DLNP system could be used for transdermal delivery
of other therapeutic peptides.
PMID- 29949349
TI - An Engineered Constitutive Promoter Set with Broad Activity Range for Cupriavidus
necator H16.
AB - Well-characterized promoters with variable strength form the foundation of
heterologous pathway optimization. It is also a key element that bolsters the
success of microbial engineering and facilitates the development of biological
tools like biosensors. In comparison to microbial hosts such as Escherichia coli
and Saccharomyces cerevisiae, the promoter repertoire of Cupriavidus necator H16
is highly limited. This limited number of characterized promoters poses a
significant challenge during the engineering of C. necator H16 for
biomanufacturing and biotechnological applications. In this article, we first
examined the architecture and genetic elements of the four most widely used
constitutive promoters of C. necator H16 (i.e., P phaC1, P rrsC, P j5, and P g25)
and established a narrow 6-fold difference in their promoter activities. Next,
using these four promoters as starting points and applying a range of genetic
modifications (including point mutation, length alteration, incorporation of
regulatory genetic element, promoter hybridization, and configuration
alteration), we created a library of 42 constitutive promoters, all of which are
functional in C. necator H16. Although these promoters are also functional in E.
coli, they show different promoter strength and hierarchical rank of promoter
activity. Subsequently, the activity of each promoter was individually
characterized, using l-arabinose-inducible P BAD promoter as a benchmark. This
study has extended the range of constitutive promoter activities to 137-fold,
with some promoter variants exceeding the l-arabinose-inducible range of P BAD
promoter. Not only has the work enhanced our flexibility in engineering C.
necator H16, it presented novel strategies in adjusting promoter activity in C.
necator H16 and highlighted similarities and differences in transcriptional
activity between this organism and E. coli.
PMID- 29949350
TI - Selective Three-Component Coupling for CO2 Chemical Fixation to Boron Guanidinato
Compounds.
AB - A selective three-component coupling was employed to fix carbon dioxide to boron
guanidinato compounds. The one-pot reaction of carbon dioxide, carbodiimides, and
borylamines (ArNH)BC8H14 afforded the corresponding 1,2-adducts
{R(H)N}C{N(Ar)}(NR)(CO2)BC8H14. Alternatively, the reaction with p-MeOC6H4NC or
2,6-Me2C6H3NC gave the corresponding isocyanide 1,1-adducts { i-PrHN}C{N(p-Me
C6H4)}(N i-Pr){CNAr}BC8H14. The molecular structures of products (2,6- i
Pr2C6H3NH)BC8H14 7, { i-Pr(H)N}C{N(p-MeC6H4)}(N i-Pr)(CO2)BC8H14 9, {Cy(H)N}C{N(
p-MeC6H4)}(Cy)(CO2)BC8H14 13, and { i-PrHN}C{N( p-MeC6H4)}(N i-Pr){CNR"}BC8H14
(R" = p-MeOC6H4, 2,6-Me2C6H3) 14 and 15 were established by X-ray diffraction.
Density functional theory calculations at the M05-2X level of theory revealed
that CO2 fixation and formation of the corresponding adduct is exothermic and
proceeds via a nonchelate boron guanidinato intermediate.
PMID- 29949351
TI - Rapid Screening Detection of Genetically Modified Crops by Loop-Mediated
Isothermal Amplification with a Lateral Flow Dipstick.
AB - We developed a novel loop-mediated isothermal amplification (LAMP)-based
detection method using lateral flow dipstick chromatography for genetically
modified (GM) soybean and maize events. The single-stranded tag hybridization
(STH) for the chromatography printed-array strip (C-PAS) system was used for
detections targeting the cauliflower mosaic virus 35S promoter, mannose-6
phosphate isomerase gene, Pisum sativum ribulose 1, 5-bisphosphate carboxylase
terminator, a common sequence between the Cry1Ab and Cry1Ac genes, and a GA21
specific sequence. The STH C-PAS system was applicable for multiplex analyses to
perform simultaneous detections. The limit of detection was 0.5% or less for each
target. By using the developed method, the LAMP amplification was visually
detected. Moreover, the detection could be carried out without any expensive
instruments, even for the DNA amplification steps, by virtue of the isothermal
reaction. We demonstrated that the rapid and useful method developed here would
be applicable for screening GM crops.
PMID- 29949352
TI - Mechanistic Understanding of Uranyl Ion Complexation on Montmorillonite Edges: A
Combined First-Principles Molecular Dynamics-Surface Complexation Modeling
Approach.
AB - Systematic first-principles molecular dynamics (FPMD) simulations were carried
out to study the structures, free energies, and acidity constants of UO22+
surface complexes on montmorillonite in order to elucidate the surface
complexation mechanisms of the uranyl ion (UO22+) on clay mineral edges at the
atomic scale. Four representative complexing sites were investigated, that is,
=Al(OH)2 and =AlOHSiO on the (010) surface and =AlOHOa and =SiOOa on the (110)
surface. The results show that uranyl ions form bidentate complexes on these
sites. All calculated binding free energies for these complexes are very similar.
These bidentate complexes can be hydrolyzed, and their corresponding derived p Ka
values (around 5.0 and 9.0 for p Ka1 and p Ka2, respectively) indicate that
UO2(OH)+ and UO2(OH)2 surface groups are the dominant surface species in the
environmental pH range. The OH groups of UO2(OH)2 surface complexes can act as
complexing sites for subsequent metals. Additional simulations showed that such
multinuclear adsorption is feasible and can be important at high pH. Furthermore,
FPMD simulation results served as input parameters for an electrostatic
thermodynamic surface complexation model (SCM) that adequately reproduced
adsorption data from the literature. Overall, this study provides an improved
understanding of UO22+ complexation on clay mineral edge surfaces.
PMID- 29949353
TI - Libertellenones O-S and Eutypellenones A and B, Pimarane Diterpene Derivatives
from the Arctic Fungus Eutypella sp. D-1.
AB - Seven new pimarane-type diterpene derivatives, libertellenones O-S (1-5) and
eutypellenones A and B (6 and 7), together with two known compounds (8 and 9),
were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude
soil of the Arctic. Their structures were elucidated from spectroscopic data, as
well as experimental and calculated electronic circular dichroism (ECD) analysis.
Structurally, compounds 1-5 possess a cyclopropyl-fused pimarane diterpene
moiety, whereas compounds 6 and 7 share an unusual cyclobutyl-fused pimarane
diterpene skeleton. Compounds 1-9 exhibited cytotoxicities against HeLa, MCF-7,
HCT-116, PANC-1, and SW1990 cells, with IC50 values in the range of 0.3 to 29.4
MUM. Compounds 6 and 7 could dose-dependently inhibit the activity of NF-kappaB
and exhibited significantly inhibitory effects on nitric oxide production induced
by lipopolysaccharide.
PMID- 29949354
TI - A Bioactive l-Phenylalanine-Derived Arene in Multitargeted Organoruthenium
Compounds: Impact on the Antiproliferative Activity and Mode of Action.
AB - RuII(eta6-arene) compounds carrying bioactive flavonol ligands have shown
promising anticancer activity against tumor cells via a multitargeting mode of
action, i.e., through interaction with DNA and inhibition of topoisomerase
IIalpha. By introducing a novel arene ligand based on the amino acid l
phenylalanine (Phe), we aimed to alter the pharmacological properties of the
complexes. We report here a series of novel RuII(eta6-arene)Cl complexes with
different substituents on the phenyl ring of the flavonol which should maintain
the multitargeting capability of the parent eta6- p-cymene (cym) complexes.
Studies with selected examples revealed stability in aqueous solution after
quickly forming aqua complexes but rapid decomposition in pure DMSO. The
reactions with protein and DNA models proceeded quickly and resulted in cleavage
of the flavonol or adduct formation, respectively. The compounds were found to be
cytotoxic with significant antiproliferative activity in cancer cells with IC50
values in the low MUM range, while not following the same trends as observed for
the cym analogues. Notably, the cellular accumulation of the new derivatives was
significantly higher than for their respective cym complexes, and they induced
DNA damage in a manner similar to that of cisplatin but to a lesser extent.
PMID- 29949355
TI - gamma-Bi2O3 - To Be or Not To Be? Comparison of the Sillenite gamma-Bi2O3 and
Isomorphous Sillenite-Type Bi12SiO20.
AB - The "controlled" synthesis of metastable gamma-Bi2O3 by solution based approaches
was reported several times recently, but the formation of Bi12SiO20 in the
presence of trace amounts of silicates renders the results to be questionable.
Here, the preparation of the Sillenite gamma-Bi2O3 and the Sillenite-type
Bi12SiO20 starting from the polynuclear bismuth oxido cluster
[Bi38O45(O2CC3H5)24(DMSO)9] is reported. gamma-Bi2O3 crystallizes after
calcination at 800 degrees C of the silicate-free hydrolysis product
"[Bi38O45(OH)24]" on a silver sheet. Corrosion of the substrate causes
contamination with silver, which is not incorporated into the Bi-O lattice, and
was removed by treatment with an aqueous KCN-solution. Bi12SiO20 was obtained
after hydrothermal treatment of the bismuth oxido cluster in the presence of NaOH
in glass vessels or Na2SiO3 in a Teflon-lined reactor vessel followed by
calcination at 600 degrees C. PXRD studies, scanning electron microscopy,
nitrogen adsorption measurements, IR- and Raman spectroscopy, diffuse UV-vis
spectroscopy, and DSC were used for characterization. The phase transition of
gamma-Bi2O3 to give alpha-Bi2O3 occurred slowly in the temperature range of 348
510 degrees C ( Delta Hgamma->alpha = 6.57 kJ.mol-1). The silver-containing
gamma-Bi2O3 exhibits slightly increased Raman modes compared to the silver-free
sample due to the SERS effect. In the diffuse UV-vis spectrum gamma-Bi2O3
exhibits an absorption edge at lambda = 485 nm ( E g = 2.76 eV), and the
contamination with silver results in an additional absorption edge at lambda =
572 nm. Silver-free gamma-Bi2O3 exhibits an absorption edge at lambda = 460 nm (
E g = 2.83 eV) and Bi12SiO20 at lambda = 422 nm ( E g = 3.16 eV). The
photocatalytic activity of the compounds was investigated in the decomposition of
aqueous rhodamine B under visible light irradiation, showing silver-containing
gamma-Bi2O3 to be slightly more effective compared to Bi12SiO20 and significantly
more effective than the silver-free gamma-Bi2O3.
PMID- 29949356
TI - Generalized Born Based Continuous Constant pH Molecular Dynamics in Amber:
Implementation, Benchmarking and Analysis.
AB - Solution pH plays an important role in structure and dynamics of biomolecular
systems; however, pH effects cannot be accurately accounted for in conventional
molecular dynamics simulations based on fixed protonation states. Continuous
constant pH molecular dynamics (CpHMD) based on the lambda-dynamics framework
calculates protonation states on the fly during dynamical simulation at a
specified pH condition. Here we report the CPU-based implementation of the CpHMD
method based on the GBNeck2 generalized Born (GB) implicit-solvent model in the
pmemd engine of the Amber molecular dynamics package. The performance of the
method was tested using pH replica-exchange titration simulations of Asp, Glu and
His side chains in 4 miniproteins and 7 enzymes with experimentally known p Ka's,
some of which are significantly shifted from the model values. The added
computational cost due to CpHMD titration ranges from 11 to 33% for the data set
and scales roughly linearly as the ratio between the titrable sites and number of
solute atoms. Comparison of the experimental and calculated p Ka's using 2 ns per
replica sampling yielded a mean unsigned error of 0.70, a root-mean-squared error
of 0.91, and a linear correlation coefficient of 0.79. Though this level of
accuracy is similar to the GBSW-based CpHMD in CHARMM, in contrast to the latter,
the current implementation was able to reproduce the experimental orders of the p
Ka's of the coupled carboxylic dyads. We quantified the sampling errors, which
revealed that prolonged simulation is needed to converge p Ka's of several
titratable groups involved in salt-bridge-like interactions or deeply buried in
the protein interior. Our benchmark data demonstrate that GBNeck2-CpHMD is an
attractive tool for protein p Ka predictions.
PMID- 29949357
TI - Climate, Fire, and Vegetation Mediate Mercury Delivery to Midlatitude Lakes over
the Holocene.
AB - The rise in mercury concentrations in lake sediment deposited over the last ~150
years is widely recognized to have resulted from human activity. However, few
studies in the Great Lakes region have used lake sediment to reconstruct
atmospheric mercury deposition on millennial time scales. Here we present a 9000
year mercury record from sediment in Copper Falls; a small closed-basin lake on
the Keweenaw Peninsula. Prior to abrupt increases in the 19th and 20th centuries,
mercury remains at relatively low concentrations for the last 9000 years. Higher
mercury fluxes in the early Holocene (3.4 +/- 1.1 MUg m-2 yr-1) are attributed to
drier conditions and greater forest fire occurrence. The gradual decline in
mercury flux over the middle to late Holocene (1.9 +/- 0.2 MUg m-2 yr-1) is
interpreted to reflect a transition to wetter conditions, which reduced forest
fires, and promoted the development of soil organic matter and deciduous forests
that sequestered natural sources of mercury. The Copper Falls Lake record
highlights the sensitivity of watersheds to changes in mercury inputs from both
human and natural forcings, and provides millennial-scale context for recent
mercury contamination that will aid in establishing baseline values for
restoration efforts.
PMID- 29949358
TI - Virtual Screening of Hole Transport, Electron Transport, and Host Layers for
Effective OLED Design.
AB - The alignment of energy levels within an OLED device is paramount for high
efficiency performance. In this study, the emissive, electron transport, and hole
transport layers are consecutively evolved under the constraint of fixed
electrode potentials. This materials development strategy takes into
consideration the full multilayer OLED device, rather than just individual
components. In addition to introducing this protocol, an evolutionary method, a
genetic algorithm (GA), is evaluated in detail to increase its efficiency in
searching through a library of 30 million organic compounds. On the basis of the
optimization of the variety of GA parameters and selection methods, an
exponential ranking selection protocol with a high mutation rate is found to be
the preferred method for quickly identifying the top-performing molecules within
the large chemical space. This search through OLED materials space shows that the
pyridine-based central core with acridine-based fragments are good target host
molecules for common electrode materials. Additionally, weak electron-donating
groups, such as naphthalene- and xylene-based fragments, appear often in the
optimal electron-transport layer materials. Triphenylamine- and acridine-based
fragments, due to their strong electron-donating character, were found to be good
candidates for the hole-transport layer.
PMID- 29949359
TI - Reversible Triplet Excitation Transfer in a Trimethylene-Linked Thioxanthone and
Benzothiophene-2-Carboxanilide that Photochemically Expels Leaving Group Anions.
AB - The triplet excited state of thioxanthone produced by photolysis undergoes
reversible triplet energy transfer with a trimethylene-linked benzothiophene-2
carboxanilide ring system. The ensuing electrocyclic ring closure of the anilide
moiety produces a putative zwitterionic intermediate that is capable of expelling
leaving groups (LG-) from the C-3 position of the benzothiophene ring. Stern
Volmer quenching studies with cyclohexadiene as quencher furnish the rate
constants for the triplet excitation transfer in the forward and reverse
directions, which can be expressed as an equilibrium constant K = 0.058. Overall,
the rate of the triplet excited state reaction becomes K * kr = 5.7 * 104 s-1 for
LG- = Cl-, where kr is the triplet decay rate of the C-3 chloro-substituted
benzothiophene-2-carboxanilide, found through Stern-Volmer quenching. The high
quantum efficiencies found for the trimethylene-linked systems are due to K * kr
being competitive with the triplet excited state decay of the thioxanthone of kd
= 7.7 * 104 s-1. On the basis of Phiisc = 0.68, the overall expected quantum
yield for direct photolysis should be 0.50 for LG- = Cl- as compared to 0.41 at
25 degrees C experimentally. Phi decreases with increasing basicity of the
leaving group (LG- = Cl-, (EtO)2PO2-, PhCH2CO2-, PhS-, and PhCH2S-).
PMID- 29949360
TI - QSAR Modeling of ToxCast Assays Relevant to the Molecular Initiating Events of
AOPs Leading to Hepatic Steatosis.
AB - Nonalcoholic hepatic steatosis is a worldwide epidemiological concern since it is
among the most prominent hepatic diseases. Indeed, research in toxicology and
epidemiology has gathered evidence that exposure to endocrine disruptors can
perturb cellular homeostasis and cause this disease. Therefore, assessing the
likelihood of a chemical to trigger hepatic steatosis is a matter of the utmost
importance. However, systematic in vivo testing of all the chemicals humans are
exposed to is not feasible for ethical and economical reasons. In this context,
predicting the molecular initiating events (MIE) leading to hepatic steatosis by
QSAR modeling is an issue of practical relevance in modern toxicology. In this
article, we present QSAR models based on random forest classifiers and DRAGON
molecular descriptors for the prediction of in vitro assays that are relevant to
MIEs leading to hepatic steatosis. These assays were provided by the ToxCast
program and proved to be predictive for the detection of chemical-induced
steatosis. During the modeling process, special attention was paid to chemical
and toxicological data curation. We adopted two modeling strategies
(undersampling and balanced random forests) to develop robust QSAR models from
unbalanced data sets. The two modeling approaches gave similar results in terms
of predictivity, and most of the models satisfy a minimum percentage of correctly
predicted chemicals equal to 75%. Finally, and most importantly, the developed
models proved to be useful as an effective in silico screening test for hepatic
steatosis.
PMID- 29949361
TI - Achieving a High Areal Capacity with a Binder-Free Copper Molybdate Nanocone
Array-Based Positive Electrode for Hybrid Supercapacitors.
AB - Herein, we develop a binder-free copper molybdate nanocone array with a prism
like morphology on nickel foam (Cu3Mo2O9 NCAs/Ni foam) using a single-step
hydrothermal method. With an optimal growth time (10 h) under hydrothermal
conditions, the prism-like Cu3Mo2O9 NCAs are uniformly decorated on Ni foam with
good adhesion and crystallinity. The prepared Cu3Mo2O9 NCAs/Ni foam has been
directly used as a binder-free electrode to examine its suitability as a positive
electrode in hybrid supercapacitors. In an aqueous 1 M KOH electrolyte, the
binder-free Cu3Mo2O9 NCAs/Ni foam showed battery-type behavior with a high areal
capacity of 449.5 MUAh cm-2 at a discharge current density of 2 mA cm-2 and also
exhibited a good cycling stability. In addition, the pouch-type hybrid
supercapacitor is assembled using the prism-like Cu3Mo2O9 NCAs/Ni foam as a
positive electrode and the activated carbon as a negative electrode in a 1 M KOH
electrolyte. The hybrid supercapacitor achieves a maximum cell potential of 1.6 V
with superior energy storage properties, including a high areal capacitance of
609.7 mF cm-2 at 3.5 mA cm-2, a high areal energy (0.21 mWh cm-2), and a high
power density (2.73 mW cm-2). The obtained results suggest that the facilely
synthesized Cu3Mo2O9 NCAs/Ni foam electrode has great potential in high
performance energy storage devices.
PMID- 29949362
TI - New High Pressure Phases of Energetic Material TEX: Evidence from Raman
Spectroscopy, X-ray Diffraction, and First-Principles Calculations.
AB - Samples of energetic material TEX (C6H6N4O8) are studied using Raman spectroscopy
and X-ray diffraction (XRD) up to 27 GPa pressure. There are clear changes in the
Raman spectra and XRD patterns around 2 GPa related to a conformational change in
the TEX molecule, and a phase transformation above 11 GPa. The molecular
structures and vibrational frequencies of TEX are calculated by density
functional theory based Gaussian 09W and CASTEP programs. The computed
frequencies compare well with Raman spectroscopic results. Mode assignments are
carried out using the vibrational energy distribution analysis program and are
also visualized in the Materials Studio package. Raman spectra of the high
pressure phases indicate that the sensitivity of these phases is more than that
of the ambient phase.
PMID- 29949363
TI - Topotactic Transformation of Solvated MgCr-LDH Nanosheets to Highly Efficient
Porous MgO/MgCr2O4 Nanocomposite for Photocatalytic H2 Evolution.
AB - The hybrid structure of nanoparticles (NPs) with nanosheets has the advantage of
both anisotropic properties of NPs and large specific surface areas of
nanosheets, which is desirable for many technological applications. In this
study, MgCr2O4 spinel NPs decorated on highly porous MgO nanosheets forming
MgO/MgCr2 O4( x) nanocomposites were synthesized by a one pot coprecipitation
method followed by a heat treatment process of the solvated wet gel of MgCr-LDH
with polar solvent N, N-dimethylformamide (DMF) at 400 degrees C. This novel
synthetic methodology generates materials consisting of porous metal oxides
nanosheets adhered with spinel phase NPs due to the slow generation of gases such
as H2O, CO2, and NH3 under moderate temperature during the heat treatment
process. The synergistic effect of much wider band gap MgO nanosheets and narrow
band gap MgCr2O4 NPs added increased stability due to the stronger bonding
coordination of MgCr2O4 NPs with MgO nanosheets. The obtained MgO/MgCr2 O4( x)
nanocomposites possess large specific surface areas, highly porous structure, and
excellent interface between MgCr2O4 NPs and MgO nanosheets, which proved from N2
sorption isotherm, TEM, HR-TEM study. With metallic ratio of MgCr3:1,
MgO/MgCr2O4(MgCr3:1) nanocomposites exhibit highest H2 evolution rate of 840
MUmolg-12h-1, which was 2 times higher than that of pure MgCr2O4(420 MUmolg-12h
1). The LSV measurement study of MgO/MgCr2O4 (MgCr3:1) nanocomposite shows an
enhancement of light current density of 0.22 MUA/cm2 at potential bias of -1.1 V.
The Mott-Schottky analysis suggested the band edge positions of the n-type
constituents and formation of n-n type heterojunctions in MgO/MgCr2O4 (MgCr3:1)
nanocomposite, which facilitates the flow of charge carriers. The EIS and Bode
phase plot of MgO/MgCr2O4 (MgCr3:1) nanocomposite signifies the lower interfacial
charge transfer resistance and higher lifetime of electrons (2.7 ms) for enhanced
H2 production. Lastly, the enhanced photocatalytic H2 production activity and
long-term stability of MgO/MgCr2O4(MgCr3:1) could be attributed to maximum
specific surface area, porous structure, close intimacy contact angle between two
cubic phases of MgCr2O4 NPs and MgO nanosheets, abundant oxygen vacancies sites,
reduced charge transfer resistance and suitable band edge potential to drive the
thermodynamic energy for H2 production. This work highlighted an effective
strategy for the synthesis of cost-effective 2D porous heterojunctions
nanocomposite photocatalyst for promising applications in the field of clean H2
production utilizing abundant solar energy.
PMID- 29949364
TI - Dicarbonyl cis-[M(CO)2(N,O)(C)(P)] (M = Re, 99mTc) Complexes with a New [2 + 1 +
1] Donor Atom Combination.
AB - The synthesis and characterization of the dicarbonyl mixed ligand cis
[Re(CO)2(quin)(cisc)(PPh3)] complex, 4, where quin is the deprotonated quinaldic
acid, cisc is cyclohexyl isocyanide, and PPh3 is triphenylphosphine, is
presented. The synthesis of 4 proceeds in three steps. In the first, the
intermediate fac-[Re(CO)3(quin)(H2O)] aqua complex 2 is generated from the fac
[NEt4]2[Re(CO)3Br3] precursor, together with the brominated products fac
[Re(CO)3(quinH)(Br)] 1a and fac-[NEt4][Re(CO)3(quin)(Br)] 1b, in low yield. In
the following step, replacement of the aqua ligand of complex 2 by the
monodentate isocyanide ligand leads to the formation of fac
[Re(CO)3(quin)(cisc)], 3. In the third step replacement of the species trans to
the isocyanide carbonyl group of 3 by a phosphine generates complex 4. The Re
complexes 2-4 were prepared in high yield and fully characterized by elemental
analysis, spectroscopic methods, and X-ray crystallography. At the technetium-99m
(99mTc) tracer level, the analogous complexes 3' and 4' were produced in high
radiochemical purity, characterized by comparative reverse phase high-performance
liquid chromatography and showed high resistance to transchelation by histidine
or cysteine. This new [N,O][C][P] donor atom combination with the cis-[M(CO)2]+
core (M = Re, 99mTc) is a promising scaffold for the development of novel
diagnostic and therapeutic targeted radiopharmaceuticals.
PMID- 29949365
TI - Hexavalent Chromium Sources and Distribution in California Groundwater.
AB - Groundwater resources in California represent a confluence of high-risk factors
for hexavalent chromium contamination as a result of industrial activities,
natural geology, and, potentially, land use. Here, we examine state-wide links in
California between groundwater Cr(VI) concentrations and chemicals that provide
signatures for source attribution. In environmental monitoring wells, Cr(VI) had
the highest co-occurrence and also clustered with 1,4-dioxane and several
chlorinated hydrocarbons indicative of the metal plating industry. Additionally,
hotspots of Cr(VI) co-occurring with bromoform result from volatile organic
compound remediation using in situ chemical oxidation that inadvertently oxidizes
naturally occurring Cr(III). In groundwater supply wells, which are typically
free of industrial inputs, Cr(VI) correlates with
dichlorodiphenyldichloroethylene (DDE), vanadium, and ammonia and clusters with
nitrate and dissolved oxygen, suggesting potential links between agricultural
activities and Cr(VI). Specific controls on Cr(VI) vary substantially by region:
from the metal plating industry around Los Angeles and the San Francisco Bay
areas to natural redox conditions along flow paths in the Mojave Desert and to
correlations with agricultural practices in the Central Valley of California.
While industrial uses of Cr lead to the most acute cases of groundwater Cr(VI)
contamination, oxidation of naturally occurring Cr affects a larger area, more
wells, and a greater number of people throughout California.
PMID- 29949366
TI - General Approach to Estimate Error Bars for Quantitative Structure-Activity
Relationship Predictions of Molecular Activity.
AB - Key requirements for quantitative structure-activity relationship (QSAR) models
to gain acceptance by regulatory authorities include a defined domain of
applicability (DA) and appropriate measures of goodness-of-fit, robustness, and
predictivity. Hence, many DA metrics have been developed over the past two
decades. The most intuitive are perhaps distance-to-model metrics, which are most
commonly defined in terms of the mean distance between a molecule and its k
nearest training samples. Detailed evaluations have shown that the variance of
predictions by an ensemble of QSAR models may serve as a DA metric and can
outperform distance-to-model metrics. Intriguingly, the performance of ensemble
variance metric has led researchers to conclude that the error of predicting a
new molecule does not depend on the input descriptors or machine-learning methods
but on its distance to the training molecules. This implies that the distance to
training samples may serve as the basis for developing a high-performance DA
metric. In this article, we introduce a new Tanimoto distance-based DA metric
called the sum of distance-weighted contributions (SDC), which takes into account
contributions from all molecules in a training set. Using four acute chemical
toxicity data sets of varying sizes and four other molecular property data sets,
we demonstrate that SDC correlates well with the prediction error for all data
sets regardless of the machine-learning methods and molecular descriptors used to
build the QSAR models. Using the acute toxicity data sets, we compared the
distribution of prediction errors with respect to SDC, the mean distance to k
nearest training samples, and the variance of random forest predictions. The
results showed that the correlation with the prediction error was highest for
SDC. We also demonstrate that SDC allows for the development of robust root mean
squared error (RMSE) models and makes it possible to not only give a QSAR
prediction but also provide an individual RMSE estimate for each molecule.
Because SDC does not depend on a specific machine-learning method, it represents
a canonical measure that can be widely used to estimate individual molecule
prediction errors for any machine-learning method.
PMID- 29949367
TI - Restricted Open-Shell Configuration Interaction Singles Study on M- and L-edge X
ray Absorption Spectroscopy of Solid Chemical Systems.
AB - In this study the M- and L-edge X-ray absorption spectra of a series of open- and
closed-shell solids (TiO2 rutile, alpha-Fe2O3 hematite, FeS2 pyrite, and the
spinel Co3O4) are investigated with the restricted open-shell configuration
interaction singles methods (ROCIS/DFT and PNO-ROCIS/DFT) using the embedded
cluster approach. ROCIS/DFT type of methods are grounded in wave function-based
ab initio electronic structure theory and have shown great performance in the
field of X-ray spectroscopy in particular in the field of transition metal L-edge
spectroscopy. In this work we show that ROCIS/DFT can be used to calculate and
interpret metal M- and L-edge XAS spectra of solids. To this end, clusters with
up to 52 metal centers are considered. In all cases good to excellent agreement
between theory and experiment is obtained. The experimentally probed local
coordination environments are discussed in detail. The physical origin of the
observed spectral features is explored through the machinery of natural
difference orbitals. This analysis provides valuable information with respect to
the core to valence, metal to metal charge transfer, and metal to ligand charge
transfer characters of the relativistically corrected many particle states. The
influence of the above electronic effects to the spectral shapes and the size of
the treated clusters are thoroughly investigated.
PMID- 29949368
TI - Mixed-Valence Superstructure Assembled from a Mixed-Valence Host-Guest Complex.
AB - Herein, we report an unprecedented mixed-valence crystal superstructure that
consists of a 2:1 host-guest complex [MV?(CBPQT)2]2/3+ [MV = methyl viologen,
CBPQT = cyclobis(paraquat- p-phenylene)]. One electron is distributed
statistically between three [MV?(CBPQT)2]*+ composed of a total of 15 viologen
units. The mixed-valence state is validated by single-crystal X-ray
crystallography, which supports an empirical formula of [MV?(CBPQT)2]3.(PF6)2 for
the body-centered cubic superstructure. Electron paramagnetic resonance provides
further evidence of electron delocalization. Quantum chemistry calculations
confirm the mixed-valence state in the crystal superstructure. Our findings
demonstrate that precise tuning of the redox states in host-guest systems can
lead to a promising supramolecular strategy for achieving long-range electron
delocalization in solid-state devices.
PMID- 29949369
TI - 3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and
Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein
Degradation.
AB - Hydroxylation and fluorination of proline alters the pyrrolidine ring pucker and
the trans:cis amide bond ratio in a stereochemistry-dependent fashion, affecting
molecular recognition of proline-containing molecules by biological systems.
While hydroxyprolines and fluoroprolines are common motifs in medicinal and
biological chemistry, the synthesis and molecular properties of prolines
containing both modifications, i.e., fluoro-hydroxyprolines, have not been
described. Here we present a practical and facile synthesis of all four
diastereoisomers of 3-fluoro-4-hydroxyprolines (F-Hyps), starting from readily
available 4-oxo-l-proline derivatives. Small-molecule X-ray crystallography, NMR
spectroscopy, and quantum mechanical calculations are consistent with
fluorination at C3 having negligible effects on the hydrogen bond donor capacity
of the C4 hydroxyl, but inverting the natural preference of Hyp from C4-exo to C4
endo pucker. In spite of this, F-Hyps still bind to the von Hippel-Lindau (VHL)
E3 ligase, which naturally recognizes C4-exo Hyp in a stereoselective fashion. Co
crystal structures and electrostatic potential calculations support and
rationalize the observed preferential recognition for (3 R,4 S)-F-Hyp over the
corresponding (3 S,4 S) epimer by VHL. We show that (3 R,4 S)-F-Hyp provides
bioisosteric Hyp substitution in both hypoxia-inducible factor 1 alpha (HIF
1alpha) substrate peptides and peptidomimetic ligands that form part of PROTAC
(proteolysis targeting chimera) conjugates for targeted protein degradation.
Despite a weakened affinity, Hyp substitution with (3 S,4 S)-F-Hyp within the
PROTAC MZ1 led to Brd4-selective cellular degradation at concentrations >100-fold
lower than the binary Kd for VHL. We anticipate that the disclosed chemistry of 3
fluoro-4-hydroxyprolines and their application as VHL ligands for targeted
protein degradation will be of wide interest to medicinal organic chemists,
chemical biologists, and drug discoverers alike.
PMID- 29949370
TI - Electronic and Steric Tuning of Catalytic H2 Evolution by Cobalt Complexes with
Pentadentate Polypyridyl-Amine Ligands.
AB - Structural modifications of molecular cobalt catalysts have provided important
insights into the structure-function relationship for the hydrogen evolution
reaction. We have shown that replacement of equatorial pyridines with more basic
and conjugate isoquinoline groups of a pentadentate ligand results in lower
overpotential and higher catalytic activity for electro- and photolytic H2
production in aqueous solutions. To fully understand the electronic and steric
effects of the axial group that lies trans to the proposed cobalt hydride
intermediate, isoquinoline groups were introduced in two new pentadentate
ligands, N, N-bis(2-pyridinylmethyl)[3-(2-pyridinyl)isoquinoline)]-1-methanamine
(DPA-1-MPI) and N, N-bis(2-pyridinylmethyl)[1-(2-pyridinyl)-isoquinoline)]-3
methanamine (DPA-3-MPI). Despite a slight structural difference of the introduced
isoquinoline group, the resulting cobalt complexes display drastic changes in
their electro- and photochemical properties. There are positive shifts of 290 and
260 mV, respectively, for the CoII/CoI and CoIII-H/CoII-H couples from [Co(DPA-1
MPI)(H2O)](PF6)3 to [Co(DPA-3-MPI)(H2O)](PF6)3, with the former being ~32 times
as active as the latter in photocatalytic H2 production. Density functional
theory (DFT) calculations show that the protonation of CoI to yield the CoIII-H
species is energetically more favorable for [Co(DPA-1-MPI)(H2O)](PF6)3 than that
of [Co(DPA-3-MPI)(H2O)](PF6)3. Both experimental results and DFT computations
suggest that the presence of a planar conjugate bipyridyl unit or its
isoquinoline derivative is a key feature for stabilizing low valent CoI species
toward proton binding. The incorporation of an electron-donating group trans to
the proposed Co-H species also facilitates proton binding and H-H bond formation,
which is proposed to occur by the heterolytic coupling of CoII-H species. The
overall catalytic H2 evolution is presented as the modified electron transfer (E)
proton transfer (C)-electron transfer (E)-proton transfer (C) (mod-ECEC) pathway.
This study provides important new insight into the electronic and steric factors
controlling catalytic H2 production by Co complexes with pentadentate ligands.
PMID- 29949371
TI - Singlet Fission in Covalent Terrylenediimide Dimers: Probing the Nature of the
Multiexciton State Using Femtosecond Mid-Infrared Spectroscopy.
AB - Singlet fission (SF) is a spin-allowed process that involves absorption of a
photon by two electronically interacting chromophores to produce a singlet
exciton state, 1(S1S0), followed by rapid formation of two triplet excitons if
the singlet exciton energy is about twice that of the triplet exciton. The
initial formation of the multiexciton correlated triplet pair state, 1(T1T1), is
thought to involve the agency of charge transfer (CT) states. The dynamics of
these electronic states were studied in a covalent slip-stacked terrylene
3,4:11,12-bis(dicarboximide) (TDI) dimer in which the conformation of two TDI
molecules is determined by a xanthene spacer (XanTDI2). Femtosecond mid-infrared
(fsIR) spectroscopy shows that the multiexciton 1(T1T1) state has absorptions
characteristic of the T1 state in the carbonyl stretch region of the IR spectrum,
in addition to IR absorptions specific to the CT state in the C?C stretch region.
The simultaneous presence of CT and triplet state features in both high
dielectric constant CH2Cl2 and low dielectric constant 1,4-dioxane throughout the
multiexciton state lifetime suggests that this state has both CT and triplet
character.
PMID- 29949372
TI - Thorium(IV) and Uranium(IV) Complexes with Cucurbit[5]uril.
AB - Tetravalent thorium and uranium complexes with cucurbit[5]uril (Q[5]) were
investigated with eight new complexes being synthesized and structurally
characterized. [Th(Q[5])(OH)(H2O)2]6.18NO3. nH2O (1) has a hexagonal nanowheel
structure with each of the six Th4+ ions being cap-coordinated by a Q[5] and
monodentate-coordinated to the nearby Q[5].
[Th(Q[5])(HCOO)(H2O)4][Th(NO3)5(H2O)2]2[Th(NO3)3(HCOO)(H2O)2]0.5.NO3. nH2O (2)
has a heteroleptic mononuclear structure with a Th4+ ion cap-coordinated on one
side of the Q[5] portal and monodentate-coordinated to a formate anion inside the
Q[5] cavity. [KTh1.5(Q[5])Cl(NO3)3][Th(NO3)5(H2O)2].2NO3.2.5H2O (3) has a
heterometallic structure with both Th4+ and K+ ions each occupying one side of
the two Q[5] portals forming a capsule. [CsTh(Q[5])Cl(NO3)2(H2O)3].2NO3. nH2O (4)
has a heterometallic 1D polymeric structure with both Th4+ and Cs+ ions each
occupying one side of the two Q[5] portals, forming monomers which are linked
together by sharing two water molecules and one carbonyl oxygen atom between Th4+
and Cs+ ions. [Th(Q[5])Cl(H2O)][CdCl3][CdCl4].0.5HCl.4H2O (5),
[Th(Q[5])Cl(H2O)][Ru2OCl9(H2O)].0.5HCl.9.5H2O (6),
[Th(Q[5])Cl(H2O)][IrCl6]1.5.3H2O (7), and
[U(Q[5])Cl(H2O)][ZnCl3(H2O)][(ZnCl4)].8H2O (8) have similar 1D polymeric
structures with Th4+/U4+ ions cap-coordinated on one side of a Q[5] and bidentate
coordinated to the nearby Q[5]. The transition metal chlorides act as anions for
charge compensation as well as structure inducers via cation-anion interactions
forming various anion patterns around the 1D polymers. Actinide contraction has
been observed in the early actinide series.
PMID- 29949373
TI - Network Structure and Connectivity in SnO-P2O5 Glasses: Results from 2D 31P and
119Sn NMR Spectroscopy.
AB - The compositional evolution of the network structure and connectivity in binary
SnO-P2O5 glasses with 35 <= mol % SnO <= 55 is studied using two-dimensional
119Sn and 31P NMR spectroscopy. The phosphate Q n species concentrations, as
obtained from the analyses of the 31P NMR spectral line shapes suggest that the
network modification can be described in terms of a binary Q-speciation model. On
the other hand, the 119Sn NMR spectra suggest that the Sn-O coordination
environment in these glasses is composition dependent. Sn is present in both 3
fold (trigonal pyramid) and 4-fold (trigonal bipyramid) coordinations with oxygen
in these glasses. The relative fraction of the trigonal pyramidal environment
increases with increasing SnO content. The unusually low glass transition
temperature Tg of these glasses (241-266 degrees C) is argued to be related to
the low coordination number of Sn, leading to a relatively sparsely connected
structural network.
PMID- 29949374
TI - Multi-Valley Superconductivity in Ion-Gated MoS2 Layers.
AB - Layers of transition metal dichalcogenides (TMDs) combine the enhanced effects of
correlations associated with the two-dimensional limit with electrostatic control
over their phase transitions by means of an electric field. Several
semiconducting TMDs, such as MoS2, develop superconductivity (SC) at their
surface when doped with an electrostatic field, but the mechanism is still
debated. It is often assumed that Cooper pairs reside only in the two electron
pockets at the K/K' points of the Brillouin Zone. However, experimental and
theoretical results suggest that a multivalley Fermi surface (FS) is associated
with the SC state, involving six electron pockets at Q/Q'. Here, we perform low
temperature transport measurements in ion-gated MoS2 flakes. We show that a fully
multivalley FS is associated with the SC onset. The Q/Q' valleys fill for doping
? 2 * 1013 cm-2, and the SC transition does not appear until the Fermi level
crosses both spin-orbit split sub-bands Q 1 and Q 2. The SC state is associated
with the FS connectivity and promoted by a Lifshitz transition due to the
simultaneous population of multiple electron pockets. This FS topology will serve
as a guideline in the quest for new superconductors.
PMID- 29949375
TI - Gate-Defined Electron-Hole Double Dots in Bilayer Graphene.
AB - We present gate-controlled single-, double-, and triple-dot operation in
electrostatically gapped bilayer graphene. Thanks to the recent advancements in
sample fabrication, which include the encapsulation of bilayer graphene in
hexagonal boron nitride and the use of graphite gates, it has become possible to
electrostatically confine carriers in bilayer graphene and to completely pinch
off current through quantum dot devices. Here, we discuss the operation and
characterization of electron-hole double dots. We show a remarkable degree of
control of our device, which allows the implementation of two different gate
defined electron-hole double-dot systems with very similar energy scales. In the
single-dot regime, we extract excited state energies and investigate their
evolution in a parallel magnetic field, which is in agreement with a Zeeman-spin
splitting expected for a g-factor of 2.
PMID- 29949376
TI - Binding of HSA to Macromolecular pHPMA Based Nanoparticles for Drug Delivery: An
Investigation Using Fluorescence Methods.
AB - Amphiphilic poly( N-(2-hydroxypropyl)methacrylamide) copolymers ( pHPMA) bearing
cholesterol side groups in phosphate buffer saline self-assemble into
nanoparticles (NPs) which can be used as tumor-targeted drug carriers. It was
previously shown by us that human serum albumin (HSA) interacts weakly with the
NPs. However, the mechanism of this binding could not be resolved due to
overlapping of signals from the complex system. Here, we use fluorescence
labeling to distinguish the components and to characterize the binding: On the
one hand, a fluorescent dye was attached to pHPMA, so that the diffusion behavior
of the NPs could be studied in the presence of HSA using fluorescence lifetime
correlation spectroscopy. On the other hand, quenching of the intrinsic
fluorescence of HSA revealed the origin of the binding, which is mainly the
complexation between HSA and cholesterol side groups. Furthermore, a binding
constant was obtained.
PMID- 29949377
TI - Optical Manipulation along an Optical Axis with a Polarization Sensitive Meta
Lens.
AB - The ability to manipulate small objects with focused laser beams opens a broad
spectrum of opportunities in fundamental and applied studies, for which precise
control over mechanical path and stability is required. Although conventional
optical tweezers are based on refractive optics, the development of compact
trapping devices that could be integrated within fluid cells is in high demand.
Here, a plasmonic polarization-sensitive metasurface-based lens, embedded within
a fluid, is demonstrated to provide several stable trapping centers along the
optical axis. The position of a particle is controlled with the polarization of
the incident light, interacting with plasmonic nanoscale patch antennas,
organized within overlapping Fresnel zones of the lens. While standard
diffractive optical elements face challenges in trapping objects in the axial
direction outside the depth of focus, bifocal Fresnel meta-lens demonstrates the
capability to manipulate a bead along a 4 MUm line. An additional fluorescent
module, incorporated within the optical trapping setup, was implemented and
enabled the accurate mapping of optical potentials via a particle-tracking
algorithm. Auxiliary micro- and nanostructures, integrated within fluidic
devices, provide numerous opportunities to achieve flexible optomechanical
manipulation, including transport, trapping, and sorting, which are in high
demand for lab-on-a-chip applications and many others.
PMID- 29949378
TI - Multiscale Mechanics of Triply Periodic Minimal Surfaces of Three-Dimensional
Graphene Foams.
AB - The mechanics of triply periodic minimal surfaces (TPMSs) with three-dimensional
(3D) graphene foams are systematically studied to understand the effects of
structure and size on the mechanical properties, for example, elasticity,
strength, and fracture. The design of lightweight open-shell porous solid
materials with TPMSs has shown excellent and tunable load-bearing properties.
However, fracture properties and their relations with surface topologies are
largely unknown. Utilizing reactive molecular dynamics simulations, here we
investigate the elastic and fracture properties of three different surface
topologies with 3D graphene foams: P (primitive), D (diamond), and G (gyroid),
called Schwarzites. Models with different lattice sizes are utilized to derive
power laws, which can connect the properties along different sizes to shed light
on the multiscale mechanics of TPMSs. Our study provides a systematic
understanding of the relation between TPMS topologies and their mechanical
properties, including failure mechanisms of graphene foams, opening opportunities
to explore designable structures with tailored properties.
PMID- 29949379
TI - Interpretation of Spirometry in Saskatchewan First Nations Adults.
PMID- 29949380
TI - Choice of Initial Oral Therapy for Pulmonary Arterial Hypertension: Age and Long
Term Survival.
PMID- 29949381
TI - Emerging roles of extracellular vesicles in cardiac repair and rejuvenation.
AB - Cell therapy has received significant attention as a therapeutic approach to
restore cardiac function after myocardial infarction. Accumulating evidence
supports that beneficial effects observed with cell therapy are due to paracrine
secretion of multiple factors from transplanted cells, which alter the tissue
microenvironment and orchestrate cardiac repair processes. Of these paracrine
factors, extracellular vesicles (EVs) have emerged as a key effector of cell
therapy. EVs regulate cellular function through the transfer of cargo, such as
microRNAs and proteins, which act on multiple biological pathways within
recipient cells. These discoveries have led to the development of cell-free
therapies using EVs to improve cardiac repair after a myocardial infarction.
Here, we present an overview of the current use of EVs to enhance cardiac repair
after myocardial infarction. We also discuss the emerging use of EVs for
rejuvenation-based therapies. Finally, future directions for the use of EVs as
therapeutic agents for cardiac regenerative medicine are also discussed.
PMID- 29949383
TI - Return to Sport After Surgical Treatment for Anterior Shoulder Instability: A
Systematic Review.
AB - BACKGROUND: For athletes, a return to preinjury activity levels with minimal time
away is a metric indicative of successful recovery. The knowledge of this metric
would be helpful for the sports medicine specialist to advise patients on
appropriate expectations after surgery. PURPOSE: To evaluate the rate and amount
of time needed for athletes to return to sport (RTS) after different surgical
treatments for anterior shoulder instability. STUDY DESIGN: Systematic review and
meta-analysis. METHODS: The MEDLINE, EMBASE, and Cochrane databases were searched
for articles relevant to athletes' RTS after surgical anterior shoulder
stabilization with variants of the Latarjet and Bankart procedures. Article
selection was based on relevant inclusion and exclusion criteria. After the
articles were reviewed, the data pertinent to rates of and time to RTS were
extracted, compiled, and analyzed. RESULTS: Sixteen articles met the inclusion
criteria. Based on these articles, the rate of RTS was 97.5% after arthroscopic
Bankart, 86.1% after open Bankart, 83.6% after open Latarjet, 94.0% after
arthroscopic Latarjet, and 95.5% after arthroscopic Bankart with remplissage.
Among the athletes who did RTS, arthroscopic Bankart had the highest rate of
return to preinjury levels (91.5%), while arthroscopic Latarjet had the lowest
rate (69.0%). The time to RTS was 5.9 months after arthroscopic Bankart, 8.2
months after open Bankart, 5.07 months after open Latarjet, 5.86 months after
arthroscopic Latarjet, and 7 months after arthroscopic Bankart with remplissage.
CONCLUSION: Of the pooled data, patients who underwent arthroscopic Bankart
showed the highest rate of RTS, while patients who underwent open Latarjet showed
the shortest time to RTS. Return to preinjury level was highest in the
arthroscopic Bankart group and lowest in the arthroscopic Latarjet group.
Physicians can utilize these data to set expectations for their patient-athletes
regarding RTS after anterior shoulder stabilization procedures. CLINICAL
RELEVANCE: When treating an athlete, many factors must be taken into account to
weigh treatment options. Two important factors to consider with the patient
athlete are the rate of return to the previous activity level and the timeline
for this to occur. This study provides a guide for physicians and a time frame
for athletes with respect to the mean percentage and time for return to sport
after different surgical procedures for anterior shoulder instability.
PMID- 29949382
TI - A novel fibroblast activation inhibitor attenuates left ventricular remodeling
and preserves cardiac function in heart failure.
AB - Cardiac fibroblasts are critical mediators of fibrotic remodeling in the failing
heart and transform into myofibroblasts in the presence of profibrotic factors
such as transforming growth factor-beta. Myocardial fibrosis worsens cardiac
function, accelerating the progression to decompensated heart failure (HF). We
investigated the effects of a novel inhibitor (NM922; NovoMedix, San Diego, CA)
of the conversion of normal fibroblasts to the myofibroblast phenotype in the
setting of pressure overload-induced HF. NM922 inhibited fibroblast-to
myofibroblast transformation in vitro via a reduction of activation of the focal
adhesion kinase-Akt-p70S6 kinase and STAT3/4E-binding protein 1 pathways as well
as via induction of cyclooxygenase-2. NM922 preserved left ventricular ejection
fraction ( P < 0.05 vs. vehicle) and significantly attenuated transverse aortic
constriction-induced LV dilation and hypertrophy ( P < 0.05 compared with
vehicle). NM922 significantly ( P < 0.05) inhibited fibroblast activation, as
evidenced by reduced myofibroblast counts per square millimeter of tissue area.
Picrosirius red staining demonstrated that NM922 reduced ( P < 0.05) interstitial
fibrosis compared with mice that received vehicle. Similarly, NM922 hearts had
lower mRNA levels ( P < 0.05) of collagen types I and III, lysyl oxidase, and TNF
alpha at 16 wk after transverse aortic constriction. Treatment with NM922 after
the onset of cardiac hypertrophy and HF resulted in attenuated myocardial
collagen formation and adverse remodeling with preservation of left ventricular
ejection fraction. Future studies are aimed at further elucidation of the
molecular and cellular mechanisms by which this novel antifibrotic agent protects
the failing heart. NEW & NOTEWORTHY Our data demonstrated that a novel
antifibrotic agent, NM922, blocks the activation of fibroblasts, reduces the
formation of cardiac fibrosis, and preserves cardiac function in a murine model
of heart failure with reduced ejection fraction.
PMID- 29949384
TI - Exploring the complexity: the interplay between the angiotensin-converting enzyme
insertion/deletion polymorphism and the sympathetic response to hemodialysis.
AB - Patients on hemodialysis (HD) are at increased risk for arrhythmias and sudden
cardiac death. Autonomic nervous system (ANS) dysfunction seems to participate in
the arrhythmogenic process. Genetic factors have an impact on ANS modulation, but
the specific role of the insertion/deletion (I/D) polymorphism in the gene for
angiotensin-converting enzyme (ACE) has not been investigated. Since the D allele
increases gene expression, it is a candidate polymorphism to interact with the
ANS. The aim of the present study was to compare the behavior of heart rate
variability (HRV) during HD, as a surrogate for ANS response to stressors,
between the ACE genotypes. In a sample of patients with chronic kidney disease
I/D ACE genotypes were assessed with PCR and HRV was measured before, in the
second hour, and after a HD session. HRV parameters in the time and frequency
domains were analyzed by repeated-measures mixed models according to the time of
measurement and ACE polymorphism. HRV parameters in the frequency domain
presented significantly different variations during the HD session between
patients with or without the D allele. Only patients with the II genotype
presented an increase in low-frequency normalized units and in the low frequency
to-high frequency ratio throughout HD. Patients with the II genotype seemed to
have a more physiological response to the volemic and electrolytic changes that
occur during HD, with greater sympathetic activation than patients with ID and DD
genotypes. NEW & NOTEWORTHY Adding to the effort to understand the complexity of
cardiovascular system regulation, we have found that the autonomic nervous system
response to the acute volume removal during hemodialysis may be different between
angiotensin-converting enzyme insertion/deletion polymorphisms. To our knowledge,
this is the first time that this specific interaction was analyzed during a
volume removal intervention.
PMID- 29949385
TI - Managing Sleep Apnea in Those Who Fail Continuous Positive Airway Pressure.
Dealing with the Invisible Epidemic.
PMID- 29949386
TI - The Impact of Maxillary Advancement on Consonant Proficiency in Patients With
Cleft Lip and Palate, Lay Listeners' Opinion, and Patients' Satisfaction With
Speech.
AB - OBJECTIVE: This study investigates the impact of maxillary advancement (Le Fort I
osteotomy) on consonant proficiency in patients with cleft lip and palate (CLP)
and explores how these patients and lay people perceive their speech 1 year post
Le Fort I osteotomy. DESIGN: Retrospective group study before and after
treatment. PARTICIPANTS: All patients with CLP who had undergone Le Fort I
osteotomy for maxillary retrognathia between 2007 and 2010 at Karolinska
University Hospital, Sweden (n = 21). Six patients were excluded due to
additional malformations and missing data. Two experienced speech and language
pathologists assessed consonant proficiency, and speech accuracy was determined
by lay listeners from pre- and postoperative standardized audio recordings. The
patients' satisfaction with speech postoperatively was collected from medical
records. MAIN OUTCOME MEASURES: Percentage of oral consonants correct and
acoustic analysis of /s/, lay listeners' opinion, and patients' satisfaction with
speech. RESULTS: One year postoperation, 11 of the 15 patients had improved
articulation, especially on the /s/-sound, without speech intervention. The mean
percentage of oral consonants correct before treatment (82%) was significantly
improved later (95%; P > .01). This assessment was supported by the patients'
satisfaction with speech. However, lay listeners' opinion on accuracy was
inconsistent. Length of maxillary advancement or change in occlusion did not
correlate with change in articulation. CONCLUSION: Maxillary advancement
performed to normalize occlusion and facial profile improved consonant
proficiency in patients with CLP 1 year postoperation. Lay listeners' and
patients' perceptions of speech need further exploration.
PMID- 29949387
TI - Nasopharyngeal Dermoids and Cleft Palate.
AB - Nasopharyngeal dermoids associated with cleft palate present as intraoral
protruding masses. Only 5 cases of nasopharyngeal dermoids associated with cleft
palate have been reported in the literature. We are reporting 4 such cases
encountered by us in the last 10 years in our series of 900 cleft palate
surgeries. Imaging studies were done to know the extension of dermoid and to look
for any associated congenital intracranial anomalies. We observed that
nasopharyngeal dermoids are usually nonmalignant and can be easily managed by
complete local excision followed by palatal closure after 6 months.
PMID- 29949388
TI - Recently Described and Clinically Important Entities in Testis Tumors.
AB - CONTEXT: - In 2016 the World Health Organization published a revised
classification of testicular neoplasms based upon advances in understanding their
pathogenesis and molecular biology. The rationale for this revision and
additional clinically relevant observations were the topics of a talk given to
the Houston Society of Clinical Pathologists in April 2017. This paper summarizes
that talk. OBJECTIVE: - To summarize and explain the most important changes to
the classification of testicular neoplasms in the World Health Organization 2016
revision. DATA SOURCES: - Peer-reviewed published literature and contributions by
individuals with expertise in this area that were also reviewed by genitourinary
pathologists. CONCLUSIONS: - Most changes occurred in the germ cell tumor
classification, including replacement of the terms intratubular germ cell
neoplasia unclassified and carcinoma in situ by germ cell neoplasia in situ;
subdivision of the tumors into 2 main categories, those derived from germ cell
neoplasia in situ and those not derived from germ cell neoplasia in situ;
distinction of germ cell neoplasia in situ from germ cells with delayed
maturation and pre-germ cell neoplasia in situ; expansion of the trophoblastic
tumor category to include epithelioid trophoblastic tumor and cystic
trophoblastic tumor; and substitution of spermatocytic tumor for spermatocytic
seminoma and its placement in the non-germ cell neoplasia in situ group. Other
revisions included eliminating sclerosing Sertoli cell tumor as a distinct
entity; the recognition of intratubular hyalinizing Sertoli cell tumor; and
acceptance of the role of undifferentiated gonadal tissue in the pathogenesis of
gonadoblastoma.
PMID- 29949389
TI - Laboratory and Clinical Performance of the ADVIA Centaur Anticyclic Citrullinated
Peptide Assay for Rheumatoid Arthritis Diagnosis.
AB - CONTEXT.-: Anticyclic citrullinated peptide antibodies are important serologic
markers for the diagnosis of rheumatoid arthritis. Several kinds of test reagents
for automated immunoassay systems have been developed and used in recent years.
OBJECTIVE.-: To evaluate the analytic and diagnostic performance of the new ADVIA
Centaur anticyclic citrullinated peptide assay (Siemens Healthineers, Erlangen,
Germany) compared with the Elecsys assay (Roche Diagnostics, Mannheim, Germany).
DESIGN.-: A total of 576 serum samples were collected from subjects, including
156 patients (27%) with rheumatoid arthritis. Precision performance and
analytical measurement range for the ADVIA assay were evaluated. Diagnostic
performance of the 2 assays was compared based on sensitivity, specificity, and
area under the receiver operating characteristic curves. RESULTS.-: The ADVIA
assay showed a within-laboratory imprecision of 3.4% coefficient of variation for
levels of 3.36 and 24.99 U/mL. This assay was demonstrated to be linear from 0.4
to 180.0 U/mL. With default cutoff values, sensitivity and specificity for
diagnosing rheumatoid arthritis were 71.2% and 97.9%, respectively, for the ADVIA
assay and 73.1% and 96.9%, respectively, for the Elecsys assay. With the best
cutoff values from the analyses of the receiver operating characteristic curve,
the sensitivity of the 2 assays was the same at 75.6%. However, the specificity
of the ADVIA assay was 96.4%, whereas that of the Elecsys assay was 94.3%. The
area under the receiver operating characteristic curve value for the ADVIA assay
was 0.867, which was not significantly different from that of the Elecsys assay
(0.865). CONCLUSIONS.-: The ADVIA Centaur anticyclic citrullinated peptide assay
showed good analytic and diagnostic performance in diagnosing rheumatoid
arthritis.
PMID- 29949390
TI - Physical frailty and cognitive impairment is associated with diabetes and
adversely impact functional status and mortality.
AB - OBJECTIVES: We investigated whether there was a higher prevalence of cognitive
impairment (CI) and/or physical frailty (PF) in persons with diabetes compared to
their non-diabetic counterparts, and the individual and combined impact of CI and
PF on functional and mortality outcomes among diabetic older persons. METHOD:
Community-living diabetic and non-diabetic participants (N = 2696) aged 55 and
above were assessed on CI (MMSE) and PF (CHS criteria) status. Among 486 diabetic
persons, we estimated the odds ratio and 95% confidence intervals (OR, 95% CI) of
association of CI and/or PF with prevalent IADL and ADL disability and mortality
from 11 years of follow up. RESULTS: Diabetes was associated with significantly
higher prevalence of CI and/or PF. Adjusted for sex, age, education, smoking,
alcohol intake, physical activity, and BMI, diabetes was associated with higher
prevalence of PF alone (OR = 2.24, 1.16-4.34) and PF with CI (OR = 2.01, 1.12
3.60), but not with CI alone (OR = 1.02, 0.73-1.44). In multivariable analyses of
486 diabetic older adults, compared to non-frail (NF) and cognitive normal (CN),
CI alone was not significantly associated with IADL (OR = 1.06, 0.53-2.10), but
PF alone was associated with considerably higher prevalence of IADL (OR = 6.72,
1.84-24.5). PF with CI was associated with the highest prevalence of IADL (OR =
17.8, 3.66-8.68) and ADL disability (OR = 93.8, 23.6-372.4). Whether singly or in
combination, PF and/or CI were associated with worse hazard (HR) ratio for
mortality outcomes: CI alone (HR = 2.72, 1.48-5.01), PF alone (HR = 4.30, 1.88
9.82) and CI with PF (HR = 8.41, 3.95-17.9). CONCLUSION: Cognitive impairment
and/or physical frailty are powerful prognostic factors identifying people with
diabetes at high risk of mortality.
PMID- 29949391
TI - Increased Megalin Expression in Early Type 2 Diabetes: Role of Insulin Signaling
Pathways.
AB - The megalin/cubilin complex is responsible for the majority of serum protein
reclamation in the proximal tubules. The current study examined if decreases in
their renal expression, along with the albumin recycling protein FcRn, could
account for proteinuria/albuminuria in the Zucker Diabetic Fatty rat model of
type 2 diabetic nephropathy. Immunoblots of renal cortex samples obtained at
worsening disease stages demonstrated no loss in megalin, cubilin, or FcRn, even
when proteinuria was measured. Additionally, early diabetic rats exhibited
significantly increased renal megalin expression when compared to controls
(adjusted p < 0.01). Based on these results, the ability of insulin to increase
megalin was examined in a clonal subpopulation of the Opossum Kidney proximal
tubule cell line. Insulin treatments (24 hours, 100 nM) under high glucose
conditions significantly increased megalin protein (p < 0.0001), mRNA (p <
0.0001), and albumin endocytosis. The effect on megalin expression was prevented
with inhibitors against key effectors of insulin intracellular signaling:
phosphatidylinositide 3-kinase and Akt. Studies using rapamycin to inhibit the
mechanistic target of rapamycin complex 1 (mTORC1) resulted in a loss of insulin
induced megalin expression. However, subsequent evaluation demonstrated these
effects were independent of initial mTORC1 suppression. The presented results
provide insight into the expression of megalin, cubilin, and FcRn in type 2
diabetic nephropathy, which may be impacted by elevated insulin and glucose.
Furthermore, proximal tubule endocytic activity in early diabetics may be
enhanced, a process that could have a significant role in proteinuria-induced
renal damage.
PMID- 29949393
TI - A central role for Toll-like 4 receptors in interstitial cystitis?
PMID- 29949392
TI - Rodent models of AKI-CKD transition.
AB - Acute kidney injury (AKI) is a contributing factor in the development and
progression of chronic kidney disease (CKD). Despite rapid progresses, the
mechanism underlying AKI-CKD transition remains largely unclear. Animal models
recapitulating this process are crucial to the research of the pathophysiology of
AKI-CKD transition and the development of effective therapeutics. In this review,
we present the commonly used rodent models of AKI-CKD transition, including
bilateral ischemia-reperfusion injury (IRI), unilateral IRI, unilateral IRI with
contralateral nephrectomy, multiple episodes of IRI, and repeated treatment of
low-dose cisplatin, diphtheria toxin, aristolochic acid, or folic acid. The main
merits and pitfalls of these models are also discussed. This review provides
helpful information for establishing reliable and clinically relevant models for
studying post-AKI development of chronic renal pathologies and the progression to
CKD.
PMID- 29949394
TI - Diagnosis of drug causality in non-immediate drug hypersensitivity in children.
PMID- 29949395
TI - Interim Futility Monitoring Assessing Immune Therapies With a Potentially Delayed
Treatment Effect.
AB - Purpose Introduction of new immune therapies that may have a delayed beneficial
effect necessitates re-evaluation of traditional clinical trial designs in
oncology. A key design feature of randomized trials is interim futility
monitoring, which allows stopping early if the accruing data convincingly
demonstrate that the experimental treatment is detrimental or is unlikely to be
shown superior to the standard treatment. The appropriateness of futility
monitoring is frequently questioned when the effect of the experimental treatment
may be delayed (eg, in trials of many immune agents). We examine the advisability
of using futility monitoring when there is potential for a delayed treatment
effect and make recommendations concerning its use. Methods We evaluated the loss
of statistical power when using some common futility interim monitoring rules and
a new proposed conservative rule via simulation under varying amounts of
treatment-effect delay and varying accrual periods. We also considered scenarios
where the experimental treatment starts out being worse than the standard
treatment but ends up being better, as may sometimes be the case when an immune
therapy is compared with an active standard therapy. Results Some standard
methods of futility monitoring can result in an unacceptable loss of power when
there is a delayed treatment effect, especially if the accrual period is rapid or
the experimental treatment is initially worse. The proposed conservative futility
rule has a negligible loss of power in the situations considered. Conclusion
Although care must be taken with the choice of futility monitoring when there is
a delayed treatment effect, inclusion of appropriate rules can reduce the
exposure of patients to ineffective therapies without reducing the probability of
correctly identifying effective treatments.
PMID- 29949396
TI - Design, Fabrication, and Testing of a Microfluidic Device for Thermotaxis and
Chemotaxis Assays of Sperm.
AB - Infertile couples needing assisted reproduction are increasing, so a fundamental
understanding of motile sperm migration is required. This paper presents an
advanced microfluidic device for sperm motion analysis utilizing chemotaxis and
thermotaxis simultaneously for the first time. The proposed device is a
transparent polydimethylsiloxane- and glass-based microfluidic chip system
providing a low-cost, useful, and disposable platform for sperm analysis. The
concentration gradient of the chemoattractant (acetylcholine) and the temperature
difference are formed along the microchannel. The temperature gradient is
generated and controlled by a microheater and microsensor. Thermotactic and
chemotactic responses of mouse sperm were examined using the proposed device.
Experimental results show that motile mouse sperm are attracted more sensitively
under integrated conditions of chemotaxis and thermotaxis rather than individual
conditions of chemotaxis and thermotaxis. This sperm analysis device is expected
to be a useful tool for the study of mammalian sperm migration and the
improvement of artificial insemination techniques.
PMID- 29949397
TI - 3D printed upper limb prosthetics.
AB - INTRODUCTION: In the last 15 years, the market for prosthetic arms and hands has
shifted toward systems with greater degrees of actuation. There has also been a
progressive use of emerging technologies to overcome hardware design challenges.
Moreover, the proliferation of rapid prototyping has resulted in applications in
the prosthetic market. Even though there are concerns on robustness and wide-user
acceptance, the affordable and customizable solution offered by rapid
prototyping, combined with the possibility for easy maintenance and repair, is
very attractive for prosthesis design. Areas covered: Functional layouts for
multi-articulated, dexterous 3D printed hands and sockets are freely available,
with many patients using them at home. We provide an overview of the current
solutions, compare their features, and discuss their potential impact on the
field of prosthetics. Expert commentary: The high level of low-cost customization
is an appealing concept, but this comes with challenges not yet systematically
addressed; such challenges include durability, sufficient grip strength,
reproducibility, and general appeal to the wide range of users. The introduction
of new printable materials could assist in overcoming some of these issues, but
present an added risk of compromising the low cost and wide availability.
PMID- 29949398
TI - Multiple-Point Evaluation Algorithms for Enhanced Precision of Pathogen-Specific
Cerebrospinal Fluid/Serum Antibody Index Calculation.
AB - The determination of pathogen-specific antibody indices (AIs) of CSF and serum is
an essential cornerstone in assessing neurological diseases and demands reliable
high precision. Various companies provide ELISA kits for the detection of
respective antibody concentrations and base AI calculation on a single CSF/serum
pair of optical densities (ODs), combined with selection rules. The remainder of
OD measurements is not used. There is no averaging of measurement errors and
result stabilization. OD data from Siemens Enzygnost ELISA measurements of 2012
2016 proficiency survey samples for measles/rubella/varicella zoster/herpes
simplex virus (MRZH) reaction (INSTAND e.V.) were reanalyzed. Several reference
methods for calculating Q values from ODs using multiple-point evaluation are
described. The methods are based on the alpha method and the four-parameter
logistic (4PL) equation. Statistical analysis shows standard deviations of
relative AI differences from AI target values to be significantly lower if
derived from multiple-point evaluation instead of single-pair evaluation. Thus,
the virus-averaged hit rate of a 10% target AI environment can be improved from
49% up to 69%. Waiving the usage of a standard curve in favor of parameter
fitting significantly improves calculational precision for Siemens Enzygnost
assays. Patient safety, diagnostic assay costs, and laboratory effectiveness
might be improved for other test distributors as well.
PMID- 29949399
TI - Ustekinumab for the treatment of psoriasis and psoriatic arthritis: a drug
evaluation and literature review.
AB - INTRODUCTION: Psoriasis (PsO) is an inflammatory disorder characterized by
proliferation of keratinocytes, and it may be associated with a systemic
inflammatory articular disorder, psoriatic arthritis (PsA). The presentations of
PsO and PsA are heterogeneous, and our understanding of pathogenesis has led to a
better understanding of the role of the interleukin (IL)-23/T-helper 17 (Th17)
axis. Areas covered: Ustekinumab is a monoclonal antibody against IL-12 and IL
23. The pathogenesis of PsO and PsA is a multifactorial process involving
genetic, environmental, and lifestyle factors. IL-23 signaling and activation of
Th17 cells leads to a self-perpetuating inflammatory loop resulting in continuous
keratinocyte proliferation and synovitis. Treatment options are varied, ranging
from topical therapy to injection of targeted biologic disease-modifying
antirheumatic drugs (bDMARDs). Evidence on the use of ustekinumab in the
management of PsO is strong, but it is not as impressive in management of PsA.
Expert opinion: IL-12/23 inhibition appears to be a good first-line option for
plaque PsO, but efficacy in PsA does not compare favorably to IL-17 inhibition.
In general, poorer responses to therapy with any bDMARD in PsA cohorts highlight
psoriatic disease heterogeneity. Until new knowledge can remedy the failure of
monotherapy, synergistic methods may have to be explored, including combination
biologic therapy.
PMID- 29949400
TI - High Prevalence of Mycoplasma and Eimeria Species in Free-Ranging Eastern Wild
Turkeys ( Meleagris gallopavo silvestris) in Ontario, Canada.
AB - Following extirpation from Ontario, Canada, in the early 1900s, Eastern Wild
Turkeys (EWTs; Meleagris gallopavo silvestris) were successfully reintroduced to
the province in 1984. Despite the subsequent establishment of robust populations
and biannual hunting seasons, data on the circulation of potential pathogens in
these birds are lacking. Similarly, the interface between EWTs and poultry is
poorly understood and includes possible bidirectional pathogen transmission via
direct or indirect contact. Mycoplasma and Eimeria spp. are potential pathogens
in Galliformes, and our objective was to determine their prevalence and
distribution in Ontario EWTs. During the 2015 spring hunting season (April and
May), oropharyngeal swabs from 147 hunter-harvested and five opportunistically
collected EWTs from southern Ontario were cultured for Mycoplasma spp. The
intestinal or cloacal contents of 107 of these birds and an additional 24
opportunistically and biologist-collected EWTs were analyzed for Eimeria spp.
using PCR or fecal flotation. At least one Mycoplasma spp. was isolated from
98.7% (150/152) of EWTs, with six species identified. Mycoplasma gallopavonis was
identified most commonly in 96.7% (147/152), followed by Mycoplasma gallinaceum
in 23.7% (36/152). Potential poultry pathogens ( Mycoplasma meleagridis,
Mycoplasma iowae, and Mycoplasma synoviae) were isolated from swabs of five
(3.3%) EWTs. Coinfections with up to three Mycoplasma spp. were detected in 36.8%
(56/152) of EWTs. Most EWTs tested positive for Eimeria spp. oocysts (75.6%;
99/131). A subset of positive samples ( n=16) were characterized by PCR, which
detected the following species: Eimeria meleagrimitis (93.8%), Eimeria adenoeides
(93.8%), Eimeria gallopavonis (56.3%), and Eimeria meleagridis (12.5%). The
majority (93.8%) of these samples were positive for more than one Eimeria spp. We
showed that numerous, mostly nonpathogenic Mycoplasma and Eimeria spp. circulate
in EWTs across southern Ontario, and this helped to establish baseline
information for comparison with future surveillance and monitoring.
PMID- 29949401
TI - Protein phosphatase 2A is crucial for sarcomere organization in Caenorhabditis
elegans striated muscle.
AB - Protein phosphatase 2A (PP2A) is a heterotrimer composed of single catalytic and
scaffolding subunits and one of several possible regulatory subunits. We
identified PPTR-2, a regulatory subunit of PP2A, as a binding partner for the
giant muscle protein UNC-89 (obscurin) in Caenorhabditis elegans. PPTR-2 is
required for sarcomere organization when its paralogue, PPTR-1, is deficient.
PPTR-2 localizes to the sarcomere at dense bodies and M-lines, colocalizing with
UNC-89 at M-lines. PP2A components in C. elegans include one catalytic subunit
LET-92, one scaffolding subunit (PAA-1), and five regulatory subunits (SUR-6,
PPTR-1, PPTR-2, RSA-1, and CASH-1). In adult muscle, loss of function in any of
these subunits results in sarcomere disorganization. rsa-1 mutants show an
interesting phenotype: one of the two myosin heavy chains, MHC A, localizes as
closely spaced double lines rather than single lines. This "double line"
phenotype is found in rare missense mutants of the head domain of MHC B myosin,
such as unc-54(s74). Analysis of phosphoproteins in the unc-54(s74) mutant
revealed two additional phosphoserines in the nonhelical tailpiece of MHC A.
Antibodies localize PPTR-1, PAA-1, and SUR-6 to I-bands and RSA-1 to M-lines and
I-bands. Therefore, PP2A localizes to sarcomeres and functions in the assembly or
maintenance of sarcomeres.
PMID- 29949402
TI - Olfactomedin 4 contributes to hydrogen peroxide-induced NADPH oxidase activation
and apoptosis in mouse neutrophils.
AB - Neutrophils increase production of reactive oxygen species, including superoxide,
hydrogen peroxide (H2O2), and hydroxyl radical, to destroy invading
microorganisms under pathological conditions. Conversely, oxidative stress
conditions, such as the presence of H2O2, induce neutrophil apoptosis, which
helps to remove neutrophils after inflammation. However, the detailed molecular
mechanisms that are involved in the latter process have not been elucidated. In
this study, we investigated the potential role of olfactomedin 4 (Olfm4) in H2O2
induced superoxide production and apoptosis in mouse neutrophils. We have
demonstrated that Olfm4 is not required for maximal-dosage PMA- and Escherichia
coli bacteria-induced superoxide production, but Olfm4 contributes to suboptimal
dosage PMA- and H2O2-induced superoxide production. Using an NADPH oxidase
inhibitor and gp91phox-deficient mouse neutrophils, we found that NAPDH oxidase
was required for PMA-stimulated superoxide production and that Olfm4 mediated
H2O2-induced superoxide production through NADPH oxidase, in mouse neutrophils.
We have shown that neutrophils from Olfm4-deficient mice exhibited reduced H2O2
induced apoptosis compared with neutrophils from wild-type mice. We also
demonstrated that neutrophils from Olfm4-deficient mice exhibited reduced H2O2
stimulated mitochondrial damage and membrane permeability, and as well as reduced
caspase-3 and caspase-9 activity, compared with neutrophils from wild-type mice.
Moreover, the cytoplasmic translocation of the proapoptotic mitochondrial
proteins Omi/HtrA2 and Smac/DIABLO in response to H2O2 was reduced in neutrophils
from Olfm4-deficient mice compared with neutrophils from wild-type mice. Our
study demonstrates that Olfm4 contributes to H2O2-induced NADPH oxidase
activation and apoptosis in mouse neutrophils. Olfactomedin 4 might prove to be a
potential target for future studies on inflammatory neutrophil biology and for
inflammatory disease treatment.
PMID- 29949403
TI - Effect of Tim23 knockdown in vivo on mitochondrial protein import and retrograde
signaling to the UPRmt in muscle.
AB - The mitochondrial unfolded protein response (UPRmt) is a protein quality control
mechanism that strives to achieve proteostasis in the face of misfolded proteins.
Because of the reliance of mitochondria on both the nuclear and mitochondrial
genomes, a perturbation of the coordination of these genomes results in a
mitonuclear imbalance in which holoenzymes are unable to assume mature
stoichiometry and thereby activates the UPRmt. Thus, we sought to perturb this
genomic coordination by using a systemic antisense oligonucleotide (in vivo
morpholino) targeted to translocase of the inner membrane channel subunit 23
(Tim23), the major channel of the inner membrane. This resulted in a 40%
reduction in Tim23 protein content, a 32% decrease in matrix-destined protein
import, and a trend to elevate reactive oxygen species (ROS) emission under
maximal respiration conditions. This import defect activated the C/EBP homologous
protein (CHOP) branch of the UPRmt, as evident from increases in caseinolytic
mitochondrial matrix peptidase proteolytic subunit (ClpP) and chaperonin 10
(cpn10) but not the activating transcription factor 5 (ATF5) arm. Thus, in the
face of proteotoxic stress, CHOP and ATF5 could be activated independently to
regain proteostasis. Our second aim was to investigate the role of
proteolytically derived peptides in mediating retrograde signaling. Peptides
released from the mitochondrion following basal proteolysis were isolated and
incubated with import reactions. Dose- and time-dependent effect of peptides on
protein import was observed. Our data suggest that mitochondrial proteolytic
byproducts exert an inhibitory effect on protein import, possibly to reduce
excessive protein import as a potential negative feedback mechanism. The
inhibition of import into the organelle also serves a retrograde function,
possibly via ROS emission, to modify nuclear gene expression and ultimately
improve folding capacity.
PMID- 29949405
TI - Choroid plexus glutathione peroxidases are instrumental in protecting the brain
fluid environment from hydroperoxides during postnatal development.
AB - Hydrogen peroxide, released at low physiological concentration, is involved in
different cell signaling pathways during brain development. When released at
supraphysiological concentrations in brain fluids following an inflammatory,
hypoxic, or toxic stress, it can initiate lipid peroxidation, protein, and
nucleic acid damage and contribute to long-term neurological impairment
associated with perinatal diseases. We found high glutathione peroxidase and
glutathione reductase enzymatic activities in both lateral and fourth ventricle
choroid plexus tissue isolated from developing rats, in comparison to the
cerebral cortex and liver. Consistent with these, a high protein expression of
glutathione peroxidases 1 and 4 was observed in choroid plexus epithelial cells,
which form the blood-cerebrospinal fluid barrier. Live choroid plexuses isolated
from newborn rats were highly efficient in detoxifying H2O2 from mock
cerebrospinal fluid, illustrating the capacity of the choroid plexuses to control
H2O2 concentration in the ventricular system of the brain. We used a
differentiated cellular model of the blood-cerebrospinal fluid barrier coupled to
kinetic and inhibition analyses to show that glutathione peroxidases are more
potent than catalase to detoxify extracellular H2O2 at concentrations up to 250
uM. The choroidal cells also formed an enzymatic barrier preventing blood-borne
hydroperoxides to reach the cerebrospinal fluid. These data point out the choroid
plexuses as key structures in the control of hydroperoxide levels in the cerebral
fluid environment during development, at a time when the protective glial cell
network is still immature. Glutathione peroxidases are the main effectors of this
choroidal hydroperoxide inactivation.
PMID- 29949406
TI - Transgelin induces dysfunction of fetal endothelial colony-forming cells from
gestational diabetic pregnancies.
AB - Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to
future health complications including hypertension and cardiovascular disease. A
key mechanism by which these complications occur is through the functional
impairment of vascular progenitor cells, including endothelial colony-forming
cells (ECFCs). Previously, we showed that fetal ECFCs exposed to GDM have
decreased vasculogenic potential and altered gene expression. In this study, we
evaluate whether transgelin (TAGLN), which is increased in GDM-exposed ECFCs,
contributes to vasculogenic dysfunction. TAGLN is an actin-binding protein
involved in the regulation of cytoskeletal rearrangement. We hypothesized that
increased TAGLN expression in GDM-exposed fetal ECFCs decreases network formation
by impairing cytoskeletal rearrangement resulting in reduced cell migration. To
determine if TAGLN is required and/or sufficient to impair ECFC network
formation, TAGLN was reduced and overexpressed in ECFCs from GDM and
uncomplicated pregnancies, respectively. Decreasing TAGLN expression in GDM
exposed ECFCs improved network formation and stability as well as increased
migration. In contrast, overexpressing TAGLN in ECFCs from uncomplicated
pregnancies decreased network formation, network stability, migration, and
alignment to laminar flow. Overall, these data suggest that increased TAGLN
likely contributes to the vasculogenic dysfunction observed in GDM-exposed ECFCs,
as it impairs ECFC migration, cell alignment, and network formation. Identifying
the molecular mechanisms underlying fetal ECFC dysfunction following GDM exposure
is key to ascertain mechanistically the basis for cardiovascular disease
predisposition later in life.
PMID- 29949404
TI - Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and
transporters for vascular protection.
AB - The blood-brain barrier (BBB) is a physical and biochemical barrier that
precisely controls cerebral homeostasis. It also plays a central role in the
regulation of blood-to-brain flux of endogenous and exogenous xenobiotics and
associated metabolites. This is accomplished by molecular characteristics of
brain microvessel endothelial cells such as tight junction protein complexes and
functional expression of influx and efflux transporters. One of the
pathophysiological features of ischemic stroke is disruption of the BBB, which
significantly contributes to development of brain injury and subsequent
neurological impairment. Biochemical characteristics of BBB damage include
decreased expression and altered organization of tight junction constituent
proteins as well as modulation of functional expression of endogenous BBB
transporters. Therefore, there is a critical need for development of novel
therapeutic strategies that can protect against BBB dysfunction (i.e., vascular
protection) in the setting of ischemic stroke. Such strategies include targeting
tight junctions to ensure that they maintain their correct structure or targeting
transporters to control flux of physiological substrates for protection of
endothelial homeostasis. In this review, we will describe the pathophysiological
mechanisms in cerebral microvascular endothelial cells that lead to BBB
dysfunction following onset of stroke. Additionally, we will utilize this state
of-the-art knowledge to provide insights on novel pharmacological strategies that
can be developed to confer BBB protection in the setting of ischemic stroke.
PMID- 29949407
TI - Alterations in dietary sodium intake affect cardiovagal baroreflex sensitivity.
AB - High dietary sodium intake has been linked to alterations in neurally mediated
cardiovascular function, but the effects of high sodium on cardiovagal baroreflex
sensitivity (cBRS) in healthy adults are unknown. The purpose of this study was
to determine whether high dietary sodium alters cBRS and heart rate variability
(HRV) and whether acute intravenous sodium loading similarly alters cBRS and HRV.
High dietary sodium (300 mmol/day, 7 days) was compared with low dietary sodium
(20 mmol/day, 7 days; randomized) in 14 participants (38 +/- 4 yr old, 23 +/- 1
kg/m2 body mass index, 7 women). Acute sodium loading was achieved via a 23-min
intravenous hypertonic saline infusion (HSI) in 14 participants (22 +/- 1 yr old,
23 +/- 1 kg/m2 body mass index, 7 women). During both protocols, participants
were supine for 5 min during measurement of beat-to-beat blood pressure
(photoplethysmography) and R-R interval (ECG). cBRS was evaluated using the
sequence method. Root mean square of successive differences in R-R interval
(RMSSD) was used as an index of HRV. Serum sodium (137.4 +/- 0.7 vs. 139.9 +/-
0.5 meq/l, P < 0.05), plasma osmolality (285 +/- 1 vs. 289 +/- 1 mosmol/kgH2O, P
< 0.05), cBRS (18 +/- 2 vs. 26 +/- 3 ms/mmHg, P < 0.05), and RMSSD (62 +/- 6 vs.
79 +/- 10 ms, P < 0.05) were increased following high-sodium diet intake compared
with low-sodium diet intake. HSI increased serum sodium (138.1 +/- 0.4 vs. 141.1
+/- 0.5 meq/l, P < 0.05) and plasma osmolality (286 +/- 1 vs. 290 +/- 1
mosmol/kgH2O, P < 0.05) but did not change cBRS (26 +/- 5 vs. 25 +/- 3 ms/mmHg, P
= 0.73) and RMSSD (63 +/- 9 vs. 63 +/- 8 ms, P = 0.99). These data suggest that
alterations in dietary sodium intake alter cBRS and HRV but that acute
intravenous sodium loading does not alter these indexes of autonomic
cardiovascular regulation.
PMID- 29949408
TI - Absent increase in vertebral artery blood flow during l-arginine infusion in
hypertensive men.
AB - Endothelial dysfunction is observed in the peripheral vasculature of hypertensive
patients, but it is unclear how the cerebral circulation is affected. More
specifically, little is known about the impact of human hypertension on vertebral
artery (VA) endothelial function. This study evaluated whether the endothelial
function of the VA is impaired in hypertensive men. For 13 male hypertensive
subjects (46 +/- 3 yr) and eight age-matched male controls (46 +/- 4 yr), blood
pressure (BP; photoplethysmography), VA, and common carotid (CC) blood flow
(duplex ultrasound) were determined at rest and during 30 min of intravenous l
arginine (30 g; a precursor of nitric oxide) or isotonic saline infusion.
Controls and hypertensive subjects demonstrated a similar resting CC (601 +/- 30
vs. controls 570 +/- 43 ml/min; P = 0.529) and VA blood flow (119 +/- 11 vs.
controls 112 +/- 9 ml/min; P = 0.878). During administration of l-arginine, CC
blood flow increased similarly between groups (hypertensive 12 +/- 3%, controls
13 +/- 2%; P = 0.920). In contrast, the increase in VA blood flow was nonexistent
in the hypertensive subjects (0.8 +/- 3% vs. controls: 16 +/- 4%; P = 0.015) with
no significant change in BP. Both CC and VA flow returned to near-resting values
within 30 min after the infusion, and for four hypertensive subjects and three
controls, time-control experiments using 0.9% saline did not affect VA or CC
blood flow significantly. The results demonstrate endothelial dysfunction in the
posterior cerebral circulation of middle-aged hypertensive men.
PMID- 29949409
TI - Exercise cardiac magnetic resonance imaging: a feasibility study and meta
analysis.
AB - Cardiac stress testing improves detection and risk assessment of heart disease.
Magnetic resonance imaging (MRI) is the clinical gold-standard for assessing
cardiac morphology and function at rest; however, exercise MRI has not been
widely adapted for cardiac assessment because of imaging and device limitations.
Commercially available magnetic resonance ergometers, together with improved
imaging sequences, have overcome many previous limitations, making cardiac stress
MRI more feasible. Here, we aimed to demonstrate clinical feasibility and
establish the normative, healthy response to supine exercise MRI. Eight young,
healthy subjects underwent rest and exercise cinematic imaging to measure left
ventricular volumes and ejection fraction. To establish the normative, healthy
response to exercise MRI we performed a comprehensive literature review and meta
analysis of existing exercise cardiac MRI studies. Results were pooled using a
random effects model to define the left ventricular ejection fraction, end
diastolic, end-systolic, and stroke volume responses. Our proof-of-concept data
showed a marked increase in cardiac index with exercise, secondary to an increase
in both heart rate and stroke volume. The change in stroke volume was driven by a
reduction in end-systolic volume, with no change in end-diastolic volume. These
findings were entirely consistent with 17 previous exercise MRI studies (226
individual records), despite differences in imaging approach, ergometer, or
exercise type. Taken together, the data herein demonstrate that exercise cardiac
MRI is clinically feasible, using commercially available exercise equipment and
vendor-provided product sequences and establish the normative, healthy response
to exercise MRI.
PMID- 29949411
TI - Purinergic plasticity within petrosal neurons in hypertension.
AB - The carotid bodies are peripheral chemoreceptors and contribute to the
homeostatic maintenance of arterial levels of O2, CO2 and [H+]. They have
attracted much clinical interest recently because of the realisation that
aberrant signalling in these organs is associated with several pathologies
including hypertension. Herein, we describe data suggesting that sympathetic
overactivity in neurogenic hypertension is, at least in part, dependent on
carotid body tonicity and hyperreflexia that is related to changes in the
electrophysiological properties of chemoreceptive petrosal neurons. We present
results showing critical roles for both ATP levels in the carotid bodies and
expression of P2X3 receptors in petrosal chemoreceptive, but not baroreceptive,
terminals in the aetiology of carotid body tonicity and hyperreflexia. We discuss
mechanisms that may underlie the changes in electrophysiological properties and
P2X3 receptor expression in chemoreceptive petrosal neurons, as well as factors
affecting ATP release by cells within the carotid bodies. Our findings support
the notion of targeting the carotid bodies to reduce sympathetic outflow and
arterial pressure, emphasizing the potential clinical importance of modulating
purinergic transmission to treat pathologies associated with carotid body
dysfunction, but, importantly, sparing physiological chemoreflex function.
PMID- 29949412
TI - Imaging the Postoperative Knee Meniscus: An Evidence-Based Review.
AB - OBJECTIVE: Unenhanced MRI, indirect MR arthrography, direct MR arthrography, and
CT arthrography are each currently used to evaluate patients with recurrent knee
pain after meniscus surgery. The purpose of this study is to review the evidence
for the use of these examinations in patients with suspected recurrent meniscus
tear. CONCLUSION: Direct and indirect MR arthrography are superior to
conventional MRI for the assessment of the postoperative meniscus after meniscus
repair or partial meniscectomy involving more than 25% of the meniscus.
PMID- 29949410
TI - Oleoylethanolamide modulates glucagon-like peptide-1 receptor agonist signaling
and enhances exendin-4-mediated weight loss in obese mice.
AB - Long-acting glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists (GLP-1RA),
such as exendin-4 (Ex4), promote weight loss. On the basis of a newly discovered
interaction between GLP-1 and oleoylethanolamide (OEA), we tested whether OEA
enhances GLP-1RA-mediated anorectic signaling and weight loss. We analyzed the
effect of GLP-1+OEA and Ex4+OEA on canonical GLP-1R signaling and other
proteins/pathways that contribute to the hypophagic action of GLP-1RA (AMPK, Akt,
mTOR, and glycolysis). We demonstrate that OEA enhances canonical GLP-1R
signaling when combined with GLP-1 but not with Ex4. GLP-1 and Ex4 promote
phosphorylation of mTOR pathway components, but OEA does not enhance this effect.
OEA synergistically enhanced GLP-1- and Ex4-stimulated glycolysis but did not
augment the hypophagic action of GLP-1 or Ex4 in lean or diet-induced obese (DIO)
mice. However, the combination of Ex4+OEA promoted greater weight loss in DIO
mice than Ex4 or OEA alone during a 7-day treatment. This was due in part to
transient hypophagia and increased energy expenditure, phenotypes also observed
in Ex4-treated DIO mice. Thus, OEA augments specific GLP-1RA-stimulated signaling
but appears to work in parallel with Ex4 to promote weight loss in DIO mice.
Elucidating cooperative mechanisms underlying Ex4+OEA-mediated weight loss could,
therefore, be leveraged toward more effective obesity therapies.
PMID- 29949413
TI - Clinical PET/MRI: 2018 Update.
AB - OBJECTIVE: The purpose of this article is to provide an update on clinical
PET/MRI, including current and developing clinical indications and technical
developments. CONCLUSION: PET/MRI is evolving rapidly, transitioning from a
predominant research focus to exciting clinical practice. Key technical obstacles
have been overcome, and further technical advances promise to herald significant
advancements in image quality. Further optimization of protocols to address
challenges posed by this hybrid modality will ensure the long-term success of
PET/MRI.
PMID- 29949414
TI - Evaluation of Unroofed Coronary Sinus Syndrome Using Cardiovascular CT
Angiography: An Observational Study.
AB - OBJECTIVE: The purpose of this study was to determine the prevalence of unroofed
coronary sinus (CS) syndrome at a tertiary hospital and analyze the clinical
information, cardiovascular CT angiography (CCTA) imaging findings, associated
anomalies, and surgical treatment of the identified cases. MATERIALS AND METHODS:
We retrospectively searched the database of a tertiary hospital for cases of
unroofed CS syndrome among patients who underwent CCTA for known or suspected
congenital heart disease. After the prevalence of unroofed CS syndrome was
determined, CCTA findings, associated cardiovascular abnormalities, presence or
absence of airway compression, clinical information, and surgical outcome were
recorded. RESULTS: A total of 23 patients with unroofed CS syndrome were
identified, with the syndrome therefore having a prevalence of 0.36% among
patients with congenital heart disease who underwent CCTA. The diagnostic
accuracy of CCTA for unroofed CS syndrome was 100%, whereas that of
echocardiography was 69%. Type I unroofed CS syndrome was the most commonly noted
type (52% of patients). All 23 patients had associated cardiovascular anomalies,
including persistent left superior vena cava (65% of patients) and atrial septal
defect (65%). Surgery was performed for 70% of patients because of cardiovascular
anomalies. Seven patients (30%) had associated secondary airway compression but
did not require surgical correction. CONCLUSION: At our institution, the
prevalence of unroofed CS syndrome was 0.36% among patients with congenital heart
disease who underwent CCTA. CCTA has excellent diagnostic performance,
delineating different subtypes of unroofed CS syndrome and associated
cardiovascular planning for treatment of unroofed CS syndrome abnormalities,
improving clinical decision making, and permitting preoperative planning for
treatment of unroofed CS syndrome.
PMID- 29949415
TI - PET/CT of Dementia.
AB - OBJECTIVE: In this article, we review the literature on PET/CT in the management
of dementia, present evidence for best clinical practices, and discuss recent
advances in the field. CONCLUSION: Standard-of-care imaging for dementia includes
CT and MRI, primarily for excluding vascular lesions or masses, detecting
atrophy, and monitoring disease severity. PET/CT is a powerful functional
modality that can differentiate dementia types and influence management. Fluorine
18-FDG PET/CT reveals the spatial pattern of glucose metabolism in the brain.
More recently, radiotracers for PET have been developed that bind to amyloid
protein, tau protein, and neuroinflammatory markers.
PMID- 29949416
TI - Neuroendocrine Tumor Therapy: 177Lu-DOTATATE.
AB - OBJECTIVE: The purposes of this article are to increase understanding of the
concepts of theranostics and peptide receptor radionuclide therapy (PRRT) as they
apply to neuroendocrine tumors (NETs); review the key 1, 2, and 3 clinical trial
data leading to the approval of 177Lu-tetraazacyclododecanetetraacetic acid
octreotide (177Lu-DOTATATE); and foster understanding of the practical aspects
and future directions of PRRT for NETs. CONCLUSION: In January 2018, 177Lu
DOTATATE therapy was approved in the United States (previously approved in Europe
in September 2017) for adult patients with somatostatin receptor-positive
gastroenteropancreatic neuroendocrine tumors, including those of the foregut,
midgut, and hindgut. The results of the phase 3 Neuroendocrine Tumors Therapy
(NETTER-1) trial show favorable outcomes with respect to the primary endpoint of
progression-free survival and a host of secondary objectives, including overall
survival, objective response rate, and quality of life measures. Patient
selection is based on a number of specific factors and should be sequenced
carefully with respect to other available therapies, ideally in multidisciplinary
cancer conferences. Establishing the therapy at a new institution can be somewhat
involved, but once it is established, the therapy is fairly straightforward to
administer and is well tolerated with limited side-effects and toxicity. A number
of approaches and issues are still to be worked out, and this therapy will
continue to be studied and optimized.
PMID- 29949417
TI - Postoperative Imaging of the Ankle.
AB - OBJECTIVE: The purpose of this article is to review imaging after commonly
encountered surgical interventions of the ligaments, tendons, and soft tissues
around the ankle. Intraoperative images, when available, are provided to improve
conceptual understanding of these complex procedures. CONCLUSION: Surgical
interventions in the ankle are becoming more prevalent with increasing athletic
demands and emerging focus on techniques for prevention of joint injury.
Knowledge of the surgical techniques, imaging appearances, and complications in
the postoperative ankle is necessary for the accurate diagnosis of postoperative
complications and for optimal patient care.
PMID- 29949418
TI - Utility of Intermediate-Delay Washout CT Images for Differentiation of Malignant
and Benign Adrenal Lesions: A Multivariate Analysis.
AB - OBJECTIVE: The objective of this study was to identify features that impact the
diagnostic performance of intermediate-delay washout CT for distinguishing
malignant from benign adrenal lesions. MATERIALS AND METHODS: This retrospective
study evaluated 127 pathologically proven adrenal lesions (82 malignant, 45
benign) in 126 patients who had undergone portal venous phase and intermediate
delay washout CT (1-3 minutes after portal venous phase) with or without
unenhanced images. Unenhanced images were available for 103 lesions.
Quantitatively, lesion CT attenuation on unenhanced (UA) and delayed (DL) images,
absolute and relative percentage of enhancement washout (APEW and RPEW,
respectively), descriptive CT features (lesion size, margin characteristics,
heterogeneity or homogeneity, fat, calcification), patient demographics, and
medical history were evaluated for association with lesion status using multiple
logistic regression with stepwise model selection. Area under the ROC curve (Az)
was calculated from both univariate and multivariate analyses. The predictive
diagnostic performance of multivariate evaluations was ascertained through cross
validation. RESULTS: Az for DL, APEW, RPEW, and UA was 0.751, 0.795, 0.829, and
0.839, respectively. Multivariate analyses yielded the following significant CT
quantitative features and associated Az when combined: RPEW and DL (Az = 0.861)
when unenhanced images were not available and APEW and UA (Az = 0.889) when
unenhanced images were available. Patient demographics and presence of a prior
malignancy were additional significant factors, increasing Az to 0.903 and 0.927,
respectively. The combined predictive classifier, without and with UA available,
yielded 85.7% and 87.3% accuracies with cross-validation, respectively.
CONCLUSION: When appropriately combined with other CT features, washout derived
from intermediate-delay CT with or without additional clinical data has potential
utility in differentiating malignant from benign adrenal lesions.
PMID- 29949419
TI - Imaging Prostate Cancer With Prostate-Specific Membrane Antigen PET/CT and
PET/MRI: Current and Future Applications.
AB - OBJECTIVE: The purpose of this article is to describe the large number of
radiotracers being evaluated for prostate-specific membrane antigen (PSMA) PET,
which is becoming a central tool in the staging of prostate cancer. CONCLUSION:
PSMA PET is a highly promising modality for the staging of prostate cancer
because of its higher detection rate compared with that of conventional imaging.
Both PET/CT and PET/MRI offer benefits with PSMA radiotracers, and PSMA PET
findings frequently lead to changes in management. It is imperative that
subsequent treatment changes be evaluated to show improved outcomes. PSMA PET
also has potential applications, including patient selection for PSMA-based
radioligand therapy and evaluation of treatment response.
PMID- 29949420
TI - Evaluating Lens Dose Reduction in Pediatric Neuroradiology Examinations Using
Automated Kilovoltage Selection Software.
AB - OBJECTIVE: The purpose of this study is to evaluate the potential of an automated
kilo-voltage selection software for the reduction of lens dose in pediatric CT
scans. MATERIALS AND METHODS: Two metal oxide semiconductor field effect
transistor (MOSFET) detectors measured the lens dose in two anthropomorphic 1-
and 5-year-old phantoms. These phantoms were scanned using a clinical pediatric
brain protocol at 120 kVp as a control with the MDCT scanner. Scans were then
repeated using automated kilovoltage software. The automated kilovoltage was set
to operate at tube potentials of 120, 110, and 100 kVp. Dose savings were
compared with the average lens dose of both eyes between automated kilovoltage
and the control setting. Image quality was studied by contrast-to-noise ratios
(CNRs) for each setting. RESULTS: The mean (+/- SD) lens dose from the routine
brain scan without automated kilovoltage was 0.92 +/- 0.03 cGy and 0.81 +/- 0.03
cGy for the 1- and 5-year-old phantoms, respectively. Use of the automated
kilovoltage software at 120 kVp, 110 kVp, and 100 kVp resulted in dose reductions
of 9.8%, 17.4%, and 19.6%, respectively, for the 1-year-old phantom and 1.2%,
8.6%, and 17.3%, respectively, for the 5-year-old phantom. The CNR for all
automated kilovoltage scans was within 11% of the control scans for the 1-year
old and within 6% for the 5-year-old phantom. CONCLUSION: Our results show that
automated kilovoltage software is effective for reducing the radiation dose to
the lens of the eye in pediatric patients. Furthermore, the image quality by CNR
remained acceptable within 11% of the baseline for all kilovoltage settings used.
PMID- 29949421
TI - Resumenes al Espanol.
PMID- 29949422
TI - Inference From Facial Expressions Among Adolescents and Young Adults With Down
Syndrome.
AB - The focus of this study was the ability of adolescents and young adults with Down
syndrome to infer meaning from facial expressions in the absence of emotion
labels and use this inference in order to adjust their behavior. Participants
with Down syndrome ( N = 19, mean nonverbal mental age of 5.8 years) and 4- to 7
year-old typically developing children performed a novel task in which happy and
angry faces were provided as feedback for a choice made by the participants. In
making a subsequent choice, the participants with Down syndrome performed
similarly to the 4 year olds, indicating a difficulty using angry faces as
feedback. Individual differences within the group were also apparent.
Implications for the development of social competence are discussed.
PMID- 29949423
TI - Trends in the Educational Placement of Students With Intellectual Disability in
the United States Over the Past 40 Years.
AB - In 1975, federal law mandated that children with disabilities be educated in
their least restrictive environment, or alongside peers without disabilities in
general education classrooms to the maximum extent appropriate. More than 40
years later, I investigated how national trends in educational placement have
changed over time for students with intellectual disability. Specifically, I
examined the degree placements have trended toward less restrictive environments.
I found historical trends of incremental progress toward less restrictive
settings, but no evidence of such progress in recent years. Furthermore, most
students were educated predominantly in segregated settings every year. I discuss
how these findings relate to previous studies, as well as implications for
individualized education program teams and advocates for educational inclusion.
PMID- 29949424
TI - Characteristics and Outcomes of People With Intellectual and Developmental
Disabilities Participating in a Mental Health Court.
AB - This study compares characteristics and outcomes of 70 defendants with and 1,122
without intellectual and developmental disabilities (IDD) participating in a
mental health court. Demographic and clinical characteristics differed, but
criminal justice or program characteristics did not. Age, race, marital status,
living situation, court location, health insurance status, and likelihood of
mental illness or substance abuse diagnosis differed between the two groups. When
controlling for other factors, a diagnosis of IDD did not affect the odds of
negative termination from the court but did reduce the odds of rearrest within 1
year of leaving the court. Some mental health courts exclude people with IDD; the
study concludes inclusion is appropriate.
PMID- 29949426
TI - Resumes en Francais.
PMID- 29949425
TI - Detecting Changes in Support Needs Over Time.
AB - Assessment of support needs has received significant attention in the disability
field, however, little is known about the stability of support needs scores over
time. Data from 82 adults with intellectual and developmental disabilities (IDD)
who were reassessed with the Supports Intensity Scale-Adult (SIS-A) version as
well as the SIS-A Annual Review Protocol (SIS-A ARP) were analyzed. The findings
suggest stability of SIS-A scores over a one- to three-year period in adults with
IDD. Several sections of the SIS-A ARP showed discriminative power, particularly
sections that asked if there had been changes in a subset of specific life
activities assessed on the SIS-A and in medical and behavioral needs.
Implications for further research and practice are discussed.
PMID- 29949428
TI - Predictors Associated With Paid Employment Status of Community and Technical
College Students With Intellectual Disability.
AB - The present study sought to identify predictors associated with paid employment
outcomes for community and technical college students with intellectual
disability (ID). Data used were collected from the Transition and Postsecondary
Programs for Students With Intellectual Disabilities (TPSID) implemented in two
community and technical colleges in the upper Midwest. The participants included
228 students with ID attending college who received supports based on the Check &
Connect model. Results using logistic regression showed that students who only
took inclusive classes, participated in campus events, had prior paid work
experience, and participated in volunteering and/or community service were more
likely to earn at or above minimum wage during their most recent year in the
TPSID program. Implications for policy and practice are discussed.
PMID- 29949427
TI - Using Medicaid Data to Characterize Persons With Intellectual and Developmental
Disabilities in Five U.S. States.
AB - This project sought to identify Medicaid members with intellectual and
developmental disabilities (IDD) in five states (Delaware, Iowa, Massachusetts,
New York, and South Carolina) to develop a cohort for subsequent analyses of
medical conditions and service utilization. We estimated that over 300,000
Medicaid members in these states had IDD. All members with diagnostic codes for
IDD were identified and the three most frequent diagnoses were unspecified
intellectual disability, autism or pervasive developmental disorder, and cerebral
palsy. The percentage of Medicaid members with IDD ranged from 2.3% in New York
to 4.2% in South Carolina. Identifying and characterizing people with IDD is a
first step that could guide public health promotion efforts for this population.
PMID- 29949429
TI - COMPARISON OF CABERGOLINE VERSUS RALOXIFENE ADD-ON THERAPY TO LONG-ACTING
SOMATOSTATIN ANALOGUE IN PATIENTS WITH INADEQUATELY CONTROLLED ACROMEGALY: A
RANDOMIZED OPEN LABEL CLINICAL TRIAL.
AB - OBJECTIVE: The present study aimed to evaluate the efficacy of add-on therapy of
cabergoline versus raloxifene to long-acting somatostatin analogues (SAs) in
patients with inadequately controlled acromegaly. METHODS: This was a
prospective, randomized open label clinical trial. Forty-four patients (22 per
group) completed the study; where participants received either cabergoline (3
mg/week) or raloxifene (60 mg twice daily) add-on therapy for 12 weeks in a
parallel manner. The primary outcome was the rate of reduction in serum insulin
like growth factor 1 (IGF-1) from baseline. Secondary outcomes comprised
normalization of serum IGF-1 for age and sex. RESULTS: Serum IGF-1 was
significantly decreased in both the cabergoline (40.3 +/- 25.6%, P<.001) and
raloxifene (31.5 +/- 24.6%, P<.001) groups, with no significant difference
between arms ( P>.05). Normalization in serum IGF-1 values occurred in 40.9% of
patients who were on cabergoline compared to 45.5% of those receiving raloxifene
( P = .76). The subsequent logistic regression analysis highlighted baseline IGF
1 as a significant predictor of IGF-1 normalization (odds ratio, 0.995; 95%
confidence interval, 0.990-0.999; P = .02). Using the receiver operating
characteristic (ROC) curve analysis for the entire group, the baseline IGF-1
value of 1.47 the upper limit of normal (ULN) was the best cut-off point to
identify patients with normal IGF-1 at the end of the study (sensitivity: 52.6%,
specificity: 84.0%, Yoden's index: 0.366). Full biochemical control of acromegaly
was achieved in 22.7% of patients in the cabergoline group compared to 13.6% of
those in the raloxifene group ( P = .43). CONCLUSION: Cabergoline and raloxifene
add-on therapy could effectively decrease serum IGF-1 level in patients with
inadequately controlled acromegaly. The efficacy profiles of both drugs are
comparable. ABBREVIATIONS: DA = dopamine agonist; FBG = fasting blood glucose; GH
= growth hormone; IGF1 = insulin-like growth factor-1; IQR = interquartile range;
OR = odds ratio; ROC = receiver operating characteristic; SA = somatostatin
analogue; SERM = selective estrogen modulator receptor; ULN = upper limit of
normal.
PMID- 29949431
TI - IMAGING LOCALIZATION AND SURGICAL APPROACH IN THE MANAGEMENT OF ECTOPIC
PARATHYROID ADENOMAS.
AB - OBJECTIVE: ( 1) Review the anatomy and epidemiology of ectopic parathyroid
adenomas (EPAs), ( 2) summarize the role of relevant imaging modalities in the
localization of EPAs, and ( 3) characterize surgical approaches for various
ectopic locations. METHODS: Literature review of published English-language
articles from 1995 through August 2017. RESULTS: Summary of the literature
indicates that the prevalence of EPA is approximately 20% in unexplored patients
with primary hyperparathyroidism, but it is as high as 66% in re-operative
patients. EPAs may be located anywhere from the carotid bifurcation to the aorto
pulmonary window. Ultrasound has limited accuracy in identifying EPAs except near
the thyroid and thyrothymic ligament and requires expert experience from the
user. Among dual-phase 99mTc sestamibi scintigraphy techniques, hybrid imaging
with both single-photon emission computed tomography (SPECT) and computed
tomography (CT) (SPECT/CT) is superior to planar scintigraphy or SPECT alone at
localizing EPAs. Four-dimensional computed tomography (4DCT) precisely delineates
important anatomic relationships and is highly sensitive in localizing EPAs.
Although 4DCT requires radiation, intravenous iodinated contrast, and reader
experience, it is well-equipped to detect lesions at various ectopic sites and
guide the surgical approach. EPAs frequently require alternative surgical
approaches. Re-operative parathyroidectomy may be attempted in patients having
previously undergone bilateral neck exploration by an experienced surgeon once
the lesion is colocalized by 2 repeat imaging modalities. Removal of nonlocalized
disease requires a careful and systematic exploration of superior and inferior
gland locations. CONCLUSION: EPAs pose challenges during both localization and
surgical removal. High-volume experience and multidisciplinary care are necessary
for optimal outcomes. ABBREVIATIONS: CT = computed tomography; 4DCT = 4
dimensional CT; EPA = ectopic parathyroid adenoma; EPG = ectopic parathyroid
gland; PHPT = primary hyperparathyroidism; RLN = recurrent laryngeal nerve; SPECT
= single-photon emission computed tomography; TE = tracheo-esophageal.
PMID- 29949432
TI - THE EFFICACY AND SAFETY OF CO-ADMINISTRATION OF SITAGLIPTIN WITH METFORMIN IN
PATIENTS WITH TYPE 2 DIABETES AT HOSPITAL DISCHARGE.
AB - OBJECTIVE: Few randomized controlled trials have focused on the optimal
management of patients with type 2 diabetes (T2D) during the transition from the
inpatient to outpatient setting. This multicenter open-label study explored a
discharge strategy based on admission hemoglobin A1c (HbA1c) to guide therapy in
general medicine and surgery patients with T2D. METHODS: Patients with HbA1c <=7%
(53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c
between 7 and 9% (53-75 mmol/mol) and those >9% (75 mmol/mol) were discharged on
sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily
dose. The primary outcome was change in HbA1c at 3 and 6 months after discharge.
RESULTS: Mean HbA1c on admission for the entire cohort (N = 253) was 8.70 +/-
2.3% and decreased to 7.30 +/- 1.5% and 7.30 +/- 1.7% at 3 and 6 months (
P<.001). Patients with HbA1c <7% went from 6.3 +/- 0.5% to 6.3 +/- 0.80% and 6.2
+/- 1.0% at 3 and 6 months. Patients with HbA1c between 7 and 9% had a reduction
from 8.0 +/- 0.6% to 7.3 +/- 1.1% and 7.3 +/- 1.3%, and those with HbA1c >9% from
11.3 +/- 1.7% to 8.0 +/- 1.8% and 8.0 +/- 2.0% at 3 and 6 months after discharge
(both P<.001). Clinically significant hypoglycemia (<54 mg/dL) was observed in
4%, 4%, and 7% among patients with a HbA1c <7%, 7 to 9%, and >9%, while a glucose
<40 mg/dL was reported in <1% in all groups. CONCLUSION: The proposed HbA1c-based
hospital discharge algorithm using a combination of sitagliptin-metformin was
safe and significantly improved glycemic control after hospital discharge in
general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood
glucose; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration
rate; HbA1c = hemoglobin A1c; T2D = type 2 diabetes.
PMID- 29949433
TI - TSH-STAINING PITUITARY ADENOMA: A RARE ENTITY WITH CHANGING FACETS.
PMID- 29949434
TI - TSH-STAINING PITUITARY ADENOMAS: RARE, SILENT, AND PLURIHOROMONAL.
AB - OBJECTIVE: To characterize a single referral center experience with thyroid
stimulating hormone (TSH)-staining adenomas. METHODS: A retrospective chart
review was conducted on histopathologic-proven TSH-staining adenomas resected
between 2000-2015 at a single center. Tumors were classified as functional
(hormonally active) or silent (hormonally inactive). Categorical variables were
summarized using counts (n) and percentages; continuous variables were summarized
using medians and ranges. RESULTS: From the 1,065 pituitary adenomas operated, 32
(3.0%) showed diffuse staining for TSH. Median (range) age of patients was 49
years (20 to 77 years), and 21 (66%) were male. Tumor diameter was 20 mm (2 to 37
mm), with 7 (22%) microadenomas and 25 (78%) macroadenomas. Functional tumors (n
= 5, 16%) had median diameter of 10 mm (5 to 21 mm) (2 microadenomas). At
diagnosis, median (range) TSH was 4.3 MUU/mL (1.2 to 6.9 MUU/mL), and free
thyroxine (FT4) was 2.4 ng/dL (2.1 to 3.4 ng/dL). Three tumors stained for TSH
alone, and 2 tumors costained with growth hormone (GH). No cavernous sinus
invasion was seen, and 3 (60%) were considered cured after surgery. Silent tumors
(n = 27, 84%) had median diameter of 20 mm (2 to 37 mm), with 5 (19%)
microadenomas and 22 (81%) macroadenomas. Median (range) TSH was 1.2 MUU/mL (0.48
to 4.6 MUU/mL), and FT4 was 1.2 ng/dL (0.6 to 1.6). Only 2 (7.4%) tumors stained
for TSH alone; the rest were plurihormonal, with GH being the most common.
Cavernous sinus invasion was seen in 7 (27%) of the tumors, and 17 (63%) were
considered surgically cured. CONCLUSION: In our series, 22% of TSH-staining
adenomas were microadenomas, and 84% were silent. Most TSH-staining adenomas were
plurihormonal, particularly costaining with GH. ABBREVIATIONS: alphaSU = alpha
subunit; ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone;
FT3 = free triiodothyronine; FT4 = free thyroxine; GH = growth hormone; LH =
luteinizing hormone; MRI = magnetic resonance imaging; PRL = prolactin; T4 =
thyroxine; TSH = thyroid-stimulating hormone.
PMID- 29949435
TI - Population Genomics of Nymphon australe Hodgson, 1902 (Pycnogonida, Nymphonidae)
in the Western Antarctic.
AB - Within the Southern Ocean, the Antarctic Circumpolar Current is hypothesized to
facilitate a circumpolar distribution for many taxa, even though some, such as
pycnogonids, are assumed to have limited ability to disperse, based on brooding
life histories and adult ambulatory capabilities. With a number of contradictions
to circumpolarity reported in the literature for other pycnogonids, alternative
hypotheses have been explored, particularly for Nymphon australe, the most common
species of Pycnogonida (sea spider) in the Southern Ocean. Glacial events have
been hypothesized to impact the capacity of organisms to colonize suitable areas
without ice coverage as refuge and without the eurybathic capacity to colonize
deeper areas. In this study, we examine populations of one presumed circumpolar
species, the pycnogonid N. australe, from throughout the Western Antarctic, using
a 2b-RAD approach to detect genetic variation with single-nucleotide
polymorphisms. Using this approach, we found that N. australe included two
distinct groups from within >5000-km sampling region. By using a discriminant
analysis of principle components, sparse nonnegative matrix factorization, and
admixture coefficient analysis, two distinctive populations were revealed in the
Western Antarctic: one covered distances greater than 5000 km (Weddell, Western
Antarctic Peninsula, and Ross Sea), and the other shared limited connectivity
entrained within the Amundsen Sea. Under further scrutiny of the 3086 single
nucleotide polymorphisms in the data set, only 78 loci had alignment stacks
between the two populations. We propose that the populations analyzed are
divergent enough to constitute two different species from within this common
Antarctic genus known for its phenotypic plasticity.
PMID- 29949436
TI - Neuronal Development in the Larvae of the Invasive Biofouler Dreissena polymorpha
(Mollusca: Bivalvia), with Special Attention to Sensory Elements and Swimming
Behavior.
AB - Although understanding of the neuronal development of Trochozoa has progressed
recently, little attention has been paid to freshwater bivalves, including
species with a strong ecological impact, such as the zebra mussel (Dreissena
polymorpha). Therefore, an important question might concern how the developing
nervous system is involved in the formation of the rapid and successful invasive
behavior of this species. Our aim was to reveal the neuronal development of
trochophore and veliger larvae of Dreissena, with special attention to the
organization of sensory structures and their possible involvement in detecting
environmental cues. After applying serotonin and FMRFamide immunocytochemistry,
the first serotonin immunoreactive sensory elements appeared 16-18 hours after
fertilization, whereas the first FMRFamide immunoreactive sensory cell was seen
only at 32 hours of development (trochophore stage). Later, sensory elements were
found in three parts of the larval body, including the apical organ, the
posterior region, and the stomach. Although differences in the timing of
appearance and the morphology of cells were observed, the two signaling systems
showed basic similarity in their organization pattern until the end of the
veliger stage. Pharmacological, physiological, and quantitative
immunocytochemical investigations were also performed, suggesting the involvement
of both the serotoninergic system and the FMRFamidergic system in sensomotor
processes. Manipulation of the serotonin synthesis by para-chloroplenylalanine
and 5-hydroxytryptophane, as well as application of increased salinity,
influenced larval swimming activity, both accompanied by changes in
immunofluorescence intensity. We concluded that these two early sensory systems
may play an important role in the development of settlement competency of this
biofouling invasive bivalve, Dreissena.
PMID- 29949438
TI - Getting a Head with Ptychodera flava Larval Regeneration.
AB - Severe injury to the central nervous system of chordates often results in
permanent and irreversible mental and physical challenges. While some chordates
are able to repair and/or regenerate portions of their nervous system, no
chordate has been shown to be able to regenerate all regions of its central
nervous system after catastrophic injury or amputation. Some hemichordates, on
the other hand, are able to efficiently regenerate all neural structures,
including their dorsal, hollow neural tube after complete ablation. Solitary
hemichordates are marine acorn worms and a sister group to the echinoderms. The
hemichordate Ptychodera flava progresses from a pelagic, feeding tornaria larva
to a tripartite benthic worm with an anterior proboscis, a middle collar region,
and a long posterior trunk. The adult worm regenerates all body parts when
bisected in the trunk, but it was unknown whether the regeneration process was
present in tornaria larvae. Now, we show that P. flava larvae are capable of
robust regeneration after bisection through the sagittal, coronal, and axial
planes. We also use antibody staining to show that the apical sensory organ
regenerates a rich, serotonin-positive complex of cells within two weeks after
amputation. Cells labeled with 5-ethynyl-2'-deoxyuridine confirm that
regeneration is occurring through epimorphic processes as new cells are added at
the cut site and throughout the regenerating tissue. This study verifies that P.
flava larvae can be used for future functional studies aimed at identifying the
genetic and morphological mechanisms controlling central nervous system
regeneration in a stem deuterostome.
PMID- 29949437
TI - Sequences of Circadian Clock Proteins in the Nudibranch Molluscs Hermissenda
crassicornis, Melibe leonina, and Tritonia diomedea.
AB - While much is known about the genes and proteins that make up the circadian
clocks in vertebrates and several arthropod species, much less is known about the
clock genes in many other invertebrates, including nudibranchs. The goal of this
project was to identify the RNA and protein products of putative clock genes in
the central nervous system of three nudibranchs, Hermissenda crassicornis, Melibe
leonina, and Tritonia diomedea. Using previously published transcriptomes
(Hermissenda and Tritonia) and a new transcriptome (Melibe), we identified
nudibranch orthologs for the products of five canonical clock genes: brain and
muscle aryl hydrocarbon receptor nuclear translocator like protein 1, circadian
locomotor output cycles kaput, non-photoreceptive cryptochrome, period, and
timeless. Additionally, orthologous sequences for the products of five related
genes-aryl hydrocarbon receptor nuclear translocator like, photoreceptive
cryptochrome, cryptochrome DASH, 6-4 photolyase, and timeout-were determined.
Phylogenetic analyses confirmed that the nudibranch proteins were most closely
related to known orthologs in related invertebrates, such as oysters and
annelids. In general, the nudibranch clock proteins shared greater sequence
similarity with Mus musculus orthologs than Drosophila melanogaster orthologs,
which is consistent with the closer phylogenetic relationships recovered between
lophotrochozoan and vertebrate orthologs. The suite of clock-related genes in
nudibranchs includes both photoreceptive and non-photoreceptive cryptochromes, as
well as timeout and possibly timeless. Therefore, the nudibranch clock may
resemble the one exhibited in mammals, or possibly even in non-drosopholid
insects and oysters. The latter would be evidence supporting this as the
ancestral clock for bilaterians.
PMID- 29949440
TI - Index for Volume 234.
PMID- 29949439
TI - Losing Reproduction: Effect of High Temperature on Female Biochemical Composition
and Egg Quality in a Freshwater Crustacean with Direct Development, the Red
Cherry Shrimp, Neocaridina davidi (Decapoda, Atyidae).
AB - Maternal provisioning is particularly important in invertebrates with abbreviated
development because large energy reserves must be provided for the developing
embryo. In this context, the objective of the present study was to analyze in an
aquatic invertebrate with direct development the effect of temperature on female
biochemical composition and reserve allocation to maturing ovaries, which
determine egg quality. A decapod crustacean, the freshwater shrimp Neocaridina
davidi, was used as experimental model. Newly hatched juveniles were exposed to
28 degrees C or 33 degrees C. Females showed mature ovaries and spawned at 28
degrees C (control ovigerous females), but no ovigerous female was found at 33
degrees C. After a 200-day period, half of the females at 33 degrees C were
transferred to 28 degrees C, where they rapidly showed mature ovaries and
spawned (transferred ovigerous females). Ovigerous females and females that did
not spawn at 28 degrees C (control non-ovigerous females) and at 33 degrees C
(high-temperature non-ovigerous females) were sacrificed to determine their
biochemical composition. The number, volume, weight, and biochemical composition
of the eggs from transferred and control ovigerous females were also analyzed as
indicators of their quality. Female biochemical composition was not influenced by
temperature, because control and high-temperature non-ovigerous females had
similar lipid, protein, and glycogen contents. However, ovarian maturation and
spawning were inhibited at 33 degrees C, which indicates a negative effect of
this temperature on nutrient transfer to the oocytes. This effect was rapidly
reversed after females were moved to 28 degrees C; the eggs from control and
transferred ovigerous females were of similar quality, except for a lower protein
content in the latter. The present results provide valuable information on
reserve allocation to reproduction under thermal stress.
PMID- 29949441
TI - Embryonic Development in the Peppermint Shrimp, Lysmata boggessi (Caridea:
Lysmatidae).
AB - There are a limited number of model species for decapod experimental embryology.
To improve our understanding of developmental pattern evolution in the Decapoda,
here we describe the early embryonic development of the caridean shrimp Lysmata
boggessi, from immediately after fertilization to the hatching of the zoea larva,
using fluorescence microscopy and whole-mount nuclear staining with 4',6
diamidino-2-phenylindole. Lysmata boggessi follows the standard caridean pattern
of early development, with early holoblastic cleavage that will later become
superficial, to form a blastoderm. We found no evidence of stereotypical cleavage
and the formation of blastomere interlocking bands, which suggests there is
diversity in developmental patterns within the Caridea. Gastrulation starts 37
hours after fertilization, and the embryonized nauplius is formed 2 days later.
Enlarged headlobes, early retinal differentiation, and delayed pereopod
development are characteristics of the post-naupliar stages in this species. To
facilitate comparative studies with other crustacean species, we propose a
staging method based on our findings. Lysmata boggessi is a protandric
simultaneous hermaphrodite that is relatively easy to breed in captivity and
amenable to laboratory experimentation in studies of embryonic development.
PMID- 29949443
TI - Associations Between the DSM-5 Section III Trait Model and Impairments in
Functioning in Singaporean College Students.
AB - The Alternative Model for Personality Disorders (AMPD) in Section III of the
Diagnostic and Statistical Manual of Mental Disorders, fifth edition, recommends
the joint consideration of personality disorder severity (i.e., dysfunction) and
style (i.e., trait profile) in personality disorder diagnosis. The current study
examined the association between maladaptive personality dysfunction and traits
using a Singaporean student sample (N = 360). A subsample (n = 151) had informant
ratings of personality traits on target participants. Results indicated that
dysfunctions and traits were substantially correlated, calling into question
their distinctiveness. However, the overlap was less pronounced when informant
ratings were used. Consistent with prior research, the validity of the PID-5
trait model appeared to be supported, as observed in the meaningful differential
relations with different impairment outcomes. These findings represent a
preliminary yet critical test of the generalizability of the AMPD to a non
Western cultural group.
PMID- 29949442
TI - Complete Local and Abscopal Responses from a Combination of Radiation and
Nivolumab in Refractory Hodgkin's Lymphoma.
AB - Until recently, patients with relapsed Hodgkin's lymphoma after brentuximab
vedotin (Bv) treatments had poor treatment outcomes. Checkpoint inhibitors such
as nivolumab and pembrolizumab that bind to and inhibit programmed cell death
protein-1 (PD-1), have demonstrated an overall response rate of 70% in Hodgkin's
lymphoma patients; however, complete response is still low at 20% with median
progression-free survival of 14 months. There are ongoing clinical studies to
seek out synergistic combinations, with the goal of improving the complete
response rates for the cure of Hodgkin's lymphoma. Although radiotherapy has a
limited survival benefit in such refractory patients, several preclinical models
and anecdotal clinical evidence have suggested that combining local tumor
irradiation with checkpoint inhibitors can produce systemic regression of distant
tumors, an abscopal effect. Most of these reported studies on the response with
local conformal radiotherapy and checkpoint inhibitors in combination with the
anti-cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) antibody-ipilimumab are
in melanoma. Here we report in our case series that the checkpoint inhibitors
that block CTLA4 and B7-homolog 1 (B7-H1) or PD-1 in preclinical radiotherapy
models have shown an increased the rate of tumor regression. Our case series
demonstrates that combining local irradiation with anti-PD-1 checkpoint blockade
treatment is feasible and synergistic in refractory Hodgkin's lymphoma.
Correlative studies also suggest that the expression of programmed death-ligand 1
(PD-L1), DNA damage response and mutational tumor burden can be used as potential
biomarkers for treatment response.
PMID- 29949444
TI - Construct Validity of the McLean Screening Instrument for Borderline Personality
Disorder in Two Singaporean Samples.
AB - This study examined the construct validity of the McLean Screening Instrument for
Borderline Personality Disorder (MSI-BPD) in a consecutive sample of adult
psychiatric patients (n = 128) and a separate sample of undergraduate students (n
= 289) in Singapore. Participants were administered the MSI-BPD and other
measures assessing related symptoms of BPD. Patients were also administered a
semistructured interview by interviewers blind to their MSI-BPD scores.
Confirmatory factor analyses revealed a unique three-factor solution, consisting
of affect dysregulation, self-disturbances, and behavioral and interpersonal
dysregulation. In both samples, the MSI-BPD demonstrated good internal
consistency and convergent validity. The measure also showed good discriminant
validity and predictive accuracy (AUC = .82), with an optimal cut-off score of
7.5. Overall, the findings suggest that BPD is a valid and coherent clinical
construct in Singapore, and point to the need to further clarify the presentation
and etiology of BPD in this cultural context.
PMID- 29949445
TI - Undervaluing Gratitude: Expressers Misunderstand the Consequences of Showing
Appreciation.
AB - Expressing gratitude improves well-being for both expressers and recipients, but
we suggest that an egocentric bias may lead expressers to systematically
undervalue its positive impact on recipients in a way that could keep people from
expressing gratitude more often in everyday life. Participants in three
experiments wrote gratitude letters and then predicted how surprised, happy, and
awkward recipients would feel. Recipients then reported how receiving an
expression of gratitude actually made them feel. Expressers significantly
underestimated how surprised recipients would be about why expressers were
grateful, overestimated how awkward recipients would feel, and underestimated how
positive recipients would feel. Expected awkwardness and mood were both
correlated with participants' willingness to express gratitude. Wise decisions
are guided by an accurate assessment of the expected value of action.
Underestimating the value of prosocial actions, such as expressing gratitude, may
keep people from engaging in behavior that would maximize their own-and others'
well-being.
PMID- 29949446
TI - Firearm Injuries and Violence Prevention - The Potential Power of a Surgeon
General's Report.
PMID- 29949447
TI - Lipid trafficking by yeast Snx4 family SNX-BAR proteins promotes autophagy and
vacuole membrane fusion.
AB - Cargo-selective and nonselective autophagy pathways employ a common core
autophagy machinery that directs biogenesis of an autophagosome that eventually
fuses with the lysosome to mediate turnover of macromolecules. In yeast (
Saccharomyces cerevisiae) cells, several selective autophagy pathways fail in
cells lacking the dimeric Snx4/Atg24 and Atg20/Snx42 sorting nexins containing a
BAR domain (SNX-BARs), which function as coat proteins of endosome-derived
retrograde transport carriers. It is unclear whether endosomal sorting by Snx4
proteins contributes to autophagy. Cells lacking Snx4 display a deficiency in
starvation induced, nonselective autophagy that is severely exacerbated by
ablation of mitochondrial phosphatidylethanolamine synthesis. Under these
conditions, phosphatidylserine accumulates in the membranes of the endosome and
vacuole, autophagy intermediates accumulate within the cytoplasm, and homotypic
vacuole fusion is impaired. The Snx4-Atg20 dimer displays preference for binding
and remodeling of phosphatidylserine-containing membrane in vitro, suggesting
that Snx4-Atg20-coated carriers export phosphatidylserine-rich membrane from the
endosome. Autophagy and vacuole fusion are restored by increasing
phosphatidylethanolamine biosynthesis via alternative pathways, indicating that
retrograde sorting by the Snx4 family sorting nexins maintains
glycerophospholipid homeostasis required for autophagy and fusion competence of
the vacuole membrane.
PMID- 29949448
TI - Ambulance-attended opioid overdoses: An examination into overdose locations and
the role of a safe injection facility.
AB - BACKGROUND: Although the United States and numerous other countries are amidst an
opioid overdose crisis, access to safe injection facilities remains limited.
METHODS: We used prospective data from ambulance journals in Oslo, Norway, to
describe the patterns, severity, and outcomes of opioid overdoses and compared
these characteristics among various overdose locations. We also examined what
role a safe injection facility may have had on these overdoses. RESULTS: Based on
48,825 ambulance calls, 1054 were for opioid overdoses from 465 individuals
during 2014 and 2015. The rate of calls for overdoses was 1 out of 48 of the
total ambulance calls. Males made up the majority of the sample (n = 368, 79%),
and the median age was 35 (range: 18-96). Overdoses occurred in public locations
(n = 530, 50.3%), the safe injection facility (n = 353, 33.5%), in private homes
(n = 83, 7.9%), and other locations (n = 88, 8.3%). Patients from the safe
injection facility and private homes had similarly severe initial clinical
symptoms (Glasgow Coma Scale median =3 and respiratory frequency median =4
breaths per minute) when compared with other locations, yet the majority from the
safe injection facility did not require further ambulance transport to the
hospital (n = 302, 85.6%). Those overdosed in public locations (odds ratio [OR] =
1.66, 95% confidence interval [CI] = 1.17-2.35), and when the safe injection
facility was closed (OR =1.4, 95% CI =1.04-1.89), were more likely to receive
transport for further treatment. CONCLUSIONS: Our findings suggest that the
opening hours at the safe injection facility and the overdose location may impact
the likelihood of ambulance transport for further treatment.
PMID- 29949449
TI - Motivational interviewing training of substance use treatment professionals: A
systematic review.
AB - BACKGROUND: Through evaluations of training programs, systematic reviews, and
meta-analyses, advances in identifying best practices for disseminating
motivational interviewing (MI) have emerged. To advance this work further,
inclusion of thorough descriptions of the following is needed in research
publications: study (design, trainee characteristics, setting characteristics),
training and coaching methods (if applicable), trainer qualifications, and
evaluation of MI skills. METHODS: The purpose of this study was to systematically
evaluate the research on MI training of substance use treatment professionals for
the inclusion of such descriptions. Twenty-five studies were reviewed using a
scoring rubric developed by the authors. RESULTS: Just over two thirds of the
studies (68%) were randomized controlled trials of MI training. The majority of
studies provided information about (a) trainee characteristics (professional
background = 76%, education = 60%, experience = 56%); (b) setting characteristics
(80%); (c) training methods (format = 96%, length = 92%); (d) coaching (76%); and
(e) evaluation of MI skills (92%). CONCLUSION: Findings suggest advancements in
MI training studies since previous reviews, especially in regards to the
inclusion of feedback and coaching. However, this review also found that
inconsistencies in methods and reporting of training characteristics, as well as
limited follow-up assessment of trainees' skill, continue to limit knowledge of
effective training methods.
PMID- 29949450
TI - Hepatitis C cascade of care among people who inject drugs in Vancouver, Canada.
AB - BACKGROUND: People who inject drugs (PWID) have high rates of hepatitis C virus
(HCV) infection. Little is known about the rates of diagnosis and treatment for
HCV among PWID. Therefore, this study aims to characterize the cascade of care in
Vancouver, Canada, to improve HCV treatment access and delivery for PWID.
METHODS: Data were derived from 3 prospective cohort studies of PWID in
Vancouver, Canada, between December 2005 and May 2015. The progression of
participants was identified through 5 steps in the cascade of care: (1) chronic
HCV; (2) linkage to HCV care; (3) liver disease assessment; (4) initiation of
treatment; and (5) completion of treatment. Predictors of undergoing liver
disease assessment for HCV treatment were identified using a multivariable
extended Cox regression model. RESULTS: Among 1571 participants with chronic HCV,
1359 (86.5%) had ever been linked to care, 1257 (80.0%) had undergone liver
disease assessment, 163 (10.4%) had ever started HCV treatment, and 71 (4.5%) had
ever completed treatment. In multivariable analyses, human immunodeficiency virus
(HIV) seropositivity, use of methadone maintenance therapy, and hospitalization
in the past 6 months were independently and positively associated with undergoing
liver disease assessment (all P < .001), whereas daily heroin injection was
independently and negatively associated with undergoing liver disease assessment
(P < .001). CONCLUSIONS: Among this cohort of PWID, few had been started on or
completed treatment for HCV. These findings highlight the need to improve the
prescribing of HCV treatment among PWID with active substance use.
PMID- 29949451
TI - Accreditation of Clinical Research Sites - Moving Forward.
PMID- 29949453
TI - Integrating injectable opioid agonist treatment into a drug treatment court
program: A case study.
AB - BACKGROUND: A substantial proportion of individuals involved with the North
American criminal justice system are convicted for drug-related activities. Drug
treatment court (DTC) programs were developed as an alternative to incarceration
for drug-related offences and aim to prioritize addiction treatment and improve
health and social outcomes; however, only a fraction of DTC participants have
access to first-line medications for opioid use disorder (OUD). Further, despite
emerging evidence for the efficacy of injectable opioid agonist therapy (OAT) in
treating individuals with severe OUD where past treatment attempts with first
line therapies have been unsuccessful, this treatment has never, to our
knowledge, been implemented in correctional settings. CASE: An individual in
their 50s with a history of severe OUD, multiple interactions with the criminal
justice system, and prior unsuccessful treatment attempts with methadone was
initiated on injectable treatment with diacetylmorphine. The patient received 300
mg of diacetylmorphine witnessed 3 times daily at a supervised injection clinic.
During a 1.5-year stabilization phase, the patient's illicit opioid use
significantly reduced. They subsequently enrolled in a DTC program for drug
related charges preceding initiation on injectable OAT and remained on this
therapy during 16 months in DTC. Following graduation from DTC, the patient
continued to receive treatment and returned to gainful employment in the
community, with no further charges or episodes of incarceration. DISCUSSION: This
case describes the successful completion of a DTC program by an individual
prescribed injectable OAT for severe OUD. The patient's treatment plan played an
integral role in DTC graduation and long-term adherence, leading to improved
health and social outcomes, including cessation of illicit drug use, enhanced
quality of life, and improved social functioning. The case highlights the
potential benefits of a stepped and integrated approach to addiction treatment in
DTC programs.
PMID- 29949452
TI - Rab18 is not necessary for lipid droplet biogenesis or turnover in human mammary
carcinoma cells.
AB - Rab GTPases recruit peripheral membrane proteins and can define organelle
identity. Rab18 localizes to the endoplasmic reticulum (ER) but also to lipid
droplets (LDs), where it has been implicated in effector protein recruitment and
in defining LD identity. Here, we studied Rab18 localization and function in a
human mammary carcinoma cell line. Rab18 localized to the ER and to LD membranes
on LD induction, with the latter depending on the Rab18 activation state. In
cells lacking Rab18, LDs were modestly reduced in size and numbers, but we found
little evidence for Rab18 function in LD formation, LD turnover on cell
starvation, or the targeting of several proteins to LDs. We conclude that Rab18
is not a general, necessary component of the protein machinery involved in LD
biogenesis or turnover.
PMID- 29949454
TI - Barriers to accessing treatment for pregnant women with opioid use disorder in
Appalachian states.
AB - BACKGROUND AND AIMS: Opioid agonist therapies (OATs) are highly effective
treatments for opioid use disorders (OUDs), especially for pregnant women; thus,
improving access to OAT is an urgent public policy goal. Our objective was to
determine if insurance and pregnancy status were barriers to obtaining access to
OAT in 4 Appalachian states disproportionately impacted by the opioid epidemic.
METHODS: Between April and May 2017, we conducted phone surveys of OAT providers,
opioid treatment programs (OTPs), and outpatient buprenorphine providers, in
Kentucky, North Carolina, Tennessee, and West Virginia. Survey response rates
were 59%. Logistic models for dichotomous outcomes (e.g., patient acceptance) and
negative binomial models were created for count variables (e.g., wait time),
overall and for pregnant women. RESULTS: The majority of OAT providers were
accepting new patients; however, providers were less likely to treat pregnant
women (91% vs. 75%; p < .01). OTPs were more likely to accept new patients than
waivered buprenorphine providers (97% vs. 83%; p = .01); rates of accepting
pregnant patients were lower in both (91% and 53%; p < .01). OTPs and
buprenorphine providers accepted cash payments for services at high rates (OTP:
100%; buprenorphine: 89.4%; p < .01); Medicaid and private insurance were
accepted at lower rates. In adjusted models, providers were less likely to accept
pregnant women if they took any insurance (adjusted odds ratio [aOR] = 0.15, 95%
confidence interval [CI]: 0.03-0.68) or were a buprenorphine provider (aOR =
0.09, 95% CI: 0.02-0.37). CONCLUSIONS: We found that OAT providers frequently did
not accept any insurance and frequently did not treat pregnant women in an area
of the country disproportionately affected by the opioid epidemic. Policymakers
could prioritize improvements in provider training (e.g., training of
obstetricians to become buprenorphine prescribers) as a means to enhance access
to pregnant women or enhancing reimbursement rates as a means of improving
insurance acceptance for OAT.
PMID- 29949455
TI - Immediate effects of interoceptive awareness training through Mindful Awareness
in Body-oriented Therapy (MABT) for women in substance use disorder treatment.
AB - BACKGROUND: Sensory information gained through interoceptive awareness may play
an important role in affective behavior and successful inhibition of drug use.
This study examined the immediate pre-post effects of the mind-body intervention
Mindful Awareness in Body-oriented Therapy (MABT) as an adjunct to women's
substance use disorder (SUD) treatment. MABT teaches interoceptive awareness
skills to promote self-care and emotion regulation. METHODS: Women in intensive
outpatient treatment (IOP) for chemical dependency (N = 217) at 3 community
clinics in the Pacific Northwest of the United States were recruited and randomly
assigned to one of 3 study conditions: MABT + treatment as usual (TAU), women's
health education (WHE) +TAU (active control condition), and TAU only. At baseline
and 3 months post-intervention, assessments were made of interoceptive awareness
skills and mindfulness, emotion regulation (self-report and psychophysiological
measures), symptomatic distress (depression and trauma-related symptoms), and
substance use (days abstinent) and craving. Changes in outcomes across time were
assessed using multilevel mixed-effects linear regression. RESULTS: Findings
based on an intent-to-treat approach demonstrated significant improvements in
interoceptive awareness and mindfulness skills, emotion dysregulation (self
report and psychophysiology), and days abstinent for women who received MABT
compared with the other study groups. Additional analyses based on participants
who completed the major components of MABT (at least 75% of the intervention
sessions) revealed these same improvements as well as reductions in depressive
symptoms and substance craving. CONCLUSIONS: Findings that interoceptive training
is associated with health outcomes for women in SUD treatment are consistent with
emerging neurocognitive models that link interoception to emotion regulation and
to related health outcomes, providing knowledge critical to supporting and
improving SUD treatment.
PMID- 29949456
TI - Neural signatures of chronic accessibility in parent - adult child attachment
bonds.
AB - Some of the closest reciprocal relationships are between parents and their
children. As part of the attachment characterizing many parent-child bonds,
individuals form mental representations that are chronically accessible and
calibrate expectations for future relationships. We predict that there exist
unique neural signatures of this chronic accessibility. Young (N = 29, 16
females) and older adults (N = 27, 12 females) made trait judgments for parent or
child, respectively, during fMRI scanning. Multivariate analysis identified whole
brain patterns of activation that covaried with the magnitude of parent-child
attachment when thinking about that individual. Higher levels of parent and child
attachment were associated with lower neural recruitment in anterior cingulate
cortex, amygdala, posterior cingulate cortex, medial temporal lobe, and occipital
face area. Results provide novel evidence for neural signatures of chronic
accessibility, as bringing to mind one's attached parent or child requires less
engagement of brain regions involved in distress relief, memory, and facial
processing.
PMID- 29949457
TI - Positive Health Benefits of Peer Support and Connections for College Students
With Type 1 Diabetes Mellitus.
AB - Purpose The purpose of this study is to examine the characteristics and health
outcomes of college students with type 1 diabetes mellitus (T1DM) as it relates
to membership in a local university-based diabetes student organization. Methods
This descriptive, correlational research design is a secondary analysis of data.
The sample consisted of nationally representative young adults in college (n =
317) between 18 and 30 years of age who were diagnosed with T1DM. Data were
collected during April 2017 using a secure electronic diabetes management survey
to inquire about self-reported barriers to diabetes management, hypoglycemia, and
diabetic ketoacidosis of members of a diabetes organization. Results Students
were evenly distributed from freshman to senior year of college with a slight
decrease at the graduate level. Students who were affiliated members of a student
led diabetes student organization were less likely to report increased levels of
isolation, depressive symptoms, and anxiety related to their diabetes than were
general members. Conclusion Participation in a university-based diabetes student
organization on campus and connecting with other college students with diabetes
may have health benefits. In conclusion, the current study underscores the
potential importance of peer-led, diabetes-specific support for adolescents
emerging into adulthood.
PMID- 29949459
TI - A Computationally Efficient Visual Saliency Algorithm Suitable for an Analog CMOS
Implementation.
AB - Computer vision algorithms are often limited in their application by the large
amount of data that must be processed. Mammalian vision systems mitigate this
high bandwidth requirement by prioritizing certain regions of the visual field
with neural circuits that select the most salient regions. This work introduces a
novel and computationally efficient visual saliency algorithm for performing this
neuromorphic attention-based data reduction. The proposed algorithm has the added
advantage that it is compatible with an analog CMOS design while still achieving
comparable performance to existing state-of-the-art saliency algorithms. This
compatibility allows for direct integration with the analog-to-digital conversion
circuitry present in CMOS image sensors. This integration leads to power savings
in the converter by quantizing only the salient pixels. Further system-level
power savings are gained by reducing the amount of data that must be transmitted
and processed in the digital domain. The analog CMOS compatible formulation
relies on a pulse width (i.e., time mode) encoding of the pixel data that is
compatible with pulse-mode imagers and slope based converters often used in
imager designs. This letter begins by discussing this time-mode encoding for
implementing neuromorphic architectures. Next, the proposed algorithm is derived.
Hardware-oriented optimizations and modifications to this algorithm are proposed
and discussed. Next, a metric for quantifying saliency accuracy is proposed, and
simulation results of this metric are presented. Finally, an analog synthesis
approach for a time-mode architecture is outlined, and postsynthesis transistor
level simulations that demonstrate functionality of an implementation in a modern
CMOS process are discussed.
PMID- 29949458
TI - Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21
family member calcyon.
AB - Transport of late endosomes and lysosome-related organelles (LE/LROs) in axons is
essential for supplying synaptic cargoes and for removing damaged macromolecules.
Defects in this system are implicated in a range of human neurodegenerative and
neurodevelopmental disorders. The findings reported here identify a novel
mechanism regulating LE/LRO transport based on the coordinated coupling of
microtubule motors and vesicle coat proteins to the neuron-enriched,
transmembrane protein calcyon (Caly). We found that the cytoplasmic C-terminus of
Caly pulled down proteins involved in microtubule-dependent transport (DIC,
KIF5A, p150Glued, Lis1) and organelle biogenesis (AP-1 and AP-3) from the brain.
In addition, RNA interference-mediated knockdown of Caly increased the percentage
of static LE/LROs labeled by LysoTracker in cultured dorsal root ganglion axons.
In contrast, overexpression of Caly stimulated movement of organelles positive
for LysoTracker or the AP-3 cargo GFP-PI4KIIalpha. However, a Caly mutant (ATEA)
that does not bind AP-3 was unable to pull down motor proteins from brain, and
expression of the ATEA mutant failed to increase either LE/LRO flux or levels of
associated dynein. Taken together, these data support the hypothesis that Caly is
a multifunctional scaffolding protein that regulates axonal transport of LE/LROs
by coordinately interacting with motor and vesicle coat proteins.
PMID- 29949460
TI - ASIC Implementation of a Nonlinear Dynamical Model for Hippocampal Prosthesis.
AB - A hippocampal prosthesis is a very large scale integration (VLSI) biochip that
needs to be implanted in the biological brain to solve a cognitive dysfunction.
In this letter, we propose a novel low-complexity, small-area, and low-power
programmable hippocampal neural network application-specific integrated circuit
(ASIC) for a hippocampal prosthesis. It is based on the nonlinear dynamical model
of the hippocampus: namely multi-input, multi-output (MIMO)-generalized Laguerre
Volterra model (GLVM). It can realize the real-time prediction of hippocampal
neural activity. New hardware architecture, a storage space configuration scheme,
low-power convolution, and gaussian random number generator modules are proposed.
The ASIC is fabricated in 40 nm technology with a core area of 0.122 mm[Formula:
see text] and test power of 84.4 [Formula: see text]W. Compared with the design
based on the traditional architecture, experimental results show that the core
area of the chip is reduced by 84.94% and the core power is reduced by 24.30%.
PMID- 29949461
TI - Active Inference, Belief Propagation, and the Bethe Approximation.
AB - When modeling goal-directed behavior in the presence of various sources of
uncertainty, planning can be described as an inference process. A solution to the
problem of planning as inference was previously proposed in the active inference
framework in the form of an approximate inference scheme based on variational
free energy. However, this approximate scheme was based on the mean-field
approximation, which assumes statistical independence of hidden variables and is
known to show overconfidence and may converge to local minima of the free energy.
To better capture the spatiotemporal properties of an environment, we
reformulated the approximate inference process using the so-called Bethe
approximation. Importantly, the Bethe approximation allows for representation of
pairwise statistical dependencies. Under these assumptions, the minimizer of the
variational free energy corresponds to the belief propagation algorithm, commonly
used in machine learning. To illustrate the differences between the mean-field
approximation and the Bethe approximation, we have simulated agent behavior in a
simple goal-reaching task with different types of uncertainties. Overall, the
Bethe agent achieves higher success rates in reaching goal states. We relate the
better performance of the Bethe agent to more accurate predictions about the
consequences of its own actions. Consequently, active inference based on the
Bethe approximation extends the application range of active inference to more
complex behavioral tasks.
PMID- 29949462
TI - A New Foreperiod Effect on Intertrial Phase Coherence. Part I: Existence and
Behavioral Relevance.
AB - This letter makes scientific and methodological contributions. Scientifically, it
demonstrates a new and behaviorally relevant effect of temporal expectation on
the phase coherence of the electroencephalogram (EEG). Methodologically, it
introduces novel methods to characterize EEG recordings at the single-trial
level. Expecting events in time can lead to more efficient behavior. A remarkable
finding in the study of temporal expectation is the foreperiod effect on reaction
time, that is, the influence on reaction time of the delay between a warning
signal and a succeeding imperative stimulus to which subjects are instructed to
respond as quickly as possible. Here we study a new foreperiod effect in an
audiovisual attention-shifting oddball task in which attention-shift cues
directed the attention of subjects to impendent deviant stimuli of a given
modality and therefore acted as warning signals for these deviants. Standard
stimuli, to which subjects did not respond, were interspersed between warning
signals and deviants. We hypothesized that foreperiod durations modulated
intertrial phase coherence (ITPC, the degree of phase alignment across multiple
trials) evoked by behaviorally irrelevant standards and that these modulations
are behaviorally meaningful. Using averaged data, we first observed that ITPC
evoked by standards closer to the warning signal was significantly different from
that evoked by standards further away from it, establishing a new foreperiod
effect on ITPC evoked by standards. We call this effect the standard foreperiod
(SFP) effect on ITPC. We reasoned that if the SFP influences ITPC evoked by
standards, it should be possible to decode the former from the latter on a trial
by-trial basis. We were able to do so showing that this effect can be observed in
single trials. We demonstrated the behavioral relevance of the SFP effect on ITPC
by showing significant correlations between its strength and subjects' behavioral
performance.
PMID- 29949463
TI - Optimal Decoding of Dynamic Stimuli by Heterogeneous Populations of Spiking
Neurons: A Closed-Form Approximation.
AB - Neural decoding may be formulated as dynamic state estimation (filtering) based
on point-process observations, a generally intractable problem. Numerical
sampling techniques are often practically useful for the decoding of real neural
data. However, they are less useful as theoretical tools for modeling and
understanding sensory neural systems, since they lead to limited conceptual
insight into optimal encoding and decoding strategies. We consider sensory neural
populations characterized by a distribution over neuron parameters. We develop an
analytically tractable Bayesian approximation to optimal filtering based on the
observation of spiking activity that greatly facilitates the analysis of optimal
encoding in situations deviating from common assumptions of uniform coding.
Continuous distributions are used to approximate large populations with few
parameters, resulting in a filter whose complexity does not grow with population
size and allowing optimization of population parameters rather than individual
tuning functions. Numerical comparison with particle filtering demonstrates the
quality of the approximation. The analytic framework leads to insights that are
difficult to obtain from numerical algorithms and is consistent with biological
observations about the distribution of sensory cells' preferred stimuli.
PMID- 29949464
TI - Silver sulfadiazine nanoethogel for burn healing: characterization and
investigation of its in vivo effects.
AB - AIM: Nanoethosomal formulation containing silver sulfadiazine (SSD) was used to
reduce bacterial burden and healing time in burn injuries. MATERIALS & METHODS:
Ethosomal formulations were characterized for their size, zeta-potential,
morphology, drug encapsulation efficiency and in vitro release kinetics of SSD.
RESULTS: The optimized nanoethosomal suspension with a size of 206.7 +/- 1.18,
and zeta-potential value of -67.3 +/- 0.45 mV exhibited a high SSD encapsulation
efficiency (92.03 +/- 0.79%). Results of antimicrobial tests indicated SSD-loaded
ethosome formulation led to a significant reduction of colony number.
Histopathological results demonstrated a wound contraction rate of 96.83% for the
group treated with SSD ethosomal gel while untreated group showed 59.41%.
CONCLUSION: The SSD ethogels promotes the therapeutic effect of SSD for burn
treatment.
PMID- 29949465
TI - Intestinal uptake and transport of albumin nanoparticles: potential for oral
delivery.
AB - AIM: To explore the potential of albumin nanoparticles for oral drug delivery.
METHODS: Sub-150 nm human serum albumin nanoparticles were fabricated via a
desolvation technique. Nanoparticle cell uptake and epithelial translocation were
tested in Caco-2 monolayers, while comparing with albumin solution. RESULTS: Data
suggest epithelial transcytosis of albumin, applied in solution form, via
neonatal Fc receptor. Cell uptake of albumin nanoparticles demonstrated behaviors
indicating a different cell uptake pathway compared with albumin solution.
Importantly, application of equivalent concentrations of albumin solution or
nanoparticles resulted in higher epithelial transport capacity of the latter,
suggesting improvement of intestinal delivery via nanoformulation. CONCLUSION:
This study highlights for the first time that simply fabricated, nontoxic human
serum albumin nanoparticles may find application in oral drug delivery.
PMID- 29949466
TI - Nanostructured lipid carriers-based thermosensitive eye drops for enhanced,
sustained delivery of dexamethasone.
AB - AIM: Nanostructured lipid carriers in-gel (NLCs-gel) were prepared to enhance and
improve the ocular delivery of dexamethasone. Materials & methods: NLCs
containing dexamethasone prepared by high-pressure homogenization were
characterized and dispersed into thermosensitive gels (Pluronic F127 and F68 as
gels material). In vitro drug release studies, ocular irritation tests, ex vivo
corneal penetration and drug dynamics of NLCs and NLCs-gel were evaluated in
aqueous humor. RESULTS: NLCs-gel exhibited a rapid sol-gel transition at 34.4
degrees C and presented nano-sized, narrowly distributed particles. Corneal
penetration studies revealed steady sustained drug release (Ritger-Peppas); NLCs
gel increased ocular bioavailability by prolonging precorneal retention time and
improving corneal permeation. CONCLUSION: These findings suggest developing NLCs
gel for potential treatment of posterior segment eye diseases.
PMID- 29949468
TI - Unified D-alpha-Tocopherol 5-Fu/SAHA bioconjugates self-assemble as complex
nanodrug for optimized combination therapy.
AB - AIM: To optimize the synergistic efficacy of combination therapy with controlled
molar ratio, complex small molecule-based nanodrug (Co-SMND) of 5-fluorouracil (5
Fu)/vorinostat (SAHA) was developed. MATERIALS & METHODS: Co-SMND with various
ratios of 5-Fu-D-alpha-tocopherol (VE)/SAHA-VE were prepared and characterized
including co-assembly mechanism, hydrolytic stability, cytotoxicity, synergistic
effect and apoptosis inducing ability. The antitumor activity, systematic
toxicity and biodistribution of optimized Co-SMND were evaluated in CT-26 bearing
BALB/c mouse. RESULTS: Maximal synergistic effect of Co-SMND could be obtained
via simply adjusting the feeding molar ratio. The optimized Co-SMND showed
superior in vivo antitumor efficacy, upregulated security and selective
intratumoral accumulation. CONCLUSION: Such Co-SMND is of great significance for
future clinical translation, and would be an efficient platform for combination
chemotherapy.
PMID- 29949467
TI - Noninvasive imaging of nanoparticle-labeled transplant populations within polymer
matrices for neural cell therapy.
AB - AIM: To develop a 3D neural cell construct for encapsulated delivery of
transplant cells; develop hydrogels seeded with magnetic nanoparticle (MNP)
labeled cells suitable for cell tracking by MRI. MATERIALS & METHODS: Astrocytes
were exogenously labeled with MRI-compatible iron-oxide MNPs prior to intra
construct incorporation within a 3D collagen hydrogel. RESULTS: A connective,
complex cellular network was clearly observable within the 3D constructs, with
high cellular viability. MNP accumulation in astrocytes provided a hypointense
MRI signal at 24 h & 14 days. CONCLUSION: Our findings support the concept of
developing a 3D construct possessing the dual advantages of (i) support of long
term cell survival of neural populations with (ii) the potential for noninvasive
MRI-tracking of intra-construct cells for neuroregenerative applications.
PMID- 29949469
TI - Zinc-doped copper oxide nanocomposites reverse temozolomide resistance in
glioblastoma by inhibiting AKT and ERK1/2.
AB - AIM: To assess the effect of zinc-doped copper oxide nanocomposites (nZn-CuO NPs)
on glioblastoma therapy. MATERIALS & METHODS: nZn-CuO NPs were synthesized by
sonochemical method and its antitumor effects and underlying molecular mechanisms
were investigated both in vitro and in vivo. RESULTS: After nZn-CuO NPs
treatment, cell proliferation was significantly inhibited in dividing cancer
cells but less toxicity was observed in normal cells. In vivo studies show that
nZn-CuO NPs inhibited tumor growth in a dose-dependent manner. Further study
found that nZn-CuO NPs trigger cell reactive oxygen species (ROS) generation and
intrinsic apoptotic pathway. In temozolomide resistance glioblastoma, nZn-CuO NPs
disturb cell growth and sphere formation by inhibiting AKT and ERK1/2 activation.
CONCLUSION: nZn-CuO NPs possess the potential to be developed as a novel anti
tumor agent, especially to treat temozolomide resistance glioblastoma.
PMID- 29949470
TI - Toward biomedical application of amino-functionalized silicon nanoparticles.
AB - : Silicon blue-emitting nanoparticles (NPs) are promising effectors for
photodynamic therapy and radiotherapy, because of their production of reactive
oxygen species (ROS) upon irradiation. RESULTS: Amino-functionalized silicon NPs
(NH2SiNP) were intrinsically nontoxic below 100 MUg/ml in vitro (on two tumor
cell lines) and in vivo (zebrafish larvae and embryos). NH2SiNP showed a moderate
effect as a photosensitizer for photodynamic therapy and reduced ROS generation
in radiotherapy, which could be indicative of a ROS scavenging effect.
Encapsulation of NH2SiNP into ultradeformable liposomes improved their skin
penetration after topical application, reaching the viable epidermis where
neoplastic events occur. CONCLUSION: Subsequent derivatizations after amino
functionalization and incorporation to nanodrug delivery systems could expand the
spectrum of the biomedical application of these kind of silicon NPs.
PMID- 29949472
TI - Colloidal stability of superparamagnetic iron oxide nanoparticles in the central
nervous system: a review.
AB - Superparamagnetic iron oxide nanoparticles (SPIONs) consist of nanosized metallic
based particles with unique magnetic properties. Their potential in both
diagnostic and therapeutic applications in the CNS is at the source of an
expanding body of the literature in recent years. Colloidal stability of
nanoparticles represents their ability to resist aggregation and is a central
aspect for the use of SPION in biological environment such as the CNS. This
review gives a comprehensive update of the recent developments and knowledge on
the determinants of colloidal stability of SPIONs in the CNS. Factors leading to
aggregate formation and the repercussions of colloidal instability of SPION are
reviewed in detail pertaining to their use in the CNS.
PMID- 29949471
TI - Dose-, treatment- and time-dependent toxicity of superparamagnetic iron oxide
nanoparticles on primary rat hepatocytes.
AB - AIM: As a first study in literature, to investigate concentration-dependent (0
400 MUg/ml) and exposure-dependent (single dosing vs cumulative dosing) effects
of superparamagnetic iron oxide nanoparticles (d = 10 nm) on primary rat
hepatocytes in a time-dependent manner. MATERIALS & METHODS: Sandwich-cultured
hepatocyte model was used to evaluate viability, hepatocyte specific functions
and reactive oxygen species level. RESULTS: In terms of all parameters, generally
statistically more significant effects were observed in a concentration- and time
dependent manner. In terms of hepatocyte-specific functions, cumulative dosing
caused significantly (p < 0.05) more deleterious effects at 48th hour.
CONCLUSION: A combination of various biomarkers should be employed for the
evaluation of the effect of superparamagnetic iron oxide nanoparticles on liver,
and each biomarker should be analyzed in a time- and exposure-dependent manner.
PMID- 29949474
TI - Real Life After the Spotlight Fades.
PMID- 29949477
TI - At-home Bleaching With 10% vs More Concentrated Carbamide Peroxide Gels: A
Systematic Review and Meta-analysis.
AB - OBJECTIVE: To perform a systematic review to answer the following research
question: Is at-home bleaching in adults with more concentrated carbamide
peroxide (CP) gels as effective and safe as bleaching performed with 10%
carbamide peroxide gels? METHODS AND MATERIALS: A comprehensive search was
carried out in the MEDLINE via PubMed, Scopus, Web of Science, LILACS, BBO,
Cochrane Library and SIGLE, without restrictions. IADR abstracts (1990 to 2016)
and unpublished and ongoing trial registries, dissertations and theses (ProQuest
Dissertations and Periodicos Capes Theses Databases) were also searched. The risk
of bias of the included studies was analyzed using the Cochrane Risk of Bias tool
from the Cochrane Collaboration. We meta-analyzed the data using the random
effects model to compare 10% CP and more concentrated CP gels in terms of color
change (DeltaSGU or DeltaE) and risk and intensity of tooth sensitivity (TS). The
quality of the evidence was rated using the GRADE approach. RESULTS: After the
database screening, 182 articles remained, and this number was reduced to 17
after examination of the abstracts and/or full texts. Four articles were follow
ups of earlier studies, and thus we collected 13 studies. Ten studies were at
unclear risk of bias, while three were at low risk of bias. Lower risk and
intensity of TS was observed for 10% CP. The odds ratio for the risk of TS was
0.41 (95% CI 0.20 to 0.84, p=0.01), and the difference in means for TS intensity
was 0.44 (95% CI 0.67 to -0.20, p=0.0003). No significant difference was observed
in terms of color change in DeltaSGU (difference in means 0.29; 95% CI 0.25 to
0.83, p=0.29) and for DeltaE (difference in means -0.16; 95% CI 0.38 to 0.06,
p=0.16). Except from the DeltaSGU, for which the evidence was graded as low
quality, the other outcomes were considered at moderate quality. CONCLUSIONS: At
home bleaching with 10% CP showed similar bleaching efficacy with lower risk and
intensity of TS in comparison with more concentrated carbamide peroxide gels.
PMID- 29949478
TI - Influence of Thermal Stress on Simulated Localized and Generalized Wear of
Nanofilled Resin Composites.
AB - OBJECTIVE: This study investigated the influence of thermal stress on the
simulated localized and generalized wear of nanofilled resin composites. METHODS:
Six nanofilled resin composites were evaluated and then subjected to a wear
challenge of 400,000 cycles in a Leinfelder-Suzuki (Alabama) wear simulation
device after 24 hours of water storage (24-hour group) and 24 hours of water
storage and 10,000 thermal cycles (TC group). Simulated localized wear was
generated using a stainless-steel ball bearing, and simulated generalized wear
was generated using a flat-ended stainless-steel cylinder. Wear testing was
accomplished in a water slurry of polymethyl methacrylate beads. Simulated
localized and generalized wear was determined using a noncontact profilometer
(Proscan 2100) in conjunction with Proscan and AnSur 3D software. RESULTS: Wear
was significantly different ( p<0.05) among the resin composites for both
simulated localized and generalized wear of either the 24-hour group or the TC
group. The simulated localized wear of the TC group was significantly greater
than that of the 24-hour group; however, the simulated generalized wear of most
of the resin composites of the TC group was not significantly different from that
of the 24-hour group. CONCLUSION: The simulated localized and generalized wear of
nanofilled resin composites is material dependent. The simulated localized wear
of nanofilled resin composites appears to be influenced by thermal stress,
whereas this effect is not as apparent in simulated generalized wear testing.
PMID- 29949476
TI - Updates in Musculoskeletal Imaging.
PMID- 29949479
TI - Effectiveness of In-office Hydrogen Peroxide With Two Different Protocols: A Two
center Randomized Clinical Trial.
AB - OBJECTIVES: The aim of this study was to compare the bleaching efficacy and tooth
sensitivity (TS) of a 38% hydrogen peroxide bleaching agent used for in-office
bleaching, applied under different time protocols: a 40-minute application or two
20-minute applications. METHODS AND MATERIALS: Forty-four patients from Brazil
and Colombia, with right superior canines darker than C2, were selected for this
multicenter, single-blind, randomized trial. The teeth were bleached in two
sessions, with a one-week interval between them, in a split-mouth design. The
bleaching agent was applied in two 20-minute (2*20) applications or one 40-minute
(1*40) application in each session according to the manufacturer's instructions.
The color changes were evaluated by using subjective (Vita Classical and Vita
Bleachedguide) and objective (Easyshade Spectrophotometer) methods at baseline
and 30 days after the second session. Tooth sensitivity was recorded up to 48
hours with a 0-10 visual analog scale. Also, the pH values during the application
of bleaching were recorded. Color change in shade guide units and DeltaE were
analyzed by using the Student t-test (alpha=0.05). The absolute risk and
intensity of TS were evaluated with the McNemar test, the Wilcoxon signed-rank
test, and the Friedman test, respectively (alpha= 0.05). RESULTS: Significant
whitening was observed in both groups after 30 days of clinical evaluation. The
use of a 40-minute application did not significantly influence the absolute risk
of TS (68%, 95% confidence interval [CI] = 53-80) as well as the intensity of TS
compared with the acid bleaching gel (absolute risk of 82%, 95% CI = 68-91). The
pH values did not differ significantly between groups and at the different
assessment periods ( p=0.42). CONCLUSION: The use of a 40-minute in-office
bleaching agent gel application produced the same whitening degree and TS that
the two 20-minute bleaching agent applications did. The former preferably should
be applied because one 40-minute application does not require gel refreshing.
PMID- 29949481
TI - Online Only Articles.
AB - On occasion we receive manuscripts that we would like to publish, but do not have
the page room to include in the print journal. For the full article, please go to
www.jopdentonline.org or enter the provided address into your address bar.
PMID- 29949482
TI - Adrenal Calcifications in an Infant.
PMID- 29949483
TI - Case 20-2018: A 64-Year-Old Man with Fever, Arthralgias, and Testicular Pain.
PMID- 29949484
TI - Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection.
PMID- 29949473
TI - Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.
AB - BACKGROUND: Postpartum hemorrhage is the most common cause of maternal death.
Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but
it requires cold storage, which is not available in many countries. In a large
trial, we compared a novel formulation of heat-stable carbetocin with oxytocin.
METHODS: We enrolled women across 23 sites in 10 countries in a randomized,
double-blind, noninferiority trial comparing intramuscular injections of heat
stable carbetocin (at a dose of 100 MUg) with oxytocin (at a dose of 10 IU)
administered immediately after vaginal birth. Both drugs were kept in cold
storage (2 to 8 degrees C) to maintain double-blinding. There were two primary
outcomes: the proportion of women with blood loss of at least 500 ml or the use
of additional uterotonic agents, and the proportion of women with blood loss of
at least 1000 ml. The noninferiority margins for the relative risks of these
outcomes were 1.16 and 1.23, respectively. RESULTS: A total of 29,645 women
underwent randomization. The frequency of blood loss of at least 500 ml or the
use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4%
in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to
1.06), a finding that was consistent with noninferiority. The frequency of blood
loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the
oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence
interval crossing the margin of noninferiority. The use of additional uterotonic
agents, interventions to stop bleeding, and adverse effects did not differ
significantly between the two groups. CONCLUSIONS: Heat-stable carbetocin was
noninferior to oxytocin for the prevention of blood loss of at least 500 ml or
the use of additional uterotonic agents. Noninferiority was not shown for the
outcome of blood loss of at least 1000 ml; low event rates for this outcome
reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION
Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ;
EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number,
CTRI/2016/05/006969 .).
PMID- 29949485
TI - Inhaled Corticosteroids and LABAs - Removal of the FDA's Boxed Warning.
PMID- 29949486
TI - Change in Overweight from Childhood to Early Adulthood and Risk of Type 2
Diabetes.
PMID- 29949487
TI - Autoimmune Polyendocrine Syndromes.
PMID- 29949488
TI - Progress in Nonmetastatic Prostate Cancer.
PMID- 29949489
TI - Metastasis-free Survival - A New End Point in Prostate Cancer Trials.
PMID- 29949490
TI - Making Neighborhood-Disadvantage Metrics Accessible - The Neighborhood Atlas.
PMID- 29949491
TI - Personhood and the Three Branches of Government.
PMID- 29949492
TI - Combined Analysis of Asthma Safety Trials of Long-Acting beta2-Agonists.
AB - BACKGROUND: Safety concerns regarding long-acting beta2-agonists (LABAs) in
asthma management were initially identified in a large postmarketing trial in
which the risk of death was increased. In 2010, the Food and Drug Administration
(FDA) mandated that the four companies marketing LABAs for asthma perform
prospective, randomized, controlled trials comparing the safety of combination
therapy with a LABA plus an inhaled glucocorticoid with that of an inhaled
glucocorticoid alone in adolescents (12 to 17 years of age) and adults. In
conjunction with the FDA, the manufacturers harmonized their trial methods to
allow an independent joint oversight committee to provide a final combined
analysis of the four trials. METHODS: As members of the joint oversight
committee, we performed a combined analysis of the four trials comparing an
inhaled glucocorticoid plus a LABA (combination therapy) with an inhaled
glucocorticoid alone. The primary outcome was a composite of asthma-related
intubation or death. Post hoc secondary outcomes included serious asthma-related
events and asthma exacerbations. RESULTS: Among the 36,010 patients in the
intention-to-treat study, there were three asthma-related intubations (two in the
inhaled-glucocorticoid group and one in the combination-therapy group) and two
asthma-related deaths (both in the combination-therapy group) in 4 patients. In
the secondary analysis of serious asthma-related events (a composite of
hospitalization, intubation, or death), 108 of 18,006 patients (0.60%) in the
inhaled-glucocorticoid group and 119 of 18,004 patients (0.66%) in the
combination-therapy group had at least one composite event (relative risk in the
combination-therapy group, 1.09; 95% confidence interval [CI], 0.83 to 1.43;
P=0.55); 2100 patients in the inhaled-glucocorticoid group (11.7%) and 1768 in
the combination-therapy group (9.8%) had at least one asthma exacerbation
(relative risk, 0.83; 95% CI, 0.78 to 0.89; P<0.001). CONCLUSIONS: Combination
therapy with a LABA plus an inhaled glucocorticoid did not result in a
significantly higher risk of serious asthma-related events than treatment with an
inhaled glucocorticoid alone but resulted in significantly fewer asthma
exacerbations.
PMID- 29949493
TI - Case 5-2018: A Man with Confusion after Stem-Cell Transplantation.
PMID- 29949494
TI - Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer.
AB - BACKGROUND: Men with nonmetastatic, castration-resistant prostate cancer and a
rapidly rising prostate-specific antigen (PSA) level are at high risk for
metastasis. We hypothesized that enzalutamide, which prolongs overall survival
among patients with metastatic, castration-resistant prostate cancer, would delay
metastasis in men with nonmetastatic, castration-resistant prostate cancer and a
rapidly rising PSA level. METHODS: In this double-blind, phase 3 trial, we
randomly assigned, in a 2:1 ratio, men with nonmetastatic, castration-resistant
prostate cancer and a PSA doubling time of 10 months or less who were continuing
androgen-deprivation therapy to receive enzalutamide (at a dose of 160 mg) or
placebo once daily. The primary end point was metastasis-free survival (defined
as the time from randomization to radiographic progression or as the time to
death without radiographic progression). RESULTS: A total of 1401 patients
(median PSA doubling time, 3.7 months) underwent randomization. As of June 28,
2017, a total of 219 of 933 patients (23%) in the enzalutamide group had
metastasis or had died, as compared with 228 of 468 (49%) in the placebo group.
The median metastasis-free survival was 36.6 months in the enzalutamide group
versus 14.7 months in the placebo group (hazard ratio for metastasis or death,
0.29; 95% confidence interval, 0.24 to 0.35; P<0.001). The time to the first use
of a subsequent antineoplastic therapy was longer with enzalutamide treatment
than with placebo (39.6 vs. 17.7 months; hazard ratio, 0.21; P<0.001; such
therapy was used in 15% vs. 48% of patients) as was the time to PSA progression
(37.2 vs. 3.9 months; hazard ratio, 0.07; P<0.001; progression occurred in 22%
vs. 69% of patients). At the first interim analysis of overall survival, 103
patients (11%) receiving enzalutamide and 62 (13%) receiving placebo had died.
Adverse events of grade 3 or higher occurred in 31% of the patients receiving
enzalutamide, as compared with 23% of those receiving placebo. CONCLUSIONS: Among
men with nonmetastatic, castration-resistant prostate cancer with a rapidly
rising PSA level, enzalutamide treatment led to a clinically meaningful and
significant 71% lower risk of metastasis or death than placebo. Adverse events
were consistent with the established safety profile of enzalutamide. (Funded by
Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924 .).
PMID- 29949495
TI - Apalutamide and Metastasis-free Survival in Prostate Cancer.
PMID- 29949496
TI - Tongue Necrosis in Giant-Cell Arteritis.
PMID- 29949497
TI - Prophylaxis against Upper Gastrointestinal Bleeding in Hospitalized Patients.
PMID- 29949498
TI - Blastobotrys bombycis sp. nov., a d-xylose-fermenting yeast isolated from the gut
of the silkworm larva Bombyx mori.
AB - The gut of insects harbors a yeast community that is still poorly understood.
Here, a novel species of the ascomycetous genus Blastobotrys is proposed based on
a yeast strain isolated from the larval gut of the silkworm Bombyx mori (Order
Lepidoptera). The novel species is closely related to Blastobotrys aristata and
Blastobotrys elegans on the basis of the results of molecular phylogenetic
analyses. A preliminary screening revealed that it produces 1.5 g l-1 ethanol by
fermenting 5 % d-xylose. The novel species, that represents the first report, to
our knowledge, of yeast isolation from silkworms, is described as Blastobotrys
bombycis sp. nov. (type strain RAAB001T=CBS 15274T=PYCC 8105T=MCC 1427T; MycoBank
accession number MB 825095).
PMID- 29949499
TI - Ruegeria kandeliae sp. nov., isolated from the rhizosphere soil of a mangrove
plant Kandelia candel.
AB - A Gram-negative, rod-shaped and motile bacterium, designated strain J95T, was
isolated from the rhizosphere soil of a mangrove plant Kandeliacandel (L.) Druce
in Mai Po Nature Reserve, Hong Kong. Growth of strain J95T was observed at pH 5.0
8.5 (optimum, 6.0-7.0), between 10-40 degrees C (30-37 degrees C) and in the
presence of 0-9 % (w/v) NaCl (0.5-3 %). Chemotaxonomic analysis showed ubiquinone
10 as the predominant respiratory quinone and C18 : 1omega7c and C19 : 0
cycloomega8c as the major fatty acids. The major polar lipids were lipid,
aminolipid, phospholipid, phosphatidylcholine, phosphatidylglycerol and
phosphatidylethanolamine. The genomic contained a circular chromosome of 5.48 Mb
with a DNA G+C content of 65.7 mol%. The genome included 5299 genes. Phylogenetic
analysis based on 16S rRNA gene sequences indicated that strain J95T belongs to
the genus Ruegeria with highest sequence similarity (96.8 %) to the type strain
Ruegeria marina ZH17T. The combined phenotypic, chemotaxonomic and phylogenetic
data suggested that strain J95T represents a novel species of the genus Ruegeria,
for which the name Ruegeria kandeliae sp. nov. is proposed. The type strain is
J95T (=MCCC 1K03284T=DSM 104293T).
PMID- 29949500
TI - Shinella pollutisoli sp. nov., isolated from tetrabromobisphenol A-contaminated
soil.
AB - Strain AH-1T, a Gram-negative, aerobic, non-spore-forming, motile, rod-shaped
bacterium, was isolated from tetrabromobisphenol A-contaminated soil in China.
The taxonomic position was investigated using a polyphasic approach. Phylogenetic
analysis based on 16S rRNA gene sequences revealed that strain AH-1T was a member
of the genus Shinella and showed the highest sequence similarity to Shinella
fusca DC-196T (97.7 %), Shinella granuli Ch06T (97.3 %), Shinella daejeonensis
MJ02T (97.1 %) and Shinella yambaruensis MS4T (96.8 %), and lower (<96.7 %)
sequence similarity to other known Shinella species. Chemotaxonomic analysis
revealed that strain AH-1T possessed Q-10 as the major isoprenoid quinone; and
summed feature 8 (C18 : 1omega6c/C18 : 1omega7c), C16 : 0, C12 : 0 aldehyde, C18
: 0, C19 : 0 cyclo omega8c and C18 : 0 3-OH were the predominant fatty acids.
Strain AH-1T showed low DNA-DNA relatedness to S. fusca DC-196T (28.6+/-5.7 %),
S. granuli Ch06T (43.7+/-3.8 %) and S. daejeonensis MJ02T (48.1+/-2.6 %). The DNA
G+C content was 68.2 mol%. Based on the phylogenetic and phenotypic
characteristics, chemotaxonomic data and DNA-DNA hybridization, strain AH-1T is
considered a novel species of the genus Shinella, for which the name Shinella
pollutisoli sp. nov. (type strain AH-1T=KCTC 52677T=CCTCC AB 2017242T) is
proposed.
PMID- 29949501
TI - Variable regions of the glyS, infB and rplB genes usable as novel genetic markers
for identification and phylogenetic purposes of genera belonging to the family
Propionibacteriaceae.
AB - No common, unique genetic markers applicable to classification and phylogenetics
for significant genera within the Propionibacteriaceae family have been suggested
yet. Therefore, the aim of the study was to propose those genes in the genera
Acidipropionibacterium, Cutibacterium, Propionibacterium and
Pseudopropionibacterium. These genera were recently elicited from the genus
Propionibacterium through whole genomic analyses. Three housekeeping genes, glyS,
infB and rplB, were selected from many others according to the requirements for
appropriate classification/phylogenetic markers. Concrete fragments of the genes
were amplified using specific primers in most of the type (14) and 11 wild
strains (originating from dairy products, human skin and the crop of a laying
hen) recently classified into the genus Propionibacterium. Sequences obtained
from amplicons were used to perform gene statistics and phylogenetic analyses
with respect to applicability in classification, typing and phylogeny. The 16S
rRNA gene sequences, still considered relevant in spite of its proven
shortcomings as a basic tool for evaluation of bacterial phylogeny, were used as
a baseline for comparative analyses. The statistics of the gene sequences
revealed that the variable regions of all three genes have higher resolution
capabilities among strains examined compared to the 16S rRNA gene analysis.
Phylogenetic analyses based on individual gene sequences and their concatenate
enabled to distinguish clusters of species belonging to the genera
Acidipropionibacterium, Cutibacterium and Propionibacterium, which corresponds
with a recently reported genomic study. Thus, the crucial importance of this
study is the economically advantageous classification and typing of
propionibacterial isolates and strains through the three gene regions in contrast
to the requirement for whole genomic assays.
PMID- 29949502
TI - Therapeutic Doses of Eltrombopag do not Inhibit Hepatic BCRP in Healthy
Volunteers: Intravenous Ceftriaxone as a Model.
AB - PURPOSE: Ceftriaxone elimination occurs through breast cancer resistance
transporter (BCRP) and multidrug resistance-associated protein 2 (MRP-2) which
are expressed on the canalicular membrane of hepatocytes. Eltrombopag, a
thrombopoetin receptor agonist used in the treatment of immune thrombocytopenic
purpura, is reported in in vitro studies as an inhibitor of intestinal BCRP but
not an inhibitor of hepatic BCRP. Thus, the present study evaluates the effect of
therapeutic doses of eltrombopag on the clinical pharmacokinetics of intravenous
ceftriaxone. METHODS: Healthy adult (n=12) were treated with oral doses of
eltrombopag (0, 25 or 50 mg) 28 and 4 h prior to intravenous ceftriaxone
administration (1g). Serial blood samples were collected up to 48 h after
ceftriaxone administration and plasma samples were analysed by LC-MS/MS using 50
MUL aliquots (total concentration) and 100 MUL (unbound concentration). RESULTS:
A method to analyze total and unbound ceftriaxone in plasma using LC-MS/MS was
developed and validated with linearity from 1 to 200 MUg/mL. Both methods are
sensitive, precise and accurate with coefficients of variation less than 15% in
the study of inter- and intra-assay precision and accuracy. Ceftriaxone
pharmacokinetics in healthy adults were described using a bicompartmental model,
with a mean clearance of 0.96 L/h (CI95% 0.71-1.20) and AUC0-infinityof 1106
mg.h/mL (CI95% 811-1400) for volunteers that received only ceftriaxone; clearance
of 0.95 L/h (CI95% 0.77-1.13) and AUC0-infinity of 1083 mg.h/mL (CI95% 876-1290)
for volunteers that received ceftriaxone plus 25 mg of eltrombopag and clearance
of 0.96 L/h (CI95% 0.74-1.19) and AUC0-infinity of 1072 mg.h/mL (CI95% 872-1273)
for volunteers that received ceftriaxone plus 50 mg of eltrombopag. CONCLUSIONS:
The results do not support the existence of a clinical pharmacokinetic drug
interaction involving hepatic BCRP in human subjects receiving intravenous
ceftriaxone and oral eltrombopag. This article is open to POST-PUBLICATION
REVIEW. Registered readers (see "For Readers") may comment by clicking on
ABSTRACT on the issue's contents page.
PMID- 29949504
TI - Investigation of the mirrored-word reading paradigm for BCI implementation.
AB - Brain-computer interface (BCI) applications such as keyboard control and
vehicular navigation present significant assistive merit for disabled
individuals. However, there are limitations associated with BCI paradigms which
restrict a wider adoption of BCI technology. For example, rapid serial visual
presentation (RSVP) paradigms can induce seizures in photosensitive epileptic
subjects. This paper evaluates the novel mirrored-word reading paradigm (MWRP)
for BCI implementation using an offline experimental study. The offline study
obtained an average single-trial classification accuracy of 74.10%. The results
also demonstrate that the use of multiple trials for classification can increase
the accuracy as is common with BCIs. The developed MWRP-based BCI also utilized a
low presentation frequency which averts the possibility of paradigm induced
photosensitivity. However, there are multiple avenues for future work. The MWRP
can be implemented in the online format for real-time device control. For
example, a vehicular application platform can be used where the word orientation
represents directions for travel. The MWRP can also be investigated across a
wider range of stimulus presentation parameters such as timing, color and
stimulus size. Such studies can be used to suggest further improvements to the
paradigm which can enhance its applicability for online device control.
PMID- 29949503
TI - Multimodal cell tracking from systemic administration to tumour growth by
combining gold nanorods and reporter genes.
AB - Understanding the fate of exogenous cells after implantation is important for
clinical applications. Preclinical studies allow imaging of cell location and
survival. Labelling with nanoparticles enables high sensitivity detection, but
cell division and cell death cause signal dilution and false positives. By
contrast, genetic reporter signals are amplified by cell division. Here, we
characterise lentivirus-based bi-cistronic reporter gene vectors and silica
coated gold nanorods (GNRs) as synergistic tools for cell labelling and tracking.
Co-expression of the bioluminescence reporter luciferase and the optoacoustic
reporter near-infrared fluorescent protein iRFP720 enabled cell tracking over
time in mice. Multispectral optoacoustic tomography (MSOT) showed immediate
biodistribution of GNR-labelled cells after intracardiac injection and successive
clearance of GNRs (day 1-15) with high resolution, while optoacoustic iRFP720
detection indicated tumour growth (day 10-40). This multimodal cell tracking
approach could be applied widely for cancer and regenerative medicine research to
monitor short- and long-term biodistribution, tumour formation and metastasis.
PMID- 29949505
TI - Evaluation of a new non-invasive measurement technique based on bioimpedance
spectroscopy to estimate blood alcohol content: a pilot study.
AB - The gold standard for estimating blood alcohol content (BAC) after alcohol
consumption is a blood sample analysis. An innovative technology to estimate BAC
is based on impedance cardiography and bioimpedance spectroscopy (BIS). This
study investigated whether it is possible to estimate increasing blood alcohol
levels during a drinking trial with bioimpedance measurement techniques. Twenty
one healthy volunteers were assigned to a test (ethanol) group (ETH) or a
reference group (H2O). After baseline measurements, the ETH group ingested 120 ml
of vodka, followed by a resorption phase of 50 min. Then, bioimpedance and breath
alcohol measurements were performed. Thereafter, 60 ml of vodka was ingested and
another resorption phase of 50 min was followed by bioimpedance and breath
alcohol measurements. This procedure was repeated until alcohol levels exceeded
0.4 mg/l. The H2O group performed in the same way with water. For all
measurements, extracellular resistance (Re) and the base impedance (Z0) were
computed. Regarding BIS, several parameters differed significantly between the
ETH and the H2O group. Re increased in ETH (p=0.005), but not in the H2O group
when comparing the first and last measurements. Z0 also increased significantly
in the ETH group (p=0.001). To conclude, with BIS measurements, it is possible to
measure increasing blood alcohol levels.
PMID- 29949506
TI - Increased serum concentrations of soluble ST2 predict mortality after burn
injury.
AB - BACKGROUND: Large burn injuries induce a systemic response in affected patients.
Soluble ST2 (sST2) acts as a decoy receptor for interleukin-33 (IL-33) and has
immunosuppressive effects. sST2 has been described previously as a prognostic
serum marker. Our aim was to evaluate serum concentrations of sST2 and IL-33
after thermal injury and elucidate whether sST2 is associated with mortality in
these patients. METHODS: We included 32 burn patients (total body surface area
[TBSA] >10%) admitted to our burn intensive care unit and compared them to eight
healthy probands. Serum concentrations of sST2 and IL-33 were measured serially
using an enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: The mean
TBSA was 32.5%+/-19.6%. Six patients (18.8%) died during the hospital stay. Serum
analyses showed significantly increased concentrations of sST2 and reduced
concentrations of IL-33 in burn patients compared to healthy controls. In our
study cohort, higher serum concentrations of sST2 were a strong independent
predictor of mortality. CONCLUSIONS: Burn injuries cause an increment of sST2
serum concentrations with a concomitant reduction of IL-33. Higher concentrations
of sST2 are associated with increased in-hospital mortality in burn patients.
PMID- 29949508
TI - Uncertainty in measurement and total error: different roads to the same quality
destination?
AB - The debate comparing the benefits of measurement uncertainty (uncertainty in
measurement, MU) with total error (TE) for the assessment of laboratory
performance continues. The summary recently provided in this journal by members
of the Task and Finish Group on Total Error (TFG-TE) of the EFLM put the
arguments into clear perspective. Even though there is generally strong support
for TE in many laboratories, some of the arguments proposed for its on-going
support require further comment. In a recent opinion which focused directly on
the TFG-TE summary, several potentially confusing statements regarding ISO15189
and the Evaluation of measurement data - Guide to the expression of uncertainty
in measurement (GUM) were again promulgated to promote TE methods for assessing
uncertainty in laboratory measurement. In this opinion, we present an alternative
view of the key issues and outline our views with regard to the relationship
between ISO15189, uncertainty in measurement and the GUM.
PMID- 29949507
TI - Commutability of the certified reference materials for the standardization of
beta-amyloid 1-42 assay in human cerebrospinal fluid: lessons for tau and beta
amyloid 1-40 measurements.
AB - BACKGROUND: The core Alzheimer's disease cerebrospinal fluid (CSF) biomarkers
total tau (T-tau), phosphorylated tau (P-tau), beta-amyloid 1-42 (Abeta42) and
beta-amyloid 1-40 (Abeta40) are increasing in importance and are now part of the
research criteria for the diagnosis of the disease. The main aim of this study is
to evaluate whether a set of certified reference materials (CRMs) are commutable
for Abeta42 and to serve as a feasibility study for the other markers. This
property is a prerequisite for the establishment of CRMs which will then be used
by manufacturers to calibrate their assays against. Once the preanalytical
factors have been standardized and proper selection criteria are available for
subject cohorts this harmonization between methods will allow for universal cut
offs to be determined. METHODS: Thirty-four individual CSF samples and three
different CRMs where analyzed for T-tau, P-tau, Abeta42 and Abeta40, using up to
seven different commercially available methods. For Abeta40 and Abeta42 a mass
spectrometry-based procedure was also employed. RESULTS: There were strong
pairwise correlations between the different methods (Spearman's rho>0.92) for all
investigated analytes and the CRMs were not distinguishable from the individual
samples. CONCLUSIONS: This study shows that the CRMs are commutable for the
different assays for Abeta42. For the other analytes the results show that it
would be feasible to also produce CRMs for these. However, additional studies are
needed as the concentration interval for the CRMs were selected based on Abeta42
concentrations only and did in general not cover satisfactory large concentration
intervals for the other analytes.
PMID- 29949509
TI - Interruptions, work environment and work load perceptions in laboratory medicine:
patient safety is a "moving target".
PMID- 29949510
TI - The Model List of Essential In Vitro Diagnostics: nuisance or opportunity?
PMID- 29949511
TI - Blister-packed levothyroxine sodium or bottle-packed levothyroxine sodium.
PMID- 29949512
TI - Screening for autoimmune thyroiditis and celiac disease in minority children with
type 1 diabetes.
AB - BACKGROUND: Hashimoto's thyroiditis (HT) and celiac disease (CD) are commonly
associated with type 1 diabetes (T1DM). There is no consensus on screening,
however, the American Diabetes Association (ADA) and the International Society
for Pediatric and Adolescent Diabetes (ISPAD) recommend testing for thyroid
function (TFT), thyroid antibodies and anti-tissue transglutaminase antibodies
(TTG) IgA soon after diagnosis. TFT should be repeated every 1-2 years while TTG
IgA should be tested for within 2 and 5 years. We hypothesize that the rate of HT
and CD in our T1DM children is lower, so screening may need to be revised to
reflect their underlying risk. METHODS: An Institutional Review Board (IRB)
approved retrospective chart review was conducted on children with T1DM in the
past 10 years. Age, sex, race, A1C, TFT, thyroid and celiac antibodies were
obtained. t-Tests, the Wilcoxon-Mann-Whitney test and stepwise regression were
performed. RESULTS: Of 222 children with T1DM, with a mean age of 15.8+/-5.53
years, followed for 6.1+/-4.0 years, 53% female, mean A1C 11.1+/-1.9% and 87%
African American (AA). Three had Graves' disease (1.3%), three had HT (1.3%) and
97% were euthyroid. TFT were assessed on average every 1.3 years and thyroid
antibodies every 2.5 years. Positive thyroid antibody was found in 11%, negative
in 57% and unknown in 32%. The positive antibody group had higher mean A1C and
TSH. No biopsy confirmed cases of CD (0%) were found when screened every 2.3
years. CONCLUSIONS: The number of individuals who screened positive for
hypothyroid HT and CD was lower than expected in our population. Further studies
are needed to assess the optimal screening frequency for HT and CD in minority
children with T1DM.
PMID- 29949513
TI - Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical
heterogeneity and long-term efficacious management of eight patients from four
unrelated Arab families with a loss of function VDR mutation.
AB - BACKGROUND: Vitamin D regulates the concentrations of calcium and phosphate in
blood and promotes the growth and remodeling of bones. The circulating active
form of vitamin D, 1,25-dihydroxyvitamin D, binds to the vitamin D receptor
(VDR), which heterodimerizes with the retinoid X receptor to regulate the
expression of target genes. Inactivating mutations in the VDR gene cause
hereditary vitamin D-resistant rickets (HVDRR), a rare disorder characterized by
an early onset of rickets, growth retardation, skeletal deformities,
hypocalcemia, hypophosphatemia and secondary hyperparathyroidism, and in some
cases alopecia. METHODS: We describe eight new HVDRR patients from four unrelated
consanguineous families. The VDR gene was sequenced to identify mutations. The
management of patients over a period of up to 11 years following the initial
diagnosis is assessed. RESULTS: Although all patients exhibit main features of
HVDRR and carry the same c.885C>A (p.Y295*) loss of function mutation in the VDR
gene, there was heterogeneity of the manifestations of HVDRR-associated
phenotypes and developmental milestones. These eight patients were successfully
treated over a period of 11 years. All clinical symptoms were improved except
alopecia. CONCLUSIONS: The study concludes that VDR sequencing and laboratory
tests are essential to confirm HVDRR and to assess the effectiveness of the
treatment.
PMID- 29949514
TI - Thromboprophylaxis in pregnant women with thrombophilia and a history of
thrombosis.
AB - Background Despite intensive research, thromboembolism still accounts for
significant maternal morbidity and mortality. We examined thrombophilia in
patients with thromboembolism during pregnancy and evaluated the efficiency of
antithrombotic prophylaxis in patients with thrombophilia for the prevention of
recurrent thromboembolism. Materials and methods Sixty-eight women with a history
of thromboembolism were managed during pregnancy, in light of their thrombotic
history and the result of thrombophilia assessment. Group I (n=50) received
prophylaxis with low molecular weight heparin (LMWH)+/-aspirin (50-100 mg/day) in
preconception period or from the 1st trimester, during pregnancy and at least 6
weeks postpartum. Group II (n=18) received LMWH+/-aspirin from the II to III
trimester. Results Thromboses were associated with pregnancy in 27 patients
(39.7%), with systemic diseases - in nine (13.2%), oral contraceptives use - 22
(32.3%), immobilization due to surgery and/or trauma, long flight - six (8.9%),
septic complications - two (2.9%). Nevertheless, 24.5% of patients had no
apparent provoking factor for the development of thrombotic complications. Thirty
seven (54%) patients with venous thromboembolism (VTE) had familial history of
VTE, and 25 (36.7%) had personal history of pregnancy complications (fetal loss
syndrome, preeclampsia and placental abruption) (P<0.05 vs. control).
Thrombophilia was detected in 58 (85.3%). Usual thrombogenic polymorphisms
[factor V (FV) Leiden and prothrombin G20210A, heterozygous forms] were revealed
in 16 (23.5%) and eight (11.7%) patients, respectively. Antiphospholipid
antibodies (aPL) circulation was found in 34 (50%) patients. Non-usual
thrombogenic polymorphisms were identified in 44 (64.7%) of the women and
hyperhomocysteinemia - in 30 (44.2%). In group I no one had severe obstetric
complications. All the patients were delivered at term and all the babies were
alive. In group II moderate-to-severe obstetric complications were noted:
preeclampsia - in 11 (16.2%), severe preeclampsia - seven (10.3%), preterm
delivery - in 18 (26.4%) patients from subgroup II (P<0.05). Conclusions Women
with a personal or a family history of thromboembolism and obstetric
complications should be screened for thrombophilia. Beginning anticoagulant
therapy early in such patients is effective not only for preventing recurring
thrombosis but also preventing obstetric complications. Late prophylaxis after
the completion of the trophoblast invasion therapy is much less effective.
PMID- 29949515
TI - Growth and body composition in preterm newborns with bronchopulmonary dysplasia:
a cohort study.
AB - : Objective To compare growth and body composition of preterm infants
(gestational age <32 weeks) with and without bronchopulmonary dysplasia (BPD).
Methods A prospective cohort involving three neonatal units in the public health
system of the Brazilian city of Rio de Janeiro. Inclusion: newborns with
gestational age <32 weeks. EXPOSURE: BPD. Anthropometric measurements were
performed at birth and at 1 month of infant corrected age. Body composition was
measured using an air displacement plethysmography (ADP) (PEA POD(r)) at 1 month
of infant corrected age. Results Ninety-five newborns were eligible, of which 67
were included, 32.8% of them with BPD. Newborns with BPD presented lower
gestational age at birth, greater need for resuscitation in the delivery room,
received parenteral nutrition (PN) for a longer period of time, achieved lower
weights during hospital stay and required more time to reach a full enteral diet.
No statistically significant differences were observed in relation to
anthropometric measurements and body composition at 1 month of infant corrected
age between the groups with and without BPD. Conclusion This study, unlike
previous ones, has shown that children who developed BPD were able to regain
growth, as measured by anthropometric measures, with no change in body
composition at 1 month of infant corrected age.
PMID- 29949516
TI - Ductus venosus agenesis and fetal malformations: what can we expect? - a
systematic review of the literature.
AB - OBJECTIVES: The ductus venosus agenesis (DVA) is a rare condition with a variable
prognosis that relies partly on the presence of associated conditions. The
purpose of our study was to analyze the literature regarding the post-natal
outcome of fetuses with DVA associated with fetal malformations, in order to
discuss the best management options for couples. DATA SOURCES: We performed a
systematic review of the literature of MEDLINE and SCOPUS electronic databases in
a 25-year period from 1992 to September 2017. RESULTS: We found 340 cases of DVA
associated with fetal abnormalities. The most common chromosomal abnormalities
were: monosomy X (12/48, 25%), trisomy 21 (11/48, 22.9%) and trisomy 18 (6/48,
12.5%). From the 340 cases with DVA, in 31 cases the umbilical venous shunt type
was not reported. Of the fetuses, 60.8% (188/309) had an extrahepatic umbilical
venous drainage while 39.2% (121/309) presented an intrahepatic connection. The
DVA was associated in 71 cases (23.0%) with cardiac abnormalities, in 82 cases
(26.5%) with extracardiac abnormalities and in 85 cases (27.5%) with both cardiac
and extracardiac abnormalities. CONCLUSION: DVA associated with both cardiac and
extracardiac malformations may confer a poorer fetal outcome, a clinically
relevant fact that should clarify what can be expected from this entity and help
prenatal counseling.
PMID- 29949517
TI - Colored body images reveal the perceived intensity and distribution of pain in
women with breast cancer treated with adjuvant taxanes: a prospective multi
method study of pain experiences.
AB - Background and aims Breast cancer is the most prevalent adult cancer worldwide. A
broader use of screening for early detection and adjuvant systemic therapy with
chemotherapy has resulted in improved survival rates. Taxane-containing
chemotherapy is one of the cornerstones of the treatment. However, taxane
containing chemotherapy may result in acute chemotherapy-induced nociceptive and
neuropathic pain. Since this pain may be an additional burden for the patient
both during and after taxane chemotherapy, it is important to rapidly discover
and treat it. There is yet no gold standard for assessing taxane-induced pain. In
the clinic, applying multiple methods for collecting information on pain may
better describe the patients' pain experiences. The aim was to document the pain
during and after taxane through the contribution of different methods for
collecting information on taxane-induced pain. Fifty-three women scheduled for
adjuvant sequential chemotherapy at doses of >=75 mg/m2 of docetaxel and
epirubicin were enrolled in the study. Methods Prospective pain assessments were
done on a visual analog scale (VAS) before and during each cycle of treatment for
about 5 months, and using the European Organization for Research and Treatment of
Cancer Quality of Life Questionnaire's (EORTC-QLQ-C30) two pain questions at
baseline, 3 months, and 12 months. Participants scoring pain on the VAS >30 and
undergoing an interview also colored their pain on a body image during treatment
and at 12 months. Results Surprisingly widespread, intense pain was detected
using a multi-method approach. The colored body image showed pain being perceived
on 51% of the body surface area during treatment, and on 18% 12 months after
inclusion. In general, the pain started and peaked in intensity after the first
cycle of taxane. After Cycle 3, most women reported an increase in pain on the
VAS. Some women continued to report some pain even during the epirubicin cycles.
The VAS scores dropped after the last chemotherapy cycle, but not to the baseline
level. At baseline, 3 months and 12 months after inclusion, the women who
estimated VAS >30 reported higher levels of pain on the pain questions of the
EORTC-QLQ-C30. Conclusions This study contributes information on how different
pain assessment tools offer different information in the assessment of pain. The
colored body image brings another dimension to pain diagnostics, providing
additional information on the involved body areas and the pain intensities as
experienced by the women. A multi-method approach to assessing pain offers many
advantages. The timing of the assessment is important to properly assess pain.
Implications Pain relief needs to be included in the chemotherapy treatment, with
individual assessment and treatment of pain, in the same way as is done in
chemotherapy-triggered nausea. There is a time window whereby the risk of pain
development is at its highest within 24-48 h after receiving taxane chemotherapy.
Proper attention to pain evaluation and treatment should be in focus during this
time window.
PMID- 29949518
TI - Physiotherapy pain curricula in Finland: a faculty survey.
AB - Background and aims Despite the recognition of pain as a global health problem
and advancements achieved in what is known about effective pain management, pain
education for undergraduate health care professionals remains insufficient. This
study investigated the content of pain curricula and the time allocated to pain
education on physiotherapy programs at bachelor's level at Universities of
Applied Sciences (UASs) in Finland. Methods A web-based survey questionnaire was
sent to the directors of the physiotherapy programs at all the Finnish UASs
(n=15) where physiotherapy is taught at bachelor's level. The questionnaire
consisted of 14 questions covering basic concepts and the science of pain, pain
assessment, pain management, and the adequacy of pain curricula. Each UAS
completed one questionnaire i.e. returned one official opinion. Results The
response rate was 80% (n=12). The mean for the total number of contact hours of
pain education was 74 (standard deviation 34.2). All UASs had integrated pain
education. In addition to this 42% (n=5) of the UASs had a separate pain course.
The UASs offering such a course over and above the integrated pain education had
twice the amount of pain content education compared to those UASs that only had
integrated pain education (mean 103 h vs. 53 h, p=0.0043). Most of the education
was devoted to conditions where pain is commonly a feature, manual therapy, and
electrical agents for pain control. The biopsychosocial model of pain, cognitive
behavioral methods of pain management, physician management, and
multidisciplinary management were the least covered topics. Five UASs (42%) payed
attention to the International Association for the Study of Pain curriculum
outline and only 33% (n=4) considered their pain education to be sufficient.
Conclusions Our results indicate that more contact hours are devoted to pain
education on the Finnish UASs' physiotherapy programs at bachelor's level, than
has previously been reported in faculty surveys. A separate pain course is one
way to ensure a sufficient amount of pain education. Overall, despite a
sufficient time devoted to pain education, some essential pain contents were
inadequately covered. Implications The study contributes information on how pain
education can be organized on physiotherapy programs at undergraduate level.
Besides a sufficient amount of pain education, which can be ensured by a separate
pain course, attention should be paid to pain education content being up-to-date.
This could help in estimating the different proportions of pain content needed in
educational settings. Efforts should also be made at keeping integrated pain
education well-coordinated and purposeful. There is a need for further research
estimating the effectiveness of pain education according to the different ways in
which it is organized. There is also a need to investigate whether more hours
allocated to pain education results in better understanding and professional
skills.
PMID- 29949519
TI - Laser-induced transformation of graphitic materials to two-dimensional graphene
like structures at ambient conditions.
AB - Laser processing of carbon compounds towards the formation of graphene-based
structures gains ground in view of the practicality that lasers offer against
other conventional graphene preparation methods. The current work explores the
viability of low-cost lasers, operating at ambient conditions, for the
transformation of various graphitic materials to structures with graphene-like
atomic arrangements. Starting materials are at two opposing sides. On one side
stands the typical graphite crystal with Bernal stacking and strong sp 2
character, while nanocrystalline graphitic powders are also investigated. It is
demonstrated that graphene-like structures can be prepared either by starting
from a well-organized Bernal-stacked network or by irradiating nanocrystalline
carbon. The current findings document that laser processing at minimal chamber
conditions shows high potential for preparing high-quality graphene-based
structures starting from low-cost materials. Apart from being scalable, the
proposed method is adaptable to current technological platforms emerging as a
viable and eco-friendly graphene production technology.
PMID- 29949520
TI - The effect of DNA on the oxidase activity of nanoceria with different
morphologies.
AB - Many nanomaterials have been reported to have enzyme-like activities and are
considered as nanozymes. As a multifunctional nanozyme, nanoceria has received
much attention due to the dual oxidation states of Ce3+/Ce4+ which facilitate
redox reactions at the particle surface. Despite the advantages of nanozymes,
their limited activity and lack of enzyme specificity are still problems to be
resolved. DNA is used to modulate the oxidase activity of nanoceria because it
has recently become an important molecule in bionanotechnology. However, the
current research on the effect of DNA on the oxidase mimetic activity of
nanoceria is contradictory. It has been discovered that nanoceria used in recent
works are different, including in particle size, doping and concentration, and
these differences may affect the interaction between DNA and nanoceria, and then
affect the oxidase mimetic activity of nanoceria. Hence, it is important to
clarify the factors that affect the interaction between DNA with nanoceria. In
this work, the interactions between DNA and nanoceria with three different
morphologies (nanoparticles, nanocubes, and nanorods) have been investigated.
Experimental results show that DNA has different influences on the oxidase
mimetic activity of nanoceria with different morphologies. The oxidase mimetic
activity of CeO2 nanoparticles and nanocubes increased, but that of CeO2 nanorods
decreased, after DNA modification. The mechanism of these experimental results
has been explored, and it has been found that it is the interaction between
cerium and the phosphate backbone of DNA that changes with the different
morphologies, resulting in the varying effect of DNA on the oxidase mimetic
activity of nanoceria. These results may provide a better understanding of the
effect of DNA on the oxidase mimetic activity of nanoceria and promote the
applications of nanoceria.
PMID- 29949521
TI - Respiratory-resolved MR-based attenuation correction for motion-compensated
cardiac PET-MR.
AB - Respiratory motion during cardiac PET acquisitions can cause image blurring and
erroneous uptake quantification. In particular the misalignment of attenuation
correction (AC) maps and PET emission data can lead to severe quantification
errors, because the AC value of the heart is five times higher than of the
surrounding lung tissue. Standard PET-MR approaches assume accurate alignment
between breathhold MR-based AC maps and free-breathing PET emission data but
cannot necessarily ensure it. Here we propose a 75 s free-breathing MR
acquisition, which provides respiratory-resolved AC maps (ACDyn) and non-rigid
respiratory motion information. This approach ensures accurate AC for free
breathing PET data and the motion information can be utilized to reduce image
blurring caused by respiratory motion. 3D multi-echo MR data was acquired during
a 75 s free-breathing scan in six patients. Both a respiratory-resolved dynamic
AC map (ACDyn) and a non-rigid respiratory motion field are provided by the MR
scan. ACDyn yielded AC values for different breathing phases ensuring accurate AC
for each respiratory phase of the free-breathing PET data. In addition, motion
corrected image reconstruction (MCIR) of MR and PET data was used to minimize
breathing artefacts. Motion amplitudes in the left ventricle were 8.2 +/- 2.9
mm with a dominant motion direction along the anterior-anterolateral and inferior
inferoseptal axis of the heart. The proposed ACDyn-MCIR technique led to
significant signal recovery of PET tracer uptake by 24 +/- 5% (p < 0.05). The
maximum improvement was observed in patients with large misalignment between
standard breathhold MR-based AC maps and PET emission data. PET image resolution
was improved by 20 +/- 12% (p < 0.05). We have presented an efficient MR
scan, which ensures accurate motion information and AC values to improve PET
quantification for cardiac PET-MR scans. The short scan time of 75 s makes this
free-breathing acquisition easy to integrate into standard clinical PET-MR
protocols.
PMID- 29949522
TI - Physico-chemical investigation of ZnS thin-film deposited from ligand-free
nanocrystals synthesized by non-hydrolytic thio-sol-gel.
AB - Ultra-small and monodispersed zinc sulfide nanocrystals (NCs) (d <= 3 nm) have
been prepared without the use of any surfactants by a synthetic route using
benzyl mercaptan as a source of sulfur. The prepared NCs are dispersible in
highly polar solvents and display the capability to closely pack-up in a bulky
film. The NCs were characterized by TEM, XRD and UV-vis optical absorption as
well as by steady-state and time-resolved photoluminescence (PL) spectroscopies.
Uniform films of ZnS were spin-coated on glass and ITO-glass substrates using a
NCs dispersion in N,N-dimethylformamide. The NCs and the resulting films were
characterized by morphological and optoelectronic probing techniques such as AFM,
SEM, diffuse reflectance, PL and photoelectron spectroscopy in air. These
physical investigations confirmed that the chalcogenide NCs grown by this method
have the potential to be utilized directly as photocatalysts and are potentially
useful building-blocks/starting materials for the fabrication of semiconductor
thin films for optoelectronic applications such as LED, luminescent screens,
field effect transistor and solar cells. Insights on the chemistry involved in
the NCs growth have been provided revealing that their formation proceeds through
a mechanism involving a thioether elimination reaction.
PMID- 29949523
TI - Reconfigurable logic in nanosecond Cu/GeTe/TiN filamentary memristors for energy
efficient in-memory computing.
AB - Owing to the capability of integrating the information storage and computing in
the same physical location, in-memory computing with memristors has become a
research hotspot as a promising route for non von Neumann architecture. However,
it is still a challenge to develop high performance devices as well as optimized
logic methodologies to realize energy-efficient computing. Herein, filamentary
Cu/GeTe/TiN memristor is reported to show satisfactory properties with nanosecond
switching speed (<60 ns), low voltage operation (<2 V), high endurance (>104
cycles) and good retention (>104 s @85 degrees C). It is revealed that the
charge carrier conduction mechanisms in high resistance and low resistance states
are Schottky emission and hopping transport between the adjacent Cu clusters,
respectively, based on the analysis of current-voltage behaviors and resistance
temperature characteristics. An intuitive picture is given to describe the
dynamic processes of resistive switching. Moreover, based on the basic material
implication (IMP) logic circuit, we proposed a reconfigurable logic method and
experimentally implemented IMP, NOT, OR, and COPY logic functions. Design of a
one-bit full adder with reduction in computational sequences and its validation
in simulation further demonstrate the potential practical application. The
results provide important progress towards understanding of resistive switching
mechanism and realization of energy-efficient in-memory computing architecture.
PMID- 29949525
TI - OX40L gene polymorphism and breast cancer in Iranian population.
AB - BACKGROUND AND AIM: The immune system plays an important role in the breast
cancer development. OX40L (also known as TNFSF4), a membrane protein, which is a
member of the tumor necrosis factor super family binds to its receptor OX40 and
this co-stimulation has a crucial role in T cell proliferation, survival and
cytokine release. Previous studies have shown that OX40L is associated with
cancer. Due to the importance of the T cells in antitumor activities of OX40L we
studied the association of rs3850641 (A->G) polymorphism of OX40L gene with the
breast cancer. MATERIALS AND METHODS: The study included 123 women with breast
cancer and 126 healthy volunteers with no signs of cancer. Genomic DNA was
extracted from blood leucocytes. Genotype and allele frequencies were determined
in patients and control cases with the method of polymerase chain reaction
restriction fragment length polymorphism and the statistical analysis was
performed by Med Calc. RESULTS: The prevalence of genotype frequencies of
AA/AG/GG were 60.9%, 30.08% and 8.9% in patients with breast cancer cases and
74.6%, 18.25% and 7.14% in healthy volunteers while the A and G allelic frequency
was 76.01 and 23.98% in patients and 83.73 and 16.26% in healthy controls,
respectively. Statistical analysis has shown significant difference from the
comparison of genotype (p = 0.03). CONCLUSION: It is concluded that the rs3850641
SNP is significantly associated with the breast cancer susceptibility in Iranian
population. However, further studies in larger populations including other
genetic and environmental factors are required to achieve conclusion.
PMID- 29949524
TI - Pentraxin-3 in Thrombolytic Therapy for Acute Ischemic Stroke: No Relation with
Curative Effect and Prognosis.
AB - BACKGROUND Pentraxin-3 (PTX3) is considered a high quality inflammatory marker of
the severity and prognosis of several diseases, however, the value of PTX3 in
thrombolytic therapy for acute ischemic stroke remains unclear and PTX3 is still
controversial in evaluating the prognosis of stroke patients. In this study, we
investigated the association of PTX3 with thrombolytic therapy in patients with
acute ischemic stroke. MATERIAL AND METHODS Forty-seven stroke patients who
received thrombolytic therapy within 4.5 hours after symptom onset were enrolled
consecutively between July 2016 and June 2017. All the patients underwent
multiphase CTA (computerized tomography angiography) or CT perfusion before
thrombolysis with no indication for endovascular treatment. Initial and 24 hours
of National Institute of Health Stroke Scale (NIHSS) scores and serum PTX3 level,
stroke risk factors and predictors, and mRS (modified Rankin scale) at 3 months
were collected prospectively. Predictors of thrombolytic therapy effect and long
term prognosis were investigated by univariate and multivariate logistic
regression. RESULTS The 24 hour NIHSS score and the treatment time was associated
with symptom improvement, while the PTX3 level had no association with
neurological improvement and prognosis in stroke patients receiving thrombolytic
therapy. CONCLUSIONS PTX3 is not suitable to serve as an indicator of
thrombolytic efficacy and had no association with long-term prognosis in stroke
patients receiving thrombolytic therapy.
PMID- 29949526
TI - The state of bone metabolism in lung cancer patients.
AB - : In recent years, we have discussed the correlation of malignant tumor process
with the development of osteoporosis, which can be exacerbated by ongoing
chemotherapy and radiation therapy. The aim of the work was to assess the status
of bone metabolism in 32 untreated patients with lung cancer without metastasis.
MATERIALS AND METHODS: Patients underwent dual-energy X-ray osteodensitometry of
proximal part of femoral bone. Osteopontin (OP), osteocalcin (OC) and alkaline
phosphatase (AP) parameters were studied in blood, as well as osteo-associated
chemical elements. RESULTS: Lung cancer proceeds with severe disorders of bone
metabolism, which is accompanied by an increase in blood levels of OP, OS, AP,
phosphorus, lithium, lead, strontium and cobalt against a decrease of calcium,
magnesium and manganese, which were observed in 75; 78; 31; 100; 66; 47; 44; 3;
100; 100, and 6% of patients, respectively; such disorder was associated with a
morphological variant of the tumor (cobalt) and stage of disease (calcium,
magnesium, manganese, strontium), development of osteodeficit (OP, OC, AR,
strontium, zinc). Osteodeficit in the form of osteopenia and osteoporosis is
observed more common in women, in every second patient, and osteodensimetric T
score depends on the age of patients, directly correlates with the values of the
OP and OC, and inversely - with a zincemia rate. CONCLUSIONS: The disorders of
bone metabolism in patients with lung cancer indicate the need for the
development of antiosteoporosis treatment for cancer patients.
PMID- 29949527
TI - Intersection between genes controlling vascularization and angiogenesis in renal
cell carcinomas.
AB - AIM: To show that application of the systemic analysis may significantly improve
comparison of different datasets. Different genes and proteins may converge on
the same functional outputs. A comparison of 2 datasets by only identification
names of affected molecules may miss that, leading to a conclusion that there is
nothing in common for these datasets. Systemic analysis may overcome this
limitation, by focusing on functions represented by the identification names.
MATERIALS AND METHODS: Datasets were retrieved from open sources. Systemic
analysis of vascularization features and angiogenesis signature was performed by
using Cytoscape and its plugs-in. RESULTS: In contrary to the initial statement
of the lack of overlap between the vascularization features and the angiogenesis
genes-signature in renal carcinomas, we observed an intersection on the
functional level. Analysis of the networks built with identification names of
vascularization and angiogenesis datasets showed an intersection, which included
potent regulators of vessel formation and growth. CONCLUSION: Analysis of
networks may expose functional links, which may be missed by a direct
identification names comparison.
PMID- 29949528
TI - Clinical case of a patient undergoing radium-223 treatment following treatment
with abiraterone acetate and enzalutamide.
AB - OBJECTIVE: Over the last decade, significant advances have been made in the
development of therapies for patients with metastatic castration-resistant
prostate cancer. Abiraterone and enzalutamide were approved as treatments based
on data supporting improved overall survival compared to placebo. Radium-223
became the first approved radiopharmaceutical which decreased skeletal-related
events, palliated pain, and showed improved overall survival in symptomatic
patients with castration-resistant prostate cancer and bone metastasis only.
MATERIALS AND METHODS: We present the case of an eighty-two year old man with
metastatic castration-resistant prostate cancer who was treated with sequential
therapy (abiraterone - enzalutamide - radium 223). The sequencing and treatment
used for our patient was viable because of his clinical characteristics, which
have allowed for longer survival time with an acceptable quality of life. These
actions must be agreed on by the Multidisciplinary Tumour Board, in order to
optimize the use of available courses of treatment. RESULTS: The treatment of
these patients is changing rapidly, but many questions remain regarding the
optimal sequencing of the available drugs. Sequential or concomitant use of the
next generation hormonal agents - abiraterone and enzalutamide - cannot currently
be recommended. Data regarding the safety of concomitant abiraterone,
enzalutamide or denosumab with radium-223 is reassuring and timely. However, we
cannot advocate the general use of combined radium-223 therapy at this time,
irrespective of prior therapy. CONCLUSION: A better understanding of active
mechanisms, the genetic characteristics of each metastatic castration-resistant
prostate cancer and the development of new prognostic and predictive biomarkers
will help determine sequencing or different combination treatments for each
individual patient.
PMID- 29949529
TI - Gastric signet-ring cell carcinoma with hypersecretion of beta-Human chorionic
gonadotropin and review of the literature.
AB - beta-Human chorionic gonadotropin (beta-HCG) is an embryonic protein secreted by
the syncytiotrophoblast of the placenta. The determination of the plasma beta-HCG
level is routinely used for the diagnosis and the follow-up of germ cell tumors.
Some adenocarcinomas have been described as being rarely associated with beta-HCG
hypersecretion. We report a case of gastric signet-ring cell carcinoma with beta
HCG hypersecretion and propose hypotheses to explain the pathogenesis of such
hypersecretion.
PMID- 29949530
TI - Differentiated thyroid carcinomas associated with chronic thyroiditis: biological
and clinical properties.
AB - AIM: To determine biological and clinical features of papillary and follicular
thyroid carcinomas associated or not associated with chronic thyroiditis.
MATERIALS AND METHODS: The study was conducted by retrospective analysis of
medical histories of 2,459 patients with thyroid cancer. Tumor size, its category
according to the TNM system, multi-focal properties of tumor growth, carcinoma
invasiveness, as well as disease stage, rates of relapses and metastasis, and
also cumulative survival rates were analyzed. RESULTS: The tumor size in patients
with papillary or follicular carcinoma associated with thyroiditis was smaller
compared to the patients without thyroiditis. In the first case, the invasion
frequency into extrathyroid structure and into the capsule was also lower. Multi
focal growth of both carcinoma types was registered more frequently in the
presence of thyroiditis. The frequency of papillary carcinoma metastasis to
lateral cervical lymph nodes was lower in the presence of thyroiditis, the
frequency being equal for metastasis into lymph nodes of the VI lymph outflow
zone in both groups of patients (with and without thyroiditis). In the presence
of thyroiditis, the frequency of distant papillary carcinoma metastasis was
decreased, no metastases were detected in patients with follicular carcinoma. In
the group of patients with papillary carcinoma there was found no relation
between the presence of thyroiditis and disease stage, relapse rates, and
mortality levels; however, the risk of follicular carcinoma relapse was
significantly lower in patients with thyroiditis. CONCLUSIONS: The presence of
chronic thyroiditis in papillary carcinoma patients showed a certain positive
impact on the course of the disease, in particular, primary tumor growth,
invasion, and metastasis. Such effect is even more expressed in the patients with
follicular thyroid carcinoma.
PMID- 29949531
TI - Clinical and immunohistochemical features of primary breast cancer and
metachronous ovarian and endometrial tumors.
AB - : The aim of the study was to assess the patterns of development of metachronous
cancer (endometrial cancer, EC, and ovarian cancer, OC) in breast cancer (BC)
patients dependent of receptor phenotype of breast tumors. MATERIALS AND METHODS:
In the study, 63 patients with VS, who developed metachronous EC (n = 47) or OC
(n = 16) were enrolled. Expression of estrogen receptor (ER), progesterone
receptor (PR), HER/2neu was assessed using immunohistochemical approach. RESULTS:
BC in patients with metachronous EC and OC was characterized by a different
frequency of molecular subtypes with the dominance of luminal A (36%) and B (43%)
subtypes. In primary BC, we have established a correlation between ER expression
and regional lymph nodes status (r = -0.50, p < 0.05); negative correlation
between HER2/neu expression and tumor stage (r = -0.48, p < 0.05); between the
molecular subtype of BC and its size (r = -0.33, p <0.05), the molecular subtype
of primary BC and metastases in regional lymph nodes (r = 0.27, p <0.05). In the
patients with luminal subtype BC metachronous tumors developed with the highest
frequency (OC - 50%, EC - 50%). After treatment of primary BC metachronous tumors
developed at different period: EC (22.2%) - most often in 3-5 years, OC (11.0%) -
after 10 years and more. CONCLUSION: Our data evidence on the clinical
significance of the individual characteristics of the BC, especially its
molecular subtype, and the need to calculate the personalized risk of development
of metachronous tumors of the reproductive system in patients with the BC.
PMID- 29949532
TI - Anagrelide and the CALR mutation allele burden in essential thrombocythemia.
PMID- 29949533
TI - Lymphocyte count in peripheral blood is a sensitive tool in pretreatment
assessment of patients with urological cancer.
AB - : Cancer, inflammation and immune surveillance recruit lymphocytes as common key
cellular players. The aim of the study was to assess a utility of the absolute
and relative lymphocyte counts (ALC and RLC) in peripheral blood of patients with
urological cancer as sensitive tool in pretreatment assessment of patient, which
correlates with postoperative outcome of the disease, and outlines the overall
reactivity of the patient. MATERIALS AND METHODS: We retrospectively studied
correlation between lymphocyte count in peripheral blood of the patients with
urological cancer (n = 789) and number of clinical parameters: cancer
localization, stage of the disease, treatment outcome, complications. Mann -
Whitney two-tailed test and logistic regression models were used. RESULTS:
Lymphocyte counts (both absolute and relative) correlate with the cancer stage,
and status of the disease, allowing differentiate patients with urological
cancer, from healthy individuals, and from the cancer patients after radical
surgery. In patients with kidney and bladder cancer, lymphocyte count allowed
differentiate the stages of the disease. Lower rate of the reactivity of the
patient to the cancer treatment is accurately predicted by the ALC and RLC: those
in highest quartile for lymphocytes count have shorter postoperative recovery.
Patients in lowest quartile demonstrated worst postoperative performance,
including cases of early postoperative mortality due to weak somatic status.
CONCLUSION: The study presents evidence that pretreatment lymphocyte count in the
peripheral blood of patients with urological cancer is a sensitive marker of
cancer stage, and the reactivity of the patient to the cancer treatment, which
can be used in the pretreatment assessment of the patient.
PMID- 29949534
TI - Increased homocysteine plasma levels in breast cancer patients of a Mexican
population.
AB - AIM: Hyperhomocysteinemia has been associated with different pathologies,
including cardiovascular diseases, hypertension, diabetes, and breast cancer
(BC). To examine the differences in total homocysteine (tHcy) plasma levels, we
compared healthy women to BC patients from a Mexican population. MATERIALS AND
METHODS: The tHcy plasma levels were measured using high-performance liquid
chromatography with a fluorescence detector in 89 female controls and 261 BC
patients. RESULTS: The observed plasma tHcy levels were significantly higher
among the BC patients (11.1019 +/- 5.9161 umol/l) compared to the controls
(9.1046 +/- 1.3213 umol/l) (p = 0.002), and these differences were evident when
stratified by age (>= 50 years old), menopause status, overweight and obesity,
miscarriages, node metastases, progression, subtype classification (luminal, Her2
and triple negative) and nonresponse to chemotherapy. CONCLUSIONS: The tHcy
plasma levels could be a good marker for the progression and chemosensitivity of
BC in the analyzed sample from a Mexican population.
PMID- 29949536
TI - Materials of symposium and summer school "Fundamental Principles of Cancer
Biotherapy", May 21-23, 2018, Kyiv, Ukraine.
PMID- 29949535
TI - The analysis of methylation of DNA promoter of SFRP2 gene in patients with
hyperplastic processes of the endometrium.
AB - : The hyperplastic processes of the endometrium can arise not only against the
background of excessive influence of estrogen, but also against the background of
epigenetic damages that affect apoptosis, cell proliferation, differentiation,
and adhesion, and DNA reparation. The aim of our study was to investigate and
analyze the status of methylation of the promoter of SFRP2 gene in patients with
hyperplastic processes of the endometrium. MATERIALS AND METHODS: The study
groups were the following: I - patients with endometrial hyperplasia (EH, n = 9);
II - patients with endometrial intraepithelial neoplasia (EIN, n = 10), III -
control groups: 1) with endometrial cancer (EC, n = 4), and 2) healthy women (n =
4). Determination of promoter methylation of SFRP2 gene was carried out by the
semiquantitative method of methylation-specific PCR assay. RESULTS: The maximum
level of methylation of SFRP2 gene promoter had been revealed in patients with EC
- 42.80 +/- 3.55% (r < 0.05). The patients of the I group had the lowest values
of methylation of SFRP2 gene promoter - 10.66 +/- 0.85%, while in patients of the
II group this indicator was higher - 20.60 +/- 0.95% (r < 0.05). In healthy women
of the control group, methylation of SFRP2 gene promoter was detected in none of
the samples. CONCLUSION: The content of the methylated SFRP2 gene in endometrial
tissue of patients with hyperplastic processes higher than 20-25% allows relate
these women to the risk group of EC development and dictates the need of
intensive observation of such patients.
PMID- 29949537
TI - Expression of steroid and peptide hormone receptors, metabolic enzymes and EMT
related genes in prostate tumors in relation to the presence of the TMPRSS2/ERG
fusion.
AB - AIM: To analyze an expression pattern of the steroid and peptide hormone
receptors, metabolic enzymes and EMT-related genes in prostate tumors in relation
to the presence of the TMPRSS2/ERG fusion; and to examine a putative correlation
between gene expression and clinical characteristics, to define the molecular
subtypes of prostate cancer. MATERIALS AND METHODS: The relative gene expression
(RE) of 33 transcripts (27 genes) and the presence/absence of the TMPRSS2/ERG
fusion were analyzed by a quantitative PCR. 37 prostate cancer tissues (T) paired
with conventionally normal prostate tissue (CNT) and 21 samples of prostate
adenomas were investigated. RE changes were calculated, using different protocols
of statistics. RESULTS: We demonstrated differences in RE of seven genes between
tumors and CNT, as was calculated, using the 2-DeltaCT model and the Wilcoxon
matched paired test. Five genes (ESR1, KRT18, MKI67, MMP9, PCA3) showed altered
expression in adenocarcinomas, in which the TMPRSS2/ERG fusion was detected. Two
genes (INSR, isoform B and HOTAIR) expressed differently in tumors without
fusion. Comparison of the gene expression pattern in adenomas, CNT and
adenocarcinomas demonstrated that in adenocarcinomas, bearing the TMPRSS2/ERG
fusion, genes KRT18, PCA3, and SCHLAP1 expressed differently. At the same time,
we detected differences in RE of AR (isoform 2), MMP9, PRLR and HOTAIR in
adenocarcinomas without the TMPRSS2/ERG fusion. Two genes (ESR1 and SRD5A2)
showed differences in RE in both adenocarcinoma groups. Fourteen genes, namely AR
(isoforms 1 and 2), CDH1, OCLN, NKX3-1, XIAP, GCR (ins AG), INSR (isoform A),
IGF1R, IGF1R tr, PRLR, PRL, VDR and SRD5A2 showed correlation between RE and
tumor stage. RE of four genes (CDH2, ESR2, VDR and SRD5A2) correlated with
differentiation status of tumors (Gleason score). Using the K-means clustering,
we could cluster adenocarcinomas in three groups, according to gene expression
profiles. A specific subtype of prostate tumors is characterized by the activated
ERG signaling, due to the presence of TMPRSS2/ERG fusion, and also by high levels
of the androgen receptor, prolactin, IGF, INSR and PCA3. CONCLUSIONS: We have
found the specific differences in expression of the steroid and peptide hormone
receptors, metabolic enzymes and EMT-related genes, depending on the pre
sence/absence of the TMPRSS2/ERG fusion in prostate adenocarcinomas, CNT and
adenomas. We showed three different gene expression profiles of prostate
adenocarcinomas. One of them is characteristic for adenocarcinomas with the
TMPRSS2/ERG fusion. Further experiments are needed to confirm these data in a
larger cohort of patients.
PMID- 29949538
TI - Effect of valproic acid in comparison with vorinostat on cell growth inhibition
and apoptosis induction in the human colon cancer SW48 cells in vitro.
AB - AIM: Acetylation levels of histones are the result of the balance between histone
acetyltransfrases and histone deacetylases activities, which plays an important
role in chromatin remodeling and regulation of gene expression. Histone
deacetylases inhibitors such as valproic acid, vorinostat have attracted interest
because of their ability to induce differentiation and apoptosis of cancer cells.
The current study was designed to assess the effect of valproic acid in
comparison to and in combination with vorinostat on cell growth inhibition and
apoptosis induction in the human colon cancer SW48 cells. MATERIALS AND METHODS:
The colon cancer SW48 cells were seeded and treated with various doses of
valproic acid and vorinostat and MTT assay and flow cytometric assay were done to
determine cell viability and cell apoptosis, respectively. RESULTS: All
concentrations of both agents reduced viability significantly in a dose- and time
dependent fashion (p < 0.004). Both compounds, either single or combined agents,
induced apoptosis significantly, whereas the ratio of the apoptotic cells treated
with combined agents was more significant than the single. CONCLUSION: Our
findings suggest that vaproic acid and vorinostat can significantly inhibit cell
growth and induce apoptosis in colon cancer SW48 cells.
PMID- 29949540
TI - The Secret Life of the Sun.
PMID- 29949539
TI - Down regulation of u-PA by a nutrient mixture in hemangioma (EOMA) cells by
inducing caspase-dependent apoptosis.
AB - : Hemangiomas are the most common congenital vascular and benign tumor in infants
and children. Most hemangiomas do not cause major symptoms to require
intervention, however, the larger hemangiomas have tendency to bleed and may
require surgical removal. Experimental studies have demonstrated the role of
urokinase plasminogen activator (u-PA), especially cell surface u-PA, as an
initiator of extra-cellular matrix proteolysis and associated tumor cell
invasion. AIM: To examine, whether the antitumor effects of a specific nutrient
mixture are due to induction of apoptosis by inhibition of u-PA. MATERIALS AND
METHODS: A nutrient mixture containing lysine, proline, ascorbic acid, and green
tea extract which has showed anticancer activity against a number of cancer cell
lines was used as an experimental composition. EOMA cells were grown in
appropriate media with antibiotics in 24-well tissue culture plates. At near
confluence, the cells were treated with nutrition mixture at 10, 100, 1000 ug/ml
in triplicate. Analysis of u-PA activity was carried out by fibrin zymography.
Morphological changes and caspase activation associated with apoptosis induction
was checked by H&E staining and Live Green caspase assay, respectively. Apoptosis
inducing anticancer drug camptothecin (10 uM) was used as positive control.
RESULTS: The nutrition mixture exhibited dose response toxicity with maximum
toxicity 55% (p < 0.001) at 1000 ug/ml. EOMA cells expressed u-PA, which was
inhibited by nutrition mixture in a dose-dependent manner. The caspase analysis
revealed a dose dependent increase in apoptosis of EOMA hemangioma cells, with an
increasing apoptosis observed at 100 MUg/ml, and maximum at 1000 MUg/ml. Cells
treated with nutrition mixture showed significantly more apoptotic changes than
the control or camptothecin-treated cells. CONCLUSION: These results suggest that
NM may induce apoptosis of hemangioma cells in vitro thus warranting further
investigation.
PMID- 29949541
TI - Suffocated Seas.
PMID- 29949542
TI - Can You Supercharge Your Baby?
PMID- 29949543
TI - Looking at the Stars.
PMID- 29949544
TI - A Painful Mystery.
PMID- 29949546
TI - Quick Hits.
PMID- 29949545
TI - Apps We Really Need.
PMID- 29949547
TI - How Did Life Begin?
PMID- 29949548
TI - Bilingual Boost.
PMID- 29949549
TI - Milky Way Remapped.
PMID- 29949550
TI - This Book Stinks.
PMID- 29949551
TI - Knowledge Can Be Power.
PMID- 29949552
TI - Why We Won't Miss Opioids.
PMID- 29949554
TI - Who Owns the Dead?
PMID- 29949553
TI - What Is Spacetime?
PMID- 29949555
TI - Frozen Fungi.
PMID- 29949556
TI - How Much Can We Know?
PMID- 29949557
TI - 50, 100 &150 Years Ago.
PMID- 29949558
TI - Shrinking Animals.
PMID- 29949559
TI - What Is Consciousness?
PMID- 29949560
TI - Quirky Graphene.
PMID- 29949563
TI - What Are the Limits of Manipulating Nature?
PMID- 29949562
TI - Deathly Scent.
PMID- 29949561
TI - The Sun, Supercharging and the Search.
PMID- 29949564
TI - Letters.
PMID- 29949565
TI - A Good Life for All.
PMID- 29949566
TI - Into the Wildfire.
PMID- 29949567
TI - Soul-Searching.
PMID- 29949568
TI - What Is Dark Matter?
PMID- 29949570
TI - Recommended.
PMID- 29949569
TI - Couch Potato Persona.
PMID- 29949571
TI - Condensin ATPase motifs contribute differentially to the maintenance of
chromosome morphology and genome stability.
AB - Effective transfer of genetic information during cell division requires a major
reorganization of chromosome structure. This process is triggered by condensin, a
conserved pentameric ATPase essential for chromosome condensation. How condensin
harnesses the energy of ATP hydrolysis to promote chromatin reorganization is
unknown. To address this issue, we performed a genetic screen specifically
focused on the ATPase domain of Smc4, a core subunit of condensin. Our screen
identified mutational hotspots that impair condensin's ability to condense
chromosomes to various degrees. These mutations have distinct effects on
viability, genome stability, and chromosome morphology, revealing unique
thresholds for condensin enzymatic activity in the execution of its cellular
functions. Biochemical analyses indicate that inactivation of Smc4 ATPase
activity can result in cell lethality because it favors a specific configuration
of condensin that locks ATP in the enzyme. Together, our results provide critical
insights into the mechanism used by condensin to harness the energy of ATP
hydrolysis for the compaction of chromatin.
PMID- 29949572
TI - Meteorological factors and risk of hemorrhagic fever with renal syndrome in
Guangzhou, southern China, 2006-2015.
AB - BACKGROUND: The epidemic tendency of hemorrhagic fever with renal syndrome (HFRS)
is on the rise in recent years in Guangzhou. This study aimed to explore the
associations between meteorological factors and HFRS epidemic risk in Guangzhou
for the period from 2006-2015. METHODS: We obtained data of HFRS cases in
Guangzhou from the National Notifiable Disease Report System (NNDRS) during the
period of 2006-2015. Meteorological data were obtained from the Guangzhou
Meteorological Bureau. A negative binomial multivariable regression was used to
explore the relationship between meteorological variables and HFRS. RESULTS: The
annual average incidence was 0.92 per 100000, with the annual incidence ranging
from 0.64/100000 in 2009 to 1.05/100000 in 2012. The monthly number of HFRS cases
decreased by 5.543% (95%CI -5.564% to -5.523%) each time the temperature was
increased by 1 degrees C and the number of cases decreased by 0.075% (95%CI
0.076% to -0.074%) each time the aggregate rainfall was increased by 1 mm. We
found that average temperature with a one-month lag was significantly associated
with HFRS transmission. CONCLUSIONS: Meteorological factors had significant
association with occurrence of HFRS in Guangzhou, Southern China. This study
provides preliminary information for further studies on epidemiological
prediction of HFRS and for developing an early warning system.
PMID- 29949573
TI - Intracellular attenuation of BMP signaling via CKIP-1/Smurf1 is essential during
neural crest induction.
AB - The neural crest is induced at the neural plate border during gastrulation by
combined bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and
Wnt signaling. While intermediate BMP levels are critical for this induction,
secreted BMP inhibitors are largely absent from the neural plate border. Here, we
propose a morphogen model in which intracellular attenuation of BMP signaling
sets the required intermediate levels to maintain neural crest induction. We show
that the scaffold protein casein kinase interacting protein 1 (CKIP-1) and
ubiquitin ligase Smad ubiquitin regulatory factor 1 (Smurf1) are coexpressed with
BMP4 at the chick neural plate border. Knockdown of CKIP-1 during a critical
period between gastrulation and neurulation causes neural crest loss. Consistent
with specific BMP modulation, CKIP-1 loss suppresses phospho-Smads 1/5/8
(pSmad1/5/8) and BMP reporter output but has no effect on Wnt signaling; Smurf1
overexpression (OE) acts similarly. Epistasis experiments further show that CKIP
1 rescues Smurf1-mediated neural crest loss. The results support a model in which
CKIP-1 suppresses Smurf1-mediated degradation of Smads, uncovering an
intracellular mechanism for attenuation of BMP signaling to the intermediate
levels required for maintenance of neural crest induction.
PMID- 29949576
TI - On the apparent decrease in Olympic sprinter reaction times.
AB - Reaction times of Olympic sprinters provide insights into the most rapid of human
response times. To determine whether minimum reaction times have changed as
athlete training has become ever more specialized, we analyzed the results from
the Olympic Games between 2004 and 2016. The results for the 100 m and 110 m
hurdle events show that minimum reaction times have systematically decreased
between 2004 and 2016 for both sexes, with women showing a marked decrease since
2008 that eliminated the sex difference in 2012. Because overall race times have
not systematically decreased between 2004 and 2016, the most likely explanation
for the apparent decrease in reaction times is a reduction in the proprietary
force thresholds used to calculate the reaction times based on force sensors in
starting blocks-and not the result of more specialized or effective training.
PMID- 29949575
TI - Thalamocortical and intracortical laminar connectivity determines sleep spindle
properties.
AB - Sleep spindles are brief oscillatory events during non-rapid eye movement (NREM)
sleep. Spindle density and synchronization properties are different in MEG versus
EEG recordings in humans and also vary with learning performance, suggesting
spindle involvement in memory consolidation. Here, using computational models, we
identified network mechanisms that may explain differences in spindle properties
across cortical structures. First, we report that differences in spindle
occurrence between MEG and EEG data may arise from the contrasting properties of
the core and matrix thalamocortical systems. The matrix system, projecting
superficially, has wider thalamocortical fanout compared to the core system,
which projects to middle layers, and requires the recruitment of a larger
population of neurons to initiate a spindle. This property was sufficient to
explain lower spindle density and higher spatial synchrony of spindles in the
superficial cortical layers, as observed in the EEG signal. In contrast, spindles
in the core system occurred more frequently but less synchronously, as observed
in the MEG recordings. Furthermore, consistent with human recordings, in the
model, spindles occurred independently in the core system but the matrix system
spindles commonly co-occurred with core spindles. We also found that the
intracortical excitatory connections from layer III/IV to layer V promote spindle
propagation from the core to the matrix system, leading to widespread spindle
activity. Our study predicts that plasticity of intra- and inter-cortical
connectivity can potentially be a mechanism for increased spindle density as has
been observed during learning.
PMID- 29949577
TI - The cup fungus Pestalopezia brunneopruinosa is Pestalotiopsis gibbosa and belongs
to Sordariomycetes.
AB - Pestalopezia brunneopruinosa, the type species of Pestalopezia in Leotiomycetes,
produces typical cup-shaped ascomata. Because its asexual morph has conidia
comprised of five cells including apical and basal appendages and three pigmented
median cells, it was first described as Pestalotia gibbosa, which belongs to
Sordariomycetes. This contradiction has not been resolved due to the difficulty
in isolating this fungus in culture. In this study, we isolated separate strains
from the sexual morph and the asexual morph for molecular analysis. Phylogenetic
trees of Sporocadaceae based on internal transcribed spacer, partial beta
tubulin, and partial translation elongation factor 1-alpha sequence datasets
revealed that both strains fall into the same taxon, in a clade in Pestalotiopsis
sensu stricto alongside P. gaultheriae and P. spathulata. We provide the first
evidence that fungi producing cup-shaped ascomata in Pestalotiopsis belong to
Sordariomycetes, and we have proposed the transfer of Pestalopezia
brunneopruinosa to Pestalotiopsis gibbosa.
PMID- 29949574
TI - Evidence for plant-derived xenomiRs based on a large-scale analysis of public
small RNA sequencing data from human samples.
AB - In recent years, an increasing number of studies have reported the presence of
plant miRNAs in human samples, which resulted in a hypothesis asserting the
existence of plant-derived exogenous microRNA (xenomiR). However, this hypothesis
is not widely accepted in the scientific community due to possible sample
contamination and the small sample size with lack of rigorous statistical
analysis. This study provides a systematic statistical test that can validate (or
invalidate) the plant-derived xenomiR hypothesis by analyzing 388 small RNA
sequencing data from human samples in 11 types of body fluids/tissues. A total of
166 types of plant miRNAs were found in at least one human sample, of which 14
plant miRNAs represented more than 80% of the total plant miRNAs abundance in
human samples. Plant miRNA profiles were characterized to be tissue-specific in
different human samples. Meanwhile, the plant miRNAs identified from microbiome
have an insignificant abundance compared to those from humans, while plant miRNA
profiles in human samples were significantly different from those in plants,
suggesting that sample contamination is an unlikely reason for all the plant
miRNAs detected in human samples. This study also provides a set of testable
synthetic miRNAs with isotopes that can be detected in situ after being fed to
animals.
PMID- 29949578
TI - Changes in markers for cardio-metabolic disease risk after only 1-2 weeks of a
high saturated fat diet in overweight adults.
AB - PURPOSE: Diets high in saturated fat acids (SFA) have been linked with cardio
metabolic disease risk. The purpose of this study was to determine whether only 1
2 weeks of a high SFA diet could impact disease risk factors in overweight adults
who normally eat a relatively low proportion of SFA (i.e., <40% of dietary fat).
METHODS: Twelve overweight (BMI: 27+/-1 kg/m2) young adults were studied before
and after a 2-week diet that increased the proportion of SFA (<40% to 60% of
dietary fat), while maintaining their daily intake of total fat, carbohydrate,
protein, and calories. Insulin resistance, blood pressure, plasma markers of
liver damage, total plasma cholesterol concentrations, and fatty acid profile
within plasma and skeletal muscle lipid pools were assessed before and after the
intervention. RESULTS: Total plasma cholesterol concentration increased (148+/-5
vs. 164+/-8 mg/dl; P<0.05) after only one week, due exclusively to an increase in
LDL-cholesterol (78+/-4 vs. 95+/-7 mg/dl; P<0.05). After two weeks, plasma
aspartate amino transferase (AST) concentration increased (P<0.05) but we found
no change in insulin resistance, or resting blood pressure. The diet increase the
proportion of SFA in plasma (35+/-1% vs. 39+/-2%; P<0.05) and the
intramyocellular triglyceride pool (32+/-1% vs. 37+/-1%; P<0.05) suggesting the
fatty acids in these pools may readily exchange. CONCLUSIONS: Although blood
lipids remain within normal clinical range, increasing saturated fat in diet for
only 2 weeks raises plasma markers of cardiovascular risk (LDL-cholesterol) and
liver damage (AST). In overweight, but healthy-young adults SFA accumulate in
plasma and muscle after only 1-2 weeks of dietary increase.
PMID- 29949579
TI - Health literacy and use of preventive health services among North Korean
defectors in the Republic of Korea.
AB - It is known that some groups of immigrants can have low health literacy and it
may affect their health. Although the number of North Korean defectors in the
Republic of Korea has increased, little is known about their health literacy and
health behavior. Adult North Korean defectors (n = 399) in this study were
surveyed on health literacy, using the Korean Health Literacy Scale, and on the
use of preventive services. Those with better health literacy scores were more
likely to have vaccination than the lower scoring group (adjusted OR = 2.44; 95%
CI, 1.19-5.00). However, undergoing medical check-up may not be associated with
health literacy. In subgroup analysis, among defectors who lived alone (P =
0.032) or who had longer time in other countries before entering (P = 0.007), the
vaccination coverage was associated with their health literacy scores. This study
provides evidence for an association between health literacy and influenza
vaccination coverage among North Korean defectors even though they may have fewer
language barriers than other immigrants. Further research is needed to develop
interventions for improving health literacy and their preventive health behavior.
PMID- 29949580
TI - Multi locus sequence typing of Burkholderia pseudomallei isolates from India
unveils molecular diversity and confers regional association in Southeast Asia.
AB - OBJECTIVES: Burkholderia pseudomallei, the causative agent for melioidosis, has
become a public health problem in India and across the world. Melioidosis can be
difficult to diagnose because of the inconsistent clinical presentations of the
disease. This study aims to determine the genetic diversity among the clinical
isolates of B. pseudomaelli from India in order to establish a molecular
epidemiology and elucidate the Southeast Asian association. METHODS: Molecular
typing using multi locus sequence typing was performed on thirty one archived B.
pseudomallei clinical isolates, previously characterised from specimens obtained
from patients admitted to the Christian Medical College & Hospital, Vellore from
2015 to 2016. Further investigations into the genetic heterogeneity and evolution
at a regional and global level were performed using insilico tools. RESULTS:
Multi locus sequence typing (MLST) of the isolates from systemic and localized
forms of melioidosis, including blood, pus, tissue, and urine specimens, revealed
twenty isolates with novel sequence types and eleven with previously reported
sequence types. High genetic diversity was observed using MLST with a strong
association within the Southeast Asian region. CONCLUSIONS: Molecular typing of
B. pseudomallei clinical isolates using MLST revealed high genetic diversity and
provided a baseline molecular epidemiology of the disease in India with a strong
Southeast Asian association of the strains. Future studies should focus on whole
genome based Single-Nucleotide-Polymorphism (SNP) which has the advantage of a
high discriminatory power, to further understand the novel sequence types
reported in this study.
PMID- 29949581
TI - Analyses of phenotypic differentiations among South Georgian Diving Petrel
(Pelecanoides georgicus) populations reveal an undescribed and highly endangered
species from New Zealand.
AB - Unresolved taxonomy of threatened species is problematic for conservation as the
field relies on species being distinct taxonomic units. Differences in breeding
habitat and results from a preliminary molecular analysis indicated that the New
Zealand population of the South Georgian Diving Petrel (Pelecanoides georgicus)
was a distinct, yet undescribed, species. We measured 11 biometric characters and
scored eight plumage characters in 143 live birds and 64 study skins originating
from most populations of P. georgicus, to assess their taxonomic relationships.
We analysed differences with principal component analyses (PCA), factorial
ANOVAs, and Kruskal-Wallis rank sum tests. Results show that individuals from New
Zealand differ significantly from P. georgicus from all other populations as
following: 1) longer wings, 2) longer outer tail feathers, 3) deeper bills, 4)
longer heads, 5) longer tarsi, 6) limited collar extent, 7) greater extent of
contrasting scapulars, 8) larger contrasting markings on the secondaries, 9)
paler ear coverts, 10) paler collars, and 11) paler flanks. Furthermore, we used
a species delimitation test with quantitative phenotypic criteria; results reveal
that the New Zealand population of P. georgicus indeed merits species status. We
hereby name this new species Pelecanoides whenuahouensis sp. nov. Due to severe
reductions in its range and the very low number of remaining birds (~150
individuals limited to a single breeding colony on Codfish Island/Whenua Hou) the
species warrants listing as 'Critically Endangered'. An abstract in the Maori
language/Te Reo Maori can be found in S1 File.
PMID- 29949583
TI - A Web Geographic Information System to share data and explorative analysis tools:
The application to West Nile disease in the Mediterranean basin.
AB - BACKGROUND: In the last decades an increasing number of West Nile Disease cases
was observed in equines and humans in the Mediterranean basin and surveillance
systems are set up in numerous countries to manage and control the disease. The
collection, storage and distribution of information on the spread of the disease
becomes important for a shared intervention and control strategy. To this end, a
Web Geographic Information System has been developed and disease data, climatic
and environmental remote sensed data, full genome sequences of selected isolated
strains are made available. This paper describes the Disease Monitoring Dashboard
(DMD) web system application, the tools available for the preliminary analysis on
climatic and environmental factors and the other interactive tools for
epidemiological analysis. METHODS: WNV occurrence data are collected from
multiple official and unofficial sources. Whole genome sequences and metadata of
WNV strains are retrieved from public databases or generated in the framework of
the Italian surveillance activities. Climatic and environmental data are provided
by NASA website. The Geographical Information System is composed by Oracle 10g
Database and ESRI ArcGIS Server 10.03; the web mapping client application is
developed with the ArcGIS API for Javascript and Phylocanvas library to
facilitate and optimize the mash-up approach. ESRI ArcSDE 10.1 has been used to
store spatial data. RESULTS: The DMD application is accessible through a generic
web browser at https://netmed.izs.it/networkMediterraneo/. The system collects
data through on-line forms and automated procedures and visualizes data as
interactive graphs, maps and tables. The spatial and temporal dynamic
visualization of disease events is managed by a time slider that returns results
on both map and epidemiological curve. Climatic and environmental data can be
associated to cases through python procedures and downloaded as Excel files.
CONCLUSIONS: The system compiles multiple datasets through user-friendly web
tools; it integrates entomological, veterinary and human surveillance, molecular
information on pathogens and environmental and climatic data. The principal
result of the DMD development is the transfer and dissemination of knowledge and
technologies to develop strategies for integrated prevention and control measures
of animal and human diseases.
PMID- 29949582
TI - A murine glaucoma model induced by rapid in vivo photopolymerization of
hyaluronic acid glycidyl methacrylate.
AB - Glaucoma is an optic neuropathy commonly associated with elevated intraocular
pressure (IOP) resulting in progressive loss of retinal ganglion cells (RGCs) and
optic nerve degeneration, leading to blindness. New therapeutic approaches that
better preserve the visual field by promoting survival and health of RGCs are
highly needed since RGC death occurs despite good IOP control in glaucoma
patients. We have developed a novel approach to reliably induce chronic IOP
elevation in mouse using a photopolymerizable biomatrix, hyaluronic acid glycidyl
methacrylate. This is achieved by rapid in vivo crosslinking of the biomatrix at
the iridocorneal angle by a flash of ultraviolet A (UVA) light to impede the
aqueous outflow pathway with a controllable manner. Sustained IOP elevation was
induced after a single manipulation and was maintained at ~45% above baseline for
>4 weeks. Significant thinning of the inner retina and ~35% reduction in RGCs and
axons was noted within one month of IOP elevation. Optic nerve degeneration
showed positive correlation with cumulative IOP elevation. Activation of
astrocytes and microglia appeared to be an early event in response to IOP
elevation preceding detectable RGC and axon loss. Attenuated glial reactivity was
noted at later stage where significant RGC/axon loss had occurred suggesting
astrocytes and microglia may play different roles over the course of glaucomatous
degeneration. This novel murine glaucoma model is reproducible and displays
cellular changes that recapitulate several pathophysiological features of
glaucoma.
PMID- 29949584
TI - High rebound mattress toppers facilitate core body temperature drop and enhance
deep sleep in the initial phase of nocturnal sleep.
AB - Recently, several new materials for mattresses have been introduced. Although
some of these, such as low rebound (pressure-absorbing/memory foam) and high
rebound mattresses have fairly different characteristics, effects of these
mattresses on sleep have never been scientifically evaluated. In the current
study, we have evaluated effects of a high rebound mattress topper [HR] on sleep
and its associated physiology, and the effects were compared to those of a low
rebound mattress toppers (LR) in healthy young (n = 10) and old (n = 20) adult
males with a randomized, single-blind, cross over design. We found that sleeping
with HR compared to LR induced a larger decline in core body temperature (CBT) in
the initial phase of nocturnal sleep both in young (minimum CBT: 36.05 vs 36.35
degrees C) and old (minimum CBT: 36.47 vs. 36.55 degrees C) subjects, and
declines in the CBT were associated with increases in deep sleep/delta power
(+27.8% in young and +24.7% in old subjects between 11:00-01:00). We also found
significantly smaller muscle activities during roll over motions with HR (-53.0
to -66.1%, depending on the muscle) during a separate daytime testing. These
results suggest that sleeping with HR in comparison to with LR, may facilitate
restorative sleep at the initial phase of sleep.
PMID- 29949585
TI - Real or bogus: Predicting susceptibility to phishing with economic experiments.
AB - We present a lab-in-the-field experiment to demonstrate how individual behavior
in the lab predicts their ability to identify phishing attempts. Using the
business and finance staff members from a large public university in the U.S., we
find that participants who are intolerant of risk, more curious, and less
trusting commit significantly more errors when evaluating interfaces. We also
replicate prior results on demographic correlates of phishing vulnerability,
including age, gender, and education level. Our results suggest that behavioral
characteristics such as intolerance of risk, curiosity, and trust can be used to
predict individual ability to identify phishing interfaces.
PMID- 29949586
TI - A subset of octopaminergic neurons that promotes feeding initiation in Drosophila
melanogaster.
AB - Octopamine regulates feeding behavioral responses in Drosophila melanogaster,
however the molecular and circuit mechanisms have not been fully elucidated.
Here, we investigated the role of a subset of octopaminergic neurons, the OA-VPM4
cluster, in sucrose acceptance behavior. Thermogenetic activation of Gal4 lines
containing OA-VPM4 promoted proboscis extension to sucrose, while optogenetic
inactivation reduced extension. Anatomically, the presynaptic terminals of OA
VPM4 are in close proximity to the axons of sugar-responsive gustatory sensory
neurons. Moreover, RNAi knockdown of a specific class of octopamine receptor,
OAMB, selectively in sugar-sensing gustatory neurons decreased the behavioral
response to sucrose. By calcium imaging experiments, we found that application of
octopamine potentiates sensory responses to sucrose in satiated flies. Taken
together, these findings suggest a model by which OA-VPM4 promotes feeding
behavior by modulating the activity of sensory neurons.
PMID- 29949587
TI - Should kissing balloon inflation after main vessel stenting be routine in the one
stent approach? A systematic review and meta-analysis of randomized trials.
AB - The KBI (kissing balloon inflation) technique is considered the default strategy
for the two-stent approach in real world practice. Studies comparing KBI and No
KBI in patients undergoing the one-stent approach have reported conflicting
results. The meta-analysis was performed to compare the clinical outcomes of the
KBI strategy and the No-KBI strategy for coronary bifurcation lesions in the one
stent approach. Five randomized studies were included, and a total of 1264
patients were involved in the meta-analysis. The primary outcome was cardiac
death. The secondary end points were stent thrombosis, MI (myocardial
infarction), target lesion revascularization (TLR), target vessel
revascularization (TVR), and main vessel and side branch restenosis. Compared
with the No-KBI strategy, the KBI strategy was associated with a significant
reduction in side branch restenosis (OR: 0.44, 95% CI: 0.30-0.64, p<0.001). A
high risk of main vessel restenosis was found in the KBI group (OR: 2.96, 95% CI:
1.74-5.01, p<0.001). There were no significant differences in rates of cardiac
death (OR: 1.89, 95% CI: 0.60-5.95, p = 0.28), stent thrombosis (OR: 0.98, 95%
CI: 0.19-4.94, p = 0.98), MI (OR: 0.68, 95% CI: 0.33-1.44, p = 0.30), TLR (OR
1.14, 95% CI 0.68-1.90, p = 0.62), or TVR (OR 1.27, 95% CI 0.75-2.16, p = 0.38).
Compared with the No-KBI strategy, the KBI strategy reduced the incidence of side
branch restenosis and increased the risk of main branch restenosis in the one
stent approach. However, the clinical outcomes were similar between the KBI and
No-KBI groups.
PMID- 29949588
TI - Identifying priority conservation landscapes and actions for the Critically
Endangered Javan leopard in Indonesia: Conserving the last large carnivore in
Java Island.
AB - With the extirpation of tigers from the Indonesian island of Java in the 1980s,
the endemic and Critically Endangered Javan leopard is the island's last
remaining large carnivore. Yet despite this, it has received little conservation
attention and its population status and distribution remains poorly known. Using
Maxent modeling, we predicted the locations of suitable leopard landscapes
throughout the island of Java based on 228 verified Javan leopard samples and as
a function of seven environmental variables. The identified landscapes covered
over 1 million hectares, representing less than 9% of the island. Direct evidence
of Javan leopard was confirmed from 22 of the 29 identified landscapes and
included all national parks, which our analysis revealed as the single most
important land type. Our study also emphasized the importance of maintaining
connectivity between protected areas and human-modified landscapes because
adjacent production forests and secondary forests were found to provide vital
extensions for several Javan leopard subpopulations. Our predictive map greatly
improves those previously produced by the Government of Indonesia's Javan Leopard
Action Plan and the IUCN global leopard distribution assessment. It shares only a
32% overlap with the IUCN range predictions, adds six new priority landscapes,
all with confirmed presence of Javan leopard, and reveals an island-wide leopard
population that occurs in several highly fragmented landscapes, which are far
more isolated than previously thought. Our study provides reliable information on
where conservation efforts must be prioritized both inside and outside of the
protected area network to safeguard Java's last remaining large carnivore.
PMID- 29949590
TI - New 1,3-benzodioxin-4-ones from Synnemapestaloides ericacearum sp. nov., a
biosynthetic link to remarkable compounds within the Xylariales.
AB - Surveys of foliar endophytes from the Acadian forest region over the past three
decades have identified numerous phylogenetically diverse fungi producing natural
products toxic to forest pests and diseases. The life histories of some conifer
endophytes can be restricted to plant foliage or may include saprotrophic phases
on other plants tissues or even alternate hosts. Considering the potentially
broad host preferences of conifer endophytes we explored fungi isolated from
understory species and their metabolites as part of an ongoing investigation of
fungal biodiversity from the Acadian forest. We report a hitherto unidentified
Xylariomycetidae species isolated from symptomatic Labrador tea (Rhododendron
groenlandicum) leaves and mountain laurel (Kalmia latifolia) collected in coastal
southern New Brunswick, Canada. Morphological and phylogenetic evidence
demonstrated the unknown species was a novel Synnemapestaloides (Sporocadaceae)
species, described here as Syn. ericacearum. A preliminary screening assay
indicated that the culture filtrate extract of the new species was potently
antifungal towards the biotrophic pathogen Microbotryum violaceum, warranting an
investigation of its natural products. Two natural products possessing a rare 1,3
benzodioxin-4-one scaffold, synnemadoxins A-B (1-2), and their postulated
precursor, synnemadiacid A (3), were characterized as new structures and assessed
for antimicrobial activity. All isolated compounds elicited in vitro inhibitory
antifungal activity towards M. violaceum at 2.3 MUg mL-1 and moderate antibiotic
activity. Further, the characterization of synnemadoxins A-B provided a
perspective on the biosynthesis of some related 1,3-benzodioxin-4-ones produced
by other fungi within the Xylariales.
PMID- 29949589
TI - Association of functional and structural social support with medication adherence
among individuals treated for coronary heart disease risk factors: Findings from
the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
AB - BACKGROUND: Functional social support has a stronger association with medical
treatment adherence than structural social support in several populations and
disease conditions. Using a contemporary U.S. population of adults treated with
medications for coronary heart disease (CHD) risk factors, the association
between social support and medication adherence was examined. METHODS: We
included 17,113 black and white men and women with CHD or CHD risk factors aged
>=45 years recruited 2003-2007 from the REasons for Geographic and Racial
Differences in Stroke (REGARDS) study. Participants reported their perceived
social support (structural social support: being partnered, number of close
friends, number of close relatives, and number of other adults in household;
functional social support: having a caregiver in case of sickness or disability;
combination of structural and functional social support: number of close friends
or relatives seen at least monthly). Medication adherence was assessed using a 4
item scale. Multi-variable adjusted Poisson regression models were used to
calculate prevalence ratios (PR) for the association between social support and
medication adherence. RESULTS: Prevalence of medication adherence was 68.9%.
Participants who saw >10 close friends or relatives at least monthly had higher
prevalence of medication adherence (PR = 1.06; 95% CI: 1.00, 1.11) than those who
saw <=3 per month. Having a caregiver in case of sickness or disability, being
partnered, number of close friends, number of close relatives, and number of
other adults in household were not associated with medication adherence after
adjusting for covariates. CONCLUSIONS: Seeing multiple friends and relatives was
associated with better medication adherence among individuals with CHD risk
factors. Increasing social support with combined structural and functional
components may help support medication adherence.
PMID- 29949591
TI - Mechanical stress caused by wind on leaves of Theobroma cacao: Photosynthetic,
molecular, antioxidative and ultrastructural responses.
AB - Theobroma cacao is cultivated in the shade, in a so-called 'Cabruca' system, in
intercropped with Erithryna or other tree species of economic value, and in full
sun as a monoculture in irrigated or chemically-irrigated systems. Since it is a
species quite intolerant to wind, it is practically impossible to implant cacao
crops under full exposure to the sun, or in areas of frequent winds, without the
protection of windbreaks, using arboreal species around the area of culture in
the form of box. Wind can cause mechanical stimuli in plants, affecting their
growth and development. The objective of this work was to evaluate the
photosynthetic changes in mature leaves and the molecular, biochemical and
ultrastructural changes in young and mature leaves of the CCN 51 cloned genotype
of T. cacao subjected to intermittent (IW) and constant (CW) wind, with
velocities of 2.5, 3.5 and 4.5 m s-1, during 3, 6 and 12 h of exposure. It was
verified that CW and IW, considering different exposure times, interfered
directly in stomatal conductance (gs), transpiration (E) and water use efficiency
(WUE), causing a reduction of the photosynthetic rate (A) in mature leaves. In
addition, the pulvinus and blade of young and mature leaves, exposed to IW and CW
with different exposure times (3 and 12 h), showed marked macroscopic and
microscopic mechanical injuries resulting from the constant leaf movement. At
both speeds, there was rupture of the cell nuclear membrane in pulvinus and the
mesophyll tissues, mainly in the young leaves. On the other hand, in young and
mature leaves exposed to CW and IW at different speeds and exposure times, there
was lipid peroxidation, increased activity of guaiacol (GPX) and ascorbate (APX)
peroxidases in most treatments; and altered expression of transcripts of psba and
psbo genes related to the phothosynthetic apparatus and Cu-Zn-sod and per genes
related to antioxidative enzymes at the rate of 4.5 m s-1. Younger leaves were
more intolerant to mechanical stress caused by the wind, since presented greater
macro and microscopic damages and, consequently, greater molecular, biochemical
and ultrastructural changes. High wind speeds can seriously compromise the
development of young leaves of T. cacao plants and affect their productivity.
PMID- 29949592
TI - Cholera outbreak caused by drinking contaminated water from a lakeshore water
collection site, Kasese District, south-western Uganda, June-July 2015.
AB - On 20 June 2015, a cholera outbreak affecting more than 30 people was reported in
a fishing village, Katwe, in Kasese District, south-western Uganda. We
investigated this outbreak to identify the mode of transmission and to recommend
control measures. We defined a suspected case as onset of acute watery diarrhoea
between 1 June and 15 July 2015 in a resident of Katwe village; a confirmed case
was a suspected case with Vibrio cholerae cultured from stool. For case finding,
we reviewed medical records and actively searched for cases in the community. In
a case-control investigation we compared exposure histories of 32 suspected case
persons and 128 age-matched controls. We also conducted an environmental
assessment on how the exposures had occurred. We found 61 suspected cases (attack
rate = 4.9/1000) during this outbreak, of which eight were confirmed. The primary
case-person had onset on 16 June; afterwards cases sharply increased, peaked on
19 June, and rapidly declined afterwards. After 22 June, eight scattered cases
occurred. The case-control investigation showed that 97% (31/32) of cases and 62%
(79/128) of controls usually collected water from inside a water-collection site
"X" (ORM-H = 16; 95% CI = 2.4-107). The primary case-person who developed
symptoms while fishing, reportedly came ashore in the early morning hours on 17
June, and defecated "near" water-collection site X. We concluded that this
cholera outbreak was caused by drinking lake water collected from inside the
lakeshore water-collection site X. At our recommendations, the village
administration provided water chlorination tablets to the villagers, issued water
boiling advisory to the villagers, rigorously disinfected all patients' faeces
and, three weeks later, fixed the tap-water system.
PMID- 29949593
TI - Feasibility of using smartphones by village health workers for pregnancy
registration and effectiveness of mobile phone text messages on reduction of
homebirths in rural Uganda.
AB - INTRODUCTION: Homebirths are common in low and middle income countries and are
associated with poor child survival. We assessed the feasibility of using
smartphones by village health workers for pregnancy registration and the
effectiveness of health text messages (SMS) sent to pregnant women through
village health workers in reducing homebirths in rural Uganda. METHODS: A non
randomised intervention study was undertaken in 26 villages. In the intervention
arm, village health workers registered pregnant women (n = 262) in 13 villages
using a smartphone app (doForm) and paper forms and gestation age-timed SMS were
sent through village health workers to the pregnant women. In 13 control
villages, (n = 263) pregnant women were registered on paper forms only and no SMS
was sent. The main outcome was place of birth measured through a self-report.
Logistic regression with generalised estimating equations was used to explore the
effect of the intervention. RESULTS: Comparing 795 corresponding data fields on
phone and paper revealed that numeric variable fields were 86%-95% similar while
text fields were 38%-48% similar. Of the 525 pregnant women followed, 83 (15.8%)
delivered at home. In the adjusted analysis, the intervention was associated with
lower odds of homebirths [AOR = 0.38, 95%CI (0.15-0.97)]. Muslim religion [AOR =
4.0, 95%CI (1.72-9.34)], primary or no maternal education [AOR = 2.51, 95%CI
(1.00-6.35)] and health facility distance >= 2 km [AOR = 2.26, 95%CI (0.95-5.40)]
were independently associated with homebirths. CONCLUSION: Village health workers
can register pregnant women at home using phones and relay gestation age specific
SMS to them to effectively reduce homebirths.
PMID- 29949594
TI - Prevalence of HIV infection, access to HIV care, and response to antiretroviral
therapy among partners of HIV-infected individuals in Thailand.
AB - BACKGROUND: Health care providers usually focus on index HIV-infected patients
and seldom obtain information from their partners. We aimed to determine HIV
preventative measures among couples, the prevalence of HIV infection, and
treatment outcomes of partners. METHODS: This cross-sectional study was conducted
in two hospital settings, a university hospital in Bangkok and a general hospital
in northeastern Thailand, from January 2011-October 2015. Factors associated with
serodiscordant relationships were determined by logistic regression. RESULTS: A
total of 393 couples were enrolled for analysis; 156 (39.7%) were serodiscordant.
The median relationship duration of serodiscordant couples was shorter than that
of seroconcordant couples (6.4 years vs 11.6 years, p < 0.001). Of 237 HIV
infected partners, 17.7% had AIDS-defining illness, the median nadir CD4 count
(interquartile range) was 240 (96-427) cells/mm3, 83.5% received antiretroviral
therapy (ART), 98.3% had adherence > 95%, 90.3% had undetectable HIV RNA, and
22.9% had a prior history of treatment failure. There was no significant
difference in condom usage in the prior 30 days between serodiscordant and
seroconcordant couples. Factors of index HIV-infected patients associated with
serodiscordant relationships were younger age (odds ratio [OR] 1.04 per 5 years;
95% confidence interval [CI] 1.01-1.06), receiving care at the general hospital
(OR 1.73; 95% CI 1.08-2.78), a shorter duration of relationship (OR 1.04 per
year; 95% CI 1.01-1.07), a higher nadir CD4 count (OR 1.06 per 50 cells/mm3; 95%
CI 1.1-1.13), and not receiving a protease inhibitor-based regimen (OR 2.04; 95%
CI 1.06-3.96). CONCLUSIONS: A high number of serodiscordant couples was
determined. Partners' information should be retrieved as a holistic approach.
Interventions for minimizing HIV transmission within serodiscordant couples
should be evaluated and implemented.
PMID- 29949595
TI - Quality of flow diagram in systematic review and/or meta-analysis.
AB - Systematic reviews and/or meta-analyses generally provide the best evidence for
medical research. Authors are recommended to use flow diagrams to present the
review process, allowing for better understanding among readers. However, no
studies as of yet have assessed the quality of flow diagrams in systematic
review/meta-analyses. Our study aims to evaluate the quality of systematic
review/meta-analyses over a period of ten years, by assessing the quality of the
flow diagrams, and the correlation to the methodological quality. Two hundred
articles of "systematic review" and/or "meta-analysis" from January 2004 to
August 2015 were randomly retrieved in Pubmed to be assessed for the flow diagram
and methodological qualities. The flow diagrams were evaluated using a 16-grade
scale corresponding to the four stages of PRISMA flow diagram. It composes four
parts: Identification, Screening, Eligibility and Inclusion. Of the 200 articles
screened, 154 articles were included and were assessed with AMSTAR checklist.
Among them, 78 articles (50.6%) had the flow diagram. Over ten years, the
proportion of papers with flow diagram available had been increasing
significantly with regression coefficient beta = 5.649 (p = 0.002). However, the
improvement in quality of the flow diagram increased slightly but not
significantly (regression coefficient beta = 0.177, p = 0.133). Our analysis
showed high variation in the proportion of articles that reported flow diagram
components. The lowest proportions were 1% for reporting methods of duplicates
removal in screening phase, followed by 6% for manual search in identification
phase, 22% for number of studies for each specific/subgroup analysis, 27% for
number of articles retrieved from each database, and 31% for number of studies
included in qualitative analysis. The flow diagram quality was correlated with
the methodological quality with the Pearson's coefficient r = 0.32 (p = 0.0039).
Therefore, this review suggests that the reporting quality of flow diagram is
less satisfactory, hence not maximizing the potential benefit of the flow
diagrams. A guideline with standardized flow diagram is recommended to improve
the quality of systematic reviews, and to enable better reader comprehension of
the review process.
PMID- 29949596
TI - Overexpression of cytochrome P450s in a lambda-cyhalothrin resistant population
of Apolygus lucorum (Meyer-Dur).
AB - The mirid bug, Apolygus lucorum Meyer-Dur, has been an important pest of cotton
crop in China, and is primarily controlled with insecticides, such as
pyrethroids. To elucidate the potential resistant mechanisms of A. lucorum to
lambda-cyhalothrin, a series of biological, biochemical, and molecular assays
were conducted in the reference (AL-S) and lambda-cyhalothrin-resistant (AL-R)
populations. Comparison of the molecular target of pyrethroid insecticides,
voltage-gated sodium channel, revealed that there were no mutation sites in the
resistant population, indicating target insensitivity is not responsible for
increased resistance of AL-R to lambda-cyhalothrin. Furthermore, the synergism
assays and the activities of detoxification enzymes were performed to determine
detoxification mechanism conferring the lambda-cyhalothrin resistance. In the
tested synergists, the piperonyl butoxide had the highest synergism ratio against
lambda-cyhalothrin, which was up to five-fold in both populations. In addition,
the result also showed that only cytochrome P450 had significantly higher O
deethylase activity with 7-ethoxycoumarin (1.78-fold) in AL-R population compared
with AL-S population. Seven cytochrome P450 genes were found to be significantly
overexpressed in the resistant AL-R population compared with AL-S population.
Taken together, these results demonstrate that multiple over-transcribed
cytochrome P450 genes would be involved in the development of lambda-cyhalothrin
resistance in AL-R population.
PMID- 29949597
TI - Avian lungs: A novel scaffold for lung bioengineering.
AB - Allogeneic lung transplant is limited both by the shortage of available donor
lungs and by the lack of suitable long-term lung assist devices to bridge
patients to lung transplantation. Avian lungs have different structure and
mechanics resulting in more efficient gas exchange than mammalian lungs.
Decellularized avian lungs, recellularized with human lung cells, could therefore
provide a powerful novel gas exchange unit for potential use in pulmonary
therapeutics. To initially assess this in both small and large avian lung models,
chicken (Gallus gallus domesticus) and emu (Dromaius novaehollandiae) lungs were
decellularized using modifications of a detergent-based protocol, previously
utilized with mammalian lungs. Light and electron microscopy, vascular and airway
resistance, quantitation and gel analyses of residual DNA, and
immunohistochemical and mass spectrometric analyses of remaining extracellular
matrix (ECM) proteins demonstrated maintenance of lung structure, minimal
residual DNA, and retention of major ECM proteins in the decellularized
scaffolds. Seeding with human bronchial epithelial cells, human pulmonary
vascular endothelial cells, human mesenchymal stromal cells, and human lung
fibroblasts demonstrated initial cell attachment on decellularized avian lungs
and growth over a 7-day period. These initial studies demonstrate that
decellularized avian lungs may be a feasible approach for generating functional
lung tissue for clinical therapeutics.
PMID- 29949598
TI - Global patterns of crop yield stability under additional nutrient and water
inputs.
AB - Agricultural production must increase to feed a growing and wealthier population,
as well as to satisfy increasing demands for biomaterials and biomass-based
energy. At the same time, deforestation and land-use change need to be minimized
in order to preserve biodiversity and maintain carbon stores in vegetation and
soils. Consequently, agricultural land use needs to be intensified in order to
increase food production per unit area of land. Here we use simulations of
AgMIP's Global Gridded Crop Model Intercomparison (GGCMI) phase 1 to assess
implications of input-driven intensification (water, nutrients) on crop yield and
yield stability, which is an important aspect in food security. We find region-
and crop-specific responses for the simulated period 1980-2009 with broadly
increasing yield variability under additional nitrogen inputs and stabilizing
yields under additional water inputs (irrigation), reflecting current patterns of
water and nutrient limitation. The different models of the GGCMI ensemble show
similar response patterns, but model differences warrant further research on
management assumptions, such as variety selection and soil management, and inputs
as well as on model implementation of different soil and plant processes, such as
on heat stress, and parameters. Higher variability in crop productivity under
higher fertilizer input will require adequate buffer mechanisms in trade and
distribution/storage networks to avoid food price volatility.
PMID- 29949599
TI - Shale gas reservoir characterization: A typical case in the Southeast Chongqing
of Sichuan Basin, China.
AB - The Lower Silurian Longmaxi Shale in Southeast Chongqing of Sichuan Basin in
China is considered to be a potential shale gas reservoir by many scholars in
recent years. The special shale gas well, namely, Pengye-1 well, was selected as
a case study to evaluate the characteristics of the shale gas reservoir. A series
of experiments were performed to analyze the geochemical, mineralogical, and
petrophysical features and gas content using samples of the Longmaxi Shale from
Pengye-1 well. The results show that the organic and inorganic porosities of
these samples are range of 0.08-2.73% and 0.06-2.65%, with the average of 1.10%
and 1.76%, respectively. The inorganic pores primarily contribute to the porosity
until the TOC content is more than 3%. Organic matter plays an important role in
adsorbed gas content. The adsorbed gas is dominant in the Longmaxi Shale of
Pengye-1 well, which ranges from 0.46 to 2.24 cm3/g, with an average of 1.38
cm3/g. The free gas content ranges from 0.45 to 0.84 cm3/g with an average of
0.68 cm3/g, and is 24.4-49.7 percent of total gas with an average of 37.5%. The
bottom part of the Longmaxi Shale is the most favorable for shale gas exploring,
which is higher of brittleness mineral content, porosity and gas content. Compare
with the other five shales in America, the Lower Silurian Longmaxi Shale is
derived from older sedimentary periods with significantly higher thermal maturity
and has experienced several periods of intense tectonic, which are unfavorable
for the shale gas enrichment.
PMID- 29949600
TI - Associations between lean mass and leptin in men with chronic spinal cord injury:
Results from the FRASCI-muscle study.
AB - Leptin is an adipo-myokine that regulates appetite and energy expenditure by a
neuroendocrine feedback loop. Leptin levels are positively correlated with BMI in
the spinal cord injury population and leptin levels are greater in individuals
with spinal cord injury compared to uninjured controls. Leptin is produced in
multiple tissues, including fat, bone, and skeletal muscle and is a putative
biomarker of sedentary behavior in older adults. We assessed body composition
leptin, adiponectin, and IL-6 levels in 205 men with chronic spinal cord injury.
We found no association between age, injury duration, injury level, injury
completeness, or walking status and leptin. There was a significant positive
association between lean mass and leptin in men with SCI that was independent of
fat. Adjusting for body composition, leptin levels were positively associated
with IL-6 and negatively associated with adiponectin levels. When considering men
with SCI and sarcopenic obesity, only fat mass remained positively associated
with leptin. We found no association between IL-6, adiponectin, or lean mass and
leptin in the sarcopenic obesity group. Our findings suggest that lean mass is an
under recognized, but substantial, source of circulating leptin. Furthermore, SCI
related sarcopenic obesity may result in dysregulated adipo-myokine metabolism
with local and systemic physiologic effects.
PMID- 29949601
TI - Patterns of computer and Internet use and its association with HIV knowledge in
selected countries in sub-Saharan Africa.
AB - BACKGROUND: Healthcare systems in Sub-Saharan Africa (SSA) are fraught with
numerous governance and infrastructural issues including lack of access to
quality care and health worker shortage. Policy makers are becoming increasingly
interested in adopting novel technologies such as web-based interventions within
the scope of e-Health to bridge the gaps in care delivery in a cost-effective and
sustainable manner. Successful implementation of these policies is reliant on
evidences regarding people's access to these technologies, which are scarce for
countries in SSA. OBJECTIVES: To 1) investigate the variation in the prevalence
of accessing computer and internet across regional and socioeconomic groups, and
2) assess association between ever accessing computer and internet and knowledge
of routes and risk factors of HIV transmission in selected SSA countries.
METHODS: We analyzed cross-sectional datasets from UNICEF Multiple Indicator
Cluster Surveys. Participants were16,194 men and 39,121 women from Ghana, Guinea
Bissau, Malawi and Zimbabwe. Main outcome variable was ever-accessing computer
and Internet for any purpose. Associations were assessed by multivariable
regression methods. RESULTS: Lifetime computer usage in Ghana, Guinea Bissau,
Malawi and Zimbabwe was respectively 21.5%, 13.4%, 12.3%, 28.4% among men, and
12.5%, 8.3%, 4.8%, 20.5% among women, and that of internet was 14.9%, 11.7%,
10.8%, 34% among men, and 6.4%, 6.9%, 4.2%, 21.6% among women in the
aforementioned order. Participants who reported ever using computer and Internet
were more likely to have higher knowledge regarding the transmission of HIV
compared to those who did not. CONCLUSIONS: Prevalence of lifetime access to
computer and Internet was considerably low in all four countries. Several
socioeconomic factors appeared to be associated with the access to computer and
Internet, addressing which might prove beneficial for the successful expansion e
Health in these countries.
PMID- 29949602
TI - Novel pathway for mutagenic tautomerization of classical A?T DNA base pairs via
sequential proton transfer through quasi-orthogonal transition states: A QM/QTAIM
investigation.
AB - In this paper we have theoretically predicted a novel pathway for the mutagenic
tautomerization of the classical A?T DNA base pairs in the free state, the Watson
Crick A.T(WC), reverse Watson-Crick A.T(rWC), Hoogsteen A.T(H) and reverse
Hoogsteen A.T(rH) pairs, via sequential proton transfer accompanied by a
significant change in the mutual orientation of the bases. Quantum-mechanical
(QM) calculations were performed at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p)
level in vacuum phase, along with Bader's quantum theory of Atoms in Molecules
(QTAIM). These processes involve transition states (TSs) with quasi-orthogonal
structures (symmetry C1), which are highly polar, tight ion pairs (A-, N6H2
deprotonated)?(T+, O4/O2-protonated). Gibbs free energies of activation for the
A?T(WC) / A?T(rWC) <-> A*?T(rwWC) / A*?T(wWC) tautomeric transitions (~43.5
kcal?mol-1) are lower than for the A?T(H) / A?T(rH) <-> A*N7?T(rwH) / A*N7?T(wH)
tautomerisations (~53.0 kcal?mol-1) (rare tautomers are marked by an asterisk; w
wobble configured tautomerisation products). The (T)N3+H?N1-(A), (T)O4+H?N1-(A) /
(T)N3+H?N1-(A) and (T)O2+H?N1-(A) H-bonds are found in the transition states TSA
.T+A.T(WC)<->A*.T(rwWC) / TSA-.T+A.T(rWC)<->A*.T(wWC). However, in the transition
state TSA-.T+A.T(H)<->A*N7.T(rwH) / TSA-.T+A.T(rH)<->A*N7.T(wH), the (T)N3+H?N7
(A), (T)O4+H?N7-(A) / (T)N3+H?N7-(A) and (T)O2+H?N7-(A) H-bonds are supplemented
by the attractive (T)O4+/O2+?N6-(A) van der Waals contacts. It was demonstrated
that the products of the tautomerization of the classical A?T DNA base pairs
A*?T(rwWC), A*N7?T(rwH) and A*N7?T(wH) (symmetry Cs)-further transform via double
proton transfer into the energetically favorable wobble A?T*(rwWC), A?T*(rwH) and
A?T*O2(wH) base mispairs (symmetry Cs).
PMID- 29949603
TI - Network-based association analysis to infer new disease-gene relationships using
large-scale protein interactions.
AB - Protein-protein interactions integrated with disease-gene associations represent
important information for revealing protein functions under disease conditions to
improve the prevention, diagnosis, and treatment of complex diseases. Although
several studies have attempted to identify disease-gene associations, the number
of possible disease-gene associations is very small. High-throughput technologies
have been established experimentally to identify the association between genes
and diseases. However, these techniques are still quite expensive, time
consuming, and even difficult to perform. Thus, based on currently available data
and knowledge, computational methods have served as alternatives to provide more
possible associations to increase our understanding of disease mechanisms. Here,
a new network-based algorithm, namely, Disease-Gene Association (DGA), was
developed to calculate the association score of a query gene to a new possible
set of diseases. First, a large-scale protein interaction network was
constructed, and the relationship between two interacting proteins was calculated
with regard to the disease relationship. Novel plausible disease-gene pairs were
identified and statistically scored by our algorithm using neighboring protein
information. The results yielded high performance for disease-gene prediction,
with an F-measure of 0.78 and an AUC of 0.86. To identify promising candidates of
disease-gene associations, the association coverage of genes and diseases were
calculated and used with the association score to perform gene and disease
selection. Based on gene selection, we identified promising pairs that exhibited
evidence related to several important diseases, e.g., inflammation, lipid
metabolism, inborn errors, xanthomatosis, cerebellar ataxia, cognitive
deterioration, malignant neoplasms of the skin and malignant tumors of the
cervix. Focusing on disease selection, we identified target genes that were
important to blistering skin diseases and muscular dystrophy. In summary, our
developed algorithm is simple, efficiently identifies disease-gene associations
in the protein-protein interaction network and provides additional knowledge
regarding disease-gene associations. This method can be generalized to other
association studies to further advance biomedical science.
PMID- 29949604
TI - Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR
181b1 are not required for thymic development.
AB - MicroRNAs (miRNAs) have been shown to be key modulators of post-transcriptional
gene silencing in many cellular processes. In previous studies designed to
understand the role of miRNAs in thymic development, we globally deleted miRNA
exclusively in thymic epithelial cells (TECs), which are critical in thymic
selection. This resulted in the loss of stromal cells that instruct T cell
lineage commitment and affect thymocyte positive selection, required for mature T
cell development. Since murine miR-181 is expressed in the thymus and miR-181
deficiency disrupts thymocyte development, we first quantified and thereby
demonstrated that miR181a1 and miR181b1 are expressed in purified TECs. By
generating mice with TEC targeted loss of miR-181a1 and miR-181b1 expression, we
observed that neither TEC cellularity nor thymocyte number nor differentiation
was adversely affected. Thus, disrupted thymopoiesis in miR-181 deficient mice
was not due to miR-181 loss of expression in TECs. Importantly, in mice with
restricted TEC deficiency of miR-181a1 and miR-181b1, there were similar numbers
of mature T cells in the periphery in regards to frequencies, differentiation,
and function as compared to controls. Moreover miR-181a1 and miR-181b1 were not
required for maintenance of thymus integrity over time, as thymic involution was
not accelerated in gene-targeted mice. Taken together our data indicate that miR
181a1 and miR-181b1 are dispensable for TEC differentiation, their control of
thymocyte development and mature T cell export to and homeostasis within the
periphery.
PMID- 29949605
TI - Prevalence of brucellosis among patients attending Wau Hospital, South Sudan.
AB - Brucellosis is a zoonotic disease of public health importance; its prevalence
varies globally. In low-income countries, brucellosis is an endemic and neglected
disease affecting both animals and humans. This study was intended to establish
brucellosis sero-prevalence among patients attending Wau hospital, South Sudan.
Across sectional study, was done among randomly selected patients attending Wau
hospital. Data was collected using questionnaires and laboratory investigations.
Rose Bengal plate Test (RBPT), Serum agglutination test (SAT) and Competitive
Enzyme Linked Immuno Sorbent Assay (c-ELISA) was used in the analysis of blood
samples serially starting with RBPT which is more sensitive and least specific
then SAT. c-ELISA test which is most specific and less sensitive compared to RBPT
and SAT was then used to confirm presence of Brucella antibodies in the samples.
A total of 416 participants out of 1664 were enrolled to this study. The majority
of participants were between 7-to-76 years of age with mean age of 30.72 (SD+/-
12.83). The sero-positivity of patient's blood samples for brucellosis using c
ELISA was 23.3% (97/416) among patients presenting to Wau hospital. Socio
demographic characteristics, occupation, clinical signs of disease and types of
animals reared by animal owners showed no significant correlation with occurrence
of sero-positivity among patient's blood samples for brucellosis. While ethnicity
(Nilotic), knowledge of zoonotic disease, and consumption of animal urine were
statistically significant (p<0.05). The study found a high prevalence of
brucellosis among febrile patients attending Wau hospital general outpatient
clinic. There is need for co-ordination and collaboration between veterinary and
health sectors of government to help prevent and control brucellosis in the
region.
PMID- 29949606
TI - Prolactin selectively transported to cerebrospinal fluid from blood under
hypoxic/ischemic conditions.
AB - AIM: The aim of this study was to determine and to verify the correlation between
the amount of prolactin (PRL) levels in the blood and in the cerebrospinal fluid
(CSF) by various causes of death as an indicator for acute hypoxia in autopsy
cases. It is to confirm the cause of the change in prolactin level in CSF by in
vitro system. MATERIALS AND METHODS: In autopsy materials, the PRL levels in
blood from the right heart ventricle and in the CSF were measured by
chemiluminescent enzyme immunoassay, and changes in the percentage of PRL
positive cells in the pituitary gland were examined using an immunohistochemical
method. Furthermore, an inverted culture method was used as an in vitro model of
the blood-CSF barrier using epithelial cells of the human choroid plexus (HIBCPP
cell line) and SDR-P-1D5 or MSH-P3 (PRL-secreting cell line derived from
miniature swine hypophysis) under normoxic or hypoxic (5% oxygen) conditions, and
as an index of cell activity, we used Vascular Endothelial Growth Factor (VEGF).
RESULTS AND DISCUSSION: Serum PRL levels were not significantly different between
hypoxia/ischemia cases and other causes of death. However, PRL levels in CSF were
three times higher in cases of hypoxia/ischemia than in those of the other causes
of death. In the cultured cell under the hypoxia condition, PRL and VEGF showed a
high concentration at 10 min. We established a brain-CSF barrier model to clarify
the mechanism of PRL transport to CSF from blood, the PRL concentrations from
blood to CSF increased under hypoxic conditions from 5 min. These results
suggested that PRL moves in CSF through choroidal epithelium from blood within a
short time. PRL is hypothesized to protect the hypoxic/ischemic brain, and this
may be because of the increased transportation of the choroid plexus epithelial
cells.
PMID- 29949607
TI - Audio-tactile cues from an object's fall change estimates of one's body height.
AB - When we drop an object from our hands, we use internal models of both our body
height and object-motion to predict when it will hit the floor. What happens if
the sensory feedback finally received from the impact conflicts with this
prediction? The present study shows that such conflict results in changes in the
internal estimates of our body height: When the object people dropped takes
longer than expected to hit the floor, they report feeling taller and behave as
if their legs were longer. This provides the first evidence of cross-modal
recalibration of body-height representations as a function of changes in the
distant environment. Crucially, the recalibration results from a mismatch between
the predicted and actual outcome of an action, the ball's release and impact,
which are causally-related but separated in space and time. These results suggest
that implicit models of object-motion can interact with implicit and explicit
models of one's body height.
PMID- 29949608
TI - Longitudinal multiple case study on effectiveness of network-based dementia care
towards more integration, quality of care, and collaboration in primary care.
AB - INTRODUCTION: This study aimed to provide insight into the merits of DementiaNet,
a network-based primary care innovation for community-dwelling dementia patients.
METHODS: Longitudinal mixed methods multiple case study including 13 networks of
primary care professionals as cases. Data collection comprised continuously-kept
logs; yearly network maturity score (range 0-24), yearly quality of care
assessment (quality indicators, 0-100), and in-depth interviews. RESULTS:
Networks consisted of median nine professionals (range 5-22) covering medical,
care and welfare disciplines. Their follow-up was 1-2 years. Average yearly
increase was 2.03 (95%-CI:1.20-2.96) on network maturity and 8.45 (95%-CI:2.80
14.69) on quality indicator score. High primary care practice involvement and
strong leadership proved essential in the transition towards more mature networks
with better quality of care. DISCUSSION: Progress towards more mature networks
favored quality of care improvements. DementiaNet appeared to be effective to
realize transition towards network-based care, enhance multidisciplinary
collaboration, and improve quality of dementia care.
PMID- 29949609
TI - High CD90 (THY-1) expression positively correlates with cell transformation and
worse prognosis in basal-like breast cancer tumors.
AB - Breast cancer is the most prevalent cancer among women, with the basal-like
triple negative (TNBC) being the most agressive one, displaying the poorest
prognosis within the ductal carcinoma subtype. Due to the lack of adequate
molecular targets, the diagnosis and treatment of patients with the TNBC
phenotype has been a great challenge. In a previous work, we identified CD90/Thy
1 as being highly expressed in the aggressive high malignancy grade Hs578T basal
like breast tumor cell line, pointing to this molecule as a promising breast
tumor marker, which should be further investigated. Here, CD90 expression was
analyzed in human breast cancer samples and its functional role was investigated
to better assess the oncogenic nature of CD90 in mammary cells. Quantification of
CD90 expression in human breast cancer samples, by tissue microarray, showed that
high CD90 positivity correlates with metastasis and poor patient survival in the
basal-like subtype. The functional genetic approach, by overexpression in the
CD90 cDNA in a basal-like normal mammary cell line (MCF10A) and knockdown in a
highly malignant cell line (Hs578T), allowed us to demonstrate that CD90 is
involved with several cellular processes that lead to malignant transformation,
such as: morphological change, increased cell proliferation, invasiveness,
metastasis and activation of the EGFR pathway. Therefore, our results reveal that
CD90 is involved with malignant transformation in breast cancer cell lines and is
correlated with metastasis and poor patient survival in the basal-like subtype,
being considered as a promising new breast cancer target.
PMID- 29949610
TI - Monitoring the reproductive activity in captive bred female ball pythons (P.
regius) by ultrasound evaluation and noninvasive analysis of faecal reproductive
hormone (progesterone and 17beta-estradiol) metabolites trends.
AB - The royal python (Python regius) is commonly bred in captivity. To have a
successful breeding season, accurate monitoring of the reproductive activity is
necessary. The use of non-invasive monitoring methods in exotics is important in
order to minimize stress. For this purpose ultrasound has been anecdotally used
to monitor royal python reproductive activity. However, there is limited
information regarding the reproductive cycle of this species. The aim of the
present study is to monitor the female reproductive cycle of the royal python
using ultrasonography and gonadal steroid metabolite measurements in the faeces.
The reproductive activity of one hundred twenty-nine adult female P. regius was
examined during two consecutive years. We performed brief scans on non
anaesthetized snakes using a portable ultrasound system and a 10-12 MHz linear
array transducer (MyLabTM 30 Gold, Esaote). Ultrasound features, dimension and
echogenicity of the reproductive structures were determined. During the second
reproductive cycle, the hormonal profiles of 30 animals were also evaluated, with
a monthly collection of faecal samples. These samples were classified according
to reproductive stage, as identified by ultrasonographic examination, and the
mean faecal progesterone and 17beta-estradiol levels were calculated using the
results from an enzyme-linked immunosorbent assay (ELISA). Progesterone levels
increased during the reproductive cycle. Estradiol levels showed greater
variability, although they appeared to increase before coupling when compared to
the levels between coupling and egg laying. The present study suggests that it is
possible to identify different phases in the female royal python reproductive
cycle: anovulatory phase, transition, folliculogenesis and embryogenesis.
Ultrasound is also useful for identifying follicular regression or slugs. Gonadal
steroid metabolite measurements from the faeces could help integrate reproductive
information. The use of ultrasonography in addition to the steroid metabolite
measurement in the faeces gives an accurate picture of ovarian activity in
captive adult female royal pythons.
PMID- 29949611
TI - Health-related regional and neighborhood correlates of sexual minority
concentration: A systematic review.
AB - BACKGROUND: A growing literature explores spatial patterns of regional and
neighborhood correlates of sexual minority (e.g., lesbian, gay, bisexual)
concentration. Such patterns have implications for health and wellbeing if there
are differences in health-promoting or health-hindering resources in
neighborhoods or regions. We conducted a systematic review to assess sexual
minority concentration in relation to area unit characteristics. METHODS: We
included only records published after 1973 and made no exclusions by geography or
language. We searched 11 databases (Academic Search Complete, CINAHL, Embase,
GeoBase, GeoRef, LGBT Life, PsycINFO, PubMed/MEDLINE, Scopus, Sociological
Abstracts, Web of Science) on November 19-21, 2016. We searched reference lists
of included records. We used the following inclusion criteria: (1) Record is a
quantitative study (that is, it uses statistics to describe or associate two or
more variables); (2) Record is about (a) migration or internal migration of, (b)
area unit selection by, or (c) concentration of sexual minority people (defined
by identity, behavior, or attraction); (3) Criterion 2 is linked to the
characteristics of regions or neighborhoods (at any spatial scale). RESULTS: Dual
independent coding resulted in 51 records meeting inclusion criteria from the
original pool of 5,591. From these records, we identified the 647 reported
results linking sexual minority concentration with area unit characteristics. Of
these, 132 were unadjusted relationships between sexual minority concentration
and four theory-informed domains of neighborhood influence on health. We
identified greater concentration of sexual minorities in regions with more
resources and in more urban regions. A limited but troubling literature at the
neighborhood level suggested potentially higher concentrations of sexual
minorities in neighborhoods with fewer resources. CONCLUSIONS: There are
substantial gaps in the literature. We discuss the implications of our findings
and gaps in relation to key theories of sexual minority health. REGISTRATION: The
review was not registered with PROSPERO because it was not eligible for
registration at the time of the research project's initiation due to the outcome
of interest.
PMID- 29949613
TI - Fire benefits flower beetles in a Mediterranean ecosystem.
AB - Despite the abundance of plants that benefit from fire in Mediterranean
ecosystems, little is known about the possible presence of fire-favoured insects
(other than bark beetles). For two years we sampled invertebrates after two large
wildfires in eastern Spain and demonstrate that two flower beetle species,
Protaetia morio and P. oblonga (Cetoniidae), show a pyrophilous behaviour. These
beetles were much more numerous after the fires than in unburnt plots around the
fire perimeter; in addition, these species tended to increase in number with the
distance from the fire perimeter and with fire recurrence, especially P. morio.
These results were maintained for the two postfire years sampled. The results for
the beetles do not support the hypothesis of postfire colonization, but that
local populations survived the fire as eggs or larvae protected in the soil
(endogenous persistence). We propose that the increase in population size
(compared with unburnt zones) could be driven by the reduction of their predator
populations, as vertebrates that feed on these beetles were disfavoured by fire.
That is, the results suggest that these flower beetle species benefit from fire
because fire disrupts antagonistic interactions with their predators (predation
release hypothesis). Given the omnipresence of small mammals, soil insects, and
fires, the processes described here are likely to be general but unexplored.
PMID- 29949612
TI - Clipperton Atoll as a model to study small marine populations: Endemism and the
genomic consequences of small population size.
AB - Estimating population sizes and genetic diversity are key factors to understand
and predict population dynamics. Marine species have been a difficult challenge
in that respect, due to the difficulty in assessing population sizes and the open
nature of such populations. Small, isolated islands with endemic species offer an
opportunity to groundtruth population size estimates with empirical data and
investigate the genetic consequences of such small populations. Here we focus on
two endemic species of reef fish, the Clipperton damselfish, Stegastes baldwini,
and the Clipperton angelfish, Holacanthus limbaughi, on Clipperton Atoll,
tropical eastern Pacific. Visual surveys, performed over almost two decades and
four expeditions, and genetic surveys based on genomic RAD sequences, allowed us
to estimate kinship and genetic diversity, as well as to compare population size
estimates based on visual surveys with effective population sizes based on
genetics. We found that genetic and visual estimates of population numbers were
remarkably similar. S. baldwini and H. limbaughi had population sizes of
approximately 800,000 and 60,000, respectively. Relatively small population sizes
resulted in low genetic diversity and the presence of apparent kinship. This
study emphasizes the importance of small isolated islands as models to study
population dynamics of marine organisms.
PMID- 29949614
TI - Genetic diversity and population structure of three traditional horse breeds of
Bhutan based on 29 DNA microsatellite markers.
AB - The genetic variability and population structure of three Bhutanese traditional
horse breeds were assessed through genotyping of 74 horses (Boeta 25, Sharta 14
and Yuta 35) for 29 microsatellite DNA loci. Altogether, 282 alleles were
detected across 29 polymorphic loci. The allelic diversity (NE) (Boeta 4.94;
Sharta 4.65; Yuta 5.30) and gene diversities (HE) (Boeta 0.78; Sharta 0.77; Yuta
0.79) were high. None of the breeds deviated significantly from the Hardy
Weinberg equilibrium. There was no sign of significant population bottleneck for
all the breeds. The inbreeding estimates (FIS) of the breeds were low (Boeta
0.023; Sharta 0.001; Yuta 0.021). Analysis of molecular variance showed 0.6% of
the total genetic variation among breeds, 1.9% among individuals and 97.5% within
individuals. The global FIT, FST, and FIS estimates for the population were
0.025, 0.006 and 0.019 respectively. The analysis of population structure failed
to distinguish subpopulations in traditional horses and this was supported by a
high genetic exchange among the breeds. Overall, the results of this study
suggest a rich genetic diversity in the traditional horse despite a very low
genetic differentiation among the breeds in Bhutan.
PMID- 29949615
TI - Quaternion wavelet transform based full reference image quality assessment for
multiply distorted images.
AB - Most of real-world image distortions are multiply distortion rather than single
distortion. To address this issue, in this paper we propose a quaternion wavelet
transform (QWT) based full reference image quality assessment (FR IQA) metric for
multiply distorted images, which jointly considers the local similarity of phase
and magnitude of each subband via QWT. Firstly, the reference images and
distorted images are decomposed by QWT, and then the similarity of amplitude and
phase are calculated on each subband, thirdly the IQA metric is constructed by
the weighting method considering human visual system (HVS) characteristics, and
lastly the scores of each subband are averaged to get the quality score of test
image. Experimental results show that the proposed method outperforms the state
of art in multiply distorted IQA.
PMID- 29949616
TI - Causality and preventability assessment of adverse drug reactions and adverse
drug events of antibiotics among hospitalized patients: A multicenter, cross
sectional study in Lahore, Pakistan.
AB - BACKGROUND AND OBJECTIVES: Adverse drug events (ADEs) are the fifth leading cause
of death and thus responsible for a large number of hospital admissions in all
over the globe. This study was aimed to assess the antibiotics associated
preventability of ADEs and causality of adverse drug reactions (ADRs) among
hospitalized patients. METHODS: A prospective, cross-sectional, observational
study was conducted in four tertiary care public sector hospitals of Lahore,
Pakistan. Study population consisted of hospitalized patients who were prescribed
with one or more antibiotics. Data were collected between 1st January, 2017 and
31st June, 2017 from 1,249 patients (384 patients aged <= 18 years and 865
patients aged >18 years). Schumock and Thornton scale was used to assess the
preventability of the ADEs. Medication errors (MEs) that caused preventable ADEs
were assessed by MEs tracking form while Naranjo score was used to evaluate the
causal relation of ADRs with the antibiotics. Statistical Package for the Social
Sciences (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.)
and Microsoft Excel (MS Office, 2010) were used for data analysis. RESULTS: 2,686
antibiotics were prescribed to 1,249 patients. Among them, fluoroquinolones
(11.8%), macrolides (11.6%) and cephalosporins (10.9%) were the most frequently
prescribed antibiotics. The most affected organ system by antibiotics associated
ADEs was gastrointestinal tract. A total of 486 ADEs were found. The
preventability assessment revealed that most of the ADEs (58.4%) were preventable
(43.6% of the ADEs were definitely preventable while 14.8% were probably
preventable) and caused by MEs including wrong drug (40.1%) and monitoring errors
(25.0%), during the stage of physician ordering (22.2%) and patient monitoring
(21.1%). The errors were caused due to non-adherence of policies (38.4%) and lack
of information about antibiotics (32%). Most of the non-preventable ADEs or ADRs
among adults and children were "probable" (35.5%) and "possible" (35.8%),
respectively. Logistic regression analysis revealed that ADEs were significantly
less among females (OR = 0.047, 95%CI = 0.018-0.121, p-value = <0.001), patients
aged 18-52 years (OR = 0.041, 95%CI = 0.013-0.130, p-value = <0.001),
tuberculosis patients (OR = 0.304, 95%CI = 0.186-0.497, p-value = <0.001),
patients with acute respiratory tract infections (OR = 0.004, 95%CI = 0.01-0.019,
p-value = <0.001) and among the patients prescribed with 2 antibiotics per
prescription (OR = 0.455, 95%CI = 0.319-0.650, p-value = <0.001). CONCLUSION:
According to preventability assessment most of the ADEs were definitely
preventable and caused by MEs due to non-adherence of policies and lack of
information about antibiotics. The causality assessment of non-preventable ADEs
showed that most of the ADRs were probable and possible.
PMID- 29949617
TI - Land-based drip-irrigated culture of Ulva compressa: The effect of culture
platform design and nutrient concentration on biomass production and protein
content.
AB - This work developed a laboratory prototype methodology for cost-effective, water
sparing drip-irrigation of seaweeds, as a model for larger-scale, on-land
commercial units, which we envision as semi-automated, inexpensive polyethylene
sheet-covered bow-framed greenhouses with sloping plastic covered floors, water
collecting sumps, and pumped recycling of culture media into overhead low
pressure drip emitters. Water droplets form on the continually wetted interior
plastic surfaces of these types of greenhouses scattering incoming solar
radiation to illuminate around and within the vertically-stacked culture
platforms. Concentrated media formulations applied through foliar application
optimize nutrient uptake by the seaweeds to improve growth and protein content of
the cultured biomass. An additional attribute is that seaweed growth can be
accelerated by addition of anthropogenic CO2-containing industrial flue gases
piped into the head-space of the greenhouse to reuse and recycle CO2 into useful
algal biomass. This demonstration tested three different drip culture platform
designs (horizontal, vertical and slanted) and four increasing fertilizer media
concentrations (in seawater) for growth, areal productivity, and thallus protein
content of wild-collected Ulva compressa biomass, against fully-submerged
controls. Cool White fluorescent lights provided 150-200 MUmol photon m-2 s-1
illumination on a 12/12 hr day/night cycle. Interactive effects we tested using a
four-level single factorial randomized block framework (p<0.05). Growth rates and
biomass of the drip irrigation designs were 3-9% day-1 and 5-18 g m-2 day-1
(d.w.) respectively, whereas the fully-submerged control group grew better at 8
11% per day with of 20-30 g m-2 day-1, indicating further optimization of the
drip irrigation methodology is needed to improve growth and biomass production.
Results demonstrated that protein content of Ulva biomass grown using the
vertically-oriented drip culture platform and 2x fertilizer concentrations
(42:16:36 N:P:K) was 27% d.w., approximating the similarly-fertilized control
group. The drip methodology was found to significantly improve gas and nutrient
mass transfer through the seaweed thalli, and overall, the labor- and-energy
saving methodology would use a calculated 20% of the seawater required for
conventional on-land tank-based tumble culture.
PMID- 29949618
TI - Serum MMP-2 as a potential predictive marker for papillary thyroid carcinoma.
AB - OBJECTIVE: The prevalence of papillary thyroid carcinoma (PTC) is rising rapidly.
However, there are no reliable serum biomarkers for PTC. This study aimed to
investigate the validity of preoperative serum matrix metalloproteinase-2 (MMP-2)
as a biomarker for predicting prognosis of PTC after total or partial
thyroidectomy. METHODS: Male patients with PTC or a benign thyroid nodule (BTN)
and healthy controls (HCs) were retrospectively included. Receiver operating
characteristic (ROC) curves were constructed to evaluate the performance of
preoperative serum MMP-2 in diagnosing PTC, predicting lymph node metastasis
(LNM), and predicting structurally persistent/recurrent disease (SPRD).
Multivariate logistic regression and Cox regression were applied to identify
independent risk factors for SPRD. RESULTS: The preoperative serum MMP-2
concentration in the PTC group was higher than those in BTN and HC groups. The
concentration of postoperative serum MMP-2 decreased in comparison with pre
operation. ROC curves showed that serum MMP-2 could differentially diagnose PTC
from BTN at the cutoff value of 86.30 ng/ml with an area under the curve (AUC) of
0.905 and could predict central LNM (CLNM) at the cutoff value of 101.55 ng/ml
with an AUC of 0.711. Serum MMP-2 >=101.55 ng/ml, age >=45 years, and advanced
TNM stage were independent risk factors for CLNM. Patients with SPRD had a higher
median MMP-2 level (149.22 ng/ml) than patients without SPRD (104.55 ng/ml).
Serum MMP-2 at the cutoff value of 144.04 ng/ml could predict SPRD in PTC
patients with an AUC of 0.803. Advanced TNM stage and serum MMP-2 >=144.04 ng/ml
were independent risk factors for SPRD. Patients with serum MMP-2 >=144.04 ng/ml
had a worse clinical outcome than those with MMP-2 <144.04 ng/ml. CONCLUSION:
Preoperative serum MMP-2 may serve as a biomarker for diagnosing PTC and a
predictive indicator for LNM and SPRD in male patients with PTC.
PMID- 29949619
TI - Central precocious puberty in Boston boys: A 10-year single center experience.
AB - OBJECTIVE: Recent studies in the US and abroad suggest that boys are undergoing
puberty at a younger age. It is unknown if this secular trend extends to boys
with central precocious puberty (CPP), who sit at the extreme end of the pubertal
spectrum, and if neuroimaging should remain a standard diagnostic tool. STUDY
DESIGN: Retrospective chart review of all boys with CPP seen by Endocrinology at
a US pediatric hospital from 2001-2010. RESULTS: Fifty boys had pubertal onset at
an average age of 7.31 years (95CI 6.83-7.89), though many did not present until
nearly one year thereafter, by which time 30% were mid-to-late pubertal. Boys
were predominantly non-Hispanic White and 64% were overweight/obese. The majority
(64%) of boys had neurogenic CPP (CNS-CPP) with neurofibromatosis type I being
the most common diagnosis. Diagnosis of CPP led to discovery of a neurogenic
lesion in only 3 of 32 (9%) CNS-CPP cases. The remaining boys, with idiopathic
CPP (36%), were indistinguishable from those with CNS-CPP aside from four boys
who endorsed a family history of PP (22% vs. 0% among CNS-CPP cases).
Importantly, there was no change in the incidence of male CPP after accounting
for the increase in clinic volume during this time period. CONCLUSION: In this
contemporary Boston-based cohort of 50 boys with CPP, most cases were neurogenic,
consistent with older literature. Several idiopathic cases had a family history
of PP but were otherwise indistinguishable from CNS-CPP cases. Thus, neuroimaging
remains a critical diagnostic tool. We find no evidence for an increase in the
prevalence of male CPP.
PMID- 29949620
TI - Micro RNA clusters in maternal plasma are associated with preterm birth and
infant outcomes.
AB - The current study examined micro RNA (miRNAs) clusters from the maternal plasma
to determine their association with preterm birth (PTB) and infant birth
outcomes. A subsample of 42 participants who spontaneously delivered either
preterm (<=37 weeks) or term was selected from a parent sample of 515 pregnant
Mexican American women. Plasma samples and prenatal data were collected at a
single mid-gestation time point (22-24 weeks' gestation) and birth outcomes were
obtained from medical records after delivery. Circulating miRNAs were analyzed by
qPCR. When miRNAs were grouped according to chromosomal cluster rather than
expression level, individual miRNAs correlated strongly with other individual
miRNAs within their respective genomic locus. miRNAs from the c19mc cluster
negatively correlated with c14mc miRNAs, and this relationship was more
pronounced in PTB. Clusters c14mc was negatively associated with length of
gestation; while the c19mc was positively associated with length of gestation and
infant head circumference. Together, these findings suggest that groups of miRNAs
from common chromosomal clusters, rather than individual miRNAs, operate as co
regulated groups of signaling molecules to coordinate length of gestation and
infant outcomes. From this evidence, differences in cluster-wide expression of
miRNAs are involved in spontaneous PTB.
PMID- 29949621
TI - The timing of energy allocation to reproduction in an important group of marine
consumers.
AB - Organisms may energetically finance reproductive effort using energy stored prior
to the reproductive period (termed capital breeders) or using energy acquired
during the reproductive period (termed income breeders). The specific strategy
used has implications for population dynamics as well as for the response to
environmental variation. Crabs and other crustaceans have generally been assumed
to be capital breeders. Here I demonstrate an experimental procedure used to
determine whether crabs are capable of using an income breeding strategy. I then
examine data from several published studies from a range of crab species across a
broad phylogenetic spectrum that conducted similar experiments to look for
evidence of income breeding strategy. I show that income breeding does occur in
crabs, but that it appears to be taxon-specific. In particular, I show that
income breeding occurs in two species from the family Portunidae, but fail to
find evidence for income breeding in other taxa examined. This finding has a
range of implications for this ecologically and economically important group of
consumers, including implications for their response to human-induced
environmental change, their response to fishing pressure, and best practices for
aquaculture. The implications of breeding strategy in crabs likely depends on
phylogeny (morphology) and ecology, both of which influence the space available
for energy storage inside the carapace.
PMID- 29949622
TI - Genome-wide association mapping in bread wheat subjected to independent and
combined high temperature and drought stress.
AB - Most investigations to date aiming to identify the genetic basis of the stress
response of wheat (Triticum aestivum L.) have focused on the response to single
stress agents such as high temperature or drought, even though in the natural
situation, these stresses tend often to occur together. Here, a panel of 108
spring type bread wheat cultivars was phenotyped for 15 yield and yield related
traits for two years (2014/15 and 2015/16) under non-stressed conditions, under
high temperature stress, under drought and under a combined high temperature and
drought regime. The mean loss in grain yield caused by all stress regimes was
51.33%. Analysis of variance (ANOVA) of yield trait showed significant
differences among genotypes environments and their interactions (G*E). All the
studied traits had higher heritability values which ranged from 0.35-0.94 under
[C], 0.58-0.95 under [D], 0.62-0.93 under [H] and 0.60-0.95 under [HD]. GWAS was
performed by using 9,646 informative SNP markers and based on these polymorphic
SNPs population structure analysis divided whole germplasm into five major sub
populations. Mixed model association analysis detected 503 marker-trait
associations (MTAs) at P <=0.001 while 329 MTAs crossed FDR <= 0.05 for all
traits with phenotypic variances (R2) ranged from 24.83% to 12.51%. Seven new
pleiotropic SNPs on chromosome 7D and IAAV8258 (86.91cM) and
wsnp_Ex_c7168_12311649 (57.93cM) on chromosome 5A were most stable association in
present study. Furthermore, candidate genes Psy and Sr25 (TG0040) were also
significant in present study, these genes were previously mapped on 7A and 7D.
The region on 7D was assiociated with 7DL.7Ag translocation from Lophopyrum
carring rust resistance Yr16 and many other genes. Similarly region on chromosome
7A which was associated with Psy gene was linked with grain yellow pigment
content QTLs. Favourable alleles controlling grain yield were of vital importance
and incorporation of these alleles after validation through marker assisted
selection and fine mapping could be helpful in wheat yield improvement stress and
non-stress conditions.
PMID- 29949624
TI - Predicting mortality with the international classification of disease injury
severity score using survival risk ratios derived from an Indian trauma
population: A cohort study.
AB - BACKGROUND: Trauma is predicted to become the third leading cause of death in
India by 2020, which indicate the need for urgent action. Trauma scores such as
the international classification of diseases injury severity score (ICISS) have
been used with great success in trauma research and in quality programmes to
improve trauma care. To this date no valid trauma score has been developed for
the Indian population. STUDY DESIGN: This retrospective cohort study used a
dataset of 16047 trauma-patients from four public university hospitals in urban
India, which was divided into derivation and validation subsets. All injuries in
the dataset were assigned an international classification of disease (ICD) code.
Survival Risk Ratios (SRRs), for mortality within 24 hours and 30 days were then
calculated for each ICD-code and used to calculate the corresponding ICISS. Score
performance was measured using discrimination by calculating the area under the
receiver operating characteristics curve (AUROCC) and calibration by calculating
the calibration slope and intercept to plot a calibration curve. RESULTS:
Predictions of 30-day mortality showed an AUROCC of 0.618, calibration slope of
0.269 and calibration intercept of 0.071. Estimates of 24-hour mortality
consistently showed low AUROCCs and negative calibration slopes. CONCLUSIONS: We
attempted to derive and validate a version of the ICISS using SRRs calculated
from an Indian population. However, the developed ICISS-scores overestimate
mortality and implementing these scores in clinical or policy contexts is not
recommended. This study, as well as previous reports, suggest that other scoring
systems might be better suited for India and other Low- and middle-income
countries until more data are available.
PMID- 29949623
TI - Vasodilator effects of dehydroepiandrosterone (DHEA) on fetal pulmonary
circulation: An experimental study in pregnant sheep.
AB - Persistent pulmonary hypertension (PPHN) remains a severe complication of the
transition to extra-uterine life with significant morbidity and mortality in the
newborns. Dehydroepiandrosterone (DHEA) represents a new pharmacological agent
with vascular effects, including improvement of PPHN in several animal models. We
hypothesized that DHEA could decrease pulmonary vascular resistance (PVR) in the
pulmonary circulation of fetal sheep. We studied the effect of intravenous
infusion of DHEA in fetal lambs using chronically instrumented sheep at 128 days
of gestation. PVR was computed before and after intravenous infusion of
increasing doses of DHEA. We assessed pre-treatment by L-nitroarginine, an
inhibitor of NO production. Blood gases and doses of DHEA were measured in both
sheep and fetus before/after DHEA infusion. Intravenous infusion of DHEA had a
vasodilator effect with a significant decrease in PVR (respectively -11%, -14%
and -36% after infusion of 6, 12 and 24 mg DHEA, p<0.01) without damaging effects
on systemic circulation or on blood gases. The inhibitory effect of pre-treatment
with L-nitroarginine resulted in a significant increase in PVR. We demonstrated a
potent vasodilator effect of DHEA on fetal pulmonary circulation without
deleterious effects. DHEA might represent a new treatment for PPHN.
PMID- 29949625
TI - Diallel genetic analysis for multiple traits in eggplant and assessment of
genetic distances for predicting hybrids performance.
AB - Evaluation and prediction of the performance of hybrids is important in eggplant
(Solanum melongena) breeding. A set of 10 morphologically highly diverse eggplant
parents, including nine inbred S. melongena and one weedy S. insanum accessions,
were intercrossed according to a half-diallel mating design without reciprocals
to obtain 45 hybrids. Parents and hybrids were evaluated for 14 morphological and
agronomic conventional descriptors and 14 fruit morphometric traits using Tomato
Analyzer. Genetic distances among parents were estimated with 7,335 polymorphic
SNP markers. Wide ranges of variation and significant differences were observed
in the set of 55 genotypes for all traits, although the hybrids group had
significantly higher vigour and yield than parents. General and specific
combining abilities (GCA and SCA) were significant for most (GCA) or all (SCA)
traits, although a wide variation was obtained for GCA/SCA ratios. Many relevant
traits associated to vigour and yield had low GCA/SCA ratios and narrow-sense
heritability (h2) values, while the reverse occurred for most fruit shape
descriptors. Broad-sense heritability (H2) values were generally high,
irrespective of GCA/SCA ratios. Significant correlations were found between
traits related to size of leaf, flower and fruit, as well as among many fruit
morphometric traits. Genetic distances (GD) among parents were coherent with
their phylogenetic relationships, but few significant and generally low
correlations were found between GD and hybrid means, heterosis or SCA. The
results provide relevant information for developing appropriate strategies for
parent selection and hybrid development in eggplant and suggest that GD among
parents have limited value to predict hybrid performance in this crop.
PMID- 29949626
TI - Multi-trait multi-environment Bayesian model reveals G x E interaction for
nitrogen use efficiency components in tropical maize.
AB - Identifying maize inbred lines that are more efficient in nitrogen (N) use is an
important strategy and a necessity in the context of environmental and economic
impacts attributed to the excessive N fertilization. N-uptake efficiency (NUpE)
and N-utilization efficiency (NUtE) are components of N-use efficiency (NUE).
Despite the most maize breeding data have a multi-trait structure, they are often
analyzed under a single-trait framework. We aimed to estimate the genetic
parameters for NUpE and NUtE in contrasting N levels, in order to identify
superior maize inbred lines, and to propose a Bayesian multi-trait multi
environment (MTME) model. Sixty-four tropical maize inbred lines were evaluated
in two experiments: at high (HN) and low N (LN) levels. The MTME model was
compared to single-trait multi-environment (STME) models. Based on deviance
information criteria (DIC), both multi- and single-trait models revealed
genotypes x environments (G x E) interaction. In the MTME model, NUpE was found
to be weakly heritable with posterior modes of heritability of 0.016 and 0.023
under HN and LN, respectively. NUtE at HN was found to be highly heritable
(0.490), whereas under LN condition it was moderately heritable (0.215). We
adopted the MTME model, since combined analysis often presents more accurate
breeding values than single models. Superior inbred lines for NUpE and NUtE were
identified and this information can be used to plan crosses to obtain maize
hybrids that have superior nitrogen use efficiency.
PMID- 29949627
TI - Patient reported measures of informed consent for clinical trials: A systematic
review.
AB - INTRODUCTION: The subjective assessment of the adequacy of informed consent for
clinical trials, and the potential difficulties associated with it, has led
several studies to develop objective measures of informed consent for clinical
trials. These objective measures of informed consent are often specific to a
particular population or clinical condition and largely focus on understanding of
(some or all of) the key elements of informed consent. Many of the developed
tools are study-specific, but some validated measures exist. Of these validated
measures, those which are reported by participants are of particular interest.
Whether these objective tools conceptualize and measure informed consent in the
same way is not known. As such, it is not clear whether meta-analyzing data from
studies reporting different tools is worthwhile. The aim of this systematic
review was to critically appraise the evidence on the overall conceptualisation
and item content of validated patient reported measures of informed consent for
clinical trials, and to identify core domains of potential importance for
informed consent. METHODS: A systematic search of the literature was conducted to
identify relevant articles that described the development, and/or validation, of
patient-reported measures of adequacy of informed consent for randomised
controlled trials. Data was synthesised by classifying the items identified into
domains and sub-domains which were determined by the nomenclature reported in
included studies. Both for descriptions of included studies and of the
instruments reported in those studies, descriptive statistics were used to
describe general information and instrument detail. A narrative synthesis of the
instruments and their inter-related domains and subdomains was conducted to
identify areas of both convergence and divergence. RESULTS: The search identified
8193 citations. After screening titles and abstracts, 29 full text articles were
retrieved for further assessment. Of these 29, 14 complied with our pre-specified
inclusion criteria with 15 not being eligible. Of the 14 instruments, three
explicitly reported a theoretical or conceptual framework underpinning their
development, a further three implicitly referred to the 'conceptual dimensions of
informed consent' or 'principles of research ethics' as informing their
development and eight reported no guiding theoretical framework. Only three of
the 14 studies reported patient or public involvement in the development of the
tool. One hundred and seventy nine items were included across the 14 instruments.
The primary focus of the instruments was on understanding. Five core domains were
identified which included: Autonomy; Consequences; Expectations; Purpose; and
Individualisation. There was substantial variability in the coverage of different
domains across measures. CONCLUSIONS: This study demonstrated the variability in
the theoretical underpinning, development and domain coverage of existing patient
reported measures of informed consent for clinical trials. The conceptualisation
of informed consent could benefit from being extended from a narrow focus on
understanding to include broader considerations of decision-making. Meaningful
involvement of potential trial participants during development of measures
critical for tool relevance is also lacking. The identification of the key
domains relevant to all stakeholders which could be measured to assess the
informed consent process for clinical trials is needed.
PMID- 29949628
TI - The crystallization additive hexatungstotellurate promotes the crystallization of
the HSP70 nucleotide binding domain into two different crystal forms.
AB - The use of the tellurium-centered Anderson-Evans polyoxotungstate [TeW6O24]6-
(TEW) as a crystallization additive has been described. Here, we present the use
of TEW as an additive in the crystallization screening of the nucleotide binding
domain (NBD) of HSP70. Crystallization screening of the HSP70 NBD in the absence
of TEW using a standard commercial screen resulted in a single crystal form. An
identical crystallization screen of the HSP70 NBD in the presence of TEW resulted
in both the "TEW free" crystal form and an additional crystal form with a
different crystal packing. TEW binding was observed in both crystal forms, either
as a well-defined molecule or in overlapping alternate positions suggesting
translational disorder. The structures were solved by both molecular replacement
and single wavelength anomalous diffraction (SAD) using the anomalous signal of a
single bound molecule of TEW. This study adds one more example of TEW binding to
a protein and influencing its crystallization behavior.
PMID- 29949629
TI - Chronic kidney disease in patients at high risk of cardiovascular disease in the
United Arab Emirates: A population-based study.
AB - Chronic kidney disease has become an increasingly significant clinical and public
health issue, accounting for 1.1 million deaths worldwide. Information on the
epidemiology of chronic kidney disease and associated risk factors is limited in
the United Arab Emirates. Therefore, this study aimed to evaluate the incidence
and causes of chronic kidney disease stages 3-5 in adult United Arab Emirates
nationals with or at high risk of cardiovascular disease. This retrospective
study included 491 adults with or at high risk of cardiovascular disease
(diabetes mellitus or associated clinical disease) who attended outpatient
clinics at a tertiary care hospital in Al-Ain, United Arab Emirates. Estimated
glomerular filtration rate was assessed every 3 months from baseline to June 30,
2017. Chronic kidney disease stages 3-5 were defined as an estimated glomerular
filtration rate < 60 mL/min/1.73 m2 for >= 3 months. Multivariable Cox's
proportional hazards analysis was used to determine the independent risk factors
associated with developing chronic kidney disease stages 3-5. The cumulative
incidence of chronic kidney disease stages 3-5 over a 9-year period was 11.4%
(95% confidence interval 8.6, 14.0). The incidence rate of these disease stages
was 164.8 (95% confidence interval 121.6, 207.9) per 10,000 person-years. The
independent risk factors for developing chronic kidney disease stages 3-5 were
older age, history of coronary heart disease, history of diabetes mellitus, and
history of smoking. These data may be useful to develop effective strategies to
prevent chronic kidney disease development in high-risk United Arab Emirates
nationals.
PMID- 29949630
TI - Choosing the perfect shot - The loaded narrative of imagery in online news
coverage of vaccines.
AB - Images in health communication have been shown to affect perspectives and
attitudes towards health issues including vaccination. We seek to quantify the
frequency of images used in online news coverage of vaccines that may convey
varying sentiments about vaccination. To capture a breadth of vaccine-related
news coverage, including international sources, we searched the following terms
in Google News Archives: "autism and vaccine", "flu and vaccine", and "measles
and Disneyland". We developed a coding tool that classified images as negative
(eg, screaming child), positive (eg, happy child), neutral (eg, vaccine vial), or
irrelevant (eg, picture of journalist). All images were coded independently by
two researchers and discussed for consensus. We analyzed 734 images. Of the
images which featured vaccines and/or a medical encounter (322), 28% had negative
features and 30% had positive features. The remaining 137 images (43%) were
neutral. There was no statistically significant difference between proportions of
negative and positive imagery for each pair of search terms, which may be a
reflection of random image selection. Ultimately, nearly one in eight images
included in vaccine-related news coverage contains negative features which may be
selected without careful consideration of the potential negative impact on public
health initiatives regarding vaccination.
PMID- 29949631
TI - Comparing catch efficiency of five models of pot for use in a Newfoundland and
Labrador cod fishery.
AB - Sustainability of commercial fisheries is best achieved when fishing gears are
selective and have low impacts on bottom habitat. Pots (baited traps) are a
fishing technology that typically has lower impacts than many other industrial
gears. In this study we compared the efficiency of five models of pots (baited
traps) designed to catch Atlantic cod (Gadus morhua) for use in Newfoundland and
Labrador (NL)'s expanding cod fishery. We compared catch per unit effort (CPUE)
and total lengths of cod across each pot type, as well as bycatch rates of each
model. All pot types were successful at catching cod, but two models (the
modified Newfoundland pot, and a four-entrance pot of our design) had highest
CPUE. Specifically, we found that modifying Newfoundland pots increased their
CPUE by 145% without a corresponding increase in bycatch. None of the pot types
produced substantial amounts of bycatch. This study demonstrated that potting
gear is an effective way to catch cod in NL, and that there is flexibility in
which pot fishers can use, depending on the layout of their fishing vessel.
PMID- 29949632
TI - Human papillomavirus (HPV) genotype distribution in penile carcinoma: Association
with clinic pathological factors.
AB - BACKGROUND: Penile carcinoma (PC) is a rare, highly mutilating disease, common in
developing countries. The evolution of penile cancer includes at least two
independent carcinogenic pathways, related or unrelated to HPV infection.
OBJECTIVES: To estimate the prevalence, identify HPV genotypes, and correlate
with clinicopathological data on penile cancer. METHODS: A retrospective cohort
study involving 183 patients with PC undergoing treatment in a referral hospital
in Goiania, Goias, in Midwestern Brazil, from 2003 to 2015. Samples containing
paraffin embedded tumor fragments were subjected to detection and genotyping by
INNO-LiPA HPV. The clinicopathological variables were subjected to analysis with
respect to HPV positivity and used prevalence ratio (PR), adjusted prevalence
ratio (PRa) and 95% confidence interval (CI) as statistical measures. RESULTS:
The prevalence of HPV DNA in PC was 30.6% (95% CI: 24.4 to 37.6), high-risk HPV
24.9% (95% CI: 18.9 to 31.3), and 62.5% were HPV 16. There was a statistical
association between the endpoints HPV infection and HPV high risk, and the
variable tumor grade II-III (p = 0.025) (p = 0.040), respectively. There was no
statistical difference in disease specific survival at 10 years between the HPV
positive and negative patients (p = 0.143), and high and low risk HPV (p =
0.325). CONCLUSIONS: The prevalence of HPV infection was 30.6%, and 80.3% of the
genotypes were identified as preventable by anti-HPV quadrivalent or nonavalent
vaccine. HPV infections and high-risk HPV were not associated with penile
carcinoma prognosis in this study.
PMID- 29949633
TI - Correlates of long-acting reversible contraception uptake among rural women in
Guatemala.
AB - OBJECTIVE: In many low-resource settings around the world utilization of long
acting reversible contraception (LARC) is low, in part due to access barriers. We
sought to explore LARC utilization patterns as well as factors associated with
LARC initiation by women seeking contraception in rural Guatemala from a program
working to reduce contraception access barriers. STUDY DESIGN: We analyzed data
from a program that provides family planning in six remote, primarily indigenous,
villages in Guatemala with limited access to alternative health services. Methods
are free and delivered directly within villages by culturally competent
providers. We conducted a retrospective chart review of all 288 women who
initiated a contraceptive method over a 16-month period and conducted a logistic
regression to obtain adjusted odds ratios (OR) for predictors of LARC uptake.
RESULTS: Overall 79.2% of women elected a LARC method. More than half of women
(49.8%) switched to LARC from short-acting hormonal methods. In the univariate
analysis prior use of short-acting method (p = 0.014), number of prior methods (p
= 0.049), and current contraceptive use (p<0.01) were significantly associated
with choosing a LARC. In the logistic regression model current use of
contraception remained significant (OR 3.29, 95% CI 1.67-8.04). Report of
abnormal bleeding or other side effects from prior short-acting method use did
not predict LARC uptake (p = 0.82 and p = 0.079). CONCLUSIONS: Most women in this
marginalized population opted for a LARC method. IMPLICATIONS: Low utilization of
LARCs may be related to service delivery factors. Further research is needed to
validate these conclusions prospectively and in less selected populations.
PMID- 29949634
TI - Production pathways for CH4 and CO2 in sediments of two freshwater ecosystems in
south-eastern Poland.
AB - This paper presents the results of research into pathways leading to the
production of methane (CH4) and carbon dioxide (CO2) in sediments of two
eutrophic reservoirs (Maziarnia and Nielisz), located in south-eastern Poland. In
seeking to identify the pathways in question, use was made of analysis of stable
carbon isotopes in CH4 and CO2 dissolved in pore water. This determined that CH4
is mainly produced through acetate fermentation, though the hydrogenotrophic
methanogenic process may also be of importance, especially in deeper layers of
sediments. Both the presence of autochthonous organic matter and increased pH
values are shown to favour acetate fermentation. In turn, methanogenesis in
sediments is assessed as capable of accounting for the generation of a
considerable amount of CO2. Indeed, the role of methanogenesis in CO2 production
is increasingly important further down in the layers of sediment, where
allochthonous organic matter is predominant.
PMID- 29949635
TI - Development of a high-throughput assay to detect antibody inhibition of low pH
induced conformational changes of influenza virus hemagglutinin.
AB - Many broadly neutralizing antibodies (bnAbs) bind to conserved areas of the
hemagglutinin (HA) stalk region and can inhibit the low pH induced HA
conformational changes necessary for viral membrane fusion activity. We developed
and evaluated a high-throughput virus-free and cell-free ELISA based low pH
induced HA Conformational Change Inhibition Antibody Detection Assay (HCCIA) and
a complementary proteinase susceptibility assay. Human serum samples (n = 150)
were tested by HCCIA using H3 recombinant HA. Optical density (OD) ratios of mAb
HC31 at pH 4.8 to pH 7.0 ranged from 0.87 to 0.09. Our results demonstrated that
low pH induced HA conformational change inhibition antibodies (CCI) neutralized
multiple H3 strains after removal of head-binding antibodies. The results suggest
that HCCIA can be utilized to detect and characterize CCI in sera, that are
potentially broadly neutralizing, and serves as a useful tool for evaluating
universal vaccine candidates targeting the HA stalk.
PMID- 29949636
TI - The care, stimulation and nutrition of children from 0-2 in Malawi-Perspectives
from caregivers; "Who's holding the baby?"
AB - INTRODUCTION: Universal access to quality early childhood development and care is
a fundamental part of Sustainable Development Goal 4.2.1. Research from diverse
settings, including that in low and middle income countries, now demonstrates the
positive impact that interventions to promote play, stimulation, early
communication and responsiveness can have, not just on child development, but on
long term gains in education and economic growth. International agencies have
recently produced the Nurturing Care Framework for Early Child Development in
order to promote this and to encourage countries to move the focus from child
survival to child thrival. Research on the best methods of integration of these
programmes into present care practices, particularly in African settings is still
very limited. METHODS: We used qualitative methods to gain an understanding of
care practices (play, developmental stimulation, early communication and
responsive feeding) for children 0-2 years. We conducted 18 focus groups (FGDs),
six PFGDs (Participatory Research focus groups), 18 in depth interviews (IDIs)
and 20 observations with caregivers in rural and urban settings of Malawi. We
used a topic guide, audio-recorded the FGDs and IDIS and transcribed them in
Chichewa or Yao and then into English. We coded data using an inductive approach
to thematic analysis. We placed the data within a framework with the emerging
major and minor themes. We conducted quality assurance for translations and
coding frameworks through cross comparison of data and used respondent validation
to check our results. RESULTS: Malawian caregivers see children's play as a
consequence of good health and wellbeing, less an interaction that a parent
undertakes to promote wellbeing and learning. Non-verbal communication and
responsiveness with infants is clearly present and caregivers have many one-on
one interactions with young infants. Furthermore, many caregivers have good
knowledge of feeding recommendations but cannot always follow these due to
constraints on money. When children become mobile (toddlers), play is an activity
done more often between children or with other caregivers such as siblings or
grandparents. Community members consider that caring for children from 0-2 years
is a woman's domain. Despite this, both men and women acknowledge the importance
of maternal wellbeing in enabling good care of children. The present
socioeconomic situation of most families in our study means that income
generation and food security come first. Many mothers spend most of their time
managing the responsibilities of daily living and have limited time to dedicate
to children's play, responsiveness and communication with their children.
DISCUSSION: Programmes promoted as part of the Nurturing Care Framework which
provide advice on developmental stimulation, play, early communication and
responsive feeding should ensure that topics within these programmes are
culturally appropriate for the setting. Furthermore, programmes must not be an
added burden to parents but be supportive to parents managing many
responsibilities of daily living. Multi-sectorial approaches where both men and
women are provided with knowledge but are also supported through programmes which
address family finances, safe spaces for children whilst families are working,
and family mental health and relationships may enable programmes to work more
effectively.
PMID- 29949637
TI - Correction: Characterization of kidney CD45intCD11bintF4/80+MHCII+CX3CR1+Ly6C-
"intermediate mononuclear phagocytic cells".
AB - [This corrects the article DOI: 10.1371/journal.pone.0198608.].
PMID- 29949638
TI - Amplitude-modulated cold atmospheric pressure plasma jet for treatment of oral
candidiasis: In vivo study.
AB - The aim of this study was to establish an effective and safe protocol for in vivo
oral candidiasis treatment with atmospheric plasma jets. A novel amplitude
modulated cold atmospheric pressure plasma jet (AM-CAPPJ) device, operating with
Helium, was tested. In vitro assays with Candida albicans biofilms and Vero cells
were performed in order to determine the effective parameters with low
cytotoxicity. After the determination of such parameters, the protocol was
evaluated in experimentally induced oral candidiasis in mice. AM-CAPPJ could
significantly reduce the viability of C. albicans biofilms after 5 minutes of
plasma exposure when compared to the non-exposed group (p = 0.0033). After this
period of exposure, high viability of Vero cells was maintained (86.33 +/-
10.45%). Also, no late effects on these cells were observed after 24 and 48 hours
(83.24+/-15.23% and 88.96+/-18.65%, respectively). Histological analyses revealed
significantly lower occurrence of inflammatory alterations in the AM-CAPPJ group
when compared to non-treated and nystatin-treated groups (p < 0.0001). Although
no significant differences among the values of CFU/tongue were observed among the
non-treated group and the groups treated with AM-CAPPJ or nystatin (p = 0.3201),
histological analyses revealed marked reduction in candidal tissue invasion. In
conclusion, these results point out to a clinical applicability of this protocol,
due to the simultaneous anti-inflammatory and inhibitory effects of AM-CAPPJ with
low cytotoxicity.
PMID- 29949639
TI - Aggressive bodyguards are not always the best: Preferential interaction with more
aggressive ant species reduces reproductive success of plant bearing extrafloral
nectaries.
AB - Variation in partner species and frequency of interaction between species pairs
are potential drivers of the net outcome of generalized mutualisms. In ant-plant
mutualisms, the quality of defence provided by ants is related to ant
aggressiveness. Hence, we hypothesize that the performance of plants bearing
extrafloral nectaries will be higher when they interact more frequently with more
aggressive ant species. We estimated ant aggressiveness in the field by observing
their behaviour towards soil baits. Afterwards, we observed the frequency with
which individuals from these ant species visited plants through an entire
reproductive cycle. We measured the production and persistence of plants
reproductive structures through this period and the total seed production.
Increasing in the interaction frequency with highly aggressive ants reduced the
number of floral buds and seeds produced. Increased visitation frequency by less
aggressive ants increased the number of floral buds and seeds per branch. The
inverse relationship between ant aggressiveness and seed production may be
influenced by the costs imposed by different mutualistic partners. Thus, frequent
interaction with highly aggressive ants may lead to a higher accumulation of
costs through time, resulting in a negative net outcome for the plants. Our
results bring new evidence highlighting the importance to incorporate temporal
aspects in the study of mutualistic interactions. We suggests that the quality of
mutualistic partners must be understood as a function of its per-interaction
benefit and their cumulative costs to their partner over time, what puts in check
our current classification regarding partner quality in mutualistic systems.
PMID- 29949640
TI - Factors influencing the migration of Iranian healthcare professionals: A
qualitative study.
AB - BACKGROUND: The migration of healthcare specialists from developing countries has
increased in recent years. This has caused a rapid reduction in the access to and
quality of healthcare services in such countries. The aim of this study is to
evaluate the factors affecting the migration of specialist human resources in
Iran's healthcare system. METHODS: This is a qualitative study, which was carried
out through semi-structured interviews between 2015 and 2016. For sampling,
purposive sampling method with maximum variation sampling was used. Further, data
saturation was observed by conducting 21 interviews, and data analysis was
performed using the MAXQDA10 content analysis software. RESULTS: Factors
affecting the migration of specialists were classified into five key themes,
including structural, occupational, personal, socio-political and economic
factors. These themes consisted of 12 categories and 50 subcategories. The most
important factors affecting the migration of our study population were structural
issues, occupational problems, and personal concerns. CONCLUSION: Identification
of factors influencing migration is the first step to prevent the migration of
specialist human resources. Implementing the recommendations proposed in this
study would assist to prevent migration of medical professionals.
PMID- 29949641
TI - Quantifier comprehension is linked to linguistic rather than to numerical skills.
Evidence from children with Down syndrome and Williams syndrome.
AB - Comprehending natural language quantifiers (like many, all, or some) involves
linguistic and numerical abilities. However, the extent to which both factors
play a role is controversial. In order to determine the specific contributions of
linguistic and number skills in quantifier comprehension, we examined two groups
of participants that differ in their language abilities while their number skills
appear to be similar: Participants with Down syndrome (DS) and participants with
Williams syndrome (WS). Compared to rather poor linguistic skills of individuals
with DS, individuals with WS display relatively advanced language abilities.
Participants with WS also outperformed participants with DS in a quantifier
comprehension task while number knowledge did not differ between the two groups.
When compared to typically developing (TD) children of the same mental age,
participants with WS displayed similar levels regarding quantifier abilities, but
participants with DS performed worse than the control group. Language abilities
but not number skills also significantly predicted quantifier knowledge in a
linear regression analysis, stressing the importance of linguistic abilities for
quantifier comprehension. In addition to determining the skills that are relevant
for comprehending quantifiers, our findings provide the first demonstration of
how quantifiers are acquired by individuals with DS and WS, an issue not
investigated so far.
PMID- 29949643
TI - Degradation of phenol via ortho-pathway by Kocuria sp. strain TIBETAN4 isolated
from the soils around Qinghai Lake in China.
AB - Based on the feature of high-altitude permafrost topography and the diverse
microbial ecological communities of the Qinghai-Tibetan Plateau, soil samples
from thirteen different collection points around Qinghai lake were collected to
screen for extremophilic strains with the ability to degrade phenol, and one
bacterial strain recorded as TIBETAN4 that showed effective biodegradation of
phenol was isolated and identified. TIBETAN4 was closely related to Kocuria based
on its observed morphological, molecular and biochemical characteristics.
TIBETAN4 grew well in the LB medium at pH 7-9 and 0-4% NaCl showing
alkalophilicity and halophilism. The isolate could also tolerate up to 12.5 mM
phenol and could degrade 5 mM phenol within 3 days. It maintained a high phenol
degradation rate at pH 7-9 and 0-3% NaCl in MSM with 5 mM phenol added as the
sole carbon source. Moreover, TIBETAN4 could maintain efficient phenol
degradation activity in MSM supplemented with both phenol and glucose and complex
water environments, including co-culture Penicillium strains or selection of non
sterilized natural lake water as a culture. It was found that TIBETAN4 showed
enzymatic activity of phenol hydroxylase and catechol 1,2-dioxygenase after
induction by phenol and the corresponding genes of the two enzymes were detected
in the genome of the isolate, while catechol 2,3-dioxygenase or its gene was not,
which means there could be a degradation pathway of phenol through the ortho
pathway. The Q-PCR results showed that the transcripts of both the phenol
hydroxylase gene and catechol 1,2-dioxygenase gene were up-regulated under the
stimulation of phenol, demonstrating again that the strain degraded phenol via
ortho-degradation pathway.
PMID- 29949642
TI - Self-reported emotion regulation difficulties are associated with mood but not
with the biological stress response to thin ideal exposure.
AB - BACKGROUND: Difficulties in emotion regulation have been related to psychological
and physiological stress responses such as lower mood and lower parasympathetic
activation (HF-HRV) under resting condition, but evidence on the potential link
to the hypothalamic-pituitary-adrenal (HPA) axis functioning and to physiological
stress responses during a stress task is still scarce. The aim of the study was
to investigate stress responses in young women when confronted to a daily
stressor such as exposure to thin ideals and to understand the role of correlates
of self-reported trait-like emotion regulation difficulties (ERD). METHODS: Heart
rate variability (HRV) and salivary cortisol data were collected in a sample of
273 young women aged 18-35 with and without mental disorders during a vivid
imagination of thin ideals (experimental condition) or landscapes (control
condition). Changes in mood states were measured on a visual analogue scale (0
100). Correlates of trait-like ERD were self-reported using the Difficulties in
Emotion Regulation Scale (DERS). RESULTS: Participants with higher ERD showed a
stronger decline in self-reported mood after vivid imagination of thin ideals
compared to participants with lower ERD in the experimental condition but also a
stronger increase of positive mood with increasing ERD in the control condition.
ERD were not related to baseline HF-HRV or baseline salivary cortisol levels nor
to any physiological response during and after the imagination of thin ideals.
DISCUSSION AND CONCLUSION: The results corroborate the role of ERD regarding the
immediate psychological impact of daily stressors. Exposition to daily stressors
in the laboratory results in discrepant psychological and physiological
reactivity. Future studies should investigate under what conditions the complex
interrelations between immediate and long-term ERD and biological activation are
amenable to assessment in a laboratory setting. The additive effects of multiple
exposition to stressors, such as thin ideals in daily life, also need to be
addressed.
PMID- 29949644
TI - Timing of complementary feeding and associations with maternal and infant
characteristics: A Norwegian cross-sectional study.
AB - Norwegian Health authorities recommend solid food to be introduced between child
age 4-6 months, depending on both the mother's and infant's needs. The aim of
this paper is to describe timing of complementary feeding in a current sample of
Norwegian mother/infant-dyads and explore potential associations between timing
of introduction to solid foods and a wide range of maternal and infant
characteristics known from previous literature to influence early feeding
interactions. The paper is based on data from the Norwegian randomized controlled
trial Early Food for Future Health. In 2016, a total of 715 mothers completed a
web-based questionnaire at child age 5.5 months. We found that 5% of the infants
were introduced to solid food before 4 months of age, while 14% were not
introduced to solid food at 5.5 months of age. Introduction of solid food before
4 months of age was associated with the infant not being exclusive breastfed the
first month, receiving only formula milk at 3 months, the mother being younger,
not married/cohabitant, smoking, less educated and having more economic
difficulties. Not being introduced to solid food at 5.5 months was associated
with the infant being a girl, being exclusive breastfed the first month,
receiving only breastmilk at 3 months, the mother being older, married and having
3 or more children. This study shows that there are still clear socioeconomic
differences regarding timing of complementary feeding in Norway. Infants of
younger, less educated and smoking mothers are at higher risk of not being fed in
compliance with the official infant feeding recommendations. Our findings
emphasize the importance of targeting socioeconomically disadvantaged mothers for
support on healthy feeding practices focusing on the infant's needs to prevent
early onset of social inequalities in health.
PMID- 29949645
TI - The misery-is-not-miserly effect revisited: Replication despite opportunities for
compensatory consumption.
AB - Sadness increases how much decision makers pay to acquire goods, even when
decision makers are unaware of it. This effect is coined the "misery-is-not
miserly effect". The paper that first established this effect is the second most
cited article appearing in Psychological Science in 2004. In light of its impact,
the present study sought to assess whether the misery-is-not-miserly effect would
replicate (a) in a novel context and (b) even when another way of alleviating a
sense of loss (i.e., compensatory consumption) was available. Results revealed
that the effect replicated in the novel context and, despite a prediction
otherwise, even when individuals had an opportunity to engage in compensatory
consumption. Moreover, a meta-analysis of the original effect and that observed
in the present study yielded a small-to-medium effect (Cohen's d = 0.43). As
such, the present study lends evidentiary support to the misery-is-not-miserly
effect and provides impetus for future research exploring the impact of sadness
on consumer decision-making, specifically, and of emotion on decision processes,
more generally.
PMID- 29949646
TI - Gender difference in the relationship between the ferritin and homeostasis model
assessment of insulin resistance in non-diabetic Korean adults.
AB - BACKGROUND: The present study was conducted to assess gender difference in the
relationship between the ferritin and homeostasis model assessment of insulin
resistance (HOMA-IR) and beta cell function (HOMA-B) in non-diabetic Korean
adults. MATERIALS AND METHODS: A sample including 5,414 adults (2,279 men, 1,529
postmenopausal women, and 1,606 premenopausal women) aged >= 20 years from the
fifth Korean National Health and Nutrition Examination Survey (KNHANES V-1, 2010)
was analyzed. RESULTS: There were several key findings in the present study.
First, in men, HOMA-IR (beta = 0.119, 95% confidence interval [CI], 3.304 to
8.003) constituted the independent factor determining ferritin, but this was not
the case for HOMA-B (beta = -0.042, 95% CI, -0.100 to 0.011). Second, in
postmenopausal women, HOMA-IR (beta = 0.087, 95% CI, 0.899 to 5.238) was the
independent factor determining ferritin, but this was not the case for HOMA-B
(beta = -0.043, 95% CI, -0.065 to 0.010). Third, in premenopausal women, neither
HOMA-IR (beta = -0.050, 95% CI, -3.056 to 0.364) nor HOMA-B (beta = -0.009, 95%
CI, -0.028 to 0.020) constituted the independent factors determining ferritin.
CONCLUSIONS: Ferritin was positively associated with insulin resistance in non
diabetic Korean men and postmenopausal women, but not in non-diabetic Korean
premenopausal women.
PMID- 29949647
TI - From trust to skepticism: An in-depth analysis across age groups of adults with
sickle cell disease on their perspectives regarding hydroxyurea.
AB - Despite its efficacy, the uptake of HU in adults with sickle cell disease (SCD)
is poor likely due to a combination of system, provider, and patient-related
factors. We investigated attitudes of adult patients towards HU by conducting
qualitative interviews with 95 adult SCD patients (age 18 to 67 years old, 71
were female). While 53% of all participants reported that they were currently
taking HU, patients ranging in age 18-30 years (Group 1) were more likely to
report current HU use as compared to those (Group 2) ranging in age 31-67 years
(65% vs. 41% P = 0.01). Most Group 1 participants who reported currently taking
HU indicated that the decision to start HU was made by a parent, though some made
the decision themselves as a young adult. Group 1 participants expressed trust in
the efficacy of HU as well as trust that their physician adequately shared risks
and benefits for the medication. The Group 2 participants, who were not currently
on HU, were skeptical that all the risks and benefits of HU were known, were
concerned that the efficacy of HU was not proven, and that they were not
receiving complete information about its potential side effects. Of Group 2
participants who reported currently being on HU, 25% were concerned about the
side effects and efficacy of HU and reported continuing HU because of a lack of
effective alternatives. These data suggest that there are significant differences
by age in adult SCD patients' attitudes towards, utilization and understanding of
the risks and benefits of HU.
PMID- 29949648
TI - Who should receive treatment? An empirical enquiry into the relationship between
societal views and preferences concerning healthcare priority setting.
AB - INTRODUCTION: Policy makers increasingly need to prioritise between competing
health technologies or patient populations. When aiming to align allocation
decisions with societal preferences, knowledge and operationalisation of such
preferences is indispensable. This study examines the distribution of three views
on healthcare priority setting in the Netherlands, labelled "Equal right to
healthcare", "Limits to healthcare", and "Effective and efficient healthcare",
and their relationship with preferences in willingness to trade-off (WTT)
exercises. METHODS: A survey including four reimbursement scenarios was conducted
in a representative sample of the adult population in the Netherlands (n = 261).
Respondents were matched to one of the three views based on their agreement with
14 statements on principles for resource allocation. We tested for WTT
differences between respondents with different views and applied logit regression
models for examining the relationship between preferences and background
characteristics, including views. RESULTS: Nearly 65% of respondents held the
view "Equal right to healthcare", followed by "Limits to healthcare" (22.5%), and
"Effective and efficient healthcare" (7.1%). Most respondents (75.9%) expressed
WTT in at least one scenario and preferred gains in quality of life over life
expectancy, maximising gains over limiting inequality, treating children over
elderly, and those with adversity over those with an unhealthy lifestyle. Various
background characteristics, including the views, were associated with
respondents' preferences. CONCLUSIONS: Most respondents held an egalitarian view
on priority setting, yet the majority was willing to prioritise regardless of
their view. Societal views and preferences concerning healthcare priority setting
are related. However, respondents' views influence preferences differently in
different reimbursement scenarios. As societal views and preferences are
heterogeneous and may conflict, aligning allocation decisions with societal
preferences remains challenging and any decision may be expected to receive
opposition from some group in society.
PMID- 29949649
TI - Seamless assembly of recombinant adenoviral genomes from high-copy plasmids.
AB - The adenoviruses are essential tools for basic research and therapeutic
development. Robust methods for the generation of mutant and recombinant viruses
are crucial for these diverse applications. Here we describe a simple plasmid
based method that permits highly efficient modification of the adenoviral genome
and rapid production of high-titer virus stocks. The 36-kilobase genome of
adenovirus serotype 5 was divided into seven tractable blocks that could be
individually modified in a single step and reassembled in vitro. Because the
system is composed of compact modules, modifications at different loci can be
readily recombined. Viral assemblies were delivered to packaging cells by
electroporation, a strategy that consistently resulted in the de novo production
of 108 infectious units in 3-5 days. In principle, a similar strategy could be
applied to any other adenovirus serotype or to other double-strand DNA viruses.
PMID- 29949651
TI - 60th Annual Scientific Meeting American Headache Society.
PMID- 29949650
TI - Reconstructing diaphyseal tumors using radiated (50 Gy) autogenous tumor bone
graft.
AB - AIMS: Establish oncologic safety using 50 Gy to sterilize tumor bearing bone
before reimplantation in primary diaphyseal high grade extremity tumors,
determine extracorporeal radiotherapy (ECRT) graft survival, and analyze factors
that affect union at osteotomy sites. MATERIALS AND METHODS: Seventy non
metastatic patients underwent reconstruction with intercalary ECRT grafts
sterilized with 50 Gy. Diagnosis included osteosarcoma (38) and Ewing's sarcoma
(32). At last follow-up-49 patients were alive, 19 had died and 2 were lost to
follow up. Survivors had minimum follow up of 3 years (range 39-127 months).
RESULTS: Ninty one percent metaphyseal osteotomies united without additional
intervention compared to 71% diaphyseal osteotomies. Additional small plate at
diaphyseal osteotomy apparently reduced incidence of non-union (17% vs 31%) (P =
0.49). Addition of morsellised allograft did not help union. There were seven
(10%) local recurrences, all in soft tissue. Seventeen of 69 patients (25%)
needed removal of ECRT graft. Five year survival for ECRT graft (removal for all
causes) was 79% and 84% (excluding removal for local recurrence). CONCLUSIONS:
Reimplanting sterilized tumor bone using 50 Gy for tumor ablation is an easily
applicable, oncologically safe, biological reconstruction option for primary
diaphyseal extremity tumors.
PMID- 29949653
TI - Overwintering behavior of juvenile sea turtles at a temperate foraging ground.
PMID- 29949652
TI - FENS-Kavli winter symposium: Addressing the cellular phase of dementia-visions of
the UK Dementia Research Institute.
AB - This is a short report summarising the plenary talk by Professor Bart de
Strooper, at the 2017 FENS-Kavli winter symposium. We have tried to capture some
of the key points in his lecture on dementia research and we discuss his vision
for the new UK Dementia Research Institute (UK DRI). In his talk, Prof. de
Strooper encourages us to focus on the multicellular influence on brain
dysfunction in dementia and we summarise how the UK DRI is a timely and
ambitious, collaborative endevour, aiming to conquer dementia.
PMID- 29949654
TI - Adult soft tissue sarcoma and time to treatment initiation: An analysis of the
National Cancer Database.
AB - BACKGROUND: The primary goal of this investigation is to determine the current
national standards for time to treatment initiation (TTI) in soft tissue sarcoma
(STS). Additionally, we aim to identify the variables affecting TTI variability
in STS. METHODS: An analysis of the National Cancer Database identified 41 529
patients diagnosed with STS between 2004 and 2013. Kruskall-Wallis tests
identified differences between covariates regarding TTI. Negative binomial
regression models identified variables that independently influenced TTI, and
adjusted for confounders. RESULTS: The median TTI was 22.0 days and the mean TTI
was 29.7 days. Longer TTI was correlated with transitions in care between
institutions (Incidence rate ratio [IRR] = 1.76; P < 0.001), neoadjuvant
radiotherapy (IRR = 1.53; P < 0.001), neoadjuvant systemic therapy (IRR = 1.40; P
< 0.001), treatment at an academic center (IRR = 1.23; P < 0.001), Medicaid (IRR
= 1.18; P < 0.001), being uninsured (IRR = 1.13; P = 0.001), and Medicare (IRR =
1.05 P = 0.016) status. Shorter TTI was correlated with tumor size >5 cm (IRR =
0.93; P < 0.001), high grade (IRR = 0.92; P = 0.015), truncal tumor site (IRR =
0.94; P = 0.003), and median income >$63 000 (IRR = 0.95; P = 0.028).
CONCLUSIONS: The median TTI in the United States for STS is 22 days. Increased
TTI in STS are associated with tumor and treatment characteristics, socio
economic factors and hospital systems issues. Transitions in care between
institutions are responsible for the greatest increases.
PMID- 29949655
TI - Platelet-Derived TGF-beta Induces Tissue Factor Expression via the Smad3 Pathway
in Osteosarcoma Cells.
AB - Over the last three decades, the prognosis of osteosarcoma has remained
unchanged; the prognosis for patients with lung metastasis is still poor, and the
development of new treatments is urgently required. We previously showed that
aggressive osteosarcoma cells express more tissue factor (TF) and demonstrate
enhanced extrinsic pathway capacity. Furthermore, tumor growth can be suppressed
with the anticoagulant low molecular weight heparin. However, the molecular
mechanisms underlying TF regulation are still unclear. Here, we report that
transforming growth factor-beta (TGF-beta) upregulates TF, which can occur via
activated platelets. TF was found to be expressed on osteosarcoma cell surfaces,
which mediated the production of Xa and thrombin. TF induction by TGF-beta was
observed in several osteosarcoma cells, and especially in MG 63 cells. Both TF
expression by TGF-beta and extrinsic pathway activity through TF were rapidly
increased. This reaction was inhibited by a TGF-beta type I receptor inhibitor
and TGF-beta neutralizing antibody. Although TGF-beta was found to phosphorylate
both Smad2 and Smad3, their roles were markedly disparate. Surprisingly, Smad2
knockdown resulted in no inhibitory effect, whereas Smad3 knockdown completely
suppressed TGF-beta-induced TF expression. Next, data suggested that platelets
were the source of TGF-beta. We confirmed that thrombin-activated platelets and
osteosarcoma cells could release TGF-beta, and that platelet-derived TGF-beta
could induce TF expression. These processes were also inhibited by a TGF-beta
type I receptor inhibitor and Smad3 knockdown. Moreover, CD42b, TF, TGF-beta,
Smad2/3, and p-Smad2/3 were also detected in a biopsy sample from an osteosarcoma
patient. Collectively, these finding suggested that the interaction between
osteosarcoma cells and platelets, via thrombin and TGF-beta, results in a
continuous cycle, and that anti-platelet or anti-TGF-beta therapy could be a
promising tool for disease treatment. (c) 2018 American Society for Bone and
Mineral Research.
PMID- 29949656
TI - ORESARA15, a PLATZ transcription factor, mediates leaf growth and senescence in
Arabidopsis.
AB - Plant leaves undergo a series of developmental changes from leaf primordium
initiation through growth and maturation to senescence throughout their life
span. Although the mechanisms underlying leaf senescence have been intensively
elucidated, our knowledge of the interrelationship between early leaf development
and senescence is still fragmentary. We isolated the oresara15-1Dominant (ore15
1D) mutant, which had an extended leaf longevity and an enlarged leaf size, from
activation-tagged lines of Arabidopsis. Plasmid rescue identified that ORE15
encodes a PLANT A/T-RICH SEQUENCE- AND ZINC-BINDING PROTEIN family transcription
factor. Phenotypes of ore15-1D and ore15-2, a loss-of-function mutant, were
evaluated through physiological and anatomical analyses. Microarray, quantitative
reverse transcription polymerase chain reaction, and chromatin
immunoprecipitation as well as genetic analysis were employed to reveal the
molecular mechanism of ORE15 in the regulation of leaf growth and senescence.
ORE15 enhanced leaf growth by promoting the rate and duration of cell
proliferation in the earlier stage and suppressed leaf senescence in the later
stage by modulating the GROWTH-REGULATING FACTOR (GRF)/GRF-INTERACTING FACTOR
regulatory pathway. Our study highlighted a molecular conjunction through ORE15
between growth and senescence, which are two temporally separate developmental
processes during leaf life span.
PMID- 29949657
TI - Arbuscular mycorrhizal fungi: intraspecific diversity and pangenomes.
AB - Contents Summary 1129 I. Introduction 1129 II. Intraspecific phenotypic variation
and the plant host 1130 III. High inter-isolate genetic diversity in model AMF
1130 IV. Genome diversity within the model AM fungus Rhizophagus irregularis 1131
V. Pangenomes and the future of AMF ecological genomics 1131 Acknowledgements
1133 References 1133 SUMMARY: Arbuscular mycorrhizal fungi (AMF) are ubiquitous
plant symbionts with an intriguing population biology. Conspecific AMF strains
can vary substantially at the genetic and phenotypic levels, leading to direct
and quantifiable variation in plant growth. Recent studies have shown that high
intraspecific diversity is very common in AMF, and not only found in model
species. Studies have also revealed how the phenotype of conspecific isolates
varies depending on the plant host, highlighting the functional relevance of
intraspecific phenotypic plasticity for the AMF ecology and mycorrhizal
symbiosis. Recent work has also demonstrated that conspecific isolates of the
model AMF Rhizophagus irregularis harbor large and highly variable pangenomes,
highlighting the potential role of intraspecific genome diversity for the
ecological adaptation of these symbionts.
PMID- 29949658
TI - Multi-level analysis of alcohol-related injury, societal drinking pattern and
alcohol control policy: emergency department data from 28 countries.
AB - BACKGROUND AND AIMS: Societal-level volume and pattern of drinking and alcohol
control policy have received little attention in the alcohol and injury
literature. The aim of this study was to estimate the association between alcohol
related injury, individual-level drinking variables, country-level detrimental
drinking pattern and alcohol policy. DESIGN: Probability samples of emergency
department (ED) patients from the International Collaborative Alcohol and Injury
Study (ICAIS), which includes four collaborative ED studies on alcohol and
injury, all using a similar methodology, were analyzed with multi-level modeling
of individual-level drinking variables and aggregate-level variables (country
drinking pattern and alcohol policy) on alcohol-related injury in 33 ED studies.
SETTING: Sixty-two emergency departments in 28 countries covering five regions.
PARTICIPANTS: A total of 14 390 injured patients arriving to the ED within 6
hours following injury. MEASURES: Alcohol-related injuries (self-reported
drinking prior to the event and causal attribution of injury to drinking) were
analyzed in relation to individual-level volume and pattern of drinking, study
level alcohol volume, country detrimental drinking pattern (DDP) and an alcohol
policy measure, the International Alcohol Policy and Injury Index (IAPII). The
IAPII includes four regulatory domains: availability, vehicular, advertising and
drinking context. FINDINGS: Controlling for demographic characteristics,
individual-level drinking and study-level volume, the IAPII was associated
significantly with the proportion of both self-reported drinking [confidence
interval (CI) = 0.97-0.99; P < 0.001] and causal attribution (CI = 0.97-0.99; P <
0.01) and DDP had little effect on these associations. All four domains were
significantly predictive of self-reported drinking [availability (CI = 0.93-0.98,
P < 0.01); vehicular (CI = 0.91-0.97, P < 0.001); advertising CI = 0.82-0.94, P <
0.01); and context (CI = 0.93-0.99, P < 0.01], while only the vehicular domain
was significantly predictive of causal attribution (CI = 0.92-0.99; P < 0.05).
CONCLUSIONS: The more restrictive the alcohol policy in a country, the lower the
rate of alcohol-related injury, with country-level drinking pattern having little
effect on this relationship.
PMID- 29949659
TI - 1 H and 13 C NMR spectral assignments of 25 ethyl 2-oxocyclohex-3
enecarboxylates.
PMID- 29949660
TI - Elicitors and defense gene induction in plants with altered lignin compositions.
AB - A reduction in the lignin content in transgenic plants induces the ectopic
expression of defense genes, but the importance of altered lignin composition in
such phenomena remains unclear. Two Arabidopsis lines with similar lignin
contents, but strikingly different lignin compositions, exhibited different
quantitative and qualitative transcriptional responses. Plants with lignin
composed primarily of guaiacyl units overexpressed genes responsive to oomycete
and bacterial pathogen attack, whereas plants with lignin composed primarily of
syringyl units expressed a far greater number of defense genes, including some
associated with cis-jasmone-mediated responses to aphids; these plants exhibited
altered responsiveness to bacterial and aphid inoculation. Several of the defense
genes were differentially induced by water-soluble extracts from cell walls of
plants of the two lines. Glycome profiling, fractionation and enzymatic digestion
studies indicated that the different lignin compositions led to differential
extractability of a range of heterogeneous oligosaccharide epitopes, with
elicitor activity originating from different cell wall polymers. Alteration of
lignin composition affects interactions with plant cell wall matrix
polysaccharides to alter the sequestration of multiple latent defense signal
molecules with an impact on biotic stress responses.
PMID- 29949661
TI - Evolutionary diversification of CYC/TB1-like TCP homologs and their recruitment
for the control of branching and floral morphology in Papaveraceae (basal
eudicots).
AB - Angiosperms possess enormous morphological variation in plant architectures and
floral forms. Previous studies in Pentapetalae and monocots have demonstrated the
involvement of TCP domain CYCLOIDEA/TEOSINTE BRANCHED1-like (CYC/TB1) genes in
the control of floral symmetry and shoot branching. However, how TCP/CYC-like
(CYL) genes originated, evolved and functionally diversified remain unclear. We
conducted a comparative functional study in Ranunculales, the sister lineage to
all other eudicots, between Eschscholzia californica and Cysticapnos vesicaria,
two species of Papaveraceae with actinomorphic and zygomorphic flowers,
respectively. Phylogenetic analysis indicates that CYL genes in Papaveraceae form
two paralogous lineages, PapaCYL1 and PapaCYL2. Papaveraceae CYL genes show
highly diversified expression patterns as well as functions. Enhanced branching
by silencing of EscaCYL1 suggests that the role of CYC/TB1-like genes in
branching control is conserved in Papaveraceae. In contrast to the arrest of
stamen development in Pentapetalae, PapaCYL genes promote stamen initiation and
growth. In addition, we demonstrate that CyveCYLs are involved in perianth
development, specifying sepal and petal identity in Cysticapnos by regulating the
B-class floral organ identity genes. Our data also suggest the involvement of
CyveCYL genes in the regulation of flower symmetry in Cysticapnos. Our work
provides evidence of the importance of TCP/CYC-like genes in the promotion of
morphological diversity across angiosperms.
PMID- 29949662
TI - Broad spectrum developmental role of Brachypodium AUX1.
AB - Targeted cellular auxin distribution is required for morphogenesis and adaptive
responses of plant organs. In Arabidopsis thaliana (Arabidopsis), this involves
the prototypical auxin influx facilitator AUX1 and its LIKE-AUX1 (LAX) homologs,
which act partially redundantly in various developmental processes.
Interestingly, AUX1 and its homologs are not strictly essential for the
Arabidopsis life cycle. Indeed, aux1 lax1 lax2 lax3 quadruple knock-outs are
mostly viable and fertile, and strong phenotypes are only observed at low
penetrance. Here we investigated the Brachypodium distachyon (Brachypodium) AUX1
homolog BdAUX1 by genetic, cell biological and physiological analyses. We report
that BdAUX1 is essential for Brachypodium development. Bdaux1 loss-of-function
mutants are dwarfs with aberrant flower development, and consequently infertile.
Moreover, they display a counter-intuitive root phenotype. Although Bdaux1 roots
are agravitropic as expected, in contrast to Arabidopsis aux1 mutants they are
dramatically longer than wild type roots because of exaggerated cell elongation.
Interestingly, this correlates with higher free auxin content in Bdaux1 roots.
Consistently, their cell wall characteristics and transcriptome signature largely
phenocopy other Brachypodium mutants with increased root auxin content. Our
results imply fundamentally different wiring of auxin transport in Brachypodium
roots and reveal an essential role of BdAUX1 in a broad spectrum of developmental
processes, suggesting a central role for AUX1 in pooideae.
PMID- 29949664
TI - NR4A1 Regulates Motility of Osteoclast Precursors and Serves as Target for the
Modulation of Systemic Bone Turnover.
AB - NR4A1 (Nur77 or NGFI-B), an orphan member of the nuclear receptor superfamily,
has been identified as a key regulator of the differentiation and function of
myeloid, lymphoid, and mesenchymal cells. The detailed role of NR4A1 in bone
biology is incompletely understood. Here, we report a role for NR4A1 as novel
factor controlling the migration and recruitment of osteoclast precursors during
bone remodeling. Myeloid-specific but not osteoblast-specific deletion of NR4A1
resulted in osteopenia due to an increase in the number of bone-lining
osteoclasts. Although NR4A1-deficient osteoclast precursors displayed a regular
differentiation into mature osteoclasts, they showed a hyper-motile phenotype
that was largely dependent on increased osteopontin expression, suggesting that
expression of NR4A1 negatively controlled osteopontin-mediated recruitment of
osteoclast precursors to the trabecular bone. Pharmacological activation of
NR4A1, in turn, inhibited osteopontin expression and osteopontin-dependent
migration of osteoclast precursors resulted in reduced abundance of bone
resorbing osteoclasts in vivo as well as in an ameliorated bone loss after
ovariectomy in mice. This study identifies NR4A1 as a crucial player in the
regulation of osteoclast biology and bone remodeling and highlights this nuclear
receptor as a promising target for therapeutic intervention during the treatment
of osteoporosis. (c) 2018 The Authors. Journal of Bone and Mineral Research
Published by Wiley Periodicals Inc.
PMID- 29949663
TI - Frequency Dependent Tibial Neuromodulation of Bladder Underactivity and
Overactivity in Cats.
AB - OBJECTIVE: This study is aimed at determining if tibial nerve stimulation (TNS)
can modulate both bladder underactivity and overactivity. METHODS: In alpha
chloralose anesthetized cats, tripolar cuff electrodes were implanted on both
tibial nerves and TNS threshold (T) for inducing toe twitching was determined for
each nerve. Normal bladder activity was elicited by slow intravesical infusion of
saline; while bladder overactivity was induced by infusion of 0.25% acetic acid
to irritate the bladder. Bladder underactivity was induced during saline infusion
by repeated application (2-6 times) of 30-min TNS (5 Hz, 4-8T, 0.2 msec) to the
left tibial nerve, while TNS (1 Hz, 4T, 0.2 msec) was applied to the right tibial
nerve to reverse the bladder underactivity. RESULTS: Prolonged 5-Hz TNS induced
bladder underactivity by significantly increasing bladder capacity to 173.8% +/-
10.4% of control and reducing the contraction amplitude to 40.1% +/- 15.3% of
control, while 1 Hz TNS normalized the contraction amplitude and significantly
reduced the bladder capacity to 130%-140% of control. TNS at 1 Hz in normal
bladders did not change contraction amplitude and only slightly changed the
capacity, but in both normal and underactive bladders significantly increased
contraction duration. The effects of 1 Hz TNS did not persist following
stimulation. Under isovolumetric conditions when the bladder was underactive, TNS
(0.5-3 Hz; 1-4T) induced large amplitude and sustained bladder contractions. In
overactive bladders, TNS during cystometry inhibited bladder overactivity at 5 Hz
but not at 1 Hz. CONCLUSIONS: This study indicates that TNS at different
frequencies might be used to treat bladder underactivity and overactivity.
PMID- 29949665
TI - The Xanthomonas effector XopK harbours E3 ubiquitin-ligase activity that is
required for virulence.
AB - Xanthomonas oryzae pv. oryzae is the causative agent of rice bacterial leaf
blight. While the type III secretion system of X. oryzae pv. oryzae is essential
for virulence, the biochemical activities and virulence mechanisms of non
transcription activator-like (non-TAL) effectors delivered by this system are
largely unknown. Here, by screening for non-TAL effectors that contribute to X.
oryzae pv. oryzae virulence, we revealed that Xanthomonas outer protein K (XopK)
inhibits pathogen-associated molecular pattern-triggered immunity upstream of
mitogen-activated protein kinase cascades. Specifically, XopK interacted with and
directly ubiquitinated rice somatic embryogenic receptor kinase 2 (OsSERK2),
resulting in its degradation. Accordingly, mutation of a putative ubiquitin
conjugation enzyme (E2) binding site abolished XopK-induced degradation of
OsSERK2 and compromised XopK-dependent virulence. As crucial immune regulators
associated with a multitude of immune receptors, SERKs have been shown to be
perturbed by Pseudomonas effectors via different mechanisms. Our study revealed a
distinct perturbation mechanism of SERK activity via ubiquitination achieved by
Xanthomonas non-TAL effector.
PMID- 29949666
TI - The ypT category does not impact overall survival in node negative gastric
cancer.
AB - BACKGROUND: Although the eighth-edition American Joint Committee on Cancer (AJCC)
gastric cancer staging system created ypTNM staging for patients who underwent
preoperative therapy, the ideal ypTNM grouping is unknown. We sought to
investigate risk factors for OS in ypT0-3N0M0 gastric cancer. METHODS: From an
institutional database of The University of Texas MD Anderson Cancer Center and
the National Cancer Database (NCDB), we identified patients with ypT0-3N0M0
gastric adenocarcinoma who underwent R0 gastrectomy after chemotherapy or
chemoradiation during 1995-2015 (MD Anderson) or 2006-2014 (NCDB). RESULTS: The
study included 175 MD Anderson and 3200 NCDB patients. By multivariable analysis,
ypT category was not associated with OS (hazard ratio [HR] for ypT3 vs ypT1: MD
Anderson, 0.83 [95% CI, 0.36-1.92], P = 0.669; NCDB, 0.96 [95% CI, 0.85-1.08], P
= 0.472). cN-positive disease was not associated with OS in the MD Anderson
cohort (HR, 0.96 [95% CI, 0.55-1.67]; P = 0.873) but was weakly associated with
shorter OS in the NCDB cohort (HR, 1.11 [95% CI, 1.01-1.21]; P = 0.031).
CONCLUSIONS: The ypT category does not impact OS in ypT0-3N0M0 gastric cancer.
The impact of cN status on OS appeared limited. These findings should be
considered in future systems of post-neoadjuvant pathologic staging.
PMID- 29949667
TI - The association of length of hospital stay with readmission after elective
pancreatic resection.
AB - OBJECTIVE: The aim of this study was to identify if prolonged length of hospital
stay was protective for certain post-discharge complications requiring
readmission after pancreatectomy. METHODS: Patients undergoing elective
pancreatectomy from 2012 to 2013 were identified in the American College of
Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Multivariate
regression analyses were conducted to elucidate the association of length of
hospital stay (LOS), in-hospital complications, and post-discharge complications
with 30-day hospital readmission. RESULTS: Mean LOS for the readmitted versus not
readmitted cohort was 9.01 and 10.36, respectively (P < 0.001). Approximately
half of hospital readmissions occur within 7 days of discharge from the hospital.
The readmission rate (after hospital discharge) for patients with any in-hospital
complication was 13.2%. On the other hand, the readmission rate for patients with
any post-discharge complication was 70.8%. Readmission rates were above 85% for
patients with the following post-discharge complications: organ/space surgical
site infection (SSI), pneumonia, ventilator dependence greater than 48 h,
progressive renal insufficiency, sepsis, and septic shock. In a multivariate
logistic regression model, prolonged LOS reduced the odds of any post-discharge
complication requiring readmission (OR = 0.68, P = 0.01). Specifically, prolonged
LOS reduced the odds of a post-discharge organ/space SSI requiring readmission
(OR = 0.72, P = 0.02). CONCLUSION: Readmission after pancreatectomy primarily
occurs due to a new post-discharge event. Furthermore, increased LOS is
protective for readmission for post-pancreatectomy complications, particularly
those due to post-discharge organ space SSIs. Our findings suggest that solely
focusing on reducing LOS in pancreatectomy may lead to the unintended consequence
of increasing readmission rates.
PMID- 29949668
TI - Age-dependent prognostic value of body mass index for non-metastatic clear cell
renal cell carcinoma: A large multicenter retrospective analysis.
AB - BACKGROUND AND OBJECTIVES: The prognostic value of obesity is unestablished for
renal cell carcinoma. We assessed the age-dependent prognostic value of body mass
index (BMI) in a large multicenter cohort of patients with non-metastatic clear
cell renal cell carcinoma (nm-cRCC). METHODS: This study evaluated 2092 patients
with nm-cRCC who underwent surgery with curative intent at five Korean
institutions between 2001 and 2014. RESULTS: There was no significant difference
in BMI between the young (<45 years) and older patients (>=45 years) (P = 0.398).
Among older patients, high BMI (>=25 kg/m2 ) was associated with better 5-year
rates of recurrence-free survival (RFS) and cancer-specific survival (CSS) (P =
0.003 and 0.004, respectively), and multivariate analysis confirmed that high BMI
was independently associated with better RFS and CSS (RFS hazard ratio [HR]:
0.617, P = 0.005; CSS HR: 0.588, P = 0.024). However, among young patients, there
were no significant BMI-related differences in the 5-year RFS and CSS rates (P =
0.457 and 0.420, respectively), and high BMI was not independently associated
with RFS or CSS (P = 0.822 and 0.749, respectively). CONCLUSIONS: Among patients
with nm-cRCC, high BMI was associated with a favorable prognosis among older
patients but not among young patients. Therefore, the relationship between
obesity and nm-cRCC prognosis might vary according to age.
PMID- 29949669
TI - Nudge-nudge, WNK-WNK (kinases), say no more?
AB - Contents Summary 35 I Overview of animal and plant WNK kinases 35 II. Structure:
domains and topology 36 III. Phylogeny-evolutionary relationships 41 IV. Plant
WNK kinase distribution and regulation of WNK expression and activity 41 V.
Functions of WNK family members in physiology and development 41 VI. Say no more?
Still many questions to be answered 45 Acknowledgements 46 References 46 SUMMARY:
WITH NO LYSINE (WNK) kinases are serine/threonine kinases uniquely characterized
by an anomalous placement of a catalytic lysine, hence their moniker. In animals,
WNK protein kinases play critical roles in protein trafficking of components that
mediate renal ion transport processes and regulate osmoregulation of cell volume.
In plants, the WNK kinase gene family is larger and more diverse. Recent studies
revealed WNK kinase roles in orchestrating the trafficking of an ion channel, a
lipid kinase complex in animals, and a heterotrimeric G protein signaling
component in plants that is necessary for signal transduction. For this reason,
new attention is geared toward investigating the mechanisms adopted by WNK
kinases to nudge intracellular proteins to their destinations. In this review,
the functions of WNK kinases in protein trafficking are derived from what we have
learned from the model organism Arabidopsis thaliana. To place this new idea in
context, we provide the predicted WNK kinase structures, their predicted
expression patterns, a speculated evolutionary pathway, and the regulatory roles
of plant WNKs in transport processes and other physiologies. We brazenly predict
that the WNK kinases in both plants and animals will soon be recognized as a
nexus for trafficking-based signal transduction.
PMID- 29949670
TI - Factors affecting mental health nurses working with clients with first-episode
psychosis: A qualitative study.
AB - : WHAT IS KNOWN ABOUT THE SUBJECT?: First-episode psychosis (FEP) usually occurs
in adolescence, a time of great change and upheaval and the effect on the
sufferer and their family can be immense The nurse's role is to alleviate this
suffering, aid recovery and minimize the risk of relapse. They manage this
onerous task ideally through the therapeutic relationship, and use the skills of
assessment and risk identification in order to maximize patient outcomes. WHAT
DOES THE STUDY ADD TO EXISTING KNOWLEDGE?: The study adds knowledge about the
challenges that mental health nurses experience specifically in the presentation
of first-episode psychosis The findings of this study reinforce the idea that
pathways to care need to be clearly identified with a community-wide educational
led experience This study illuminates the fact that additional training and
formalized clinical supervision are necessary for mental health nurses to improve
quality of care and reduce stress levels, both of which lead to better clinical
outcomes. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental Health nurses should
engage with additional training, formalized clinical supervision and avail of
peer support in order to improve confidence, skills and quality of care. Dialogue
among mental healthcare colleagues is important not only about caring for people
presenting with a first-episode psychosis but in relation to the wider community
and family. This demonstrates the need for family-centred care within the mental
health profession. There should be more recognition of the social impact on the
individual during untreated psychosis with regard to isolation and withdrawal as
well as factors which also affect help-seeking behaviours. ABSTRACT: Introduction
Although there is much research on mental health nurses working with individuals
presenting with psychosis, there is a lack of knowledge about the factors that
impact the experience of nurses in the presentation specifically of first-time
psychosis. Aim This study aimed to explore the factors that impact on the
experience of mental health nurses working with individuals and their families
who present with a first-time psychosis. Method This qualitative study was
conducted through individual semi-structured interviews with eight mental health
nurses recruited from community mental health settings with a minimum of 2 years
post-qualification experience. Data were then subjected to a thematic content
analysis. Results This study identified the importance of therapeutic engagement,
as well as the need to have clear pathways to care and building capacity through
clinical supervision and training when working with this population. Implications
for practice Mental Health nurses should engage with additional training,
formalized clinical supervision and avail of peer support in order to improve
confidence, skills and quality of care, leading to better therapeutic engagement.
Pathways to care should be embedded within the wider community to ensure ease of
access for individuals and their families. There should be more recognition of
the social impact on the individual during untreated psychosis with regard to
isolation and withdrawal as well as factors which also affect help-seeking
behaviours.
PMID- 29949671
TI - Programmed cell death ligand-1 protein expression and CD274/PD-L1 gene
amplification in colorectal cancer: Implications for prognosis.
AB - Programmed cell death ligand-1 (PD-L1) detection assays have not been
standardized for patients with colorectal cancer, and the prognostic value of PD
L1 expression is unclear. We compared the PD-L1 expression patterns in colorectal
cancer samples using various immunohistochemical assays using 3 primary PD-L1
antibodies (assay 1, MIH1; assay 2, E1L3; and assay 3, 22C3) and investigated the
prognostic implication of PD-L1 expression using each. Additionally, PD-L1 gene
amplification was evaluated using FISH. The percentage scorings and positivity
rates of the 3 assays differed; the degrees of correlation and concordance
between assays 2 and 3 were relatively high, whereas assay 1 was an outlier.
Multivariate analyses indicated that PD-L1 positivity in tumor cells and its
negativity in tumor-infiltrating lymphocytes were independent predictors of
poorer overall and disease-free survival in patients with colorectal cancer. PD
L1 gene amplification was found in 2 patients (PD-L1/CEP ratio, 5.60 and 5.84,
respectively); both had strong PD-L1 expression according to
immunohistochemistry. Overall, our study showed that PD-L1 expression status in
tumor and immune cells is an independent prognostic factor in patients with
colorectal cancer. Standardizations of both PD-L1 detection using
immunohistochemistry and the cut-off for positivity are necessary. Finally, PD-L1
gene amplification was found in a small fraction of samples, suggesting the
possibility of an ancillary test for PD-L1 evaluation.
PMID- 29949672
TI - Changes in plasma membrane damage inducing cell death after treatment with near
infrared photoimmunotherapy.
AB - Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer phototherapy modality
using an antibody conjugated to a photosensitizer, IRDye700DX. When the conjugate
binds to the plasma membrane and is exposed to NIR light, NIR-PIT-treated cells
undergo swelling, and target-selective necrotic/immunogenic cell death is
induced. However, the cytotoxic mechanism of NIR-PIT has not been elucidated. In
order to understand the mechanism, it is important to elucidate how the damage to
the plasma membrane induced by NIR light irradiation changes over time. Thus, in
the present study, we investigated the changes in plasma membrane permeability
using ions and molecules of various sizes. Na+ flowed into cells immediately
after NIR light irradiation, even when the function of transporters or channels
was blocked. Subsequently, fluorescent molecules larger than Na+ entered the
cells, but the damage was not large enough for dextran to pass through at early
time points. To assess these phenomena quantitatively, membrane permeability was
estimated using radiolabeled ions and molecules: 111 InCl3 , 111 In-DTPA, and 3 H
H2 O, and comparable results were obtained. Although minute plasma membrane
perforations usually do not induce cell death, our results suggest that the
minute damage induced by NIR-PIT was irreversibly extended with time. In
conclusion, minute plasma membrane damage is a trigger for the increase in plasma
membrane permeability, cell swelling, and necrotic/immunogenic cell death in NIR
PIT. Our findings provide new insight into the cytotoxic mechanism of NIR-PIT.
PMID- 29949673
TI - Creating Zipper-Like van der Waals Gap Discontinuity in Low-Temperature-Processed
Nanostructured PbBi2n Te1+3n : Enhanced Phonon Scattering and Improved
Thermoelectric Performance.
AB - Nanoengineered materials can embody distinct atomic structures which deviate from
that of the bulk-grain counterpart and induce significantly modified electronic
structures and physical/chemical properties. The phonon structure and thermal
properties, which can also be potentially modulated by the modified atomic
structure in nanostructured materials, however, are seldom investigated. Employed
here is a mild approach to fabricate nanostructured PbBi2n Te1+3n using a
solution-synthesized PbTe-Bi2 Te3 nano-heterostructure as a precursor. The as
obtained monoliths have unprecedented atomic structure, differing from that of
the bulk counterpart, especially the zipper-like van der Waals gap discontinuity
and the random arrangement of septuple-quintuple layers. These structural motifs
break the lattice periodicity and coherence of phonon transport, leading to
ultralow thermal conductivity and excellent thermoelectric z T.
PMID- 29949676
TI - Characterization and Reshaping of a Large and Hydrophobic Nucleophile Pocket in
Lipases/Acyltransferases.
AB - Lipases/acyltransferases, such as CpLIP2 from Candida parapsilosis and CduLAc
from Candida dubliniensis, catalyze acyl transfer preferentially over hydrolysis
if a suitable nucleophile is present, even in a medium with a high thermodynamic
activity of water (aW ). These enzymes are related to CAL-A from Moesziomyces
antarcticus, which, in comparison, displays a lower acyl transfer ability. The 3D
structures of wild types and mutants of CAL-A, CpLIP2, and CduLAc revealed
differences in size and hydrophobicity of a large pocket located under the
catalytic triad. The kinetic behavior of site-directed mutants confirmed the role
of this pocket in competition between methanol and water as the nucleophile
acceptor for the deacylation step. The mutations provided a better understanding
of key structural determinants for variable levels of acyltransferase ability
observed and supported the existence of a complex network of nucleophile
interactions within the enzymes. The shape and size of the possible nucleophile
pocket identified also suggested that multiple binding sites could exist, which
supported the hypothesis of non-overlapping leaving and accepting nucleophile
binding sites.
PMID- 29949675
TI - Nickel-Catalyzed Amination of Silyloxyarenes through C-O Bond Activation.
AB - Silyloxyarenes were utilized as electrophilic coupling partners with amines in
the synthesis of aniline derivatives. A diverse range of amine substrates were
used, including cyclic or acyclic secondary amines, secondary anilines, and
sterically hindered primary anilines. Additionally, a range of sterically
hindered and unhindered primary aliphatic amines were employed, which have
previously been challenging with other classes of aryl ether electrophiles.
Orthogonal couplings of silyloxyarenes with aryl methyl ethers are illustrated,
where selectivity between the two C-O electrophiles is determined by ligand
control, thereby allowing complementary and selective late-stage diversification
of either electrophile. Finally, a sequential coupling displays the utility of
this amination method along with the reversal in intrinsic reactivity between
aryl methyl ethers and silyloxyarenes.
PMID- 29949674
TI - Transcriptional repression of human epidermal growth factor receptor 2 by ClC-3
Cl- /H+ transporter inhibition in human breast cancer cells.
AB - Recent studies have indicated that the intracellular concentration of chloride
ions (Cl- ) regulates gene expression in several types of cells and that Cl-
modulators positively or negatively regulate the PI3K/AKT/mammalian target of
rapamycin (mTOR) and signal transducer and activator of transcription (STAT)3
signaling pathways. We previously reported that the Ca2+ -activated Cl- channel
anoctamine (ANO)1 regulated human epidermal growth factor receptor 2 (HER2)
transcription in breast cancer YMB-1 cells. However, the mechanisms underlying
ANO1-regulated HER2 gene expression have not yet been elucidated. In the present
study, we showed the involvement of intracellular organelle ClC-3 Cl- /H+
transporter in HER2 transcription in breast cancer MDA-MB-453 cells. The siRNA
mediated inhibition of ClC-3, but not ANO1, markedly repressed HER2 transcription
in MDA-MB-453 cells. Subsequently, treatments with the AKT inhibitor AZD 5363 and
mTOR inhibitor everolimus significantly enhanced HER2 transcription in MDA-MB-453
cells, whereas that with the STAT3 inhibitor 5,15-diphenylporphyrin (5,15-DPP)
inhibited it. AKT and mTOR inhibitors also significantly enhanced HER2
transcription in YMB-1 cells. The siRNA-mediated inhibition of ClC-3 and ANO1
resulted in increased AKT phosphorylation and decreased STAT3 phosphorylation in
MDA-MB-453 and YMB-1 cells, respectively. The intracellular Cl- channel protein
CLIC1 was expressed in both cells; however, its siRNA-mediated inhibition did not
elicit the transcriptional repression of HER2. Collectively, our results
demonstrate that intracellular Cl- regulation by ANO1/ClC-3 participates in HER2
transcription, mediating the PI3K/AKT/mTOR and/or STAT3 signaling pathway(s) in
HER2-positive breast cancer cells, and support the potential of ANO1/ClC-3
blockers as therapeutic options for patients with resistance to anti-HER2
therapies.
PMID- 29949677
TI - Highly Efficient Cell-Penetrating Probes of Protein Arginine Deiminases for
Functional Proteomics.
AB - Protein arginine deiminases (PADs) have recently emerged at the forefront of drug
discovery programs for several human disorders. Despite this, a precise
understanding of their functional roles in human biology remains to be fully
elucidated. This report highlights a recent development of next-generation
activity-based PAD probes that are highly efficient, cell active, and
metabolically stable. This discovery should rapidly expedite functional
assignments of PAD biology in both normal and diseased cells, thereby leading to
the development of PAD-targeted therapeutics in the near future.
PMID- 29949678
TI - Reaction of CO2 with a Vanadium(II) Aryl Oxide: Synergistic Activation of CO2
/Oxo Groups towards H-Atom Radical Abstraction.
AB - Treatment of divalent (ONNO)V(TMEDA) (1; ONNO=[2,4-Me2 -2-(OH)C6 H2 CH2 ]2 N(CH2
)2 NMe2 ) with CO2 afforded [(ONNO)V]2 (MU-OH)(MU-formate) (2). Whereas the
bridging hydroxo and formate groups both originated from CO2 , the H atoms
present on the two residues were obtained through H-atom radical abstraction from
the solvent. DFT calculations revealed an initially linear CO2 bonding mode,
followed by deoxygenation, and highlighted a synergistic effect between the so
formed oxo group and an additional bridging CO2 residue in promoting radical
behavior.
PMID- 29949680
TI - Assessing motor skills to inform a Fetal Alcohol Spectrum Disorder diagnosis
focusing on persons older than 12 years: A systematic review of the literature.
AB - METHODS: A systematic review of current evidence using various electronic
databases was conducted. Studies were appraised using a recognised clinical
appraisal tool. RESULTS: Seven studies published between 1998 and 2014 met the
inclusion criteria. There is some evidence that difficulties with fine motor
skills, visual motor integration, and balance skills persist in people who have
been prenatally exposed to alcohol. Most studies did not focus on adolescent or
adult participants in isolation, making it difficult to generalise results.
Varied methodological designs made it difficult to compare studies as few used
common standardised assessments Conclusion: A review of functional difficulties
in each individual would be required to determine if a motor assessment is
warranted. Further research is required using assessments recommended in
diagnostic guidelines to determine the common motor difficulties seen in
adolescents and adults.
PMID- 29949681
TI - Meta-Analysis of Pregnancy Outcomes after Exposure to TNF-alpha Inhibitors During
Pregnancy for the Treatment of Arthritic Diseases.
AB - TITLE: Pregnancy Outcomes after Exposure to TNF-alpha Inhibitors During Pregnancy
for the Treatment of Arthritic Diseases: A Meta-Analysis Authors: Mirdamadi K,
Salinas T, Vali R, Papadimitripulous M, Piquette-Miller M Background: Auto-immune
arthritic diseases affect many women of child-bearing age. Tumor necrosis factor
(TNF)-alpha inhibitors are currently used for the treatment of various immune
mediated diseases during pregnancy. However, there has been no evaluation of
safety in the treatment of arthritic diseases during gestation. Objective: To
analyze the risk of adverse pregnancy and neonatal outcomes after treatment of
arthritic diseases with TNF-alpha inhibitors. Methods: Major databases
including Ovid MEDLINE, Embase, and Web of Science, were searched inclusive to
April 2016. Observational prospective cohort studies evaluating pregnancy
outcomes after exposure to TNF-alpha inhibitors for the treatment of arthritic
diseases during pregnancy were included. Data on pregnancy and neonatal outcomes
was extracted from all included studies. A meta-analysis was performed using
inverse-variance random effect with a 95% confidence interval (95%CI) and p<0.05.
Results: Eight prospective studies with comparison groups were included in
the meta-analysis. TNF-alpha inhibitors were associated with significantly higher
risks of low birth weight (odds ratio (OR), 1.43; 95%CI, 1.00-2.04) and
significantly lower rates of live birth (OR, 0.61; 95%CI, 0.38-0.98). However,
birth defects, therapeutic abortion, spontaneous abortion, and preterm birth were
not significantly different between the two groups. Conclusion: Treatment of
arthritic diseases with TNF-alpha inhibitors during pregnancy increases the risk
of lower birth weight and decreases the rate of live birth in this population.
While duration of treatment and gestational age at exposure may play a role in
these outcomes, evaluation of risk versus benefit is crucial in this patient
population. Key words: TNF-alpha inhibitors, pregnancy outcomes, arthritic
disease, meta-analysis.
PMID- 29949682
TI - Prescribing Competency of Medical Students: National Survey of Medical Education
Leaders.
AB - Introduction Evidence suggests that newly licensed physicians are not adequately
prepared to prescribe safely. There is currently no national pre-licensure
prescribing competency assessment required in North America. This study's purpose
was to survey Canadian medical school leaders for their interest in and perceived
need for a nationwide prescribing assessment for final year medical students.
Method In spring of 2015, surveys were disseminated online to medical education
leaders in all 17 Canadian medical schools. The survey included questions on
perceived prescribing competency in medical schools, and interest in integration
of a national assessment into medical school curricula and licensing. Results
372 (34.6 %) faculty from all 17 Canadian medical schools responded. 277 (74.5%)
respondents were residency directors, 33 (8.9%) vice deans of medical education
or equivalent, and 62 (16.7%) clerkship coordinators. Faculty judged 23.4% (SD
22.9%) of their own graduates' prescribing knowledge to be unsatisfactory and 131
(44.8%) felt obligated to provide close supervision to more than a third of their
new residents due to prescribing concerns. 239 (73.0%) believed that an
assessment process would improve their graduates' quality, 262 (80.4%) thought it
should be incorporated into their medical school curricula and 248 (76.0%) into
the national licensing process. Except in regards to close supervision due to
concerns, there were no significant differences between schools' responses.
Conclusions Amongst Canadian medical school leadership, there is a perceived
inadequacy in medical student prescribing competency as well as support for a
standardized prescribing competency assessment in curricula and licensing
processes.
PMID- 29949679
TI - Tetraploidy in cancer and its possible link to aging.
AB - Tetraploidy, a condition in which a cell has four homologous sets of chromosomes,
is often seen as a natural physiological condition but is also frequently seen in
pathophysiological conditions such as cancer. Tetraploidy facilitates chromosomal
instability (CIN), which is an elevated level of chromosomal loss and gain that
can cause production of a wide variety of aneuploid cells that carry structural
and numerical aberrations of chromosomes. The resultant genomic heterogeneity
supposedly expedites karyotypic evolution that confers oncogenic potential in
spite of the reduced cellular fitness caused by aneuploidy. Recent studies
suggest that tetraploidy might also be associated with aging; mice with mutations
in an intermediate filament protein have revealed that these tetraploidy-prone
mice exhibit tissue disorders associated with aging. Cellular senescence and its
accompanying senescence-associated secretory phenotype have now emerged as
critical factors that link tetraploidy and tetraploidy-induced CIN with cancer,
and possibly with aging. Here, we review recent findings about how tetraploidy is
related to cancer and possibly to aging, and discuss underlying mechanisms of the
relationship, as well as how we can exploit the properties of cells exhibiting
tetraploidy-induced CIN to control these pathological conditions.
PMID- 29949683
TI - Impact of Drug Exposure Definitions on Observed Associations in
Pharmacoepidemiology Research.
AB - BACKGROUND - A variety of methods are used to define exposure in
pharmacoepidemiologic studies. Although each method has known biases, the
relative effect of these biases on an observed association has not been fully
examined. OBJECTIVE - To explore the influence of different exposure definitions
on estimates, using the association between metformin and all-cause mortality as
a proto-typical model. METHODS - New users of oral anti-hyperglycemic drugs were
identified using administrative health databases from Alberta, Canada between
1998 and 2010. Drug exposure was described using definitions that are commonly
used in observational studies. All analyses included the same covariates of age,
gender, and a comorbidity score, and subjects not exposed to metformin served as
the reference group. The measure of association was assessed using a Cox
Proportional Hazards model for cohort studies and conditional logistic regression
for case-control studies. RESULTS - We identified 64,293 new oral anti
hyperglycemic drugs users; mean age 68.9 years, 33,131 (52%) males, and 24,745
(39%) deaths during a mean follow-up of 6 years. In adjusted models, the
association between metformin and mortality ranged from 0.23 (95% CI 0.22-0.25)
to 0.92 (95% CI 0.88-0.95) reduction. Most metformin exposure definitions,
however, provided estimates in the 0.6-0.8 reduction range, aligning with the
results of previous observational studies. CONCLUSIONS - The variety of exposure
definitions tested in this analysis produced a wide range of associations between
metformin and mortality risk. Therefore, pharmacoepidemiological studies should
implement sensitivity analyses including at least two exposure definitions to
provide more robust and potentially valid study estimates.
PMID- 29949684
TI - Reduced Out-of-Pocket Costs and Medication Adherence - A Population-Based Study.
AB - BACKGROUND: In 2007, a drug benefit plan for Seniors (SDP) was launched in
Saskatchewan, Canada. SDP capped out-of-pocket costs at $15 per prescription for
individuals aged 65 and older. OBJECTIVES: To quantify the impact of the SDP on
chronic medication adherence. Methods: A retrospective cohort study was
conducted for participants aged 65 or older who were eligible to the SPD,
controlled by a younger group aged 40 to 64 who were ineligible. Adherence was
measured over 365 days using medication possession ratio (MPR). MPRs were
compared between age groups, and between pre and post SDP-launch periods. The
odds ratio of optimal adherence (i.e., MPR>=80%) was estimated using logistic
regression models with generalized estimating equations (GEE). RESULTS: Between
2005 and 2009, 353,568 adherence observations were observed from 188,109 unique
patients. Comparing the post-SDP period vs before, the increase in the odds of
optimal medication adherence was significant (OR=1.08, 95% CI: 1.04 to 1.11) and
was stronger after excluding patients already receiving medication benefits from
other government programs (OR= 1.21, 95% CI: 1.16 to 1.26). The SDP was
associated with improved adherence among the subgroup of prevalent medication
users (OR=1.08, 95% CI: 1.04 to 1.12), but not incident users (OR=1.05, 95% CI:
0.98 to 1.13). CONCLUSION: Reducing out-of-pocket medication costs for seniors
was associated with small improvements in medication adherence across the
population.
PMID- 29949685
TI - Why We Need To Be Redundant Slowing down is key to avoiding errors in EMS.
PMID- 29949686
TI - Chance Favors Only the Prepared Mind Do your homework before you go public.
PMID- 29949687
TI - Chronic Disease Management for the Community Paramedic.
PMID- 29949688
TI - It's Time to Embrace Point-of-Care Ultrasound: POCUS is the next level of care
for our patients.
PMID- 29949689
TI - Anaphylaxis and its Treatment.
PMID- 29949691
TI - Fifty Years of Modern EMS: Looking Back at the Paper That Started It All:
Accidental Death and Disability still greatly influences EMS today.
AB - For the most part EMS, despite all of its challenges, has kept up with the needs
of its communities and adapted to its role as a de facto safety net. When the
white paper was written, treatment for the injured varied radically from the
state to state and city to city. While some may feel the white paper was not the
impetus for all the changes outlines, it's difficult to argue these changes would
have happened as quickly without such and influential document. We must keep its
findings in mind to stay at the forefront of prehospital advancements, as opposed
to reacting as a necessity of survival.
PMID- 29949690
TI - EnoughStuff: Inventory Management in EMS A lot of skill (and a little guessing)
goes into keeping the stocks you need.
PMID- 29949692
TI - Are We Missing Obstructed Airways in SCA? With an SGA and no scope, a foreign
body might go undetected.
PMID- 29949693
TI - A One-Two Punch: Double Sequential Defibrillation for Refractory Cardiac Arrest.
PMID- 29949694
TI - New Minnesota Protocol May Help Salvage Patients With Refractory VF/VT.
PMID- 29949695
TI - Dangerous Assumptions A well-managed scene with PD present-what got missed?.
PMID- 29949696
TI - NEUROPROTECTIVE PROPERTIES OF A NEW INHIBITOR OF NA+/H+ EXCHANGER (COMPOUND RU
1355) ON THE MODEL OF FOCAL ISCHEMIA IN RATS.
AB - Primary neuroprotective properties of new inhibitor of Na+/+ exchanger (compound
RU-1355) were established on the model of 60-min focal ischemia of the left
middle cerebral artery followed by 24-h reperfusion in rats. Compound RU-1355
significantly (by 34%) decreased neurological symptoms, reduced (1.67 times) the
growth of neuron-specific enolase level in serum, decreased (2.3 times) the size
of the necrotic zone, and reduced by 59% (p <0.05) the degree of cerebral edema
According to the results of morphometric, immunoassay, and neurological
assessments of brain damage, compound RU-1355 is superior on ave- rage by 43.5%
(p < 0.05) in comparison to selective NHE1 inhibitor zoniporide.
PMID- 29949697
TI - STUDYING THE PHYSICAL DEPENDENCE ON AND TOLERANCE TO THE ANTINOCICEPTIVE EFFECT
OF RU-1205 SUBSTANCE.
AB - We have studied the physical dependence on and tolerance to the analgesic
activity of compound RU-1205. It is established that this compound does not cause
side effects typical of morphine and butorphanol including the development of
withdrawal syndrome upon naloxone provocation and tolerance to analgesic activity
upon 14-day administration.
PMID- 29949698
TI - POST-ANESTHETIC REHABILITATION PERIODS AND ANESTHESIA DOSAGE FOR LAPAROSCOPIC
CHOLECYSTECTOMY: RELATIONSHIP TO THE TOTAL OXIDATIVE CAPACITY OF LIVER.
AB - Analysis of the results of pharmacological phenotyping using antipyrine test
prior to providing anesthesia for laparoscopic cholecystectomy showed that
trimeperidine (promedol) dosing with allowance for the total oxidative capacity
of liver and the patient mass allows the periods of post-anesthetic
rehabilitation to be controlled. Clear algorithm of trimeperidine dosing based on
established indices of the total oxidative capacity of liver and is yet nor
developed because of restricted sampling set. The obtained results show
expediency of using and studying antipyrine test as a simple, cheap, and
informative method of individual anesthesia dosing for increasing the adequacy of
general anesthesia.
PMID- 29949699
TI - NEUROPROTECTIVE ACTION OF PHENIBUT AND NEUROGLUTAM IN EXPERIMENTAL CEREBRAL
ISCHEMIA ON THE BACKGROUND OF ALTERED IMMUNOREACTIVITY.
AB - Cerebroprotective activity of phenyl derivatives of GABA (phenibut, 25 mg/kg) and
L-glutamic acid (neuroglutam, 26 mg/kg) in rats with cerebral ischemia was
studied on the background of intact and altered immunoreactivity. Tested
compounds were administered intraperitoneally for 7 days after two phase ligation
of common carotid arteries (second artery was ligated 3 days after ligation of
the first artery). Immunosuppression caused by cyclosporin (daily dose 5 mg/kg,
p.o., for 13 days) worsened brain ischemia outcome, as manifested by increased
mortality, more severe neurological marker score, increased levels of brain
damage markers (NSE and MBP) in the blood serum, decrease in muscle strength and
locomotor activity, and impairment of orientation and research activity as
compared to animals with brain ischemia and intact immunity. Activation of immune
system was caused by lipopolysaccharide (10 mg/kg, i.p., 7 injections every
second day). Upon activation of the immune system, brain ischemia produced lower
mortality, while the survived rats exhibited more favorable outcome of ischemia
than animals with suppression of immune system: lover neurological marker score,
lower blood serum NSE and MBP levels (-35% on average,p < 0.05), and much higher
level of performance in motor coordination, muscular strength, and locomotor
activity (+90% on average, p < 0.05). The state of immune system significantly
influenced the neuroprotective activity of drugs tested. Neuroglutam
administration produced positive effect both in animals with intact immunity and
on the background of altered immunoreactivity. However, most positive outcome
after neuroglutam administration in ischemic rats was observed in animals with
suppression of immune system, with significant increase in the cerebral blood
flow level (+56%), decrease in NSE and MBP blood serum levels (57 and 76%,
respectively) after 7-day treatment as compared to the control group. The
therapeutic potential of phenibut was somewhat lower than that of neuroglutam,
and it was more pronounced in rats with activated immune system, whereas the drug
effectiveness in rats with suppressed immune system was less pronounced.
PMID- 29949700
TI - ANTI-INFLAMMATORY ACTIVITY OF SODIUM SALT OF 4-(O-beta-D
GLUCOPYRANOSYLOXY)BENZOIC ACID.
AB - We have evaluated the anti-inflammatory activity of the sodium salt of 4-(O-beta
D-glucopyranosyloxy)benzoic acid in comparison to well-known nonsteroidal anti
inflammatory drugs (NSAIDs). Carrageenan suspension (1%, 0.1 mL) was injected
into subplantar region of the right hindpaw of rats (n = 12) pretreated (7 days
and 60 min before carrageenan injection) intragastrically with methyl ester of
4(beta-D-glucopyranosyloxy)benzoic acid (20 mg/kg), acetylsalicylic acid (20
mg/kg), 4-hydroxybenzoic acid (20 mg/kg), or vehicle (2 mL of purified water).
Paw edema volume was measured plethysmographically at 1, 2 and 4 h after
carrageenan injection. The results showed that intragastric administration of the
sodium salt of 4-(O-beta-D-glucopyranosyloxy)benzoic acid in a dose of 20 mg/kg
for 7 days decreased the intensity of experimental inflammation.
PMID- 29949701
TI - EFFECT OF 3-HYDROXYPYRIDINE AND SUCCINIC ACID DERIVATIVES ON BACTERIAL GROWTH IN
DISCONTINUOUS CULTURES.
AB - We have studied the effect of domestic derivatives of 3-hydroxypyridine and
succinic acid (emoxipine, reamberin, and mexidol) on proliferation of E. coli, S.
aureus and E. faecalis in discontinuous cultures (DCs) over a period of 1 or 24
h. It is established that the drugs studied exhibit a biphase effect on the
number of bacterial colony-forming units (CFUs) in DCs of E. coli and E.faecalis.
This effect is manifested by the initial 1.3 - 3.5-fold decrease in the number of
CFUs (after 1-h incubation with drugs) with subsequent return to the control
level or 1.8 - 8.8-fold increase over the control level (after 24-h incubation
with drugs). In DCs of S. aureus that were incubated with the drugs, we observed
1.1 - 1.95-fold increase in CFU number after I-h incubation and 1.8 - 2.4-fold
increase after 24-h incubation. On the whole, the results of our studies
demonstrated a positive effect of 3-hydroxypyridine and succinic acid derivatives
on bacterial growth in DC. These drugs stimulated increase in CFU number in DCs
of test bacterial strains even at concentrations as low as 10-9 -10-6. The well
known efficiency of 3-hydroxypyridine and succinic acid derivatives in treatment
of infectious pathology appears independent of their direct effect on bacterial
growth.
PMID- 29949702
TI - RNA INTERFERENCE: NEW APPROACH TO THE TREATMENT OF ALLERGIC ASTHMA (A REVIEW).
AB - Asthma is among the most common chronic disorders of airways, which affects both
children and adults. Asthma being a common disease among different segments of
population, it has a high mortality rate and, in the absence of appropriate care,
affects the quality of life and leads to economics losses. In a view of
continuing growth in the incidence of asthma, it is important to find relevant
biological targets for developing new approaches to astma therapy. Recent
advances in molecular immunology, genetics, and bioinformatics allowed genes
involved in the pathogenesis of asthma to be identified, which provided
prerequisites for the development of new types of drugs that can regulate the
activity of pathogenically significant genes. To date, a number of technologies
for sequence-specific gene regulation (ASO, ribozymes, DNAzymes, EGS, DNA-decoys,
U 1-adapters) are available, but RNA interference is the most promising approach
in both terms of efficacy and financial cost. This review focuses on the
generalization and analysis of experimental data regarding the use of RNA
interference technology for the treatment of astma.
PMID- 29949703
TI - Effect of quercetin on the expression of Bcl-2/Bax apoptotic proteins in
endometrial cells of lipopolysaccharide-induced-abortion.
AB - OBJECTIVE: To explore the effect of quercetin on the expressions of Bcl-2/Bax
apoptotic proteins inendometrial cells in mice with abortion induced by
lipopolysaccharide. METHODS: For in vivo experiment, twenty five Kunming mice
were randomly divided into five groupsat day 4 of pregnancy, with 5 mice per
group. The mice were treated with lipopolysaccharide (LPS)through tail vein
intravenous injection at day 4 of pregnancy, followed by different concentrations
ofquercetin by oral gavage consecutively at days 5 to 6 of pregnancy. On day 7 of
gestation, the mice weresacrificed and the histopathological changes of the
uterus tissues were observed. Immunohistochemicalstaining was applied to the
detection of Bcl-2/Bax apoptotic proteins in the endometrial cells. For in
vitroexperiment, the primary endometrial cells were cultured using a uterus
tissue mass culturing methodsampled at day 4.5 of pregnancy. The cells were
treated with LPS with or without different dosagesof quercetin, respectively, for
12 h after 80% confluence. The expression of Bcl-2/Bax apoptotic proteinswere
detected by western blotting. RESULTS: Both the in vivo and in vitro experiments
showed decreased expression of Bcl-2 and enhancedexpression of Bax after LPS
treatment, leading to a decreased Bcl-2/Bax ratio. The expression ofBcl-2
significantly increased while the expression of Bax was significantly elevated,
in the LPS plus quercetingroup compared to the LPS only group. CONCLUSION: These
results suggest that quercetin has protective effect by partially regulating the
expressionof Bcl-2/Bax proteins, which in turn inhibits endometrial cell
apoptosis and benefits the embryoimplantation.
PMID- 29949704
TI - Effect of Wuziyanzong pill on levels of sex hormones, and expressions of nuclear-
associated antigen Ki-67 and androgen receptor intestes of young rats.
AB - OBJECTIVE: To evaluate the effects of Wuziyanzong pill on the levels of serum
follicle stimulatinghormone (FSH), luteinizing hormone (LH), testosterone (T) and
the expressions of nuclear-associatedantigen Ki67 (Ki67), androgen receptor (AR)
in testes of young rats. METHODS: Sixteen 20-day-old Wistar male rats were
randomly divided into control and treatmentgroup (n = 8). Rats in treatment group
were administered Wuziyanzong pill by gavage; rats in controlgroup administered
the same volume of saline. After 10 days of treatment, the rats were killed,
andthen serum and testes were taken. The levels of FSH, LH and T were measured by
radioimmunoassay(RIA). The histology of seminiferous tubule was observed by
hematoxylin-eosin (HE) staining. Theexpression of Ki67 was detected by
immunohistochemical assay (IHC). The mRNA level of Ki67, AR and CK-18 was
detected with quantitative real-time polymerase chain reaction (Q-RT-PCR),
theprotein level of AR and CK-18 were tested by Western blot. RESULTS: Compared
with control group, T level in treatment group increased significantly (P <
0.05).HE staining showed that both leydig cells and germ cells increased in
treatment group. Expressions ofKi67 and AR became higher after treatment. There
were no changes in CK-18 expression. CONCLUSION: Wuziyanzong pill can up-regulate
AR level to promote germ cell proliferation and differentiationin young male
rats.
PMID- 29949705
TI - Recognition and management of pediatric thyroid emergencies in the emergency
department.
AB - The wide range and vague nature of clinical presentations of thyroid emergencies
make accurate and timely diagnosis challenging. Patients with a variety of
thyroid conditions present to the emergency department, and appropriate suspicion
can reduce unnecessary delay and expense in determining the correct diagnosis.
This issue reviews the current evidence for presentation, evaluation, and
treatment for emergencies of thyroid function and anatomy including
hypothyroidism, hyperthyroidism, thyroid nodules, and thyroid trauma.
Complications of thyroid dysfunction are also considered, as well as
recommendations for disposition and follow-up.
PMID- 29949706
TI - Influence of Sanao Tang on urine volume and expression of aquaporin 2 in rats
with respiratory function impairment induced by passivesmoking and
lipopolysaccharide.
AB - OBJECTIVE: To investigate the effect of Sanao Tang (SAT) on urine volume and the
expression of aquaporin-2 (AQP2) in rats with lung dysfunction induced by passive
smoking and lipopolysaccharide. METHODS: Totally 45 healthy Specific pathogen
Free Wistar Rats were randomized into 3 groups:normal control group, model group
and SAT group. A rat model of respiratory dysfunction induced byexposure to
cigarette smoking and lipopolysaccharide (LPS). Lavage of decoction of the
Chinese medicinewas performed for rats in the SAT group. Anires 2005 System was
used to analyze the pulmonaryfunction. Urine of rats was collected through
metabolism cage method. Enzyme-linked immunosorbentassay (ELISA) was used to
determine content of antidiuretic hormone (ADH), angiotensin II (AngII), atrial
natriuretic factor (ANP), endothelin 1 (ET-1), nitric oxide (NO) and
prostaglandin E2(PGE2) in serum, lung and kidney. The expression of AQP2 in rat
renal tissue was determined with real-time fluorescence quantitative PCR (RT
PCR). RESULTS: (a) In comparison with the normal control, It was found that
enforced vital capacity (FVC),1-second forced expiratory volume/forced vital
capacity% (FEV(1)/FVC%), 24 h urine volume content ofNO and PGE2 were decreased,
while AQP2mRNA level and content of ADH, Agn II, ANP and ET-1were increased in
the model group with statistical significance (P < 0.05). (b) In comparison with
themodel group, It was found that FVC, FEV(1), FEV(1)/FVC%, 24 h urine volume,
content of PGE2 and NOdecreased, while AQP2mRNA level, content of ANP, ADH and
Ang II decreased in the SAT group withstatistical significance (P < 0.05).
CONCLUSION: SAT might effectively regulate the urine volume in the modeled rats;
ADH, Ang II,ANP, ET-1, NO and PGE2 might play an important role in the regulation
on urine volume by lungs.This might be the mechanisms underpinning the function
of lung governing water passage in termsof the theory of Traditional Chinese
Medicine.
PMID- 29949707
TI - Emergency department management of dyspnea in the dying patient.
AB - Dyspnea is one of the most distressing symptoms experienced by dying patients,
and it is a common reason for such patients to seek care in the emergency
department. Many underlying disease states and acute illnesses cause shortness of
breath at the end of life, and management tends to be symptomatic rather than
diagnostic, particularly in those for whom comfort is the most important goal.
Opioids are the most effective and widely studied agents available for palliation
of dyspnea in this population, while adjuvant therapies such as oxygen,
noninvasive positive pressure ventilation, and hand-held fans may also be used.
Benzodiazepines may also be helpful in select patients. The early involvement of
palliative medicine specialists and/or hospice services for dying patients can
facilitate optimal symptom management and transitions of care.
PMID- 29949708
TI - Effect of Asiasari radix on osteoblastic differentiation of stem cells derived
from gingiva.
AB - OBJECTIVE: To examine the dose-dependent impact of Asiasari Radix (A. radix) on
the cell viability,differentiation and mineralization of stem cells derived from
gingiva. METHODS: Stem cells that were derived from gingiva were grown in the
presence of A. radix at finalconcentrations that ranged from 0.001 to 10 MUg/mL.
The morphology of the cells was viewed underan inverted microscope and the
analysis of cell proliferation was performed by using Cell CountingKit-8 (CCK-8)
on day 1. The alkaline phosphatase activity test was used to assess
differentiation andAlizarin red S staining was used to assess mineralization of
treated cells. RESULTS: The control group showed spindleshaped, fibroblast-like
morphology and the shapes of the cells in 0.001, 0.01, 0.1, 1 and 10 MUg/mL of A.
radix were similar to that of the control group atday 1. The cultures growing in
the presence of 0.001 MUg/mL of A. radix at day 1 showed an increasein the CCK-8
value (P < 0.05). Cultures growing in the presence of 0.001 MUg/mL of A. radix
presentedthe highest value for alkaline phosphatase activity (P > 0.05).
Mineralized extracellular depositswere observed after Alizarin Red S staining and
the cultures grown in the presence of 0.001 MUg/mLof A. radix showed the highest
value for quantitative results for bound dye (P < 0.05). CONCLUSION: Within the
limits of this study, A. radix influenced the proliferation of stem cells
derivedfrom the gingiva and low concentrations of A. radix might enhance
osteogenic differentiation of the stem cells.
PMID- 29949709
TI - Effect of ethanol extract of HPRS, a Traditional Chinese Medicine formula, on
HCT116 cell Line.
AB - OBJECTIVE: In this study, we investigated the effects of ethanol extract of
Hupiruisu Fang (HPRS), aformula of Traditional Chinese Medicine, on HCT116 cell
line. METHODS: MKN45, A549, Hela and HCT116 cells were treated with ethanol
extract of HPRS alone orthe extract plus 5-Fluorouracil (5-FU) for 48 h, and then
the cell viabilities were measured using CCK-8Kit. The early apoptosis rate and
total apoptosis rate in both HCT116 cells were evaluated by flowcytometry. The
mRNA levels of apoptosis-related genes including caspase-3, caspase-8, Bcl2 and
Bax were detected by real-time quantitative polymerase chain reaction. Lastly,
the protein activitiesand expressions of those apoptosis related genes were
observed for further verifying the pro-apoptosisof the extract of HPRS. RESULTS:
Ethanol extract of HPRS could significantly induce apoptosis in HCT116 cell line.
Synergisticanalysis revealed that the extract exhibited a significant effect upon
5-FU-associated cytotoxicity in thecell line. CONCLUSION: The ethanol extract of
HPRS plus 5-FU might have the potential to improve the treatment of colorectal
cancer.
PMID- 29949710
TI - Effect on glycemia in rats with type 2 diabetes induced by streptozotocin: low
frequency electro-pulse needling stimulated Weiwanxiashu(EX-B 3) and Zusanli (ST
36).
AB - OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture
(EA) on bloodglucose in rats with streptozotocin-induced type 2 diabetes, and the
possible mechanism underlying the action. METHODS: Rat models were established
with high fat feeding and intraperitoneal injection ofstreptozotocin (STZ) (30
mg/kg). Rats with a random blood glucose > 16.7 mmol/L and blood glucoseat 2 h
point of oral glucose tolerance test (OGTT) > 11.1 mmol/L were included as
diabeticrats, and randomly divided into model group, EA Weiwanxiashu (EX-B 3)
group, EA Zusanli (ST 36)group, glimepiride group, and EA non-acupoint group (n =
12). EA (2 Hz continuous wave, 2 mA,20 min/day, 6 days/week, 4 weeks) and intra
gastric administration of glimepiride were applied asinterventions. With fasting
blood glucose and OGTT tested at the end of the intervention, the study observed
the patterns of hypoglycemic effects. For mechanism study, it observes
hematoxylinand eosin staining and Masson staining of pancreas paraffin sections,
protein expression of glucagon-like peptide 1 receptor (GLP-1R) in the pancreas
and skeletal muscle, glucose transporter 4(GLUT4) protein expression in skeletal
muscle membrane, to detect whether EA controls blood glucosevia regulation of GLP
1R. RESULTS: EA Weiwanxiashu (EX-B 3) significantly increased model rats'
pancreas GLP-1R, and GLUT4 ofskeletal muscle membrane; the therapy significantly
decreased model rats' skeletal muscle GLP-1R, restoredpancreas morphology, and
reduced fasting blood glucose and insulin resistance indices. CONCLUSION: EA
Weiwanxiashu (EX-B 3) alone has significant effect on glycemia. EA
Weiwanxiashu(EX-B 3) plus glimepiride further strengthen the effect. The
regulation of the GLP-1R in pancreas andskeletal muscle might be mechanism
underpinning the effect.
PMID- 29949711
TI - Effects of electronically stimulating Tianshu (ST 25) and Dachangshu (BL 25),
Quchi (LI 11) and Shangjuxu (ST 37) on the expressionsof jejunum c-kit protein
and c-kit mRNA in rats with functional diarrhea.
AB - OBJECTIVE: To investigate the effects of electronically stimulating Tianshu (ST
25) and Dachangshu(BL 25), Quchi (LI 11) and Shangjuxu (ST 37) on the jejunum c
kit protein and c-kit mRNA in rats withfunctional diarrhea (FD). METHODS: FD
models were established through intragastric administration with folium sennae.
Experimentalrats were then divided into 4 groups: blank group, model group,
electroacupuncturegroup I [Tianshu (ST 25) and Dachangshu (BL 25) of both sides]
and electroacupuncturegroup II [Quchi (Li 11) and Shangjuxu (ST 37) of both
sides], 10 in each. After treatment with electroacupuncture for 10 days, The
expressions of jejunum c-kit protein and c-kit mRNA in each groupwere detected
with Western blot and Real-Time quantitative real-time polymerase chain reaction
(PCR). RESULTS: The expressions of c-kit protein and c-kit mRNA in the model
group increased significantlycompared to those in the blank group (P < 0.01); the
expressions in electroacupuncture group Isignificantlydecreased compared to those
in the model group (P < 0.01). CONCLUSION: Our findings suggest that
electronicall stimulating both Tianshu (ST 25) andDachangshu (BL 25)
significantly increased the expressions of jejunum c-kit protein and c-kitmRNA in
FD rats, which means the treatment might have better therapeutic effects on FD.
PMID- 29949712
TI - Effect of combined medicated thread moxibustion plus needle picking therapy of
Zhuang nationality medicine on antioxidant levels ina rat model of sciatica.
AB - OBJECTIVE: To investigate the effect and underlying mechanisms of combined
medicated threadmoxibustion therapy plus needle picking therapy of Zhuang
nationality medicine on antioxidant levelsin a rat model of sciatica. METHODS:
One hundred Wistar rats, of specific pathogen free level, were randomly divided
intofive groups: normal control group, model group, medicated thread moxibustion
group, needle pickinggroup, and combination group. Each group contained 20 rats.
In the model, medicated thread moxibustion,needle picking, and combination
groups, sciatica models were established through chronic constriction injury of
the sciatic nerve. After the model was established, the rats in the
medicatedthread moxibustion, needle picking, and combination groups were given
the corresponding therapiesfor 21 days. The control and model groups received no
treatment. Reactive oxygen species, superoxidedismutase, malondialdehyde, and
total antioxidant capacity changes were determined.Nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase subunit NADPH oxidases 4(NOX4) mRNA
expression and the morphology of cells were observed to detect apoptosis of gamma
aminobutyric acid ergic (GABAergic) neurons. RESULTS: Compared with control
group, reactive oxygen species and malondialdehyde levels rosesignificantly in
the model group (P < 0.01), while superoxide dismutase and total antioxidant
capacitylevels were lowered (P < 0.05). Compared with the model group, reactive
oxygen species and malondialdehyde decreased in the needle picking group (P <
0.05), while superoxide dismutase levels wereincreased (P < 0.05); reactive
oxygen species and malondialdehyde significantly decreased in thecombination
group (P < 0.01). In addition, the model group had higher NOX4 mRNA expression
thanthat of the control group (P < 0.05), and the combination group had lower
expression levels than thatof the model group (P < 0.05). Apoptosis of GABAergic
neurons was observed in the model group, andwas attenuated after combined
therapy. CONCLUSION: The medicated thread moxibustion therapy plus needle picking
therapy of Zhuang nationalitymedicine can prevent oxidative damage in the rat
model of sciatica via down-regulating NOX4expression, improving antioxidant
capacity, and inhibiting the oxidative damage pathway of GABAergic neurons.
PMID- 29949713
TI - Silver Toxicity Thresholds for Multiple Soil Microbial Biomarkers.
AB - Material flow analysis shows that soil is a key repository for silver (Ag) from
(nano)silver-functionalized consumer products, but the potential effects of Ag
toxicity, via Ag+ release, on soil microbial communities and their ecosystem
services remains largely unknown. We examined the responses of multiple microbial
biomarkers to increasing Ag+ doses (nine concentrations, 0-2000 mg kg-1) in nine
different soils representing a wide range of soil properties. Analyses included
substrate-induced microbial respiration, nine different soil enzyme activities,
and quantification of bacterial 16S-rRNA (SSU) and fungal intergenic spacer (ITS)
copies. The resulting half-maximal effective concentrations (EC50) for Ag ranged
from ~1 to >500 mg kg -1 and showed soil-specific responses, including some
hormesis-type responses. Carbon cycle-associated enzyme activities (e.g.,
cellobiohydrolase, xylosidase, and alpha/beta-glucosidase) responded similarly to
Ag. Sulfatase and leucine-aminopeptidase activities (linked to the sulfur and
nitrogen cycles) were the most sensitive to Ag. Total organic carbon, and to a
lesser extent pH, were identified as potentially useful response predictors, but
only for some biomarkers; this reflects the complexity of soil Ag chemistry. Our
results show Ag toxicity is highly dependent on soil characteristics and the
specific microbial parameter under investigation, but end point redundancies also
indicated that representative parameters for key microbial functions can be
identified for risk assessment purposes. Sulfatase activity may be an important
Ag toxicity biomarker; its response was highly sensitive and not correlated with
that of other biomarkers.
PMID- 29949714
TI - Controlling Disorder by Electric-Field-Directed Reconfiguration of Nanowires To
Tune Random Lasing.
AB - Top-down fabrication is commonly used to provide positioning control of optical
structures; yet, it places stringent limitations on component materials, and
oftentimes, dynamic reconfigurability is challenging to realize. Here, we present
a reconfigurable nanoparticle platform that can integrate heterogeneous particle
assembly of different shapes, sizes, and chemical compositions. We demonstrate
dynamic control of disorder in this platform and use it to tune random laser
emission characteristics for a suspension of titanium dioxide nanowires in a dye
solution. Using an alternating current electric field, we control the nanowire
orientation to dynamically engineer the collective scattering of the sample. Our
theoretical model indicates that a change of up to 22% in scattering coefficient
can be achieved for the experimentally determined nanowire length distribution
upon alignment. Dependence of light confinement on anisotropic particle alignment
provides a means to reversibly tune random laser characteristics; a nearly 20
fold increase in lasing intensity was observed with aligned particle orientation.
We illustrate the generality of the approach by demonstrating enhanced lasing for
aligned nanowires of other materials including gold, mixed gold/dielectric, and
vanadium oxide.
PMID- 29949715
TI - Remarkable Acid Catalysis in Proton-Coupled Electron-Transfer Reactions of a
Chromium(III)-Superoxo Complex.
AB - Much enhanced acid catalysis was observed in oxygen atom transfer (OAT) reactions
by a mononuclear nonheme Cr(III)-superoxo complex, [(Cl)(TMC)CrIII(O2)]+ (1), in
the presence of triflic acid. In the acid-catalyzed reactions, the reactivity of
1 in OAT of thioanisole was enhanced significantly, showing more than 104-fold
acceleration in rate. Electron transfer (ET) from electron donors to 1 also
occurred only in the presence of HOTf. The enhanced reactivity of 1 by HOTf was
explained by proton-coupled electron transfer from electron donors, such as
ferrocene, to 1 in light of the Marcus theory of ET. The present study reports
for the first time the dramatic proton effect on the chemical properties of metal
superoxo species.
PMID- 29949716
TI - Multigenerational Attainments, Race, and Mortality Risk among Silent Generation
Women.
AB - This study extends health disparities research by examining racial differences in
the relationships between multigenerational attainments and mortality risk among
"Silent Generation" women. An emerging literature suggests that the socioeconomic
attainments of adjacent generations, one's parents and adult children, provide an
array of life-extending resources in old age. Prior research, however, has
demonstrated neither how multigenerational resources are implicated in women's
longevity nor how racial disparities faced by Silent Generation women may
differentially structure the relationships between socioeconomic attainments and
mortality. With data from the National Longitudinal Survey of Mature Women, the
analysis provided evidence of a three-generation model in which parent
occupation, family wealth, and adult child education were independently
associated with women's mortality. Although we found evidence of racial
differences in the associations between parental, personal, and spousal education
and mortality risk, the education of adult children was a robust predictor of
survival for black and white women.
PMID- 29949717
TI - Childhood Family Instability and Young Adult Health.
AB - American children live in a variety of family structures throughout their
childhoods. Such instability in family arrangements is common and has important
demonstrated implications for short-term child outcomes. However, it is not known
whether family instability experienced in childhood has enduring health
consequences across the life course. Using demographic, social, and biological
data from the National Longitudinal Study of Adolescent to Adult Health, we
investigate the family stress model, testing the relationship between parental
family instability in childhood and four biological markers of health in young
adulthood. This is the first study to examine whether the accumulation of family
change in childhood leaves a lasting physiological residue. While family
instability is associated with poorer short-term behavioral and socioeconomic
outcomes as documented in previous research, we find no evidence of deleterious
young adult health consequences. These findings are robust across different
measures of physiological health risk and types of family transitions.
PMID- 29949719
TI - Effect of a one-off sporidesmin challenge on the milk production of dairy cows.
AB - AIMS To investigate the effects on milk yield in lactating dairy cows of a single
dose of sporidesmin, and to categorise the responses based on clinical signs and
differing degrees of liver damage, as assessed by activities of gamma-glutamyl
transferase (GGT) and post-mortem liver histopathology. METHODS Adult lactating
dairy cows (n=17) were given a single intra-ruminal dose of 0.24 mg/kg of
sporidesmin dissolved in ethanol and diluted in water on Day 0; an additional
three cows served as untreated controls. Weekly serum samples were collected
between Days -14 and 42 and analysed for activities of GGT. Milk yields were
measured daily over the same period. Cows were subjected to euthanasia due to
severe clinical signs (n=2) or were slaughtered at the end of the trial. Samples
of livers were examined histologically and were scored for lesions on a scale
from 0 (normal) to 3 (severe). Based on GGT activities and clinical observations,
cows that were treated with sporidesmin were categorised as non-responders (no
clinical signs and normal GGT), subclinical (elevated GGT and no clinical signs)
or clinical. Outcomes were compared between these three groups and control cows
using generalised additive models. RESULTS Seven cows were classified as
clinical, and had median liver scores of 22 (95% CI=20.6-23.4), six were
subclinical with median liver scores of 8.7 (95% CI=3.8-13.5) and four were non
responders with median liver scores of 2.5 (95% CI=1.2-4.3). Median liver scores
for the three control cows were 1 (95% CI=-0.8-2.1). Activities of GGT increased
in subclinical and clinical cows around Day 7. The milk yield of all cows treated
with sporidesmin, including non-responder cows, started to decrease on Day 1, and
reached a nadir (a drop of between 9 and 85%) on Day 7. CONCLUSIONS AND CLINICAL
RELEVANCE It is likely that the overall effects of sporidesmin consumption on
milk production by the national herd in New Zealand are hugely underestimated,
especially considering its effects on non-responder and subclinical cows as shown
in this trial. In view of the results presented here, the authors are suggesting
a change to the definition of response to sporidesmin from non-responder,
subclinical, and clinical, to subclinical-low, subclinical-high, and clinical,
when measuring a combination of GGT activities, clinical signs and milk yields
during facial eczema-risk seasons (summer-autumn).
PMID- 29949718
TI - Whole-Genome Sequencing in Severe Chronic Obstructive Pulmonary Disease.
AB - Genome-wide association studies have identified common variants associated with
chronic obstructive pulmonary disease (COPD). Whole-genome sequencing (WGS)
offers comprehensive coverage of the entire genome, as compared with genotyping
arrays or exome sequencing. We hypothesized that WGS in subjects with severe COPD
and smoking control subjects with normal pulmonary function would allow us to
identify novel genetic determinants of COPD. We sequenced 821 patients with
severe COPD and 973 control subjects from the COPDGene and Boston Early-Onset
COPD studies, including both non-Hispanic white and African American individuals.
We performed single-variant and grouped-variant analyses, and in addition, we
assessed the overlap of variants between sequencing- and array-based imputation.
Our most significantly associated variant was in a known region near HHIP
(combined P = 1.6 * 10-9); additional variants approaching genome-wide
significance included previously described regions in CHRNA5, TNS1, and
SERPINA6/SERPINA1 (the latter in African American individuals). None of our
associations were clearly driven by rare variants, and we found minimal evidence
of replication of genes identified by previously reported smaller sequencing
studies. With WGS, we identified more than 20 million new variants, not seen with
imputation, including more than 10,000 of potential importance in previously
identified COPD genome-wide association study regions. WGS in severe COPD
identifies a large number of potentially important functional variants, with the
strongest associations being in known COPD risk loci, including HHIP and
SERPINA1. Larger sample sizes will be needed to identify associated variants in
novel regions of the genome.
PMID- 29949721
TI - Structural, Functional, and Genomic Diversity of Plant NLR Proteins: An Evolved
Resource for Rational Engineering of Plant Immunity.
AB - Plants employ a diverse intracellular system of NLR (nucleotide binding-leucine
rich repeat) innate immune receptors to detect pathogens of all types. These
receptors represent valuable agronomic traits that plant breeders rely on to
maximize yield in the face of devastating pathogens. Despite their importance,
the mechanistic underpinnings of NLR-based disease resistance remain obscure. The
rapidly increasing numbers of plant genomes are revealing a diverse array of NLR
type immune receptors. In parallel, mechanistic studies are describing diverse
functions for NLR immune receptors. In this review, we intend to broadly describe
how the structural, functional, and genomic diversity of plant immune receptors
can provide a valuable resource for rational engineering of plant immunity.
PMID- 29949720
TI - Development of a model for investigation of perennial ryegrass toxicosis in
sheep.
AB - AIMS To develop a clinical model of perennial ryegrass toxicosis (PRGT) based on
feeding a known dose of lolitrem B and ergotamine, and to produce a consistent
clinical presentation for assessment of disease pathophysiology, neurological
changes and neurohistopathology. METHODS Male lambs, aged between 10-12 months,
were randomly assigned to either Treatment (n=9) or Control (n=9) groups. Lambs
in the Treatment group received feed containing a novel endophyte-infested
perennial ryegrass seed, commencing on Day 0 of the Feeding phase with a low
induction dose, then increasing after 3 days to provide 0.16 mg/kg live bodywight
(LBW)/day of lolitrem B and 0.054 mg/kg LBW/day ergotamine. Lambs were examined
daily and when defined signs of PRGT were observed they were transferred to the
Testing phase. Neurological examinations, assessment of gait, surface
electromyography (EMG) and mechanosensory nociceptive threshold testing were
carried out and blood samples collected during both phases of the trial, with a
full necropsy, histopathological examination and measurement of faecal cortisol
metabolites (FCM) performed on Day 2 of the Testing phase. RESULTS Typical
clinical signs of PRGT, including ataxia of vestibulocerebellar origin leading to
stumbling, were observed in all Treatment lambs. The median interval from the
start of the Feeding phase to entry into the Testing phase was 21 (min 18, max
34) days. Histopathological characterisation of neurological lesions included the
presence of Purkinje cell vacuolation, pyknotic granular layer neurons and
proximal axonal Purkinje cell spheroids. Lesions were most apparent within the
vestibulocerebellum. Mean root-mean-square voltages from triceps EMG increased in
Treatment lambs between Feeding phase Day 0 and Testing phase Day 2 (p<0.001).
Daily water intake during the Testing phase for the Treatment group was less than
in Control group lambs (p=0.002), and concentrations of FCM at necropsy were
higher in Treatment compared to Control lambs (p=0.02). CONCLUSIONS AND CLINICAL
RELEVANCE Lolitrem B and ergotamine dosing in feed on a live weight basis
combined with neurological/gait assessment provides an effective model for
investigation of PRGT and potential therapeutics. Assessment of gait changes
using defined criteria and RMS voltages from EMG appear to be useful tools for
the assessment of the severity of neurological changes.
PMID- 29949722
TI - A Tale of Two Visual Systems: Invariant and Adaptive Visual Information
Representations in the Primate Brain.
AB - Visual information processing contains two opposite needs. There is both a need
to comprehend the richness of the visual world and a need to extract only
pertinent visual information to guide thoughts and behavior at a given moment. I
argue that these two aspects of visual processing are mediated by two
complementary visual systems in the primate brain-specifically, the
occipitotemporal cortex (OTC) and the posterior parietal cortex (PPC). The role
of OTC in visual processing has been documented extensively by decades of
neuroscience research. I review here recent evidence from human imaging and
monkey neurophysiology studies to highlight the role of PPC in adaptive visual
processing. I first document the diverse array of visual representations found in
PPC. I then describe the adaptive nature of visual representation in PPC by
contrasting visual processing in OTC and PPC and by showing that visual
representations in PPC largely originate from OTC.
PMID- 29949723
TI - Elementary Motion Detection in Drosophila: Algorithms and Mechanisms.
AB - Motion in the visual world provides critical information to guide the behavior of
sighted animals. Furthermore, as visual motion estimation requires comparisons of
signals across inputs and over time, it represents a paradigmatic and
generalizable neural computation. Focusing on the Drosophila visual system, where
an explosion of technological advances has recently accelerated experimental
progress, we review our understanding of how, algorithmically and
mechanistically, motion signals are first computed.
PMID- 29949724
TI - Racial-ethnic Disparities in Inflammation: Evidence of Weathering in Childhood?
AB - Building on the weathering hypothesis, we advance health disparities research by
assessing racial-ethnic differences in low-grade inflammation, a marker of
chronic stress exposure, in young children. Using nationally representative data
from the National Health and Nutrition Examination Survey (N = 6,652) and
logistic regression, we find an increased risk of low-grade inflammation among
Hispanic and African American children compared to white children. The risk of
inflammation appears to be stronger for Hispanic and African American children
with foreign-born parents compared to children of the same race-ethnicity with
U.S.-born parents. Low parental education and elevated child body mass index work
as partial mediators of these associations. Our findings suggest the need to
understand the psychosocial challenges faced by Hispanic and African American
children, particularly, those with foreign-born parents, if we are to make
further progress in reducing health disparities.
PMID- 29949726
TI - Ten Surprising Facts About Stressful Life Events and Disease Risk.
AB - After over 70 years of research on the association between stressful life events
and health, it is generally accepted that we have a good understanding of the
role of stressors in disease risk. In this review, we highlight that knowledge
but also emphasize misunderstandings and weaknesses in this literature with the
hope of triggering further theoretical and empirical development. We organize
this review in a somewhat provocative manner, with each section focusing on an
important issue in the literature where we feel that there has been some
misunderstanding of the evidence and its implications. Issues that we address
include the definition of a stressful event, characteristics of diseases that are
impacted by events, differences in the effects of chronic and acute events, the
cumulative effects of events, differences in events across the life course,
differences in events for men and women, resilience to events, and methodological
challenges in the literature. Expected final online publication date for the
Annual Review of Psychology Volume 70 is January 4, 2019. Please see
http://www.annualreviews.org/page/journal/pubdates for revised estimates.
PMID- 29949727
TI - Successful Memory Aging.
AB - For more than 50 years, psychologists, gerontologists, and, more recently,
neuroscientists have considered the possibility of successful aging. How to
define successful aging remains debated, but well-preserved age-sensitive
cognitive functions, like episodic memory, is an often-suggested criterion.
Evidence for successful memory aging comes from cross-sectional and longitudinal
studies showing that some older individuals display high and stable levels of
performance. Successful memory aging may be accomplished via multiple paths. One
path is through brain maintenance, or relative lack of age-related brain
pathology. Through another path, successful memory aging can be accomplished
despite brain pathology by means of efficient compensatory and strategic
processes. Genetic, epigenetic, and lifestyle factors influence memory aging via
both paths. Some of these factors can be promoted throughout the life course,
which, at the individual as well as the societal level, can positively impact
successful memory aging. Expected final online publication date for the Annual
Review of Psychology Volume 70 is January 4, 2019. Please see
http://www.annualreviews.org/page/journal/pubdates for revised estimates.
PMID- 29949728
TI - Meanings and Functions of Money in Different Cultural Milieus.
AB - We explore the psychological meanings of money that parallel its economic
functions. We explore money's ability to ascribe value, give autonomy, and
provide security for the future, and we show how each of these functions may play
out differently in different cultural milieus. In particular, we explore the
meanings and uses of money across ethnic groups and at different positions on the
socioeconomic ladder, highlighting changes over the last 50 years.We examine the
dynamics of redistribution between the individual, the family, and the state in
different cultures, and we analyze the gendering of money in the world of high
finance and in contexts of economic need. The field of behavioral economics has
illustrated how human psychology complicates the process of moving from normative
to descriptive models of human behavior; such complexity increases as we
incorporate the great diversity within human psychology. Expected final online
publication date for the Annual Review of Psychology Volume 70 is January 4,
2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised
estimates.
PMID- 29949725
TI - TRIM Proteins and Their Roles in Antiviral Host Defenses.
AB - Tripartite motif (TRIM) proteins are a versatile family of ubiquitin E3 ligases
involved in a multitude of cellular processes. Studies in recent years have
demonstrated that many TRIM proteins play central roles in the host defense
against viral infection. While some TRIM proteins directly antagonize distinct
steps in the viral life cycle, others regulate signal transduction pathways
induced by innate immune sensors, thereby modulating antiviral cytokine
responses. Furthermore, TRIM proteins have been implicated in virus-induced
autophagy and autophagy-mediated viral clearance. Given the important role of
TRIM proteins in antiviral restriction, it is not surprising that several viruses
have evolved effective maneuvers to neutralize the antiviral action of specific
TRIM proteins. Here, we describe the major antiviral mechanisms of TRIM proteins
as well as viral strategies to escape TRIM-mediated host immunity.
PMID- 29949729
TI - Creation of a predictive equation to estimate fat-free mass and the ratio of fat
free mass to skeletal size using morphometry in lean working farm dogs.
AB - AIMS To develop an equation that accurately estimates fat-free mass (FFM) and the
ratio of FFM to skeletal size or mass, using morphometric measurements in lean
working farm dogs, and to examine the association between FFM derived from body
condition score (BCS) and FFM measured using isotope dilution. METHODS Thirteen
Huntaway and seven Heading working dogs from sheep and beef farms in the Waikato
region of New Zealand were recruited based on BCS (BCS < 3, 3-4, > 4) using a
nine-point scale. Bodyweight, BCS, and morphometric measurements (head length and
circumference, body length, thoracic girth, and fore and hind limb length) were
recorded for each dog, and body composition was measured using an isotopic
dilution technique. A new variable using morphometric measurements, termed
skeletal size, was created using principal component analysis. Models for
predicting FFM, leanST (FFM minus skeletal mass) and ratios of FFM and leanST to
skeletal size or mass were generated using multiple linear regression analysis.
RESULTS Mean FFM of the 20 dogs, measured by isotope dilution, was 22.1 (SD 4.4)
kg and the percentage FFM of bodyweight was 87.0 (SD 5.0)%. Median BCS was 3.0
(min 1, max 6). Bodyweight, breed, age and skeletal size or mass were associated
with measured FFM (p<0.001). There was a good correlation between predicted FFM
and measured FFM (R2=0.96), and for the ratio of predicted FFM to skeletal size
and measured values (R2=0.99). Correlation coefficients were higher for the ratio
FFM and leanST to skeletal size than for ratios using skeletal mass. There was a
positive correlation between BCS-derived fat mass as a percentage of bodyweight
and fat mass percentage determined using isotope dilution (R2=0.65). CONCLUSIONS
AND CLINICAL RELEVANCE As expected, the predictive equation was accurate in
estimating FFM when tested on the same group of dogs used to develop the
equation. The significance of breed, independent of skeletal size, in predicting
FFM indicates that individual breed formulae may be required. Future studies that
apply these equations on a greater population of working Huntaway and Heading
dogs are needed to establish the utility of these equations on a large scale.
Such studies could ascertain if there is a ratio for lean mass to skeletal size
below which the risk of injury or disease increases. If these equations prove
useful they would provide an objective and non-invasive measure to determine when
welfare in individual dogs is compromised by underfeeding.
PMID- 29949730
TI - The Clean India Mission: Public and animal health benefits.
AB - The Clean India Mission is a national campaign that aims for complete elimination
of open defecation from the country. In India, 564 million people do not have
access to toilets and defecate in the open environment. The 'Millennium
development goals' have given increased weightage to elimination of open
defecation for improving health, nutrition and productivity of developing country
populations. The Indian economy bears an estimated annual total loss (in terms of
health, education, access time and tourism) of US$ 54 billion due to lack of
toilets, poor hygiene and over US$ 38.5 billion in treatment costs for diseases
occurring due to poor hygiene. Out of 1415 human pathogens, at least more than
10% of pathogens are transmitted through the faecal-oral route. The practice of
open defecation helps pathogens persist in the environment and cause diseases.
This review focuses on the current status and harms of open defecation, as well
as the public and animal health benefits of implementing 'The Clean India
Mission' in India.
PMID- 29949731
TI - The importance of on-farm biosecurity: Sero-prevalence and risk factors of
bacterial and viral pathogens in smallholder pig systems in Uganda.
AB - BACKGROUND: The productivity of pigs in smallholder systems is affected by high
disease burden, most of which might not be obvious, with their epidemiology and
impact being poorly understood. This study estimated the seroprevalence and
identified the risk factors of a range of bacterial and viral pathogens of
potential economic and public health importance in domestic pigs in Uganda. A
total of 522 clinically healthy pigs were randomly selected from 276 pig farms in
Masaka (142) and Lira (134) districts of Uganda in 2015. RESULTS: Overall the
highest animal prevalence was found for Streptococcus suis 73.0% (CI95: 67.0
78.3) in Lira and 68.2% (CI95: 62.7-73.4) in Masaka; followed by Porcine
circovirus type 2 with 50.8% (CI95: 44.5-57.2) in Lira and 40.7% (CI95: 35.2
46.5) in Masaka and Actinobacillus pleuro-pneumoniae, 25.6% (CI95: 20.4-31.6) in
Lira and 20.5% (CI95: 16.2-25.6) in Masaka. Mycoplasma hyopneumonia prevalence
was 20.9% (CI95: 16.2-26.6) in Lira and 10.1% (CI95: 7.1-14.1) in Masaka, while
Porcine parvovirus was 6.2% (CI95: 4.0-9.7) in Masaka and 3.4% (CI95: 1.7-6.6) in
Lira. Less common pathogens were Influenza A, 8.5% (CI95: 5.6-12.8) in Lira and
2.0% (CI95: 0.9-4.5) in Masaka and Porcine Reproductive and Respiratory Syndrome
Virus, 1.7% (CI95: 0.7-4.3) in Lira and 1.3% (CI95: 0.5-3.5) in Masaka. Even less
common was Rotavirus A with 0.8% (CI95: 0.2-3.0) in Lira and 0.7% (CI95: 0.2-2.5)
in Masaka; the same was for Aujeszky virus with 0.4% (CI95: 0.7-2.4) in Lira and
0.0% (CI95: 0.0-0.1) in Masaka. Co-infection with two pathogens was common and
there was a significant association of M. hyo and PCV2 co-occurrence (p = 0.016).
Multivariate analysis showed that for S. suis the use of disinfectant reduced
odds of sero-positivitey (OR = 0.15; p = 0.017) and pigs less than 6 months were
more likely to be infected than older pigs (OR = 3.35; p = 0.047). For M. hyo,
crossbred pigs had higher odd of infection compared to local breeds (OR = 1.59; p
< 0.001). CONCLUSIONS: The studied pathogens have high prevalences in smallholder
pig production systems and might be silent killers, thus affecting productivity
and there is a possibility that some pathogens could spread to humans. Given the
limited knowledge of veterinary workers and the poor diagnostic capacities and
capabilities in these systems, the diseases are potentially usually under
diagnosed. These findings constitute baseline data to measure the impact of
future interventions aiming to reduce disease burden in the pig production
systems in Uganda.
PMID- 29949732
TI - Working definitions, subjective and objective assessments and experimental
paradigms in a study exploring social withdrawal in schizophrenia and Alzheimer's
disease.
AB - Social withdrawal is one of the first and common signs of early social
dysfunction in a number of important neuropsychiatric disorders, likely because
of the enormous amount and complexity of brain processes required to initiate and
maintain social relationships (Adolphs, 2009). The Psychiatric Ratings using
Intermediate Stratified Markers (PRISM) project focusses on the shared and unique
neurobiological basis of social withdrawal in schizophrenia, Alzheimer and
depression. In this paper, we discuss the working definition of social withdrawal
for this study and the selection of objective and subjective rating scales to
assess social withdrawal chosen or adapted for this project. We also discuss the
MRI and EEG paradigms selected to study the systems and neural circuitry thought
to underlie social functioning and more particularly to be involved in social
withdrawal in humans, such as the social perception and the social affiliation
networks. A number of behavioral paradigms were selected to assess complementary
aspects of social cognition. Also, a digital phenotyping method (a smartphone
application) was chosen to obtain real-life data.
PMID- 29949733
TI - Neuropeptide modulation of addiction: Focus on galanin.
AB - Addiction is a chronic, relapsing disorder characterised by the use of a
substance or act to the point of compulsion. There are a number of medical
treatments available for the intervention of these disorders, however, the
effectiveness of current therapeutics is far from adequate. Neuropeptides are
known to modulate addictive behaviours and may provide new therapeutic targets
for the treatment of substance abuse. Accumulating evidence has suggested galanin
as a potential important neuromodulator of addiction. Both human genetic studies
and animal models have highlighted a role for this neuropeptide in affective
disorders, as well as alcohol, nicotine, and opiate dependence. This review
highlights the role of galanin and other primary neuropeptides implicated in
modulating addiction to different drugs of abuse. Orexin, relaxin-3,
corticotrophin-releasing factor, dynorphin and enkephalin, are also discussed
given their involvement in mediating reward-seeking behaviour.
PMID- 29949734
TI - Prenatal stress disrupts social behavior, cortical neurobiology and commensal
microbes in adult male offspring.
AB - In utero and early neonatal exposure to maternal stress is linked with
psychiatric disorders, and the underlying mechanisms are currently being
elucidated. We used a prenatal stressor in pregnant mice to examine novel
relationships between prenatal stress exposure, changes in the gut microbiome,
and social behavior. Here, we show that males exposed to prenatal stress had a
significant reduction in social behavior in adulthood, with increased
corticosterone release following social interaction. Male offspring exposed to
prenatal stress also had neuroinflammation, decreased oxytocin receptor, and
decreased serotonin metabolism in their cortex in adulthood, which are linked to
decreased social behavior. Finally, we found a significant difference in
commensal microbes, including decreases in Bacteroides and Parabacteroides, in
adult male offspring exposed to prenatal stress when compared to non-stressed
controls. Our findings indicate that gestation is a critical window where
maternal stress contributes to the development of aberrant social behaviors and
alterations in cortical neurobiology, and that prenatal stress is sufficient to
disrupt the male gut-brain axis into adulthood.
PMID- 29949735
TI - Modulation of Kalirin-7 expression by hippocampal CA1 5-HT1B receptors in spatial
memory consolidation.
AB - Serotonin 5-HT1B receptors (5-HT1BRs) are distributed in hippocampal CA1 and play
a pivotal role in cognitive function. Activation of 5-HT1BRs regulates synaptic
plasticity at the excitatory synapses in the hippocampus. However, the role and
its underlying mechanism of 5-HT1BR activation-mediated glutamatergic synaptic
plasticity in spatial memory are not fully understood. In this study, spatial
memory of Sprague-Dawley (SD) rats was assessed in a Morris water maze after
bilateral dorsal hippocampal CA1 infusion of the 5-HT1BR antagonist GR55562 (25
MUg/MUL) or agonist CP93129 (25 MUg/MUL). GR55562 did not affect the spatial
memory acquisition but significantly increased the target quadrant preference
during the memory consolidation probe performed 14 d after the training session,
while CP93129 impaired the memory consolidation process. Moreover, GR55562
significantly increased, while CP93129 significantly decreased, the density of
dendritic spines on the distal apical dendrites of CA1 pyramidal neurons.
Furthermore, western blot experiments indicated that GR55562 significantly
increased, but CP93129 significantly reduced, the expression of Kalirin-7 (Kal
7), PSD95, and GluA2/3 subunits of AMPA receptors. Our results suggest that Kal-7
and Kal-7-mediatedalteration of AMPA receptor subtype expression may play crucial
roles in the impact of hippocampal CA1 5-HT1BR activation on spatial memory
consolidation.
PMID- 29949736
TI - Clover-tagged porcine reproductive and respiratory syndrome virus infectious
clones for rapid detection of virus neutralizing antibodies.
AB - Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus
(PRRSV), is a widespread disease that affects domestic pigs of all ages. Accurate
and rapid detection of PRRSV specific neutralizing antibodies levels in a pig
herd is beneficial for the evaluation of the herd's immunity to combat the
specific viral infection. However, the current methods for viral detection,
including fluorescent focus neutralization (FFN) and cytopathic effect (CPE)
reduction neutralizing assays, are subjective and time-consuming. Therefore, a
Clover-tagged PRRSV virus neutralization assay were developed that instrumentally
measures the fluorescence signal of Clover stably expressing by a PRRSV
infectious clone for at least 10 passages. Herein, the results showed that the
proposed Clover-tagged PRRSV neutralization assay is reliable using instrumental
measurements of the fluorescence signal of Clover and allows for rapid detection
of neutralizing antibodies against PRRSV. The assay was evaluated by testing
swine sera from experimental and field samples, and comparisons were made with
the traditional FFN and CPE reduction assays. These results suggest that the
Clover-tagged PRRSV infectious clone offers a fast and reliable testing method
for neutralizing antibodies and could permit high-throughput screening of new
antiviral agents.
PMID- 29949737
TI - An efficient recovery method for enteric viral particles from agricultural soils.
AB - Enteric viruses have been recognized as the leading cause of non-bacterial
gastroenteritis and hepatitis outbreaks around the world. Understanding their
prevalence and persistence in the environment is important for the effective
control of these infections. The aim of this study was to develop an efficient
recovery procedure for viral infectious particles from agricultural soils.
Samples (25 g) of soil (black earth soil, loamy soil, and sandy soil) were spiked
with murine norovirus (MNV) and feline calicivirus (FCV), mixed with five
different buffers and viral genetic material was extracted by 3 commercial kits.
The combination consisted by the modified Eagle's medium buffer followed by
Dynabeads nucleic acid extraction kit, when the detection is conducted by
molecular biology, has been identified as being the most effective procedure to
preserve the viral particle infectivity and also to remove PCR inhibitors. The
recovery percentages of infectious MNV for the 3 types of soils were 54.3%,
54.4%, and 56.9%. In contrast, the titres of the FCV varied depending on the type
of soil, and the recovery percentages were 47.8% in the black soil, 15.6% in the
loamy soil, and 17.7% in the sandy soil. Also, the results presented in this
study highlight the importance of using an internal process control such as
artificial inoculation with MNV at known concentrations during detection by
molecular methods, in order to avoid the occurrence of false negative reactions.
PMID- 29949738
TI - Current Readings: Single vs Bilateral Internal Mammary Artery in Coronary Artery
Bypass Grafting.
AB - There is strong retrospective data demonstrating that bilateral internal mammary
artery (BIMA) grafting leads to better long-term survival as compared to left
internal mammary artery grafting. However, this survival advantage was not
corroborated by the interim results of the Arterial Revascularization Trial.
Today, there are barriers to widespread adoption of BIMA grafting. One of the
main disadvantages of the use of BIMA grafts is the higher risk of deep sternal
wound infection. Deep sternal wound infections can be minimized by skeletonized
harvesting of the internal mammary artery grafts, which preserve blood flow to
the sternum. Also, utilizing the BIMA graft as a "Y" graft may lead to more
complete revascularization compared to its in situ use. BIMA grafting on average
takes 25 minutes longer operating time with a higher in-hospital costs. We
eagerly await the 10-year results of the Arterial Revascularization Trial to
determine the truly unbiased randomized long-term effectiveness of BIMA grafting.
PMID- 29949739
TI - Mixed-phenotype large granular lymphocytic leukemia: a rare subtype in the large
granular lymphocytic leukemia spectrum.
AB - Large granular lymphocytic leukemia (LGLL) is a chronic proliferation of
cytotoxic lymphocytes in which more than 70% of patients develop cytopenia(s)
requiring therapy. LGLL includes T-cell LGLL and chronic lymphoproliferative
disorder of natural killer (NK) cells. The neoplastic cells in LGLL usually
exhibit a single immunophenotype in a patient, with CD8-positive/alphabeta T-cell
type being the most common, followed by NK-cell, gammadelta T-cell, and CD4
positive/alphabeta T-cell types. We investigated a total of 220 LGLL cases and
identified 12 mixed-phenotype LGLLs (5%): 7 cases with coexistent alphabeta T
cell and NK-cell clones and 5 with coexistent alphabeta and gammadelta T-cell
clones. With a median follow-up of 48 months, the clinicopathological
characteristics of these patients seemed similar to those of typical LGLL
patients. Treatment was instituted in 9 patients, and 5 patients (55%) attained
complete hematologic response or partial response. The therapeutic response rate
of this cohort is comparable to the reported overall response rate of 40% to 60%
in typical LGLL patients. Three patients who did not receive any treatment had
progressive or persistent cytopenias. Interestingly, inverted proportions of 2
clones at disease recurrence were identified in 4 patients (36%) and stable
clonal proportions in 7 patients (64%). Mixed-phenotype LGLL is rare, and this
study underscores the importance of recognizing this rare type of LGLL in
patients who may benefit from LGLL treatment.
PMID- 29949740
TI - Fluorescence in situ hybridization for the diagnosis of NPHP1 deletion-related
nephronophthisis on renal biopsy.
AB - Nephronophthisis is an autosomal recessive tubulointerstitial nephropathy that is
a leading genetic etiology of end-stage renal disease in children and young
adults. Approximately 60% of patients with a known genetic etiology of
nephronophthisis are due to homozygous deletion of the NPHP1 gene. We identified
a total of 45 renal biopsies from young patients with chronic kidney disease of
undetermined etiology and analyzed them for the possibility of nephronophthisis
due to NPHP1 deletion using interphase fluorescence in situ hybridization and/or
polymerase chain reaction. Homozygous NPHP1 deletion was identified in 9 patients
(20%). In cases with adequate tissue, both assays were performed and showed 100%
agreement. Blinded histopathologic analysis was then performed and identified 6
lesions that were significantly more common in biopsies from patients with NPHP1
deletion-proven nephronophthisis than chronic kidney injury of other known
etiologies. Many of the classically described nephronophthisis biopsy lesions
such as tubular basement membrane duplication, presence of cysts, and mononuclear
interstitial inflammation were not significantly associated with this disease
when compared with biopsies from patients with chronic kidney injury due to other
etiologies. There were, however, morphologic lesions that were strongly
associated with NPHP1 deletion including tubular abnormalities such as
diverticulum, florets, and macula densa-like change as well as interstitial Tamm
Horsfall aggregates, periglomerular fibrosis, and the absence of
arteriosclerosis. Awareness of the histopathologic pattern of injury in
nephronophthisis combined with testing for NPHP1 deletion enables renal
pathologists to provide a definitive pathologic and genetic diagnosis in a subset
of patients with this disease.
PMID- 29949741
TI - Genomic structures of dysplastic nodule and concurrent hepatocellular carcinoma.
AB - Although high-grade dysplastic nodule (HGDN) is a preneoplastic lesion that
precedes hepatocellular carcinoma (HCC), the genomic structures of HGDN in
conjunction with HCC remain elusive. The objective of this study was to identify
genomic alterations of HGDN and its difference from HCC that may drive HGDN
progression to HCC. We analyzed 16 regions of paired HGDN and HCC from 6 patients
using whole-exome sequencing to find somatic mutation and copy number alteration
(CNA) profiles of HGDN and HCC. The numbers of mutations, driver mutations, and
CNAs of HGDNs were not significantly different from those of HCCs. We identified
that the CNA gain of 1q25.3-1q42.13 was predominant in the HCCs compared with
that in the HGDNs. Two cases (one nodule-in-nodule case and another case with
closely attached HCC and HGDN) showed several overlapped driver mutations (CTNNB1
and CEBPA) and CNAs (losses of CDKN2A, RB1, and TP53) between HGDNs and HCCs,
suggesting their roles in the early HCC development. The other 4 cases with
spatially separated HCCs and HGDNs showed few overlapped alterations between the
paired HCCs and HGDNs. Mutations in ERBB2 and CCND1, and CNAs (gains of CTNNB1,
MET, and SMO and losses of PTEN, TP53, and SETD2) were identified as "HCC
predominant," suggesting their roles in the progression of HGDN to HCC. Our data
show that HCCs are direct descendants of HGDNs in some cases, but there is no
direct evidence of such relationship in spatially separated cases. Genomic
features of HGDN identified in this study provide a useful resource for
dissecting clues for the genetic diagnosis of HGDN and HCC.
PMID- 29949742
TI - Microglandular adenosis of the breast: a deceptive and still misterious benign
lesion.
AB - Microglandular adenosis of the breast (MA), a benign glandular proliferation, was
originally described about 35years ago. The lesion, is constituted by small
glands all of the same size. Glands are lined by one layer of cuboidal epithelial
cells encircled by basal lamina without any evidence of interposed myoepithelial
elements. Cells are positive for low weight keratins and S-100 protein and
negative for ER, PR and HER 2. Since then, in the years, several malignant
lesions all showing microglandular architecture have been regarded either as a
precursor or an equivalent manifestation of MA. The latter has been associated to
a large number of malignancies that include DCIS, LCIS, ademyoepithelioma, high
grade basal like carcinoma, adenoid cystic carcinoma, matrix producing carcinoma,
invasive duct carcinoma NOS, spindle cell carcinoma, not to mention acinic cell
carcinoma. None of the above tumors were identical to MA. Differences mainly
rested not only on the specific structure of the small glands but also on the
cytological composition and immunohistochemical features of different lesions.
Here a review of the features of MA together with the differential diagnosis with
lesions showing microglandular structure is discussed. MA shows similarities with
a lesion named microglandular hamartoma/adenosis (MH) of the nasal cavity. The
relation of the two similar lesions is discussed.
PMID- 29949743
TI - Bicuculline Reverts the Neuroprotective Effects of Meloxicam in an Oxygen and
Glucose Deprivation (OGD) Model of Organotypic Hippocampal Slice Cultures.
AB - We previously demonstrated that the non-steroidal anti-inflammatory agent
meloxicam has neuroprotective effects in an oxygen and glucose deprivation model
(OGD) of rat organotypic hippocampal slice cultures. We wondered if GABAergic
transmission changed the neuroprotective effects of meloxicam and if meloxicam
was able to modulate endoplasmic reticulum stress (ER stress) in this model.
Mortality was measured using propidium iodide. Western blot assays were performed
to measure levels of cleaved and non-cleaved caspase-3 to quantify apoptosis,
while levels of GRP78, GRP94 and phosphorylated eIF2alpha were used to detect
unfolded protein response (UPR). Transcript levels of GRP78, GRP94 and GABAergic
receptor alpha, beta, and gamma subunits were measured by real-time quantitative
polymerase chain reaction (qPCR). In the present study, we show that the presence
of meloxicam in a 30 min OGD assay, followed by 24 h of normoxic conditions,
presented an antiapoptotic effect. The simultaneous presence of the GABAA
receptor antagonist, bicuculline, in combination with meloxicam blocked the
neuroprotective effect provided by the latter. However, in light of its effects
on caspase 3 and PARP, bicuculline did not seem to promote the apoptotic pathway.
Our results also showed that meloxicam modified the unfolded protein response
(UPR), as well as the transcriptional response of different genes, including the
GABAA receptor, alpha1, beta3 and gamma2 subunits. We concluded that meloxicam
has a neuroprotective anti-apoptotic action, is able to enhance the UPR
independently of the systemic anti-inflammatory response and its neuroprotective
effect can be inhibited by blocking GABAA receptors.
PMID- 29949744
TI - Postnatal Changes in K+/Cl- Cotransporter-2 Expression in the Forebrain of Mice
Bearing a Mutant Nicotinic Subunit Linked to Sleep-Related Epilepsy.
AB - The Na+/K+/Cl- cotransporter-1 (NKCC1) and the K+/Cl- cotransporter-2 (KCC2) set
the transmembrane Cl- gradient in the brain, and are implicated in
epileptogenesis. We studied the postnatal distribution of NKCC1 and KCC2 in wild
type (WT) mice, and in a mouse model of sleep-related epilepsy, carrying the
mutant beta2-V287L subunit of the nicotinic acetylcholine receptor (nAChR). In WT
neocortex, immunohistochemistry showed a wide distribution of NKCC1 in neurons
and astrocytes. At birth, KCC2 was localized in neuronal somata, whereas at
subsequent stages it was mainly found in the somatodendritic compartment. The
cotransporters' expression was quantified by densitometry in the transgenic
strain. KCC2 expression increased during the first postnatal weeks, while the
NKCC1 amount remained stable, after birth. In mice expressing beta2-V287L, the
KCC2 amount in layer V of prefrontal cortex (PFC) was lower than in the control
littermates at postnatal day 8 (P8), with no concomitant change in NKCC1.
Consistently, the GABAergic excitatory to inhibitory switch was delayed in PFC
layer V of mice carrying beta2-V287L. At P60, the amount of KCC2 was instead
higher in mice bearing the transgene. Irrespective of genotype, NKCC1 and KCC2
were abundantly expressed in the neuropil of most thalamic nuclei since birth.
However, KCC2 expression decreased by P60 in the reticular nucleus, and more so
in mice expressing beta2-V287L. Therefore, a complex regulatory interplay occurs
between heteromeric nAChRs and KCC2 in postnatal forebrain. The pathogenetic
effect of beta2-V287L may depend on altered KCC2 amounts in PFC during
synaptogenesis, as well as in mature thalamocortical circuits.
PMID- 29949745
TI - Novel synergistic transparent k-Carrageenan/Xanthan gum/Gellan gum hydrogel film:
Mechanical, thermal and water barrier properties.
AB - The aim is to develop novel synergistic transparent k-Carrageenan/Xanthan
gum/Gellan gum (k-C/X/G) hydrogel films with different weight ratio composition
and to study the effect of these compositions on the physical properties of the
films. The structure and morphological properties of the films were investigated
by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy
(SEM), X-ray diffraction (XRD) and differential scanning calorimeter (DSC).
Results for FT-IR, DSC and SEM analysis showed a clear interaction between k-C,
X, and G to form a new material. The mechanical, thermal and water barrier
properties such as water vapor permeability (WVP), water contact angle (WCA) and
moisture content were determined. The temperature at 5% weight loss (T5%) are in
the range of 64.2-121.9 degrees C. The WVP exhibits are in the range of 1.8-2.4,
contact angle are in the range of 32-65.8 degrees and moisture content 16.5
21.51. The hydrogel film had good tensile strength of 19.1-31.0 MPa and
elongation at break of 13-19% and tensile modulus of 1.6-2.4 GPa. The UV results
indicate that the films were very transparent. The range of properties of the
ternary k-C/X/G hydrogel films suggest that the presence molecular interaction
and cross linking within the blends.
PMID- 29949746
TI - Effect of fibrillation conditions on the anti-amyloidogenic properties of
polyphenols and their involved mechanisms.
AB - In the present study, we have investigated the effects of protein concentration
and stirring on the in vitro assembly of Hen Egg White Lysozyme (HEWL),
particularly with regard to the aggregate morphology and anti-amyloidogenic
properties of two naturally occurring polyphenols, taxifolin and silibinin. The
results obtained clearly demonstrated that applying stirring and concentration
enhancement alter the amount as well as morphology of amyloid fibrils formed.
Additionally, latter aggregates exhibited higher affinity for amyloid-specific
dyes. The second part of the present investigation was devoted to studies
involving anti-amyloidogenic properties of selected polyphenols. Importantly, we
found that the potency of polyphenols to inhibit HEWL amyloid fibrillation and
related toxicity is strongly dependent on the amyloidogenic conditions in which
amyloid fibrils are produced. Based on obtained data, under condition where the
rate of protein assembly is high (higher protein concentration and stirring), the
capacity of polyphenols to inhibit HEWL fibrillogenesis and related cytotoxicity
may dramatically decrease. Similar results were obtained when we used taxifolin
to inhibit bovine insulin amyloid fibrillation. Additionally, amyloidogenic
conditions may also affect the mechanism by which these molecules inhibit HEWL
fibrillation. The possible mechanism by which selected polyphenols exert their
inhibitory effects, under various experimental conditions, is also discussed.
PMID- 29949747
TI - Effects of glycation on human gammad-crystallin proteins by different glycation
inducing agents.
AB - Human gammad-crystallin (Hgammad-crystallin), a major protein component of the
human eye lens, is associated with the development of juvenile- and mature-onset
cataracts. Evidence suggests that nonenzymatic protein glycation plays an
important role in the aetiology of cataract and diabetic sequelae. This research
compared the effects of various glycation modifiers on Hgammad-crystallin
aggregation, by treating samples of Hgammad-crystallin with ribose, galactose, or
methylglyoxal using several biophysical techniques. To measure advanced glycation
end products, an Nepsilon-(carboxyethyl)lysine enzyme-linked immunosorbent assay
was performed on the glycating agent-treated Hgammad-crystallin samples.
Fructosamine production detection was performed for both ribose-treated and
galactose-treated samples. Methylglyoxal-treated samples had the highest level of
aggregation and the greatest extent of unfolding, and upon incubation for a
minimum of 12 days, exhibited a marked enhancement in the amount of Nepsilon
(carboxyethyl)lysine. The molecular profiles and morphological features of the
glycated samples were highly correlated to the type of glycation agent used.
These findings highlight a close connection between the type of glycation
modifier and the various aggregation species that form. Thus, these results may
facilitate deciphering of the molecular mechanism of diabetic cataractogenesis.
PMID- 29949748
TI - An in-silico method for identifying aggregation rate enhancer and mitigator
mutations in proteins.
AB - Newly synthesized polypeptides must pass stringent quality controls in cells to
ensure appropriate folding and function. However, mutations, environmental
stresses and aging can reduce efficiencies of these controls, leading to
accumulation of protein aggregates, amyloid fibrils and plaques. In-vitro
experiments have shown that even single amino acid substitutions can drastically
enhance or mitigate protein aggregation kinetics. In this work, we have collected
a dataset of 220 unique mutations in 25 proteins and classified them as enhancers
or mitigators on the basis of their effect on protein aggregation rate. The data
were analyzed via machine learning to identify features capable of distinguishing
between aggregation rate enhancers and mitigators. Our initial Support Vector
Machine (SVM) model separated such mutations with an overall accuracy of 69%.
When local secondary structures at the mutation sites were considered, the
accuracies further improved by 13-15%. The machine-learnt features are distinct
for each secondary structure class at mutation sites. Protein stability and
flexibility changes are important features for mutations in alpha-helices. beta
strand propensity, polarity and charge become important when mutations occur in
beta-strands and ability to form secondary structure, helical tendency and
aggregation propensity are important for mutations lying in coils. These results
have been incorporated into a sequence-based algorithm (available at
http://www.iitm.ac.in/bioinfo/aggrerate-disc/) capable of predicting whether a
mutation will enhance or mitigate a protein's aggregation rate. This algorithm
will find several applications towards understanding protein aggregation in human
diseases, enable in-silico optimization of biopharmaceuticals and enzymes for
improved biophysical attributes and de novo design of bio-nanomaterials.
PMID- 29949750
TI - Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically
Disordered Protein Polymers.
AB - Proteins and synthetic polymers can undergo phase transitions in response to
changes to intensive solution parameters such as temperature, proton chemical
potentials (pH), and hydrostatic pressure. For proteins and protein-based
polymers, the information required for stimulus-responsive phase transitions is
encoded in their amino acid sequence. Here, we review some of the key physical
principles that govern the phase transitions of archetypal intrinsically
disordered protein polymers (IDPPs). These are disordered proteins with
repetitive amino acid sequences. Advances in recombinant technologies have
enabled the design and synthesis of protein sequences of a variety of sequence
complexities and lengths. We summarize insights that have been gleaned from the
design and characterization of IDPPs that undergo thermo-responsive phase
transitions and build on these insights to present a general framework for IDPPs
with pH and pressure responsive phase behavior. In doing so, we connect the
stimulus-responsive phase behavior of IDPPs with repetitive sequences to the coil
to-globule transitions that these sequences undergo at the single-chain level in
response to changes in stimuli. The proposed framework and ongoing studies of
stimulus-responsive phase behavior of designed IDPPs have direct implications in
bioengineering, where designing sequences with bespoke material properties
broadens the spectrum of applications, and in biology and medicine for
understanding the sequence-specific driving forces for the formation of protein
based membraneless organelles as well as biological matrices that act as
scaffolds for cells and mediators of cell-to-cell communication.
PMID- 29949749
TI - Expression, functional analysis and mutation of a novel neutral zearalenone
degrading enzyme.
AB - The crops and grains were often contaminated by high level of mycotoxin
zearalenone (ZEN). In order to remove ZEN and keep food safe, ZEN-degrading or
detoxifying enzymes are urgently needed. Here, a newly identified
lactonohydrolase responsible for the detoxification of ZEN, annotated as Zhd518,
was expressed and characterized. Zhd518 showed 65% amino acid identity with
Zhd101, which was widely studied for its ZEN-degrading ability. A detailed
activity measurement method of ZEN-degrading enzyme was provided. Biochemical
analysis indicated that the purified recombinant Zhd518 from E. coli exhibited a
high activity against ZEN (207.0 U/mg), with the optimal temperature and pH of 40
degrees C and 8.0, respectively. The Zhd518 can degrade ZEN derivatives, and the
specific activities against alpha-Zearalenol, beta-Zearalenol, alpha-Zearalanol
and beta-Zearalanol were 23.0 U/mg, 64.7 U/mg, 119.8 U/mg and 66.5 U/mg,
respectively. The active sites of Zhd518 were predicted by structure modeling and
determined by mutation analysis. A point mutant N156H exhibited 3.3-fold activity
against alpha-Zearalenol comparing to Zhd518. Zhd518 is the first reported
neutral and the second characterized ZEN-degrading enzyme, which provides a new
and more excellent candidate for ZEN detoxifying in food and feed industry.
PMID- 29949751
TI - Mass Spectrometry-based Structural Analysis and Systems Immunoproteomics
Strategies for Deciphering the Host Response to Endotoxin.
AB - One cause of sepsis is systemic maladaptive immune response of the host to
bacteria and specifically, to Gram-negative bacterial outer-membrane glycolipid
lipopolysaccharide (LPS). On the host myeloid cell surface, proinflammatory LPS
activates the innate immune system via Toll-like receptor-4/myeloid
differentiation factor-2 complex. Intracellularly, LPS is also sensed by the
noncanonical inflammasome through caspase-11 in mice and 4/5 in humans. The
minimal functional determinant for innate immune activation is the membrane
anchor of LPS called lipid A. Even subtle modifications to the lipid A scaffold
can enable, diminish, or abolish immune activation. Bacteria are known to modify
their LPS structure during environmental stress and infection of hosts to alter
cellular immune phenotypes. In this review, we describe how mass spectrometry
based structural analysis of endotoxin helped uncover major determinations of
molecular pathogenesis. Through characterization of LPS modifications, we now
better understand resistance to antibiotics and cationic antimicrobial peptides,
as well as how the environment impacts overall endotoxin structure. In addition,
mass spectrometry-based systems immunoproteomics approaches can assist in
elucidating the immune response against LPS. Many regulatory proteins have been
characterized through proteomics and global/targeted analysis of protein
modifications, enabling the discovery and characterization of novel endotoxin
mediated protein translational modifications.
PMID- 29949752
TI - ConfocalVR: Immersive Visualization for Confocal Microscopy.
AB - ConfocalVR is a virtual reality (VR) application created to improve the ability
of researchers to study the complexity of cell architecture. Confocal microscopes
take pictures of fluorescently labeled proteins or molecules at different focal
planes to create a stack of two-dimensional images throughout the specimen.
Current software applications reconstruct the three-dimensional (3D) image and
render it as a two-dimensional projection onto a computer screen where users need
to rotate the image to expose the full 3D structure. This process is mentally
taxing, breaks down if you stop the rotation, and does not take advantage of the
eye's full field of view. ConfocalVR exploits consumer-grade VR systems to fully
immerse the user in the 3D cellular image. In this virtual environment, the user
can (1) adjust image viewing parameters without leaving the virtual space, (2)
reach out and grab the image to quickly rotate and scale the image to focus on
key features, and (3) interact with other users in a shared virtual space
enabling real-time collaborative exploration and discussion. We found that
immersive VR technology allows the user to rapidly understand cellular
architecture and protein or molecule distribution. We note that it is impossible
to understand the value of immersive visualization without experiencing it first
hand, so we encourage readers to get access to a VR system, download this
software, and evaluate it for yourself. The ConfocalVR software is available for
download at http://www.confocalvr.com, and is free for nonprofits.
PMID- 29949753
TI - Polarized Organization of the Cytoskeleton: Regulation by Cell Polarity Proteins.
AB - Polarity is one of the fundamental properties displayed by living organisms. In
metazoans, cell polarity governs developmental processes and plays an essential
role during maintenance of forms of tissues as well as their functions. The
mechanisms of establishment and maintenance of cell polarity have been
investigated extensively in the last two decades. This has resulted in
identification of "core cell polarity modules" that control anterior-posterior,
front-rear and apical-basal polarity across various cell types. Here, we review
how these polarity modules interact closely with the cytoskeleton during
establishment and maintenance of cytoskeletal polarity. We further suggest that
reciprocal interactions between cell polarity modules and the cytoskeleton
consolidate the initial weaker polarity, arising from an external cue, into a
committed polarized system.
PMID- 29949754
TI - A Mouse Ependymoma Model Provides Molecular Insights into Tumor Formation.
AB - Ozawa et al. present a murine tumor model resembling the most frequent molecular
group of human supratentorial ependymoma, ST-EPN-RELA. Their model shows RELA
fusion-based de novo ependymoma tumorigenesis in the forebrain derived from
neural stem cells.
PMID- 29949755
TI - MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid beta-Oxidation.
AB - Micropeptide regulator of beta-oxidation (MOXI) is a conserved muscle-enriched
protein encoded by an RNA transcript misannotated as non-coding. MOXI localizes
to the inner mitochondrial membrane where it associates with the mitochondrial
trifunctional protein, an enzyme complex that plays a critical role in fatty acid
beta-oxidation. Isolated heart and skeletal muscle mitochondria from MOXI
knockout mice exhibit a diminished ability to metabolize fatty acids, while
transgenic MOXI overexpression leads to enhanced beta-oxidation. Additionally,
hearts from MOXI knockout mice preferentially oxidize carbohydrates over fatty
acids in an isolated perfused heart system compared to wild-type (WT) animals.
MOXI knockout mice also exhibit a profound reduction in exercise capacity,
highlighting the role of MOXI in metabolic control. The functional
characterization of MOXI provides insight into the regulation of mitochondrial
metabolism and energy homeostasis and underscores the regulatory potential of
additional micropeptides that have yet to be identified.
PMID- 29949756
TI - Mitoregulin: A lncRNA-Encoded Microprotein that Supports Mitochondrial
Supercomplexes and Respiratory Efficiency.
AB - Mitochondria are composed of many small proteins that control protein synthesis,
complex assembly, metabolism, and ion and reactive oxygen species (ROS) handling.
We show that a skeletal muscle- and heart-enriched long non-coding RNA,
LINC00116, encodes a highly conserved 56-amino-acid microprotein that we named
mitoregulin (Mtln). Mtln localizes to the inner mitochondrial membrane, where it
binds cardiolipin and influences protein complex assembly. In cultured cells,
Mtln overexpression increases mitochondrial membrane potential, respiration
rates, and Ca2+ retention capacity while decreasing mitochondrial ROS and matrix
free Ca2+. Mtln-knockout mice display perturbations in mitochondrial respiratory
(super)complex formation and activity, fatty acid oxidation, tricarboxylic acid
(TCA) cycle enzymes, and Ca2+ retention capacity. Blue-native gel electrophoresis
revealed that Mtln co-migrates alongside several complexes, including the complex
I assembly module, complex V, and supercomplexes. Under denaturing conditions,
Mtln remains in high-molecular-weight complexes, supporting its role as a sticky
molecular tether that enhances respiratory efficiency by bolstering protein
complex assembly and/or stability.
PMID- 29949757
TI - Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the
Neighboring Normal Epithelial Cells.
AB - p53 is a tumor suppressor protein, and its missense mutations are frequently
found in human cancers. During the multi-step progression of cancer, p53
mutations generally accumulate at the mid or late stage, but not in the early
stage, and the underlying mechanism is still unclear. In this study, using
mammalian cell culture and mouse ex vivo systems, we demonstrate that when
p53R273H- or p53R175H-expressing cells are surrounded by normal epithelial cells,
mutant p53 cells undergo necroptosis and are basally extruded from the epithelial
monolayer. When mutant p53 cells alone are present, cell death does not occur,
indicating that necroptosis results from cell competition with the surrounding
normal cells. Furthermore, when p53R273H mutation occurs within RasV12
transformed epithelia, cell death is strongly suppressed and most of the p53R273H
expressing cells remain intact. These results suggest that the order of oncogenic
mutations in cancer development could be dictated by cell competition.
PMID- 29949758
TI - L1 Retrotransposon Heterogeneity in Ovarian Tumor Cell Evolution.
AB - LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor
cells. However, the clinical significance of L1 mobilization during tumorigenesis
remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to
multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa
cells and detected endogenous L1 retrotransposition in vitro. We then applied RC
seq to ovarian tumor and matched blood samples from 19 patients and identified 88
tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion
supplied a novel cis-enhancer to the putative chemoresistance gene STC1. Notably,
the tumor subclone carrying the STC1 L1 mutation increased in prevalence after
chemotherapy, further increasing STC1 expression. We also identified
hypomethylated donor L1s responsible for new L1 insertions in tumors and
cultivated cancer cells. These congruent in vitro and in vivo results highlight
L1 insertional mutagenesis as a common component of ovarian tumorigenesis and
cancer genome heterogeneity.
PMID- 29949759
TI - The PARP1-Siah1 Axis Controls HIV-1 Transcription and Expression of Siah1
Substrates.
AB - Recent studies have revealed a key role of PARP1 that catalyzes the poly-ADP
ribosylation (PARylation) of substrates in regulating gene transcription. We show
here that HIV-1 transcriptional activation also requires PARP1 activity. Because
efficient HIV-1 transactivation is known to depend on the ELL2-containing super
elongation complex (SEC), we investigated the functional relationship between
PARP1 and ELL2-SEC in HIV-1 transcriptional control. We show that PARP1 elevates
ELL2 protein levels to form more ELL2-SEC in cells. This effect is caused by
PARP1's suppression of expression of Siah1, an E3 ubiquitin ligase for ELL2, at
both mRNA and protein levels. At the mRNA level, PARP1 coordinates with the co
repressor NCoR to suppress Siah1 transcription. At the protein level, PARP1
promotes Siah1 proteolysis, likely through inducing PARylation-dependent
ubiquitination (PARdU) of Siah1. Thus, a PARP1-Siah1 axis activates HIV-1
transcription and controls the expression of ELL2 and other Siah1 substrates.
PMID- 29949760
TI - Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated
Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.
AB - The intestinal tract is constantly exposed to various stimuli. Group 3 innate
lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and
are required for immunity to enteric bacterial infection. However, the mechanisms
that regulate the ILC3s in vivo remain incompletely defined. Here, we show that
GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates
ILC3 migration toward its ligand 7alpha,25-dihydroxycholesterol (7alpha,25-OHC)
in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of
ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine.
GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more
susceptible to enteric bacterial infection. Together, these results reveal a role
for the GPR183-7alpha,25-OHC pathway in regulating the accumulation,
distribution, and anti-microbial and tissue-protective functions of ILC3s and
define a critical role for this pathway in promoting innate immunity to enteric
bacterial infection.
PMID- 29949761
TI - NMDA Receptor Autoantibodies in Autoimmune Encephalitis Cause a Subunit-Specific
Nanoscale Redistribution of NMDA Receptors.
AB - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe
neuropsychiatric disorder mediated by autoantibodies against the GluN1 subunit of
the NMDAR. Patients' antibodies cause cross-linking and internalization of NMDAR,
but the synaptic events leading to depletion of NMDAR are poorly understood.
Using super-resolution microscopy, we studied the effects of the autoantibodies
on the nanoscale distribution of NMDAR in cultured neurons. Our findings show
that, under control conditions, NMDARs form nanosized objects and patients'
antibodies increase the clustering of synaptic and extrasynaptic receptors inside
the nano-objects. This clustering is subunit specific and predominantly affects
GluN2B-NMDARs. Following internalization, the remaining surface NMDARs return to
control clustering levels but are preferentially retained at the synapse. Monte
Carlo simulations using a model in which antibodies induce NMDAR cross-linking
and disruption of interactions with other proteins recapitulated these results.
Finally, activation of EphB2 receptor partially antagonized the antibody-mediated
disorganization of the nanoscale surface distribution of NMDARs.
PMID- 29949762
TI - An RNA-Binding Multimer Specifies Nematode Sperm Fate.
AB - FOG-3 is a master regulator of sperm fate in Caenorhabditis elegans and
homologous to Tob/BTG proteins, which in mammals are monomeric adaptors that
recruit enzymes to RNA binding proteins. Here, we determine the FOG-3 crystal
structure and in vitro demonstrate that FOG-3 forms dimers that can multimerize.
The FOG-3 multimeric structure has a basic surface potential, suggestive of
binding nucleic acid. Consistent with that prediction, FOG-3 binds directly to
nearly 1,000 RNAs in nematode spermatogenic germ cells. Most binding is to the 3'
UTR, and most targets (94%) are oogenic mRNAs, even though assayed in
spermatogenic cells. When tethered to a reporter mRNA, FOG-3 represses its
expression. Together these findings elucidate the molecular mechanism of sperm
fate specification and reveal the evolution of a protein from monomeric to
multimeric form with acquisition of a distinct mode of mRNA repression.
PMID- 29949763
TI - MicroRNAs Regulate Sleep and Sleep Homeostasis in Drosophila.
AB - To discover microRNAs that regulate sleep, we performed a genetic screen using a
library of miRNA sponge-expressing flies. We identified 25 miRNAs that regulate
baseline sleep; 17 were sleep-promoting and 8 promoted wake. We identified one
miRNA that is required for recovery sleep after deprivation and 8 miRNAs that
limit the extent of recovery sleep. 65% of the hits belong to human-conserved
families. Interestingly, the majority (75%), but not all, of the baseline sleep
regulating miRNAs are required in neurons. Sponges that target miRNAs in the same
family, including the miR-92a/92b/310 family and the miR-263a/263b family, have
similar effects. Finally, mutation of one of the screen's strongest hits, let-7,
using CRISPR/Cas-9, phenocopies sponge-mediated let-7 inhibition. Cell-type
specific and temporally restricted let-7 sponge expression experiments suggest
that let-7 is required in the mushroom body both during development and in
adulthood. This screen sets the stage for understanding the role of miRNAs in
sleep.
PMID- 29949764
TI - A De Novo Mouse Model of C11orf95-RELA Fusion-Driven Ependymoma Identifies Driver
Functions in Addition to NF-kappaB.
AB - The majority of supratentorial ependymomas (ST-ependymomas) have few mutations
but frequently display chromothripsis of chromosome 11q that generates a fusion
between C11orf95 and RELA (RELAFUS). Neural stem cells transduced with RELAFUSex
vivo form ependymomas when implanted in the brain. These tumors display enhanced
NF-kappaB signaling, suggesting that this aberrant signal is the principal
mechanism of oncogenesis. However, it is not known whether RELAFUS is sufficient
to drive de novo ependymoma tumorigenesis in the brain and, if so, whether these
tumors also arise from neural stem cells. We show that RELAFUS drives ST
ependymoma formation from periventricular neural stem cells in mice and that
RELAFUS-induced tumorigenesis is likely dependent on a series of cell signaling
pathways in addition to NF-kappaB.
PMID- 29949765
TI - TGF-beta Determines the Pro-migratory Potential of bFGF Signaling in
Medulloblastoma.
AB - The microenvironment shapes cell behavior and determines metastatic outcomes of
tumors. We addressed how microenvironmental cues control tumor cell invasion in
pediatric medulloblastoma (MB). We show that bFGF promotes MB tumor cell invasion
through FGF receptor (FGFR) in vitro and that blockade of FGFR represses brain
tissue infiltration in vivo. TGF-beta regulates pro-migratory bFGF function in a
context-dependent manner. Under low bFGF, the non-canonical TGF-beta pathway
causes ROCK activation and cortical translocation of ERK1/2, which antagonizes
FGFR signaling by inactivating FGFR substrate 2 (FRS2), and promotes a
contractile, non-motile phenotype. Under high bFGF, negative-feedback regulation
of FRS2 by bFGF-induced ERK1/2 causes repression of the FGFR pathway. Under these
conditions, TGF-beta counters inactivation of FRS2 and restores pro-migratory
signaling. These findings pinpoint coincidence detection of bFGF and TGF-beta
signaling by FRS2 as a mechanism that controls tumor cell invasion. Thus,
targeting FRS2 represents an emerging strategy to abrogate aberrant FGFR
signaling.
PMID- 29949767
TI - Increased Grik4 Gene Dosage Causes Imbalanced Circuit Output and Human Disease
Related Behaviors.
AB - Altered glutamatergic neurotransmission is thought to contribute to mental
disorders and neurodegenerative diseases. Copy-number variation in genes
associated with glutamatergic synapses represents a source of genetic
variability, possibly underlying neurological and mental disease susceptibility.
The GRIK4 gene encodes a high-affinity kainate receptor subunit of essentially
unknown function, although de novo duplication of the 11q23.3-q24.1 locus to
which it maps has been detected in autism and other disorders. To determine how
changes in the dose of Grik4 affect synaptic activity, we studied mice
overexpressing this gene in the forebrain. A mild gain in Grik4 enhances synaptic
transmission, causing a persistent imbalance in inhibitory and excitatory
activity and disturbing the circuits responsible for the main amygdala outputs.
These changes in glutamatergic activity reverse when Grik4 levels are normalized;
thus, they may account for the behavioral abnormalities in disorders like autism
or schizophrenia.
PMID- 29949766
TI - Inhibition of Lysosome Membrane Recycling Causes Accumulation of Gangliosides
that Contribute to Neurodegeneration.
AB - Lysosome membrane recycling occurs at the end of the autophagic pathway and
requires proteins that are mostly encoded by genes mutated in neurodegenerative
diseases. However, its implication in neuronal death is still unclear. Here, we
show that spatacsin, which is required for lysosome recycling and whose loss of
function leads to hereditary spastic paraplegia 11 (SPG11), promotes clearance of
gangliosides from lysosomes in mouse and human SPG11 models. We demonstrate that
spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome
membrane recycling and clearance of gangliosides from lysosomes. Gangliosides
contributed to the accumulation of autophagy markers in lysosomes and to neuronal
death. In contrast, decreasing ganglioside synthesis prevented neurodegeneration
and improved motor phenotype in a SPG11 zebrafish model. Our work reveals how
inhibition of lysosome membrane recycling leads to the deleterious accumulation
of gangliosides, linking lysosome recycling to neurodegeneration.
PMID- 29949768
TI - NGL-2 Deletion Leads to Autistic-like Behaviors Responsive to NMDAR Modulation.
AB - Netrin-G ligand 2 (NGL-2)/LRRC4, implicated in autism spectrum disorders and
schizophrenia, is a leucine-rich repeat-containing postsynaptic adhesion molecule
that interacts intracellularly with the excitatory postsynaptic scaffolding
protein PSD-95 and trans-synaptically with the presynaptic adhesion molecule
netrin-G2. Functionally, NGL-2 regulates excitatory synapse development and
synaptic transmission. However, whether it regulates synaptic plasticity and
disease-related specific behaviors is not known. Here, we report that mice
lacking NGL-2 (Lrrc4-/- mice) show suppressed N-Methyl-D-aspartate receptor
(NMDAR)-dependent synaptic plasticity in the hippocampus. NGL-2 associates with
NMDARs through both PSD-95-dependent and -independent mechanisms. Moreover, Lrrc4
/- mice display mild social interaction deficits and repetitive behaviors that
are rapidly improved by pharmacological NMDAR activation. These results suggest
that NGL-2 promotes synaptic stabilization of NMDARs, regulates NMDAR-dependent
synaptic plasticity, and prevents autistic-like behaviors from developing in
mice, supporting the hypothesis that NMDAR dysfunction contributes to autism
spectrum disorders.
PMID- 29949770
TI - The Molecular Motor KIF21B Mediates Synaptic Plasticity and Fear Extinction by
Terminating Rac1 Activation.
AB - Fear extinction is a component of cognitive flexibility that is relevant for
important psychiatric diseases, but its molecular mechanism is still largely
elusive. We established mice lacking the kinesin-4 motor KIF21B as a model for
fear extinction defects. Postsynaptic NMDAR-dependent long-term depression (LTD)
is specifically impaired in knockouts. NMDAR-mediated LTD-causing stimuli induce
dynamic association of KIF21B with the Rac1GEF subunit engulfment and cell
motility protein 1 (ELMO1), leading to ELMO1 translocation out of dendritic
spines and its sequestration in endosomes. This process may essentially terminate
transient activation of Rac1, shrink spines, facilitate AMPAR endocytosis, and
reduce postsynaptic strength, thereby forming a mechanistic link to LTD
expression. Antagonizing ELMO1/Dock Rac1GEF activity by the administration of 4
[3'-(2"-chlorophenyl)-2'-propen-1'-ylidene]-1-phenyl-3,5-pyrazolidinedione
(CPYPP) significantly reverses the knockout phenotype. Therefore, we propose that
KIF21B-mediated Rac1 inactivation is a key molecular event in NMDAR-dependent LTD
expression underlying cognitive flexibility in fear extinction.
PMID- 29949769
TI - Cocaine Inhibition of Synaptic Transmission in the Ventral Pallidum Is Pathway
Specific and Mediated by Serotonin.
AB - The ventral pallidum (VP) is part of the basal ganglia circuitry and a target of
both direct and indirect pathway projections from the nucleus accumbens. VP is
important in cocaine reinforcement, and the firing of VP neurons is modulated in
vivo during cocaine self-administration. This modulation of firing is thought to
be indirect via cocaine actions on dopamine in the accumbens. Here, we show that
cocaine directly inhibits synaptic transmission evoked by selective stimulation
of indirect pathway projections to VP neurons. The inhibition is independent of
dopamine receptor activation, absent in 5-HT1B knockout mice, and mimicked by a
serotonin transporter (SERT) blocker. SERT-expressing neurons in dorsal raphe
project to the VP. Optogenetic stimulation of these projections evokes serotonin
transients and effectively inhibits GABAergic transmission to VP neurons. This
study shows that cocaine increases endogenous serotonin in the VP to suppress
synaptic transmission selectively from indirect pathway projections to VP
neurons.
PMID- 29949771
TI - Synchronized Astrocytic Ca2+ Responses in Neurovascular Coupling during
Somatosensory Stimulation and for the Resting State.
AB - The role of astrocytes in neurovascular coupling (NVC) is unclear. Here, we
applied a multimodality imaging approach to concomitantly measure synchronized
neuronal or astrocytic Ca2+ and hemodynamic changes in the mouse somatosensory
cortex at rest and during sensory electrical stimulation. Strikingly, we found
that low-frequency stimulation (0.3-1 Hz), which consistently evokes fast
neuronal Ca2+ transients (6.0 +/- 2.7 ms latency) that always precede vascular
responses, does not always elicit astrocytic Ca2+ transients (313 +/- 65 ms
latency). However, the magnitude of the hemodynamic response is increased when
astrocytic transients occur, suggesting a facilitatory role of astrocytes in NVC.
High-frequency stimulation (5-10 Hz) consistently evokes a large, delayed
astrocytic Ca2+ accumulation (3.48 +/- 0.09 s latency) that is temporarily
associated with vasoconstriction, suggesting a role for astrocytes in resetting
NVC. At rest, neuronal, but not astrocytic, Ca2+ fluctuations correlate with
hemodynamic low-frequency oscillations. Taken together, these results support a
role for astrocytes in modulating, but not triggering, NVC.
PMID- 29949772
TI - Calcium Influx and Release Cooperatively Regulate AChR Patterning and Motor Axon
Outgrowth during Neuromuscular Junction Formation.
AB - Formation of synapses between motor neurons and muscles is initiated by
clustering of acetylcholine receptors (AChRs) in the center of muscle fibers
prior to nerve arrival. This AChR patterning is considered to be critically
dependent on calcium influx through L-type channels (CaV1.1). Using a genetic
approach in mice, we demonstrate here that either the L-type calcium currents
(LTCCs) or sarcoplasmic reticulum (SR) calcium release is necessary and
sufficient to regulate AChR clustering at the onset of neuromuscular junction
(NMJ) development. The combined lack of both calcium signals results in loss of
AChR patterning and excessive nerve branching. In the absence of SR calcium
release, the severity of synapse formation defects inversely correlates with the
magnitude of LTCCs. These findings highlight the importance of activity-dependent
calcium signaling in early neuromuscular junction formation and indicate that
both LTCC and SR calcium release individually support proper innervation of
muscle by regulating AChR patterning and motor axon outgrowth.
PMID- 29949774
TI - Re-evaluating the Localization of Sperm-Retained Histones Revealed the
Modification-Dependent Accumulation in Specific Genome Regions.
AB - The question of whether retained histones in the sperm genome localize to gene
coding regions or gene deserts has been debated for years. Previous contradictory
observations are likely caused by the non-uniform sensitivity of sperm chromatin
to micrococcal nuclease (MNase) digestion. Sperm chromatin has a highly condensed
but heterogeneous structure and is composed of 90%~99% protamines and 1%~10%
histones. In this study, we utilized nucleoplasmin (NPM) to improve the
solubility of sperm chromatin by removing protamines in vitro. NPM treatment
efficiently solubilized histones while maintaining quality and quantity.
Chromatin immunoprecipitation sequencing (ChIP-seq) analyses using NPM-treated
sperm demonstrated the predominant localization of H4 to distal intergenic
regions, whereas modified histones exhibited a modification-dependent
preferential enrichment in specific genomic elements, such as H3K4me3 at CpG-rich
promoters and H3K9me3 in satellite repeats, respectively, implying the existence
of machinery protecting modified histones from eviction.
PMID- 29949773
TI - A PQM-1-Mediated Response Triggers Transcellular Chaperone Signaling and
Regulates Organismal Proteostasis.
AB - In metazoans, tissues experiencing proteotoxic stress induce "transcellular
chaperone signaling" (TCS) that activates molecular chaperones, such as hsp-90,
in distal tissues. How this form of inter-tissue communication is mediated to
upregulate systemic chaperone expression and whether it can be utilized to
protect against protein misfolding diseases remain open questions. Using C.
elegans, we identified key components of a systemic stress signaling pathway that
links the innate immune response with proteostasis maintenance. We show that mild
perturbation of proteostasis in the neurons or the intestine activates TCS via
the GATA zinc-finger transcription factor PQM-1. PQM-1 coordinates neuron
activated TCS via the innate immunity-associated transmembrane protein CLEC-41,
whereas intestine-activated TCS depends on the aspartic protease ASP-12. Both TCS
pathways can induce hsp-90 in muscle cells and facilitate amelioration of Abeta3
42-associated toxicity. This may have powerful implications for the treatment of
diseases related to proteostasis dysfunction.
PMID- 29949775
TI - The Tumor Suppressor ARID1A Controls Global Transcription via Pausing of RNA
Polymerase II.
AB - AT-rich interactive domain-containing proteins 1A and 1B (ARID1A and ARID1B) are
mutually exclusive subunits of the chromatin remodeler SWI/SNF. ARID1A is the
most frequently mutated chromatin regulator across all cancers, and ovarian clear
cell carcinoma (OCCC) carries the highest prevalence of ARID1A mutations (~57%).
Despite evidence implicating ARID1A in tumorigenesis, the mechanism remains
elusive. Here, we demonstrate that ARID1A binds active regulatory elements in
OCCC. Depletion of ARID1A represses RNA polymerase II (RNAPII) transcription but
results in modest changes to accessibility. Specifically, pausing of RNAPII is
severely impaired after loss of ARID1A. Compromised pausing results in
transcriptional dysregulation of active genes, which is compensated by
upregulation of ARID1B. However, a subset of ARID1A-dependent genes is not
rescued by ARID1B, including many p53 and estrogen receptor (ESR1) targets. Our
results provide insight into ARID1A-mediated tumorigenesis and unveil functions
of SWI/SNF in modulating RNAPII dynamics.
PMID- 29949776
TI - Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis.
AB - Destruction of cancer cells by therapeutic antibodies occurs, at least in part,
through antibody-dependent cellular cytotoxicity (ADCC), and this can be mediated
by various Fc-receptor-expressing immune cells, including neutrophils. However,
the mechanism(s) by which neutrophils kill antibody-opsonized cancer cells has
not been established. Here, we demonstrate that neutrophils can exert a mode of
destruction of cancer cells, which involves antibody-mediated trogocytosis by
neutrophils. Intimately associated with this is an active mechanical disruption
of the cancer cell plasma membrane, leading to a lytic (i.e., necrotic) type of
cancer cell death. Furthermore, this mode of destruction of antibody-opsonized
cancer cells by neutrophils is potentiated by CD47-SIRPalpha checkpoint blockade.
Collectively, these findings show that neutrophil ADCC toward cancer cells occurs
by a mechanism of cytotoxicity called trogoptosis, which can be further improved
by targeting CD47-SIRPalpha interactions.
PMID- 29949777
TI - DFR1-Mediated Inhibition of Proline Degradation Pathway Regulates Drought and
Freezing Tolerance in Arabidopsis.
AB - Proline accumulation is one of the most important adaptation mechanisms for
plants to cope with environmental stresses, such as drought and freezing.
However, the molecular mechanism of proline homeostasis under these stresses is
largely unknown. Here, we identified a mitochondrial protein, DFR1, involved in
the inhibition of proline degradation in Arabidopsis. DFR1 was strongly induced
by drought and cold stresses. The dfr1 knockdown mutants showed hypersensitivity
to drought and freezing stresses, whereas the DFR1 overexpression plants
exhibited enhanced tolerance, which was positively correlated with proline
levels. DFR1 interacts with proline degradation enzymes PDH1/2 and P5CDH and
compromises their activities. Genetic analysis showed that DFR1 acts upstream of
PDH1/2 and P5CDH to positively regulate proline accumulation. Our results
demonstrate a regulatory mechanism by which, under drought and freezing stresses,
DFR1 interacts with PDH1/2 and P5CDH to abrogate their activities to maintain
proline homeostasis, thereby conferring drought and freezing tolerance.
PMID- 29949778
TI - Targeting a Sirt5-Positive Subpopulation Overcomes Multidrug Resistance in Wild
Type Kras Colorectal Carcinomas.
PMID- 29949779
TI - Fine-Tuned and Cell-Cycle-Restricted Expression of Fusogenic Protein Syncytin-2
Maintains Functional Placental Syncytia.
PMID- 29949780
TI - Physical and Psychosocial Factors in the Prevention of Chronic Pain in Older Age.
AB - Chronic pain is recognized as a major challenge as people age. Yet, despite
growing research on chronic pain management, there is little research into
chronic pain prevention. Thus there is a clear need to identify multimodal
activities that could be encouraged among older adults as part of a healthy
lifestyle to decrease the incidence risk of chronic pain. Using data from the
English Longitudinal Study of Ageing we tracked 2,631 adults aged >=50 years who
were free from chronic pain at baseline across a decade and explore whether
physical or psychosocial factors reduced the risk of developing chronic pain. In
relation to physical factors, engaging in vigorous weekly activity was protective
against the development of chronic pain (odds ratio 0.74, standard error 0.07,
95% confidence interval 0.62-0.89) when controlling for all identified
socioeconomic, health, and social confounders. However, no effects were found for
moderate weekly activity. In relation to psychosocial factors, cultural
engagement was also protective against the development of chronic pain (odds
ratio 0.75, standard error 0.07, 95% confidence interval 0.63-0.91), but
community group participation was not. These findings extend previous work
showing that physical activity and psychosocial factors such as positive affect
are key factors in the long-term success of chronic pain self-management. Future
interventional studies for chronic pain are encouraged. PERSPECTIVE: This article
explores whether physical and psychosocial activities could reduce the risk of
developing chronic pain in older age. These results could potentially help
clinicians to recommend multimodal activities as part of a broader healthy
lifestyle for those aged >=50 years to reduce the incidence rate of chronic pain.
PMID- 29949781
TI - Omalizumab chronic spontaneous urticaria: Efficacy, safety, predictors of
treatment outcome, and time to response.
AB - BACKGROUND: Omalizumab is a recombinant anti-immunoglobulin E (IgE) antibody used
in the treatment of patients with chronic spontaneous urticaria (CSU). OBJECTIVE:
This multicentric study assessed the safety and efficacy of omalizumab in
patients (n=322) with CSU refractory to second-generation antihistamines, also
investigating predictors of poor treatment outcome and time lag to response to
anti-IgE therapy by serum auto-reactivity. METHODS: This retrospective
observational study comprised a 4-week pretreatment period, a 24-week treatment
period with omalizumab (300 mg/month), and a 16-week follow-up period. Primary
efficacy endpoints were mean and median change in 7-day urticaria activity score
(UAS7), weekly itch severity score (ISS), and hive score from baseline to 4-, 12
, and 24-week values. Secondary endpoints included the proportion of patients
(defined "responders") with well-controlled urticaria (UAS7 <= 6) and complete
treatment response (UAS7=0). Safety in terms of side effects was also assessed.
RESULTS: Omalizumab significantly and consistently reduced the mean UAS7, ISS,
and hive score from baseline to weeks 4, 12, and 24, with a clear decreasing
trend over time. At the end of the treatment period (week 24), 84.2% of patients
had a UAS7 score of 6 or less and 66.7% had a UAS7 of 0. Higher pretreatment IgE
levels were less likely to be associated with poor treatment response (ie, UAS7 >
6). Patients with a positive autologus serum skin test (ASST) were significantly
more likely to be "slow responders" to omalizumab treatment (ie, response beyond
8 days since omalizumab administration) than ASST-negative patients (P < .001).
No treatment-related adverse events were recorded. CONCLUSION: Monitoring
baseline characteristics of patients before introduction of omalizumab therapy
may help to predict treatment outcome in CSU patients.
PMID- 29949782
TI - Erratum.
PMID- 29949783
TI - Effect of P450 Oxidoreductase Polymorphisms on the Metabolic Activities of Ten
Cytochrome P450s Varied by Polymorphic CYP Genotypes in Human Liver Microsomes.
AB - : Background/ Aims: Little is known about the effect of P450 oxidoreductase (POR)
gene polymorphisms on the activities of CYPs with multiple genotypes. METHODS: We
genotyped 102 human livers for 18 known POR single nucleotide polymorphisms
(SNPs) with allelic frequencies greater than 1% as well as for 27 known SNPs in
10 CYPs. CYP enzyme activities in microsomes prepared from these livers were
determined by measuring probe substrate metabolism by high performance liquid
chromatograph. RESULTS: We found that the effects of the 18 POR SNPs on 10 CYP
activities were CYP genotype-dependent. The POR mutations were significantly
associated with decreased overall Km for CYP2B6 and 2E1, and specific genotypes
within CYP1A2, 2A6, 2B6, 2C8, 2D6 and 2E1 were identified as being affected by
these POR SNPs. Notably, the effect of a specific POR mutation on the activity of
a CYP genotype could not be predicted from other CYP genotypes of even the same
CYP. When combining one POR SNP with other POR SNPs, a hitherto unrecognized
effect of multiple-site POR gene polymorphisms (MSGP) on CYP activity was
uncovered, which was not necessarily consistent with the effect of either single
POR SNP. CONCLUSIONS: The effects of POR SNPs on CYP activities were not only CYP
dependent, but more importantly, CYP genotype-dependent. Moreover, the effect of
a POR SNP alone and in combination with other POR SNPs (MSGP) was not always
consistent, nor predictable. Understanding the impact of POR gene polymorphisms
on drug metabolism necessitates knowing the complete SNP complement of POR and
the genotype of the relevant CYPs.
PMID- 29949784
TI - MiR-592 Promotes Gastric Cancer Proliferation, Migration, and Invasion Through
the PI3K/AKT and MAPK/ERK Signaling Pathways by Targeting Spry2.
AB - BACKGROUND/AIMS: Gastric cancer (GC) is one of the most prevalent digestive
malignancies. MicroRNAs (miRNAs) are involved in multiple cellular processes,
including oncogenesis, and miR-592 itself participates in many malignancies;
however, its role in GC remains unknown. In this study, we investigated the
expression and molecular mechanisms of miR-592 in GC. METHODS: Quantitative real
time PCR and immunohistochemistry were performed to determine the expression of
miR-592 and its putative targets in human tissues and cell lines. Proliferation,
migration, and invasion were evaluated by Cell Counting Kit-8, population
doubling time, colony formation, Transwell, and wound-healing assays in
transfected GC cells in vitro. A dual-luciferase reporter assay was used to
determine whether miR-592 could directly bind its target. A tumorigenesis assay
was used to study whether miR-592 affected GC growth in vivo. Proteins involved
in signaling pathways and the epithelial-mesenchymal transition (EMT) were
detected with western blot. RESULTS: The ectopic expression of miR-592 promoted
GC proliferation, migration, and invasion in vitro and facilitated tumorigenesis
in vivo. Spry2 was a direct target of miR-592 and Spry2 overexpression partially
counteracted the effects of miR-592. miR-592 induced the EMT and promoted its
progression in GC via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting
Spry2. CONCLUSIONS: Overexpression of miR-592 promotes GC proliferation,
migration, and invasion and induces the EMT via the PI3K/AKT and MAPK/ERK
signaling pathways by inhibiting Spry2, suggesting a potential therapeutic target
for GC.
PMID- 29949785
TI - Identification of Carbonic Anhydrase IX as a Novel Target for Endoscopic
Molecular Imaging of Human Bladder Cancer.
AB - BACKGROUND/AIMS: Emerging novel optical imaging techniques with cancer-specific
molecular imaging agents offer a powerful and promising platform for cancer
detection and resection. White-light cystoscopy and random bladder biopsies
remain the most appropriate but nonetheless suboptimal diagnostic technique for
bladder cancer, which is associated with high morbidity and recurrence. However,
white-light cystoscopy has intrinsic shortcomings. Although current optical
imaging technologies hold great potential for improved diagnostic accuracy, there
are few imaging agents for specific molecular targeting. Carbonic anhydrase IX
(CAIX) plays a pivotal role in tumorigenesis and tumor progression with potential
value as an imaging target. Here, we investigated the feasibility of CAIX as a
target and validated the diagnostic performance and significance of CAIX as an
imaging agent. METHODS: We first analyzed the data from The Cancer Genome Atlas
(TCGA). Pairs of samples comprising bladder cancer and adjacent normal tissue
were collected. All tissue samples were used for real-time PCR and
immunohistochemistry to compare CAIX expression in normal and cancer tissue.
Using blue-light cystoscopy, we observed the optical distribution of
fluorescently labeled CAIX antibody in freshly excised human bladders and
obtained random bladder biopsies to assess sensitivity and specificity. RESULTS:
The TCGA data revealed that CAIX expression was significantly higher in bladder
cancer specimens than in normal tissue. The outcome was similar in quantitative
real-time PCR analysis. In immunohistochemical analysis, bladder cancer specimens
classified in four pathological subtypes presented a variety of positive staining
intensities, whereas no benign specimens showed CAIX staining. Using blue-light
cystoscopy, we distinguished bladder cancers that were mainly papillary, some
variants of urothelial carcinoma, and less carcinoma in situ, from benign tissue,
despite the presence of suspicious-appearing mucosa. The sensitivity and
specificity for CAIX-targeted imaging were 88.00% and 93.75%, respectively.
CONCLUSIONS: CAIX-targeted molecular imaging could be a feasible and adaptive
alternative approach for the accurate diagnosis and complete resection of bladder
cancer.
PMID- 29949786
TI - Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human
Laryngeal Squamous Cell Carcinoma Cells.
AB - BACKGROUND/AIMS: CD133+CD44+ cancer stem cells previously isolated from laryngeal
squamous cell carcinoma (LSCC) cell lines showed strong malignancy and
tumorigenicity. However, the molecular mechanism underlying the enhanced
malignancy remained unclear. METHODS: Cell proliferation assay, spheroid
formation experiment, RNA sequencing (RNA-seq), miRNA-seq, bioinformatic
analysis, quantitative real-time PCR, migration assay, invasion assay, and
luciferase reporter assay were used to identify differentially expressed mRNAs,
lncRNAs, circRNAs and miRNAs, construct transcription regulatory network, and
investigate functional roles and mechanism of circRNA in CD133+CD44+ laryngeal
cancer stem cells. RESULTS: Differentially expressed genes in TDP cells were
mainly enriched in the biological processes of cell differentiation, regulation
of autophagy, negative regulation of cell death, regulation of cell growth,
response to hypoxia, telomere maintenance, cellular response to gamma radiation,
and regulation of apoptotic signaling, which are closely related to the malignant
features of tumor cells. We constructed the regulatory network of differentially
expressed circRNAs, miRNAs and mRNAs. qPCR findings for the expression of key
genes in the network were consistent with the sequencing data. Moreover, our data
revealed that circRNA hg19_circ_0005033 promotes proliferation, migration,
invasion, and chemotherapy resistance of laryngeal cancer stem cells.
CONCLUSIONS: This study provides potential biomarkers and targets for LSCC
diagnosis and therapy, and provide important evidences for the heterogeneity of
LSCC cells at the transcription level.
PMID- 29949787
TI - MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by
Directly Targeting Rictor.
AB - BACKGROUND/AIMS: Atherosclerosis, a multifactorial chronic disease, is the main
cause of death and impairment in the world. Endothelial cells (ECs) apoptosis
plays a crucial role in the onset and development of atherosclerosis, whereas the
underlying molecular mechanisms are unclear. MicroRNA-142-3p (miR-142-3p) is a
well-defined tumor suppressor in several types of cancer, while the role of miR
142-3p in ECs apoptosis and the development of atherosclerosis has yet to be
elucidated. Therefore, the present study aimed to investigate the role of miR-142
3p in ECs apoptosis during atherosclerosis and the underlying mechanism. METHODS:
Human aortic endothelial cells (HAECs) were treated with oxidized low-density
lipoprotein (ox-LDL). The expression level of miR-142-3p was detected using qRT
PCR. Apoptosis was determined via flow cytometry and Caspase-3 activity assay.
Prediction of the binding between miR-142-3p and 3'-UTR of Rictor mRNA was
performed by bioinformatics analyses and confirmed by a dual luciferase reporter
assay. The effects of miR-142-3p on endothelial apoptosis and atherosclerosis
were further analyzed in an in vivo model using ApoE-/- mice fed with high-fat
diet (HFD). RESULTS: MiR-142-3p expression was substantially up-regulated during
the ox-LDL-elicited apoptosis in HAECs. Forced expression of miR-142-3p
exacerbated apoptosis in ECs whereas inhibition of miR-142-3p could partly
alleviate apoptotic cell death mediated by ox-LDL. Further analysis identified
Rictor as a direct target of miR-142-3p, and Rictor knockdown abolished the anti
apoptotic effect of miR-142-3p inhibitor. Moreover, the Akt/endothelial nitric
oxide synthase (eNOS) signaling pathway was found to mediate the beneficial
effect of miR-142-3p inhibitor on endothelial apoptosis. Finally, systemic
treatment with miR-142-3p antagomir attenuated endothelial apoptosis and retarded
the progression of atherosclerosis in the aorta of ApoE-/- mice. CONCLUSIONS:
Down-regulation of miR-142-3p inhibited ECs apoptosis and atherosclerotic
development by up-regulating the expression of Rictor and activating the Akt/eNOS
signaling pathway. This indicates that miR-142-3p may be a potential target for
the prevention and treatment of atherosclerosis.
PMID- 29949788
TI - MicroRNA-142 Inhibits Proliferation and Promotes Apoptosis in Airway Smooth
Muscle Cells During Airway Remodeling in Asthmatic Rats via the Inhibition of TGF
beta -Dependent EGFR Signaling Pathway.
AB - BACKGROUND/AIMS: Asthma is a heterogeneous disease characterized by chronic
airway inflammation resulting from airway hyper-responsiveness to diverse
stimuli. In this study, we investigated whether microRNA-142 (miR-142) expression
affects proliferation and apoptosis in airway smooth muscle cells (ASMCs) during
airway remodeling in asthmatic rats. METHODS: Thirty six Wistar rats were
randomly classified into a control group and an model group. miR-142 mimics and
inhibitors were constructed, and ASMCs were transfected using liposomes according
to the following groups: blank, negative control (NC), miR-142 mimics, miR-142
inhibitors, si-TGF-beta and miR-142 inhibitors + si-TGF-beta. We verified that
miR-142 targets TGF-beta using a dual-luciferase reporter assay. The expression
levels of miR-142, TGF-beta, EGFR and apoptosis signaling pathway-related genes
were determined using RT-qPCR and western blotting. Changes in cell
proliferation, cell cycle progression and apoptosis were analyzed using MTT
assays and flow cytometry. RESULTS: Rats with asthma had higher expression levels
of EGFR and Akt and lower miR-142 levels. miR-142 was negatively correlated with
TGF-beta expression. In ASMCs, the expression of TGF-beta, EGFR, Akt,
phosphorylated-Akt (p-Akt), Bcl-2 and Bcl-xl and the rate of early apoptosis were
decreased while expression of Bax and p21 and the proliferation rate were
elevated with the upregulation of miR-142. The opposite results were observed
with the downregulation of miR-142. Finally, the proliferative rate was decreased
while the apoptosis rate was increased and expression levels of EGFR, Akt, p-Akt,
Bcl-2 and Bcl-xl were reduced while Bax and p21 were elevated in the ASMCs
transfected with miR-142 inhibitors and si-TGF-beta. CONCLUSION: The results of
our study suggest that miR-142 inhibits proliferation and promotes apoptosis in
ASMCs during airway remodeling in asthmatic rats by inhibiting TGF-beta
expression via a mechanism involving the EGFR signaling pathway.
PMID- 29949789
TI - Pathway Analysis Hints Towards Beneficial Effects of Long-Term Vibration on Human
Chondrocytes.
AB - BACKGROUND/AIMS: Spaceflight negatively influences the function of cartilage
tissue in vivo. In vitro human chondrocytes exhibit an altered gene expression of
inflammation markers after a two-hour exposure to vibration. Little is known
about the impact of long-term vibration on chondrocytes. METHODS: Human cartilage
cells were exposed for up to 24 h (VIB) on a specialised vibration platform
(Vibraplex) simulating the vibration profile which occurs during parabolic
flights and compared to static control conditions (CON). Afterwards, they were
investigated by phase-contrast microscopy, rhodamine phalloidin staining,
microarray analysis, qPCR and western blot analysis. RESULTS: Morphological
investigations revealed no changes between CON and VIB chondrocytes. F-Actin
staining showed no alterations of the cytoskeleton in VIB compared with CON
cells. DAPI and TUNEL staining did not identify apoptotic cells. ICAM-1 was
elevated and vimentin, beta-tubulin and osteopontin proteins were significantly
reduced in VIB compared to CON cells. qPCR of cytoskeletal genes, ITGB1, SOX3,
SOX5, SOX9 did not reveal differential regulations. Microarray analysis detected
13 differentially expressed genes, mostly indicating unspecific stimulations.
Pathway analyses demonstrated interactions of PSMD4 and CNOT7 with ICAM.
CONCLUSIONS: Long-term vibration did not damage human chondrocytes in vitro. The
reduction of osteopontin protein and the down-regulation of PSMD4 and TBX15 gene
expression suggest that in vitro long-term vibration might even positively
influence cultured chondrocytes.
PMID- 29949790
TI - OCT1-Mediated Metformin Uptake Regulates Pancreatic Stellate Cell Activity.
AB - BACKGROUND/AIMS: Metformin treatment is reported to be associated with a lower
incidence of and mortality from pancreatic cancer (PC) in type 2 diabetes
patients. Activated pancreatic stellate cells (PSCs) are key stroma cells
responsible for pancreatic fibrogenesis and PC progression. However, little
research is about the influence of metformin on PSCs. Given the potential
beneficial effects of metformin on PC, pancreatic tumour stroma is an important
target for new therapeutics. We observed the effects of metformin on PSCs. We
investigated the effects of metformin on human PSCs proliferation and the
production of extracellular matrix (ECM) proteins. METHODS: Cells were cultured
with different concentrations of metformin (0-10 mmol/L). Cell proliferation was
determined by immunofluorescence staining for nuclear Ki67 labelling. ECM
production was studied by quantitative real-time polymerase chain reaction,
immunoblotting and immunofluorescence microscopy. Adenosine monophosphate
activated protein kinase (AMPK), an important regulatory molecule responsible for
metformin action, and the organic cation transporter member 1 (OCT1), which is
believed to be the most important transporter for the pharmacological action of
metformin, were investigated for their possible involvements in metformin-induced
proliferation and ECM production. RESULTS: Our results showed that metformin
inhibited PSCs proliferation and decreased the production of ECM proteins by
activation of AMPK phosphorylation. Silencing of OCT1 expression resulted in a
reduction in the effects of metformin on PSCs activity. CONCLUSIONS:
Collectively, the data indicate that OCT1 may contribute to uptake metformin and
regulate PSCs activity. OCT1 is a target of metformin in regulating PSCs
activity.
PMID- 29949791
TI - LncRNA PCGEM1 Induces Ovarian Carcinoma Tumorigenesis and Progression Through
RhoA Pathway.
AB - BACKGROUND/AIMS: Prostate cancer gene expression marker 1 (PCGEM1) is a long
noncoding RNA (lncRNA) and is well known as a promoter in prostate cancer and
osteoarthritis synoviocytes. However, the role PCGEM1 plays in epithelial ovarian
cancer is unknown. METHODS: PCGEM1 expression was examined in epithelial ovarian
cancer and normal ovarian tissues using reverse transcription-PCR. Ovarian cancer
cell phenotypes and genotypes were examined after PCGEM1 overexpression or
downregulation in vitro; besides, the effects of PCGEM1 overexpression was also
examined in vivo. RESULTS: PCGEM1 expression level was higher in epithelial
ovarian cancer tissues than in normal ovarian tissues and was positively
associated with differentiation (Well vs. Mod/Poor). Upregulation of PCGEM1
induced cancer cell proliferation, migration, and invasion, but decreased cell
apoptosis through upregulating RhoA, YAP (Yes-associated protein), MMP2 (matrix
metalloproteinase 2), Bcl-xL, and P70S6K expression; while PCGEM1 downregulation
had the opposite effect. The nude mouse xenograft assay demonstrated that PCGEM1
overexpression promoted tumor growth. Furthermore, silencing RhoA expression
reversed the effect of PCGEM1 and significantly inhibited RhoA, YAP, MMP2, Bcl
xL, and P70S6K protein expression. CONCLUSION: In conclusion, we suggest that
PCGEM1 may be an inducer in epithelial ovarian cancer tumorigenesis and
progression by upregulating RhoA and the subsequent expression of YAP, P70S6K,
MMP2, and Bcl-xL.
PMID- 29949792
TI - Genome-Wide Identification of Circular RNAs as a Novel Class of Putative
Biomarkers for an Ocular Surface Disease.
AB - BACKGROUND/AIMS: Pterygium is a common ocular surface disease with an unknown
etiology and threatens vision as it invades into the cornea. Circular RNAs
(circRNAs) are a novel class of RNA transcripts that participate in several
physiological and pathological processes. However, the role of circRNAs in
pathogenesis of pterygium remains largely unknown. METHODS: Genome-wide circRNA
expression profiling was performed to identify pterygium -related circRNAs. GO
analysis, pathway analysis, and miRNA response elements analysis was performed to
predict the function of differentially expressed circRNAs in pterygium. MTT
assays, Ki67 staining, Transwell assay, Hoechst 33342 staining, and Calcein-AM/PI
staining were performed to determine the effect of circRNA silencing on pterygium
fibroblast and epithelial cell function. RESULTS: Approximately 669 circRNAs were
identified to be abnormally expressed in pterygium tissues. GO analysis
demonstrated that the host genes of differentially expressed circRNAs were
targeted to extracellular matrix organization (ontology: biological process),
cytoplasm (ontology: cellular component), and protein binding (ontology:
molecular function). Pathway analysis showed that dysregulated circRNAs-mediated
regulatory networks were mostly enriched in focal adhesion signaling pathway.
Notably, circ_0085020 (circ-LAPTM4B) was shown as a potential biomarker for
pterygium. circ_0085020 (circ-LAPTM4B) silencing affected the viability,
proliferation, migration, and apoptosis of pterygium fibroblast and epithelial
cells in vitro. CONCLUSIONS: This study provides evidence that circRNAs are
involved in the pathogenesis of pterygium and might constitute promising targets
for the therapeutic intervention of pterygium.
PMID- 29949793
TI - Supplementation of Vitamin E Protects Chickens from Newcastle Disease Virus
Mediated Exacerbation of Intestinal Oxidative Stress and Tissue Damage.
AB - BACKGROUND/AIMS: Newcastle disease virus (NDV) causes a highly devastating and
contagious disease in poultry, which is mainly attributed to extensive tissue
damages in the digestive, respiratory and nervous systems. However, nature and
dynamics of NDV-induced oxidative stresses in the intestine of chickens remain
elusive. METHODS: In this study, we examined the magnitude of intestinal
oxidative stress and histopathological changes caused by the virulent NDV
infection, and explored the protective roles of vitamin E (vit. E) in
ameliorating these pathological changes. For these purposes, chickens were
divided into four groups namely i) non supplemented and non-challenged (negative
control, CON); ii) no supplementation of vit. E but challenged with ZJ1 (positive
control, NS+CHA); iii) vit. E supplementation at the dose of 50 IU/day/Kg body
weight and ZJ1 challenge (VE50+CHA); and 4) vit. E supplementation at the dose of
100 IU/day/Kg body weight and ZJ1 challenge (VE100+CHA). In all groups, we
analyzed concentrations of glutathione (GSH), malondialdehyde (MDA), nitric oxide
(NO), total antioxidant capacity (T-AOC), and activity of glutathione S
transferase (GST), superoxide dismutase (SOD), catalase (CAT) using biochemical
methods. The virus loads were determined by quantitative RT-PCR and antibody
titers by hemagglutination inhibition assays. We also examined the
histopathological changes in the duodenal and jejunal mucosa at 3 and 5-day post
infection (dpi) with NDV. RESULTS: A significant elevation in the NO level was
observed in NDV challenged chickens compared to the CON chickens at 2 dpi. The
MDA contents were significantly increased whereas GSH was significantly decreased
in NDV-challenged chickens compared to control. Furthermore, activities of GST,
CAT, SOD, as well as the TOAC were markedly decreased in challenged chickens in
comparison with control. Virus copy numbers were higher in NDV infected NS+CHA
group compared to other groups. Severe histopathological changes including
inflammation, degeneration and broken villi were observed in the intestine of NDV
challenged chickens. However, all these malfunctions of antioxidant system and
pathological changes in the intestine were partially or completely reversed by
the vit. E supplementation. CONCLUSIONS: Our results suggest that NDV infection
causes oxidative stress and histopathological changes in the duodenum and jejunum
of chickens, which can be partially or fully ameliorated by supplementation of
vit. E. Additionally, these findings suggest that oxidative stress contributes to
the intestinal damages in NDV infected chickens. These findings will help to
understand the pathogenesis of NDV and further investigation of therapeutic
agents for control of Newcastle disease.
PMID- 29949794
TI - Genistein Enhances or Reduces Glycosaminoglycan Quantity in a Cell Type-Specific
Manner.
AB - BACKGROUND/AIMS: Genistein is a natural isoflavone enriched in soybeans. It has
beneficial effects for patients with mucopolysaccharidose type III through
inhibiting glycosaminoglycan biosynthesis. However, other studies indicate that
genistein does not always inhibit glycosaminoglycan biosynthesis. METHODS: To
understand the underlying molecular mechanisms, CHOK1, CHO3.1, CHO3.3, and HCT116
cells were treated with genistein and the monosaccharide compositions and
quantity of all glycans from the cell lysate were measured after thorough acid
hydrolysis followed by HPLC analysis. In addition, the glycosaminoglycan
disaccharide compositions were obtained by stable isotope labeling coupled with
LC/MS analysis. RESULTS: Genistein treatment reduced the amount of glycans but
increased the amount of glycosaminoglycans in HCT116 cells. In contrast,
genistein treatment reduced both glycan and glycosaminoglycan quantities in
CHOK1, CHO3.1, and CHO3.3 cells in addition to differential changes in
glycosaminoglycan disaccharide compositions. CONCLUSION: Genistein treatment
reduced overall glycan quantity but glycosaminoglycan quantities were either
increased or decreased in a cell type-dependent manner.
PMID- 29949796
TI - SIREV-OFTARED Joined Congress Abstracts.
PMID- 29949795
TI - Sodium Butyrate Attenuates Diarrhea in Weaned Piglets and Promotes Tight Junction
Protein Expression in Colon in a GPR109A-Dependent Manner.
AB - BACKGROUND/AIMS: Butyric acid plays an important role in maintaining intestinal
health. Butyric acid has received special attention as a short-chain fatty acid,
but its role in protecting the intestinal barrier is poorly characterized.
Butyric acid not only provides energy for epithelial cells but also acts as a
histone deacetylase inhibitor; it is also a natural ligand for G protein-coupled
receptor 109A (GPR109A). A GPR109A analog was expressed in Sus scrofa and
mediated the anti-inflammatory effects of beta-hydroxybutyric acid. This study
investigated the effects of butyrate on growth performance, diarrhea symptoms,
and tight junction protein levels in 21-day-old weaned piglets. We also studied
the mechanism by which butyric acid regulates intestinal permeability. METHODS:
Twenty-four piglets that had been weaned at an age of 21 days were divided
randomly into 2 equal groups: basal diet group and sodium butyrate + basal diet
group. Diarrhea rate, growth performance during 3 weeks of feeding on these diets
were observed, the lactulose-mannitol ratio in urine were detected by High
Performance Liquid Chromatography, the expression levels of tight junction
proteins in the intestinal tract and related signaling molecules, such as GPR109A
and Akt, in the colon were examined by quantitative real-time PCR or western blot
analyses on day 21. Caco-2 cells were used as a colon cell model and cultured
with or without sodium butyrate to assess the expression of tight junction
proteins and the activation of related signaling molecules. GPR109A-short hairpin
RNA (shRNA) and specific antagonists of Akt and ERK1/2 were used as signaling
pathway inhibitors to elucidate the mechanism by which butyric acid regulates the
expression of tight junction proteins and the colonic epithelial barrier.
RESULTS: The sodium butyrate diet alleviated diarrhea symptoms and decreased
intestinal permeability without affecting the growth of early weaned piglets. The
expression levels of the tight junction proteins Claudin-3, Occludin, and zonula
occludens 1 were up-regulated by sodium butyrate in the colon and Caco-2 cells.
GPR109A knockdown using shRNA or blockade of the Akt signaling pathway in Caco-2
cells suppressed sodium butyrate-induced Claudin-3 expression. CONCLUSIONS:
Sodium butyrate acts on the Akt signaling pathway to facilitate Claudin-3
expression in the colon in a GPR109A-dependent manner.
PMID- 29949798
TI - Long-Term Immune Alterations Accompanying Chronic Posttraumatic Stress Disorder
following Exposure to Suicide Bomb Terror Incidents during Childhood.
AB - BACKGROUND AND AIM: Long-term immune alterations have been proposed to play a
mechanistic role in posttraumatic stress disorder (PTSD) as well as in its
associated increase in medical morbidity and mortality. Better characterization
of altered immune function may help identify diagnostic and prognostic biomarkers
and potentially targets for preventive intervention. METHODS: As part of an
ongoing study, we conducted a preliminary case-control comparison of resting
immune inflammatory profiles between terror victims treated in childhood at the
emergency department over the previous decade, who developed chronic PTSD upon
long-term follow-up, and healthy controls. RESULTS: Our preliminary results in a
subsample of this ongoing study support and extend elevated resting levels of
granulocyte colony-stimulating factor, interleukin-4, and regulated on
activation, normal T cell expressed and secreted in childhood onset chronic PTSD.
CONCLUSION: Chronic immune alterations may participate in inflammatory activation
and signal to the CNS through the neurovascular unit, as well as modulate the
neuroendocrine axis. Better characterization and understanding of these
preliminary findings may point to diagnostic and prognostic biomarkers and
potentially elucidate mechanistic involvement of immune activation in PTSD.
PMID- 29949797
TI - The Role of Progesterone in Feto-Maternal Immunological Cross Talk.
AB - This review aims to provide a brief historical overview of the feto-maternal
immunological relationship, which profoundly influences the outcome of pregnancy.
The initial question posed in the 1950s by Medawar [Symp Soc Exp Biol. 1953; 7:
320-338] was based on the assumption that the maternal immune system recognizes
the fetus as an allograft. Indeed, based on the association between HLA-matching
and spontaneous miscarriage, it became obvious that immunological recognition of
pregnancy is required for a successful gestation. The restricted expression of
polymorphic HLA antigens on the trophoblast, together with the presence of
nonpolymorphic MHC products, excludes recognition by both T and NK cells of
trophoblast-presented antigens; however, gammadelta T cells, which constitute the
majority of decidual T cells, are likely candidates. Indeed, a high number of
activated, progesterone receptor-expressing gammadelta T cells are present in the
peripheral blood of healthy pregnant women and, in the presence of progesterone,
these cells secrete an immunomodulatory protein called progesterone-induced
blocking factor (PIBF). As early as in the peri-implantation period, the embryo
communicates with the maternal immune system via PIBF containing extracellular
vesicles. PIBF contributes to the dominance of Th2-type reactivity which
characterizes normal pregnancy by inducing increased production of Th2 cytokines.
The high expression of this molecule in the decidua might be one of the reasons
for the low cytotoxic activity of decidual NK cells.
PMID- 29949799
TI - A Novel Synonymous Variant in the AVP Gene Associated with Autosomal Dominant
Familial Neurohypophyseal Diabetes Insipidus Causes Partial RNA Missplicing.
AB - OBJECTIVE: Autosomal dominant familial neurohypophyseal diabetes insipidus
(adFNDI) is characterized by severe polyuria and polydipsia and is caused by
variations in the gene encoding the AVP prohormone. This study aimed to ascertain
a correct diagnosis, to identify the underlying genetic cause of adFNDI in a
Swedish family, and to test the hypothesis that the identified synonymous exonic
variant in the AVP gene (c.324G>A) causes missplicing and endoplasmic reticulum
(ER) retention of the prohormone. DESIGN/PATIENTS: Three affected family members
were admitted for fluid deprivation test and dDAVP (1-deamino-8-d-arginine
vasopressin) challenge test. Direct sequencing of the AVP gene was performed in
the affected subjects, and genotyping of the identified variant was performed in
family members. The variant was examined by expression of AVP minigenes
containing the entire coding regions as well as intron 2 of AVP. METHODS/RESULTS:
Clinical tests revealed significant phenotypical variation with both complete and
partial adFNDI phenotype. DNA analysis revealed a synonymous c.324G>A
substitution in one allele of the AVP gene in affected family members only.
Cellular studies revealed both normally spliced and misspliced pre-mRNA in cells
transfected with the AVP c.324G>A minigene. Confocal laser scanning microscopy
showed collective localization of the variant prohormone to ER and vesicular
structures at the tip of cellular processes. CONCLUSION: We identified a
synonymous variant affecting the second nucleotide of exon 3 in the AVP gene
(c.324G>A) in a family in which adFNDI segregates. Notably, we showed that this
variant causes partial missplicing of pre-mRNA, resulting in accumulation of the
variant prohormone in ER. Our study suggests that even a small amount of aberrant
mRNA might be sufficient to disturb cellular function, resulting in adFNDI.
PMID- 29949800
TI - Distribution of Collagen I, III, and IV and Laminin in the Human Liver during
Prenatal Development.
AB - In the absence of systematized data on the extracellular matrix components during
prenatal liver development, the present study aimed to investigate the time of
appearance and distribution of collagen types I, III, and IV and laminin. The
study material included embryonic and fetal livers, aged 7-37 weeks, categorized
into 3 trimesters. The material was stained using hematoxylin-eosin and
immunohistochemistry methods for the identification of collagen I, III, and IV
and laminin. Collagen I was detected near the end of the first trimester in the
capsules and walls of interlobular veins. As the liver matures, collagen I is
increasingly abundant in the capsules, portal area connective tissues, arterial
walls, interlobular veins, sinusoids, and central veins. Collagen III and
collagen IV appear in the middle of the first trimester in the capsules, portal
areas, and walls of central veins, as well as the sinusoids particularly. In
trimesters 2 and 3, these collagens are increasingly present in all the
structures, but collagen IV is also present in nerve fibers. Laminin is
sporadically present adjacent to the sinusoids in trimester 1, while in
trimesters 2 and 3 this protein commonly appears in the walls of arteries and
interlobular veins, in the basal membrane of bile ducts, and in nerve fibers. The
contents of collagen I, III, and IV increase during prenatal development in the
liver capsule, arterial and vein walls, sinusoids, and portal area. Laminin
expression is consistent with that of the collagens with the exception that,
within lobules, laminin disappears with liver maturation.
PMID- 29949801
TI - The Role of YKL-40 in Predicting Resistance to Docetaxel Chemotherapy in Prostate
Cancer.
AB - INTRODUCTION: High baseline YKL-40 serum levels are associated with drug
resistance in several solid tumours. However, their role in predicting docetaxel
(DOC) resistance in prostate cancer (PCa) is unknown. METHODS: Pre-treatment
serum levels of YKL-40 and prostate-specific antigen (PSA) were analyzed in 109
castration-resistant prostate cancer patients who underwent DOC-therapy.
Responsive patients were retreated by repeated series of DOC. Results were
compared with the clinical parameters as well as overall (OS) and disease
specific survival (DSS). RESULTS: YKL-40 but not PSA serum levels were
significantly higher in patients with baseline resistance to DOC (p = 0.035).
Higher YKL-40 and PSA levels were detected in patients with bone metastasis (p =
0.032; p = 0.010) and in those who were not pre-treated with radical
prostatectomy (p = 0.011, p = 0.008). High YKL-40 levels were associated with
shorter OS (p = 0.037) and DSS (p = 0.017) in patients who received DOC in the
first-line setting. In multivariable analysis, ECOG performance status (p =
0.009), presence of any metastases (p = 0.016) and high PSA levels (p = 0.005)
remained independent predictors for DSS. CONCLUSIONS: YKL-40 may help to identify
patients with baseline resistance to DOC and therefore may help to optimize
treatment decisions. In accordance, high pre-treatment YKL-40 serum levels were
associated with shorter OS and DSS in patients who received DOC as first-line
therapy.
PMID- 29949802
TI - Differential Regulation of Cell Proliferation and Apoptosis by Melatonin Receptor
Subtype-Signaling in the Adult Murine Brain.
AB - BACKGROUND/AIMS: Zeitgeber time (ZT)-dependent changes in cell proliferation and
apoptosis are regulated by melatonin receptor (MT)-mediated signaling in the
adult hippocampus and hypothalamic-hypophyseal system. There are two G-protein
coupled MT subtypes, MT1 and MT2. Therefore, the present study examined which MT
subtype is required for the regulation of ZT-dependent changes in cell
proliferation and/or apoptosis in the adult murine brain and pituitary. METHODS:
Adult melatonin-proficient (C3H) mice with targeted deletion of MT1 (MT1 KO) or
MT2 (MT2 KO) were adapted to a 12-h light/12-h dark photoperiod and sacrificed at
ZT00, ZT06, ZT12, and ZT18. Immunohistochemistry for Ki67 or activated caspase-3
served to quantify proliferating and apoptotic cells in the hippocampal
subgranular zone (SGZ) and granule cell layer, the hypothalamic median eminence
(ME), and the hypophyseal pars tuberalis. RESULTS: ZT-dependent changes in cell
proliferation were found exclusively in the SGZ and ME of MT1 KO mice, while
apoptosis showed no ZT-dependent changes in the regions analyzed, neither in MT1
nor in MT2 KO mice. Comparison with our previous studies in C3H mice with
functional MTs and MT1/2 KO mice revealed that MT2-mediated signaling is required
and sufficient for ZT-dependent changes in cell proliferation in the SGZ and ME,
while ZT-dependent changes in apoptosis require signaling from both MT subtypes.
CONCLUSIONS: Our results indicate that generation and timing of ZT-dependent
changes in cell proliferation and apoptosis by melatonin require different MT
subtype constellations and emphasize the importance to shed light on the specific
function of each receptor subtype in different tissues and physiological
conditions.
PMID- 29949804
TI - The 72Pro Variant of the Tumor Protein 53 Is Associated with an Increased Breast
Cancer Risk in the Moroccan Population.
AB - BACKGROUND: The purpose of our case control study is to explore the potential
association of tumor protein 53 (TP53) c.215G>C, p. (Arg72Pro) polymorphism
(rs1042522) with the risk of breast cancer (BC) development in the Moroccan
population. METHODS AND RESULTS: The study population consisted of 125 female
patients with confirmed BC and 126 healthy controls. DNA samples were genotyped
by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism assay
method using BstUI restriction enzyme. We showed that the homozygous genotype of
TP53 72Pro variant was significantly associated with increased BC risk (OR 2.2,
95% CI 1.07-4.54, p = 0.03). The dominant and additive models of TP53 Pro allele
were also correlated to the risk of BC (OR 2.13, 95% CI 1.07-4.23, p = 0.02 and
OR 1.49, 95% CI 1.03-2.16, p = 0.03, respectively). Furthermore, the TP53 Arg72
variant was associated with protection against BC, either in the homozygous
genotype, the dominant or the additive models (OR 0.45, 95% CI 0.22-0.93, p =
0.03; OR 0.46, 95% CI 0.23-0.92, p = 0.029 and OR 0.67, 95% CI 0.46-0.97, p =
0.03, respectively). CONCLUSION: Our results suggest that TP53 c.215G>C, p.
(Arg72Pro) polymorphism may be considered as a genetic marker for predisposition
to BC in Moroccan population.
PMID- 29949803
TI - Comparison of Preterm and Term Wharton's Jelly-Derived Mesenchymal Stem Cell
Properties in Different Oxygen Tensions.
AB - Mesenchymal stem cells (MSCs) have shown promise as therapeutic agents in
treating morbidities associated with premature birth. MSCs derived from the human
umbilical cord are easy to isolate and have low immunogenicity and a robust
ability to secrete paracrine factors. To date, there are no studies evaluating
preterm versus term umbilical cord tissue-derived MSCs. Therefore, our aim was
twofold: (1) to compare stem cell properties in preterm versus term MSCs and (2)
to examine the impact of oxygen tension on stem cell behavior. Umbilical cord
tissue was obtained from 5 preterm and 5 term neonates. The cells were isolated
and characterized as MSCs in accordance with the International Society for
Cellular Therapy. We exposed MSCs to different oxygen tensions to examine the
impact of environmental factors on cell performance. We studied the following
stem cell properties: (i) motility, (ii) proliferation, (iii) senescence, (iv)
cell viability, (v) colony-forming unit efficiency, and (vi) inflammatory
cytokine expression. Under normoxia (21% O2), cells from preterm and term infants
had similar properties. Under hypoxic conditions (1% O2), term MSCs had better
cell proliferation; however, cells exposed to hyperoxia (90% O2) had the slowest
motility and lowest cell viability (p < 0.05). There was no difference in the
expression of senescence or cytokine expression between the groups. The term
cells demonstrated more colony-forming efficiency than the preterm cells. In sum,
our preliminary findings suggest that MSCs derived from term and preterm
umbilical cords have similar characteristics, offering the potential of future
autologous/allogeneic MSC transplants in neonates.
PMID- 29949805
TI - 18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in
Human Pheochromocytomas.
AB - BACKGROUND: 18F-FDOPA positron emission tomography/computed tomography (PET/CT)
is a sensitive nuclear imaging technology for the diagnosis of pheochromocytomas
(PHEO). However, its utility in determining predictive factors for the secretion
of catecholamines remains poorly studied. METHODS: Thirty-nine histologically
confirmed PHEO were included in this retrospective single-center study. Patients
underwent 18F-FDOPA PET/CT before surgery, with an evaluation of several uptake
parameters (standardized uptake values [SUVmax and SUVmean] and the metabolic
burden [MB] calculated as follows: MB = SUVmean * tumor volume) and measurement
of plasma and/or urinary metanephrine (MN), normetanephrine (NM), and
chromogranin A. Thirty-five patients were screened for germline mutations in the
RET, SDHx, and VHL genes. Once resected, primary cultures of 5 PHEO were used for
real-time measurement of catecholamine release by carbon fiber amperometry.
RESULTS: The MB of the PHEO positively correlated with 24-h urinary excretion of
NM (r = 0.64, p < 0.0001), MN (r = 0.49, p = 0.002), combined MN and NM (r =
0.75, p < 0.0001), and eventually plasma free levels of NM (r = 0.55, p = 0.006).
In the mutated patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL, and 3 RET), a similar
correlation was observed between MB and 24-h urinary combined MN and NM (r =
0.86, p = 0.0012). For the first time, we demonstrate a positive correlation
between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule
fusion events of the corresponding PHEO cells revealed by amperometric spikes (p
= 0.01). CONCLUSION: While the 18F-FDOPA PET/CT MB of PHEO strongly correlates
with the concentration of MN, amperometric recordings suggest that 18F-FDOPA
uptake could be enhanced by overactivity of catecholamine exocytosis.
PMID- 29949806
TI - Accelerated Episodic Luteinizing Hormone Release Accompanies Blunted Progesterone
Regulation in PCOS-like Female Rhesus Monkeys (Macaca Mulatta) Exposed to
Testosterone during Early-to-Mid Gestation.
AB - BACKGROUND/AIMS: Ovarian theca cell hyperandrogenism in women with polycystic
ovary syndrome (PCOS) is compounded by androgen receptor-mediated impairment of
estradiol and progesterone negative feedback regulation of episodic luteinizing
hormone (LH) release. The resultant LH hypersecretion, likely the product of
accelerated episodic release of gonadotropin-releasing hormone (GnRH) from the
median eminence of the hypothalamus, hyperstimulates ovarian theca cell
steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally
androgenized (PA) female monkeys exposed to fetal male levels of T during early
to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and
LH levels. This study tests the hypothesis that progesterone resistance
associated acceleration in episodic LH release contributes to PA monkey LH
excess. METHODS: A total of 4 PA and 3 regularly cycling, healthy control adult
female rhesus monkeys of comparable age and body mass index underwent (1) a 10 h,
frequent intravenous sampling assessment for LH episodic release, immediately
followed by (2) IV infusion of exogenous GnRH to quantify continuing pituitary LH
responsiveness, and subsequently (3) an SC injection of a progesterone receptor
antagonist, mifepristone, to examine LH responses to blockade of progesterone
mediated action. RESULTS: Compared to controls, the relatively hyperandrogenic PA
females exhibited ~100% increase (p = 0.037) in LH pulse frequency, positive
correlation of LH pulse amplitude (p = 0.017) with androstenedione, ~100% greater
increase (p = 0.034) in acute (0-10 min) LH responses to exogenous GnRH, and an
absence (p = 0.008) of modest LH elevation following acute progesterone receptor
blockade suggestive of diminished progesterone negative feedback. CONCLUSION:
Such dysregulation of LH release in PCOS-like monkeys implicates impaired
feedback control of episodic release of hypothalamic GnRH reminiscent of PCOS
neuroendocrinopathy.
PMID- 29949807
TI - Quantitative Criteria to Screen for Cannabis Use Disorder.
AB - INTRODUCTION: The Standard Joint Unit (1 SJU = 7 mg of 9-Tetrahydrocannabinol)
simplifies the exploration of risky patterns of cannabis use. This study proposes
a preliminary quantitative cutoff criterion to screen for cannabis use disorder
(CUD). METHODOLOGY: Socio-demographical data and information on cannabis
quantities, frequency of use, and risk for CUD (measured with the Cannabis Abuse
Screening Test (CAST) of cannabis users recruited in Barcelona (from February
2015 to June 2016) were collected. CAST scores were categorized into low,
moderate, and high risk for CUD, based on the SJU consumed and frequency.
Receiver operating characteristic (ROC) analysis related daily SJU with CUD.
RESULTS: Participants (n = 473) were on average 29 years old (SD = 10), men
(77.1%), and single (74.6%). With an average of 4 joints per smoking day, 82.5%
consumed cannabis almost every day. Risk for CUD (9.40% low, 23.72% moderate,
66.88% high) increased significantly with more frequency and quantities consumed.
The ROC analyses suggest 1.2 SJU per day as a cutoff criterion to screen for at
least moderate risk for CUD (sensitivity 69.4%, specificity 63.6%). CONCLUSION:
Frequency and quantity should be considered when exploring cannabis risks. A 1
SJU per day is proposed as a preliminary quantitative-based criterion to screen
users with at least a moderate risk for CUD.
PMID- 29949808
TI - Simultaneous Study of Mechanical Stretch-Induced Cell Proliferation and Apoptosis
on C2C12 Myoblasts.
AB - Mechanical stretch may cause myoblasts to either proliferate or undergo
apoptosis. Identifying the molecular events that switch the fate of a stretched
cell from proliferation to apoptosis is practically important in the field of
regenerative medicine. A recent study on vascular smooth muscle cells illustrated
that identification of these events may be achieved by addressing the stretch
induced opposite cellular outcomes simultaneously within a single investigation.
To define conditions or a model in which both proliferation and apoptosis can be
studied at the same time, we exposed in vitro cultured C2C12 myoblasts to a
cyclic mechanical stretch regimen of 15% elongation at a stretching frequency of
1 Hz for 0, 2, 4, 6, or 8 h every day, consecutively, for 3 days. Both
proliferation and apoptosis were observed. Moreover, as the duration of the
stretch was prolonged, cell proliferation increased until it peaked at the
optimal stretching duration. Afterwards, apoptosis gradually prevailed.
Therefore, we established a model in which stretch-induced cell proliferation and
apoptosis can be studied simultaneously.
PMID- 29949809
TI - PKD Phosphorylation as Novel Pathway of KV11.1 Regulation.
AB - BACKGROUND/AIMS: The voltage-gated potassium channel KV11.1 has been originally
cloned from the brain and is expressed in a variety of tissues. The role of
phosphorylation for channel function is a matter of debate. In this study, we
aimed to elucidate the extent and role of protein kinase D mediated
phosphorylation. METHODS: We employed mass spectrometry, whole-cell patch clamp
electrophysiology, confocal microscopy, site-directed mutagenesis, and western
blotting. RESULTS: Using brain tissue from rat and mouse, we mapped several
phosphorylated KV11.1 residues by LC-MS mass spectrometry and identified protein
kinase D (PKD1) as possible regulatory kinase. Co-expression of KV11.1 with PKD1
reduced current amplitudes without altering protein levels or surface expression
of the channel. Based on LC-MS results from in vivo and HEK293 cell experiments
we chose four KV11.1 mutant candidates for further functional analysis. Ablation
of the putative PKD phosphorylation site in the mutant S284A increased the
maximal current indicating S284 as a main PKD target in KV11.1. CONCLUSIONS: Our
data might help mitigating a long-standing controversy in the field regarding PKC
regulation of KV11.1. We propose that PKD1 mediates the PKC effects on KV11.1 and
we found that PKD targets S284 in the N-terminus of the channel.
PMID- 29949810
TI - Can Ureteral Jet Flow Measurement Predict Spontaneous Passage of Distal Ureteral
Stones?
AB - OBJECTIVES: The study aimed to investigate the relationship between the
spontaneous passage of distal ureteral stones and ureteral jet flow measurement.
METHODS: The study included 74 patients with acute renal colic between June 2015
and June 2016, and distal ureteral stones of 10 mm or less in a non-contrast CT
were comprised in a prospective study. The ureteral jet was measured by Doppler
ultrasonography. At the fourth week follow-up, kidney-ureter-bladder radiography
was taken and the patients who no longer had a stone were considered to have
spontaneously passed it. RESULTS: The average stone size of the patients was 5.6
+/- 2.0 mm. After 4 weeks of follow-up, 55 patients (74.3%) had passed the stone
spontaneously whereas 19 (25.6%) had not. The patients in the former group were
found to have a higher peak flow velocity of ureteral jet on the stone side than
those in the latter group. In regression analysis ureteral jet on the stone side
was independently associated with spontaneous passage (p = 0.027). For the
spontaneous passage, a ureteral jet flow peak velocity above 15.25 cm/s had an
85.4% sensitivity and 63.1% specificity. CONCLUSIONS: Measurement of the ureteral
jet flow peak velocity can be beneficial in predicting the potential spontaneous
passage of distal ureteral stones.
PMID- 29949811
TI - Fournier's Gangrene: Literature Review and Clinical Cases.
AB - BACKGROUND: Fornier gangrene is an extremely rare disease of the genitals. This
disease is a result of the urogenital tract, anorectal area, and genital skin
infections, appearing usually in immunocompromised patients with diabetes,
obesity, and malignant neoplasms. The basic treatment of Fournier gangrene
includes an emergency surgical intervention combined with antibiotic therapy and
detoxification. METHODS: A review of recent papers comprising studies and reviews
published in 2005-2016 was performed. The clinical cases were studied at the
Department of Purulent Surgery Central Clinical Hospital No. 1, where 7 patients
were diagnosed and treated. RESULTS: The etiology, pathogenesis, clinical and
laboratory presentation, diagnosis, treatment, and prognosis of Fournier gangrene
are described in this article. The authors have described several clinical cases
of patients with Fournier gangrene and with necrotic cellulitis and
fasciomyositis of anterior abdominal wall, which is a manifestation of Fournier
gangrene. Making allowance for the unfavorable epidemiological situation of
syphilis in Russia, the increase in the incidence of complicated, atypical
chancre, and therefore, the need for differentiation of Fournier gangrene with
such manifestations of syphilis as necrotizing, esthiomenous chancre, indurative
edema, the appropriate clinical examples are well explained in this article.
PMID- 29949813
TI - Erratum: Use of Social Media and an Online Survey to Discuss Complex
Reconstructive Surgery: A Case of Upper Lip Reconstruction with 402 Responses
from International Microsurgeons.
PMID- 29949812
TI - Effects of Tumor Necrosis Factor alpha (TNF-alpha) and Interleukina 10 (IL-10) on
Intercellular Cell Adhesion Molecule-1 (ICAM-1) and Cluster of Differentiation 31
(CD31) in Human Coronary Artery Endothelial Cells.
AB - BACKGROUND The aim of this study was to investigate the effects of TNF-alpha and
IL-10 on the expression of ICAM-1 and CD31 in human coronary artery endothelial
cells (HCAEC). MATERIAL AND METHODS HCAEC was treated with 0, 2.5 MUg/l, 5 MUg/l,
and 10 MUg/l of TNF-alpha for 2 h, 6 h, and 10 h, and with 0 MUg/l, 10 MUg/l, 100
MUg/l, and 200 MUg/l of IL-10 for 5 h, 10 h and 15 h, respectively. RNA inference
of TNF-alphaR was performed with siRNA. Real-time PCR, Western blot analysis, and
ELSA were used to detect the mRNA level and protein level of ICAM-1 and CD31.
RESULTS TNF-alpha significantly increased the mRNA and protein expression of ICAM
1 (P<0.05), and 2.5 MUg/l TNF-alpha had the most obvious effect. RNAi of TNF-aR
reduced the induction of TNF-alpha on the mRNA and protein expression of ICAM-1
(P<0.05). TNF-alpha significantly decreased the CD31 in the supernatant (P<0.05),
and 2.5 MUg/l TNF-a had the most obvious effect. IL-10 significantly decreased
the ICAM-1 protein level. IL-10 decreased the mRNA expression and the protein
expression of CD31. The effect on mRNA was not significant (P>0.05), while the
effect on the protein expression was significant (P<0.05). CONCLUSIONS TNF-alpha
and IL-10 treatment can affect the expression of ICAM-1 and CD31 in HCAEC.
PMID- 29949814
TI - Resident and Fellow Section in Neuropediatrics.
PMID- 29949815
TI - Usability Assessment of Secure Messaging for Clinical Document Sharing between
Health Care Providers and Patients.
AB - BACKGROUND: Web-based patient portals feature secure messaging systems that
enable health care providers and patients to communicate information. However,
little is known about the usability of these systems for clinical document
sharing. OBJECTIVE: This article evaluates the usability of a secure messaging
system for providers and patients in terms of its ability to support sharing of
electronic clinical documents. METHODS: We conducted usability testing with
providers and patients in a human-computer interaction laboratory at a Midwestern
U.S. hospital. Providers sent a medication list document to a fictitious patient
via secure messaging. Separately, patients retrieved the clinical document from a
secure message and returned it to a fictitious provider. We collected use errors,
task completion, task time, and satisfaction. RESULTS: Twenty-nine individuals
participated: 19 providers (6 physicians, 6 registered nurses, and 7 pharmacists)
and 10 patients. Among providers, 11 (58%) attached and sent the clinical
document via secure messaging without requiring assistance, in a median (range)
of 4.5 (1.8-12.7) minutes. No patients completed tasks without moderator
assistance. Patients accessed the secure messaging system within 3.6 (1.2-15.0)
minutes; retrieved the clinical document within 0.8 (0.5-5.7) minutes; and sent
the attached clinical document in 6.3 (1.5-18.1) minutes. Although median
satisfaction ratings were high, with 5.8 for providers and 6.0 for patients
(scale, 0-7), we identified 36 different use errors. Physicians and pharmacists
requested additional features to support care coordination via health information
technology, while nurses requested features to support efficiency for their
tasks. CONCLUSION: This study examined the usability of clinical document
sharing, a key feature of many secure messaging systems. Our results highlight
similarities and differences between provider and patient end-user groups, which
can inform secure messaging design to improve learnability and efficiency. The
observations suggest recommendations for improving the technical aspects of
secure messaging for clinical document sharing.
PMID- 29949817
TI - Primary Amenorrhea Associated with Hyperprolactinemia in Polyglandular Autoimmune
Syndrome Type II: A Case Report.
AB - Polyglandular autoimmune syndrome type II (PGA-II) is a rare immunoendocrinopathy
syndrome characterized by the occurrence of autoimmune Addison disease along with
diabetes mellitus type 1 and/or autoimmune thyroid disease. Here, we report the
case of a 23-year-old female with PGA-II who was followed up at the dermatology
and endocrinology clinics of the Universidade Federal do Triangulo Mineiro,
located in the state of Minas Gerais, Brazil. First, the patient presented
diffuse skin hyperpigmentation, vitiligo; and in sequence, due to vomiting,
appetite and weight loss, hypoglycemia, amenorrhea, and galactorrhea, the patient
was then diagnosed with PGA-II. The patient also presented intense
hyperprolactinemia due to primary hypothyroidism. The late diagnosis of PGA-II is
frequent because the disorder is uncommon and has non-specific clinical
manifestations. This report emphasizes the significance of a timely diagnosis and
appropriate treatment to reduce morbidity and mortality associated with these
diseases, especially Addison disease. The present study reports a rare case of a
patient with PGA-II with primary amenorrhea associated with hyperprolactinemia.
PMID- 29949816
TI - Incorporating Guideline Adherence and Practice Implementation Issues into the
Design of Decision Support for Beta-Blocker Titration for Heart Failure.
AB - BACKGROUND: The recognition of and response to undertreatment of heart failure
(HF) patients can be complicated. A clinical reminder can facilitate use of
guideline-concordant beta-blocker titration for HF patients with depressed
ejection fraction. However, the design must consider the cognitive demands on the
providers and the context of the work. OBJECTIVE: This study's purpose is to
develop requirements for a clinical decision support tool (a clinical reminder)
by analyzing the cognitive demands of the task along with the factors in the
Cabana framework of physician adherence to guidelines, the health information
technology (HIT) sociotechnical framework, and the Promoting Action on Research
Implementation in Health Services (PARIHS) framework of health services
implementation. It utilizes a tool that extracts information from medical records
(including ejection fraction in free text reports) to identify qualifying
patients at risk of undertreatment. METHODS: We conducted interviews with 17
primary care providers, 5 PharmDs, and 5 Registered Nurses across three Veterans
Health Administration outpatient clinics. The interviews were based on cognitive
task analysis (CTA) methods and enhanced through the inclusion of the Cabana, HIT
sociotechnical, and PARIHS frameworks. The analysis of the interview data led to
the development of requirements and a prototype design for a clinical reminder.
We conducted a small pilot usability assessment of the clinical reminder using
realistic clinical scenarios. RESULTS: We identified organizational challenges
(such as time pressures and underuse of pharmacists), knowledge issues regarding
the guideline, and information needs regarding patient history and treatment
status. We based the design of the clinical reminder on how to best address these
challenges. The usability assessment indicated the tool could help the decision
and titration processes. CONCLUSION: Through the use of CTA methods enhanced
with adherence, sociotechnical, and implementation frameworks, we designed a
decision support tool that considers important challenges in the decision and
execution of beta-blocker titration for qualifying HF patients at risk of
undertreatment.
PMID- 29949819
TI - Video Comment on Kazuya Takahashi et al.
PMID- 29949818
TI - Surgical Treatment of Intestinal Endometriosis: Outcomes of Three Different
Techniques.
AB - OBJECTIVE: To outline the demographic and clinical characteristics of patients
with deep intestinal endometriosis submitted to surgical treatment at a tertiary
referral center with a multidisciplinary team, and correlate those
characteristics with the surgical procedures performed and operative
complications. METHODS: A prospective cohort from February 2012 to November 2016
of 32 women with deep intestinal endometriosis operations. The variables analyzed
were: age; obesity; preoperative symptoms (dysmenorrhea, dyspareunia, acyclic
pain, dyschezia, infertility, urinary symptoms, constipation and intestinal
bleeding); previous surgery for endometriosis; Enzian classification; size of the
intestinal lesion; and surgical complications. RESULTS: The mean age was 37.75
(+/-5.72) years. A total of 7 patients (22%) had a prior history of
endometriosis. The mean of the largest diameter of the intestinal lesions
identified intraoperatively was of 28.12 mm (+/-14.29 mm). In the Enzian
classification, there was a predominance of lesions of the rectum and sigmoid,
comprising 30 cases (94%). There were no statistically significant associations
between the predictor variables and the outcome complications, even after the
multiple logistic regression analysis. Regarding the size of the lesion, there
was also no significant correlation with the outcome complications (p = 0.18; 95%
confidence interval [95%CI]:0.94-1.44); however, there was a positive association
between grade 3 of the Enzia classification and the more extensive surgical
techniques: segmental intestinal resection and rectosigmoidectomy, with a
prevalence risk of 4.4 (p < 0.001; 95%CI:1.60-12.09). CONCLUSION: The studied
sample consisted of highly symptomatic women. A high prevalence of deep
infiltrative endometriosis lesions was found located in the rectum and sigmoid
region, and their size correlated directly with the extent of the surgical
resection performed.
PMID- 29949820
TI - Video Comment on Daisuke Maruoka et al.
PMID- 29949821
TI - Risk-stratified clinical management of superficially invasive esophageal squamous
cell carcinoma after endoscopic resection: finding the sweet spot.
PMID- 29949822
TI - If endoscopic mucosal resection is so great for large benign colon polyps, why is
so much surgery still being done?
PMID- 29949823
TI - Optimizing polypectomy practice: more cutting-edge research needed.
PMID- 29949824
TI - [French comment on article Management decision based on lymphovascular
involvement leads to favorable outcomes after endoscopic treatment of esophageal
squamous cell carcinoma].
PMID- 29949825
TI - [French comment on article Meta-analysis of randomized controlled trials
challenging the usefulness of purgative preparation before small-bowel video
capsule endoscopy].
PMID- 29949826
TI - [French comment on article The size, morphology, site, and access score predicts
critical outcomes of endoscopic mucosal resection in the colon].
PMID- 29949827
TI - [French comment on article Residual adenoma after cold snare polypectomy for
small colorectal adenomas: a prospective clinical study].
PMID- 29949828
TI - Is There Any Necessity to Prescribe Consumption of Walnuts Cooked by Different
Processing Techniques to Patients With Walnut Allergy?
AB - The present study focused on identifying the usual methods of cooking walnuts in
order to investigate changes in walnut allergen activity caused by cooking and
evaluated the allergenic changes in walnut proteins within raw, dry-fried and
boiled walnuts. Previous studies have reported a decrease in the allergen
activity of walnut by thermal processing methods, which are not used in Korean
kitchens, such as dry-frying and boiling. In Korea, Walnuts are consumed with
rice and usually boiled and stir-fried with seasoning. Thus, the present study
clarified the protein bands corresponding to raw walnuts and confirmed that the
patterns of each walnut protein differ depending on cooking methods. This concern
may be a very crucial point to understand the other tree nuts allergy as well as
walnut allergy. The results of the present study differ from those of previous
studies performed in Europe, although further studies with older participants are
needed in order to draw more definite conclusions on lipid transfer protein
(LTP). The other crucial point is that the findings of the present study support
existing findings that the allergenic components of walnut have varying
antigenicity depending on cooking methods. The allergenic components of walnut
identified using diagnostic tests for walnut allergic patients could be reduced
in walnuts cooked by different processing techniques. The allergenic components
of walnut have varying allergen activity depending on cooking methods. Therefore,
the allergenic components of walnuts identified using diagnostic tests for walnut
allergic patients could allow physicians to prescribe consumption of walnuts
cooked by different processing techniques to patients with walnut allergy.
PMID- 29949829
TI - How Different Parts of the World Provide New Insights Into Food Allergy.
AB - The prevalence and patterns of food allergy are highly variable in different
parts of the world. Differences in food allergy epidemiology may be attributed to
a complex interplay of genetic, epigenetic, and environmental factors, suggesting
that mechanisms of food allergy may differ in various global populations. Genetic
polymorphisms, migration, climate, and infant feeding practices all modulate food
allergy risk, and possibly also the efficacy of interventions aimed at primary
prevention of food allergy development. Approaches to diagnosis, treatment, and
prevention of food allergy should thus be tailored carefully to each population's
unique genetic and environmental make-up. Future research in the context of food
allergy prevention should focus on elucidating factors determining differential
responses between populations.
PMID- 29949831
TI - Microbiome in the Gut-Skin Axis in Atopic Dermatitis.
AB - The microbiome is vital for immune system development and homeostasis. Changes in
microbial composition and function, termed dysbiosis, in the skin and the gut
have recently been linked to alterations in immune responses and to the
development of skin diseases, such as atopic dermatitis (AD). In this review, we
summarize the recent findings on the gut and skin microbiome, highlighting the
roles of major commensals in modulating skin and systemic immunity in AD.
Although our understanding of the gut-skin axis is only beginning, emerging
evidence indicates that the gut and skin microbiome could be manipulated to treat
AD.
PMID- 29949832
TI - Immunoglobulin E-binding Proteins of Cooked Walnuts in Korean Children.
AB - PURPOSE: The immunological characteristics of young Korean children with walnut
(WN) allergy and the influence of different cooking methods on WN proteins have
not been evaluated to date. This study aimed to evaluate the major WN allergens
identified among Korean children, together with changes in WN antigenicity caused
by common cooking methods. METHODS: We enrolled children under the age of 13
years with WN serum-specific immunoglobulin (Ig) E concentrations. The protein
fractions of dry-fried and boiled WN extracts were compared with those of raw WNs
using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), 2
dimentional gel electrophoresis (2DE) and a proteomic analysis using electrospray
ionization (liquid chromatography-mass spectrometry [LC-MS]). An immunoblotting
analysis was conducted to examine IgE reactivity toward raw WNs using serum
samples from 6 children with a clinical WN allergy. To determine the processed WN
proteins with IgE-binding capacity, a 2D-immunoblotting analysis was performed
using the pooled sera of 20 WN-sensitized children. RESULTS: Protein bands from
raw WNs were identified at 9, 16, 28, 52, 58, and 64 kDa via SDS-PAGE. The 9- and
16-kDa protein bands were enhanced by boiling, whereas the 52- and 64-kDa bands
were considerably diminished. On LC-MS analysis, of the 66 IgE-binding proteins
present in raw WNs, 57 were found in dry-fried WNs, but only 4 in boiled WNs. The
sera of 5 out of 6 participants reacted with the 52-kDa protein bands and those
of 4 out of 6 participants reacted with the 16- and 28-kDa protein bands,
respectively. Meanwhile, a 2D-immunoblotting result confirmed the presence of
different binding patterns among children who consumed cooked WNs. CONCLUSIONS:
The protein profile of boiled WNs is substantially different from that of raw
WNs. However, 4 proteins including prolamins remained stable after dry-frying or
boiling. Further studies are needed to evaluate the clinical relevance of these
findings.
PMID- 29949833
TI - Economic Burden of the Inadequate Management of Allergic Rhinitis and Urticaria
in Asian Countries Based on the GA2LEN Model.
AB - PURPOSE: Across Hong Kong, Malaysia, the Philippines, Singapore, Thailand and
Vietnam, (referred to as Asia) approximately 30-53 million individuals of the 151
million employed suffer from allergic rhinitis (AR) and urticaria. It is
estimated that approximately 90% of patients with these allergic conditions are
insufficiently treated, impacting the socioeconomic burden in terms of absence
from work and decreased productivity. This study aims to estimate the
socioeconomic burden of allergies in Asia and the cost savings that their
adequate management can provide. Due to the limited availability of regional
data, this study focused AR and urticaria in selected countries. METHODS:
Published literature, information from statistical bureaus, clinician surveys and
extrapolation of selected data from the European Union were used to determine the
socioeconomic costs of AR and urticaria. RESULTS: Many patients in Asia suffer
from perennial allergies and experience symptoms of AR and urticaria for up to
298 days per year. An estimate of the indirect costs of patients insufficiently
treated for AR and urticaria amounts to USD 105.4 billion a year, which equates
to USD 1,137-2,195 per patient due to absenteeism and presenteeism. Adherence to
guideline-approved treatment can lead to estimated savings of up to USD 104
billion. CONCLUSIONS: The current study suggests that within Asia, the
socioeconomic impact of AR and urticaria is similar to that seen in the European
Union in spite of the lower wages in Asia. This is due to the mainly perennial
allergens prevailing in Asia, whereas the sensitization patterns observed in the
European Union are dominated by seasonal exposure to pollen. These results
underline the need for governmental initiatives to increase public awareness on
the prevention and treatment of these and other allergic diseases as well as
greater research funding and large-scale studies to reduce their growing
socioeconomic burden in coming years.
PMID- 29949834
TI - Factors Affecting Food Allergy-Related Quality of Life From Parents' Perception
in Turkish Children.
AB - PURPOSE: Food allergy (FA) affects the daily lives of children and parents in
varying degrees. The Food Allergy Quality of Life Questionnaire-Parent Form
(FAQLQ-PF) is a valid and reliable instrument to assess the quality of life (QoL)
of children from parents' perception. The aim of this study was to validate and
determine the reliability of the Turkish FAQLQ-PF and to assess QoL in food
allergic children. METHODS: Children aged between 0 and 12 years and diagnosed
with immunoglobulin E (IgE)-mediated FA for at least 1 month were enrolled. The
English FAQLQ-PF was translated into Turkish according to the World Health
Organization guidelines. The Food Allergy Independent Measure and the Turkish
Child Health Questionnaire-Parent Form 50 were used for construct validity.
RESULTS: One hundred and fifty-seven patients participated. The median age of
patients and FA duration were 2.4 years (1.2-5.2 years, interquartile-ranges) and
2 years (0.8-5.1), respectively. Ninety-six (61.1%) patients had anaphylaxis. The
Cronbach's alpha coefficient and intra-class correlation coefficient for test
retest reliability was good for all age groups of children (<4, 4-6, and 7-12
years). Patients with either asthma or anaphylaxis had worse scores than others.
Total scores of FAQLQ-PF tended to increase with age. Patients aged 7-12 had the
highest total scores among all patients (2.2+/-0.1, 3.0+/-0.2, and 3.3+/-0.3 for
<4, 4-6, and 7-12 years, respectively, P<0.001, P for trend <0.001). Other
factors causing the poor QoL were cow's milk allergy, sibling allergy, mother's
age over 30 years, mother's high education level and lower number of persons in
household. CONCLUSIONS: The Turkish FAQLQ-PF is a valid and reliable scale. FA
related QoL was significantly worse with age. Coexistent asthma, anaphylaxis
regardless of its severity, cow's milk allergy, sibling allergy and the older and
educated mothers seem to poorly affect QoL.
PMID- 29949835
TI - High Prevalence of Asthma in Elderly Women: Findings From a Korean National
Health Database and Adult Asthma Cohort.
AB - PURPOSE: The prevalence and burden of asthma is increasing worldwide. In this
study, we analyzed 3 different Korean national health survey datasets to
determine the general features of adult asthma in Korea and to obtain basic
information that would support future strategies for better management of adult
asthma. METHODS: The surveys used in this study included the Korea National
Health and Nutrition Examination Survey (KNHANES), Korea Community Health Survey
(KCHS) and National Health Insurance Service-National Sample Cohort (NHIS-NSC).
We investigated annual asthma prevalence, evaluating the rate and risk factors of
asthma exacerbation by age and sex, and clinical data of 1,832 patients with
asthma who were registered in the Cohort for Reality and Evolution of Adult
Asthma in Korea (COREA) were analyzed to elucidate risk factors for asthma
exacerbation. We also analyzed another asthma cohort and added it as replication
data. RESULTS: In the KNHANES database, annual asthma prevalence rates varied
from 1.2% to 3.1%. In the KCHS database, overall prevalence increased, with
significant regional differences (1.6%-2.1%). The NHIS-NSC indicated a gradual
increase in annual asthma prevalence from 4.5% to 6.2%. Interestingly, all 3
surveys indicated the highest prevalence of asthma among elderly women. In
addition, elderly women with asthma had a significantly higher risk of asthma
exacerbation (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.19-2.93;
P=0.006). Approximately 11% of patients were classified as having severe asthma.
An asthma cohort analysis identified female sex, low baseline pulmonary function,
longer treatment duration, high variability in pulmonary function and significant
changes in Asthma Control Test scores as risk factors for asthma exacerbation.
CONCLUSIONS: The prevalence of asthma in Korea is consistently high among elderly
and female populations. These results should lay the foundation for strategies
for effective asthma prevention and management; elderly female patients with
asthma should receive particular attention.
PMID- 29949836
TI - Association of Genetic Polymorphisms with Atopic Dermatitis, Clinical Severity
and Total IgE: A Replication and Extended Study.
AB - PURPOSE: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease
affecting up to 20% of children and 3% of adults worldwide. Although previous
reports including genome-wide association study (GWAS) approaches have identified
several risk factors that appear to be associated with AD development,
replication studies are lacking. In our current study, we replicated the
associations between candidate susceptibility loci and AD. METHODS: A total of
885 Korean subjects (425 AD patients and 460 unaffected controls) were genotyped
for 17 single nucleotide polymorphisms (SNPs) from previous GWASs and meta
analyses of AD and from immune-related genes. RESULTS: Several SNPs showed
significant associations with AD in the case-control analysis (minimum P=0.005 at
rs17389644), suggesting that these polymorphisms may be related to this disease.
In addition, several SNPs showed significant signals (minimum P=0.004 at
rs6473227) in severe AD compared to unaffected controls. In additional linear
regression analysis, a few genotypes appeared to have potential effects on the
SCORing AD (SCORAD) values (minimum P=0.003 at rs13361382 on TMEM232) and
immunoglobulin E (IgE) levels (minimum P<0.0001 at rs4713555 near HLA-DRB1 and
HLA-DQA1) in AD patients. CONCLUSIONS: Our replication and extended study provide
additional supporting information on the genetic associations (especially,
variants in TMEM232 and nearby to IL21 and HLA-DRB1/HLA-DQA1) related to AD, its
clinical severity and IgE involvement.
PMID- 29949837
TI - Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite
Triggered Allergic Inflammation.
AB - PURPOSE: The use of tolerogenic dendritic cells (TolDCs) to control exacerbated
immune responses may be a prophylactic and therapeutic option for application in
autoimmune and allergic conditions. The objective of this work was to evaluate
the effects of TolDC administration in a mouse model of allergic airway
inflammation caused by mite extract. METHODS: Mouse bone marrow-derived TolDCs
were induced by incubation with granulocyte-macrophage colony-stimulating factor
(GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine
production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of
Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs
were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed
to aluminium hydroxide. After challenge by nasal administration of BtE,
bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for
analysis. RESULTS: Induction of TolDCs was efficiently achieved as shown by low
expression of major histocompatibility complex (MHC) II, programmed death-ligand
(PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of
interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2
doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and
lungs as well as mucus deposition. Moreover, compared to saline-injected
controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin
E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs
and decreased IFN-gamma levels in the supernatant of splenocyte cultures
Transplantation of TolDCs increased the percentage of the regulatory T cells in
the spleen and the lungs. CONCLUSIONS: Preventive treatment with TolDCs protects
against dust mite-induced allergy in a mouse model, reinforcing the use of
tolerogenic dendritic cells for the management of allergic conditions.
PMID- 29949838
TI - The Incidence of Delayed-Type Hypersensitivity Reactions to Apples Among Patients
Allergic to Birch Pollen.
AB - The major apple allergen Mal d 1 cross-reacts with the homologous birch pollen
allergen Bet v 1 and causes immunoglobulin E (IgE)-mediated immediate-type
allergic reactions. In some patients, delayed-type hypersensitivity to apples may
develop within 72 hours without evidence of specific IgE or a positive skin prick
test (SPT). The aim of the study was to evaluate the concomitance of delayed-type
hypersensitivity reactions and immediate IgE-mediated reactions against high- and
low-allergenic apple cultivars in patients with birch pollen allergy. Data were
obtained from 45 adults with clinical symptoms of birch pollen allergy. Patients
were exposed to apple pulp via atopy patch tests (APTs) and SPTs. Levels of IgE
specific to Bet v 1 and Mal d 1 were measured with a radioallergosorbent test.
Patients allergic to birch pollen showed the highest rate of positive SPT
responses to Golden Delicious apples and the lowest rate to low-allergenic
cultivar Grey French Reinette. Among these patients, 9% developed delayed
hypersensitivity reactions to either Golden Delicious or Grey French Reinette
apples; these reactions manifested clinically as erythema with papules (class
++). Fifty percent of APT-positive patients were concomitantly SPT-negative.
Here, we show for the first time the clinical relevance of T cell-driven allergic
reactions to apples. APTs may reveal type IV sensitization in patients who are
negative for the corresponding type I sensitization tests. Thus, utilization of
the APT procedure with fresh apple appears to be a valuable tool for the
diagnosis of apple allergy and may improve the accuracy of food allergy
diagnoses.
PMID- 29949839
TI - Medicinals with properties of warming Yang and tonifying Qi in terms of
Traditional Chinese Medicine: their effects on left ventricularejection fraction
and aldosterone in rats with induced failure heart.
AB - OBJECTIVE: To investigate on Left ventricular ejection fraction value and
aldosterone of two medicinalsof Traditional Chinese Medicine (TCM) with the
properties of warming Yang and tonifying Qi interms of TCM theory. METHODS: An
animal model of coronary ligation of heart failure after myocardial infarction
was employedto study the influence of these two kinds of drugs on three batches
of rats. On the basis of theaverage score of left ventricle ejection fraction
during the investigation, there were some differentgroups, including WenYang (the
warming Yang) group, YiQi (tonifying Qi) group, WenYang and YiQigroup, captopril
group, digoxin group. In additional, an artificial operation group was set for
comparison The systemic intervention using these medicinal and drugs was taken
effects on the 2nd day afterthe operation of myocardial infraction (MI) with once
a day. At week one, two, and four after the MItreatment, evaluated were EF
values, and ferritin, angiotensin-II and aldosterone in the rats' plasma.
RESULTS: At week one and week two, the medicinal of WenYang, YiQi, WenYang pluse
YiQi, and digoxincould improve left ventricular ejection fraction in rats with
heart failure; Compared to themodel group, captopril Left ventricular EF value
increased, but there was not significant. At week four,heart failure and left
ventricular EF values was improved in the intervention group and the otherfour
captopril drug intervention. At week one in the rats with drug intervention, the
medicinals ofYiQi, WenYang plus YiQi, and captopril could inhibit activation in
vivo hormone aldosterone in heart failurerats; aldosterone in WenYang group and
digoxin group were not different from that in the model group at week two and
four. CONCLUSION: Chinese medicinals with properties of WenYang, YiQi have
significant effect on improvingleft ventricular EF in rats with heart failure;
compared to YiQi medicinals, WenYang medicinals thatinhibit the effectiveness of
the time required for the activation of the role of aldosterone. The medicinalsof
WenYang and YiQi seems better by inhibiting the activation of the hormone
aldosterone afterfailing to inhibit ventricular remodeling to improve heart
failure.
PMID- 29949840
TI - Antifungal, phytotoxic and hemagglutination activity of methanolic extracts of
Ocimum basilicum.
AB - OBJECTIVE: To report some of the pharmacological features of the medicinal plant
Ocimum basilicum. METHODS: In the current studies, Antifungal activity of crude
methanolic fraction of Ocimum basilicumwas determined against eight pathogenic
fungal strains using tube dilution assay. The methanolicfraction was also
investigated for phytotoxic and hemagglutination activity. RESULTS: Of the eight
strains investigated only Candida albicans and Curvilaria lunata were foundto be
least affected by plant extract while the rest were significantly inhibited.
Moderate phytotoxicactivity was observed against lemna minor. Hemagglutination
activity showed absence of phytolectinsand hence no agglutination of
erythrocytes. CONCLUSION: The crude extract of Ocimum basilicum has significant
properties against fungi and phytotoxic substances.
PMID- 29949841
TI - Anti-infectious efficacy of essential oil from Caoguo (Fructus Tsaoko).
AB - OBJECTIVE: To evaluate the anti-infectious efficacy of essential oil extracted
from Caoguo (Fructus Tsaoko). METHODS: Minimum inhibitory concentrations (MICs)
against clinical isolates of three extracts and the essential oil from Caoguo
(Fructus Tsaoko) were determined by the agar dilution method. The antiinfectious
efficacy of the essential oil was evaluated using a mouse peritonitis model which
was infected with Staphylococcus aureus or Escherichia coli. The chemical
components of the essential oil were identified. RESULTS: The results showed that
the essential oil exhibited strong antibacterial activity in vitro, withMICs
ranging from 22.49 to 1438.91 MUg/mL. The results of in vivo anti-infectious
efficacy showed thatthe Caoguo (Fructus Tsaoko) essential oil can protect the
mice from Staphylococcus aureus or Escherichiacoli infection. The compositions of
the essential oil and relative component percentages wereexamined. A total of 32
compounds, were identified. The major compounds of essential oil were 1, 8
cineole (25.92%) and geraniol (13.69%). CONCLUSION: Our findings suggest that
Caogu (Fructus Tsaoko) essential oil has broad-spectrum antibacterial properties.
It warrants further investigation as an antibacterial agent targeting some
bacterium with multi-drug resistance.
PMID- 29949830
TI - Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic
Rhinitis.
AB - Allergic rhinitis (AR) is a global health problem that causes major illnesses and
disabilities worldwide. Epidemiologic studies have demonstrated that the
prevalence of AR has increased progressively over the last few decades in more
developed countries and currently affects up to 40% of the population worldwide.
Likewise, a rising trend of AR has also been observed over the last 2-3 decades
in developing countries including China, with the prevalence of AR varying widely
in these countries. A survey of self-reported AR over a 6-year period in the
general Chinese adult population reported that the standardized prevalence of
adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of
Journal Articles and imporclinical trials on the epidemiology, pathophysiologic
mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects
have been published in international peer-reviewed journals over the past 2
decades, and substantially added to our understanding of this disease as a global
problem. Although guidelines for the diagnosis and treatment of AR in Chinese
subjects have also been published, they have not been translated into English and
therefore not generally accessible for reference to non-Chinese speaking
international medical communities. Moreover, methods for the diagnosis and
treatment of AR in China have not been standardized entirely and some patients
are still treated according to regional preferences. Thus, the present guidelines
have been developed by the Chinese Society of Allergy to be accessible to both
national and international medical communities involved in the management of AR
patients. These guidelines have been prepared in line with existing international
guidelines to provide evidence-based recommendations for the diagnosis and
management of AR in China.
PMID- 29949842
TI - Effect of moxa smoke produced during combustion of Aiye (Folium Artemisiae Argyi)
on behavioral changes in mice inhaling the smoke.
AB - OBJECTIVE: To evaluate the effects that inhalation of the combustion products of
the traditional Chinese herb Aiye (Folium Artemisiae Argyi) has on the central
nervous system. METHODS: Forty Kunming mice (half male) were randomly assigned (n
= 10/group) to a controlgroup (C) or one of three moxa smoke concentration groups
(% opacity): low (L1; 0.4% ), medium(M1; 2% ), and high (H1; 15% ). Mice in the
latter three groups were exposed to moxa smoke in a dynamicgas exposure cabinet
for 20 min per day for 7 days. Mice in control group were placed in thesame
cabinet without any intervention. For the sleep experiments, another 50 mice were
dividedinto five groups of 10 mice each: a saline-injected control group, L1 +
pentobarbital sodium (PS)-injectedgroup, M1 + PS group, H1 (15% ) + PS group, and
a positive control group (10 mg/kg, chlorpromazine,p.o.). The weight, general
activities, locomotor activities, rotarod performance, sleep duration,and
sleeping rate induced by a subthreshold dose of pentobarbital sodium were
recorded in the mice,and the composition of moxa smoke was analyzed using
headspace gas chromatography (GC-HS). RESULTS: A low concentration of smoke
significantly decreased the frequency of locomotor activitiesand the time for
which the mice remaining on the rotarod; however, a high smoke concentration
significantlyprolonged the pentobarbital-induced sleeping time and sleeping rate.
CONCLUSION: The concentration-dependent relaxing effects of moxa smoke on the
Central NervousSystem (CNS) were confirmed. Moreover, GC-HS analysis showed that
the component present in thehighest concentration in moxa smoke was eucalyptol,
an essential oil well recognized for its soothingeffects on the CNS. This may
therefore be accountable for the sedative effects of moxa smoke.
PMID- 29949843
TI - Sex Differences in Cancer: Epidemiology, Genetics and Therapy.
AB - The incidence and mortality of various cancers are associated with sex-specific
disparities. Sex differences in cancer epidemiology are one of the most
significant findings. Men are more prone to die from cancer, particularly
hematological malignancies. Sex difference in cancer incidence is attributed to
regulation at the genetic/molecular level and sex hormones such as estrogen. At
the genetic/molecular level, gene polymorphism and altered enzymes involving drug
metabolism generate differences in cancer incidence between men and women. Sex
hormones modulate gene expression in various cancers. Genetic or hormonal
differences between men and women determine the effect of chemotherapy. Until
today, animal studies and clinical trials investigating chemotherapy showed sex
imbalance. Chemotherapy has been used without consideration of sex differences,
resulting in disparity of efficacy and toxicity between sexes. Based on
accumulating evidence supporting sex differences in chemotherapy, all clinical
trials in cancer must incorporate sex differences for a better understanding of
biological differences between men and women. In the present review, we
summarized the sex differences in (1) incidence and mortality of cancer, (2)
genetic and molecular basis of cancer, (3) sex hormones in cancer incidence, and
(4) efficacy and toxicity of chemotherapy. This review provides useful
information for sex-based chemotherapy and development of personalized
therapeutic strategies against cancer.
PMID- 29949844
TI - Does exposure to reduced pH and diclofenac induce oxidative stress in marine
bivalves? A comparative study with the mussel Mytilus galloprovincialis and the
clam Ruditapes philippinarum.
AB - CO2-driven acidification and emerging contaminants, such as pharmaceuticals, pose
new threats for the maintenance of natural populations of marine organisms by
interfering with their normal biochemical pathways and defences. The combined
effects of seawater acidification, as predicted in climate change scenarios, and
an emerging contaminant (the non-steroidal anti-inflammatory drug, NSAID,
diclofenac) on oxidative stress-related parameters were investigated in the
Mediterranean mussel Mytilus galloprovincialis and the Manila clam Ruditapes
philippinarum. A flow-through system was used to carry out a three-week exposure
experiment with the bivalves. First, the animals were exposed to only three pH
values for 7 days. The pH was manipulated by dissolving CO2 in the seawater to
obtain two reduced pH treatments (pH -0.4 units and pH -0.7 units), which were
compared with seawater at the natural pH level (8.1). Thereafter, the bivalves
were concomitantly exposed to the three experimental pH values and
environmentally relevant concentrations of diclofenac (0.00, 0.05 and 0.50 MUg/L)
for an additional 14 days. The activities of superoxide dismutase, catalase and
cyclooxygenase, and lipid peroxidation and DNA strand-break formation were
measured in both the gills and digestive gland after 7, 14 and 21 days of
exposure to each experimental condition. The results show that the biochemical
parameters measured in both the mussels and clams were more influenced by the
reduced pH than by the contaminant or the pH*contaminant interaction, although
the biomarker variation patterns differed depending on the species and tissues
analysed. Generally, due to increases in its antioxidant defence, M.
galloprovincialis was more resistant than R. philippinarum to both diclofenac
exposure and reduced pH. Conversely, reduced pH induced a significant decrease in
COX activity in both the gills and digestive gland of clams, possibly resulting
in the increased DNA damage observed in the digestive gland tissue.
PMID- 29949845
TI - Deep urban groundwater vulnerability in India revealed through the use of
emerging organic contaminants and residence time tracers.
AB - Demand for groundwater in urban centres across Asia continues to rise with ever
deeper wells being drilled to avoid shallow contamination. The vulnerability of
deep alluvial aquifers to contaminant migration is assessed in the ancient city
of Varanasi, India, using a novel combination of emerging organic contaminants
(EOCs) and groundwater residence time tracers (CFC and SF6). Both shallow and
intermediate depth private sources (<100 m) and deep (>100 m) municipal
groundwater supplies were found to be contaminated with a range of EOCs including
pharmaceuticals (e.g. sulfamethoxazole, 77% detection frequency, range <0.0001
0.034 MUg L-1), perfluoroalkyl substances (e.g. PFOS, range <0.0001-0.033 MUg L
1) as well as a number of pesticides (e.g. phenoxyacetic acid, range <0.02-0.21
MUg L-1). The profile of EOCs found in groundwater mirror those found in surface
waters, albeit at lower concentrations, and reflect common waste water sources
with attenuation in the subsurface. Mean groundwater residence times were found
to be comparable between some deep groundwater and shallow groundwater sources
with residence times ranging from >70 to 30 years. Local variations in aquifer
geology influence the extent of modern recharge at depth. Both tracers provide
compelling evidence of significant inputs of younger groundwater to depth >100 m
within the aquifer system.
PMID- 29949846
TI - Nitric oxide confronts arsenic stimulated oxidative stress and root architecture
through distinct gene expression of auxin transporters, nutrient related genes
and modulates biochemical responses in Oryza sativa L.
AB - Plants have the ability to adapt themselves under stressed conditions through
reprogramming their growth and development. Understanding the mechanisms
regulating overall growth of stressed plant is an important issue for plant and
environmental biology research. Although the role of NO in modulating arsenic
(As) toxicity is known, nitric oxide (NO) induced alteration in auxin and
nutrient related transporters during As stress in rice is poorly understood.
Experimental results showed that As exposure decreased gene expression level of
polar auxin transporter (PIN proteins), and nutrient transporter related genes
(AMT, NRT, NiR, PHT, KTP). The improved tolerance induced by As + NO combination
is attributed to reduced As accumulation in rice seedlings, improved root
architectural changes, overall growth of plant, chlorophyll, protein content, and
accumulation of mineral nutrients by reducing the ROS generation. Further,
enhanced transcript levels of PIN proteins and mineral nutrition related genes
were also observed under As + NO treatment. Additional biochemical data revealed
enhanced oxidative stress by increasing the level of antioxidant enzymes, and
stress-related parameters. Overall, the study provides an integrated view of
plant response during As + NO interaction to change the plant metabolism through
different cellular processes.
PMID- 29949847
TI - Cholinesterase Inhibition Activity, Alkaloid Profiling and Molecular Docking of
Chilean Rhodophiala (Amaryllidaceae).
AB - Amaryllidaceae plants are the commercial source of galanthamine, an alkaloid
approved for the clinical treatment of Alzheimer’s disease. The chemistry
and bioactivity of Chilean representatives of Rhodophiala genus from the family
of Amaryllidaceae have not been widely studied so far. Ten collections of five
different Chilean Rhodophiala were analyzed in vitro for activity against enzymes
such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) as well as
for their alkaloid composition by GC-MS. To obtain an insight into the potential
AChE and BuChE inhibitory activity of the alkaloids identified in the most active
samples, docking experiments were carried out. Although galanthamine was found
neither in aerial parts nor in bulbs of R. splendens, these plant materials were
the most active inhibitors of AChE (IC50: 5.78 and 3.62 μg/mL, respectively)
and BuChE (IC50: 16.26 and 14.37 μg/mL, respectively). Some 37 known alkaloids
and 40 still unidentified compounds were detected in the samples, suggesting high
potential in the Chilean Amaryllidaceae plants as sources of both novel bioactive
agents and new alkaloids.
PMID- 29949848
TI - Time Spent in Sedentary Behaviour as Discriminant Criterion for Frailty in Older
Adults.
AB - This paper aims to analyse whether time spent in sedentary behaviour was a
discriminant criterion for frailty in older adults. This was a cross-sectional
study conducted in a sample of 457 elderly individuals aged ≥60 years. Frailty
was defined as the presence of three or more of the following criteria:
Unintentional weight loss, low walking speed at a 4.57 m course, reduced manual
grip strength, exhaustion and insufficient physical activity level. Participants
were classified into two groups: Non-frail or frail. Exposure to sedentary
behaviour was assessed by the time spent sitting during a typical week, according
to the adapted version of the International Physical Activity Questionnaire.
Descriptive (mean, frequency) and inferential statistics (Poisson regression,
Pearson’s Chi-square, Receiver Operating Characteristic Curve) were used to
analyse the data, comparing them to the time-related areas exposed to sedentary
behaviour by gender and the presence of fragility. The prevalence of frailty was
22.1% (n = 101). The most accurate cut-off points of sitting time for predicting
frailty were >495 min/day (men) or >536 min/day (women). Time spent in sedentary
behaviour can be used to indicate fragility in the elderly of both sexes.
PMID- 29949849
TI - Temporal Trends in Sports Participation among Adolescents between 2001 and 2015:
A French School- and Territory-Based Study.
AB - Improving adolescents’ levels of sport and physical activity (PA) is an
official public health issue. French national government plans were launched in
2001, 2006, and 2011 to improve the participation levels of citizens. These plans
should be monitored. To date, information on temporal trends in sports has come
from the national population. However, no data are available to measure temporal
trends in different territories across the country. Our study aimed to measure
these trends among a representative sample of adolescent students of the third
biggest French region (Bouches-du-Rhône), but also one of the poorest,
between 2001 and 2015. Three surveys were conducted in 2001, 2008, and 2015 in
high schools (n = 3218). Logistic regressions adjusted for age were used to
determine the impact of socioeconomic status (SES) on sports participation and to
measure the changes in sport participation rates. Participation declined among
all subgroups of adolescents: from 79.0% to 65.8%. The greatest decrease was
observed for boys with a high SES, whilst the lowest was for the high-SES girls.
We observed that SES inequalities in access to sport increased among the girls,
whilst they reduced among the boys. National government plans seem to have had
limited success in this territory. Next to national studies, there is a need to
develop territory specific studies which could show important disparities across
the national territory.
PMID- 29949850
TI - Indoor Radon Gas (222Rn) Levels in Homes in Aldama, Chihuahua, Mexico and the
Risk of Lung Cancer.
AB - Radon (222Rn) is an odorless and tasteless gas that is known to cause lung
cancer. The objective of this research was to quantify the levels of exposure to
radon among people living in an environment rich in uranium (U). Radon
concentrations were measured for 3 days in 12 homes in Aldama, Mexico. Homeowners
agreed to participate in the study; hence, the sample was non-probabilistic.
Radon was measured with a portable AlphaGuard Radon Monitor (Genicron Instruments
GmbH), which was placed in a bedroom of each home at a height of 0.74 m. Gas
levels were registered in Becquerels (Bq m−3), with readings taken every 10
min along with readings of ambient temperature (AT), air pressure (AP), and
relative humidity (RH). We found that radon gas levels in Aldama exceed the
maximum permissible limits (USA: 148 Bq m−3). Levels were higher at night,
and were above the maximum permissible level recommended by the International
Atomic Energy Agency of the United Nations (<200 Bq m−3). Most residents in
the area have family histories of lung problems, but it was difficult to
establish a strong correlation between 222Rn and lung cancer. Federal, state, and
municipal governments should take stronger action to reduce the effects of radon
gas on communities.
PMID- 29949851
TI - Neopterin, Inflammation, and Oxidative Stress: What Could We Be Missing?
AB - Neopterin has been extensively used as a clinical marker of immune activation
during inflammation in a wide range of conditions and stresses. However, the
analysis of neopterin alone neglects the cellular reactions that generate it in
response to interferon-γ. Neopterin is the oxidation product of 7,8
dihydroneopterin, which is a potent antioxidant generated by interferon-γ
activated macrophages. 7,8-Dihydroneopterin can protect macrophage cells from a
range of oxidants through a scavenging reaction that generates either neopterin
or dihydroxanthopterin, depending on the oxidant. Therefore, plasma and urinary
neopterin levels are dependent on both macrophage activation to generate 7,8
dihydroneopterin and subsequent oxidation to neopterin. This relationship is
clearly shown in studies of exercise and impact-induced injury during intense
contact sport. Here, we argue that neopterin and total neopterin, which is the
combined value of 7,8-dihydroneopterin and neopterin, could provide a more
comprehensive analysis of clinical inflammation than neopterin alone.
PMID- 29949852
TI - Properties and Stability of Perilla Seed Protein-Stabilized Oil-in-Water
Emulsions: Influence of Protein Concentration, pH, NaCl Concentration and Thermal
Treatment.
AB - Perilla seed protein (PSP) was extracted from defatted perilla seed meal and
applied in oil-in-water (O/W) emulsions as an emulsifier. We investigated the
influences of protein concentration (0.25-1.5 wt %), pH (3.0-9.0), NaCl
concentration (0-350 mmol/L) and thermal treatment (70-90 °C, 30 min) on the
physical characteristics of O/W emulsions, including volume-average diameter,
ζ-potential, interfacial protein concentration, microstructure and so on.
Results showed that increasing PSP concentration would decrease the d4,3 and a
1.0 wt % PSP concentration was sufficient to ensure the stability of emulsion.
Under pH 3.0-9.0, emulsions were stable except at pH 3.0-5.0 which was proximal
to the isoelectric point (pH 4.5) of PSP. At high NaCl concentrations (250-350
mmol/L), the emulsions exhibited relatively lower absolute ζ-potential
values and a large number of aggregated droplets. A moderate thermal treatment
temperature (e.g., 70 °C) was favorable for the emulsion against aggregation
and creaming. However, when 90 °C thermal treatment was performed, a clear
layer separation was observed after 2 weeks storage and the emulsion showed a
poor stability. The findings of this work are of great importance for the
utilization and development of PSP as an emulsifier for food emulsions.
PMID- 29949853
TI - Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the
Cyanobacterium Nostoc edaphicum CCNP1411.
AB - Cyanopeptolins (CPs) are one of the most frequently occurring cyanobacterial
peptides, many of which are inhibitors of serine proteases. Some CP variants are
also acutely toxic to aquatic organisms, especially small crustaceans. In this
study, thirteen CPs, including twelve new variants, were detected in the
cyanobacterium Nostoc edaphicum CCNP1411 isolated from the Gulf of Gdansk
(southern Baltic Sea). Structural elucidation was performed by tandem mass
spectrometry with verification by NMR for CP962 and CP985. Trypsin and
chymotrypsin inhibition assays confirmed the significance of the residue adjacent
to 3-amino-6-hydroxy-2-piperidone (Ahp) for the activity of the peptides.
Arginine-containing CPs (CPs-Arg2) inhibited trypsin at low IC50 values (0.24
0.26 µM) and showed mild activity against chymotrypsin (IC50 3.1-3.8
µM), while tyrosine-containing CPs (CPs-Tyr2) were selectively and potently
active against chymotrypsin (IC50 0.26 µM). No degradation of the peptides
was observed during the enzyme assays. Neither of the CPs were active against
thrombin, elastase or protein phosphatase 1. Two CPs (CP962 and CP985) had no
cytotoxic effects on MCF-7 breast cancer cells. Strong and selective activity of
the new cyanopeptolin variants makes them potential candidates for the
development of drugs against metabolic disorders and other diseases.
PMID- 29949854
TI - Modifiable Risk Factors for Common Ragweed (Ambrosia artemisiifolia) Allergy and
Disease in Children: A Case-Control Study.
AB - Ragweed allergy is a major public health concern. Within Europe, ragweed is an
introduced species and research has indicated that the amounts of ragweed pollen
are likely to increase over Europe due to climate change, with corresponding
increases in ragweed allergy. To address this threat, improving our understanding
of predisposing factors for allergic sensitisation to ragweed and disease is
necessary, specifically focusing upon factors that are potentially modifiable
(i.e., environmental). In this study, a total of 4013 children aged 2-13 years
were recruited across Croatia to undergo skin prick tests to determine
sensitisation to ragweed and other aeroallergens. A parental questionnaire
collected home environment, lifestyle, family and personal medical history, and
socioeconomic information. Environmental variables were obtained using
Geographical Information Systems and data from nearby pollen, weather, and air
pollution stations. Logistic regression was performed (clustered on school)
focusing on risk factors for allergic sensitisation and disease. Ragweed
sensitisation was strongly associated with ragweed pollen at levels over 5000
grains m-3 year−1 and, above these levels, the risk of sensitisation was 12
16 times greater than in low pollen areas with about 400 grains m-3 year−1.
Genetic factors were strongly associated with sensitisation but nearly all
potentially modifiable factors were insignificant. This included measures of
local land use and proximity to potential sources of ragweed pollen. Rural
residence was protective (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55
0.98), but the factors underlying this association were unclear. Being sensitised
to ragweed doubled (OR 2.17, 95% CI 1.59-2.96) the risk of rhinoconjunctivitis.
No other potentially modifiable risk factors were associated with
rhinoconjunctivitis. Ragweed sensitisation was strongly associated with ragweed
pollen, and sensitisation was significantly associated with rhinoconjunctivitis.
Apart from ragweed pollen levels, few other potentially modifiable factors were
significantly associated with ragweed sensitisation. Hence, strategies to lower
the risk of sensitisation should focus upon ragweed control.
PMID- 29949855
TI - Cholesterol-Lowering and Liver-Protective Effects of Cooked and Germinated Mung
Beans (Vigna radiata L.).
AB - We investigated the hypocholesterolemic and liver-protective effects of cooked
and germinated whole mung beans. Hamsters were fed for 28 days on diets rich in
saturated fatty acids and cholesterol, differing only in protein source (20%):
casein, cooked whole mung bean, and germinated mung bean. After 28 days, we found
reduced plasma concentrations of total cholesterol and non-HDL cholesterol,
increased faecal cholesterol excretion, and reduced levels of asparagine
aminotransferase and alanine aminotransferase enzymes in the liver. Reduction in
hepatic lipid deposition was observed between each of the mung bean groups
relative to the casein group. In addition, the animals of the geminated mung bean
group showed a lack of inflammatory infiltrate and better vascularisation of the
hepatic tissue. Results from this study show significant hypocholesterolemic and
liver-protective properties of the mung bean, which are further enhanced after
germination.
PMID- 29949856
TI - High Prevalence of Insufficient Vitamin D Intake and Serum 25-Hydroxyvitamin D in
Chinese School-Age Children: A Cross-Sectional Study.
AB - Despite the importance of vitamin D in early stages of life, data are lacking on
the levels of vitamin D intake and serum 25-hydroxyvitamin D (25-(OH)D) among
Chinese school-age children. The aims of this study were to investigate the
vitamin D intake and serum 25-(OH)D concentration of children aged 7 to 12 years
in China, and to measure the associations between vitamin D status and children's
growth and development parameters. We obtained data on vitamin D intake, serum 25
(OH)D concentration, and anthropometric measurements from a cross-sectional study
on school-aged children in China. Multiple linear regression and multivariable
logistic regression analyses assessed the associations mentioned above. A total
of 563 children (9.5 +/- 1.6 years) from six areas of China were included. Among
them, 86.1% had a vitamin D intake below the recommended nutrient intake (10
μg/day), and 54.7% had vitamin D deficiency (serum 25-(OH)D <15 ng/mL). We
also found that high vitamin D intake was inversely associated with the risk of
vitamin D deficiency (OR = 0.836, 95% confidence interval: 0.713, 0.980), and
serum 25-(OH)D concentration was positively associated with the intelligence
score and body mass index-for-age Z-score (BAZ) (p < 0.05). Insufficient vitamin
D intake and serum 25-(OH)D are prevalent among Chinese school-aged children. A
negative association was observed between vitamin D intake and the risk of
vitamin D deficiency. Moreover, vitamin D status was positively associated with
intelligence and BAZ, which await confirmation in future studies.
PMID- 29949857
TI - Inflammatory Markers and MicroRNAs: The Backstage Actors Influencing Prognosis in
Colorectal Cancer Patients.
AB - BACKGROUND: Colorectal cancer (CRC) remains a deadly disease, afflicting the
lives of millions worldwide. The prognosis of CRC patients is best predicted by
surgical resection and pathological analysis of specimens. Emerging evidence has
attributed a significant role to inflammatory markers and microRNAs (miRNAs) in
the prognosis and survival of CRC patients. AIM: Here, we review the literature
on inflammatory markers and miRNAs with an established role on survival rates,
response to systemic chemotherapy, and other clinic-pathological parameters in
CRC patients. RESULTS: Our literature review revealed a critical role of
inflammatory markers—specifically, the acute-phase proteins, inflammatory
cytokines, and blood cell ratios—on prognostic outcomes in CRC patients.
MiRNAs, on the other hand, were useful in predicting prognosis and clinical
response and accordingly stratifying CRC patients for optimal drug selection.
CONCLUSION: These biomarkers are easily measured in routine blood exams and can
be used in adjunct to the tumor-node-metastasis (TNM) staging system to identify
high-risk patients and those who are more likely to benefit from chemotherapy and
other targeted therapies. However, more prospective studies are needed for the
validation of these discussed prognostic and predictive biomarkers.
PMID- 29949859
TI - High Risk Blueberry Viruses by Region in North America; Implications for
Certification, Nurseries, and Fruit Production.
AB - There is limited information on the distribution of blueberry viruses in the U.S.
or around the world other than where the viruses were first discovered and
characterized. A survey for blueberry viruses was carried out in the U.S. in 2015
2017. Most blueberry viruses have been characterized to the point that sensitive
diagnostic assays have been developed. These assays are based on ELISA or
variations of PCR, which were employed here to determine the presence of
blueberry viruses in major blueberry production and nursery areas of the U.S. The
viruses included in this study were: blueberry fruit drop (BFDaV), blueberry
latent (BlLV), blueberry leaf mottle (BLMoV), blueberry mosaic (BlMaV), blueberry
red ringspot (BRRV), blueberry scorch (BlScV), blueberry shock (BlShV), blueberry
shoestring (BlSSV), blueberry virus A (BVA), peach rosette mosaic (PRMV), tobacco
ringspot (TRSV), and tomato ringspot (ToRSV). In the Pacific Northwest BlShV was
the most widespread virus, with BlScV and ToRSV detected in a limited number of
fields in Oregon and Washington, but BlScV was widespread in British Columbia. In
the upper midwest, the nematode-borne (ToRSV, TRSV), aphid-transmitted (BlSSV and
BVA) and pollen-borne (BLMoV) viruses were most widespread. In the northeast,
TRSV, ToRSV, and BlScV, were detected most frequently. In the southeast, BRRV and
BNRBV were the most widespread viruses. BlLV, a cryptic virus with no known
symptoms or effect on plant growth or yield was present in all regions. There are
other viruses present at low levels in each of the areas, but with the lower
incidence they pose minimal threat to nursery systems or fruit production. These
results indicate that there are hotspots for individual virus groups that
normally coincide with the presence of the vectors. The information presented
highlights the high risk viruses for nursery and fruit production each pose a
different challenge for control.
PMID- 29949858
TI - Role of Minimal (Measurable) Residual Disease Assessment in Older Patients with
Acute Myeloid Leukemia.
AB - Minimal (or measurable) residual (MRD) disease provides a biomarker of response
quality for which there is robust validation in the context of modern intensive
treatment for younger patients with Acute Myeloid Leukemia (AML). Nevertheless,
it remains a relatively unexplored area in older patients with AML. The lack of
progress in this field can be attributed to two main reasons. First, physicians
have a general reluctance to submitting older adults to intensive chemotherapy
due to their frailty and to the unfavourable biological disease profile
predicting a poor outcome following conventional chemotherapy. Second, with the
increasing use of low-intensity therapies (i.e., hypomethylating agents)
differing from conventional drugs in mechanism of action and dynamics of
response, there has been concomitant skepticism that these schedules can produce
deep hematological responses. Furthermore, age dependent differences in disease
biology also contribute to uncertainty on the prognostic/predictive impact in
older adults of certain genetic abnormalities including those validated for MRD
monitoring in younger patients. This review examines the evidence for the role of
MRD as a prognosticator in older AML, together with the possible pitfalls of MRD
evaluation in older age.
PMID- 29949860
TI - Mechanical Characterization of Gres Porcelain and Low-Velocity Impact Numerical
Modeling.
AB - The current investigation was conducted on gres porcelain stoneware, a robust,
impermeable and aesthetically pleasing type of ceramic mainly used for flooring,
characterizing its resistance to bending and low-velocity impact, both
representative efforts to which flooring tiles are constantly subjected as a
consequence of the fall of objects and microsubsidences. The mechanical
characterization was made through experimental tests following an adapted low
velocity impact testing routine, and the model was by validated numerical
simulation through the explicit code software LS-DYNA based on the Johnson
Holmquist constitutive material model. Specimens were tested before and after an
annealing cycle industrially used to allow porcelain folding. The thermal
treatment demonstrated to infer a decrease in mechanical resistance on the
material, understood as a consequence of its elevated maximum temperature and
fast cooling rate. The numerical model calibrated successfully allows predicting
the behavior of gres porcelain before and after annealing against low-velocity
impact.
PMID- 29949861
TI - Lessons and Guidance from the Special Issue on Electronic Cigarette Use and
Public Health.
PMID- 29949862
TI - Mesoporous Silicon Particles Favor the Induction of Long-Lived Humoral Responses
in Mice to a Peptide-Based Vaccine.
AB - Vaccinology faces the challenge of developing improved immunization approaches
that are able to induce long-term immunity with the desired Th profile according
to the pathology. In this context, new vehicles for efficient antigen delivery
that exert adjuvant effects play a critical role in addressing this goal. Herein,
mesoporous silicon particles (PSiP) were assessed as carriers for a peptide-based
vaccine targeting the receptor for advanced glycation end products (RAGE), which
is a relevant receptor in Alzheimer´s disease and other diseases. A RAGE
peptide was adsorbed onto PSiP (PSiP vaccine) and administered to BALB/c mice,
leading to immune responses that were similar in magnitude to those induced by
the soluble peptide. However, the response induced by PSiP lasted for a
significantly longer period when compared with the behavior of the group
immunized with the peptide alone. Therefore, PSiP are proposed as carriers to
enhance immune memory, which is critical in vaccination. This study opens
interesting perspectives related to the application of PSiP in vaccinology.
PMID- 29949863
TI - Predictors of Urinary Arsenic Levels among Postmenopausal Danish Women.
AB - Arsenic is a risk factor for several noncommunicable diseases, even at low doses.
Urinary arsenic (UAs) concentration is a good biomarker for internal dose, and
demographic, dietary, and lifestyle factors are proposed predictors in
nonoccupationally exposed populations. However, most predictor studies are
limited in terms of size and number of predictors. We investigated demographic,
dietary, and lifestyle determinants of UAs concentrations in 744 postmenopausal
Danish women who had UAs measurements and questionnaire data on potential
predictors. UAs concentrations were determined using mass spectrometry (ICP-MS),
and determinants of the concentration were investigated using univariate and
multivariate regression models. We used a forward selection procedure for model
optimization. In all models, fish, alcohol, and poultry intake were associated
with higher UAs concentration, and tap water, fruit, potato, and dairy intake
with lower concentration. A forward regression model explained 35% (R2) of the
variation in concentrations. Age, smoking, education, and area of residence did
not predict concentration. The results were relatively robust across sensitivity
analyses. The study suggested that UAs concentration in postmenopausal women was
primarily determined by dietary factors, with fish consumption showing the
strongest direct association. However, the majority of variation in UAs
concentration in this study population is still unexplained.
PMID- 29949864
TI - New Insights on the Photodegradation of Caffeine in the Presence of Bio-Based
Substances-Magnetic Iron Oxide Hybrid Nanomaterials.
AB - The exploitation of organic waste as a source of bio-based substances to be used
in environmental applications is gaining increasing interest. In the present
research, compost-derived bio-based substances (BBS-Cs) were used to prepare
hybrid magnetic nanoparticles (HMNPs) to be tested as an auxiliary in advanced
oxidation processes. Hybrid magnetic nanoparticles can be indeed recovered at the
end of the treatment and re-used in further water purification cycles. The
research aimed to give new insights on the photodegradation of caffeine, chosen
as marker of anthropogenic pollution in natural waters, and representative of the
contaminants of emerging concern (CECs). Hybrid magnetic nanoparticles were
synthetized starting from Fe(II) and Fe(III) salts and BBS-C aqueous solution, in
alkali medium, via co-precipitation. Hybrid magnetic nanoparticles were
characterized via X-ray diffraction (XRD), thermo-gravimetric analysis (TGA) and
Fourier transform infrared (FTIR) spectroscopy. The effect of pH, added hydrogen
peroxide, and dissolved oxygen on caffeine photodegradation in the presence of
HMNPs was assessed. The results allow for the hypothesis that caffeine abatement
can be obtained in the presence of HMNPs and hydrogen peroxide through a
heterogeneous photo-Fenton mechanism. The role of hydroxyl radicals in the
process was assessed examining the effect of a selective hydroxyl radical
scavenger on the caffeine degradation kinetic.
PMID- 29949866
TI - Effect of Shear Stress on Isothermal Crystallization Behavior of CaO-Al2O3-SiO2
Na2O-CaF2 Slags.
AB - How to coordinate the contradiction between lubrication and heat transfer in the
peritectic steel casting process is the key technical difficulty in preparing
mold fluxes. The mold fluxes that are required for casting are subjected to the
shear stress generated by mold oscillation and slab movement, which affects the
crystallization performance of slags. The quantitative effect of slags’
crystallization performance by shear stress is studied to develop a low-basicity
and high-crystallization mold flux to solve the above problem. The results show
that the crystallization kinetic condition is promoted, and the crystallization
activation energy is reduced by the shear stress, which leads to an increase in
the crystallization temperature. Concurrently, the crystal size is reduced.
However, the shear stress has no effect on the crystalline phase. The influence
of different shear stresses on the crystallization ability of molten slags is
related to the crystal nucleation and growth mechanisms. The crystalline fraction
of the slag films at 300 rpm (69 s−1) is 44.7%, which is an increase of
17.7% compared with the crystalline fraction of the slag films at 200 rpm (46
s−1). Moreover, the shear stress has little effect on the lubricating
properties of the mold fluxes, although the crystallization ability is promoted
by the agitation.
PMID- 29949865
TI - Donor Site Location Is Critical for Proliferation, Stem Cell Capacity, and
Osteogenic Differentiation of Adipose Mesenchymal Stem/Stromal Cells:
Implications for Bone Tissue Engineering.
AB - Human adipose mesenchymal stem/stromal cells (Ad-MSCs) have been proposed as a
suitable option for bone tissue engineering. However, donor age, weight, and
gender might affect the outcome. There is still a lack of knowledge of the
effects the donor tissue site might have on Ad-MSCs function. Thus, this study
investigated proliferation, stem cell, and osteogenic differentiation capacity of
human Ad-MSCs obtained from subcutaneous fat tissue acquired from different
locations (abdomen, hip, thigh, knee, and limb). Ad-MSCs from limb and knee
showed strong proliferation despite the presence of osteogenic stimuli, resulting
in limited osteogenic characteristics. The less proliferative Ad-MSCs from hip
and thigh showed the highest alkaline phosphatase (AP) activity and matrix
mineralization. Ad-MSCs from the abdomen showed good proliferation and osteogenic
characteristics. Interestingly, the observed differences were not dependent on
donor age, weight, or gender, but correlated with the expression of Sox2, Lin28A,
Oct4α, and Nanog. Especially, low basal Sox2 levels seemed to be pivotal
for osteogenic differentiation. Our data clearly show that the donor tissue site
affects the proliferation and osteogenic differentiation of Ad-MSCs
significantly. Thus, for bone tissue engineering, the donor site of the adipose
tissue from which the Ad-MSCs are derived should be adapted depending on the
requirements, e.g., cell number and differentiation state.
PMID- 29949867
TI - Correction: Martinez-Gonzalez, M.A. et al. Transferability of the Mediterranean
Diet to Non-Mediterranean Countries. What Is and What Is Not the Mediterranean
Diet. Nutrients 2017, 9, 1226.
AB - The authors have requested that the following changes be made to their
paper[...].
PMID- 29949868
TI - Circular Dichroism in Fluorescence Emission Following the C 1s->pi* Excitation
and Resonant Auger Decay of Carbon Monoxide.
AB - Dichroism in angle-resolved spectra of circularly polarized fluorescence from
freely-rotating CO molecules was studied experimentally and theoretically. For
this purpose, carbon monoxide in the gas phase was exposed to circularly
polarized soft X-ray synchrotron radiation. The photon energy was tuned across
the C 1s→π* resonant excitation, which decayed via the participator Auger
transition into the CO+ A 2Π state. The dichroic parameter β1 of the
subsequent CO+ (A 2Π → X 2Σ+) visible fluorescence was measured by
photon-induced fluorescence spectroscopy. Present experimental results are
explained with the ab initio electronic structure and dynamics calculations
performed by the single center method. Our results confirm the possibility to
perform partial wave analysis of the emitted photoelectrons in closed-shell
molecules.
PMID- 29949869
TI - PPARs and Energy Metabolism Adaptation during Neurogenesis and Neuronal
Maturation.
AB - Peroxisome proliferator activated receptors (PPARs) are a class of ligand
activated transcription factors, belonging to the superfamily of receptors for
steroid and thyroid hormones, retinoids, and vitamin D. PPARs control the
expression of several genes connected with carbohydrate and lipid metabolism, and
it has been demonstrated that PPARs play important roles in determining neural
stem cell (NSC) fate. Lipogenesis and aerobic glycolysis support the rapid
proliferation during neurogenesis, and specific roles for PPARs in the control of
different phases of neurogenesis have been demonstrated. Understanding the
changes in metabolism during neuronal differentiation is important in the context
of stem cell research, neurodegenerative diseases, and regenerative medicine. In
this review, we will discuss pivotal evidence that supports the role of PPARs in
energy metabolism alterations during neuronal maturation and neurodegenerative
disorders.
PMID- 29949870
TI - Development of a Cumulative Exposure Index (CEI) for Manganese and Comparison
with Bone Manganese and Other Biomarkers of Manganese Exposure.
AB - Manganese (Mn) exposure can result in parkinsonism. However, understanding of
manganese neurotoxicity has been limited by the lack of a cumulative Mn
biomarker. Therefore, the current goal was to develop Mn cumulative exposure
indices (MnCEI), an established method to estimate cumulative exposure, and
determine associations of MnCEI with blood Mn (BMn), fingernail Mn (FMn), and
bone Mn (BnMn). We completed a cross-sectional study of 60 male Chinese workers.
Self-reported occupational history was used to create two MnCEIs reflecting the
previous 16 years (MnCEI16) and total work history (MnCEITOT). An in vivo neutron
activation analysis system was used to quantify BnMn. BMn and FMn were measured
using ICP-MS. Mean (standard deviation) MnCEITOT and MnCEI16 were 37.5 (22.0) and
25.0 (11.3), respectively. Median (interquartile range) BMn, FMn, and BnMn were
14.1 (4.0) μg/L, 13.5 (58.5) μg/g, and 2.6 (7.2) μg/g dry bone,
respectively. MnCEI16 was significantly correlated with FMn (Spearman’s
ρ = 0.44; p = 0.02), BnMn (ρ = 0.44; p < 0.01), and MnCEITOT (ρ =
0.44; p < 0.01). In adjusted regression models, MnCEI16 was significantly
associated with BnMn (β = 0.03; 95% confidence interval = 0.001, 0.05); no
other biomarkers were associated with MnCEI. This suggests BnMn may be a useful
biomarker of the previous 16 years of Mn exposure, but larger studies are
recommended.
PMID- 29949871
TI - Single Chip-Based Nano-Optomechanical Accelerometer Based on Subwavelength
Grating Pair and Rotated Serpentine Springs.
AB - Optical coupling between subwavelength grating pairs allows for the precise
measurement of lateral or vertical displacement of grating elements and gives
rise to different types of displacement and inertial sensors. In this paper, we
demonstrate a design for a nano-optomechanical accelerometer based on a
subwavelength grating pair that can be easily fabricated by a single Silicon-on
insulator (SOI) chip. The parameters of the subwavelength grating pair-based
optical readout, including period, duty cycle, thickness of grating and metal
film, and the distance of the air gap, were optimized by combining a genetic
algorithm and rigorous coupled wavelength analysis (RCWA) to obtain the optimal
sensitivity to the displacement of suspended grating element and the
acceleration. A corresponding mechanical design was also completed to meet the
highly sensitive acceleration measurement requirement while considering the
mechanical cross-axis sensitivity, dynamic range, bandwidth, and fabrication
feasibility. This device was verified by both RCWA and finite-different-time
domain methods, and a tolerance analysis was also completed to confirm that it is
able to achieve the extremely high optical displacement sensitivity of 1.8%/nm,
acceleration-displacement sensitivity of 1.56 nm/mg, and acceleration measurement
sensitivity of more than 2.5%/mg, which is almost one order of magnitude higher
than any reported counterparts. This work enables a single SOI-based high
performance accelerometer, and provides a theoretical basis and fabrication
guides for the design.
PMID- 29949872
TI - Using microRNA Networks to Understand Cancer.
AB - Human cancers are characterized by deregulated expression of multiple microRNAs
(miRNAs), involved in essential pathways that confer the malignant cells their
tumorigenic potential. Each miRNA can regulate hundreds of messenger RNAs
(mRNAs), while various miRNAs can control the same mRNA. Additionally, many
miRNAs regulate and are regulated by other species of non-coding RNAs, such as
circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs). For this reason, it
is extremely difficult to predict, study, and analyze the precise role of a
single miRNA involved in human cancer, considering the complexity of its
connections. Focusing on a single miRNA molecule represents a limited approach.
Additional information could come from network analysis, which has become a
common tool in the biological field to better understand molecular interactions.
In this review, we focus on the main types of networks (monopartite, association
networks and bipartite) used for analyzing biological data related to miRNA
function. We briefly present the important steps to take when generating
networks, illustrating the theory with published examples and with future
perspectives of how this approach can help to better select miRNAs that can be
therapeutically targeted in cancer.
PMID- 29949873
TI - Effects of Synbiotics among Constipated Adults in Serdang, Selangor, Malaysia-A
Randomised, Double-Blind, Placebo-Controlled Trial.
AB - Synbiotics approach complementarily and synergistically toward the balance of
gastrointestinal microbiota and improvement in bowel functions. A randomised,
double-blind, placebo-controlled study was conducted to examine the effects of a
synbiotics supplement among constipated adults. A total of 85 constipated adults,
diagnosed by Rome III criteria for functional constipation were randomised to
receive either synbiotics (n = 43) or placebo (n = 42) once daily (2.5 g) in the
morning for 12 weeks. Eight times of follow-up was conducted every fortnightly
with treatment response based on a questionnaire that included a record of
evacuation (stool frequency, stool type according to Bristol Stool Form Scale),
Patients Assessment on Constipation Symptoms (PAC-SYM), and Patients Assessment
on Constipation Quality of Life (PAC-QOL). There were no significant differences
in stool evacuation, but defecation frequency and stool type in treatment group
were improved tremendously than in placebo group. While the treatment group was
reported to have higher reduction in severity of functional constipation
symptoms, the differences were not statistically significant. Dietary
supplementation of synbiotics in this study suggested that the combination of
probiotics and prebiotics improved the functional constipation symptoms and
quality of life although not significant. This was due to the high placebo effect
which synbiotics failed to demonstrate benefit over the controls.
PMID- 29949874
TI - The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy
Resistance, and Phosphorylation of GSK-3beta in Pancreatic Cancer.
AB - Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related death, and
personalized targeted cancer therapy is becoming a promising treatment strategy
for PaCa. The central approach of targeted therapy is to find a targetable key
and an effective targeting method. In this study, the importance of GPRC5a (the G
protein-coupled receptor family C, member 5, group A) was identified using data
mining methods based on published datasets. After analysis of the basic
expression of GPRC5a in normal pancreas tissue and various PaCa cell lines, gene
editing of GPRC5a in the human PaCa cell line MIA PaCa-2 and the mouse PaCa cell
line TB32047 was performed using CRISPR/Cas9 (Clustered Regularly Interspaced
Short Palindromic Repeats/CRISPR-associated proteins 9) to investigate the
influence of GPRC5a on the proliferation and migration of PaCa cells as well as
its effects on chemotherapy drug resistance. The results showed that GPRC5a was
upregulated in PaCa tissues and various PaCa cell lines. Knockout of GPRC5a
reduced the proliferation and migration ability of PaCa cell lines and suppressed
the chemotherapy drug resistance of gemcitabine, oxaliplatin, and fluorouracil in
PaCa cells. The phosphorylation of GSK-3β (Glycogen synthase kinase-3β)
was found to be upregulated in the MIA PaCa-2 and TB32047 cells after GPRC5a
knockout. In conclusion, GPRC5a was upregulated in PaCa leading to an enhanced
drug resistance in PaCa cells. These results provide for the first time a
theoretical basis for the development of an improved PaCa targeted therapy.
PMID- 29949875
TI - Solution-Grown Dendritic Pt-Based Ternary Nanostructures for Enhanced Oxygen
Reduction Reaction Functionality.
AB - Nanoalloys with anisotropic morphologies of branched and porous internal
structures show great promise in many applications as high performance materials.
Reported synthetic approaches for branched alloy nanostructures are, however,
limited by the synthesis using a seed-growth process. Here, we demonstrate a
conveniently fast and one-pot solution-phase thermal reduction strategy yielding
nanoalloys of Pt with various solute feed ratios, exhibiting hyperbranched
morphologies and good dispersity. When Pt was alloyed with transition metals (Ni,
Co, Fe), we observed well-defined dendritic nanostructures in PtNi, PtCo and
Pt(NiCo), but not in PtFe, Pt(FeNi) or Pt(FeCo) due to the steric hindrance of
the trivalent Fe(acac)3 precursor used during synthesis. In the case of Pt-based
nanoalloys containing Ni and Co, the dendritic morphological evolution observed
was insensitive to large variations in solute concentration. The functionality of
these nanoalloys towards the oxygen reduction reaction (ORR); however, was
observed to be dependent on the composition, increasing with increasing solute
content. Pt3(NiCo)2 exhibited superior catalytic activity, affording about a five
and 10-fold enhancement in area-specific and mass-specific catalytic activities,
respectively, compared to the standard Pt/C nanocatalyst. This solution-based
synthetic route offers a new approach for constructing dendritic Pt-based
nanostructures with excellent product yield, monodispersity and high
crystallinity.
PMID- 29949876
TI - Phenotypic Variation during Biofilm Formation: Implications for Anti-Biofilm
Therapeutic Design.
AB - Various bacterial species cycle between growth phases and biofilm formation, of
which the latter facilitates persistence in inhospitable environments. These
phases can be generally characterized by one or more cellular phenotype(s), each
with distinct virulence factor functionality. In addition, a variety of
phenotypes can often be observed within the phases themselves, which can be
dependent on host conditions or the presence of nutrient and oxygen gradients
within the biofilm itself (i.e., microenvironments). Currently, most anti-biofilm
strategies have targeted a single phenotype; this approach has driven effective,
yet incomplete, protection due to the lack of consideration of gene expression
dynamics throughout the bacteria’s pathogenesis. As such, this article
provides an overview of the distinct phenotypes found within each biofilm
development phase and demonstrates the unique anti-biofilm solutions each phase
offers. However, we conclude that a combinatorial approach must be taken to
provide complete protection against biofilm forming bacterial and their resulting
diseases.
PMID- 29949877
TI - Properties, Preparation and Applications of Low Dimensional Transition Metal
Dichalcogenides.
AB - Low-dimensional layered transition metal dichalcogenides (TMDs) have recently
emerged as an important fundamental research material because of their unique
structural, physical and chemical properties. These novel properties make these
TMDs a suitable candidate in numerous potential applications. In this review, we
briefly summarize the properties of low-dimensional TMDs, and then focus on the
various methods used in their preparation. The use of TMDs in electronic devices,
optoelectronic devices, electrocatalysts, biosystems, and hydrogen storage is
also explored. The cutting-edge future development probabilities of these
materials and numerous research challenges are also outlined in this review.
PMID- 29949878
TI - Novel Applications of OnabotulinumtoxinA in Lower Urinary Tract Dysfunction.
AB - OnabotulinumtoxinA (BoNT-A) was first used to treat neurogenic lower urinary
tract dysfunction (LUTD) 30 years ago. Recently, application of BoNT-A in LUTD
have become more common since the approval of intravesical BoNT-A injection for
patients with both overactive bladders (OAB) and neurogenic detrusor overactivity
(NDO) by regulatory agencies in many countries. Although unlicensed, BoNT-A has
been recommended to treat patients with interstitial cystitis/bladder pain
syndrome (IC/BPS) under different guidelines. BoNT-A delivery with liposome
encapsulation and gelation hydrogel intravesical instillation provided a
potentially less invasive and more convenient form of application for patients
with OAB or IC/BPS. BoNT-A injections into the urethral sphincter for spinal cord
injury patients with detrusor-sphincter dyssynergia have been used for a long
time. New evidence revealed that it could also be applied to patients with non
neurogenic dysfunctional voiding. Previous studies and meta-analyses suggest that
BoNT-A injections for patients with benign prostate hyperplasia do not have a
better therapeutic effect than placebo. However, new randomized and placebo
controlled trials revealed intraprostatic BoNT-A injection is superior to placebo
in specific patients. A recent trial also showed intraprostatic BoNT-A injection
could significantly reduce pain in patients with chronic prostatitis. Both
careful selection of patients and prudent use of urodynamic evaluation results to
confirm diagnoses are essential for successful outcomes of BoNT-A treatment for
LUTD.
PMID- 29949879
TI - PPARgamma Expression Is Diminished in Macrophages of Recurrent Miscarriage
Placentas.
AB - PPARγ belongs to the group of nuclear receptors which is expressed in the
trophoblast and together with other factors is responsible for the maintenance of
pregnancy. Apart from that PPARγ is also a main factor for macrophage
polarization. The aim of this study was to investigate the combined expression
pattern and frequency of PPARγ under physiological circumstances and in
spontaneous and recurrent miscarriages in the trophoblast and in maternal
macrophages of the decidua. Human placental tissues of the first trimester (15
physiologic pregnancies, 15 spontaneous abortion and 16 recurrent miscarriage
placentas) were analyzed for expression of the nuclear receptor PPARγ.
Expression changes were evaluated by immunohistochemistry and real time PCR (RT
PCR) in trophoblast and in maternal macrophages of the decidua. Maternal
macrophages were identified by double immunofluorescence using cluster of
differentiation 68 (CD68) as marker for macrophages and further characterized
regarding their M1/M2 polarization status. The intermediate villous trophoblast
revealed a significantly lower PPARγ expression in spontaneous and
recurrent abortion. Maternal macrophages express PPARγ. Their number is
significantly enhanced in the decidua of spontaneous miscarriages whereas in
recurrent miscarriages maternal macrophages seem to express PPARγ only in
very few cases. PPARγ is associated with an M2 polarization state that is
common for decidual macrophages. The lack of PPARγ in recurrent miscarriage
decidual macrophages seems to be associated with a specific inflammatory response
against the fetus.
PMID- 29949880
TI - Somatostatin Receptors as Molecular Targets in Human Uveal Melanoma.
AB - Uveal melanoma (UM) is the most common primary intraocular malignancy in adults,
with an incidence of 4-5 cases per million. The prognosis of UM is very poor. In
the present study, our aim was to investigate the expression of mRNA and protein
for somatostatin receptor types-1, -2, -3, -4, -5 (SSTR-1-5) in human UM tissue
samples and in OCM-1 and OCM-3 human UM cell lines by qRT-PCR, western blot and
ligand competition assay. The mRNA for SSTR-2 showed markedly higher expression
in UM tissues than SSTR-5. The presence of SSTRs was demonstrated in 70% of UM
specimens using ligand competition assay and both human UM models displayed
specific high affinity SSTRs. Among the five SSTRs, the mRNA investigated for
SSTR-2 and SSTR-5 receptors was strongly expressed in both human UM cell lines,
SSTR-5 showing the highest expression. The presence of the SSTR-2 and SSTR-5
receptor proteins was confirmed in both cell lines by western blot. In summary,
the expression of somatostatin receptors in human UM specimens and in OCM-1 and
OCM-3 human UM cell lines suggests that they could serve as a potential molecular
target for therapy of UM using modern powerful cytotoxic SST analogs targeting
SSTR-2 and SSTR-5 receptors.
PMID- 29949881
TI - Efficient Intracellular Delivery of Cell-Impermeable Cargo Molecules by Peptides
Containing Tryptophan and Histidine.
AB - We have previously evaluated and reported numerous classes of linear and cyclic
peptides containing hydrophobic and hydrophilic segments for intracellular
delivery of multiple molecular cargos. Herein, a combination of histidine and
tryptophan amino acids were designed and evaluated for their efficiency in
intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug,
emtricitabine. Two new decapeptides, with linear and cyclic natures, both
containing alternate tryptophan and histidine residues, were synthesized using
Fmoc/tBu solid-phase chemistry. The peptides were characterized and purified by
using matrix-assisted laser desorption/ionization (MALDI) spectroscopy and high
performance liquid chromatography (HPLC), respectively. These peptides did not
show significant toxicity up to 100 µM in ovarian cancer (SK-OV-3) and
leukemia cancer (CCRF-CEM) cells. Furthermore, the cellular uptake of a
fluorescence (F’)-labeled cell-impermeable phosphopeptide (F’-GpYEEI)
was enhanced in the presence of linear (WH)5 and cyclic [WH]5 by 2- and 8-fold,
respectively, compared to the uptake of the phosphopeptide alone. The cellular
uptake was not significantly changed in the presence of endocytosis inhibitors.
Furthermore, the intracellular uptake of the fluorescently-labeled anti-HIV drug,
emtricitabine (F’-FTC), by linear (WH)5 and cyclic [WH]5 in SK-OV-3 cancer
cell lines was found to be enhanced by 3.5- and 9-fold, respectively, compared to
that of the drug alone. Fluorescent uptake experiments confirmed the localization
of F’-GpYEEI-loaded cyclic [WH]5 intracellularly in the SK-OV-3 cancer cell
line after 3 h of incubation. Thus, these data demonstrated that [WH]5 containing
tryptophan and histidine enhanced the cellular uptake of F’-GpYEEI and
emtricitabine.
PMID- 29949883
TI - In Situ Investigation of the Iron Carbide Precipitation Process in a Fe-C-Mn-Si
Q&P Steel.
AB - Quenching and Partitioning (Q&P) steels are promising candidates for automotive
applications because of their lightweight potential. Their properties depend on
carbon enrichment in austenite which, in turn, is strongly influenced by carbide
precipitation in martensite during quenching and partitioning treatment. In this
paper, by coupling in situ High Energy X-Ray Diffraction (HEXRD) experiments and
Transmission Electron Microscopy (TEM), we give some clarification regarding the
precipitation process of iron carbides in martensite throughout the Q&P process.
For the first time, precipitation kinetics was followed in real time. It was
shown that precipitation starts during the reheating sequence for the steel
studied. Surprisingly, the precipitated fraction remains stable all along the
partitioning step at 400 °C. Furthermore, the analyses enable the conclusion
that the iron carbides are most probably eta carbides. The presence of cementite
was ruled out, while the presence of several epsilon carbides cannot be strictly
excluded.
PMID- 29949884
TI - Syntheses, Crystal Structures, and Antitumor Activities of Copper(II) and
Nickel(II) Complexes with 2-((2-(Pyridin-2-yl)hydrazono)methyl)quinolin-8-ol.
AB - Two transition metal complexes with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin
8-ol (L), [Cu(L)Cl2]2 (1) and [Ni(L)Cl2]·CH2Cl2 (2), were synthesized and
fully characterized. Complex 1 exhibited high in vitro antitumor activity against
SK-OV-3, MGC80-3 and HeLa cells with IC50 values of 3.69 +/- 0.16, 2.60 +/- 0.17,
and 3.62 +/- 0.12 μM, respectively. In addition, complex 1 caused cell arrest
in the S phase, which led to the down-regulation of Cdc25 A, Cyclin B, Cyclin A,
and CDK2, and the up-regulation of p27, p21, and p53 proteins in MGC80-3 cells.
Complex 1 induced MGC80-3 cell apoptosis via a mitochondrial dysfunction pathway,
as shown by the significantly decreased level of bcl-2 protein and the loss of
Δψ, as well as increased levels of reactive oxygen species (ROS),
intracellular Ca2+, cytochrome C, apaf-1, caspase-3, and caspase-9 proteins in
MGC80-3 cells.
PMID- 29949882
TI - MicroRNAs as Potential Biomarkers in Merkel Cell Carcinoma.
AB - Merkel cell carcinoma (MCC) is a rare and aggressive type of skin cancer
associated with a poor prognosis. This carcinoma was named after its presumed
cell of origin, the Merkel cell, which is a mechanoreceptor cell located in the
basal epidermal layer of the skin. Merkel cell polyomavirus seems to be the major
causal factor for MCC because approximately 80% of all MCCs are positive for
viral DNAs. UV exposure is the predominant etiological factor for virus-negative
MCCs. Intracellular microRNA analysis between virus-positive and virus-negative
MCC cell lines and tumor samples have identified differentially expressed
microRNAs. Comparative microRNA profiling has also been performed between MCCs
and other non-MCC tumors, but not between normal Merkel cells and malignant
Merkel cells. Finally, Merkel cell polyomavirus encodes one microRNA, but its
expression in virus-positive MCCs is low, or non-detectable or absent,
jeopardizing its biological relevance in tumorigenesis. Here, we review the
results of microRNA studies in MCCs and discuss the potential application of
microRNAs as biomarkers for the diagnosis, progression and prognosis, and
treatment of MCC.
PMID- 29949885
TI - Antimicrobial Potential and Cytotoxicity of Silver Nanoparticles Phytosynthesized
by Pomegranate Peel Extract.
AB - The phytosynthesis of metal nanoparticles is nowadays attracting the increased
attention of researchers and is much needed given the worldwide matter related to
environmental contamination. The antimicrobial activity of colloidal and spray
formulation of silver nanoparticles (AgNPs) synthesized by pomegranate peel
extract against Candida albicans and Staphylococcus aureus, and their
cytotoxicity in mammalian cells were tested in the present study. Dry matter, pH,
total phenolics, and ellagic acid in the extract were determined. Then, AgNPs
were phytosynthesized and characterized by X-ray diffraction, electron
transmission microscopy, dynamic light scattering, zeta potential, and Ag+
dosage. Spray formulations and respective chemical-AgNP controls were prepared
and tested. The peel extract reduced more than 99% of Ag+, and produced
nanoparticles with irregular forms and an 89-nm mean size. All AgNP presented
antimicrobial activity, and the spray formulation of green-AgNP increased by 255
and 4 times the effectiveness against S. aureus and C. albicans, respectively.
The cytotoxicity of colloidal and spray green-AgNP was expressively lower than
the respective chemical controls. Pomegranate peel extract produced stable AgNP
with antimicrobial action and low cytotoxicity, stimulating its use in the
biomedical field.
PMID- 29949886
TI - Beverage Consumption Patterns among Infants and Young Children (0-47.9 Months):
Data from the Feeding Infants and Toddlers Study, 2016.
AB - (1) Background: Data about early life beverage intake patterns is sparse. We
describe beverage patterns among infants and young children from the Feeding
Infants and Toddlers Study (FITS) 2016. (2) Methods: FITS 2016 is a cross
sectional survey of U.S. parents/caregivers of children 0-47.9 months (n = 3235).
Food and beverage intakes were collected by 24-h dietary recalls to describe
beverage consumption patterns including: a) prevalence of consumption, per capita
and per consumer intake, b) contribution to intake of calories and key nutrients,
and c) prevalence according to eating occasions. (3) Results: Breast milk and
infant formula were commonly consumed among <12-month-olds. Among 12-23.9-month
olds, the most commonly consumed beverage was whole milk (67% consuming),
followed by 100% juice (50% consuming). Plain drinking water was consumed by 70%
of 12-23.9-month-olds and 78% of 24-47.9-month-olds. Among 12-47.9-month-olds,
milks provided more energy and key nutrients than all other beverages. Across
eating occasions, sugar-sweetened beverage (SSB) consumption, especially in the
form of fruit-flavored drinks, was higher among 24-47.9 compared to 12-23.9-month
olds. Only 23-32% of ≥12-month-olds consumed milk or water at lunch or dinner.
(4) Conclusions: Opportunities exist to improve beverage patterns. Future
interventions may benefit from focusing on timely introduction of age-appropriate
beverages and reducing consumption of SSBs.
PMID- 29949888
TI - Carbonate Apatite Nanoparticles-Facilitated Intracellular Delivery of siRNA(s)
Targeting Calcium Ion Channels Efficiently Kills Breast Cancer Cells.
AB - Specific gene knockdown facilitated by short interfering RNA (siRNA) is a
potential approach for suppressing the expression of ion channels and transporter
proteins to kill breast cancer cells. The overexpression of calcium ion channels
and transporter genes is seen in the MCF-7 breast cancer cell line. Since naked
siRNA is anionic and prone to nuclease-mediated degradation, it has limited
permeability across the cationic cell membrane and short systemic half-life,
respectively. Carbonate apatite (CA) nanoparticles were formulated,
characterized, loaded with a series of siRNAs, and delivered into MCF-7 and 4T1
breast cancer cells to selectively knockdown the respective calcium and magnesium
ion channels and transporters. Individual knockdown of TRPC6, TRPM7, TRPM8,
SLC41A1, SLC41A2, ORAI1, ORAI3, and ATP2C1 genes showed significant reduction (p
< 0.001) in cell viability depending on the cancer cell type. From a variety of
combinations of siRNAs, the combination of TRPC6, TRPM8, SLC41A2, and MAGT1
siRNAs delivered via CA produced the greatest cell viability reduction, resulting
in a cytotoxicity effect of 57.06 +/- 3.72% (p < 0.05) and 59.83 +/- 2.309% (p =
0.09) in 4T1 and MCF-7 cell lines, respectively. Some of the combinations were
shown to suppress the Akt pathway in Western Blot analysis when compared to the
controls. Therefore, CA-siRNA-facilitated gene knockdown in vitro holds a high
prospect for deregulating cell proliferation and survival pathways through the
modulation of Ca2+ signaling in breast cancer cells.
PMID- 29949887
TI - FGF Family: From Drug Development to Clinical Application.
AB - Fibroblast growth factor (FGF) belongs to a large family of growth factors. FGFs
use paracrine or endocrine signaling to mediate a myriad of biological and
pathophysiological process, including angiogenesis, wound healing, embryonic
development, and metabolism regulation. FGF drugs for the treatment of burn and
ulcer wounds are now available. The recent discovery of the crucial roles of the
endocrine-acting FGF19 subfamily in maintaining homeostasis of bile acid,
glucose, and phosphate further extended the activity profile of this family.
Here, the applications of recombinant FGFs for the treatment of wounds, diabetes,
hypophosphatemia, the development of FGF receptor inhibitors as anti-neoplastic
drugs, and the achievements of basic research and applications of FGFs in China
are reviewed.
PMID- 29949889
TI - Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration,
Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo
Controlled Study.
AB - Collagen-peptide supplementation could be an effective remedy to improve
hydration, elasticity, and wrinkling in human skin. The aim of this study was to
conduct a double-blind, randomized, placebo-controlled trial to clinically
evaluate the effect on human skin hydration, wrinkling, and elasticity of Low
molecular-weight Collagen peptide (LMWCP) with a tripetide (Gly-X-Y) content >15%
including 3% Gly-Pro-Hyp. Individuals (n = 64) were randomly assigned to receive
either placebo or 1000 mg of LMWCP once daily for 12 weeks. Parameters of skin
hydration, wrinkling, and elasticity were assessed at baseline and after 6 weeks
and 12 weeks. Compared with the placebo group, skin-hydration values were
significantly higher in the LMWCP group after 6 weeks and 12 weeks. After 12
weeks in the LMWCP group, visual assessment score and three parameters of skin
wrinkling were significantly improved compared with the placebo group. In case of
skin elasticity, one parameter out of three was significantly improved in the
LMWCP group from the baseline after 12 weeks, while, compared with the placebo
group, two parameters out of three in the LMWCP group were higher with
significance after 12 weeks. In terms of the safety of LMWCP, none of the
subjects presented adverse symptoms related to the test material during the study
period. These results suggest that LMWCP can be used as a health functional food
ingredient to improve human skin hydration, elasticity, and wrinkling.
PMID- 29949890
TI - The Pattern of Complementary Foods in American Infants and Children Aged 0-5
Years Old-A Cross-Sectional Analysis of Data from the NHANES 2011-2014.
AB - Proper nutrition early in life can influence children’s present and future
health. While several authoritative sources provide eating/food recommendations,
only a few studies have assessed whether these recommendations are followed. The
goal of this paper was to examine food and nutrient intakes on any given day
during infancy and early childhood among various ethnicities. Twenty-four-hour
dietary recall data of 0-5 years-old children (n = 2431) from the National Health
and Nutrition Examination Survey (NHANES) 2011-2014 was used to estimate intakes
of nutrients and food groups and prevalence of inadequate intake. Data was
analyzed separately for various age groups and ethnicities, and differences in
means by age and or race/ethnicity were determined by t-tests with p < 0.05 as
significant. The results indicate that intakes of all food groups were expectedly
low at 0-11 months, increased with age, and were influenced by race/ethnicity.
Mixed dish consumption, which also increased with age, made substantial
contributions to children’s food group intakes. However, there was a
substantial percentage of the population among all age and race/ethnic groups who
did not consume the recommended amounts for each food group and had inadequate
intakes of key nutrients, such as calcium, vitamin D, and vitamin E. Non-Hispanic
black children consumed less dairy and more protein foods, and a significantly
greater proportion of these children had inadequate intakes of calcium and
vitamin D compared to their peers. In conclusion, the results from this study
suggest that a substantial population of American infants and children from 0 to
five years of age did not meet food group recommendations and had inadequate
intakes of key nutrients such as calcium, vitamin D, and vitamin E from foods.
PMID- 29949892
TI - Integrating Qualitative and Quantitative Data in the Development of Outcome
Measures: The Case of the Recovering Quality of Life (ReQoL) Measures in Mental
Health Populations.
AB - While it is important to treat symptoms, there is growing recognition that in
order to help people with mental health problems lead meaningful and fulfilling
lives, it is crucial to capture the impact of their conditions on wider aspects
of their social lives. We constructed two versions of the Recovering Quality of
Life (ReQoL) measure—ReQoL-10 and ReQoL-20—for use in routine
settings and clinical trials from a larger pool of items by combining qualitative
and quantitative evidence covering six domains. Qualitative evidence was gathered
through interviews and focus groups with over 76 service users, clinicians, and a
translatability assessment. Psychometric evidence generated from data from over
6200 service users was obtained from confirmatory factor models and item response
theory analyses. In this paper we present an approach based on a traffic light
pictorial format that was developed to present qualitative and quantitative
evidence to a group of service users, clinicians, and researchers to help to make
the final selection. This work provides a pragmatic yet rigorous approach to
combining qualitative and quantitative evidence to ensure that ReQoL is
psychometrically robust and has high relevance to service users and clinicians.
This approach can be extended to the development of patient reported outcome
measures in general.
PMID- 29949891
TI - Ethanol Reinforcement Elicits Novel Response Inhibition Behavior in a Rat Model
of Ethanol Dependence.
AB - Lower impulse control is a known risk factor for drug abuse vulnerability.
Chronic experience with illicit drugs is suggested to enhance impulsivity and
thereby perpetuate addiction. However, the nature of this relationship
(directionality, causality) with regard to alcohol use disorder is unclear. The
present study tested the hypothesis that higher impulsivity is observed during
chronic intermittent ethanol vapor inhalation (CIE; a model of ethanol
dependence) and subsequent abstinence from CIE in adult Wistar rats. Impulsivity
was tested using a differential reinforcement of low rates 15 s (DRL15) schedule
using either nondrug reward (palatable modified sucrose pellets) or sweetened
ethanol. A decrease in the efficiency of earning reinforcers (expressed as %
reinforcers/responses) is indicative of a decrease in response inhibition or an
increase in impulsivity. The efficiency of reinforcement and amount of
reinforcers earned were unaltered in CIE and control animals when the reinforcer
was sucrose. When the reinforcer was sweetened ethanol, the efficiency of
reinforcement increased in CIE rats compared with controls only during protracted
abstinence. Responding for sweetened ethanol under a progressive-ratio schedule
was more rapid in CIE rats during protracted abstinence. Contrary to the initial
hypothesis, impulsivity did not increase in rats with a history of CIE; instead,
it decreased when ethanol was used as the reinforcer. Furthermore, although the
efficiency of ethanol reinforcement did not differ between CIE and control
animals during CIE, CIE rats escalated the amount of sweetened ethanol consumed,
suggesting that behavioral adaptations that are induced by CIE in rats that are
tested under a DRL15 schedule appear to be targeted toward the maximization of
ethanol intake and thus may contribute to escalation and relapse.
PMID- 29949893
TI - An Exception Handling Approach for Privacy-Preserving Service Recommendation
Failure in a Cloud Environment.
AB - Service recommendation has become an effective way to quickly extract insightful
information from massive data. However, in the cloud environment, the quality of
service (QoS) data used to make recommendation decisions are often monitored by
distributed sensors and stored in different cloud platforms. In this situation,
integrating these distributed data (monitored by remote sensors) across different
platforms while guaranteeing user privacy is an important but challenging task,
for the successful service recommendation in the cloud environment. Locality
Sensitive Hashing (LSH) is a promising way to achieve the abovementioned data
integration and privacy-preservation goals, while current LSH-based
recommendation studies seldom consider the possible recommendation failures and
hence reduce the robustness of recommender systems significantly. In view of this
challenge, we develop a new LSH variant, named converse LSH, and then suggest an
exception handling approach for recommendation failures based on the converse LSH
technique. Finally, we conduct several simulated experiments based on the well
known dataset, i.e., Movielens to prove the effectiveness and efficiency of our
approach.
PMID- 29949894
TI - Dietary Patterns in Secondary Prevention of Heart Failure: A Systematic Review.
AB - BACKGROUND: Diet is an important factor in secondary prevention of heart failure
(HF) but there is still no consensus as to which dietary model should be adopted
by this population. This systematic review aims to clarify the relationship
between dietary patterns and secondary prevention in HF. METHODS: We searched the
Medline, Embase and Cochrane databases for studies with different dietary
patterns and outcomes of secondary prevention in HF. No limitation was used in
the search. RESULTS: 1119 articles were identified, 12 met the inclusion
criteria. Studies with Dietary Approaches to Stop Hypertension (DASH),
Mediterranean, Hyperproteic and Low-carb diets were found. The DASH pattern
showed improvement in cardiac function, functional capacity, blood pressure,
oxidative stress and mortality. The Mediterranean diet had a correlation with
inflammation, quality of life and cardiac function but just on cross-sectional
studies. Regarding the Hyperproteic and Low-carb diets only one study was found
with each pattern and both were able to improve functional capacity in patients
with HF. CONCLUSIONS: DASH pattern may have benefits in the secondary prevention
of HF. The Mediterranean diet demonstrated positive correlation with factors of
secondary prevention of HF but need more RCTs and cohort studies to confirm these
effects. In addition, the Hyperproteic and Low-carb diets, despite the lack of
studies, also demonstrated positive effects on the functional capacity in
patients with HF.
PMID- 29949895
TI - Willingness to Participate in a National Precision Medicine Cohort: Attitudes of
Chronic Kidney Disease Patients at a Cleveland Public Hospital.
AB - Multiple ongoing, government-funded national efforts longitudinally collect
health data and biospecimens for precision medicine research with ascertainment
strategies increasingly emphasizing underrepresented groups in biomedical
research. We surveyed chronic kidney disease patients from an academic, public
integrated tertiary care system in Cleveland, Ohio, to examine local attitudes
toward participation in large-scale government-funded studies. Responses (n =
103) indicate the majority (71%) would participate in a hypothetical national
precision medicine cohort and were willing to send biospecimens to a national
repository and share de-identified data, but <50% of respondents were willing to
install a phone app to track personal data. The majority of participants (62%)
indicated that return of research results was very important, and the majority
(54%) also wanted all of their research-collected health and genetic data
returned. Response patterns did not differ by race/ethnicity. Overall, we found
high willingness to participate among this Cleveland patient population already
participating in a local genetic study. These data suggest that despite common
perceptions, subjects from communities traditionally underrepresented in genetic
research will participate and agree to store samples and health data in
repositories. Furthermore, most participants want return of research results,
which will require a plan to provide these data in a secure, accessible, and
understandable manner.
PMID- 29949896
TI - Combined Effects of Texture and Grain Size Distribution on the Tensile Behavior
of alpha-Titanium.
AB - This work analyzes the role of both the grain size distribution and the
crystallographic texture on the tensile behavior of commercially pure titanium.
Specimens with different microstructures, especially with several mean grain
sizes, were specifically prepared for that purpose. It is observed that the yield
stress depends on the grain size following a Hall-Petch relationship, that the
stress-strain curves have a tendency to form a plateau that becomes more and more
pronounced with decreasing mean grain size and that the hardening capacity
increases with the grain size. All these observations are well reproduced by an
elasto-visco-plastic self-consistent model that incorporates grain size effects
within a crystal plasticity framework where dislocations’ densities are the
state variables. First, the critical resolved shear stresses are made dependent
on the individual grain size through the addition of a Hall-Petch type term.
Then, the main originality of the model comes from the fact that the
multiplication of mobile dislocation densities is also made grain size dependent.
The underlying assumption is that grain boundaries act mainly as barriers or
sinks for dislocations. Hence, the smaller the grain size, the smaller the
expansion of dislocation loops and thus the smaller the increase rate of mobile
dislocation density is. As a consequence of this hypothesis, both mobile and
forest dislocation densities increase with the grain size and provide an
explanation for the grain size dependence of the transient low work hardening
rate and hardening capacity.
PMID- 29949897
TI - Changes in Fish Consumption Desire and Its Factors: A Comparison between the
United Kingdom and Singapore.
AB - It is widely known that rapid population growth and income improvement in some
developing countries, and growing health consciousness in some developed
countries, are the main factors that have contributed to the global increase in
the consumption of fishery products in the past few decades. While a detailed
analysis of fish consumption behavior is being conducted in several countries,
there are other countries where changes in fish consumption desire and their
social and psychological factors are not fully clarified. This study investigates
the changes in fish consumption desire and its associated factors in the United
Kingdom (UK) and Singapore. Primary data were gathered from 1200 participants
through a web questionnaire survey in the UK and Singapore. The results show that
approximately five times as many respondents stated that the desire to purchase
fish had increased in both the UK and Singapore compared to those that believed
it had not 10 years ago. Second, the increase in fish consumption in the UK is
positively associated with younger age, cheaper price, the health benefits of
fish, concern over the health of meat, and religion. Third, the increase in fish
consumption in Singapore is positively associated with cheaper prices and is
negatively associated with concerns over sustainability.
PMID- 29949898
TI - Enhancement on the Surface Hydrophobicity and Oleophobicity of an Organosilicon
Film by Conformity Deposition and Surface Fluorination Etching.
AB - In this work, the surface morphology of a hydrophobic organosilicon film was
modified as it was deposited onto a silver seed layer with nanoparticles. The
surface hydrophobicity evaluated by the water contact angle was significantly
increased from 100° to 128° originating from the surface of the
organosilicon film becoming roughened, and was deeply relevant to the Ag seed
layer conform deposition. In addition, the organosilicon film became surface
oleophobic and the surface hydrophobicity was improved due to the formation of
the inactive C-F chemical on the surface after the carbon tetrafluoride glow
discharge etching. The surface hydrophobicity and oleophobicity of the
organosilicon film could be further optimized with water and oleic contact angles
of about 138° and 61°, respectively, after an adequate fluorination
etching.
PMID- 29949901
TI - Morphogenetic Variability and Hypertension in Ischemic Stroke Patients
Preliminary Study.
AB - In this study, we evaluated and compared the morphogenetic variability and the
degree of recessive homozygosity in patients with manifested ischemic stroke
compared to healthy controls. We have evaluated 120 patients with manifested
ischemic stroke, of which 64 did not have hypertension and 56 have hypertension.
For comparison, we additionally tested 194 healthy individuals without manifested
ischemic stroke (controls). For the estimation of the degree of recessive
homozygosity, we have performed the homozygously recessive characteristics (HRC)
test and tested 19 HRCs. There was a significant difference in the individual
variations of 19 HRCs between the controls and patients with manifested ischemic
stroke (∑χ2 = 60.162, p < 0.01). The mean values of the tested HRCs
significantly differed between the controls and group with manifested ischemic
stroke (Controls − 5.71 +/- 1.61, Ischemic stroke group − 6.25 +/-
1.54, p = 0.012). For the tested individuals with hypertension, the mean values
of HRCs did not significantly differ between the controls and those that had
manifested ischemic stroke (Controls − 5.28 +/- 1.75, Ischemic stroke group
− 5.64 +/- 1.48, p = 0.435). We found a significant difference in the
frequencies of HRCs between those with and without hypertension for controls (p <
0.003) and for those with manifested ischemic stroke (p < 0.001). There are
increased degrees of recessive homozygosity along with decreased variability in
patients with manifested ischemic stroke compared to controls.
PMID- 29949899
TI - Linoleic Acid Attenuates the Toxic Dose of Bupivacaine-Mediated Reduction of
Vasodilation Evoked by the Activation of Adenosine Triphosphate-Sensitive
Potassium Channels.
AB - The goal of this study was to investigate the effect of lipid emulsion on a toxic
dose of local anesthetic-mediated reduction of vasodilation evoked by the ATP
sensitive potassium (KATP) channel agonist levcromakalim. The effect of lipid
emulsion (LE) and linoleic acid on the local anesthetic-mediated reduction of
vasodilation and membrane hyperpolarization evoked by levcromakalim was assessed
in isolated endothelium-denuded vessels (rat aorta and mesenteric artery) and
aortic vascular smooth muscle cells. The effect of LE and linoleic acid on KATP
channel activity in transfected HEK-293 cells was investigated, as was the effect
of LE on bupivacaine concentration. The efficacy of LE in attenuating the local
anesthetic-mediated reduction of vasodilation evoked by levcromakalim was
correlated with the lipid solubility of the local anesthetic. Linoleic acid
attenuated the bupivacaine-mediated reduction of vasodilation evoked by
levcromakalim. LE decreased the bupivacaine-mediated reduction of membrane
hyperpolarization evoked by levcromakalim but did not significantly alter the
mepivacaine-mediated reduction. LE and linoleic acid both reversed the
bupivacaine-mediated decrease of KATP activity and enhanced KATP activity. LE
decreased the bupivacaine concentration. Linoleic acid may be the major
contributor to LE-induced attenuation of bupivacaine-mediated reduction of
vasodilation evoked by levcromakalim via the direct activation of KATP channels
and indirect effects.
PMID- 29949900
TI - Whole-Genome Comparison Reveals Divergent IR Borders and Mutation Hotspots in
Chloroplast Genomes of Herbaceous Bamboos (Bambusoideae: Olyreae).
AB - Herbaceous bamboos (Olyreae) are a separate lineage with idiosyncratic traits,
e.g., unisexual flowers and annual or seasonal flowering lifestyle, in the grass
family. To elucidate the evolution of herbaceous bamboos we produced two complete
chloroplast (cp) genomes from two monotypic genera i.e., Froesiochloa and Rehia
via the genome-skimming approach. The assembled F. boutelouoides and R. nervata
cp genomes were 135,905 and 136,700 base-pair (bp), respectively. Further whole
genome comparative analyses revealed that the cp genes order was perfectly
collinear, but the inverted repeats (IRs) borders, i.e., the junctions between
IRs and single copy regions, were highly divergent in Olyreae. The IRs
expansions/contractions occurred frequently in Olyreae, which have caused gene
content and genome size variations, e.g., the copy number reduction of rps19 and
trnH(GUG) genes in Froesiochloa. Subsequent nucleotide mutation analyses
uncovered a greatly heterogeneous divergence pattern among different cpDNA
regions in Olyreae cp genomes. On average, non-coding loci evolved at a rate of
circa 1.9 times faster than coding loci, from which 20 rapidly evolving loci were
determined as potential genetic markers for further studies on Olyreae. In
addition, the phylogenomic analyses from 67 grass plastomes strongly supported
the phylogenetic positions of Froesiochloa and Rehia in the Olyreae.
PMID- 29949902
TI - Effect of Social Media on Child Obesity: Application of Structural Equation
Modeling with the Taguchi Method.
AB - Through public health studies, specifically on child obesity modeling, research
scholars have been attempting to identify the factors affecting obesity using
suitable statistical techniques. In recent years, regression, structural equation
modeling (SEM) and partial least squares (PLS) regression have been the most
widely employed statistical modeling techniques in public health studies. The
main objective of this study to apply the Taguchi method to introduce a new
pattern rather than a model for analyzing the body mass index (BMI) of children
as a representative of childhood obesity levels mainly related to social media
use. The data analysis includes two main parts. The first part entails selecting
significant indicators for the proposed framework by applying SEM for primary and
high school students separately. The second part introduces the Taguchi method as
a realistic and reliable approach to exploring which combination of significant
variables leads to high obesity levels in children. AMOS software (IBM, Armonk,
NY, USA) was applied in the first part of data analysis and MINITAB software
(Minitab Inc., State College, PA, USA) was utilized for the Taguchi experimental
analysis (second data analysis part). This study will help research scholars view
the data and a pattern rather than a model, as a combination of different factor
levels for target factor optimization.
PMID- 29949903
TI - The Influence of Nanomaterials on the Thermal Resistance of Cement-Based
Composites-A Review.
AB - Exposure to elevated temperatures has detrimental effects on the properties of
cementitious composites, leading to irreversible changes, up to total failure.
Various methods have been used to suppress the deterioration of concrete under
elevated temperature conditions. Recently, nanomaterials have been introduced as
admixtures, which decrease the thermal degradation of cement-based composites
after exposure to high temperatures. This paper presents a comprehensive review
of recent developments related to the effects of nanoparticles on the thermal
resistance of cementitious composites. The review provides an updated report on
the effects of temperature on the properties of cement-based composites, as well
as a detailed analysis of the available literature regarding the inclusion of
nanomaterials and their effects on the thermal degradation of cementitious
composites. The data from the studies reviewed indicate that the inclusion of
nanoparticles in composites protects from strength loss, as well as contributing
to a decrease in disruptive cracking, after thermal exposure. From all the
nanomaterials presented, nanosilica has been studied the most extensively.
However, there are other nanomaterials, such as carbon nanotubes, graphene oxide,
nanoclays, nanoalumina or nano-iron oxides, that can be used to produce heat
resistant cementitious composites. Based on the data available, it can be
concluded that the effects of nanomaterials have not been fully explored and that
further investigations are required, so as to successfully utilize them in the
production of heat-resistant cementitious composites.
PMID- 29949904
TI - On the Determination of Uncertainty and Limit of Detection in Label-Free
Biosensors.
AB - A significant amount of noteworthy articles reviewing different label-free
biosensors are being published in the last years. Most of the times, the
comparison among the different biosensors is limited by the procedure used of
calculating the limit of detection and the measurement uncertainty. This article
clarifies and establishes a simple procedure to determine the calibration
function and the uncertainty of the concentration measured at any point of the
measuring interval of a generic label-free biosensor. The value of the limit of
detection arises naturally from this model as the limit at which uncertainty
tends when the concentration tends to zero. The need to provide additional
information, such as the measurement interval and its linearity, among others, on
the analytical systems and biosensor in addition to the detection limit is
pointed out. Finally, the model is applied to curves that are typically obtained
in immunoassays and a discussion is made on the application validity of the model
and its limitations.
PMID- 29949905
TI - A Strap-Down Inertial Navigation/Spectrum Red-Shift/Star Sensor (SINS/SRS/SS)
Autonomous Integrated System for Spacecraft Navigation.
AB - This paper presents a new Strap-down Inertial Navigation System/Spectrum Red
Shift/Star Sensor (SINS/SRS/SS) system integration methodology to improve the
autonomy and reliability of spacecraft navigation using the spectrum red-shift
information from natural celestial bodies such as the Sun, Jupiter and the Earth.
The system models for SINS/SRS/SS integration are established. The information
fusion of SINS/SRS/SS integration is designed as the structure of the federated
Kalman filter to fuse the local estimations of SINS/SRS and SINS/SS integrated
subsystems to generate the global state estimation for spacecraft navigation. A
new robust adaptive unscented particle filter is also developed to obtain the
local state estimations of SINS/SRS and SINS/SS integrated subsystems in a
parallel manner. The simulation results demonstrate that the proposed methodology
for SINS/SRS/SS integration can effectively calculate navigation solutions,
leading to strong autonomy and high reliability for spacecraft navigation.
PMID- 29949907
TI - The Bacteriophage T4 MotB Protein, a DNA-Binding Protein, Improves Phage Fitness.
AB - The lytic bacteriophage T4 employs multiple phage-encoded early proteins to
takeover the Escherichia coli host. However, the functions of many of these
proteins are not known. In this study, we have characterized the T4 early gene
motB, located in a dispensable region of the T4 genome. We show that heterologous
production of MotB is highly toxic to E. coli, resulting in cell death or growth
arrest depending on the strain and that the presence of motB increases T4 burst
size 2-fold. Previous work suggested that motB affects middle gene expression,
but our transcriptome analyses of T4 motBam vs. T4 wt infections reveal that only
a few late genes are mildly impaired at 5 min post-infection, and expression of
early and middle genes is unaffected. We find that MotB is a DNA-binding protein
that binds both unmodified host and T4 modified [(glucosylated, hydroxymethylated
5 cytosine, (GHme-C)] DNA with no detectable sequence specificity. Interestingly,
MotB copurifies with the host histone-like proteins, H-NS and StpA, either
directly or through cobinding to DNA. We show that H-NS also binds modified T4
DNA and speculate that MotB may alter how H-NS interacts with T4 DNA, host DNA,
or both, thereby improving the growth of the phage.
PMID- 29949906
TI - Crystal Structure of LSD1 in Complex with 4-[5-(Piperidin-4-ylmethoxy)-2-(p
tolyl)pyridin-3-yl]benzonitrile.
AB - Because lysine-specific demethylase 1 (LSD1) regulates the maintenance of cancer
stem cell properties, small-molecule inhibitors of LSD1 are expected to be useful
for the treatment of several cancers. Reversible inhibitors of LSD1 with
submicromolar inhibitory potency have recently been reported, but their exact
binding modes are poorly understood. In this study, we synthesized a recently
reported reversible inhibitor, 4-[5-(piperidin-4-ylmethoxy)-2-(p-tolyl)pyridin-3
yl]benzonitrile, which bears a 4-piperidinylmethoxy group, a 4-methylphenyl
group, and a 4-cyanophenyl group on a pyridine ring, and determined the crystal
structure of LSD1 in complex with this inhibitor at 2.96 Å. We observed
strong electron density for the compound, showing that its cyano group forms a
hydrogen bond with Lys661, which is a critical residue in the lysine
demethylation reaction located deep in the catalytic center of LSD1. The
piperidine ring interacts with the side chains of Asp555 and Asn540 in two
conformations, and the 4-methylphenyl group is bound in a hydrophobic pocket in
the catalytic center. Our elucidation of the binding mode of this compound can be
expected to facilitate the rational design of more-potent reversible LSD1
inhibitors.
PMID- 29949908
TI - Cutting-Processed Single-Wall Carbon Nanotubes with Additional Edge Sites for
Supercapacitor Electrodes.
AB - Carbon nanotubes are frequently selected for supercapacitors because of their
major intrinsic properties of mechanical and chemical stability, in addition to
their excellent electrical conductivity. However, electrodes using carbon
nanotubes suffer from severe performance degradation by the phenomenon of re
stacking during fabrication, which hinders ion accessibility. In this study,
short single-wall carbon nanotubes were further shortened by sonication-induced
cutting to increase the proportion of edge sites. This longitudinally short
structure preferentially exposes the active edge sites, leading to high
capacitance during operation. Supercapacitors assembled using the shorter-cut
nanotubes exhibit a 7-fold higher capacitance than those with pristine single
wall nanotubes while preserving other intrinsic properties of carbon nanotubes,
including excellent cycle performance and rate capability. The unique structure
suggests a design approach for achieving a high specific capacitance with those
low-dimensional carbon materials that suffer from re-stacking during device
fabrication.
PMID- 29949909
TI - Mahimbrine A, a Novel Isoquinoline Alkaloid Bearing a Benzotropolone Moiety from
Mahonia imbricata.
AB - A novel isoquinoline alkaloid, mahimbrine A, possessing a rare benzotropolone
framing scaffold, was isolated from the endemic plant of Mahonia imbricata. Its
structure was established on the basis of extensive spectroscopic analysis. A
plausible biosynthetic route of mahimbrine A was proposed. Mahimbrine A showed no
antimicrobial activity at the concentration of 1 mg/mL.
PMID- 29949912
TI - Rub-Impact Fault Diagnosis Using an Effective IMF Selection Technique in Ensemble
Empirical Mode Decomposition and Hybrid Feature Models.
AB - The complex nature of rubbing faults makes it difficult to use traditional signal
analysis methods for feature extraction. Various time-frequency analysis
approaches based on signal decomposition, such as empirical mode decomposition
(EMD) and ensemble EMD (EEMD), have been widely utilized recently to analyze rub
impact faults. However, traditional EMD suffers from “mode-mixing”,
and in both EMD and EEMD the relevance of the extracted components to rubbing
processes must be determined. In this paper, we introduce a new informative
intrinsic mode function (IMF) selection method for EEMD and a hybrid feature
model for diagnosing rub-impact faults of various intensities. Our method uses a
novel selection procedure that combines the degree-of-presence ratio of rub
impact and a Kullback-Leibler divergence-based similarity measure into an IMF
quality metric with adaptive threshold-based selection to pick the meaningful
signal-dominant modes. Signals reconstructed using the selected IMFs contained
explicit information about the rubbing faults and are used for hybrid feature
extraction. Experimental results demonstrated that the proposed approach
effectively defines meaningful IMFs for rubbing processes, and the presented
hybrid feature model allows for the classification of rub-impact faults of
various intensities with good accuracy.
PMID- 29949911
TI - Application of Biosensors Based on Lipid Membranes for the Rapid Detection of
Toxins.
AB - Lipid assemblies in the form of two dimensional films have been used extensively
as biosensing platforms. These films exhibit certain similarities with cell
membranes, thus providing a suitable means for the immobilization of
proteinaceous moieties and, further, a number of intrinsic signal amplification
mechanisms. Their implementation in the detection of toxins yielded reliable and
fast detectors for in field analyses of environmental and clinical samples. Some
examples are presented herein, including aflatoxin and cholera toxin detection.
The conditions and parameters that determine the analytical specifications of the
lipid membrane sensors are discussed, advantages and technology bottlenecks are
reviewed, and possible further developments are highlighted.
PMID- 29949910
TI - Synthesis and Comparative Evaluation of Novel Cationic Amphiphile C12-Man-Q as an
Efficient DNA Delivery Agent In Vitro.
AB - New amphiphilic 1,4-DHP derivative C12-Man-Q with remoted cationic moieties at
positions 2 and 6 was synthesised to study DNA delivery activity. The results
were compared with data obtained for cationic 1,4-DHP derivative D19, which is
known to be the most efficient one among the previously tested 1,4-DHP
amphiphiles. We analysed the effects of C12-Man-Q concentration, complexation
media, and complex/cell contact time on the gene delivery effectiveness and cell
viability. Transmission electron microscopy data confirms that lipoplexes formed
by the compound C12-Man-Q were quite uniform, vesicular-like structures with
sizes of about 50 nm, and lipoplexes produced by compound D19 were of irregular
shapes, varied in size in the range of 25-80 nm. Additionally, confocal
microscopy results revealed that both amphiphiles effectively delivered green
fluorescent protein expression plasmid into BHK-21 cells and produced a
fluorescent signal with satisfactory efficiency, although compound C12-Man-Q was
more cytotoxic to the BHK-21 cells with an increase of concentration. It can be
concluded that optimal conditions for C12-Man-Q lipoplexes delivery in BHK-21
cells were the serum free media without 0.15 M NaCl, at an N/P ratio of 0.9.
Compound D19 showed higher transfection efficiency to transfect BHK-21 and Cos-7
cell lines, when transfecting active proliferating cells. Although D19 was not
able to transfect all studied cell lines we propose that it could be cell type
specific. The compound C12-Man-Q showed modest delivery activity in all used cell
lines, and higher activity was obtained in the case of H2-35 and B16 cells. The
transfection efficiency in cell lines MCF-7, HeLa, and Huh-7 appears to be
comparable to the reference compound D19 and minimal in the HepG2 cell line.
PMID- 29949913
TI - Effect of Skeletal Muscle and Fat Mass on Muscle Strength in the Elderly.
AB - It is important for elderly people to maintain or improve muscle strength and for
clinicians to know the factors that affect muscle strength. Therefore, the
purpose of this study was to compare the effects of fat mass (FM) and skeletal
muscle mass (SMM) on muscle strength. The participants included 192 community
dwelling elderly women. The SMM and FM, grip strength, and knee extension
strength were measured. Data were evaluated using stepwise multiple linear
regression analysis, which was performed with grip or knee extension strength as
a dependent variable and the SMM and FM of the upper and lower limbs as the
independent variables. The SMM and FM of the upper limbs were associated with
grip strength, whereas the SMM but not the FM of the lower limbs was associated
with knee extension strength. These findings suggest that there may be thresholds
for the SMM/FM ratio to affect muscle strength.
PMID- 29949915
TI - The Desmosomal Cadherin Desmoglein-2 Experiences Mechanical Tension as
Demonstrated by a FRET-Based Tension Biosensor Expressed in Living Cells.
AB - Cell-cell junctions are critical structures in a number of tissues for
mechanically coupling cells together, cell-to-cell signaling, and establishing a
barrier. In many tissues, desmosomes are an important component of cell-cell
junctions. Loss or impairment of desmosomes presents with clinical phenotypes in
the heart and skin as cardiac arrhythmias and skin blistering, respectively.
Because heart and skin are tissues that are subject to large mechanical stresses,
we hypothesized that desmosomes, similar to adherens junctions, would also
experience significant tensile loading. To directly measure mechanical forces
across desmosomes, we developed and validated a desmoglein-2 (DSG-2) force
sensor, using the existing TSmod Förster resonance energy transfer (FRET)
force biosensor. When expressed in human cardiomyocytes, the force sensor
reported high tensile loading of DSG-2 during contraction. Additionally, when
expressed in Madin-Darby canine kidney (MDCK) epithelial or epidermal (A431)
monolayers, the sensor also reported tensile loading. Finally, we observed higher
DSG-2 forces in 3D MDCK acini when compared to 2D monolayers. Taken together, our
results show that desmosomes experience low levels of mechanical tension in
resting cells, with significantly higher forces during active loading.
PMID- 29949916
TI - Visual Information Fusion through Bayesian Inference for Adaptive Probability
Oriented Feature Matching.
AB - This work presents a visual information fusion approach for robust probability
oriented feature matching. It is sustained by omnidirectional imaging, and it is
tested in a visual localization framework, in mobile robotics. General visual
localization methods have been extensively studied and optimized in terms of
performance. However, one of the main threats that jeopardizes the final
estimation is the presence of outliers. In this paper, we present several
contributions to deal with that issue. First, 3D information data, associated
with SURF (Speeded-Up Robust Feature) points detected on the images, is inferred
under the Bayesian framework established by Gaussian processes (GPs). Such
information represents a probability distribution for the feature points’
existence, which is successively fused and updated throughout the robot’s
poses. Secondly, this distribution can be properly sampled and projected onto the
next 2D image frame in t+1, by means of a filter-motion prediction. This strategy
permits obtaining relevant areas in the image reference system, from which
probable matches could be detected, in terms of the accumulated probability of
feature existence. This approach entails an adaptive probability-oriented
matching search, which accounts for significant areas of the image, but it also
considers unseen parts of the scene, thanks to an internal modulation of the
probability distribution domain, computed in terms of the current uncertainty of
the system. The main outcomes confirm a robust feature matching, which permits
producing consistent localization estimates, aided by the odometer’s prior
to estimate the scale factor. Publicly available datasets have been used to
validate the design and operation of the approach. Moreover, the proposal has
been compared, firstly with a standard feature matching and secondly with a
localization method, based on an inverse depth parametrization. The results
confirm the validity of the approach in terms of feature matching, localization
accuracy, and time consumption.
PMID- 29949914
TI - Phytochemical Composition of the Decoctions of Greek Edible Greens (Chorta) and
Evaluation of Antioxidant and Cytotoxic Properties.
AB - Wild or semi-wild edible greens (chórta) are an integral part of the
traditional Greek Mediterranean diet due to their nutritional value, containing
various phytonutrients beneficial to human health. Water-based decoctions of
chórta are widely consumed in Greek alternative medicine as health
promoting agents. This study examined the chemical profile of the decoctions of
eight edible plants, Cichorium intybus, C. endivia, C. spinosum, Crepis sancta,
Sonchus asper, Carthamus lanatus, Centaurea raphanina, and Amaranthus blitum, by
UPLC-ESI-HRMS and HRMS/MS analysis, to determine possibly bioactive constituents.
The profiles of the plants from the Asteraceae family are dominated by the
presence of phenolic acids and flavonoid derivatives, whereas the A. blitum
decoction is rich in triterpene saponins. Interestingly, the Centaurea raphanina
decoction was found to be extremely rich in flavanones, particularly in the
aglycone pinocembrin. Further phytochemical investigation and fractionation of
this extract resulted in the isolation and identification of five compounds:
phlorin (1), syringin (2), pinocembrin (3), pinocembroside (4), and pinocembrin-7
O-neohesperidoside (5). The extracts were also tested for their antioxidant and
differential cytotoxic activity against tumor cells. C. raphanina was found to be
differentially toxic against metastatic tumor cells. In conclusion, we found that
Greek edible greens are a rich source of bioactive secondary metabolites and
their consumption could contribute to the maintenance of overall health.
PMID- 29949917
TI - The RNA Helicase DDX6 Associates with RIG-I to Augment Induction of Antiviral
Signaling.
AB - Virus infections induce sensitive antiviral responses within the host cell. The
RNA helicase retinoic acid-inducible gene I (RIG-I) is a key sensor of influenza
virus RNA that induces the expression of antiviral type I interferons. Recent
evidence suggests a complex pattern of RIG-I regulation involving multiple
interactions and cellular sites. In an approach employing affinity purification
and quantitative mass spectrometry, we identified proteins with increased binding
to RIG-I in response to influenza B virus infection. Among them was the RIG-I
related RNA helicase DEAD box helicase 6 (DDX6), a known component of cytoplasmic
mRNA-ribonucleoprotein (mRNP) granules like P-bodies and stress granules (SGs).
RIG-I and DDX6 both localized to the cytosol and were detected in virus-induced
SGs. Coimmunoprecipitation assays detected a basal level of complexes harboring
RIG-I and DDX6 that increased after infection. Functionally, DDX6 augmented RIG-I
mediated induction of interferon (IFN)-β expression. Notably, DDX6 was found
to bind viral RNA capable to stimulate RIG-I. These findings imply a novel
function for DDX6 as an RNA co-sensor and signaling enhancer for RIG-I.
PMID- 29949918
TI - Metabolomic Changes in Sogatella furcifera under Southern rice black-streaked
dwarf virus Infection and Temperature Stress.
AB - Southern rice black-streaked dwarf virus (SRBSDV) is a devastating newly emerged
rice reovirus in Eastern and Southeastern Asia transmitted by a long-distance
migratory pest, the white-backed planthopper (WBPH). We previously showed that
SRBSDV infection decreased the cold tolerance but improved the heat tolerance of
its vector, WBPH. Comparative metabolomic analysis was used to explore the
potential mechanisms underlying these changes in temperature stress response.
Fourth-generation WBPH nymphs were treated with SRBSDV and/or extreme temperature
stress and were analyzed using gas chromatography-time of flight-mass
spectrometry. A total of 605 distinguishable peaks were identified and 165, 207,
and 202 differentially accumulated metabolites were identified in WBPH after
virus infection, cold, or heat stress, respectively. The nucleic acids and fatty
acids were the major categories of metabolites regulated by SRBSDV infection,
whereas temperature stress regulated tricarboxylic acid cycle compounds, sugars,
and polyols. For the WBPH samples infected with SRBSDV and subjected to
temperature stress, amino acids, sugars, and polyols were the most significant
regulated metabolites. The metabolomics study suggests that SRBSDV may influence
the extreme temperature tolerance of WBPH by regulating the accumulation of amino
acids, sugars, and polyols in the insect body.
PMID- 29949920
TI - Effect of Lipid Additives and Drug on the Rheological Properties of Molten
Paraffin Wax, Degree of Surface Drug Coating, and Drug Release in Spray-Congealed
Microparticles.
AB - Paraffin wax is potentially useful for producing spray-congealed drug-loaded
microparticles with sustained-release and taste-masking properties. To date,
there is little information about the effects of blending lipids with paraffin
wax on the melt viscosity. In addition, drug particles may not be entirely coated
by the paraffin wax matrix. In this study, drug-loaded paraffin wax
microparticles were produced by spray-congealing, and the effects of lipid
additives on the microparticle production were investigated. The influence of
lipid additives (stearic acid, cetyl alcohol, or cetyl esters) and drug
(paracetamol) on the rheological properties of paraffin wax were elucidated.
Fourier transform-infrared spectroscopy was conducted to investigate the
interactions between the blend constituents. Selected formulations were spray
congealed, and the microparticles produced were characterized for their size,
drug content, degree of surface drug coating, and drug release. The viscosity of
wax-lipid blends was found to be mostly lower than the weighted viscosity when
interactions occurred between the blend constituents. Molten paraffin wax
exhibited Newtonian flow, which was transformed to plastic flow by paracetamol
and pseudoplastic flow by the lipid additive. The viscosity was decreased with
lipid added. Compared to plain wax, wax-lipid blends produced smaller spray
congealed microparticles. Drug content remained high. Degree of surface drug
coating and drug release were also higher. The lipid additives altered the
rheological properties and hydrophobicity of the melt and are useful for
modifying the microparticle properties.
PMID- 29949921
TI - Coumarin Probe for Selective Detection of Fluoride Ions in Aqueous Solution and
Its Bioimaging in Live Cells.
AB - We have synthesized novel coumarin-based fluorescent chemosensors for detection
of fluoride ions in aqueous solution. The detection mechanism relied on a
fluoride-mediated desilylation triggering fluorogenic reaction and a strong
interaction between fluoride and the silicon center. In this work, the hydroxyl
decorated coumarins containing oxysilyl moiety have been synthesized through the
aldehyde-functionalized coumarins. The optical responses toward fluoride, as well
as aqueous stability studies of both aldehyde and hydroxyl functionalized
coumarins, have been investigated. Due to the highest fluorescence enhancement
upon the addition of fluoride and good stability in aqueous solution, the
hydroxyl-decorated coumarin connected with the bulky tert-butyldiphenyloxysilyl
group (-OSitBuPh2) has been selected for further investigation of its potential
as a fluoride sensor. This hydroxyl-decorated coumarin can selectively sense
fluoride ions in aqueous media (contain 0.8% MeCN) with desirable response times
(40 min). The limit of detection of this compound was determined as 0.043 ppm,
satisfying the standard fluoride level (0.7 ppm) in drinking water recommended by
U.S. Department of Health and Human Services. The application of this silyl
capped coumarin derivative for fluoride analysis in collected water samples
displayed satisfactory analytical accuracy (<5% error). Finally, this compound
was successfully employed in fluorescence bioimaging of fluoride ions in human
liver cancer cells, indicating its excellent cell permeability, ability to retain
inside the living cells, and good stability under physiological conditions.
PMID- 29949919
TI - Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update.
AB - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood malignancy
that arises from the clonal expansion of transformed T-cell precursors. Although
T-ALL prognosis has significantly improved due to the development of intensive
chemotherapeutic protocols, primary drug-resistant and relapsed patients still
display a dismal outcome. In addition, lifelong irreversible late effects from
conventional therapy are a growing problem for leukemia survivors. Therefore,
novel targeted therapies are required to improve the prognosis of high-risk
patients. The mechanistic target of rapamycin (mTOR) is the kinase subunit of two
structurally and functionally distinct multiprotein complexes, which are referred
to as mTOR complex 1 (mTORC1) and mTORC2. These two complexes regulate a variety
of physiological cellular processes including protein, lipid, and nucleotide
synthesis, as well as autophagy in response to external cues. However, mTOR
activity is frequently deregulated in cancer, where it plays a key oncogenetic
role driving tumor cell proliferation, survival, metabolic transformation, and
metastatic potential. Promising preclinical studies using mTOR inhibitors have
demonstrated efficacy in many human cancer types, including T-ALL. Here, we
highlight our current knowledge of mTOR signaling and inhibitors in T-ALL, with
an emphasis on emerging evidence of the superior efficacy of combinations
consisting of mTOR inhibitors and either traditional or targeted therapeutics.
PMID- 29949922
TI - Rapid Evolution of Sperm Produces Diverse Centriole Structures that Reveal the
Most Rudimentary Structure Needed for Function.
AB - Centrioles are ancient subcellular protein-based organelles that maintain a
conserved number and structure across many groups of eukaryotes. Centriole number
(two per cells) is tightly regulated; each pre-existing centriole nucleates only
one centriole as the cell prepares for division. The structure of centrioles is
barrel-shaped, with a nine-fold symmetry of microtubules. This organization of
microtubules is essential for the ancestral function of centriole-cilium
nucleation. In animal cells, centrioles have gained an additional role:
recruiting pericentriolar material (PCM) to form a centrosome. Therefore, it is
striking that in animal spermatozoa, the centrioles have a remarkable diversity
of structures, where some are so anomalous that they are referred to as atypical
centrioles and are barely recognizable. The atypical centriole maintains the
ability to form a centrosome and nucleate a new centriole, and therefore reveals
the most rudimentary structure that is needed for centriole function. However,
the atypical centriole appears to be incapable of forming a cilium. Here, we
propose that the diversity in sperm centriole structure is due to rapid evolution
in the shape of the spermatozoa head and neck. The enhanced diversity may be
driven by a combination of direct selection for novel centriole functions and
pleiotropy, which eliminates centriole properties that are dispensable in the
spermatozoa function.
PMID- 29949923
TI - Ethanolic Extracts from Azadirachta indica Leaves Modulate Transcriptional Levels
of Hormone Receptor Variant in Breast Cancer Cell Lines.
AB - Breast Cancer (BC) encompasses numerous entities with different biological and
behavioral characteristics, favored by tumor molecular complexity. Azadirachta
indica (neem) presents phenolic compounds, indicating its potential as an
antineoplastic compound. The present study aimed to evaluate the cellular
response of MCF10, MCF7, and MDA-MB-231 breast cell lines to ethanolic extracts
of neem leaves (EENL) obtained by dichloromethane (DCM) and ethyl acetate (EA)
solvent. Extracts’ antiproliferative activities were evaluated against MCF
10A, MCF7, and MDA-MB-231 for 24 and 48 h using MTT assay. ESR1, ESR2, AR, AR-V1,
AR-V4, and AR-V7 transcripts were quantified through qPCR for 0.03125 μg/mL of
DCM and 1.0 μg/mL for EA for 48 h. The EENL was tested on Drosophila
melanogaster as a sole treatment and then also together with doxorubicin.
Antiproliferative effect on tumor cell lines without affecting MCF 10A were 1.0
µg/mL (P < 0.001) for EA, and 0.03125 µg/mL (P < 0.0001) for DCM,
both after 48 h. Transcriptional levels of AR-V7 increased after treatment. In
vivo assays demonstrated that EENL induced fewer tumors at a higher concentration
with doxorubicin (DXR). The behavior of AR-V7 in the MDA-MB-231 tumor lineage
indicates new pathways involved in tumor biology and this may have therapeutic
value for cancer.
PMID- 29949924
TI - Antioxidant Properties of Polyphenolic Extracts from Quercus Laurina, Quercus
Crassifolia, and Quercus Scytophylla Bark.
AB - The objective of this work was to determine the concentration of total phenols,
total flavonoids, hydroxycinnamic acids, and proanthocyanidins present in crude
extracts of Quercus laurina, Q. crassifolia, and Q. scytophylla bark. They were
extracted by ethanol (90%) maceration and hot water. The antioxidant capacity was
determined by the ability to capture OH•, O2•−, ROO•, H2O2,
NO•, and HClO. The hot water crude extract of Q. crassifolia was chosen to
be concentrated and purified due to its higher extraction yield (20.04%),
concentration of phenol compounds (747 mg gallic acid equivalent (GAE)/g, 25.4 mg
quercetin equivalent (QE)/g, 235 mg ChAE/g, 25.7 mg chlorogenic acid equivalents
(ChAE)/g), and antioxidant capacity (expressed as half maximal effective
concentration (EC50, µg/mL): OH• = 918, O2•− = 80.5,
ROO• = 577, H2O2 = 597, NO• ≥ 4000, HClO = 740). In a second stage,
Q. crassifolia extracted with hot water was treated with ethyl acetate,
concentrating the phenol compounds (860 mg GAE/g, 43.6 mg QE/g, 362 ChAE/g, 9.4
cyanidin chloride equivalents (CChE)/g) and improving the scavenging capacity
(OH• = 467, O2•− = 58.1, ROO• = 716, H2O2 = 22.0, NO•
≥ 4000, HClO = 108). Q. crassifolia had the highest polyphenolic concentration
and the better capacity for scavenging reactive species, being a favorable
candidate to be considered in the development of new products.
PMID- 29949927
TI - Multiple Access Control for Cognitive Radio-Based IEEE 802.11ah Networks.
AB - The proliferation of Internet-of-Things (IoT) technology and its reliance on the
license-free Industrial, Scientific, and Medical (ISM) bands have rendered radio
spectrum scarce. The IoT can nevertheless obtain great advantage from Cognitive
Radio (CR) technology for efficient use of a spectrum, to be implemented in IEEE
802.11af-based primary networks. However, such networks require a geolocation
database and a centralized architecture to communicate white space information on
channels. On the other hand, in spectrum sensing, CR presents various challenges
such as the Hidden Primary Terminal (HPT) problem. To this end, we focus on the
most recently released standard, i.e., IEEE 802.11ah, in which IoT stations can
first be classified into multiple groups to reduce collisions and then they can
periodically access the channel. Therein, both services are similarly supported
by a centralized server that requires signaling overhead to control the groups of
stations. In addition, more regroupings are required over time due to the
frequent variations in the number of participating stations, which leads to more
overhead. In this paper, we propose a new Multiple Access Control (MAC) protocol
for CR-based IEEE 802.11ah systems, called Restricted Access with Collision and
Interference Resolution (RACIR). We introduce a decentralized group split
algorithm that distributes the participating stations into multiple groups based
on a probabilistic estimation in order to resolve collisions. Furthermore, we
propose a decentralized channel access procedure that avoids the HPT problem and
resolves interference with the incumbent receiver. We analyze the performance of
our proposed MAC protocol in terms of normalized throughput, packet delay and
energy consumption with the Markov model and analytic expressions. The results
are quite promising, which makes the RACIR protocol a strong candidate for the CR
based IoT environment.
PMID- 29949926
TI - Supporting Parent Caregivers of Children with Life-Limiting Illness.
AB - The well-being of parents is essential to the well-being of children with life
limiting illness. Parents are vulnerable to a range of negative financial,
physical, and psychosocial issues due to caregiving tasks and other stressors
related to the illness of their child. Pediatric palliative care practitioners
provide good care to children by supporting their parents in decision-making and
difficult conversations, by managing pain and other symptoms in the ill child,
and by addressing parent and family needs for care coordination, respite,
bereavement, and social and emotional support. No matter the design or setting of
a pediatric palliative care team, practitioners can seek to provide for parent
needs by referral or intervention by the care team.
PMID- 29949928
TI - Vibration of a Rotating Micro-Ring under Electrical Field Based on Inextensible
Approximation.
AB - The problem of vibrations of rotating rings has been of interest for its wide
applications in engineering, such as the vibratory ring gyroscopes. For the
vibratory ring gyroscopes, the vibration of a micro ring is usually actuated and
sensed by means of electrostatics. The analytical models of electrostatic
microstructures are complicated due to their non-linear electromechanical
coupling behavior. Therefore, this paper presents for the first time the free
vibration of a rotating ring under uniform electrical field and the results will
be helpful for extending our knowledge on the problem of vibrations of rotating
rings, helping the design of vibratory ring gyroscopes, and inspiring the
feasibilities of other engineering applications. An analytical model, based on
thin-ring theory, is derived by means of energy method for a rotating ring under
uniformly distributed electrical field. After that, the closed form solutions of
the natural frequencies and modes are obtained by means of modal expansion
method. Some valuable conclusions are made according to the results of the
present analytical model. The electrical field causes not only an electrostatic
force but also an equivalently negative electrical-stiffness. The equivalent
negative electrical-stiffness will reduce either the natural frequencies or
critical speeds of the rotating ring. It is known that the ring will buckle when
its rotational speed equals its natural frequencies. The introduction of
electrical field will further reduce the buckling speeds to a value less than the
natural frequencies. The rotation effect will induce the so-called traveling
modes, each one travels either in the same direction as the rotating ring or in
the opposite direction with respect to stationary coordinate system. The
electrical field will reduce the traveling velocities of the traveling modes.
PMID- 29949925
TI - Physiological Hypoxia (Physioxia) Impairs the Early Adhesion of Single Lymphoma
Cell to Marrow Stromal Cell and Extracellular Matrix. Optical Tweezers Study.
AB - Adhesion is critical for the maintenance of cellular structures as well as
intercellular communication, and its dysfunction occurs prevalently during cancer
progression. Recently, a growing number of studies indicated the ability of
oxygen to regulate adhesion molecules expression, however, the influence of
physiological hypoxia (physioxia) on cell adhesion remains elusive. Thus, here we
aimed: (i) to develop an optical tweezers based assay to precisely evaluate
single diffuse large B-cell lymphoma (DLBCL) cell adhesion to neighbor cells
(mesenchymal stromal cells) and extracellular matrix (Matrigel) under normoxia
and physioxia; and, (ii) to explore the role of integrins in adhesion of single
lymphoma cell. We identified the pronouncedly reduced adhesive properties of
lymphoma cell lines and primary lymphocytes B under physioxia to both stromal
cells and Matrigel. Corresponding effects were shown in bulk adhesion assays.
Then we emphasized that impaired β1, β2 integrins, and cadherin-2
expression, studied by confocal microscopy, account for reduction in lymphocyte
adhesion in physioxia. Additionally, the blockade studies conducted with anti
integrin antibodies have revealed the critical role of integrins in lymphoma
adhesion. To summarize, the presented approach allows for precise confirmation of
the changes in single cell adhesion properties provoked by physiological hypoxia.
Thus, our findings reveal an unprecedented role of using physiologically relevant
oxygen conditioning and single cell adhesion approaches when investigating tumor
adhesion in vitro.
PMID- 29949929
TI - Experimental Model of Human Malignant Mesothelioma in Athymic Mice.
AB - Malignant pleural mesothelioma (MPM) is a thoracic aggressive cancer caused by
asbestos exposure, which is difficult to diagnose and treat. Here, we
characterized an in vivo orthotopic xenograft model consisting of human
mesothelioma cells (designed as H2052/484) derived from a pleural NCI-H2052 tumor
injected in partially immunodeficient athymic mice. We assessed tumor formation
and tumor-dependent patterns of inflammation. H2052/484 cells conserved their
mesothelioma phenotype and most characteristics from the parental NCI-H2052
cells. After intra-thoracic injection of H2052/484 cells, thoracic tumors
developed in nearly all mice (86%) within 14 days, faster than from parental NCI
H2052 cells. When the mice were euthanized, the pleural lavage fluid was examined
for immune cell profiles. The pleural immune cell population increased with tumor
development. Interestingly, the proportion of myeloid-derived suppressor cell and
macrophage (especially CD206+ M2 macrophages) populations increased in the
pleural fluid of mice with large mesothelioma development, as previously observed
in immunocompetent mice. This reliable orthotopic model recapitulates human
mesothelioma and may be used for the study of new treatment strategies.
PMID- 29949930
TI - Smart Wound Dressings for Diabetic Chronic Wounds.
AB - Given their severity and non-healing nature, diabetic chronic wounds are a
significant concern to the 30.3 million Americans diagnosed with diabetes
mellitus (2015). Peripheral arterial diseases, neuropathy, and infection
contribute to the development of these wounds, which lead to an increased
incidence of lower extremity amputations. Early recognition, debridement,
offloading, and controlling infection are imperative for timely treatment.
However, wound characterization and treatment are highly subjective and based
largely on the experience of the treating clinician. Many wound dressings have
been designed to address particular clinical presentations, but a prescriptive
method is lacking for identifying the particular state of chronic, non-healing
wounds. The authors suggest that recent developments in wound dressings and
biosensing may allow for the quantitative, real-time representation of the wound
environment, including exudate levels, pathogen concentrations, and tissue
regeneration. Development of such sensing capability could enable more strategic,
personalized care at the onset of ulceration and limit the infection leading to
amputation. This review presents an overview of the pathophysiology of diabetic
chronic wounds, a brief summary of biomaterial wound dressing treatment options,
and biosensor development for biomarker sensing in the wound environment.
PMID- 29949931
TI - Design, Synthesis and Biological Evaluation of 6,7-Disubstituted-4
phenoxyquinoline Derivatives Bearing Pyridazinone Moiety as c-Met Inhibitors.
AB - Deregulation of the receptor tyrosine kinase mesenchymal epithelial transition
factor (MET) has been implicated in several human cancers and is an attractive
target for small molecule drug discovery. Herein, a series of 6,7-disubstituted-4
phenoxyquinoline derivatives bearing pyridazinone derivatives were designed,
synthesized and evaluated for their enzymatic inhibitory activity against c-Met
kinase and cellular potency against A549, HepG2, and MCF-7 cell lines. Eight of
them are equal to more active than positive control Foretinib against one or more
cell lines and enzyme. The most promising compound 53 showed superior activity to
Foretinib, which possessed excellent c-Met kinase inhibition on a singledigital
nanomolar level (IC50 = 0.6 nM), and cancer cells of A549 (IC50 = 0.003
µM), HepG2 (IC50 = 0.49 µM) and MCF-7 cells (IC50 = 0.006 µM).
The result of AO single staining indicated that compound 53 could induce
remarkable apoptosis of HepG2 cell.
PMID- 29949932
TI - Hepatic Metabolism of Sakuranetin and Its Modulating Effects on Cytochrome P450s
and UDP-Glucuronosyltransferases.
AB - Sakuranetin (SKN), found in cherry trees and rice, is a flavanone with various
pharmacological activities. It is biosynthesized from naringenin in rice or
cherry trees, and the metabolism of SKN has been studied in non-human species.
The present study aimed to investigate the metabolic pathways of SKN in human
liver microsomes and identify the phase I and phase II metabolites, as well as
evaluate the potential for drug-herb interactions through the modulation of drug
metabolizing enzymes (DMEs). HPLC-DAD and HPLC-electrospray mass spectrometry
were used to study the metabolic stability and identify the metabolites from
human liver microsomes incubated with SKN. The potential of SKN to inhibit the
DMEs was evaluated by monitoring the formation of a DME-specific product. The
cytochrome P450 2B6 and 3A4-inductive effects were studied using promoter
reporter assays in human hepatocarcinoma cells. The major pathways for SKN
metabolism include B-ring hydroxylation, 5-O-demethylation, and conjugation with
glutathione or glucuronic acid. The phase I metabolites were identified as
naringenin and eriodictyol. SKN was found to be a UDP-glucuronosyltransferases
(UGT) 1A9 inhibitor, whereas it induced transactivation of the human pregnane X
receptor-mediated cytochrome P450 (CYP) 3A4 gene.
PMID- 29949933
TI - Role of Mn2+ Doping in the Preparation of Core-Shell Structured
Fe3O4@upconversion Nanoparticles and Their Applications in T1/T2-Weighted
Magnetic Resonance Imaging, Upconversion Luminescent Imaging and Near-Infrared
Activated Photodynamic Therapy.
AB - Core-shell (C/S) structured upconversion coated Fe3O4 nanoparticles (NPs) are of
great interest due to their potential as magnetic resonance imaging (MRI) and
upconversion luminescent (UCL) imaging agents, as well as near-infrared activated
photodynamic therapy (PDT) platforms. When C/S structured Fe3O4@Mn2+-doped
NaYF4:Yb/Er NPs were prepared previously, well-defined C/S-NPs could not be
formed without the doping of Mn2+ during synthesis. Here, the role of Mn2+ doping
on the synthesis of core-shell structured magnetic-upconversion nanoparticles
(MUCNPs) is investigated in detail. Core-shell-shell nanoparticles (C/S/S-MUCNPs)
with Fe3O4 as the core, an inert layer of Mn2+-doped NaYF4 and an outer shell
consisting of Mn2+-doped NaYF4:Yb/Er were prepared. To further develop C/S/S
MUCNPs applications in the biological field, amphiphilic poly(maleic anhydride
alt-1-octadecene) (C18PMH) modified with amine functionalized methoxy
poly(ethylene glycol) (C18PMH-mPEG) was used as a capping ligand to modify the
surface of C/S/S-MUCNPs to improve biocompatibility. UCL imaging, T1-weighted MRI
ascribed to the Mn2+ ions and T2-weighted MRI ascribed to the Fe3O4 core of C/S/S
MUCNPs were then evaluated. Finally, chlorine e6 (Ce6) was loaded on the C/S/S
MUCNPs and the PDT performance of these NPs was explored. Mn2+ doping is an
effective method to control the formation of core-shell structured MUCNPs, which
would be potential candidate as multifunctional nanoprobes for future T1/T2
weighted MR/UCL imaging and PDT platforms.
PMID- 29949935
TI - Blue-Light-Excited Eu3+/Sm3+ Co-Doped NaLa(MoO4)2 Phosphors: Synthesis,
Characterizations and Red Emission Enhancement for WLEDs.
AB - The system NaLa(MoO4)2:Eu3+/Sm3+ phosphors were prepared by solid-state reaction
followed by heat treatment at 450-600 °C. As shown by X-ray powder
diffraction, the phosphors had a body-centered tetragonal structure, high phase
purity and high crystallinity. The photoluminescence measurements carried out
under excitation at 464 nm indicated the main emission at about 615 nm
corresponding to the electric dipole transition 5D0→7F2 of Eu3+, which
agreed well with the emission wavelengths of the GaN-based blue LED chips. In
NaLa(MoO4)2:Eu3+/Sm3+ phosphors, Sm3+ can efficiently transfer excitation energy
to Eu3+, which resulted in a significant improvement of the fluorescence
intensity, and the fluorescence intensity of the phosphors calcined at 550 °C
maximized at the doping concentrations of Eu3+ and Sm3+ of 15.0 and 2.0 mol %,
respectively. The decay curves and CIE (Commission Internationale de L’
Eclairage) coordinates of Sm3+ or/and Eu3+ doped phosphors were analyzed for the
investigation of the energy transfer mechanism and color variation trend. Thus,
NaLa(MoO4)2:Eu3+,Sm3+ can be classified as a potential red-emitting phosphor for
white light-emitting diodes (WLEDs).
PMID- 29949934
TI - Fusogenic Viruses in Oncolytic Immunotherapy.
AB - Oncolytic viruses are under intense development and have earned their place among
the novel class of cancer immunotherapeutics that are changing the face of cancer
therapy. Their ability to specifically infect and efficiently kill tumor cells,
while breaking immune tolerance and mediating immune responses directed against
the tumor, make oncolytic viruses highly attractive candidates for immunotherapy.
Increasing evidence indicates that a subclass of oncolytic viruses, which encodes
for fusion proteins, could outperform non-fusogenic viruses, both in their direct
oncolytic potential, as well as their immune-stimulatory properties. Tumor cell
infection with these viruses leads to characteristic syncytia formation and cell
death due to fusion, as infected cells become fused with neighboring cells, which
promotes intratumoral spread of the infection and releases additional immunogenic
signals. In this review, we discuss the potential of fusogenic oncolytic viruses
as optimal candidates to enhance immunotherapy and initiate broad antitumor
responses. We provide an overview of the cytopathic mechanism of syncytia
formation through viral-mediated expression of fusion proteins, either endogenous
or engineered, and their benefits for cancer therapy. Growing evidence indicates
that fusogenicity could be an important feature to consider in the design of
optimal oncolytic virus platforms for combinatorial oncolytic immunotherapy.
PMID- 29949937
TI - Childhood and Adolescence Cancers in the Palermo Province (Southern Italy): Ten
Years (2003-2012) of Epidemiological Surveillance.
AB - Italy has one of the highest paediatric cancer incidence rates in Europe. We
compared cancer incidence and survival rates in children (0-14 years) and
adolescents (15-19 years) residing in Palermo Province (PP) with statistics
derived from Italian and European surveillance systems. We included all incident
cancer cases, malignant tumours and non-malignant neoplasm of central nervous
system (benign and uncertain whether malignant or benign), detected in children
and adolescents by the Palermo Province Cancer Registry (PPCR) between 2003 and
2012. A jointpoint regression model was applied. Annual Average Percentage
Changes were calculated. The Besag-York-Mollie model was used to detect any
cluster. The 5-year survival analysis was computed using Kaplan-Meier and
actuarial methods. We identified 555 paediatric cancer incident cases (90%
“malignant tumours”). No difference in incidence rates was
highlighted between PPCR and Italy 26 registries and between PPCR and Southern
Europe. No jointpoint or significant trend was identified and no cluster was
detected. The 5-year overall survival didn’t differ between PP and the
Italian AIRTUM pool. A borderline higher statistically significant survival was
observed in age-group 1-4 when comparing PPCR to EUROCARE-5. The epidemiological
surveillance documented in the PP was a paediatric cancer burden in line with
Italy and southern Europe. The study supports the supplementary role of general
population-based cancer registries to provide paediatric cancer surveillance of
local communities.
PMID- 29949936
TI - Glutathione in Ovarian Cancer: A Double-Edged Sword.
AB - Glutathione (GSH) has several roles in a cell, such as a reactive oxygen species
(ROS) scavenger, an intervenient in xenobiotics metabolism and a reservoir of
cysteine. All of these activities are important in the maintenance of normal
cells homeostasis but can also constitute an advantage for cancer cells, allowing
disease progression and resistance to therapy. Ovarian cancer is the major cause
of death from gynaecologic disease and the second most common gynaecologic
malignancy worldwide. In over 50 years, the overall survival of patients
diagnosed with epithelial ovarian cancer has not changed, regardless of the
efforts concerning early detection, radical surgery and new therapeutic
approaches. Late diagnosis and resistance to therapy are the main causes of this
outcome, and GSH is profoundly associated with chemoresistance to platinum salts,
which, together with taxane-based chemotherapy and surgery, are the main therapy
strategies in ovarian cancer treatment. Herein, we present some insights into the
role of GSH in the poor prognosis of ovarian cancer, and also point out how some
strategies underlying the dependence of ovarian cancer cells on GSH can be
further used to improve the effectiveness of therapy.
PMID- 29949938
TI - DNA and Protein Analyses to Confirm the Absence of Cross-Contamination and
Support the Clinical Reliability of Extensively Hydrolysed Diets for Adverse Food
Reaction-Pets.
AB - Adverse food reactions (AFR) are a common cause of skin diseases in cats and
dogs. The correct diagnosis and management of AFR relies upon clinical nutrition.
The reliability of commercial hypoallergenic diets commonly used in AFR has been
questioned because studies have shown the presence of proteins not declared on
the label ingredients. It is proposed that extensively hydrolysed protein-based
diets constitute a reliable nutritional solution. Royal Canin Anallergenic™
Canine and Feline diets are formulated with very low molecular weight feather
protein and purified corn starch. Protein gel electrophoresis and thin layer
paper chromatography were used to characterize protein hydrolysis in these diets
and their hydrolysed raw materials; protein species were identified by mass
spectrometry. To detect cross-contaminating protein, species-specific DNA was
measured and correlated with ancillary protein content using calibration curves.
The only protein components detected in the extensively hydrolysed feather
protein raw material were amino acids and small oligopeptides. GBSS-I (Granule
bound starch synthase 1) was detected in the finished diets; this has not been
reported as a clinically apparent allergen in dogs or cats. The DNA threshold
corresponding to the maximum acceptable level of ancillary protein was not
exceeded in 99.9% of more than 2150 product batches tested and no products were
released to the market with cross-contaminating proteins. These results
demonstrate the extensive level of protein hydrolysis in Royal Canin
Anallergenic™ Canine and Feline diets and the absence of cross
contaminating protein, both key requirements for a diet to be used during
diagnosis and for management of pets with AFR.
PMID- 29949939
TI - The Transcription Factor ZafA Regulates the Homeostatic and Adaptive Response to
Zinc Starvation in Aspergillus fumigatus.
AB - One of the most important features that enables Aspergillus fumigatus to grow
within a susceptible individual and to cause disease is its ability to obtain
Zn2+ ions from the extremely zinc-limited environment provided by host tissues.
Zinc uptake from this source in A. fumigatus relies on ZIP transporters encoded
by the zrfA, zrfB and zrfC genes. The expression of these genes is tightly
regulated by the ZafA transcription factor that regulates zinc homeostasis and is
essential for A. fumigatus virulence. We combined the use of microarrays,
Electrophoretic Mobility Shift Assays (EMSA) analyses, DNase I footprinting
assays and in silico tools to better understand the regulation of the homeostatic
and adaptive response of A. fumigatus to zinc starvation. We found that under
zinc-limiting conditions, ZafA functions mainly as a transcriptional activator
through binding to a zinc response sequence located in the regulatory regions of
its target genes, although it could also function as a repressor of a limited
number of genes. In addition to genes involved in the homeostatic response to
zinc deficiency, ZafA also influenced, either directly or indirectly, the
expression of many other genes. It is remarkable that the expression of many
genes involved in iron uptake and ergosterol biosynthesis is strongly reduced
under zinc starvation, even though only the expression of some of these genes
appeared to be influenced directly or indirectly by ZafA. In addition, it appears
to exist in A. fumigatus a zinc/iron cross-homeostatic network to allow the
adaptation of the fungus to grow in media containing unbalanced Zn:Fe ratios. The
adaptive response to oxidative stress typically linked to zinc starvation was
also mediated by ZafA, as was the strong induction of genes involved in gliotoxin
biosynthesis and self-protection against endogenous gliotoxin. This study has
expanded our knowledge about the regulatory and metabolic changes displayed by A.
fumigatus in response to zinc starvation and has helped us to pinpoint new ZafA
target genes that could be important for fungal pathogens to survive and grow
within host tissues and, hence, for virulence.
PMID- 29949941
TI - Pharmacy Practice and Education in Austria.
AB - The PHARMINE (“Pharmacy Education in Europe”) project studied
pharmacy practice and education in the European Union (EU) member states. The
work was carried out using an electronic survey sent to chosen pharmacy
representatives. The surveys of the individual member states are now being
published as reference documents for students and staff interested in research on
pharmacy education in the EU and in mobility. This paper presents the results of
the PHARMINE survey on pharmacy practice and education in Austria. In the light
of this, we examine the harmonisation of practice and education in Austria with
EU norms.
PMID- 29949940
TI - Salicylic Acid Induces Resistance in Rubber Tree against Phytophthora palmivora.
AB - Induced resistance by elicitors is considered to be an eco-friendly strategy to
stimulate plant defense against pathogen attack. In this study, we elucidated the
effect of salicylic acid (SA) on induced resistance in rubber tree against
Phytophthora palmivora and evaluated the possible defense mechanisms that were
involved. For SA pretreatment, rubber tree exhibited a significant reduction in
disease severity by 41%. Consistent with the occurrence of induced resistance,
the pronounced increase in H2O2 level, catalase (CAT) and peroxidase (POD)
activities were observed. For defense reactions, exogenous SA promoted the
increases of H2O2, CAT, POD and phenylalanine ammonia lyase (PAL) activities,
including lignin, endogenous SA and scopoletin (Scp) contents. However, SA had
different effects on the activity of each CAT isoform in the particular rubber
tree organs. Besides, three partial cDNAs encoding CAT (HbCAT1, HbCAT2 and
HbCAT3) and a partial cDNA encoding PAL (HbPAL) were isolated from rubber tree.
Moreover, the expressions of HbCAT1, HbPAL and HbPR1 were induced by SA. Our
findings suggested that, upon SA priming, the elevated H2O2, CAT, POD and PAL
activities, lignin, endogenous SA and Scp contents, including the up-regulated
HbCAT1, HbPAL and HbPR1 expressions could potentiate the resistance in rubber
tree against P. palmivora.
PMID- 29949942
TI - Neutralizing Anti-Hemagglutinin Monoclonal Antibodies Induced by Gene-Based
Transfer Have Prophylactic and Therapeutic Effects on Influenza Virus Infection.
AB - Hemagglutinin (HA) of influenza virus is a major target for vaccines. HA
initiates the internalization of the virus into the host cell by binding to host
sialic acid receptors; therefore, inhibition of HA can significantly prevent
influenza virus infection. However, the high diversity of HA permits the
influenza virus to escape from host immunity. Moreover, the vaccine efficacy is
poor in some high-risk populations (e.g., elderly or immunocompromised patients).
Passive immunization with anti-HA monoclonal antibodies (mAbs) is an attractive
therapy; however, this method has high production costs and requires repeated
inoculations. To address these issues, several methods for long-term expression
of mAb against influenza virus have been developed. Here, we provide an overview
of methods using plasmid and viral adeno-associated virus (AAV) vectors that have
been modified for higher expression of neutralizing antibodies in the host. We
also examine two methods of injection, electro-transfer and hydrodynamic
injection. Our results show that antibody gene transfer is effective against
influenza virus infection even in immunocompromised mice, and antibody expression
was detected in the serum and upper respiratory tract. We also demonstrate this
method to be effective following influenza virus infection. Finally, we discuss
the perspective of passive immunization with antibody gene transfer for future
clinical trials.
PMID- 29949943
TI - Treatment of Nanocellulose by Submerged Liquid Plasma for Surface
Functionalization.
AB - Tailoring the surface properties of nanocellulose to improve the compatibility of
components in polymer nanocomposites is of great interest. In this work,
dispersions of nanocellulose in water and acetonitrile were functionalized by
submerged plasmas, with the aim of increasing the quality of this reinforcing
agent in biopolymer composite materials. Both the morphology and surface
chemistry of nanocellulose were influenced by the application of a plasma torch
and filamentary jet plasma in a liquid suspension of nanocellulose. Depending on
the type of plasma source and gas mixture the surface chemistry was modified by
the incorporation of oxygen and nitrogen containing functional groups. The
treatment conditions which lead to nanocellulose based polymer nanocomposites
with superior mechanical properties were identified. This work provides a new eco
friendly method for the surface functionalization of nanocellulose directly in
water suspension, thus overcoming the disadvantages of chemical treatments.
PMID- 29949945
TI - Forced Expression of Foxg1 in the Cortical Hem Leads to the Transformation of
Cajal-Retzius Cells into Dentate Granule Neurons.
AB - The Wnt- and BMP-rich cortical hem has been demonstrated to be critical for the
pattern formation of the telencephalon, and it is particularly important for the
induction of the hippocampus. Meanwhile, the cortical hem is one of the sources
of Cajal-Retzius cells. Many Cajal-Retzius cells are produced in the hem and
populated to the media-caudal surface of the telencephalon. However, the
mechanism of the maintenance of the hem remain unclear. In this study, we
generated a transgenic mouse line CAG-loxp-stop-loxp-Foxg1-IRES-EGFP. By crossing
Fzd10CreERTM with this line, combined with tamoxifen induction, Foxg1 was
ectopically expressed in the hem from embryonic day 10.5 (E10.5) onwards. We have
found the hem-derived Cajal-Retzius cells were transformed into dentate granule
neurons accompanied with ectopic expression of Lhx2. However, the morphology of
the hem displayed no obvious changes. The hem specific markers, Wnt3a and Wnt2b,
were slightly downregulated. Our results indicate that Foxg1 is sufficient to
induce the expression of Lhx2 in the dorsal part of the hem. The ectopic Lhx2 and
decreased Wnt signals may both contribute to the cell fate switch. Our study
provides new insight into the mechanism underlying the maintenance of the hem.
PMID- 29949944
TI - Investigating the Promoter of FAT10 Gene in HCC Patients.
AB - FAT10, which is also known as diubiquitin, has been implicated to play important
roles in immune regulation and tumorigenesis. Its expression is up-regulated in
the tumors of Hepatocellular Carcinoma (HCC) and other cancer patients. High
levels of FAT10 in cells have been shown to result in increased mitotic non
disjunction and chromosome instability, leading to tumorigenesis. To evaluate
whether the aberrant up-regulation of the FAT10 gene in the tumors of HCC
patients is due to mutations or the aberrant methylation of CG dinucleotides at
the FAT10 promoter, sequencing and methylation-specific sequencing of the
promoter of FAT10 was performed. No mutations were found that could explain the
differential expression of FAT10 between the tumor and non-tumorous tissues of
HCC patients. However, six single nucleotide polymorphisms (SNPs), including one
that has not been previously reported, were identified at the promoter of the
FAT10 gene. Different haplotypes of these SNPs were found to significantly
mediate different FAT10 promoter activities. Consistent with the experimental
observation, differential FAT10 expression in the tumors of HCC patients carrying
haplotype 1 was generally higher than those carrying haplotype II. Notably, the
methylation status of this promoter was found to correlate with FAT10 expression
levels. Hence, the aberrant overexpression of the FAT10 gene in the tumors of HCC
patients is likely due to aberrant methylation, rather than mutations at the
FAT10 promoter.
PMID- 29949946
TI - Effects of Moringa oleifera Leaves Extract on High Glucose-Induced Metabolic
Changes in HepG2 Cells.
AB - Mitochondrial dysfunction is a hallmark of diabetes, but the metabolic
alterations during early stages of the disease remain unknown. The ability of
liver cells to rearrange their metabolism plays an important role in compensating
the energy shortage and may provide cell survival. Moringa oleifera leaves have
been studied for its health properties against diabetes, insulin resistance, and
non-alcoholic liver disease. We postulated that M. oleifera executes a protective
function on mitochondrial functionality in HepG2 treated with high glucose. We
evaluated the effect of high glucose treatment on the mitochondrial function of
HepG2 cells using a Seahorse extracellular flux analyzer (Agilent, Santa Clara,
CA, USA), blue native polyacrylamide gel electrophoresis (BN-PAGE), and western
blot analysis. For assessment of mitochondrial abnormalities, we measured the
activity of mitochondrial Complex I and IV as well as uncoupling protein 2, and
sirtuin 3 protein contents. Our results demonstrate that, under conditions
mimicking the hyperglycemia, Complex I activity, UCP2, Complex III and IV
subunits content, supercomplex formation, and acetylation levels are modified
with respect to the control condition. However, basal oxygen consumption rate was
not affected and mitochondrial reactive oxygen species production remained
unchanged in all groups. Treatment of HepG2 cells with M. oleifera extract
significantly increased both protein content and mitochondrial complexes
activities. Nonetheless, control cells’ respiratory control ratio (RCR) was
4.37 compared to high glucose treated cells’ RCR of 15.3, and glucose plus
M. oleifera treated cells’ RCR of 5.2, this indicates high-quality
mitochondria and efficient oxidative phosphorylation coupling. Additionally, the
state app was not altered between different treatments, suggesting no alteration
in respiratory fluxes. These findings enhance understanding of the actions of M.
oleifera and suggest that the known antidiabetic property of this plant, at least
in part, is mediated through modulating the mitochondrial respiratory chain.
PMID- 29949947
TI - Insights into Structure-Activity Relationships of 3-Arylhydrazonoindolin-2-One
Derivatives for Their Multitarget Activity on beta-Amyloid Aggregation and
Neurotoxicity.
AB - Despite the controversial outcomes of clinical trials executed so far, the
prevention of β-amyloid (Aβ) deposition and neurotoxicity by small
molecule inhibitors of Aβ aggregation remains a target intensively pursued
in the search of effective drugs for treating Alzheimer’s disease (AD) and
related neurodegeneration syndromes. As a continuation of previous studies, a
series of new 3-(2-arylhydrazono)indolin-2-one derivatives was synthesized and
assayed, investigating the effects of substitutions on both the indole core and
arylhydrazone moiety. Compared with the reference compound 1, we disclosed
equipotent derivatives bearing alkyl substituents at the indole nitrogen, and
fairly tolerated bioisosteric replacements at the arylhydrazone moiety. For most
of the investigated compounds, the inhibition of Aβ40 aggregation (expressed
as pIC50) was found to be correlated with lipophilicity, as assessed by a
reversed-phase HPLC method, through a bilinear relationship. The N1-cyclopropyl
derivative 28 was tested in cell-based assays of Aβ42 oligomer toxicity and
oxidative stress induced by hydrogen peroxide, showing significant cytoprotective
effects. This study confirmed the versatility of isatin in preparing multitarget
small molecules affecting different biochemical pathways involved in AD.
PMID- 29949948
TI - HyTexiLa: High Resolution Visible and Near Infrared Hyperspectral Texture Images.
AB - We present a dataset of close range hyperspectral images of materials that span
the visible and near infrared spectrums: HyTexiLa (Hyperspectral Texture images
acquired in Laboratory). The data is intended to provide high spectral and
spatial resolution reflectance images of 112 materials to study spatial and
spectral textures. In this paper we discuss the calibration of the data and the
method for addressing the distortions during image acquisition. We provide a
spectral analysis based on non-negative matrix factorization to quantify the
spectral complexity of the samples and extend local binary pattern operators to
the hyperspectral texture analysis. The results demonstrate that although the
spectral complexity of each of the textures is generally low, increasing the
number of bands permits better texture classification, with the opponent band
local binary pattern feature giving the best performance.
PMID- 29949950
TI - Online Model Updating and Dynamic Learning Rate-Based Robust Object Tracking.
AB - Robust visual tracking is a significant and challenging issue in computer vision
related research fields and has attracted an immense amount of attention from
researchers. Due to various practical applications, many studies have been done
that have introduced numerous algorithms. It is considered to be a challenging
problem due to the unpredictability of various real-time situations, such as
illumination variations, occlusion, fast motion, deformation, and scale
variation, even though we only know the initial target position. To address these
matters, we used a kernelized-correlation-filter-based translation filter with
the integration of multiple features such as histogram of oriented gradients
(HOG) and color attributes. These powerful features are useful to differentiate
the target from the surrounding background and are effective for motion blur and
illumination variations. To minimize the scale variation problem, we designed a
correlation-filter-based scale filter. The proposed adaptive model’s
updating and dynamic learning rate strategies based on a peak-to-sidelobe ratio
effectively reduce model-drifting problems by avoiding noisy appearance changes.
The experiment results show that our method provides the best performance
compared to other methods, with a distance precision score of 79.9%, overlap
success score of 59.0%, and an average running speed of 74 frames per second on
the object tracking benchmark (OTB-2015).
PMID- 29949949
TI - NF-kappaB Regulates Redox Status in Breast Cancer Subtypes.
AB - Oxidative stress (OS) is an indispensable condition to ensure genomic instability
in cancer cells. In breast cancer (BC), redox alterations have been widely
characterized, but since this process results from a chain of inflammatory
events, the causal molecular triggers remain to be identified. In this context,
we used a microarray approach to investigate the role of the main pro-oxidant
transcription factor, nuclear factor-kappa B (NF-kappaB), in gene profiles of BC
subtypes. Our results showed that NF-kappaB knockdown in distinct BC subtypes led
to differential expression of relevant factors involved in glutathione
metabolism, prostaglandins, cytochrome P450 and cyclooxygenase, suggesting a
relationship between the redox balance and NF-kappaB in such cells. In addition,
we performed biochemical analyses to validate the microarray dataset focusing on
OS and correlated these parameters with normal expression or NF-kappaB
inhibition. Our data showed a distinct oxidative status pattern for each of the
three studied BC subtype models, consistent with the intrinsic characteristics of
each BC subtype. Thus, our findings suggest that NF-kappaB may represent an
additional mechanism related to OS maintenance in BC, operating in various forms
to mediate other important predominant signaling components of each BC subtype.
PMID- 29949952
TI - PartsGenie: an integrated tool for optimizing and sharing synthetic biology
parts.
AB - Motivation: Synthetic biology is typified by developing novel genetic constructs
from the assembly of reusable synthetic DNA parts, which contain one or more
features such as promoters, ribosome binding sites, coding sequences and
terminators. PartsGenie is introduced to facilitate the computational design of
such synthetic biology parts, bridging the gap between optimization tools for the
design of novel parts, the representation of such parts in community-developed
data standards such as Synthetic Biology Open Language, and their sharing in
journal-recommended data repositories. Consisting of a drag-and-drop web
interface, a number of DNA optimization algorithms, and an interface to the well
used data repository JBEI ICE, PartsGenie facilitates the design, optimization
and dissemination of reusable synthetic biology parts through an integrated
application. Availability and implementation: PartsGenie is freely available at
https://parts.synbiochem.co.uk.
PMID- 29949951
TI - Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New
Isoxazole Derivative.
AB - This work describes the synthesis of a new series of isoxazole derivatives, their
immunosuppressive properties, and the mechanism of action of a representative
compound. A new series of N′-substituted derivatives of 5-amino-N,3
dimethyl-1,2-oxazole-4-carbohydrazide (MM1-MM10) was synthesized in reaction of 5
amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds.
The isoxazole derivatives were tested in several in vitro models using human
cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation
of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of
the compounds with regard to a reference A549 cell line was also differential. 5
amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4
carbohydrazide (MM3) compound was selected for further investigation because of
its lack of toxicity and because it had the strongest antiproliferative activity.
The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis
factor (TNF α) production in human whole blood cell cultures. In the model
of Jurkat cells, MM3 elicited strong increases in the expression of caspases,
Fas, and NF-κB1, indicating that a proapoptotic action may account for its
immunosuppressive action in the studied models.
PMID- 29949953
TI - MARSI: metabolite analogues for rational strain improvement.
AB - Summary: Metabolite analogues (MAs) mimic the structure of native metabolites,
can competitively inhibit their utilization in enzymatic reactions, and are
commonly used as selection tools for isolating desirable mutants of industrial
microorganisms. Genome-scale metabolic models representing all biochemical
reactions in an organism can be used to predict effects of MAs on cellular
phenotypes. Here, we present the metabolite analogues for rational strain
improvement (MARSI) framework. MARSI provides a rational approach to strain
improvement by searching for metabolites as targets instead of genes or
reactions. The designs found by MARSI can be implemented by supplying MAs in the
culture media, enabling metabolic rewiring without the use of recombinant DNA
technologies that cannot always be used due to regulations. To facilitate
experimental implementation, MARSI provides tools to identify candidate MAs to a
target metabolite from a database of known drugs and analogues. Availability and
implementation: The code is freely available at
https://github.com/biosustain/marsi under the Apache License V2. MARSI is
implemented in Python. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29949954
TI - nVenn: generalized, quasi-proportional Venn and Euler diagrams.
AB - Motivation: Venn and Euler diagrams are extensively used for the visualization of
relationships between experiments and datasets. However, representing more than
three datasets while keeping the proportions of each region is still not feasible
with existing tools. Results: We present an algorithm to render all the regions
of a generalized n-dimensional Venn diagram, while keeping the area of each
region approximately proportional to the number of elements included. In
addition, missing regions in Euler diagrams lead to simplified representations.
The algorithm generates an n-dimensional Venn diagram and inserts circles of
given areas in each region. Then, the diagram is rearranged with a dynamic, self
correcting simulation in which each set border is contracted until it contacts
the circles inside. This algorithm is implemented in a C++ tool (nVenn) with or
without a web interface. The web interface also provides the ability to analyze
the regions of the diagram. Availability and implementation: The source code and
pre-compiled binaries of nVenn are available at https://github.com/vqf/nVenn. A
web interface for up to six sets can be accessed at
http://degradome.uniovi.es/cgi-bin/nVenn/nvenn.cgi. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29949955
TI - BEL2ABM: agent-based simulation of static models in Biological Expression
Language.
AB - Summary: While cause-and-effect knowledge assembly models encoded in Biological
Expression Language are able to support generation of mechanistic hypotheses,
they are static and limited in their ability to encode temporality. Here, we
present BEL2ABM, a software for producing continuous, dynamic, executable agent
based models from BEL templates. Availability and implementation: The tool has
been developed in Java and NetLogo. Code, data and documentation are available
under the Apache 2.0 License at https://github.com/pybel/bel2abm. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29949956
TI - AmpUMI: design and analysis of unique molecular identifiers for deep amplicon
sequencing.
AB - Motivation: Unique molecular identifiers (UMIs) are added to DNA fragments before
PCR amplification to discriminate between alleles arising from the same genomic
locus and sequencing reads produced by PCR amplification. While computational
methods have been developed to take into account UMI information in genome-wide
and single-cell sequencing studies, they are not designed for modern amplicon
based sequencing experiments, especially in cases of high allelic diversity.
Importantly, no guidelines are provided for the design of optimal UMI length for
amplicon-based sequencing experiments. Results: Based on the total number of DNA
fragments and the distribution of allele frequencies, we present a model for the
determination of the minimum UMI length required to prevent UMI collisions and
reduce allelic distortion. We also introduce a user-friendly software tool called
AmpUMI to assist in the design and the analysis of UMI-based amplicon sequencing
studies. AmpUMI provides quality control metrics on frequency and quality of
UMIs, and trims and deduplicates amplicon sequences with user specified
parameters for use in downstream analysis. Availability and implementation:
AmpUMI is open-source and freely available at
http://github.com/pinellolab/AmpUMI.
PMID- 29949957
TI - A novel methodology on distributed representations of proteins using their
interacting ligands.
AB - Motivation: The effective representation of proteins is a crucial task that
directly affects the performance of many bioinformatics problems. Related
proteins usually bind to similar ligands. Chemical characteristics of ligands are
known to capture the functional and mechanistic properties of proteins suggesting
that a ligand-based approach can be utilized in protein representation. In this
study, we propose SMILESVec, a Simplified molecular input line entry system
(SMILES)-based method to represent ligands and a novel method to compute
similarity of proteins by describing them based on their ligands. The proteins
are defined utilizing the word-embeddings of the SMILES strings of their ligands.
The performance of the proposed protein description method is evaluated in
protein clustering task using TransClust and MCL algorithms. Two other protein
representation methods that utilize protein sequence, Basic local alignment tool
and ProtVec, and two compound fingerprint-based protein representation methods
are compared. Results: We showed that ligand-based protein representation, which
uses only SMILES strings of the ligands that proteins bind to, performs as well
as protein sequence-based representation methods in protein clustering. The
results suggest that ligand-based protein description can be an alternative to
the traditional sequence or structure-based representation of proteins and this
novel approach can be applied to different bioinformatics problems such as
prediction of new protein-ligand interactions and protein function annotation.
Availability and implementation:
https://github.com/hkmztrk/SMILESVecProteinRepresentation. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29949958
TI - A unifying framework for joint trait analysis under a non-infinitesimal model.
AB - Motivation: A large proportion of risk regions identified by genome-wide
association studies (GWAS) are shared across multiple diseases and traits.
Understanding whether this clustering is due to sharing of causal variants or
chance colocalization can provide insights into shared etiology of complex traits
and diseases. Results: In this work, we propose a flexible, unifying framework to
quantify the overlap between a pair of traits called UNITY (Unifying Non
Infinitesimal Trait analYsis). We formulate a Bayesian generative model that
relates the overlap between pairs of traits to GWAS summary statistic data under
a non-infinitesimal genetic architecture underlying each trait. We propose a
Metropolis-Hastings sampler to compute the posterior density of the genetic
overlap parameters in this model. We validate our method through comprehensive
simulations and analyze summary statistics from height and body mass index GWAS
to show that it produces estimates consistent with the known genetic makeup of
both traits. Availability and implementation: The UNITY software is made freely
available to the research community at: https://github.com/bogdanlab/UNITY.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29949959
TI - COSSMO: predicting competitive alternative splice site selection using deep
learning.
AB - Motivation: Alternative splice site selection is inherently competitive and the
probability of a given splice site to be used also depends on the strength of
neighboring sites. Here, we present a new model named the competitive splice site
model (COSSMO), which explicitly accounts for these competitive effects and
predicts the percent selected index (PSI) distribution over any number of
putative splice sites. We model an alternative splicing event as the choice of a
3' acceptor site conditional on a fixed upstream 5' donor site or the choice of a
5' donor site conditional on a fixed 3' acceptor site. We build four different
architectures that use convolutional layers, communication layers, long short
term memory and residual networks, respectively, to learn relevant motifs from
sequence alone. We also construct a new dataset from genome annotations and RNA
Seq read data that we use to train our model. Results: COSSMO is able to predict
the most frequently used splice site with an accuracy of 70% on unseen test data,
and achieve an R2 of 0.6 in modeling the PSI distribution. We visualize the
motifs that COSSMO learns from sequence and show that COSSMO recognizes the
consensus splice site sequences and many known splicing factors with high
specificity. Availability and implementation: Model predictions, our training
dataset, and code are available from http://cossmo.genes.toronto.edu.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29949960
TI - aliFreeFold: an alignment-free approach to predict secondary structure from
homologous RNA sequences.
AB - Motivation: Predicting the conserved secondary structure of homologous
ribonucleic acid (RNA) sequences is crucial for understanding RNA functions.
However, fast and accurate RNA structure prediction is challenging, especially
when the number and the divergence of homologous RNA increases. To address this
challenge, we propose aliFreeFold, based on a novel alignment-free approach which
computes a representative structure from a set of homologous RNA sequences using
sub-optimal secondary structures generated for each sequence. It is based on a
vector representation of sub-optimal structures capturing structure conservation
signals by weighting structural motifs according to their conservation across the
sub-optimal structures. Results: We demonstrate that aliFreeFold provides a good
balance between speed and accuracy regarding predictions of representative
structures for sets of homologous RNA compared to traditional methods based on
sequence and structure alignment. We show that aliFreeFold is capable of
uncovering conserved structural features fastly and effectively thanks to its
weighting scheme that gives more (resp. less) importance to common (resp.
uncommon) structural motifs. The weighting scheme is also shown to be capable of
capturing conservation signal as the number of homologous RNA increases. These
results demonstrate the ability of aliFreefold to efficiently and accurately
provide interesting structural representatives of RNA families. Availability and
implementation: aliFreeFold was implemented in C++. Source code and Linux binary
are freely available at https://github.com/UdeS-CoBIUS/aliFreeFold. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29949961
TI - DisruPPI: structure-based computational redesign algorithm for protein binding
disruption.
AB - Motivation: Disruption of protein-protein interactions can mitigate antibody
recognition of therapeutic proteins, yield monomeric forms of oligomeric
proteins, and elucidate signaling mechanisms, among other applications. While
designing affinity-enhancing mutations remains generally quite challenging, both
statistically and physically based computational methods can precisely identify
affinity-reducing mutations. In order to leverage this ability to design variants
of a target protein with disrupted interactions, we developed the DisruPPI
protein design method (DISRUpting Protein-Protein Interactions) to optimize
combinations of mutations simultaneously for both disruption and stability, so
that incorporated disruptive mutations do not inadvertently affect the target
protein adversely. Results: Two existing methods for predicting mutational
effects on binding, FoldX and INT5, were demonstrated to be quite precise in
selecting disruptive mutations from the SKEMPI and AB-Bind databases of
experimentally determined changes in binding free energy. DisruPPI was
implemented to use an INT5-based disruption score integrated with an AMBER-based
stability assessment and was applied to disrupt protein interactions in a set of
different targets representing diverse applications. In retrospective evaluation
with three different case studies, comparison of DisruPPI-designed variants to
published experimental data showed that DisruPPI was able to identify more
diverse interaction-disrupting and stability-preserving variants more efficiently
and effectively than previous approaches. In prospective application to an
interaction between enhanced green fluorescent protein (EGFP) and a nanobody,
DisruPPI was used to design five EGFP variants, all of which were shown to have
significantly reduced nanobody binding while maintaining function and
thermostability. This demonstrates that DisruPPI may be readily utilized for
effective removal of known epitopes of therapeutically relevant proteins.
Availability and implementation: DisruPPI is implemented in the EpiSweep package,
freely available under an academic use license. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29949962
TI - PrimAlign: PageRank-inspired Markovian alignment for large biological networks.
AB - Motivation: Cross-species analysis of large-scale protein-protein interaction
(PPI) networks has played a significant role in understanding the principles
deriving evolution of cellular organizations and functions. Recently, network
alignment algorithms have been proposed to predict conserved interactions and
functions of proteins. These approaches are based on the notion that orthologous
proteins across species are sequentially similar and that topology of PPIs
between orthologs is often conserved. However, high accuracy and scalability of
network alignment are still a challenge. Results: We propose a novel pairwise
global network alignment algorithm, called PrimAlign, which is modeled as a
Markov chain and iteratively transited until convergence. The proposed algorithm
also incorporates the principles of PageRank. This approach is evaluated on tasks
with human, yeast and fruit fly PPI networks. The experimental results
demonstrate that PrimAlign outperforms several prevalent methods with
statistically significant differences in multiple evaluation measures. PrimAlign,
which is multi-platform, achieves superior performance in runtime with its linear
asymptotic time complexity. Further evaluation is done with synthetic networks
and results suggest that popular topological measures do not reflect real
precision of alignments. Availability and implementation: The source code is
available at http://web.ecs.baylor.edu/faculty/cho/PrimAlign. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29949963
TI - Quantifying the similarity of topological domains across normal and cancer human
cell types.
AB - Motivation: Three-dimensional chromosome structure has been increasingly shown to
influence various levels of cellular and genomic functions. Through Hi-C data,
which maps contact frequency on chromosomes, it has been found that structural
elements termed topologically associating domains (TADs) are involved in many
regulatory mechanisms. However, we have little understanding of the level of
similarity or variability of chromosome structure across cell types and disease
states. In this study, we present a method to quantify resemblance and identify
structurally similar regions between any two sets of TADs. Results: We present an
analysis of 23 human Hi-C samples representing various tissue types in normal and
cancer cell lines. We quantify global and chromosome-level structural similarity,
and compare the relative similarity between cancer and non-cancer cells. We find
that cancer cells show higher structural variability around commonly mutated pan
cancer genes than normal cells at these same locations. Availability and
implementation: Software for the methods and analysis can be found at
https://github.com/Kingsford-Group/localtadsim.
PMID- 29949964
TI - Novo&Stitch: accurate reconciliation of genome assemblies via optical maps.
AB - Motivation: De novo genome assembly is a challenging computational problem due to
the high repetitive content of eukaryotic genomes and the imperfections of
sequencing technologies (i.e. sequencing errors, uneven sequencing coverage and
chimeric reads). Several assembly tools are currently available, each of which
has strengths and weaknesses in dealing with the trade-off between maximizing
contiguity and minimizing assembly errors (e.g. mis-joins). To obtain the best
possible assembly, it is common practice to generate multiple assemblies from
several assemblers and/or parameter settings and try to identify the highest
quality assembly. Unfortunately, often there is no assembly that both maximizes
contiguity and minimizes assembly errors, so one has to compromise one for the
other. Results: The concept of assembly reconciliation has been proposed as a way
to obtain a higher quality assembly by merging or reconciling all the available
assemblies. While several reconciliation methods have been introduced in the
literature, we have shown in one of our recent papers that none of them can
consistently produce assemblies that are better than the assemblies provided in
input. Here we introduce Novo&Stitch, a novel method that takes advantage of
optical maps to accurately carry out assembly reconciliation (assuming that the
assembled contigs are sufficiently long to be reliably aligned to the optical
maps, e.g. 50 Kbp or longer). Experimental results demonstrate that Novo&Stitch
can double the contiguity (N50) of the input assemblies without introducing mis
joins or reducing genome completeness. Availability and implementation:
Novo&Stitch can be obtained from https://github.com/ucrbioinfo/Novo_Stitch.
PMID- 29949965
TI - Bayesian networks for mass spectrometric metabolite identification via molecular
fingerprints.
AB - Motivation: Metabolites, small molecules that are involved in cellular reactions,
provide a direct functional signature of cellular state. Untargeted metabolomics
experiments usually rely on tandem mass spectrometry to identify the thousands of
compounds in a biological sample. Recently, we presented CSI:FingerID for
searching in molecular structure databases using tandem mass spectrometry data.
CSI:FingerID predicts a molecular fingerprint that encodes the structure of the
query compound, then uses this to search a molecular structure database such as
PubChem. Scoring of the predicted query fingerprint and deterministic target
fingerprints is carried out assuming independence between the molecular
properties constituting the fingerprint. Results: We present a scoring that takes
into account dependencies between molecular properties. As before, we predict
posterior probabilities of molecular properties using machine learning.
Dependencies between molecular properties are modeled as a Bayesian tree network;
the tree structure is estimated on the fly from the instance data. For each edge,
we also estimate the expected covariance between the two random variables. For
fixed marginal probabilities, we then estimate conditional probabilities using
the known covariance. Now, the corrected posterior probability of each candidate
can be computed, and candidates are ranked by this score. Modeling dependencies
improves identification rates of CSI:FingerID by 2.85 percentage points.
Availability and implementation: The new scoring Bayesian (fixed tree) is
integrated into SIRIUS 4.0 (https://bio.informatik.uni-jena.de/software/sirius/).
PMID- 29949966
TI - DeepFam: deep learning based alignment-free method for protein family modeling
and prediction.
AB - Motivation: A large number of newly sequenced proteins are generated by the next
generation sequencing technologies and the biochemical function assignment of the
proteins is an important task. However, biological experiments are too expensive
to characterize such a large number of protein sequences, thus protein function
prediction is primarily done by computational modeling methods, such as profile
Hidden Markov Model (pHMM) and k-mer based methods. Nevertheless, existing
methods have some limitations; k-mer based methods are not accurate enough to
assign protein functions and pHMM is not fast enough to handle large number of
protein sequences from numerous genome projects. Therefore, a more accurate and
faster protein function prediction method is needed. Results: In this paper, we
introduce DeepFam, an alignment-free method that can extract functional
information directly from sequences without the need of multiple sequence
alignments. In extensive experiments using the Clusters of Orthologous Groups
(COGs) and G protein-coupled receptor (GPCR) dataset, DeepFam achieved better
performance in terms of accuracy and runtime for predicting functions of proteins
compared to the state-of-the-art methods, both alignment-free and alignment-based
methods. Additionally, we showed that DeepFam has a power of capturing conserved
regions to model protein families. In fact, DeepFam was able to detect conserved
regions documented in the Prosite database while predicting functions of
proteins. Our deep learning method will be useful in characterizing functions of
the ever increasing protein sequences. Availability and implementation: Codes are
available at https://bhi-kimlab.github.io/DeepFam.
PMID- 29949967
TI - Gene prioritization using Bayesian matrix factorization with genomic and
phenotypic side information.
AB - Motivation: Most gene prioritization methods model each disease or phenotype
individually, but this fails to capture patterns common to several diseases or
phenotypes. To overcome this limitation, we formulate the gene prioritization
task as the factorization of a sparsely filled gene-phenotype matrix, where the
objective is to predict the unknown matrix entries. To deliver more accurate gene
phenotype matrix completion, we extend classical Bayesian matrix factorization to
work with multiple side information sources. The availability of side information
allows us to make non-trivial predictions for genes for which no previous disease
association is known. Results: Our gene prioritization method can innovatively
not only integrate data sources describing genes, but also data sources
describing Human Phenotype Ontology terms. Experimental results on our benchmarks
show that our proposed model can effectively improve accuracy over the well
established gene prioritization method, Endeavour. In particular, our proposed
method offers promising results on diseases of the nervous system; diseases of
the eye and adnexa; endocrine, nutritional and metabolic diseases; and congenital
malformations, deformations and chromosomal abnormalities, when compared to
Endeavour. Availability and implementation: The Bayesian data fusion method is
implemented as a Python/C++ package: https://github.com/jaak-s/macau. It is also
available as a Julia package: https://github.com/jaak-s/BayesianDataFusion.jl.
All data and benchmarks generated or analyzed during this study can be downloaded
at https://owncloud.esat.kuleuven.be/index.php/s/UGb89WfkZwMYoTn. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29949968
TI - A spectral clustering-based method for identifying clones from high-throughput B
cell repertoire sequencing data.
AB - Motivation: B cells derive their antigen-specificity through the expression of
Immunoglobulin (Ig) receptors on their surface. These receptors are initially
generated stochastically by somatic re-arrangement of the DNA and further
diversified following antigen-activation by a process of somatic hypermutation,
which introduces mainly point substitutions into the receptor DNA at a high rate.
Recent advances in next-generation sequencing have enabled large-scale profiling
of the B cell Ig repertoire from blood and tissue samples. A key computational
challenge in the analysis of these data is partitioning the sequences to identify
descendants of a common B cell (i.e. a clone). Current methods group sequences
using a fixed distance threshold, or a likelihood calculation that is
computationally-intensive. Here, we propose a new method based on spectral
clustering with an adaptive threshold to determine the local sequence
neighborhood. Validation using simulated and experimental datasets demonstrates
that this method has high sensitivity and specificity compared to a fixed
threshold that is optimized for these measures. In addition, this method works on
datasets where choosing an optimal fixed threshold is difficult and is more
computationally efficient in all cases. The ability to quickly and accurately
identify members of a clone from repertoire sequencing data will greatly improve
downstream analyses. Clonally-related sequences cannot be treated independently
in statistical models, and clonal partitions are used as the basis for the
calculation of diversity metrics, lineage reconstruction and selection analysis.
Thus, the spectral clustering-based method here represents an important
contribution to repertoire analysis. Availability and implementation: Source code
for this method is freely available in the SCOPe (Spectral Clustering for clOne
Partitioning) R package in the Immcantation framework: www.immcantation.org under
the CC BY-SA 4.0 license. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29949969
TI - Versatile genome assembly evaluation with QUAST-LG.
AB - Motivation: The emergence of high-throughput sequencing technologies
revolutionized genomics in early 2000s. The next revolution came with the era of
long-read sequencing. These technological advances along with novel computational
approaches became the next step towards the automatic pipelines capable to
assemble nearly complete mammalian-size genomes. Results: In this manuscript, we
demonstrate performance of the state-of-the-art genome assembly software on six
eukaryotic datasets sequenced using different technologies. To evaluate the
results, we developed QUAST-LG-a tool that compares large genomic de novo
assemblies against reference sequences and computes relevant quality metrics.
Since genomes generally cannot be reconstructed completely due to complex repeat
patterns and low coverage regions, we introduce a concept of upper bound assembly
for a given genome and set of reads, and compute theoretical limits on assembly
correctness and completeness. Using QUAST-LG, we show how close the assemblies
are to the theoretical optimum, and how far this optimum is from the finished
reference. Availability and implementation: http://cab.spbu.ru/software/quast-lg.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29949970
TI - A pan-genome-based machine learning approach for predicting antimicrobial
resistance activities of the Escherichia coli strains.
AB - Motivation: Antimicrobial resistance (AMR) is becoming a huge problem in both
developed and developing countries, and identifying strains resistant or
susceptible to certain antibiotics is essential in fighting against antibiotic
resistant pathogens. Whole-genome sequences have been collected for different
microbial strains in order to identify crucial characteristics that allow certain
strains to become resistant to antibiotics; however, a global inspection of the
gene content responsible for AMR activities remains to be done. Results: We
propose a pan-genome-based approach to characterize antibiotic-resistant
microbial strains and test this approach on the bacterial model organism
Escherichia coli. By identifying core and accessory gene clusters and predicting
AMR genes for the E. coli pan-genome, we not only showed that certain classes of
genes are unevenly distributed between the core and accessory parts of the pan
genome but also demonstrated that only a portion of the identified AMR genes
belong to the accessory genome. Application of machine learning algorithms to
predict whether specific strains were resistant to antibiotic drugs yielded the
best prediction accuracy for the set of AMR genes within the accessory part of
the pan-genome, suggesting that these gene clusters were most crucial to AMR
activities in E. coli. Selecting subsets of AMR genes for different antibiotic
drugs based on a genetic algorithm (GA) achieved better prediction performances
than the gene sets established in the literature, hinting that the gene sets
selected by the GA may warrant further analysis in investigating more details
about how E. coli fight against antibiotics. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29949971
TI - Strand-seq enables reliable separation of long reads by chromosome via
expectation maximization.
AB - Motivation: Current sequencing technologies are able to produce reads orders of
magnitude longer than ever possible before. Such long reads have sparked a new
interest in de novo genome assembly, which removes reference biases inherent to
re-sequencing approaches and allows for a direct characterization of complex
genomic variants. However, even with latest algorithmic advances, assembling a
mammalian genome from long error-prone reads incurs a significant computational
burden and does not preclude occasional misassemblies. Both problems could
potentially be mitigated if assembly could commence for each chromosome
separately. Results: To address this, we show how single-cell template strand
sequencing (Strand-seq) data can be leveraged for this purpose. We introduce a
novel latent variable model and a corresponding Expectation Maximization
algorithm, termed SaaRclust, and demonstrates its ability to reliably cluster
long reads by chromosome. For each long read, this approach produces a posterior
probability distribution over all chromosomes of origin and read
directionalities. In this way, it allows to assess the amount of uncertainty
inherent to sparse Strand-seq data on the level of individual reads. Among the
reads that our algorithm confidently assigns to a chromosome, we observed more
than 99% correct assignments on a subset of Pacific Bioscience reads with 30.1*
coverage. To our knowledge, SaaRclust is the first approach for the in silico
separation of long reads by chromosome prior to assembly. Availability and
implementation: https://github.com/daewoooo/SaaRclust.
PMID- 29949973
TI - An optimization framework for network annotation.
AB - Motivation: A chief goal of systems biology is the reconstruction of large-scale
executable models of cellular processes of interest. While accurate continuous
models are still beyond reach, a powerful alternative is to learn a logical model
of the processes under study, which predicts the logical state of any node of the
model as a Boolean function of its incoming nodes. Key to learning such models is
the functional annotation of the underlying physical interactions with
activation/repression (sign) effects. Such annotations are pretty common for a
few well-studied biological pathways. Results: Here we present a novel
optimization framework for large-scale sign annotation that employs different
plausible models of signaling and combines them in a rigorous manner. We apply
our framework to two large-scale knockout datasets in yeast and evaluate its
different components as well as the combined model to predict signs of different
subsets of physical interactions. Overall, we obtain an accurate predictor that
outperforms previous work by a considerable margin. Availability and
implementation: The code is publicly available at
https://github.com/spatkar94/NetworkAnnotation.git.
PMID- 29949972
TI - Association mapping in biomedical time series via statistically significant
shapelet mining.
AB - Motivation: Most modern intensive care units record the physiological and vital
signs of patients. These data can be used to extract signatures, commonly known
as biomarkers, that help physicians understand the biological complexity of many
syndromes. However, most biological biomarkers suffer from either poor predictive
performance or weak explanatory power. Recent developments in time series
classification focus on discovering shapelets, i.e. subsequences that are most
predictive in terms of class membership. Shapelets have the advantage of
combining a high predictive performance with an interpretable component-their
shape. Currently, most shapelet discovery methods do not rely on statistical
tests to verify the significance of individual shapelets. Therefore, identifying
associations between the shapelets of physiological biomarkers and patients that
exhibit certain phenotypes of interest enables the discovery and subsequent
ranking of physiological signatures that are interpretable, statistically
validated and accurate predictors of clinical endpoints. Results: We present a
novel and scalable method for scanning time series and identifying discriminative
patterns that are statistically significant. The significance of a shapelet is
evaluated while considering the problem of multiple hypothesis testing and
mitigating it by efficiently pruning untestable shapelet candidates with Tarone's
method. We demonstrate the utility of our method by discovering patterns in three
of a patient's vital signs: heart rate, respiratory rate and systolic blood
pressure that are indicators of the severity of a future sepsis event, i.e. an
inflammatory response to an infective agent that can lead to organ failure and
death, if not treated in time. Availability and implementation: We make our
method and the scripts that are required to reproduce the experiments publicly
available at https://github.com/BorgwardtLab/S3M. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29949974
TI - Dissecting newly transcribed and old RNA using GRAND-SLAM.
AB - Summary: Global quantification of total RNA is used to investigate steady state
levels of gene expression. However, being able to differentiate pre-existing RNA
(that has been synthesized prior to a defined point in time) and newly
transcribed RNA can provide invaluable information e.g. to estimate RNA half
lives or identify fast and complex regulatory processes. Recently, new techniques
based on metabolic labeling and RNA-seq have emerged that allow to quantify new
and old RNA: Nucleoside analogs are incorporated into newly transcribed RNA and
are made detectable as point mutations in mapped reads. However, relatively
infrequent incorporation events and significant sequencing error rates make the
differentiation between old and new RNA a highly challenging task. We developed a
statistical approach termed GRAND-SLAM that, for the first time, allows to
estimate the proportion of old and new RNA in such an experiment. Uncertainty in
the estimates is quantified in a Bayesian framework. Simulation experiments show
our approach to be unbiased and highly accurate. Furthermore, we analyze how
uncertainty in the proportion translates into uncertainty in estimating RNA half
lives and give guidelines for planning experiments. Finally, we demonstrate that
our estimates of RNA half-lives compare favorably to other experimental
approaches and that biological processes affecting RNA half-lives can be
investigated with greater power than offered by any other method. GRAND-SLAM is
freely available for non-commercial use at http://software.erhard-lab.de; R
scripts to generate all figures are available at zenodo (doi:
10.5281/zenodo.1162340).
PMID- 29949975
TI - Learning with multiple pairwise kernels for drug bioactivity prediction.
AB - Motivation: Many inference problems in bioinformatics, including drug bioactivity
prediction, can be formulated as pairwise learning problems, in which one is
interested in making predictions for pairs of objects, e.g. drugs and their
targets. Kernel-based approaches have emerged as powerful tools for solving
problems of that kind, and especially multiple kernel learning (MKL) offers
promising benefits as it enables integrating various types of complex biomedical
information sources in the form of kernels, along with learning their importance
for the prediction task. However, the immense size of pairwise kernel spaces
remains a major bottleneck, making the existing MKL algorithms computationally
infeasible even for small number of input pairs. Results: We introduce
pairwiseMKL, the first method for time- and memory-efficient learning with
multiple pairwise kernels. pairwiseMKL first determines the mixture weights of
the input pairwise kernels, and then learns the pairwise prediction function.
Both steps are performed efficiently without explicit computation of the massive
pairwise matrices, therefore making the method applicable to solving large
pairwise learning problems. We demonstrate the performance of pairwiseMKL in two
related tasks of quantitative drug bioactivity prediction using up to 167 995
bioactivity measurements and 3120 pairwise kernels: (i) prediction of anticancer
efficacy of drug compounds across a large panel of cancer cell lines; and (ii)
prediction of target profiles of anticancer compounds across their kinome-wide
target spaces. We show that pairwiseMKL provides accurate predictions using
sparse solutions in terms of selected kernels, and therefore it automatically
identifies also data sources relevant for the prediction problem. Availability
and implementation: Code is available at https://github.com/aalto-ics-kepaco.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29949976
TI - Viral quasispecies reconstruction via tensor factorization with successive read
removal.
AB - Motivation: As RNA viruses mutate and adapt to environmental changes, often
developing resistance to anti-viral vaccines and drugs, they form an ensemble of
viral strains--a viral quasispecies. While high-throughput sequencing (HTS) has
enabled in-depth studies of viral quasispecies, sequencing errors and limited
read lengths render the problem of reconstructing the strains and estimating
their spectrum challenging. Inference of viral quasispecies is difficult due to
generally non-uniform frequencies of the strains, and is further exacerbated when
the genetic distances between the strains are small. Results: This paper presents
TenSQR, an algorithm that utilizes tensor factorization framework to analyze HTS
data and reconstruct viral quasispecies characterized by highly uneven
frequencies of its components. Fundamentally, TenSQR performs clustering with
successive data removal to infer strains in a quasispecies in order from the most
to the least abundant one; every time a strain is inferred, sequencing reads
generated from that strain are removed from the dataset. The proposed successive
strain reconstruction and data removal enables discovery of rare strains in a
population and facilitates detection of deletions in such strains. Results on
simulated datasets demonstrate that TenSQR can reconstruct full-length strains
having widely different abundances, generally outperforming state-of-the-art
methods at diversities 1-10% and detecting long deletions even in rare strains. A
study on a real HIV-1 dataset demonstrates that TenSQR outperforms competing
methods in experimental settings as well. Finally, we apply TenSQR to analyze a
Zika virus sample and reconstruct the full-length strains it contains.
Availability and implementation: TenSQR is available at
https://github.com/SoYeonA/TenSQR. Supplementary information: Supplementary data
are available at Bioinformatics online.
PMID- 29949978
TI - Convolutional neural networks for classification of alignments of non-coding RNA
sequences.
AB - Motivation: The convolutional neural network (CNN) has been applied to the
classification problem of DNA sequences, with the additional purpose of motif
discovery. The training of CNNs with distributed representations of four
nucleotides has successfully derived position weight matrices on the learned
kernels that corresponded to sequence motifs such as protein-binding sites.
Results: We propose a novel application of CNNs to classification of pairwise
alignments of sequences for accurate clustering of sequences and show the
benefits of the CNN method of inputting pairwise alignments for clustering of non
coding RNA (ncRNA) sequences and for motif discovery. Classification of a
pairwise alignment of two sequences into positive and negative classes
corresponds to the clustering of the input sequences. After we combined the
distributed representation of RNA nucleotides with the secondary-structure
information specific to ncRNAs and furthermore with mapping profiles of next
generation sequence reads, the training of CNNs for classification of alignments
of RNA sequences yielded accurate clustering in terms of ncRNA families and
outperformed the existing clustering methods for ncRNA sequences. Several
interesting sequence motifs and secondary-structure motifs known for the snoRNA
family and specific to microRNA and tRNA families were identified. Availability
and implementation: The source code of our CNN software in the deep-learning
framework Chainer is available at http://www.dna.bio.keio.ac.jp/cnn/, and the
dataset used for performance evaluation in this work is available at the same
URL.
PMID- 29949977
TI - An integration of fast alignment and maximum-likelihood methods for electron
subtomogram averaging and classification.
AB - Motivation: Cellular Electron CryoTomography (CECT) is an emerging 3D imaging
technique that visualizes subcellular organization of single cells at sub
molecular resolution and in near-native state. CECT captures large numbers of
macromolecular complexes of highly diverse structures and abundances. However,
the structural complexity and imaging limits complicate the systematic de novo
structural recovery and recognition of these macromolecular complexes. Efficient
and accurate reference-free subtomogram averaging and classification represent
the most critical tasks for such analysis. Existing subtomogram alignment based
methods are prone to the missing wedge effects and low signal-to-noise ratio
(SNR). Moreover, existing maximum-likelihood based methods rely on integration
operations, which are in principle computationally infeasible for accurate
calculation. Results: Built on existing works, we propose an integrated method,
Fast Alignment Maximum Likelihood method (FAML), which uses fast subtomogram
alignment to sample sub-optimal rigid transformations. The transformations are
then used to approximate integrals for maximum-likelihood update of subtomogram
averages through expectation-maximization algorithm. Our tests on simulated and
experimental subtomograms showed that, compared to our previously developed fast
alignment method (FA), FAML is significantly more robust to noise and missing
wedge effects with moderate increases of computation cost. Besides, FAML performs
well with significantly fewer input subtomograms when the FA method fails.
Therefore, FAML can serve as a key component for improved construction of initial
structural models from macromolecules captured by CECT. Availability and
implementation: http://www.cs.cmu.edu/mxu1.
PMID- 29949979
TI - Classifying tumors by supervised network propagation.
AB - Motivation: Network propagation has been widely used to aggregate and amplify the
effects of tumor mutations using knowledge of molecular interaction networks.
However, propagating mutations through interactions irrelevant to cancer leads to
erosion of pathway signals and complicates the identification of cancer subtypes.
Results: To address this problem we introduce a propagation algorithm, Network
Based Supervised Stratification (NBS2), which learns the mutated subnetworks
underlying tumor subtypes using a supervised approach. Given an annotated
molecular network and reference tumor mutation profiles for which subtypes have
been predefined, NBS2 is trained by adjusting the weights on interaction features
such that network propagation best recovers the provided subtypes. After
training, weights are fixed such that mutation profiles of new tumors can be
accurately classified. We evaluate NBS2 on breast and glioblastoma tumors,
demonstrating that it outperforms the best network-based approaches in
classifying tumors to known subtypes for these diseases. By interpreting the
interaction weights, we highlight characteristic molecular pathways driving
selected subtypes. Availability and implementation: The NBS2 package is freely
available at: https://github.com/wzhang1984/NBSS. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29949980
TI - Protein threading using residue co-variation and deep learning.
AB - Motivation: Template-based modeling, including homology modeling and protein
threading, is a popular method for protein 3D structure prediction. However,
alignment generation and template selection for protein sequences without close
templates remain very challenging. Results: We present a new method called
DeepThreader to improve protein threading, including both alignment generation
and template selection, by making use of deep learning (DL) and residue co
variation information. Our method first employs DL to predict inter-residue
distance distribution from residue co-variation and sequential information (e.g.
sequence profile and predicted secondary structure), and then builds sequence
template alignment by integrating predicted distance information and sequential
features through an ADMM algorithm. Experimental results suggest that predicted
inter-residue distance is helpful to both protein alignment and template
selection especially for protein sequences without very close templates, and that
our method outperforms currently popular homology modeling method HHpred and
threading method CNFpred by a large margin and greatly outperforms the latest
contact-assisted protein threading method EigenTHREADER. Availability and
implementation: http://raptorx.uchicago.edu/. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29949981
TI - Covariate-dependent negative binomial factor analysis of RNA sequencing data.
AB - Motivation: High-throughput sequencing technologies, in particular RNA sequencing
(RNA-seq), have become the basic practice for genomic studies in biomedical
research. In addition to studying genes individually, for example, through
differential expression analysis, investigating co-ordinated expression
variations of genes may help reveal the underlying cellular mechanisms to derive
better understanding and more effective prognosis and intervention strategies.
Although there exists a variety of co-expression network based methods to analyze
microarray data for this purpose, instead of blindly extending these methods for
microarray data that may introduce unnecessary bias, it is crucial to develop
methods well adapted to RNA-seq data to identify the functional modules of genes
with similar expression patterns. Results: We have developed a fully Bayesian
covariate-dependent negative binomial factor analysis (dNBFA) method-dNBFA-for
RNA-seq count data, to capture coordinated gene expression changes, while
considering effects from covariates reflecting different influencing factors.
Unlike existing co-expression network based methods, our proposed model does not
require multiple ad-hoc choices on data processing, transformation, as well as co
expression measures and can be directly applied to RNA-seq data. Furthermore,
being capable of incorporating covariate information, the proposed method can
tackle setups with complex confounding factors in different experiment designs.
Finally, the natural model parameterization removes the need for a normalization
preprocessing step, as commonly adopted to compensate for the effect of
sequencing-depth variations. Efficient Bayesian inference of model parameters is
derived by exploiting conditional conjugacy via novel data augmentation
techniques. Experimental results on several real-world RNA-seq datasets on
complex diseases suggest dNBFA as a powerful tool for discovering the gene
modules with significant differential expression and meaningful biological
insight. Availability and implementation: dNBFA is implemented in R language and
is available at https://github.com/siamakz/dNBFA.
PMID- 29949982
TI - A space and time-efficient index for the compacted colored de Bruijn graph.
AB - Motivation: Indexing reference sequences for search-both individual genomes and
collections of genomes-is an important building block for many sequence analysis
tasks. Much work has been dedicated to developing full-text indices for genomic
sequences, based on data structures such as the suffix array, the BWT and the FM
index. However, the de Bruijn graph, commonly used for sequence assembly, has
recently been gaining attention as an indexing data structure, due to its natural
ability to represent multiple references using a graphical structure, and to
collapse highly-repetitive sequence regions. Yet, much less attention has been
given as to how to best index such a structure, such that queries can be
performed efficiently and memory usage remains practical as the size and number
of reference sequences being indexed grows large. Results: We present a novel
data structure for representing and indexing the compacted colored de Bruijn
graph, which allows for efficient pattern matching and retrieval of the reference
information associated with each k-mer. As the popularity of the de Bruijn graph
as an index has increased over the past few years, so have the number of proposed
representations of this structure. Existing structures typically fall into two
categories; those that are hashing-based and provide very fast access to the
underlying k-mer information, and those that are space-frugal and provide
asymptotically efficient but practically slower pattern search. Our
representation achieves a compromise between these two extremes. By building upon
minimum perfect hashing and making use of succinct representations where
applicable, our data structure provides practically fast lookup while greatly
reducing the space compared to traditional hashing-based implementations.
Further, we describe a sampling scheme for this index, which provides the ability
to trade off query speed for a reduction in the index size. We believe this
representation strikes a desirable balance between speed and space usage, and
allows for fast search on large reference sequences. Finally, we describe an
application of this index to the taxonomic read assignment problem. We show that
by adopting, essentially, the approach of Kraken, but replacing k-mer presence
with coverage by chains of consistent unique maximal matches, we can improve the
space, speed and accuracy of taxonomic read assignment. Availability and
implementation: pufferfish is written in C++11, is open source, and is available
at https://github.com/COMBINE-lab/pufferfish. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29949983
TI - Bayesian parameter estimation for biochemical reaction networks using region
based adaptive parallel tempering.
AB - Motivation: Mathematical models have become standard tools for the investigation
of cellular processes and the unraveling of signal processing mechanisms. The
parameters of these models are usually derived from the available data using
optimization and sampling methods. However, the efficiency of these methods is
limited by the properties of the mathematical model, e.g. non-identifiabilities,
and the resulting posterior distribution. In particular, multi-modal
distributions with long valleys or pronounced tails are difficult to optimize and
sample. Thus, the developement or improvement of optimization and sampling
methods is subject to ongoing research. Results: We suggest a region-based
adaptive parallel tempering algorithm which adapts to the problem-specific
posterior distributions, i.e. modes and valleys. The algorithm combines several
established algorithms to overcome their individual shortcomings and to improve
sampling efficiency. We assessed its properties for established benchmark
problems and two ordinary differential equation models of biochemical reaction
networks. The proposed algorithm outperformed state-of-the-art methods in terms
of calculation efficiency and mixing. Since the algorithm does not rely on a
specific problem structure, but adapts to the posterior distribution, it is
suitable for a variety of model classes. Availability and implementation: The
code is available both as Supplementary Material and in a Git repository written
in MATLAB. Supplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 29949984
TI - Improving genomics-based predictions for precision medicine through active
elicitation of expert knowledge.
AB - Motivation: Precision medicine requires the ability to predict the efficacies of
different treatments for a given individual using high-dimensional genomic
measurements. However, identifying predictive features remains a challenge when
the sample size is small. Incorporating expert knowledge offers a promising
approach to improve predictions, but collecting such knowledge is laborious if
the number of candidate features is very large. Results: We introduce a
probabilistic framework to incorporate expert feedback about the impact of
genomic measurements on the outcome of interest and present a novel approach to
collect the feedback efficiently, based on Bayesian experimental design. The new
approach outperformed other recent alternatives in two medical applications:
prediction of metabolic traits and prediction of sensitivity of cancer cells to
different drugs, both using genomic features as predictors. Furthermore, the
intelligent approach to collect feedback reduced the workload of the expert to
approximately 11%, compared to a baseline approach. Availability and
implementation: Source code implementing the introduced computational methods is
freely available at https://github.com/AaltoPML/knowledge-elicitation-for
precision-medicine. Supplementary information: Supplementary data are available
at Bioinformatics online.
PMID- 29949985
TI - Enumerating consistent sub-graphs of directed acyclic graphs: an insight into
biomedical ontologies.
AB - Motivation: Modern problems of concept annotation associate an object of interest
(gene, individual, text document) with a set of interrelated textual descriptors
(functions, diseases, topics), often organized in concept hierarchies or
ontologies. Most ontology can be seen as directed acyclic graphs (DAGs), where
nodes represent concepts and edges represent relational ties between these
concepts. Given an ontology graph, each object can only be annotated by a
consistent sub-graph; that is, a sub-graph such that if an object is annotated by
a particular concept, it must also be annotated by all other concepts that
generalize it. Ontologies therefore provide a compact representation of a large
space of possible consistent sub-graphs; however, until now we have not been
aware of a practical algorithm that can enumerate such annotation spaces for a
given ontology. Results: We propose an algorithm for enumerating consistent sub
graphs of DAGs. The algorithm recursively partitions the graph into strictly
smaller graphs until the resulting graph becomes a rooted tree (forest), for
which a linear-time solution is computed. It then combines the tallies from
graphs created in the recursion to obtain the final count. We prove the
correctness of this algorithm, propose several practical accelerations, evaluate
it on random graphs and then apply it to characterize four major biomedical
ontologies. We believe this work provides valuable insights into the complexity
of concept annotation spaces and its potential influence on the predictability of
ontological annotation. Availability and implementation: https://github.com/shawn
peng/counting-consistent-sub-DAG. Supplementary information: Supplementary data
are available at Bioinformatics online.
PMID- 29949986
TI - Predicting CTCF-mediated chromatin loops using CTCF-MP.
AB - Motivation: The three dimensional organization of chromosomes within the cell
nucleus is highly regulated. It is known that CCCTC-binding factor (CTCF) is an
important architectural protein to mediate long-range chromatin loops. Recent
studies have shown that the majority of CTCF binding motif pairs at chromatin
loop anchor regions are in convergent orientation. However, it remains unknown
whether the genomic context at the sequence level can determine if a convergent
CTCF motif pair is able to form a chromatin loop. Results: In this article, we
directly ask whether and what sequence-based features (other than the motif
itself) may be important to establish CTCF-mediated chromatin loops. We found
that motif conservation measured by 'branch-of-origin' that accounts for motif
turn-over in evolution is an important feature. We developed a new machine
learning algorithm called CTCF-MP based on word2vec to demonstrate that sequence
based features alone have the capability to predict if a pair of convergent CTCF
motifs would form a loop. Together with functional genomic signals from CTCF ChIP
seq and DNase-seq, CTCF-MP is able to make highly accurate predictions on whether
a convergent CTCF motif pair would form a loop in a single cell type and also
across different cell types. Our work represents an important step further to
understand the sequence determinants that may guide the formation of complex
chromatin architectures. Availability and implementation: The source code of CTCF
MP can be accessed at: https://github.com/ma-compbio/CTCF-MP. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29949987
TI - mGPfusion: predicting protein stability changes with Gaussian process kernel
learning and data fusion.
AB - Motivation: Proteins are commonly used by biochemical industry for numerous
processes. Refining these proteins' properties via mutations causes stability
effects as well. Accurate computational method to predict how mutations affect
protein stability is necessary to facilitate efficient protein design. However,
accuracy of predictive models is ultimately constrained by the limited
availability of experimental data. Results: We have developed mGPfusion, a novel
Gaussian process (GP) method for predicting protein's stability changes upon
single and multiple mutations. This method complements the limited experimental
data with large amounts of molecular simulation data. We introduce a Bayesian
data fusion model that re-calibrates the experimental and in silico data sources
and then learns a predictive GP model from the combined data. Our protein
specific model requires experimental data only regarding the protein of interest
and performs well even with few experimental measurements. The mGPfusion models
proteins by contact maps and infers the stability effects caused by mutations
with a mixture of graph kernels. Our results show that mGPfusion outperforms
state-of-the-art methods in predicting protein stability on a dataset of 15
different proteins and that incorporating molecular simulation data improves the
model learning and prediction accuracy. Availability and implementation: Software
implementation and datasets are available at github.com/emmijokinen/mgpfusion.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29949988
TI - Scalable preprocessing for sparse scRNA-seq data exploiting prior knowledge.
AB - Motivation: Single cell RNA-seq (scRNA-seq) data contains a wealth of information
which has to be inferred computationally from the observed sequencing reads. As
the ability to sequence more cells improves rapidly, existing computational tools
suffer from three problems. (i) The decreased reads-per-cell implies a highly
sparse sample of the true cellular transcriptome. (ii) Many tools simply cannot
handle the size of the resulting datasets. (iii) Prior biological knowledge such
as bulk RNA-seq information of certain cell types or qualitative marker
information is not taken into account. Here we present UNCURL, a preprocessing
framework based on non-negative matrix factorization for scRNA-seq data, that is
able to handle varying sampling distributions, scales to very large cell numbers
and can incorporate prior knowledge. Results: We find that preprocessing using
UNCURL consistently improves performance of commonly used scRNA-seq tools for
clustering, visualization and lineage estimation, both in the absence and
presence of prior knowledge. Finally we demonstrate that UNCURL is extremely
scalable and parallelizable, and runs faster than other methods on a scRNA-seq
dataset containing 1.3 million cells. Availability and implementation: Source
code is available at https://github.com/yjzhang/uncurl_python. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29949989
TI - A graph-based approach to diploid genome assembly.
AB - Motivation: Constructing high-quality haplotype-resolved de novo assemblies of
diploid genomes is important for revealing the full extent of structural
variation and its role in health and disease. Current assembly approaches often
collapse the two sequences into one haploid consensus sequence and, therefore,
fail to capture the diploid nature of the organism under study. Thus, building an
assembler capable of producing accurate and complete diploid assemblies, while
being resource-efficient with respect to sequencing costs, is a key challenge to
be addressed by the bioinformatics community. Results: We present a novel graph
based approach to diploid assembly, which combines accurate Illumina data and
long-read Pacific Biosciences (PacBio) data. We demonstrate the effectiveness of
our method on a pseudo-diploid yeast genome and show that we require as little as
50* coverage Illumina data and 10* PacBio data to generate accurate and complete
assemblies. Additionally, we show that our approach has the ability to detect and
phase structural variants. Availability and implementation:
https://github.com/whatshap/whatshap. Supplementary information: Supplementary
data are available at Bioinformatics online.
PMID- 29949990
TI - Optimization and profile calculation of ODE models using second order adjoint
sensitivity analysis.
AB - Motivation: Parameter estimation methods for ordinary differential equation (ODE)
models of biological processes can exploit gradients and Hessians of objective
functions to achieve convergence and computational efficiency. However, the
computational complexity of established methods to evaluate the Hessian scales
linearly with the number of state variables and quadratically with the number of
parameters. This limits their application to low-dimensional problems. Results:
We introduce second order adjoint sensitivity analysis for the computation of
Hessians and a hybrid optimization-integration-based approach for profile
likelihood computation. Second order adjoint sensitivity analysis scales linearly
with the number of parameters and state variables. The Hessians are effectively
exploited by the proposed profile likelihood computation approach. We evaluate
our approaches on published biological models with real measurement data. Our
study reveals an improved computational efficiency and robustness of optimization
compared to established approaches, when using Hessians computed with adjoint
sensitivity analysis. The hybrid computation method was more than 2-fold faster
than the best competitor. Thus, the proposed methods and implemented algorithms
allow for the improvement of parameter estimation for medium and large scale ODE
models. Availability and implementation: The algorithms for second order adjoint
sensitivity analysis are implemented in the Advanced MATLAB Interface to CVODES
and IDAS (AMICI, https://github.com/ICB-DCM/AMICI/). The algorithm for hybrid
profile likelihood computation is implemented in the parameter estimation toolbox
(PESTO, https://github.com/ICB-DCM/PESTO/). Both toolboxes are freely available
under the BSD license. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29949991
TI - Finding associated variants in genome-wide association studies on multiple
traits.
AB - Motivation: Many variants identified by genome-wide association studies (GWAS)
have been found to affect multiple traits, either directly or through shared
pathways. There is currently a wealth of GWAS data collected in numerous
phenotypes, and analyzing multiple traits at once can increase power to detect
shared variant effects. However, traditional meta-analysis methods are not
suitable for combining studies on different traits. When applied to dissimilar
studies, these meta-analysis methods can be underpowered compared to univariate
analysis. The degree to which traits share variant effects is often not known,
and the vast majority of GWAS meta-analysis only consider one trait at a time.
Results: Here, we present a flexible method for finding associated variants from
GWAS summary statistics for multiple traits. Our method estimates the degree of
shared effects between traits from the data. Using simulations, we show that our
method properly controls the false positive rate and increases power when an
effect is present in a subset of traits. We then apply our method to the North
Finland Birth Cohort and UK Biobank datasets using a variety of metabolic traits
and discover novel loci. Availability and implementation: Our source code is
available at https://github.com/lgai/CONFIT. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29949992
TI - AnoniMME: bringing anonymity to the Matchmaker Exchange platform for rare disease
gene discovery.
AB - Summary: Advances in genome sequencing and genomics research are bringing us
closer to a new era of personalized medicine, where healthcare can be tailored to
the individual's genetic makeup and to more effective diagnosis and treatment of
rare genetic diseases. Much of this progress depends on collaborations and access
to data, thus, a number of initiatives have been introduced to support seamless
data sharing. Among these, the Global Alliance for Genomics and Health has
developed and operates a platform, called Matchmaker Exchange (MME), which allows
researchers to perform queries for rare genetic disease discovery over multiple
federated databases. Queries include gene variations which are linked to rare
diseases, and the ability to find other researchers that have seen or have
interest in those variations is extremely valuable. Nonetheless, in some cases,
researchers may be reluctant to use the platform since the queries they make
(thus, what they are working on) are revealed to other researchers, and this
creates concerns with respect to privacy and competitive advantage. In this
paper, we present AnoniMME, a framework geared to enable anonymous queries within
the MME platform. The framework, building on a cryptographic primitive called
Reverse Private Information Retrieval, let researchers anonymously query the
federated platform, in a multi-server setting-specifically, they write their
query, along with a public encryption key, anonymously in a public database.
Responses are also supported, so that other researchers can respond to queries by
providing their encrypted contact details. Availability and implementation:
https://github.com/bristena-op/AnoniMME.
PMID- 29949993
TI - Discriminating early- and late-stage cancers using multiple kernel learning on
gene sets.
AB - Motivation: Identifying molecular mechanisms that drive cancers from early to
late stages is highly important to develop new preventive and therapeutic
strategies. Standard machine learning algorithms could be used to discriminate
early- and late-stage cancers from each other using their genomic
characterizations. Even though these algorithms would get satisfactory predictive
performance, their knowledge extraction capability would be quite restricted due
to highly correlated nature of genomic data. That is why we need algorithms that
can also extract relevant information about these biological mechanisms using our
prior knowledge about pathways/gene sets. Results: In this study, we addressed
the problem of separating early- and late-stage cancers from each other using
their gene expression profiles. We proposed to use a multiple kernel learning
(MKL) formulation that makes use of pathways/gene sets (i) to obtain
satisfactory/improved predictive performance and (ii) to identify biological
mechanisms that might have an effect in cancer progression. We extensively
compared our proposed MKL on gene sets algorithm against two standard machine
learning algorithms, namely, random forests and support vector machines, on 20
diseases from the Cancer Genome Atlas cohorts for two different sets of
experiments. Our method obtained statistically significantly better or comparable
predictive performance on most of the datasets using significantly fewer gene
expression features. We also showed that our algorithm was able to extract
meaningful and disease-specific information that gives clues about the
progression mechanism. Availability and implementation: Our implementations of
support vector machine and multiple kernel learning algorithms in R are available
at https://github.com/mehmetgonen/gsbc together with the scripts that replicate
the reported experiments.
PMID- 29949994
TI - A new method for constructing tumor specific gene co-expression networks based on
samples with tumor purity heterogeneity.
AB - Motivation: Tumor tissue samples often contain an unknown fraction of stromal
cells. This problem is widely known as tumor purity heterogeneity (TPH) was
recently recognized as a severe issue in omics studies. Specifically, if TPH is
ignored when inferring co-expression networks, edges are likely to be estimated
among genes with mean shift between non-tumor- and tumor cells rather than among
gene pairs interacting with each other in tumor cells. To address this issue, we
propose Tumor Specific Net (TSNet), a new method which constructs tumor-cell
specific gene/protein co-expression networks based on gene/protein expression
profiles of tumor tissues. TSNet treats the observed expression profile as a
mixture of expressions from different cell types and explicitly models tumor
purity percentage in each tumor sample. Results: Using extensive synthetic data
experiments, we demonstrate that TSNet outperforms a standard graphical model
which does not account for TPH. We then apply TSNet to estimate tumor specific
gene co-expression networks based on TCGA ovarian cancer RNAseq data. We identify
novel co-expression modules and hub structure specific to tumor cells.
Availability and implementation: R codes can be found at
https://github.com/petraf01/TSNet. Supplementary information: Supplementary data
are available at Bioinformatics online.
PMID- 29949995
TI - Asymptotically optimal minimizers schemes.
AB - Motivation: The minimizers technique is a method to sample k-mers that is used in
many bioinformatics software to reduce computation, memory usage and run time.
The number of applications using minimizers keeps on growing steadily. Despite
its many uses, the theoretical understanding of minimizers is still very limited.
In many applications, selecting as few k-mers as possible (i.e. having a low
density) is beneficial. The density is highly dependent on the choice of the
order on the k-mers. Different applications use different orders, but none of
these orders are optimal. A better understanding of minimizers schemes, and the
related local and forward schemes, will allow designing schemes with lower
density and thereby making existing and future bioinformatics tools even more
efficient. Results: From the analysis of the asymptotic behavior of minimizers,
forward and local schemes, we show that the previously believed lower bound on
minimizers schemes does not hold, and that schemes with density lower than
thought possible actually exist. The proof is constructive and leads to an
efficient algorithm to compare k-mers. These orders are the first known orders
that are asymptotically optimal. Additionally, we give improved bounds on the
density achievable by the three type of schemes.
PMID- 29949996
TI - Modeling polypharmacy side effects with graph convolutional networks.
AB - Motivation: The use of drug combinations, termed polypharmacy, is common to treat
patients with complex diseases or co-existing conditions. However, a major
consequence of polypharmacy is a much higher risk of adverse side effects for the
patient. Polypharmacy side effects emerge because of drug-drug interactions, in
which activity of one drug may change, favorably or unfavorably, if taken with
another drug. The knowledge of drug interactions is often limited because these
complex relationships are rare, and are usually not observed in relatively small
clinical testing. Discovering polypharmacy side effects thus remains an important
challenge with significant implications for patient mortality and morbidity.
Results: Here, we present Decagon, an approach for modeling polypharmacy side
effects. The approach constructs a multimodal graph of protein-protein
interactions, drug-protein target interactions and the polypharmacy side effects,
which are represented as drug-drug interactions, where each side effect is an
edge of a different type. Decagon is developed specifically to handle such
multimodal graphs with a large number of edge types. Our approach develops a new
graph convolutional neural network for multirelational link prediction in
multimodal networks. Unlike approaches limited to predicting simple drug-drug
interaction values, Decagon can predict the exact side effect, if any, through
which a given drug combination manifests clinically. Decagon accurately predicts
polypharmacy side effects, outperforming baselines by up to 69%. We find that it
automatically learns representations of side effects indicative of co-occurrence
of polypharmacy in patients. Furthermore, Decagon models particularly well
polypharmacy side effects that have a strong molecular basis, while on
predominantly non-molecular side effects, it achieves good performance because of
effective sharing of model parameters across edge types. Decagon opens up
opportunities to use large pharmacogenomic and patient population data to flag
and prioritize polypharmacy side effects for follow-up analysis via formal
pharmacological studies. Availability and implementation: Source code and
preprocessed datasets are at: http://snap.stanford.edu/decagon.
PMID- 29949997
TI - Personalized regression enables sample-specific pan-cancer analysis.
AB - Motivation: In many applications, inter-sample heterogeneity is crucial to
understanding the complex biological processes under study. For example, in
genomic analysis of cancers, each patient in a cohort may have a different driver
mutation, making it difficult or impossible to identify causal mutations from an
averaged view of the entire cohort. Unfortunately, many traditional methods for
genomic analysis seek to estimate a single model which is shared by all samples
in a population, ignoring this inter-sample heterogeneity entirely. In order to
better understand patient heterogeneity, it is necessary to develop practical,
personalized statistical models. Results: To uncover this inter-sample
heterogeneity, we propose a novel regularizer for achieving patient-specific
personalized estimation. This regularizer operates by learning two latent
distance metrics-one between personalized parameters and one between clinical
covariates-and attempting to match the induced distances as closely as possible.
Crucially, we do not assume these distance metrics are already known. Instead, we
allow the data to dictate the structure of these latent distance metrics.
Finally, we apply our method to learn patient-specific, interpretable models for
a pan-cancer gene expression dataset containing samples from more than 30
distinct cancer types and find strong evidence of personalization effects between
cancer types as well as between individuals. Our analysis uncovers sample
specific aberrations that are overlooked by population-level methods, suggesting
a promising new path for precision analysis of complex diseases such as cancer.
Availability and implementation: Software for personalized linear and
personalized logistic regression, along with code to reproduce experimental
results, is freely available at github.com/blengerich/personalized_regression.
PMID- 29949998
TI - NeuroMorphoVis: a collaborative framework for analysis and visualization of
neuronal morphology skeletons reconstructed from microscopy stacks.
AB - Motivation: From image stacks to computational models, processing digital
representations of neuronal morphologies is essential to neuroscientific
research. Workflows involve various techniques and tools, leading in certain
cases to convoluted and fragmented pipelines. The existence of an integrated,
extensible and free framework for processing, analysis and visualization of those
morphologies is a challenge that is still largely unfulfilled. Results: We
present NeuroMorphoVis, an interactive, extensible and cross-platform framework
for building, visualizing and analyzing digital reconstructions of neuronal
morphology skeletons extracted from microscopy stacks. Our framework is capable
of detecting and repairing tracing artifacts, allowing the generation of high
fidelity surface meshes and high resolution volumetric models for simulation and
in silico imaging studies. The applicability of NeuroMorphoVis is demonstrated
with two case studies. The first simulates the construction of three-dimensional
profiles of neuronal somata and the other highlights how the framework is
leveraged to create volumetric models of neuronal circuits for simulating
different types of in vitro imaging experiments. Availability and implementation:
The source code and documentation are freely available on
https://github.com/BlueBrain/NeuroMorphoVis under the GNU public license. The
morphological analysis, visualization and surface meshing are implemented as an
extensible Python API (Application Programming Interface) based on Blender, and
the volume reconstruction and analysis code is written in C++ and parallelized
using OpenMP. The framework features are accessible from a user-friendly GUI
(Graphical User Interface) and a rich CLI (Command Line Interface). Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29949999
TI - Onto2Vec: joint vector-based representation of biological entities and their
ontology-based annotations.
AB - Motivation: Biological knowledge is widely represented in the form of ontology
based annotations: ontologies describe the phenomena assumed to exist within a
domain, and the annotations associate a (kind of) biological entity with a set of
phenomena within the domain. The structure and information contained in
ontologies and their annotations make them valuable for developing machine
learning, data analysis and knowledge extraction algorithms; notably, semantic
similarity is widely used to identify relations between biological entities, and
ontology-based annotations are frequently used as features in machine learning
applications. Results: We propose the Onto2Vec method, an approach to learn
feature vectors for biological entities based on their annotations to biomedical
ontologies. Our method can be applied to a wide range of bioinformatics research
problems such as similarity-based prediction of interactions between proteins,
classification of interaction types using supervised learning, or clustering. To
evaluate Onto2Vec, we use the gene ontology (GO) and jointly produce dense vector
representations of proteins, the GO classes to which they are annotated, and the
axioms in GO that constrain these classes. First, we demonstrate that Onto2Vec
generated feature vectors can significantly improve prediction of protein-protein
interactions in human and yeast. We then illustrate how Onto2Vec representations
provide the means for constructing data-driven, trainable semantic similarity
measures that can be used to identify particular relations between proteins.
Finally, we use an unsupervised clustering approach to identify protein families
based on their Enzyme Commission numbers. Our results demonstrate that Onto2Vec
can generate high quality feature vectors from biological entities and
ontologies. Onto2Vec has the potential to significantly outperform the state-of
the-art in several predictive applications in which ontologies are involved.
Availability and implementation: https://github.com/bio-ontology-research
group/onto2vec. Supplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 29950000
TI - Improved pathway reconstruction from RNA interference screens by exploiting off
target effects.
AB - Motivation: Pathway reconstruction has proven to be an indispensable tool for
analyzing the molecular mechanisms of signal transduction underlying cell
function. Nested effects models (NEMs) are a class of probabilistic graphical
models designed to reconstruct signalling pathways from high-dimensional
observations resulting from perturbation experiments, such as RNA interference
(RNAi). NEMs assume that the short interfering RNAs (siRNAs) designed to
knockdown specific genes are always on-target. However, it has been shown that
most siRNAs exhibit strong off-target effects, which further confound the data,
resulting in unreliable reconstruction of networks by NEMs. Results: Here, we
present an extension of NEMs called probabilistic combinatorial nested effects
models (pc-NEMs), which capitalize on the ancillary siRNA off-target effects for
network reconstruction from combinatorial gene knockdown data. Our model employs
an adaptive simulated annealing search algorithm for simultaneous inference of
network structure and error rates inherent to the data. Evaluation of pc-NEMs on
simulated data with varying number of phenotypic effects and noise levels as well
as real data demonstrates improved reconstruction compared to classical NEMs.
Application to Bartonella henselae infection RNAi screening data yielded an eight
node network largely in agreement with previous works, and revealed novel binary
interactions of direct impact between established components. Availability and
implementation: The software used for the analysis is freely available as an R
package at https://github.com/cbg-ethz/pcNEM.git. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29950001
TI - Deconvolution and phylogeny inference of structural variations in tumor genomic
samples.
AB - Motivation: Phylogenetic reconstruction of tumor evolution has emerged as a
crucial tool for making sense of the complexity of emerging cancer genomic
datasets. Despite the growing use of phylogenetics in cancer studies, though, the
field has only slowly adapted to many ways that tumor evolution differs from
classic species evolution. One crucial question in that regard is how to handle
inference of structural variations (SVs), which are a major mechanism of
evolution in cancers but have been largely neglected in tumor phylogenetics to
date, in part due to the challenges of reliably detecting and typing SVs and
interpreting them phylogenetically. Results: We present a novel method for
reconstructing evolutionary trajectories of SVs from bulk whole-genome sequence
data via joint deconvolution and phylogenetics, to infer clonal sub-populations
and reconstruct their ancestry. We establish a novel likelihood model for joint
deconvolution and phylogenetic inference on bulk SV data and formulate an
associated optimization algorithm. We demonstrate the approach to be efficient
and accurate for realistic scenarios of SV mutation on simulated data.
Application to breast cancer genomic data from The Cancer Genome Atlas shows it
to be practical and effective at reconstructing features of SV-driven evolution
in single tumors. Availability and implementation: Python source code and
associated documentation are available at https://github.com/jaebird123/tusv.
PMID- 29950002
TI - SigMat: a classification scheme for gene signature matching.
AB - Motivation: Several large-scale efforts have been made to collect gene expression
signatures from a variety of biological conditions, such as response of cell
lines to treatment with drugs, or tumor samples with different characteristics.
These gene signature collections are utilized through bioinformatics tools for
'signature matching', whereby a researcher studying an expression profile can
identify previously cataloged biological conditions most related to their
profile. Signature matching tools typically retrieve from the collection the
signature that has highest similarity to the user-provided profile.
Alternatively, classification models may be applied where each biological
condition in the signature collection is a class label; however, such models are
trained on the collection of available signatures and may not generalize to the
novel cellular context or cell line of the researcher's expression profile.
Results: We present an advanced multi-way classification algorithm for signature
matching, called SigMat, that is trained on a large signature collection from a
well-studied cellular context, but can also classify signatures from other cell
types by relying on an additional, small collection of signatures representing
the target cell type. It uses these 'tuning data' to learn two additional
parameters that help adapt its predictions for other cellular contexts. SigMat
outperforms other similarity scores and classification methods in identifying the
correct label of a query expression profile from as many as 244 or 500 candidate
classes (drug treatments) cataloged by the LINCS L1000 project. SigMat retains
its high accuracy in cross-cell line applications even when the amount of tuning
data is severely limited. Availability and implementation: SigMat is available on
GitHub at https://github.com/JinfengXiao/SigMat. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29950003
TI - Driver gene mutations based clustering of tumors: methods and applications.
AB - Motivation: Somatic mutations in proto-oncogenes and tumor suppressor genes
constitute a major category of causal genetic abnormalities in tumor cells. The
mutation spectra of thousands of tumors have been generated by The Cancer Genome
Atlas (TCGA) and other whole genome (exome) sequencing projects. A promising
approach to utilizing these resources for precision medicine is to identify
genetic similarity-based sub-types within a cancer type and relate the pinpointed
sub-types to the clinical outcomes and pathologic characteristics of patients.
Results: We propose two novel methods, ccpwModel and xGeneModel, for mutation
based clustering of tumors. In the former, binary variables indicating the status
of cancer driver genes in tumors and the genes' involvement in the core cancer
pathways are treated as the features in the clustering process. In the latter,
the functional similarities of putative cancer driver genes and their confidence
scores as the 'true' driver genes are integrated with the mutation spectra to
calculate the genetic distances between tumors. We apply both methods to the TCGA
data of 16 cancer types. Promising results are obtained when these methods are
compared to state-of-the-art approaches as to the associations between the
determined tumor clusters and patient race (or survival time). We further extend
the analysis to detect mutation-characterized transcriptomic prognostic
signatures, which are directly relevant to the etiology of carcinogenesis.
Availability and implementation: R codes and example data for ccpwModel and
xGeneModel can be obtained from
http://webusers.xula.edu/kzhang/ISMB2018/ccpw_xGene_software.zip. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29950004
TI - Inference of species phylogenies from bi-allelic markers using pseudo-likelihood.
AB - Motivation: Phylogenetic networks represent reticulate evolutionary histories.
Statistical methods for their inference under the multispecies coalescent have
recently been developed. A particularly powerful approach uses data that consist
of bi-allelic markers (e.g. single nucleotide polymorphism data) and allows for
exact likelihood computations of phylogenetic networks while numerically
integrating over all possible gene trees per marker. While the approach has good
accuracy in terms of estimating the network and its parameters, likelihood
computations remain a major computational bottleneck and limit the method's
applicability. Results: In this article, we first demonstrate why likelihood
computations of networks take orders of magnitude more time when compared to
trees. We then propose an approach for inference of phylogenetic networks based
on pseudo-likelihood using bi-allelic markers. We demonstrate the scalability and
accuracy of phylogenetic network inference via pseudo-likelihood computations on
simulated data. Furthermore, we demonstrate aspects of robustness of the method
to violations in the underlying assumptions of the employed statistical model.
Finally, we demonstrate the application of the method to biological data. The
proposed method allows for analyzing larger datasets in terms of the numbers of
taxa and reticulation events. While pseudo-likelihood had been proposed before
for data consisting of gene trees, the work here uses sequence data directly,
offering several advantages as we discuss. Availability and implementation: The
methods have been implemented in PhyloNet (http://bioinfocs.rice.edu/phylonet).
PMID- 29950005
TI - Unsupervised embedding of single-cell Hi-C data.
AB - Motivation: Single-cell Hi-C (scHi-C) data promises to enable scientists to
interrogate the 3D architecture of DNA in the nucleus of the cell, studying how
this structure varies stochastically or along developmental or cell-cycle axes.
However, Hi-C data analysis requires methods that take into account the unique
characteristics of this type of data. In this work, we explore whether methods
that have been developed previously for the analysis of bulk Hi-C data can be
applied to scHi-C data. We apply methods designed for analysis of bulk Hi-C data
to scHi-C data in conjunction with unsupervised embedding. Results: We find that
one of these methods, HiCRep, when used in conjunction with multidimensional
scaling (MDS), strongly outperforms three other methods, including a technique
that has been used previously for scHi-C analysis. We also provide evidence that
the HiCRep/MDS method is robust to extremely low per-cell sequencing depth, that
this robustness is improved even further when high-coverage and low-coverage
cells are projected together, and that the method can be used to jointly embed
cells from multiple published datasets.
PMID- 29950006
TI - Random forest based similarity learning for single cell RNA sequencing data.
AB - Motivation: Genome-wide transcriptome sequencing applied to single cells (scRNA
seq) is rapidly becoming an assay of choice across many fields of biological and
biomedical research. Scientific objectives often revolve around discovery or
characterization of types or sub-types of cells, and therefore, obtaining
accurate cell-cell similarities from scRNA-seq data is a critical step in many
studies. While rapid advances are being made in the development of tools for
scRNA-seq data analysis, few approaches exist that explicitly address this task.
Furthermore, abundance and type of noise present in scRNA-seq datasets suggest
that application of generic methods, or of methods developed for bulk RNA-seq
data, is likely suboptimal. Results: Here, we present RAFSIL, a random forest
based approach to learn cell-cell similarities from scRNA-seq data. RAFSIL
implements a two-step procedure, where feature construction geared towards scRNA
seq data is followed by similarity learning. It is designed to be adaptable and
expandable, and RAFSIL similarities can be used for typical exploratory data
analysis tasks like dimension reduction, visualization and clustering. We show
that our approach compares favorably with current methods across a diverse
collection of datasets, and that it can be used to detect and highlight unwanted
technical variation in scRNA-seq datasets in situations where other methods fail.
Overall, RAFSIL implements a flexible approach yielding a useful tool that
improves the analysis of scRNA-seq data. Availability and implementation: The
RAFSIL R package is available at www.kostkalab.net/software.html. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29950007
TI - An evolutionary model motivated by physicochemical properties of amino acids
reveals variation among proteins.
AB - Motivation: The relative rates of amino acid interchanges over evolutionary time
are likely to vary among proteins. Variation in those rates has the potential to
reveal information about constraints on proteins. However, the most
straightforward model that could be used to estimate relative rates of amino acid
substitution is parameter-rich and it is therefore impractical to use for this
purpose. Results: A six-parameter model of amino acid substitution that
incorporates information about the physicochemical properties of amino acids was
developed. It showed that amino acid side chain volume, polarity and aromaticity
have major impacts on protein evolution. It also revealed variation among
proteins in the relative importance of those properties. The same general
approach can be used to improve the fit of empirical models such as the commonly
used PAM and LG models. Availability and implementation: Perl code and test data
are available from https://github.com/ebraun68/sixparam. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29950008
TI - MicroPheno: predicting environments and host phenotypes from 16S rRNA gene
sequencing using a k-mer based representation of shallow sub-samples.
AB - Motivation: Microbial communities play important roles in the function and
maintenance of various biosystems, ranging from the human body to the
environment. A major challenge in microbiome research is the classification of
microbial communities of different environments or host phenotypes. The most
common and cost-effective approach for such studies to date is 16S rRNA gene
sequencing. Recent falls in sequencing costs have increased the demand for
simple, efficient and accurate methods for rapid detection or diagnosis with
proved applications in medicine, agriculture and forensic science. We describe a
reference- and alignment-free approach for predicting environments and host
phenotypes from 16S rRNA gene sequencing based on k-mer representations that
benefits from a bootstrapping framework for investigating the sufficiency of
shallow sub-samples. Deep learning methods as well as classical approaches were
explored for predicting environments and host phenotypes. Results: A k-mer
distribution of shallow sub-samples outperformed Operational Taxonomic Unit (OTU)
features in the tasks of body-site identification and Crohn's disease prediction.
Aside from being more accurate, using k-mer features in shallow sub-samples
allows (i) skipping computationally costly sequence alignments required in OTU
picking and (ii) provided a proof of concept for the sufficiency of shallow and
short-length 16S rRNA sequencing for phenotype prediction. In addition, k-mer
features predicted representative 16S rRNA gene sequences of 18 ecological
environments, and 5 organismal environments with high macro-F1 scores of 0.88 and
0.87. For large datasets, deep learning outperformed classical methods such as
Random Forest and Support Vector Machine. Availability and implementation: The
software and datasets are available at https://llp.berkeley.edu/micropheno.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29950009
TI - SIMPLE: Sparse Interaction Model over Peaks of moLEcules for fast, interpretable
metabolite identification from tandem mass spectra.
AB - Motivation: Recent success in metabolite identification from tandem mass spectra
has been led by machine learning, which has two stages: mapping mass spectra to
molecular fingerprint vectors and then retrieving candidate molecules from the
database. In the first stage, i.e. fingerprint prediction, spectrum peaks are
features and considering their interactions would be reasonable for more accurate
identification of unknown metabolites. Existing approaches of fingerprint
prediction are based on only individual peaks in the spectra, without explicitly
considering the peak interactions. Also the current cutting-edge method is based
on kernels, which are computationally heavy and difficult to interpret. Results:
We propose two learning models that allow to incorporate peak interactions for
fingerprint prediction. First, we extend the state-of-the-art kernel learning
method by developing kernels for peak interactions to combine with kernels for
peaks through multiple kernel learning (MKL). Second, we formulate a sparse
interaction model for metabolite peaks, which we call SIMPLE, which is
computationally light and interpretable for fingerprint prediction. The
formulation of SIMPLE is convex and guarantees global optimization, for which we
develop an alternating direction method of multipliers (ADMM) algorithm.
Experiments using the MassBank dataset show that both models achieved comparative
prediction accuracy with the current top-performance kernel method. Furthermore
SIMPLE clearly revealed individual peaks and peak interactions which contribute
to enhancing the performance of fingerprint prediction. Availability and
implementation: The code will be accessed through
http://mamitsukalab.org/tools/SIMPLE/.
PMID- 29950011
TI - Training for translation between disciplines: a philosophy for life and data
sciences curricula.
AB - Motivation: Our society has become data-rich to the extent that research in many
areas has become impossible without computational approaches. Educational
programmes seem to be lagging behind this development. At the same time, there is
a growing need not only for strong data science skills, but foremost for the
ability to both translate between tools and methods on the one hand, and
application and problems on the other. Results: Here we present our experiences
with shaping and running a masters' programme in bioinformatics and systems
biology in Amsterdam. From this, we have developed a comprehensive philosophy on
how translation in training may be achieved in a dynamic and multidisciplinary
research area, which is described here. We furthermore describe two requirements
that enable translation, which we have found to be crucial: sufficient depth and
focus on multidisciplinary topic areas, coupled with a balanced breadth from
adjacent disciplines. Finally, we present concrete suggestions on how this may be
implemented in practice, which may be relevant for the effectiveness of life
science and data science curricula in general, and of particular interest to
those who are in the process of setting up such curricula. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29950010
TI - GSEA-InContext: identifying novel and common patterns in expression experiments.
AB - Motivation: Gene Set Enrichment Analysis (GSEA) is routinely used to analyze and
interpret coordinate pathway-level changes in transcriptomics experiments. For an
experiment where less than seven samples per condition are compared, GSEA employs
a competitive null hypothesis to test significance. A gene set enrichment score
is tested against a null distribution of enrichment scores generated from
permuted gene sets, where genes are randomly selected from the input experiment.
Looking across a variety of biological conditions, however, genes are not
randomly distributed with many showing consistent patterns of up- or down
regulation. As a result, common patterns of positively and negatively enriched
gene sets are observed across experiments. Placing a single experiment into the
context of a relevant set of background experiments allows us to identify both
the common and experiment-specific patterns of gene set enrichment. Results: We
compiled a compendium of 442 small molecule transcriptomic experiments and used
GSEA to characterize common patterns of positively and negatively enriched gene
sets. To identify experiment-specific gene set enrichment, we developed the GSEA
InContext method that accounts for gene expression patterns within a background
set of experiments to identify statistically significantly enriched gene sets. We
evaluated GSEA-InContext on experiments using small molecules with known targets
to show that it successfully prioritizes gene sets that are specific to each
experiment, thus providing valuable insights that complement standard GSEA
analysis. Availability and implementation: GSEA-InContext implemented in Python,
Supplementary results and the background expression compendium are available at:
https://github.com/CostelloLab/GSEA-InContext.
PMID- 29950012
TI - DLBI: deep learning guided Bayesian inference for structure reconstruction of
super-resolution fluorescence microscopy.
AB - Motivation: Super-resolution fluorescence microscopy with a resolution beyond the
diffraction limit of light, has become an indispensable tool to directly
visualize biological structures in living cells at a nanometer-scale resolution.
Despite advances in high-density super-resolution fluorescent techniques,
existing methods still have bottlenecks, including extremely long execution time,
artificial thinning and thickening of structures, and lack of ability to capture
latent structures. Results: Here, we propose a novel deep learning guided
Bayesian inference (DLBI) approach, for the time-series analysis of high-density
fluorescent images. Our method combines the strength of deep learning and
statistical inference, where deep learning captures the underlying distribution
of the fluorophores that are consistent with the observed time-series fluorescent
images by exploring local features and correlation along time-axis, and
statistical inference further refines the ultrastructure extracted by deep
learning and endues physical meaning to the final image. In particular, our
method contains three main components. The first one is a simulator that takes a
high-resolution image as the input, and simulates time-series low-resolution
fluorescent images based on experimentally calibrated parameters, which provides
supervised training data to the deep learning model. The second one is a multi
scale deep learning module to capture both spatial information in each input low
resolution image as well as temporal information among the time-series images.
And the third one is a Bayesian inference module that takes the image from the
deep learning module as the initial localization of fluorophores and removes
artifacts by statistical inference. Comprehensive experimental results on both
real and simulated datasets demonstrate that our method provides more accurate
and realistic local patch and large-field reconstruction than the state-of-the
art method, the 3B analysis, while our method is more than two orders of
magnitude faster. Availability and implementation: The main program is available
at https://github.com/lykaust15/DLBI. Supplementary information: Supplementary
data are available at Bioinformatics online.
PMID- 29950013
TI - HFSP: high speed homology-driven function annotation of proteins.
AB - Motivation: The rapid drop in sequencing costs has produced many more (predicted)
protein sequences than can feasibly be functionally annotated with wet-lab
experiments. Thus, many computational methods have been developed for this
purpose. Most of these methods employ homology-based inference, approximated via
sequence alignments, to transfer functional annotations between proteins. The
increase in the number of available sequences, however, has drastically increased
the search space, thus significantly slowing down alignment methods. Results:
Here we describe homology-derived functional similarity of proteins (HFSP), a
novel computational method that uses results of a high-speed alignment algorithm,
MMseqs2, to infer functional similarity of proteins on the basis of their
alignment length and sequence identity. We show that our method is accurate (85%
precision) and fast (more than 40-fold speed increase over state-of-the-art).
HFSP can help correct at least a 16% error in legacy curations, even for a
resource of as high quality as Swiss-Prot. These findings suggest HFSP as an
ideal resource for large-scale functional annotation efforts. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29950014
TI - Haplotype phasing in single-cell DNA-sequencing data.
AB - Motivation: Current technologies for single-cell DNA sequencing require whole
genome amplification (WGA), as a single cell contains too little DNA for direct
sequencing. Unfortunately, WGA introduces biases in the resulting sequencing
data, including non-uniformity in genome coverage and high rates of allele
dropout. These biases complicate many downstream analyses, including the
detection of genomic variants. Results: We show that amplification biases have a
potential upside: long-range correlations in rates of allele dropout provide a
signal for phasing haplotypes at the lengths of amplicons from WGA, lengths which
are generally longer than than individual sequence reads. We describe a
statistical test to measure concurrent allele dropout between single-nucleotide
polymorphisms (SNPs) across multiple sequenced single cells. We use results of
this test to perform haplotype assembly across a collection of single cells. We
demonstrate that the algorithm predicts phasing between pairs of SNPs with higher
accuracy than phasing from reads alone. Using whole-genome sequencing data from
only seven neural cells, we obtain haplotype blocks that are orders of magnitude
longer than with sequence reads alone (median length 10.2 kb versus 312 bp), with
error rates <2%. We demonstrate similar advantages on whole-exome data from 16
cells, where we obtain haplotype blocks with median length 9.2 kb-comparable to
typical gene lengths-compared with median lengths of 41 bp with sequence reads
alone, with error rates <4%. Our algorithm will be useful for haplotyping of rare
alleles and studies of allele-specific somatic aberrations. Availability and
implementation: Source code is available at https://www.github.com/raphael-group.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29950015
TI - ISMB 2018 PROCEEDINGS PAPERS COMMITTEE.
PMID- 29950016
TI - The Kappa platform for rule-based modeling.
AB - Motivation: We present an overview of the Kappa platform, an integrated suite of
analysis and visualization techniques for building and interactively exploring
rule-based models. The main components of the platform are the Kappa Simulator,
the Kappa Static Analyzer and the Kappa Story Extractor. In addition to these
components, we describe the Kappa User Interface, which includes a range of
interactive visualization tools for rule-based models needed to make sense of the
complexity of biological systems. We argue that, in this approach, modeling is
akin to programming and can likewise benefit from an integrated development
environment. Our platform is a step in this direction. Results: We discuss
details about the computation and rendering of static, dynamic, and causal views
of a model, which include the contact map (CM), snaphots at different
resolutions, the dynamic influence network (DIN) and causal compression. We
provide use cases illustrating how these concepts generate insight. Specifically,
we show how the CM and snapshots provide information about systems capable of
polymerization, such as Wnt signaling. A well-understood model of the KaiABC
oscillator, translated into Kappa from the literature, is deployed to demonstrate
the DIN and its use in understanding systems dynamics. Finally, we discuss how
pathways might be discovered or recovered from a rule-based model by means of
causal compression, as exemplified for early events in EGF signaling.
Availability and implementation: The Kappa platform is available via the project
website at kappalanguage.org. All components of the platform are open source and
freely available through the authors' code repositories.
PMID- 29950017
TI - A gene-phenotype relationship extraction pipeline from the biomedical literature
using a representation learning approach.
AB - Motivation: The fundamental challenge of modern genetic analysis is to establish
gene-phenotype correlations that are often found in the large-scale publications.
Because lexical features of gene are relatively regular in text, the main
challenge of these relation extraction is phenotype recognition. Due to
phenotypic descriptions are often study- or author-specific, few lexicon can be
used to effectively identify the entire phenotypic expressions in text,
especially for plants. Results: We have proposed a pipeline for extracting
phenotype, gene and their relations from biomedical literature. Combined with
abbreviation revision and sentence template extraction, we improved the
unsupervised word-embedding-to-sentence-embedding cascaded approach as
representation learning to recognize the various broad phenotypic information in
literature. In addition, the dictionary- and rule-based method was applied for
gene recognition. Finally, we integrated one of famous information extraction
system OLLIE to identify gene-phenotype relations. To demonstrate the
applicability of the pipeline, we established two types of comparison experiment
using model organism Arabidopsis thaliana. In the comparison of state-of-the-art
baselines, our approach obtained the best performance (F1-Measure of 66.83%). We
also applied the pipeline to 481 full-articles from TAIR gene-phenotype manual
relationship dataset to prove the validity. The results showed that our proposed
pipeline can cover 70.94% of the original dataset and add 373 new relations to
expand it. Availability and implementation: The source code is available at
http://www.wutbiolab.cn: 82/Gene-Phenotype-Relation-Extraction-Pipeline.zip.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29950018
TI - Accurate prediction of orthologs in the presence of divergence after duplication.
AB - Motivation: When gene duplication occurs, one of the copies may become free of
selective pressure and evolve at an accelerated pace. This has important
consequences on the prediction of orthology relationships, since two orthologous
genes separated by divergence after duplication may differ in both sequence and
function. In this work, we make the distinction between the primary orthologs,
which have not been affected by accelerated mutation rates on their evolutionary
path, and the secondary orthologs, which have. Similarity-based prediction
methods will tend to miss secondary orthologs, whereas phylogeny-based methods
cannot separate primary and secondary orthologs. However, both types of orthology
have applications in important areas such as gene function prediction and
phylogenetic reconstruction, motivating the need for methods that can distinguish
the two types. Results: We formalize the notion of divergence after duplication
and provide a theoretical basis for the inference of primary and secondary
orthologs. We then put these ideas to practice with the Hybrid Prediction of
Paralogs and Orthologs (HyPPO) framework, which combines ideas from both
similarity and phylogeny approaches. We apply our method to simulated and
empirical datasets and show that we achieve superior accuracy in predicting
primary orthologs, secondary orthologs and paralogs. Availability and
implementation: HyPPO is a modular framework with a core developed in Python and
is provided with a variety of C++ modules. The source code is available at
https://github.com/manuellafond/HyPPO. Supplementary information: Supplementary
data are available at Bioinformatics online.
PMID- 29950019
TI - A scalable estimator of SNP heritability for biobank-scale data.
AB - Motivation: Heritability, the proportion of variation in a trait that can be
explained by genetic variation, is an important parameter in efforts to
understand the genetic architecture of complex phenotypes as well as in the
design and interpretation of genome-wide association studies. Attempts to
understand the heritability of complex phenotypes attributable to genome-wide
single nucleotide polymorphism (SNP) variation data has motivated the analysis of
large datasets as well as the development of sophisticated tools to estimate
heritability in these datasets. Linear mixed models (LMMs) have emerged as a key
tool for heritability estimation where the parameters of the LMMs, i.e. the
variance components, are related to the heritability attributable to the SNPs
analyzed. Likelihood-based inference in LMMs, however, poses serious
computational burdens. Results: We propose a scalable randomized algorithm for
estimating variance components in LMMs. Our method is based on a method-of-moment
estimator that has a runtime complexity O(NMB) for N individuals and M SNPs
(where B is a parameter that controls the number of random matrix-vector
multiplications). Further, by leveraging the structure of the genotype matrix, we
can reduce the time complexity to O(NMBmax( log?3N, log?3M)). We demonstrate the
scalability and accuracy of our method on simulated as well as on empirical data.
On standard hardware, our method computes heritability on a dataset of 500 000
individuals and 100 000 SNPs in 38 min. Availability and implementation: The RHE
reg software is made freely available to the research community at:
https://github.com/sriramlab/RHE-reg.
PMID- 29950020
TI - Deep neural networks and distant supervision for geographic location mention
extraction.
AB - Motivation: Virus phylogeographers rely on DNA sequences of viruses and the
locations of the infected hosts found in public sequence databases like GenBank
for modeling virus spread. However, the locations in GenBank records are often
only at the country or state level, and may require phylogeographers to scan the
journal articles associated with the records to identify more localized
geographic areas. To automate this process, we present a named entity recognizer
(NER) for detecting locations in biomedical literature. We built the NER using a
deep feedforward neural network to determine whether a given token is a toponym
or not. To overcome the limited human annotated data available for training, we
use distant supervision techniques to generate additional samples to train our
NER. Results: Our NER achieves an F1-score of 0.910 and significantly outperforms
the previous state-of-the-art system. Using the additional data generated through
distant supervision further boosts the performance of the NER achieving an F1
score of 0.927. The NER presented in this research improves over previous systems
significantly. Our experiments also demonstrate the NER's capability to embed
external features to further boost the system's performance. We believe that the
same methodology can be applied for recognizing similar biomedical entities in
scientific literature.
PMID- 29950022
TI - ISMB 2018 proceedings.
PMID- 29950021
TI - LONGO: an R package for interactive gene length dependent analysis for neuronal
identity.
AB - Motivation: Reprogramming somatic cells into neurons holds great promise to model
neuronal development and disease. The efficiency and success rate of neuronal
reprogramming, however, may vary between different conversion platforms and cell
types, thereby necessitating an unbiased, systematic approach to estimate
neuronal identity of converted cells. Recent studies have demonstrated that long
genes (>100 kb from transcription start to end) are highly enriched in neurons,
which provides an opportunity to identify neurons based on the expression of
these long genes. Results: We have developed a versatile R package, LONGO, to
analyze gene expression based on gene length. We propose a systematic analysis of
long gene expression (LGE) with a metric termed the long gene quotient (LQ) that
quantifies LGE in RNA-seq or microarray data to validate neuronal identity at the
single-cell and population levels. This unique feature of neurons provides an
opportunity to utilize measurements of LGE in transcriptome data to quickly and
easily distinguish neurons from non-neuronal cells. By combining this conceptual
advancement and statistical tool in a user-friendly and interactive software
package, we intend to encourage and simplify further investigation into LGE,
particularly as it applies to validating and improving neuronal differentiation
and reprogramming methodologies. Availability and implementation: LONGO is freely
available for download at https://github.com/biohpc/longo. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29950024
TI - Workloads make nurses and midwives walk.
PMID- 29950025
TI - Support for one on one midwifery care.
PMID- 29950026
TI - New guidelines on drug-resistant CRE.
PMID- 29950027
TI - NSW nurse led refugee health service makes a difference.
PMID- 29950028
TI - Syrian refugee health crisis.
PMID- 29950029
TI - Advocacy of those who care.
AB - Equity and access to health care was the theme of the International Council of
Nurses' 25th Quadrennial Congress, held in Melbourne earlier this year. Speakers
referred to links between economic status and a person's ability to access even
basic health care services.
PMID- 29950030
TI - Postpartum hemorrhage reporting in Australia.
AB - Research is underway to explore inconsistencies in postpartum haemorrhage (PPH)
rates nationwide with the rising rate of PPH identified as an issue in Australia.
PMID- 29950031
TI - Taking responsibility for health care.
AB - Advertising through mass media has been a useful strategy in the public health
campaign to expose the population to messages on the negative impact of lifestyle
choices on our general health such as smoking and obesity, which is now
recognised as a growing public health issue.
PMID- 29950032
TI - Encouraging responsible drinking... with a focus on the Northern Territory.
AB - Alcohol consumption per capita in the Northern Territory is substantially higher,
at 13.3 litres than the national figure of 9.02 litres (People's Alcohol Action
Coalition 2012 and Department of Health and Ageing 2009a). As well as measures to
reduce supply, continued efforts to reduce the demand for alcohol have been
implemented, including the use of public awareness campaigns.
PMID- 29950033
TI - 'Death with dignity' - doubts and demands.
AB - Most people reading the following words would probably agree with the sentiments
expressed: '... die with respect, die with a degree of dignity [...]. We must die
with some dignity .... Let's, let's be dignified' (Jones 1978).
PMID- 29950034
TI - Wellbeing.
AB - We all know a well-balanced diet is important for our general health and
wellbeing, but how easy is it to maintain when working rotating shifts and
dealing with busy workloads?
PMID- 29950035
TI - Evaluating nurse practitioner models of care in aged care: getting it right and
the cost of getting it wrong.
AB - Economics can play a role in the formation of health policy. The conundrum of how
to continue to provide quality health care in the context of the projected ageing
of the Australian population and increased burden of chronic disease has driven
the impetus to explore new models of care of aged Australians.
PMID- 29950036
TI - Volunteer.
PMID- 29950037
TI - A love for saving lives.
AB - Seeing the smiling face of a woman whose husband had been rushed into the
Emergency Department with a life-threatening cardiac condition just days earlier,
reaffirmed to Flinders Medical Centre (FMC) Clinical Nurse Andrew Douglas why he
loves his job.
PMID- 29950038
TI - Comprehensive geriatric 1 assessment and the assessment of depression in the
elderly.
AB - As our population ages, the need to identify and manage risks to elderly people's
health becomes more pressing.
PMID- 29950039
TI - Cornell Scale for Depression in Dementia.
AB - This scale should be administered by a health professional with appropriate
psychological training for maximum screening effect. It requires interview of an
informant and observation of and interview with the client being screened. This
scale is effective for clients both with and without cognitive impairment.
PMID- 29950040
TI - 100 years of school nursing in Victoria.
AB - This year celebrates 100 years since the introduction of the Victorian School
Nursing Program in 1913 when school nurses were brought in to assist medical
officers. School nursing objectives had more of a medical view to health and
wellbeing.
PMID- 29950041
TI - Camp promotes mental health and fun.
AB - The annual Challenge by Choice Camp at Woodman Point in Western Australia is a
consumer-led initiative which gives people with mental health conditions a chance
to relax, have fun, build friendships and learn new skills in a safe and
supportive environment.
PMID- 29950042
TI - Mental Health Education and Training: women's health, mind and body.
AB - Mental health (learning and development coordinator) and women's health services
collaboratively planned a workshop to meet the training needs of mental health
workers in Sydney's west.
PMID- 29950043
TI - Mediterranean diet to be tested.
AB - A traditional Mediterranean-style diet will be offered to mental health consumers
in a new pilot study at Noarlunga's Community Rehabilitation Centre, the Trevor
Parry Centre in South Australia, to investigate the impact of improved diet on
health and wellbeing.
PMID- 29950044
TI - New BPD Management Guidelines.
PMID- 29950045
TI - Nurse-led dementia care.
AB - Community nurses who visit older people in their own homes could hold the key to
identifying people predisposed to dementia.
PMID- 29950046
TI - Psychosocial intervention and recovery training: Tears and triumphs.
AB - The management of severe mental illness should not only involve medication, but
psychosocial interventions.
PMID- 29950047
TI - Innovation in mental health nursing education.
AB - CQUniversity's strength in mental health nursing has been enhanced by what is
thought to be the first full time academic employed specifically to work from a
lived experience of significant mental health difficulties, mental health service
use and recovery.
PMID- 29950049
TI - Awareness building of sexual health concerns.
AB - It is commonly reported across a variety of clinical fields that nurses avoid the
inclusion of sexual health in the care they provide with similar reasons for this
avoidance being reported.
PMID- 29950048
TI - Hold my hand and walk with me: Empathy on the mental health inpatient unit.
AB - Empathy - the ability to take another's perspective and experience emotional and
sympathetic reactions to their situation - is a core process in building
therapeutic relationships between nurses and the individuals they care for. The
question of how empathy operates when there is some disagreement or discord
(conflict) between staff and persons in mental health care was the focus of our
recent research.
PMID- 29950050
TI - Developing acute mental health services in Perth.
AB - John of God Health Care is building the St John of God Midland Public and Private
Hospitals in Midland, Perth. Due to open in late 2015, these contemporary
facilities combined with our distinctive compassionate care are aimed to
contribute to a healthy future for the people of Midland and surrounding
communities.
PMID- 29950051
TI - Specialist nursing role to address poor physical health.
AB - It is now well known that people diagnosed with mental illness have poorer health
behaviours, lower levels of physical activity, multiple comorbid chronic health
conditions and poorer health compared to the general population (Scott et al
2012).
PMID- 29950052
TI - Specialty Competencies for Nurse Practitioners.
AB - Generic competency standards for nurse practitioners have been developed and
adopted by the national regulatory body in Australia, but to date there has been
little attention directed to the identification of specialty clinical
competencies for nurse practitioners, or an educational governance framework that
supports development of this specialty clinical competence.
PMID- 29950053
TI - Health care systems that harm.
PMID- 29950054
TI - [Treatise on Febrile Diseases and critical care medicine: exploring connotation
of original, dosage, and essence of six meridians from perspective of critical
care medicine and integrative medicine].
AB - Treatise on Febrile Diseases is one of the greatest classics in traditional
Chinese medicine. Currently, so many key scientific problems including unclear
connotation of the original, dosage of Chinese herbal medicine, and the essence
of the six meridians were identified. On the basis of years of clinical
experience in critical care medicine, it was advocated that the connotation of
Treatise on Febrile Diseases should be explored from the perspective of critical
care medicine and integrative medicine. It was identified that, the traditional
study from the perspective of pathogenesis and textual research couldn't meet the
current clinical needs due to its repeated deduction and circular argument in
conceptual terms and unclear diagnosis and prognosis of modern diseases. The
concept of exogenous febrile disease is the narrow sense, the essence of which
may be acute febrile infectious diseases. Treatise on Febrile Diseases is a
monographs for critical care medicine. The clinical manifestation of so many
critical care medicine can be identified in Treatise on Febrile Diseases. The
distinction standard of Treatise on Febrile Diseases and Synopsis of Golden
Chamber is not external injury but contagious disease. The dosage problem in
Treatise on Febrile Diseases mainly refers to large dose. The essence of six
meridians in Treatise on Febrile Diseases is severe infection. Six meridians are
different stages of severe infection, including the inflammation-based three Yang
stages and deficiency-based three Yin stages. Additionally, the six meridians
could be recognized by look, while not speculation. The struggle between cold and
warm schools could be unified based on our research. The most direct and
fundamental methods in studying Treatise on Febrile Diseases lies in critical
care medicine and integrative medicine. The modern research of Treatise on
Febrile Diseases is intensely calling for new treatment principle based on
pathogenesis combined with pathology and property combined with pharmacology.
Therefore, cultivation of ability in critical care medicine and integrative
medicine should be emphasized in future studies.
PMID- 29950055
TI - [Chinese classical formulas Ephedra associated prescriptions for treatment of
skin diseases].
AB - Chinese classical formulas, firstly recorded in Shanghan Zabing Lun by Zhang
Zhongjing in the Han dynasty, have been widely used by traditional Chinese
medicine physicians for thousands of years due to its good compatibility, strict
structures, significant clinical efficacy and less adverse effects. Ephedra
associated prescriptions, widely used in the treatment of skin diseases, are
famous representative prescriptions in Chinese classical formulas. The commonly
used Ephedra associated prescriptions include Mahuang Lianqiao Chixiaodou
decoction, Maxing Shigan decoction, Maxing Yigan decoction, Mahuang decoction,
Mahuang Jiazhu decoction, Guizhi Mahuang Geban decoction, and Guizhi Eryue Biyi
decoction. Skin allergy is an allergic reaction, manifested as erythema, papules,
and itching. It has been identified that Guizhi Mahuang Geban decoction (1/2
Guizhi decoction + 1/2 Mahuang decoction) is effective in dispersing wind and
cold, relieving exterior syndrome and dredging the collaterals, so it can be used
to treat skin allergy caused by pathogenic wind-cold. Guizhi Eryue Biyi decoction
(1/4 Guizhi decoction + 1/8 Yuebi decoction) is effective in dispersing wind and
cold, relieving exterior syndrome and clearing heat, so it is mainly used for the
syndrome of wind-cold tightening superficies and heat transformed from wind-cold.
Additionally, Mahuang Lianqiao Chixiaodou decoction can relieve exterior
syndrome, clear heat and remove dampness, mainly for the dampness and heat
depression in the muscle surface. It is found that Guizhi Mahuang Geban decoction
and Guizhi Eryue Biyi decoction have certain efficacy for skin allergies, while
Mahuang Lianqiao Chixiaodou decoction has significant efficacy for urticaria,
acute and chronic eczema, etc. It has been identified that if the conditions of
Ephedra associated prescriptions are well mastered by traditional Chinese
medicine physicians, they could be widely applied to treat exogenous diseases and
miscellaneous diseases.
PMID- 29950056
TI - [Thought and method of classic formulae in treatment of chronic cough].
AB - Chronic cough is a common clinical disease with complex etiology, which is easily
misdiagnosed and mistreated. Chronic cough guideline has been developed based on
the modern anatomical etiology classification, and it may improve the level of
diagnosis and treatment. Common causes of chronic cough are as follows: cough
variant asthma, upper airway cough syndrome, eosinophilic bronchitis,
gastroesophageal reflux-related cough, post-infectious cough, etc. There is a
long history and rich experience in treatment of cough in traditional Chinese
medicine which is characterized by syndrome differentiation. The four elements of
pathogenesis for chronic cough include wind, phlegm, fire, and deficiency.
Classic formula is widely used in the treatment of chronic cough, and the focus
is on prescriptions corresponding to syndromes. This article attempts to explore
the thought and method of classic formulae in treatment of chronic cough based on
three perspectives: differentiation of etiology, pathogenesis and formula
syndrome. Three medical cases are selected at last in order to prove its
correction.
PMID- 29950057
TI - [Research progress in modern clinical application and mechanism of Guizhi
decoction].
AB - Guizhi decoction come from Typhoid Theory written by Zhang Zhongjing, a famous
physician in the Han dynasty. It is called "the leading group of the group" by
later doctors. At present, Guizhi decoction is widely used in treatment of many
diseases of internal, external, gynecologic and other diseases. This article
discusses the clinical application and mechanism of Guizhi decoction in two
aspects. This article expounds that Guizhi decoction is widely used in colds,
febrile diseases, various perspiration, digestive system diseases and respiratory
diseases, Some diseases, such as ear, nose and throat disease, nervous system
disease, cardiac autonomic neuropathy, and bone and joint disease. The mechanism
of Guizhi decoction in the treatment of diseases may be related to the mechanism
of biaxial regulation of body temperature and gastrointestinal motility, mucosal
immune intervention, secretion of sweat glands, inflammation immune function and
myocardial protective effect and so on.
PMID- 29950058
TI - [Analysis of protective effects of Chaihu Jia Longgu Muli Tang against ischemic
stroke by combining traditional Chinese medicine pathogenesis and efficacy with
modern pathology and pharmacology].
AB - Chaihu Jia Longgu Muli Tang is a classical Chinese formulas treating Shaoyang
syndrome complicated with Yangming syndrome according to Treatise on Febrile
Diseases. This formula is used in mental disorder, nervous system, gynecologic,
andrologic, and cardiovascular disease. However, its therapeutic effect on
ischemia stroke and its mechanism is far from clear. In clinical practice, we
have found that this formula is effective in treating ischemic stroke, which can
shorten the course of the disease and reduce recurrence. The characteristics of
this formula include: Shaoyang cardinal disadvantageous syndrome, mental and
nervous symptoms, retained fluid punched upward syndrome and accumulation of heat
in the stomach and intestines. By combining traditional Chinese medicine (TCM)
pathogenesis and efficacy with modern pathology and pharmacology, we proposed
that the TCM pathogenesis of stroke, which is characterized by hyperactivity of
heat combining with phlegm, stasis and water drink, is consistent with syndromes
and corresponding pathology targeted by Chaihu Jia Longgu Muli Tang, including
the stress brain edema zone around the ischemic lesion, the increase of
intracranial pressure, the excitement of sympathetic nerve, the release of
monoamine neurotransmitter, the hypofunction of autonomic nervous system after
stroke, and gastrointestinal stress response. Furthermore, the pharmacological
mechanism of Chaihu Jia Longgu Muli Tang is concentrated on regulation the
neuroendocrinology system centered by hypothalamic-pituitary-adrenal axis (HPA),
participating in the process of neuron regeneration and apoptosis, oxidative
stress, hyperactivity of sympathetic nerve, and inflammatory reaction. These
pathological processes are consistent with the pathological changes after
ischemic stroke. Therefore, Chaihu Jia Longgu Muli Tang is a key formula for
treating ischemic stroke.
PMID- 29950059
TI - [Study on classic preparations].
AB - In this paper, classic preparations in Treatise on Febrile Diseases were
systematically investigated to obtain their process parameters, and provide
literature evidence and technical support for drug research and development. This
paper includes the following sections: drug dose, solvents, excipients, and
process parameters of classic preparations. The drug dose in Treatise on Febrile
Diseases was not consistent with that in Pharmacopoeia of the People's Republic
of China 2015, for example, "Yi-Liang" was about 15.625 g, and "Yi-Sheng" was
about 200 mL. The solvents of classic preparations can be divided into two types:
wine and water. There were eight kinds of water: water, "Dongliu water" "Ganlan
water" "acid pulp" "Jinghua water" "Lao water" "Mafei Tang" "spring water". There
four kinds of wines: "wine" "Bai wine" "Qing wine" "Ku wine". There were two
kinds of excipients: rice and honey. Classic prescription powder had two kinds of
processes: "whole prescription powder" and "Yidaoshai Hezhizhi powder". Classic
prescription pills had three kinds of processes: direct whole prescription
pilling, pilling after extraction, and pilling with excipients after smashing.
Classic prescription decoction had six kinds of processes: "wine Tang", "Mafei
Tang", "Jingmi Tang", "Mijian Tang", "water Tang" "Zhugao Tang". Drug dose,
solvents, excipients, processes and other key parameters of classic preparations
were systemically reviewed in this study, and the process parameters were
clarified to provide literature evidence and technical support for drug
development.
PMID- 29950060
TI - [Exploration on method and strategy of Gegen decoction from its novel application
in primary dysmenorrhea].
AB - Many classical prescriptions still have superior clinical values nowadays, and
their modern studies also have far-reaching scientific research demonstration
values. Gegen decoction, a representative prescription for common cold due to
wind-cold, can treat primary dysmenorrhea due to cold and dampness, characterized
by continuous administration without recurrence. It is not only in accordance
with the principle of homotherapy for heteropathy, but also demonstrates the
unique feature of traditional Chinese medicine of relieving the primary and
secondary symptoms simultaneously. This article aimed to discuss the method and
strategy of Gegen decoction study based on the discovery of its novel application
in treatment of primary dysmenorrhea and previous research progress of our group.
It was assumed that modern medicine and biology studies, as well as chemical
research based on biological activity should be used for reference. Principal
active ingredients (groups) in Gegen decoction could be accurately and
effectively identified, and its possible mechanism in treatment of primary
dysmenorrhea could be eventually elucidated as well. Simultaneously, the
theoretical and clinical advantages of traditional Chinese medicine were explored
in this paper, focusing on the compatibility characteristics of Gegen decoction.
The research hypothesis showed the necessity of following the characteristics and
advantages of traditional Chinese medicine in the modern research and reflected
the importance of basic research based on the clinical efficacy, expecting to
provide some ideas and methods for reference for further modern studies of
classical prescriptions.
PMID- 29950061
TI - [Connotation interpretation of "only one syndrome is evident for disease" in
Treatise on Febrile Diseases by Zhang Zhongjing].
AB - "Only one syndrome is evident for disease", a clinical guiding ideology in the
Treatise on Febrile Diseases proposed by Zhang Zhongjing, has caused widespread
controversy among physicians over the ages. The core lies in the divergence of
the understanding of "one syndrome". The reason is that although many physicians
sum up experience on the basis of their clinical experience, the premise of the
clinical environment is ignored when interpreting the connotation. On the one
hand, "only one syndrome is evident for disease" emphasizes the flexibility of
grasping the main symptoms clinically. On the other hand, it emphasizes the
evidence sufficiency of "one syndrome" as the basis for diagnosis. Generally
speaking, specific symptoms are higher evidence as a basis for diagnosis.
However, because of the clinical complexity, the symptoms with lower specificity,
less targeting and lower evidence strength in common cases may become the key
points of the final prescription selection in specific cases sometimes,
increasing the strength of evidence and becoming the only important factor in
determining the overall situation. In addition to the objective clinical
conditions, some subjective factors such as clinical level and academic quality
of the physicians are also important factors that affect the clinical application
of "only one syndrome is evident for disease". Therefore, it is necessary to not
only pay attention to the clinical objective conditions, but also try to improve
the physicians' clinical level, appreciate the "only one syndrome is evident for
disease" thought in the clinical environment, which is the key to solve this
problem.
PMID- 29950062
TI - [Strategies of interventing complications in hemodialysis with classical
prescriptions from clinical cases].
AB - There are 400 thousand patients with long-term hemodialysis in China nowadays.
Hemodialysis, as the most common alternative to renal replacement therapy,
prolongs the life span of patients with end stage renal failure. However, there
are still many complications of hemodialysis treatment. These complications
reduce the quality of life of patients and may even endanger their life, and
sometimes they are difficult to deal with. Classical prescriptions, commonly
referred to as classical effective prescriptions in modern medicine, mainly
indicating the formulas recorded in Treatise on Febrile Diseases and Synopsis of
Golden Chamber, were relative to contemporary prescriptions emerging after Song
and Yuan dynasties. Prescriptions corresponding to syndromes means one-to-one
correspondence between syndromes and prescriptions, with many advantages and that
is the key of clinical efficacy. Many complications of hemodialysis patients have
typical clinical manifestations, which can match the syndromes corresponding to
classical prescriptions, thus quickly relieving the symptoms of patients in
clinical application. Six clinical cases of dialysis muscle spasm, disequilibrium
syndrome, restless legs syndrome, uremic encephalopathy, post dialysis
arrhythmia, and secondary hyperparathyroidism were used in this paper, to explore
the intervention strategies for hemodialysis related complications.
PMID- 29950063
TI - [Effects of different concentrations of nitrogen,phosphorus and potash on
Glycyrrhiza uralensis and its relationship with soil element content].
AB - With annual Glycyrrhiza uralensis seedlings as experimental material, using
"3414" optimal regression design and applied fertilizer, through the sampling of
G. uralensis at harvest, root fresh weight and content of active components were
measured in Lanzhou, Bayan Nur city, Chifeng, Jiuquan. Combined with NPK content
in soil, potted experiments were used to study the effects of different nitrogen
and phosphorus ratios on the dry matter accumulation and accumulation of active
components of G. uralensis. The results reported as follows: the optimum
fertilizer treatment in Lanzhou, Bayan Nur city, Chifeng, Jiuquan was
N1P2K1,N2P2K1,N1P1K2 and N2P1K2, respectively. The efforts of single fertilizer
on the fresh root weight acted as parabolic type.There was no significant effect
of fertilizer treatment on the accumulation of active components of G. uralensis.
Furthermore, in terms of nitrogen and phosphorus, the type of fertilizers that
restricted the growth of the region was the type of elements with lower content
in the soil. The optimal fertilizer usage was in inverse proportion to content of
elements in soil. When the content of phosphorus in soil was low, nitrogen
fertilizer and potash fertilizer showed positive interaction with phosphorus
fertilizer, whereas, they showed negative interaction.
PMID- 29950064
TI - [Effect of compound planting on soil physical and chemical properties and soil
enzyme activities of Salvia miltiorrhiza].
AB - The effects of four kinds of different plant populations on the soil physical and
chemical properties and soil enzyme activities of Salvia miltiorrhiza were
analyzed by setting up four kinds of mixed planting groups, such as S.
miltiorrhiza and Cassia obtusifolia, Capsicum annuum, Perilla frutescens and Zea
mays. And through the root isolation treatment, we preliminarily explored the
formation mechanism of the four kinds of matching plants of soil physical and
chemical properties and soil enzyme activities of S. miltiorrhiza, and chose the
matching plants suitable for the establishment of the compound population with S.
miltiorrhiza,and provided the basis for constructing high efficiency compound
planting pattern of S. miltiorrhiza. The results showed that there were
significant differences in soil physical and chemical properties and soil enzyme
activitiesof Salvia miltiorrhiza in different compound population mixed.The
combination of C. obtusifolia, P. frutescens, Z. mays and S. miltiorrhiza mixed
planting were all reduced the soil cation exchange capacity and soil enzyme
activities, and increased the soil electric conductivity. The compound planting
of P. frutescens and S. miltiorrhiza increased the soil cation exchange capacity
and soil enzyme activities, and reduced the soil electric conductivity.
Therefore,The compound planting population of P. frutescens and S. miltiorrhiza
is conducive to improve soil physical and chemical properties and increase soil
microbial activity, which is the best collocation species of S. miltiorrhiza.
PMID- 29950065
TI - [Comparative analysis on seedling growth dynamics and physiological indices of
Bupleurum smithii var. parvifolium and B. scorzonerifolium].
AB - With Bupleurum smithii var. parvifolium and B. scorzonerifolium as test objects,
in order to provide a theoretical basis for the introduction and domestication of
B. smithii var. parvifolium, the growth and development dynamics of seedlings,
biomass accumulation, the content of malonaldehyde(MDA), the activity of
antioxidase such as SOD, POD, CAT and APX between them were comparatively
analyzed by direct sowing culture in the open field. The results indicated that
the morphological index and the biomass accumulation of B. smithii var.
parvifolium such as root diameter, root length, plant height and leaf number were
inferior to B. scorzonerifolium, the antioxidase SOD and POD activity of B.
smithii var. parvifolium was significantly inferior to B. scorzonerifolium
(P<0.05), the antioxidase CAT and APX activity of B. smithii var. parvifolium was
inferior to B. scorzonerifolium but the difference wasn't significant, while MDA
content was superior to B. scorzonerifolium(P<0.05). Thus, compared with
cultivated B. scorzoneri folium, the plant growth velocity of wild B. smithii
var. parvifolium was relatively slower and its resistance was relatively weaker
after introduction and domestication.
PMID- 29950066
TI - [Genotype, environment and their interactions of functional components in Rheum
palmatum].
AB - Eight kinds of provenance of Rheum palmatum collected from 4 provinces Sichuan,
Ningxia, Gansu, Shannxi as test materials, which were transplanted under 3
different environments by using complete randomized block design with three
replicates. The contents of the chemical components was determined by HPLC. This
study aimed at analyzing the effect of genotype, environment and their
interactions on the 4 kinds of functional components (phenolic acids, bianthrone,
free anthraquinones and combined anthraquinones) in 14 kinds of active components
of R. palmatum, in order to provide a theoretical basis for the selection of
cultivated R. palmatum in high quality producing area and excellent provenance.
The functional components of R. palmatum were influenced by genotype and
environment. The content of phenolic acids was mainly influenced by environment,
and the other three kinds of functional components were affected by environment
and their interactions. The proportion of environment was larger. The cultivation
quality of R. palmatum should give priority to environment, then choose a
provenance. Sichuan may be beneficial in accumulation of free anthraquinones in
R. palmatum, Gansu may facilitate the binding of combined anthraquinone, phenolic
acids and bianthrone content. Preliminary inference based on the content and
proportion of efficacy components, P2 could be potential special medicinal
germplasm that have function of heat-clearing and detoxifying drugs. P6 could be
potential special medicinal germplasm that activate blood circulation to
dissipate blood stasis. P7 and P1 could all be potential specialmedicinal
germplasms that exist diarrhea attack characters. The results of this study have
important guiding significance for the production of rhubarb precision medicinal
materials.
PMID- 29950067
TI - [SSR loci information analysis in transcriptome of Andrographis paniculata].
AB - To study the SSR loci information and develop molecular markers, a total of 43
683 Unigenes in transcriptome of Andrographis paniculata were used to explore
SSR. The distribution frequency of SSR and the basic characteristics of repeat
motifs were analyzed using MicroSAtellite software, SSR primers were designed by
Primer 3.0 software and then validated by PCR. Moreover, the gene function
analysis of SSR Unigene was obtained by Blast. The results showed that 14 135 SSR
loci were found in the transcriptome of A. paniculata, which distributed in 9 973
Unigenes with a distribution frequency of 32.36%. Di-nucleotide and Tri
nucleotide repeat were the main types, accounted for 75.54% of all SSRs. The
repeat motifs of AT/AT and CCG/CGG were the predominant repeat types of Di
nucleotide and Tri-nucleotide, respectively. A total of 4 740 pairs of SSR
primers with the potential to produce polymorphism were designed for maker
development. Ten pairs of primers in 20 pairs of randomly picked primers produced
fragments with expected molecular size. The gene function of Unigenes containing
SSR were mostly related to the basic metabolism function of A. paniculata. The
SSR markers in transcriptome of A. paniculata show rich type, strong specificity
and high potential of polymorphism, which will benefit the candidate gene mining
and marker-assisted breeding.
PMID- 29950068
TI - [Rapid identification of Gekko gecko by loop-mediated isothermal amplification
based on 12S rRNA sequence].
AB - Gekko gecko (Tokay Gecko) is a valuable traditional Chinese medicine. In this
study, the loop-mediated isothermal amplification (LAMP) technique was introduced
for visual rapid identification of G. gecko from adulterants. A total of sixty
five 12S rRNA sequences of fourteen species of G. gecko and its adulterants were
obtained. The results showed that G. gecko could be identified from its
adulterants through BLAST analysis based on 12S rRNA regions. The 12S rRNA
sequences of ten batches of G. gecko were conserved. There were only two
haplotypes and three variation sites in the available regions for primers design.
Six specific LAMP primers were successfully designed online based on 12S rRNA
sequences. The visual rapid detection of G. gecko could be achieved with the
optimized conditions (64 degrees C for 1 h and 80 degrees C for 5 min). And the
required minimal template concentration was 5 MUg.L-1 while conventional PCR with
0.5 mg.L-1. Consequently, the LAMP method established from this study was rapid,
specific, highly sensitive, and simple. It could be applied to detect G. gecko
from its adulterants efficiently.
PMID- 29950069
TI - [Effects of toxic fractions of Euphorbiae Ebracteolatae Radix on toxicity of mice
intestinal tract and colon aquaporins expression level before and after vinegar
processing].
AB - To investigate the toxicity changes of Euphorbiae Ebracteolatae Radix (EER)
before and after vinegar processing, toxic diterpenoids were concentrated with
chloroform as extraction solvent from EER. Then the residue was extracted for non
chloroform extract with 95% ethanol and water after extraction with chloroform.
The chloroform extraction of vinegar processed EER was prepared with the same
method. The mice received the drug by oral administration. Moisture content in
mice feces, duodenum and colon tissue, aquaporin AQP1, AQP3, AQP4 protein
expression levels were assayed as the indexes to investigate the toxicity
variation of chloroform fraction, non-chloroform fraction, as well as intestinal
tract toxicity before and after vinegar processing of EER. The results showed
that the chloroform fraction extracted from EER could significantly increase the
moisture content in mice feces, duodenum and colon, and decrease AQP1 protein
expression level, increase AQP3 and AQP4 protein expression levels in the colon.
The intestinal toxicity of the chloroform extract was significantly higher than
that of non-chloroform extract. The moisture content in mice feces, duodenum and
colon was significantly decreased, and the AQPs protein expression tended to be
normal in the colon after vinegar processing. The results showed that the
chloroform fraction extracted from EER could lead to diarrhea, intestinal edema,
and the intestinal toxicity action was associated with interfering AQPs protein
expression and promoting intestinal fluid transport disorder in mice. Vinegar
processing could reduce intestinal toxicity of EER, so vinegar processing was
considered to be the scientific processing method of EER.
PMID- 29950070
TI - [Rheological properties of sinomenine in situ liquid crystal as liquid embolic
agent].
AB - Three different kinds of sinomenine in situ liquid crystal were prepared for
different prescriptions, to investigate the rheological properties before and
after in situ treatment and evaluate its feasibility for embolization.
Rheological experiments were carried out with cone plate fixtures. Both the
steady-state rheological and non-steady-state rheological properties of in-situ
gels and the swelling gels were studied and compared. Steady-state rheological
study results showed that all the three liquid embolic agents were non-newtonian
fluid before and after in situ treatment, which would become less ropy when they
were pressed with shear stress; their viscosities differed by 2-5 orders of
magnitude. It had a yield value of about 10 Pa before in situ treatment and about
4 500 Pa after in situ treatment. All the six systems had thixotropy while their
dynamic viscosities were not influenced by the shear rate, all less than 0.3 Pa.s
before in situ treatment more than 1 Pa.s after in situ treatment, differing by
an order of magnitude. The results of temperature sweeping showed a slight
decrease with a steady rate in viscosity within the range of 10-50 degrees C,
differing by 3-4 orders of magnitude. The results of unsteady rheology showed
that there was no obvious linear viscoelastic region in the three kinds of
agents, indicating the properties of liquid. After in situ treatment, their
linear viscoelastic range gamma<1% (No.3 was 5%), and their elastic modulus G'
was larger than the viscous modulus G", indicating the properties of solid.
Frequency scanning results showed that for the systems at low frequencies, G">G',
system viscosity in a dominant position; while at high frequencies, G'>G", system
elasticity in a dominant position. The results of compound viscosity test also
proved that the liquid embolic agent in situ can form a cubic liquid crystal (the
structure of No. 3 was destroyed after in situ treatment). The DHR-2 rheometer
was used to investigate the rheological properties of in situ gels with three
different prescriptions. The method is simple and the result is reliable, which
can provide more theoretical reference for the in vitro evaluation and practical
application of the product.
PMID- 29950071
TI - [Preparation process of norcantharidin/tetrandrine dual loaded liposomes and
their in vitro release characteristics].
AB - In order to optimize the prescription and preparation process of
norcantharidin/tetrandrine dual loaded liposomes, the dual drug loaded liposomes
were prepared by film dispersion-ultrasonic method using norcantharidin
mesoporous silica nanoparticles(MSN-NCTD)and tetrandrine(Tet). With particle size
and encapsulation efficiency as comprehensive indexes, the influences of
phospholipid cholesterol amount, ultrasonic time and ultrasonic power on
prescription process were investigated by orthogonal test; the in vitro release
characteristics of liposomes were investigated by dialysis method. The results
indicated that the best prescription process of prepared
norcantharidin/tetrandrine dual loaded liposomes was as follows: phospholipid
cholesterol ratio 2.5:1, ultrasonic time 4 min, ultrasonic power 40%; the
encapsulation efficiency was 86.62% and 79.19%respectively for NCTD and
Tet;liposomes were well-shaped under the transmission microscope, with average
particle size of (207.5+/-3.6) nm, Zeta potential of (1.345+/-0.173) mV; and the
48 h cumulative release rates of NCTD and Tet were 85.14% and 85.00%
respectively. The experiment results proved that the dual drug loaded liposomes
prepared by film dispersion-ultrasonic method had uniform particle size, high
encapsulation efficiency and in vitro sustained release characteristics.
PMID- 29950072
TI - [Comparison of integration processing technology of origin and traditional
cutting processing technology of Moslae Herba for lung-Yang deficiency rats].
AB - To compare the effect of integration processing technology of origin (IPTO) and
traditional cutting processing technology (TCPT) of Moslae Herba for lung-Yang
deficiency rats caused by complex factors, analyze the mechanism, and provide the
modern pharmacology basis for the implementation of IPTO of Moslae Herba. The rat
models of lung-Yang deficiency were established by smoking + swimming in ice
water + drinking ice water. The model rats were randomly divided into different
groups, and were treated with intragastric administration for 30 d. Then the
general signs, anal temperature and autonomic activity of the rats were observed.
The pathological morphology of lung tissues was observed, and the positive
expression of tumor necrosis factor (TNF-alpha) was observed by
immunohistochemical method, and the hematological indexes were determined. Enzyme
linked immunosorbent assay (ELISA) method was used to detect serum nitric oxide
(NO), immunoglobulin G (IGG), malondialdehyde (MDA), thromboxane B2 (TXB2) and
interleukin-8 (IL-8) level, and the organ coefficients of heart, liver, spleen,
lung, kidney and other organs were calculated. According to the results, Moslae
Herba volatile oil and decoction could improve the general signs and autonomic
activities of lung-Yang deficiency rats, improve the body weight, rectal
temperature, and the content of IGG in serum of lung-Yang deficiency rats, reduce
organ coefficients of heart, liver, spleen, lung and kidney, serum NO, MDA, TXB2,
IL-8 contents, white blood cell and TNF-alpha mean optical density in the lung
tissues of rats. witg statistically significant difference (P<0.01 or P<0.05).
The effects of IPTO volatile oil and water decoction were slightly higher.
Therefore, Moslae Herba has therapeutic effect on lung-Yang deficiency rats, and
ICPT has better effect, whose mechanism may be related to the intervention of TNF
alpha expression, improving the level of IGG, and inhibiting NO, MDA, IL-8, and
TXB2 levels.
PMID- 29950073
TI - [Standardization of preparation of rice fried Codonopsis Radix based on
correlation analysis of functional component and shape index].
AB - The quality standard of Chinese herbal medicine is the key in quality control,
and the establishment of rice processing technology standard of rice fried
Codonopsis Radix has important significance for the overall quality control. In
this study, the color brightness (L*), red-green chromaticity coordinate (a*),
yellow-blue chromaticity coordinate (b*) and total color value(E*ab)were
determined by colorimeter and used as the shape indexes. Ethanol extractives,
polysaccharide, lobetyolin and 5-hydroxymethyl furfural contents were determined
by using high performance liquid chromatography (HPLC) and ultraviolet (UV), and
used as chemical indexes in the analysis by normalization distance method. The
two index methods were adopted to optimize the processing technology of rice
fried Codonopsis Radix by taking processing temperature, processing time, rice
types and rice dosage as factors. The correlation analysis between the two index
methods was carried out by SAS 9.40 and JMP 11 software. The results showed that
all the four factors had significant differences, and the best processing
technology was as follows: polished round-grained rice as raw material,
processing temperature at 140 degrees C, processing time of 10min, and the ratio
of Codonopsis pilosula and rice is 100:30. Chemical indexes showed significant
positive correlations with shape indexes, providing basis for the quality
evaluation of rice fried Codonopsis Radix in processing.
PMID- 29950074
TI - [Triterpenoid saponins from roots of Phytolacca acinosa].
AB - A new triterpenoid saponin named esculentoside U(1), along with the five known
compounds, was isolated and characterized from the roots of Phytolacca acinosa, a
commonly used traditional Chinese medicine with anti-inflammatory and anti
rheumatoid activities. The structure of the new saponin was elucidated as 3-O
[beta-D-glucopyranosyl-(1->4)]-beta-D-xylopyranosyl]-2, 23-dihydroxyolean-11,
13(18)-diene-28, 29-dioic acid 29-methyl ester(1). The assignment of all NMR
signals of 1 was performed by means of 2D-NMR experiments.
PMID- 29950075
TI - [Two new polypeptides from extract of deer bone extract].
AB - Two new polypeptides were isolated and purified from the extract of deer bone
(constitutive part of Cucumis and Cervus polypeptide injection) by various column
chromatography including C4 300A and Sephadex G-50, as well as semipreparative
HPLC. Their N-terminal amino acid sequences were identified by De Novo sequencing
on the basis of MALDI-TOF-MS data and ExplorerTM software. The N-terminal amino
acid sequences of polypeptides were identified as NH2-Gly-Pro-Val-Gly-Pro-Thr-Gly
Pro-Val-Gly-Ala-Ala-Gly-Pro-Ser-Gly-Pro-Asp (Mei18 peptide, 1) and NH2-Ala-Gly
Pro-Ala-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Pro-Asp-Ser-Try
Asp (Mei23 peptide, 2), respectively. Mei18 and Mei 23 peptides are new
polypeptides.
PMID- 29950077
TI - [On-line scavenging activity of Huanglian by HPLC-ABTS-DAD-Q-TOF-MS].
AB - The present research aimed to establish an associated two-dimensional fingerprint
of Huanglian between characteristic chemical composition and antioxidant
activity, which was applied to on-line screen the active constituents. In this
study, the HPLC-ABTS-DAD-Q-TOF/MS method, which can simultaneously identify
individual components and rapidly screen for antioxidant compounds, was used to
screen and identify antioxidant components in Huanglian. Fourteen compositions
were discovered, and eight of them displayed antioxidant activity. The
antioxidant activity of different ingredients was evaluated by antioxidant
efficiency. The data showed that 2, 3, 4-trihydroxy phenylpropionic acid,
chlorogenic acid, ferulic acid, cularine, 3-O-feruloylquinic acid and
feruloyltyramine showed stronger antioxidant activity than that of alkaloids.
These experimental data can provide data support for the basic research of the
antioxidant ingredients of Huanglian.
PMID- 29950076
TI - [Mechanism of interaction between chrysin and leptin].
AB - The study of interaction mechanism between chrysin and leptin was investigated by
various spectroscopic techniques and atom force microscope. The ultraviolet
spectrum presents a red shift in 200-220 nm after chrysin upon. And there is a
structure alternative showed in 270 nm when the concentration ratio of chrysin
and leptin in 10-15. From the fluorescence spectrum, it was found that chrysin
could combine with leptin in physiological condition. The binding constant (Ka)
values, at 298 K and 310 K, were (0.41+/-0.05)*106 and (3.26+/-0.46)*106 L.mol-1,
and the binding site number were 1.02+/-0.04 and 0.51+/-0.01, respectively. The
atom force microscope results showed that the dimension of leptin molecules
became more swollen after binding with chrysin because of the hydrophobicity.
These results demonstrate that the mechanism of chrysin and leptin interaction
could play a role in leptin adjust in human body, and it could provide a new
aspect for the study of obesity treatment.
PMID- 29950078
TI - [Chemical fingerprinting and similarity analysis of Lonicera japonica resources].
AB - LC-MS was used to detect 41 population of Lonicera japonica from different areas.
LC-MS chemical chromatographic profile has been established. There were 23 common
peaks, seventeen of which were identified according to reference standard and
reference; SPSS software was applied to calculate the similarity of chemical
fingerprints of 41 batches and the range was from 0.99 to 0.12. On this basis,
the L. japonica's metabolites consistency was classified. Combined with
comprehensive analysis of genetic identity, we can provide a theoretical basis
for the authenticity research of Dao-di herbs and reference information for the
breeding of excellent L. japonica.
PMID- 29950079
TI - [HPLC fingerprints of pig, cattle and sheep biles].
AB - To establish the fingerprints of biles of pig, cattle and sheep, HPLC was used
with AcclaimTM RSLC 120 C18 column (3.0 mm*100 mm, 2.2 MUm, 120 A), the column
temperature 35 degrees C, acetonitrile-1% perchloric acid as mobile phase,
gradient elution, 0.5 mL.min-1 flow rate, and detection wavelength at 200 nm. The
fingerprint was generated by using Similarity Evaluation Software of
Chromatographic Fingerprint of Chinese Medicine (2004A Edition). The fingerprint
peaks were identified by reference substances and verified by ELSD and LC-MS/MS.
Then, the biles of pig, cattle and sheep were detected to contain 14, 9 and 8
common fingerprint peaks respectively, and the similarity was greater than 0.92.
To analyze each technical parameter, GHDCA in pig bile and TCA in cattle and
sheep bile were selected as reference peak. The precision, repeatability and
stability all meet the requirements of fingerprint establishment. The RSD of the
relative retention time of the fingerprint peaks was less than 1.5%, and the RSD
of the relative peak area was less than 5%. The fingerprint peaks in pig bile
were THDCA, TCDCA, GHDCA and GCDCA, and TCA, TCDCA, GCA, GCDCA and GDCA in cattle
and sheep bile. The main components of pig, cattle and sheep bile were conjugated
bile acids, but there were significant differences in bile acids between pig bile
and cattle, sheep biles. The HPLC method established in this paper is simple,
rapid and reproducible, and could be applied to the identification and quality
control of biles.
PMID- 29950080
TI - [Effect of Huangqi San on AMPK/ACC/CPT1 pathway in hyperlipidemia rats].
AB - To investigate the mechanism of the treatment of hyperlipidemia rats induced by
Huangqi San. The 40 male SD rats were randomly divided into normal group, model
group, Huangqi San low and high dose group (1, 2 g.kg-1), and positive lipitor
group (2 mg.kg-1). The normal group feeds on base feed, and other groups feed on
high-fat feed. After 8 weeks, the hyperlipidemia model was successful. After
intervention by drugs for 13 weeks, fasting blood glucose, total cholesterol,
triglycerides and LDL cholesterol content of all rats were measured. The
pathological changes of liver and skeletal muscle of rats were observed in rats.
Real-time PCR and Western blot were used to detect the mRNA and protein
expression levels of AMPK signaling pathway in the liver and skeletal muscles
(AMPK, ACC, CPT1A, SREBP2, HMGCR). The degree of FPG, TC, TG and LDL-C were the
highest in the model group, and the liver and skeletal muscle pathology were the
most obvious. After intervention by Huangqi San and lipitor, a significant
reduction in the blood sugar blood fat, liver, and skeletal muscle injury has
improved significantly, except SREBF2 and HMGCR mRNA and protein expression of
this enzyme is reduced, other AMPK pathway related mRNA and protein expression
increased significantly. Huangqi San effect is superior to lipitor. Huangqi San
may improve hyperlipidemia by regulating the AMPK signaling pathway, increasing
the oxidation of fatty acids and inhibiting cholesterol synthesis.
PMID- 29950081
TI - [Mechanisms of Fufang Danshen tablets on treating heart failure via regulating
AT1-mediated PLA2-COX2/5-LOX metabolic pathway].
AB - Myocardial fibrosis (MF) is an important pathological change involved in the
progress from myocardial infarction (MI) to heart failure(HF). Metabolic disorder
of arachidonic acid (AA) in cardiomyocytes plays an important role in process of
MF. Fufang Danshen tablets is a traditional Chinese medicine (TCM), which showed
significant effect on coronary heart diseases and anti-MF. However, the
underlying mechanism of anti-MF remains unclear. In this study, HF animal model
of myocardial infarction was established by ligation of left anterior descending
coronary artery. The heart function of rats in each group was evaluated by
echocardiography and hemodynamic measurement. Histological examination, TUNEL and
Western blot were used to detect the levels of MF and proteins related to AA
metabolism. As a result, MI significantly decreased the levels of ejection
fraction (EF), ejection fraction (FS) and left ventricular systolic pressure
(LVSP), and these decreases were significantly improved by the treatment of
Fufang Danshen tablets. Besides, Fufang Danshen tablets treatment down-regulated
the levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in
serum. HE, Masson and TUNEL staining results showed that Fufang Danshen tablets
treatment could inhibit the inflammatory cells infiltration and attenuate the
fibrosis and apoptosis to exert cardioprotective effect. Western blot indicated
that Fufang Danshen tablets treatment down-regulated the expressions of AT1,
MMP2, MM9, while up-regulated the expression of AT2 to inhibit MF. Further
mechanism study indicated that Fufang Danshen tablets inhibited MF by down
regulated the expressions of AA metabolism, such as PLA2, P450, COX2 and 5-LOX.
In summary, Fufang Danshen tablets can effectively inhibit MF in the ischemic
area after MI in rats. The mechanism is related to the regulation of AT1-mediated
PLA2-COX2 metabolic pathway.
PMID- 29950082
TI - [Calcium mobilizing effect of hawthorn leaf procyanidins in vascular endothelial
cells].
AB - The hawthorn leaves have the effect of activating blood, removing blood stasis,
regulating qi through the veins, dissolving turbidity and lowering lipid.
Procyanidinis is one of its main active components and plays an important role in
regulating vasoactivity. Previous studies showed that the regulating effect of
procyanidins was related to its regulation on nitric oxide secretion from
vascular endothelial cells, and this effect was dependent on the extracellular
calcium concentration, suggesting that the changes in intracellular calcium ion
concentration in endothelial cells may play a key role in this process. However,
the research on this issue is still insufficient so far. This study is aimed to
observe the effect of hawthorn leaf oligomeric procyanidins (HLP) on calcium
mobilization of vascular endothelial cells, and investigate the underlying
mechanism. Human umbilical vein endothelial cells (HUVEC) were cultured in vitro
and labeled with Fura-2. HUVEC were treated with HLP at concentrations of 6.25,
12.5, 25 and 50 mg.L-1, and the intracellular calcium concentrations were
measured with a living cell microscope for 30 min. HLP increased the
intracellular calcium concentration of HUVEC in a concentration dependent manner;
and the intracellular calcium concentrations in 25 and 50 mg.L-1 HLP groups were
significantly higher than that in the normal group. With the use of calcium-free
incubation buffer, addition of calcium chelating agent EGTA in incubation buffer,
or use of inhibitors for sodium calcium exchanger, the effect of HLP was
significantly inhibited. On the other hand, the effect of HLP could also be
weakened by inhibiting the calcium release from the intracellular storage. In
conclusion, these results suggest that HLP can elicit calcium mobilization in
vascular endothelial cells, which may be one of the mechanisms for its vascular
modulatory activity; and this calcium mobilizing effect may be achieved through
promoting both extracellular calcium influx and intracellular calcium release,
additionally the former may be related to activating the reverse transport of Na+
Ca2+ exchangers on the cell membrane.
PMID- 29950083
TI - [Mechanism of Acori Tatarinowii Rhizoma-Curcumae Radix treating depression based
on network pharmacology].
AB - To screen the target for the treatment of depression of Acori Tatarinowii Rhizoma
and Curcumae Radix using the pharmacological method of network pharmacology, in
order to define the mechanism of antidepressant effect. Pharmacological data
(TCMSP) of forall of chemical constituents of Acori Tatarinowii Rhizoma and
Curcumae Radix through traditional Chinese medicine system (TCMSP) was retrieved
to screen the target sites, and construct the component target PPI network.
PharmGkb database was retrieved for the genes associated with depression, and the
disease target was mapped using the Cytoscape software. The Cytoscape software
was used to merge the network and filter the core network, and further analyze
the gene GO function and the KEGG pathway enrichment. There were 62 nodes and 87
connections on the target PPI network. The PPI network had 1 289 nodes and 17 714
connections. After the network merged, the component-target-disease network had 1
337 nodes and 17 801 connections. Through screening the core network, there were
63 nodes and 935 connections, which represented the complex interaction between
the components and the target. Gene GO functional analysis suggested that
biological processes, molecular functions and cell components were involved. Gene
KEGG pathway enrichment analysis showed associations with misfolded protein,
secretory hormone secretion, and apoptosis of hippocampal neurons. The possible
mechanism for treating depression is the adjustment of wrong folding protein, sex
hormone secretion and apoptosis of hippocampal neurons.
PMID- 29950084
TI - [Effect of allicin on proliferation and apoptosis of KG-1 cells and its molecular
mechanism].
AB - Allicin is one of the main bioactive substances in garlic, with antibacterial,
hypolipidemic and other pharmacological effects. In this study, apoptosis-related
indicators were detected to explore the molecular mechanism of allicin on KG-1
cell proliferation inhibition. The apoptosis rate of KG-1 cells induced by
allicin was detected by flow cytometry. The effect of allicin on the expressions
of Bax, Bcl-2, survivin and ERK mRNA in KG-1 cells was detected by RT-qPCR.
Western blot was used to detect the expressions of caspase 3, cleaved caspase 3,
ERK1/2, p-ERK1/2 and survivin protein in KG-1 cells. According to the findings,
compared with the control group, allicin could significantly inhibit the
proliferation activity of KG-1 cells in a concentration-dependent and time
dependent manner. Flow cytometry showed that allicin could induce the apoptosis
of KG-1 cells, which was mainly late apoptosis. The results of RT-qPCR showed
that the expressions of Bax mRNA, Bcl-2, survivin and ERK mRNA in KG-1 cells
increased after treatment with allicin. The results of Western-blot showed that
after KG-1 cells were treated with allicin, the expressions of caspase 3 and its
active form cleaved caspase 3 increased, the expressions of survivin, ERK1/2 and
its active form p-ERK1/2 were decreased, of which p-ERK1/2 was down-regulated in
a dose-dependent manner. The above results suggest that allicin inhibited the
proliferation of KG-1 cells primarily by inducing late apoptosis; the execution
of apoptosis involved cleaved caspase 3; the induction of apoptosis involved the
protein expression, the decrease of ERK1/2andexpression of survivin and the dose
dependent decrease of p-ERK1/2; the mRNA expression involved the increase of Bax,
and the down-regulation of survivin, Bcl-2 and ERK1/2.
PMID- 29950085
TI - [Effect of puerarin on hypoxic pulmonary hypertension and accompanying pulmonary
fibrosi].
AB - To investigate the effect and regulatory mechanism of puerarin on pulmonary
arterial hypertension due to hypoxia and the possible accompanying pulmonary
fibrosis, The rat model of hypoxic pulmonary hypertension and the rat model of
hypoxia were established. Totally 18 clean-grade SD rats were fed and randomly
divided into normal control group, model group and hypoxia+medicine group. Each
group received intraperitoneal injection 30 min before modeling every day;
hypoxia+medicine group was injected with 20 mg.kg-1 puerarin. Normal control
group and model group were injected with the equal volume of 0.9% NaCl solution.
Normal control group was cultured under normal conditions in the laboratory,
while model group and hypoxia+medicine group were cultured in ahypoxia
environment for 21 days to observe rat hypoxic characteristics and make the
preliminary judgment about modeling. Afterwards, small animal echocardiography,
right cardiac catheterization, HE dyeing and other experiments were used to
verify the successful modeling, and puerarin has a therapeutic effect in
pulmonary hypertension caused by hypoxia in SD rats. Fluorescence quantitative
PCR, Western blot and immunofluorescence method were used to detect the changes
caused by hypoxia pulmonary fibrosis-associated protein. It was found that
puerarin could be given in anoxia to promote the expressions of CD31, VE
cadherin, inhibit the expressions of alpha-SMA, vimentin and fibronection, namely
the inhibition of vascular wall thickening. Puerarin has the therapeutic effect
on the pulmonary hypertension and accompanying pulmonary fibrosis in rats induced
by hypoxia.
PMID- 29950086
TI - [Species and medical history of "Xishuang" medicinal materials].
AB - "Xishuang" is a special phenomenon that chemical composition of medicinal
materials crystallize on the surface exposed to air for a long time. We
summarized Herbal textual research of "Xishuang" phenomenon of six herbs, such as
Schisandrae Chinensis Fructus, Moutan Cortex, Atractylodis Rhizoma, Magnoliae
Officinalis Cortex, dried persimmon frost and watermelon frost. From historical
perspective, cream of Schisandrae Chinensis Fructus was firstly discovered in Lei
Gong's Moxibustion Theory. Thereafter, dried persimmon frost was found in Song
Dynasty, which was named "white persimmon" in Ben Cao Tu Jing and had become an
independent medicine in Compendium of Materia Medica. Then, watermelon frost was
found in Yang Yi Da Quan of the Qing Dynasty, and Moutan Cortex's "sand star" was
recorded in Zeng Ding Wei Yao Tiao Bian of the Republic of China. After that,
"Xishuang" phenomenon of Atractylodis Rhizomaand Magnoliae Officinalis Cortex
were reported in 1950s and 1960s in succession. The pattern of "Xishuang" is
divided into different type, natural "Xishuang" includes Schisandrae Chinensis
Fructus, Moutan Cortex, Atractylodis Rhizoma and Magnoliae Officinalis Cortex,
artificial "Xishuang" includes watermelon frost, and dried persimmon frost formed
crystals by using artificial intervention. The above 6 kinds of herbs have
different crystal structure and chemical composition. Therefore, according to
traditional identification experience, "Xishuang" phenomenon is related to
varieties and quality of medicinal herbs. These research provide herbalism basis
for the modern study of "Xishuang" medicinal materials.
PMID- 29950087
TI - [Status and thinking of quality supervision on imported medicinal materials in
shortage].
AB - With the continuous development of traditional Chinese medicine business, the
types and amounts of Chinese materia medica resources are increasingly reduced.
By reviewing the origins, trading sources, and existing quality standards of the
available common Chinese madicinal materials in shortage, it was found that the
large amount of imported medicinal materials in domestic market or clinical
application were not due to the traditional paths such as envoys presenting
tribute, business trade, war conflict, national migration, and tourist travel,
but due to the shortage of resources in domestic origins. Meanwhile, the former
quality control standard on traditional imported medicinal materials was out of
date, and the new imported medicinal materials quality control standard was in
absence, resulting in unclear origins, unknown origins and processing methods, as
well as more and more prominent problems on mixed use of the different varieties
with same name and the same varieties from different origins. On the one hand,
this situation once again sounded the alarm for the development of Chinese
medicine industry from the resource perspective. On the other hand, the confusion
of new varieties in Chinese herbal medicine market has also brought a serious
threat to the efficacy of Chinese medicine. It is pointed out that it is an
effective way to ensure the drug safety of imported medicinal materials through
strengthening quality supervision of shortage of traditional Chinese medicines
based on the new pharmacopoeia standards.
PMID- 29950088
TI - Curved TiO2 Nanoparticles in Water: Short (Chemical) and Long (Physical) Range
Interfacial Effects.
AB - In most technological applications, nanoparticles are immersed in a liquid
environment. Understanding nanoparticles/liquid interfacial effects is extremely
relevant. This work provides a clear and detailed picture of the type of
chemistry and physics taking place at the prototypical TiO2 nanoparticles/water
interface, which is crucial in photocatalysis and photoelectrochemistry. We
present a multistep and multiscale investigation based on hybrid density
functional theory (DFT), density functional tight-binding, and quantum
mechanics/molecular mechanics calculations. We consider increasing water partial
pressure conditions from ultra-high vacuum up to the bulk water environment. We
first investigate single water molecule adsorption modes on various types of
undercoordinated sites present on a realistic curved nanoparticle (2-3 nm) and
then, by decorating all the adsorption sites, we study a full water monolayer to
identify the degree of water dissociation, the Bronsted-Lowry basicity/acidity of
the nanoparticle in water, the interface effect on crystallinity, surface energy,
and electronic properties, such as the band gap and work function. Furthermore,
we increase the water coverage by adding water multilayers up to a thickness of 1
nm and perform molecular dynamics simulations, which evidence layer structuring
and molecular orientation around the curved nanoparticle. Finally, we clarify
whether these effects arise as a consequence of the tension at the water drop
surface around the nanosphere by simulating a bulk water up to a distance of 3 nm
from the oxide surface. We prove that the nanoparticle/water interfacial effects
go rather long range since the dipole orientation of water molecules is observed
up to a distance of 5 A, whereas water structuring extends at least up to a
distance of 8 A from the surface.
PMID- 29950089
TI - Semiconductor Nanomembrane Materials for High-Performance Soft Electronic
Devices.
AB - The development of methods to synthesize and physically manipulate extremely
thin, single-crystalline inorganic semiconductor materials, so-called
nanomembranes, has led to an almost explosive growth of research worldwide into
uniquely enabled opportunities for their use in new "soft" and other
unconventional form factors for high-performance electronics. The unique
properties that nanomembranes afford, such as their flexibility and lightweight
characteristics, allow them to be integrated into electronic and optoelectronic
devices that, in turn, adopt these unique attributes. For example, nanomembrane
devices are able to make conformal contact to curvilinear surfaces and manipulate
strain to induce the self-assembly of various 3D nano/micro device architectures.
Further, thin semiconductor materials (e.g., Si-nanomembranes, transition metal
dichalcogenides, and phosphorene) are subject to the impacts of quantum and other
size-dependent effects that in turn enable the manipulation of their bandgaps and
the properties of electronic and optoelectronic devices fabricated from them. In
this Perspective, nanomembrane synthesis techniques and exemplary applications of
their use are examined. We specifically describe nanomembrane chemistry
exploiting high-performance materials, along with precise/high-throughput
techniques for their manipulation that exemplify their growing capacities to
shape outcomes in technology. Prominent challenges in the chemistry of these
materials are presented along with future directions that might guide the
development of next generation nanomembrane-based devices.
PMID- 29950090
TI - Photoreversible Molecular Motion of stpyCN Coordinated to fac-[Re(CO)3(NN)]+
Complexes.
AB - In this work, efficient trans ? cis photoswitchings of 4-(4-cyano)styrylpyridine
(stpyCN) coordinated to organometallic bipyridyl tricarbonyl rhenium(I)
complexes, fac-[Re(CO)3(NN)( trans-stpyCN)]+, where NN = 2,2'-bipyridine (bpy) or
4,4'-dimethyl-2,2'-bipyridine (dmb), are described. For both complexes, the true
trans-to- cis quantum yields determined by 1H NMR spectroscopy are similar at
313, 334, and 365 nm irradiations (Phi trans-> cistrue(313-365 nm) ~ 0.45), with
a small decrease at 404 nm (Phi trans-> cistrue(404 nm) ~ 0.37). The investigated
complexes also exhibit significant quantum yields for the reversible cis-to-
trans photoreactions (Phi cis-> trans(255 nm) = 0.22). The luminescent properties
of these complexes were also analyzed in different media to elucidate a key role
of the 3ILstpyCN state in photophysical and photochemical processes, giving new
insights on their intriguing photobehavior.
PMID- 29950092
TI - Adsorption-Desorption Behavior of Black Phosphorus Quantum Dots on Mucin Surface.
AB - Black phosphorus quantum dots (BPQDs) as novel nanomaterials have many potential
applications in biomedicine. However, the interaction of BPQDs with proteins and
their biological effects and potential risks are still unclear. Here, mucin,
which serves biologically as a physical barrier against foreign substances
entering tissues, was chosen as a model substrate for studying the adsorption
desorption behavior of BPQDs using surface plasmon resonance sensing and a quartz
crystal microbalance with dissipation monitoring. We found that the surface
modification of BPQDs with poly(ethylene glycol)-amine (PEG-NH2) reduces the
adsorption rate of the quantum dots but increases their adsorbed amount on the
mucin surface. The pH value, ionic strength, and ionic valence also had
significant effects on the adsorption behavior of BPQDs. Upon increasing the pH
from 2 to 7, the amount of BPQD adsorption decreased from 14.1 to 3.2 ng/cm2. A
high ionic strength and ionic valence (e.g., Mg2+, Al3+) also inhibit the surface
adsorption of BPQDs. Furthermore, the adsorption-desorption mechanisms of BPQDs
on the mucin surface were proposed. The adsorption-desorption behavior under
different conditions may be attributed to the steric hindrance of PEG, the
electrostatic interaction, and/or charge screening. These findings provide useful
insights into the interfacial behavior of BPQDs before they enter the tissues.
PMID- 29950091
TI - The Methanosarcina mazei MM2060 Gene Encodes a Bifunctional Kinase/Decarboxylase
Enzyme Involved in Cobamide Biosynthesis.
AB - Cobamides (Cbas) are synthesized by many archaea, but some aspects of Cba
biosynthesis in these microorganisms remain unclear. Here, we demonstrate that
open reading frame MM2060 in the archaeum Methanosarcina mazei strain Go1 encodes
a bifunctional enzyme with l-threonine- O-3-phosphate (l-Thr-P) decarboxylase (EC
4.1.1.81) and l-Thr kinase activities (EC 2.7.1.177). In Salmonella enterica,
where Cba biosynthesis has been extensively studied, the activities mentioned
above are encoded by separate genes, namely, cobD and pduX, respectively. The
activities associated with the MM2060 protein ( MmCobD) were validated in vitro
and in vivo. In vitro, MmCobD used ATP and l-Thr as substrates and generated ADP,
l-Thr-P, and ( R)-1-aminopropan-2-ol O-phosphate as products. Notably, MmCobD has
a 111-amino acid C-terminal extension of unknown function, which contains a
putative metal-binding motif. This C-terminal domain alone did not display
activity either in vivo or in vitro. Although the C-terminal MmCobD domain was
not required for l-Thr-P decarboxylase or l-Thr kinase activities in vivo, its
absence negatively affected both activities. In vitro results suggested that this
domain may have a regulatory or substrate-gating role. When purified under anoxic
conditions, MmCobD displayed Michaelis-Menten kinetics and had a 1000-fold higher
affinity for ATP and a catalytic efficiency 1300-fold higher than that of MmCobD
purified under oxic conditions. To the best of our knowledge, MmCobD is the first
example of a new class of l-Thr-P decarboxylases that also have l-Thr kinase
activity. An archaeal protein with l-Thr kinase activity had not been identified
prior to this work.
PMID- 29950093
TI - Innovative Electrochemical Screening Allows Transketolase Inhibitors to Be
Identified.
AB - Transketolases (TKs) are ubiquitous thiamine pyrophosphate (TPP)-dependent
enzymes of the nonoxidative branch of the pentose phosphate pathway. They are
considered as interesting therapeutic targets in numerous diseases and infections
(e.g., cancer, tuberculosis, malaria), for which it is important to find specific
and efficient inhibitors. Current TK assays require important amounts of enzyme,
are time-consuming, and are not specific. Here, we report a new high throughput
electrochemical assay based on the oxidative trapping of the TK-TPP intermediate.
After electrode characterization, the enzyme loading, electrochemical protocol,
and substrate concentration were optimized. Finally, 96 electrochemical assays
could be performed in parallel in only 7 min, which allows a rapid screening of
TK inhibitors. Then, 1360 molecules of an in-house chemical library were screened
and one early lead compound was identified to inhibit TK from E. coli with an
IC50 of 63 MUM and an inhibition constant ( KI) of 3.4 MUM. The electrochemical
assay was also used to propose an inhibition mechanism.
PMID- 29950094
TI - Tailored Network Formation in Graphene Oxide Gels.
AB - Graphene oxide (GO)-based gels are attractive because of their ability to retain
individual nanosheet properties in a three-dimensional (3D) bulk material. The
final morphology and properties of these 3D gel networks depend strongly on the
type and density of cross-links, and these gels can be dried and annealed to form
aerogels with both high conductivity (560 S/m) and high surface area (1700 m2/g).
The results show that both ammonia content and the parent nanosheet morphology
(crumpled vs flat) have a strong influence on the cross-linked structure and
composition; notably, nitrogen is found in the gels, suggesting that ammonia
actively participates in the reaction rather than as a mere catalyst. The GO
nanosheet morphology may be altered using spray-drying to obtain crumpled GO
(cGO) nanosheets and form cGO gels; this allows for an additional handle in the
creation of GO-based gels with tunable density, electrical conductivity, and
surface area.
PMID- 29950095
TI - Rheological Characterization of Mixed Surfactant Films at Droplet Interfaces via
Micropipette Aspiration.
AB - Cationic and anionic surfactant mixtures can form viscous films that dominate the
rheology and stability of micrometer-sized droplet suspensions. In this work, we
use micropipette aspiration to study the mechanical properties of mixed
surfactant surface films of anionic sodium dodecyl sulfate (SDS) and cationic
dodecylamine hydrochloride (DAH) on alkane and lipid droplets. For octane
droplets, SDS was found to decrease the surface tension until a minimum of 5 +/-
1 mJ/m2 was reached after the critical micelle concentration (cmc). The surface
viscosity of the droplets was found to be on the order of 10-3 mN s/m at an SDS
concentration of 10 mM. An addition of 0.2 mM of DAH was found to increase this
viscosity to a peak of 0.24 +/- 0.01 mN s/m. Similar to octane, the surface
tension of dodecane decreased to a value of 7.7 +/- 0.4 mJ/m2 at SDS
concentrations above cmc. Unlike with octane, however, the dodecane droplets had
a significant surface viscosity of 0.37 +/- 0.01 mN s/m when only the 10 mM SDS
film was present. An addition of DAH caused a decrease in this viscosity
initially, before rising to a peak viscosity of 0.45 +/- 0.01 mN s/m at a DAH
concentration of 0.15 mM. We speculate that the peaks in viscosities were the
result of the completions of a phase change associated with microcrystalline
SDS/DAH grains growing in the film at the surface of the droplets. Fluorescence
microscopy and visual observations provided further evidence that these films can
show rigid microcrystalline-like structure. Further work done with soybean oil in
the same conditions and with a lipid film, simulating biological lipid droplets,
confirmed that lipid droplets behave rheologically similar to alkanes in the
presence of these mixed surfactant and lipid films. These results imply that
droplet mechanics may be heavily influenced by the presence of microcrystalline
grains in the oil-water systems with complex surfactant mixtures.
PMID- 29950096
TI - Small Saccharides as a Blanket around Proteins: A Computational Study.
AB - Saccharides stabilize proteins exposed to thermal fluctuations and stresses.
While the effect of a layer of trehalose around a protein on the melting
temperature has been well studied, its role as a thermal insulator remains
unclear. We report calculations of thermalization in small saccharides, including
glucose, galactose, lactose, and trehalose, and thermal transport through a
trehalose layer between water and protein and between gold, such as a gold
nanoparticle, and its cellular environment. The thermalization rates calculated
for the saccharides provide information about the scope of applicability of
approaches that can be used to predict thermal conduction in these systems,
specifically where Fourier's law breaks down and where a Landauer approach is
suitable. We find that trehalose serves as an excellent molecular insulator over
a wide range of temperatures.
PMID- 29950097
TI - Single-Atom-Based Vanadium Oxide Catalysts Supported on Metal-Organic Frameworks:
Selective Alcohol Oxidation and Structure-Activity Relationship.
AB - We report the syntheses, structures, and oxidation catalytic activities of a
single-atom-based vanadium oxide incorporated in two highly crystalline MOFs, Hf
MOF-808 and Zr-NU-1000. These vanadium catalysts were introduced by a
postsynthetic metalation, and the resulting materials (Hf-MOF-808-V and Zr-NU
1000-V) were thoroughly characterized through a combination of analytic and
spectroscopic techniques including single-crystal X-ray crystallography. Their
catalytic properties were investigated using the oxidation of 4-methoxybenzyl
alcohol under an oxygen atmosphere as a model reaction. Crystallographic and
variable-temperature spectroscopic studies revealed that the incorporated
vanadium in Hf-MOF-808-V changes position with heat, which led to improved
catalytic activity.
PMID- 29950098
TI - Depth-Resolved Characterization of Perylenediimide Side-Chain Polymer Thin Film
Structure Using Grazing-Incidence Wide-Angle X-ray Diffraction with Tender X
rays.
AB - Polymers with a perylenediimide (PDI) side chain (PAc12PDI) consist of two kinds
of crystalline structures with various types of orientations in a thin film.
Understanding the population of the microcrystalline structure and its
orientation along the thickness is strongly desired. Grazing-incidence wide-angle
X-ray diffraction (GIWAXD) measurements with hard X-rays, which are generally
chosen as lambda = 0.1 nm, are a powerful tool to evaluate the molecular
aggregation structure in thin films. A depth-resolved analysis for the outermost
surface of the polymeric materials using conventional GIWAXD measurements,
however, has limitations on depth resolution because the X-ray penetration depth
dramatically increases above the critical angle. Meanwhile, tender X-rays (lambda
= 0.5 nm) have the potential advantage that the penetration depth gradually
increases above the critical angle, leading to precise characterization for the
population of crystallite distribution along the thickness. The population of the
microcrystalline states in the PAc12PDI thin film was precisely characterized
utilizing GIWAXD measurements using tender X-rays. The outermost surface of the
PAc12PDI thin film is occupied by a monoclinic lattice with a = 2.38 nm, b = 0.74
nm, c = 5.98 nm, and beta = 108.13 degrees , while maintaining the c-axis
perpendicular to the substrate surface. Additionally, the presence of solid
substrate controls the formation of the crystallite with unidirectional
orientation.
PMID- 29950099
TI - Alternative Method to Detect Neuronal Degeneration and Amyloid beta Accumulation
in Free-Floating Brain Sections With Fluoro-Jade.
AB - Fluoro-Jade is a fluorescein-derived fluorochrome which specifically binds to
damaged neurons. Due to this characteristic, it is commonly used for the
histochemical detection and quantification of neurodegeneration in mounted brain
sections. Here, we describe an alternative and simpler histochemistry protocol
based on the use of free-floating brain sections. For this purpose, we have used
brain slices from wild-type and 5xFAD mice as well as from mice that received an
intracerebral injection of oligomeric amyloid beta peptides. We observed that our
histochemistry staining procedure allows for a well-defined labeling of
degenerating neurons providing a better signal-to-noise ratio staining than the
commonly used one. In addition, our modified protocol demonstrates the ability of
Fluoro-Jade C to also fluorescently label amyloid beta plaques.
PMID- 29950100
TI - Food Insecurity and Psychological Distress Among Former and Current Smokers With
Low Income.
AB - PURPOSE: To examine how food insecurity and psychological distress interact in
its association with smoking and to explore how food insecurity and psychological
distress are associated with quitting smoking using quit ratio estimates. DESIGN:
Cross-sectional study. SETTING: Data from the 2015 California Health Interview
Survey. PARTICIPANTS: A total of 3007 lower income adults who have ever smoked.
MEASURES: Ever smoking was defined as smoking 100+ cigarettes in the entire
lifetime, with current smoking defined as smoking "every day" or "some days" and
former smoking defined as smoking "not at all." Psychological distress and food
insecurity were measured by the 6-item K6 Psychological Distress Scale and the 6
item Food Security Survey Short Form, respectively. ANALYSIS: Multiple logistic
regression analysis was used to examine correlates of smoking status. Quit ratios
(percentage of ever smokers who have quit) were calculated across study
variables. RESULTS: Reporting food insecurity with psychological distress was
independently associated with lower odds of being a former smoker, compared to
reporting food security without psychological distress. The quit ratio was lower
among ever smokers reporting food insecurity with distress (41%) compared to ever
smokers reporting food security without distress (63%). CONCLUSIONS: Specific
conditions of impoverishment, such as food insecurity, interact with
psychological distress in its association with continued smoking. Interventions
to reduce socioeconomic disparities in smoking should consider the interacting
role of food insecurity and psychological distress.
PMID- 29950101
TI - Prenatal and perinatal risk factors and the clinical implications on autism
spectrum disorder.
AB - Prenatal and perinatal factors may increase the risk of autism spectrum disorder.
However, little is known about whether unaffected siblings of probands with
autism spectrum disorder also share the phenomenon and whether the
prenatal/perinatal factors are related to the clinical severity of autistic
symptoms. We compared the frequency of prenatal and perinatal factors among 323
probands with autism spectrum disorder (mean age +/- standard deviation, 10.7 +/-
3.5 years; males, 91.0%), 257 unaffected siblings (11.7 +/- 4.5; 42.8%), and 1504
typically developing controls (8.9 +/- 1.6 years; 53.1%); and investigated their
effects on the severity of autistic symptoms. We found that probands with autism
spectrum disorder and their unaffected siblings had more prenatal/perinatal
events than typically developing controls with higher numbers of
prenatal/perinatal factors in probands than in unaffected siblings. The
prenatal/perinatal events were associated with greater stereotyped behaviors,
social-emotional problems, socio-communication deficits, and overall severity. We
also found that six prenatal/perinatal factors (i.e. preeclampsia,
polyhydramnios, oligoamnios, placenta previa, umbilical cord knot, and
gestational diabetes) were associated with the severity of autistic symptoms,
particularly stereotyped behaviors and socio-communication deficits. Our findings
suggest that prenatal and perinatal factors may potentially moderate the clinical
expression of autism spectrum disorder. The underlying mechanism warrants further
research.
PMID- 29950102
TI - Development of a Multidimensional Measure to Examine Fear of Dementia.
AB - Persons with and without a family history of dementia report concerns for
developing this syndrome; yet, less is known about the specific aspects of
dementia that are feared. The Fear of Dementia (FOD) scale was created to assess
these concerns. This study examined the psychometric properties of the FOD scale
using a sample of middle-aged and older adults ( N = 734). We then explored the
factor structure of the scale 2 years later using a smaller sample from the first
study ( N = 226). Three factors emerged, highlighting several main areas of
concern: Burden and Loss, Quality of Life, and Perceived Social and Cognitive
Loss. Preliminary data suggest that the FOD scale is a reliable and valid
instrument for assessing the multidimensional nature of the concern about
developing dementia. Attention to what specifically is feared may help further
our understanding of health behaviors, coping, and targeted supports.
PMID- 29950103
TI - Positive outcome expectancy mediates the relationship between social influence
and Internet addiction among senior high-school students.
AB - Background and aims Based on the foundations of Bandura's social cognitive theory
and theory of triadic influence (TTI) theoretical framework, this study was
designed to examine the mediating role of positive outcome expectancy of Internet
use in the relationship between social influence and Internet addiction (IA) in a
large representative sample of senior high-school students in Taiwan. Methods
Using a cross-sectional design, 1,922 participants were recruited from senior
high schools throughout Taiwan using both stratified and cluster sampling, and a
comprehensive survey was administered. Results Structural equation modeling and
bootstrap analyses results showed that IA severity was significantly and
positively predicted by social influence, and fully mediated through positive
outcome expectancy of Internet use. Discussion and conclusions The results not
only support Bandura's social cognitive theory and TTI framework, but can also
serve as a reference to help educational agencies and mental health organizations
design programs and create policies that will help in the prevention of IA among
adolescents.
PMID- 29950104
TI - Playing the wrong game again? Policy responses to problematic video gaming in
Brazil.
AB - Brazil is the leading game market in South America and the second leading market
in Latin America. Worldwide, Brazil ranks fourth in number of gamers, with nearly
66.3 million gamers. In the last years, there has been a significant and
progressive concern about the negative consequences of video gaming overuse, but
no population-based study has estimated the prevalence of problematic gaming in
Brazil. There is also no public policy aimed at reducing risk and harm of
problematic gaming. Drawing a parallel between gaming and alcohol policies, we
discuss some alternatives to address this challenging situation.
PMID- 29950106
TI - Condom use intentions mediate the relationships between psychosocial constructs
and HIV sexual risk behavior in young Black men who have sex with men.
AB - HIV prevention interventions that reduce sexual risk behaviors among young Black
men who have sex with men (YBMSM), the most severely affected population in the
United States, are critical for reducing disparities in HIV infection. However,
there are few theory-based sexual risk reduction interventions designed
specifically for YBMSM. This study tested the applicability of the Integrated
Behavioral Model (IBM), which theorizes that behavioral intentions mediate the
relationship between psychosocial constructs and health behavior on condomless
anal intercourse (CAI) among YBMSM. To test key constructs of the IBM, analyses
were conducted with baseline data from the HealthMpowerment (HMP) randomized
controlled trial. Logistic regression was used to examine the relationships
between condom use self-efficacy, norms, attitudes, intentions, and environmental
constraints, and CAI. Mediation analysis was conducted to determine if condom use
intentions mediated the relationship between psychosocial constructs (i.e.,
condom use self-efficacy, norms, and attitudes) and CAI. Overall 55.7% reported
one or more acts of CAI with a male partner in the past 3 months. Those who
reported CAI in the 3 months prior to the baseline survey reported lower self
efficacy for condom use, lower condom use norms, more negative attitudes toward
condom use, and lower condom use intentions at baseline than those who reported
no CAI. In mediation analysis, the relationships between CAI and self-efficacy
for condom use (estimated indirect effect = -0.004 (SE = 0.002)), condom use
norms (-0.002 (SE = 0.001)) and attitudes toward condom use (-0.005 (SE = 0.002))
were mediated by condom use intentions. This study applied the IBM to sexual risk
behavior among a sample of YBMSM. Results indicate that the relationships between
condom use self-efficacy, norms, and attitudes, and CAI were mediated by condom
use intentions. Future theory-informed interventions should focus on increasing
self-efficacy for condom use, condom use norms, attitudes toward condom use, and
condom use intentions to reduce CAI among YBMSM.
PMID- 29950105
TI - Caregiver perceptions of environment moderate relationship between neighborhood
characteristics and language skills among youth living with perinatal HIV and
uninfected youth exposed to HIV in New York City.
AB - Despite the increased recognition of how neighborhood conditions bear on
cognitive and academic outcomes, no studies have examined the influences of
objective and subjective neighborhood indices on specific areas of cognitive
functioning among youth living with perinatal HIV (PHIV). In the United States
(US), this is of particular concern as HIV has disproportionately affected
African American youth living in economically disadvantaged and racially
segregated communities. Thus, based on a longitudinal cohort study of
psychosocial and behavioral health outcomes in 340 perinatally HIV-exposed but
uninfected (PHEU) and PHIV youth residing in New York City, ages 9-16 years at
enrollment, we analyzed data from baseline and multiple follow-up (FU)
quantitative interviews with youth and their primary caregivers, from when they
were at least 13-years-old (approximately 4-6 years post enrollment). We examined
the association between baseline neighborhood indices (2000 US census data and
caregiver's perception of neighborhood stressors) and youth receptive language
skills (PPVT; Peabody Picture Vocabulary Test) at FU2 and FU3. Census data
(percentage of families in neighborhood living below the national poverty rate,
median neighborhood household income, and percentage of residents professionally
employed) were not independently associated with PPVT scores at both follow-ups.
However, in the logistic regression model, the more caregivers perceived their
neighborhood as stressful and subjected to violence, the stronger the
relationship between census data indicators of low resource neighborhoods and
lower PPVT scores for both groups. Findings support "place-based" policies and
practices that alleviate caregiver experiences of neighborhood stressors which
may contribute to improved cognitive outcomes for youth living with and affected
by PHIV.
PMID- 29950107
TI - Antipsychotic Drug-Induced Movement Disorders: A Forgotten Problem?
PMID- 29950108
TI - Implementation and assessment of a model to increase HIV testing among men who
have sex with men and transgender women in Thailand, 2011-2016.
AB - HIV testing among men who have sex with men (MSM) and transgender (TG) women
remains low in Thailand. The HIV prevention program (PREV) to increase HIV
testing and link those who tested HIV-positive to care provided trainings to peer
educators to conduct target mapping, identify high risk MSM and TG women through
outreach education and offer them rapid HIV testing. Trained hospital staff
provided HIV testing and counseling with same-day results at hospitals and mobile
clinics and referred HIV-positive participants for care and treatment. We used a
standardized HIV pre-test counseling form to collect participant characteristics
and analyzed HIV test results using Poisson regression and Wilcoxon rank sum
trend tests to determine trends over time. We calculated HIV incidence using data
from participants who initially tested HIV-negative and tested at least one more
time during the program. Confidence intervals for HIV incidence rates were
calculated using the Exact Poisson method. From September 2011 through August
2016, 5,629 participants had an HIV test; their median age was 24 years, 1,923
(34%) tested at mobile clinics, 5,609 (99.6%) received their test result, and
1,193 (21%) tested HIV positive. The number of people testing increased from 458
in 2012 to 1,832 in 2016 (p < 0.001). Participants testing at mobile clinics were
younger (p < 0.001) and more likely to be testing for the first time (p < 0.001)
than those tested at hospitals. Of 1,193 HIV-positive participants, 756 (63%) had
CD4 testing. Among 925 participants who returned for HIV testing, HIV incidence
was 6.2 per 100 person-years. Incidence was highest among people 20-24 years old
(10.9 per 100 person-years). HIV testing among MSM and TG women increased during
the PREV program. HIV incidence remains alarmingly high especially among young
participants. There is an urgent need to expand HIV prevention services to MSM
and TG women in Thailand.
PMID- 29950109
TI - A pilot evaluation of 'Working Out Dads': promoting father mental health and
parental self-efficacy.
AB - AIM: Approximately one in 10 fathers experience mental health difficulties in the
early years of parenting, yet there is a dearth of evidence-based interventions
to promote fathers' mental health at this time. Therefore, the aims of this study
were: (1) to obtain preliminary data on the short-term changes in mental health
symptoms and parenting self-efficacy for fathers of young children (aged 0-4
years) participating in Working Out Dads (WOD) and (2) to explore fathers'
experiences of participation in WOD. METHOD: The sample consisted of 57 fathers
who had at least one child aged between 0 and 4 years. Participants completed pre
and post- measures to assess the severity of depressive, anxiety and stress
symptoms and parenting self-efficacy. A brief survey of fathers' experiences in
WOD was also completed. RESULTS: There was a significant reduction in fathers'
reports of depressive and stress symptoms from pre- to post-intervention, and no
significant change in anxiety symptoms. Parenting self-efficacy significantly
increased from pre- to post-intervention. All changes were associated with
moderate to large effect sizes. Fathers indicated that they were satisfied with
the programme and that they were more confident in managing the stress of
parenting and in their overall role as a father. CONCLUSIONS: This is the first
study to evaluate WOD and provides promising preliminary evidence for its short
term effects on fathers' mental health and parenting self-efficacy. Pilot results
are positive and are a critical first step, informing the design of a more robust
evaluation in the future.
PMID- 29950110
TI - The value of CT findings for prognostic prediction of spontaneous superior
mesenteric artery dissection.
AB - Background Spontaneous superior mesenteric artery (SMA) dissection is rare cause
of acute abdomen. Time-dependent change of SMA dissection has not been
established. Purpose To determine Sakamoto classification (SC) type of acute and
chronic SMA dissection (aSMAD and cSMAD) to predict the treatment methods and
outcome. Material and Methods From April 2003 to March 2017, unenhanced and
contrast-enhanced CT were used to diagnose acute symptomatic or chronic
asymptomatic SMA dissection in 25 consecutive patients without aortic dissection.
Correlations between SCs and treatment methods and outcomes were investigated.
Results All 13 patients with aSMAD initially received conservative treatment.
Initial SCs in aSMAD were type I = 1, type III = 9, and type IV = 3. Three of
nine initial type III and two of three initial type IV changed to type I at
follow-up. One of nine type III changed to type II at follow-up. Ohers did not
change. One with initial type III required vascular repair, so the final SC was
not available. Three patients required bowel resection. In cSMAD of 12 patients,
the initial/final SC were type I and IV in ten and two patients, respectively,
without change during follow-up. cSMAD was significantly older than aSMAD. The
initial length of dissection of aSMAD was longer than in the cSMAD group. In
aSMAD, the final length of dissection was significantly shorter than in the
initial computed tomography scan. Conclusion Initial SC differed significantly
between aSMAD and cSMAD. Initial SC types in aSMAD were type III and IV mainly,
and changed during the observation period. In cSMAD, SC types were I and IV
without change.
PMID- 29950111
TI - Clinical routine use of virtual monochromatic datasets based on spectral CT in
patients with hypervascularized abdominal tumors - evaluation of effectiveness
and efficiency.
AB - Background Virtual monochromatic images (VMI) generated using spectral computed
tomography (CT) are promising recently available tools to improve diagnostic
performance in oncologic patients. Purpose To investigate if virtual
monochromatic datasets are suitable for clinical routine use in patients with
hypervascularized abdominal tumors. Material and Methods A total of 41 patients
with hypervascularized hepatocellular carcinoma (HCC), renal cell carcinoma
(RCC), or neuroendocrine tumors (NET) were enrolled in the study; 451 CT series
were analyzed. In an intra-individual study design, virtual monochromatic
datasets of the arterial phase of each scan were computed. Image quality was
assessed objectively by determining signal-to-noise ratio (SNR) and contrast-to
noise ratios (CNR) and subjectively by using five-point Likert-scales. The volume
CT dose index (CTDIvol) was taken from each radiation dose report. The increase
in reading time was estimated from the increase in the number of images. Results
Intra-individual comparison of the spectral mode in the arterial phase with the
portal venous phase revealed no significant increase in the applied dose. SNR,
CNRtumor-to-liver , and CNRtumor-to-muscle were significantly increased by
lowering virtual monochromatic energy. Subjective image quality scores revealed
an increase of contrast in low energy datasets, resulting in significantly higher
diagnostic confidence, but an increased image noise at low energies. While
diagnostic confidence improved, taking all datasets into account resulted in a
significantly longer estimated reading time. Conclusion In clinical practice, the
use of low energy VMI improved diagnostic confidence without a significant
increase in dose. The main disadvantage is a decrease in efficiency due to longer
reading times.
PMID- 29950112
TI - From culture to the brain.
PMID- 29950113
TI - The Psychiatry Ashes Test: July update.
PMID- 29950115
TI - Swim training affects bone canonical Wnt pathway in type 2 diabetes induced by
high fat diet and low dose of streptozotocin in male rats.
AB - OBJECTIVE: Susceptibility to diabetes-induced bone complication has been linked
to Wnt signaling, which plays an important role in bone development and
remodeling. In this study, the effect of swim training on Wnt pathway in T2DM was
investigated. MATERIALS AND METHODS: Forty male rats were assigned to groups:
control (C), diabetic (D), exercised control (E) and diabetic exercised (DE). One
week after the induction of diabetes, animals were subjected to swim. At the end
of training, bone gene and protein levels of SOST, RUNX2 and RANKL/OPG ratio were
measured. RESULTS: Diabetes could significantly increase bone sclerostin
expression levels, while decreased RUNX2 mRNA and protein. Bone RANKL/OPG ratio
was significantly lower in diabetic rats compared to control group. Swim training
significantly increased this ratio in DE compared to D group. CONCLUSION: Swim
training could partially compensate the diabetes-associated changes of Wnt
pathway possibly by moderating sclerostin or blood sugar.
PMID- 29950114
TI - Mothers of children with autism spectrum disorders: Play behaviors with infant
siblings and social responsiveness.
AB - Mother-infant interactions are a proximal process in early development and may be
especially salient for children who are at risk for social difficulties (i.e.
infant siblings of children with autism spectrum disorder). To inform how indices
of maternal behaviors may improve parent-mediated interventions designed to
mitigate autism spectrum disorder risk, the present study explored maternal
social responsiveness ratings and social behaviors during dyadic play
interactions. Dyads were recruited from families with at least one older child
with autism spectrum disorder (high-risk group, n = 90) or families with no
history of autism spectrum disorder (low-risk group, n = 62). As part of a
prospective study, interactions were coded when infant siblings were 6, 9, and 12
months of age, for gaze, affect, vocalizations, and multimodal bids or responses
(i.e. social smiles). Maternal social responsiveness was indexed via the Social
Responsiveness Scale. Mothers in both risk groups had comparable Social
Responsiveness Scale scores and social behaviors during play. Two maternal
behaviors emerged as positive correlates of infant social behaviors and are thus
of high relevance to parent-mediated interventions. Specifically, more maternal
positive affect and the use of multimodal bids or responses were associated with
more infant positive affect, vocalizations, gaze to face, and multimodal bids or
responses.
PMID- 29950116
TI - MSDC-0602K, a metabolic modulator directed at the core pathology of non-alcoholic
steatohepatitis.
AB - INTRODUCTION: Non-alcoholic steatohepatitis (NASH) is a serious form of non
alcoholic fatty liver disease (NAFLD) for which there is no marketed treatments.
NAFLD is initiated by excess intake of nutrients and recent evidence has
pinpointed the mitochondrial pyruvate carrier (MPC) as a mediator of the
nutritional overload signals. Areas covered: An overview is given of MSDC-0602K,
a new agent in development that modulates the MPC and as such treats the symptoms
of fatty liver including dysfunctional lipid metabolism, inflammation, and
insulin resistance as well as the key liver pathology including fibrosis.
METHODOLOGY: The current evaluation is written from the direct experience of the
authors and review of published literature using standard search techniques.
Expert Opinion: The mechanism of action of MSDC-0602K appears to be suited for
treatment of the NASH pathophysiology. An ongoing phase 2b dose-ranging trial
should demonstrate whether or not MSDC-0602K has the potential to be a
cornerstone metabolic therapy for the treatment of NASH.
PMID- 29950117
TI - Emerging patents in the therapeutic areas of glioma and glioblastoma.
AB - INTRODUCTION: Glioblastoma multiforme (GBM) is the most common and aggressive
malignant glioma, with patients having a median survival of just over one year.
Current chemotherapies, with surgery and radiotherapy, provide only minor patient
benefit. There is a great need to discover and develop novel therapies for this
devastating disease. Areas covered: The patent literature reveals novel
therapies, providing insights into emerging GBM therapeutics. We have used the
Google and USPTO patent databases to generate a detailed landscape of patents and
patent applications from companies active in the areas of glioma and/or GBM.
Specific patents have been grouped into six areas: novel compounds; treatments
and therapeutic targets; combination therapies; immunotherapies; delivery
methods; and biomarkers for diagnosis and prognosis. Expert opinion: There has
been a steady increase in the number of patents on GBM over the last five years.
Despite many new compounds being developed and patented for a broad range of
cancers, only a small percentage of these are specifically targeted to GBM.
Notable trends in the patent literature include both the development of
combination therapies to combat the heterogeneous nature of GBM, and the use of
immunotherapies building on the promise of cancer vaccines and CAR T-cell
therapy.
PMID- 29950118
TI - Evidence of increased humoral endocrine organ-specific autoimmunity in severe and
classic X-chromosome aneuploidies in comparison with 46,XY control subjects.
AB - OBJECTIVE: In literature, the importance of X-linked gene dosage as a
contributing factor for autoimmune diseases is generally assumed. However, little
information is available on the frequency of humoral endocrine organ-specific
autoimmunity in X-chromosome aneuploidies. In our preliminary study, we
investigated the endocrine organ-specific humoral autoimmunity relative to four
different organ-specific autoimmune diseases in a group of adult 47,XXY KS
patients and in adults 46,XY control males (type 1 diabetes, T1DM; Addison's
disease, AD; Hashimoto thyroiditis, HT; autoimmune chronic atrophic gastritis,
AG). The aim of the present study is to evaluate the frequency of autoantibodies
(Abs) specific for T1DM, AD, HT, and AG in rarer higher grade X-chromosome
aneuploidies (HGA) and in 47,XXY children. DESIGN AND METHODS: Samples from 192
Caucasian patients with an X-chromosome aneuploidy (176 patients (55 children,
121 adults) with 47,XXY karyotype (KS patients) and 16 HGA patients (eight
children, eight adults)) recruited from Sapienza, University of Rome (2007-2017)
were tested for Abs specific for T1DM (insulin-Abs, GAD-Abs, IA-2-Abs, Znt8-Abs),
HT (TPO-Abs), AD (21-OH-Abs), and AG (APC-Abs). The results were compared to
those found in 213 46,XY control subjects (96 children, 117 adults). RESULTS:
Altogether humoral organ-specific immunoreactivity was found in 13% of KS and HGA
patients, with a significantly higher frequency than in the controls (p=.008).
Almost 19% of HGA patients were positive for at least one of the organ-specific
Abs investigated compared to 12.5% of KS patients. The frequency of the overall
immunoreactivity was higher in KS children than in KS adults. The frequency of
diabetes-specific Abs was significantly higher in the patient cohort than in
controls (p=.005). Thyroid- and gastric-specific autoimmunity was also found in
KS and HGA patients, while adrenal-specific immunoreactivity was rare.
CONCLUSIONS: These results suggest for the first time that the risk of endocrine
organ-specific humoral autoimmunity progressively increases with the severity of
X-chromosome polisomy. The screening for diabetes-, thyroid-, and gastric
specific autoimmunity should be considered in clinical practice for identifying
rare and classic X-chromosome aneuploid patients at risk of developing organ
specific autoimmune diseases.
PMID- 29950119
TI - Insulin/IGF-1 enhances intestinal epithelial crypt proliferation through
PI3K/Akt, and not ERK signaling in obese humans.
AB - The intestinal epithelium is continuously regenerated through proliferation and
differentiation of stem cells located in the intestinal crypts. Obesity affects
this process and results in greater stem cell proliferation and altered tissue
growth and function. Obesity-induced high levels of insulin and insulin-like
growth factor-1 in the stem cell niche are found to impact proliferation in
rodents indicating that insulin and insulin-like growth factor-1 receptors may
play a role in modulating intestinal epithelial stem cell proliferation. To
determine whether insulin or insulin-like growth factor-1 can induce
proliferation in human intestinal epithelial stem cells, and if two downstream
insulin and insulin-like growth factor-1 receptor signaling pathways, PI3K/Akt
and ERK, are involved, we used primary small intestinal epithelial crypts
isolated from obese humans and investigated (1) the effect of insulin or insulin
like growth factor-1 on crypt proliferation, and (2) the effect of insulin and
insulin-like growth factor-1 signaling inhibitors on insulin or insulin-like
growth factor-1-induced proliferation. We found that insulin and insulin-like
growth factor-1 enhanced the proliferation of crypt cells, including intestinal
epithelial stem cells. Inhibition of the PI3K/Akt pathway attenuated insulin and
insulin-like growth factor-1-induced proliferation, but inhibition of the ERK
pathway had no effect. These results suggest that the classical metabolic PI3K
pathway and not the canonical proliferation ERK pathway is involved in the
insulin/insulin-like growth factor-1-induced increase in crypt proliferation in
obese humans, which may contribute to abnormal tissue renewal and function.
Impact statement This study investigates if insulin or insulin-like growth factor
1 (IGF-1) induces intestinal epithelial proliferation in humans, and if insulin
and IGF-1 receptor signaling is involved in this process in obesity. Although
obesity-induced high levels of insulin and IGF-1 in the stem cell niche are found
to impact the proliferation of intestinal epithelial stem cells in rodents, we
are the first to investigate this effect in humans. We found that insulin and IGF
1 enhanced the proliferation of intestinal crypts (including stem cells and other
crypt cells) isolated from obese humans, and PI3K/Akt, and not ERK signaling was
involved in insulin or IGF-1-induced proliferation. The imbalance in signaling
between PI3K/Akt and ERK pathways may point to a pathway-specific impairment in
insulin/IGF-1 receptor signaling. We propose that this may contribute to
reciprocal relationships between insulin/IGF-1 receptor resistance and intestinal
epithelial proliferation that leads to abnormal tissue renewal and function.
PMID- 29950120
TI - Polycyclic aromatic hydrocarbons exposure and early miscarriage in women
undergoing in vitro fertilization-embryo transfer.
AB - Various factors have been reported to be associated with early miscarriages,
including microbial infection, chemical toxicity, maternal disorders and genetic
abnormalities. In the present study, a prospective cohort study was conducted to
investigate whether urinary concentrations of hydroxylated polycyclic aromatic
hydrocarbons (OH-PAHs) were associated with early pregnancy loss in women
undergoing in vitro fertilization-embryo transfer (IVF-ET). Risk of spontaneous
pregnancy loss in patients exposed to PAHs was analysed using 40 patients who had
experienced early pregnancy loss compared to 40 who had normal live births.
Single spot morning urine samples were collected from each patient 30 days after
embryo transfer when clinical pregnancy was confirmed and ten urinary OH-PAHs
were measured. After adjustment for age and BMI using a Log Binomial Model, only
2 + 3-PHE was found to be associated positively with early miscarriage. Using
Receiver Operating Characteristic (ROC) curve analysis, the Area Under the Curve
(AUC) was 0.78 (p<0.001), suggesting that 2 + 3-PHE might provide a potential
biomarker to predict the miscarriage risk in patients exposed to high level of
PAHs.
PMID- 29950121
TI - Foot and mouth disease vaccine strain selection: current approaches and future
perspectives.
AB - INTRODUCTION: Lack of cross protection between foot and mouth disease (FMD) virus
(FMDV) serotypes as well as incomplete protection between some subtypes of FMDV
affect the application of vaccine in the field. Further, the emergence of new
variant FMD viruses periodically makes the existing vaccine inefficient.
Consequently, periodical vaccine strain selection either by in vivo methods or in
vitro methods become an essential requirement to enable utilization of
appropriate and efficient vaccines. Areas covered: Here we describe the cross
reactivity of the existing vaccines with the global pool of circulating viruses
and the putative selected vaccine strains for targeting protection against the
two major circulating serotype O and A FMD viruses for East Africa, the Middle
East, South Asia and South East Asia. Expert commentary: Although in vivo cross
protection studies are more appropriate methods for vaccine matching and
selection than in vitro neutralization test or ELISA, in the face of an outbreak
both in vivo and in vitro methods of vaccine matching are not easy, and time
consuming. The FMDV capsid contains all the immunogenic epitopes, and therefore
vaccine strain prediction models using both capsid sequence and serology data
will likely replace existing tools in the future.
PMID- 29950122
TI - Update on the prevalence and determinants of folic acid use in Japan evaluated
with 91,538 pregnant women: the Japan Environment and Children's Study.
AB - OBJECTIVE: To provide the latest and most promising evidence on the prevalence
and determinants for folic acid supplementation in pregnant women in Japan,
including differences in prevalence between interview years and determinants
across regions. MATERIALS AND METHODS: The study participants were enrolled from
15 regional centers across Japan between January 2011 and March 2014. Information
on the use of folic acid supplementation before and during pregnancy and the
characteristics of the participants were collected using questionnaires, medical
chart reviews, and interviews by research coordinators. RESULTS: Data for 91,538
women who provided sufficient data on folic acid supplementation were analyzed.
The prevalence of adequate users was 8.0%, which, although low, tended to improve
over the 4-year recruitment period. Various kinds of sociodemographic factors,
lifestyle habits, and obstetrical and medication use history were significant and
independent determinants for folic acid use. Associations between adequate
preconception folic acid use and its major determinants tended to be similar
across regions. CONCLUSIONS: Although the prevalence of adequate folic acid use
was low, it increased from 2011 to 2014. Reproductive-aged women who have
determinants for inadequate folic acid use should be informed about the need for
preconception folic acid supplementation to help prevent neural tube defects.
PMID- 29950124
TI - A validity argument for progress testing: Examining the relation between growth
trajectories obtained by progress tests and national licensing examinations using
a latent growth curve approach.
AB - BACKGROUND: Progress testing is a longitudinal assessment that aims at tracking
students' development of knowledge. This approach is used in many medical schools
internationally. Although progress tests are longitudinal in nature, and their
focus and use of developmental aspects is a key advantage, individual students'
learning trajectories themselves play, to date, only a minor role in the use of
the information obtained through progress testing. METHODS: We investigate in how
far between-person differences in initial levels of performance and within-person
rate of growth can be regarded as distinct components of students' development
and analyze the extent to which these two components are related to performances
on national licensing examinations using a latent growth curve model. RESULTS:
Both, higher initial levels of performances and steepness of growth are
positively related to long-term outcomes as measured by performance on national
licensing examinations. We interpret these findings as evidence for progress
tests' suitability to monitor students' growth of knowledge across the course of
medical training. CONCLUSIONS: This study indicates that individual development
as obtained by formative progress tests is related to performance in high-stakes
assessments. Future studies may put more focus on the use of between-persons
differences in growth of knowledge.
PMID- 29950123
TI - Intravenous vitamin C in the treatment of allergies: an interim subgroup analysis
of a long-term observational study.
AB - : Objective Oxidative stress appears to be a key factor in the pathogenesis of
allergic diseases and a potential therapeutic target in allergy treatment.
Allergic diseases are reportedly associated with reduced plasma levels of
ascorbate, which is a key physiological antioxidant. Ascorbate prevents excessive
inflammation without reducing the defensive capacity of the immune system.
Methods An interim analysis of a multicenter, prospective, observational study
was conducted to investigate the change in disease-specific and nonspecific
symptoms (fatigue, sleep disorders, depression, and lack of mental concentration)
during adjuvant treatment with intravenous vitamin C (Pascorbin(r); Pascoe,
Giessen, Germany) in 71 patients with allergy-related respiratory or cutaneous
indications. Results Between the start and end of treatment, the mean sum score
of three disease-specific symptoms decreased significantly by 4.71 points and
that of four nonspecific symptoms decreased significantly by 4.84 points. More
than 50% of patients took no other allergy-related medication besides vitamin C.
Conclusions Our observations suggest that treatment with intravenous high-dose
vitamin C reduces allergy-related symptoms. Our observations form a basis for
planning a randomized controlled clinical trial to obtain more definitive
evidence of the clinical relevance of our findings. We also obtained evidence of
ascorbate deficiency in allergy-related diseases. TRIAL REGISTRATION: Clinical
Trials NCT02422901.
PMID- 29950125
TI - Endoscopic cystoventriculostomy of an arachnoid cyst using a neuroendovascular
stent to maintain patency.
AB - INTRODUCTION: Cystoventriculostomy is a surgical treatment for arachnoid cysts.
We present a case using a neuroendovascular stent to maintain ostomy patency.
CASE REPORT: A 61/2-year-old male with symptomatic arachnoid cyst underwent
endoscopic fenestration and Wingspan stent insertion. CONCLUSION:
Neuroendovascular stent placement may be an adjunct to maintain patency in
cystoventriculostomy.
PMID- 29950126
TI - The importance of malapposition in angiographically optimized stenting in
contemporaneous interventions.
AB - INTRODUCTION: Stenting has advanced the treatment of coronary artery disease,
with angiography being historically the gold standard to assure adequate stent
deployment. However, intravascular imaging modalities including intravascular
ultrasound and optical coherence tomography have shown high rates of inadequate
stent deployment in angiographically optimized stents. The association of
malapposition with adverse clinical outcomes remains controversial. Areas
covered: The definition, types, and risk factors for metallic stent
malapposition, the natural history, and significance of stent strut malapposition
and its correlation with short- and long-term outcomes were reviewed. Expert
commentary: Using intravascular imaging, acute stent strut malapposition is very
common, occurring in >75% in some studies. Malapposition may be a result of
inadequate stent deployment technique or the atherosclerotic process itself. The
preponderance of available data suggests that acute malapposition is not
associated with worsened outcomes. Late acquired malapposition may be associated
with a relatively increased event rate for stent thrombosis and myocardial
infarction but the increased risk is quite small (<0.01%) in absolute terms. Use
of a classification system based on cause rather than simple presence of
malapposition may clarify some of the uncertainties regarding the clinical
significance of strut malapposition.
PMID- 29950128
TI - Influence of distribution of mother's abdominal body fat on first trimester fetal
growth.
AB - OBJECTIVE: Fetal growth in the first trimester is estimated by measuring the
crown to rump length of the fetus (CRL). There are no data on the relation
between fetal growth and fat distribution in pregnant women. The objective was to
investigate the influence of fat distribution in pregnant women on fetal growth
in the first trimester of pregnancy. METHODS: This was a controlled observation
using a random sampling method. Newly registered pregnant women were included in
the sample during a 12-18-month period. The study included 400 pregnant women
from Bjelovarsko-bilogorska County, Croatia. Participants were divided into three
groups according to their pregravid BMI values, normal weight (n = 254),
overweight (n = 103), and obese (n = 43). In the 12th week of pregnancy, the CRL
was measured by transvaginal ultrasound. The subcutaneous and preperitoneal fat
was measured by transabdominal ultrasound, using the Suzuki method. The
correlation was tested by the Pearson's coefficient, and a linear regression
analysis was performed on the variables with good correlation. RESULTS: In normal
weight pregnant women, there is no correlation between the adipose tissue and
fetal length, but there is a significant correlation between overweight and obese
ones. CONCLUSION: The distribution of adipose tissue in obese and overweight
pregnant women is associated with fetal length in the first trimester of
pregnancy, with a stronger correlation between visceral fat and fetal length. The
influence of this correlation on the overall fetal growth should be investigated
by longitudinal monitoring of these variables during the entire pregnancy.
PMID- 29950127
TI - Changes in Th1/Th2-producing cytokines during acute exacerbation chronic
obstructive pulmonary disease.
AB - Objective This study aimed to explore cytokine serum levels and the ratio of type
1 T helper (Th1)/Th2 cells in patients with acute exacerbation of chronic
obstructive pulmonary disease (AECOPD). Methods A total 245 patients diagnosed
with AECOPD and 193 patients who progressed to stable COPD after the initiation
of treatment in hospital were selected, while a further 50 healthy individuals
served as controls. All patients with COPD were diagnosed using Global Initiative
for Chronic Obstructive Lung Disease criteria. Serum concentrations of
interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-10, IL-17, and
immunoglobulin (Ig)E were measured using enzyme-linked immunosorbent assays.
Results AECOPD patients had higher levels of IL-2, IFN-gamma, IL-4, IL-10, IL-17,
and IgE than those with stable COPD or controls. Intriguingly, the ratios of
Th1/Th2 and IL-17/IgE were lower in AECOPD patients compared with the other two
groups. These data suggest that AECOPD patients produce more IgE and have more
differentiated Th2 cells than other groups. Conclusion Our findings suggest that
an imbalance of circulating CD4+ T cell subsets correlates with AECOPD, and that
a shift of Th1/Th2 and IL-17/IgE ratios may be caused by increased Th2 cell
production.
PMID- 29950130
TI - Prepregnancy Body Mass Index shift across gestation: primary evidence of an
association with eating disorders.
AB - OBJECTIVE: Previous studies indicated that gestational weight gain-related
disorders share many similarities with feeding and eating disorders (EDs).
DESIGN: To examine the association of prepregnancy Body Mass Index (BMI), defined
according to 2009 Institute of Medicine (IOM), and its shift across gestation
with symptoms of feeding and EDs, defined by EDE-Q. SETTING: This prospective
cohort study took place at the Division of Perinatal Medicine of Policlinico
Abano Terme, Italy, from Jannuary 2015 to October 2015. POPULATION AND SAMPLE:
The sample included 655 healthy at term puerperae. MAIN OUTCOMES MEASURES: We
correlated gestational BMI in different women categories to EDE-Q Global score
and Restrain, Eating concern, Shape concern, and Weight concern subscales, by
Spearman's correlation test. RESULTS: Among 655 women, 59 (9.0%) were categorized
as underweight, 463 (70.7%) normal weight, 98 (15.0%) overweight, and 35 (5.3%)
as obese in prepregnancy period. At the end of gestation, underweight women
category disappeared, normal weight women lightened to one third, overweight
women tripled, and obese women doubled. At the same time, EDE-Q global scores
increased from normal weight (0.25 +/- 0.41), to overweight (0.47 +/- 0.58), and
to obese (0.72 +/- 0.70) puerperae. In addition, EDE-Q global scores were
significantly correlated with gestational BMI increase in Global score (rho =
0.326; p < .001) and in the four subscales: Restrain (rho = 0.161; p < .001),
Eating concern (rho = 0.193; p < .001), Shape concern (rho = 0.335; p < .001),
and Weight concern (rho = 0.365; p < .001), respectively. CONCLUSIONS: It was
found that the shift of woman BMI across an uncomplicated pregnancy is a warning
indicator of unhealthy eating and feeding symptoms.
PMID- 29950129
TI - Cytogenetic abnormalities in couples with a history of primary and secondary
recurrent miscarriage: a Brazilian Multicentric Study.
AB - OBJECTIVE: To evaluate the difference between chromosomal abnormalities between
the gender of couples affected by Recurrent miscarriage (RM) and if there is an
association between previous obstetric history and chromosomal abnormalities of
the parents. METHODS: Multicenter, retrospective, observational study from seven
different RM clinics between 2006 and 2016. We enrolled 707 couples (1014
participants) with a history of RM. We compared the frequency of chromosomal
abnormalities between groups of couples with primary and secondary RM and
separated between women and their partners. Furthermore, we compared the
prevalence of chromosomal abnormalities between groups based on the number of
previous spontaneous abortions. RESULTS: The overall prevalence of all
cytogenetic abnormalities was 5.59% (n = 1414, women and their partners).
Excluding cases of polymorphism and inversion of chromosome 9, which are
considered variants of normality, the prevalence in all individuals was 2.26% (n
= 32/1414). The comparative analysis of cases of chromosomal abnormalities among
couples with primary and secondary RM based on the number of previous
miscarriages (PM) revealed a similar frequency between groups. The statistical
analysis of the total cases (primary PM + secondary PM) in these three groups
were as follows: (a) couple, 2 pm versus 3 pm vs. >=4 PM, p = .514; (b) women, 2
pm versus 3 pm vs. >=4 PM, p = .347; and (3) partner, 2 pm versus 3 pm vs. >=4
PM, p = .959. Chromosomal abnormalities were significantly more prevalent among
women than among their partners (6.9 versus 4.2%; p = .027). Moreover, the
distribution of leading chromosomal abnormalities among women was different
compared with their partners. Among women, we observed these abnormalities in the
following frequency order: mosaicism (38.8%), polymorphism (32.6%), translocation
(16.3%), and inversion (12.3%). Among their partners, these abnormalities were
polymorphism (73.3%), inversion (13.3%), mosaicism (6.7%), and translocation
(6.7%). CONCLUSION: The number of PM and the history of full-term pregnancy does
not correlate with an increase or decrease in the prevalence of cytogenetic
abnormalities in couples with RM.
PMID- 29950132
TI - Role of the MAPK/cJun NH2-terminal kinase signaling pathway in starvation-induced
autophagy.
AB - : Autophagy is required for cellular homeostasis and can determine cell viability
in response to stress. It is established that MTOR is a master regulator of
starvation-induced macroautophagy/autophagy, but recent studies have also
implicated an essential role for the MAPK8/cJun NH2-terminal kinase 1 signal
transduction pathway. We found that MAPK8/JNK1 and MAPK9/JNK2 were not required
for autophagy caused by starvation or MTOR inhibition in murine fibroblasts and
epithelial cells. These data demonstrate that MAPK8/9 has no required role in
starvation-induced autophagy. We conclude that the role of MAPK8/9 in autophagy
may be context-dependent and more complex than previously considered.
ABBREVIATIONS: AKT: thymoma viral proto-oncogene;ALB: albumin; ATG4: autophagy
related 4; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, autophagy related;
BNIP3: BCL2/adenovirus E1B interacting protein 3; CQ: chloroquine diphosphate;
DMEM: Dulbecco's modified Eagle's medium; EDTA: ethylenediaminetetraacetic acid;
EBSS: Earle's balanced salt solution; FBS: fetal bovine serum; GAPDH:
glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HRAS:
Harvey rat sarcoma virus oncogene; IgG: Immunoglobulin G; MAPK3/ERK1: mitogen
activated protein kinase 3; MAPK8/JNK1: mitogen-activated protein kinase 8;
MAPK9/JNK2: mitogen-activated protein kinase 9; MAPK10/JNK3: mitogen-activated
protein kinase 10; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3
beta; MEFs: mouse embryonic fibroblasts; MTOR: mechanistic target of rapamycin
kinase; RPS6KB1/p70: ribosomal protein S6 kinase, polypeptide 1; PPARA:
peroxisome proliferator activated receptor alpha; SEM: standard error of the
mean; SQSTM1/p62: sequestosome 1; TORC1: target of rapamycin complex 1; TORC2:
target of rapamycin complex 2; TRP53: transforming related protein 53; TUBA:
tubulin alpha; UV: ultraviolet; WT: wild-type.
PMID- 29950134
TI - A comparison of dart thrower's range of motion following radioscapholunate
fusion, four-corner fusion and proximal row carpectomy.
AB - Dart thrower's motion is the functional coupled movement of the wrist from radial
extension to ulnar flexion. The aim of this study was to evaluate dart thrower's
motion following three surgeries: radioscapholunate fusion, four-corner fusion
and proximal row carpectomy. Six fresh-frozen cadaver forearms were dissected.
Sequential loading of tendons resulted in radial extension and ulnar flexion
allowing dart thrower's motion measurements at end range before and then again
after each surgery. After radioscapholunate fusion, 74% of both radial extension
and ulnar flexion were maintained. After four-corner fusion, radial extension
decreased to 53% and ulnar flexion to 84% of control motion. Proximal row
carpectomy did not statistically significantly alter radial extension, but
decreased ulnar flexion to 87%. We found that dart thrower's motion is well
maintained in three of these commonly used surgical treatments. These results may
aid surgeons in managing patients by providing comparative functional movement
following these procedures.
PMID- 29950133
TI - Base-pairing probability in the microRNA stem region affects the binding and
editing specificity of human A-to-I editing enzymes ADAR1-p110 and ADAR2.
AB - Adenosine deaminases acting on RNA (ADARs) catalyze the deamination of adenosine
(A) to inosine (I). A-to-I RNA editing targets double-stranded RNA (dsRNA), and
increases the complexity of gene regulation by modulating base pairing-dependent
processes such as splicing, translation, and microRNA (miRNA)-mediated gene
silencing. This study investigates the genome-wide binding preferences of the
nuclear constitutive isoforms ADAR1-p110 and ADAR2 on human miRNA species by RNA
immunoprecipitation of ADAR-bound small RNAs (RIP-seq). Our results suggest that
secondary structure predicted by base-pairing probability in the mainly double
stranded region of a pre-miRNA or mature miRNA duplex may determine ADAR isoform
preference for binding distinct subpopulations of miRNAs. Furthermore, we
identify 31 unique editing sites with statistical significance, 19 sites of which
are novel editing sites. Editing sites are enriched in the seed region
responsible for target recognition by miRNAs, and isoform-specific nucleotide
motifs in the immediate vicinity and opposite of editing sites are consistent
with previous studies, and further reveal that ADAR2 may edit A/C bulges more
frequently than ADAR1-p110 in the context of miRNA.
PMID- 29950135
TI - Alterations to wrist tendon forces following flexor carpi radialis or ulnaris
sacrifice: a cadaveric simulator study.
PMID- 29950136
TI - Life quality change after inflatable penile prosthesis implantation.
AB - PURPOSE: It was aimed to evaluate the changes in quality of life in patients with
erectile dysfunction (ED) after inflatable penile prosthesis implantation.
MATERIAL AND METHODS: Forty-one patients who underwent to an inflatable penile
prosthesis implantation surgery due to ED were included in the study. The age of
the patients, the indications for surgery, and the type of prosthesis implanted
were recorded. All patients were implanted two-piece inflatable (AMS AmbicorTM)
or three-piece inflatable (AMS 700TM) prostheses. A 36-item short form (SF-36)
was used to assess the life quality of patients. The scores obtained from these
forms were recorded and used to compare the preoperative and postoperative
quality of life of the patients. RESULTS: The mean age of the patients was 59.9
(38-78) years. The mean follow-up was 25.1 (12-39) months. A three-piece
inflatable penile prosthesis was implanted in 11 (26.8%) of the 41 patients and
the others were implanted with a two-piece inflatable penile prosthesis. Average
SF-36 scores were increased significantly after surgery in all groups.
CONCLUSIONS: Inflatable penile prosthesis implantation is one of the most
satisfactory treatment methods of ED and our study shows that with this treatment
the patients can be provided a significant improvement in life quality.
PMID- 29950137
TI - "It's both a strength and a drawback." How therapists' personal qualities are
experienced in their professional work.
AB - OBJECTIVE: The aim of this study was to gain knowledge about how the integration
of personal and professional experiences affects therapeutic work. METHOD:
Therapists (N = 14) who had been recommended by their leaders at their individual
workplaces were interviewed twice with semi-structured qualitative interviews,
which were then subjected to thematic and Interpretative Phenomenological
Analysis. RESULTS: All the therapists in the sample described their personal
qualities as an experienced tension between their personal strengths and
vulnerabilities in the therapeutic setting. This tension came to expression
through four subordinate themes: (a) The tension between perceiving oneself as a
helper while dealing with one's own needs for attention and care; (b) The tension
between the ability for embodied listening to the patient while tuning into
oneself; (c) The tension between staying present while handling aggression and
rejection from clients; and (d) The tension in striving for a constructive
balance between closeness and distance. CONCLUSION: The results point to ways in
which the personal selves of the therapists may affect their professional role
performance. Drawing upon previous research and literature on the topic, the
paper discusses how therapists' personal qualities are experienced as affecting
their work and suggests several implications for psychotherapy training and
practice.
PMID- 29950138
TI - Absence of sustained breast cancer incidence inflation in a national mammography
screening programme.
AB - Objective To investigate the impact of population mammography screening on breast
cancer incidence trends in New Zealand. Methods Trends in age-specific rates of
invasive breast cancer incidence (1994-2014) were assessed in relation to
screening in women aged 50-64 from 1999 and 45-69 following the programme age
extension in mid-2004. Results Breast cancer incidence increased significantly by
18% in women aged 50-64 compared with 1994-98 (p<0.0001), coinciding with the
1999 introduction of mammography screening, and remained elevated for four years,
before declining to pre-screening levels. Increases over 1994-99 incidence
occurred in the 45-49 (21%) and 65-69 (19%) age groups following the 2004 age
extension (p<0.0001). Following establishment of screening (2006-10), elevated
incidence in the screening target age groups was compensated for by lower
incidence in the post-screening ?70 age groups than in 1994-98. Incidence in
women aged ?45 was not significantly higher (+5%) after 2006 than in 1994-98. The
cumulated risk of breast cancer in women aged 45-84 for 1994-98 was 10.7%
compared with 10.8% in 2006-10. Conclusions Increases in breast cancer incidence
following introduction of mammography screening in women aged 50-64 did not
persist. Incidence inflation also occurred after introduction of screening for
age groups 45-49 and 65-69. The cumulated incidence for women aged 45-84 over
2006-10 after screening was well established, compared with 1994-98 prior to
screening, shows no increase in diagnosis. Over-diagnosis is not inevitable in
population mammography screening programmes.
PMID- 29950139
TI - Usability Testing of an Interactive Virtual Reality Distraction Intervention to
Reduce Procedural Pain in Children and Adolescents With Cancer [Formula: see
text].
AB - PURPOSE: Needle procedures are among the most distressing aspects of pediatric
cancer-related treatment. Virtual reality (VR) distraction offers promise for
needle-related pain and distress given its highly immersive and interactive
virtual environment. This study assessed the usability (ease of use and
understanding, acceptability) of a custom VR intervention for children with
cancer undergoing implantable venous access device (IVAD) needle insertion.
METHOD: Three iterative cycles of mixed-method usability testing with
semistructured interviews were undertaken to refine the VR. RESULTS: Participants
included 17 children and adolescents (8-18 years old) with cancer who used the VR
intervention prior to or during IVAD access. Most participants reported the VR as
easy to use (82%) and understand (94%), and would like to use it during
subsequent needle procedures (94%). Based on usability testing, refinements were
made to VR hardware, software, and clinical implementation. Refinements focused
on increasing responsiveness, interaction, and immersion of the VR program,
reducing head movement for VR interaction, and enabling participant alerts to
steps of the procedure by clinical staff. No adverse events of nausea or
dizziness were reported. CONCLUSIONS: The VR intervention was deemed acceptable
and safe. Next steps include assessing feasibility and effectiveness of the VR
intervention for pain and distress.
PMID- 29950140
TI - Consequences on aging process and human wellness of generation of nitrogen and
oxygen species during strenuous exercise.
AB - Impairment of antioxidant defense system and increase in metabolic rate and
production of reactive oxygen species have been demonstrated in strenuous
exercise. Both at rest and during contractile activity, skeletal muscle generates
a very complex set of reactive nitrogen and oxygen species; the main generated
are superoxide and nitric oxide. The nature of the contractile activity
influences the pattern and the magnitude of this reactive oxygen and nitrogen
species (ROS) generation. The intracellular pro-oxidant/antioxidant homeostasis
undergoes alteration owing to strenuous exercise and the major identified sources
of intracellular free radical generation during physical activity are the
mitochondrial electron transport chain, polymorphoneutrophil, and xanthine
oxidase. Reactive oxygen species increased tissue susceptibility to oxidative
damage and pose a serious threat to the cellular antioxidant defense system. The
possible dangerous consequences of the aging process and human wellness are
emphasized in this review.
PMID- 29950141
TI - TNF-alpha induces autophagy through ERK1/2 pathway to regulate apoptosis in
neonatal necrotizing enterocolitis model cells IEC-6.
AB - Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature
neonates. Tumor necrosis factor-alpha (TNF-alpha) and autophagy are associated
with the pathogenesis of NEC. This study aimed to explore whether TNF-alpha might
regulate apoptosis in neonatal NEC model cells IEC-6 via regulation of autophagy.
NEC rat model was induced by hand feeding and exposure to asphyxia/cold-stress
for histologic examination. The NEC in vitro model (IEC-6/NEC cells) was
established by stimulating the intestinal epithelial cell line IEC-6 with
lipopolysaccharide (LPS, 100 MUg/mL) for 3 h to investigate the effects of TNF
alpha on IEC-6 proliferation and apoptosis. In this study, NEC rats showed
decreased proliferating cell nuclear antigen (PCNA) expression, increased TUNEL
positive cells, higher expression of TNF-alpha, p-ERK1/2, and autophagy-related
proteins in rat small intestine compared with their controls. Additionally, the
LPS-stimulated IEC-6/NEC cells showed a significantly decreased proliferation and
increased apoptosis compared with the control cells. Furthermore, the LPS
stimulated IEC-6/NEC cells exhibited enhanced autophagy level, as evidenced by a
dose-dependent increase in Beclin-1 protein expression, LC3II/LC3I ratio and
accumulation of MDC-positive autophagic vacuoles. Moreover, inhibition of
autophagy by wortmannin or LY294002 significantly abolished the LPS-mediated
decreased proliferation and increased apoptosis of IEC-6/NEC cells. Results also
showed that inhibition of ERK1/2 pathway using U0126 significantly inhibited TNF
alpha-induced autophagy. Furthermore, the TNF-alpha-mediated inhibition of IEC-6
proliferation and promotion of IEC-6 apoptosis was abolished by U0126. Our
findings demonstrated that TNF-alpha might induce autophagy through ERK1/2
pathway to regulate apoptosis in neonatal NEC cells IEC-6. Our study enhances our
understanding of neonatal NEC pathogenesis.
PMID- 29950143
TI - Can bone-regulating hormones and nutrients help characterize the metabolically
healthy obese phenotype.
AB - BACKGROUND:: Bone-regulating hormones and nutrients play an important role in
influencing metabolic health. AIM:: The aim of this study was to determine
whether bone-regulating hormones and nutrients, such as parathyroid hormone
(PTH), 25-hydroxyvitamin D (25OHD), and magnesium (Mg) could be used to
characterize the metabolically healthy obese (MHO) phenotype. METHODS:: This
study included 27 overweight or obese participants (14 men/13 women) classified
as MHO ( n = 14) or metabolically unhealthy obese (MUO) ( n = 13) based on the
presence or absence of metabolic abnormalities, determined by percentage body
fat, percentage trunk fat, and waist circumference. Biochemical (serum
concentrations of hormones and cytokines such as PTH, 25OHD, ionized Mg (iMg),
cytokines, lipids, glycemic indices), physiological (percentage body fat,
percentage trunk fat, blood pressure (BP)), and dietary intake (Mg intake,
calcium intake) measurements were obtained. RESULTS:: Serum PTH concentrations
were significantly lower ( p = 0.005) in the MHO group (39.68 +/- 11.06 pg/mL)
compared with the MUO group (63.78 +/- 25.82 pg/mL). Serum iMg concentrations
were higher ( p = 0.052) in the MHO group (0.565 +/- 0.41 mmol/L) than in the MUO
group (0.528 +/- 0.050 mmol/L). Serum concentrations of osteocalcin were also
higher (10.37 +/- 3.70 ng/mL) in the MHO compared with the MUO (6.51 +/- 4.14
ng/mL) group ( p = 0.017). The MHO group had significantly lower serum insulin
concentrations ( p = 0.006) and diastolic BP ( p = 0.035). Concentrations of
serum 25OHD, total triglycerides, C-reactive protein and systolic BP did not
differ between groups. CONCLUSIONS:: These findings suggest that bone-regulating
hormones and nutrients, especially serum PTH, osteocalcin concentrations, and
dietary Mg intakes, can help to characterize the MHO phenotype.
PMID- 29950142
TI - Transcription factor NFE2L2/NRF2 modulates chaperone-mediated autophagy through
the regulation of LAMP2A.
AB - : Chaperone-mediated autophagy (CMA) is a selective degradative process for
cytosolic proteins that contributes to the maintenance of proteostasis. The
signaling mechanisms that control CMA are not fully understood but might involve
response to stress conditions including oxidative stress. Considering the role of
CMA in redoxtasis and proteostasis, we sought to determine if the transcription
factor NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2) has an impact on
CMA modulation. In this work, we identified and validated 2 NFE2L2 binding
sequences in the LAMP2 gene and demonstrated in several human and mouse cell
types that NFE2L2 deficiency and overexpression was linked to reduced and
increased LAMP2A levels, respectively. Accordingly, lysosomal LAMP2A levels were
drastically reduced in nfe2l2-knockout hepatocytes, which also displayed a marked
decrease in CMA activity. Oxidant challenge with paraquat or hydrogen peroxide,
or pharmacological activation of NFE2L2 with sulforaphane or dimethyl fumarate
also increased LAMP2A levels and CMA activity. Overall, our study identifies for
the first time basal and inducible regulation of LAMP2A, and consequently CMA
activity, by NFE2L2. ABBREVIATIONS: ACTB: actin, beta, ARE: antioxidant response
element; ATG5: autophagy related 5; BACH1: BTB domain and CNC homolog 1; ChIP:
chromatin immunoprecipitation; CMA: chaperone-mediated autophagy; DHE:
dihydroethidium; DMF: dimethyl fumarate; ENCODE: Encyclopedia of DNA elements at
the University of California, Santa Cruz; GAPDH: glyceraldehyde-3-phosphate
dehydrogenase; GBA: glucosylceramidase beta; GFP: green fluorescent protein;
HMOX1: heme oxygenase 1; H2O2: hydrogen peroxide; HSPA8/HSC70: heat shock protein
family A (Hsp70) member 8; KEAP1: kelch like ECH associated protein 1; LAMP2A:
lysosomal associated membrane protein 2A; LAMP2B: lysosomal associated membrane
protein 2B; LAMP2C: lysosomal associated membrane protein 2C; LAMP1: lysosomal
associated membrane protein 1; MAFF: MAF bZIP transcription factor F; MAFK: MAF
bZIP transcription factor K; NFE2L2/NRF2: nuclear factor, erythroid derived 2,
like 2; NQO1: NAD(P)H quinone dehydrogenase 1; PQ: paraquat; PI: protease
inhibitors; qRT-PCR: quantitative real-time polymerase chain reaction; RNASE:
ribonuclease A family member; SFN: sulforaphane; SQSTM1/p62: sequestosome 1; TBP:
TATA-box binding protein.
PMID- 29950145
TI - Pitch direction ability predicts melodic perception in autism.
AB - Individuals with autism spectrum disorders (ASDs) often present atypical auditory
perception. Previous work has reported both enhanced low-level pitch
discrimination and superior abilities to detect local pitch structure on higher
level melodic tasks in ASD. However, it is unclear how low and high levels of
auditory perception are related in ASD or typical development (TD), or how this
relationship might change across development and stimulus presentation rates. To
these aims, in the present study, children with ASD and TD were tested on a low
level pitch direction discrimination task and a high-level melodic global-local
task. Groups performed similarly on both of these auditory tasks. Moreover,
individual differences in low-level pitch direction ability predicted performance
on the higher-level global-local task, with a stronger relationship in ASD. Age
did not affect the relationship between low-level and high-level pitch
performance in either ASD or TD. However, there was a more positive effect of age
on the high-level global-local task performance in TD than ASD. Finally, there
was no effect of stimulus rate on the relationship between low-level and high
level pitch performance in either group. These findings provide a better
understanding of how perception is associated across levels of processing in ASD
versus TD. This work helps to better understand individual differences in
auditory perception and to refine ASD phenotypes.
PMID- 29950144
TI - LncRNA H19-elevated LIN28B promotes lung cancer progression through sequestering
miR-196b.
AB - LncRNA H19 is involved in the development of multiple cancers. Here, we firstly
provide new evidence that H19 can induce LIN28B, a conserved RNA binding protein,
to accelerate lung cancer growth through sponging miR-196b. Abundance in LIN28B
was observed in clinical lung cancer samples. A positive link was observed
between H19 and LIN28B in clinical lung cancer samples. In lung cancer cells, H19
was capable of increasing LIN28B expression. Mechanistically, miR-196b directly
targeted LIN28B to inhibit LIN28B expression. H19 was capable of promoting LIN28B
expression through sequestering miR-196b. Functionally, H19-increased LIN28B
conferred the cell proliferation of lung cancer. Our finding indicates that H19
depresses miR-196b to elevate LIN28B, resulting in accelerating cell
proliferation in lung cancer.
PMID- 29950146
TI - Octamer-binding transcription factor 4 correlates with complex karyotype, FLT3
ITD mutation and poorer risk stratification, and predicts unfavourable prognosis
in patients with acute myeloid leukaemia.
AB - Objective To investigate the correlation of octamer-binding transcription factor
4 (OCT4) expression with clinicopathological features and its predictive value
for treatment response as well as survival profiles in de novo acute myeloid
leukaemia (AML) patients. Method One hundred fifty-two de novo AML patients and
52 non-hematologic malignancy patients were recruited in this prospective cohort
study. OCT4 expression was determined in bone marrow sample collected before
treatment. Complete response (CR), event free survival (EFS) and overall survival
(OS) were evaluated. Results Compared with the controls, OCT4 mRNA expression was
higher in AML patients (P < .001), and higher OCT4 expression was correlated with
presence of complex karyotype (CK) (P = .037), FLT3-ITD mutation (P = .012) and
poorer risk stratification (P < .001) in AML patients. As to predictive value,
OCT4 mRNA expression was decreased in patients achieved CR compared to non-CR
patients (P = .022). Kaplan-Meier (K-M) curves showed that shorter EFS (9.0 (95%
CI (7.7-10.3)) months vs. 25.0 (95% CI (17.5-32.5)) months, P < .001) and shorter
OS (20.0 (95% CI (17.8-22.2) months vs. 33.0 months, P < .001) were observed in
OCT4 mRNA high expression patients compared to OCT4 mRNA low expression patients.
Multivariate Cox's proportional hazards regression analyses revealed that OCT4
mRNA high expression was an independent predictive factor for shorter EFS and OS
in AML patients. Conclusion OCT4 correlates with presence of CK, FLT3-ITD
mutation and poorer risk stratification, and it could be served as a convincing
biomarker for predicting unfavourable prognosis in AML patients.
PMID- 29950147
TI - End-of-life care in a nursing home: Assistant nurses' perspectives.
AB - BACKGROUND: Worldwide, older persons lack access to palliative care. In Sweden,
many older persons die in nursing homes where care is provided foremost by
assistant nurses. Due to a lack of beds, admission is seldom granted until the
older persons have complex care needs and are already in a palliative phase when
they move in. OBJECTIVE: To describe assistant nurses' perspectives of providing
care to older persons at the end of life in a nursing home. RESEARCH DESIGN: Data
were collected in semi-structured individual interviews and analyzed with
inductive qualitative content analysis. Participants and research context: Seven
assistant nurses from a nursing home in Sweden were randomly selected. Ethical
consideration: The research was approved by the local ethics committee. RESULTS:
Three main categories emerged; "Death a natural part of life"; "The older
person's well-being"; and "Care in the moment of death"; and seven sub
categories. The assistant nurses described themselves as knowing the older
persons well enough to provide good end-of-life care. This was achieved by making
small-talk while providing daily care. Relying on experience-based knowledge,
they strove to provide end-of-life care built upon respect and engagement with
the ambition to strengthen older persons' dignity, for example, by lowering the
tempo of care at the end of life, in spite of organizational restrictions.
DISCUSSION: The assistant nurses offered attentive end-of-life care, focusing
upon bodily care. The existential needs of the older persons were not
foregrounded. CONCLUSION: To develop their work, and to promote an ethical
foundation for such care, assistant nurses might need support and education to be
able to offer a care more in line with the aims of palliative care. Furthermore,
the organization of care needs to promote, not impede, the realization of this
development.
PMID- 29950148
TI - Can clinical pharmacists bridge a gap between medical oncologists and patients in
resource-limited oncology settings? An experience in Nepal.
AB - The clinical pharmacist's part is emerging as a key extension to the human
services care team bringing about enhanced patient care in the world. The main
objective of this article is to highlight the role of clinical pharmacist in an
oncology setting of Nepal. An enrollment of clinical pharmacist in an oncology
hospital or in oncology settings can work as a bridge between medical oncologist
and patients.
PMID- 29950149
TI - Field evaluation of onsite near real-time monitors for surface contamination by 5
fluorouracil.
AB - Objectives In order to produce near real-time onsite results to detect surface
contamination by antineoplastic drugs, the National Institute for Occupational
Safety and Health developed monitors for 5-fluorouracil, which use surface wiping
and lateral flow immunoassay for measurement. The monitors were tested in the
laboratory to assess the sensitivity of detection on laboratory-produced
contaminated surfaces. A field evaluation to assess the capability of the
monitors to make measurements in healthcare workplaces was carried out in
collaboration with a medical device company and the results are presented in this
report. Methods The 5-fluorouracil monitor was evaluated in areas where oncology
drugs were prepared and administered to patients at five different hospitals. The
levels of contamination measured with the monitors were compared to levels
measured with liquid chromatography-tandem mass spectrometry. Results The 5
fluorouracil values measured with the liquid chromatography-tandem mass
spectrometry ranged from 0 to over 200,000 ng/100 cm2. Measurements by the 5
fluorouracil monitors in the range 10-100 ng/100 cm2 correlated with the liquid
chromatography-tandem mass spectrometry. Receiver operating characteristic curves
developed for the data indicated that a positive limit of 22 ng/100 cm2 would
give an acceptable level of false-positives while retaining most true-positive
samples. If the liquid chromatography-tandem mass spectrometry measured greater
than 100 ng/100 cm2, then the monitors also measured levels greater than 100
ng/100 cm2 for the majority of samples. Conclusion The data indicate that there
are many areas in hospitals that are contaminated with 5-fluorouracil and the
monitors will be useful in identifying this contamination.
PMID- 29950150
TI - Implementation of a text message intervention to promote behavioural change and
weight loss among overweight and obese Brazilian primary care patients.
AB - Introduction Mobile-technology-based interventions are promising strategies for
promoting behavioural change in obese patients. The aims of this study were to
evaluate the feasibility of implementing a text message intervention, and to
assess the effects of the intervention on body mass index (BMI) and self-reported
behavioural change. Methods TELEFIT was a three-phase feasibility study
comprising the following stages: (a) the development of text messages; (b)
testing; and (c) a quasi-experimental pilot study in which patients who were
engaged in obesity/overweight educational groups in public primary care centres
in Belo Horizonte, Brazil, were recruited. A bank of text messages was drafted
and reviewed by an expert panel, text message delivery software was developed and
tested, and a pilot study assessed patients before and after receiving the
intervention using validated questionnaires and body measures. The data were
analysed using the Wilcoxon test. Results A total of 46 patients completed the
follow-up; 93.5% were women and the median age was 42 years (interquartile range
(IQR) 34-52 years). At four months, participants had a significant reduction in
BMI (median 31.3 (IQR 28.2-34.6) vs. 29.9 (IQR 27.2-34.6) kg/m2, p < 0.001),
systolic (median 125 (IQR 120-132) vs. 120 (IQR 110-130) mmHg, p = 0.013) and
diastolic blood pressure (median 80 (IQR 70-100) vs. 80 (IQR 70-80) mmHg, p =
0.006), when compared to baseline. All patients reported to be satisfied and
willing to continue receiving the intervention, and 93.3% felt that the
intervention helped them change their behaviours. Discussion This study has shown
that a text message intervention to promote behavioural change and weight loss
was feasible and effective in a short-term period. Participants were satisfied
and willing to continue receiving the SMS messages.
PMID- 29950152
TI - IL-33 Promotes the Development of Colorectal Cancer Through Inducing Tumor
Infiltrating ST2L+ Regulatory T Cells in Mice.
AB - Colorectal cancer, one of the most commonly diagnosed and lethal cancers
worldwide, is accompanied by the disorders of immune system. However, the
underlying mechanism is still not fully understood. In this study, our goal was
to determine whether interleukin 33 promotes tumorigenesis and progression of
colorectal cancer through increased recruitment of tumor-infiltrating ST2+
regulatory T cells in CT26 tumor-bearing mice. We found that the mRNA or protein
levels of interleukin 33, soluble ST2, and membrane ST2 were elevated in the
serum of tumor-bearing mice when compared to WT mice. The mRNA levels of
interleukin 33, soluble ST2, and membrane ST2 were also elevated in the tissue of
tumor-bearing mice when compared to surrounding nontumor muscular tissues. In
addition, the frequency of ST2L+ regulatory T cells was significantly increased
in both tumor tissue and spleen of tumor-bearing mice. Higher protein levels of
interleukin-4, -10, and -13 were also observed in the serum or the tumor
homogenates of tumor-bearing mice. We found exogenously administered recombinant
mouse interleukin 33 promoted tumor size and induced tumor-infiltrating ST2L+
regulatory T cells in tumor-bearing mice while neutralizing interleukin-33 or
ST2L inhibited tumor size and decreased ST2L+ regulatory T cells. Furthermore,
ST2L+ regulatory T cells from tumor tissue were also able to suppress CD4+CD25-T
cell proliferation and interferon gamma production. Altogether, our findings
demonstrate the critical roles of interleukin 33 in promoting colorectal cancer
development through inducing tumor-infiltrating ST2L+ regulatory T cells, and
inhibition of interleukin-33/ST2L signaling maybe a potential target for the
prevention of colorectal cancer.
PMID- 29950151
TI - High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients
With ESCC.
AB - Esophageal squamous cell carcinoma is the sixth most lethal cancer worldwide and
the fourth most lethal cancer in China. Tissue-specific transplantation antigen
P35B codifies the enzyme GDP-d-mannose-4,6-dehydratase, which participates in the
biosynthesis of GDP-l-fucose. GDP-l-fucose is an important substrate involved in
the biosynthesis of many glycoproteins. Cancer cells are often accompanied by the
changes in glycoprotein structure, which affects the adhesion, invasion, and
metastasis of cells. It is not clear whether tissue-specific transplantation
antigen P35B has any effect on the development of esophageal squamous cell
carcinoma. We used an immunohistochemical method to assess the expression of
tissue-specific transplantation antigen P35B in 104 esophageal squamous cell
carcinoma samples. The results showed tissue-specific transplantation antigen
P35B expression was associated with some clinical features in patients, such as
age ( P = .017), clinical stage ( P = .010), and lymph node metastasis ( P =
.043). Kaplan-Meier analysis and log-rank test showed that patients with
esophageal squamous cell carcinoma having high tissue-specific transplantation
antigen P35B expression had a worse prognosis compared to the patients with low
expression ( P = .048). Multivariate Cox proportional hazards regression model
showed that high expression of tissue-specific transplantation antigen P35B could
predict poor prognosis for patients with esophageal squamous cell carcinoma
independently. In conclusion, abnormal fucosylation might participate in the
progress of esophageal squamous cell carcinoma and tissue-specific
transplantation antigen P35B may serve as a novel biomarker for prognosis of
patients with esophageal squamous cell carcinoma.
PMID- 29950153
TI - The ERK/CREB pathway is involved in the c-Ski expression induced by low TGF-beta1
concentrations during primary fibroblast proliferation.
AB - Increasing evidence has suggested that bidirectional regulation of cell
proliferation is one important effect of TGF-beta1 in wound healing. Increased c
Ski expression plays a role in promoting fibroblast proliferation at low TGF
beta1 concentrations, but the mechanism by which low TGF-beta1 concentrations
regulate c-Ski levels remains unclear. In this study, the proliferation of rat
primary fibroblasts was assessed with an ELISA BrdU kit. The mRNA and protein
expression and phosphorylation levels of corresponding factors were measured by
RT-qPCR, immunohistochemistry or Western blotting. We first found that low TGF
beta1 concentrations not only promoted c-ski mRNA and protein expression in rat
primary fibroblasts but also increased the phosphorylation levels of
Extracellular Signal-Regulated Kinases (ERK) and cAMP response element binding
(CREB) protein. An ERK kinase (mitogen-activated protein kinase kinase, MEK)
inhibitor significantly inhibited ERK1/2 phosphorylation levels, markedly
reducing c-Ski expression and CREB phosphorylation levels and abrogating the
growth-promoting effect of low TGF-beta1 concentrations. At the same time,
Smad2/3 phosphorylation levels were not significantly changed. Taken together,
these results suggest that the increased cell proliferation induced by low TGF
beta1 concentrations mediates c-Ski expression potentially through the ERK/CREB
pathway rather than through the classic TGF-beta1/Smad pathway.
PMID- 29950154
TI - Right-to-Work-for-Less: How Janus v. AFSCME Threatens Public Health.
AB - In February 2018, the Supreme Court heard oral arguments in Janus v. AFSCME, a
case poised to make right-to-work (or, as some call it, right-to-work-for-less)
the law in the public sector. At issue is the constitutionality of requiring non
union members, who benefit from collective bargaining, to pay fees that support
contract negotiations on the terms and conditions of their employment. We argue
that a win for Janus would threaten public health by eroding organized labor's
power to improve working conditions. Furthermore, we critique the dubious legal
theory underpinning Janus's case and describe the moneyed political interests
backing his legal representation. Finally, we chart a path forward for labor
organizing in a post- Janus world, drawing inspiration from the winter 2018
educators' strike in West Virginia. Regardless of how Janus itself is decided,
the issues raised in this article remain crucial because the ongoing weakening of
unions by legislative and judicial means undermines workers' health and
exacerbates inequities.
PMID- 29950155
TI - In silico elucidation of novel anticancer lead molecules targeting human prostate
specific gene-1 protein.
PMID- 29950156
TI - An objective scoring method to evaluate image quality of middle cerebral artery
Doppler.
AB - OBJECTIVE: To validate an objective scoring system for middle cerebral artery
(MCA) pulsed wave Doppler images. METHOD: From an image database of routine 36
week scans, a random sample of MCA Doppler images was selected. Two reviewers
rated the images subjectively as acceptable or unacceptable. Subsequently they
used an objective 6-point image scoring system and awarded one point for each of:
1) anatomical site; 2) magnification; 3) angle of insonation; 4) image clarity;
5) sweep speed adjustment; and 6) velocity scale and baseline adjustment. Image
scores 4-6 were defined as good quality whereas 0-3 as poor. The subjective and
objective agreement between the two reviewers was compared using the adjusted
Kappa statistic. RESULTS: A total of 124 images were assessed. Using objective
scoring the agreement rate between reviewers increased to 91.9% (k = 0.839)
compared to subjective agreement 75.8% (k = 0.516). The agreement for each
criterion was: anatomical site 91.1% (k = 0.823); magnification 95.2% (k =
0.903); clarity 83.9% (k = 0.677); angle 96.0% (k = 0.919); sweep speed 98.4% (k
= 0.968); velocity scale and baseline 94.4% (k = 0.887). CONCLUSION: Objective
assessment of MCA Doppler images using a 6-point scoring system has greater
interobserver agreement than subjective assessment and could be used for MCA
Doppler quality assurance.
PMID- 29950157
TI - Demineralized bone matrix-based microcarrier scaffold favors vascularized large
bone regeneration in vivo in a rat model.
AB - Insufficient neo-vascularization of in vivo implanted cell-seeded scaffold
remains a major bottleneck for clinical translation of engineered bone formation.
Demineralized bone matrix is an ideal bone scaffold for bone engineering due to
its structural and biochemical components similar to those of native bone. We
hypothesized that the microcarrier form of demineralized bone matrix favors
ingrowth of vessels and bone regeneration upon in vivo implantation. In this
study, a rat model of femoral vessel pedicle-based bone engineering was employed
by filling the demineralized bone matrix scaffolds inside a silicone chamber that
surrounded the vessel pedicles, and to compare the efficiency of vascularized
bone regeneration between microcarrier demineralized bone matrix and block
demineralized bone matrix. The results showed that bone marrow stem cells better
adhered to microcarrier demineralized bone matrix and produced more extracellular
matrices during in vitro culture. After in vivo implantation, microcarrier
demineralized bone matrix seeded with bone marrow stem cells formed relatively
more bone tissue than block demineralized bone matrix counterpart at three months
upon histological examination. Furthermore, micro-computed tomography three
dimensional reconstruction showed that microcarrier demineralized bone matrix
group regenerate significantly better and more bone tissues than block
demineralized bone matrix both qualitatively and quantitatively (p < 0.05).
Moreover, micro-computed tomography reconstructed angiographic images also
demonstrated significantly enhanced tissue vascularization in microcarrier
demineralized bone matrix group than in block demineralized bone matrix group
both qualitatively and quantitatively (p < 0.05). Anti-CD31 immunohistochemical
staining of (micro-) vessels and semi-quantitative analysis also evidenced
enhanced vascularization of regenerated bone in microcarrier demineralized bone
matrix group than in block demineralized bone matrix group (p < 0.05). In
conclusion, the microcarrier form of demineralized bone matrix is an ideal bone
regenerative scaffold due to its advantages of osteoinductivity and vascular
induction, two essentials for in vivo bone regeneration.
PMID- 29950158
TI - Have a look around: The effect of physical environments on risk behaviour in work
related vs. non-work related decision-making tasks.
AB - Due to ubiquitous computing, knowledge workers do not only work in typical work
associated environments (e.g., the office) but also wherever it best suits their
schedule or preferences (e.g., the park). In two experiments using laboratory and
field methods, we compared decision making in work and non-work environments. We
hypothesised that participants make riskier work-related decisions when in work
associated environments and riskier non-work-related decisions in non-work
associated environments. Therefore, if environment (work vs. non-work) and
decision-making task (work-related vs. non-work-related) are incongruent, then
risk-taking should be lower, as the decision maker might feel the situation is
unusual or inappropriate. Although results do not reveal that work-associated
environments generally encourage riskier work-related decisions (and likewise for
non-work), we found environmental effects on decision making when including mood
as a moderator.
PMID- 29950159
TI - Distinct regional brain atrophy pattern in multiple sclerosis and
neuropsychiatric systemic lupus erythematosus patients.
AB - Differentiation of systemic lupus erythematosus (SLE) from multiple sclerosis
(MS) can be challenging, especially when neuropsychiatric (NP) symptoms are
accompanied by white matter lesions in the brain. Given the lack of
discriminative power of currently applied tools for their differentiation, there
is an unmet need for other measures that can aid in distinguishing between the
two autoimmune disorders. In this study we aimed at exploring whether brain
atrophy measures could serve as markers differentiating MS and SLE. Thirty-seven
relapsing-remitting MS and 38 SLE patients with nervous system manifestations,
matched according to age and disease duration, underwent 1.5 Tesla magnetic
resonance imaging (MRI), including volumetric sequences, and clinical assessment.
Voxelwise analysis was performed using ANTS-SyN elastic registration protocol,
FSL Randomise and Gamma methods. Cortical and subcortical segmentation was
performed with Freesurfer 5.3 pipeline using T1-weighted MPRAGE sequence data.
Using MRI volumetric markers of general and subcortical gray matter atrophy and
clinical variables, we built a stepwise multivariable logistic diagnostic model
to identify MRI parameters that best differentiate MS and SLE patients. We found
that the best volumetric predictors to distinguish them were: fourth ventricle
volume (sensitivity 0.86, specificity 0.57, area under the curve, AUC 0.77),
posterior corpus callosum (sensitivity 0.81, specificity 0.57, AUC 0.68), and
third ventricle to thalamus ratio (sensitivity 0.42, specificity 0.84, AUC 0.65).
The same classifiers were identified in a subgroup analysis that included
patients with a short disease duration. In MS brain atrophy and lesion load
correlated with clinical disability, while in SLE age was the main determinant of
brain volume. This study proposes new imaging parameters for differential
diagnosis of MS and SLE with central nervous system involvement. We show there is
a different pattern of atrophy in MS and SLE, and the key structural volumes that
are differentially affected include fourth ventricle and posterior section of
corpus callosum, followed by third ventricle to thalamus ratio. Different
correlation patterns between volumetric and clinical data may suggest that while
in MS atrophy is driven mainly by disease activity, in SLE it is mostly
associated with age. However, these results need further replication in a larger
cohort.
PMID- 29950160
TI - Synergistic effect of cumulative corticosteroid dose and immunosuppressants on
avascular necrosis in patients with systemic lupus erythematosus.
AB - Objectives Avascular necrosis (AVN) is one of the most common causes of organ
damage in patients with systemic lupus erythematosus (SLE) and often causes
serious physical disability. The aims of this study were to investigate clinical
risk factors associated with symptomatic AVN and to analyze their synergistic
effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled
and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was
measured annually according to the Systemic Lupus International Collaborating
Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by
imaging study if patients had symptoms. To determine risk factors for AVN,
clinical, laboratory and therapeutic variables were analyzed by logistic
regression. Relative excess risk due to interaction (RERI), attributable
proportion (AP), and synergy index (S) were calculated to measure interactions
between significant variables. Results Among 1219 SLE patients, symptomatic AVN
was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients
with AVN showed an earlier onset age, demonstrated AVN more commonly in
conjunction with certain other clinical manifestations such as renal and
neuropsychiatric disorders, and received significantly higher total cumulative
corticosteroid dose and immunosuppressive agents than did patients without AVN.
However, in multivariable analysis, only two variables including use of a
cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p =
0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate
mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN.
Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had
a 15.44-fold increased risk for AVN, compared with patients without these risk
factors ( p < 0.001). RERI, AP and S, which define the strength of interactions
between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73),
0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the
presence of synergistic interactions in the development of symptomatic AVN in our
Korean lupus cohort. Conclusions An individual risk assessment for AVN
development should be made prior to and during treatment for SLE, especially in
patients with high-dose corticosteroid and immunosuppressant use regardless of
clinical manifestations and disease activity.
PMID- 29950161
TI - Visual subcircuit-specific dysfunction and input-specific mispatterning in the
superior colliculus of fragile X mice.
AB - BACKGROUND: Sensory processing deficits are frequently co-morbid with
neurodevelopmental disorders. For example, patients with fragile X syndrome
(FXS), caused by a silencing of the FMR1 gene, exhibit impairments in visual
function specific to the dorsal system, which processes motion information.
However, the developmental and circuit mechanisms underlying this deficit remain
unclear. Recently, the superior colliculus (SC), a midbrain structure regulating
head and eye movements, has emerged as a model for dissecting visual circuit
development and function. Previous studies have demonstrated a critical role for
activity-dependent processes in the development of visual circuitry in the SC.
Based on the known role of the FMR1 gene product in activity-dependent synaptic
plasticity, we explored the function and organization of visual circuits in the
SC of a mouse model of FXS (Fmr1-/y). METHODS: We utilized in vivo extracellular
electrophysiology in combination with computer-controlled visual stimuli to
determine the receptive field properties of visual neurons in the SC of control
and Fmr1-/y mice. In addition, we utilized anatomical tracing methods to assess
the organization of visual inputs to the SC and along the retinogeniculocortical
pathway. RESULTS: Receptive fields of visual neurons in the SC of Fmr1-/y mice
were significantly larger than those found in control animals, though their shape
and structure were unaffected. Further, selectivity for direction of movement was
decreased, while selectivity to axis of movement was unchanged. Interestingly,
axis-selective (AS) neurons exhibited a specific hyperexcitability in comparison
to AS neurons in control SC and to direction-selective (DS) neurons in both
control and Fmr1-/y SC. Anatomical tracings revealed that retinocollicular,
retinogeniculate, and geniculocortical projections were normally organized in the
absence of Fmr1. However, projections from primary visual cortex (V1) to the SC
were poorly refined. CONCLUSIONS: Fmr1 is required for the proper development of
visual circuit organization and function in the SC. We find that visual
dysfunction is heterogeneously manifested in a subcircuit-specific manner in Fmr1
/y mice, consistent with previous studies in human FXS patients. Further, we show
a specific alteration of inputs to the SC from V1, but not the retina. Together,
these data suggest that Fmr1 may function in distinct ways during the development
of different visual subcircuits.
PMID- 29950162
TI - Bacteriological profile and antibiotic susceptibility of neonatal sepsis in
neonatal intensive care unit of a tertiary hospital in Nepal.
AB - BACKGROUND: Neonatal sepsis, one of the leading causes of mortality in neonatal
intensive care units (NICU) of developing countries like Nepal, is often not
extensively studied. In order to decrease the morbidity and mortality associated
with neonatal sepsis, neonatologists should have a keen knowledge of the existing
bacteriological flora and their antibiotic susceptibility pattern. In this study,
we aim to determine the bacteriological profile and antibiotic susceptibility
pattern of culture positive neonatal sepsis in the NICU of a tertiary teaching
hospital in Nepal. METHODS: This was a retrospective cross-sectional study of all
blood culture positive sepsis cases among neonates admitted to the neonatal
intensive care unit of Patan Hospital, Nepal between April 15, 2014 and April 15,
2017. All neonates with a clinical suspicion of sepsis with a positive blood
culture were identified. Patient demographics, clinical details, maternal risk
factors, and laboratory data including bacteriological profiles and antimicrobial
susceptibilities were recorded and analyzed. RESULTS: Of the 336 neonates
admitted in the NICU, 69 (20.5%) had culture-positive sepsis. The majority were
early-onset sepsis (n = 54, 78.3%) and were among the preterm babies (n = 47,
68.1%). Most bacterial isolates were gram-negative, predominantly the Klebsiella
species (n = 23, 33.3%). Klebsiella showed high resistance to commonly used
antibiotics such as; Cefotaxime (90.5%), Gentamicin (75%), Ciprofloxacin (76.2%),
Ofloxacin (72.2%) and Chloramphenicol (65%). However, they showed good
susceptibility to Carbapenems (100%), Colistin (88.8%) and Tigecycline (81.8%).
Among cultures with gram-positive species, Coagulase-negative Staphylococci
(CONS) (n = 14, 20.3%) predominated. CONS showed high resistance to Oxacillin
(80%), Cefotaxime (66.7%) and Meropenem (80%) but good susceptibility (100%) to
Vancomycin and Linezolid. Prevalence of multidrug-resistant strain was 73.9%.
CONCLUSIONS: Klebsiella species and CONS were the most common causes of neonatal
sepsis in our study. A significant proportion of the isolates were multidrug
resistant strains, which pose a great threat to neonatal survival, and thereby,
warrant modification of existing empirical therapy. Implementation of effective
preventive strategies to combat the emergence of antibiotic resistance is
urgently needed. We recommend a combination of Piperacillin-Tazobactam and
Ofloxacin as the first line therapy and combination of Vancomycin and Meropenem
as the second line empirical therapy in our NICU.
PMID- 29950163
TI - Vonoprazan-based triple therapy is non-inferior to susceptibility-guided proton
pump inhibitor-based triple therapy for Helicobacter pylori eradication.
AB - BACKGROUND: All Helicobacter pylori-infected patients are recommended for
eradication with an appropriate regimen in each geographic area. The choice of
the therapy is somewhat dependent on the antimicrobial susceptibility. The rate
of clarithromycin resistance has been increasing and is associated with failure;
thus, susceptibility testing is recommended before triple therapy with
clarithromycin. However, antimicrobial susceptibility testing is not yet
clinically available and an alternative newly developed acid inhibitor vonoprazan
is used for triple therapy in Japan. The aim of this study was to determine
whether vonoprazan-based triple therapy is plausible treatment in H. pylori
eradication. METHODS: A retrospective observational study of H. pylori
eradication was conducted in a single institute. The patients who requested
antimicrobial susceptibility testing were treated with susceptibility-guided
proton pump inhibitor-based triple therapy in International University of Health
and Welfare Hospital from 2013 to 2016. Other patients were treated with
empirical treatment with a proton pump inhibitor. From 2015 to 2016, vonoprazan
based triple treatment (vonoprazan, 20 mg; amoxicillin, 750 mg; and
clarithromycin, 200 or 400 mg, b.i.d.) was conducted, and its effectiveness was
compared with susceptibility-guided proton pump inhibitor-based triple therapy.
We also investigated the improvement in eradication rate when antimicrobial
susceptibility testing was performed, and compared the outcomes of vonoprazan
based and proton pump inhibitor-based empirical therapy. RESULTS: A total of 1355
patients who received first-line eradication treatment were enrolled in the
present study. The eradication rates of the empirical proton pump inhibitor-based
therapy and the vonoprazan-based therapy group in a per-protocol analysis were
86.3% (95% CI 83.8-88.8) and 97.4% (95% CI 95.7-99.1), respectively. In 212
patients who received antimicrobial susceptibility testing, the rate of
clarithromycin resistant was 23.5% and the eradication rate in susceptibility
guided treatment was 95.7% (95% CI 92.9-98.4). The difference between
susceptibility-guided and vonoprazan-based therapy was - 1.7% (95% CI - 4.9 to
1.5%), and the non-inferiority of vonoprazan-based triple therapy was confirmed.
CONCLUSIONS: Vonoprazan-based triple therapy was effective as susceptibility
guided triple therapy for H. pylori eradication. An empirical triple therapy with
vonoprazan is preferable even in area with high rates of clarithromycin
resistance. Trial registration The study was retrospectively registered in
University Hospital Medical Information Network (UMIN000032351).
PMID- 29950164
TI - Prognostic value of localization of epidermal growth factor receptor in lung
adenocarcinoma.
AB - BACKGROUND: The nuclear translocation of epidermal growth factor receptor (EGFR)
has been considered to play a role in carcinogenesis. However, the relevance of
differentially located EGFR proteins in lung cancer remains unclear. METHODS: We
examined 161 patients with primary lung adenocarcinoma to detect EGFR expression
in lung cancer cells using immunohistochemistry and determined the correlations
of EGFR expression with clinical characteristics, EGFR mutations, and survival
time. Moreover, we graded complete membranous staining with strong intensity as
high membranous EGFR (mEGFR) expression, and nuclear EGFR staining with strong
intensity as high nuclear (nEGFR) expression. RESULTS: The prevalence of high
mEGFR and nEGFR expression in lung adenocarcinoma was 42.86 and 39.13%,
respectively. After multivariate analyses, high mEGFR expression was associated
with a significantly reduced mortality risk in older patients, those with a
history of smoking, and those without brain metastasis (hazard ratio[95%
confidential interval], HR[95% CI] = 0.55[0.32~ 0.92]; 0.51[0.26~ 0.98] and
0.56[0.33~ 0.94], in overall survival, respectively). An association between high
nEGFR expression and early recurrence was observed in patients with metastasis
(HR[95% CI] =1.68[1.05~ 2.68], in progression-free survival). Notably, patients
with low mEGFR and low nEGFR expression had the lowest survival rate in cases
without brain metastasis (p = 0.018) and with a history of smoking (p = 0.062)
and total EGFR (any high mEGFR or nEGFR) expression indicated a more favorable
response to platinum-based chemotherapy regardless of EGFR mutations (HR[95% CI]
=0.33[0.12-0.92]; adjusted HR[95% CI] = 0.36[0.13~ 1.02] with the use of tyrosine
kinase inhibitor). CONCLUSIONS: EGFR proteins at different cellular locations in
lung adenocarcinoma might influence the biology of cancer cells and are an
independent indicator of more favorable prognosis and treatment response.
PMID- 29950165
TI - HmmUFOtu: An HMM and phylogenetic placement based ultra-fast taxonomic assignment
and OTU picking tool for microbiome amplicon sequencing studies.
AB - Culture-independent analysis of microbial communities frequently relies on
amplification and sequencing of the prokaryotic 16S ribosomal RNA gene. Typical
analysis pipelines group sequences into operational taxonomic units (OTUs) to
infer taxonomic and phylogenetic relationships. Here, we present HmmUFOtu, a
novel tool for processing microbiome amplicon sequencing data, which performs
rapid per-read phylogenetic placement, followed by phylogenetically informed
clustering into OTUs and taxonomy assignment. Compared to standard pipelines,
HmmUFOtu more accurately and reliably recapitulates microbial community diversity
and composition in simulated and real datasets without relying on heuristics or
sacrificing speed or accuracy.
PMID- 29950166
TI - Development of an occupational advice intervention for patients undergoing lower
limb arthroplasty (the OPAL study).
AB - BACKGROUND: There are an increasing number of patients of working age undergoing
hip and knee replacements. Currently there is variation in the advice and support
given about sickness absence, recovery to usual activities and return to work
after these procedures. Earlier, sustainable, return to work improves the health
of patients and benefits their employers and society. An intervention that
encourages and supports early recovery to usual activities, including work, has
the potential to reduce the health and socioeconomic burden of hip and knee
replacements. METHODS/DESIGN: A two-phase research programme delivered over 27
months will be used to develop and subsequently test the feasibility of an
occupational advice intervention to facilitate return to work and usual
activities in patients undergoing lower limb arthroplasty. The 2 phases will
incorporate a six-stage intervention mapping process: Phase 1: Intervention
mapping stages 1-3: 1 Needs assessment (including rapid evidence synthesis,
prospective cohort analysis and structured stakeholder interviews) 2
Identification of intended outcomes and performance objectives 3 Selection of
theory-based methods and practical strategies Phase 2: Intervention mapping
stages 4-6: 4 Development of components and materials for the occupational advice
intervention using a modified Delphi process 5 Adoption and implementation of the
intervention 6 Evaluation and feasibility testing The study will be undertaken in
four National Health Service (NHS) hospitals in the United Kingdom and two Higher
Education Institutions. DISCUSSION: OPAL (Occupational advice for Patients
undergoing Arthroplasty of the Lower limb) aims to develop an occupational advice
intervention to support early recovery to usual activities including work, which
is tailored to the requirements of patients undergoing hip and knee replacements.
The developed intervention will then be assessed with a specific focus on
evaluating its feasibility as a potential trial intervention to improve speed of
recovery to usual activities including work. TRIAL REGISTRATION: The study was
registered retrospectively with the International Standard Randomised Controlled
Trials Number (ISRCTN): 27426982 (Date 20/12/2016) and the International
prospective register of systematic reviews (PROSPERO): CRD42016045235 (Date
04/08/2016).
PMID- 29950167
TI - Does citation matter? Research citation in policy documents as an indicator of
research impact - an Australian obesity policy case-study.
AB - BACKGROUND: Citation of research in policy documents has been suggested as an
indicator of the potential longer-term impacts of research. We investigated the
use of research citations in childhood obesity prevention policy documents from
New South Wales (NSW), Australia, considering the feasibility and value of using
research citation as a proxy measure of research impact. METHODS: We examined
childhood obesity policy documents produced between 2000 and 2015, extracting
childhood obesity-related references and coding these according to reference
type, geographical origin and type of research. A content analysis of the policy
documents examined where and how research was cited in the documents and the
context of citation for individual research publications. RESULTS: Over a quarter
(28%) of the policy documents (n = 86) were not publicly available, almost two
thirds (63%) contained references, half (47%) cited obesity-related research and
over a third (41%) of those containing references used unorthodox referencing
styles, making reference extraction laborious. No patterns, in terms of the types
of documents more likely to cite research, were observed and the number of
obesity research publications cited per document was highly variable. In total,
263 peer-reviewed and 94 non-peer-reviewed obesity research publications were
cited. Research was most commonly cited to support a policy argument or choice of
solution. However, it was not always possible to determine how or why individual
publications were cited or whether the cited research itself had influenced the
policy process. Content analysis identified circumstances where research was
mentioned or considered, but not directly cited. CONCLUSIONS: Citation of
research in policy documents in this case did not always provide evidence that
the cited research had influenced the policy process, only that it was accessible
and relevant to the content of the policy document. Research citation across
these public health policy documents varied greatly and is unlikely to be an
accurate reflection of actual research use by the policy agencies involved. The
links between citation and impact may be more easily drawn in specific policy
areas or types of documents (e.g. clinical guidelines), where research appraisal
feeds directly into policy recommendations.
PMID- 29950168
TI - Rare variability in adrenoleukodystrophy: a case report.
AB - BACKGROUND: X-linked adrenoleukodystrophy is a genetic disorder with diverse
clinical phenotypes. Of these phenotypes, the cerebral form usually manifests
during early childhood with rapid cognitive and neurological deterioration and is
accompanied by extensive white matter involvement. Adrenomyeloneuropathy,
however, usually affects young adults and has focal symptoms typical of spinal
cord and peripheral nerve involvement. CASE PRESENTATION: A 35-year-old African
American man with a history of alcohol abuse presented with personality changes
and lower extremity weakness. Diffuse demyelination was found on the brain image,
and a diagnosis of the cerebral form was made based on the clinical features and
genetic test. CONCLUSIONS: We report a rare case of adult-onset cerebral X-linked
leukodystrophy with a clinical phenotype of adrenomyeloneuropathy, and the
diagnosis was confounded by a history of alcohol abuse.
PMID- 29950169
TI - An attempt at modeling COPD epidemiological trends in France.
AB - BACKGROUND: Anticipating the future burden of chronic obstructive pulmonary
disease (COPD) is required to develop adequate public health policies. METHODS: A
dynamic population model was built to estimate COPD prevalence by 2025 using data
collected during the most recent large general population study on COPD
prevalence in France (2005) as baseline values. Sensitivity analyses were
performed to test the effect of variations in key input variables. RESULTS: The
model predicted a steady increase in crude COPD prevalence among subjects
aged>=45 years from 2005 (prevalence estimate: 84.510/00) to 2025 (projected
prevalence: 95.760/00, + 0.560/00/yr). There was a 4-fold increase in the
prevalence of GOLD grade 3-4 cases, a 23% relative increase in women and a 21%
relative increase in subjects >=75 years. In sensitivity analyses, these temporal
trends were robust. Factors associated with > 5% relative variations in projected
2025 prevalence estimates were baseline prevalence and severity distribution,
incidence in women and severity of incident cases, transition rates between
severity grades, and mortality. CONCLUSIONS: Projections of future COPD
epidemiology consistently predict an increase in the prevalence of moderate-to
very severe COPD, especially due to increases among women and subjects aged >=75
years. Developing robust prediction models requires collecting reliable data on
current COPD epidemiology.
PMID- 29950170
TI - Evaluating parents' decisions about next-generation sequencing for their child in
the NC NEXUS (North Carolina Newborn Exome Sequencing for Universal Screening)
study: a randomized controlled trial protocol.
AB - BACKGROUND: Using next-generation sequencing (NGS) in newborn screening (NBS)
could expand the number of genetic conditions detected pre-symptomatically,
simultaneously challenging current precedents, raising ethical concerns, and
extending the role of parental decision-making in NBS. The NC NEXUS (Newborn
Exome Sequencing for Universal Screening) study seeks to assess the technical
possibilities and limitations of NGS-NBS, devise and evaluate a framework to
convey various types of genetic information, and develop best practices for
incorporating NGS-NBS into clinical care. The study is enrolling both a healthy
cohort and a cohort diagnosed with known disorders identified through recent
routine NBS. It uses a novel age-based metric to categorize a priori the large
amount of data generated by NGS-NBS and interactive online decision aids to guide
parental decision-making. Primary outcomes include: (1) assessment of NGS-NBS
sensitivity, (2) decision regret, and (3) parental decision-making about NGS-NBS,
and, for parents randomized to have the option of requesting them, additional
findings (diagnosed and healthy cohorts). Secondary outcomes assess parents'
reactions to the study and to decision-making. METHODS/DESIGN: Participants are
parents and children in a well-child cohort recruited from a prenatal clinic and
a diagnosed cohort recruited from pediatric clinics that treat children with
disorders diagnosed through traditional NBS (goal of 200 children in each
cohort). In phase 1, all parent participants use an online decision aid to decide
whether to accept NGS-NBS for their child and provide consent for NGS-NBS. In
phase 2, parents who consent to NGS-NBS are randomized to a decision arm or
control arm (2:1 allocation) and learn their child's NGS-NBS results, which
include conditions from standard (non-NGS) NBS plus other highly actionable
childhood-onset conditions. Parents in the decision arm use a second decision aid
to make decisions about additional results from their child's sequencing. In
phase 3, decision arm participants learn additional results they have requested.
Online questionnaires are administered at up to five time points. DISCUSSION: NC
NEXUS will use a rigorous interdisciplinary approach designed to collect rich
data to inform policy, practice, and future research. TRIAL REGISTRATION:
clinicaltrials.gov, NCT02826694 . Registered on 11 July, 2016.
PMID- 29950171
TI - Determinants and perceptions of the utilization of tetanus toxoid immunization
among reproductive-age women in Dukem Town, Eastern Ethiopia: a community-based
cross-sectional study.
AB - BACKGROUND: Maternal and neonatal tetanus (MNT) is still the major public health
problem in about 25 countries, mainly in Africa and Asia. However, the
utilization of intervention strategies, like tetanus toxoid (TT) immunization
remains low in these countries. In Ethiopia, only 49% of the pregnant mothers
received TT2+ in 2016. This study was designed to evaluate perceptions and
factors affecting the utilization of TT immunization among reproductive-age women
in Dukem town, Eastern Ethiopia, 2016. METHODS: We conducted a community-based
cross-sectional study from May to October 2016. A simple random sampling method
was employed to select samples of 422 women. Data were collected using a,
pretested semi-structured and a face-to-face interviewer-administered
questionnaire. We entered data in to Epi Info version 7 and analyzed them by SPSS
version 20 software. Odds ratios and a 95% CI at 0 < 0.05 p-value were calculated
to ascertain the significance of associations. RESULTS: Response rate was 98.6%
(N = 416). Mean age with standard deviation was 29.25+/- 5.11 years, and average
family size was 4.19. Our study showed the utilization of TT immunization was
39.2% (N = 163). Of the participants, 33.9% (N = 141) had never been vaccinated.
ANC follow up service [AOR: 2.56, 95% CI: (1.18, 5.49)], distance from health
facilities [AOR: 2.27, 95% CI: (1.27, 4.09)], knowing vaccination date [AOR:
1.98, 95% CI: (1.23, 3.18)], having a TV set in the house [AOR: 1.80, 95% CI:
(1.11, 2.917)], maternal education [AOR: 1.41, 95% CI: (1.84, 2.30), and place of
delivery [AOR: 1.19, 95% CI: (1.00, 1.43)] were factors significantly associated
with the utilization of TT immunization. CONCLUSIONS: This study indicated the
utilization of TT immunization was low. ANC service follow up, distance from
health facilities, knowing vaccination date, having a TV in the house, mothers'
educational status, and place of delivery were significant predictors. Our study
suggests that policymakers and other stakeholders should consider the need for
increasing access to maternal education, like basic adult education, ANC follow
up services, providing accessible health facilities, improving varieties of
communication media, promoting female occupational status, and providing
appropriate vaccination cards.
PMID- 29950172
TI - Disease-specific regulation of gene expression in a comparative analysis of
juvenile idiopathic arthritis and inflammatory bowel disease.
AB - BACKGROUND: The genetic and immunological factors that contribute to differences
in susceptibility and progression between sub-types of inflammatory and
autoimmune diseases continue to be elucidated. Inflammatory bowel disease and
juvenile idiopathic arthritis are both clinically heterogeneous and known to be
due in part to abnormal regulation of gene activity in diverse immune cell types.
Comparative genomic analysis of these conditions is expected to reveal
differences in underlying genetic mechanisms of disease. METHODS: We performed
RNA-Seq on whole blood samples from 202 patients with oligoarticular,
polyarticular, or systemic juvenile idiopathic arthritis, or with Crohn's disease
or ulcerative colitis, as well as healthy controls, to characterize differences
in gene expression. Gene ontology analysis combined with Blood Transcript Module
and Blood Informative Transcript analysis was used to infer immunological
differences. Comparative expression quantitative trait locus (eQTL) analysis was
used to quantify disease-specific regulation of transcript abundance. RESULTS: A
pattern of differentially expressed genes and pathways reveals a gradient of
disease spanning from healthy controls to oligoarticular, polyarticular, and
systemic juvenile idiopathic arthritis (JIA); Crohn's disease; and ulcerative
colitis. Transcriptional risk scores also provide good discrimination of
controls, JIA, and IBD. Most eQTL are found to have similar effects across
disease sub-types, but we also identify disease-specific eQTL at loci associated
with disease by GWAS. CONCLUSION: JIA and IBD are characterized by divergent
peripheral blood transcriptomes, the genetic regulation of which displays limited
disease specificity, implying that disease-specific genetic influences are
largely independent of, or downstream of, eQTL effects.
PMID- 29950173
TI - Production of a human milk oligosaccharide 2'-fucosyllactose by metabolically
engineered Saccharomyces cerevisiae.
AB - BACKGROUND: 2'-Fucosyllactose (2-FL), one of the most abundant oligosaccharides
in human milk, has potential applications in foods due to its health benefits
such as the selective promotion of bifidobacterial growth and the inhibition of
pathogenic microbial binding to the human gut. Owing to the limited amounts of 2
FL in human milk, alternative microbial production of 2-FL is considered
promising. To date, microbial production of 2-FL has been studied mostly in
Escherichia coli. In this study, 2-FL was produced alternatively by using a yeast
Saccharomyces cerevisiae, which may have advantages over E. coli. RESULTS: Fucose
and lactose were used as the substrates for the salvage pathway which was
constructed with fkp coding for a bifunctional enzyme exhibiting L-fucokinase and
guanosine 5'-diphosphate-L-fucose phosphorylase activities, fucT2 coding for
alpha-1,2-fucosyltransferase, and LAC12 coding for lactose permease. Production
of 2-FL by the resulting engineered yeast was verified by mass spectrometry. 2-FL
titers of 92 and 503 mg/L were achieved from 48-h batch fermentation and 120-h
fed-batch fermentation fed with ethanol as a carbon source, respectively.
CONCLUSIONS: This is the first report on 2-FL production by using yeast S.
cerevisiae. These results suggest that S. cerevisiae can be considered as a host
engineered for producing 2-FL via the salvage pathway.
PMID- 29950174
TI - Innovation in neglected tropical disease drug discovery and development.
AB - BACKGROUND: Neglected tropical diseases (NTDs) are closely related to poverty and
affect over a billion people in developing countries. The unmet treatment needs
cause high mortality and disability thereby imposing a huge burden with severe
social and economic consequences. Although coordinated by the World Health
Organization, various philanthropic organizations, national governments and the
pharmaceutical industry have been making efforts in improving the situation, the
control of NTDs is still inadequate and extremely difficult today. The lack of
safe, effective and affordable medicines is a key contributing factor. This paper
reviews the recent advances and some of the challenges that we are facing in the
fight against NTDs. MAIN BODY: In recent years, a number of innovations have
demonstrated propensity to promote drug discovery and development for NTDs.
Implementation of multilateral collaborations leads to continued efforts and
plays a crucial role in drug discovery. Proactive approaches and advanced
technologies are urgently needed in drug innovation for NTDs. However, the
control and elimination of NTDs remain a formidable task as it requires
persistent international cooperation to make sustainable progresses for a long
period of time. Some currently employed strategies were proposed and verified to
be successful, which involve both mechanisms of 'Push' which aims at cutting the
cost of research and development for industry and 'Pull' which aims at increasing
market attractiveness. Coupled to this effort should be the exercise of shared
responsibility globally to reduce risks, overcome obstacles and maximize
benefits. Since NTDs are closely associated with poverty, it is absolutely
essential that the stakeholders take concerted and long-term measures to meet
multifaceted challenges by alleviating extreme poverty, strengthening social
intervention, adapting climate changes, providing effective monitoring and
ensuring timely delivery. CONCLUSIONS: The ongoing endeavor at the global scale
will ultimately benefit the patients, the countries they are living and,
hopefully, the manufacturers who provide new preventive, diagnostic and
therapeutic products.
PMID- 29950176
TI - Genomic surveillance of avian-origin influenza A viruses causing human disease.
AB - Avian influenza A viruses (AIVs) pose a threat to global health because of their
sporadic zoonotic transmission and potential to cause pandemics. Genomic
surveillance of AIVs has become a powerful, cost-effective approach for studying
virus transmission, evolution, and dissemination, and has the potential to inform
outbreak control efforts and policies.
PMID- 29950175
TI - Sex differences in body composition and association with cardiometabolic risk.
AB - BACKGROUND: Body composition differs between men and women, with women having
proportionally more fat mass and men more muscle mass. Although men and women are
both susceptible to obesity, health consequences differ between the sexes. The
purpose of our study was to assess sex differences in body composition using
anatomic and functional imaging techniques, and its relationship to
cardiometabolic risk markers in subjects with overweight/obesity. METHODS: After
written informed consent, we prospectively recruited 208 subjects with
overweight/obesity who were otherwise healthy (94 men, 114 women, age 37 +/- 10
years, BMI 35 +/- 6 kg/m2). Subjects underwent dual-energy X-ray absorptiometry
(DXA) and computed tomography (CT) for fat and muscle mass, proton MR
spectroscopy (1H-MRS) for intrahepatic (IHL) and intramyocellular lipids (IMCL),
an oral glucose tolerance test, serum insulin, lipids, and inflammatory markers.
Men and women were compared by Wilcoxon signed rank test. Linear correlation and
multivariate analyses between body composition and cardiometabolic risk markers
were performed. RESULTS: Women and men were of similar mean age and BMI (p >=
0.2). Women had higher %fat mass, extremity fat, and lower lean mass compared to
men (p <= 0.0005). However, men had higher visceral adipose tissue (VAT) and IMCL
and higher age-and BMI-adjusted IHL (p < 0.05). At similar age and BMI, men had a
more detrimental cardiometabolic risk profile compared to women (p < 0.01).
However, VAT in women, and IMCL in men, were more strongly associated with
cardiometabolic risk markers, while more lower extremity fat was associated with
a more favorable cardiometabolic profile in women compared to men (p <= 0.03).
CONCLUSIONS: Although the male pattern of fat distribution is associated with a
more detrimental cardiometabolic risk profile compared to women of similar age
and BMI, VAT is more strongly associated with cardiometabolic risk markers in
women, while IMCL are more detrimental in men. Lower extremity fat is relatively
protective, in women more than in men. This suggests that detailed anatomic and
functional imaging, rather than BMI, provides a more complete understanding of
metabolic risk associated with sex differences in fat distribution.
PMID- 29950177
TI - Two-center clinical validation and quantitative assessment of respiratory
triggered retrospectively cardiac gated balanced-SSFP cine cardiovascular
magnetic resonance imaging in adults.
AB - BACKGROUND: Breath-hold (BH) requirement remains the limiting factor on the
spatio-temporal resolution and coverage of the cine balanced steady-state free
precession (bSSFP) cardiovascular magnetic resonance (CMR) imaging. In this
prospective two-center clinical trial, we validated the performance of a
respiratory triggered (RT) bSSFP cine sequence for evaluation of biventricular
function. METHODS: Our study included 23 asymptomatic healthy subjects and 60
consecutive patients from Institute A (n = 39) and Institute B (n = 21) referred
for a clinically indicated CMR study. We implemented a RT sequence with a
respiratory synchronized drive to steady state (SS) of bSSFP signal, before the
commencement of image data acquisition with prospective cardiac arrhythmia
rejection and retrospectively cardiac gated reconstruction in real-time. Left
(LV) and right (RV) ventricular function and LV mass were evaluated by using RT
bSSFP and conventional BH-bSSFP sequences with one cardiac cycle for SS
preparation keeping all the imaging parameters identical. The performance of the
sequences was evaluated by using quantitative and semi-quantitative metrics.
RESULTS: Global LV and RV functional parameters and LV mass obtained from the RT
bSSFP and BH-bSSFP sequences were in good agreement. Quantitative metrics
designed to capture fluctuation in SS signal intensity showed no significant
difference between sequences. In addition, blood-to-myocardial contrast was
nearly identical between sequences. The combined clinical score for image quality
was excellent or good for 100% of cases with the BH-bSSFP and 83% of cases with
the RT-bSSFP sequence. The de facto image acquisition time for RT-bSSFP was
statistically significantly longer than that for conventional BH-bSSFP (7.9 +/-
3.4 min vs. 5.1 +/- 2.6 min). CONCLUSIONS: Cine RT-bSSFP is an alternative for
evaluating global biventricular function with contrast and spatio-temporal
resolutions that are similar to those attained by using the BH-bSSFP sequence,
albeit with a modest time penalty and a small reduction in image quality.
PMID- 29950178
TI - Importance of standardizing timing of hematocrit measurement when using
cardiovascular magnetic resonance to calculate myocardial extracellular volume
(ECV) based on pre- and post-contrast T1 mapping.
AB - BACKGROUND: Cardiovascular magnetic resonance (CMR) can be used to calculate
myocardial extracellular volume fraction (ECV) by relating the longitudinal
relaxation rate in blood and myocardium before and after contrast-injection to
hematocrit (Hct) in blood. Hematocrit is known to vary with body posture, which
could affect the calculations of ECV. The aim of this study was to test the
hypothesis that there is a significant increase in calculated ECV values if the
Hct is sampled after the CMR examination in supine position compared to when the
patient arrives at the MR department. METHODS: Forty-three consecutive patients
including various pathologies as well as normal findings were included in the
study. Venous blood samples were drawn upon arrival to the MR department and
directly after the examination with the patient remaining in supine position. A
Modified Look-Locker Inversion recovery (MOLLI) protocol was used to acquire mid
ventricular short-axis images before and after contrast injection from which
motion-corrected T1 maps were derived and ECV was calculated. RESULTS: Hematocrit
decreased from 44.0 +/- 3.7% before to 40.6 +/- 4.0% after the CMR examination (p
< 0.001). This resulted in a change in calculated ECV from 24.7 +/- 3.8% before
to 26.2 +/- 4.2% after the CMR examination (p < 0.001). All patients decreased in
Hct after the CMR examination compared to before except for two patients whose
Hct remained the same. CONCLUSION: Variability in CMR-derived myocardial ECV can
be reduced by standardizing the timing of Hct measurement relative to the CMR
examination. Thus, a standardized acquisition of blood sample for Hct after the
CMR examination, when the patient is still in supine position, would increase the
precision of ECV measurements.
PMID- 29950179
TI - Isolation and identification of Asaia sp. in Anopheles spp. mosquitoes collected
from Iranian malaria settings: steps toward applying paratransgenic tools against
malaria.
AB - BACKGROUND: In recent years, the genus Asaia (Rhodospirillales: Acetobacteraceae)
has been isolated from different Anopheles species and presented as a promising
tool to combat malaria. This bacterium has unique features such as presence in
different organs of mosquitoes (midgut, salivary glands and reproductive organs)
of female and male mosquitoes and vertical and horizontal transmission. These
specifications lead to the possibility of introducing Asaia as a robust candidate
for malaria vector control via paratransgenesis technology. Several studies have
been performed on the microbiota of Anopheles mosquitoes (Diptera: Culicidae) in
Iran and the Middle East to find a suitable candidate for controlling the malaria
based on paratransgenesis approaches. The present study is the first report of
isolation, biochemical and molecular characterization of the genus Asaia within
five different Anopheles species which originated from different zoogeographical
zones in the south, east, and north of Iran. METHODS: Mosquitoes originated from
field-collected and laboratory-reared colonies of five Anopheles spp. Adult
mosquitoes were anesthetized; their midguts were isolated by dissection, followed
by grinding the midgut contents which were then cultured in enrichment broth
media and later in CaCO3 agar plates separately. Morphological, biochemical and
physiological characterization were carried out after the appearance of colonies.
For molecular confirmation, selected colonies were cultured, their DNAs were
extracted and PCR was performed on the 16S ribosomal RNA gene using specific
newly designed primers. RESULTS: Morphological, biochemical, physiological and
molecular results indicated that all isolates are members of the genus Asaia.
CONCLUSIONS: Contrary to previous opinions, our findings show that Asaia bacteria
are present in both insectary-reared colonies and field-collected mosquitoes and
can be isolated by simple and specific methods. Furthermore, with respect to the
fact that we isolated Asaia within the different Anopheles specimens from
distinct climatic and zoogeographical regions, it is promising and may be
concluded that species of this genus can tolerate the complicated environmental
conditions of the vector-borne diseases endemic regions. Therefore, it can be
considered as a promising target in paratransgenesis and vector control programs.
However, we suggest that introducing the new technologies such as next generation
sequencing and robust in silico approaches may pave the way to find a unique
biomarker for rapid and reliable differentiation of the Asaia species.
PMID- 29950182
TI - Effects of pre-transplant azithromycin administration on kidney graft function:
study protocol for a double-blind randomized clinical trial.
AB - BACKGROUND: Kidney transplantation is the best strategy for the management of end
stage renal disease; however, the outcomes need to improve further. Macrolides
show antimicrobial and anti-inflammatory properties in chronic diseases and
intraoperatively, and can accumulate in tissues for extended periods. Therefore,
theoretically, when administered to a donor and because of accumulation in the
donor kidney, macrolides can cause graft immunomodulation and improve kidney
transplantation outcomes. METHODS: This study is a single-center, randomized
clinical trial. A total of 60 kidney donors will be randomly allocated to the
azithromycin or placebo group and treated with a single dose (1 g) of
azithromycin or placebo, respectively, 1 day before surgery. Recruitment
commenced in September 2016 and is expected to be completed by March 2018. The
primary outcome is kidney graft function. The secondary outcomes include
rejection rate, urinary tract infections in graft recipients, pain and systemic
inflammatory response syndrome in live donors, and complications in both donors
and recipients. Outcomes will be evaluated at baseline and every day in the first
week after transplantation, as well as at 1 and 3 months post transplantation.
Adverse reactions will be documented. If the efficacy of azithromycin in reducing
adverse outcomes is confirmed, it would serve as an easy to use, economic
intervention able to lower post-transplantation risks. DISCUSSION: Short and mid
term analyses of blood and urine samples as well as immunological assays will
facilitate a more in-depth analysis of the effects of azithromycin on
transplantation outcomes. TRIAL REGISTRATION: Iranian Clinical Trial Registry,
IRCT201606141853N11 , registered on September 5, 2016.
PMID- 29950180
TI - Therapy-induced stress response is associated with downregulation of pre-mRNA
splicing in cancer cells.
AB - BACKGROUND: Abnormal pre-mRNA splicing regulation is common in cancer, but the
effects of chemotherapy on this process remain unclear. METHODS: To evaluate the
effect of chemotherapy on slicing regulation, we performed meta-analyses of
previously published transcriptomic, proteomic, phosphoproteomic, and secretome
datasets. Our findings were verified by LC-MS/MS, western blotting,
immunofluorescence, and FACS analyses of multiple cancer cell lines treated with
cisplatin and pladienolide B. RESULTS: Our results revealed that different types
of chemotherapy lead to similar changes in alternative splicing by inducing
intron retention in multiple genes. To determine the mechanism underlying this
effect, we analyzed gene expression in 101 cell lines affected by gamma
irradiation, hypoxia, and 10 various chemotherapeutic drugs. Strikingly, only
genes involved in the cell cycle and pre-mRNA splicing regulation were changed in
a similar manner in all 335 tested samples regardless of stress stimuli. We
revealed significant downregulation of gene expression levels in these two
pathways, which could be explained by the observed decrease in splicing
efficiency and global intron retention. We showed that the levels of active
spliceosomal proteins might be further post-translationally decreased by
phosphorylation and export into the extracellular space. To further explore these
bioinformatics findings, we performed proteomic analysis of cisplatin-treated
ovarian cancer cells. Finally, we demonstrated that the splicing inhibitor
pladienolide B impairs the cellular response to DNA damage and significantly
increases the sensitivity of cancer cells to chemotherapy. CONCLUSIONS: Decreased
splicing efficiency and global intron retention is a novel stress response
mechanism that may promote survival of malignant cells following therapy. We
found that this mechanism can be inhibited by pladienolide B, which significantly
increases the sensitivity of cancer cells to cisplatin which makes it a good
candidate drug for improving the efficiency of cancer therapy.
PMID- 29950184
TI - A predictive model for conversion to psychosis in clinical high-risk patients.
AB - BACKGROUND: The authors developed a practical and clinically useful model to
predict the risk of psychosis that utilizes clinical characteristics empirically
demonstrated to be strong predictors of conversion to psychosis in clinical high
risk (CHR) individuals. The model is based upon the Structured Interview for
Psychosis Risk Syndromes (SIPS) and accompanying clinical interview, and yields
scores indicating one's risk of conversion. METHODS: Baseline data, including
demographic and clinical characteristics measured by the SIPS, were obtained on
199 CHR individuals seeking evaluation in the early detection and intervention
for mental disorders program at the New York State Psychiatric Institute at
Columbia University Medical Center. Each patient was followed for up to 2 years
or until they developed a syndromal DSM-4 disorder. A LASSO logistic fitting
procedure was used to construct a model for conversion specifically to a
psychotic disorder. RESULTS: At 2 years, 64 patients (32.2%) converted to a
psychotic disorder. The top five variables with relatively large standardized
effect sizes included SIPS subscales of visual perceptual abnormalities,
dysphoric mood, unusual thought content, disorganized communication, and violent
ideation. The concordance index (c-index) was 0.73, indicating a moderately
strong ability to discriminate between converters and non-converters.
CONCLUSIONS: The prediction model performed well in classifying converters and
non-converters and revealed SIPS measures that are relatively strong predictors
of conversion, comparable with the risk calculator published by NAPLS (c-index =
0.71), but requiring only a structured clinical interview. Future work will seek
to externally validate the model and enhance its performance with the
incorporation of relevant biomarkers.
PMID- 29950185
TI - Centers for medicare and medicaid services hospital-acquired conditions policy
for central line-associated bloodstream infection (CLABSI) and cather-associated
urinary tract infection (CAUTI) shows minimal impact on hospital reimbursement.
AB - OBJECTIVE: In 2008, the Centers for Medicare and Medicaid Services (CMS) stopped
reimbursing for hospital-acquired conditions (HACs) not present on admission
(POA). We sought to understand why this policy did not impact central line
associated bloodstream infection (CLABSI) and catheter-associated urinary tract
infection (CAUTI) trends. DESIGN: Retrospective cohort study. SETTING: Acute-care
hospitals in the United States.ParticipantsFee-for-service Medicare patients
discharged January 1, 2007, through December 31, 2011. METHODS: Using inpatient
Medicare claims data, we analyzed billing practices before and after the HAC
policy was implemented, including the use and POA designation of codes for CLABSI
or CAUTI. For the 3-year period following policy implementation, we determined
the impact on diagnosis-related groups (DRG) determining reimbursement as well as
hospital characteristics associated with the reimbursement impact. RESULTS:
During the study period, 65,205,607 Medicare fee-for-service hospitalizations
occurred at 3,291 acute-care, nonfederal US hospitals. Based on coding, CLABSI
and CAUTI affected 0.23% and 0.06% of these hospitalizations, respectively. In
addition, following the HAC policy, 82% of the CLABSI codes and 91% of the CAUTI
codes were marked POA, which represented a large increase in the use of this
designation. Finally, for the small numbers of CLABSI and CAUTI coded as not POA,
financial impacts were detected on only 0.4% of the hospitalizations with a
CLABSI code and 5.7% with a CAUTI code. CONCLUSIONS: Part of the reason the HAC
policy did not have its intended impact is that billing codes for CLABSI and
CAUTI were rarely used, were commonly listed as POA in the postpolicy period, and
infrequently impacted hospital reimbursement.
PMID- 29950183
TI - Post-translational buffering leads to convergent protein expression levels
between primates.
AB - BACKGROUND: Differences in gene regulation between human and closely related
species influence phenotypes that are distinctly human. While gene regulation is
a multi-step process, the majority of research concerning divergence in gene
regulation among primates has focused on transcription. RESULTS: To gain a
comprehensive view of gene regulation, we surveyed genome-wide ribosome
occupancy, which reflects levels of protein translation, in lymphoblastoid cell
lines derived from human, chimpanzee, and rhesus macaque. We further integrated
messenger RNA and protein level measurements collected from matching cell lines.
We find that, in addition to transcriptional regulation, the major factor
determining protein level divergence between human and closely related species is
post-translational buffering. Inter-species divergence in transcription is
generally propagated to the level of protein translation. In contrast, gene
expression divergence is often attenuated post-translationally, potentially
mediated through post-translational modifications. CONCLUSIONS: Results from our
analysis indicate that post-translational buffering is a conserved mechanism that
led to relaxation of selective constraint on transcript levels in humans.
PMID- 29950181
TI - Comparison of village dog and wolf genomes highlights the role of the neural
crest in dog domestication.
AB - BACKGROUND: Domesticated from gray wolves between 10 and 40 kya in Eurasia, dogs
display a vast array of phenotypes that differ from their ancestors, yet mirror
other domesticated animal species, a phenomenon known as the domestication
syndrome. Here, we use signatures persisting in dog genomes to identify genes and
pathways possibly altered by the selective pressures of domestication. RESULTS:
Whole-genome SNP analyses of 43 globally distributed village dogs and 10 wolves
differentiated signatures resulting from domestication rather than breed
formation. We identified 246 candidate domestication regions containing 10.8 Mb
of genome sequence and 429 genes. The regions share haplotypes with ancient dogs,
suggesting that the detected signals are not the result of recent selection. Gene
enrichments highlight numerous genes linked to neural crest and central nervous
system development as well as neurological function. Read depth analysis suggests
that copy number variation played a minor role in dog domestication. CONCLUSIONS:
Our results identify genes that act early in embryogenesis and can confer
phenotypes distinguishing domesticated dogs from wolves, such as tameness,
smaller jaws, floppy ears, and diminished craniofacial development as the targets
of selection during domestication. These differences reflect the phenotypes of
the domestication syndrome, which can be explained by alterations in the
migration or activity of neural crest cells during development. We propose that
initial selection during early dog domestication was for behavior, a trait
influenced by genes which act in the neural crest, which secondarily gave rise to
the phenotypes of modern dogs.
PMID- 29950186
TI - Labour market marginalisation in obsessive-compulsive disorder: a nationwide
register-based sibling control study.
AB - BACKGROUND: The impact of obsessive-compulsive disorder (OCD) on objective
indicators of labour market marginalisation has not been quantified. METHODS:
Linking various Swedish national registers, we estimated the risk of three labour
market marginalisation outcomes (receipt of newly granted disability pension,
long-term sickness absence and long-term unemployment) in individuals diagnosed
with OCD between 2001 and 2013 who were between 16 and 64 years old at the date
of the first OCD diagnosis (n = 16 267), compared with matched general population
controls (n = 157 176). Hazard ratios (HR) with 95% confidence intervals (CI)
were calculated using Cox regression models, adjusting for a number of covariates
(e.g. somatic disorders) and stratifying by sex. To adjust for potential familial
confounders, we further analysed data from 7905 families that included full
siblings discordant for OCD. RESULTS: Patients were more likely to receive at
least one outcome of interest [adjusted HR = 3.63 (95% CI 3.53-3.74)], including
disability pension [adjusted HR = 16.36 (95% CI 15.34-17.45)], being on long-term
sickness absence [adjusted HR = 3.07 (95% CI 2.95-3.19)] and being on long-term
unemployment [adjusted HR = 1.72 (95% CI 1.63-1.82)]. Results remained similar in
the adjusted sibling comparison models. Exclusion of comorbid psychiatric
disorders had a minimal impact on the results. CONCLUSIONS: Help-seeking
individuals with OCD diagnosed in specialist care experience marked difficulties
to participate in the labour market. The findings emphasise the need for
cooperation between policy-makers, vocational rehabilitation and mental health
services in order to design and implement specific strategies aimed at improving
the patients' participation in the labour market.
PMID- 29950187
TI - Performance of the commercially available SERION ELISA classic Echinococcus IgG
test for the detection of cystic echinococcosis in clinical practice.
AB - Diagnosis of cystic echinococcosis (CE) is at present mainly based on imaging
techniques. Serology has a complementary role, partly due to the small number of
standardized and commercially available assays. Therefore we examined the
clinical performance of the SERION ELISA classic Echinococcus IgG test. Using 10
U/ml as a cut-off point, and serum samples from 50 CE patients and 105 healthy
controls, the sensitivity and specificity were 98.0% and 96.2%, respectively. If
patients with other infectious diseases were used as negative controls, the
specificity decreased to 76.9%, which causes poor positive predictive values.
However, if results between 10 and 15 U/ml are classified as indecisive, the
specificity of positive results (>=15 U/ml) increased to 92.5% without greatly
affecting the sensitivity (92.0%). Using this approach in combination with
imaging studies, the SERION ELISA classic Echinococcosis IgG test can be a useful
aid in the diagnosis of CE.
PMID- 29950188
TI - Improved rates of antimicrobial stewardship interventions following
implementation of the Epic antimicrobial stewardship module.
AB - We evaluated the impact of the Epic antimicrobial stewardship module (EAM) on the
number of interventions, antimicrobial usage, and clinical outcomes. Use of the
EAM allowed us to significantly increase the number of ASP antimicrobial reviews
and interventions while maintaining a sustained impact on antimicrobial
utilization.
PMID- 29950189
TI - Wastewater drains: epidemiology and interventions in 23 carbapenem-resistant
organism outbreaks.
AB - For many years, patient-area wastewater drains (ie, sink and shower drains) have
been considered a potential source of bacterial pathogens that can be transmitted
to patients. Recently, evolving genomic epidemiology tools combined with new
insights into the ecology of wastewater drain (WWD) biofilm have provided new
perspectives on the clinical relevance and hospital-associated infection (HAI)
transmission risks related to these fixtures. To further clarify the clinical
relevance of WWD-associated pathogen transmission, reports of outbreaks
attributed to WWDs were selected for review that (1) investigated the outbreak
epidemiology of WWD-associated transmission of bacterial pathogens, (2) utilized
advanced microbiologic methods to establish clonality of outbreak pathogens
and/or resistance genes, or (3) described interventions implemented to mitigate
transmission of the outbreak pathogens from WWDs. These reports were collated,
compared, and analyzed, and the results are presented here.
PMID- 29950190
TI - Clinical course predicts long-term outcomes in bipolar disorder.
AB - BACKGROUND: The long-term outcomes of bipolar disorder range from lasting
remission to chronic course or frequent recurrences requiring admissions. The
distinction between bipolar I and II disorders has limited utility in outcome
prediction. It is unclear to what extent the clinical course of bipolar disorder
predicts long-term outcomes. METHODS: A representative sample of 191 individuals
diagnosed with bipolar I or II disorder was recruited and followed for up to 5
years using a life-chart method. We previously described the clinical course over
the first 18 months with dimensional course characteristics and latent classes.
Now we test if these course characteristics predict long-term outcomes, including
time ill (time with any mood symptoms) and hospital admissions over a second non
overlapping follow-up period in 111 individuals with available data from both 18
months and 5 years follow-ups. RESULTS: Dimensional course characteristics from
the first 18 months prospectively predicted outcomes over the following 3.5
years. The proportion of time depressed, the severity of depressive symptoms and
the proportion of time manic predicted more time ill. The proportion of time
manic, the severity of manic symptoms and depression-to-mania switching predicted
a greater likelihood of hospital admissions. All predictions remained significant
after controlling for age, sex and bipolar I v. II disorder. CONCLUSIONS:
Differential associations with long-term outcomes suggest that course
characteristics may facilitate care planning with greater predictive validity
than established types of bipolar disorders. A clinical course dominated by
depressive symptoms predicts a greater proportion of time ill. A clinical course
characterized by manic episodes predicts hospital admissions.
PMID- 29950191
TI - Five-year trends in adenoviral conjunctivitis in employees of one medical center.
AB - OBJECTIVE: To describe the 5-year findings after a policy to screen for,
diagnose, and isolate medical center employees with adenoviral conjunctivitis was
implemented. DESIGN: Observational report with a retrospective evaluation of a
current quality improvement initiative. SETTING: Johns Hopkins Medicine,
Baltimore, Maryland.ParticipantsJohns Hopkins Medicine employees. METHODS: Data
were retrieved from records maintained for this initiative, in which employees
with suspected adenoviral conjunctivitis were evaluated in the Occupational
Health Clinic and swabbed for polymerase chain reaction (PCR) testing for
adenoviral conjunctivitis. Signs, symptoms, work area, diagnoses, and disposition
of employees with eye complaints as well as PCR result and adenoviral type were
recorded. Five-year data were reviewed. RESULTS: From 2011 to 2016, of 10,000
full-time equivalent employees, 1,059 employees visited the Occupational Health
Clinic with suspicion of adenoviral conjunctivitis. Of these, 104 (10%) were PCR
positive for adenovirus. Of these PCR-positive employees, 26 (25%) had the worst
clinical presentation, epidemic keratoconjunctivitis (EKC). The Outpatient
Pharmacy had the highest number of adenoviral conjunctivitis cases (n=9). The
proportion of red-eye employees having PCR-positive adenoviral conjunctivitis
increased over 5 years (P<.005, Cochrane-Armitage test for trend) as did the
proportion of employees with EKC (P<.05). The proportion of employees with EKC
caused by type 37 also increased (P<.05). CONCLUSIONS: Adenoviral conjunctivitis
represents 10% of employee cases clinically suspected of this infection.
Employees in patient-care areas should be screened even if they have no direct
patient contact. Despite increases in the proportions of adenoviral
conjunctivitis and of EKC over 5 years, no outbreaks occurred. This policy helps
identify incipient EKC outbreaks and guides infection control efforts.
PMID- 29950192
TI - Near-patient environmental contamination of an intensive care unit with
Vancomycin-resistant Enterococci (VRE) and Extended-Spectrum Beta-Lactamase
Producing Enterobacteriaceae (ESBL-E) before and after the introduction of
chlorhexidine bathing for patients.
PMID- 29950193
TI - Effects of fulvic acids on goat sperm.
AB - SummaryThe effects of adding fulvic acids (FAs) to semen extenders on the quality
parameters of frozen-thawed goat buck spermatozoa remain undetermined. Buck semen
samples collected from six mature goat bucks once a week were diluted with Tris
egg yolk-based extenders. The diluted semen samples were supplemented with FAs
(0.2, 0.4 and 0.6%, w/w), cryopreserved, and evaluated for sperm-quality
parameters. Addition of FAs to the extender increased progressive motility,
acrosome integrity, membrane integrity, and superoxide dismutase and catalase
activities and decreased percentage abnormality and sperm malondialdehyde level
compared with the control group. However, excessive FA addition (>0.4%, w/w) to
semen extenders did not improve the efficiency. The results indicated that FAs
could be a promising cryoprotectant for goat buck sperm.
PMID- 29950194
TI - Role of plasma asymmetric dimethyl-L-arginine levels in detection of pulmonary
hypertension in children with CHD.
AB - OBJECTIVES: The objectives of this study were to evaluate the plasma levels of
asymmetric dimethyl-L-arginine in children with pulmonary hypertension due to CHD
before and after treatment with sildenafil and to evaluate its diagnostic and
prognostic value as a biomarker in such children. METHODS: A total of 60 children
with CHD and 30 healthy control children matched for age and sex were recruited.
Children with CHD were divided into two equal groups: the normal pulmonary
pressure group (n=30) and the pulmonary hypertension group (n=30). Children with
pulmonary hypertension were treated with sildenafil and were followed up for 6
months. Clinical data, haemodynamic parameters, echocardiographic examination,
and asymmetric dimethyl-L-arginine levels were evaluated before and after
treatment. RESULTS: Asymmetric dimethyl-L-arginine levels were significantly
higher in patients with pulmonary hypertension than in those with CHD-only or the
control group, and this increase was positively correlated with increased
severity of pulmonary hypertension. Asymmetric dimethyl-L-arginine levels, mean
pulmonary artery pressure, and pulmonary vascular resistance were significantly
decreased after treatment with sildenafil. Moreover, asymmetric dimethyl-L
arginine level was significantly lower in patients who responded to sildenafil
treatment compared with those who did not. At a cut-off point of more than 0.85
nmol/ml, asymmetric dimethyl-L-arginine has a sensitivity of 83% and a
specificity of 80% to diagnose pulmonary hypertension-CHD. Asymmetric dimethyl-L
arginine has a sensitivity of 100% and a specificity of 94% to predict poor
prognosis in pulmonary hypertension-CHD children at a cut-off point of 1.3
nmol/ml. CONCLUSION: Asymmetric dimethyl-L-arginine level has a good diagnostic
and prognostic value as a biomarker in children with pulmonary hypertension-CHD
and can be used for following up patients with pulmonary hypertension and
predicting response to treatment.
PMID- 29950195
TI - A multi-site exploration of barriers faced by vulnerable patient populations: a
qualitative analysis exploring the needs of patients for targeted interventions
in new models of care delivery.
AB - : AimTo investigate which populations of patients are considered 'vulnerable'
across varying clinical sites, and to identify the barriers encountered by these
patient populations limiting optimal health. BACKGROUND: Vulnerable patient
populations encounter diverse barriers that limit their ability to successfully
navigate the health system, potentially resulting in poor health outcomes. Little
current-day work has described types of barriers encountered by vulnerable
patient populations across numerous clinical sites and settings, which is
necessary to ensure health systems can begin to improve quality and disparities
for all patient populations. METHODS: An inductive content analysis was performed
based on field-site notes and digitally recorded telephone interviews with
providers/leadership at clinics/programs related to patient- and clinic-needs
from January 2014 through May 2015. Using thematic analysis with grounded theory
techniques, authors identified categories and themes. In total, 30 diverse
clinical sites/programs including inpatient- and outpatient-based clinics
providing medicine and surgery-based services were assessed through both site
visits and follow-up telephone interviews. Follow-up interviews were conducted
with one individual in various positions within sites/programs, including
physicians (n=15), registered nurses (n=8), clinic managers/coordinators (n=2),
clinical program coordinator (n=1), and care coordinator (n=1); one participant
represented three clinical sites.FindingsIn total, 30 sites/programs (n=30)
received both a site visit and follow-up interview. Commonly reported vulnerable
patient populations included those with multiple chronic conditions, lower
socioeconomic status, patients in a specific stage in the continuum of care, and
patients with over- and under-utilization of resources without a clear etiology.
Themes related to barriers included systems barriers (eg, insufficiencies of care
processes), clinic barriers (eg, lack of resources), patient-related barriers
(eg, housing, transportation), and provider-related barriers (eg, inadequate time
and knowledge). CONCLUSIONS: These results provide a framework to identify
systems- and clinic-related barriers that can be used in population health
management strategies aimed at improving health disparities within clinically
diverse sites.
PMID- 29950196
TI - [Hematopoietic Stem Cells or Hematopoietic Progenitor Cells Maintain the Steady
State Hematopoiesis? -Editorial].
AB - Current dogma suggests that hematopoietic stem cells (HSC) reside in the top of
the hematopoietic hierarchy, which can provide all kinds of mature blood cells
constantly through self-renewal and multilineage differentiation potential. HSC
has been regarded as the main cell population that maintains the stable
hematopoiesis and several differentiation and development patterns of HSC have
been summarized based on transplantation results. However, in deed the
transplantation experiment is based on an extremely situation of stress which
could not really reflect the function of HSC in normal homeostatic condition.
Recent studies show that hematopoietic progenitor cells (HPC) play the most
important role in hematopoiesis based on different experimental strategies. This
article focuses on the controversial subject of the function of HSC and HPC under
homostasis.
PMID- 29950197
TI - [HER2 Expression in Childhood ETV6/RUNX1+ Acute Lymphoblastic Leukemia and Its
Correlation with Clinical Features].
AB - OBJECTIVE: To explore the HER22 expression in children with ETV6/RUNX1 (E/R)
positive acute lymphoblastic leukemia(ALL) and to investigate the relationship
between the HER2 expression and clinical features. METHODS: Thirty-seven newly
diagnosed E/R-positive ALL children and 6 controls (4 cases of ITP and 2 healthy
children) were selected in Institute of hematology and blood disease hospital.
The 37 patients were divided into standard risk (SR), intermediate risk(IR), high
risk(HR) groups according to risk stratification; and they were divided into
relapse and non-relapse groups according to follow-up result. The CD10+CD19+
cells were sorted by flow cytometry. The mRNA was extracted from these cells.
Real-time fluorescent quantitative PCR was used to detect the expression level of
HER2. RESULTS: Among the 37 cases, 51.35% (n=19) were boys and 48.65% (n=18) were
girls and their median age was 4.72 (1.72-11.99) years old. Among the 6 controls,
50% (n=3) were boys and 50% (n=3) were girls and the median age was 5.24 (1.53
13.17) years old. The expression level of HER2 in E/R-positive ALL patients were
lower than that in controls (P<0.05). Although the difference of HER2 expression
level between the 2 groups failed to achieve statistical significance, the
expression level of HER2 in relapse patients were significantly lower than that
in non-relapse patients, and the HER2 expression in HR group patients were lower
than that in SR and IR groups. In addition, there was no significant correlation
between the expression level of HER2 and the sex, age, initial white blood cell
count, blast cell percentage and the level of LDH (P>0.05). CONCLUSION: The
expression level of HER2 in E/R+ ALL patients is lower than that in controls, and
in relapse group lower than that in non-relapse patient. Thus, HER2 may play
important roles in the pathogenesis and relapse mechanism of pediatric E/R
positive ALL patients.
PMID- 29950198
TI - [Experimental Research of Circular RNA hsa_circ_0000254 in Acute Myeloid
Leukemia].
AB - OBJECTIVE: To clone the circular RNA hsa_circ_0000254 and construct its
lentiviral over-expression vector. METHODS: The sequence of hsa_circ_0000254 (a
total of 524 bp long) was synthesized and cloned by using pGH vector. The vector
was cut by EcoR I and BamH I, and artificial hsa_circ_0000254 was obtained, then
inserted in pLCDH-ciR to construct the recombinant expression vector pLCDH
circ254(C254), which was confirmed by DNA sequencing. The lentiviral expression
vectors pLCDH-circ254(C254) and NC(pLCDH-ciR) were cotransfected into 293T cells
by lipofectamineTM 2000(lipo2000). After transfection for 40 hours, the cells
were collected and verified by PCR and sequencing. RESULTS: Restriction analysis
and DNA sequencing demonstrated that the lentiviral vector pLCDH-circ254(C254)
was constructed successfully, the expression efficiency increased 10000 times
after transfection of cells. CONCLUSION: The successful construction of the
lentiviral expression vector pLCDH-circ254(C254) results in the production of
high-titer lentivirus, so as to facilitate further study of the molecular
functions of hsa_circ_0000254.
PMID- 29950199
TI - [Expression and Clinical Significance of LncRNA KCNQ1OT1 in Patients with Acute
Myeloid Leukemia].
AB - OBJECTIVE: To investigate the expression of LncRNA KCNQ1OT1 in patients with
acute myeloid leukemia (AML) and to analyze the relation of LncRNA KCNQ1OT1
expression levels with clinicopathological features. METHODS: A total of 68
patients with AML were enrolled in the study, 48 out of them were suffered from
acute myeloid leukemia (AML) and 20 reached to complete remission (CR), 30 age
matched patients with iron-deficient anemia were included in control group, the
peripheral blood samples of all the patients were collected, and the real-time
fluorescent quantitative PCR (qRT-PCR) was used to detect the expression of
LncRNA KCNQ1OT1, meanwhile, the correlation of its expression with
clinicopathological characteristics and prognosis was analyzed. RESULTS: The
expression of LncRNA KCNQ1OT1 in AML patients was significantly higher than that
in the patient with complete remission and iron-deficient anemia (F=14.67,
P<0.01). The expression of LncRNA KCNQ1OT1 was not significantly different
between 20 cases of AML-CR and 30 cases of iron-deficient anemia (P>0.05). The
expression of LncRNA KCNQ1OT1 was associated with NCCN risk grade and survival
status in patients with AML. The median overall survival time was significantly
shorter in patients with high expression of LncRNA KCNQ1OT1 than that in patients
with low expression(P<0.05). CONCLUSION: LncRNA KCNQ1OT1 may be involved in the
regulation of AML. Expression of LncRNA KCNQ1OT1 and NCCN risk score can be used
as biomarkers of prognosis in the patients with AML and may be a potential
prognostic marker and therapeutic target for AML patients.
PMID- 29950200
TI - [Changes of Leukemia Stem Cells in Acute Myeloid Leukemia before and after
Treatment].
AB - OBJECTIVE: To investigate the presence of leukemia stem cells (LSC) in acute
myeloid leukemia (AML) and find out the relative position of leukemia cells in
the figures of flow cytometry, and to analyze the relationship between minimal
residual diseases (MRD) and the level of LSC, so as to explore the correlation of
LSC changes with the curative effect and the prognosis during chemical therapy.
METHODS: A total of 85 samples were collected from 50 AML (except M3) patients,
including 50 samples from the newly diagnosed patients, 7 samples of AML patients
with non-remission and 28 samples of AML patients with complete remission. All
samples were used for detection of LSC from immune phenotype of CD34+/CD38
/CD123+ by flow cytometry. The detection of immune phenotypic of leukemia cells
was performed in the newly diagnosed patients. The detection of leukemia-
associated immune phenotypes (LAIP) was implemented in the non-newly diagnosed
patients. RESULTS: The LSC was identified in the CD34+/ CD38-/ CD123+ in AML and
consistent with the relative position of the leukemia cell in flow cytometry
figures. Statistical analysis showed significant difference in LSC content
between the newly diagnosed AML group and the post-chemotherapy complete
remission group(P<0.01),but did not between the newly diagnosed AML group and the
post-chemotherapy non-remission group(P>0.05).There was significant positive
correlation between the LSC content and MRD level in 28 AML patients with
complete remission (r=0.680,P<0.01). CONCLUSION: LSC exist in AML and the
relative position are consistent with the leukemia cells in flow cytometry
figures, the size characteristics and weak expression of CD45 are also similar to
leukemia cells. The proportion of LSC decreases after chemotherapy. Detecting and
tracking the LSC changes in bone marrow and combination with detecting minimal
resident disease(MRD) may contribute to evaluate the theraputic efficacy and
prognosis of leukemia patients.
PMID- 29950201
TI - [Relationship between Early Peak Temperature and Neutropenia Duration in Acute
Leukemia Patients after Chemotherapy and Its Mechanism].
AB - OBJECTIVE: To investigate the relationship between early peak body temperature
and neutropenia duration and its potential mechanism. METHODS: A total of 111
patients with CR1 phase acute leukemia (AL) with neutropenia infection were
enrolled in this study. The relationship between early peak body temperature and
neutropenia duration was analyzed retrospectively, and the IL-6 serum level in
patients with different peak of body temperature was detected, and the single
cell culture system in vitro was established, the incorparation rate of EdU in
vivo was detected, and the effect of IL-6 on mouse hematopoietic stem cells
/progenitor cells was analyzed. RESULTS: Out of 111 patients with nentropenia,
the body temperature <38 degrees C and the neutropenia duration 9.5+/-3.69 d
were observed in 44 patients, while the body temperature >38 degrees C and
neutropenia duration 7.33+/-4.20 d were observed in 69 patients, the differences
between 2 groups was statistically signficant (P<0.05). The EdU test showed that
the number of EdU+ hematopoietic stem cells and progenitor cells increased. The
IL-6 level was different in patients with different peaks of initial bady
temperature (P<0.05). The results of amimal experiment showed that the IL-6 could
promote the proliferation of hematopoietic stem cells/ progenitor cells in vitro
and in vivo. CONCLUSION: For patients with neutropenic infection when initial
body temperature peak is <38 degrees C, the probability of neutropenia duration
prolonging after chamotherapy increases, which may relate with promotive effect
of pro-inflammatory cytokins on prliferation of hematopoietic stem
cells/progenitor cells.
PMID- 29950202
TI - [Values of Procalcitonin for Predicting Outcome of Infection in Acute Leukemia
Patients with Bacterial Bloodstream Infection].
AB - OBJECTIVE: To investigate the effects of serum procalcitonin(PCT) levels for
predicting the outcome of bacteria bloodstream infection in acute leukemia
patients. METHODS: Clinical data from 236 patients with acute leukemia
accompanied by bacterial bloodstream infection during July 2014 to November 2017
were retrospectively analyzed, 236 patients were divided into 5 groups (<0.05
ng/ml, 0.05- <0.5 ng/ml, 0.5- <2.0 ng/ml, 2.0- <10.0 ng/ml and >10.0 ng/ml)
according to PCT concentrations. RESULTS: The median age of patients was 40(13
73) years old. The male 123 cases(52.1%) and female 113 cases(47.9%) in 236
patients. The incidence of infection-related dealth in 5 groups was 0%, 1.4%,
13.8%, 25.0% and 33.3%, respectively; the incidence of septic shock and other
serious complications in 5 groups was 0%, 2.1%, 13.8%, 25.0%, 33.3% and 6.4%,
7.0%, 24.1%, 41.7%, 50.0%, respectively, showing the concentration dependent
manner and statistically significant difference (u=2127, P=0.000; u=2234,
P=0.000; u=4102, P=0.000). Further analysis showed that with the increase of PCT
concentration, the cumulative incidence of septic shock, infection-related death
and other serious complications was gradually increased with statistically
significance (HR=2.887, P=0.000, 95%CI:1.960-4.260; HR=3.158, P=0.000, 95%CI:
2.100-4.740; HR=2.158, P=0.000, 95%CI:1.550-3.000) respectively. Increased
procalcitonin level is an independent risk factor for septic shock and infection
related death (HR=2.517, P=0.000, 95%CI: 1.520-4.168; HR=2.881, P=0.000, 95%CI:
1.692-4.904)respectively. CONCLUSION: Serum procalcitonin level positively
correlates with the incidence of serious bacteria bloodstream infection
complications in the patients with acute leukemia. Increased procalcitonin level
is an independent risk factor for septic shock and infection-related death,
indicating that procalcitonin may be an important prognostic factor for infection
outcome in acute leukemia patients with bacteremia.
PMID- 29950203
TI - [Influence of FLT3-ITD Mutation and ITD Length on the Outcome on Patients with
Acute Myeloid Leukemia].
AB - OBJECTIVE: To explore the influence of FLT3-ITD mutation and ITD length on the
overall survival (OS) and relapse free survival(RFS) in patients with non-M3
acute myeloid leukemia. METHODS: Clinical features and therapeutic effect were
retrospectively analyzed in 75 AML patients with FLT3-ITD mutation and 76 FLT3
ITD- AML patients with a normal karotype from June 2011 to April 2016. Genomic
DNA was amplified by PCR, and FLT3-ITD mutation length was analyzed by DNA
sequencing in 40 patients. RESULTS: AML patients with FLT3-ITD mutation had
higher WBC count and the ratio of BM blast cells at initial diagnosis was also
higher than those in AML patients without FLT3-ITD mutation (95.13 vs
10.85)(P<0.01); 72% vs 59%(P<0.01). The CR rates in AML patients with FLT3-ITD
mutation less than those in AML patients without FLT3-ITD mutation(70.42% vs
94.7%)(P<0.01). OS (P<0.01) and RFS (P<0.01) were significantly increased in
patients with AML who received allo-HSCT as compared with the patients who
received consolidation chemotherapy and similar to AML patients without FLT3-ITD
mutation who received HSCT. Patients with maintenance sorafenib after HSCT had
longer OS (P<0.05) and RFS (P<0.05) than controls. ITDs exceeding 60 bp in length
were associated with decreasing OS as compared with shorter ITD in AML patients
with FLT3-ITD mutation (P<0.05). OS and RFS were similar among the 2 groups
receiving consolidation chemotherapy. Besides, the patients with allo-HSCT had
shorter ITDs and longer OS than ITDs exceeding 60 bp (P<0.05) and similar to AML
patients without FLT3-ITD mutation. CONCLUSION: AML patients with FLT3-ITD
mutation has poorer outcome, among which the prognosis was worse in patients with
ITD exceeding 60 bp, and the chemotherapy alone can not improve the prognosis of
FLT3-ITD+. Allo-HSCT is an effective treatment for AML patients with FLT3-ITD
mutation; Sorafenib appears to be an effective maintenance therapy after allo
HSCT in FLT3-ITD AML.
PMID- 29950204
TI - [Safety and Effectiveness of High Dose Tigecycline for Treating Patients with
Acute Leukemia after Ineffctiveness of Carbapenems Chemotherapy Combinating with
Febrile Neutropenia: Retrospective study].
AB - OBJECTIVE: To investigate the safety and efficacy of high dose tigecycline for
treatment of fibric neutrope-nia in acute leukemia patients after ineffectiveness
of carbapenems chemotherapy of acute leukemia. METHODS: The clinical data of 41
acute leukemia patients with febrile ncutropenia received high dose tigecycline
(100 mg q12h), who showed ineffectiveness of treatment with carbapenems, from
20151.30-2017.1. 29 in our hospital were collected and analyzed retrospectively.
The temperature, inflammatory indicators as well as hepatic and renal function
before and after treatment with tigecycline were compared. RESULTS: Among 41
patients treated with tigecycline due to ineffectiveness of treatment with
carbapenems, the infection had been controled in 34 cases, 7 patients died due to
ineffectiveness of anti-infective treatment, these patients all were patients
with relapse/refractory leukemia. 41 patients were examined etialogically, as a
result, 22 patients showed possitive, among them the gram-negative bacill was
found in 11(11/22) cases. The average deferves counce time of tigecycline was
28.2+/-12.0 hours. The temperature of patients treated with tigecycline for 48
hours decreased significantly (P<0.05). There were no significant differences in
calcitonin and C-reactive protein levels after treatment with tigecycline
(P>0.05), but cacitonin level displayed decrease tread. There was no hepatic and
renal impairment after treatment with tigecycline, but levels of as partate
aminotransferase, total bilirubin and blood area nitrogen in blood significantly
increased as compared with levels before treatment with tigecycline (P<0.05).
CONCLUSION: The application of high dose tigecycline for treatment of febrile
neutropenia is safety and effective. The high dose tigecycline can decrease the
temperature, calcitonin and C-reactive protein levels, and can control infection
without the hepatic and renal impairment, but it needs to be confimed by more
prospective studies.
PMID- 29950205
TI - [Effect of Steadily Down-regulating VE-Cadherin Expression on Susceptibitity of
K562 Cells to Chemotherapy].
AB - OBJECTIVE: To investigate the effect of steadily down-regulating the expression
of VE-cadherin on the chemotheraputic sensitivity of K562 cells, and explore its
possible mechanism. METHODS: Specifically targeting interference sequences
carrying human VE-cadherin were designed, the recombinant lentiviral vector
containing the IRES-GFP and NEO segment was constructed; recombinant lentivirus
was generated by three-plasmids packing system, and transfected into K562 cells,
then the cells steadily down-regulated were sorted. CCK-8 assay was performed to
evaluate the VE-cadherin of chemotherapeutic (Imatinib) sensitivity of K562
cells. The apoptosis was analyzed by flow cytometry with Annexin V/7-AAD double
labeling. The expressions of CD133 and ALDH1 mRNA were determined by real time
PCR. The protein expressions of VE-cadherin, BCR-ABL and beta-catenin were
analyzed by Western blot. RESULTS: The recombinant lentiviral vector pLB-shVEC
NEO-IRES-GFP was successfully constructed, packed into the lentivirus, then the
K562 cells steadily down-regulating VE-cadherin expression was obtained. When VE
cadherin was down-rengulated in K562 cells, the proliferation rate was reduced
while the the apoptosis rate was increased; the mRNA levels of CD133 and ALDH1
also were reduced; BCR-ABL fusion protein was not obviously changed; the total
beta-catenin protein, as well as the nuclear beta-catenin protein were decreased
in the K562/shVEC cells. Conclution: K562 cells are more susceptible to
chemotherapy when VE-cadherin is down-regulated, that may be realized via
reducing the stability and the nuclear transfer of beta-catenin protein.
PMID- 29950206
TI - [Establishment of Drug-resistant Acute Lymphoblastic Leukemic Cell Lines and
Their Resistance Mechanism].
AB - OBJECTIVE: To establish the adriamycin(ADR)-resistant ALL cell lines and to
investigate their drug-resistan mechanisms. METHODS: The drug-resistant cell
lines SUP-B15/ADR and RS4;11/ADR were derived by exposing the parental cells [SUP
B15(Ph+) and RS4;11(Ph-)] to the ascending concentrations of ADR. The cell
viability was detected by CCK-8 method. The expression of P-gp was examined by
Western blot, and RT-qPCR was performed to detect the expression of MDR1.
RESULTS: The drug-resistant cell lines SUP-B15/ADR and RS4;11/ADR were
successfully established, their resistance indexes were 14.088+/-0.763 and
10.473+/-1.024, respectively. After the cryopreserved SUP-B15/ADR and RS4;11/ADR
cells were resuscitated, their survival rates were 88.4+/-1.2% and 89.3+/-1.6%
respectively, while their resistance indexes were 13.976+/-0.967 and 10.342+/
0.846 respectively (P>0.05). When the drug-resistant cells were cultured in the
medium without ADR for 1 month, their drug-resistance indexes dropped down to
12.893+/-1.255 and 9.327+/-0.321 respectively(P<0.05). Drug-resistant cell lines
had the cross-resistance to cytarabine and etoposide. The expression of P-gp and
MDR1 in drug-resistant cells was significantly higher than that in wild-type
cells. CONCLUSION: Two drug-resistant ALL cell lines have been successfully
established by exposing to the ascending concentration of ADR. The over
expression of MDR1 and P-gp in drug-resistant cells may be one of the mechanisms
underlying the drug resistance.
PMID- 29950207
TI - [Relationship between the Therapeutic Dose of Arsenic Trioxide and Relapse in
Acute Promyelocytic Leukemia].
AB - OBJECTIVE: To analyze the correlation of ATO therapeutic dose with the relapse of
patients with acute promyelocytic leukemia (APL) and to investigate the optimal
dose and courses of ATO. METHODS: The clinical data of 102 patients with APL from
January 2008 to June 2015 were analyzed retrospectively. The clinical
characteristics of APL patients in relapsed group and maintained remission group
were compared. According to ATO dose in 2 years recommended in chinese guideline
as criteria of grouping, the patients were divided into ATO high and low dose
groups, then the relapse rate in groups was compared. The cut-off value of ATO
dose was analyzed by ROC curve. RESULTS: Univariate analysis showed that the
relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and
17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO
dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the
relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of
ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of
ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO
dose <8.765 mg/kg. CONCLUSION: The relapse of APL relates with used ATO dose,
sufficient use of ATO dose can decrease the relapse rate of APL.
PMID- 29950208
TI - [Effects of Arsenic Trioxide on Cdc20 and Mad2 in Acute Myeloid Leukemia HL-60
Cell Line].
AB - OBJECTIVE: To investigate the effects of arsenic trioxide (As2O3) on Cdc20 and
Mad2 in process of AML HL-60 cell proliferation. METHODS: The proliferation of HL
60 cells was detected by CCK-8 method at different concentrations of arsenic
trioxide for 24, 48 and 72 hours. The cell morphological changes were observed by
inverted microscopy. The expressions of Mad2 and Cdc20 mRNA and protein in HL-60
cells treated with As2O3 for 48 h were detected by real-time PCR and Western blot
respectively. RESULTS: Arsenic trioxide significantly inhibited the HL-60 cell
proliferation and displayed a good time-dose correlation. RT-PCR and Western blot
showed that the expression of Mad2 was up-regulated and the expression of Cdc20
was down-regulated in HL-60 cells treated with arsenic trioxide of different
concentration (4,8,10 umol/L). CONCLUSION: Arsenic trioxide can inhibit the human
acute myeloid leukemia HL-60 cell proliferation, and its mechanism may be related
with up-regulation of Mad2 expression and down-regulation of Cdc20 expression.
PMID- 29950209
TI - [Artesunate Suppresses Cell Proliferation of THP-1 Cells by Inducing Apoptosis].
AB - OBJECTIVE: To investigate whether Artesunate(ART) can inhibit the proliferation
of THP-1 cells and to explore the potential mechanism of its anti-leukemia
effect. METHODS: THP-1 cells were treated with 5 concentrations of Artesunate for
24 h, 48 h or 72 h. The viability of cells was detected with CCK-8 assay,
apoptosis was assessed by using flow cytometry, and the STAT3, Caspase3 and
Caspase8 protein levels were measured with Western blot . RESULTS: Compared with
the control group, ART significantly inhibited the proliferation of THP-1 cells
in a dose-dependent manner (r=0.9829, P<0.05). ART also increased the apoptosis
of THP-1 cells. The results of Western blot showed that after treated with ART,
the STAT3 protein expression in THP-1 cells was significantly down-regulated
(P<0.01), and the expressions of Caspase3, cleaved Caspase3 and Caspase8 proteins
were up-regulated(P<0.01). CONCLUSION: Artesunate can inhibit the proliferation
of THP-1 cells, which may relate with the down-regulation of STAT3 expression and
the activation of Capase3 and Caspase8.
PMID- 29950210
TI - [Relationship between PMP, FN, vWF and Bleeding Degree in Patients with Acute
Leukemia].
AB - OBJECTIVE: To detect the serum levels of platelet microparticle (PMP),
fibronectin (FN), and von Willebrand Factor (vWF) in acute leukemia (AL) patients
with thrombocytopenic and to analyze the relationship of the serum levels of PMP,
FN and vWF with bleeding degree. METHODS: One hundred and one newly diagnosed AL
patients from May 2014 to May 2017 were enrolled the AL group. According to the
WHO standard of bleeding stratification, 101 AL patients were divided into 5 sub
groups: 0, 1, 2, 3 and 4 score groups; 52 normal persons subjected to physical
examination were enrolled in control group. The PMP level was detected by flow
cytometry; the FN and vWF levels were detected by ELISA. The levels of PMP, FN
and vWF were compared between the AL group and the control group. The serum
levels of PMP, FN and vWF were compared according to bleeding degree group. The
relationship of bleeding degree with the serum levels of PMP, FN and vWF was
analyzed. RESULTS: The patients with newly diagnosed acute leukemia aged 18 to
60, and accounted for 61.39%. The degree of bleeding was mainly 1 score, which
accounted for 38.61%. The serum levels of PMP, vWF and FN AL groups were
significantly higher than those in control group (6.06%+/-4.38% vs 0.89%+/-0.50%,
205.82+/-24.89 vs 58.04+/-13.35 ug/L, 398.29+/-46.93 vs 311.37+/-26.02
ug/L)(P<0.001). The serum levels of PMP, FN and vWF were different among 5
subgroup (P<0.01); the level of PMP and FN were the highest in 0 score group and
the lowest in 4 score group; the vWF level was the highest in 4 score groups and
the lowest in 0 score group. The bleeding degree in the patients with acute
leukemia negatively correlated with PMP level, and positively with NF and vWF
levels (r=-0.753, r=0.648, r=0.805). CONCLUSION: According to the relationship of
the bleeding degree with serum levels of PMP, FN, vWF in patients, the detection
of PMP, vWF and FN levels can help to evaluale the bleeding degree in the
patients.
PMID- 29950211
TI - [Expression of CD19 and CD56 in AML Patients with RUNX1-RUNX1T1 Mutation and Its
Clinical Significance].
AB - OBJECTIVE: To investigate the clinical significance of RUNX1-RUNX1T1 expression
level in bone marrow of patients with acute non-M3 myeloid leukemia (AML non-M3),
and to understand the biological characteristics of RUNX1-RUNX1T1 positive AML
expressing lymphoid antigens CD19, CD56 and its effect on the initially induced
remission rate and prognosis. METHODS: The expression level of RUNX1-RUNX1T1 in
bone marrow of 200 patients with newly diagnosed AML (non-M3) was detected by
real-time fluorescent Q-PCR, the expression level of lymphoid antigens was
detected by flow cytometry, and the relationship of the initially induced
remission rate (CR1) with the overall survival (OS) rate was analyzed, the CR1
and OS differences also were analyzed between CD56+ and CD56- patients as well as
CD19+ and CD17- patients in RUNX1-RUNX1T1 positive patients with AML. RESULTS:
The CD56+ patients at the initial diagnosis had lower CR1(P<0.05) in RUNX1
RUNX1T1 positive AML patients, the CR1 of CD19+ patients was higher than that in
CD19- patients at the initial diagnosis (P<0.05). The OS of CD56+ patients was
significantly high in comparison with CD56- patients (P<0.05), while the OS
between CD19+ patients and CD19- patients was not significantly different.
CONCLUSION: The bone marrow CD56+ in RUNX1-RUNX1T1 positive AML patients suggests
poor prognosis. The CD19+ only correlates with CR1, but does not with OS.
PMID- 29950212
TI - [Relationship between Early Treatment Response and Prognosis in Children with
Acute Lymphoblastic Leukemia].
AB - OBJECTIVE: To analyze the relationship between the early treatment response and
the pregnosis in children with acute lymphoblastic leukemia(ALL). METHODS: Two
hundred and Seventy-eight ALL children diagnosed and treated in Hainan general
hospital from March 2013 to March 2017 were collected. All ALL children received
therapy with CCLg-ALL-2008 regimen. The 3 year event-free survival (EFS) rate of
ALL children in different groups was analyzed in terms of 4 indexes including
sensitivity response to prednison at day 8 (D8-SRP), bone marrow remission at day
15 (D15-BMR) and at day 33 (D33-BMR), and minimal residual disease at day 33 (D33
BMR), and minimal residual disease at day 33(D33-MRD). These 4 indexes and other
indexes possibly affecting the prognosis of ALL children were enrolled in Cox
regression model for analysis of independent factors affecting the prognosis of
ALL children. RESULTS: The D8-SRP test showed that among 269 ALL children,
240(89.22%) cases displayed prednisone poor response (PPR); the 3-year EFS rate
in predrisone good response(PGR) group was significantly higher than that in PPR
group(P<0.05). The D15-BMR detection showed that among 262 ALL children, the bone
marrow remission(BMR) as M1 was observed in 230 cases (87.79%), M2 in 20 cases
(7.63%) and M3 in 9 cases (4.58%); the 3-year EFS rate showed as follows:M1 group
>M2 group >M3 group(P<0.05). The D33-BMR detection showed that among 257 ALL
children, the BMR as M1 was observed in 227 cases (88.33%), M2 in 21 cses(8.17%)
and M3 in 9 caes (3.51%); the 3-year EFS rate in 3 groups showed as follows: M1
group >M2 group >M3 group(P<0.05). The D33-MRD detection showed that among 185
ALL children, MRD<10-10 was found in 128 cases (69.19%), MRD>=10-4-10-2 in 43
cases (23.24%), MRD >=10-2 in 14 cases (7.57%); the 3-year EFS rate in 3 groups
showed as follows: MRD <10-4 group > MRD>= 10-4-10-2 group>MRD>=10-2 group. The
Cox regression analysis showed that PPR in D8-SRP test, M2 and M3 in D15 and D33
BMR detection, and MRD>=10-2 in D33 MRD detection as well as T-ALL typing were
independent risk factors affecting the prognosis of ALL children. CONCLUSION: The
early treatment response can predict the prognosis of ALL children, which is an
independent prognostic factor for ALL children.
PMID- 29950213
TI - [Effects of Epihopin on Proliferation and Apoptosis of KG-1a cells and Its
Related Mechanism].
AB - OBJECTIVE: To explore the possible mechanism underlaying interference of epihopin
on the proliferation of AML KG-1a cells by inhibiting the Wnt/beta-catenin
signaling pathway, so as to prvide the experimental basis for development of drug
to treat the AML. METHODS: A total of 50 c57BL/6 mice were randomy divided into 5
group:blank control, model control, high, medium and low dose of epihopin. Except
the blank control group, the KG-1a cells were injected in abdominal cavity of 4
groups for the establishment of model. The mice in high, middle and low dose
groups were injected intramuscularly with 80, 40 and 20 mg/kg of epihopin
respectively, while the mice in blank control and model control group were
injected intramuscularly with saline. The Western blot was used to detect the
expression of S phase kinase-related protein 2(SKP-2), beta-catenin, E-cadherin
and poly-(ADP ribose) polymerase (PARP); the spectrophotometry was used to detect
the activity of caspase 3 and procaspase-3, the flow cytometry was used to detect
the cell cycle distribution and the apoptotic rate of KG-1a cells treated with
epihopin. RESULTS: The epihopin could enhance the activity of caspase 3, decrease
the level of procaspase 3; also could up-regulate the expression of E-acadherin
and down-regulate the expression of SKP-2 and beta-catenin; and could increase
the expression of PARP in dose-dependent manner. After KG-1a cels were treated
with epihopin, the apoptosis rate of cells significantly increased, the KG-1a
cells were arrested in G0/G1 phase, therefore the growth of KG-1a cells was
significantly inhibited. CONCLUSION: The epihopin can dose-dependently split PARP
to induce the apoptosis of KG-1a cells, its mechanism may relate with inhibition
of Wnt/beta-catenin signaling pathway and its down-stream-related gene
expression.
PMID- 29950214
TI - [Clinical Efficacy of Decitabine-Based Chemotherapy Regimens in the Treatment of
Newly Diagnosed Elderly Patients with Acute Myeloid Leukemia].
AB - OBJECTIVE: To investigate the safety and efficacy of decitabine combined with CAG
regimen in the treat-ment of newly diagnosed elderly patients with acute myeloid
leukemia(AML). METHODS: Fourty-nine patients with newly diagnosed acute myeloid
leukemia (except M3) who were admitted to our hospital were selected. All the
patients were older than 50 years old, and allogeneic hematopoietic stem cell
transplantation could not be performed for various reasons. Decitabine-based
chemotherapy regimens were used during induction therapy including single
decitabine therapy(DAC), decitabine combined with CAG regimen(DAC-CAG) and
decitabine combined with HAAG regimen(DAC-HAAG). Most of patients continued to
use the original treatment after complete remission, while others were given the
standard "3+7" regimen chemotherapy. A total of 2-4 courses of treatment was
conducted in the majority of patients. RESULTS: All of the 49 patients completed
the induction therapy, in which 26 cases achieved complete remission(CR), 7 cases
achieved partial remission(PR) and no response(NR) existed in 16 cases. The
complete remission and the overall response rate(ORR) were 53% and 67%
respectively. The overall response rate of DAC group, DAC-CAG group and DAC-HAAG
group were 17%, 77% and 63% respectively. 14 patients were infected and 1
patients died of pulmonary infection during the induction therapy. The median
number of suspended red blood cells and platelet infused were 9 units and 69
units respectively. Neutrophil recovery time was 15.1 days while the platelet
recovery time was 20.1 days during the induction therapy. The mean follow-up time
was 21 months. Overall survival(OS) was 75% at 6 months, 30% at 1 year, and 26%
at 2 year, while disease-free survival(DFS) was 83% at 3 months, 54% at 1 year,
and 47% at 2 year. The induction therapy could reach CR that was an independent
prognostic factor, however, the initial white blood cell count, platelet count,
age, chemotherapy regimen, prognostic stratification and whether complical by
pnenmonia during chemotherapy were not independent prognostic factors.
CONCLUSION: The induction efficacy of decitabine combined with chemotherapy is
superior to that of decitabine alone. The outcome of induction chemotherapy is an
independent prognostic factor, however, the high white blood cell count, poor
karyotype, complications and AML with myelodysplasia-related changes do not
affect long-term survival. DAC-CAG regimen is effective and have relatively few
adverse reactions in AML. It is suitable for the patients who are ineligible for
conventional chemotherapy.
PMID- 29950215
TI - [Downregulation of MCL-1 by Diallyl Disulfide Induces G2/M Arrest in Human
Leukemia K562 Cells and Its Mechanism].
AB - OBJECTIVE: To investigate the inducing effect of down-regulation of MCL-1 by
diallyl disulfide(DADS) on the G2/M arrest of human leukemia K562 cells and its
mechanisms. METHODS: CCK-8 was used to detect the effect of DADS on proliferation
of K562 cells, flow cytometry was employed to observe the effect of cycle arrest
by DADS and RNAi silencing MCL-1 gene in K562 cells. The expressions of MCL-1,
PCNA and CDK1 in K562 cells treated with DADS were detected by Western blot. The
amphigamy of MCL-1 with PCNA and CDK1 was detected by Coimmunoprecipitation.
RESULTS: CCK-8 detection showed that the inhibition rates of K562 cells treated
with 15, 30, 60, 120, 240 umol/L DADS were 32.48%, 59.34%, 66.42%, 77.06%, 81.05%
respectively (P<0.05). Flow cytometry analysis revealed that the perecentages of
G2/M cells were increased to 18.6% and 34.4%, 17.5% and 28.5%, respectively at 24
and 48 h after treating K562 cells with 60 and 120 umol/L DADS (P<0.05). And the
perecentage of G2/M cells of silencing MCL-1 was significantly increased
(P<0.05). Silencing effects of MCL-1+DADS on the cells were enhanced more
significantly as compared with DADS or MCL-1 alone (P<0.05). Western blot
exhibited that DADS could markedly downregulate the expression of MCL-1, PCNA and
CDK1(P<0.05). Coimmunoprecipitation revealed that MCL-1 bound with PCNA and CDK1,
then forming heterodimers, which were downregulated respectively more
significantly than that in the control group after treating K562 cells with DADS
for 8 h (P<0.05). CONCLUSION: DADS can inhibit the K562 cell proliferation and
induce them arrest G2/M through downregulation of MCL-1, then decreasing the
expression of PCNA and CDK1 in hunan leukemia K562 cells. Moreover, silencing MCL
1 can enhance the effect of DADS.
PMID- 29950216
TI - [Clinical Features, Treatment and Prognostic Factors of 94 Patients with
Follicular Lymphoma].
AB - OBJECTIVE: To investigate the clinical manifestation, therapeutic efficacy and
related prognostic factors of patients with follicular lymphoma. METHODS: A
retroretrospective study was conducted on 94 patients with follicular lymphoma
who were admitted to our hospital from March 1999 to June 2016. The total of 94
newly diagnosed FL patients were analyzed in terms of clinical manifestation,
laboratory data, pathological examination, clinical stage and so on, so as to
find out the related prognostic factors. RESULTS: Ninety-four patients were
included in this study. The median age at onset was 50.60 years old, more common
in women, and ratio of male to female was 1:1.35. The superficial lymphadenopathy
was found to be the first symptom in 72.3% patients, 25.5% patients had B
symptoms when diagnosed, 57.4% cases had extranodal organ invasion when
diagnosed, of which bone marrow invasion is the most common, accounting for
36.2%, followed by the digestive tract, bone, spleen and so on. The detected rate
of BCL-2 / IGH gene rearrangement was 33.9%. Patients with grade 3 of FL
accounted for 24.5%. Cases of clinical stage III-IV accounted for 71.2% in these
FL patients. The overall response rate (ORR) was 92.0%, and the complete
remission (CR) rate was 79.3% and the recurrence rate was 35.2%. The cumulative
overall survival rates of 3, 5 and 10 years were 92.1% , 84.6% and 77.4%
respectively, and the cumulative progression-free survival(PFS) rate in 3,5 and
10 years was 68.5%, 61.4% and 41.9%, respectively. The results showed that the CR
rate was 85.2% in patients treated with rituximab and 69.7% in patients treated
without rituximab. The OS and PFS in patients treated with rituximab were better
than those in patients treated without rituximab, but there was no significant
difference between them(P>0.05). Univariate analysis showed that FL stage, ECOG
score, Hb and LDH levels, digestive tract involvement or not, CR or not after
initial treatment had a significant impact on OS(P<0.05), while BCL-2, CD10, ECOG
score, albumin, Hb and LDH levels, percentage of lymphocytes, erythrocyte
sedimentation rate, digestive tract involvement had a significant impact on PFS
(P<0.05). Multivariate analysis showed that digestive tract involvement or not,
CR or not after initial treatment were independent risk factors for OS(P<0.05),
while CR or not after initial treatment, digestive tract invdvement or not, LDH
level and ECOG score were independent risk factors for PFS(P<0.05). CONCLUSION:
The FL is more common in middle-aged women, the FL was in late stage at confirmed
diagnosis, bone marrow involvement is more common. The CD10 negative is poor
prognostic factor for FL. The digestive tract involvement or not, CR or not after
initial treatment are independent risk factors for OS, while CR or not after
initial treatment, digestive tract involvement or not, LDH level and ECOG score
are independent risk factors for PFS.
PMID- 29950217
TI - [Incidence of Bone Marrow Involvement in Different Pathological Type Lymphoma
Patients].
AB - OBJECTIVE: To analyze the incidence of bone marrow involvement in patients with
different pathological types of lymphoma. METHODS: The results of bone marrow
tests including bone marrow aspiration(BMA), flow cytometry detection, bone
marrow biopsy(BMB) and 18F-FDG PET/CT, were analyzed retrospectively in 702 cases
of newly diagnosed lymphoma with bone marrow assessment in our hospital from
October 2000 to September 2016. If one of the above-mentioned 4 tests showed
positive, the lymphoma patient was judged as bone marrow involved. RESULTS: The
incidence of bone marrow involvement (BMI ) in the patients with NHL was much
higher than that in patients with HL [32.6 %(201/616) vs 15%(13/86)](P<0.05). For
patients with NHL, the incidence of bone marrow involvement in B-cell lymphoma
was higher than that in T-cell lymphoma (37.0% vs 22.6%)(P<0.05). According to
different pathological types, the incidences of BMI in the patient with mantle
cell lymphoma, hepatosplenic T-cell lymphoma, diffuse large B-cell lymphoma
(DLBCL) and follical lymphoma (FL) were 88% (25/22), 100% (5/5), 21.8% (56/257),
and 38.5% (15/39) , respectively. CONCLUSION: The incidence of bone marrow
involvement varies in different pathological types of lymphoma.Bone marrow
assessment has significant importance for stading of newly diagnosed lymphoma
patients.
PMID- 29950218
TI - [Effects of Silencing NSD2 Gene by shRNA on Proliferation, Apoptosis and Akt
/mTOR Signal Pathway in OCI-Ly3 Cells].
AB - OBJECTIVE: To investigate the effect of silencing NSD2 gene by RNA interference
on the proliferation, apoptosis and the alteration of Akt /mTOR signaling pathway
in diffuse large B cell lymphoma OCI-Ly3 cells. METHODS: The shRNA targeting NSD2
gene was transfected into OCI-Ly3 cells by lentivirus infection. The NSD2 mRNA
and protein were detected by real time Q-PCR and Western blot, respectively. The
cell proliferation was detected by CCK-8 and apoptosis was measured by flow
cytometry. The expressions of BCL-2, BAX, caspase-3, Akt, p-Akt, p-mTOR, p
P70S6K, H3K36me2 were detected by Western blot. RESULTS: After transfecting the
OCI-Ly3 cells by NSD2-shRNA for 72 h, the expressions of NSD2 mRNA and protein
both were down-regulated(P<0.05), the proliferation rate of cells in NSD2 shRNA
group was significantly lower than that in control and Neg shRNA groups (P<0.05);
the apoptosis rate of cells in NSD2 shRNA group was significantly higher than
that in control and neg-shRNA group (30.37+/-4.22)% vs 1.36+/-0.52 % and 2.17+/
1.43)%(P<0.05); the expressions of BAX and caspase-3 were up-regulated, while the
expression of BCL-2 was down-regulated; the H3K36me2 level significantly
decreased as compared with control group, no obvious decrease of the total
protein level of AKT was found, but the expressions of p-Akt, p-mTOR and p-70S6K
were down-regulated. CONCLUSION: The silencing NSD2 gene can inhibit the
proliferation and induce the apoptosis of OCI-Ly3 cells, their mechanisms may
relate with regulating the H3K36me2 level, specifically inhibiting the activivty
of AKT/mTOR signal pathway.
PMID- 29950219
TI - [Clinicopathological Features and Prognostic Factors of DLBCL].
AB - OBJECTIVE: To analyze the clinicopathological features and prognostic factors of
patients with diffuse large B-cell lymphoma(DLBCL). METHODS: Ninety-four cases of
DLBCL followed up were selected in Fujian Tumor Hospital. The
immunohistochemistry method was used to detect the protein expressions of BCL-2
BCL-6, MYC, CD10 and MUM-1, the gene abnormalities of MYC and BCL-2 were analyzed
by fluorescence in situ hybridization, and the clinical pathological features and
the related factors affecting prognosis in the patients with DLBCL were analyzed.
RESULTS: The protein positive rates of BCL-2, BCL-6, MYC, CD10 and MUM-1 in 94
patients were 75.53% (71/94), 58.51% (55/94), 52.13% (49/94), 15.96% (15/94) and
34.04% (32/94) respectively. The detection rate of MYC gene abnormality was
20.93% (9/43) and the detection rate of BCL-2 gene abnormality was 44% (22/50); 2
kinds of gene abnormalities were of multiple copies, and 2 cases (2.13%) were
abnormal in MYC and BCL-2 genes simultaneously. The median survival time of 3
years in 94 patients was 21.79 months (2-36 months), and the overall survival
rates of 1 and 3 years were 82.98% and 64.89% respectively. Single factor
analysis revealed that the high ECOG score (>= 2), high international prognostic
index (IPI) classification, positive expression of BCL-6 protein, and MYC and BCL
2 gene simultaneously abnormal were the risk factors influencing the prognosis
(all P<0.05). COX regression analysis showed that IPI classification, ECOG score
and treatment methods were independent factors influencing the prognosis (all
P<0.05). CONCLUSION: IPI classification, ECOG score and treatment methods have
greater impacts on the prognosis of patients with DLBCL. Chemotherapy combined
with radiotherapy or surgical treatment can significantly improve the prognosis
of patients.
PMID- 29950220
TI - [Analysis of Related Factors of Survival and Prognosis in Patients With High-risk
Refractory Lymphoma Treated with Auto-PBHSCT].
AB - OBJECTIVE: To analyze the factors affecting survival and prognosis of patients
with high-risk refractory lymphoma treated with autologous peripheral blood
hematopoietic stem cell transplantation (auto-PBHSCT). METHODS: A total of 96
cases of high-risk refractory lymphoma received auto-PBHSCT were selected. The
total survival rate after the treatment was analyzed by using Kaplan-Meier curve
and long rank test, and the prognosis-related factors were analyzed by univariate
analysis and COX regression analysis. RESULTS: The median survival time of 96
patients was 30.67 months, and the overall survival rate of 3 and 5 years after
treatment was 81.25% and 71.88% respectively. Univariate analysis showed that the
patients with high lactate dehydrogenase(LDH) level (>245 U/L), 3-5 scores of
international prognostic index(IPI), hepatitis B virus (HBV) infection, high
expression of Ki-67 (>=65%) and bone marrow infiltration had lower survival rate
(P<0.05). COX regression analysis showed that the complete remission wasn't
reached before auto-PBHSCT and the consolidation therapy was not carried out
after auto-PBHSCT, both of them were the risk factors affecting the prognosis
(OR=0.46, 0.12, 95% CI: 0.22-0.95, 0.02-0.82, P<0.05). CONCLUSION: Auto-PBHSCT in
the treatment of patients with high-risk refractory lymphoma can significantly
improve the survival status and prognosis, and the consolidotion therapy should
be performed after auto-PBHSCT so as to further improve the long-term survival
rate and prolong the survival time.
PMID- 29950221
TI - [Expression of Extracellular Matrix Protein Reelin in Patients with Multiple
Myeloma and Its Relationship with Prognosis].
AB - OBJECTIVE: To investigate the expression of extracellular matrix protein Reelin
(RELN) and its relationship with the prognosis of patients with multiple myeloma.
METHODS: The mononuclear cells were collected from bone marrows of multiple
myeloma patients by Ficoll gradient density centrifugation, the CD138+ cells were
then purified by flow cytometry, the mRNA level of RELN was detected by real time
PCR. The myeloma patients were divided into 2 groups according to the relative
expression levels of RELN. Then the relationship of RELN expression level with
clinical data was analyzed statistically. RESULTS: The high expression of RELN
significantly correlated with the percentage of CD138+ cells, progress-free and
total survival, but did not correlate significantly with DS (P>0.05) and ISS
stages (P>0.05). The RELN high expression group showed higher levels of serum M
protein, uric acid and serum calcium, lower hemoglobin, and more abnormal FISH
results (including RB1 deletion, 1q21 amplification, IgH recombination, P53
deletion, D13S319 deletion) than those in RELN low expression group. CONCLUSION:
Reelin correlates with the progression of multiple myeloma.
PMID- 29950222
TI - [Application of Chimeric Antigen Receptor-Modified NK Cells in Multiple Myeloma].
AB - OBJECTIVE: To explore the killing effect of CAR (CD138-CD28-CD3zeta)-NK cells on
myeloma cells through construction of CAR(CD138-CD28-CD3)-NK cells. METHODS: The
antiCD138scFv-CD28-CD3 zeta plasmid pcDNA3.1 was constructed, which then together
with 3 plasmid lentiviral packaging system were transfected into 293T cells, the
virus was collected. Furthermore, in order to get the stably transfected cell
line, the NK92MI cell line was infected by the virus, then the positive cells
were screened by puromycin. The expression of the CARNK cells were verified by RT
PCR and Western blot. At last the ability of secreting cytokine CD107a was
detected by flow cytometry, and the statistical analysis was carried out to
verify the anti-myeloma effect of CAR-NK cells. RESULTS: Gene fragment of the
CAR(antiCD138scFv-CD28-CD3zeta) was constructed successfully by gene engineering
technique in vitro, and the gene sequence was verified to be correct by
sequencing. By virus packaging technology, the virus expressing the protein of
the CAR was obtained. PCR and Western blot verified the expression of CAR fusion
protein on the sufurce of NK cells. The cell killing experiment confirmed that
the CAR-NK cells possessed the ability to secrete cytokine CD107a superior to
control cells and showed the obvious killing effect on multiple myeloma cells.
CONCLUSION: The CAR can be constructed in vitro, and express on NK92 cells. The
CAR-NK cells can kill the multiple myeloma cells expressing CD138 antigen,
thereby plays an antimyeloma effect.
PMID- 29950223
TI - [Diagnostic Value of IGF-I, beta2-MG and SF for Patients with Multiple Myeloma
and Their Relationship with Clinical Staging].
AB - OBJECTIVE: To investigate the diagnostic value of insulin like growth factor
I(IGF-I), beta2-microglobulin (beta2MG) and serum ferritin (SF) in patients with
multiple myeloma (MM) and their ralationship with clinical staging. METHODS:
Seventy-seven patients with MM treated in Depertment of Hematology of Shanghai
10th hospital and Oncology of Shanghai Armed Police Hospital from August 2016 to
June 2017 were enrolled in MM group, at same period 77 healthy volunteers were
enrolled in normal control group. The diagnostic value of IGF-I, beta2-MG and SF
for MM, and their levels in different stages of MM were compared. RESULTS: The
ROC analysis showed that beta2-MG and SF alone as well as their combination had
the diagnostic significance for MM, moreover the diagnostic value of IGF-I, beta2
MG and SF combination was highest, but the single IGF-I did not possess
diagnostic significance for MM. The comparison of IGF-I, beta2-MG and SF levels
in different stages of MM showed that the beta2-MG and SF levels in I stage were
higher than those in normal control group (P<0.05), but lower than those in II
and III stages (P<0.05). The IGF-I level in I stage was not statistically and
significantly different from IGF-I level in normal control group (P>0.05), but
lower than those in II and III stage (P<0.05). The relationship analysis between
IGF-I and beta2-MG, SF in different stages showed that the IGF-I related with SF
in I stage (r=0.417), but did not relate with beta2-MG; the IGF-I in II stage
related with beta2-MG and SF in II stage (r=0.543, r=0.426); IGF-I related with
beta2-MG and SF in III stage (r=0.425 and r=0.672). CONCLUSION: The diagnostic
value of IGF-I, beta2-MG and SF alone does not high for MM, but their combination
can significantly enhance the occurate rate of MM diagnosis. The levels of IGF-I,
beta2-MG and SF in II and III stages of MM all increase, moreover the level of
IGF-I correlates with the levels of beta2-MG and SF.
PMID- 29950224
TI - [Bone Marrow Morphology of Multiple Myeloma with Non-bone-related Extramedullary
Disease].
AB - OBJECTIVE: To explore the morphological characteristics of bone marrow cells of
multiple myeloma with non-bone-related extramedullary disease and thier clinical
significance. METHODS: Bone marrow smears, peripheral blood smears and bone
marrow biopsy sections as well as thier examination results of 20 cases of
multiple myloma with non-bone-related extramedullary disease were collected at
initial diagnosis in First Affiliated Hospital of Xi'an Jiaotong University from
March 2013 to March 2016, and morphological characterisistes of bone marrow cells
were analysed in combination with clinical data. RESULTS: The morphology of
plasma cells in 20 patients showed 2 cytologic subtypes: primitive cell type (16
cases) and pleomorphic type (4 cases). Immature plasma cells were found in the 5
patients' peripheral blood smear, accounting for about 1%-4% of the number of
peripheral blood cells. In bone marrow tissue, plasma cells hyperproliferated
with nodular and packed type, and secondary myelofibrosis counted for 12 cases
(60%). 13 MM patients whose non-bone-related extramedullary disease occurred
during therapy were divided into 2 groups according to the marrow fibrosis
density. The median time from diagnosis of MM to extramedullary lesions resulting
from fibrosis 0-1 grade and 2-3 grade was 23.7+/-3.7 months and 10.5+/-3.2 months
ahead of the former(P=0.025). CONCLUSION: Bone marrow plasma cell morphology of
multiple myeloma with non-bone-related extramedullary disease at the initial
diagnosis is mostly immature type, and plasma cells proliferate with nodular and
packed type and accompanied by different degree of fibrosis. The degree of
myelofibrosis indirectly reflects the degree of proliferation and malignancy of
the bone marrow plasma cells, which maybe possess some value in predicting
extramedullary disease in the early stages of the MM.
PMID- 29950225
TI - [Analysis of Success Rate and Influencing Factors for Collecting Peripheral Blood
Hematopoietic Stem Cells by Combination of CTX or E-CHOP Chemotherapy with
Mobilization of G-CSF in Patients with Multiple Myeloma].
AB - OBJECTIVE: To analyze the success rate and influencing factors for collecting
peripheral blood hematopoietic stem cells (HSC) by combination of
cyclophosphamide (CTX) or E-CHOP chemotherapy combined with granulocyte colony
stimulating factor (G-CSF) in patients with multiple myeloma. METHODS: The
clinical data of 75 patients with multiple myeloma in our hospital were
retrospectively analyzed. All patients received CTX or E-CHOP chemotherapy
combined with G-CSF mobilization to collect HSC, and the success rate (CD34+ cell
numbers was at least 2*106/kg) and its influencing factors were statistically
analyzed. RESULTS: A total of 86 collections by mobilization were performed in 75
patients, with the average 3.22 (0.12-22.28)*106/kg of CD34+ cells, and the
success rate of 74.42%. Single factor analysis revealed that the course number of
chemotherapy and disease status before the collection significantly correlated
with the success rate of HSC collection (P<0.05), and sex, age, disease type, ISS
stage and mobilization method showed no significant correlation with the
collection success rate (P>0.05). Multivariate Logistic regression analysis
showed that the course number of chemotherapy positively related with the success
rate of HSC collection (OR=2.95, 95% CI: 1.60-5.41, P<0.01), and there was no
significant correlation with the disease status before collection (OR=1.01, 95%
CI: 0.88-1.16, P=0.89). CONCLUSION: There are no significant effects of sex,
disease type, ISS staging and mobilization methods on the success rate of HSC
collection in patients with multiple myeloma, and the less course number of
chemotherapy (<5) before collection show a higher success rate of HSC collection.
PMID- 29950226
TI - [Effects of Autophagy Regulating Drugs on Proliferation, Apoptosis and Autophagy
of Multiple Myeloma Cells].
AB - OBJECTIVE: To investigate the effects of autophagy activator (rapamycin, RAPA)
and autophagy inhibitor (hydroxychloroquine, HCQ and 3-methyl adenine, 3-MA) on
the proliferation, apoptosis and autophagy of multiple myeloma cell line of
RPMI8226. METHODS: RPMI8226 cells were treated with autophagy regulating drugs of
different concentrations. The proliferation and apoptosis of cells were
determined by CCK-8 and flow cytometry, respectively. The expressions of
apoptosis-related proteins BCL-2, caspase-3 and PARP protein were assessed by
Western blot. Autophagy was detected by monodansylcadaverine staining. Autophagic
protein (LC-3b) and apoptosis-related proteins (caspase-3, PARP and BCL-2) were
analyzed by Western blot. RESULTS: RAPA and HCQ inhibited the proliferation of
RPMI8226 in a concentration- and time-dependent manner, and increased the
apoptosis. However, 3-MA did not show significantly inhibitory effect on the
proliferation and apoptosis of RPMI8226. MDC staining showed that the more
autophagic vacuoles could be detected in the higher concentration of RAPA, but
the less autophagic vacuoles in the higher concentration of HCQ and 3-MA. Western
blot showed that RAPA increased the expression of LC3-II/LC3-I, caspase-3 and
PARP, but inhibited the expression of BCL-2. HCQ inhibited the expression of LC3
II/LC3-I and BCL-2, but increased the expression of caspase-3 and PARP. 3-MA
inhibited the expression of LC3-II/LC3-I, but had no effect on the expression of
caspase-3, PARP or BCL-2. CONCLUSION: Rapamycin can inhibit the proliferation,
induce apoptosis and autophagy of RPMI 8226, the hydroxychloroquine can inhibit
autophagy and proliferation of RPMI 8226, and induce apoptosis, the 3-MA can
inhibit autophagy of RPMI 8226, but hardly has any effects on proliferation and
apoptosis of RPMI 8226 cells.
PMID- 29950227
TI - [Cost-Effectiveness Analysis of Different Chemotherapy Regimens in the Treatment
of Patients with Multiple Myeloma].
AB - OBJECTIVE: To compare the pharmaco-economic effect of 3 chemotherapeutic regimens
in the treatment of patients with multiple myeloma(MM). METHODS: One hundred and
thirty-eight newly diagnosed cases of MM in our hospital were analyzed
retrospectively, and then MM patients were divided into group A, B and C group
according to therapeutic regimen. Group A was treated with VCD therapeutic
regimen (bortezomib + cyclophosphamide + dexamethasone, 63 cases), The patients
in group B was treated with BiCTD therapeutic regimen
(clarithromycin+cyclophosphamide+thalidomide+dexamethasone, 44 cases), The
patients in group C was treated with CTD therapeutic regimen (cyclophosphamide+
thalidomide+dexamethasone, 33 cases). The clinical efficacy, adverse reaction,
cost-effectiveness were observed and analysed after 4 courses of treatment among
3 groups. RESULTS: The overall response rates of group A, B and C were 96.83%,
81.82% and 64.52% with statistical significant difference (P<0.01). The high
efficiency response rates of 3 groups were 82.5%, 59.09%, 32.26% with very
significant statistical difference (P<0.01). The infection rate of group A was
statistically and significantly higher than other 2 groups (P=0.048), and the
constipation rate in group A was statistically and significantly higer than that
in group B and C (P<0.05). The cost-effectiveness ratios of 3 groups were
69567.44, 20765.12 and 21475.48, respectively. The incremental cost-effectiveness
ratio of group A and B were 183933.21 and 22259.09, as compared with group C. The
result was in accordance with sensitivity test. CONCLUSION: Clinicial efficacy of
group A is the best,but group B has advantages on cost-effectiveness ratio as
compared with other groups, otherwise, group B has low incidence of adverse
reaction. In the view of safety, therapeutic efficacy and pharmacoeconomics for
treatment of patients with MM, the BiCTD regimen has been confirmed to be
superior to the other 2 groups.
PMID- 29950228
TI - [Mechanism and Clinical Significance of miR-373 In Elderly Patients with Multiple
Myeloma].
AB - OBJECTIVE: To study the mechanism and clinical value of miR-373 in multiple
myeloma. METHODS: The expressions of miR-373 in multiple myeloma cells and normal
plasma cells were detected by RT-PCR, and the biological function of miR-373 in
tumor was analyzed by MTT assay, flow cytometry, luciferase experiment and
tumorgenesis experiment. RESULTS: The miR-373 expression levels in MM patients
and multiple myeloma cell lines (H929, MM1S and U266) were significantly lower
than that in normal plasma cells detected by using RT-PCR (P<0.05). The
proliferations of U266 and H929 cells transfected with miR-373 were significantly
suppressed (P<0.05); the cell cycle of H929 cell transfected with miR-373 was
arrested in the G0/G1 phase(P<0.05) and the cell apoptosis was induced (P<0.05).
Luciferase experiment revealed that miR-373 could significantly inhibit the
expression of FOXM1 (P<0.05). In mouse tumorigenesis experiments, overexpression
of miR-373 significantly inhibited tumor growth by decreasing FOXM1 levels
(P<0.05). CONCLUSION: miR-373 inhibits tumor growth in MM by direct targeting
FOXM1, thus miR-373 shows an important clinical significance for the treatment of
MM.
PMID- 29950229
TI - [Clinical Efficacy and Safety of Different Doses of Dexamethasone Combined with
Bortezomib and Thalidomide for Treating Patients with Multiple Myeloma].
AB - OBJECTIVE: To study the clinical efficacy and safety of dexamethasone of
different doses combined with bortezomib and thalidomide for treatment of primary
multiple myeloma. METHODS: Ninety-six patients with multiple myeloma from January
2013 to January 2014 were randomly divided into group A (high-dose dexamethasone
+ bortezomib + thalidomide, 32 cases), group B (low-dose dexamethasone +
bortezomib + thalidomide, 32 cases) and group C (placebo + bortezomib +
thalidomide, 32 cases). The clinical efficacy and safety of patients was compared
among 3 groups. RESULTS: The overall remission rate (ORR) in group A and B was
significantly higher than that in group C (P<0.05), but the ORR was not
significant difference between group A and group B (P>0.05). After treatment, the
KPS and RNS score in 3 groups were significantly higher and lower than those
before treatment, respectively; the KPS score in group A and B was significantly
higher than that in group C (P<0.05), the RNS score in group A and B was
significantly lower C (P<0.05). After treatment, the positive expression rates of
CD38, CD56 and CD138 as well as small residual lesion (SRL) positive rate in 3
grops were significantly lower than those before treatment, but the positive
expression rate of CD19 was significantly higher that before treatment; the
positive expression rates of CD38, CD56 and CD138 as well as SRL positive rate in
group A and B were significantly lower thant those in group C, while the positive
expression rate of CD19 was significantly higher that in group C (P<0.05), but
the positive expression rates of CD19, CD38, CD56 and CD138 as well as SRL
positive rate were not significantly different between group A and B (P>0.05).
The incidence of fatigue, rash, peripheral neuropathy, anlmia, granulocyte
deficiance and so on in group B and C was significantly lower than that in group
A(P<0.05), but the difference in group B and C was not significant (P>0.05).
CONCLUSION: The therapeutic efficacy of different doses of dexamethasone combined
with bortezomib and thalidomide for patients with multiple myeloma is similar,
can obviously enhance remission rate, prolong the survival time, promote life
quality, but the incidence of adverse reactions in low dose dexamethason rigemen
is significantly reduced, and the safety is better.
PMID- 29950230
TI - [Clinical Analysis of Driver Mutations in Patients with Ph Negative
Myeloproliferative Neoplasms].
AB - OBJECTIVE: To explore the relationship between driver mutations and clinical
characteristics in patients with Philadelphia chromosome (Ph) negative
myeloproliferative neoplasms (MPN), so as to provide evidence for diagno-sis and
treatment of the disease. METHODS: The clinical data of 410 patients with classic
Ph negative MPN including 150 cases of polycythemia vera (PV), 188 cases of
essential thrombocythemia (ET) and 72 cases of primary myelofibrosis (PMF) from
January 2013 to December 2016 in Fujian Medical University Union Hospital were
retrospectively analyzed. The PCR or DNA sequencing were used for JAK2 V617F,
JAK2 exon12, CALR and MPL W515L/K mutation analyses, and follow-up information on
patients was updated by direct phone call or follow-up in outpatient. RESULTS:
Among the 410 patients with Ph negative MPN, 136 (33.2%) cases were asymptomatic
at diagnosis. 389 cases were sequenced and JAK2 V617F was detected in 87.1%
(122/140) of PV, 64.1% (118/184) of ET, 64.6% (42/65) of PMF; JAK2 exon 12
mutation in 1 case of PV; MPL W515L/K mutation in 1 case of ET and PMF,
respectively; CALR mutation in 18(9.8%) cases of ET and 5 (7.7%) cases of PMF.
JAK2 V617F mutated PV patients ocourred in older age: the white blood cell count,
platelet count and incidence of splenomegaly were higher than JAK2-negative PV
cases(P<0.05). Compared with JAK2 V617F mutated ET patients, CALR mutated ET
cases displayed younger age, lower leukocyte count, higher platelet count and
lower incidence of thrombosis; JAK2-negative ET cases had younger age, lower
leukocyte count, lower hemoglobin level, higher platelet count and lower
incidence of thrombosis(P<0.05). The incidence of splenomegaly in JAK2 V617F or
CALR mutated PMF patients was both higher than that in JAK2-negative PMF cases,
but the incidence of leukemia transformation in JAK2-negative PMF patients was
higher than that in JAK2 V617F mutated cases (P<0.05). CONCLUSION: The types of
driver mutations are closely related with the clinical features and prognosis in
Ph- negative MPN patients.
PMID- 29950231
TI - [Expression of Insulin-like Growth Factor Recepter Type I in CD34+ Cells of
Patients with Myelodysplastic Syndromes].
AB - OBJECTIVE: To explore the expression level of insulin-like growth facter (IGF-IR)
in CD34+ cells of patients with myelodysplastic syndromes(MDS). METHODS: Flow
cytometry was used to detect the expression of IGF-IR in the CD34+ cells of 100
MDS patients and 18 normal controls. RESULTS: The average IGF-IR expression level
in the CD34+ cells of 100 MDS patients (41.0+/-28.1)% was statistically and
significantly elevated in comparison with the corresponding level in normal
controls(4.3+/-1.8)%,(P<0.0001). The average expression level of 22 cases in high
risk groups was very significantly increased, compared with that in 78 cases of
low-risk groups[(66.5+/-27.8)% vs (34.5%+/-24.9)%](P<0.0001), and the average
expression level in 23 patients with chromosome abnormality was very
significantly increased in comparison with that in rest 77 patients [(56.0+/
30.9)% vs (36.9%+/-26.2)%](P<0.01). CONCLUSION: The over-expression of IGF-IR in
CD34+ cells of MDS patients suggests that the IGF-IR may involve in the origin,
occurrence and progress. The average IGF-IR expression level is markedly elevated
in high-risk groups and the patients who showed chromosome abnormality, this
trend revealed that IGF-IR correlates with malignant clonal proliferation in MDS
patients, thus providing a basis for their prognosis and outcome evaluation.
PMID- 29950232
TI - [As2O3 Up-Regulates the Proportion of CD4+CD25+CD127low Tregs in Peripheral Blood
of Patients with Severe Aplastic Anemia].
AB - OBJECTIVE: To investigate the effect of ATO on the proportion of Treg in the
peripheral blood of patients with severe aplastic anemia (SAA) in vitro. METHODS:
The peripheral blood of 20 newlydiagnosed patients were collected, and the
peripheral blood monomuclear cells (PBMNC) were extracted. After the PBMNC were
treated with ATO of different concentrotions (0, 1, 2.5 and 5 umol/L) for 96
hours, the proportion of CD44+ CD25+CD127low regulatatory T cells (Treg) were
detected by flow cytometry. The expression levels of Foxp3 mRNA were detected by
RT-PCR, and the levels of IFN-gamma,IL-4,IL-17 and TGF-beta1 were detected by
ELTSA to verify the results of flow cytomery. RESULTS: ATO significantly
increased the proportion of Treg (P<0.01) at the concentration of 2.5 and 5
umol/L, and the rising degree of Treg proportion improved with the increasing ATO
concentration(r= 0.524). Treg proportion increased at a concentration of 1
umol/L, but without statistical significance (P>0.05). At 1(P<0.05), 2.5(P<0.01)
and 5 umol/L(P<0.01), ATO significantly up-regulated the expression of Foxp3
mRNA, and the increase of Foxp3 mRNA positively and linearly correlated with the
increase of Treg cell-frequency(r=0.523). ATO significantly reduced the levels of
IFN-gamma (at ATO 1,2.5 and 5 umol/L, P<0.01), IL-4 (at ATO 2.5 umol/L, P<0.01;
at ATO 5 umol/L, P<0.01) and IL-17(at ATO 2.5 umol/L, P<0.05; at ATO 5 umol/L,
P<0.01). ATO had no significant effect on TGF-beta1 at 1(P>0.05) and 2.5 umol/L
(P>0.05), but significantly reduced TGF-beta1 level at 5 umol/L (P<0.05).
CONCLUSION: ATO can mediate the immune regulation through up-regulating the
proportion of Treg in peripheral blood of patients with SAA and reducing the
levels of IFN-gamma, IL-4 and IL-17.
PMID- 29950233
TI - [Changes of IL-21 and Its Mediated JAK/STAT Signaling Pathway in Patients with
Immune Thrombocytopenia].
AB - OBJECTIVE: To explore the correlation between JAK/STAT signaling pathways and
pathogenesis of immune thrombocytopenia(ITP). METHODS: Twenty-six newly-diagnosed
ITP patients was included in this study. They all meet the clinical and
hematological criteria for the diagnosis of ITP, and patients with coronary heart
disease, severe refractory hypertension, diabetes or with severe liver or kidney
function incompetence were ruled out. 24 healthy control without autoimmune
diseases, viral infectious diseases and with normal liver and kidney functions
were also included. The expressions of Jak3, p-Jak3 mRNA, Stat3, and p-Stat3 were
tested and the changes in levels of IL-21 mRNA, IL-21 cell secretion after DEX
intervention and AG490 blockade were measured. RESULTS: Compared with the healthy
control, patients with ITP had significantly high expressions of Jak3, p-Jak3
mRNA, Stat3 and p-Stat3 protein, which significantly reduced after AG490 blocking
(P<0.01). The expression of IL-21 mRNA and the secretion of IL-21 obviously
decreased after DEX intervention, but increased after AG490 blocking(P<0.01).
CONCLUSION: The pathogenesis of ITP associates with the activation of JAK/STAT
signaling pathways, and IL-21-mediated JAK/STAT signaling pathways play
regulatory role in ITP.
PMID- 29950234
TI - [Mutation Rate and Clinical Characteristics of CALR, JAK2 V617F and MPL W515K
Genes in Patients With Primary Thrombocythemia].
AB - OBJECTIVE: To analyze the mutation rate and clinical characteristics of CALR, MPL
W515K and JAK2 V617F genes in patients with primary thrombocythemia (PT).
METHODS: Fifty-six patients with PT were selected as the research objects in our
hospital. The CALR and MPL W515K gene mutations were determined by genomic DNA
PCR direct sequencing of the PCR products, and the JAK2 V617F gene mutation was
detected by allele specific PCR method. RESULTS: Among the 56 patients with PT
there were 14 cases of CALR gene mutation with the incidence rate of 25%,
including 6 cases of type I, 5 cases of type II and 3 cases of type III. The sex,
age, platelet(Plt) count, white blood cell (WBC) count and hemoglobin (Hb) level
in the type I case of CALR gene mutation all were not significantly different
from that in type II and III(all P>0.05); the WBC level in type III group
significantly increased in comparison of type II group (P<0.05), while the sex,
age, Hb and Plt levels showed no significant difference between the type III and
type II groups (P>0.05). There were 3 cases of MPL W515K gene mutation with the
incidence rate of 5.36%; 21 cases of JAK2 V617F gene mutation with the incidence
rate of 37.50%. There were 13 cases of CALR gene mutation in negative patients
with MPL W515K and JAK2 V617F (18 cases) with 72.22% incidence rate (13/18), and
there was no cases of 1 or 2 gene mutations coexisted. The levels of Hb and WBC
in peripheral blood of patients with CALR mutation were significantly lower than
those of JAK2 V617F mutation (both P<0.05). In 56 cases, there were 3 cases of
abnormal karyotype, with the incidence rate of 5.36%. The mutation rate of CALR
gene in abnormal karyotypes (66.67%) was significantly higher than that of normal
karyotypes (20.75%) (P<0.01). CONCLUSION: The incidence of JAK2 V617F gene
mutation increases in the patients with primary thrombocythemia; CALR mutation
rate is higher in the patients with negative MPL W515K and JAK2 V617F gene
mutation, which may closely correlate with abnormal karyotype; the levels of
peripheral Hb and WBC in PT the patients with CALR gene mutation are
significantly lower than those in patients with JAK2 V617F mutation.
PMID- 29950235
TI - [Effect of Blocking PYR Complex Binding to DNA Site by Peptide Nucleic Acid on
gamma-Globin Gene Expression].
AB - OBJECTIVE: To investigate the effect of blocking polypyrimidine complex binding
to DNA site by using peptide nucleic acid (PNA) on gamma-globin gene expression.
METHODS: PYR-PNA, beta-PNA and RS-PNA (random sequence-PNA) were designed and
synthesized, then were transfected into K562 cells with the cationic liposome
lipofectamine 2000 used as vector. The expression of gamma-globin gene at both
the transcriptional and translational level was detected by RT-PCR and the
Western blot respectively at 24 h, 48 h and 72 h after transfection with PNAs.
RESULTS: Compared with RS-PNA and control groups, the expression of gamma-globin
gene at mRNA and protein levels in PYR-PNA group was significantly up
regulated(P<0.05), especially at 48 h after tranfection, the levels of mRNA and
protein in PYR-PNA group were increased by 2.0 and 2.5 times than those in
control group, respectively. CONCLUSION: PYR-PNA can significantly up-regulate
the expression of gamma-globin gene in K562 cells, this study may provide a new
research idea for gene therapy of beta-thalassemia.
PMID- 29950236
TI - [Relationship between NLRP1 and Liver Dysfunction Following Allogeneic
Hematopoietic Stem Cell Transplantation].
AB - OBJECTIVE: To explore the effect of NLRP1 on the liver dysfunction following
allogeneic hematopoietic stem cell transplantation(allo-HSCT). METHODS: The mouse
model of allo-HSCT was established by using C57BL/6 and NLRP-/- mice were used as
the recipients: BABL/c mice were used as donors). The chimera rates of donor's
bone marrow cells were assayed by flow cytometry. ALT and AST levels were
measured by automatic biochemical analyzer. Western blot was used to detect the
expressions of NLRP1, the precursor of Caspase-1 and its active segment p20,IL
1beta,IL-18 and MPO in livers. RESULTS: The chimera rate was over 96% on the day
14 after allo-HSCT, and showed that the hematopoietic stem cells of donors had
been transplanted into recipients. ALT and AST levels were increased from
(173.9+/-12.39)U/L and (283.7+/-28.00)U/L on day 7 to (3902+/-1745)U/L and
(5316+/-924)U/L on the day 14 and decreased to (3153+/-564.4) U/L and (4350+/
957.7) U/L on the day 28, respectively. Western blot showed that the expression
of NLRP1 was increased after allo-HSCT, which displayed a similar trend with the
changes of ALT and AST. When knocking out NLRP1, the contents of ALT and AST in
the knocked group were significantly decreased in comparison with the group
without knocking out. And the expression levels of NLRP1 related inflammatory
proteins, precursor of Caspase-1,p20,Mature-IL-1beta,Mature-IL-18 and MPO were
lower than those in groups without knocking out NLRP1 gene. CONCLUSION: Allo-HSCT
can cause the damage of liver function and increase the expression of NLRP1,
while knocking out NLRP1 can reduce the damage of liver function, so NLRP1 may be
one of the important factors leading to liver dysfunction.
PMID- 29950237
TI - [Four Cases of Wernicke's Encephalopathy Following Hematopoietic Stem Cell
Transplantation].
AB - OBJECTIVE: To make through introduction of Wernicke's encephalopathy (WE)
following hematopoietic stem cell transplantation (HSCT) in terms of clinical
characteristics, diagnostic process and treatment. METHODS: The clinical
charactaristics, diagnostic and therapeutic process and prognostic follow-up in 4
patients diagnosed of WE following HSCT between January 2016 to January 2017 at
Department of Hematology, Chinese Aerospace Center Hospital were retrospectively
analyzed. RESULTS: Four patients included 2 ALL and 2 AML, and 3 males and 1
female, their age ranged from 8 to 20 years old. 4 patients accouted for about 3%
of all petients who received HSCT at that time. Typical triad syndrome consisting
of ocular motility disorders, ataxia, global confusion was seen in only 1
patient. However, confusion and heterophthongia as onset of this complication
were seen in all patients. Cerebral computed tomograph scan was universally
unremarkable and useless. Cerebral MRI scan disclosed that typical involvement
including thalamus, fourth ventricle, third ventricle, middle cerebral aqueduct
was seen in 3, while untypical site including mamillary body was in the remaining
1 patient. All received vitamin B1 supplement therapy by intramuscular injection
at a dose of 100 mg each day. Initial response was observed at 2, unknown, 3, 4
days after treatment and all obtained complete remission within 2 weeks without
any event of relapse after median follow-up period of 8 (7-12) months.
CONCLUSION: Any recipient of HSCT with clinical signs or symptoms of central
nervous system should receive vitamin B1 supplementary therapy immediately to
decrease risk of mortality of WE even if the diagnosis of WE is uncertain.
PMID- 29950238
TI - [Effect of Endomorphin-1 on Maturation and Expression of TLR4 in Peripheral Blood
Dendritic Cells Induced by High Glucose].
AB - OBJECTIVE: To investigate the effects of endomorphin-1 (EM-1) on the maturation
phenotype, cytokine secretion, T cell proliferation and TLR4 expression in human
peripheral blood dendritic cells (PBDCs) stimulated and induced by high glucose,
and to explore the regulatory mechanism of EM-1 on DC immune function. METHODS:
Peripheral blood mononuclear cells (PBMNCs) were induced into immature dendritic
cells (imDCs). The high glucose was used as the stimulating factor, and the EM-1
was used as the interventional factor. Then, the experiments were divided into
normal glucose group (NG group), high glucose group (HG group), high glucose plus
EM-1 group (EM group) and high glucose plus EM-1 and naloxone group (Nal group),
respectively. The PBDC's phenotype changes were detected by flow cytometry; ELISA
was used to detect the changes of cytokines secreted by PBDCs co-cultured with
autologous lymphocytes; CFSE was used to detect the proliferation of T
lymphocytes. TLR4 expression on PBDC surface was detected by RT-PCR. RESULTS:
Compared with HG group, the expression of PBDC surface molecules CD86, CCR7 and
CD36 was up-regulated in EM group (P<0.01), while the change of CD83 expression
was not statistically significant. However, IL-12 and IL-10 secreted by PBDCs and
the proliferation index of T-lymphocytes stimulated by PBDCs were both decreased
in EM group. Compared with EM group, the expression of CD86, CCR7 and CD36 was
decreased in Nal group (P<0.01), while the expression of CD83 was almost
unchanged (P>0.05). T-lymphocyte proliferation index was increased very
significantly in Nal group (P<0.01). The gray ratio of TLR4 in HG group was
higher than that in NG group, while the gray ratio in EM group's was very
significantly lower than that in HG group's (P<0.01). These results indicate that
the high glucose can promote the expression of PBDC TLR4, while the EM-1 inhibits
the expression of TLR4. CONCLUSION: EM-1 up-regulates the expression of PBDC
surface molecules CD86, CCR7 and CD36 stimulated and induced by high glucose, but
inhibites the induction of PBDC to maturity by high glucose. And the secreted
inflammatory cytokines IL-12 and IL-10 inhibites the proliferation of T
lymphocytes derived from PBDCs, while naloxone inhibites the effect of EM-1. EM-1
inhibites the expression of TLR4 on PBDC surface induced by high glucose.
PMID- 29950239
TI - [Efficiency of Inducing CIK from Cryopreserved PBMNC by Using Immune Cell SR].
AB - OBJECTIVE: To investigate the efficiency of inducing CIK from peripheral blood
mononuclear cells(PBMNC) by using immune cell serum replacement(immune cell SR),
so as to provide a new strategy for the industrialized production of immune
cells. METHODS: The PBMNC of healthy volunteers were collected, and these cells
were thawed after short-term cryopreservation and cultured to induce CIK cells.
The cells viability was measured by trypan blue exclusion, the phenotypes were
analyzed by flow cytometry, and the cytotoxicity was determined by Calcein-AM/PI
double staining. RESULTS: In cryopreserved PBMNC, the control group cells failed
to normally proliferate. Cell proliferation ratio was low in 2% SR group in
comparison with the fresh group, and the difference was significant (P<0.05),
however, differences were not statistically significant between 5% SR and fresh
group or between 10% AP and fresh group. CD3+, CD3+CD8+ and CD3+CD56+ cell
subsets were not significantly different before and after cryopreservation
(P>0.05). After being cultured, CD3+, CD3+CD4+, CD3+CD8+, CD3+CD56+ and CD3-CD56+
subsets and the cytotoxicity in vitro were not significantly different among all
group(P>0.05). CONCLUSION: 5% SR without the protein of animal origin can be
safely used as a substitute for autologous plasma in CIK induced from
cryopreserved PBMNC by culture, thus providing a basis for the application of
cryopreservation technique of immune cells to cell therapy.
PMID- 29950240
TI - [Efficacy and Safety of MSC Infusion in Treatment of Children with Refractory
LOHC: A Clinical Study].
AB - OBJECTIVE: To study the curative effect and safety of menchymal stem cell
infusion in treatment of children with refractory late-onset hemorrhagic
cystitis(LOHC) after allogeneic HSCT. METHODS: Thirty cases of children with
refractory LOHC after allo-HSCT in our department between December 2010 and July
2016 were analyzed retrospectively, out of 30 cases 7 received MSC treatment. The
used MSC of all were four-to-five generation MSC from bone marrows of third party
donors, and were infused into patients with (1.87+/-0.456)*106/kg MSCs once a
week (1-4 times in total) until the hematuria and odynuria symptoms being
improved. To observe whether unfavorable reactions occurred after MSC treatment,
the patients accepted daily physical examination and regular assistant
examination. The cytokine levels were also measured and dynamically detected in 2
cases before and after MSC treatment. RESULTS: In 30 children with refractory
LOHC, the hematuria difficultly reached the remission after routine hydration,
alkalizing and antiviral therapy, Among 25 cases who were received
methylprednisolone, MTX and CTX therapy, 7 cases received MSC infusion for 1-4
times with dose of (1.87+/-0.456)*106/(kg.time) as a result, 7 cases of LOHC were
cured. The TNF-alpha and IL-2R levels in 2 cases progressively decreased after
MSC infusion, no occurence of fever, rash, embolism and so on were found in 7
cases received MSC infusion; the BKV detection showed that the viral load did not
increase; the leukemia relapse or secondary cancer did not occure. CONCLUSION:
The MSC treatment is safe and effective for refractory LOHC after allo-HSCT.
PMID- 29950241
TI - [Evaluation of the Performance of Two Kinds of Anti-TP Enzyme-Linked
Immunosorbent Assay].
AB - OBJECTIVE: To evaluate the accuracy and precision of 2 kinds of anti-treponema
pallidum (anti-TP) ELISA reagents in our laboratory for detecting the anti-TP in
voluntary blood donors, so as to provide the data support for use of ELISA
reagents after introduction of chemiluminescene immunoassay (CLIA). METHODS: The
route detection of anti-TP was performed by using 2 kinds of ELISA reagents, then
546 responsive positive samples detected by anti-TP ELISA were collected, and the
infections status of samples confirmed by treponema pallidum particle
agglutination (TPPA) test was identified. The confirmed results of responsive
samples detected by 2 kinds of anti-TP ELISA reagents were compared, the accuracy
of 2 kinds of anti-TP ELISA reagents was analyzed by drawing ROC and comparing
area under curve (AUC), and precision of 2 kinds of anti-TP ELISA reagents was
compared by statistical analysis of quality control data from 7.1 2016 to 6.30
2017. RESULTS: There were no statistical difference in confirmed positive rate of
responsive samples and weak positive samples between 2 kinds of anti-TP ELISA
reagents. The responsive samples detected by 2 kinds of anti-TP ELISA reagents
accounted for 85.53%(467/546) of all responsive samples, the positive rate
confirmed by TPPA test was 82.87%. 44 responsive samples detected by anti-TP
ELISA reagent A and 35 responsive samples detected by anti-TP ELISA reagent B
were confirmed to be negative by TPPA test. Comparison of AUC showed that the
accuracy of 2 kinds of anti-TP ELISA reagents was more high, the difference
between 2 reagents was not statistically significant. The coefficient of
variation (CV) of anti-TP ELISA reagent A and B was 14.98% and 18.04%
respectively, which met the precision requirement of ELISA test. CONCLUSION: The
accuracy and precision of 2 kinds of anti-TP ELISA reagents used in our
laboratory are similar, and using any one of anti-TP ELISA reagents all can
satisfy the requirements of blood screening.
PMID- 29950242
TI - [Single Center Analysis of Pathogenic Characteristics of Lung Candida Infection
and Other Pathogenic Bacteria Infection in the Patients with Hemotological
Maliglancies in the Tropical Region of Hainan].
AB - OBJECTIVE: To analyze the infection characteristics of sputum and venous blood
pathogen in the patients with hematological malignancies and respiratory symptom
in the Hematology Department in tropical region and to investigate its drug
resistance so as to provide etiological evidence for clinical treatment. METHODS:
The pathogens and their drug-resistance of 2466 samples in the patients with
hematological malignancies and respiratory symptom in the Department were
analyzed retrospectively from January 2013 to November 2017. The samples were
collected from sputum and venous blood. RESULTS: The sputum sample culture in
patients with hematologic diseases showed that 224 strains were isolated, out of
them 98 strains (43.75%) were fungi mainly candida albicans (41 strains); and
then 88 Gram-negative strains (39.28%), among them the main pathogenic bacteria
were Escherichia coli(22 strains) and klebsiella Klebsiella pneumoniae(12
strains); and then 38 Gram-positive strains (16.96%), among them the main
pathogeni-bacteria were Enteroccocus (14 strains) and Gram-positive bacilli (14
strains). The blood samples culture of patients with hematologic diseases showed
that 61 strains were isolated, out of them the isolated rate of Gram-positive
bactetia was higherst, which accounted for 55.74%(34/61), mainly including
staphylococcus lominis (19 strains); and the isolated rate of Gram-negative
bacteria was 44.26% (27/61), among them main pathogenic bacteria was Klebsiella
pneumoniae (12 strains). The resistance test of pathogenic bacteria to drugs
showed that the resistant rate of Gram-negative bacteria to tigecycline, imipenem
and atl-962 duenner was lowest, while the Gram-positive pathogenic bacteria such
as Enterococcus, Gram-positive bacilli and Staphylococcus aureus were sensitive
to vancomycin, tigecycline and linezolid was high. CONCLUSION: the patients in
hematology department are infected easily in the hospital in tropical region. The
main pathogens are fungal strains in the respiratory tract of patients with
hematological malignancy according to the sputum culture results. The clinician
in tropical regions should choose suitable antibiotics for anti-infective
therapy, which is different from the situation in North China or other northern
areas.
PMID- 29950243
TI - [Research Progress on Metabolic Regulatory Mechanisms of Hematopoietic Stem Cells
-Review].
AB - Hematopoietic stem cells (HSC) are a class of stem cells with self-renewal and
multipotent differentiation into a variety of blood cells and are most thoroughly
studied, maturely applied in the clinic adult stem cell. Function of HSC is
closely associated with metabolic regulation. The metabolic state mainly
maintains HSC living in hypoxic bone marrow microenvironment depending on
glycolysis for energy metabolism, and keeping low reactive oxygen species (ROS)
level. Proteins like Hif-1, FoxO3, ATM, PTPMT1 protect HSC from ROS injury,
maintaining HSC in hypoxic state. In addition, glucose metabolism-related
enzymes, glutamine, fatty acid oxidation, purine and amino acid metabolism also
play important roles in metabolic regulation of HSC. In this review the research
progress on metabolism regnlation mechanisms of HSC is summurized, focusing on
the mechanisms releted with oxydation metabolism regulation, carbohydrate
metabolism level, purine metabolism and aminoacide metabolism.
PMID- 29950244
TI - [PD-1/PD-L1 Signaling Pathway and Its Anti-Tumor Effect in Lymphoma -Review].
AB - In tumor patients, programmed cell death-1 (PD-1) can inhibit T-cell activation
and proliferation by binding to its ligand, thereby promote tumor immune escape.
A large number of experiments showed that PD-L1 molecule highly expressed on
lymphoma cells, while PD-1 expression was up-regulated in tumor-infiltrating
lymphocytes, suggesting its role in the development of lymphoma, which may be an
important therapeutic target for lymphoma. PD-1 and PD-L1 monoclonal antibodies
can block the PD-1 / PD-Ls signaling pathway, restore T cell function, thus
inhibit the tumor growth. At present, a number of early clinical trials have
demonstrated the significant efficacy and less side effects in various subtypes
of recurrent lymphoma, which will be promising therapeutic agents. In this
review, the mechanism of PD-1/PD-L1 signal pathway, the expression of PD-1 / PD
L1 in lymphoma and the anti-tumor effect of its antibody in lymphoma are
summarized.
PMID- 29950245
TI - [Research Progress of Desialylation in Immune Thrombocytopenia -Review].
AB - Some patients diagnosed as immune thrombocytopenia(ITP) have poor response to
common first-line therapy such as corticosteroid and immunoglobulin. Studies in
recent years have found a FC-independent platelet clearance pathway exists, which
is characterized by desialylation of platelet surface glycoprotein(GP),
recognition and phagocytosis by Ashwell-Morell receptor(AMR) on hepatocytes,
independent on Fc receptors of the reticuloendothelial system. The up-regulation
of neuraminidase-1(Neu1) expression on platelet caused by various factors, such
as cold storage of platelet, septicemia and ITP could desialylate GPs. It has
been found that ITP with positive anti-GPIbalpha antibody mostly has a poor
response to first-line therapy and indicated that such antibody may lead to FC
independent platelet clearance. It also has been proved that anti-GPIbalpha
antibody could desialylate GPs on platelet in animal experiments. Researchers
have tris to use sialidase inhibitor agent to treat ITP and got a persistent
response of platelet. Here, the desialylation of platelet and its role in ITP
pathogensis and therapy are reviewed.
PMID- 29950246
TI - [Application Development of Blood Irradiation Indicator -Review].
AB - Transfusion-associated graft-versus-host disease (TA-GVHD) is known as one of
common complications of blood transfusion. The blood irradiation is generally
accepted as a proven method to prevent from this disease, for the reason that it
makes lymphocytes inactivated in blood products. The blood irradiation indicator
provides a guarantee of proper radiation dose, thus improving the transfusion
safety. Though widely used in developed countries for decades, the blood
irradiation indicator is still in the initial stage in our country. In this
review, the action principle, applications and applied value of the blood
irradiation indicator are summarized briefly.
PMID- 29950247
TI - [Research Progress on the Role of Pyroptosis in the Pathogenesis of
Myelodysplastic Syndrome -Review].
AB - Pyroptosis is a novel type of programmed cell death, which is closely related
with the pathogenesis of myelodysplastic syndromes (MDS). The recent studies
showed that all of S100A9/TLR4, S100A9/CD33 and Nox/ROS signaling pathways can
activate oxygen-sensitivity NLRP3 inflammasome and then induce the pyroptosis of
hematopoeitic stem cells (HSC) / hematopeitic pregenitor cells (HPC), resulting
in ineffective hematopoiesis in patients with MDS. Further studies on the role
and molecular mechanism of pyroptosis in the pathogenesis of MDS will provide the
potential opportunity for the diagnosis and treatment of MDS. Here, the recent
advances in the role and mechnism of pyroptosis in the pathogenesis of MDS are
reviewed.
PMID- 29950248
TI - [Senescent Mesenchymal Stem Cells Contribute to Progression of Myelodysplastic
Syndromes-Review].
AB - Myelodysplastic syndromes (MDS) comprise a group of malignant hematopoietic stem
cell (HSC) disorders characterized by ineffective hematopoiesis. The risk of
transformation to acute myeloid leukemia (AML) is increasing. The initiating
event in HSC of MDS leads to a growth advantage and subsequent clonal expansion,
that is still poorly understood. Accumulating data indicate that the mesenchymal
stem cells(MSCs) in MDS model display aberrant characteristics contributing to
disease initiation and transformation into AML. MSC derived from MDS displayed
the alteration in genetics, epigenetics and gene expression, which contribute to
altered morphology, impaired proliferative and differentiation capacity and
perturbed cytokine secretions, thus destroy in their ability to support normal
hematopoiesis and contribute to malignant progression. A number of promising
agents that target the interactions of the MDS clone with MSC are currently
investigated in various phases of clinical trial, that might ultimately result in
novel therapeutic strategies, targeting niche cells to attenuate leukemic
progression. In this article, the current status of MDS treatment, the
characteristics of MDS-MSC senescence and phenotypes, the changes of
hematopoietic function sapported by senescent MDS-MSC, the significane of MDS-MSC
in MDS prognosis and the MDS-MSC as potential target for treatment of MDS are
summarized.
PMID- 29950249
TI - Effects of Various Cleaning Agents on the Performance of Mice in Behavioral
Assays of Anxiety.
AB - Cleaning behavioral equipment between rodent subjects is important to prevent
disease transmission and reduce odor cues from previous subjects. However, the
reporting regarding the cleansing procedures used during such experiments is
sporadic and often incomplete. In addition, some investigators are reluctant to
clean devices between subjects because they are concerned that animals will react
negatively to the smell of the cleansing agents. We hypothesized that mice tested
on an elevated plus maze (EPM) soiled with excretions from conspecifics would
test as being more stressed than mice tested on the same apparatus that was
cleaned between animals. We tested the performance of C57BL/6J mice on an EPM
sanitized with 3 common cleaning agents-isopropyl alcohol, chlorine dioxide, and
bleach-and on an EPM soiled with rodent urine, feces, and presumably pheromones.
We further tested the potentially aversive nature of the cleansing agents by
using the classic light:dark box and a 2-choice light:dark box. Our data indicate
that cleaning the EPM compared with leaving it soiled did not affect performance
in male or female C57 mice, nor did cleaning agent choice. In addition, test
subjects did not react to the presence of the cleaning agents when incorporated
into the classic light:dark test. However, in the 2-choice light:dark test, mice
given the option to avoid an area containing a cleaning agent showed aversion to
all 3 agents, when all other conditions were equal. Given the lack of an
observable effect of cleaning on EPM performance, we recommend cleaning of the
EPM device between C57 mice to minimize the potential spread of disease.
PMID- 29950250
TI - Paediatric Spinal Cord Injuries in Pakistan.
PMID- 29950251
TI - Galactose-induced Aging Model in Rat Testicular Tissue.
AB - OBJECTIVE: To examine whether the D-galactose induced aging model is an
appropriate model for further aging research. STUDY DESIGN: Experimental study.
PLACE AND DURATION OF STUDY: Aziz Sancar Institute of Experimental Medicine,
Istanbul University, Turkey, June 2015- June 2017. METHODOLOGY: The study
comprises 3 groups of rats. Group I is young control (YC) 5-month-old rats. Group
II is 5-month- old rats, which were mimetically aged (MA) for 6 weeks via
intraperitoneal D-galactose (60 mg/kg body weight/day, 0.5 mL) administration.
Group III is naturally aged (NA) 24-month-old rats. Group I and III received
intraperitoneal saline (0.9% 0.5 mL) for 6 weeks as vehicle. Group I and Group II
received injections at 21 weeks age and Group III rats 6 weeks before 24 months
age. Tissues were harvested when rats became 6.5-month-old (Group I and Group II)
and 24-month-old (Group III). Quantitative biochemical analyses of proteins,
lipids, DNA biomarkers and Cu, Zn-SOD were conducted. Statistical analysis of the
data was conducted using ANOVA, followed by post-hoc Bonferroni test. RESULTS:
Higher magnitude of oxidative damage and diminished antioxidant defence capacity
were found in both mimetically aged and naturally aged testicular tissues. It is
observed that D-galactose aging model group shares significant similarities in
terms of impaired redox homeostasis with the naturally aged rats. CONCLUSION: D
galactose induced testicular aging model successfully mimics aging process.
Therefore, D-galactose induced aging model may be used as an accelerated aging
model to study the age related alterations and interventions.
PMID- 29950252
TI - Effectiveness of Oral Methotrexate Therapy versus Systemic Corticosteroid Therapy
in Treatment of Generalised Lichen Planus.
AB - OBJECTIVE: To compare the effectiveness of oral methotrexate versus systemic
corticosteroids in treatment of lichen planus. STUDY DESIGN: Randomised
controlled trial. PLACE AND DURATION OF STUDY: Department of Dermatology, Lady
Reading Hospital, Peshawar from September 2013 to February 2014. METHODOLOGY:
Patients with generalised lichen planus involving at least 20% of total body area
diagnosed clinically and were randomly allocated into two equal groups by lottery
method. Patients in group A were subjected to oral methotrexate 10 mg once weekly
for eight weeks with standard monitoring of full blood count and liver and renal
function tests. Patients in group B were subjected to oral corticosteroids 40 mg
for eight weeks taken daily than tapered according to the protocol. The results
were assessed at baseline and at the eighth week after starting the treatment.
The responses were analysed by Visual Analogue Scale (VAS) and sorted into four
categories: 0-3 = poor response, 4-5 = moderate, 6-7 = good, and >7 excellent
response. Chi-square test was applied to compare the efficacy in two groups with
significance of less than or equal to 0.05. RESULTS: Group A (methotrexate) had
47 (60%) male patients and 32 (40%) female patients. Group B (oral
corticosteroids) had 51 (64%) male patients and 28 (36%) females. Group A 55
(70%) patients had lichen planus in <50% of the body; whereas in group B 53 (67%)
patients had lichen planus in <50% of the body. Methotrexate was effective in 63
(80%) patients; whereas, oral corticosteroid was effective in 57 (72%) patients.
No remarkable side effects were observed with either agent. CONCLUSION:
Methotrexate is more efficacious than systemic corticosteroids, but the effect is
not statistically significant.
PMID- 29950253
TI - Relationship of Nutritional Status and Functional Capacity in Elderly Patients
Visiting Outpatient Clinics of a Tertiary Care Hospital.
AB - OBJECTIVE: To determine the correlation of functional and nutritional status of
elderly patients (equal to and more than 60 years of age) visiting family
medicine clinics of tertiary care hospital in Karachi. STUDY DESIGN: Cross
sectional, descriptive study. PLACE AND DURATION OF STUDY: Family medicine
clinics of Aga Khan University Hospital, in Karachi, from August 2014 to February
2015. METHODOLOGY: A total of 200 participants (60 years and above), Family
medicine outpatient clinics, were recruited via non-probability consecutive
sampling. Katz scoring and MNA scale were used for the evaluation of functional
and nutritional status, respectively. Spearman's rank correlation coefficient was
applied to assess the correlation between nutritional status and functional
status of elderly. RESULTS: Out of 200 participants, 35 % (n=70) were of 60-64
years of age. Most of them (54%, n=109) were males as compared to 46% (n=91)
females; 33.5% were at risk of malnutrition and 35.5% were dependent. Spearmen
correlation between functional and nutritional status was rho = -0.675, with p
value of p<0.001. CONCLUSION: There is a negative correlation between nutritional
and functional status. As good nutritional status is essential for older persons
to become functionally active; hence, this issue needs to be dealt in a
developing country like Pakistan.
PMID- 29950254
TI - Outcome of Endoscopic Management of Post Living Donor Liver Transplant
Anastomotic Strictures.
AB - OBJECTIVE: To evaluate the therapeutic efficacy of endoscopic dilatation of
anastomotic stricture (AS). STUDY DESIGN: An observational study. PLACE AND
DURATION OF STUDY: Department of Gastroenterology and Hepatology, Shaikh Zayed
Hospital, Lahore, Pakistan from November 2016 to November 2017. METHODOLOGY:
Patients presenting with anastomotic biliary stricture following living donor
liver transplant (LDLT) underwent endoscopic retrograde cholangio
pancreaticography (ERCP) and treatment of their strictures with dilatation with
or without stenting. The patients were then followed up to see adequate
resolution of stricture and repeat therapeutic ERCP was performed, if required.
The patients were labelled as cured if stricture resolution persisted for a
period of up to six months following ERCP. RESULTS: Forty-three patients (32
males and 11 females), with post-LDLT AS, who met the inclusion and exclusion
criteria were enrolled in the study. Thirty-six (83.7%) patients had a single
biliary anastomosis while seven (16.3%) patients had two anastomoses. Ductoplasty
was done in 15 (34.9%) of the enrolled patients. Patients with post-LDLT AS
required 3.65 +1.15 sessions of ERCP. Plastic type biliary stent was used in
seven (16.3%) patients, balloon dilatation alone was done in five (11.6%)
patients and combined balloon dilatation and stent placement was performed in 29
(67.4%) patients, and combined graduated dilator and stent placement was
performed in two (4.7%) patients. Five (11.6%) patients required rendezvous
procedure (whereby a radiologist placed a guidewire percutaneously into the
biliary system) as guidewire placement across stricture site was endoscopically
unsuccessful. The overall success rate was 88.4%. Mean stent free follow-up was
7.18 +1.38 months. Recurrence of AS was noted in one (2.3%) patient. CONCLUSION:
Endoscopic management of post-LDLT AS has an efficacious long-term outcome.
PMID- 29950255
TI - Immune System Activation in Rheumatic Heart Disease.
AB - OBJECTIVE: To assess activation of immune system in rheumatic heart disease (RHD)
patients in the form of AECA, ACL and anti GBM antibodies. STUDY DESIGN:
Descriptive, observational study. PLACE AND DURATION OF STUDY: Department of
Immunology, University of Health Sciences (UHS), Lahore, and Outpatient
Department, Punjab Institute of Cardiology, from February 2015 to January 2016.
METHODOLOGY: Clinically suspected patients of RHD and confirmed by
echocardiography were included. AECA, ACL and anti GBM antibodies were
investigated in the sera of RHD patients. RESULTS: Eighty-six RHD patients were
included in the study; the mean age of the patients was 30 +/-9.3 years. Among
these patients, 59 (68.6%) were females and 27 (31.4%) were males. AECA was most
commonly detected autoantibody i.e. in 17 (19.8%) patients; whereas, ACL was
detected in only 2 (2.3%) subjects. Another 2 (2.3%) patients had both AECA and
ACL antibodies. AGBM was not detected in any of the patients. ACL was seen in
females with isolated MR. AECA were seen in mixed valvular heart disease
patients. CONCLUSION: Immune system gets activated in RHD patients leading to
formation of different antibodies, and they are also related to the type of
lesion. ACL antibodies are present in females with isolated mitral regurgitation,
while AECA are present in both the genders with mixed valvular heart disease.
Anti GBM antibodies are not seen in RHD patients.
PMID- 29950256
TI - Gene Expression of Glyoxalase II in Diabetic Retinopathy.
AB - OBJECTIVE: To study the gene expression of Glyoxalase II among patients of
diabetic retinopathy. STUDY DESIGN: A cross-sectional comparative study. PLACE
AND DURATION OF STUDY: CREAM (Centre for Research in Experimental and Applied
Medicine) and the Department of Biochemistry and Molecular Biology, Army Medical
College, Rawalpindi in collaboration with Armed Forces Institute of Ophthalmology
(AFIO), Rawalpindi, from November 2015 to November 2016. METHODOLOGY: Individuals
were enrolled, among whom 30 were cases with diabetic retinopathy and 30 were
controls without the disease. Their relevant data were collected and blood
samples were drawn. Individual RNA was extracted from respective samples and cDNA
was synthesised from each. Expression analysis for Glyoxalase II was done and
relative quantification was done using delta delta CT method. RESULTS: A total of
60 individuals of ages 40-70 years were enrolled in the study, 30 cases and 30
controls. Among these, 34 (56.67%) were males and 26 (43.3%) were females. Mean
ages were 60 +/-8 years in cases and 59 +/-13 years in controls. Down regulation
of Glyoxalase II was observed in cases as compared to controls. CONCLUSION:
Downregulation of Glyoxalase II, seen among patients of diabetic retinopathy, may
indicate a failure of detoxifying system leading to accumulation of glycated end
products.
PMID- 29950257
TI - Expression of Epidermal Growth Factor Receptor in Colorectal Adenocarcinoma and
its Correlation with Clinicopathological Factors.
AB - OBJECTIVE: To identify the expression of epidermal growth factor receptor (EGFR)
in colorectal cancer (CRC) and its relationship with clinicopathologic factors.
STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of
Laboratory and Blood Bank, King Abdul Aziz Specialist Hospital, Taif, Saudia
Arabia, from January 2008 to June 2011. METHODOLOGY: Diagnosed cases of
colorectal carcinoma reports and slides were reviewed and cilnicopathological
features were recorded. EGFR immunohistochemical staining was performed. All
slides were assessed by light microscopy and scored after assessing the
percentage of cells staining (grade) and intensity of the staining. Colectomy
specimens of colorectal carcinomas with complete clinical information and good
fixation were included. Biopsies specimens diagnosed as colorectal
adenocarcinomas were excluded. The studied characteristics included age, gender,
clinical presentation, tumor site, tumor size, degree of histological
differentiation (well, moderate, poor), vascular and perineural invasion.
Statistical analysis was done by SPSS version14 and Chi-square test was used for
comparing the histological factors with EGFR expression. RESULTS: Thirty-five
colectomy specimens showed mean age of 61.5 +/-12.36 years and male to female
ratio 1:2 (35% and 65%, respectively). Expression of EGFR was detected in 74% of
the studied specimens. There was strong expression in most of cases. EGFR
expression was found in mostly grade II (85%) and stage T3 tumors (69%).
CONCLUSION: Patients presented mostly with late stages of CRC and EGFR was
expressed on tumor cells in the majority.
PMID- 29950258
TI - Epidemiology, Clinical Features and Consequences of Spinal Cord Injury in
Children.
AB - OBJECTIVE: To describe epidemiology, clinical features and clinical consequences
of Spinal Cord Injury (SCI) in children. STUDY DESIGN: Case series. PLACE AND
DURATION OF STUDY: Paraplegic Centre, Hayatabad, Peshawar, from July 2011 to
March 2017. METHODOLOGY: SCI patients having age up to 15 years, admitted to
Paraplegic Centre, were inducted in 2017. Exclusion criteria was foreign-national
SCI patients, and/or SCI patients re-admitted to paraplegic centre. List of all
SCI patients admitted to the centre was retrieved and 102 patients were
identified. Data of these patients was evaluated for demographic information,
physiological intactness (complete SCI/incomplete SCI), neurological level and
complications. RESULTS: A total of 102 patients (66 males and 36 females) with
mean age 10.9 +/-3.7 years were included in this study. Firearm injury was the
most common cause (n=39, 38.2%) of SCI in these patients, followed by fall from
height (n=23, 22.5%), road traffic accidents (n=14, 13.7%), and weight fallen
over (n=14, 13.7%). Bomb blast injury (n=7, 6.9%), diving accident (n=3, 2.9%),
and sports related injuries (n=2, 2.0%). Majority of the patients (n=82, 80.4%)
had complete SCI (ASIA A); the commonest SCI level was thoracic region (n=59,
57.8%) and the least reported region was (n=14, 13.7%) cervical. Out of the
total, 50 (49.0%) patients had pressure ulcer in which 15 (30.0%) patients were
having grade IV pressure ulcer, 9 (18.0%), 15 (30.0%) and 11 (22.0%) patients
were had grade I, grade II and grade III pressure ulcer, respectively.
CONCLUSION: Majority of causes of SCI in children are similar to those reported
in adult population. However, the commonest causes of SCI in children in Pakistan
were firearm injury and bomb blast, which are rarely reported in other countries.
Like adult population, these children with SCI are prone to developing pressure
ulcer.
PMID- 29950259
TI - Assessment of Frequency and Transience Rate for Ventilator-Associated Pneumonia
(VAP) in Geriatric Patients in Tertiary Care Settings of Karachi, Pakistan.
AB - OBJECTIVE: To assess the risk factors, frequency and transience rate for
ventilator-associated pneumonia in geriatric patients. STUDY DESIGN: Cross
sectional, descriptive study. PLACE AND DURATION OF STUDY: Various campuses of
Ziauddin University Hospital and Civil Hospital, Karachi, from April 2016 to May
2017. METHODOLOGY: Critically ill geriatric patients (aged 60 years and above) in
intensive care units, were selected who had received mechanical ventilation.
Various risk factors, microbial fate, and related clinical outcomes were measured
in the selected cohort of 350 patients. RESULTS: It was found that 72% (n=252) of
study population was elderly who received ventilation for more than 48 hours with
a higher mortality rate of 59.5%. Frequency of VAP was found to be 18% (n=63). A
high rate of VAP was observed in geriatric cohort, i.e. n=47 association of age
in VAP (p=0.611) in non-significant while mortality values and admission status
were significantly associated with VAP (p<0.001). CONCLUSION: The factual
challenge nowadays is to present the real estimate of the clinical consequences
of VAP in geriatric cohort. Such studies will help in formulating an optimal
institutional policy and rational approach to decrease rates of mortality.
PMID- 29950260
TI - Influence of Obesity on Gleason Score Inconsistencies between Biopsy and Radical
Prostatectomy Specimens.
AB - OBJECTIVE: To evaluate the association of obesity with Gleason scores determined
in biopsy and radical prostatectomy specimens. STUDY DESIGN: Cohort study. PLACE
AND DURATION OF STUDY: Urology Department, Fatih Sultan Mehmet Research Hospital,
Istanbul, Turkey from 2007 to 2015. METHODOLOGY: A total of 111 patients, younger
than 65 years who underwent radical prostatectomy (RP) with the diagnosis of
prostate cancer, were included in the study. Histopathology reports of the
surgical, and TRUS-guided prostate biopsy specimens were analysed. Body mass
index (BMI) and prostate specific antigen (PSA) levels were also evaluated.
RESULTS: Mean age of the patients was 59.06 +/-4.10 (range = 47-64 years) years.
Mean BMI of the patients was 25.59 +/-3.24 kg/m2 (range = 19-35 kg/m2). In
patients whose BMI measurements were equal or above 25 kg/m2; a significant
difference was found between Gleason scores of the needle biopsy and RP specimens
(p=0.001). CONCLUSION: BMI and PSA, which are known to be the most important
parameters effecting Gleason score, were evaluated in combination. Regarding non
concordance with Gleason scores, it has been observed that as a predisposing
factor, obesity can explain these incompatibilities similarly to PSA.
PMID- 29950261
TI - Diagnostic Accuracy of InitiaI Chest X-Rays in Thorax Trauma.
AB - OBJECTIVE: To evaluate the efficacy, sensitivity and specificity of chest x-ray
as a diagnostic imaging tool in management of thorax traumas. STUDY DESIGN:
Descriptive study. PLACE AND DURATION OF STUDY: Haydarpasa Numune Training and
Research Hospital, Istanbul, Turkey, between December 2014 and December 2015.
METHODOLOGY: Case records of patients admitted to the emergency department with
thoracic trauma were retrospectively analysed through the hospital database.
Plain postero-anterior chest X-rays and thorax computerised tomography (CT) scans
were evaluated seperately by same radiologist. Accurcy of signs of thoracic trama
was determined using CT scan as gold standard. RESULTS: Nine of 23 pneumothorax
patients were diagnosed by chest X-ray. Sensitivity and specificity of PA chest X
ray in the diagnosis of pneumothorax was 39.1% and 100%, respectively. Positive
predictive values of chest X-ray for diagnosis of pneumothorax was 100% and
negative predictive value was 97.1%. Twenty-four patients had pleural effusions
on CT scans, while only 15 could be diagnosed in chest X-rays. Chest X-rays were
62.5% sensitive and 100% specific with positive and negative predictive values of
100% and 98.1%, respectively. Twenty of 41 rib fractures were diagnosed with X
rays. Chest x rays had a 48.8% sensitivity and 100% specificity, and positive and
negative predictive values were 100% and 95.6%, respectively. CONCLUSION: Chest X
ray should not be used as a sole diagnostic imaging tool for exclusion of
pneumothorax, hemothorax, and lung contusion. Due to high predictive values of
chest X-rays, they can be used for follow-up.
PMID- 29950262
TI - The Relationship between Burnout, Self-Esteem and Professional Life Quality of
Nurses.
AB - OBJECTIVE: To evaluate the correlation between burnout, self-esteem and quality
of life among nurses. STUDY DESIGN: Analytical, cross-sectional study. PLACE AND
DURATION OF STUDY: Sakarya Training and Research Hospital, Turkey, in 2013.
METHODOLOGY: The sample was made-up of 131 volunteering nurses after obtainnig
informed written consent from the participants, ethical committee, and
corresponding institutions. Data were collected by personal information form (21
questions), Maslach Burnout Inventory (MBI-22 items), Rosenberg Self-Esteem Scale
(RSES-10 items), Professional Quality Of Life Scale(ProQOL-30 items). RESULTS:
The scales were analysed in terms of internal consistency. Cronbach Alpha
coefficients were determined as reliable for our sample. MBI 3 subscale total
scores of the participant nurses were low for emotional exhaustion and
depersonalization, high for personal accomplishment. Total score from RSES was
15.32 +/-3.70. Total scores from 3 subscales of ProQOL were 29.78 +/-9.02 for
compassion satisfaction, 24.65 +/-5.75 for burnout, and 15.12 +/-6.54 for
compassion fatigue. CONCLUSION: In this study, it was detected that burnout in
nurses affected compassion satisfaction and individual success negatively.
PMID- 29950263
TI - Postoperative Complications of Endoscopic Versus Microscopic Transsphenoidal
Pituitary Surgery: A Meta-Analysis.
AB - Transsphenoidal microscopic pituitary surgery is an effective way of treating
pituitary tumors. However, minimal invasive approach endoscopic transsphenoidal
pituitary surgery has become much more prevalent these days. Endoscopic surgery
resects the maximum tumour with less complications. As endoscopic surgery is much
safer and less invasive as compared to the microscopic transsphenoidal surgery,
selection of technology for the treatment of pituitary adenoma is becoming
increasingly equivocal. The main aim of this systematic review was to assess the
safety of endoscopic and microscopic transsphenoidal pituitary surgery in terms
of postoperative complications. Relevant studies between January 1992 and January
2017 were searched in the Cochrane Library electronic databases, EMBASE and
MEDLINE, through a systematic literature search. A total of 1,463 patients
reviewed (microscopic group=684, endoscopic group=779), the proportion of
diabetes insipidus, septal perforation and other complications related to surgery
(include lip anesthesia, nasal anesthesia, deviated septum, saddle nose,
sinusitis, synechiae, anosmia) in those patients who had endoscopic surgery were
significantly lower (p<0.05). No significant difference emerged between the two
approaches in the incidence rates of cerebrospinal fluid leak, meningitis,
epistaxis or hypopituitarism (p>0.05). These results support the safety of
endoscopic transsphenoidal pituitary adenoma surgery.
PMID- 29950264
TI - Cost-effectiveness of Screening and Confirmatory Tests for Multiple Myeloma in
Pakistani Population: An Audit Report.
AB - OBJECTIVE: To find out the use of screening and confirmatory tests for diagnosis
of multiple myeloma as ordered by clinicians. STUDY DESIGN: An Audit. PLACE AND
DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed
Forces Institute of Pathology, Rawalpindi, from January 2012 to January 2017.
METHODOLOGY: Data retrieved from Laboratory Information Management system (LIMs)
by selecting serum protein electrophoresis (SPE) as screening test and
immunoelectophoresis (IE) and immunofixation (IF) as confirmatory tests. RESULTS:
There were 3,108 tests of serum protein electrophoesis and 1,329 tests of
immunoelectophoresis had been performed in last five year. Cost-effective
clinical audit of SPE tests showed that only 17.1% tests of SPE were either used
for proper diagnosis of multiple myeloma (totally justified tests 13%) or useful
for diagnosis of other important diseases whose early diagnosis were helpful for
patients management (partially justified tests 4.1%). The cost related to these
tests were justified while 82.8% tests of SPE were either normal (total
unjustified tests 24.4%), or diagnosed irrevalent and nonspecific diseases
(partially unjustified 58.4%). IE and IF audit revealed that only 26.6% tests
were properly utilised for diagnosis and differentiation of multiple myeloma and
its subtypes and cost attributable to these tests were justified while 73.4% of
these confirmatory tests were normal and cost related to them was not justified.
CONCLUSION: Overutilisation of laboratory tests for diagnosis of multiple myeloma
can be minimised by proper clinical scrutiny of request forms.
PMID- 29950265
TI - Solitary Fibrous Tumor of Kidney.
AB - Solitary fibrous tumor of kidney is an unusual condition. It is spindle cell
tumor with mesenchymal in origin so most commonly reported cases are in pleura,
and extra-pleural sites are very rare. It is mostly benign in nature but
malignant variant are also reported. Treatment is en bloc resection as in other
sites whether pleural or extra-pleural. Prognosis is excellent. This tumor is
difficult to diagnose only on imaging features; so for diagnosis, histopathology
is needed mostly with immunohistochemical markers like CD34, CD99, Bcl2 proteins.
A middle-aged male presented initially with clinical and radiological features,
suspected of renal cell carcinoma. Surgery was performed, which proved solitary
fibrous tumor on histopathology; and patient on follow-up remained tumor-free
till the last follow-up.
PMID- 29950266
TI - Tuberculous Paraspinal Abscess Invading Esophagus: A Rare Cause of Dysphagia.
AB - Esophageal involvement by mycobacterium tuberculosis is a rare entity even in the
endemic regions. The common presenting complaint in esophageal tuberculosis are
deglutition disorders in which patients primarily present with difficulty in
swallowing. The most common site of esophageal involvement is the middle-third at
the level of carina. Herein, the case of an adolescent boy is presented who had
complains of dysphagia, abdominal pain along with weight loss for a month. On
evaluation, he was found to have esophageal narrowing resulting in dysphagia. CT
scan revealed a fistulous communication of tuberculous paraspinal abscess with
the esophagus, which had resulted in dysphagia. The diagnosis of tuberculosis was
made by using gold standard method of Polymerase Chain Reaction (PCR) of
mycobacterium tuberculosis. He had marked symptomatic improvement within a month
of starting anti tuberculous therapy (ATT) and was successfully treated with ATT
for 9 months.
PMID- 29950267
TI - Enteroenteric Fistulae in Acute Bowel Ischemia.
AB - Gastrointestinal fistulae are classified as enteroenteric or enterocutaneous.
Most gastrointestinal fistulae are formed after surgical procedures for
inflammatory bowel disease or malignancy. For spontaneous enteroenteric fistulae,
ischemia has been reported as a possible etiology. We report two cases of
spontaneous enteroenteric fistulae arising after bowel ischemia; a 38-year male
with a 10-day history of severe abdominal pain with fever and vomiting, and a 22
year female with a one-week history of abdominal pain and diarrhea. Arterial and
venous thrombi in association with enteroenteric fistulae were identified on
computed tomography. These cases point towards acute mesenteric ischemia as a
rare cause of spontaneous enteroenteric fistulae. Surgical management of these
fistulae can be effective in resolving this complication.
PMID- 29950268
TI - Cranially Migrated Ventriculoperitoneal Shunt in Patient with Bilateral Subdural
Empyema.
AB - A right-sided ventriculoperitoneal (VP) shunt was placed in patient with
congenital hydrocephalous in the first month of life. Three-month review visit
showed no improvement and after evaluation and computerised tomogram (CT) scan
brain, another VP shunt was placed on the left side without handling the previous
right sided VP shunt. Patient did not improve and again presented with fever and
fits. CT scan brain with and without contrast was repeated, which showed
bilateral subdural empyema and right-sided cranially migrated VP shunt.
Cerebrospinal fluid (CSF) analysis demonstrated infection. Bilateral burr hole
drainage of subdural empyema with subsequent removal of right-sided migrated VP
shunt was done. Cranial end of left-sided VP shunt was converted into external
ventricular drain (EVD) and its abdominal end removed. Patient was placed on
intravenous as well as intraventricular antibiotics through the EVD. Later, right
sided VP shunt was placed after clearance of infection. Regular follow-up showed
that the patient is doing well.
PMID- 29950269
TI - Aspirin in Primary Prevention of Myocardial Infarction/Angina and Stroke in
Hypertensive Patients.
PMID- 29950270
TI - Peripheral Ameloblastic Fibroma of Anterior Maxillary Gingiva Simulating Pyogenic
Granuloma.
PMID- 29950271
TI - Cancer Rehabilitation: Emerging Role of Physiatrists in a Multi-Disciplinary
Cancer Care Team.
PMID- 29950272
TI - Religion/Spirituality: A Tool to Better Help Psychiatric Patients.
PMID- 29950273
TI - Correlates of immune exacerbations in leprosy.
AB - Leprosy is still a considerable health threat in pockets of several low and
middle income countries worldwide where intense transmission is witnessed, and
often results in irreversible disabilities and deformities due to delayed- or
misdiagnosis. Early detection of leprosy represents a substantial hurdle in
present-day leprosy health care. The dearth of timely diagnosis has, however,
particularly severe consequences in the case of inflammatory episodes, designated
leprosy reactions, which represent the major cause of leprosy-associated
irreversible neuropathy. There is currently no accurate, routine diagnostic test
to reliably detect leprosy reactions, or to predict which patients will develop
these immunological exacerbations. Identification of host biomarkers for leprosy
reactions, particularly if correlating with early onset prior to development of
clinical symptoms, will allow timely interventions that contribute to decreased
morbidity. Development of a point-of-care (POC) test based on such correlates
would be a definite game changer in leprosy health care. In this review,
proteomic-, transcriptomic and metabolomic research strategies aiming at
identification of host biomarker-based correlates of leprosy reactions are
discussed, next to external factors associated with occurrence of these episodes.
The vast diversity in research strategies combined with the variability in
patient- and control cohorts argues for harmonisation of biomarker discovery
studies with geographically overarching study sites. This will improve
identification of specific correlates associated with risk of these damaging
inflammatory episodes in leprosy and subsequent application to rapid field tests.
PMID- 29950274
TI - Effect of UV-B radiation on morphology, phenolic compound production, gene
expression, and subsequent drought stress responses in chili pepper (Capsicum
annuum L.).
AB - It has been suggested that accumulation of flavonoids could be a key step in
development of plant tolerance to different environmental stresses. Moreover, it
has been recognized that abiotic stresses such as drought and UV-B radiation (280
315 nm) induce phenolic compound accumulation, suggesting a role for these
compounds in drought tolerance. The aim of the present study was to evaluate the
effect of UV-B exposure on chili pepper (Capsicum annuum, cv. 'Coronel') plant
performance, phenolic compound production, and gene expression associated with
response to subsequent drought stress. Additionally, the phenotypic response to
drought stress of these plants was studied. UV-B induced a reduction both in stem
length, stem dry weight and number of floral primordia. The largest reduction in
these variables was observed when combining UV-B and drought. UV-B-treated well
watered plants displayed fructification approximately 1 week earlier than non-UV
B-treated controls. Flavonoids measured epidermally in leaves significantly
increased during UV-B treatment. Specifically, UV-B radiation significantly
increased chlorogenic acid and apigenin 8-C-hexoside levels in leaves and a
synergistic increase of luteolin 6-C-pentoside-8-C-hexoside was obtained by UV-B
and subsequent drought stress. Gene expression of phenylalanine ammonia lyase
(PAL) and chalcone synthase (CHS) genes also increased during UV-B treatments. On
the other hand, expression of genes related to an oxidative response, such as
mitochondrial Mn-superoxide dismutase (Mn-SOD) and peroxidase (POD) was not
induced by UV-B. Drought stress in UV-B-treated plants induced mitochondrial Mn
SOD gene expression. Taken together, the UV-B treatment did not induce
significant tolerance in plants towards drought stress under the conditions used.
PMID- 29950275
TI - Prognostic factors for patients with accidental hypothermia: A multi
institutional retrospective cohort study.
AB - INTRODUCTION: In cases of severe accidental hypothermia (AH) in urban areas, the
prognostic factors are unknown. We identified factors associated with in-hospital
mortality in patients with moderate-to-severe AH in urban areas of Japan. METHOD:
The J-Point registry database is a multi-institutional retrospective cohort study
for AH in 12 Japanese emergency departments. From this registry, we enrolled
patients whose core body temperature was 32 degrees C or less on admission. In
hospital death was the primary outcome of this study. We investigated the
association between each candidate prognostic factor and in-hospital death by
applying the multivariate logistic regression analyses with adjusted odds ratios
(AORs) and their 95% confidence interval [CI] as the effect variables. RESULTS:
Of 572 patients registered in the J-point registry, 358 hypothermic patients were
eligible for analyses. Median body temperature was 29.2 degrees C (interquartile
range, 27.0 degrees C-30.8 degrees C). In-hospital deaths comprised 26.3%
(94/358) of all study patients. Factors associated with in-hospital death were
age >= 75 years (AOR, 3.09; 95% CI, 1.31-7.27), need for assistance with
activities of daily living (ADL; AOR, 3.06; 95% CI, 1.68-5.59), hemodynamic
instability (AOR, 2.49; 95% CI, 1.32-4.68), and hyperkalemia (>=5.6 mEq/L; AOR,
2.65; 95% CI, 1.13-6.21). CONCLUSION: The independent prognostic factors
associated with in-hospital mortality of patients with moderate-to-severe AH in
urban areas of Japan were age >= 75 years, need for assistance with ADL,
hemodynamic instability, and hyperkalemia.
PMID- 29950276
TI - Usefulness of the vibration perception thresholds measurement as a diagnostic
method for diabetic peripheral neuropathy: Results from the Rio de Janeiro type 2
diabetes cohort study.
AB - AIMS: To investigate the associated factors with the vibration threshold
perception (VPT) in patients with type 2 diabetes and to assess whether it is
useful for detection of diabetic peripheral neuropathy (DPN). METHODS: VPTs were
measured with Vibration Sensory Analyzer (VSA-3000) in 426 diabetic patients. The
diagnosis of DPN was based on Neuropathy Symptom Score and Neuropathy Disability
Score (NDS). ROC curve analysis and multiple linear and logistic regressions were
performed to investigate the associations between VPT and DPN. RESULTS: Values of
VPT were progressively higher according to NDS stages. Age, height, diabetes
duration, and mean cumulative HbA1c exposure (partial correlation coefficients:
0.34; 0.27; 0.10; and 0.13; respectively) were the variables independently
associated with VPT. Area under ROC curve of VPT for detection of DPN was 0.71
(95% CI: 0.66-0.75) and >8.9 MUm was its best cut-off value. VPT, age, female
sex, height, diabetes duration and mean HbA1c levels were the independent
correlates of the presence of DPN. An increased VPT triplicate the likelihood of
having DPN (OR: 3.24; 95% CI: 2.05-5.11). CONCLUSIONS: VPT, measured by an
automatic device, shares common correlates with DPN and is strongly associated
with its presence. VPT testing may be useful as a screening tool for DPN
assessment.
PMID- 29950277
TI - Dosimetric comparison of TomoDirect, helical tomotherapy, VMAT, and ff-IMRT for
upper thoracic esophageal carcinoma.
AB - BACKGROUND: The new TomoDirect (TD) modality offers a nonrotational option with
discrete beam angles. We aim to compare dosimetric parameters of TD, helical
tomotherapy (HT), volumetric-modulated arc therapy (VMAT), and fixed-field
intensity-modulated radiotherapy (ff-IMRT) for upper thoracic esophageal
carcinoma (EC). METHODS: Twenty patients with cT2-4N0-1M0 upper thoracic
esophageal squamous cell carcinoma (ESCC) were enrolled. Four plans were
generated using the same dose objectives for each patient: TD, HT, VMAT with a
single arc, and ff-IMRT with 5 fields (5F). The prescribed doses were used to
deliver 50.4 Gy/28F to the planning target volume (PTV50.4) and then provided a 9
Gy/5F boost to PTV59.4. Dose-volume histogram (DVH) statistics, dose uniformity,
and dose homogeneity were analyzed to compare treatment plans. RESULTS: For
PTV59.4, the D2, D98, Dmean, and V100% values in HT were significantly lower than
other plans (all p < 0.05), and those in TD were significantly lower than VMAT
and ff-IMRT (all p < 0.05). However, there was no significant difference in the
D2 and Dmean values between VMAT and ff-IMRT techniques (p > 0.05). The
homogeneity index (HI) differed significantly for the 4 techniques of TD, HT,
VMAT, and ff-IMRT (0.03 +/- 0.01, 0.02 +/- 0.01, 0.06 +/- 0.02, and 0.05 +/-
0.01, respectively; p < 0.001). The HI for TD was similar to HT (p = 0.166), and
had statistically significant improvement compared to VMAT (p < 0.001) and ff
IMRT (p = 0.003). In comparison with the 4 conformity indices (CIs), there was no
significant difference (p > 0.05). For PTV50.4, the D2 and Dmean values in HT
were significantly lower than other plans (all p < 0.05), and those in TD were
significantly lower than VMAT and ff-IMRT (all p < 0.05). However, there was no
significant difference in the D2 and Dmean values between VMAT and ff-IMRT
techniques (p > 0.05). No D98 and V100% parameters differed significantly among
the 4 treatment types (p > 0.05). HT plans were provided for statistically
significant improvement in HI (0.03 +/- 0.01) compared to TD plans (0.05 +/-
0.01, p = 0.003), VMAT (0.08 +/- 0.03, p < 0.001), ff-IMRT (0.08 +/- 0.01, p <
0.001). The HI revealed that TD was superior to VMAT and ff-IMRT (p < 0.05). The
CI differed significantly for the 4 techniques of TD, HT, VMAT, and ff-IMRT (0.59
+/- 0.10, 0.69 +/- 0.11, 0.64 +/- 0.09, and 0.64 +/- 0.11, respectively; p =
0.035). The best CI was yielded by HT. We found no significant difference for the
V5, V10, V15, V30, and the mean lung dose (MLD) among the 4 techniques (all p >
0.05). However, the V20 differed significantly among TD, HT, VMAT, and ff-IMRT
(21.50 +/- 7.20%, 19.50 +/- 5.55%, 17.65 +/- 5.45%, and 16.35 +/- 5.70%,
respectively; p = 0.047). Average V20 for the lungs was significantly improved by
the TD plans compared to VMAT (p = 0.047), and ff-IMRT (p = 0.008). The V5 value
of the lung in TD was 49.30 +/- 13.01%, lower than other plans, but there was no
significant difference (p > 0.05). The D1 of the spinal cord showed no
significant difference among the 4 techniques (p = 0.056). CONCLUSIONS: All
techniques are able to provide a homogeneous and highly conformal dose
distribution. The TD technique is a good option for treating upper thoracic EC
involvement. It could achieve optimal low dose to the lungs and spinal cord with
acceptable PTV coverage. HT is a good option as it could achieve quality dose
conformality and uniformity, while TD generated superior conformality.
PMID- 29950278
TI - Frailty predicts short-term survival even in older adults without multimorbidity.
AB - BACKGROUND: Frailty and multimorbidity are both strongly associated with poor
health-related outcomes, including mortality. Being multimorbidity one of the
major determinants of frailty, we aimed to explore whether, and to what extent,
frailty without multimorbidity plays an independent role in shortening life.
METHODS: We used data from the Swedish National Study on Aging and Care in
Kungsholmen (SNAC-K). Among the 3363 adults aged 60+ enrolled at baseline, those
without multimorbidity (i.e.: less than two chronic diseases) (N = 1115) have
been characterized according to Fried's frailty phenotype (i.e. robust, prefrail,
and frail). The association between frailty and mortality was estimated using
piecewise proportional hazard regression models in three five-year time periods.
RESULTS: Among participants without multimorbidity, 424 (38%) were prefrail and
19 (2%) were frail. During the 15-year follow-up, 263 (24%) participants died:
19%, 29%, and 63% of those who were robust, prefrail, and frail at baseline,
respectively. Within the first 5 years of follow-up, prefrail and frail
participants had more than doubled mortality risk in comparison to robust ones
(HR for pre-frailty 2.08, 95% CI 1.15-3.76; HR for frailty 2.69, 95% CI 1.22
5.97). Beyond 5 years, a trend of increased mortality rate was still detectable
for prefrail and frail subjects in comparison to robust ones. CONCLUSIONS:
Physical frailty and pre-frailty are associated with short-term mortality in a
cohort of older adults free from multimorbidity. Frailty could be a clinical
indicator of increased risk of negative health outcomes even among subjects
without multiple chronic conditions.
PMID- 29950279
TI - Depression of lymphocyte activity during cutaneous leishmaniasis: a case report.
AB - Skin leishmaniasis includes lesions of different appearance, shape, and severity,
spanning from alarming diffuse lesions to an asymptomatic course. Moreover,
aspecific presentation, as well as challenging differential diagnosis of
cutaneous leishmaniasis, may request more in-depth investigations on the
intriguing and complex pathogenesis of such infection. A 7-year case of worsening
cutaneous leishmaniasis in the left frontoparietal region of the scalp, achieving
omolateral eyebrow, in a 68-year-old male patient prompted us to address the
immunity profile of peripheral blood lymphocytes. An increase of regulatory
CD19+/CD38bright/CD24bright B cell lymphocytes was observed at the front of
normal levels of other lymphocytes subpopulations, including CD4+/CD25bright T
cells. The total IgG and IgM, as well as proinflammatory subclasses of IgG, were
below the normal range. However, IgG4 subclass was found normal. In conclusion,
our data may indicate inhibition of humoral immunity associated with an increase
of lymphocyte B-regulatory subpopulation.
PMID- 29950280
TI - Role of progesterone concentrations during early follicular development in beef
cattle: II. Ovulatory follicle growth and pregnancy rates.
AB - Two experiments were conducted to investigate the role of relatively lesser and
greater progesterone (P4) concentrations during early follicular development on
ovulatory follicle growth and pregnancy rate in beef cattle. In Experiment 1,
time of ovulation was synchronized with the 5 d CO-Synch + CIDR (Controlled
Internal Drug Release) program in multiparous cows (n = 241). Six days after the
2nd GnRH injection of the pre-synchronization program (d 0), ablation of
follicles >= 5 mm in the ovaries was performed and cows were assigned to receive
either a previously used CIDR and 2x-25 mg PGF2alpha doses 8 h apart (LoP4), or a
new CIDR (HiP4). On d 5, CIDR were removed from all cows, 2x-25 mg PGF2alpha were
administered, and estrous detection tail paint was applied. Timed artificial
insemination (TAI) was performed on d 8. On d 5, P4 concentrations were greater
(P < 0.01) in the HiP4 (4.9 +/- 0.13 ng/mL) than LoP4 (1.0 +/- 0.06 ng/mL)
treatment group. Conversely, d 5 estradiol (E2) concentrations and follicular
diameter were greater (P < 0.01) in the LoP4 (5.0 +/- 0.23 pg/mL and 8.9 +/-
0.20 mm) than HiP4 (1.5 +/- 0.12 pg/mL and 7.4 +/- 0.15 mm) treatment group.
Follicular diameter at TAI (12.0 +/- 0.12 mm, Table 1) and TAI pregnancy rate did
not differ (P > 0.10) between treatment groups. In Experiment 2, a new
follicular wave was induced with estradiol benzoate on d -7, and cows (n = 275)
were assigned on d 0 to receive 25 mg PGF2alpha and either have the CIDR replaced
with a new CIDR (HiP4) or the used CIDR was left in place (LoP4).Furthermore, all
cows received GnRH on d 0. The CIDRs were removed from all cows on d 5 and two
doses of -25 mg PGF2alpha were administered. Estrous detection combined with AI
12 h later (Estrus-AI) was performed for 60 h after CIDR removal with TAI coupled
with GnRH administration at 72 h if estrus was not detected. The concentrations
of P4 on d 5 were greater (P < 0.01) in the HiP4 (2.8 +/- 0.10 ng/ml) than LoP4
(1.7 +/- 0.05 ng/mL) treatment group. For cows that were detected in estrus after
PGF2alpha administration, estrous response (83.5%) and interval to estrus (55.0
+/- 0.5 h) did not differ between treatment groups. Pregnancy rate (combined
Estrus-AI and TAI) that resulted from breeding at the time of the synchronized
time of estrus was similar between treatment groups (HiP4: 77.1%; LoP4: 82.3%).
In conclusion, differences in P4 concentrations during early follicular
development do not effect pregnancy rate in beef cows when the cows are
inseminated at the time of a synchronized estrus if the cows have similar
intervals of proestrus.
PMID- 29950281
TI - The treatment with selenium increases placental parasitismin pregnant Wistar rats
infected with the Y strain of Trypanosoma cruzi.
AB - Selenium (Se) is an essential micronutrient in the diet of mammals and has an
important role in the immune function. Selenium is a key element in
selenoproteins involved in the in the maintenance of the antioxidant defense.
Diet with selenium is beneficial for the treatment of diseases correlated with
high levels of oxidative stress, also observed in the Chagas disease. Chagas
disease is a neglected disease caused by the protozoan Trypanosoma cruzi and
several research groups are focused on the illness treatment. Immunomodulation of
the infection using microelements is an important tool to avoid deleterious
effects of the Chagas disease. Therefore, our objective was to evaluate the
effects of selenium supplementation on pregnant Wistar rats infected with T.
cruzi. Selenium treatment stimulated the weight and length of fetuses and
placentas allied to the decrease of blood parasitemia. However, selenium
demonstrated a low influence on T cells, diminishing the B cell population
(CD45RA+). Moreover, the production of pro-inflammatory cytokines was
downregulated under selenium administration. Low pro-inflammatory cytokines
levels probably are related to the increase in the number of amastigote nests in
infected and treated animals. Thus, selenium supplementation during pregnancy
could impair the local placental immune response. Further studies are necessary
to assess the interaction between selenium and the acute Chagas' disease during
pregnancy, which will base future supplementation strategies.
PMID- 29950282
TI - Impact of age, comorbidity and WHO performance status on delay of treatment in
patients undergoing fast-track work-up for head and neck cancer.
AB - OBJECTIVES: Fast-track programs for diagnostic work-up and start of cancer
treatment are defined by legislation in Denmark. The aim was to examine whether
age, comorbidity or WHO performance status influence the time from referral due
to suspicion of cancer to start of treatment (waiting time) in the Danish fast
track program. MATERIAL AND METHODS: For this descriptive cohort study,
consecutive head and neck cancer (HNC) patients who underwent radiotherapy or
surgery from January 2014 to July 2016 at Odense University Hospital (OUH) were
identified in the database of the Danish Head and Neck Cancer group (DAHANCA).
Age (<70 vs. >=70 years), comorbidity (none vs. any), and WHO performance status
(0-1 vs. 2-4) were correlated to waiting time. RESULTS: In total, 650 HNC
patients were included and of those, 92% were discussed at the multidisciplinary
team conference. Patients >=70 years were less frequently discussed in a
multidisciplinary setting compared to younger patients (88% vs. 93%, p < 0.05).
The time spent for diagnostic workup and treatment planning (waiting time) was
longer for patients having primary radiotherapy than for primary surgery (p <
0.001), and 21% of patients treated with primary radiation exceeded the
recommended maximum waiting time, whereas this was the case for only 7% of the
patients treated with primary surgery. However, age >= 70 years, presence of
comorbidity or poor performance status did not significantly influence the
waiting time. CONCLUSION: Age >= 70 years, comorbidity and poor WHO performance
status did not influence the waiting time among patients with head and neck
cancer treated at OUH.
PMID- 29950283
TI - The timing of onset of hypertensive disorders in pregnancy and the risk of
incident hypertension and cardiovascular disease.
AB - BACKGROUND: Previous studies suggest that women with hypertensive disorders of
pregnancy (HDP) are at increased risk of subsequent cardiovascular disease (CVD).
However, it is unclear whether this association differs by timing of onset of
HDP. METHODS: A population-based cohort of 146,748 women, aged 15-45 years, with
a first recorded pregnancy were identified in the Clinical Practice Research
Datalink. HDP were defined between 18 weeks gestation and 6 weeks postpartum and
further sub-classified as early- (<34 weeks) and late-onset HDP (>=34 weeks). The
primary outcome was incident CVD, and the secondary outcome was incident
hypertension. We used marginal structural Cox models to account for time-varying
exposure and confounding. RESULTS: Compared with women with no HDP, those with
early-onset HDP had a higher risk of developing incident CVD (HR 2.6, 95% CI 1.5,
4.3) and hypertension (HR 4.3, 95% CI 3.6, 5.0). Wide CIs precluded any
conclusions regarding a difference in the risk of incident CVD and hypertension
in women with early- vs late-onset HDP (HR 0.90, 95% CI 0.50, 1.62 and HR 1.06,
95% CI 0.87, 1.28, respectively). CONCLUSION: HDP in at least one pregnancy was
associated with an increased risk of subsequent CVD or hypertension, irrespective
of time of diagnosis.
PMID- 29950284
TI - Development and implementation of participant safety plans for international
research with stigmatised populations.
AB - People who inject drugs with high-risk sharing practices have high rates of HIV
transmission and face barriers to HIV care. Interventions to overcome these
barriers are needed; however, stigmatisation of drug use and HIV infection leads
to safety concerns during the planning and conduct of research on such
interventions. In preparing to address concerns about safety and wellbeing of
participants in an international research study, HIV Prevention Trials Network
074, we developed participant safety plans (PSPs) at each site to supplement
local research ethics committee oversight, community engagement, and usual
clinical trial procedures. The PSPs were informed by systematic local legal and
policy assessments, and interviews with key stakeholders. After PSP refinement
and implementation, we assessed social impacts at each study visit to ensure
continued safety. Throughout the study, five participants reported a negative
social impact, with three resulting from study participation. Future research
with stigmatised populations should consider using and assessing this approach to
enhance safety and welfare.
PMID- 29950285
TI - Prostate cancer: Basics on clinical appearance, diagnostics and treatment.
AB - With an incidence of approximately 60,000 per year prostate cancer is the most
common malignant neoplasm in men with a relatively low mortality rate and a high
mean age of primary diagnosis of about 70 years. The disease remains usually
clinically occult over a long period of time and generally manifests primarily in
a locally advanced or metastasized stage. Due to screening using the PSA level
(prostate specific antigen) in blood serum, diagnosis and therapy nowadays are
oftentimes possible at an early stage. The prostate carcinoma is classified using
risk groups based on the level of PSA, the local tumor spread and the
histological degree of differentiation (Gleason score). If no metastases are
detected during staging a local curative therapy is indicated, provided that the
patient is eligible for this due to age, comorbidity and life expectancy.
Depending on the risk group of the patient, radical prostatectomy, percutaneous
radiotherapy, brachytherapy or active surveillance are available as curative
therapy concepts. Focal therapies such as HIFU, electrovaporization or
cryotherapy are currently considered to be experimental. If metastases are
already present at primary diagnosis, palliative, systemic therapy can be
performed with an androgen deprivation therapy and chemotherapy. At an advanced
and hormone refractory stage, treatment with an osteotropic radiotracer or
palliative radiotherapy can reduce bone metastases and alleviate respective
symptoms.
PMID- 29950286
TI - Erratum: "Projecting Age-Stratified Risk of Exposure to Inland Flooding and
Wildfire Smoke in the United States under Two Climate Scenarios".
AB - [This corrects the article DOI: https://doi.org/10.1289/EHP2594.].
PMID- 29950287
TI - Metabolic Effects of a Chronic Dietary Exposure to a Low-Dose Pesticide Cocktail
in Mice: Sexual Dimorphism and Role of the Constitutive Androstane Receptor.
AB - BACKGROUND: Epidemiological evidence suggests a link between pesticide exposure
and the development of metabolic diseases. However, most experimental studies
have evaluated the metabolic effects of pesticides using individual molecules,
often at nonrelevant doses or in combination with other risk factors such as high
fat diets. OBJECTIVES: We aimed to evaluate, in mice, the metabolic consequences
of chronic dietary exposure to a pesticide mixture at nontoxic doses, relevant to
consumers' risk assessment. METHODS: A mixture of six pesticides commonly used in
France, i.e., boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram,
was incorporated in a standard chow at doses exposing mice to the tolerable daily
intake (TDI) of each pesticide. Wild-type (WT) and constitutive androstane
receptor-deficient (CAR-/-) male and female mice were exposed for 52 wk. We
assessed metabolic parameters [body weight (BW), food and water consumption,
glucose tolerance, urinary metabolome] throughout the experiment. At the end of
the experiment, we evaluated liver metabolism (histology, transcriptomics,
metabolomics, lipidomics) and pesticide detoxification using liquid
chromatography-mass spectrometry (LC-MS). RESULTS: Compared to those fed control
chow, WT male mice fed pesticide chow had greater BW gain and more adiposity.
Moreover, these WT males fed pesticide chow exhibited characteristics of hepatic
steatosis and glucose intolerance, which were not observed in those fed control
chow. WT exposed female mice exhibited fasting hyperglycemia, higher reduced
glutathione (GSH):oxidized glutathione (GSSG) liver ratio and perturbations of
gut microbiota-related urinary metabolites compared to WT mice fed control chow.
When we performed these experiments on CAR-/- mice, pesticide-exposed CAR-/-
males did not exhibit BW gain or changes in glucose metabolism compared to the
CAR-/- males fed control chow. Moreover, CAR-/- females fed pesticide chow
exhibited pesticide toxicity with higher BWs and mortality rate compared to the
CAR-/- females fed control chow. CONCLUSIONS: To our knowledge, we are the first
to demonstrate a sexually dimorphic obesogenic and diabetogenic effect of chronic
dietary exposure to a common mixture of pesticides at TDI levels, and to provide
evidence for a partial role for CAR in an in vivo mouse model. This raises
questions about the relevance of TDI for individual pesticides when present in a
mixture. https://doi.org/10.1289/EHP2877.
PMID- 29950288
TI - An Online Hand Exercise Intervention for Adults With Rheumatoid Arthritis
(mySARAH): Design, Development, and Usability Testing.
AB - BACKGROUND: The Strengthening and Stretching for Rheumatoid Arthritis of the Hand
(SARAH) program is a tailored, progressive 12-week exercise program for people
with hand problems due to rheumatoid arthritis. The program was shown to be
clinically and cost-effective in a large clinical trial and is recommended by the
UK National Institute for Health and Care Excellence (NICE) guidelines for
rheumatoid arthritis in adults. OBJECTIVE: We have developed an online version of
the SARAH program (mySARAH) to make the SARAH program widely accessible to people
with rheumatoid arthritis. The purposes of this study were to develop mySARAH and
to evaluate and address its usability issues. METHODS: We developed mySARAH using
a three-step process and gaining feedback from patient contributors. After
initial development, mySARAH was tested in two iterative usability cycles in nine
participants using a simplified think-aloud protocol and self-reported
questionnaires. We also evaluated if participants executed the SARAH exercises
correctly after watching the exercise videos included on the website. RESULTS: A
preliminary version of mySARAH consisting of six sessions over a 12-week period
and delivered via text, exercise videos, images, exercise plan form, exercise
calendar, and links to additional information on rheumatoid arthritis was
developed. Five participants (1 male; 4 females; median age 64 years) and four
participants (four females; median age 64.5 years) took part in the first and
second usability testing cycles respectively. Usability issues identified from
Cycle 1 such as having a navigation tutorial video and individualised feedback on
pain levels were addressed prior to Cycle 2. The need for more instructions to
complete the mySARAH patient forms was identified in Cycle 2 and was rectified.
Self-reports from both cycles indicated that participants found the program
useful and easy to use and were confident in performing the SARAH exercises
themselves. Eight of the nine participants correctly demonstrated all the
exercises. CONCLUSIONS: mySARAH is the first online hand exercise intervention
for people with rheumatoid arthritis. We actively involved target users in the
development and usability evaluation and ensured mySARAH met their needs and
preferences.
PMID- 29950290
TI - Effects of the Digital Transformation: Qualitative Study on the Disturbances and
Limitations of Using Video Visits in Outpatient Care.
AB - BACKGROUND: Video mediated meetings with patients were introduced in outpatient
care at a hospital in Sweden. New behaviours and tasks emerged due to changes of
roles, work processes and responsibilities. The study investigates effects of
digital transformation, in this case how video visits in outpatient care change
work processes and introduces new tasks, in order to further improve the concept
of video visits. OBJECTIVE: Through real-time, social interactional features of
preparing for and conducting video visits, the study examines clinicians'
perceived limitations and disturbances, and how the conditions between patients
and clinicians may change when using video visits instead of face-to-face
meetings in outpatient care. METHODS: Qualitative methods have been used
including 14 observations of video visits at two different clinics and 14
followup interviews with clinicians. Transcriptions of interviews and field notes
were thematically analysed, discussed and synthesised into themes. RESULTS:
Disturbances and limitations related to the technology were related to time; a
flexibility to schedule the meeting unbound of place, frustrations when the other
part was late for the scheduled meeting, and that more experienced users of video
visits usually waited longer before logging in. They were also related to sound;
problems getting the sound to work satisfactory during the video visits, and
problems with the image. Disturbances and limitations related to the surroundings
were related to both the patient's and the clinician's environment; the principle
of video technology in itself may affect the experience and the content of the
consultation, and the surrounding chosen changes the conditions for and reduces
the participants' field of view. CONCLUSIONS: We could see 1) a transformation of
roles and responsibilities when turning from face-to-face meetings to video
visits, 2) that video visits add new circumstances, with a risk of introducing
disturbances and limitations, that in turn affects the content of the meeting, 3)
that avoiding negative disturbances during a video visit, requires a sensibility
from the clinician's side as well as a trust in the patient's judgement, 4) that
both expected and unexpected disturbances and limitations during a video visit
affect the clinician's behaviour, feelings, the content of the meeting and how
the clinician's relate to the different components of the concept, and 5) that
there is a change of roles introduced when conducting video visits, eg, the
clinician taking the first line support if both (s)he and the patient encounter
problems with the technology.
PMID- 29950291
TI - ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet
release and causes microthrombocytopenia.
AB - Bone marrow (BM) megakaryocytes (MKs) produce platelets by extending proplatelets
into sinusoidal blood vessels. Defects in thrombopoiesis can lead to
thrombocytopenia associated with increased bleeding tendency. Recently, the
platelet disorder congenital autosomal-recessive small-platelet thrombocytopenia
(CARST) was described; it is caused by mutations in the adhesion and
degranulation-promoting adaptor protein (ADAP; synonym: FYB, SLAP130/120) gene,
and characterized by microthrombocytopenia and bleeding symptoms. In this study,
we used constitutive ADAP-deficient mice (Adap-/- ) as a model to investigate
mechanisms underlying the microthrombocytopenia in CARST. We show that Adap-/-
mice display several characteristics of human CARST, with moderate
thrombocytopenia and smaller-sized platelets. Adap-/- platelets had a shorter
life span than control platelets, and macrophage depletion, but not splenectomy,
increased platelet counts in mutant mice to control levels. Whole-sternum 3
dimensional confocal imaging and intravital 2-photon microscopy revealed altered
morphology of ADAP-deficient MKs with signs of fragmentation and ectopic release
of (pro)platelet-like particles into the BM compartment. In addition, cultured BM
derived MKs lacking ADAP showed reduced spreading on extracellular matrix
proteins as well as activation of beta1 integrins, impaired podosome formation,
and displayed defective polarization of the demarcation membrane system in vitro.
MK-/platelet-specific ADAP-deficient mice (PF4-cre) also produced fewer and
smaller-sized platelets and released platelets ectopically. These data
demonstrate that the abnormal platelet production in the mutant mice is an MK
intrinsic defect. Taken together, these results point to an as-yet-unidentified
role of ADAP in the process of MK polarization and platelet biogenesis.
PMID- 29950292
TI - Evolution of a chemosensitive core-binding factor AML into an aggressive leukemia
with eosinophilic differentiation.
PMID- 29950294
TI - Adult social care: specific new tax is needed or NHS funding will suffer, say
MPs.
PMID- 29950293
TI - Do GPs accurately record date of death? A UK observational analysis.
AB - OBJECTIVE: To examine the concordance between dates of death recorded in UK
primary care and national mortality records. METHODS: UK primary care data from
the Clinical Practice Research Datalink were linked to Office for National
Statistics (ONS) data, for 118 571 patients who died between September 2010 and
September 2015. Logistic regression was used to examine factors associated with
discrepancy in death dates between data sets. RESULTS: Death dates matched in
76.8% of cases with primary care dates preceding ONS date in 2.9%, and following
in 20.3% of cases; 92.2% of cases differed by <2 weeks. Primary care date was >4
weeks later than ONS in 1.5% of cases and occurred more frequently with deaths
categorised as 'external' (15.8% vs 0.8% for cancer), and in younger patients
(15.9% vs 1% for 18-29 and 80-89 years, respectively). General practices with the
greatest discrepancies (97.5th percentile) had around 200 times higher odds of
recording substantially discordant dates than practices with the lowest
discrepancies (2.5th percentile). CONCLUSION: Dates of death in primary care
records often disagree with national records and should be treated with caution.
There is marked variation between practices, and studies involving young
patients, unexplained deaths and where precise date of death is important are
particularly vulnerable to these issues.
PMID- 29950295
TI - Providing care based on need and free at point of delivery is NHS's greatest
achievement, say BMJ readers.
PMID- 29950296
TI - Time for a public health campaign encouraging people to talk about death.
PMID- 29950297
TI - Does the intramuscular tendon act like a free tendon?
PMID- 29950298
TI - Risk factors of suicidal ideation in a population of UK military veterans seeking
support for mental health difficulties.
AB - BACKGROUND: Little has been reported regarding the risk factors of suicidal
ideation in individuals once they have left the military in the UK. The aim of
this paper was to explore the risk factors associated with suicidal ideation in a
sample of treatment-seeking veterans. METHODS: Using a cross-sectional design,
participants included veterans (n=144) seeking treatment from a national mental
health charity in the UK. Individuals completed questionnaires regarding their
military experiences, pre-enlistment factors and health. Data were then linked to
risk assessments extracted from clinical records. RESULTS: After controlling for
relevant variables, suicidal ideation was significantly higher in veterans who
were unemployed (OR 8.01; 95% CI 1.79 to 35.80), were early service leavers (OR
8.46; 95% CI 2.21 to 32.35) and those with a history of childhood adversity (OR
6.92; 95% CI 2.10 to 22.82). In addition, taking longer than 5 years to seek help
was associated with a reduced risk of suicidal ideation (OR 0.10; 95% CI 0.06 to
0.87). There was no association between health outcomes and suicidal ideation.
CONCLUSIONS: Risk factors associated with suicidal ideation in this sample of
veterans included: being unemployed, an early service leaver, taking less than 5
years to seek help and experiencing preservice adversity.
PMID- 29950289
TI - Applications of Space Technologies to Global Health: Scoping Review.
AB - BACKGROUND: Space technology has an impact on many domains of activity on earth,
including in the field of global health. With the recent adoption of the United
Nations' Sustainable Development Goals that highlight the need for strengthening
partnerships in different domains, it is useful to better characterize the
relationship between space technology and global health. OBJECTIVE: The aim of
this study was to identify the applications of space technologies to global
health, the key stakeholders in the field, as well as gaps and challenges.
METHODS: We used a scoping review methodology, including a literature review and
the involvement of stakeholders, via a brief self-administered, open-response
questionnaire. A distinct search on several search engines was conducted for each
of the four key technological domains that were previously identified by the UN
Office for Outer Space Affairs' Expert Group on Space and Global Health (Domain
A: remote sensing; Domain B: global navigation satellite systems; Domain C:
satellite communication; and Domain D: human space flight). Themes in which space
technologies are of benefit to global health were extracted. Key stakeholders, as
well as gaps, challenges, and perspectives were identified. RESULTS: A total of
222 sources were included for Domain A, 82 sources for Domain B, 144 sources for
Domain C, and 31 sources for Domain D. A total of 3 questionnaires out of 16 sent
were answered. Global navigation satellite systems and geographic information
systems are used for the study and forecasting of communicable and
noncommunicable diseases; satellite communication and global navigation satellite
systems for disaster response; satellite communication for telemedicine and tele
education; and global navigation satellite systems for autonomy improvement,
access to health care, as well as for safe and efficient transportation. Various
health research and technologies developed for inhabited space flights have been
adapted for terrestrial use. CONCLUSIONS: Although numerous examples of space
technology applications to global health exist, improved awareness, training, and
collaboration of the research community is needed.
PMID- 29950299
TI - Lessons learnt from the Pietermaritzburg experience with damage control
laparotomy for trauma.
AB - INTRODUCTION: The modern concept of damage control surgery (DCS) for trauma was
first introduced less than three decades ago. This audit aims to describe the
spectrum and outcome of patients requiring DCS, to benchmark our experience
against that reported from other centres and countries and to distil the
pertinent teaching lessons from this experience. METHODS: All patients over the
age of 15 years undergoing a laparotomy for trauma over the period from December
2012 to July 2016 were retrieved from the trauma registry of the Pietermaritzburg
Metropolitan Trauma Service, South Africa. Physiological parameters and visceral
injuries were assessed. Statistical analysis was performed using STATA V.15.0.
RESULTS: A total of 562 patients underwent trauma laparotomy during the period
under review. The mechanism was penetrating trauma in 81% of cases (453/562). A
great proportion of trauma victims were male (503/562, 90%), with a mean age of
29.5+/-10.8. A total of 99 of these (18%) had a DCS procedure versus 463 (82%)
non-DCS. Out of the 99 who required DCS, there were 32 mortalities (32%). The
mean physiological parameters for the DCS patient demonstrated acidosis (pH
7.28+/-0.15) with a raised lactate (5.25 mmol/L+/-3.71). Our primary repair rates
for enteric injuries were surprisingly high. CONCLUSION: Just under 20% of trauma
laparotomies require DCS. In this cohort of patients, the mortality rate is just
under one-third. Further attention must be paid to refining the appropriate
indications for DCS as the margin for error in such a cohort is very small and
poor decision-making is difficult to correct. The major lesson from this analysis
is that the decision to perform DCS must be made early and communicated
appropriately to all those managing the patient.
PMID- 29950300
TI - The Impact of Glycated Hemoglobin (HbA1c) on Cardiovascular Disease Risk: A
Mendelian Randomization Study Using UK Biobank.
AB - OBJECTIVE: Glycated hemoglobin (HbA1c) is positively associated with
cardiovascular disease (CVD), although evidence is primarily observational.
Mendelian randomization studies have only examined its relation with subtypes of
CVD. We examined the relation of HbA1c with CVD and its subtypes in the UK
Biobank using Mendelian randomization. RESEARCH DESIGN AND METHODS: We used 38
genetic variants strongly and independently related to HbA1c (n = 123,665)
applied to the UK Biobank (n = 392,038). We used inverse variance weighting (IVW)
to obtain the associations of HbA1c with CVD, coronary artery disease (CAD), and
stroke (overall and stroke subtypes). Sensitivity analyses included Mendelian
randomization (MR)-Egger, a weighted median, and exclusion of potentially invalid
single nucleotide polymorphisms (SNPs). We also applied the same genetic
instruments to CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication
and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics)
1000 Genomes-based genome-wide association study (n = 184,305) as a validation
for CAD. RESULTS: In the UK Biobank, HbA1c was not associated with CVD using IVW
(odds ratio [OR] 1.11 per %, 95% CI 0.83-1.48). However, HbA1c was associated
with increased CAD risk (OR 1.50 per %, 95% CI 1.08-2.11) with directionally
consistent results from MR-Egger and weighted median. The positive association
with CAD was more pronounced when we excluded potentially invalid SNPs (OR 2.24
per %, 95% CI 1.55-3.25). The positive association was replicated in CARDIoGRAM
(OR 1.52 per %, 95% CI 1.03-2.26). The association of HbA1c with stroke and its
subtypes was less clear given the low number of cases. CONCLUSIONS: HbA1c likely
causes CAD. The underlying mechanisms remain to be elucidated.
PMID- 29950301
TI - 'Corkscrews' on the patchy alopecia of a girl.
PMID- 29950303
TI - The multifaceted roles of the matrikine Pro-Gly-Pro in pulmonary health and
disease.
AB - Matrikines are bioactive fragments of the extracellular matrix (ECM) that are
fundamental in regulating a diverse array of physiological processes. The
tripeptide Proline-Glycine-Proline (PGP) is a collagen-derived matrikine that has
classically been described as a neutrophil chemoattractant. In this article, we
describe our current understanding of the pathways that generate, degrade and
modify PGP to dictate its bioavailability and stability. Additionally, we discuss
our expanding appreciation of the capacity of PGP to regulate diverse cell types
and biological processes, independent of its activity on neutrophils, including a
putative role in wound repair. We argue that PGP functions as a primitive and
conserved damage-associated molecular pattern, which is generated during
infection or injury and subsequently acts to shape ensuing inflammatory and
repair processes. As a fragment of the ECM that accumulates at the epicentre of
the action, PGP is perfectly positioned to focus neutrophils to the exact site
required and direct a localised repair response. However, it is essential that
PGP is efficiently degraded, as if this matrikine is allowed to persist then
pathology can ensue. Accordingly, we discuss how this pathway is subverted in
chronic lung diseases giving rise to persistent inflammation and pathological
tissue remodelling.
PMID- 29950304
TI - How bacteria hack the matrix and dodge the bullets of immunity.
AB - Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa are
common Gram-negative pathogens associated with an array of pulmonary diseases.
All three species have multiple adhesins in their outer membrane, i.e. surface
structures that confer the ability to bind to surrounding cells, proteins or
tissues. This mini-review focuses on proteins with high affinity for the
components of the extracellular matrix such as collagen, laminin, fibronectin and
vitronectin. Adhesins are not structurally related and may be lipoproteins,
transmembrane porins or large protruding trimeric auto-transporters. They enable
bacteria to avoid being cleared together with mucus by attaching to patches of
exposed extracellular matrix, or indirectly adhering to epithelial cells using
matrix proteins as bridging molecules. As more adhesins are being unravelled, it
is apparent that bacterial adhesion is a highly conserved mechanism, and that
most adhesins target the same regions on the proteins of the extracellular
matrix. The surface exposed adhesins are prime targets for new vaccines and the
interactions between proteins are often possible to inhibit with interfering
molecules, e.g heparin. In conclusion, this highly interesting research field of
microbiology has unravelled host-pathogen interactions with high therapeutic
potential.
PMID- 29950305
TI - The consequence of matrix dysfunction on lung immunity and the microbiome in
COPD.
AB - The pulmonary extracellular matrix (ECM) is a complex network of proteins which
primarily defines tissue architecture and regulates various biochemical and
biophysical processes. It is a dynamic system comprising two main structures (the
interstitial matrix and the basement membrane) which undergo continuous, yet
highly regulated, remodelling. This remodelling process is essential for tissue
homeostasis and uncontrolled regulation can lead to pathological states including
chronic obstructive pulmonary disease (COPD). Altered expression of ECM proteins,
as observed in COPD, can contribute to the degradation of alveolar walls and
thickening of the small airways which can cause limitations in airflow.
Modifications in ECM composition can also impact immune cell migration and
retention in the lung with migrating cells becoming entrapped in the diseased
airspaces. Furthermore, ECM changes affect the lung microbiome, aggravating and
advancing disease progression. A dysbiosis in bacterial diversity can lead to
infection, inducing epithelial injury and pro-inflammatory reactions. Here we
review the changes noted in the different ECM components in COPD and discuss how
an imbalance in microbial commensalism can impact disease development.
PMID- 29950302
TI - Detoxication mechanisms of Radix Tripterygium wilfordii via compatibility with
Herba Lysimachia christinae in S180-bearing mice by involving Nrf2.
AB - The combined administration between Radix Tripterygium wilfordii Hook F (LGT) and
Herba Lysimachia christinae Hance (JQC) belongs to mutual detoxication
compatibility of seven emotions in traditional Chinese medicine (TCM) theory.
However, until now, the compatibility detoxication mechanisms remain unknown. The
present study was undertaken to observe detoxication mechanisms of LGT through
compatibility with JQC in tumor-bearing mice by involving NF-E2-related factor 2
(Nrf2)-mediated antioxidant defenses. In addition, influence of compatibility on
antitumor activity was also investigated here. Our results demonstrated that
compatibility with JQC administration significantly reversed LGT-elevated serum
alanine/aspartate transaminase (ALT/AST) levels and alleviated hepatocytes'
swelling or degeneration damage, and at the ratio 2/1 (LGT/JQC) produced the
strongest detoxication effect. Besides, compatibility with JQC administration
reversed not only LGT-elevated hepatic malondialdehyde (MDA) and tumor necrosis
factor-alpha (TNF-alpha) but also the LGT lowered GSH, glutathione-s transferase
(GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT),
and interleukin (IL)-10 levels. Furthermore, compatibility with JQC
administration significantly up-regulated protein expression of Nrf2 and mRNA
expression of it regulated downstream antioxidant genes such as heme oxygenase-1
(HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and glutamate cysteine ligase
catalytic subunit (GCLC). In addition, compatibility with JQC further decreased
LGT-decreased tumor weight and at the ratio 2/1 (LGT/JQC) also exerted the
strongest synergistic effect. Collectively, through compatibility with JQC
exerted detoxication effect on LGT-induced hepatotoxicity and the mechanisms
could be at least partly attributed to up-regulation of Nrf2 and its downstream
signals, thereby enhancing antioxidant defenses, and inhibiting lipid
peroxidation, oxidative stress, and inflammation. Additionally, at the ratio 2/1
(LGT/JQC) exerted the strongest effects on both detoxication and synergism.
PMID- 29950306
TI - Matrix abnormalities in pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a devastating, progressive disease, marked
by excessive scarring, which leads to increased tissue stiffness, loss in lung
function and ultimately death. IPF is characterised by progressive fibroblast and
myofibroblast proliferation, and extensive deposition of extracellular matrix
(ECM). Myofibroblasts play a key role in ECM deposition. Transforming growth
factor (TGF)-beta1 is a major growth factor involved in myofibroblast
differentiation, and the creation of a profibrotic microenvironment. There is a
strong link between increased ECM stiffness and profibrotic changes in cell
phenotype and differentiation. The activation of TGF-beta1 in response to
mechanical stress from a stiff ECM explains some of the influence of the tissue
microenvironment on cell phenotype and function. Understanding the close
relationship between cells and their surrounding microenvironment will ultimately
facilitate better management strategies for IPF.
PMID- 29950307
TI - Cell-matrix interactions in lung disease and regeneration: ERS Lung Science
Conference 2018 report.
PMID- 29950308
TI - Interstitial pneumonia with autoimmune features: a new classification still on
the move.
PMID- 29950309
TI - Newly produced synaptic vesicle proteins are preferentially used in synaptic
transmission.
AB - Aged proteins can become hazardous to cellular function, by accumulating
molecular damage. This implies that cells should preferentially rely on newly
produced ones. We tested this hypothesis in cultured hippocampal neurons,
focusing on synaptic transmission. We found that newly synthesized vesicle
proteins were incorporated in the actively recycling pool of vesicles responsible
for all neurotransmitter release during physiological activity. We observed this
for the calcium sensor Synaptotagmin 1, for the neurotransmitter transporter
VGAT, and for the fusion protein VAMP2 (Synaptobrevin 2). Metabolic labeling of
proteins and visualization by secondary ion mass spectrometry enabled us to query
the entire protein makeup of the actively recycling vesicles, which we found to
be younger than that of non-recycling vesicles. The young vesicle proteins
remained in use for up to ~ 24 h, during which they participated in recycling a
few hundred times. They were afterward reluctant to release and were degraded
after an additional ~ 24-48 h. We suggest that the recycling pool of synaptic
vesicles relies on newly synthesized proteins, while the inactive reserve pool
contains older proteins.
PMID- 29950311
TI - Tiotropium could provide benefits in the early stage of COPD, but further studies
are needed.
PMID- 29950310
TI - Cdc48/p97 segregase is modulated by cyclin-dependent kinase to determine cyclin
fate during G1 progression.
AB - Cells sense myriad signals during G1, and a rapid response to prevent cell cycle
entry is of crucial importance for proper development and adaptation. Cln3, the
most upstream G1 cyclin in budding yeast, is an extremely short-lived protein
subject to ubiquitination and proteasomal degradation. On the other hand, nuclear
accumulation of Cln3 depends on chaperones that are also important for its
degradation. However, how these processes are intertwined to control G1-cyclin
fate is not well understood. Here, we show that Cln3 undergoes a challenging
ubiquitination step required for both degradation and full activation. Segregase
Cdc48/p97 prevents degradation of ubiquitinated Cln3, and concurrently stimulates
its ER release and nuclear accumulation to trigger Start. Cdc48/p97
phosphorylation at conserved Cdk-target sites is important for recruitment of
specific cofactors and, in both yeast and mammalian cells, to attain proper G1
cyclin levels and activity. Cdk-dependent modulation of Cdc48 would subjugate G1
cyclins to fast and reversible state switching, thus arresting cells promptly in
G1 at developmental or environmental checkpoints, but also resuming G1
progression immediately after proliferative signals reappear.
PMID- 29950312
TI - Don't just blame the evidence: considering the role of medical education in the
poor uptake of evidence-based medicine in clinical practice.
PMID- 29950313
TI - Redefining rapid reviews: a flexible framework for restricted systematic reviews.
PMID- 29950314
TI - Variation in analytic transparency in recent efficacy studies of antidepressant
medication.
AB - The validity of clinical trial results is influenced by researchers' decisions
regarding the management of missing data. Inadequate management of missing data
has been identified as a significant source of bias that can result in an
overestimation of drug efficacy. Transparency related to the management of
missing data is essential to assess the strength of evidence reported in
publications. In a subset of 17 randomised clinical trials for two new
antidepressant medications, we present a case study in which we examined
investigators' decisions regarding how to handle missing data and if their chosen
method took into account, possible violations of analytic requirements that could
affect results. The majority of trials (76%) concluded that there was a benefit
of antidepressant treatment and in 94% the methodology for handling missing data
was identifiable. Of these, 50% imputed data using the last observation carried
forward and half used a mixed-effects model repeated measure approach. Most
reports did not provide a rationale for the method used, and no trials described
analyses regarding differences between completers and dropouts. Sensitivity
analysis was inconsistently reported and correction for multiple comparisons was
not uniformly applied. Lack of transparency for analytic choices related to
handling of missing data testing was common in this subset of RCTs. Because
management of missing data can directly influence the quality of study results,
it is critical that journal editors develop and enforce standards for
methodological transparency.
PMID- 29950315
TI - Disrupting LXRalpha phosphorylation promotes FoxM1 expression and modulates
atherosclerosis by inducing macrophage proliferation.
AB - Macrophages are key immune cells for the initiation and development of
atherosclerotic lesions. However, the macrophage regulatory nodes that determine
how lesions progress in response to dietary challenges are not fully understood.
Liver X receptors (LXRs) are sterol-regulated transcription factors that play a
central role in atherosclerosis by integrating cholesterol homeostasis and
immunity. LXR pharmacological activation elicits a robust antiatherosclerotic
transcriptional program in macrophages that can be affected by LXRalpha S196
phosphorylation in vitro. To investigate the impact of these transcriptional
changes in atherosclerosis development, we have generated mice carrying a Ser-to
Ala mutation in myeloid cells in the LDL receptor (LDLR)-deficient
atherosclerotic background (M-S196ALdlr-KO). M-S196ALdlr-KO mice fed a high-fat
diet exhibit increased atherosclerotic plaque burden and lesions with smaller
necrotic cores and thinner fibrous caps. These diet-induced phenotypic changes
are consistent with a reprogramed macrophage transcriptome promoted by LXRalpha
S196A during atherosclerosis development. Remarkably, expression of several
proliferation-promoting factors, including the protooncogene FoxM1 and its
targets, is induced by LXRalpha-S196A. This is consistent with increased
proliferation of plaque-resident cells in M-S196ALdlr-KO mice. Moreover,
disrupted LXRalpha phosphorylation increases expression of phagocytic molecules,
resulting in increased apoptotic cell removal by macrophages, explaining the
reduced necrotic cores. Finally, the macrophage transcriptome promoted by
LXRalpha-S196A under dietary perturbation is markedly distinct from that revealed
by LXR ligand activation, highlighting the singularity of this posttranslational
modification. Overall, our findings demonstrate that LXRalpha phosphorylation at
S196 is an important determinant of atherosclerotic plaque development through
selective changes in gene transcription that affect multiple pathways.
PMID- 29950316
TI - Dissecting the neurofunctional bases of intentional action.
AB - Here we challenge and present evidence that expands the what, when, and whether
anatomical model of intentional action, which states that internally driven
decisions about the content and timing of our actions and about whether to act at
all depend on separable neural systems, anatomically segregated along the medial
wall of the frontal lobe. In our fMRI event-related paradigm, subjects acted
following conditional cues or following their intentions. The content of the
actions, their timing, or their very occurrence were the variables investigated,
together with the modulating factor of intentionality. Besides a shared
activation of the pre-supplementary motor area (pre-SMA) and anterior cingulate
cortex (ACC) for all components and the SMA proper for the when component, we
found specific activations beyond the mesial prefrontal wall involving the
parietal cortex for the what component or subcortical gray structures for the
when component. Moreover, we found behavioral, functional, anatomical, and brain
connectivity evidence that the self-driven decisions on whether to act require a
higher interhemispheric cooperation: This was indexed by a specific activation of
the corpus callosum whereby the less the callosal activation, the greater was the
decision cost at the time of the action in the whether trials. Furthermore,
tractography confirmed that the fibers passing through the callosal focus of
activation connect the two sides of the frontal lobes involved in intentional
trials. This is evidence of non-unitary neural foundations for the processes
involved in intentional actions with the pre-SMA/ACC operating as an intentional
hub. These findings may guide the exploration of specific instances of disturbed
intentionality.
PMID- 29950317
TI - Ecological specialization, variability in activity patterns and response to
environmental change.
AB - Differences in temporal patterns of activity can modulate the ambient conditions
to which organisms are exposed, providing an important mechanism for responding
to environmental change. Such differences may be particularly relevant to
ecological generalists, which are expected to encounter a wider range of
environmental conditions. Here, we compare temporal patterns of activity for
partially sympatric populations of a generalist (the lodgepole chipmunk, Tamias
speciosus) and a more specialized congener (the alpine chipmunk, Tamias alpinus)
that have displayed divergent responses to the past century of environmental
change. Although mean activity budgets were similar between species, analyses of
individual-level variation in locomotion revealed that T. alpinus exhibited a
narrower range of activity patterns than Tspeciosus Further analyses revealed
that T. alpinus was more active earlier in the day, when temperatures were
cooler, and that activity patterns for both species changed with increased
interspecific co-occurrence. These results are consistent with the greater
responsiveness of T. alpinus to changes in environmental conditions. In addition
to highlighting the utility of accelerometers for collecting behavioural data,
our findings add to a growing body of evidence, suggesting that the greater
phenotypic variability displayed by ecological generalists may be critical to in
situ responses to environmental change.
PMID- 29950318
TI - Histology of the endothermic opah (Lampris sp.) suggests a new structure-function
relationship in teleost fish bone.
AB - Endothermy, production and retention of heat by the body, appeared convergently
in mammals, birds and four spiny-rayed teleost fish lineages. Of these, red
muscle endothermy over most or all of the body has only appeared in two groups:
tunas and the opah (Lampris). Hitherto, tunas have been the only spiny-rayed
fishes known to have bones containing embedded osteocyte cells; others have
acellular bone. We examined bone histology in Lampris for the first time,
demonstrating the presence of cellular bone very similar to that of tunas. This
contrasts with the acellular condition of its ectothermic close relatives. The
distribution of this character suggests that it co-evolved with red-muscle
endothermy, hinting at a common physiological mechanism that would link bone
histology to endothermy in these distantly related teleost lineages.
PMID- 29950319
TI - Advancing genomic approaches to the molecular diagnosis of mitochondrial disease.
AB - Mitochondrial diseases present a diagnostic challenge due to their clinical and
genetic heterogeneity. Achieving comprehensive molecular diagnosis via a
conventional candidate-gene approach is likely, therefore, to be labour- and cost
intensive given the expanding number of mitochondrial disease genes. The advent
of whole exome sequencing (WES) and whole genome sequencing (WGS) hold the
potential of higher diagnostic yields due to the universality and unbiased nature
of the methods. However, these approaches are subject to the escalating challenge
of variant interpretation. Thus, integration of functional 'multi-omics' data,
such as transcriptomics, is emerging as a powerful complementary tool in the
diagnosis of mitochondrial disease patients for whom extensive prior analysis of
DNA sequencing has failed to return a genetic diagnosis.
PMID- 29950321
TI - Mitochondrial DNA replication: clinical syndromes.
AB - Each nucleated cell contains several hundreds of mitochondria, which are unique
organelles in being under dual genome control. The mitochondria contain their own
DNA, the mtDNA, but most of mitochondrial proteins are encoded by nuclear genes,
including all the proteins required for replication, transcription, and repair of
mtDNA. MtDNA replication is a continuous process that requires coordinated action
of several enzymes that are part of the mtDNA replisome. It also requires
constant supply of deoxyribonucleotide triphosphates(dNTPs) and interaction with
other mitochondria for mixing and unifying the mitochondrial compartment. MtDNA
maintenance defects are a growing list of disorders caused by defects in nuclear
genes involved in different aspects of mtDNA replication. As a result of defects
in these genes, mtDNA depletion and/or multiple mtDNA deletions develop in
affected tissues resulting in variable manifestations that range from adult-onset
mild disease to lethal presentation early in life.
PMID- 29950322
TI - FDA approves its first cannabis based medicine.
PMID- 29950320
TI - Advances in methods for reducing mitochondrial DNA disease by replacing or
manipulating the mitochondrial genome.
AB - Mitochondrial DNA (mtDNA) is a multi-copy genome whose cell copy number varies
depending on tissue type. Mutations in mtDNA can cause a wide spectrum of
diseases. Mutated mtDNA is often found as a subset of the total mtDNA population
in a cell or tissue, a situation known as heteroplasmy. As mitochondrial
dysfunction only presents after a certain level of heteroplasmy has been
acquired, ways to artificially reduce or replace the mutated species have been
attempted. This review addresses recent approaches and advances in this field,
focusing on the prevention of pathogenic mtDNA transfer via mitochondrial
donation techniques such as maternal spindle transfer and pronuclear transfer in
which mutated mtDNA in the oocyte or fertilized embryo is substituted with normal
copies of the mitochondrial genome. This review also discusses the molecular
targeting and cleavage of pathogenic mtDNA to shift heteroplasmy using
antigenomic therapy and genome engineering techniques including Zinc-finger
nucleases and transcription activator-like effector nucleases. Finally, it
considers CRISPR technology and the unique difficulties that mitochondrial genome
editing presents.
PMID- 29950323
TI - Developing a hospital-wide quality and safety dashboard: a qualitative research
study.
AB - BACKGROUND: Several countries have national policies and programmes requiring
hospitals to use quality and safety (QS) indicators. To present an overview of
these indicators, hospital-wide QS (HWQS) dashboards are designed. There is
little evidence how these dashboards are developed. The challenges faced to
develop these dashboards in Dutch hospitals were retrospectively studied.
METHODS: 24 focus group interviews were conducted: 12 with hospital managers
(n=25; 39.7%) and 12 support staff (n=38; 60.3%) in 12 of the largest Dutch
hospitals. Open and axial codings were applied consecutively to analyse the data
collected. RESULTS: A heuristic tool for the general development process for HWQS
dashboards containing five phases was identified. In phase 1, hospitals make
inventories to determine the available data and focus too much on quantitative
data relevant for accountability. In phase 2, hospitals develop dashboard content
by translating data into meaningful indicators for different users, which is not
easy due to differing demands. In phase 3, hospitals search for layouts that
depict the dashboard content suited for users with different cognitive abilities
and analytical skills. In phase 4, hospitals try to integrate dashboards into
organisational structures to ensure that data are systematically reviewed and
acted on. In phase 5, hospitals want to improve the flexibility of their
dashboards to make this adaptable under differing circumstances. CONCLUSION: The
literature on dashboards addresses the technical and content aspects of
dashboards, but overlooks the organisational development process. This study
shows how technical and organisational aspects are relevant in development
processes.
PMID- 29950325
TI - Response to: 'Infrapatellar fat pad resection during total knee replacement: yet
another reason?' by Ryan.
PMID- 29950324
TI - Implementing infection prevention practices across European hospitals: an in
depth qualitative assessment.
AB - OBJECTIVE: The Prevention of Hospital Infections by Intervention and Training
(PROHIBIT) project included a cluster-randomised, stepped wedge, controlled study
to evaluate multiple strategies to prevent catheter-related bloodstream
infection. We report an in-depth investigation of the main barriers, facilitators
and contextual factors relevant to successfully implementing these strategies in
European acute care hospitals. METHODS: Qualitative comparative case study in 6
of the 14 European PROHIBIT hospitals. Data were collected through interviews
with key stakeholders and ethnographic observations conducted during 2-day site
visits, before and 1 year into the PROHIBIT intervention. Qualitative measures of
implementation success included intervention fidelity, adaptation to local
context and satisfaction with the intervention programme. RESULTS: Three meta
themes emerged related to implementation success: 'implementation agendas',
'resources' and 'boundary-spanning'. Hospitals established unique implementation
agendas that, while not always aligned with the project goals, shaped subsequent
actions. Successful implementation required having sufficient human and material
resources and dedicated change agents who helped make the intervention an
institutional priority. The salary provided for a dedicated study nurse was a key
facilitator. Personal commitment of influential individuals and boundary spanners
helped overcome resource restrictions and intrainstitutional segregation.
CONCLUSION: This qualitative study revealed patterns across cases that were
associated with successful implementation. Consideration of the intervention
context relation was indispensable to understanding the observed outcomes.
PMID- 29950326
TI - Checkpoint inhibitors and arthritis: seeking balance between victories and
defeats.
PMID- 29950327
TI - Trimethoprim-sulfamethoxazole prophylaxis prevents severe/life-threatening
infections following rituximab in antineutrophil cytoplasm antibody-associated
vasculitis.
AB - OBJECTIVE: We aimed to assess risk factors for the development of severe
infection in patients with antineutrophil cytoplasm antibody-associated
vasculitis (AAV) receiving rituximab. METHODS: 192 patients with AAV were
identified. Univariate and multivariate analyses were performed to identify risk
factors for severe infection following rituximab. Severe infections were
classified as grade >=3 as proposed by the Common Terminology Criteria for
Adverse Events V.4.0. RESULTS: 95 severe infections were recorded in 49 (25.52%)
patients, corresponding to an event rate of 26.06 per 100 person-years. The
prophylactic use of trimethoprim-sulfamethoxazole was associated with a lower
frequency of severe infections (HR 0.30, 95% CI 0.13 to 0.69), while older age
(HR 1.03, 95% CI 1.01 to 1.05), endobronchial involvement (HR 2.21, 95% CI 1.14
to 4.26), presence of chronic obstructive pulmonary disease (HR 6.30, 95% CI 1.08
to 36.75) and previous alemtuzumab use (HR 3.97, 95% CI 1.50 to 10.54) increased
the risk. When analysis was restricted to respiratory tract infections (66.3% of
all infections), endobronchial involvement (HR 4.27, 95% CI 1.81 to 10.06),
severe bronchiectasis (HR 6.14, 95% CI 1.18 to 31.91), higher neutrophil count
(HR 1.19, 95% CI 1.06 to 1.33) and major relapse (HR 3.07, 95% CI 1.30 to 7.23)
as indication for rituximab use conferred a higher risk, while refractory disease
(HR 0.25, 95% CI 0.07 to 0.90) as indication had a lower frequency of severe
infections. CONCLUSIONS: We found severe infections in one quarter of patients
with AAV receiving rituximab. Trimethoprim-sulfamethoxazole prophylaxis reduced
the risk, while especially bronchiectasis and endobronchial involvement are risk
factors for severe respiratory infections.
PMID- 29950328
TI - Lowering the Barriers to Routine Whole-Genome Sequencing of Bacteria in the
Clinical Microbiology Laboratory.
AB - Whole-genome sequencing of bacterial isolates is increasingly being used to
predict antibacterial susceptibility and resistance. Mason and coauthors describe
the phenotypic susceptibility interpretations of more than 1,300 Staphylococcus
aureus isolates tested against a dozen antistaphylococcal agents, and they
compared these findings to susceptibility predictions made by analyzing whole
genome sequence data (J Clin Microbiol 56:e01815-17, 2018,
https://doi.org/10.1128/JCM.01815-17). The genotype-phenotype susceptibility
interpretations correlated in 96.3% (2,720/2,825) of resistant findings and 98.8%
(11,504/11,639) of susceptible findings. This work by Mason and colleagues is
helping to lower the barriers to using whole-genome sequencing of S. aureus in
clinical microbiology practice.
PMID- 29950329
TI - Rapid Detection of Candida auris Based on Loop-Mediated Isothermal Amplification
(LAMP).
PMID- 29950330
TI - Mycobacterium bovis Persistence in Two Different Captive Wild Animal Populations
in Germany: a Longitudinal Molecular Epidemiological Study Revealing Pathogen
Transmission by Whole-Genome Sequencing.
AB - Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a transmissible
disease notifiable to the World Organization for Animal Health and to the
European Union, with ongoing efforts of surveillance and eradication in every EU
member state. In Germany, a country which has been declared officially free from
bovine tuberculosis since 1997 by the EU, M. bovis infections still occur
sporadically in cattle and other mammals, including humans. Here, the
transmission routes of a bTB outbreak in a wildlife park in Germany affecting
different cervid species, bison, lynx, and pot-bellied pigs were followed by
employing whole-genome sequencing (WGS) combined with spoligotyping and
mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU
VNTR) typing. One single M. bovis strain persisted from 2002 to 2015, and
transmission between the park and a distantly located captive cervid farm was
verified. The spoligotyping patterns remained identical, while MIRU-VNTR typing
of 24 loci of the standardized panel and locus 2163a as an additional locus
revealed one change at locus 2165 in a strain from a fallow deer and one at locus
2461 in isolates from red deer over the whole time period. WGS analysis confirmed
the close relatedness of the isolates, with a maximum of 12 single nucleotide
polymorphisms (SNPs) detected between any two sequenced isolates. In conclusion,
our data confirm a longitudinal outbreak of M. bovis in a German wildlife park
and provide the first insights into the dynamics of different genotyping markers
in M. bovis.
PMID- 29950331
TI - Ornithodoros savignyi, the Tick Vector of "Candidatus Borrelia kalaharica" in
Nigeria.
AB - Endemic tick-borne relapsing fever (TBRF) has not been documented in Nigeria, yet
clinically compatible cases have been described, and soft tick species are
endemic in surrounding countries. Consequently, our aim was to investigate if
TBRF-associated Borrelia is present in Nigeria. To address this, we examined 49
soft tick pools to identify the tick species and to screen for Borrelia The tick
species was revealed by 16S rRNA gene amplification and Sanger sequencing to be
Ornithodoros savignyi, an aggressive, multihost, rapidly feeding species with
significant veterinary impact. We detected a Borrelia organism in 3 of 49 pooled
samples (6%). Molecular analysis of amplified 16S rRNA and flagellin genes and
intragenic spacer fragments disclosed that this Borrelia organism was synonymous
with the recently described organism "Candidatus Borrelia kalaharica," identified
in a tourist returning to Germany from South Africa. Given the widespread endemic
range of this tick vector, TBRF should be considered part of the differential
diagnosis for patients with fever returning from arid areas of Africa and further
afield.
PMID- 29950332
TI - Modified Protein Misfolding Cyclic Amplification Overcomes Real-Time Quaking
Induced Conversion Assay Inhibitors in Deer Saliva To Detect Chronic Wasting
Disease Prions.
AB - Chronic wasting disease (CWD), a fatal neurodegenerative prion disease of
cervids, has spread across North America and has been detected in The Republic of
Korea, Finland, and Norway. CWD appears to spread by horizontal transmission, and
prions shed in saliva, feces, and urine are thought to contribute. However,
studies investigating the rapid spread of CWD have been hampered by assay
inhibitors and a lack of consistent and sensitive means to detect the relatively
low levels of prions in these samples. Here we show that saliva frequently
contains an inhibitor of the real-time quaking-induced conversion assay (RT-QuIC)
and that the inhibitor is a member of the mucin family. To circumvent the
inhibitor, we developed a modified protein misfolding cyclic amplification (PMCA)
method to amplify CWD prions in saliva that were undetectable or ambiguous by RT
QuIC. Our results reinforce the impact of saliva in horizontal CWD transmission
and highlight the importance of detection optimization.
PMID- 29950333
TI - Evaluation of the Xpert MTB/RIF Ultra Assay for Direct Detection of Mycobacterium
tuberculosis Complex in Smear-Negative Extrapulmonary Samples.
AB - The rapid detection of Mycobacterium tuberculosis complex (MTUBC) in clinical
samples is essential for successful treatment. New techniques such as real-time
PCR have been developed in order to facilitate rapid diagnosis, but their
sensitivity is low in extrapulmonary specimens, due to the low bacillary load in
such samples. A next-generation assay has recently been developed to try to
overcome this limitation. The aim of this study was to analyze the effectiveness
of the Xpert MTB/RIF Ultra (GX-Ultra) for the detection of MTUBC DNA in 108 smear
negative extrapulmonary specimens that were MTUBC culture positive. In addition,
40 extrapulmonary culture-negative samples and 20 samples with nontuberculous
mycobacteria were tested to evaluate the specificity of the assay. All samples
were collected between May 1999 and May 2017. The GX-Ultra detected DNA of MTUBC
in 82 extrapulmonary specimens that were MTUBC culture positive (75.9%
sensitivity; 95% confidence interval [CI], 66.6 to 83.4%). The assay was negative
for all clinical specimens that were MTUBC culture negative and the samples with
nontuberculous mycobacteria (100% specificity). Furthermore, two (1.8%) samples
presented mutations related to rifampin resistance. The highest sensitivity was
obtained in samples of lymph nodes (94.1%) and nonsterile fluids (93.7%),
followed by tissue specimens (86.6%), stool material (80%), abscess aspirates
(64.7%), and sterile fluids (60.5%). Pleural fluids, one of the least optimal
samples for detecting DNA of MTUBC, were GX-Ultra positive in 10/21 (47.6%) of
cases. In summary, GX-Ultra showed excellent specificity and high sensitivity in
paubacillary specimens, making it a useful tool for rapid diagnosis of
extrapulmonary tuberculosis.
PMID- 29950334
TI - Phase Variation of NadA in Invasive Neisseria meningitidis Isolates Impacts on
Coverage Estimates for 4C-MenB, a MenB Vaccine.
AB - A recombinant NadA protein is one of the four major protective antigens of 4C
MenB (Bexsero), a vaccine developed for serogroup B Neisseria meningitidis
(MenB). The meningococcal antigen typing system (MATS) is utilized as a high
throughput assay for assessing the invasive MenB strain coverage of 4C-MenB.
Where present, the nadA gene is subject to phase-variable changes in
transcription due to a 5'TAAA repeat tract located in a regulatory region. The
promoter-containing intergenic region (IGR) sequences and 5'TAAA repeat numbers
were determined for 906 invasive meningococcal disease isolates possessing the
nadA gene. Exclusion of the 5'TAAA repeats reduced the number of IGR alleles from
82 to 23. Repeat numbers were associated with low and high levels of NadA
expression by Western blotting and enzyme-linked immunosorbent assay (ELISA). Low
expression repeat numbers were present in 83% of 179 MenB isolates with NadA-2/3
or NadA-1 peptide variants and 68% of 480 MenW ST-11 complex isolates with NadA
2/3 peptide variants. For isolates with vaccine-compatible NadA variants, 93% of
MATS-negative isolates were associated with low-expression repeat numbers,
whereas 63% of isolates with MATS relative potency (RP) scores above the 95%
confidence interval for the positive bactericidal threshold had high-expression
repeat numbers. Analysis of 5'TAAA repeat numbers has potential as a rapid, high
throughput method for assessing strain coverage for the NadA component of 4C
MenB. A key application will be assessing coverage in meningococcal disease cases
where confirmation is by PCR only and MATS cannot be applied.
PMID- 29950335
TI - Viability of Candida auris and Other Candida Species after Various Matrix
Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) Mass Spectrometry
Based Extraction Protocols.
PMID- 29950336
TI - Within-a-Day Detection and Rapid Characterization of Carbapenemase by Use of a
New Carbapenem Inactivation Method-Based Test, CIMplus.
AB - The dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a major
threat to public health. Rapid and accurate detection of CPE is essential for
initiating appropriate antimicrobial treatment and establishing infection control
measures. The carbapenem inactivation method (CIM), which has good sensitivity
and specificity but a detection time of 20 h, was recently described. In this
study, we evaluated the performances of a new version, the CIMplus test, which
allows detection of carbapenemases in 8 h and characterization of carbapenemase
classes, according to the Ambler classification, in 20 h. A panel of 110
carbapenem-resistant Enterobacteriaceae strains, including 92 CPE strains (with
NDM, VIM, IMP, KPC, GES, OXA-48, and OXA-48-like enzymes), was used to evaluate
test performance. Carbapenemase activity was detected at 8 h and 20 h.
Characterization of carbapenemase classes, using specific inhibitors, was
possible in 20 h. The CIMplus test had sensitivities of 95.7% and 97.8% at 8 h
and 20 h, respectively, and a specificity of 94.4%, independent of the culture
duration. Using a decision algorithm, this test was successful in identifying the
carbapenemase class for 98.9% of tested CPE isolates (87/88 isolates). In total,
the characterization was correct for 100%, 96.9%, and 100% of Ambler class A, B,
and D isolates, respectively. Therefore, this test allows detection of
carbapenemase activity in 8 h and characterization of carbapenemase classes,
according to the Ambler classification, in 20 h. The CIMplus test represents a
simple, affordable, easy-to-read, and accurate tool that can be used without any
specific equipment.
PMID- 29950337
TI - Hypervirulent Klebsiella pneumoniae: a Call for Consensus Definition and
International Collaboration.
AB - Hypervirulent Klebsiella pneumoniae strains have higher potential to cause more
severe and disseminated infections than classic K. pneumoniae strains. While
initially reported from East Asian countries, cases have now been identified
worldwide, sometimes in conjunction with extensive drug resistance. In this issue
of the Journal of Clinical Microbiology, T. A. Russo et al. (J Clin Microbiol
56:e00776-18, 2018, https://doi.org/10.1128/JCM.00776-18) validated the
diagnostic accuracy of biomarkers that differentiate hypervirulent K. pneumoniae
strains from classic strains. This represents a major step forward in building a
consensus definition and designing international studies aimed at elucidating the
global epidemiology, clinical features, and outcome of this important pathogen.
PMID- 29950338
TI - Rapid Detection of Carbapenemase Production Directly from Blood Culture by
Colorimetric Methods: Evaluation in a Routine Microbiology Laboratory.
AB - The aim of this study was to evaluate the two rapid colorimetric methods (CNPt
Direct and Blue-Carba) for the detection of carbapenemase production directly
from blood culture in a routine microbiology laboratory. The methods were
initially evaluated on spiked blood cultures with 61 carbapenemase-positive
isolates. Afterwards, they were used in blood cultures (314 samples were
evaluated) obtained from patients in a routine microbiology laboratory during a
period of 6 months. The colorimetric methods were compared to the conventional
culture of blood. The results of the spiked blood cultures indicated that both
colorimetric methods presented positive results for the vast majority (95%) of
the isolates harboring KPC, NDM, and IMP genes. However, the assay failed to
detect many GES- and OXA-48-like-positive isolates (65% positive results). In the
second part of the study, a total of 314 blood cultures from patients were
evaluated, and 33 yielded Enterobacteriaceae isolates resistant to meropenem (30
isolates were positive for carbapenemases according to PCR). The colorimetric
tests correctly detected 24 out of the 30 carbapenemase-positive isolates
directly from the blood vial (80% positive results). Overall positive percent
agreement and negative percent agreement were 80% and 100%, respectively. The
colorimetric assays are simple and cost-effective methods that can be implemented
in a routine microbiology laboratory, diminishing the time necessary to detect
carbapenemase-producing isolates from 24 to 48 h to 3 to 5 h. Moreover, according
to our results, the positive colorimetric test results do not need to be
confirmed and can be immediately provided to the attending physician.
PMID- 29950339
TI - Mismatch Amplification Mutation Assay-Based Real-Time PCR for Rapid Detection of
Neisseria gonorrhoeae and Antimicrobial Resistance Determinants in Clinical
Specimens.
AB - Molecular methods are often used for Neisseria gonorrhoeae detection, but
complete definition of antimicrobial resistance (AMR) patterns still requires
phenotypic tests. We developed an assay that both identifies N. gonorrhoeae and
detects AMR determinants in clinical specimens. We designed a mismatch
amplification mutation assay (MAMA)-based SYBR green real-time PCR targeting one
N. gonorrhoeae-specific region (opa); mosaic penA alleles (Asp345 deletion
[Asp345del], Gly545Ser) associated with decreased susceptibility to
cephalosporins; and alterations conferring resistance to ciprofloxacin (GyrA
Ser91Phe), azithromycin (23S rRNA A2059G and C2611T), and spectinomycin (16S rRNA
C1192T). We applied the real-time PCR to 489 clinical specimens, of which 94 had
paired culture isolates, and evaluated its performance by comparison with the
performance of commercial diagnostic molecular and phenotypic tests. Our assay
exhibited a sensitivity/specificity of 93%/100%, 96%/85%, 90%/91%, 100%/100%, and
100%/90% for the detection of N. gonorrhoeae directly from urethral, rectal,
pharyngeal, cervical, and vaginal samples, respectively. The MAMA strategy
allowed the detection of AMR mutations by comparing cycle threshold values with
the results of the reference opa reaction. The method accurately predicted the
phenotype of resistance to four antibiotic classes, as determined by comparison
with the MIC values obtained from 94 paired cultures (sensitivity/specificity for
cephalosporins, azithromycin, ciprofloxacin, and spectinomycin resistance,
100%/95%, 100%/100%, 100%/100%, and not applicable [NA]/100%, respectively, in
genital specimens and NA/72%, NA/98%, 100%/97%, and NA/96%, respectively, in
extragenital specimens). False-positive results, particularly for the penA
Asp345del reaction, were observed predominantly in pharyngeal specimens. Our real
time PCR assay is a promising rapid method to identify N. gonorrhoeae and predict
AMR directly in genital specimens, but further optimization for extragenital
specimens is needed.
PMID- 29950340
TI - Identity, environment and mental wellbeing in the veterinary profession.
AB - Mental health and career dissatisfaction are of increasing concern to the
veterinary profession. The influence of identity on the psychological wellbeing
of veterinarians has not been widely explored. Twelve recent veterinary graduates
were enrolled in a private social media discussion group, and their identities
investigated through narrative inquiry: a methodology which enables identity
priorities to be extrapolated from stories of experience. Two distinct variants
of the veterinary identity were identified: an academic, 'diagnosis-focused'
identity, which prioritised definitive diagnosis and best-evidence treatment; and
a broader 'challenge-focused' identity, where priorities additionally included
engaging with the client, challenging environment or veterinary business.
Contextual challenges (such as a client with limited finances or difficult
interpersonal interactions) were seen as a source of frustration for those with a
diagnosis-focused identity, as they obstructed the realisation of identity goals.
Overcoming these challenges provided satisfaction to those with a challenge
focused identity. The employment environment of the graduates (general veterinary
practice) provided more opportunities for those with a challenge-focused identity
to realise identity goals, and more markers of emotional wellbeing were apparent
in their stories. Markers of poor emotional health were evident in the stories of
those with a diagnosis-focused identity.
PMID- 29950341
TI - Multiresistant Brachyspira hyodysenteriae shedding by pigs during the fattening
period.
PMID- 29950342
TI - End of life decisions-the patient comes first.
PMID- 29950344
TI - Impact of characteristics of organ failure and infected necrosis on mortality in
necrotising pancreatitis.
AB - OBJECTIVE: In patients with pancreatitis, early persisting organ failure is
believed to be the most important cause of mortality. This study investigates the
relation between the timing (onset and duration) of organ failure and mortality
and its association with infected pancreatic necrosis in patients with
necrotising pancreatitis. DESIGN: We performed a post hoc analysis of a
prospective database of 639 patients with necrotising pancreatitis from 21
hospitals. We evaluated the onset, duration and type of organ failure (ie,
respiratory, cardiovascular and renal failure) and its association with mortality
and infected pancreatic necrosis. RESULTS: In total, 240 of 639 (38%) patients
with necrotising pancreatitis developed organ failure. Persistent organ failure
(ie, any type or combination) started in the first week in 51% of patients with
42% mortality, in 13% during the second week with 46% mortality and in 36% after
the second week with 29% mortality. Mortality in patients with persistent
multiple organ failure lasting <1 week, 1-2 weeks, 2-3 weeks or longer than 3
weeks was 43%, 38%, 46% and 52%, respectively (p=0.68). Mortality was higher in
patients with organ failure alone than in patients with organ failure and
infected pancreatic necrosis (44% vs 29%, p=0.04). However, when excluding
patients with very early mortality (within 10 days of admission), patients with
organ failure with or without infected pancreatic necrosis had similar mortality
rates (28% vs 34%, p=0.33). CONCLUSION: In patients with necrotising
pancreatitis, early persistent organ failure is not associated with increased
mortality when compared with persistent organ failure which develops further on
during the disease course. Furthermore, no association was found between the
duration of organ failure and mortality.
PMID- 29950345
TI - Trastuzumab Deruxtecan Targets HER2+ Cancers.
AB - The antibody-drug conjugate trastuzumab deruxtecan may be an effective treatment
for patients with HER2-positive cancers whose disease has progressed despite the
use of other therapies. In a phase I trial, patients treated with the drug had
high overall response rates and rates of tumor shrinkage, but many also
experienced serious gastrointestinal and hematologic side effects.
PMID- 29950346
TI - Erdafitinib Efficacious in Bladder Cancer.
AB - Findings from a phase II study indicate clinical efficacy with erdafitinib in
patients with FGFR-altered inoperable or metastatic urothelial carcinoma. Robust
responses were seen with this investigational pan-FGFR inhibitor, including in
patients who did not respond to prior immunotherapy.
PMID- 29950343
TI - Adipocytes and intestinal epithelium dysfunctions linking obesity to inflammation
induced by high glycemic index pellet-diet in Wistar rats.
AB - We investigated the inflammatory effect of a pellet-diet with high glycemic index
and load (HGLI) on the histological organization of adipocytes, intestinal
epithelium, and fat in liver and pancreas in adult male Wistar rats. Two groups
(n=10) received for 17 weeks: (1) HGLI diet or (2) Standard diet (Labina(r)).
Histological analyses of adipose tissue, jejunum, liver, and pancreas were
performed. Stereology analysis, visceral adiposity index, gene expression, and
immunohistochemistry of tumor necrosis factor-alpha (TNF-alpha) in visceral
adipose tissue and plasma TNF-alpha were also assessed. The HGLI diet-induced
hypertrophy of adipocytes with adipocyte volume density equal to 97.0%, cross
sectional area of adipocytes equivalent to 1387 um2 and a total volume of
adipocytes of 6.97 cm3 an elevation of 8%, 25%, and 58%, respectively.
Furthermore, the HGLI diet increased liver and pancreatic fat deposition, altered
and inflamed the intestinal epithelia, and increased TNF-alpha gene expression
(P=0.014) with a positive immunostaining in visceral adipose tissue and high
plasma TNF-alpha in comparison with standard diet. The results suggest that this
diet was able to generate changes commonly caused to solid diets with high fat or
fructose-rich beverages. To the best of our knowledge, this is the first report
in the literature concerning the properties of low-cost, sucrose-rich pellet-diet
presenting high glycemic index and high glycemic load efficient on the
development of obesity complications in Wistar rats that were subjected to diet
induced obesity. Therefore, the HGLI pellet-diet may be considered an effective
tool to be used by the scientific community in experimental research.
PMID- 29950347
TI - Quantitative Proteomic Analysis Identifies AHNAK (Neuroblast Differentiation
associated Protein AHNAK) as a Novel Candidate Biomarker for Bladder Urothelial
Carcinoma Diagnosis by Liquid-based Cytology.
AB - Cytological examination of urine is the most widely used noninvasive pathologic
screen for bladder urothelial carcinoma (BLCA); however, inadequate diagnostic
accuracy remains a major challenge. We performed mass spectrometry-based
proteomic analysis of urine samples of ten patients with BLCA and ten paired
patients with benign urothelial lesion (BUL) to identify ancillary proteomic
markers for use in liquid-based cytology (LBC). A total of 4,839 proteins were
identified and 112 proteins were confirmed as expressed at significantly
different levels between the two groups. We also performed an independent
proteomic profiling of tumor tissue samples where we identified 7,916 proteins of
which 758 were differentially expressed. Cross-platform comparisons of these data
with comparative mRNA expression profiles from The Cancer Genome Atlas identified
four putative candidate proteins, AHNAK, EPPK1, MYH14 and OLFM4. To determine
their immunocytochemical expression levels in LBC, we examined protein expression
data from The Human Protein Atlas and in-house FFPE samples. We further
investigated the expression of the four candidate proteins in urine cytology
samples from two independent validation cohorts. These analyses revealed AHNAK as
a unique intracellular protein differing in immunohistochemical expression and
subcellular localization between tumor and non-tumor cells. In conclusion, this
study identified a new biomarker, AHNAK, applicable to discrimination between
BLCA and BUL by LBC. To our knowledge, the present study provides the first
identification of a clinical biomarker for LBC based on in-depth proteomics.
PMID- 29950348
TI - Mutational Analysis Identifies Therapeutic Biomarkers in Inflammatory Bowel
Disease-Associated Colorectal Cancers.
AB - Purpose: Inflammatory bowel disease-associated colorectal cancers (IBD-CRC) are
associated with a higher mortality than sporadic colorectal cancers. The poorly
defined molecular pathogenesis of IBD-CRCs limits development of effective
prevention, detection, and treatment strategies. We aimed to identify biomarkers
using whole-exome sequencing of IBD-CRCs to guide individualized
management.Experimental Design: Whole-exome sequencing was performed on 34
formalin-fixed paraffin-embedded primary IBD-CRCs and 31 matched normal lymph
nodes. Computational methods were used to identify somatic point mutations, small
insertions and deletions, mutational signatures, and somatic copy number
alterations. Mismatch repair status was examined.Results: Hypermutation was
observed in 27% of IBD-CRCs. All hypermutated cancers were from the proximal
colon; all but one of the cancers with hypermutation had defective mismatch
repair or somatic mutations in the proofreading domain of DNA POLE Hypermutated
IBD-CRCs had increased numbers of predicted neo-epitopes, which could be
exploited using immunotherapy. We identified six distinct mutation signatures in
IBD-CRCs, three of which corresponded to known mechanisms of mutagenesis. Driver
genes were also identified.Conclusions: IBD-CRCs should be evaluated for
hypermutation and defective mismatch repair to identify patients with a higher
neo-epitope load who may benefit from immunotherapies. Prospective trials are
required to determine whether IHC to detect loss of MLH1 expression in dysplastic
colonic tissue could identify patients at increased risk of developing IBD-CRC.
We identified mutations in genes in IBD-CRCs with hypermutation that might be
targeted therapeutically. These approaches would complement and individualize
surveillance and treatment programs. Clin Cancer Res; 24(20); 5133-42. (c)2018
AACR.
PMID- 29950350
TI - IFNgamma-induced Chemokines Are Required for CXCR3-mediated T-Cell Recruitment
and Antitumor Efficacy of Anti-HER2/CD3 Bispecific Antibody.
AB - Purpose: The response to cancer immune therapy is dependent on endogenous tumor
reactive T cells. To bypass this requirement, CD3-bispecific antibodies have been
developed to induce a polyclonal T-cell response against the tumor. Anti-HER2/CD3
T-cell-dependent bispecific (TDB) antibody is highly efficacious in the treatment
of HER2-overexpressing tumors in mice. Efficacy and immunologic effects of anti
HER2/CD3 TDB were investigated in mammary tumor model with very few T cells prior
treatment. We further describe the mechanism for TDB-induced T-cell recruitment
to tumors.Experimental Design: The immunologic effects and the mechanism of CD3
bispecific antibody-induced T-cell recruitment into spontaneous HER2
overexpressing mammary tumors was studied using human HER2 transgenic,
immunocompetent mouse models.Results: Anti-HER2/CD3 TDB treatment induced an
inflammatory response in tumors converting them from poorly infiltrated to an
inflamed, T-cell abundant, phenotype. Multiple mechanisms accounted for the TDB
induced increase in T cells within tumors. TDB treatment induced CD8+ T-cell
proliferation. T cells were also actively recruited post-TDB treatment by
IFNgamma-dependent T-cell chemokines mediated via CXCR3. This active T-cell
recruitment by TDB-induced chemokine signaling was the dominant mechanism and
necessary for the therapeutic activity of anti-HER2/CD3 TDB.Conclusions: In
summary, we demonstrate that the activity of anti-HER2/CD3 TDB was not dependent
on high-level baseline T-cell infiltration. Our results suggest that anti
HER2/CD3 TDB may be efficacious in patients and indications that respond poorly
to checkpoint inhibitors. An active T-cell recruitment mediated by TDB-induced
chemokine signaling was the major mechanism for T-cell recruitment. Clin Cancer
Res; 1-12. (c)2018 AACR.
PMID- 29950349
TI - Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC:
A Pilot Trial.
AB - Purpose: Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose
(poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like
receptor-3 and MDA-5 that can activate immune cells, such as dendritic cells, and
trigger natural killer cells to kill tumor cells.Patients and Methods: In this
pilot study, eligible patients included those with recurrent metastatic disease
in whom prior systemic therapy (head and neck squamous cell cancer and melanoma)
failed. Patients received 2 treatment cycles, each cycle consisting of 1 mg poly
ICLC 3* weekly intratumorally (IT) for 2 weeks followed by intramuscular (IM)
boosters biweekly for 7 weeks, with a 1-week rest period. Immune response was
evaluated by immunohistochemistry (IHC) and RNA sequencing (RNA-seq) in tumor and
blood.Results: Two patients completed 2 cycles of IT treatments, and 1 achieved
clinical benefit (stable disease, progression-free survival 6 months), whereas
the remainder had progressive disease. Poly-ICLC was well tolerated, with
principal side effects of fatigue and inflammation at injection site (7 ug/mL, 7/63 (11%) were in relapse vs 46/143 (32%) in remission.
Change in management resulted from 43/206 (21%) TLIs in 31/60 (52%) children: 21
dose escalations, 12 de-escalations and 10 changed to adalimumab. Of 31
postinduction TLIs, 15/17 (88%) children with TLI >7 ug/mL achieved clinical and
biochemical remission for the duration of therapy (median 14 months), while 4/5
(80%) children with TLI <3 ug/mL required early dose escalation. Combination
therapy with thiopurines (TP) (median TLI 4.9 ug/mL) versus methotrexate (MTX)
(median TLI 5.2 ug/mL) achieved comparable levels with no difference in relapse
frequency. CONCLUSIONS: Routine, proactive TLIs guide optimal management in
children with CD. Postinduction and during maintenance, levels <3 ug/mL were
associated with relapse and levels >7 ug/mL with sustained remission. Combination
IS with TP and MTX appears to offer comparable TLI and ADA rates.
PMID- 29950354
TI - Question 2: Vitamin D intake for preterm infants: how much do they really need?
PMID- 29950355
TI - Davener's dermatosis.
PMID- 29950356
TI - Perforated caecal carcinoma masquerading as lower limb necrotising fasciitis:
lessons learnt.
AB - A 69-year-old man was admitted with non-resolving right leg cellulitis.
Subsequent skin changes over the calf and discharging pus suggested necrotising
fasciitis. After several wound debridements of the leg and imaging, the patient
was found to have an iliopsoas abscess due to a metastatic perforated caecal
tumour extending along the medial thigh to the calf. No micro-organisms
indicative of typical necrotising fasciitis were isolated from the wound. The
patient had an ileocaecal resection, and his leg was reconstructed with a split
thickness skin graft. He continues to do well postoperatively. This case
highlights key lessons when dealing with an unusual presentation leading to
challenges in diagnosis such as: (1) the need for good interspecialty liaison,
(2) prompt senior review and plan, and (3) 'thinking outside the box' when faced
with a diagnostic challenge.
PMID- 29950357
TI - 'Toxic' ST elevation.
PMID- 29950358
TI - Hidden burden of osteoporosis in alpha-1 antitrypsin deficiency.
AB - This is a reminder of a rare cause of osteoporosis that remains widely
underdiagnosed and lacks specific evidence on its optimal management. We bring a
case report of a patient presenting with erectile dysfunction and high
testosterone level but also elevated sex-hormone binding globulin hence low free
androgen index as well as evidence of organ specific hypogonadal side effects
such as osteoporosis. A unifying diagnosis of alpha-1 antitrypsin deficiency
(AATD) brought together his coexistent mild chronic obstructive pulmonary disease
as well as a new finding of previously unrecognised liver disease. This case
highlights the uncertainties over the mechanism of osteoporosis in AATD as well
as the controversies over best way to manage it. The efficacy of testosterone
replacement in managing osteoporosis in the context of AATD remains untested.
National registries for AATD would be best placed at gathering further evidence
in this area.
PMID- 29950359
TI - Severe, reversible dysphagia and malnutrition in a patient with tumour-induced
hypophosphataemia.
AB - Up to 20% of hospitalised patients may have low serum phosphate concentrations.
In certain groups, such as patients with chronic alcohol overconsumption, severe
trauma or sepsis, the prevalence may be 30%-50%. Profound hypophosphataemia is
less common, but may lead to severe physiological disturbances. In rare cases,
hypophosphataemia is caused by phosphaturic substances excreted from a tumour.
Osteomalacia with chronic bone pain and fractures, as well as muscle weakness, is
common in such patients. The tumours are often small and difficult to detect.
Studies suggest that fibroblast growth factor 23 is a reliable marker for
detection of these tumours. Persistent hypophosphatemia unresponsive to
supplements should raise clinical alertness. With complete resection of the
neoplasm, the symptoms rapidly reverse. If the tumour cannot be removed,
treatment relies on supplementation with phosphate and active vitamin D
compounds. We present a case report of a patient with severe hypophosphataemia,
osteomalacia, dysphagia and malnutrition.
PMID- 29950360
TI - Successful treatment of intractable visual hallucinations with 5-HT 2A antagonist
ketanserin.
AB - Hallucinations, visual, auditory or in another sensory modality, often respond
well to treatment in patients with schizophrenia. Some, however, do not and can
be very chronic and debilitating. We present a patient with schizophrenia with
intractable hallucinations despite state of the art care, including high-dose
clozapine and transcranial magnetic stimulation. Based on the possible role of
the 5-HT2A receptor in hallucinations, we treated her with the antihypertensive
drug ketanserin, a 5-HT2A receptor antagonist.This significantly reduced her
visual but not her auditory hallucinations, suggesting a possible role of the
5HT2A receptor in the pathophysiology of specifically visual hallucinations. This
is the first time ketanserin has been described to successfully reduce visual
hallucinations in a patient with schizophrenia.
PMID- 29950361
TI - Post-traumatic pseudoaneurysm of brachial artery in multiple hereditary
exostoses.
AB - Pseudoaneurysms adjacent to exostoses have been commonly reported in the femoral
and popliteal arteries and only rarely in the upper extremity. We describe a case
of an 18-year-old man with multiple hereditary exostoses who developed a brachial
artery pseudoaneurysm after minor trauma to his right upper arm, adjacent to a
known lesion. He was referred to a vascular surgeon who removed the
pseudoaneurysm and repaired the artery with a saphenous vein graft. We encourage
a high suspicion of vascular injury even after minor trauma when an
osteochondroma is adjacent to a vascular structure.
PMID- 29950362
TI - Total hip arthroplasty infection caused by an unusual organism, Salmonella; its
successful management and literature review.
AB - Prosthetic joint infection due to Salmonella spp is rare. Here we report an acute
case of Salmonella enteritidis infection of a total hip arthroplasty in a man
taking immunosuppressant medication. He was managed with antibiotics and two
stage revision surgery.
PMID- 29950363
TI - Long-term complete remission of a patient with high grade neuroendocrine
carcinoma of ampulla of Vater.
AB - We describe a case report of a 53-year-old man with a 5-months history of
progressive jaundice and upper abdominal pain. The patient was further evaluated
and finally diagnosed with a high-grade ampullary neuroendocrine tumour (based on
endoscopic-guided biopsy). Thereafter, he underwent pancreatoduodenectomy and
adjuvant platinum-based chemotherapy. This extremely rare case presents his long
lasting disease-free survival compared with similar cases; this case report
exemplifies a new, potentially efficient method for treating high-grade papillary
neuroendocrine tumour and may pave the way for further clinical trials utilising
this blueprint in the treatment of related conditions.
PMID- 29950364
TI - Giant arachnoid granulation with a thrombosed dural arteriovenous fistula.
AB - Arachnoid granulations are common incidentally detected small dural lesions which
are usually asymptomatic and follow cerebrospinal fluid density/signal intensity
on CT/MRI. Such lesions reaching a size of more than 1 cm are termed as giant
arachnoid granulations (GAGs) which have been previously reported to cause venous
hypertension and headaches. We report a case of GAG involving the proximal half
of the superior sagittal sinus in a 45-year-old male patient which was associated
with left temporal thrombosed dural arteriovenous fistula (AVF) whose thrombosed
draining veins were seen converging towards the site of GAG. The patient
presented with three episodes of generalised tonic-clonic seizures and improved
with conservative treatment. No reports of such association of GAG with AVF is
available in the literature, and we believe it could have occurred due to venous
hypertension induced by GAG.
PMID- 29950365
TI - Ciliary body tumour as the presenting manifestation of metastatic non-small cell
adenocarcinoma of lung.
AB - We report a rare case of ciliary body metastasis from adenocarcinoma of the lung.
Although the metastatic nodule was seen over the surface of the iris near the
angle of anterior chamber, ultrasonography confirmed its origin from the ciliary
body. Uveal metastasis may be the first sign of lung cancer.
PMID- 29950366
TI - Non-arteritic anterior ischaemic optic neuropathy secondary to menorrhagia in a
young healthy woman.
AB - Non-arteritic anterior ischaemic optic neuropathy (NAION) may develop due to
severe anaemia and hypotension which is seen in acute blood loss. The devastating
visual loss is often irreversible. We report a case of NAION in a 20-year-old
healthy woman, who presented on the third day of a heavy menstrual cycle with
hypovolaemic shock. On day 2 of admission, she had sudden right eye blurring of
vision at the superior field on awakening from sleep. Funduscopy revealed a pale
and swollen right optic disc. There was a dense right superior altitudinal visual
field defect. Her haemoglobin level was low (3.6 g/dL), but she refused blood
transfusion due to her religious belief (Jehovah's Witness) and opted for
conservative management. She later developed right optic atrophy with persistent
visual field defect despite an improved haemoglobin level of 10.5 g/dL.
PMID- 29950367
TI - Unusual foreign body impacted in the upper oesophagus: original technique for
transoral extraction.
AB - Foreign body ingestion is a common event; in the adult population, most
ingestions occur in patients with mental disability, psychiatric disorders,
alcohol intoxication or in prisoners seeking secondary gain. Removal through
flexible endoscopy is generally the first-line approach but rescue oesophagotomy
may be necessary for foreign bodies impacted in the upper oesophagus. A 27-year
old man was admitted in the emergency room after intentional ingestion of a
wooden spherical object with a central hole. A total body CT scan showed that the
object was completely obstructing the upper oesophageal lumen but there were no
signs of perforation. In the operating room, a Weerda diverticuloscope and a 5 mm
0 degrees telescope were used to visualise the foreign body under general
anaesthesia. A standard endoscopic biopsy forceps was passed through the hole of
the sphere and was retracted with the jaws open allowing transoral extraction
without complications.
PMID- 29950368
TI - Steroid-induced protracted severe ocular hypertension in a 14-year-old girl.
AB - Steroid-induced ocular hypertension (SIOH) is a challenging entity in paediatric
age, with many being refractory to medical therapy. Literature is scarce about
surgical options in these cases. A 14-year-old girl with bilateral uveitis and
macular oedema had received an intravitreal and subconjunctival triamcinolone
injection in the right (OD) and left (OS) eye, respectively. While the steroid
was effective in resolving the oedema, intraocular pressure (IOP) increased to
about 40 mm Hg OD and 34 mm Hg OS, despite being under maximal IOP-lowering
therapy. An initial conservative approach was preferred due to the young patient
age and given that most cases of SIOH are transient. However, progressive
structural changes were documented, and bilateral sequential minimally invasive
glaucoma surgery (MIGS: XEN gel stent) was taken. With a follow-up of 6 months,
the patient is drug-free with IOP around 14 mm Hg. This report discusses the role
and efficacy of MIGS in a paediatric case of SIOH.
PMID- 29950370
TI - Solid pseudopapillary neoplasm of pancreas: an unusual aetiology for
haematochezia.
AB - Solid pseudopapillary neoplasm of the pancreas is a rare condition. It is mostly
seen among young women, with abdominal pain as the presenting complaint. This is
a case of a young woman who presented with haematochezia, and was found to have
splenic vein thrombosis and left-sided portal hypertension as a result of mass
lesion at the tail of the pancreas which was diagnosed as solid pseudopapillary
neoplasm.
PMID- 29950369
TI - Stage 1 small cell cancer of the vagina.
AB - This is the case of a 56-year-old white woman with a medical history significant
for chronic obstructive pulmonary disease, migraine, hypertension, tobacco abuse
and hypercholesterolaemia. Her surgical history is significant for total
hysterectomy and bilateral salpingo-oophorectomy for diffuse endometriosis. The
patient presented with a vaginal lesion. The biopsy was positive for primary
vaginal small cell carcinoma and human papilloma virus (HPV). Initial staging
positron emission tomography (PET) scan confirmed stage 1 disease. The patient
was started on chemotherapy with cisplatin and etoposide for four cycles,
followed by concurrent chemotherapy with cisplatin/taxol and radiation therapy.
PMID- 29950371
TI - Pituitary 'pseudotumor': an under-recognised complication of undertreated primary
hypothyroidism.
PMID- 29950372
TI - Acute torsion of a wandering spleen: a paediatric emergency.
PMID- 29950373
TI - Use of indocyanine green dye clearance in a patient with liver cirrhosis
undergoing hepatectomy: a clinical image.
PMID- 29950374
TI - Spontaneous bilateral perirenal and splenic haematoma in childhood onset
polyarteritis nodosa.
AB - Spontaneous bilateral perirenal haematoma, as well as splenic haematoma, are rare
occasions in polyarteritis nodosa (PAN). We report a case of a young man, who
suffered from various typical and atypical manifestations of PAN since childhood.
The diagnosis was delayed due to symptoms mimicking with other clinical
conditions. Finally, the diagnosis was confirmed when presented with perirenal
and splenic haematoma and was managed successfully.
PMID- 29950375
TI - Late-onset TNF receptor-associated periodic syndrome presenting as recurrent
urticarial rash and lymph nodes.
PMID- 29950376
TI - Case of giant left atrium from congestive heart failure.
PMID- 29950377
TI - How to do it: setting up a PrEP service in an integrated sexual reproductive
health service setting.
AB - Pre-exposure prophylaxis for HIV (PrEP) has been shown to reduce transmission of
HIV in a number of trials; however, there is limited evidence regarding the
optimal way to deliver PrEP through pre-existing UK services, particularly
through fully integrated drop-in sexual health service models. PrEP in the form
of Truvada was launched in Wales in July 2017. We set up a PrEP service to be
delivered via our drop-in integrated sexual reproductive health service. In the
first 5 months of PrEP service provision, we found unforeseen levels of
comorbidity, polypharmacy and renal impairment in our cohort of PrEP patients. As
a result, we have altered our service model and all patients are now followed up
in booked appointment PrEP clinics run by members of the HIV team. Those patients
with estimated glomerular filtration rate (eGFR) of 60-70 mL/min or with eGFR of
60-80 mL/min and with comorbidities impacting on renal function are monitored
every 4-6 weeks initially, and PrEP has been incorporated into our pre-existing
virtual HIV renal clinic for discussion with a renal physician. The PrEP team
clinicians report that monitoring and managing the PrEP cohort is now easier in
its appointment-only format, although some patients have reported that they would
prefer a drop-in system.
PMID- 29950378
TI - Sex with a transgender or gender diverse person among patients attending a sexual
health centre in Melbourne, Australia.
AB - OBJECTIVES: All males and females attending the Melbourne Sexual Health Centre
(MSHC) from August 2017 were asked whether they had had sex with a transgender or
gender diverse (TGD) person using computer-assisted self-interviewing (CASI). We
aimed to verify the self-reported responses via chart review. The secondary aim
of this study was to identify whether having sex with a TGD person was associated
with STI risk. METHODS: This was a retrospective chart analysis of patients
visiting MSHC between August and December 2017. Chart review was performed to
verify the self-reported responses. Multivariable logistic regression was
performed to examine the association between having sex with a TGD person and
patients' characteristics and STI risk. RESULTS: Of the 10 100 male and female
consultations, the proportion who reported having sex with a TGD person was 111
(1.0%) and was higher among males (1.3%) than females (0.6%) (p=0.001). After
chart review, we could verify 66.9% of the responses, more for males (75.2%) than
females (45.2%) (p<0.001). Of the 6822 males, men aged >=35 years (adjusted
OR=2.2; 95% CI 1.1 to 4.1) were more likely to have sex with a TGD person
compared with men aged <=24 years, after adjusting for confounding factors. Sex
with a TGD person was not associated with sexual orientation in males. Of the
3278 females, gay and bisexual females had 13.7-fold (95% CI 5.1 to 37.0) higher
odds of having sex with a TGD person than heterosexual females. There was no
association between chlamydia positivity and sex with a TGD person in both males
and females. CONCLUSION: When a question on TGD partners is asked as part of
routine sexual history using CASI, the majority of responses could be verified.
TGD partners were most commonly reported among males. These findings underscore
the value of asking patients about sex with TGD partners.
PMID- 29950379
TI - Serum-Mediated Cleavage of Bacillus anthracis Protective Antigen Is a Two-Step
Process That Involves a Serum Carboxypeptidase.
AB - Much of our understanding of the activity of anthrax toxin is based on in vitro
systems, which delineate the interaction between Bacillus anthracis toxins and
the cell surface. However, these systems fail to account for the intimate
association of B. anthracis with the circulatory system, including the
contribution of serum proteins to the host response and processing of anthrax
toxins. Using a variety of immunological techniques to inhibit serum processing
of B. anthracis protective antigen (PA) along with mass spectrometry analysis, we
demonstrate that serum digests PA via 2 distinct reactions. In the first
reaction, serum cleaves PA83 into 2 fragments to produce PA63 and PA20 fragments,
similarly to that observed following furin digestion. This is followed by
carboxypeptidase-mediated removal of the carboxy-terminal arginine and lysines
from PA20IMPORTANCE Our findings identify a serum-mediated modification of PA20
that has not been previously described. These observations further imply that the
processing of PA is more complex than currently thought. Additional study is
needed to define the contribution of serum processing of PA to the host response
and individual susceptibility to anthrax.
PMID- 29950380
TI - Clostridium difficile Lipoprotein GerS Is Required for Cortex Modification and
Thus Spore Germination.
AB - Clostridium difficile, also known as Clostridioides difficile, is a Gram
positive, spore-forming bacterium that is a leading cause of antibiotic
associated diarrhea. C. difficile infections begin when its metabolically dormant
spores germinate to form toxin-producing vegetative cells. Successful spore
germination depends on the degradation of the cortex, a thick layer of modified
peptidoglycan that maintains dormancy. Cortex degradation is mediated by the SleC
cortex lytic enzyme, which is thought to recognize the cortex-specific
modification muramic-delta-lactam. C. difficile cortex degradation also depends
on the Peptostreptococcaceae-specific lipoprotein GerS for unknown reasons. In
this study, we tested whether GerS regulates production of muramic-delta-lactam
and thus controls the ability of SleC to recognize its cortex substrate. By
comparing the muropeptide profiles of DeltagerS spores to those of spores lacking
either CwlD or PdaA, both of which mediate cortex modification in Bacillus
subtilis, we determined that C. difficile GerS, CwlD, and PdaA are all required
to generate muramic-delta-lactam. Both GerS and CwlD were needed to cleave the
peptide side chains from N-acetylmuramic acid, suggesting that these two factors
act in concert. Consistent with this hypothesis, biochemical analyses revealed
that GerS and CwlD directly interact and that CwlD modulates GerS incorporation
into mature spores. Since DeltagerS, DeltacwlD, and DeltapdaA spores exhibited
equivalent germination defects, our results indicate that C. difficile spore
germination depends on cortex-specific modifications, reveal GerS as a novel
regulator of these processes, and highlight additional differences in the
regulation of spore germination in C. difficile relative to B. subtilis and other
spore-forming organisms.IMPORTANCE The Gram-positive, spore-forming bacterium
Clostridium difficile is a leading cause of antibiotic-associated diarrhea.
Because C. difficile is an obligate anaerobe, its aerotolerant spores are
essential for transmitting disease, and their germination into toxin-producing
cells is necessary for causing disease. Spore germination requires the removal of
the cortex, a thick layer of modified peptidoglycan that maintains spore
dormancy. Cortex degradation is mediated by the SleC hydrolase, which is thought
to recognize cortex-specific modifications. Cortex degradation also requires the
GerS lipoprotein for unknown reasons. In our study, we tested whether GerS is
required to generate cortex-specific modifications by comparing the cortex
composition of DeltagerS spores to the cortex composition of spores lacking two
putative cortex-modifying enzymes, CwlD and PdaA. These analyses revealed that
GerS, CwlD, and PdaA are all required to generate cortex-specific modifications.
Since loss of these modifications in DeltagerS, DeltacwlD, and DeltapdaA mutants
resulted in spore germination and heat resistance defects, the SleC cortex lytic
enzyme depends on cortex-specific modifications to efficiently degrade this
protective layer. Our results further indicate that GerS and CwlD are mutually
required for removing peptide chains from spore peptidoglycan and revealed a
novel interaction between these proteins. Thus, our findings provide new
mechanistic insight into C. difficile spore germination.
PMID- 29950381
TI - Clostridium difficile Alters the Structure and Metabolism of Distinct Cecal
Microbiomes during Initial Infection To Promote Sustained Colonization.
AB - Susceptibility to Clostridium difficile infection (CDI) is primarily associated
with previous exposure to antibiotics, which compromise the structure and
function of the gut bacterial community. Specific antibiotic classes correlate
more strongly with recurrent or persistent C. difficile infection. As such, we
utilized a mouse model of infection to explore the effect of distinct antibiotic
classes on the impact that infection has on community-level transcription and
metabolic signatures shortly following pathogen colonization and how those
changes may associate with persistence of C. difficile Untargeted metabolomic
analysis revealed that C. difficile infection had significantly larger impacts on
the metabolic environment across cefoperazone- and streptomycin-pretreated mice,
which became persistently colonized compared to clindamycin-pretreated mice,
where infection quickly became undetectable. Through metagenome-enabled
metatranscriptomics, we observed that transcripts for genes associated with
carbon and energy acquisition were greatly reduced in infected animals,
suggesting that those niches were instead occupied by C. difficile Furthermore,
the largest changes in transcription were seen in the least abundant species,
indicating that C. difficile may "attack the loser" in gut environments where
sustained infection occurs more readily. Overall, our results suggest that C.
difficile is able to restructure the nutrient-niche landscape in the gut to
promote persistent infection.IMPORTANCEClostridium difficile has become the most
common single cause of hospital-acquired infection over the last decade in the
United States. Colonization resistance to the nosocomial pathogen is primarily
provided by the gut microbiota, which is also involved in clearing the infection
as the community recovers from perturbation. As distinct antibiotics are
associated with different risk levels for CDI, we utilized a mouse model of
infection with 3 separate antibiotic pretreatment regimens to generate
alternative gut microbiomes that each allowed for C. difficile colonization but
varied in clearance rate. To assess community-level dynamics, we implemented an
integrative multi-omics approach that revealed that infection significantly
changed many aspects of the gut community. The degree to which the community
changed was inversely correlated with clearance during the first 6 days of
infection, suggesting that C. difficile differentially modifies the gut
environment to promote persistence. This is the first time that metagenome
enabled metatranscriptomics have been employed to study the behavior of a host
associated microbiota in response to an infection. Our results allow for a
previously unseen understanding of the ecology associated with C. difficile
infection and provide the groundwork for identification of context-specific
probiotic therapies.
PMID- 29950383
TI - Correction for Omrane et al., "Plasticity of the MFS1 Promoter Leads to Multidrug
Resistance in the Wheat Pathogen Zymoseptoria tritici".
PMID- 29950382
TI - Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals
Differential Expression of Antibiotic Resistance Determinants between Men and
Women.
AB - Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually
transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) of
N. gonorrhoeae worldwide has resulted in limited therapeutic choices for this
infection. Men who seek treatment often have symptomatic urethritis; in contrast,
gonococcal cervicitis in women is usually minimally symptomatic, but may progress
to pelvic inflammatory disease. Previously, we reported the first analysis of
gonococcal transcriptome expression determined in secretions from women with
cervical infection. Here, we defined gonococcal global transcriptional responses
in urethral specimens from men with symptomatic urethritis and compared these
with transcriptional responses in specimens obtained from women with cervical
infections and in vitro-grown N. gonorrhoeae isolates. This is the first
comprehensive comparison of gonococcal gene expression in infected men and women.
RNA sequencing analysis revealed that 9.4% of gonococcal genes showed increased
expression exclusively in men and included genes involved in host immune cell
interactions, while 4.3% showed increased expression exclusively in women and
included phage-associated genes. Infected men and women displayed comparable
antibiotic-resistant genotypes and in vitro phenotypes, but a 4-fold higher
expression of the Mtr efflux pump-related genes was observed in men. These
results suggest that expression of AMR genes is programed genotypically and also
driven by sex-specific environments. Collectively, our results indicate that
distinct N. gonorrhoeae gene expression signatures are detected during genital
infection in men and women. We propose that therapeutic strategies could target
sex-specific differences in expression of antibiotic resistance genes.IMPORTANCE
Recent emergence of antimicrobial resistance of Neisseria gonorrhoeae worldwide
has resulted in limited therapeutic choices for treatment of infections caused by
this organism. We performed global transcriptomic analysis of N. gonorrhoeae in
subjects with gonorrhea who attended a Nanjing, China, sexually transmitted
infection (STI) clinic, where antimicrobial resistance of N. gonorrhoeae is high
and increasing. We found that N. gonorrhoeae transcriptional responses to
infection differed in genital specimens taken from men and women, particularly
antibiotic resistance gene expression, which was increased in men. These sex
specific findings may provide a new approach to guide therapeutic interventions
and preventive measures that are also sex specific while providing additional
insight to address antimicrobial resistance of N. gonorrhoeae.
PMID- 29950384
TI - Insights Into the Role of Regional Proteoglycan Metabolism in Thoracic Aortic
Aneurysms.
PMID- 29950385
TI - 2017 Reviewer Acknowledgment.
PMID- 29950387
TI - Correction to: Mitochondrial Respiration Is Reduced in Atherosclerosis, Promoting
Necrotic Core Formation and Reducing Relative Fibrous Cap Thickness.
PMID- 29950388
TI - Correction to: Effects of Increasing Exercise Intensity and Dose on Multiple
Measures of HDL (High-Density Lipoprotein) Function.
PMID- 29950386
TI - Renin-Angiotensin System and Cardiovascular Functions.
PMID- 29950389
TI - Side branching and luminal lineage commitment by ID2 in developing mammary
glands.
AB - Mammary glands develop through primary ductal elongation and side branching to
maximize the spatial area. Although primary ducts are generated by bifurcation of
terminal end buds, the mechanism through which side branching occurs is still
largely unclear. Here, we show that inhibitor of DNA-binding 2 (ID2) drives side
branch formation through the differentiation of K6+ bipotent progenitor cells
(BPs) into CD61+ luminal progenitor cells (LPs). Id2-null mice had side-branching
defects, along with developmental blockage of the differentiation of K6+ BPs into
CD61+ LPs. Notably, CD61+ LPs were found in budding and side branches, but not in
terminal end buds. Hormone reconstitution studies using ovariectomized MMTV
hemagglutinin-nuclear localized sequence-tagged Id2 transgenic mice revealed that
ID2 is a key mediator of progesterone, which drives luminal lineage
differentiation and side branching. Our results suggest that CD61 is a marker of
side branches and that ID2 regulates side branch formation by inducing luminal
lineage commitment from K6+ BPs to CD61+ LPs.
PMID- 29950390
TI - Induced cell fate transitions at multiple cell layers configure haustorium
development in parasitic plants.
AB - The haustorium in parasitic plants is an organ specialized for invasion and
nutrient uptake from host plant tissues. Despite its importance, the
developmental processes of haustoria are mostly unknown. To understand the
dynamics of cell fate change and cellular lineage during haustorium development,
we performed live imaging-based marker expression analysis and cell-lineage
tracing during haustorium formation in the model facultative root parasite
Phtheirospermum japonicum Our live-imaging analysis revealed that haustorium
formation was associated with induction of simultaneous cell division in multiple
cellular layers, such as epidermis, cortex and endodermis. In addition, we found
that procambium-like cells, monitored by cell type-specific markers, emerged
within the central region of the haustorium before xylem connection to the host
plant. Our clonal analysis of cell lineages showed that cells in multiple
cellular layers differentiated into procambium-like cells, whereas epidermal
cells eventually transitioned into specialized cells interfacing with the host
plant. Thus, our data provide a cell fate transition map during de novo
haustorium organogenesis in parasitic plants.
PMID- 29950392
TI - Implementation of patient-centered prescription labeling in a safety-net
ambulatory care network.
AB - PURPOSE: An initiative to implement patient-centered medication labeling at 4
pharmacies within a publicly funded safety-net healthcare system is described.
SUMMARY: Medication nonadherence negatively affects patient outcomes and safety.
Nonadherence has been attributed to poor understanding of instructions on
medication labels. Research has demonstrated that patient-centered labeling (PCL)
can improve adherence and produce safer medication-taking practices. As part of a
mixed-methods study by a safety-net health system, audits of nearly 9,000
prescription labels generated at 4 pharmacy sites, as well as interviews with 6
stakeholder informants, were conducted to determine PCL adoption rates and
factors contributing to success. Descriptive statistics were used to analyze
audit data; constructs of the Consolidated Framework for Implementation Research
were used to analyze interview data. Among the 4 sites, 3 pharmacies successfully
converted more than 85% of audited prescriptions to a PCL format; 1 pharmacy
converted less than 25% of prescriptions. Barriers to implementation included
pharmacists' reluctance to modify prescriber instructions and inadequate real
time data on conversion rates. Interviewees perceived that leadership and policy
directives promoted PCL conversion efforts. Successful pharmacies used adaptable
software, had closer communication networks with prescribers, and/or used
automation to facilitate PCL conversion. CONCLUSION: Three pharmacies
successfully converted more than 85% of labels for audited prescriptions to a PCL
format; 1 pharmacy converted less than 25% of prescriptions. Barriers to
implementation included pharmacists' reluctance to modify prescriber
instructions, inadequate real-time data on conversation rates, and lack of
customizable software to automate changes.
PMID- 29950391
TI - Insulin signaling modulates border cell movement in Drosophila oogenesis.
AB - As collective cell migration is intimately involved in different aspects of
metazoan development, molecular mechanisms underlying this process are being
explored in a variety of developmental contexts. Border cell (BC) migration
during Drosophila oogenesis has emerged as an excellent genetic model for
studying collective cell migration. BCs are of epithelial origin but acquire
partial mesenchymal characteristics before migrating as a group towards the
oocyte. Here, we report that insulin signaling modulates collective BC movement
during Drosophila oogenesis. Supporting the involvement of Insulin pathway, we
demonstrate that compromising Insulin-like Receptor (InR) levels in BCs, inhibits
their migration. Furthermore, we show that canonical Insulin signaling pathway
components participate in this process. Interestingly, visualization of InR
depleted BC clusters, using time-lapse imaging, revealed a delay in detachment of
BC clusters from the surrounding anterior follicle cells and altered protrusion
dynamics. Lastly, based on genetic interactions between InR, the polarity
determinant, par-1 and a regulatory subunit of Drosophila Myosin (spaghetti
squash), we propose that Insulin signaling likely influences par-1 activity to
engineer border cell detachment and subsequent movement via Drosophila Myosin.
PMID- 29950393
TI - Prevalence of wireless smart-pump drug library update delays.
AB - PURPOSE: Results of a study to estimate the prevalence and severity of delays in
wireless updates of smart-pump drug libraries across a large group of U.S.
hospitals are reported. METHODS: A prolonged smart-pump drug library update may
result in patient harm if a pump is programmed with an incorrect limit setting at
the time of drug administration. A retrospective study was conducted using smart
pump alert data extracted from the Regenstrief National Center for Medical Device
Informatics (REMEDI) database. The study sample consisted of 49 hospitals in 5
states across the Midwest and Kentucky operated by 12 health systems; all the
facilities used a specific brand of smart pump (BD Alaris, Beckton, Dickinson and
Company) capable of generating alert data and had consistently contributed alert
data to the REMEDI database over a 2-year period. An update delay was defined as
the interval from the time a drug library version was replaced to the time of the
last infusion alert triggered by the previous version during the study period.
RESULTS: Of the 12 health systems, 11 were found to have had drug library update
delays during the study period, with delay medians ranging from 22 to 192 days.
The overall delay minimum and maximum durations were 0 and 661 days. CONCLUSION:
Substantial delays in completion of wireless updates of smart-pump drug libraries
were common across a group of hospitals of various sizes.
PMID- 29950394
TI - Pseudotime Ordering of Single Human beta-Cells Reveals States of Insulin
Production and Unfolded Protein Response.
AB - Proinsulin is a misfolding-prone protein, making its biosynthesis in the
endoplasmic reticulum (ER) a stressful event. Pancreatic beta-cells overcome ER
stress by activating the unfolded protein response (UPR) and reducing insulin
production. This suggests that beta-cells transition between periods of high
insulin biosynthesis and UPR-mediated recovery from cellular stress. We now
report the pseudotime ordering of single beta-cells from humans without diabetes
detected by large-scale RNA sequencing. We identified major states with 1) low
UPR and low insulin gene expression, 2) low UPR and high insulin gene expression,
or 3) high UPR and low insulin gene expression. The latter state was enriched for
proliferating cells. Stressed human beta-cells do not dedifferentiate and show
little propensity for apoptosis. These data suggest that human beta-cells
transition between states with high rates of biosynthesis to fulfill the body's
insulin requirements to maintain normal blood glucose levels and UPR-mediated
recovery from ER stress due to high insulin production.
PMID- 29950395
TI - Patients or families raising the alarm are vital voices that must be heard, not
problems to be managed.
PMID- 29950397
TI - A Toddler With Treatment-Resistant Iron Deficiency Anemia.
AB - A 19-month-old girl with a history of asthma and atopic dermatitis presented to
her pediatrician because of parental concerns of pallor and fatigue. On dietary
history, it was discovered that she was a picky eater and consumed 26 oz of
homogenous milk daily. Her physical examination was unremarkable aside from
pallor, and both her height and weight plotted between the 50th and 75th
percentile for age. Therefore, she was investigated for iron deficiency anemia
and indeed her blood work was consistent. Despite appropriate iron
supplementation and dietary milk restriction, there was no improvement in her
hemoglobin or iron studies. Our expert panel examines the case and offers a
differential diagnosis for a child presenting with treatment-resistant iron
deficiency anemia.
PMID- 29950396
TI - Prospective external validation of the Predicting Out-of-OFfice Blood Pressure
(PROOF-BP) strategy for triaging ambulatory monitoring in the diagnosis and
management of hypertension: observational cohort study.
AB - OBJECTIVE: To prospectively validate the Predicting Out-of-OFfice Blood Pressure
(PROOF-BP) algorithm to triage patients with suspected high blood pressure for
ambulatory blood pressure monitoring (ABPM) in routine clinical practice. DESIGN:
Prospective observational cohort study. SETTING: 10 primary care practices and
one hospital in the UK. PARTICIPANTS: 887 consecutive patients aged 18 years or
more referred for ABPM in routine clinical practice. All underwent ABPM and had
the PROOF-BP applied. MAIN OUTCOME MEASURES: The main outcome was the proportion
of participants whose hypertensive status was correctly classified using the
triaging strategy compared with the reference standard of daytime ABPM. Secondary
outcomes were the sensitivity, specificity, and area under the receiver operator
characteristic curve (AUROC) for detecting hypertension. RESULTS: The mean age of
participants was 52.8 (16.2) years. The triaging strategy correctly classified
hypertensive status in 801 of the 887 participants (90%, 95% confidence interval
88% to 92%) and had a sensitivity of 97% (95% confidence interval 96% to 98%) and
specificity of 76% (95% confidence interval 71% to 81%) for hypertension. The
AUROC was 0.86 (95% confidence interval 0.84 to 0.89). Use of triaging, rather
than uniform referral for ABPM in routine practice, would have resulted in 435
patients (49%, 46% to 52%) being referred for ABPM and the remainder managed on
the basis of their clinic measurements. Of these, 69 (8%, 6% to 10%) would have
received treatment deemed unnecessary had they received ABPM. CONCLUSIONS: In a
population of patients referred for ABPM, this new triaging approach accurately
classified hypertensive status for most, with half the utilisation of ABPM
compared with usual care. This triaging strategy can therefore be recommended for
diagnosis or management of hypertension in patients where ABPM is being
considered, particularly in settings with limited resources.
PMID- 29950398
TI - Just Do It: Incorporating Bedside Teaching Into Every Patient Encounter.
PMID- 29950399
TI - Duplex signaling by CaM and Stac3 enhances CaV1.1 function and provides insights
into congenital myopathy.
AB - CaV1.1 is essential for skeletal muscle excitation-contraction coupling. Its
functional expression is tuned by numerous regulatory proteins, yet underlying
modulatory mechanisms remain ambiguous as CaV1.1 fails to function in
heterologous systems. In this study, by dissecting channel trafficking versus
gating, we evaluated the requirements for functional CaV1.1 in heterologous
systems. Although coexpression of the auxiliary beta subunit is sufficient for
surface-membrane localization, this baseline trafficking is weak, and channels
elicit a diminished open probability. The regulatory proteins calmodulin and
stac3 independently enhance channel trafficking and gating via their interaction
with the CaV1.1 carboxy terminus. Myopathic stac3 mutations weaken channel
binding and diminish trafficking. Our findings demonstrate that multiple
regulatory proteins orchestrate CaV1.1 function via duplex mechanisms. Our work
also furnishes insights into the pathophysiology of stac3-associated congenital
myopathy and reveals novel avenues for pharmacological intervention.
PMID- 29950401
TI - James Munro: Caring about opinions.
PMID- 29950400
TI - A two-step docking site model predicting different short-term synaptic plasticity
patterns.
AB - The strength of synaptic transmission varies during trains of presynaptic action
potentials, notably because of the depletion of synaptic vesicles available for
release. It has remained unclear why some synapses display depression over time,
whereas others facilitate or show a facilitation and depression sequence. Here we
compare the predictions of various synaptic models assuming that several
docking/release sites are acting in parallel. These models show variation of
docking site occupancy during trains of action potentials due to vesicular
release and site replenishment, which give rise to changes in synaptic strength.
To conform with recent studies, we assume an initial docking site occupancy of
<1, thus permitting site occupancy to increase during action potential trains and
facilitation to occur. We consider both a standard one-step model and a more
elaborate model that assumes a predocked state (two-step model). Whereas the one
step model predicts monotonic changes of synaptic strength during a train, the
two-step model allows nonmonotonic changes, including the often-observed
facilitation/depression sequence. Both models predict a partitioning of parameter
space between initially depressing and facilitating synapses. Using data obtained
from interneuron synapses in the cerebellum, we demonstrate an unusual form of
depression/facilitation sequence for very high release probability after
prolonged depolarization-induced transmitter release. These results indicate a
depletion of predocked vesicles in the two-step model. By permitting docking site
occupancy to be <1 at rest, and by incorporating a separate predocked state, we
reveal that docking site models can be expanded to mimic the large variety of
time-dependent changes of synaptic strength that have been observed during action
potential trains. Furthermore, the two-step model provides an effective framework
to identify the specific mechanisms responsible for short-term changes in
synaptic strength.
PMID- 29950402
TI - 50*50*50.
PMID- 29950403
TI - Genetic Regulation of Fibroblast Activation and Proliferation in Cardiac
Fibrosis.
AB - BACKGROUND: Genetic diversity and the heterogeneous nature of cardiac fibroblasts
(CFbs) have hindered characterization of the molecular mechanisms that regulate
cardiac fibrosis. The Hybrid Mouse Diversity Panel offers a valuable tool to
examine genetically diverse cardiac fibroblasts and their role in fibrosis.
METHODS: Three strains of mice (C57BL/6J, C3H/HeJ, and KK/HlJ) were selected from
the Hybrid Mouse Diversity Panel and treated with either isoproterenol (ISO) or
saline by an intraperitoneally implanted osmotic pump. After 21 days, cardiac
function and levels of fibrosis were measured by echocardiography and trichrome
staining, respectively. Activation and proliferation of CFbs were measured by in
vitro and in vivo assays under normal and injury conditions. RNA sequencing was
done on isolated CFbs from each strain. Results were analyzed by Ingenuity
Pathway Analysis and validated by reverse transcription-qPCR,
immunohistochemistry, and ELISA. RESULTS: ISO treatment in C57BL/6J, C3H/HeJ, and
KK/HlJ mice resulted in minimal, moderate, and extensive levels of fibrosis,
respectively (n=7-8 hearts per condition). Isolated CFbs treated with ISO
exhibited strain-specific increases in the levels of activation but showed
comparable levels of proliferation. Similar results were found in vivo, with
fibroblast activation, and not proliferation, correlating with the differential
levels of cardiac fibrosis after ISO treatment. RNA sequencing revealed that CFbs
from each strain exhibit unique gene expression changes in response to ISO. We
identified Ltbp2 as a commonly upregulated gene after ISO treatment. Expression
of LTBP2 was elevated and specifically localized in the fibrotic regions of the
myocardium after injury in mice and in human heart failure patients. CONCLUSIONS:
This study highlights the importance of genetic variation in cardiac fibrosis by
using multiple inbred mouse strains to characterize CFbs and their response to
ISO treatment. Our data suggest that, although fibroblast activation is a
response that parallels the extent of scar formation, proliferation may not
necessarily correlate with levels of fibrosis. In addition, by comparing CFbs
from multiple strains, we identified pathways as potential therapeutic targets
and LTBP2 as a marker for fibrosis, with relevance to patients with underlying
myocardial fibrosis.
PMID- 29950404
TI - Incidence of Hospitalisation for Heart Failure and Case-Fatality Among 3.25
Million People with and without Diabetes.
AB - Background -Recent clinical trials of new glucose-lowering treatments have drawn
attention to the importance of hospitalisation for heart failure as a
complication of diabetes. However, the epidemiology is not well described,
particularly for type 1 diabetes. We examined the incidence and case-fatality of
heart failure hospitalisations in the entire population aged 30 and older
resident in Scotland during 2004 to 2013. Methods -Date and type of diabetes
diagnosis were linked to heart failure hospitalisations and deaths using the
national Scottish registers. Incidence rates and case-fatality were estimated in
regression models (quasi-Poisson and logistic regression respectively). All
estimates are adjusted for age, sex, socio-economic status and calendar-year.
Results -Over the 10-year period of the study, among 3.25 million people there
were 91,429, 22,959 and 1,313 incident heart failure events among those without
diabetes, with type 2, and type 1 diabetes respectively. The crude incidence
rates of heart failure hospitalisation were therefore 2.4, 12.4 and 5.6 per 1000
person-years for these three groups. Heart failure hospitalisation incidence was
higher in people with diabetes, regardless of type, than in people without.
Relative differences were smallest for older men, in whom the difference was
nonetheless large (men aged 80, rate ratio 1.78; 95% CI 1.45 to 2.19). Rates
declined similarly, by 0.2% per calendar-year, in people with type 2 diabetes and
without diabetes. Rates fell faster, however, in those with type 1 diabetes (2.2%
per calendar-year, RR for type 1/calendar-year interaction 0.978; 95% CI 0.959 to
0.998).30-day case-fatality was similar among people with type 2 diabetes and
without diabetes, but was higher in type 1 diabetes for men (OR 0.96; 95% CI 0.95
to 0.96) and women (OR 0.98; 95% CI 0.97 to 0.98). Case-fatality declined over
time for all groups (3.3% per calendar-year, OR per calendar-year 0.967; 95% CI
0.961 to 0.973). Conclusions -Despite falling incidence, particularly in type 1
diabetes, heart failure remains around 2-fold higher than in people without
diabetes, with higher case-fatality in those with type 1 diabetes. These findings
support the view that heart failure is an under-recognised and important
complication in diabetes, particularly for type 1 disease.
PMID- 29950405
TI - A Novel CRISPR/Cas9-Based Cellular Model to Explore Adenylyl Cyclase and cAMP
Signaling.
AB - Functional characterization of adenylyl cyclase (AC) isoforms has proven
challenging in mammalian cells because of the endogenous expression of multiple
AC isoforms and the high background cAMP levels induced by nonselective AC
activators. To simplify the characterization of individual transmembrane AC (mAC)
isoforms, we generated a human embryonic kidney cell line 293 (HEK293) with low
cAMP levels by knocking out two highly expressed ACs, AC3 and AC6, using
CRISPR/Cas9 technology. Stable HEK293 cell lines lacking either AC6 (HEK
ACDelta6) or both AC3 and AC6 (HEK-ACDelta3/6) were generated. Knockout was
confirmed genetically and by comparing cAMP responses of the knockout cells to
the parental cell line. HEK-ACDelta6 and HEK-ACDelta3/6 cells revealed an 85% and
95% reduction in the forskolin-stimulated cAMP response, respectively. Forskolin-
and Galphas-coupled receptor-induced activation was examined for the nine
recombinant mAC isoforms in the HEK-ACDelta3/6 cells. Forskolin-mediated cAMP
accumulation for AC1-6 and AC8 revealed 10- to 250-fold increases over the basal
cAMP levels. All nine mAC isoforms, except AC8, also exhibited significantly
higher cAMP levels than the control cells after Galphas-coupled receptor
activation. Isoform-specific AC regulation by protein kinases and Ca2+/calmodulin
was also recapitulated in the knockout cells. Furthermore, the utility of the HEK
ACDelta3/6 cell line was demonstrated by characterizing the activity of novel AC1
forskolin binding-site mutants. Hence, we have developed a HEK293 cell line
deficient of endogenous AC3 and AC6 with low cAMP background levels for studies
of cAMP signaling and AC isoform regulation.
PMID- 29950406
TI - Real-time visualization and quantification of human Cytomegalovirus replication
in living cells using the ANCHOR DNA labeling technology.
AB - Human cytomegalovirus (HCMV) induces latent life-long infections in all human
populations. Between 30 to nearly 100% of individuals are affected depending on
geographic area and socio-economic conditions. The biology of this virus is
difficult to explore due to its extreme sophistication and the lack of pertinent
animal model. Here we present the first application of the ANCHOR DNA labeling
system to a herpes virus, enabling real time imaging and direct monitoring of
HCMV infection and replication in living human cells. The ANCHOR system is
composed of a protein (OR) which specifically binds to a short, non-repetitive
DNA target sequence (ANCH) and spreads onto neighboring sequences by protein
oligomerization. When OR protein is fused to GFP, its accumulation results in a
site specific fluorescent focus. We have created a recombinant ANCHOR- HCMV
harboring an ANCH target sequence and the gene encoding the cognate OR-GFP fusion
protein. Infection of permissive cells with ANCHOR-HCMV enables visualization of
nearly the complete viral cycle until cell fragmentation and death. Quantitative
analysis of infection kinetics and of viral DNA replication revealed cell-type
specific HCMV behavior and sensitivity to inhibitors. Our results show that the
ANCHOR technology provides an efficient tool for the study of complex DNA viruses
and a new highly promising system for the development of innovative biotechnology
applications.IMPORTANCE The ANCHOR technology is to date the most powerful tool
to follow and quantify the replication of HCMV in living cells and to gain new
insights into its biology. This technology is applicable to virtually any DNA
virus or viruses presenting a dsDNA phase, paving the way to imaging infection in
various cell lines or even in animal models, and opening fascinating fundamental
and applied prospects. Associated to high content automated microscopy, this
technology permitted rapid, robust and precise determination of Ganciclovir IC50
and IC90 on HCMV replication, with minimal hands-on investment. To search for new
antiviral activities, the experiment is easy to up-grade towards efficient and
cost-effective screening of large chemical libraries. Simple infection of
permissive cells with ANCHOR-viruses in the presence of a compound of interest
even provides a first estimation of the stage of the viral cycle this molecule is
acting upon.
PMID- 29950407
TI - Attenuated Herpes Simplex Virus 1 (HSV-1) Expressing a Mutant Form of ICP6
Stimulates a Strong Immune Response That Protects Mice against HSV-1-Induced
Corneal Disease.
AB - We previously isolated a herpes simplex virus 1 (HSV-1) mutant, KOS-NA, that
carries two nonsynonymous mutations in UL39, resulting in L393P and R950H amino
acid substitutions in infected cell protein 6 (ICP6). Our published data studying
KOS-NA pathogenesis strongly suggest that one of these ICP6 substitutions
expressed from KOS-NA, R950H, severely impaired acute viral replication in the
eyes and trigeminal ganglia of mice after inoculation onto the cornea and
consequently impaired establishment and reactivation from latency. Because of its
significant neuroattenuation, we tested KOS-NA as a potential prophylactic
vaccine against HSV-1 in a mouse model of corneal infection. KOS-NA stimulated
stronger antibody and T cell responses than a replication-competent ICP0-null
mutant and a replication-incompetent ICP8-null mutant optimized for
immunogenicity. Immunizations with the ICP0-, ICP8-, and KOS-NA viruses all
reduced replication of wild-type HSV-1 challenge virus in the corneal epithelium
to similar extents. Low immunizing doses of KOS-NA and the ICP8- virus, but not
the ICP0- virus, protected mice against eyelid disease (blepharitis). Notably,
only KOS-NA protected almost completely against corneal disease (keratitis) and
greatly reduced latent infection by challenge virus. Thus, vaccination of mice
with KOS-NA prior to corneal challenge provides significant protection against
HSV-1-mediated disease of the eye, even at a very low immunizing dose. These
results suggest that KOS-NA may be the foundation of an effective prophylactic
vaccine to prevent or limit HSV-1 ocular diseases.IMPORTANCE HSV-1 is a
ubiquitous human pathogen that infects the majority of the world's population.
Although most infections are asymptomatic, HSV-1 establishes lifelong latency in
infected sensory neurons, from which it can reactivate to cause deadly
encephalitis or potentially blinding eye disease. No clinically effective vaccine
is available. In this study, we tested the protective potential of a
neuroattenuated HSV-1 mutant (KOS-NA) as a vaccine in mice. We compared the
effects of immunization with KOS-NA to those of two other attenuated viruses, a
replication-competent (ICP0-) virus and a replication-incompetent (ICP8-) virus.
Our data show that KOS-NA proved superior to the ICP0- and ICP8-null mutants in
protecting mice from corneal disease and latent infection. With its significant
neuroattenuation, severe impairment in establishing latency, and excellent
protective effect, KOS-NA represents a significant discovery in the field of HSV
1 vaccine development.
PMID- 29950408
TI - Cellular Antisilencing Elements Support Transgene Expression from Herpes Simplex
Virus Vectors in the Absence of Immediate Early Gene Expression.
AB - Inactivation of all herpes simplex virus (HSV) immediate early (IE) genes to
eliminate vector cytotoxicity results in rapid silencing of the viral genome,
similar to the establishment of HSV latency. We recently reported that silencing
of a nonviral reporter cassette could be overcome in nonneuronal cells by
positioning the cassette in the viral latency (LAT) locus between resident
chromatin boundary elements. Here, we tested the abilities of the chicken
hypersensitive site 4 insulator and the human ubiquitous chromatin opening
element A2UCOE to promote transgene expression from an IE-gene-inactivated HSV
vector. We found that A2UCOE was particularly active in nonneuronal cells and
reduced reporter promoter occupancy by a repressive histone mark. We determined
whether multiple transgenes could be expressed under the control of different
promoters from different loci of the same virus. The results showed abundant
coexpression of LAT-embedded and A2UCOE-flanked genes in nonneuronal cells. In
addition, a third reporter gene without known protective elements was active in
cultured rat sensory neurons. These findings indicate that cellular antisilencing
sequences can contribute to the expression of multiple genes from separate
promoters in fully IE gene-disabled HSV vectors, providing an opportunity for
therapeutic applications requiring mutually independent expression of different
gene products from a single vector.IMPORTANCE Gene therapy has now entered a
phase of development in which a growing number of recessive single gene defects
can be successfully treated by vector-mediated introduction of a wild-type copy
of the gene into the appropriate tissue. However, many disease conditions, such
as neurodegeneration, cancer, and inflammatory processes, are more complex,
requiring either multiple gene corrections or provision of coordinated gene
activities to achieve a therapeutic outcome. Although herpes simplex virus (HSV)
vectors have the capacity to meet this need, the challenge has been to
genetically engineer the HSV genome in a manner to prevent expression of any
viral genes while retaining the ability to express multiple therapeutic
transgenes under independent transcriptional control. Here, we show that non-HSV
insulator elements can be applied to retain at least transient transgene activity
from multiple viral loci, thereby opening the door for more complex gene therapy
applications in the future.
PMID- 29950409
TI - Transcriptional and Translational Landscape of Equine Torovirus.
AB - The genus Torovirus (subfamily Torovirinae, family Coronaviridae, order
Nidovirales) encompasses a range of species that infect domestic ungulates,
including cattle, sheep, goats, pigs, and horses, causing an acute self-limiting
gastroenteritis. Using the prototype species equine torovirus (EToV), we
performed parallel RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) to
analyze the relative expression levels of the known torovirus proteins and
transcripts, chimeric sequences produced via discontinuous RNA synthesis (a
characteristic of the nidovirus replication cycle), and changes in host
transcription and translation as a result of EToV infection. RNA sequencing
confirmed that EToV utilizes a unique combination of discontinuous and
nondiscontinuous RNA synthesis to produce its subgenomic RNAs (sgRNAs); indeed,
we identified transcripts arising from both mechanisms that would result in
sgRNAs encoding the nucleocapsid. Our ribosome profiling analysis revealed that
ribosomes efficiently translate two novel CUG-initiated open reading frames
(ORFs), located within the so-called 5' untranslated region. We have termed the
resulting proteins U1 and U2. Comparative genomic analysis confirmed that these
ORFs are conserved across all available torovirus sequences, and the inferred
amino acid sequences are subject to purifying selection, indicating that U1 and
U2 are functionally relevant. This study provides the first high-resolution
analysis of transcription and translation in this neglected group of livestock
pathogens.IMPORTANCE Toroviruses infect cattle, goats, pigs, and horses worldwide
and can cause gastrointestinal disease. There is no treatment or vaccine, and
their ability to spill over into humans has not been assessed. These viruses are
related to important human pathogens, including severe acute respiratory syndrome
(SARS) coronavirus, and they share some common features; however, the mechanism
that they use to produce sgRNA molecules differs. Here, we performed deep
sequencing to determine how equine torovirus produces sgRNAs. In doing so, we
also identified two previously unknown open reading frames "hidden" within the
genome. Together these results highlight the similarities and differences between
this domestic animal virus and related pathogens of humans and livestock.
PMID- 29950410
TI - CD8+ T-Cell Response-Associated Evolution of Hepatitis B Virus Core Protein and
Disease Progress.
AB - Under the immune pressure of cytotoxic T cells (CTLs), hepatitis B virus (HBV)
evolves to accumulate mutations more likely within epitopes to evade immune
detection. However, little is known about the specific patterns of the immune
pressure-associated HBV mutation of T-cell epitopes and their link to disease
progression. Here, we observed a correlation of the accumulated variants on HBV
core protein (HBc) with the disease severity of HBV infection. Further analysis
indicated that these substitutions were mostly located within CD8+ T-cell
epitopes of HBc protein, which were systematically screened and identified in an
unbiased manner in our study. From individual peptide level to the human
leukocyte antigen I (HLA-I)-restricted population level, we elucidated that the
mutations in these well-defined HLA-I-restricted T-cell epitopes significantly
decreased antiviral activity-specific CTLs and were positively associated with
clinical parameters and disease progression in HBV-infected patients. The
molecular pattern for viral epitope variations based on the sequencing of 105 HBV
virus genomes indicated that the C-terminal portion (Pc), especially the Pc-1 and
Pc-2 positions, have the highest mutation rates. Further structural analysis of
HLA-A*02 complexed to diverse CD8+ T-cell epitopes revealed that the highly
variable C-terminal bulged peak of M-shaped HBc-derived epitopes are solvent
exposed, and most of the CDR3betas of the T-cell receptor hover over them. These
data shed light on the molecular and immunological mechanisms of T-cell immunity
associated viral evolution in hepatitis B progression, which is beneficial for
designing immunotherapies and vaccines.IMPORTANCE The specific patterns of
sequence polymorphisms of T-cell epitopes and the immune mechanisms of the HBV
epitope mutation-linked disease progression are largely unclear. In this study,
we systematically evaluated the contribution of CD8+ T cells to the disease
progress-associated evolution of HBV. By evaluation of patient T-cell responses
based on the peptide repertoire, we comprehensively characterized the association
of clinical parameters in chronic hepatitis B with the antiviral T-cell response
associated mutations of the viruses from the single-epitope level to the overall
HLA-I-restricted peptide levels. Furthermore, we investigated the molecular basis
of the HLA-A2-restricted peptide immune escape and found that the solvent-exposed
C-terminal portion of the epitopes is highly variable under CDR3beta recognition.
Our work may provide a comprehensive evaluation of viral mutations impacted by
the host CTL response in HBV disease progression in the context of the full
repertoire of HBc-derived epitopes.
PMID- 29950411
TI - Human MxB Protein Is a Pan-herpesvirus Restriction Factor.
AB - Herpesvirus infections are highly prevalent in the human population and persist
for life. They are often acquired subclinically but potentially progress to life
threatening diseases in immunocompromised individuals. The interferon system is
indispensable for the control of herpesviral replication. However, the
responsible antiviral effector mechanisms are not well characterized. The type I
interferon-induced, human myxovirus resistance 2 (MX2) gene product MxB, a
dynamin-like large GTPase, has recently been identified as a potent inhibitor of
HIV-1. We now show that MxB also interferes with an early step of herpesvirus
replication, affecting alpha-, beta-, and gammaherpesviruses before or at the
time of immediate early gene expression. Defined MxB mutants influencing GTP
binding and hydrolysis revealed that the effector mechanism against herpesviruses
is thoroughly different from that against HIV-1. Overall, our findings
demonstrate that MxB serves as a broadly acting intracellular restriction factor
that controls the establishment of not only retrovirus but also herpesvirus
infection of all three subfamilies.IMPORTANCE Human herpesviruses pose a constant
threat to human health. Reactivation of persisting herpesvirus infections,
particularly in immunocompromised individuals and the elderly, can cause severe
diseases, such as zoster, pneumonia, encephalitis, or cancer. The interferon
system is relevant for the control of herpesvirus replication as exemplified by
fatal disease outcomes in patients with primary immunodeficiencies. Here, we
describe the interferon-induced, human MX2 gene product MxB as an efficient
restriction factor of alpha-, beta-, and gammaherpesviruses. MxB has previously
been described as an inhibitor of HIV-1. Importantly, our mutational analyses of
MxB reveal an antiviral mechanism of herpesvirus restriction distinct from that
against HIV-1. Thus, the dynamin-like MxB GTPase serves as a broadly acting
intracellular restriction factor that controls retrovirus as well as herpesvirus
infections.
PMID- 29950412
TI - The Human Cytomegalovirus Protein UL148A Downregulates the NK Cell-Activating
Ligand MICA To Avoid NK Cell Attack.
AB - Natural killer (NK) cells are lymphocytes of the innate immune system capable of
killing hazardous cells, including virally infected cells. NK cell-mediated
killing is triggered by activating receptors. Prominent among these is the
activating receptor NKG2D, which binds several stress-induced ligands, among them
major histocompatibility complex (MHC) class I-related chain A (MICA). Most of
the human population is persistently infected with human cytomegalovirus (HCMV),
a virus which employs multiple immune evasion mechanisms, many of which target NK
cell responses. HCMV infection is mostly asymptomatic, but in congenitally
infected neonates and in immunosuppressed patients it can lead to serious
complications and mortality. Here we discovered that an HCMV protein named UL148A
whose role was hitherto unknown is required for evasion of NK cells. We
demonstrate that UL148A-deficient HCMV strains are impaired in their ability to
downregulate MICA expression. We further show that when expressed by itself,
UL148A is not sufficient for MICA targeting, but rather acts in concert with an
unknown viral factor. Using inhibitors of different cellular degradation
pathways, we show that UL148A targets MICA for lysosomal degradation. Finally, we
show that UL148A-mediated MICA downregulation hampers NK cell-mediated killing of
HCMV-infected cells. Discovering the full repertoire of HCMV immune evasion
mechanisms will lead to a better understanding of the ability of HCMV to persist
in the host and may also promote the development of new vaccines and drugs
against HCMV.IMPORTANCE Human cytomegalovirus (HCMV) is a ubiquitous pathogen
which is usually asymptomatic but that can cause serious complications and
mortality in congenital infections and in immunosuppressed patients. One of the
difficulties in developing novel vaccines and treatments for HCMV is its
remarkable ability to evade our immune system. In particular, HCMV directs
significant efforts to thwarting cells of the innate immune system known as
natural killer (NK) cells. These cells are crucial for successful control of HCMV
infection, and yet our understanding of the mechanisms which HCMV utilizes to
elude NK cells is partial at best. In the present study, we discovered that a
protein encoded by HCMV which had no known function is important for preventing
NK cells from killing HCMV-infected cells. This knowledge can be used in the
future for designing more-efficient HCMV vaccines and for formulating novel
therapies targeting this virus.
PMID- 29950413
TI - Human Cytomegalovirus Immediate Early 1 Protein Causes Loss of SOX2 from Neural
Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus.
AB - The mechanisms underlying neurodevelopmental damage caused by virus infections
remain poorly defined. Congenital human cytomegalovirus (HCMV) infection is the
leading cause of fetal brain development disorders. Previous work has linked HCMV
infection to perturbations of neural cell fate, including premature
differentiation of neural progenitor cells (NPCs). Here, we show that HCMV
infection of NPCs results in loss of the SOX2 protein, a key pluripotency
associated transcription factor. SOX2 depletion maps to the HCMV major immediate
early (IE) transcription unit and is individually mediated by the IE1 and IE2
proteins. IE1 causes SOX2 downregulation by promoting the nuclear accumulation
and inhibiting the phosphorylation of STAT3, a transcriptional activator of SOX2
expression. Deranged signaling resulting in depletion of a critical stem cell
protein is an unanticipated mechanism by which the viral major IE proteins may
contribute to brain development disorders caused by congenital HCMV
infection.IMPORTANCE Human cytomegalovirus (HCMV) infections are a leading cause
of brain damage, hearing loss, and other neurological disabilities in children.
We report that the HCMV proteins known as IE1 and IE2 target expression of human
SOX2, a central pluripotency-associated transcription factor that governs neural
progenitor cell (NPC) fate and is required for normal brain development. Both
during HCMV infection and when expressed alone, IE1 causes the loss of SOX2 from
NPCs. IE1 mediates SOX2 depletion by targeting STAT3, a critical upstream
regulator of SOX2 expression. Our findings reveal an unanticipated mechanism by
which a common virus may cause damage to the developing nervous system and
suggest novel targets for medical intervention.
PMID- 29950414
TI - Transgene-Assisted Genetic Screen Identifies rsd-6 and Novel Genes as Key
Components of Antiviral RNA Interference in Caenorhabditis elegans.
AB - RNA interference (RNAi) is a widespread antiviral mechanism triggered by virus
produced double-stranded RNAs (dsRNAs). In Caenorhabditis elegans, antiviral RNAi
involves a RIG-I-like RNA helicase, termed DRH-1 (dicer related RNA helicase 1),
that is not required for classical RNAi triggered by artificial dsRNA. Currently,
whether antiviral RNAi in C. elegans involves novel factors that are dispensable
for classical RNAi remains an open question. To address this question, we
designed and carried out a genetic screen that aims to identify novel genes
involved in worm antiviral RNAi. By introducing extra copies of known antiviral
RNAi genes into the reporter worms, we managed to reject alleles derived from 4
known antiviral RNAi genes, including the DRH-1 coding gene, during the screen.
Our genetic screen altogether identified 25 alleles, which were assigned to 11
candidate genes and 2 known antiviral RNAi genes through genetic complementation
tests. Using a mapping-by-sequencing strategy, we identified one of the candidate
genes as rsd-6, a gene that helps maintain genome integrity through an endogenous
gene-silencing pathway but was not known to be required for antiviral RNAi. More
importantly, we found that two of the candidate genes are required for antiviral
RNAi targeting Orsay virus, a natural viral pathogen of C. elegans, but
dispensable for classical RNAi. Since drh-1 is so far the only antiviral RNAi
gene not required for classical RNAi, we believe that our genetic screen led to
identification of novel worm genes that may target virus-specific features to
function in RNAi.IMPORTANCE In nematode worms, drh-1 detects virus-produced
double-stranded RNA (dsRNA), thereby specifically contributing to antiviral RNA
silencing. To identify drh-1-like genes with dedicated function in antiviral
RNAi, we recently carried out a genetic screen that was designed to automatically
reject all alleles derived from 4 known antiviral silencing genes, including drh
1 Of the 11 candidate genes identified, we found two of them to be required for
antiviral silencing targeting a natural viral pathogen of C. elegans but not for
classical RNA silencing triggered by artificial dsRNA. We believe that these two
genes are novel components of worm antiviral RNAi, considering the fact that drh
1 is the only known antiviral RNAi gene that is dispensable for classical RNAi.
This genetic screen also identified rsd-6, a gene that maintains genome integrity
under unfavorable conditions, as a key regulator of worm antiviral silencing,
demonstrating an interplay between antiviral immunity and genome integrity
maintenance.
PMID- 29950415
TI - Transmembrane Domains Mediate Intra- and Extracellular Trafficking of Epstein
Barr Virus Latent Membrane Protein 1.
AB - EBV latent membrane protein 1 (LMP1) is released from latently infected tumor
cells in small membrane-enclosed extracellular vesicles (EVs). Accumulating
evidence suggests that LMP1 is a major driver of EV content and functions. LMP1
modified EVs have been shown to influence recipient cell growth, migration,
differentiation, and regulation of immune cell function. Despite the significance
of LMP1-modified exosomes, very little is known about how this viral protein
enters or manipulates the host EV pathway. In this study, LMP1 deletion mutants
were generated to assess protein regions required for EV trafficking. Following
transfection of LMP1 or mutant plasmids, EVs were collected by differential
centrifugation, and the levels of specific cargo were evaluated by immunoblot
analysis. The results demonstrate that, together, the N terminus and
transmembrane region 1 of LMP1 are sufficient for efficient sorting into EVs.
Consistent with these findings, a mutant lacking the N terminus and transmembrane
domains 1 through 4 (TM5-6) failed to be packaged into EVs, and exhibited higher
colocalization with endoplasmic reticulum and early endosome markers than the
wild-type protein. Surprisingly, TM5-6 maintained the ability to colocalize and
form a complex with CD63, an abundant exosome protein that is important for the
incorporation of LMP1 into EVs. Other mutations within LMP1 resulted in enhanced
levels of secretion, pointing to potential positive and negative regulatory
mechanisms for extracellular vesicle sorting of LMP1. These data suggest new
functions of the N terminus and transmembrane domains in LMP1 intra- and
extracellular trafficking that are likely downstream of an interaction with
CD63.IMPORTANCE EBV infection contributes to the development of cancers, such as
nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin's disease, and posttransplant
lymphomas, in immunocompromised or genetically susceptible individuals. LMP1 is
an important viral protein expressed by EBV in these cancers. LMP1 is secreted in
extracellular vesicles (EVs), and the transfer of LMP1-modified EVs to uninfected
cells can alter their physiology. Understanding the cellular machinery
responsible for sorting LMP1 into EVs is limited, despite the importance of LMP1
modified EVs. Here, we illustrate the roles of different regions of LMP1 in EV
packaging. Our results show that the N terminus and TM1 are sufficient to drive
LMP1 EV trafficking. We further show the existence of potential positive and
negative regulatory mechanisms for LMP1 vesicle sorting. These findings provide a
better basis for future investigations to identify the mechanisms of LMP1
targeting to EVs, which could have broad implications in understanding EV cargo
sorting.
PMID- 29950416
TI - Aedes anphevirus (AeAV): an insect-specific virus distributed worldwide in Aedes
aegypti mosquitoes that has complex interplays with Wolbachia and dengue virus
infection in cells.
AB - Insect specific viruses (ISVs) of the yellow fever mosquito Aedes aegypti have
been demonstrated to modulate transmission of arboviruses such as dengue virus
(DENV) and West Nile virus by the mosquito. The diversity and composition of the
virome of Ae. aegypti, however, remains poorly understood. In this study, we
characterised Aedes anphevirus (AeAV), a negative-sense RNA virus from the order
Mononegavirales AeAV identified from Aedes cell lines were infectious to both Ae.
aegypti and Aedes albopictus cells, but not to three mammalian cell lines. To
understand the incidence and genetic diversity of AeAV, we assembled 17 coding
complete and two partial genomes of AeAV from available RNA-Seq data. AeAV
appears to transmit vertically and be present in laboratory colonies, wild-caught
mosquitoes and cell lines worldwide. Phylogenetic analysis of AeAV strains
indicates that as the Ae. aegypti mosquito has expanded into the Americas and
Asia-Pacific, AeAV has evolved into monophyletic African, American and Asia
Pacific lineages. The endosymbiotic bacterium Wolbachia pipientis restricts
positive-sense RNA viruses in Ae. aegypti Re-analysis of a small RNA library of
Ae. aegypti cells co-infected with AeAV and Wolbachia produces an abundant RNAi
response consistent with persistent virus replication. We found Wolbachia
enhances replication of AeAV when compared to a tetracycline cleared cell line,
and AeAV modestly reduces DENV replication in vitro The results from our study
improve understanding of the diversity and evolution of the virome of Ae. aegypti
and adds to previous evidence that shows Wolbachia does not restrict a range of
negative strand RNA viruses.IMPORTANCE The mosquito Aedes aegypti transmits a
number of arthropod-borne viruses (arboviruses) such as dengue virus and Zika
virus. Mosquitoes also harbour insect-specific viruses that may affect
replication of pathogenic arboviruses in their body. Currently, however, there
are only a handful of insect-specific viruses described from Ae. aegypti in the
literature. Here, we characterise a novel negative strand virus, Aedes anphevirus
(AeAV). Meta-analysis of Ae. aegypti samples showed that it is present in Ae.
aegypti mosquitoes worldwide and is vertically transmitted. Wolbachia
transinfected mosquitoes are currently being used in biocontrol as they
effectively block transmission of several positive sense RNA viruses in
mosquitoes. Our results demonstrate that Wolbachia enhances the replication of
AeAV and modestly reduces dengue virus replication in a cell line model. This
study expands our understanding of the virome in Ae. aegypti as well as providing
insight into the complexity of the Wolbachia virus restriction phenotype.
PMID- 29950417
TI - Gallid Herpesvirus 1 Initiates Apoptosis in Uninfected Cells through Paracrine
Repression of p53.
AB - Apoptosis is a common innate defense mechanism of host cells against viral
infection and is therefore suppressed by many viruses, including herpes simplex
virus (HSV), via various strategies. A recent in vivo study reported the
apoptosis of remote uninfected cells during Gallid herpesvirus 1 (GaHV-1)
infection, yet little is known about this previously unknown aspect of
herpesvirus-host interactions. The aim of the present study was to investigate
the apoptosis of uninfected host cells during GaHV-1 infection. The present study
used in vitro and in ovo models, which avoided potential interference by host
antiviral immunity, and demonstrated that this GaHV-1-host interaction is
independent of host immune responses and important for both the pathological
effect of viral infection and early viral dissemination from the primary
infection site to distant tissues. Further, we revealed that GaHV-1 infection
triggers this process in a paracrine-regulated manner. Using genome-wide
transcriptome analyses in combination with a set of functional studies, we found
that this paracrine-regulated effect requires the repression of p53 activity in
uninfected cells. In contrast, the activation of p53 not only prevented the
apoptosis of remote uninfected cells and subsequent pathological damage induced
by GaHV-1 infection but also delayed viral dissemination significantly. Moreover,
p53 activation repressed viral replication both in vitro and in ovo, suggesting
that dual cell-intrinsic mechanisms underlie the suppression of GaHV-1 infection
by p53 activation. This study uncovers the mechanism underlying the herpesvirus
triggered apoptosis of remote host cells and extends our understanding of both
herpesvirus-host interactions and the roles of p53 in viral infection.IMPORTANCE
It is well accepted that herpesviruses suppress the apoptosis of host cells via
various strategies to ensure sustained viral replication during infection.
However, a recent in vivo study reported the apoptosis of remote uninfected cells
during GaHV-1 infection. The mechanism and the biological meaning of this
unexpected herpesvirus-host interaction are unclear. This study uncovers the
mechanisms of herpesvirus-triggered apoptosis in uninfected cells and may also
contribute to a mechanistic illustration of paracrine-regulated apoptosis induced
by other viruses in uninfected host cells.
PMID- 29950418
TI - Tomato Yellow Leaf Curl Virus V2 Interacts with Host Histone Deacetylase 6 To
Suppress Methylation-Mediated Transcriptional Gene Silencing in Plants.
AB - Cytosine DNA methylation is a conserved epigenetic silencing mechanism that
defends against biotic stresses such as geminivirus infection. As a
countermeasure, geminiviruses encode proteins that inhibit methylation and
transcriptional gene silencing (TGS). Previous studies showed that V2 protein of
Tomato yellow leaf curl virus (TYLCV) functions as a TGS suppressor. However, how
V2 mediates TGS suppression remains unknown. Here we show that V2 interacts
directly with a Nicotiana benthamiana histone deacetylase 6 (NbHDA6), a homolog
of Arabidopsis HDA6 (AtHDA6), known to be involved in gene silencing in
cooperation with methyltransferase 1 (MET1). NbHDA6 genetically complemented a
late-flowering phenotype and restored histone deacetylation of an AtHDA6 mutant.
Furthermore, our investigation showed that NbHDA6 displayed histone deacetylase
enzymatic activity, which was not inhibited by V2. Genetic analysis revealed that
silencing of NbHDA6 expression resulted in enhanced susceptibility to TYLCV
infection. In addition, methylation-sensitive PCR and bisulfite sequencing
analysis showed that silencing of NbHDA6 expression caused reduced DNA
methylation of the viral genome in infected plants. HDA6 was previously shown to
recruit and physically interact with MET1 to function in gene silencing. Using
competitive pulldown and coimmunoprecipitation assays, we demonstrated that V2
did not interact but competed with NbMET1 for direct binding to NbHDA6. These
findings suggest that V2 interacts with host HDA6 and interferes with the
recruitment of MET1 by HDA6, resulting in decreased methylation of the viral DNA
genome by TGS with a concomitant increase in host susceptibility to TYLCV
infection.IMPORTANCE Plants employ repressive viral genome methylation as an
epigenetic defense against geminiviruses. In turn, geminiviruses encode proteins
that inhibit methylation by TGS. Previous studies showed that TYLCV V2 can
efficiently suppress TGS, but the mechanism remains unknown. We showed that V2
interacted with NbHDA6 but did not inhibit its enzymatic activity. As HDA6 is
known to be involved in gene silencing in cooperation with MET1, we explored the
relationship between V2, NbMET1, and NbHDA6. Our investigation showed that V2 did
not interact but competed with NbMET1 for direct binding to NbHDA6. To our
knowledge, this is the first report that viral proteins inhibit TGS by
interacting with histone deacetylase but not by blocking the methyl cycle. This
work provides an additional mechanism for TGS suppression by geminiviruses.
PMID- 29950419
TI - Rubella Viruses Shift Cellular Bioenergetics to a More Oxidative and Glycolytic
Phenotype with a Strain-Specific Requirement for Glutamine.
AB - The flexible regulation of cellular metabolic pathways enables cellular
adaptation to changes in energy demand under conditions of stress such as posed
by a virus infection. To analyze such an impact on cellular metabolism, rubella
virus (RV) was used in this study. RV replication under selected substrate
supplementation with glucose, pyruvate, and glutamine as essential nutrients for
mammalian cells revealed its requirement for glutamine. The assessment of the
mitochondrial respiratory (based on the oxygen consumption rate) and glycolytic
(based on the extracellular acidification rate) rate and capacity by respective
stress tests through Seahorse technology enabled determination of the
bioenergetic phenotype of RV-infected cells. Irrespective of the cellular
metabolic background, RV infection induced a shift of the bioenergetic state of
epithelial cells (Vero and A549) and human umbilical vein endothelial cells to a
higher oxidative and glycolytic level. Interestingly there was a RV strain
specific, but genotype-independent demand for glutamine to induce a significant
increase in metabolic activity. While glutaminolysis appeared to be rather
negligible for RV replication, glutamine could serve as donor of its amide
nitrogen in biosynthesis pathways for important metabolites. This study suggests
that the capacity of RVs to induce metabolic alterations could evolve differently
during natural infection. Thus, changes in cellular bioenergetics represent an
important component of virus-host interactions and could complement our
understanding of the viral preference for a distinct host cell
population.IMPORTANCE RV pathologies, especially during embryonal development,
could be connected with its impact on mitochondrial metabolism. With bioenergetic
phenotyping we pursued a rather novel approach in virology. For the first time it
was shown that a virus infection could shift the bioenergetics of its infected
host cell to a higher energetic state. Notably, the capacity to induce such
alterations varied among different RV isolates. Thus, our data add viral
adaptation of cellular metabolic activity to its specific needs as a novel aspect
to virus-host evolution. In addition, this study emphasizes the implementation of
different viral strains in the study of virus-host interactions and the use of
bioenergetic phenotyping of infected cells as a biomarker for virus-induced
pathological alterations.
PMID- 29950420
TI - 25-Hydroxycholesterol Production by the Cholesterol-25-Hydroxylase Interferon
Stimulated Gene Restricts Mammalian Reovirus Infection.
AB - Following the initial detection of viral infection, innate immune responses
trigger the induction of numerous interferon-stimulated genes (ISGs) to inhibit
virus replication and dissemination. One such ISG encodes cholesterol-25
hydroxylase (CH25H), an enzyme that catalyzes the oxidation of cholesterol to
form a soluble product, 25-hydroxycholesterol (25HC). Recent studies have found
that CH25H is broadly antiviral; it inhibits infection by several viruses. For
enveloped viruses, 25HC inhibits membrane fusion, likely by altering membrane
characteristics such as hydrophobicity or cholesterol aggregation. However, the
mechanisms by which 25HC restricts infection of nonenveloped viruses are unknown.
We examined whether 25HC restricts infection by mammalian reovirus. Treatment
with 25HC restricted infection by reovirus prototype strains type 1 Lang and type
3 Dearing. In contrast to reovirus virions, 25HC did not restrict infection by
reovirus infectious subvirion particles (ISVPs), which can penetrate either
directly at the cell surface or in early endosomal membranes. Treatment with 25HC
altered trafficking of reovirus particles to late endosomes and delayed the
kinetics of reovirus uncoating. These results suggest that 25HC inhibits the
efficiency of cellular entry of reovirus virions, which may require specific
endosomal membrane dynamics for efficient membrane penetration.IMPORTANCE The
innate immune system is crucial for effective responses to viral infection. Type
I interferons, central components of innate immunity, induce expression of
hundreds of ISGs; however, the mechanisms of action of these antiviral proteins
are not well understood. CH25H, encoded by an ISG, represents a significant
constituent of these cellular antiviral strategies, as its metabolic product,
25HC, can act in both an autocrine and a paracrine fashion to protect cells from
infection and has been shown to limit viral infection in animal models. Further
investigation into the mechanism of action of 25HC may inform novel antiviral
therapies and influence the use of mammalian reovirus in clinical trials as an
oncolytic agent.
PMID- 29950422
TI - The 135 Gene of Goatpox Virus Encodes an Inhibitor of NF-kappaB and Apoptosis and
May Serve as an Improved Insertion Site To Generate Vectored Live Vaccine.
AB - Goatpox virus (GTPV) is an important member of the Capripoxvirus genus of the
Poxviridae Capripoxviruses have large and complex DNA genomes encoding many
unknown proteins that may contribute to virulence. We identified that the 135
open reading frame of GTPV is an early gene that encodes an ~18-kDa protein that
is nonessential for viral replication in cells. This protein functioned as an
inhibitor of NF-kappaB activation and apoptosis and is similar to the N1L protein
of vaccinia virus. In the natural host, sheep, deletion of the 135 gene from the
GTPV live vaccine strain AV41 resulted in less attenuation than that induced by
deletion of the tk gene, a well-defined nonessential gene in the poxvirus genome.
Using the 135 gene as the insertion site, a recombinant AV41 strain expressing
hemagglutinin of peste des petits ruminants virus (PPRV) was generated and
elicited stronger neutralization antibody responses than those obtained using the
traditional tk gene as the insertion site. These results suggest that the 135
gene of GTPV encodes an immunomodulatory protein to suppress host innate immunity
and may serve as an optimized insertion site to generate capripoxvirus-vectored
live dual vaccines.IMPORTANCE Capripoxviruses are etiological agents of important
diseases in sheep, goats, and cattle. There are rare reports about viral protein
function related to capripoxviruses. In the present study, we found that the 135
protein of GTPV plays an important role in inhibition of innate immunity and
apoptosis in host cells. Use of the 135 gene as the insertion site to generate a
vectored vaccine resulted in stronger adaptive immune responses than those
obtained using the tk locus as the insertion site. As capripoxviruses are
promising virus-vectored vaccines against many important diseases in small
ruminants and cattle, the 135 gene may serve as an improved insertion site to
generate recombinant capripoxvirus-vectored live dual vaccines.
PMID- 29950421
TI - A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS
CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and
Protective Efficacy against MERS-CoV.
AB - The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV)
continues to infect humans and camels, calling for efficient, cost-effective, and
broad-spectrum strategies to control its spread. Nanobodies (Nbs) are single
domain antibodies derived from camelids and sharks and are potentially cost
effective antivirals with small size and great expression yield. In this study,
we developed a novel neutralizing Nb (NbMS10) and its human-Fc-fused version
(NbMS10-Fc), both of which target the MERS-CoV spike protein receptor-binding
domain (RBD). We further tested their receptor-binding affinity, recognizing
epitopes, cross-neutralizing activity, half-life, and efficacy against MERS-CoV
infection. Both Nbs can be expressed in yeasts with high yield, bind to MERS-CoV
RBD with high affinity, and block the binding of MERS-CoV RBD to the MERS-CoV
receptor. The binding site of the Nbs on the RBD was mapped to be around residue
Asp539, which is part of a conserved conformational epitope at the receptor
binding interface. NbMS10 and NbMS10-Fc maintained strong cross-neutralizing
activity against divergent MERS-CoV strains isolated from humans and camels.
Particularly, NbMS10-Fc had significantly extended half-life in vivo; a single
dose treatment of NbMS10-Fc exhibited high prophylactic and therapeutic efficacy
by completely protecting humanized mice from lethal MERS-CoV challenge. Overall,
this study proves the feasibility of producing cost-effective, potent, and broad
spectrum Nbs against MERS-CoV and has produced Nbs with great potentials as anti
MERS-CoV therapeutics.IMPORTANCE Therapeutic development is critical for
preventing and treating continual MERS-CoV infections in humans and camels.
Because of their small size, nanobodies (Nbs) have advantages as antiviral
therapeutics (e.g., high expression yield and robustness for storage and
transportation) and also potential limitations (e.g., low antigen-binding
affinity and fast renal clearance). Here, we have developed novel Nbs that
specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein.
They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's
binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the
in vivo half-life of the Nbs is significantly extended. Moreover, the Nbs can
potently cross-neutralize the infections of diverse MERS-CoV strains isolated
from humans and camels. The Fc-tagged Nb also completely protects humanized mice
from lethal MERS-CoV challenge. Taken together, our study has discovered novel
Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV
therapeutic agents.
PMID- 29950423
TI - HIV-1 Subtype C-Infected Children with Exceptional Neutralization Breadth Exhibit
Polyclonal Responses Targeting Known Epitopes.
AB - We have previously shown that HIV-1-infected children develop broader and more
potent neutralizing antibody responses than adults. This study aimed to determine
the antibody specificities in 16 HIV-1 subtype C-infected children who displayed
exceptional neutralization breadth on a 22-multisubtype virus panel. All children
were antiretroviral treatment (ART) naive with normal CD4 counts despite being
infected for a median of 10.1 years with high viral loads. The specificity of
broadly neutralizing antibodies (bNAbs) was determined using epitope-ablating
mutants, chimeric constructs, and depletion or inhibition of activity with
peptides and glycoproteins. We found that bNAbs in children largely targeted
previously defined epitopes, including the V2-glycan, V3-glycan, CD4bs, and gp120
gp41 interface. Remarkably, 63% of children had antibodies targeting 2 or 3 and,
in one case, 4 of these bNAb epitopes. Longitudinal analysis of plasma from a
mother-child pair over 9 years showed that while they both had similar
neutralization profiles, the antibody specificities differed. The mother
developed antibodies targeting the V2-glycan and CD4bs, whereas bNAb
specificities in the child could not be mapped until 6 years, when a minor V2
glycan response appeared. The child also developed high-titer membrane-proximal
external region (MPER) binding antibodies not seen in the mother, although these
were not a major bNAb specificity. Overall, exceptional neutralization breadth in
this group of children may be the result of extended exposure to high antigenic
load in the context of an intact immune system, which allowed for the activation
of multiple B cell lineages and the generation of polyclonal responses targeting
several bNAb epitopes.IMPORTANCE An HIV vaccine is likely to require bNAbs, which
have been shown to prevent HIV acquisition in nonhuman primates. Recent evidence
suggests that HIV-infected children are inherently better at generating bNAbs
than adults. Here, we show that exceptional neutralization breadth in a group of
viremic HIV-1 subtype C-infected children was due to the presence of polyclonal
bNAb responses. These bNAbs targeted multiple epitopes on the HIV envelope
glycoprotein previously defined in adult infection, suggesting that the immature
immune system recognizes HIV antigens similarly. Since elicitation of a
polyclonal bNAb response is the basis of next-generation HIV envelope vaccines,
further studies of how bNAb lineages are stimulated in children is warranted.
Furthermore, our findings suggest that children may respond particularly well to
vaccines designed to elicit antibodies to multiple bNAb epitopes.
PMID- 29950424
TI - Geminivirus Replication protein impairs SUMO conjugation of PCNA at two acceptor
sites.
AB - Geminiviruses are DNA viruses that replicate in nuclei of infected plant cells
using the plant DNA replication machinery, including PCNA (Proliferating cellular
nuclear antigen), a cofactor that orchestrates genome duplication and maintenance
by recruiting crucial players to replication forks. These viruses encode a
multifunctional protein, Rep, which is essential for viral replication, induces
the accumulation of the host replication machinery and interacts with several
host proteins, including PCNA and the SUMO E2 conjugation enzyme (SCE1). Post
translational modification of PCNA by ubiquitin or SUMO plays an essential role
in the switching of PCNA between interacting partners during DNA metabolism
processes (e.g. replication, recombination, repair, etc.). In yeast, PCNA
sumoylation has been associated to DNA repair involving homologous recombination
(HR). Previously, we reported that ectopic Rep expression results in very
specific changes in the sumoylation pattern of plant cells. In this work, we
show, using a reconstituted sumoylation system in Escherichia coli, that tomato
PCNA is sumoylated at two residues, K254 and K164, and that co-expression of the
geminivirus protein Rep suppresses sumoylation at these lysines. Finally, we
confirm that PCNA is sumoylated in planta and that Rep also interferes with PCNA
sumoylation in plant cells.IMPORTANCESUMO adducts have a key role in regulating
the activity of animal and yeast PCNA on DNA repair and replication. Our work
demonstrates for the first time that sumoylation of plant PCNA occurs in plant
cells and that a plant virus interferes with this modification. This work marks
the importance of sumoylation in allowing viral infection and replication in
plants. Moreover, it constitutes a prime example of how viral proteins
interfering with post-translational modifications of selected host factors to
create a proper environment for infection.
PMID- 29950425
TI - Kaposi's Sarcoma-Associated Herpesvirus Nonstructural Membrane Protein pK15
Recruits the Class II Phosphatidylinositol 3-Kinase PI3K-C2alpha To Activate
Productive Viral Replication.
AB - Kaposi's sarcoma (KS)-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8)
causes the angiogenic tumor KS and two B-cell malignancies. The KSHV
nonstructural membrane protein encoded by the open reading frame (ORF) K15
recruits and activates several cellular proteins, including phospholipase Cgamma1
(PLCgamma1), components of the NF-kappaB pathway, as well as members of the Src
family of nonreceptor tyrosine kinases, and thereby plays an important role in
the activation of angiogenic and inflammatory pathways that contribute to the
pathogenesis of KS as well as KSHV productive (lytic) replication. In order to
identify novel cellular components involved in the biology of pK15, we
immunoprecipitated pK15 from KSHV-infected endothelial cells and identified
associated proteins by label-free quantitative mass spectrometry. Cellular
proteins interacting with pK15 point to previously unappreciated cellular
processes, such as the endocytic pathway, that could be involved in the function
of pK15. We found that the class II phosphatidylinositol 3-kinase (PI3K) PI3K
C2alpha, which is involved in the endocytosis of activated receptor tyrosine
kinases and their signaling from intracellular organelles, interacts and
colocalizes with pK15 in vesicular structures abundant in the perinuclear area.
Further functional analysis revealed that PI3K-C2alpha contributes to the pK15
dependent phosphorylation of PLCgamma1 and Erk1/2. PI3K-C2alpha also plays a role
in KSHV lytic replication, as evidenced by the reduced expression of the viral
lytic genes K-bZIP and ORF45 as well as the reduced release of infectious virus
in PI3K-C2alpha-depleted KSHV-infected endothelial cells. Taken together, our
results suggest a role of the cellular PI3K-C2alpha protein in the functional
properties of the KSHV pK15 protein.IMPORTANCE The nonstructural membrane protein
encoded by open reading frame K15 of Kaposi's sarcoma-associated herpesvirus
(KSHV) (HHV8) activates several intracellular signaling pathways that contribute
to the angiogenic properties of KSHV in endothelial cells and to its reactivation
from latency. A detailed understanding of how pK15 activates these intracellular
signaling pathways is a prerequisite for targeting these processes specifically
in KSHV-infected cells. By identifying pK15-associated cellular proteins using a
combination of immunoprecipitation and mass spectrometry, we provide evidence
that pK15-dependent signaling may occur from intracellular vesicles and rely on
the endocytotic machinery. Specifically, a class II PI3K, PI3K-C2alpha, is
recruited by pK15 and involved in pK15-dependent intracellular signaling and
viral reactivation from latency. These findings are of importance for future
intervention strategies that aim to disrupt the activation of intracellular
signaling by pK15 in order to antagonize KSHV productive replication and
tumorigenesis.
PMID- 29950426
TI - Modified Anoikis Assay That Functionally Segregates Epstein-Barr Virus LMP1
Strains into Two Groups.
AB - Nasopharyngeal carcinoma (NPC) is a metastatic Epstein-Barr virus (EBV)
associated cancer that expresses the viral oncogenic protein, latent membrane
protein 1 (LMP1). During epithelial metastasis, detached cells must overcome
anoikis-induced cell death and gain the ability to reattach and restore growth
potential. Anoikis assays have revealed cell survival mechanisms during
suspension, but few studies have tracked the fate of cells surviving anoikis
inducing conditions. In this study, a modified anoikis assay was used to examine
if the expression of LMP1 confers the recovery of epithelial cells from anoikis.
Cells expressing LMP1 mutants and strains were evaluated for distinguishing
properties in survival during suspension, reattachment, and outgrowth potential.
Expression of LMP1 promoted the outgrowth of the NPC cell line HK1 following
anoikis induction that was not attributed to enhanced cell survival in suspension
or reattachment. The mechanism of LMP1-induced outgrowth required Akt signaling
and the conserved PXQXT motif on LMP1, which activates Akt. Deletion of any of
the three LMP1 C-terminal activation regions (CTAR) abrogated anoikis recovery,
suggesting that additional LMP1-regulated signaling pathways are likely involved.
Of the seven LMP1 strains, only B958, China1, and Med+ promoted HK1 outgrowth
from anoikis. This distinguishing biological property segregates LMP1 strains
into two categories (anoikis recovering and nonrecovering) and suggests that LMP1
strain-specific sequences may be important in determining metastatic outgrowth
potential in NPC tumors.IMPORTANCE LMP1 is one of the most divergent sequences in
the EBV genome and phylogenetically segregates into seven LMP1 strains. The LMP1
strains differ in geographical distribution and NPC tumor prevalence, but the
molecular basis for this potential selection is not clear. While there are
signaling motifs conserved in all LMP1 sequences from circulating EBV isolates,
phylogenetic studies of NPC also suggest that there may be sequence selection for
tumor-associated LMP1 strains and polymorphisms. The present study describes a
modified anoikis assay that can distinguish LMP1 strains into two groups by
biological properties. The pleiotropic LMP1 signaling properties and sequence
diversity may offer a unique opportunity to illuminate the complex mechanisms of
metastasis. Although the host genomic landscape is variable between NPC tumors,
the present functional-mapping studies on LMP1 support the notion that viral
proteins could serve as molecular tool kits and potentially reveal sequence
associated risk factors in NPC metastatic progression.
PMID- 29950427
TI - LIN-12/Notch Regulates GABA Signaling at the Caenorhabditis elegans Neuromuscular
Junction.
AB - The role of Notch signaling in cell-fate decisions has been studied extensively;
however, this pathway is also active in adult tissues, including the nervous
system. Notch signaling modulates a wide range of behaviors and processes of the
nervous system in the nematode Caenorhabditis elegans, but there is no evidence
for Notch signaling directly altering synaptic strength. Here, we demonstrate
Notch-mediated regulation of synaptic activity at the C. elegans neuromuscular
junction (NMJ). For this, we used aldicarb, an inhibitor of the enzyme
acetylcholinesterase, and assessed paralysis rates of animals with altered Notch
signaling. Notch receptors LIN-12 and GLP-1 are required for normal NMJ function;
they regulate NMJ activity in an opposing fashion. Complete loss of LIN-12 skews
the excitation/inhibition balance at the NMJ toward increased activity, whereas
partial loss of GLP-1 has the opposite effect. Specific Notch ligands and co
ligands are also required for proper NMJ function. The role of LIN-12 is
independent of cell-fate decisions; manipulation of LIN-12 signaling through RNAi
knockdown or overexpression of the co-ligand OSM-11 after development alters NMJ
activity. We demonstrate that LIN-12 modulates GABA signaling in this paradigm,
as loss of GABA signaling suppresses LIN-12 gain-of-function defects. Further
analysis, in vivo and in silico, suggests that LIN-12 may modulate transcription
of the GABAB receptor GBB-2 Our findings confirm a non-developmental role for the
LIN-12/Notch receptor in regulating synaptic signaling and identify the GABAB
receptor GBB-2 as a potential Notch transcriptional target in the C. elegans
nervous system.
PMID- 29950428
TI - The Effect of Balancing Selection on Population Differentiation: A Study with HLA
Genes.
AB - Balancing selection is defined as a class of selective regimes that maintain
polymorphism above what is expected under neutrality. Theory predicts that
balancing selection reduces population differentiation, as measured by FST.
However, balancing selection regimes in which different sets of alleles are
maintained in different populations could increase population differentiation. To
tackle the connection between balancing selection and population differentiation,
we investigated population differentiation at the HLA genes, which constitute the
most striking example of balancing selection in humans. We found that population
differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on
average lower than that of SNPs in other genomic regions. We show that these
results require using a computation that accounts for the dependence of FST on
allele frequencies. However, in pairs of closely related populations, where
genome-wide differentiation is low, differentiation at HLA is higher than in
other genomic regions. Such increased population differentiation at HLA genes for
recently diverged population pairs was reproduced in simulations of overdominant
selection, as long as the fitness of the homozygotes differs between the
diverging populations. The results give insight into a possible "divergent
overdominance" mechanism for the nature of balancing selection on HLA genes
across human populations.
PMID- 29950429
TI - Insights into the Structure of the Spruce Budworm (Choristoneura fumiferana)
Genome, as Revealed by Molecular Cytogenetic Analyses and a High-Density Linkage
Map.
AB - Genome structure characterization can contribute to a better understanding of
processes such as adaptation, speciation, and karyotype evolution, and can
provide useful information for refining genome assemblies. We studied the genome
of an important North American boreal forest pest, the spruce budworm,
Choristoneura fumiferana, through a combination of molecular cytogenetic analyses
and construction of a high-density linkage map based on single nucleotide
polymorphism (SNP) markers obtained through a genotyping-by-sequencing (GBS)
approach. Cytogenetic analyses using fluorescence in situ hybridization methods
confirmed the haploid chromosome number of n = 30 in both sexes of C. fumiferana
and showed, for the first time, that this species has a WZ/ZZ sex chromosome
system. Synteny analysis based on a comparison of the Bombyx mori genome and the
C. fumiferana linkage map revealed the presence of a neo-Z chromosome in the
latter species, as previously reported for other tortricid moths. In this neo-Z
chromosome, we detected an ABC transporter C2 (ABCC2) gene that has been
associated with insecticide resistance. Sex-linkage of the ABCC2 gene provides a
genomic context favorable to selection and rapid spread of resistance against
Bacillus thuringiensis serotype kurstaki (Btk), the main insecticide used in
Canada to control spruce budworm populations. Ultimately, the linkage map we
developed, which comprises 3586 SNP markers distributed over 30 linkage groups
for a total length of 1720.41 cM, will be a valuable tool for refining our draft
assembly of the spruce budworm genome.
PMID- 29950430
TI - Targeted Chromosomal Rearrangements via Combinatorial Use of CRISPR/Cas9 and
Cre/LoxP Technologies in Caenorhabditis elegans.
AB - Rearranged chromosomes have been applied to construct genetic balancers to
manipulate essential genes in C. elegans Although much effort has been put into
constructing balancer chromosomes, approximately 6% (map units) of the C. elegans
genome has not been covered, and this area lies mostly in pairing centers (PCs).
Here, we developed a method for conditional chromosomal engineering through
combinatorial use of the CRISPR/Cas9 and Cre/LoxP technologies. Functional DNA
fragments containing LoxP sequences were inserted into designated genomic loci
using a modified counterselection (cs)-CRISPR method. Then, heat-shock-induced
Cre recombinase induced an inversion of the chromosomal region between the two
LoxP sites. The chromosomal inversions were subsequently detected by the
appearance of pharyngeal GFP. Through this method, we have successfully generated
several chromosomal inversion lines, providing valuable resources for studying
essential genes in pairing centers.
PMID- 29950431
TI - Generation and Phenotype Identification of PAX4 Gene Knockout Rabbit by
CRISPR/Cas9 System.
AB - Paired-homeodomain transcription factor 4 (PAX4) gene encodes a transcription
factor which plays an important role in the generation, differentiation,
development, and survival of insulin-producing beta-cells during mammalian
pancreas development. PAX4 is a key diabetes mellitus (DM) susceptibility gene,
which is associated with many different types of DM, including T1DM, T2DM,
maturity onset diabetes of the young 9 (MODY9) and ketosis prone diabetes. In
this study, a novel PAX4 gene knockout (KO) model was generated through co
injection of clustered regularly interspaced short palindromic repeats (CRISPR)
associated protein 9 (Cas9) mRNA/sgRNA into rabbit zygotes. Typical phenotypes of
growth retardation, persistent hyperglycemia, decreased number of insulin
producing beta cells and increased number of glucagon-producing alpha cells were
observed in the homozygous PAX4 KO rabbits. Furthermore, DM associated phenotypes
including diabetic nephropathy, hepatopathy, myopathy and cardiomyopathy were
also observed in the homozygous PAX4 KO rabbits but not in the wild type (WT)
controls and the heterozygous PAX4 KO rabbits. In summary, this is the first PAX4
gene KO rabbit model generated by CRISPR/Cas9 system. This novel rabbit model may
provide a new platform for function study of PAX4 gene in rabbit and gene therapy
of human DM in clinical trails.
PMID- 29950432
TI - Flu vaccines: an annual challenge.
PMID- 29950433
TI - Spinal cord atrophy rates: Ready for prime time in multiple sclerosis clinical
trials?
PMID- 29950435
TI - Palliative care needs are everywhere: Where do we begin?
PMID- 29950434
TI - Neuropalliative care: Priorities to move the field forward.
AB - Neuropalliative care is an emerging subspecialty in neurology and palliative
care. On April 26, 2017, we convened a Neuropalliative Care Summit with national
and international experts in the field to develop a clinical, educational, and
research agenda to move the field forward. Clinical priorities included the need
to develop and implement effective models to integrate palliative care into
neurology and to develop and implement informative quality measures to evaluate
and compare palliative approaches. Educational priorities included the need to
improve the messaging of palliative care and to create standards for palliative
care education for neurologists and neurology education for palliative
specialists. Research priorities included the need to improve the evidence base
across the entire research spectrum from early-stage interventional research to
implementation science. Highest priority areas include focusing on outcomes
important to patients and families, developing serious conversation triggers, and
developing novel approaches to patient and family engagement, including
improvements to decision quality. As we continue to make remarkable advances in
the prevention, diagnosis, and treatment of neurologic illness, neurologists will
face an increasing need to guide and support patients and families through
complex choices involving immense uncertainty and intensely important outcomes of
mind and body. This article outlines opportunities to improve the quality of care
for all patients with neurologic illness and their families through a broad range
of clinical, educational, and investigative efforts that include complex symptom
management, communication skills, and models of care.
PMID- 29950437
TI - Spinal cord volume loss: A marker of disease progression in multiple sclerosis.
AB - OBJECTIVE: Cross-sectional studies have shown that spinal cord volume (SCV) loss
is related to disease severity in multiple sclerosis (MS). However, long-term
data are lacking. Our aim was to evaluate SCV loss as a biomarker of disease
progression in comparison to other MRI measurements in a large cohort of patients
with relapse-onset MS with 6-year follow-up. METHODS: The upper cervical SCV, the
total brain volume, and the brain T2 lesion volume were measured annually in 231
patients with MS (180 relapsing-remitting [RRMS] and 51 secondary progressive
[SPMS]) over 6 years on 3-dimensional, T1-weighted, magnetization-prepared rapid
acquisition gradient echo images. Expanded Disability Status Scale (EDSS) score
and relapses were recorded at every follow-up. RESULTS: Patients with SPMS had
lower baseline SCV (p < 0.01) but no accelerated SCV loss compared to those with
RRMS. Clinical relapses were found to predict SCV loss over time (p < 0.05) in
RRMS. Furthermore, SCV loss, but not total brain volume and T2 lesion volume, was
a strong predictor of EDSS score worsening over time (p < 0.05). The mean annual
rate of SCV loss was the strongest MRI predictor for the mean annual EDSS score
change of both RRMS and SPMS separately, while correlating stronger in SPMS.
Every 1% increase of the annual SCV loss rate was associated with an extra 28%
risk increase of disease progression in the following year in both groups.
CONCLUSION: SCV loss over time relates to the number of clinical relapses in
RRMS, but overall does not differ between RRMS and SPMS. SCV proved to be a
strong predictor of physical disability and disease progression, indicating that
SCV may be a suitable marker for monitoring disease activity and severity.
PMID- 29950436
TI - Independent home use of a brain-computer interface by people with amyotrophic
lateral sclerosis.
AB - OBJECTIVE: To assess the reliability and usefulness of an EEG-based brain
computer interface (BCI) for patients with advanced amyotrophic lateral sclerosis
(ALS) who used it independently at home for up to 18 months. METHODS: Of 42
patients consented, 39 (93%) met the study criteria, and 37 (88%) were assessed
for use of the Wadsworth BCI. Nine (21%) could not use the BCI. Of the other 28,
27 (men, age 28-79 years) (64%) had the BCI placed in their homes, and they and
their caregivers were trained to use it. Use data were collected by Internet.
Periodic visits evaluated BCI benefit and burden and quality of life. RESULTS:
Over subsequent months, 12 (29% of the original 42) left the study because of
death or rapid disease progression and 6 (14%) left because of decreased
interest. Fourteen (33%) completed training and used the BCI independently,
mainly for communication. Technical problems were rare. Patient and caregiver
ratings indicated that BCI benefit exceeded burden. Quality of life remained
stable. Of those not lost to the disease, half completed the study; all but 1
patient kept the BCI for further use. CONCLUSION: The Wadsworth BCI home system
can function reliably and usefully when operated by patients in their homes. BCIs
that support communication are at present most suitable for people who are
severely disabled but are otherwise in stable health. Improvements in BCI
convenience and performance, including some now underway, should increase the
number of people who find them useful and the extent to which they are used.
PMID- 29950438
TI - A useful communication in brain-computer interfaces.
PMID- 29950439
TI - Female sex hormones in men with migraine.
AB - OBJECTIVE: To assess the role of estradiol and testosterone in men with migraine.
METHODS: We measured 17beta-estradiol (E2) and calculated free testosterone (Tf)
in serum of 17 medication-free men with migraine and 22 men without migraine
group-matched for age and body mass index (BMI), targeted at 20 to 28 kg/m2.
Blood was sampled on a single, for migraineurs interictal, day at 9 am, 12 pm, 3
pm, and 6 pm. Migraineurs were subsequently measured 3 to 4 times daily until an
attack occurred. Clinical androgen deficiency was assessed with the Androgen
Deficiency of Ageing Men questionnaire and the Aging Males' Symptoms (AMS) scale.
We analyzed interictal data (mean +/- standard error) with repeated-measures
analysis of covariance and longitudinal data by generalized estimated equations
models. RESULTS: Compared to controls, men with migraine had a lower interictal
Tf/E2 ratio (3.9 +/- 0.4 vs 5.0 +/- 0.3, p = 0.03) due to higher E2 (96.8 +/- 6.1
vs 69.1 +/- 5.6 pmol/L, p = 0.001) and similar Tf (357.5 +/- 21.4 vs 332.6 +/-
18.7 pmol/L, p = 0.35) levels. Preictal Tf levels were increased in men with
migraine reporting premonitory symptoms (p = 0.03). Men with migraine more
frequently reported symptoms of androgen deficiency (11 of 18 [61.1%] vs 6 of 22
[27.3%], p = 0.031), which were also more frequently severe (p = 0.006); their
age- and BMI-adjusted AMS scores were higher (27.0 +/- 1.2 vs 21.0 +/- 1.0, p =
0.002). CONCLUSIONS: In this study, nonobese men with migraine exhibited
increased levels of the sex hormone estradiol and showed clinical evidence of
relative androgen deficiency. The role of estradiol in modulating migraine
susceptibility and activity in men deserves further investigations.
PMID- 29950440
TI - A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy
with rigid spine.
AB - OBJECTIVE: To describe a large series of BIN1 patients, in which a novel founder
mutation in the Roma population of southern Spain has been identified. METHODS:
Patients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers
for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations.
Clinical, histologic, radiologic, and genetic features were analyzed. RESULTS:
Eighteen patients from 13 families carried the p.Arg234Cys variant; 16 of them
were homozygous for it and 2 had compound heterozygous p.Arg234Cys/p.Arg145Cys
mutations. Both BIN1 variants have only been identified in Roma, causing 100% of
CNM in this ethnic group in our cohort. The haplotype analysis confirmed all
families are related. In addition to clinical features typical of CNM, such as
proximal limb weakness and ophthalmoplegia, most patients in our cohort presented
with prominent axial weakness, often associated with rigid spine. Severe fat
replacement of paravertebral muscles was demonstrated by muscle imaging. This
phenotype seems to be specific to the p.Arg234Cys mutation, not reported in other
BIN1 mutations. Extreme clinical variability was observed in the 2 compound
heterozygous patients for the p.Arg234Cys/p.Arg145Cys mutations, from a
congenital onset with catastrophic outcome to a late-onset disease. Screening of
European Roma controls (n = 758) for the p.Arg234Cys variant identified a carrier
frequency of 3.5% among the Spanish Roma. CONCLUSION: We have identified a BIN1
founder Roma mutation associated with a highly specific phenotype, which is, from
the present cohort, the main cause of CNM in Spain.
PMID- 29950441
TI - Doctors call for public inquiry into GMC's handling of Bawa-Garba case.
PMID- 29950442
TI - Williams review of gross negligence manslaughter in healthcare.
PMID- 29950443
TI - Integrated pathogen load and dual transcriptome analysis of systemic host
pathogen interactions in severe malaria.
AB - The pathogenesis of infectious diseases depends on the interaction of host and
pathogen. In Plasmodium falciparum malaria, host and parasite processes can be
assessed by dual RNA sequencing of blood from infected patients. We performed
dual transcriptome analyses on samples from 46 malaria-infected Gambian children
to reveal mechanisms driving the systemic pathophysiology of severe malaria.
Integrating these transcriptomic data with estimates of parasite load and
detailed clinical information allowed consideration of potentially confounding
effects due to differing leukocyte proportions in blood, parasite developmental
stage, and whole-body pathogen load. We report hundreds of human and parasite
genes differentially expressed between severe and uncomplicated malaria, with
distinct profiles associated with coma, hyperlactatemia, and thrombocytopenia.
High expression of neutrophil granule-related genes was consistently associated
with all severe malaria phenotypes. We observed severity-associated variation in
the expression of parasite genes, which determine cytoadhesion to vascular
endothelium, rigidity of infected erythrocytes, and parasite growth rate. Up to
99% of human differential gene expression in severe malaria was driven by
differences in parasite load, whereas parasite gene expression showed little
association with parasite load. Coexpression analyses revealed interactions
between human and P. falciparum, with prominent co-regulation of translation
genes in severe malaria between host and parasite. Multivariate analyses
suggested that increased expression of granulopoiesis and interferon-gamma
related genes, together with inadequate suppression of type 1 interferon
signaling, best explained severity of infection. These findings provide a
framework for understanding the contributions of host and parasite to the
pathogenesis of severe malaria and identifying new treatments.
PMID- 29950444
TI - Opiates increase the number of hypocretin-producing cells in human and mouse
brain and reverse cataplexy in a mouse model of narcolepsy.
AB - The changes in brain function that perpetuate opiate addiction are unclear. In
our studies of human narcolepsy, a disease caused by loss of
immunohistochemically detected hypocretin (orexin) neurons, we encountered a
control brain (from an apparently neurologically normal individual) with 50% more
hypocretin neurons than other control human brains that we had studied. We
discovered that this individual was a heroin addict. Studying five postmortem
brains from heroin addicts, we report that the brain tissue had, on average, 54%
more immunohistochemically detected neurons producing hypocretin than did control
brains from neurologically normal subjects. Similar increases in hypocretin
producing cells could be induced in wild-type mice by long-term (but not short
term) administration of morphine. The increased number of detected hypocretin
neurons was not due to neurogenesis and outlasted morphine administration by
several weeks. The number of neurons containing melanin-concentrating hormone,
which are in the same hypothalamic region as hypocretin-producing cells, did not
change in response to morphine administration. Morphine administration restored
the population of detected hypocretin cells to normal numbers in transgenic mice
in which these neurons had been partially depleted. Morphine administration also
decreased cataplexy in mice made narcoleptic by the depletion of hypocretin
neurons. These findings suggest that opiate agonists may have a role in the
treatment of narcolepsy, a disorder caused by hypocretin neuron loss, and that
increased numbers of hypocretin-producing cells may play a role in maintaining
opiate addiction.
PMID- 29950445
TI - Targeting the XPO1-dependent nuclear export of E2F7 reverses anthracycline
resistance in head and neck squamous cell carcinomas.
AB - Patient mortality rates have remained stubbornly high (40%) for the past 35 years
in head and neck squamous cell carcinoma (HNSCC) due to inherent or acquired drug
resistance. Thus, a critical issue in advanced SCC is to identify and target the
mechanisms that contribute to therapy resistance. We report that the
transcriptional inhibitor, E2F7, is mislocalized to the cytoplasm in >80% of
human HNSCCs, whereas the transcriptional activator, E2F1, retains localization
to the nucleus in SCC. This results in an imbalance in the control of E2F
dependent targets such as SPHK1, which is derepressed and drives resistance to
anthracyclines in HNSCC. Specifically, we show that (i) E2F7 is subject to
exportin 1 (XPO1)-dependent nuclear export, (ii) E2F7 is selectively mislocalized
in most of SCC and multiple other tumor types, (iii) mislocalization of E2F7 in
HNSCC causes derepression of Sphk1 and drives anthracycline resistance, and (iv)
anthracycline resistance can be reversed with a clinically available inhibitor of
XPO1, selinexor, in xenotransplant models of HNSCC. Thus, we have identified a
strategy to repurpose anthracyclines for use in SCC. More generally, we provide a
strategy to restore the balance of E2F1 (activator) and E2F7 (inhibitor) activity
in cancer.
PMID- 29950446
TI - Preclinical assessment of antiviral combination therapy in a genetically
humanized mouse model for hepatitis delta virus infection.
AB - Chronic delta hepatitis, caused by hepatitis delta virus (HDV), is the most
severe form of viral hepatitis, affecting at least 20 million hepatitis B virus
(HBV)-infected patients worldwide. HDV/HBV co- or superinfections are major
drivers for hepatocarcinogenesis. Antiviral treatments exist only for HBV and can
only suppress but not cure infection. Development of more effective therapies has
been impeded by the scarcity of suitable small-animal models. We created a
transgenic (tg) mouse model for HDV expressing the functional receptor for HBV
and HDV, the human sodium taurocholate cotransporting peptide NTCP. Both HBV and
HDV entered hepatocytes in these mice in a glycoprotein-dependent manner, but one
or more postentry blocks prevented HBV replication. In contrast, HDV persistently
infected hNTCP tg mice coexpressing the HBV envelope, consistent with HDV
dependency on the HBV surface antigen (HBsAg) for packaging and spread. In
immunocompromised mice lacking functional B, T, and natural killer cells, viremia
lasted at least 80 days but resolved within 14 days in immunocompetent animals,
demonstrating that lymphocytes are critical for controlling HDV infection.
Although acute HDV infection did not cause overt liver damage in this model, cell
intrinsic and cellular innate immune responses were induced. We further
demonstrated that single and dual treatment with myrcludex B and lonafarnib
efficiently suppressed viremia but failed to cure HDV infection at the doses
tested. This small-animal model with inheritable susceptibility to HDV opens
opportunities for studying viral pathogenesis and immune responses and for
testing novel HDV therapeutics.
PMID- 29950447
TI - Embryonic growth rate affects telomere attrition: an experiment in a wild bird.
AB - High growth rate is associated with a short lifespan, but the physiological basis
for this trade-off is not well known. Telomere length predicts individual
lifespan and in this study we investigated whether embryonic growth rate,
manipulated using incubation temperature, affects erythrocyte telomere length in
a wild bird species, the common tern (Sterna hirundo). A 1 degrees C lower
incubation temperature decreased growth rate by 5%, without affecting size at
hatching. The slower growth was associated with an average telomere length that
was 147 base pairs longer at hatching. If carried through to adulthood, this
effect would correspond with an approximately 3 year longer lifespan. Our results
thus suggest that an effect of growth rate on lifespan may be mediated by
telomere dynamics or a physiological process reflected by telomere length.
PMID- 29950448
TI - Avian thermoregulation in the heat: is evaporative cooling more economical in
nocturnal birds?
AB - Evaporative cooling is a prerequisite for avian occupancy of hot, arid
environments, and is the only avenue of heat dissipation when air temperatures
(Ta) exceed body temperature (Tb). Whereas diurnal birds can potentially
rehydrate throughout the day, nocturnal species typically forgo drinking between
sunrise and sunset. We hypothesized that nocturnal birds have evolved reduced
rates of evaporative water loss (EWL) and more economical evaporative cooling
mechanisms compared with diurnal species, permitting nocturnal species to
tolerate extended periods of intense heat without becoming lethally dehydrated.
We used phylogenetically informed regressions to compare EWL and evaporative
cooling efficiency [ratio of evaporative heat loss (EHL) and metabolic heat
production (MHP); EHL/MHP] among nocturnal and diurnal birds at high Ta We
analyzed variation in three response variables: (1) slope of EWL at Ta between 40
and 46 degrees C, (2) EWL at Ta=46 degrees C and (3) EHL/MHP at Ta=46 degrees C.
Nocturnality emerged as a weak, negative predictor, with nocturnal species having
slightly shallower slopes and reduced EWL compared with diurnal species of
similar mass. In contrast, nocturnal activity was positively correlated with
EHL/MHP, indicating a greater capacity for evaporative cooling in nocturnal
birds. However, our analysis also revealed conspicuous differences among
nocturnal taxa. Caprimulgids and Australian owlet-nightjars had shallower slopes
and reduced EWL compared with similarly sized diurnal species, whereas owls had
EWL rates comparable to those of diurnal species. Consequently, our results did
not unequivocally demonstrate more economical cooling among nocturnal birds. Owls
predominately select refugia with cooler microclimates, but the more frequent and
intense heat waves forecast for the 21st century may increase microclimate
temperatures and the necessity for active heat dissipation, potentially
increasing owls' vulnerability to dehydration and hyperthermia.
PMID- 29950449
TI - Fluid shift versus body size: changes of hematological parameters and body fluid
volume in hindlimb-unloaded mice, rats and rabbits.
AB - The cardiovascular system is adapted to gravity, and reactions to the loss of
gravity in space are presumably dependent on body size. The dependence of
hematological parameters and body fluid volume on simulated microgravity have
never been studied as an allometric function before. Thus, we estimated red blood
cell (RBC), blood and extracellular fluid volume in hindlimb-unloaded (HLU) or
control (attached) mice, rats and rabbits. RBC decrease was found to be size
independent, and the allometric dependency for RBC loss in HLU and control
animals shared a common power (-0.054+/-0.008) but a different Y0 coefficient
(8.66+/-0.40 and 10.73+/-0.49, respectively, P<0.05). Blood volume in HLU animals
was unchanged compared with that of controls, disregarding body size. The
allometric dependency of interstitial fluid volume in HLU and control mice shared
Y0 (1.02+/-0.09) but had different powers N (0.708+/-0.017 and 0.648+/-0.016,
respectively, P<0.05), indicating that the interstitial fluid volume increase
during hindlimb unloading is more pronounced in larger animals. Our data
underscore the importance of size-independent mechanisms of cardiovascular
adaptation to weightlessness. Despite the fact that the use of mice hampers
application of a straightforward translational approach, this species is useful
for gravitational biology as a tool to investigate size-independent mechanisms of
mammalian adaptation to microgravity.
PMID- 29950450
TI - Changes in hemolymph total CO2 content during the water-to-air respiratory
transition of amphibiotic dragonflies.
AB - Dragonflies (Odonata, Anisoptera) are amphibiotic; the nymph is aquatic and
breathes water using a rectal gill before metamorphosing into the winged adult,
which breathes air through spiracles. While the evolutionary and developmental
transition from water breathing to air breathing is known to be associated with a
dramatic rise in internal CO2 levels, the changes in blood-gas composition
experienced by amphibiotic insects, which represent an ancestral air-to-water
transition, are unknown. This study measured total CO2 (TCO2) in hemolymph
collected from aquatic nymphs and air-breathing adults of Anax junius, Aeshna
multicolor (Aeshnidae), Libellula quadrimaculata and Libellulaforensis
(Libellulidae). Hemolymph PCO2 was also measured in vivo in both aeshnid nymphs
and marbled crayfish (Procambarus fallax. f. virginalis) using a novel fiber
optic CO2 sensor. The hemolymph TCO2 of the pre- and early-final instar nymphs
was found to be significantly lower than that of the air-breathing adults.
However, the TCO2 of the late-final instar aeshnid nymphs was not significantly
different from that of the air-breathing adults, despite the late-final nymphs
still breathing water. TCO2 and PCO2 were also significantly higher in the
hemolymph of early-final aeshnid nymphs compared with values for the water
breathing crayfish. Thus, while dragonfly nymphs show an increase in internal CO2
as they transition from water to air, from an evolutionary standpoint, the
nymph's ability to breathe water is associated with a comparatively minor
decrease in hemolymph TCO2 relative to that of the air-breathing adult.
PMID- 29950451
TI - Active acoustic interference elicits echolocation changes in heterospecific bats.
AB - Echolocating bats often forage in the presence of both conspecific and
heterospecific individuals, which have the potential to produce acoustic
interference. Recent studies have shown that at least one bat species, the
Brazilian free-tailed bat (Tadarida brasiliensis), produces specialized social
signals that disrupt the sonar of conspecific competitors. We herein discuss the
differences between passive and active jamming signals and test whether
heterospecific jamming occurs in species overlapping spatiotemporally, as well as
whether such interference elicits a jamming avoidance response. We compare the
capture rates of tethered moths and the echolocation parameters of big brown bats
(Eptesicus fuscus) challenged with the playback of the jamming signal normally
produced by Brazilian free-tailed bats and playback of deconstructed versions of
this signal. There were no differences in the capture rates of targets with and
without the jamming signal, although significant changes in both spectral and
temporal features of the bats' echolocation were observed. These changes are
consistent with improvements of the signal-to-noise ratio in the presence of
acoustic interference. Accordingly, we propose to expand the traditional
definition of the jamming avoidance response, stating that echolocation changes
in response to interference should decrease similarity between the two signals,
to include any change that increases the ability to separate returning echoes
from active jamming stimuli originating from conspecific and heterospecific
organisms. Flexibility in echolocation is an important characteristic for
overcoming various forms of acoustic interference and may serve a purpose in
interspecific interactions as well as intraspecific ones.
PMID- 29950453
TI - Recommendations for the Design and Analysis of In Vivo Electrophysiology Studies.
PMID- 29950454
TI - Abeta-Mediated Dysregulation of F-Actin Nanoarchitecture Leads to Loss of
Dendritic Spines and Alzheimer's Disease-Related Cognitive Impairments.
PMID- 29950452
TI - Exploring the links between cancer and placenta development.
AB - The development of metastatic cancer is a multistage process, which often
requires decades to complete. Impairments in DNA damage control and DNA repair in
cancer cell precursors generate genetically heterogeneous cell populations.
However, despite heterogeneity most solid cancers have stereotypical behaviours,
including invasiveness and suppression of immune responses that can be unleashed
with immunotherapy targeting lymphocyte checkpoints. The mechanisms leading to
the acquisition of stereotypical properties remain poorly understood.
Reactivation of embryonic development processes in cells with unstable genomes
might contribute to tumour expansion and metastasis formation. However, it is
unclear whether these events are linked to immune response modulation. Tumours
and embryos have non-self-components and need to avoid immune responses in their
microenvironment. In mammalian embryos, neo-antigens are of paternal origin,
while in tumour cells DNA mismatch repair and replication defects generate them.
Inactivation of the maternal immune response towards the embryo, which occurs at
the placental-maternal interface, is key to ensuring embryonic development. This
regulation is accomplished by the trophoblast, which mimics several malignant
cell features, including the ability to invade normal tissues and to avoid host
immune responses, often adopting the same cancer immunoediting strategies. A
better understanding as to whether and how genotoxic stress promotes cancer
development through reactivation of programmes occurring during early stages of
mammalian placentation could help to clarify resistance to drugs targeting immune
checkpoint and DNA damage responses and to develop new therapeutic strategies to
eradicate cancer.
PMID- 29950455
TI - Effectiveness of targeting the health promotion settings for non-communicable
disease control in low/middle-income countries: systematic review protocol.
AB - INTRODUCTION: Settings-based approaches to health promotion, involving holistic
and multidisciplinary methods, which integrate action across risk factors are
important. Major advantage of focusing on these settings is the continuous and
intensive contact with the participant. Despite the apparent advantages of
addressing non-communicable diseases (NCDs) using targeted interventions for
several developed country settings, a relative lack of evidence of effectiveness
of such interventions in low/middle-income countries has led to poor allocation
of resources towards these interventions. The focus is therefore on the settings
rather than any one condition, and we therefore expect the findings to generalise
to NCD prevention and control efforts. We intend to estimate the effectiveness of
targeted interventions in low/middle-income countries. METHODS AND ANALYSIS: We
will search PubMed, Excerpta Medica Database, OVID, WHO Library and The Cochrane
Library from the year 2000 to March 2018 without language restrictions. Study
designs to be included will be randomised controlled trials. The primary outcome
of effectiveness will be the percentage change in population having different
behavioural risk factors. Subgroup analyses will be performed, and sensitivity
analyses will be conducted to assess the robustness of the findings. ETHICS AND
DISSEMINATION: No ethical issues are foreseen. The Institute Ethics Committee of
the Post Graduate Institute of Medical Education and Research approved the
doctoral research protocol under which this review is being done. Dissemination
will be done by submitting scientific articles to academic peer-reviewed
journals. We will present the results at relevant conferences and meetings. STUDY
DESIGN: Systematic review. PROSPERO REGISTRATION NUMBER: CRD42016042647; Pre
results.
PMID- 29950456
TI - Impact of a modified version of baby-led weaning on iron intake and status: a
randomised controlled trial.
AB - OBJECTIVE: To determine the iron intake and status of infants following a version
of baby-led weaning (BLW) modified to prevent iron deficiency (Baby-Led
Introduction to SolidS; BLISS) compared with those of infants following
traditional spoon-feeding. DESIGN, PARTICIPANTS AND INTERVENTION: This randomised
controlled trial included 206 participants assigned to control (n=101) or BLISS
(n=105) groups. Both groups received standard midwifery and 'Well Child' care.
BLISS participants received eight additional visits (from before birth to 9
months) providing education and support on the BLISS approach to complementary
feeding (ie, BLW modified to increase iron intake). The primary outcome of the
BLISS study (growth) has been previously reported. This paper reports the key
prespecified secondary outcomes, iron intake and iron status. OUTCOME MEASURES:
Intake of iron and key absorption modifiers were assessed using weighed 3-day
diet records at 7 and 12 months. A venipuncture blood sample was collected at 12
months to determine plasma ferritin, haemoglobin, soluble transferrin receptor, C
reactive protein and alpha1-acid glycoprotein concentrations; and body iron was
calculated. RESULTS: Differences in median dietary iron intakes between the
control and BLISS groups were not significant at 7 (difference 0.6 mg/day; 95% CI
-1.0 to 2.3) or 12 (-0.1 mg/day; -1.6 to 1.4) months of age. Similarly, there
were no significant differences in plasma ferritin concentration (difference -2.6
ug/L; 95% CI -10.9 to 5.8), body iron (0.04 mg/kg; -1.1 to 1.2) or the prevalence
of depleted iron stores, early functional iron deficiency or iron deficiency
anaemia (all p>=0.65) at 12 months of age. CONCLUSIONS: A baby-led approach to
complementary feeding does not appear to increase the risk of iron deficiency in
infants when their parents are given advice to offer 'high-iron' foods with each
meal. TRIAL REGISTRATION NUMBER: ACTRN12612001133820; Pre-results.
PMID- 29950457
TI - Policies supporting informal caregivers across Canada: a scoping review protocol.
AB - INTRODUCTION: As the population ages, governments worldwide have begun seeking
ways to support informal caregiving. In this light, Canada is no exception, but
despite the centrality of the informal care strategy in elder care, we know
little about the intertwining and overlapping policies that have been implemented
to support informal caregivers providing assistance to the elderly, and to fellow
citizens with disabilities. This review aims to identify the diversity of
Canadian national, provincial and territorial policies supporting informal
caregivers. It seeks, from its generalist focus on all informal care, to draw out
specific observations and lessons for the elder care policy environment. METHODS
AND ANALYSIS: Given the vast and multidisciplinary nature of the literature on
informal care policy, as well as the paucity of existing knowledge syntheses, we
will adopt a scoping review methodology. We will follow the framework developed
by Arksey and O'Malley that entails six stages, including: (1) identifying the
research question(s); (2) searching for relevant studies; (3) selecting studies;
(4) charting the data; (5) collating, summarising and reporting the results; (6)
and conducting consultation exercises. We will conduct these stages iteratively
and reflexively, making adjustments and repetitions when appropriate to ensure we
have covered the literature as comprehensively as possible. We will pursue an
iterative integrated knowledge translation (iKT) strategy engaging our knowledge
users through all stages of the review. ETHICS AND DISSEMINATION: By adopting an
iKT strategy we will ensure our knowledge users directly contribute to the
project's policy relevant publications. Upon completion of the review, we will
present the findings at academic conferences, publishing a research report, along
with an academic peer-reviewed article. Our intent is to develop an online, free
access evidence repository that catalogues the full range of Canada's English
language informal care support policies. Finally, the completed review will allow
us to publish a series of policy briefs in collaboration with knowledge users
illustrating how to promote and better implement informal care support policies.
Our study has received ethics approval from the University of Calgary Conjoint
Ethics Board.
PMID- 29950458
TI - Development of an interprofessional collaboration competency scale for children
with medical complexity.
AB - OBJECTIVE: To develop and validate an interprofessional collaboration competency
scale for children with medical complexity (ICC-CMC). These children have the
most complex healthcare needs, complicated chronic conditions, severe functional
limitations and often need a considerable amount of healthcare resources. DESIGN:
Cross-sectional study. SETTING: The self-administered ICC-CMC questionnaire was
developed based on a literature review and 12 expert interviews. PARTICIPANTS:
Participants were 2347 interprofessionals from the health, medical, welfare and
education fields in seven prefectures in Japan. MAIN OUTCOME MEASURES: We used
Cronbach's alpha values to assess the internal consistency of the scale.
Construct validity was confirmed with confirmatory factor analysis, and an
existing scale was administered to assess criterion-related validity. RESULTS: In
total, 378 professionals provided valid responses. Exploratory and confirmatory
factor analyses identified 12 items on three factors: 'sharing needs assessment
skills', 'resource development skills' and 'creative networking skills'. The
final model showed good fit on four indices (eg, goodness of fit index: 0.925).
The Cronbach's alpha for the entire scale was 0.93 and was above 0.80 for each
factor. The correlation coefficient between the existing scale and the ICC-CMC
was 0.72 (p<0.001). CONCLUSIONS: The ICC-CMC demonstrated acceptable internal
consistency and validity. The scale has potential use in advancing professionals'
individual practice and team performance in interprofessional collaboration. In
addition, the ICC-CMC has the potential of improving satisfaction and outcomes
for children with medical complexity and their families.
PMID- 29950460
TI - Effectiveness of policy and risk targeting for opioid-related risk mitigation: a
randomised programme evaluation with stepped-wedge design.
AB - INTRODUCTION: There is an epidemic of opioid use related to adverse events and
deaths in the USA. The rates of chronic pain, mental illness and substance use
disorder are higher at the Veterans Health Administration (VHA) compared with the
general US population. The 2016 Comprehensive Addiction and Recovery Act requires
the VHA to improve opioid therapy strategies in treating patients and to ensure
responsible prescribing practices. The Stratification Tool for Opioid Risk
Mitigation (STORM) is a web-based dashboard that prioritises review of VHA
patients receiving opioids based on their risk. The VHA Partnered Evidence-based
Policy Resource Center is coordinating a multiyear evaluation of STORM and
aspects of the VHA policy that mandate case review of patients identified by
STORM as very high risk. METHODS AND ANALYSIS: This stepped-wedge cluster
randomised controlled trial will test two hypotheses: (1) VHA medical centres
randomised to facilitation for not meeting the targeted case review rate will
achieve lower opioid-related serious adverse events (SAEs), relative to
facilities not randomised to facilitation and (2) Patients whose cases are
required to be reviewed will have a lower rate of opioid-related SAEs compared
with comparable risk patients whose cases are not required to be reviewed.
Patients who receive an opioid prescription at VHA medical centres will be
followed for a minimum of 3 months after their first opioid prescription. Follow
up will continue until the last day of the project or death. The data will be
analysed using an intention-to-treat approach with patient-month-level Cox
proportional hazards models for both interventions. ETHICS AND DISSEMINATION:
Evaluation of the randomised roll-out was approved by the VA Boston Healthcare
System Institutional Review Board (IRB) and Research & Development Committees
(Protocol # 3069). Findings will be published in peer-reviewed journals and
presentations at national conference meetings. TRIAL REGISTRATION NUMBER:
ISRCTN16012111.
PMID- 29950459
TI - Exogenous sex steroid hormones and asthma in females: protocol for a population
based retrospective cohort study using a UK primary care database.
AB - INTRODUCTION: Female sex steroid hormones have been implicated in sex-related
differences in the development and clinical outcomes of asthma. The role of
exogenous sex steroids, however, remains unclear. Our recent systematic review
highlighted the lack of high-quality population-based studies investigating this
subject. We aim to investigate whether the use of hormonal contraception and
hormone replacement therapy (HRT), subtypes and route of administration are
associated with asthma onset and clinical outcomes in reproductive age and
perimenopausal/postmenopausal females. METHODS AND ANALYSIS: Using the Optimum
Patient Care Research Database (OPCRD), a national primary care database in the
UK, we will construct a retrospective longitudinal cohort of reproductive age (16
45 years) and perimenopausal/postmenopausal (46-70 years) females. We will
estimate the risk of new-onset asthma using Cox regression and multilevel
modelling for repeated asthma outcomes, such as asthma attacks. We will adjust
for confounding factors in all analyses. We will evaluate interactions between
the use of exogenous sex hormones and body mass index and smoking by calculating
the relative excess risk due to interaction and the attributable proportion due
to interaction. With 90% power, we need 23 700 reproductive age females to detect
a 20% reduction (risk ratio 0.8) in asthma attacks for use of any hormonal
contraception and 6000 perimenopausal/postmenopausal females to detect a 40%
(risk ratio 1.40) increased risk of asthma attacks for use of any HRT. ETHICS AND
DISSEMINATION: We have obtained approval (ADEPT1317) from the Anonymised Data
Ethics and Protocol Transparency Committee which grants project-specific ethics
approvals for the use of OPCRD data. Optimum Patient Care has an existing NHS
Health Research Authority ethics approval for the use of OPCRD data for research
(15/EM/150). We will present our findings at national and international
scientific meetings and publish the results in international peer-reviewed
journals. TRIAL REGISTRATION NUMBER: EUPAS22967.
PMID- 29950461
TI - Derivation and validation of a chief complaint shortlist for unscheduled acute
and emergency care in Uganda.
AB - OBJECTIVES: Derive and validate a shortlist of chief complaints to describe
unscheduled acute and emergency care in Uganda. SETTING: A single, private, not
for profit hospital in rural, southwestern Uganda. PARTICIPANTS: From 2009 to
2015, 26 996 patient visits produced 42 566 total chief complaints for the
derivation dataset, and from 2015 to 2017, 10 068 visits produced 20 165 total
chief complaints for the validation dataset. METHODS: A retrospective review of
an emergency centre quality assurance database was performed. Data were
abstracted, cleaned and refined using language processing in Stata to produce a
longlist of chief complaints, which was collapsed via a consensus process to
produce a shortlist and turned into a web-based tool. This tool was used by two
local Ugandan emergency care practitioners to categorise complaints from a second
longlist produced from a separate validation dataset from the same study site.
Their agreement on grouping was analysed using Cohen's kappa to determine inter
rater reliability. The chief complaints describing 80% of patient visits from
automated and consensus shortlists were combined to form a candidate chief
complaint shortlist. RESULTS: Automated data cleaning and refining recognised
95.8% of all complaints and produced a longlist of 555 chief complaints. The
consensus process yielded a shortlist of 83 grouped chief complaints. The second
validation dataset was reduced in Stata to a longlist of 451 complaints. Using
the shortlist tool to categorise complaints produced 71.5% agreement, yielding a
kappa of 0.70 showing substantial inter-rater reliability. Only one complaint did
not fit into the shortlist and required a free-text amendment. The two shortlists
were identical for the most common 14 complaints and combined to form a candidate
list of 24 complaints that could characterise over 80% of all emergency centre
chief complaints. CONCLUSIONS: Shortlists of chief complaints can be generated to
improve standardisation of data entry, facilitate research efforts and be
employed for paper chart usage.
PMID- 29950462
TI - We12BFit!-Improving lifestyle physical activity in children aged 7-12 years with
developmental coordination disorder: protocol of a multicentre single-arm mixed
method study.
AB - INTRODUCTION: Children with developmental coordination disorder (DCD) are less
physically active than their typically developing peers. No substantiated
interventions are available to address this issue. Therefore, this study aims to
describe the design and rationale of (1) a family-focused intervention to
increase motivation for physical activity (PA) and, indirectly, lifestyle PA in
children aged 7-12 years with DCD and (2) the methods to examine its preliminary
effectiveness and feasibility. METHODS AND ANALYSIS: This intervention is the
second part of a more comprehensive, multidisciplinary treatment called We12BFit!
The intervention was developed using the steps of treatment theory which includes
the concept of targets, mechanism of action and essential ingredients. The
content of the intervention is based on the transtheoretical model of change
(TTM). In the intervention, the motivation for PA will be targeted through
application of behaviour change strategies that fit the stages of the TTM. The
modes of delivery include: pedometer, poster, parent meeting, booklet and
coaching. At least 19 children with DCD, aged 7-12 years, will be included from
two schools for special education and two rehabilitation centres. The
intervention will be evaluated using a single-arm mixed-method design.
Effectiveness will be assessed at three instances by using ActiGraph
accelerometers accompanied by an activity log. Feasibility will be assessed using
interviews with the participants and coaches. This evaluation may add to our
understanding of motivation for PA in children with DCD and may eventually
improve the rehabilitation programme of children with DCD. ETHICS AND
DISSEMINATION: The study has been approved by the Medical Ethics Committee of the
University Medical Center of Groningen (METc 2015.216). We will disseminate the
final results to the public through journal publications and presentations for
practice providers and scientists. A final study report will also be provided to
funding organisations. PROTOCOL VERSION: 4, 12 April 2018. TRIAL REGISTRATION
NUMBER: NTR6334; Pre-results.
PMID- 29950463
TI - Natural corollaries and recovery after acute ACL injury: the NACOX cohort study
protocol.
AB - INTRODUCTION: Anterior cruciate ligament (ACL) injury can result in joint
instability, decreased functional performance, reduced physical activity and
quality of life and an increased risk for post-traumatic osteoarthritis. Despite
the development of new treatment techniques and extensive research, the complex
and multifaceted nature of ACL injury and its consequences are yet to be fully
understood. The overall aim of the NACOX study is to evaluate the natural
corollaries and recovery after an ACL injury. METHODS AND ANALYSIS: The NACOX
study is a multicentre prospective prognostic cohort study of patients with acute
ACL injury. At seven sites in Sweden, we will include patients aged 15-40 years,
within 6 weeks after primary ACL injury. Patients will complete questionnaires at
multiple occasions over the 3 years following injury or the 3 years following ACL
reconstruction (for participants who have surgical treatment). In addition, a
subgroup of 130 patients will be followed with clinical examinations, several
imaging modalities and biological samples. Data analyses will be specific to each
aim. ETHICS AND DISSEMINATION: This study has been approved by the regional
Ethical committee in Linkoping, Sweden (Dnr 2016/44-31 and 2017/221-32). We plan
to present the results at national and international conferences and in peer
reviewed scientific journals. Participants will receive a short summary of the
results following completion of the study. TRIAL REGISTRATION NUMBER:
NCT02931084.
PMID- 29950464
TI - Cauterisation versus fibrin glue for conjunctival autografting in primary
pterygium surgery (CAGE CUP): study protocol of a randomised controlled trial.
AB - INTRODUCTION: Pterygium is a non-cancerous growth of the conjunctival tissue over
the cornea that may lead to visual impairment in advanced stages, restriction of
ocular motility, chronic inflammation and cosmetic concerns. Surgical removal is
the treatment of choice, but recurrence of pterygium is a frequent problem. It
has been previously shown that fibrin glue may result in less recurrence and may
take less time than sutures for fixing the conjunctival graft in place during
pterygium surgery. However, fibrin glue is a biological material and it carries
the risk of transmitting infectious agents from pooled and single-donor blood
donors and anaphylaxis in susceptible individuals. Cauterisation is another
surgical option, and it would be advantageous to know whether cauterisation may
be superior surgical option compared with fibrin glue. This protocol describes
the rationale and design of the randomised controlled trial (RCT) in which we
will compare cauterisation versus fibrin glue for conjunctival autografting in
primary pterygium surgery. METHODS AND ANALYSES: This will be a parallel group
RCT comparing cauterisation versus fibrin glue for conjunctival autografting in
primary pterygium surgery. Computer-generated randomisation will be used, and
allocation concealment will be conducted using sequentially numbered opaque
sealed envelopes. Surgeons will not be blinded to the procedures, but
participants, other investigators and outcome assessors will be blinded. Adult
participants with primary pterygium operated in a tertiary hospital in Split,
Croatia, will be included. Primary outcome will be recurrence of pterygium,
defined as any regrowth of tissue from the area of excision across the limbus
onto the cornea after 180 days. ETHICS AND DISSEMINATION: The trial was approved
by the ethics review board of the University Hospital Split (500-03/17-01/68).
Results will be disseminated at conferences and through peer-reviewed
publications. TRIAL REGISTRATION NUMBER: NCT03321201; Pre-results.
PMID- 29950466
TI - Cardiovascular toxicity of targeted therapies for cancer: a protocol for an
overview of systematic reviews.
AB - INTRODUCTION: The introduction of targeted therapies for cancer has contributed
to dramatic improvements in patient survival. Nevertheless, several targeted
therapies have been associated with 'off-target' adverse effects, based on
varying levels of evidence. To date, this evidence has not been systematically
synthesised. We will synthesise published systematic review evidence of
cardiovascular toxicity associated with targeted cancer therapies. METHODS AND
ANALYSIS: We will include systematic reviews of randomised controlled trials and
observational studies that report on cardiovascular outcomes for individual
agents. We will identify systematic reviews by applying predeveloped,
standardised search strategies within Embase, Medline and Cochrane Central. Two
independent reviewers will identify reviews published up to 31 December 2016
using predefined eligibility criteria. They will resolve ambiguous cases through
consensus, arbitrated by a third reviewer if required. The reviewers will extract
and report data according to methodological guidelines for overviews provided by
the Cochrane Collaboration, Joanna Briggs Institute and the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses Protocols. They will assess the
quality of included reviews by applying the Assessment of Multiple Systematic
Reviews tool. They will judge the quality of evidence in included reviews based
on their assessment of bias and incorporation into the interpretation of
findings. In synthesising the evidence, we will classify agents based on
systematic review evidence of toxicity (sufficient, probable, possible or
indeterminate) for specific cardiovascular outcomes (congestive heart failure,
myocardial infarction, ischaemic heart disease, left ventricular ejection
fraction decline, cerebrovascular disease, pulmonary embolism, thrombosis and
hypertension). This will provide clinicians and patients with an accessible
synthesis based on robust methodology. ETHICS AND DISSEMINATION: Ethics approval
is not required for overviews. We will conduct the study in collaboration with
consumer representatives. We will submit results for peer-review publication, and
disseminate them through established clinical and consumer networks. PROSPERO
REGISTRATION NUMBER: CRD42017080014.
PMID- 29950465
TI - A Reduction in Time with Electronic Monitoring In Stroke (ARTEMIS): study
protocol for a randomised multicentre trial.
AB - INTRODUCTION: Time is the most crucial factor limiting efficacy of intravenous
thrombolysis (IVT) and intra-arterial thrombectomy (IAT). The delay between
alarming the Emergency Medical Services (EMS) dispatch office and IVT/IAT
initiation, that is, the 'total system delay' (TSD), depends on logistics and
team effort. A promising method to reduce TSD is real-time audio-visual feedback
to caregivers involved. With 'A Reduction in Time with Electronic Monitoring in
Stroke' (ARTEMIS), we aim to investigate the effect of real-time audio-visual
feedback on actual TSD to IVT/IAT to caregivers. METHODS AND ANALYSIS: ARTEMIS is
a multiregional, multicentre, randomised open end-point trial including patients
>=18 years considered IVT/IAT-eligible by the EMS dispatch office or on-site EMS
personnel. Patients are electronically tracked and randomised for real-time audio
visual feedback on TSD to caregivers via premounted handhelds and tablets
throughout the TSD trajectory. Primary outcome is TSD to IVT/IAT. Secondary
outcomes comprise proportion of IVT/IAT-treated patients, symptomatic
intracerebral haemorrhage, IVT/IAT-treated stroke mimics, clinical outcome after
three months and cost-effectiveness. Separate analyses for IAT-patients with or
without prior IVT, within or out of office hours and EMS region will be
performed. With 75 IAT-patients and 225 IVT-patients in each arm, we will be able
to demonstrate a 20 min difference in TSD to IAT and a 10 min difference in TSD
to IVT (p=0.05 and power=0.8). ETHICS AND DISSEMINATION: Study findings will be
disseminated through peer-reviewed journals and (inter)national conference
presentations. TRIAL REGISTRATION NUMBER: NCT02808806; Pre-results.
PMID- 29950467
TI - Association between presenteeism and health-related quality of life among
Japanese adults with chronic lower back pain: a retrospective observational
study.
AB - OBJECTIVES: This study investigated the relationship between presenteeism and
health-related quality of life (HRQoL) among Japanese adults with chronic lower
back pain (CLBP). DESIGN: This was a retrospective, cross-sectional study.
SETTING: Data were collected via a self-administered online survey of the
Japanese adult general population. PARTICIPANTS: The present study used 2014
Japan National Health and Wellness Survey (NHWS) data (n=30 000). Specifically,
data were included from NHWS respondents who self-reported being employed in the
past week and having experienced LBP in the past month, with these symptoms
lasting for at least 3 months (n=239). 84 (35.1%) participants in this study were
female. PRIMARY AND SECONDARY OUTCOME MEASURES: Presenteeism and HRQoL were
measured using the Work Productivity and Activity Impairment Questionnaire
General Health (categorical (none: 0%, low: 10%-20%, high: >=30%) and continuous)
and Medical Outcomes Study 36-Item Short Form Health Survey, respectively.
Covariates included patient demographics, health characteristics, pain
characteristics and depression severity (Patient Health Questionnaire). RESULTS:
Presenteeism was reported by 77.4% of respondents. High (vs no) presenteeism
related to more severe pain in the prior week (4.9+/-2.2 vs 3.6+/-2.1, p=0.001)
and currently (5.1+/-2.1 vs 3.9+/-3.9, p=0.007), more pain sites (1.9+/-1.6 vs
1.1+/-1.4, p=0.004) and greater depression severity (7.5+/-6.5 vs 3.6+/-3.6,
p<0.001). Adjusting for covariates, high (vs no) presenteeism related to lower
mental and physical HRQoL. For low versus no presenteeism, significant HRQoL
differences were observed in general health (43.0, 95% CI 40.3 to 45.6 vs 46.9,
95% CI 43.9 to 49.8, p=0.015). CONCLUSIONS: Most respondents experienced
presenteeism. Those with high or low presenteeism had poorer HRQoL than
respondents with no presenteeism. Monitoring presenteeism rates may help identify
workers with an unmet need for better CLBP-related pain management.
PMID- 29950468
TI - Improving public understanding of 'overdiagnosis' in England: a population survey
assessing familiarity with possible terms for labelling the concept and
perceptions of appropriate terminology.
AB - OBJECTIVES: Communicating the concept of 'overdiagnosis' to lay individuals is
challenging, partly because the term itself is confusing. This study tested
whether alternative descriptive labels may be more appropriate. DESIGN:
Questionnaire preceded by a description of overdiagnosis. SETTING: Home-based,
computer-assisted face-to-face survey. PARTICIPANTS: 2111 adults aged 18-70 years
in England recruited using random location sampling by a survey company. Data
from 1888 participants were analysed after exclusions due to missing data.
INTERVENTIONS: Participants were given one of two pieces of text describing
overdiagnosis, allocated at random, adapted from National Health Service breast
and prostate cancer screening leaflets. PRIMARY AND SECONDARY OUTCOME MEASURES:
Main outcomes were which of several available terms (eg, 'overdetection')
participants had previously encountered and which they endorsed as applicable
labels for the concept described. Demographics and previous exposure to screening
information were also measured. Main outcomes were summarised with descriptive
statistics. Predictors of previously encountering at least one term, or endorsing
at least one as making sense, were assessed using binary logistic regression.
RESULTS: 58.0% of participants had not encountered any suggested term; 44.0% did
not endorse any as applicable labels. No term was notably familiar; the
proportion of participants who had previously encountered each term ranged from
15.9% to 28.3%. Each term was only endorsed as applicable by a minority (range:
27.6% to 40.4%). Notable predictors of familiarity included education, age and
ethnicity; participants were less likely to have encountered terms if they were
older, not white British or had less education. Findings were similar for both
pieces of information. CONCLUSIONS: Familiarity with suggested terms for
overdiagnosis and levels of endorsement were low, and no clear alternative labels
for the concept were identified, suggesting that changing terminology alone would
do little to improve understanding, particularly for some population groups.
Explicit descriptions may be more effective.
PMID- 29950469
TI - Assessing the ability of the Drug-Associated Risk Tool (DART) questionnaire to
stratify hospitalised older patients according to their risk of drug-related
problems: a cross-sectional validation study.
AB - OBJECTIVES: The Drug-Associated Risk Tool (DART) has been developed as a self
administered questionnaire for patients with the aim of stratifying patients
according to their risk of drug-related problems (DRPs). We aimed to validate the
ability of the questionnaire to distinguish between hospitalised patients showing
lower and higher numbers of DRPs. DESIGN: Cross-sectional study assessing the
questionnaire's concurrent criterion validity. SETTING: Five geriatric and the
associated physical and neurological rehabilitation wards of a Swiss regional
secondary care hospital with 617 beds. PARTICIPANTS: We recruited 110 patients
from a total of 437 admissions. Exclusion criteria were insufficient knowledge in
spoken or written German, medical conditions preventing meaningful conversations
and already receiving pharmacy services. INTERVENTIONS: Comprehensive pharmacist
led clinical medication reviews were performed, including patient interviews, to
identify potential and manifest DRPs. A cluster analysis was conducted to assess
the discriminatory potential of the DART to group patients according to number
(low and high) of identified DRPs. A subsequent discriminatory function analysis
was performed to reduce the number of items. We determined which DART items may
be used to trigger what type of medication review. RESULTS: Recruited patients
had a median age of 79 years and were prescribed a median of 11 drugs. Patients
with a median DART score of 10 and a median of 3 DRPs represented one cluster,
whereas patients with a median DART score of 15 and a median of 8 DRPs
represented another cluster. Discriminatory function analysis reduced the
questionnaire to five items with a moderate to strong correlation with the number
of DRPs per patient (Spearman's rank correlation rho=0.44). Additional items were
associated with patients benefiting from interviews. CONCLUSIONS: As a self
administered questionnaire for patients, the DART may be used to stratify
hospitalised non-acute older patients in groups of having low and high likelihood
of DRPs. The analyses showed that a short form of the DART can be used instead of
the full tool to identify older inpatients at risk for DRPs. Additional eight
items from the DART may be used to initiate additional clinical pharmacy
services. The linkage between certain DART questions and type of medication
review enables pharmacist resource allocation.
PMID- 29950470
TI - Oxidative stress and DNA damage in a long-term hexavalent chromium-exposed
population in North China: a cross-sectional study.
AB - OBJECTIVE: The International Agency for Research on Cancer classifies hexavalent
chromium (Cr(VI)) as a human carcinogen. As reported, cancer mortality was higher
in Cr(VI)-contaminated areas. Scientists have recommended studying its health
impact on people living in contaminated areas. This study aims to evaluate the
health risk for people living in Cr(VI)-contaminated areas. DESIGN: We conducted
a cross-sectional study in rural areas of north-eastern China. Malondialdehyde
(MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase
(CAT) were used as oxidative stress parameters, and 8-hydroxy-2 deoxyguanosine (8
OHdG) as a DNA damage biomarker. We collected information on demographics,
lifestyles and length of residence from all participants using a questionnaire.
Biological specimens and environmental media samples were collected on the same
day as the survey was done. We used t-test, chi2 test, Wilcoxon rank-sum test and
multivariate linear regression analysis. PARTICIPANTS: The study included 319
participants exposed to Cr(VI) and 307 unexposed participants, with 447 women and
179 men. These participants met the following criteria: (1) living in the areas
for more than 10 years; (2) age older than 18 years; and (3) without occupational
chromium exposure. RESULTS: Our study revealed that serum concentration of MDA
(p<0.001), serum activities of CAT (p<0.001) and GSH-Px (p<0.001), as well as
urine concentration of 8-OHdG (p=0.008) in the exposed group were significantly
higher than those in the unexposed group. However, serum SOD activity was
significantly lower in the exposed group, compared with that in the unexposed
group (p<0.001). Cr(VI) exposure and smoking have an interaction effect on GSH-Px
activity (p<0.05). Cr(VI) exposure and alcohol drinking also have an interaction
effect on GSH-Px activity (p<0.05). Longer residence in the exposed areas
increased the oxidative levels (p<0.05). CONCLUSIONS: The findings of this study
showed elevated oxidative stress and DNA damage in people exposed to Cr(VI).
PMID- 29950471
TI - Characteristics and treatment of African-American and European-American patients
with resistant hypertension identified using the electronic health record in an
academic health centre: a case-control study.
AB - OBJECTIVE: To identify patients with hypertension with resistant and controlled
blood pressure (BP) using electronic health records (EHRs) in order to elucidate
practices in the real-world clinical treatment of hypertension and to enable
future genetic studies. DESIGN: Using EHRs, we developed and validated algorithms
to identify patients with resistant and controlled hypertension. SETTING: An
academic medical centre in Nashville, Tennessee. POPULATION: European-American
(EA) and African-American (AA) patients with hypertension. MAIN OUTCOME MEASURES:
Demographic characteristics: race, age, gender, body mass index, outpatient BPs
and the history of diabetes mellitus, chronic kidney disease stage 3, ischaemic
heart disease, transient ischaemic attack, atrial fibrillation and sleep apnoea.
MEDICATION TREATMENT: All antihypertensive medication classes prescribed to a
patient at the time of classification and ever prescribed following
classification. RESULTS: The algorithms had performance metrics exceeding 92%.
The prevalence of resistant hypertension in the total hypertensive population was
7.3% in EA and 10.5% in AA. At diagnosis, AA were younger, heavier, more often
female and had a higher incidence of type 2 diabetes and higher BPs than EA. AA
with resistant hypertension were more likely to be treated with vasodilators,
dihydropyridine calcium channel blockers and alpha-2 agonists while EA were more
likely to be treated with angiotensin receptor blockers, renin inhibitors and
beta blockers. Mineralocorticoid receptor antagonists use was increased in
patients treated with more than four antihypertensive medications compared with
patients treated with three (12.4% vs 2.6% in EA, p<0.001; 12.3% vs 2.8% in AA,
p<0.001). The number of patients treated with a mineralocorticoid receptor
antagonist increased to 37.4% in EA and 41.2% in AA over a mean follow-up period
of 7.4 and 8.7 years, respectively. CONCLUSIONS: Clinical treatment of resistant
hypertension differs in EA and AA patients. These results demonstrate the
feasibility of identifying resistant hypertension using an EHR.
PMID- 29950472
TI - Health system costs of potentially inappropriate prescribing in Ontario, Canada:
a protocol for a population-based cohort study.
AB - INTRODUCTION: Adverse drug events (ADEs) are common in older persons and
contribute significantly to emergency department visits, hospitalisations and
mortality. ADEs are often due to potentially inappropriate prescriptions (PIP) or
potentially inappropriate omissions (PIO), and are avoidable if inappropriate
prescriptions or omissions are identified and prevented. Identifying PIP/PIO at
the population level through the application of PIP/PIO assessment tools to
health administrative data can provide a unique opportunity to assess the
economic burden of PIP/PIO on the healthcare system beyond medication costs which
is yet to be done. The objective of this study is to assess the economic burden
associated with PIP/PIO and to estimate the incremental costs associated with
distinct PIP/PIO in the province of Ontario. METHODS AND ANALYSIS: We will
conduct a retrospective cohort study using Ontario's health administrative
databases. Eligible patients aged 66 years and older who were prescribed at least
one medication between 1 April 2003 and 31 March 2014 (approximately 2.4 million
patients) will be included. Population attributable fraction methodology will be
used to assess the overall burden of PIP in Ontario, while regression analyses
will be used to estimate the incremental costs of having specific PIP criteria
and aid in prioritising targets for intervention. ETHICS AND DISSEMINATION: This
study was approved by the Institutional Review Board at Sunnybrook Health
Sciences Centre, Toronto, Canada. Dissemination will occur via publication,
presentation at national and international conferences, and knowledge exchange
with various stakeholders.
PMID- 29950473
TI - Use of patient-held information about medication (PHIMed) to support medicines
optimisation: protocol for a mixed-methods descriptive study.
AB - INTRODUCTION: Risks of poor information transfer across health settings are well
documented, particularly for medication. There is also increasing awareness of
the importance of greater patient activation. Patients may use various types of
patient-held information about medication (PHIMed) to facilitate medication
transfer, which may be paper or electronic. However, it is not known how PHIMed
should best be used, whether it improves patient outcomes, nor is its key 'active
ingredients' known. Discussion with patients and carers has highlighted this as a
priority for research. We aim to identify how PHIMed is used in practice,
barriers and facilitators to its use and key features of PHIMed that support
medicines optimisation in practice. METHODS AND ANALYSIS: This study will take
place in Greater London, England. We will include patients with long-term
conditions, carers and healthcare professionals. The study has four work packages
(WPs). WP1 involves qualitative interviews with healthcare professionals (n=16)
and focus groups with patients and carers (n=20), including users and non-users
of PHIMed, to study perceptions around its role, key features, barriers and
facilitators, and any unintended consequences. WP2 will involve documentary
analysis of how PHIMed is used, what is documented and read, and by whom, in a
stratified sample of 60 PHIMed users. In WP3, we will carry out a descriptive
analysis of PHIMed tools used/available, both electronic and paper, and
categorise their design and key features based on those identified in WP1/2.
Finally, in WP4, findings from WPs 1-3 will be integrated and analysed using
distributed cognition as a theoretical framework to explore how information is
recorded, transformed and propagated among different people and artefacts. ETHICS
AND DISSEMINATION: The study has National Health Service ethics approval. It will
provide initial recommendations around the present use of PHIMed to optimise
patient care for patients, carers and healthcare professionals.
PMID- 29950474
TI - Economic cost of substandard and falsified human medicines and cosmetics with
banned ingredients in Tanzania from 2005 to 2015: a retrospective review of data
from the regulatory authority.
AB - OBJECTIVE: To estimate the economic cost of substandard and falsified human
medicines and cosmetics with banned ingredients in Tanzania from 2005 to 2015.
DESIGN: A retrospective review of data. SETTING: Tanzania Food and Drugs
Authority and premises dealing with importations and distributions of
pharmaceuticals. ELIGIBILITY CRITERIA: Confiscation reports of substandard human
medicines, falsified human medicines and cosmetics with banned ingredients.
PRIMARY AND SECONDARY OUTCOME MEASURES: Quantities and costs of pharmaceutical
products, costs of transportation, storage, court cases and disposal of products.
RESULTS: The economic cost of substandard and falsified human medicines and
cosmetics with banned ingredients was estimated at US$16.2 million, that is,
value of substandard medicines US$13.7 million (84.4%), falsified medicines
US$0.1 million (1%), cosmetics with banned ingredients US$1.3 million (8%) and
other/operational costs US$1.1 million (6.6%). Some of the identified substandard
and falsified human medicines include commonly used antibiotics such as
phenoxymethylpenicillin, amoxicillin, cloxacillin and co-trimoxazole;
antimalarials such quinine, sulfadoxine-pyrimethamine, sulfamethoxypyrazine
pyrimethamine and artemether-lumefantrine; antiretroviral drugs; antipyretics and
vitamins among others. CONCLUSION: The economic cost of substandard and falsified
human medicines and cosmetics with banned ingredients represent a relatively
large loss of scarce resources for a poor country like Tanzania. We believe that
the observed increase in the quantities and the economic cost of these products
over time could partly be due to the improvement in the regulatory capacity in
terms of human resources, infrastructure and frequency of inspections.
PMID- 29950475
TI - Protocol for Meal-time Administration of Exenatide for Glycaemic Control in Type
1 Diabetes Cases (The MAG1C trial): a randomised, double-blinded, placebo
controlled trial.
AB - INTRODUCTION: Persons with type 1 diabetes require intensive insulin therapy to
achieve glycaemic control, but side effects, including hypoglycaemia and weight
gain, may reduce treatment compliance. We hypothesise that add-on treatment of
the short-acting glucagon-like peptide-1 receptor agonist, exenatide, to insulin
therapy in persons with type 1 diabetes will reduce insulin requirements,
glycaemic excursions and body weight and improve glycaemic control without
increasing the risk of hypoglycaemia. The present article describes a protocol
developed to test this hypothesis. METHODS AND ANALYSIS: One-hundred adult
persons with type 1 diabetes for more than 1 year, insufficient glycaemic control
(glycated haemoglobin A1c (HbA1c) between 58 and 86 mmol/mol) and body mass index
>22.0 kg/m2 will be randomised to either exenatide 10 ug three times per day (at
meal times) or placebo as add-on therapy to regular basal-bolus insulin treatment
for 26 weeks. Primary endpoint is change in HbA1c between the two groups at end
of treatment. Secondary endpoints include change in glycaemic excursions
(assessed by continuous glucose monitoring); insulin dose; hypoglycaemic and
adverse events; body weight, lean body and fat mass; dietary patterns; quality of
life and treatment satisfaction; cardiovascular-disease risk profile;
metabolomics; and arginine-tested plasma glucose, glucagon and C-peptide levels.
ETHICS AND DISSEMINATION: The study is approved by the Danish Medicines Agency,
the Regional Scientific Ethics Committee of the Capital Region of Denmark and the
Data Protection Agency. The study will be carried out under the surveillance and
guidance of the good clinical practice (GCP) unit at Copenhagen University
Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki
Declaration. Positive, negative as well as inconclusive results will be sought
disseminated at scientific meetings and in international peer-reviewed scientific
journals. TRIAL REGISTRATION NUMBER: NCT03017352.
PMID- 29950476
TI - Comparative safety of bowel cleansers: protocol for a systematic review and
network meta-analysis.
AB - INTRODUCTION: The US Food and Drug Administration has withdrawn the bowel
cleansing kit HalfLytely (PEG 3500) with 10 mg bisacodyl tablets due to an
increased risk of ischaemic colitis compared with the same kit with only 5 mg
bisacodyl. This is of interest in Canada given that the bowel cleansing kit Bi
Peglyte (PEG 3500) with 15 mg bisacodyl is currently approved for use. The
objective is to assess the comparative safety of various bowel cleansers with or
without bisacodyl, with a primary interest inpolyethylene glycol (PEG)-based and
sodium-picosulfate-based products. METHODS AND ANALYSIS: Given the existing
volume of the literature, the review will be conducted in two stages. Stage 1
will consist of a scoping exercise by searching MEDLINE, Embase and the Cochrane
Library (up to 21 November 2017) to identify randomised controlled trials,
quasirandomised studies and non-randomised studies in which any bowel cleanser
regimens were compared among persons undergoing colonoscopy. The outcomes will be
mapped to establish a listing of the studies and their comparisons and outcomes
currently available in the literature. From this, a data synthesis plan will be
determined. In stage 2, a systematic review with meta-analyses will be pursued,
focused on the bowel cleanser comparisons and outcomes of interest identified in
stage 1. Two reviewers will screen, extract and quality assess the articles.
Outcomes of interest include ischaemic colitis, electrolyte imbalances and their
consequences, seizures, bowel perforation and patient tolerability. If sufficient
data exist and studies are of sufficient homogeneity, network meta-analyses
(NMAs) will be performed. ETHICS AND DISSEMINATION: Ethics approval was not
necessary due to study design. Updating the safety profile of bowel cleansers
among the generally healthy population undergoing colonoscopy is pertinent given
recent approval changes. This will be the first NMA within this population.
Policy considerations may be reconsidered to minimise risk during bowel cleanser
use. PROSPERO REGISTRATION NUMBER: CRD42018084720.
PMID- 29950477
TI - Characteristics and the average 30-day and 6-month clinical outcomes of patients
hospitalised with coronary artery disease in a poor South-East Asian setting: the
first cohort from Makassar Cardiac Center, Indonesia.
AB - OBJECTIVE: To provide a detailed description of characteristics at hospital
admission and clinical outcomes at 30-day and 6-month follow-up in patients
hospitalised with coronary artery disease (CAD) in a poor South-East Asian
setting. DESIGN: Prospective observational cohort study. SETTING: From February
2013 to December 2014, in Makassar Cardiac Center, Indonesia. PARTICIPANTS: 477
patients with CAD (acute coronary syndrome and stable CAD). OUTCOME MEASURES: All
cause mortality and major adverse cardiovascular events (MACE). RESULTS: Out of
477 patients with CAD, the proportion of young age (<60 years) was 53.9% and
72.7% were male. At admission, 44.2% of patients were diagnosed with ST-segment
elevation myocardial infarction (STEMI), 38.6% with diagnosis or signs of heart
failure and 75.1% had previous hypertension. Out of 211 patients with STEMI, only
4.7% had been treated with primary percutaneous coronary intervention (PCI) and
6.2% received thrombolysis. The time lapse from symptom onset to hospital
admission was 26.8 (IQR 10.0-48.0) hours, and 19.1% of all patients had undergone
either PCI or coronary artery bypass graft. The survival rate at 6 months was
78.9%. The rates of all-cause mortality at 30 days and 6 months were 13.4% and
7.3%, respectively; the rate of composite MACE at 30 days was 26.2% and 18.0% at
6 months. CONCLUSIONS: Patients with CAD from a poor South-East Asian setting
present themselves with predominantly unstable conditions of premature CAD. These
patients show relatively severe illness, have significant time delay from symptom
onset to admission or intervention, and most do not receive the guidelines
recommended treatment. Awareness of symptoms, prompt initial management of acute
CVD, well-established infrastructures and resources both in primary and secondary
hospital for CVD should be improved to reduce the high rates of 30-day and 6
month mortality and adverse outcomes in this population.
PMID- 29950478
TI - Factors influencing early and late readmissions in Australian hospitalised
patients and investigating role of admission nutrition status as a predictor of
hospital readmissions: a cohort study.
AB - OBJECTIVES: Limited studies have identified predictors of early and late hospital
readmissions in Australian healthcare settings. Some of these predictors may be
modifiable through targeted interventions. A recent study has identified
malnutrition as a predictor of readmissions in older patients but this has not
been verified in a larger population. This study investigated what predictors are
associated with early and late readmissions and determined whether nutrition
status during index hospitalisation can be used as a modifiable predictor of
unplanned hospital readmissions. DESIGN: A retrospective cohort study. SETTING:
Two tertiary-level hospitals in Australia. PARTICIPANTS: All medical admissions
>=18 years over a period of 1 year. OUTCOMES: Primary objective was to determine
predictors of early (0-7 days) and late (8-180 days) readmissions. Secondary
objective was to determine whether nutrition status as determined by malnutrition
universal screening tool (MUST) can be used to predict readmissions. RESULTS:
There were 11 750 (44.8%) readmissions within 6 months, with 2897 (11%) early and
8853 (33.8%) late readmissions. MUST was completed in 16.2% patients and
prevalence of malnutrition during index admission was 31%. Malnourished patients
had a higher risk of both early (OR 1.39, 95% CI 1.12 to 1.73) and late
readmissions (OR 1.23, 95% CI 1.06 to 128). Weekend discharges were less likely
to be associated with both early (OR 0.81, 95% CI 0.74 to 0.91) and late
readmissions (OR 0.91, 95% CI 0.84 to 0.97). Indigenous Australians had a higher
risk of early readmissions while those living alone had a higher risk of late
readmissions. Patients >=80 years had a lower risk of early readmissions while
admission to intensive care unit was associated with a lower risk of late
readmissions. CONCLUSIONS: Malnutrition is a strong predictor of unplanned
readmissions while weekend discharges are less likely to be associated with
readmissions. Targeted nutrition intervention may prevent unplanned hospital
readmissions. TRIAL REGISTRATION: ANZCTRN 12617001362381; Results.
PMID- 29950479
TI - Retirement ages of senior UK doctors: national surveys of the medical graduates
of 1974 and 1977.
AB - OBJECTIVE: To report on retirement ages of two cohorts of senior doctors in the
latter stages of their careers. DESIGN: Questionnaires sent in 2014 to all
medical graduates of 1974 and 1977. SETTING: UK. PARTICIPANTS: 3695 UK medical
graduates. MAIN OUTCOME MEASURES: Retirement status by age at the time of the
survey and age at retirement if retired. Planned retirement ages and retirement
plans if not retired. RESULTS: Of contactable doctors, 85% responded. 43.7% of
all responding doctors had fully retired, 25.9% had 'retired and returned' for
some medical work, 18.3% had not retired and were working full-time in medicine,
10.7% had not retired and were working part-time in medicine and 1.4% were either
doing non-medical work or did not give details of their employment status. The
average actual retirement age (including those who had retired but subsequently
returned) was 59.6 years (men 59.9, women 58.9). Psychiatrists (58.3) and general
practitioners (GPs) (59.5) retired at a slightly younger age than radiologists
(60.4), surgeons (60.1) and hospital specialists (60.0). More GPs (54%) than
surgeons (26%) or hospital medical specialists (34%) were fully retired, and
there were substantial variations in retirement rates in other specialties. Sixty
three per cent of women GPs were fully retired. CONCLUSIONS: Gender and specialty
differences in retirement ages were apparent and are worthy of qualitative study
to establish underlying reasons in those specialties where earlier retirement is
more common. There is a general societal expectation that people will retire at
increasingly elderly ages; but the doctors in this national study retired
relatively young.
PMID- 29950482
TI - Art of bringing NHS data to life.
PMID- 29950480
TI - Study protocol for a multicentre, cluster randomised, superiority trial
evaluating the impact of computerised decision support, audit and feedback on
antibiotic use: the COMPuterized Antibiotic Stewardship Study (COMPASS).
AB - INTRODUCTION: Inappropriate use of antimicrobials in hospitals contributes to
antimicrobial resistance. Antimicrobial stewardship (AMS) interventions aim to
improve antimicrobial prescribing, but they are often resource and personnel
intensive. Computerised decision supportsystems (CDSSs) seem a promising tool to
improve antimicrobial prescribing but have been insufficiently studied in
clinical trials. METHODS AND ANALYSIS: The COMPuterized Antibiotic Stewardship
Study trial, is a publicly funded, open-label, cluster randomised, controlled
superiority trial which aims to determine whether a multimodal CDSS intervention
integrated in the electronic health record (EHR) reduces overall antibiotic
exposure in adult patients hospitalised in wards of two secondary and one
tertiary care centre in Switzerland compared with 'standard-of-care' AMS. Twenty
four hospital wards will be randomised 1:1 to either intervention or control,
using a 'pair-matching' approach based on baseline antibiotic use, specialty and
centre. The intervention will consist of (1) decision support for the choice of
antimicrobial treatment and duration of treatment for selected indications (based
on indication entry), (2) accountable justification for deviation from the local
guidelines (with regard to the choice of molecules and duration), (3) alerts for
self-guided re-evaluation of treatment on calendar day 4 of antimicrobial therapy
and (4) monthly ward-level feedback of antimicrobial prescribing indicators. The
primary outcome will be the difference in overall systemic antibiotic use
measured in days of therapy per admission based on administration data recorded
in the EHR over the whole intervention period (12 months), taking into account
clustering. Secondary outcomes include qualitative and quantitative antimicrobial
use indicators, economic outcomes and clinical, microbiological and patient
safety indicators. ETHICS AND DISSEMINATION: Ethics approval was obtained for all
participating sites (Comission Cantonale d'Ethique de la Recherche (CCER)2017
00454). The results of the trial will be submitted for publication in a peer
reviewed journal. Further dissemination activities will be presentations/posters
at national and international conferences. TRIAL REGISTRATION NUMBER:
NCT03120975; Pre-results.
PMID- 29950481
TI - Study protocol: Our Cultures Count, the Mayi Kuwayu Study, a national
longitudinal study of Aboriginal and Torres Strait Islander wellbeing.
AB - INTRODUCTION: Aboriginal and Torres Strait Islander peoples are Australia's first
peoples and have been connected to the land for >=65 000 years. Their enduring
cultures and values are considered critical to health and wellbeing, alongside
physical, psychological and social factors. We currently lack large-scale data
that adequately represent the experiences of Aboriginal and Torres Strait
Islander people; the absence of evidence on cultural practice and expression is
particularly striking, given its foundational importance to wellbeing. METHOD AND
ANALYSIS: Mayi Kuwayu: The National Study of Aboriginal and Torres Strait
Islander Wellbeing (Mayi Kuwayu Study) will be a large-scale, national
longitudinal study of Aboriginal and Torres Strait Islander adults, with linkage
to health-related administrative records. The baseline survey was developed
through extensive community consultation, and includes items on: cultural
practice and expression, sociodemographic factors, health and wellbeing, health
behaviours, experiences and environments, and family support and connection. The
baseline survey will be mailed to 200 000 Aboriginal and Torres Strait Islander
adults (>=16 years), yielding an estimated 16 000-40 000 participants,
supplemented through face-to-face recruitment. Follow-up surveys will be
conducted every 3-5 years, or as funding allows. The Mayi Kuwayu Study will
contribute to filling key evidence gaps, including quantifying the contribution
of cultural factors to wellbeing, alongside standard elements of health and risk.
ETHICS AND DISSEMINATION: This study has received approval from national Human
Research Ethics Committees, and from State and Territory committees, including
relevant Aboriginal and Torres Strait Islander organisations. The study was
developed and is conducted in partnership with Aboriginal and Torres Strait
Islander organisations across states and territories. It will provide an enduring
and shared infrastructure to underpin programme and policy development, based on
measures and values important to Aboriginal and Torres Strait Islander peoples.
Approved researchers can access confidentialised data and disseminate findings
according to study data access and governance protocols.
PMID- 29950483
TI - Histone arginine methylation by Prmt5 is required for lung branching
morphogenesis through repression of BMP signaling.
AB - Branching morphogenesis is essential for the successful development of a
functional lung to accomplish its gas exchange function. Although many studies
have highlighted requirements for the bone morphogenetic protein (BMP) signaling
pathway during branching morphogenesis, little is known about how BMP signaling
is regulated. Here, we report that the protein arginine methyltransferase 5
(Prmt5) and symmetric dimethylation at histone H4 arginine 3 (H4R3sme2) directly
associate with chromatin of Bmp4 to suppress its transcription. Inactivation of
Prmt5 in the lung epithelium results in halted branching morphogenesis, altered
epithelial cell differentiation and neonatal lethality. These defects are
accompanied by increased apoptosis and reduced proliferation of lung epithelium,
as a consequence of elevated canonical BMP-Smad1/5/9 signaling. Inhibition of BMP
signaling by Noggin rescues the lung branching defects of Prmt5 mutant in vitro
Taken together, our results identify a novel mechanism through which Prmt5
mediated histone arginine methylation represses canonical BMP signaling to
regulate lung branching morphogenesis.
PMID- 29950484
TI - AMP-activated protein kinase promotes epithelial-mesenchymal transition in cancer
cells through Twist1 upregulation.
AB - The developmental programme of epithelial-mesenchymal transition (EMT), involving
loss of epithelial and acquisition of mesenchymal properties, plays an important
role in the invasion-metastasis cascade of cancer cells. In the present study, we
show that activation of AMP-activated protein kinase (AMPK) using A769662 led to
a concomitant induction of EMT in multiple cancer cell types, as observed by
enhanced expression of mesenchymal markers, decrease in epithelial markers, and
increase in migration and invasion. In contrast, inhibition or depletion of AMPK
led to a reversal of EMT. Importantly, AMPK activity was found to be necessary
for the induction of EMT by physiological cues such as hypoxia and TGFbeta
treatment. Furthermore, AMPK activation increased the expression and nuclear
localization of Twist1, an EMT transcription factor. Depletion of Twist1 impaired
AMPK-induced EMT phenotypes, suggesting that AMPK might mediate its effects on
EMT, at least in part, through Twist1 upregulation. Inhibition or depletion of
AMPK also attenuated metastasis. Thus, our data underscore a central role for
AMPK in the induction of EMT and in metastasis, suggesting that strategies
targeting AMPK might provide novel approaches to curb cancer spread.
PMID- 29950486
TI - Effects of Repeated Binge Drinking on Blood Pressure Levels and Other
Cardiovascular Health Metrics in Young Adults: National Health and Nutrition
Examination Survey, 2011-2014.
AB - BACKGROUND: Binge drinking prevalence rates are highest in young adults; however,
little is known about the effects of binge drinking on blood pressure (BP) and
other cardiovascular health metrics in individuals between 18 and 45 years of
age. The aim of this study was to determine the effects of regular binge drinking
on BP, lipid and glucose levels and to determine if there were differences in
these associations between men and women. METHODS AND RESULTS: We analyzed data
from NHANES (the US National Health and Nutrition Examination Survey) for men and
women 18 to 45 years old who were non-binge drinkers, binge drank 1 to 12 times,
or binge drank >12 times in the past year. After controlling for diet and
physical activity, both categories of men binge drinkers compared with non-binge
drinkers had higher systolic BP (121.8 and 119.0 mm Hg versus 117.5 mm Hg) and
total cholesterol (215.5 and 217.9 mg/dL versus 207.8 mg/dL) values. There were
no effects of binge drinking on systolic BP or total cholesterol in women. Binge
drinking in men and women was associated with higher high-density lipoprotein
cholesterol values. The effects of binge drinking on glucose parameters in men
and women were variable. CONCLUSIONS: Compared with young adult women, repeated
binge drinking in men was associated with an elevated systolic BP, and greater
frequency of binge drinking in men was associated with a more unfavorable lipid
profile. In young adults with elevated systolic BP, practitioners should consider
the possible role of binge drinking and address the importance of reducing
alcohol intake as an important cardiovascular risk reduction strategy.
PMID- 29950485
TI - Sex-Specific Associations Between Alcohol Consumption and Incidence of
Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies.
AB - BACKGROUND: Although it is well established that heavy alcohol consumption
increases the risk of hypertension, the risk associated with low levels of
alcohol intake in men and women is unclear. METHODS AND RESULTS: We searched
Medline and Embase for original cohort studies on the association between average
alcohol consumption and incidence of hypertension in people without hypertension.
Random-effects meta-analyses and metaregressions were conducted. Data from 20
articles with 361 254 participants (125 907 men and 235 347 women) and 90 160
incident cases of hypertension (32 426 men and 57 734 women) were included. In
people drinking 1 to 2 drinks/day (12 g of pure ethanol per drink), incidence of
hypertension differed between men and women (relative riskwomen vs men=0.79; 95%
confidence interval, 0.67-0.93). In men, the risk for hypertension in comparison
with abstainers was relative risk=1.19 (1.07-1.31; I2=59%), 1.51 (1.30-1.76), and
1.74 (1.35-2.24) for consumption of 1 to 2, 3 to 4, and 5 or more standard drinks
per day, respectively. In women, there was no increased risk for 1 to 2
drinks/day (relative risk=0.94; 0.88-1.01; I2=73%), and an increased risk for
consumption beyond this level (relative risk=1.42; 1.22-1.66). CONCLUSIONS: Any
alcohol consumption was associated with an increase in the risk for hypertension
in men. In women, there was no risk increase for consumption of 1 to 2 drinks/day
and an increased risk for higher consumption levels. We did not find evidence for
a protective effect of alcohol consumption in women, contrary to earlier meta
analyses.
PMID- 29950487
TI - Alcohol Consumption, Hypertension, and Cardiovascular Health Across the Life
Course: There Is No Such Thing as a One-Size-Fits-All Approach.
PMID- 29950488
TI - Highlights From the American Heart Association's EPI|LIFESTYLE 2018 Scientific
Sessions.
PMID- 29950490
TI - Macchiarini case: seven researchers are guilty of scientific misconduct, rules
Karolinska's president.
PMID- 29950489
TI - Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in
patients with a documented penicillin allergy: population based matched cohort
study.
AB - OBJECTIVE: To evaluate the relation between penicillin allergy and development of
meticillin resistant Staphylococcus aureus (MRSA) and C difficile. DESIGN:
Population based matched cohort study. SETTING: United Kingdom general practice
(1995-2015). PARTICIPANTS: 301 399 adults without previous MRSA or C difficile
enrolled in the Health Improvement Network database: 64 141 had a penicillin
allergy and 237 258 comparators matched on age, sex, and study entry time. MAIN
OUTCOME MEASURES: The primary outcome was risk of incident MRSA and C difficile.
Secondary outcomes were use of beta lactam antibiotics and beta lactam
alternative antibiotics. RESULTS: Among 64 141 adults with penicillin allergy and
237 258 matched comparators, 1365 developed MRSA (442 participants with
penicillin allergy and 923 comparators) and 1688 developed C difficile (442
participants with penicillin allergy and 1246 comparators) during a mean 6.0
years of follow-up. Among patients with penicillin allergy the adjusted hazard
ratio for MRSA was 1.69 (95% confidence interval 1.51 to 1.90) and for C
difficile was 1.26 (1.12 to 1.40). The adjusted incidence rate ratios for
antibiotic use among patients with penicillin allergy were 4.15 (95% confidence
interval 4.12 to 4.17) for macrolides, 3.89 (3.66 to 4.12) for clindamycin, and
2.10 (2.08 to 2.13) for fluoroquinolones. Increased use of beta lactam
alternative antibiotics accounted for 55% of the increased risk of MRSA and 35%
of the increased risk of C difficile. CONCLUSIONS: Documented penicillin allergy
was associated with an increased risk of MRSA and C difficile that was mediated
by the increased use of beta lactam alternative antibiotics. Systematically
addressing penicillin allergies may be an important public health strategy to
reduce the incidence of MRSA and C difficile among patients with a penicillin
allergy label.
PMID- 29950493
TI - Helping smokers to quit.
PMID- 29950491
TI - Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up
regulation of Igf2 in nephron progenitor cells.
AB - Loss of function of the DIS3L2 exoribonuclease is associated with Wilms tumor and
the Perlman congenital overgrowth syndrome. LIN28, a Wilms tumor oncoprotein,
triggers the DIS3L2-mediated degradation of the precursor of let-7, a microRNA
that inhibits Wilms tumor development. These observations have led to speculation
that DIS3L2-mediated tumor suppression is attributable to let-7 regulation. Here
we examine new DIS3L2-deficient cell lines and mouse models, demonstrating that
DIS3L2 loss has no effect on mature let-7 levels. Rather, analysis of Dis3l2-null
nephron progenitor cells, a potential cell of origin of Wilms tumors, reveals up
regulation of Igf2, a growth-promoting gene strongly associated with Wilms
tumorigenesis. These findings nominate a new potential mechanism underlying the
pathology associated with DIS3L2 deficiency.
PMID- 29950494
TI - Dural arteriovenous fistula presenting with acute subdural haematoma showing
impending cerebral herniation.
AB - A dural arteriovenous fistula (DAVF) presenting with acute subdural haematoma
(ASDH), which were not related to head injury, is rare. A 61-year-old woman was
transported by ambulance because of deterioration of consciousness. On admission,
she was comatose with anisocoria. Emergent CT demonstrated a severe midline shift
associated with a left ASDH and an additional left occipital intracerebral
haematoma, both of which had no continuity with each other. MRI showed flow void
signs in the left occipital lobe. Because of the impending cerebral herniation,
an emergent evacuation of the ASDH and external decompression was performed.
Subsequent evaluation revealed a DAVF at the left occipital convexity near the
confluence with retrograde leptomeningeal venous reflux and venous ectasia
(Cognard type III DAVF). The patient underwent endovascular treatment for the
DAVF involving transarterial embolisation using coils and N-butyl cyanoacrylate
with complete obliteration. Her further clinical course was uneventful and
discharged after cranioplasty.
PMID- 29950492
TI - The C9orf72-interacting protein Smcr8 is a negative regulator of autoimmunity and
lysosomal exocytosis.
AB - While a mutation in C9ORF72 is the most common genetic contributor to amyotrophic
lateral sclerosis (ALS), much remains to be learned concerning the function of
the protein normally encoded at this locus. To elaborate further on functions for
C9ORF72, we used quantitative mass spectrometry-based proteomics to identify
interacting proteins in motor neurons and found that its long isoform complexes
with and stabilizes SMCR8, which further enables interaction with WDR41. To study
the organismal and cellular functions for this tripartite complex, we generated
Smcr8 loss-of-function mutant mice and found that they developed phenotypes also
observed in C9orf72 loss-of-function animals, including autoimmunity. Along with
a loss of tolerance for many nervous system autoantigens, we found increased
lysosomal exocytosis in Smcr8 mutant macrophages. In addition to elevated surface
Lamp1 (lysosome-associated membrane protein 1) expression, we also observed
enhanced secretion of lysosomal components-phenotypes that we subsequently
observed in C9orf72 loss-of-function macrophages. Overall, our findings
demonstrate that C9ORF72 and SMCR8 have interdependent functions in suppressing
autoimmunity as well as negatively regulating lysosomal exocytosis-processes of
potential importance to ALS.
PMID- 29950495
TI - New headaches with normal inflammatory markers: an early atypical presentation of
giant cell arteritis.
AB - An 80-year-old man presented repeatedly to his general practitioner with 3 months
of unexplained persistent frontal headaches. CT head revealed no diagnosis. His
dentist diagnosed his co-existing jaw pain as bruxism. Three months later, the
patient happened to attend a routine ophthalmology follow-up appointment. During
this routine appointment, features of giant cell arteritis (GCA) including
worrying visual complications were first noted. His inflammatory markers (C
reactive protein and erythrocyte sedimentation rate) were not significantly
raised-contrary to the norm. A temporal artery ultrasound and biopsy were
performed, in light of the history. This confirmed GCA. He was commenced on high
dose oral prednisolone and was managed by ophthalmology and rheumatology. At 4
weeks, symptoms resolved with no permanent visual loss despite a prolonged
initial symptomatic period. Multiple symptomatic presentations to different
specialties should therefore alert clinicians to a unifying diagnosis, for
example, vasculitis. Serious illnesses may present with severe symptoms despite
normal screening investigations.
PMID- 29950496
TI - Correction: Primary malignant melanoma of the ascending colon.
PMID- 29950497
TI - Possible SAMe-induced mania.
AB - This paper describes a patient who presented with mania with psychotic features
in the context of concomitant use of S-adenosyl-L-methionine (SAMe) and selective
serotonin reuptake inhibitor (SSRI). The aim of this case report is to provide
medical practitioners with a greater awareness of the possibility of a psychotic
episode and/or mania manifesting with concurrent use of SAMe and SSRI.
PMID- 29950498
TI - Intravenous immunoglobulin for severe thrombocytopenia in secondary dengue.
AB - A 30-year-old woman with severe dengue presented on the sixth day of her illness
with life-threatening thrombocytopenia, refractory to multiple platelet
transfusions. Dengue IgM antibody and the non-structural-1 antigen tests as of
day 3 were negative. The IgG antibody against the same was positive, suggesting a
past episode of dengue. Since she had a history of menorrhagia prior to the
current illness, a working diagnosis of idiopathic thrombocytopenic purpura was
made, for which intravenous immunoglobulin (IVIg) was administered that led to a
rapid rise in the platelet count with no adverse events. Subsequently, dengue IgM
antibody repeated on day 6 came back positive, confirming dengue. This case
report re-emphasises the potential use of IVIg in patients with severe
thrombocytopenia in dengue.
PMID- 29950499
TI - Cloudy Cornea with Arcus Juvenilis in a Case of Dense Deposit Disease.
AB - A 25-year-old male patient presented with complaints of blurred vision in both
eyes since 2 years. The patient was a known case of nephrotic syndrome with
dyslipidaemia for which he was on diuretics and lipid-lowering agents for 3
years. On examination, his visual acuity was 6/9 in both eyes with cloudy cornea
and arcus juvenilis. Fundus examination was within normal limits. On systemic
work-up, his lipid profile was deranged with increased serum total cholesterol,
very low density lipoprotein, low density lipoprotein and triglyceride. The serum
high density lipoprotein was decreased. Renal function test revealed elevated
serum creatinine with significant proteinuria. Renal biopsy was suggestive of
dense deposit disease on immunofluorescence and transmission electron microscopy.
Ocular manifestation of dense deposit disease is characterised by retinal drusen,
pigmentary atrophy, choroidal neovascular membrane and atypical serous
retinopathy. To the best of our knowledge, anterior segment changes in dense
deposit disease has not been reported. This is the first case reporting cloudy
cornea with arcus juvenilis in a case of dense deposit disease.
PMID- 29950500
TI - Perioperative continuous glucose monitoring in a preterm infant.
AB - Surgery in the neonatal period presents challenges, especially in preterm infants
weighing <1 kg. Their small size, minimal reserves and physiological immaturity
means attention to detail and careful monitoring is critical to avoid
cardiovascular instability; maintaining fluid balance and metabolic stability is
also problematic due to often limited vascular access and small blood volumes.
Developments in technology have meant that cardiovascular parameters such as
heart rate, blood pressure and oxygen saturations are all routinely and
continuously monitored before and during surgery.We have been exploring the role
of continuous glucose monitoring (CGM) for metabolic monitoring and management of
glucose control in very preterm infants (24-32 weeks gestation). In this paper,
we report on a preterm infant who uniquely underwent surgery while wearing a
continuous glucose monitor, blinded to the clinical team. This case highlights
the metabolic vulnerability of these babies and a possible role for real-time CGM
during surgical procedures.
PMID- 29950501
TI - Pyopericardium presenting with echocardiographic features of pericardial
tamponade in an elderly man.
AB - A 72-year-old Chinese man presented with mild symptoms of heart failure.
Transthoracic echocardiography showed signs of cardiac tamponade though
clinically he was relatively well. The option of pericardiocentesis was not
carried out due to a narrow window for aspiration with only a thin layer of
effusion seen surrounding the apex and right ventricle on subcostal
view.Pericardial window was done via a left anterolateral thoracotomy.
Intraoperatively, 500 cm3 of purulent fluid was drained. Microbiology screens
were all negative. We present the atypical clinical course of this elderly man
presenting with a large pyopericardium.
PMID- 29950502
TI - Brown-Vialetto-Van Laere syndrome: a novel diagnosis to a common presentation.
AB - Brown-Vialetto-Van Laere syndrome (BVVLS) or riboflavin transporter deficiency
(OMIM 211530) is a rare treatable autosomal recessive neurodegenerative disorder.
This condition is associated with progressive pontobulbar palsy. We describe the
clinical course of a 16-month-old boy with BVVLS and a novel homozygous mutation
from Pakistan. Our patient presented with stridor and respiratory insufficiency.
Hearing loss which is the most common sign of this condition was absent, making
it an unusual presentation of BVVLS. His examination revealed ptosis and tongue
fasciculation. His riboflavin receptor mutational analysis showed the homozygous
mutation in the SLC52A3 gene. Per oral riboflavin was administered, and
subsequently, he was able to be weaned off the ventilator. Now the child is
improving and attaining developmental milestones.
PMID- 29950503
TI - Craniovertebral junction cord compression due to neurofibroma.
PMID- 29950504
TI - Postsynaptic FMRP Regulates Synaptogenesis In Vivo in the Developing Cochlear
Nucleus.
AB - A global loss of the fragile X mental retardation protein (FMRP; encoded by the
Fmr1 gene) leads to sensory dysfunction and intellectual disabilities. One
underlying mechanism of these phenotypes is structural and functional deficits in
synapses. Here, we determined the autonomous function of postsynaptic FMRP in
circuit formation, synaptogenesis, and synaptic maturation. In normal cochlea
nucleus, presynaptic auditory axons form large axosomatic endbulb synapses on
cell bodies of postsynaptic bushy neurons. In ovo electroporation of drug
inducible Fmr1-shRNA constructs produced a mosaicism of FMRP expression in
chicken (either sex) bushy neurons, leading to reduced FMRP levels in
transfected, but not neighboring nontransfected, neurons. Structural analyses
revealed that postsynaptic FMRP reduction led to smaller size and abnormal
morphology of individual presynaptic endbulbs at both early and later
developmental stages. We further examined whether FMRP reduction affects
dendritic development, as a potential mechanism underlying defective endbulb
formation. Normally, chicken bushy neurons grow extensive dendrites at early
stages and retract these dendrites when endbulbs begin to form. Neurons
transfected with Fmr1 shRNA exhibited a remarkable delay in branch retraction,
failing to provide necessary somatic surface for timely formation and growth of
large endbulbs. Patch-clamp recording verified functional consequences of
dendritic and synaptic deficits on neurotransmission, showing smaller amplitudes
and slower kinetics of spontaneous and evoked EPSCs. Together, these data
demonstrate that proper levels of postsynaptic FMRP are required for timely
maturation of somatodendritic morphology, a delay of which may affect
synaptogenesis and thus contribute to long-lasting deficits of excitatory
synapses.SIGNIFICANCE STATEMENT Fragile X mental retardation protein (FMRP)
regulates a large variety of neuronal activities. A global loss of FMRP affects
neural circuit development and synaptic function, leading to fragile X syndrome
(FXS). Using temporally and spatially controlled genetic manipulations, this
study provides the first in vivo report that autonomous FMRP regulates multiple
stages of dendritic development, and that selective reduction of postsynaptic
FMRP leads to abnormal development of excitatory presynaptic terminals and
compromised neurotransmission. These observations demonstrate secondary influence
of developmentally transient deficits in neuronal morphology and connectivity to
the development of long-lasting synaptic pathology in FXS.
PMID- 29950506
TI - David Oliver: England's social care models harm the poorest areas.
PMID- 29950507
TI - Vulnerability as practice in diagnosing multiple conditions.
AB - The paper contributes to contemporary understandings of vulnerability by
expanding their scope with an understanding of vulnerability as generated through
institutionalised practices. The argument draws on experiential accounts of
navigating the practices of diagnosis by people living with multiple conditions
of ill-health and disability. Vulnerability as a concept is used widely across
different domains and conveys a multitude of meanings. Contemporary biomedicine,
and its associated health systems and services, understands vulnerability mostly
as inherent to particular physical and mental bodily conditions that put people
at risk of ill-health or emotionally fragility. This may combine with a more
epidemiological understanding of vulnerability as the experience of certain
population groups subject to entrenched structural inequalities. Philosophers and
feminists have argued that vulnerability is a universal experience of being human
while political commentators have explored its potential as a resource for
resistance and action. Diagnosis within medicine and psychiatry has been the
subject of extensive social analysis, critique and activism. The paper draws on
first-hand experiential accounts collected through face-to-face interviews with
people living with multiple conditions about their experiences of diagnosis,
mostly at the primary care level. We identify five aspects to diagnostic practice
that are harmful and exacerbate the experience of vulnerability: temporal
sequencing; diagnostic authority; medical specialisation; strategic symptom
selection; medical isolation. However, these diagnostic practices are not best
understood only in terms of the power asymmetries inherent to the medical
consultation, but are embedded into the very institution of diagnosis. The paper
thus proposes a combined approach to vulnerability that recognises it as a
universal condition of humanity but one that becomes animated or amplified for
some bodies, through their own inherent incapacities or the external structures
of inequality, and through the practices of medicine as situated in particular
times and places.
PMID- 29950505
TI - The Claudin-like Protein HPO-30 Is Required to Maintain LAChRs at the C. elegans
Neuromuscular Junction.
AB - Communications across chemical synapses are primarily mediated by
neurotransmitters and their postsynaptic receptors. There are diverse molecular
systems to localize and regulate the receptors at the synapse. Here, we identify
HPO-30, a member of the claudin superfamily of membrane proteins, as a positive
regulator for synaptic localization of levamisole-dependent AChRs (LAChRs) at the
Caenorhabditis elegans neuromuscular junction (NMJ). The HPO-30 protein localizes
at the NMJ and shows genetic and physical association with the LAChR subunits LEV
8, UNC-29, and UNC-38. Using genetic and electrophysiological assays in the
hermaphrodite C. elegans, we demonstrate that HPO-30 functions through Neuroligin
at the NMJ to maintain postsynaptic LAChR levels at the synapse. Together, this
work suggests a novel function for a tight junction protein in maintaining normal
receptor levels at the NMJ.SIGNIFICANCE STATEMENT Claudins are a large
superfamily of membrane proteins. Their role in maintaining the functional
integrity of tight junctions has been widely explored. Our experiments suggest a
critical role for the claudin-like protein, HPO-30, in maintaining synaptic
levamisole-dependent AChR (LAChR) levels. LAChRs contribute to <20% of the
acetylcholine-mediated conductance in adult Caenorhabditis elegans; however, they
play a significant functional role in worm locomotion. This study provides a new
perspective in the study of LAChR physiology.
PMID- 29950508
TI - Anti-Insulin B Cells Are Poised for Antigen Presentation in Type 1 Diabetes.
AB - Early breaches in B cell tolerance are central to type 1 diabetes progression in
mouse and man. Conventional BCR transgenic mouse models (VH125.Tg NOD) reveal the
power of B cell specificity to drive disease as APCs. However, in conventional
fixed IgM models, comprehensive assessment of B cell development is limited. To
provide more accurate insight into the developmental and functional fates of anti
insulin B cells, we generated a new NOD model (VH125SDNOD) in which anti-insulin
VDJH125 is targeted to the IgH chain locus to generate a small (1-2%) population
of class switch-competent insulin-binding B cells. Tracking of this rare
population in a polyclonal repertoire reveals that anti-insulin B cells are
preferentially skewed into marginal zone and late transitional subsets known to
have increased sensitivity to proinflammatory signals. Additionally, IL-10
production, characteristic of regulatory B cell subsets, is increased. In
contrast to conventional models, class switch-competent anti-insulin B cells
proliferate normally in response to mitogenic stimuli but remain functionally
silent for insulin autoantibody production. Diabetes development is accelerated,
which demonstrates the power of anti-insulin B cells to exacerbate disease
without differentiation into Ab-forming or plasma cells. Autoreactive T cell
responses in VH125SDNOD mice are not restricted to insulin autoantigens, as
evidenced by increased IFN-gamma production to a broad array of diabetes
associated epitopes. Together, these results independently validate the
pathogenic role of anti-insulin B cells in type 1 diabetes, underscore their
diverse developmental fates, and demonstrate the pathologic potential of coupling
a critical beta cell specificity to predominantly proinflammatory Ag-presenting B
cell subsets.
PMID- 29950510
TI - BMA votes to oppose Brexit "as a whole" and calls for public final say on deal.
PMID- 29950509
TI - Foxo3 Promotes Apoptosis of B Cell Receptor-Stimulated Immature B Cells, Thus
Limiting the Window for Receptor Editing.
AB - Central tolerance checkpoints are critical for the elimination of autoreactive B
cells and the prevention of autoimmunity. When autoreactive B cells encounter
their Ag at the immature B cell stage, BCR cross-linking induces receptor
editing, followed by apoptosis if edited cells remain autoreactive. Although the
transcription factor Foxo1 is known to promote receptor editing, the role of the
related factor Foxo3 in central B cell tolerance is poorly understood. We find
that BCR-stimulated immature B cells from Foxo3-deficient mice demonstrate
reduced apoptosis compared with wild type cells. Despite this, Foxo3-/- mice do
not develop increased autoantibodies. This suggests that the increased survival
of Foxo3-/- immature B cells allows additional rounds of receptor editing,
resulting in more cells "redeeming" themselves by becoming nonautoreactive.
Indeed, increased Iglambda usage and increased recombining sequence recombination
among Iglambda-expressing cells were observed in Foxo3-/- mice, indicative of
increased receptor editing. We also observed that deletion of high-affinity
autoreactive cells was intact in the absence of Foxo3 in the anti-hen egg
lysozyme (HEL)/membrane-bound HEL model. However, Foxo3 levels in B cells from
systemic lupus erythematosus (SLE) patients were inversely correlated with
disease activity and reduced in patients with elevated anti-dsDNA Abs. Although
this is likely due in part to increased B cell activation in these SLE patients,
it is also possible that low-affinity B cells that remain autoreactive after
editing may survive inappropriately in the absence of Foxo3 and become activated
to secrete autoantibodies in the context of other SLE-associated defects.
PMID- 29950511
TI - The relative fitness of drug-resistant Mycobacterium tuberculosis: a modelling
study of household transmission in Peru.
AB - The relative fitness of drug-resistant versus susceptible bacteria in an
environment dictates resistance prevalence. Estimates for the relative fitness of
resistant Mycobacterium tuberculosis (Mtb) strains are highly heterogeneous and
mostly derived from in vitro experiments. Measuring fitness in the field allows
us to determine how the environment influences the spread of resistance. We
designed a household structured, stochastic mathematical model to estimate the
fitness costs associated with multidrug resistance (MDR) carriage in Mtb in Lima,
Peru during 2010-2013. By fitting the model to data from a large prospective
cohort study of TB disease in household contacts, we estimated the fitness,
relative to susceptible strains with a fitness of 1, of MDR-Mtb to be 0.32 (95%
credible interval: 0.15-0.62) or 0.38 (0.24-0.61), if only transmission or
progression to disease, respectively, was affected. The relative fitness of MDR
Mtb increased to 0.56 (0.42-0.72) when the fitness cost influenced both
transmission and progression to disease equally. We found the average relative
fitness of MDR-Mtb circulating within households in Lima, Peru during 2010-2013
to be significantly lower than concurrent susceptible Mtb If these fitness levels
do not change, then existing TB control programmes are likely to keep MDR-TB
prevalence at current levels in Lima, Peru.
PMID- 29950512
TI - Estimating the distance to an epidemic threshold.
AB - The epidemic threshold of the susceptible-infected-recovered model is a boundary
separating parameters that permit epidemics from those that do not. This
threshold corresponds to parameters where the system's equilibrium becomes
unstable. Consequently, we use the average rate at which deviations from the
equilibrium shrink to define a distance to this threshold. However, the vital
dynamics of the host population may occur slowly even when transmission is far
from threshold levels. Here, we show analytically how such slow dynamics can
prevent estimation of the distance to the threshold from fluctuations in the
susceptible population. Although these results are exact only in the limit of
long-term observation of a large system, simulations show that they still provide
useful insight into systems with a range of population sizes, environmental noise
and observation schemes. Having established some guidelines about when estimates
are accurate, we then illustrate how multiple distance estimates can be used to
estimate the rate of approach to the threshold. The estimation approach is
general and may be applicable to zoonotic pathogens such as Middle East
respiratory syndrome-related coronavirus (MERS-CoV) as well as vaccine
preventable diseases like measles.
PMID- 29950513
TI - Flying in reverse: kinematics and aerodynamics of a dragonfly in backward free
flight.
AB - In this study, we investigated the backward free flight of a dragonfly,
accelerating in a flight path inclined to the horizontal. The wing and body
kinematics were reconstructed from the output of three high-speed cameras using a
template-based subdivision surface reconstruction method, and numerical
simulations using an immersed boundary flow solver were conducted to compute the
forces and visualize the flow features. During backward flight, the dragonfly
maintained an upright body posture of approximately 90 degrees relative to the
horizon. The upright body posture was used to reorient the stroke plane and the
flight force in the global frame; a mechanism known as 'force vectoring' which
was previously observed in manoeuvres of other flying animals. In addition to
force vectoring, we found that while flying backward, the dragonfly flaps its
wings with larger angles of attack in the upstroke (US) when compared with
forward flight. Also, the backward velocity of the body in the upright position
enhances the wings' net velocity in the US. The combined effect of the angle of
attack and wing net velocity yields large aerodynamic force generation in the US,
with the average magnitude of the force reaching values as high as two to three
times the body weight. Corresponding to these large forces was the presence of a
strong leading edge vortex (LEV) at the onset of US which remained attached up
until wing reversal. Finally, wing-wing interaction was found to enhance the
aerodynamic performance of the hindwings (HW) during backward flight. Vorticity
from the forewings' trailing edge fed directly into the HW LEV to increase its
circulation and enhance force production.
PMID- 29950514
TI - Exploring the intrinsic behaviour of multisite phosphorylation systems as part of
signalling pathways.
AB - Multisite phosphorylation is a basic way of chemically encoding substrate
function and a recurring feature of cell signalling pathways. A number of studies
have explored information processing characteristics of multisite
phosphorylation, through studies of the intrinsic kinetics. Many of these studies
focus on the module in isolation. In this paper, we build a bridge to connect the
behaviour of multisite modification in isolation to that as part of pathways. We
study the effect of activation of the enzymes (which are basic ways in which the
module may be regulated), as well the effects of the modified substrates being
involved in further modifications or exiting reaction compartments. We find that
these effects can induce multiple kinds of transitions, including to behaviour
not seen intrinsically in the multisite modification module. We then build on
these insights to investigate how these multisite modification systems can be
tuned by enzyme activation to realize a range of information processing outcomes
for the design of synthetic phosphorylation circuits. Connecting the complexity
of multisite modification kinetics, with the pathways in which they are embedded,
serves as a basis for teasing out many aspects of their interaction, providing
insights of relevance in systems biology, synthetic biology/chemistry and
chemical information processing.
PMID- 29950515
TI - Induction of zonal-specific cellular morphology and matrix synthesis for
biomimetic cartilage regeneration using hybrid scaffolds.
AB - Cartilage is anisotropic in nature and organized into distinct zones. Our goal
was to develop zonal-specific three-dimensional hybrid scaffolds which could
induce the generation of zonal-specific cellular morphology and extracellular
matrix (ECM) composition. The superficial and middle zones comprised two layers
of hyaluronic acid (HA) hydrogel which enveloped specifically orientated or
randomly arranged polylactic acid nanofibre meshes. The deep zone comprised a HA
hydrogel with multiple vertical channels. Primary bovine chondrocytes were seeded
into the individual zonal scaffolds, cultured for 14 days and then the ECM was
analysed. The aligned nanofibre mesh used in the superficial zone induced an
elongated cell morphology, lower glycosaminoglycan (GAG) and collagen II
production, and higher cell proliferation and collagen I production than the
cells in the middle zone scaffold. Within the middle zone scaffold, which
comprised a randomly orientated nanofibre mesh, the cells were clustered and
expressed more collagen II. The deep zone scaffold induced the highest GAG
production, the lowest cell proliferation and the lowest collagen I expression of
the three zones. Assembling the three zones and stabilizing the arrangement with
a HA hydrogel generated aligned, randomly aggregated and columnar cells in the
superficial, middle and deep zones. This study presents a method to induce zonal
specific chondrocyte morphology and ECM production.
PMID- 29950516
TI - Fabrication of optimized skin biomimics for improved interfacial retention of
cosmetic emulsions.
AB - Retention of hydrophobic active agents on human skin following the use of skin
care formulations is an important indication of the performance of the deposited
product. We have developed a novel system which replicates the interaction
between human skin and a cosmetic emulsion to systematically establish and
characterize the key parameters driving the retention process at the interface.
This included a comprehensive study of the skin's biology and physical properties
which influenced the process, the fabrication of advanced, improved skin
biomimics, the formulation of a cosmetic model-system emulsion, comprising a
hydrophobic active agent i.e. petrolatum, commonly used in cosmetic products, the
development of a dedicated and highly consistent deposition rig with a
corresponding cleaning set-up and the systematic characterization of retention
processes on the developed mimics. This study further explores the interplay of
petrolatum with skin biomimics and studies the mechanisms that give rise to
improved interfacial retention. Petrolatum has been found to create an occlusive
layer on the skin mimic, displaying high coverage from emulsion formulations. The
large particle size emulsions yielded improved retention on the developed skin
biomimics due to the microstructure of the emulsion and the counter effect of the
surfactant.
PMID- 29950517
TI - Resurrection science.
PMID- 29950519
TI - Medical students need better mental health support from universities, says BMA.
PMID- 29950518
TI - Identification and removal of sequencing artifacts produced by mispriming during
reverse transcription in multiple RNA-seq technologies.
AB - The quality of RNA sequencing data relies on specific priming by the primer used
for reverse transcription (RT-primer). Nonspecific annealing of the RT-primer to
the RNA template can generate reads with incorrect cDNA ends and can cause
misinterpretation of data (RT mispriming). This kind of artifact in RNA-seq based
technologies is underappreciated and currently no adequate tools exist to
computationally remove them from published data sets. We show that mispriming can
occur with as little as two bases of complementarity at the 3' end of the primer
followed by intermittent regions of complementarity. We also provide a
computational pipeline that identifies cDNA reads produced from RT mispriming,
allowing users to filter them out from any aligned data set. Using this analysis
pipeline, we identify thousands of mispriming events in a dozen published data
sets from diverse technologies including short RNA-seq, total/mRNA-seq, HITS
CLIP, and GRO-seq. We further show how RT mispriming can lead to
misinterpretation of data. In addition to providing a solution to computationally
remove RT-misprimed reads, we also propose an experimental solution to completely
avoid RT-mispriming by performing RNA-seq using thermostable group II intron
derived reverse transcriptase (TGIRT-seq).
PMID- 29950520
TI - Mental health benefits of interactions with nature in children and teenagers: a
systematic review.
AB - BACKGROUND: It is commonly believed that nature has positive impacts on
children's health, including physical, mental and social dimensions. This review
focuses on how accessibility to, exposure to and engagement with nature affects
the mental health of children and teenagers. METHODS: Ten academic databases were
used to systematically search and identify primary research papers in English or
French from 1990 to 1 March 2017. Papers were included for review based on their
incorporation of nature, children and teenagers (0-18 years), quantitative
results and focus on mental health. RESULTS: Of the 35 papers included in the
review, the majority focused on emotional well-being and attention deficit
disorder/hyperactivity disorder. Other outcome measures included overall mental
health, self-esteem, stress, resilience, depression and health-related quality of
life. About half of all reported findings revealed statistically significant
positive relationships between nature and mental health outcomes and almost half
reported no statistical significance. CONCLUSIONS: Findings support the
contention that nature positively influences mental health; however, in most
cases, additional research with more rigorous study designs and objective
measures of both nature and mental health outcomes are needed to confirm
statistically significant relationships. Existing evidence is limited by the
cross-sectional nature of most papers.
PMID- 29950521
TI - A flow cytometry-based in vitro assay reveals that formation of apolipoprotein E
(ApoE)-amyloid beta complexes depends on ApoE isoform and cell type.
AB - Apolipoprotein E (ApoE) is a secreted apolipoprotein with three isoforms, E2, E3,
and E4, that binds to lipids and facilitates their transport in the extracellular
environment of the brain and the periphery. The E4 allele is a major genetic risk
factor for the sporadic form of Alzheimer's disease (AD), and studies of human
brain and mouse models have revealed that E4 significantly exacerbates the
deposition of amyloid beta (Abeta). It has been suggested that this deposition
could be attributed to the formation of soluble ApoE isoform-specific ApoE-Abeta
complexes. However, previous studies have reported conflicting results regarding
the directionality and strength of those interactions. In this study, using a
series of flow cytometry assays that maintain the physiological integrity of ApoE
Abeta complexes, we systematically assessed the association of Abeta with ApoE2,
E3, or E4. We used ApoE secreted from HEK cells or astrocytes overexpressing ApoE
fused with a GFP tag. As a source of soluble Abeta peptide, we used synthetic
Abeta40 or Abeta42 or physiological Abeta secreted from CHO cell lines
overexpressing WT or V717F variant amyloid precursor protein (APP). We observed
significant interactions between the different ApoE isoforms and Abeta, with E4
interacting with Abeta more strongly than the E2 and E3 isoforms. We also found
subtle differences depending on the Abeta type and the ApoE-producing cell type.
In conclusion, these results indicate that the strength of the ApoE-Abeta
association depends on the source of Abeta or ApoE.
PMID- 29950522
TI - Targeting TRAF6 E3 ligase activity with a small-molecule inhibitor combats
autoimmunity.
AB - Constitutive NF-kappaB signaling represents a hallmark of chronic inflammation
and autoimmune diseases. The E3 ligase TNF receptor-associated factor 6 (TRAF6)
acts as a key regulator bridging innate immunity, pro-inflammatory cytokines, and
antigen receptors to the canonical NF-kappaB pathway. Structural analysis and
point mutations have unraveled the essential role of TRAF6 binding to the E2
conjugating enzyme ubiquitin-conjugating enzyme E2 N (Ubc13 or UBE2N) to generate
Lys63-linked ubiquitin chains for inflammatory and immune signal propagation.
Genetic mutations disrupting TRAF6-Ubc13 binding have been shown to reduce TRAF6
activity and, consequently, NF-kappaB activation. However, to date, no small
molecule modulator is available to inhibit the TRAF6-Ubc13 interaction and
thereby counteract NF-kappaB signaling and associated diseases. Here, using a
high-throughput small-molecule screening approach, we discovered an inhibitor of
the TRAF6-Ubc13 interaction that reduces TRAF6-Ubc13 activity both in vitro and
in cells. We found that this compound, C25-140, impedes NF-kappaB activation in
various immune and inflammatory signaling pathways also in primary human and
murine cells. Importantly, C25-140 ameliorated inflammation and improved disease
outcomes of autoimmune psoriasis and rheumatoid arthritis in preclinical in vivo
mouse models. Hence, the first-in-class TRAF6-Ubc13 inhibitor C25-140 expands the
toolbox for studying the impact of the ubiquitin system on immune signaling and
underscores the importance of TRAF6 E3 ligase activity in psoriasis and
rheumatoid arthritis. We propose that inhibition of TRAF6 activity by small
molecules represents a promising novel strategy for targeting autoimmune and
chronic inflammatory diseases.
PMID- 29950523
TI - The SMILE transcriptional corepressor inhibits cAMP response element-binding
protein (CREB)-mediated transactivation of gluconeogenic genes.
AB - Under fasting conditions, activation of several hepatic genes sets the stage for
gluconeogenesis in the liver. cAMP response element-binding protein (CREB), CREB
regulated transcription coactivator 2 (CRTC2), and peroxisome proliferator
activated receptor gamma coactivator 1-alpha (PGC-1alpha) are essential for this
transcriptional induction of gluconeogenic genes. PGC-1alpha induction is
mediated by activation of a CREB/CRTC2 signaling complex, and recent findings
have revealed that small heterodimer partner-interacting leucine zipper protein
(SMILE), a member of the CREB/ATF family of basic region-leucine zipper (bZIP)
transcription factors, is an insulin-inducible corepressor that decreases PGC
1alpha expression and abrogates its stimulatory effect on hepatic
gluconeogenesis. However, the molecular mechanism whereby SMILE suppresses PGC
1alpha expression is unknown. Here, we investigated SMILE's effects on the
CREB/CRTC2 signaling pathway and glucose metabolism. We found that SMILE
significantly inhibits CREB/CRTC2-induced PGC-1alpha expression by interacting
with and disrupting the CREB/CRTC2 complex. Consequently, SMILE decreased PGC
1alpha-induced hepatic gluconeogenic gene expression. Furthermore, SMILE
inhibited CREB/CRTC2-induced phosphoenolpyruvate carboxykinase (PEPCK) and
glucose-6-phosphatase (G6Pase) gene expression by directly repressing the
expression of these genes and by indirectly inhibiting the expression of PGC
1alpha via CREB/CRTC2 repression. Indeed, enhanced gluconeogenesis and
circulating blood glucose levels in mice injected with an adenovirus construct
containing a constitutively active CRTC2 variant (CRTC2-S171A) were significantly
reduced by WT SMILE, but not by leucine zipper-mutated SMILE. These results
reveal that SMILE represses CREB/CRTC2-induced PGC-1alpha expression, an insight
that may help inform potential therapeutic approaches targeting PGC-1alpha
mediated regulation of hepatic glucose metabolism.
PMID- 29950524
TI - Uncovering the molecular mechanisms behind disease-associated leptin variants.
AB - The pleiotropic hormone leptin has a pivotal role in regulating energy balance by
inhibiting hunger and increasing energy expenditure. Homozygous mutations found
in the leptin gene are associated with extreme obesity, marked hyperphagia, and
impaired immune function. Although these mutations have been characterized in
vivo, a detailed understanding of how they affect leptin structure and function
remains elusive. In the current work, we used NMR, differential scanning
calorimetry, molecular dynamics simulations, and bioinformatics calculations to
characterize the effects of these mutations on leptin structure and function and
binding to its cognate receptor. We found that mutations identified in patients
with congenital leptin deficiency not only cause leptin misfolding or
aggregation, but also cause changes in the dynamics of leptin residues on the
receptor-binding interface. Therefore, we infer that mutation-induced leptin
deficiency may arise from several distinct mechanisms including (i) blockade of
leptin receptor interface II, (ii) decreased affinity in the second step of
leptin's interaction with its receptor, (iii) leptin destabilization, and (iv)
unsuccessful threading through the covalent loop, leading to leptin
misfolding/aggregation. We propose that this expanded framework for understanding
the mechanisms underlying leptin deficiency arising from genetic mutations may be
useful in designing therapeutics for leptin-associated disorders.
PMID- 29950526
TI - The Role of Reed-Sternberg CD30 Receptor and Lymphocytes in Pathogenesis of
Disease and Its Implication for Treatment.
AB - Hodgkin lymphoma is a cancer that can be cured using standard chemotherapy with
or without radiation. Although it accounts for only 0.6% of all malignancy
worldwide, but it usually affects young adults with median age of 38 years. About
60 to 90% cases can be cured depending on its stage and 5 to 10% cases are
refractory to the first-line chemotherapy; while 20 to 30% patients experiencing
relapse after receiving the first-line chemotherapy. The relapse causes new
problem in treatment. A monoclonal antibody-chemotherapy conjugate, Brentuximab
vedotin, was approved by Food Drug Association and European Medicine since 2011
dan was approved by European Medicine Agency since 2012 to treat relapsed
classical Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). Brentuximab
vedotin has also been known as anti-CD30.CD30 or Ki-1 or TNFRSF8 is a 120-kD
glycoprotein, which is a trans-membrane receptor of Hodgkin lymphoma cells. The
glycoprotein was first identified in 1982 using monoclonal antibody against
Hodgkin lymphoma-derived cell lines. The glycoprotein was then cloned and
recognized as a member of tumor necrosis factor receptor (TNFR) superfamily,
which has intracellular, transcellular and extracellular domains. The monoclonal
antibody obviously does cause a reaction not only with the Reed-Sternberg (RS)
cells of Hodgkin lymphoma, but also with a small number of normal lymphocytes
subset, which are located at perifollicular zone as well as lymphoid tumor such
as anaplastic large cell lymphoma (ALCL) and other non-lymphoid tumor such as
embryonic and pancreas carcinoma, undifferentiated nasopharyngeal carcinoma and
malignant melanoma. Therefore, CD30 monoclonal antibody alone to confirm the
diagnosis of Hodgkin lymphoma is ineffective as it must be used together with
other panel of immunohistochemistry antibodies such as cytokeratins, carcinoma
embryonic antigen, melanoma-associated antigen and placental alkaline
phosphatide.The expression of CD30 molecules in Reed-Sternberg cells of Hodgkin
lymphoma has been demonstrated in over 98% of classical Hodgkin lymphoma cases;
however, there is a difference in staining intensity among various cases or even
in one case.
PMID- 29950525
TI - Lung cancer stage-shift following a symptom awareness campaign.
AB - BACKGROUND: Lung cancer outcomes in the UK are worse than in many other developed
nations. Symptom awareness campaigns aim to diagnose patients at an earlier stage
to improve cancer outcomes. METHODS: An early diagnosis campaign for lung cancer
commenced in Leeds, UK in 2011 comprising public and primary-care facing
components. Rates of community referral for chest X-ray and lung cancer stage
(TNM seventh edition) at presentation were collected from 2008 to 2015. Linear
trends were assessed by chi2 test for trend in proportions. Headline figures are
presented for the 3 years pre-campaign (2008-2010) and the three most recent
years for which data are available during the campaign (2013-2015). FINDINGS:
Community-ordered chest X-ray rates per year increased from 18 909 in 2008-2010
to 34 194 in 2013-2015 (80.8% increase). A significant stage shift towards
earlier stage lung cancer was seen (chi2(1)=32.2, p<0.0001). There was an 8.8
percentage point increase in the proportion of patients diagnosed with stage I/II
lung cancer (26.5% pre-campaign vs 35.3% during campaign) and a 9.3% reduction in
the absolute number of patients diagnosed with stage III/IV disease (1254 pre
campaign vs 1137 during campaign). INTERPRETATION: This is the largest described
lung cancer stage-shift in association with a symptom awareness campaign. A
causal link between the campaign and stage-shift cannot be proven but appears
plausible. Limitations of the analysis include a lack of contemporary control
population.
PMID- 29950527
TI - Cardiovascular Disease Risk Factors Among Blue and White-collar Workers in
Indonesia.
AB - BACKGROUND: cardiovascular diseases (CVD) is the most common cause of death in
Indonesia. We aimed to examine risks of CVD in workers aged 40 to 69 year related
to their occupational status. METHODS: a cross-sectional study in all provinces
of Indonesia. Data from a large-scale national health survey called RISKESDAS
were used to analyze factors associated with CVD. Analysis was restricted to the
working population aged 40 to 69 year. There were 137,378 subjects included in
the analysis. Cox's regression analysis was modified to calculate prevalence
ratio for the association of CVD with diabetes mellitus (DM), hypertension,
stress, body mass index (BMI), smoking, and particular demographic factors.
RESULTS: CVD was associated with occupation; white collar workers were about 1.6
times as likely to be diagnosed with CVD as to blue collar workers. However,
blue collar workers were more likely to report symptoms of CVD than white collar
workers. Prevalence of CVD was higher in women than men, increasing by age and
education attainment. Hypertension, DM, stress, and increased BMI added the
prediction of CVD: prevalence ratio (PR) was 1.72 (95% CI 1.59-1.86), 3.89 (95%
CI 3.43-4.44), 3.02 (95% CI 2.77-3.29) and 1.42 (95% CI 1.28-1.57) for BMI >=27
relative to <25 kg/m2, respectively. The study could not explain the association
with smoking. CONCLUSION: this study added evidence of major risk factors which
could be modified to reduce CVD. Some associations were likely to reflect access
to health care.
PMID- 29950529
TI - Diagnostic Determinants of Proliferative Lupus Nephritis Based on Clinical and
Laboratory Parameters: A Diagnostic Study.
AB - BACKGROUND: proliferative lupus nephritis (LN) has higher prevalence and worse
prognosis than non-proliferative LN. Renal biopsy plays an important role in
diagnosis and therapy of LN, but there are some obstacles in its implementation.
A diagnostic scoring system for proliferative LN is necessary, especially for
cases in which renal biopsy cannot be performed. This study aimed to develop a
diagnostic scoring system of proliferative LN based on its diagnostic
determinants including hypertension, proteinuria, hematuria, eGFR, anti-dsDNA
antibody, and C3 levels. METHODS: a cross-sectional study with total sampling
method was conducted. Our subjects were adult LN patients who underwent renal
biopsy in Cipto Mangunkusumo Hospital between January 2007 and June 2017.
RESULTS: from a total of 191 subjects with biopsy-proven LN in this study, we
found a proportion of proliferative LN of 74.8%. There were 113 subjects included
for analysis of proliferative LN determinants. The multivariate analysis
demonstrated that determinants for proliferative LN were hypertension (OR 3.39;
95% CI 1.30-8.84), eGFR <60ml/min/1.73m2 (OR 9.095; 95% CI 1.11-74.68), and low
C3 levels (OR 3.97; 95% CI 1.41-11.17). After further analysis, we found that
hypertension, eGFR <60ml/min/1.73m2, low C3 levels, and hematuria were essential
components of the diagnostic scoring system on proliferative LN. The scoring
system was tested with ROC curve and an AUC of 80.4% was obtained (95% CI 71.9
89). CONCLUSION: the proportion of proliferative LN in biopsy-proven LN patients
of Cipto Mangunkusumo Hospital is 74.8%. Components of scoring system for
proliferative LN consist of hypertension, eGFR <60ml/min/1.73m2, low C3 levels,
and hematuria.
PMID- 29950528
TI - CD30, CD15, CD50, and PAX5 Expressions as Diagnostic Markers for Hodgkin Lymphoma
(HL) and Systemic Anaplastic Large Cell Lymphoma (sALCL).
AB - BACKGROUND: the expression of CD30, CD15, CD50, and PAX5 are used to help in
confirming diagnosis of HL and sALCL; however data on the proportion of these
markers have not been available. The study was aimed to identify the proportion
of CD30, CD15, CD50 and PAX5 expressions and characteristics of patients with HL
and sALCL at Dharmais National Cancer Center Hospital between 2005 and 2015.
METHODS: a retrospective observational study was conducted using data from
medical records and histopathological results of HL and sALCL adult patients who
sought treatment at the hospital between 2005 and 2015. Immunohistochemistry
(IHC) examinations were performed and data on the proportion of positive CD30,
CD15, CD50, and PAX5 expressions were analyzed descriptively. RESULTS: a total of
45 patients were recruited in this study, with the majority (42 patients, 93.3%)
were HL patients and only 6.7% were sALCL patients. The median age of HL patients
was younger than sALCL patients; 35 (18-72 years old) versus 54 (49-61 years
old). Moreover, the immunohistochemistry examination demonstrated that the
positive CD15, CD30, CD50, and PAX5 expressions were found respectively in 37.5%,
88.9%, 31.2%, and 31.2% patients with HL; while in patients with sALCL, in spite
of their small sample size, positive CD30, CD15, CD50 and PAX5 expressions were
found in 100%; 66,7%; 50%; and 50%, respectively. Overall, CD15, CD50, and PAX5
positive expressions were found in 39.5%, 32.4%, and 32.4% patients who had HL
and sALCL; while positive expression of CD30 was found in 89.5% of them.
CONCLUSION: present study shows that almost 90% patients have positive CD30
expression; while the positive expressions of CD15, CD50, and PAX5 are found in
less than 40% patients. It indicates that CD30 is an important diagnostic marker
for HL and sALCL and it may improve treatment strategy.
PMID- 29950530
TI - 7 Years Experience of Living Donor Kidney Transplantation in Indonesia: A
Retrospective Cohort Study.
AB - BACKGROUND: kidney transplantation has been developing rapidly in Indonesia in
recent years, yet data on transplants' characteristics and survival is still
unavailable. In Indonesia, only living donors are permitted. Living donor are
advantageous, but challenging to recruit. This study aimed to establish the graft
and patient survival rates and to describe the characteristics of recipient and
donor as well as the process of donor recruitment and evaluation of kidney
transplantation in Indonesia. METHODS: the study was a retrospective cohort on
all donors and kidney transplant recipients at Cipto Mangunkusumo General
Hospital (CMGH) from January 2011 to May 2017. Only recipients from January 2011
to May 2014 were included to establish the 1-year and 3-year graft and patient
survival; which were described using Kaplan-Meier method. RESULTS: data from 492
kidney transplant procedures were obtained (donor median age, 30 (17 - 66) years;
25.1% were family-related. Recipients mean age, 47 (SD 13.18 years). Data from
total of 138 kidney transplant recipients were further analyzed. The 1-year death
censored graft survival, all-cause graft survival and patient survival were 92
%, 82.6 % and 87%. The 3-year death-censored graft survival, all-cause graft
survival and patient survival were 90.6%, 76.1% and 79.7%. Kaplan-Meier's curve
showed the highest mortality rates occured in the early months. CONCLUSION: the 1
year graft and patient survival rate were 92% and 87%. The 3-year graft and
patient survival rate were 90.6% and 79.7%. Only small percentage of donor were
family-related. Living donor recruitment and evaluation are still a big challenge
in Indonesia.
PMID- 29950531
TI - Comparison of Specific Immunoglobulin E with the Skin Prick Test in the Diagnosis
of House Dust Mites and Cockroach Sensitization in Patients with Asthma and/or
Allergic Rhinitis.
AB - BACKGROUND: nowadays, specific IgE measurement has been conducted in Indonesia,
however there is still lack of data regarding diagnostic test to detect inhalant
allergen in patients with respiratory allergies.This study aimed to determine the
accuracy of specific IgE test in diagnosing specific sensitization of inhalant
allergen in patients with respiratory allergies. METHODS: this was a cross
sectional study in patients with respiratory allergies and part of epidemiology
study regarding to specific IgE sensitization in Allergy-Immunollogy Division,
Cipto Mangunkusumo Hospital, Jakarta within November-December 2016. Measurement
of specific IgE sensitization using Immunoblot method (Euroline(r), Euroimmun AG,
Germany). The tested allergen is house dust mites [Dermatophagoides pteronyssinus
(Der p), Dermatophagoides farinae (Der f), Blomia tropicalis (Blo t)] and
cockroach [Blatella germanica (Bla g)]. The result is compared with gold
standard, skin prick test. The diagnostic result includes sensitivity,
specificity, positive predictive value (PPV), negative predictive value (NPV),
positive likelihood ratio (LR+), and negative likelihood ratio (LR-). RESULTS: a
total of 101 patients were enrolled; 77 (76.2%) were women. Patients mean age was
38.8 years old. Based on SPT, sensitization was highest for Blo t (76.2%),
followed by Der p (70.3%), Der f (69.3%), and Bla g (41.6%). Specific IgE
sensitization was highest for Der f (52.9%), followed by Der p (38.2%), Blo t
(33.3%) and Bla g (10.8%). Der p allergen had 50.7% sentivity, 90% specificity,
92.3% PPV, 43.5% NPV, 5.1 LR+ and 0.1LR-. Der f showed 71.4% sensitivity, 87.1%
specificity, 82.6% PPV, 57.4% NPV, 5.5 LR+ and 0.3 LR-. Blo t allergen had 41.6%
sensitivity, 91.7% specificity, 94.1% PPV, 32.8% NPV, 5.0 LR+, and 0.6 LR-. Bla g
allergen had 23.8% sensitivity, 98.3% specificity, 90.9% PPV, 64.4% NPV, 14.5 LR+
and 0.8 LR-. CONCLUSION: serum specific IgE testing to common inhalant allergen
in patients with respiratory allergy showed only low-to-moderate sensitivity, but
high specificity and PPV. This new assay can be used to diagnose allergen
sensitization in the population with high prevalence of TDR and cockroach.
PMID- 29950532
TI - Correlation Between Vitreous Advanced Glycation End Products, and D-dimer with
Blood HbA1c Levels in Proliferative Diabetic Retinopathy.
AB - BACKGROUND: proliferative diabetic retinopathy (DR) is an advanced form of DR
that eventually could lead to blindness. Levels of vitreous advanced glycation
end products (AGEs) and D-dimer may reflect the pathological changes in the
retina, but only few studies have assessed their correlation with blood
hemoglobin A1C (HbA1c) levels. This study aimed to find the association between
blood HbA1c levels with vitreous AGEs and D-dimer levels in patients with
proliferative DR. METHODS: an analytical cross-sectional study was performed in
subjects with proliferative DR who underwent vitrectomy. Subjects were divided
into 2 subgroups, i.e. uncontrolled (HbA1c >7%) and controlled (HbA1c <7%)
groups. Vitreous AGEs and D-dimer levels were assessed; the levels were compared
between uncontrolled and controlled hyperglycemic patients. Statistic correlation
tests were also performed for evaluating blood HbA1c, vitreous AGEs, and D-dimer
levels. RESULTS: a total of 47 patients were enrolled in this study and 32
(68.1%) of them were women. Median vitreous AGEs level was 11.0 (3.0 - 48.0)
ug/mL; whereas median vitreous D-dimers level was 5,446.0 (44.0 - 37,394.0 )
ng/mL. The median vitreous AGEs levels was significantly higher in patients with
uncontrolled vs. controlled hyperglycemia (14.0 vs. 4.0 mg/mL; p<0.001). There
was a significant positive correlation with moderate strength between blood HbA1c
level and vitreous AGEs level (r=0.524; r2=0.130; p=0.0001). Blood HbA1c level
could be used to predict vitreous AGEs level by using the following calculation:
vitreous AGEs = -1.442+ (1.740xblood HbA1c). Vitreous D-dimer levels were not
significantly different between uncontrolled and controlled hyperglycemia (median
4607.5 vs. 5701.6 ng/mL; p = 0.458). There was a positive significant correlation
between blood HbA1c and vitreous D-dimer levels (r = 0.342; p = 0.019); however
the correlation was weak. Vitreous AGEs level had a positive significant
correlation with vitreous D-dimer levels (r = 0.292; p = 0.046) and the
correlation strength was also weak. CONCLUSION: median vitreous AGEs levels were
significantly higher in proliferative DR patients with uncontrolled than those
with controlled hyperglycemia. Blood HbA1c level can be used to assess vitreous
AGEs level in patients with proliferative DR by using the following calculation:
vitreous AGEs = -1.442+(1.740 x HbA1c). However, the blood HbA1c level can not be
used to predict vitreous D-dimer level in patients with proliferative DR.
PMID- 29950533
TI - The Benefit of Interferon-Gamma Release Assay for Diagnosis of Extrapulmonary
Tuberculosis.
AB - BACKGROUND: there are many researches about IGRA in extrapulmonary Tuberculosis
(TB), but there only few data from developing countries. This was the first
research about the utility of IGRA in extrapulmonary TB performed in Indonesia as
developing country with the 2nd most frequent of TB cases in the world. This
study aimed to identify the advantage of IGRA examination in diagnosing
extrapulmonary TB. METHODS: eighty-four patients, presumed to have extrapulmonary
TB were examined with IGRA and gold standard examination. The gold standard
examination was performed by histopathologic examination, and tissue smear for
acid-fast bacilli. RESULTS: among 84 patients included in the study, 57 patients
were tested positive with gold standard, where 50 patients among them were also
tested positive with IGRA. Among 27 patients tested negative with gold standard,
IGRA positive was found in 10 patients. Lymphadenitis was the most common
manifestation of the extrapulmonary TB. Diagnostic test from IGRA for
extrapulmonary TB found as follows: sensitivity 87,71%, specificity 63%, positive
predictive value 83,33%, and negative predictive value 70,83%. CONCLUSION: IGRA
could be used as supporting tool in the diagnosis of extrapulmonary TB. The
negative result, however, does not indicate absence of TB infection.
PMID- 29950534
TI - The Coexistence of Systemic Lupus Erythematosus and Psoriasis: Is It Possible?
AB - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with various
clinical disorders and frequent exacerbations. Psoriasis vulgaris is a common
skin disorder which affect 1-3% of general populations. The pathophysiology
regarding the coexistence of these diseases is not fully understood. Therapeutic
challenges arise since the treatment one of these diseases may aggravate the
other. We reported two cases of SLE with psoriasis vulgaris with clinical
manifestations as recurrent erythroderma with photosensitivity. Improvement in
clinical condition was observed after treating the patients with
methylprednisolone combined with methotrexate. The coexistence SLE and psoriasis
are considered very rare. The presence of this overlap syndrome may precede one
another or occur simultaneously and is closely related with the presence of anti
Ro/SSA. Thus, it raises new challenge regarding its relationships, diagnosis,
therapeutic, and management.
PMID- 29950535
TI - A Chronic Lymphocytic Leukemia Patient with Progressive Multifocal
Leukoencephalopathy Caused by John Cunningham Virus.
AB - Progressive multifocal leukoencephalopathy (PML) is a rare but fatal disease
leading to severe neurological impairments. PML is a clinical manifestation,
which is usually associated with John Cunningham virus (JCV) infection. It is
also correlated to malignancies that mainly include hematologic malignancies such
as chronic lymphocytic leukemia (CLL). Until now, no specific treatment has been
established for JCV-induced PML; therefore, the prognosis of this disease is
poor.We present a case of a 67-year-old woman who suffered from CLL with a chief
complaint of seizure. Her clinical symptoms, results of brain MRI and biopsy were
suggestive for the JCV-induced PML. The patient had received treatment using
mefloquine at dose of 250 mg/day with no clinical improvement.
PMID- 29950536
TI - Obesity as the Sequel of Childhood Stunting: Ghrelin and GHSR Gene Polymorphism
Explained.
AB - Stunting or short stature in children is a significant nutritional problem in
developing and underdeveloped countries. Stunting during childhood might affect
brain development and impair development cognitive function. Additionally, this
condition associated with the increased risk for obesity during adulthood.
Several studies have shown that the increment risk of obesity and overweight in
children with a short stature was due to their metabolic efficiency. Children
with stunting have lower resting energy expenditure compared to non stunting
children. Additionally, stunted children has higher respiratory quotient and
carbohydrate oxidation but lower fat oxidation compared to non-stunting children.
These results might explain why stunted children easily become obese, which is
due to lower fat oxidation and leading to tendency to store fat.This review
discussed the current status on studies in the nutrigenetic aspects of the
relationship between stunting in the childhood and obesity in adulthood. I
hypothesized that stunted children are more likely to become obese in their later
life because they have lower metabolic rate and higher tendency of fat storage.
There are several candidate genes and pathway involved in obesity and I suspected
that ghrelin and its receptor growth hormone secretague receptor (GHSR) were
responsible.
PMID- 29950537
TI - Double Culprits in a Patient with ST Elevation Myocardial Infarction: A
Challenging But Rewarding Case.
AB - Myocardial infarction simultaneously involving two or more culprit lesions is
extremely rare and usually has a poor clinical outcomes including mortality.
Management of this complicated condition is challenging and limited time.
Nevertheless, autopsy studies revealed that thrombotic occlusion of more than one
major epicardium coronary artery is not uncommon. A 68-year-old woman presented
with sudden onset of limited breath and chest discomfort since two hours prior to
admission. She also felt exert dyspnoea since one month ago. She has two risk
factors that were uncontrolled that is hypertension (HT) and type 2 diabetes
mellitus (DM). On admission, she succumbed into cardiogenic shock and pulmonary
oedema. ECG revealed a diminished R wave in V2-V4 with ST elevation in V2-V5 and
in aVR. Biphasic T wave was seen in V2-V6. The working diagnosis was anterior
STEMI, Killip class IV with thrombolysis in Myocardial Infarction (TIMI) score of
8. While being transferred to catheter lab, she gasped, became desaturation, and
was intubated prior to procedure. The patient was given double inotropes which
run maximally. By Coronary angiography, there were occlusions at the LAD and LCX.
Stent was applied at proximal LAD and LCX. Subsequently, patient's condition
improved and post-procedure ECG showed improvement in aVR and precordial leads,
and ST elevation was significantly diminished from V5 and aVR, and R wave came
back in V2-V4.Previous study found around 50% of STEMI patients had multi-vessels
diseases. In this case, ECG suggested LAD region infarction with ST elevation in
aVR, commonly associated with left main stenosis (LMS) involvement.Thrombus
aspiration in LAD and LCX yielded hemodynamic improvement. V-stenting technique,
introduced in 1996, allows delivery and implantation of 2 stents together, and
therefore shorten the stent deployment time.
PMID- 29950538
TI - Comparison of Deferiprone to Deferasirox and Deferoxamine to Cardiac and Hepatic
T2* MRI in Thalassemia Patients: Evidence-based Case Report.
AB - BACKGROUND: there are currently three iron chelator readily available for
patients Indonesia; deferiprone/DFP (branded as Ferriprox), deferasirox/DFX
(branded as Exjade) and deferoxamine/DFO (branded as Desferal). This study aims
to determine which iron chelator is the most efficient in reducing cardiac and
hepatic iron overload (measured by means of T2* MRI). METHODS: journal search
with determined MeSH term was done in PubMed and Scopus. Studies that looked upon
thalassemia major patient in all ages with usage of monotherapy iron chelation
and its effect on myocardial T2* MRI and/or liver T2* MRI was included. Appraisal
of studies was done using Oxford's CEBM appraisal tools and Joanna Brigs
Institute critical appraisal tools. RESULTS: total of 11 studies with grand total
of 611 samples were included. Mean T2* MRI value or (when available) mean changes
in T2* MRI value after usage of specific iron chelator was gained from all the
studies included. Comparison study and individual studies shows better control
and increase of myocardial T2* MRI in those with DFP, and of liver T2* in those
with good adherence to DFO chelation. CONCLUSION: DFP is superior in controlling
or reducing myocardial iron load (as proven by mT2* MRI) and DFO had better
capabilities in controlling or reducing hepatic iron load (as proven by liver T2*
MRI). Studies with longer observation and larger samples is needed to see a
significant changes of T2* MRI in DFX.
PMID- 29950539
TI - Current Diagnosis and Management of Graves' Disease.
AB - Graves' disease is an autoimmune disorder which affect thyroid gland. Graves'
disease is the most common cause of hyperthyroidism and thyrotoxicosis.
Understanding of disease pathophysiology, diagnostic and treatment strategies,
and prevention of disease relapse are important for all clinicians especially
internal medicine specialist to give optimal and comprehensive management for
Graves' disease patients. This article highlights clinical points to treat
Grave's disease patients from reviews and latest guidelines from American Thyroid
Association (ATA), European Thyroid Association (ETA), and Japan Thyroid
Association/ Japan Endocrine Society.
PMID- 29950540
TI - [Body weight and bone/calcium metabolism. Body mass index, bone mineral density,
and fracture.]
AB - High body weight and high BMI has long been thought to protect against
osteoporosis and fragility fractures. However, recent studies indicate that obese
individuals fracture risk in some body sites increased with obesity, although it
is consistent that obesity remains a protective factor for hip fracture. The
association between BMI and fracture risk is complex, differs among fracture
sites, and is modified by BMD. FRAX(r) tool including weight and height is
effective to predict fracture even among obesity persons.
PMID- 29950541
TI - [Body weight and bone/calcium metabolism. Bone and calcium metabolism in
metabolic syndrome.]
AB - Accumulating studies have shown that metabolic syndrome is involved in the
disturbance of bone and calcium metablism. Main pathophysiological conditions,
such as visceral fat obesity and insulin resistance, may cause abnormal bone
metabolism and bone quality deterioration. Moreover, recent studies have reported
that components of metabolic syndrome, such as diabetes mellitus, dyslipidemia,
and hypertension, are associated with increased fracture risk. Therefore, we
should consider the posibility that patients with metabolic syndrome have bone
quality deterioration even if they have normal bone mineral density, and evaluate
their fracture risk in clinical settings.
PMID- 29950542
TI - [Body weight and bone/calcium metabolism. Sarcopenia and its relationship with
bone and calcium metabolism.]
AB - Sarcopenia is characterized by age-related loss of skeletal muscle mass, strength
and function, and its diagnostic criteria as well as the practical guideline have
been established. Although underlying mechanisms of sarcopenia remains to be
fully elucidated, recent progress in research has suggested the concept of muscle
bone connection including the association between sarcopenia and osteoporosis.
PMID- 29950543
TI - [Body weight and bone/calcium metabolism. Role of adipokine in bone metabolism.]
AB - Since leptin was discovered in 1994, we considered the adipose tissue was not a
"stockroom" with energy and being the endocrine-organ which secretes a various
hormone, as called adipokine, which has various physiological activity. Much
research was done about the effect of adipokine to each organ and disease concept
of metabolic syndrome was established that induces metabolic disorders and
atherosclerotic diseases by dysregulation of adipokine following visceral fat
accumulation. Also, role of adipokine in bone metabolism becomes clear gradually.
In this review, former knowledge is outlined mainly about leptin and adiponectin.
PMID- 29950544
TI - [Body weight and bone/calcium metabolism. Muscle, myokines and bone/calcium
metabolism.]
AB - The interactions between skeletal muscle and bone have been noted, and muscle
influences bone metabolism by secreting myokines. Myostatin is known as a
myostatic factor through an inhibition of Smad2/3 signaling in muscle. It is
involved in the pathophysiology of rheumatoid arthritis via a stimulation of bone
resorption. Follistatin might be involved in the regulation of muscle and bone by
gravity change through an attenuation of myostatin action. Irisin with energy
metabolism improvement actions is related to the effects of mechanical stress or
exercise on muscle and bone. The research of myokines might lead to the
improvement of clinical practice of sarcopenia and osteoporosis.
PMID- 29950545
TI - [Body weight and bone/calcium metabolism. Relationship between insulin/glucose
metabolism and bone/calcium metabolism.]
AB - Recent advances demonstrated that osteoporosis is one of the major complications
in diabetes. In Diabetic conditions, both bone material properties and bone
microarchitecture are impaired, resulting in the decline in bone strength.
Furthermore, bone-derived osteocalcin stimulates insulin secretion, thereby
regulates the whole body glucose metabolism. Thus, it was revealed that bone
metabolism and glucose metabolism are intimately involved.
PMID- 29950546
TI - [Body weight and bone/calcium metabolism. The effect of incretin hormones on bone
and calcium metabolism.]
AB - Incretins are gastro-intestinal hormones released from enteroendocrine cells in
response to food intake. Incretins such as glucose-dependent insulinotropic
peptide(GIP)and glucagon-like peptide 1(GLP-1)modulate glucose homeostasis by
regulating glucose-dependent insulin release from pancreatic betacells.
Dipeptidyl peptidase-4(DPP-4)inhibitors and GLP-1 receptor agonists are incretin
based drugs that have been used for the management of hyperglycemia and obesity
in patients with type 2 diabetes mellitus. Although experimental studies have
shown that incretin improves bone quality and increases bone mass in rodents,
further studies are necessary to clarify the effect of incretin-based drugs on
bone mineral density and risk of fractures in humans.
PMID- 29950547
TI - [Body weight and bone/calcium metabolism. FSH and obesity, osteoporosis.]
AB - It is well known that the rise of FSH is a hallmark of menopause associated with
osteoporosis and visceral adiposity. Recent days, Zahidi's group reported that
blocking FSH signals prevents bone loss in ovariectomized mice by inhibiting bone
resorption and stimulating bone synthesis. The same research group also showed
that blocking FSH action reduces body fat volume by promoting beige fat
thermogenesis. These findings open new doors for novel and complementary
treatments addressing post-menopausal osteoporosis and metabolic diseases.
PMID- 29950548
TI - [Body weight and bone/calcium metabolism. Obesity and vitamin D.]
AB - Obesity is associated with lower serum 25(OH)D level via several mechanisms
including sequestration of fat soluble vitamin D in increased fat mass. Since
obesity is the major cause of insulin resistance and type 2 diabetes, lower serum
25(OH)D level is also associated with these conditions. Non-surgical weight
reduction, especially that results in decreased visceral fat mass, is associated
with an improvement in insulin resistance and a small but significant increase in
serum 25(OH)D level. Whether the latter is independently associated with the
former is not known. Plural meta-analyses reported that vitamin D supplementation
per se without life-style intervention is not associated with a significant
weight reduction. However, recent meta-analyses of randomized controlled trials
in which large doses vitamin D over 2,000 IU/day supplemented to type 2 diabetes
patients revealed a small but significant improvement in indices of insulin
resistance and glycemic control. The beneficial effects of vitamin D
supplementation on glucose metabolism appeared to be more prominent in non-obese
subjects in whom higher serum 25(OH)D level were attained, suggesting potential
benefits of vitamin D on glucose metabolism is not mediated by weight or fat mass
control.
PMID- 29950549
TI - [Body weight and bone/calcium metabolism. Treatment of osteoporosis with
diabetes.]
AB - Nutritional guidance and exercise should be beneficial as well as pharmacotherapy
in life style-related diseases including diabetes and osteoporosis. Sufficient
and appropriate energy intake with protein, calcium and vitamin D is good for
bone and muscles in osteoporotic patient. Diabetes patients are often recommended
to reduce body weight. However, losing weight could be related to bone loss.
Therefore, we should pay attention to keep balance between glucose metabolism and
bone metabolism in the patients with both diseases. As for pharmacotherapy in
osteoporosis with diabetes, there is so far no specific recommendation. Fall risk
assessment and guidance should be emphasized in diabetes patient with
osteoporosis, because they could have more fall risk due to diabetic
complications such as neuropathy and retinopathy.
PMID- 29950550
TI - [Body weight and bone/calcium metabolism. Glucose-lowering agents and fracture
risk.]
AB - Diabetes is associated with increased fracture risk, involving a variety of
factors. Besides poor glycemic control itself, some glucose-lowering agents are
also associated with increased fracture risk. Thiazolidinediones increase
fracture risk probably through inhibition of bone formation as well as increased
resorption leading to decreased BMD. Sodium-glucose cotransporter(SGLT)-2
inhibitors have been reported to decrease BMD and increase fracture risk.
However, the class effect of SGLT-2 inhibitors on bone metabolism remains to be
established. In diabetic patients, especially in those with high fracture risk
such as postmenopausal women, careful selection of glucose-lowering agents as
well as appropriate and timely intervention for osteoporosis is necessary.
PMID- 29950551
TI - [Body weight and bone/calcium metabolism. Response of bone metabolism after
bariatric surgery.]
AB - While bariatric surgery is an effective treatment for severe obesity, these
procedures may have unfavorable effects on bone and mineral metabolism. The most
pronounced abnormalities are disorders of calcium/vitamin D metabolism, bone
loss, as well as increased risk of bone fracture. These changes that occur after
surgery vary by procedure type. Proposed mechanisms include skeletal unloading,
malabsorption, secondary hyperparathyroidism and changes in gut hormones. This
review explores bone response to bariatric surgery, potential mechanisms for
these changes.
PMID- 29950552
TI - [Body weight and bone/calcium metabolism. Bone and calcium metabolism in anorexia
nervosa.]
AB - Osteoporosis is one of chief complications of anorexia nervosa. Their calcium
intake decreases and 84%are lack of vitamin D. The abnormal bone metabolism in
severely emaciated patients with anorexia nervosa involves both a reduction in
bone formation and an increase in bone resorption. The annual change in lumbar
bone mineral density(BMD)is significantly correlated with body mass index(BMI)at
the entry. The critical BMI for a positive increase in BMD was 16.4+/-0.3 kg/m2.
Since 30%of patients are lack of vitamin K, their bone quality deteriorates. The
risk factors of a decrease in lumbar vertebrae BMD is a duration of emaciation
when both serum levels of insulin-like growth factor-I as a potent osteogenic
factor and estradiol as a powerful bone resorption inhibitor decrease. Therefore,
the prevention and the treatment are weight gain. However, the patient does not
accept weight gain easily. Active form vitamin D3 of 0.5MUg/day or 30-45 mg/day
of vitamin K2 preparation prevents the further decrease in bone mineral density.
Eldecalcitol of 0.5MUg/day shows about 5%increase in lumbar vertebrae BMD in
first year. Bisphosphonate and a RANK ligand inhibitors, denosumab should not be
used for young patients and women in hope of the pregnancy.
PMID- 29950553
TI - [Taste receptors in multiple organs.]
AB - There are five basic taste qualities, umami, sweet, bitter, salty and sour
tastes. These taste qualities are transduced through corresponding taste
receptors that reside on taste cells in the oral cavity. Unlike salty or sour
receptors, receptors for umami, sweet and bitter belong to G protein coupled
receptor family. Recently, it has become apparent that taste receptors are
localized in various cells and tissues other than those in the oral cavity, which
similarly function for taste transduction. In this review, we will discuss
expression and function of these taste receptors based on knowledge accumulated.
PMID- 29950554
TI - Clinical factors affecting progression-free survival with crizotinib in ALK
positive non-small cell lung cancer.
AB - Background/Aims: Although crizotinib is standard chemotherapy for advanced
anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC),
clinical factors affecting progression-free survival (PFS) have not been
reported. The purpose of this study was to identify clinical factors affecting
PFS of crizotinib and develop a prognostic model for advanced ALK-positive NSCLC.
Methods: Clinicopathologic features of patients enrolled in PROFILE 1001, 1005,
1007, and 1014 (training cohort) were reviewed. We conducted multivariate Cox
analysis for PFS and overall survival (OS) in the training cohort (n = 159) and
generated a proportional hazards model based on significant clinicopathologic
factors, and then validated the model in an independent validation cohort (n =
40). Results: In the training cohort, the objective response rate was 81.5%.
Median PFS and OS from the start of crizotinib were 12.4 and 31.3 months,
respectively. Multivariate Cox analysis showed poor performance status, number of
metastatic organs (>= 3), and no response to crizotinib independently associated
shorter PFS. Based on a score derived from these three factors, median PFS and OS
of patients with one or two factors were significantly shorter compared to those
without these factors (median PFS, 22.4 months vs. 10.5 months vs. 6.5 months;
median OS, not reached vs. 29.1 months vs. 11.8 months, respectively; p < 0.001
for each group). This model also had validated in an independent validation
cohort. Conclusions: Performance status, number of metastatic organs, and
response to crizotinib affected PFS of crizotinib in ALK-positive NSCLC. Based on
these factors, we developed a simple and useful prediction model for PFS.
PMID- 29950555
TI - Comparison of Load-Bearing Capacities of 3-Unit Fiber-Reinforced Composite
Adhesive Bridges with Different Framework Designs.
AB - BACKGROUND The aim of this study was to investigate and compare the load-bearing
capacities of three-unit direct resin-bonded fiber-reinforced composite fixed
dental prosthesis with different framework designs. MATERIAL AND METHODS Sixty
mandibular premolar and molar teeth without caries were collected and direct
glass fiber-resin fixed FDPs were divided into 6 groups (n=10). Each group was
restored via direct technique with different designs. In Group 1, the inlay
retained bridges formed 2 unidirectional FRC frameworks and pontic-reinforced
transversal FRC. In Group 2, the inlay-retained bridges were supported by
unidirectional lingual and occlusal FRC frameworks. Group 3, had buccal and
lingual unidirectional FRC frameworks without the inlay cavities. Group 4 had
reinforced inlay cavities and buccal-lingual FRC with unidirectional FRC
frameworks. Group 5, had a circular form of fiber reinforcement around cusps in
addition to buccal-lingual FRC frameworks. Group 6 had a circular form of fiber
reinforcement around cusps with 2 bidirectional FRC frameworks into inlay
cavities. All groups were loaded until final fracture using a universal testing
machine at a crosshead speed of 1 mm/min. RESULTS Mean values of the groups were
determined with ANOVA and Tukey HSD. When all data were evaluated, Group 6 had
the highest load-bearing capacities and revealed significant differences from
Group 3 and Group 4. Group 6 had the highest strain (p>0.05). When the fracture
patterns were investigated, Group 6 had the durability to sustain fracture
propagation within the restoration. CONCLUSIONS The efficiency of fiber
reinforcement of the restorations alters not only the amount of fiber, but also
the design of the restoration with fibers.
PMID- 29950556
TI - Invasive Thyroglossal Duct Cyst Papillary Carcinoma: A Case Report and Review of
the Literature.
AB - BACKGROUND Thyroglossal duct cyst is a common congenital anomaly of the thyroid
gland, usually found centrally. The presence of malignancy occurring in a
thyroglossal duct cyst is a rare condition, accounting only for 1% of all cases
of thyroglossal duct cyst. This report is of a rare case of papillary carcinoma
arising in a thyroglossal duct cyst and includes a review of the literature. CASE
REPORT A 27-year-old female patient was referred to our department with a
painless cystic mass in the neck. After initial physical examination and
endocrinology investigations, a fine needle aspiration (FNA) of the cyst was
performed. Cytology showed a papillary neoplasm. The patient underwent total
thyroidectomy and surgical excision of the thyroglossal duct cyst (the Sistrunk's
procedure). Histopathology of the surgical excision specimen showed a
thyroglossal duct cyst with a maximum diameter of 7.5 cm containing a primary
invasive papillary carcinoma, measuring 1.5 cm in diameter that infiltrated into
the cyst wall. The remaining thyroid gland was normal. CONCLUSIONS Thyroglossal
duct carcinoma, most commonly papillary carcinoma, is a rare condition that
should be considered in patients presenting with cystic midline neck masses.
Surgery and complete excision is the main treatment and the optimal patient
management includes multidisciplinary consultation in order to improve survival.
The diagnosis of malignancy is made postoperatively, as in the present case.
PMID- 29950557
TI - GABA promotes survival and axonal regeneration in identifiable descending neurons
after spinal cord injury in larval lampreys.
AB - The poor regenerative capacity of descending neurons is one of the main causes of
the lack of recovery after spinal cord injury (SCI). Thus, it is of crucial
importance to find ways to promote axonal regeneration. In addition, the
prevention of retrograde degeneration leading to the atrophy/death of descending
neurons is an obvious prerequisite to activate axonal regeneration. Lampreys show
an amazing regenerative capacity after SCI. Recent histological work in lampreys
suggested that GABA, which is massively released after a SCI, could promote the
survival of descending neurons. Here, we aimed to study if GABA, acting through
GABAB receptors, promotes the survival and axonal regeneration of descending
neurons of larval sea lampreys after a complete SCI. First, we used in situ
hybridization to confirm that identifiable descending neurons of late-stage
larvae express the gabab1 subunit of the GABAB receptor. We also observed an
acute increase in the expression of this subunit in descending neurons after SCI,
which further supported the possible role of GABA and GABAB receptors in
promoting the survival and regeneration of these neurons. So, we performed gain
and loss of function experiments to confirm this hypothesis. Treatments with GABA
and baclofen (GABAB agonist) significantly reduced caspase activation in
descending neurons 2 weeks after a complete SCI. Long-term treatments with GABOB
(a GABA analogue) and baclofen significantly promoted axonal regeneration of
descending neurons after SCI. These data indicate that GABAergic signalling
through GABAB receptors promotes the survival and regeneration of descending
neurons after SCI. Finally, we used morpholinos against the gabab1 subunit to
knockdown the expression of the GABAB receptor in descending neurons. Long-term
morpholino treatments caused a significant inhibition of axonal regeneration.
This shows that endogenous GABA promotes axonal regeneration after a complete SCI
in lampreys by activating GABAB receptors.
PMID- 29950558
TI - Synthetic CRISPR-Cas gene activators for transcriptional reprogramming in
bacteria.
AB - Methods to regulate gene expression programs in bacterial cells are limited by
the absence of effective gene activators. To address this challenge, we have
developed synthetic bacterial transcriptional activators in E. coli by linking
activation domains to programmable CRISPR-Cas DNA binding domains. Effective gene
activation requires target sites situated in a narrow region just upstream of the
transcription start site, in sharp contrast to the relatively flexible target
site requirements for gene activation in eukaryotic cells. Together with existing
tools for CRISPRi gene repression, these bacterial activators enable programmable
control over multiple genes with simultaneous activation and repression. Further,
the entire gene expression program can be switched on by inducing expression of
the CRISPR-Cas system. This work will provide a foundation for engineering
synthetic bacterial cellular devices with applications including diagnostics,
therapeutics, and industrial biosynthesis.
PMID- 29950560
TI - KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa
cell tumors of the ovary.
AB - Adult-type granulosa cell tumors of the ovary (aGCTs) are rare gynecologic
malignancies that exhibit a high frequency of somatic FOXL2 c.C402G (p.Cys134Trp)
mutation. Treatment of relapsed aGCT remains a significant clinical challenge.
Here we show, using whole-exome and cancer gene panel sequencing of 79 aGCTs from
two independent cohorts, that truncating mutation of the histone lysine
methyltransferase gene KMT2D (also known as MLL2) is a recurrent somatic event in
aGCT. Mono-allelic KMT2D-truncating mutations are more frequent in recurrent
(10/44, 23%) compared with primary (1/35, 3%) aGCTs (p = 0.02, two-sided Fisher's
exact test). IHC detects additional non-KMT2D-mutated aGCTs with loss of nuclear
KMT2D expression, suggesting that non-genetic KMT2D inactivation may occur in
this tumor type. These findings identify KMT2D inactivation as a novel driver
event in aGCTs and suggest that mutation of this gene may increase the risk of
disease recurrence.
PMID- 29950559
TI - Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF
targeted therapy.
AB - Whereas significant anti-tumor responses are observed in most BRAFV600E-mutant
melanoma patients exposed to MAPK-targeting agents, resistance almost invariably
develops. Here, we show that in therapy-responsive cells BRAF inhibition induces
downregulation of the processing of Sterol Regulator Element Binding (SREBP-1)
and thereby lipogenesis. Irrespective of the escape mechanism, therapy-resistant
cells invariably restore this process to promote lipid saturation and protect
melanoma from ROS-induced damage and lipid peroxidation. Importantly,
pharmacological SREBP-1 inhibition sensitizes BRAFV600E-mutant therapy-resistant
melanoma to BRAFV600E inhibitors both in vitro and in a pre-clinical PDX in vivo
model. Together, these data indicate that targeting SREBP-1-induced lipogenesis
may offer a new avenue to overcome acquisition of resistance to BRAF-targeted
therapy. This work also provides evidence that targeting vulnerabilities
downstream of oncogenic signaling offers new possibilities in overcoming
resistance to targeted therapies.
PMID- 29950562
TI - A dopaminergic switch for fear to safety transitions.
AB - Overcoming aversive emotional memories requires neural systems that detect when
fear responses are no longer appropriate so that they can be extinguished. The
midbrain ventral tegmental area (VTA) dopamine system has been implicated in
reward and more broadly in signaling when a better-than-expected outcome has
occurred. This suggests that it may be important in guiding fear to safety
transitions. We report that when an expected aversive outcome does not occur,
activity in midbrain dopamine neurons is necessary to extinguish behavioral fear
responses and engage molecular signaling events in extinction learning circuits.
Furthermore, a specific dopamine projection to the nucleus accumbens medial shell
is partially responsible for this effect. In contrast, a separate dopamine
projection to the medial prefrontal cortex opposes extinction learning. This
demonstrates a novel function for the canonical VTA-dopamine reward system and
reveals opposing behavioral roles for different dopamine neuron projections in
fear extinction learning.
PMID- 29950563
TI - Characterizing human subchondral bone properties using near-infrared (NIR)
spectroscopy.
AB - Degenerative joint conditions are often characterized by changes in articular
cartilage and subchondral bone properties. These changes are often associated
with subchondral plate thickness and trabecular bone morphology. Thus, evaluating
subchondral bone integrity could provide essential insights for diagnosis of
joint pathologies. This study investigates the potential of optical spectroscopy
for characterizing human subchondral bone properties. Osteochondral samples (n =
50) were extracted from human cadaver knees (n = 13) at four anatomical locations
and subjected to NIR spectroscopy. The samples were then imaged using micro
computed tomography to determine subchondral bone morphometric properties,
including: plate thickness (Sb.Th), trabecular thickness (Tb.Th), volume fraction
(BV/TV), and structure model index (SMI). The relationship between the
subchondral bone properties and spectral data in the 1st (650-950 nm), 2nd (1100
1350 nm) and 3rd (1600-1870 nm) optical windows were investigated using partial
least squares (PLS) regression multivariate technique. Significant correlations
(p < 0.0001) and relatively low prediction errors were obtained between spectral
data in the 1st optical window and Sb.Th (R2 = 92.3%, error = 7.1%), Tb.Th (R2 =
88.4%, error = 6.7%), BV/TV (R2 = 83%, error = 9.8%) and SMI (R2 = 79.7%, error =
10.8%). Thus, NIR spectroscopy in the 1st tissue optical window is capable of
characterizing and estimating subchondral bone properties, and can potentially be
adapted during arthroscopy.
PMID- 29950561
TI - Nuclear Smad6 promotes gliomagenesis by negatively regulating PIAS3-mediated
STAT3 inhibition.
AB - To date, the molecular mechanism underlying constitutive signal transducer and
activator of transcription 3 (STAT3) activation in gliomas is largely unclear. In
this study, we report that Smad6 is overexpressed in nuclei of glioma cells,
which correlates with poor patient survival and regulates STAT3 activity via
negatively regulating the Protein Inhibitors of Activated STAT3 (PIAS3).
Mechanically, Smad6 interacts directly with PIAS3, and this interaction is
mediated through the Mad homology 2 (MH2) domain of Smad6 and the Ring domain of
PIAS3. Smad6 recruits Smurf1 to facilitate PIAS3 ubiquitination and degradation,
which also depends on the MH2 domain and the PY motif of Smad6. Consequently,
Smad6 reduces PIAS3-mediated STAT3 inhibition and promotes glioma cell growth and
stem-like cell initiation. Moreover, the Smad6 MH2 transducible protein restores
PIAS3 expression and subsequently reduces gliomagenesis. Collectively, we
conclude that nuclear-Smad6 enhances glioma development by inducing PIAS3
degradation and subsequent STAT3 activity upregulation.
PMID- 29950564
TI - Chair Heterogeneity Index: Describing the dose heterogeneity inside the tumor
volume where there is a boost volume.
AB - In this report, Chair Heterogeneity Index (CHI) was introduced to assess the dose
heterogeneity inside the target with a boost volume. CHI was defined by dividing
(V Rx - V Dl ) by (V Dm - V Dh ): V Rx , V Dl , V Dm and V Dh were four points
selected from the target cumulative dose volume histogram curve. The
effectiveness of CHI was validated by assessing the treatment plans for
nasopharyngeal cancer (NPC, 12 cases), breast cancer after breast-conserving
surgery (BC, 10 cases), and stereotactic radiosurgery after whole brain
irradiation (SRS, 9 cases). Our results indicate that both CHI and HI of the
target can distinguish Volumetric Modulated Arc Therapy (VMAT) from Intensity
Modulated Radiation Therapy (IMRT, p < 0.05) while the mean differences in CHI
(NPC 1.16, BC 1.19 and SRS 3.3) were larger than those in HI (NPC 0.03, BC 0.02
and SRS 0.02). In addition, CHI of the combination volume (the target minus the
boost) were statistically higher in VMAT than IMRT in all three kinds of cancer.
In conclusion, CHI was effective in assessing the dose heterogeneity inside a
target containing a boost volume.
PMID- 29950565
TI - Green and facile synthesis of few-layer graphene via liquid exfoliation process
for Lithium-ion batteries.
AB - A green and facile method using jet cavitation (JC) was utilized to prepare few
layer graphene (FLG) derived from artificial graphite delamination without adding
any strong acids and oxidants. The JC method not only provides high quality FLG
with high yield but also demonstrate excellent electrochemical performance as
anode materials for Li-ion batteries. Raman spectroscopy, scanning electron
microscopy (SEM), and transmission electron microscopy (TEM) as well as BET
isotherms and XPS are carried out in this study. The results of atomic force
microscopy (AFM) further revealed that up to 85% of the prepared FLG were less
than 10 layers. This exfoliation process happened mainly due to the cavitation
induced intensive tensile stress acting on the layered materials. Electrochemical
measurements demonstrate that graphite anode delivered only 240 mAh/g while FLG
anode achieved more than 322 mAh/g at 5C rate test. These results indicate that
JC method not only paves the way for cheaper and safer production of graphene but
also holds great potential applications in energy-related technology.
PMID- 29950567
TI - Vegetation succession influences soil carbon sequestration in coastal alkali
saline soils in southeast China.
AB - The area of saline soils accounts for 8% of the earth's surface, making these
soils an important terrestrial carbon sink. Soil organic carbon (SOC), microbial
biomass carbon (MBC), dissolved organic carbon (DOC), soil enzyme activity, and
soil bacterial abundance and biodiversity were measured in four successive
coastal tidal flat ecosystems representing: bare saline soil (BS), Suaeda glauca
land (SL), Imperata cylindrica grassland (IG), and Jerusalem artichoke field
(JF). A decrease in soil salt content resulted in increased SOC content. With
vegetation succession, MBC and DOC concentrations showed a positive trend, and
activities of soil urease, catalase, invertase and alkaline phosphatase
increased. A next-generation, Illumina-based sequencing approach showed that
Proteobacteria, Acidobacteria, Chloroflexi, Bacteroidetes, Gemmatimonadetes,
Actinobacteria, Nitrospirae and Planctomycetes were the dominant bacterial
communities (a total of 597 taxa were detected, and 27 genera showed significant
differences among the vegetation communities). Bacterial diversity at two soil
depths was enhanced with the succession of vegetation ecosystems, with the
increases in operational taxonomic units (OTUs) and the Shannon and Chao1 indices
ranked in the order: JF > IG > SL > BS. The SOC and C/N were the most determinant
factors influencing diversity of bacterial communities in the succession
ecosystems.
PMID- 29950566
TI - Structural basis of the correct subunit assembly, aggregation, and intracellular
degradation of nylon hydrolase.
AB - Nylon hydrolase (NylC) is initially expressed as an inactive precursor (36 kDa).
The precursor is cleaved autocatalytically at Asn266/Thr267 to generate an active
enzyme composed of an alpha subunit (27 kDa) and a beta subunit (9 kDa). Four
alphabeta heterodimers (molecules A-D) form a doughnut-shaped quaternary
structure. In this study, the thermostability of the parental NylC was altered by
amino acid substitutions located at the A/D interface (D122G/H130Y/D36A/L137A) or
the A/B interface (E263Q) and spanned a range of 47 degrees C. Considering
structural, biophysical, and biochemical analyses, we discuss the structural
basis of the stability of nylon hydrolase. From the analytical centrifugation
data obtained regarding the various mutant enzymes, we conclude that the assembly
of the monomeric units is dynamically altered by the mutations. Finally, we
propose a model that can predict whether the fate of the nascent polypeptide will
be correct subunit assembly, inappropriate protein-protein interactions causing
aggregation, or intracellular degradation of the polypeptide.
PMID- 29950569
TI - Focusing on mitochondrial form and function.
PMID- 29950568
TI - The mitochondrial DNA polymerase gamma degrades linear DNA fragments precluding
the formation of deletions.
AB - Double-strand breaks in the mitochondrial DNA (mtDNA) result in the formation of
linear fragments that are rapidly degraded. However, the identity of the
nuclease(s) performing this function is not known. We found that the exonuclease
function of the mtDNA polymerase gamma (POLG) is required for this rapid
degradation of mtDNA fragments. POLG is recruited to linearized DNA fragments in
an origin of replication-independent manner. Moreover, in the absence of POLG
exonuclease activity, the prolonged existence of mtDNA linear fragments leads to
increased levels of mtDNA deletions, which have been previously identified in the
mutator mouse, patients with POLG mutations and normal aging.
PMID- 29950570
TI - Mechanisms and impact of altered tumour mechanics.
AB - The physical characteristics of tumours are intricately linked to the tumour
phenotype and difficulties during treatment. Many factors contribute to the
increased stiffness of tumours; from increased matrix deposition, matrix
remodelling by forces from cancer cells and stromal fibroblasts, matrix
crosslinking, increased cellularity, and the build-up of both solid and
interstitial pressure. Increased stiffness then feeds back to increase tumour
invasiveness and reduce therapy efficacy. Increased understanding of this
interplay is offering new therapeutic avenues.
PMID- 29950571
TI - Mitochondrial dynamics in adaptive and maladaptive cellular stress responses.
PMID- 29950572
TI - The multifaceted contributions of mitochondria to cellular metabolism.
AB - Although classically appreciated for their role as the powerhouse of the cell,
the metabolic functions of mitochondria reach far beyond bioenergetics. In this
Review, we discuss how mitochondria catabolize nutrients for energy, generate
biosynthetic precursors for macromolecules, compartmentalize metabolites for the
maintenance of redox homeostasis and function as hubs for metabolic waste
management. We address the importance of these roles in both normal physiology
and in disease.
PMID- 29950573
TI - Water immobilization by glass microspheres affects biological activity.
AB - We recently reported that the water holding capacity of myofibrillar protein
hydrogels could be increased upon addition of small amounts of microparticles,
particularly glass microspheres. Glass microspheres were found to decrease the
spin-spin relaxation time (T2) of water protons in the gels, which was
interpreted as enhanced water binding by the glass. We were thus interested in
determining whether the observed effects on water proton relaxation were a direct
consequence of water-glass interactions. Here we show how glass microspheres
reduce the mobility of pure water, reflected in large decreases in the T2 of
water protons, decreases in the self-diffusion coefficient of water molecules, a
lower water activity, and strengthening of O-H bonds. Even though glass is
considered an inert material, glass microspheres were shown to inhibit the growth
of human embryonic kidney cells, and stimulate or inhibit the growth of leukemia
and monocytic lymphoma cells in vitro, depending on dose and time. The
germination of alfalfa seeds and the growth of E.coli cells were also inhibited
upon exposure to glass microspheres. This work indicates that the properties and
behavior of materials, even ones considered inert, can be affected by their size.
These observations suggest possible toxicological consequences of exposure to
microparticles, but also open us possibilities to affect cellular/organism
function via modulation of macromolecular hydration.
PMID- 29950574
TI - Strengthening non-communicable disease policy with lessons from Bhutan: linking
gross national happiness and health policy action.
AB - There is growing global interest in Gross National Happiness (GNH) as a metric to
capture population well-being and economic development. Empirical evidence
suggests that health is necessary for achievement of happiness. The growing
epidemic of non-communicable diseases (NCDs) threatens to undermine the
achievement of GNH. We analyze synergies between current policy priorities and
the institutional mechanism for GNH and the Global NCD Action Plan 2013-2020 that
has informed Bhutan's approach to NCDs. We identify strategic policy
opportunities to strengthen outcomes for both policy areas. Lessons from Bhutan
also suggest strategic opportunities to address NCDs in other countries where
happiness is on the national agenda, or where action on NCDs could be improved
through engagement between health and other sectors, especially where ways to
promote and measure GNH (population well-being) already exist.
PMID- 29950575
TI - Energy poverty in healthcare facilities: a "silent barrier" to improved
healthcare in sub-Saharan Africa.
AB - This paper addresses an important topic, energy poverty in healthcare facilities.
We try to provide an interesting perspective on bringing together two SDGs. The
SDG 7, which seeks to ensure access to affordable, sustainable, and modern energy
for all, is interlinked with Goal 3 on Health. The literature studies as well as
data on the subject are sparse. Nevertheless, a systematic documentation of the
levels and variation in access to energy at the health-facility level is
important for designing effective policies to improve the quality of healthcare
and the ultimate health of the population. Using the 2012-2013 Senegal Service
Provision Assessment (SCSPA), we assessed energy access in health facilities and
health systems' performance. Data were also geocoded using ArcGIS 10.3 to give a
snapshot of the situation.
PMID- 29950576
TI - Coccolith dissolution within copepod guts affects fecal pellet density and
sinking rate.
AB - The most common biomineral produced in the contemporary ocean is calcium
carbonate, including the polymorph calcite produced by coccolithophores. The
surface waters of the ocean are supersaturated with respect to calcium carbonate.
As a result, particulate inorganic carbon (PIC), such as calcite coccoliths, is
not expected thermodynamically to dissolve in waters above the lysocline (~4500
6000 m). However, observations indicate that up to 60-80% of calcium carbonate is
lost in the upper 500-1000 m of the ocean. This is hypothesized to occur in
microenvironments with reduced saturation states, such as zooplankton guts. Using
a new application of the highly precise 14C microdiffusion technique, we show
that following a period of starvation, up to 38% of ingested calcite dissolves in
copepod guts. After continued feeding, our data show the gut becomes increasingly
buffered, which limits further dissolution; this has been termed the Tums
hypothesis (after the drugstore remedy for stomach acid). As less calcite
dissolves in the gut and is instead egested in fecal pellets, the fecal pellet
sinking rates double, with corresponding increases in pellet density. Our results
empirically demonstrate that zooplankton guts can facilitate calcite dissolution
above the chemical lysocline, and that carbon export through fecal pellet
production is variable, based on the feeding history of the copepod.
PMID- 29950577
TI - Gp41 dynamically interacts with the TCR in the immune synapse and promotes early
T cell activation.
AB - The HIV-1 glycoprotein gp41 critically mediates CD4+ T-cell infection by HIV-1
during viral entry, assembly, and release. Although multiple immune-regulatory
activities of gp41 have been reported, the underlying mechanisms of these
activities remain poorly understood. Here we employed multi-colour single
molecule localization microscopy (SMLM) to resolve interactions of gp41 proteins
with cellular proteins at the plasma membrane (PM) of fixed and live CD4+ T-cells
with resolution of ~20-30 nm. We observed that gp41 clusters dynamically
associated with the T cell antigen receptor (TCR) at the immune synapse upon TCR
stimulation. This interaction, confirmed by FRET, depended on the virus clone,
was reduced by the gp41 ectodomain in tight contacts, and was completely
abrogated by mutation of the gp41 transmembrane domain. Strikingly, gp41
preferentially colocalized with phosphorylated TCRs at the PM of activated T
cells and promoted TCR phosphorylation. Gp41 expression also resulted in enhanced
CD69 upregulation, and in massive cell death after 24-48 hrs. Our results shed
new light on HIV-1 assembly mechanisms at the PM of host T-cells and its impact
on TCR stimulation.
PMID- 29950579
TI - Cross-Cultural Evidence for Apparent Racial Outgroup Advantage: Congruence
between Perceived Facial Aggressiveness and Fighting Success.
AB - Research into face processing consistently shows an outgroup disadvantage in
areas such as recognition memory and emotional identification. Potential ingroup
advantage with respect to inferences regarding personality and behavioural
outcomes, on the other hand, has not yet been studied. In the present study, we
used the faces of male professional mixed martial arts (MMA) fighters of apparent
African, European, or mixed-race origin as targets and males from four distant
populations that vary in ethnic composition as perceivers. We compared the
perceivers' inferences about targets' aggressiveness with the fighters' actual
performance in professional MMA championships. Surprisingly, across three distant
populations used in the study (Cameroon, Czech Republic, and Turkey), perceivers'
inferences based on face rating were more congruent with real-world performance
for targets belonging to an apparent racial outgroup (as opposed to ingroup). In
an ethnically mixed population (Brazil), perceivers showed the lowest congruence
for apparently mixed-race targets. It thus seems that the outgroup disadvantage
observed in other face processing domains does not carry over to inferences about
aggressive behavioural outcomes. In fact, it seems that this relationship is, if
anything, reversed.
PMID- 29950580
TI - The Open Translational Science in Schizophrenia (OPTICS) project: an open-science
project bringing together Janssen clinical trial and NIMH data.
AB - Clinical trial data are the gold standard for evaluating pharmaceutical safety
and efficacy. There is an ethical and scientific imperative for transparency and
data sharing to confirm published results and generate new knowledge. The Open
Translational Science in Schizophrenia (OPTICS) Project was an open-science
initiative aggregating Janssen clinical trial and NIH/NIMH data from real-world
studies and trials in schizophrenia. The project aims were to show the value of
using shared data to examine: therapeutic safety and efficacy; disease etiologies
and course; and methods development. The success of project investigators was due
to collaboration from project applications through analyses, with support from
the Harvard Catalyst. Project work was independent of Janssen; all intellectual
property was dedicated to the public. Efforts such as this are necessary to gain
deeper insights into the biology of disease, foster collaboration, and to achieve
the goal of developing better treatments, reducing the overall public health
burden of devastating brain diseases.
PMID- 29950578
TI - The epicardium as a hub for heart regeneration.
AB - After decades of directed research, no effective regenerative therapy is
currently available to repair the injured human heart. The epicardium, a layer of
mesothelial tissue that envelops the heart in all vertebrates, has emerged as a
new player in cardiac repair and regeneration. The epicardium is essential for
muscle regeneration in the zebrafish model of innate heart regeneration, and the
epicardium also participates in fibrotic responses in mammalian hearts. This
structure serves as a source of crucial cells, such as vascular smooth muscle
cells, pericytes, and fibroblasts, during heart development and repair. The
epicardium also secretes factors that are essential for proliferation and
survival of cardiomyocytes. In this Review, we describe recent advances in our
understanding of the biology of the epicardium and the effect of these findings
on the candidacy of this structure as a therapeutic target for heart repair and
regeneration.
PMID- 29950582
TI - An auxin switch for male fertility.
PMID- 29950581
TI - Experimental infection of dromedaries with Middle East respiratory syndrome
Coronavirus is accompanied by massive ciliary loss and depletion of the cell
surface receptor dipeptidyl peptidase 4.
AB - Middle East respiratory syndrome (MERS) represents an important respiratory
disease accompanied by lethal outcome in one-third of human patients. Recent data
indicate that dromedaries represent an important source of infection, although
information regarding viral cell tropism and pathogenesis is sparse. In the
current study, tissues of eight dromedaries receiving inoculation of MERS
Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)
vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS
application (mock vaccination, n = 2), respectively, were investigated. Tissues
were analyzed by histology, immunohistochemistry, immunofluorescence, and
scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries
revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and
macrophages within nasal turbinates and trachea at day four post infection.
Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial
cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14
expressing cells did not co-localize with virus. In addition, virus was
occasionally detected in macrophages. The acute disease was further accompanied
by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to
mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary
monocytes, but overall the expression level was lower in dromedaries. The present
study underlines significant species-specific manifestations of MERS and
highlights ciliary loss as an important finding in dromedaries. The obtained
results promote a better understanding of coronavirus infections, which pose
major health challenges.
PMID- 29950583
TI - Human coronavirus OC43 outbreak in wild chimpanzees, Cote d'Ivoire, 2016.
PMID- 29950584
TI - Cross-species evidence from human and rat brain transcriptome for growth factor
signaling pathway dysregulation in major depression.
AB - An enhanced understanding of the pathophysiology of depression would facilitate
the discovery of new efficacious medications. To this end, we examined
hippocampal transcriptional changes in rat models of disease and in humans to
identify common disease signatures by using a new algorithm for signature-based
clustering of expression profiles. The tool identified a transcriptomic signature
comprising 70 probesets able to discriminate depression models from controls in
both Flinders Sensitive Line and Learned Helplessness animals. To identify
disease-relevant pathways, we constructed an expanded protein network based on
signature gene products and performed functional annotation analysis. We applied
the same workflow to transcriptomic profiles of depressed patients. Remarkably, a
171-probesets transcriptional signature which discriminated depressed from
healthy subjects was identified. Rat and human signatures shared the SCARA5 gene,
while the respective networks derived from protein-based significant interactions
with signature genes contained 25 overlapping genes. The comparison between the
most enriched pathways in the rat and human signature networks identified a
highly significant overlap (p-value: 3.85 * 10-6) of 67 terms including ErbB,
neurotrophin, FGF, IGF, and VEGF signaling, immune responses and insulin and
leptin signaling. In conclusion, this study allowed the identification of a
hippocampal transcriptional signature of resilient or susceptible responses in
rat MDD models which overlapped with gene expression alterations observed in
depressed patients. These findings are consistent with a loss of hippocampal
neural plasticity mediated by altered levels of growth factors and increased
inflammatory responses causing metabolic impairments as crucial factors in the
pathophysiology of MDD.
PMID- 29950585
TI - A hybrid computational approach for efficient Alzheimer's disease classification
based on heterogeneous data.
AB - There is currently a lack of an efficient, objective and systemic approach
towards the classification of Alzheimer's disease (AD), due to its complex
etiology and pathogenesis. As AD is inherently dynamic, it is also not clear how
the relationships among AD indicators vary over time. To address these issues, we
propose a hybrid computational approach for AD classification and evaluate it on
the heterogeneous longitudinal AIBL dataset. Specifically, using clinical
dementia rating as an index of AD severity, the most important indicators (mini
mental state examination, logical memory recall, grey matter and cerebrospinal
volumes from MRI and active voxels from PiB-PET brain scans, ApoE, and age) can
be automatically identified from parallel data mining algorithms. In this work,
Bayesian network modelling across different time points is used to identify and
visualize time-varying relationships among the significant features, and
importantly, in an efficient way using only coarse-grained data. Crucially, our
approach suggests key data features and their appropriate combinations that are
relevant for AD severity classification with high accuracy. Overall, our study
provides insights into AD developments and demonstrates the potential of our
approach in supporting efficient AD diagnosis.
PMID- 29950587
TI - Cancer risk by the subtype of alopecia.
AB - The cancer risk in patients with alopecia areata (AA) or alopecia totalis
(AT)/alopecia universalis (AU) remains unknown. In this study, national
statistical data were used to study the association between these forms of
alopecia and the risk of cancer. We enrolled 668,604 patients who were treated
for alopecia from 2007 to 2014, and age- and sex-matched control subjects. AA and
AT/AU patients had slightly higher overall cancer risks (hazard ratio (HR),
1.043; 95% confidence interval (CI), 1.022-1.065 and HR, 1.07; 95% CI, 1.013
1.129, respectively) than controls, after adjusting for confounding factors. The
risks of oral cavity, esophagus, liver, biliary tract, pancreas, larynx, lung,
kidney, breast, cervix, ovary, uterus, testis, nerve, and skin cancers; and
lymphoma, multiple myeloma, and leukemia, were not increased in alopecia
patients. In AA or AT/AU patients, the only increased risk was that of thyroid
cancer. In AA patients alone, the risks of bladder and prostate cancers were
increased. Thus, the cancer risks varied by the alopecia subtype. Careful
monitoring is needed to explore if the actual risks of thyroid, bladder, and
prostate cancers are increased in alopecia patients.
PMID- 29950586
TI - Risk of weight gain for specific antipsychotic drugs: a meta-analysis.
AB - People with schizophrenia are at considerably higher risk of cardiometabolic
morbidity than the general population. Second-generation antipsychotic drugs
contribute to that risk partly through their weight gain effects, exacerbating an
already high burden of disease. While standard 'as-randomized' analyses of
clinical trials provide valuable information, they ignore adherence patterns
across treatment arms, confounding estimates of realized treatment exposure on
outcome. We assess the effect of specific second-generation antipsychotics on
weight gain, defined as at least a 7% increase in weight from randomization,
using a Bayesian hierarchical model network meta-analysis with individual patient
level data. Our data consisted of 14 randomized clinical trials contributing 5923
subjects (mean age = 39 [SD = 12]) assessing various combinations of olanzapine
(n = 533), paliperidone (n = 3482), risperidone (n = 540), and placebo (n =
1368). The median time from randomization to dropout or trial completion was 6
weeks (range: 0-60 weeks). The unadjusted probability of weight gain in the
placebo group was 4.8% across trials. For each 10 g chlorpromazine equivalent
dose increase in olanzapine, the odds of weight gain increased by 5 (95% credible
interval: 1.4, 5.3); the effect of risperidone (odds ratio = 1.6 [0.25, 9.1]) was
estimated with considerable uncertainty but no different from paliperidone (odds
ratio = 1.3 [1.2, 1.5]).
PMID- 29950588
TI - Noise-induced stabilization and fixation in fluctuating environment.
AB - The dynamics of a two-species community of N competing individuals are
considered, with an emphasis on the role of environmental variations that affect
coherently the fitness of entire populations. The chance of fixation of a mutant
(or invading) population is calculated as a function of its mean relative
fitness, the amplitude of fitness variations and their typical duration. We
emphasize the distinction between the case of pairwise competition and the case
of global competition; in the latter a noise-induced stabilization mechanism
yields a higher chance of fixation for a single mutant. This distinction becomes
dramatic in the weak selection regime, where the chance of fixation for a single
deleterious mutant is an N-independent constant for global competition and decays
like (ln N)-1 in the pairwise competition case. A Wentzel-Kramers-Brillouin (WKB)
technique yields a general formula for the chance of fixation of a deleterious
mutant in the strong selection regime. The possibility of long-term persistence
of large [[Formula: see text](N)] suboptimal (and extinction-prone) populations
is discussed, as well as its relevance to stochastic tunneling between fitness
peaks.
PMID- 29950591
TI - DKK3 loss induces opposing effects.
PMID- 29950589
TI - A promiscuous cytochrome P450 aromatic O-demethylase for lignin bioconversion.
AB - Microbial aromatic catabolism offers a promising approach to convert lignin, a
vast source of renewable carbon, into useful products. Aryl-O-demethylation is an
essential biochemical reaction to ultimately catabolize coniferyl and sinapyl
lignin-derived aromatic compounds, and is often a key bottleneck for both native
and engineered bioconversion pathways. Here, we report the comprehensive
characterization of a promiscuous P450 aryl-O-demethylase, consisting of a
cytochrome P450 protein from the family CYP255A (GcoA) and a three-domain
reductase (GcoB) that together represent a new two-component P450 class. Though
originally described as converting guaiacol to catechol, we show that this system
efficiently demethylates both guaiacol and an unexpectedly wide variety of lignin
relevant monomers. Structural, biochemical, and computational studies of this
novel two-component system elucidate the mechanism of its broad substrate
specificity, presenting it as a new tool for a critical step in biological lignin
conversion.
PMID- 29950592
TI - The case for nonsurgical therapy of nonmetastatic penile cancer.
AB - Invasive squamous cell carcinoma (SCC) of the penis is almost always treated with
surgical therapy at the primary site. However, almost all other SCC primary
sites, such as anal, vulvar, uterine cervix, head and neck, and oesophagus, and
their involved nodal basins, can be successfully treated with radiotherapy or
combined chemotherapy and radiation, reserving surgery as a salvage option.
Review of the penile cancer literature and examination of data from more common
SCC primary sites make a case for complete organ preservation of the penis using
definitive combined chemotherapy and radiation, reserving surgical therapies as
salvage options.
PMID- 29950590
TI - BALB/c mice infected with DENV-2 strain 66985 by the intravenous route display
injury in the central nervous system.
AB - Dengue is a mild flu-like arboviral illness caused by dengue virus (DENV) that
occurs in tropical and subtropical countries. An increasing number of reports
have been indicating that dengue is also associated to neurological
manifestations, however, little is known regarding the neuropathogenesis of the
disease. Here, using BALB/c mice intravenously infected with DENV-2 strain 66985,
we demonstrated that the virus is capable of invading and damaging the host's
central nervous system (CNS). Brain and cerebellum of infected animals revealed
histological alterations such as the presence of inflammatory infiltrates,
thickening of pia matter and disorganization of white matter. Additionally, it
was also seen that infection lead to altered morphology of neuroglial cells and
apoptotic cell death. Such observations highlighted possible alterations that
DENV may promote in the host's CNS during a natural infection, hence, helping us
to better understand the neuropathological component of the disease.
PMID- 29950593
TI - High Modularity Creates Scaling Laws.
AB - Scaling laws have been observed in many natural and engineered systems. Their
existence can give useful information about the growth or decay of one
quantitative feature in terms of another. For example, in the field of city
analytics, it is has been fruitful to compare some urban attribute, such as
energy usage or wealth creation, with population size. In this work, we use
network science and dynamical systems perspectives to explain that the observed
scaling laws, and power laws in particular, arise naturally when some feature of
a complex system is measured in terms of the system size. Our analysis is based
on two key assumptions that may be posed in graph theoretical terms. We assume
(a) that the large interconnection network has a well-defined set of communities
and (b) that the attribute under study satisfies a natural continuity-type
property. We conclude that precise mechanistic laws are not required in order to
explain power law effects in complex systems-very generic network-based rules can
reproduce the behaviors observed in practice. We illustrate our results using
Twitter interaction between accounts geolocated to the city of Bristol, UK.
PMID- 29950594
TI - Automated detection and manipulation of sleep in C. elegans reveals
depolarization of a sleep-active neuron during mechanical stimulation-induced
sleep deprivation.
AB - Across species, sleep is characterized by a complex architecture. Sleep
deprivation is a classic method to study the consequences of sleep loss, which
include alterations in the activity of sleep circuits and detrimental
consequences on well being. Automating the observation and manipulation of sleep
is advantageous to study its regulation and functions. Caenorhabditis elegans
shows sleep behavior similar to other animals that have a nervous system.
However, a method for real-time automatic sleep detection that allows sleep
specific manipulations has not been established for this model animal. Also, our
understanding of how sleep deprivation affects sleep neurons in this system is
incomplete. Here we describe a system for real-time automatic sleep detection of
C. elegans grown in microfluidic devices based on a frame-subtraction algorithm
using a dynamic threshold. As proof of principle for this setup, we used
automated mechanical stimulation to perturb sleep behavior and followed the
activity of the sleep-active RIS neuron. We show that our system can
automatically detect sleep bouts and deprive worms of sleep. We found that
mechanical stimulation generally leads to the activation of the sleep-active RIS
neuron, and this stimulation-induced RIS depolarization is most prominent during
sleep deprivation.
PMID- 29950595
TI - Advocating for the consumer: clinical confirmation of all direct-to-consumer raw
data alterations remains critical.
PMID- 29950596
TI - Dissociable neural mechanisms track evidence accumulation for selection of
attention versus action.
AB - Decision-making is typically studied as a sequential process from the selection
of what to attend (e.g., between possible tasks, stimuli, or stimulus attributes)
to which actions to take based on the attended information. However, people often
process information across these various levels in parallel. Here we scan
participants while they simultaneously weigh how much to attend to two dynamic
stimulus attributes and what response to give. Regions of the prefrontal cortex
track information about the stimulus attributes in dissociable ways, related to
either the predicted reward (ventromedial prefrontal cortex) or the degree to
which that attribute is being attended (dorsal anterior cingulate cortex, dACC).
Within the dACC, adjacent regions track correlates of uncertainty at different
levels of the decision, regarding what to attend versus how to respond. These
findings bridge research on perceptual and value-based decision-making,
demonstrating that people dynamically integrate information in parallel across
different levels of decision-making.
PMID- 29950597
TI - Controllable water surface to underwater transition through electrowetting in a
hybrid terrestrial-aquatic microrobot.
AB - Several animal species demonstrate remarkable locomotive capabilities on land, on
water, and under water. A hybrid terrestrial-aquatic robot with similar
capabilities requires multimodal locomotive strategies that reconcile the
constraints imposed by the different environments. Here we report the development
of a 1.6 g quadrupedal microrobot that can walk on land, swim on water, and
transition between the two. This robot utilizes a combination of surface tension
and buoyancy to support its weight and generates differential drag using passive
flaps to swim forward and turn. Electrowetting is used to break the water surface
and transition into water by reducing the contact angle, and subsequently
inducing spontaneous wetting. Finally, several design modifications help the
robot overcome surface tension and climb a modest incline to transition back onto
land. Our results show that microrobots can demonstrate unique locomotive
capabilities by leveraging their small size, mesoscale fabrication methods, and
surface effects.
PMID- 29950598
TI - Nogo-A inactivation improves visual plasticity and recovery after retinal injury.
AB - Myelin-associated proteins such as Nogo-A are major inhibitors of neuronal
plasticity that contribute to permanent neurological impairments in the injured
CNS. In the present study, we investigated the influence of Nogo-A on visual
recovery after retinal injuries in mice. Different doses of N-methyl-D-aspartate
(NMDA) were injected in the vitreous of the left eye to induce retinal neuron
death. The visual function was monitored using the optokinetic response (OKR) as
a behavior test, and electroretinogram (ERG) and local field potential (LFP)
recordings allowed to assess changes in retinal and cortical neuron activity,
respectively. Longitudinal OKR follow-ups revealed reversible visual deficits
after injection of NMDA <= 1 nmole in the left eye and concomitant functional
improvement in the contralateral visual pathway of the right eye that was let
intact. Irreversible OKR loss observed with NMDA >= 2 nmol was correlated with
massive retinal cell death and important ERG response decline. Strikingly, the
OKR mediated by injured and intact eye stimulation was markedly improved in Nogo
A KO mice compared with WT animals, suggesting that the inactivation of Nogo-A
promotes visual recovery and plasticity. Moreover, OKR improvement was associated
with shorter latency of the N2 wave of Nogo-A KO LFPs relative to WT animals.
Strikingly, intravitreal injection of anti-Nogo-A antibody (11C7) in the injured
eye exerted positive effects on cortical LFPs. This study presents the intrinsic
ability of the visual system to recover from NMDA-induced retinal injury and its
limitations. Nogo-A neutralization may promote visual recovery in retinal
diseases such as glaucoma.
PMID- 29950599
TI - Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and
variance increase through lifetimes and generations.
AB - Vital mitochondrial DNA (mtDNA) populations exist in cells and may consist of
heteroplasmic mixtures of mtDNA types. The evolution of these heteroplasmic
populations through development, ageing, and generations is central to genetic
diseases, but is poorly understood in mammals. Here we dissect these population
dynamics using a dataset of unprecedented size and temporal span, comprising 1947
single-cell oocyte and 899 somatic measurements of heteroplasmy change throughout
lifetimes and generations in two genetically distinct mouse models. We provide a
novel and detailed quantitative characterisation of the linear increase in
heteroplasmy variance throughout mammalian life courses in oocytes and pups. We
find that differences in mean heteroplasmy are induced between generations, and
the heteroplasmy of germline and somatic precursors diverge early in development,
with a haplotype-specific direction of segregation. We develop stochastic theory
predicting the implications of these dynamics for ageing and disease
manifestation and discuss its application to human mtDNA dynamics.
PMID- 29950600
TI - A cylindrical assembly model and dynamics of the Ebola virus VP40 structural
matrix.
AB - The Ebola filovirus causes severe hemorrhagic fever with a high fatality rate in
humans. The primary structural matrix protein VP40 displays transformer-protein
characteristics and exists in different conformational and oligomeric states.
VP40 plays crucial roles in viral assembly and budding at the plasma membrane of
the infected cells and is capable of forming virus-like particles without the
need for other Ebola proteins. However, no experimental three-dimensional
structure for any filovirus VP40 cylindrical assembly matrix is currently
available. Here, we use a protein-protein docking approach to develop cylindrical
assembly models for an Ebola virion and also for a smaller structural matrix that
does not contain genetic material. These models match well with the 2D averages
of cryo-electron tomograms of the authentic virion. We also used all-atom
molecular dynamics simulations to investigate the stability and dynamics of the
cylindrical models and the interactions between the side-by-side hexamers to
determine the amino acid residues that are especially important for stabilizing
the hexamers in the cylindrical ring configuration matrix assembly. Our models
provide helpful information to better understand the assembly processes of
filoviruses and such structural studies may also lead to the design and
development of antiviral drugs.
PMID- 29950601
TI - Personalising adherence-enhancing interventions using a smart inhaler in patients
with COPD: an exploratory cost-effectiveness analysis.
AB - Four inhaler adherence clusters have been identified using the INCA audio device
in COPD patients: (1) regular use/good technique, (2) regular use/frequent
technique errors, (3) irregular use/good technique, and (4) irregular
use/frequent technique errors. Their relationship with healthcare utilization and
mortality was established, but the cost-effectiveness of adherence-enhancing
interventions is unknown. In this exploratory study, we aimed to estimate the
potential cost-effectiveness of reaching optimal adherence in the three
suboptimal adherence clusters, i.e., a theoretical shift of clusters 2, 3, and 4
to cluster 1. Cost-effectiveness was estimated over a 5-year time horizon using
the Irish healthcare payer perspective. We used a previously developed COPD
health-economic model that was updated with INCA trial data and Irish national
economic and epidemiological data. For each cluster, interventions would result
in additional quality-adjusted life years gained at reasonable investment. Cost
effectiveness was most favorable in cluster 3, with possible cost savings of
?845/annum/person.
PMID- 29950604
TI - American College of Gastroenterology Monograph on Management of Irritable Bowel
Syndrome.
PMID- 29950602
TI - Reducing histone acetylation rescues cognitive deficits in a mouse model of
Fragile X syndrome.
AB - Fragile X syndrome (FXS) is the most prevalent inherited intellectual disability,
resulting from a loss of fragile X mental retardation protein (FMRP). Patients
with FXS suffer lifelong cognitive disabilities, but the function of FMRP in the
adult brain and the mechanism underlying age-related cognitive decline in FXS is
not fully understood. Here, we report that a loss of FMRP results in increased
protein synthesis of histone acetyltransferase EP300 and ubiquitination-mediated
degradation of histone deacetylase HDAC1 in adult hippocampal neural stem cells
(NSCs). Consequently, FMRP-deficient NSCs exhibit elevated histone acetylation
and age-related NSC depletion, leading to cognitive impairment in mature adult
mice. Reducing histone acetylation rescues both neurogenesis and cognitive
deficits in mature adult FMRP-deficient mice. Our work reveals a role for FMRP
and histone acetylation in cognition and presents a potential novel therapeutic
strategy for treating adult FXS patients.
PMID- 29950603
TI - The pharmacological perturbation of brain zinc impairs BDNF-related signaling and
the cognitive performances of young mice.
AB - Zinc (Zn2+) is a pleiotropic modulator of the neuronal and brain activity. The
disruption of intraneuronal Zn2+ levels triggers neurotoxic processes and affects
neuronal functioning. In this study, we investigated how the pharmacological
modulation of brain Zn2+ affects synaptic plasticity and cognition in wild-type
mice. To manipulate brain Zn2+ levels, we employed the Zn2+ (and copper) chelator
5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ). CQ was administered for two
weeks to 2.5-month-old (m.o.) mice, and effects studied on BDNF-related
signaling, metalloproteinase activity as well as learning and memory
performances. CQ treatment was found to negatively affect short- and long-term
memory performances. The CQ-driven perturbation of brain Zn2+ was found to reduce
levels of BDNF, synaptic plasticity-related proteins and dendritic spine density
in vivo. Our study highlights the importance of choosing "when", "where", and
"how much" in the modulation of brain Zn2+ levels. Our findings confirm the
importance of targeting Zn2+ as a therapeutic approach against neurodegenerative
conditions but, at the same time, underscore the potential drawbacks of reducing
brain Zn2+ availability upon the early stages of development.
PMID- 29950605
TI - Serotonin and YAP/VGLL4 Balance Correlated with Progression and Poor Prognosis of
Hepatocellular Carcinoma.
AB - YAP-TEAD complex plays an important role in tumorigenesis. 5-HT is proved to
upregulate YAP expression by our previous study and VGLL4 is found to compete
with YAP for binding to TEAD in several of cancers. Here, we investigated whether
5-HT could affect progression and prognosis of hepatocellular carcinoma (HCC)
patients and regulate YAP/VGLL4 balance. We found that 5-HT and YAP/VGLL4 ratio
were higher in HCC patients and closely related with progression and poor
prognosis. Furthermore, 5-HT level, YAP/VGLL4 ratio and tumor size were proved as
independent risk factors of HCC patients in our study. Based on the independent
risk factors, nomogram was established to exactly predict prognosis of HCC
patients. Additionally, the study revealed that a higher total point of the
nomogram was closely correlated with poorer prognosis. As a result, 5-HT might
contribute to the progression and poor prognosis of hepatocellular carcinoma via
regulating YAP/VGLL4 balance. Therefore, the established nomogram based on the
independent risk factors may become an important part of HCC prediction system
and YAP/VGLL4 balance may be a potential therapeutic target in future.
PMID- 29950606
TI - Positron Annihilation Studies on Chemically Synthesized FeCo Alloy.
AB - Equiatomic flower-like FeCo magnetic nanoparticles are synthesized through a
modified one-pot polyol technique. The as-prepared samples are annealed at 700
and 800 degrees C under reducing atmosphere. The saturation magnetization and
coercivity of the flower-like FeCo are found to be 198 (1) emu/g and 243 (10) Oe
respectively. The magnetic properties of FeCo approach the bulk behavior with
annealing. Positron lifetime studies on the chemically synthesized equiatomic
FeCo magnetic nanoparticles with flower-like morphology are reported and compared
with Fe, Co and FeCo annealed at various temperatures. The FeCo is characterized
by different lifetime components corresponding to positron annihilation events in
vacancies and various open volume defects due to their unique morphology. The
studies suggest defects arising out of cluster vacancies and interpetal gap that
reduce on annealing. The average pore size obtained from positron annihilation
studies closely matches with the interpetal distance obtained from the electron
microscopic analysis for the flower-like FeCo.
PMID- 29950607
TI - Optically-Monitored Nanopore Fabrication Using a Focused Laser Beam.
AB - Solid-state nanopores (ssNPs) are extremely versatile single-molecule sensors and
their potential have been established in numerous biomedical applications.
However, the fabrication of ssNPs remains the main bottleneck to their widespread
use. Herein, we introduce a rapid and localizable ssNPs fabrication method based
on feedback-controlled optical etching. We show that a focused blue laser beam
irreversibly etches silicon nitride (SiNx) membranes in solution. Furthermore,
photoluminescence (PL) emitted from the SiNx is used to monitor the etching
process in real-time, hence permitting rate adjustment. Transmission electron
microscopy (TEM) images of the etched area reveal an inverted Gaussian thickness
profile, corresponding to the intensity point spread function of the laser beam.
Continued laser exposure leads to the opening of a nanopore, which can be
controlled to reproducibly fabricate nanopores of different sizes. The optically
formed ssNPs exhibit electrical noise on par with TEM-drilled pores, and
translocate DNA and proteins readily. Notably, due to the localized thinning, the
laser-drilled ssNPs exhibit highly suppressed background PL and improved spatial
resolution. Given the total control over the nanopore position, this easily
implemented method is ideally suited for electro-optical sensing and opens up the
possibility of fabricating large nanopore arrays in situ.
PMID- 29950609
TI - Viperin breaks viral chains.
PMID- 29950608
TI - Maternal Vitamin D Prevents Abnormal Dopaminergic Development and Function in a
Mouse Model of Prenatal Immune Activation.
AB - Dysfunction in dopamine (DA) systems is a prominent feature in schizophrenia
patients and may result from the abnormal development of mesencephalic (mes)DA
systems. Maternal immune activation (MIA) and developmental vitamin D (DVD)
deficiency both induce schizophrenia-relevant dopaminergic abnormalities in adult
offspring. In this study, we investigated whether maternal administration of the
vitamin D hormone (1,25OHD, VITD) could prevent MIA-induced abnormalities in DA
related behaviors and mesDA development. We administrated the viral mimetic
polyriboinosinic-polyribocytidylic (poly (I:C)) simultaneously with 1,25OHD
and/or their vehicles, to pregnant mouse dams at gestational day 9. Maternal
treatment with VITD prevented MIA-induced hypersensitivity to acute DA
stimulation induced by amphetamine, whereas it failed to block prepulse
inhibition deficiency in MIA-exposed offspring. MIA and VITD both reduced fetal
mesDA progenitor (Lmx1a + Sox2+) cells, while VITD treatment increased the number
of mature (Nurr1 + TH+) mesDA neurons. Single-cell quantification of protein
expression showed that VITD treatment increased the expression of Lmx1a, Nurr1
and TH in individual mesDA cells and restored normal mesDA positioning. Our data
demonstrate that VITD prevents abnormal dopaminergic phenotypes in MIA offspring
possibly via its early neuroprotective actions on fetal mesDA neurons. Maternal
supplementation with the dietary form of vitamin D, cholecalciferol may become a
valuable strategy for the prevention of MIA-induced neurodevelopmental
abnormalities.
PMID- 29950611
TI - S100B and LDH as early prognostic markers for response and overall survival in
melanoma patients treated with anti-PD-1 or combined anti-PD-1 plus anti-CTLA-4
antibodies.
AB - BACKGROUND: Immunotherapy with PD-1 antibodies has greatly increased prognosis of
patients with advanced melanoma. Identifying biomarkers that predict overall
survival (OS) and response to immunotherapy is important. METHODS: OS and best
overall response according to RECIST version 1.1 were analysed, and S100B and
lactate dehydrogenase (LDH) serum levels were assessed retrospectively in 152
patients treated with anti-PD-1, and in 86 patients treated with anti-PD-1 plus
anti-CTLA-4 antibodies at University Hospital Tuebingen, Germany. RESULTS: In the
pembrolizumab group, patients with elevated baseline S100B or LDH exhibited
significantly impaired OS compared with patients with normal S100B (1-year OS:
51.1% vs 83.1%, log-rank P < .0001) and normal LDH (1-year OS: 44.4% vs 80.8%, P
= .00022), respectively. LDH increases of >25% and S100B increases of >145%
compared to baseline were significantly associated with impaired OS (both P <
.0001). In patients treated with ipilimumab and nivolumab, baseline S100B and
increasing S100B levels of >145% as well as baseline LDH were associated with
impaired OS (P < .0001, P = .00060, and P = .0050, respectively), whereas
increasing LDH of >25% was not (P = .64). CONCLUSIONS: S100B could serve as a
strong baseline marker for OS in melanoma patients receiving anti-PD-1 therapy.
Rising S100B levels during the first weeks of therapy could help guide treatment
decisions.
PMID- 29950610
TI - Proton irradiation orchestrates macrophage reprogramming through NFkappaB
signaling.
AB - Tumor-associated macrophages (TAMs) represent potential targets for anticancer
treatments as these cells play critical roles in tumor progression and frequently
antagonize the response to treatments. TAMs are usually associated to an M2-like
phenotype, characterized by anti-inflammatory and protumoral properties. This
phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory,
phagocytic, and antitumoral functions. As macrophages hold a high plasticity,
strategies to orchestrate the reprogramming of M2-like TAMs towards a M1
antitumor phenotype offer potential therapeutic benefits. One of the most used
anticancer treatments is the conventional X-ray radiotherapy (RT), but this
therapy failed to reprogram TAMs towards an M1 phenotype. While protontherapy is
more and more used in clinic to circumvent the side effects of conventional RT,
the effects of proton irradiation on macrophages have not been investigated yet.
Here we showed that M1 macrophages (THP-1 cell line) were more resistant to
proton irradiation than unpolarized (M0) and M2 macrophages, which correlated
with differential DNA damage detection. Moreover, proton irradiation-induced
macrophage reprogramming from M2 to a mixed M1/M2 phenotype. This reprogramming
required the nuclear translocation of NFkappaB p65 subunit as the inhibition of
IkappaBalpha phosphorylation completely reverted the macrophage re-education.
Altogether, the results suggest that proton irradiation promotes NFkappaB
mediated macrophage polarization towards M1 and opens new perspectives for
macrophage targeting with charged particle therapy.
PMID- 29950613
TI - Biomarkers for individualized dosage adjustments in immunosuppressive therapy
using calcineurin inhibitors after organ transplantation.
AB - Calcineurin inhibitors (CNIs), such as cyclosporine A and tacrolimus, are widely
used immunosuppressive agents for the prevention of post-transplantation
rejection and have improved 1-year graft survival rates by up to 90%. However,
CNIs can induce severe reactions, such as acute or chronic allograft nephropathy,
hypertension, and neurotoxicity. Because CNIs have varied bioavailabilities,
narrow therapeutic ranges, and individual propensities for toxic effects,
therapeutic drug monitoring is necessary for all CNIs. Identifying the genetic
polymorphisms in drug-metabolizing enzymes will help to determine personalized
dosage regimens for CNIs, as CNIs are substrates for CYP3A5 and P-glycoprotein (P
gp, MDR1). CNIs are often concomitantly administered with voriconazole or proton
pump inhibitors (PPIs), giving rise to drug interaction problems. Voriconazole
and PPIs can increase the blood concentrations of CNIs, and both are primarily
metabolized by CYP2C19. Thus, it is expected that interactions between CNIs and
voriconazole or PPI would be affected by CYP2C19 and CYP3A5 polymorphisms. CNI
induced acute kidney injury (AKI) is a serious complication of transplantations.
Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1
(KIM-1) are noninvasive urinary biomarkers that are believed to be highly
sensitive to CNI-induced AKI. In this article, we review the adverse events and
pharmacokinetics of CNIs and the biomarkers related to CNIs, including CYP3A5,
CYP2C19, MDR1, NGAL, and KIM-1. We hope that these data will help to identify the
optimal biomarkers for monitoring CNI-based immunosuppressive therapy after organ
transplantation.
PMID- 29950614
TI - Design and evaluation of glomerulus mesangium-targeted PEG-PLGA nanoparticles
loaded with dexamethasone acetate.
AB - Mesangial proliferative glomerulonephritis (MsPGN), one of the most common
glomerulonephritis pathological types, often leads to end-stage renal disease
over a prolonged period. But the current treatment of MsPGN is non-specific and
causes serious side effects, thus novel therapeutics and targeting strategies are
urgently demanded. By combining the advantages of PEG-PLGA nanoparticles and the
size selection mechanism of renal glomerulus, we designed and developed a novel
PEG-PLGA nanoparticle delivery system capable of delivering dexamethasone acetate
(A-DEX) into glomerular mesangium. We determined that 90 nm was the optimum size
to encapsulate A-DEX for glomerular mesangium targeting based on the size
selection mechanism of glomerulus. After intravenous administration in rats, 90
nm DiD-loaded NPs were found to accumulate to a greater extent in the kidney and
kidney cortex compared with the free DiD solution. The 90 nm A-DEX NPs are also
more stable at room temperature and showed a sustained release pattern. In rat
glomerular mesangial cells (HBZY-1) in vitro, we found that the uptake of 90 nm A
DEX NPs was both temperature-dependent and energe-dependent, and they were mostly
engulfed via clathrin-dependent endocytosis pathways. In summary, we have
successfully developed a glomerular mesangium-targeted PEG-PLGA NPs, which is
potential for the treatment of MsPGN.
PMID- 29950615
TI - Pharmacological activation of REV-ERBalpha represses LPS-induced microglial
activation through the NF-kappaB pathway.
AB - REV-ERBalpha, the NR1D1 (nuclear receptor subfamily 1, group D, member 1) gene
product, is a dominant transcriptional silencer that represses the expression of
genes involved in numerous physiological functions, including circadian rhythm,
inflammation, and metabolism, and plays a crucial role in maintaining immune
functions. Microglia-mediated neuroinflammation is tightly associated with
various neurodegenerative diseases and psychiatric disorders. However, the role
of REV-ERBalpha in neuroinflammation is largely unclear. In this study, we
investigated whether and how pharmacological activation of REV-ERBalpha affected
lipopolysaccharide (LPS)-induced neuroinflammation in mouse microglia in vitro
and in vivo. In BV2 cells or primary mouse cultured microglia, application of REV
ERBalpha agonist GSK4112 or SR9011 dose-dependently suppressed LPS-induced
microglial activation through the nuclear factor kappa B (NF-kappaB) pathway. In
BV2 cells, pretreatment with GSK4112 inhibited LPS-induced phosphorylation of the
inhibitor of NF-kappaB alpha (IkappaBalpha) kinase (IkappaK), thus restraining
the phosphorylation and degradation of IkappaBalpha, and blocked the nuclear
translocation of p65, a NF-kappaB subunit, thereby suppressing the expression and
secretion of the proinflammatory cytokines, such as interleukin 6 (IL-6) and
tumor necrosis factor alpha (TNFalpha). Moreover, REV-ERBalpha agonist-induced
inhibition on neuroinflammation protected neurons from microglial activation
induced damage, which were also demonstrated in mice with their ventral midbrain
microinjected with GSK4112, and then stimulated with LPS. Our results reveal that
enhanced REV-ERBalpha activity suppresses microglial activation through the NF
kappaB pathway in the central nervous system.
PMID- 29950612
TI - Nut consumption and the risk of oesophageal squamous cell carcinoma in the
Golestan Cohort Study.
AB - BACKGROUND: Nut consumption has been inversely associated with gastric cancer
incidence in US-based studies, but not with oesophageal cancer. However, there is
aetiologic heterogeneity, among oesophageal squamous cell carcinoma (ESCC) cases
in low-risk vs. high-risk populations. The objective of this study was to
evaluate the association between nut consumption and risk of ESCC in a high-risk
population. METHODS: The Golestan Cohort Study enroled 50,045 participants in
Northeastern Iran, between 2004 and 2008. Intake of peanuts, walnuts and mixed
nuts (including seeds) were assessed using a validated food frequency
questionnaire at baseline. Cox proportional hazard models were used to estimate
hazard ratios (HR) and 95% confidence intervals for subsequent ESCC adjusted for
potential confounders. Non-consumers of nuts were used as the reference category
and the consumers were categorised into tertiles. RESULTS: We accrued 280
incident ESCC cases during 337,983 person-years of follow up. Individuals in the
highest tertiles of total nut consumption, and mixed nut consumption were
significantly associated with lower risk of developing ESCC compared to non
consumers (HR = 0.60, 95% CI = 0.39-0.93, p-trend = 0.02, and HR = 0.52, 95% CI =
0.32-0.84, p trend = 0.002, respectively). CONCLUSIONS: We found a statistically
significant inverse association between total nut consumption and the risk of
ESCC in this high-risk population.
PMID- 29950616
TI - Veratridine modifies the gating of human voltage-gated sodium channel Nav1.7.
AB - Veratridine is a lipid-soluble neurotoxin derived from plants in the family
Liliaceae. It has been broadly investigated for its action as a sodium channel
agonist. However, the effects of veratridine on subtypes of sodium channels,
especially Nav1.7, remain to be studied. Here, we investigated the effects of
veratridine on human Nav1.7 ectopically expressed in HEK293A cells and recorded
Nav1.7 currents from the cells using whole-cell patch clamp technique. We found
that veratridine exerted a dose-dependent inhibitory effect on the peak current
of Nav1.7, with the half-maximal inhibition concentration (IC50) of 18.39 uM.
Meanwhile, veratridine also elicited tail current (linearly) and sustained
current [half-maximal concentration (EC50): 9.53 uM], also in a dose-dependent
manner. Veratridine (75 uM) shifted the half-maximal activation voltage of the
Nav1.7 activation curve in the hyperpolarized direction, from -21.64 +/- 0.75 mV
to -28.14 +/- 0.66 mV, and shifted the half-inactivation voltage of the steady
state inactivation curve from -59.39 +/- 0.39 mV to -73.78 +/- 0.5 mV. An
increased frequency of stimulation decreased the peak and tail currents of Nav1.7
for each pulse along with pulse number, and increased the accumulated tail
current at the end of train stimulation. These findings reveal the different
modulatory effects of veratridine on the Nav1.7 peak current and tail current.
PMID- 29950617
TI - Effects of SLCO1B1 and GATM gene variants on rosuvastatin-induced myopathy are
unrelated to high plasma exposure of rosuvastatin and its metabolites.
AB - Myotoxicity is a significant factor contributing to the poor adherence and
reduced effectiveness in the treatment of statins. Genetic variations and high
drug plasma exposure are considered as critique causes for statin-induced
myopathy (SIM). This study aims to explore the sequential influences of
rosuvastatin (RST) pharmacokinetic and myopathy-related single-nucleotide
polymorphisms (SNPs) on the plasma exposure to RST and its metabolites:
rosuvastatin lactone (RSTL) and N-desmethyl rosuvastatin (DM-RST), and further on
RST-induced myopathy. A total of 758 Chinese patients with coronary artery
disease were enrolled and followed up SIM incidents for 2 years. The plasma
concentrations of RST and its metabolites were determined through a validated
ultra-performance liquid chromatography mass spectrometry method. Nine SNPs in
six genes were genotyped by using the Sequenom MassArray iPlex platform. Results
revealed that ABCG2 rs2231142 variations were highly associated with the plasma
concentrations of RST, RSTL, and DM-RST (Padj < 0.01, FDR < 0.05). CYP2C9
rs1057910 significantly affected the DM-RST concentration (Padj < 0.01, FDR <
0.05). SLCO1B1 rs4149056 variant allele was significantly associated with high
SIM risk (OR: 1.741, 95% CI: 1.180-2.568, P = 0.0052, FDR = 0.0468). Glycine
amidinotransferase (GATM) rs9806699 was marginally associated with SIM incidents
(OR: 0.617, 95% CI: 0.406-0.939, P = 0.0240, FDR = 0.0960). The plasma
concentrations of RST and its metabolites were not significantly different
between the SIM (n = 51) and control groups (n = 707) (all P > 0.05). In
conclusion, SLCO1B1 and GATM genetic variants are potential biomarkers for
predicting RST-induced myopathy, and their effects on SIM are unrelated to the
high plasma exposure of RST and its metabolites.
PMID- 29950618
TI - The Effect of Arctic Dust on the Retrieval of Satellite Derived Sea and Ice
Surface Temperatures.
AB - Large quantities of dust are transported annually to the Arctic, primarily from
Asian deserts. The influx of dust into the polar environment changes the
radiative properties of clouds while the deposition of dust onto ice and snow
decreases the surface albedo. Atmospheric and surface dust may be identified with
space borne radiometers by comparing infrared energy in the 11 MUm and 12 MUm
regime. Between 2007 and 2017 satellite infrared data revealed persistent low
level dust clouds in the vicinity of Amundsen Gulf in the Western Canadian Arctic
during the melting season. Evidence suggests that the subsequent deposition of
atmospheric dust in the region affected the surface emissivity in the thermal
infrared regime. As a result, satellite derived sea and ice surface temperature
algorithms were rendered inaccurate in these areas. Moreover, the ubiquitous
nature of dust in the region may play a role in the rapidly vanishing cryosphere.
PMID- 29950619
TI - From the betweenness centrality in street networks to structural invariants in
random planar graphs.
AB - The betweenness centrality, a path-based global measure of flow, is a static
predictor of congestion and load on networks. Here we demonstrate that its
statistical distribution is invariant for planar networks, that are used to model
many infrastructural and biological systems. Empirical analysis of street
networks from 97 cities worldwide, along with simulations of random planar graph
models, indicates the observed invariance to be a consequence of a bimodal regime
consisting of an underlying tree structure for high betweenness nodes, and a low
betweenness regime corresponding to loops providing local path alternatives.
Furthermore, the high betweenness nodes display a non-trivial spatial clustering
with increasing spatial correlation as a function of the edge-density. Our
results suggest that the spatial distribution of betweenness is a more accurate
discriminator than its statistics for comparing static congestion patterns and
its evolution across cities as demonstrated by analyzing 200 years of street data
for Paris.
PMID- 29950620
TI - Evidence for extremely rapid magma ocean crystallization and crust formation on
Mars.
AB - The formation of a primordial crust is a critical step in the evolution of
terrestrial planets but the timing of this process is poorly understood. The
mineral zircon is a powerful tool for constraining crust formation because it can
be accurately dated with the uranium-to-lead (U-Pb) isotopic decay system and is
resistant to subsequent alteration. Moreover, given the high concentration of
hafnium in zircon, the lutetium-to-hafnium (176Lu-176Hf) isotopic decay system
can be used to determine the nature and formation timescale of its source
reservoir1-3. Ancient igneous zircons with crystallization ages of around 4,430
million years (Myr) have been reported in Martian meteorites that are believed to
represent regolith breccias from the southern highlands of Mars4,5. These zircons
are present in evolved lithologies interpreted to reflect re-melted primary
Martian crust 4 , thereby potentially providing insight into early crustal
evolution on Mars. Here, we report concomitant high-precision U-Pb ages and Hf
isotope compositions of ancient zircons from the NWA 7034 Martian regolith
breccia. Seven zircons with mostly concordant U-Pb ages define 207Pb/206Pb dates
ranging from 4,476.3 +/- 0.9 Myr ago to 4,429.7 +/- 1.0 Myr ago, including the
oldest directly dated material from Mars. All zircons record unradiogenic initial
Hf-isotope compositions inherited from an enriched, andesitic-like crust
extracted from a primitive mantle no later than 4,547 Myr ago. Thus, a primordial
crust existed on Mars by this time and survived for around 100 Myr before it was
reworked, possibly by impacts4,5, to produce magmas from which the zircons
crystallized. Given that formation of a stable primordial crust is the end
product of planetary differentiation, our data require that the accretion, core
formation and magma ocean crystallization on Mars were completed less than 20 Myr
after the formation of the Solar System. These timescales support models that
suggest extremely rapid magma ocean crystallization leading to a gravitationally
unstable stratified mantle, which subsequently overturns, resulting in
decompression melting of rising cumulates and production of a primordial basaltic
to andesitic crust6,7.
PMID- 29950621
TI - Triggers of tree mortality under drought.
AB - Severe droughts have caused widespread tree mortality across many forest biomes
with profound effects on the function of ecosystems and carbon balance. Climate
change is expected to intensify regional-scale droughts, focusing attention on
the physiological basis of drought-induced tree mortality. Recent work has shown
that catastrophic failure of the plant hydraulic system is a principal mechanism
involved in extensive crown death and tree mortality during drought, but the
multi-dimensional response of trees to desiccation is complex. Here we focus on
the current understanding of tree hydraulic performance under drought, the
identification of physiological thresholds that precipitate mortality and the
mechanisms of recovery after drought. Building on this, we discuss the potential
application of hydraulic thresholds to process-based models that predict
mortality.
PMID- 29950622
TI - A standing molecule as a single-electron field emitter.
AB - Scanning probe microscopy makes it possible to image and spectroscopically
characterize nanoscale objects, and to manipulate1-3 and excite4-8 them; even
time-resolved experiments are now routinely achieved9,10. This combination of
capabilities has enabled proof-of-principle demonstrations of nanoscale devices,
including logic operations based on molecular cascades 11 , a single-atom
transistor 12 , a single-atom magnetic memory cell 13 and a kilobyte atomic
memory 14 . However, a key challenge is fabricating device structures that can
overcome their attraction to the underlying surface and thus protrude from the
two-dimensional flatlands of the surface. Here we demonstrate the fabrication of
such a structure: we use the tip of a scanning probe microscope to lift a large
planar aromatic molecule (3,4,9,10-perylenetetracarboxylic-dianhydride) into an
upright, standing geometry on a pedestal of two metal (silver) adatoms. This
atypical and surprisingly stable upright orientation of the single molecule,
which under all known circumstances adsorbs flat on metals15,16, enables the
system to function as a coherent single-electron field emitter. We anticipate
that other metastable adsorbate configurations might also be accessible, thereby
opening up the third dimension for the design of functional nanostructures on
surfaces.
PMID- 29950624
TI - Flying couplers above spinning resonators generate irreversible refraction.
AB - Creating optical components that allow light to propagate in only one direction
that is, that allow non-reciprocal propagation or 'isolation' of light-is
important for a range of applications. Non-reciprocal propagation of sound can be
achieved simply by using mechanical components that spin1,2. Spinning also
affects de Broglie waves 3 , so a similar idea could be applied in optics.
However, the extreme rotation rates that would be required, owing to light
travelling much faster than sound, lead to unwanted wobbling. This wobbling makes
it difficult to maintain the separation between the spinning devices and the
couplers to within tolerance ranges of several nanometres, which is essential for
critical coupling4,5. Consequently, previous applications of optical6-17 and
optomechanical10,17-20 isolation have used alternative methods. In hard-drive
technology, the magnetic read heads of a hard-disk drive fly aerodynamically
above the rapidly rotating disk with nanometre precision, separated by a thin
film of air with near-zero drag that acts as a lubrication layer 21 . Inspired by
this, here we report the fabrication of photonic couplers (tapered fibres that
couple light into the resonators) that similarly fly above spherical resonators
with a separation of only a few nanometres. The resonators spin fast enough to
split their counter-circulating optical modes, making the fibre coupler
transparent from one side while simultaneously opaque from the other-that is,
generating irreversible transmission. Our setup provides 99.6 per cent isolation
of light in standard telecommunication fibres, of the type used for fibre-based
quantum interconnects 22 . Unlike flat geometries, such as between a magnetic
head and spinning disk, the saddle-like, convex geometry of the fibre and sphere
in our setup makes it relatively easy to bring the two closer together, which
could enable surface-science studies at nanometre-scale separations.
PMID- 29950623
TI - Macromolecular organic compounds from the depths of Enceladus.
AB - Saturn's moon Enceladus harbours a global water ocean 1 , which lies under an ice
crust and above a rocky core 2 . Through warm cracks in the crust 3 a cryo
volcanic plume ejects ice grains and vapour into space4-7 that contain materials
originating from the ocean8,9. Hydrothermal activity is suspected to occur deep
inside the porous core10-12, powered by tidal dissipation 13 . So far, only
simple organic compounds with molecular masses mostly below 50 atomic mass units
have been observed in plume material6,14,15. Here we report observations of
emitted ice grains containing concentrated and complex macromolecular organic
material with molecular masses above 200 atomic mass units. The data constrain
the macromolecular structure of organics detected in the ice grains and suggest
the presence of a thin organic-rich film on top of the oceanic water table, where
organic nucleation cores generated by the bursting of bubbles allow the probing
of Enceladus' organic inventory in enhanced concentrations.
PMID- 29950625
TI - Citations must default to the online publication date.
PMID- 29950626
TI - One wolf shot in Denmark is too many.
PMID- 29950628
TI - A call for IPBES to fix policies that harm scavengers.
PMID- 29950627
TI - AI could threaten pharmaceutical patents.
PMID- 29950629
TI - Nature editor bids farewell.
PMID- 29950630
TI - Young scientists aim to prioritize patients.
PMID- 29950631
TI - Science stars of East Asia.
PMID- 29950632
TI - South Korean science needs restructuring.
PMID- 29950633
TI - Mysteries of Indian monsoon probed in Bay of Bengal.
PMID- 29950635
TI - How Malaysian science can improve lives as well as the economy.
PMID- 29950636
TI - How to build a lab in East Asia's science hot spots.
PMID- 29950637
TI - Science in East Asia - by the numbers.
PMID- 29950639
TI - Five hubs of Asian science.
PMID- 29950638
TI - Asteroid defence, marijuana drug and Koko the gorilla.
PMID- 29950640
TI - A guide to the Nature Index.
PMID- 29950641
TI - Big data goes green.
PMID- 29950642
TI - Paving the way to an urban future.
PMID- 29950643
TI - Gravitational pull.
PMID- 29950645
TI - The search for solutions.
PMID- 29950644
TI - Pooled resources.
PMID- 29950646
TI - In the line of fire.
PMID- 29950647
TI - Zoom in on the big picture.
PMID- 29950649
TI - Making waves.
PMID- 29950648
TI - Casting a net for knowledge.
PMID- 29950650
TI - Core values.
PMID- 29950651
TI - Quiescence status of glioblastoma stem-like cells involves remodelling of Ca2+
signalling and mitochondrial shape.
AB - Quiescence is a reversible cell-cycle arrest which allows cancer stem-like cells
to evade killing following therapies. Here, we show that proliferating
glioblastoma stem-like cells (GSLCs) can be induced and maintained in a quiescent
state by lowering the extracellular pH. Through RNAseq analysis we identified
Ca2+ signalling genes differentially expressed between proliferating and
quiescent GSLCs. Using the bioluminescent Ca2+ reporter EGFP-aequorin we observed
that the changes in Ca2+ homeostasis occurring during the switch from
proliferation to quiescence are controlled through store-operated channels (SOC)
since inhibition of SOC drives proliferating GSLCs to quiescence. We showed that
this switch is characterized by an increased capacity of GSLCs' mitochondria to
capture Ca2+ and by a dramatic and reversible change of mitochondrial morphology
from a tubular to a donut shape. Our data suggest that the remodelling of the
Ca2+ homeostasis and the reshaping of mitochondria might favours quiescent GSLCs'
survival and their aggressiveness in glioblastoma.
PMID- 29950652
TI - Southern Hemisphere westerlies as a driver of the early deglacial atmospheric CO2
rise.
AB - The early part of the last deglaciation is characterised by a ~40 ppm atmospheric
CO2 rise occurring in two abrupt phases. The underlying mechanisms driving these
increases remain a subject of intense debate. Here, we successfully reproduce
changes in CO2, delta13C and Delta14C as recorded by paleo-records during
Heinrich stadial 1 (HS1). We show that HS1 CO2 increase can be explained by
enhanced Southern Ocean upwelling of carbon-rich Pacific deep and intermediate
waters, resulting from intensified Southern Ocean convection and Southern
Hemisphere (SH) westerlies. While enhanced Antarctic Bottom Water formation leads
to a millennial CO2 outgassing, intensified SH westerlies induce a multi-decadal
atmospheric CO2 rise. A strengthening of SH westerlies in a global eddy
permitting ocean model further supports a multi-decadal CO2 outgassing from the
Southern Ocean. Our results highlight the crucial role of SH westerlies in the
global climate and carbon cycle system with important implications for future
climate projections.
PMID- 29950653
TI - Strong activation effect on a ru-co-c thin film catalyst for the hydrolysis of
sodium borohydride.
AB - In this work, we prepared a series of Ni foam supported Ru-Co, Ru-Co-B and Ru-Co
C catalysts in the form of columnar thin films by magnetron sputtering for the
hydrolysis of sodium borohydride. We studied the activity and durability upon
cycling. We found a strong activation effect for the Ru-Co-C sample which was the
highest ever reported. This catalyst reached in the second cycle an activity 5
times higher than the initial (maximum activity 9310 ml.min-1.gCoRu-1 at 25
degrees C). Catalytic studies and characterization of the fresh and used samples
permitted to attribute the strong activation effect to the following factors: (i)
small column width and amorphous character (ii) the presence of Ru and (iii) dry
state before each cycle. The presence of boron in the initial composition is
detrimental to the durability. Our studies point out to the idea that after the
first cycle the activity is controlled by surface Ru, which is the most active of
the two metals. Apart from the activation effect, we found that catalysts
deactivated in further cycles. We ascribed this effect to the loss of cobalt in
the form of hydroxides, showing that deactivation was controlled by the chemistry
of Co, the major surface metal component of the alloy. Alloying with Ru is
beneficial for the activity but not for the durability, and this should be
improved.
PMID- 29950654
TI - Confined photo-release of nitric oxide with simultaneous two-photon fluorescence
tracking in a cellular system.
AB - Nitric oxide (NO) is a key signaling molecule in biological systems. New tools
are required to therapeutically modulate NO levels with confined precision. This
study explores the photoactivatable properties of an NO releasing compound (CPA),
based on cupferron O-alkylated with an anthracene derivative. Upon light
stimulation, CPA uncages two species: cupferron, which liberates NO, and an
anthrylmethyl carbocation, which evolves into a fluorescent reporter. Proof-of
principle is demonstrated using one- and two-photon excitation (1PE and 2PE) in a
cellular system (A431 cells). It was found that 1PE induces cell toxicity, while
2PE does not. Since 1PE using UV light is more likely to generate cellular
photodamage, the cell toxicity observed using 1PE is most likely a combinatory
effect of NO release and other UV-induced damage, which should be subject to
further investigation. On the other hand, absence of phototoxicity using 2PE
suggests that NO alone is not cytotoxic. This leads to the conclusion that the
concept of 2PE photorelease of NO from CPA enable opportunities for biological
studies of NO signaling with confined precision of NO release with minimal
cytotoxicity.
PMID- 29950655
TI - C-NHEJ without indels is robust and requires synergistic function of distinct XLF
domains.
AB - To investigate the fidelity of canonical non-homologous end joining (C-NHEJ), we
developed an assay to detect EJ between distal ends of two Cas9-induced
chromosomal breaks that are joined without causing insertion/deletion mutations
(indels). Here we find that such EJ requires several core C-NHEJ factors,
including XLF. Using variants of this assay, we find that C-NHEJ is required for
EJ events that use 1-2, but not >=3, nucleotides of terminal microhomology. We
also investigated XLF residues required for EJ without indels, finding that one
of two binding domains is essential (L115 or C-terminal lysines that bind XRCC4
and KU/DNA, respectively), and that disruption of one of these domains sensitizes
XLF to mutations that affect its dimer interface, which we examined with
molecular dynamic simulations. Thus, C-NHEJ, including synergistic function of
distinct XLF domains, is required for EJ of chromosomal breaks without indels.
PMID- 29950657
TI - Growth of a common planktonic diatom quantified using solid medium culturing.
AB - The ability to grow on solid culture medium is a pre-requisite for a successful
microbial genetic model organism. Skeletonema marinoi, a bloom-forming,
planktonic marine microalga, is widely used in ecological, evolutionary and
population genetics studies. We have tested and confirmed the ability of this
common organism to grow on solid culture medium (agar) under experimentally
manipulated conditions. We established a protocol for quantifying growth
characteristics - length of lag phase, growth rate, maximum biomass yield - on
agar medium. The procedure was tested under experimental treatments and the
resulting growth changes correlated with those observed in standard liquid
culture. The ability to grow on solid medium broadens the use of S. marinoi as a
molecular model, where agar is routinely used for various purposes (growth,
selection, storage); and the possibility to quantify colony growth opens the way
for high throughput, automated, or semi-automated phenotyping solutions.
PMID- 29950656
TI - Fungal endophytes from arid areas of Andalusia: high potential sources for
antifungal and antitumoral agents.
AB - Native plant communities from arid areas present distinctive characteristics to
survive in extreme conditions. The large number of poorly studied endemic plants
represents a unique potential source for the discovery of novel fungal symbionts
as well as host-specific endophytes not yet described. The addition of adsorptive
polymeric resins in fungal fermentations has been seen to promote the production
of new secondary metabolites and is a tool used consistently to generate new
compounds with potential biological activities. A total of 349 fungal strains
isolated from 63 selected plant species from arid ecosystems located in the
southeast of the Iberian Peninsula, were characterized morphologically as well as
based on their ITS/28S ribosomal gene sequences. The fungal community isolated
was distributed among 19 orders including Basidiomycetes and Ascomycetes, being
Pleosporales the most abundant order. In total, 107 different genera were
identified being Neocamarosporium the genus most frequently isolated from these
plants, followed by Preussia and Alternaria. Strains were grown in four different
media in presence and absence of selected resins to promote chemical diversity
generation of new secondary metabolites. Fermentation extracts were evaluated,
looking for new antifungal activities against plant and human fungal pathogens,
as well as, cytotoxic activities against the human liver cancer cell line HepG2.
From the 349 isolates tested, 126 (36%) exhibited significant bioactivities
including 58 strains with exclusive antifungal properties and 33 strains with
exclusive activity against the HepG2 hepatocellular carcinoma cell line. After
LCMS analysis, 68 known bioactive secondary metabolites could be identified as
produced by 96 strains, and 12 likely unknown compounds were found in a subset of
14 fungal endophytes. The chemical profiles of the differential expression of
induced activities were compared. As proof of concept, ten active secondary
metabolites only produced in the presence of resins were purified and identified.
The structures of three of these compounds were new and herein are elucidated.
PMID- 29950658
TI - Extremely strong polarization of an active asteroid (3200) Phaethon.
AB - The near-Earth asteroid (3200) Phaethon is the parent body of the Geminid meteor
stream. Phaethon is also an active asteroid with a very blue spectrum. We
conducted polarimetric observations of this asteroid over a wide range of solar
phase angles alpha during its close approach to the Earth in autumn 2016. Our
observation revealed that Phaethon exhibits extremely large linear polarization:
P = 50.0 +/- 1.1% at alpha = 106.5 degrees , and its maximum is even larger. The
strong polarization implies that Phaethon's geometric albedo is lower than the
current estimate obtained through radiometric observation. This possibility stems
from the potential uncertainty in Phaethon's absolute magnitude. An alternative
possibility is that relatively large grains (~300 MUm in diameter, presumably due
to extensive heating near its perihelion) dominate this asteroid's surface. In
addition, the asteroid's surface porosity, if it is substantially large, can also
be an effective cause of this polarization.
PMID- 29950659
TI - Comparative analysis of xenobiotic metabolising N-acetyltransferases from ten non
human primates as in vitro models of human homologues.
AB - Xenobiotic metabolising N-acetyltransferases (NATs) perform biotransformation of
drugs and carcinogens. Human NAT1 is associated with endogenous metabolic
pathways of cells and is a candidate drug target for cancer. Human NAT2 is a well
characterised polymorphic xenobiotic metabolising enzyme, modulating
susceptibility to drug-induced toxicity. Human NATs are difficult to express to
high purification yields, complicating large-scale production for high-throughput
screens or use in sophisticated enzymology assays and crystallography. We
undertake comparative functional investigation of the NAT homologues of ten non
human primates, to characterise their properties and evaluate their suitability
as models of human NATs. Considering the amount of generated recombinant protein,
the enzymatic activity and thermal stability, the NAT homologues of non-human
primates are demonstrated to be a much more effective resource for in vitro
studies compared with human NATs. Certain NAT homologues are proposed as better
models, such as the NAT1 of macaques Macaca mulatta and M. sylvanus, the NAT2 of
Erythrocebus patas, and both NAT proteins of the gibbon Nomascus gabriellae which
show highest homology to human NATs. This comparative investigation will
facilitate in vitro screens towards discovery and optimisation of candidate
pharmaceutical compounds for human NAT isoenzymes, while enabling better
understanding of NAT function and evolution in primates.
PMID- 29950660
TI - Amorphous Carbon Dots and their Remarkable Ability to Detect 2,4,6
Trinitrophenol.
AB - Apparently mundane, amorphous nanostructures of carbon have optical properties
which are as exotic as their crystalline counterparts. In this work we
demonstrate a simple and inexpensive mechano-chemical method to prepare bulk
quantities of self-passivated, amorphous carbon dots. Like the graphene quantum
dots, the water soluble, amorphous carbon dots too, exhibit excitation-dependent
photoluminescence with very high quantum yield (~40%). The origin and nature of
luminescence in these high entropy nanostructures are well understood in terms of
the abundant surface traps. The photoluminescence property of these carbon dots
is exploited to detect trace amounts of the nitro-aromatic explosive - 2,4,6
trinitrophenol (TNP). The benign nanostructures can selectively detect TNP over a
wide range of concentrations (0.5 to 200 uM) simply by visual inspection, with a
detection limit of 0.2 uM, and consequently outperform nearly all reported TNP
sensor materials.
PMID- 29950661
TI - Ceratosaur palaeobiology: new insights on evolution and ecology of the southern
rulers.
AB - Ceratosaur theropods ruled the Southern Hemisphere until the end of the Late
Cretaceous. However, their origin was earlier, during the Early Jurassic, a fact
which allowed the group to reach great morphological diversity. The body plans of
the two main branches (Noasauridae and new name Etrigansauria: Ceratosauridae +
Abelisauridae) are quite different; nevertheless, they are sister taxa.
Abelisaurids have lost the ability to grasp in the most derived taxa, but the
reduced forelimb might have had some display function. The ontogenetic changes
are well known in Limusaurus which lost all their teeth and probably changed the
dietary preference at maturity. The results presented here suggest that
abelisaurids had different soft tissues on the skull. These tissues might have
been associated with evolution of a strong cervicocephalic complex and should
have allowed derived taxa (e.g. Majungasaurus and Carnotaurus) to have low
displacement headbutting matches. The ability to live in different semi-arid
environment plus high morphological disparity allowed the ceratosaurs to become
an evolutionary success.
PMID- 29950662
TI - Development and Validation of Nomogram to Predict Acute Kidney Injury in Patients
with Acute Myocardial Infarction Treated Invasively.
AB - To identify patients who are likely to develop contrast-induced acute kidney
injury (CI-AKI) in patients with acute myocardial infarction (AMI), a nomogram
was developed in AMI patients. Totally 920 patients with AMI were enrolled in our
study. The discrimination and calibration of the model were validated. External
validations were also carried out in a cohort of 386 AMI patients. Our results
showed in the 920 eligible AMI patients, 114 patients (21.3%) developed CI-AKI in
the derivation group (n = 534), while in the validation set (n = 386), 50
patients (13%) developed CI-AKI. CI-AKI model included the following six
predictors: hemoglobin, contrast volume >100 ml, hypotension before procedure,
eGFR, log BNP, and age. The area under the curve (AUC) was 0.775 (95% confidence
interval [CI]: 0.732-0.819) in the derivation group and 0.715 (95% CI: 0.631
0.799) in the validation group. The Hosmer-Lemeshow test has a p value of 0.557,
which confirms the model's goodness of fit. The AUC of the Mehran risk score was
0.556 (95% CI: 0.498-0.615) in the derivation group. The validated nomogram
provided a useful predictive value for CI-AKI in patients with AMI.
PMID- 29950663
TI - Publisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl
hydroxylation of TRAFAC GTPases.
AB - In the version of this article initially published, authors Sarah E. Wilkins,
Charlotte D. Eaton, Martine I. Abboud and Maximiliano J. Katz were incorrectly
included in the equal contributions footnote in the affiliations list. Footnote
number seven linking to the equal contributions statement should be present only
for Suzana Markolovic and Qinqin Zhuang, and the statement should read "These
authors contributed equally: Suzana Markolovic, Qinqin Zhuang." The error has
been corrected in the HTML and PDF versions of the article.
PMID- 29950664
TI - Clinical and genotypic CMV drug resistance in HSCT recipients: a single center
epidemiological and clinical data.
PMID- 29950667
TI - Modeling Alzheimer's disease brains in vitro.
PMID- 29950665
TI - Transcriptomics analysis reveals new insights in E171-induced molecular
alterations in a mouse model of colon cancer.
AB - Titanium dioxide as a food additive (E171) has been demonstrated to facilitate
growth of chemically induced colorectal tumours in vivo and induce transcriptomic
changes suggestive of an immune system impairment and cancer development. The
present study aimed to investigate the molecular mechanisms behind the tumour
stimulatory effects of E171 in combination with azoxymethane (AOM)/dextran sodium
sulphate (DSS) and compare these results to a recent study performed under the
same conditions with E171 only. BALB/c mice underwent exposure to 5 mg/kgbw/day
of E171 by gavage for 2, 7, 14, and 21 days. Whole genome mRNA microarray
analyses on the distal colon were performed. The results show that E171 induced a
downregulation of genes involved in the innate and adaptive immune system,
suggesting impairment of this system. In addition, over time, signalling genes
involved in colorectal cancer and other types of cancers were modulated. In
relation to cancer development, effects potentially associated with oxidative
stress were observed through modulation of genes related to antioxidant
production. E171 affected genes involved in biotransformation of xenobiotics
which can form reactive intermediates resulting in toxicological effects. These
transcriptomics data reflect the early biological responses induced by E171 which
precede tumour formation in an AOM/DSS mouse model.
PMID- 29950666
TI - Thermally-induced reversible structural isomerization in colloidal semiconductor
CdS magic-size clusters.
AB - Structural isomerism of colloidal semiconductor nanocrystals has been largely
unexplored. Here, we report one pair of structural isomers identified for
colloidal nanocrystals which exhibit thermally-induced reversible transformations
behaving like molecular isomerization. The two isomers are CdS magic-size
clusters with sharp absorption peaks at 311 and 322 nm. They have identical
cluster masses, but slightly different structures. Furthermore, their
interconversions follow first-order unimolecular reaction kinetics. We anticipate
that such isomeric kinetics are applicable to a variety of small-size functional
nanomaterials, and that the methodology developed for our kinetic study will be
helpful to investigate and exploit solid-solid transformations in other
semiconductor nanocrystals. The findings on structural isomerism should stimulate
attention toward advanced design and synthesis of functional nanomaterials
enabled by structural transformations.
PMID- 29950668
TI - Dorsal tegmental dopamine neurons gate associative learning of fear.
AB - Functional neuroanatomy of Pavlovian fear has identified neuronal circuits and
synapses associating conditioned stimuli with aversive events. Hebbian plasticity
within these networks requires additional reinforcement to store particularly
salient experiences into long-term memory. Here we have identified a circuit that
reciprocally connects the ventral periaqueductal gray and dorsal raphe region
with the central amygdala and that gates fear learning. We found that ventral
periaqueductal gray and dorsal raphe dopaminergic (vPdRD) neurons encode a
positive prediction error in response to unpredicted shocks and may reshape intra
amygdala connectivity via a dopamine-dependent form of long-term potentiation.
Negative feedback from the central amygdala to vPdRD neurons might limit
reinforcement to events that have not been predicted. These findings add a new
module to the midbrain dopaminergic circuit architecture underlying associative
reinforcement learning and identify vPdRD neurons as a critical component of
Pavlovian fear conditioning. We propose that dysregulation of vPdRD neuronal
activity may contribute to fear-related psychiatric disorders.
PMID- 29950669
TI - A 3D human triculture system modeling neurodegeneration and neuroinflammation in
Alzheimer's disease.
AB - Alzheimer's disease (AD) is characterized by beta-amyloid accumulation,
phosphorylated tau formation, hyperactivation of glial cells, and neuronal loss.
The mechanisms of AD pathogenesis, however, remain poorly understood, partially
due to the lack of relevant models that can comprehensively recapitulate
multistage intercellular interactions in human AD brains. Here we present a new
three-dimensional (3D) human AD triculture model using neurons, astrocytes, and
microglia in a 3D microfluidic platform. Our model provided key representative AD
features: beta-amyloid aggregation, phosphorylated tau accumulation, and
neuroinflammatory activity. In particular, the model mirrored microglial
recruitment, neurotoxic activities such as axonal cleavage, and NO release
damaging AD neurons and astrocytes. Our model will serve to facilitate the
development of more precise human brain models for basic mechanistic studies in
neural-glial interactions and drug discovery.
PMID- 29950670
TI - Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional
partitioning of localized transcripts.
AB - A localized transcriptome at the synapse facilitates synapse-, stimulus- and
transcript-specific local protein synthesis in response to neuronal activity.
While enzyme-mediated mRNA modifications are known to regulate cellular mRNA
turnover, the role of these modifications in regulating synaptic RNA has not been
studied. We established low-input m6A-sequencing of synaptosomal RNA to determine
the chemically modified local transcriptome in healthy adult mouse forebrains and
identified 4,469 selectively enriched m6A sites in 2,921 genes as the synaptic
m6A epitranscriptome (SME). The SME is functionally enriched in synthesis and
modulation of tripartite synapses and in pathways implicated in
neurodevelopmental and neuropsychiatric diseases. Interrupting m6A-mediated
regulation via knockdown of readers in hippocampal neurons altered expression of
SME member Apc, resulting in synaptic dysfunction including immature spine
morphology and dampened excitatory synaptic transmission concomitant with
decreased clusters of postsynaptic density-95 (PSD-95) and decreased surface
expression of AMPA receptor subunit GluA1. Our findings indicate that chemical
modifications of synaptic mRNAs critically contribute to synaptic function.
PMID- 29950671
TI - Flame retardant exposure assessment: findings from a behavioral intervention
study.
AB - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) have been largely replaced by
organophosphate flame retardants (OPFRs) and alternative brominated flame
retardants (Alt-BFRs) to meet flammability requirements. Humans are ubiquitously
exposed to some variety of flame retardants through contact with consumer
products directly or through household dust. OBJECTIVES: To evaluate the
effectiveness of house cleaning and hand washing practices to reduce exposure to
flame retardants, we measured concentrations in dermal hand wipes and urinary
metabolites before and after assignment to two consecutive interventions.
METHODS: We selected 32 mother and child dyads from an existing cohort. This
analysis focuses on mothers. Participants provided baseline measurements (urine,
hand wipes, and questionnaires) and were then assigned for 1 week to either a
house cleaning (including instruction on proper technique and cleaning supplies)
or hand washing (including instruction on proper technique and soaps)
intervention arm. For the second week, participants were assigned to the second
intervention in addition to their initial assignment, thus all subjects both
washed their hands and cleaned according to the intervention guidelines during
week 2. We collected measurements at the end of weeks 1 and 2. RESULTS: We found
reductions in urinary analytes after week 1 of house cleaning (BCIPHIPP and ip
DPHP), week 1 of hand washing (BCIPP, BCIPHIPP, and tbutyl-DPHP), and week 2 of
combined interventions (BCIPHIPP and tbutyl-DPHP), compare to baseline. We found
no significant decline in hand wipes in the entire sample but did find reductions
after week 1 of house cleaning (BDE 209), week 1 of hand washing (TCEP), and week
2 of combined interventions (TDCIPP and BDE 209) in women with exposure above the
median at baseline (verified through simulations). CONCLUSIONS: Exposure to
individual flame retardants was reduced by about half, in some cases, by 1 week
of increased hand washing, house cleaning to reduce dust, or combined activities.
PMID- 29950672
TI - Operando X-ray photoelectron spectroscopy of solid electrolyte interphase
formation and evolution in Li2S-P2S5 solid-state electrolytes.
AB - Solid-state electrolytes such as Li2S-P2S5 compounds are promising materials that
could enable Li metal anodes. However, many solid-state electrolytes are unstable
against metallic lithium, and little is known about the chemical evolution of
these interfaces during cycling, hindering the rational design of these
materials. In this work, operando X-ray photoelectron spectroscopy and real-time
in situ Auger electron spectroscopy mapping are developed to probe the formation
and evolution of the Li/Li2S-P2S5 solid-electrolyte interphase during
electrochemical cycling, and to measure individual overpotentials associated with
specific interphase constituents. Results for the Li/Li2S-P2S5 system reveal that
electrochemically driving Li+ to the surface leads to phase decomposition into
Li2S and Li3P. Additionally, oxygen contamination within the Li2S-P2S5 leads
initially to Li3PO4 phase segregation, and subsequently to Li2O formation. The
spatially non-uniform distribution of these phases, coupled with differences in
their ionic conductivities, have important implications for the overall
properties and performance of the solid-electrolyte interphase.
PMID- 29950673
TI - mTORC1 accelerates retinal development via the immunoproteasome.
AB - The numbers and types of cells constituting vertebrate neural tissues are
determined by cellular mechanisms that couple neurogenesis to the proliferation
of neural progenitor cells. Here we identified a role of mammalian target of
rapamycin complex 1 (mTORC1) in the development of neural tissue, showing that it
accelerates progenitor cell cycle progression and neurogenesis in mTORC1
hyperactive tuberous sclerosis complex 1 (Tsc1)-deficient mouse retina. We also
show that concomitant loss of immunoproteasome subunit Psmb9, which is induced by
Stat1 (signal transducer and activator of transcription factor 1), decelerates
cell cycle progression of Tsc1-deficient mouse retinal progenitor cells and
normalizes retinal developmental schedule. Collectively, our results establish a
developmental role for mTORC1, showing that it promotes neural development
through activation of protein turnover via a mechanism involving the
immunoproteasome.
PMID- 29950675
TI - Generation of hydroxyl radicals by Fe-polyphenol-activated CaO2 as a potential
treatment for soil-borne diseases.
AB - An Fe-polyphenol catalyst was recently developed using anhydrous iron (III)
chloride and coffee grounds as raw materials. The present study aims to test the
application of this Fe-polyphenol catalyst with two hydrogen peroxide (H2O2)
sources in soil as a new method for controlling the soil-borne disease caused by
Ralstonia solanacearum and to test the hypothesis that hydroxyl radicals are
involved in the catalytic process. Tomato cv. Momotaro was used as the test
species. The results showed that powdered CaO2 (16% W/W) is a more effective H2O2
source for controlling bacterial wilt disease than liquid H2O2 (35% W/W) when
applied with an Fe-polyphenol catalyst. An electron paramagnetic resonance spin
trapping method using a 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) assay and Fe
caffeic acid and Fe-chlorogenic acid complexes as models showed that these
organometallic complexes react with the H2O2 released by CaO2, producing hydroxyl
radicals in a manner that is consistent with the proposed catalytic process. The
application of Fe-polyphenol with powdered CaO2 to soil could be a new
environmentally friendly method for controlling soil-borne diseases.
PMID- 29950674
TI - Identification of genes associated with cortical malformation using a transposon
mediated somatic mutagenesis screen in mice.
AB - Mutations in genes involved in the production, migration, or differentiation of
cortical neurons often lead to malformations of cortical development (MCDs).
However, many genetic mutations involved in MCD pathogenesis remain unidentified.
Here we developed a genetic screening paradigm based on transposon-mediated
somatic mutagenesis by in utero electroporation and the inability of mutant
neuronal precursors to migrate to the cortex and identified 33 candidate MCD
genes. Consistent with the screen, several genes have already been implicated in
neural development and disorders. Functional disruption of the candidate genes by
RNAi or CRISPR/Cas9 causes altered neuronal distributions that resemble human
cortical dysplasia. To verify potential clinical relevance of these candidate
genes, we analyzed somatic mutations in brain tissue from patients with focal
cortical dysplasia and found that mutations are enriched in these candidate
genes. These results demonstrate that this approach is able to identify potential
mouse genes involved in cortical development and MCD pathogenesis.
PMID- 29950676
TI - Endospore forming bacteria may be associated with maintenance of surgically
induced remission in Crohn's disease.
AB - Crohn's disease (CD) patients who undergo ileocolonic resection (ICR) typically
have disease recurrence at the anastomosis which has been linked with a gut
dysbiosis. The aims of this study were to define the mucosa-associated microbiota
at the time of ICR and to determine if microbial community structure at the time
of surgery was predictive of future disease relapse. Ileal biopsies were obtained
at surgery and after 6 months from CD subjects undergoing ICR. Composition and
function of mucosal-associated microbiota was assessed by 16S rRNA sequencing and
PICRUSt analysis. Endoscopic recurrence was assessed using the Rutgeerts score.
Analysis of mucosal biopsies taken at the time of surgery showed that decreased
Clostridiales together with increased Enterobacteriales predicted disease
recurrence. An increase in the endospore-forming Lachnospiraceae from surgery to
6 months post-ICR was associated with remission. A ratio of 3:1 between anaerobic
endospore-forming bacterial families and aerobic families within the Firmicutes
phylum was predictive of maintenance of remission. Gut recolonization following
ICR is facilitated by microbes which are capable of either aerobic respiration or
endospore formation. The relative proportions of these species at the time of
surgery may be predictive of subsequent microbial community restoration and
disease recurrence.
PMID- 29950677
TI - A novel high-throughput method for kinetic characterisation of anaerobic
bioproduction strains, applied to Clostridium kluyveri.
AB - Hexanoic acid (HA), also called caproic acid, can be used as an antimicrobial
agent and as a precursor to various chemicals, such as fuels, solvents and
fragrances. HA can be produced from ethanol and acetate by the mesophilic
anaerobic bacterium Clostridium kluyveri, via two successive elongation steps
over butyrate. A high-throughput anaerobic growth curve technique was coupled to
a data analysis framework to assess growth kinetics for a range of substrate and
product concentrations. Using this method, growth rates and several kinetic
parameters were determined for C. kluyveri. A maximum growth rate (umax) of 0.24
+/- 0.01 h-1 was found, with a half-saturation index for acetic acid (KS,AA) of
3.8 +/- 0.9 mM. Inhibition by butyric acid occurred at of 124.7 +/- 5.7 mM
(KI,BA), while the final product, HA, linearly inhibited growth with complete
inhibition above 91.3 +/- 10.8 mM (KHA of 10.9*10-3 +/- 1.3*10-3 mM-1) at pH = 7,
indicating that the hexanoate anion also exerts toxicity. These parameters were
used to create a dynamic mass-balance model for bioproduction of HA. By coupling
data collection and analysis to this modelling framework, we have produced a
powerful tool to assess the kinetics of anaerobic micro-organisms, demonstrated
here with C. kluyveri, in order further explore the potential of micro-organisms
for chemicals production.
PMID- 29950678
TI - Discovery of ZrCoBi based half Heuslers with high thermoelectric conversion
efficiency.
AB - Thermoelectric materials are capable of converting waste heat into electricity.
The dimensionless figure-of-merit (ZT), as the critical measure for the
material's thermoelectric performance, plays a decisive role in the energy
conversion efficiency. Half-Heusler materials, as one of the most promising
candidates for thermoelectric power generation, have relatively low ZTs compared
to other material systems. Here we report the discovery of p-type ZrCoBi-based
half-Heuslers with a record-high ZT of ~1.42 at 973 K and a high thermoelectric
conversion efficiency of ~9% at the temperature difference of ~500 K. Such an
outstanding thermoelectric performance originates from its unique band structure
offering a high band degeneracy (Nv) of 10 in conjunction with a low thermal
conductivity benefiting from the low mean sound velocity (vm ~2800 m s-1). Our
work demonstrates that ZrCoBi-based half-Heuslers are promising candidates for
high-temperature thermoelectric power generation.
PMID- 29950679
TI - Biomarker discovery by integrated joint non-negative matrix factorization and
pathway signature analyses.
AB - Predictive biomarkers are important for selecting appropriate patients for
particular treatments. Comprehensive genomic, transcriptomic, and pharmacological
data provide clues for understanding relationships between biomarkers and drugs.
However, it is still difficult to mine biologically meaningful biomarkers from
multi-omics data. Here, we developed an approach for mining multi-omics cell line
data by integrating joint non-negative matrix factorization (JNMF) and pathway
signature analyses to identify candidate biomarkers. The JNMF detected known
associations between biomarkers and drugs such as BRAF mutation with PLX4720 and
HER2 amplification with lapatinib. Furthermore, we observed that tumours with
both BRAF mutation and MITF activation were more sensitive to BRAF inhibitors
compared to tumours with BRAF mutation without MITF activation. Therefore,
activation of the BRAF/MITF axis seems to be a more appropriate biomarker for
predicting the efficacy of a BRAF inhibitor than the conventional biomarker of
BRAF mutation alone. Our biomarker discovery scheme represents an integration of
JNMF multi-omics clustering and multi-layer interpretation based on pathway gene
signature analyses. This approach is also expected to be useful for establishing
drug development strategies, identifying pharmacodynamic biomarkers, in mode of
action analysis, as well as for mining drug response data in a clinical setting.
PMID- 29950680
TI - Direct visualization of current-induced spin accumulation in topological
insulators.
AB - Charge-to-spin conversion in various materials is the key for the fundamental
understanding of spin-orbitronics and efficient magnetization manipulation. Here
we report the direct spatial imaging of current-induced spin accumulation at the
channel edges of Bi2Se3 and BiSbTeSe2 topological insulators as well as Pt by a
scanning photovoltage microscope at room temperature. The spin polarization is
along the out-of-plane direction with opposite signs for the two channel edges.
The accumulated spin direction reverses sign upon changing the current direction
and the detected spin signal shows a linear dependence on the magnitude of
currents, indicating that our observed phenomena are current-induced effects. The
spin Hall angle of Bi2Se3, BiSbTeSe2, and Pt is determined to be 0.0085, 0.0616,
and 0.0085, respectively. Our results open up the possibility of optically
detecting the current-induced spin accumulations, and thus point towards a better
understanding of the interaction between spins and circularly polarized light.
PMID- 29950681
TI - Predicting the Enthalpy and Gibbs Energy of Sublimation by QSPR Modeling.
AB - The enthalpy and Gibbs energy of sublimation are predicted using quantitative
structure property relationship (QSPR) models. In this study, we compare several
approaches previously reported in the literature for predicting the enthalpy of
sublimation. These models, which were reproduced successfully, exhibit high
correlation coefficients, in the range 0.82 to 0.97. There are significantly
fewer examples of QSPR models currently described in the literature that predict
the Gibbs energy of sublimation; here we describe several models that build upon
the previous models for predicting the enthalpy of sublimation. The most robust
and predictive model constructed using multiple linear regression, with the
fewest number of descriptors for estimating this property, was obtained with an
R2 of the training set of 0.71, an R2 of the test set of 0.62, and a standard
deviation of 9.1 kJ mol-1. This model could be improved by training using a
neural network, yielding an R2 of the training and test sets of 0.80 and 0.63,
respectively, and a standard deviation of 8.9 kJ mol-1.
PMID- 29950682
TI - Age-related shift in LTD is dependent on neuronal adenosine A2A receptors
interplay with mGluR5 and NMDA receptors.
AB - Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it
drives the cognitive decline. An association between a polymorphism of the
adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD
patients was recently described. In this study, we explore the synaptic function
of A2AR in age-related conditions. We report, for the first time, a significant
overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated
in AD patients. A similar profile of A2AR overexpression in rats was sufficient
to drive age-like memory impairments in young animals and to uncover a
hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor
gating, dependent on mGluR5 and linked to enhanced Ca2+ influx. We confirmed the
same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD,
which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might
prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD
without disrupting their constitutive activity.
PMID- 29950683
TI - Reduced secretion of parathyroid hormone and hypocalcemia in systemic
heterozygous ATP2B1-null hypertensive mice.
AB - The ATP2B1 gene is associated with hypertension. We previously reported that
systemic heterozygous ATP2B1-null (ATP2B1+/-) mice exhibited hypertension due to
impaired endothelial nitric oxide synthase (eNOS) activity and decreased nitric
oxide (NO) production. The ATP2B1 gene encodes plasma membrane calcium ATPase 1
(PMCA1), which has been thought to regulate only intracellular Ca2+
concentration. However, recently, it has been suggested that ATP2B1 works not
only at cellular levels, but also throughout the entire body, including in the
calcium metabolism, using small intestine-specific ATP2B1 knockout mice. To
clarify the roles of ATP2B1 in the entire body and the effects of ATP2B1 on blood
pressure, we examined the alterations of calcium related factors in ATP2B1+/-
mice. ATP2B1+/- mice exhibited hypocalcemia. The expression of ATP2B1 in the
kidney and small intestine decreased, and hypercalciuria was confirmed in
ATP2B1+/- mice. The intact-PTH levels were lower, and bone mineral density was
increased in these mice. These results suggest that hypocalcemia is mainly a
result of inhibited bone resorption without compensation by PTH secretion in the
case of ATP2B1 knockout. Moreover, NO production may be affected by reduced PTH
secretion, which may cause the increase in vascular contractility in these mice.
The ATP2B1 gene is important for not only intra-cellular calcium regulation but
also for calcium homeostasis and blood pressure control.
PMID- 29950684
TI - SETD3 negatively regulates VEGF expression during hypoxic pulmonary hypertension
in rats.
AB - Angiogenesis and activation of vascular endothelial growth factor (VEGF)
signaling are tightly regulated under the condition of hypoxic pulmonary
hypertension (HPH); therefore, deciphering the regulatory mechanisms associated
with VEGF is important. SET domain-containing 3 (SETD3) and VEGF expression in
lung tissue during hypoxia exposure and lentivirus. SETD3 treatments were
detected by real-time PCR and Western blot analysis. Remodeling of pulmonary
vasculature and hypertrophy of the RV were evaluated. The effects of SETD3 over
expression on the interaction between SETD3 and forkhead box protein M1 (FoxM1)
at the VEGF promoter and downstream of the VEGF signal pathway during chronic
hypoxia were detected. SETD3 lentiviral vector treatment not only inhibited the
increase in VEGF expression but also significantly relieved pulmonary vasculature
remodeling and hypertrophy of the RV during HPH. The functional interplay between
SETD3 and FoxM1 on chromatin may negatively regulate VEGF expression under HPH
through the VEGF receptor-extracellular signal-regulated kinase-hypoxia-induced
factor-1 signal pathway. SETD3-mediated transcriptional modification of VEGF may
be a potential target to inhibit the development of HPH.
PMID- 29950685
TI - Keratinocyte differentiation induces APOBEC3A, 3B, and mitochondrial DNA
hypermutation.
AB - Mitochondrial DNA (mtDNA) mutations are found in many types of cancers and
suspected to be involved in carcinogenesis, although the mechanism has not been
elucidated. In this study, we report that consecutive C-to-T mutations
(hypermutations), a unique feature of mutations induced by APOBECs, are found in
mtDNA from cervical dysplasia and oropharyngeal cancers. In vitro, we found that
APOBEC3A (A3A) and 3B (A3B) expression, as well as mtDNA hypermutation, were
induced in a cervical dysplastic cell line W12 when cultured in a differentiating
condition. The ectopic expression of A3A or A3B was sufficient to hypermutate
mtDNA. Fractionation of W12 cell lysates and immunocytochemical analysis revealed
that A3A and A3B could be contained in mitochondrion. These results suggest that
mtDNA hypermutation is induced upon keratinocyte differentiation, and shed light
on its molecular mechanism, which involves A3s. The possible involvement of mtDNA
hypermutations in carcinogenesis is also discussed.
PMID- 29950686
TI - Uncovering hidden brain state dynamics that regulate performance and decision
making during cognition.
AB - Human cognition is influenced not only by external task demands but also latent
mental processes and brain states that change over time. Here, we use novel
Bayesian switching dynamical systems algorithm to identify hidden brain states
and determine that these states are only weakly aligned with external task
conditions. We compute state transition probabilities and demonstrate how dynamic
transitions between hidden states allow flexible reconfiguration of functional
brain circuits. Crucially, we identify latent transient brain states and dynamic
functional circuits that are optimal for cognition and show that failure to
engage these states in a timely manner is associated with poorer task performance
and weaker decision-making dynamics. We replicate findings in a large sample (N =
122) and reveal a robust link between cognition and flexible latent brain state
dynamics. Our study demonstrates the power of switching dynamical systems models
for investigating hidden dynamic brain states and functional interactions
underlying human cognition.
PMID- 29950687
TI - Dissecting ribosomal particles throughout the kingdoms of life using advanced
hybrid mass spectrometry methods.
AB - Biomolecular mass spectrometry has matured strongly over the past decades and has
now reached a stage where it can provide deep insights into the structure and
composition of large cellular assemblies. Here, we describe a three-tiered hybrid
mass spectrometry approach that enables the dissection of macromolecular
complexes in order to complement structural studies. To demonstrate the
capabilities of the approach, we investigate ribosomes, large ribonucleoprotein
particles consisting of a multitude of protein and RNA subunits. We identify
sites of sequence processing, protein post-translational modifications, and the
assembly and stoichiometry of individual ribosomal proteins in four distinct
ribosomal particles of bacterial, plant and human origin. Amongst others, we
report extensive cysteine methylation in the zinc finger domain of the human S27
protein, the heptameric stoichiometry of the chloroplastic stalk complex, the
heterogeneous composition of human 40S ribosomal subunits and their association
to the CrPV, and HCV internal ribosome entry site RNAs.
PMID- 29950688
TI - Metabolites Re-programming and Physiological Changes Induced in Scenedesmus
regularis under Nitrate Treatment.
AB - Nitrate is required to maintain the growth and metabolism of plant and animals.
Nevertheless, in excess amount such as polluted water, its concentration can be
harmful to living organisms such as microalgae. Recently, studies on microalgae
response towards nutrient fluctuation are usually limited to lipid accumulation
for the production of biofuels, disregarding the other potential of microalgae to
be used in wastewater treatments and as source of important metabolites. Our
study therefore captures the need to investigate overall metabolite changes via
NMR spectroscopy approach coupled with multivariate data to understand the
complex molecular process under high (4X) and low (1/4X) concentrations of
nitrate ([Formula: see text]). NMR spectra with the aid of chemometric analysis
revealed contrasting metabolites makeup under abundance and limited nitrate
treatment. By using NMR technique, 43 types of metabolites and 8 types of fatty
acid chains were detected. Nevertheless, only 20 key changes were observed and 16
were down regulated in limited nitrate condition. This paper has demonstrated the
feasibility of NMR-based metabolomics approach to study the physiological impact
of changing environment such as pollution to the implications for growth and
productivity of microalgae population.
PMID- 29950689
TI - A taxonomic signature of obesity in a large study of American adults.
AB - Animal models suggest that gut microbiota contribute to obesity; however, a
consistent taxonomic signature of obesity has yet to be identified in humans. We
examined whether a taxonomic signature of obesity is present across two
independent study populations. We assessed gut microbiome from stool for 599
adults, by 16S rRNA gene sequencing. We compared gut microbiome diversity,
overall composition, and individual taxon abundance for obese (BMI >= 30 kg/m2),
overweight (25 <= BMI < 30), and healthy-weight participants (18.5 <= BMI < 25).
We found that gut species richness was reduced (p = 0.04), and overall
composition altered (p = 0.04), in obese (but not overweight) compared to healthy
weight participants. Obesity was characterized by increased abundance of class
Bacilli and its families Streptococcaceae and Lactobacillaceae, and decreased
abundance of several groups within class Clostridia, including
Christensenellaceae, Clostridiaceae, and Dehalobacteriaceae (q < 0.05). These
findings were consistent across two independent study populations. When random
forest models were trained on one population and tested on the other as well as a
previously published dataset, accuracy of obesity prediction was good (~70%). Our
large study identified a strong and consistent taxonomic signature of obesity.
Though our study is cross-sectional and causality cannot be determined,
identification of microbes associated with obesity can potentially provide
targets for obesity prevention and treatment.
PMID- 29950690
TI - Enhancing Surface Sensing Sensitivity of Metallic Nanostructures using Blue
Shifted Surface Plasmon Mode and Fano Resonance.
AB - Improving surface sensitivities of nanostructure-based plasmonic sensors is an
important issue to be addressed. Among the SPR measurements, the wavelength
interrogation is commonly utilized. We proposed using blue-shifted surface
plasmon mode and Fano resonance, caused by the coupling of a cavity mode (angle
independent) and the surface plasmon mode (angle-dependent) in a long-periodicity
silver nanoslit array, to increase surface (wavelength) sensitivities of metallic
nanostructures. It results in an improvement by at least a factor of 4 in the
spectral shift as compared to sensors operated under normal incidence. The
improved surface sensitivity was attributed to a high refractive index
sensitivity and the decrease of plasmonic evanescent field caused by two effects,
the Fano coupling and the blue-shifted resonance. These concepts can enhance the
sensing capability and be applicable to various metallic nanostructures with
periodicities.
PMID- 29950691
TI - The role of PANSS symptoms and adverse events in explaining the effects of
paliperidone on social functioning: a causal mediation analysis approach.
AB - To date, no study has evaluated the joint role of symptoms and adverse events as
mediators of the effect of second-generation antipsychotics on patients' social
functioning. We used recently developed methods for mediation analysis with
multiple mediators to clarify the interplay of adverse events and symptoms in
explaining the effects of paliperidone (R code for implementing the mediation
analysis for multiple mediators is provided). We used data from 490 participants
in a 6-week randomized dose-response trial that assigned three fixed dosages of
ER OROS paliperidone (3, 9, and 15 mg/day). The primary outcome was an
individual's score on the social performance scale assessed after 6 weeks. The
sum of Positive and Negative Syndrome Scale (PANSS), weight gain, and
extrapyramidal symptoms measured via the Simpson-Angus Scale after 5 weeks were
investigated as potential mediators and effect modifiers of treatment effects.
Results from mediation analyses showed that the improvements in social
functioning are partly explained by reduction in PANSS symptoms. Suggestive
evidence that adverse events could play a role as mediators was found. In
particular, weight gain displayed a non-linear relationship with social
functioning, whereby beneficial effects observed at small levels of weight gain
were reduced in the presence of excessive weight gain. In conclusion, we found
that the short-term effects of paliperidone on social functioning were dependent
on the successful reduction in PANSS symptoms and possibly the occurrence of
excessive weight gain, thus suggesting future directions for treatment and
interventions.
PMID- 29950692
TI - The impact of individual comorbidities on non-relapse mortality following
allogeneic hematopoietic stem cell transplantation.
AB - Comorbidity burden is a well-established risk factor for non-relapse mortality
(NRM) following allogeneic stem cell transplantation (allo-SCT). We evaluated
whether individual comorbidities could better characterize NRM risk. Furthermore,
given differing toxicity profiles of conditioning agents, we hypothesized that
the hazard of comorbidities is exerted in a regimen-specific manner. This
retrospective study included 875 adults treated with an allo-SCT. Six
conditioning regimens were considered. Across the entire cohort and within each
regimen, the hazard ratio (HR) for NRM associated with individual comorbidities
was assessed using multivariable Cox regressions. In the overall population,
renal dysfunction, hypoalbuminemia, and severe hepatic disease were associated
with the highest risk of NRM (HR 2.1, HR 1.9, HR 1.7, respectively). The risk
associated with specific comorbidities was modified by the conditioning regimen
and was not correlated with intensity. In patients conditioned with
fludarabine/busulfan (Flu/Bu4), NRM risk was increased with cardiac disease (HR
5.54). Severe pulmonary disease and a pre-existing infection were associated with
increased NRM risk in patients receiving fludarabine/melphalan (HR 4.9) and
fludarabine/treosulfan (HR 3.6), respectively. Comorbidities may exert effects
unique to particular conditioning regimens, suggesting that regimen selection
should be driven in part by specific comorbidities.
PMID- 29950693
TI - A prospective study on serum Cytokeratin (CK)-18 and CK18 fragments as biomarkers
of acute hepato-intestinal GVHD.
AB - Apoptotic intestinal crypt cells are pathognomonic of acute intestinal graft
versus host disease (GVHD). Serum levels of the apoptotic degradation product
cytokeratin-18 fragments (CK18F) were associated with acute hepato-intestinal
GVHD. Here we present a prospective clinical observational trial (NCT00935324)
investigating serum levels of total CK18 (tCK18) and apoptotic CK18F to predict
imminent acute hepato-intestinal GVHD and response to treatment. Total (t)CK18
and CK18F kinetics were measured before transplantation and in weekly intervals
thereafter. In total 109 patients were enrolled. Acute hepato-intestinal GVHD
grade I-IV was suspected in 36 patients (33%) at a median of 56 days post
transplant, 12 of these patients developed steroid-refractory GVHD. Both tCK18
and apoptotic CK18F increased at GVHD onset, and distinguished patients with
suspected acute hepato-intestinal GVHD who were negative in intestinal histology.
In patients with clinical acute hepato-intestinal GVHD, tCK18 significantly
raised already 7-14 days before symptom onset. In receiver operator
characteristics, areas under the curve at GVHD onset were 0.927 (p < 0.001) for
tCK18 and 0.875 (p < 0.001) for apoptotic CK18F for patients with proven hepato
intestinal acute GVHD. This prospective study validates CK18F and highlights
tCK18 as specific biomarkers suitable for improving prediction and diagnosis of
suspected imminent and clinically manifest acute hepato-intestinal GVHD.
PMID- 29950694
TI - Polycomb repressive complex 2 haploinsufficiency identifies a high-risk subgroup
of pediatric acute myeloid leukemia.
PMID- 29950695
TI - Author Correction: Convergent evolution of a modified, acetate-driven TCA cycle
in bacteria.
AB - In this Brief Communication, the authors omitted references to several previous
studies that have demonstrated that the TCA variant shown has also been found in
several other bacterial species, specifically among some anaerobic
Deltaproteobacteria. The Brief Communication focused on showing that this variant
is more widespread than previously known, particularly in animal-associated
bacteria. Using genetic approaches, Kwong et al. demonstrated this alternative
cycle in additional, distantly related organisms. Thus, the previous work does
not affect the results of the advance provided. However, the previous studies are
relevant to this topic and should have been cited, and Kwong et al. apologize for
this for the omission. Citations to several of the studies should have been
included as refs 9-13 in the text as shown.
PMID- 29950696
TI - Author Correction: Chemosynthetic symbionts of marine invertebrate animals are
capable of nitrogen fixation.
AB - In this Article, the completeness and number of contigs for draft genomes from
two individuals of Laxus oneistus are incorrect in the main text, although the
correct information is included in Table 1. The original and corrected versions
of the relevant sentence are shown in the correction notice.
PMID- 29950697
TI - Septicemia due to Streptococcus dysgalactiae subspecies dysgalactiae in vampire
bats (Desmodus rotundus).
AB - Beta-hemolytic Streptococcus dysgalactiae is a well-known pathogen for a wide
range of animals and humans. Two subspecies are recognized: (i) equisimilis,
associated to disease in horses and humans, and (ii) dysgalactiae mainly isolated
from animal illness with only a few humans' cases. This study describes the
isolation and characterization of Streptococcus dysgalactiae subsp. dysgalactiae
(SDSD) from vampire bats, maintained in captivity for research proposes. Animals
presented neurologic, respiratory and gastroenteric symptoms and sudden death.
Beta-hemolytic Gram-positive cocci were isolated in blood agar plates and further
characterized as Lancefield group C. All isolates were identified as S.
dysgalactiae by matrix-assisted laser desorption/ionization-time of flight (MALDI
TOF) mass spectrometry and subspecies dysgalactiae was confirmed by 16S rRNA
sequencing and phylogenetic analysis. Genotyping through SE-ALFP resulted in
three profiles (A1-A3) with one bat being infected by profiles A1 and A3. This is
the first report of SDSD causing illness in bats and especially in Desmodus
rotundus species.
PMID- 29950698
TI - Incentive motivation in pet dogs - preference for constant vs varied food
rewards.
AB - Recently, there has been a move towards positive reinforcement using food rewards
in animal training. By definition, rewards function as reinforcers if they
increase or maintain the frequency of behaviour that they follow. However, in
operant conditioning tasks animals frequently show systematic changes in
performance - in particular a reduction in responding over time. One suggested
strategy to avoid such performance decrements is to provide a variety of food
rewards, rather than the same food reward in all trials. The enhancement of
appetitive behaviour and consumption by reward variation is referred to as
'variety effect'. We investigated whether dogs preferred a variable or a constant
food reward in a concurrent two-choice test. Of 16 dogs, six subjects showed a
significant preference for the varied food reward and six for the constant food
reward, while four dogs exhibited no significant preference for either option. At
the group level, there was a significant effect of block: preference for the
varied food reward increased across six blocks of ten trials each. Thus, although
some individuals may prefer a single, favourite food reward in the short term,
introducing variation in reward types may maintain dogs' motivation in operant
tasks over a longer time period.
PMID- 29950699
TI - Butyrate produced by gut commensal bacteria activates TGF-beta1 expression
through the transcription factor SP1 in human intestinal epithelial cells.
AB - The intestinal microbiota contributes to the global wellbeing of their host by
their fundamental role in the induction and maintenance of a healthy immune
system. Commensal bacteria shape the mucosal immune system by influencing the
proportion and the activation state of anti-inflammatory regulatory T cells
(Treg) by metabolites that are still only partially unravelled. Microbiota
members such as Clostridiales provide a transforming growth factor beta (TGFbeta)
rich environment that promotes the accumulation of Treg cells in the gut. The
intestinal epithelial cells (IECs) take a central part in this process, as they
are a major source of TGFbeta1 upon bacterial colonisation. In this study, we
investigated which gut commensal bacteria were able to regulate the TGFB1 human
promoter in IECs using supernatants from cultured bacteria. We reported that
Firmicutes and Fusobacteria supernatants were the most potent TGFB1 modulators in
HT-29 cells. Furthermore, we demonstrated that butyrate was the main metabolite
in bacterial supernatants accounting for TGFbeta1 increase. This butyrate-driven
effect was independent of the G-protein coupled receptors GPR41, GPR43 and
GPR109a, the transporter MCT1 as well as the transcription factors NF-kappaB and
AP-1 present on TGFB1 promoter. Interestingly, HDAC inhibitors were inducing a
similar TGFB1 increase suggesting that butyrate acted through its HDAC inhibitor
properties. Finally, our results showed that SP1 was the main transcription
factor mediating the HDAC inhibitor effect of butyrate on TGFB1 expression. This
is, to our knowledge, the first characterisation of the mechanisms underlying
TGFB1 regulation in IEC by commensal bacteria derived butyrate.
PMID- 29950700
TI - Origin and classification of spontaneous discharges in mouse superficial dorsal
horn neurons.
AB - Superficial laminae of the spinal cord possess a considerable number of neurons
with spontaneous activity as reported in vivo and in vitro preparations of
several species. Such neurons may play a role in the development of the
nociceptive system and/or in the spinal coding of somatosensory signals. We have
used electrophysiological techniques in a horizontal spinal cord slice
preparation from adult mice to investigate how this activity is generated and
what are the main patterns of activity that can be found. The results show the
existence of neurons that fire regularly and irregularly. Within each of these
main types, it was possible to distinguish patterns of spontaneous activity
formed by single action potentials and different types of bursts according to
intra-burst firing frequency. Activity in neurons with irregular patterns was
blocked by a mixture of antagonists of the main neurotransmitter receptors
present in the cord. Approximately 82% of neurons with a regular firing pattern
were insensitive to synaptic antagonists but their activity was inhibited by
specific ion channel blockers. It is suggested that these neurons generate
endogenous activity due to the functional expression of hyperpolarisation
activated and persistent sodium currents driving the activity of irregular
neurons.
PMID- 29950701
TI - Elevated serum levels of bone sialoprotein during ICU treatment predict long-term
mortality in critically ill patients.
AB - Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding
LIgand, N-linked Glycoproteins) family, has recently be associated to
inflammatory and infectious diseases. We therefore measured BSP concentrations in
136 patients at admission to the intensive care unit (ICU) and 3 days of ICU. BSP
levels were compared to 36 healthy blood donors and correlated to clinical data.
In these analysis, BSP serum levels were strongly elevated at the time point of
admission to the ICU when compared to healthy controls. Moreover BSP
concentrations were significantly elevated after 3 days of treatment on the
intensive care unit. A further increase in BSP levels was detected in patients
with higher APACHE-II-scores and in patients with septic disease. While in most
patients, BSP levels decreased during the first three days of treatment on a
medical ICU, patients with persistently elevated BSP levels displayed an
unfavorable outcome. In these patients, persistently elevated BSP concentrations
were a superior predictor of mortality than established indicators of patient'
prognosis such as the SAPS2 or the APACHE-II score. In summary, our data argue
for a novel utility for BSP as a biomarker in patients treated on a medical ICU.
PMID- 29950702
TI - Hydrocarbon degradation and response of seafloor sediment bacterial community in
the northern Gulf of Mexico to light Louisiana sweet crude oil.
AB - The Deepwater Horizon (DWH) blowout resulted in the deposition to the seafloor of
up to 4.9% of 200 million gallons of oil released into the Gulf of Mexico. The
petroleum hydrocarbon concentrations near the wellhead were high immediately
after the spill, but returned to background levels a few years after the spill.
Microbial communities in the seafloor are thought to be responsible for the
degradation of hydrocarbons, however, our knowledge is primarily based upon gene
diversity surveys and hydrocarbon concentration in field sediment samples. Here,
we investigated the oil degradation potential and changes in bacterial community
by amending seafloor sediment collected near the DWH site with crude oil and both
oil and Corexit dispersant. Polycyclic aromatic hydrocarbons were rapidly
degraded during the first 30 days of incubation, while alkanes were degraded more
slowly. With the degradation of hydrocarbons, the relative abundances of
Colwelliaceae, Alteromonadaceae, Methylococales, Alcanivorax, Bacteriovorax, and
Phaeobacter increased remarkably. However, the abundances of oil-degrading
bacteria changed with oil chemistry. Colwelliaceae decreased with increasing oil
degradation, whereas Alcanivorax and Methylococcales increased considerably. We
assembled seven genomes from the metagenome, including ones belonging to
Colwellia, Alteromonadaceae, Rhodobacteraceae, the newly reported genus Woeseia,
and candidate phylum NC10, all of which possess a repertoire of genes for
hydrocarbon degradation. Moreover, genes related to hydrocarbon degradation were
highly enriched in the oiled treatment, suggesting that the hydrocarbons were
biodegraded, and that the indigenous microflora have a remarkable potential for
the natural attenuation of spilled oil in the deep-sea surface sediment.
PMID- 29950703
TI - Novel haptens and monoclonal antibodies with subnanomolar affinity for a
classical analytical target, ochratoxin A.
AB - Ochratoxin A is a potent toxic fungal metabolite whose undesirable presence in
food commodities constitutes a problem of public health, so it is strictly
regulated and controlled. For the first time, two derivatives of ochratoxin A
(OTAb and OTAd) functionalized through positions other than the native carboxyl
group of the mycotoxin, have been synthesized in order to better mimic, during
the immunization process, the steric and conformational properties of the target
analyte. Additionally, two conventional haptens making use of that native
carboxyl group for protein coupling (OTAe and OTAf) were also prepared as
controls for the purpose of comparison. The immunological performance in rabbits
of protein conjugates based on OTAb and OTAd overcome that of conjugates
employing OTAe and OTAf as haptens. After immunization of mice with OTAb and OTAd
conjugates, a collection of high-affinity monoclonal antibodies to ochratoxin A
was generated. In particular, one of those antibodies, the so-called OTAb#311, is
very likely the best antibody produced so far in terms of selectivity and
affinity to ochratoxin A.
PMID- 29950705
TI - Market watch: Upcoming catalysts in Q3 2018.
PMID- 29950706
TI - Autoimmune disease: Aryl hydrocarbon receptor suppresses inflammation.
PMID- 29950704
TI - In-vivo topical mucosal delivery of a fluorescent deoxy-glucose delineates
neoplasia from normal in a preclinical model of oral epithelial neoplasia.
AB - Metabolic imaging of oral cavity mucosal surfaces could benefit early detection
of oral squamous cell carcinoma (OSCC) and oral epithelial dysplasia (OED).
Fluorescent deoxy-glucose agents provide contrast for glucose metabolism similar
to 18FDG-PET imaging and allow use of optical imaging, which provides high
resolution and lower potential cost. However, in-vivo topical mucosal delivery of
fluorescent deoxy-glucose agents without injection or tissue resection has not
been shown. We introduce in-vivo optical imaging of neoplasia following mucosal
delivery of 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2
NBDG) in an OSCC/OED hamster model and demonstrate uptake into epithelium across
the mucosal surface without injection or disrupting the epithelium. 2-NBDG
fluorescence intensity following 30-minutes topical application was 6-fold and 4
fold higher in OSCC and OED, respectively, compared to normal mucosa. Receiver
operator characteristic analysis show 83% sensitivity and 73% specificity for
detection of neoplasia vs benign (normal and inflammation). Faster 2-NBDG
fluorescence temporal decay in neoplasia indicated higher uptake and glucose
metabolic rate than normal mucosa. Mucosal delivery of 2-NBDG by topical
application to the in-vivo oral surface is feasible and delineates neoplasia from
normal mucosa, providing in-vivo noninvasive molecular imaging of dysregulated
glucose metabolism, which could benefit preclinical studies of carcinogenesis or
be developed for use in early detection.
PMID- 29950707
TI - Infectious disease: Alphavirus receptor identified.
PMID- 29950708
TI - mRNA vaccines get another booster.
PMID- 29950709
TI - Amy Abernethy.
PMID- 29950711
TI - FDA approves Eli Lilly's baricitinib.
PMID- 29950710
TI - Cancer: Minimizing metastasis.
PMID- 29950712
TI - Ebola outbreak prompts experimental drug rollout.
PMID- 29950713
TI - First GPCR-directed antibody passes approval milestone.
PMID- 29950714
TI - Lead identification: The importance of residual complexity.
PMID- 29950715
TI - Identification of CTA-Based Predictive Findings for Temporary and Permanent
Neurological Dysfunction after Repair in Acute Type A Aortic Dissection.
AB - The aim of this study was to determine CT risk findings predictive of temporary
neurological dysfunction (TND) and permanent neurological dysfunction (PND) after
surgical repair for acute type A aortic dissection (ATAAD). A total of 255
patients (41 +/- 16 years, 79% male) with ATAAD underwent aortic CT angiography
(CTA) and surgical repair consecutively from January 2013 to June 2016. The CTA
findings of the 255 patients for the thoracic aorta and carotid artery were
analysed to identify risk factors predictive of TND and PND. Thirty-eight
patients (15%) suffered TND, and 18 (7%) exhibited PND. Common carotid artery
(CCA) dissection (OR = 4.63), lower enhancement of unilateral ICA (OR = 3.02) and
aortic arch tears (OR = 2.83) were predictors of postoperative TND, while PND was
best predicted by retrograde ascending aorta (aAO) dissection (OR = 5.62) and
aortic arch tears (OR = 6.74). In CCA dissection, the extent of the entire CCA
and proximal ICA (P = 0.014), a low-enhancement false lumen with re-entry (P =
0.000) and a severely narrowed true lumen without re-entry (P = 0.005)
significantly increased the risk of postoperative TND. In patients with ATAAD,
specific CT findings allow the individual risk of postoperative TND and PND to be
identified and may guide subsequent surgical management.
PMID- 29950716
TI - Author Correction: EWS-FLI1 increases transcription to cause R-loops and block
BRCA1 repair in Ewing sarcoma.
AB - In this Letter, the sentence beginning "This work was funded...." in the
Acknowledgements should have read "CPRIT (RP140105) to J.C.R." rather than "CPRIT
(RP150445) to J.C.R." This error has been corrected online.
PMID- 29950717
TI - Cryo-EM structure of an essential Plasmodium vivax invasion complex.
AB - Plasmodium vivax is the most widely distributed malaria parasite that infects
humans1. P. vivax invades reticulocytes exclusively, and successful entry depends
on specific interactions between the P. vivax reticulocyte-binding protein 2b
(PvRBP2b) and transferrin receptor 1 (TfR1)2. TfR1-deficient erythroid cells are
refractory to invasion by P. vivax, and anti-PvRBP2b monoclonal antibodies
inhibit reticulocyte binding and block P. vivax invasion in field isolates2. Here
we report a high-resolution cryo-electron microscopy structure of a ternary
complex of PvRBP2b bound to human TfR1 and transferrin, at 3.7 A resolution.
Mutational analyses show that PvRBP2b residues involved in complex formation are
conserved; this suggests that antigens could be designed that act across P. vivax
strains. Functional analyses of TfR1 highlight how P. vivax hijacks TfR1, an
essential housekeeping protein, by binding to sites that govern host specificity,
without affecting its cellular function of transporting iron. Crystal and
solution structures of PvRBP2b in complex with antibody fragments characterize
the inhibitory epitopes. Our results establish a structural framework for
understanding how P. vivax reticulocyte-binding protein engages its receptor and
the molecular mechanism of inhibitory monoclonal antibodies, providing important
information for the design of novel vaccine candidates.
PMID- 29950718
TI - Non-gravitational acceleration in the trajectory of 1I/2017 U1 ('Oumuamua).
AB - 'Oumuamua (1I/2017 U1) is the first known object of interstellar origin to have
entered the Solar System on an unbound and hyperbolic trajectory with respect to
the Sun1. Various physical observations collected during its visit to the Solar
System showed that it has an unusually elongated shape and a tumbling rotation
state1-4 and that the physical properties of its surface resemble those of
cometary nuclei5,6, even though it showed no evidence of cometary activity1,5,7.
The motion of all celestial bodies is governed mostly by gravity, but the
trajectories of comets can also be affected by non-gravitational forces due to
cometary outgassing8. Because non-gravitational accelerations are at least three
to four orders of magnitude weaker than gravitational acceleration, the detection
of any deviation from a purely gravity-driven trajectory requires high-quality
astrometry over a long arc. As a result, non-gravitational effects have been
measured on only a limited subset of the small-body population9. Here we report
the detection, at 30sigma significance, of non-gravitational acceleration in the
motion of 'Oumuamua. We analyse imaging data from extensive observations by
ground-based and orbiting facilities. This analysis rules out systematic biases
and shows that all astrometric data can be described once a non-gravitational
component representing a heliocentric radial acceleration proportional to r-2 or
r-1 (where r is the heliocentric distance) is included in the model. After ruling
out solar-radiation pressure, drag- and friction-like forces, interaction with
solar wind for a highly magnetized object, and geometric effects originating from
'Oumuamua potentially being composed of several spatially separated bodies or
having a pronounced offset between its photocentre and centre of mass, we find
comet-like outgassing to be a physically viable explanation, provided that
'Oumuamua has thermal properties similar to comets.
PMID- 29950719
TI - Induction of innate immune memory via microRNA targeting of chromatin remodelling
factors.
AB - Prolonged exposure to microbial products such as lipopolysaccharide can induce a
form of innate immune memory that blunts subsequent responses to unrelated
pathogens, known as lipopolysaccharide tolerance. Sepsis is a dysregulated
systemic immune response to disseminated infection that has a high mortality
rate. In some patients, sepsis results in a period of immunosuppression (known as
'immunoparalysis')1 characterized by reduced inflammatory cytokine output2,
increased secondary infection3 and an increased risk of organ failure and
mortality4. Lipopolysaccharide tolerance recapitulates several key features of
sepsis-associated immunosuppression5. Although various epigenetic changes have
previously been observed in tolerized macrophages6-8, the molecular basis of
tolerance, immunoparalysis and other forms of innate immune memory has remained
unclear. Here we perform a screen for tolerance-associated microRNAs and identify
miR-221 and miR-222 as regulators of the functional reprogramming of macrophages
during lipopolysaccharide tolerization. Prolonged stimulation with
lipopolysaccharide in mice leads to increased expression of miR-221 and mir-222,
both of which regulate brahma-related gene 1 (Brg1, also known as Smarca4). This
increased expression causes the transcriptional silencing of a subset of
inflammatory genes that depend on chromatin remodelling mediated by SWI/SNF
(switch/sucrose non-fermentable) and STAT (signal transducer and activator of
transcription), which in turn promotes tolerance. In patients with sepsis,
increased expression of miR-221 and miR-222 correlates with immunoparalysis and
increased organ damage. Our results show that specific microRNAs can regulate
macrophage tolerization and may serve as biomarkers of immunoparalysis and poor
prognosis in patients with sepsis.
PMID- 29950720
TI - OTULIN limits cell death and inflammation by deubiquitinating LUBAC.
AB - OTULIN (OTU deubiquitinase with linear linkage specificity) removes linear
polyubiquitin from proteins that have been modified by LUBAC (linear ubiquitin
chain assembly complex) and is critical for preventing auto-inflammatory
disease1,2 and embryonic lethality during mouse development3. Here we show that
OTULIN promotes rather than counteracts LUBAC activity by preventing its auto
ubiquitination with linear polyubiquitin. Thus, knock-in mice that express
catalytically inactive OTULIN, either constitutively or selectively in
endothelial cells, resembled LUBAC-deficient mice4 and died midgestation as a
result of cell death mediated by TNFR1 (tumour necrosis factor receptor 1) and
the kinase activity of RIPK1 (receptor-interacting protein kinase 1).
Inactivation of OTULIN in adult mice also caused pro-inflammatory cell death.
Accordingly, embryonic lethality and adult auto-inflammation were prevented by
the combined loss of cell death mediators: caspase 8 for apoptosis and RIPK3 for
necroptosis. Unexpectedly, OTULIN mutant mice that lacked caspase 8 and RIPK3
died in the perinatal period, exhibiting enhanced production of type I interferon
that was dependent on RIPK1. Collectively, our results indicate that OTULIN and
LUBAC function in a linear pathway, and highlight a previously unrecognized
interaction between linear ubiquitination, regulators of cell death, and
induction of type I interferon.
PMID- 29950721
TI - Low-temperature crystallization of granites and the implications for crustal
magmatism.
AB - The structure and composition of granites provide clues to the nature of silicic
volcanism, the formation of continents, and the rheological and thermal
properties of the Earth's upper crust as far back as the Hadean eon during the
nascent stages of the planet's formation1-4. The temperature of granite
crystallization underpins our thinking about many of these phenomena, but
evidence is emerging that this temperature may not be well constrained. The
prevailing paradigm holds that granitic mineral assemblages crystallize entirely
at or above about 650-700 degrees Celsius5-7. The granitoids of the Tuolumne
Intrusive Suite in California tell a different story. Here we show that quartz
crystals in Tuolumne samples record crystallization temperatures of 474-561
degrees Celsius. Titanium-in-quartz thermobarometry and diffusion modelling of
titanium concentrations in quartz indicate that a sizeable proportion of the
mineral assemblage of granitic rocks (for example, more than 80 per cent of the
quartz) crystallizes about 100-200 degrees Celsius below the accepted solidus.
This has widespread implications. Traditional models of magma formation require
high-temperature magma bodies, but new data8,9 suggest that volcanic rocks spend
most of their existence at low temperatures; because granites are the intrusive
complements of volcanic rocks, our downward revision of granite crystallization
temperatures supports the observations of cold magma storage. It also affects the
link between volcanoes, ore deposits and granites: ore bodies are fed by the
release of fluids from granites below them in the crustal column; thus, if
granitic fluids are hundreds of degrees cooler than previously thought, this has
implications for research on porphyry ore deposits. Geophysical interpretations
of the thermal structure of the crust and the temperature of active magmatic
systems will also be affected.
PMID- 29950722
TI - Robust relationship between air quality and infant mortality in Africa.
AB - Poor air quality is thought to be an important mortality risk factor globally1-3,
but there is little direct evidence from the developing world on how mortality
risk varies with changing exposure to ambient particulate matter. Current global
estimates apply exposure-response relationships that have been derived mostly
from wealthy, mid-latitude countries to spatial population data4, and these
estimates remain unvalidated across large portions of the globe. Here we combine
household survey-based information on the location and timing of nearly 1 million
births across sub-Saharan Africa with satellite-based estimates5 of exposure to
ambient respirable particulate matter with an aerodynamic diameter less than 2.5
MUm (PM2.5) to estimate the impact of air quality on mortality rates among
infants in Africa. We find that a 10 MUg m-3 increase in PM2.5 concentration is
associated with a 9% (95% confidence interval, 4-14%) rise in infant mortality
across the dataset. This effect has not declined over the last 15 years and does
not diminish with higher levels of household wealth. Our estimates suggest that
PM2.5 concentrations above minimum exposure levels were responsible for 22% (95%
confidence interval, 9-35%) of infant deaths in our 30 study countries and led to
449,000 (95% confidence interval, 194,000-709,000) additional deaths of infants
in 2015, an estimate that is more than three times higher than existing estimates
that attribute death of infants to poor air quality for these countries2,6.
Upward revision of disease-burden estimates in the studied countries in Africa
alone would result in a doubling of current estimates of global deaths of infants
that are associated with air pollution, and modest reductions in African PM2.5
exposures are predicted to have health benefits to infants that are larger than
most known health interventions.
PMID- 29950723
TI - Author Correction: Hypothalamic stem cells control ageing speed partly through
exosomal miRNAs.
AB - The microarray data generated and analysed in this Article have been uploaded to
the Gene Expression Omnibus (GEO) under accession number GSE113383 . Accordingly,
the 'Data availability' section of the Methods of the original Article has been
rephrased online.
PMID- 29950724
TI - Parasitic helminths induce fetal-like reversion in the intestinal stem cell
niche.
AB - Epithelial surfaces form critical barriers to the outside world and are
continuously renewed by adult stem cells1. Whereas dynamics of epithelial stem
cells during homeostasis are increasingly well understood, how stem cells are
redirected from a tissue-maintenance program to initiate repair after injury
remains unclear. Here we examined infection by Heligmosomoides polygyrus, a co
evolved pathosymbiont of mice, to assess the epithelial response to disruption of
the mucosal barrier. H. polygyrus disrupts tissue integrity by penetrating the
duodenal mucosa, where it develops while surrounded by a multicellular
granulomatous infiltrate2. Crypts overlying larvae-associated granulomas did not
express intestinal stem cell markers, including Lgr53, in spite of continued
epithelial proliferation. Granuloma-associated Lgr5- crypt epithelium activated
an interferon-gamma (IFN-gamma)-dependent transcriptional program, highlighted by
Sca-1 expression, and IFN-gamma-producing immune cells were found in granulomas.
A similar epithelial response accompanied systemic activation of immune cells,
intestinal irradiation, or ablation of Lgr5+ intestinal stem cells. When cultured
in vitro, granuloma-associated crypt cells formed spheroids similar to those
formed by fetal epithelium, and a sub-population of H. polygyrus-induced cells
activated a fetal-like transcriptional program, demonstrating that adult
intestinal tissues can repurpose aspects of fetal development. Therefore, re
initiation of the developmental program represents a fundamental mechanism by
which the intestinal crypt can remodel itself to sustain function after injury.
PMID- 29950726
TI - High speed of fork progression induces DNA replication stress and genomic
instability.
AB - Accurate replication of DNA requires stringent regulation to ensure genome
integrity. In human cells, thousands of origins of replication are coordinately
activated during S phase, and the velocity of replication forks is adjusted to
fully replicate DNA in pace with the cell cycle1. Replication stress induces fork
stalling and fuels genome instability2. The mechanistic basis of replication
stress remains poorly understood despite its emerging role in promoting cancer2.
Here we show that inhibition of poly(ADP-ribose) polymerase (PARP) increases the
speed of fork elongation and does not cause fork stalling, which is in contrast
to the accepted model in which inhibitors of PARP induce fork stalling and
collapse3. Aberrant acceleration of fork progression by 40% above the normal
velocity leads to DNA damage. Depletion of the treslin or MTBP proteins, which
are involved in origin firing, also increases fork speed above the tolerated
threshold, and induces the DNA damage response pathway. Mechanistically, we show
that poly(ADP-ribosyl)ation (PARylation) and the PCNA interactor p21Cip1 (p21)
are crucial modulators of fork progression. PARylation and p21 act as suppressors
of fork speed in a coordinated regulatory network that is orchestrated by the
PARP1 and p53 proteins. Moreover, at the fork level, PARylation acts as a sensor
of replication stress. During PARP inhibition, DNA lesions that induce fork
arrest and are normally resolved or repaired remain unrecognized by the
replication machinery. Conceptually, our results show that accelerated
replication fork progression represents a general mechanism that triggers
replication stress and the DNA damage response. Our findings contribute to a
better understanding of the mechanism of fork speed control, with implications
for genomic (in)stability and rational cancer treatment.
PMID- 29950725
TI - Structure of a human synaptic GABAA receptor.
AB - Fast inhibitory neurotransmission in the brain is principally mediated by the
neurotransmitter GABA (gamma-aminobutyric acid) and its synaptic target, the type
A GABA receptor (GABAA receptor). Dysfunction of this receptor results in
neurological disorders and mental illnesses including epilepsy, anxiety and
insomnia. The GABAA receptor is also a prolific target for therapeutic, illicit
and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and
ethanol. Here we present high-resolution cryo-electron microscopy structures of
the human alpha1beta2gamma2 GABAA receptor, the predominant isoform in the adult
brain, in complex with GABA and the benzodiazepine site antagonist flumazenil,
the first-line clinical treatment for benzodiazepine overdose. The receptor
architecture reveals unique heteromeric interactions for this important class of
inhibitory neurotransmitter receptor. This work provides a template for
understanding receptor modulation by GABA and benzodiazepines, and will assist
rational approaches to therapeutic targeting of this receptor for neurological
disorders and mental illness.
PMID- 29950727
TI - IL-23 secreted by myeloid cells drives castration-resistant prostate cancer.
AB - Patients with prostate cancer frequently show resistance to androgen-deprivation
therapy, a condition known as castration-resistant prostate cancer (CRPC).
Acquiring a better understanding of the mechanisms that control the development
of CRPC remains an unmet clinical need. The well-established dependency of cancer
cells on the tumour microenvironment indicates that the microenvironment might
control the emergence of CRPC. Here we identify IL-23 produced by myeloid-derived
suppressor cells (MDSCs) as a driver of CRPC in mice and patients with CRPC.
Mechanistically, IL-23 secreted by MDSCs can activate the androgen receptor
pathway in prostate tumour cells, promoting cell survival and proliferation in
androgen-deprived conditions. Intra-tumour MDSC infiltration and IL-23
concentration are increased in blood and tumour samples from patients with CRPC.
Antibody-mediated inactivation of IL-23 restored sensitivity to androgen
deprivation therapy in mice. Taken together, these results reveal that MDSCs
promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL
23 can oppose MDSC-mediated resistance to castration in prostate cancer and
synergize with standard therapies.
PMID- 29950728
TI - The helicase Ded1p controls use of near-cognate translation initiation codons in
5' UTRs.
AB - The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its
mammalian orthologue DDX3 are critical for the initiation of translation1.
Mutations in DDX3 are linked to tumorigenesis2-4 and intellectual disability5,
and the enzyme is targeted by a range of viruses6. How Ded1p and its orthologues
engage RNAs during the initiation of translation is unknown. Here we show, by
integrating transcriptome-wide analyses of translation, RNA structure and Ded1p
RNA binding, that the effects of Ded1p on the initiation of translation are
connected to near-cognate initiation codons in 5' untranslated regions. Ded1p
associates with the translation pre-initiation complex at the mRNA entry channel
and repressing the activity of Ded1p leads to the accumulation of RNA structure
in 5' untranslated regions, the initiation of translation from near-cognate start
codons immediately upstream of these structures and decreased protein synthesis
from the corresponding main open reading frames. The data reveal a program for
the regulation of translation that links Ded1p, the activation of near-cognate
start codons and mRNA structure. This program has a role in meiosis, in which a
marked decrease in the levels of Ded1p is accompanied by the activation of the
alternative translation initiation sites that are seen when the activity of Ded1p
is repressed. Our observations indicate that Ded1p affects translation initiation
by controlling the use of near-cognate initiation codons that are proximal to
mRNA structure in 5' untranslated regions.
PMID- 29950731
TI - [Surgery and surgeons, their historical evolution].
PMID- 29950729
TI - Acquired resistance to IDH inhibition through trans or cis dimer-interface
mutations.
AB - Somatic mutations in the isocitrate dehydrogenase 2 gene (IDH2) contribute to the
pathogenesis of acute myeloid leukaemia (AML) through the production of the
oncometabolite 2-hydroxyglutarate (2HG)1-8. Enasidenib (AG-221) is an allosteric
inhibitor that binds to the IDH2 dimer interface and blocks the production of 2HG
by IDH2 mutants9,10. In a phase I/II clinical trial, enasidenib inhibited the
production of 2HG and induced clinical responses in relapsed or refractory IDH2
mutant AML11. Here we describe two patients with IDH2-mutant AML who had a
clinical response to enasidenib followed by clinical resistance, disease
progression, and a recurrent increase in circulating levels of 2HG. We show that
therapeutic resistance is associated with the emergence of second-site IDH2
mutations in trans, such that the resistance mutations occurred in the IDH2
allele without the neomorphic R140Q mutation. The in trans mutations occurred at
glutamine 316 (Q316E) and isoleucine 319 (I319M), which are at the interface
where enasidenib binds to the IDH2 dimer. The expression of either of these
mutant disease alleles alone did not induce the production of 2HG; however, the
expression of the Q316E or I319M mutation together with the R140Q mutation in
trans allowed 2HG production that was resistant to inhibition by enasidenib.
Biochemical studies predicted that resistance to allosteric IDH inhibitors could
also occur via IDH dimer-interface mutations in cis, which was confirmed in a
patient with acquired resistance to the IDH1 inhibitor ivosidenib (AG-120). Our
observations uncover a mechanism of acquired resistance to a targeted therapy and
underscore the importance of 2HG production in the pathogenesis of IDH-mutant
malignancies.
PMID- 29950730
TI - Hippocampal neurogenesis confers stress resilience by inhibiting the ventral
dentate gyrus.
AB - Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by
environmental influences, and functionally implicated in behavioural responses to
stress and antidepressants1-4. However, how adult-born neurons regulate dentate
gyrus information processing to protect from stress-induced anxiety-like
behaviour is unknown. Here we show in mice that neurogenesis confers resilience
to chronic stress by inhibiting the activity of mature granule cells in the
ventral dentate gyrus (vDG), a subregion that is implicated in mood regulation.
We found that chemogenetic inhibition of adult-born neurons in the vDG promotes
susceptibility to social defeat stress, whereas increasing neurogenesis confers
resilience to chronic stress. By using in vivo calcium imaging to record neuronal
activity from large cell populations in the vDG, we show that increased
neurogenesis results in a decrease in the activity of stress-responsive cells
that are active preferentially during attacks or while mice explore anxiogenic
environments. These effects on dentate gyrus activity are necessary and
sufficient for stress resilience, as direct silencing of the vDG confers
resilience whereas excitation promotes susceptibility. Our results suggest that
the activity of the vDG may be a key factor in determining individual levels of
vulnerability to stress and related psychiatric disorders.
PMID- 29950732
TI - [Diverticulo de Zenker. Manejo endoscopico contra tecnica abierta. ?Cual es
mejor? Experiencia en el Hospital General de Mexico Dr. Eduardo Liceaga].
AB - Introduccion: El diverticulo de Zenker es una enfermedad rara en la poblacion
general. Su tratamiento puede llevarse a cabo mediante un enfoque endoscopico o
quirurgico. Objetivo: Reportar la experiencia en el manejo del diverticulo de
Zenker en un centro de ensenanza de tercer nivel. Metodos: Estudio retrospectivo,
transversal, descriptivo, en el que fueron analizados los expedientes de todos
los pacientes con diagnostico de diverticulo de Zenker desde la formacion de la
clinica de tracto digestivo superior del Hospital General de Mexico Dr. Eduardo
Liceaga. Resultados: Se encontraron 14 casos con diagnostico de diverticulo de
Zenker, 10 tratados con tecnica transoral y 4 por cirugia abierta. Se presentaron
tres recidivas en la tecnica transoral y ninguna con la tecnica abierta. En
cuanto a las complicaciones, hubo una lesion dental con la tecnica transoral y
una fistula esofagica con cirugia abierta, que fue manejada con sonda nasoyeyunal
colocada por endoscopia hasta el cierre espontaneo de la fistula. Conclusion: El
grapado transoral es una tecnica con buenos resultados esteticos, pero en nuestra
experiencia presenta mayor recurrencia que la cirugia abierta, por lo que debemos
realizar un seguimiento a largo plazo de nuestros pacientes. Background: Zenker
diverticulum is a rare disease in the general population. Its treatment can be
carried out by either an endoscopic or surgical approach. Objective: To report
the experience in the management of the Zenker diverticulum in a tertiary
education center. Methods: Retrospective, cross-sectional, descriptive study in
which the files of all patients with diagnosis of Zenker diverticulum were
analyzed from the formation of the upper digestive tract clinic of the General
Hospital of Mexico Dr. Eduardo Liceaga. Results: We found 14 cases with diagnosis
of Zenker diverticulum, 10 treated with transoral technique and 4 for open
surgery. Three recurrences in the transoral technique, no relapse with open
technique. In terms of complications, one dental lesion was presented in the
technique transoral, and one esophageal fistula in open surgery, managed with a
nasojejunal tube placed by endoscopy until the spontaneous closure of said
fistula. Conclusions: Transoral stapling is a technique with good aesthetic
results. However, in our experience, it has a greater recurrence than open
surgery, which is why we must carry out a long-term follow-up of our patients.
PMID- 29950733
TI - [Cambios en la salud sexual de los pacientes obesos tras cirugia bariatrica].
AB - Introduccion: Los objetivos del estudio fueron: 1) evaluar la salud sexual en
pacientes con obesidad grave/morbida candidatos a cirugia bariatrica; y 2)
valorar la evolucion de la salud sexual tras 12 meses de la cirugia. Metodo:
Estudio descriptivo, prospectivo desde febrero de 2011 hasta junio de 2014. Se
valoro la actividad sexual en los hombres a traves del cuestionario EVAS-H y la
funcion sexual en la mujer a traves de la escala FSM (44 pacientes). Resultados:
Durante el estudio basal en los hombres, un 21% de la muestra presento disfuncion
sexual en diferentes dimensiones, mientras que un 43% presento problemas de
eyaculacion precoz. Tras 12 meses de la intervencion, se observo un incremento de
la actividad sexual global (p = 0.026). En torno al 70-89% de las mujeres,
previamente a la cirugia, no presentaban trastorno. En la evolucion no se
observaron cambios medios relevantes (p > 0.05). Conclusiones: Los pacientes con
obesidad grave/morbida candidatos a cirugia bariatrica presentan alteraciones
considerables en diversas dimensiones de la salud sexual. Despues de 12 meses de
seguimiento, la salud sexual parece mejorar en los hombres. Introduction: The
aims of the study were: 1) to assess sexual health patients severe/morbid obesity
patients candidates for bariatric surgery; and 2) to assess sexual health
evolution after 12 months of surgery. Method: Descriptive, prospective study from
February 2011 to June 2014. Sexual activity in men was valued through EVAS-H
questionnaire and through FSM scale on women (44 patients). Results: During the
basal study in men, a 21% of the sample showed sexual disfunction in different
dimensions, while a 43% showed problems with premature ejaculation. 12 months
after surgery, global sexual activity was improved significantly (p = 0,026).
Approximately 70-89% of women presented no disturbance before surgery. No average
relevant changes were observed within the evolution (p > 0.05). Conclusions:
Morbid/severe obesity patients candidates to bariatric surgery, show considerable
alterations on diverse sexual health dimensions. After 12 months following
bariatric surgery, men's sexual health appears to improve.
PMID- 29950734
TI - Role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in
the treatment of gastric cancer.
AB - Patients with peritoneal carcinomatosis (PC) of gastric origin have a poor
prognosis of life with an average survival of 1-3 months. Systemic chemotherapy
has improved the survival of those patients with gastric metastatic cancer at 7
10 months. However, this benefit could not be reproduced in those patients with
PC. The current literature for the use of hyperthermic intraperitoneal
chemotherapy (HIPEC) for gastric PC has significant variation related to patient
selection, treatment intent (palliative vs. attempt at curative treatment),
surgical technique, intraperitoneal chemotherapy agent utilized, and systemic
chemotherapy administered adjuvantly. From the perspective of patient selection
for cytoreduction and HIPEC, patients with extensive PC are not candidates. In
addition, unresectable location would make a patient a poor candidate for
cytoreduction and HIPEC. Optimally, those with positive peritoneal cytology alone
could benefit most. However, the role of cytoreductive surgery and HIPEC in
patients with PC of gastric origin has not yet been clarified.
PMID- 29950735
TI - [Reconstruccion osea de defectos craneales secundarios a traumatismo con
implantes personalizados].
AB - Introduccion: Los defectos craneales secundarios a traumatismos son frecuentes.
Por lo comun se reparan de forma secundaria por sintomatologia como el sindrome
del paciente trepanado, por proteccion cerebral y por el aspecto cosmetico.
Historicamente se han utilizado diversos materiales para la reconstruccion. Casos
clinicos: Se presentan cinco casos de pacientes reconstruidos con implantes
personalizados de polieteretercetona (PEEK) o polimetilmetacrilato poroso (PMMA).
Las localizaciones afectaron el frontal, el borde orbitario superior y el techo
orbitario en cuatro casos, y la porcion lateral del frontal, la zona
temporoparietal y el borde del occipital en un caso. La reconstruccion en cuatro
pacientes fue entre 6 y 12 meses despues de la lesion, y en un caso despues de 25
anos. En dos casos se requirio expansion tisular antes de colocar el implante.
Resultados: Cuatro pacientes evolucionaron favorablemente, con mejoria de los
sintomas neurologicos, forma y contorno adecuados, asi como un proceso de
cicatrizacion adecuada de los colgajos de piel cabelluda. Un paciente presento
infeccion por Staphylococcus aureus, atribuida a la presencia de un mucocele y
una fistula de la via aerea a la cavidad craneal, lo que hizo necesario retirar
el implante. Conclusiones: Los implantes personalizados son un recurso util para
defectos oseos craneales. Brindan resultados satisfactorios desde el punto de
vista funcional y cosmetico. Deben tomarse precauciones respecto al tratamiento
de las lesiones que afecten el seno frontal, para evitar la comunicacion entre la
via aerea y la cavidad craneal. Introduction: Cranial defects due to trauma are
frequent. They are usually repaired in a secondary fashion due to features such
as syndrome of the trephined, for brain protection and for cosmetic purposes.
Historically, various materials have been used for reconstruction. Case reports:
Five cases of patients reconstructed with customized polyetheretherketone (PEEK)
o polymethyl methacrylate (PMMA) implants are presented. Defects involved the
frontal bone, superior orbital rim and orbital roof in four cases, and the
lateral area of the frontal bone, the temporoparietal area and the border of the
occipital bone in one. In four patients, reconstruction took place between 6 and
12 months after the injury; in one patient, after 25 years. Two cases required
tissue expansion before placing the implant. Results: Four patients evolved
favorably, with improvement in neurologic symptoms and adequate shape and
contour, plus adequate healing of the scalp flaps. One patient had an infection
due to Staphylococcus aureus, attributed to a mucocele and fistula between the
airway and the cranial cavity, leading to removal of the implant. Conclusions:
Customized implants are a useful resource for cranial defects. They offer
satisfactory results, both functional and cosmetic. Precautions should be taken
in treating injuries that involve the frontal sinus, to ensure there is no
communication between the airway and the cranial cavity.
PMID- 29950736
TI - [Perfil de expresion de Ki67 en lesiones melanociticas palmoplantares: estudio de
casos y controles].
AB - Introduccion: El melanoma acral lentiginoso es una neoplasia maligna que afecta a
poblacion predominantemente no caucasica. Debido al diagnostico tardio suele
tener mal pronostico, ademas de que se considera una neoplasia biologicamente mas
agresiva, incluso cuando se detecta tempranamente. Objetivo: Determinar la
expresion de Ki67 en el melanoma acral lentiginoso invasor y compararla con los
nevos acrales. Metodo: Estudio transversal, descriptivo, observacional. Se
realizo inmunohistoquimica con marcador Ki67 en 17 biopsias de melanoma acral
lentiginoso invasor (casos) y 17 biopsias de nevos palmoplantares (controles). Se
determino la expresion nuclear de Ki-67 y se comparo entre ambos grupos.
Resultados: La media de expresion de Ki67 fue del 8.5% en el grupo control y del
34% en el grupo de melanomas, siendo esta diferencia estadisticamente
significativa (p < 0.0001). Discusion: La expresion de Ki67 en los melanomas
acrales es considerablemente mayor que en los nevos acrales. El valor pronostico
del marcador Ki67 sigue siendo considerado controversial. Sin embargo, hay
estudios en los que en combinacion con otros marcadores se refuerza su valor
pronostico. Conclusiones: Por la gran diferencia en inmunorreactividad de Ki67
entre melanomas y nevos, la expresion de Ki67, referida como indice
proliferativo, podria ser considerada como factor pronostico incluso mas objetivo
que el indice mitotico. Background: Acral lentiginous melanoma is a malignant
neoplasm which appears in hands and feet. Acral lentiginous melanoma has an
unclear etiology, and usually affects non-Caucasian population. Because it is
frequently diagnosed lately, acral melanoma has bad prognosis; however, it is
biologically more aggressive than other clinicopathological types of melanoma,
even when diagnosed early. Objective: To determine the expression of Ki67 in
invasive lentiginous acral melanoma and to compare it with acral nevi. Method:
Cross-sectional, descriptive, observational study. Immunohistochemistry with Ki67
marker was performed on 17 biopsies of invasive lentiginous acral melanoma
(cases) and 17 biopsies of palmoplantar nevi (controls). Nuclear expression of Ki
67 was determined and both were compared between both groups. Results: The mean
expression of Ki67 was 8.5% in the control group, and 34% in the melanoma group,
which was statistically significant (p < 0.0001). Discussion: Ki67 expression in
acral lentiginous melanomas is higher than in acral nevi. Prognostic value of
Ki67 is still considered controversial. However, there are several studies where,
in combination with other markers, their prognostic value is reinforced.
Conclusions: Due to the wide gap in Ki67 expression between melanomas and nevi
showed in this study, Ki67 expression, referred to as a proliferative index,
could be considered as a prognostic factor even more objective than the mitotic
index.
PMID- 29950737
TI - [Metastasis cutanea de cancer de colon: una forma de presentacion inusual y
tardia a tener en cuenta].
AB - Introduccion: El cancer colorrectal es un gran problema de salud por su alta
incidencia y mortalidad. Las metastasis cutaneas son raras, con una incidencia <
5%. Caso clinico: Varon con antecedente de colectomia por neoplasia de colon que
6 anos despues presenta una lesion cutanea. La biopsia informa de metastasis
colonica, por lo que se realiza reseccion quirurgica radical. La anatomia
patologica confirma un adenocarcinoma moderadamente diferenciado compatible con
metastasis colonica. Discusion y conclusiones: Las metastasis cutaneas son raras
y cuando aparecen nos indican una enfermedad avanzada, por lo que es importante
un alto indice de sospecha en pacientes de riesgo para un diagnostico precoz.
Introduction: Colorectal cancer is a big health problem due to its high incidence
and mortality. Cutaneous metastases are rare with an incidence < 5%. Clinical
case: A male with a history of colectomy due to colon cancer, who 6 years later
presented a cutaneous lesion. The biopsy reported colonic metastasis, so radical
surgical resection was performed. The pathological anatomy confirmed a moderately
differentiated adenocarcinoma compatible with colonic metastasis. Discussion and
conclusion: Cutaneous metastases are rare and when they appear they indicate an
advanced disease, for that reason is important a high index of suspicion in
patients at risk, for an early diagnosis.
PMID- 29950738
TI - [Resultados quirurgicos de histerectomia radical laparoscopica en pacientes con
cancer de cervix en etapa temprana: experiencia inicial en Instituto de Cancer].
AB - Antecedentes: La histerectomia radical abierta con linfadenectomia pelvica
bilateral es el tratamiento estandar para el cancer de cervix uterino (CACU) en
etapas temprana (1A2-1B1); la histerectomia radical por laparoscopia (HRL) es una
opcion segura y viable. Objetivo: Evaluar la seguridad y la factibilidad de la
HRL en un centro hospitalario de atencion de cancer. Metodo: Estudio
retrospectivo que incluyo 17 pacientes con CACU en etapa temprana intervenidas
con HRL entre abril de 2013 y noviembre de 2016 en el Instituto Nacional de
Cancerologia de Mexico. Resultados: Las 17 pacientes se encontraban en etapa
clinica IB1, en 10 (58.8%) fue subtipo epidermoide, en 4 (23.5%) adenocarcinoma y
en 3 (17.6%) adenoescamoso. La media de edad fue de 42 +/- 8 anos. El tamano del
tumor fue de 2.3 +/- 0.9 cm, y en el 94.1% los margenes quirurgicos estaban
libres de enfermedad. El promedio de tiempo operatorio fue de 341 +/- 65 minutos,
con una perdida sanguinea de 107 +/- 64 ml, no requirieron trasfusion sanguinea y
no hubo conversion a cirugia abierta. La media de estancia hospitalaria fue de
2.7 dias (rango: 2-7 dias). No se presentaron complicaciones intraoperatorias ni
posoperatorias. Conclusiones: La HRL es una alternativa segura y confiable para
el tratamiento del CACU en etapa temprana. Background: Open radical hysterectomy
with bilateral pelvic lymphadenectomy is the standard treatment in early stages
(1A2-1B1) of uterine cervical cancer (UCC); laparoscopic radical hysterectomy
(LRH) is a safe and viable option. Objective: To evaluate the safety and
feasibility of LRH in a hospital cancer care center. Method: Retrospective study
that included the first 17 patients with UCC in an early stage operated with LRH
in the period from April 2013 to November 2016 at the National Cancer Institute
of Mexico. Results: The 17 patients were stage IB1 clinical, of which 10 (58.8%)
was epidermoid subtype, 4 (23.5%) adenocarcinoma and 3 (17.6%) adenoescamoso. The
mean age was 42 +/- 8 years. The tumor size was 2.3 +/- 0.9 cm, and in 94.1% the
surgical margins were free of disease. The average operative time was 341 +/- 65
minutes and blood loss of 107 +/- 64 ml, no patient required blood transfusion
and there was no case of conversion to open surgery. The average length of
hospital stay was 2.7 days (range: 2-7 days). There were no intraoperative or
postoperative complications. Conclusions: LRH is a safe and reliable alternative
for the treatment of early stage UCC.
PMID- 29950739
TI - [Tecnologias de la informacion en la formacion de evaluadores del Programa
Hospital Seguro en Mexico].
AB - Objetivo: Describir el proceso para la formacion de evaluadores del Programa
Hospital Seguro centrado en el uso de las tecnologias de la informacion. Metodo:
Estudio observacional descriptivo en el que se analiza la participacion dentro
del nuevo curso de evaluadores del Programa Hospital Seguro. Resultados: Se
inscribieron 1323 participantes, de los cuales aprobaron 298 (18%); la
calificacion media fue de 8.85. Conclusiones: La plataforma educativa tipo Moodle
fue de utilidad para la capacitacion del Programa Hospital Seguro. Se tendrian
que mejorar los criterios de participacion de los alumnos a fin de incrementar la
eficiencia terminal. Objective: To describe the process for the training of
evaluators of the safe hospital program in the use of ICT. Method: Descriptive
observational study in which the participation in the new course of appraisers of
the safe hospital program is analyzed. Results: 1323 participants registered of
which 298 (18%) passed; the average grade was 8.85. Conclusions: The Moodle type
educational platform was useful for the training of the Safe Hospital Program.
The criteria for student participation would have to be improved in order to
increase terminal efficiency.
PMID- 29950740
TI - [Incidencia de la operacion cesarea segun la clasificacion de Robson en el
Servicio de Ginecologia y Obstetricia del Hospital Gral. Dr. Fernando Quiroz
Gutierrez del Instituto de Seguridad Social al Servicio de los Trabajadores del
Estado].
AB - Introduccion: El numero de cesareas en todo el mundo se ha incrementado de forma
importante y nuestro pais no es la excepcion. En algunos lugares se supera el 60%
de cesareas en relacion al parto vaginal. No existe una clasificacion adecuada
para el analisis de este incremento. La clasificacion de los 10 grupos de Robson
se basa en cuatro pilares: a) antecedentes obstetricos; b) progreso del parto; c)
categoria del embarazo; y d) edad gestacional. Sugerimos utilizar la
clasificacion de Robson para determinar que grupo de mujeres embarazadas
contribuyen mas al total de cesareas en nuestra institucion. Metodo: Estudio
retrospectivo, descriptivo, transversal, observacional, de 2014 al 2016,
incluyendo a todas las embarazadas con mas de 27 semanas de gestacion. Se
resolvio el embarazo a 706 mujeres con un porcentaje de cesarea del 65.29%. El
promedio de edad fue de 31 +/- 4.2 anos, y el de la edad gestacional fue de 38.5
+/- 6.7 semanas. Eran primigestas el 47%. La indicacion materna mas frecuente de
cirugia fue por cesarea iterativa, y la fetal por distocia de presentacion. En
cuanto a la ubicacion del mayor numero de pacientes dentro de la clasificacion de
Robson, fue el grupo 5 con un 21.24%, seguido del grupo 2 con un 13.88% y del
grupo 1 con un 9.6%. Conclusion: La existencia de cicatriz uterina previa fue el
factor determinante en la mayor parte de las cesareas. Sugerimos incidir sobre la
indicacion de la primera cesarea y asi disminuir cicatrices uterinas.
Introduction: The increase of cesarean sections worldwide has increased
significantly, our country is no exception, in some places it exceeds 60% of
cesarean sections in relation to vaginal delivery, there is no adequate
classification for the analysis of this increase. The classification of the 10
groups of Robson is based on four pillars: a) obstetric history; b) progress of
labor; c) category of pregnancy; and d) gestational age. We suggest using
Robson's classification to determine which group of pregnant women contribute
most to the total number of cesareans in our institution. Method: This
retrospective, descriptive, cross-sectional, observational study was conducted
from 2014 to 2016, all pregnant women with more than 27 weeks' gestation were
included. Pregnancy was resolved in 706 women with a caesarean section of 65.29%,
mean age was 31 +/- 4.2 years, and gestational age 38.5 +/- 6.7 weeks. 46.74%
were primiparous. The most frequent maternal indication for surgery was by
iterative cesarean section and the fetal one was due to presentation dystocia, as
for the location of the patients within the Robson classification was group 5
with 21.24%, group 2 with 13.88% and the 1 with 9.6%. Conclusion: The previous
uterine scarring was the determining factor in most of the cesarean sections, we
suggest to influence the indication of the first cesarean section and thus to
avoid uterine scars.
PMID- 29950741
TI - [Identificacion de farmacos reguladores de la actividad del promotor Egr-1 en
fibroblastos humanos transducidos con AdDeltaegr-1-Luc7].
AB - Introduccion: La proteina de respuesta temprana a crecimiento 1 (EGR-1) es un
factor de transcripcion involucrado en la diferenciacion y la proliferacion
celulares, cuya expresion es regulada por su promotor en respuesta a diversos
factores fisicos y quimicos, y a farmacos. Aqui se describen algunos de los
principales efectos de los farmacos esteroides y del factor de crecimiento
epitelial 1 (EGF-1) sobre la actividad del promotor, mediante un sistema
reportero transducido por el adenovirus AdDeltaegr-1-Luc7 en fibroblastos
primarios humanos. Metodo: Los fibroblastos primarios humanos fueron cultivados
en pase 5, transducidos con AdDeltaegr-1-Luc7 y expuestos a betametasona,
hidrocortisona, dexametasona, testosterona, beta-estradiol y EGF-1 durante 1, 3 y
6 horas. La actividad de reportero fue cuantificada por luminometria y ajustada a
la concentracion de proteinas totales. Resultados: La actividad del promotor en
presencia de betametasona, hidrocortisona, dexametasona, testosterona y beta
estradiol fue similar a la actividad basal del promotor a las 1, 3 y 6 horas. El
control positivo mostro una actividad 17.8 veces mayor a las 6 horas (p <= 0.05).
De manera similar, las celulas expuestas a EGF-1 mostraron una actividad 22.07
veces mayor que las celulas sin farmaco. Conclusion: La actividad del promotor
Egr-1 en fibroblastos humanos es regulada negativamente por los farmacos
esteroides y positivamente por el EGF-1. Introduction: The early growth response
protein (EGR-1) is a transcription factor involved in cell differentiation and
proliferation, whose expression is regulated by its promoter in response to
various physical, chemical and drug factors. Hereby, we describe some of the main
effects of steroid drugs and EGF-1 on promoter activity, through a reporter
system transduced by AdDeltaegr-1-Luc7 in human primary fibroblasts (HPF).
Methods: Human primary fibroblasts transduced with AdDeltaegr-1-Luc7 were exposed
to betamethasone, hydrocortisone, dexamethasone, testosterone, beta-estradiol,
and EGF-1 during 1, 3 and 6 h. Reporter assay was quantified by luminometry.
Results: The activity of the promoter in presence of betamethasone,
hydrocortisone, dexamethasone, testosterone and beta-estradiol were similar to
the basal activity of the promoter at 1, 3 and 6 h. The positive control showed
an activity 17.8 folds higher (p <= 0.05) at 6 h. EGF-1 showed activity of 22.07
folds greater than cells without drug. Conclusion: The activity of the EGR-1
promoter in human fibroblasts is negatively regulated by steroid drugs and
positively by the EGF-1.
PMID- 29950742
TI - [Uso de etamsilato para reducir el sangrado posoperatorio y el indice de
transfusion en la artroplastia total de cadera. Ensayo clinico controlado].
AB - Antecedentes: El sangrado secundario es una de las principales causas de
morbilidad despues de la cirugia. El etamsilato se ha utilizado con buenos
resultados para disminuir el sangrado en diversas patologias, como metrorragias,
sangrado intraventricular, prostatectomias, cirugias de catarata y
amigdalectomias. El objetivo de este estudio fue evaluar la efectividad del
etamsilato para disminuir el sangrado en la cirugia de reemplazo total de cadera.
Metodo: La poblacion se dividio en dos grupos. En el grupo control se realizo la
hemostasia de manera convencional; en el grupo experimental se administro
etamsilato. Resultados: Se incluyeron 34 pacientes, de los cuales 17 fueron
aleatorizados al grupo de etamsilato y 17 al grupo control. No hubo diferencias
en las caracteristicas de la poblacion entre los dos grupos. Al comparar los
valores de hemoglobina preoperatoria y a las 24, 48 y 72 horas posquirurgicas
entre ambos grupos, no se encontraron diferencias estadisticamente
significativas. Tampoco hubo diferencia en el hematocrito ni en la cuantificacion
del gasto por drenaje a las 24 y 48 horas. Hubo tres pacientes transfundidos en
el grupo de etamsilato y siete en el grupo de control, lo cual no difirio
significativamente (p = 0.62). Conclusion: En este estudio no se demostro un
efecto sobre la reduccion de la hemorragia en pacientes sometidos a reemplazo
total de cadera con el uso de etamsilato. Background: Secondary bleeding is one
of the leading causes of morbidity after the surgery. Ethamsylate has been used
with good results to decrease bleeding in various pathologies such as
metrorrhagia, intraventricular bleeding, prostatectomies, cataract surgeries and
tonsillectomies. The objective of this study was to evaluate the effectiveness of
the hemostatic agent ethamsylate to decrease bleeding in total hip replacement
surgery. Method: The population were divided into two groups, in the control
group was performed the hemostasis conventionally; in the experimental group
ethamsylate was administered. Results: A total of 34 patients were included, of
whom 17 were randomized to the group of ethamsylate and 17 randomized to the
control group. There were no differences in the characteristics of the population
between the two groups. Comparing preoperative hemoglobin levels and at 24, 48
and 72 postsurgical hours between the control group and ethamsylate group there
was no statistically significant difference. There was also no difference in the
levels of hematocrit. In the quantification of expenditure by the drainage there
was no difference between the groups at 24 and 48 hours. There were three
patients transfused in the ethamsylate group and seven in the control group,
which did not differ significantly (p = 0.62). Conclusion: An effect on the
reduction of bleeding in patients undergoing total hip replacement with the use
of hemostatic agent ethamsylate was not demonstrated in this study.
PMID- 29950743
TI - [Prevalencia y factores de riesgo para lesiones premalignas en pacientes menores
de 55 anos sometidos a colonoscopia en un hospital de tercer nivel].
AB - Antecedentes: El cancer colorrectal es causa importante de mortalidad y la
colonoscopia es efectiva para reducir su incidencia y mejorar la supervivencia
con la reseccion de las lesiones precursoras. Objetivo: Determinar la
prevalencia, las caracteristicas y la histologia de las lesiones en pacientes <
55 anos en un hospital de tercer nivel. Metodo: Se realizo un estudio
retrospectivo y observacional de enero de 2010 a diciembre de 2014 en el Hospital
de Especialidades del Centro Medico Nacional Siglo XXI, Instituto Mexicano del
Seguro Social, con el reporte de 555 colonoscopias y los datos clinicos de las
historias hospitalarias de los pacientes incluidos en el estudio. Resultados: Los
hallazgos fueron lesiones premalignas en el 40% de los pacientes, con polipos en
98 casos y con un tamano de 5.2 mm; de ellos, el 54% se localizaron en el colon,
el 24% en el sigmoides, el 27% en el recto y el 1% en el ano. En los reportes se
observo una prevalencia del 63% de polipos neoplasicos (riesgo relativo [RR]:
2.3; intervalo de confianza del 95% [IC 95%]: 1.5-3.7) en pacientes con
antecedente de tabaquismo, y del 42% (RR: 1.8; IC 95%: 1.2-2.6) con antecedente
de consumo de alcohol. Conclusiones: La prevalencia de lesiones premalignas es
similar para los menores de 55 anos. Esto indica la importancia del diagnostico
oportuno y de evitar la progresion. Seria conveniente extender el seguimiento a
hospitales de segundo nivel en pacientes con factores de riesgo para ampliar lo
reportado y contribuir a mejorar los resultados en la sanidad publica.
Background: Colorectal cancer is an important cause of mortality, colonoscopy is
effective to reduce its incidence and improve survival with the resection of
premalignant lesions. Objective: To determine the prevalence, characteristics and
histology of lesions in patients younger than 55 years of age in a tertiary
hospital. Method: This is a retrospective observational study, we colected data
at the Hospital de Especialidades del Centro Medico Nacional Siglo XXI, Instituto
Mexicano del Seguro Social, with the report of 555 colonoscopies, and clinical
data from the hospital archives of medic histories of selected patients. Results:
Premalignant lesions were found on 40% of the patients. The findings were polyps
in 98 cases with a size of 5.2 mm; 54% were located in the colon, 24% in the
sigmoid, 27% in the rectum and 1% in the anus. A prevalence of 63% of neoplastic
polyps was observed (RR: 2.3; 95% CI: 1.5-3.7) in smokers; and 42% (RR: 1.8; 95%
CI: 1.2-2.6) in patients with alcohol consumption. Conclusions: The prevalence
for premalignant lesions is similar for patients under 55 years of age. This
highlights the importance of early diagnosis and avoiding progression. It would
be convenient to extend the follow-up to second-level hospitals in patients with
risk factors to contribute to improvement of public health system outcomes.
PMID- 29950744
TI - [Psychotic and quasi-psychotic atypical experiences in Puerto Rican depressed
adolescents: Prevalence and related factors].
AB - The prevalence of psychotic and quasi-psychotic atypical experiences was
estimated and its correlates were identified in 162 Puerto Rican adolescents (13
to 17.5 years old). Depressive symptoms, suicidal ideation, as well as the
presence or history of atypical experiences, traumatic events and maltreatment or
abuse were evaluated. Atypical experiences were related (p<.05) to gender
(female), physical illness, history of traumatic events, history of treatment for
depression, as well as to high depressive symptomatology and suicidal ideation.
Traumatic events, pharmacological treatment for depression, and severity of
suicidal ideation were significant predictors of the total experiences reported.
Findings confirm that most experiences reported were definitely non-psychotic.
The implications for the assessment and treatment of depressed youth are
discussed.
PMID- 29950745
TI - Titanium Dioxide Nanoparticle Circulation in an Aquatic Ecosystem.
AB - Nanotechnology is a dynamically developing field of scientific and industrial
interest across the entire world, and the commercialization of nanoparticles
(NPs) is rapidly expanding. Incorporation of nanotechnologies into a range of
manufactured goods results in increasing concern regarding the subsequent release
of engineered NPs into the environment. One of the biggest threats of using NPs
is the transfer and magnification of these particles in the trophic chain. The
aim of the studies was the evaluation of the distribution of TiO2 NP
contamination in the aquatic ecosystem under laboratory conditions.
Bioaccumulation of TiO2 NPs by plants (Elodea canadensis) and fish (Danio rerio)
in the source of contamination was investigated. The studies were focused on the
consequences of short-term water contamination with TiO2 NPs and the secondary
contamination of the components of the investigated model ecosystem (plants,
sediments). It was found that in the fish and the plants exposed to NP
contamination, the amount of Ti was higher than in the control, indicating an
effective bioaccumulation of NPs or ions originating from NPs. It was clearly
shown that the NPs present in the sediments are available to plants and fish.
Additionally, the aquatic plants, an important trophic level in the food chain,
can accumulate NPs and be a source of NPs for higher organisms. It was concluded
that even an incidental contamination of water by NPs may result in long-term
consequences induced by the release of NPs.
PMID- 29950746
TI - European and Mediterranean hydroclimate responses to tropical volcanic forcing
over the last millennium.
AB - Volcanic eruptions have global climate impacts, but their effect on the
hydrologic cycle is poorly understood. We use a modified version of superposed
epoch analysis, an eruption year list collated from multiple datasets, and
seasonal paleoclimate reconstructions (soil moisture, precipitation, geopotential
heights, and temperature) to investigate volcanic forcing of spring and summer
hydroclimate over Europe and the Mediterranean over the last millennium. In the
western Mediterranean, wet conditions occur in the eruption year and the
following 3 years. Conversely, northwestern Europe and the British Isles
experience dry conditions in response to volcanic eruptions, with the largest
moisture deficits in post-eruption years 2 and 3. The precipitation response
occurs primarily in late spring and early summer (April-July), a pattern that
strongly resembles the negative phase of the East Atlantic Pattern. Modulated by
this mode of climate variability, eruptions force significant, widespread, and
heterogeneous hydroclimate responses across Europe and the Mediterranean.
PMID- 29950747
TI - Quantification of lithium at ppm level in geological samples using nuclear
reaction analysis.
AB - Proton-induced reaction (p,alpha) is one type of nuclear reaction analysis (NRA)
suitable especially for light element quantification. In the case of lithium
quantification presented in this work, accelerated protons with an energy about
of 850 keV were used to induce the 7Li(p,alpha)4He reaction in standard reference
and geological samples such as tourmaline and other Li-minerals. It is shown that
this technique for lithium quantification allowed for measurement of
concentrations down below one ppm. The possibility to relate the lithium content
with the boron content in a single analysis was also demonstrated using
tourmaline samples, both in absolute concentration and in lateral distribution.
In addition, Particle induced X-ray emission (PIXE) was utilized as a
complementary IBA technique for simultaneous mapping of elements heavier than
sodium.
PMID- 29950748
TI - The effect of gamma irradiation on the structural properties of olivine.
AB - Gamma irradiation studies of (Mg0.905Fe0.095)2SiO4 olivine were performed using X
ray fluorescence method, X-ray diffraction, Raman and Mossbauer spectroscopy. The
absorbed doses were 300, 600 and 1000 Gy. Small irradiation doses cause an
increase of lattice vibrations and small deformation of both M1 and M2
octahedron. The observed effect is similar to the results expose to high
temperature. However, the small deformation takes place only in unit cell of
Olivine's structure.
PMID- 29950749
TI - Redox interactions of technetium with neptunium in acid solutions.
AB - Redox interaction of reduced technetium forms and technetium(VII) with
neptunium(III), neptunium(IV) and neptunium(VI) have been investigated using
electrochemical and spectroscopic (Vis-NIR) techniques. The neptunium species
most stable in 4 M H2SO4, i.e. Np(IV) ions, do not reduce Tc(VII) in contrast to
Np(VI) ions which oxidize Tc(IV) species to Tc(VII). The interaction of
pertechnetates with Np(III) leads to formation of Tc(IV) species. The Vis-NIR
measurements showed the generation of intermediate Tc(V) and Np(V) forms during
the oxidation of Tc(IV) and competitive reduction of Np(VI). Tc(V) and Np(V)
forms are characterised by the bands at 460 and 980 nm respectively.
PMID- 29950750
TI - Chemical interaction between sea-salt and tellurium, between 300 and 1180 K.
AB - As an emergency action during the Fukushima accident, seawater was used to
maintain cooling. To evaluate the effect of the salt on fission-products, sodium
chloride, and tellurium were heated together using different ratios in different
atmospheres (inert or oxidizing) using thermogravimetric analysis. The experiment
under inert conditions showed no indication of interaction. However, under
oxidizing conditions an interaction for all samples was observed that prevented
an otherwise observed mass increase of the tellurium reference. The change in the
appearance of the samples at increasing temperatures was studied by heating them
in a furnace.
PMID- 29950751
TI - In vivo observation of transient photoreceptor movement correlated with oblique
light stimulation.
AB - Rod-dominated transient retinal phototropism (TRP) has been observed in freshly
isolated retinas, promising a noninvasive biomarker for high resolution
assessment of retinal physiology. However, in vivo mapping of TRP is challenging
due to its fast time course and sub-cellular signal magnitude. By developing a
line-scanning and virtually structured detection based super-resolution
ophthalmoscope, we report here in vivo observation of TRP in frog retina. In vivo
characterization of TRP time course and magnitude were implemented by using
variable light stimulus intensities.
PMID- 29950752
TI - Decent Living Standards: Material Prerequisites for Human Wellbeing.
AB - We define a set of universal, irreducible and essential set of material
conditions for achieving basic human wellbeing, along with indicators and
quantitative thresholds, which can be operationalized for societies based on
local customs and preferences. We draw support for this decent living standard
(DLS) from different accounts of basic justice, including the capability approach
and basic needs. The DLS goes beyond existing multidimensional poverty indicators
by comprehensively addressing living conditions and the means of social
participation. The DLS offers a normative basis to develop minimum wage and
reference budgets, and to assess the environmental impacts, such as climate
change, of eradicating poverty.
PMID- 29950753
TI - Social Quality and Health: Examining Individual and Neighbourhood Contextual
Effects Using a Multilevel Modelling Approach.
AB - Social quality focusses on the nature of 'the social', arguing that people are
realised as social beings through interacting with a range of collectives, both
from the formal world of systems and the informal lifeworld. Four conditional
factors are necessary for this to occur, which at the same time are assumed to
influence health and well-being: socio-economic security, social cohesion, social
inclusion and social empowerment. In this paper we test the utility of social
quality in explaining self-rated health as a response to arguments that the
social determinants of health (SDH) framework often lacks a theoretical basis. We
use multilevel models to analyse national English and Welsh data (the Citizenship
Survey) to test for both individual- and neighbour-level affects. Our key
findings are that (1) neighbourhood contextual (cross-level) effects are present
with respect to collective action, personal trust, cross-cutting ties, income
sufficiency, and income security; (2) measures of national, community and
personal identity as indicators of social cohesion show clear associations with
health alongside more common measures such as trust; (3) the security aspects of
socioeconomic determinants are especially important (housing security, income
sufficiency, and income security); (4) social rights, including institutional
rights but especially civil rights have effects of particularly large magnitude.
Social quality offers a theoretically-driven perspective on the SDH which has
important policy implications and suggests a number of promising avenues for
future research.
PMID- 29950754
TI - Distinguishing between apparent and actual randomness: a preliminary examination
with Australian ants.
AB - Abstract: The correlated random walk paradigm is the dominant conceptual
framework for modeling animal movement patterns. Nonetheless, we do not know
whether the randomness is apparent or actual. Apparent randomness could result
from individuals reacting to environmental cues and their internal states in
accordance with some set of behavioral rules. Here, we show how apparent
randomness can result from one simple kind of algorithmic response to
environmental cues. This results in an exponential step-length distribution in
homogeneous environments and in generalized stretched exponential step-length
distributions in more complex fractal environments. We find support for these
predictions in the movement patterns of the Australian bull ant Myrmecia midas
searching on natural surfaces and on artificial uniform and quasi-fractal
surfaces. The bull ants spread their search significantly farther on the quasi
fractal surface than on the uniform surface, showing that search characteristics
differed as a function of the substrate on which ants are searching. Further
tentative support comes from a re-analysis of Australian desert ants Melophorus
bagoti moving on smoothed-over sand and on a more strongly textured surface. Our
findings call for more experimental studies on different surfaces to test the
surprising predicted linkage between fractal dimension and the exponent in the
step-length distribution. Significance statement: Animal search patterns often
appear to be irregular and erratic. This behavior is captured by random walk
models. Despite their considerable successes, extrapolation and prediction beyond
observations remain questionable because the true nature and interpretation of
the randomness in these models have until now been elusive. Here, we show how
apparent randomness can result from simple algorithmic responses to environmental
cues. Distinctive predictions from our theory find support in analyses of the
search patterns of two species of Australian ants.
PMID- 29950755
TI - Transcatheter Aortic Valve Implantation - History, Current Guidelines and
Implications for the Future.
AB - Degenerative aortic stenosis is a disease of the elderly and of growing
importance in an ageing population. Due to the impaired life-expectancy of
patients with symptomatic aortic stenosis, valve replacement should be performed.
Surgical aortic valve replacement is the gold standard treatment; however, median
sternotomy and use of extracorporal circulation is a risk for elderly patients
with comorbidities. The introduction of transcatheter aortic valve implantation
(TAVI) into clinical practice has revolutionized treatment of aortic stenosis in
elderly patients. In most patients, TAVI can be performed through the groin
vessels using local anaesthesia. Most patients fully recover within a few days.
Current debate focuses on whether TAVI should also be used to treat younger
patients as data on long-term durability of these valves is insufficient and
there is a remaining risk of paravalvular leackage.
PMID- 29950756
TI - The sensitivity and specificity of the Falls Efficacy Scale and the Activities
specific Balance Confidence Scale for hemiplegic stroke patients.
AB - [Purpose] This study attempted to investigate the sensitivity and specificity of
the Falls Efficacy Scale (FES) and the Activities-Specific Balance Confidence
Scale (ABC) for community residents with hemiplegic stroke. [Subjects and
Methods] The FES and the ABC data were collected for a sample of 99 community
dwelling hemiplegic stroke patients in Korea. The Receiver Operating
Characteristic (ROC) curve was used to determine the cut-off values, and the area
under the curve (AUC) was used to assess the overall accuracy of each balance
test. Multivariate logistic regression analysis was employed to identify the
predictors of falling. [Results] The cut-off value was 63.75 in the ABC and 66.50
in the FES. The sensitivity and specificity of the ABC was 41.3% and 92.0%,
respectively. The sensitivity and specificity of the FES was 69.8% and 63.9%,
respectively. The AUC was 0.691 for the ABC and 0.678 for the FES. The ABC
explained 28.0% of the variance in the experience of falls. [Conclusion] The ABC
has the ability to determine non-fallers, and it was a good explanatory factor of
experience of falls.
PMID- 29950757
TI - Effects of cognitive loading on lumbar flexion relaxation phenomenon in healthy
people.
AB - [Purpose] The objective of this research was to examine the impact of cognitive
load on the flexion relaxation phenomenon (FRP) during trunk flexion and return
from flexion task. [Subjects and Methods] Twenty-two healthy subjects (18 males,
4 females) participated in the study. Each participant was exposed to 3
experimental conditions: no cognitive task, easy cognitive task and difficult
cognitive task. Surface electromyography was used to measure lumbar erector
spinae muscles activity level. Flexion relaxation ratio (FRR) was compared in
order to assess the differences between the three experimental conditions during
flexion and extension (FLX FRR and EXT FRR). [Results] The FRR was decreased with
increase in cognitive difficulty; the difficult cognitive task was associated
with significant lower value of FLX FRR in both sides. However, these changes
were not significant in easy cognitive task. In addition, the EXT FRR was
decreased in cognitive task conditions, but these results were not statistically
significant except for difficult cognitive task condition in comparison to no
cognitive task condition in left side. [Conclusion] These findings suggest that
cognitive loading can affect FRP in healthy subjects.
PMID- 29950758
TI - Efficacy of subcutaneous lidocaine injection in venous insufficiency: a
prospective, randomized, controlled study, and new treatment protocol.
AB - [Purpose] The purpose of this study was to evaluate the efficacy of subcutaneous
injection with lidocaine in patients with chronic venous insufficiency in the
early stage. [Subjects and Methods] Patients (n=50) randomized to the treatment
group received subcutaneous injections from a mixture of physiological saline
sterile solution and lidocaine once a week to both legs below the knee for 5
sessions. Patients in the treatment group were also given ankle pumping exercises
and compression stockings throughout the treatment. Patients randomized to the
control group (n=50) received only ankle pumping exercises and compression
stockings. Patients were evaluated using the visual analog scale (VAS) for pain
and Chronic Venous Disease Quality of life Questionnaire (CIVIQ-20) for quality
of-life at months 1, 3, 6, at the end of month 12, and at the end of the
injection treatment for 5 sessions. [Results] CIVIQ-20 and VAS results were
significantly lower in the treatment group, than in the control group at months
1, 3 and 6. However, CIVIQ-20 and VAS results were not significantly different,
compared with the pre-operative period at month 12. [Conclusion] We observed that
5-week subcutaneous lidocaine injection treatment was effective in patients who
do not respond to oral medical treatment or in whom surgery is not considered.
PMID- 29950759
TI - Relationship between asymmetric trunk flexion movement and elector spinae muscle
activity.
AB - [Purpose] To clarify the relationship between asymmetric trunk flexion movement
and erector spinae (ES) muscle activity using a three-dimensional motion analysis
system and surface electromyography. [Subjects and Methods] The subjects
comprised 14 healthy individuals. Angles of trunk flexion, rotation, and side
bending were measured using a three-dimensional motion analysis system attached
to the trunk and pelvic segment. Activities of the ES muscle on both sides at the
L1 and L4 levels were measured using surface electromyography. [Results] In
healthy individuals, the ES was more markedly activated in the trunk extension
phase than in the trunk flexion phase. There was no significant difference in
terms of the extent of trunk rotation and trunk side bending during these tasks.
[Conclusion] This study did not clarify the relationship between asymmetric
movement during trunk flexion and ES activity.
PMID- 29950760
TI - Effect of body weight support on predicted locomotive physical activity.
AB - [Purpose] This study aimed to evaluate the effect of body weight support with an
assistive device on predicted locomotive physical activity measured using
triaxial accelerometers in healthy young subjects. [Subjects and Methods] Sixteen
healthy subjects aged 21.9 +/- 1.1 years walked on a treadmill at speeds of 45
and 55 meters/min under 0%, 10%, 20%, and 30% body weight support conditions.
Predicted metabolic equivalents and number of steps were evaluated using triaxial
accelerometers. Measured metabolic equivalents and number of steps were evaluated
using a metabolic system and observers, respectively. Raw data of synthetic
accelerations were also obtained. [Results] Predicted metabolic equivalents and
number of steps and raw data of synthetic accelerations decreased with increasing
amounts of body weight support. [Conclusion] These findings suggest that
accelerometers may underestimate locomotive physical activity with increasing
amounts of body weight support using assistive devices. Thus, it is important to
consider the amount of body weight support when assessing physical activities in
subjects using assistive devices for mobility.
PMID- 29950761
TI - Development of a statistical model for predicting seat pressure felt level in
simulated condition based on direct and anthropometric measurement.
AB - [Purpose] The purpose of this study was to investigate the effects of seat
pressure distribution measurements based on a specific posture to predict the
pressure felt level when seated. [Subjects and Methods] To examine the
relationship between body pressure data and the driver's perception, eleven
subjects were selected to participate in a simulated driving experiment using a
pressure mat as a direct measurement method to measure the seat pan's pressure
distribution. The buttock-popliteal length was measured using an anthropometer,
and the pressure felt ratings evaluated after the body pressure measurements were
recorded. Accordingly, this was then followed by performing statistical analysis
using seat pressure measurements, and the buttock-popliteal length as independent
variables along with subjective ratings selected of the pressure felt by the
drivers' as dependent variables. [Results] The findings of this study suggest
that the direct measurements and anthropometric body data are positively
correlated with the predictive model thereby confirming the validity of the model
with an R2 value of 0.952. [Conclusion] The proposed model is expected to provide
a useful reference value for new vehicle drivers by providing the pressure felt
level based on direct and body measurements in a specific posture.
PMID- 29950762
TI - Awareness of ergonomics & work-related musculoskeletal disorders among dental
professionals and students in Riyadh, Saudi Arabia.
AB - [Purpose] The present research was undertaken to investigate the awareness of
ergonomics and prevalence of musculoskeletal disorders among dental professionals
and students in Riyadh, Saudi Arabia and to find a mean to decrease the
prevalence of musculoskeletal disorders in the future. [Subjects and Methods] A
self-administered survey was prepared and disseminated to dental professionals
and students in Riyadh, Saudi Arabia. The questionnaire was focused on the
awareness of ergonomics and musculoskeletal disorders. Five hundred and sixty-one
participants were included in this survey. [Results] Within the present study,
significant differences were noticed among specialists, general practitioners and
undergraduate students. Work load (risk factors) had great influence on
musculoskeletal disorders in all dental practitioners, and lower back pain was
the most common reported disorder among all practitioners. [Conclusion] Most of
the respondent dentists seem to work in conditions that aggravate disorders of
the musculoskeletal system, the increased prophylactic remedies were directly
associated with the increase of the musculoskeletal disorders symptoms. All
dentists regardless of their dental specialties, are recommended to apply
principles of ergonomics in their daily practice. Moreover, dental ergonomics
should be taught to undergraduate students and strictly implemented in the
clinics to provide comfortable working environment for all dental professionals.
PMID- 29950763
TI - Efficacy of dietary supplement with nutraceutical composed combined with
extremely-low-frequency electromagnetic fields in carpal tunnel syndrome.
AB - [Purpose] The aim of this study was to investigate the clinical effects of a
nutraceutical composed (Xinepa(r)) combined with extremely-low-frequency
electromagnetic fields in the carpal tunnel syndrome. [Subjects and Methods]
Thirty-one patients with carpal tunnel syndrome were randomized into group 1-A
(N=16) (nutraceutical + extremely-low-frequency electromagnetic fields) and group
2-C (n=15) (placebo + extremely-low-frequency electromagnetic fields). The
dietary supplement with nutraceutical was twice daily for one month in the 1-A
group and both groups received extremely-low-frequency electromagnetic fields at
the level of the carpal tunnel 3 times per week for 12 sessions. The Visual
Analogue Scale for pain, the Symptoms Severity Scale and Functional Severity
Scale of the Boston Carpal Tunnel Questionnaire were used at pre-treatment (T0),
after the end of treatment (T1) and at 3 months post-treatment (T2). [Results] At
T1 and T2 were not significant differences in outcome measures between the two
groups. In group 1-A a significant improvement in the scales were observed at T1
and T2. In group 2-C it was observed only at T1. [Conclusion] Significant
clinical effects from pre-treatment to the end of treatment were shown in both
groups. Only in group 1-A they were maintained at 3 months post-treatment.
PMID- 29950764
TI - The importance of a multidisciplinary team and the conditioning services in elite
clubs of roller hockey.
AB - [Purpose] This study describes and compares the conditioning services of the
roller hockey teams of the two most important leagues in Spain: the OK Liga and
the First Division. [Subjects and Methods] A survey was administered to the
people responsible for physical preparation. The response rate was 93%. [Results]
75% of the OK Liga teams have hired someone full time exclusively for training,
with a university degree. The percentage was significantly lower in the First
Division, at a 43.7%. A low percentage of the physical trainers continued with
their academic training, and the consultation of scientific journals. The main
deficiencies are associated with the strength training equipment and facilities.
In the First Division teams, significant deficiencies were found in most of the
variables associated with the training environment. These results show
significant deficiencies in the conditioning services offered by the teams to
their players, especially in non-professional and lower performance level teams.
[Conclusion] Spanish physical trainers should take advantage of advances in
scientific knowledge in the area of conditioning by studying Masters and
consulting scientific journals. The clubs directors and/or coaches should be
aware of the importance of conditioning to improve the training environment. Both
aspects would offer a better training and rehabilitation procedure in the club.
PMID- 29950765
TI - Association between computer-based testing and national examination results among
physical therapy students.
AB - [Purpose] This study examines the relationship between the results of computer
based testing (CBT) and level of satisfaction with learning, school life,
graduation research, and national examination results among freshman and
sophomore undergraduate physical therapy students. [Subjects and Methods] The
subjects of this survey were 56 male and 42 female physical therapy students who
graduated from the International University of Health and Welfare, Ohtawara, in
March 2017. The students were ranked according to four 25th-percentile groups
based on the results of CBT, which was conducted at the end of freshman and
sophomore years. A visual analog scale was used to assess satisfaction levels at
the end of sophomore, junior, and senior years. The results of the national
examination were scored independently. [Results] Compared with the freshman-year
CBT results, we found a significant difference in learning satisfaction during
the senior year and in the national examination. In addition, compared with the
sophomore-year CBT results, there was a significant difference in learning
satisfaction for sophomore, junior, and senior years, as well as in the national
examination. [Conclusion] We found a link between the CBT results from freshman
and sophomore years and those from the national examination. The results suggest
that CBT has an educational effect.
PMID- 29950766
TI - Relationship between the change in one-leg standing time due to visual
information interception and hip joint internal rotation pattern.
AB - [Purpose] To clarify the relationship between the laterality of one-leg standing
time (OLST) due to blocking of visual information and the laterality of hip
internal rotation (IR) range of motion (ROM). [Subjects and Methods] The study
included 101 young healthy male and female students. Hip IR ROM was classified
into three patterns using left and right differences. Regarding OLST, differences
between the left and right measured values with eyes open and closed were
classified into three patterns. The matching rate between hip IR ROM laterality
pattern and OLST laterality pattern was examined with eyes open and closed. The
matching rate of the OLST laterality pattern with hip IR ROM laterality pattern
in an imbalanced group was examined. [Results] A significant difference was
observed between eyes open and closed conditions in the matching rates of OLST
and Hip IR ROM laterality patterns in the imbalanced group. In the imbalanced
group, the pattern on the side where the Hip IR is greater changes to coincide
with the pattern on the side where the OLST is longer, under the eyes closed
condition. [Conclusion] OLST on the side of greater Hip IR ROM tends to be longer
due to visual information interception.
PMID- 29950767
TI - Recognition of roles of various professionals by home-visiting specialists.
AB - [Purpose] To support home care patients through specialist teams, it is important
that home-visiting specialists recognize the roles of other professionals. The
present study aimed to determine whether home-visiting specialists recognized the
roles of various other professionals. [Subjects and Methods] The study population
comprised 400 nurses, 400 rehabilitation specialists, and 122 managerial
dieticians providing home medical care. A questionnaire examining whether the
home-visiting specialists recognize the roles of various other professionals was
mailed to the participants. Returned questionnaires indicated agreement for
participation in this study. Based on the responses to the questionnaire, 49
nurses (response rate: 12.3%), 74 rehabilitation specialists (18.5%), and 42
managerial dieticians (34.4%) were included in the study. [Results] Among all the
professionals, the recognition of roles of their own profession was greater than
that of other professions, as indicated by their response to the question "to
explain possible changes in symptoms and how to deal with possible changes in
symptoms." Unlike in case of other professionals, role recognition among
managerial dieticians was less than 70% for all items. [Conclusion] Home medical
care teams do not always comprise the most suitable professionals. An
understanding of how to compensate for gaps in professional roles is therefore
important. Good physical assessment skills and an understanding of symptoms of
various disorders is important, regardless of the profession.
PMID- 29950768
TI - Effect of scapular stabilization exercise on neck alignment and muscle activity
in patients with forward head posture.
AB - [Purpose] The purpose of this study was to investigate the effects of scapula
movement on neck alignment and the muscles in patients with forward head posture,
who has the structural changes around the neck caused from the forward head
posture, when scapular stabilization exercise is applied. [Subjects and Methods]
A sample of 30 patients with forward head posture were recruited and participated
in an intervention for 30 minutes a day, three times per week for 4 weeks.
Fifteen patients were assigned to the scapular stabilization exercise group and
the remaining 15 were assigned to the neck stabilization exercise group. Before
the intervention, the craniovertebral angle (CVA), cranial rotation angle (CRA),
and muscle activity of the muscles around the neck were measured. Four weeks
later, these 3 factors were re-measured and analyzed. [Results] Within-group
changes in CVA and CRA were observed in both groups and were statistically
significant. Only the CVA group had a statistically significant between-group
differences. Within-group changes in muscular activity were significant
differences in all groups. Between groups, the lower back trapezius and serratus
anterior showed statistically significant differences. [Conclusion] Scapular
stabilization brought about improvement in posture through activation of the neck
muscles, the lower trapezius, and the serratus anterior. Therefore, the
intervention has a positive effect on neck alignment by reducing the compensatory
movements of the muscles involved in forward head posture. Structural changes are
observed.
PMID- 29950769
TI - Relationship between white matter fiber damage and revised version of the ability
for basic movement scale in patients with stroke: a diffusion tensor tract-based
spatial statistic study.
AB - [Purpose] To clarify the relationship between white matter fiber damage and the
Ability for Basic Movement Scale (ABMS) II in patients with stroke in a diffusion
tensor tract-based spatial statistic study. [Subjects and Methods] Twelve
patients with stroke (seven men and five women, mean age +/- SD: 61.6 +/- 8.5
years) were evaluated using the ABMS II. The patients were divided into the ABMS
II good group and the ABMS II poor group. Tract-based spatial statistical
analysis was performed using diffusion tensor images in both groups. [Results]
Patients in the ABMS II good group had significantly higher fractional anisotropy
values of the anterior thalamic radiation (ATR), superior longitudinal fasciculus
(SLF), inferior occipitofrontal fasciculus (IOF), and uncinate fasciculus (UF) of
the lesion-containing hemisphere than patients in the ABMS II poor group.
[Conclusion] ATR, SLF, and IOF damage may affect ABMS II scores in patients with
stroke.
PMID- 29950770
TI - Effects of trunk stabilization exercise on the local muscle activity and balance
ability of normal subjects.
AB - [Purpose] The purpose of this study was to investigate the effects of trunk
stabilization exercise on the transvers abdominalis (TA) and internal oblique
(IO) muscle activity and balance ability of normal subjects. [Subjects and
Methods] Forty healthy male subjects without orthopedic history of the lower
extremity were selected for the present study. The experimental group received a
hollowing exercise, curl-up and bridging exercise. The control group received a
pelvic tilting exercise in the sitting position for the same period of time.
[Results] Significant differences in the post-training gains in Balance index,
TA, IO were observed between the experimental group and the control group.
[Conclusion] The trunk stabilization exercise improved the balance ability and
increased the activity of the TA and IO muscle.
PMID- 29950771
TI - Effects of integrated treatment with LED and microcurrent on muscle tone and
stiffness in the calf muscle during moderate aerobic exercise.
AB - [Purpose] This study aimed to investigate the effects of the therapeutic device
combined with LED and microcurrent (MC) on muscle tone and stiffness in the calf
muscle after its application during moderate aerobic exercise. [Subjects and
Methods] Twenty healthy adult subjects were randomized to either the test group
of the therapeutic device combined with LED and MC or the control group, and they
walked on a 10%-sloped treadmill with a 5 km/hr speed for 30 minutes. Each of the
subjects in the test group performed treadmill exercise with the therapeutic
device attached to the edge of his or her calf muscle. After the exercise, the
muscle tone and stiffness at the edge of the calf muscle were measured. [Results]
With respect to the muscle tone, a statistically significant difference was found
between the two groups only 5 minutes after the exercise. Concerning muscle
stiffness, significant differences were shown between the two groups right after
the exercise and 5 minutes after the exercise. [Conclusion] Integrated treatment
with LED and MC on is considered helpful for lowering the muscle tone 5 minutes
after the exercise, and for lowering the muscle stiffness right after the
exercise and 5 minutes after the exercise.
PMID- 29950772
TI - Changes in ventilation mechanics during expiratory rib cage compression in
healthy males.
AB - [Purpose] The purpose of this study was to clarify the differences in ventilation
mechanics between quiet breathing and expiratory rib cage compression, and
between expiratory rib cage compression on the upper rib cage and on the lower
rib cage. [Subjects and Methods] Subjects comprised 6 healthy males. Expiratory
rib cage compression was performed manually by compressing the upper and lower
rib cages. Changes in the lung volume, flow rate, and esophageal and gastric
pressure were examined. [Results] The end expiratory lung volume was
significantly lower during expiratory rib cage compression than at rest, but the
end inspiratory lung volume was not significantly different. When compared with
the esophageal and gastric pressures on the upper and lower rib cages at rest,
the gastric pressures were significantly higher at end expiration. Lung
resistance was significantly higher during expiratory rib cage compression than
at rest. [Conclusion] Although expiratory rib cage compression promoted
expiration and increased tidal volume, the lung volume did not increase beyond
end inspiratory levels at rest. Lung resistance may increase during expiratory
rib cage compression due to a decrease in lung volume. The mechanism by which
expiration is promoted differed between the upper and lower rib cages.
PMID- 29950773
TI - Pelvic floor muscle training and electrical stimulation as rehabilitation after
radical prostatectomy: a randomized controlled trial.
AB - [Purpose] To investigate the effect of electrical stimulation and pelvic floor
muscle training on muscle strength, urinary incontinence and erectile function in
men with prostate cancer treated by radical prostatectomy. [Subjects and Methods]
One hundred twenty-three males were randomized into 3 groups 1 month after RP:
(G1, n=40) control; (G2, n=41) guideline: patients were instructed to perform
three types of home exercises to strengthen the pelvic floor and (G3, n=42)
electrical stimulation: patients in this group were also instructed to perform
exercises as group G2, and also received anal electro-stimulation therapy, twice
a week for 7 weeks. The primary outcome assessment was based on the measurement
of the recovery of pelvic floor muscle strength between groups. Secondary
outcomes were: 1 hour Pad Test, ICIQ-SF, IIEF-5 and IPSS. Data were obtained
preoperatively and at 1, 3 and 6 months after surgery. [Results] There was no
significant difference in the demographic data among groups. Greater urinary
leakage and pelvic floor muscle weakness in the first month compared to pre
treatment improved after 3 and 6 months postoperative, without difference among
groups. [Conclusion] The muscle strength recovery occurs independently of the
therapy employed. Pelvic floor exercises or electrical stimulation also did not
have an impact on the recovery of urinary continence and erectile function in our
study.
PMID- 29950774
TI - Effects of active vibration exercise using a Flexi-Bar on balance and gait in
patients with chronic stroke.
AB - [Purpose] This study aimed to investigate the effect of active vibration exercise
using a Flexi-Bar on the balance and gait of chronic stroke patients. [Subjects
and Methods] Twenty-two patients with chronic stroke were randomly assigned to an
experimental or control group (n=11 each). The experimental group performed
active vibration exercise using a Flexi-Bar. Balance was measured using the Berg
Balance Scale and Functional Reach Test. Gait was measured with the 10-meter Walk
Test and Timed Up and Go Test. [Results] Intragroup comparisons in the
experimental group showed significant differences in Berg Balance Scale,
Functional Reach Test, 10-meter Walk Test, and Timed Up and Go Test results,
whereas intergroup comparisons showed significant differences in Berg Balance
Scale, Functional test, 10-meter Walk Test, and TUGT results. [Conclusion] On the
basis of these results, it was concluded that active vibration exercise using a
Flexi-Bar effectively improves the balance and gait of patients with chronic
stroke.
PMID- 29950775
TI - The test-retest reliability and minimal detectable change of the short-form
Barthel Index (5 items) and its associations with chronic stroke-specific
impairments.
AB - [Purpose] To establish the test-retest reliabilities, minimal detectable change
of the Short form Barthel Index and associations with stroke-specific
impairments. [Subjects and Methods] The Short form-Barthel Index assessment was
tested on 24 chronic stroke patients twice, 7 days apart. A relative reliability
index (ICC2,1), Weighted Kappa Coefficients was used to examine the level of
agreement of test-retest reliability for SF-BI, Absolute reliability indices,
including the standard error of measurement and the minimal detectable change.
The validity was demonstrated by spearman correlation of SF BI-total score with
Postural Assessment Scale for Storke, Fugl Meyer Assessment. [Results] There was
excellent agreement between test-retest for individual items of BI and total
score ICC2,1=0.91 and it all showed acceptable SEM and MDC were 2.83 score, 7.84
score respectively. The item-to-total correlations were all significant, ranging
from r=0.83-0.92. SF-BI showed good internal consistency. Individual items also
possessed high internal consistency 0.82-0.86. The SF-BI and total score were
demonstrated high concurrent validity with the PASS, FMA. [Conclusion] This study
has demonstrated that the SF-BI is a useful instrument with high test-retest
reliability, Absolute reliability indices, internal consistency and validity.
PMID- 29950776
TI - Effect of a cervical support pillow on sternocleidomastoid activity and
satisfaction in asymptomatic participants.
AB - [Purpose] The aim of this study was to examine the changes in sternocleidomastoid
muscle (SCM) activity when using a cervical support pillow (CSP) and to determine
the pillow's effect on satisfaction in asymptomatic participants. [Subjects and
Methods] This study followed a cross-over design and the order of the
measurements was counterbalanced. Twenty asymptomatic participants were
positioned supine for 5 minutes by using either a CSP or a general pillow (GP)
while the activity of the SCM was measured using surface electromyography.
[Results] The CSP significantly decreased the activity of the SCM compared with
the GP, and satisfaction after use of the CSP was significantly greater than that
after use of the GP. [Conclusion] This study suggests that the CSP may be
effective in preventing unnecessary neck muscle activation during sleep in
asymptomatic people.
PMID- 29950777
TI - Hypermobile Ehlers-Danlos syndrome and rehabilitation: taking stock of evidence
based medicine: a systematic review of the literature.
AB - [Purpose] The aim of the study was to conduct a systematic review about
rehabilitation treatment of hypermobile Ehlers-Danlos syndrome, according to
Evidence Based Medicine. [Methods] A systematic search has been conducted in
following database: PubMed, PEDro, Cochrane, EDS Base Index, TRIP and CINHAL; no
time restrictions were adopted. PICO method was employed to formulate the
clinical query. Hypermobile Ehlers-Danlos syndrome and physiotherapy were the
main keywords of the research. [Results] 1,869 articles emerged from the primary
search. After duplicates removal, 1,709 papers have been screened by title and
abstracts and then 1,698 were excluded following the inclusion criteria. 11
papers have been admitted to the last stage of the review and have been evaluated
in their full-text version. Only one cohort study met the review's final step
selection criteria. One cohort study on the efficacy of an integrated
physiotherapeutic and cognitive behavioural treatment was evaluated by means of
Newcastle-Ottawa Quality Assessment score and resulted of poor evidence.
[Conclusion] At the present time, there is no Evidence Based Medicine literature
on hypermobile Helers-Danlos syndrome rehabilitation. Clinical studies with high
level of evidence are necessary in order to assess the efficacy of
physiotherapeutic approaches.
PMID- 29950778
TI - Case study of continuous knee joint traction treatment on the pain and quality of
life of patients with degenerative gonarthritis.
AB - [Purpose] The purpose of this study was to examine the effects of continuous knee
joint traction treatment on the pain and quality of life of patients with
degenerative gonarthritis. [Subjects and Methods] Continuous knee joint traction
treatment was administered to 59 year-old man and 62 year-old woman diagnosed
with degenerative gonarthritis for 20 minutes, once a day, five times a week for
4 weeks. Pain and quality of life were measured using the visual analogue scale
(VAS) and the short form 36-item health survey (SF-36), respectively. [Results]
The VAS score of the male patient before treatment was 8 points but it decreased
to 1 point after treatment, and SF-36 score increased from 81 points before
treatment to 93 points after treatment. In addition, the VAS score of the 62 year
old female patient was 7 points before treatment but it decreased to 2 points
after treatment, and SF-36 score increased from 78 points before treatment to 96
points after treatment. [Conclusion] The purpose of the study was to report 2
cases of patients with degenerative gonarthritis of the knee who received
continuous knee joint traction.
PMID- 29950779
TI - Correlation between isometric shoulder strength and racket velocity during
badminton forehand smash movements: study of valid clinical assessment methods.
AB - [Purpose] The purpose of this study was to confirm the correlation between racket
velocity during the forehand smash movements with shoulder extensor strength and
internal rotator strength in the neutral and abducted positions. [Subjects and
Methods] Fourteen collegiate badminton players participated in the study.
Measurements were performed shoulder strength, using torque calculated from the
upper extremity length and the isometric force, and racket velocity during the
forehand smash movements. The shoulder extensor strength and internal rotator
strength were measured in the neutral and abducted positions. [Results] The
extension torque and internal rotation torque of the shoulder in the neutral
position were not significantly correlated with racket velocity. Additionally,
correlations between extension torque of the shoulder in the maximum abducted
position and racket velocity were insignificant. However, the internal rotation
torque of the shoulder in the abducted external rotated position was
significantly correlated with racket velocity (r=0.652). [Conclusion] The
shoulder internal rotator strength in the abducted external rotated position are
suitable measurements for evaluating badminton players.
PMID- 29950780
TI - Gender and posture are significant risk factors to musculoskeletal symptoms
during touchscreen tablet computer use.
AB - [Purpose] To investigate the prevalence of neck and shoulder symptoms during the
use of tablet computer, and to identify the risk factors associated with these
symptoms. [Subjects and Methods] A cross-sectional survey was conducted to study
tablet computer usage, posture during use, and neck and shoulder symptoms in 412
participants in a school setting. Significant risk factors for musculoskeletal
symptoms during tablet computer use were identified. [Results] Overall prevalence
of musculoskeletal symptoms during tablet computer use was 67.9% with greater
prevalence of neck symptoms (neck: 84.6%; shoulder/upper extremity: 65.4%).
Significant risk factors associated with symptoms during use were: current
musculoskeletal symptoms, gender, roles, and postural factors including: sitting
without back support, sitting with device in lap, and lying on the side and on
the back during tablet computer use. A multivariate analysis further showed that
the odds for females to have symptoms were 2.059 times higher than males.
[Conclusion] The findings revealed that female gender and other postural factors
were significantly associated with musculoskeletal symptoms during the use of
tablet computer. Among all postural factors, sitting without back support was
identified as the most important risk factor for having musculoskeletal symptoms.
PMID- 29950781
TI - Effects on muscle activities according to the type of bodyblade exercise in
quadruped position.
AB - [Purpose] Most studies on bodyblade exercise have examined changes in muscle
activities in the trunk and shoulders according to the hand position or direction
while in a standing position. The present study compared and examined the changes
in muscle activities around the shoulders and trunk according to different
bodyblade lifting methods during stabilization exercise in a quadruped position.
[Subjects and Methods] The present study was conducted on 20 healthy males. The
following exercise four types were performed with the bodyblade held by flexing
the dominant arm at 180 degrees in a quadruped position. The muscle activity and
the ratio of muscle activity were measured. [Results] The SA and IO, EO muscles
showed significant differences. Moreover, the SA/UT activity ratio showed
significant differences according to the type of exercise. The Tukey's post hoc
test results were as follows: for the SA muscle, exercise types 4, 2 were more
effective than types 1, 3: and for the IO muscle, types 1, 2 were more effective
than types 3, 4. [Conclusion] The present study showed that type 2 scapular
stabilization exercise (crossed leg lifting with the hand raised above the head
on a vertical plane) showed selective and positive effects on trunk muscle
strengthening and stabilization. In future, additional studies are required to
design effective exercise programs for pain management and improvement of muscle
activities in patients with complaints of shoulder pain due to scapular winging.
PMID- 29950782
TI - Occupation-based differences in shared perceptions of older resident needs within
multidisciplinary care teams: a cross-sectional study of care workers, nurses,
and therapists linked to older residents.
AB - [Purpose] To examine whether the needs of older individuals are commonly
understood by multidisciplinary team members at elderly care facilities.
[Subjects and Methods] A questionnaire survey with care workers, nurses, and
therapists linked to residents and structured interviews with residents were
conducted at eight facilities in Japan. The questionnaire comprised 25 items
regarding basic activities of daily living, instrumental activities of daily
living (IADL), environment and lifestyle (EL), and emotion. [Results] The data of
88 residents (83.0% female, 86.4% aged >=75 years) and 125 staff members (63 care
workers, 36 nurses, and 26 therapists) were analyzed. Perceptions regarding the
subjective needs of residents differed significantly by occupation with regard to
pace of eating, pace of dressing, and freedom to brush at any time; shaving or
putting on make-up; personal space, role performance, and health exercises; and
feeling good. All three occupations underestimated the subjective needs of
residents for household chores. [Conclusion] Staff members had insufficient
understanding of the subjective needs of residents, with a tendency to
underestimate IADL and EL needs. Perceived subjective needs also differed by
occupation. Sharing the understanding of subjective needs of older individuals
within multidisciplinary care teams is desired.
PMID- 29950783
TI - A randomized, double-blind study to assess if vitamin D treatment affects the
outcomes of rehabilitation and balance in hemiplegic patients.
AB - [Purpose] To investigate the effect of vitamin D supplementation on
rehabilitation outcomes and balance in patients having hemiplegia due to ischemic
stroke. [Subjects and Methods] Vitamin D levels of 132 patients hospitalized for
hemiplegia rehabilitation due to ischemic stroke were tested. Consequently,
86/132 patients had low vitamin D levels, 72 of which met the inclusion criteria
and were included in the study. Patients were divided into two groups: Group A
(injected with 300,000 IU vitamin D), and Group B (injected intramuscularly with
saline). Each patient was tested at the baseline and at the third month using the
Brunnstrom recovery staging, functional ambulation scale, modified Barthel index,
and Berg balance scale. The findings were compared between the groups. [Results]
By the end of the third month, The Berg balance scale results and modified
Barthel index scores significantly differed between the two groups, whereas
Brunnstrom recovery staging and functional ambulation scale test results did not.
[Conclusion] This study found that vitamin D administration increased the
activity levels and accelerated balance recovery but did not significantly affect
ambulation or motor recovery. These results warrant confirmation by longer follow
up studies with a larger number of participants.
PMID- 29950784
TI - Effects of task velocity and center of mass acceleration during Y-Balance Test in
elderly females with good and poor visual acuity.
AB - [Purpose] To explore the effects of good binocular visual acuity (BVA) compared
to poor BVA, reach distance, task velocity, and center of mass (COM) acceleration
were evaluated in elderly females performing the Y-Balance Test (YBT) using a
cross-sectional design. [Subjects and Methods] A total of 13 participants had BVA
of >=0.4 log of the minimum angle of resolution (logMAR) (poor BVA group), and
the other 13 had BVA of <=0.3 logMAR (good BVA group). An accelerometer was
attached over participants' L3 spinous process, and they then performed the YBT.
[Results] The normalized reach distances in the three directions among the good
BVA group were longer than those among the poor BVA group. The task velocity in
the good BVA group was significantly higher, whereas COM acceleration in the A
direction was significantly lower compared with the poor BVA group. [Conclusion]
Visual status must be considered when older adult individuals undergo physical
therapy and functional training to ensure that healthcare professionals can
better assist older adult women.
PMID- 29950785
TI - The awareness of healthcare staff towards post-stroke cognitive impairment: a
cross sectional study.
AB - [Purpose] This study aimed to determine the awareness amongst healthcare staff of
post-stroke cognitive impairment in a university teaching hospital and supporting
stroke rehabilitation unit. [Subjects and Methods] A cross sectional study was
employed to collect data from 20 healthcare staff about post-stroke cognitive
impairment. This study was conducted in Ireland at two sites, the Acute Stroke
unit in Cork University Hospital, and the Stroke Rehabilitation unit and
Assessment and Treatment Centre in St. Finbarr's Hospital. [Results]
Approximately 75% of participants felt that they had knowledge about post-stroke
cognitive deficits, with around 50% of them having patients with persistent
cognitive decline between 40% and 60%. Most participants (70%) agreed that
cognitive function should be routinely assessed and the majority (85%) discussed
the potential impact of post-stroke cognitive deficits with patients and their
families. However, some participants need to be aware of post-stroke cognitive
deterioration. [Conclusion] Although there was evidence of good practice, a small
number of healthcare staff felt that they did not have sufficient knowledge about
post-stroke cognitive deficits. Thus, further professional education should be
provided to improve the knowledge of healthcare staff about potential cognitive
impairments after stroke.
PMID- 29950786
TI - The relationship between isokinetic strength and functional performance tests in
patients with knee osteoarthritis.
AB - [Purpose] The main purpose of the study was to examine the relationship of a
battery of frequently used functional assessment tests with quadriceps and
hamstrings isokinetic strength in Knee-osteoarthritis (OA) patients. Secondarily,
the predictability of isokinetic strength on these performance variables was also
assessed. [Subjects and Methods] Seventeen males and 23 females with Knee-OA,
were assessed via a) the common functional tests: 6-minute walk test, Timed up
and-go test, 30-second chair test and 12-stair test and b) isokinetic concentric
extension-flexion at 120 degrees /s and 180 degrees /s. [Results] Both Knee
Extension and Flexion Peak Torque per Body weight showed moderate to strong,
statistically significant correlation, with all 4-functional performance tests,
for both velocities. Both 12-stair test and 30-second chair test were significant
predictors in all analyses, while the 6-minute walk test was an additional
significant predictor of the 120 degrees /s knee flexion. [Conclusion] Thigh
muscle strength in both tested velocities proved to be significantly correlated
with functional performance. The 12-stair test and 30-second chair test results
were significant predictors for isokinetic extension and flexion in both
velocities. It appears that those two tests challenge the knee and the
surrounding musculature in a manner that reflects muscle strength.
PMID- 29950787
TI - The effect of trunk stabilization circuit exercise using a rubber mat on the
thickness and white area index of transverse abdominis in healthy young adults.
AB - [Purpose] The purpose of this study was to investigate the effect of trunk
stabilization circuit exercise using a rubber mat on the thickness and white area
index of the transverse abdominis in college students in their 20's. [Subjects
and Methods] The subjects were randomly assigned to the experimental group and
the control group. Those exercises were provided to twenty eight healthy adults
in their 20s for four weeks and the thickness of transverse abdominis was
measured before study and after 4 weeks. [Results] There were significant
differences in interaction between two groups. Paired t-test for thickness and
white area index of transverse abdominis showed statistically significant
differences to experimentals than controls. Independent t-test for white area
index of transverse abdominis also showed statistically significant differences
to experimentals than controls. [Conclusion] In conclusion, there was
statistically significant difference between the effects of trunk stabilization
circuit exercises on back muscles according to types of the surface, and it is
expected that this result will be used as a basic data in studies of abdominal
muscle stabilization in the future.
PMID- 29950788
TI - Structural damage detection using finite element model updating with evolutionary
algorithms: a survey.
AB - Structural damage identification based on finite element (FE) model updating has
been a research direction of increasing interest over the last decade in the
mechanical, civil, aerospace, etc., engineering fields. Various studies have
addressed direct, sensitivity-based, probabilistic, statistical, and iterative
methods for updating FE models for structural damage identification. In contrast,
evolutionary algorithms (EAs) are a type of modern method for FE model updating.
Structural damage identification using FE model updating by evolutionary
algorithms is an active research focus in progress but lacking a comprehensive
survey. In this situation, this study aims to present a review of critical
aspects of structural damage identification using evolutionary algorithm-based FE
model updating. First, a theoretical background including the structural damage
detection problem and the various types of FE model updating approaches is
illustrated. Second, the various residuals between dynamic characteristics from
FE model and the corresponding physical model, used for constructing the
objective function for tracking damage, are summarized. Third, concerns regarding
the selection of parameters for FE model updating are investigated. Fourth, the
use of evolutionary algorithms to update FE models for damage detection is
examined. Fifth, a case study comparing the applications of two single-objective
EAs and one multi-objective EA for FE model updating-based damage detection is
presented. Finally, possible research directions for utilizing evolutionary
algorithm-based FE model updating to solve damage detection problems are
recommended. This study should help researchers find crucial points for further
exploring theories, methods, and technologies of evolutionary algorithm-based FE
model updating for structural damage detection.
PMID- 29950789
TI - Comparison of long-term results of carotid endarterectomy for asymptomatic
carotid artery stenosis.
AB - This article summarizes the current study situation on treatment of asymptomatic
carotid artery stenosis and discusses the evidence situation in the literature.
The 10-year results of the ACST study have shown that in comparison to
conservative treatment, carotid endarterectomy (CEA) has retained a positive long
term effect on the reduction of all forms of stroke. All multicenter randomized
controlled trials comparing CEA with carotid artery stenting (CAS) and, in
particular the SAPHIRE and CAVATAS studies, have in common that despite a basic
evidence level of Ib, the case numbers of asymptomatic patients are too small for
a conclusive therapy recommendation. In the overall assessment of the CREST study
the resulting difference in the questionable endpoint of "perioperative
myocardial infarction" in favor of the CAS methods, could not be confirmed for
exclusively asymptomatic patients. In the long-term course of the CREST study,
both methods were classified as equivalent, even when the 4-year results of
periprocedural and postprocedural stroke rates in the separate assessment of the
asymptomatic study participants clearly favored the CEA. The results of the ACST
1 study showed an equivalent effect of both treatment methods with respect to all
investigated endpoints; however, the unequal sizes of the groups in addition to
the statistically insufficient case numbers put a question mark on the validity
of the study results. The results of the ASCT-2 and CREST-2 studies are to be
awaited, which also investigate the significance of "CEA versus CAS" (ASCT-2) and
"CEA/CAS + best medical treatment (BMT) versus BMT alone" in only asymptomatic
stenoses. The current S3 guidelines allow operative therapy to be considered in
patients with a 60-99% asymptomatic carotid artery stenosis, because the risk of
stroke is statistically significantly reduced.
PMID- 29950790
TI - Noninvasive measurements of tissue perfusion in critical limb ischemia.
AB - Critical limb ischemia (CLI) remains a challenge for an interdisciplinary
therapeutic team due to chronic nonhealing wounds. Against this background, there
is a necessity of quality control after revascularization. Beside the isolated
evaluation of the macrocirculation by Ankle-Brachial or Toe-Brachial Index
measurements, the microcirculation as an additional important factor of wound
healing often remains underestimated. The following article gives an overview
about the current investigation methods for noninvasive perfusion control of the
CLI patient. Therefore, transcutaneous oxygen pressure (tcpO2), the "oxygen-to
see" method which is a combination of white light tissue spectrometry and laser
Doppler flowmetry, fluorescence angiography with indocyanine green, and
multispectral optoacoustic tomography will be described.
PMID- 29950791
TI - Pathophysiology of chronic limb ischemia.
AB - Chronic ischemia of the lower extremities is an everyday problem in vascular
surgery clinics. In Germany, approximately 3% of all hospitalizations are due to
peripheral artery disease (PAD), with critical limb ischemia (CLI) in particular
showing a rapid increase. The consequences of chronic undersupply range from
reduced walking distance to loss of limbs. At the beginning there are stress
factors, such as hyperlipidemia (LDL), free radicals, arterial hypertension,
infections or subclinical inflammation that interfere with endothelial
homeostasis and cause endothelial dysfunction with increased permeability. Cells
of the immune system are attracted and migrate into the vascular wall, where they
lead to the degradation of matrix components and destabilization of the plaque.
By changing the phenotype of smooth muscle cells and macrophages towards
osteoclast-like cells, bone-like hardening of the vessel wall takes place. Above
a vessel wall thickness of approximately 100 um, hypoxia-induced factor (HIF
1alpha) is intensified by the lack of oxygen, which leads to an increase in
growth factors, such as vascular endothelial growth factor (VEGF). This promotes
angiogenesis, but it is not sufficient to compensate for a stenosed artery.
Arteriogenesis refers to the growth of existing collateral vessels. The driving
forces are the pressure gradient before and after the stenosis and the shear
forces acting on the vessel walls. In the case of progressive stenosis, the
compensatory capacities can be overtaxed and a manifest hypoxia in the tissue
with regression of the obtained vascular structures and tissue atrophy occurs.
PMID- 29950792
TI - Visceral artery aneurysms.
AB - Visceral artery aneurysms are rare with an incidence of only 0.01-0.1% of the
population. Open surgical or endovascular elimination should be performed for
aneurysms greater than 2 cm in size. The risk of aneurysm rupture is then
approximately 25-40%. If the aneurysm ruptures the mortality can be as high as
76%. For mycotic aneurysms or spurious aneurysms there is no lower limit to the
diameter size for the need of treatment. Sudden abdominal pain during pregnancy
can be caused by visceral artery aneurysms and must be further clarified. The
indications for surgery during pregnancy should be made generously. The clinical
symptoms (abdominal complaints) of visceral artery aneurysms are manifold. The
treatment can be either an open surgical approach or endovascular treatment. In
the emergency setting, if endovascular treatment is no longer possible, an open
surgical treatment needs to be performed. There are so far no randomized studies
which could identify one of the procedures (open surgery vs. endovascular
surgery) as clearly being superior. The prognosis after treatment is satisfactory
with a 5-10 year survival rate of approximately 90%.
PMID- 29950793
TI - The incidence of incisional hernia after aortic aneurysm is not higher than after
benign colorectal interventions: A retrospective control-matched cohort study.
AB - Background: Abdominal aortic aneurysms (AAA) have most probably an inflammatory
origin, whereby the elastica is the layer actually involved. In the past,
collagen weackness was supposed to be the shared cause of both, AAA and
incisional hernias. Since the development of new techniques of closure of the
abdominal wall over the last decade, collagen deficency seems to play only a
secondary etiologic role. Objectives: The aim of the study was to investigate
whether the incidence of incisional hernia following laparotomy due to AAA
differs from that of colorectal interventions. Material and methods: This was a
retrospective control matched cohort study. After screening of 403 patients with
colorectal interventions and 96 patients with AAA, 27 and 72 patients,
respectively were included. The match criteria for inclusion of patients with
colorectal interventions were: age, benign underlying disease and median
xiphopubic laparotomy. The primary endpoint was the incidence of an incisional
hernia. The secondary endpoints were the risk profile, length of stay in the
intensive care unit and postoperative complications. Data analysis was carried in
the consecutive collective from 2006 to 2008. Results: In the group with AAA the
mean follow-up was 34.5+/-18.1 months and in the group with colorectal
interventions 35.7+/-21.4 months. The incidence of incisional hernias showed no
significant differences between the two groups. In the AAA group 10 patients
(13.8%) developed an incisional hernia in contrast to 7 patients in the
colorectal intervention group (25.9%). Conclusions: In our collective patients
with AAA did not show an increased incidence of incisional hernia in comparison
to patients with colorectal interventions with comparable size of the laparotomy
access and age. The quality of closure of the abdominal wall seems to be an
important factor for the prevention of incisional hernia.
PMID- 29950794
TI - Complex endovascular treatment of intact aortic aneurysms: An analysis of health
insurance claims data.
AB - Background: The complex endovascular repair of aortic aneurysms and dissections
with fenestrated or branched stent grafts (FB-EVAR) remains challenging for
interventional vascular surgery. To date, the evidence regarding treatment
patterns and outcome measures consists of single center studies; however, it
might be reasonable to validate results with multicenter real-world evidence.
Methods: Health insurance claims data from Germany's third largest insurance
provider, DAK-Gesundheit, were used to determine outcomes following FB-EVAR of
non-ruptured thoracic aorta (TA) or thoracoabdominal including pararenal
abdominal (TAA) aorta. The study included patients operated between January 2008
and April 2017. Results: Included were 984 patients (18.1% female) who underwent
FB-EVAR. Patients with treatment of the TA were younger (71.7 vs. 73.2 years, p <
0.001) and more often female (38.5% vs. 17.0%, p < 0.001) as compared to patients
with treatment of TAA. In the TA group peripheral arterial disease was less
frequent compared to the TAA group (67.3% vs. 80.4%, p = 0.036). Mortality was
significantly (p < 0.001) higher following repair of the TAA compared to the TA
at discharge (17.3% vs. 4.6%), at 30 days (26.9% vs. 8.2%) and at 90 days (34.6%
vs. 10.1%). Patients with treatment of the TAA suffered more often from stroke as
compared to the TA group (7.7% vs. 1.2%, p = 0.002). Conclusion: In this large
scale German analysis of claims data, multicenter real-world evidence was
different from single center studies regarding patient risk-factors and outcome
measures. Validated multicenter registry studies could help to further
investigate this topic in times of increasing procedures.
PMID- 29950795
TI - Quantifying the Interaction between Copper-Zinc Superoxide Dismutase (Sod1) and
its Copper Chaperone (Ccs1).
AB - Immature copper-zinc superoxide dismutase (Sod1) is activated by its copper
chaperone (Ccs1). Ccs1 delivers a single copper ion and catalyzes oxidation of an
intra-subunit disulfide bond within each Sod1 monomer through a mechanistically
ambiguous process. Here, we use residue specific fluorescent labeling of immature
Sod1 to quantitate the thermodynamics of the Sod1*Ccs1 interaction while
determining a more complete view of Ccs1 function. Ccs1 preferentially binds a
completely immature form of Sod1 that is metal deficient and disulfide reduced
(E, E-Sod1SH). However, binding induces structural changes that promote high
affinity zinc binding by the Ccs1-bound Sod1 molecule. This adds further support
to the notion that Ccs1 likely plays dual chaperoning roles during the Sod1
maturation process. Further analysis reveals that in addition to the copper
dependent roles during Sod1 activation, the N- and C-terminal domains of Ccs1
also have synergistic roles in securing both Sod1 recognition and its own active
conformation. These results provide new and measurable analyses of the molecular
determinants guiding Ccs1-mediated Sod1 activation.
PMID- 29950796
TI - Polarization-Dependent SFG Spectroscopy of Near Ambient Pressure CO Adsorption on
Pt(111) and Pd(111) Revisited.
AB - Polarization-dependent sum frequency generation (SFG) vibrational spectroscopy
was employed to examine CO overlayers on Pt(111) and Pd(111) single crystal
surfaces at room temperature. Utilizing different polarization combinations (SSP
and PPP) of the visible and SFG light allows to determine the molecular
orientation (tilt angle) of interface molecules but the analysis of the measured
Ippp/Issp is involved and requires a proper optical interface model. For
CO/Pt(111), the hyperpolarizability ratio R=betaaac/betaccc=betabbc/betaccc is
not exactly known and varying R in the range 0.1-0.5 yields tilt angles of 40
degrees -0 degrees , respectively. Based on the known perpendicular adsorption of
CO on Pt, an exact R-value of 0.49 was determined. Polarization-dependent SFG
spectra in the pressure range 10-4 to 36 mbar did not indicate any change of the
tilt angle of adsorbed CO. Modeling also indicated a strong dependence of
Ippp/Issp on the incidence angles of visible and IR laser beams. Complementing
previous low temperature/low pressure data, room temperature CO adsorption on
Pd(111) was examined from 10-6 to 250 mbar. The absolute PPP and SSP spectral
intensities on Pt and Pd were simulated, as well as the expected Ippp/Issp
ratios. Although CO on Pt and Pd should exhibit similar intensities (at high CO
coverage), the higher Ippp/Issp ratio for Pd (48 vs. 27 on Pt) renders the
detection of adsorbed CO in SSP spectra difficult. The presence or absence of CO
species in SSP spectra can thus not simply be correlated to tilted or
perpendicular CO molecules, respectively. Careful modeling, including not only
molecular and interface properties, but also the experimental configuration
(incidence angles), is certainly required even for seemingly simple adsorbate
substrate systems.
PMID- 29950797
TI - Paraesophageal Hiatal Hernia Repair With Urinary Bladder Matrix Graft.
AB - Background and Objectives: Paraesophageal hiatal hernia repair can be performed
with or without mesh reinforcement. The use, technique, and mesh type remain
controversial because of mixed reports on mesh-related complications. Short-term
outcomes have become important in all forms of surgery. Methods: From January
2012 through April 2017, all patients who underwent isolated hiatal hernia repair
in our center were reviewed. Concomitant bariatric surgery cases were excluded.
Repairs reinforced by porcine urinary bladder matrix (UBM) graft were compared to
non-UBM repairs. Statistical comparison was based on a Wilcoxon 2-sample test or
Fisher's exact test. Results: We reviewed 239 charts; 110 bariatric cases and 8
cases with non-UBM reinforcement were excluded. We identified 121 patients: 56
UBM-reinforced (46.3%) versus 65 non-UBM (53.7%). Sixteen (28.6%) UBM cases were
male versus 23 (35.4%) non-UBM cases. The UBM patients were significantly older
(63.9 versus 54.3; P = .001). There was no difference in mean BMI (29.6 vs 28.5;
P = .28). Cases were performed laparoscopically (60.7% vs 67.7%; P = .45) or
robotically (39.3% vs 32.3%; P = .45), with no conversions to open. The UBM group
had a longer mean operative time (183 minutes vs 139 minutes; P = .001).There was
no difference in median length of stay (2 days vs 2 days; P = .09) or 30-day
readmission rate (7.1% vs 7.5%; P =.99). Postoperative complications were graded
according to the Clavien-Dindo classification, and there was no difference (19.6%
vs 9.2%; P = .12). Conclusions: Hiatal hernia repair with UBM reinforcement can
be performed safely with no increase in postoperative complications.
PMID- 29950798
TI - Optimizing Hospital Resource Utilization in Bariatric Readmission.
AB - Background and Objectives: The prevalence of patients with a history of bariatric
surgery is climbing. Medical and surgical questions arising in this patient
population may prompt them to present to the nearest emergency department (ED),
irrespective of that facility's experience with bariatric surgery. The emergency
physician is the first to evaluate patients with a history of bariatric surgery
who present with abdominal symptoms. As a quality improvement project aimed at
reducing resource utilization, we sought to determine which patients presenting
to the ED could be treated in an outpatient setting in lieu of hospital
admission. Methods: We conducted a retrospective review of bariatric patients
admitted from our ED with abdominal symptoms, including abdominal pain, nausea,
vomiting, dysphagia, obstruction, and hematemesis. We collected the following
variables: type of bariatric operation, admission and discharge diagnoses, and
all interventions performed during admission. Results: One hundred sixty-nine
patients (76.1%) had a history of laparoscopic Roux-en-Y gastric bypass. The time
from bariatric operation to presentation averaged 42 +/- 4.63 (SD) months. The
most common symptom was abdominal pain (80.2%). Ninety-four percent of patients
underwent invasive management via upper endoscopy, laparoscopy, or laparotomy.
The most common postprocedural diagnoses were stricture, bowel obstruction,
inflammatory findings, and cholecystitis. Conclusion: Most patient encounters
resulted in invasive management (204/282; 72.3%). The subset of these patients
requiring endoscopic evaluation or therapy (37.7%) may be suitable for outpatient
management if appropriate measures are available for rapid follow-up and
procedural scheduling.
PMID- 29950799
TI - Image-Guided Navigation in Lymph Node Biopsy.
AB - Background and Objectives: Image-guided navigation is an effective intra
operative technology in select surgical sub-specialties. Laparoscopic and open
lymph node biopsy are frequently undertaken to obtain adequate tissue of
difficult lesions. Image-guided navigation may positively augment the precision
and success of surgical lymph node biopsies. Methods: In this prospective pilot
study, pre-operative imaging was uploaded into the navigation platform software,
which superimposed the imaging and the subject's real-time anatomy. This required
anatomical landmarks on the subject's body to be spatially registered with the
platform using an infrared camera. This was then used to guide dissection and
biopsy in laparoscopic and subcutaneous biopsies. Results: Image-guided lymph
node biopsy was undertaken in 15 cases. Successful biopsy locations included:
retroperitoneum, porta hepatis, mesentery, iliac region, para-aortic, axilla, and
inguinal region. There was an 87% total absolute success rate in biopsies (89% in
laparoscopic image-guided navigation [LIGN] and 83% in subcutaneous image-guided
navigation [SIGN]). There was a 92% absolute success rate in lesions with fixed
locations. There was a 67% absolute success rate in lesions with mobile
locations. Conclusion: The investigators successfully incorporated image-guidance
into surgical biopsy of lymph nodes in a diverse variety of locations. This image
guided technique for surgical biopsy can accurately and safely localize target
lesions minimizing unnecessary dissection, conversion to open procedure, and re
operation for further tissue characterization. This technique was useful in the
morbidly obese, instances of limited foci of disease, PET-active lesions,
identifying areas of highest PET-avidity, and lesions with critical surrounding
anatomy.
PMID- 29950800
TI - The Use of Fluorescence Angiography During Laparoscopic Sleeve Gastrectomy.
AB - Background and Objectives: A new technology involving indocyanine green (ICG)
fluorescence angiography has been introduced to assess tissue perfusion and
perform vascular mapping during laparoscopic surgery. The purpose of this study
was to describe the use of this technology to identify the variable blood supply
patterns to the stomach and gastroesophageal (GE) junction during laparoscopic
sleeve gastrectomy (LSG), which may help in preserving the blood supply and
preventing ischemia-related leaks. Methods: Eighty-six patients underwent LSG and
were examined intraoperatively with fluorescence angiography at an academic
bariatric center from January 2016 to September 2017. Before the construction of
the SG, 1 mL ICG was injected intravenously, and near infrared fluorescence
imaging technology was used to identify the blood supply of the stomach.
Afterward, the LSG was created with attention to preserving the identified blood
supply to the GE junction and gastric tube. Finally, 3 mL ICG was injected to
ensure that all the pertinent blood vessels were preserved. Results: Eighty-six
patients successfully underwent the laparoscopic procedure with no complications.
The following patterns of blood supply to the GE junction were found: (1) a right
side-dominant pattern (20%), arising from the left gastric artery; (2) a right
side-accessory pattern (36%), running in the gastrohepatic ligament and
comprising either an accessory hepatic artery or an accessory gastric artery; and
(3) a left-side accessory pattern arising from tributaries from the left inferior
phrenic artery significantly contributing to the right-side blood supply. In
addition, in 10% of the cases both right and left accessory patterns were present
simultaneously. Conclusion: ICG fluorescence angiography allows determination of
the major blood supply to the proximal stomach before any dissection during
sleeve gastrectomy, so that an effort can be made to avoid unnecessary injury to
these vessels during the procedure.
PMID- 29950801
TI - Laser Angiography to Assess the Vaginal Cuff During Robotic Hysterectomy.
AB - Background and Objectives: Vaginal cuff dehiscence may be a vascular-mediated
event, and reports show a higher incidence after robot-assisted total
laparoscopic hysterectomy (RATLH), when compared with other surgical routes. This
study was conducted to determine the feasibility of using laser angiography to
assess vaginal cuff perfusion during RATLH. Methods: This was a pilot feasibility
trial incorporating 20 women who underwent RATLH for benign disease. Colpotomy
was made with ultrasonic or monopolar instruments, whereas barbed or nonbarbed
suture was used for cuff closure. Time of instrument activation during colpotomy
was recorded. Images were captured of vaginal cuff perfusion before and after
cuff closure. Reviewers evaluated these images and determined areas of adequate
cuff perfusion. Results: Indocyanine green (ICG) was visible at the vaginal cuff
in all participants. Optimal dosage was determined to be 7.5 mg of ICG per
intravenous dose. Mean time to appearance for ICG was 18.4 +/- 7.3 s (mean +/-
SD) before closure and 19.0 +/- 8.7 s after closure. No significant difference (P
= .19) was noted in judged perfusion in open cuffs after colpotomy with a
monopolar (48.9 +/- 26.0%; mean +/- SD) or ultrasonic (40.2 +/- 14.1%) device. No
difference was seen after cuff closure (P = .36) when a monopolar (70.9 +/-
21.1%) or ultrasonic (70.5 +/- 20.5%) device was used. The use of barbed (74.1 +/
20.1%) or nonbarbed (66.4 +/- 20.9%) sutures did not significantly affect
estimated closed cuff perfusion (P = .19). Decreased cuff perfusion was observed
with longer instrument activation times in open cuffs (R2 = 0.3175). Conclusion:
Laser angiography during RATLH allows visualization of vascular perfusion of the
vaginal cuff. The technology remains limited by the lack of quantifiable
fluorescence and knowledge of clinically significant levels of fluorescence.
PMID- 29950803
TI - Evaluative Thinking in Practice: The National Asthma Control Program.
AB - Although evaluative thinking lies at the heart of what we do as evaluators and
what we hope to promote in others through our efforts to build evaluation
capacity, researchers have given limited attention to measuring this concept. We
undertook a research study to better understand how instances of evaluative
thinking may present in practice-based settings-specifically within four state
asthma control programs funded by the Centers for Disease Control and
Prevention's National Asthma Control Program. Through content analyses of
documents as well as interviews and a subsequent focus group with four state
asthma control programs' evaluators and program managers we identified and
defined twenty-two indicators of evaluative thinking. Findings provide insights
about what practitioners may wish to look for when they intend to build
evaluative thinking and the types of data sources that may be more or less
helpful in such efforts.
PMID- 29950802
TI - Self-Expanding Biodegradable Stents for Postoperative Upper Gastrointestinal
Issues.
AB - Background and Objectives: Endoscopic stenting is a minimally invasive treatment
modality for patients with various gastrointestinal conditions. We evaluated the
safety and efficacy of uncovered biodegradable stents for postoperative leaks and
strictures in the upper gastrointestinal tract. Methods: This was a retrospective
study of patients treated endoscopically with biodegradable stents from January
2010 through November 2017. Results: Thirteen patients were enrolled, 7 of whom
were men. Their mean age was 46 (range, 21-82) years. The indications for stent
placement were postoperative leakage and stricture in 9 and 4 patients,
respectively. The primary diagnoses were obesity in 7 patients, gastric cancer in
5, and peptic ulcer in 1. The average time to stent placement after surgery was
35 (range, 17-125) and 166 (range, 153-185) days for patients with postoperative
leakage and stricture, respectively. Stent insertion was successful at the first
attempt in all patients. Complete resolution of the leak and stricture was
achieved after stent application in 11 patients, for a clinical success rate of
85%. The mean follow-up duration was 50 (range, 24-76) months. There were no
major complications. Conclusions: Compared to self-expanding metal and plastic
stents, the main advantages of uncovered biodegradable stents are that they do
not have to be removed and have a low migration rate. Our results suggest that
these stents have promise for management of postoperative gastrointestinal
complications. Further randomized trials with larger sample sizes are necessary
to determine the role of biodegradable stents in the treatment algorithm.
PMID- 29950804
TI - Perfluorocarbon liquid-assisted intraocular foreign body removal.
AB - We describe the benefits of perfluoro-N-octane (PFO), a perfluorocarbon liquid,
in the removal of nonmagnetic intraocular foreign bodies (IOFBs) from the macula
and posterior segment. Two consecutive cases of posterior segment IOFB were
reviewed. An 18-year-old male presented to the emergency room after a motor
vehicle accident with a zone 1 open globe injury and large glass IOFB in the left
eye. A 53-year-old male presented to the emergency room with a history of a 3
week delayed presentation of a zone 1 open globe injury from a nail to the right
eye. He was found to have a metallic IOFB. In both cases, PFO was used to slide
the nonmagnetic IOFBs outside of the macula for safer retrieval. PFO was also
able to protect the posterior pole from IOFB drops during early attempts at
removal. PFO can be a useful surgical adjunct to pars plana vitrectomy in the
removal of certain nonmagnetic IOFBs.
PMID- 29950805
TI - Amniotic membrane extract and eye drops: a review of literature and clinical
application.
AB - The amniotic membrane (AM) has a long history of use in the treatment of various
diseases of the ocular surface. It contains pluripotent cells, highly organized
collagen, anti-fibrotic and anti-inflammatory cytokines, immune-modulators,
growth factors, and matrix proteins. It is used to promote corneal healing in
severely damaged eyes. Recently, AM extract and AM extract eye drops have been
successfully used in clinical applications, including dry eye and chemical burns.
We provide an overview on the recent progress in the preparation, mechanisms of
action, and use of AM extract/AM extract eye drops for corneal and external eye
diseases.
PMID- 29950806
TI - Optic disc vessel density in nonglaucomatous and glaucomatous eyes: an enhanced
depth imaging optical coherence tomography angiography study.
AB - Purpose: To evaluate the ability of enhanced-depth imaging (EDI) optical
coherence tomography angiography (OCTA) to detect vascular signals inside the
glaucomatous optic disc. Patients and methods: Ten glaucomatous eyes of 8
subjects and 11 nonglaucomatous eyes of 7 subjects underwent EDI and conventional
OCTA for optic disc analysis. The optic disc vessel density (VD) at maximum scan
depth (2 mm) was compared between the 2 methods and between glaucomatous and
nonglaucomatous eyes. Regression analysis was used to determine the factors
affecting disc VD. Results: The median (25th, 75th percentile) of the visual
field mean deviation was -20.5 (-25.1, -13.5) dB in glaucoma. The disc VD
measured with the EDI method was significantly greater than that measured with
the conventional method in glaucoma and nonglaucoma. The disc VD was also
significantly lower in glaucoma than in nonglaucoma. The disc VD and mean
deviation were significantly and positively correlated in both methods
(conventional: R2=0.27, EDI: R2=0.22). Conclusion: The correlation between disc
VD and glaucoma severity was comparable between conventional and EDI
measurements. Images obtained with EDI-OCTA have the additional benefit of
revealing more vascular signals in deeper layers. The disc VD, as determined by
both conventional and EDI-OCTA methods, may be an indicator of glaucoma severity.
PMID- 29950807
TI - Color vision deficiency among biomedical students: a cross-sectional study.
AB - Purpose: To determine the prevalence of color vision deficiency (CVD) among first
cycle students of the Faculty of Medicine and Biomedical Sciences of the
University of Yaounde I. Patients and methods: A cross-sectional descriptive
study was carried out between October 1, 2015 and May 31, 2016. Distant visual
acuity was measured and color vision test done for all consenting students.
Ishihara's plates were used to test all the participants. Those who failed the
test were tested with the Roth's 28 Hue test for confirmation of CVD and
classification. Results: A total of 303 students were included, among whom 155
were males (50.8%) and 148 were females (49.2%). The mean age was 20.2+/-2 years.
Five students (1.6%) failed the Ishihara's plate testing. Roth's 28 Hue test
confirmed CVD in 4 of those cases, giving a prevalence of 1.3%. There were equal
numbers of protan and deutan CVD. Conclusion: Despite its low prevalence among
first-cycle students of the Faculty of Medicine and Biomedical Sciences, CVD
screening should be performed in order to raise awareness, which will go a long
way to help orientate the choice of future specialty.
PMID- 29950808
TI - A meta-analysis of Nd:YAG capsulotomy rates for two hydrophobic intraocular lens
materials.
AB - Purpose: The purpose of this study is to estimate and compare neodymium-doped
yttrium aluminum garnet (Nd:YAG) capsulotomy rates for AcrySof (r) and Clareon(r)
intraocular lens (IOL) materials using historical data from the medical
literature and Alcon-sponsored clinical studies. Methods: Clinical trials that
involved the implantation of AcrySof or Clareon monofocal IOLs in subjects with
cataract or presbyopia were extracted from the literature and a company
repository of clinical studies. The study duration, number of eyes, and
cumulative percent of Nd:YAGs for posterior capsule opacification were extracted.
Bayesian random effects meta-analyses were conducted to estimate and compare
outcomes for the 2 different IOL materials. Results: A Bayesian random effects,
meta-analysis was performed that combined a literature review of published
AcrySof Nd:YAG posterior capsulotomy rates and Nd:YAG rates observed in Alcon
sponsored clinical studies of AcrySof and Clareon. Sixteen Alcon studies
contained Nd:YAG data suitable for meta-analysis. Three of these Alcon studies
contained results for the Clareon material (2 one-year studies, and 1 three-year
study). The literature review included 50 papers from 1998 to 2015. In
combination, 30,891 eyes were available for analysis and 2040 Nd:YAG procedures
were reported in studies with a follow-up duration ranging in length from 4
months to 10 years. The overall probability of performing a Nd:YAG capsulotomy
within a year of implant for AcrySof was 1.44% (1.11% to 1.83%) and 0.62% (0.21%
to 1.38%) for Clareon. There was small improvement in the probability of Nd:YAG
within a year of implant for Clareon lenses of about 0.82% with a 95% credible
interval of (0.07% to 1.36%) at 1 year. Results were similar for incidence rates
per 100 surgeries in a year: 0.62 (0.21 to 1.40) for Clareon, 1.46 (1.12 to 1.87)
for AcrySof, and the difference was 0.84 (0.07 to 1.39) favoring Clareon. At 3
years, the overall probability of performing a Nd:YAG capsulotomy for AcrySof was
4.19% (3.24% to 5.30%) compared with only 1.82% (0.63% to 4.02%) for Clareon.
Conclusion: A meta-analysis of Clareon multi-piece and single-piece clinical data
predicts that the cumulative Clareon Nd:YAG probability will be <= AcrySof by
2.37% (0.18% to 3.91%) at 3 years. The results indicate that Clareon is likely to
perform as well as, and possibly better than, AcrySof in terms of Nd:YAG
capsulotomy rates.
PMID- 29950809
TI - Lights and shadows of NSAIDs in bone healing: the role of prostaglandins in bone
metabolism.
AB - In this review, we discuss the current data about the anatomy and function of
bone tissue with particular regard to influence of prostaglandins. Bone tissue
dynamics are characterized by a constant remodeling process that involves all
bone tissue cells. The communication between bone component cells and other
organs is necessary for bone remodeling equilibrium and confirms the dynamic
character of bone tissue. Remodeling is also a vital element of healing processes
and in adapting bone tissue to stress responses. Therefore, in our review we
present the role and significance of bone cells and signaling pathways enabling
maintenance of bone homeostasis and remodeling process stability. Cyclooxygenase
(COX) is a crucial enzyme in the production of prostaglandins and thromboxane. We
focus on the role of COX isoenzymes with highlighting their connection with bone
formation, resorption and repair. Prostaglandins are known as arachidonic acid
metabolites acting through specific membrane receptors and play an important role
in the regulation of osteoblast and osteoclast functions. Prostaglandin PGE2 with
its four defined receptors (EP1R, EP2R, EP3R and EP4R) is crucial to maintain
balanced bone turnover. Their stimulatory or inhibitory effects appear to depend
on different structure-activity relations and signaling pathways. We have
described the role of these receptors in bone metabolism and healing. We conclude
that the activity of prostaglandins in bone tissue is defined by maintaining bone
remodeling balance and its reactions to humoral mediators and mechanical stress.
Most data confirm that among prostaglandins, PGE2 takes part in all processes of
trauma response, including homeostasis, inflammation and healing, and plays a key
role in bone physiology.
PMID- 29950810
TI - Linezolid: a review of its properties, function, and use in critical care.
AB - Linezolid can be considered as the first member of the class of oxazolidinone
antibiotics. The compound is a synthetic antibiotic that inhibits bacterial
protein synthesis through binding to rRNA. It also inhibits the creation of the
initiation complex during protein synthesis which can reduce the length of the
developed peptide chains, and decrease the rate of reaction of translation
elongation. Linezolid has been approved for the treatment of infections caused by
vancomycin-resistant Enterococcus faecium, hospital-acquired pneumonia caused by
Staphylococcus aureus, complicated skin and skin structure infections (SSSIs),
uncomplicated SSSIs caused by methicillin-susceptible S. aureus or Streptococcus
pyogenes, and community-acquired pneumonia caused by Streptococcus pneumoniae.
Analysis of high-resolution structures of linezolid has demonstrated that it
binds a deep cleft of the 50S ribosomal subunit that is surrounded by 23S rRNA
nucleotides. Mutation of 23S rRNA was shown to be a linezolid resistance
mechanism. Besides, mutations in specific regions of ribosomal proteins uL3 and
uL4 are increasingly associated with linezolid resistance. However, these
proteins are located further away from the bound drug. The methicillin-resistant
S. aureus and vancomycin-resistant enterococci are considered the most common
Gram-positive bacteria found in intensive care units (ICUs), and linezolid, as an
antimicrobial drug, is commonly utilized to treat infected ICU patients. The drug
has favorable in vitro and in vivo activity against the mentioned organisms and
is considered as a useful antibiotic to treat infections in the ICU.
PMID- 29950811
TI - Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic
cancer.
AB - Purpose: Pancreatic carcinoma is the neoplasia with the major mortality, and main
standard treatments in this cancer increase survival but do not lead to complete
recovery of the patient. The aim of this study was to evaluate the efficacy of
Abraxane(r) (nab-paclitaxel) in Italian patients with metastatic pancreatic
cancer (MPC). Patients and methods: We conducted a retrospective analysis of 80
patients. Overall survival (OS) was the primary end point for evaluating the
efficacy of nab-paclitaxel in combination with gemcitabine treatment, while
carbohydrate antigen 19-9 (CA 19-9) reduction, safety, progression-free survival
(PFS), overall response rate and reduction in pain were secondary end points.
Results: The median OS was 8 months, and the median PFS was 5 months. A
considerable difference in CA 19-9 before and after treatment was observed.
Descriptive and correlation analyses were done to examine the relationship
between CA 19-9 response and OS. Linear regression analysis between OS and CA 19
9 response revealed that CA 19-9 is an important predictor of OS, showing a
positive correlation. Conclusion: Nab-paclitaxel is a well-tolerated and
effective treatment for patients affected by MPC. The drug showed an improved
tolerability profile, significant pain relief and an increase in survival rate.
PMID- 29950812
TI - Use of levosimendan in the treatment of cerebral vascular vasospasm: a case
study.
AB - Despite the progress in the management of cerebral arterial aneurysms,
subarachnoid hemorrhage (SAH) remains the major cause of neurological disability.
While SAH-related deaths usually occur as a result of brain impairment due to
hemorrhage, permanent neurological deficits are caused by cerebral ischemia due
to edema and spasm of cerebral arteries. Additionally, ~20%-30% of patients with
SAH develop secondary cardiomyopathy; this phenomenon is known as neurogenic
stress cardiomyopathy (NSC), which is associated with increased mortality and
poor long-term prognosis. Levosimendan is a new inotropic drug that causes
calcium sensitization of troponin C, thus increasing contraction force of
myofilaments. The drug also causes opening of ATP-dependent potassium channels in
vascular smooth muscles, which results in dilatation of veins and arteries,
including cerebral arteries. To date, there have been several reports of
levosimendan application in patients with SAH and neurogenic stress
cardiomyopathy, and the effect of the drug on vasospasm has been previously
advocated. This paper presents a case report of a 57-year-old patient with
massive SAH, where levosimendan was used for reducing vasospasm.
PMID- 29950813
TI - Design, synthesis, docking, and antimicrobial evaluation of some novel
pyrazolo[1,5-a] pyrimidines and their corresponding cycloalkane ring-fused
derivatives as purine analogs.
AB - Background: Over the years, pyrazolopyrimidine derivatives have been recognized
as having antimicrobial activities. Recently, we reported different synthetic
methods to prepare pyrazolopyrimidine derivatives as anticancer and antimicrobial
agents. The studies showed that our previously reported 5-aminopyrazoles 2 act as
a building block for the preparation of a variety of interesting
pyrazolopyrimidines as purine analogs. Purpose: The objective of this study was
to describe the direct new method for preparation of novel pyrazolo[1,5
a]pyrimidine derivatives and their corresponding cycloalkane ring-fused
derivatives. Also, the new compounds were tested in vitro for their antibacterial
and antifungal activity properties. Methods: Pyrazolo[1,5-a]pyrimidine
derivatives were prepared by the reaction of our previously reported 5
aminopyrazoles 2 with suitable sodium salts of (hydroxymethylene) cycloalkanones
and sodium salts of unsaturated ketones. Results: The structures of the new
compounds were characterized according to their mass spectroscopy, 1H NMR, IR and
elemental analyses. Compounds 8b, 10e, 10i, and 10n were the most active
compounds against Gram-positive and Gram-negative bacterial species. Compound 10i
with two moieties of 4-Br-C6H4 revealed increased reactivity compared with
ampicillin as standard reference. Conclusion: About twenty two novel pyrazolo[1,5
a]pyrimidine derivatives and their corresponding cycloalkane ring-fused
derivatives were prepared through the reaction of 5-aminopyrazoles 2 with
different sodium salts of (hydroxymethylene) cycloalkanones and sodium salts of
unsaturated ketones. The antibacterial and antifungal activities of the newly
synthesized compounds were evaluated and revealed that compounds 8b, 10e, 10i,
and 10n were the most active compounds against Gram-positive and Gram-negative
bacterial strains.
PMID- 29950814
TI - Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective
uric acid reabsorption inhibitor, in healthy Japanese and non-Asian male
subjects.
AB - Purpose: Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in
clinical development for treatment of gout and asymptomatic hyperuricemia. This
study evaluated verinurad pharmacokinetics, pharmacodynamics, and tolerability in
healthy Japanese and non-Asian adult male subjects. Methods: This was a Phase I,
randomized, single-blind, placebo-controlled study. Panels of 8 Japanese subjects
were randomized to receive oral verinurad (2.5-15 mg) or placebo administered as
a single dose in a fasted and fed state and as once-daily doses for 7 days in a
fed state. Eight non-Asian subjects received verinurad 10 mg as a single dose
(fasted and fed) and multiple doses in the fed state. Serial plasma/serum and
urine samples were assayed for verinurad and uric acid. Safety was assessed by
adverse events and laboratory data. Results: Of 48 randomized subjects, 46
(Japanese, 39; non-Asian, 7) completed the study. Following single or multiple
doses in Japanese subjects, maximum plasma concentration (Cmax) and area under
the plasma concentration-time curve (AUC) increased in a near dose-proportional
manner. Time to Cmax (Tmax) was ~1.25-2.0 hours with fasting. A moderate-fat meal
delayed Tmax (range 3.0-5.0 hours) and had a variable effect on AUC (0%-97%
increase) and Cmax (0%-26% increase) across the dose groups. Following multiple
verinurad 10 mg doses, Cmax and AUC were 38% and 23% higher, respectively, in
Japanese vs non-Asian subjects, largely due to body weight differences. Mean
reduction of serum urate following multiple verinurad 10 mg doses was 46% and 44%
after 24 hours in Japanese and non-Asian subjects, respectively. Verinurad was
well tolerated at all doses. Conclusion: Verinurad monotherapy lowered serum
urate and was well tolerated in both healthy Japanese and non-Asian males, while
small differences in plasma pharmacokinetics were observed. These data support
further evaluation of once-daily verinurad as a treatment for gout and
asymptomatic hyperuricemia.
PMID- 29950815
TI - Positives and negatives of nonsteroidal anti-inflammatory drugs in bone healing:
the effects of these drugs on bone repair.
AB - Tissue damage following injury triggers the processes of coagulation,
inflammation and healing. In tissues surrounding the bone, the result of the
healing process is a scar, while bone tissue has a unique ability to achieve
shape, strength and pre-injury function. Bone healing is a process of
regeneration rather than classic recovery. The result of this process is the
formation of new, healthy bone tissue instead of a scar. Many factors can inhibit
or impair the bone healing process, and their influence is critical during the
stages of inflammation and angiogenesis and finally on the clinical outcome.
Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential role associated
with their analgesic potency and anti-inflammatory effects. NSAIDs are also the
most often used drugs in patients who require pain control and inflammation
reduction due to musculoskeletal diseases or injures. Although their analgesic
effect is well documented, NSAIDs also interfere with bone healing; therefore,
the relative benefits and disadvantages connected with their administration
should be taken into consideration. Despite the negative effect, NSAIDs have
beneficial properties, but their clinical benefits in relation to dose and time
of use are still unclear. Therefore, in this review, we focus on bone healing
with relation to the impact of NSAIDs.
PMID- 29950816
TI - Novel methods to estimate antiretroviral adherence: protocol for a longitudinal
study.
AB - Background: There is currently no gold standard for assessing antiretroviral
(ARV) adherence, so researchers often resort to the most feasible and cost
effective methods possible (eg, self-report), which may be biased or inaccurate.
The goal of our study was to evaluate the feasibility and acceptability of
innovative and remote methods to estimate ARV adherence, which can potentially be
conducted with less time and financial resources in a wide range of clinic and
research settings. Here, we describe the research protocol for studying these
novel methods and some lessons learned. Methods: The 6-month pilot study aimed to
examine the feasibility and acceptability of a remotely conducted study to
evaluate the correlation between: 1) text-messaged photographs of pharmacy refill
dates for refill-based adherence; 2) text-messaged photographs of pills for pill
count-based adherence; and 3) home-collected hair sample measures of ARV
concentration for pharmacologic-based adherence. Participants were sent monthly
automated text messages to collect refill dates and pill counts that were taken
and sent via mobile telephone photographs, and hair collection kits every 2
months by mail. At the study end, feasibility was calculated by specific metrics,
such as the receipt of hair samples and responses to text messages. Participants
completed a quantitative survey and qualitative exit interviews to examine the
acceptability of these adherence evaluation methods. The relationship between the
3 novel metrics of adherence and self-reported adherence will be assessed.
Discussion: Investigators conducting adherence research are often limited to
using either self-reported adherence, which is subjective, biased, and often
overestimated, or other more complex methods. Here, we describe the protocol for
evaluating the feasibility and acceptability of 3 novel and remote methods of
estimating adherence, with the aim of evaluating the relationships between them.
Additionally, we note the lessons learned from the protocol implementation to
date. We expect that these novel measures will be feasible and acceptable. The
implications of this research will be the identification and evaluation of
innovative and accurate metrics of ARV adherence for future implementation.
PMID- 29950817
TI - Computerized adaptive testing with decision regression trees: an alternative to
item response theory for quality of life measurement in multiple sclerosis.
AB - Background: The aim of this study was to propose an alternative approach to item
response theory (IRT) in the development of computerized adaptive testing (CAT)
in quality of life (QoL) for patients with multiple sclerosis (MS). This approach
relied on decision regression trees (DRTs). A comparison with IRT was undertaken
based on precision and validity properties. Materials and methods: DRT- and IRT
based CATs were applied on items from a unidi-mensional item bank measuring QoL
related to mental health in MS. The DRT-based approach consisted of CAT
simulations based on a minsplit parameter that defines the minimal size of nodes
in a tree. The IRT-based approach consisted of CAT simulations based on a
specified level of measurement precision. The best CAT simulation showed the
lowest number of items and the best levels of precision. Validity of the CAT was
examined using sociodemographic, clinical and QoL data. Results: CAT simulations
were performed using the responses of 1,992 MS patients. The DRT-based CAT
algorithm with minsplit = 10 was the most satisfactory model, superior to the
best IRT-based CAT algorithm. This CAT administered an average of nine items and
showed satisfactory precision indicators (R = 0.98, root mean square error [RMSE]
= 0.18). The DRT-based CAT showed convergent validity as its score correlated
significantly with other QoL scores and showed satisfactory discriminant
validity. Conclusion: We presented a new adaptive testing algorithm based on DRT,
which has equivalent level of performance to IRT-based approach. The use of DRT
is a natural and intuitive way to develop CAT, and this approach may be an
alternative to IRT.
PMID- 29950818
TI - Medication practices and experiences of older adults discharged home from
hospital: a feasibility study protocol.
AB - Background: Switzerland's aging population raises pressing questions about
maintaining older adults in their home environments and the problems associated
with managing complex treatments requiring medication in such contexts. Few
studies have examined older adults' experiences of changes in their medication on
discharge home following hospitalization for illness or an accident. Similarly,
few studies have evaluated the involvement of informal and professional
caregivers in the medication practices used with older adults living at home.
However, medication practices are complex and understanding them requires an
interest in their underlying logic and the interactions that constitute them.
This study will explore the feasibility of recruiting older adults and then
collecting and analyzing data on their medication practices and their experiences
of discharge home after hospitalization for an illness or following an accident.
Furthermore, it will describe the involvement of informal caregivers and homecare
professionals in these processes. Design and methods: The study will use a
qualitative methodology. The first phase will be developed in the general
medicine and surgery wards of Sion hospital and in the town's community
healthcare center. This phase will aim to build a close collaboration between the
research team and the health care professionals of Valais hospitals and the
community healthcare center. It will enable data collection from professional
caregivers to identify the tools, and potentially the interventions, which are
used to prepare older adults for hospital discharge and return home, particularly
with regard to the medication prescribed to them. In the second phase, semi
structured interviews will be conducted with eight patients aged 75 years old or
more who have returned home after hospitalization. Interviews will also be
conducted with their informal and professional caregivers. Conclusion: This
feasibility study will enable the identification of tools that leverage improved
adhesion to a medical treatment that has been adjusted and stabilized following
discharge home from hospital. It will incorporate the points of view of older
adults and the different stakeholders involved in the management of their
medication and the development of tangible solutions to encourage treatment
adhesion on discharge home. This study's findings will enable us to design a much
larger future study.
PMID- 29950819
TI - Development and assessment of reliable patient-based hypodontia website.
AB - Background: The aim of the study was to develop a high-quality valid patient
information website with regard to hypodontia and its management, and to test its
effectiveness in delivering this information. Methods: A patient-based hypodontia
website was created and placed on the Trust's website. It was then validated
using five website assessment tools: Flesch reading ease score, LIDA, DISCERN,
Journal of American Medical Association and Health on the Net seal. A cross
sectional prospective design was adopted using a 15-item questionnaire to assess
the effectiveness of the newly created hypodontia website in helping participants
understand their management. New patients attending their first hypodontia clinic
consultation appointment were invited to complete the questionnaire both before
and after visiting the website. Results: The newly created hypodontia website
scored well with the website validation tools in comparison with previously
assessed hypodontia websites. Forty participants (25 female) took part in the
questionnaire study, with a mean age of 15.3 (SD 6.1) years. After visiting the
website, 85% of participants felt the website was helpful in understanding
hypodontia, with an observed improvement in all domains of the questionnaire,
reaching statistical significance (p<0.05-0.001) in 10 of the 15 items.
Conclusion: This study found that patients felt that a hypodontia website was
effective in improving their perceived knowledge of hypodontia.
PMID- 29950820
TI - Humanistic outcomes and patient acceptance of the pharmacist-led medication
review "Polymedication Check" in primary care in Switzerland: a prospective
randomized controlled trial.
AB - Background: Since 2010, Swiss pharmacists have been offering their patients a
Polymedication Check (PMC), a new cognitive pharmacy service in the form of a
medication review for patients taking >=4 prescribed medicines for a period >3
months. While a first publication of this project reported on the impact of the
PMC on patients' adherence, the present paper focuses on humanistic outcomes.
Methods: This randomized controlled trial was conducted in 54 Swiss community
pharmacies. After recruitment, the intervention group underwent a PMC in the
pharmacy (T-0) and 28 weeks after T-0 (T-28), while the control group did not
receive the PMC until 28 weeks after the study started (T-28). A clinical
psychologist, blinded to the intervention, interviewed the patients 2 weeks (T-2)
and 16 weeks (T-16) after T-0. Interviewer and patient both rated patient's
knowledge of own medicines use. Furthermore, patients reported satisfaction with
their pharmacy and appraisal of their medicines use. The availability of a
written medication plan was assessed at T-16. Acceptance of the service was
measured using a patient's self-report questionnaire at T-28. Results: General
linear model analysis for knowledge about medicines revealed a significant effect
on the factor "group" (P=5.86, p=0.016), indicating that the intervention group
had higher ratings for knowledge about their medication at T-2 and T-16 compared
to controls. The majority (83%) of patients judged the counseling by the
pharmacist as being helpful for their daily medication management. Availability
of a written medication plan was comparable in both groups (52.5% vs 52.7%,
p>0.05). Conclusion: For the first time, the benefits of a complex pharmacist-led
intervention were evaluated in Swiss primary care with a randomized controlled
trial. The PMC increased patients' subjective knowledge of their medicines
compared to no medication review. The effect remained sustainable over time.
Recommendations resulting from the pharmacist-led service were highly appreciated
by the patients.
PMID- 29950821
TI - Elicitation of health state utilities associated with the mode of administration
of drugs acting on the prostacyclin pathway in pulmonary arterial hypertension.
AB - Introduction: Pulmonary arterial hypertension (PAH) is a rare, incurable disease
associated with decreased life expectancy and a marked impact on quality of life
(QoL). There are three classes of drugs available for treatment: endothelin
receptor antagonists (ERA), drugs acting on nitric oxide pathway (riociguat and
phosphodiesterase type 5 inhibitors [PDE5i]), and drugs acting on prostacyclin
pathway. The latter have widely different modes of administration - continuous
intravenous infusion, continuous subcutaneous infusion, inhaled, and oral - each
associated with variable treatment burden, and implications for health economic
assessment. This study aimed to establish utility values associated with
different modes of administration of drugs acting on the prostacyclin pathway for
use in economic evaluations of PAH treatments. Methods: A UK general public
sample completed the EQ-5D-5L and valued four health states in time trade-off
interviews. The health states drafted from literature and interviews with PAH
experts (n=3) contained identical descriptions of PAH and ERA/PDE5i treatment,
but differed in description of administration including oral (tablets), inhaled
(nebulizer), continuous subcutaneous infusion, and continuous intravenous
infusion. Results: A total of 150 participants (63% female; mean age 37 years)
completed interviews. Utilities are presented as values between 0 and 1, with 0
representing the state of being dead and 1 representing being in full health. The
mean (SD) utility for oral health state was 0.85 (0.16), while all other health
states were significantly lower at 0.74 (0.27) for inhaled (p=0.001), 0.59 (0.31)
for subcutaneous (p<0.001) and 0.54 (0.32) for intravenous (p<0.001), indicating
that there are disutilities (negative differences) associated with non-oral
health states. Disutilities were -0.11 for inhaled, -0.26 for subcutaneous, and
0.31 for intravenous administration. Conclusion: The results demonstrate
quantifiable QoL differences between modes of administration of drugs acting on
the prostacyclin pathway. QoL burden should be considered for economic evaluation
of drugs for PAH treatment.
PMID- 29950822
TI - Clinical empathy with cancer patients: a content analysis of oncology nurses'
perception.
AB - Background: Empathy is one of the most important communication skills in clinical
practice, specifically in the field of oncology. Empathic competences have a
significant meaning for caring and therapeutic relations in nurses'
responsibilities. Clinical empathy brings positive performance, thus patients'
emotions are perceived and expressed more easily. Clinical empathy is contextual,
interpersonal and affective, but it is also difficult to study. Awareness of
oncology nurses' perception of this phenomenon might help them to plan for more
effective patient-centered consultations within interventional programs.
Therefore, the aim of this study was to explore the content of clinical empathy
with cancer patients from the perspective of oncology nurses. Patients and
methods: In this qualitative study, 15 oncology nurses were selected by purposive
sampling. A semi-structured face-to-face interview was conducted with each of the
participants. After data collection, all interviews were transcribed and
reviewed, and then primary codes, sub-categories and categories were extracted.
The data were analyzed with the conventional content analysis method by MAXQDA 10
software. Results: Clinical empathy showed a composite construct with five main
categories, including co-presence (physical and emotional presence),
metacognition (self-awareness of mental processes), perception (knowing about
awareness of individuals), inherent (genetic) and didactic (instructive) nature.
Conclusion: Clinical empathy as an effective strategy can be taught through three
areas of "co-presence", "metacognition" and "perception" in the context of cancer
care. Thus, clinical empathy should be considered as one of the competency
standards which can be taught to oncology nurses.
PMID- 29950823
TI - IL-6, PF-4, sCD40 L, and homocysteine are associated with the radiological
progression of cerebral small-vessel disease: a 2-year follow-up study.
AB - Background: Endothelial dysfunction (ED) is involved in the pathogenesis of
cerebral small vessel disease (SVD), however, it is not clear if specific
biomarkers related to ED are associated with radiological progression of SVD.
Methods: A single-center, prospective cohort study was conducted among
consecutive, adult patients with SVD. Logistic regression was used to analyze the
association of each baseline biomarker (highest vs lowest tertile) and the MRI
radiological outcome after 2 years. The mean Z-score for vascular inflammation
(VI) combined soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble
platelet selectin (sP-selectin), CD40 ligand (sCD40 L), platelet factor-4 (PF-4)
and homocysteine; Z-score for systemic inflammation (SI) combined high
sensitivity C-reactive protein (hsCRP), interleukin-1alpha and -6 (IL-1alpha and
IL-6, respectively) and tumor necrosis factor-alpha (TNF-alpha). Results: The
study group comprised 123 patients (age, mean+/-SD: 72.2+/-8 years, 49% females),
with lacunar stroke (n=49), vascular dementia (n=48), and vascular parkinsonism
(n=26). Moreover, 34.9% patients experienced radiological progression, 43% had
progression of isolated white matter lesions (WMLs), 23.2% had new lacunes, and
34.8% had both WMLs progression and new lacunes. After adjustment for confounders
(age, sex, blood pressure, MRI lesions load), the PF-4 (OR; 95% CI 5.5; 1.5-21),
sCD40L (4.6; 1.1-18.6), IL-6 (7.4; 1.48-37), Z-score for VI (4.5; 1.1-18.6), and,
marginally, homocysteine (4.1; 0.99-17) were associated with the risk of any
radiological progression; further, homocysteine (2.4; 1.4-14), Z-score for SI
(2.1; 1.2-14) and, marginally, IL-6 (6.0; 0.95 -38) were related to the
development of new lacunes; PF-4 (7.9; 1.6-38) and, marginally, the Z-score for
VI (4.2; 0.9-19.5) were correlated with the risk of WMLs progression. Additional
adjustment for clinical SVD manifestations did not significantly alter the
results. Conclusion: The data supports the concept that ED modulates the
radiological progression of SVD and WMLs and lacunes are associated with
different inflammatory markers.
PMID- 29950824
TI - Thoracopelvic assisted movement training to improve gait and balance in elderly
at risk of falling: a case series.
AB - Background: Age-related changes in coordinated movement pattern of the thorax and
pelvis may be one of the factors contributing to fall risk. This report describes
the feasibility of using a new thoracopelvic assisted movement device to improve
gait and balance in an elderly population with increased risk for falls. Methods:
In this case series, 19 older adults were recruited from an assisted living
facility. All had gait difficulties (gait speed <1.0 m/s) and history of falls.
Participants received 12 training sessions with the thoracopelvic assisted
movement device. Functional performance was measured before, during (after 6
sessions), and after the 12 sessions. Outcomes measures were Timed Up and Go,
Functional Reach Test, and the 10-meter Walk Test. Changes in outcomes were
calculated for each participant in the context of minimal detectable change (MDC)
values. Results: More than 25% of participants showed changes >MDC in their
clinical measures after 6 treatment sessions, and more than half improved >MDC
after 12 sessions. Six subjects (32%) improved their Timed Up and Go time by >4
seconds after 6 sessions, and 10 (53%) after 12 sessions. After the intervention,
4 subjects (21%) improved their 10-meter Walk Test velocity from limited
community ambulation (0.4-0.8 m/s) to functional community ambulation (>0.8 m/s).
Conclusion: Thoracopelvic assisted movement training that mimics normal walking
pattern may have clinical implications, by improving skills that enhance balance
and gait function. Additional randomized, controlled studies are required to
examine the effects of this intervention on larger cohorts with a variety of
subjects.
PMID- 29950825
TI - AKI in the very elderly patients without preexisting chronic kidney disease: a
comparison of 48-hour window and 7-day window for diagnosing AKI using the KDIGO
criteria.
AB - Objectives: To compare the differences between the Kidney Disease Improving
Global Outcomes (KDIGO) criteria of the 48-hour window and the 7-day window in
the diagnosis of acute kidney injury (AKI) in very elderly patients, as well as
the relationship between the 48-hour and 7-day windows for diagnosis and 90-day
mortality. Patients and methods: We retrospectively enrolled very elderly
patients (>=75 years old) from the geriatrics department of the Chinese PLA
General Hospital between January 2007 and December 2015. AKI patients were
divided into 48-hour and 7-day groups by their diagnosis criteria. AKI patients
were divided into survivor and nonsurvivor groups by their outcomes within 90
days after diagnosis of AKI. Results: In total, 652 patients were included in the
final analysis. The median age of the cohort was 87 (84-91) years, the majority
(623, 95.6%) of whom were male. Of the 652 AKI patients, 334 cases (51.2%) were
diagnosed with AKI by the 48-hour window for diagnosis, while 318 cases (48.8%)
were by the 7-day window for diagnosis. The 90-day mortality was 42.5% in
patients with 48-hour window AKI and 24.2% in patients with 7-day window AKI.
Kaplan-Meier curves showed that 90-day mortality was lower in the 7-day window
AKI group than in the 48-hour window AKI group (log rank: P<0.001). Multivariate
analysis by the Cox model revealed that 48-hour window for diagnosis hazard ratio
(HR=1.818; 95% CI: 1.256-2.631; P=0.002) was associated with higher 90-day
mortality. Conclusion: The 90-day mortality was higher in 48-hour window AKI than
in 7-day window AKI in very elderly patients. The 48-hour KDIGO window definition
may be less sensitive. The 48-hour KDIGO window definition is significantly
better correlated with subsequent mortality and is, therefore, still appropriate
for clinical use. Finding early, sensitive biomarkers of kidney damage is a
future direction of research.
PMID- 29950826
TI - Efficacy and safety of four doses of glycopyrrolate/formoterol fumarate delivered
via a metered dose inhaler compared with the monocomponents in patients with
moderate-to-severe COPD.
AB - Purpose: To determine the efficacy and safety of glycopyrrolate/formoterol
fumarate metered dose inhaler (GFF MDI 36/9.6, 36/7.2, 18/9.6, 9/9.6 ug) using
innovative co-suspension delivery technology, compared with glycopyrrolate (GP)
MDI 36 ug and formoterol fumarate (FF) MDI 9.6 ug, in patients with moderate-to
severe COPD. Methods: In this Phase IIb, randomized, double-blind, balanced
incomplete-block, two-period, cross-over study (NCT01349816), patients received
treatment twice-daily for 7 days. The primary efficacy endpoint was forced
expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours
(AUC0-12) on Day 7. Secondary efficacy endpoints were peak change from baseline
in FEV1 through 2 hours; time to onset of action (>=10% improvement in mean
FEV1); proportion of patients achieving >=12% improvement in FEV1 on Day 1; peak
change from baseline in inspiratory capacity (IC) on Days 1 and 7; change from
baseline in morning pre-dose FEV1; peak change from baseline in FEV1 through 6
hours; and change from baseline in mean evening 12-hour post-dose trough FEV1 on
Day 7. Safety was assessed. Results: All 185 randomized patients received
treatment. All doses of GFF MDI significantly improved the primary endpoint
compared with GP MDI 36 ug (all P<=0.0137). For peak change in FEV1 and IC and
time to onset of action secondary endpoints, >=2 doses of GFF MDI demonstrated
superiority to GP MDI 36 ug. No significant differences were observed between GFF
MDI and FF MDI 9.6 ug for primary and secondary endpoints. The incidence of
adverse events was similar between treatments. Conclusion: While all doses of GFF
MDI were superior to GP MDI 36 ug for the primary end-point, in this study
neither superiority of GFF MDI to FF MDI 9.6 ug nor a clear dose-response was
observed. All treatments were well tolerated with no unexpected safety findings.
PMID- 29950827
TI - Clinical characteristics of patients newly diagnosed with COPD by the fixed ratio
and lower limit of normal criteria: a cross-sectional analysis of the TargetCOPD
trial.
AB - Background: Consensus on the definition of airflow obstruction to diagnose COPD
remains unresolved. Methods: We undertook systematic case finding for COPD in
primary care using the fixed ratio (FR) criterion (forced expiratory volume in 1
s/forced vital capacity [FEV1/FVC] <0.7) for defining airflow obstruction and
also using the lower limit of normal (LLN). We then compared the clinical
characteristics of those identified by the 2 criteria. Results: A total of 3,721
individuals reporting respiratory symptoms were invited for spirometry. A total
of 2,607 attended (mean age 60.4 years, 52.8% male, 29.8% current smokers) and
32.6% had airflow obstruction by FR ("FR+") and 20.2% by LLN ("LLN+"). Compared
with the LLN+/FR+ group, the LLN-/FR+ group (12.4%) was significantly older, had
higher FEV1 and FEV1/FVC, lower COPD assessment test scores, and less cough,
sputum, and wheeze, but was significantly more likely to report a diagnosis of
heart disease (14.2% versus 6.9%, p<0.001). Compared with the LLN+/FR+ group, the
LLN-/FR- group was younger, had a higher body mass index, fewer pack-years, a
lower prevalence of respiratory symptoms except for dyspnea, and lower FVC and
higher FEV1. The probability of known heart disease was significantly lower in
the LLN+/FR+ group compared with those with preserved lung function (LLN-/FR-)
(adjusted odds ratio 0.62, 95% CI: 0.43-0.90) but this was not seen in the LLN
/FR+ group (adjusted odds ratio 0.90, 95% CI: 0.63-1.29). Conclusion: In
symptomatic individuals, defining airflow obstruction by FR instead of LLN
identifies a significant number of individuals who have less respiratory and more
cardiac clinical characteristics.
PMID- 29950828
TI - Zinc oxide nanoparticles induce toxicity in CAL 27 oral cancer cell lines by
activating PINK1/Parkin-mediated mitophagy.
AB - Background: Tongue squamous cell carcinoma (tongue cancer) is one of the most
common malignancies in the oral maxillofacial region. The tumor easily relapses
after surgery, and the prognosis remains poor. Recently, zinc oxide nanoparticles
(ZnO NPs) were shown to target multiple cancer cell types. In this study, we
aimed to elucidate the anticancer effect of ZnO NPs on CAL 27 human tongue cancer
cells and identify the role of PINK1/Parkin-mediated mitophagy in this effect.
Materials and methods: We analyzed the dose-dependent cytotoxic effects of ZnO
NPs on CAL 27 cells. Cells were cultured in media containing 0, 5, 10, 20, 30,
40, 50, 60, 70, 80, 90, or 100 MUg/mL ZnO NPs for 24 h. We further examined the
intracellular reactive oxygen species levels, monodansylcadaverine intensity and
mitochondrial membrane potential following the administration of 25 MUg/mL ZnO
NPs for 4, 8, 12, or 24 h and investigated the role of PINK1/Parkin-mediated
mitophagy in ZnO NP-induced toxicity in CAL 27 cells. Results: The viability of
CAL 27 cells decreased after treatment with increasing ZnO NP concentrations. The
inhibitory concentration 50% of the ZnO NPs was calculated as 25 MUg/mL. The ZnO
NPs increased the intracellular reactive oxygen species levels and decreased the
mitochondrial membrane potential in a time-dependent manner as well as activated
the PINK1/Parkin-mediated mitophagy process in CAL 27 cells. Conclusion: Based on
our findings, ZnO NPs may possess potential anticancer activity toward tongue
cancer cells.
PMID- 29950829
TI - Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of
concept studies in breast cancer.
AB - Background: Trastuzumab plus docetaxel is a mainstay to treat HER2-positive
breast cancers. However, developing nanoparticles could help to improve the
efficacy/toxicity balance of this doublet by improving drug trafficking and
delivery to tumors. This project aimed to develop an immunoliposome in breast
cancer, combining docetaxel encapsulated in a stealth liposome engrafted with
trastuzumab, and comparing its performances on human breast cancer cell lines
with standard combination of docetaxel plus trastuzumab. Methods: Several
strategies to engraft trastuzumab to pegylated liposomes were tested.
Immunoliposomes made of natural (antibody nanoconjugate-1 [ANC-1]) and synthetic
lipids (ANC-2) were synthesized using standard thin film method and compared in
size, morphology, docetaxel encapsulation, trastuzumab engraftment rates and
stability. Antiproliferative activity was tested on human breast cancer models
ranging from almost negative (MDA-MB-231), positive (MDA-MB-453) to
overexpressing (SKBR3) HER2. Finally, cell uptake of ANC-1 was studied by
electronic microscopy. Results: ANC-1 showed a greater docetaxel encapsulation
rate (73%+/-6% vs 53%+/-4%) and longer stability (up to 1 week) as compared with
ANC-2. Both ANC presented particle size <=150 nm and showed similar or higher in
vitro antiproliferative activities than standard treatment, ANC-1 performing
better than ANC-2. The IC50s for docetaxel combined to free trastuzumab were
8.7+/-4, 2+/-0.7 and 6+/-2 nM with MDA-MB-231, MDA-MB-453 and SKBR3,
respectively. The IC50s for ANC-1 were 2.5+/-1, 1.8+/-0.6 and 3.4+/-0.8 nM and
for ANC-2 were 1.8+/-0.3 nM, 2.8+/-0.8 nM and 6.8+/-1.8 nM with MDA-MB-231, MDA
MB-453 and SKBR3, respectively. Cellular uptake appeared to depend on HER2
expression, the higher the expression, the higher the uptake. Conclusion: In
vitro results suggest that higher antiproliferative efficacy and efficient drug
delivery can be achieved in breast cancer models using nanoparticles.
PMID- 29950830
TI - Dual-layer aligned-random nanofibrous scaffolds for improving gradient
microstructure of tendon-to-bone healing in a rabbit extra-articular model.
AB - Background: Tendon/ligament injuries are common sports injuries. Clinically, the
repair of a ruptured tendon or ligament to its bony insertion is needed, but the
enthesis structure is not well reestablished following surgical repair. Herein,
we fabricated dual-layer aligned-random scaffold (ARS) by electrospinning and
aimed to investigate the effect of the scaffold on tendon-to-bone healing in
vivo. Materials and methods: The random and dual-layer aligned-random silk fbroin
poly(L-lactic acid-co-e-caprolactone) (P(LLA-CL)) nanofibrous scaffolds were
successfully fabricated by electrospinning methods. Ninety New Zealand white
rabbits were randomly divided into three groups (random scaffold [RS], ARS, and
control groups), and they were subjected to surgery to establish an extra
articular tendon-to-bone healing model with autologous Achilles tendon. Results:
Histological assessment showed that the ARS significantly increased the area of
metachromasia, decreased the interface width, and improved collagen maturation
and organization at the tendon-bone interface compared with the RS and control
groups. Microcomputed tomography analysis showed that the bone tunnel area of RS
and ARS groups was significantly smaller than those of the control group. Real
time polymerase chain reaction showed that BMP-2 and osteopontin expression
levels of the tissue at the interface between the bone and graft in the RS and
ARS groups were higher than those of the control group at 6 weeks. Collagen I
expression level of the ARS group was significantly higher than those of the RS
and control groups at 6 and 12 weeks. Moreover, the ARS groups had a better
ultimate load-to-failure and stiffness than the RS and control groups.
Conclusion: ARS could effectively augment the tendon-to-bone integration and
improve gradient microstructure in a rabbit extra-articular model by inducing the
new bone formation, increasing the area of fibrocartilage, and improving collagen
organization and maturation. The dual-layer aligned-random silk fibroin/P(LLA-CL)
nanofibrous scaffold is proved to be a promising biomaterial for tendon-to-bone
healing.
PMID- 29950831
TI - Construction of injectable, pH sensitive, antibacterial, mineralized amino acid
yolk-shell microspheres for potential minimally invasive treatment of bone
infection.
AB - Introduction: Treatment of infection within bone is difficult, and conventional
surgical treatment brings intense pain to the patients physically and mentally.
There is an urgent need to develop injectable nano- and/or micro-medicine for
minimally invasive treatment of osteomyelitis. Methods: In this paper, amino acid
(L-lysine [Lys]) was mineralized into yolk-shell structured CaCO3 microspheres
(MSs). The morphologies of the obtained MSs were investigated by scanning
electron microscopy and transmission electron microscopy. The composition of
CaCO3 MSs was identified by using Fourier transform infrared spectroscopy. The as
prepared CaCO3 MSs were examined with power X-ray diffraction analysis to obtain
the crystallographic structure of the MSs. Results: The as prepared Lys
encapsulated CaCO3 MSs (Lys@CaCO3 MSs) were used as micro-drug to improve acidic
environment of osteomyelitis caused by bacterial infection and promote osteoblast
proliferation under oxidative stress. These pH responsive Lys@CaCO3 MSs have a
drug loading efficiency of 89.8 wt % and drug loading content (DLC) of 22.3 wt %.
Conclusion: Our results demonstrated that Lys@CaCO3 MSs can effectively kill
Staphylococcus aureus and promote proliferation and differentiation of
osteoblasts under stimulation of H2O2 at pH = 5.5.
PMID- 29950832
TI - Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co
polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy
therapy.
AB - Introduction: Diabetic nephropathy (DN) is the primary root of morbidity and
mortality in diabetic patients. Unfortunately, currently, no effective
therapeutic strategies are available to ameliorate and reverse the progression of
DN. Rhein (RH) is an anthraquinone derivative extracted from herbal medicines
with various pharmacological effects on DN. However, its clinical administration
is limited by its poor solubility, low bioavailability, reduced distribution into
the kidney and adverse effects. Methods and results: To improve the delivery of
RH into kidney and the therapeutic effect on DN, we synthesized and utilized
polyethyleneglycol-co-polycaprolactone-co-polyethylenimine triblock amphiphilic
polymers to prepare RH-loaded polyethyleneglycol-co-polycaprolactone-co
polyethylenimine nanoparticles (PPP-RH-NPs). PPP-RH-NP size was optimized to 75
+/- 25 nm for kidney-targeted drug delivery; the positive zeta potential allowed
an effective cellular uptake and the polyethylenimine amine groups facilitate the
endosomal escape quickly. The distribution and pharmacodynamics of PPP-RH-NPs
were studied in a streptozocin-induced DN model, which explicitly demonstrated
kidney-targeted distribution and improved the therapeutic effects of RH on DN by
ameliorating several pathological indicators. Conclusion: Therefore, this study
not only stimulates further clinical research on RH but also, more importantly,
proposes a promising DN therapy consisting of an effective kidney-targeted drug
delivery.
PMID- 29950833
TI - Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock
proteins: insights from mathematical modeling.
AB - Background: Nano-therapeutic utilizing hyperthermia therapy in combination with
chemotherapy, surgery, and radiation is known to treat various types of cancer.
These cancer treatments normally focus on reducing tumor burden. Nevertheless, it
is still challenging to confine adequate thermal energy in a tumor and obtain a
complete tumor ablation to avoid recurrence and metastasis while leaving normal
tissues unaffected. Consequently, it is critical to attain an alternative tumor
killing mechanism to circumvent these challenges. Studies have demonstrated that
extracellular heat shock proteins (HSPs) activate antitumor immunity during tumor
cell necrosis. Such induced immunity was further shown to assist in regressing
tumor and reducing recurrence and metastasis. However, only a narrow range of
thermal dose is reported to be able to acquire the optimal antitumor immune
outcome. Consequently, it is crucial to understand how extracellular HSPs are
generated. Materials and methods: In this work, a predictive model integrating
HSP synthesis mechanism and cell death model is proposed to elucidate the HSP
involvement in hyperthermia cancer immune therapy and its relation with dead
tumor cells. This new model aims to provide insights into the thermally released
extracellular HSPs by dead tumor cells for a more extensive set of conditions,
including various temperatures and heating duration time. Results: Our model is
capable of predicting the optimal thermal parameters to generate maximum HSPs for
stimulating antitumor immunity, promoting tumor regression, and reducing
metastasis. The obtained nonlinear relation between extracellular HSP
concentration and increased dead cell number, along with rising temperature,
shows that only a narrow range of thermal dose is able to generate the optimal
antitumor immune result. Conclusion: Our predictive model is capable of
predicting the optimal temperature and exposure time to generate HSPs involved in
the antitumor immune activation, with a goal to promote tumor regression and
reduce metastasis.
PMID- 29950834
TI - Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human
colorectal cancer cell line LS180 to megavoltage radiation.
AB - Background: This study investigated the effectiveness and underpinning mechanisms
of radiosensitization using octaarginine (R8)-modified gold nanoparticle
poly(ethylene glycol) (GNP-PEG-R8) in colorectal cancer cell line LS180 to
megavoltage radiotherapy in vitro. Method: In-house synthesized GNP-PEG was
characterized by transmission electron microscopy, dynamic light scattering,
ultraviolet-visible spectrophotometry, and X-ray photoelectron spectroscopy.
Inductively coupled plasma mass spectroscopy was used to quantify
internalization. Direct cytotoxicity was established using the Cell Counting Kit
8, while radiosensitivity was determined using the gold standard in vitro
clonogenic assay. Cell-cycle distribution, apoptosis, reactive oxygen species
(ROS), and mitochondrial membrane potential (MMP) were analyzed by flow
cytometry, further exploring the key mechanisms driving GNP-PEG-R8
radiosensitization. Results: The core GNP diameter was 6.3+/-1.1 nm (mean+/-SD).
Following functionalization, the hydrodynamic diameter increased to 19.7+/-2.8 nm
and 27.8+/-1.8 nm for GNP-PEG and GNP-PEG-R8, with respective surface plasmon
resonance peaks of 515 nm and 525 nm. Furthermore, incorporation of the R8
significantly increased nanoparticle internalization compared to GNP-PEG
(p<0.001) over a 1 h treatment period. Functionalized GNPs confer little
cytotoxicity below 400 nM. In clonogenic assays, radiation combined with GNP-PEG
R8 induced a significant reduction in colony formation compared with radiation
alone, generating a sensitizer enhancement ratio of 1.59. Furthermore, GNP-PEG-R8
plus radiation predominantly induced cell-cycle arrest in the G2/M phase,
increasing G2/M stalling by an additional 10% over GNP-PEG, markedly promoting
apoptosis (p<0.001). Finally, ROS levels and alterations in MMP were
investigated, indicating a highly significant (p<0.001) change in both parameters
following the combined treatment of GNP-PEG-R8 and radiation over radiation
alone. Conclusion: R8-modified GNPs were efficiently internalized by LS180 cells,
exhibiting minimal cytotoxicity. This yielded significant radiosensitization in
response to megavoltage radiation. GNP-PEG-R8 may enhance radiosensitivity by
arresting cell cycle and inducing apoptosis, with elevated ROS identified as the
likely initiator.
PMID- 29950835
TI - X-ray radiation-induced and targeted photodynamic therapy with folic acid
conjugated biodegradable nanoconstructs.
AB - Introduction: The depth limitation of conventional photodynamic therapy (PDT)
with visible electromagnetic radiation represents a challenge for the treatment
of deep-seated tumors. Materials and methods: To overcome this issue, we
developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA)
polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin
(VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet
oxygen. The X-ray radiation used in this study allows this system to breakthrough
the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation
through biological tissue. In addition, the conjugation of our NPs with folic
acid moieties enables specific targeting of HCT116 cancer cells that overexpress
the folate receptors. We carried out physiochemical characterization of PLGA NPs,
such as size distribution, zeta potential, morphology and in vitro release of VP.
Cellular uptake activity and cell-killing effect of these NPs were also
evaluated. Results and discussion: Our results indicate that our nanoconstructs
triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the
radiation alone. We attributed the X-ray-induced singlet oxygen generation from
the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen
species generation facilitated by energetic secondary electrons produced in the
tissue. Conclusion: The cytotoxic effect caused by VP offers the possibility of
enhancing the radiation therapy commonly prescribed for the treatment of cancer
by simultaneous PDT.
PMID- 29950836
TI - Green synthesis of gold and silver nanoparticles from Cannabis sativa (industrial
hemp) and their capacity for biofilm inhibition.
AB - Background: Cannabis sativa (hemp) is a source of various biologically active
compounds, for instance, cannabinoids, terpenes and phenolic compounds, which
exhibit antibacterial, antifungal, anti-inflammatory and anticancer properties.
With the purpose of expanding the auxiliary application of C. sativa in the field
of bio-nanotechnology, we explored the plant for green and efficient synthesis of
gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs). Methods and results:
The nanoparticles were synthesized by utilizing an aqueous extract of C. sativa
stem separated into two different fractions (cortex and core [xylem part])
without any additional reducing, stabilizing and capping agents. In the synthesis
of AuNPs using the cortex enriched in bast fibers, fiber-AuNPs (F-AuNPs) were
achieved. When using the core part of the stem, which is enriched with phenolic
compounds such as alkaloids and cannabinoids, core-AuNPs (C-AuNPs) and core-AgNPs
(C-AgNPs) were formed. Synthesized nanoparticles were character-ized by UV
visible analysis, transmission electron microscopy, atomic force microscopy,
dynamic light scattering, Fourier transform infrared, and matrix-assisted laser
desorption/ionization time-of-flight. In addition, the stable nature of
nanoparticles has been shown by thermogravimetric analysis and inductively
coupled plasma mass spectrometry (ICP-MS). Finally, the AgNPs were explored for
the inhibition of Pseudomonas aeruginosa and Escherichia coli biofilms.
Conclusion: The synthesized nanoparticles were crystalline with an average
diameter between 12 and 18 nm for F-AuNPs and C-AuNPs and in the range of 20-40
nm for C-AgNPs. ICP-MS analysis revealed concentrations of synthesized
nanoparticles as 0.7, 4.5 and 3.6 mg/mL for F-AuNPs, C-AuNPs and C-AgNPs,
respectively. Fourier transform infrared spectroscopy revealed the presence of
flavonoids, cannabinoids, terpenes and phenols on the nanoparticle surface, which
could be responsible for reducing the salts to nanoparticles and further
stabilizing them. In addition, the stable nature of synthesized nanoparticles has
been shown by thermogravimetric analysis and ICP-MS. Finally, the AgNPs were
explored for the inhibition of P. aeruginosa and E. coli biofilms. The
nanoparticles exhibited minimum inhibitory concentration values of 6.25 and 5
ug/mL and minimum bactericidal concentration values of 12.5 and 25 ug/mL against
P. aeruginosa and E. coli, respectively.
PMID- 29950837
TI - Silica nanoparticle exposure during the neonatal period impairs hippocampal
precursor proliferation and social behavior later in life.
AB - Introduction: Silica nanoparticles (SiO2-NPs) are currently among the most widely
used nanomaterials, but their potentially adverse effects on brain development
remain unknown. The developing brain is extremely sensitive to NP neurotoxicity
during the early postnatal period. Materials and methods: Herein, we investigated
the effects of SiO2-NPs (doses of 10, 20, or 50 mg with a particle size of ~91
nm, equivalent to aerosol mass concentrations 55.56, 111.11, and 277.78 mg/m3,
respectively) exposure from postnatal day (P) 1 to P7 on hippocampal precursor
proliferation at P8 and long-term neurobehavior in adults. Results: SiO2-NP
exposure resulted in inflammatory cell infiltration in lung tissue, microglia
over-activation in the hippocampal dentate gyrus (DG), and decreased hippocampal
precursor proliferation in the DG-subgranular zone at P8. Moreover, after
exposure to 20 mg of SiO2-NPs, mice exhibited social interaction deficits and
slight anxiety-like behaviors in adulthood, but this exposure did not induce
locomotor activity impairment, depression-like behavior, or short-term memory
impairment. Discussion: These findings suggest that early-age SiO2-NP exposure
induced inflammation and inhibited precursor proliferation in the DG in a dose
dependent manner, which might be related to the social dysfunction observed in
adulthood.
PMID- 29950838
TI - Influence of dose, gender, and cigarette smoking on clozapine plasma
concentrations.
AB - Introduction: Therapeutic drug monitoring (TDM) of clozapine is a very useful
method for verifying both the correct intake and the interindividual variability
of its metabolism, thereby avoiding the risk of toxicity. The purposes of this
paper were to discover how many patients using clozapine in common clinical
practice have clozapine plasma concentration (PC) levels in the proposed
reference range and to identify factors that influence clozapine PC levels.
Methods: Our study included 100 inpatients (diagnosed with schizophrenia or
schizoaffective disorder) taking standard doses of clozapine (100-700 mg/day).
Clozapine concentration was measured by high-performance liquid chromatography.
Correlations between doses and PC levels and the influence of smoking and gender
on clozapine PC levels were calculated. Results: A large number of the patients
(67%) had PC levels outside the proposed reference range. The clozapine PC levels
were influenced by dose, gender, and cigarette smoking. Conclusion: The
correlations between dose, gender, and cigarette smoking and clozapine PC levels
highlighted by our study overlap other research. It was surprising to find such a
large number of patients with clozapine PC levels outside the therapeutic range.
This result suggests the importance of clozapine TDM due to misunderstood inter-
and/or intraindividual variability or misestimated partial therapeutic
compliance.
PMID- 29950839
TI - Systematic literature review on patterns of pharmacological treatment and
adherence among patients with bipolar disorder type I in the USA.
AB - Background: Bipolar disorder type I (BD-I) is a chronic condition characterized
by mania episodes followed by syndromic recovery periods, usually permeated by
depressive symptoma-tology and recurring acute manic episodes. It requires long
term pharmacological treatment; thus, it is critical to understand the patterns
of drug therapy use and medication compliance to better plan health care policies
and needs. This systematic literature review aims to study these data among
patients with BD-I in the USA, focusing on medications to treat mania. Methods:
Articles published in the last 10 years to October 2016 were searched on MEDLINE
and Embase. Studies on patterns of drug therapy, concordance of prescription with
clinical practice guidelines, and adherence and persistence with pharmacological
treatments for BD-I in the USA under observational conditions, with focus on
treatments for mania, were selected. Results: Treatment prevalence for BD-I is
low in the USA, with the most current study showing a 46% 12-month rate. There is
a lack of studies addressing the use of long-acting injectable (LAI)
antipsychotics. Second-generation antipsychotics (SGAs) have been used by nearly
all patients receiving oral antipsychotics since the 2000s. However, 30%-60% of
individuals with BD do not receive appropriate treatment, and adherence to oral
therapies is poor, with medication possession ratios >=80% seen in only
approximately 60% of patients. For persistence rates, results suggest that
treatment duration is short for a condition with recommendation for at least 6
months of maintenance therapy. Literature indicates that LAI SGAs may be related
to better adherence and persistence. Conclusion: There is a need for studies
addressing specifically patterns of therapy and adherence to pharmacological
treatment in BD-I patients in the USA to better understand the value of current
standards, and an urgent need to improve the rates of adherence and persistence
to BD-I pharmacotherapy and to increase the understanding of LAI SGAs' potential
to address this issue.
PMID- 29950840
TI - Effects of sequential nutritional support on nutritional status and expression of
regulatory T lymphocyte in patients with early severe traumatic brain injury.
AB - Objective: To investigate the effects of sequential nutritional support on
nutritional status and immune regulation in patients with early severe traumatic
brain injury (STBI). Patients and methods: A total of 62 patients diagnosed with
STBI enrolled from Chaoyang Hospital (Beijing, China) from February 2015 to
October 2016 were divided into two groups. The observational group (n=34) was
given sequential nutritional support and the control group (n=28) was given the
standard formula of whole protein enteral preparations. The energy supply for the
two groups was 30 kcal/kg/d and protein 1.6 g/kg/d, respectively. The albumin
(ALB), total protein (TP), high-sensitivity C-reactive protein (Hs-CRP), neuron
specific enolase (NSE), Glasgow Coma Score (GCS), and regulatory T cells before
and after nutritional treatment were measured in both groups. Results: At the
14th day, the levels of ALB (41.7+/-4.2 g/L) and TP (70.6+/-4.9 g/L) were
significantly higher than those in the control group (33.5+/-2.3 g/L and 62.3+/
3.9 g/L) (P<0.05). The levels of Hs-CRP and NSE were significantly lower in the
observational group (0.96+/-0.82 mg/L and 11.96+/-7.82 ng/L) than in the control
group (1.17+/-0.74 mg/L and 19.17+/-6.74 ng/L) (P<0.05). The GCS score in the
observational group (11.5+/-2.9) was significantly higher than that in the
control group (8.1+/-1.7) (P<0.05). The percentage of Tregs in the peripheral
CD4+ lymphocytes was significantly lower in the observational group than in the
control group (P<0.05). Conclusion: The effect of sequential nutritional support
is better than conventional nutritional support in patients with STBI. The
findings call for early identification of malnutrition and individual nutritional
support.
PMID- 29950842
TI - Mindfulness-based cognitive therapy in patients with depression: current
perspectives.
AB - Mindfulness-based cognitive therapy (MBCT) was developed to prevent relapse in
individuals with depressive disorders. This widely used intervention has garnered
considerable attention and a comprehensive review of current trends is warranted.
As such, this review provides an overview of efficacy, mechanisms of action, and
concludes with a discussion of dissemination. Results provided strong support for
the efficacy of MBCT despite some methodological shortcomings in the reviewed
literature. With respect to mechanisms of action, specific elements, such as
mindfulness, repetitive negative thinking, self-compassion and affect, and
cognitive reactivity have emerged as important mechanisms of change. Finally,
despite a lack of widespread MBCT availability outside urban areas, research has
shown that self-help variations are promising. Combined with findings that
teacher competence may not be a significant predictor of treatment outcome, there
are important implications for dissemination. Taken together, this review shows
that while MBCT is an effective treatment for depression, continued research in
the areas of efficacy, mechanisms of action, and dissemination are recommended.
PMID- 29950841
TI - Early antipsychotic treatment in juvenile rats elicits long-term alterations to
the adult serotonin receptors.
AB - Background: Antipsychotic drug (APD) prescription/use in children has increased
significantly worldwide, despite limited insight into potential long-term effects
of treatment on adult brain functioning. While initial long-term studies have
uncovered alterations to behaviors following early APD treatment, further
investigations into potential changes to receptor density levels of related
neurotransmitter (NT) systems are required. Methods: The current investigation
utilized an animal model for early APD treatment with aripiprazole, olanzapine,
and risperidone in male and female juvenile rats to investigate potential long
term changes to the adult serotonin (5-HT) NT system. Levels of 5-HT1A, 5-HT2A,
and 5-HT2C receptors were measured in the prefrontal cortex (PFC), caudate
putamen (CPu), nucleus accumbens (NAc), and hippocampus via Western Blot and
receptor autoradiography. Results: In the male cohort, long-term changes to 5
HT2A and 5-HT2C receptors were found mostly across hippocampal and cortical brain
regions following early aripiprazole and olanzapine treatment, while early
risperidone treatment changed 5-HT1A receptor levels in the NAc and PFC. Lesser
effects were uncovered in the female cohort with aripiprazole, olanzapine and
risperidone to alter 5-HT1A and 5-HT2A receptors in NAc and hippocampal brain
regions, respectively. Conclusion: The results of this study suggest that early
treatment of various APDs in juvenile rats may cause gender and brain regional
specific changes in 5-HT2A and 5-HT2C receptors in the adult brain.
PMID- 29950843
TI - Vibration therapy in patients with cerebral palsy: a systematic review.
AB - The neurological disorder cerebral palsy (CP) is caused by unprogressive lesions
of the immature brain and affects movement, posture, and the musculoskeletal
system. Vibration therapy (VT) is increasingly used to reduce the signs and
symptoms associated with this developmental disability. The purpose of this
narrative review was systematically to appraise published research regarding
acute and long-term effects of VT on functional, neuromuscular, and structural
parameters. Systematic searches of three electronic databases identified 28
studies that fulfilled the inclusion criteria. Studies were analyzed to determine
participant characteristics, VT-treatment protocols, effect on gross motor
function (GMF), strength, gait, posture, mobility, spasticity, reflex
excitability, muscle tone, mass, and bone strength within this population, and
outcome measures used to evaluate effects. The results revealed that one acute
session of VT reduces reflex excitability, spasticity, and coordination deficits.
Subsequently, VT has a positive effect on the ability to move, manifested for
GMF, strength, gait, and mobility in patients with CP. Effects persist up to 30
minutes after VT. Long-term effects of VT manifest as reduced muscle tone and
spasticity occurring concomitantly with improved movement ability in regard to
GMF, strength, gait, and mobility, as well as increased muscle mass and bone
mineral density. Posture control remained unaffected by VT. In conclusion, the
acute and chronic application of VT as a nonpharmacological approach has the
potential to ameliorate CP symptoms, achieving functional and structural
adaptations associated with significant improvements in daily living. Even though
further studies including adult populations validating the neuromuscular
mechanisms underlying the aforementioned adaptations should be fostered, growing
scientific evidence supports the effectiveness of VT in regard to supplementing
conventional treatments (physiotherapy and drugs). Therefore, VT could reduce CP
associated physical disability and sensorimotor handicaps. Goals for patients and
their caregivers referring to greater independence and improved safety may be
achieved more easily and time efficiently.
PMID- 29950844
TI - The role of MAPT gene in Chinese dementia patients: a P301L pedigree study and
brief literature review.
AB - Background and purpose: Frontotemporal dementia (FTD) is the second most common
presenile dementia characterized by behavioral changes and language impairment.
The diagnosis of FTD relies heavily on neuroimaging, and sometimes on genetic
screening. However, the genetic components in Chinese FTD patients remain largely
unknown. Only a few FTD cases with established mutations have been reported in
China. This study reported the detailed clinical and neuroimaging features in a
Chinese behavioral variant FTD family. The role of MAPT gene mutation in Chinese
dementia patients was also reviewed. Methods: By detailed inquiry of all affected
individuals in the family, this study summarized the main clinical features of
the disease. Four candidate genes (MAPT, PSEN1, PSEN2, and APP) were screened by
direct sequencing. Structural magnetic resonance imaging (MRI), functional
imaging of cerebral blood flow with arterial spin-labeled MRI (ASL-MRI), and
cerebral metabolism with fluorodeoxyglucose positron emission tomography (FDG
PET) were collected in the proband and healthy mutation carriers. Results: By
direct sequencing of candidate genes (MAPT, PSEN1, PSEN2, and APP), this study
identified the P301L mutation in the MAPT gene in the proband and three
unaffected family members. The phenotype of the affected cases was consistent
within the pedigree. In this genetically proven behavioral variant FTD (bvFTD)
patient, the maps of hypoperfusion on ASL-MRI look fairly similar to the
hypometabolism on FDG-PET. The clinical feature for this bvFTD was in line with
the hypoperfusion or hypometabolism pattern on functional neuroimagings. The
phenotype of P301L in east Asia seems similar to western countries. Conclusion:
For the inherited FTD patients, ASL-MRI and genetic identification were strongly
recommended for the final diagnosis. In case of being underestimated, the role of
MAPT gene mutation in Chinese FTD patients warrants further investigation.
PMID- 29950845
TI - The detection of white matter alterations in obsessive-compulsive disorder
revealed by TRActs Constrained by UnderLying Anatomy (TRACULA).
AB - Purpose: In recent years, a large number of studies have investigated obsessive
compulsive disorder (OCD) using diffusion-weighted images (DWIs) and have
reported microstructural abnormalities in various regions, mainly the corpus
callosum and cingulum. In the present study, we aimed to detect microstructural
changes in the white matter using whole-brain tractography. Patients and methods:
We obtained MRI data from 25 adult non-medicated OCD patients and 27 healthy
controls. DWI data from MRI scans were analyzed by the automated probabilistic
tractography method referred to as TRActs Constrained by UnderLying Anatomy
(TRACULA). We investigated diffusivity parameters: fractional anisotropy, radial
diffusivity (RD), axial diffusivity, and mean diffusivity in 18 major white
matter tracts and examined indices to know which measurements in which fibers can
predict the diagnosis of OCD. Results: Compared to healthy controls, OCD patients
had significantly increased RD in the forceps major and a reduction of RD in the
right cingulum angular (infracallosal) bundle. There was no correlation between
these values and the clinical features. Conclusion: We found RD alterations in
the forceps major and the right cingulum angular (infracallosal) bundle, which
might be associated with myelination changes in the temporal and occipital
regions in OCD. Our results suggest that the pathogenesis of OCD may include
abonormality of myelination status in not only the fronto-striato-thalamic
circuit but also the posterior and temporal regions.
PMID- 29950847
TI - COMT Val 108/158 Met polymorphism and treatment response to aripiprazole in
patients with acute schizophrenia.
AB - Introduction: The COMT Val 108/158 Met polymorphism (rs4680) may affect treatment
response to antipsychotics, as well as metabolism and dynamics of
neurotransmitters during the treatment of schizophrenia. We investigated the
effects of the COMT Val 108/158 Met polymorphism on treatment response to
aripiprazole and plasma monoamine metabolite levels in patients with acute
schizophrenia. Materials and methods: Forty patients with schizophrenia were
treated with aripiprazole for 6 weeks. We measured Positive and Negative Syndrome
Scale (PANSS) and plasma levels of homovanillic acid (HVA) and plasma MHPG (3
methoxy-4-hydroxyphenethyleneglycol) at baseline and endpoint. The COMT Val
108/158 Met polymorphism was genotyped with the polymerase chain reaction and
restriction fragment length polymorphism. Results: There were significant
genotype-time interactions on PANSS total and general psychopathology scores,
with Met/Met genotype showing greater improvement. The response rate to
aripiprazole did not differ between COMT Val 108/158 Met genotype groups. We
found a significant time effect on plasma MHPG levels, but no time effect on
plasma HVA levels or time-genotype interactions in the plasma levels of HVA and
MHPG. Although the responder rate did not differ among the 3 genotype groups.
Conclusion: Our results suggest that individuals with the Met/Met genotype had
greater improvement in PANSS score after the treatment with aripiprazole. On the
other hand, the Val 108/158 Met polymorphism may not induce changes in plasma
levels of monoamine metabolites during aripiprazole treatment. Because of the
small sample size, further studies are needed to confirm and to extend our
results.
PMID- 29950846
TI - Head-to-head comparison of 1-year aripiprazole long-acting injectable (LAI)
versus paliperidone LAI in comorbid psychosis and substance use disorder: impact
on clinical status, substance craving, and quality of life.
AB - Background: To overcome nonadherence in patients with psychosis switch to long
acting injectable (LAI) antipsychotic formulations is adopted. Most oral versus
LAI comparisons showed similar antipsychotic responses. Psychoses often overlap
with substance use disorder (SUD). Head-to-head LAI comparisons have hitherto
focused only on non-comorbid populations. Objective: The objective of this study
was to compare two LAIs, administered for 12 months, in initially hospitalized
patients with psychosis comorbid with SUD in their clinical and quality of life
(QoL) outcomes. Patients and methods: Inpatients were recruited during 2016 and
switched randomly to 400 mg intramuscular aripiprazole monohydrate (AM) (N=50) or
to 100 mg intramuscular paliperidone palmitate (PP) once-monthly (N=51); patients
were discharged and followed up for 12 months. Patients were rated at baseline
and after 1 year through the Clinical Global Impression scale - severity (CGIs),
substance craving intensity was rated through a visual analog scale for substance
craving, and QoL through the World Health Organization (WHOQOL-BREF) scale. We
addressed confounders with backward stepwise logistic regression and three-way
analysis of variance. Results: PP were older and had more cases of schizophrenia
spectrum and less bipolar disorders than AM, but AM had a stronger craving for
substances at baseline. Both LAIs were associated with significant improvements
in all outcomes, with AM displaying stronger effect sizes than PP. The two groups
did not differ on baseline WHOQOL-BREF scores in any domain, but at the 1-year
follow-up, AM fared better on all domains. The two groups did not differ in final
severity, but PP scored higher than AM in craving at the 1-year
endpoint.Limitation: The CGIs is not a refined tool for severity and the
substance craving may be subject to recall bias. Conclusion: 1-year AM and PP was
followed by improved clinical status and QoL and reduced substance craving in a
population with psychosis and SUD comorbidity. AM, compared to PP, improved
craving and QoL at the 1-year follow-up.
PMID- 29950848
TI - Neuropsychiatric assessments in patients with multiple sclerosis in early phases
and with low disability.
AB - Background: In the early phases of multiple sclerosis (MS), patients exhibit
slight neuropsychiatric deficits that can only be detected using reliable tools.
Aim: The present investigation aimed to examine neuropsychological performance in
35 patients with incipient MS. Patients and methods: For the MS group, the
inclusion criteria included time of disease <3 years and low disability. The
neuropsychological battery consisted of Rey Auditory Learning Test, Controlled
Oral Word Association Test, Hooper Visual Organization Test, and Symbol Digit
Modalities Test (SDMT). Results: After correction for the educational level, no
significant effect of MS on performance was found for all the tests except for
the number of errors of the SDMT (NE-SDMT). Higher levels of education were
associated with better performances in all tests, except for the NE-SDMT. MS
patients made more errors than the controls. Conclusion: The effect on the NE
SDMT may reflect difficulties in the ability to inhibit inadequate responses.
Patients may exhibit impulsive control disorders in incipient MS, independent of
their educational level.
PMID- 29950849
TI - Factors associated with union time of acute middle-third scaphoid fractures: an
observational study.
AB - Background: The aim of this study was to investigate the union time of acute
middle-third scaphoid fractures following treatments and to analyze the effect of
different factors on late union. Patients and methods: We retrospectively
reviewed patients with acute middle-third scaphoid fracture at our institution
between January 2013 and December 2017. Patient demographics, fracture
characteristics, and treatment strategy, such as age, gender, body mass index,
habit of smoking, sides of injury, dominant hand, ulnar variance, multiple
fractures, and treatment methods, were investigated. Univariate and multivariate
analyses were used to identify possible predictive factors. Results: A total of
132 patients with scaphoid fracture were included in our study. Operation was
performed in 67 patients (50.8%), and conservative treatment was performed in the
other 65 patients (49.2%). The union time was 7.2+/-0.5 weeks. In the
multivariate logistic regression analysis, late diagnosis (odds ratio, 1.247; 95%
CI, 1.022-1.521) and conservative treatment method (odds ratio, 1.615; 95% CI,
1.031-2.528) were identified as 2 independent predictors of late union in
scaphoid fractures patients. Other parameters were not demonstrated to be
predictive factors. Conclusion: Late diagnosis and conservative treatment were
two factors associated with late union. Long time of follow-up is necessary for
patient with these factors.
PMID- 29950850
TI - Successful treatment for acute prosthetic joint infection due to MRSA and Candida
albicans: a case report and literature review.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) and Candidal prosthetic joint
infections (PJIs) are very rare, and the optimal management for these patients is
still unknown. A 54-year-old man with traumatic arthritis due to previous
electric injury successfully retained the implant despite the successive
infection with MRSA and Candida albicans after total knee arthroplasty (TKA).
Continuous lavage with vancomycin was used to control MRSA infection and repeated
local washout plus oral swallow with voriconazole tablet were administered to
eradicate C. albicans. Additional three reported cases were identified by the
criteria of selecting patients with concomitant and/or successive MRSA and
Candidal PJIs. Different methods were applied with variable outcomes. Therefore,
several risk factors such as intra-articular corticosteroid injection, high
frequency of door openings in the operating room, excessive blood loss and
allogeneic red blood cell transfusions should be avoided. Debridement,
antibiotics and implant retention (DAIR) can be an alternative in dedicated
patients to control acute MRSA and Candidal PJIs. Particularly, repeated intra
articular washout with susceptible drugs and a prolonged duration of oral
antibiotics was essential for microbial control.
PMID- 29950851
TI - Gynecological emergency ultrasound in daytime and at night: differences that
cannot be ignored.
AB - Background: Ultrasonography, the preferred adjunct examination method and the
differential diagnostic tool for gynecologic emergency, can reflect the change
pattern of gynecological diseases in daytime and at night. The purpose of this
study was to analyze the diseases through gynecological emergency ultrasound in
daytime and at night and to evaluate the day-night difference in the accuracy of
ultrasound diagnosis. Materials and methods: Retrospective analysis was performed
on the 2016 clinical data of the patients who had undergone gynecological
emergency ultrasound at The First Affiliated Hospital of Guangxi Medical
University, and the results of the ultrasound diagnosis were compared with the
clinical diagnosis. Results: The following categories of gynecologic emergency
diseases during the daytime and at night have significant statistical differences
in the constituent ratio (P<0.001); ectopic pregnancy, intrauterine pregnancy,
acute pelvic inflammatory disease, no organic lesion in uterine and adnexa; while
the constituent ratio of abortion and trophoblastic diseases, ovarian tumor,
uterine and endometrial lesions, was no statistical difference during the daytime
and at night (P>0.05). The overall coincidence rate of ultrasound diagnosis was
96.3% (daytime, 97.9%; night, 86.4%). The coincidence rates of ectopic pregnancy
ultrasonography diagnosis in daytime and at night were 96.4 and 75.4%,
respectively; the difference was statistically significant (P<0.001). Conclusion:
Since the different constituent ratio of disease between daytime and night
gynecological emergency ultrasound was significantly different, and the
diagnostic accuracy of ultrasound at night was low; hence, the ultrasound doctor
at night should pay attention to improve the accuracy of diagnosis and the
ability of differential diagnosis of ectopic pregnancy, and it is suggested that
some suspected cases during the night should be reexamined again in the daytime
to eliminate the errors resulted from subjective factors.
PMID- 29950852
TI - Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and
clinical relevance.
AB - Paraoxonase-1 (PON1) is a high-density lipoprotein-associated esterase and is
speculated to play a role in several human diseases including diabetes mellitus
and atherosclerosis. Low PON1 activity has been associated with increased risk of
major cardiovascular events, therefore a variety of studies have been conducted
to establish the cardioprotective properties and clinical relevance of PON1. The
major aim of this review was to highlight the important studies and to
subsequently assess if PON1 has clinical relevance. A review of the literature
showed that there is currently insufficient data to suggest that PON1 has
clinical relevance. It is our opinion that robust studies are required to clarify
the clinical relevance of PON1.
PMID- 29950853
TI - Not enough time for research? Use of supported funding to promote allied health
research activity.
AB - Purpose: The current project evaluated the impact of a short-term, supported
funding initiative that allowed staff from allied health (AH) professions to
undertake research activity within rostered employment time. Specifically, the
project will report on outcomes pertaining to individual research capacity,
research output, and overall satisfaction with the initiative. Participants and
methods: Sixteen AH clinicians (n=16) from six AH professions participated in the
evaluation of the initiative, with data being collected within a service
improvement framework. Clinicians received up to 4 weeks of protected time
relieved from their clinical duties to undertake research activities, including
writing for publication, undertaking a systematic review, data analysis, and
preparation of ethics applications. An AH Research Fellow provided additional
support and mentorship, including the development of an implementation plan.
Evaluation included pre-post measures of individual research capacity using a 15
item self-report Research Capacity and Culture (RCC) survey, a post
implementation satisfaction survey, and monitoring of research output achieved.
Results: Statistically significant improvements (p<0.05) were found on 14 out of
15 items on the RCC tool, with meaningful improvements in securing funding,
analyzing qualitative data, writing for publication, literature searching skills,
and providing advice to less experienced researchers. Overall satisfaction with
the initiative was high, with positive comments from AH professionals (AHPs)
regarding the initiative. Research output arising from the initiative included
eleven manuscripts being submitted, with six currently in publication and others
under review. Conclusion: The preliminary findings support the feasibility of
implementing a local, clinical funding model to promote individual research
capacity and research output for AHPs. The short-term funding should be supported
by local mentorship and guidance. Local barriers and suggestions to optimize
implementation, including integrating within existing research infrastructure and
using flexible "backfill" options, will also be described.
PMID- 29950854
TI - Association between common polymorphisms in ERCC gene and prognosis of
osteosarcoma in patients treated with chemotherapy: a meta-analysis.
AB - Purpose: Some previous studies have sought to investigate the roles of excision
repair cross complementation group 1 (ERCC1), ERCC2, ERCC4, and ERCC5 gene
polymorphisms in the prognosis of osteosarcoma patients. However, their results
were inconclusive. Here, we performed a meta-analysis to determine the strength
of the association between eight polymorphisms in the ERCC genes (rs11615,
rs3212986, rs2298881, rs13181, rs1799793, rs1800067, rs2296147, and rs1047768)
and prognosis of osteosarcoma patients treated with chemotherapy. Materials and
methods: We retrieved the relevant studies from PubMed, Embase, and Web of
Science in human osteosarcoma published prior to July 2017. Primary outcomes
included overall survival (OS) and event-free survival, expressed by hazard
ratios (HRs) with their corresponding 95% CIs. STATA software (version 12.0) was
utilized to perform data synthesis. Results: A total of 13 eligible follow-up
studies involving 2,303 patients met all the inclusion criteria, conducted in two
populations of ethnic descent: 11 Asians and two Caucasians. In the present meta
analysis, we demonstrated that the homozygous variant genotypes in ERCC2
rs1799793 and ERCC5 rs2296147 were significantly associated with OS in
osteosarcoma (TT vs GG for rs1799793: HR = 0.62, 95% CI = 0.41-0.93,
Pheterogeneity = 0.310, I2 = 15.3%, P = 0.020; TT vs CC for rs2296147: HR = 0.42,
95% CI = 0.23-0.78, Pheterogeneity = 0.708, I2 = 0.0%, P = 0.006). In addition,
no evidence of association was observed between prognosis in osteosarcoma and
ERCC1 rs11615, ERCC1 rs3212986, ERCC1 rs2298881, ERCC2 rs13181, ERCC4 rs1800067,
and ERCC5 rs1047768 polymorphisms. Conclusion: Our meta-analysis indicated that
TT genotype in the ERCC2 rs1799793 and ERCC5 rs2296147 might prolong the survival
time of patients with osteosarcoma, suggesting that the rs1799793 and rs2296147
polymorphisms can be used as predictors for prognosis of osteosarcoma patients
treated with chemotherapy.
PMID- 29950855
TI - Combined small-cell lung carcinoma.
AB - Currently, studies assessing combined small-cell lung carcinoma (C-SCLC) are
relatively scarce and limited. Indeed the clinicopathological features,
treatment, and prognosis of patients with C-SCLC have not been fully determined.
The incidence of C-SCLC ranges from 5%-28% in different studies, which is related
to the specimen types used. The clinical features of C-SCLC are characterized by
the higher proportion of peripheral locations, earlier stage, and more
opportunity to experience surgery. Surgery is more important for earlier stage C
SCLC. There have been no recent changes in the chemotherapy of C-SCLC, which is
recommended by the treatment guidelines for SCLC, neither showing survival
benefit from the 3-agent regimen. Meanwhile, the efficacy of epidermal growth
factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutated C-SCLC
patients remains inconclusive. This review focuses on clinical and pathologic
features, prognostic factors, and optimized treatment model in C-SCLC.
PMID- 29950856
TI - The prognosis for patients with newly diagnosed glioblastoma receiving
bevacizumab combination therapy: a meta-analysis.
AB - Background: A combination of temozolomide (TMZ) and radiotherapy and subsequent
adjuvant chemotherapy is the gold standard of treatment for glioblastoma (GB).
Bevacizumab (BEV), a humanized monoclonal antibody that blocks the effects of
vascular endothelial growth factor A, has produced impressive response rates for
recurrent GB and has been approved as second-line therapy. The efficacy and
safety of BEV in newly diagnosed GB are not known. Aim: This systematic meta
analysis was undertaken to evaluate the value of combination therapy involving
BEV in newly diagnosed GB. Methods: Electronic databases were searched for
eligible literature up to October 2017. Randomized controlled trials assessing
the efficacy and safety of BEV in patients with newly diagnosed GB were included,
of which the main outcomes were progression-free survival (PFS), overall survival
(OS), and adverse events (AEs). All the data were pooled with the corresponding
95% confidence intervals (CIs) using RevMan software. Sensitivity analyses and
heterogeneity were quantitatively evaluated. Results: A total of six randomized
controlled trials were included in this analysis. The experimental BEV group had
significantly improved the overall PFS (OR =0.46, 95% CI =0.26-0.81, P=0.007), as
well as PFS at 6 months (OR =3.47, 95% CI =2.85-4.22, P<0.00001) and PFS at 12
months (OR =2.02, 95% CI =1.66-2.46, P<0.00001), respectively. However, there
were no significant differences in PFS at 24 months with BEV (OR =0.95, 95% CI
=0.61-1.48, P=0.82). OS at 6 months (P=0.07) and 24 months (P=0.07) was not
significantly improved with BEV in patients with newly diagnosed GB. However, the
meta-analysis on the OS at 12 months showed differences with BEV (OR =1.24, 95%
CI =1.03-1.50, P=0.02). Conclusion: Our study indicates that addition of BEV for
newly diagnosed GB resulted in a superior PFS rate. However, the combination
therapy involving BEV did not improve OS. Future investigations are needed to
analyze whether BEV helps improve OS efficacy.
PMID- 29950857
TI - Curcumin suppresses the progression of laryngeal squamous cell carcinoma through
the upregulation of miR-145 and inhibition of the PI3K/Akt/mTOR pathway.
AB - Background: Curcumin is a polyphenol extracted from the rhizomes of Curcuma longa
with extensive biological and pharmacological effects. The present study aimed to
investigate the mechanisms of curcumin in laryngeal squamous cell carcinoma
(LSCC). Methods: Quantitative real-time reverse transcriptase-polymerase chain
reaction was performed to detect the expressions of miR-145 in LSCC tissues and
cells. The effects of miR-145 and curcumin on cell proliferation, apoptosis, cell
cycle, migration and invasion were explored by MTT assay, flow cytometry
analysis, Transwell migration and invasion assay, respectively. The effects of
miR-145 combined with curcumin on the phosphoinositol 1,3 kinase (PI3K)/protein
kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were detected by
Western blot analysis. Results: miR-145 was significantly downregulated in LSCC
tissues and cells. Curcumin administration upregulated miR-145 expression in LSCC
cells in a dose-dependent manner. miR-145 overexpression and curcumin treatment
both markedly suppressed cell proliferation, migration and invasion and induced
cell cycle arrest and apoptosis in LSCC cells. Moreover, curcumin treatment
reversed the enhanced effects on cell viability, migration and invasion and the
inhibitory effects on apoptosis conferred by anti-miR-145 in LSCC cells. Curcumin
treatment dramatically aggravated miR-145-induced inhibition of the PI3K/Akt/mTOR
pathway and reversed anti-miR-145-mediated activation of the PI3K/Akt/mTOR
pathway in LSCC cells. Conclusion: Curcumin suppressed LSCC progression through
the upregulation of miR-145 and inhibition of the PI3K/Akt/mTOR pathway.
PMID- 29950858
TI - Multiple biological functions of transcription factor 21 in the development of
various cancers.
AB - Transcription factor 21 (TCF21) is a basic helix-loop-helix transcription factor
that binds to DNA and regulates cell differentiation and cell fate specification
through mesenchymal-epithelial transition during development. The TCF21 gene is
epigenetically inactivated in many types of human cancers and exerts a wide
variety of functions, including the regulation of epithelial-mesenchymal
transition, invasion, metastasis, cell cycle, and autophagy. This review focuses
on research progress in relation to the roles of TCF21 in tumor development. We
systematically consider multiple pathological functions of TCF21 in various
cancers, revealing the molecular bases of its diverse biological roles and
providing new directions for future research.
PMID- 29950859
TI - Prognostic value of miR-17-5p in cancers: a meta-analysis.
AB - Background: Studies have shown that miR-17-5p plays an important role in the
development of cancer. The aim of this meta-analysis was to quantitatively
analyze the association of miR-17-5p with prognosis in various cancers. Materials
and methods: We searched the PubMed, EMBASE, Web of Science, and Cochrane library
databases for relevant studies through August 2017. The prognostic data and
clinico-pathological features of overall survival (OS) and disease-free survival
(DFS) were extracted to investigate the association between miR-17-5p expression
and tumor prognosis. In addition, odds ratios (ORs) were used to assess the
correlations between miR-17-5p expression and clinicopathological
characteristics. Results: A total of ten studies were incorporated into this
systematic review, and we found that high miR-17-5p expression can predict poor
OS for malignancies (combined hazard ratio [HR]=1.87; 95% confidence interval
[CI], 1.37-2.55; P=0.000) as well as poor DFS (combined HR=1.60; 95% CI, 1.05
2.44; P=0.027). Further subgroup analyses suggested that high miR-17-5p
expression was related to poor OS in Asian patients (combined HR=1.92; 95% CI,
1.37-2.71; P=0.000) and the serum/plasma sample source subgroup (combined
HR=2.13; 95% CI, 1.36-3.31; P=0.001). The combined OR indicated that the
expression of miR-17-5p was associated with lymph node invasion (OR=1.28; 95% CI,
1.05-1.56; P=0.016) and venous invasion (OR=1.92; 95% CI, 1.40-2.63; P=0.000).
Conclusion: Elevated expression of miR-17-5p suggested a poor prognosis in cancer
patients and may serve as a new tumor marker to monitor cancer development and
progression.
PMID- 29950860
TI - The role of radioactive iodine therapy in papillary thyroid cancer: an
observational study based on SEER.
AB - Background: Papillary thyroid cancer (PTC) is a common endocrine malignancy with
relatively good prognosis. Radioactive iodine (RAI) is considered effective for
patients with total or nearly total thyroidectomy, but the beneficial effects of
RAI are still controversial. Materials and methods: To determine whether RAI
therapy could improve the survival rates of PTC patients, we conducted a
retrospective analysis using data from the National Cancer Institute's
Surveillance, Epidemiology, and End Results (SEER) program. Disease-specific
survival (DSS) was obtained using multivariate Cox proportional hazard
regressions. Results: DSS was improved by RAI ablation in patients with tumor >2
cm, age >45 years and gross extrathyroidal or lymph node metastasis. In a further
analysis, RAI therapy did not improve the DSS in patients with tumor <2 cm except
those with distant metastasis. For patients with tumor >2 cm, those involving
gross extrathyroidal extension, age >45 years or disease in the lymph nodes, DSS
was improved after RAI therapy. Patients with distant metastasis always benefited
from RAI ablation. Conclusion: RAI ablation should be recommended to patients
with tumor <2 cm and distant metastasis or patients with tumor >2 cm and one of
the following risk factors: gross extrathyroidal extension, age >45 years, lymph
node and distant metastases.
PMID- 29950861
TI - Clinicopathological and prognostic significance of FoxM1 in hepatocellular
carcinoma patients: a meta-analysis.
AB - Background and aims: Recently, the abnormal expression of FoxM1 has been found in
many malignant tumors. However, the clinicopathological and prognostic value of
FoxM1 expression in hepatocellular carcinoma (HCC) patients remains
controversial. We conducted a meta-analysis to establish the relationship between
FoxM1 expression and the clinicopathological features and prognostic value in
patients with HCC. Methods: An electronic search for relevant articles was
conducted according to a set of criteria in the PubMed, Cochrane Library, Web of
Science, EMBASE, Chinese CNKI and Chinese WanFang databases. The correlation data
between FoxM1 expression and clinicopathological features and survival outcomes
were analyzed. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were
calculated using STATA14.2. Results: A total of 14 studies comprising of 2,036
patients were enrolled in this meta-analysis. The results showed that FoxM1
expression was related to the incidence, tumor size (>5 cm), vascular invasion,
differentiation and TNM stage. Moreover, overexpression of FoxM1 indicated a poor
3- and 5-year overall survival rate (OS) and recurrence-free survival rate
(disease-free survival rate). Conclusion: Our meta-analysis indicated that FoxM1
expression was associated with incidence, tumor size (>5 cm), vascular invasion,
differentiation and TNM stage. Accordingly, FoxM1 may be a reliable prognostic
biomarker for patients with HCC. However, additional high-quality studies are
still needed to further support these findings.
PMID- 29950862
TI - Impact of RNA integrity and blood sample storage conditions on the gene
expression analysis.
AB - Background: The reliability of RNA sequencing (RNA-seq) output is affected by the
quality of RNAs, which is in turn dependent on the quality of samples. Therefore,
the purposes of this study were to reconsider the threshold of the RNA integrity
number (RIN) and propose a simple and efficient storage scheme of blood samples
for RNA-seq. Patients and methods: The RNAs were extracted from blood samples
that were stored at different conditions and used for sequencing. The
bioinformatic analyses were performed to evaluate the impact of RNA integrity and
blood sample storage conditions on the gene expression analysis. Results: Our
outcomes showed that the samples with RIN values more than 5.3 scarcely affected
the quantitative results of RNA-seq, and the influence of inherent cellular
physiological processes on RNA-seq output could be negligible. Conclusion: The
blood samples stored at 4 degrees C within 7 days with RIN values more than 5.3
were available for RNA-seq.
PMID- 29950863
TI - lncRNA H19 predicts poor prognosis in patients with melanoma and regulates cell
growth, invasion, migration and epithelial-mesenchymal transition in melanoma
cells.
AB - Introduction: Melanoma is a deadly malignancy and the poor prognosis of patients
with advanced disease is relatively poor. Recent studies indicate that long non
coding RNAs are involved in the pathogenesis of malignant melanoma. This study
aims to investigate the role of the long non-coding RNA H19 in melanoma and to
explore the underlying molecular mechanisms. Materials and methods: The
expression levels of H19 in clinical samples and melanoma cells were determined
by quantitative real-time PCR. The cell growth and cell metastasis were assessed
by Cell Counting Kit 8, cell invasion and wound healing assays. Cell apoptosis
and cell cycle were determined by flow cytometry. Protein levels were determined
by Western blotting assay. Results: H19 was highly expressed in melanoma tissues
compared to normal adjacent skin tissues, and the tissue expression level of H19
from melanoma patients with metastasis was significantly higher than that from
patients without distant metastasis. In addition, the high expression of H19 in
melanoma tissues was associated with advanced tumor invasion and TNM stage,
distal metastasis, lymph node metastasis and shorter overall survival in patients
with melanoma. The in vitro functional assays showed that knockdown of H19
inhibited cell growth, invasion and migration and also induced cell apoptosis as
well as G0/G1 arrest in melanoma cells. Further quantitative real-time PCR and
Western blot experiments showed that knockdown of H19 differentially regulated
the epithelial-mesenchymal transition (EMT)-related gene expressions and reversed
EMT in melanoma cell lines. Knockdown of H19 suppressed in vivo tumor growth and
modulated the expressions of EMT-related genes in nude mice. Conclusion: The
results from this study suggest that upregulation of H19 contributes to melanoma
development and progression.
PMID- 29950864
TI - Whole-body MRI versus 18F-FDG PET/CT for pretherapeutic assessment and staging of
lymphoma: a meta-analysis.
AB - Purpose: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed
tomography (PET/CT) is the reference standard in staging of 18F-FDG-avid
lymphomas; however, there is no recommended functional imaging modality for
indolent lymphomas. Therefore, we aimed to compare the performance of whole-body
magnetic resonance imaging (WB-MRI) with that of 18F-FDG PET/CT for lesion
detection and initial staging in patients with aggressive or indolent lymphoma.
Materials and methods: We searched the MEDLINE, EMBASE, and CENTRAL databases for
studies that compared WB-MRI with 18F-FDG PET/CT for lymphoma staging or lesion
detection. The methodological quality of the studies was assessed using version 2
of the "Quality Assessment of Diagnostic Accuracy Studies" tool. The pooled
staging accuracy (MU) of WB-MRI and 18F-FDG PET/CT for initial staging and for
assessing possible heterogeneity (chi2) across studies were calculated using
commercially available software. Results: Eight studies comprising 338 patients
were included. In terms of staging, the meta-analytic staging accuracies of WB
MRI and 18F-FDG PET/CT for Hodgkin lymphoma and aggressive non-Hodgkin lymphoma
(NHL) were 98% (95% CI, 94%-100%) and 98% (95% CI, 94%-100%), respectively. The
pooled staging accuracy of 18F-FDG PET/CT dropped to 87% (95% CI, 72%-97%) for
staging in patients with indolent lymphoma, whereas that of WB-MRI remained 96%
(95% CI, 91%-100%). Subgroup analysis indicated an even lower staging accuracy of
18F-FDG PET/CT for staging of less FDG-avid indolent NHLs (60%; 95% CI, 23%-92%),
in contrast to the superior performance of WB-MRI (98%; 95% CI, 88%-100%).
Conclusion: WB-MRI is a promising radiation-free imaging technique that may serve
as a viable alternative to 18F-FDG PET/CT for staging of 18FDG-avid lymphomas,
where 18F-FDG PET/CT remains the standard of care. Additionally, WB-MRI seems a
less histology-dependent functional imaging test than 18F-FDG PET/CT and may be
the imaging test of choice for staging of indolent NHLs with low 18F-FDG avidity.
PMID- 29950865
TI - A small compound spindlactone A sensitizes human endometrial cancer cells to
TRAIL-induced apoptosis via the inhibition of NAD(P)H dehydrogenase quinone 1.
AB - Introduction: Spindlactone A (SPL-A) is a novel small molecule inhibitor of TACC3
that selectively inhibits the nucleation of centrosome microtubules and induces
mitotic arrest in ovarian cancer cells. SPL-A is derived from dicoumarol which
inhibits the activity of NAD(P)H dehydrogenase quinone oxidoreductase 1 (NQO1).
This study aimed to investigate the mechanism by which SPL-A enhances TRAIL
induced apoptosis in endometrial carcinoma cells. Materials and methods:
Endometrial carcinoma cells were treated with SPL-A and/or TRAIL, and the
apoptosis and protein expression in the treated cells were examined. Results:
Combined treatment with SPL-A and TRAIL significantly induced apoptosis in
various human endometrial carcinoma cells, but not in normal human endometrial
stromal cells and endometrial epithelial cells. Notably, both NQO1 inhibitor
ES936 and NQO1 siRNA enhanced TRAIL-induced apoptosis of endometrial carcinoma
cells. Furthermore, SPL-A downregulated the expression of c-FLIP, Bcl-2, Bcl-xl,
and Mcl-1, while increasing p53 expression. Conclusion: In particular, luciferase
assay showed that SPL-A inhibited Bcl-2 promoter activity, and p53 inhibitor PFT
alpha could reverse the effect of SPL-A on Bcl-2 expression. Moreover, Bcl-2
overexpression inhibited the apoptosis induced by SPL-A and TRAIL. Taken
together, our results suggest that SPL-A sensitizes endometrial cancer cells to
TRAIL-induced apoptosis via the regulation of apoptosis-related proteins and the
inhibition of NQO1 activity.
PMID- 29950866
TI - MYO5A inhibition by miR-145 acts as a predictive marker of occult neck lymph node
metastasis in human laryngeal squamous cell carcinoma.
AB - Introduction: Each year, ~50,000 patients worldwide die of laryngeal squamous
cell carcinoma (LSCC) because of its highly metastatic properties. However, its
pathogenic mechanisms are still unclear, and in particular, the prediction of
metastasis remains elusive. This study aimed to define the role of microRNA-145
(miR-145) in LSCC progression. We also aimed to elucidate the clinical
significance of the miR-145/MYO5A pathway, especially the predictive function of
MYO5A in neck lymph node metastasis. Materials and methods: MYO5A and miR-145
expression was analyzed in 132 patients with LSCC, and associations between their
expression and clinicopathological features were evaluated. We validated the
regulatory relationship between miR-145b and MYO5A by dual luciferase reporter
assay. The role of the miR-145/MYO5A pathway in proliferation, metastasis, and
apoptosis was examined in vitro. The predictive functions of MYO5A in neck lymph
node metastasis and prognosis were defined according to patient follow-up.
Results: Our results showed downregulation of miR-145 in LSCC, which was
negatively correlated with MYO5A suppression of LSCC progression and metastasis.
MiR-145 directly regulated MYO5A expression in vitro and suppressed LSCC
proliferation and invasion while promoting apoptosis by inhibiting MYO5A.
Conclusion: Notably, overexpression of serum MYO5A in LSCC predicted cervical
nodal occult metastasis and poor prognosis, providing an effective indicator for
predicting neck lymph node metastasis and assessing LSCC prognosis.
PMID- 29950867
TI - TRIM44, a crucial target of miR-410, functions as a potential oncogene in
osteosarcoma.
AB - Purpose: Mounting evidence highlights the essential role of TRIM44 in tumor
initiation and malignant progression in several cancers; however, the function of
TRIM44 in osteosarcoma (OS) remains unknown. In this study, we aim to investigate
the role of TRIM44 and reveal its regulation by deregulated miRNAs in OS.
Materials and methods: The expression profiles of TRIM44 were examined by
immunohistochemistry, Western blotting, and qRT-PCR. The biological functions of
TRIM44 were investigated through siRNA-mediated knockdown experiments. The
regulation of TRIM44 by miR-410 was confirmed by Western blotting, dual
luciferase reporter assays, and rescue experiments. Results: TRIM44 was
upregulated in OS tissues and cell lines, and its overexpression was positively
correlated with TNM stage, metastasis, and recurrence. Knockdown of TRIM44 in OS
cells suppressed cell proliferation, migration, invasion, and epithelial
mesenchymal transition. In addition, we identified TRIM44 as a novel target gene
of miR-410 and miR-410 was remarkably downregulated in OS. Moreover,
overexpression of miR-410 suppressed proliferation, migration, invasion, and
epithelial-mesenchymal transition of OS cells by directly targeting TRIM44
expression. Furthermore, reintroduction of TRIM44 partially reversed miR-410
induced inhibitory effects on OS cells. Conclusion: Collectively, our findings
indicate that the miR-410/TRIM44 link is critical in the control of OS
progression.
PMID- 29950868
TI - lincROR influences the stemness and crizotinib resistance in EML-ALK+ non-small
cell lung cancer cells.
AB - Introduction: Echinoderm microtubule-associated protein-like 4-anaplastic
lymphoma kinase (EML4-ALK) is identified as an important pathogenic factor in
patients with non-small-cell lung cancer (NSCLC) and could induce a stem-like
phenotype in NSCLC cells. Crizotinib is commonly used for EML4-ALK+ NSCLC
treatment, but its acquired resistance results in tumor recurrence. Long
intergenic noncoding RNA, regulator of reprogramming (lincROR) is related to the
acquisition and maintenance of self-renewal and stemness features of cancer stem
cells. It has been documented that lincROR is implicated in chemoresistance.
However, the correlations of lincROR and EML4-ALK in stem cell-like properties
and of lincROR and crizotinib resistance in NSCLC cells are yet to be elucidated.
Patients and methods: In the present study, we investigated the expression
profile of lincROR in EML-ALK NSCLC tissues, and the potential role of lincROR in
prognosis was then analyzed. Subsequently, its association with stem cell-like
properties of EML-ALK+ NSCLC cells was determined. Furthermore, the correlation
of lincROR with crizotinib and the effects of lincROR and crizotinib on cell
viability of EML4-ALK+ NSCLC cells were all explored. Results: The results showed
that lincROR expression was upregulated in EML4-ALK+ NSCLC tissues relative to
EML4-ALK- NSCLC tissues. Low-expressed lincROR was related to a favorable
prognosis of patients with EML-ALK NSCLC. lincROR overexpression could enhance
the stemness features of EML-ALK+ NSCLC cells which were repressed by ALK
knockdown. Conclusion: We found that lincROR expression was significantly
inhibited because of the increased concentration of crizotinib in EML4-ALK+ NSCLC
cells. Furthermore, lincROR overexpression increased cell viability of EML4-ALK+
NSCLC cells, which was impaired by crizotinib. Conjointly, these results
suggested the important role of lincROR in EML-ALK+ NSCLC. lincROR may serve as a
potential therapeutic target to overcome chemotherapy resistance in EML-ALK+
NSCLC.
PMID- 29950869
TI - Omalizumab in allergic bronchopulmonary aspergillosis in patients with cystic
fibrosis.
AB - Background: Allergic bronchopulmonary aspergillosis (ABPA) is a condition
characterized by a Th2 response, serum eosinophilia, and increased total serum
IgE to Aspergillus fumigatus. ABPA occurs in cystic fibrosis (CF) and asthma.
Omalizumab is a humanized recombinant monoclonal antibody against IgE. Previous
studies reported borderline results when treating ABPA with omalizumab. Methods:
A retrospective study to investigate the efficacy of omalizumab in the treatment
of ABPA in CF patients was conducted at 3 CF centers in Israel and Belgium. Data
were obtained from the digital archive. We measured 4 outcome parameters: forced
expiratory volume in 1 second, body mass index, pulmonary exacerbations, and
steroid sparing. Results: The database was composed on the records of 9 patients.
None of the outcome parameters showed any improvement. A favorable outcome was
observed in patients with higher levels of posttreatment total IgE than those
with lower levels. CF-related diabetes and male gender showed trends for poorer
outcomes. Conclusion: No benefits were detected on treating ABPA in CF with
omlaizumb. Monitoring the total IgE was not helpful. A prospective randomized
double-blind study is needed.
PMID- 29950870
TI - Anaphylaxis: getting to the point (and price) of diagnosis and treatment.
PMID- 29950871
TI - Food allergy and anaphylaxis.
AB - Anaphylaxis is a severe and potentially life-threatening allergic reaction. There
are numerous potential causes, with food allergy being the leading cause in
children and the focus of this review. Most reactions involve an IgE-mediated
mechanism, although non-IgE-mediated and nonimmunologic reactions can occur.
Various cofactors to be discussed can place certain individuals at an increased
risk of severe or fatal anaphylaxis. The clinical manifestations of anaphylaxis
are broad and may involve multiple body systems. Diagnosis of food-related
anaphylaxis is primarily based on signs and symptoms and supported, wherever
possible, by identification and confirmation of a culprit food allergen. First
line treatment of anaphylaxis is intramuscular administration of epinephrine.
Long-term management is generally focused on strict allergen avoidance and more
recently on food desensitization using immunotherapy. This review provides an
overview of anaphylaxis with a specific focus on food allergy.
PMID- 29950873
TI - Underuse of epinephrine for the treatment of anaphylaxis: missed opportunities.
AB - Epinephrine is the only effective treatment for anaphylaxis but studies routinely
show underutilization. This is especially troubling given the fact that fatal
anaphylaxis has been associated with delayed administration of epinephrine. Many
potential barriers exist to the proper use of epinephrine during an anaphylactic
reaction. This article will explore both patient-and physician-related factors,
as well as misconceptions that all contribute to the underuse of epinephrine for
the treatment of anaphylaxis.
PMID- 29950874
TI - Economic considerations in the treatment of systemic allergic reactions.
AB - Epinephrine is a life-saving medication used to treat systemic allergic reactions
including anaphylaxis. Epinephrine autoinjectors (EAIs) are expensive and
worldwide availability is limited. Epinephrine prefilled syringes and epinephrine
kits are potentially lower-cost alternatives to EAIs. Advantages, disadvantages,
and costs of available products are discussed. The socioeconomic factors
impacting access to EAIs are described.
PMID- 29950875
TI - Cost-effectiveness analysis of treating transplant-eligible multiple myeloma
patients in Macedonia.
AB - Purpose: A decision-analytic model was developed to study the impact of induction
regimens vincristine, adriamycin, dexamethasone (VAD); thalidomide, dexamethasone
(TD); and bortezomib, dexamethasone (BorD), followed by autologous stem cell
transplantation (ASCT) for treating multiple myeloma (MM) patients in Macedonia.
Additionally, a cost-effectiveness analysis (CEA) of treatment sequences to
predict health effects and costs of different treatment sequences was performed.
Methods: Model strategies were based on a previously published study for treating
patients with MM in Macedonia. The data on disease progression and treatment
effectiveness were obtained from the published reports of randomized clinical
trials (GIMEMA M-B02005, IFM 2005-01). Utility parameters were extracted from the
literature. To compare treatment combinations, a decision tree model was
developed. Additionally, a cost analysis for one-time per-protocol costs was
performed from a Macedonian national health care perspective. The incremental
cost-effectiveness ratios (ICERs)/quality-adjusted life years (QALYs) gained for
1-, 10-, and 20-year time horizons were determined. Costs and health outcomes
were discounted to evaluate the effects of time in the model. Results: The one
time costs of BorD (EUR 5,656) were higher compared to VAD (EUR 303) and TD (EUR
329), increasing the overall costs for BorD. Thus, the BorD combination dominated
in the baseline results (1 and 10 years) and the ICER for TD vs. VAD was EUR
7,564/QALY (20 years, undiscounted model). However, in the discounted 20-year
model, BorD showed an ICER of EUR 138,747/QALY gained for BorD vs. TD.
Conclusion: The CEA performed indicated that considering 1-year time horizon
costs, VAD may be a cost-effective alternative vs. TD or BorD. However, for the
longer period (10 or 20 years) including the discounting of future costs and
outcomes, the TD and BorD combinations showed higher health benefits in terms of
QALYs and more cost-effective vs. VAD. These results should be considered as
supportive evidence by decision-makers and providers when deciding on the most
cost-effective induction treatment strategy prior to ASCT in MM patients.
PMID- 29950872
TI - Anaphylaxis in the 21st century: phenotypes, endotypes, and biomarkers.
AB - Anaphylaxis is the most serious of all allergic reactions and can be fatal. The
diagnosis is frequently delayed, and misdiagnosis often occurs with asthma or
urticaria. Biomarkers such as tryptase are not routinely checked, and appropriate
treatment with epinephrine is not administered in a majority of cases, increasing
the risk of poor outcomes. The objective of this review is to provide a better
understanding of the pathophysiology of anaphylaxis with a description of
phenotypes, endotypes, and biomarkers available in both the clinical and research
settings. Expanding knowledge with regard to the presentation, causes, and
triggers for anaphylaxis among health care providers will improve its diagnosis
and management, increase patient safety, and decrease morbidity and mortality.
PMID- 29950876
TI - Effect of aerobic exercise on echocardiographic epicardial adipose tissue
thickness in overweight individuals.
AB - Background: Epicardial adipose tissue thickness (EATT) measured by
echocardiography is a reliable indicator of visceral adipose tissue in the body
and metabolic syndrome. The objective of this work was to study the effect of 12
week aerobic exercise training on echocardiographic epicardial adipose tissue
thickness (EEATT), body composition and other metabolic parameters in
asymptomatic overweight adults. Methods: A total of 170 overweight and mild obese
individuals were randomly allocated to 12-week aerobic exercise program
(intervention group) or no supervised exercise (control group). The body fat
percentage and visceral fat levels were measured by bioelectric impedance
analyzer, and blood tests were conducted to measure lipids, fasting blood sugar
(FBS) and high-sensitivity C-reactive protein (Hs-CRP). The participants also
underwent transthoracic echocardiography to measure EATT. All the outcomes were
measured after 12 weeks. Repeated measures were analyzed using ANOVA and Mann
Whitney U-test were used to analyze the data. Results: EEATT values significantly
reduced by -16.24% (3.12+/-1.18 to 2.70+/-1.04, p<0.05) following 12 weeks of
aerobic exercise along with a reduction in weight by 2.96% (80.66+/-12.12 to
78.27+/-12.31, p<0.05), body mass index by 3.11% (29.20+/-2.71 to 28.29+/-2.81,
p<0.05) and waist circumference by 2.29% (94.82+/-7.23 to 92.64+/-7.33, p<0.05)
and improved Hs-CRP values. Conclusion: The 12-week aerobic exercise was found to
be effective in reducing EEATT in overweight and mild obese individuals. There
was significant improvement in body composition, blood lipids, FBS, Hs-CRP and
exercise capacity in intervention group compared to control group.
PMID- 29950877
TI - Predictors of major lower limb amputation in type 2 diabetic patients referred
for hospital care with diabetic foot syndrome.
AB - Purpose: This study was conducted to determine the risk factors of major lower
extremity amputations in type 2 diabetic patients referred for hospital care with
diabetic foot syndrome. Patients and methods: This retrospective study involved
225 type 2 diabetic patients referred for management of diabetic foot syndrome at
King Abdullah University Hospital in the period between January 2014 and December
2015. A structured customized diabetic foot data collection form with diabetic
foot characteristics chart was used for documentation of relevant information,
which checks for age, sex, body mass index, smoking, duration of diabetes,
diabetic control therapy, associated hypertension, cardiac diseases, stroke,
chronic renal impairment, renal replacement therapy (hem-dialysis), and history
of diabetes-related complication in both feet prior to the study period. The
predictors for major lower limb amputations were compared between groups using
chi-square test, and binary logistic regression was used to determine the factors
associated with major amputation. Results: Twenty-seven limbs underwent major
amputations with an overall rate of major amputation of 11.6%. The following
predictors were found to be associated with the higher incidence of major lower
limb amputations: duration of diabetes >=15 years, HbA1c >=8%, patients on
insulin, with hypertension, cardiac diseases, chronic renal impairment, stroke,
having gangrene, higher number of components, higher Wagner classification, and
ischemia. However, the rate did not differ significantly between men and women.
Conclusion: Presentation with gangrenous tissue and poor glycemic control are the
important risks and significant predictive factors for type 2 diabetes-related
major lower limb amputations.
PMID- 29950879
TI - Retrospective analysis of a lactose breath test in a gastrointestinal symptomatic
population of Northeast Italy: use of (H2+2CH4) versus H2 threshold.
AB - Background: Lactose malabsorption is normally evaluated by measuring exhaled H2
produced by intestinal flora, from unabsorbed lactose. However, differing
microbiome composition can lead to the production of CH4 instead of H2; hence,
some authors challenge the H2 method sensitivity and favor the evaluation of both
intestinal gases. Aim: To compare different approaches to usage of a lactose
breath test for lactose malabsorption diagnosis, after medical evaluation of
gastrointestinal symptoms. Methods: In a retrospective observational study, we
compared the 2 approaches in a population of 282 subjects in Northern Italy.
Following oral lactose administration, exhaled samples were harvested every 30
minutes for 4 hours and prepared for H2 and CH4 analysis. Basal gas levels were
subtracted from H2 and CH4 ppm and values at 4 hours and peaks were considered
for analysis. Results: Applying the standard methodology, which takes separately
into consideration H2 and CH4 produced in the intestinal lumen, the results
indicated that 11.7% of the patients were diagnosed "positive" for hypolactasia,
differently from what was expected. Conversely, taking into consideration the sum
of H2 and CH4, the percentage increased to 62.8%, closer to the expected one. No
significant differences were found when comparing the 2 groups for age, gender,
or symptoms. The sizable difference between the 2 approaches is likely linked to
gut microbiome variability, and consequently the different production of the 2
gases, in the population. Conclusion: The threshold normally used for lactose
breath test should be reconsidered and changed, merging H2 and CH4 stoichiometric
values to increase sensitivity.
PMID- 29950878
TI - Current perspectives on Mohs micrographic surgery for melanoma.
AB - Mohs micrographic surgery (MMS), a specialized surgical excision technique used
primarily in the treatment of skin cancers, is tissue sparing and provides
optimal margin control through evaluation of 100% of both the peripheral and deep
margin. The use of MMS for the treatment of malignant melanoma (MM) and melanoma
in situ (MIS) has been slow in gaining the same widespread acceptance that it has
for keratinocyte carcinomas despite its cost-effectiveness and the growing body
of evidence demonstrating similar or improved cure rates to standard wide local
excision. However, modern advances in immunohistochemical staining have continued
to greatly enhance the ability of Mohs surgeons to interpret MMS frozen sections
of melanoma specimens - the primary concern of most opponents of MMS for
melanoma. These advances, coupled with an increased recognition by professional
organizations of the utility of MMS in treating MM and MIS, have led to a rise in
the use of MMS for melanoma in recent years. Given the expanding role of MMS in
the treatment of cutaneous melanoma, this manuscript will describe how MMS is
performed, discuss the rationale and current evidence regarding the use of MMS
for MM and MIS, review the immunohistochemical stains currently available for use
in MMS, and consider special situations and future directions in this area of
growing interest.
PMID- 29950880
TI - The effect of hydroalcoholic extract of Teucrium polium L. on the inflammatory
markers and lipid profile in hypercholesterolemic rats.
AB - Background: Cardiovascular diseases are among the most common causes of mortality
worldwide. Therefore, it is necessary to control the risk factors of these
patients. Since the level of inflammatory markers and lipid profiles has
increased in cardiovascular diseases and due to the increasing role of plants in
the treatment of diseases, the current study aimed to investigate the effect of
hydroalcoholic extract of Teucrium polium on inflammatory markers and lipid
profile in hypercholesterolemic rats. Materials and methods: A total of 24 adult
male Wistar rats were randomly divided into four groups of six each and treated
with oral administration for 8 weeks. The control group received normal diet, the
sham group received high-cholesterol diet and experimental groups 1 and 2
received high-cholesterol diet in the 8 weeks and doses of 85 and 170 mg/kg,
respectively, of the T. polium hydroalcoholic extract (TPHAE) in the second 4
weeks. At the beginning and the end of the study, rats were examined for
biochemical parameters. The mean level of variables for each group was presented
as mean +/- standard error of mean. Results: The results of this study showed
that, after administration of TPHAE, there was a significant decrease in the mean
of inflammatory markers in all groups compared to sham group (P<0.001). Also,
administration of the extract significantly reduced the serum levels of
triglyceride, cholesterol and LDL-cholesterol and significantly increased the
serum HDL-cholesterol levels. In addition, the 170 mg/kg dose of TPHAE was the
most effective in reducing serum levels of inflammatory and lipid markers.
Conclusion: Treatment with TPHAE caused dose-dependent decrease in serum levels
of inflammatory markers and lipid profile in hypercholesterolemic rats.
Therefore, it can be applied as a natural product for the management of
cardiovascular diseases.
PMID- 29950882
TI - CYP3A and CYP2C19 activity in urine in relation to CYP3A4, CYP3A5, and CYP2C19
polymorphisms in Russian peptic ulcer patients taking omeprazole.
AB - Background: Proton pump inhibitors (PPIs) are metabolized by cytochrome P450.
CYP2C19 is the main isoenzyme for the majority of PPI, whereas CYP3A family is a
secondary enzyme for PPI biotransformation. Purpose: The aim of the study was to
find if CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17 genotypes are
connected with CYP3A and CYP2C19 activities in Russian peptic ulcer patients
taking omeprazole. Patients and methods: Forty-eight gastric or duodenal ulcer
patients (15 men, 33 women; mean age 55.0+/-15.3 years, age range 18-91 years)
from Moscow region of Russia were enrolled. Peripheral venous blood was collected
for DNA extraction, and real-time polymerase chain reaction was performed for
CYP3A5*3 A6986G (rs776746), CYP3A4*22 C>T in intron 6 (rs35599367),
CYP2C19*2G681A (rs4244285), CYP2C19*3G636A (rs4986893), and CYP2C19*17C-806T
(rs12248560) polymorphism analyses. Urine samples of patients were collected in
the morning between 6 and 9 am before food or drug intake. Urine cortisol and
6beta-hydroxycortisol concentrations (for CYP3A activity) and omeprazole and 5
hydroxyomeprazole concentrations (for CYP2C19 activity) were measured using high
performance liquid chromatography/mass spectroscopy. Results: We found a
connection between CYP2C19 genotypes and CYP3A activity. Median metabolic ratios
6beta-hydroxycortisol/cortisol (25%-75% percentiles) were 2.84 (1.99-4.39) for
CYP2C19 extensive metabolizers (EMs), 2.51 (1.86-4.73) for CYP2C19 ultra-rapid
metabolizers (UMs), and 1.45 (1.12-2.16) for CYP2C19 intermediate metabolizers
(IMs) + poor metabolizers (PMs). A statistically significant difference in CYP3A
activity (Mann-Whitney test) was found between CYP2C19 EMs vs CYP2C19 IMs+PMs
(p=0.006), between CYP2C19 UMs vs CYP2C19 IMs+PMs (p=0.018), and in multiple
comparison Kruskal-Wallis test (p=0.014). Conclusion: In CYP2C19 IMs+PMs, CYP3A
activity was significantly lower than in CYP2C19 EMs and UMs.
PMID- 29950883
TI - Venous thromboembolism risk assessments on trauma patients has suboptimal
interobserver reliability among inexperienced clinicians (fourth-year medical
students).
AB - Background: Venous thromboembolic disease is a major cause of morbidity and
mortality in hospitalized patients worldwide. The objective of this study is to
compare interobserver reliability for qualitative and quantitative venous
thromboembolism (VTE) risk assessments in hospitalized trauma patients. Methods:
We conducted a retrospective medical record review of 40 randomly selected trauma
patients admitted to a 448-bed urban level-I trauma center from January 2013 to
January 2014. Interclass correlation coefficient (ICC) was calculated based on a
two-way mixed model. The sample was equally distributed between patients admitted
to the floor and the intensive care unit (ICU). Eight fourth-year medical
students performed the risk assessments by the medical record. Two forms for risk
assessment were used: a qualitative screening and a quantitative screening. The
composite of intraobserver and interobserver variabilities was determined.
Results: The ICC for qualitative VTE risk assessments was 0.845 and for
quantitative VTE risk assessment was 0.628. Conclusion: To optimize accuracy of
VTE risk stratification and appropriate prophylaxis, medical students and first
year residents should be formally trained to perform quantitative assessments.
PMID- 29950884
TI - Stroke in-hospital survival and its predictors: the first results from Tabriz
Stroke Registry of Iran.
AB - Objective: The aim of this study was to determine the in-hospital survival of
patients referred to the 2 stroke centers in North-West of Iran during a full
seasonal year from April 2015. Methods: All the consecutive patients with stroke
admitted to the 2 main stroke centers at Tabriz (Imam Reza University Hospital
and Razi University Hospital) were recruited in this study. Stroke patients from
both ischemic and hemorrhagic subtypes were selected based on the registry data
and International Classification of Diseases, 10th edition. At admission, details
of examination including vital signs, neurologic and systemic examination,
Modified Rankin Scale, and Glasgow Coma Scale were recorded. Baseline
hematological and biochemical parameter assessments as well as computerized
tomographic scanning were conducted. Cox regression was used to investigate and
detect potential predictors of in-hospital survival. Results: A total of 1,990
patients with stroke were studied. Males comprised 52.1% (1,036) of the subjects.
The mean age of the patients was 65.8 years. Three hundred and fifty-seven
(17.9%) patients had hemorrhagic stroke vs 1,633 (82.1%) with ischemic stroke. In
hospital case-fatality proportion was 12.5% (95% CI: 11.1-14). Based on modified
Rankin Scale score at admission, 1,377 of 1,990 patients (69.2%) had a poor
outcome (modified Rankin Scale score >=3) at the admission time. The regression
analysis showed that at least 7 variables could independently predict hospital
survival of patients with stroke including age >=65 years, higher admission
modified Rankin Scale score, lower admission Glasgow Coma Scale score,
hemorrhagic stroke nature, diabetes, having valvular heart disease, and having
aspiration pneumonia. Conclusion: The case-fatality of stroke in the present
study setting is high and needs to be appropriately addressed through prevention
or management of some of these factors such as diabetes, pneumonia, and valvular
heart diseases.
PMID- 29950881
TI - The two faces of pannexins: new roles in inflammation and repair.
AB - Pannexins belong to a family of ATP-release channels expressed in almost all cell
types. An increasing body of literature on pannexins suggests that these channels
play dual and sometimes contradictory roles, contributing to normal cell
function, as well as to the pathological progression of disease. In this review,
we summarize our understanding of pannexin "protective" and "harmful" functions
in inflammation, regeneration and mechanical signaling. We also suggest a
possible basis for pannexin's dual roles, related to extracellular ATP and K+
levels and the activation of various types of P2 receptors that are associated
with pannexin. Finally, we speculate upon therapeutic strategies related to
pannexin using eyes, lacrimal glands, and peripheral nerves as examples of
interesting therapeutic targets.
PMID- 29950887
TI - Erratum: Analysis of opioid-mediated analgesia in Phase III studies of
methylnaltrexone for opioid-induced constipation in patients with chronic
noncancer pain [Corrigendum].
AB - [This corrects the article on p. 771 in vol. 8, PMID: 26586963.].
PMID- 29950886
TI - Curcumin alleviates pain and improves cognitive impairment in a rat model of
cobra venom-induced trigeminal neuralgia.
AB - Background: Cognitive impairment is a common complication in patients with
chronic neuropathic pain, without effective therapy. Recent works have indicated
that curcumin (Cur) possesses antinociceptive and neuroprotective potentials,
suggesting its possible effectiveness for the treatment of this complication.
Objective: The aim of this study was to explore the effects of Cur on pain
behaviors and cognitive impairment in rats with cobra venom-induced trigeminal
neuralgia (TN). Design: This is a randomized, controlled experiment. Setting:
This study was conducted at the Experimental Animal Center, Beijing Friendship
Hospital, Capital Medical University. Subjects: A total of 40 adult male Sprague
Dawley rats were used in this study. Methods: A cobra venom solution was injected
into the sheath of infraorbital nerve. Cur was administered intragastrically at
45 mg/kg twice daily for 28 successive days from postoperative day 15. Mechanical
allodynia was evaluated using von Frey filaments. Free behaviors were observed
using video recording. Cognitive capacity was tested using the Morris water maze.
Both morphology and ultrastructure of the CA1 hippocampal region were visualized
using hematoxylin and eosin (HE) staining and transmission electron microscopy,
respectively. Results: Cur treatment reduced mechanical allodynia and face
grooming activities but increased exploratory activities and improved spatial
learning and memory deficits. Microscopic examination revealed nucleus pyknosis,
swollen organelles, and decreased synapse density in the CA1 hippocampal region
after cobra venom injection. However, chronic Cur treatment reversed damage to
hippocampal neurons and synapses. Conclusion: Cur can alleviate pain, improve
spatial learning and memory deficits, and restore the damage to hippocampal
neurons and synapses in cobra venom-induced TN rats. Cur may be useful as an
adjuvant to treat chronic neuropathic pain-induced cognitive deficits.
PMID- 29950885
TI - Understanding short-term blood-pressure-variability phenotypes: from concept to
clinical practice.
AB - Clinic blood pressure (BP) is recognized as the gold standard for the screening,
diagnosis, and management of hypertension. However, optimal diagnosis and
successful management of hypertension cannot be achieved exclusively by a handful
of conventionally acquired BP readings. It is critical to estimate the magnitude
of BP variability by estimating and quantifying each individual patient's
specific BP variations. Short-term BP variability or exaggerated circadian BP
variations that occur within a day are associated with increased cardiovascular
events, mortality and target-organ damage. Popular concepts of BP variability,
including "white-coat hypertension" and "masked hypertension", are well
recognized in clinical practice. However, nocturnal hypertension, morning surge,
and morning hypertension are also important phenotypes of short-term BP
variability that warrant attention, especially in the primary-care setting. In
this review, we try to theorize and explain these phenotypes to ensure they are
better understood and recognized in day-to-day clinical practice.
PMID- 29950888
TI - Cryoneurolysis for the treatment of cervical facet joint syndrome: a technical
note.
AB - Objective: Neck pain has an annual prevalence of 30%. A frequent cause of neck
pain is cervical facet joint pain. In cases of refractory cervical facet joint
pain, radiofrequency can be employed, but the grade of evidence attested in
systematic reviews is fair. Cryoneurolysis has been reported to induce favorable
outcomes in lumbar facet joint pain. We sought to examine the feasibility of
cervical facet joint cryoneurolysis. Setting: Tertiary academic pain center.
Patients and methods: We report here the operative technique of cervical facet
joint cryoneurolysis for patients with cervical facet joint pain. The procedure
is performed under CT-guidance. The lesion points are defined with the help of
sensory stimulation. Results: Six cervical facet joint denervations were carried
out in five patients. All patients had an uneventful course with adequate pain
relief. Apart from soreness of the paravertebral muscles no severe side effects
were encountered. Conclusion: This is the first report of cryoneurolysis for the
treatment of cervical facet joint pain. The technique is feasible and warrants
further studies.
PMID- 29950889
TI - Chronic pain and geriatric syndromes in community-dwelling patients aged >=65
years.
AB - Background: In growing elderly populations, there is a heavy burden of
comorbidity and a high rate of geriatric syndromes (GS) including chronic pain.
Purpose: To assess the prevalence of chronic pain among individuals aged >=65
years in the Southern District of Israel and to evaluate associations between
chronic pain and other GS. Methods: A telephone interview was conducted on a
sample of older adults who live in the community. The interview included the
Brief Pain Inventory and a questionnaire on common geriatric problems. Results:
Of 419 elderly individuals who agreed to be interviewed 232 (55.2%) suffered from
chronic pain. Of those who reported chronic pain, 136 participants (68.6%) noted
that they had very severe or unbearable pain. There were statistically
significant associations between the pain itself and decline in patient's
functional status, increased falls, reduced mood, and cognitive decline.
Conclusion: The results of this study show that chronic pain is very common in
older adults and that it is associated with other GS. There is a need to increase
awareness of chronic pain in older adults and to emphasize the important role
that it plays in their care.
PMID- 29950890
TI - Short-term incubation of gabapentin or pregabalin does not affect chemically
induced injury in neuronal cell models in vitro.
AB - Purpose: Gabapentinoids are currently the mainstay of pharmacological treatments
for patients with neuropathic pain. Little is known about the effects of this
therapy on the integrity of neuronal networks, especially in patients with an
already-damaged nervous system. Since gabapentinoids can worsen cognitive
functions and recent studies have shown alterations in the brains of patients
with neuropathic pain, it may be possible that these drugs have neurotoxic
effects. Methods: Rat clonal PC12 pheochromocytoma (autonomic) and primary
sensory dorsal-root ganglion (DRG) neurons from newborn Wistar rats were employed
for this study. To mimic neuronal damage, cells were exposed to cytotoxins using
either hydrogen peroxide (H2O2) or vincristine. Results: No direct cytotoxic
effects were observed after incubating PC12 cells for 24 hours with increasing
concentrations of gabapentin or pregabalin using MTT cytotoxicity assays. Even a
7-day incubation did not cause cellular damage. Furthermore, in preinjured PC12
and DRG neurons, neither gabapentin nor pregabalin prevented or enhanced the
cytotoxic effects of H2O2 or vincristine after incubation for 24 hours and 7
days, respectively. Cell morphology and integrity of the cytoskeleton assessed by
employing immunostaining of cytoskeletal proteins (alpha-tubulin, neurofilament
L) remained intact and were not altered by gabapentinoids. Conclusion: Based on
these results, gabapentinoids are unlikely to be neurotoxic in cultured autonomic
(PC12) and sensory DRG cells, even when cells are preinjured. These results are
of high clinical relevance, as it seems unlikely that the morphological changes
recently observed in the brains of neuropathic pain patients are caused or
worsened by gabapentinoids.
PMID- 29950891
TI - Unexpectedly decreased plasma cytokines in patients with chronic back pain.
AB - Introduction: Chronic back pain is one of the most important socioeconomic
problems that affects the global population. Elevated levels of inflammatory
mediators, such as cytokines, have been correlated with pain, but their role in
chronic back pain remains unclear. The effectiveness of anti-inflammatory drugs
seems to be limited for chronic back pain. The authors wanted to investigate the
levels of inflammatory mediators in long-term medically treated patients with
persistent chronic back pain. Methods: Cytokine plasma levels of patients with
chronic back pain (n=23), compared to pain-free healthy controls (n=30), were
investigated by immunoassay. Patients with chronic back pain were exposed to long
term conservative medical therapy with physiotherapy and anti-inflammatories,
also combined with antidepressants and/or muscle-relaxants. Results: The patients
with chronic back pain expressed lower levels of the chemokines MCP1, CCL5, and
CXCL6 compared to pain-free healthy controls. Significantly lower concentrations
of the anti-inflammatory cytokines, interleukin (IL)-4 and granulocyte-colony
stimulating factor were also found. Interestingly, levels of proinflammatory
cytokines (IL-2, IL-6, IL-1beta, tumor necrosis factor alpha), IL-10, granulocyte
macrophage colony-stimulating factor, and stromal cell-derived factor 1 alpha
showed no significant differences between both groups. Conclusion: This decrease
of inflammatory mediators in medically treated patients with chronic back pain is
of unclear origin and might be either a long-term side effect of medical therapy
or related to chronic pain. Further longitudinal research is necessary to
elucidate the underlying cause of these findings.
PMID- 29950892
TI - Oxycodone ameliorates the inflammatory response induced by lipopolysaccharide in
primary microglia.
AB - Background: Activation of microglia participates in a wide range of
pathophysiological processes in the central nervous system. Some studies reported
that oxycodone (6-deoxy-7,8-dehydro-14-hydroxy-3-O-methyl-6oxomorphine) could
inhibit the overactivation of glial cells in rats' spinal cords. In the present
study, we observed the effect of oxycodone on inflammatory molecules and pathway
in lipopolysaccharide (LPS)-stimulated primary microglia in rats. Materials and
methods: Neonatal rats' primary microglia were exposed to various concentrations
(25, 50, 100 ng/mL) of oxycodone for 1 h after LPS stimulation for 24 h. The
levels of pro-inflammatory mediators, IL-1beta, TNF-alpha, and TGF-beta1/smad2/3
signaling pathway were measured. The activation situation of microglia and the
expression of TbetaR1 were observed by immunofluorescence. Results: Oxycodone at
25 ng/mL did not change the levels of proinflammatory molecules and TGF
beta1/smad2/3 signaling pathway in primary microglia, which was increased by LPS.
Oxycodone at 50 and 100 ng/mL could significantly suppress LPS-induced production
of TNF-alpha and IL-1beta and the expression of TNF-alphamRNA, IL-1betamRNA, and
TGF-beta1/smad2/3 signaling pathway. Conclusion: These findings indicate that
oxycodone, at relatively high clinically relevant concentration, can inhibit
inflammatory response in LPS-induced primary microglia. The detailed mechanism
needs to be investigated in future.
PMID- 29950893
TI - Evaluation of pulsed electromagnetic field therapy for the treatment of chronic
postoperative pain following lumbar surgery: a pilot, double-blind, randomized,
sham-controlled clinical trial.
AB - Background: The incidence of chronic postoperative pain following lumbar spinal
surgery has increased with the overall increase in the prevalence of lumbar
surgery. This study was conducted to evaluate the analgesic effectiveness of
pulsed electromagnetic field (PEMF) therapy in subjects with persistent pain
following lumbar surgery. Patients and methods: A randomized, double-blind, sham
controlled, multicenter study in 36 subjects with persistent low-back and/or
radiating leg pain after lumbar surgery was conducted. Eligible subjects were
randomized (1:1:1) to receive one of two doses of therapy (42-MUs or 38-MUs pulse
width) or treatment with a sham device. Subjects self-treated twice daily for 60
days. The primary end point was change in pain intensity (?PI) using the
Numerical Pain Rating Scale between average baseline (Days -5 to -1) and end of
treatment (Days 56-60) for lumbar and radiating leg pain. Secondary outcome
measures included the Oswestry Disability Index, Beck Depression Inventory-II,
Patient Global Impression of Change, and consumption of analgesics. Results: Low
back pain scores for the 42-MUs group decreased by 40.2% (p = 0.028), compared to
18.6% for the 38-MUs pulse width group (p = 0.037) and 25.6% for the sham group
(p = 0.013 per protocol population). Average leg pain scores decreased by 45.0%
(42 MUs, p = 0.009), 17.0% (38 MUs, p = 0.293), and 24.5% (sham, p = 0.065). The
proportion of subjects responding to therapy, time to 30% reduction in pain
scores, and Patient Global Impression of Change were improved with the PEMF 42
MUs device over the sham control, although results were associated with p-values
>0.05. Conclusion: PEMF therapy (42-MUs pulse width) was associated with trends
for a reduction in pain, compared to sham treatment. Secondary endpoints were
consistent with an overall beneficial effect of the PEMF 42-MUs pulse width
device.
PMID- 29950895
TI - Knowledge, attitude, and practice toward the daily management of PICC in
critically ill cancer patients discharged from intensive care units.
AB - Background: Peripherally inserted central catheters (PICCs) are widely used in
critically ill cancer patients. We aimed to investigate the status of knowledge,
attitude, and practice (KAP) toward the daily management of PICCs in critically
ill cancer patients discharged from intensive care units. Methods: Totally, 152
critically ill cancer patients discharged from two intensive care units in China
were surveyed using a self-administered KAP questionnaire. Patients' demographics
and PICC-related KAP scores were collected and analyzed using independent-samples
t-test and multivariate stepwise linear regression analysis. Results: All 152
patients completed the survey. The mean KAP scores were 32.61+/-3.80 points,
28.11+/-3.18 points, and 44.31+/-3.98 points, respectively. KAP scores were found
to have significant positive correlations with each other (P<0.05). The major
factors influencing the total KAP score were the PICC indwelling time and the
patient's educational degree, age, and place of residence (P<0.05). Conclusion:
We noted that KAP status toward the daily management of PICC in critically ill
cancer patients discharged from intensive care units is not optimistic and needs
to be further improved. Attention should be paid to the health education patterns
of KAP, and individualized instruction should be pursued.
PMID- 29950896
TI - INHBA upregulation correlates with poorer prognosis in patients with esophageal
squamous cell carcinoma.
AB - Purpose: INHBA, which encodes a member of the TGF-beta superfamily of proteins,
has been identified to play a critical role in different types of cancer.
However, its clinical significance in esophageal squamous cell carcinoma (ESCC)
has never been reported. Patients and methods: In this study, we collected 239
ESCC paraffin-embedded specimens and measured the expression of INHBA with
immunohistochemistry (IHC). The clinical and prognostic significance of INHBA
expression was statistically analyzed. What is more, we conducted a meta-analysis
to study the prognostic value of INHBA expression in multiple types of solid
tumors. Results: The results showed that INHBA expression was observed
predominantly in the cytoplasm of cells in the ESCC specimens. INHBA expression
was closely correlated with N categories (P=0.026). Kaplan-Meier analysis showed
that ESCC patients in the low INHBA expression subgroup had significantly better
prognosis than those with high INHBA level. Subgroup analysis revealed that INHBA
distinguished the disease-free survival (DFS) and overall survival (OS) when
patients were stratified by TNM stage status and N status. Multivariate analysis
results suggested that INHBA expression was an independent factor that affected
OS (HR =1.679, P=0.022) and DFS (HR =1.715, P=0.017). In the meta-analysis, six
papers with 1321 patients were included and patients with high INHBA level had
worse prognosis than patients with low INHBA level (HR 2.50, 95% CI 1.75-3.57,
P<0.0001). Conclusion: High INHBA level predicts poor prognosis in ESCC and other
solid tumors. More studies are required to elucidate the role of INHBA and its
clinical application in cancer settings.
PMID- 29950894
TI - Complexes formed by mutant p53 and their roles in breast cancer.
AB - Breast cancer is the most frequently diagnosed malignancy in women, and mutations
in the tumor suppressor p53 are commonly detected in the most aggressive
subtypes. The majority of TP53 gene alterations are missense substitutions,
leading to expression of mutant forms of the p53 protein that are frequently
detected at high levels in cancer cells. P53 mutants not only lose the
physiological tumor-suppressive activity of the wild-type p53 protein but also
acquire novel powerful oncogenic functions, referred to as gain of function, that
may actively confer a selective advantage during tumor progression. Some of the
best-characterized oncogenic activities of mutant p53 are mediated by its ability
to form aberrant protein complexes with other transcription factors or proteins
not directly related to gene transcription. The set of cellular proteins
available to interact with mutant p53 is dependent on cell type and extensively
affected by environmental signals, so the prognostic impact of p53 mutation is
complex. Specific functional interactions of mutant p53 can profoundly impact
homeostasis of breast cancer cells, reprogramming gene expression in response to
specific extracellular inputs or cell-intrinsic conditions. The list of protein
complexes involving mutant p53 in breast cancer is continuously growing, as is
the number of oncogenic phenotypes in which they could be involved. In
consideration of the functional impact of such complexes, key interactions of
mutant p53 may be exploited as potential targets for development of therapies
aimed at defusing the oncogenic potential of p53 mutation.
PMID- 29950897
TI - An increased number of negative lymph nodes is associated with a higher immune
response and longer survival in colon cancer patients.
AB - Background: The purpose of the present study was to examine the relationship
among the number of negative lymph nodes (LNs), the local and systemic immune
response, and survival in patients with colon cancer. Patients and methods: One
thousand one hundred and fifty-seven patients with colon cancer who underwent
surgery at Sun Yat-sen University Cancer Center between 2009 and 2014 were
included. We examined negative LNs in relation to the local and systemic immune
response, including percentage carcinoma, neutrophil and lymphocyte infiltration,
Crohn's-like reaction, neutrophil to lymphocyte ratio, platelets, and C-reactive
protein (CRP). Disease-free survival and overall survival were also examined. We
performed subgroup analysis based on the distribution of negative LNs. Results:
An increased number of negative LNs was associated with greater neutrophil
invasion (p=0.001), more lymphocyte invasion (p=0.001), and more Crohn's-like
reaction (p=0.001). No significant correlation was observed between negative LNs
and the neutrophil to lymphocyte ratio. More than 12 negative LNs were associated
with increased platelets and CRP levels. A higher number of negative LNs was
independently associated with longer disease-free survival in stage I+II patients
(p=0.004) and stage III patients (p=0.015), while negative LNs were also
independent prognostic factors in stage IV patients (p=0.007). Conclusion: Our
study suggests that negative LNs are indicators of the immune response and are
associated with a better prognosis in patients with colon cancer.
PMID- 29950899
TI - Role of key players in paradigm shifts of prostate cancer bone metastasis.
AB - The decreased bone mineral density and compromised bone strength predispose
individuals to skeletal osteoporosis. Both prostate cancer and bone metastasis
caused by cancer invasion have remained a great challenge to researchers. With
the advancement in the fields of biochemistry and biomechanics, the molecular
mechanisms that make prostate cancer metastasize to bone have recently been
identified, and they provide new molecular targets for drug development. Many
biochemical by-products have been identified to help in understanding the
interaction between the bone and the tumor. Enhanced clinical management of
patients with bone metastases was reported during the past decade; however, the
anticipated risk and the response to the therapy are still challenging to assess.
In this review, the key players that play a dominant role in secondary
osteoporosis are addressed. An attempt is made to provide the readers with a
clear understanding of the communication pathways between each of the cell types
involved in this vicious cycle. Furthermore, the role of Wnts, sclerostin, RANKL,
PTHrP, and their respective clinical studies are addressed in this study.
PMID- 29950898
TI - Optimal management of resected gastric cancer.
AB - Although advances in medical treatment for gastric cancer (GC) have been made,
surgery remains the mainstay of cure for patients with localized disease.
Improvement in surgical modalities leads to increased chance of cure for resected
patients, but a non-negligible number of patients eventually relapse. On this
basis, it has been hypothesized that the addition of complementary systemic or
local treatments (such as chemotherapy and radiotherapy) could help in improving
patients' survival by reducing the risk of recurrence. Several studies have tried
to identify the best approach in localized GC: some of them have assessed the
role of perioperative chemotherapy [CT] with different drug combinations, while
others have focused on the benefit obtained by addition of radiotherapy, whose
role is still under investigation. In particular, the role of chemoradiotherapy,
both in adjuvant and neoadjuvant settings, is still uncertain. In the last few
years, several clinicopathological and molecular factors have been investigated
and identified as potential prognostic markers in GC. Many of these factors could
have influenced the outcome of patients receiving combined treatments in the
abovementioned studies. Patients have not been generally distinguished by the
site of disease (esophageal, gastric and junctional cancers) and surgical
approach, making data difficult to be interpreted. The purpose of this review was
to shed light on these highly controversial topics.
PMID- 29950900
TI - Young patients with risk factors prevalent in the elderly - differences in
comorbidity depending on severity of psoriasis: a nationwide cross-sectional
study in Swedish health registers.
AB - Background: Association between psoriasis severity and cerebro- and
cardiovascular comorbidities has rarely been investigated. Aim: We aimed to
investigate differences in cerebro- and cardiovascular comorbidities by psoriasis
severity. Materials and methods: Using Swedish nationwide health-care registers,
new adult users of anti-psoriatic drugs (2007-2013) with a recorded diagnosis of
psoriasis/psoriatic arthritis or a filled prescription for calcipotriol were
included. Psoriasis severity was based on the type of anti-psoriatic treatment
(topical/mild, non-biologic systemic/moderate-to-severe, and biologics/ severe).
Age standardized prevalence rates of cerebro- and cardiovascular comorbidities
and their risk factors were compared between the groups. Results: We found that
severe psoriasis patients (N=2147) were younger than moderate-to-severe
(N=11,919) or mild (N=70,796) patients (median 44, 52, and 55 years). Prevalence
of hypertension was 29.9%, 32.6%, and 36.5%, myocardial infarction was 2.5%,
2.3%, and 1.8%, and stroke was 2.4%, 2.2%, and 1.1% in mild, moderate-to-severe,
and severe psoriasis patients, respectively. Diabetes prevalence was 7.6% in
mild, 8.0% in moderate-to-severe, and 10.7% in severe psoriasis. Conclusion:
Myocardial infarction and stroke were less common in patients with severe
psoriasis while, despite being younger, they had a higher prevalence of diabetes
and hypertension.
PMID- 29950901
TI - Global time trends in the incidence of esophageal squamous cell carcinoma.
AB - Background and aims: Esophageal squamous cell carcinoma (ESCC) is the dominant
histological type of esophageal cancer worldwide (90%). We aimed to provide an
update of the global temporal trends in the incidence of ESCC. Methods: Incidence
data for ESCC were collected from 30 well-established cancer registries from 20
countries in Europe, Northern America, Australia, or Asia for 1970-2015. Time
trends in annual age-standardized incidence rates of ESCC were assessed using
joinpoint analysis and log-linear regression. Age-period-cohort analysis was used
to estimate the influence of age, calendar-period, and birth-cohort on the
observed time trends in incidence. Results: The age-standardized incidence rates
of ESCC varied more than eightfold in men and sevenfold in women across
populations. In 2012, the highest rate of ESCC in men was observed in Nagasaki,
Japan (9.7/100,000 person-years) and in women in Scotland (2.7/100,000 person
years). In men, the incidence decreased globally during the study period, as well
as during the last few years. In women, the incidence increased in Japan (three
regions), the Netherlands, New Zealand, Norway, and Switzerland, whereas it
stabilized or decreased in other populations. Among ethnic groups in the United
States, black men and women had more pronounced decreases in incidence than other
groups. Generally, birth-cohort effects were stronger determinants of incidence
trends than calendar-period effects. Conclusion: In men, the global ESCC
incidence has decreased over time. In women, the incidence trends vary across
populations, and the rates have increased in some countries. Changes in the
prevalence of tobacco smoking and alcohol consumption may have contributed to
these time trends.
PMID- 29950902
TI - Parental age and risk of genetic syndromes predisposing to nervous system tumors:
nested case-control study.
AB - Purpose: Phacomatoses are genetic syndromes that are associated with increased
risk of developing nervous system tumors. Phacomatoses are usually inherited, but
many develop de novo, with unknown etiology. In this population-based study, we
investigated the effect of parental age on the risk of phacomatoses in offspring.
Patients and methods: The study was a population-based nested case-control study.
All individuals born and residing in Sweden between January 1960 and December
2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis
cases were identified and further classified as familial or nonfamilial. Ten
matched controls per case were randomly selected from the eligible population.
Data were analyzed using conditional logistic regression. Analyses were conducted
for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536).
Results: Compared with offspring of fathers aged 25-29 years, increased risk
estimates of nonfamilial neurofibromatosis were found for offspring of fathers
aged 35-39 years (odds ratio [OR]=1.43 [95% CI 1.16-1.74]) and >=40 years (OR
=1.74 [95% CI 1.38-2.19]). For other nonfamilial phacomatoses, the risk estimate
for offspring of fathers aged >=40 years was OR =1.23 (95% CI 1.01-1.50).
Paternal age was not associated with familial phacomatoses, and no consistent
association was observed with maternal age. Conclusion: The findings show a
consistent increase in risk of de novo occurrence of phacomatoses predisposing to
nervous system tumors in offspring with increasing paternal age, most pronounced
for neurofibromatosis, while maternal age did not seem to influence the risk.
These findings suggest an increasing rate of new mutations in the NF1 and NF2
genes in spermatozoa of older fathers.
PMID- 29950904
TI - Pregnancy-induced growth of a spinal hemangioblastoma: presumed mechanisms and
their implications for therapeutic approaches.
AB - Hemangioblastomas are benign tumors of the central nervous system (CNS) that may
occur either sporadically or as part of von Hippel-Lindau (VHL) disease, in which
they coexist with a series of other tumors outside the CNS. Because of their low
mitosis rate, hemangioblastomas usually have slow-growing and late
manifestations, but may cause sudden neurological symptoms if tumor hemorrhage
occurs. Few studies have evaluated the impact of pregnancy on the evolution of
hemangioblastomas. Some authors have reported tumor growth in women with VHL
disease, but no such association was observed by others. The influence of
pregnancy on sporadic hemangioblastomas remains largely unexplored. We report
here the case of a pregnant woman whose first manifestation of sporadic spinal
hemangioblastoma was life-threatening, rapidly progressive dysautonomia. In
addition, we discuss the role of pregnancy in the triggering of symptoms, as well
as the possibility of medically indicated delivery for the management of these
tumors.
PMID- 29950903
TI - Developing Class III malocclusions: challenges and solutions.
AB - Class III malocclusion represents a growth-related dentofacial deformity with
mandibular prognathism in relation to the maxilla and/or cranial base. Its
prevalence varies greatly among and within different races, ethnic groups, and
geographic regions studied. Class III malocclusion has a multifactorial etiology,
which is the expression of a moderate distortion of normal development as a
result of interaction between innate factors or genetic hereditary with
environmental factors. Various skeletal topographies of underlying Class III
malocclusion are due to discrepancy in the maxillary and mandibular growth along
with vertical and/or transverse problems apart from sagittal malformations. The
spectrum of complications for Class III malocclusion ranges in gravity from
dentoalveolar problems with functional anterior shift of the mandible to true
skeletal problems with serious maxillomandibular discrepancies, which makes its
diagnosis highly challenging in growing children. Concern regarding early
treatment and the need for interceptive care in the case of Class III
malocclusion has always been a dilemma, knowing that not all problems will be
solved in these cases until maxillomandibular growth is further completed, and
the long-term outcome of various treatment approaches may depend on the growth
tendency of an individual. Interceptive treatment of Class III malocclusions
should be undertaken if it prevents damage to the oral tissues and/or
significantly reduces the amount or severity of future orthodontic and surgical
interventions. This paper presents an overview of developing Class III
malocclusion, with the emphasis on challenges and their solutions based on the
best current available evidence.
PMID- 29950905
TI - Eight-ball hyphema after laser iridotomy in a patient with undiagnosed
hypocellular myelodysplastic syndrome.
AB - Introduction: We report a rare case of unexpected gross hyphema in the right eye
(OD) and eight-ball hyphema in the left eye (OS) from a bilateral laser iridotomy
in an acute primary angle-closure patient. We also demonstrated the effectiveness
of the inferior full-thickness trabeculectomy with daily intracameral air
injection as an alternative treatment in eight-ball hyphema. Case report: An 81
year-old Thai female presented with gross hyphema grade II OD and eight-ball
hyphema with blood-stained cornea OS after laser iridotomy. The patient was
scheduled for surgery and the preoperative blood test showed bicytopenia. We
performed anterior chamber washout OD and an inferior full-thickness
trabeculectomy with daily intracameral air injection OS. The hyphema completely
resolved on the following day OD and 3 days after surgery OS. The inferior bleb
OS did not raise with digital pressure and became nonfunctional in 7 days. No
recurrent hyphema was found in both eyes (OU) during 6 months of follow-up. This
patient was ultimately diagnosed with hypocellular myelodysplastic syndrome
(MDS). Conclusion: Gross hyphema after laser iridotomy can be seen in patients
with hypocellular MDS. The inferior full-thickness trabeculectomy is an
alternative surgical procedure for an eight-ball hyphema.
PMID- 29950906
TI - Atypical presentation of critical left main disease in an HIV-infected patient.
AB - Coronary artery disease is currently one of the leading causes of mortality in
patients with HIV. Severe left main disease (LMD) occurs in ~6% of the HIV
infected patients. We describe a case report of an atypical presentation of
silent critical LMD in an HIV-infected patient who underwent a low-risk exercise
stress test. The cardiovascular disease team should be vigilant for this latent
phenomenon, specifically within this subpopulation despite the high Duke
treadmill score.
PMID- 29950908
TI - Percutaneous direct current stimulation - a new electroceutical solution for
severe neurological pain and soft tissue injuries.
AB - There is a high medical need to improve the effectiveness of the treatment of
pain and traumatic soft tissue injuries. In this context, electrostimulating
devices have been used with only sporadic success. There is also much evidence of
endogenous electrical signals that play key roles in regulating the development
and regeneration of many tissues. Transepithelial potential gradients are one
source of the direct current (DC) electrical signals that stimulate and guide the
migration of inflammatory cells, epithelial cells, fibroblasts and mesenchymal
stem cells to achieve effective wound healing. Up to now, this
electrophysiological knowledge has not been adequately translated into a clinical
treatment. Here, we present a mobile, handheld electroceutical smart device based
on a microcontroller, an analog front end and a battery, which generates DC
electric fields (EFs), mimicking and modulating the patient's own physiological
electrical signals. The electrical stimulation is applied to percutaneous metal
probes, which are located close to the inflamed or injured tissue of the patient.
The treatment can be used in an ambulatory or stationary environment. It shows
unexpectedly, highly effective treatment for certain severe neurological pain
conditions, as well as traumatic soft tissue injuries (muscle/ligament ruptures,
joint sprains). Without EF intervention, these conditions, respectively, are
either virtually incurable or take several months to heal. We present three cases
- severe chronic cluster headache, acute massive muscle rupture of the rectus
femoris and an acute ankle sprain with a ruptured anterior talofibular ligament -
to demonstrate clinical effectiveness and discuss the fundamental differences
between mimicking DC simulation and conventional transcutaneous electric nerve
stimulation (TENS) or TENS-like implanted devices as used for peripheral nerve
cord, spinal cord or dorsal root stimulation.
PMID- 29950907
TI - Cannabinoids and agmatine as potential therapeutic alternatives for cisplatin
induced peripheral neuropathy.
AB - Cisplatin is a widely used antineoplastic agent in the treatment of various
cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has
the potential to result in limiting and/or reducing the dose, decreasing the
quality of life. Unfortunately, the mechanism for cisplatin-induced neuropathy
has not been completely elucidated. Currently, available treatments for
neuropathic pain (NP) are mostly symptomatic, insufficient and are often linked
with several detrimental side effects; thus, effective treatments are needed.
Cannabinoids and agmatine are endogenous modulators that are implicated in
painful states. This review explains the cisplatin-induced neuropathy and
antinociceptive effects of cannabinoids and agmatine in animal models of NP and
their putative therapeutic potential in cisplatin-induced neuropathy.
PMID- 29950910
TI - Larks, owls, swifts, and woodcocks among fruit flies: differential responses of
four heritable chronotypes to long and hot summer days.
AB - Purpose: Drosophila melanogaster and our own species share (Homo sapiens) the
history of relatively rapid out-of-Africa dispersal. In Eurasia, they had faced a
novel adaptive problem of adjustment of their circadian rhythmicity and night
sleep episode to seasonal variation in day length and air temperature. Both
species usually respond to heat and a short duration of night by reduction of the
amount of night sleep and prolongation of "siesta". To further explore
similarities between the two species in the ways of adjustment of their sleep
wake behavior to extreme environmental factors, this study examined the
possibility to distinguish four extreme chronotypes among fruit flies and the
possibility of the differential response of such chronotypes to light and heat
stressors. Materials and methods: Circadian rhythms of locomotor activity and
sleep-wake pattern were tested in constant darkness, and four strains of fruit
flies originating from three wild populations of Africa, Europe, and the USA were
selected to represent four distinct chronotypes: "larks" (early morning and
evening activity peaks), "owls" (late morning and evening peaks), "swifts" (early
morning and late evening peaks), and "woodcocks" (late morning and early evening
peaks). The circadian rhythms and sleep efficiency of the selected chronotypes
were further tested under such extreme conditions as either long day (LD20:4 at
20 degrees C) or a combination of LD20:4 with hot temperature (29 degrees C).
Results: Despite the identity of such experimental conditions for four
chronotypes, their circadian rhythms and sleep timing showed significantly
distinct patterns of response to exposure to heat and/or long days. All two-way
repeated measures analysis of variances yielded a significant interaction between
chronotype and time of the day (P<0.001). Conclusion: An experimental study of
heritable chronotypes in the fruit fly can facilitate a search for genetic
underpinnings of individual variation in vulnerability to circadian misalignment,
maladaptive sleep-wake behavior, and sleep disorders.
PMID- 29950909
TI - Biomarkers for primary biliary cholangitis: current perspectives.
AB - Primary biliary cholangitis (PBC) is a chronic progressive cholestatic disease
characterized by destruction of small- and medium-sized intrahepatic bile ducts.
It is no longer a rare disease, since many new asymptomatic cases are
incidentally identified. Liver biopsy is diagnostically critical but not always
feasible or practical to be performed. Many potential, noninvasive, markers have
been proposed to replace liver biopsy and further provide the assessment of
disease severity and ultimate prognosis. In this review, we evaluated serum
biomarkers proposed for diagnosis, extent of fibrosis, disease prognosis and
attempts for early prediction of treatment response. Older biochemical and
immunological markers are presented along with recent reports including the role
of microRNAs and promising results based on proteomics and metabolomics.
PMID- 29950911
TI - The Relational Aspects of Care Questionnaire: item reduction and scoring using
inpatient and accident and emergency data in England.
AB - Purpose: The Relational Aspects of Care Questionnaire (RAC-Q) is an electronic
instrument which has been developed to assess staff's interactions with patients
when delivering relational care to inpatients and those accessing accident and
emergency (A&E) services. The aim of this study was to reduce the number of
questionnaire items and explore scoring methods for "not applicable" response
options. Patients and methods: Participants (n=3928) were inpatients or A&E
attendees across six participating hospital trusts in England during 2015-2016.
The instrument, consisting of 20 questionnaire items, was administered by trained
hospital volunteers over a period of 10 months. Items were subjected to
exploratory factor analysis to confirm unidimensionality, and the number of items
was reduced using a range of a priori psychometric criteria. Two alternative
approaches to scoring were undertaken, one treated "not applicable" responses as
missing data, while the second adopted a problem score approach where "not
applicable" was considered "no problem with care." Results: Two short-form RAC-Qs
with alternative scoring options were identified. The first (the RAC-Q-12)
contained 12 items, while the second scoring option (the RAC-Q-14) contained 14
items. Scores from both short forms correlated highly with the full 20-item
parent form score (RAC-Q-12, r=0.93 and RAC-Q-14, f=0.92), displayed high
internal consistency (Cronbach's alpha: RAC-Q-12=0.92 and RAC-Q-14=0.89) and had
high levels of agreement (intraclass correlation coefficient [ICC]=0.97 for both
scales). Conclusion: The RAC-Q is designed to offer near-real-time feedback on
staff's interactions with patients when delivering relational care. The new short
form RAC-Qs and their respective method of scoring are reflective of scores
derived using the full 20-item parent form. The new short-form RAC-Qs may be
incorporated into inpatient surveys to enable the comparison of ward or hospital
performance. Using either the RAC-Q-12 or the RAC-Q-14 offers a method to reduce
missing data and response fatigue.
PMID- 29950912
TI - Introduction of a web portal for an Individual Health Management and
observational health data sciences.
AB - Background: There is a global trend to a stronger active involvement of persons
in the maintenance and restoring of health. The Competence Centre for
Complementary Medicine and Naturopathy (CoCoNat) of the Technical University of
Munich (TUM) has developed a lifestyle concept to enable each individual to
manage his or her health - Individual Health Management (IHM) - and a web-based
health portal named Virtual Tool for Education, Reporting, Information and
Outcomes (VITERIO(r)), which addresses these needs for practice and research.
Objectives: The objectives of this study were to establish a core set of
questionnaires for a self-assessment program on certain risk indications and
comprehensive protection factors of health and to develop and enhance 1) tools
for individual feedback, longitudinal self-monitoring, self-assessment, and (self
)care-planning; 2) training packages; 3) open notes and records for provider and
patient; and 4) tools for monitoring groups and single participants in various
indicators for individual coaching and scientific evaluation. Methods: The
CoCoNat of TUM, Faculty for Applied Health Science of Technische Hochschule
Deggendorf, VITERIO(r) company, IHM campus network, and Erich Rothenfubetaer
Foundation, Munich, provide a consortium responsible for content, research
strategy, technical production and implication, postgraduate education for IHM
coaches, implementation of IHM in various settings, and funding resources.
Results: A data set of indicators for health screening and self-monitoring of
findings, symptoms, health behavior, and attitudes are integrated into a web
based health portal named VITERIO(r). The article introduces some implemented
graphical solutions of developed tools and gives examples for daily use.
Conclusion: Behavioral change and adaptation in attitudes and personal values are
difficult issues of health education and lifestyle medicine. To address this
problem best, the implementation of a patient-centric, performance measures-based
program including open records and a blended learning concept were elaborated.
The combination of an individual web-based health portal with personal coaching
allows the implementation of IHM in everyday practice.
PMID- 29950913
TI - Comparison of statistical approaches for analyzing incomplete longitudinal
patient-reported outcome data in randomized controlled trials.
AB - Purpose: Missing data are a potential source of bias in the results of RCTs, but
are often unavoidable in clinical research, particularly in patient-reported
outcome measures (PROMs). Maximum likelihood (ML), multiple imputation (MI), and
inverse probability weighting (IPW) can be used to handle incomplete longitudinal
data. This paper compares their performance when analyzing PROMs, using a
simulation study based on an RCT data set. Methods: Realistic missing-at-random
data were simulated based on patterns observed during the follow-up of the knee
arthroscopy trial (ISRCTN45837371). Simulation scenarios covered different sample
sizes, with missing PROM data in 10%-60% of participants. Monotone and
nonmonotone missing data patterns were considered. Missing data were addressed by
using ML, MI, and IPW and analyzed via multilevel mixed-effects linear regression
models. Root mean square errors in the treatment effects were used as performance
parameters across 1,000 simulations. Results: Nonconvergence issues were observed
for IPW at small sample sizes. The performance of all three approaches worsened
with decreasing sample size and increasing proportions of missing data. MI and ML
performed similarly when the MI model was restricted to baseline variables, but
MI performed better when using postrandomization data in the imputation model and
also in nonmonotone versus monotone missing data scenarios. IPW performed worse
than ML and MI in all simulation scenarios. Conclusion: When additional
postrandomization information is available, MI can be beneficial over ML for
handling incomplete longitudinal PROM data. IPW is not recommended for handling
missing PROM data in the simulated scenarios.
PMID- 29950914
TI - Implementation of a patient blood management program in an Australian private
hospital orthopedic unit.
AB - Background: Preoperative anemia in surgical patients has been linked to increased
rates of allogeneic blood transfusion (ABT) and associated adverse patient
outcomes such as prolonged ventilation in intensive care, increased length of
hospital stay, and infections. We conducted a multifaceted implementation for
orthopedic surgeons to improve preoperative patient assessment of anemia and iron
deficiency to reduce perioperative blood transfusions. Materials and methods:
Using a before-and-after study design of independent samples, we recruited a
convenience sample of surgeons who performed primary total hip arthroplasty at 1
Australian private hospital. Our implementation intervention consisted of:
executive support, interactive education, and peer-to-peer support to encourage
adherence to the National Blood Authority's Patient Blood Management Program
(PBMP) guidelines. We also used monthly reminders, e-learning access, and
posters. Pre and post medical record audits evaluated preoperative blood tests,
preoperative anemia, and number of blood units transfused between day of surgery
until discharge. The primary outcome was an increase in the proportion of
patients with preoperative blood tests undertaken prior to total hip arthroplasty
surgery as recommended by the PBMP guidelines. Results: Audits from 239 pre- and
263 postimplementation patients from 3 surgeons were conducted. Our primary
outcome showed a significantly increased proportion of patients who had all the
required preoperative tests postimplementation (0% to 94.6%; P<0.0001).
Administration of ABT significantly decreased (pre: 9.2%, n=22; post: 2.3%, n=6;
P=0.001) as well as the standard 2 blood units transfused (pre: 73%, n=16; post:
17%, n=1; P=0.022). The time between preoperative tests and day of surgery
increased from 16 to 20 days (P<0.0001), allowing more time for physician's
review of test results. Conclusion: Our results demonstrated successful
implementation of a targeted PBMP to improve preoperative assessment to diagnose
and treat anemia and/or iron deficiency prior to orthopedic surgery. This avoided
unnecessary ABT and therefore mitigated potential risk to the patient.
PMID- 29950915
TI - Rhesus blood group haplotype frequencies among blood donors in southwestern
Uganda.
AB - Aim/objective: The study was undertaken to determine the Rhesus blood group
system and Rhesus haplotype frequencies among blood donors at Mbarara Regional
Blood Bank. Materials and methods: We included ethylene-diaminetetra-acetic acid
containing plasma samples and serum samples from recruited consented blood
donors. The Rh blood group system and the Rh haplotypes was established by the
incubation of appropriate antisera (anti-D, anti-E, anti-C, anti-e, and anti-c)
and cells at a temperature of 24 degrees C in microplates for 1 hour and the
reaction was read by gentle shaking and examining for agglutinations. Donors were
asked to fill in questionnaires, after we obtained the informed consent, to
assess their demographics. Results: Among the 386 participants, 233 were males
(60%) and 153 (40%) females. The Rh negative blood group percentage was 3.8%,
while the Rh haplotype frequencies were as follows: Dce dce 68.1%, dce dce 2.8%,
CD. dce 13%, cDE dce 12.4%, DC. DcE 1.6%, DcE DcE 1%, dC. dce 0.8%, and DcE DC.
0.3%. Conclusion: Given this frequency, a high prevalence of anti-D alloantibody
formation among those transfused is possible and could cause diverse effects,
especially in the Rh D positive women. We recommend additional research studies
on the role of autoimmunity to the transfused on the occurrence of Rh D variants
plus their implications on hemolytic disease of the fetus and newborn in Uganda.
This study recommends that the blood bank includes Rhesus haplotyping in its
protocols and that the finding be disseminated to donors and blood users.
PMID- 29950916
TI - Serum of sickle cell disease patients contains fetal hemoglobin silencing factors
secreted from leukocytes.
AB - Background: The mechanisms that regulate fetal hemoglobin (HbF) expression in
sickle cell disease (SCD) remain elusive. We previously showed that steady-state
SCD patients with high HbF levels due to a gamma-globin gene mutation demonstrate
strong inverse correlations between HbF levels and leukocyte counts, suggesting
that leukocytes play a role in regulating HbF in SCD. Materials and methods: To
further investigate the role of leukocytes in HbF expression in SCD, we examined
the presence of HbF silencing factors in the serum of 82 SCD patients who
received hydroxyurea (HU) therapy. Results: HU-mediated HbF induction was
associated with elevated total hemoglobin levels and improved red blood cell
parameters, but there was no correlation with reticulocyte or platelet counts.
Importantly, we again found that HU-induced HbF levels correlated with reductions
in both neutrophils and lymphocytes/monocytes, indicating that these cell
lineages may have a role in regulating HU-mediated HbF expression. Our in vitro
studies using CD34+-derived primary erythroblasts found that patient serum
preparations include HbF silencing factors that are distinct from granulocyte
macrophage colony-stimulating factor, and the activity of such factors decreases
upon HU therapy. Conclusion: Together, these results demonstrate the importance
of leukocyte numbers in the regulation of HbF levels for SCD patients both in
steady state and under HU therapy, and that leukocytes secrete HbF silencing
factors that negatively affect HbF expression in erythroid-lineage cells in SCD.
PMID- 29950917
TI - Evaluation of teachers training workshop at Kirkpatrick level 1 using retro-pre
questionnaire.
AB - Background: Teacher training focusing on teaching learning methodologies,
assessment tools, and approaches that motivate the teachers and enhance their
confidence is one of the fundamental programs of faculty development. The
objective of this study was to assess the self-reported perceived confidence of
faculty members after participating in a basic teachers training workshop.
Methodology: The retrospective post-then-pre design questionnaire was used for
evaluating the faculty members' self-reported perceived confidence at Kirkpatrick
level 1 (evaluation of reaction) after completing basic teachers training
workshops. The self-reported perceived confidence on 30 statements were analyzed
by 3 categories (not confident, confident, and highly confident) on a Likert
scale. Results: Out of 60 participants (18 in the 3rd and 21 each in the 4th and
5th teachers training workshops), 58 (96.67%) responded to all statements. The
mean age of the participants was 34.14+/-5.15 years; 70.7% were male and 29.3%
female. Overall, the self-reported perceived confidence level of the participants
of the 3rd (pre-training median 57, post-training median 70, p<0.001), 4th (pre
training median 51, post-training median 67, p<0.001) and 5th (pre-training
median 51, post-training median 68, p<0.001) training workshops was significantly
increased after training. There was a noticeable change in the level of
confidence of the participants after training. The observed percentage change in
self-reported perceived confidence was 29.63% in those who received no training
prior to joining college (n=51, 87.9%); this was 2 times more than those who
received some sort of training prior to teachers training (n=7, 12.1%).
Conclusion: Overall, the self-reported perceived confidence level of the
participants was significantly increased after teachers training workshop.
PMID- 29950918
TI - Time-variable medical education innovation in context.
AB - Background: Medical education is undergoing robust curricular reform with several
innovative models emerging. In this study, we examined current trends in 3-year
Doctor of Medicine (MD) education and place these programs in context. Methods: A
survey was conducted among Deans of U.S. allopathic medical schools using
structured phone interview regarding current availability of a 3-year MD pathway,
and/or other variations in curricular innovation, within their institution. Those
with 3-year programs answered additional questions. Results: Data from 107
institutions were obtained (75% survey response rate). The most common variation
in length of medical education today is the accelerated 3-year pathway. Since
2010, 9 medical schools have introduced parallel 3-year MD programs and another 4
are actively developing such programs. However, the total number of students in 3
year MD tracks remains small (n=199 students, or 0.2% total medical students).
Family medicine and general internal medicine are the most common residency
programs selected. Benefits of 3-year MD programs generally include reduction in
student debt, stability of guaranteed residency positions, and potential for
increasing physician numbers in rural/underserved areas. Drawbacks include
concern about fatigue/burnout, difficulty in providing guaranteed residency
positions, and additional expense in teaching 2 parallel curricula. Four
vignettes of alternative innovative and relevant curricular initiatives are also
presented in order to place 3-year MD programs in a broader context of medical
education reform in the U.S. Conclusion: Three-year MD pathways are the most
common accelerated alternative available at a small number of medical schools for
highly selected students. Long-term evaluation of these programs will be
essential to determine if these programs are meeting their goals (e.g.,
increasing the number of physicians in rural/underserved areas). Benefits and
shortcomings of such programs should be carefully examined when considering this
approach, or others described, as part of MD curricular options designed to
individualize medical education.
PMID- 29950919
TI - Broadening conceptions of medical student mistreatment during clinical teaching:
message from a study of "toxic" phenomenon during bedside teaching.
AB - Purpose: Part of the local hidden curriculum during clinical training of students
in the University of Maiduguri medical college in Nigeria, metaphorically
referred to as "toxic" practice by students, are situations where a teacher
belittles and/or humiliates a student who has fallen short of expected
performance, with the belief that such humiliation as part of feedback will lead
to improvement in future performance. Through a framework of sociocultural
perspective, this study gathered data to define the breadth and magnitude of this
practice and identify risk and protective factors with the aim of assessing
effectiveness of current intervention strategies. Materials and methods: Using a
mixed method research approach, quantitative data were collected from fourth-year
medical students in a Nigerian medical college through a survey questionnaire,
and qualitative data were obtained through a face-to-face, individual, semi
structured interview of students attending the same institution. Results:
Findings indicate that many students continue to experience "toxic" practice,
with only very few reporting the incidents to relevant authorities, raising
important questions about the appropriateness of current intervention efforts.
Conclusion: Current intervention strategies grossly underestimate the influence
of institutional forces that can lead to or promote this behavior. Acknowledgment
of this has implications for an appropriate intervention strategy.
PMID- 29950920
TI - Correction to: risk factors for cutaneous leishmaniasis in the rainforest of
Bolivia: a cross-sectional study.
AB - [This corrects the article DOI: 10.1186/s41182-018-0089-6.].
PMID- 29950921
TI - DNA nanostructure-directed assembly of metal nanoparticle superlattices.
AB - Structural DNA nanotechnology provides unique, well-controlled, versatile, and
highly addressable motifs and templates for assembling materials at the
nanoscale. These methods to build from the bottom-up using DNA as a construction
material are based on programmable and fully predictable Watson-Crick base
pairing. Researchers have adopted these techniques to an increasing extent for
creating numerous DNA nanostructures for a variety of uses ranging from
nanoelectronics to drug-delivery applications. Recently, an increasing effort has
been put into attaching nanoparticles (the size range of 1-20 nm) to the accurate
DNA motifs and into creating metallic nanostructures (typically 20-100 nm) using
designer DNA nanoshapes as molds or stencils. By combining nanoparticles with the
superior addressability of DNA-based scaffolds, it is possible to form well
ordered materials with intriguing and completely new optical, plasmonic,
electronic, and magnetic properties. This focused review discusses the DNA
structure-directed nanoparticle assemblies covering the wide range of different
one-, two-, and three-dimensional systems.
PMID- 29950922
TI - Nanoparticle transport pathways into tumors.
AB - Two transport pathways (interendothelial and transendothelial routes) have long
been proposed for entry of nanoparticles from the blood circulation into solid
tumors. We examine and discuss available evidence supporting interendothelial and
transendothelial transport processes and suggest new avenues for re-evaluating
these pathways. Understanding of integrative mechanisms controlling nanoparticle
extravasation into tumors is important for improving engineering and performance
of anti-cancer nanopharmaceuticals.
PMID- 29950923
TI - The Role of Macrophages in the Pathogenesis of ALI/ARDS.
AB - Despite development in the understanding of the pathogenesis of acute lung injury
(ALI)/acute respiratory distress syndrome (ARDS), the underlying mechanism still
needs to be elucidated. Apart from leukocytes and endothelial cells, macrophages
are also essential for the process of the inflammatory response in ALI/ARDS.
Notably, macrophages play a dual role of proinflammation and anti-inflammation
based on the microenvironment in different pathological stages. In the acute
phase of ALI/ARDS, resident alveolar macrophages, typically expressing the
alternatively activated phenotype (M2), shift into the classically activated
phenotype (M1) and release various potent proinflammatory mediators. In the later
phase, the M1 phenotype of activated resident and recruited macrophages shifts
back to the M2 phenotype for eliminating apoptotic cells and participating in
fibrosis. In this review, we summarize the main subsets of macrophages and the
associated signaling pathways in three different pathological phases of ALI/ARDS.
According to the current literature, regulating the function of macrophages and
monocytes might be a promising therapeutic strategy against ALI/ARDS.
PMID- 29950924
TI - Low-Copy Number Polymorphism in DEFA1/DEFA3 Is Associated with Susceptibility to
Hospital-Acquired Infections in Critically Ill Patients.
AB - DEFA1/DEFA3, genes encoding human neutrophil peptides (HNP) 1-3, display wide
ranging copy number variations (CNVs) and is functionally associated with innate
immunity and infections. To identify potential associations between DEFA1/DEFA3
CNV and hospital-acquired infections (HAIs), we enrolled 106 patients with HAIs
and 109 controls in the intensive care unit (ICU) and examined their DEFA1/DEFA3
CNVs. DEFA1/DEFA3 copy number ranged from 2 to 16 per diploid genome in all 215
critically ill patients, with a median of 7 copies. In HAIs, DEFA1/DEFA3 CNV
varied from 2 to 12 with a median of 6, which was significantly lower than that
in controls (2 to 16 with a median of 8, p = 0.017). Patients with lower
DEFA1/DEFA3 copy number (CNV < 7) were far more common in HAIs than in controls
(52.8% in HAIs versus 35.8% in controls; p = 0.014; OR, 2.010; 95% CI, 1.164
3.472). The area under the receiver operating characteristic (AUROC) of
DEFA1/DEFA3 CNV combined with clinical characteristics to predict the incidence
of HAIs was 0.763 (95% CI 0.700-0.827), showing strong predictive ability.
Therefore, lower DEFA1/DEFA3 copy number contributes to higher susceptibility to
HAIs in critically ill patients, and DEFA1/DEFA3 CNV is a significant hereditary
factor for predicting HAIs.
PMID- 29950925
TI - GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung
Injury through the TTF-1 Signaling Pathway.
AB - The reduction of pulmonary surfactant (PS) is essential for decreased pulmonary
compliance and edema in acute lung injury (ALI). Thyroid transcription factor-1
(TTF-1) plays a major role in the regulation of surfactant protein-A (SP-A), the
most abundant protein component of PS. Simultaneously, the glucagon-like peptide
1 (GLP-1) analogue can enhance SP-A expression in the lung. However, the
underlying mechanism is still unknown. The purpose of this study was to explore
whether liraglutide, a GLP-1 analogue, upregulates SP-A expression through the
TTF-1 signaling pathway in ALI. In vivo, a murine model of ALI was induced by
lipopolysaccharide (LPS). Pulmonary inflammation, edema, insulin level,
ultrastructural changes in type II alveolar epithelial (ATII) cells, and SP-A and
TTF-1 expression were analyzed. In vitro, rat ATII cells were obtained. SP-A and
TTF-1 expression in cells was measured. ShRNA-TTF-1 transfection was performed to
knock down TTF-1 expression. Our data showed that LPS-induced lung injury and
increase in insulin level, and LPS-induced reduction of SP-A and TTF-1 expression
in both the lung and cells, were significantly compromised by liraglutide.
Furthermore, we also found that these effects of liraglutide were markedly
blunted by shRNA-TTF-1. Taken together, our findings suggest that liraglutide
enhances SP-A expression in ATII cells and attenuates pulmonary inflammation in
LPS-induced ALI, most likely through the TTF-1 signaling pathway.
PMID- 29950927
TI - Understanding why child welfare clinic attendance and growth of children in the
nutrition surveillance programme is below target: lessons learnt from a mixed
methods study in Ghana.
AB - Background: Growth monitoring and promotion (GMP) programmes promote not only
child health but serve as a service delivery strategy to enhance coverage for
other crucial nutrition-specific interventions. This study compared community
based and facility-based GMP programme with respect to attendance rates,
children's nutritional status, caregivers' satisfaction with services received
and perceptions of service providers and users on factors influencing
utilization. Methods: Explanatory sequential mixed methods study conducted in Ga
West municipality, Ghana. It comprised 12-month secondary data analysis using
growth monitoring registers of 220 infants aged 0-3 months enrolled in two
community-based (CB = 104) and two facility-based (FB = 116) child welfare
clinics; cross-sectional survey (exit interview) of 232 caregiver-child pairs
accessing CB (n = 104) and FB services (n = 116); and in-depth interviews with 10
health workers and 15 mothers. Quantitative data were analyzed through Fisher's
exact, unpaired t-tests, and logistic regression at 95% confidence interval (CI)
using SPSS version 20. Qualitative data were analyzed by thematic content
analysis using ATLAS.ti 7.0. Results: Mean annual attendance to both programmes
was similar with an average of six visits per year. Only 13.6% of caregiver-child
pairs attained more than nine visits in the 12-months period. At least 60% of
children in both programs had improved weight-for-age z-scores (WAZ) scores
during participation. Predictors for improved WAZ were being underweight at
baseline (AOR:11.1, 95%CI:4.0-31.0), annual attendance of at least six visits
(AOR:2.2, 95%CI:1.1-4.1) and meeting the Ghana Health Service target of nine
visits (AOR:4.65, 95%CI:1.4-15.1). Compared to 31.5% CB users, significant
proportion of FB caregivers (57.4%) were visited at home. Half were dissatisfied
with services received (CB:55.6% vs. FB:62.0%, p = 0.437) citing long waiting
times, negative staff attitude and extortions of money. Regarding perceptions on
factors hindering service utilization, emerged themes included extremes of
maternal age, high parity, postpartum socio-cultural beliefs and practices,
financial commitments, undue delays, unprofessional staff behaviours, high
premium on vaccination and general misconceptions about the programme.
Conclusion: The association of increased attendance with improved growth
reaffirms the need to strengthen primary healthcare systems to improve service
delivery; sensitize caregivers on contribution of growth monitoring and promotion
to early child development; and increase contacts through home visits.
PMID- 29950926
TI - The Role of Galectins as Modulators of Metabolism and Inflammation.
AB - Galectins are beta-galcotosid-binding lectins. The function of galectins varies
with their tissue-specific and subcellular location, and their binding to
carbohydrates makes them key players in several intra- and extracellular
processes where they bind to glycosylated proteins and lipids. In humans, there
are 12 identified galectins, some with tissue-specific distribution. Galectins
are found inside cells and in the nucleus, cytosol, and organelles, as well as
extracellularly. Galectin-1, -2, -3, -4, -7, -8, -9, and -12 can all induce T
cell apoptosis and modulate inflammation. In the context of metabolic control and
loss of the same in, for example, diabetes, galectin-1, -2, -3, -9, and -12 are
especially interesting. This review presents information on galectins relevant to
the control of inflammation and metabolism and the potential to target galectins
for therapeutic purposes.
PMID- 29950928
TI - ETS1 is associated with cisplatin resistance through IKKalpha/NF-kappaB pathway
in cell line MDA-MB-231.
AB - Background: Platinum-based drugs are used extensively in neoadjuvant chemotherapy
for triple-negative breast cancer (TNBC), but their use can be limited by
resistance. In this study, we established cisplatin (DDP) resistant TNBC cells to
investigate the potential relationship among ETS1, IKKalpha/NF-kappaB and
resistance. Methods: The sensitivity was evaluated by MTT, apoptosis analysis.
The intracellular DDP concentration difference was tested by inductively coupled
plasma mass spectrometry (ICP-MS) method. Molecular pathological mechanism of DDP
resistance was explored by microarray analysis and PPI network analysis. The
ETS1, NF-kappaB signaling change were assessed by western blot and q-PCR in vitro
and vivo. The existing binds between ETS1 and the core IKKalpha promoter were
found by luciferase assay and chromatin immunoprecipitation technique (ChIP).
Results: MDA-MB-231/DDP (231/DDP) cell had a higher IC50 value of cisplatin,
lower intracellular DDP concentration, and lower apoptosis ratio than MDA-MB-231
(231/wt) cell line treated with DDP. Increased ABC transporters were induced by
the activation of NF-kappaB pathway in 231/DDP cells. ETS1, RPL6, RBBP8, BIRC2,
PIK3A and RARS were six important genes for DDP-resistance based on PPI network
and expression validation. Protein expression of ETS1 and IKKalpha were
significantly up-regulated in 231/DDP cells. However, inhibition of ETS1
expression enhances chemo-sensitivity to DDP and reversed the activation of NF
kappaB pathway in 231/DDP cells and subcutaneous transplantation tumor in vivo.
Moreover, there is existing binds between ETS1 and the core IKKalpha promoter
though luciferase assay and ChIP. Conclusion: This study enables us to understand
the functions of ETS1 in TNBC chemotherapy and suggests that ETS1 could be used
as a novel marker of poor response to DDP and a potential therapeutic target for
TNBC chemotherapy.
PMID- 29950929
TI - iTRAQ-Based Proteomic Analysis reveals possible target-related proteins and
signal networks in human osteoblasts overexpressing FGFR2.
AB - Background: Fibroblast growth factor receptor 2 (FGFR2) play a vital role in
skeletogenesis. However, the molecular mechanisms triggered by FGFR2 in
osteoblasts are still not fully understood. In this study, proteomics and
bioinformatics analysis were performed to investigate changes in the protein
profiles regulated by FGFR2, with the goal of characterizing the molecular
mechanisms of FGFR2 function in osteoblasts. Methods: In this study, FGFR2
overexpression cell line was established using the lentivirus-packaging vector in
human osteoblasts (hFOB1.19). Next, the isobaric tags for relative and absolute
quantitation (iTRAQ) in combination with the liquid chromatography-tandem mass
spectrometry (LC-MS/MS) method was used to compare the proteomic changes between
control and FGFR2-overexpression cells. Thresholds (fold-change of >= 1.5 and a P
value of < 0.05) were selected to determine differentially expressed proteins
(DEPs). The bioinformatics analysis including GO and pathway analysis were done
to identify the key pathways underlying the molecular mechanism. Results: A Total
of 149 DEPs was identified. The DEPs mainly located within organelles and
involved in protein binding and extracellular regulation of signal transduction.
ColI, TNC, FN1 and CDKN1A were strikingly downregulated while UBE2E3, ADNP2 and
HSP70 were significantly upregulated in FGFR2-overexpression cells. KEEG analysis
suggested the key pathways included cell death, PI3K-Akt signaling, focal
adhesion and cell cycle. Conclusions: To our knowledge, this is the first
protomic research to investigate alterations in protein levels and affected
pathways in FGFR2-overexpression osteoblasts. Thus, this study not only provides
a comprehensive dataset on overall protein changes regulated by FGFR2, but also
shed light on its potential molecular mechanism in human osteoblasts.
PMID- 29950930
TI - Deconstructing Hegemonic Masculinity: The Roles of Antifemininity, Subordination
to Women, and Sexual Dominance in Men's Perpetration of Sexual Aggression.
AB - The aim of this investigation was to examine a theoretically based mechanism by
which men's adherence to antifeminine norms is associated with their perpetration
of sexual aggression toward intimate partners. Participants were 208 heterosexual
men between the ages of 21-35 who had consumed alcohol in the past year. They
were recruited from a large southeastern United States city. Participants
completed self-report measures of hegemonic masculinity (i.e., antifemininity,
sexual dominance), masculine gender role stress, and sexual aggression toward an
intimate partner during the past 12 months. Results indicated that adherence to
the antifemininity norm and the tendency to experience stress when in subordinate
positions to women were indirectly related to sexual aggression perpetration via
adherence to the sexual dominance norm. Thus, the men who adhere strongly to
these particular hegemonic masculine norms may feel compelled to be sexually
aggressive and/or coercive toward an intimate partner in order to maintain their
need for dominance within their intimate relationship. Implications for future
research and sexual aggression prevention programming are discussed.
PMID- 29950931
TI - Self-Reported Daily Stress, Squelching of Anger and the Management of Daily
Stress and the Prevalence of Uterine Leiomyomata: The Ultrasound Screening Study.
AB - Self-reported daily stress, ways of managing stress and squelching anger were
examined in association with uterine leiomyomata (aka fibroids). These stress
factors were obtained from 560 Black and 375 White women enrolled in the National
Institute of Environmental Health Sciences Uterine Fibroid Study. Race-specific
prevalence differences (PD) and 95% confidence intervals (95% CI) were
calculated. Black women with severe stress had a prevalence of fibroids that was
11% higher (95% CI: 0%, 21%) than those in the no or mild stress group
(referent). White women with severe stress, compared to the referent, had a non
significantly (NS) higher prevalence of fibroids [PD = 7%; 95% CI: (-103, 213)].
For both groups, moderate daily stress was associated with a weak elevation (NS)
in fibroid prevalence. Black women who reported squelching their anger had an
elevated prevalence of fibroids (8%) compared to non-squelchers [95% CI: (-03,
153)] while there was no association for White women. Women with symptomatic
fibroids had higher stress than those without, but exclusion of symptomatic women
only slightly attenuated the associations. Consistent with a previous report,
symptomatic fibroids may cause stress. However, further research is warranted to
prospectively investigate a possible aetiologic role for stress in the
development of fibroids.
PMID- 29950932
TI - Measuring Depth in Still Water: Electrophysiologic Indicators of Residual
Consciousness in the Unresponsive Patient.
AB - Searching for evidence of consciousness in outwardly unresponsive patients
presents significant clinical challenges as the spectrum of disorders of
consciousness has become more clearly defined, with clinical examination,
functional MRI, and electrophysiologic tests having complementary roles in the
investigation of minimally conscious patients, those in a locked-in state, coma,
or in a vegetative state. Serial bedside electrophysiologic testing can probe for
higher order cortical responses temporally and spatially propagated through
cortical networks, while long-latency event-related potentials may help
differentiate patients with coma or vegetative state from a state of residual
consciousness. Transcranial magnetic stimulation co-registered to high-density
EEG may reveal widespread pulse-stimulated cortical activation of various brain
regions. These emerging electrophysiologic techniques show promise as powerful
diagnostic, prognostic, and therapeutic tools.
PMID- 29950933
TI - Gender Discrepancies in Academic Research: "If he can do it, why can't she?"
PMID- 29950934
TI - Who Will Develop Epilepsy Following Hospital Discharge? Think Again.
PMID- 29950935
TI - Fast Tapering of AEDs in the EMU: Worth the Risk or Risky Business?
PMID- 29950936
TI - Toward the "Fingerprint" of the Ictal Onset Zone - Is Mr. Morlet the Winner?
PMID- 29950937
TI - Links Between Epilepsy and ADHD: Time to Focus and Act.
PMID- 29950938
TI - Memory Enhancement: What's the Latest Buzz?
PMID- 29950939
TI - Real-Time Non-EEG Convulsive Seizure Detection Devices: They Work; Now What?
PMID- 29950940
TI - Epilepsy Surgical Resection Results in Better Seizure Control and Better Long
Term Health Related Quality Outcomes.
PMID- 29950941
TI - The Relation Between Lesion Removal and Seizure Freedom after Epilepsy Surgery:
All Lesions are Not Created Equal.
PMID- 29950943
TI - Molecular Mimicry may Underlie a Worm-Associated Epilepsy Syndrome.
PMID- 29950942
TI - Astrocytes: Stars of the Sacred Disease.
PMID- 29950944
TI - Finding Your Inner Light: Using Bioluminescence to Control Seizures.
PMID- 29950945
TI - Interneurons and the Ictal Orchestra.
PMID- 29950946
TI - Choking on Inhibition in the Reticular Thalamus.
PMID- 29950947
TI - Interference Resolved: Sorting out Picky Protocadherins in Epilepsy.
PMID- 29950948
TI - Serotonin in the Dorsal Raphe: As I Live and Breathe.
PMID- 29950949
TI - A Lunatic Dance: Circadian and Multidien Structures of Seizure Timing.
PMID- 29950950
TI - Delving Deeper into DEPDC5.
PMID- 29950951
TI - Major Organic Involvement in Women with Fabry Disease in Argentina.
AB - Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the
deficiency or absence of the alpha galactosidase A enzyme. Organic involvement in
men is well known, but in women it is controversial, partly due to the random X
chromosomes inactivation (Lyon hypothesis). The aim of this study was to describe
the organic involvement in women at the time of FD diagnosis. A descriptive,
cross-sectional and multicenter study was carried out. Thirty-five women with FD
from three reference centers in Argentina were evaluated. The mean age of the
whole group (n = 35) was 26.6 +/- 16.9 years; 22 were adult (over 18) and 13 were
paediatric patients. Enzymatic activity was performed in 29/35 patients, which
was normal in 24/29 (82.8%). Seven different mutations of the GLA gene were
found. The results showed urinary protein loss (45.7%) and decreased glomerular
filtration rate (31.4%), mainly in adults. And also, cornea verticillata (56.5%),
peripheral neuropathy (51.4%), cardiovascular manifestations (31.4%), hearing
loss (20%), angiokeratomas (20%), central nervous system (17.1%), and
gastrointestinal involvement (14.3%). Organic compromise in females with FD may
be as severe as in men. This analysis has demonstrated a significant proportion
of women with signs, symptoms, and major organic involvement at FD diagnosis.
PMID- 29950952
TI - Optimizing Sperm Collection Procedures in Zebrafish.
AB - Zebrafish are a highly-valued model organism used for developmental biology
research. Zebrafish can be used for genetic manipulation and hence, many mutant
and transgenic lines exist. It is impractical to maintain lines of adult
zebrafish, due to resource constraints and the need to continuously produce new
generations. Therefore, a practical way to preserve zebrafish lines is to freeze
sperm and retrieve lines using in vitro fertilization of fresh eggs. Most
existing in vitro protocols used by research labs have a wide variety of
fertilization rates (ranging from 0% to >90%). Due to this variability, lines may
be at risk of not being regenerated, and may be permanently lost. For this
project, aspects of existing published sperm collection protocols were tested and
modified, with the goal of improving the proportion of males giving quality
ejaculate. Males were tested for production of ejaculate by housing fish either
in groups or in separate, individual tanks the night before sperm collection. The
effect of age of male zebrafish and genetic background (5D and AB lines) on
production of quality ejaculate was also tested. Isolating males before sperm
collection significantly increased the proportion of individuals producing
quality ejaculate. The proportion of fish that gave quality ejaculate samples did
not co-vary with age between 17-68 weeks. Overall, AB fish were significantly
more likely to give quality ejaculate samples compared to 5D fish. Based on this
study, we strongly recommend separating male fish before sperm collection to
improve the likelihood of obtaining samples. Our results indicate that AB fish
give proportionately better samples than 5D fish, and this does not vary with age
between 17-68 weeks.
PMID- 29950953
TI - A SPECIAL MEETING REVIEW EDITION: Highlights in Hepatitis C Virus From the 2017
AASLD Liver Meeting: A Review of Selected Presentations From the 2017 AASLD Liver
Meeting * October 20-24, 2017 * Washington, DCSpecial Reporting on:* Efficacy,
Safety, and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic
Genotype 1-6 Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated
Analysis* Hepatitis C Virus Reinfection and Injecting Risk Behavior Following
Elbasvir/Grazoprevir Treatment in Participants on Opiate Agonist Therapy: Co-STAR
Part B* Efficacy and Safety of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in
Treatment-Naive Patients With Chronic HCV Genotype 3: An Integrated Phase 2/3
Analysis* SOF/VEL/VOX for 12 Weeks in NS5A-Inhibitor-Experienced HCV-Infected
Patients: Results of the Deferred Treatment Group in the Phase 3 POLARIS-1 Study*
Adherence to Pangenotypic Glecaprevir/Pibrentasvir Treatment and SVR12 in HCV
Infected Patients: An Integrated Analysis of the Phase 2/3 Clinical Trial
Program* The C-BREEZE 1 and 2 Studies: Efficacy and Safety of Ruzasvir Plus
Uprifosbuvir for 12 Weeks in Adults With Chronic Hepatitis C Virus Genotype 1, 2,
3, 4, or 6 Infection100% SVR With 8 Weeks of Ledipasvir/Sofosbuvir in HIV
Infected Men With Acute HCV Infection: Results From the SWIFT-C Trial (Sofosbuvir
Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1
Infected Individuals)PLUS Meeting Abstract SummariesWith Expert Commentary
by:Fred Poordad, MDChief, HepatologyUniversity Transplant CenterClinical
Professor of MedicineThe University of Texas Health, San AntonioSan Antonio,
Texas.
PMID- 29950954
TI - Positron Emission Tomography Imaging of Macrophages in Atherosclerosis with 18F
GE-180, a Radiotracer for Translocator Protein (TSPO).
AB - Intraplaque inflammation plays an important role in the progression of
atherosclerosis. The 18 kDa translocator protein (TSPO) expression is upregulated
in activated macrophages, representing a potential target to identify inflamed
atherosclerotic plaques. We preclinically evaluated 18F-GE-180, a novel third
generation TSPO radioligand, in a mouse model of atherosclerosis. Methods. Nine
hypercholesterolemic mice deficient in low density lipoprotein receptor and
apolipoprotein B48 (LDLR-/-ApoB100/100) and six healthy C57BL/6N mice were
injected with 10 MBq of 18F-GE-180. Specificity of binding was demonstrated in
three LDLR-/-ApoB100/100 mice by injection of nonradioactive reference compound
of 18F-GE-180 before 18F-GE-180. Dynamic 30-minute PET was performed followed by
contrast-enhanced CT, and the mice were sacrificed at 60 minutes after injection.
Tissue samples were obtained for ex vivo biodistribution measurements, and aortas
were cut into serial cryosections for digital autoradiography. The presence of
macrophages and TSPO was studied by immunohistochemistry. The 18F-GE-180
retention in plaque areas with different macrophage densities and lesion-free
vessel wall were compared. Results. The LDLR-/-ApoB100/100 mice showed large,
inflamed plaques in the aorta. Autoradiography revealed significantly higher 18F
GE-180 retention in macrophage-rich plaque areas than in noninflamed areas (count
densities 150 +/- 45 PSL/mm2 versus 51 +/- 12 PSL/mm2, p < 0.001). Prominent
retention in the vessel wall without plaque was also observed (220 +/- 41
PSL/mm2). Blocking with nonradioactive GE-180 diminished the difference in count
densities between macrophage-rich and noninflamed areas in atherosclerotic
plaques and lowered the count density in vessel wall without plaque. Conclusion.
18F-GE-180 shows specific uptake in macrophage-rich areas of atherosclerotic
plaques in mice. However, retention in atherosclerotic lesions does not exceed
that in lesion-free vessel wall. The third-generation TSPO radioligand 18F-GE-180
did not show improved characteristics for imaging atherosclerotic plaque
inflammation compared to previously studied TSPO-targeting tracers.
PMID- 29950955
TI - Awareness and Knowledge about Occupational Therapy in Jordan.
AB - Knowledge and awareness about occupational therapy (OT) are essential for the
delivery of quality care to all clients and for occupational therapists' (OTRs)
job satisfaction. OT has been a poorly understood profession in Jordan. The
current study reports on the assessment of Jordanians' awareness and knowledge of
occupational therapy. Convenience sampling was used. There were 829 participants
(474 males, 355 females), with mean age of 32 +/- 11.6 yrs. They were recruited
from the three main geographical areas of Jordan (northern, central, and
southern) and from all educational levels. The sample included 222 (26.8%)
healthcare personnel, 146 (17.6%) clients, and 461 (55.6%) lay persons.
Participants completed questionnaires, and the results revealed that 48% of the
sample had poor or no knowledge about OT, while 28.3% were unaware of it. Also,
OT was commonly (50%) perceived to be exclusively targeting people with
disabilities (PWDs) and neurological and physical conditions (58% and 53%, resp.)
in addition to exclusively providing services for the rehabilitation of the upper
extremity (48%). Common misconceptions associated with OT were that OTRs
prescribe medication (43%) and OTRs are physiotherapists (44%). These preliminary
findings suggest that efforts need to be directed by OTRs, the Jordanian Society
of Occupational Therapy (JSOT), and the Ministry of Health to preserve the OT
identity and value and promote knowledge about OT in the public and among members
of interdisciplinary teams. More interprofessional learning needs to be
incorporated within the curricula and placements of all healthcare personnels.
PMID- 29950956
TI - Plasma glutamine and glutamic acid are potential biomarkers for predicting
diabetic retinopathy.
AB - Introduction: Diabetic patients with a long disease duration usually accompanied
complication such as diabetic retinopathy, but in some patients had no
complication. Objectives: We analyzed differences in plasma metabolites according
to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D)
patients with disease duration >= 15 years. Methods: A cohort of 183 T2D patients
was established. Their biospecimens and clinical information were collected in
accordance with the guidelines of the National Biobank of Korea, and the Korean
Diabetes Association. DR phenotypes of the subjects were verified by
ophthalmologic specialists. Plasma metabolites were analyzed using gas
chromatography time-of-flight mass spectrometry and ultra-performance liquid
chromatography-quadrupole time-of-flight mass spectrometry. And these results
were analyzed using multivariate statistics. Results: For metabolomic study,
propensity score matched case and control subjects were chosen. Mean age of the
subjects was 66.4 years and mean T2D duration was 22.2 years. Metabolomic
identification revealed various carbohydrates, amino acids, and organic compounds
that distinguished between age- and sex-matched non-diabetic controls and T2D
subjects. Among these, glutamine and glutamic acid were suggested as the most
distinctive metabolites for the presence of DR. Receiver operating
characteristics curves showed an excellent diagnostic value of combined (AUC =
0.739) and the ratio (AUC = 0.742) of glutamine and glutamic acid for DR. And
these results were consistent in validation analyses. Conclusion: Our results
imply that plasma glutamine, glutamic acid, and their ratio may be valuable as
novel biomarkers for anticipating DR in T2D subjects.
PMID- 29950957
TI - Perioperative and Survival Outcomes Following Neoadjuvant FOLFIRINOX versus
Gemcitabine Abraxane in Patients with Pancreatic Adenocarcinoma.
AB - Context: Neoadjuvant chemotherapy is increasingly used in borderline resectable
and locally advanced pancreatic cancer to facilitate surgical resection.
Objective: To compare progression free survival and overall survival in patients
receiving neoadjuvant FOLFIRINOX with those receiving gemcitabine/abraxane.
Design: Retrospective cohort study. Setting: University of Colorado Hospital from
2012-2016. Participants: Patients with pancreatic adenocarcinoma. Interventions:
Neoadjuvant FOLFIRINOX or gemcitabine/abraxane. Outcome Measures: Perioperative
outcomes, progression free survival, and overall survival were compared between
groups. A multivariate Cox proportional hazard model was applied to evaluate
survival outcomes. Results: We identified 120 patients: 83 (69.2%) FOLFIRINOX and
37 (30.8%) gemcitabine/abraxane. The FOLIFRINOX group was younger and had a lower
ECOG performance status (p<0.05). Patients in the FOLFIRINOX group were more
likely to undergo surgical resection compared to gemcitabine/abraxane (66.3% vs.
32.4%, p=0.002). Among all patients, median follow up was 16.9 months and
FOLFIRINOX was associated with improved PFS (15.3 vs. 8.2 months, p=0.006), but
not overall survival (23.5 vs. 18.7 months, p=0.228). In these patients, insulin
dependent diabetes was associated with a worse progression free survival and
overall survival and surgical resection was protective. Among surgically resected
patients, median follow up was 21.1 months and there was no difference in
progression free survival (19.5 vs. 15.1 months) or overall survival (27.4 vs.
19.8 months) between the FOLFIRINOX and gemcitabine/abraxane groups, respectively
(p>0.05). Insulin-dependent diabetes and a poor-to-moderate pathologic response
was associated with worse progression free survival and overall survival.
Conclusion: Neoadjuvant FOLFIRINOX may improve progression free survival by
increasing the proportion of patients undergoing surgical resection. Improved
understanding of the role for selection bias and longer follow up are needed to
better define the impact of neoadjuvant FOLFIRINOX on overall survival.
PMID- 29950958
TI - Lipid Peroxidation, Advanced Glycation end Products and Antioxidant Status in
Patients on Dialysis.
AB - Oxidative stress increases the risk of cardiovascular disease in patients on
chronic dialysis. In this study, we examined markers of oxidative stress and
antioxidant status in haemodialysis (HD) patients in order to find out their
relationship to the dialysis treatment. Study included 25 patients on long-term
haemodialysis (HD) and 30 control subjects. Levels of malonyldialdehyde+4
hydroxyalkenes (MDA+4-HNE), advanced glycation end products (AGEs) and superoxide
dismutase (Cu/ZnSOD) were assayed in plasma or serum. Mean plasma level of MDA+4
HNE was 2-fold higher and AGEs 4-fold higher in HD patients, comparing to control
subjects. Also Cu/ZnSOD were significantly elevated in dialysis patients.
Positive correlation between AGEs as well as Cu/ZnSOD concentration and duration
of HD treatment (r=0,68, p<0,007; r=0,53, p<0,006) was found. Significantly
increased oxidative stress may accelerate atherosclerotic changes and
cardiovascular complications in haemodialysis patients but seems to be, at least
in part, counteracted by enhanced antioxidant capacity.
PMID- 29950959
TI - Topiramate Treatment May Interfere With Urinary Cortisol Measurement By
Radioimmunoassay (RIA) - A Case Report.
PMID- 29950960
TI - Immunotherapy of Breast Cancer.
PMID- 29950961
TI - TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First
Results on the Influence of Tumor-Infiltrating Lymphocytes.
AB - Background: Despite advancements in the treatment of primary and metastatic
breast cancer, many patients lack a durable response to these treatments.
Patients with triple-negative breast cancer (TNBC) and human epidermal growth
factor receptor 2(HER2)-positive breast cancer who do not have a pathological
complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor
prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a
predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer.
These patient populations could also be suitable for novel treatment strategies
including neoepitope-based therapies. This work analyses the effect of TILs on
the pCR in neoadjuvantly treated patients in the TILGen study and presents the
procedures aimed at establishing neoepitope-based therapies in this study.
Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for
the presented analysis concerning the association between TILs and pCR. A total
of 146 patients could be identified within the TILGen study. TILs were evaluated
as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The
phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR
by logistic regression adjusted for estrogen receptor status, progesterone
receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was
seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while
the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio
was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a
strong predictor of pCR in TNBC and HER2-positive breast cancer patients.
Implications for the use of this information including the effect on prognosis
might help to identify patients most likely to benefit from a neoepitope-based
therapy approach.
PMID- 29950962
TI - The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer.
AB - While detailed analysis of aberrant cancer cell signaling pathways and changes in
cancer cell DNA has dominated the field of breast cancer biology for years, there
now exists increasing evidence that the tumor microenvironment (TME) including
tumor-infiltrating immune cells support the growth and development of breast
cancer and further facilitate invasion and metastasis formation as well as
sensitivity to drug therapy. Furthermore, breast cancer cells have developed
different strategies to escape surveillance from the adaptive and innate immune
system. These include loss of expression of immunostimulatory molecules, gain of
expression of immunoinhibitory molecules such as PD-L1 and HLA-G, and altered
expression of components involved in apoptosis. Furthermore, the composition of
the TME plays a key role in breast cancer development and treatment response. In
this review we will focus on i) the different immune evasion mechanisms used by
breast cancer cells, ii) the role of immune cell infiltration in this disease,
and (iii) implication for breast cancer-based immunotherapies.
PMID- 29950963
TI - Immunooncology in Breast Cancer: Active and Passive Vaccination Strategies.
AB - Immunotherapies are set to become part of the therapeutic repertoire for breast
cancer in the near future. Active vaccination is a promising strategy, especially
in tumors that have a specific tumor-associated antigen. Although cellular
immunotherapies have not yet shown efficacy, new technologies are on the way to
improve this approach. Given the recent Food and Drug Administration approval of
chimeric antigen receptor (CAR) T cells for leukemia, it is only a question of
time before solid tumors will follow. However, not all breast cancer patients
will respond to cellular or other immunotherapy. Hence, we must define
subpopulations of breast cancer patients who benefit from this new approach.
PMID- 29950964
TI - Checkpoint Inhibitors in Breast Cancer - Current Status and Future Directions.
AB - Antineoplastic agents directly targeting tumor cells have represented the major
strategy of systemic anticancer therapy for many years. Nevertheless, overcoming
resistance mechanisms remains a great challenge because treatment options are
limited in many cases. From this point of view, immunotherapeutic approaches seem
promising in a broad spectrum of solid tumors. These include in particular the
currently available inhibitors directed against immune checkpoints leading to a
significant T-cell activation. To date, the programmed death receptor 1 (PD-1)
and its ligand are the most prominent targets in this context. However, the role
of checkpoint inhibitors in the treatment of breast cancer is still being
debated, and the main focus is on triple-negative breast cancer patients as a
target population in many ongoing trials. Moreover, the potential superiority of
combinations with other anticancer drugs such as cytotoxics and targeted agents
will be discussed.
PMID- 29950965
TI - Differentiation between Pure Mucinous Breast Carcinomas and Fibroadenomas with
Strong High-Signal Intensity on T2-Weighted Images from Dynamic Contrast-Enhanced
Magnetic Resonance Imaging.
AB - Objective: This study aimed to identify characteristics that can differentiate
between pure mucinous breast carcinomas (PMBCs) and fibroadenomas (FAs) with
strong high-signal intensity on T2-weighted images (T2-SHi) from dynamic contrast
enhanced magnetic resonance imaging (DCE-MRI). Methods: The DCE-MRI tumor
characteristics were compared and analyzed between 35 PMBCs and 70 FAs with T2
SHi. Results: Multivariate analysis revealed that delayed enhancement pattern was
the only significant independent predictor (p = 0.007). Conclusion: A delayed
enhancement pattern is the most reliable characteristic for differentiating PMBCs
from FAs with T2-SHi from DCE-MRI.
PMID- 29950966
TI - Why Do Women with Breast Cancer Get Diagnosed and Treated Late in Sub-Saharan
Africa? Perspectives from Women and Patients in Bamako, Mali.
AB - Background: Breast cancer, the most common cancer among women worldwide, has a
high mortality rate in low-income countries. In sub-Saharan Africa, most breast
cancer patients are diagnosed with advanced disease. Some studies have quantified
the time delay to diagnosis in sub-Saharan Africa, but very few have used
qualitative methods to understand barriers leading to delay. This study analyses
barriers throughout a breast cancer patient's pathway from symptom recognition to
treatment in Mali. Method: Three focus group discussions were conducted. The
model of pathways to treatment was used to structure the results into 4 time
intervals: appraisal, help-seeking, diagnosis, and treatment, with a focus on
barriers during each interval. Results: The main barriers during the appraisal
interval were a low level of breast cancer knowledge among women, their families,
and medical professionals, and during the help-seeking interval, mistrust in the
community health care centers and economic hardship. Barriers during the
diagnosis interval were low quality of health care services and lack of social
support, and during the pretreatment interval high costs and lack of specialized
services. Conclusion: Multilevel interventions are needed to ensure access,
availability, and affordability of a minimum standard of care for breast cancer
patients in sub-Saharan Africa.
PMID- 29950967
TI - Dystrophic Calcifications in the Breast from Secondary Hyperparathyroidism.
AB - Background: Soft tissue calcification is common in patients with secondary
hyperparathyroidism who have received long-term treatment with hemodialysis.
However, calcifications in the breast parenchyma are not common. We report a case
of a woman with dystrophic breast calcifications from secondary
hyperparathyroidism. Case Report: A 65-year-old woman presented with a palpable
mass in her right breast which she had discovered 1 month ago. She had a medical
history of end-stage renal disease. Mammography and ultrasound revealed large
dystrophic calcifications in both breasts. Core needle biopsy was performed for
calcifications in the right breast, and the pathologic diagnosis was dystrophic
calcification in the stroma from secondary hyperparathyroidism. Conclusion:
Reviewing our case will contribute to a fast and correct diagnosis in patients
with dystrophic breast calcifications and lab results indicating secondary
hyperparathyroidism, and will help discriminate these benign lesions from
malignancies.
PMID- 29950968
TI - ABC4 Consensus: Assessment by a German Group of Experts.
AB - The Advanced Breast Cancer Fourth Consensus (ABC4) on diagnosis and treatment of
advanced breast cancer (ABC) again took place in Lisbon, on November 2-4, 2017,
and was chaired by Fatima Cardoso, MD, PhD. This year's contents focused very
much on new developments in the treatment of ABC. For example, the significance
of inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) in hormone receptor
(HR)-positive ABC, of dual antibody blockade in human epidermal growth factor
receptor 2 (HER2)-positive ABC, and of poly(ADP-ribose) polymerase (PARP)
inhibition in triple-negative ABC, as well as the potential therapeutic
consequences, were discussed. Other key issues were BRCA-associated breast
cancer, treatment of brain metastases, and personalized therapy decision-making
using molecular testing (so-called 'precision medicine'). As in past years, an
important objective of the ABC conference was cooperation with representatives of
patient organizations from around the world. This cooperation was further
intensified during the ABC4. Following the main conference, the 'Global Alliance'
was founded, with the goal of publicizing and coordinating measures necessary
worldwide from the patient advocates' standpoint. - The ABC consensus inevitably
cannot accommodate country-specific needs, due to the truly global expert panel.
Therefore, a working group of German breast cancer experts commented - as in the
past years - on the on-site voting results by the ABC panelists upon which the
final ABC4 consensus will be based, with particular consideration of the German
guidelines on diagnosis and treatment of breast cancer for everyday treatment in
Germany.
PMID- 29950969
TI - Modulatory Effects of a Novel Cyclized Peptide in Reducing the Expression of
Markers Linked to Alzheimer's Disease.
AB - Despite many studies attempt to identify the primary mechanisms underlying
neurodegeneration in Alzheimer's disease (AD), the key events still remain
elusive. We have previously shown that a peptide cleaved from the
acetylcholinesterase (AChE) C-terminus (T14) can play a pivotal role as a
signaling molecule in neurodegeneration, via its interaction with the alpha7
nicotinic acetylcholine receptor. The main goal of this study is to determine
whether a cyclized variant (NBP14) of the toxic AChE-derived peptide can
antagonize the effects of its linear counterpart, T14, in modulating well-known
markers linked to neurodegeneration. We investigate this hypothesis applying
NBP14 on ex-vivo rat brain slices containing the basal forebrain. Western blot
analysis revealed an inhibitory action of NBP14 on naturally occurring T14
peptide, as well as on endogenous amyloid beta, whereas the expression of the
nicotinic receptor and phosphorylated Tau was relatively unaffected. These
results further confirm the neurotoxic properties of the AChE-peptide and show
for the first time in an ex-vivo preparation the possible neuroprotective
activity of NBP14, over a protracted period of hours, indicating that T14 pathway
may offer a new prospect for therapeutic intervention in AD pathobiology.
PMID- 29950971
TI - A Strategy to Reduce Bias of Entropy Estimates in Resting-State fMRI Signals.
AB - Complexity analysis of resting-state blood oxygen level-dependent (BOLD) signals
using entropy methods has attracted considerable attention. However,
investigation on the bias of entropy estimates in resting-state functional
magnetic resonance imaging (fMRI) signals and a general strategy for selecting
entropy parameters is lacking. In this paper, we present a minimizing error
approach to reduce the bias of sample entropy (SampEn) and multiscale entropy
(MSE) in resting-state fMRI data. The strategy explored a range of parameters
that minimized the relative error of SampEn of BOLD signals in cerebrospinal
fluids where minimal physiologic information was present, and applied these
parameters to calculate SampEn of BOLD signals in gray matter regions. We
examined the effect of various parameters on the results of SampEn and MSE
analyses of a large normal aging adult cohort (354 healthy subjects aged 21-89
years). The results showed that a tradeoff between pattern length m and tolerance
factor r was necessary to maintain the accuracy of SampEn estimates. Furthermore,
an increased relative error of SampEn was associated with an increased
coefficient of variation in voxel-wise statistics. Overall, the parameters m = 1
and r = 0.20-0.45 provided reliable MSE estimates in short resting-state fMRI
signals. For a single-scale SampEn analysis, a wide range of parameters was
available with data lengths of at least 97 time points. This study provides a
minimization error strategy for future studies on the non-linear analysis of
resting-state fMRI signals to account for the bias of entropy estimates.
PMID- 29950970
TI - Alzheimer's Disease and Type 2 Diabetes: A Critical Assessment of the Shared
Pathological Traits.
AB - Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM) are two of the most
prevalent diseases in the elderly population worldwide. A growing body of
epidemiological studies suggest that people with T2DM are at a higher risk of
developing AD. Likewise, AD brains are less capable of glucose uptake from the
surroundings resembling a condition of brain insulin resistance. Pathologically
AD is characterized by extracellular plaques of Abeta and intracellular
neurofibrillary tangles of hyperphosphorylated tau. T2DM, on the other hand is a
metabolic disorder characterized by hyperglycemia and insulin resistance. In this
review we have discussed how Insulin resistance in T2DM directly exacerbates
Abeta and tau pathologies and elucidated the pathophysiological traits of
synaptic dysfunction, inflammation, and autophagic impairments that are common to
both diseases and indirectly impact Abeta and tau functions in the neurons.
Elucidation of the underlying pathways that connect these two diseases will be
immensely valuable for designing novel drug targets for Alzheimer's disease.
PMID- 29950973
TI - Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve
Injury Induced Apoptosis via Yes Associated Protein.
AB - Background: Low-intensity pulsed ultrasound (LIPUS) has been used in clinical
studies. But little is known about its effects on the central nervous system
(CNS), or its mechanism of action. Retinal ganglion cells (RGCs) are CNS neuronal
cells that can be utilized as a classic model system to evaluate outcomes of
LIPUS protection from external trauma-induced retinal injury. In this study, we
aim to: (1) determine the pulse energy and the capability of LIPUS in RGC
viability, (2) ascertain the protective role of LIPUS in optic nerve (ON) crush
induced retinal injury, and 3) explore the cellular mechanisms of RGC apoptosis
prevention by LIPUS. Methods: An ON crush model was set up to induce RGC death.
LIPUS was used to treat mice eyes daily, and the retina samples were dissected
for immunostaining and Western blot. The expression of yes-associated protein
(YAP) and apoptosis-related proteins was detected by immunostaining and Western
blot in vitro and in vivo. Apoptosis of RGCs was evaluated by TUNEL staining, the
survival of RGCs and retained axons were labeled by Fluoro-gold and Tuj1
antibody, respectively. Rotenone was used to set up an in vitro cellular
degenerative model and siYAP was used to interfering the expression of YAP to
detect the LIPUS protective function. Results: LIPUS protected RGC from loss and
apoptosis in vivo and in vitro. The ratio of cleaved/pro-caspase3 also decreased
significantly under LIPUS treatment. As a cellular mechanical sensor, YAP
expression increased and YAP translocated to nucleus in LIPUS stimulation group,
however, phospho-YAP was found to be decreased. When YAP was inhibited, the LIPUS
could not protect RGC from caspase3-dependent apoptosis. Conclusion: LIPUS
prevented RGCs from apoptosis in an ON crush model and in vitro cellular
degenerative model, which indicates a potential treatment for further traumatic
ON injury. The mechanism of protection is dependent on YAP activation and
correlated with caspase-3 signaling.
PMID- 29950972
TI - Different Expression Levels of Human Mutant Ubiquitin B+1 (UBB+1) Can Modify
Chronological Lifespan or Stress Resistance of Saccharomyces cerevisiae.
AB - The ubiquitin-proteasome system (UPS) is the main pathway responsible for the
degradation of misfolded proteins, and its dysregulation has been implicated in
several neurodegenerative diseases, including Alzheimer's disease (AD). UBB+1, a
mutant variant of ubiquitin B, was found to accumulate in neurons of AD patients
and it has been linked to UPS dysfunction and neuronal death. Using the yeast
Saccharomyces cerevisiae as a model system, we constitutively expressed UBB+1 to
evaluate its effects on proteasome function and cell death, particularly under
conditions of chronological aging. We showed that the expression of UBB+1 caused
inhibition of the three proteasomal proteolytic activities (caspase-like (beta1),
trypsin-like (beta2) and chymotrypsin-like (beta5) activities) in yeast.
Interestingly, this inhibition did not alter cell viability of growing cells.
Moreover, we showed that cells expressing UBB+1 at lower level displayed an
increased capacity to degrade induced misfolded proteins. When we evaluated cells
during chronological aging, UBB+1 expression at lower level, prevented cells to
accumulate reactive oxygen species (ROS) and avert apoptosis, dramatically
increasing yeast life span. Since proteasome inhibition by UBB+1 has previously
been shown to induce chaperone expression and thus protect against stress, we
evaluated our UBB+1 model under heat shock and oxidative stress. Higher
expression of UBB+1 caused thermotolerance in yeast due to induction of
chaperones, which occurred to a lesser extent at lower expression level of UBB+1
(where we observed the phenotype of extended life span). Altering UPS capacity by
differential expression of UBB+1 protects cells against several stresses during
chronological aging. This system can be valuable to study the effects of UBB+1 on
misfolded proteins involved in neurodegeneration and aging.
PMID- 29950975
TI - Corrigendum: Cell Mechanotransduction With Piconewton Forces Applied by Optical
Tweezers.
AB - [This corrects the article on p. 130 in vol. 12, PMID: 29867363.].
PMID- 29950974
TI - Elevated Pressure Increases Ca2+ Influx Through AMPA Receptors in Select
Populations of Retinal Ganglion Cells.
AB - The predominate type of AMPA receptor expressed in the CNS is impermeable to Ca2+
(CI-AMPAR). However, some AMPA receptors are permeable to Ca2+ (CP-AMPAR) and
play important roles in development, plasticity and disease. In the retina,
ganglion cells (RGCs) are targets of disease including glaucoma and diabetic
retinopathy, but there are many types of RGCs and not all types are targeted
equally. In the present study, we sought to determine if there are differences in
expression of AMPARs amongst RGC subtypes, and if these differences might
contribute to differential vulnerability in a model of stress. Using cultured
RGCs we first show that acute exposure to elevated pressure increased expression
of Ca2+-permeable AMPA receptors (CP-AMPARs) in some, but not all classes of
RGCs. When RGCs were sampled without regard to subtype, AMPA currents, measured
using patch clamp recording, were blocked by the CP-AMPAR blocker PhTX-74 to a
greater extent in pressure-treated RGCs vs. control. Furthermore, imaging
experiments revealed an increase in Ca2+ influx during AMPA application in
pressure-treated RGCs. However, examination of specific RGC subtypes using
reporter lines revealed striking differences in both baseline AMPAR composition
and modulation of this baseline composition by stress. Notably, ON alpha RGCs
identified using the Opn4 mouse line and immunohistochemistry, had low expression
of CP-AMPARs. Conversely, an ON-OFF direction selective RGC and putative OFF
alpha RGC each expressed high levels of CP-AMPARs. These differences between RGC
subtypes were also observed in RGCs from whole retina. Elevated pressure further
lowered expression of CP-AMPARs in ON alpha RGCs, but raised expression in ON-OFF
and OFF RGCs. Changes in CP-AMPAR expression following challenge with elevated
pressure were correlated with RGC survival: ON alpha RGCs were unaffected by
application of pressure, while the number of putative OFF alpha RGCs declined by
approximately 50% following challenge with pressure. Differences in expression of
CP-AMPARs between RGC subtypes may form the underpinnings for subtype-specific
synaptic plasticity. Furthermore, the differential responses of these RGC
subtypes to elevated pressure may contribute to the reported resistance of ON
alpha, and susceptibility of OFF and ON-OFF RGCs to injury in models of glaucoma.
PMID- 29950976
TI - Corrigendum: A Population of Projection Neurons that Inhibits the Lateral Horn
but Excites the Antennal Lobe through Chemical Synapses in Drosophila.
AB - [This corrects the article on p. 30 in vol. 11, PMID: 28515683.].
PMID- 29950977
TI - Genes and Aggressive Behavior: Epigenetic Mechanisms Underlying Individual
Susceptibility to Aversive Environments.
AB - Over the last two decades, the study of the relationship between nature and
nurture in shaping human behavior has encountered a renewed interest. Behavioral
genetics showed that distinct polymorphisms of genes that code for proteins that
control neurotransmitter metabolic and synaptic function are associated with
individual vulnerability to aversive experiences, such as stressful and traumatic
life events, and may result in an increased risk of developing psychopathologies
associated with violence. On the other hand, recent studies indicate that
experiencing aversive events modulates gene expression by introducing stable
changes to DNA without modifying its sequence, a mechanism known as
"epigenetics". For example, experiencing adversities during periods of maximal
sensitivity to the environment, such as prenatal life, infancy and early
adolescence, may introduce lasting epigenetic marks in genes that affect
maturational processes in brain, thus favoring the emergence of dysfunctional
behaviors, including exaggerate aggression in adulthood. The present review
discusses data from recent research, both in humans and animals, concerning the
epigenetic regulation of four genes belonging to the neuroendocrine, serotonergic
and oxytocinergic pathways-Nuclear receptor subfamily 3-group C-member 1 (NR3C1),
oxytocin receptor (OXTR), solute carrier-family 6 member 4 (SLC6A4) and monoamine
oxidase A (MAOA)-and their role in modulating vulnerability to proactive and
reactive aggressive behavior. Behavioral genetics and epigenetics are shedding a
new light on the fine interaction between genes and environment, by providing a
novel tool to understand the molecular events that underlie aggression. Overall,
the findings from these studies carry important implications not only for
neuroscience, but also for social sciences, including ethics, philosophy and law.
PMID- 29950978
TI - Cooperative and Competitive Contextual Effects on Social Cognitive and Empathic
Neural Responses.
AB - We aimed to differentiate the neural responses to cooperative and competitive
contexts, which are the two of the most important social contexts in human
society. Healthy male college students were asked to complete a Tetris-like task
requiring mental rotation skills under individual, cooperative, and competitive
contexts in an fMRI scanner. While the participants completed the task, pictures
of others experiencing pain evoking emotional empathy randomly appeared to
capture contextual effects on empathic neural responses. Behavioral results
indicated that, in the presence of cooperation, participants solved the tasks
more accurately and quickly than what they did when in the presence of
competition. The fMRI results revealed activations in the dorsolateral prefrontal
cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) related to executive
functions and theory of mind when participants performed the task under both
cooperative and competitive contexts, whereas no activation of such areas was
observed in the individual context. Cooperation condition exhibited stronger
neural responses in the ventromedial prefrontal cortex (vmPFC) and dmPFC than
competition condition. Competition condition, however, showed marginal neural
responses in the cerebellum and anterior insular cortex (AIC). The two social
contexts involved stronger empathic neural responses to other's pain than the
individual context, but no substantial differences between cooperation and
competition were present. Regions of interest analyses revealed that individual's
trait empathy modulated the neural activity in the state empathy network, the
AIC, and the dorsal anterior cingulate cortex (dACC) depending on the social
context. These results suggest that cooperation improves task performance and
activates neural responses associated with reward and mentalizing. Furthermore,
the interaction between trait- and state-empathy was explored by correlation
analyses between individual's trait empathy score and changing empathic brain
activations along with the exposure to the cooperative and competitive social
contexts.
PMID- 29950979
TI - The Early Facilitative and Late Contextual Specific Effect of the Color Red on
Attentional Processing.
AB - Many studies have proved that color represents a variety of emotionally
meaningful information. Researchers have proposed that context information endows
colors with different associated meanings, and elicits corresponding behavior.
Others have contended that the color red intensifies the stimulus' existing
valence or motivation tendency in the early processing step. The present study
attempts to incorporate these two effects of the color red to explore their
differences in a dot probe task, using event-related potential (ERP). Our ERP
results indicate that the color red intensifies the initial attention to emotion
congruent conditions, as indicated by the P1 component. However, the colors red
and green lead to sustained attention to the expression of anger and happiness,
respectively, but not fear, as shown by the late positive complex component (all
results are available at: https://osf.io/k3b8c/). This study found the different
processing stages of the effect of the color red during attentional processing in
a discrete emotional context, using ERPs, and may refine the Color-in-Context
theory.
PMID- 29950980
TI - Somatotopy in the Human Somatosensory System.
AB - Previous functional magnetic resonance imaging (fMRI) studies have demonstrated
digit somatotopy in primary somatosensory cortex (SI), and even shown that at
high spatial resolution it is possible to resolve within-digit somatotopy.
However, fMRI studies have failed to resolve the spatial organisation of digit
representations in secondary somatosensory cortex (SII). One of the major
limitations of high spatial resolution fMRI studies of the somatosensory system
has been the long acquisition time needed to acquire slices spanning both SI and
SII. Here, we exploit the increased blood oxygenation level dependent contrast of
ultra-high-field (7 Tesla) fMRI and the use of multiband imaging to study the
topographic organisation in SI and SII with high spatial resolution at the
individual subject level. A total of n = 6 subjects underwent vibrotactile
stimulation of their face, hand digits and foot (body imaging) and their
individual hand digits (digit mapping) for each left and right sides of the body.
In addition, n = 2 subjects participated only in the body imaging experiment on
both their left and right sides. We show an orderly representation of the face,
hand digits and foot in contralateral primary cortex in each individual subject.
In SII, there is clear separation of the body areas of the face, hand and foot
but the spatial organisation varies across individual subjects. However, separate
representation of the individual digits of the hand in SII could not be resolved,
even at the spatial resolution of 1.5 mm due to largely overlapping
representations.
PMID- 29950981
TI - Selective Effects of Postural Control on Spatial vs. Nonspatial Working Memory: A
Functional Near-Infrared Spectral Imaging Study.
AB - Background: Previous evidence suggests that postural control processing may be
more related to spatial working memory (SWM) than to nonspatial working memory
(NWM). Methodological discrepancies between spatial and nonspatial cognitive
tasks have made direct comparisons between the two systems difficult. Methods: To
explore the neural mechanisms of SWM and NWM relative to that of postural
control, participants were subjected a cognitive-posture dual-task paradigm,
consisting of a 3-back letter working memory (WM) task, using physically
identical stimuli with spatial and nonspatial components memorized in different
sessions, and a standing balance task with a tandem stance. Additionally, there
were two control sessions: a single-postural control session wherein participants
pressed mouse buttons at random while standing; and a single-cognitive task
control session wherein subjects completed a WM task while seated. The subjects
underwent functional near-infrared spectral imaging (fNIRS) during task
performance, wherein oxygenated hemoglobin concentration ([HbO]) was measured in
frontal and parietal regions. Results: Postural control reduced discernment in
the SWM task significantly, but did not affect NWM task performance. fNIRS showed
that postural control had a significant tendency to decrease the [HbO] in the
frontal-parietal network of the left hemisphere when participants completed the
SWM task. No posture-associated differences in [HbO] were observed in NWM-related
areas during NWM task performance. Behavioral and fNIRS data demonstrated that
postural control had a selective interaction with SWM. Specifically, postural
control reduced SWM discrimination and SWM-related brain activity (frontal
parietal network), but not NWM discrimination or NWM-related brain activity.
Furthermore, the multiple linear regression analysis showed that SWM, but not
NWM, was an important predictor of postural control. These results suggest that
postural control may share more cognitive resources with SWM than with NWM.
PMID- 29950982
TI - Initial Unilateral Exposure to Deep Brain Stimulation in Treatment-Resistant
Depression Patients Alters Spectral Power in the Subcallosal Cingulate.
AB - Background: High-frequency Deep Brain Stimulation (DBS) of the subcallosal
cingulate (SCC) region is an emerging strategy for treatment-resistant depression
(TRD). This study examined changes in SCC local field potentials (LFPs). The LFPs
were recorded from the DBS leads following transient, unilateral stimulation at
the neuroimaging-defined optimal electrode contact. The goal was identifying a
putative electrophysiological measure of target engagement during implantation.
Methods: Fourteen consecutive patients underwent bilateral SCC DBS lead
implantation. LFP recordings were collected from all electrodes during randomized
testing of stimulation on each DBS contact (eight total). Analyses evaluated
changes in spectral power before and after 3 min of unilateral stimulation at the
contacts that later facilitated antidepressant response, as a potential biomarker
of optimal contact selection in each hemisphere. Results: Lateralized and
asymmetric power spectral density changes were detected in the SCC with acute
unilateral SCC stimulation at those contacts subsequently selected for chronic,
therapeutic stimulation. Left stimulation induced broadband ipsilateral decreases
in theta, alpha, beta and gamma bands. Right stimulation effects were restricted
to ipsilateral beta and gamma decreases. These asymmetric effects contrasted with
identical white matter stimulation maps used in each hemisphere. More variable
ipsilateral decreases were seen with stimulation at the adjacent "suboptimal"
contacts, but changes were not statistically different from the "optimal" contact
in either hemisphere despite obvious differences in impacted white matter
bundles. Change in theta power was, however, most robust and specific with left
sided optimal stimulation, which suggested a putative functional biomarker on the
left with no such specificity inferred on the right. Conclusion: Hemisphere
specific oscillatory changes can be detected from the DBS lead with acute
intraoperative testing at contacts that later engender antidepressant effects.
Our approach defined potential target engagement signals for further
investigation, particularly left-sided theta decreases following initial exposure
to stimulation. More refined models combining tractography, bilateral SCC LFP,
and cortical recordings may further improve the precision and specificity of
these putative biomarkers. It may also optimize and standardize the lead
implantation procedure and provide input signals for next generation closed-loop
therapy and/or monitoring technologies for TRD.
PMID- 29950983
TI - CD4+ T Cells Have a Permissive Effect on Enriched Environment-Induced Hippocampus
Synaptic Plasticity.
AB - Living in an enriched environment (EE) benefits health by acting synergistically
on various biological systems including the immune and the central nervous
systems. The dialog between the brain and the immune cells has recently gained
interest and is thought to play a pivotal role in beneficial effects of EE.
Recent studies show that T lymphocytes have an important role in hippocampal
plasticity, learning, and memory, although the precise mechanisms by which they
act on the brain remain elusive. Using a mouse model of EE, we show here that
CD4+ T cells are essential for spinogenesis and glutamatergic synaptic function
in the CA of the hippocampus. However, CD4+ lymphocytes do not influence EE
induced neurogenesis in the DG of the hippocampus, by contrast to what we
previously demonstrated for CD8+ T cells. Importantly, CD4+ T cells located in
the choroid plexus have a specific transcriptomic signature as a function of the
living environment. Our study highlights the contribution of CD4+ T cells in the
brain plasticity and function.
PMID- 29950984
TI - Synaptic Effects of Dopamine Breakdown and Their Relation to Schizophrenia-Linked
Working Memory Deficits.
AB - Working memory is the ability to hold information "online" over a time delay in
order to perform a task. This kind of memory is encoded in the brain by
persistent neural activity that outlasts the presentation of a stimulus. Patients
with schizophrenia perform poorly in working memory tasks that require the brief
memory of a target location in space. This deficit indicates that persistent
neural activity related to spatial locations may be impaired in the disease. At
the circuit level, many studies have shown that NMDA receptors and the dopamine
system are involved in both schizophrenia pathology and working memory-related
persistent activity. In this Hypothesis and Theory article, we examine the
possible connection between NMDA receptors, the dopamine system, and
schizophrenia-linked working memory deficits. In particular, we focus on the
dopamine breakdown product homocysteine (HCY), which is consistently elevated in
schizophrenia patients. Our previous studies have shown that HCY strongly reduces
the desensitization of NMDA currents. Here, we show that HCY likely affects NMDA
receptors in brain regions that support working memory; this is because these
areas favor dopamine breakdown over transport to clear dopamine from synapses.
Finally, within the context of two NMDA-based computational models of working
memory, we suggest a mechanism by which HCY could give rise to the working memory
deficits observed in schizophrenia patients.
PMID- 29950985
TI - Leucine Carboxyl Methyltransferase Downregulation and Protein Phosphatase
Methylesterase Upregulation Contribute Toward the Inhibition of Protein
Phosphatase 2A by alpha-Synuclein.
AB - The pathology of Parkinson's disease (PD) is characterized by intracellular
neurofibrillary tangles of phosphorylated alpha-synuclein (alpha-syn). Protein
phosphatase 2A (PP2A) is responsible for alpha-syn dephosphorylation. Previous
work has demonstrated that alpha-syn can regulate PP2A activity. However, the
mechanisms underlying alpha-syn regulation of PP2A activity are not well
understood. In this study, we found that alpha-syn overexpression induced
increased alpha-syn phosphorylation at serine 129 (Ser129), and PP2A inhibition,
in vitro and in vivo. alpha-syn overexpression resulted in PP2A demethylation.
This demethylation was mediated via downregulated leucine carboxyl
methyltransferase (LCMT-1) expression, and upregulated protein phosphatase
methylesterase (PME-1) expression. Furthermore, LCMT-1 overexpression, or PME-1
inhibition, reversed alpha-syn-induced increases in alpha-syn phosphorylation and
apoptosis. In addition to post-translational modifications of the catalytic
subunit, regulatory subunits are involved in the regulation of PP2A activity. We
found that the levels of regulatory subunits which belong to the PPP2R2
subfamily, not the PPP2R5 subfamily, were downregulated in the examined brain
regions of transgenic mice. Our work identifies a novel mechanism to explain how
alpha-syn regulates PP2A activity, and provides the optimization of PP2A
methylation as a new target for PD treatment.
PMID- 29950987
TI - Cigarette Smoke-Induced Cell Death Causes Persistent Olfactory Dysfunction in
Aged Mice.
AB - Introduction: Exposure to cigarette smoke is a cause of olfactory dysfunction. We
previously reported that in young mice, cigarette smoke damaged olfactory
progenitors and decreased mature olfactory receptor neurons (ORNs), then, mature
ORNs gradually recovered after smoking cessation. However, in aged populations,
the target cells in ORNs by cigarette smoke, the underlying molecular mechanisms
by which cigarette smoke impairs the regenerative ORNs, and the degree of ORN
regeneration after smoking cessation remain unclear. Objectives: To explore the
effects of cigarette smoke on the ORN cell system using an aged mouse model of
smoking, and to investigate the extent to which smoke-induced damage to ORNs
recovers following cessation of exposure to cigarette smoke in aged mice.
Methods: We intranasally administered a cigarette smoke solution (CSS) to 16
month-old male mice over 24 days, then examined ORN existence, cell survival,
changes of inflammatory cytokines in the olfactory epithelium (OE), and olfaction
using histological analyses, gene analyses and olfactory
habituation/dishabituation tests. Results: CSS administration reduced the number
of mature ORNs in the OE and induced olfactory dysfunction. These changes
coincided with an increase in the number of apoptotic cells and Tumor necrosis
factor (TNF) expression and a decrease in Il6 expression. Notably, the reduction
in mature ORNs did not recover even on day 28 after cessation of treatment with
CSS, resulting in persistent olfactory dysfunction. Conclusion: In aged mice, by
increasing ORN death, CSS exposure could eventually overwhelm the regenerative
capacity of the OE, resulting in continued reduction in the number of mature ORNs
and olfactory dysfunction.
PMID- 29950988
TI - The Effect of Quality of Life on Medication Compliance Among Dialysis Patients.
AB - Dialysis treatment is known to lead to reduced quality of life (QOL) among
patients. This decreased QOL is believed to influence medication compliance,
although this effect has not yet been clarified. In this study, we investigated
whether decreased QOL due to dialysis treatment does in fact influence medication
compliance. Participants were 92 patients who self-managed their medication and
were receiving dialysis treatment at Secomedic Hospital or Chiba Central Medical
Center. We surveyed their age, sex, dialysis period, and medication management
situation, and administered the EQ-5D and Kidney Disease Quality of Life
Instrument-Short Form. A multiple logistic regression analysis with medication
compliance as the dependent variable and QOL as the independent variable was
conducted. The recovery rate and effective response rate were both 100%. The
results indicated that patients with good sleep QOL (mean or above) had higher
odds of medication compliance (odds ratio, 3.36; 95% confidence interval, 1.26
8.96; P = 0.016). Therefore, improving the quality of sleep of dialysis patients
might help to improve their medication compliance.
PMID- 29950986
TI - Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving
Cognition in the Aging Brain.
AB - The impact of cognitive aging on brain function and structure is complex, and the
relationship between aging-related structural changes and cognitive function are
not fully understood. Physiological and pathological changes to the aging brain
are highly variable, making it difficult to estimate a cognitive trajectory with
which to monitor the conversion to cognitive decline. Beyond the information on
the structural and functional consequences of cognitive aging gained from brain
imaging and neuropsychological studies, non-invasive brain stimulation techniques
such as transcranial magnetic stimulation (TMS) and transcranial direct current
stimulation (tDCS) can enable stimulation of the human brain in vivo, offering
useful insights into the functional integrity of intracortical circuits using
electrophysiology and neuromodulation. TMS measurements can be used to identify
and monitor changes in cortical reactivity, the integrity of inhibitory and
excitatory intracortical circuits, the mechanisms of long-term potentiation
(LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS
and tDCS can be used to modulate neuronal excitability and enhance cortical
function, and thus offer a potential means to slow or reverse cognitive decline.
This review will summarize and critically appraise relevant literature regarding
the use of TMS and tDCS to probe cortical areas affected by the aging brain, and
as potential therapeutic tools to improve cognitive function in the aging
population. Challenges arising from intra-individual differences, limited
reproducibility, and methodological differences will be discussed.
PMID- 29950989
TI - Andrographolide Inhibits Mechanical and Thermal Hyperalgesia in a Rat Model of
HIV-Induced Neuropathic Pain.
AB - Aim: In this study, we investigated whether andrographolide (Andro) can alleviate
neuropathic pain induced by HIV gp120 plus ddC treatment and the mechanism of its
action. Methods: The paw withdrawal threshold and the paw withdrawal latency were
observed to assess pain behaviors in all groups of the rats, including control
group, control combined with Andro treatment group, sham group, gp120 combined
with ddC treatment group, gp120 plus ddC combined with A438079 treatment group,
and gp120 plus ddC combined with Andro treatment by intrathecally injecting at a
dose of 25 MUg/20 MUl group. The protein expression levels of the P2X7 receptor,
tumor necrosis factor-alpha-receptor (TNFalpha-R), interleukin-1beta (IL-1beta),
IL-10, phospho-extracellular regulated protein kinases (ERK) (p-ERK) in the L4-L6
dorsal root ganglia (DRG) were measured by western blotting. Real-time
quantitative polymerase chain reaction was used to test the mRNA expression level
of the P2X7 receptor. Double-labeling immunofluorescence was used to identify the
co-localization of the P2X7 receptor with glial fibrillary acidic protein (GFAP)
in DRG. Molecular docking was performed to identify whether the Andro interacted
perfectly with the rat P2X7 (rP2X7) receptor. Results: Andro attenuated the
mechanical and thermal hyperalgesia in gp120+ddC-treated rats and down-regulated
the P2X7 receptor mRNA and protein expression in the L4-L6 DRGs of gp120+ddC
treated rats. Additionally, Andro simultaneously decreased the expression of
TNFalpha-R and IL-1beta protein, increased the expression of IL-10 protein in L4
L6 DRGs, and inhibited the activation of ERK signaling pathways. Moreover, Andro
decreased the co-expression of GFAP and the P2X7 receptor in the SGCs of L4-L6
DRG on 14th day after surgery. Conclusion: Andro decreased the hyperalgesia
induced by gp120 plus ddC.
PMID- 29950990
TI - Simvastatin Sensitizes Radioresistant Prostate Cancer Cells by Compromising DNA
Double-Strand Break Repair.
AB - Prostate cancer (PCa) is one of the most prevalent male cancers in western world.
Radiation therapy (RT) is commonly used to treat PCa patients. However, a certain
proportion of patients develop radioresistant PCa cells, which results in
metastatic disease. Statins, which inhibit 3-hydroxy-3-methyl glutaryl coenzyme A
(HMG-CoA) reductase, are commonly used to treat hypercholesterolemia, exhibiting
beneficial effects on cardiovascular diseases and on several types of cancers,
including PCa. However, the mechanistic details and crosstalk between statins and
RT in PCa cells remain unknown. In this study, radioresistant DOC-2/DAB2
interactive protein (DAB2IP)-deficient PCa cells were used to evaluate whether
simvastatin could enhance the effect of ionizing radiation (IR). The crucial
molecules that associated with simvastatin elevated radiosensitivity in PCa cells
were explored. Our results demonstrated that a combination treatment with
simvastatin and IR synergistically induced apoptosis of radioresistant PCa cells.
In addition, simvastatin appeared to compromise DNA double-strand breaks repair
by activating the expressions of histone 2A family member X (gamma-H2AX) and
phospho-checkpoint kinase 1 (p-CHK1), suggesting an underlying mechanism for this
radiosensitization of PCa cells. These findings reveal that simvastatin may be a
potent therapeutic agent for co-treatment with radiation to overcome
radioresistance in PCa cells.
PMID- 29950991
TI - 6'-Hydroxy Justicidin B Triggers a Critical Imbalance in Ca2+ Homeostasis and
Mitochondrion-Dependent Cell Death in Human Leukemia K562 Cells.
AB - Justicia procumbens (J. procumbens) is a traditional Chinese herbal medicine
which was used for the treatment of fever, pain, and cancer. A compound 6'
hydroxy justicidin B (HJB) isolated from J. procumbens exhibits promising
biological properties. However, the mechanism of action and the in vivo behavior
of HJB remain to be elucidated. In this study, we investigated the mechanism of
action of HJB on human leukemia K562 cells and its pharmacokinetic properties in
rats. The results demonstrated that HJB significantly inhibited the proliferation
of K562 cells and promoted apoptosis. Besides, HJB resulted in decreased
mitochondrial membrane potential deltaPSIm, increased the level of the calcium
homeostasis regulator protein TRPC6 and cytosolic calcium. The activity of
caspase-8, caspase-9 and the expression of p53 were significantly increased after
treatment with HJB. Additionally, HJB has rapid absorption rate and relative long
elimination t1/2, indicating a longer residence time in vivo. The results
indicate that HJB inhibited the proliferation of K562 cells and induced apoptosis
by affecting the function of mitochondria and calcium homeostasis to activate the
p53 signaling pathway. The pharmacokinetic study of HJB suggested it is absorbed
well and has moderate metabolism in vivo. These results present HJB as a
potential novel alternative to standard human leukemia therapies.
PMID- 29950992
TI - Icariin Activates Autophagy via Down-Regulation of the NF-kappaB Signaling
Mediated Apoptosis in Chondrocytes.
AB - Osteoarthritis (OA) is a common chronic and degenerative joint condition that is
mainly characterized by cartilage degradation, osteophyte formation, and joint
stiffness. The NF-kappaB signaling pathway in inflammation, autophagy, and
apoptosis plays a prominent role in the progression of OA. Icariin, a prenylated
flavonol glycoside extracted from Epimedium, have been proven to exert anti
osteoporotic and anti-inflammatory effects in OA. However, the action mechanisms
of its effect on chondrocytes have yet to be elucidated. In the present study, we
demonstrated that the in vitro therapeutic effects of icariin on rat chondrocytes
in a dose-dependent manner. We found that TNF-alpha induced the production of IL
1, IL-6, IL-12, reactive oxygen species (ROS), nitric oxide (NO), Caspase-3, and
Caspase-9 in chondrocytes. We also provided evidence that TNF-alpha inhibited
autophagy markers (Atg 5, Atg 7) and prevented LC3 I translate to LC3 II.
Furthermore, TNF-alpha induced matrix metalloproteinase (MMP)3 and MMP9
expression. The negative effects of TNF-alpha on chondrocytes can be partially
blocked by treating with icariin or ammonium pyrrolidinedithiocarbamate (PDTC, an
NF-kappaB inhibitor). The present study data also suggested that icariin
suppressed both TNF-alpha-stimulated p65 nuclear translocation and IkappaBalpha
protein degradation. These results indicated that icariin protected against OA by
suppressing inflammatory cytokines and apoptosis, through activation of autophagy
via NF-kappaB inhibition. In conclusion, icariin appears to favorably modulate
autophagy and apoptosis in chondrocytes making it a promising compound for
cartilage tissue engineering in the treatment of OA.
PMID- 29950993
TI - Transcriptome Profiling Analysis Reveals the Potential Mechanisms of Three
Bioactive Ingredients of Fufang E'jiao Jiang During Chemotherapy-Induced
Myelosuppression in Mice.
AB - Although multiple bioactive components have been identified in Fufang E'jiao
Jiang (FEJ), their hematopoietic effects and molecular mode of action in vivo are
still not fully understood. In the current study, we analyzed the effects of
martynoside, R-notoginsenoside R2 (R2), and 20S-ginsenoside Rg2 (Rg2) in a 5
fluorouracil-induced myelosuppression mouse model. Bone marrow nucleated cells
(BMNCs) counts, hematopoietic progenitor cell colony-forming unit (CFU) assay, as
well as flow cytometry analysis of Lin-/c-kit+/Sca-1+ hematopoietic stem cell
(HSC) population were conducted, and bone marrow cells were subjected to RNA
sequencing. The transcriptome data were processed based on the differentially
expressed genes. The results of the analysis show that each of the three
compounds stimulates BMNCs and HSC growth, as well as burst-forming unit
erythroid and colony-forming unit granulocyte-monocyte colony expansion. The most
relevant transcriptional changes appeared to be involved in regulation of
hematopoietic cell lineage, NF-kappaB and TNF-alpha signaling, inhibition of
inflammation, and acceleration of hematopoietic cell recovery. Notably, the
individual compounds shared similar but specified transcriptome profiles. Taken
together, the hematopoietic effects for the three tested compounds of FEJ are
confirmed in this myelosuppression mouse model. The transcriptome maps of these
effects provide valuable information concerning their underlying mechanisms and
provide a framework for the continued study of the complex mode of action of FEJ.
PMID- 29950994
TI - UPLC/Q-TOFMS-Based Metabolomics Approach to Reveal the Protective Role of Other
Herbs in An-Gong-Niu-Huang Wan Against the Hepatorenal Toxicity of Cinnabar and
Realgar.
AB - An-Gong-Niu-Huang Wan (AGNH) is a well-known traditional Chinese medicine (TCM)
recipe containing cinnabar (HgS) and realgar (As2S2). However, the application of
AGNH is limited by the hepato- and nephrotoxicity of cinnabar and realgar. It
should be noted that cinnabar and realgar in AGNH are not used alone, but rather
combined with other herbs as formula to use. In this study, the protective
effects and mechanisms of the other herbs in AGNH against the hepatorenal
toxicity induced by cinnabar and realgar were investigated. The combination use
of the other herbs in AGNH alleviated inflammatory cell infiltration and damage
in the liver and kidney and restored the disturbed serum metabolic profile
induced by cinnabar and realgar insults. By UPLC/Q-TOFMS combined with pattern
recognition approaches, we identified 41 endogenous metabolites in the sera of
mice that were related to the hepatorenal toxicity of cinnabar and realgar, 36 of
which were restored to normal levels when various kinds of herbs were combined as
compound recipe. These metabolites function as modulators in inflammation
associated glycerophospholipid, arachidonic acid, linoleic acid, sphingolipid,
and ether lipid metabolic pathways. Notably, lysophosphatidylcholines (LysoPCs)
were the most elevated among all of the metabolites detected after cinnabar and
realgar treatment, while these LysoPCs did not show overt differences between the
AGNH and saline control groups, which was associated with relatively unaffected
or even up-regulated expression of lysophosphatidylcholine acyltransferase 1
(LPCAT1) and autotaxin (ATX). These findings indicated that other herbs in AGNH
could have a protective effect against cinnabar- and realgar-induced hepatic and
renal damage via modulating the disordered homeostasis of the
glycerophospholipid, arachidonic acid, linoleic acid, ether lipid, and
sphingolipid metabolism.
PMID- 29950995
TI - Antibacterial Activity and Mechanism of Action of Aspidinol Against Multi-Drug
Resistant Methicillin-Resistant Staphylococcus aureus.
AB - This study aimed at investigating the antibacterial activity of aspidinol, an
extract from Dryopteris fragrans (L.) Schott, against methicillin-resistant
Staphylococcus aureus (MRSA). MRSA isolates were treated with aspidinol to
determine the differential expression of genes and associated pathways following
the drug treatment. Aspidinol displayed significant anti-MRSA activity, both in
vivo (minimum inhibitory concentration = 2 MUg/mL) and in vitro, and achieved an
antibacterial effect comparable to that of vancomycin. In the lethal septicemic
mouse study, a dose of 50 mg/kg of either aspidinol or vancomycin provided
significant protection from mortality. In the non-lethal septicemic mouse study,
aspidinol and vancomycin produced a significant reduction in mean bacterial load
in murine organs, including the spleen, lung, and liver. After treatment with
aspidinol, we found through RNA-seq and RT-PCR experiments that the inhibition of
the formation of ribosomes was the primary S. aureus cell-killing mechanism, and
the inhibition of amino acid synthesis and the reduction of virulence factors
might play a secondary role.
PMID- 29950996
TI - Exploring the Therapeutic Mechanism of Desmodium styracifolium on Oxalate Crystal
Induced Kidney Injuries Using Comprehensive Approaches Based on Proteomics and
Network Pharmacology.
AB - Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb.) Merr (DS)
has been applied clinically to alleviate crystal-induced kidney injuries, but its
effective components and their specific mechanisms still need further
exploration. This research first combined the methods of network pharmacology and
proteomics to explore the therapeutic protein targets of DS on oxalate crystal
induced kidney injuries to provide a reference for relevant clinical use.
Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were
established. Proteins differentially expressed between the oxalate and control
groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The
common differential proteins of the three models were further analyzed by
molecular docking with DS compounds to acquire differential targets. The inverse
docking targets of DS were predicted through the platform of PharmMapper. The
protein-protein interaction (PPI) relationship between the inverse docking
targets and the differential proteins was established by STRING. Potential
targets were further validated by western blot based on a mouse model with DS
treatment. The effects of constituent compounds, including luteolin, apigenin,
and genistein, were investigated based on an oxalate-stimulated HK-2 cell model.
Results: Thirty-six common differentially expressed proteins were identified by
proteomic analysis. According to previous research, the 3D structures of 15 major
constituents of DS were acquired. Nineteen differential targets, including
cathepsin D (CTSD), were found using molecular docking, and the component
differential target network was established. Inverse-docking targets including
p38 MAPK and CDK-2 were found, and the network of component-reverse docking
target was established. Through PPI analysis, 17 inverse-docking targets were
linked to differential proteins. The combined network of component-inverse
docking target-differential proteins was then constructed. The expressions of
CTSD, p-p38 MAPK, and p-CDK-2 were shown to be increased in the oxalate group and
decreased in kidney tissue by the DS treatment. Luteolin, apigenin, and genistein
could protect oxalate-stimulated tubular cells as active components of DS.
Conclusion: The potential targets including the CTSD, p38 MAPK, and CDK2 of DS in
oxalate-induced kidney injuries and the active components (luteolin, apigenin,
and genistein) of DS were successfully identified in this study by combining
proteomics analysis, network pharmacology prediction, and experimental
validation.
PMID- 29950997
TI - Chemical Characterization, Analgesic, Antioxidant, and Anticholinesterase
Potentials of Essential Oils From Isodon rugosus Wall. ex. Benth.
AB - Isodon rugosus Wall. ex. Benth is an important species and is used in folk
medicine for different types of pains such as abdominal pain, earache, toothache,
gastric, and generalized body pain. Recently, we also have reported the
antinociceptive potential of chloroform fraction of I. rugosus. In this research,
we have investigated the antinociceptive, antioxidant and anti-cholinesterase
potentials of essential oils from I. rugosus (Ir.EO), and have determined a
possible mechanism of anti-nociception. The Ir.EO was subjected to gas
chromatography-mass spectroscopy analysis to find out its chemical constituents.
The Ir.EO was assayed for analgesic potential following acetic acid induced
writhing, formalin test and hot plate method in animal models. The antioxidant
activity was conducted against DPPH and ABTS free radicals following
spectroscopic analysis. The cholinesterase inhibitory assays were performed using
Ellman's assay. The GC-MS analysis of Ir.EO revealed the identification of 141
compounds. Ir.EO demonstrated strong antinociceptive potential in all three in
vivo models. With the use of nalaxone, it was confirmed that the essential oil
was acting on the central pathway of nociception. The Ir.EO also exhibited strong
free radicals scavenging potential, exhibiting IC50 values of 338 and 118 MUg/ml
for DPPH and ABTS free radicals respectively. In AChE and BChE inhibitory assays,
the observed IC50 values were 93.56 and 284.19 MUg/ml respectively. The
encouraging antinociceptive, antioxidant and anticholinesterase results revealed
that Ir.EO is a rich source of bioactive compounds as obvious from the GC-MS
results.
PMID- 29950998
TI - Mitochondrial Nicotinic Acetylcholine Receptors Support Liver Cells Viability
After Partial Hepatectomy.
AB - Nicotinic acetylcholine receptors (nAChRs) expressed on the cell plasma membrane
are ligand-gated ion channels mediating fast synaptic transmission, regulating
neurotransmitter and cytokine release and supporting the viability of many cell
types. The nAChRs expressed in mitochondria regulate the release of pro-apoptotic
factors, like cytochrome c, in ion channel-independent manner. Here we show that
alpha3beta2, alpha7beta2, and alpha9alpha10 nAChR subtypes are up-regulated in
rat liver mitochondria 3-6 h after partial hepatectomy resulting in increased
sustainability of mitochondria to apoptogenic effects of Ca2+ and H2O2. In
contrast, laparotomy resulted in down-regulation of all nAChR subunits, except
alpha9, and decreased mitochondria sustainability to apoptogenic effects of Ca2+
and H2O2. Experiments performed in liver mitochondria from alpha3+/-, alpha7-/-,
beta4-/-, alpha7beta2-/-, or wild-type C57Bl/6J mice demonstrated that the
decrease of alpha3 or absence of alpha7 or alpha7/beta2 subunits in mitochondria
is compensated with beta4 and alpha9 subunits, which could be found in
alpha3beta4, alpha4beta4, alpha9beta4, and alpha9alpha10 combinations.
Mitochondria from knockout mice maintained their sustainability to Ca2+ but were
differently regulated by nAChR subtype-specific ligands: PNU-282987,
methyllycaconitine, dihydro-beta-erythroidine, alpha-conotoxin MII, and alpha
conotoxin PeIA. It is concluded that mitochondrial nAChRs play an important role
in supporting the viability of hepatic cells and, therefore, may be a
pharmacological target for pro-survival therapy. The concerted action of multiple
nAChR subtypes controlling either CaKMII- or Src-dependent signaling pathways in
mitochondria ensures a reliable protection against apoptogenic factors of
different nature.
PMID- 29950999
TI - Cell Cycle Arrest and Apoptosis in HT-29 Cells Induced by Dichloromethane
Fraction From Toddalia asiatica (L.) Lam.
AB - The roots of Toddalia asiatica (L.) Lam. (TA) has been often used in Chinese folk
medicine to treat different diseases, including but not limited to arthritis,
injuries, stomachache, and even tumors. However, the anti-cancer effects and the
action mechanisms of TA remain elusive. Therefore, we firstly evaluated the
effects of different extracts of TA on the growth of human colon cancer cells,
and then tried to further elucidate their underlying molecular mechanisms. As a
result, the dichloromethane fraction (DF) was found to possess the highest anti
proliferative activity with IC50 value at 18 MUg/mL among all of the four
extracts from TA, and strongly inhibited HT-29 cell growth and halted cell cycle
progression in G2/M phase. DF also induced phosphatidylserine externalization and
activated caspases -8, -9, and -3, suggesting DF induced apoptosis through
intrinsic and extrinsic pathways. Furthermore, we found that HT-29 cell cycle
arrest induced by DF could be the result of reactive oxygen species (ROS), as the
ROS scavenger N-acetyl cysteine (NAC) attenuating it. Taken together, these
results indicated that DF induced cell cycle arrest at G2/M phase and apoptosis
in HT-29 cells, and could be a promising source for developing natural
therapeutics for colon cancer.
PMID- 29951000
TI - Corrigendum: Chronic MK-801 Application in Adolescence and Early Adulthood: A
Spatial Working Memory Deficit in Adult Long-Evans Rats But No Changes in the
Hippocampal NMDA Receptor Subunits.
AB - [This corrects the article on p. 42 in vol. 9, PMID: 29487522.].
PMID- 29951001
TI - In Silico Analysis Identifies Intestinal Transit as a Key Determinant of Systemic
Bile Acid Metabolism.
AB - Bile acids fulfill a variety of metabolic functions including regulation of
glucose and lipid metabolism. Since changes of bile acid metabolism accompany
obesity, Type 2 Diabetes Mellitus and bariatric surgery, there is great interest
in their role in metabolic health. Here, we developed a mathematical model of
systemic bile acid metabolism, and subsequently performed in silico analyses to
gain quantitative insight into the factors determining plasma bile acid
measurements. Intestinal transit was found to have a surprisingly central role in
plasma bile acid appearance, as was evidenced by both the necessity of detailed
intestinal transit functions for a physiological description of bile acid
metabolism as well as the importance of the intestinal transit parameters in
determining plasma measurements. The central role of intestinal transit is
further highlighted by the dependency of the early phase of the dynamic response
of plasma bile acids after a meal to intestinal propulsion.
PMID- 29951002
TI - Thoracoabdominal Asynchrony Contributes to Exercise Limitation in Mild Asthmatic
Subjects.
AB - This study aimed to better understand how subjects with stable asthma and without
exercise-induced bronchoconstriction respond to mild exercise. Breathing pattern,
chest wall compartmental and operational volumes, and thoracoabdominal asynchrony
were assessed in 11 stable asthmatic subjects and 10 healthy subjects at rest and
during exercise in a cycle-ergometer through optoelectronic plethysmography.
Dyspnea and sensation of leg effort were assessed through Borg scale. During
exercise, with similar minute ventilation, a significant lower chest wall tidal
volume (p = 0.003) as well as a higher respiratory rate (p < 0.05) and rapid
shallow breathing (p < 0.05) were observed in asthmatic when compared to healthy
subjects. Asthmatic subjects exhibited a significantly lower inspiratory (p <
0.05) and expiratory times (p < 0.05). Intergroup analysis found a significant
higher end-expiratory chest wall volume in asthmatic subjects, mainly due to a
significant increase in volume of the pulmonary ribcage (RCp; 170 ml, p = 0.002),
indicating dynamic hyperinflation (DH). Dyspnea and sensation of leg effort were
both significantly greater (p < 0.0001) in asthmatic when compared to healthy
subjects. In addition to a higher thoracoabdominal asynchrony found between RCp
and abdominal (AB) (p < 0.005) compartments in asthmatic subjects, post
inspiratory action of the inspiratory ribcage and diaphragm muscles were observed
through the higher expiratory paradox time of both RCp (p < 0.0001) and AB (p =
0.0002), respectively. Our data suggest that a different breathing pattern is
adopted by asthmatic subjects without exercise-induced bronchoconstriction during
mild exercise and that this feature, associated with DH and thoracoabdominal
asynchrony, contributes significantly to exercise limitation.
PMID- 29951003
TI - Functional Exercise Training and Undulating Periodization Enhances the Effect of
Whole-Body Electromyostimulation Training on Running Performance.
AB - The popularity of whole-body electromyostimulation is growing during the last
years, but there is a shortage of studies that evaluate its effects on physical
fitness and sport performance. In this study, we compared the effects of a
periodized and functional whole-body-electromyostimulation training on maximum
oxygen uptake (VO2max), ventilatory thresholds (VT1 and VT2), running economy
(RE), and lower-body muscle strength in runners, vs. a traditional whole-body
electromyostimulation training. A total of 12 male recreational runners, who had
been running 2-3 times per week (90-180 min/week) for at least the previous year
and had no previous experience on WB-EMS training, were enrolled in the current
study. They were randomly assigned to a periodized and functional whole-body
electromyostimulation training group (PFG) (n = 6; 27.0 +/- 7.5 years; 70.1 +/-
11.1 kg; 1.75 +/- 0.05 m) whose training program involved several specific
exercises for runners, or a traditional whole-body-electromyostimulation training
group (TG) (n = 6; 25.8 +/- 7.4 years; 73.8 +/- 9.8 kg; 1.73 +/- 0.07 m), whose
sessions were characterized by circuit training with 10 dynamic and general
exercises without external load. The training programs consisted of one whole
body electromyostimulation session and one 20-min running session per week,
during 6 weeks. The PFG followed an undulating periodization model and a
selection of functional exercises, whereas the TG followed a traditional session
structure used in previous studies. Both groups were instructed to stop their
habitual running training program. VO2max, VT1, VT2, RE, and lower body muscle
strength (vertical jump) were measured before and after the intervention. The PFG
obtained significantly higher improvements when compared with the TG in terms of
VO2max (2.75 +/- 0.89 vs. 1.03 +/- 1.01 ml/kg/min, P = 0.011), VT2 (2.95 +/- 1.45
vs. 0.35 +/- 0.85 ml/kg/min, P = 0.005), VO2max percentage at VT2 (5.13 +/- 2.41
vs. 0.63 +/- 1.61%), RE at VT1 (-7.70 +/- 2.86 vs. -3.50 +/- 2.16 ml/kg/km, P =
0.048), RE at 90% of VT2 (-15.38 +/- 4.73 vs. -3.38 +/- 4.11 ml/kg/km, P =
0.005), and vertical jump in Abalakov modality (2.95 +/- 0.94 vs. 0.52 +/- 1.49
cm, P = 0.008). Therefore, we conclude that running performance improvements were
better after a 6-week program following an undulating periodization and
consisting on functional exercises when compared with a 6-week traditional WB-EMS
program.
PMID- 29951004
TI - Detection of Life Threatening Ventricular Arrhythmia Using Digital Taylor Fourier
Transform.
AB - Accurate detection and classification of life-threatening ventricular arrhythmia
episodes such as ventricular fibrillation (VF) and rapid ventricular tachycardia
(VT) from electrocardiogram (ECG) is a challenging problem for patient monitoring
and defibrillation therapy. This paper introduces a novel method for detection
and classification of life-threatening ventricular arrhythmia episodes. The ECG
signal is decomposed into various oscillatory modes using digital Taylor-Fourier
transform (DTFT). The magnitude feature and a novel phase feature namely the
phase difference (PD) are evaluated from the mode Taylor-Fourier coefficients of
ECG signal. The least square support vector machine (LS-SVM) classifier with
linear and radial basis function (RBF) kernels is employed for detection and
classification of VT vs. VF, non-shock vs. shock and VF vs. non-VF arrhythmia
episodes. The accuracy, sensitivity, and specificity values obtained using the
proposed method are 89.81, 86.38, and 93.97%, respectively for the classification
of Non-VF and VF episodes. Comparison with the performance of the state-of-the
art features demonstrate the advantages of the proposition.
PMID- 29951005
TI - Corrigendum: MicroRNA-200a/200b Modulate High Glucose-Induced Endothelial
Inflammation by Targeting O-linked N-Acetylglucosamine Transferase Expression.
AB - [This corrects the article on p. 355 in vol. 9, PMID: 29720943.].
PMID- 29951006
TI - Stress Induced Hormone and Neuromodulator Changes in Menopausal Depressive Rats.
AB - Objective: Previously, we showed that neuromodulators are important factors
involved in depression, here we aim to further investigate the interactions
between neuromodulators and sex hormone involved in menopause related depression
in rats. Methods: Menopausal depression was made with bilateral ovariectomies in
female SD rats followed by chronic mild unpredictable stress treatment for 21
days. Thirty six rats were randomly divided into four groups: sham surgery group,
sham/stress group, surgery group, surgery/stress group. Then open-field locomotor
scores and sucrose intake were employed to observe behavior changes. The levels
of norepinephrine (NE), dopamine (DA), serotonin (5-HT) in the cerebral spinal
fluid and serum adrenocorticotropic hormone (ACTH), cortisone were determined
with High-performance liquid chromatography (HPLC). Serum estradiol (E2),
follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured
with radioimmunoassay. Results: The open-field locomotor scores and sucrose
intake were significantly decreased after the surgery and stress treatment (p <
0.01). The Serum E2 level decreased significantly after the surgery (p < 0.01),
but serum LH, FSH levels increased significantly in the surgery group than the
sham surgery group (p < 0.01). The cortisone levels increased significantly in
sham/stress group than that in the sham surgery group during the first 2 weeks at
stressful treatment, but decrease afterwards. The monoamine levels in the
surgery/stress group were much lower than those in the sham surgery group (p <
0.01). The correlation analysis found that LH and FSH are related more to the
neurotransmitter release than E2. Conclusion: Ovary removal rats showed
depression-like behaviors, with LH and FSH increase and monoamine decrease, and
the levels of these monoamines in the stress treated groups changed only after
the stressful treatment. The LH, FSH hormone increasing might be the reason for
the lower monoamine release, which in turn might be the reason for depressed
syndromes in the menopause. The cortisone and ACTH in the serum in the
surgery/stress group were much higher than that in the sham surgery group.
PMID- 29951007
TI - Increased Default Mode Network Connectivity in Obsessive-Compulsive Disorder
During Reward Processing.
AB - Objective: Obsessive-compulsive disorder (OCD) is characterized by anxiety
provoking, obsessive thoughts (i.e., obsessions) which patients react to with
compulsive behaviors (i.e., compulsions). Due to the transient feeling of relief
following the reduction of obsession-induced anxiety, compulsions are often
described as relieving or even rewarding. Several studies investigated functional
activation during reward processing in OCD, but findings are heterogeneous up to
now and little is known about potential alterations in functional connectivity.
Method: Against this background we studied OCD patients (n = 44) and healthy
controls (n = 37) during the receipt of monetary reward by assessing both
activation and functional connectivity. Results: Patients showed a decreased
activation in several frontal regions and the posterior cingulate (PCC, BA31)
together with a stronger connectivity between the PCC and the vmPFC (BA10).
Conclusion: Present findings demonstrate an increased connectivity in patients
within major nodes of the default mode network (DMN)-a network known to be
involved in the evaluation of internal mental states. These results may indicate
an increased activity of internal, self-related processing at the expense of a
normal responsiveness toward external rewards and incentives. This, in turn, may
explain the constant urge for additional reinforcement and patients' inability to
inhibit their compulsive behaviors.
PMID- 29951008
TI - Electrophysiological Evidence in Schizophrenia in Relation to Treatment Response.
AB - Several domains of cognitive function, e.g., verbal memory, information
processing, fluency, attention, and executive function are impaired in patients
with schizophrenia. Cognitive impairments in schizophrenia have attracted
interests as a treatment target, because they are considered to greatly affect
functional outcome. Electrophysiological markers, including electroencephalogram
(EEG), particularly, event-related potentials, have contributed to psychiatric
research and clinical practice. In this review, we provide a summary of studies
relating electrophysiological findings to cognitive performance in schizophrenia.
Electrophysiological indices may provide an objective marker of cognitive
processes, contributing to the development of effective interventions to improve
cognitive and social outcomes. Further efforts to understand biological
mechanisms of cognitive disturbances, and develop effective therapeutics are
warranted.
PMID- 29951009
TI - Self-Distancing Reduces Probability-Weighting Biases.
AB - We have abundant evidence that people exhibit biases in weighting probability
information. The current study aims to examine whether self-distancing would
reduce these biases. Participants in this study were instructed to use either a
self-distancing or a self-immersing strategy to regulate their reasoning when
they indicated their valuations of different lotteries. The results show that,
compared to the baseline group, participants in the self-distancing group
exhibited less distortion in the probability-weighting function, while those in
the self-immersing group exhibited more distortion. These results offer evidence
for the power of self-distancing in reducing probability-weighting biases.
PMID- 29951011
TI - The Use of Problem-Solving Therapy for Primary Care to Enhance Complex Decision
Making in Healthy Community-Dwelling Older Adults.
AB - Some older adults who are cognitively healthy have been found to make poor
decisions. The vulnerability of such older adults has been postulated to be the
result of disproportionate aging of the frontal lobes that contributes to a
decline in executive functioning abilities among some older adults. The purpose
of this study was to investigate whether decision-making performance in older
adults can be enhanced by a psychoeducational intervention. Twenty cognitively
and emotionally intact persons aged 65 years and older were recruited and
randomized into two conditions: psychoeducational condition [Problem-Solving
Therapy for Primary Care (PST-PC)] and no-treatment Control group. Participants
in the psychoeducational condition each received four 45-min sessions of PST-PC
across a 2-week period. The Iowa Gambling Task (IGT) was administered as the
outcome measure to the treatment group, while participants in the Control group
completed the IGT without intervention. A significant interaction effect was
observed between group status and the trajectory of score differences across
trials on the IGT. Particularly, as the task progressed to the last 20% of
trials, participants in the PST-PC group significantly outperformed participants
in the Control group in terms of making more advantageous decisions. These
findings demonstrated that a four-session problem-solving therapy can reinforce
aspects of executive functioning (that may have declined as a part of healthy
aging), thereby enhancing complex decision-making in healthy older adults.
PMID- 29951012
TI - Probability-of-Superiority SEM (PS-SEM)-Detecting Probability-Based Multivariate
Relationships in Behavioral Research.
AB - In behavioral research, exploring bivariate relationships between variables X and
Y based on the concept of probability-of-superiority (PS) has received increasing
attention. Unlike the conventional, linear-based bivariate relationship (e.g.,
Pearson's correlation), PS defines that X and Y can be related based on their
likelihood-e.g., a student who is above mean in SAT has 63% likelihood of
achieving an above-mean college GPA. Despite its increasing attention, the
concept of PS is restricted to a simple bivariate scenario (X-Y pair), which
hinders the development and application of PS in popular multivariate modeling
such as structural equation modeling (SEM). Therefore, this study addresses an
empirical-based simulation study that explores the potential of detecting PS
based relationship in SEM, called PS-SEM. The simulation results showed that the
proposed PS-SEM method can detect and identify PS-based when data follow PS-based
relationships, thereby providing a useful method for researchers to explore PS
based SEM in their studies. Conclusions, implications, and future directions
based on the findings are also discussed.
PMID- 29951010
TI - Parental Decision-Making on Childhood Vaccination.
AB - A growing number of parents delay vaccinations or are deciding not to vaccinate
their children altogether. This increases the risk of contracting vaccine
preventable diseases and disrupting herd immunity, and also impairs the trust in
the capacities of health care systems to protect people. Vaccine hesitancy is
related to a range of both psychological and demographic determinants, such as
attitudes toward vaccinations, social norms, and trust in science. Our aim is to
understand those determinants in parents, because they are a special group in
this issue-they act as proxy decision makers for their children, who are unable
to decide for themselves. The fact that deciding to vaccinate is a socially
forced choice that concerns a child's health makes vaccine-related decisions
highly important and involving for parents. This high involvement might lead to
parents overemphasizing the potential side effects that they know to be vaccine
related, and by amplifying those, parents are more focused on the potential
outcomes of vaccine-related decisions, which can yield specific pattern of the
outcome bias. We propose two related studies to investigate factors which promote
vaccine hesitancy, protective factors that determine parental vaccination
decisions, and outcome bias in parental vaccination intentions. We will explore
demographic and psychological factors, and test parental involvement related to
vaccine hesitancy using an online battery in a correlation panel design study.
The second study is an experimental study, in which we will investigate the
moderating role of parents' high involvement in the specific domain of
vaccination decision making. We expect that higher involvement among parents,
compared to non-parents, will shape the pattern of the proneness to outcome bias.
The studies will be conducted across eight countries in Europe and Asia (Finland,
Germany, Hong Kong, the Netherlands, Serbia, Slovenia, Spain, and the United
Kingdom), rendering findings that will aid with understanding the underlying
mechanisms of vaccine hesitancy and paving the way for developing interventions
custom-made for parents.
PMID- 29951013
TI - Returning Serve in Tennis: A Qualitative Examination of the Interaction of
Anticipatory Information Sources Used by Professional Tennis Players.
AB - Research has largely focused on the individual contribution of either kinematic
or contextual information sources to the anticipatory skill of an expert athlete
during a time-stressed situation. Very little research has considered how these
two sources of information interact with each other to influence anticipation.
The current study used a qualitative interview methodology to investigate this
interaction. Eight former or current top 250 professional male tennis players
participated in a 30-60 min interview about the interaction of kinematic and
contextual information sources and their influence on anticipation. Using an open
coding analysis approach, codes were identified by each researcher from the
transcribed interviews and then brought together to identify common themes. The
primary themes were consciousness, tactical awareness, contextual information
sources, kinematic information sources, mentality/confidence, returner technique
or strategy, and build pressure on the server. Secondary themes coded from the
participants were returning characteristics and practice. Consequently, a
temporal model was developed which demonstrated the sequence and interaction of
both kinematic and contextual information sources known to influence expert
tennis player's anticipation.
PMID- 29951014
TI - Cognitive Aspects of Comb-Building in the Honeybee?
AB - The wax-made comb of the honeybee is a masterpiece of animal architecture. The
highly regular, double-sided hexagonal structure is a near-optimal solution to
storing food and housing larvae, economizing on building materials and space.
Elaborate though they may seem, such animal constructions are often viewed as the
result of 'just instinct,' governed by inflexible, pre-programmed, innate
behavior routines. An inspection of the literature on honeybee comb construction,
however, reveals a different picture. Workers have to learn, at least in part,
certain elements of the technique, and there is considerable flexibility in terms
of how the shape of the comb and its gradual manufacture is tailored to the
circumstances, especially the available space. Moreover, we explore the 2-century
old and now largely forgotten work by Francois Huber, where glass screens were
placed between an expanding comb construction and the intended target wall. Bees
took corrective action before reaching the glass obstacle, and altered the
ongoing construction so as to reach the nearest wooden wall. Though further
experiments will be necessary, these results suggest a form of spatial planning
skills. We discuss these findings in the context of what is now known about
insect cognition, and ask if it is possible that the production of hexagonal wax
combs is the result of behavioral heuristics where a complex structure emerges as
the result of simple behavioral rules applied by each individual, or whether
prospective cognition might be involved.
PMID- 29951015
TI - Believing What You're Told: Politeness and Scalar Inferences.
AB - The experimental pragmatics literature has extensively investigated the ways in
which distinct contextual factors affect the computation of scalar inferences,
whose most studied example is the one that allows "Some X-ed" to mean Not all X
ed. Recent studies from Bonnefon et al. (2009, 2011) investigate the effect of
politeness on the interpretation of scalar utterances. They argue that when the
scalar utterance is face-threatening ("Some people hated your speech") (i) the
scalar inference is less likely to be derived, and (ii) the semantic
interpretation of "some" (at least some) is arrived at slowly and effortfully.
This paper re-evaluates the role of politeness in the computation of scalar
inferences by drawing on the distinction between "comprehension" and "epistemic
assessment" of communicated information. In two experiments, we test the
hypothesis that, in these face-threatening contexts, scalar inferences are
largely derived but are less likely to be accepted as true. In line with our
predictions, we find that slowdowns in the face-threatening condition are
attributable to longer reaction times at the (latter) epistemic assessment stage,
but not at the comprehension stage.
PMID- 29951016
TI - Corrigendum: Applicability of the Compensatory Encoding Model in Foreign Language
Reading: An Investigation With Chinese College English Language Learners.
AB - [This corrects the article on p. 681 in vol. 8, PMID: 28522984.].
PMID- 29951017
TI - Guided Embodiment and Potential Applications of Tutor Systems in Language
Instruction and Rehabilitation.
AB - Intelligent tutor systems (ITSs) in mobile devices take us through learning tasks
and make learning ubiquitous, autonomous, and at low cost (Nye, 2015). In this
paper, we describe guided embodiment as an ITS essential feature for second
language learning (L2) and aphasia rehabilitation (ARe) that enhances efficiency
in the learning process. In embodiment, cognitive processes, here specifically
language (re)learning are grounded in actions and gestures (Pecher and Zwaan,
2005; Fischer and Zwaan, 2008; Dijkstra and Post, 2015). In order to guide users
through embodiment, ITSs must track action and gesture, and give corrective feed
back to achieve the users' goals. Therefore, sensor systems are essential to
guided embodiment. In the next sections, we describe sensor systems that can be
implemented in ITS for guided embodiment.
PMID- 29951018
TI - Examining the Relationship Between Teachers' ICT Self-Efficacy for Educational
Purposes, Collegial Collaboration, Lack of Facilitation and the Use of ICT in
Teaching Practice.
AB - Information and communication technology (ICT) is now an integrated and central
element of modern life, and its rapid emergence is changing the execution and
organization of work and learning. Digital technology is also important for
schools, and hence for teachers' working days. However, among today's teachers,
not everyone has the knowledge required to teach using digital technology. Recent
research indicates that self-efficacy is important for how teachers master their
practice. This paper addresses teachers' ICT self-efficacy for educational
purposes, and examines the assumed antecedents of teachers' self-efficacy. Data
from 1,158 teachers at 116 Norwegian schools was analyzed. The results indicate
that teachers' self-efficacy for using ICT in their teaching practice is
associated with their use of ICT in teaching and their general ICT self-efficacy.
In addition, the results show that collegial collaboration among teachers has a
positive association with the use of ICT in their teaching practice. One
interpretation of these findings is that general ICT self-efficacy is necessary
for developing ICT self-efficacy for educational purposes and being able to use
ICT in education. However, further research is required to scrutinize the
relationships between these concepts.
PMID- 29951019
TI - Sex Hormones Are Associated With Rumination and Interact With Emotion Regulation
Strategy Choice to Predict Negative Affect in Women Following a Sad Mood
Induction.
AB - Women are particularly vulnerable to anxiety and depressive disorders. This
greater vulnerability has been partly attributed to post-pubertal sex hormone
fluctuations, estradiol and progesterone, as well as gender-specific tendencies
to engage in maladaptive forms of emotion regulation, particularly rumination. To
date, no research has investigated whether sex hormones are associated with
emotion regulation in women. In the present study, 61 women participated in a sad
mood induction task, involving the viewing of an emotive film. Negative affect
was assessed immediately and following recovery, along with self-reported use of
rumination, reappraisal, and suppression. Serum levels of estradiol and
progesterone were assessed through a blood sample taken at the end of the
experiment. Regression analyses were used to examine the relationship between
serum hormones and self-reported emotional regulation strategy use, and between
serum hormones and the impact of these strategies on negative affect. Estradiol
levels positively predicted rumination, but not suppression or reappraisal use.
Moreover, estradiol and progesterone interacted with emotion regulation
strategies to predict negative affect following the sad mood induction.
Reappraisal was associated with greater negative affect only in women with high
estradiol, and in women with high progesterone. Conversely, rumination was
associated with greater negative affect only in women with low estradiol.
Together, these results suggest that sex hormone concentration may be an
endogenous contextual factor that is associated with the selection and
consequences of emotion regulation strategies in women.
PMID- 29951021
TI - Spanish Validation of the Shorter Version of the Workplace Incivility Scale: An
Employment Status Invariant Measure.
AB - Workplace Incivility (WI) occurs worldwide and has negative consequences on
individuals and organizations. Valid and comprehensive instruments have been
used, specifically in English speaking countries, to measure such adverse process
at work, but it is not available a validated instrument for research carried out
in Spanish speaking countries. In this study we aim to test the psychometric
properties of the Matthews and Ritter's four-item Workplace Incivility Scale
(2016) with Spanish workers (N = 407) from different sectors. Participants' mean
age was 38.73 (SD = 10.45) years old and the percentage of female employees was
59.2%. Confirmatory factor analysis using AMOS 19.0 was carried out, presenting a
good fit. The internal consistency, convergent and concurrent validity of the
scale were examined. Results show good scale reliability and expected high
correlations with social undermining. Moreover, the scale related to propensity
to leave a job, job satisfaction, and psychological well-being in the expected
way. After configural invariance across groups was established, testing for
metric invariance and scalar invariance was performed. Considering Deltachi2 and
DeltaCFI tests for two nested models, the 4-item scale was invariant when the
employment status is considered (permanent vs. temporal, full-time vs. part-time,
and supervisor vs. non-supervisors). Overall, our findings showed good
psychometric properties of the shorter version of the WIS in Spain. Theoretical
and practical implications of this study are discussed.
PMID- 29951020
TI - Profiles of Cognitive-Motor Interference During Walking in Children: Does the
Motor or the Cognitive Task Matter?
AB - The evidence supporting the effects of age on the ability to coordinate a motor
and a cognitive task show inconsistent results in children and adolescents, where
the Dual-Task Effects (DTE) - if computed at all - range from either being lower
or comparable or higher in younger children than in older children, adolescents
and adults. A feasible reason for the variability in such findings is the wide
range of cognitive tasks (and to some extend of motor tasks) used to study
Cognitive-Motor Interference (CMI). Our study aims at determining the differences
in CMI when performing cognitive tasks targeting different cognitive functions at
varying walking pathways. 69 children and adolescents (boys, n = 45; girls, n =
24; mean age, 11.5 +/- 1.50 years) completed higher-level executive function
tasks (2-Back, Serial Subtraction, Auditory Stroop, Clock Task, TMT-B) in
comparison to non-executive distracter tasks [Motor Response Task (MRT), TMT-A]
to assess relative effects on gait during straight vs. repeated Change of
Direction (COD) walking. DT during COD walking was assessed using the Trail
Walking-Test (TWT). The motor and cognitive DTE were calculated for each task.
There were significant differences between 5th and 8th graders on single gait
speed on the straight (p = 0.016) and the COD pathway (p = 0.023), but not on any
of the DT conditions. The calculation of DTEs revealed that motor DTEs were
lowest for the MRT and highest for the TWT in the numbers/letters condition (p <
0.05 for all comparisons). In contrast, there were cognitive benefits for the
higher-order cognitive tasks on the straight pathways, but cognitive costs for
both DT conditions on the COD pathway (p < 0.01 for all comparisons). Our
findings demonstrate that DT changes in walking when completing a secondary task
that involve higher-level cognition are attributable to more than low-level
divided attention or motor response processes. These results specifically show
the direct competition for higher-level executive function resources important
for walking, and are in agreement with previous studies supporting the cognitive
motor link in relation to gait in children. This might be in line with the idea
that younger children may not have adequate cognitive resources.
PMID- 29951022
TI - On the Effects of Ethical Climate(s) on Employees' Behavior: A Social Identity
Approach.
AB - The spread and publicity given to questionable practices in the corporate world
during the last two decades have fostered an increasing interest about the
importance of ethical work for organizations, practitioners, scholars and, last
but not least, the wider public. Relying on the Social Identity Approach, we
suggest that the effects of different ethical climates on employee behaviors are
driven by affective identification with the organization and, in parallel, by
cognitive moral (dis)engagement. We compared the effects of two particular
ethical climates derived from the literature: An ethical organizational climate
of self-interest, and an ethical organizational climate of friendship. Three
hundred seventy-six workers completed measures of Ethical Climate, Organizational
Identification, Moral Disengagement, Organizational Citizenship Behaviors (OCBs),
and Counterproductive Work Behaviors (CWBs). Structural equation modeling
confirmed that the two ethical climates considered were independently related to
organizational identification and moral disengagement. These, in turn, mediated
the effects of ethical climates on OCBs and CWBs. We discuss results in light of
the social identity approach, and present some practical implications of our
findings.
PMID- 29951023
TI - On the Importance of the Speed-Ability Trade-Off When Dealing With Not Reached
Items.
AB - In many applications of high- and low-stakes ability tests, a non-negligible
amount of respondents may fail to reach the end of the test within the specified
time limit. Since for respondents that ran out of time some item responses will
be missing, this raises the question of how to best deal with these missing
responses for the purpose of obtaining an optimal assessment of ability.
Commonly, researchers consider three general solutions: ignore the missing
responses, treat them as being incorrect, or treat the responses as missing but
model the missingness mechanism. This paper approaches the issue of dealing with
not reached items from a measurement perspective, and considers the question what
the operationalization of ability should be in maximum performance tests that
work with effective time limits. We argue that the target ability that the test
attempts to measure is maximum performance when operating at the test-indicated
speed, and that the test instructions should be taken to imply that respondents
should operate at this target speed. The phenomenon of the speed-ability trade
off informs us that the ability that is measured by the test will depend on this
target speed, as different speed levels will result in different levels of
performance on the same set of items. Crucially, since respondents with not
reached items worked at a speed level lower than this target speed, the level of
ability that they have been able to display on the items that they did reach is
higher than the level of ability that they would have displayed if they had
worked at the target speed (i.e., higher than their level on the target ability).
Thus, statistical methods that attempt to obtain unbiased estimates of the
ability as displayed on the items that were reached will result in biased
estimates of the target ability. The practical implications are studied in a
simulation study where different methods of dealing with not reached items are
contrasted, which shows that current methods result in biased estimates of target
ability when a speed-ability trade-off is present. The paper concludes with a
discussion of ways in which the issue can be resolved.
PMID- 29951024
TI - Does Work-Family Conflict Mediate the Associations of Job Characteristics With
Employees' Mental Health Among Men and Women?
AB - Job characteristics are important to work-family conflict (WFC). Additionally, is
well established that WFC has a negative impact on mental health. As such, this
research aims to examine the role of WFC as a mechanism that explains the
relationship between job characteristics (i.e., those establishing by the Job
Demands-Control-Support Model) and workers' mental health. Moreover, based on
gender inequalities in work and non-work roles, this study analyzed gender as
moderator of this mediation. Specifically, the relationship between job
characteristics and WFC and the relationship between WFC and mental health could
be stronger for women than for men. With a sample of 254 workers from a
Portuguese services company, (61% males), and based on a multiple-group analysis,
the results indicated that the WFC mediates the relationship between job
characteristics (i.e., job demands and job control) and mental health. It was
reinforced that job demands and lack of control could contribute to employees'
stress and, once individual' energy was drained, the WFC could emerge.
Ultimately, may be due to the presence of this conflict that individuals mental
health' is negatively affected. Contrary to our expectations, this relationship
is not conditioned by gender (Z-scores were non-significant). The study results
have implications for human resource management, enhancing the knowledge on the
relationship between the WFC and workers' mental health.
PMID- 29951025
TI - Editorial: New Boundaries Between Aging, Cognition, and Emotions.
PMID- 29951026
TI - Warnings to Counter Choice Blindness for Identification Decisions: Warnings Offer
an Advantage in Time but Not in Rate of Detection.
AB - Choice blindness for identification decisions refers to the inability of
eyewitnesses to detect that an originally recognized target was swapped for a non
identified lineup member. The robustness of the effect calls for measures that
can prevent or reduce the negative consequences of choice blindness
manipulations. Here, we investigated whether pre- and post-warnings given to
participants about the possibility of mistakes reduces choice blindness for
identification decisions. Participants (N = 119) were presented with
identifications they never made and were asked to justify those decisions. Either
before or after the presentation of the manipulated identification outcome,
participants were or were not warned about the possibility of mistakes in the
identification process. Although warnings were not sufficient to reduce choice
blindness for identification decisions they provided a time-related detection
advantage. Pre-warned participants questioned the legitimacy of the manipulated
outcome sooner (i.e., concurrent detection) than participants in other
conditions. Hence, pre-warnings can help detect mistakes in the identification
procedure at an earlier stage, before they contaminate the memory of the witness
and other pieces of evidence. From a theoretical stance, our findings attest to
the strength of self-suggestion and indicate that choice blindness effects are
deeply rooted in cognition.
PMID- 29951027
TI - Mindfulness Training for People With Dementia and Their Caregivers: Rationale,
Current Research, and Future Directions.
AB - The world population is aging and the prevalence of dementia is increasing. By
2050, those aged 60 years and older are expected to make up a quarter of the
population. With that, the number of people with dementia is increasing.
Unfortunately, there is no cure for dementia. The progression of symptoms with no
hope of improvement is difficult to cope with, both for patients and their
caregivers. New and evidence-based strategies are needed to support the well
being of both caregiver and patient. Mindfulness training is a body-mind
intervention that has shown to improve psychological well-being in a variety of
mental health conditions. Mindfulness, a non-judgmental attention to one's
experience in the present moment, is a skill that can be developed with a
standard 8-week training. Research has shown preliminary but promising results
for mindfulness-based interventions to benefit people with dementia and
caregivers. The aim of this review is (a) to provide a rationale for the
application of mindfulness in the context of dementia care by giving an overview
of studies on mindfulness for people with dementia and/or their caregivers and
(b) to provide suggestions for future projects on mindfulness in the context of
dementia and to give recommendations for future research.
PMID- 29951028
TI - Topological Reorganization of the Default Mode Network in Severe Male Obstructive
Sleep Apnea.
AB - Impaired spontaneous regional activity and altered topology of the brain network
have been observed in obstructive sleep apnea (OSA). However, the mechanisms of
disrupted functional connectivity (FC) and topological reorganization of the
default mode network (DMN) in patients with OSA remain largely unknown. We
explored whether the FC is altered within the DMN and examined topological
changes occur in the DMN in patients with OSA using a graph theory analysis of
resting-state functional magnetic resonance imaging data and evaluated the
relationship between neuroimaging measures and clinical variables. Resting-state
data were obtained from 46 male patients with untreated severe OSA and 46 male
good sleepers (GSs). We specifically selected 20 DMN subregions to construct the
DMN architecture. The disrupted FC and topological properties of the DMN in
patients with OSA were characterized using graph theory. The OSA group showed
significantly decreased FC of the anterior-posterior DMN and within the posterior
DMN, and also showed increased FC within the DMN. The DMN exhibited small-world
topology in both OSA and GS groups. Compared to GSs, patients with OSA showed a
decreased clustering coefficient (Cp) and local efficiency, and decreased nodal
centralities in the left posterior cingulate cortex and dorsal medial prefrontal
cortex, and increased nodal centralities in the ventral medial prefrontal cortex
and the right parahippocampal cortex. Finally, the abnormal DMN FC was
significantly related to Cp, path length, global efficiency, and Montreal
cognitive assessment score. OSA showed disrupted FC within the DMN, which may
have contributed to the observed topological reorganization. These findings may
provide further evidence of cognitive deficits in patients with OSA.
PMID- 29951029
TI - Osteoarthritis Increases Paresthestic and Akathisic Pain, Anxiety Case-ness, and
Depression Severity in Patients With Parkinson's Disease.
AB - Objective: Parkinson's disease (PD) patients are known to suffer from pain,
anxiety, and depression, but the exact degree of association between the two is
unknown. As many PD patients also suffer from physical impairments, this cross
sectional case-control study sets out to compare and determine the case-ness of
pain, anxiety and depression in PD patients that suffer with or without
symptomatic osteoarthritis (OA). The goal of this study, therefore, was to
observe if additional pain associated with comorbid OA in PD patients is
correlated with greater depression and anxiety rates. The importance of
understanding the burden of pain and increased depression severity of PD and OA
patients is so that they may be screened appropriately based on the symptoms,
which may increase their overall quality of life. Methods:This cross-sectional
case-control study included 3 groups of 34 patients and 78 healthy age and gender
matched control participants. PD patients with symptomatic OA (PD+OA), PD
patients without symptomatic OA (PD), patients with symptomatic OA but no PD
(OA), and healthy control participants (Control). A PD patient group with
Restless Legs Syndrome (PD+RLS) of 27 patients was also included. All
participants completed questionnaires to assess for pain, depression, and
anxiety. Results:PD+OA and PD patients had worsened depression severity and were
more likely to report anxiety and depression case-ness than OA patients. PD+OA
patients were more likely to complain about paresthestic and akasthisic pain, but
less likely to complain about aching pain compared to PD patients and OA
patients. PD+OA patients were more likely to have greater pain severity, and were
more likely to report radiating and sharp pain than PD+RLS patients. PD+OA
patients were also more likely to report higher depression case-ness than PD+RLS
patients. Conclusion:PD with OA seems to be linked with specific pain
characteristics (akathisia and paraesthesia) as well as heightened overall pain
severity and pain interference in comparison to OA alone, PD alone and PD with
RLS. PD is also correlated with depression severity and anxiety case-ness in OA
when compared to the OA alone, PD alone and PD with RLS.
PMID- 29951030
TI - Transplantation of Neural Precursor Cells Attenuates Chronic Immune Environment
in Cervical Spinal Cord Injury.
AB - Inflammation after traumatic spinal cord injury (SCI) is non-resolving and thus
still present in chronic injury stages. It plays a key role in the
pathophysiology of SCI and has been associated with further neurodegeneration and
development of neuropathic pain. Neural precursor cells (NPCs) have been shown to
reduce the acute and sub-acute inflammatory response after SCI. In the present
study, we examined effects of NPC transplantation on the immune environment in
chronic stages of SCI. SCI was induced in rats by clip-compression of the
cervical spinal cord at the level C6-C7. NPCs were transplanted 10 days post
injury. The functional outcome was assessed weekly for 8 weeks using the Basso,
Beattie, and Bresnahan scale, the CatWalk system, and the grid walk test.
Afterwards, the rats were sacrificed, and spinal cord sections were examined for
M1/M2 macrophages, T lymphocytes, astrogliosis, and apoptosis using
immunofluorescence staining. Rats treated with NPCs had compared to the control
group significantly fewer pro-inflammatory M1 macrophages and reduced
immunodensity for inducible nitric oxide synthase (iNOS), their marker enzyme.
Anti-inflammatory M2 macrophages were rarely present 8 weeks after the SCI. In
this model, the sub-acute transplantation of NPCs did not support survival and
proliferation of M2 macrophages. Post-traumatic apoptosis, however, was
significantly reduced in the NPC group, which might be explained by the altered
microenvironment following NPC transplantation. Corresponding to these findings,
reactive astrogliosis was significantly reduced in NPC-transplanted animals.
Furthermore, we could observe a trend toward smaller cavity sizes and functional
improvement following NPC transplantation. Our data suggest that transplantation
of NPCs following SCI might attenuate inflammation even in chronic injury stages.
This might prevent further neurodegeneration and could also set a stage for
improved neuroregeneration after SCI.
PMID- 29951031
TI - Evaluation of Clinical and Paraclinical Findings for the Differential Diagnosis
of Autoimmune and Infectious Encephalitis.
AB - Background: The differential diagnosis of autoimmune and infectious encephalitis
is notoriously difficult. For this study, we compare the presenting clinical
symptoms and paraclinical test results of autoimmune and infectious encephalitis
patients. A clinical algorithm for the diagnosis of autoimmune encephalitis has
recently been published. We test these Graus criteria on our cohort for
diagnostic sensitivity and specificity within the first week of presentation.
Methods: We included all patients seen at our department within a 10-year-period
who were diagnosed with encephalitis. The discharge diagnoses served as the
reference standard for testing the clinical algorithm for two conditions: use of
all the clinical information available on a patient during the first week of
hospital admission assuming undefined autoantibody status and microbiological
test results (C1) vs. consideration of all the information available on a
patient, including the results of serological and microbiological testing (C2).
Results: Eighty-four patients (33 autoimmune, 51 infectious encephalitis) were
included in the study. Fifty-one (17 autoimmune, 34 infectious) had a definite
clinical diagnosis. The two groups differed significantly for the presence of
headache, fever, epileptic seizures, and CSF cell-count at presentation.
Application of the clinical algorithm resulted in a low sensitivity (58%) and
very low specificity (8%) for the diagnosis of possible autoimmune encephalitis.
The latter increased considerably in the subgroups of probable and definite
autoimmune encephalitis. Whereas the sensitivity of the individual diagnostic
categories was clearly time-dependent, the specificity rested foremost on the
knowledge of the results of microbiological testing. Anti-CASPR2- and -LGI1
associated autoimmune encephalitis and tick-borne virus encephalitis presented
particular diagnostic pitfalls. Conclusions: We define clinical symptoms and
paraclinical test results which prove valuable for the differentiation between
infectious and autoimmune encephalitis. Sensitivity and specificity of the
clinical algorithm clearly depended on the amount of time passed after hospital
admission and knowledge of microbiological test results. Accepting this
limitation for the acute setting, the algorithm remains a valuable diagnostic aid
for antibody-negative autoimmune encephalitis or in resource-poor settings. The
initiation of immune therapy however should not be delayed if an autoimmune
etiology is considered likely, even if the diagnostic criteria of the algorithm
are not (yet) fulfilled.
PMID- 29951032
TI - Rating Scales for Movement Disorders With Sleep Disturbances: A Narrative Review.
AB - Introduction: In recent years, a wide variety of rating scales and questionnaires
for movement disorders have been developed and published, making reviews on their
contents, and attributes convenient for the potential users. Sleep disorders are
frequently present in movement disorders, and some movement disorders are
accompanied by specific sleep difficulties. Aim: The aim of this study is to
perform a narrative review of the most frequently used rating scales for movement
disorders with sleep problems, with special attention to those recommended by the
International Parkinson and Movement Disorders Society. Methods: Online databases
(PubMed, SCOPUS, Web of Science, Google Scholar), related references from papers
and websites and personal files were searched for information on comprehensive or
global rating scales which assessed sleep disturbances in the following movement
disorders: akathisia, chorea, dystonia, essential tremor, myoclonus, multiple
system atrophy, Parkinson's disease, progressive supranuclear palsy, and tics and
Tourette syndrome. For each rating scale, its objective and characteristics, as
well as a summary of its psychometric properties and recommendations of use are
described. Results: From 22 rating scales identified for the selected movement
disorders, only 5 included specific questions on sleep problems. Movement
Disorders Society-Unified Parkinson's Disease Rating scale (MDS-UPDRS), Non-Motor
Symptoms Scale and Questionnaire (NMSS and NMSQuest), Scales for Outcomes in
Parkinson's Disease (SCOPA)-Autonomic and Progressive Supranuclear Palsy Rating
Scale (PSPRS) were the only rating scales that included items for assessing sleep
disturbances. Conclusions: Despite sleep problems are frequent in movement
disorders, very few of the rating scales addresses these specific symptoms. This
may contribute to an infra diagnosis and mistreatment of the sleep problems in
patients with movement disorders.
PMID- 29951033
TI - Phantom Sensations Following Brachial Plexus Nerve Block: A Case Report.
AB - Following the administration of brachial plexus anesthesia for right thumb
carpometacarpal arthroplasty with ligament reconstruction, a 54-year-old woman
with all limbs intact developed phantom limb sensations, including the
misperception of the placement of her right arm and frozen limb sensations in her
fingers. Immobility of her fingers in a stacked position was experienced for ~3.5
days after surgery, and she described her phantom sensations as the hand
experiencing "tingling" and feeling "heavy." While the onset of these phantom
sensations occurred almost immediately after administration of brachial plexus
anesthesia, they lasted for ~69 h after anesthesia wear off, suggesting that
cortical effects from denervation resolves much more slowly than initial
remapping, giving insight into the mechanisms behind phantom limb sensations that
are often experienced by amputees.
PMID- 29951034
TI - Thyroid Function in Pregnant Women With Moderate to Severe Alcohol Consumption Is
Related to Infant Developmental Outcomes.
AB - Introduction: Fetal alcohol spectrum disorders (FASD) have an estimated global
prevalence of 2-5% of births, but prevalence is reported to be as high as 15.5%
for FASD in certain high-risk communities in South Africa. Preclinical studies
demonstrate that alcohol consumption during pregnancy interferes with thyroid
hormone availability and function and negatively impacts exposed offspring. Very
little is currently reported on this phenomenon in humans. Methods: This pilot
study was embedded in the Drakenstein Child Health Study, a multi-disciplinary
longitudinal birth cohort study investigating the early biological and
psychosocial determinants of child health in South Africa. Twenty one mothers and
their children with moderate-severe prenatal alcohol exposure (PAE) and 19
mothers and their children with no alcohol exposure were investigated. Maternal
exposure history and blood samples were collected in mid-pregnancy and analyzed
for serum-free thyroxin (FT4), free triiodothyronine (FT3), and thyroid
stimulating hormone (TSH). Children were assessed with formally measured growth
parameters and development was evaluated using the Bayley III Scales of Infant
and Toddler Development (BSID III) at 6 and 24 months of age. Results: While
there were no significant differences in serum TSH and FT4 between groups, FT3
levels were significantly higher in mothers with moderate-severe prenatal alcohol
use. In abstinent pregnant women, levels of FT4 were significantly correlated
with infants' scores on cognitive measures at 6 and 24 months of age and with
levels of gross motor skills at 24 months. However, in mothers with alcohol use,
FT4 levels were not correlated with any cognitive or motor skills, but FT3 levels
were significantly associated with scores on children's social-emotional
development at 24 months of age. Discussion: Thyroid function in PAE is
sufficiently disrupted to lead to alterations in serum FT3 levels. The contrast
in findings between PAE and abstinent dyads in their association of maternal
thyroid function and infant development further suggests that such disruption is
present and may contribute to adverse neurodevelopment. Further work is needed to
determine the relationship between peripheral thyroid indices during pregnancy
and neurodevelopmental outcomes in the context of PAE.
PMID- 29951036
TI - Vitamin D Level and Activities of Daily Living in Octogenarians: Cross-Sectional
Study.
AB - Introduction: Despite the growing number of octogenarians, little is known about
their vitamin D status and activities of daily living (ADL) relations. Objective:
The aim of this study was to investigate peculiarities of vitamin D and ADL and
to assess their relations in octogenarians. Methods: A cross-sectional study was
performed at the National Osteoporosis Centre located in Vilnius, Lithuania.
Community-dwelling ambulatory persons aged >=80 years were included. Current
users of vitamin D supplements were excluded. Total 25 hydroxyvitamin D
concentration in serum was measured with Cobas E411. Functional status was
assessed by Katz ADL and the Lawton Instrumental Activities of Daily Living
(IADL) scales. Subjects were divided into three groups according to age and into
two groups according to vitamin D level. One-way analysis of variance with post
hoc test was used to determine between-group comparisons. Associations between
vitamin D and ADL score, and IADL score were assessed using Spearman's
correlation. Results: The study was performed on 153 octogenarians: 81 (52.9%)
women and 72 (47.1%) men. The average age of subjects was 83.9 +/- 3.2 years.
Mean total 25 hydroxyvitamin D concentration was 11.2 +/- 7.0 ng/ml; 137 (89.5%)
persons had vitamin D deficiency, 12 (7.8%) had insufficiency, and only 4 (2.6%)
persons were vitamin D sufficient. Positive weak correlation between total 25
hydroxyvitamin D and ADL score (r = 0.2, p = 0.01) and very weak correlation
between total 25 hydroxyvitamin D and IADL score (r = 0.19, p = 0.02) were found.
Total 25 hydroxyvitamin D level was correlated with ADL score in women (r = 0.23,
p = 0.04). In the 80-84 years group ADL score correlated with total 25
hydroxyvitamin D level (r = 0.23, p = 0.02). Conclusion: The majority of
investigated octogenarians had vitamin D deficiency. The level of vitamin D was
associated with the ADL score. There was no association between the vitamin D
level and the IADL score, although a weak correlation was found between vitamin D
level and category of food preparation.
PMID- 29951035
TI - Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter
Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects.
AB - Background/objectives: The pathologic relationship linking obesity and lipid
dismetabolism with earlier onset of aging-related disorders, including
cardiovascular disease (CVD) and type-2 diabetes (T2D), is not fully elucidate.
Chronic inflammatory state, in obese individuals, may accelerate cellular aging.
However, leukocyte telomere length (LTL), the cellular biological aging
indicator, is elusively linked with obesity. Recent studies indicate that sterol
27-hydroxylase (CYP27A1) is an emerging antiatherogenic enzyme, that, by
converting extrahepatic cholesterol to 27-hydroxycholesterol, facilitates
cholesterol removal via high-density lipoprotein-cholesterol (HDL-C). We tested
the hypothesis that obese subjects who carry at least three copies of CYP27A1 low
hydroxylation (LH) activity genome-wide-validated alleles (rs4674345A,
rs1554622A, and rs4674338G) present premature aging, as reflected in shorter LTL
and higher levels of CVD/T2D risk factors, including reduced HDL-C.
Subjects/methods: Obese subjects from SPHERE project {n = 1,457; overweight [body
mass index (BMI) 25-30 kg/m2] 65.8% and severe-obese (BMI > 30 kg/m2) 34.2%} were
characterized for the presence from 0 to 6 LH-CYP27A1 allele copy number.
Univariate and multivariable sex-age-smoking-adjusted linear-regression models
were performed to compare CVD/T2D risk factors and biological aging (LTL) in
relation to the combined BMI-LH groups: overweight-LH: 0-2, overweight-LH: 3-6,
severe-obese-LH: 0-2, and severe-obese-LH: 3-6. Results: Higher LTL attrition was
found in severe-obese than overweight individuals (p < 0.001). Multivariable
model reveals that among severe-obese patients those with LH: 3-6 present higher
LTL attrition than LH: 0-2 (p < 0.05). Univariate and multivariable models
remarkably show that insulin resistance is higher both in overweight-LH: 3-6 vs
overweight-LH: 0-2 (p < 0.001) and in severe-obese-LH: 3-6 vs severe-obese-LH: 0
2 (p < 0.0001), and HDL-C is lower in overweight-LH: 3-6 than overweight-LH: 0-2
(p < 0.05 and p < 001). Finally, most of the well-known (i.e., blood pressure,
heart rate, waist to hip, triglycerides, and HDL-C) and novel CVD risk factors
[i.e., inflammation markers (C-reactive protein, leukocytes, and chemoattractant
protein-1), fibrinogen, and glucose homeostasis (i.e., insulin resistance, and
glycated hemoglobin)] are substantially (p < 0.0001) altered in severe-obese-LH:
0-2 vs overweight-LH: 0-2, pointing to the fact that obesity leads to worsen the
CVD/T2D risk factor profile. Conclusion: Our study supports evidence that CYP27A1
genetic characterization identifies persons at higher risk to develop CVD and
T2D, on which better converge preventive measures, and opens new perspectives on
mechanisms that link obesity with aging-related disorders.
PMID- 29951037
TI - Exacting Responses: Lack of Endocrine Cephalic Phase Responses Upon Oro-Sensory
Exposure.
AB - Oro-sensory exposure (OSE) to food plays an important role in the regulation of
food intake. One proposed underlying mechanism is the occurrence of cephalic
phase responses (CPRs). CPRs include the pre-digestive endocrine responses
induced by food-related sensory input. Yet, whether OSE duration or sweetness
intensity affects CPRs is unknown. The objective of this study was to determine
the independent and interactive effects of oro-sensory duration (chewing) and
stimulation intensity (sweetness) on endocrine CPRs and satiation. Eighteen males
(22 +/- 2 years, BMI 22 +/- 2 kg/m2) participated in a 2 * 2 randomized study
with a control condition. Each session participants performed modified sham
feeding (MSF) with one of the four gel-based model foods. During the control
session no MSF was performed. Model foods differed in chewing duration (hard or
soft texture) and sweetness (low or high intensity). During each session, eight
blood samples were collected up till 25 min after MSF onset. Subsequently, food
intake from an ad libitum lunch was measured. No typical CPR was found for
insulin, pancreatic polypeptide (PP), and ghrelin. However, the overall PP
response was 1.1 times greater for the hard sweet MSF condition compared to
control (p = 0.02). Overall ghrelin responses were 1.1 times greater for the hard
model food compared to the soft model food conditions (p = 0.003). These
differences in endocrine response were not associated with differences in food
intake at the subsequent meal. Exploratory sub-analysis of the responsive insulin
curves showed that after 2.5 min of MSF the hard texture model foods insulin
concentrations were 1.2 greater compared to the soft texture. These findings
indicate that texture hardness and sweetness increase the overall PP response and
that MSF on hard texture increases the overall ghrelin response compared to soft
texture model foods. However, MSF on model foods does not lead to a typical CPR.
This study, among others, shows that there are major dissimilarities in the
endocrine responses to food stimulation between individuals. This emphasizes the
importance of considering cephalic responders and non-responders. More research
is needed to understand CPRs in relation to food texture and taste properties.
PMID- 29951038
TI - Fungal Gene Mutation Analysis Elucidating Photoselective Enhancement of UV-C
Disinfection Efficiency Toward Spoilage Agents on Fruit Surface.
AB - Short-wave ultraviolet (UV-C) treatment represents a potent, clean and safe
substitute to chemical sanitizers for fresh fruit preservation. However, the
dosage requirement for microbial disinfection may have negative effects on fruit
quality. In this study, UV-C was found to be more efficient in killing spores of
Botrytis cinerea in dark and red light conditions when compared to white and blue
light. Loss of the blue light receptor gene Bcwcl1, a homolog of wc-1 in
Neurospora crassa, led to hypersensitivity to UV-C in all light conditions
tested. The expression of Bcuve1 and Bcphr1, which encode UV-damage endonuclease
and photolyase, respectively, were strongly induced by white and blue light in a
Bcwcl1-dependent manner. Gene mutation analyses of Bcuve1 and Bcphr1 indicated
that they synergistically contribute to survival after UV-C treatment. In vivo
assays showed that UV-C (1.0 kJ/m2) abolished decay in drop-inoculated fruit only
if the UV-C treatment was followed by a dark period or red light, while in
contrast, typical decay appeared on UV-C irradiated fruits exposed to white or
blue light. In summary, blue light enhances UV-C resistance in B. cinerea by
inducing expression of the UV damage repair-related enzymes, while the efficiency
of UV-C application for fruit surface disinfection can be enhanced in dark or red
light conditions; these principles seem to be well conserved among postharvest
fungal pathogens.
PMID- 29951039
TI - Microbiomes of North American Triatominae: The Grounds for Chagas Disease
Epidemiology.
AB - Insect microbiomes influence many fundamental host traits, including functions of
practical significance such as their capacity as vectors to transmit parasites
and pathogens. The knowledge on the diversity and development of the gut
microbiomes in various blood feeding insects is thus crucial not only for
theoretical purposes, but also for the development of better disease control
strategies. In Triatominae (Heteroptera: Reduviidae), the blood feeding vectors
of Chagas disease in South America and parts of North America, the investigation
of the microbiomes is in its infancy. The few studies done on microbiomes of
South American Triatominae species indicate a relatively low taxonomic diversity
and a high host specificity. We designed a comparative survey to serve several
purposes: (I) to obtain a better insight into the overall microbiome diversity in
different species, (II) to check the long term stability of the interspecific
differences, (III) to describe the ontogenetic changes of the microbiome, and
(IV) to determine the potential correlation between microbiome composition and
presence of Trypanosoma cruzi, the causative agent of Chagas disease. Using 16S
amplicons of two abundant species from the southern US, and four laboratory
reared colonies, we showed that the microbiome composition is determined by host
species, rather than locality or environment. The OTUs (Operational Taxonomic
Units) determination confirms a low microbiome diversity, with 12-17 main OTUs
detected in wild populations of T. sanguisuga and T. protracta. Among the
dominant bacterial taxa are Acinetobacter and Proteiniphilum but also the
symbiotic bacterium Arsenophonus triatominarum, previously believed to only live
intracellularly. The possibility of ontogenetic microbiome changes was evaluated
in all six developmental stages and feces of the laboratory reared model Rhodnius
prolixus. We detected considerable changes along the host's ontogeny, including
clear trends in the abundance variation of the three dominant bacteria, namely
Enterococcus, Acinetobacter, and Arsenophonus. Finally, we screened the samples
for the presence of Trypanosoma cruzi. Comparing the parasite presence with the
microbiome composition, we assessed the possible significance of the latter in
the epidemiology of the disease. Particularly, we found a trend toward more
diverse microbiomes in Trypanosoma cruzi positive T. protracta specimens.
PMID- 29951041
TI - Transmission Dynamics of Hyper-Endemic Multi-Drug Resistant Klebsiella pneumoniae
in a Southeast Asian Neonatal Unit: A Longitudinal Study With Whole Genome
Sequencing.
AB - Background:Klebsiella pneumoniae is an important and increasing cause of life
threatening disease in hospitalized neonates. Third generation cephalosporin
resistance (3GC-R) is frequently a marker of multi-drug resistance, and can
complicate management of infections. 3GC-R K. pneumoniae is hyper-endemic in many
developing country settings, but its epidemiology is poorly understood and
prospective studies of endemic transmission are lacking. We aimed to determine
the transmission dynamics of 3GC-R K. pneumoniae in a newly opened neonatal unit
(NU) in Cambodia and to address the following questions: what is the diversity of
3GC-R K. pneumoniae both within- and between-host; to what extent is high
carriage prevalence driven by ward-based transmission; and to what extent can
environmental contamination explain patterns of patient acquisition. Methods: We
performed a prospective longitudinal study between September and November 2013.
Rectal swabs from consented patients were collected upon NU admission and every 3
days thereafter. Morphologically different colonies from swabs growing
cefpodoxime-resistant K. pneumoniae were selected for whole-genome sequencing
(WGS). Results: One hundred and fifty-eight samples from 37 patients and 7
environmental sites were collected. 32/37 (86%) patients screened positive for
3GC-R K. pneumoniae and 93 colonies from 119 swabs were successfully sequenced.
Isolates were resistant to a median of six (range 3-9) antimicrobials. WGS
revealed high diversity; pairwise distances between isolates from the same
patient were either 0-1 SNV or >1,000 SNVs; 19/32 colonized patients harbored K.
pneumoniae colonies differing by >1000 SNVs. Diverse lineages accounted for 18
probable importations to the NU and nine probable transmission clusters involving
19/37 (51%) of screened patients. Median cluster size was five patients (range 3
9). Seven out of 46 environmental swabs (15%) were positive for 3GC-R K.
pneumoniae. Environmental sources were plausible sources for acquisitions in 2/9
transmission clusters, though in both cases other patients were also plausible
sources. Conclusion: The epidemiology of 3GC-R K. pneumoniae was characterized by
multiple introductions, high within- and between host diversity and a dense
network of cross-infection, with half of screened neonates part of a transmission
cluster. We found no evidence to suggest that environmental contamination was
playing a dominant role in transmission.
PMID- 29951040
TI - Description and Comparative Genomics of Macrococcus caseolyticus subsp. hominis
subsp. nov., Macrococcus goetzii sp. nov., Macrococcus epidermidis sp. nov., and
Macrococcus bohemicus sp. nov., Novel Macrococci From Human Clinical Material
With Virulence Potential and Suspected Uptake of Foreign DNA by Natural
Transformation.
AB - The genus Macrococcus is a close relative of the genus Staphylococcus. Whilst
staphylococci are widespread as human pathogens, macrococci have not yet been
reported from human clinical specimens. Here we investigated Gram-positive and
catalase-positive cocci recovered from human clinical material and identified as
Macrococcus sp. by a polyphasic taxonomic approach and by comparative genomics.
Relevant phenotypic, genotypic and chemotaxonomic methods divided the analyzed
strains into two separate clusters within the genus Macrococcus. Comparative
genomics of four representative strains revealed enormous genome structural
plasticity among the studied isolates. We hypothesize that high genomic
variability is due to the presence of a com operon, which plays a key role in the
natural transformation of bacilli and streptococci. The possible uptake of
exogenous DNA by macrococci can contribute to a different mechanism of evolution
from staphylococci, where phage-mediated horizontal gene transfer predominates.
The described macrococcal genomes harbor novel plasmids, genomic islands and
islets, as well as prophages. Capsule gene clusters, intracellular protease, and
a fibronectin-binding protein enabling opportunistic pathogenesis were found in
all four strains. Furthermore, the presence of a CRISPR-Cas system with 90
spacers in one of the sequenced genomes corresponds with the need to limit the
burden of foreign DNA. The highly dynamic genomes could serve as a platform for
the exchange of virulence and resistance factors, as was described for the
methicillin resistance gene, which was found on the novel composite SCCmec-like
element containing a unique mec gene complex that is considered to be one of the
missing links in SCC evolution. The phenotypic, genotypic, chemotaxonomic and
genomic results demonstrated that the analyzed strains represent one novel
subspecies and three novel species of the genus Macrococcus, for which the names
Macrococcus caseolyticus subsp. hominis subsp. nov. (type strain CCM 7927T = DSM
103682T), Macrococcus goetzii sp. nov. (type strain CCM 4927T = DSM 103683T),
Macrococcus epidermidis sp. nov. (type strain CCM 7099T = DSM 103681T), and
Macrococcus bohemicus sp. nov. (type strain CCM 7100T = DSM 103680T) are
proposed. Moreover, a formal description of Macrococcus caseolyticus subsp.
caseolyticus subsp. nov. and an emended description of the genus Macrococcus are
provided.
PMID- 29951042
TI - Pneumococcal LytR Protein Is Required for the Surface Attachment of Both Capsular
Polysaccharide and Teichoic Acids: Essential for Pneumococcal Virulence.
AB - The LytR-Cps-Psr family proteins are commonly present in Gram-positive bacteria,
which have been shown to implicate in anchoring cell wall-related glycopolymers
to the peptidoglycan. Here, we report the cellular function of SPD_1741 (LytR) in
Streptococcus pneumoniae and its role in virulence of pneumococci. Pneumococcal
DeltalytR mutants have been successfully constructed by replacing the lytR gene
with erm cassette. The role of LytR in pneumococcal growth was determined by
growth experiments, and surface accessibility of the LytR protein was analyzed
using flow cytometry. Transmission electron microscopy (TEM) and immunoblotting
were used to reveal the changes in capsular polysaccharide (CPS). Dot blot and
ELISA were used to quantify the amount of teichoic acids (TAs). The contribution
of LytR on bacterial virulence was assessed using in vitro phagocytosis assays
and infection experiments. Compared to the wild-type strain, the DeltalytR mutant
showed a defect in growth which merely grew to a maximal OD620 of 0.2 in the
liquid medium. The growth of the DeltalytR mutant could be restored by addition
of recombinant DeltaTM-LytR protein in culture medium in a dose-dependent manner.
TEM results showed that the D39DeltalytR mutant was impaired in the surface
attachment of CPS. Deletion of lytR gene also impaired the retention of TAs on
the surface of pneumococci. The reduction of CPS and TAs on the pneumocccal cells
were confirmed using Dot blot and ELISA assays. Compared to wild-type D39, the
DeltalytR mutant was more susceptible to the phagocytosis. Animal studies showed
that the ability to colonize the nasophaynx and virulence of pneumococci were
affected by impairment of the lytR gene. Collectively, these results suggest that
pneumococcal LytR is involved in anchoring both the CPS and TAs to cell wall,
which is important for virulence of pneumococci.
PMID- 29951043
TI - Growth and Product Formation of Clostridium ljungdahlii in Presence of Cyanide.
AB - Cyanide is a minor constituent of crude syngas whose content depends on the
feedstock and gasification procedure. It is a known poison to metal catalysts and
inhibits iron-containing enzymes like carbon monoxide dehydrogenase of acetogenic
organisms. Therefore, it is considered a component that has to be removed from
the gas stream prior to use in chemical synthesis or syngas fermentation. We show
that the growth rate and maximum biomass concentration of Clostridium ljungdahlii
are unaffected by cyanide at concentrations of up to 1.0 mM with fructose as a
carbon source and up to 0.1 mM with syngas as a carbon source. After the culture
is adapted to cyanide it shows no growth inhibition. While the difference in
growth is an increasing lag-phase with increasing cyanide concentrations, the
product spectrum shifts from 97% acetic acid and 3% ethanol at 0 mM cyanide to
20% acetic acid and 80% ethanol at 1.0 mM cyanide for cultures growing on
(fructose) and 80% acetic acid and 20% ethanol at 0.1 mM cyanide (syngas).
PMID- 29951044
TI - A Preclinical Model for the ATLL Lymphoma Subtype With Insights Into the Role of
Microenvironment in HTLV-1-Mediated Lymphomagenesis.
AB - Adult T cell Leukemia/Lymphoma (ATLL) is a mature T cell malignancy associated
with Human T cell Leukemia Virus type 1 (HTLV-1) infection. Among its four main
clinical subtypes, the prognosis of acute and lymphoma variants remains poor. The
long latency (3-6 decades) and low incidence (3-5%) of ATLL imply the involvement
of viral and host factors in full-blown malignancy. Despite multiple preclinical
and clinical studies, the contribution of the stromal microenvironment in ATLL
development is not yet completely unraveled. The aims of this study were to
investigate the role of the host microenvironment, and specifically fibroblasts,
in ATLL pathogenesis and to propose a murine model for the lymphoma subtype. Here
we present evidence that the oncogenic capacity of HTLV-1-immortalized C91/PL
cells is enhanced when they are xenotransplanted together with human foreskin
fibroblasts (HFF) in immunocompromised BALB/c Rag2-/-gammac-/- mice. Moreover,
cell lines derived from a developed lymphoma and their subsequent in vivo
passages acquired the stable property to induce aggressive T cell lymphomas. In
particular, one of these cell lines, C91/III cells, consistently induced
aggressive lymphomas also in NOD/SCID/IL2Rgammac KO (NSG) mice. To dissect the
mechanisms linked to this enhanced tumorigenic ability, we quantified 45 soluble
factors released by these cell lines and found that 21 of them, mainly pro
inflammatory cytokines and chemokines, were significantly increased in C91/III
cells compared to the parental C91/PL cells. Moreover, many of the increased
factors were also released by human fibroblasts and belonged to the known
secretory pattern of ATLL cells. C91/PL cells co-cultured with HFF showed
features reminiscent of those observed in C91/III cells, including a similar
secretory pattern and a more aggressive behavior in vivo. On the whole, our data
provide evidence that fibroblasts, one of the major stromal components, might
enhance tumorigenesis of HTLV-1-infected and immortalized T cells, thus throwing
light on the role of microenvironment contribution in ATLL pathogenesis. We also
propose that the lymphoma induced in NSG mice by injection with C91/III cells
represents a new murine preclinical ATLL model that could be adopted to test
novel therapeutic interventions for the aggressive lymphoma subtype.
PMID- 29951045
TI - Molecular Epidemiology of mcr-Encoded Colistin Resistance in Enterobacteriaceae
From Food-Producing Animals in Italy Revealed Through the EU Harmonized
Antimicrobial Resistance Monitoring.
AB - Colistin resistance by mobilisable mcr genes has been described in bacteria of
food-animal origin worldwide, which has raised public health concerns about its
potential foodborne transmission to human pathogenic bacteria. Here we provide
baseline information on the molecular epidemiology of colistin-resistant, mcr
positive Escherichia coli and Salmonella isolates in food-producing animals in
Italy in 2014-2015. A total 678, 861 and 236 indicator E. coli, Extended Spectrum
Beta-Lactamase (ESBL)/AmpC-producing E. coli, and Salmonella isolates,
respectively, were tested for colistin susceptibility. These isolates were
collected according to the EU harmonized antimicrobial resistance monitoring
program and are representative of at least 90 and 80% of the Italian poultry
(broiler chickens and turkeys) and livestock (pigs and bovines < 12 months)
production, respectively. Whole genome sequencing by Illumina technology and
bioinformatics (Center for Genomic Epidemiology pipeline) were used to type 42
mcr-positive isolates by PCR. Colistin resistance was mainly observed in the
ESBL/AmpC E. coli population, and was present in 25.9, 5.3, 6.5, and 3.9% of such
isolates in turkeys, broilers, pigs, and bovines, respectively. Most colistin
resistant isolates (141/161, 87.5%) harbored genes of the mcr-1 group. mcr-1 was
also detected in a small proportion of Salmonella isolates (3/146, 2.0%) in
turkeys. Additional mcr types were mcr-3 in four ESBL-producing E. coli from
bovines, and two mcr-4 in ESBL (n = 1) and indicator E. coli (n = 1) from pigs
and bovines. We describe notable diversity of mcr variants with predominance of
mcr-1.1 and mcr-1.2 on conjugative IncX4 plasmids in E. coli and in Salmonella
serovars Typhimurium, Newport, Blockley from turkey. A new variant, mcr-1.13 was
detected in the chromosome in E. coli in turkey and pig isolates. Additionally,
we describe mcr-3.2 and mcr-4.3 in E. coli from bovines, and mcr-4.2 in E. coli
from pigs. These findings elucidate the epidemiology of colistin resistance in
food-producing animals in Italy along with its genetic background, and highlight
the likelihood of mcr horizontal transfer between commensal bacteria and major
food-borne pathogens (Salmonella) within the same type of productions. Thorough
action and strategies are needed in order to mitigate the risk of mcr transfer to
humans, in a "One Health" perspective.
PMID- 29951046
TI - Viral Communities of Shark Bay Modern Stromatolites.
AB - Single stranded DNA viruses have been previously shown to populate the oceans on
a global scale, and are endemic in microbialites of both marine and freshwater
systems. We undertook for the first time direct viral metagenomic shotgun
sequencing to explore the diversity of viruses in the modern stromatolites of
Shark Bay Australia. The data indicate that Shark Bay marine stromatolites have
similar diversity of ssDNA viruses to that of Highbourne Cay, Bahamas. ssDNA
viruses in cluster uniquely in Shark Bay and Highbourne Cay, potentially due to
enrichment by phi29-mediated amplification bias. Further, pyrosequencing data was
assembled from the Shark Bay systems into two putative viral genomes that are
related to Genomoviridae family of ssDNA viruses. In addition, the cellular
fraction was shown to be enriched for antiviral defense genes including CRISPR
Cas, BREX (bacteriophage exclusion), and DISARM (defense island system associated
with restriction-modification), a potentially novel finding for these systems.
This is the first evidence for viruses in the Shark Bay stromatolites, and these
viruses may play key roles in modulating microbial diversity as well as
potentially impacting ecosystem function through infection and the recycling of
key nutrients.
PMID- 29951047
TI - History and Status of Selected Hosts of the Ralstonia solanacearum Species
Complex Causing Bacterial Wilt in Brazil.
AB - Bacterial wilt induced by the Ralstonia solanacearum species complex is endemic
to Brazil, where it can cause variable losses in many hosts. Its economic
importance, however, cannot be precisely measured due to Brazil's continental
size, subject to variable weather conditions which directly affect disease
expression. The objectives of this paper were (i) to gather scattered information
on historical facts; (ii) to show the current distribution of the pathogen in the
country, and (iii) to comment on future trends on the importance of the disease
in economically important current and potential hosts, based on the pathogen's
variability and the global climate change under way.
PMID- 29951048
TI - Sediment Microbial Communities Influenced by Cool Hydrothermal Fluid Migration.
AB - Cool hydrothermal systems (CHSs) are prevalent across the seafloor and discharge
fluid volumes that rival oceanic input from rivers, yet the microbial ecology of
these systems are poorly constrained. The Dorado Outcrop on the ridge flank of
the Cocos Plate in the northeastern tropical Pacific Ocean is the first confirmed
CHS, discharging minimally altered <15 degrees C fluid from the shallow
lithosphere through diffuse venting and seepage. In this paper, we characterize
the resident sediment microbial communities influenced by cool hydrothermal
advection, which is evident from nitrate and oxygen concentrations. 16S rRNA gene
sequencing revealed that Thaumarchaea, Proteobacteria, and Planctomycetes were
the most abundant phyla in all sediments across the system regardless of
influence from seepage. Members of the Thaumarchaeota (Marine Group I),
Alphaproteobacteria (Rhodospirillales), Nitrospirae, Nitrospina, Acidobacteria,
and Gemmatimonadetes were enriched in the sediments influenced by CHS advection.
Of the various geochemical parameters investigated, nitrate concentrations
correlated best with microbial community structure, indicating structuring based
on seepage of nitrate-rich fluids. A comparison of microbial communities from
hydrothermal sediments, seafloor basalts, and local seawater at Dorado Outcrop
showed differences that highlight the distinct niche space in CHS. Sediment
microbial communities from Dorado Outcrop differ from those at previously
characterized, warmer CHS sediment, but are similar to deep-sea sediment habitats
with surficial ferromanganese nodules, such as the Clarion Clipperton Zone. We
conclude that cool hydrothermal venting at seafloor outcrops can alter the local
sedimentary oxidation-reduction pathways, which in turn influences the microbial
communities within the fluid discharge affected sediment.
PMID- 29951049
TI - Label-Free Quantitative Proteomics Identifies Novel Plasma Biomarkers for
Distinguishing Pulmonary Tuberculosis and Latent Infection.
AB - The lack of effective differential diagnostic methods for active tuberculosis
(TB) and latent infection (LTBI) is still an obstacle for TB control.
Furthermore, the molecular mechanism behind the progression from LTBI to active
TB has been not elucidated. Therefore, we performed label-free quantitative
proteomics to identify plasma biomarkers for discriminating pulmonary TB (PTB)
from LTBI. A total of 31 overlapping proteins with significant difference in
expression level were identified in PTB patients (n = 15), compared with LTBI
individuals (n = 15) and healthy controls (HCs, n = 15). Eight differentially
expressed proteins were verified using western blot analysis, which was 100%
consistent with the proteomics results. Statistically significant differences of
six proteins were further validated in the PTB group compared with the LTBI and
HC groups in the training set (n = 240), using ELISA. Classification and
regression tree (CART) analysis was employed to determine the ideal protein
combination for discriminating PTB from LTBI and HC. A diagnostic model
consisting of alpha-1-antichymotrypsin (ACT), alpha-1-acid glycoprotein 1 (AGP1),
and E-cadherin (CDH1) was established and presented a sensitivity of 81.2%
(69/85) and a specificity of 95.2% (80/84) in discriminating PTB from LTBI, and a
sensitivity of 81.2% (69/85) and a specificity of 90.1% (64/81) in discriminating
PTB from HCs. Additional validation was performed by evaluating the diagnostic
model in blind testing set (n = 113), which yielded a sensitivity of 75.0%
(21/28) and specificity of 96.1% (25/26) in PTB vs. LTBI, 75.0% (21/28) and 92.3%
(24/26) in PTB vs. HCs, and 75.0% (21/28) and 81.8% (27/33) in PTB vs. lung
cancer (LC), respectively. This study obtained the plasma proteomic profiles of
different M.TB infection statuses, which contribute to a better understanding of
the pathogenesis involved in the transition from latent infection to TB
activation and provide new potential diagnostic biomarkers for distinguishing PTB
and LTBI.
PMID- 29951050
TI - 5-Aminosalicylic Acid Alters the Gut Bacterial Microbiota in Patients With
Ulcerative Colitis.
AB - Background: The aim of this study was to clarify the effect of 5-aminosalicylic
acid (5-ASA) treatment on gut bacterial microbiota in patients with ulcerative
colitis (UC). Methods: A total of 57 UC patients, including 20 untreated and 37 5
ASA-treated, were recruited into an exploration cohort. We endoscopically
collected both non-inflamed and inflamed mucosal samples from all patients, and
compared the gut bacterial profiles using 16S rDNA sequencing. Ten untreated UC
patients were then treated with 5-ASA and subsequently recruited for an
independent validation study to confirm the acquired data. Results: In untreated
UC patients, compared with those in non-inflamed mucosae, Firmicutes (such as
Enterococcus) were decreased and Proteobacteria (e.g., Escherichia-Shigella) were
increased in the inflamed mucosae. Compared with the inflamed mucosae of
untreated UC patients, there was a higher abundance of Firmicutes (e.g.,
Enterococcus) and lower Proteobacteria (Escherichia-Shigella) in the inflamed
mucosae of 5-ASA treated UC patients. In the validation cohort, after
administration of 5-ASA, bacterial alteration was consistent with these data.
Furthermore, there was a skewed negative correlation between Escherichia-Shigella
and bacterial genera of Firmicutes in the inflamed mucosae. 5-ASA treatment
decreased the strength of bacterial correlation and weakened the skewed negative
correlation pattern. Conclusion: The microbial dysbiosis (mainly characterized by
an increased abundance in the Escherichia-Shigella genus) and the skewed negative
correlation between Escherichia-Shigella and bacterial genera of Firmicutes are
two characteristics of the inflamed mucosae of UC patients. 5-ASA treatment
decreases Escherichia-Shigella and weakens the skewed correlations, which may be
related to its treatment efficiency.
PMID- 29951051
TI - Storage-Induced Platelet Apoptosis Is a Potential Risk Factor for
Alloimmunization Upon Platelet Transfusion.
AB - Platelet transfusion can elicit alloimmune responses leading to alloantibody
formation against donor-specific polymorphic residues, ultimately resulting in
platelet transfusion refractoriness. Universal leukoreduction significantly
reduced the frequency of alloimmunization after platelet transfusion, thereby
showing the importance of white blood cells (WBCs) in inducing this alloresponse.
It is, however, unknown if the residual risk for alloimmunization is caused by
WBCs remaining after leukoreduction or if alloimmunization can be induced by
platelets themselves. This study investigated the capacity of platelets to induce
alloimmunization and identified potential product-related risk factors for
alloimmunization. First, internalization of allogeneic platelets by dendritic
cells (DCs) was demonstrated by confocal microscopy. Second, after
internalization, presentation of platelet-derived peptides was shown by mass
spectrometry analysis of human leukocytes antigen (HLA)-DR eluted peptides.
Third, platelet-loaded DCs induced platelet-specific CD4 T cell responses.
Altogether, this indicates a platelet-specific ability to induce
alloimmunization. Therefore, factors enhancing platelet internalization may be
identified as risk factor for alloimmunization by platelet concentrates. To
investigate if storage of platelets is such a risk factor, internalization of
stored platelets was compared with fresh platelets and showed enhanced
internalization of stored platelets. Storage-induced apoptosis and accompanied
phosphatidylserine exposure seemed to be instrumental for this. Indeed, DCs pre
incubated with apoptotic platelets induced the strongest IFN-gamma production by
CD4 T cells compared with pre-incubation with untreated or activated platelets.
In conclusion, this study shows the capacity of platelets to induce platelet
specific alloimmune responses. Furthermore, storage-induced apoptosis of
platelets is identified as potential risk factor for alloimmunization after
platelet transfusions.
PMID- 29951052
TI - Correlates of Follicular Helper Bias in the CD4 T Cell Response to a Retroviral
Antigen.
AB - CD4+ T cell differentiation is influenced by a plethora of intrinsic and
extrinsic factors, providing the immune system with the ability to tailor its
response according to specific stimuli. Indeed, different classes of pathogens
may induce a distinct balance of CD4+ T cell differentiation programmes. Here, we
report an uncommonly strong bias toward follicular helper (Tfh) differentiation
of CD4+ T cells reactive with a retroviral envelope glycoprotein model antigen,
presented in its natural context during retroviral infection. Conversely, the
response to the same antigen, presented in different immunization regimens,
elicited a response typically balanced between Tfh and T helper 1 cells.
Comprehensive quantitation of variables known to influence Tfh differentiation
revealed the closest correlation with the strength of T cell receptor (TCR)
signaling, leading to PD-1 expression, but not with surface TCR downregulation,
irrespective of TCR clonotypic avidity. In contrast, strong TCR signaling leading
to TCR downregulation and induction of LAG3 expression in high TCR avidity
clonotypes restrained CD4+ T cell commitment and further differentiation.
Finally, stunted Th1 differentiation, correlating with limited IL-2 availability
in retroviral infection, provided permissive conditions for Tfh development,
suggesting that Tfh differentiation is the default program of envelope-reactive
CD4+ T cells.
PMID- 29951053
TI - Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse
Model of Autoimmune Alopecia Areata.
AB - The treatment of autoimmune diseases still poses a major challenge, frequently
relying on non-specific immunosuppressive drugs. Current efforts aim at
reestablishing self tolerance using immune cells with suppressive activity like
the regulatory T cells (Treg) or the myeloid-derived suppressor cells (MDSC). We
have demonstrated therapeutic efficacy of MDSC in mouse Alopecia Areata (AA). In
the same AA model, we now asked whether MDSC exosomes (MDSC-Exo) can replace
MDSC. MDSC-Exo from bone marrow cells (BMC) cultures of healthy donors could
substantially facilitate treatment. With knowledge on MDSC-Exo being limited,
their suitability needs to be verified in advance. Protein marker profiles
suggest comparability of BMC- to ex vivo collected inflammatory MDSC/MDSC-Exo in
mice with a chronic contact dermatitis, which is a therapeutic option in AA.
Proteome analyses substantiated a large overlap of function-relevant molecules in
MDSC and MDSC-Exo. Furthermore, MDSC-Exo are taken up by T cells, macrophages,
NK, and most avidly by Treg and MDSC-Exo uptake exceeds binding of MDSC
themselves. In AA mice, MDSC-Exo preferentially target skin-draining lymph nodes
and cells in the vicinity of remnant hair follicles. MDSC-Exo uptake is
accompanied by a strong increase in Treg, reduced T helper proliferation,
mitigated cytotoxic activity, and a slight increase in lymphocyte apoptosis.
Repeated MDSC-Exo application in florid AA prevented progression and sufficed for
partial hair regrowth. Deep sequencing of lymphocyte mRNA from these mice
revealed a significant increase in immunoregulatory mRNA, including FoxP3 and
arginase 1. Downregulated mRNA was preferentially engaged in prohibiting T cell
hyperreactivity. Taken together, proteome analysis provided important insights
into potential MDSC-Exo activities, these Exo preferentially homing into AA
affected organs. Most importantly, changes in leukocyte mRNA seen after treatment
of AA mice with MDSC-Exo sustainably supports the strong impact on the adaptive
and the non-adaptive immune system, with Treg expansion being a dominant feature.
Thus, MDSC-Exo could potentially serve as therapeutic agents in treating AA and
other autoimmune diseases.
PMID- 29951055
TI - Altered Functions and Interactions of Glaucoma-Associated Mutants of Optineurin.
AB - Optineurin (OPTN) is an adaptor protein that is involved in mediating a variety
of cellular processes such as signaling, vesicle trafficking, and autophagy.
Certain mutations in OPTN (gene OPTN) are associated with primary open angle
glaucoma, a leading cause of irreversible blindness, and amyotrophic lateral
sclerosis, a fatal motor neuron disease. Glaucoma-associated mutations of OPTN
are mostly missense mutations. OPTN mediates its functions by interacting with
various proteins and altered interactions of OPTN mutants with various proteins
primarily contribute to functional defects. It interacts with Rab8, myosin VI,
Huntigtin, TBC1D17, and transferrin receptor to mediate various membrane vesicle
trafficking pathways. It is an autophagy receptor that mediates cargo-selective
as well as non-selective autophagy. Glaucoma-associated mutants of OPTN, E50K,
and M98K, cause defective vesicle trafficking, autophagy, and signaling that
contribute to death of retinal ganglion cells (RGCs). Transgenic mice expressing
E50K-OPTN show loss of RGCs and persistent reactive gliosis. TBK1 protein kinase,
which mediates E50K-OPTN and M98K-OPTN induced cell death, is emerging as a
potential drug target. Autoimmunity has been implicated in glaucoma but
involvement of OPTN or its mutants in autoimmnity has not been explored. In this
review, we highlight the main functions of OPTN and how glaucoma-associated
mutants alter these functions. We also discuss some of the controversies, such as
the role of OPTN in signaling to transcription factor NF-kappaB, interferon
signaling, and use of RGC-5 cell line as a cell culture model.
PMID- 29951054
TI - The Role of Mitophagy in Innate Immunity.
AB - Mitochondria are cellular organelles essential for multiple biological processes,
including energy production, metabolites biosynthesis, cell death, and
immunological responses among others. Recent advances in the field of immunology
research reveal the pivotal role of energy metabolism in innate immune cells fate
and function. Therefore, the maintenance of mitochondrial network integrity and
activity is a prerequisite for immune system homeostasis. Mitochondrial selective
autophagy, known as mitophagy, surveils mitochondrial population eliminating
superfluous and/or impaired organelles and mediating cellular survival and
viability in response to injury/trauma and infection. Defective removal of
damaged mitochondria leads to hyperactivation of inflammatory signaling pathways
and subsequently to chronic systemic inflammation and development of inflammatory
diseases. Here, we review the molecular mechanisms of mitophagy and highlight its
critical role in the innate immune system homeostasis.
PMID- 29951056
TI - Adverse Effects of Immunoglobulin Therapy.
AB - Immunoglobulin has been widely used in a variety of diseases, including primary
and secondary immunodeficiency diseases, neuromuscular diseases, and Kawasaki
disease. Although a large number of clinical trials have demonstrated that
immunoglobulin is effective and well tolerated, various adverse effects have been
reported. The majority of these events, such as flushing, headache, malaise,
fever, chills, fatigue and lethargy, are transient and mild. However, some rare
side effects, including renal impairment, thrombosis, arrhythmia, aseptic
meningitis, hemolytic anemia, and transfusion-related acute lung injury (TRALI),
are serious. These adverse effects are associated with specific immunoglobulin
preparations and individual differences. Performing an early assessment of risk
factors, infusing at a slow rate, premedicating, and switching from intravenous
immunoglobulin (IVIG) to subcutaneous immunoglobulin (SCIG) can minimize these
adverse effects. Adverse effects are rarely disabling or fatal, treatment mainly
involves supportive measures, and the majority of affected patients have a good
prognosis.
PMID- 29951057
TI - The Clinical Significance and Potential Role of C-Reactive Protein in Chronic
Inflammatory and Neurodegenerative Diseases.
AB - C-reactive protein (CRP) is an acute-phase protein synthesized by hepatocytes in
response to pro-inflammatory cytokines during inflammatory/infectious processes.
CRP exists in conformationally distinct forms such as the native pentameric CRP
and monomeric CRP (mCRP) and may bind to distinct receptors and lipid rafts and
exhibit different functional properties. It is known as a biomarker of acute
inflammation, but many large-scale prospective studies demonstrate that CRP is
also known to be associated with chronic inflammation. This review is focused on
discussing the clinical significance of CRP in chronic inflammatory and
neurodegenerative diseases, such as cardiovascular disease, type 2 diabetes
mellitus, age-related macular degeneration, hemorrhagic stroke, Alzheimer's
disease, and Parkinson's disease, including recent advances on the implication of
CRP and its forms specifically on the pathogenesis of these diseases. Overall, we
highlight the advances in these areas that may be translated into promising
measures for the diagnosis and treatment of inflammatory diseases.
PMID- 29951058
TI - Hsp70 Suppresses Mitochondrial Reactive Oxygen Species and Preserves Pulmonary
Microvascular Barrier Integrity Following Exposure to Bacterial Toxins.
AB - Pneumonia is a leading cause of death in children and the elderly worldwide,
accounting for 15% of all deaths of children under 5 years old. Streptococcus
pneumoniae is a common and aggressive cause of pneumonia and can also contribute
to meningitis and sepsis. Despite the widespread use of antibiotics, mortality
rates for pneumonia remain unacceptably high in part due to the release of
bacterial toxins. Pneumolysin (PLY) is a cholesterol-dependent toxin that is
produced by Streptococcus, and it is both necessary and sufficient for the
development of the extensive pulmonary permeability edema that underlies acute
lung injury. The mechanisms by which PLY disrupts the pulmonary endothelial
barrier are not fully understood. Previously, we found that reactive oxygen
species (ROS) contribute to the barrier destructive effects of PLY and identified
an unexpected but potent role of Hsp70 in suppressing ROS production. The ability
of Hsp70 to influence PLY-induced barrier dysfunction is not yet described, and
the goal of the current study was to identify whether Hsp70 upregulation is an
effective strategy to protect the lung microvascular endothelial barrier from G+
bacterial toxins. Overexpression of Hsp70 via adenovirus-mediated gene transfer
attenuated PLY-induced increases in permeability in human lung microvascular
endothelial cells (HLMVEC) with no evidence of cytotoxicity. To adopt a more
translational approach, we employed a pharmacological approach using
geranylgeranylacetone (GGA) to acutely upregulate endogenous Hsp70 expression.
Following acute treatment (6 h) with GGA, HLMVECs exposed to PLY displayed
improved cell viability and enhanced endothelial barrier function as measured by
both Electric Cell-substrate Impedance Sensing (ECIS) and transwell permeability
assays compared to control treated cells. PLY promoted increased mitochondrial
ROS, decreased mitochondrial oxygen consumption, and increased caspase 3 cleavage
and cell death, which were collectively improved in cells pretreated with GGA. In
mice, IP pretreatment with GGA 24 h prior to IT administration of PLY resulted in
significantly less Evans Blue Dye extravasation compared to vehicle, indicating
preserved endothelial barrier integrity and suggesting that the acute
upregulation of Hsp70 may be an effective therapeutic approach in the treatment
of lung injury associated with pneumonia.
PMID- 29951059
TI - Regulatory Roles of Invariant Natural Killer T Cells in Adipose Tissue
Inflammation: Defenders Against Obesity-Induced Metabolic Complications.
AB - Adipose tissue is a metabolic organ that plays a central role in controlling
systemic energy homeostasis. Compelling evidence indicates that immune system is
closely linked to healthy physiologic functions and pathologic dysfunction of
adipose tissue. In obesity, the accumulation of pro-inflammatory responses in
adipose tissue subsequently leads to dysfunction of adipose tissue as well as
whole body energy homeostasis. Simultaneously, adipose tissue also activates anti
inflammatory responses in an effort to reduce the unfavorable effects of pro
inflammation. Notably, the interplay between adipocytes and resident invariant
natural killer T (iNKT) cells is a major component of defensive mechanisms of
adipose tissue. iNKT cells are leukocytes that recognize lipids loaded on CD1d as
antigens, whereas most other immune cells are activated by peptide antigens. In
adipose tissue, adipocytes directly interact with iNKT cells by presenting lipid
antigens and stimulate iNKT cell activation to alleviate pro-inflammation. In
this review, we provide an overview of the molecular and cellular determinants of
obesity-induced adipose tissue inflammation. Specifically, we focus on the roles
of iNKT cell-adipocyte interaction in maintaining adipose tissue homeostasis as
well as the consequent modulation in systemic energy metabolism. We also briefly
discuss future research directions regarding the interplay between adipocytes and
adipose iNKT cells in adipose tissue inflammation.
PMID- 29951060
TI - Cell Cycle-Associated CXCR4 Expression in Germinal Center B Cells and Its
Implications on Affinity Maturation.
AB - Adaptation of antibody-mediated immunity occurs in germinal centers (GC). It is
where affinity maturation, class switching, memory and plasma cell
differentiation synergize to generate specific high-affinity antibodies that aid
both to clear and protect against reinfection of invading pathogens. Within GCs,
light and dark zone are two compartments instrumental in regulating this process,
by segregating T cell-dependent selection and differentiation from generation of
GC B cells bearing hypermutated antigen receptors. Spatial segregation of GC B
cells into the two zones relies on the chemokine receptor CXCR4, with textbooks
attributing high and low expression to a dark and light zone phenotype.
Interestingly, this bipolarity is not reflected in the CXCR4 expression profile
of GC B cells, which is highly variable and unimodal, indicating a continuum of
intermediate CXCR4 levels rather than a binary dark or light zone phenotype.
Here, analysis of published BrdU pulse-chase data reveals that throughout cell
cycle, average CXCR4 expression in GC B cells steadily increases close to
twofold, scaling with cell surface area. CXCR4 expression in recently divided GC
B cells in G0/G1 or early S phase shows intermediate levels compared to cells in
G2M phase, consistent with their smaller size. The lowest number of CXCR4
receptors are displayed by relatively aged GC B cells in G0/G1 or early S phase.
The latter, upon progressing through S phase, however, ramp up relative CXCR4
expression twice as much as recently divided cells. Twelve hours after the BrdU
pulse, labeled GC B cells, while initially in S phase, are desynchronized in
terms of cell cycle and match the CXCR4 profile of unlabeled cells. A model is
discussed in which CXCR4 expression in GC B cell increases with cell cycle and
cell surface area, with highest levels in G2 and M phase, coinciding with GC B
cell receptor signaling in G2 and immediately preceding activation-induced
cytidine deaminase (AID) activity in early G1. In the model, GC B cells compete
for CXCL12 expression on the basis of their CXCR4 expression, gaining a relative
advantage as they progress in cell cycle, but loosing the advantage at the moment
they divide.
PMID- 29951061
TI - The Neutralizing Face of Hepatitis C Virus E2 Envelope Glycoprotein.
AB - The high genetic variability of hepatitis C virus, together with the high level
of glycosylation on the viral envelope proteins shielding potential neutralizing
epitopes, pose a difficult challenge for vaccine development. An effective
hepatitis C virus (HCV) vaccine must target conserved epitopes and the HCV E2
glycoprotein is the main target for such neutralizing antibodies (NAbs). Recent
structural investigations highlight the presence of a highly conserved and
accessible surface on E2 that is devoid of N-linked glycans and known as the E2
neutralizing face. This face is defined as a hydrophobic surface comprising the
front layer (FL) and the CD81 binding loop (CD81bl) that overlap with the CD81
receptor binding site on E2. The neutralizing face consists of highly conserved
residues for recognition by cross-NAbs, yet it appears to be high
conformationally flexible, thereby presenting a moving target for NAbs. Three
main overlapping neutralizing sites have been identified in the neutralizing
face: antigenic site 412 (AS412), antigenic site 434 (AS434), and antigenic
region 3 (AR3). Here, we review the structural analyses of these neutralizing
sites, either as recombinant E2 or epitope-derived linear peptides in complex
with bNAbs, to understand the functional and preferred conformations for
neutralization, and for viral escape. Collectively, these studies provide a
foundation and molecular templates to facilitate structure-based approaches for
HCV vaccine development.
PMID- 29951062
TI - V(D)J Rearrangement Is Dispensable for Producing CDR-H3 Sequence Diversity in a
Gene Converting Species.
AB - An important characteristic of chickens is that the antibody repertoire is based
on a single framework, with diversity found mainly in the CDRs of the light and
heavy chain variable regions. Despite this apparent limitation in the antibody
repertoire, high-affinity antibodies can be raised to a wide variety of targets,
including those that are highly conserved. Transgenic chickens have previously
been generated that express a humanized antibody repertoire, with a single
framework that incorporates diversity by the process of gene conversion, as in
wild-type chickens. Here, we compare the sequences and antibodies that are
generated purely by gene conversion/somatic hypermutation of a pre-rearranged
heavy chain, with the diversity obtained by V(D)J rearrangement followed by gene
conversion and somatic hypermutation. In a gene converting species, CDR-H3
lengths are more variable with V(D)J rearrangement, but similar levels of amino
acid diversity are obtainable with gene conversion/somatic hypermutation alone.
PMID- 29951063
TI - Peculiar Expression of CD3-Epsilon in Kidney of Ginbuna Crucian Carp.
AB - TCR/CD3 complex is composed of the disulfide-linked TCR-alphabeta heterodimer
that recognizes the antigen as a peptide presented by the MHC, and non-covalently
paired CD3gammaepsilon- and deltaepsilon-chains together with disulfide-linked
zeta-chain homodimers. The CD3 chains play key roles in T cell development and T
cell activation. In the present study, we found nor or extremely lower expression
of CD3epsilon in head- and trunk-kidney lymphocytes by flow cytometric analysis,
while CD3epsilon was expressed at the normal level in lymphocytes from thymus,
spleen, intestine, gill, and peripheral blood. Furthermore, CD4-1+ and CD8alpha+
T cells from kidney express Zap-70, but not CD3epsilon, while the T cells from
other tissues express both Zap-70 and CD3epsilon, although expression of
CD3epsilon was low. Quantitative analysis of mRNA expression revealed that the
expression level of T cell-related genes including tcrb, cd3epsilon, zap-70, and
lck in CD4-1+ and CD8alpha+ T cells was not different between kidney and spleen.
Western blot analysis showed that CD3epsilon band was detected in the cell
lysates of spleen but not kidney. To be interested, CD3epsilon-positive cells
greatly increased after 24 h in in vitro culture of kidney leukocytes.
Furthermore, expression of CD3epsilon in both transferred kidney and spleen
leukocytes was not detected or very low in kidney, while both leukocytes
expressed CD3epsilon at normal level in spleen when kidney and spleen leukocytes
were injected into the isogeneic recipient. Lower expression of CD3epsilon was
also found in kidney T lymphocytes of goldfish and carp. These results indicate
that kidney lymphocytes express no or lower level of CD3epsilon protein in the
kidney, although the mRNA of the gene was expressed. Here, we discuss this
phenomenon from the point of function of kidney as reservoir for T lymphocytes in
teleost, which lacks lymph node and bone marrow.
PMID- 29951065
TI - Monocyte-Derived Dendritic Cells Differentiated in the Presence of Lenalidomide
Display a Semi-Mature Phenotype, Enhanced Phagocytic Capacity, and Th1
Polarization Capability.
AB - Lenalidomide is an analog of thalidomide, with potent anticancer activity
demonstrated in several hematological malignancies. It has immunomodulatory
properties, being able to enhance the activation of different types of immune
cells, which results in antitumor activities. Dendritic cells (DCs) are pivotal
in the immune response, and different immunotherapeutic approaches targeting
these cells are being developed. Since little is known about the effect of
lenalidomide on DCs, the goal of the present work was to investigate the
phenotype and function of human monocyte-derived DCs differentiated in the
presence of lenalidomide (L-DCs). Our results showed that L-DCs display a unique
phenotype, with increased cell surface expression of some maturation markers such
as CD1d, CD83, CD86, and HLA-DR. This phenotype correlates with a lower
expression of the E3 ubiquitin-ligase MARCH-I in L-DCs, upregulating the cell
surface expression of CD86 and HLA-DR. In addition, immature L-DCs express higher
amounts of DC-SIGN on the cell surface than control immature DCs. After LPS
stimulation, production of IL-6 and TNF-alpha was severely decreased, whereas IL
12 and IL-10 secretion was dramatically upregulated in L-DCs, compared to that in
the controls. Functionally, L-DCs are more effectively recognized by NKT cells in
cytotoxicity experiments. Furthermore, L-DCs display higher opsonin-independent
antigen uptake capability than control DCs. Mixed lymphocyte reaction experiments
showed that L-DCs could stimulate naive CD4 T-cells, polarizing them toward a
predominant Th1 phenotype. In summary, DCs derived from monocytes in the presence
of lenalidomide present a semi-mature phenotype, increased phagocytic capacity,
reduced production of proinflammatory cytokines, and the ability to polarize T
cells toward predominant Th1-type responses; these are qualities that might be
useful in the development of new immunotherapeutic treatments.
PMID- 29951064
TI - Systematic Methodological Evaluation of a Multiplex Bead-Based Flow Cytometry
Assay for Detection of Extracellular Vesicle Surface Signatures.
AB - Extracellular vesicles (EVs) can be harvested from cell culture supernatants and
from all body fluids. EVs can be conceptually classified based on their size and
biogenesis as exosomes and microvesicles. Nowadays, it is however commonly
accepted in the field that there is a much higher degree of heterogeneity within
these two subgroups than previously thought. For instance, the surface marker
profile of EVs is likely dependent on the cell source, the cell's activation
status, and multiple other parameters. Within recent years, several new methods
and assays to study EV heterogeneity in terms of surface markers have been
described; most of them are being based on flow cytometry. Unfortunately, such
methods generally require dedicated instrumentation, are time-consuming and
demand extensive operator expertise for sample preparation, acquisition, and data
analysis. In this study, we have systematically evaluated and explored the use of
a multiplex bead-based flow cytometric assay which is compatible with most
standard flow cytometers and facilitates a robust semi-quantitative detection of
37 different potential EV surface markers in one sample simultaneously. First,
assay variability, sample stability over time, and dynamic range were assessed
together with the limitations of this assay in terms of EV input quantity
required for detection of differently abundant surface markers. Next, the
potential effects of EV origin, sample preparation, and quality of the EV sample
on the assay were evaluated. The findings indicate that this multiplex bead-based
assay is generally suitable to detect, quantify, and compare EV surface
signatures in various sample types, including unprocessed cell culture
supernatants, cell culture-derived EVs isolated by different methods, and
biological fluids. Furthermore, the use and limitations of this assay to assess
heterogeneities in EV surface signatures was explored by combining different sets
of detection antibodies in EV samples derived from different cell lines and
subsets of rare cells. Taken together, this validated multiplex bead-based flow
cytometric assay allows robust, sensitive, and reproducible detection of EV
surface marker expression in various sample types in a semi-quantitative way and
will be highly valuable for many researchers in the EV field in different
experimental contexts.
PMID- 29951066
TI - Correlation Between the Hepatic Expression of Human MicroRNA hsa-miR-125a-5p and
the Progression of Fibrosis in Patients With Overt and Occult HBV Infection.
AB - Aims: To evaluate the correlation between the hepatic expression pattern of hsa
miR-125a-5p and HBV-DNA and the progression of fibrosis in patients with overt or
occult HBV infection. Methods: We enrolled all the HBsAg-positive treatment naive
patients (overt HBV group) and all the HBsAg-negative patients with
hepatocellular carcinoma and with a positive HBV-DNA in their hepatic tissue
(occult HBV group), who underwent a diagnostic liver biopsy between April 2007
and April 2015. Tissue concentrations of HBV-DNA and hsa-miR-125a-5p were then
analyzed by real-time quantitative PCR. Necroinflammatory activity and fibrosis
were evaluated according to the Ishak score. Results: During the study period, we
enrolled 64 patients with overt and 10 patients with occult HBV infection. In the
overt HBV group, 35 of 64 (54.7%) showed a mild fibrosis (staging 0-2), 17
(26.6%) a moderate fibrosis (staging 3-4), while the remaining 12 (18.7%) had a
cirrhosis. All patients in the occult HBV group were cirrhotic. Patients with
more advanced fibrosis stage showed a higher mean age when compared with those
with mild (p < 0.00001) or moderate fibrosis (p < 0.00001) and were more
frequently male than patients with staging 0-2 (p = 0.04). Similarly, patients
with occult B infection were older than HBsAg-positive patients. Liver
concentrations of miR-125a-5p were significantly higher in patients with
cirrhosis (9.75 +/- 4.42 AU) when compared with patients with mild (1.39 +/-
0.94, p = 0.0002) or moderate fibrosis (2.43 +/- 2.18, p = 0.0006) and were
moderately higher in occult than in overt HBV infection (p = 0.09). Moreover, we
found an inverse correlation, although not statistically significant, between the
tissue HBV-DNA levels and the staging of fibrosis. Conclusion: This study
suggests a correlation between the tissue expression of hsa-miR-125a-5p and the
progression of liver damage in a group of patients with occult or overt HBV
infection. If confirmed, these data suggest the hsa-miR-125a-5p may be a novel
biomarker of hepatic damage.
PMID- 29951067
TI - Myocarditis: An Interleukin-1-Mediated Disease?
PMID- 29951068
TI - The Neuropeptides Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase
Activating Polypeptide Control HIV-1 Infection in Macrophages Through Activation
of Protein Kinases A and C.
AB - Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating
polypeptide (PACAP) are highly similar neuropeptides present in several tissues,
endowed with immunoregulatory functions and other systemic effects. We previously
reported that both neuropeptides reduce viral production in HIV-1-infected
primary macrophages, with the participation of beta-chemokines and IL-10, and now
we describe molecular mechanisms engaged in this activity. Macrophages exposed to
VIP or PACAP before HIV-1 infection showed resistance to viral replication,
comparable to that observed when the cells were treated after infection. Also,
multiple treatments with a suboptimal dose of VIP or PACAP after macrophage
infection resulted in a decline of virus production similar to the inhibition
promoted by a single exposure to the optimal inhibitory concentration. Cellular
signaling pathways involving cAMP production and activation of protein kinases A
and C were critical components of the VIP and PACAP anti-HIV-1 effects. Analysis
of the transcription factors and the transcriptional/cell cycle regulators showed
that VIP and PACAP induced cAMP response element-binding protein activation,
inhibited NF-kB, and reduced Cyclin D1 levels in HIV-1-infected cells.
Remarkably, VIP and PACAP promoted G-to-A mutations in the HIV-1 provirus,
matching those derived from the activity of the APOBEC family of viral
restriction factors, and reduced viral infectivity. In conclusion, our findings
strengthen the antiretroviral potential of VIP and PACAP and point to new
therapeutic approaches to control the progression of HIV-1 infection.
PMID- 29951069
TI - Common Features of Regulatory T Cell Specialization During Th1 Responses.
AB - CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing
excessive immune responses. In the context of Th1 immune responses, co-expression
of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to
control Th1 responses. T-bet-dependent expression of CXCR3 directs Treg cells to
the site of inflammation. However, the suppressive mediators enabling effective
control of Th1 responses at this site are unknown. In this study, we determined
the signature of CXCR3+ Treg cells arising in Th1 settings and defined universal
features of Treg cells in this context using multiple Th1-dominated infection
models. Our analysis defined a set of Th1-specific co-inhibitory receptors and
cytotoxic molecules that are specifically expressed in Treg cells during Th1
immune responses in mice and humans. Among these, we identified the novel co
inhibitory receptor CD85k as a functional predictor for Treg-mediated suppression
specifically of Th1 responses, which could be explored therapeutically for
selective immune suppression in autoimmunity.
PMID- 29951071
TI - Arabidopsis IQM4, a Novel Calmodulin-Binding Protein, Is Involved With Seed
Dormancy and Germination in Arabidopsis.
AB - Seed dormancy and germination are regulated by complex mechanisms controlled by
diverse hormones and environmental cues. Abscisic acid (ABA) promotes seed
dormancy and inhibits seed germination and post-germination growth. Calmodulin
(CaM) signals are involved with the inhibition of ABA during seed germination and
seedling growth. In this study, we showed that Arabidopsis thaliana IQM4 could
bind with calmodulin 5 (CaM5) both in vitro and in vivo, and that the interaction
was the Ca2+-independent type. The IQM4 protein was localized in the chloroplast
and the IQM4 gene was expressed in most tissues, especially the embryo and
germinated seedlings. The T-DNA insertion mutants of IQM4 exhibited the reduced
primary seed dormancy and lower ABA levels compared with wild type seeds.
Moreover, IQM4 plays key roles in modulating the responses to ABA, salt, and
osmotic stress during seed germination and post-germination growth. T-DNA
insertion mutants exhibited ABA-insensitive and salt-hypersensitive phenotypes
during seed germination and post-germination growth, whereas IQM4-overexpressing
lines had ABA- and osmotic-hypersensitive, and salt-insensitive phenotypes. Gene
expression analyses showed that mutation of IQM4 inhibited the expression of ABA
biosynthetic genes NCED6 and NCED9, and seed maturation regulators LEC1, LEC2,
ABI3, and ABI5 during the silique development, as well as promoted the expression
of WRKY40 and inhibited that of ABI5 in ABA-regulated seed germination. These
observations suggest that IQM4 is a novel Ca2+-independent CaM-binding protein,
which is positively involved with seed dormancy and germination in Arabidopsis.
PMID- 29951072
TI - Biofortification of Cereals With Foliar Selenium and Iodine Could Reduce
Hypothyroidism.
AB - Concurrent selenium and iodine deficiencies are widespread, in both developing
and developed countries. Salt iodisation is insufficient to ensure global iodine
adequacy, with an estimated one-third of humanity at risk of hypothyroidism and
associated iodine deficiency disorders (IDD). Agronomic biofortification of food
crops, especially staples such as cereals, which are consumed widely, may be an
effective component of a food system strategy to reduce selenium and iodine
malnutrition. Iodine and selenium are needed in the optimum intake range for
thyroid health, hence joint biofortification makes sense for areas deficient in
both. Foliar application is recommended as the most effective, efficient, least
wasteful method for selenium and iodine biofortification. Currently, selenium is
easier to increase in grain, fruit, and storage roots by this method, being more
phloem mobile than iodine. Nevertheless, strategic timing (around heading is
usually best), use of surfactants and co-application with potassium nitrate can
increase the effectiveness of foliar iodine biofortification. More research is
needed on iodine transporters and iodine volatilisation in plants,
bioavailability of iodine in biofortified plant products, and roles for nano
selenium and iodine in biofortification. For adoption, farmers need an incentive
such as access to a premium functional food market, a subsidy or increased grain
yield resulting from possible synergies with co-applied fertilisers, enhancers,
fungicides, and insecticides. Further research is needed to inform these aspects
of foliar agronomic biofortification.
PMID- 29951073
TI - Root Differentiation of Agricultural Plant Cultivars and Proveniences Using FTIR
Spectroscopy.
AB - The differentiation of roots of agricultural species is desired for a deeper
understanding of the belowground root interaction which helps to understand the
complex interaction in intercropping and crop-weed systems. The roots can be
reliably differentiated via Fourier transform infrared spectroscopy with
attenuated total reflection (FTIR-ATR). In two replicated greenhouse experiments,
six pea cultivars, five oat cultivars as well as seven maize cultivars and five
barnyard grass proveniences (n = 10 plants/cultivar or provenience) were grown
under controlled conditions. One root of each plant was harvested and five
different root segments of each root were separated, dried and measured with FTIR
ATR spectroscopy. The results showed that, firstly, the root spectra of single
pea and single oat cultivars as well as single maize and single barnyard grass
cultivars/proveniences separated species-specific in cluster analyses. In the
majority of cases the species separation was correct, but in a few cases, the
spectra of the root tips had to be omitted to ensure the precise separation
between the species. Therefore, species differentiation is possible regardless of
the cultivar or provenience. Consequently, all tested cultivars of pea and oat
spectra were analyzed together and separated within a cluster analysis according
to their affiliated species. The same result was found in a cluster analysis with
maize and barnyard grass spectra. Secondly, a cluster analysis with all species
(pea, oat, maize and barnyard grass) was performed. The species split up species
specific and formed a dicotyledonous pea cluster and a monocotyledonous cluster
subdivided in oat, maize and barnyard grass subclusters. Thirdly, cultivar or
provenience differentiations within one species were possible in one of the two
replicated experiments. But these separations were less resilient.
PMID- 29951070
TI - The Role and Molecular Mechanism of Action of Surfactant Protein D in Innate Host
Defense Against Influenza A Virus.
AB - Influenza A viruses (IAVs) continue to pose major risks of morbidity and
mortality during yearly epidemics and periodic pandemics. The genomic instability
of IAV allows it to evade adaptive immune responses developed during prior
infection. Of particular concern are pandemics which result from wholesale
incorporation of viral genome sections from animal sources. These pandemic
strains are radically different from circulating human strains and pose great
risk for the human population. For these reasons, innate immunity plays a strong
role in the initial containment of IAV infection. Soluble inhibitors present in
respiratory lining fluids and blood provide a level of early protection against
IAV. In general, these inhibitors act by binding to the viral hemagglutinin (HA).
Surfactant protein D (SP-D) and mannose-binding lectin (MBL) attach to
mannosylated glycans on the HA in a calcium dependent manner. In contrast,
surfactant protein A, ficolins, and other inhibitors present sialic acid rich
ligands to which the HA can bind. Among these inhibitors, SP-D seems to be the
most potent due to its specific mode of binding to viral carbohydrates and its
ability to strongly aggregate viral particles. We have studied specific
properties of the N-terminal and collagen domain of SP-D that enable formation of
highly multimerized molecules and cooperative binding among the multiple trimeric
lectin domains in the protein. In addition, we have studied in depth the lectin
activity of SP-D through expression of isolated lectin domains and targeted
mutations of the SP-D lectin binding site. Through modifying specific residues
around the saccharide binding pocket, antiviral activity of isolated lectin
domains of SP-D can be markedly increased for seasonal strains of IAV. Wild-type
SP-D causes little inhibition of pandemic IAV, but mutated versions of SP-D were
able to inhibit pandemic IAV through enhanced binding to the reduced number of
mannosylated glycans present on the HA of these strains. Through collaborative
studies involving crystallography of isolated lectin domains of SP-D, glycomics
analysis of the HA, and molecular modeling, the mechanism of binding of wild type
and mutant forms of SP-D have been determined. These studies could guide
investigation of the interactions of SP-D with other pathogens.
PMID- 29951074
TI - Light Is More Important Than Nutrient Ratios of Fertilization for Cymodocea
nodosa Seedling Development.
AB - Restoration of seagrass beds through seedlings is an alternative to the
transplantation of adult plants that reduces the impact over donor areas and
increases the genetic variability of restored meadows. To improve the use of
Cymodocea nodosa seedlings, obtained from seeds germinated in vitro, in
restoration programs, we investigated the ammonium and phosphate uptake rates of
seedlings, and the synergistic effects of light levels (20 and 200 MUmol quanta m
2 s-1) and different nitrogen to phosphorus molar ratios (40 MUM N:10 MUM P, 25
MUM N:25 MUM P, and 10 MUM N:40 MUM P) on the photosynthetic activity and growth
of seedlings. The nutrient content of seedlings was also compared to the seed
nutrient reserves to assess the relative importance of external nutrient uptake
for seedling development. Eighty two percent of the seeds germinated after 48
days at a mean rate of 1.5 seeds per day. All seedlings under all treatments
survived and grew during the 4 weeks of the experiment. Seedlings of C. nodosa
acquired ammonium and phosphate from the incubation media while still attached to
the seed, at rates of about twice of adult plants. The relevance of external
nutrient uptake was further highlighted by the observation that seedlings'
tissues were richer in nitrogen and phosphorus than non-germinated seeds. The
uptake of ammonium followed saturation kinetics with a half saturation constant
of 32 MUM whereas the uptake of phosphate increased linearly with nutrient
concentration within the range tested (5 - 100 MUM). Light was more important
than the nutrient ratio of fertilization for the successful development of the
young seedlings. The seedlings' photosynthetic and growth rates were about 20%
higher in the high light treatment, whereas different nitrogen to phosphorus
ratios did not significantly affect growth. The photosynthetic responses of the
seedlings to changes in the light level and their capacity to use external
nutrient sources showed that seedlings of C. nodosa have the ability to rapidly
acclimate to the surrounding light and nutrient environment while still attached
to the seeds. C. nodosa seedlings experiencing fertilization under low light
levels showed slightly enhanced growth if nourished with a balanced formulation,
whereas a slight increase in growth was also observed with unbalanced
formulations under a higher light level. Our results highlight the importance of
high light availability at the seedling restoration sites.
PMID- 29951075
TI - Using RT-qPCR, Proteomics, and Microscopy to Unravel the Spatio-Temporal
Expression and Subcellular Localization of Hordoindolines Across Development in
Barley Endosperm.
AB - Hordeum vulgare (barley) hordoindolines (HINs), HINa, HINb1, and HINb2, are
orthologous proteins of wheat puroindolines (PINs) that are small, basic,
cysteine-rich seed-specific proteins and responsible for grain hardness. Grain
hardness is, next to its protein content, a major quality trait. In barley, HINb
is most highly expressed in the mid-stage developed endosperm and is associated
with both major endosperm texture and grain hardness. However, data required to
understand the spatio-temporal dynamics of HIN transcripts and HIN protein
regulation during grain filling processes are missing. Using reverse
transcription quantitative PCR (RT-qPCR) and proteomics, we analyzed HIN
transcript and HIN protein abundance from whole seeds (WSs) at four [6 days after
pollination (dap), 10, 12, and >=20 dap] as well as from aleurone, subaleurone,
and starchy endosperm at two (12 and >=20 dap) developmental stages. At the WS
level, results from RT-qPCR, proteomics, and western blot showed a continuous
increase of HIN transcript and HIN protein abundance across these four
developmental stages. Miroscopic studies revealed HIN localization mainly at the
vacuolar membrane in the aleurone, at protein bodies (PBs) in subaleurone and at
the periphery of starch granules in the starchy endosperm. Laser microdissetion
(LMD) proteomic analyses identified HINb2 as the most prominent HIN protein in
starchy endosperm at >=20 dap. Additionally, our quantification data revealed a
poor correlation between transcript and protein levels of HINs in subaleurone
during development. Here, we correlated data achieved by RT-qPCR, proteomics, and
microscopy that reveal different expression and localization pattern of HINs in
each layer during barley endosperm development. This indicates a contribution of
each tissue to the regulation of HINs during grain filling. The effect of the
high protein abundance of HINs in the starchy endosperm and their localization at
the periphery of starch granules at late development stages at the cereal-based
end-product quality is discussed. Understanding the spatio-temporal regulated
HINs is essential to improve barley quality traits for high end-product quality,
as hard texture of the barley grain is regulated by the ratio between HINb/HINa.
PMID- 29951076
TI - Meiotic Studies on Combinations of Chromosomes With Different Sized Centromeres
in Maize.
AB - Multiple centromere misdivision derivatives of a translocation between the
supernumerary B chromosome and the short arm of chromosome 9 (TB-9Sb) permit
investigation of how centromeres of different sizes behave in meiosis in
opposition or in competition with each other. In the first analysis,
heterozygotes were produced between the normal TB-9Sb and derivatives of it that
resulted from centromere misdivision that reduced the amounts of centromeric DNA.
These heterozygotes could test whether these drastic differences would result in
meiotic drive of the larger chromosome in female meiosis. Cytological
determinations of the segregation of large and small centromeres among thousands
of progeny of four combinations were made. The recovery of the larger centromere
was at a few percent higher frequency in two of four combinations. However,
examination of phosphorylated histone H2A-Thr133, a characteristic of active
centromeres, showed a lack of correlation with the size of the centromeric DNA,
suggesting an expansion of the basal protein features of the kinetochore in two
of the three cases despite the reduction in the size of the underlying DNA. In
the second analysis, plants containing different sizes of the B chromosome
centromere were crossed to plants with TB-9Sb with a foldback duplication of 9S
(TB-9Sb-Dp9). In the progeny, plants containing large and small versions of the B
chromosome centromere were selected by FISH. A meiotic "tug of war" occurred in
hybrid combinations by recombination between the normal 9S and the foldback
duplication in those cases in which pairing occurred. Such pairing and
recombination produce anaphase I bridges but in some cases the large and small
centromeres progressed to the same pole. In one combination, new dicentric
chromosomes were found in the progeny. Collectively, the results indicate that
the size of the underlying DNA of a centromere does not dramatically affect its
segregation properties or its ability to progress to the poles in meiosis
potentially because the biochemical features of centromeres adjust to the
cellular conditions.
PMID- 29951077
TI - Zucchini Yellow Mosaic Virus Infection Limits Establishment and Severity of
Powdery Mildew in Wild Populations of Cucurbita pepo.
AB - Few studies have examined the combined effect of multiple parasites on host
fitness. Previous work in the Cucurbita pepo pathosystem indicates that infection
with Zucchini yellow mosaic virus (ZYMV) reduces exposure to a second insect
vectored parasite (Erwinia tracheiphila). In this study, we performed two large
scale field experiments employing wild gourds (Cucurbita pepo ssp. texana),
including plants with a highly introgressed transgene conferring resistance to
ZYMV, to examine the interaction of ZYMV and powdery mildew, a common fungal
disease. We found that ZYMV-infected plants are more resistant to powdery mildew
(i.e., less likely to experience powdery mildew infection and when infected with
powdery mildew, have reduced severity of powdery mildew symptoms). As a
consequence, during widespread viral epidemics, proportionally more transgenic
plants get powdery mildew than non-transgenic plants, potentially mitigating the
benefits of the transgene. A greenhouse study using ZYMV-inoculated and non
inoculated controls (non-transgenic plants) revealed that ZYMV-infected plants
were more resistant to powdery mildew than controls, suggesting that the
transgene itself had no direct effect on the powdery mildew resistance in our
field study. Additionally, we found evidence of elevated levels of salicylic
acid, a phytohormone that mediates anti-pathogen defenses, in ZYMV-infected
plants, suggesting that viral infection induces a plant immune response (systemic
acquired resistance), thereby reducing plant susceptibility to powdery mildew
infection.
PMID- 29951079
TI - Heat Priming During Early Reproductive Stages Enhances Thermo-Tolerance to Post
anthesis Heat Stress via Improving Photosynthesis and Plant Productivity in
Winter Wheat (Triticum aestivum L.).
AB - Heat stress during grain filling substantially decreases wheat productivity;
thus, to ensure food security, heat tolerance in wheat needs to be developed. In
this study, we evaluated the effect of heat priming applied during the stem
elongation stage, booting and anthesis, followed by 5 days of severe heat stress
(a 7.86 degrees C rise in temperature) during the grain-filling stage on
physiological activities and grain yield of winter wheat in pot experiments
during the 2015-2017 growing seasons using the winter wheat cultivars Yangmai 18
(a vernal type) and Yannong 19 (a facultative type). Compared with the damage
observed in non-primed plants, heat priming during the stem-elongation stage and
booting significantly prevented the grain-yield damage caused by heat stress
during grain filling. Heat-primed plants displayed higher sucrose contents and
sucrose-phosphate activity in leaves and greater above-ground dry matter than non
primed plants. Priming during stem elongation and booting led to increased
photosynthetic capacity, stomatal conductance and chlorophyll contents in
comparison with non-priming. Improved tolerance to heat stress due to the
enhanced activities of antioxidant enzymes superoxide dismutase and peroxidase
and reductions in reactive oxygen species and malondialdehyde production was
observed in primed plants compared with non-primed plants of both cultivars. The
positive effect of heat priming on the response to heat stress during grain
filling was more pronounced in plants primed at the booting stage than in those
primed at the stem-elongation or anthesis stage. Moreover, the vernal-type
Yangmai 18 benefited more from heat priming than did Yannong 19, as evidenced by
its higher productivity. We conclude that heat priming during early reproductive
stage growth can improve post-anthesis heat tolerance in winter wheat.
PMID- 29951078
TI - The Role of Tomato WRKY Genes in Plant Responses to Combined Abiotic and Biotic
Stresses.
AB - In the field, plants constantly face a plethora of abiotic and biotic stresses
that can impart detrimental effects on plants. In response to multiple stresses,
plants can rapidly reprogram their transcriptome through a tightly regulated and
highly dynamic regulatory network where WRKY transcription factors can act as
activators or repressors. WRKY transcription factors have diverse biological
functions in plants, but most notably are key players in plant responses to
biotic and abiotic stresses. In tomato there are 83 WRKY genes identified. Here
we review recent progress on functions of these tomato WRKY genes and their
homologs in other plant species, such as Arabidopsis and rice, with a special
focus on their involvement in responses to abiotic and biotic stresses. In
particular, we highlight WRKY genes that play a role in plant responses to a
combination of abiotic and biotic stresses.
PMID- 29951080
TI - Inferring Connectivity Range in Submerged Aquatic Populations (Ruppia L.) Along
European Coastal Lagoons From Genetic Imprint and Simulated Dispersal
Trajectories.
AB - Coastal salt- and brackish water lagoons are unique shallow habitats
characterized by beds of submerged seagrasses and salt-tolerant Ruppia species.
Established long-term and large-scale patterns of connectivity in lagoon systems
can be strongly determined by patterns of nearshore and coastal currents next to
local bird-mediated seed dispersal. Despite the importance of dispersal in
landscape ecology, characterizing patterns of connectivity remains challenging in
aquatic systems. Here, we aimed at inferring connectivity distances of Ruppia
cirrhosa along European coastal lagoons using a population genetic imprint and
modeled dispersal trajectories using an eddy-resolving numerical ocean model that
includes tidal forcing. We investigated 1,303 individuals of 46 populations
alongside subbasins of the Mediterranean (Balearic, Tyrrhenian, Ionian) and the
Atlantic to Baltic Sea coastline over maximum distances of 563-2,684 km. Ten
microsatellite loci under an autotetraploid condition revealed a mixed sexual and
vegetative reproduction mode. A pairwise FST permutation test of populations
revealed high levels of historical connectivity only for distance classes up to
104-280 km. Since full range analysis was not fully explanatory, we assessed
connectivity in more detail at coastline and subbasin level using four
approaches. Firstly, a regression over restricted geographical distances (300 km)
was done though remained comparable to full range analysis. Secondly, piecewise
linear regression analyses yielded much better explained variance but the
obtained breakpoints were shifted toward greater geographical distances due to a
flat slope of regression lines that most likely reflect genetic drift. Thirdly,
classification and regression tree analyses revealed threshold values of 47-179
km. Finally, simulated ocean surface dispersal trajectories for propagules with
floating periods of 1-4 weeks, were congruent with inferred distances, a spatial
Bayesian admixed gene pool clustering and a barrier detection method. A kinship
based spatial autocorrelation showed a contemporary within-lagoon connectivity up
to 20 km. Our findings indicate that strong differentiation or admixtures shaped
historical connectivity and that a pre- and post LGM genetic imprint of R.
cirrhosa along the European coasts was maintained from their occurrence in
primary habitats. Additionally, this study demonstrates the importance of
unraveling thresholds of genetic breaks in combination with ocean dispersal
modeling to infer patterns of connectivity.
PMID- 29951081
TI - Fragile X-Associated Tremor/Ataxia Syndrome: Unmet Needs and a Path for the
Future.
PMID- 29951082
TI - Prediction of Complex Traits: Robust Alternatives to Best Linear Unbiased
Prediction.
AB - A widely used method for prediction of complex traits in animal and plant
breeding is "genomic best linear unbiased prediction" (GBLUP). In a quantitative
genetics setting, BLUP is a linear regression of phenotypes on a pedigree or on a
genomic relationship matrix, depending on the type of input information
available. Normality of the distributions of random effects and of model
residuals is not required for BLUP but a Gaussian assumption is made implicitly.
A potential downside is that Gaussian linear regressions are sensitive to
outliers, genetic or environmental in origin. We present simple (relative to a
fully Bayesian analysis) to implement robust alternatives to BLUP using a linear
model with residual t or Laplace distributions instead of a Gaussian one, and
evaluate the methods with milk yield records on Italian Brown Swiss cattle, grain
yield data in inbred wheat lines, and using three traits measured on accessions
of Arabidopsis thaliana. The methods do not use Markov chain Monte Carlo sampling
and model hyper-parameters, viewed here as regularization "knobs," are tuned via
some cross-validation. Uncertainty of predictions are evaluated by employing
bootstrapping or by random reconstruction of training and testing sets. It was
found (e.g., test-day milk yield in cows, flowering time and FRIGIDA expression
in Arabidopsis) that the best predictions were often those obtained with the
robust methods. The results obtained are encouraging and stimulate further
investigation and generalization.
PMID- 29951083
TI - Kynurenine 3-Monooxygenase Gene Associated With Nicotine Initiation and
Addiction: Analysis of Novel Regulatory Features at 5' and 3'-Regions.
AB - Tobacco smoking is widespread behavior in Qatar and worldwide and is considered
one of the major preventable causes of ill health and death. Nicotine is part of
tobacco smoke that causes numerous health risks and is incredibly addictive; it
binds to the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) in the brain.
Recent studies showed alpha7nAChR involvement in the initiation and addiction of
smoking. Kynurenic acid (KA), a significant tryptophan metabolite, is an
antagonist of alpha7nAChR. Inhibition of kynurenine 3-monooxygenase enzyme
encoded by KMO enhances the KA levels. Modulating KMO gene expression could be a
useful tactic for the treatment of tobacco initiation and dependence. Since KMO
regulation is still poorly understood, we aimed to investigate the 5' and 3'
regulatory factors of KMO gene to advance our knowledge to modulate KMO gene
expression. In this study, bioinformatics methods were used to identify the
regulatory sequences associated with expression of KMO. The displayed
differential expression of KMO mRNA in the same tissue and different tissues
suggested the specific usage of the KMO multiple alternative promoters. Eleven
KMO alternative promoters identified at 5'-regulatory region contain TATA-Box,
lack CpG Island (CGI) and showed dinucleotide base-stacking energy values
specific to transcription factor binding sites (TFBSs). The structural features
of regulatory sequences can influence the transcription process and cell type
specific expression. The uncharacterized LOC105373233 locus coding for non-coding
RNA (ncRNA) located on the reverse strand in a convergent manner at the 3'-side
of KMO locus. The two genes likely expressed by a promoter that lacks TATA-Box
harbor CGI and two TFBSs linked to the bidirectional transcription, the NRF1, and
ZNF14 motifs. We identified two types of microRNA (miR) in the uncharacterized
LOC105373233 ncRNA, which are like hsa-miR-5096 and hsa-miR-1285-3p and can
target the miR recognition element (MRE) in the KMO mRNA. Pairwise sequence
alignment identified 52 nucleotides sequence hosting MRE in the KMO 3' UTR
untranslated region complementary to the ncRNA LOC105373233 sequence. We
speculate that the identified miRs can modulate the KMO expression and together
with alternative promoters at the 5'-regulatory region of KMO might contribute to
the development of novel diagnostic and therapeutic algorithm for tobacco
smoking.
PMID- 29951085
TI - Genetic Differentiation of North-East Argentina Populations Based on 30 Binary X
Chromosome Markers.
AB - Alu insertions, INDELs, and SNPs in the X chromosome can be useful not only for
revealing relationships among populations but also for identification purposes.
We present data of 10 Alu insertions, 5 INDELs, and 15 SNPs of X-chromosome from
three Argentinian north-east cities in order to gain insight into the genetic
diversity of the X chromosome within this region of the country. Data from 198
unrelated individuals belonging to Posadas, Corrientes, and Eldorado cities were
genotyped for Ya5DP62, Yb8DP49, Ya5DP3, Ya5NBC37, Ya5DP77, Ya5NBC491, Ya5DP4,
Ya5DP13, Yb8NBC634, and Yb8NBC102 Alu insertions, for MID193, MID1705, MID3754,
MID3756 and MID1540 Indels and for rs6639398, rs5986751, rs5964206, rs9781645,
rs2209420, rs1299087, rs318173, rs933315, rs1991961, rs4825889, rs1781116,
rs1937193, rs1781104, rs149910, and rs652 SNPs. No deviations from Hardy-Weinberg
equilibrium were observed for Posadas and Corrientes. However, Eldorado showed
significant values, and it was found to have an internal substructuring with two
groups of different origin, one showing higher similarity with European
countries, and the other with more similarities to Posadas and Corrientes. Fst
pairwise genetic distances emerged for some markers among the studied populations
and also between our data and those from other countries and continents. Of
particular interest, Alu insertions demonstrated the most differences, and could
be of use in ancestry studies for these populations, while INDELs and SNPs
variation were informative for differentiation within the country.
PMID- 29951084
TI - Evolutionary Pattern and Large-Scale Architecture of Mutation Networks of 2009 A
(H1N1) Influenza A Virus.
AB - The adaptive evolution of influenza virus is an important question, but
predicting its evolutionary future will be more challenging. Here, we
investigated the mutation characteristic of influenza virus based on the complete
genome data of 2009 (H1N1) influenza A virus. By assuming that evolution proceeds
via the accumulation of mutations, we analyzed the mutation networks at four
different time stages and found that the network structure follows the
characteristics of a scale-free network. These results will be important for
epidemiology and the future control of influenza viruses. Furthermore, we
predicted the predominant mutation virus strain by using the early mutation
network of influenza viruses, and this result was consistent with the WHO
recommendation for the candidate vaccine of influenza virus. The key contribution
of this study is that we explained the biological significance of this scale-free
network for influenza pandemic and provided a potential method for predicting the
candidate vaccine by using the early-stage network.
PMID- 29951086
TI - Microbiome Research Is Becoming the Key to Better Understanding Health and
Nutrition.
AB - The human microbiome has emerged as the crucial moderator in the interactions
between food and our body. It is increasingly recognised that the microbiome can
change our mind and health status, or switch on a wide range of diseases
including cancer, cardio-metabolic diseases, allergies, and obesity. The causes
of diseases are often only partially understood. However, nutrients, metabolites,
and microbes are increasingly regarded as key players, even where the complete
disease mechanisms remain unclear. The key to progress in the future will be to
use and exploit additional, newly emerging disciplines such as metagenomics to
complement patient information and to bring our understanding of diseases and the
interrelation and effects of nutritional molecules to the next level. The EU has
already funded 216 projects under the 7th Framework Programme and Horizon 2020
programmes to promote metagenomics and to advance our knowledge of microbes. This
support started with the catalysing MetaHIT project that has produced a catalogue
of gut microbes, and has arrived now at the very multi-disciplinary SYSCID action
looking at how the microbiome is driving its resilience potential and our health.
Together, these projects involve an investment of more than ?498 M. However, in
Horizon 2020, the new EU Health and Food Work Programmes for 2018-2020 go even
further by setting new goals to find applications and to generate more knowledge
on the microbiome, nutrition, various hosts of microbes, and their relation to
health and disease. The big vision is to modulate health and diseases via the
microbiome and nutrition, while at the same time other factors such as omics,
molecular signatures, and lifestyle are constant. In this way, microbiome and
nutrition research is moving from an isolated and despised offside position to a
beacon of hope with a lot of potential and possibilities.
PMID- 29951087
TI - Synthesis, Structural Analysis, and Biological Activities of Some Imidazolium
Salts.
AB - Four newly synthesized imidazolium salts were characterized by nuclear magnetic
resonance, vibrational spectra, and mass spectra. Then, the density functional
theory calculations were performed to obtain the molecular configurations on
which the theoretical nuclear magnetic resonance and infrared spectra were
consequently obtained. The comparison of calculated spectra with the experimental
spectra for each molecule leads to the conclusion that the theoretical results
can be assumed to be a good approach to their molecular configurations. The in
vitro biological activities of the salts on the selected bacteria and cancer cell
lines were determined by using the broth dilution method according to Clinical
and Laboratory Standards Institute guidelines. The 1,3-bis(2-hydroxyethyl)
imidazolidinium bromide and 3-(2-ethoxy-2-oxoethly)-1-(3-aminopropyl)-1H-imidazol
3-ium bromide showed efficiency on Bacillus cereus ATCC 11778. The 3-bis(2
carboxyethyl)-4-methyl-1-H-imidazol-3-ium bromide was effective on HeLa while a
similar effect was observed on Hep G2 with 3-(2-carboxyethyl)-1-(3-aminopropyl)
1H-imidazol-3-ium bromide.
PMID- 29951088
TI - Hydrothermal Synthesis, Structural Characterization, and Interaction Mechanism
with DNA of Copper(II) Complex Containing 2,2'-Bipyridine.
AB - A Cu(II) complex [Cu(bipy)(H2O)2(SO4)] n (bipy = 2,2'-bipyridine) was synthesized
by hydrothermal method and characterized structurally by elemental analyses,
single crystal X-ray diffraction, infrared spectra, and thermogravimetry and
differential scanning calorimetry. The Cu(II) was hexacoordinated by two N atoms
from bipy, two O atoms from different sulfate radical anions, and two O atoms
from two water molecules, forming a slightly distorted octahedral geometry, and
bridged by sulfato groups into polymeric chains. Under the condition of
physiological pH, the interaction mechanism between the complex and hsDNA was
explored with acridine orange as a fluorescence probe by spectroscopic methods.
The binding modes between the complex and hsDNA were the electrostatic and
embedded modes.
PMID- 29951089
TI - Combining Cryptography with EEG Biometrics.
AB - Cryptographic frameworks depend on key sharing for ensuring security of data.
While the keys in cryptographic frameworks must be correctly reproducible and not
unequivocally connected to the identity of a user, in biometric frameworks this
is different. Joining cryptography techniques with biometrics can solve these
issues. We present a biometric authentication method based on the discrete
logarithm problem and Bose-Chaudhuri-Hocquenghem (BCH) codes, perform its
security analysis, and demonstrate its security characteristics. We evaluate a
biometric cryptosystem using our own dataset of electroencephalography (EEG) data
collected from 42 subjects. The experimental results show that the described
biometric user authentication system is effective, achieving an Equal Error Rate
(ERR) of 0.024.
PMID- 29951090
TI - Newly Generated Cells in the Dentate Gyrus Differentially Respond to Brief
Spatial Exploration and Forced Swim in Adult Female Balb/C Mice.
AB - Neurogenesis in the hippocampus is influenced by several factors including
external stimuli. In addition to their involvement in learning and memory
processes, newborn neurons of the dentate gyrus (DG) buffer against the effects
of stress. Although the response of these cells to environmental stimuli has been
shown, the age of the cells that respond to a brief spatial exploration or a
stressful situation produced by forced-swim stress in adult female Balb/C mice is
still unknown. Here, we investigated the activation of newborn neurons after
three (IdU) or six weeks (CldU) postlabelling with the expression of Arc in the
same mice but exposed to different environmental stimuli. Mice housed in standard
conditions showed an increase in the activation of CldU-labelled cells after two
exposures to a brief spatial exploration but no increase in the activation of IdU
labelled cells compared with the control group. Additionally, we analysed
neuronal activation in the DG of mice housed in standard conditions and further
exposed to forced-swim stress. We found a decreased activation of IdU-labelled
cells in mice exposed to forced-swim stress with increase number of CldU-labelled
cells. Our results suggest that based on their time postlabelling, newly
generated hippocampal neurons show a different response to several environmental
stimuli.
PMID- 29951091
TI - Hidradenitis Suppurativa in Kuala Lumpur, Malaysia: A 7-Year Retrospective
Review.
AB - Introduction: Hidradenitis Suppurativa (HS) is a chronic inflammatory skin
condition characterized by inflamed nodules, abscesses, sinus tracts, and
scarring, which can occur in any skin containing folliculopilosebaceous units. We
aim to identify the demographic and clinical characteristics and treatment
modalities in patients with HS. Methods: A retrospective analysis involving
records of patients diagnosed with HS in Hospital Kuala Lumpur from July 2009 to
June 2016. Results: Sixty-two patients were identified, with equal cases
involving males and females. Majority of patients were Malays (41.9%), followed
by Indians (35.5%), Chinese (17.7%), and other ethnicities (4.8%). Median age at
diagnosis was 25 (IQR: 14) years. There is a delay in diagnosis with a median of
24 (IQR: 52) months. Most of the patients had lesions on the axilla (85.5%),
followed by groin (33.9%) and gluteal region (29%). Gluteal lesions were more
common in males. Nodules (67.7%), sinuses (56.5%), and abscesses (33.9%) were the
main clinical features, with 43.5% classified under Hurley stage 2. There was no
difference in terms of symptoms and types of lesions among different ethnicities
and genders. Majority received systemic antibiotics, more than half had retinoid,
and third of the patients had surgical intervention. Conclusions: A prompt
recognition of HS is imperative, to screen for comorbidities and to initiate
early treatment to reduce physical and psychological complications.
PMID- 29951092
TI - Comparison of the Morphological and Physical Properties of Different Absorbent
Wound Dressings.
AB - Good quality wound dressings should have exceptional properties for usage, such
as being able to remove excess wound exudates, having rapid dehydration, and
providing optimal water vapour permeability. This study evaluated and compared
the morphological and physical properties of six different commercially absorbent
wound dressings in Thailand: two hydrocolloids, two alginates, and two foams.
These wound dressings are available in a variety of components and structures,
some of which have a multilayer structure. The results showed that the calcium
sodium alginate dressings had better absorption properties than the calcium
alginate dressings, hydrocolloid dressings, hydrocolloid with foam layer
dressings, foam with polyurethane film layer dressings, and foam with hydrogel
and polyurethane film layer dressings. Furthermore, the calcium sodium alginate
dressings had the highest rate of dehydration and provided an optimal water
vapour transmission rate. However, the calcium sodium alginate dressings could
not retain the original structure after being submerged with a wound exudate.
PMID- 29951093
TI - Clinicopathological and Survival Outcomes of Well-Differentiated Thyroid
Carcinoma Undergoing Dedifferentiation: A Retrospective Study from FUSCC.
AB - Background: Recently, several studies have reported that dedifferentiation occurs
in fatal well-differentiated thyroid cancer (WDTC) cases. This study aimed at
investigating the clinicopathological characteristics of WDTC undergoing
dedifferentiation. Methods: A total of 63 WDTC patients harboring
dedifferentiated phenotype were enrolled in the study. The Kaplan-Meier method
and Cox regression analysis were used to perform survival analyses. Harrell index
of concordance (C-index) and Akaike information criterion (AIC) were calculated
to compare the predictive value for prognosis among several prognostic
classification systems. Results: The median cause-specific survival (CSS) of
patients was 138 months, with the CSS rate of 64.0% and 53.3% at 5 and 10 years,
respectively. Presence of the anaplastic thyroid cancer (ATC) phenotype
significantly increased the risk of poor CSS (P = 0.033), and age was the only
independent risk factor for disease progression (P = 0.015). The C-index and AIC
of the age, grade, extent, size (AGES) prognostic classification system for the
CSS were 0.723 and 59.937, respectively. Conclusions: The presence of
dedifferentiated phenotypes can be responsible for the poor outcomes in WDTC
patients. The AGES system demonstrates to be an optimal prognostic system for
WDTC undergoing dedifferentiation.
PMID- 29951095
TI - Corrigendum to "Biological Effects of Medicinal Plants on Induced Periodontitis:
A Systematic Review".
AB - [This corrects the article DOI: 10.1155/2016/3719879.].
PMID- 29951094
TI - Early Childhood Caries: Epidemiology, Aetiology, and Prevention.
AB - Early childhood caries (ECC) is one of the most prevalent diseases in children
worldwide. ECC is driven by a dysbiotic state of oral microorganisms mainly
caused by a sugar-rich diet. Additionally, poor oral hygiene or insufficient
dental plaque removal leads to the rapid progression of ECC. ECC leads not only
to dental destruction and pain with children, but also affects the quality of
life of the caregivers. Children with extensive ECC are at high risk to develop
caries with the permanent dentition or will have other problems with speaking
and/or eating. To prevent ECC, several strategies should be taken into account.
Children should brush their teeth with toothpastes containing gentle ingredients,
such as mild surfactants and agents showing antiadherent properties regarding
oral microorganisms. Parents/caregivers have to help their children with brushing
the teeth. Furthermore, remineralizing and nontoxic agents should be included
into the toothpaste formulation. Two promising biomimetic agents for children's
oral care are amorphous calcium phosphate [Ca x (PO4) yn H2O] and hydroxyapatite
[Ca5(PO4)3(OH)].
PMID- 29951096
TI - Conformational and Functional Properties of Soybean Proteins Produced by
Extrusion-Hydrolysis Approach.
AB - The conformational and functional changes of soybean protein after a hybrid
extrusion-hydrolysis method were evaluated. Three extrusion temperatures (60, 80,
and 100 degrees C) were used prior to enzymatic hydrolysis. The hydrolysis
degrees, molecular weight profiles, solubilities, surface hydrophobicities,
sulphydryl contents, disulfide bound, water holding capacity, emulsion, and foam
properties of the protein isolated from the enzyme-hydrolyzed extruded soybeans
were analyzed. It shows that extrusion caused significant changes in the
hydrophobicity, molecular weight distribution, solubility, surface
hydrophobicity, emulsification activity, and stability of the protein. The
increase of molecular weights could be attributed to the formation of protein
aggregates during extrusion. Extrusion and enzymatic hydrolysis led to a sharp
increase in the number of disulfide bonds with a decrease of the sulphydryl
group. The water holding capacity and the solubility of protein increased with
the increase of extrusion temperature and hydrolysis time. Extrusion improved the
emulsifying activity but reduced the emulsifying stability of the recovered
proteins. Extrusion improved the foam capacity but reduced the foam stability of
the proteins. The data demonstrated that the extrusion-hydrolysis treatment
significantly altered the conformational and functional properties of soybean
protein, which may be further optimized for the development of new soy protein
ingredient with desired functional properties.
PMID- 29951097
TI - Genomic Variability among Field Isolates and Laboratory-Adapted Strains of
Leptospira borgpetersenii Serovar Hardjo.
AB - Leptospira borgpetersenii serovar Hardjo colonizes cattle kidneys and may
occasionally infect humans and other mammals. Strains belonging to two clonal
subtypes (types A and B) with marked differences in their pathogenicity in the
hamster experimental model have been described for this serovar. Such differences
have been attributed to point mutations in individual genes, although those genes
have not yet been characterized. In order to better understand genetic
variability among L. borgpetersenii serovar Hardjo isolates, we sequenced and
compared the genomes of two laboratory-adapted strains and three abattoir-derived
field isolates of L. borgpetersenii serovar Hardjo. Relatively low genetic
variability was observed within isolates of the same subtype, with most of the
mutations of moderate or high impact found in the laboratory-adapted isolates. In
contrast, several differences regarding gene content and genetic variants were
observed between the two subtypes. Putative type-specific genes appear to encode
proteins associated with functions that are critical for infection. Some of these
genes seem to be involved in transcriptional regulation, possibly leading to a
distinct regulatory pattern in each type. These results show that changes in
regulatory mechanisms, previously suggested to be critical during Leptospira
speciation, may occur in L. borgpetersenii. In addition, the bioinformatics
methodology used in this study for variant calling can be useful to other groups
working with nonmodel prokaryotic organisms such as Leptospira species.
PMID- 29951098
TI - Randomized Clinical Trial Comparing Bucket Handle and Cartilage Tympanoplasty
Techniques for the Reconstruction of Subtotal or Anterior Tympanic Membrane
Perforation.
AB - Objective: The purpose of the study is to compare the clinical outcome of the two
techniques of Bucket Handle Tympanoplasty and Cartilage Tympanoplasty in
achieving success in graft survival as well as acceptable auditory results. 60
patients who suffered chronic otitis media with anterior perforation of the
tympanic membrane were chosen. The patients were randomly assigned using Block
Randomization Method of two groups including patients who underwent Bucket Handle
Tympanoplasty (n = 30) or those that underwent Cartilage Tympanoplasty (n = 30).
The patients were followed up for 1, 3, 6, and 12 months postoperatively.
Results: The mean PTA was lower in Bucket Handle Tympanoplasty group as case
group compared to Cartilage Tympanoplasty group as the control (P = 0.023). No
significant statistical differences had identified passing through the time, in
terms of PTA outcome (P Value = 0.547) and SRT outcome (P Value = 0.352), between
Bucket Handle Tympanoplasty group and the Cartilage Tympanoplasty group. In
total, postoperative tympanic membrane perforation was found in 10.0% of patients
in Cartilage Tympanoplasty group and 13.3% in Bucket Handle Tympanoplasty group
with no difference (P = 0.500). Conclusions: Hearing improvements in both methods
were similar. Registration Number: The trial is registered with
IRCT2016022626773N1.
PMID- 29951099
TI - The Role of Mannose-Binding Lectin Serum Level in Tubotympanic Chronic
Suppurative Otitis Media.
AB - Background: Chronic suppurative otitis media (CSOM) is a common public health
problem worldwide and a major cause of hearing impairment especially in
developing countries. The role of Mannose-Binding Lectin (MBL), a component of
innate immunity, in CSOM has not been studied. The aim of the study was to
examine whether MBL deficiency was more frequently present in cases group of
tubotympanic CSOM patients rather than healthy subjects. Material and Methods:
This was an analytic observational study. Subjects were enrolled in the
Otorhinolaryngology Clinic at Margono Soekarjo Hospital, Purwokerto, Indonesia.
An independent t-test was used to compare the mean of MBL serum concentration
between tubotympanic CSOM subjects and control. Results: From 36 tubotympanic
CSOM patients, there were 8 (22.22%) patients with MBL deficiency (MBL level <
100 ng/ml), while no deficiency was found in the control group. The mean of MBL
level in cases group was 354.88 ng/ml, with the lowest level being 0.001 ng/ml
and the highest level 690.24 ng/ml, while in the control group MBL level mean was
376.27 with the lowest level being 188.71 and the highest level 794.54 ng/ml.
Conclusion: There was no significant difference of MBL serum level between
tubotympanic CSOM and control group. However, the presence of subjects with MBL
deficiency in the tubotympanic CSOM group might be considered as playing a role
in the tubotympanic CSOM.
PMID- 29951100
TI - Efficiency of Cell Therapy to GC-Induced ONFH: BMSCs with Dkk-1 Interference Is
Not Superior to Unmodified BMSCs.
AB - Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a hip
disorder, and it threatens patients who require megadose of steroid therapies.
Nowadays, no valid therapies can reverse the development of GC-induced ONFH once
it occurs. Stem cell therapy to GC-induced ONFH would be a promising choice.
Although the pathogenesis of GC-induced ONFH is not yet fully clear, Dickkopf-1
(Dkk-1) upregulated by excessive GC use, which hinders the canonical Wnt pathway,
could be an explanation. Thus, the aim of the present work lies in investigating
the efficiency of the allograft bone marrow stem cells (BMSCs) with Dkk-1
interference in preventing the progression of the GC-induced ONFH. Lentivirus
meditated Dkk-1 RNAi was introduced into BMSCs which was exposed to dexamethasone
(10-6 mol/L) in vitro. This interference blocked Dkk-1 overexpression by GC and
afterwards prompted the transduction of Wnt/beta-catenin in which the Runx2 and
PPARgamma were upregulated and downregulated, respectively. Thus, the
osteogenesis was promoted while adipogenesis was inhibited. In vivo, GC-induced
ONFH rats were treated by allotransplantation of BMSCs with Dkk-1 interference,
and the progression of the disease was prevented. However, the effects were not
significantly superior to treatment with nongenetically modified or normal BMSCs.
PMID- 29951101
TI - Quality Assessment of Some Essential Children's Medicines Sold in Licensed
Outlets in Ashanti Region, Ghana.
AB - The quality of 68 samples of 15 different essential children's medicines sold in
licensed medicine outlets in the Ashanti Region, Ghana, was evaluated. Thirty-two
(47.1%) of the medicines were imported, mainly from India (65.6%) and the United
Kingdom (28.1%), while 36 (52.9%) were locally manufactured. The quality of the
medicines was assessed using content of active pharmaceutical ingredient (API),
pH, and microbial limit tests, and the results were compared with pharmacopoeial
standards. Twenty-six (38.2%) of the samples studied passed the official content
of API test while 42 (61.8%) failed. Forty-nine (72.1%) of the samples were
compliant with official specifications for pH while 19 (27.9%) were noncompliant.
Sixty-six (97.1%) samples passed the microbial load and content test while 2
(2.9%) failed. Eighteen (26.5%) samples passed all the three quality evaluation
tests, while one (1.5%) sample (CFX1) failed all the tests. All the amoxicillin
suspensions tested passed the three evaluation tests. All the ciprofloxacin,
cotrimoxazole, flucloxacillin, artemether-lumefantrine, multivitamin, and folic
acid samples failed the content of API test and are substandard. The overall API
failure rate for imported products (59.4%) was comparable to locally manufactured
(63.9%) samples. The results highlight the poor quality of the children's
medicines studied and underscore the need for regular pharmacovigilance and
surveillance systems to fight this menace.
PMID- 29951102
TI - Neurocysticercosis in Children with Seizures: A Cross-Sectional Study.
AB - Background: Neurocysticercosis (NCC), a common cause of seizures in children from
low and middle income countries (LMICs), if not diagnosed and treated early
enough may lead to considerable morbidity and mortality. There is a lack of data
on the prevalence of NCC and its clinical characteristics among those with
seizure in South-Western Nepal. Aims and Objectives: To study the prevalence and
clinical characteristics of NCC in children with seizures. Material and Methods:
All children admitted to Universal College of Medical Sciences, a tertiary
hospital in South-Western Nepal with seizures during 2014-16, were tested for
NCC. NCC was diagnosed by neuroimaging [computerized tomography (CT) scan or
magnetic resonance imaging (MRI)]. We used logistic regression to test the
association between NCC with participants' characteristics and clinical symptoms.
Results: Among 4962 in-patient children, 168 (104 boys and 64 girls) had seizures
(138 with generalized tonic clonic seizures (GTCS) and 30 with focal seizures).
43% of children with seizures had CT scan confirmed NCC. The prevalence of NCC in
the oldest children (13-16 years) was significantly greater (57.1% versus 15.6%)
compared to the youngest (0-4 years) one (p < 0.001). Among 72 children with NCC,
the proportions of children with vesicular, calcified, and colloidal stages were
76% (n = 35), 18% (n = 13), and 6% (n = 2), respectively. Children with focal
seizures had 13% more NCC compared to those with GTCS but the result was
statistically not significant. The adjusted odds of having NCC among 5-8 years, 9
12 years, and 13-16 years children were 6.6 (1.78-24.60), 11.06 (2.74-44.60), and
14.47 (3.13-66.96), respectively, compared to 0-4-year-old children. Reoccurrence
of seizures within the first 3 months of taking antiepileptic drug in those with
NCC was approximately 3 times higher compared to those without NCC (11% versus
4%, p = 0.084). Conclusions: This study shows that NCC contributes significantly
to higher prevalence of seizures in children in South-Western region of Nepal.
PMID- 29951103
TI - Satisfaction with Delivery Services Offered under the Free Maternal Healthcare
Policy in Kenyan Public Health Facilities.
AB - Background: Patients' satisfaction is an individual's positive assessment
regarding a distinct dimension of healthcare and the perception about the quality
of services offered in that health facility. Patients who are not satisfied with
healthcare services in a certain health facility will bypass the facility and are
unlikely to seek treatment in that facility. Objective: To determine satisfaction
level of mothers with the free maternal services in selected Kenyan public health
facilities after the implementation of the free maternal healthcare policy.
Methods: Data was collected through a quantitative exit survey questionnaire. The
respondents were mothers who had delivered in the health facilities and were
waiting to leave the health facilities after discharge. The sample included 2,216
mothers in 77 public health facilities across 14 counties in Kenya under tier 3
and tier 4 categories. The number of respondents to be interviewed was
proportionately arrived at based on each health facility's bed capacity. Results:
The study established a satisfaction rate of 54.5% among the beneficiaries of the
free maternal healthcare services in the country. Mothers benefiting from the
free delivery services were satisfied with communication by the healthcare
workers, staff availability in the delivery rooms, availability of staff in the
wards, and drug and supplies availability (>56%) but unsatisfied with
consultation time, cleanliness, and privacy in the wards (<56%). High education
levels and lengthy stay in healthcare facilities were negatively associated with
the satisfaction with the free delivery services (P < 0.05). Conclusion: There is
a high satisfaction with the free maternal healthcare services in Kenya. However,
the implementation of the free maternal healthcare policy was associated with low
privacy, poor hygiene, and low consultation time in the health facilities.
Therefore there is need to address these service gaps so as to attract more
mothers to deliver in public health facilities.
PMID- 29951104
TI - Pulse Wave Cycle Features Analysis of Different Blood Pressure Grades in the
Elderly.
AB - Background and Objective: The same range of blood pressure values may reflect
different vascular functions, especially in the elderly. Therefore, a single
blood pressure value may not comprehensively reveal cardiovascular function. This
study focused on identifying pulse wave features in the elderly that can be used
to show functional differences when blood pressure values are in the same range.
Methods: First, pulse data were preprocessed and pulse cycles were segmented.
Second, time domain, higher-order statistics, and energy features of wavelet
packet decomposition coefficients were extracted. Finally, useful pulse wave
features were evaluated using a feature selection and classifier design. Results:
A total of 6,075 pulse wave cycles were grouped into 3 types according to
different blood pressure levels and each group was divided into 2 categories
according to a history of hypertension. The classification accuracy of feature
selection in the 3 groups was 97.91%, 95.24%, and 92.28%, respectively.
Conclusion: Selected features could be appropriately used to analyze
cardiovascular function in the elderly and can serve as the basis for research on
a cardiovascular risk assessment model based on Traditional Chinese Medicine
pulse diagnosis.
PMID- 29951105
TI - Structural Changes Induced by Acupuncture in the Recovering Brain after Ischemic
Stroke.
AB - The aim of this study was to observe the grey matter (GM) tissue changes of
ischemic stroke patients, to explore the therapy responses and possible mechanism
of acupuncture. 21 stroke patients were randomly assigned to receive either
acupuncture plus conventional (Group A) or only conventional (Group B) treatments
for 4 weeks. All patients in both groups accepted resting-state functional
magnetic resonance (fMRI) scan before and after treatment, and the voxel-based
morphometry (VBM) analysis was performed to detect the cerebral grey structure
changes. The modified Barthel index (MBI) was used to evaluate the therapeutic
effect. Compared with the patients in Group B, the patients in Group A exhibited
a more significant enhancement of the changes degree of MBI from pre- to post
treatment intervention. VBM analyses found that after treatment the patients in
Group A showed extensive changes in GMV. In Group A, the left frontal lobe,
precentral gyrus, superior parietal gyrus, anterior cingulate cortex, and middle
temporal gyrus significantly increased, and the right frontal gyrus, inferior
parietal gyrus, and middle cingulate cortex decreased (P < 0.05, corrected). In
addition, left anterior cingulate cortex and left middle temporal gyrus are
positively related to the increase in MBI score (P < 0.05, corrected). In Group
B, right precentral gyrus and right inferior frontal gyrus increased (P < 0.05,
corrected). In conclusion, acupuncture can evoke pronounced structural
reorganization in the frontal areas and the network of DMN areas, which may be
the potential therapy target and the potential mechanism where acupuncture
improved the motor and cognition recovery.
PMID- 29951106
TI - Therapeutic Effects of Kangzhi Syrup in a Guinea Pig Model of Ovalbumin-Induced
Cough Variant Asthma.
AB - Purpose: This study aimed to investigate the possible effects and underlying
mechanisms of Kangzhi syrup on ovalbumin- (OVA-) induced cough variant asthma
(CVA) in guinea pigs. Methods: All 48 guinea pigs were randomly assigned to four
experimental groups: normal, OVA model with or without Kangzhi syrup (OVA and OVA
+ KZ), and OVA with Dexamethasone (OVA + DM). After sensitizing the guinea pigs,
a cough challenge was performed by the inhalation of capsaicin. The antitussive
effect, inflammatory cells, cytokines in bronchoalveolar lavage fluid (BALF) and
lung tissue, and morphological changes were examined. Results: Compared with
model group, Kangzhi syrup effectively exerted an antitussive effect (p < 0.0001)
and reduced the pneumonic anaphylacticitis by inhibiting the infiltration of
total inflammatory cells (p < 0.0001) and reducing the percentage of eosinophil
in BALF (p < 0.0001). Moreover, evidence from morphological studies also
demonstrated that Kangzhi syrup inhibited the infiltration of inflammatory cells
and ameliorated the structure changes. NF-kappaB and TGF-beta1 expression were
attenuated in the OVA + KZ group versus the OVA group (p < 0.0001). Additionally,
a semiquantitative analysis of TGF-beta1 expression also demonstrated that the
Kangzhi syrup attenuated this profibrogenic growth factor (p < 0.001).
Conclusions: The results demonstrated that Kangzhi syrup exerted a considerable
antitussive effect in CVA animal model, which depended on its marked impact on
the anti-anaphylactic inflammation. Additionally, it could ameliorate the airway
remodeling by inhibiting NF-kappaB and TGF-beta1 signal pathway.
PMID- 29951107
TI - Total Flavonoids from Radix Glycyrrhiza Exert Anti-Inflammatory and
Antitumorigenic Effects by Inactivating iNOS Signaling Pathways.
AB - Inducible nitric oxide synthase (iNOS) plays an important role in inflammation,
which has also been considered as a major driver of breast cancer disease
progression. Radix Glycyrrhiza (RG) has been broadly used for its anti
inflammatory and antitumorigenic effects. However, the mechanisms of regulation
of iNOS in inflammation and cancer have not been fully explored. Total flavonoids
isolated from RG (TFRG) exhibited anti-inflammatory activity through the
regulation of ERK/NF-kappaB/miR-155 signaling and suppression of iNOS expression
in LPS/IFN-gamma stimulated RAW264.7 macrophages without cytotoxicity. TFRG also
markedly reduced tumor mass of breast cancer cell MDA-MB-231 xenografts with
suppression of iNOS expression, formation of 3-nitrotyrosine (3-NT), and
inactivation of protumorigenic JAK2/STAT3 signaling pathway. These results
suggested that TFRG limited the development of breast cancer and inflammation due
to its property of iNOS inhibition.
PMID- 29951108
TI - Anti-obesity and Hypolipidemic effects of garlic oil and onion oil in rats fed a
high-fat diet.
AB - Background: Until now, little research concerning the lipid-lowering and anti
obesity functions of garlic oil and onion oil has been performed. The objective
of this study was to explore the effects of garlic oil and onion oil on serum
lipid levels in hyperlipidemia model rats, to provide a scientific basis for the
prevention of hyperlipidemia through a dietary approach, and to explore the
potential health benefits of garlic and onion. Method: Ninety-six male Sprague
Dawley rats were randomly allocated into eight groups based on their body weight
and serum levels of triglycerides (TG) and total cholesterol (TC). The rats
received repeated oral administration of volatile oils extracted from garlic and
onion for 60 days. Serum lipids and parameters of obesity were examined. Results:
The volatile oils suppressed the HFD-induced body weight gain and tended to
decrease adipose tissue weight. The oils decreased the levels of TG, TC and LDL-C
and increased the serum level of HDL-C compared with the rats in the
hyperlipidemia model groups (P < 0.05). The oils were also effective at improving
the lipid profile and alleviating hepatic steatosis. Conclusion: Our results
implied that garlic oil and onion oil have anti-obesity properties that can
counteract the effects of an HFD on body weight, adipose tissue weight, and serum
lipid profiles.
PMID- 29951110
TI - Correction to: The property of the Japanese version of the Recovery Knowledge
Inventory (RKI) among mental health service providers: a cross sectional study.
AB - [This corrects the article DOI: 10.1186/s13033-017-0178-7.].
PMID- 29951109
TI - MET-values of standardised activities in relation to body fat: studies in
pregnant and non-pregnant women.
AB - Background: Physical activity is associated with health in women. Published MET
values (MET: metabolic equivalent of task) may assess physical activity and
energy expenditure but tend to be too low for subjects with a high total body fat
(TBF) content and therefore inappropriate for many contemporary women. The MET
value for an activity is the energy expenditure of a subject performing this
activity divided by his/her resting energy expenditure, often assumed to be 4.2
kJ/kg/h. Relationships between TBF and MET have been little studied although
overweight and obesity is common in women. Available data indicate that MET
values decrease during pregnancy but more studies in pregnant contemporary women
are needed. Subjects and methods: Using indirect calorimetry we measured energy
expenditure and assessed MET-values in women, 22 non-pregnant (BMI: 18-34) and 22
in gestational week 32 (non-pregnant BMI: 18-32) when resting, sitting, cycling
(30 and 60 watts), walking (3.2 and 5.6 km/h) and running (8 km/h). Relationships
between TBF and MET-values were investigated and used to predict modified MET
values. The potential of such values to improve calculations of total energy
expenditure of women was investigated. Results: The resting energy expenditure
was below 4.2 kJ/kg/h in both groups of women. Women in gestational week 32 had a
higher resting energy metabolism (p < 0.001) and 7-15% lower MET-values (p <
0.05) than non-pregnant women. MET-values of all activities were correlated with
TBF (p < 0.05) in non-pregnant women and modified MET-values improved estimates
of total energy expenditure in such women. In pregnant women, correlations (p <=
0.03) between TBF and MET were found for running (8 km/h) and for walking at 5.6
km/h. Conclusions: Our results are relevant when attempts are made to modify the
MET-system in contemporary pregnant and non-pregnant women. MET-values were
decreased in gestational week 32, mainly due to an increased resting energy
metabolism and studies describing how body composition affects the one MET-value
(i.e. the resting energy metabolism in kJ/kg/h) during pregnancy are warranted.
Studies of how pregnancy and TBF affect MET-values of high intensity activities
are also needed. Corrections based on TBF may have a potential to improve the MET
system in non-pregnant women.
PMID- 29951111
TI - Improved biodegradability of hardly-decomposable wastewaters from petrochemical
industry through photo-Fenton method and determination of optimum operational
conditions by response surface methodology.
AB - Background: Petrochemical wastewaters are highly polluting due to having various
destructive materials such as aromatic hydrocarbons and heavy metal ions.
Therefore, they need to be treated before disposal to the environment. However,
due to low biodegradability, applying common treatment methods such as activated
sludge is not feasible for these wastewaters. Methods: Photo-Fenton is an
advanced oxidation process which was applied to promote the biodegradability of
hardly-decomposable petrochemical wastewaters. The wastewater samples were
provided by Maroon and Karoon petrochemical plants, located in Mahshahr, Iran. To
design the experiments and analyze the experimental results, response surface
method with four variables (input COD and TDS concentrations and injected a
dosage of H2O2 and Fe2+) and four fixed parameters (temperature, pH, retention
time, and UV power) were used. Results: The ranges of input COD, H2O2, Fe2+ and
TDS were 1000 to 2500 mg L- 1, 1000 to 4000 mg L- 1, 500 to 3000 mg L- 1, and
4500 to 11,500 mg L- 1, respectively. Average input BOD5/COD ratio was 0.09.
These ranges and values were determined according to the quality of the raw
wastewater and experimental design. Output BOD5/COD ratio was varying between 0.3
and 0.6, which declined with an increase of input COD. The results showed that
the biodegradability of the industrial wastewater was promoted upon application
of higher H2O2 and Fe2+ concentrations. Meanwhile, TDS concentration had no
significant effect on biodegradability of this wastewater. The following optimum
conditions were resulted by evaluating the maximum efficiency of the reactor in
enhancing the biodegradability of the wastewater: 1000 mg L- 1 input COD, 2668 mg
L- 1 H2O2, 1655 mg L- 1 Fe2+, 8000 mg L- 1 TDS, 0.6 output BOD5/COD, 852 mg L- 1
output BOD5 and 939 mg L- 1 output COD. Conclusion: Photo-Fenton method is highly
efficient for increasing the biodegradability of petrochemical wastewaters before
applying biological wastewater treatment.
PMID- 29951112
TI - C-Arm Image-Based Surgical Path Planning Method for Distal Locking of
Intramedullary Nails.
AB - Due to the curvature of the bone marrow cavity, the intramedullary nail used in
long bone fracture fixation can be deformed, causing displacement of the locking
holes. In this study, an algorithm using only one C-arm image to determine the
center positions and axial directions of locking holes was developed for drilling
guidance. Based on conventional method that the axial direction of locking hole
would be identified when locking hole contour is presented as a circle, the
proposed method can locate the circle contour centroid by using one C-arm image
including two elliptical contours. Then the two distal locking holes' axial
direction and centers would be determined. Three experiments were conducted to
verify the performance of the proposed algorithm, which are (1) computer
simulation, (2) use of real intramedullary nails, and (3) actual drilling test
with the bone model. The experimental results showed that the average error of
the axial direction and center position were 0.62 +/- 0.6 degrees , 0.73 +/- 0.53
mm (simulation) and 3.16 +/- 1.36 degrees , 1.10 +/- 0.50 mm (actual nail),
respectively. The last ten drilling test sets were completed successfully (with
an average duration of 48 seconds). Based on the experimental results, the
proposed algorithm was feasible for clinic applications.
PMID- 29951113
TI - Characterization of Bathyarchaeota genomes assembled from metagenomes of biofilms
residing in mesophilic and thermophilic biogas reactors.
AB - Background: Previous studies on the Miscellaneous Crenarchaeota Group, recently
assigned to the novel archaeal phylum Bathyarchaeota, reported on the dominance
of these Archaea within the anaerobic carbohydrate cycle performed by the deep
marine biosphere. For the first time, members of this phylum were identified also
in mesophilic and thermophilic biogas-forming biofilms and characterized in
detail. Results: Metagenome shotgun libraries of biofilm microbiomes were
sequenced using the Illumina MiSeq system. Taxonomic classification revealed that
between 0.1 and 2% of all classified sequences were assigned to Bathyarchaeota.
Individual metagenome assemblies followed by genome binning resulted in the
reconstruction of five metagenome-assembled genomes (MAGs) of Bathyarchaeota.
MAGs were estimated to be 65-92% complete, ranging in their genome sizes from 1.1
to 2.0 Mb. Phylogenetic classification based on core gene sets confirmed their
placement within the phylum Bathyarchaeota clustering as a separate group
diverging from most of the recently known Bathyarchaeota clusters. The genetic
repertoire of these MAGs indicated an energy metabolism based on carbohydrate and
amino acid fermentation featuring the potential for extracellular hydrolysis of
cellulose, cellobiose as well as proteins. In addition, corresponding transporter
systems were identified. Furthermore, genes encoding enzymes for the utilization
of carbon monoxide and/or carbon dioxide via the Wood-Ljungdahl pathway were
detected. Conclusions: For the members of Bathyarchaeota detected in the biofilm
microbiomes, a hydrolytic lifestyle is proposed. This is the first study
indicating that Bathyarchaeota members contribute presumably to hydrolysis and
subsequent fermentation of organic substrates within biotechnological biogas
production processes.
PMID- 29951114
TI - Revealing the transcriptomic complexity of switchgrass by PacBio long-read
sequencing.
AB - Background: Switchgrass (Panicum virgatum L.) is an important bioenergy crop
widely used for lignocellulosic research. While extensive transcriptomic analyses
have been conducted on this species using short read-based sequencing techniques,
very little has been reliably derived regarding alternatively spliced (AS)
transcripts. Results: We present an analysis of transcriptomes of six switchgrass
tissue types pooled together, sequenced using Pacific Biosciences (PacBio) single
molecular long-read technology. Our analysis identified 105,419 unique
transcripts covering 43,570 known genes and 8795 previously unknown genes. 45,168
are novel transcripts of known genes. A total of 60,096 AS transcripts are
identified, 45,628 being novel. We have also predicted 1549 transcripts of genes
involved in cell wall construction and remodeling, 639 being novel transcripts of
known cell wall genes. Most of the predicted transcripts are validated against
Illumina-based short reads. Specifically, 96% of the splice junction sites in all
the unique transcripts are validated by at least five Illumina reads. Comparisons
between genes derived from our identified transcripts and the current genome
annotation revealed that among the gene set predicted by both analyses, 16,640
have different exon-intron structures. Conclusions: Overall, substantial amount
of new information is derived from the PacBio RNA data regarding both the
transcriptome and the genome of switchgrass.
PMID- 29951115
TI - The impact of silicon on cell wall composition and enzymatic saccharification of
Brachypodium distachyon.
AB - Background: Plants and in particular grasses benefit from a high uptake of
silicon (Si) which improves their growth and productivity by alleviating adverse
effects of biotic and abiotic stress. However, the silicon present in plant
tissues may have a negative impact on the processing and degradation of
lignocellulosic biomass. Solutions to reduce the silicon content either by
biomass engineering or development of downstream separation methods are therefore
targeted. Different cell wall components have been proposed to interact with the
silica pool in plant shoots, but the understanding of the underlying processes is
still limited. Results: In the present study, we have characterized silicon
deposition and cell wall composition in Brachypodium distachyon wild-type and low
silicon 1 (Bdlsi1-1) mutant plants. Our analyses included different organs and
plant developmental stages. In the mutant defective in silicon uptake, low
silicon availability favoured deposition of this element in the amorphous form or
bound to cell wall polymers rather than as silicified structures. Several
alterations in non-cellulosic polysaccharides and lignin were recorded in the
mutant plants, indicating differences in the types of linkages and in the three
dimensional organization of the cell wall network. Enzymatic saccharification
assays showed that straw from mutant plants was marginally more degradable
following a 190 degrees C hydrothermal pretreatment, while there were no
differences without or after a 120 degrees C hydrothermal pretreatment.
Conclusions: We conclude that silicon affects the composition of plant cell
walls, mostly by altering linkages of non-cellulosic polymers and lignin. The
modifications of the cell wall network and the reduced silicon concentration
appear to have little or no implications on biomass recalcitrance to enzymatic
saccharification.
PMID- 29951116
TI - Genome editing of Ralstonia eutropha using an electroporation-based CRISPR-Cas9
technique.
AB - Background: Ralstonia eutropha is an important bacterium for the study of
polyhydroxyalkanoates (PHAs) synthesis and CO2 fixation, which makes it a
potential strain for industrial PHA production and attractive host for CO2
conversion. Although the bacterium is not recalcitrant to genetic manipulation,
current methods for genome editing based on group II introns or single crossover
integration of a suicide plasmid are inefficient and time-consuming, which limits
the genetic engineering of this organism. Thus, developing an efficient and
convenient method for R. eutropha genome editing is imperative. Results: An
efficient genome editing method for R. eutropha was developed using an
electroporation-based CRISPR-Cas9 technique. In our study, the electroporation
efficiency of R. eutropha was found to be limited by its restriction-modification
(RM) systems. By searching the putative RM systems in R. eutropha H16 using
REBASE database and comparing with that in E. coli MG1655, five putative
restriction endonuclease genes which are related to the RM systems in R. eutropha
were predicated and disrupted. It was found that deletion of H16_A0006 and
H16_A0008-9 increased the electroporation efficiency 1658 and 4 times,
respectively. Fructose was found to reduce the leaky expression of the arabinose
inducible pBAD promoter, which was used to optimize the expression of cas9,
enabling genome editing via homologous recombination based on CRISPR-Cas9 in R.
eutropha. A total of five genes were edited with efficiencies ranging from 78.3
to 100%. The CRISPR-Cpf1 system and the non-homologous end joining mechanism were
also investigated, but failed to yield edited strains. Conclusions: We present
the first genome editing method for R. eutropha using an electroporation-based
CRISPR-Cas9 approach, which significantly increased the efficiency and decreased
time to manipulate this facultative chemolithoautotrophic microbe. The novel
technique will facilitate more advanced researches and applications of R.
eutropha for PHA production and CO2 conversion.
PMID- 29951117
TI - Microduplication in the 2p16.1p15 chromosomal region linked to developmental
delay and intellectual disability.
AB - Background: Several patients with the 2p16.1p15 microdeletion syndrome have been
reported. However, microduplication in the 2p16.1p15 chromosomal region has only
been reported in one case, and milder clinical features were present compared to
those attributed to 2p16.1p15 microdeletion syndrome. Some additional cases were
deposited in DECIPHER database. Case presentation: In this report we describe
four further cases of 2p16.1p15 microduplication in four unrelated probands. They
presented with mild gross motor delay, delayed speech and language development,
and mild dysmorphic features. In addition, two probands have macrocephaly and one
a congenital heart anomaly. Newly described cases share several phenotype
characteristics with those detailed in one previously reported microduplication
case. Conclusion: The common features among patients are developmental delay,
speech delay, mild to moderate intellectual disability and unspecific dysmorphic
features. Two patients have bilateral clinodactyly of the 5th finger and two have
bilateral 2nd-3rd toes syndactyly. Interestingly, as opposed to the deletion
phenotype with some cases of microcephaly, 2 patients are reported with
macrocephaly. The reported cases suggest that microduplication in 2p16.1p15
chromosomal region might be causally linked to developmental delay, speech delay,
and mild intellectual disability.
PMID- 29951119
TI - Treatment of paediatric trigger finger: a systematic review and treatment
algorithm.
AB - Purpose: Paediatric trigger finger (PTF) is a rare condition as seen by the lack
of studies published about paediatric populations. Due to this general lack of
information, the steps to employ to correct this disorder, whether surgically or
non-surgically, have not yet reached consensus status. The objective of this
study is to review the published literature regarding treatment options for PTF
in order to develop a proposed step-wise treatment algorithm for children
presenting with trigger finger. Methods: A systematic review of the literature
was conducted on PubMed to locate English language studies reporting on treatment
interventions of PTF. Data was collected on number of patients/fingers seen in
the study, the category of the fingers involved, the number of patients/fingers
undergoing each intervention and reported outcomes. Results: Seven articles
reporting on 118 trigger fingers were identified. In all, 64 fingers were treated
non-surgically, with 57.8% (37/64) resolving. In all, 54 fingers were initially
surgically treated, with 87% (47/54) resolving. In total, 34 fingers did not have
resolution of symptoms following primary treatment, and 27 fingers received
follow-up treatment, with 92.6% (25/27) resolving. Overall, 92.4% (109/118) of
fingers achieved resolution of symptoms after all treatments were completed.
Conclusion: Limitations for this study included few prospective studies and small
sample sizes. This is likely due to the rarity of PTF. This review of the
literature indicated that a step-wise approach, including non-operative and
surgical techniques, should be employed in the management of PTF. Level of
Evidence III: This work meets the requirements of the PRISMA guidelines
(Preferred Reporting Items for Systematic Reviews and Meta-Analyses).
PMID- 29951118
TI - Development of the infant foot as a load bearing structure: study protocol for a
longitudinal evaluation (the Small Steps study).
AB - Background: An improved understanding of the structural and functional
development of the paediatric foot is fundamental to a strong theoretical
framework for health professionals and scientists. An infant's transition from
sitting, through crawling and cruising, to walking is when the structures and
function of the foot must adapt to bearing load. The adaptation of skin and other
hard and soft tissue, and foot and gait biomechanics, during this time is poorly
understood. This is because data characterising the foot tissue and loading pre
walking onset does not exist. Of the existing kinematic and plantar pressure
data, few studies have collected data which reflects the real-life activities of
infants with modern equipment. Methods: This is a longitudinal study and part of
the Great Foundations Initiative, a collaborative project between the University
of Brighton and the University of Salford, which is seeking to improve foot
health in children. Two cohorts of 50 infants will be recruited at the two sites
(University of Brighton, Eastbourne, UK and University of Salford, Salford, UK).
Infants will be recruited when they first reach for their feet and attend four
laboratory visits at milestones related to foot loading, with experienced
independent walking being the final milestone. Data collection will include
tissue characteristics (skin thickness, texture, elasticity, pH and tendon
thickness and cross-sectional area), plantar pressures and kinematics captured
during real world locomotion tasks. Discussion: This study will provide a
database characterising the development of the infant foot as it becomes a weight
bearing structure. The data will allow effective comparison and quantification of
changes in structure and function due to maturation and loading by measuring pre
and post established walking. Additional variables which impact on the
development of the foot (gender, ethnicity and body weight) will also be factored
into our analysis. This will help us to advance understanding of the determinants
of foot development in early childhood.
PMID- 29951120
TI - Foot and ankle deformities in children with Down syndrome.
AB - Purpose: Foot and ankle deformities are common orthopaedic disorders in children
with Down syndrome. However, radiographic measurements of the foot and ankle have
not been previously reported. The aim of this study is to describe the foot and
ankle deformity in children with Down syndrome. Methods: Children who had foot
and ankle radiographs in the standing weight-bearing position were selected.
Three groups of patients were identified. The relationship of radiographic
measurements with age, body mass index and pain is discussed. In all, 41 children
(79 feet) had foot radiographs and 60 children (117 ankles) had ankle
radiographs, with 15 children overlapping between Groups I and II. Results: In
Group I, hallux valgus deformity was seen before ten years of age and hallux
valgus angle increased afterwards. Metatarsus adductus angle showed a significant
increase (p = 0.006) with obesity and was higher in patients who had foot pain (p
= 0.05). In Group II, none of the ankle measurements showed a significant
difference with age or body mass index percentiles. Tibiotalar angle (TTA) and
medial distal tibial angle (MDTA) were higher in patients who had ankle pain. In
Group III, correlation analysis was performed between the different measurements
with the strongest correlations found between TTA and MDTA. Conclusion: In
children with Down syndrome, radiographic evaluation of the foot and ankle
reveals higher prevalence of deformities than clinical examination. However, foot
and ankle radiographs are needed only for symptomatic children with pain and gait
changes. Level of Evidence: Level IV - Prognostic Study.
PMID- 29951121
TI - Femoral and Dega osteotomies in the treatment of habitual hip dislocation in Down
syndrome patients - is it efficient or not?
AB - Purpose: The purpose of this case series study is to report on the intermediate
term outcomes following a femoral varus derotational osteotomy (FVDO) performed
in conjunction with a Dega osteotomy (DO) in management of hip -instability in
Down syndrome (DS) patients. Methods: Ten hips in seven children with DS
suffering from hip dislocation were included. All patients included in this study
had hip dislocation in the habitual phase and painless mobile hip to full
abduction. All patients were firstly subjected to FVDO. An additional DO was
added if intraoperative assessment demonstrated posterior instability. The mean
age at time of surgery was 5.6 years (3 to 7). There were three male and four
female patients. All patients were followed up after two years with a mean follow
up of 3.27 years (2 to 5). All operations were performed by the first author.
Results: There was improvement of neck shaft angles (130 degrees to 175 degrees
, median = 160 degrees preoperatively, to 120 degrees to 140 degrees , median
=130 degrees postoperatively). The Shenton line was restored in all our cases.
There was also improved percentage of the femoral head uncovered by the lateral
wall of the acetabulum (25 degrees to 100 degrees with median = 45 degrees
preoperatively, to 0 degrees to 15 degrees with median = 5 degrees
postoperatively) and improved posterior acetabular coverage, which was assessed
by CT. Conclusion: FVDO combined with DO without -capsulorrhaphy is efficient in
the management of hip instability in DS, as it corrects hip biomechanics and
increases posterior acetabular coverage. Level of Evidence: IV - retrospective
case series.
PMID- 29951122
TI - Increased time between diagnosis and surgery in slipped capital femoral epiphysis
results in increased radiographic deformity.
AB - Purpose: Previous work has examined the impact of delay of diagnosis in slipped
capital femoral epiphysis (SCFE) but not the impact of delay in treatment after
radiographic diagnosis. Due to requirements for long distance transportation from
less developed regions for many of our patients, our hospital was able to study
variation in time between diagnosis and surgery for SCFE, as related to slip
severity. Methods: This is a retrospective review of patients treated for SCFE
between 2005 and 2014 at a tertiary care paediatric hospital. Demographics, time
between diagnosis and surgery, radiographic deformity (Southwick angle),
postoperative complications and need for further surgery were variables of
interest. Statistical analysis included Pearson and Spearman rank correlations
and chi-squared tests. Results: The study sample included 147 hips (119
patients). Mean time between radiographic diagnosis and surgery was 20.9 days (sd
46, 0 to 321). The mean Southwick angle (SA) at the time of surgery was 31.9 (sd
19.6, 1 degrees to 83). There was a significant relationship between increased
delay and increased SA (0.34, p < 0.001). Increased SA was correlated with need
for future significant surgery (0.27, p < 0.01).Patients from less-developed
regions, with barriers to timely care, had moderate and severe deformity (SA) (p
< 0.01), and required significant further surgery more often than SCFE patients
from the local population (p < 0.01). Conclusion: The unique referral environment
of our hospital provided an opportunity to examine traditional recommendations
for treating SCFE promptly after radiographic diagnosis. Delay in treatment is
correlated with increased radiographic deformity. Level of Evidence: III.
PMID- 29951123
TI - Diagnostic and treatment preferences for developmental dysplasia of the hip: a
survey of EPOS and POSNA members.
AB - Purpose: The aim of this study was to elucidate developmental dysplasia of the
hip (DDH) diagnosis and treatment preferences among members of the Pediatric
Orthopaedic Society of North America (POSNA) and European Paediatric Orthopaedic
Society (EPOS). Methods: A 54-question survey on DDH diagnosis and treatment
preferences was distributed to POSNA and EPOS members. Descriptive statistics
were performed. Results: A total of 459 responses were analyzed. Ultrasound was
the preferred modality for diagnosing DDH in infants less than six months old;
few surgeons preferred radiographs. In all, 57% of POSNA members had radiology
technicians perform ultrasounds, only 7% of EPOS members did. The percent
coverage defining a dislocated hip varied greatly, the most frequent response
being < 20% for POSNA and < 40% for EPOS members. Pavlik harnesses were the most
popular harness/brace, used by 90% of POSNA and 71% of EPOS members. POSNA
members were more likely than EPOS members to use a rigid abduction brace
following initial harness/brace failure. For residual acetabular dysplasia, POSNA
members were twice as likely as EPOS members to institute hip abduction bracing.
Most surgeons would not perform closed reduction at less than three months of age
or open reduction at less than six months of age. Most EPOS -members used
traction prior to reduction; few POSNA members did. Few POSNA and EPOS members
believed that reduction should be delayed until the ossific nucleus was visible.
Conclusion: There is great variation in the preferred methods for diagnosing and
treating DDH. This survey is the largest transcontinental survey to compile
diagnostic and treatment preferences for DDH. With wide variations in practice,
there is room for quality improvement. Level of Evidence II:
PMID- 29951124
TI - Minor change in the sulcus angle during the first six years of life: a
prospective study of the femoral trochlea development in dysplastic and normal
knees.
AB - Purpose: The aetiology of femoral trochlear dysplasia is unknown. The aim of this
prospective cohort study was to describe trochlear development in a newborn
population during the first six years of life. Methods: In an earlier study, the
femoral trochlea was examined by ultrasound in 174 newborns. A dysplastic
trochlea was defined with a sulcus angle (SA) above 159 degrees . Two groups were
defined, one group of 15 knees with SA > 159 degrees (dysplastic group), and one
group of 101 knees with SA < 159 degrees (non-dysplastic group). In the present
follow-up study, the children were further examined at six, 18 and 72 months.
Results: There was a statistically significant difference in the SA between the
dysplastic and the non-dysplastic group at all follow-ups (p < 0.001). A small
but statistically significant change in the SA between 0 to 72 months was
detected for the dysplastic knees (p = 0.032) and for the controls (p < 0.001).
Conclusion: Only minor changes in the anatomy of the femoral trochlea from
newborn to age six years were found. A dysplastic trochlea at birth remains
shallow and the anatomy does not change from normal to dysplastic during the same
time span. Level of Evidence: II.
PMID- 29951125
TI - A systematic review of long-term patient reported outcomes for the treatment of
anterior cruciate ligament injuries in the skeletally immature.
AB - Purpose: To systematically review the available literature regarding outcomes for
the treatment of anterior cruciate ligament (ACL) injuries in the skeletally
immature at skeletal maturity or more than five years after surgery. Methods: A
systematic search was performed of seven online databases for literature
reporting patient reported outcomes for the treatment of ACL injuries in the
skeletally immature. A systematic review of this literature was performed
examining the outcomes and their association with skeletal immaturity and
treatment techniques. Results: A total of 18 articles reported the outcomes of
425 subjects. The mean age at surgery ranged from 10.3 to 15 years. Mean follow
up ranged from 36 to 163 months. Ten studies followed up subjects until skeletal
maturity. Mean outcome scores were similar for extraphyseal (Lysholm 96.2 (95.7
to 97.4), Tegner 6.75, IKDC 95.4 (94 to 100)) and transphyseal surgery (Lysholm
94.3 (84.6-100), Tegner 7.6 (6 to 8.7), International Knee Documentation
Committee (IKDC) 93.6 (84 to 99)). However, the lower range boundary for Lysholm
and IKDC was worse for the transphyseal group. The results for non-surgical
treatments were worse (Lysholm 63.2, Tegner 4.8, IKDC 87). No significant
differences were found in the incidence of limb-length discrepancy (p = 0.32),
coronal plane growth disturbance (p = 0.48), graft rupture (p = 0.88) and
persistent symptomatic instability (p = 0.11) with transphyseal and extraphyseal
surgical techniques. Conclusion: Both transphyseal and extraphyseal
reconstructive techniques produced good patient reported outcomes, with no
significant differences in the incidence of limb-length discrepancy, coronal
plane growth disturbance, graft rupture and persistent symptomatic instability.
They compare favourably with the repair techniques reviewed and the natural
history of the condition. Further high-quality studies comparing the transphyseal
and extraphyseal techniques are required. Level of Evidence: Level IV.
PMID- 29951126
TI - Assessment of the ankle joint in clubfeet and normal feet to the age of four
years by ultrasonography.
AB - Purpose: To establish reproducible posterior ultrasonographic projections for
evaluation of the movement in the talocrural joint in clubfeet and normal feet
from the perinatal period up to the age of four years. Methods: The feet in 105
healthy children and 46 patients (71 clubfeet and 21 normal feet) were examined.
In all, 14 feet in seven patients were examined twice by two examiners
independently to evaluate the repeatability of the ultrasonography scans. A
posterior sagittal projection was used. The distance from the posterior aspect of
the tibial physis to the posterior border of the talocalcaneal joint (Tib. phys -
TCJ) was measured with the foot in neutral position and dorsiflexion. In plantar
flexion the shortest distance between the tibial physis and the calcaneus was
measured. The distance from the skin to the tibial epiphyses and the talus was
measured in neutral position. The intraclass correlation coefficient (ICC) was
calculated to evaluate the repeatability of the measurements. Results: The
interexaminer reliability was 0.71 to 0.89 ICC. The intra- and interobserver
reliability measured as ICC was 0.68 to 0.99 for all measurements. The
correlation between Tib. phys. - TCJ and clinical dorsiflexion varied much
between the age groups. Conclusion: Ultrasonography of the posterior aspect of
the ankle joint can be done with high interexaminer reliability. The
repeatability of image evaluation was high. Correlation to clinical measurements
varied, therefore dynamic ultrasound in real time is clinically more useful than
single measurements on frozen ultrasound images. Level of Evidence III:
PMID- 29951127
TI - Percutaneous heel cord release for clubfoot: a retrospective, multicentre cost
analysis.
AB - Purpose: The Ponseti method of treatment is the standard of care for idiopathic
clubfoot. Following serial casting, percutaneous tendo-Achilles tenotomy (TAT) is
performed to correct residual equinus. This procedure can be performed in either
the outpatient clinic or the operating room. The purpose of this study was to
evaluate the expense of this procedure by examining hospital charges in both
settings. Methods: We retrospectively reviewed charts of 382 idiopathic clubfoot
patients with a mean age of 2.4 months (0.6 to 26.6) treated with the Ponseti
method at three institutions. Patients were divided into three groups depending
on the setting for the TAT procedure: 140 patients in the outpatient clinic (CL),
219 in the operating room with discharge following the procedure (OR) and 23 in
the operating room with admission to hospital for observation (OR+). Medical
records were reviewed to analyze age, deformity, perioperative complications and
specific time spent in each setting. Hospital charges for all three groups were
standardized to one institution's charge structure. Results: Charges among the
three groups undergoing TAT (CL, OR, OR+) were found to be significantly
different ($3840.60 versus $7962.30 versus $9110.00, respectively; p <= 0.001),
and remained significant when separating unilateral and bilateral deformities (p
< 0.001). There were nine total perioperative complications (six returns to the
ER and three unexpected admissions to the hospital): five (2.3%) in the OR group,
four (17.4%) in the OR+ group and none in the CL group. The OR+ group
statistically had a higher rate of complications compared with the other two
groups (p = 0.006). The total event time of the CL group was significantly
shorter compared with the OR and OR+ groups (129.1, 171.7 and 1571.6 minutes
respectively; p < 0.001). Conclusion: Hospital charges and total event time were
significantly less when percutaneous TAT was performed in the outpatient clinic
compared with the operating room. In addition, performing the procedure in clinic
was associated with the lowest rate of complications. Level of Evidence:
Therapeutic, Level III.
PMID- 29951128
TI - Prophylactic antibiotics in soft-tissue procedures in children with cerebral
palsy.
AB - Purpose: Data on the benefits of perioperative prophylactic antibiotics in the
paediatric population are lacking. In this study, we aimed to assess the rate of
infection after isolated soft-tissue procedures in patients with cerebral palsy
with and without preoperative prophylactic antibiotics between 2009 and 2015.
Methods: We reviewed the records of all children with cerebral palsy who
underwent isolated soft-tissue procedures (on the upper and lower limb) at our
hospital between 2009 and 2015. Children with at least 30-day postoperative
follow-up were included. Children who had groin incisions were excluded. Results:
Two groups were identified: the antibiotic group (77 children with 203 incisions
and 343 procedures) had one surgical site infection; the no-antibiotic group (48
children with 102 incisions and 177 procedures) had no surgical site infections.
Conclusion: These results suggest that the use of preoperative antibiotics does
not change the rate of postoperative surgical site infections. Level of Evidence:
Level III therapeutic study.
PMID- 29951129
TI - Are inflatable play structures really safe for our children?
AB - Purpose: The frequency of injuries sustained while playing on inflatable toys
such as bouncy castles have rapidly increased. These supposedly safe structures
are likely unsafe. The objective of this review was to investigate the risk that
these attractions represent and the necessary measures to minimize risk of
accidents. Methods: We conducted a prospective study of 114 patients over a
period of one year (2015 to 2016). Demographic data collected included: age,
gender, anatomical location and side of involvement as well as supervision of the
child whilst on the bouncy castle. The extracted data include mechanism of injury
and risk factors, i.e. lack of supervision of the child, amounts of users jumping
at the same time. Results: The injuries were slightly more frequent in male than
female children; 2:1 up to six years of age. From the age of ten to 14 years the
ration evened to 1:1, the higher incidence in female children was between the
ages of six to eight years.The most common injuries were to the humerus, followed
by the distal radius. Only 28% of the parents said they were supervising while
the child was jumping. Conclusion: Injuries associated with inflatable bouncers
have increased over time. The main risk factors: were lack of effective adult
supervision and the shared use by an excessive number of participants of
different ages and weights.These considerations lead to the conclusion that there
is a necessity to enhance child health surveillance and to consider limiting
bouncer usage to children over the age of six years, to prevent and control
injuries and to minimize their consequences. Level of Evidence: II - prospective
study.
PMID- 29951130
TI - Postponing surgery of paediatric supracondylar humerus fractures to office hours
increases consultant attendance in operations and saves operative room time.
AB - Purpose: To assess if postponing surgery of paediatric supracondylar humerus
fractures (SCHF) without compromised blood circulation to office hours can
improve the quality of reduction and pin fixation and decrease complications.
Methods: In 2004, night-time (0am to 7am) surgery was allowed only for children
with compromised blood circulation. Number of open reductions, surgeons
experience, operation time, quality of reduction (Baumann angle, anterior humeral
line crossing point with capitellum) and pin fixation as well as the number of
complications were compared in 100 children before (A) and 100 after (B) the new
protocol. Surgery was commenced during office hours (8am to 3pm) in 27% (A)
versus 55% (B) and delay to surgery from admission exceeded six hours in 25% (A)
versus 52% (B) of the children. Results: Open reduction was performed in eight
(A) versus 11 (B) children. In group A, 40% were operated on by a registrar alone
compared with 14% in group B. Mean operation room time decreased by 11 minutes in
group B. Radiographic alignment was satisfactory at fracture union in 68% (A)
versus 68% (B) and radiologically stable pin fixation in 42% (A) versus 55% (B)
of children (p = 0.08). The was no statistical difference in admission time, re
reductions, infections, permanent iatrogenic nerve injuries or corrective
osteotomies between the patient groups. Conclusions: No statistical difference in
quality of reduction or pin fixation or in number of complications was observed.
Postponing operative treatment of SCHF without vascular compromise increased
consultant attendance in operations and decreased operative room time. Level of
Evidence: III - retrospective comparative study.
PMID- 29951131
TI - Type 2 diabetes and cardiometabolic risk may be associated with increase in DNA
methylation of FKBP5.
AB - Background: Subclinical hypercortisolism and hypothalamic-pituitary-adrenal (HPA)
axis dysfunction are associated with type 2 diabetes (T2DM), cardiovascular
disease, and metabolic dysfunction. Intronic methylation of FKBP5 has been
implicated as a potential indicator of chronic cortisol exposure. Our overall
objective in this study was to determine the association of chronic cortisol
exposure, measured via percent methylation of FKBP5 at intron 2, with percent
glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL
cholesterol), waist circumference (WC), and body mass index (BMI), in a clinic
based sample of 43 individuals with T2DM. Results: Greater percent methylation of
the FKBP5 intron 2 at one CpG-dinucleotide region was significantly associated
with higher HbA1c (beta = 0.535, p = 0.003) and LDL cholesterol (beta = 0.344, p
= 0.037) and a second CpG-dinucleotide region was significantly associated with
higher BMI and WC (beta = 0.516, p = 0.001; beta = 0.403, p = 0.006,
respectively). Conclusions: FKBP5 methylation may be a marker of higher metabolic
risk in T2DM, possibly secondary to higher exposure to cortisol. Further work
should aim to assess the longitudinal association of FKBP5 with cardiovascular
disease and glycemic outcomes in T2DM as a first step in understanding potential
preventive and treatment-related interventions targeting the HPA axis.
PMID- 29951132
TI - Acute leukemia cells resistant to PI3K/mTOR inhibition display upregulation of
P2RY14 expression.
AB - The PI3K/mTOR pathway is the second most frequently deregulated pathway in a
majority of cancers such as breast cancer, lung cancer, and melanomas as well as
leukemia. Mutations in the genes coding for receptor tyrosine kinases (RTKs) and
G-protein-coupled receptors (GPCRs) are quite common in all forms of acute
leukemia. This can be a major cause of deregulation of the PI3K-mTOR pathway. To
understand how cells display resistance to the dual PI3K/mTOR inhibitor, we used
a panel of 25 acute leukemia cell lines. We observed that while a number of cell
lines displayed sensitivity to the dual PI3K/mTOR pathway inhibitor PKI-587, many
cells displayed substantial resistance. Cells sensitive to PKI-587 also showed
aberrant activation of PI3K/mTOR pathway components such as AKT and S6K and also
displayed sensitivity to a panel of various other PI3K/mTOR inhibitors. Using RNA
sequencing data, we observed that expression of a G protein-coupled receptor,
P2RY14, was upregulated nine-fold in cells showing resistance to the PI3K/mTOR
inhibitor. P2RY14 has not been much studied in hematologic malignancies. However,
this receptor seems to have a role in the localization of hematopoietic stem
cells (HSCs) and in promoting regenerative capabilities following injury. We
observed that acute lymphoblastic leukemia (ALL) and FLT3-ITD-positive acute
myeloid leukemia (AML) patients with higher expression of P2RY14 mRNA displayed
relatively poor survival compared to patients carrying lower expression of P2RY14
suggesting a role of P2RY14 in patient survival. To understand the role of this
receptor in cell signaling, we used phospho-protein arrays and observed
activation of distinct signaling cascades. Furthermore, array data were verified
using murine pro-B cell line Ba/F3 stably transfected with P2RY14. We observed
that activation of P2RY14 by its ligand, UDP-glucose, resulted in selective
induction of ERK1/2 phosphorylation. Taken together, our data suggest that acute
leukemia cells resistant to PI3K/mTOR inhibition display upregulation of a GPCR,
P2RY14, which has a role in patient survival and also couples to the activation
of ERK signaling.
PMID- 29951133
TI - Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines.
AB - Hericium erinaceus, an ideal culinary-medicinal mushroom, has become a well
established candidate in promoting positive brain and nerve health-related
activities by inducing the nerve growth factor from its bioactive ingredient.
Among its active compounds, only erinacine A has confirmed pharmacological
actions in the central nervous system in rats. Hence, this review has summarized
the available information on the neurohealth properties of H. erinaceus mycelia
enriched with erinacines, which may contribute to further research on the
therapeutic roles of these mycelia. The safety of this mushroom has also been
discussed. Although it has been difficult to extrapolate the in vivo studies to
clinical situations, preclinical studies have shown that there can be
improvements in ischemic stroke, Parkinson's disease, Alzheimer's disease, and
depression if H. erinaceus mycelia enriched with erinacines are included in daily
meals.
PMID- 29951134
TI - Maintenance of memory-type pathogenic Th2 cells in the pathophysiology of chronic
airway inflammation.
AB - Background: Immunological memory is critical for long-standing protection against
microorganisms; however, certain antigen-specific memory CD4+ T helper (Th) cells
drive immune-related pathology, including chronic allergic inflammation such as
asthma. The IL-5-producing memory-type Tpath2 subset is important for the
pathogenesis of chronic allergic inflammation. This memory-type pathogenic Th2
cell population (Tpath2) can be detected in various allergic inflammatory
lesions. However, how these pathogenic populations are maintained at the local
inflammatory site has remained unclear. Methods: We performed a series of
experiments using mice model for chronic airway inflammation. We also
investigated the human samples from patients with eosinophilic chronic
rhinosinusitis. Results: We recently reported that inducible bronchus-associated
lymphoid tissue (iBALT) was shaped during chronic inflammation in the lung. We
also found that memory-type Tpath2 cells are maintained within iBALT. The
maintenance of the Tpath2 cells within iBALT is supported by specific cell
subpopulations within the lung. Furthermore, ectopic lymphoid structures
consisting of memory CD4+ T cells were found in nasal polyps of eosinophilic
chronic rhinosinusitis patients, indicating that the persistence of inflammation
is controlled by these structures. Conclusion: Thus, the cell components that
organize iBALT formation may be therapeutic targets for chronic allergic airway
inflammation.
PMID- 29951135
TI - Brugada syndrome and sinus node dysfunction.
AB - Brugada syndrome (BrS) is a well-known catastrophic disease first reported in
1992 by the Brugada brothers. Ventricular fibrillation (VF) is an essential
arrhythmia in BrS. An association between BrS and atrial tachyarrhythmias is not
uncommon. However, sinus node dysfunction (SND) associated with BrS has not been
well discussed. In this review, we focus on the association between BrS and SND.
Based on previous reports describing clinical, epidemiological, and genetic
evidence, SND is not a rare concomitant disorder in BrS. BrS may be a multiple
conduction or arrhythmogenic disorder including not only the His-Purkinje system
and right ventricle, but also the sinus node and atrium, derived from ion channel
mutations.
PMID- 29951136
TI - Signal-averaged electrocardiography: Past, present, and future.
AB - Signal-averaged electrocardiography records delayed depolarization of myocardial
areas with slow conduction that can form the substrate for monomorphic
ventricular tachycardia. This technique has been examined mostly in patients with
coronary artery disease, but its use has been declined over the years. However,
several lines of evidence, derived from hitherto clinical data in patients with
healed myocardial infarction, indicate that signal-averaged electrocardiography
remains a valuable tool in risk stratification, especially when incorporated into
algorithms encompassing invasive and noninvasive indices. Such an approach can
aid the more precise identification of candidates for device therapy, in the
context of primary prevention of sudden cardiac death. This article reappraises
the value of signal-averaged electrocardiography as a predictor of arrhythmic
outcome in patients with ischemic heart disease and discusses potential future
indications.
PMID- 29951137
TI - Evaluation of the atrial substrate based on low-voltage areas and dominant
frequencies after pulmonary vein isolation in nonparoxysmal atrial fibrillation.
AB - Background: This study aimed to evaluate the atrial substrate in the left atrium
(LA) by low-voltage areas (LVAs) and high-dominant frequencies (DFs) after
circumferential pulmonary vein isolation (PVI) in nonparoxysmal atrial
fibrillation (AF). Methods: In 70 patients with nonparoxysmal AF patients (41
persistent AF), LA voltage maps were created during sinus rhythm by external
cardioversion after PVI and DF mapping. The patients were divided into AF-free
and AF-recurrent groups. Results: The AF freedom rate without antiarrhythmic
drugs was 69.0% after PVI after 1 procedure during a 12-month follow-up. There
was a significant difference in the LVA (<0.5 mV)/LA surface area after PVI
between the AF-free and AF-recurrent groups (15% vs 23%, P = .033). AF freedom
was significantly greater in those with LVAs of <=24% than in those with LVAs of
>24% during 12 months of follow-up (78.6% vs 53.8%, Log-rank test P = .020).
Fifty-six (72%) of the 78 high-DF sites (>=8 Hz) overlapped with LVAs. Thirty-one
(55%) of 56 high-DF sites overlapped with LVAs that existed at LVA border zones.
There were no significant differences in number of high-DF sites that overlapped
with LVAs in the LA between the two groups. However, in persistent AF patients,
the max-DF value in the LA exhibited a significant difference between the two
groups (P = .008). Conclusions: LVAs were associated with AF recurrences after
PVI in nonparoxysmal AF patients and overlapped with many high-DF sites. PVI
alone may be enough to treat patients with mild-to-moderate extent (<=24%) of
LVAs.
PMID- 29951138
TI - Comparison of the efficacy between impedance-guided and contact force-guided
atrial fibrillation ablation using an automated annotation system.
AB - Background: This study compared the efficacy of catheter ablation of atrial
fibrillation (AF) between impedance (IMP)-guided and contact force (CF)-guided
annotation using the automated annotation system (VisiTagTM). Methods: Fifty
patients undergoing pulmonary vein isolation (PVI) for AF were randomized to the
IMP-guided or CF-guided groups. The annotation criteria for VisiTagTM were a 10
second minimum ablation time and 2 mm maximum catheter movement range. A minimum
CF of 10 g was added to the criteria in the CF-guided group. In the IMP-guided
group, a minimum IMP drop of over 5 Omega was added to the criteria. Results: The
rates of successful PVI after an initial ablation line were higher in the CF
guided group (80% vs 48%, P = .018). Although average CF was similar between two
groups, the average force-time integral (FTI) was significantly higher in the CF
guided group (298.3 +/- 65. 2 g.s vs 255.1 +/- 38.3 g.s, P = .007). The atrial
arrhythmia-free survival at 1 year demonstrated no difference between the two
groups (84.0% in the IMP-guided group vs 80.0% in the CF-guided group, P = .737).
If the use of any antiarrhythmic drug beyond the blanking period was considered
as a failure, the clinical success rate at 1 year was 52.0% for the CF-guided
group vs 56.0% for the IMP-guided group (P = .813). Conclusions: Atrial
fibrillation ablation using an automated annotation system guided by CF improved
the success rate of PVI after the initial circumferential ablation. An IMP-guided
annotation combined with catheter stability criteria showed similar clinical
outcomes as compared to the CF-guided annotation.
PMID- 29951139
TI - Impact of impedance decrease during radiofrequency current application for atrial
fibrillation ablation on myocardial lesion and gap formation.
AB - Background: The clinical impact of a decrease in impedance during radiofrequency
catheter ablation (RFCA) has not been fully clarified. The aim of the study was
to analyze the impact of impedance decrease and to determine its optimal cutoff
value during RFCA. Methods: We evaluated 34 consecutive patients (total 3264
lesions, mean age 66 +/- 8.7 years, 10 females) who underwent their first
ablation for atrial fibrillation (AF). The impedance decrease, average contact
force (CF), application time, force-time integral (FTI), product of impedance
decrease and application time (PIT), and the product of impedance decrease and
FTI (PIFT) were measured for all lesions. Levels of cardiac troponin I (TrpI)
were measured for assessment of myocardial injury. The incidence of
intraprocedural pulmonary vein-left atrium reconnection or dormant conduction
(reconnection) was determined. The relationships between the ablation parameters
and the increase in TrpI (DeltaTrpI) were evaluated. The predictive value of the
parameters for reconnection was assessed using receiver operating characteristic
(ROC) curve analysis. Results: Reconnection was detected in 18 patients. Average
FTI and PIT were significantly correlated with DeltaTrpI (FTI: r2 = .19, P =
.0090, PIT: r2 = .21, P = .0058). PIFT was correlated with DeltaTrpI and was the
best of the three indexes (PIFT: r2 = .29, P = .0010). In ROC curve analysis, the
area under the curve for predicting reconnection was 0.71 and the optimal cutoff
value was 5200 for PIFT (sensitivity 78%, specificity 63%). Conclusion: The
combination of CF and a decrease in impedance could be important in the
evaluation of myocardial lesions and reconnection during RFCA.
PMID- 29951140
TI - Nonsustained ventricular tachycardia does not affect the prognosis of
neuromuscular diseases: A preliminary and retrospective study.
AB - Background: Nonsustained ventricular tachycardia (NSVT) is sometimes observed in
patients with neuromuscular diseases (NMDs). The aim of this study was to assess
the role of NSVT in the survival prognosis of NMD patients. Methods: We
retrospectively analyzed the patients with NMDs who had undergone Holter ECG
recordings at a single center between February and August 2012. Sixty-eight
patients were enrolled in this study. The 5 year follow-up was assessed according
to the cumulative event-free rate. Results: Twenty-one patients died during the
follow-up, seven of whom died by cardiac death. The Kaplan-Meier survival curve
that compared the patients with NSVT and those without NSVT indicated the NSVT
was not related to the rate of all causes of death or cardiac death in those
patients with NMDs. The survival curve was not significantly changed after the
adjustment by age and ejection fraction. Conclusion: No significant correlations
between NSVT and the prognosis in patients with NMDs were found.
PMID- 29951141
TI - Investigation on the optimal implantation site and setting of Reveal LINQ(r)
avoiding interference with performance of transthoracic echocardiography.
AB - Background: The optimal implantation site of a new implantable cardiac monitor
(ICM) named Reveal LINQ(r) may be limited based on a sufficient amplitude of R
wave potential (AEP) acquisition because it is the same anatomic area used for
transthoracic echocardiography (TTE). Methods: Among 18 healthy volunteers, we
assessed AEPs in 3 combinations through parasternal placement of 2 electrodes,
(i) in the 4th intercostal space (ICS; site A/setting a; A/a), (ii) the same
setting in the 5th ICS (site B/setting a; B/a), and (iii) in a sagittal plane
relative to the left sternal border at the 4th ICS (site A/setting b; A/b), and
further measured AFPs in several body positions in all site-setting combinations:
supine, left and right lateral decubitus, sitting, and standing. The degree of
interference with TTE performance was assessed by placement of an imitation ICM
in setting a at both sites A and B. Results: Only the AEPs in A/a and B/a met the
criteria (AEP >= 0.3 mV) in all positions. The AEPs in the supine position with
all combinations were higher than those achieved in other positions (P < .001).
The imitation interfered with TTE performance at site A among 78% of subjects,
but only 17% at site B (P = .0006). The end-diastolic dimension of the left
ventricle at site A was decreased after the imitation placement (P = .028). At
site B, all female subjects complained of discomfort because their brassieres
overlaid the imitation. Conclusion: The B/a combination is optimal; however, the
personal discomfort related to brassieres should be considered.
PMID- 29951142
TI - Effect of heart rate and pacing mode on QRS fragmentation.
AB - Background: The study was designed to investigate the effect of heart rate and
pacing mode on QRS fragmentation (f-QRS). Moreover, the usefulness of f-QRS in
distinguishing patients with impaired left ventricular ejection function (EF) and
ventricular tachycardia (VT) from patients with normal EF was assessed. Methods:
Three hundred and six recipients, with dual-chamber device, with intrinsic narrow
or wide QRS complex and preserved atrioventricular conduction were grouped into
normal-EF or impaired-EF VT. We analyzed intrinsic narrow f-QRS and wide f-QRS as
well as ventricular-paced f-QRS following different heart rates (baseline, 100
bpm) and pacing modes. Results: In the baseline state, overall, patients with
impaired-EF VT (35 +/- 9%), compared to those with normal-EF, had more f-QRS (56%
vs 27%, P < .001) and ventricular-paced f-QRS (62% vs 16%, P < .0001).
Ventricular pacing conferred both at baseline and at higher heart rate more
ventricular-paced f-QRS in patients with impaired-EF VT than in normal-EF (P <
.001). Detection of ventricular-paced f-QRS markedly improved overall specificity
(84%) and positive predictive value (91%) in identifying patients with impaired
EF VT. Conclusions: Increased heart rate or/and ventricular pacing uncover QRS
fragmentations. Detection of ventricular-paced f-QRS adds value toward
noninvasive identification of patients with impaired-EF VT.
PMID- 29951143
TI - Electrical remodelling and response following cardiac resynchronization therapy:
A novel analysis of intracardiac electrogram using a quadripolar lead.
AB - Background: Cardiac resynchronization therapy (CRT) improves morbidity and
mortality in patients with heart failure. Although structural remodelling
correlates with improved long-term outcomes, the role of electrical remodelling
is poorly understood. This study aimed to evaluate electrical remodelling
following CRT using a quadripolar left ventricular (LV) lead and to correlate
this with structural remodelling. Methods: Consecutive patients undergoing
initial CRT implantation using a quadripolar LV lead were enrolled. Patients were
followed up for 12 months. Twelve lead ECG, transthoracic echocardiogram, and
evaluation of intracardiac electrograms (EGM) were performed. Measures included
right and left ventricular lead intrinsic delay, RV-pacing to LV-sensing (RVp
LVs) delay, and LV-pacing to RV-sensing (LVp-RVs) delay. The electrical changes
were then correlated with echocardiographic response to CRT, defined by >=15%
relative reduction in LVESV and >= 5% absolute improvement in EF on TTE.
Activation sequence was determined using the quadripolar lead. Results: Forty
patients were enrolled. Mean intrinsic RV-LV EGM values decreased from 121.9 +/-
14.7 ms to 109.1 +/- 15.0 ms (P < .01), mean RVp-LVs EGM values from 146.7 +/-
16.7 ms to 135.1 +/- 13.1 ms, (P < .01), and mean LVp-RVs EGM values from 155.7
+/- 18.1 ms to 144.2 +/- 17.1 ms (P < .01). The improvement in intrinsic RV-LV
EGM was 14.9 +/- 8.5 ms in responders vs 8.9 +/- 7.9 ms in nonresponders to CRT
(P < .05). Changes in activation sequence did not correlate with CRT response.
Conclusions: This novel study used EGMs from a quadripolar LV lead to demonstrate
electrical remodelling occurs following CRT. A nonsignificant trend suggests that
electrical remodelling in CRT is greater in responders compared to nonresponders,
although further study is needed.
PMID- 29951144
TI - IL-10(-592A/C) gene variant a predictor of postoperative atrial fibrillation in
the north Indian population.
AB - Background: There is an accumulating body of evidence indicating a strong
association between inflammation and the pathogenesis of atrial fibrillation (AF)
in different ethnicities across the globe. AF increases the risk of stroke and
heart failure. Despite various researches on IL-10 response, there is limited
clinical evidence present, which demonstrate a role of these immunity regulators
in AF. Therefore, this study was designed to decipher the role of IL-10(-592A/C)
polymorphism in the development of postoperative AF (post-OP AF). Method: The
study was designed for north Indian patients. The study included 90 patients with
AF and 126 controls in sinus rhythm undergoing surgery at Department of
Cardiovascular and thoracic surgery, SGPGIMS, Lucknow, India. DNA samples were
genotyped for common single nucleotide polymorphism (SNP) in gene IL-10(-592A/C).
The PCR-based RFLP technique was used to assess the genotype frequencies. The
multivariable logistic regression analysis was performed to study the association
of other risk factors with AF. Results: The distribution of IL-10(-592A/C)
genotypes (CC, AC, and AA) was found to be 48.41%, 47.61%, and 3.98% in controls
and 41.11%, 45.55%, and 13.34% in cases, respectively (P = .0385). The frequency
of allele A in cases was significantly higher than the control group (36.11% vs
27.77%, P = .0654). Compared with CC, AA genotype had increased risk of AF in
both unadjusted and adjusted analyses. Conclusions: This study suggests that IL
10(-592A/C) polymorphism may have significant association with post-OP AF
development in north Indian patients.
PMID- 29951145
TI - Detection of a new KCNQ1 frameshift mutation associated with Jervell and Lange
Nielsen syndrome in 2 Iranian families.
AB - Jervell-Lange Nielsen syndrome (JLNS) with autosomal recessive inheritance is a
congenital cardiovascular disorder characterized by prolongation of QT interval
on the ECG and deafness. We have performed molecular investigation by haplotype
analysis and DNA Sanger sequencing in 2 unrelated Iranian families with a history
of syncope. Mutational screening of KCNQ1 gene revealed the novel homozygous
frameshift mutation c.733-734delGG (p.G245Rfs*39) in 2 obviously unrelated cases
of JLNS which is probably a founder mutation in Iran. The novel mutation detected
in this study is the first time reported among Iranian population and will be
beneficial in the tribe and region-specific cascade screening of LQTS in Iran.
PMID- 29951146
TI - Three cases of catecholaminergic polymorphic ventricular tachycardia with
prolonged QT intervals including two cases of compound mutations.
AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the
leading causes of sudden arrhythmic death in the young. The QT interval in CPVT
patients is typically within the normal range. However, those with prolonged QT
interval have often been diagnosed with mutation-negative long QT syndrome
(LQTS). We report three CPVT patients with prolonged QT interval. Case 1 and 2
were diagnosed as LQTS at first. Genetic test using next-generation sequencing
(NGS) revealed RyR2 mutations. We should consider genetic test using NGS to
identify the genes responsible for CPVT in mutation-negative LQTS.
PMID- 29951147
TI - Atrial tachycardia related to local abnormal atrial activity.
AB - A 42-year-old woman without a history of catheter ablation or cardiac surgery was
referred to our institution for a paroxysmal atrial tachycardia (AT). Programed
stimulation could not induce any AT. The AT spontaneously initiated during a
continuous isoproterenol infusion. The earliest activation during the AT was
recorded at the cavo-tricuspid isthmus, and local abnormal atrial activity
(LAATA) was recorded during sinus rhythm at that same site. When rapid atrial
activity was recorded at the cavo-tricuspid isthmus where the LAATA was recorded,
an AT was induced. Radiofrequency ablation was performed over the entire area
where the LAATA was recorded during sinus rhythm, rendering the AT non-inducible.
PMID- 29951148
TI - High-resolution 3D mapping of epicardial conduction during Marshall bundle
related atrial tachycardia.
AB - A 73-year-old woman was admitted for atrial tachycardia (AT) ablation. The
activation map and pacing study indicated that the AT propagated around the left
pulmonary vein and that the Marshall bundle (MB) bypassed the scar area of the
left pulmonary vein ridge and mitral isthmus. The Rhythmia Mapping System
revealed double potentials propagated along the assumed position of the MB. The
mapping system includes a confidence mask that can be used to visually identify
low-confidence areas of the map based upon extremely low-voltage signals. Given
the low-voltage area in the endocardial side, the epicardial conduction was
emphasized.
PMID- 29951149
TI - Left atrial low-voltage zone ablation of persistent atrial fibrillation in a
patient with myotonic dystrophy: A case report.
AB - We here report a case of a 32-year-old man with genetically diagnosed myotonic
dystrophy and persistent atrial fibrillation (AF) who underwent a low-voltage
zone (LVZ) ablation. His cardiac function was normal except for a prophylactic
pacemaker implantation for a high risk of complete atrioventricular block. An LVZ
was found in the anteroseptal left atrium during sinus rhythm and was ablated
during induced AF after a pulmonary vein antrum isolation, which terminated the
AF and rendered it noninducible by rapid pacing and/or isoproterenol. During 20
months of follow-up, no atrial tachyarrhythmias were observed with pacemaker
monitoring of antiarrhythmic drugs.
PMID- 29951150
TI - A case of paroxysmal atrial fibrillation in a patient successfully treated by
radiofrequency catheter ablation with a severely right-sided dislocation of the
heart after a total right lung excision.
AB - A 72-year-old woman with symptomatic and drug-refractory paroxysmal atrial
fibrillation (AF) underwent radiofrequency catheter ablation (RFCA). She had a
history of a total right lung excision. Her chest X-ray and computed tomography
(CT) revealed a severely sight-sided dislocation of the heart. Thus, the
procedure was carefully performed under guidance of a CT, intracardiac echogram,
atriography, and 3D mapping system. Finally, the AF was successfully treated by
RFCA without any complications.
PMID- 29951151
TI - Typical atrial flutter mimicking a pacemaker-mediated tachycardia.
AB - A 64-year-old man with a history of congestive heart failure secondary to
nonischemic cardiomyopathy, mitral and aortic valve replacements, and
biventricular cardioverter-defibrillator placement, developed a tachycardia. The
tachycardia exhibited a biventricular paced rhythm with a short R-P interval and
concentric atrial activation sequence within the coronary sinus, suggesting that
the tachycardia might be a pacemaker-mediated tachycardia (PMT). However, the
tachycardia was diagnosed as counterclockwise cavotricuspid isthmus (CTI)
dependent atrial flutter (AFL), and linear ablation of the CTI eliminated the
tachycardia. This case illustrated that typical AFL can mimic a PMT when there is
a severe conduction delay through the CTI.
PMID- 29951152
TI - Spontaneous transformation of a concealed to manifest posteroseptal accessory
pathway requiring epicardial ablation.
AB - Concealed accessory pathways (APs) are considered benign as they can only sustain
orthodromic atrioventricular re-entrant tachycardia (ORT). We describe a unique
case of a concealed posteroseptal AP where longitudinal surveillance following
repeated failed ablation attempts due to abnormal coronary sinus (CS) anatomy
revealed spontaneous development of manifest pre-excitation. The pathway was
ultimately ablated via the percutaneous epicardial approach. The potential for
development of Wolff-Parkinson-White (WPW) syndrome in patients with concealed
APs has implications for ongoing surveillance in these patients.
PMID- 29951153
TI - Electrical storm in an infant with short-coupled variant of torsade de pointes.
AB - A 10-month-old infant experienced cardiac arrest caused by ventricular
fibrillation (VF). His electrocardiogram (ECG) at rest was within the normal
range. Amiodarone was indispensable due to its refractoriness to defibrillation.
After implantable cardioverter defibrillator (ICD) implantation, ICD shock was
delivered. ICD recordings documented VF and ventricular tachycardia (VT)
triggered by premature ventricular contractions with an extremely short coupling
interval (240 ms), which were controlled by verapamil. To the best of our
knowledge, our case is the first infant with ScTdP. As the electrical storm with
ScTdP occurs unpredictably, it can be a cause of sudden infant death syndrome.
PMID- 29951154
TI - Very late perforation by a Riata implantable cardioverter-defibrillator lead-A
case report.
AB - Cardiac perforation by a transvenous lead is an uncommon but serious
complication. We herein present a case of very late perforation of a Riata
implantable cardioverter-defibrillator lead, which occurred 8 years after
implantation. The patient was successfully treated with percutaneous lead
extraction using an excimer laser. Lead perforation should be considered, even
after years from implantation.
PMID- 29951155
TI - Iatrogenic subclavian arteriovenous fistula during permanent pacemaker
implantation: Closed by endovascular coiling.
AB - Iatrogenic arteriovenous fistula is a unique complication during pacemaker
implantation. A 55-year-old man was posted for pacemaker implantation for
recurrent unexplained syncope with trifascicular AV block. After
axillary/subclavian venous puncture and introduction of RV lead, arterial
spurting was immediately noticed as the the sheath was peeled away. After
dissecting the overlying pectoralis muscle, deep sutures and manual compression
achieved hemostasis. However, Subclavian arteriogram revealed an arteriovenous
fistula from a lateral thoracic artery branch to the innominate vein. Hilal coils
were deployed near the fistulous orifice, leading to complete resolution of the
leak. After 3 days, pacemaker was implanted from right side. A multidisciplinary
approach was the key to successful outcome.
PMID- 29951156
TI - Subclinical cardiac perforation caused by a MicraTM leadless pacemaker.
AB - A subclinical cardiac perforation by a device cup of the MicraTM transcatheter
pacing system was suspected in a 78-year-old woman. During the procedure, the
device cup was placed on the septum. The contrast media was injected before
device deployment and remained outside of the myocardium. Later, a cardiac
computed tomography scan visualized a protruded diverticular structure on the
right ventricle. The contrast material remained in a pouch within the
pericardium. To ensure the device is oriented away from the border between the
right ventricular septum and the free wall, right anterior oblique view should be
carefully reviewed before deployment.
PMID- 29951157
TI - Hybrid minimally invasive technique with the bidirectional rotational
Evolution(r) mechanical sheath for transvenous lead extraction: A collaboration
between electrophysiologists and cardiac surgeons.
AB - We report a case of a 63-year-old man referred for lead extraction with the
bidirectional rotational Evolution (r) RL mechanical sheath because of systemic
infection. As it was judged a "high-risk" procedure, we opted for a "hybrid,"
minimally invasive approach consisting in a minithoracotomic access. This
technique is a feasible approach, and it might be a potential safer alternative
in the most challenging transvenous lead extraction procedures.
PMID- 29951158
TI - Defibrillation failure: Considerations.
PMID- 29951159
TI - Corrigendum to "Fully Covered Metallic Stents for the Treatment of Benign Airway
Stenosis".
AB - [This corrects the article DOI: 10.1155/2016/8085216.].
PMID- 29951160
TI - Matching Inhaler Devices with Patients: The Role of the Primary Care Physician.
AB - Poor inhaler technique and nonadherence impair the efficacy of medications for
asthma and chronic obstructive pulmonary disease (COPD). A range of factors,
including age, dexterity, inspiratory capacity, cognitive ability, health
literacy, and ethnicity, can impact a patient's ability and intention to use
their device. Treatment success can also be influenced by patient preferences and
perceptions. Therefore, it is important that healthcare professionals effectively
match inhaler devices to individual patients' needs and abilities and empower
patients by including them in treatment decisions. Physicians must, therefore,
fully understand the characteristics of each device, as well as their patients'
demographic characteristics and comorbidities. Following device selection,
patient training and education, including a physical demonstration of the device,
are key to eliminate any critical errors that may impact on health outcomes.
Inhaler technique should be frequently rechecked. This review will examine the
important role of primary care providers in the selection of appropriate inhaler
devices and provision of training for patients with COPD and asthma to optimize
correct inhaler use and adherence. An overview of the key features of available
devices and of the factors to consider when selecting devices will be provided in
the context of current asthma and COPD guidelines.
PMID- 29951161
TI - Response to: Comment on "Prevalence, Etiology, and Risk Factors of Tinea Pedis
and Tinea Unguium in Tunisia".
PMID- 29951162
TI - Learning and engagement through natural history museums.
AB - This review examines how natural history museums (NHMs) can enhance learning and
engagement in science, particularly for school-age students. First, we describe
the learning potential of informal science learning institutions in general, then
we focus on NHMs. We review the possible benefits of interactions between schools
and NHMs, and the potential for NHMs to teach about challenging issues such as
evolution and climate change and to use digital technologies to augment more
traditional artefacts. We conclude that NHMs can provide students with new
knowledge and perspectives, with impacts that can last for years. Through visits
and their on-line presence, NHMs can help students see science in ways that the
school classroom rarely can, with opportunities to meet scientists, explore whole
topic exhibitions, engage with interactive displays and employ digital
technologies both in situ and to support learning in the school science
classroom. Although these interactions have the potential to foster positive
cognitive, affective and social outcomes for students, there is a lack of
reliable measures of the impact of NHM experiences for students. Opportunities to
foster relationships between NHM staff and teachers through professional
development can help articulate shared goals to support students' learning and
engagement.
PMID- 29951163
TI - The Ability of Different Ketohexoses to Alter Apo-A-I Structure and Function In
Vitro and to Induce Hepatosteatosis, Oxidative Stress, and Impaired Plasma Lipid
Profile in Hyperlipidemic Zebrafish.
AB - In the current study, we have tested the nonenzymatic glycation activities of
ketohexoses, such as tagatose and psicose. Although tagatose-treated apoA-I (t-A
I) and psicose-treated apoA-I (p-A-I) exerted more inhibitory activity you cupric
ion-mediated low-density lipoprotein (LDL) oxidation and oxidized LDL (oxLDL)
phagocytosis into macrophage than fructose-treated apoA-I (f-A-I). In the lipid
free state, t-A-I and f-A-I showed more multimerized band without crosslinking.
Since t-A-I lost its phospholipid binding ability, the rHDL formation was not as
successful as f-A-I. However, injecting t-A-I showed more antioxidant activities
in zebrafish embryo under the presence of oxLDL. Three weeks of consumption of
fructose (50% of wt in Tetrabit/4% cholesterol) showed a 14% elevation of serum
triacylglycerol (TG), while tagatose-administered group showed 30% reduction in
serum TG compared to high cholesterol control. Fructose-fed group showed the
biggest area of Oil Red O staining with the intensity as strong as the HCD
control. However, tagatose-consumed group showed much lesser Oil Red O-stained
area with the reduction of lipid accumulation. In conclusion, although tagatose
treatment caused modification of apoA-I, the functional loss was not as much
severe as the fructose treatment in macrophage cell model, zebrafish embryo, and
hypercholesterolemic zebrafish model.
PMID- 29951164
TI - Serum 8-Oxo-dG as a Predictor of Sensitivity and Outcome of Radiotherapy and
Chemotherapy of Upper Gastrointestinal Tumours.
AB - The level of oxidative stress is important in the initiation and progression of
various age-related diseases, such as cancer. The level of oxidative stress may
also play a significant role in cancer patients' response to treatment. We aimed
to investigate whether serum 8-oxo-dG as a marker of oxidative stress is a
predictor of tumour response. We used modified ELISA with a two-step filtration
to analyse 8-oxo-dG in serum. The relationship between 8-oxo-dG levels, tumour
response, and toxicity was studied in 19 oesophageal cancer patients who received
radiotherapy and 16 gastric cancer patients who received chemotherapy. In the
radiotherapy and the merged radio- and chemotherapy groups, the baseline levels
of 8-oxo-dG were significantly lower in responder patients than in nonresponder
patients and the increments after treatment were greater. In comparison with
patients whose serum 8-oxo-dG levels decrease after treatment, patients with
increasing levels had a longer median "progression-free survival." Our results,
although preliminary, suggest that serum levels of 8-oxo-dG may potentially be
used to predict the sensitivity and outcome of radiotherapy and chemotherapy of
upper gastrointestinal tumours. Patients with 8-oxo-dG levels that are low prior
to treatment and subsequently increase after treatment may be more likely to
benefit from the therapy.
PMID- 29951165
TI - Corrigendum to "Perillaldehyde Inhibits AHR Signaling and Activates NRF2
Antioxidant Pathway in Human Keratinocytes".
AB - [This corrects the article DOI: 10.1155/2018/9524657.].
PMID- 29951167
TI - Molecular Mechanisms Underlying Age-Related Ocular Diseases.
PMID- 29951166
TI - Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells
through RAP1 GTPase Prenylation and Cytoprotective Autophagy.
AB - The present study investigated the cytotoxic effects of statins (atorvastatin
(ATR) and simvastatin (SIM), resp.) and methyl-beta-cyclodextrin (MbetaCD), at
their respective IC50 concentrations, on muscle regeneration in the in vitro
model of murine C2C12 myoblasts. Cotreatment with mevalonate (MEV), farnesol
(FOH), geranylgeraniol (GGOH), or water-soluble cholesterol (Chol-PEG) was
employed to determine whether the statin-dependent myotoxicity resulted from the
lower cholesterol levels or the attenuated synthesis of intermediates of
mevalonate pathway. Our findings demonstrated that while GGOH fully reverted the
statin-mediated cell viability in proliferating myoblasts, Chol-PEG exclusively
rescued MbetaCD-induced toxicity in myocytes. Statins caused loss of prenylated
RAP1, whereas the GGOH-dependent positive effect was accompanied by loss of
nonprenylated RAP1. Geranylgeranyltransferases are essential for muscle cell
survival as inhibition with GGTI-286 could not be reversed by GGOH cotreatment.
The increase in cell viability correlated with elevated AKT 1(S463) and GSK
3beta(S9) phosphorylations. Slight increase in the levels of autophagy markers
(Beclin 1, MAP LC-3IIb) was found in response to GGOH cotreatment. Autophagy rose
time-dependently during myogenesis and was inhibited by statins and MbetaCD.
Statins and MbetaCD also suppressed myogenesis and neither nonsterol isoprenoids
nor Chol-PEG could reverse this effect. These results point to GGOH as the
principal target of statin-dependent myotoxicity, whereas plasma membrane
cholesterol deposit is ultimately essential to restore viability of MbetaCD
treated myocytes. Overall, this study unveils for the first time a link found
between the GGOH- and Chol-PEG-dependent reversal of statin- or MbetaCD-mediated
myotoxicity and cytoprotective autophagy, respectively.
PMID- 29951169
TI - Xenobiotics, Oxidative Stress, and Antioxidants.
PMID- 29951168
TI - Relationship of Oxidative Stress, Inflammation, and the Risk of Metabolic
Syndrome in Patients with Oral Cancer.
AB - Oral cancer is the fifth leading cause of cancer death in Taiwan, and the
prevalence of metabolic syndrome (MS) has also increased globally. The purpose of
this study was to investigate the correlations between the components of MS and
oxidative stress and inflammation in patients with oral cancer based on their
areca-nut-chewing habits. Two hundred patients diagnosed with oral cancer were
recruited, and metabolic parameters, oxidative stress, antioxidant enzyme
activities, and inflammatory markers were measured. 63% of the subjects have
concomitant MS. Subjects who had an areca-nut-chewing habit had significantly
higher levels of fasting glucose (p = 0.04), oxidative stress (p = 0.02), and
inflammatory markers (p = 0.02) than those who never chewed. High-density
lipoprotein-cholesterol level (p = 0.03) and superoxidase dismutase activity (p =
0.02) were significantly lower in individuals who had chewed or were currently
chewers. Areca-nut-chewing habit was associated with the increased risks for MS
and hypertriglyceridemia; the components of MS were positively correlated with
oxidative stress and inflammation. In conclusion, patients with oral cancer who
had an areca-nut-chewing habit exhibited higher levels of oxidative stress and
inflammation, which might be related to an increased risk of MS.
PMID- 29951170
TI - Serpentine Supravenous Hyperpigmentation in an HIV Patient Receiving R-CHOP for
DLBCL.
AB - Serpentine supravenous hyperpigmentation (SSH) is a rare vasculo-cutaneous entity
that has been associated with peripheral infusion of chemotherapy agents, in
particular 5-FU1-3, but also seen with docetaxel4,5, fotemustine6, and
vinorelbine7. It consists of a marked hyperpigmentation along the superficial
network of veins proximal to the chemotherapy infusion site and was originally
described in a 1976 case report in association with 5-FU1. Here, for the first
time, we report SSH in association with R-CHOP chemotherapy.
PMID- 29951171
TI - A Study on the Clinical Outcome of Abiraterone Acetate in Castration Resistant
Prostate Cancer Patients.
AB - Background: Abiraterone acetate was approved by FDA and EMA in April and
September 2011, respectively for treatment of patients with casteration resistant
prostate cancer and those previously treated with docetaxel. It is a selective
inhibitor of androgen biosynthesis which potentially and irreversibly blocks
CYP17, a crucial enzyme in oestrogen and testosterone synthesis. Materials and
Methods: This retrospective study was conducted to evaluate the safety and
efficacy of abiraterone acetate in the treatment of castration resistant prostate
cancer patients. Twenty-two male patients diagnosed with CRPC and experienced
treatment failure with one or more lines of treatment (hormonal manipulation or
chemotherapy) were selected and administered abiraterone acetate (1,000 mg daily)
along with prednisone (5 mg twice daily). Results: Out of 22 patients, 32% had a
good response in reduction of PSA values, while 22% had progression in disease
and 45% had a stable disease. Potassium, Haemoglobin, and serum sreatinine levels
were not affected by the drug. Due to severe GI intolerance, the drug had to be
stopped for one patient. The results of this study showed that abiraterone
acetate significantly lowered the PSA values and prolonged progression- free
survival in metastatic castration resistant prostate cancer patients who had
progressed after first-line or second-line treatment. The overall average median
survival and the median duration of drug exposure for CRPC who received AA was
found to be 11.1 months [range 3-18]. Since AA plus prednisolone are available as
oral dosage forms, they can be given in outpatient setting. Conclusion:
Abiraterone acetate is a drug of choice for CRPC and also for those who had
previously received one or two chemotherapy regimens. Since it is a new
therapeutic regimen, this study included small sample size, but there are a few
studies indicating the therapeutic efficacy of AA among patients with castration
resistant prostate cancer.
PMID- 29951172
TI - Multiple Cranial Nerve Palsy Concomitant with Leptomeningeal Involvement in
Multiple Myeloma: A Case Report and Review of Literature.
AB - Neurologic symptoms are quite common in multiple myeloma, but direct invasion of
central nervous system is extremely rare. Leptomeningeal multiple myeloma, as a
rare neurological manifestation of multiple myeloma, presents with impairment of
consciousness, cranial nerve palsies and convulsions. Here, we describe a 52-year
old male patient, known case of multiple myeloma, who presented with bilateral
visual loss and difficulty in swallowing.
PMID- 29951173
TI - Association between Altered Expression and Genetic Variations of Transforming
Growth Factor beta-Smad Pathway with Chronic Myeloid Leukemia.
AB - Background: Chronic myeloid leukemia (CML) is a hematological disorder caused by
fusion of BCR and ABL genes. BCR-ABL dependent and independent pathways play
equally important role in CML. TGFbeta-Smad pathway, an important BCR -ABL
independent pathway, has scarce data in CML. Present study investigate the
association between TGFbeta-Smad pathway and CML. Materials and Methods: Sixty
four CML patients and age matched healthy controls (n=63) were enrolled in this
study. Patients were segregated into responder and resistant groups depending on
their response to Imatinib mesylate (IM). TGFbeta1 serum levels were evaluated by
ELISA and transcript levels of TGFbeta1 receptors, SMAD4 and SMAD7 were evaluated
by Real-Time PCR. Sequencing of exons and exon-intron boundaries of study genes
was performed using Next Generation Sequencing (NGS) in 20 CML patients.
Statistical analysis was performed using SPSS version 16.0. Results:TGFbeta1
serum levels were significantly elevated (p = 0.02) and TGFbetaR2 and SMAD4 were
significantly down-regulated (p = 0.012 and p = 0.043 respectively) in the
patients. c.69A>G in TGFbeta1, c.1024+24G>A in TGFbetaR1 and g.46474746C>T in
SMAD7 were the most important genetic variants observed with their presence in
10/20, 8/20 and 7/20 patients respectively. In addition, TGFbetaR1 transcript
levels were reduced in CML patients with c.69A>G mutation. None of the genes
differed significantly in terms of expression or genetic variants between
responder and resistant patient groups. Conclusion: Our findings demonstrate the
role of differential expression and genetic variants of TGFbeta-Smad pathway in
CML. Decreased TGFbetaR2 and SMAD4 levels observed in the present study may be
responsible for reduced tumor suppressive effects of this pathway in CML.
PMID- 29951174
TI - Pattern of Kebab Intake as a Potential Carcinogenic Risk Factor in Adults of
Kermanshah, Iran: 2015.
AB - Background: Epidemiologic studies indicated that dietary pattern plays a
determinant role in cancer incidence. They also indicated that 1/3 of cancers are
associated to foods. Diet contains different carcinogenic agents: naturally
occurring chemicals, synthetic components and compounds produced during cooking
such as kebab. This traditional food is one of the most popular foods in the
Middle East, particularly in Iran. Red meat, especially lamb or veal, is the most
common meat used in preparation of kebab. Since kebab is considered as a food
containing carcinogenic compounds, so the purpose of this study was to assess the
consumption pattern of kebab in a sample of Iranian adults and its relationship
with demographic characteristics. Materials and Methods: This cross-sectional
study was conducted between March and April 2015 on 705 Iranian adults who were
living in Kermanshah province in the west of Iran. Subjects were selected
randomly from different districts of Kermanshah. Data were collected through a
questionnaire survey which had been designed by academic members of Department of
Nutrition at Kermanshah University of Medical Sciences. Data analysis was
performed using SPSS Version 20. The results were expressed as mean +/- SD.
Student's t-test, ANOVA and chi-square tests were performed to compare the study
groups. The normality of data was assessed using the Kolmogorov-Smirnov test. All
results were analyzed using a significance level of P <0.05. Results: The results
indicated that nearly 60% of subjects have a high tendency to consume kebab. The
average of kebab consumption among the participants in this study was 4 times per
month. Nearly, 85% of study participants tended to consume kebab with a large
amount of salt. The chi-square test determined the significant difference between
education and tendency to consume kebab; individuals with higher level of
education had more tendency to consume kebab than those having lower level of
education (p=0.021). In this study, 93.9% of participants used charcoal, a
cooking fuel, to prepare kebab. Conclusion: The results of this study point out
that the study participants, regardless of socio-economic status, consume high
amounts of kebab, and thus this unhealthy eating habit will increase the risk of
carcinogenesis. Therefore, the immediate attention of Public Health Officials is
required.
PMID- 29951175
TI - Utility of a Single-Tube, Six-Color Flow Cytometry Panel for the Diagnosis of
Myelodysplastic Syndrome: Experience of a Tertiary Care Centre in India.
AB - Background: Diagnosis of myelodysplastic syndromes (MDS) is challenging in the
presence of morphological mimickers. Flow cytometric immunophenotyping (FCI) has
been added to the diagnostic armamentarium, but its use in clinical practice is
variable. Materials and Methods: Bone marrow aspirate samples from 54 patients
with a clinical and/or morphological suspicion of MDS were subjected to FCI using
a single-tube, 6-colour panel comprising of monoclonal antibodies against CD13,
CD11b, CD16, CD34, CD45 and CD56. Analysis was centered on the abnormal
maturation pattern of granulocytes, blast percentage (>=3%) and ratio of side
scatter peak channel value (SSC-PCV) of granulocytes and lymphocytes. Each of
these parameters was assigned a score of 1. Overall sensitivity and specificity
of this panel was ascertained to differentiate cytopenia/s of MDS from non-MDS
cases. Results: Forty MDS and 14 non-MDS cases were diagnosed based on morphology
and cytogenetic results. Twenty control samples were also processed
simultaneously for FCI to assign the cutoff for various flow cytometric
parameters. A score >=2 was defined as positive for MDS. Hypogranularity was
present in 62.5% cases of MDS. The median SSC-PCV of granulocytes and lymphocytes
was 6.16 in the MDS group, 7.9 in the non-MDS group and 8.90 in the control group
(p <0.05). This cut-off value of 6.16 had a specificity of 92.5% based on the ROC
curve analysis. Abnormal granulocyte maturation patterns for CD13/16, CD13/11b
and CD11b/16 dot plots were observed in 95.3, 69.8 and 74.4% cases, respectively.
The overall sensitivity and specificity of the panel was found to be 87.5% and
64.2%, respectively. Conclusion: FCI is now an important tool for diagnostic
workup in patients presenting with persistent cytopenia with or without
morphological evidence of dyspoiesis. Inclusion of objective parameters like SSC
PCV would also reduce inter-lab variability in MDS diagnosis.
PMID- 29951176
TI - Comparative Evaluation of Biochemical and Hematological Parameters of Pre-Storage
Leukoreduction during RBC Storage.
AB - Background: Some of the red cell storage lesions (RCSLs) take place during red
blood cell (RBC) storage and may reduce the function of these cells dramatically,
which mostly caused by residual leucocytes in blood components. This study was
planned to observe the biochemical and hematological changes in pre-storage
leukoreduced RBC (LR-RBC) compared with unfiltered RBC during in vitro storage.
Materials and Methods: Ten unit RBCs were collected, processed and stored
according to Iranian standard operating procedure (SOP) of Iranian Blood
Transfusion Organization (IBTO). Every unit was split into two equal parts,
unfiltered RBC and LR-RBC. Samples were collected and tested on weeks of storage.
Biochemical parameters such as lactate dehydrogenase (LDH), lactate concentration
and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity were measured by
auto-analyzer. In addition, hematology analyzer was used to monitor the change of
RBC indices such as (MCV), (MCH) and (MCHC). Results: In this study, both groups
showed progressive increase of LDH and lactate levels, and also G6PD activity
decreased during storage. Mean of LDH and lactate in unfiltered RBC was
significantly increased compared with LR-RBC during all days of storage (p<
0.05). There was statically significant decrease in the G6PD enzyme activity
between the two groups and weeks of storage (p< 0.05). However, the RBC indices
remained within the expected levels in both groups. Conclusion: LR-RBC and RBC
both exhibited RCSL during storage, but LR-RBC is effective in reducing Red cell
storage lesion (RCSL) and also improves the quality of stored red blood cells.
PMID- 29951177
TI - Study of the Relationship between HPA-1 and HPA-5 Gene Polymorphisms and
Refractory to Platelet Therapy and Recombinant Factor VII in Glanzmann
Thrombasthenia Patients in Southeast of Iran.
AB - Background: Glanzmann Thrombasthenia (GT) is a rare autosomal disease. HPA (Human
Platelet Alloantigen) is a surface polymorphic alloantigen of platelets. This
study was intended to investigate and compare the polymorphism of HPA-1 and HPA-5
genes in two groups of GT patients, with and without resistance to platelet and
recombinant factor VII therapy. Materials and Methods: This case control study
was performed on GT patients (n=16) with resistance to platelet therapy and
recombinant factor VII and control group of GT patients (n=16) without resistance
to platelet therapy and recombinant factor VII. The consent form was completed by
each patient. Gene polymorphisms of HPA-1 and HPA-5 were investigated using SSP
PCR, and the obtained data were analyzed using statistical software SPSS16.0.
Results: The results indicated no significant relationship between the studied
genes and their resistance to platelet therapy and recombinant factor VII. The
frequencies of HPA-1 genotype a/a were 98% and 94% in patient and control groups,
respectively. The frequency of allele b was found to be less than allele a. The
value of this allele was 4% in patient group and 1% in control group. In
addition, the HPA-5a/a (98%) was the most frequent alloantigen?? (check it) in
both groups. Seven percent (7%) of the patients had the HPA-5a/b genotype, and
the HPA-5b/b was found to be absent in these individuals. Conclusion: According
to the results obtained, it could be concluded that these genes play no role in
resistance to platelet therapy.
PMID- 29951178
TI - Association between (GT)n Repeats in Heme Oxygenase-1 Gene Promoter and 3-Year
Survival of Patients with Acute Leukemia: a Controlled, Cross-Sectional Study.
AB - Background: Acute leukemia is a common pediatric cancer. Novel strategies for
treatment of acute leukemia have been developed, but treatment resistance is
remained as the most problematic issue. It is hypothesized that the HO-1 gene up
regulation is responsible for tumor resistance to chemotherapy or radiotherapy
induced apoptosis. The levels of HO-1 expression are related to (GT)n
microsatellite polymorphisms in the location of its promoter. This study designed
to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene
between acute leukemia patients and healthy controls. Indeed, 3-year disease-free
survival was also evaluated. Methods: Sixty-three patients with acute leukemia
and seventy healthy infants were included in this study. We used the medical
records of patients to collect information about survival after chemotherapy. The
number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer.
Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in
both cases and controls. Children with longer alleles ((GT)n >= 27) had enhanced
3-year survival rate after treatment with chemotherapy or radiotherapy (P<0.05).
Conclusion: Although no significant differences were observed between leukemia
patients and controls regarding allelic frequency, we found elevated frequency of
"LL" genotype in leukemia patients with good prognosis and 3-year surveillance.
Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with
subsequent increased resistance of leukemia patients to therapy.
PMID- 29951179
TI - Assessing Prognostic Factors in Hodgkin's Lymphoma: Multistate Illness-Death
Model.
AB - Background: Hodgkin's lymphoma (HL) is a unique cancer of lymphocytes that has
unknown reason. As lymphocytes are found throughout the lymphatic system, HL can
start almost anywhere in the body. It usually starts in a group of lymph nodes in
one part of the body; it usually spreads in a predictable form, from one group of
lymph nodes to the next. Eventually, it can spread to almost any tissue or organ
in the body through the lymphatic system or the bloodstream. So it's important to
evaluate the prognostic factors of mortality and recurrence. The aim of this
study is to use multistate model to consider the event history of patients and
assess important prognostic factors. Materials and Methods: We performed a
retrospective review on 389 patients with Hodgkin's disease referred to the
Oncology and Hematology Center, Shafa Hospital, Ahvaz during 2002 and 2012. An
illness - death model was fitted to assess the hazard of transitions during the
course of the disease for each prognostic factor. Results: The results showed
that the prevalence rate was higher in male population >=50 years of age with a
hemoglobin level of less than 10.5 g per deciliter and diagnosis of advanced
stage of disease. The risk of death for males was twice more than females
(HR=2.07). Moreover, patients with mediastina and spleen involvement were more
than others in danger of death (1.66 and 1.36, respectively). Conclusion: In
conclusion, the multistate model offers an appropriate method to consider the
event history of patients and determine main prognostic factors, which play an
important role in rapid diagnosis and choosing the best treatment choice for each
patient.
PMID- 29951180
TI - Clear Cell Sarcoma: A Case Report and Review of Literature.
AB - Clear cell sarcoma (CCS), a deep-rooted tumor with a predilection for lower
extremities, has a proclivity to involve the tendons and aponeuroses. This
sarcoma is seen predominantly around the foot and ankle region. Diagnosis is
mainly finalized using histological and immunohistochemical assessment. The main
treatment strategy is surgery followed by chemotherapy. An erratic challenge is
posed by histological similarity and immunohistochemical overlap to the diagnosis
and distinguishing of clear cell sarcoma from primary or metastatic malignant
melanoma (MM) which is more common. Here, we described a CCS case located in the
left leg of a 37-year-old male patient.
PMID- 29951181
TI - Predictors and Correlates of Fatigue in Sickle Cell Disease Patients.
AB - Background: Although fatigue is the most important symptom of Sickle Cell
Disease, the extent of it is unknown, and causal mechanisms are not well
understood. This article explores biopsychosocial characteristics that can
potentially contribute to fatigue in SCD. Materials and Methods: This cross
sectional, correlational study included 97 SCD patients who aged over 16 years
and had records in Thalassemia Ward and Clinic of Shafa Hospital affiliated to
Ahvaz University of Medical Sciences, Ahvaz, Iran. Data were collected from a
self- reported demographic questionnaire, measuring depression, anxiety stress
scale (DASS-21) and fatigue severity scale (FSS). Data analysis was done by
descriptive statistics, independent sample t-tests, Pearson's correlation
coefficient, one-way ANOVA and multiple stepwise regression. Results: More than
50% of study participants were mostly single women. A majority of patients had a
diagnosis of HgbSS disease. Levels of depression, anxiety and stress were severe
in more than half of the participants. About 65% of SCD patients reported signs
of fatigue. Moreover, fatigue, depression, anxiety and stress had a high
intercorrelation. Depression, blood transfusion, renal diseases and work status
were predictors of fatigue according to the models used in this survey.
Conclusion: The results of the study indicated that SCD patients who had
depression, blood transfusions, SCD-related renal complications, students and
working people experienced more fatigue. So, if fatigue is present, it is
important to recognize the existence of these conditions or vice versa. Routine
assessment and improved management of fatigue, effective interventions to reduce
fatigue, are highly recommended for patients with SCD.
PMID- 29951182
TI - A Framework of Rebalancing Imbalanced Healthcare Data for Rare Events'
Classification: A Case of Look-Alike Sound-Alike Mix-Up Incident Detection.
AB - Identifying rare but significant healthcare events in massive unstructured
datasets has become a common task in healthcare data analytics. However,
imbalanced class distribution in many practical datasets greatly hampers the
detection of rare events, as most classification methods implicitly assume an
equal occurrence of classes and are designed to maximize the overall
classification accuracy. In this study, we develop a framework for learning
healthcare data with imbalanced distribution via incorporating different
rebalancing strategies. The evaluation results showed that the developed
framework can significantly improve the detection accuracy of medical incidents
due to look-alike sound-alike (LASA) mix-ups. Specifically, logistic regression
combined with the synthetic minority oversampling technique (SMOTE) produces the
best detection results, with a significant 45.3% increase in recall (recall =
75.7%) compared with pure logistic regression (recall = 52.1%).
PMID- 29951183
TI - Symptom severity in autism spectrum disorder is related to the frequency and
severity of nausea and vomiting during pregnancy: a retrospective case-control
study.
AB - Background: Nausea and vomiting during pregnancy (NVP) is thought to be caused by
changes in maternal hormones during pregnancy. Differences in hormone exposure
during prenatal life have been implicated in the causal pathways for some cases
of autism spectrum disorder (ASD). However, no study has investigated whether the
presence and severity of NVP may be related to symptom severity in offspring with
ASD. Methods: A large sample of children with ASD (227 males and 60 females, aged
2 to 18 years) received a clinical assessment, during which parents completed
questionnaires regarding their child's social (Social Responsiveness Scale, SRS)
and communication (Children's Communication Checklist-2nd edition, CCC-2)
symptoms. Parents also reported on a 5-point scale the frequency and severity of
NVPs during the pregnancy of the child being assessed: (1) no NVP during the
pregnancy, (2) occasional nausea, but no vomiting, (3) daily nausea, but no
vomiting, (4) occasional vomiting, with or without nausea, and (5) daily nausea
and vomiting. Results: Impairments in social responsiveness in offspring, as
indexed by SRS total score, significantly increased as a function of the
frequency and severity of their mothers' NVP, as did the level of language
difficulties as indexed by the Global Communication Composite of the CCC-2.
Conclusions: The strong, positive association between increasing frequency and
severity of NVP and ASD severity in offspring provides further evidence that
exposure to an atypical hormonal environment during prenatal life may affect
neurodevelopment and contribute to the ASD phenotype. Given that the measure of
NVP symptoms in the current study was based on retrospective recall, replication
of this finding is required before strong conclusions can be drawn.
PMID- 29951184
TI - Role of miR-146a in neural stem cell differentiation and neural lineage
determination: relevance for neurodevelopmental disorders.
AB - Background: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene
expression at the post-transcriptional level. miRNAs have emerged as important
modulators of brain development and neuronal function and are implicated in
several neurological diseases. Previous studies found miR-146a upregulation is
the most common miRNA deregulation event in neurodevelopmental disorders such as
autism spectrum disorder (ASD), epilepsy, and intellectual disability (ID). Yet,
how miR-146a upregulation affects the developing fetal brain remains unclear.
Methods: We analyzed the expression of miR-146a in the temporal lobe of ASD
children using Taqman assay. To assess the role of miR-146a in early brain
development, we generated and characterized stably induced H9 human neural stem
cell (H9 hNSC) overexpressing miR-146a using various cell and molecular biology
techniques. Results: We first showed that miR-146a upregulation occurs early
during childhood in the ASD brain. In H9 hNSC, miR-146a overexpression enhances
neurite outgrowth and branching and favors differentiation into neuronal like
cells. Expression analyses revealed that 10% of the transcriptome was deregulated
and organized into two modules critical for cell cycle control and neuronal
differentiation. Twenty known or predicted targets of miR-146a were significantly
deregulated in the modules, acting as potential drivers. The two modules also
display distinct transcription profiles during human brain development, affecting
regions relevant for ASD including the neocortex, amygdala, and hippocampus. Cell
type analyses indicate markers for pyramidal, and interneurons are highly
enriched in the deregulated gene list. Up to 40% of known markers of newly
defined neuronal lineages were deregulated, suggesting that miR-146a could
participate also in the acquisition of neuronal identities. Conclusion: Our
results demonstrate the dynamic roles of miR-146a in early neuronal development
and provide new insight into the molecular events that link miR-146a
overexpression to impaired neurodevelopment. This, in turn, may yield new
therapeutic targets and strategies.
PMID- 29951186
TI - Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in
Parkinson's Disease: A Meta-Analysis.
AB - Bilateral deep brain stimulation of subthalamic nucleus (STN-DBS) has proven
effective in improving motor symptoms in Parkinson's disease (PD) patients.
However, psychiatric changes after surgery are controversial. In this study, we
specifically analyzed apathy following bilateral STN-DBS in PD patients using a
meta-analysis. Relevant articles utilized for this study were obtained through
literature search on PubMed, ScienceDirect, and Embase databases. The articles
included were those contained both pre- and postsurgery apathy data acquired
using the Starkstein Apathy Scale or Apathy Evaluation Scale with patient follow
up of at least three months. A total of 9 out of 86 articles were included in our
study through this strict screening process. Standardized mean difference (SMD),
that is, Cohen's d, with a 95% confidence interval (CI) was calculated to show
the change. We found a significant difference between the presurgery stage and
the postsurgery stage scores (SMD = 0.35, 95% CI: 0.17~0.52, P < 0.001). STN-DBS
seems to relatively worsen the condition of apathy, which may result from both
the surgery target (subthalamic nucleus) and the reduction of dopaminergic
medication. Further studies should focus on the exact mechanisms of possible
postoperative apathy in the future.
PMID- 29951187
TI - Spiking neural networks for computer vision.
AB - State-of-the-art computer vision systems use frame-based cameras that sample the
visual scene as a series of high-resolution images. These are then processed
using convolutional neural networks using neurons with continuous outputs.
Biological vision systems use a quite different approach, where the eyes
(cameras) sample the visual scene continuously, often with a non-uniform
resolution, and generate neural spike events in response to changes in the scene.
The resulting spatio-temporal patterns of events are then processed through
networks of spiking neurons. Such event-based processing offers advantages in
terms of focusing constrained resources on the most salient features of the
perceived scene, and those advantages should also accrue to engineered vision
systems based upon similar principles. Event-based vision sensors, and event
based processing exemplified by the SpiNNaker (Spiking Neural Network
Architecture) machine, can be used to model the biological vision pathway at
various levels of detail. Here we use this approach to explore structural
synaptic plasticity as a possible mechanism whereby biological vision systems may
learn the statistics of their inputs without supervision, pointing the way to
engineered vision systems with similar online learning capabilities.
PMID- 29951185
TI - Autism spectrum disorder: prospects for treatment using gene therapy.
AB - Autism spectrum disorder (ASD) is characterised by the concomitant occurrence of
impaired social interaction; restricted, perseverative and stereotypical
behaviour; and abnormal communication skills. Recent epidemiological studies have
reported a dramatic increase in the prevalence of ASD with as many as 1 in every
59 children being diagnosed with ASD. The fact that ASD appears to be principally
genetically driven, and may be reversible postnatally, has raised the exciting
possibility of using gene therapy as a disease-modifying treatment. Such
therapies have already started to seriously impact on human disease and
particularly monogenic disorders (e.g. metachromatic leukodystrophy, SMA type 1).
In regard to ASD, technical advances in both our capacity to model the disorder
in animals and also our ability to deliver genes to the central nervous system
(CNS) have led to the first preclinical studies in monogenic ASD, involving both
gene replacement and silencing. Furthermore, our increasing awareness and
understanding of common dysregulated pathways in ASD have broadened gene
therapy's potential scope to include various polygenic ASDs. As this review
highlights, despite a number of outstanding challenges, gene therapy has
excellent potential to address cognitive dysfunction in ASD.
PMID- 29951188
TI - Colour and illumination in computer vision.
AB - In computer vision, illumination is considered to be a problem that needs to be
'solved'. The colour cast due to illumination is removed to support colour-based
image recognition and stable tracking (in and out of shadows), among other tasks.
In this paper, I review historical and current algorithms for illumination
estimation. In the classical approach, the illuminant colour is estimated by an
ever more sophisticated analysis of simple image summary statistics often
followed by a bias correction step. Bias correction is a function applied to the
estimates made by a given illumination estimation algorithm to correct consistent
errors in the estimations. Most recently, the full power, and much higher
complexity, of deep learning has been deployed (where, effectively, the
definition of the image statistics of interest and the type of analysis carried
out are found as part of an overall optimization). In this paper, I challenge the
orthodoxy of deep learning, i.e. that it is the best approach for illuminant
estimation. We instead focus on the final bias correction stage found in many
simple illumination estimation algorithms. There are two key insights in our
method. First, we argue that the bias must be corrected in an exposure invariant
way. Second, we show that this bias correction amounts to 'solving for a
homography'. Homography-based illuminant estimation is shown to deliver leading
illumination estimation performance (at a very small fraction of the complexity
of deep learning methods).
PMID- 29951189
TI - Control of gaze in natural environments: effects of rewards and costs,
uncertainty and memory in target selection.
AB - The development of better eye and body tracking systems, and more flexible
virtual environments have allowed more systematic exploration of natural vision
and contributed a number of insights. In natural visually guided behaviour,
humans make continuous sequences of sensory-motor decisions to satisfy current
goals, and the role of vision is to provide the relevant information in order to
achieve those goals. This paper reviews the factors that control gaze in natural
visually guided actions such as locomotion, including the rewards and costs
associated with the immediate behavioural goals, uncertainty about the state of
the world and prior knowledge of the environment. These general features of human
gaze control may inform the development of artificial systems.
PMID- 29951190
TI - Rotation invariant visual processing for spatial memory in insects.
AB - Visual memory is crucial to navigation in many animals, including insects. Here,
we focus on the problem of visual homing, that is, using comparison of the view
at a current location with a view stored at the home location to control movement
towards home by a novel shortcut. Insects show several visual specializations
that appear advantageous for this task, including almost panoramic field of view
and ultraviolet light sensitivity, which enhances the salience of the skyline. We
discuss several proposals for subsequent processing of the image to obtain the
required motion information, focusing on how each might deal with the problem of
yaw rotation of the current view relative to the home view. Possible solutions
include tagging of views with information from the celestial compass system,
using multiple views pointing towards home, or rotation invariant encoding of the
view. We illustrate briefly how a well-known shape description method from
computer vision, Zernike moments, could provide a compact and rotation invariant
representation of sky shapes to enhance visual homing. We discuss the biological
plausibility of this solution, and also a fourth strategy, based on observed
behaviour of insects, that involves transfer of information from visual memory
matching to the compass system.
PMID- 29951191
TI - Not-So-CLEVR: learning same-different relations strains feedforward neural
networks.
AB - The advent of deep learning has recently led to great successes in various
engineering applications. As a prime example, convolutional neural networks, a
type of feedforward neural network, now approach human accuracy on visual
recognition tasks like image classification and face recognition. However, here
we will show that feedforward neural networks struggle to learn abstract visual
relations that are effortlessly recognized by non-human primates, birds, rodents
and even insects. We systematically study the ability of feedforward neural
networks to learn to recognize a variety of visual relations and demonstrate that
same-different visual relations pose a particular strain on these networks.
Networks fail to learn same-different visual relations when stimulus variability
makes rote memorization difficult. Further, we show that learning same-different
problems becomes trivial for a feedforward network that is fed with perceptually
grouped stimuli. This demonstration and the comparative success of biological
vision in learning visual relations suggests that feedback mechanisms such as
attention, working memory and perceptual grouping may be the key components
underlying human-level abstract visual reasoning.
PMID- 29951192
TI - The perception of colour and material in naturalistic tasks.
AB - Perceived object colour and material help us to select and interact with objects.
Because there is no simple mapping between the pattern of an object's image on
the retina and its physical reflectance, our perceptions of colour and material
are the result of sophisticated visual computations. A long-standing goal in
vision science is to describe how these computations work, particularly as they
act to stabilize perceived colour and material against variation in scene factors
extrinsic to object surface properties, such as the illumination. If we take
seriously the notion that perceived colour and material are useful because they
help guide behaviour in natural tasks, then we need experiments that measure and
models that describe how they are used in such tasks. To this end, we have
developed selection-based methods and accompanying perceptual models for studying
perceived object colour and material. This focused review highlights key aspects
of our work. It includes a discussion of future directions and challenges, as
well as an outline of a computational observer model that incorporates early,
known, stages of visual processing and that clarifies how early vision shapes
selection performance.
PMID- 29951194
TI - Accurate and robust localization for walking robots fusing kinematics, inertial,
vision and LIDAR.
AB - In this article, we review methods for localization and situational awareness of
biped and quadruped robotics. This type of robot is modelled as a free-floating
mechanical system subject to external forces and constrained by whole-body
distributed rigid contacts. Measurements of the state of the robot can be made
using a variety of sensor information-such as kinematics (the sensing of the
joint angles of the robot), contact force (pressure sensors in the robot's feet),
accelerometers and gyroscopes as well as external sensors such as vision and
LIDAR. This high-frequency state estimate is then passed to the control system of
the robot to allow it to traverse terrain or manipulate its environment. In this
article, we describe the development of an estimator for the Boston Dynamics
Atlas humanoid robot. It was later adapted to the HyQ2 quadruped, developed by
the Istituto Italiano di Tecnologia. Some discussion is given as to future trends
while also considering briefly the relationship with biological systems.
PMID- 29951193
TI - The functional neuroanatomy of face perception: from brain measurements to deep
neural networks.
AB - A central goal in neuroscience is to understand how processing within the ventral
visual stream enables rapid and robust perception and recognition. Recent
neuroscientific discoveries have significantly advanced understanding of the
function, structure and computations along the ventral visual stream that serve
as the infrastructure supporting this behaviour. In parallel, significant
advances in computational models, such as hierarchical deep neural networks
(DNNs), have brought machine performance to a level that is commensurate with
human performance. Here, we propose a new framework using the ventral face
network as a model system to illustrate how increasing the neural accuracy of
present DNNs may allow researchers to test the computational benefits of the
functional architecture of the human brain. Thus, the review (i) considers
specific neural implementational features of the ventral face network, (ii)
describes similarities and differences between the functional architecture of the
brain and DNNs, and (iii) provides a hypothesis for the computational value of
implementational features within the brain that may improve DNN performance.
Importantly, this new framework promotes the incorporation of neuroscientific
findings into DNNs in order to test the computational benefits of fundamental
organizational features of the visual system.
PMID- 29951195
TI - Correction to 'Crafting of functional biomaterials by directed molecular self
assembly of triple helical peptide building blocks'.
AB - [This corrects the article DOI: 10.1098/rsfs.2016.0138.].
PMID- 29951196
TI - Colour, contours, shading and shape: flow interactions reveal anchor
neighbourhoods.
AB - Two dilemmas arise in inferring shape information from shading. First, depending
on the rendering physics, images can change significantly with (even) small
changes in lighting or viewpoint, while the percept frequently does not. Second,
brightness variations can be induced by material effects-such as pigmentation-as
well as by shading effects. Improperly interpreted, material effects would
confound shading effects. We show how these dilemmas are coupled by reviewing
recent developments in shape inference together with a role for colour in
separating material from shading effects. Aspects of both are represented in a
common geometric (flow) framework, and novel displays of hue/shape interaction
demonstrate a global effect with interactions limited to localized regions. Not
all parts of an image are perceptually equal; shape percepts appear to be
constructed from image anchor regions.
PMID- 29951197
TI - Image interpretation above and below the object level.
AB - Computational models of vision have advanced in recent years at a rapid rate,
rivalling in some areas human-level performance. Much of the progress to date has
focused on analysing the visual scene at the object level-the recognition and
localization of objects in the scene. Human understanding of images reaches a
richer and deeper image understanding both 'below' the object level, such as
identifying and localizing object parts and sub-parts, as well as 'above' the
object level, such as identifying object relations, and agents with their actions
and interactions. In both cases, understanding depends on recovering meaningful
structures in the image, and their components, properties and inter-relations, a
process referred here as 'image interpretation'. In this paper, we describe
recent directions, based on human and computer vision studies, towards human-like
image interpretation, beyond the reach of current schemes, both below the object
level, as well as some aspects of image interpretation at the level of meaningful
configurations beyond the recognition of individual objects, and in particular,
interactions between two people in close contact. In both cases the recognition
process depends on the detailed interpretation of so-called 'minimal images', and
at both levels recognition depends on combining 'bottom-up' processing,
proceeding from low to higher levels of a processing hierarchy, together with
'top-down' processing, proceeding from high to lower levels stages of visual
analysis.
PMID- 29951198
TI - A new approach to solving the feature-binding problem in primate vision.
AB - We discuss a recently proposed approach to solve the classic feature-binding
problem in primate vision that uses neural dynamics known to be present within
the visual cortex. Broadly, the feature-binding problem in the visual context
concerns not only how a hierarchy of features such as edges and objects within a
scene are represented, but also the hierarchical relationships between these
features at every spatial scale across the visual field. This is necessary for
the visual brain to be able to make sense of its visuospatial world. Solving this
problem is an important step towards the development of artificial general
intelligence. In neural network simulation studies, it has been found that
neurons encoding the binding relations between visual features, known as binding
neurons, emerge during visual training when key properties of the visual cortex
are incorporated into the models. These biological network properties include (i)
bottom-up, lateral and top-down synaptic connections, (ii) spiking neuronal
dynamics, (iii) spike timing-dependent plasticity, and (iv) a random distribution
of axonal transmission delays (of the order of several milliseconds) in the
propagation of spikes between neurons. After training the network on a set of
visual stimuli, modelling studies have reported observing the gradual emergence
of polychronization through successive layers of the network, in which
subpopulations of neurons have learned to emit their spikes in regularly
repeating spatio-temporal patterns in response to specific visual stimuli. Such a
subpopulation of neurons is known as a polychronous neuronal group (PNG). Some
neurons embedded within these PNGs receive convergent inputs from neurons
representing lower- and higher-level visual features, and thus appear to encode
the hierarchical binding relationship between features. Neural activity with this
kind of spatio-temporal structure robustly emerges in the higher network layers
even when neurons in the input layer represent visual stimuli with spike timings
that are randomized according to a Poisson distribution. The resulting
hierarchical representation of visual scenes in such models, including the
representation of hierarchical binding relations between lower- and higher-level
visual features, is consistent with the hierarchical phenomenology or subjective
experience of primate vision and is distinct from approaches interested in
segmenting a visual scene into a finite set of objects.
PMID- 29951199
TI - C-reactive protein and hepatocellular carcinoma: analysis of its relationships to
tumor factors.
AB - C-reactive protein (CRP) is a blood marker for inflammation and is an independent
prognostic factor for many human cancers. Combined with albumin levels, it forms
the basis of the Glasgow Index for cancer prognosis. We reviewed the literature
on CRP and HCC and also evaluated blood CRP levels and combination CRP plus
albumin levels in a large HCC cohort. In order to understand the prognostic
significance of CRP, we retrospectively examined a large HCC cohort and examined
the relationship of CRP levels to tumor parameters. We report, that CRP alone and
CRP plus albumin combined as well, significantly correlated with parameters of
HCC aggressiveness, such as maximum tumor dimension (MTD), portal vein thrombosis
(PVT) and blood alpha-fetoprotein (AFP) levels, both as individual parameters and
all parameters together (Aggressiveness Index). This extends current thinking, to
suggest a possible explanation for the usefulness of blood CRP levels in HCC
prognostication.
PMID- 29951200
TI - NICD-mediated notch transduction regulates the different fate of chicken
primordial germ cells and spermatogonial stem cells.
AB - Background: Notch signaling is mainly regulated by Notch1 during development of
chicken germ stem cells; however, the molecular mechanisms that contribute to
generation of these germ stem cells have not been thoroughly investigated.
Results: In our studies, Overexpression of the Notch1 NICD promoted development
of the reproductive ridge, but inhibited the formation of seminiferous tubules.
The formation efficiency of PGCs in the reproductive ridge following
overexpression of NICD (7.5% +/- 0.11) was significantly higher than that (4.9%
+/- 0.17, p < 0.05) following inhibition of NICD, While the formation efficiency
of spermatogonial stem cells (SSCs) in the testes (12.7% +/- 0.08) was
significantly lower after NICD overexpression than that after inhibition of NICD
(16.3% +/- 0.16, p < 0.05). Using co-immunoprecipitation, we found that this
anomaly stemmed from the reversal of dissociation of the Notch-regulated
transcription factor CBF-1/RBP co-suppression complex during the differentiation
of PGCs into SSCs. This dissociation of the CBF-1/RBP co-suppressing complex
during the differentiation of ESCs into PGCs resulted in the release of HDAC1 and
HDAC2 and the recruitment of mastermind-like 1 to form a coactive complex to
promote the expression of the downstream transcription suppressor hairy/enhancer
of split-1. Dynamic expression of transducin-like enhancer of split 3, TLE4, and
C-terminal binding protein 2 during further differentiation of PGCs inhibited the
dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression
of the downstream genes. Conclusions: In summary, Notch signaling plays
diametrically opposing roles during normal development of chicken PGCs and SSCs,
and these functions was determined by the expression of NICD, changes in the CBF
1/RBP complex composition, and histone modification.
PMID- 29951201
TI - Biased online media coverage: chiropractic and stroke in google news.
AB - Background: Chiropractic has professional tensions with other medical
disciplines. This sets up a biased online media coverage of controversial issues,
such as the unverified causal relation between chiropractic treatment and stroke.
The objective of this study is to find and analyze recent online media texts
relevant to the alleged causal relation between chiropractic treatment and
stroke, using Google News search, including such characteristics of texts as tone
and position on Google News Search Engine Results Page (SERP). Methods: We built
a research design of quantitative content analysis of online media coverage of
the unverified causal relation between chiropractic treatment and stroke
throughout the year 2015, from January 1 to December 31, using Google News. We
operationalized appropriate frames as keywords inclusive to this relation, to
carry out a comprehensive search for relevant online texts. The collected media
texts were extensively analyzed for frequencies of keywords and locations of
keywords, and for tones as positive, neutral, negative connotation, or negative,
measuring 12 variables on categorical scales. Results: Our search identified a
total of 146 relevant online media texts, corresponding to the frames, which were
all analyzed. The vast majority of identified texts had a negative tone or
connotation, but most were not located on the first search page. Conclusions: The
chiropractic profession is concerned about the biased media coverage of the
unverified causal relation between chiropractic treatment and stroke. However,
our data show that there are very few relevant media texts online within the
timeframe of this study, and the majority of them appear after the first page of
Google News SERP. But, most texts present a negative tone or connotation, and a
lot of links to online and social media embedded in these texts extend their
traffic and reach.
PMID- 29951202
TI - Self-reported mobility as a preoperative risk assessment tool in older surgical
patients compared to the American College of Surgeons National Surgical Quality
Improvement Program.
AB - Background: The American College of Surgeons National Surgical Quality
Improvement Program (NSQIP(r)) developed a surgical risk calculator using data
from 1.4 million patients and including 1557 unique Current Procedural
Terminology (CPT) codes. Although this calculator demonstrated excellent
performance in predicting postoperative mortality, morbidity, and six surgical
complications, it was not developed specifically for use in older surgical
patients who have worse surgical outcomes and additional unique risk factors
compared to younger adults. We aimed to test the ability of a simple self
reported mobility tool to predict postoperative outcomes in the older surgical
population compared to the NSQIP. Methods: We used data from a prospective cohort
study that enrolled 197 older surgical patients (>= 69 years) undergoing various
elective surgeries and assessed 30-day surgical outcomes. Statistical models
included data from the Mobility Assessment Tool-short form (MAT-sf) alone,
covariates alone, and MAT-sf data and covariates. We used leave-one-out (LOO)
cross-validation of the models within our cohort and compared their performance
for predicting postoperative outcomes against the NSQIP calculator based on
receiver operating characteristic area under the curve (ROC AUC). Results:
Patients with poor self-reported mobility experienced higher rates of
postoperative complications and nursing home placement. There was no difference
in performance between any of our models and the NSQIP calculator (p > 0.1), with
AUC between 0.604 and 0.697 for predicting postoperative complications and 0.653
and 0.760 for predicting nursing home placement. All models also predicted a
length of stay (LOS) similar to the actual LOS. Conclusion: Mobility assessment
alone using MAT-sf can predict postoperative complications, nursing home
placement, and LOS for older surgical patients, with accuracy comparable to that
of the NSQIP calculator. The simplicity of this noninvasive risk assessment tool
makes it an attractive alternative to the NSQIP calculator that requires 20
patient predictors and the planned procedure, or CPT code to predict the chance
that patients will have 15 different adverse outcomes following surgery.
PMID- 29951203
TI - Anesthesiologists as perioperative hospitalists and outcomes in patients
undergoing major urologic surgery: a historical prospective, comparative
effectiveness study.
AB - Background: Perioperative care has been identified as an area of wide variability
in quality, with conflicting models, and involving multiple specialties. In 2014,
the Loma Linda University Departments of Anesthesiology and Urology implemented a
perioperative hospitalist service (PHS), consisting of anesthesiology-trained
physicians, to co-manage patients for the entirety of their perioperative period.
We hypothesized that implementation of this PHS model would result in an
improvement in patient recovery. Methods: As a quality improvement (QI)
initiative, the PHS service was formed of selected anesthesiologists who received
training on the core competencies for hospitalist medicine. The service was
implemented following a co-management agreement to medically manage patients
undergoing major urologic procedures (prostatectomy, cystectomy, and
nephrectomy). Impact was assessed by comparisons to data from the year prior to
PHS service implementation. Data was compared with and without propensity
matching. Primary outcome marker was a reduction in length of stay. Secondary
outcome markers included complication rate, return of bowel function, number of
consultations, reduction in total direct patient costs, and bed days saved.
Results: Significant reductions in length of stay (p < 0.05) were demonstrated
for all surgical procedures with propensity matching and were demonstrated for
cystectomy and nephrectomy cases without. Significant reductions in complication
rates and ileus were also observed for all surgical procedures post-PHS
implementation. Additionally, reductions in total direct patient costs and
frequency of consultations were also observed. Conclusions: Anesthesiologists can
safely function as perioperative hospitalists, providing appropriate medical
management, and significantly improving both patient recovery and throughput.
PMID- 29951204
TI - Web Tool for Navigating and Plotting SomaLogic ADAT Files.
AB - SOMAscanTM is a complex proteomic platform created by SomaLogic. Experimental
data resulting from the assay is provided by SomaLogic in a proprietary text
based format called ADAT. This manuscript describes a user-friendly point and
click open source, platform-independent software tool designed to be used for
navigating and plotting data from an ADAT file. This tool was used either alone
or in conjunction with other tools as a first pass analysis of the data on
several different on-going research projects. We have seen a need from our
experience for a web interface to the ADAT file so that users can navigate,
generate plots, perform QC and conduct statistical analysis on their own data in
a point and click manner. After several rounds of interacting with biologists and
their requirements with respect to data analysis, we present an online
interactive Shiny Web Tool for Navigating and Plotting data contained within the
ADAT file. Extensive video tutorials, example data, the tool and the source code
are available online.
PMID- 29951205
TI - Effects of breast structure on high-intensity focused ultrasound focal error.
AB - Background: The development of imaging technologies and breast cancer screening
allowed early detection of breast cancers. High-intensity focused ultrasound
(HIFU) is a non-invasive cancer treatment, but the success of HIFU ablation was
depending on the system type, imaging technique, ablation protocol, and patient
selection. Therefore, we aimed to determine the relationship between breast
tissue structure and focal error during breast cancer HIFU treatment. Methods:
Numerical simulations of the breast cancer HIFU ablation were performed using
digital breast phantoms constructed using the magnetic resonance imaging data
obtained from 12 patients. Results: The focal shapes were distorted despite
breast tissue representing soft tissue. Focal errors are caused by the complex
distribution of fibroglandular tissue, and they depend on the target position and
the arrangement of the transducer. We demonstrated that the focusing ratio
increases with the decrease in the local acoustic inhomogeneity, implying that it
may be used as an indicator to reduce the HIFU focal error depending on the
breast structure. Conclusions: The obtained results demonstrated that the focal
error observed during the breast cancer HIFU treatment is highly dependent on the
structure of fibroglandular tissue. The optimal arrangement of the transducer to
the target can be obtained by minimizing the local acoustic inhomogeneity before
the breast cancer HIFU treatment.
PMID- 29951206
TI - Activity seascapes highlight central place foraging strategies in marine
predators that never stop swimming.
AB - Background: Central place foragers (CPF) rest within a central place, and theory
predicts that distance of patches from this central place sets the outer limits
of the foraging arena. Many marine ectothermic predators behave like CPF animals,
but never stop swimming, suggesting that predators will incur 'travelling' costs
while resting. Currently, it is unknown how these CPF predators behave or how
modulation of behavior contributes to daily energy budgets. We combine acoustic
telemetry, multi-sensor loggers, and hidden Markov models (HMMs) to generate
'activity seascapes', which combine space use with patterns of activity, for reef
sharks (blacktip reef and grey reef sharks) at an unfished Pacific atoll.
Results: Sharks of both species occupied a central place during the day within
deeper, cooler water where they were less active, and became more active over a
larger area at night in shallower water. However, video cameras on two grey reef
sharks revealed foraging attempts/success occurring throughout the day, and that
multiple sharks were refuging in common areas. A simple bioenergetics model for
grey reef sharks predicted that diel changes in energy expenditure are primarily
driven by changes in swim speed and not body temperature. Conclusions: We provide
a new method for simultaneously visualizing diel space use and behavior in marine
predators, which does not require the simultaneous measure of both from each
animal. We show that blacktip and grey reef sharks behave as CPFs, with diel
changes in activity, horizontal and vertical space use. However, aspects of their
foraging behavior may differ from other predictions of traditional CPF models. In
particular, for species that never stop swimming, patch foraging times may be
unrelated to patch travel distance.
PMID- 29951207
TI - Potential role for histone deacetylation in chronic diazepam-induced
downregulation of alpha1-GABAA receptor subunit expression.
AB - Corroborating evidence indicate that the downregulation of GABAA receptor subunit
expression may underlie tolerance to the anticonvulsant and anxiolytic actions of
benzodiazepine (BZ) ligands that act as full allosteric modulators (FAMs) of GABA
actions at a variety of GABAA receptor subtypes. We and others have shown that 10
14 days treatment with increasing doses of diazepam (a FAM) resulted in
anticonvulsant tolerance and decreased the expression of the alpha1 GABAA
receptor subunit mRNA and protein in frontal cortex. In addition, we have also
shown that long-term treatment with imidazenil, a partial allosteric modulator of
GABA action at selective GABAA receptor subtypes, fail to change the expression
of the alpha1 subunit mRNA or induce tolerance to its anticonvulsant or
anxiolytic action. However, little is known regarding the potential role of
epigenetic mechanisms on long-term BZ-induced downregulation of GABAA receptor
subunit. Therefore, we examined the role of histone acetylation and DNA
methylation mechanisms on long-term diazepam-induced downregulation of the alpha1
subunit mRNA expression in rat frontal cortex. We found that 10 days treatment
with increasing doses of diazepam but not imidazenil decreased the expression of
the alpha1 GABAA receptor subunit mRNA and promoter acetylation in frontal
cortex. In addition, we also found that 10 days treatment with diazepam but not
imidazenil increased the expression of histone deacetylase (HDAC) 1 and 2 in
frontal cortex. Thus, the increased expression of HDAC1 and HDAC2 (class 1 HDACs)
and consequently increased histone deacetylation mechanism of this class 1 HDACs,
may underlie long-term diazepam-induced decreased expression of the alpha1 GABAA
receptor subunit mRNA in frontal cortex.
PMID- 29951208
TI - Regulatory requirements for the registration of generic medicines and format of
drug dossiers: procedures in Sri Lanka in comparison with selected regulatory
authorities.
AB - Background: The regulatory requirements for approval of generic medicines and the
format of compiling drug dossiers vary among regulatory authorities. The
variation is particularly wide between High-income countries (HIC) and lower and
middle-income countries (LMIC) with different regulatory frameworks. In this
study, document requirements for approval of generic products, approval
timelines, and consideration of bioequivalence and/or biowaiver data by
Regulatory Authorities (RAs) of 10 selected jurisdictions was studied. Methods:
The guidelines and procedures from 5 purposively chosen RA of HIC and4 regional
RAs relevant for Sri Lanka were compared with the Sri Lankan National Medicines
Regulatory Authority (NMRA). Information available in the official websites of
the selected RAs, published journal articles and via personal communication was
collected in2016. Drug approval timelines achieved in Sri Lanka was obtained from
data available from another study. Results: Common technical dossier (CTD) format
of the International Council on Harmonization (ICH) for registration of
pharmaceuticals (ICH:CTD) or the Association of South East Asian Nations (ASEAN)
CTD format (ACTD) was used by all RAs studied except Sri Lanka which use its own
dossier format. Nine out of ten RAs studied request BE data or justification for
not submitting BE data for generic medicines. Sri Lanka requested BE studies only
for antimicrobials, antiepileptic drugs and narrow therapeutic index drugs.
Biowaivers are allowed for Biopharmaceutics Classification System (BCS)-based
Class 1drugs in Singapore and India. USA, EMA, Canada and South Korea allowed
biowaiver for BCS Class1and Class 3drugs but Sri Lanka does not accept BW at
present. Nine NMRAs out of the ten studied reported legislated timelines for
approval of generic pharmaceuticals except Sri Lanka. Conclusions: Streamlining
the drug regulatory systems in LMIC such as Sri Lanka with that of HIC would
facilitate an effective drug regulatory system based on reliance on decisions
made by stringent regulatory authorities. Findings of this study encourage Sri
Lanka to adopt a CTD format for regulatory submission of drug dossiers. Expanding
the BE requirement drug list and accepting BCS-based biowaivers for BSC class 1
and 3 drugs during registration of generic drugs when it is scientifically
justified is also recommended for Sri Lanka.
PMID- 29951210
TI - Land-use patterns and their implication on malaria transmission in Kilosa
District, Tanzania.
AB - Background: Understanding of the land use and malaria transmission among farming
communities in Tanzania is of great significance. Water resource development
projects, deforestation, wetland cultivation, and land use changes for
agricultural purposes all expand habitats for malaria-carrying mosquitoes. The
main objective of this study was to assess land use patterns and their
implication on malaria transmission in two villages in Kilosa District, Tanzania.
Methods: Multiple research methods were used for data collection, including
household interviews using a structured questionnaire; key informant interviews;
transect walks and direct field observations. A larval search was conducted using
the dipper standard method whereby mosquito larvae and pupae were identified to
genus level. Data analysis was undertaken using the Stata software version 10 and
descriptive statistics were used. Results: A total of 211 diverse mosquito
breeding habitats were surveyed during this study. The mosquito breeding sites
ranged from small areas such as hoof prints and coconut shells to large ones such
as swamps created through anthropogenic activities. The relationships between
land use patterns and malaria transmission were statistically insignificant,
indicating that malaria transmission in Kilosa could possibly be due to other
human activities, including seasonal movement to distant farms during farming
seasons. Communities were knowledgeable about malaria preventive measures such as
the use of mosquito nets. While knowledge that links mosquitoes and malaria was
relatively high among respondents, knowledge related to mosquito ecology and
breeding sites was generally low. Conclusion: Although analysis of land use
patterns did not show statistical significance in the study area, agricultural
activities, brick making and settlement seem to be highly linked to malaria
transmission. The association of land use patterns and malaria transmission is
well observed in habitats created that harbour mosquitoes, and evidenced by
presence of immature Anopheles mosquito larvae. Lack of knowledge of the
epidemiology of transmission by the inhabitants is a major issue. Although it
might be difficult to change land use patterns, as they are driven by economic
necessity, future reduction of spread, through better education, is something
that could be modified. In addition, more detailed studies are recommended to
further confirm the linkages between land use/cover changes and malaria
transmission in the study area.
PMID- 29951209
TI - Air displacement plethysmography (pea pod) in full-term and pre-term infants: a
comprehensive review of accuracy, reproducibility, and practical challenges.
AB - Air displacement plethysmography (ADP) has been widely utilised to track body
composition because it is considered to be practical, reliable, and valid. Pea
Pod is the infant version of ADP that accommodates infants up to the age of 6
months and has been widely utilised to assess the body composition of full-term
infants, and more recently pre-term infants. The primary goal of this
comprehensive review is to 1) discuss the accuracy/reproducibility of Pea Pod in
both full- and pre-term infants, 2) highlight and discuss practical challenges
and potential sources of measurement errors in relation to Pea Pod operating
principles, and 3) make suggestions for future research direction to overcome the
identified limitations.
PMID- 29951211
TI - Cardiometabolic risk factors in treatment-seeking youth versus population youth
with obesity.
AB - Background: Although obesity affects approximately one in five youths, only a
fraction is treated in pediatric weight management clinics. Characteristics
distinguishing youth with obesity who seek weight management treatment from those
who do not are largely unknown. Yet identification of specific health
characteristics which differentiate treatment-seeking from non-treatment seeking
youth with obesity may shed light on underlying motivations for pursuing
treatment. Objectives: Compare the cardiometabolic profiles of an obesity
treatment-seeking sample of youth to a population-based sample of youth with
obesity, while controlling for body mass index (BMI). Methods: This cross
sectional study included participants, ages 12-17 years, with obesity from the
Pediatric Obesity and Weight Evaluation Registry (POWER) and National Health and
Nutrition Examination Survey, representing the treatment-seeking and population
samples, respectively. Mean differences were calculated for systolic and
diastolic blood pressure percentiles, total cholesterol, low-density and high
density lipoprotein-cholesterol, triglycerides, fasting glucose, glycated
hemoglobin and alanine aminotransferase, while adjusting for age, sex,
race/ethnicity, insurance status, and multiple of the 95th BMI percentile.
Results: The POWER and National Health and Nutrition Examination Survey cohorts
included 1,823 and 617 participants, respectively. The POWER cohort had higher
systolic blood pressure percentile (mean difference 17.4, 95% confidence interval
[14.6, 20.1], p < 0.001), diastolic blood pressure percentile (21.8 [19, 24.5], p
< 0.001), triglycerides (42.3 [28, 56.5], p < 0.001) and alanine aminotransferase
(7.5 [5.1, 9.8], p < 0.001) and lower fasting glucose (-6.9 [-8.2, -5.6], p <
0.001) and high-density lipoprotein-cholesterol (-2.3 [-3.8, -0.9], p < 0.002).
There were no differences in total cholesterol or low-density lipoprotein
cholesterol or clinical differences in glycated hemoglobin. Conclusion: For a
given BMI, obesity treatment-seeking youth are more adversely affected by
cardiometabolic risk factors than the general population of youth with obesity.
This suggests that treatment-seeking youth may represent a distinct group that is
at particularly high risk for the development of future cardiometabolic disease.
PMID- 29951212
TI - Obesity, underweight and BMI distribution characteristics of children by gross
national income and income inequality: results from an international survey.
AB - BACKGROUND: Economic wealth and income inequality may impact on childhood BMI
distribution by affecting overconsumption of food and sedentary forms of
transportation and entertainment across the whole or some of the population.
OBJECTIVES: To determine whether BMI distribution of children differs by gross
national income (GNI) per capita and Gini index derived from World Bank data.
METHODS: Secondary analysis of largely self-reported height and weight data from
a multi-country, cross-sectional study (ISAAC), of 77,963 children aged 6-7 (from
19 countries) and 205,388 adolescents aged 13-14 (from 36 countries), were used
to examine underweight vs obesity prevalence and BMI distribution skewness,
median and dispersion. RESULTS: Children and adolescents from 'lower' GNI
countries had higher prevalence of underweight than those from 'higher' GNI
countries (6% vs 3%, p = 0.03; 2% vs 1%, p = 0.05 respectively), but the
prevalence of obesity was not different (2% vs 5%, p = 0.29; 2% vs 2%, p = 0.66).
BMI distribution of participants from 'higher' GNI countries had higher median,
without significant difference in skewness or dispersion compared to 'lower' GNI
countries (higher medians +1.1 kg/m2 for 6-7 year olds, and + 0.7 kg/m2, +1.2
kg/m2 for 13-14 year old girls and boys respectively). Gini index was not
associated with underweight or obesity prevalence in either children or
adolescents, nor with any BMI distribution characteristics with one exception.
Adolescent girls from higher income inequality countries had a greater median BMI
(+0.7 kg/m2) and a less skewed BMI distribution. CONCLUSIONS: It appears that the
obesogenic impact of economic prosperity affects all children similarly. Income
inequality may have a gender specific effect affecting BMI distribution in
adolescent girls.
PMID- 29951213
TI - Inequality in physical activity, sedentary behaviour, sleep duration and risk of
obesity in children: a 12-country study.
AB - Objective: Studies examining associations between movement behaviours (i.e.
physical activity, sedentary behaviour and sleep duration) and obesity focus on
average values of these movement behaviours, despite important within-country and
between-country variability. A better understanding of movement behaviour
inequalities is important for developing public health policies and behaviour
change interventions. The objective of this ecologic analysis at the country
level was to determine if inequality in movement behaviours is a better correlate
of obesity than average movement behaviour volume in children from all inhabited
continents of the world. Methods: This multinational, cross-sectional study
included 6,128 children 9-11 years of age. Moderate-to-vigorous physical activity
(MVPA), total sedentary time (SED) and sleep period time were monitored over 7
consecutive days using waist-worn accelerometry. Screen time was self-reported.
Inequality in movement behaviours was determined using Gini coefficients (ranging
from 0 [complete equality] to 1 [complete inequality]). Results: The largest
inequality in movement behaviours was observed for screen time (Gini of 0.32;
medium inequality), followed by MVPA (Gini of 0.21; low inequality), SED (Gini of
0.07; low inequality) and sleep period time (Gini of 0.05; low inequality).
Average MVPA (h d-1) was a better correlate of obesity than MVPA inequality (r =
0.77 vs. r = 0.00, p = 0.03). Average SED (h d-1) was also a better correlate of
obesity than SED inequality (r = 0.52 vs. r = -0.32, p = 0.05). Differences in
associations for screen time and sleep period time were not statistically
significant. MVPA in girls was found to be disproportionally lower in countries
with more MVPA inequality. Conclusions: Findings from this study show that
average MVPA and SED should continue to be used in population health studies of
children as they are better correlates of obesity than inequality in these
behaviours. Moreover, the findings suggest that MVPA inequality could be greatly
reduced through increases in girls' MVPA alone.
PMID- 29951214
TI - A narrative review of the construct of hedonic hunger and its measurement by the
Power of Food Scale.
AB - Introduction: The term 'hedonic hunger' refers to one's preoccupation with and
desire to consume foods for the purposes of pleasure and in the absence of
physical hunger. The Power of Food Scale (PFS) was developed as a quantitative
measure of this construct in 2009. Since then, over 50 published studies have
used the PFS to predict appetite-related outcomes including neural, cognitive,
behavioural, anthropometric and clinical measures. Objective: This narrative
review evaluates how closely the PFS captures the construct it was originally
presumed to assess and to more clearly define hedonic hunger itself. Methods: The
measure's relationship to four domains is reviewed and summarized: motivation to
consume palatable foods; level of actual consumption of such foods; body mass;
and subjective loss-of-control over one's eating behaviour. Findings are
synthesized to generate a more accurate understanding of what the PFS measures
and how it may relate to the broader definition of hedonic hunger. Results:
Results suggest that the PFS is closely related to motivation to consume
palatable foods and, in extreme cases, occurrence of loss-of-control eating
episodes. PFS scores are not consistently predictive of amount of food consumed
or body mass. Conclusions: Implications of these findings are discussed in the
context of behavioural health, and avenues for further inquiry are identified.
PMID- 29951215
TI - Preferences for physician weight status among women with overweight.
AB - Background: Women with overweight experience stigma in clinical interactions.
Emerging evidence suggests that one near-term approach to offset the negative
consequences of weight stigma could be to capitalize on benefits of patient
physician weight concordance. However, it is likely that patient attitudes
towards physicians with overweight are complicated and multifaceted and may
include stigmatization of providers with overweight. Methods: Two-hundred ninety
eight women with overweight completed an online questionnaire and indicated
preference for a physician who is 'overweight', 'not overweight', or indicated no
preference. Participants provided reasons for their choice and answered questions
about their weight-related beliefs and experiences. Results: The majority of
women indicated no weight preference (63%), and a portion (36%) of the sample
explicitly preferred physicians who are not overweight. Reasons provided for
these preferences were primarily based on stereotyped notions of physician
aptitude based on weight. Compared with having no preference, those who preferred
physicians who are not overweight had fewer previous negative weight-related
physician interactions and had increased beliefs about the controllability of
weight. Conclusions: These findings elucidate patient attitudes towards
physicians with overweight in a sample at increased risk for weight
stigmatization. Findings underscore the need for stigma-reducing interventions so
that clinical experiences for both women and physicians with overweight can be
improved.
PMID- 29951216
TI - Evaluation of an exercise programme for post-bariatric surgery patients: views of
participants.
AB - Objective: Exercise programmes typically are evaluated with fitness assessments
and psychological survey measures but seldom include participants' insights. The
purpose of this study was to evaluate the benefits, facilitators and barriers of
a 12-week exercise programme for post-bariatric surgery patients from the
participants' perspective. Method: Over a 2-year period, 20 patients recently
having undergone bariatric surgery completed a 12-week programme that included
participation in structured exercise and in focus groups designed to supplement
standard evaluation data and provide insight into participants' views. Results:
Participants were highly adherent to the programme, and focus group results
reflected a clear positive evaluations. Benefits included helpful information,
developing commitment, physical fitness and social support; notably, weight was
seldom mentioned. Participants cited structure, accountability and group support
as facilitators of exercise. Participants cited few barriers, although very few
had set plans for continuing exercise after programme completion. Conclusion:
Participants saw many benefits to the exercise programme, and those benefits
reflected lifestyle changes rather than a focus on weight. Programme structure,
accountability and the support of the group were facilitators to exercise.
Participants cited few barriers. However, the lack of plans for continued
exercise suggested the need for a transition phase to help participants continue
an active lifestyle after the 12-week structured programme.
PMID- 29951217
TI - Racial differences in intracerebral haemorrhage outcomes in patients with
obesity.
AB - Objective: This study was conducted to determine the role of obesity and race in
intracerebral haemorrhage (ICH) outcomes. Methods: The Get with the guideline
Stroke database was queried for all admitted patients with spontaneous ICH.
Secondary causes of ICH were excluded. Body mass index (BMI) was classified using
the Center for Disease Control guidelines. Race was classified as White or non
White. Demographics, clinical, imaging data were retrieved. Outcome measures were
hematoma expansion at 24 h and discharge disposition. Results: A total of 428
patients were included in our analysis. Female gender, past history of congestive
heart failure, diabetes mellitus, HbA1c, blood pressure, ICH volume, ICH
location, intraventricular haemorrhage and hospital length of stay deferred
across BMI categories. On multivariate analysis, along with obese categories,
age, ICH location and ICH volume were independent predictors of poor outcomes
(hematoma expansion and poor discharge disposition). After adjusting for these
variables, obesity remained a predictor of poor disposition outcome compared with
normal and overweight subjects; Normal vs. Obese OR 0.26 CI 0.115-0.593 p =
0.0014; Obese vs. Overweight OR 3.79 CI 1.68-8.52 p = 0.0013. Nonetheless,
obesity did not influence hematoma expansion. Overall, BMI-race classification
did not influence outcomes. However, among non-Whites, the obese category had
higher odds of a poor disposition outcome than normal (OR 6.84 CI 2.12-22.22 p =
0.0013) or overweight (OR 8.45 CI 2.6-27.49 p = 0.0004) categories. Conclusion:
An obesity paradox in ICH was not observed in our cohort. In the non-White
population, patients with obesity were likely to be associated with poor
disposition outcome. Similar findings were not observed in White population.
PMID- 29951218
TI - Validation of the Stanford Leisure-Time Activity Categorical Item (L-Cat) using
armband activity monitor data.
AB - Objective: Accurate assessment of physical activity (PA) in public health and
healthcare settings remains a challenge given limitations of existing brief
assessment tools. The Stanford Leisure-Time Activity Categorical Item (L-Cat), a
single item with six categories, has previously demonstrated excellent
reliability and adequate validity relative to pedometer steps. However,
pedometers cannot assess key dimensions of PA intensity or duration. Methods: We
evaluated the L-Cat's criterion validity and sensitivity to change relative to
objectively measured Sensewear armband activity monitors among 76 adults with
overweight/obesity (mean age 50.8 +/- 11.9 years, BMI = 33.1 +/- 3.4 kg m-2) at
baseline and end of a 6-month behavioural weight management pilot trial. Results:
At baseline, L-Cat category was associated with armband-measured daily steps
(Spearman's rho = 0.41, p < 0.001), total weekly minutes of moderate/vigorous
intensity PA (MVPA) (rho = 0.40, p < 0.001) and weekly minutes of MVPA
accumulated in bouts >=10 min (rho = 0.47, p < 0.0001). Participants increasing
>=1 L-Cat category from baseline to 6 months had greater increases in steps
(1,110.1 +/- 1,852.1 vs. -18.0 +/- 2,005.6 steps/d, p = 0.032), total minutes of
MVPA (145.7 +/- 180.6 vs. -2.1 +/- 215.8 min/week, p = 0.007) and greater weight
losses (-7.4 +/- 7.7% vs. -3.1 +/- 4.8%, p = 0.013) than those who stayed the
same/decreased L-Cat categories. Conclusion: The L-Cat demonstrated adequate
criterion validity and excellent sensitivity to change relative to objectively
measured PA among behavioural weight management pilot trial participants. The L
Cat may be particularly useful for identifying individuals at lower activity
levels and when using all six categories.
PMID- 29951219
TI - Self-monitoring has no adverse effect on disordered eating in adults seeking
treatment for obesity.
AB - Objectives: Although monitoring is considered a key component of effective
behaviour change, the development of apps has allowed consumers to constantly
evaluate their own diet, with little examination of what this might mean for
eating behaviour. The aim of this study was to investigate whether self
monitoring of diet using the app MyFitnessPal or daily self-weighing increases
the reported occurrence of eating disorders in adults with overweight/obesity
following a weight loss programme. Methods: Two hundred fifty adults with body
mass index >= 27 kg/m2 received diet and exercise advice and were randomized to
one of four monitoring strategies (daily self-weighing, MyFitnessPal, brief
monthly consults or self-monitoring hunger) or control for 12 months. The Eating
Disorder Examination Questionnaire 6.0 was used to assess eating disorder
symptoms and behaviours for the previous 28 d at 0 and 12 months. Results: There
were no significant differences in the global Eating Disorder Examination
Questionnaire score or the subscales between those in the four monitoring groups
and the control at 12 months (all p >= 0.164), nor were there differences in
binge eating, self-induced vomiting, laxative misuse or excessive exercise at 12
months (p >= 0.202). The overall prevalence of one or more episodes of binge
eating was 53.6% at baseline and 50.6% at 12 months, with no change over time (p
= 0.662). Conclusions: There was no evidence that self-monitoring, including
using diet apps like MyFitnessPal or daily self-weighing, increases the reported
occurrence of eating disorder behaviours in adults with overweight/obesity who
are trying to lose weight.
PMID- 29951220
TI - Men who were thin during early adulthood exhibited greater weight gain-associated
visceral fat accumulation in a study of middle-aged Japanese men.
AB - Objective: This study aimed to assess the relationship between weight gain from
early adulthood and visceral fat accumulation. Methods: The participants were 549
men aged 42 to 64 years who were randomly selected from the local resident
registry for the National Institute for Longevity Sciences' neighbourhood. They
were asked to recall their weight at 18 years of age, and then, post-18 weight
change values were calculated for each participant (their current weight minus
their weight at 18). The participants were divided according to their median body
mass index (BMI) at 18 years of age (initial BMI) (<20.14 and >=20.14 kg m-2).
Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured on computed
tomography scans. Results: The participants with initial BMI of <20.14 kg m-2
exhibited greater post-18 weight changes than those with initial BMI of >=20.14
kg m-2. The participants' post-18 weight-change values were negatively correlated
with their initial BMI and positively correlated with both VFA and SFA. The slope
of the regression line for the relationship between post-18 weight change and VFA
was steeper in the participants with initial BMI of <20.14 kg m-2 (beta = 4.36)
than in those with initial BMI of >=20.14 kg m-2 (beta = 3.23). Conclusions:
Visceral fat accumulation is affected not only by an individual's post-18 weight
gain but also by their initial BMI. Men who were thin in early adulthood
experienced greater weight gain-associated VFA increases, but the same was not
true for SFA.
PMID- 29951222
TI - Determinants of unmet need for family planning among married women of
reproductive age in Burundi: a cross-sectional study.
AB - Background: High unmet need for family planning (32.4%) characterized Burundi in
2010. However, there has not been any study examining the relationship between
unmet need and associated factors in Burundi. The present study aims at
determining the demographic, socioeconomic and other factors underlying the unmet
need for contraception among married women aged 15-49 in Burundi. Methods: This
study used data from the 2010 Burundi Demographic and Health Survey. Total unmet
need, unmet need for spacing and for limiting were used as outcomes and
demographic, socioeconomic and other factors as independent variables. After a
descriptive analysis of the study population (n = 5421), the association between
the three outcomes and the independent variables were analysed using logistic
regression. Odds ratios with their 95% confidence intervals were calculated with
statistical significance at p < 0.05. Results: This study showed that the
likelihood of total unmet need decreased with age after 35+, with an adjusted
Odds Ratio = 0.586 and 95% CI = 0.423-0.811, compared to women aged 15-24. Women
with 4-5 and 6+ living children had higher odds [aOR = 1.850 (1.322-2.590) and
2.390 (1.616-3.534) respectively]. Odds of unmet need were lower among women with
primary [aOR = 0.741 (0.618-0.888)] and secondary education [aOR = 0.555 (0.399
0.771)]. Women whose husband desired more children than them [aOR = 1.824 (1.411
2.358)] and those ignoring the husband's desired children [aOR = 2.700 (2.176
3.350)] had higher odds than those desiring the same number as the husband. Women
who had experienced the death of 1+ sons had higher odds [aOR = 1.285 (1.038
1.591)]. Middle [aOR = 0.670 (0.530-0.846)] and rich [aOR = 0.664 (0.541-0.817)]
compared to poor, women living in the North [aOR = 0.611 (0.412-0.904)] compared
to those from Bujumbura, had lower odds. Rural women had higher odds [aOR = 1.373
(1.018-1.852)] and those who had visited a health facility [aOR = 0.765 (0.608
0.961)] or had access to TV [aOR = 0.562 (0.375-0.843)] had lower odds.
Conclusion: Tackling the unmet need for FP in Burundi requires scaling-up male
involvement, promoting spousal communication, client-centred services, greater
use of media, women's education, child survival, and pro-poor policies.
PMID- 29951221
TI - GeriMedRisk, a telemedicine geriatric pharmacology consultation service to
address adverse drug events in long-term care: a stepped-wedge cluster randomized
feasibility trial protocol (ISRCTN17219647).
AB - Background: Multimorbidity, polypharmacy, and older age predispose seniors to
adverse drug events (ADE). Seniors with an ADE experience greater morbidity,
mortality, and health care utilization compared to their younger counterparts. To
mitigate and manage ADEs among this vulnerable population, we designed a
geriatric pharmacology consultation service connecting clinicians with specialist
physicians and pharmacists and will investigate the feasibility and acceptability
of this complex intervention in the long-term care setting, prior to conducting a
larger efficacy trial. Methods/Design: We will conduct a cluster randomized
feasibility trial and qualitative analysis of GeriMedRisk among four long-term
care homes in the Waterloo-Wellington region from May 1 to December 31, 2017. The
primary outcome is the feasibility and acceptability of GeriMedRisk and the
stepped-wedge cluster randomized controlled trial design. We hypothesize that
GeriMedRisk is a feasible intervention and its potential to decrease falls and
drug-related hospital visits can be evaluated with a stepped-wedge cluster
randomized controlled trial design. Discussion: This mixed methods study will
inform a larger efficacy trial of GeriMedRisk's ability to decrease adverse drug
events among seniors in the long-term care setting. Ethics and dissemination: The
Hamilton Integrated Research Ethics Board granted the approval for this study
protocol 2812. We plan to disseminate the results of this study in peer-reviewed
journals and also to our partners and stakeholders. Trial registration: ISRCTN
clinical trials registry, ISRCTN17219647 (March 27, 2017).
PMID- 29951223
TI - The annual rate of coronary artery calcification with combination therapy with a
PCSK9 inhibitor and a statin is lower than that with statin monotherapy.
AB - Statins and/or PCSK9 inhibitors cause the regression of coronary atheroma and
reduce clinical events. However, it currently remains unclear whether these drugs
modulate coronary atheroma calcification in vivo. Coronary artery calcium (CAC)
scores (Agatston Units, AUs) were estimated in 120 patients receiving coronary
computed tomographic angiography (CCTA) (63% males; median age 56 years). The CAC
scores were compared among the three groups: (1) neither statin nor PCSK9
inhibitor therapy, (2) statin monotherapy, and (3) statin and PCSK9 inhibitor
combination therapy in an unpaired cross-sectional study. Additionally, CCTA was
performed twice at an interval in 15 patients undergoing statin monotherapy to
compare the previous (baseline) and subsequent (follow-up) CAC scores in a paired
longitudinal study. In addition, a PCSK9 inhibitor was administered to 16
patients undergoing statin therapy. Before and after that, CCTA was performed
twice to compare the previous and subsequent CAC scores in a paired longitudinal
study. The unpaired cross-sectional study and paired longitudinal study consist
of completely different patients. Among 120 patients, 40 (33%) had a CAC score
>100 AUs. The median CAC score increased in the following order: statin group,
statin and PCSK9 group, and no-statin-no-PCSK9 group. Annual CAC score
progression was 29.7% by statin monotherapy and 14.3% following the addition of
the PCSK9 inhibitor to statin therapy. The annual rate of CAC with the
combination therapy with a PCSK9 inhibitor and a statin is lower than that with
statin monotherapy. CAC may be prevented with PCSK9 Inhibitor.
PMID- 29951225
TI - Signaling pathway screening platforms are an efficient approach to identify
therapeutic targets in cancers that lack known driver mutations: a case report
for a cancer of unknown primary origin.
AB - Precision medicine aims to tailor cancer therapies to target specific tumor
promoting aberrations. For tumors that lack actionable drivers, which occurs
frequently in the clinic, extensive molecular characterization and pre-clinical
drug efficacy studies will be required. A cell line maintained at low passage and
a patient- derived xenograft model (PDX) were generated using a fresh biopsy from
a patient with a poorly-differentiated neuroendocrine tumor of unknown primary
origin. Next-generation sequencing, high throughput signaling network analysis,
and drug efficacy trials were then conducted to identify actionable targets for
therapeutic intervention. No actionable mutations were identified after whole
exome sequencing of the patient's DNA. However, whole genome sequencing revealed
amplification of the 3q and 5p chromosomal arms, that include the PIK3CA and
RICTOR genes, respectively. We then conducted pathway analysis, which revealed
activation of the AKT pathway. Based on this analysis, efficacy of PIK3CA and AKT
inhibitors were evaluated in the tumor biopsy-derived cell culture and PDX, and
response to the AKT inhibitor AZD5363 was observed both in vitro and in vivo
indicating the patient would benefit from targeted therapies directed against the
serine/threonine kinase AKT. In conclusion, our study demonstrates that high
throughput signaling pathway analysis will significantly aid in identifying
actionable alterations in rare tumors and guide patient stratification into early
phase clinical trials.
PMID- 29951226
TI - RbFe(HAsO4)2 and TlFe(HAsO4)2, two new hydrogenarsenates adopting two closely
related structure types.
AB - Rubidium iron bis-[hydrogen arsenate(V)], RbFe(HAsO4)2, and thallium iron bis
[hydrogen arsenate(V)], TlFe(HAsO4)2, were grown under mild hydro-thermal
conditions (T = 493 K, 7 d). RbFe(HAsO4)2 adopts the RbFe(HPO4)2 structure type
(space group Rc), while TlFe(HAsO4)2 crystallizes in the (NH4)Fe(HPO4)2 structure
type (space group P ). Both compounds have tetra-hedral-octa-hedral framework
topologies. The M+ cations are located in channels of the respective framework
and are disordered in TlFe(HAsO4)2, which may suggest that the M+ cations can
move in the channels.
PMID- 29951224
TI - Sea cucumber genome provides insights into saponin biosynthesis and aestivation
regulation.
AB - Echinoderms exhibit several fascinating evolutionary innovations that are rarely
seen in the animal kingdom, but how these animals attained such features is not
well understood. Here we report the sequencing and analysis of the genome and
extensive transcriptomes of the sea cucumber Apostichopus japonicus, a species
from a special echinoderm group with extraordinary potential for saponin
synthesis, aestivation and organ regeneration. The sea cucumber does not possess
a reorganized Hox cluster as previously assumed for all echinoderms, and the
spatial expression of Hox7 and Hox11/13b potentially guides the embryo-to-larva
axial transformation. Contrary to the typical production of lanosterol in animal
cholesterol synthesis, the oxidosqualene cyclase of sea cucumber produces parkeol
for saponin synthesis and has "plant-like" motifs suggestive of convergent
evolution. The transcriptional factors Klf2 and Egr1 are identified as key
regulators of aestivation, probably exerting their effects through a clock gene
controlled process. Intestinal hypometabolism during aestivation is driven by the
DNA hypermethylation of various metabolic gene pathways, whereas the
transcriptional network of intestine regeneration involves diverse signaling
pathways, including Wnt, Hippo and FGF. Decoding the sea cucumber genome provides
a new avenue for an in-depth understanding of the extraordinary features of sea
cucumbers and other echinoderms.
PMID- 29951227
TI - Crystal structure of bis-(1-ethyl-1H-imidazole-kappaN3)(5,10,15,20-tetra-phenyl
porphyrinato-kappa4N)iron(II) tetra-hydro-furan monosolvate.
AB - The title complex, [Fe(C44H28N4)(C5H8N2)2].C4H8O, possesses inversion symmetry
with the iron(II) atom located on a center of symmetry. The metal atom is
coordinated in a symmetric octa-hedral geometry by four pyrrole N atoms of the
porphyrin ligand in the equatorial plane and two N atoms of 1-ethyl-imidazole
ligands in the axial sites; the complex crystallizes with a tetra-hydro-furan
solvent mol-ecule. The average Fe-Np (Np is a porphyrin N atom) bond length is
1.995 (3) A and the axial Fe-NIm (NIm is an imidazole N atom) bond length is
1.994 (2) A. The two 1-ethyl-imidazole ligands are mutually parallel. The
dihedral angle between the 1-ethyl-imidazole plane and the plane of the closest
Fe-Np vector is 24.5 degrees . In the crystal, the only significant inter
molecular inter-actions present are C-H?pi inter-actions.
PMID- 29951228
TI - Crystal structure of a new polymorph of (2S,3S)-2-amino-3-methyl-penta-noic acid.
AB - A new polymorph of (2S,3S)-2-amino-3-methyl-penta-noic acid, l-isoleucine
C6H13NO2, crystallizes in the monoclinic space group P21 with four independent
mol-ecules in the asymmetric unit. The mol-ecules are zwitterions. In the
crystal, N-H?O hydrogen bonds link two pairs of independent mol-ecules and their
symmetry-related counterparts to form two types of layers stacked in an anti
parallel manner parallel to (001). The hydro-phobic aliphatic isopropyl groups
protrude from these layers.
PMID- 29951229
TI - Mol-ecular structure, DFT studies and Hirshfeld analysis of anthracenyl chalcone
derivatives.
AB - The mol-ecular and crystal structure of two new chalcone derivatives, (E)-1
(anthracen-9-yl)-3-[4-(piperidin-1-yl)phen-yl]prop-2-en-1-one, C28H25NO, (I), and
(E)-1-(anthracen-9-yl)-3-[4-(di-phenyl-amino)-phen-yl]prop-2-en-1-one, C35H25NO,
(II), with the fused-ring system at the same position are described. In the
crystals of (I) and (II), the mol-ecules are linked via C-H?O hydrogen bonds into
inversion dimers, forming R22(22) and R22(14) ring motifs, respectively. Weak
inter-molecular C-H?pi inter-actions further help to stabilize the crystal
structure, forming a two-dimensional architecture. The mol-ecular structures are
optimized using density functional theory (DFT) at B3LYP/6-311 G++(d,p) level and
compared with the experimental results. The smallest HOMO-LUMO energy gaps of (I)
(exp . 2.76 eV and DFT 3.40 eV) and (II) (exp . 2.70 eV and DFT 3.28 eV)
indicates the suitability of these crystals in optoelectronic applications. All
inter-molecular contacts and weaker contributions involved in the supra-molecular
stabilization are investigated using Hirshfeld surface analysis. The mol-ecular
electrostatic potential (MEP) further identifies the positive, negative and
neutral electrostatic potential regions of the mol-ecules.
PMID- 29951230
TI - Synthesis and structure of an aryl-selenenium(II) cation,
[C34H41N4Se+]2[Hg(SeCN)4]2-, based on a 5-tert-butyl-1,3-bis-(1-pentyl-1H
benzimidazol-2-yl)benzene scaffold.
AB - In the title salt, bis-{[5-tert-butyl-1,3-bis-(1-pentyl-1H-benzimidazol-2
yl)benzene]selenium} tetra-kis-(seleno-cyanato)-mercury,
(C34H41N4Se)2[Hg(SeCN)4], the aryl-selenenium cations, [C34H41N4Se]+, are linked
through [Hg(SeCN)4]2- anions by C-H?N hydrogen bonds. In the cation, the geometry
around the Se atom in the 5-tert-butyl-1,3-bis-(1-pentyl-1H-benzimidazol-2
yl)benzene scaffold is T-shaped, resulting from the coordination of Se by the C
atom of the central aromatic ring and the N atoms of both of the benzimidazole
moieties. The trans Se-N bond lengths are almost equal [2.087 (3) and 2.099 (3)
A] and the Se-C bond length is 1.886 (3) A. The N-Se-N angle is 159.29 (11)
degrees . The geometry around the HgII atom in the [Hg(SeCN)4]2- anion is
distorted tetra-hedral, with Se-Hg-Se angles ranging from 88.78 (3) to 126.64 (2)
degrees . In [Hg(SeCN)4]2-, the Hg-Se bonds are unsymmetrical [2.5972 (4) and
2.7242 (5) A]. One of the pentyl substituents is disordered over two equivalent
conformations, with occupancies of 0.852 (8) and 0.148 (8).
PMID- 29951231
TI - Undeca-carbon-yl[(4-methyl-sulfanylphen-yl)di-phenyl-phosphane]triruthenium(0):
crystal structure and Hirshfeld surface analysis.
AB - The title cluster compound, [Ru3(C19H17PS)(CO)11], comprises a triangle of Ru0
atoms, two of which are bonded to four carbonyl ligands. The third metal atom is
bound to three carbonyl ligands and the phosphane-P atom of a dissymmetric
phosphane ligand, PPh2(C6H4SMe-4); no Ru?S inter-actions are observed. The
phosphane occupies an equatorial position and its proximity to an Ru-Ru edge
results in the elongation of this bond with respect to the others [2.8933 (2) A
cf. 2.8575 (2) and 2.8594 (3) A]. In the crystal, phenyl-C-H?O(carbon-yl) and
carbonyl-O?O(carbon-yl) [2.817 (2) A] inter-actions combine to form a supra
molecular chain propagating along [111]; the chains pack without directional
inter-actions between them. The carbonyl-O?O(carbon-yl) and other weak contacts
have an influence upon the Hirshfeld surfaces with O?H contacts making the
greatest contribution, i.e. 37.4% cf. 15.8% for O?O and 15.6% for H?H contacts.
PMID- 29951232
TI - Crystal structure of 3-hy-droxy-2-(4-hy-droxy-3-meth-oxy-phenyl-methyl)-5,5-di
methyl-cyclo-hex-2-enone.
AB - In the title compound, C16H20O4, a new starting compound for the synthesis of
various heterocycles, the partially saturated six-membered ring adopts a sofa
conformation. An intra-molecular O-H?O hydrogen bond is observed in the guaiacol
residue. In the crystal, mol-ecules are assembled into a sheet structure parallel
to the ab plane via O-H?O hydrogen bonds. The hydrogen-bond pattern is described
by an R44(28) graph-set motif. The sheets are further linked by C-H?O hydrogen
bonds into a three-dimensional network.
PMID- 29951233
TI - Crystal structure of (MU-trans-1,2-bis-{2-[(2-oxido-phen-yl)methyl-idene]hydrazin
1-yl-idene}ethane-1,2-diolato-kappa3O,O',N)bis-[di-tert-butyl-tin(IV)].
AB - The binuclear complex, [Sn2(C4H9)4(C16H10N4O4)], contains two Sn4+ ions,
connected by doubly N-deprotonated oxalylbis[(2-oxido-benzyl-idene)hydrazide]
ligands, and each Sn4+ ion is linked to two tert-butyl groups. The coordination
sphere of each Sn atom is best described as a distorted trigonal bipyramid. Each
stannic ion in the complex is in a C2O2N environment. The two homologous parts of
the doubly deprotonated ligand are located in trans positions with respect to the
C-C bond of the oxalamide group. The oxalamide group exhibits an asymmetric
coordination geometry, as seen by the slight difference between the C-O and C-N
bond lengths. The three-dimensional network is a multilayer of complex mol-ecules
with no strong supramolecular inter-actions.
PMID- 29951234
TI - Crystal structures of two new six-coordinate iron(III) complexes with 1,2
bis(diphenyl-phosphane) ligands.
AB - Structural characterization of the ionic complexes
[FeCl2(C26H22P2)2][FeCl4].0.59CH2Cl2 or [(dppen)2FeCl2][FeCl4].0.59CH2Cl2 (dppen
= cis-1,2-bis-(di-phenyl-phosphane)ethyl-ene, P2C26H22) and
[FeCl2(C30H24P2)2][FeCl4].CH2Cl2 or [(dpbz)2FeCl2][FeCl4].CH2Cl2 (dpbz = 1,2-bis
(di-phenyl-phosphane)benzene, P2C30H24) demonstrates trans coordination of two
bidentate phosphane ligands (bis-phosphanes) to a single iron(III) center,
resulting in six-coordinate cationic complexes that are balanced in charge by
tetra-chlorido-ferrate(III) monoanions. The trans bis-phosphane coordination is
consistent will all previously reported mol-ecular structures of six coordinate
iron(III) complex cations with a (PP)2X2 (X = halido) donor set. The complex with
dppen crystallizes in the centrosymmetric space group C2/c as a partial-occupancy
[0.592 (4)] di-chloro-methane solvate, while the dpbz-ligated complex
crystallizes in the triclinic space group P1 as a full di-chloro-methane
monosolvate. Furthermore, the crystal studied of [(dpbz)2FeCl2][FeCl4].CH2Cl2 was
an inversion twin, whose component mass ratio refined to 0.76 (3):0.24 (3).
Beyond a few very weak C-H?Cl and C-H?pi inter-actions, there are no significant
supra-molecular features in either structure.
PMID- 29951235
TI - Crystal structure of a heterometallic coordination polymer: catena-poly[[[tetra
aqua-cobalt(II)]-MU-pyridine-2,6-di-carboxyl-ato-calcium(II)-MU-pyridine-2,6-di
carboxyl-ato] dihydrate].
AB - In the crystal of the title polymeric complex, {[CoCa(C7H3NO4)2(H2O)4].2H2O} n
(1), the CoII ion is N,O,O'-chelated by two pyridine-2,6-di-carboxyl-ate anions
in a distorted N2O4 octa-hedral geometry, and two carboxyl-ate O atoms of
pyridine-2,6-di-carboxyl-ate anions bridge tetra-aqua-calcium(II) units to form
polymeric chains propagating along the b-axis direction. In the crystal, O-H?O
and C-H?O hydrogen bonds, and offset pi-pi stacking inter-actions [inter-centroid
distances = 3.551 (1) and 3.746 (1) A] involving inversion-related pyridine rings
link the polymeric chains and lattice water mol-ecules to form a supra-molecular
three-dimensional framework.
PMID- 29951236
TI - Crystal structure and Hirshfield surface analysis of 4-phenyl-3-(thio-phen-3
ylmeth-yl)-1H-1,2,4-triazole-5(4H)-thione.
AB - In the title compound, C13H11N3S2, the phenyl ring is twisted from the 1,2,4
triazole plane by 63.35 (9) degrees and by 47.35 (9) degrees from the thio
phene plane. In the crystal, chains of mol-ecules running along the c-axis
direction are formed by N-H?S inter-actions [graph-set motif C(4)]. The 1,2,4
triazole and phenyl rings are involved in pi-pi stacking inter-actions [centroid
centroid distance = 3.4553 (10) A]. The thio-phene ring is involved in C-H?S and
C-H?pi inter-actions. The inter-molecular inter-actions in the crystal packing
were further analysed using Hirshfield surface analysis, which indicates that the
most significant contacts are H?H (35.8%), followed by S?H/H?S (26.7%) and
C?H/H?C (18.2%).
PMID- 29951237
TI - Synthesis and crystal structure of methyl 3-(3-hy-droxy-3-phenyl-prop-2-eno
yl)benzoate.
AB - The title compound, C17H14O4, was synthesized under mild conditions and
characterized by various analytical techniques. Combined NMR and X-ray
diffraction data show that the substance exists exclusively in the enol
tautomeric form. An intra-molecular ?O=C-C=C-OH? hydrogen bond is present in the
mol-ecular structure. The analysis of the difference density map disclosed two
adjacent positions of a disordered hydrogen atom taking part in this hydrogen
bond, indicating the presence of two enol tautomers in the crystal. The enol mol
ecules are assembled through numerous C-H?pi and pi-pi as well as weak C(ar-yl)
H?O inter-actions, thus forming a dense crystal packing. The obtained substance
was also studied by UV-Vis spectroscopy and cyclic voltammetry.
PMID- 29951238
TI - A rare positively charged nicotinic acid di-sulfide: 2,2'-di-thio-dinicotinic
acid hydro-chloride monohydrate.
AB - The title compound {systematic name: 3-carb-oxy-2-[2-(3-carb-oxy-pyridin-2
yl)disulfan-1-yl)]pyridin-1-ium chloride monohydrate}, C12H9N2O4S2+.Cl-.H2O,
crystallizes in the triclinic space group P . A pair of 2-mercaptonicotinic acid
moieties is connected by a 2,2'-di-sulfide bond with a dihedral angle of 78.79
(3) degrees . One of the N atom is protonated, as are both carboxyl-ate groups,
resulting in an overall +1 charge on the dimer. The structure comprises a
zigzagging layer of the dimerized di-thio-dinicotinic acid rings, with charge
balancing chloride ions and water mol-ecules between the layers. Hydrogen bonding
between the chloride and water sites with the dimer appears to hold the structure
together. Nearest neighbor nicotinic acid rings are offset when viewed down the a
axis, suggesting no added stability from ring stacking. The asymmetric unit
corresponds to the empirical formula of the compound, and it packs with two
formula units per unit cell.
PMID- 29951239
TI - Crystal structure of (-)-(R,E)-3-(1,3-benzodioxol-5-yl)-5-[(4S,5R)-5-hy-droxy
methyl-2,2-dimethyl-1,3-dioxolan-4-yl]-N,N-di-methyl-pent-4-enamide.
AB - In the title compound, C20H27NO6, the amide moiety is essentially planar, with a
maximum deviation of 0.073 (3) A, and one of the N-methyl groups shows rotational
disorder. The five-membered 1,3-dioxolane ring adopts an envelope form, with the
C atom bonded to the olefin side chain as the flap, which deviates from the mean
plane through the other four atoms by 0.564 (7) A. The 1,3-dioxole ring fused to
the benzene ring adopts a flattened envelope form, with the C atom between the
two O atoms as the flap, which deviates from the mean plane through the other
four atoms by 0.215 (7) A. The C-C=C-C olefin moiety is essentially planar and
makes a dihedral angle of 87.1 (3) degrees with the benzene ring. An intra
molecular O-H?O hydrogen bond supports the mol-ecular conformation, enclosing an
S(11) graph-set motif. In the crystal, inter-molecular C-H?O hydrogen bonding
links the mol-ecules into a tape running along the b axis. Furthermore, other
weak C-H?O hydrogen bonds and a C-H?pi inter-action connect the tapes into a
sheet structure parallel to (100).
PMID- 29951240
TI - Crystal structures of binary compounds of meldonium 3-(1,1,1-tri-methyl-hydrazin
1-ium-2-yl)prop-ano-ate with sodium bromide and sodium iodide.
AB - 3-(1,1,1-Tri-methyl-hydrazin-1-ium-2-yl)propano-ate (C6H14N2O2, M, more commonly
known under its commercial names Meldonium or Mildronate) co-crystalizes with
sodium bromide and sodium iodide forming polymeric hydrates poly[[tetra-MU-aqua
di-aqua-bis-[3-(1,1,1-tri-methyl-hydrazin-1-ium-2-yl)propano-ate]disodium]
dibromide tetra-hydrate], [Na2(C6H14N2O2)2(H2O)6]Br2.4H2O, and poly[[di-MU-aqua
di-aqua-[MU-3-(1,1,1-tri-methyl-hydrazin-1-ium-2-yl)propano-ate]disodium]
diiodide], [Na2(C6H14N2O2)2(H2O)4]I2. The coordination numbers of the sodium ions
are 6; the coordination polyhedra can be described as distorted octa-hedra. Metal
ions and M zwitterions are assembled into infinite layers via electrostatic inter
actions and hydrogen-bonded networks. These layers are connected via
electrostatic attraction between halogenide ions and positive tri-methyl
hydrazinium groups into a three-dimensional structure.
PMID- 29951241
TI - Synthesis, spectroscopic and Hirshfeld surface analysis and fluorescence studies
of (2E,2'E)-3,3'-(1,4-phenyl-ene)bis-[1-(4-hy-droxy-phen-yl)prop-2-en-1-one] N,N
di-methyl-formamide disolvate.
AB - In the bis-chalcone mol-ecule of the title compound, C24H18O4.2C3H7NO, the
central benzene and terminal hy-droxy-phenyl rings form a dihedral angle of 14.28
(11) degrees and the central C=C double bond adopts a trans configuration. In
the crystal, the bis-chalcone and solvate mol-ecules are inter-connected via O
H?O hydrogen bonds, which were investigated by Hirshfeld surface analysis. Solid
state fluorescence was measured at lambdaex = 4400 A. The emission wavelength
appeared at 5510 A, which corresponds to yellow light and the solid-state
fluorescence quantum yield (Ff) is 0.18.
PMID- 29951242
TI - Crystal structures of 4,4'-(disulfane-1,2-diyl)bis(5-methyl-2H-1,3-dithiol-2-one)
and 4,4'-(diselanane-1,2-diyl)bis(5-methyl-2H-1,3-dithiol-2-one).
AB - The two title compounds, C8H6O2S6 and C8H6O2S4Se2, are isotypic with very similar
cell parameters. The complete mol-ecules constitute the asymmetric units, despite
being chemically perfectly symmetric. The most prominant differences in the
metrical parameters arise from the distinct sizes of sulfur and selenium in the
dichalcogenide bridges, with C-S-S-C and C-Se-Se-C torsion angles of 70.70 (5)
and 68.88 (3) degrees , respectively. The crystal packing is determined by weak
non-classical hydrogen-bonding inter-actions. One carbonyl oxygen but not the
other participates in C-H?O inter-actions zigzagging along the b axis, forming
infinite chains. This is complemented by an intra-molecular C-H?S inter-action
and further inter-molecular C-H?S (C-H?Se) inter-actions, resulting in a three
dimensional network. The inter-actions involving the bridging chalcogenides form
chains protruding along the c axis.
PMID- 29951243
TI - Crystal structures of four new iridium complexes, each containing a highly
flexible carbodi-phos-phorane PCP pincer ligand.
AB - Compound [Ir(C8H12)(C51H45P4)]Cl2 or [Ir(cod)(CH(dppm)2-kappa3P,C,P)]Cl2 (1a),
was obtained from [IrCl(cod)]2 and the carbodi-phospho-rane (CDP) salt
[CH(dppm)2]Cl [where cod = cyclo-octa-1,5-diene and dppm = bis-(di-phenyl
phosphino)methane]. Treatment of 1a with thallium(I) tri-fluoro-methane-sulfonate
[Tl(OTf)] and subsequent crystallization gave complex
[Ir(C8H12)(C51H45P4)](OTf)2.CH3CO2C2H5.CH2Cl2 or [Ir(cod)(CH(dppm)2
kappa3P,C,P)](OTf)2.CH3CO2C2H5.CH2Cl2 (1b) [systematic name: (cyclo-octa-1,5
diene)(1,1,3,3,5,5,7,7-octa-phenyl-1,7-diphospha-3,5-di-phospho-niaheptan-4
yl)iridium(I) bis-(tri-fluoro-methane-sulfonate)-ethyl acetate-di-chloro-methane
(1/1/1)]. This five-coordinate iridium(I) complex cation adopts a trigonal
bipyramidal geometry with the CDP carbon and one cod double bond in axial sites.
Compound 1b represents the first example of a non-meridional coordination of the
PCP pincer ligand [CH(dppm)2]+ with a P-Ir-P angle of 98.08 (2) degrees .
Compound 2, [IrCl2H(C51H44P4)].(CH3)2CO or [IrCl2H(C(dppm)2
kappa3P,C,P)].(CH3)2CO [systematic name: di-chlorido-hydrido(1,1,3,3,5,5,7,7-octa
phenyl-1,5lambda5,7-triphospha-3-phospho-niahept-4-en-4-yl)iridium(III) acetone
monosolvate], crystallizes as an acetone monosolvate. It is a six-coordinate
IrIII coordination compound. Here, the PCP pincer ligand is coordinated in a
meridional manner; one chlorido ligand is positioned trans to the carbon donor,
the remaining two coordination sites being occupied by the second chlorido and a
hydrido ligand trans to each other. Complex 3, [IrCl2H(C51H45P4)]Cl.5H2O or
[IrCl2H(CH(dppm)2-kappa3P,C,P)]Cl.5H2O [systematic name: di-chlorido
hydrido(1,1,3,3,5,5,7,7-octa-phenyl-1,7-diphospha-3,5-di-phospho-niaheptan-4
yl)iridium(III) chloride penta-hydrate], represents the conjugate CH acid of 2.
The ligand [CH(dppm)2]+ is coordinated in a meridional manner. In the cationic
six-coordinate IrIII complex 4, [IrClH(CO)(C51H44P4)]Cl.2CH3OH.H2O or
[IrClH(CO)(C(dppm)2-kappa3P,C,P)]Cl.2CH3OH.H2O [systematic name: carbonyl
chlorido-hydrido(1,1,3,3,5,5,7,7-octa-phenyl-1,5lambda5,7-triphospha-3-phos-pho
niahept-4-en-4-yl)iridium(III) chloride-methanol-water (1/2/1)], the chlorido
ligand is found in the plane defined by the Ir center and the meridional PCP
ligand; the H and CO ligands are positioned axially to this plane and trans to
each other.
PMID- 29951244
TI - Crystal structure of racemic 2-[(beta-arabino-pyran-osyl)-sulfanyl]-4,6
diphenylpyridine-3-carbo-nitrile.
AB - In the racemic title compound, C23H20N2O4S, the sulfur atom is attached
equatorially to the sugar ring with unequal S-C bonds, viz.: S-Cs = 1.808 (2) and
S-Cp = 1.770 (2) A (s = sugar, p = pyrid-yl). The dihedral angles between the
pyridine ring and its attached phenyl groups are 42.24 (8) and 6.37 (14) degrees
. In the crystal, a system of classical O-H?O and O-H?(O,O) hydrogen bonds links
the mol-ecules to form tube-like assemblies propagating parallel to the c-axis
direction. Weak C-H?N inter-actions are also observed.
PMID- 29951245
TI - The crystal structures of iron and cobalt pyridine (py)-sulfates, [Fe(SO4)(py)4]
n and [Co3(SO4)3(py)11] n.
AB - The solid-state structures of two metal-pyridine-sulfate compounds, namely catena
poly[[tetra-kis-(pyridine-kappaN)iron(II)]-MU-sulfato-kappa2O:O'],
[Fe(SO4)(C5H5N)4] n , (1), and catena-poly[[tetra-kis-(pyridine
kappaN)cobalt(II)]-MU-sulfato-kappa2O:O'-[tetra-kis-(pyridine-kappaN)cobalt(II)]
MU-sulfato-kappa3O,O':O''-[tris-(pyridine-kappaN)cobalt(II)]-MU-sulfato
kappa2O:O'], [Co3(SO4)3(C5H5N)11] n , (2), are reported. The iron compound (1)
displays a polymeric structure, with infinite chains of FeII atoms adopting octa
hedral N4O2 coordination environments that involve four pyridine ligands and two
bridging sulfate ligands. The cobalt compound (2) displays a polymeric structure,
with infinite chains of CoII atoms. Two of the three Co centers have an octa
hedral N4O2 coordination environment that involves four pyridine ligands and two
bridging sulfate ligands. The third Co center has an octa-hedral N3O3
coordination environment that involves three pyridine ligands, and two bridging
sulfate ligands with one sulfate chelating the cobalt atom.
PMID- 29951246
TI - The crystal structures of 3-O-benzyl-1,2-O-iso-propyl-idene-5-O-methane-sulfonyl
6-O-tri-phenyl-methyl-alpha-d-gluco-furan-ose and its azide displacement product.
AB - The effect of different leaving groups on the substitution versus elimination
outcomes with C-5 d-glucose derivatives was investigated. The stereochemical
configurations of 3-O-benzyl-1,2-O-iso-propyl-idene-5-O-methane-sulfonyl-6-O-tri
phenyl-methyl-alpha-d-gluco-furan-ose, C36H38O8S (3) [systematic name: 1
[(3aR,5R,6S,6aR)-6-benz-yloxy-2,2-di-methyl-tetra-hydro-furo[2,3-d][1,3]dioxol-5
yl)-2-(trit-yloxy)ethyl methane-sulfonate], a stable inter-mediate, and 5-azido-3
O-benzyl-5-de-oxy-1,2-O-iso-propyl-idene-6-O-tri-phenyl-methyl-beta-l-ido-furan
ose, C35H35N3O5 (4) [systematic name: (3aR,5S,6S,6aR)-5-[1-azido-2-(trit
yloxy)eth-yl]-6-benz-yloxy-2,2-di-methyl-tetra-hydro-furo[2,3-d][1,3]dioxole], a
substitution product, were examined and the inversion of configuration for the
azido group on C-5 in 4 was confirmed. The absolute structures of the mol-ecules
in the crystals of both compounds were confirmed by resonant scattering. In the
crystal of 3, neighbouring mol-ecules are linked by C-H?O hydrogen bonds, forming
chains along the b-axis direction. The chains are linked by C-H?pi inter-actions,
forming layers parallel to the ab plane. In the crystal of 4, mol-ecules are also
linked by C-H?O hydrogen bonds, forming this time helices along the a-axis
direction. The helices are linked by a number of C-H?pi inter-actions, forming a
supra-molecular framework.
PMID- 29951247
TI - Crystal structure of 1-[3,5-bis-(tri-fluoro-meth-yl)phen-yl]-2-bromo-ethan-1-one.
AB - The title compound, C10H5BrF6O, synthesized via continuous stirring of 3,5-bis
(tri-fluoro-meth-yl) aceto-phenone with bromine in an acidic medium and
concentrated under reduced pressure, crystallizes with four mol-ecules in the
unit cell (Z = 4) and one formula unit in the asymmetric unit. In the crystal,
mol-ecules are linked in a head-to-tail fashion into dimers along the b-axis
direction through weak C-H?Br and C-O?Csp2 inter-actions. C-H?O, C-F?pi and F?F
inter-actions are also observed.
PMID- 29951248
TI - Crystal structure of 2-{5-[2-(2-hy-droxy-phen-yl)diazen-1-yl]-1-methyl-pyrrol-2
yl}phenol methanol monosolvate.
AB - In the title azo-pyrrole compound, C17H15N3O2.CH3OH, the azo N=N bond adopts a
trans configuration and the pyrrole N and azo group are in an anti orientation.
The dihedral angles between the pyrrole ring and the two phenyl rings are 6.7 (3)
and 54.7 (3) degrees . In the crystal, a supra-molecular ring structure is formed
between two azo-pyrrole and two methanol solvent mol-ecules through four O-H?O
hydrogen bonds.
PMID- 29951249
TI - Dexamethasone implant in silicone oil: in vitro behavior.
AB - Background: To determine the effect of the silicone on the dexamethasone
intravitreal implant. Methods: Basic, experimental, prospective and transversal
study performed at the hospital "Nuestra Senora de la Luz" in Mexico City. One
dexamethasone implant was placed in a test tube with 4 mL of each tamponade
medium: 1000cS, 5000cS and heavy silicone oil; basic saline solution was used as
the control medium. Photographs were taken weekly for 12 months. 200 uL samples
were taken from each medium at 24 h, 1, 2 weeks and monthly for 12 months. ELISA
test was performed to quantify dexamethasone release in every sample. An
inflammatory stimulus was created and later exposed it to every sample in order
to test their anti-inflammatory capacity by cytokine analysis using cytometric
bead array. Statistically significant results were obtained with p < 0.05.
Results: Photographic follow-up showed disintegration of the implant in control
medium. Implants in silicone oil suffered no changes during follow-up.
Dexamethasone levels in control medium showed stability from month 2 to 12.
Silicone oil mediums showed irregular dexamethasone release during the 1 year
period. Dexamethasone in control medium had inhibitory effects on TNF-alpha
starting at 24 h (p < 0.001) and remained stable. Dexamethasone in 1000cS
silicone oil showed inhibitory effects from month 2 (p < 0.001) until month 6 (p
< 0.001). Implants in denser silicone oils showed no inhibitory effects in any of
the samples. Conclusions: Denser mediums altered the implant pharmacokinetics and
showed no anti-inflammatory effects even when concentrations were quantified at
levels similar to control medium in vitro.
PMID- 29951250
TI - Evaluation of global HIV/SIV envelope gp120 RNA structure and evolution within
and among infected hosts.
AB - Lentiviral RNA genomes contain structural elements that play critical roles in
viral replication. Although structural features of 5'-untranslated regions have
been well characterized, attempts to identify important structures in other
genomic regions by Selective 2'-Hydroxyl Acylation analyzed by Primer Extension
(SHAPE) have led to conflicting structural and mechanistic conclusions. Previous
approaches accounted neither for sequence heterogeneity that is ubiquitous in
viral populations, nor for selective constraints operating at the protein level.
We developed an approach that augments SHAPE with phylogenetic analyses and
applied it to investigate structure in coding regions (cRNA) within the HIV and
SIV envelope genes. Analysis of single-genome SHAPE data with phylogenetic
information from diverse lentiviral sequences argues against the conservation of
a putative global gp120 RNA structure but points to the existence of core RNA sub
structures. Our findings establish a framework for considering sequence
heterogeneity and protein function in de novo RNA structure inference approaches.
PMID- 29951251
TI - Uncemented short stems in primary total hip arthroplasty: The state of the art.
AB - Over the last two decades, several conservative femoral prostheses have been
designed. The goals of conservative stems include: the spearing of the
trochanteric bone stock; a more physiological loading in the proximal femur
reducing the risk of stress shielding; and to avoid a long stem into the
diaphysis preventing impingement with the femoral cortex and thigh pain.All stems
designed to be less invasive than conventional uncemented stems are commonly
named 'short stems'. However, this term is misleading because it refers to a
heterogeneous group of stems deeply different in terms of design, biomechanics
and bearing. In the short-term follow-up, all conservative stems provided
excellent survivorship. However, variable rates of complications were reported,
including stem malalignment, incorrect stem sizing and intra-operative
fracture.Radiostereometric analysis (RSA) studies demonstrated that some
conservative stems were affected by an early slight migration and rotation within
the first months after surgery, followed by a secondary stable fixation. Dual
energy x-ray absorptiometry (DEXA) studies demonstrated an implant-specific
pattern of bone remodelling.Although the vast majority of stems demonstrated a
good osseointegration, some prostheses transferred loads particularly to the
lateral and distal-medial regions, favouring proximal stress shielding and bone
atrophy in the great trochanter and calcar regions. Cite this article: EFORT Open
Rev 2018;3:149-159. DOI: 10.1302/2058-5241.3.170052.
PMID- 29951252
TI - Research methodology for orthopaedic surgeons, with a focus on outcome.
AB - Since improving the patient's condition is the ultimate goal of clinical care and
research, this review of research methodology focuses on outcomes in the
musculoskeletal field.This paper provides an overview of conceptual models,
different types of outcomes and commonly assessed outcomes in orthopaedics as
well as epidemiological and statistical aspects of outcomes determination,
measurement and interpretation.Clinicians should determine the outcome(s) most
important to patients and/or public health in collaboration with the patients,
epidemiologists/statisticians and other stakeholders.Key points in outcome choice
are to evaluate both the benefit and harm of a health intervention, and to
consider short- and longer-term outcomes including patient-reported
outcomes.Outcome estimation should aim at identifying a clinically important
difference (not the same as a statistically significant difference), at
presenting measures of effects with confidence intervals and at taking the
necessary steps to minimize bias. Cite this article: EFORT Open Rev 2018;3 DOI:
10.1302/2058-5241.3.170064.
PMID- 29951253
TI - New advances in intra-operative imaging in trauma.
AB - The invention of flat-panel detectors led to a revolution in medical imaging. The
major benefits of this technology are a higher image quality and dose reduction.
Flat-panel detectors have proved to be superior to standard C-arms (= C-arm with
radiograph source and image intensifier).Cone-beam computed tomography (cone-beam
CT) is a 3D data set, which can be acquired with a flat-panel detector. The cone
shaped beam is used for 3D data generation. For cone-beam CT acquisition, the
flat-panel detector rotates around the patient lying on the operating table.
Intra-operative cone-beam CT can be a very helpful tool in orthopaedic surgery.
Immediate control of fracture reduction and implant positioning in high image
quality can reduce the need for secondary revision surgery due to implant
malposition.In recent years there has been a revival of standard fan beam CT
technology in operating rooms. Fixed and mobile systems are available. Fixed
systems are typically placed on a sliding gantry. Different mobile intra
operative CT scanners were recently introduced. Due to their mobility, they are
not bound to a specific operating room. The use of standard intra-operative CT
scanners results in high 3D image quality but, in comparison with a cone-beam CT
scanner, fluoroscopy is not possible.The introduction of flat-panel detectors has
led to improvements in intra-operative image quality combined with dose
reduction. The possibility of high-quality 3D imaging in combination with
navigation can assure optimal implant placement. Due to immediate control of the
osteosynthesis, revision surgery at a later time can be prevented. Cite this
article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170055.
PMID- 29951255
TI - Research methodology: how to maximize your research potential.
AB - Scientific education and a clinical background allow orthopaedic surgeons to
perform leading research. Several resources, skills and techniques may be
developed to maximize their research potential.Surgeon-researchers should develop
Specific, Measurable, Achievable, Realistic, and Time-defined (SMART) goals. It
is critical to define a timeline - which can be 1 year, 3 years, 5 years - to re
evaluate goals and to plan and identify potential obstacles.Physician-scientists
are a product of training, funding, resources, practice setting, context,
environment, and infrastructure. Although orthopaedic surgery has difficulty in
recruiting surgeon-scientists, these are essential for the promotion of advances
in technologies and treatment, as they have unique abilities to raise questions
from the bedside and the operating room.The most critical personal traits
necessary to succeed as a surgeon-scientist are persistence, resilience, and
passion for research. These traits may be innate or acquired through mentorship
and from role models.Mentors can improve mentees' research efficiency and help
them to persevere.Clinical researchers and surgeon-scientists should focus their
research interests and efforts in their areas of clinical expertise.For surgeon
researchers to succeed they must have passion for research, persistence in
working toward a goal, collaboration/teamwork skills, resilience, research
training/experience, a track record of publications, clear goals and
expectations, and a defined research plan as well as being clinically excellent.
A formal research degree is desirable.Having non-clinician scientists in the team
brings added expertise and value.Funding and protected research time are
important. To provide outstanding clinical care and improve the quality of the
care delivered, surgeons must be leaders in innovation and research. Cite this
article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170065.
PMID- 29951256
TI - Current trends in the management of degenerative lumbar spondylolisthesis.
AB - Degenerative spondylolisthesis (DS) is a common disease of the degenerative
spine, often associated with lumbar canal stenosis. However, the choice between
the different medical or surgical treatments remains under debate.Preference for
surgical strategy is based on the functional symptoms, and when surgical
treatment is selected, several questions should be posed and the surgical
strategy adapted accordingly.One of the main goals of surgery is to improve
neurological symptoms. Therefore, radicular decompression may be necessary.
Radicular decompression can be performed indirectly through interbody fusion or
interspinous spacer. However, indirect decompression has some limits, and the
most frequent technique is a posterior decompression with fusion.Indeed, in cases
of DS, associated fusion or dynamic stabilization are recommended to improve
functional outcomes and prevent future destabilization. Risk factors for
destabilization, such as anteroposterior and angular mobility, and significant
disc height, have been discussed in the literature. When fusion is performed,
osteosynthesis is often associated. It is essential to choose the length and
position of the fusion according to the pelvic incidence and global alignment of
the patient. It is possible to add interbody fusion to the posterolateral
arthrodesis to improve graft area and stability, increase local lordosis and open
foramina.The most common surgical treatment for DS is posterior decompression
with instrumented fusion. Nevertheless, some cases are more complicated and it is
crucial to consider the patient's general health status, symptoms and alignment
when selecting the surgical strategy. Cite this article: EFORT Open Rev 2018;3
DOI: 10.1302/2058-5241.3.170050.
PMID- 29951254
TI - Bioceramics and bone healing.
AB - Calcium phosphates have long been used as synthetic bone grafts. Recent studies
have shown that the modulation of composition and textural properties, such as
nano-, micro- and macro-porosity, is a powerful strategy to control and
synchronize material resorption and bone formation.Biomimetic calcium phosphates,
which closely mimic the composition and structure of bone mineral, can be
produced using low-temperature processing routes, and offer the possibility to
modulate the material properties to a larger extent than conventional high
temperature sintering processes.Advanced technologies open up new possibilities
in the design of bioceramics for bone regeneration; 3D-printing technologies, in
combination with the development of hybrid materials with enhanced mechanical
properties, supported by finite element modelling tools, are expected to enable
the design and fabrication of mechanically competent patient-specific bone
grafts.The association of ions, drugs and cells allows leveraging of the
osteogenic potential of bioceramic scaffolds in compromised clinical situations,
where the intrinsic bone regeneration potential is impaired. Cite this article:
EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170056.
PMID- 29951257
TI - Current concepts in the primary management of irreparable posterosuperior rotator
cuff tears without arthritis.
AB - Various procedures exist for patients with irreparable posterosuperior rotator
cuff tears (IRCT). At present, no single surgical option has demonstrated
clinical superiority.There is no panacea for treatment and patients must be
aware, in cases of palliative or non-prosthetic options, of an alarming rate of
structural failure (around 50%) in the short term.The current review does not
support the initial use of complex and expensive techniques in the management of
posterosuperior IRCT.Further prospective and comparative studies with large
cohort populations and long-term follow-up are necessary to establish
effectiveness of expensive or complicated procedures such as superior capsular
reconstruction (SCR), subacromial spacers or biological augmentation as reliable
and useful alternative treatments for IRCT. Cite this article: EFORT Open Rev
2018;3 DOI: 10.1302/2058-5241.3.180002.
PMID- 29951258
TI - Post-traumatic stiff elbow.
AB - Post-traumatic and post-operative stiffness of the elbow joint is relatively
common and may in pronounced cases markedly interfere with normal upper extremity
function.Soft-tissue contractures and heterotopic bone formation are two major
causes of limited movement.Extensive recent research has elucidated many of the
pathways contributing to these conditions, but the exact mechanisms are still
unknown.In the early phase of soft-tissue contractures conservative treatment may
be valuable, but in longstanding cases operative treatment is often
necessary.Several different options are available depending on the severity of
the condition and the underlying offending structures. Surgical treatment may
allow significant gains in movement but rarely complete restoration, and
complications are not uncommon.The following presentation reviews the recent
literature on pathomechanisms and treatment alternatives. Cite this article:
EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170062.
PMID- 29951259
TI - Bearing surfaces in primary total hip arthroplasty.
AB - Total hip arthroplasty (THA) is widely considered one of the most successful
surgical procedures in orthopaedics. It is associated with high satisfaction
rates and significant improvements in quality of life following surgery. On the
other hand, the main cause of late revision is osteolysis and wear, often a
result of failure of bearing surfaces.Currently, several options are available to
the surgeon when choosing the bearing surface in THA (ceramic-on-ceramic (CoC),
ceramic-on-polyethylene (CoPE), metal-on-polyethylene (MoPE)), each with
advantages and drawbacks.Very few studies have directly compared the various
combinations of bearings at long-term follow-up. Randomized controlled trials
show similar short- to mid-term survivorship among the best performing bearing
surfaces (CoC, CoXLPE and MoXLPE). Selection of the bearing surface is often
'experience-based' rather than 'evidence-based'.The aim of this paper is
therefore to evaluate the main advantages and drawbacks of various types of
tribology in THA, while providing practical suggestions for the surgeon on the
most suitable bearing surface option for each patient. Cite this article: EFORT
Open Rev 2018;3 DOI: 10.1302/2058-5241.3.180300.
PMID- 29951261
TI - Total hip arthroplasty: Survival and modes of failure.
AB - Total hip arthroplasty (THA) is a very satisfactory surgical procedure for end
stage hip disorders.Implant modifications, such as large femoral heads to improve
stability, porous metals to enhance fixation and alternative bearings to improve
wear, have been introduced over the last decade in order to decrease the rate of
early and late failures.There is a changing pattern of THA failure modes.The
relationship between failure modes and patient-related factors, and the time and
type of revision are important for understanding and preventing short and late
failure of implants.The early adoption of innovations in either technique or
implant design may lead to an increased risk of early failure. Cite this article:
EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170068.
PMID- 29951260
TI - Head size in primary total hip arthroplasty.
AB - The use of larger femoral head size in total hip arthroplasty (THA) has increased
during the past decade; 32 mm and 36 mm are the most commonly used femoral head
sizes, as reported by several arthroplasty registries.The use of large femoral
heads seems to be a trade-off between increased stability and decreased THA
survivorship.We reviewed the literature, mainly focussing on the past 5 years,
identifying benefits and complications associated with the trend of using larger
femoral heads in THA.We found that there is no benefit in hip range of movement
or hip function when head sizes > 36 mm are used.The risk of revision due to
dislocation is lower for 36 mm or larger bearings compared with 28 mm or smaller
and probably even with 32 mm.Volumetric wear and frictional torque are increased
in bearings bigger than 32 mm compared with 32 mm or smaller in metal-on-cross
linked polyethylene (MoXLPE) THA, but not in ceramic-on-XLPE (CoXLPE).Long-term
THA survivorship is improved for 32 mm MoXLPE bearings compared with both larger
and smaller ones.We recommend a 32 mm femoral head if MoXLPE bearings are used.
In hips operated on with larger bearings the use of ceramic heads on XLPE appears
to be safer. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058
5241.3.170061.
PMID- 29951262
TI - Trochlear dysplasia: imaging and treatment options.
AB - Recurrent patellar dislocation is a disabling condition, which can lead to
articular cartilage injuries, osteochondral fractures, recurrent instability,
pain, decreased activity and patellofemoral osteoarthritis. Trochlear dysplasia
represents an important component of patellar dislocation.Imaging provides an
objective basis for the morphological abnormalities and thus allows determination
of the surgical strategy according to the concept of 'a la carte' surgery.The
main surgical techniques of trochleoplasty are the sulcus deepening
trochleoplasty, the 'Bereiter' trochleoplasty and the recession trochleoplasty.At
mid-term, all techniques have shown a postoperative improvement in clinical
scores, with a low rate of recurrence of dislocation and a possible return to
sport. But these techniques do not halt the progression of patellofemoral
arthritis. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058
5241.3.170058.
PMID- 29951263
TI - 3D printing and unicompartmental knee arthroplasty.
AB - In suitable patients, unicompartmental knee arthroplasty (UKA) offers a number of
advantages compared with total knee arthroplasty. However, the procedure is
technically demanding, with a small tolerance for error. Assistive technology has
the potential to improve the accuracy of implant positioning.This review paper
describes the concept of detailed UKA planning in 3D, and the 3D printing
technology that enables a plan to be delivered intraoperatively using patient
specific instrumentation (PSI).The varying guide designs that enable accurate
registration are discussed and described. The system accuracy is reported.Future
studies need to ascertain whether accuracy for low-volume surgeons can be
delivered in the operating theatre using PSI, and reflected in improved patient
reported outcome measures, and lower revision rates. Cite this article: EFORT
Open Rev 2018;3 DOI: 10.1302/2058-5241.3.180001.
PMID- 29951264
TI - 3D printing and high tibial osteotomy.
AB - High tibial osteotomy (HTO) is a relatively conservative surgical option in the
management of medial knee pain. Thus far, the outcomes have been variable, and
apparently worse than the arthroplasty alternatives when judged using
conventional metrics, owing in large part to uncertainty around the extent of the
correction planned and achieved.This review paper introduces the concept of
detailed 3D planning of the procedure, and describes the 3D printing technology
that enables the plan to be performed.The different ways that the osteotomy can
be undertaken, and the varying guide designs that enable accurate registration
are discussed and described. The system accuracy is reported.In keeping with
other assistive technologies, 3D printing enables the surgeon to achieve a
preoperative plan with a degree of accuracy that is not possible using
conventional instruments. With the advent of low dose CT, it has been possible to
confirm that the procedure has been undertaken accurately too.HTO is the
'ultimate' personal intervention: the amount of correction needed for optimal
offloading is not yet completely understood.For the athletic person with early
medial joint line overload who still runs and enjoys life, HTO using 3D printing
is an attractive option. The clinical effectiveness remains unproven. Cite this
article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170075.
PMID- 29951267
TI - Weight-bearing cone beam CT scans in the foot and ankle.
AB - The 3D anatomical complexity of the foot and ankle and the importance of weight
bearing in diagnosis have required the combination of conventional radiographs
and medical CT.Conventional plain radiographs (XR) have demonstrated substantial
limitations such as perspective, rotational and fan distortion, as well as poor
reproducibility of radiographic installations. Conventional CT produces high
levels of radiation exposure and does not offer weight-bearing capabilities.The
literature investigating biometrics based on 2D XR has inherent limitations due
to the technology itself and thereby can focus only on whether measurements are
reproducible, when the real question is whether the radiographs are.Low dose
weight-bearing cone beam CT (WBCT) combines 3D and weight-bearing as well as
'built in' reliability validated through industry-standardized processes during
production and clinical use (quality assurance testing).Research is accumulating
to validate measurements based on traditional 2D techniques, and new 3D
biometrics are being described and tested.Time- and cost-efficient use in medical
imaging will require the use of automatic measurements. Merging WBCT and clinical
data will offer new perspectives in terms of research with the help of modern
data analysis techniques. Cite this article: EFORT Open Rev 2018;3 DOI:
10.1302/2058-5241.3.170066.
PMID- 29951265
TI - Modern treatment of meniscal tears.
AB - The complex ultrastructure of the meniscus determines its vital functions for the
knee, the lower extremity, and the body.The most recent concise, reliable, and
valid classification system for meniscal tears is the International Society of
Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS)
Classification, which takes into account the subsequent parameters: tear depth,
tear pattern, tear length, tear location/rim width, radial location, location
according to the popliteal hiatus, and quality of the meniscal tissue.It is the
orthopaedic surgeon's responsibility to combine clinical information,
radiological images, and clinical experience in an effort to individualize
management of meniscal tears, taking into account factors related to the patient
and lesion.Surgeons should strive not to operate in most cases, but to protect,
repair or reconstruct, in order to prevent early development of osteoarthritis by
restoring the native structure, function, and biomechanics of the
meniscus.Currently, there are three main methods of modern surgical management of
meniscus tears: arthroscopic partial meniscectomy; meniscal repair with or
without augmentation techniques; and meniscal reconstruction. Meniscus surgery
has come a long way from the old slogan, "If it is torn, take it out!" to the
currently accepted slogan, "Save the meniscus!" which has guided evolving modern
treatment methods for meniscal tears. This last slogan will probably constitute
the basis for newer alternative biological treatment methods in the future. Cite
this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170067.
PMID- 29951268
TI - Treatment strategies for early-onset scoliosis.
AB - Early-onset scoliosis (EOS) is defined as a spinal deformity occurring before the
age of ten years.Untreated EOS or early spinal fusion resulting in a short spine
is associated with increased mortality and cardiopulmonary compromise.EOS may
progress rapidly, and therefore prompt clinical diagnosis and referral to a
paediatric orthopaedic or spine unit is necessary.Casting under general
anaesthesia can be effective and may prevent or delay the need for surgery in
curves of less than 60 degrees .'Growing' rods (traditional or magnetically
controlled) represent the standard surgical treatment in progressive curves of 45
degrees or greater.Children with congenital scoliosis associated with fused ribs
benefit from surgery with a vertical titanium prosthetic rib.Surgery with growth
friendly instrumentation is associated with a high risk of complications. Cite
this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170051.
PMID- 29951266
TI - New trends in the orthopaedic management of diabetic foot.
AB - Although there are various types of therapeutic footwear currently used to treat
diabetic foot ulcers (DFUs), recent literature has enforced the concept that
total-contact casts are the benchmark.Besides conventional clinical tests and
imaging modalities, advanced MRI techniques and high-sensitivity nuclear medicine
modalities present several advantages for the investigation of diabetic foot
problems.The currently accepted principles of DFU care are rigorous debridement
followed by modern wound dressings to provide a moist wound environment.
Recently, hyperbaric oxygen and negative pressure wound therapy have aroused
increasing attention as an adjunctive treatment for patients with DFUs.For DFU,
various surgical treatments are currently available, including resection
arthroplasty, metatarsal osteotomies and metatarsal head resections.In the modern
management of the Charcot foot, surgery in the acute phase remains controversial
and under investigation. While conventional fixation techniques are frequently
insufficient to keep alignment postoperatively, superconstruct techniques could
provide a successful fixation.Retrograde intramedullary nailing has been a
generally accepted method of achieving stability. The midfoot fusion bolt is a
current treatment device that maintains the longitudinal columns of the foot.
Also, Achilles tendon lengthening remains a popular method in the management of
Charcot foot. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058
5241.3.170073.
PMID- 29951269
TI - Stability in ankle fractures: Diagnosis and treatment.
AB - Medial column (deltoid ligament) integrity is of key importance when considering
the stability of isolated lateral malleolus ankle fractures.Weight-bearing
radiographs are the best method of evaluating stability of isolated distal fibula
fractures.Computed tomography (CT) scanning is mandatory for the assessment of
complex ankle fractures, especially those involving the posterior malleolus.Most
isolated trans-syndesmotic fibular fractures (Weber-B, SER, AO 44-B) are stable
and can safely be treated non-operatively.Posterior malleolus fractures,
regardless of size, should be considered for surgical fixation to restore
stability, reduce the need for syndesmosis fixation, and improve contact pressure
distribution. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058
5241.3.170057.
PMID- 29951270
TI - Ischaemia, healing and outcomes in proximal humeral fractures.
AB - Interfragmental ischaemia is a prerequisite for the initiation of the
inflammatory and immunological response to fracturing of bone.Intrafragmental
ischaemia is inevitable: the extent of the initial ischaemic insult does not,
however, directly relate to the outcome for healing of the fracture zones and
avascular necrosis of the humeral head. The survival of distal regions of
fragments with critical perfusion may be the result of a type of inosculation
(blood vessel contact), which establishes reperfusion before either
revascularization or neo-angiogenesis has occurred.Periosteum has a poorly
defined role in fracture healing in the proximal humerus. The metaphyseal
periosteal perfusion may have a profound effect, as yet undefined, on the healing
of most metaphyseal fractures of the proximal humerus, and may be disturbed
further by inadvertent surgical manipulation.The metaphysis can be considered as
a 'torus' or ring of bone, its surface covered by periosteum antero- and
posterolaterally, through which the tuberosity segments gain perfusion and
capsular reflections antero- and posteromedially, through which the humeral head
(articular) fragment gains perfusion.The torus is broken in relatively simple
primary patterns: a fracture line at the upper surface of the torus is an
anatomical 'neck' fracture; a fracture line at the lower surface of the torus is
the surgical 'neck' fracture. Secondary fragmentation (through compression and/or
distraction) of the torus itself creates complexity for analysis
(classification), alters the capacity and outcome for healing (by variable
interruption of the fragmental blood supply) and influences interfragmental
stability. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058
5241.3.180005.
PMID- 29951271
TI - Open fractures of the lower extremity: Current management and clinical outcomes.
AB - Open fractures of the lower extremity are the most common open long bone
injuries, yet their management remains a topic of debate.This article discusses
the basic tenets of management and the subsequent impact on clinical outcome.
These include the rationale for initial debridement, antimicrobial cover,
addressing the soft-tissue injury and definitive skeletal management.The
classification of injury severity continues to be a useful tool in guiding
treatment and predicting outcome and prognosis. The Gustilo-Anderson
classification continues to be the mainstay, but the adoption of severity scores
such as the Ganga Hospital score may provide additional predictive utility.Recent
literature has challenged the perceived need for rapid debridement within 6 hours
and the rationale for prolonged antibiotic therapy in the open fracture. The
choice of definitive treatment must be decided against known efficacy and injury
severity/type.Recent data demonstrate better outcomes with internal fixation
methods in most open tibial fractures, but external fixation continues to be an
appropriate choice in more severe injuries. The incidence of infection and non
union has decreased with new treatment approaches but continues to be a source of
significant morbidity and mortality.Assessment of functional outcome using
various measures has been prevalent in the literature, but there is limited
consensus regarding the best measures to be used. Cite this article: EFORT Open
Rev 2018;3 DOI: 10.1302/2058-5241.3.170072.
PMID- 29951272
TI - Percutaneous fixation of acetabular fractures.
AB - The objective of surgery for acetabular fractures is to achieve precise reduction
to restore joint congruence, fix internal bone fragments, avoid displacement of
the fracture and allow rapid rehabilitation.Open reduction and internal fixation
is the benchmark method for displaced acetabular fractures, but open reductions
can increase morbidity, causing neurovascular injury, blood loss, heterotopic
bone formation, infection and poor wound healing.An anatomical reduction with a
gap of 2 mm or less is a predictor of good joint function and reduced risk of
post-traumatic osteoarthritis.The percutaneous approach is associated with fewer
complications than open techniques, but acetabular geometry makes percutaneous
screw insertion a challenging procedure.The percutaneous technique is recommended
for non-displaced or slightly displaced fractures, and in obese, osteoporotic and
elderly patients who cannot receive total joint arthroplasty.We recommend the use
of intramedullary cannulated screws.Fracture reductions are achieved by manual
traction of the affected bones. If some fracture displacement remains, accessory
windows can be used to introduce a ball spike pusher, a hook or a Steinmann pin
which can be used as a joystick to rotate the fracture.In this paper, we describe
the accessory windows for the anterior column, the quadrilateral plate and the
posterior column. We detail the position, direction and kind of screws used to
stabilize the anterior and posterior columns. Cite this article: EFORT Open Rev
2018;3 DOI: 10.1302/2058-5241.3.170054.
PMID- 29951273
TI - Pelvic post-traumatic asymmetry: Assessment and sequenced treatment.
AB - The most common cause of post-traumatic pelvic asymmetry is, by far, initial
nonoperative treatment.Open reduction and internal fixation of unstable pelvic
fractures are recommended to avoid pelvic nonunion or subsequent structural
deformities.The most common symptom is pelvic pain. Pelvic instability is another
symptom, as well as persistent urogenital problems and neurological
sequelae.Preoperative evaluation of these patients requires careful clinical and
functional assessment, in addition to a complete radiological study.Surgical
treatment of pelvic fracture nonunions is technically demanding and has
potentially serious complications.We have developed a new classification that
modifies and completes Mears and Velyvis's classification in which we highlight
two types of post-traumatic sequelae with different clinical conditions and whose
basic differentiating element is whether pelvic deformity is present or not.
Based on this classification, we have established our strategy of surgical
treatment. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058
5241.3.170069.
PMID- 29951274
TI - Safe management of acute cervical spine injuries.
AB - Cervical spine injuries are frequent and often caused by a blunt trauma
mechanism. They can have severe consequences, with a high mortality rate and a
high rate of neurological lesions.Diagnosis is a three-step process: 1) risk
assessment according to the history and clinical features, guided by a clinical
decision rule such as the Canadian C-Spine rule; 2) imaging if needed; 3)
classification of the injury according to different classification systems in the
different regions of the cervical spine.The urgency of treatment is dependent on
the presence of a neurological lesion and/or instability. The treatment strategy
depends on the morphological criteria as defined by the classification. Cite this
article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170076.
PMID- 29951275
TI - Frequently asked questions of individuals with spinal cord injuries: results of a
web-based consultation service in Iran.
AB - Study design: Descriptive study of the results of a web-based consultation
service for individuals with spinal cord injury (SCI). Objectives: To review
frequently asked questions (FAQ) among individuals with SCI and determine the
most important topics. Setting: Sina Trauma and Surgery Research Center, Tehran
University of Medical Sciences, Tehran, Iran. Methods: A cross-sectional study
reviewing questions from patients with SCI that were collected from the Health
and Safety Consultant Center (HSCC) between January and December 2015. The HSCC
is a web-based medical consultation service that provides patients with
information and counseling pertaining to SCI. Results: A total of 113 questions
were collected from 99 individuals. The mean age was 32.02 +/- 13.28 years with a
range of 3-70 years. Men accounted for 81.7% of the questions, while women
accounted for 18.3%. The most common site of SCI was thoracic (40.6%), followed
by lumbar (31.3%), and cervical (28.1%). Recovery potential (38.1%), sexual and
reproductive issues (26.5%), urinary (10.6%), and motor (10.6%) problems were
among the most commonly reviewed topics. Conclusions: FAQ provide insight on
areas of concerns for individuals with SCI and help guide providers to determine
high-yield topics. Discerning the specific areas of need or concern for patients
is instrumental in developing pertinent educational materials and programs, in
addition to efficiently counseling patients and caregivers on the aftercare of
SCI.
PMID- 29951276
TI - Weaning from long-term mechanical ventilation utilizing closed-loop ventilation
mode (IntelliVent(r)-ASV(r)) in a patient with spinal cord injury.
AB - Introduction: Cervical spinal cord injury with the C3 neurological level may
cause respiratory failure and require long-term mechanical ventilation.
Conventional weaning of spontaneous breathing trials is difficult to perform
outside of intensive care or spinal cord units. Case presentation: An 80-year-old
man presented with total tetraplegia and restrictive respiratory failure that
required assisted ventilation after a falling accident. Cervical spine magnetic
resonance imaging showed cervical cord compression that was worst at the C3-C4
intervertebral level. He experienced unexpected cardiac arrest during the
conventional weaning process of trials of intermittent spontaneous breathing in
the intensive care unit. The automated weaning protocol utilizing a closed-loop
ventilation mode (IntelliVent(r)-ASV (r) ) was introduced 131 days after injury
in our ward for chronically ill patients. The patient was successfully weaned 39
days after the introduction of the weaning protocol. Discussion: An automated
weaning protocol utilizing a closed-loop ventilation mode could be an optional
procedure in patients with cervical cord injury on long-term mechanical
ventilation, even in a ward for chronically ill patients where sufficient staff
is not available. The efficacy and safety, and the cost-effectiveness of the
procedure should be examined in larger spinal cord units.
PMID- 29951277
TI - Neurophysiological monitoring of displaced odontoid fracture reduction in a 3
year-old male.
AB - Introduction: Odontoid fractures in young children are rare. Most authors
advocate for closed reduction and external stabilization as first line treatment.
Unlike adults, young children are much less amenable to an awake reduction for
real-time assessment of neurological function. We used spinal cord monitoring, as
used in spine surgery, to assess the function of the spinal cord during the
closed reduction in our 31-month-old patient. Case presentation: A 31-month-old
male presented with a displaced odontoid fracture and ASIA C spinal cord injury.
Given his age, closed reduction and halo application were completed under general
anesthesia guided by neuromonitoring. A less-than-ideal reduction initially was
accepted due to a decline in motor-evoked potentials. Subsequently, there was no
change in neurological status. The reduction was repeated under anesthesia, with
monitoring, a number of times until good correction was achieved. Ultimately, a
surgical fusion was required due to ligamentous instability. The child achieved a
very good neurological outcome and a stable spine. Discussion: Neuromonitoring is
an important adjunct to closed reductions when complete and reliable neurological
assessment is not possible.
PMID- 29951278
TI - Awards and updates.
PMID- 29951279
TI - The role of spirituality in spinal cord injury (SCI) rehabilitation: exploring
health professional perspectives.
AB - Study design: Descriptive, qualitative study. Objectives: To explore the
perspectives of health professionals (HPs) regarding the role of spirituality in
spinal cord injury (SCI) rehabilitation. Setting: Single centre rehabilitation
hospital, NSW, Australia. Methods: Two focus groups (n = 12) were conducted with
HPs (e.g., nursing, allied health, medical) working in SCI inpatient
rehabilitation. A semi-structured interview was employed, consisting of questions
about spirituality and its role in SCI rehabilitation. The groups were audio
recorded and transcribed. An inductive thematic analysis was conducted. Results:
Six themes were identified from the focus group data: (i) the meaning of
spirituality; (ii) spirituality as a help; (iii) spirituality as a hindrance;
(iv) how spirituality is indirectly addressed in practice; (v) perceived barriers
to incorporating spirituality into practice; (vi) how spirituality can be better
integrated into practice. HPs recognised that spirituality played an important
role in the adjustment of many individuals and their families after SCI. However,
spirituality was not proactively addressed during SCI rehabilitation, and most
often arose during informal interactions with clients. Spirituality, and
specifically religious belief, was perceived to sometimes raise difficulties for
clients and staff. The use of physical space and a review of rehabilitation
processes were suggested by HPs as two ways spirituality could be better
incorporated into practice. Conclusions: The findings of this study reveal that
spiritual needs of clients and their family members during SCI rehabilitation are
important and could be better addressed. A range of initiatives are proposed,
including staff training and the use of standardised spiritual assessment tools.
PMID- 29951280
TI - Soft tissue sarcoma affecting the right shoulder of a man with paraplegia from a
remote traumatic spinal cord injury: a case report.
AB - Introduction: People with spinal cord injury (SCI) are getting older due to a
combination of increased life expectancy and older age at the time of injury.
This trend makes it more likely for these patients to have other chronic health
conditions including cancer. Inevitably relatively rare cancers such as soft
tissue sarcomas (STS), which are more common with advancing age, will occur in
some SCI patients. The present case represents the first report of a limb STS in
a patient with chronic paraplegia from a traumatic SCI. Case presentation: We
report a case of a 50-year-old right handed male with a T6 chronic, complete SCI
(American Spinal Injury Association Impairment Scale A) who presented with a
large mass involving his right shoulder musculature that was determined to be a
high grade spindle cell sarcoma. The patient was followed closely by Physiatry
over an approximately 6-month time course including prior to his tumor diagnosis,
during the pre-radiation and pre-surgical planning phase, and then post
operatively for his acute inpatient rehabilitation. He was successfully
discharged home to live alone in his accessible apartment complex. Discussion:
This case is the first ever reported case of a person living with a traumatic SCI
who subsequently developed a limb STS. In addition to its novelty, this case
illustrates how health conditions such as rare cancers are presenting more often
as the chronic SCI population is getting older, which creates both unique
diagnostic and management challenges for cancer rehabilitation specialists.
PMID- 29951281
TI - Long-term reduction in hyperglycemia in advanced type 1 diabetes: the value of
induced aerobic glycolysis with BCG vaccinations.
AB - Mycobacterium are among the oldest co-evolutionary partners of humans. The
attenuated Mycobacterium bovis Bacillus Calmette Guerin (BCG) strain has been
administered globally for 100 years as a vaccine against tuberculosis. BCG also
shows promise as treatment for numerous inflammatory and autoimmune diseases.
Here, we report on a randomized 8-year long prospective examination of type 1
diabetic subjects with long-term disease who received two doses of the BCG
vaccine. After year 3, BCG lowered hemoglobin A1c to near normal levels for the
next 5 years. The BCG impact on blood sugars appeared to be driven by a novel
systemic and blood sugar lowering mechanism in diabetes. We observe a systemic
shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis,
a state of high glucose utilization. Confirmation is gained by metabolomics,
mRNAseq, and functional assays of cellular glucose uptake after BCG vaccinations.
To prove BCG could induce a systemic change to promote accelerated glucose
utilization and impact blood sugars, murine data demonstrated reduced blood
sugars and aerobic induction in non-autoimmune mice made chemically diabetic. BCG
via epigenetics also resets six central T-regulatory genes for genetic re
programming of tolerance. These findings set the stage for further testing of a
known safe vaccine therapy for improved blood sugar control through changes in
metabolism and durability with epigenetic changes even in advanced Type 1
diabetes.
PMID- 29951282
TI - Predictors of circulating INTERLEUKIN-6 levels in head and neck cancer patients.
AB - Background: Circulating interleukin-6 (IL-6) improves outcome prediction for
second primary cancer (SPC) in head and neck cancer (HNC) patients. This study
aimed to identify factors associated with IL-6 serum levels in HNC patients.
Methods: This study was conducted as part of a phase III chemoprevention trial.
IL-6 was measured using chemiluminescent immunometric assay on pretreatment serum
sample obtained from 527 stage I-II HNC patients. Patients' lifestyle habits,
sociodemographic, medical and tumor characteristics were evaluated before
radiation therapy (RT). Factors independently associated with IL-6 levels before
RT were identified using multiple linear regression. Results: The median IL-6
serum level was 3.1 ng/L. In the multivariate analysis, eight factors were
significantly associated (p < 0.05) with IL-6: age, gender, marital status, body
mass index, tobacco consumption, comorbidities, Karnofsky Performance Status and
HNC site. Smoking duration and lifetime pack-years were positively associated
with IL-6 serum levels in a dose-response relationship (p-value for trend
<=0.03). Conclusions: Circulating IL-6 is a strong predictor of the occurrence of
SPC in HNC patients. We identified eight factors independently associated with
serum IL-6 levels in 527 stage I-II HNC patients.The dose-response relationship
between lifetime smoking and IL-6 serum levels suggested a causal role of tobacco
exposure on IL-6 production. Further studies are needed to establish whether the
effect of tobacco exposure on SPC could be partly mediated by IL-6, a pro
inflammatory cytokine.
PMID- 29951283
TI - The effects of resistance and endurance training on risk factors of vascular
inflammation and atherogenesis in non-athlete men.
AB - Background: Studies show that different types of training have a significant role
in reducing both new and traditional risk factors of cardiovascular diseases, and
the new risk factors are more sensitive and accurate in predicting such diseases.
Objective: The aim of this study was to determine the effects of resistance and
endurance exercises on risk factors of vascular inflammation and atherogenesis in
non-athlete men. Methods: Thirty-six non-athlete male students (mean age: 20.45
+/- 1.20 years; mean body mass index: 23.66 +/- 3.65 kg/m2) were randomly
assigned into either three groups: control group, resistance training (RT), and
endurance training (ET). The training groups exercised for 3 days/week for 8
weeks. ET group performed treadmill-running at 65%-80% of maximum heart rate and
with a 16-30 min duration; the task of RT group consisted of three repetition
sets, 8-10 per set, at 60%-80% of one repetition maximum, with 2-min recesses.
Blood samples were taken before and after the training program. Data were
analyzed by Shapiro-Wilk test, one-way ANOVA, LSD test, and dependent t-test
(alpha <= 0.05). Results: The results indicated a significant reduction in total
cholesterol levels in both RT and ET groups. Also high-density lipoprotein
cholesterol significantly increased in both training groups. In addition,
following 8 weeks, low-density lipoprotein cholesterol in ET group was
significantly decreased, whereas these training methods have had no significant
effects on the new cardiovascular biomarkers (hs-CRP, IL-6, and sICAM-1).
Conclusion: It seems that both ET and RT with improvement in lipid profiles could
be effective in prevention and treatment of the cardiovascular disease.
PMID- 29951284
TI - Diode laser therapy in the management of chronic periodontitis - A clinico
microbiological study.
AB - Introduction: Chronic periodontitis (CP) is an infectious disease resulting in
inflammation of the supporting tissues of the teeth with progressive attachment
loss and bone loss. This study aimed to evaluate the effect of 980-nm diode
laser, as an adjunct to scaling and root planing (SRP) in the management of CP.
Methodology: A total of 40 systemically healthy subjects diagnosed with CP were
randomly assigned into two groups G1 (SRP and sham application of laser) and G2
(SRP and laser irradiation) with equal numbers in each. The levels of
Porphyromonas gingivalis (Pg) were estimated from plaque samples using real-time
polymerase chain reaction. Clinical and microbiological parameters were assessed
at baseline, 4-6, and 12-14 weeks posttreatment in both groups. Results: A
gradual reduction in the levels of Pg and improvement in clinical parameters were
observed from baseline to 4-6 and 12-14 weeks in both groups. However, the
comparison between groups, although clinically relevant, was not found to be
statistically significant. Conclusion: Although a 980-nm diode laser may not have
any added benefit compared with SRP, it may emerge as an effective non-surgical
treatment option in advanced periodontitis with complex inaccessible subgingival
niches where comprehensive periodontal care may not be feasible.
PMID- 29951285
TI - Salivary oxidative analysis and periodontal status in children with atopy.
AB - Background and aims: Prevalence of atopic diseases is progressively increasing in
children with unclear clinical picture in oral cavity. This study aimed to find
correlation between the total antioxidant and periodontal status in the saliva of
periodontally compromised with atopy. Materials and methods: The groups consisted
of patients of atopic diseases and gingivitis (ADG), of atopic diseases without
gingivitis (AD), and healthy controls (HC). The level of gingival inflammation
was evaluated using the sulcus bleeding index (SBI) reported by Muhlemann and
Son. Glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD)
were estimated in saliva. Results: The mean salivary MDA levels of group HC was
significantly lower compared with group ADG and AD (P < 0.05). Similarly, in the
case of salivary GSH, marker levels revealed a significant decrease (P < 0.05)
when mean values in the control group (5.12 +/- 0.66 umol/L) were compared with
the ADG (2.31 +/- 0.44 umol/L) and AD groups (2.69 +/- 0.56 umol/L). The SOD
activity was significantly lower in the ADG and AD groups compared with HC.
Discussion: As there was no significant difference in the level of SOD
concentration between groups, we suggest that antioxidant imbalance is primarily
explained by atopic disease. Conclusion: The results showed changes in
antioxidant balance in children with atopy.
PMID- 29951286
TI - Report on the management of thrombocytopenia in obstetric patients: A
retrospective study.
AB - Thrombocytopenia occurs to approximately 8%-10% of pregnant women and this
condition is a notable source of morbidity and mortality during pregnancy. In the
recent years, our comprehension of thrombocytopenia has progressed on pregnancy.
Nevertheless, there has not been adequate information about thrombocytopenia
outcomes in obstetric patients. With regard to this topic, we reviewed published
reports as an update from the managements on these cases. Nevertheless,
recommendations for management of delivery in obstetric women with
thrombocytopenia are based on several hypotheses requiring critical analysis. For
this cause, we reviewed the management of pregnant patients with thrombocytopenia
treated over a period of 37 years.
PMID- 29951287
TI - A rare complication of percutaneous coronary intervention: Coronary
pseudoaneurysm formation.
AB - Coronary pseudoaneurysms (CPAs) are rare complications developed after
percutaneous coronary interventions. They may cause stent thrombosis, distal
embolization, and coronary rupture leading to cardiac tamponade. Therefore, high
risk CPA should be promptly treated after diagnosis. They can be managed with
percutaneous or surgical intervention. Herein, we aimed to present a patient who
developed CPA 3 weeks after percutaneous coronary intervention and successfully
treated with percutaneous intervention using a covered stent.
PMID- 29951288
TI - A bedside ultrasound technique for fluid therapy monitoring in severe
hypovolemia: Tissue Doppler imaging of the right ventricle.
AB - Fluid therapy is one of the main issues for hemodynamic resuscitation. Tissue
Doppler imaging (TDI) of the right ventricle (RV) with bedside ultrasound (BUS)
technique is a new dynamic method to identify fluid responsiveness in patients
with hypotension. Here, we present the case of a hypotensive patient monitored
with TDI measurements of RV. A 75-year-old male patient was admitted to the
emergency department (ED) with the complaint of diarrhea. He was in severe
hypovolemia, with hypotension, tachycardia, and tachypnea. His laboratory results
were normal. BUS was performed on the patient by the ED physician. The velocity
of the excursion of the tricuspid valve measured at presentation was 14.47 cm/s
and, together with collapsed inferior vena cava (IVC), this finding led to the
decision to begin fluid therapy immediately. The patient underwent 2 L of fluid
therapy with 0.9% NaCl in a 2-h period. Control BUS after fluid therapy revealed
decreased TDI velocity of tricuspid annulus to 11.81 cm/s and dilated IVC not
collapsing sufficiently with respiration. The patient received his maintenance
therapy after admission to the internal medicine department and was discharged
from the service after 3 days. TDI in fluid responsiveness may find a clinical
role in the future by the clinical studies.
PMID- 29951289
TI - Transvaginal extraction of laparoscopic liver resection specimen.
AB - The application of laparoscopic surgery via the vagina has been introduced at the
beginning of this millennium. Here, we report a case of transvaginal extraction
of a laparoscopic hepatectomy specimen. An exophytic liver mass originated from
segment VI in a 24-year-old female was excised with laparoscopic technique using
four trocars (0.5-1.2 cm sizes). The specimen (11 * 8.5 cm) was removed
transvaginally instead of an abdominal incision. To the best of our knowledge,
only six similar cases have been previously reported, with a patient age range of
32-74 years. Our case, due to younger age, had high cosmetic expectations.
Specific to this case, we aimed a better aesthetic outcomes and better
convalescence period and, we achieved these objectives. We believe that patient
selection and experience on natural orifice specimen extraction were the keys to
the success of the operation. We shared this technique with a video presentation.
PMID- 29951290
TI - Oxidative modification of proteins in the process of experimental periodontitis
development.
AB - The article reveals patterns of changes in the parameters of oxidative
modification of proteins for different periods of the inflammatory process in
periodontal tissues during periodontitis. Biochemical researches of
phenylhydrazones, aldehyde-, and ketone derivatives of neutral and basic proteins
were determined in the blood of white rats on the 7th, 14th, and 30th days of the
experimental periodontitis development, as well as in intact animals. The method
for determination of the oxidative modification of proteins was based on the
interaction of oxidized amino acid residues with 2,4-dinitrophenylhydrazine to
form 2,4-dinitrophenylhydrazones. At the early stage of experimental
periodontitis development, i.e., on the 7th day, an increase in the products of
oxidative modification of proteins of basic and neutral nature was observed in
the blood serum, but later, on the 14th day, this index changed in opposite
direction, i.e., it began to decrease; however, it was higher relative to the
intact group of animals. The obtained factual data evidence that under the
conditions of experimental periodontitis formation, there is an intensive
increase in the level of oxidative modification of proteins especially in the
early period of the inflammatory process development.
PMID- 29951291
TI - Nano-colloidal carrier via polymeric coating for oral delivery of isradipine.
AB - Our research objective was to develop, characterize, and optimize stable form of
nano-colloidal carrier with Eudragit-coated solid lipid nanobioparticles (SLNbp)
for oral delivery of isradipine (ISR). To achieve, a three factors, i.e., lipid
to-surfactant ratio (A, % w/w), Eudragit L100 (B, % w/w), and sonication time (C,
minutes) at three levels (-1 and +1 levels of quality central level) was applied
to develop SLNbp using response surface methodology at constant ratio of ISR and
rutin. The second-order polynomial quadratic equations of responses [R1, R2, and
R3; entrapment efficiency (EE), particle size, and drug release] were constructed
and also plotted response surface (two- and three-dimensional) plots. The derived
polynomial equation and 2D and 3D model were showed the relationship between the
responses of the selected independent variables (A, B, and C). The model
validation and optimization was performed by numerical checkpoint analysis to
predict the optimized solid lipid nanobioparticle formulas (ONbp 1-10). The
optimized formulations prepared and during evaluation ONbp 3 has better smaller
particle size (106 nm), sustainable release (95.61% up to 40 h), higher EE
(97.85%), and drug content (99.92% +/- 0.08%) during 3-month storage showed good
stability. Therefore, its performance can be considered for further development
of stable oral drug delivery system of ISR.
PMID- 29951292
TI - RETRACTION NOTE TO: Therapeutic benefits of phosphodiesterase-5 inhibition in
chronic heart failure: A meta-analysis.
AB - [This retracts the article DOI: 10.1556/1646.9.2017.26.].
PMID- 29951293
TI - Immunotherapy & thoracic cancers.
PMID- 29951294
TI - Is there a room for immune checkpoint inhibitors in early stage non-small cell
lung cancer?
AB - Early non-small cell lung cancer (NSCLC) represents 16% of all new NSCLC at
diagnosis with a 5-year survival rate of about 60%. Surgical intervention and
adjuvant platinum-based chemotherapy represent the cornerstone treatments, but no
significant advances have been achieved since several decades in term of relapse
rate reduction or survival improvement. Immunotherapy represents an appealing
strategy considering the acceptable toxicity profile but, despite the awesome
changing recently introduced in the locally advanced and metastatic setting, its
role in early NSCLC is not clear yet. In the past few years, two strategies have
been investigated to improve the early NSCLC outcomes eliciting the anti-tumour
immune response: tumour vaccines and adoptive cellular therapies. However, none
of them provided convincing results. Preclinical and clinical data supported the
prognostic role of immune checkpoints in resected NSCLC even if they did not show
a clear predictive value for adjuvant treatment. However, some preliminary data
about safety and efficacy of neo-adjuvant immune checkpoint inhibitors encourage
further investigation of their potential role as monotherapy or as part of a
multimodal strategy. Then, even if no significant progress has been done in early
NSCLC treatment until today, checkpoint inhibitors can open the door to a new
strategy in this setting.
PMID- 29951295
TI - The role of radiology in the evaluation of the immunotherapy efficacy.
AB - In the last years, a great interest has arisen on immunotherapy for the treatment
of advanced non-small cell lung cancer (NSCLC). Check-point inhibitor drugs are
now considered clinical practice standard in different settings and their use is
expected to increase significantly in the near future. As treatment options for
lung cancer advance and vary, the different patterns of radiological response
increase in number and heterogeneity. To correctly evaluate the radiological
findings after and during these treatments is of paramount importance, both in
the clinical and sperimental setting. In consideration of their peculiar
mechanism, immunotherapies can determine unusual response patterns on imaging,
that cannot be correctly evaluated with the traditional response criteria such as
World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumours
(RECIST). Therefore, during these years, several response criteria [immune
related response criteria (irRC), irRECIST and iRECIST] were proposed and applied
in clinical trials on immunotherapies. The aim of this review is to describe the
radiological findings after immunotherapy, to critically discuss the different
response criteria and the imaging of immune-related adverse events.
PMID- 29951296
TI - Combining immunotherapy and radiotherapy in lung cancer.
AB - Immunotherapy has become standard of care in advanced non-small cell lung cancer
(NSCLC) in a number of settings. Radiotherapy remains an important and
potentially curative treatment for localized and locally advanced NSCLC not
amenable to surgery. While the principal cytotoxic effect of ionizing radiation
is via DNA damage, the effect on tumour microenvironment, promoting dendritic
cell presentation of tumour-derived antigens to T cells stimulating the host
adaptive immune system to mount an immune response against tumours cells, has
become of particular interest when combining immunomodulating agents with
radiation. The 'abscopal effect' of radiation where non-irradiated metastatic
lesions may respond to radiation may be immune-mediated, via radiation primed
anti-tumour T cells. Immune priming by radiation offers the potential for
increasing the efficacy of immunotherapy and this is subject to on-going clinical
trials underpinned by immunological bioassays. Increasing understanding of the
interaction between tumour, radiation and immune cells at a molecular level
provides a further opportunity for intervention to enhance the potential synergy
between radiation and immunotherapy. Applying the potential efficacy of
combination therapy to clinical practice requires caution particularly to ensure
the safety of the two treatment modalities in early phase clinical trials, many
of which are currently underway. We review the biological basis for combining
radiation and immunotherapy and examine the existing pre-clinical and clinical
evidence and the challenges posed by the new combination of treatments.
PMID- 29951297
TI - Locally-advanced non-small cell lung cancer: shall immunotherapy be a new chance?
AB - Locally advanced non-small cell lung cancer (NSCLC) represents approximately one
third of presentations at diagnosis. Most patients are judged non-surgical due to
disease extension, and chemo-radiotherapy still represents the standard
therapeutic option, with unsatisfactory results in terms of overall survival (OS)
despite advances in staging and radiation therapy planning and delivery.
Immunotherapy, and in particular immune-checkpoint inhibitors targeting the PD
1/PD-L1 axis, gained wide popularity for NSCLC in light of the positive findings
of several trials in metastatic disease. Stage III unresectable NSCLC is a
remarkably interesting setting for the combined use of chemo-radiation and
immunotherapy, also considering the multiple experimental evidences in favor of a
synergistic effect between radiation and immune checkpoint inhibitors, with the
potential of enhancing immuno-modulating effects and overcoming resistance. We
here summarized the biological rationale and the initial clinical experiences
testing for this combination, and we briefly discussed ongoing trials and future
options in this field.
PMID- 29951298
TI - Advanced non-small cell lung cancer: the role of PD-L1 inhibitors.
AB - PD-L1 and PD-1 inhibitors were both developed to combat a huge array of cancers.
Both classes of agents block the PD-1/PD-L1 pathway. Unlike PD-1 inhibitors, PD
L1 inhibitors do also block the B-7.1-receptor and leave the PD-L2/PD-1 axis
unaffected. Whether these differences enhance efficacy and tolerability is not
clear yet. There are three PD-L1 inhibitors approved or in late clinical
development: Atezolizumab, approved in 2nd-line treatment of non-small cell lung
cancer, durvalumab, showing promising results as a consolidation therapy in stage
III disease and avelumab, the only drug exploiting antigen-dependent
cytotoxicity. Future directions are the combination of these compounds with
chemotherapy or other immuno-oncologic drugs.
PMID- 29951299
TI - Lung cancer, elderly and immune checkpoint inhibitors.
AB - Lung cancer is predominantly a disease of the elderly with about 50% of diagnoses
in patients aged >=70 years and about 14% in those older than 80. Medical and
physiological characteristics of elderly cancer patients make the choice of their
better treatment more challenging. Furthermore, aging is accompanied by the so
called "immunosenescence" phenomenon, the age-related decline in the immune
system that is one of the potential reasons of increase of the incidence and
prevalence of most cancers. There is a growing interest in understanding of
immunosenescence and how it may correlate with the use of immune checkpoint
inhibitors in elderly non-small cell lung cancer (NSCLC) patients. The survival
benefit achieved by immunotherapy in all histologies and therapy line settings,
added to its manageable toxicity profile, has dramatically changed the scenario
of advanced NSCLC treatment. At subgroup analyses of randomized clinical trials,
elderly NSCLC population seems to benefit from anti-programmed death-1 (anti-PD
1)/anti-programmed death ligand-1 (anti-PD-L1) agents' treatment. These efficacy
data were also confirmed by studies in real-life setting. The key-points of aging
and immunosenescence are described, focusing on the role of immune checkpoint
inhibitors in elderly NSCLC population.
PMID- 29951300
TI - Immunotherapy in the Asiatic population: any differences from Caucasian
population?
AB - As "Immunotherapy age" is coming, immune checkpoint inhibitors (CPI) therapies
have shown favorable clinical benefits and low toxicity profiles in patients with
advanced non-small cell lung cancer (NSCLC). While it is a pity that there is a
little clear clinical trials evidence about immunotherapy among Asian population.
Moreover, since there is an ethnic difference for targeted therapy, what about
immunotherapy? Which factors may associate with ethnic differences from Caucasian
population to Asiatic population? In this review, we supposed that the
characteristics of the much higher proportion of EGFR mutation, hepatitis B virus
infection and unexpected immune-related toxicity among Asian patients should be
considered.
PMID- 29951301
TI - Immune checkpoint blockade for advanced non-small cell lung cancer: challenging
clinical scenarios.
AB - Immune checkpoint blockade has shown anti-tumour activity and improved survival
in advanced non-small cell lung cancer (NSCLC). A number of anti-PD-1/PD-L1 and
CTLA-4 monoclonal antibody agents have been evaluated in metastatic non-small
cell lung cancer. Nivolumab, pembrolizumab and atezolizumab are currently
approved for use in clinical practice due to demonstrated improvement in response
rate, overall survival (OS) and quality of life (QoL) over standard chemotherapy.
We present a series of cases that highlight the clinical challenges that these
novel agents present. A review of rare immune-related adverse events (AEs),
optimal treatment duration and patient selection will be presented. This series
will also address real-life clinical scenarios such as treatment re-challenge and
management of immune-related AEs.
PMID- 29951302
TI - Thymic tumors and immune checkpoint inhibitors.
AB - Thymoma and thymic carcinoma, known as the most common features of thymic
epithelial tumors (TETs), are thoracic malignancies displaying varied clinical
features and prognosis. These neoplasms being frequently ineligible for surgical
complete resection as a curative treatment because of extensive tumor spread,
effectual nonsurgical treatments are needed; however, an optimal chemotherapeutic
regimen has not been identified, although some regimens have been shown to be
active. Immunotherapy is effective for other malignancies and may be promising as
a therapeutic alternative for refractory TETs. Thus far, several studies have
determined the expression of programmed death ligand 1 (PD-L1) and programmed
death 1 (PD-1) in TETs, including its clinicopathological and prognostic
significance. The results have been conflicting due to the different
immunohistochemical antibodies employed and distinct cutoff values. However, many
authors identified abundant PD-L1 expression in TETs, which is considered as an
important predictive factor for therapeutic effect of PD-1 inhibitors in other
malignant tumors. In some clinical trials, an acceptable clinical efficacy of PD
1 inhibitor for TETs has been reported as expected; however, concerns regarding
immunological adverse events have been raised. To optimize these therapeutic
agents for refractory TETs, additional studies which evaluate clinical
availabilities of immunotherapeutic drugs and characterize their basic mechanisms
of action against immunotherapeutic targets are both urgently required.
PMID- 29951303
TI - Immune-related adverse events with immune checkpoint inhibitors in thoracic
malignancies: focusing on non-small cell lung cancer patients.
AB - Immune checkpoint inhibitors (ICIs) have revolutionized treatment landscape among
non-small cell lung cancer (NSCLC) patients in first- and second-line setting,
and may become soon new treatment options in other thoracic malignancies such as
small cell lung cancer (SCLC) or mesothelioma. The use of these drugs has
indubitably changed the toxicity profile the oncologists are familiar with, and
new spectra of immune-related adverse events are being reported with the
widespread use of immunotherapies in solid tumors. Clinical management and
understanding of immune-related adverse events is new and complex but expertise
is still limited. In this review, we are summarizing the incidence and management
of main side effects related to ICIs focusing on NSCLC patients.
PMID- 29951304
TI - Shining light on advanced NSCLC in 2017: combining immune checkpoint inhibitors.
AB - The treatment landscape has changed since the immune checkpoint inhibitors were
approved in the treatment of non-small cell lung cancer (NSCLC). Although the
promising clinical benefit from programmed death-1/programmed death ligand-1 (PD
1/PD-L1) inhibitors was observed in the second or subsequent line treatment of
patients who progressed on chemotherapy, it has a long way for single PD-1/PD-L1
inhibitor to move forward to the frontline without a predictive biomarker. Tumor
response is far from satisfactory without selection and primary or acquired
resistance to PD-1/PD-L1 inhibitors hampered their utility. Therefore, it is
crucial to determine a strategy that can optimize the application of immune
checkpoint inhibitors and increase the numbers of the responders. Multiple
combination approaches based on PD-1/PD-L1 inhibitors are designed and aimed to
boost anti-tumor response and benefit a broader population. In this review, we
will integrate the updated clinical data to highlight the four most promising
combination strategies in advance NSCLC: combination of checkpoint inhibition
with chemotherapy, anti-angiogenesis, immunotherapy and radiotherapy. We further
discuss the issues needed to be addressed and perspectives in the context of
"combination era".
PMID- 29951305
TI - Oncogene-addicted non-small cell lung cancer and immunotherapy.
AB - A majority of non-small cell lung cancer (NSCLC), especially adenocarcinomas,
harbour at least one oncogenic driver mutation that can potentially be a target
for therapy. The treatment of these oncogene-addicted tumors has dramatically
changed the outcome of these patients, where tyrosine kinase inhibitors (TKIs) of
mutated epidermal growth factor receptor (EGFR) and rearranged anaplastic
lymphoma kinase (ALK) have paved the way for a new era of precision cancer
medicine. Another paradigm shift in the treatment of NSCLC, as well as numerous
other tumor types, has been the introduction of immunotherapy (IO) with immune
checkpoint inhibitors targeting mainly programmed cell death-1 (PD-1) or its
ligand PDL-L1, where studies have demonstrated an increased survival versus
standard treatment with chemotherapy, both in the first- and second-line setting.
However, the role of IO in oncogene-addicted NSCLC is still unclear where most
clinical data come from subgroup analyses with low number of patients in larger
randomized trials, and these data do not support the use of IO after TKI in this
category of NSCLC patients. The purpose of this review is to summarize the
existing evidence about the use of IO in oncogenic-addicted NSCLC and highlight
the issues that should be addressed in the future in order to define the role of
IO for these patients.
PMID- 29951306
TI - A review of guidelines for lung cancer.
AB - Clinical practice guidelines include recommendations intended to optimize patient
care. In the last years, the introduction of immune checkpoint inhibitors is
rapidly changing lung cancer management and therefore guidelines are essential to
assist clinicians in such an evolving field. We reviewed the recommendations
about the use of these immune checkpoint inhibitors in clinical practice
guidelines issued by three scientific societies [European Society of Medical
Oncology (ESMO); American Society of Clinical Oncology (ASCO); Italian
Association of Medical Oncology (AIOM)] and one not-for-profit U.S. alliance
[National Comprehensive Cancer Network (NCCN)] in order to underline their
strengths and limitations. All the examined guidelines include some
recommendations about use of immune checkpoint inhibitors in lung cancer
patients. ASCO guidelines have a good methodologic background while their major
limitation is their slow updating. NCCN guidelines, by contrast, are continuously
updated but suffer from weak methodology and poor comparative tools. ESMO
guidelines introduce a tool to assess the magnitude of clinical benefit for each
recommended intervention that, although with some limitations, may improve
clinical decision making. AIOM guidelines apply a robust methodology, but contain
recommendations only on drugs reimbursed in Italy, thus limiting their
applicability in different contexts. Clinical practice guidelines are useful
tools that assist clinicians treating lung cancer patients with immune checkpoint
inhibitors. Their use would improve homogeneity and appropriateness, even in this
rapidly evolving field.
PMID- 29951307
TI - Do immune checkpoint inhibitors need new studies methodology?
AB - Immune checkpoint inhibitors (ICI) have widely reshaped the treatment paradigm of
advanced cancer patients. Although multiple studies are currently evaluating
these drugs as monotherapies or in combination, the choice of the most accurate
statistical methods, endpoints and clinical trial designs to estimate the benefit
of ICI remains an unsolved methodological issue. Considering the unconventional
patterns of response or progression [i.e., pseudoprogression, hyperprogression
(HPD)] observed with ICI, the application in clinical trials of novel response
assessment tools (i.e., iRECIST) able to capture delayed benefit of
immunotherapies and/or to quantify tumor dynamics and kinetics over time is an
unmet clinical need. In addition, the proportional hazard model and the
conventional measures of survival [i.e., median overall or progression free
survival (PFS) and hazard ratios (HR)] might usually result inadequate in the
estimation of the long-term benefit observed with ICI. For this reason,
innovative methodologies such as milestone analysis, restricted mean survival
time (RMST), parametric models (i.e., Weibull distribution, weighted log rank
test), should be systematically investigated in clinical trials in order to
adequately quantify the fraction of patients who are "cured", represented by the
tails of the survival curves. Regarding predictive biomarkers, in particular PD
L1 expression, the integration and harmonization of the existing assays are
urgently needed to provide clinicians with reliable diagnostic tests and to
improve patient selection for immunotherapy. Finally, developing original and
high-quality study designs, such as adaptive or basket biomarker enriched
clinical trials, included in large collaborative platforms with multiple active
sites and cross-sector collaboration, represents the successful strategy to
optimally assess the benefit of ICI in the next future.
PMID- 29951310
TI - Keys to Achieving Target First Medical Contact to Balloon Times and Bypassing
Emergency Department More Important Than Distance.
AB - Background: Australian guidelines advocate primary percutaneous coronary
intervention (PPCI) as the reperfusion strategy of choice for ST elevation
myocardial infarction (STEMI) in patients in whom it can be performed within 90
minutes of first medical contact; otherwise, fibrinolytic therapy is preferred.
In a large health district, the reperfusion strategy is often chosen in the
prehospital setting. We sought to identify a distance from a PCI centre, which
made it unlikely first medical contact to balloon time (FMCTB) of less than 90
minutes could be achieved in the Hunter New England health district and to
identify causes of delay in patients who were triaged to a PPCI strategy. Methods
and Results: We studied 116 patients presenting via the ambulance service with
STEMI from January 2016 to December 2016. In patients who were taken directly to
the cardiac catheterisation lab, a maximum distance of 50 km from hospital
resulted in 75% of patients receiving PCI within 90 minutes and approximately 95%
of patients receiving PCI within 120 minutes. Patients who bypassed the emergency
department (ED) were significantly more likely to have FMCTB of less than 90
minutes (p < 0.001) despite having a longer travel distance (28.5 km versus 17.4
km, p < 0.001). Patients transiting via the ED were significantly more likely to
present out of hours (60 versus 24.2% p < 0.001). Conclusions: Patients who do
not bypass the ED have a longer FMCTB across all spectrum of distances from the
PCI centre; therefore, bypassing the ED is key to achieving target FMCTB times.
Using a cutoff distance of 50 km may reduce human error in estimating travel time
to our PCI centre and thereby identifying patients who should receive prehospital
thrombolysis.
PMID- 29951311
TI - Body Size Misperception and Overweight or Obesity among Saudi College-Aged
Females.
AB - The aim of the study was to investigate the associations between perceived and
desired body size and overweight and obesity among college-aged females. A
multistage stratified cluster random sample was used to select 907 healthy
females from a major Saudi public university. The Stunkard Figure Rating Scale
(FRS) was used for body size assessment. Overweight/obesity classification was
based on BMI less than or equal to/greater than 25 kg/m2. Overweight plus obesity
prevalence was 28.1%. There were significant differences between females with
overweight/obesity and those without overweight/obesity in both perceived and
desired body size scores. Compared with only 4% of females without
overweight/obesity, 37% of the participants with overweight/obesity scored higher
than five (median) in the FRS. The perceived body size correlated more strongly
with many of the selected variables than did the desired body size, especially
with BMI (r=0.679; p < 0.001), body weight (r=0.652; p < 0.001), and weight loss
attempts (r=0.466; p < 0.001). Also, there was a significant relationship between
BMI and weight loss attempts (r=0.370; p < 0.001). BMI and weight loss attempts
appear to predict the perceived body size and the discrepancy between perceived
and desired body size scores. Psychosocial and lifestyle factors that might
influence female's body misperception need to be addressed in future studies.
PMID- 29951309
TI - Vaccine and immune cell therapy in non-small cell lung cancer.
AB - Despite new advances in therapeutics, lung cancer remains the first cause of
mortality among different types of malignancies. To improve survival, different
strategies have been developed such as chemotherapy combinations, targeted
therapies and more recently immunotherapy. Immunotherapy is based on the
capability of the immune system to differentiate cancer cells from normal cells
to fight against the tumor. The two main checkpoint inhibitors that have been
widely studied in non-small cell lung cancer (NSCLC) are PD-1/PD-L1 and CTLA-4.
However, interactions between tumor and immune system are much more complex with
several different elements that take part and probably many new interactions to
be discovered and studied for a better comprehension of those pathways. Vaccines
are part of the prophylaxis and of the treatment for different infectious
diseases. For that reason, they have allowed us to improve global survival
worldwide. This same idea can be used for cancer treatment. First reports in
clinical trials that used therapeutic vaccines in NSCLC were discouraging, but
currently vaccines have a new chance in cancer therapy with the identification of
new targetable antigens, adjuvant treatments and most interestingly, the
combination of vaccines with anti-PD-1/PD-L1 and anti-CTLA-4 drugs. The aim of
this article is to describe the scientific evidence that has been reported for
the different types of vaccines and their mechanisms of action in the fight
against NSCLC tumors to improve disease control.
PMID- 29951312
TI - The Effect of Medium Chain Triglycerides on Time to Nutritional Ketosis and
Symptoms of Keto-Induction in Healthy Adults: A Randomised Controlled Clinical
Trial.
AB - Medium chain triglycerides (MCTs) are ketogenic and might reduce adverse effects
of keto-induction and improve time to ketosis and the tolerability of very low
carbohydrate diets. This study investigates whether MCT supplementation improves
time to nutritional ketosis (NK), mood, and symptoms of keto-induction. We
compared changes in beta-hydroxybutyrate (BOHB), blood glucose, symptoms of keto
induction, and mood disturbance, in 28 healthy adults prescribed a ketogenic
diet, randomised to receive either 30 ml of MCT, or sunflower oil as a control,
three times per day, for 20 days. The primary outcome measured was the
achievement of NK (>=0.5 mmol.L-1 BOHB). Participants also completed a daily
Profile of Mood States and keto-induction symptom questionnaire. MCT resulted in
higher BOHB at all time points and faster time to NK, a result that failed to
reach significance. Symptoms of keto-induction resulted from both diets, with a
greater magnitude in the control group, except for abdominal pain, which occurred
with greater frequency and severity in the MCT-supplemented diet. There was a
possibly beneficial effect on symptoms by MCT, but the effect on mood was
unclear. Based on these results, MCTs increase BOHB compared with LCT and reduce
symptoms of keto-induction. It is unclear whether MCTs significantly improve mood
or time to NK. The trial was registered by the Australia New Zealand Clinical
Trial Registry ACTRN12616001099415.
PMID- 29951308
TI - Next generation immune-checkpoints for cancer therapy.
AB - The discovery and clinical application of immune-checkpoint inhibitors has
dramatically improved the treatments, outcomes and therapeutic concepts in
multiple tumor settings. This breakthrough was mainly based on monoclonal
antibodies blocking the inhibitory molecule CTLA-4 and or the PD-1/PD-L1 axis,
with the aim of counteracting major tumor immune evasion mechanisms. Even
acknowledging these important successes, not all the patients benefit from these
treatments. Translational and clinical research efforts are ongoing to explore
the potentialities of a new generation of immune-modulatory molecules to extend
current clinical applications and contrast the unsolved issues of resistance and
disease relapse that still affects a considerable rate of patients. New immune
checkpoints, with either stimulatory or inhibitory functions are emerging with
key roles in regulating T cell response but also affecting other crucial
effectors belonging to the innate immune response (e.g., natural killer). Their
therapeutic exploitation, either alone or in strategical combinations, is
providing important preclinical results, holding promises currently explored in
initial clinical trials. The first results point toward favorable safety profiles
with selective hints of activity in challenging settings. Important issues
regarding the dose, schedule and rational combinations remain open and data from
the clinical studies are needed. Here we provide an overview of the main emerging
stimulatory or inhibitory immune-checkpoints exploitable in cancer treatment,
briefly reporting their biological function, preclinical activity and preliminary
clinical data.
PMID- 29951313
TI - The Prevalence of Depression among Diabetic Patients in Ethiopia: A Systematic
Review and Meta-Analysis, 2018.
AB - Background: Diabetes mellitus is a chronic metabolic disorder characterized by
hyperglycemia. Depression is one of the major important public health problems
that is often comorbid with diabetes. Despite the huge effect of comorbid
depression and diabetes, the overall pooled prevalence of depression among
diabetic patients in the country level remains unknown. Therefore, the objective
of this systematic review and meta-analysis is to estimate the pooled prevalence
of depression among patients with diabetes mellitus in Ethiopia. Method: Data
extraction was designed in accordance with the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were accessed
through electronic web-based search from PubMed, Cochrane Library, Google
Scholar, Embase, and PsycINFO. All statistical analyses were done using STATA
version 11 software using random effects model. The pooled prevalence was
presented in forest plots. Results: A total of 9 studies with 2944 participants
were included in this meta-analysis and the overall pooled estimated prevalence
of depression among diabetic patients in Ethiopia was 39.73% (95% CI (28.02%,
51.45%)). According to subgroup analysis the estimated prevalence of depression
in Addis Ababa was 52.9% (95% CI: 36.93%, 68.88%) and in Oromia region was 45.49%
(95% CI: 41.94, 49.03%). Conclusion: The analysis revealed that the overall
prevalence of comorbid depression among diabetic patients in Ethiopia was high.
Therefore, Ministry of Health should design multisectorial approach and context
specific interventions that address this comorbid depression in this specific
group as well as general population.
PMID- 29951314
TI - Effect of the PIVO Device on the Procedure of Phlebotomy from Peripheral IV
Catheters.
AB - Short peripheral catheters (SPC) are an existing conduit into many patients'
veins and line draws from SPC are a desired method of routine blood collection
especially in difficult venous access patients. The PIVO device facilitates blood
collection through SPC and is being used clinically in a number of hospitals.
This study aimed to determine the appropriate wait time following a flush and the
minimum waste volume required to obtain an undiluted blood sample when using the
PIVO device and how that differed from current guidelines from SPC line draws. A
clinical study was conducted examining the analyte results of samples drawn with
PIVO through a SPC at varying wait times following a saline flush. Both an
initial waste volume and a postwaste sample were compared to a venipuncture
control. The resulting samples showed no saline dilution as measured by sodium
and creatinine results at all studied wait times. These findings suggest that
blood collections using the PIVO device can produce a clinically valid sample
with a 30-second wait following a SPC flush and no waste volume prior to sample
collection.
PMID- 29951315
TI - Molecular Mechanisms Underlying Accelerated Aging by Defects in the FGF23-Klotho
System.
AB - The basic research of aging has been primarily focused on elucidating mechanisms
of aging and longevity that are evolutionarily conserved from yeasts to primates.
Such efforts have culminated in the notion that (1) senescence at the cellular
level is associated with aging at the organismal level and that (2) calorie
restriction and growth suppression decelerate aging. However, these important
findings in the basic research have not necessarily been linked to improvement of
daily medical practice in the aging society. It has become increasingly important
to investigate mechanisms of aging unique to mammals or humans and apply the
research fruits for the treatment of major age-related disorders to extend the
health span. Seminal studies on the klotho mouse, a mutant exhibiting a premature
aging syndrome, have identified phosphate as a proaging factor in mammals. In
this review, mechanisms of phosphate-induced premature aging and potential
therapeutic targets will be discussed, which may be directly applicable for
developing novel strategies for the treatment of chronic kidney disease and its
complications.
PMID- 29951316
TI - Emphasized Mechanistic Antimicrobial Study of Biofunctionalized Silver
Nanoparticles on Model Proteus mirabilis.
AB - Antimicrobial study of biofunctionalized silver nanoparticles has been done with
the emphasis on its mechanism on both gram positive and negative bacteria. The
biofunctionalized silver nanoparticles are employed considering their importance
in green chemistry with respect to easy synthesis, usefulness, and economic
synthetic procedure involved. The stability of these nanoparticles was determined
by zeta potential analyzer. The probable mechanism of antibacterial activity was
performed on Proteus mirabilis by field emission scanning electron microscopy
(FESEM) and energy dispersive spectroscopy (EDAX) study which does not show the
presence of silver. The free radicals generated by silver nanoparticles were
responsible for lethal antibacterial activity by rupturing the cell surface which
causes improper nutrient and signal supply. Free radical scavenging efficacy of
silver nanoparticles was confirmed by 1,1-Diphenyl-2-picrylhydrazyl (DPPH)
method. AgNP enhanced the membrane leakage of reducing sugars by destroying the
proteins existing on the cell wall. These nanoparticles are found to be toxic
against human pathogens and are highly effective on Staphylococcus aureus. The
effect of silver nanoparticles is concentration dependent and independent of the
type of strains used.
PMID- 29951317
TI - Differential Regulation of Escherichia coli fim Genes following Binding to
Mannose Receptors.
AB - Regulation of the uropathogenic Escherichia coli (UPEC) fimB and fimE genes was
examined following type 1 pili binding to mannose-coated Sepharose beads. Within
25 min after mannose attachment, fimE expression dropped eightfold, whereas fimB
transcription increased about two- to fourfold. Because both fim genes encode
site-specific recombinases that affect the position of the fimS element
containing the fimA promoter, the positioning of fimS was also examined. The fimS
element changed to slightly more Phase-OFF in bacteria mixed with plain beads,
whereas UPEC cells interacting with mannose-coated beads had significantly less
Phase-OFF orientation of fimS under pH 7 conditions. On the other hand, Phase-OFF
oriented fimS increased fourfold when UPEC cells were mixed with plain beads in a
pH 5.5 environment. Positioning of fimS was also affected by fimH mutations,
demonstrating that the FimH ligand binding to its receptor facilitates the
changes. Moreover, enzyme immunoassays showed that UPEC cells had greater type 1
pili expression when mixed with mannose-coated beads versus plain beads. These
results indicate that, after type 1 pilus binding to tethered mannose receptors,
the physiology of the E. coli cells changes to maintain the expression of type 1
pili even when awash in an acidic environment.
PMID- 29951319
TI - Closed Reduction in a "Hyperextended Supine Position" with Percutaneous
Transsacral-Transiliac and Iliosacral Screw Fixation for Denis Zone III Sacral
Fractures.
AB - Background: Herein, we demonstrate the clinical results of closed reduction in a
hyperextended supine position with transsacral-transiliac (TSTI) and iliosacral
(IS) screw fixations for Denis zone III sacral fractures. Patients and Methods:
Sixteen consecutive patients with Denis zone III sacral fractures who were
treated between January 2009 and September 2016 were evaluated. All patients were
treated using percutaneous TSTI/IS screw fixation during closed reduction
performed with patients placed in a hyperextended supine position with body
manipulation. The clinical and radiological results were evaluated, and the
neurological outcomes were retrospectively assessed using Gibbon's classification
system. The clinical outcomes were evaluated using the German Multicenter Study
Group Pelvic Outcome Scale (POS). Results: The sacral kyphotic angle was reduced
by 18.06 degrees +/- 15.26 degrees (mean kyphotic angle: pre-OP, 39.44 degrees
+/- 20.56 degrees ; post-OP, 21.38 degrees +/- 7.39 degrees ), and fracture
translation was reduced by 5.93 +/- 4.95 mm (mean fracture translation: pre-OP,
8.69 +/- 8.03 mm; post-OP 2.75 +/- 3.97 mm). The mean initial Gibbon's score was
3.00 +/- 1.32. Among 15 patients with a follow-up duration of over 12 months, the
mean reduction loss in the sacral kyphotic angle was 5.87 degrees +/- 10.40
degrees and was 1.00 +/- 3.00 mm for the fracture translation. The final
Gibbon's score was 1.80 +/- 1.21, and 73.3% of patients had good results based on
the POS score. Conclusions: Although closed reduction in a hyperextended supine
position with percutaneous posterior screw fixation is associated with some
surgical limitations and technical difficulties, the procedure is minimally
invasive and highly effective for stabilizing Denis zone III sacral fractures.
PMID- 29951318
TI - Diagnosis of Helicobacter pylori Using Invasive and Noninvasive Approaches.
AB - Helicobacter pylori (H. pylori) as gram-negative and spiral microorganism is
responsible for colonization in the gastric microniche for more than 50% of world
population. Recent studies have shown a critical role of H. pylori in the
development of peptic ulcers, gastric mucosa-associated lymphoid tissue (MALT)
lymphoma, and gastric cancer. Over the past decade, there has been a sharp
interest to use noninvasive tests in diagnosis of the H. pylori infection. During
the years after discovery by Marshall and Warren, it has been frequently declared
that the rapid urease test (RUT) is one of the cheapest and rapid diagnostic
approaches used in detecting the infection. Although the specificity and
sensitivity are durable for this test, clinical experiences had shown that the
ideal results are only achieved only if we take biopsies from both corpus and
antrum at the same time. Given the diagnosis of the H. pylori in clinical
samples, gastroenterologists are facing a long list of various molecular and
nonmolecular tests. We need more in-depth researches and investigations to
correctly generalize rapid and accurate molecular tests determining both
bacterial identity and antibiotic resistance profile.
PMID- 29951320
TI - Allograft Reconstruction of the Extensor Mechanism after Resection of Soft Tissue
Sarcoma.
AB - Introduction: Soft tissue tumors around the knee joint still pose problems for
the excision and subsequent reconstruction. Methods: In the 6 included patients
the soft tissue sarcoma has its base on the anterior surface of the extensor
mechanism and expands towards the skin. The entire extensor apparatus (quadriceps
tendon, patella, and patellar tendon) was resected and replaced by a fresh-frozen
allograft. Results: The mean follow-up was 6.7 years (range: 2-12.4 years). In
two patients a local recurrence occurred, resulting in a 5-year local recurrence
free rate of 66.7% (95% CI: 19.5%-90.4%). Distant metastases were found in 4
patients resulting in a 5-year metastasis-free rate of 33.3% (95% CI: 4.6%
67.5%). Two patients underwent at least one revision surgery, including one
patient in whom the allograft had to be removed. According to the ISOLS function
score 24.7 points (range: 19-28 points) were achieved at the last follow-up. The
mean active flexion of the knee joint was 82.5 degrees (range: 25-120 degrees )
and a mean extension lag of 10 degrees (range: 0-30 degrees ) was observed.
Conclusions: The replacement of the extensor mechanism by an allograft is a
reasonable option, allowing wide margins and restoration of active extension in
most patients. Trial Registration: The presented study is listed on the ISRCTN
registry with trial number ISRCTN63060594.
PMID- 29951321
TI - Management of a Parturient with Mast Cell Activation Syndrome: An
Anesthesiologist's Experience.
AB - Mast cell activation syndrome (MCAS) is a disorder in which patients experience
symptoms and signs attributable to inappropriate mast cell activation and
mediator release. Multiorgan involvement in patients can result in significant
morbidity and possible mortality. Limited literature exists regarding anesthetic
management of patients with MCAS. We report a case of vaginal delivery with
neuraxial labor analgesia in a parturient with this condition and highlight the
importance of multidisciplinary planning for uneventful outcomes. Stress can
trigger life-threatening symptoms, and counseling is important to allay patients'
fears. Optimum medical control, adequate premedication, avoidance of triggers,
and preparedness to treat serious mediator effects are key. We review MCAS and
discuss anesthetic considerations for patients with this mast cell disorder.
PMID- 29951322
TI - Staphylococcus aureus Myocarditis with Associated Left Ventricular Apical
Thrombus.
AB - Staphylococcus aureus myocarditis is a rare diagnosis with a high mortality rate,
usually seen in people who are immunocompromised. Here, we report a case of a 44
year-old man on methotrexate for rheumatoid arthritis who presented in septic
shock and was diagnosed with staphylococcus aureus myocarditis. The myocarditis
was associated with a left ventricular apical thrombus, with normal systolic
function. The myocarditis and associated thrombus were characterised on
transthoracic echocardiogram and subsequently on cardiac magnetic resonance
imaging. Cardiac magnetic resonance (CMR) imaging showed oedema in the
endomyocardium, consistent with acute myocarditis, associated with an apical
mural thrombus. Repeat CMR 3 weeks following discharge from hospital showed
marked improvement in endomyocardial oedema and complete resolution of the apical
mural thrombus. He was treated with a 12-week course of antibiotics and
anticoagulated with apixaban. The patient was successfully managed with
intravenous antibiotics and anticoagulation with complete recovery.
PMID- 29951323
TI - The Heart as a Site of Metastasis of Benign Metastasizing Leiomyoma: Case Report
and Review of the Literature.
AB - Uterine leiomyomas are the most common gynecological tumors in premenopausal
women. While the lung is the most common extrauterine organ afflicted, benign
metastasizing leiomyomas (BML) of the heart are rarities. We report an incidental
finding of a cardiac mass in a 36-year-old woman who presented to the Emergency
Department after a motor vehicle accident. CT scan of the chest revealed 2 well
circumscribed pulmonary nodules and a filling defect in the right ventricle.
Echocardiogram showed a 4 cm mass attached to the right ventricular (RV) septum.
The cardiac tumor was resected and showed benign histologic features.
Immunohistochemical staining was positive for smooth muscle alpha-actin and
desmin, as well as estrogen and progesterone receptors, consistent with the
diagnosis of uterine leiomyoma.
PMID- 29951324
TI - Transcatheter Coil Embolization of Single Coronary Artery Fistula Using the
Occlusion Test.
AB - The case of a patient in whom hemodynamic and electrocardiographic studies using
the occlusion test for coronary artery fistulas (CAF) were safely performed prior
to catheter embolization is reported. A 1-year-old girl had a separate right
coronary artery arising from a left single coronary artery that formed a
significant coronary artery fistula to the right ventricle. Coronary steal by the
large coronary artery fistula narrowed the left coronary artery. The right
coronary artery branches could not be clearly identified due to an overlap with
the fistula. Due to the long porous CAF, embolic procedures could cause serious
complications. We confirmed the safety by performing an occlusion test of the
CAF's proximal blood vessels. Following total occlusion of the CAF for 10
minutes, pulmonary arterial pressure and aortic blood pressure were not
significantly changed. No bradycardia, atrioventricular block, or ST changes were
observed. Coil embolization treatment was performed safely. For patients with
long distal CAF complicated with a single coronary artery, myocardial ischemia
and conduction system disorders can be identified by performing the occlusion
test before embolization.
PMID- 29951325
TI - Bisoprolol Transdermal Patch Is Effective for the Treatment of AF Tachycardia.
AB - Atrial fibrillation (AF) is an irregular and often rapid heart rate that can
increase the risk of stroke, heart failure, and other heart-related
complications. Its incidence increases with age and the presence of concomitant
heart disease. We present the cases of a 93-year-old woman, an 82-year-old man,
and an 87-year-old woman who developed AF tachycardia. This report highlights the
use of a bisoprolol transdermal patch to treat AF tachycardia in 3 adult elderly
patients. In this paper, we report an initial treatment strategy using a
bisoprolol transdermal patch and show heart rate trends for 24 hours.
PMID- 29951326
TI - The Risk of Immunosuppression: A Case of Salmonella Meningitis.
AB - Salmonella meningitis is a rare infection, particularly in adults. We report the
case of a 75-year-old female with a history of rheumatoid arthritis on TNF
antagonist immunosuppressive therapy who initially presented to the hospital for
management of back and leg pain and was ultimately diagnosed with bacterial
meningitis secondary to Salmonella species infection. She was treated with
ceftriaxone with slow improvement in neurological function. Though the source of
infection was never clearly identified from multiple imaging studies, we suspect
the severity of her presentation was due to her history of TNF-antagonist use.
PMID- 29951327
TI - A Case of Pelvic Abscess Caused by Edwardsiella tarda followed by Laparoscopic
Resection of a Hematoma Derived from Caesarean Section.
AB - Edwardsiella tarda (E. tarda) infections are rare and can be fatal. We report a
case of an E. tarda abscess which developed in the hematoma originally derived
from a caesarean section. A 24-year-old gravida 1 woman was admitted to our
hospital with a complaint of abdominal pain. Approximately one month before her
admission, pelvic hematoma had developed derived from caesarean section. Followed
by the failure of conservative management, she underwent laparoscopic surgery to
remove the hematoma 6 days before her admission. On computed tomography
examination, we found that the abscess with a diameter of 9 cm was located in the
right pelvic space. We punctured the abscess and identified E. tarda in the
abscess. We continued administering antibiotics, but her symptoms, including
fever and abdominal pain, became worse, and the abscess enlarged. We performed
laparotomy drainage and ileocecal resection on the 10th posthospitalization day.
After drainage surgery, the patient's condition improved gradually, and the
patient was discharged uneventfully. There are no reports in patients of E. tarda
infection during the perinatal period. E. tarda infection can be a life
threatening illness even in immunocompetent patients. In the case of E. tarda
infection, intensive care and surgical procedures should be considered.
PMID- 29951328
TI - Clostridium subterminale Septicemia in a Patient with Metastatic Gastrointestinal
Adenocarcinoma.
AB - Clostridium subterminale is a rare member of the Clostridiaceae family that is
rarely cultured. This report examines a case of Clostridium subterminale cultured
from the blood of a 72-year-old man who was ultimately diagnosed with metastatic
gastrointestinal (GI) adenocarcinoma. The patient was receiving treatment for
nosocomial pneumonia prior to culture of the C. subterminale, which led to
suspicion for malignancy. Extensive GI and oncologic workup demonstrated multiple
comorbidities and a primary GI cancer, which likely caused a breach in the GI
mucosa and C. subterminale entrance into the bloodstream. After a prolonged
intensive care unit (ICU) stay, the patient died on hospital day 23. Though
rarely reported, C. subterminale septicemia has been demonstrated in patients
with malignancy, specifically of the GI tract. Therefore, this case represents a
typical C. subterminale septicemia patient. Given the prevalence of Clostridia
and the contemporary emergence of multidrug resistant (MDR) microorganisms, both
typical and atypical cases regarding rare members of the species have a
significant role in the clinical management and public health planning.
PMID- 29951329
TI - Internal Auditory Canal Dural Enhancement in Granulomatosis with Polyangeitis
Disease.
AB - Diffuse dural enhancement of the internal auditory canal in T1-weighted
gadolinium-enhanced magnetic resonance imaging could be a helpful and early
clinical sign in a very aggressive limited granulomatosis with polyangeitis
disease, called previously Wegener Disease (WD).
PMID- 29951330
TI - Vasogenic Cerebral Edema following CT Myelogram with Nonionic Omnipaque 300.
AB - Computed Tomography (CT) with myelogram is a relatively safe procedure. It
requires the use of nonionic contrast agents which, unlike ionic contrast agents,
have been associated with low complication rates. We report a case of a 69-year
old female who developed diffuse bilateral cerebral edema following a lumber
myelogram with the use of intrathecal nonionic contrast agent Omnipaque (Iohexol)
300. We were able to find one other reported case of cerebral edema following the
use of intrathecal nonionic contrast agent in the literature.
PMID- 29951331
TI - Nonspecific Symptoms in a Rare Case of Urethral Adenocarcinoma in a 58-Year-Old
Female.
AB - Cancer of the urethra is very rare with an age-adjusted incidence of only 0.6 per
million women in Europe. The etiology is multifactorial and the incidence
increases with age, with the highest rates in patients 75 years or older. We
herein describe a 58-year-old woman referred to our unit due to pollakisuria and
repeated lower urinary tract infections. The gynecological examination revealed a
suspect area in the anterior wall of vagina. Subsequently, ultrasound
examination, MRI, and PET-CT scan followed by vaginal biopsies revealed a
urethral adenocarcinoma.
PMID- 29951332
TI - Case Report of an Acute Complex Perilunate Fracture Dislocation Treated with a
Three-Corner Fusion.
AB - Perilunate fracture dislocations are a rare but devastating injury, which is
often missed on initial presentation leading to significant delays in treatment.
With the delay in treatment and a high energy mechanism of injury, patients are
at increased risk of developing complex regional pain syndrome following trauma.
In this report, we review the case of a 57-year-old left-hand dominant female who
presented to a clinic with a five-and-a-half-week-old transtriquetral, perilunate
fracture dislocation with comminution of the scaphoid facet. Due to the increased
likelihood of a secondary procedure and low probability of a satisfactory outcome
with open reduction internal fixation secondary to the loss of the scaphoid
articulation, a salvage procedure was deemed her best option. To our knowledge,
this is the first case reported in the literature in which a scaphoidectomy,
triquetromy, and midcarpal fusion (three-corner fusion) was performed in the
acute setting for a perilunate fracture dislocation.
PMID- 29951333
TI - A Chronic Glottic Foreign Body Diagnosed by Radiograph after 9 Months of
Symptoms.
AB - A six-year-old girl presented to an emergency room after describing choking on a
rubber band. She was in no distress and was discharged. Over the course of the
next 9 months, she had numerous outpatient and emergency room visits due to
intermittent stridor, difficulty breathing, and hoarseness. Eventually, dedicated
airway films revealed a laryngeal foreign body. During rigid bronchoscopy, a two
centimeter rubber band was discovered in the larynx. It extended from the
supraglottis, through the glottis, and into the subglottis. It was successfully
removed. The patient was asymptomatic 24 hours later. This case highlights the
appropriate evaluation and management of a child with stridor.
PMID- 29951334
TI - Imaging and Histopathologic Nuances of Epithelioid Glioblastoma.
AB - A 27-year-old male without significant past medical history presented following
collapse resulting from a syncopal episode at work. There was an episode of
vomiting, and one of tonic-clonic seizure activity, which was spontaneously
resolved after approximately one minute. His neurologic exam was nonfocal, with
full strength in the bilateral upper and lower extremities, and no sensory
deficits were elicited. MRI studies demonstrated a 4.7 cm rim-enhancing cystic
mass in the right temporal-parietal region, with resultant mass effect and edema.
At surgery, intraoperative pathologic consultation favoured a primary glial
neoplasm. Subsequent complete histologic examination on permanent sections
confirmed the presence of glioblastoma, with a morphologic pattern and
immunohistochemical profile most consistent with epithelioid glioblastoma (WHO
grade IV). Epithelioid glioblastoma is a rare, especially aggressive variant of
IDH-wildtype glioblastoma, recognized in the 2016 World Health Organization
classification. Approximately 50% of such tumors harbour the BRAF V600E mutation,
which has also been observed in some melanomas where selective inhibitors have
demonstrated a therapeutic role. The especially aggressive behaviour and poor
clinical outcome typically observed for this variant of glioblastoma demonstrate
the importance of emerging areas relevant to neurooncology, specifically those of
proteomic characterization and therapeutic nanomedicine.
PMID- 29951335
TI - Key questions about the checkpoint blockade-are microRNAs an answer?
AB - The introduction of immune-checkpoint blockade in the cancer therapy led to a
paradigm change of the management of late stage cancers. There are already
multiple FDA approved checkpoint inhibitors and many other agents are undergoing
phase 2 and early phase 3 clinical trials. The therapeutic indication of immune
checkpoint inhibitors expanded in the last years, but still remains unclear who
can benefit. MicroRNAs are small RNAs with no coding potential. By complementary
pairing to the 3' untranslated region of messenger RNA, microRNAs exert
posttranscriptional control of protein expression. A network of microRNAs
directly and indirectly controls the expression of checkpoint receptors and
several microRNAs can target multiple checkpoint molecules, mimicking the
therapeutic effect of a combined immune checkpoint blockade. In this review, we
will describe the microRNAs that control the expression of immune checkpoints and
we will present four specific issues of the immune checkpoint therapy in cancer:
(1) imprecise therapeutic indication, (2) difficult response evaluation, (3)
numerous immunologic adverse-events, and (4) the absence of response to immune
therapy. Finally, we propose microRNAs as possible solutions for these pitfalls.
We consider that in the near future microRNAs could become important therapeutic
partners of the immune checkpoint therapy.
PMID- 29951336
TI - PD-1/PD-L1 pathway blockade works as an effective and practical therapy for
cancer immunotherapy.
AB - Cancer immunotherapy has greatly advanced in recent years, and PD-1/PD-L1
blocking therapy has become a major pillar of immunotherapy. Successful clinical
trials of PD-1/PD-L1 blocking therapies in cancer treatments have benefited many
patients, which promoted the Food and Drug Administration (FDA) approval of PD
1/PD-L1 blocking drugs. In this review, we provide a detailed introduction of
five PD-1/PD-L1 blocking drugs, with indications and studies, as a valuable
reference for doctors and medical investigators. Moreover, the characteristics of
PD-1/PD-L1 blocking therapies, including their universality and sustainability,
are discussed in this review. Furthermore, we also discuss and predict the
possibility of PD-L1 as an indication marker of PD-1/PD-L1 blocking therapy for
pan-cancer treatment, and the current status of combination therapies.
PMID- 29951337
TI - Progress in non-invasive detection of liver fibrosis.
AB - Liver fibrosis is an important pathological precondition for hepatocellular
carcinoma. The degree of hepatic fibrosis is positively correlated with liver
cancer. Liver fibrosis is a series of pathological and physiological process
related to liver cell necrosis and degeneration after chronic liver injury, which
finally leads to extracellular matrix and collagen deposition. The early
detection and precise staging of fibrosis and cirrhosis are very important for
early diagnosis and timely initiation of appropriate therapeutic regimens. The
risk of severe liver fibrosis finally progressing to liver carcinoma is >50%. It
is known that biopsy is the gold standard for the diagnosis and staging of liver
fibrosis. However, this method has some limitations, such as the potential for
pain, sampling variability, and low patient acceptance. Furthermore, the
necessity of obtaining a tissue diagnosis of liver fibrosis still remains
controversial. An increasing number of reliable non-invasive approaches are now
available that are widely applied in clinical practice, mostly in cases of viral
hepatitis, resulting in a significantly decreased need for liver biopsy. In fact,
the non-invasive detection and evaluation of liver cirrhosis now has good
accuracy due to current serum markers, ultrasound imaging, and magnetic resonance
imaging quantification techniques. A prominent advantage of the non-invasive
detection and assessment of liver fibrosis is that liver fibrosis can be
monitored repeatedly and easily in the same patient. Serum biomarkers have the
advantages of high applicability (>95%) and good reproducibility. However, their
results can be influenced by different patient conditions because none of these
markers are liver-specific. The most promising techniques appear to be transient
elastography and magnetic resonance elastography because they provide reliable
results for the detection of fibrosis in the advanced stages, and future
developments promise to increase the reliability and accuracy of the staging of
hepatic fibrosis. This article aims to describe the recent progress in the
development of non-invasive assessment methods for the staging of liver fibrosis,
with a special emphasize on computer-aided quantitative and deep learning
methods.
PMID- 29951338
TI - Enterolactone modulates the ERK/NF-kappaB/Snail signaling pathway in triple
negative breast cancer cell line MDA-MB-231 to revert the TGF-beta-induced
epithelial-mesenchymal transition.
AB - Objective: Triple-negative breast cancer (TNBC) is highly metastatic, and there
is an urgent unmet need to develop novel therapeutic strategies leading to the
new drug discoveries against metastasis. The transforming growth factor-beta (TGF
beta) is known to promote the invasive and migratory potential of breast cancer
cells through induction of epithelial-mesenchymal transition (EMT) via the ERK/NF
kappaB/Snail signaling pathway, leading to breast cancer metastasis. Targeting
this pathway to revert the EMT would be an attractive, novel therapeutic strategy
to halt breast cancer metastasis. Methods: Effects of enterolactone (EL) on the
cell cycle and apoptosis were investigated using flow cytometry and a cleaved
caspase-3 enzyme-linked immunosorbent assay (ELISA), respectively. Effects of TGF
beta induction and EL treatment on the functional malignancy of MDA-MB-231 breast
cancer cells were investigated using migration and chemo-invasion assays. The
effects of EL on EMT markers and the ERK/NF-kappaB/Snail signaling pathway after
TGF-beta induction were studied using confocal microscopy, quantitative reverse
transcription polymerase chain reaction (qRT-PCR), Western blot, and flow
cytometry. Results: Herein, we report that EL exhibits a significant
antimetastatic effect on MDA-MB-231 cells by almost reverting the TGF-beta
induced EMT in vitro. EL downregulates the mesenchymal markers N-cadherin and
vimentin, and upregulates the epithelial markers E-cadherin and occludin. It
represses actin stress fiber formation via inhibition of mitogen-activated
protein kinase p-38 (MAPK-p38) and cluster of differentiation 44 (CD44). EL also
suppresses ERK-1/2, NF-kappaB, and Snail at the mRNA and protein levels.
Conclusions: Briefly, EL was found to inhibit TGF-beta-induced EMT by blocking
the ERK/NF-kappaB/Snail signaling pathway, which is a promising target for breast
cancer metastasis therapy.
PMID- 29951339
TI - Clinical significance of miRNA - 106a in non-small cell lung cancer patients who
received cisplatin combined with gemcitabine chemotherapy.
AB - Objective: Research has demonstrated that microRNA (miR)-106a is related to
cisplatin resistance. We investigated the expression of miR-106a in the serum of
patients with non-small cell lung cancer (NSCLC) and their sensitivity to
chemotherapy by cisplatin combined with gemcitabine. Methods: Eighty-five NSCLC
patients, who completed four cycles of gemcitabine and cisplatin chemotherapy,
volunteered for this study and their serum samples were collected. Serum samples
from 60 healthy subjects were used as controls. Real-time quantitative polymerase
chain reaction (real-time qPCR) was used to quantify the level of miR-106a in the
serum. Demographic and survival data of these patients were collected for the
analysis. Results: The expression of miR-106a in the serum of NSCLC patients was
significantly higher than that of healthy subjects (P < 0.001). The expression of
miR-106a was not correlated with patients' gender, age, tumor size, lymphatic
metastasis, and pathological types; but was correlated with patients' tumor
staging ( P = 0.003). After chemotherapy, serum miR-106a expression decreased in
patients. The decrease in miR-106a expression in the chemotherapy-sensitive group
was much higher than that in the chemotherapy-resistant group. Survival analysis
shows that NSCLC patients with high expression of miR-106a have a poorer
prognosis. The overall survival of NSCLC patients in the chemotherapy-sensitive
group was significantly higher than that in the chemotherapy-resistant group.
Conclusions: High expression of miR-106a may be involved in the development of
NSCLC. MiR-106a has significance in the prognosis of NSCLC. The level of miR-106a
in the serum can be a useful parameter in screening for drug resistance during
cisplatin-based chemotherapy.
PMID- 29951340
TI - Diagnostic value of whole-body MRI with diffusion-weighted sequence for detection
of peritoneal metastases in colorectal malignancy.
AB - Objective: To assess the diagnostic accuracy of whole-body MRI using diffusion
weighted sequence (WB-DWI) to determine the peritoneal cancer index (PCI) in
correlation with surgical and histopathological findings. Methods: Twenty-seven
patients underwent preoperative WB-MRI, followed by cytoreductive surgery for
primary tumors of the appendix (n = 15), colorectum (n = 12), and associated
peritoneal disease. A total of 351 regions were retrospectively reviewed. The
sensitivity, specificity, and accuracy were calculated at 13 anatomical sites.
The WB-DWI PCI and PCI type were compared with surgical and histopathological
findings. Results: No statistical difference was found between the WB-DWI PCI and
surgical PCI (P = 0.574). WB-DWI correctly predicted the PCI type in 24 of 27
patients with high accuracy (88.9%), including 10 of 10 patients with small
volume tumor, 12 of 14 with moderate-volume tumor, and 2 of 3 with large-volume
tumor. WB-DWI correctly depicted tumors in 163 of 203 regions, with 40 false
negative and 23 false-positive regions. The overall sensitivity, specificity, and
accuracy of WB-DWI for the detection of peritoneal tumors were 80.3%, 84.5%, and
82.1%, respectively. For lesions < 0.5 cm in diameter, WB-DWI demonstrated good
sensitivity (69.4%). Conclusions: WB-DWI accurately predicted PCI before surgery
in patients undergoing evaluation for cytoreductive surgery.
PMID- 29951341
TI - Ultrasound features of extranodal extension in the metastatic cervical lymph
nodes of papillary thyroid cancer: a case-control study.
AB - Objective: Extranodal extension in cervical lymph nodes is an important risk
factor for the progression and prognosis of papillary thyroid cancer. The purpose
of this study was to identify the common and characteristic preoperative
ultrasonography features that are associated with the pathologic extranodal
extension of metastatic papillary thyroid carcinoma. Methods: We retrospectively
assessed and compared clinicopathologic and ultrasound features between 60
papillary thyroid cancer patients with extranodal extension and 120 control
patients with papillary thyroid cancer without extranodal extension. Results:
With respect to the pathological N stage and clinicopathologic features, N1b
stage papillary thyroid carcinomas were more frequently found in patients who
were extranodal extension-positive, in comparison with those who were extranodal
extension-negative (78.3% vs. 63.3%, P=0.043). Extranodal extension was detected
most frequently in level VI cervical lymph nodes (48.7%). In our univariate
analysis of patients with papillary thyroid carcinoma, cervical lymph nodes with
extranodal extension showed higher incidences of node matting,
microcalcification, cystic area, aspect ratio <2, and larger diameter than those
without extranodal extension (all P<0.05). Our multivariate analysis demonstrated
that node matting and cystic area were independent risk factors for the presence
of extranodal extension [odds ratio (OR): 4.751, 95% confidence interval (CI):
1.212~18.626, P=0.025; OR: 2.707, 95% CI: 1.127~6.502, P=0.026]. Conclusions:
Common ultrasound features may indicate the presence of extranodal extension in
patients with metastatic cervical lymph nodes of papillary thyroid carcinoma.
PMID- 29951342
TI - Primary resistance to crizotinib treatment in a non-small cell lung cancer
patient with an EML4-ALK rearrangement: a case report.
AB - Crizotinib, a small molecular tyrosine kinase inhibitor, manifests dramatic
responses in patients with non-small cell lung cancer with echinoderm microtubule
associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements.
ALK gene point mutation is the primary mechanism of acquired crizotinib
resistance; however, the intrinsic mechanism is not fully understood. Here, we
report a patient with a low mutant allele fraction (MAF) of EML4-ALK
rearrangement, who experienced primary resistance to crizotinib treatment. The
patient was a 66-year-old Chinese man, who had a history of metastatic lung
cancer and was treated with first- and third-generation epidermal growth factor
receptor tyrosine kinase inhibitors (EGFR TKIs). After 14 months of osimertinib
treatment, his disease progressed, and next-generation sequencing was performed
from a liquid biopsy of the patient's blood. An EML4-ALK rearrangement was found
and crizotinib was administered. The patient's lung lesions continued to progress
after one month of crizotinib treatment, and pemetrexed-bevacizumab was
initiated. After two cycles of chemotherapy, the metastatic cancers shrunk, and
the patient maintained stable disease at his last follow-up. EML4-ALK
rearrangements can happen in patients with EGFR-positive NSCLC, after acquired
resistance to EGFR TKI treatment. The EGFR T790M and C797G mutations occur in cis
is a critical mechanism of resistance to osimertinib therapy. The MAF of EML4-ALK
rearrangements in cancer cells might be a predictive factor for crizotinib
treatment.
PMID- 29951343
TI - Ovarian cancer presenting with hypercalcemia: two cases with similar
manifestations but different mechanisms.
AB - Hypercalcemia presenting in ovarian cancer is uncommon in the clinic. Here, two
cases of ovarian epithelial carcinoma that presented with severe hypercalcemia
were reported, with a review of the literature. The laboratory findings and
stepwise clinical investigations of these two cases differed, indicating distinct
underlying causes of hypercalcemia. In case one, the serum levels and
immunostaining for parathyroid hormone-related protein (PTHrP) verified humoral
hypercalcemia of malignancy (HHM). In case two, the high level of parathyroid
hormone (PTH) and the scintigraphy scan showing parathyroid gland adenoma
confirmed primary hyperparathyroidism-induced hypercalcemia. Both patients
received optimal cytoreductive operation and adjuvant chemotherapy but showed
different outcomes respectively. This article focused on differential diagnosis
of ovarian cancer-associated hypercalcemia, by stepwise imaging and laboratory
investigation, and the appropriate therapy should be considered based on the
different etiologies.
PMID- 29951344
TI - Effects of irregular respiratory motion on the positioning accuracy of moving
target with free breathing cone-beam computerized tomography.
AB - For positioning a moving target, a maximum intensity projection (MIP) or average
intensity projection (AIP) image derived from 4DCT is often used as the reference
image which is matched to free breathing cone-beam CT (FBCBCT) before treatment.
This method can be highly accurate if the respiratory motion of the patient is
stable. However, a patient's breathing pattern is often irregular. The purpose of
this study is to investigate the effects of irregular respiration on positioning
accuracy for a moving target aligned with FBCBCT. Nine patients' respiratory
motion curves were selected to drive a Quasar motion phantom with one embedded
cubic and two spherical targets. A 4DCT of the phantom was acquired on a CT
scanner (Philips Brilliance 16) equipped with a Varian RPM system. The phase
binned 4DCT images and the corresponding MIP and AIP images were transferred into
Eclipse for analysis. FBCBCTs of the phantom driven by the same respiratory
curves were also acquired on a Varian TrueBeam and fused such that both CBCT and
MIP/AIP images share the same target zero positions. The sphere and cube volumes
and centroid differences (alignment error) determined by MIP, AIP and FBCBCT
images were calculated, respectively. Compared to the volume determined by MIP,
the volumes of the cube, large sphere, and small sphere in AIP and FBCBCT images
were smaller. The alignment errors for the cube, large sphere and small sphere
with center to center matches between MIP and FBCBCT were 2.5 +/- 1.8mm, 2.4+/
2.1 mm, and 3.8+/-2.8 mm, and the alignment errors between AIP and FBCBCT were
0.5+/-1.1mm, 0.3+/-0.8mm, and 1.8+/-2.0 mm, respectively. AIP images appear to be
superior reference images to MIP images. However, irregular respiratory pattern
could compromise the positioning accuracy, especially for smaller targets.
PMID- 29951345
TI - Multiple Breath-hold Volumetric Modulated Arc Therapy Under Fluoroscopic Image
Guidance with an Implanted Fiducial Marker: An Advanced Technique.
AB - An advanced technique for multiple breath-hold volumetric modulated arc therapy
(VMAT) has been proposed under fluoroscopic image guidance with a fiducial marker
implanted close to a tumor. The marker coordinates on a digitally reconstructed
radiography image at a gantry start angle, under a planned breath-hold condition,
were transferred to the fluoroscopic image window. Then, a reference lateral line
passing through the planned breath-hold marker position was drawn on the
fluoroscopic image. Additional lateral lines were further added on both sides of
the reference line with a distance of 3 mm as a tolerance limit for the breath
hold beam delivery. Subsequently, the patient was asked to breathe in slowly
under fluoroscopy. Immediately after the marker position on the fluoroscopic
image moved inside the tolerance range, the patient was asked to hold the breath
and the VMAT beam was delivered. During the beam delivery, the breath-hold status
was continuously monitored by checking if the deviation of the marker position
exceeded the tolerance limit. As long as the marker stayed within the tolerance
range, a segmented VMAT delivery continued for a preset period of 15 to 30
seconds depending on the breath-hold capability of each patient. As soon as each
segmented delivery was completed, the beam interrupt button was pushed;
subsequently, the patient was asked for free breathing. This procedure was
repeated until all the segmented VMAT beams were delivered. A lung tumor case is
reported here as an initial study. The proposed technique may be clinically
advantageous for treating respiratory moving tumors including lung tumor, liver
cancer, and other abdominal cancers.
PMID- 29951346
TI - Isolated Lateral Malleolar Fracture Treated with a Bioabsorbable Magnesium
Compression Screw.
AB - Magnesium (Mg) bioabsorbable screws are new biomaterials used in fracture
fixation. In the current literature, there is only one case report on the use of
magnesium bio-absorbable screws in ankle fractures. Within the present study, a
19-year-old female who sustained an isolated lateral malleolar fracture was
treated with open reduction and intramedullary Mg screw fixation and then
followed up for two years. Fracture union was achieved without any complication
such as failure of fixation, loss of reduction, infection, or any other adverse
reaction. Mg bioabsorbable screws are an alternative method of fracture fixation
as compared to conventional metallic implants since they eliminate the need for
implant removal.
PMID- 29951347
TI - Toward a Resident Personal Finance Curriculum: Quantifying Resident Financial
Circumstances, Needs, and Interests.
AB - Introduction Resident financial health has been linked to wellness and
resiliency, yet financial literacy among residents is highly variable. While some
medical school curricula include budgeting and student loan education, content on
managing finances as a resident is usually lacking. We sought to quantitatively
assess residents' financial circumstances, needs, and interests to inform the
design of a resident personal finance curriculum. Methods Surveys were sent to
residents in eight specialties at an academic medical center. Likert-type
responses allowed respondents to rate their level of comfort (1 = Very
Uncomfortable, 7 = Very Comfortable) and interest (1 = Very Uninterested, 7 =
Very Interested) in various personal finance topics including budgeting, loan
repayment, disability insurance, life insurance, home buying, and retirement
planning. Details regarding financial circumstances, including assets,
liabilities, and insurance, were also collected. Results of questions that
utilized a Likert-type scale are reported as median (interquartile range).
Results Of 346 residents surveyed, 144 (41.6%) responded. Residents were from
Internal Medicine (56, 38.9%), Pediatrics (34, 23.6%), Emergency Medicine (18,
12.5%), and other specialties (36, 25.0%). Ninety-one (63.2%) reported
educational loans, with an average balance of $191,730. Credit card balances
exceeding $3,000 were reported by 11 (7.6%) respondents. One-hundred-two (70.1%)
reported emergency savings, but only 65 (45.1%) reported having a retirement
account (average balance $27,608). Respondents rated highest comfort levels with
budgeting (5[4-6]), and lowest level of comfort with disability insurance (2[2
4]) and home buying (2[2-5]). Interest in learning each topic was high (6[5-7]),
with retirement planning (6[5-7]), investing (6[5-7]), and home buying (6[5-7])
the topics of highest interest. Conclusion These results highlight the deficits
in personal finance literacy among residents. Future work should focus on
development of a nationally scalable personal finance curriculum for residents.
PMID- 29951348
TI - A Rare Case of Dynamic Popliteal Artery Occlusion After Gunshot Injury with
Reconstitution of Flow in the Frog-leg Position.
AB - A 16-year-old male was transferred to our institution shortly after a gunshot
injury to the right lower extremity. Physical examination was remarkable for two
bullet entry points in the right posterior leg. A right lower extremity computed
tomography angiogram (CTA) demonstrated a retained bullet fragment in the right
popliteal fossa and a 10 centimeter (cm) in length occlusion of the proximal
peroneal artery with reconstitution of flow distally. A diagnostic angiogram of
the right lower extremity with the patient's leg extended demonstrated lack of
popliteal arterial flow immediately distal to the retained bullet fragment.
Reconstitution of vascular flow was appreciated once the patient's leg was placed
in the "frog-leg" position.
PMID- 29951349
TI - The importance of sediments in ecological quality assessment of stream
headwaters: embryotoxicity along the Nidda River and its tributaries in Central
Hesse, Germany.
AB - Background: Although the crucial importance of sediments in aquatic systems is
well-known, sediments are often neglected as a factor in the evaluation of water
quality assessment. To support and extend previous work in that field, this study
was conducted to assess the impact of surface water and sediment on fish embryos
in the case of a highly anthropogenically influenced river catchment in Central
Hesse, Germany. Results: The results of 96 h post fertilisation fish embryo
toxicity test with Danio rerio (according to OECD Guideline 236) revealed that
river samples comprising both water and sediment exert pivotal effects in
embryos, whereas surface water alone did not. The most prominent reactions were
developmental delays and, to some extent, malformations of embryos. Developmental
delays occurred at rates up to 100% in single runs. Malformation rates ranged
mainly below 10% and never exceeded 25%. Conclusion: A clear relationship between
anthropogenic point sources and detected effects could not be established.
However, the study illustrates the critical condition of the entire river system
with respect to embryotoxic potentials present even at the most upstream test
sites. In addition, the study stresses the necessity to take into account
sediments for the evaluation of ecosystem health in industrialised areas.
PMID- 29951350
TI - Solitary Infiltrating Meningioma of the Trochlear Nerve: Case Report.
AB - We report the case of a solitary meningioma infiltrating the trochlear nerve, the
first in a patient without a neurocutaneous disorder or cavernous sinus
involvement. The patient presented with diplopia was found to have a focal
enhancing mass encompassing the trochlear nerve. Following surgical resection,
pathological examination showed meningioma infiltrating the nerve itself,
demonstrated on the included pathology images. A review of the literature and
discussion of meningiomas infiltrating cranial nerves are included.
PMID- 29951351
TI - Malignant renal epithelioid angiomyolipoma with TFE3 gene amplification mimicking
renal carcinoma.
AB - Malignant renal epithelioid angiomyolipoma (EAML) is an extremely rare disease
with a poor prognosis, and currently there are no uniform criteria for its
biological behavior. Here, we present a case of malignant renal EAML with TFE3
gene amplification in a 53-year-old woman. Four months after surgery, unenhanced
computed tomography scans showed recurrence as well as metastasis in the abdomen
and lung. The patient succumbed to rapid neoplastic progression of the disease 6
months later.
PMID- 29951352
TI - A multi-jointed underactuated robot hand with fluid-driven stretchable tubes.
AB - Inspired from flexible bending of octopus' tentacles and outside-driving kind of
traditional exoskeletons, this paper proposed a novel self-adaptive underactuated
finger mechanism, called OS finger. OS finger is similar to an octopus' tentacle
and consists of an artificial muscle which is through all joints and driven by
fluid, eight serial-hinged joints, and force-changeable assembly. The force
changeable assembly is mainly composed of a spring and elastic rubber membrane,
which is coordinated for stable grasping by a layer of rubber material in the
surface of the finger. OS finger can execute different grasping modes depending
on the shapes and dimensions of the grasped objects and grip objects in a gentle
and form-fitting manner. The OS finger combines good qualities of both rigid
grasp of traditional fingers and form-fitting grasp of flexible fingers.
Kinematic analysis and experimental results show that the OS robot Hand with four
OS fingers is valid for precise pinching, self-adaptive powerful encompassing,
and grasping forces that are freely changeable in a wide range. With the
advantage of high self-adaptation, various grasp configurations and large range
of grasping forces, the OS Hand has a wide range of applications in the area of
service robotics which requires a lot of flexible operations of general grasping,
moving and releasing.
PMID- 29951354
TI - Associations of mode of travel to work with physical activity, and individual,
interpersonal, organisational, and environmental characteristics.
AB - Introduction: Encouraging walking during the daily commute is a potential
strategy for increasing physical activity levels. This study aimed: (i) to
examine, and compare by travel mode, the objectively measured physical activity
of a working adult population, and, (ii) to identify associations between mode of
travel to work and a range of individual, interpersonal, organisational and
environmental characteristics. Methods: Employees (n=654) recruited from 87
workplaces in geographically distinct areas provided data through accelerometers,
Global Positioning System (GPS) receivers, travel diaries and questionnaires.
Separate multivariable logistic regression models were developed to examine
factors associated with physical activity during the commute and mode of travel
to work. Results: In comparison to car users (7.3 minutes+/-Standard Deviation
7.6), walkers (34.3+/-18.6) and public transport users (25.7+/-14.0) accrued
substantially higher levels of daily moderate to vigorous physical activity
during the commute. Combined accelerometer and GPS data showed that participants
who walked at least ten minutes during their commute were more likely to have a
shorter commute distance (p<0.001), occupy a sedentary job (p<0.01), and be
classified as 'underweight or normal weight' (p<0.03). No car access (p<0.001),
and absence of free work car parking (p<0.01) were independently related to
walking to work and using public transport. Shorter commuting distances were also
related to walking to work (p<0.001). Public transport users were more likely to
be younger (p=0.04), have more positive environmental perceptions (p=0.01), and
less likely to combine their commute with caring responsibilities (p=0.03).
Conclusions: This study shows that walking to work and using public transport are
important contributors to physical activity levels in a working population.
Planning, transport and behavioural interventions to promote walking during the
commute should take into account the wider determinants. Reducing availability of
free work car parking is one possible strategy to discourage car use.
PMID- 29951353
TI - Store-Operated Ca2+ Entry as a Prostate Cancer Biomarker - a Riddle with
Perspectives.
AB - Purpose of Review: Store-operated calcium entry (SOCE) is dysregulated in
prostate cancer, contributing to increased cellular migration and proliferation
and preventing cancer cell apoptosis. We here summarize findings on gene
expression levels and functions of SOCE components, stromal interaction molecules
(STIM1 and STIM2), and members of the Orai protein family (Orai1, 2, and 3) in
prostate cancer. Moreover, we introduce new research models that promise to
provide insights into whether dysregulated SOCE signaling has clinically relevant
implications in terms of increasing the migration and invasion of prostate cancer
cells. Recent Findings: Recent reports on Orai1 and Orai3 expression levels and
function were in part controversial probably due to the heterogeneous nature of
prostate cancer. Lately, in prostate cancer cells, transient receptor melastatin
4 channel was shown to alter SOCE and play a role in migration and proliferation.
We specifically highlight new cancer research models: a subpopulation of cells
that show tumor initiation and metastatic potential in mice and zebrafish models.
Summary: This review focuses on SOCE component dysregulation in prostate cancer
and analyzes several preclinical, cellular, and animal cancer research models.
PMID- 29951355
TI - Risk of Cardiovascular Events in Patients with Primary Biliary Cholangitis -
Systematic Review.
AB - Background and Aims: Hypercholesterolemia is a common finding in patients with
primary biliary cholangitis (PBC) and is a well-defined risk factor for
cardiovascular disease. However, studies have been mixed on whether PBC patients
do, in fact, have higher cardiovascular risk. The aim of this study is to review
the current literature and provide an evidence-based assessment of cardiovascular
risk in PBC patients. Methods: We performed a systematic literature search on
PubMed regarding patients with PBC and cardiovascular events from the database
inception to July 1, 2017. A total of 33 articles fulfilling our inclusion
criteria were found. Results: The majority of the studies evaluated yielded no
statistically significant difference in cardiovascular disease in the PBC
population compared to the general public. However, some reports found a
statistically significantly increase in coronary artery disease. Several studies
have looked at the specific lipid profile of patients with PBC with
hypocholesteremia. While these lipid abnormalities differ by stage of disease,
there is evidence to suggest that the specific lipid profile in PBC may have
lower atherogenicity than in patients with hypercholesterolemia without PBC.
Studies looking at patients with PBC with other risk factors for cardiovascular
disease, such as hypertension and metabolic syndrome, have consistently found a
higher risk for cardiovascular disease in these patients. Statin treatment is
effective in reducing lipid levels and possibly improving endothelial
inflammation in patients with PBC with hypercholesterolemia. Conclusions: There
is not enough evidence to suggest an increased risk of cardiovascular disease in
patients with PBC with hypercholesterolemia, except for those individuals with
concomitant features of metabolic syndrome. In patients with PBC with no
additional cardiovascular risk factors, individual risk/benefit discussion on
lipid-lowering treatment should be considered.
PMID- 29951356
TI - Glycosphingolipids Prevent APAP and HMG-CoA Reductase Inhibitors-mediated Liver
Damage: A Novel Method for "Safer Drug" Formulation that Prevents Drug-induced
Liver Injury.
AB - Background and Aims: Acetaminophen (APAP) and HMG-CoA reductase inhibitors are
common causes of drug-induced liver injury (DILI). This study aimed to determine
the ability to reduce APAP- and statins-mediated liver injury by using
formulations that combine glycosphingolipids and vitamin E. Methods: Mice were
injected with APAP or with statins and treated before and after with beta
glucosylceramide (GC), with or without vitamin E. Mice were followed for changes
in liver enzymes, liver histology, hepatic expression of JNK, STAT3 and caspase
3, as well as intrahepatic natural killer T cells (NKT) and the serum cytokine
levels by flow cytometry. Results: Administration of GC before or after APAP
alleviated the liver damage, as noted by a reduction of the liver enzymes,
improvement in the liver histology and decreased hepatic caspase 3 expression.
Beneficial effect was associated with a reduction of the intrahepatic NKT, JNK
expression in the liver, and increased glutathione in the liver, and decreased
TNF-alpha serum levels. Synergistic effect of co-administration of GC with
vitamin E was observed. Similar protective effect of GC on statin-mediated liver
damage was documented by a reduction in liver enzymes and improved liver
histology, which was mediated by reduction of NKT, increased STAT3 expression in
the liver, and reduced the TGF-beta and IL17 levels. Conclusions: beta
glycosphingolipids exert a hepatoprotective effect on APAP- and statins-mediated
liver damage. Vitamin E exerted a synergistic effect to that of GC. The
generation of "safer drug" formulations, which include an active molecule
combined with a hepatoprotective adjuvant, may provide an answer to the real
unmet need of DILI.
PMID- 29951357
TI - Vitamin D Deficiency and Its Relationship with Child-Pugh Class in Patients with
Chronic Liver Disease.
AB - Background and Aims: Skeletal manifestation in liver diseases represents the
minimally scrutinized part of the disease spectrum. Vitamin D deficiency has a
central role in developing hepatic osteodystrophy in patients with chronic liver
disease. This study aimed to investigate vitamin D levels and their relationship
with disease advancement in these patients. Methods: Vitamin D levels were
checked in 125 chronic liver disease patients. The patients were classified in
three stages according to Child-Pugh score: A, B and C. The relationship of
vitamin D levels with Child-Pugh score and other variables in the study was
assessed by the contingency coefficient. Correlation and logistic regression
analyses were also carried out to find additional predictors of low vitamin D
levels. Results: Among the patients, 88% had either insufficient or deficient
stores of vitamin D, while only 12% had sufficient vitamin D levels (p >0.05).
Vitamin D levels were notably related to Child-Pugh class (contingency
coefficient = 0.5, p <0.05). On univariate and multinomial regression analyses,
age, female sex, MELD and Child-Pugh class were predictors of low vitamin D
levels. Age, model of end-stage liver disease score and Child-Pugh score were
negatively correlated to vitamin D levels (p <0.05). Conclusions: Vitamin D
deficiency is notably related to age, female sex and model of end-stage liver
disease score, in addition to Child-Pugh class of liver cirrhosis. Vitamin D
levels should be routinely checked in patients with advanced liver cirrhosis
(Child-Pugh class B and C) and this deficiency must be addressed in a timely
manner to improve general well-being of cirrhotic patients.
PMID- 29951358
TI - Effect of Genistein in Comparison with Trichostatin A on Reactivation of DNMTs
Genes in Hepatocellular Carcinoma.
AB - Background and Aims: DNA methylation and histone modification are epigenetic
modifications essential for normal function of mammalian cells. The processes are
mediated by biochemical interactions between DNA methyltransferases (DNMTs) and
histone deacetylases. Promoter hypermethylation and deacetylation of tumor
suppressor genes play major roles in cancer induction, through transcriptional
silencing of these genes. DNA hypermethylation is carried out by a family of
DNMTs including DNMT1, DNMT3a and DNMT3b. In hepatocellular carcinoma, a
significant positive correlation between over-expression of these genes and
cancer induction has been reported. The DNA demethylating agent genistein (GE)
has been demonstrated to reduce different cancers. Previously, we reported that
GE can induce apoptosis and inhibit proliferation in hepatocellular carcinoma
PLC/PRF5 and HepG2 cell lines. Besides, histone deacetylase inhibitors, such as
trichostatin A (TSA), were successfully used to inhibit cancer cell growth. The
present study was designed to assess the effect of GE in comparison with TSA on
DNMT1, DNMT3a and DNMT3b gene expression, cell growth inhibition and apoptosis
induction in the HepG2 cell line. Methods: Cells were seeded and treated with
various doses of GE and TSA. The MTT assay, flow cytometry assay, and real-time
RT-PCR were used to determine viability, apoptosis, and DNMT1, DNMT3a and DNMT3b
gene expression respectively. Results: Both agents inhibited cell growth, induced
apoptosis and reactivated DNMT1, DNMT3a and DNMT3b gene expression. Furthermore,
TSA demonstrated a significantly greater apoptotic effect than the other agent,
whereas GE improved gene expression more significantly than TSA. Conclusions: Our
findings suggest that GE and TSA can significantly inhibit cell growth, induce
apoptosis and restore DNMT1, DNMT3a and DNMT3b gene reactivation.
PMID- 29951359
TI - HCV Therapy Follow-up Fractionation (CTF2) by Intra-PBMC Nested RNA PCR
Recognizes Early Virologic Response and Relapse.
AB - Background and Aims: Sustained virologic response is evaluated by single-step
reverse transcription (SRT) PCR assay, which assesses hepatitis C virus (HCV)
clearance from plasma but not from tissues such as peripheral blood mononuclear
cells (PBMCs). Persistence of HCV RNA in PBMCs beyond end of treatment (EOT) is
associated with nonresponse. Our goal was to measure intra-PBMC HCV RNA levels
during oral antiviral therapy according to the HCV therapy follow-up
fractionation (CTF2) protocol. Methods: Compensated chronic HCV patients (n = 2
78 SRT-PCR positive) were scheduled to receive oral antiviral therapy. Subjects
were followed-up by SRT and intra-PBMCs HCV RNA PCR at the end of the 2nd, 6th,
10th, 14th, 18th and 24th weeks to evaluate virus clearance from plasma and
PBMCs, respectively. The CTF2 protocol evaluated SRT and PBMC PCR status at each
follow-up point for determining therapy continuation or interruption to address
cost effectiveness. Results: All patients tested negative by SRT PCR after
therapy for 2 weeks. Application of the CTF2 protocol revealed: a) increasing HCV
clearance rate from 75.9% at the end of 10th week to 90.3% at the end of 24th
week (p < 0.00001); b) faster clearance of HCV from plasma compared to PBMCs at
each point of follow-up until the 18th week (p < 0.05); c) higher viral
elimination rates diagnosed by PBMC HCV RNA PCR(-) compared to PBMC HCV RNA
PCR(+) from the 6th to 24th week of treatment (p < 0.0001); d) higher over-time
increase curve of combined plasma and PBMC HCV RNA determined negativity compared
to the decline in positivity curves by PBMC PCR at the 6th-18th week compared to
the 24th week (p < 0.01)-these results validated treatment continuation; and e)
solitary evaluation of EOT sustained HCV infection and relapses by PBMC HCV RNA
(p < 0.001). Conclusions: Early elimination of serum and tissue (PBMC) HCV
infection by oral antiviral therapy can be achieved and evaluated during a cost
effective CTF2 protocol application.
PMID- 29951360
TI - Occult Hepatitis C Virus Infection: A Review.
AB - Occult hepatitis C virus (HCV) infection (OCI), first described in 2004, is
defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear
cells without detectable HCV RNA in the serum. Here, we aimed to review the
epidemiology, diagnostic methods, clinical implications and potential management
recommendations currently described in the literature, as well as the future
directions for investigation of this entity. PubMed and Cochrane databases were
searched with combination of the following keywords: "occult", "hepatitis C
virus", and "occult HCV infection". There are data to support OCI as a potential
culprit in cryptogenic liver disease. There are also consistent data
demonstrating the existence of OCI in specific populations, such as dialysis,
human immunodeficiency virus-infected and hepatitis B virus-infected patients,
and also in the general population. While the gold standard for diagnosis is
liver biopsy, examination of peripheral blood mononuclear cells may be a
reliable, safer alternative method of diagnosis. Occult HCV infection is likely
associated with liver fibrosis and progression of liver disease. Additional
studies are required to determine the infectivity of OCI patients, as well as
clarify the natural course and specific clinical implications of OCI. Lastly,
studies are needed to determine whether treatment of OCI leads to decreased
morbidity and/or mortality.
PMID- 29951361
TI - Cardiovascular Involvement in Chronic Hepatitis C Virus Infections - Insight from
Novel Antiviral Therapies.
AB - Whereas statistical association of hepatitis C virus (HCV) infection with
cardiomyopathy is long known, establishment of a causal relationship has not been
achieved so far. Patients with advanced heart failure (HF) are mostly unable to
tolerate interferon (IFN)-based treatment, resulting in limited experience
regarding the possible pathogenic role of HCV in this patient group. HCV
infection often triggers disease in a broad spectrum of extrahepatic organs, with
innate immune and autoimmune pathogenic processes involved. The fact that
worldwide more than 70 million patients are chronically infected with HCV
illustrates the possible clinical impact arising if cardiomyopathies were induced
or aggravated by HCV, resulting in progressive HF or severe arrhythmias. A novel
path has been opened to finally resolve the long-standing question of cause
effect relationship between HCV infection and cardiac dysfunction, by the recent
development of IFN-free, highly efficient, and well tolerable anti-HCV regimens.
The new direct-acting antiviral (DAA) agents are highly virus-specific and lack
unspecific side-effects upon cardiac function which have always confounded the
interpretation of IFN treatment data. The actual frequency of unexplained HF in
chronic HCV infection will be determined from a planned large-scale study.
Whereas such patients probably constitute a rather small fraction of all those
harboring HCV, they have major clinical relevance. It is not yet known which
fraction of these patients will significantly benefit from HCV eradication, but
this issue will be addressed now in a prospective study.
PMID- 29951362
TI - Non-alcoholic Fatty Liver Disease: A Review of Anti-diabetic Pharmacologic
Therapies.
AB - Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver
disease, affects approximately 75 to 100 million Americans. Patients with
concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing
to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics.
Lifestyle modifications, including weight loss, remain the mainstay of treatment
for NAFLD, as there are no medications currently indicated for this disease
state. Anti-diabetic pharmacologic therapies aimed at improving insulin
sensitivity and decreasing insulin production have been studied to determine
their potential role in slowing the progression of NAFLD. In this review, we
focus on the evidence surrounding anti-diabetic medications and their ability to
improve disease progression in patients with NAFLD.
PMID- 29951363
TI - Hepatocellular Carcinoma: Diagnosis, Treatment Algorithms, and Imaging Appearance
after Transarterial Chemoembolization.
AB - Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, with
incidence increasing worldwide. Unfortunately, the overall prognosis for patients
with HCC is poor and many patients present with advanced stages of disease that
preclude curative therapies. Diagnostic and interventional radiologists play a
key role in the management of patients with HCC. Diagnostic radiologists can use
contrast-enhanced computed tomography (CT), magnetic resonance imaging, and
ultrasound to diagnose and stage HCC, without the need for pathologic
confirmation, by following established criteria. Once staged, the interventional
radiologist can treat the appropriate patients with percutaneous ablation,
transarterial chemoembolization, or radioembolization. Follow-up imaging after
these liver-directed therapies for HCC can be characterized according to various
radiologic response criteria; although, enhancement-based criteria, such as
European Association for the Study of the Liver and modified Response Evaluation
Criteria in Solid Tumors, are more reflective of treatment effect in HCC. Newer
imaging technologies like volumetric analysis, dual-energy CT, cone beam CT and
perfusion CT may provide additional benefits for patients with HCC.
PMID- 29951364
TI - Post Locoregional Therapy Treatment Imaging in Hepatocellular Carcinoma Patients:
A Literature-based Review.
AB - Imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC)
as well as in determining treatment efficacy, or complications, following
therapy. Unlike other cancers, HCC is most commonly treated by locoregional
therapies (LRTs) such as thermal ablation, transarterial chemoembolization, and
transarterial radioembolization. These treatments can lead to changes on imaging
that make determination of residual/recurrent disease difficult. This literature
based review discusses the expected postimaging findings following LRT.
PMID- 29951365
TI - Non-invasive in vivo Imaging Grading of Liver Fibrosis.
AB - Liver fibrosis (LF), a common consequence of chronic liver diseases with various
etiologies, is characterized by excessive accumulation of macromolecules,
including collagen, glycoproteins and proteoglycans, in the liver. LF can result
in hepatic dysfunction, cirrhosis, portal hypertension and, in some cases,
hepatocellular carcinoma. As the current gold standard for diagnosing LF, liver
biopsy, however, is invasive and prone to sampling errors and procedure-related
complications. Therefore, developing noninvasive, precise and reproducible
imaging tests for diagnosing and staging LF is of great significance.
Conventional ultrasound (US), computed tomography (CT) and magnetic resonance
(MR) imaging can depict morphological alterations of advanced LF, but have
relatively limited capability characterizing early-stage LF. In order to optimize
the diagnostic performances of noninvasive imaging techniques for LF across its
entire spectrum of severity, a number of novel methods, including US
elastography, CT perfusion imaging and various MR imaging-based techniques, have
been established and introduced to clinical practice. In this review, we intended
to summarize current noninvasive imaging techniques for LF, with special emphasis
on the possible roles, advantages and limitations of the new emerging imaging
modalities.
PMID- 29951366
TI - Differentiating Cystic Liver Lesions: A Review of Imaging Modalities, Diagnosis
and Management.
AB - Hepatic cysts (HCs) are frequently discovered incidentally on abdominal imaging.
The prevalence of HCs has been reported as high as 15-18% in the United States.
Although most cysts are benign, some are malignant or premalignant. It is
important to diagnose cystic lesions in order to properly manage them. Imaging
with conventional ultrasound, computed tomography, magnetic resonance imaging, or
contrast-enhanced ultrasound can be used to further characterize and diagnose
HCs. Ultrasound is typically the first-line imaging modality, whereas more
advanced imaging can help narrow down the specific lesion. Contrast-enhanced
ultrasound is a newer modality, recently approved in the United States, which
offers non-invasive evaluation in real-time. The first step in diagnosis is
stratifying risk by differentiating simple and complex cysts. There are several
features that can help identify HCs, including septae, mural consistency,
calcifications, and quality of cystic fluid. Simple cysts are mainly congenital
cysts, but also occur in polycystic liver disease. Complex cysts include mucinous
neoplasms, echinococcal cysts, hemorrhagic cysts, cystic hepatocellular carcinoma
and other rare lesions. Treatment is indicated in symptomatic cysts or those
suspicious for malignant or premalignant features. Treatment modalities include
fenestration, aspiration sclerotherapy, or surgical resection.
PMID- 29951367
TI - Noninvasive Quantitative Detection Methods of Liver Fat Content in Nonalcoholic
Fatty Liver Disease.
AB - Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to NAFLD
related liver cirrhosis and is a main cause of chronic liver diseases. Patients
with nonalcoholic steatohepatitis and fibrosis are at a great risk of the
progression to cirrhosis or hepatocellular carcinoma, both of which are tightly
associated with liver-related mortality. Liver biopsy is still the gold standard
for the diagnosis of NAFLD, but some defects, such as serious complications,
sampling error and variability in histologic evaluation among pathologists,
remain problematic. Therefore, noninvasive, repeatable and accurate diagnostic
methods are urgently needed. Ultrasonography is a well-established and lower-cost
imaging technique for the diagnosis of hepatic steatosis, especially suitable for
population census, but limited by its low sensitivity to diagnose mild steatosis
and being highly operator-dependent. Computed tomography also lacks the
sensitivity to detect mild steatosis and small changes in fat content, and
presents a potential radiation hazard. Controlled attenuation parameter based on
the FibroScan(r) technology is a promising tool for noninvasive semiquantitative
assessment of liver fat content, but the accuracy rate depends on the operator's
expertise and is affected by age, width of the intercostal space, skin capsular
distance and body mass index. Magnetic resonance imaging and magnetic resonance
spectroscopy are regarded as the most accurate quantitative methods for measuring
liver fat content in clinical practice, especially for longitudinal follow up of
NAFLD patients. In this review, we mainly introduce the current imaging methods
that are in use for evaluation of liver fat content and we discuss the advantages
and disadvantages of each method.
PMID- 29951369
TI - Ribavirin in Acute Hepatitis E Infection in Patients with Gynecological Cancer: A
Case Series.
AB - Hepatitis E virus infection is usually a self-limited disease. However, during
the last years there has been growing evidence for prolonged and chronic
infection occurring in patients with immunosuppression. Also patients with
malignant and rheumatic diseases have been identified to be at risk for chronic
hepatitis E. However, their course and prognosis are not well characterized and
there have been no reports of hepatitis E virus infection in patients with
gynecological cancer. Here, we report three Caucasian females with breast and
ovarian cancers presenting with elevation of aminotransferase levels during
anticancer treatment. Although only few or no clinical hints suggested hepatitis
E virus infection, the diagnosis of hepatitis E virus infection was confirmed by
seroconversion, which might occur with some delay, and/or by polymerase chain
reaction. While two patients had a self-limited course, the third patient with a
high-risk oncological constellation required ribavirin in order to resume
chemotherapy. These cases highlight the need for hepatitis E virus testing in
patients with gynecological cancer and elevated aminotransferase levels. Further,
these cases show that in selected high-risk patients, ribavirin treatment may be
necessary based on the decision of a multidisciplinary team.
PMID- 29951368
TI - CT-MRI LI-RADS v2017: A Comprehensive Guide for Beginners.
AB - Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and
the second leading cause of cancer-related deceases worldwide. Early diagnosis is
essential for correct management and improvement of prognosis. Proposed for the
first time in 2011 and updated for the last time in 2017, the Liver Imaging
Reporting and Data System (LI-RADS) is a comprehensive system for standardized
interpretation and reporting of computed tomography (CT) and magnetic resonance
imaging (MRI) liver examinations, endorsed by the American College of Radiology
to achieve congruence with HCC diagnostic criteria in at-risk populations.
Understanding its algorithm is fundamental to correctly apply LI-RADS in clinical
practice. In this pictorial review, we provide a guide for beginners, explaining
LI-RADS indications, describing major and ancillary features and eventually
elucidating the diagnostic algorithm with the use of some clinical examples.
PMID- 29951370
TI - Cancer Incidence in Europe: An Ecological Analysis of Nutritional and Other
Environmental Factors.
AB - The aim of this work was to offer an ecological alternative to conventional
observational studies and identify factors potentially associated with cancer
incidence in Europe. The incidence of 24 types of cancer in 39 European countries
(2012) was compared with a long-term mean supply of 68 food items from the
FAOSTAT database (1993-2011) and some other variables such as smoking, body mass
index, raised cholesterol, and socioeconomic indicators. In addition to simple
Pearson linear correlations, the data were analyzed via factor analyses and
penalized regression methods. This comparison identified two main groups of
cancers that are characteristically associated with the same variables. The first
group consists of cancers of the prostate, breast, white blood cells, and
melanoma. Their incidence increases with rising gross domestic product (GDP) per
capita, a prevalence of raised cholesterol and a high intake of animal products.
The second group includes primarily cancers of the digestive tract and is most
consistently correlated with alcoholic beverages, lard, and eggs. In addition, we
found specific correlations between certain variables and some other types of
cancer (smoking-lung and larynx cancer; low GDP per capita and high carbohydrate
consumption-stomach and cervical cancer; tea drinking-esophageal cancer; maize
consumption and wine drinking-liver cancer). The documented findings often
remarkably agree with the current scientific consensus, and when combined with
evidence based on different methodologies, they can further extend our knowledge
of the etiology of cancer. In addition, our study also identifies several foods
with possible preventive effects and indicates that various dairy products may
markedly differ in their relationship to cancer incidence. All these data can
potentially be of fundamental importance for clinical practice and the survival
of cancer patients.
PMID- 29951371
TI - microRNA-494 Favors HO-1 Expression in Neuroblastoma Cells Exposed to Oxidative
Stress in a Bach1-Independent Way.
AB - Heme oxygenase 1 (HO-1) is crucially involved in cell adaptation to oxidative
stress and has been demonstrated to play an important role in cancer progression
and resistance to therapies. We recently highlighted that undifferentiated
neuroblastoma (NB) cells are prone to counteract oxidative stress through the
induction of HO-1. Conversely, differentiated NB cells were more sensitive to
oxidative stress since HO-1 was scarcely upregulated. In this work, we
investigated the role played by miR-494, which has been proved to be involved in
cancer biology and in the modulation of oxidative stress, in the upregulation of
HO-1. We showed that NB differentiation downregulates miR-494 level. In addition,
endogenous miR-494 inhibition in undifferentiated cells impairs HO-1 induction in
response to exposure to 500 uM H2O2, reducing the number of viable cells. The
analysis of Bach1 expression did not reveal any significant modifications in any
experimental conditions tested, proving that the impairment of HO-1 induction
observed in cells treated with miR-494 inhibitor and exposed to H2O2 is
independent from Bach1. Our results underline the role played by miR-494 in
favoring HO-1 induction and cell adaptation to oxidative stress and contribute to
the discovery of new potential pharmacological targets to improve anticancer
therapies.
PMID- 29951372
TI - Epstein-Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1
Oncogene Among Healthy Population: An Update.
AB - The Epstein-Barr virus (EBV) is a DNA lymphotropic herpesvirus and the causative
agent of infectious mononucleosis. EBV is highly prevalent since it affects more
than 90% of individuals worldwide and has been linked to several malignancies
including PTLDs, which are one of the most common malignancies following
transplantation. Among all the EBV genes, most of the recent investigations
focused on studying the LMP-1 oncogene because of its high degree of polymorphism
and association with tumorigenic activity. There are two main EBV genotypes, Type
1 and 2, distinguished by the differences in the EBNA-2 gene. Further sub
genotyping can be characterized by analyzing the LMP-1 gene variation. The virus
primarily transmits through oral secretions and persists as a latent infection in
human B-cells. However, it can be transmitted through organ transplantations and
blood transfusions. In addition, symptoms of EBV infection are not
distinguishable from other viral infections, and therefore, it remains
questionable whether there is a need to screen for EBV prior to blood
transfusion. Although the process of leukoreduction decreases the viral copies
present in the leukocytes, it does not eliminate the risk of EBV transmission
through blood products. Here, we provide a review of the EBV epidemiology and the
genetic variability of the oncogene LMP-1. Then, we underscore the findings of
recent EBV seroprevalence and viremia studies among blood donors as a highly
prevalent transfusion transmissible oncovirus.
PMID- 29951373
TI - Targeting the Immune Microenvironment in Acute Myeloid Leukemia: A Focus on T
Cell Immunity.
AB - Immunotherapies, such as chimeric antigen receptor T cells, bispecific
antibodies, and immune checkpoint inhibitors, have emerged as promising
modalities in multiple hematologic malignancies. Despite the excitement
surrounding immunotherapy, it is currently not possible to predict which patients
will respond. Within solid tumors, the status of the immune microenvironment
provides valuable insight regarding potential responses to immune therapies. Much
less is known about the immune microenvironment within hematologic malignancies
but the characteristics of this environment are likely to serve a similar
predictive role. Acute myeloid leukemia (AML) is the most common hematologic
malignancy in adults, and only 25% of patients are alive 5 years following their
diagnosis. There is evidence that manipulation of the immune microenvironment by
leukemia cells may play a role in promoting therapy resistance and disease
relapse. In addition, it has long been documented that through modulation of the
immune system following allogeneic bone marrow transplant, AML can be cured, even
in patients with the highest risk disease. These concepts, along with the poor
prognosis associated with this disease, have encouraged many groups to start
exploring the utility of novel immune therapies in AML. While the implementation
of these therapies into clinical trials for AML has been supported by preclinical
rationale, many questions still exist surrounding their efficacy, tolerability,
and the overall optimal approach. In this review, we discuss what is known about
the immune microenvironment within AML with a specific focus on T cells and
checkpoints, along with their implications for immune therapies.
PMID- 29951374
TI - Exploring Small Extracellular Vesicles for Precision Medicine in Prostate Cancer.
AB - Tumor microenvironment constitutes a complex network in which tumor cells
communicate among them and with stromal and immune cells. It has been shown that
cancer cells are able to exchange genetic materials through small extracellular
vesicles (EVs), a heterogeneous group of vesicles with different size and shape,
cargo content, and function. The importance to investigate populations of
circulating EVs would be of great importance as prostate cancer (PCa) biomarkers.
In several neoplasms as well as in PCa, nanometer-sized EVs of endosomal origin
are implicated in supporting tumor growth and metastatic spread by both altering
local stroma cells and creating a protumor environment that favors the formation
of pre-metastatic niches. Several techniques are applicable for the isolation and
analysis of PCa-derived small EVs and are illustrated in this article. Due to the
high sensitivity and specificity of these techniques, small EVs have become ideal
candidates for early diagnosis. Moreover, we discuss the role of small EVs during
PCa carcinogenesis, as well as in modulating the development of drug resistance
to hormonal therapy and chemotherapy, thus underlining the potential of EV
tailored strategies in PCa patients.
PMID- 29951377
TI - The immune profile in HIV: A useful signature in future HIV research?
PMID- 29951376
TI - Cas1 and Cas2 From the Type II-C CRISPR-Cas System of Riemerella anatipestifer
Are Required for Spacer Acquisition.
AB - Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR
associated (Cas) proteins provide acquired genetic immunity against the entry of
mobile genetic elements (MGEs). The immune defense provided by various subtypes
of the CRISPR-Cas system has been confirmed and is closely associated with the
formation of immunological memory in CRISPR arrays, called CRISPR adaptation or
spacer acquisition. However, whether type II-C CRISPR-Cas systems are also
involved in spacer acquisition remains largely unknown. This study explores and
provides some definitive evidence regarding spacer acquisition of the type II-C
CRISPR-Cas system from Riemerella anatipestifer (RA) CH-2 (RA-CH-2). Firstly,
introducing an exogenous plasmid into RA-CH-2 triggered spacer acquisition of RA
CRISPR-Cas system, and the acquisition of new spacers led to plasmid instability
in RA-CH-2. Furthermore, deletion of cas1 or cas2 of RA-CH-2 abrogated spacer
acquisition and subsequently stabilized the exogenous plasmid, suggesting that
both Cas1 and Cas2 are required for spacer acquisition of RA-CH-2 CRISPR-Cas
system, consistent with the reported role of Cas1 and Cas2 in type I-E and II-A
systems. Finally, assays for studying Cas1 nuclease activity and the interaction
of Cas1 with Cas2 contributed to a better understanding of the adaptation
mechanism of RA CRISPR-Cas system. This is the first experimental identification
of the naive adaptation of type II-C CRISPR-Cas system.
PMID- 29951378
TI - Phenotypic typing and epidemiological survey of antifungal resistance of Candida
species detected in clinical samples of Italian patients in a 17 months' period.
AB - Introduction: Yeast pathogens are emerging agents of nosocomial as well as
community-acquired infections and their rapid and accurate identification is
crucial for a better management of high-risk patients and for an adequate
treatment. Methods: We performed a retrospective review of 156 yeast isolates
collected during a 17 months' period of regular clinical practice at the
Microbiology Department of San Camillo Hospital in Treviso, Italy and analyzed by
the traditional culture-based method combined with matrix-assisted laser
desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Results:
Out of all the samples collected MALDI-TOF MS was able to characterize with a MT
score >=1.7 (accurate result at species level) 12 different yeast and yeast-like
species from 140 samples: Candida albicans (63.7%), Candida glabrata (13.6%),
Saccharomyces cerevisiae (6.5%), Candida parapsilosis (5.7%), Candida tropicalis
(2.1%), Candida pararugosa (2.1%), Candida guilliermondii (2.1%), Candida kefyr
(1.4%), Candida lusitaniae (0.7%), Candida palmioleophila (0.7%), Geotrichum
silvicola (0.7%), Rhodotorula mucilaginosa (0.7%). Susceptibility testing toward
seven common antifungal agents showed a characteristic MIC distribution of C.
albicans isolates for echinocandins: particularly we noticed that 72% and 46% of
C. albicans showed an MIC value close to clinical breakpoint as defined by
EUCAST, respectively for anidulafungin and micafungin. Conclusion: Accurate
identification of microorganisms and the study of their antifungal susceptibility
allow to understand the epidemiology of a particular area, permitting the choice
of the most appropriate early antifungal treatment.
PMID- 29951375
TI - Extracellular Vesicles in Prostate Cancer Carcinogenesis, Diagnosis, and
Management.
AB - Extracellular vesicles (EVs), especially exosomes, are now well recognized as
major ways by which cancer cells interact with each other and stromal cells. The
meaningful messages transmitted by the EVs are carried by all components of the
EVs, i.e., the membrane lipids and the cargo (DNAs, RNAs, microRNAs, long non
coding RNAs, proteins). They are clearly part of the armed arsenal by which
cancer cells obtain and share more and more advantages to grow and conquer new
spaces. Identification of these messages offers a significant opportunity to
better understand how a cancer occurs and then develops both locally and
distantly. But it also provides a powerful means by which cancer progression can
be detected and monitored. In the last few years, significant research efforts
have been made to precisely identify how the EV trafficking is modified in cancer
cells as compared to normal cells and how this trafficking is altered during
cancer progression. Prostate cancer has not escaped this trend. The aim of this
review is to describe the results obtained when assessing the meaningful content
of prostate cancer- and stromal-derived EVs in terms of a better comprehension of
the cellular and molecular mechanisms underlying prostate cancer occurrence and
development. This review also deals with the use of EVs as powerful tools to
diagnose non-indolent prostate cancer as early as possible and to accurately
define, in a personalized approach, its present and potential aggressiveness, its
response to treatment (androgen deprivation, chemotherapy, radiation, surgery),
and the overall patients' prognosis.
PMID- 29951379
TI - Incidence and predictors of tenofovir disoproxil fumarate-induced renal
impairment in HIV infected Nigerian patients.
AB - Introduction: The use of tenofovir disoproxil fumarate (TDF) in the treatment of
HIV infection has been associated with renal dysfunction. In Nigeria, data on the
incidence and risk factors of TDF nephrotoxicity is sparse. We determined the
cumulative incidence of and risk factors for TDF-induced renal impairment in HIV
infected individuals accessing care at the antiretroviral therapy (ART) clinic of
Jos University Teaching Hospital, Nigeria. Methods: This retrospective cohort
analysis included patients aged >=16 years that initiated ART between January
2008 and December 2011. Renal impairment, defined as glomerular filtration rate
GFR <60 mL/min/1.73 sqm using the Modification of Diet in Renal Disease (MDRD)
equation was assessed at baseline and at 48 weeks on ART. Logistic regression was
performed to determine factors associated with incident renal impairment.
Results: The mean age was 39+/-9 years, and 67.1% were female. The cumulative
incidence of renal impairment among the TDF-exposed and TDF-unexposed groups was
4.6% and 2.3% respectively (p<0.001). TDF exposure was significantly associated
with renal impairment [OR=2.0, 95%CI=(1.48-2.89), p<0.001] in bivariate analysis.
In multivariate analysis, older age (aOR=1.06, 95%CI=(1.05-1.08), p<0.001), TDF
exposure [aOR=1.85, 95%CI=(1.31-2.60), p<0.001] and co-morbidities [aOR=2.71,
95%CI=(1.72-4.25), p<0.001] were significantly associated with renal impairment.
Conclusion: TDF exposure, aging and comorbidities were predictors of renal
toxicity among HIV positive patients. Regular monitoring of renal function in
such high-risk individuals is recommended.
PMID- 29951380
TI - Occurrence, molecular and antimicrobial resistance of Enterococcus spp. isolated
from raw cow's milk trade by street trading in Meknes city, Morocco.
AB - Background: Enterococcus spp. belongs to a group of pathogens which are
responsible for serious infections. This study aims at highlighting the raw milk
microbiological contamination and at providing data for prevalence and
antimicrobial resistance of Enterococcus spp. isolated from raw cow's milk
marketed (without any pasteurization) by street traders. Methods: During the
period of May 2015 through April 2016, 150 cow's raw milk samples were collected
from street traders in Meknes city. They were examined for the identification of
Enterococcus spp. using biochemical tests and 16S rRNA gene sequencing. The
antimicrobial susceptibility of the isolates was determined. Results: The results
showed that 11.3% (17/150) of samples were positive for the presence of
Enterococcus spp., of which 64.7% were identified as Enterococcus faecalis, 17.6%
as Enterococcus faecium, 11.8% as Enterococcus durans and 5.9% as Enterococcus
hirae. The antimicrobial susceptibility showed that all Enterococcus spp. were
resistant to ampicillin. The species E. faecalis, E. faecium, E. durans and E.
hirae were resistant to streptomycin, with percentages of 52.9% (9/17), 11.8%
(2/17), 11.8% (2/17), and 5.9% (1/17) respectively. All isolated strains of E.
faecalis and E. faecium were resistant to tetracycline. The multiple antibiotic
resistance index was elevated in the majority of Enterococcus spp., reaching
values higher than 0.5, indicating a risk for public health. Conclusion: This
study shows that the raw milk consumed by the population is contaminated with
strains of Enterococcus resistant to antibiotics used in breeding for
prophylactic purposes. This requires raising the awareness of those involved in
the production and marketing of milk, so as to take measures to apply good
hygienic practices and rationalize the use of zootechnical antibiotics.
PMID- 29951381
TI - Multidrug-resistant bacteria isolated from cell phones in five intensive care
units: Exploratory dispersion analysis.
AB - Introduction: Cell phones are susceptible to bacterial contamination. The aim of
this study was to characterize the bacterial isolates and to explore their
dispersion in five Intensive Care Units (ICUs) over the time. Methods: We
performed a secondary analysis of non-fermenting Gram-negative bacteria and Gram
positive cocci isolated from a 5-month observational cohort study developed among
health care workers' cell phones in five ICUs. Cell phones were sampled using a
swab every 15 days. Antimicrobial resistance was determined by the minimum
inhibitory concentration method. We constructed resistance phenotypes to group
the isolates according to species and antimicrobial resistance pattern to explore
dispersion through time. Results: A total of 35 P. aeruginosa, 16 Acinetobacter
spp., 30 S. aureus and 26 Enterococcus spp. were isolated from 491 phone samples.
Multidrug resistance was 2.9% for P. aeruginosa, 31.3% for Acinetobacter spp.,
46.7% for S. aureus and 80.8% for Enterococcus spp. The resistance to methicillin
in S. aureus and to vancomycin in Enterococcus spp. was 26.7% and 42.3%,
respectively. We did not observe distribution patterns or clusters over the time
for P. aeruginosa, Acinetobacter spp. and Enterococcus spp. isolates. All the S.
aureus isolates grouped into eight phenotypes. Interestingly, we observed S.
aureus isolates with the same phenotype in consecutive and separate sampling
dates in the same cell phone. Conclusion: Cell phones are contaminated with
highly harmful bacteria and potentially can maintain them for prolonged periods
of time. These devices could be considered as a potential source of nosocomial
infections in ICUs.
PMID- 29951382
TI - Community acquired Klebsiella pneumoniae meningitis: a case report.
AB - Introduction: Klebsiella pneumoniae meningitis is most commonly seen as a
nosocomial infection and in post-neurosurgical patients. Reports of community
acquired Klebsiella pneumoniae meningitis cases are rare in the United States.
The objective of this case report is to discuss an uncommon pathogen causing
meningitis, Klebsiella pneumoniae, its risk and prognostic factors and to
emphasize the importance of early recognition and appropriate antibiotic
treatment. Case report: We report a clinical case of adult community acquired
Klebsiella pneumoniae meningitis with recovery. A 54-year-old diabetic male
presented with two-week history of intermittent fevers, acute bilateral ear pain,
headache and unsteady gait. Broad spectrum antibiotics were initiated. Klebsiella
pneumoniae was isolated in the cerebrospinal fluid cultures. The patient
recovered with only mild hearing loss in his left ear. Conclusion: Our case
highlights the importance of suspecting Klebsiella pneumoniae in community
acquired meningitis.
PMID- 29951383
TI - Appropriate types of futures studies scenarios in health.
AB - Background: Scenario is the primary method in futures studies, and thus its
improper use can undermine the credibility and claims of the results. There are
many scenario types, and here we aimed at understanding whether these scenarios
are being used properly in the health field. Methods: In this study, a
combination method was used in 3 phases, and 8 + 2 steps were considered to
accommodate the needs of the health sector with capabilities of the main types of
scenarios. One of the appropriate methods of futures studies was used at each
step. Results: Scenario planning has evolved along with futures studies
paradigms. Trend-based scenarios, intuitive logic, and structural analysis
approaches have had the most use in futures scenarios and health section.
Quantitative techniques, which are close to the positivist paradigm, have been
most widely used; however, participatory methods of futures studies paradigm have
been used the least in the health sector. Conclusions: Health scenario writing in
its current state is targeting short- to medium- term futures and does not
respond to all requirements. Thus, other backup methods should also be
considered.
PMID- 29951384
TI - The Relationship between insulin variable number of tandem repeats (INS-VNTR) -23
A/T and cytotoxic Tlymphocyte associated protein-4 (CTLA-4) +49 A/G polymorphisms
with islet autoantibodies in persons with diabetes.
AB - Background: Both genetic and environmental factors are important in pathogenesis
of diabetes. Non HLA (Human Leukocyte Antigen) genes such as INS-VNTR and CTLA-4
in addition of HLA genes have influence on genetic susceptibility for diabetes
mellitus. In this study the association of +49 A/G CTLA-4 and -23 A/T INS-VNTR
polymorphisms with diabetes and their association with islet autoantibodies were
investigated. Methods: Thirty four autoantibody positive adult persons with
diabetes mellitus and 39 persons with Type 1diabetes mellitus (T1DM), 40
autoantibody negative Type 2 diabetes mellitus (T2DM) patients and 40 healthy
controls were studied using Polymerase Chain Reaction-Restriction Fragment Length
Polymorphism (PCR-RFLP) technique. Results: The frequencies of -23 A/T INS-VNTR
genotypes were not significantly different among study groups. It was shown that
the distribution of the +49A/G CTLA-4 allele and genotype frequencies did not
differ between T1DM patients, autoantibody positive adult patients and controls.
With increasing CTLA-4 G allele and GG/AG genotypes, the frequency of Glutamic
Acid Decarboxylase Autoantibody (GADA), Islet Cell Autoantibody (ICA) and Islet
Antigen 2 Antibody (IA2A) positive patients were increased. Conclusion: Our
results suggest that susceptibility allele A of -23A/T INS-VNTR does not have any
role in the pathogenesis of diabetes in our patients and susceptibility allele G
of +49 A/G CTLA-4 if not, has a small role in pathogenesis of diabetes in T1DM
and autoantibody positive adult patients and in spite of significant increase in
autoantibody negative T2DM group it does not have any role in disease
pathogenesis.
PMID- 29951385
TI - Foresight in health sciences using CLA method.
AB - Background: Development in health is not possible without progress of science.
Rapid changes in the various areas make the future health system more complex and
risky. Therefore, foresight of health sciences is very important. Methods: This
futures studies was conducted in 4 steps; also, literature and documents review,
statistics and information review, focus group discussions, working group, and
scenario planning were used. Cause level analysis was used for data analysis and
syntactic as main frameworks. Results: The findings in legal health sciences
documents revealed that the value system was not defined clearly and coherently
and that logical linkage among myths, discourse, and social structural layers was
ambiguous. In trend analysis, 24 trends were recognized; however, political and
economic streams were strong, independent, and uncertain factors which created 4
main scenarios although the social and environmental factors divided them into 16
subscenario tunnels. Postmodern discourse in probability scenarios will be
dominant and science will be understood as tools for generation of wealth.
University structure will be decentralized and transformed into similar R&D to
join the health industry, and our quantitative growth (articles, disciplines, and
students) in health sciences will decrease. Conclusion: If the current trends
(probability scenarios) continue, we will move to an undesirable situation. The
main challenge in this regard is the lack of a unique and dominant discourse in
health sciences based on the Islamic Republic of Iran doctrine. Therefore, in
this study, shifting the paradigm by a new approach and discipline in the health
sciences is suggested.
PMID- 29951386
TI - Speech intelligibility after repair of cleft lip and palate.
AB - Background: Intelligibility refers to understandability of speech; and lack of it
can negatively affect children's overall communication effectiveness. Children
with repaired cleft lip and/or cleft palate (CL/P) may experience poor speech
intelligibility. This study aimed at evaluating speech intelligibility in
children with repaired CL/P who had not been referred to speech-language
pathology clinics for early intervention. Methods: Sixty-four monolingual Persian
speaking children, 32 children with repaired CL/P, and 32 controls aged 3 to 5
years participated in this survey. Their speech intelligibility was evaluated
through the Persian Speech Intelligibility Test and was normalized on children 3
to 5 years. Each speech sample was heard by a speech and language pathologist
(SLP), as well as 2 nonprofessional listeners. Two objective measures of speech
intelligibility including Percentage of Consonants Correct (PCC) and Percentage
of Intelligible Words (PIW) were used in this research. Results: Children with
CL/P were significantly outperformed by their peers in PCC (p= 0.0001) and PIW
(p= 0.0001). More than half of the case group had compensatory errors and 40.6%
had obligatory errors. The PCC and the PIW were statistically different in
children with different rates of hyper nasality (p= 0.001). Conclusion: Speech
intelligibility of children with CL/P is impaired due to their articulation
disorders (obligatory and compensatory errors). This survey documents the
necessity for speech therapy for increasing speech intelligibility in this
population.
PMID- 29951387
TI - Efficiency measurement of health care organizations: What models are used?
AB - Background: Literature abounds with various techniques for efficiency measurement
of health care organizations (HCOs), which should be used cautiously and
appropriately. The present study aimed at discovering the rules regulating the
interplay among the number of inputs, outputs, and decision- making units (DMUs)
and identifying all methods used for the measurement of Iranian HCOs and
critically appraising all DEA studies on Iranian HCOs in their application of
such rules. Methods: The present study employed a systematic search of all
studies related to efficiency measurement of Iranian HCOs. A search was conducted
in different databases such as PubMed and Scopus between 2001 and 2015 to
identify the studies related to the measurement in health care. The retrieved
studies passed through a multi-stage (title, abstract, body) filtering process.
Data extraction table for each study was completed and included method, number of
inputs and outputs, DMUs, and their efficiency score. Results: Various methods
were found for efficiency measurement. Overall, 122 studies were retrieved, of
which 73 had exclusively employed DEA technique for measuring the efficiency of
HCOs in Iran, and 23 with hybrid models (including DEA). Only 6 studies had
explicitly used the rules of thumb. Conclusion: The number of inputs, outputs,
and DMUs should be cautiously selected in DEA like techniques, as their
proportionality can directly affect the discriminatory power of the technique.
The given literature seemed to be, to a large extent, unsuccessful in attending
to such proportionality. This study collected a list of key rules (of thumb) on
the interplay of inputs, outputs, and DMUs, which could be considered by most
researchers keen to apply DEA technique.
PMID- 29951388
TI - Lower thoracic disc herniation mimicking lower lumbar disk disease: A case
report.
AB - Thoracic disk herniation comprises 0.15% of all disk herniation and has various
and confusing manifestations. Among them, radicular pain down the leg could be
the rarest presentation, especially if it is the only complaint. On the other
hand, finding the relationship between clinical and paraclinical needs require
high index of suspension and it is demanding. A 34-year-old patient, who had a
history of intermittent back pain, with lower thoracic disk herniation presented
by acute leg sciatica-like pain, is reported. He suffered 3 weeks of acute back
pain prior to admission, which radiated down to buttock and leg, with a vague
left abdominal pain, whose clinical examination indicated a distal lumbar
problem. MRI showed T-12 L-1 disk herniation. Lower thoracic disc herniation can
compress lumbosacral roots immediately after exiting from cord thickening in the
lower thoracic area, so they can incite lower lumbar radiculopathy and cause
discordance between MRI findings and clinical presentation, suggesting a lumbar
problem, and this can lead to delayed diagnosis. However, the acute pain was
completely improved after open discectomy.
PMID- 29951389
TI - Effectiveness of trastuzumab as adjuvant therapy in patients with early stage
breast cancer: A systematic review and meta-analysis.
AB - Background: Trastuzumab in combination with chemotherapy has long been
established as a standard treatment for HER2-positive patients in early stage
breast cancer (BC). The present study aimed at assessing the effectiveness of
trastuzumab adjuvant therapy in early stage BC in overall survival (OS) and
disease-free survival (DFS). Methods: A systematic review and meta-analysis was
performed to evaluate the effectiveness of trastuzumab adjuvant therapy. PubMed,
Cochrane library, Scopus, Web of Science, and Embase databases were searched for
relevant RCTs from the beginning to February 2017. Quality assessment of studies
was conducted using the Cochrane Risk of Bias Tool. The desired outcomes were OS
and DFS. Results: A total of 1818 articles were identified first, however, only
11 studies were eligible to be included in this study. Our findings and meta
analysis results revealed that trastuzumab is effective in increasing OS (OS
hazard ratio: -0.286 +/- 0.049, 95%CI (-0.381, - 0.191)) and improving DFS (DFS
hazard ratio: -0.419+/- 0.077, 95%CI (-0.569, -0.269)). The most serious but
negligible side effect of trastuzumab is congestive heart failure. Conclusion:
Adding trastuzumab as adjuvant therapy in early stages of BC in HER2 positive
patients could increase OS and DFS of the patients effectively.
PMID- 29951390
TI - A Model for settlement of health insurance organizations' debt to health service
delivery institutions.
AB - Background: Sukuk is a type of financial instrument backed by balance sheet and
physical assets. This applied and descriptive study aimed at providing solutions
to the problems faced by insurance companies in the health sector. Methods: In
this study, we achieved operational models by reviewing the release nature and
mechanism of any of the securities and combining them. Results: According to the
model presented in this study, 2 problems could be solved: settling the past
debts and avoiding future debts. This model was deigned based on asset backed
securities. Conclusion: Utilizing financing instruments (such as Sukuk), creating
investment funds, and finding a solution to this problem, this study was
conducted in 2 aspects: (1) models that are settling old debts of the
organization, and (2) models that prevent debts in the future.
PMID- 29951391
TI - Essential managerial skills for financial and budgetary management in medical
universities: The top managers' perspective.
AB - Background: Achieving organizational objectives depends on the effectiveness of
administrators. However, managerial efficacy largely depends on the knowledge and
skills of managers. This study aimed at assessing the skills of financial and
budget management of the Ministry of Health from the perspective of resource
development assistants of universities of medical sciences nationwide. Methods:
This cross- sectional study was conducted in 2012. Study participants were
resource development assistants of universities of medical sciences in Iran. We
adopted simple random sampling method in locating participants. Data were
collected using pretested questionnaires and analyzed using descriptive
statistics and Mann-Whitney test (as a non-parametric test) and Friedman test.
Results: The highest mean recorded under financial management skills was
technical skills (3.58+/-0.50), followed by human skills (3.50+/-.048), and
perceptual skills (3.32+/-0.52). With regards to financial and budget management
and performance monitoring, the means of technical skills, as prioritized by
directors, was 3.72+/-0.71, followed by human skills (3.72+/-0.70), and
perceptual skills (3.66+/-0.75). A significant association was found between
perceptual skills of financial managers and budgeting and performance monitoring
managers (p= 0.014). Conclusion: Operational level managers, such as financial
and budgetary managers, need to acquire more technical skills. Therefore, we
support activities that promote technical skills and awareness of managers within
organizations, such as organizational training courses and distribution of
educational materials like brochures.
PMID- 29951392
TI - Assessment of length of stay in a general surgical unit using a zero-inflated
generalized Poisson regression.
AB - Background: The effective use of limited health care resources is of prime
importance. Assessing the length of stay (LOS) is especially important in
organizing hospital services and health system. This study was conducted to
identify predictors of LOS among patients who were admitted to a general surgical
unit. Methods: In this cross-sectional study, the sample included all patients
who were admitted to the general surgical unit of Shariati hospital in 2013 (n=
334). To determine the factors affecting LOS, Zero-inflated Poisson (ZIP), zero
inflated negative binomial (ZINB), and zero-inflated generalized Poisson (ZIGP)
regression models were fitted using R software, and then the best model was
selected. Results: Among all 334 patients, the mean (+/-SD) age of the patients
was 45.2 (+/-16.47) years and 220 (65.9%) of them were male. The results revealed
that based on ZIGP model, type of surgery (appendicitis, abdomen and its
contents, hemorrhoids, lung, and skin), type of insurance, comorbid diseases
(hypertension, heart disease, and hyperlipidemia), place of residence (local and
non-local), age, and number of tests had significant effects on the LOS of GS
patients. Conclusion: According to the Akaike information criterion (AIC) in each
fitted model, it was found that ZIGP regression model is more appropriate than
ZIP and ZINB regression models in assessing LOS in GS patients, especially due to
the presence of excess zeros and overdispersion in count data.
PMID- 29951393
TI - Effects of recruiting midwives into family physician program on the percentage of
low birth weight (LBW) infants in rural areas of Kurdistan.
AB - Background: LBW is an important factor that can affect infant mortality and
represents an index of economic and social development. It is expected that an
increase in the density of midwives attending family physician programs will lead
to a decrease in LBW in health centers. This study aimed to compare the
percentage of LBW infants before and after the implementation of the family
physician program in health centers with and without an increase in midwives
density. Methods: This cross-sectional study compared the percentage of LBW
infants before and after the implementation of family physician programs in rural
health centers with and without changes in midwives density in Kurdistan. In this
study, we included 668 mothers of 2-month-old children and administered
structured interviews in 2005 and 2013. Data were analyzed using the difference
indifferences and the Matchit statistical models. Results: The Matchit model
showed a significant average percentage increase 0.08 (0.006-0.17) in LBW infants
born between 2005 and 2013 in health centers where the density of midwives
increased compared with those where it remained unchanged. The difference-in
differences model showed that the odds ratio of LBW infants is increased by more
than twice among participants who had a history of caesarean section. Conclusion:
The results of this study showed that an increase in the density of midwives in a
family physician program did not have an impact on reducing the percentage of LBW
infants born between 2005 and 2013, in health centers where the density of
midwives augmented compared to those where it remained unaltered; it indicated
that the increase in the density of midwives alone was not efficient. On the
other hand, the results of our study show an increase in the risk of infants born
at a LBW due to caesarean section. It is recommended that obstetricians and
gynecologists must strictly control pregnancies and avoid unnecessary termination
of pregnancy.
PMID- 29951394
TI - Normal labor curve is affected by fetus gender: A cohort study.
AB - Background: Fetal male gender may affect the progression of labor and could be a
risk factor for labor arrest. This study was conducted to evaluate the effect of
fetus gender on labor curve. Methods: In this cohort study, 1550 singleton term
pregnant women in labor phase (either spontaneous or by induction) were enrolled.
Results of regular cervical examination, dilation, length of labor stages, mode
of delivery, and sex of the fetus, and birth weight were recorded for all
participants. Labor progression curve was compared between two sex groups with
independent t test and chi2 test. Results: Finally, 1527 women completed the
study (47.8% female and 52.1% male). Mean duration from beginning of the active
phase up to full dilatation, from 4 to 6 cm, 6 to 8 cm, and 8 to 10 cm
dilatations, were significantly longer in the male sex group compared to the
female (p?0.05). All durations were also significantly different when parity was
considered (p?0.05). We could not show fetal sex as an independent risk factor
for active phase arrest (OR Adjusted: 1.18, CI 95% 1.01:1.42). Conclusion: Active
phase stage was slower and longer in women who carried male fetuses compared to
those carrying female fetuses; however, fetal sex did not increase the risk of
active phase arrest.
PMID- 29951395
TI - Cost-effectiveness analysis of subcutaneous immunoglobulin replacement therapy in
Iranian patients with primary immunodeficiencies.
AB - Background: Economic evaluation of subcutaneous immunoglobulin therapy (SCIG) is
important, and it has recently been used for treatment of patients with primary
immunodeficiency (PID) diseases, and can improve allocation of resources in
health care systems. The present research aimed at providing an economic
assessment of SCIG and IVIG (intravenous immunoglobulin therapy) administration
in Iran. Methods: Data related to clinical effectiveness were obtained from a
meta-analysis. Economic analysis was performed taking into account the
perspective of health care providers. Incremental cost-effectiveness ratio (ICER)
was applied for economic evaluation of the 2 methods, and GDP per capita was
considered as a threshold. Results: The results of meta-analysis suggested a
higher effectiveness of SCIG compared to IVIG in serum immunoglobulin (Ig) levels
(SMD= 0.336) and adverse effects (OR= 0.497), while the cost of IVIG was higher
than SCIG ($1370 vs. $121). The ICER obtained in this paper ($2939 for adverse
effects and $4348 for serum Ig level) was less than the GDP per capita in Iran
($4,916.10), and thus SCIG is a more cost-effective therapy for PID patients.
Conclusion: Switching from IVIG to SCIG is cost-effective for PID patients and is
approved by the health care providers' points of view in this study.
PMID- 29951396
TI - Determination of Helicobacter pylori virulence-associated genes in duodenal ulcer
and gastric biopsies.
AB - Background:Helicobacter pylori (H. pylori or Hp) has been strongly associated
with the peptic ulcer diseases, chronic gastritis, ulcers, and gastric cancer.
Genes associated with pathogenicity have been designated for H. pylori, and some
of them appear to be related to more severe clinical consequences of the
infection. The present study was conducted to determine cagA, vacA, cagE, iceA1,
oipA, and iceA2 genes in H. pylori strains isolated from gastroduodenal patients,
who referred to Shariati hospital in Tehran, Iran. Methods: Gastric biopsy
specimens were collected during endoscopy from patients, who referred to the
Shariati hospital in Tehran, Iran during January and November 2015. After
isolation of H. pylori from the biopsy culture, genomic DNA was extracted and
subsequently used to identify H. pylori and virulence genes using specific
primers. Results: The isolation rate of H. pylori strains was 65.7% (169/257).
The frequency of cagA, vacA, cagE, iceA1, oipA, and iceA2 was 143 (% 84.6), 169
(100%), 131 (77.5%), 97 (57.3%), 89 (52.6%), and 72 (42.6%), respectively.
Conclusion: In this study, a significant difference was observed between
investigated genes and strains isolated from PUD and GC patients (p<0.05).
PMID- 29951397
TI - Leadership challenges in health care organizations: The case of Iranian
hospitals.
AB - Background: Effective leadership is a vital component of health care systems and
has an extensive range of functions in improving organizational effectiveness and
efficiency. This study aimed at exploring leadership challenges encountered by
leaders in Iranian hospitals. Methods: This qualitative study was conducted on a
purposeful sample of 27 members of hospital management team in Tehran using face
to-face semi-structured interviews and in-depth interviews. Thematic analysis was
used to analyze and report the data. Results: In this study, 5 main themes
emerged upon the challenges of leadership in health care organizations as follow:
organizational structure (complexity, centralization, and bureaucracy); human
resources (the number and distribution of human resources, staff empowerment, and
education, motivational mechanisms, and staff diversity); work nature
(sensitivity, stress and tension, customer diversity, and team- oriented);
leaders (knowledge and skills, appointment, superiors and colleagues, and time);
and context (regulations and programs, cultural issues, social issues, and
economic issues). Conclusion: The results of this study shed some light on the
leadership challenges in a culturally specific developing country. The results
also proved the importance of using educated leaders who are capable of
understanding, analyzing, and dealing with such complex challenges.
PMID- 29951398
TI - Survival analysis of thalassemia major patients using Cox, Gompertz proportional
hazard and Weibull accelerated failure time models.
AB - Background: Thalassemia major (TM) is a severe disease and the most common anemia
worldwide. The survival time of the disease and its risk factors are of
importance for physicians. The present study was conducted to apply the semi
parametric Cox PH model and use parametric proportional hazards (PH) and
accelerated failure time (AFT) models to identify the risk factors related to
survival of TM patients. Methods: The data of this historical cohort study (296
patients with TM) were collected during 1994 and 2013 in Zafar Clinic in Tehran.
Gompertz PH and Weibull AFT models were used for survival analysis (SA) of these
patients. Data analysis was performed using R3.2.2 software. Results: 153 (51.7%)
of patients were female; the mean (+/-SD) age of the patients was 29.11 (+/-0.47)
years. One-year survival rate for males and females was 0.963+/-0.007 and 0.973+/
0.013, respectively; and 3-year survival rate for males and females was 0.711+/
0.057 and 0.733+/-0.114, respectively. In the Gompertz model, birthplace and age
at onset of the disease were significant factors (p= 0.035, and p= 0.005) in
survival time. Also, in the Weibull model, birth place and age at onset of the
disease were significant factors (p= 0.013, and p= 0.008) in survival time. The
Akaike Information Criterion (AIC) for Weibull model was 158.51, which was lower
than other parametric models. Conclusion: According to the results, the Weibull
AFT model was found to be a better model for identifying the risk factors related
to survival of patients with TM disease. Informing parents, especially mothers
and paying attention to blood screening for early diagnosis may increase the
survival rate of patients.
PMID- 29951399
TI - Evaluation of age effects on doxorubicin-induced toxicity in mesenchymal stem
cells.
AB - Background: Doxorubicin, by aggregating in bone marrow, causes genotoxic effects,
and thus reduces the repair ability of cells. The present study was conducted as
an in vitro evaluation of age effects on the cytotoxicity induced by doxorubicin
in mesenchymal stem cells (MSCs). Methods: The MSCs of female BALB/c mice aged 1,
8, and 16 months were separated, characterized, and subsequently evaluated in
cellular growth media. After 24 hours, exposure of the MSCs of the 3 groups of
mice to doxorubicin (25, 50, 100, 200, 400, 800, 1200 nM) and cytotoxicity were
assessed, and the sublethal dose was determined using flow cytometry technique
and lactate dehydrogenase (LDH) release assay. Results: The IC50 values
determined by flow cytometry for the separated MSCs of 1 young, 8 middle- aged,
and 16 old mice were and respectively. Interestingly, the results of these 2
methods in determining cytotoxicity were in agreement, and a concentration of
approximately 25 nM was considered to be the shared sublethal dose for different
ages. Conclusion: The results indicated that MSCs of middle-aged mice were more
resistant to the toxic effects of the drug. Besides, MSCs separated from the old
mice were the most sensitive to chemotherapy and its side effects such as
disruptions of cell proliferation and viability. These disruptions can be
ascribed to the alteration of function and physiological processes with age.
Determining proper concentration of doxorubicin drug to destruct cancerous cells
based on age and individual sensitivity can minimize the amount of toxicity.
PMID- 29951400
TI - Evaluating ambulatory care training in Firoozgar hospital based on Iranian
national standards of undergraduate medical education.
AB - Background: In this study, ambulatory care training in Firoozgar hospital was
evaluated based on Iranian national standards of undergraduate medical education
related to ambulatory education using Baldrige Excellence Model. Moreover, some
suggestions were offered to promote education quality in the current condition of
ambulatory education in Firoozgar hospital and national standards using the gap
analysis method. Methods: This descriptive analytic study was a kind of
evaluation research performed using the standard check lists published by the
office of undergraduate medical education council. Data were collected through
surveying documents, interviewing, and observing the processes based on the
Baldrige Excellence Model. After confirming the validity and reliability of the
check lists, we evaluated the establishment level of the national standards of
undergraduate medical education in the clinics of this hospital in the 4
following domains: educational program, evaluation, training and research
resources, and faculty members. Data were analyzed according to the national
standards of undergraduate medical education related to ambulatory education and
the Baldrige table for scoring. Finally, the quality level of the current
condition was determined as very appropriate, appropriate, medium, weak, and very
weak. Results: In domains of educational program 62%, in evaluation 48%, in
training and research resources 46%, in faculty members 68%, and in overall
ratio, 56% of the standards were appropriate. Conclusion: The most successful
domains were educational program and faculty members, but evaluation and training
and research resources domains had a medium performance. Some domains and
indicators were determined as weak and their quality needed to be improved, so it
is suggested to provide the necessary facilities and improvements by attending to
the quality level of the national standards of ambulatory education.
PMID- 29951401
TI - Successful aging as a multidimensional concept: An integrative review.
AB - Background: Successful aging as an umbrella term with a large amount of
literature has emerged with a variety of meanings and dimensions in different
studies. This article aims at determining what dimensions contribute to
constructing the concept of successful aging. Methods: The method used in this
study is an integrative review of published literature related to successful
aging. This method includes both qualitative and quantitative studies. Data
searching was conducted during November and December 2014 and was then updated in
October 2015. First, 2543 articles were identified, and after the screening
phase, 76 articles were eligible for inclusion in the integrative review.
Results: The results specified 14 subcategories and 5 main categories of
successful aging: social well-being, psychological wellbeing, physical health,
spirituality and transcendence, and environment and economic security.
Conclusion: The present study provides a thorough understanding of successful
aging dimensions and proposes the importance of the multidimensional concept of
successful aging at the individual, interpersonal, and environmental levels for
future studies and policymaking on population aging.
PMID- 29951402
TI - The effectiveness of providing autologous transfusion education to operating room
staff.
PMID- 29951403
TI - Cloning, expression, and spectral analysis of mouse betatrophin.
AB - Background: Betatrophin, a novel secretory protein from liver and fatty tissues,
is believed to be involved in lipid and glucose metabolism. However, its precise
physiological role remains unclear. Here, we report the cloning, expression, and
purification steps of mouse betatrophin in a prokaryotic system, followed by its
structural analysis. Methods: Specific cloning primers were used to amplify the
coding sequence of mouse liver betatrophin. The product was cloned into pET28 and
expressed in E.coli BL21 (DE3) cells. The suitability of the refolding procedure
was assessed by determining secondary structures of the initial and refolded
proteins using circular dichroism spectroscopy. Results: The polymerase chain
reaction resulted in a 549 bp nucleotide sequence, encoding a 183 amino acid
polypeptide, with an apparent molecular weight of 21 kDa, which was expressed in
an inclusion body. Following an optimization and refolding procedure, the
recombinant protein was purified by anion exchange and metal affinity
chromatography. CD spectra revealed that the refolded protein has suitable
configuration. Conclusion: We believe that the produced betatrophin is suitable
for further biochemical studies on glucose and lipid metabolism.
PMID- 29951404
TI - Probiotics improve insulin resistance status in an experimental model of
Alzheimer's disease.
AB - Background: Nowadays, Alzheimer's disease (AD) is considered as Type 3 diabetes
in which insulin resistance is the common cause of both diseases. Disruption of
insulin signaling cascade and insulin resistance can induce AD; and central
insulin resistance causes systemic alterations in serum insulin, FBS levels, and
lipid profile. Studies have shown that probiotics (Lactobacillus and
Bifidobacterium species) can be used as a nutritional approach to improve these
metabolic changes. We assessed the probiotic effect (4 species of Lactobacillus
and Bifidobacterium) on insulin resistance biomarkers in an experimental model of
AD. Methods: A total of 60 rats were divided into 5 groups: (1) a control group
without surgical and dietary intervention; (2) a controlprobiotics group
receiving probiotics for 8 weeks, but not receiving any surgical intervention;
(3) a group receiving a sham operation in which PBS was injected intrahippocampus
but without dietary intervention; (4) an Alzheimer group for which Amyloid-beta
(Abeta) 1- 42 was injected intrahippocampus but without dietary intervention; (5)
and an Alzheimer-probiotics group for which Abeta1-42 was injected
intrahippocampus and given 2g probiotics for 8 weeks. The FBS levels and lipid
profile were measured by a calorimetric method, insulin levels were detected by
an ELISA kit, and HOMA-IR was calculated using a formula. ANOVA (one way analysis
of variance followed by Bonferroni comparisons post hoc) was used to compare all
the variables between groups. Results: Serum glucose, insulin levels, and HOMA-IR
index increased in the Alzheimer group compared to the control (p<0.001), while
probiotics decreased only insulin level and HOMA-IR index in AP group compared to
Alzheimer group (p<0.001). Also, TG levels increased in the Alzheimer group
(p<0.001), but no significant difference was detected between Alzheimer and
Alzheimerprobiotics group. Conclusion: It seems that probiotics play an effective
role in controlling glycemic status of Alzheimer's disease.
PMID- 29951405
TI - The frequency of bacterial contamination and diversity of drug resistance
patterns in devices and staff of endoscopy and colonoscopy units.
AB - Background: This study aimed at analyzing microbial contamination in medical
equipment, environment, and staff of a gastroenterology unit. Methods: Samples of
gastrointestinal imaging devices, the environment, and staff were collected using
standard swab-rinse technique and biochemical or molecular characteristics of the
isolates, their susceptibility to antibiotics, and similarity of the resistance
patterns were investigated. Results: Out of 107 samples, bacterial contamination
was detected in the hands of staff (54.1%), imaging devices (56.7%), and in the
environment (54.5%). While Pseudomonas spp. were detected only in the imaging
devices (13.5%), Bacillus spp. (32.4% and 31.5%), Enterococcus spp. (14.3% and
5.9%), Clostridium difficile (10.8% and 10.5%), and Staphylococcus epidermidis
(5.4% and 15.9%) were orderly the most common isolates from samples of the
imaging devices and the environment. Nearly, 40% of P. aeruginosa strains were
resistant to cefepime, while resistance to cephalosporins and beta-lactamase
inhibitor was detected in 33% and 75% of S. aureus strains, respectively.
Homology of resistance patterns was detected between the imaging devices and
hands of the staff. Conclusion: Our results proposed biofilm and spore forming
bacteria as main contaminants of imaging devices in this hospital. Homology of
the resistance patterns proposed involvement of staff in contamination of the
equipment.
PMID- 29951406
TI - Occupational health of Iranian farmworkers: A public health priority.
PMID- 29951407
TI - Stakeholders' network in Iranian health policy-making: A model for participatory
policy-making.
AB - Background: Stewardship, resource generation, financing, and providing services
are the 4 main functions in any health system. Using intelligence and common
sense in making policies and decisions is a subcomponent of the stewardship. The
present study aimed at designing a model that provides better access to the
stakeholders' wisdom. Methods: This was a qualitative study in which the data
were collected through reviewing documents and references, focused group
discussions with experts, and interviewing the stakeholders. The data were
analyzed and summed up as a conceptual framework. Then, the framework was
developed as a health policy-making stakeholders' network protocol, which
included the goal, structure, system process, procedures and standards,
management style, and resources. Results: The goal of establishing this network
was to facilitate and accelerate the access of policy-makers to the stakeholders'
opinions. Members of the network were divided into 2 groups of thematic experts
and administrative managers, as real or legal persons. Health policy issues were
categorized into 4 fields and defined in 18 subfields. The network was
established through forming a national secretariat, under the supervision of the
Minister of Health, with the presence of trained experts, and with an exclusive
budget. The stakeholders participated in the network both actively and passively.
The website and email were the first communication methods although there were
also other policy dialogue means, which were publicly declared through the annual
calendar. Stakeholders were motivated by being invited to meetings, keeping up
their intellectual ownership, and encouraging them. Conclusion: Strengthening the
health system stewardship depends on using common sense and information in
addition to vision formation and establishment of controlling mechanisms. The
stakeholders' network could help establish the 2 last components sustainably.
Annual evaluation of the network and its consolidation has also been suggested in
this study.
PMID- 29951408
TI - The effect of whole-body vibration training on the lower extremity muscles'
electromyographic activities in patients with knee osteoarthritis.
AB - Background: Whole-Body Vibration Training (WBVT) is a novel neuromuscular
training method that has been recently developed as a rehabilitation tool. The
purpose of this study was to determine whether WBVT is effective on
electromyographic activity of the muscles of the lower limbs in patients with
knee osteoarthritis. Methods: The study was designed as a single blinded
randomized clinical trial (IRCT201601171637N5), 45 patients with knee
osteoarthritis were randomly assigned to three groups; WBVT (n = 15) receiving 12
sessions vibration therapy, control group (n =15) doing two exercise in the home
and placebo (n =15) doing exercise like WBVT group on-off vibration system.
Electromyographic activities of vastus lateralis and vastus medialis,
semitendinosus, gastrocnemius and soleus were evaluated pre and post
intervention. The pairedsamples t-test and ANOVA were applied respectively to
determine the differences in each group and among the groups (P<=0.05). Results:
The RMS value of vastus medialis in semi squat position in placebo group
(p=0.024), vastus lateralis in SLR position in WBVT group (p=0.037), soleus in
knee flexion in WBVT group (p=0.018), semitendinosus in knee flexion in WBVT
group (p=0.007) and RMS response of Semitendinosus in ankle plantar flexion in
control group (p=0.047) were revealed significant differences between the pre-
and post- intervention. The ANOVA test confirmed the significant differences
between the studied groups according to the EMG activity of vastus medialis in
semi squat position (p=0.045), semitendinosus in semi squat position (p=0.046)
and in plantar flexion position (p=0.015) and also soleus in plantar flexion
position (p=0.003). Conclusions: The findings of this study showed the beneficial
effects of WBVT in the improvement of the muscles RMS values in the patients with
knee OA especially muscles' progression rates in a four-week period.
PMID- 29951409
TI - Explaining socioeconomic inequalities in illicit drug use disorders in Iran.
AB - Background: Drug use disorders are one of the major health problems in societies,
which cause physical, psychological, and social damages to individuals.
Socioeconomic status is often inversely associated with drug use disorders. The
present study aimed at determining the effect of socioeconomic inequality on the
prevalence of drug use disorders and identifying its determinants in Iran.
Methods: Data of 7886 individuals aged 15 to 64 years were collected from Iran
Mental Health Survey (IranMHS). Initially, the socioeconomic status of the
participants was determined by principal component analysis. Later, socioeconomic
inequality was measured using the concentration index, and the factors
influencing the gap between the high and low socioeconomic groups were identified
using the Oaxaca-Blinder Decomposition. Results: The concentration index for drug
use disorders in Iran was -0.29 (standard error= 0.06). The results of
decomposition technique revealed that 1.14% and 2.7% of the participants with
high and low socioeconomic status were affected by drug use disorders,
respectively. In addition, the gap between these 2 groups was found to be 1.65%.
Among the studied variables, occupation, marital status, and gender accounted for
the highest contribution to inequality, respectively. Conclusion: There is
inequality in the prevalence of drug use disorders in Iran; these disorders are
more common in lower socioeconomic group. Based on the findings, it is suggested
that improvement in the socioeconomic status of the households, especially for
males, the divorced or widowed individuals, and the unemployed may lead to a
reduction in inequality in drug use disorders.
PMID- 29951410
TI - Equity in the quality of hospital services in Iran.
AB - Background: Providing fair access to high-quality healthcare services is one of
the most important goals of health systems. This study was conducted between 2012
and 2013 to determine the level of equity in the quality of hospital services in
Iran. Methods: In this cross-sectional study, 1,003 patients were chosen from 100
hospitals in Iran with multi-stage random cluster sampling. Concentration index
was calculated to determine equity of healthcare quality from patients'
viewpoint. Furthermore, the equity of hospital services' quality was investigated
from experts' perspective by calculating Gini index based on the hospitals'
accreditation scores. Analyzing the related factors was done by logistic
regression. The significance level was set at alpha=0.05. Data were analyzed
using Excel v.2010, SPSS v.21, and Stata v.8. Results: There was a significant
inequity in the quality of hospital services in both patients' and experts' point
of view. In fact, concentration index (95% confidence interval) for the quality
of healthcare was significant, 0.128 (0.080, 0.176), indicating better quality of
services for those with higher economic status from patients' point of view.
Furthermore, Gini index (95% confidence interval) for hospitals' accreditation
scores was 0.166 (0.156, 0.176), meaning that there was inequity in hospital
services quality from experts' point of view. Conclusion: The significant
inequality observed in the quality of hospital care based on the economic status
of the patients highlights the necessity of the supportive policies aiming at
reduction of this condition.
PMID- 29951411
TI - The dairy fat paradox: Whole dairy products may be healthier than we thought.
PMID- 29951412
TI - Parental training and externalizing behaviors of children with severe hearing
loss.
AB - Background: Externalizing behavior in deaf children causes many psychological
problems for their parents. Aggression and rule breaking behaviors in children
with severe hearing loss may cause psychological problems in parents and in
managing children's behavior. Consequently, the present study aimed at
investigating the effect of parental behavioral training of mothers on reducing
the externalized behaviors (aggression and rule breaking behavior) of their 9- to
10- year old children with severe hearing loss. Methods: This was an experimental
study with pretest, posttest, and a control group. The research population
included all students with severe hearing loss and their mothers. Thus, 30
mothers whose children had the most severe hearing loss were selected as our main
sample among 80 mothers who had completed the Child Behavior Checklist. Then,
they were placed into the experimental (n=15) and control groups (n=15) after
being matched based on age, educational level, and socioeconomic status. The
research tool was Child Behavior Checklist-Persian Version. The parental behavior
training was provided for the experimental group in nine 90- minute sessions.
Results: The results of the present study indicated the effectiveness of
experimental treatment on decreasing the aggressive behaviors of children of
mothers in the experimental group compared to mothers of the control group
(p=0.001). Moreover, the results revealed a decrease in rule breaking behaviors
(p= 0.007) in children of mothers of the experimental group compared to mothers
of the control group. Conclusion: Parents' behavioral training is important in
decreasing the aggressive and offensive behaviors in children with severe hearing
loss who are at risk of behavioral problems. Furthermore, some research has
highlighted the necessity of such trainings for parents of these children. Thus,
the present study, emphasizing the importance of childhood problems, found that
mothers' behavioral training could prevent behavioral problems of school-aged
children with hearing loss and reduce the recurrence of such problems.
PMID- 29951413
TI - The duration effects of lumbar extensor muscle fatigue on postural control in
soccer players.
AB - Background: The ability to maintain body position in space is called postural
control. Muscular fatigue created after doing voluntary repeated contractions
impairs postural control. Thus, the present study was conducted to compare the
effects of fatigue of the lumbar extensor muscles and duration of these effects
on postural sway between soccer player and non-athlete participants. Methods: A
total of 15 male soccer players and 15 male non-athletes participated in this
cross- sectional study. Lumbar extensor fatigue is produced by a dynamometer and
maintains 60% of the maximum voluntary isometric contraction in standing
position. The mean velocity and the total area of the participants were evaluated
using force plate at baseline, immediately, 3, 6, and 9 minutes after fatigue and
compared between the 2 groups. Descriptive statistics, repeated measurement
ANOVA, and independent t test were used for data analysis. Results: The results
demonstrated that fatigue of the waist extensor muscles affects the postural sway
(p= 0.001). Also, the total area level was recovered earlier than the mean
velocity after fatigue. The results revealed that total area and velocity with
eyes closed decreased in the soccer player group compared with the non-athlete
group. Conclusion: Lumbar extensors fatigue significantly changed the mean
velocity and the total area in soccer players and non-athletes. Lumbar fatigue
had more effects on the total area than the mean velocity in the two groups.
PMID- 29951414
TI - Telemedicine: A systematic review of economic evaluations.
AB - Background: Telemedicine is an expanded term in health information technology
that comprises procedures for transmitting medical information electronically to
improve patients' health status. The objective of this research is to evaluate
the cost-effectiveness of telemedicine interventions in various specialty areas.
Methods: The Cochrane Library and Centre for Review and Dissemination were
searched up to February 2013 using Mesh. Studies that compared any kind of
telemedicine with any other routine care technique and used cost per health
utility unit's outcomes were included. Results: Twenty-one articles were
included. According to the included studies, it seems that using telemedicine in
cardiology can be effective and cost-effective enough but pre-hospital
telemedicine diagnostics program are likely to have little impact on acute
myocardial infarction fatality. In pulmonary, telemedicine can be a cost
effective strategy for delivering outpatient pulmonary care to rural populations
which have limited access to specialized services, but telemedicine is not cost-
effective in asthma and airways cancer. In ophthalmology, especially in the
diagnosis of diabetic retinopathy, the use of telemedicine is a cost-effective
tool. In dermatology, telemedicine is not cost-effective enough in comparison of
conventional cares. In other fields such as physical activity and diet, eating
disorder, tele-ICU, psychotherapy for depression and telemedicine on ships,
telemedicine can be used as a cost-effective tool for treatments or cares.
Conclusion: Most of the included studies confirmed that telemedicine is cost
effective for applying in major medical fields such as cardiology; but in
dermatology, papers could not confirm the positive capability of telemedicine.
PMID- 29951415
TI - Comparison of hematological parameters, iron levels, and oxidative stress in
women with and without breast cancer: A case- control study.
AB - Background: Iron is one of the nutrients that has recently received considerable
attention because of its dual role in the incidence of breast cancer. The present
study aimed at comparing hematological parameters, iron levels, and oxidative
stress in women with and without breast cancer. Methods: The participants in this
case-control study were 55 women, of whom 26 were new cases of breast cancer
(confirmed by biopsy) as the case, and 29 without cancer (confirmed by
mammography) as the control group. All participants underwent blood testing for
complete blood count (CBC (free iron, ferritin, total iron binding capacity) TIBC
(2, 2-diphenyl-1-picrylhydrazyl (DPPH), and Malondialdehyde (MDA). Results: The
mean+/-SD age of the participants was 44.25+/-9.82 years, and there was no
significant difference between groups. Also, no statistically significant
difference was found between the 2 groups in variables, except the mean
corpuscular volume of red cells (MCV), mean corpuscular hemoglobin concentration
(MCHC), and mean cell hemoglobin (MCH). The use of iron supplements was
significantly higher in the control than in the case group (p= 0. 01), with an
odds ratio of 0.19% (95% CI: 0.45-0.7). The mean serum DPPH was significantly
higher in the control than in the case group (p= 0. 006), but comparison of serum
MDA showed no significant difference between the 2 groups. Conclusion: Iron
deficiency anemia was greater in patients with breast cancer than in those
without it. Moreover, iron supplementation appears to have a protective effect
against breast cancer incidence. In addition, serum DPPH, as a total antioxidant
index, was significantly higher in the control group.
PMID- 29951416
TI - Economic burden of colorectal cancer in Iran in 2012.
AB - Background: Colorectal cancer is one of the most common cancers in Iran. However
little is known about the economic burden associated with this cancer in Iran.
The aim of this study was to estimate the economic burden of colorectal cancer in
Iran in the year 2012. Methods: We used the prevalence-based approach and
estimated direct and indirect costs of all colorectal cancer cases in 2012. To
estimate the total direct costs, we model the treatment process of colorectal
cancer patients in initial and continuing phase in Iran. Then the average cost of
each treatment in each phase was multiplied by the number of patients who
received the treatment in the country in 2012. We used the human capital method
to estimate the indirect costs. We extracted data from several sources, including
national cancer registry reports, hospital records, literature review,
occupational data, and interviews with experts. Results: The incidence and 5-year
prevalence of colorectal cancer in Iran in 2012 were 7,163 and 22,591 individuals
respectively. The economic burden of colorectal cancer in Iran was US$298,148,718
in 2012. Most of the cost (58%) was attributed to the mortality cost, and the
direct medical cost accounted for 32.14 percent of the estimated total cost. The
majority of the direct medical cost was associated with chemotherapy costs (50%).
Conclusion: The economic burden of colorectal cancer in Iran is substantial and
will increase in the future years.
PMID- 29951417
TI - Effect of educational intervention based on locus of control structure of
attribution theory on self-care behavior of patients with type II diabetes.
AB - Background: Different factors, such as personality and psychological
characteristics, are effective in the self-care and control of diabetes. This
study aimed at determining the effect of educational intervention based on locus
of control structure of attribution theory on the self-care behavior of patients
with type II diabetes. Methods: This was a quasi-experimental controlled study
performed on 180 patients in Babol Diabetes Association. The sampling method was
simple random sampling. Data collection tool was form C of standard questionnaire
in multidimensional health locus of control (MHLC) and summary of diabetes self
care activities (SDSCA). Based on the results obtained from the initial
completion of the questionnaires, educational intervention was designed as three
60-minute educational sessions using short lectures, question and answer, group
discussions, and consultation methods, as well as educational materials, such as
films, posters, and pamphlets. Intervention was only performed for the test
group. The questionnaires were filled out again 2 and 3 months after the
intervention. Results: Before the intervention, there was no significant
difference in the mean scores of self-care, internal, chance, and external locus
of control between the 2 groups. However, 2 to 3 months after the intervention,
the mean scores of self-care (p<0.001) and locus of control (p<0.001) increased
in the test group. Moreover, the mean score of chance (p<0.001) and external
(p<0.001) locus of control decreased significantly. Conclusion: Educational
intervention decreases the mean scores of chance and external locus of control
and increases the mean score of internal locus of control; as a result, it
improves self-care in patients with diabetes.
PMID- 29951418
TI - Digital games in health professions education: Advantages, disadvantages, and
game engagement factors.
AB - Background: The application of digital educational games in health professions
education is on expansion and game-based education usage is increasing. Methods:
Diverse databases were searched and the related papers were reviewed. Results:
Considering the growing popularity of educational games in medical education, we
attempted to classify their benefits, flaws, and engaging factors. Conclusion:
Advantages, disadvantages, and engagement factors of educational digital games
used for health professions education must be the focus of attention in designing
games for health professions discipline.
PMID- 29951419
TI - The effect of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on
the acoustic and prosodic features in patients with Parkinson's disease: A study
protocol for the first trial on Iranian patients.
AB - Background: The effect of subthalamic nucleus deep brain stimulation (STN-DBS) on
the voice features in Parkinson's disease (PD) is controversial. No study has
evaluated the voice features of PD underwent STN-DBS by the acoustic, perceptual,
and patientbased assessments comprehensively. Furthermore, there is no study to
investigate prosodic features before and after DBS in PD. The current study aimed
to assess the efficacy of STN-DBS on the voice and prosodic features by acoustic,
perceptual and self-reported evaluations in PD. Methods and Analysis: An
experimental prospective cohort pretest-posttest group has been designed to
survey patients with PD candidates for STN-DBS surgery. All participants will be
evaluated by a speech and language pathologist before and after surgery in four
different conditions as follow: pre-surgery: Medication On/ Medication Off; post
surgery: Stimulation On/ Stimulation Off. To compare pre-surgery and post-surgery
conditions paired- samples T Test or Wilcoxon signed-rank test will be used. A
95% confidence interval (p value of <0.05) will be considered to be statistically
significant. This study protocol is approved by the Ethical Committee of Teheran
University of Medical Sciences, and the results of the study will be published in
a peer-reviewed journal and presented at national congresses.
PMID- 29951420
TI - Application of media literacy education for changing attitudes about self
medication of slimming supplements.
AB - Background: Self-medication of slimming supplements has increased, and media
advertising has a role in this. The present study aimed at determining the effect
of media literacy educational intervention on attitudes about self-medication of
slimming supplements among the female students at dormitories of Iran University
of Medical Sciences. Methods: In this quasi-experimental study with a control
group, 98 students were selected by multistage cluster sampling method and were
randomly divided into 2 equal groups of test and control. The data collecting
instrument was a researcher-made questionnaire about media literacy and attitude
on self-medication of slimming pills. Based on the results obtained from the
early completion of the questionnaires, an appropriate educational intervention
was designed and implemented. Data were analyzed 1 and 3 months after the
intervention using the following statistical methods: repeated measurements,
Friedman test, Chi square, independent T-test and MannWhitney test. Results:
Before the intervention, the mean scores of attitude and dimensions of media
literacy were moderate in both groups, and there was no significant difference
between them. However, positive correlations were observed among attitude and
knowledge (r=0.99, p= 0.001), critical thinking (r= 0.61, p= 0.001), and analysis
(r= 0.37, p= 0.009) in the experimental group. The mean scores of attitudes and
dimensions of media literacy were found to be significant in both groups 1 and 3
months after the intervention (p<0.05). Conclusion: Media literacy education was
effective in promoting a positive attitude about slimming supplements.
PMID- 29951421
TI - Response shift in quality of life assessment among cancer patients: A study from
Iran.
AB - Background: During the course of disease, particularly of chronic diseases,
changes in internal standards cause certain changes in the estimation of quality
of life (QOL). These changes indicate the phenomenon of 'response shift'. The
present study aimed at assessing response shift in different scales of QOL in
Iranian cancer patients. Methods: To assess response shift through the 'then
test' approach, we asked 211 cancer patients to complete the EORTC QLQ-C30
questionnaire at pretest (at the beginning of the study), posttest (3 months
later), and then test (administered immediately after the posttest). Paired t
test and Cohen's effect size were used for comparison. Results: Response shift
was significant in all 4 scales under study, i.e. fatigue, pain, emotional
functioning, and general QOL (p<0.001). Fatigue, pain, and global QOL have
deteriorated significantly with then test approach and emotional function was
significantly improved. Conclusion: We observed a response shift in Iranian
cancer patients in our study. Thus, in light of the multifactorial nature of QOL
and the effect of the response shift bias on different aspects of QOL changes, it
is of utmost importance to keep this bias in mind when interpreting the results
and managing cancer patients' treatment regimens.
PMID- 29951422
TI - Immunophenotype evaluation of Non-Hodgkin's lymphomas.
AB - Background: Non-Hodgkin's lymphoma (NHLs) is known as a heterogeneous group of
malignant lymphoproliferative disorders. NHLs are classified into B cell and T
cell types. Immunophenotypical assessment of the biopsy specimens can help
diagnose NHLs. Methods: In this study, 77 patients with B cell and T cell
lymphoma were selected from Shahid Sadoghi hospital during 2010 to 2013.
Immunohistochemical method was used to detect biomarkers like CD2, CD3, CD20, and
CD45. Results: In this study, 67 patients (87.01 %) had B cell lymphoma.
Moreover, the most primary tissues in B cell group were lymph node and stomach,
followed by bone marrow and neck. Positive co-expression of CD45 and CD20 was
found in 61 patients (91.04%) with B cell lymphoma. However, 10 patients (12.98%)
had T cell lymphoma, and the most primary tissue in T cell lymphoma group was the
skin. Moreover, CD3 expression was seen in all patients with T cell lymphoma.
Conclusion: This study confirmed the main role of immunohistochemistry method in
classifying and diagnosing NHLs. Moreover, the difference in CD marker expression
and age in patients with B cell and T cell lymphoma, compared to other studies
may be due to geographic area and genetic and ethnic differences.
PMID- 29951423
TI - A Comparative study of four Persian versions of sleep questionnaires for
screening obstructive sleep apnea syndrome (OSAS).
AB - Background: Diagnosis of obstructive sleep apnea syndrome (OSAS) is valuable, but
it is time-consuming and expensive. Appropriate screening instruments help
clinicians select high-risk individuals for further investigations. In the
present study, we compared 4 popular instruments used in screening OSAS including
Berlin, STOP, STOP-BANG questionnaires, and Epworth Sleepiness Scale (ESS).
Methods: A total of 250 individuals, who referred to Sleep Laboratory of
Shoorideh Hospital (Tehran, Iran) for polysomnography during May 2015 to November
2015, were recruited for this cross-sectional study. In addition to taking
history and physical examination, 4 screening instruments including Berlin, STOP,
STOP-BANG questionnaires, and ESS were completed. Diagnosis of OSAS was
established using apnea-hypopnea index (AHI) in 3 categories of mild, moderate,
and severe. Results: Severe OSAS was diagnosed in 159 (63.6%), moderate OSAS in
43 (17.2%), and mild OSAS in 41 (16.4%) of the participants, moreover, AHI was
within normal range in the other 7 (2.8%). To diagnose OSAS with any severity,
Berlin questionnaire was a preferable instrument, with a sensitivity of 79.8% and
specificity of 71.4%, considering the cut-point value of 3.5. In addition, in
cases of severe OSAS, Berlin questionnaire showed superiority over other
instruments, with a sensitivity of 80.5% and specificity of 61.5% using the cut
point value of 3.5. Conclusion: None of the 4 instruments are ideal to predict
OSAS. However, considering the simplicity and availability of the instruments,
Berlin and STOP-BANG questionnaires had maximum diagnostic values that helped us
distinguish OSAS and severe OSAS, respectively.
PMID- 29951424
TI - A professional commitment scale for clinical nurses: A study protoco.
AB - Background: As the largest and most fundamental group targeted by programs
developed to improve quality of care, nurses should be the focus of attention in
the management of human resources in the field of health care. A review of
literature on this subject revealed the lack of scales designed for measuring
professional commitment in nurses. The present study was designed to develop a
scale to measure professional commitment in clinical nurses and examine its
psychometric properties. Methods: This study will develop a professional
commitment scale for clinical nurses within one qualitative and one quantitative
step. The first step of the study will entail a review of the literature on the
subject and interviews with clinical nurses so as to develop the categories and
the items. The second step, the quantitative step, will analyze the items
extracted in the qualitative step, determining the features of the topics and
factor structure of the scale. The initial scale will be completed by 300
clinical nurses. The correlation among the topics, the construct validity, and
reliability of the scale will also be examined in this step. Results and
Discussion: This study will develop an instrument that can measure professional
commitment in clinical nurses. Given the lack of instruments for measuring
professional commitment in clinical nurses, the findings of this study may be of
help to nursing managers, authorities, and the health system in general.
PMID- 29951425
TI - Oculomotor rehabilitation in children with dyslexia.
AB - Background: Dyslexia is the most common learning disorder. Visual and oculomotor
deficits in dyslexic children have been reported. The purpose of this study was
to measure oculomotor parameters and analyze the effect of oculomotor
rehabilitation strategies on dyslexia. Methods: Binocular eye movements were
recorded by oculomotor subtype of videonystagmography (VNG) testing on 30
children with dyslexia and 20 typical reader children (aged 8-12) in both
genders. Dyslexic children were diagnosed with DSM-V scale by experts in reading
disorder centers. We studied those children with developmental dyslexia, who had
deficits in eye movements recording. Dyslexic children were divided into 2 groups
of case and control. Oculomotor rehabilitation (including fixation, saccade, and
tracking training) was performed in case group for 1 hour, twice weekly for 8
weeks. Before the intervention, results of oculomotor tests were compared between
3 groups (healthy, case, and control). Then, to analyze the effect of the
intervention, results of oculomotor tests were compared between case and control
groups in pre- and post- intervention stage. Data were analyzed by independent
and paired samples t tests, ANOVA, and repeated measures tests in SPSS v. 21.
Results: There were significant differences in oculomotor characteristics of
dyslexic children in comparison with those reported in typical children.
Oculomotor rehabilitation intervention had a positive effect on improvement of
oculomotor responses and eye movements in dyslexic children. Moreover, there was
no statistically significant difference between dyslexic children and non
dyslexic children in oculomotor skills after the training. Conclusion: Our
results showed the positive effects of oculomotor rehabilitation on eye
movements. Primary oculomotor assessment in dyslexic children and early use of
oculomotor rehabilitation combined with other treatments are highly recommended.
PMID- 29951426
TI - Elder abuse: Screening in Iranian families.
AB - Background: The rate of elder abuse has been increasing worldwide. This study
aimed at identifying the group of elders susceptible to abuse and determining the
influential factors of elder abuse. Methods: A total of 683 elders, living in
rural and urban areas of Qazvin (Iran), participated in this cross- sectional
study that was conducted during September to December 2015. They were selected by
stratified multistage random sampling method and filled in a standard
questionnaire (H-S/EAST). Multiple logistic regression models were used for data
analysis in Microsoft SPSS v.18. Type 1 error was considered equal to 0.05.
Results: The average age of participants was 68.5+/-7.6. Also, the prevalence of
elder abuse in this study was 38.5 (95% CI: 3.34- 42.3). After eliminating the
confounders and applying multiple regression analysis, we found a significant
association between elder abuse and factors such as education level (OR= 2.003,
95% CI: 1.177-3.409), residence (OR= 3.53, 95% CI: 1.969-6.324), and age (OR=
0.963, 95% CI: 0.931-0.995). Conclusion: The results of this study indicated a
high prevalence of elder abuse in the studied population. By identifying high
risk individuals for elder abuse and planning to improve their quality of life,
we will be able to successfully overcome this issue.
PMID- 29951427
TI - Important considerations in calculating and reporting of sample size in
randomized controlled trials.
AB - Background: The calculation of the sample size is one of the most important steps
in designing a randomized controlled trial. The purpose of this study is drawing
the attention of researchers to the importance of calculating and reporting the
sample size in randomized controlled trials. Methods: We reviewed related
literature and guidelines and discussed some important issues in sample size
calculation and reporting in randomized controlled trials. Conclusion: The
calculation of the sample size is one of the most important steps in designing a
randomized controlled trial. According to the CONSORT (Consolidated Standards of
Reporting Trials) guideline and other standard guidelines for designing and
reporting of RCTs, sample size calculations should be reported and justified in
all published RCTs. Because sample size calculations are prone to bias and
because of the high ethical and financial costs related to conducting an RCT, we
recommend involving a biostatistician at the designing stage of the study and to
ask for statistical advice for sample size calculations.
PMID- 29951428
TI - Influence of MTHFR gene variations on perceived stress modification: Preliminary
results of NURSE study.
AB - Background: High level of perceived stress in nurses is due to a genetic
predisposition and environmental stressors. The aim of NURSE (Nursing
Unacquainted Related Stress Etiologies) study was to investigate the association
of C677T MTHFR gene polymorphism and stress perception among nurses. Methods: In
this comprehensive study, 216 female nurses were recruited. Perceived stress was
assessed using the Cohen Perceived Stress Scale (PSS). Genomic DNA was extracted
from peripheral blood, and MTHFR genotype was detected by the polymerase chain
reaction. Results: MTHFR C677T genotype analysis revealed that half of the
participants had normal C/C genotype, and the remaining half presented higher
frequencies of C/T genotype (39.8%) compared to T/T genotype (10.2%). The mean+/
SD stress score in morning shift, night shift, and rotation was 15.39+/-4.75,
15.92+/-4.94, and 15.83+/-5.61, respectively (p= 0.7). Perceived stress score was
more in highly educated group but it was not significant (p= 0.2). Distribution
of different MTHFR genotypes in diverse groups revealed that in groups with more
stress score, the frequency of heterozygote (C/T) and homozygote (T/T) genotypes
increased. Data revealed that in low stress category, 87% of the participants had
a normal genotype. However, in high stress category, 71.3% of the participants
had a normal genotype. Conclusion: MTHFR genotype, independent of folate
availability and probable confounding parameters, might be a potential risk
factor of perceived stress among nurses.
PMID- 29951429
TI - Psychometric properties of the Urdu version of the World Health Organization's
quality of life questionnaire (WHOQOL-BREF).
AB - Background: The present study was conducted to translate and validate the World
Health Organization's Quality-of-Life Scale - BREF into local language of
Pakistan. Methods: A forward- backward translation procedure was followed to
develop the Pakistani version of the questionnaire. Through a multi- stage
clustered sampling technique, a sample of individuals aged 18 years and above
completed the questionnaire in Abbottabad district, Pakistan. Psychometric
properties of the instrument including reliability (internal consistency and test
retest analysis), validity (known group comparison and items' correlation) and
their domains were assessed. Satisfactory results were also shown in the
correlation matrix in all domains. Results: A total of 2060 participants were
recruited in this study. Participants' mean age was 35.51 (SD= 14.31) years in
healthy individuals and 39.29 (SD= 14.31) years in diseased individuals. The
internal consistency of the WHOQOL-BREF (Pakistani Version) was 0.86. Moreover,
the physical, psychological, and environmental domains had acceptable reliability
(alpha= 0.78, 0.75, and 0.73, respectively), but reliability was low (alpha=
0.56) in the social domain. Reproducibility of the WHOQOL-BREF was as follows:
ICC range: 0.72-0.92 at 2-week retest interval. After performing comparison
analysis, the results indicated that the questionnaire significantly segregated
the study groups in all QoL domains, except for social relationship. Conclusion:
The study provided strong exploratory evidence for the reliability and validity
of the WHOQOL-BREF for use in Pakistan. However, more exploration is needed to
improve the reliability results in the social domain.
PMID- 29951430
TI - Depression among Iranian nurses: A systematic review and meta-analysis.
AB - Background: Depression is one of the most commonly diagnosed mental disorders.
Nurses and other hospital service providers are a group at high risk for
developing depression. Thus, knowing the prevalence of depression among nurses
can help the health care decisionmakers to plan ad hoc prevention programs to
control depression in this group. This study was conducted to quantitatively
assess the prevalence of depression in nurses by performing a systematic review
and meta-analysis. Methods: ISI/Web of Science (WoS), PubMed/MEDLINE via Ovid,
PsychInfo, and Embase, as well as Iranian databases such as Irandoc, SID, and
Magiran were searched from January 2000 to March 2017. To calculate the pooled
prevalence rate, the random effects model based on the DerSimonian-Laird approach
was used. I2 and the Q tests were used to examine heterogeneity among studies. To
investigate the causes and sources of heterogeneity, the impact of such variables
as quality, sample size, geographic region, and criteria used to diagnose
depression was analyzed performing subgroup analyses. The quality of reviewed
studies was assessed according to the 22-item STROBE checklist. Sensitivity
analysis was performed to investigate the stability and robustness of the
obtained results. All data were analyzed using the "meta" package included in the
R Software Version 3.4.0. Results: A total of 30 studies were retained in the
current investigation. The overall prevalence of depression was 22% [95%CI 19-
27] among nurses, with a high statistically significant heterogeneity (I2= 94%
and Q-test= 479.87). Conclusion: This rate was higher than the prevalence of
depression among the general population in Iran. Presence of happy nurses with
good mental state at hospitals is essential for promoting the care provided to
patients.
PMID- 29951431
TI - Theory-based interventions in STIs/HIV Prevention: A systematic review of the
literature in Iran.
AB - Background: Various theory-based interventions (TBIs) have been done to prevent
STI/HIV. The current study aimed at reviewing the TBIs for STI/HIV prevention in
Iran. Methods: We systematically searched 6 English and Persian electronic
databases to identify TBIs conducted for STI/HIV prevention in Iran. General
searches were conducted using PubMed MeSH terms. Articles were included if they
were interventional and conducted using models and theories, aimed at reducing
the risk of STIs, were quasi-experimental or experimental, and if their full text
was available. Results: Overall, 1042 studies were found. Finally, 13 original
studies met our inclusion criteria. The findings indicated that HBM and TPB were
the most frequently used theory/models. High school students and drug abusers
were the most common target groups in the included studies. Conclusion: The
results revealed that the majority of the conducted TBIs contained a
methodological weakness. Conducting randomized controlled trials is needed to
evaluate the effectiveness of the TBIs.
PMID- 29951432
TI - The effects of group blogging on the attitude towards virtual education in
nursing students.
AB - Background: Virtual education refers to a variety of teaching-learning methods
that are implemented and supported electronically. The present study was
conducted to determine the effects of group blogging on the attitude of nursing
students towards virtual education. Methods: This was a quasi-experimental
pretest-posttest study in which all fifth-semester nursing students (n=25) were
selected and asked to design educational blogs on nursing of respiratory
diseases. Attitudes of the participants towards virtual education were measured
before and after the intervention. Results: Pretest and posttest mean+/-SD were
2.98+/-1.03 and 3.46+/-0.68, respectively, showing a significant difference
(p<0.05). There were significant differences before and after the intervention in
the 2 subscales of importance of virtual education and interest in using virtual
environment (p<0.05). On the other hand, there was no significant difference in
the anxiety of using virtual environment before and after the intervention.
Conclusion: In general, the results revealed that blogging by nursing students
could improve students' attitudes towards virtual education.
PMID- 29951433
TI - Prevalence and predictors of dysphagia in Iranian patients with multiple
sclerosis.
AB - Background: Dysphagia is frequently observed in patients with multiple sclerosis
(MS). Dysphagia and its complications are common causes of morbidity and
mortality in final stages of MS disease. This study aimed at determining the
prevalence of dysphagia in Iranian patients with MS and identifying predictors
associated with dysphagia. Methods: A total of 230 MS patients were enrolled in
this cross-sectional study. Dysphagia was evaluated using Mann Assessment of
Swallowing Ability (MASA). Demographic characteristics (age and gender), duration
of the disease, disease course, and Expanded Disability Status Scale (EDSS) were
recorded for all participants. Results: In total, dysphagia was found in 85
participants (37%) with mild to severe dysphagia (mild 50.6%; moderate 29.4%; and
severe 20%). The logistic regression model demonstrated that disability status in
EDSS (OR= 2.1; 95% CI 0.5-1.2) and disease duration (OR= 2.3; 95% CI 0.4-1.1)
predicts a high risk for dysphagia in MS patients. Conclusion: Dysphagia is
prevalent in Iranian patients with MS. Disability level and disease duration are
significant predictors of dysphagia after MS.
PMID- 29951435
TI - No molecular evidence of Hepatitis E infection among patients with HIV in Iran.
PMID- 29951436
TI - Association of p53 codon 72 Arg>Pro polymorphism and risk of cancer in Iranian
population: A systematic review and meta-analysis.
AB - Background: Different studies have investigated the association between p53 codon
72 Arg>Pro polymorphism and cancer risk. Because of the lack of consensus of the
results in individual studies, we conducted this meta-analysis by pooling all
currently available case-control studies to estimate the effect of p53 codon 72
Arg/Pro polymorphism on cancer susceptibility in Iranian population. Methods: A
comprehensive search was undertaken and primary data from all peer-reviewed
journals indexed in PubMed, Google Scholar, Scopus, Magiran, Scientific
Information Databank (SID), Iran Medex, and CAB abstract electronic were used to
conduct this meta-analysis. We considered some exclusion and inclusion criteria
to select the articles. Statistical heterogeneity was explored using the I
square. Publication bias was assessed graphically and statistically by Begg's
funnel plot and Egger test. All statistical analyses were performed using
StatsDirect software and a two- tailed test. P-value less than 0.05 was
considered statistically significant for any test. Results: Our dataset, which
included 35 case-control studies, consisted of 2426 cancer cases and 2928
controls. Pooled OR and 95%CI indicated that codon 72 Arg>Pro polymorphism was
not associated with odds of developing cancer among Iranian population in the
dominant model (Pro/Pro+Arg/Pro vs. Arg/Arg: OR= 0.96, 95%CI= 0.74 to 1.24 chi2=
0.06, p= 0.8). Moreover, no significant association was detected in variant
allele (Pro vs Arg: OR= 1.075, 95%CI= 0.91 to 1.25), homozygous (Pro/Pro vs
Arg/Arg: OR=0.911 95%CI= 0.66 to 1.25), and heterozygous (Arg/Pro vs Arg/Arg: OR=
0.84, 95%CI= 0.7 to 1). Conclusion: Our study revealed that p53 codon 72 Arg>Pro
polymorphism was not associated with overall cancer odds in Iranian population.
PMID- 29951437
TI - The effect of low-frequency repetitive transcranial magnetic stimulation (rTMS)
on the treatment of aphasia caused by cerebrovascular accident (CVA).
AB - Background: Aphasia is a common outcome of Cerebrovascular Accident (CVA) in
which clinical interventions have limited effectiveness. Some evidence suggests
that noninvasive stimulation of the brain can have beneficial effects in the
treatment of CVA induced aphasia. In patients with motor aphasia, repetitive
Transcranial Magnetic Stimulation (rTMS) is used to facilitate long-term
improvement in speech ability. Since identifying effective methods for treating
CVA induced aphasia can be very important in subsequent decision-making and
treatment interventions, the objective of this study was to evaluate the effect
of low-frequency TMS in Broca's area in the right hemisphere on the treatment of
CVA induced motor aphasia. Methods: This clinical trial enrolled 24 patients with
a clinical diagnosis of motor aphasia caused by CVA using convenient sampling. In
this study, the effect of stimulation of Broca's area in the right hemisphere was
examined by low-frequency rTMS (one Hz) on aphasia caused by CVA. To conduct
verbal fluency test in patients, their correct responses to the selected images
before and after rTMS during a certain time were recorded and compared by non
parametric Wilcoxon test using SPSS16 and the significance level was considered
<0.05. Registration ID of this research in IRCT is IRCT2014052417814N1. Results:
The study findings suggested a significant difference between Wilcoxon test
results of patients before and after rTMS (z= -4.401), and it was found that
using low-frequency rTMS in the right hemisphere was effective on improving
dysarthria in the study population with 95 percent confidence interval (p<0.001).
Conclusion: According to the findings, low-frequency rTMS has the potential to be
considered as a treatment for patients with nonfluent aphasia caused by CVA.
PMID- 29951434
TI - Polyphenols and their effects on diabetes management: A review.
AB - Background: Type 2 diabetes is a growing public health problem and is associated
with increased morbidity and mortality. The worldwide prevalence of type 2
diabetes is rising. Polyphenols, such as flavonoids, phenolic acid, and stilbens,
are a large and heterogeneous group of phytochemicals in plant-based foods. In
this review, we aimed at assessing the studies on polyphenols and diabetes
management. Methods: A literature search in the PubMed, EMBASE, Scopus, and ISI
Web of Science databases was conducted to identify relevant studies published
from 1986 to Jan 2017. Results: Several animal models and a limited number of
human studies have revealed that polyphenols decrease hyperglycemia and improve
acute insulin secretion and insulin sensitivity. The possible mechanisms include
decrease in glucose absorption in the intestine, inhibition of carbohydrates
digestion, stimulation of insulin secretion, modulation of glucose release from
the liver, activation of insulin receptors and glucose uptake in insulin
sensitive tissues, modulation of intracellular signaling pathways, and gene
expression. Conclusion: Growing evidence indicates that various dietary
polyphenols may influence blood glucose at different levels and may also help
control and prevent diabetes complication. However, we still need more clinical
trials to determine the effects of polyphenols- rich foods, their effective dose,
and mechanisms of their effects in managing diabetes.
PMID- 29951438
TI - Is household food insecurity a determinant of weight status in patients with type
2 diabetes in rural areas?
AB - Background: There is mixed evidence about food insecurity and overweight/obesity
coexisting, however it is unclear about association between food insecurity and
weight status in people with type 2 diabetes. Therefore, the aim of this study
was to evaluate the relationship between food insecurity and weight status in
individuals with type 2 diabetes in rural areas in Iran. Methods: 1847 patients
with type 2 diabetes who were residence in rural areas completed Household Food
Security Scale (six-item short questionnaire). Logistic regression model was
applied to assess the independent effect of food insecurity on weight status.
Results: Mean age of the study population was 62.6+/-11.8 years, and the majority
of them were female (70.4%). Most of the study population (70.4%) had unhealthy
weight status. Food insecurity affected more than 46% (n=852) of the households
of the study population. According to weight status, more than 40% (n=565) of
overweight and obese subjects and 60% (n=18) of underweight subjects lived in
households with food insecurity. The results of multiple logistic regression
model showed that food insecurity was not an independent significant predictor of
overweight or obesity in patients with type 2 diabetes. However, low food
security (LFS) was an independent significant predictor for underweight in
patients with type 2 diabetes (OR=2.35, P=0.041). Conclusion: It is concluded
that food insecurity was frequent in all levels of weight status of patients with
type 2 diabetes in rural regions. However this association observed in
underweight individuals but there was no significant overall relationship between
household food insecurity and in overweight and obesity in this group of
patients.
PMID- 29951439
TI - Reduction and elimination solutions of informal payment in Iran's health system.
AB - Background: Informal payments can cause delayed access to health care services,
forcing people to sell their properties for cost of treatment; and as a result,
they lose trust in the health system. Considering the importance of this issue,
this study was conducted in 2016 to identify solutions to reduce and eliminate
informal payments in Iran's health system. Methods: Initially, solutions to
reduce informal payments were extracted by reviewing resources and searching
Persian and Englishlanguage databases including Science direct, PubMed, Scopus,
Medline, ISC, Magiran, SID using the following keywords: informal payments, under
the table payment, bribes, gratitude payment, and informal payments/fees. Then,
Iranian context specific solutions were obtained by performing semi-structured
interviews with 19 individuals, who were aware of the problem. Next, the
identified strategies were confirmed using Delphi technique and with the
participation of 50 experts. Results: Various solutions were identified and
confirmed to reduce or eliminate informal payments in Iran's health system, which
are divisible in different economical fields, such as payments to providers based
on performance, religious leaders' fatwa (sociocultural), disclosing the
offenders' names (legal-political), and using family doctor system (structural).
Conclusion: The proposed solutions can be used by policymakers and managers in
the health sector to manage informal payments. Careful identification of health
care providers and recipients' motivations and needs can be effective in
recognizing and eliminating this phenomenon.
PMID- 29951440
TI - A comparison between pregnancy outcome in women in 15 to 19 and 20 to 35 years
age group.
AB - Background: Pregnancy is one of the most important periods of a woman's life and
is influenced by many different factors. For years, it was assumed that teenage
pregnancy can cause poor pregnancy outcome. The purpose of this study was to
compare some pregnancy complications between 2 groups of 15 to 19 and 20 to 35
year- old primigravida pregnant women Methods: This was a cross- sectional study
conducted on the data sheets of primigravida women who delivered their babies in
a teaching hospital. A total of 3040 eligible women entered the study; of them,
280 (9.3%) were in the 15 to 19 years age group and 2756 in the 20 to 35 years
age group. The 2 groups were compared for preeclampsia, PROM, preterm birth, SGA,
placental abruption, and placenta previa. A logistic regression model was used
for data analysis. Results: The women of the 2 groups significantly differed in
BMI and socioeconomic background. The rate of preeclampsia (p=0.008), PROM
(p=0.002), and preterm delivery (p=0.001) were less in the 15 to 19 years age
group. The rate of placental abruption, placenta previa, IUFD, and SGA was not
significantly different between the 2 groups. After multivariate regression
analysis, preeclampsia (adjusted odd ratio= 2.157; 95% CI= 1.38- 4.21) and
preterm delivery (adjusted odd ratio= 2.443; 95% CI= 1.78- 5.13) were found to be
higher in the 20 to 35 years group. Conclusion: The risk of poor pregnancy
outcome is not higher in teenage pregnancies compared to pregnancies in the 20 to
35 years age group if confounding factors, including socioeconomic factors, are
carefully controlled.
PMID- 29951441
TI - Alzheimer 's Disease: Possible Mechanisms Behind Neurohormesis Induced by
Exposure to Low Doses of Ionizing Radiation.
AB - In 2016, scientists reported that human exposure to low doses of ionizing
radiation (CT scans of the brain) might relieve symptoms of both Alzheimer's
disease (AD) and Parkinson disease (PD). The findings were unbelievable for those
who were not familiar with neurohormesis. X-ray stimulation of the patient's
adaptive protection systems against neurodegenerative diseases was the mechanism
proposed by those authors. Now, some more recent studies performed in the field
of neurobiological research confirm that low levels of stress can produce
protective responses against the pathogenic processes. This paper outlines
possible protective consequences of LDR in preventing the pathogenesis of AD
through mechanisms such as restoring the myelin sheath and preventing
neurodegeneration caused by oxidative stress. Focal demyelination is frequently
reported in the proximity of beta-amyloid plaques within neocortex. Extracellular
accumulation of amyloid is among well-characterized pathological changes in AD.
It should be noted that LDR has been shown to contribute to the regeneration and
functional recovery after transverse peripheral nerve injury (through inducing
increased production of VEGF and GAP-43), which advances both the axonal
regeneration and myelination. Another mechanism which is possibly involved is
preventing neurodegeneration caused by oxidative stress. While high doses can
induce reactive oxygen species (ROS) formation, oxidative stress and neuro
inflammation, substantial evidence now indicates that LDR can mitigate tissue
damage through antioxidant defenses. Although adult neurogenesis has been
reported to be beneficial for the regeneration of nervous system, some studies
demonstrate that neurogenesis increases in AD brains. In spite of these reports,
cellular therapy is introduced as a promising strategy for AD, and hence, LDR can
affect the proliferation and differentiation of neural stem cells. Although such
mechanisms are not fully known yet, it is hoped that this paper would foster
further investigation into the mechanisms of this phenomenon, which accordingly
improves human health.
PMID- 29951442
TI - Benchmarking of Siemens Linac in Electron Modes: 8-14 MeV Electron Beams.
AB - Background: Radiation therapy using electron beams is a promising method due to
its physical dose distribution. Monte Carlo (MC) code is the best and most
accurate technique for forespeaking the distribution of dose in radiation
treatment of patients. Material and Methods: We report an MC simulation of a
linac head and depth dose on central axis, along with profile calculations. The
purpose of the present research is to carefully analyze the application of MC
methods for the calculation of dosimetric parameters for electron beams with
energies of 8-14 MeV at a Siemens Primus linac. The principal components of the
linac head were simulated using MCNPX code for different applicators. Results:
The consequences of measurements and simulations revealed a good agreement. Gamma
index values were below 1 for most points, for all energy values and all
applicators in percent depth dose and dose profile computations. A number of
states exhibited rather large gamma indices; these points were located at the
tail of the percent depth dose graph; these points were less used in in
radiotherapy. In the dose profile graph, gamma indices of most parts were below
1. The discrepancies between the simulation results and measurements in terms of
Zmax, R90, R80 and R50 were insignificant. The results of Monte Carlo simulations
showed a good agreement with the measurements. Conclusion: The software can be
used for simulating electron modes of a Siemens Primus linac when direct
experimental measurements are not feasible.
PMID- 29951443
TI - An Aptamer-based Biosensor for Troponin I Detection in Diagnosis of Myocardial
Infarction.
AB - Background: Acute myocardial infarction (MI) accounts for one third of deaths.
Cardiac troponin I (TnI) is a reliable biomarker of cardiac muscle tissue injury
and is employed in the early diagnosis of MI. Objective: In this study, a
molecular method is introduced to early diagnosis of MI by rapid detection of
TnI. Materials and Methods: The detection method was based on electrochemical
aptasensing, being developed using different methods and evaluation steps. A gold
electrode was used as a transducer to successful immobilize 76base aptamer to
fabricate a TnI biosensor. Results: The designed aptasensor could detect TnI in a
range of 0.03 to 2.0 ng mL-1 without using any label, pre-concentration or
amplification steps. The limit of detection was attained as 10 pg mL-1 without
significant trouble of interfering species. The TnI biosensor demonestrated a
stable, regenerative and reproducible function. 89 human samples were used to
evaluate the performance of the TnI biosensor, and it represented 100% and 81%,
diagnostic sensitivity and specificity, respectively. Conclusion: This aptasensor
may be used as an applicable tool in the future of early medical diagnosis of MI.
PMID- 29951444
TI - Evaluation of Blood Parameters Alteration Following Low-dose Radiation Induced by
Myocardial Perfusion Imaging.
AB - Introduction: With increasing the usage of myocardial perfusion imaging (MPI) for
the diagnosis of ischemic heart disease, we aimed to evaluate the side effects of
low-dose radiation induced by this technique on blood elements, especially
proteins and liver function factors. Material and Methods: 40 eligible patients
(Mean age: 54.62+/-10.35, 22 female and 18 male), who had referred to the nuclear
medicine department for MPI from May till August 2014, were enrolled in the
study. A blood sample was taken from each patient just before and 24 hours after
the injection of 740Mbq of Tecnetium-99m Methoxy isobutyl isonitrile (99mTc-MIBI)
in the rest phase of the MPI in a reference medical laboratory; blood tests
included total protein (TP), albumin (Alb), globulin (Glo), aspartate
aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP),
direct bilirubin (D.Bili), total bilirubin (T.Bili), serum iron (SI), total iron
bounding capacity (TIBC), Albumin globulin ratioA/G ratio), and complete blood
count (CBC). Results: Injection of 740Mbq99mTc-MIBI caused a significant increase
in serum levels of AST (p= 0.001), ALT (p= 0.001), SI (p= 0.030), TIBC (p= 0.003)
and A/G Ratio (p= 0.020). However, following radiotracer injection, a significant
decrease was noted in the serum levels of TP (p= 0.002), Alb (p= 0.014), Glo(p=
0.002), ALP (p= 0.001), D.Bili (p= 0.003) and T.Bili (p= 0.000). Conclusion: Due
to increased usage of MPI, our data highlights the importance of monitoring the
clinical and paraclinical effects of the procedure on vital organs and
physiological pathways to reduce their adverse effects.
PMID- 29951445
TI - Effect of Microwave Wi-Fi Radiation at Frequency of 2.4 GHz on Epileptic Behavior
of Rats.
AB - Background: Electromagnetic fields (EMF) with different intensities are widely
used at home, offices and public places.Today, there is a growing global concern
about the effects of human exposure to EMFs. Epilepsy is one of the most common
chronic neurological diseases, affecting 50 million people of all ages worldwide.
We aimed to investigate the effect of exposure to Wi-Fi radiation on epileptic
behavior of rats. Materials and Methods: 147 male rats, weighing 200-250 g, were
divided into seven groups; negative control (no intervention), sham 1(distilled
water), positive control (Pentylentetrazol [PTZ]), intervention group 1 (PTZ + Wi
Fi "off"), sham 2 (distilled water + Wi-Fi "off"), sham 3 (distilled water + Wi
Fi "on"), and intervention group 2 (PTZ + Wi-Fi "on"). The rats were exposed to
Wi-Fi for 2h at a distance of 30cm from a commercial Wi-Fi router. Convulsive
behaviors of rats were monitored and scored based on the intensity and type by
measuring latency/threshold time, number of convulsions, sum of scores and
durations of seizure, and duration of score 6 seizure. Kruskal-Wallis and Mann
Whitney U-tests were used to analyze the data. Results: Convulsion was observed
in interventions Group 4 and Group 7, and positive control. The mean number of
events, and sum of scores were significantly different in intervention 2 than
other two groups. However, the differences in mean threshold, mean sum of
durations and " time to show convulsion with score 6 " were not statistically
significant (P>0.05). Conclusion: Due to limitations of our study including the
sample size, these findings should be interpreted with caution. In this study,
exposure to 2.4 GHz Wi-Fi radiation showed significant beneficial effects on the
epileptic behaviour of rats. More experiments are needed to verify if these
exposures can be used as a therapeutic approach for amelioration of seizures in
epilepsy.
PMID- 29951446
TI - Correlation between Trunk-Pelvis Inter-Segmental Coordination Parameters during
Walking and Disability Level in Chronic Low Back Pain Patients.
AB - Background: Chronic low back pain (CLBP) disability has been particularly
frustrating because its treatment has been a great therapeutic challenge.
Disability has been suggested to depend on different factors that should be found
and considered in the medical management. The inter-segmental coordination is
often impaired in CLBP subjects; however, to the best of our knowledge, there is
no evidence about the relationship between the existence of coordination problems
and disability in CLBP patients. Objective: To evaluate the correlation between
sagittal plane trunk-pelvis inter-segmental coordination parameters during
walking and disability level in CLBP patients. Methods: Kinematic data were
collected from 16 non-specific CLBP (18-40 years) volunteers during walking.
Sagittal plane time-normalized segmental angles and velocities were used to
calculate continuous relative phase for each data point. Coordination parameters,
mean absolute relative phase (MARP) and deviation phase (DP) were derived to
quantify the trunk-pelvis coordination pattern and variability during gait
cycles, respectively. The disability level was quantified through Oswestry
Disability Index (ODI) questionnaire. Pearson correlation coefficient was used to
find the probable correlation between coordination parameters and disability
level. Results: The analysis demonstrated a significant correlation between
sagittal plane MARP or DP and disability level (%ODI) in CLBP subjects during
walking (r= -0.806 P<0.001 and r= -0.856, P<0.001, respectively). Conclusion:
This study demonstrated that the lower the MARP (more in-phase pattern) and DP
(less variable pattern) in the CLBP subjects, the more disability existing in
such patients. The results suggest that clinicians should look beyond pain
management when prescribing rehabilitation for CLBP and consider interventions
that target segmental coordination improvement to manage CLBP induced disability.
PMID- 29951447
TI - A Comparison of Six Ultrasound Stimulation Types on Pseudomonas Aeruginosa Growth
in Vitro.
AB - Background: This work evaluated the efficiency of common ultrasound stimulation
(U.S.S) types on bacterial growth in vitro using clinically relevant conditions.
Objective: To estimate different frequencies ultrasound bactericidal ability on
bacteria in bacteria of Pseudomonas Aeruginosa. Material and Methods: Six types
of U.S.S (continuous wave, 7w/cm2, 20 KHz; continuous wave, 35w/0.8L, 40 KHz;
continuous wave, 5w/cm2, 1.1 MHz; pulsed wave, 5w/cm2, 3.3 MHz; continuous wave,
5w/cm2, 3.3 MHz and continuous wave, 0.5w/cm2, 3.5 MHz) were applied to a
separate set of culture plates containing Pseudomonas aeruginosa for 10 minutes
at room temperature on four sample sets to inhibit bacterial growth. After US.S
treatment, the zone of inhibition at the US probe location was measured. Results:
Zone of inhibition measurements demonstrated a significant inhibitory effect for
continuous wave US.S of 5w/cm2, 1.1 MHz; pulsed wave US.S of 5w/cm2, 3.3 MHz; and
continuous wave US.S of 5w/cm2, 3.3 MHz (p < 0.05), but not for continuous wave
US.S of 7w/cm2, 20 KHz; continuous wave US.S of 35w/0.8L, 40 KHz; and continuous
wave US.S of 0.5w/cm2, 3.5 MHz. Conclusion: The data suggest that for infected
wounds, continuous wave US.S of 5w/cm2 and 1.1 MHz; pulsed wave US.S of 5w/cm2
and 3.3 MHz; and continuous wave US.S of 5w/cm2 and 3.3 MHz ultrasound treatments
may have an initial bacterial inhibitory effect, which does not significantly
change with subsequent treatments.
PMID- 29951448
TI - Closed- and Open-loop Deep Brain Stimulation: Methods, Challenges, Current and
Future Aspects.
AB - Deep brain stimulation (DBS) is known as the most effective technique in the
treatment of neurodegenerative diseases, especially Parkinson disease (PD) and
epilepsy. Relative healing and effective control of disease symptoms are the most
significant reasons for the tangible tendency in use and development of this
technology. Nevertheless, more cellular and molecular investigations are required
to reveal the detailed mechanism of DBS. Here, we reviewed the methods,
challenges and the ways to overcome the limitations of DBS. Also, challenges in
probe fabrication technology, material selection, related mechanical stability
and biocompatibility concerns are discussed. Finally, closed- and open-loop
stimulation systems were compared.
PMID- 29951449
TI - Design and Production of Two-piece Thyroid-neck Phantom by the Concurrent Use of
Epoxy Resin and Poly(methyl methacrylate) Soft Tissue Equivalent Materials.
AB - The aim of this report is to present a new two-piece thyroid-neck phantom
produced by the concurrent use of epoxy resin and poly(methyl methacrylate)
(PMMA: plexiglass) soft tissue equivalent materials. Accordingly, mass
attenuation coefficients of the epoxy resin and the plexiglass compounds were
obtained from simulation (NIST XCOM 3.1) and measurements (practical dosimetry)
and compared to those related to human soft tissue (ICRU 44). The thyroid-neck
phantom and thyroid gland dimensions were derived from scientific references and
the atlas of human anatomy, respectively. The thyroid phantom was designed by
CATIA V5R16 software and produced by the epoxy resin compound by three
dimensional printer. Other organs were designed by ProNest software and made by
the plexiglass sheets by CNC laser cutting machine. The mass attenuation
coefficients for the epoxy resin (50 keV- 20 MeV) and the plexiglass (0-20 MeV)
were comparable to human soft tissue (ICRU 44), all with standard relative
deviation beneath 5%. In addition, the SPECT images indicated the similarity
between human thyroid tissue and its phantom. In conclusion, this study proves
the feasibility and reliability of epoxy resin application in the production of
two-piece thyroid-neck phantom. This phantom can be applied in the calibration of
gamma camera systems, dosimetry and gamma spectrometry in the nuclear medicine
field.
PMID- 29951450
TI - Antibody targeting of phosphatidylserine for detection and immunotherapy of
cancer.
PMID- 29951451
TI - Mature teratoma of the bladder in adolescence: a case report and literature
review.
AB - Background: Teratomas are tumors consisting of two or three germ layers, seen
commonly during childhood. Teratomas have been reported to occur in various sites
and organs. Bladder teratoma is a very rare extragonadal tumor, moreover in
adults. Although teratomas are known as benign lesions in childhood, they may act
as malignant tumors when detected during adulthood. This requires total tumor
resection, particularly in adult cases, and the addition of radiotherapy and
chemotherapy in cases with the potential of malignancy. Case presentation: A very
rare case of teratoma of the bladder in a 17-year old Asian girl is presented.
The patient had chief complaints of hematuria. The diagnosis was made on
cystoscopy and confirmed histopathologically. Complete excision was possible. To
the authors' knowledge, this is the first such case reported from Indonesia and
the South East Asian region. Conclusion: A bladder teratoma mimics the
presentation of a bladder stone, clinically and radiologically. A dermoid cyst
should be considered as a differential diagnosis, especially when the stone
appears to be confined to the bladder wall during examination.
PMID- 29951452
TI - ARTHROSCOPIC PARTIAL MENISCECTOMY - SHORT-TERM CLINICAL OUTCOME IN AN ORTHOPAEDIC
CENTER IN SOUTHWESTERN NIGERIA.
AB - Background: Meniscal tears are one of the common causes of knee pain. Aim: To
evaluate the early clinical results of arthroscopic partial meniscectomy in the
treatment of meniscal tears. Study Design: This was a prospective study in which
consecutive patients presenting with meniscal injury, who met the inclusion
criteria were recruited for the study. Setting: National Orthopaedic Hospital,
Lagos. Methodology: Biodemographic data and clinical findings were obtained. The
visual analogue pain score and WOMET score were computed pre-operatively and at
least 6-months post-operatively and these values compared using the Wilcoxon's
signed rank. The level of significance was set at 0.05. Results: A total of 19
patients with 19 knees were included. Degenerative longitudinal tears were the
commonest findings in 15 (79%), complex tears in 3 (16%) and radial tear in 1
(5%). The medial meniscus was more affected (52%) than lateral meniscus (48%).
The red-white zone was involved in 12 (63%) cases and the white-white zone in 5
(37%). The median duration of follow up was 7 months while the median (IQR) WOMET
score decreased from 59 (IQR =22) to 26.5(IQR=23), (Z= -3.409, P=001 ) and the
visual analogue pain rating scale improved from 5 (IQR=1.5) to 3 (IQR=2.5) (Z=
3.346, P=001 ). Conclusion: Arthroscopic partial meniscectomy offers a good short
term clinical outcome for patients with knee pain secondary to meniscal injury.
PMID- 29951453
TI - THE DISTRIBUTION, HISTOLOGIC PROFILE AND CLINICAL PRESENTATION OF
GASTROINTESTINAL MALIGNANCIES IN LAGOS, NIGERIA.
AB - Background: Gastrointestinal malignancies have continued to record higher
incidence and therefore pose significant public health burden in terms of
morbidity and mortality. Aim: To evaluate the sociodemographic, histologic and
clinical distribution of patients with gastrointestinal malignancies diagnosed
between July 2009 and March 2016. Setting: Lagos University Teaching Hospital,
Idi-Araba, south-west Nigeria. Methodology: Using a retrospective study design,
all the patients with histologic diagnosis of gastrointestinal malignancies were
recruited and their bio-data, clinical, histologic and treatment data were
extracted from their hospital records. Results: Of the 106 cases of
gastrointestinal malignancies in this study, the age range was 30-82 years with a
mean of 55.9+/-13 years and a peak age bracket of 50-59 years; the male/female
ratio was 1.2:1. The most common sites were colorectum (79.3%), stomach (7.6%),
anus (6.6%), liver (4.7%), and pancreas (0.9%). Adenocarcinoma was the most
common histologic subtype (89.62%), followed by squamous cell carcinoma (2.83%)
and gastrointestinal stromal tumors (1.89%). The most common complaints were
abdominal pain (54.7%), constipation (38.7%), palpable abdominal swelling/masses
(35.9%), bleeding (33.0%), and weight loss (17.0%). The tumors were treated with
chemotherapy, surgery, and radiotherapy, either singly or in combination, in
97.2%, 83.0%, and 30.2% respectively. Conclusion: In this study, colorectal
cancers are still the most prevalent type of gastrointestinal malignancies with a
male preponderance, and individuals between 40-59 years are at greater risk. The
significant involvement of individuals who constitute the bulk of the workforce
and are the most productive labor in the country points at the need to develop
strategies aimed at reducing the incidence of gastrointestinal malignancies.
PMID- 29951454
TI - AN AUDIT OF ORAL AND MAXILLOFACIAL PROCEDURES UNDER GENERAL ANAESTHESIA AT THE
UNIVERSITY COLLEGE HOSPITAL IBADAN, NIGERIA.
AB - Background: Operating theatre time management is a constant source of tension
among the healthcare professionals responsible for the use of the facility. It is
important that all effort should be geared at optimal utilization of available
resources and minimization of waste. Aim: To appraise time management, frequency
and duration of surgical procedures, frequency and determinants of blood
transfusion in oral and maxillofacial surgery. Design of the study: Prospective
clinical study. Setting: The University College Hospital, Ibadan. Nigeria.
Methodology: This was a cross-sectional study of consecutive patients who had
maxillofacial surgical procedures. Information was collected on number of cases
scheduled per list, number of cases done per list, each patient's biodata, time
intervals between patient arrival and departure from operating theatre, route and
duration of intubation, type of surgical procedure, surgical time, preoperative
and postoperative packed cell volume estimations, volume of blood loss and the
frequency and volume of blood transfusions. Results: The main points of delay
were identified as the patient wait at the theatre reception and in the operating
suite before intubation. Mandibulectomy procedures were the longest procedures
with approximately five (5) hours, followed by maxillectomy with four (4) hours
and maxillofacial trauma with three and a half (3.5) hours. Maxillectomy
procedures had highest transfusion probability. The surgical time and the
estimated blood loss significantly determined whether a patient would be
transfused or not. The nasotracheal was the commonest route of intubation while
cleft surgeries were the most frequent procedures performed followed by trauma
surgeries. Majority of the patients were not transfused and two units of blood
was the most frequent transfused volume for a patient. Conclusion: The main areas
of delay have been identified as patients' waiting periods before the surgical
procedures. The reasons why these delays occur need to be investigated and
addressed to have an optimally functional facility. Reservation of blood for
maxillofacial surgical procedures should be based on the anticipated need for
blood transfusion for the particular procedure.
PMID- 29951455
TI - Efficacy of topical sucralfate vERSUs silver sulfadiazine in the management of
burns: A 1-year randomized controlled trial.
AB - Background: Several medications and topical agents have been used for burn
injuries. Among them, 1% silver sulfadiazine is the most commonly used topical
agent for partial thickness burns. Recent studies have reported that the healing
of burns is delayed by silver sulfadiazine. Search for the ideal topical agent
for burn injuries is an ongoing research. The current study is undertaken with
sucralfate as topical agent for dressing of burn injuries. Aim: To compare the
efficacy of topical sucralfate with silver sulfadiazine in the healing of second
degree superficial burns. Study design: A one-year randomized controlled trial.
Setting: Department of General Surgery, JN Medical College and KLES Dr. Prabhakar
Kore Hospital and Medical Research Centre, Belagavi, India. Methodology: A total
of 60 patients with < 50% second degree superficial burns were enrolled for the
study. Patients were equally divided into two groups. Patients in group A were
treated with topical sucralfate dressing and those in group B were treated with
dressing. Demographics, history, physical, and systemic examinations of the
patients were recorded. Routine blood investigations and culture and sensitivity
were also performed. SPSS 20.0 was used for the analysis. Results: In group A,
the granulation appeared in less than 7 days in 15 (50%) patients, where as in
group B, granulation appeared between 15 and 20 days in 17 (56.67%) patients (p =
0.149). The mean day of granulation was 8.11+/-3.92 days in group A compared to
8.93+/-3.29 days in group B (p = 0.396). The wound culture on day 1, 7 and 14
(p>0.050) did not differ significantly in both the groups. Conclusion: Overall,
topical sucralfate dressing is efficacious in terms of development of early
granulation in the healing of second-degree superficial burns compared to silver
sulfadiazine dressing while antimicrobial effect is comparable to that of silver
sulfadiazine dressing. It hastened burn wound healing process in second-degree
superficial burns and should be used as an alternative agent or in combination
with other topical agents. However, multicentric trials with bigger sample size
are needed to strengthen the concept.
PMID- 29951456
TI - PATTERN OF AGENESIS AND MORPHOLOGIC VARIATION OF THE MAXILLARY LATERAL INCISORS
IN NIGERIAN ORTHODONTIC PATIENTS.
AB - Background: Congenitally missing or aberrant morphology of maxillary lateral
incisors may cause aesthetic and functional impairment of the affected
individual. There is however paucity of information on its prevalence and pattern
of presentation among Nigerians. Aim: To determine the prevalence of agenesis,
peg and small maxillary lateral incisors in Nigerian orthodontic patients in
Lagos, Nigeria. Study Design: A retrospective study. Setting: Orthodontic Unit,
Lagos State University Teaching Hospital, Lagos, Nigeria. Methodology: The
hospital folders, dental casts and panoramic radiographs of 611 patients between
December 2013 and September 2014 were reviewed. The data obtained included
congenital absence, size and shape of maxillary lateral incisors. Results: Out of
the 611 patients studied, agenesis of maxillary lateral incisors was found in
14(2.3%) of the patients with 12(2.0%) females being significantly higher than
2(0.3%) males. The prevalence of maxillary peg laterals was 4.6% with no gender
difference, while the prevalence of maxillary small lateral incisors was 3.9%
also with no gender difference. A total of 20 maxillary lateral incisors were
congenitally missing, while 35 peg laterals were recorded and 30 small lateral
incisors were found. Unilateral agenesis of maxillary lateral incisor was more
prevalent in 8(57%) patients than bilateral agenesis found in 6(43%) with
significant preference for the right side 7(50%) than 1(7%) on the left.
Unilateral peg maxillary lateral incisor was more prevalent in 21(75%) than
bilateral peg 7(25%) with significant preference for the left side 16(57.1%).
Unilateral small maxillary lateral incisor 18(75%) was more prevalent than
bilateral small lateral incisor 6(25%) with preference for the left side
10(41.7%). Conclusion: We found that the prevalence rates for lateral incisor
agenesis, peg and small lateral incisor among Nigerian orthodontic patients were
2.3%, 4.6% and 3.9% respectively.
PMID- 29951457
TI - LONG TERM OUTCOMES OF AUGMENTED TRABECULECTOMY WITH 5-FLUOROURACIL IN NIGERIA.
AB - Background: Glaucoma in sub-Saharan Africa has been described as a surgical
disease because of the high cost of medical treatment, poor compliance and
unavailability of medications. Aim: This study reports the long-term outcomes and
complication rates following trabeculectomy with 5-fluorouracil in a case series
of Nigerians. Design of study: This was a retrospective, observational, non
comparative case series. Setting: University College Hospital, Ibadan, Nigeria.
Methodology: Each patient had complete ophthalmic evaluation. The post-operative
intraocular pressure (IOP), visual acuity outcomes and post operative
complications were assessed. The World Glaucoma Association consensus on surgical
outcome was used to evaluate surgical outcome. Results: Of the 292 patients who
presented with glaucoma during this period, a total of 47 eyes of 31 patients
(10.6%) had trabeculectomy with 5-FU. The mean presenting intraocular pressure
(IOP) was 31.8+/-12.2mmHg. At three years post-operatively, 48.5% achieved
complete success without medications while 90.9% achieved success with or without
medications at an IOP cut off of <=21mmHg. At the same time point of 3 years and
an IOP cut off of <=15mmHg, 63.6% achieved success with or without medications.
At a mean post-operative period of 43+/- 19.6 months, (range 12-86 months), mean
IOP had reduced from a preoperative mean of 31.8+/-12.2mmHg to 15.4+/-4.7mmHg
(P<0.001). Conclusion: Trabeculectomy with 5-Fluorouracil is effective in the
long term in reducing IOP with minimal complications in this population of
Nigerians.
PMID- 29951458
TI - The Correlation Between Body Mass Index On The Length From Skin To Lumbar
Epidural Space In Nigerian Adults.
AB - Background: One of the factors that determine success of an epidural anaesthetic
is correctly locating the epidural space. Being able to predict the skin to
lumbar epidural space distance can serve as a guide to performing epidural
anaesthesia and in turn increase the success rate. Aim: To determine the
correlation between the BMI, gender and age on SLESD of adults scheduled for
elective surgical procedure under lumbar epidural anaesthesia. Design of Study:
It was across sectional descriptive study carried out on consenting patients
scheduled for elective surgery under lumbar epidural anaesthesia. Setting: The
study was carried out in the main theatre complex and the obstetric theatre of
the University of Ilorin Teaching Hospital, Ilorin, Nigeria. Methodology: One
hundred and twenty patients of ASAI and II physical status between the ages of18
65years scheduled for elective surgical procedures under epidural anaesthesia
were enrolled into the study. This was a cross sectional descriptive study
involving both sexes. Using a septic technique epidural anaesthesia was
established in the sitting position using the midline approach at L3/L4orL4/L5
interspace. The epidural space was identified by loss of resistance to air.
TheSLESD in centimetres (cm) was rounded up to the nearest 0.25cm. Data were
collected and analyzed using Spearman's correlation to evaluate the relationship
between BMI, weight, sex, age, height and the SLESD. Results: The mean SLESD was
4.60+/-0.83 cm with a range of 3cm-8cm. The SLESD was significantly influenced by
BMI and weight with both having positive correlation and P value of 0.001 and
0.004 respectively. We formulated a relationship between skin to lumbar epidural
space and body mass index based on linear regression analysis: Depth cm= a + b *
(BMI)Where a =3.33 and b =0.05.There was no correlation between SLESD and height,
age or sex of the patients. Conclusion: There was positive linear correlation
between the body mass index, body weight and the skin to lumbar epidural space
distance. Whereas, the age, sex and height had no correlation with the skin to
lumbar epidural space distance.
PMID- 29951459
TI - MORNING GLORY SYNDROME IN A NIGERIAN - A CASE REPORT.
AB - Morning glory syndrome is an uncommon congenital excavated optic disc anomaly
that can impair vision and may be associated with ocular and non-ocular
abnormalities. It has a characteristic fundoscopic appearance which consists of a
large excavated disc with radial vessels and a central turf of glial tissue
situated within a funnel shaped excavation of the posterior fundus. It is more
common in Caucasians than in blacks. We report a case of this uncommon congenital
anomaly of the optic disc in a Nigerian male.
PMID- 29951460
TI - Peer-Reviewed Abstracts of Scientific Paper Presentation at The 57th Annual
Conference Of The West African College Of Surgeons at Ougadougou, Burkina Faso
26th February - 4th March 2017.
PMID- 29951461
TI - ARTHROSCOPIC MENISECTOMY.
PMID- 29951462
TI - MARGINAL MICROLEAKAGE PROPERTIES OF ACTIVA BIOACTIVE RESTORATIVE AND NANOHYBRID
COMPOSITE RESIN USING TWO DIFFERENT ADHESIVES IN NON CARIOUS CERVICAL LESIONS -
AN IN VITRO STUDY.
AB - Background: In clinical practice, the restoration of non-carious cervical lesions
is a challenge, because most of the time the cervical margin is located in
cementum or dentin. This characteristic makes the cervical margin more
susceptible to microleakage, causing cavosurface stains, postoperative
sensitivity and also favours the incidence of carious lesions. Aim: To compare
and evaluate the microleakage in class V lesions restored with Activa Bioactive
restorative and nanohybrid composite resin using two different bonding agents.
Methodology: In this study, 50 class V cavities were prepared in freshly
extracted teeth. The samples were randomly divided into 5 groups (n=10),
depending on the type of restorative material and bonding agent: Group 1 - Activa
Bioactive (Pulpdent, USA) + No bonding, Group 2 - Activa Bioactive + Tetric N
Bond (Ivoclar Vivadent, Colombia),Group 3 - Activa Bioactive + G Bond (GC Corp.,
Tokyo, Japan), Group 4 - Nanohybrid Composite (Ivoclar Vivadent, Colombia) +
Tetric N Bond, Group 5 - Nanohybrid Composite + G Bond. The samples were restored
with their respective material based on the group. After curing all the specimens
were subjected to thermocycling and cyclic loading. Specimens were stained with
2% rhodamin b dye and evaluated for dye penetration. Results: Results were
obtained based on Kruskal Wallis and Mann Whitney U- test. Conclusion: Within the
limitations of this study, none of the materials were free from microleakage. All
the materials showed more microleakage at gingival margins compared to occlusal
margins. Among all the groups Activa Bioactive restorative when used in
combination with Tetric N Bond showed the least microleakage.
PMID- 29951463
TI - Hearing dynamics in patients with traumatic tympanic membrane perforation.
AB - Background: Hearing distortions from trauma to the ear could occur by direct
perforation of the tympanic membrane. Aim: To characterize hearing thresholds in
patients with traumatic tympanic membrane perforation and changes in hearing
occurring in the course of treatment. Study design: Prospective analytical study.
Setting: Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria.
Methodology: We prospectively entered in a proforma the demographics of 60
patients with traumatic tympanic membrane perforation at the teaching hospital in
Sagamu, Nigeria over a period of five years as well as their hearing assessment
with pure tone audiometry at initial contact and six weeks post-injury. The type
of hearing loss, pure tone average and air-bone gaps were recorded. Hearing
changes between initial and second audiometric assessments were analyzed and
compared. Results: The data obtained from 60 patients with 73 traumatized ears
were analyzed. In all, 64 (87.7%) of the ears had hearing loss while 33(45.2%)
had conductive hearing loss. Injured ears had significantly worse hearing and
higher air-bone gaps ABGs compared with non-traumatized ears. There was notable
improvement in hearing thresholds and closure of air-bone gaps in the course of
treatment, which was significantly more at the low frequencies compared with the
high frequencies. Conclusion: Patients with traumatic tympanic membrane
perforation majorly had conductive hearing loss in the injured ears with
audiometric confirmed air-bone gaps and increased hearing thresholds which were
not frequency dependent. There was appreciable improvement in hearing parameters
over time, significantly more at the low frequencies.
PMID- 29951464
TI - SURGICAL AND ORTHODONTIC TREATMENT METHODS IN PATIENTS WITH BIMAXILLARY
PROTRUSION - A SYSTEMATIC REVIEW.
AB - Background: The acceptable goal of treatment of bimaxillary protrusion is the
retraction of maxillary and mandibular incisors with a resultant decrease in soft
tissue convexity. This can be achieved by both surgical and orthodontic treatment
methods. The aim of this study was to conduct a systematic literature review on
the outcome of either method and other associated factors. Methodology:
Electronic databases (PubMed, Cochrane, Medline) were searched to identify
studies that assessed hard and soft tissues changes in patients treated for
bimaxillary protrusion with surgery or orthodontics. Abstracts that appeared to
fulfill the initial selection criteria were selected, and the full-text original
articles were retrieved and analyzed. Only articles that fulfilled the final
selection criteria were finally considered. Their references were also hand
searched for possible missing articles from the database searches. Results: The
initial literature search identified 215 articles while 71 full text articles
were retrieved for further analysis. Twenty-four publications were included in
the final review. Most of the studies were retrospective with no randomized
control trial. The studies showed high heterogeneity in type and technique of
space closure, anchorage, orthodontic appliance and surgery. Surgical treatment
was carried out for more severe cases than orthodontic treatment. Both methods
achieved increased inter-incisal angle, however shorter treatment time appeared
to be associated with surgery. Conclusion: Satisfactory outcome were achieved
with both treatment protocols. However, surgery was more indicated in severe
cases.
PMID- 29951465
TI - REASONS FOR LOSS OF THE PERMANENT TEETH IN PATIENTS IN KANO, NORTH WESTERN
NIGERIA.
AB - Background: Loss of permanent dentition is often of great concern to patients,
apart from the aesthetic consequences in the anterior region of the mouth, such
loss has no natural form of replacement. Aim: To determine the pattern of tooth
loss among patients attending the Dental Clinic at a Nigerian teaching hospital.
Material and Methods: The case files of patients who attended the Dental Clinic
of Aminu Kano Teaching Hospital, Kano between January and December 2012 with one
or more missing tooth were retrospectively analyzed. The information collected
included age, gender, educational level, residential area, missing tooth/teeth
and reasons for the loss. The data were analyzed using SPSS version 13.0
(Chicago, Illinois). A p-value of less than 0.05 was considered significant.
Results: A total of 1100 missing teeth were recorded involving 960 patients
within the period of one year. Males comprises 520(54.2%) and females 440(45.8%).
The most predominant age group was the 21-30 years with a mean of 29.53 +12.41
years and this comprised 48.2% of the cases. Caries related extractions (65.6%)
were the most common cause of tooth loss followed by periodontal disease in 13.1%
of cases and symptomatic impacted tooth in 9.8%. Gender affects the etiology of
tooth loss was significant with males having more tooth loss (X2=52.93, df=6,
P=0.001). There was a significant association between age and the pattern of
tooth loss with tooth loss due to periodontal diseases occurring in the older age
groups (X2=1071.67, p=0.001). Conclusion: Dental caries and periodontal diseases
still remain the main causative factors for tooth loss in this environment, more
common in men and rural dwellers.
PMID- 29951466
TI - EXPERIENCE WITH Ponseti Protocol and Achilles Tenotomy in THE MANAGEMENT OF
Clubfoot at the Lagos STATE UNIVERSITY TEACHING HOSPITAL, lagos, Nigeria.
AB - Background: Achilles tenotomy is very frequently performed to correct persistent
equinus deformity in Ponseti clubfoot management worldwide. Aim: To review the
frequency of Achilles tenotomy and outcome of treatment of idiopathic clubfoot
using the Ponseti method. Setting: Lagos State University Teaching Hospital,
Lagos, Nigeria. Design of the study: Prospective observational study.
Methodology: All the patients with idiopathic clubfoot treated using the Ponseti
protocol in the clubfoot clinic between June 2013 and October 2015 were
recruited. The data obtained included biographic data, Pirani score at
presentation, number of casts until initial correction, number of feet that had
Achilles tenotomy and complications. They were recorded in the International
Clubfoot Registry (ICR) hosted by the Centre for Bioinformatics and Computational
Biology at the University of Iowa, USA and were analysed using the ICR software.
Results: Of the 124 patients in this study, 77 (62.1%) had bilateral foot
deformities (154 feet) and 47 patients (37.9%) had unilateral clubfoot making a
total of 201 clubfeet. Their ages at presentation ranged from 1 week to 6 years.
Forty (32.3%) patients were aged less than 1 month, 58(46.8%) aged between 1 and
6 months, 12 (9.7%) aged between 6 and 12 months and while 14 (11.3%) aged 12
months and above. There were 77 males and 47 females with a male/female ratio of
1.6:1. The initial Pirani score was 4 and above in 140 feet with a mean of 4.3.
Correction was achieved after a mean of 5.2 casts and tenotomy was performed in
45 (23.1%) feet before foot abduction brace application. Conclusion: This study
has shown that congenital idiopathic clubfeet can be managed with good outcome
using the Ponseti protocol with a reduced frequency of Achilles tenotomy.
PMID- 29951467
TI - MODIC CHANGES IN ADULTS WITH CHRONIC LOW BACK PAIN IN NORTH CENTRAL NIGERIA.
AB - Background: Modic changes in the endplates of the vertebral bodies have been
associated with low back pain. There is however paucity of information on the
pattern of Modic changes in the lumbosacral spine in Nigerians with low back
pain. Aim: To determine the prevalence of Modic changes in patients with chronic
low back pain in our environment. Design of study: Cross-sectional longitudinal
study. Settings: University of Ilorin Teaching Hospital, Ilorin, Nigeria.
Methodology: A total of 147 consecutive adults who had MRI of the lumbosacral
spine for chronic low back pain were examined for the presence of Modic changes.
Results: 35(23.8%) individuals had Modic changes present out of I47 patients with
low back pain evaluated.Out of the 735 lumbar vertebral endplates evaluated,
90(12.2%) had Modic changes present. Among the endplates with Modic changes,
36(40%) were type I, been the most common in our sample, while 27(30%) were type
II and type III each. Conclusion: This study has shown that Modic changes
occurred more frequently at the end plates of lower lumbar vertebrae(L4/L5, and
L5/S1) and Type I was the most common while Type II and III had equal prevalence;
the changes occurred more frequently with increasing age suggesting these changes
are degenerative in nature.
PMID- 29951468
TI - A CEPHALOMETRIC ANALYSIS OF THE MORPHOLOGY AND SIZE OF SELLA TURCICA IN NIGERIANS
WITH NORMAL AND BIMAXILLARY INCISOR PROTRUSION.
AB - Background: It has been suggested that bimaxillary protruded anterior teeth may
be related to the sella turcica anatomically and embryologically through their
common progenitors. Aim: This study assessed the morphological variations and
linear dimensions of sella turcica in a Nigerian population with normal and
bimaxillary protruded teeth. Methodology: Lateral cephalometric radiographs of
orthodontic patients were assessed. Sixty-five randomly selected radiographs of
patients with bimaxillary proclination were compared with 52 radiographs of
normal incisor relationship subjects. Cephalometric landmarks and dimensions of
sella turcica were identified and traced manually and measured. Data were
analyzed using Statistical Package for Social Sciences, (SPSS version 16.0 for
windows, SPSS Inc, Chicago). Descriptive and inferential statistics were used and
significance level was set at P<0.05. Results: Sella turcica with normal
morphology accounted for 61.5% in the population while the least was sella
turcica bridge with only 6%. The sella turcica dimensions were consistently
larger in young adults than the adolescents, however, no statistically
significant difference was reported in its length and diameter (p>0.05) except
for the depth (p<0.05). Similarly, there were no statistically significant
differences in sella turcica dimensions in relation to gender and incisor
relationship. Conclusion: The prevalence of normal morphology of sella turcica in
the population was 61.5%. There was no statistically significant difference in
sella turcica dimensions between normal and bimaxillary protrusion subjects
(p>0.05). Similarly, no significant differences in dimensions were observed in
gender and age groups (p>0.05) except for the depth of sella turcica that was
significantly larger in young adults (p<0.05).
PMID- 29951470
TI - Peer-Reviewed Abstracts of Scientific Paper Presentation at The 57th Annual
Conference Of The West African College Of Surgeons at Ougadougou, Burkina Faso
26th February - 4th March 2017.
PMID- 29951469
TI - Clinical Presentation and Outcome of Impalement Craniocerebral Injuries - A CASE
SERIES.
AB - Non-missile, low-velocity penetrating craniocerebral injuries are uncommon among
civilians and unlike missile injuries, are associated with localized brain injury
and subsequent good outcome if managed appropriately. Penetrating injuries to the
brain caused by a retained, relatively blunt or sharp object that perforate the
brain along its longitudinal axis producing a wound track corresponding to its
length of penetration, are called impalement injuries. Most of the impalement
craniocerebral injuries are accidental and varying objects have been reported. We
report our experience with the management of seven cases of impalement
craniocerebral injuries. Five of the patients were adult male while two female
children were involved. One case was from assault, others resulted from
accidental injury. Left side of the cranium was more commonly involved. The
impaled objects in this study included a lead pencil, a screw driver, a branch of
a tree, and other metallic objects. Most of the patients had craniectomy and
water tight dura repair during remover of the impaled object. All patients made
good recovery following surgical intervention. Management principles entail early
recognition, deliberate and careful debridement, and judicious antibiotic
therapy. The surgical approach to these injuries varies, depending on the route
of entry.
PMID- 29951471
TI - Impalement head injuries.
PMID- 29951472
TI - Comment on "Establishing a Porcine Model of Small for Size Syndrome following
Liver Resection".
PMID- 29951473
TI - A Pathogenic Relationship of Bronchopulmonary Dysplasia and Retinopathy of
Prematurity? A Review of Angiogenic Mediators in Both Diseases.
AB - Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are common
and significant morbidities of prematurely born infants. These diseases have in
common altered and pathologic vascular formation in the face of incomplete organ
development. Therefore, it is reasonable to question whether factors affecting
angiogenesis could have a joint pathogenic role for both diseases. Inhibition or
induced expression of a single angiogenic factor is unlikely to be 100% causative
or protective of either of BPD or ROP. It is more likely that interactions of
multiple factors leading to disordered angiogenesis are present, increasing the
likelihood of common pathways in both diseases. This review explores this
possibility by assessing the evidence showing involvement of specific angiogenic
factors in the vascular development and maldevelopment in each disease.
Theoretical interactions of specific factors mutually contributing to BPD and ROP
are proposed and, where possible, a timeline of the proposed relationships
between BPD and ROP is developed. It is hoped that future research will be
inspired by the theories put forth in this review to enhance the understanding of
the pathogenesis in both diseases.
PMID- 29951474
TI - Does Masked Hypertension Cause Early Left Ventricular Impairment in Youth?
AB - Objectives: Masked hypertension (MH) is not uncommon in the youth and may
increase risks of long-term cardiovascular impairment. However, little is known
about the subclinical heart damage in this group of patients. Currently, 3-layer
speckle tracking imaging based on two-dimensional echocardiography is feasible to
detect the early signs of myocardial damage. We therefore aimed to investigate
whether subtle changes of cardiac function occurred in the young MH patients by
using advanced quantification with layer-specific speckle tracking. Methods: A
total of 40 adolescents with MH (age 18 +/- 3 years, 73% males) and 40 age-,
gender-, race-, and height-matched normotensive volunteers were enrolled in our
study. MH was defined as one or more of the ambulatory blood pressure (BP)
parameters (24-h, daytime and night-time average BPs) higher than >= 95th
percentile for gender and height according to the local reference. Both
comprehensive two-dimensional echocardiography with layer-specific strain
analysis and 24-h ambulatory BP monitoring were performed. Longitudinal strain
and circumferential strain in endocardial, mid-myocardial, and epicardial layers
were determined accordingly with the dedicated software (EchoPAC software version
201, GE Healthcare, Horten, Norway). Results: Compared with normotensive
controls, youths with MH had higher ambulatory pulse rate and left ventricular
mass index, and were more obese. Interestingly, similar ventricular volumes and
ejection fraction were observed in the study groups, but further analysis with
layer-specific strains revealed that endocardial and mid-myocardial longitudinal
and circumferential mechanical function were decreased in the young MH subjects
when compared to normotensive individuals (all p < 0.05). However, there were no
difference regarding radial strain and apical rotation derived from traditional
speckle tracking analysis. Conclusion: Subclinical change of LV mechanic function
assessed by layer-specific speckle tracking is present in youth with MH despite
considered as normal with conventional ways.Thus, MH in youth should be monitored
closely instead of labeling as an entirely benign entity.
PMID- 29951476
TI - Building a Multi-Institutional and Interdisciplinary Team to Develop a Zoonotic
Tuberculosis Roadmap.
AB - Tuberculosis (TB), as the major infectious disease in the world, has devastating
consequences for not only humans, but also cattle and several wildlife species.
This disease presents additional challenges to human and veterinary health
authorities given the zoonotic nature of the pathogens responsible for the
disease across species. One of the main public health challenges regarding
zoonotic TB (ZTB) caused by Mycobacterium bovis is that the true incidence of
this type of TB in humans is not known and is likely to be underestimated. To
effectively address challenges posed by ZTB, an integrated One Health approach is
needed. In this manuscript, we describe the rationale, major steps, timeline,
stakeholders, and important events that led to the assembling of a true
integrated multi-institutional and interdisciplinary team that accomplished the
ambitious goal of developing a ZTB roadmap, published in October, 2017. It
outlines key activities to address the global challenges regarding the
prevention, surveillance, diagnosis, and treatment of ZTB. We discuss and
emphasize the importance of integrated approaches to be able to accomplish the
short (year 2020) and medium term (year 2025) goals outlined in the ZTB roadmap.
PMID- 29951475
TI - Pulmonary Valve Regurgitation: Neither Interventional Nor Surgery Fits All.
AB - Introduction: PV implantation is indicated for severe PV regurgitation after
surgery for congenital heart defects, but debates accompany the following issues:
timing of PV implantation; choice of the approach, percutaneous interventional
vs. surgical PV implantation, and choice of the most suitable valve. Timing of
pulmonary valve implantation: The presence of symptoms is class I evidence
indication for PV implantation. In asymptomatic patients indication is agreed for
any of the following criteria: PV regurgitation > 20%, indexed end-diastolic
right ventricular volume > 120-150 ml/m2 BSA, and indexed end-systolic right
ventricular volume > 80-90 ml/m2 BSA. Choice of the approach: percutaneous
interventional vs. surgical: The choice of the approach depends upon the
morphology and the size of the right ventricular outflow tract, the morphology
and the size of the pulmonary arteries, the presence of residual intra-cardiac
defects and the presence of extremely dilated right ventricle. Choice of the most
suitable valve for surgical implantation: Biological valves are first choice in
most of the reported studies. A relatively large size of the biological
prosthesis presents the advantage of avoiding a right ventricular outflow tract
obstruction, and also of allowing for future percutaneous valve-in-valve
implantation. Alternatively, biological valved conduits can be implanted between
the right ventricle and pulmonary artery, particularly when a reconstruction of
the main pulmonary artery and/or its branches is required. Hybrid options:
combination of interventional and surgical: Many progresses extended the
implantation of a PV with combined hybrid interventional and surgical approaches.
Major efforts have been made to overcome the current limits of percutaneous PV
implantation, namely the excessive size of a dilated right ventricular outflow
tract and the absence of a cylindrical geometry of the right ventricular outflow
tract as a suitable landing for a percutaneous PV implantation. Conclusion:
Despite tremendous progress obtained with modern technologies, and the endless
fantasy of researchers trying to explore new forms of treatment, it is too early
to say that either the interventional or the surgical approach to implant a PV
can fit all patients with good long-term results.
PMID- 29951477
TI - Challenges Facing Asian Sex Workers in Western Australia: Implications for Health
Promotion and Support Services.
AB - Introduction: Asian sex workers are a significant part of the Australian sex
industry. Criminal laws, racism, isolation, poor English language skills and
stigma and discrimination combine to increase the vulnerability of Asian sex
workers in Australia. To inform service delivery and potential legislative
reform, we undertook a study of sex worker health and safety in Western Australia
with a focus on Asian sex workers. Methods: This was a mixed methods study in
which peer researchers played an essential role. We undertook a survey (available
online and in paper form and translated into three languages other than English),
semi-structured interviews with sex workers, and interviews with key advisors.
Results: In our study, Asian sex workers were older, had lower levels of
education, more likely to have sex work as their main source of income, work
longer hours and work exclusively in a shop-front massage parlor compared to
their non-Asian counterparts. The vast majority of Asian sex workers in our study
said they had poor English language skills and the greatest proportion spoke
Chinese languages. Sex work had a positive impact on the well-being of many
respondents, and their level of psychological distress was similar to the general
Australian population. Stress and "bad clients" were common negative impacts of
sex work. Asian study participants were less likely than their non-Asian
counterparts to smoke, undertake risky drinking or use illicit drugs. A similar
proportion of Asian sex workers reported being assaulted compared to their non
Asian counterparts. Discussion/Conclusion: The major challenges facing Asian sex
workers in WA seem to be stigma and discrimination, stress, social isolation, and
confusion about their legal standing leading to a fear of authorities,
particularly the police. Our findings support the need for enhanced targeted peer
based health promotion outreach services for Asian sex workers, increased Asian
language services in sexual health clinics and decriminalization of sex work.
PMID- 29951478
TI - A Multi-Step Chromatographic Approach to Purify Radically Generated Ferulate
Oligomers Reveals Naturally Occurring 5-5/8-8(Cyclic)-, 8-8(Noncyclic)/8-O-4-,
and 5-5/8-8(Noncyclic)-Coupled Dehydrotriferulic Acids.
AB - Ferulate-mediated cross-linking of plant cell wall polymers has various
implications on the quality of plant based food products, forage digestibility,
and biomass utilization. Besides dehydrodiferulic acids (DFA), dehydrotriferulic
acids (TriFA) gained increasing interest over the past two decades, because they
potentially cross-link up to three polymers. Here, we describe a separation
strategy to obtain several TriFA as analytical standard compounds from a reaction
mixture after radical coupling of ethyl ferulate. By using silica flash
chromatography, Sephadex LH-20 chromatography, and reversed phase HPLC, six known
TriFA as well as three previously unidentified ferulic acid trimers were
obtained, and their structures were characterized by mass spectrometry and NMR
spectroscopy (1H, HSQC, COSY, HMBC, and NOESY). The novel trimers were identified
as 5-5/8-8(cyclic)-, 8-8(noncyclic)/8-O-4-, and, tentatively, 5-5/8-8(noncyclic)
TriFA. Natural occurrence of these TriFA in plant cell walls was demonstrated by
LC-MS/MS analyses of alkaline cell wall hydrolyzates.
PMID- 29951479
TI - Isolation and Synthesis of Misszrtine A: A Novel Indole Alkaloid From Marine
Sponge-Associated Aspergillus sp. SCSIO XWS03F03.
AB - A novel indole alkaloid, misszrtine A (1), was isolated from marine sponge
derived fungus Aspergillus sp. SCSIO XWS03F03. The planar structure of 1 was
assigned by analysis of spectroscopic data, the absolute configuration of which
was unambiguously determined by total synthesis. Compound 1 represents the first
example of N-isopentenyl tryptophan methyl ester with a phenylpropanoic amide
arm, which exhibited a potent antagonistic activity on HL60 (IC50 = 3.1 MUM) and
LNCaP (IC50 = 4.9 MUM) cell lines. Bioactivity evaluation reveals that functional
group on indole nitrogen of 1 has a great effect on its cytotoxity, which
provides a mean to probe the structure-activity relationships of 1.
PMID- 29951480
TI - Synthesis and Electrochemical Performance of Molybdenum Disulfide-Reduced
Graphene Oxide-Polyaniline Ternary Composites for Supercapacitors.
AB - Molybdenum disulfide/reduced graphene oxide/polyaniline ternary composites
(MoS2/rGO/PANI) were designed and synthesized by a facile two-step approach
including hydrothermal and in situ polymerization process. The MoS2/rGO/PANI
composites presented an interconnected 3D network architecture, in which PANI
uniformly coated the outer surface of the MoS2/rGO binary composite. The
MoS2/rGO/PANI composites with a weight percent of 80% (MGP-80) exhibits the best
specific capacitance (570 F g-1 at 1 A g-1) and cycling stabilities (78.6%
retained capacitance after 500 cycles at 1 A g-1). The excellent electrochemical
capacitive performance is attributed to its 3D network structure and the
synergistic effects among the three components that make the composites obtain
both pseudocapacitance and double-layer capacitance.
PMID- 29951483
TI - Benchmarking cryo-EM Single Particle Analysis Workflow.
AB - Cryo electron microscopy facilities running multiple instruments and serving
users with varying skill levels need a robust and reliable method for
benchmarking both the hardware and software components of their single particle
analysis workflow. The workflow is complex, with many bottlenecks existing at the
specimen preparation, data collection and image analysis steps; the samples and
grid preparation can be of unpredictable quality, there are many different
protocols for microscope and camera settings, and there is a myriad of software
programs for analysis that can depend on dozens of settings chosen by the user.
For this reason, we believe it is important to benchmark the entire workflow,
using a standard sample and standard operating procedures, on a regular basis.
This provides confidence that all aspects of the pipeline are capable of
producing maps to high resolution. Here we describe benchmarking procedures using
a test sample, rabbit muscle aldolase.
PMID- 29951481
TI - Autotaxin in Pathophysiology and Pulmonary Fibrosis.
AB - Lysophospholipid signaling is emerging as a druggable regulator of
pathophysiological responses, and especially fibrosis, exemplified by the
relative ongoing clinical trials in idiopathic pulmonary fibrosis (IPF) patients.
In this review, we focus on ectonucleotide pyrophosphatase-phosphodiesterase 2
(ENPP2), or as more widely known Autotaxin (ATX), a secreted lysophospholipase D
(lysoPLD) largely responsible for extracellular lysophosphatidic acid (LPA)
production. In turn, LPA is a bioactive phospholipid autacoid, forming locally
upon increased ATX levels and acting also locally through its receptors, likely
guided by ATX's structural conformation and cell surface associations. Increased
ATX activity levels have been detected in many inflammatory and
fibroproliferative conditions, while genetic and pharmacologic studies have
confirmed a pleiotropic participation of ATX/LPA in different processes and
disorders. In pulmonary fibrosis, ATX levels rise in the broncheoalveolar fluid
(BALF) and stimulate LPA production. LPA engagement of its receptors activate
multiple G-protein mediated signal transduction pathways leading to different
responses from pulmonary cells including the production of pro-inflammatory
signals from stressed epithelial cells, the modulation of endothelial physiology,
the activation of TGF signaling and the stimulation of fibroblast accumulation.
Genetic or pharmacologic targeting of the ATX/LPA axis attenuated disease
development in animal models, thus providing the proof of principle for
therapeutic interventions.
PMID- 29951482
TI - The Vaginal Microenvironment: The Physiologic Role of Lactobacilli.
AB - In addition to being a passage for sperm, menstruum, and the baby, the human
vagina and its microbiota can influence conception, pregnancy, the mode and
timing of delivery, and the risk of acquiring sexually transmitted infections.
The physiological status of the vaginal milieu is important for the wellbeing of
the host as well as for successful reproduction. High estrogen states, as seen
during puberty and pregnancy, promote the preservation of a homeostatic
(eubiotic) vaginal microenvironment by stimulating the maturation and
proliferation of vaginal epithelial cells and the accumulation of glycogen. A
glycogen-rich vaginal milieu is a haven for the proliferation of Lactobacilli
facilitated by the production of lactic acid and decreased pH. Lactobacilli and
their antimicrobial and anti-inflammatory products along with components of the
epithelial mucosal barrier provide an effective first line defense against
invading pathogens including bacterial vaginosis, aerobic vaginitis-associated
bacteria, viruses, fungi and protozoa. An optimal host-microbial interaction is
required for the maintenance of eubiosis and vaginal health. This review explores
the composition, function and adaptive mechanisms of the vaginal microbiome in
health and those disease states in which there is a breach in the host-microbial
relationship. The potential impact of vaginal dysbiosis on reproduction is also
outlined.
PMID- 29951484
TI - Biological and Pathological Implications of an Alternative ATP-Powered
Proteasomal Assembly With Cdc48 and the 20S Peptidase.
AB - The ATP-powered protein degradation machinery plays essential roles in
maintaining protein homeostasis in all organisms. Robust proteolytic activities
are typically sequestered within protein complexes to avoid the fatal removal of
essential proteins. Because the openings of proteolytic chambers are narrow,
substrate proteins must undergo unfolding. AAA superfamily proteins (ATPases
associated with diverse cellular activities) are mostly located at these openings
and regulate protein degradation appropriately. The 26S proteasome, comprising
20S peptidase and 19S regulatory particles, is the major ATP-powered protein
degradation machinery in eukaryotes. The 19S particles are composed of six AAA
proteins and 13 regulatory proteins, and bind to both ends of a barrel-shaped
proteolytic chamber formed by the 20S peptidase. Several recent studies have
reported that another AAA protein, Cdc48, can replace the 19S particles to form
an alternative ATP-powered proteasomal complex, i.e., the Cdc48-20S proteasome.
This review focuses on our current knowledge of this alternative proteasome and
its possible linkage to amyotrophic lateral sclerosis.
PMID- 29951485
TI - A Similar Metabolic Profile Between the Failing Myocardium and Tumor Could
Provide Alternative Therapeutic Targets in Chemotherapy-Induced Cardiotoxicity.
PMID- 29951486
TI - Screening For Pulmonary Hypertension With Multidetector Computed Tomography Among
Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve
Implantation.
AB - Aim: To assess the accuracy of multi-detector computed tomography (MDCT) derived
pulmonary vessel measurements in predicting pulmonary hypertension (PH) among
patients with severe symptomatic aortic stenosis (AS) undergoing transcatheter
aortic valve implantation (TAVI). Background: PH is common among patients with
severe AS undergoing TAVI and is associated with adverse outcomes. MDCT is the
imaging modality of choice to assess anatomical dimensions among patients
selected for TAVI. Methods: One hundred and thirty-nine patients with severe AS
undergoing TAVI with both CT scans and right heart catheterizations (RHC) were
included. CT diameters of the main pulmonary artery (MPA), right (RPA) and left
(LPA), and ascending aorta (AA) were measured. The relationship between CT
measurements and PA pressures assessing using RHC was tested with linear
regression. Results: The CT derived ratio of the diameter of the MPA to the
diameter of the AA (PA/AAratio) correlated best with mean PA pressure (R2 = 0.48)
and PA systolic pressure (R2 = 0.50). Receiver operating characteristic curve
analysis showed that the PA/AAratio is a moderate predictor of PH (AUC 0.74, 95%
CI 0.65-0.83, p < 0.0001) and that the optimal cut off point is 0.80 (sensitivity
56%, specificity 88%, positive predictive value 95.5%, negative predictive value
30.6% for PH). Conclusions: Elderly patients with severe AS and PA/AAratio values
>= 0.80 on MDCT are more likely to have PH but PH cannot be reliably excluded
among such patients with lower PA/AAratio values.
PMID- 29951487
TI - Arterial Stiffness: A Prognostic Marker in Coronary Heart Disease. Available
Methods and Clinical Application.
AB - Multiple biomarkers may predict short and long-term prognosis in patients with
coronary heart disease, but their impact is limited when used in addition to
established risk factors such blood pressure, cholesterol levels, diabetes
mellitus, smoking as well as age and sex. Arteries are an integral part of the
cardiovascular (CV) system. Arterial stiffness has been shown to be a predictor
of cardiovascular events and mortality independent of traditional risk factors.
It has also been shown that increased arterial stiffness may predict
cardiovascular events in asymptomatic individuals without overt cardiovascular
disease. Measuring arterial stiffness may, therefore, identify patients at risk
at an early stage. Antihypertensive treatment has been shown to reduce arterial
stiffness beyond its antihypertensive effect. Arterial stiffness could,
therefore, be a surrogate marker of treatment that relates to prognosis. Arterial
stiffness has mostly been used in research protocols, and its use as a prognostic
indicator in clinical practice is still uncommon. Several methods exist that can
determine parameters related to arterial stiffness, both local and in specific
artery beds such as the aorta. In this brief review we present methods to
evaluate arterial stiffness, their clinical utility, limitations and the
advantages of a novel method, the Cardio-Ankle Vascular Index. Easier and more
reproducible methods to evaluate arterial stiffness may increase the use of
parameter as a risk factor for coronary heart disease in common clinical
practice.
PMID- 29951488
TI - Advanced Atrio-Ventricular Blocks in a Foal Undergoing Surgical Bladder Repair:
First Step to Cardiac Arrest?
AB - A 3-day-old Swiss Warmblood colt was diagnosed with uroabdomen after urinary
bladder rupture. The foal had classical electrolyte abnormalities (hyponatremia,
hypochloremia and hyperkalemia) on presentation. The foal was supported prior to
surgery with intravenous fluids and the electrolyte abnormalities were treated
with physiologic saline, glucose and insulin. Urine could not be drained from the
abdomen prior to surgery because the omentum was continuously occluding the
drainage cannula and due to progressive abdominal distension, it was decided to
pursue surgery without further correction of electrolyte abnormalities. After
induction of anaesthesia, signs of hypoxemia were present. Controlled mandatory
ventilation using a pressure-controlled ventilation mode with positive end
expiratory pressure was initiated. Urine was drained from the abdomen by free
flow. Atrio-ventricular (AV) blocks unresponsive to intravenous antimuscarinic
drugs developed. After low dose of epinephrine and cardiac massage, sinus rhythm
was restored. Surgery was completed successfully and the foal recovered from
anaesthesia. The postoperative period was uneventful and the foal was discharged
from the hospital three days later. Based on a clinical case, the purpose of the
manuscript is to provide the clinician with potential causes, prevention and
treatment of this already known but rarely observed dysrhythmia which could lead
to fatal consequences. Definitions of cardiac arrest and asystole are
reappraised. We discuss the fact that advanced AV-blocks should be treated as a
cardiovascular emergency with advanced life support. The early recognition of
advanced AV blocks is the first step to reduce perioperative mortality and
morbidity of foal suffering from uroabdomen.
PMID- 29951490
TI - Increasing the Local Relevance of Epidemiological Research: Situated Knowledge of
Cattle Disease Among Basongora Pastoralists in Uganda.
AB - Cattle disease can have severe negative impacts on the livelihoods of the poor,
but still, animal disease management and outreach often remain suboptimal in low
income settings. In a study on Basongora pastoralists in Uganda, we examined
local priorities, perceptions and practices regarding cattle disease, in order to
improve outreach and disease control advisory work in such contexts. We also
investigated how participatory epidemiology can be better equipped for gathering
situated knowledge. Empirical material obtained in focus group discussions,
interviews, participatory mapping, and wealth-ranking was used to perform a
thematic, bottom-up analysis. The concepts of situated knowledge and embodied
objectivity and insights from participatory research and interdisciplinary
dialogue were applied to better embrace local perspectives. Cowdriosis,
trypanosomosis, contagious bovine pleuropneumonia, East Coast fever and anthrax
were high-priority diseases for participants. Lack of control over the animal
health situation and money invested in treatments that did not guarantee recovery
were of general importance for disease prioritization. Participants' descriptions
of diseases sometimes diverged from textbook definitions. Co-infections, chronic
and recurring infections and lack of access to formal knowledge were identified
as important factors for differences between formal and situated knowledge.
Paying attention to situated knowledge and particular context-specific issues
such as proximity to a national park proved to be of special relevance for local
understanding and experiences with disease. Another factor was the local
importance ascribed to number of cattle, rather than production levels. These
factors need to be taken into consideration when formulating disease control
advice, as does the complex disease landscape. The results reveal the importance
of moving research and advice beyond curing "knowledge-gaps" and creating
different ways of understanding disease so that situated knowledge can be
considered, and disease control improved.
PMID- 29951491
TI - Meta-analysis of the association between CD33 and Alzheimer's disease.
AB - Background: The cluster of differentiation 33 (CD33) gene is compelling among the
susceptibility genes of Alzheimer's disease (AD) in Genome-wide association study
(GWAS). Researches of the relationship between AD and polymorphism in CD33 have
showed conflicting results. In order to more precisely evaluate whether CD33
variants are associated with AD, we performed the meta-analysis presented in this
manuscript. Methods: We searched from three databases including PubMed, Cochrane
library and EMbase for related case-control researches based on criteria of
determination. A total of 18 case-control studies, containing 50,030 cases and
77,405 controls were involved in CD33 rs3865444 polymorphism. And a total of 4
case-control studies, containing 826 cases and 984 controls were involved in CD33
rs3826656 polymorphism. Results: This study demonstrated that different variants
in CD33 were associated with AD (rs3865444: OR =0.94; 95% CI, 0.90-0.98, P<0.01;
rs3826656: OR =0.94; 95% CI, 0.62-1.41, P<0.01). We made subgroup analysis which
was stratified by race. There were protective associations in Caucasians but not
in Asians among CD33 rs3865444 polymorphism (Caucasians: OR =0.92; 95% CI, 0.90
0.94, P=0.05; Asians: OR =0.87; 95% CI, 0.65-1.17, P<0.01). Conclusions: The CD33
rs3865444 polymorphism could be a protective factor in AD. Meanwhile, there was
no association between the CD33 rs3826656 polymorphism and AD. Further
confirmation is needed in larger and better-designed researches.
PMID- 29951489
TI - Bovine Tuberculosis in Britain and Ireland - A Perfect Storm? the Confluence of
Potential Ecological and Epidemiological Impediments to Controlling a Chronic
Infectious Disease.
AB - Successful eradication schemes for bovine tuberculosis (bTB) have been
implemented in a number of European and other countries over the last 50 years.
However, the islands of Britain and Ireland remain a significant aberration to
this trend, with the recent exception of Scotland. Why have eradication schemes
failed within these countries, while apparently similar programs have been
successful elsewhere? While significant socio-economic and political factors have
been discussed elsewhere as key determinants of disease eradication, here we
review some of the potential ecological and epidemiological constraints that are
present in these islands relative to other parts of Europe. We argue that the
convergence of these potential factors may interact additively to diminish the
potential of the present control programs to achieve eradication. Issues
identified include heterogeneity of diagnostic testing approaches, the presence
of an abundant wildlife reservoir of infection and the challenge of sustainably
managing this risk effectively; the nature, size, density and network structure
of cattle farming; potential effects of Mycobacterium bovis strain heterogeneity
on disease transmission dynamics; possible impacts of concurrent endemic
infections on the disclosure of truly infected animals; climatological
differences and change coupled with environmental contamination. We further argue
that control and eradication of this complex disease may benefit from an
ecosystem level approach to management. We hope that this perspective can
stimulate a new conversation about the many factors potentially impacting bTB
eradication schemes in Britain and Ireland and possibly stimulate new research in
the areas identified.
PMID- 29951492
TI - The expression of KATP channel subunits in alpha-synuclein-transfected MES23.5
cells.
AB - Background: SUR1, one of the subunits of ATP-sensitive potassium (KATP) channels,
was found to be highly expressed in mRNA levels in the substantia nigra (SN) of
Parkinson's disease (PD) brains. Though the mechanism of the selective dopamine
(DA) neurons death is still unknown, some studies have demonstrated that
selective activation of the KATP channels in the SN might be associated with the
degeneration of DA neurons. The objective of our study is to examine the
expressions of KATP channel subunits in dopaminergic cells with alpha-synuclein
(alpha-Syn) transfection. Methods: In this study, we detected the KATP channel
subunits mRNA levels in MES23.5 cells by real-time quantitative PCR after the
cells transfected with alpha-Syn. Results: Our results showed that the mRNA
levels of SUR1 subunit were markedly increased by 35% in WT alpha-Syn
overexpression cells and by 31% in A53T alpha-Syn overexpression cells,
respectively. However, the mRNA levels of SUR2B and Kir6.2 subunit have no
obviously differences from the controls. Conclusions: We showed that the mRNA
levels of SUR1 but not SUR2B or Kir6.2 were selectively upregulated in MES23.5
cells over-expressed with alpha-Syn. The findings demonstrated that the SUR1
overexpressed might be involved in the process of PD.
PMID- 29951493
TI - The impact of GAB2 genetic variations on cerebrospinal fluid markers in
Alzheimer's disease.
AB - Background: Growth factor receptor-bound protein-associated binding protein 2
gene (GAB2) has been regarded as one of the susceptibility gene associated with
Alzheimer's disease (AD). However, the role of GAB2 polymorphisms on
cerebrospinal fluid (CSF) proteins in AD continuum remains unclear. Methods: We
evaluated the connection between four single nucleotide polymorphisms (SNPs) of
GAB2 and AD-related CSF biomarkers including amyloid beta (Abeta), total tau (T
tau) and phosphorylated tau (P-tau) level in 627 Alzheimer's Disease Neuroimaging
Initiative (ADNI) subjects. Results: rs1385600 and rs1007837 were significantly
associated with all the three biomarkers in CSF (rs1385600: Abeta Pc =0.0112, T
tau Pc =0.0356, P-tau Pc =0.0116; rs1007837: Abeta Pc =0.0058, T-tau Pc =0.0278,
P-tau Pc =0.0231). rs2373115 only showed significant association with Abeta and P
tau (Abeta, Pc=0.0398, P-tau, Pc=0.0329). rs10793294 showed no significant
association with all the three biomarkers. Conclusions: Our study suggested that
GAB2 variants were significantly associated with the level of the three CSF
biomarkers, which further supported that GAB2 genetic variation modulates AD risk
via the alteration of both Abeta and tau pathology.
PMID- 29951495
TI - Characterization of the locomotor activities of zebrafish larvae under the
influence of various neuroactive drugs.
AB - Background: Behavioral changes in animals reflect functional changes in their
central nervous system. Neuroactive drugs that act on different neural pathways
can induce specific behavioral responses; therefore, it is possible to infer the
activities of neuroactive drugs by studying the behavioral changes induced by
drugs of interest in animals. Methods: In this study, AB strain zebrafish larvae
at 7 days post fertilization (dpf) were treated with different concentrations of
drugs that act on different neural pathways. Changes in the swimming distances of
zebrafish larvae under different illumination conditions and the differences in
locomotor activities between light and dark conditions (lighting motor index)
were analyzed. Results: Among the drugs studied, different concentrations of
sulpiride had no effect on larval locomotor activity either under light or dark
conditions. Progressively decreased spontaneous movements were observed in
zebrafish larvae treated with increasing doses of MK-801 and valproic acid. With
increasing concentrations of pentylenetetrazole and yohimbine, the spontaneous
movement of larval zebrafish presented a bell-shaped response. When the
illumination changed from light to dark, zebrafish larvae not treated with drugs
demonstrated increased locomotor activities. However, high levels of yohimbine,
pentylenetetrazole decreased the degree of change in the lighting motor index.
Conclusions: In conclusion, drugs that affect different neural pathways exert
different influences on the locomotor activities of zebrafish larvae. This study
presents an initial effort to establish a framework that correlates the drug
activities and the behavioral responses of zebrafish larvae under drug
treatments, which may provide a potential identification of the pathways of novel
drugs with neurological activities through their behavioral influences.
PMID- 29951494
TI - Association of lectin-like oxidized low density lipoprotein receptor 1 (OLR1)
polymorphisms with late-onset Alzheimer disease in Han Chinese.
AB - Background: Lectin-like oxidized low density lipoprotein receptor 1 (OLR1)
locates within the area of chromosome 12p, which has been identified as the AD
susceptible region, and plays a role in lipid metabolism. Therefore, it has been
suggested to be a good candidate gene for Alzheimer's disease (AD). Several SNPs
within OLR1 have been reported to have association with AD among Caucasians.
Methods: We selected and genotyped three SNPs (rs1050283, rs1050286, rs17808009)
in OLR1 to investigate its possible relationship with the onset of late-onset
Alzheimer disease(LOAD) in 984 LOAD cases and 1,354 healthy controls among
northern Han Chinese. Results: No significant association was found between the
OLR1 (rs1050283, rs1050286, rs17808009) polymorphisms and LOAD, even after
adjustment for gender and age and stratification for apolipoprotein E (APOE)
status. Conclusions: Our study showed that the SNPs (rs1050283, rs1050286,
rs17808009) located in the 3'UTR of OLR1 may not involve in the mechanism of LOAD
in Han Chinese population.
PMID- 29951496
TI - Adult-onset Krabbe disease in two generations of a Chinese family.
AB - Background: Krabbe disease (KD) is a rare autosomal recessive lysosomal storage
disorder caused by deficiency of the galactocerebrosidase (GALC) enzyme. The
adult-onset KD is infrequent, and often presenting with slowly progressive
spastic paraplegia. Herein, we describe a two-generation concomitant Chinese
pedigree of adult-onset KD in which the proband presented with acute hemiplegia
at onset. Methods: We collected the clinical and neuroimaging data of the
pedigree. GALC enzyme activity detection and gene analysis were performed to
confirm the diagnosis. Moreover, we reviewed all studies available on PubMed to
understand the correlationship between phenotype and genotype of the identified
mutations. Results: The proband presented with sudden-onset weakness of left
limbs with selective pyramidal tract involvement on diffusion-weighted imaging
(DWI) of brain MRI. The GALC enzyme activity of him was low, and the GALC gene
analysis revealed compound heterozygous pathogenic mutations of c.1901T>C and
c.1901delT. More interestingly, the homozygous c.1901T>C mutations were found in
the proband's asymptomatic father and two paternal uncles. Meanwhile, the
literature review revealed the c.1901T>C mutation was only found in the late
onset form of KD. Conclusions: These observations, combined with previous
reports, indicate that KD should be considered in the adult patients presenting
selective pyramidal tract impairment even with sudden onset.
PMID- 29951497
TI - Tau in neurodegenerative disease.
AB - Tau, a microtubule-associated protein, is the main component of the intracellular
filamentous inclusions that are involved in neurodegenerative diseases known as
tauopathies, including Alzheimer disease (AD), frontotemporal dementia with
parkinsonism-17 (FTDP-17), Pick disease (PiD), progressive supranuclear palsy
(PSP) and corticobasal degeneration (CBD). Hyperphosphorylated, aggregated tau
proteins form the core of neurofibrillary tangles (NFTs), which are shown to be
one of the pathological hallmarks of AD. The discovery of mutations in the
microtubule-associated protein tau (MAPT) gene in patients with FTDP-17 also
contributes to a better understanding of the dysfunctional tau as a cause of
diseases. Although recent substantial progress has been made in the tau pathology
of tauopathies, the mechanisms underlying tau-induced neurodegeneration remain
unclear. Here, we present an overview of the biochemical properties of tau
protein and the pathogenesis underlying tau-induced neurodegenerative diseases.
Meanwhile, we will discuss the tau-related biomarkers and ongoing tau-targeted
strategies for therapeutic modulation.
PMID- 29951499
TI - Innate immune activation in Alzheimer's disease.
AB - Alzheimer's disease (AD) is known as the most predominant cause of dementia among
the aged people. Previously, two hallmarks of AD pathology including
extracellular amyloid-beta (Abeta) deposition and neurofibrillary tangles (NFTs)
inside neurons have been identified. With a better understanding of this disease,
neuroinflammation has been a focus, and as its initial event, innate immune
activation plays an indispensable role. In brain, as an endogenous stimulator,
extracellular Abeta deposition activates innate immunity through binding to the
pattern recognition receptors (PRR), thus leading to the production and release
of substantial inflammatory mediators (NO and ROS) and cytokines (IL-1beta, IL
10, IL-33 and TNF-alpha) contributing to the development of AD. Epidemiologic
evidence has suggested an affirmative influence of non-steroidal anti
inflammatory drugs (NSAIDs) on delaying the progression of AD. Therefore,
blocking the inflammatory process may be an effective way to delay or even cure
AD. In this review, we mainly elucidate the mechanism underlying these immune
responses in AD pathogenesis and attempt to seek the therapeutic methods
targeting neuroinflammation.
PMID- 29951501
TI - Resection of esophageal diverticulum through uniportal video-assisted
thoracoscopic surgery.
AB - Open surgery remains the standard strategy for management of esophageal
diverticulum in symptomatic patients. However, in the last years an increasing
number of minimally invasive approaches have been proposed for this issue in
order to reduce the surgical trauma and favor a fast return to daily activity.
Herein, we describe a novel technique as uniportal video-assisted thoracoscopic
surgery (VATS) for performing resection of esophageal diverticulum. This
procedure was successfully carried out in three consecutive patients with giant
mid-esophageal diverticulum (mean size: 6.5+/-0.5 cm). The mean post-operative
time was 121+/-10 minutes. The chest drain was removed 48 hours later in all
cases and the mean length of hospital stay was 9+/-1 days. No intraoperative
neither postoperative complications were found in all patients but one. He had a
small fistula 15 days later that was successfully treated with stent insertion.
No recurrence of diverticulum was seen in all cases. Uniportal VATS is a feasible
procedure that in theory could reduce the surgical trauma compared to standard
open approach. However, future prospective studies should corroborate our
impression before it can be recommended as acceptable therapy.
PMID- 29951500
TI - The role of UNC5C in Alzheimer's disease.
AB - Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease in
adults characterized by the deposition of extracellular plaques of beta-amyloid
protein (Abeta), intracellular neurofibrillary tangles (NFTs), synaptic loss and
neuronal apoptosis. AD has a strong and complex genetic component that involving
into multiple genes. With recent advances in whole-exome sequencing (WES) and
whole-genome sequencing (WGS) technology, UNC5C was identified to have
association with AD. Emerging studies on cell and animal models identified that
aberrant UNC5C may contribute to AD by activating death-associated protein kinase
1 (DAPK1) which is a new component involved in AD pathogenesis with an extensive
involvement in aberrant tau, Abeta and neuronal apoptosis/autophagy. In this
review, we briefly summarize the biochemical properties, genetics, epigenetics,
and the speculative role of UNC5C in AD. We hope our review would bring
comprehensive understandings of AD pathogenesis and provide new therapeutic
targets for AD.
PMID- 29951498
TI - Microglial priming in Alzheimer's disease.
AB - Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease
of central nervous system (CNS). Nowadays, increasing evidence suggests that
immune system plays a significant role in the mechanisms of AD's onset and
progression. Microglia, the main participator in the immune system of CNS, is
always regarded as a protector of our brain in a healthy state and also has a
beneficial role in maintaining the homeostasis of CNS microenvironment. However,
chronic and sustained stimulation can push microglia into the state termed
priming. Primed microglia can induce the production of amyloid beta (Abeta), tau
pathology, neuroinflammation and reduce the release of neurotrophic factors,
resulting in loss of normal neurons in quantity and function that has immense
relationship with AD. The therapeutic strategies mainly aimed at modulating the
microenvironment and microglial activity in CNS to delay progression and
alleviate pathogenesis of AD. Overall, in this review, we highlight the mechanism
of microglial priming, and discuss the profound relationship between microglial
priming and AD. Besides, we also pay attention to the therapeutic strategies
targeting at microglial priming.
PMID- 29951502
TI - A Six-Sigma approach for comparing diagnostic errors in healthcare-where does
laboratory medicine stand?
PMID- 29951503
TI - Physical exercise and migraine: for or against?
PMID- 29951504
TI - Instrumental variable analysis in the presence of unmeasured confounding.
AB - Observational studies are prone to bias due to confounding either measured or
unmeasured. While measured confounding can be controlled for with a variety of
sophisticated methods such as propensity score-based matching, stratification and
multivariable regression model, the unmeasured confounding is usually cumbersome,
leading to biased estimates. In econometrics, instrumental variable (IV) is
widely used to control for unmeasured confounding. However, its use in clinical
researches is generally less employed. In some subspecialties of clinical
medicine such as pharmacoepidemiological research, IV analysis is increasingly
used in recent years. With the development of electronic healthcare records, more
and more healthcare data are available to clinical investigators. Such kind of
data are observational in nature, thus estimates based on these data are subject
to confounding. This article aims to review several methods for implementing IV
analysis for binary and continuous outcomes. R code for these analyses are
provided and explained in the main text.
PMID- 29951505
TI - Aortic valve replacement in young patients: should the biological prosthesis be
recommended over the mechanical?
PMID- 29951506
TI - The choice of heart valve prosthesis for aortic valve replacement in the young:
about choices and consequences.
PMID- 29951507
TI - Bioprosthetic aortic valve replacement: a telltale from the young.
PMID- 29951508
TI - Can we exonerate GLP-1 receptor agonists from blame for adverse pancreatic
events?
PMID- 29951509
TI - Translating patient related outcome measures into practice-lessons to be learnt.
PMID- 29951510
TI - Does continuous glucose monitoring during pregnancy improve glycaemic and health
outcomes in women with type 1 diabetes?-what the CONCEPTT trial adds.
PMID- 29951511
TI - Improved outcome of bilateral compared to single internal thoracic artery
grafting: patient's selection or technical skill?
PMID- 29951512
TI - Untangling the bilateral versus single internal mammary coronary artery bypass
grafting debate.
PMID- 29951513
TI - BPI fold-containing family a member 2 as a biomarker of acute kidney injury-close
but no (clinical) cigar?
PMID- 29951514
TI - Pioglitazone and cardiovascular risk in T2DM patients: is it good for all?
PMID- 29951515
TI - AdDIT Editorial comment-challenges in medication treatment of renal and
cardiovascular diseases and risk factors in adolescents with type 1 diabetes.
PMID- 29951516
TI - The role of glucagon-like peptide-1 receptor agonists in cardiovascular disease
prevention in type 2 diabetes mellitus: evidence from the most recent clinical
trials.
PMID- 29951517
TI - Anti-diabetic agents and heart health: how to use new diabetes medications in a
global strategy for the prevention of cardiovascular complications in type 2
diabetes.
PMID- 29951518
TI - LAMP assays of Zika virus and other infectious agents will inevitably see
expanded use due to their simplicity, sensitivity, specificity, and economy.
PMID- 29951519
TI - Positive correlation between TZAP and TERT in most cancers: a new player in
cancer diseases.
PMID- 29951520
TI - Sex and racial disparities in fractional flow reserve-guided percutaneous
coronary intervention utilization: a 5-year national experience.
PMID- 29951521
TI - Advancing Genomics for Drug Development and Safety Evaluation.
PMID- 29951522
TI - Overexpression of a New Zinc Finger Protein Transcription Factor OsCTZFP8
Improves Cold Tolerance in Rice.
AB - Cold stress is one of the most important abiotic stresses in rice. C2H2 zinc
finger proteins play important roles in response to abiotic stresses in plants.
In the present study, we isolated and functionally characterized a new C2H2 zinc
finger protein transcription factor OsCTZFP8 in rice. OsCTZFP8 encodes a C2H2
zinc finger protein, which contains a typical zinc finger motif, as well as a
potential nuclear localization signal (NLS) and a leucine-rich region (L-box).
Expression of OsCTZFP8 was differentially induced by several abiotic stresses and
was strongly induced by cold stress. Subcellular localization assay and yeast one
hybrid analysis revealed that OsCTZFP8 was a nuclear protein and has
transactivation activity. To characterize the function of OsCTZFP8 in rice, the
full-length cDNA of OsCTZFP8 was isolated and transgenic rice with overexpression
of OsCTZFP8 driven by the maize ubiquitin promoter was generated using
Agrobacterium-mediated transformation. Among 46 independent transgenic lines, 6
single-copy homozygous overexpressing lines were selected by Southern blot
analysis and Basta resistance segregation assay in both T1 and T2 generations.
Transgenic rice overexpressing OsCTZFP8 exhibited cold tolerant phenotypes with
significantly higher pollen fertilities and seed setting rates than nontransgenic
control plants. In addition, yield per plant of OsCTZFP8-expressing lines was
significantly (p < 0.01) higher than that of nontransgenic control plants under
cold treatments. These results demonstrate that OsCTZFP8 was a C2H2 zinc finger
transcription factor that plays an important role in cold tolerance in rice.
PMID- 29951523
TI - Fractal Dimension Analysis of Texture Formation of Whey Protein-Based Foods.
AB - Whey protein in the form of isolate or concentrate is widely used in food
industries due to its functionality to form gel under certain condition and its
nutritive value. Controlling or manipulating the formation of gel aggregates is
used often to evaluate food texture. Many researchers made use of fractal
analysis that provides the quantitative data (i.e., fractal dimension) for
fundamentally and rationally analyzing and designing whey protein-based food
texture. This quantitative analysis is also done to better understand how the
texture of whey protein-based food is formed. Two methods for fractal analysis
were discussed in this review: image analysis (microscopy) and rheology. These
methods, however, have several limitations which greatly affect the accuracy of
both fractal dimension values and types of aggregation obtained. This review
therefore also discussed problem encountered and ways to reduce the potential
errors during fractal analysis of each method.
PMID- 29951524
TI - Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic
Castration-Resistant Prostate Cancer: A Systematic Review and Indirect
Comparison.
AB - Recently, several drugs have been introduced for the first-line treatment of
chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but
few studies have compared treatment outcomes directly. This indirect comparison
among 10 clinical trials (n = 4870 patients) retrieved from PubMed, Web of
Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess
the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and
sipuleucel-T for the initial treatment of mCRPC. No significant differences in
primary outcome (overall survival) were found among initial treatments. However,
docetaxel had the highest probability (37.53%) of being the most effective, but
at the cost of more adverse events, while enzalutamide was associated with the
best secondary outcomes (prostate-specific antigen response, progression-free
survival, quality of life, and adverse event profile). Thus, docetaxel is
recommended as the first agent used for the chemotherapy of mCRPC, while
enzalutamide is recommended as the first nonchemotherapy treatment. Additional
clinical trials are needed to confirm these findings and establish the optimal
order for multidrug treatment of mCRPC.
PMID- 29951525
TI - Chronic Apical and Nonapical Right Ventricular Pacing in Patients with High-Grade
Atrioventricular Block: Results of the Right Pace Study.
AB - Objective: The aim of the study was to compare the two approaches to chronic
right ventricular pacing currently adopted in clinical practice: right
ventricular apical (RVA) and non-RVA pacing. Background: Chronic RVA pacing is
associated with an increased risk of atrial fibrillation, morbidity, and even
mortality. Non-RVA pacing may yield more physiologic ventricular activation and
provide potential long-term benefits and has recently been adopted as standard
procedure at many implanting centers. Methods: The Right Pace study was a
multicenter, prospective, single-blind, nonrandomized trial involving 437
patients indicated for dual-chamber pacemaker implantation with a high percentage
of RV pacing. Results: RV lead-tip target location was the apex or the
interventricular septum. RVA (274) and non-RVA patients (163) did not differ in
baseline characteristics. During a median follow-up of 19 months (25th-75th
percentiles, 13-25), 17 patients died. The rates of the primary outcome of death
due to any cause or hospitalization for heart failure were comparable between the
groups (log-rank test, p = 0.609), as were the rates of the composite of death
due to any cause, hospitalization for heart failure, or an increase in left
ventricular end-systolic volume >= 15% as compared with the baseline evaluation
(secondary outcome, p = 0.703). After central adjudication of X-rays, comparison
between adjudicated RVA (239 patients) and non-RVA (170 patients) confirmed the
absence of difference in the rates of primary (p = 0.402) and secondary (p =
0.941) outcome. Conclusions: In patients with indications for dual-chamber
pacemaker who require a high percentage of ventricular stimulation, RVA or non
RVA pacing resulted in comparable outcomes. This study is registered with
ClinicalTrials.gov (identifier: NCT01647490).
PMID- 29951526
TI - Determination of Microalgal Lipid Content and Fatty Acid for Biofuel Production.
AB - Biofuels produced from microalgal biomass have received growing worldwide
recognition as promising alternatives to conventional petroleum-derived fuels.
Among the processes involved, the downstream refinement process for the
extraction of lipids from biomass greatly influences the sustainability and
efficiency of the entire biofuel system. This review summarizes and compares the
current techniques for the extraction and measurement of microalgal lipids,
including the gravimetric methods using organic solvents, CO2-based solvents,
ionic liquids and switchable solvents, Nile red lipid visualization method, sulfo
phospho-vanillin method, and the thin-layer chromatography method. Each method
has its own competitive advantages and disadvantages. For example, the organic
solvents-based gravimetric method is mostly used and frequently employed as a
reference standard to validate other methods, but it requires large amounts of
samples and is time-consuming and expensive to recover solvents also with low
selectivity towards desired products. The pretreatment approaches which aimed to
disrupt cells and support subsequent lipid extraction through bead beating,
microwave, ultrasonication, chemical methods, and enzymatic disruption are also
introduced. Moreover, the principles and procedures for the production and
quantification of fatty acids are finally described in detail, involving the
preparation of fatty acid methyl esters and their quantification and composition
analysis by gas chromatography.
PMID- 29951527
TI - SWATHHM-Based Metabolomics of Follicular Fluid in Patients Shows That
Progesterone Adversely Affects Oocyte Quality.
AB - Objective: We reveal the relationship between progesterone level in follicular
fluid and oocyte quality based on sequential window acquisition of all
theoretical fragment-ion spectra (SWATHTM), a powerful high-resolution mass
spectrometric data independent acquisition technique. Method: Follicular fluid
samples were collected from 22 subjects (the level of progesterone > 1.5 ng/mL)
of progesterone group, as well as from 22 subjects (the level of progesterone <
1.5 ng/mL) of control group, and analyzed using UPLC-Q-TOF. All methods were
performed in accordance with ISO 9001:2008. Novel SWATH acquisition mode on an
ultra-high performance liquid chromatography coupled with hybrid triple
quadrupole time-of-flight mass spectrometry (with resolving power 20,000-40,000)
was investigated for the analysis of human follicular fluid. The principal
component variable grouping detects intersample variable correlation and groups
variables with similar profiles which simplifies interpretation and highlights
related ions and fragments. It can also extract product ion spectra from the data
collected by fragmenting a wide precursor ion window. Results: Follicular fluid
from the two groups differed with respect to five metabolites. Follicular fluid
from the progesterone group contained elevated levels of 8-hydroxyguanosine and 4
hydroxynonenal and reduced levels of ATP, estradiol, and L-carnitine. The
increased progesterone level on the day of HCG injection could negatively impact
oocyte quality, thus reducing the pregnancy rate of IVF patients.
PMID- 29951528
TI - Recent Development of Nuclear Molecular Imaging in Thyroid Cancer.
AB - Therapies targeting specific tumor pathways are easy to enter the clinic. To
monitor molecular changes, cellular processes, and tumor microenvironment,
molecular imaging is becoming the key technology for personalized medicine
because of its high efficacy and low side effects. Thyroid cancer is the most
common endocrine malignancy, and its theranostic radioiodine has been widely used
to diagnose or treat differentiated thyroid cancer. This article summarizes
recent development of molecular imaging in thyroid cancer, which may accelerate
the development of personalized thyroid cancer therapy.
PMID- 29951529
TI - Muscle Shortening and Spastic Cocontraction in Gastrocnemius Medialis and
Peroneus Longus in Very Young Hemiparetic Children.
AB - Objectives: Muscle shortening and spastic cocontraction in ankle plantar flexors
may alter gait since early childhood in cerebral palsy (CP). We evaluated
gastrosoleus complex (GSC) length, and gastrocnemius medialis (GM) and peroneus
longus (PL) activity during swing phase, in very young hemiparetic children with
equinovalgus. Methods: This was an observational, retrospective, and monocentric
outpatient study in a pediatric hospital. Ten very young hemiparetic children
(age 3 +/- 1 yrs) were enrolled. These CP children were assessed for muscle
extensibility (Tardieu scale XV1) in GSC (angle of arrest during slow-speed
passive ankle dorsiflexion with the knee extended) and monitored for GM and PL
electromyography (EMG) during the swing phase of gait. The swing phase was
divided into three periods (T1, T2, and T3), in which we measured a cocontraction
index (CCI), ratio of the Root Mean Square EMG (RMS-EMG) from each muscle during
that period to the peak 500 ms RMS-EMG obtained from voluntary plantar flexion
during standing on tiptoes (from several 5-second series, the highest RMS value
was computed over 500 ms around the peak). Results: On the paretic side: (i) the
mean XV1-GSC was 100 degrees (8 degrees ) (median (SD)) versus 106 degrees (3
degrees ) on the nonparetic side (p = 0.032, Mann-Whitney); (ii) XV1-GSC
diminished with age between ages of 2 and 5 (Spearman, rho = 0.019); (iii) CCIGM
and CCIPL during swing phase were higher than on the nonparetic side (CCIGM, 0.32
(0.20) versus 0.15 (0.09), p < 0.01; CCIPL, 0.52 (0.30) versus 0.24 (0.17), p <
0.01), with an early difference significant for PL from T1 (p = 0.03).
Conclusions: In very young hemiparetic children, the paretic GSC may rapidly
shorten in the first years of life. GM and PL cocontraction during swing phase
are excessive, which contributes to dynamic equinovalgus. Muscle extensibility
(XV1) may have to be monitored and preserved in the first years of life in
children with CP. Additional measurements of cocontraction may further help
target treatments with botulinum toxin, especially in peroneus longus.
PMID- 29951530
TI - Current Advances on the Important Roles of Enhancer RNAs in Gene Regulation and
Cancer.
AB - Revealing the gene regulation networks governing cancer initiation and
development is necessary while it remains uncompleted. In recent years, enhancers
have been reported to be widely transcribed, resulting in the generation of
enhancer RNAs (eRNAs). Previous studies have reported that eRNAs are a subclass
of long noncoding RNAs (lncRNAs), which play a critical role in gene regulation
and cancer development. These eRNAs can promote enhancer-promoter (E-P) looping
formation by binding to other protein factors or propel expression of downstream
protein-coding gene. In this review, we have focused on the characteristics of
eRNAs and illustrated the biological function and potential mechanism of eRNAs in
regulating gene expression and cancer development.
PMID- 29951531
TI - Efficacy and Safety of Different Norepinephrine Regimens for Prevention of Spinal
Hypotension in Cesarean Section: A Randomized Trial.
AB - The aim of this paper is to evaluate the efficacy and safety of three different
norepinephrine dosing regimens for preventing spinal hypotension in cesarean
section. In this randomized double-blinded controlled study, 120 parturients
scheduled for elective section delivery under spinal anesthesia were assigned to
1 of 4 groups. In the control group, patients received saline infusion. In three
norepinephrine groups, the infusion dosage regimens were 5, 10, and 15 MUg/kg/h,
respectively. Hypotension was treated with a rescue bolus of 10 MUg
norepinephrine. The study protocol was continued until the end of surgery. The
primary outcome was the proportion of participants that underwent hypotension.
The proportion of hypotension participants was significantly reduced in the
norepinephrine groups (37.9%, 20%, and 25%, respectively) compared to that in the
control group (86.7%). However, the highest dose of norepinephrine (15 MUg/kg/h)
resulted in more hypertension episodes. In addition, blood pressure was better
maintained in the norepinephrine 5 MUg/kg/h and 10 MUg/kg/h groups than in the
control group and 15 MUg/kg/h group. No significant differences in other
hemodynamic variables, adverse effects, maternal and neonatal blood gases, or
Apgar scores were observed among the groups. In summary, for patients who undergo
cesarean delivery under spinal anesthesia, infusion of 5-10 MUg/kg/h
norepinephrine was effective to reduce hypotension incidence without significant
adverse effects on maternal and neonatal outcomes. Clinical Trial Registration
Number is ChiCTR-INR-16009452.
PMID- 29951532
TI - A Comparative Study of Three Detection Techniques for Leifsonia xyli Subsp. xyli,
the Causal Pathogen of Sugarcane Ratoon Stunting Disease.
AB - The ratoon stunting disease (RSD), caused by the bacterium Leifsonia xyli subsp.
xyli (Lxx), is one of the most economically devastating diseases impacting
sugarcane. RSD causes significant yield losses and variety degradation. Diagnosis
of RSD is challenging because it does not exhibit any discernible internal and
external symptoms. Moreover, the Lxx bacteria are very small and difficult to
isolate, cultivate, and detect. In this study, conventional polymerase chain
reaction (PCR), real-time quantitative PCR (RT-qPCR), and Lxx-loop-mediated
isothermal amplification (Lxx-LAMP) were utilized to specifically detect the
presence of Lxx pathogens in the juice from Lxx-infected sugarcane stalks and an
Lxx-pMD18-T recombinant plasmid. The results showed that Lxx was a highly
specific causal pathogen for RSD. All three techniques provided great
reproducibility, while Lxx-LAMP had the highest sensitivity. When the DNA extract
from Lxx-infected sugarcane juice was used as a template, Lxx-LAMP was 10 and 100
times more sensitive than RT-qPCR and conventional PCR, respectively. When the
Lxx-pMD18-T recombinant plasmid was used as a template, Lxx-LAMP was as sensitive
as RT-qPCR but was 10 times more sensitive than conventional PCR. Based on the
Lxx-LAMP detection system established, adding 0.4 MUM loop primers (LF/LP) can
accelerate the reaction and reduce the total time required. In addition, the
optimal amount of Bst DNA polymerase for Lxx-LAMP reactions was determined to be
6.0 U. The results provide technical support for the detection of RSD Lxx
pathogen that will help manage sugarcane RSD.
PMID- 29951533
TI - A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through
Paraoxonase and Angiopoietin-Like 3.
AB - The collected data have revealed the beneficial effects of dipeptidyl peptidase-4
(DPP-4) inhibitors on the vascular endothelium, including vildagliptin. However,
the involved mechanisms are not yet clear. In this study, Sprague-Dawley rats
were randomly divided into the following four groups: control, diabetic, diabetic
+ low-dose vildagliptin (10 mg/kg/d), and diabetic + high-dose vildagliptin (20
mg/kg/d). The diabetic model was created by feeding a high-fat diet for four
weeks and injection of streptozotocin. Then, vildagliptin groups were given oral
vildagliptin for twelve weeks, and the control and diabetic groups were given the
same volume of saline. The metabolic parameters, endothelial function, and whole
genome expression in the aorta were examined. After 12 weeks of treatment,
vildagliptin groups showed significantly reduced blood glucose, blood total
cholesterol, and attenuated endothelial dysfunction. Notably, vildagliptin may
inhibit angiopoietin-like 3 (Angptl3) and betaine-homocysteine S
methyltransferase (Bhmt) expression and activated paraoxonase-1 (Pon1) in the
aorta of diabetic rats. These findings may demonstrate the vasoprotective pathway
of vildagliptin in vivo.
PMID- 29951534
TI - Polymorphisms of TNF-alpha -308 G/A and IL-8 -251 T/A Genes Associated with
Urothelial Carcinoma: A Case-Control Study.
AB - Cigarette smoking and exposure to environmental tobacco smoke are well-known risk
factors for urothelial carcinoma (UC). We conducted a hospital-based case-control
study involving 287 UC cases and 574 cancer-free controls to investigate the
joint effects of cigarette smoking and polymorphisms of inflammatory genes on UC
risk. Tumor necrosis factor alpha (TNF-alpha) -308 G/A and interleukin-8 (IL-8)
251 T/A polymorphisms were determined using a polymerase chain reaction
restriction fragment length polymorphism method. People who had ever smoked and
those who were exposed to environmental tobacco smoke had significantly increased
UC odds ratios (ORs) of 1.65 and 1.68, respectively. Participants who had smoked
more than 18 pack-years had a significantly increased UC OR of 2.64. People who
had ever smoked and who carried the A/A genotype of the TNF-alpha -308 G/A
polymorphism had a significantly higher UC OR (10.25) compared to people who had
never smoked and who carried the G/G or G/A genotype. In addition, people who had
ever smoked and who carried the IL-8 -251 T/T genotype had a significantly
increased UC OR (3.08) compared to people who had never smoked and who carried
the T/A or A/A genotype. In a combined analysis of three major risk factors
(cumulative cigarette smoking, the TNF-alpha -308 A/A genotype, and the IL-8 -251
T/T genotype), subjects with any one, any two, and all three risk factors
experienced significantly increased UC ORs of 1.55, 2.89, and 3.77, respectively,
compared to individuals with none of the risk factors. Conclusions. Our results
indicate that the combined effects of cumulative cigarette exposure and the TNF
alpha -308 A/A genotype and/or the IL-8 -251 T/T genotype on UC OR showed a
significant dose-response relationship.
PMID- 29951535
TI - Semiautomatic Volumetry of Low Attenuation of Thoracic Aortic Plaques on Curved
Planar Reformations Using MDCT Angiographic Data with 0.5 mm Collimation.
AB - To evaluate the relationship of aortic low attenuation plaque volume (LAPV) on
multidetector computed tomography (MDCT) with the abdominal aortic aneurysm
(AAA), the coronary arterial disease (CAD, >=50% stenosis), severe (>=90%
stenosis) CAD, hypertension, and long-term (>=10 years) hypertension. Curved
planar reformations (CPR) of three segments (the ascending, the arch, and the
upper descending aorta) of the thoracic aorta were generated with attenuation
dependent color codes to measure LAPV with 0~29 HU and total noncalcified plaque
volume (TNPV) with 0~150 HU in 95 patients. Correlation coefficients were
employed to assess the impact of each LAPV and TNPV on AAA, CAD, severe CAD,
hypertension, and long-term hypertension. Each Mean LAPV/cm and TNPV/cm was
statistically greater in the aortic arch than the ascending (p < 0.001 on each)
or the proximal descending segment (p < 0.001 on each). LAPV in the aortic arch
has moderate correlations with AAA, severe CAD, and long-term hypertension (r =
0.643, 0.639, 0.662, resp.). Plaque volumes in each aortic segment can be
measured clinically and the increasing LAPV in the arch may be a significant
factor associated with the development of severe atherosclerosis underlying AAA,
severe CAD, and long-term hypertension.
PMID- 29951536
TI - Oxidation Prevents HMGB1 Inhibition on PDGF-Induced Differentiation of
Multipotent Vascular Stem Cells to Smooth Muscle Cells: A Possible Mechanism
Linking Oxidative Stress to Atherosclerosis.
AB - Atherosclerosis is considered as a multifactorial disease in terms of the
pathogenic mechanisms. Oxidative stress has been implicated in atherogenesis, and
the putative mechanisms of its action include oxidative modification of redox
sensitive signaling factors. High mobility group box 1 (HMGB1) is a key
inflammatory mediator in atherosclerosis, but if oxidized it loses its activity.
Thus, whether and how it participates in oxidative stress-induced atherosclerosis
are not clear. The current study found that exogenous HMGB1 dose-dependently
inhibited the proliferation of multipotent vascular stem cells and their
differentiation to smooth muscle cells induced by platelet-derived growth factor.
But oxidative modification impaired the activity of HMGB1 to produce the effect.
The stem cells were regarded as the source of smooth muscle cells in vascular
remodeling and neointimal hyperplasia. Therefore, the findings suggested that
HMGB1 participated in oxidative stress-induced atherosclerosis presumably by
targeting multipotent vascular stem cells.
PMID- 29951537
TI - Pruritus: From the Bench to the Bedside.
PMID- 29951538
TI - Preoperative Diagnosis and Treatment Outcomes of Incarcerated Inferiorly
Displaced Flap Tear of the Medial Meniscus: Comparison between Flap Tears with
and without Incarcerated Fragment.
AB - The purpose of this study was to compare preoperative variables and postoperative
outcomes between flap tears with and without incarceration of inferiorly
displaced fragments of medial meniscus and find distinct features of incarcerated
flap tear of medial meniscus to improve preoperative diagnosis. 79 patients who
underwent partial meniscectomy for flap tear of medial meniscus were classified
into two groups: group U, usual flap tear without incarcerated fragment; group I,
flap tear with incarcerated inferiorly displaced fragment. Patient
characteristics and preoperative variables including duration of symptom
aggravation were investigated. A comprehensive physical examination including
joint line tenderness was performed. Magnetic resonance imaging (MRI) examination
was carried out on all patients. Clinical assessments were performed with
functional scores including visual analogue scale (VAS), and radiologic
evaluation was conducted. Preoperative values and postoperative outcomes measured
at the minimum follow-up duration of 2 years were compared between the groups.
The groups did not differ significantly regarding postoperative outcomes by
functional and radiological evaluations (p > 0.05). In making preoperative
diagnosis, sensitivity of diagnosis based solely on MR images was significantly
lower in group I (68.8%) than that in group U (90.5%) (p = 0.040). The following
clinical features differed significantly between the groups: Patients in group I
had higher scores in preoperative VAS (group U = 6.6; group I = 7.7) (p = 0.011)
and shorter duration of symptom aggravation (group U = 13.8 weeks; group I = 3.9
weeks) (p < 0.001). Joint line tenderness was positive more distinctly in group I
(100%) than in group U (74.6%). If displaced flap tear was properly resected,
improved outcomes did not differ regardless of incarceration of flap tear. In
diagnosing incarcerated inferiorly displaced flap tear, sensitivity of diagnosis
based solely on MR images could be low. Distinguishing clinical findings would be
helpful in obtaining a more appropriate diagnosis.
PMID- 29951539
TI - Comprehensive Quality Control of the Regenerative Therapy Using Platelet
Concentrates: The Current Situation and Prospects in Japan.
AB - Platelet concentrates (PCs), represented by platelet-rich plasma (PRP), have been
widely applied in the fields of regenerative and aesthetic therapies. PCs'
mechanisms of action, however, are too complicated, and it is not easy to present
the whole picture; besides, clinical outcomes are hardly reproducible in many
cases. Therefore, several medically advanced countries seemingly intend to
regulate PC therapies weakly or strictly because of the increasing popularity.
Japan established laws and regulations for PC therapy in the "Act on the Safety
of Regenerative Medicine" along with the "Pharmaceuticals, Medical Devices and
Other Therapeutic Products Act" in 2014, which, to our knowledge, represent the
strictest regulatory framework for production and therapeutic use of PCs in the
world. According to these laws and regulations, PCs produced for topical use
should be prepared as cell-based medicinal products, essentially as should stem
cells, in accordance with their registered ("licensed" under actual conditions)
standard operating procedures. Nonetheless, criteria for their quality are not
standardized. In this review, we discuss the quality of PC preparations by
focusing on the basic concept and regulatory framework of regenerative medicine
in Japan. Within the new framework, PC therapy is regulated by a specific
notification and registration system, as is stem cell therapy. In comparison with
the latter, however, risk factors that hamper successful PC therapy are much
fewer. Via appropriate evaluation of patients' conditions and whole-blood samples
by simple and sensitive but not yet fully standardized assays, it is
theoretically possible that PC quality will be controlled nearly completely. In
addition to or instead of standardization of preparation protocols,
standardization of preoperative examination of individual PC preparations is an
urgent task for improving and guaranteeing the safety and efficacy of PC therapy.
PMID- 29951540
TI - Diagnosis and Treatment of Human Salmonellosis in Addis Ababa City, Ethiopia.
AB - Background: Diagnosis using reliable tools and treatment following in vitro
antimicrobial susceptibility tests are critical to proper addressing of
antibiotic-resistant Salmonella infection. Methodology: A cross-sectional study
was conducted to assess the practice of diagnosis and treatment of salmonellosis
in Addis Ababa. Tube Widal test (for blood samples only), culture, biochemical
and carbohydrate fermentation, serotyping, and antimicrobial susceptibility tests
were employed for both blood and stool samples. Results: Of all the diseases
listed in the diagnosis, nontyphoidal (n = 72, 13.71%) and typhoidal (n = 47,
8.95%) salmonellosis were the second and third common diseases. Among the 288
blood samples, almost half were positive for O, H, or both antigens. However,
only 1 (0.68%) of the positive blood samples yielded Salmonella isolate during
culture. The study demonstrated low specificity (0.68%) and positive predictive
value (48.78%) of Widal test. Conversely, the test showed 100% sensitivity and
negative predictive values. Salmonella isolates were identified from 7 (7.07%) of
99 stool samples. Two-thirds of salmonellosis suspected patients received
antibiotic treatment. However, only half of the confirmed salmonellosis patients
were treated with appropriate antibiotics. All of the isolates were susceptible
to ciprofloxacin and ceftriaxone but resistant to ampicillin. Conclusions:
Majority of the patients who participated in this study were wrongly diagnosed
using symptoms, clinical signs, and tube Widal test. Consequently, most of the
patients received inappropriate treatment.
PMID- 29951541
TI - Pharmacokinetic Interaction Study of Ketamine and Rhynchophylline in Rat Plasma
by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry.
AB - Eighteen Sprague-Dawley rats were randomly divided into three groups: ketamine
group, rhynchophylline group, and ketamine combined with rhynchophylline group (n
= 6). The rats of two groups received a single intraperitoneal administration of
30 mg/kg ketamine and 30 mg/kg rhynchophylline, respectively, and the third group
received combined intraperitoneal administration of 30 mg/kg ketamine and 30
mg/kg rhynchophylline together. After blood sampling at different time points and
processing, the concentrations of ketamine and rhynchophylline in rat plasma were
determined by the established ultra-performance liquid chromatography tandem mass
spectrometry (UPLC-MS/MS) method. Chromatographic separation was achieved using a
UPLC BEH C18 column (2.1 mm * 50 mm, 1.7 MUm) with carbamazepine as an internal
standard (IS). The initial mobile phase consisted of acetonitrile and water
(containing 0.1% formic acid) with gradient elution. Multiple reaction monitoring
(MRM) modes of m/z 238.1 -> 179.1 for ketamine, m/z 385.3 -> 159.8 for
rhynchophylline, and m/z 237.3 -> 194.3 for carbamazepine (IS) were utilized to
conduct quantitative analysis. Calibration curve of ketamine and rhynchophylline
in rat plasma demonstrated good linearity in the range of 1-1000 ng/mL (r >
0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Moreover, the
intra- and interday precision relative standard deviation (RSD) of ketamine and
rhynchophylline were less than 11% and 14%, respectively. This sensitive, rapid,
and selective UPLC-MS/MS method was successfully applied to pharmacokinetic
interaction study of ketamine and rhynchophylline after intraperitoneal
administration. The results showed that there may be a reciprocal inhibition
between ketamine and rhynchophylline.
PMID- 29951542
TI - Small but Heavy Role: MicroRNAs in Hepatocellular Carcinoma Progression.
AB - Hepatocellular carcinoma (HCC), which accounts for 85-90% of primary liver
cancer, is the fifth most common malignant tumor and the third leading cause of
cancer-related deaths worldwide, but the pathological mechanism of HCC is still
not fully elucidated. miRNAs are evolutionarily endogenous small noncoding RNAs
that negatively regulate gene expression via posttranscriptional inhibition or
target mRNA degradation in several diseases, especially human cancer. Therefore,
discovering the roles of miRNAs is appealing to scientific researchers. Emerging
evidence has shown that the aberrant expressions of numerous miRNAs are involved
in many HCC biological processes. In hepatocarcinogenesis, miRNAs with
dysregulated expression can exert their function as oncogenes or tumor
suppressors depending on their cellular target during the cell cycle, and in
tumor development, differentiation, apoptosis, angiogenesis, metastasis, and
progression of the tumor microenvironment. In this review, we summarize current
findings on miRNAs and assess their functions to explore the molecular mechanisms
of tumor progression in HCC.
PMID- 29951543
TI - Psychometric Properties of the Chinese (Putonghua) Version of the Oxford
Cognitive Screen (OCS-P) in Subacute Poststroke Patients without Neglect.
AB - Background: Oxford Cognitive Screen is designed for assessing cognitive functions
of poststroke patients. This study was aimed to assess the psychometric
properties of the Chinese (Putonghua) version of the Oxford Cognitive Screen
Putonghua (OCS-P) for use among poststroke patients without neglect. Methods:
Expert review panel evaluated content validity of the Chinese-translated items.
After pilot tested the translated items, the patients and healthy participants
completed the OCS-P as well as the Montreal Cognitive Assessment (MoCA-ChiB) and
Goldenberg's test. A group of patients completed OCS-P for the second time within
seven days. Data analyses included confirmatory factor analysis, item difficulty
and item-total correlation, inter- and intrarater reliability, internal
consistency, and between-group discrimination. Results: One hundred patients and
120 younger (n = 60) or older (n = 60) healthy participants completed all the
tests. Modifications were required for items in the "Picture Naming",
"Orientation", and "Sentence Reading" subscales. Confirmatory factor analysis
revealed a three-factor structure for the OCS-P subscales. The internal
consistency coefficients for the three identified test dimensions were 0.30 to
0.52 (Cronbach's alpha). Construct validity coefficients between the OCS-P and
MoCA-ChiB subscales were 0.45 < r < 0.79 (p < 0.001) and the "Praxis" subscale of
OCS-P and Goldenberg's test was r = 0.72 (p < 0.001). The interrater reliability
coefficients for the subscales were in general higher than the intrarater
reliability coefficients. The "Picture Naming" and "Numerical Cognition"
subscales were the most significant (p = 0.003) for differentiating patient
participants from their older healthy counterpart. Conclusion: This study
generated satisfactory evidence on the content validity, substantive validity,
construct validity, inter- and intrarater reliability, and known-group
discrimination of the OCS-P. They support its application among poststroke
patients who speak Putonghua. Future studies could review the existing five
dimension domains for improving its structural validity and internal consistency
as well as generate evidence of the OCS-P for use among the poststroke patients
with neglect.
PMID- 29951544
TI - Relationship with Parents, Emotion Regulation, and Callous-Unemotional Traits in
Adolescents' Internet Addiction.
AB - The aim of this study was to investigate the associations of relationship with
parents, emotion regulation, and callous-unemotional traits with Internet
addiction in a community sample of adolescents. Self-report measures of
relationship with parents (both mothers and fathers), emotion regulation (in its
two dimensions: cognitive reappraisal and expressive suppression), callous-
unemotional traits (in its three dimensions: callousness, uncaring, and
unemotional), and Internet addiction were completed by 743 adolescents aged 10 to
21 years. Results showed that a low perceived maternal availability, high
cognitive reappraisal, and high callousness appeared to be predictors of Internet
addiction. The implications of these findings are then discussed.
PMID- 29951545
TI - Effect of Camphorquinone Concentration in Physical-Mechanical Properties of
Experimental Flowable Resin Composites.
AB - The aim of this study was to evaluate the effect of camphorquinone concentration
in physical-mechanical properties of experimental flowable composites in order to
find the concentration that results in maximum conversion, balanced mechanical
strength, and minimum shrinkage stress. Model composites based on BISGMA/TEGDMA
with 70% wt filler loading were prepared containing different concentrations of
camphorquinone (CQ) on resin matrix (0.25%, 0.50%, 1%, 1.50%, and 2% by weight).
Degree of conversion was determined by FTIR. Surface hardness was assessed before
and after 24 h ethanol storage and softening rate was determined. Depth of cure
was determined by Knoop hardness evaluation at different depths. Color was
assessed by reflectance spectrophotometer, employing the CIE-Lab system. Flexural
strength and elastic modulus were determined by a three-point bending test.
Shrinkage stress was determined in a Universal Testing Machine in a high
compliance system. Data were submitted to ANOVA and Tukey's test (alpha = 0.05).
The increase in CQ concentration caused a significant increase on flexural
strength and luminosity of composites. Surface hardness was not affected by the
concentration of CQ. Composite containing 0.25% wt CQ showed lower elastic
modulus and shrinkage stress when compared to others. Depth of cure was 3 mm for
composite containing 1% CQ and 2 mm for the other tested composites. Degree of
conversion was inversely correlated with softening rate and directly correlated
with elastic modulus and shrinkage stress. In conclusion, CQ concentration
affects polymerization characteristics and mechanical strength of composites. The
concentration of CQ in flowable composite for optimized polymerization and
properties was 1% wt of the resin matrix, which allows adequate balance among
degree of conversion, depth of cure, mechanical properties, and color
characteristics of these materials.
PMID- 29951546
TI - Time Trends and Regional Variation in Prevalence of Asthma and Associated Factors
in Saudi Arabia: A Systematic Review and Meta-Analysis.
AB - Background: Asthma is the most common reason for emergency visits to hospital and
loss of productive hours. In Saudi Arabia, asthma affects more than 2 million
people and majority of them have uncontrolled asthma with their quality of life
adversely being impacted. It is well known that the prevalence of asthma has been
increasing in many places around the world in the last few decades. The present
review attempted to identify studies on asthma and associated factors in Saudi
Arabian population and assess their time trends and regional variation. Methods:
The titles and abstracts of retrieved articles were compared to delete
duplication and irrelevant data. A data collection form was designed to extract
several key components from selected articles like bibliographic information on
the article, study population, and sample size. Extracted information was grouped
appropriately for data analysis. Database search retrieved 71 articles. Applying
inclusion and exclusion criteria, 40 articles were excluded and 31 qualified full
articles were included for the review. Results: Among 31 retained studies, Riyadh
had the highest publication output followed by Jeddah. Ten studies were based on
ISAAC and 5 on non-ISAAC questionnaires while 5 studies were genetic studies
conducted to unravel the genetic basis of asthma. Most of the studies were
conducted on pediatric subjects of less than 16 years of age. Sample sizes ranged
from less than 150 to more than 10000 with study settings being predominantly
urban (22 studies). The pooled weighted prevalence rates of asthma, lifetime
wheeze, and rhinitis were 14.3% (95% CI: 13.4-15.2), 16.5 (95% CI 15.5-17.4), and
21.4 (95% CI 20.5-22.3), respectively. An increase in asthma prevalence from 1990
to 2000 along with a stabilized or not so significant decline in the prevalence
from 2010 to 2016 was observed. Conclusion: The prevalence of asthma varied in
different regions without any disparity in prevalence in the rural and urban
areas of Saudi Arabia. The understanding of genetic variability and recognition
of risk factors in asthma patients can greatly help in individualizing the
therapy for the management and control of asthma.
PMID- 29951547
TI - Prevalence of Abnormal Glucose Regulation according to Different Diagnostic
Criteria in Ischaemic Stroke without a History of Diabetes.
AB - We aimed to investigate the prevalence and distribution of abnormal glucose
regulation, including prediabetes and newly diagnosed diabetes, according to
different criteria in ischaemic stroke patients without a history of diabetes.
Data were derived from a representative cohort across China. Prediabetes was
defined as fasting plasma glucose (FPG) 5.6-6.9 mmol/L or 2-hour oral glucose
tolerance test (OGTT) 7.8-11.0 mmol/L or haemoglobin A1c (HbA1c) 5.7-6.4%. Newly
diagnosed diabetes was defined as FPG >= 7.0 mmol/L, 2 h OGTT >= 11.1 mmol/L or
HbA1c >= 6.5%. Among 1251 ischaemic stroke patients, 471 (37.5%) were detected as
prediabetes and 539 (43.1%) were detected as newly diagnosed diabetes.
Prediabetes was present in 118 (9.4%), 290 (23.2%) and 314 (25.1%) stroke
patients, and newly diagnosed diabetes was present in 138 (11.0%), 370 (29.6%),
and 365 (29.2%) stroke patients, based on FPG, 2 h OGTT, and HbA1c criteria,
respectively. Dependency on FPG alone would have missed 74.9% of patients in the
prediabetes range and 74.4% of patients in the diabetes range. Our study
demonstrated a high prevalence of prediabetes and diabetes in ischaemic stroke
patients without a history of diabetes. OGTT and HbA1c helped detect the majority
of prediabetes and newly diagnosed diabetes in ischaemic stroke patients.
PMID- 29951548
TI - A Method for Prediction of Femoral Component of Hip Prosthesis Durability due to
Aseptic Loosening by Using Coffin/Manson Fatigue Model.
AB - The purpose of this work is to develop a new model estimate of the fatigue life
of a hip prosthesis due to aseptic loosening as a multifactorial phenomenon. The
formula developed here is a three-parameter model based on Basquin's law for
fatigue, eccentric compression formula for the compressive stress and torsion in
the prosthesis due to the horizontal components of the contact force. With our
model, we can accurately predict the durability of a hip prosthesis due to the
following four parameters: body weight, femoral offset, duration, and intensity
of daily physical activities of a patient. The agreement of the prediction with
the real life of the prosthesis, observed on 15 patients, is found to be
adequate. Based on the formula derived for a particular implant, there was a high
degree of concurrence between the model-predicted and actual values of aseptic
loosening (durability) proved by the Mann-Whitney U test. By virtue of the
validated model, it is possible to predict, quantitatively, the influence of
various factors on the hip life. For example, we can conclude that a 10% decrease
of a patient's body mass, with all other conditions being the same, causes 5%
increase of the hip fatigue life.
PMID- 29951549
TI - The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium
and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology,
and Oral Health.
AB - Vitamin D plays an important role in calcium homeostasis and bone metabolism,
with the capacity to modulate innate and adaptive immune function, cardiovascular
function, and proliferation and differentiation of both normal and malignant
keratinocytes. 1,25(OH)2D, the biologically active form of vitamin D, exerts most
of its functions through the almost universally distributed nuclear vitamin D
receptor (VDR). Upon stimulation by 1,25(OH)2D, VDR forms a heterodimer with the
retinoid X receptor (RXR). In turn, VDR/RXR binds to DNA sequences termed vitamin
D response elements in target genes, regulating gene transcription. In order to
exert its biological effects, VDR signalling interacts with other intracellular
signalling pathways. In some cases 1,25(OH)2D exerts its biological effects
without regulating either gene expression or protein synthesis. Although the
regulatory role of vitamin D in many biological processes is well documented,
there is not enough evidence to support the therapeutic use of vitamin D
supplementation in the prevention or treatment of infectious, immunoinflammatory,
or hyperproliferative disorders. In this review we highlight the effects of
1,25(OH)2D on bone and calcium homeostasis, on cancer, and refer to its effects
on the cardiovascular and immune systems.
PMID- 29951550
TI - Effect of High Protein Diet and Probiotic Lactobacillus casei Shirota
Supplementation in Aflatoxin B1-Induced Rats.
AB - Probiotic Lactobacillus casei Shirota (LcS) is a potential decontaminating agent
of aflatoxin B1 (AFB1). However, few studies have investigated the influence of
diet, especially a high protein (HP) diet, on the binding of AFB1 by probiotics.
This research was conducted to determine the effect of HP diet on the ability of
LcS to bind AFB1 and reduce aflatoxin M1 (AFM1) in AFB1-induced rats. Sprague
Dawley rats were randomly divided into three groups: A (HP only), B (HP + 108 CFU
LcS + 25 MUg AFB1/kg BW), and C (HP + 25 MUg AFB1/kg BW). Levels of AST and ALP
were higher in all groups but other liver function's biomarkers were in the
normal range, and the liver's histology showed no structural changes. The urea
level of rats in group B (10.02 +/- 0.73 mmol/l) was significantly lower (p <
0.05) than that of rats in group A (10.82 +/- 0.26 mmol/l). The presence of
carcinoma in the small intestine and colon was more obvious in group C than in
group B. Moreover, rats in group B had significantly (p < 0.05) lower AFM1
concentration (0.39 +/- 0.01 ng/ml) than rats in group C (5.22 +/- 0.28 ng/ml).
Through these findings, LcS supplementation with HP diet alleviated the adverse
effects of AFB1 by preventing AFB1 absorption in the small intestine and reducing
urinary AFM1.
PMID- 29951552
TI - Characterization of the Cicatrization Process in Diabetic Foot Ulcers Based on
the Production of Reactive Oxygen Species.
AB - The present study aims at evaluating the correlation between the free radical
formation and the healing action of lower limbs' ulcers in a randomized
controlled trial with the use of an adhesive derived from natural latex
associated with a light-emitting diode (LED) circuit. The sample consists of 15
participants with lower limb lesions divided into three groups: group 1 case (5
participants) received the proposed dressing system adhesive of the natural latex
associated with the LED circuit; group 2 control (5 participants) received the
dressings at home performed by nurses according to and established by the clinic
of wounds (treated with calcium alginate or silver foam); and group 3 (5
participants) also received the dressing in their homes with the use of the
dressing adhesive derived from the natural latex associated with the LED circuit.
The collected data were analyzed qualitatively and quantitatively by electron
paramagnetic resonance for determination of free radical formation. Kruskal
Wallis statistical test was used to evaluate the effect of treatment on the lower
limb's ulcer cicatrization process and its correlation with free radical. The
results obtained corroborated the hypothesis about the reduction of the quantity
of these molecules in the end of treatment related to the healing wound.
PMID- 29951551
TI - Prevalence of Chronic Complications, Their Risk Factors, and the Cardiovascular
Risk Factors among Patients with Type 2 Diabetes Attending the Diabetic Clinic at
a Tertiary Care Hospital in Sri Lanka.
AB - Diabetes incurs heavy burden to patients and the healthcare system. Assessment of
disease burden is important in taking necessary precautions and management
decisions. We aimed to determine the prevalence of macro- and microvascular
complications, their risk factors, and coronary artery disease (CAD) risk factors
among patients with type 2 diabetes mellitus (T2DM). A descriptive cross
sectional single-centre study was carried out among 3000 patients with T2DM
attending the diabetic clinic at the National Hospital of Sri Lanka from January
to July 2016. The study population had 72.7% females and 27.3% males. Mean age
and disease duration were 58.3 +/- 10.3 and 10.8 +/- 7 years, respectively.
Prevalence of CAD, stroke, and peripheral vascular disease were 10.6%, 1.1%, and
4.7% while diabetic retinopathy, neuropathy, nephropathy, diabetic foot, and
lower extremity amputation (LEA) were 26.1%, 62.6%, 50.8%, 2.6%, and 1.3%,
respectively. Prevalence of overweight/obesity, hypertension, dyslipidemia, and
smoking were 80%, 77.6%, 76.7%, and 11%, respectively. Increased age, disease
duration, and HBA1c were risk factors for microvascular disease and diabetic foot
while age was the only risk factor for macrovascular complications. Occurrence of
CAD, peripheral neuropathy, diabetic foot, and LEA was significantly higher among
males than when compared to females. This study highlights the major burden of
chronic complications and high prevalence of CAD risk factors in this population.
PMID- 29951553
TI - Inflammatory Markers in Older Women with a History of Gestational Diabetes and
the Effects of Weight Loss.
AB - The purpose of this study was to compare systemic inflammation in older women
with a history of gestational diabetes (GDM) who developed impaired glucose
tolerance (IGT) or type 2 diabetes (T2DM) to that in those with normal glucose
tolerance (NGT) and to determine, in these women, the effect of weight loss (WL)
induced by diet and exercise training on systemic inflammation and adipokine
levels. This was a longitudinal clinical investigation of overweight/obese (BMI:
32 +/- 1 kg/m2) women (59 +/- 1 years) with a GDM history (n = 19) who had normal
glucose tolerance (NGT, n = 7) or IGT/T2DM (n = 12). Women completed 6 months of
weight loss induced by diet and exercise and underwent VO2max, body composition,
blood draw, glucose tolerance testing, and 2-hour hyperinsulinemic-euglycemic
clamps (40 mU.m-2.min-1). Glucose utilization (M) was 42% higher in the NGT group
(P < 0.05). CRP was two-fold higher in the IGT/T2DM group than that in the NGT
group (P < 0.01). Adiponectin levels were 59% higher in the NGT group than those
in the IGT/T2DM group (P < 0.01). IL-6sR was higher in the NGT group (P < 0.01).
The women lost body weight, body fat, visceral fat, and subcutaneous abdominal
fat (P < 0.001). Fasting glucose (P < 0.05), fasting insulin, glucose, and
insulin AUC decreased (all P < 0.005) after the intervention. M increased by 21%
(P < 0.05). CRP (-16%) and TNFR1 (-6%) tended to decrease, whereas TNFalpha, IL
6, SAA, and adiponectin did not change in the group. In conclusion, older women
with a history of GDM who have developed IGT or T2DM have higher CRP and reduced
adiponectin levels despite similar BMI and total and abdominal obesity to those
with NGT. Six months WL induced by diet and exercise improves body composition
and increases insulin sensitivity without a significant modification of
inflammatory markers and adiponectin levels.
PMID- 29951554
TI - Translation and Validation of the Sinhalese Version of the Brief Medication
Questionnaire in Patients with Diabetes Mellitus.
AB - Background: Adherence to long-term therapy for diabetes remains low. Accurately
measuring adherence is the primary step in improving adherence. We translated and
validated the Sinhalese version of the Brief Medication Questionnaire (BMQ) in
patients with diabetes. Methods: The study was conducted at the National Hospital
of Sri Lanka between April and December 2017, including 165 patients with
diabetes. BMQ was translated into Sinhalese using the translation-back
translation method. The translated questionnaire validation included evaluation
of internal consistency, temporal stability, and performance in regard to a gold
standard (HbA1c). Results: Mean age (+/-SD) was 60.6 +/- 11.1 years, and 46.1%
were males. Mean duration of diabetes in the participants was 13.4 +/- 7.8 years.
Mean HbA1c was 8.3 +/- 1.7%, with poor glycaemic control (HbA1c >= 8.5%)
identified in 41.8%. Medication adherence measured by the BMQ regimen, belief,
and recall screens were 39.4%, 75.8%, and 18.8%, respectively. In the analysis of
temporal stability, the overall BMQ and the regimen, belief, and recall screens
demonstrated good concordance between test and retest with significant gamma
correlation coefficients of r = 0.85 (p < 0.001), r = 0.81 (p < 0.001), r = 0.84
(p < 0.001), and r = 0.91 (p < 0.001), respectively. The overall BMQ had a
Cronbach alpha coefficient of 0.65 (95% CI: 0.61-0.70). The questionnaire
performance with regards to the gold standards for the overall BMQ AUC was 0.73
(95% CI 0.65-0.80), while the BMQ regimen screen AUC was 0.61 (95% CI 0.53-0.70).
The overall BMQ score with a cutoff value of 2 presented better equilibrium
between sensitivity and specificity for the gold standard. Those with low
adherence had a significantly higher percentage of poor glycaemic control (HbA1c
>= 8.5%). Conclusion: The translated questionnaire demonstrated good reliability
(internal consistency), temporal stability (test-retest reliability), and
validity when assessed using a gold standard for disease control. Using
culturally validated tools to evaluate adherence may help clinicians to identify
low adherence and institute corrective measures.
PMID- 29951555
TI - Postload Glycated Albumin as an Alternate Measure for Diabetes Screening in a
Chinese Population.
AB - In previous epidemiological screening in China, glycated albumin (GA) was mostly
detected during the fasting state. This strict restriction causes some problems
with diabetes screening. It is unclear if GA could help improve the efficiency of
screening for diabetes for subjects who are not in the fasting state. The present
study analyzed the differences between fasting and postload (30, 60, 120, and 180
min) GA levels. A total of 691 participants were enrolled in the present study.
The Bland-Altman difference plots revealed that 95.4, 94.8, 93.6, and 93.9% of
data points were within the limits of agreement for each time point. The receiver
operating characteristic curve showed that the areas under the curve (AUC) for
baseline GA and postload GA for every time point were 0.822 (95% CI 0.791-0.849),
0.821 (95% CI 0.790-0.848), 0.833 (95% CI 0.803-0.860), 0.840 (95% CI 0.811
0.867), and 0.840 (95% CI 0.810-0.867), with sensitivities of 67.5, 68.1, 69.3,
71.6, and 69.3%, respectively. There was no difference between the baseline and
postload GA levels in either AUC or sensitivity (all p > 0.05). In conclusion,
postload serum GA levels were in good agreement with those at baseline, and thus,
it may be reasonable to employ nonfasting measurements of GA levels for diabetes
screening.
PMID- 29951556
TI - Liver HLA-E Expression Is Associated with Severity of Liver Disease in Chronic
Hepatitis C.
AB - Hepatitis C virus (HCV) can escape from innate and adaptive immunity, making the
immune response ineffective. Human leukocyte antigen E (HLA-E) might regulate the
antiviral function of immune response and contribute to the persistence of HCV
and the severity of liver disease. This study aimed to evaluate the expression of
HLA-E in the liver and its association with the severity of liver disease in HCV
patients. We performed a retrospective analysis of liver biopsies from 125 HCV
patients and from 20 control subjects without liver disease. Liver biopsies were
reviewed and classified according to severity of fibrosis and inflammatory
activity. The pathologist assessed the magnitude of HLA-E expression in a
semiquantitative way, attributing scores from 0 to 3. Immunohistochemistry showed
positive for HLA-E in hepatocyte and Kupffer cells. The rate of HLA-E positivity
in hepatocytes and Kupffer cells was significantly higher in HCV patients
compared to controls. The liver samples classified as severe fibrosis and
necroinflammatory activity presented greater expression of HLA-E on Kupffer cells
and hepatocytes, with a significant linear association. It indicates that HLA-E
expression may have an immunomodulatory effect and a possible role in the
severity of liver disease in chronic hepatitis C.
PMID- 29951557
TI - Integrin alpha9 Suppresses Hepatocellular Carcinoma Metastasis by Rho GTPase
Signaling.
AB - Integrin subunit alpha 9 (ITGA9) mediates cell-cell and cell-matrix adhesion,
cell migration, and invasion through binding different kinds of extracellular
matrix (ECM) components. However, its potential role and underlying molecular
mechanisms remain unclear in hepatocellular carcinoma (HCC). Here, we found that
ITGA9 expression was obviously decreased in patients with HCC, which was
negatively correlated with HCC growth and metastasis. ITGA9 overexpression
significantly inhibited cell proliferation and migration in vitro as well as
tumor growth and metastasis in vivo. Our data demonstrated that the inhibitory
effect of ITGA9 on HCC cell motility was associated with reduced phosphorylation
of focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src), disrupted focal
adhesion reorganization, and decreased Rac1 and RhoA activity. Our data suggest
ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness
through FAK/Src-Rac1/RhoA signaling.
PMID- 29951560
TI - Primary Bile Duct Perforation Associated with Pancreatitis.
AB - Primary bile duct perforation is rare in adults. It commonly results in biliary
peritonitis and high morbidity and mortality. We present a 72-year-old man who
was initially admitted with biochemically diagnosed pancreatitis who was found to
have a bile duct perforation and bile collection limited to the lesser sac. This
presented a diagnostic challenge and, due to its containment, did not result in
generalized biliary peritonitis, which is usually associated with this condition.
His condition was managed with stenting with endoscopic retrograde
cholangiopancreatography.
PMID- 29951558
TI - NMO-IgG and AQP4 Peptide Can Induce Aggravation of EAMG and Immune-Mediated
Muscle Weakness.
AB - Neuromyelitis optica (NMO) and myasthenia gravis (MG) are autoimmune diseases
mediated by autoantibodies against either aquaporin 4 (AQP4) or acetylcholine
receptor (AChR), respectively. Recently, we and others have reported an increased
prevalence of NMO in patients with MG. To verify whether coexisting autoimmune
disease may exacerbate experimental autoimmune MG, we tested whether active
immunization with AQP4 peptides or passive transfer of NMO-Ig can affect the
severity of EAMG. Injection of either AQP4 peptide or NMO-Ig to EAMG or to naive
mice caused increased fatigability and aggravation of EAMG symptoms as expressed
by augmented muscle weakness (but not paralysis), decremental response to
repetitive nerve stimulation, increased neuromuscular jitter, and aberration of
immune responses. Thus, our study shows increased disease severity in EAMG mice
following immunization with the NMO autoantigen AQP4 or by NMO-Ig, mediated by
augmented inflammatory response. This can explain exacerbation or increased
susceptibility of patients with one autoimmune disease to develop additional
autoimmune syndrome.
PMID- 29951559
TI - Altered birefringence of peripapillary retinal nerve fiber layer in multiple
sclerosis measured by polarization sensitive optical coherence tomography.
AB - Background: The retina has been used to study the pathophysiology of multiple
sclerosis (MS). Peripapillary retinal nerve fiber layer (pRNFL) thinning has been
suggested as an ocular biomarker of neurodegeneration in MS. The goal of this
project was to determine the birefringence of the pRNFL by measuring the fiber
birefringence using polarization sensitive optical coherence tomography (PS-OCT).
Methods: Sixty-six MS patients without history of optic neuritis (age: 39.9 +/-
11.0 yrs. old, 53 females and 13 males) and 66 age- and gender-matched normal
controls (age: 40.7 +/- 11.4 yrs. old) were recruited. Custom built PS-OCT was
used to measure phase retardation per unit depth (PR/UD, proportional to the
birefringence) and pRNFL thickness in each quadrant of the pRNFL. In addition,
clinical manifestation was used to correlate with the pRNFL birefringence.
Results: The pRNFL was thinner in the temporal and inferior quadrants in MS
patients compared with normal controls (P < 0.05). The PR/UD of the pRNFL was
significantly decreased in MS patients (P < 0.05) in all quadrants except for the
nasal quadrant. In both groups, the PR/UD from all four quadrants was not related
to the averaged pRNFL thickness (P > 0.05). In MS patients, the PR/UD was not
related to the expanded disability status scale (EDSS) nor disease duration (r
ranged from - 0.17 to 0.02, P > 0.05). Conclusion: This is the first study using
PS-OCT to study the pRNFL birefringence in MS patients. Decreased birefringence
of the pRNFL may indicate microtubule abnormality, and could be a potential
biomarker for detecting early neurodegeneration in MS.
PMID- 29951561
TI - Rare Collision Tumor of the Biliary Tract.
AB - Malignancies of the gallbladder are uncommon in the developed world. Collision
tumors are also extremely rare neoplastic phenomena. Given their scarcity, there
are no guidelines for treatment, and prognosis is based on the more aggressive
tumor type. We present a patient with a collision tumor consisting of signet-ring
cholangiocarcinoma and large-cell neuroendocrine gallbladder carcinoma of the
biliary tract, and we review the literature pertaining to biliary tract collision
tumors and their management.
PMID- 29951562
TI - Development of Drug-Induced Inverse Psoriasis in a Patient with Crohn's Disease.
AB - Crohn's disease is difficult to manage and often requires multiple medications.
While these drugs vastly improve quality of life, physicians must monitor for
adverse events. We report a case of a flare of inverse psoriasis after 15 months
of treatment with ustekinumab. This is the third reported case of a flare of drug
induced psoriasis with ustekinumab, and it is the first reported case with an
inverse presentation; however, the clinical picture is confounded by concomitant
use of hydroxychloroquine. Inverse psoriasis is a rare variant of drug-induced
psoriasis of which physicians must be cognizant while treating patients with
Crohn's disease.
PMID- 29951563
TI - Infliximab-Induced Aseptic Meningitis in a Patient with Crohn's Disease.
AB - Infliximab is an anti-tumor necrosis factor alpha (TNFalpha) monoclonal antibody
that treats moderate-to-severe Crohn's disease. In rare cases, infliximab has
been associated with drug-induced aseptic meningitis. We present a 46-year-old
woman with migraines and inflammatory Crohn's colitis treated with intravenous
infliximab and methotrexate. She developed nuchal rigidity, photophobia, and
headache 2 days after each of her infliximab infusions, with symptom resolution 1
week post-infusion. Her exam, imaging, and cerebrospinal fluid analysis were
consistent with drug-induced aseptic meningitis. She discontinued infliximab and
started vedolizumab with continued remission of her Crohn's disease.
PMID- 29951564
TI - Hemospray as the Initial Treatment of a Lower Gastrointestinal Bleed Resulting
from Stercoral Ulceration.
AB - Stercoral ulceration, an uncommon complication of constipation and fecal
impaction, can present as a significant lower gastrointestinal bleed. Endoscopic
management of this complication is rarely described in the literature. We
describe the first documented case of an individual with massive hematochezia in
the setting of stercoral ulceration being managed with Hemospray (Cook Medical,
Bloomington, Indiana).
PMID- 29951565
TI - Successful Removal of Proximally Migrated Biliary Stent in a Liver Transplant
Patient by Single-Operator Digital Cholangioscopy.
PMID- 29951566
TI - Primary Intramedullary Spinal Cord Lymphoma Presenting as a Cervical Ring
Enhancing Lesion in an AIDS Patient.
AB - Primary intramedullary spinal cord lymphoma (PISCL) is rare and constitutes only
1% of central nervous system lymphomas. We report a case of PISCL in a 37-year
old man with advanced AIDS. To our knowledge, only 4 cases of PISCL in the
setting of HIV/AIDS have been reported in the literature. Despite treatment,
prognosis remains dismal.
PMID- 29951567
TI - Hair Follicle Stem Cell Isolation and Expansion.
AB - Stem cells are widely used for numerous clinical applications including limbal
stem cell deficiency. Stem cell derived from the bulge region of the hair
follicle have the ability to differentiate into a variety of cell types including
interfollicular epidermis, hair follicle structures, sebaceous glands and corneal
epithelial cells when provided the appropriate cues. Hair follicle stem cells are
being studied as a valuable source of autologous stem cells to treat disease. The
protocol described below details the isolation and expansion of these cells for
eventual clinical application. We used a dual-reporter mouse model to visualize
both isolation and eventual differentiation of these cells in a limbal stem cell
deficient mouse model.
PMID- 29951568
TI - Osteoblast Sorting and Intracellular Staining of CXCL12.
AB - Osteoblasts are bone marrow endosteum-lining niche cells playing important roles
in the regulation of hematopoietic stem cells by secreting factors and cell
adhesion molecules. Characterization of primary osteoblasts has been achieved
through culture of outgrowth of collagenase treated bone. Immunophenotyping and
flow-based analysis of long bone osteoblasts offer a simplified and rapid
approach to characterize osteoblasts. We describe a modified procedure of
isolating mouse bone marrow osteoblastic cells based on cell surface
immunophenotyping. The chemokine CXCL12 (also known as stromal-derived factor,
SDF-1) together with its receptor CXCR4 are expressed by osteoblasts and bone
marrow stroma cells. The CXCL12-CXCR4 axis is important for hematopoietic stem
cell retention to their niches (Sugiyama et al., 2006) and for supporting
leukemia initiating cell activity (Pitt et al., 2015). Here we describe the
procedure of intracellular staining of CXCL12.
PMID- 29951569
TI - Guanine Nucleotide Exchange Assay Using Fluorescent MANT-GDP.
AB - GTPases are molecular switches that cycle between the inactive GDP-bound state
and the active GTP-bound state. GTPases exchange nucleotides either by its
intrinsic nucleotide exchange or by interaction with guanine nucleotide exchange
factors (GEFs). Monitoring the nucleotide exchange in vitro, together with
reconstitution of direct interactions with regulatory proteins, provides key
insights into how a GTPase is activated. In this protocol, we describe core
methods to monitor nucleotide exchange using fluorescent N-Methylanthraniloyl
(MANT)-guanine nucleotide.
PMID- 29951570
TI - Testing Effects of Chronic Chemogenetic Neuronal Stimulation on Energy Balance by
Indirect Calorimetry.
AB - The fundamental of neuroscience is to connect the firing of neurons to
physiological and behavioral outcomes. Chemogenetics enables researchers to
control the activity of a genetically defined population of neurons in vivo
through the expression of designer receptor exclusively activated by designer
drug (DREADD) in specific neurons and the administration of its synthetic ligand
clozapine N-oxide (CNO) (Sternson and Roth, 2014). Using stimulatory Gq-coupled
DREADD (hM3Dq) in mice, we showed that leptin receptor (LepRb)-expressing neurons
in the preoptic area (POA) of the hypothalamus are warm-sensitive neurons that
mediate warm-responsive metabolic and behavioral adaptations by reducing energy
expenditure and food intake (Yu et al., 2016). We also used DREADD technology to
test effects of chronic stimulation of POA LepRb neurons on energy expenditure,
food intake, and body weight with the TSE indirect calorimetry system. Here we
describe the detailed protocol of how we used indirect calorimetry to study the
outcome of chronic stimulation of POA LepRb neurons. This protocol can be adapted
to study long-term metabolic and behavioral consequences of other neuronal
modulations, with possible modifications to the type of DREADD, duration of CNO
treatment, or method of CNO delivery.
PMID- 29951572
TI - Nab Escaping AAV Mutants Isolated from Mouse Muscles.
AB - Neutralizing antibodies (Nabs) are a major challenge in clinical trials of adeno
associated virus (AAV) vector gene therapy, because Nabs are able to inhibit AAV
transduction in patients. We have successfully isolated several novel Nab-escaped
AAV chimeric capsids in mice by administrating a mixture of AAV shuffled library
and patient serum. These AAV chimeric capsid mutants enhanced Nab evasion from
patient serum with a high muscle transduction efficacy. In this protocol, we
describe the procedures for selection of the Nab-escaped AAV chimeric capsid,
including isolation and characterization of Nab-escaping AAV mutants in mice
muscle.
PMID- 29951571
TI - Purification of Total RNA from DSS-treated Murine Tissue via Lithium Chloride
Precipitation.
AB - We have developed a protocol to purify RNA from DSS (Dextran Sulfate Sodium)
treated mouse tissues. This method, which prevents downstream inhibition of q-RT
PCR observed in DSS-treated tissues, relies on successive precipitations with
lithium chloride.
PMID- 29951574
TI - Clinical Trials Corner.
PMID- 29951573
TI - Delay in the Provision of Antiretroviral Therapy to HIV-infected TB Patients in
Nigeria.
AB - Background: Nigeria has a high burden of HIV and tuberculosis (TB). To reduce TB
associated morbidity and mortality, the World Health Organization recommends that
HIV-positive TB patients receive antiretroviral therapy (ART) within eight weeks
of TB treatment initiation, or within two weeks if profoundly immunosuppressed
(CD4<50 cell/MUL). Methods: TB and HIV clinical records from facilities in two
Nigerian states between October 1st, 2012 and September 30th, 2013 were
retrospectively reviewed to assess uptake and timing of ART initiation among HIV
positive TB patients. Healthcare workers were qualitatively interviewed to assess
TB/HIV knowledge and barriers to timely ART. Results: Data were abstracted from
4,810 TB patient records, of which 1,249 (26.0%) had HIV-positive or unknown HIV
status documented, and the 574 (45.9%) HIV-positive TB patients were evaluated
for timing of ART uptake relative to TB treatment. Among 484 (84.3%) HIV-positive
TB patients not already on ART, 256 (52.9%, 95% CI: 45.0-60.8) were not initiated
on ART during six months of TB treatment. 30.0% of 273 patients with a known
CD4>=50cells/MUL started ART within eight weeks, and 14.8% of 54 patients with a
known CD4<50cells/MUL started within the recommended two weeks. Only 42% of
health workers interviewed reported knowing to interpret guidelines on when to
initiate ART in HIV-positive TB patients based on CD4 cell count results. CD4
cell count significantly predicted timely ART uptake. Conclusion: A large
proportion of HIV-positive TB patients were not initiated on ART early or even at
all during TB treatment. Retraining of staff, and interventions to strengthen
referral systems should be implemented to ensure timely provision of ART among
HIV-positive TB patients in Nigeria.
PMID- 29951575
TI - Computational Systems Biology Approach for the Study of Rheumatoid Arthritis:
From a Molecular Map to a Dynamical Model.
AB - In this work we present a systematic effort to summarize current biological
pathway knowledge concerning Rheumatoid Arthritis (RA). We are constructing a
detailed molecular map based on exhaustive literature scanning, strict curation
criteria, re-evaluation of previously published attempts and most importantly
experts' advice. The RA map will be web-published in the coming months in the
form of an interactive map, using the MINERVA platform, allowing for easy access,
navigation and search of all molecular pathways implicated in RA, serving thus,
as an on line knowledgebase for the disease. Moreover the map could be used as a
template for Omics data visualization offering a first insight about the pathways
affected in different experimental datasets. The second goal of the project is a
dynamical study focused on synovial fibroblasts' behavior under different initial
conditions specific to RA, as recent studies have shown that synovial fibroblasts
play a crucial role in driving the persistent, destructive characteristics of the
disease. Leaning on the RA knowledgebase and using the web platform Cell
Collective, we are currently building a Boolean large scale dynamical model for
the study of RA fibroblasts' activation.
PMID- 29951576
TI - The impact of video speed on the decision-making process of sports officials.
AB - There is an increasing trend in association football (soccer) to assist referees
in their decision-making with video technology. For decisions such as whether a
goal has been scored or which player actually committed a foul, video technology
can provide more objective information and be valuable to increase decisional
accuracy. It is unclear, however, to what extent video replays can aid referee
decisions in the case of foul-play situations in which the decision is typically
more ambiguous. In this study, we specifically evaluated the impact of slow
motion replays on decision-making by referees. To this end, elite referees of
five different countries (n = 88) evaluated 60 different foul-play situations
taken from international matches, replayed in either real time or slow motion.
Our results revealed that referees penalized situations more severely in slow
motion compared to real time (e.g. red card with a yellow card reference
decision). Our results provide initial evidence that video replay speed can have
an important impact on the disciplinary decision given by the referee in case of
foul play. The study also provides a real-life test-case for theories and
insights regarding causality perception.
PMID- 29951577
TI - Development of Parvalbumin-Expressing Basket Terminals in Layer II of the Rat
Medial Entorhinal Cortex.
AB - Grid cells in layer II of the medial entorhinal cortex (MEC LII) generate
multiple regular firing fields in response to the position and speed of an
individual within the environment. They exhibit a protracted postnatal
development and, in the adult, show activity differences along the dorsoventral
axis (DVA). Evidence suggests parvalbumin-positive (PV+) interneurons, most of
which are perisomatic-targeting cells, play a crucial role in generation of the
hexagonal grid cell activity pattern. We therefore hypothesized that the
development and organization of PV+ perisomatic terminals in MEC LII reflect the
postnatal emergence of the hexagonal firing pattern and dorsoventral differences
seen in grid cell activity. We used immuno-electron microscopy to examine the
development of PV+ perisomatic terminals and their target somata within dorsal
and ventral MEC LII in rats of postnatal day (P)10, P15, and P30. We demonstrate
that in dorsal and ventral MEC LII, the cross-sectional area of somata and number
and density of perisomatic PV+ terminals increase between P10 and P15. A
simultaneous decrease was observed in cross-sectional area of PV+ terminals.
Between P15 and P30, both MEC regions showed an increase in PV+ terminal size and
percentage of PV+ terminals containing mitochondria, which may enable grid cell
activity to emerge and stabilize. We also report that dorsal somata are larger
and apposed by more PV+ terminals than ventral somata at all stages, suggesting a
protracted maturation in the ventral portion and a possible gradient in soma size
and PV+ basket innervation along the DVA in the adult.
PMID- 29951578
TI - Neurodynamic Evidence Supports a Forced-Excursion Model of Decision-Making under
Speed/Accuracy Instructions.
AB - Evolutionary pressures suggest that choices should be optimized to maximize
rewards, by appropriately trading speed for accuracy. This speed-accuracy
tradeoff (SAT) is commonly explained by variation in just the baseline-to
boundary distance, i.e., the excursion, of accumulation-to-bound models of
perceptual decision-making. However, neural evidence is not consistent with this
explanation. A compelling account of speeded choice should explain both overt
behavior and the full range of associated brain signatures. Here, we reconcile
seemingly contradictory behavioral and neural findings. In two variants of the
same experiment, we triangulated upon the neural underpinnings of the SAT in the
human brain using both EEG and transcranial magnetic stimulation (TMS). We found
that distinct neural signals, namely the event-related potential (ERP)
centroparietal positivity (CPP) and a smoothed motor-evoked potential (MEP)
signal, which have both previously been shown to relate to decision-related
accumulation, revealed qualitatively similar average neurodynamic profiles with
only subtle differences between SAT conditions. These signals were then modelled
from behavior by either incorporating traditional boundary variation or utilizing
a forced excursion. These model variants are mathematically equivalent, in terms
of their behavioral predictions, hence providing identical fits to correct and
erroneous reaction time distributions. However, the forced-excursion version
instantiates SAT via a more global change in parameters and implied neural
activity, a process conceptually akin to, but mathematically distinct from,
urgency. This variant better captured both ERP and MEP neural profiles,
suggesting that the SAT may be implemented via neural gain modulation, and
reconciling standard modelling approaches with human neural data.
PMID- 29951579
TI - Foreground-Background Segmentation Revealed during Natural Image Viewing.
AB - One of the major challenges in visual neuroscience is represented by foreground
background segmentation. Data from nonhuman primates show that segmentation leads
to two distinct, but associated processes: the enhancement of neural activity
during figure processing (i.e., foreground enhancement) and the suppression of
background-related activity (i.e., background suppression). To study foreground
background segmentation in ecological conditions, we introduce a novel method
based on parametric modulation of low-level image properties followed by
application of simple computational image-processing models. By correlating the
outcome of this procedure with human fMRI activity, measured during passive
viewing of 334 natural images, we produced easily interpretable "correlation
images" from visual populations. Results show evidence of foreground enhancement
in all tested regions, from V1 to lateral occipital complex (LOC), while
background suppression occurs in V4 and LOC only. Correlation images derived from
V4 and LOC revealed a preserved spatial resolution of foreground textures,
indicating a richer representation of the salient part of natural images, rather
than a simplistic model of object shape. Our results indicate that scene
segmentation occurs during natural viewing, even when individuals are not
required to perform any particular task.
PMID- 29951581
TI - TP53 protein levels, RNA-based pathway assessment, and race among invasive breast
cancer cases.
AB - Mutations in tumor suppressor TP53 have been inconsistently linked to breast
cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary
clinical means of TP53 mutation determination, only detects mutations that
facilitate protein accumulation (e.g., missense mutations). RNA-based pathway
methods capture functional status and may aid in understanding the role of TP53
function in racial disparities of breast cancer. TP53 status was assessed among
invasive breast cancer cases from the Carolina Breast Cancer Study (CBCS) (2008
2013) using IHC and an established RNA-based TP53 signature (CBCS and The Cancer
Genome Atlas (TCGA)). Frequency of TP53 status (IHC, RNA-based) was estimated in
association with tumor characteristics, PAM50 intrinsic subtype, age, and race
using relative frequency differences (RFDs) and 95% confidence intervals (95% CI)
as the measure of association. Approximately 60% of basal-like tumors were TP53
protein positive (IHC), while nearly 100% were TP53 mutant-like (RNA). Luminal A
tumors had low frequency of TP53 positivity (IHC: 7.9%) and mutant-like status
(RNA: 1.7%). Mutant-like TP53 (RNA) was strongly associated with age <=50 years,
high tumor grade, advanced stage of disease, large tumor size, and basal-like and
HER2 intrinsic subtypes. Black race was strongly associated with TP53 mutant-like
status (RNA) (RFD: 24.8%, 95% CI: 20.5, 29.0) even after adjusting for age,
grade, stage (RFD: 11.3%; 95% CI: 7.6, 15.0). Associations were attenuated and
non-significant when measured by IHC. IHC-based TP53 status is an insensitive
measurement of TP53 functional status. RNA-based methods suggest a role for TP53
in tumor prognostic features and racial disparities.
PMID- 29951582
TI - Cdk4/6 inhibitors and overall survival: power of first-line trials in metastatic
breast cancer.
AB - Palbociclib, ribociclib, and abemaciclib have been investigated in combination
with aromatase inhibitors as first-line therapy for metastatic hormone receptor
positive breast cancer (PALOMA-2, MONALEESA-2 and MONALEESA-7, MONARCH-3 trials,
respectively); pivotal trials led to absolute median progression-free survival
(PFS) gain of about 15 months. We aimed to estimate, for each trial, the
statistical power to demonstrate a significant gain in overall survival (OS).
Power was calculated with Freedman's formula. Given the allocation ratio and the
number of events, power was computed as a function of hazard ratio. We focused on
four specific hazard ratio values (0.94, 0.89, 0.81, and 0.77), which are
estimated to correspond to absolute 3, 6, 12, and 15 months gain in OS,
respectively. For these calculations, the type I error rate was stated at 5% with
a two-sided test, and we assumed that the risk of death was constant over time.
PALOMA-2 and MONALEESA trials have an almost similar power despite different
allocation ratios, while MONARCH-3 has a more limited power. Overall, the power
of the four trials to demonstrate a statistically significant improvement in OS
is less than 70% if the prolongation in median OS is <=12 months, whatever the OS
data maturity. This analysis shows that OS results are jeopardized by limited
powers, and a meta-analysis might be required to demonstrate OS benefit.
Conversely, if a significant OS improvement is observed in some but not at all
trials, this discrepancy might be more attributable to chance than to a truly
different drug efficacy.
PMID- 29951580
TI - Cognitive impairment in Parkinson's disease: a report from a multidisciplinary
symposium on unmet needs and future directions to maintain cognitive health.
AB - People with Parkinson's disease (PD) and their care partners frequently report
cognitive decline as one of their greatest concerns. Mild cognitive impairment
affects approximately 20-50% of people with PD, and longitudinal studies reveal
dementia in up to 80% of PD. Through the Parkinson's Disease Foundation Community
Choice Research Award Program, the PD community identified maintaining cognitive
function as one of their major unmet needs. In response, a working group of
experts across multiple disciplines was organized to evaluate the unmet needs,
current challenges, and future opportunities related to cognitive impairment in
PD. Specific conference goals included defining the current state in the field
and gaps regarding cognitive issues in PD from patient, care partner, and
healthcare professional viewpoints; discussing non-pharmacological interventions
to help maintain cognitive function; forming recommendations for what people with
PD can do at all disease stages to maintain cognitive health; and proposing ideas
for how healthcare professionals can approach cognitive changes in PD. This paper
summarizes the discussions of the conference, first by addressing what is
currently known about cognitive dysfunction in PD and discussing several non
pharmacological interventions that are often suggested to people with PD. Second,
based on the conference discussions, we provide considerations for people with PD
for maintaining cognitive health and for healthcare professionals and care
partners when working with people with PD experiencing cognitive impairment.
Furthermore, we highlight key issues and knowledge gaps that need to be addressed
in order to advance research in cognition in PD and improve clinical care.
PMID- 29951583
TI - Oxygen-deficient triple perovskites as highly active and durable bifunctional
electrocatalysts for oxygen electrode reactions.
AB - Highly active and durable bifunctional oxygen electrocatalysts have been of
pivotal importance for renewable energy conversion and storage devices, such as
unitized regenerative fuel cells and metal-air batteries. Perovskite-based oxygen
electrocatalysts have emerged as promising nonprecious metal bifunctional
electrocatalysts, yet their catalytic activity and stability still remain to be
improved. We report a high-performance oxygen electrocatalyst based on a triple
perovskite, Nd1.5Ba1.5CoFeMnO9-delta (NBCFM), which shows superior activity and
durability for oxygen electrode reactions to single and double perovskites. When
hybridized with nitrogen-doped reduced graphene oxide (N-rGO), the resulting
NBCFM/N-rGO catalyst shows further boosted bifunctional oxygen electrode activity
(0.698 V), which surpasses that of Pt/C (0.801 V) and Ir/C (0.769 V) catalysts
and which, among the perovskite-based electrocatalysts, is the best activity
reported to date. The superior catalytic performances of NBCFM could be
correlated to its oxygen defect-rich structure, lower charge transfer resistance,
and smaller hybridization strength between O 2p and Co 3d orbitals.
PMID- 29951584
TI - Nanoscale momentum-resolved vibrational spectroscopy.
AB - Vibrational modes affect fundamental physical properties such as the conduction
of sound and heat and can be sensitive to nano- and atomic-scale structure.
Probing the momentum transfer dependence of vibrational modes provides a wealth
of information about a materials system; however, experimental work has been
limited to essentially bulk and averaged surface approaches or to small wave
vectors. We demonstrate a combined experimental and theoretical methodology for
nanoscale mapping of optical and acoustic phonons across the first Brillouin
zone, in the electron microscope, probing a volume ~1010 to 1020 times smaller
than that of comparable bulk and surface techniques. In combination with more
conventional electron microscopy techniques, the presented methodology should
allow for direct correlation of nanoscale vibrational mode dispersions with
atomic-scale structure and chemistry.
PMID- 29951587
TI - Real Vegan Cheese and the Artistic Critique of Biotechnology.
AB - Drawing on the case study of Real Vegan Cheese (RVC), a synthetic biology project
housed in a community lab or "biohackerspace," I argue that biohacking performs
an "artistic critique" of the bioeconomy. Following Boltanski and Chiapello's use
of the term, the "artistic critique" pits values of autonomy and creativity
against a view of capitalist production as standardized and alienating,
represented (in the case of biotechnology) by Monsanto's monoculture GMOs. In
this way, biohacking is depicted as liberating biotechnology from the constraints
of corporate and academic institutions. Through the use of design fiction and a
playful aesthetic, projects such as RVC demonstrate a more legitimate--with
respect to the values of the artistic critique--mode of production for a new
generation of biotechnology products, one that is portrayed as driven primarily
by ethical and aesthetic values rather than the profit motive. This analysis
highlights the role that aesthetic and affective strategies play in advancing
particular sociotechnical visions, and the way that biohacking projects operate
in symbiosis with incumbent institutions even as they define themselves in
opposition to them. Finally, it suggests that biohacking has certain limitations
when considered as a form of public engagement with science.
PMID- 29951585
TI - G protein-coupled receptors: the evolution of structural insight.
AB - G protein-coupled receptors (GPCR) comprise a diverse superfamily of over 800
proteins that have gained relevance as biological targets for pharmaceutical drug
design. Although these receptors have been investigated for decades, three
dimensional structures of GPCR have only recently become available. In this
review, we focus on the technological advancements that have facilitated efforts
to gain insights into GPCR structure. Progress in these efforts began with the
initial crystal structure determination of rhodopsin (PDB: 1F88) in 2000 and has
continued to the most recently published structure of the A1AR (PDB: 5UEN) in
2017. Numerous experimental developments over the past two decades have opened
the door for widespread GPCR structural characterization. These efforts have
resulted in the determination of three-dimensional structures for over 40
individual GPCR family members. Herein we present a comprehensive list and
comparative analysis of over 180 individual GPCR structures. This includes a
summary of different GPCR functional states crystallized with agonists, dual
agonists, partial agonists, inverse agonists, antagonists, and allosteric
modulators.
PMID- 29951586
TI - Neonatal Intermittent Hypoxia, Reactive Oxygen Species, and Oxygen-Induced
Retinopathy.
AB - Most of the major morbidities in the preterm newborn are caused by or are
associated with oxygen-induced injuries and are aptly called "oxygen radical
diseases in neonatology or ORDIN". These include bronchopulmonary dysplasia,
retinopathy of prematurity, periventricular leukomalacia, intraventricular
hemorrhage, necrotizing enterocolitis and others. Relative hyperoxia immediately
after birth, immature antioxidant systems, biomolecular events favoring oxidative
stress such as iron availability and the role of hydrogen peroxide as a key
molecular mediator of these events are reviewed. Potential therapeutic strategies
such as caffeine, antioxidants, non-steroidal anti-inflammatory drugs, and others
targeted to these critical sites may help prevent oxidative radical diseases in
the newborn resulting in improved neonatal outcomes.
PMID- 29951589
TI - Future directions of resveratrol research.
AB - Resveratrol improves healthspan and lifespan in many organisms. Several different
targets and mechanisms of action have been proposed to explain the beneficial
effects of resveratrol on healthspan and longevity, including the activation of a
family of proteins known as sirtuins and its action as a calorie restriction
mimetic. In this mini-review, we discuss some of the most recent findings to date
in the resveratrol field and suggest three areas of future research based on
those results.
PMID- 29951590
TI - Skin aging as a mechanical phenomenon: The main weak links.
AB - From a mechanical point of view, human skin appears as a layered composite
containing the stiff thin cover layer presented by the stratum corneum, below
which are the more compliant layers of viable epidermis and dermis and further
below the much more compliant adjacent layer of subcutaneous white adipose tissue
(sWAT). Upon exposure to a strain, such a multi-layer system demonstrates
structural instabilities in its stiffer layers, which in its simplest form is the
wrinkling. These instabilities appear hierarchically when the mechanical strain
in the skin exceeds some critical values. Their appearance is mainly dependent on
the mismatch in mechanical properties between adjacent skin layers or between the
skin and sWAT, on the adhesive strength and thickness ratios between the layers,
on their bending and tensile stiffness as well as on the value of the stress
existing in single layers. Gradual reduction of elastic fibers in aging
significantly reduces the skin's ability to bend, prompting an up to 4-fold
reduction of its stability against wrinkling, thereby explaining the role of
these fibers in skin aging. While chronological and extrinsic aging differently
modify these parameters, they lead to the same end result, reducing the critical
strain required for the onset of instabilities. Comparing of mechanical
properties of the skin presented as a bi-, tri- or tetra-layer structure
demonstrates the particular importance of the papillary dermis in skin aging and
provides the arguments to consider the undulations on the dermal-epidermal and
dermal-sWAT interfaces as the result of mechanical bifurcation, leading to
structural instabilities inside of the skin. According to this model, anti-aging
strategies should focus not as much on the reinforcement of the dermis, but
rather aim to treat the elastic mismatch between different adjacent layers in the
skin and sWAT as well as the adhesion between these layers.
PMID- 29951588
TI - Gut microbiome and aging: Physiological and mechanistic insights.
AB - The development of human gut microbiota begins as soon as the neonate leaves the
protective environment of the uterus (or maybe in-utero) and is exposed to
innumerable microorganisms from the mother as well as the surrounding
environment. Concurrently, the host responses to these microbes during early life
manifest during the development of an otherwise hitherto immature immune system.
The human gut microbiome, which comprises an extremely diverse and complex
community of microorganisms inhabiting the intestinal tract, keeps on fluctuating
during different stages of life. While these deviations are largely natural,
inevitable and benign, recent studies show that unsolicited perturbations in gut
microbiota configuration could have strong impact on several features of host
health and disease. Our microbiota undergoes the most prominent deviations during
infancy and old age and, interestingly, our immune health is also in its weakest
and most unstable state during these two critical stages of life, indicating that
our microbiota and health develop and age hand-in-hand. However, the mechanisms
underlying these interactions are only now beginning to be revealed. The present
review summarizes the evidences related to the age-associated changes in
intestinal microbiota and vice-versa, mechanisms involved in this bi-directional
relationship, and the prospective for development of microbiota-based
interventions such as probiotics for healthy aging.
PMID- 29951591
TI - Practice effects in nutrition intervention studies with repeated cognitive
testing.
AB - BACKGROUND: There is growing interest in the use of nutrition interventions to
improve cognitive function. To determine intervention efficacy, repeated
cognitive testing is often required. However, performance on tasks can improve
through practice, irrespective of any intervention. OBJECTIVE: This study
investigated practice effects for commonly used cognitive tasks (immediate and
delayed recall, serial subtractions, Stroop and the Sternberg task) to identify
appropriate methodology for minimising their impact on nutrition intervention
outcomes. METHODS: Twenty-nine healthy young adults completed six repetitions of
the cognitive battery (two sessions on each of three separate visits). Subjective
measures of mood, motivation and task difficulty were also recorded at each
repetition. RESULTS: Significant practice effects were apparent for all tasks
investigated and were attenuated, but not fully eliminated, at later visits
compared with the earlier visits. Motivation predicted cognitive performance for
the tasks rated most difficult by participants (serial 7s, immediate and delayed
recall). While increases in mental fatigue and corresponding decreases in
positive mood were observed between test sessions occurring on the same day,
there were no negative consequences of long term testing on mood across the
duration of the study. CONCLUSION: Practice effects were evident for all
investigated cognitive tasks, with strongest effects apparent between visits one
and two. Methodological recommendations to reduce the impact of practice on the
statistical power of future intervention studies have been made, including the
use of alternate task forms at each repetition and the provision of a
familiarisation visit on a separate day prior to data collection.
PMID- 29951592
TI - Curcumin supplementation and motor-cognitive function in healthy middle-aged and
older adults.
AB - BACKGROUND: Recent studies suggest curcumin is a promising nutraceutical for
improving important clinical and physiological markers of healthy aging,
including motor and cognitive function. OBJECTIVE: To determine if curcumin
supplementation improves motor and cognitive function in healthy middle-aged and
older adults. METHODS: 39 healthy men and postmenopausal women (45-74 yrs) were
randomized to 12 weeks of placebo (n = 19) or curcumin supplementation (2000
mg/day Longvida(r); n = 20) with motor and cognitive function assessed at week 0
and 12. RESULTS: Using measures of the NIH Toolbox and other standardized tests,
there were no changes in muscle strength and rate of torque development,
dexterity, fatigability, mobility, endurance, and balance between the placebo and
curcumin groups after 12 weeks (all P > 0.05). Additionally, there were no
changes after 12 weeks of placebo and curcumin supplementation in measures of
fluid cognitive ability, a cognitive domain that declines with age, including
processing speed, executive function, working memory, and episodic memory (all P
> 0.3). There were marginal changes in language, a measure of crystallized
cognitive ability that is stable with age, following the intervention, wherein
reading decoding increased 3% in the curcumin group (post: 2428+/-35 vs. pre:
2357+/-34, P = 0.003), but was unchanged in the placebo group (post: 2334+/-39
vs. pre: 2364+/-40, P = 0.07). CONCLUSIONS: Overall, 12 weeks of curcumin
supplementation does not improve motor and cognitive functions in healthy middle
aged and older adults. It is possible that curcumin may enhance these functions
in groups with greater baseline impairments than those studied here, including
adults greater than 75 years of age and/or patients with clinical disorders.
PMID- 29951593
TI - Relationships between the inflammatory potential of the diet, aging and
anthropometric measurements in a cross-sectional study in Pakistan.
AB - BACKGROUND: Little is known about associations between dietary inflammation, age
and anthropometric measurements. OBJECTIVE: In this regard, we examine how DII is
related to age, anthropometrics [weight, Body mass index (BMI), waist to hip
ratio (WHR)] and other parameters of nutrition (energy, protein, fats and
cholesterol intake, Net Endogenous Acid Production (NEAP) and Phytochemical Index
(PI)) in a cross-sectional study in Pakistan. DESIGN: Only men (n = 651, age 54
95 years) participated in the study. Anthropometric data were collected using
standard methods. DII was calculated from nutrients derived from 24-hr Dietary
Recall questionnaires. NEAP and PI were calculated by established algorithms
using information on nutrient intake. RESULTS: The results show that with
increasing age, there was a significant increase in the DII score (p < 0.05).
Similarly significant positive correlations were found between DII score and
weight, BMI, WHR and % BF (p, for all trends < 0.05). DII score significantly
positively correlated with the dietary factors studied i.e. energy, protein, and
fats (p, for all trends < 0.0001) but non-significantly with cholesterol (p >
0.05). Similarly, a significant positive correlation with NEAP (p < 0.0001) was
found, but negative with PI (p < 0.0001). CONCLUSION: In conclusion, the present
study shows direct positive correlations between the DII, age and indices of
obesity, and thus supports the hypothesis that diet may have a role in the
development of obesity through inflammatory modulation mechanisms in elderly.
PMID- 29951594
TI - Effects of 8-hour time restricted feeding on body weight and metabolic disease
risk factors in obese adults: A pilot study.
AB - BACKGROUND: Time restricted feeding decreases energy intake without calorie
counting and may be a viable option for weight loss. However, the effect of this
diet on body weight in obese subjects has never been examined. OBJECTIVE: This
study investigated the effects of 8-h time restricted feeding on body weight and
metabolic disease risk factors in obese adults. DESIGN: Obese subjects (n = 23)
participated in an 8-h time restricted feeding intervention (ad libitum feeding
between 10:00 to 18:00 h, water fasting between 18:00 to 10:00 h) for 12 weeks.
Weight loss and other outcomes were compared to a matched historical control
group (n = 23). RESULTS: Body weight and energy intake decreased in the time
restricted group (-2.6% +/- 0.5; -341 +/- 53 kcal/d) relative to controls over 12
weeks (P < 0.05). Systolic blood pressure decreased in the time restricted
feeding group (-7 +/- 2 mm Hg) versus controls (P < 0.05). Fat mass, lean mass,
visceral fat mass, diastolic blood pressure, LDL cholesterol, HDL cholesterol,
triglycerides, fasting glucose, fasting insulin, HOMA-IR, and homocysteine were
not significantly different from controls after 12 weeks (no group*time
interaction). CONCLUSION: These findings suggest that 8-h time restricted feeding
produces mild caloric restriction and weight loss, without calorie counting. It
may also offer clinical benefits by reducing blood pressure.
PMID- 29951595
TI - Clinical Trials Corner.
PMID- 29951596
TI - Vitamin D Supplementation, Glycemic Control, and Insulin Resistance in
Prediabetics: A Meta-Analysis.
AB - Diabetes prevention is a public health priority. Vitamin D supplementation may
help prevent the development of diabetes in persons at increased risk. We
performed a meta-analysis of controlled clinical trials that assessed glycemic
outcome measures among adults at risk for type 2 diabetes, including prediabetes,
overweight, or obesity. We searched PUBMED/ MEDLINE, CINAHL, and Google Scholar
databases for trials published prior to April 2017. Placebo-controlled clinical
trials with random allocation to vitamin D with or without calcium
supplementation were selected. Data collection included country, study design,
inclusion criteria, sample size, form, and dose of vitamin D, supplementation
interval, control group, duration, participant characteristics, comorbidities,
baseline and follow-up serum 25-hydroxyvitamin D [25(OH)D] concentration, and
available outcome measures [glycosylated hemoglobin (HbA1c), fasting plasma
glucose, plasma glucose after 2-hour oral glucose tolerance test, and homeostatic
model assessment of insulin resistance (HOMA-IR)]. Data synthesis was conducted
using random-effect models (PROSPERO registration no. CRD42017055326). Twenty
eight trials, representing 3848 participants, met the eligibility criteria.
Compared with the control group, vitamin D supplementation significantly reduced
HbA1c level by -0.48% (95% CI, -0.79 to -0.18), fasting plasma glucose level by
0.46 mmol/L (95% CI, -0.74 to -0.19), and HOMA-IR level by -0.39 (95% CI, -0.68
to -0.11). Subgroup analysis revealed that the effects of vitamin D
supplementation on different glycemic measures were influenced by age, calcium
coadministration, vitamin D deficiency, serum 25(OH)D level after
supplementation, and duration of supplementation. Vitamin D supplementation and
improved vitamin D status improved glycemic measures and insulin sensitivity and
may be useful as part of a preventive strategy for type 2 diabetes.
PMID- 29951598
TI - BJS Open.
PMID- 29951597
TI - Identifying a Clinically Applicable Mutational Burden Threshold as a Potential
Biomarker of Response to Immune Checkpoint Therapy in Solid Tumors.
AB - Purpose: An association between mutational burden and response to immune
checkpoint therapy has been documented in several cancer types. The potential for
such a mutational burden threshold to predict response to immune checkpoint
therapy was evaluated in several clinical datasets, where mutational burden was
measured either by whole-exome sequencing (WXS) or using commercially available
sequencing panels. Methods: WXS and RNA-seq data of 33 solid cancer types from
TCGA were analyzed to determine whether a robust immune checkpoint activating
mutation (iCAM) burden threshold associated with evidence of immune checkpoint
activation exists in these cancers that may serve as a biomarker for response to
immune checkpoint blockade therapy. Results: We find that a robust iCAM
threshold, associated with signatures of immune checkpoint activation, exists in
8 of 33 solid cancers: melanoma, lung adenocarcinoma, colon adenocarcinoma,
endometrial cancer, stomach adenocarcinoma, cervical cancer, ER+HER2- breast
cancer, and bladder-urothelial cancer. Tumors with mutational burden higher than
the threshold (iCAM+) also had clear histologic evidence of lymphocytic
infiltration. In published datasets of melanoma, lung adenocarcinoma and colon
cancer, patients with iCAM+ tumors had significantly better response to immune
checkpoint therapy compared to those with iCAM- tumors. ROC analysis using TCGA
predictions as gold standard showed that iCAM+ tumors are accurately identifiable
using clinical sequencing assays, such as FoundationOne or StrandAdvantage. Using
the FoundationOne derived threshold, analysis of 113 melanoma tumors, showed that
iCAM+ patients have significantly better response to immune checkpoint therapy.
iCAM+ and iCAM- tumors have distinct mutation patterns and different immune
microenvironments. Conclusion: In 8 solid cancers, a mutational burden threshold
exists that may predict response to immune checkpoint blockade. This threshold is
identifiable using available clinical sequencing assays.
PMID- 29951600
TI - Surgery for massive splenomegaly.
AB - Background: Splenectomy for massive splenomegaly (spleen weight more than 1.5 kg)
is commonly believed to be hazardous and to provide poor palliation. The aim of
this cohort study was to investigate these issues and examine the many
definitions of massive splenomegaly to see whether a better tool might be
proposed for preoperative evaluation of these patients. Methods: Morbidity and
long-term outcomes were assessed in consecutive patients. Relief of pressure
volume-related symptoms and sustainable independence from transfusion in patients
were used to ascertain the impact of splenectomy. Results: Splenectomy was
performed in 56 patients, mainly for non-Hodgkin's lymphoma and
myeloproliferative diseases. Median spleen weight was 2.3 (range 1.5-6.0) kg.
Mortality at 180 days was zero, and the postoperative complication rate was 25
per cent (17 complications in 14 patients). At 2 years, relief of pain was
maintained in 33 of 34 patients, with sustained independence from transfusion in
15 of 19 patients with anaemia and nine of 11 with thrombocytopenia. Spleen
weight correlated negatively with BMI (P = 0.036). Conclusion: Splenectomy for
massive splenomegaly is safe and provides effective palliation. Provisional cut
off points relating to spleen size and BMI help to identify patients benefiting
from a splenectomy, even those in a critical state.
PMID- 29951599
TI - Randomized clinical trial of ultrasonic scissors versus conventional haemostasis
to compare complications and economics after total thyroidectomy (FOThyr).
AB - Background: The benefits of single-use ultrasonic scissors in thyroid surgery are
still debated. Although this device has been shown to reduce operating time
compared with conventional haemostasis, its cost-effectiveness has never been
demonstrated. The aim of this study was to evaluate the efficacy, cost
effectiveness and safety of ultrasonic scissors for total thyroidectomy. Methods:
This was a prospective, randomized, multicentre trial conducted at 13 hospital
sites. The primary endpoint was the percentage of patients with hypocalcaemia
(serum calcium level below 2 mmol/l) on day 2. Secondary endpoints included
postoperative complications and costs, with calculation of incremental cost
differences and cost-effectiveness ratios. Results: In total, 1329 patients who
underwent total thyroidectomy were included in the analysis: 670 were randomized
to treatment with ultrasonic scissors and 659 to conventional haemostasis. There
was no difference between groups in the rate of complications, including
hypocalcaemia on day 2 (19.7 per cent in ultrasonic scissors group versus 20.3
per cent in conventional haemostasis group; P = 0.743). Median operating times
were significantly shorter with ultrasonic scissors (90 versus 100 min with
conventional haemostasis; P < 0.001). Total mean(s.d.) direct costs at 6 months
were ?4311(1547) and ?4011(1596) respectively (P < 0.001). Conclusion: Ultrasonic
scissors were no more clinically effective than conventional haemostasis, but use
of these devices was more costly. Registration number: NCT01551914
(http://www.clinicaltrials.gov).
PMID- 29951601
TI - Development of incisional herniation after midline laparotomy.
AB - Background: Incisional herniation is a common complication after abdominal
surgery associated with considerable morbidity. The aim of this study was to
determine whether incisional hernia is an early complication, in order to
understand better the aetiology of incisional hernia formation. Methods: This
study involved the secondary analysis of a subset of patients included in a large
RCT comparing small and large tissue bites (5 mm every 5 mm, or 1 cm every 1 cm)
in patients scheduled to undergo elective abdominal surgery by midline
laparotomy. The distance between the rectus abdominis muscles (RAM distance) was
measured by standardized ultrasound imaging 1 month and 1 year after surgery. The
relationship between the 1-year incidence of incisional hernia and the RAM
distance at 1 month was investigated. Results: Some 219 patients were
investigated, 113 in the small-bites and 106 in the large-bites group. At 1 month
after surgery the RAM distance was smaller for small bites than for large bites
(mean(s.d.) 1.90(1.18) versus 2.39(1.34) cm respectively; P = 0.005). At 1 year,
patients with incisional hernia had a longer RAM distance at 1 month than those
with no incisional hernia (mean(s.d.) 2.43(1.48) versus 2.03(1.19) cm
respectively; relative risk 1.14, 95 per cent c.i. 1.03 to 1.26, P = 0.015).
Conclusion: A RAM distance greater than 2 cm at 1 month after midline laparotomy
is associated with incisional hernia. Closure with small bites results in a
smaller distance between the muscles.
PMID- 29951602
TI - Natural orifice transluminal endoscopic surgery for colorectal cancer.
AB - Background: Natural orifice transluminal endoscopic surgery (NOTES) has
theoretical advantages over other approaches. Methods: This was a prospective
cohort study of colorectal cancers operated on by NOTES (transanally for rectal
tumours, transvaginally for sigmoid tumours) between December 2013 and December
2015, with a minimum follow-up of 1 year. Eligibility criteria included ASA
fitness grade I-III, BMI below 25 kg/m2 and TNM stage T3 N0 M0. Exclusion
criteria included pregnancy or distant metastasis. The anastomosis was either
handsewn or performed mechanically. Results: Sixteen patients were operated on by
a transanal and four by a transvaginal approach. There were ten men and ten
women, with a mean(s.d.) age of 55.6(12.1) years. Mean BMI was 22.4(2.6) kg/m2.
Four anterior, 11 low anterior and five intersphincteric resections were
performed for 16 rectal and four low sigmoid tumours. The mean duration of
surgery was 258(11) min. No conversion to laparotomy was needed, and there were
no deaths. Five patients required additional ports, for intraoperative bleeding
(1), suture of an intraoperative urethral injury with covering ileostomy (1) and
difficulty in dissection (3). One patient had an anastomotic leak requiring
transanal closure and ileostomy on day 7. Both ileostomies were closed after 2
months. The mean hospital stay was 6.4(1.8) days. All resections were R0.
Conclusion: In carefully selected patients NOTES for colorectal cancer resection
was feasible and effective.
PMID- 29951603
TI - Nationwide population-based cohort study to assess risk of surgery for adhesive
small bowel obstruction following open or laparoscopic rectal cancer resection.
AB - Background: Laparoscopic surgery has been reported to reduce the formation of
adhesions following colorectal surgery. The aim of this nationwide cohort study
was to investigate the risk of surgery for adhesive small bowel obstruction (SBO)
following open and laparoscopic rectal cancer resection. Methods: Patients
undergoing rectal cancer resection between 2005 and 2013 were identified in the
Danish Colorectal Cancer Group database. The primary outcome of surgery for
adhesive SBO was identified in the Danish National Patient Registry. The risk of
surgery for adhesive SBO was estimated as the cumulative incidence proportion,
treating death as a competing risk. Cox proportional hazards regression analysis
with multivariable adjustment was used to compute hazard ratios (HRs). The
secondary outcome was 30-day mortality after surgery for adhesive SBO. Results:
Of 7657 patients, 340 (4.4 per cent) underwent surgery for adhesive SBO. The 5
year risk of surgery for adhesive SBO was 4.5 per cent among 4472 patients
undergoing open resection and 3.0 per cent among 3185 patients having a
laparoscopic resection. Laparoscopic rectal resection was associated with a lower
risk of subsequent operation for adhesive SBO (adjusted HR 0.65, 95 per cent c.i.
0.50 to 0.86; P = 0.002). The adjusted HR of mortality after adhesive SBO was
0.84 (0.37 to 1.91; P = 0.671) comparing patients with previous laparoscopic and
open resection. Conclusion: Laparoscopic rectal cancer resection was associated
with a decreased risk of surgery for adhesive SBO. There was a substantial
difference in 30-day mortality after surgery for adhesive SBO based on the
surgical approach used at the time of rectal resection.
PMID- 29951604
TI - Impact of receptor phenotype on nodal burden in patients with breast cancer who
have undergone neoadjuvant chemotherapy.
AB - Background: Optimal evaluation and management of the axilla following neoadjuvant
chemotherapy (NAC) in patients with node-positive breast cancer remains
controversial. The aim of this study was to examine the impact of receptor
phenotype in patients with nodal metastases who undergo NAC to see whether this
approach can identify those who may be suitable for conservative axillary
management. Methods: Between 2009 and 2014, all patients with breast cancer and
biopsy-proven nodal disease who received NAC were identified from prospectively
developed databases. Details of patients who had axillary lymph node dissection
(ALND) following NAC were recorded and rates of pathological complete response
(pCR) were evaluated for receptor phenotype. Results: Some 284 patients with
primary breast cancer and nodal metastases underwent NAC and subsequent ALND,
including two with bilateral disease. The most common receptor phenotype was
luminal A (154 of 286 tumours, 53.8 per cent), with lesser proportions accounted
for by the luminal B-Her2 type (64, 22.4 per cent), Her2-overexpressing (38, 13.3
per cent) and basal-like, triple-negative (30, 10.5 per cent) subtypes. Overall
pCR rates in the breast and axilla were 19.9 per cent (54 of 271 tumours) and
37.4 per cent (105 of 281) respectively. Axillary pCR rates were highest in the
Her2-overexpressing group (27 of 35, 77 per cent) and lowest in the luminal A
group (35 of 153, 22.9 per cent) (P < 0.001). Nodal burden (median number of
positive nodes excised) was lower in the Her2-overexpressing group compared with
the luminal A group (0 versus 3; P < 0.001). Conclusion: Her2 positivity was
associated with increased rates of axillary pCR and reduced nodal burden
following NAC.
PMID- 29951605
TI - Familial clustering and risk of groin hernia in children.
AB - Background: The hypothesis was that groin hernias are hereditary. This study was
undertaken to establish the degree of familial clustering of groin hernias on a
nationwide scale. Methods: A register-based cohort was created consisting of all
children in Denmark whose parents were born in 1970 or later by the use of the
Danish Civil Registration System. Within this cohort, all groin hernia operations
were identified. To establish the risk estimates associated with a positive
family history of groin hernia operation, information on groin hernia operations
in fathers, mothers and siblings was also assessed. Results: In the cohort of 408
381 persons, a total of 4966 were operated on for groin hernia (incidence rate
2.12 per 1000 person-years at risk). A person with a mother who had undergone
surgery for a groin hernia had an increased risk of 2.89 (95 per cent c.i. 2.48
to 3.34) of having a groin hernia operation; a person with a father operated on
for a groin hernia had an increased risk of 1.75 (1.58 to 1.94); and a person
with a sibling operated on for a groin hernia had an increased risk of 2.54 (2.17
to 2.96). The strongest association was seen between mothers who had been
operated on for groin hernia and their daughters (increased risk 6.01, 95 per
cent c.i. 4.53 to 7.80), compared with the risk in girls who did not have a
mother who had undergone surgery for groin hernia. Conclusion: Groin hernias are
clustered in families, with the strongest relationship seen between mothers and
their daughters.
PMID- 29951606
TI - Association between hospital volume and in-hospital mortality following
radiofrequency ablation for hepatocellular carcinoma.
AB - Background: Radiofrequency ablation (RFA) is a minimally invasive treatment for
hepatocellular carcinoma (HCC). There is increasing evidence of an association
between increasing hospital volume and lower postoperative mortality for many
surgical procedures, but this is difficult to establish with minimally invasive
treatments, where postoperative mortality is low. The aim of this study was to
investigate the relationship between hospital volume and in-hospital mortality
following RFA using a Japanese nationwide database. Methods: Data from the
Diagnostic Procedure Combination database were analysed from 1 July 2010 to 31
March 2012. Multivariable logistic regression was used to analyse the
relationship between hospital volume and in-hospital mortality following RFA,
with adjustment for patient background. Results: Some 36 675 patients with HCC
were identified in the database. The overall in-hospital mortality rate from RFA
was 0.31 per cent. In-hospital mortality was significantly higher in low-volume
than high-volume hospitals (odds ratio 2.57, 95 per cent c.i. 1.61 to 4.09; P <
0.001). Higher in-hospital mortality was significantly associated with older age
and a higher Charlson Co-morbidity Index score. Conclusion: RFA for HCC was
associated with acceptably low mortality in Japan, but in-hospital mortality
following RFA was affected by hospital procedural volume.
PMID- 29951608
TI - Impact of performance in a mandatory postgraduate surgical examination on
selection into specialty training.
AB - Background: The Intercollegiate Membership of the Royal College of Surgeons
(MRCS) examination is undertaken by large numbers of trainees in the UK and
internationally as a mandatory step within surgical training. Unlike some high
stakes medical examinations, the MRCS is yet to be validated. A quantitative
study was undertaken to assess its predictive validity by investigating the
relationship between MRCS (Parts A and B) and national selection interview scores
for general and vascular surgery in the UK. Methods: Pearson correlation
coefficients were used to examine the linear relationship between each
assessment, and linear regression analyses were employed to identify potential
independent predictors of the national selection score. All UK medical graduates
who attempted the interview in 2011-2015 were included. Results: Some 84.4 per
cent of the candidates (1231 of 1458) were matched with MRCS data. There was a
significant positive correlation between the first attempt score at Part B of the
MRCS examination and the national selection score (r = 0.38, P < 0.001). In
multivariable analysis, 17 per cent of variance in the national selection first
attempt score was explained by the Part B MRCS score and number of attempts
(change in R 2 value of 0.10 and 0.07 respectively; P < 0.001). Candidates who
required more than two attempts at Part B were predicted to score 8.1 per cent
less than equally matched candidates who passed at their first attempt.
Conclusion: This study supports validity of the MRCS examination, and indicates
its predictive value regarding entry into specialist training.
PMID- 29951607
TI - Systematic review of surgical interventions for Crohn's anal fistula.
AB - Background: Anal fistula occurs in approximately one in three patients with
Crohn's disease and is typically managed through a multimodal approach. The
optimal surgical therapy is not yet clear. The aim of this systematic review was
to identify and assess the literature on surgical treatments of Crohn's anal
fistula. Methods: A systematic review was conducted that analysed studies
relating to surgical treatment of Crohn's anal fistula published on MEDLINE,
Embase and Cochrane databases between January 1995 and March 2016. Studies
reporting specific outcomes of patients treated for Crohn's anal fistula were
included. The primary outcome was fistula healing rate. Bias was assessed using
the Cochrane ROBINS-I and ROB tool as appropriate. Results: A total of 1628
citations were reviewed. Sixty-three studies comprising 1584 patients were
ultimately selected in the analyses. There was extensive reporting on the use of
setons, advancement flaps and fistula plugs. Randomized trials were available
only for stem cells and fistula plugs. There was inconsistency in outcome
measures across studies, and a high degree of bias was noted. Conclusion: Data
describing surgical intervention for Crohn's anal fistula are heterogeneous with
a high degree of bias. There is a clear need for standardization of outcomes and
description of study cohorts for better understanding of treatment options.
PMID- 29951609
TI - Risk factors for delayed gastric emptying following laparoscopic repair of very
large hiatus hernias.
AB - Background: Delayed gastric emptying can complicate surgery for hiatus hernia.
The aim of this study was to quantify its incidence following laparoscopic repair
of very large hiatus hernias, identify key risk factors for its occurrence and
determine its impact on clinical outcomes. Methods: Data collected from a
randomized trial of patients who underwent laparoscopic mesh versus sutured
repair of very large hiatus hernias (more than 50 per cent of stomach in chest)
were analysed retrospectively. Delayed gastric emptying was defined as endoscopic
evidence of solid food in the stomach after fasting for 6 h at 6 months after
surgery. Results: Delayed gastric emptying occurred in 19 of 102 patients (18.6
per cent). In univariable analysis, type 2 paraoesophageal hernia (relative risk
(RR) 3.15, 95 per cent c.i. 1.41 to 7.06), concurrent anterior and posterior
hiatal repair (RR 2.66, 1.14 to 6.18), hernia sac excision (RR 4.85, 1.65 to
14.24), 270 degrees /360 degrees fundoplication (RR 3.64, 1.72 to 7.68),
division of short gastric vessels (RR 6.82, 2.12 to 21.90) and revisional surgery
(RR 3.69, 1.73 to 7.87) correlated with delayed gastric emptying. In
multivariable analysis, division of short gastric vessels (RR 6.27, 1.85 to
21.26) and revisional surgery (RR 6.19, 1.32 to 28.96) were independently
associated with delayed gastric emptying. Delayed gastric emptying correlated
with adverse gastrointestinal symptomatology, including higher rates of bloating,
nausea, vomiting and anorexia, as well as reduced patient satisfaction with the
operation and recovery. Conclusion: Delayed gastric emptying following large
hiatus hernia repair is common and associated with adverse symptoms and reduced
patient satisfaction. Division of short gastric vessels and revisional surgery
were independently associated with its occurrence.
PMID- 29951610
TI - Experimental evaluation of liver regeneration patterns and liver function
following ALPPS.
AB - Background: The underlying mechanism of liver regeneration after Associating
Liver Partition and Portal vein ligation (PVL) for Staged hepatectomy (ALPPS) is
still unclear. The aim of this study was to evaluate the relationship between
future liver remnant (FLR) volume, liver regeneration characteristics and
restoration of function in an experimental model of ALPPS. Methods: An ALPPS
model in rats was developed with selective PVL, parenchymal transection and
partial hepatectomy (step 1), followed by resection of the liver (step 2). Three
different ALPPS groups with FLR sizes of 30, 20 and 10 per cent of total liver
volume were compared with sham-operated controls and animals undergoing resection
of left lateral lobe and 90 per cent PVL with respect to morbidity, mortality,
liver regeneration and function. Results: Three of 15 animals that had ALPPS with
10 per cent FLR (ALPPS10) died after step 1. Ascites developed in two of five
rats that had ALPPS with 20 per cent FLR and in three of four animals in the
ALPPS10 group after step 2. Although the relative increments in FLR size and
growth rates were highest in the ALPPS groups, small FLR size was associated with
a sustained increase in levels of serum aminotransferases and bilirubin, a lower
albumin concentration, severe sinusoidal injury, increased expression of
proliferation markers and increased activation of hepatic progenitor cells after
step 2. Conclusion: There is discordance between FLR volume increase and
functional restoration after the ALPPS procedure.
PMID- 29951611
TI - Systematic review of clinical practice guidelines in kidney transplantation.
AB - Background: Clinical practice guidelines (CPGs) are widely used to inform the
development of protocols for clinical management. Previous work has demonstrated
that the quality of CPGs varies widely. This systematic review aimed to determine
the quality of CPGs in kidney transplantation in the UK. Methods: CPGs in kidney
transplantation published between 2010 and 2017 were identified through searches
of MEDLINE, NHS NICE Evidence, and websites of relevant UK societies. Using the
Appraisal of Guidelines for Research and Evaluation (AGREE) II tool, three
appraisers rated the quality of CPGs across six domains, the overall quality of
each CPG, and whether it should be recommended for future use. Domain scores were
calculated, and inter-rater reliability using the intraclass correlation
coefficient (ICC) was reported. Results: Thirteen CPGs met the inclusion
criteria. The domain 'clarity of presentation' scored highest, followed closely
by 'scope and purpose'. The poorest scoring domains were 'applicability' and
'editorial independence'. Editorial independence also had the widest range of
scores. Of the 13 CPGs, one was not recommended for future use, seven were
recommended for use with modifications, and five for future use with no need for
modification. Mean overall CPG quality was 5 (range 3-6) of a maximum score of 7,
and mean inter-rater reliability was substantial with an ICC of 0.71. Conclusion:
UK CPGs scored satisfactorily, although with wide variation in how well each
domain scored both within and across CPGs. The quality of UK CPGs can still be
improved.
PMID- 29951613
TI - Regional variation in immediate breast reconstruction in Australia.
AB - Background: Breast reconstruction following mastectomy has proven benefits and is
the standard of care in many high-income countries. This audit documented
regional variation in immediate breast reconstruction rates across Australia.
Methods: The Breast Surgeons of Australia and New Zealand (BreastSurgANZ) Quality
Audit database and geospatial software were used to model the distribution of
breast reconstructions performed on women having mastectomy in Australia in 2013.
Geospatial mapping identified the distribution of these procedures in relation to
the Greater Capital City Statistical Areas (GCCSAs) of the five largest states.
Data were analysed using chi2 tests of independence and an independent-samples t
test. Results: Of 3786 patients having a mastectomy, 692 underwent breast
reconstruction of which 679 (98.1 per cent) were immediate reconstructions. Rates
of reconstruction differed significantly between jurisdictions (chi2 = 164.90),
and were significantly higher in GCCSAs (chi2 = 144.60) and private hospitals
(chi2 = 50.72) (all P < 0.001). Immediate breast reconstruction was not reported
for 43.8 per cent of hospitals where mastectomy was conducted by members of
BreastSurgANZ, including 29.8 per cent of hospitals within GCCSAs. A wider age
range of women appeared to have had immediate reconstructions at hospitals within
GCCSAs, although the difference in mean age between regions was not significant.
Immediate breast reconstruction was considerably less likely to be performed in
women who lived in areas of lower to mid socioeconomic status. Conclusion:
Variations in the rate of immediate breast reconstruction may not be purely
resource-driven.
PMID- 29951612
TI - Systematic review of psychological, emotional and behavioural impacts of surgical
incidents on operating theatre staff.
AB - Background: Adverse surgical incidents affect both patients and health
professionals. This study sought to explore the effect of surgical incidents on
operating theatre staff and their subsequent behaviours. Methods: Eligible
studies were primary research or reviews that focused on the effect of incidents
on operating theatre staff in primary, secondary or tertiary care settings.
MEDLINE, Embase, CINALH and PsycINFO were searched. A data extraction form was
used to capture pertinent information from included studies and the Critical
Appraisal Skills Programme (CASP) tool to appraise their quality. PRISMA-P
reporting guidelines were followed and the review is registered with PROSPERO.
Results: A total of 3918 articles were identified, with 667 duplicates removed
and 3230 excluded at the title, abstract and full-text stages. Of 21 included
articles, eight focused on the impact of surgical incidents on surgeons and
anaesthetists. Only two involved theatre nurses and theatre technicians. Five key
themes emerged: the emotional impact on health professionals, organization
culture and support, individual coping strategies, learning from surgical
complications and recommended changes to practice. Conclusion: Health
professionals suffered emotional distress and often changed their behaviour
following a surgical incident. Both organizations and individual clinicians can
do a great deal to support staff in the aftermath of serious incidents.
PMID- 29951614
TI - Mortality related to primary bariatric surgery in England.
AB - Background: Bariatric surgery is an accepted treatment option for severe obesity.
Previous analysis of the independently collected Hospital Episode Statistics
(HES) data for outcomes after bariatric surgery demonstrated a 30-day
postoperative mortality rate of 0.3 per cent in the English National Health
Service (NHS). However, there have been no published mortality data for bariatric
procedures performed since 2008. This study aimed to assess mortality related to
bariatric surgery in England from 2009. Methods: HES data were used to identify
all patients who had primary bariatric surgery from 2009 to 2016. Clinical codes
were used selectively to identify all primary bariatric procedures but exclude
revision or conversion procedures and operations for malignant or other benign
disease. The primary outcome measures were HES in-hospital and Office for
National Statistics (ONS) 30-day mortality after discharge. Results: A total of
41 241 primary bariatric procedures were carried out in the NHS between 2009 and
2016, with 29 in-hospital deaths (0.07 per cent). The 30-day mortality rate after
discharge was 0.08 per cent (32 of 41 241). Both the in-hospital and 30-day
mortality rates after discharge demonstrated a downward trend over the study
period. Conclusion: Overall in-hospital and 30-day mortality rates remain very
low after primary bariatric surgery. An increased uptake of bariatric surgery
within the English NHS has been safe.
PMID- 29951615
TI - Systematic review and meta-analysis of frailty as a predictor of morbidity and
mortality after major abdominal surgery.
AB - Background: Frailty is associated with poor prognosis, but the multitude of
definitions and scales of assessment makes the impact on outcomes difficult to
assess. The aim of this study was to quantify the effect of frailty on
postoperative morbidity and mortality, and long-term mortality after major
abdominal surgery, and to evaluate the performance of different frailty metrics.
Methods: An extended literature search was performed to retrieve all original
articles investigating whether frailty could affect outcomes after elective major
abdominal surgery in adult populations. All possible definitions of frailty were
considered. A random-effects meta-analysis was carried out for all outcomes of
interest. For postoperative morbidity and mortality, overall effect sizes were
estimated as odds ratios (OR), whereas the hazard ratio (HR) was calculated for
long-term mortality. The potential effect of the number of domains of the frailty
indices was explored through meta-regression at moderator analysis. Results: A
total of 35 studies with 1 153 684 patients were analysed. Frailty was associated
with a significantly increased risk of postoperative major morbidity (OR 2.56, 95
per cent c.i. 2.08 to 3.16), short-term mortality (OR 5.77, 4.41 to 7.55) and
long-term mortality (HR 2.71, 1.63 to 4.49). All domains were significantly
associated with the occurrence of postoperative major morbidity, with ORs ranging
from 1.09 (1.00 to 1.18) for co-morbidity to 2.52 (1.32 to 4.80) for sarcopenia.
No moderator effect was observed according to the number of frailty components.
Conclusion: Regardless of the definition and combination of domains, frailty was
significantly associated with an increased risk of postoperative morbidity and
mortality after major abdominal surgery.
PMID- 29951616
TI - Systematic review assessing the measurement properties of patient-reported
outcomes for venous leg ulcers.
AB - Background: A variety of instruments have been used to assess outcomes for
patients with venous leg ulcers. This study sought to identify, evaluate and
recommend the most appropriate patient-reported outcome measures (PROMs) for
English-speaking patients with venous leg ulcers. Methods: This systematic review
used a two-stage search approach. Electronic searches of major databases
including MEDLINE were completed in October 2015, and then updated in July 2016.
Additional studies were identified from citation checking. Study selection, data
extraction and quality assessment were undertaken independently by at least two
reviewers. Evaluation and summary of measurement properties of identified PROMs
were done using standard and adapted study-relevant criteria. Results: Ten
studies with data for four generic PROMS and six condition-specific measures were
identified. No generic PROM showed adequate content and criterion validity;
however, the EuroQoL Five Dimensions (EQ-5DTM), Nottingham Health Profile (NHP)
and 12-item Short-Form Health Survey (SF-12(r)) had good acceptability. In
general, the EQ-5DTM showed poor responsiveness in patients with venous leg
ulcers. Most condition-specific PROMs demonstrated poor criterion and construct
validity. Overall, there was some evidence of internal consistency for the Venous
Leg Ulcer Quality of Life (VLU-QoL) and the Sheffield Preference-based Venous
Ulcer questionnaire (SPVU-5D). Test-retest reliability was satisfactory for the
Venous Leg Ulcer Self-Efficacy Tool (VeLUSET). Conclusion: The NHP and VLU-QoL
questionnaire seemed the most suitable PROMs for use by clinicians. However, a
valid condition-specific PROM is still required.
PMID- 29951617
TI - Trends in breast reconstruction practices in a specialized breast tertiary
referral centre.
AB - Background: Breast reconstruction is an important component of multidisciplinary
breast cancer management. The practice of breast reconstruction after mastectomy
has evolved significantly in the past decade as a result of both increasing
mastectomy rates and advances in reconstructive strategy. These changes have
significantly influenced the contemporary surgical management of breast cancer.
The aim of this study was to examine trends in breast reconstruction after
mastectomy in an Irish population. Methods: Data were reviewed from a database of
all patients who had mastectomy with or without breast reconstruction at Galway
University Hospital, a tertiary breast cancer referral centre, between 2004 and
2014. Trends in breast reconstruction after mastectomy were explored with respect
to patient demographics, clinicopathological features, and neoadjuvant and
adjuvant therapy. Results: Of 1303 patients who underwent mastectomy during
interval studied, 706 (54.2 per cent) had breast reconstruction after mastectomy.
In 629 patients (89.1 per cent), breast reconstruction was performed in the
immediate setting. Reconstruction rates increased over time from 20.5 per cent in
2004 to 44.7 per cent in 2014. Reconstruction was more commonly performed in
younger patients and those with benign, in situ and early-stage disease. A
negative relationship between radiotherapy and reconstruction was observed. A
pedicled flap with or without an implant was the most commonly used
reconstructive approach in patients receiving radiotherapy. Conclusion: Breast
reconstruction after mastectomy has become the standard of care in the surgical
treatment of breast cancer. Recent trends show a transition favouring implant
based approaches.
PMID- 29951618
TI - Weekend effect in non-elective abdominal aortic aneurysm repair.
AB - Background: The 'weekend effect' describes the phenomenon where patient outcomes
appear worse for those admitted at the weekend. It has been used recently to
justify significant changes in UK health policy. Recent evidence has suggested
that the effect may be due to a combination of inadequate correction for
confounding factors and inaccurate coding. The effects of these factors were
investigated in patients with acute abdominal aortic aneurysm (AAA). Methods:
Patients undergoing non-elective AAA repair entered into the UK National Vascular
Registry from January 2013 until December 2015 were included in a case-control
study. The patients were divided according to whether they were treated during
the week (Monday 08.00 hours to Friday 17.00 hours) or at the weekend. Data
extracted included demographics, co-morbidities, preoperative medications and
baseline blood test results, as well as outcomes. Coding issues were investigated
by looking at patients treated for ruptured, symptomatic or asymptomatic AAA
within the non-elective cohort. The primary outcome was in-hospital mortality.
Secondary outcomes included length of inpatient stay, and cardiac, respiratory
and renal complications. Results: The mortality rate appeared to be higher at the
weekend (odds ratio (OR) 1.69, 95 per cent c.i. 1.47 to 1.94; P < 0.001), but
this effect disappeared when confounding factors and coding issues were corrected
for (corrected OR for ruptured AAA 1.09, 0.92 to 1.29; P = 0.330). Differences in
outcomes were similar for prolonged length of hospital stay (uncorrected OR 1.21,
95 per cent c.i. 1.06 to 1.37, P = 0.005; corrected OR for ruptured AAA 1.06,
0.91 to 1.10, P = 0.478), and morbidity outcomes. Conclusion: After appropriate
correction for confounding factors and coding effects, there was no evidence of a
significant weekend effect in the treatment of non-elective AAA in the UK.
PMID- 29951619
TI - Multicentre observational study of quality of life after surgical palliation of
malignant gastric outlet obstruction for gastric cancer.
AB - Background: Quality of life (QoL) is a key component in decision-making for
surgical palliation, but QoL data in association with surgical palliation in
advanced gastric cancer are scarce. The aim of this multicentre observational
study was to examine the impact of surgical palliation on QoL in advanced gastric
cancer. Methods: The study included patients with gastric outlet obstruction
caused by incurable advanced primary gastric cancer who had no oral intake or
liquid intake only. Patients underwent palliative distal/total gastrectomy or
bypass surgery at the physician's discretion. The primary endpoint was change in
QoL assessed at baseline, 14 days, 1 month and 3 months following surgical
palliation by means of the EuroQoL Five Dimensions (EQ-5DTM) questionnaire and
the European Organisation for Research and Treatment of Cancer Quality of Life
Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were
postoperative improvement in oral intake and surgical complications. Results:
Some 104 patients (23 distal gastrectomy, 9 total gastrectomy, 70
gastrojejunostomy, 2 exploratory laparotomy) were enrolled from 35 institutions.
The mean EQ-5DTM utility index scores remained consistent, with a baseline score
of 0.74 and the change from baseline within +/- 0.05. Gastric-specific symptoms
showed statistically significant improvement from baseline. The majority of
patients were able to eat solid food 2 weeks after surgery and tolerated it
thereafter. The rate of overall morbidity of grade III or more according to the
Clavien-Dindo classification was 9.6 per cent (10 patients) and the 30-day
postoperative mortality rate was 1.9 per cent (2 patients). Conclusion: In
patients with gastric outlet obstruction caused by advanced gastric cancer,
surgical palliation maintained QoL while improving solid food intake, with
acceptable morbidity for at least the first 3 months after surgery. Registration
number 000023494 (UMIN Clinical Trials Registry).
PMID- 29951620
TI - Relationship between intra-abdominal hypertension, outcome and the revised
Atlanta and determinant-based classifications in acute pancreatitis.
AB - Background: The aim of this study was to analyse the relationship between intra
abdominal hypertension (IAH) and severity of acute pancreatitis (AP) measured by
the revised Atlanta classification (RAC) and determinant-based classification
(DBC). Secondary objectives were to assess IAH as a predictor of morbidity and
mortality in the ICU. Methods: This prospective international observational study
included patients admitted to the ICU with AP and at least one organ failure.
Information was collected on demographics, severity scores at admission using RAC
and DBC, organ failure, mechanical ventilation, continuous renal replacement
therapy (CRRT), surgery and mortality. Maximum intra-abdominal pressure (IAP)
during ICU stay was used for analysis. Results: Some 374 patients were included.
The hospital mortality rate was 28.9 per cent. IAP was measured in 301 patients
(80.5 per cent), of whom 274 (91.0 per cent) had IAH and 103 (34.2 per cent)
acute compartment syndrome. A higher IAH grade was more likely in patients with
severe AP (42 per cent for grade I versus 84 per cent for grade IV) and acute
critical pancreatitis (9 versus 25 per cent; P = 0.001). Compared with grade I
IAH, patients with grade IV had more infected necrosis (16 versus 28 per cent; P
= 0.005), need for surgery (27 versus 50 per cent; P = 0.006), mechanical
ventilation (53 versus 84 per cent; P = 0.007) and requirement for CRRT (22
versus 66 per cent; P < 0.001). IAH predicted shock (area under receiver
operating characteristic (ROC) curve (AUC) 0.79, 95 per cent c.i. 0.73 to 0.84),
respiratory failure (AUC 0.82, 0.77 to 0.87), renal failure (AUC 0.93, 0.89 to
0.96) and mortality (AUC 0.89, 0.86 to 0.93). Conclusion: IAH was associated with
severity of AP classified according to both RAC and DBC systems. IAP grade can
predict outcome of AP during ICU stay.
PMID- 29951622
TI - Effects of patient factors on inpatient mortality after complex liver, pancreatic
and gastric resections.
AB - Background: There is mixed evidence that patients who receive care in hospitals
with a low case volume for complex gastrointestinal and hepatobiliary operations
have an increased risk of inpatient death. Methods: A retrospective cohort study
was performed of patients who had complex gastrointestinal and hepatobiliary
operations in the Healthcare Cost and Utilization Project 2012 National Inpatient
Sample. Multivariable weighted hierarchical generalized linear models were used
to test the relationship between hospital case volume and probability of
inpatient death, with detailed adjustments for the concurrent effects of
differences in associated patient co-morbidities. Results: A total of 8260
pancreaticoduodenectomies, 2750 major hepatectomies and 3250 total gastrectomies
were identified. Inpatient death occurred in 3.6 per cent of patients after
pancreaticoduodenectomy, 4.9 per cent after major hepatectomy and 4.6 per cent
after total gastrectomy. Mean hospital case volume was 50.6 (median 40) for
pancreaticoduodenectomy, 23.6 (median 15) for major hepatectomy, 15.1 (median 10)
for total gastrectomy and 70.2 (median 50) for any of the three operations.
Hospital case volume was not a statistically significant predictor of mortality
after any operation (all P >= 0.188). Patient characteristics including age and
co-morbidity were highly significant predictors of mortality (P < 0.001). No
significant improvements in model performance were obtained by adding hospital
case volume to any model that already included adjustments for patient-level
differences in age and co-morbid disease, for any functional format (P >= 0.146
for all C statistic differences from baseline). Conclusion: Patient co-morbidity,
not hospital case volume, was associated with significant differences in
inpatient mortality following complex gastric, pancreatic and hepatobiliary
resections.
PMID- 29951621
TI - Patterns of recurrence in oesophageal cancer following oesophagectomy in the era
of neoadjuvant chemotherapy.
AB - Background: Tumour recurrence following oesophagectomy for oesophageal cancer is
common despite neoadjuvant treatment. Understanding patterns of recurrence and
risk factors associated with locoregional and systemic recurrence might influence
future treatment strategies. Methods: This was a cohort study involving patients
undergoing resection for adenocarcinoma or squamous cell carcinoma of the
oesophagus between 2000 and 2014. Clinicopathological factors associated with
locoregional and systemic recurrence were analysed using multivariable logistic
regression to determine odds ratios (ORs) and 95 per cent confidence intervals.
Results: Some 698 patients were identified. Lymphovascular invasion (OR 2.09, 95
per cent c.i. 1.18 to 3.71) and preoperative stenting (OR 3.70, 1.34 to 10.23)
were independent risk factors for isolated locoregional recurrence. Pathological
nodal disease in patients with pT1-2 (pN1: OR 2.72, 1.35 to 5.48; pN2-3: OR 5.00,
2.35 to 10.66) or pT3-4 (pN1: OR 3.03, 1.51 to 6.07; pN2-3: OR 5.75, 3.15 to
10.49) disease predisposed to systemic recurrence. Poor or no response to
chemotherapy was also an independent risk factor for isolated systemic recurrence
(OR 1.85, 1.05 to 3.26). A positive resection margin (R1 resection) was not
associated with a significantly increased risk of isolated locoregional
recurrence (OR 1.37, 0.81 to 2.33). Conclusion: These findings confirm that
oesophageal adenocarcinoma is frequently a systemic disease. Understanding the
key predictors of local and systemic recurrence may facilitate the tailoring of
oncological therapies to the individual patient.
PMID- 29951623
TI - Impact of restenting for recurrent colonic obstruction due to tumour ingrowth.
AB - Background: Endoscopic stenting is used to palliate malignant large bowel
obstruction. A proportion of patients will develop recurrent obstruction due to
tumour ingrowth and require reintervention. This study aimed to assess the
outcome (clinical success and complication rates) of endoscopic reintervention
compared with surgical intervention in patients with stent obstruction due to
tumour ingrowth. Methods: This was an observational study using data from a
database of patients who underwent palliative colonic stenting between January
1998 and March 2017 at Christchurch Public Hospital. Results: A total of 190
patients underwent colonic stent insertion, for palliation in 182 cases.
Reintervention was performed in 55 (30.2 per cent). Thirty-one patients (17.0 per
cent) developed obstruction within the stent at a median of 4.6 (i.q.r. 2.3-7.7)
months after the procedure. Of these, 21 had endoscopic restenting and ten
underwent surgery. Restenting had technical and clinical success rates of 100 per
cent, and involved a significantly shorter length of stay compared with surgery
(median 2 (i.q.r. 1-4) versus 11 (6-19) days respectively; P = 0.006). Seven of
the 21 patients in the restented group underwent a third palliative intervention.
The overall stoma rate in the restented group was significantly lower than that
in the surgical group (4 of 21 versus 10 of 10; P < 0.001). There was no
difference in complications or survival between the two groups. Conclusion: Among
palliative patients who develop malignant stent obstruction, endoscopic
restenting had a high chance of technical success. It resulted in a shorter
hospital stay and lower stoma rate than those seen after surgery.
PMID- 29951624
TI - Systematic review and meta-analysis comparing outcomes following orchidopexy for
cryptorchidism before or after 1 year of age.
AB - Background: Current guidelines recommend orchidopexy for cryptorchidism by 12
months of age, yet this is not universally adhered to. The aim of this systematic
review and meta-analysis was to compare outcomes between orchidopexies performed
before and after 1 year of age. Methods: MEDLINE and Embase were searched
(September 2015) using terms relating to cryptorchidism, orchidopexy and the
outcomes of interest. Studies were eligible for inclusion if they compared
orchidopexy at less than 1 year of age (early) with orchidopexy at 1 year or more
of age (delayed) and reported the primary outcome (testicular atrophy) or one of
the secondary outcomes (fertility potential, postoperative complication,
malignancy). Studies were excluded when more than 50 per cent of infants had
intra-abdominal testes, or the population included infants with disorders of
sexual differentiation. Additional studies were identified through reference list
searching. Unpublished data were sought from the ORCHESTRA study investigators.
Results: Fifteen eligible studies were identified from 1387 titles. There was no
difference in atrophy rate between early orchidopexy and delayed orchidopexy
(risk ratio 0.64, 95 per cent c.i. 0.25 to 1.66; 912 testes). Testicular volume
was greater (mean difference 0.06 (95 per cent c.i. 0.01 to 0.10) ml; 346 testes)
and there were more spermatogonia per tubule (mean difference 0.47 (0.31 to
0.64); 382 testes) in infants undergoing early orchidopexy, with no difference in
complication rate (risk ratio 0.68, 0.27 to 1.68; 426 testes). No study reported
malignancy rate. Conclusion: Atrophy and complication rates do not appear
different between early and delayed orchidopexy, and fertility potential may be
better with early orchidopexy. Imprecision of the available data limits the
robustness of these conclusions.
PMID- 29951625
TI - Predictive performance of factors associated with malignancy in intraductal
papillary mucinous neoplasia of the pancreas.
AB - Background: Estimation of the risk of malignancy in intraductal papillary
mucinous neoplasia (IPMN) of the pancreas is a clinical challenge. Several
routinely used clinical factors form the basis of the current consensus
guidelines. This study aimed to determine the predictive values of the most
commonly assessed risk factors. Methods: A meta-analysis of individual risk
factors of malignancy in IPMN was performed. Contingency tables were derived from
these data, and sensitivity, specificity, negative and positive predictive
values, and diagnostic odds ratios (DOR) were determined. Hierarchical summary
receiver operating characteristic (HSROC) curves for each factor were calculated
and the respective area under the curve (AUC) was assessed. Results: A total of
3443 studies were screened initially. Analysis of recent literature revealed 60
studies with 13 relevant risk factors including clinical, serological and
radiological parameters. The largest area under the HSROC curve was found for
weight loss (0.84) and jaundice/raised bilirubin level (0.80), followed by
increased carcinoembryonic antigen (CEA) (0.79) or carbohydrate antigen (CA) 19-9
(0.78) levels. The most sensitive factors were patient age (71 per cent) and
mural nodules (65 per cent), and jaundice/raised bilirubin level (97 per cent)
and increased CEA level (95 per cent) were most specific. None of the analysed
factors reached a positive or negative level of prediction beyond 90 per cent.
Conclusion: None of the established criteria safely distinguishes malignant from
non-malignant lesions.
PMID- 29951626
TI - Assessing the cost of laparotomy at a rural district hospital in Rwanda using
time-driven activity-based costing.
AB - Background: In low- and middle-income countries, the majority of patients lack
access to surgical care due to limited personnel and infrastructure. The Lancet
Commission on Global Surgery recommended laparotomy for district hospitals.
However, little is known about the cost of laparotomy and associated clinical
care in these settings. Methods: This costing study included patients with acute
abdominal conditions at three rural district hospitals in 2015 in Rwanda, and
used a time-driven activity-based costing methodology. Capacity cost rates were
calculated for personnel, location and hospital indirect costs, and multiplied by
time estimates to obtain allocated costs. Costs of medications and supplies were
based on purchase prices. Results: Of 51 patients with an acute abdominal
condition, 19 (37 per cent) had a laparotomy; full costing data were available
for 17 of these patients, who were included in the costing analysis. The total
cost of an entire care cycle for laparotomy was US$1023.40, which included
intraoperative costs of US$427.15 (41.7 per cent) and preoperative and
postoperative costs of US$596.25 (58.3 per cent). The cost of medicines was
US$358.78 (35.1 per cent), supplies US$342.15 (33.4 per cent), personnel
US$150.39 (14.7 per cent), location US$89.20 (8.7 per cent) and hospital indirect
cost US$82.88 (8.1 per cent). Conclusion: The intraoperative cost of laparotomy
was similar to previous estimates, but any plan to scale-up laparotomy capacity
at district hospitals should consider the sizeable preoperative and postoperative
costs. Although lack of personnel and limited infrastructure are commonly cited
surgical barriers at district hospitals, personnel and location costs were among
the lowest cost contributors; similar location-related expenses at tertiary
hospitals might be higher than at district hospitals, providing further support
for decentralization of these services.
PMID- 29951627
TI - Effect of informed consent on patients undergoing gastrointestinal surgery and
living donor liver transplantation and on their relatives in a developing
country.
AB - Background: Informed consent is a systematic process for obtaining permission
before conducting a healthcare intervention. In a developing country, gaining
informed consent is generally perceived to be a ritual only to comply with legal
requirements. The present study examined this by assessing the process of
informed consent in patients undergoing gastrointestinal surgery or living donor
liver transplantation (LDLT) and their relatives, based on their comprehension
and overall satisfaction, in India. Methods: All patients undergoing any
gastrointestinal surgery or LDLT procedure between August 2015 and July 2016 and
their relatives were included, and were administered a structured questionnaire 5
days after the procedure. Results: The majority of patients (94.2 per cent) could
recall the nature of their disease, the surgery performed (81.6 per cent) and
anticipated complications (55.6 per cent). Among their relatives, these
proportions were 97.8, 87.3 and 58.5 per cent respectively. Recall was associated
with age, occupation and education among both patients and relatives. Patients
undergoing LDLT, their donors and their relatives had better recall than those
who had other gastrointestinal procedures (P < 0.001). Many patients found the
process of informed consent useful and reassuring. Conclusion: The details and
risks of an operation were understood by most of the patients, especially those
undergoing liver transplantation. Patients from developing countries can
generally understand 'informed consent', and value it.
PMID- 29951628
TI - Systematic review of methods for quantifying teamwork in the operating theatre.
AB - Background: Teamwork in the operating theatre is becoming increasingly recognized
as a major factor in clinical outcomes. Many tools have been developed to measure
teamwork. Most fall into two categories: self-assessment by theatre staff and
assessment by observers. A critical and comparative analysis of the validity and
reliability of these tools is lacking. Methods: MEDLINE and Embase databases were
searched following PRISMA guidelines. Content validity was assessed using
measurements of inter-rater agreement, predictive validity and multisite
reliability, and interobserver reliability using statistical measures of inter
rater agreement and reliability. Quantitative meta-analysis was deemed
unsuitable. Results: Forty-eight articles were selected for final inclusion; self
assessment tools were used in 18 and observational tools in 28, and there were
two qualitative studies. Self-assessment of teamwork by profession varied with
the profession of the assessor. The most robust self-assessment tool was the
Safety Attitudes Questionnaire (SAQ), although this failed to demonstrate
multisite reliability. The most robust observational tool was the Non-Technical
Skills (NOTECHS) system, which demonstrated both test-retest reliability (P >
0.09) and interobserver reliability (Rwg = 0.96). Conclusion: Self-assessment of
teamwork by the theatre team was influenced by professional differences.
Observational tools, when used by trained observers, circumvented this.
PMID- 29951629
TI - Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in
pancreatic ductal adenocarcinoma.
AB - Background: Neoadjuvant therapy may increase the rate of radical tumour resection
in patients with pancreatic cancer. Its impact on tumour recurrence has not been
investigated fully. This study aimed to assess the impact of neoadjuvant therapy
on patterns of recurrence. Methods: A systematic review was performed of articles
identified through the PubMed, Scopus, Embase, Ovid and Google Scholar databases
that analysed the relationship between neoadjuvant therapy and recurrence
published to January 2016. The main endpoint was overall tumour recurrence. Other
endpoints included local recurrence, any kind of distant, hepatic, pulmonary or
peritoneal metastasis. Results: A total of 4257 citations were reviewed. Twelve
observational studies comprising 1365 patients were analysed. Neoadjuvant therapy
significantly reduced the risk of overall (risk ratio (RR) 0.82, 95 per cent c.i.
0.74 to 0.90; P < 0.001) and local (RR 0.42, 0.32 to 0.55; P < 0.001) recurrence.
Neoadjuvant therapy did not reduce the risk of any kind of distant (RR 1.02, 0.91
to 1.14; P = 0.78), hepatic (RR 0.86, 0.68 to 1.10; P = 0.23), pulmonary (RR
0.99, 0.37 to 2.66; P = 0.98) or peritoneal (RR 0.88, 0.57 to 1.38; P = 0.58)
metastasis. Conclusion: Neoadjuvant therapy reduced the risk of local recurrence
but not that of distant metastasis.
PMID- 29951630
TI - Nationwide study of patients with head and neck paragangliomas carrying SDHB
germline mutations.
AB - Background: Germline mutations in the succinate dehydrogenase B (SDHB) gene
predispose to hereditary paraganglioma (PGL) syndrome type 4. The aim of this
study was to evaluate the clinical characteristics and outcome of treatment
strategies for patients with head and neck paraganglioma (HNPGL) carrying SDHB
germline mutations. Methods: This was a retrospective evaluation of patients with
HNPGL carrying SDHB germline mutations in the Netherlands. Results: In a Dutch
nationwide cohort study of SDHB germline mutation carriers, 54 patients with a
total of 62 HNPGLs were identified. Forty-one of 54 patients (76 per cent)
visited the outpatient clinic because of associated complaints. Eight patients
(15 per cent) had multiple PGLs. One patient (2 per cent) developed a
phaeochromocytoma and three (6 per cent) developed a malignant PGL. Twenty-seven
patients (50 per cent) had an operation for their HNPGL and 15 (28 per cent)
received radiotherapy. Three patients with HNPGL (6 per cent) were diagnosed with
additional non-paraganglionic tumours. Conclusion: If an SDHB germline mutation
is identified in a patient with HNPGL, the clinician should be aware of the
variable manifestations of the SDHB-linked tumour syndrome, the risk of
catecholamine excess, concurrent phaeochromocytoma, and association with non
paraganglionic tumours.
PMID- 29951631
TI - Effects of transcranial direct-current stimulation on laparoscopic surgical skill
acquisition.
AB - Background: Changes in medical education may limit opportunities for trainees to
gain proficiency in surgical skills. Transcranial direct-current stimulation
(tDCS) can augment motor skill learning and may enhance surgical procedural skill
acquisition. The aim of this study was to determine the effects of tDCS on
simulation-based laparoscopic surgical skill acquisition. Methods: In this double
blind, sham-controlled randomized trial, participants were randomized to receive
20 min of anodal tDCS or sham stimulation over the dominant primary motor cortex,
concurrent with Fundamentals of Laparoscopic Surgery simulation-based training.
Primary outcomes of laparoscopic pattern-cutting and peg transfer tasks were
scored at baseline, during repeated performance over 1 h, and again at 6 weeks.
Intent-to-treat analysis examined the effects of treatment group on skill
acquisition and retention. Results: Of 40 participants, those receiving tDCS
achieved higher mean(s.d.) final pattern-cutting scores than participants in the
sham group (207.6(30.0) versus 186.0(32.7) respectively; P = 0.022). Scores were
unchanged at 6 weeks. Effects on peg transfer scores were not significantly
different (210.2(23.5) in the tDCS group versus 201.7(18.1) in the sham group; P
= 0.111); the proportion achieving predetermined proficiency levels was higher
for tDCS than for sham stimulation. Procedures were well tolerated with no
serious adverse events and no decreases in motor measures. Conclusion: The
addition of tDCS to laparoscopic surgical training may enhance skill acquisition.
Trials of additional skills and translation to non-simulated performance are
required to determine the potential value in medical education and impact on
patient outcomes. Registration number: NCT02756052 (https://clinicaltrials.gov/).
PMID- 29951632
TI - Systematic review of the cost-effectiveness of preoperative antibiotic
prophylaxis in reducing surgical-site infection.
AB - Background: Surgical-site infections (SSIs) increase the length of hospital
admission and costs. SSI prevention guidelines include preoperative antibiotic
prophylaxis. This review assessed the reporting quality and cost-effectiveness of
preoperative antibiotics used to prevent SSI. Methods: PubMed, Web of Science,
Cumulative Index to Nursing and Allied Health Literature, Index of Economic
Articles (EconLit), Database of Abstracts of Reviews of Effect (including the
National Health Service Economic Evaluation Database) and Cochrane Central
databases were searched systematically from 1970 to 2017 for articles that
included costs, preoperative antibiotic prophylaxis and SSI. Included were RCTs
and quasi-experimental studies conducted in Organisation for Economic Co
operation and Development countries with participants aged at least 18 years and
published in English. Two reviewers assessed eligibility, with inter-rater
reliability determined by Cohen's kappa statistic. The Consolidated Health
Economic Evaluation and Reporting Standards (CHEERS) and modified Drummond
checklists were used to assess reporting and economic quality. Study outcomes and
characteristics were extracted, and incremental cost-effectiveness ratios were
calculated, with costs adjusted to euros (2016) (?1 = US $1.25; L1 sterling =
?1.28). Results: Twelve studies published between 1988 and 2014 were included
from 646 records identified; nine were RCTs, two were nested within RCTs and one
was a retrospective chart review. Study quality was highest in the nested
studies. Cephalosporins (first, second and third generation) were the most
frequent prophylactic interventions. Eleven studies demonstrated clinically
effective interventions; ten were cost-effective (the intervention was dominant);
in one the intervention was dominated by the control; and in one the intervention
was more effective and more expensive than the control. Conclusion: Preoperative
antibiotic prophylaxis does reduce SSI, costs to hospitals and health providers,
but the reporting of economic methods in RCTs is not standardized. Routinely
nesting economic methods in RCTs would improve economic evaluations and ensure
appropriate selection of prophylactic antibiotics.
PMID- 29951633
TI - Pilot feasibility randomized clinical trial of negative-pressure wound therapy
versus usual care in patients with surgical wounds healing by secondary
intention.
AB - Background: Surgical wounds healing by secondary intention (SWHSI) are
increasingly being treated with negative-pressure wound therapy (NPWT) despite a
lack of high-quality research evidence regarding its clinical and cost
effectiveness. This pilot feasibility RCT aimed to assess the methods for and
feasibility of conducting a future definitive RCT of NPWT for the treatment of
SWHSI. Methods: Eligible consenting adult patients receiving care at the study
sites (2 acute and 1 community) and with a SWHSI appropriate for NPWT or wound
dressing treatment were randomized 1 : 1 centrally to receive NPWT or usual care
(no NPWT). Participants were followed up every 1-2 weeks for 3 months.
Feasibility (recruitment rate, time to intervention delivery) and clinical (time
to wound healing) outcomes were assessed. Results: A total of 248 participants
were screened for eligibility; 40 (16.1 per cent) were randomized, 19 to NPWT and
21 to usual care. Twenty-four of the 40 wounds were located on the foot.
Participants received NPWT for a median of 18 (range 0-72) days. Two participants
in the NPWT group never received the intervention and 14 received NPWT within 48
h of randomization. Five participants in the usual care group received NPWT
during the study. Ten of the 40 wounds were deemed to have healed during the
study. Conclusion: A full-scale RCT to investigate the clinical and cost
effectiveness of NPWT for SWHSI is feasible. This study identified crucial
information on recruitment rates and data collection methods to consider during
the design of a definitive RCT. Registration number: ISRCTN12761776
(http://www.iscrtn.com).
PMID- 29951634
TI - Randomized clinical trial of remote ischaemic preconditioning versus no
preconditioning in the prevention of perioperative myocardial infarction during
open surgery for ruptured abdominal aortic aneurysm.
AB - Background: Remote ischaemic preconditioning (RIPC) has been suggested as a means
of protecting vital organs from reperfusion injury during major vascular surgery.
This study was designed to determine whether RIPC could reduce the incidence of
perioperative myocardial infarction (MI) during open surgery for ruptured
abdominal aortic aneurysm (AAA). Secondary aims were to see if RIPC could reduce
30-day mortality, multiple organ failure, acute intestinal ischaemia, acute
kidney injury and ischaemic stroke. Methods: This randomized, non-blinded
clinical trial was undertaken at three vascular surgery centres in Denmark.
Patients who had open surgery for ruptured AAA were randomized to intervention
with RIPC or control in a 1 : 1 ratio. Postoperative complications and deaths
were registered, and ECG and blood samples were obtained daily during the
hospital stay. Results: Of 200 patients randomized, 142 (72 RIPC, 70 controls)
were included. There was no difference in rates of perioperative MI between the
RIPC and control groups (36 versus 43 per cent respectively), or in rates of
organ failure. However, in the per-protocol analysis 30-day mortality was
significantly reduced in the RIPC group (odds ratio 0.46, 95 per cent c.i. 0.22
to 0.99; P = 0.048). Conclusion: RIPC did not reduce the incidence of
perioperative MI in patients undergoing open surgery for ruptured AAA.
Registration number: NCT00883363 ( http://www.clinicaltrials.gov).
PMID- 29951635
TI - Development of the Surgical Patient safety Observation Tool (SPOT).
AB - Background: A Surgical Patient safety Observation Tool (SPOT) was developed and
tested in a multicentre observational pilot study. The tool enables monitoring
and benchmarking perioperative safety performance across departments and
hospitals, covering international patient safety goals. Methods: Nineteen
perioperative patient safety observation topics were selected from Dutch
perioperative patient safety guidelines, which also cover international patient
safety goals. All items that measured these selected topics were then extracted
from available local observation checklists of the participating hospitals.
Experts individually prioritized the best measurement items per topic in an
initial written Delphi round. The second (face to face) Delphi round resulted in
consensus on the content of SPOT, after which the measurable elements (MEs) per
topic were defined. Finally, the tool was piloted in eight hospitals for
measurability, applicability, improvement potential, discriminatory capacity and
feasibility. Results: The pilot test showed good measurability for all 19 patient
safety topics (range of 8-291 MEs among topics), with good applicability (median
97 (range 11.8-100) per cent). The overall improvement potential appeared to be
good (median 89 (range 72.5-100) per cent), and at topic level the tool showed
good discriminatory capacity (variation 27.5 per cent, range in compliance 72.5
100 per cent). Overall scores showed relatively little variation between the
participating hospitals (variation 13 per cent, range in compliance 83-96 per
cent). All eight auditors considered SPOT a straightforward and easy-to-use
tracer tool. Conclusion: A comprehensive tool to measure safety of care was
developed and validated using a systematic, stepwise method, enabling hospitals
to monitor, benchmark and improve perioperative safety performance.
PMID- 29951636
TI - Incidence of and risk factors for stoma-site incisional herniation after
reversal.
AB - Background: Stoma reversal is often considered a straightforward procedure with
low short-term complication rates. The aim of this study was to determine the
rate of incisional hernia following stoma reversal and identify risk factors for
its development. Methods: This was an observational study of consecutive patients
who underwent stoma reversal between 2009 and 2015 at a teaching hospital.
Patients followed for at least 12 months were eligible. The primary outcome was
the development of incisional hernia at the previous stoma site. Independent risk
factors were assessed using multivariable logistic regression analysis. Results:
After a median follow-up of 24 (range 12-89) months, 110 of 318 included patients
(34.6 per cent) developed an incisional hernia at the previous stoma site. In 85
(77.3 per cent) the hernia was symptomatic, and 72 patients (65.5 per cent)
underwent surgical correction. Higher BMI (odds ratio (OR) 1.12, 95 per cent c.i.
1.04 to 1.21), stoma prolapse (OR 3.27, 1.04 to 10.27), parastomal hernia (OR
5.08, 1.30 to 19.85) and hypertension (OR 2.52, 1.14 to 5.54) were identified as
independent risk factors for the development of incisional hernia at the previous
stoma site. In addition, the risk of incisional hernia was greater in patients
with underlying malignant disease who had undergone a colostomy than in those who
had had an ileostomy (OR 5.05, 2.28 to 11.23). Conclusion: Incisional hernia of
the previous stoma site was common and frequently required surgical correction.
Higher BMI, reversal of colostomy in patients with an underlying malignancy,
stoma prolapse, parastomal hernia and hypertension were identified as independent
risk factors.
PMID- 29951637
TI - Influence of neural monitoring during thyroid surgery on nerve integrity and
postoperative vocal function.
AB - Background: Integrity of the recurrent laryngeal nerve (RLN) and the external
branch of the superior laryngeal nerve (EBSLN) can be checked by intraoperative
nerve monitoring (IONM) after visualization. The aim of this study was to
determine the prevalence and nature of voice dysfunction following thyroid
surgery with routine IONM. Methods: Thyroidectomies were performed with routine
division of strap muscles and nerve monitoring to confirm integrity of the RLN
and EBSLN following dissection. Patients were assessed for vocal function before
surgery and at 1 and 3 months after operation. Assessment included use of the
Voice Handicap Index (VHI) 10, maximum phonation time, fundamental frequency,
pitch range, harmonic to noise ratio, cepstral peak prominence and smoothed
cepstral peak prominence. Results: A total of 172 nerves at risk were analysed in
102 consecutive patients undergoing elective thyroid surgery. In 23.3 per cent of
EBSLNs and 0.6 per cent of RLNs nerve identification required the assistance of
IONM in addition to visualization. Nerve integrity was confirmed during surgery
for 98.8 per cent of EBSLNs and 98.3 per cent of RLNs. There were no differences
between preoperative and postoperative VHI-10 scores. Acoustic voice assessment
showed small changes in maximum phonation time at 1 and 3 months after surgery.
Conclusion: Where there is routine division of strap muscles, thyroidectomy using
nerve monitoring confirmation of RLN and EBSLN function following dissection
results in no clinically significant voice change.
PMID- 29951638
TI - Population-based cohort study on the epidemiology of acute appendicitis in
children in Sweden in 1987-2013.
AB - Background: The long-term incidence of acute appendicitis has been reported to be
declining in Europe and North America. Recent reports, however, indicate
stabilized or even increased rates. The aim of this study was to investigate the
present epidemiology of acute appendicitis and appendicectomy in a population
based cohort of Swedish children. Methods: The Swedish National Patient Register
was queried for all children with acute appendicitis and/or appendicectomy in
1987-2013. Population-based incidence rates were calculated. Rates were age- and
sex-adjusted, and analysed for temporal and regional trends. Results: Some 56 774
children with acute appendicitis were identified, of whom 53 478 (94.2 per cent)
underwent appendicectomy. The incidence rate of acute appendicitis declined by
43.7 per cent over 26 years, from 177.7 to 100.1 per 100 000 person-years between
1987 and 2013. The most significant reduction was for non-perforated
appendicitis, from 138.5 to 68.4 per 100 000 person-years between 1987 and 2009.
The incidence rate of perforated appendicitis decreased from 28.0 to 19.9 per 100
000 person-years and negative appendicectomies reduced from 48.5 to 3.6 per 100
000 person-years during the study interval. Conclusion: The incidence rates of
acute appendicitis and negative appendicectomy have reduced markedly in Swedish
children over time, with significantly different trends amongst non-perforated
appendicitis and perforated appendicitis. The full explanation for the observed
findings is unclear.
PMID- 29951639
TI - Creation of a universal language for surgical procedures using the step-by-step
framework.
AB - Background: Learning of surgical procedures is traditionally based on a master
apprentice model. Segmenting procedures into steps is commonly used to achieve an
efficient manner of learning. Existing methods of segmenting procedures into
steps, however, are procedure-specific and not standardized, hampering their
application across different specialties and thus worldwide uptake. The aim of
this study was to establish consensus on the step-by-step framework for
standardizing the segmentation of surgical procedures into steps. Methods: An
international expert panel consisting of general, gastrointestinal and
oncological surgeons was approached to establish consensus on the preciseness,
novelty, usefulness and applicability of the proposed step-by-step framework
through a Delphi technique. All statements were rated on a five-point Likert
scale. A statement was accepted when the lower confidence limit was 3.00 or more.
Qualitative comments were requested when a score of 3 or less was given. Results:
In round one, 20 of 49 experts participated. Eighteen of 19 statements were
accepted; the 'novelty' statement needed further exploration (mean 3.05, 95 per
cent c.i. 2.45 to 3.65). Based on the qualitative comments of round one, five
clarifying statements were formulated for more specific statements in round two.
Twenty-two experts participated and accepted all statements. Conclusion: The
international expert panel consisting of general, gastrointestinal and
oncological surgeons supported the preciseness, usefulness and applicability of
the step-by-step framework. This framework creates a universal language by
standardizing the segmentation of surgical procedures into step-by-step
descriptions based on anatomical structures, and may facilitate education,
communication and assessment.
PMID- 29951641
TI - Radiological findings in ancient Egyptian canopic jars: comparing three standard
clinical imaging modalities (x-rays, CT and MRI).
AB - Background: The aim of our study was to evaluate the potential and the
limitations of standard clinical imaging modalities for the examination of
ancient Egyptian canopic jars and the mummified visceral organs (putatively)
contained within them. Methods: A series of four ancient Egyptian canopic jars
was imaged comparing the three standard clinical imaging modalities: x-rays,
computed tomography (CT) and magnetic resonance imaging (MRI). Additionally,
imaging-data-based volumetric calculations were performed for quantitative
assessment of the jar contents. Results: The image contrast of the x-ray images
was limited by the thickness and high density of the calcite mineral constituting
the examined jars. CT scans showed few artefacts and revealed hyperdense
structures of organ-specific morphology, surrounded by a hypodense homogeneous
material. The image quality of MRI scans was limited by the low amount of water
present in the desiccated jar contents. Nevertheless, areas of pronounced signal
intensity coincided well with hyperdense structures previously identified on CT
scans. CT-based volumetric calculations revealed holding capacities of the jars
of 626-1319 cm3 and content volumes of 206-1035 cm3. Conclusions: CT is the
modality of choice for non-invasive examination of ancient Egyptian canopic jars.
However, despite its limitations, x-ray imaging will often remain the only
practicable method for on-site investigations. Overall, the presented
radiological findings are more compatible with contained small organ fragments
rather than entire mummified organs, as originally expected, with consequent
implications for envisioned future sampling for chemical and genetic analysis.
PMID- 29951640
TI - Patient-reported outcomes for patients with metastatic castration-resistant
prostate cancer receiving docetaxel and Atrasentan versus docetaxel and placebo
in a randomized phase III clinical trial (SWOG S0421).
AB - Background: SWOG S0421 was a large randomized trial comparing
docetaxel/prednisone plus placebo (DPP) to docetaxel/prednisone plus atrasentan
over 12 cycles for patients with metastatic castration-resistant prostate cancer
(mCRPC). The current report presents the PRO results for this trial, an important
secondary endpoint. Methods: The trial specified two primary PRO endpoints.
Palliation of worst pain was based on the Brief Pain Inventory (BPI), where a 2
point difference is defined as clinically meaningful. Improvement of functional
status was based on the Functional Assessment of Cancer Therapy - Prostate Cancer
Trial Outcome Index (FACT-P TOI); a 5-point difference has been defined as
clinically meaningful. We compared rates by arm using chi-square tests.
Longitudinal analyses using linear mixed models addressed changes by arm over
time. Results: Four-hundred eighty-nine patients on each arm were evaluable for
PRO endpoint data. There were no differences by arm in clinically meaningful pain
palliation (41.7% for DPP vs. 44.0% for DPA, p = .70) or functional status (24.2%
for DPP vs. 28.7% for DPA, p = .13). Longitudinal comparisons indicated no
differences over time by arm for BPI Worst Pain scores (0.13 points, p = .23).
Patients on the DPA arm had improved functional status of 1.78 points on average,
a statistically significant (p = .02) but not clinically meaningful difference.
Conclusions: The SWOG S0421 PRO data showed little evidence of clinically
meaningful differences by arm in either pain palliation or functional status.
PMID- 29951642
TI - Myocardial blood flow and myocardial flow reserve values in 13N-ammonia
myocardial perfusion PET/CT using a time-efficient protocol in patients without
coronary artery disease.
AB - Background: Cardiac imaging by means of myocardial Positron Emission
Tomography/Computed Tomography (PET/CT) is being used increasingly to assess
coronary artery disease, to guide revascularization decisions with more accuracy,
and it allows robust quantitative analysis of both regional myocardial blood flow
(MBF) and myocardial flow reserve (MFR).Recently, a more time-efficient protocol
has been developed in combination with a residual activity correction algorithm
in which a stress acquisition is performed directly after completion of the rest
acquisition to subtract remaining myocardial radioactivity.The objective of this
study is to define flow values of myocardial blood flow (MBF) and Myocardial Flow
Reserve (MFR) with 13N-ammonia (13NH3) myocardial perfusion PET/CT on patients
without coronary artery disease using a time-efficient protocol, since reference
values for this particular type of study are lacking in literature. In addition,
we aim to determine the effect of the residual activity correction algorithm in
this time-efficient protocol. Results: A mean MBF in rest of 1.02 +/- 0.22
ml/g/min, a mean MBF in stress of 2.54 +/- 0.41 ml/g/min with a mean MFR of 2.60
+/- 0.61 were measured. Female patients had a significant higher MBF in rest and
stress, but lower MFR; a small but significant negative correlation was measured
between age and MBF in stress and MFR. Residual activity correction had a
significant effect resulting in a difference in global stress MBF before and
after correction of 0.39 +/- 0.13 ml/g/min. Conclusions: This study established
flow values for 13NH3 myocardial PET/CT with a time-efficient protocol, and
established that MBF in stress corrected for residual activity is comparable with
known reference values in normal studies without temporal overlap. Further
validation of the technique could be of value, e.g. by comparison to standard
imaging without temporal overlap, or validation against catheterization results.
PMID- 29951643
TI - Aberrant expression of p16INK4a in human cancers - a new biomarker?
AB - The ARF and INK4a genes are located in the same CDKN2a locus, both showing its
tumor suppressive activity. ARF has been shown to detect potentially harmful
oncogenic signals, making incipient cancer cells undergo senescence or apoptosis.
INK4a, on the other hand, responds to signals from aging in a variety of tissues
including islets of Langerhans, neuronal cells, and cancer stem cells in general.
It also detects oncogenic signals from incipient cancer cells to induce them
senescent to prevent neoplastic transformation. Both of these genes are
inactivated by gene deletion, promoter methylation, frame shift, and aberrant
splicing although mutations changing the amino acid sequences affect only the
latter. Recent studies indicated that polycomb gene products EZH2 and BMI1
repressed p16INK4a expression in primary cells, but not in cells deficient for
pRB protein function. It was also reported that that p14ARF inhibits the
stability of the p16INK4a protein in human cancer cell lines and mouse embryonic
fibroblasts through its interaction with regenerating islet-derived protein
3gamma. Overexpression of INK4a is associated with better prognosis of cancer
when it is associated with human papilloma virus infection. However, it has a
worse prognostic value in other tumors since it is an indicator of pRB loss. The
p16INK4a tumor suppressive protein can thus be used as a biomarker to detect
early stage cancer cells as well as advanced tumor cells with pRB inactivation
since it is not expressed in normal cells.
PMID- 29951644
TI - The potential dangers of neck manipulation & risk for dissection and devastating
stroke: An illustrative case & review of the literature.
AB - Chiropractic cervical manipulation is a common practice utilized around the
world. Most patients are never cleared medically for manipulation, which can be
devastating for those few who are at increased risk for dissections. The high
velocity thrust used in cervical manipulation can produce significant strain on
carotid and vertebral vessels. Once a dissection has occurred, the risk of
thrombus formation, ischemic stroke, paralysis, and even death is drastically
increased. In this case report, we highlight a case of a 32-year-old woman who
underwent chiropractic manipulation and had vertebral artery dissection with
subsequent brainstem infarct. She quickly deteriorated and passed away shortly
after arrival to the hospital. Although rare, one in 48 chiropractors have
experienced such an event. We utilize this case to highlight the risk associated
with cervical manipulation and urge open dialogue between chiropractors and
physicians. Receiving medical clearance prior to cervical manipulation in
potential at risk patients would drastically reduce morbidity and mortality.
PMID- 29951645
TI - Hearing Loss Contributes to Balance Difficulties in both Younger and Older
Adults.
AB - Objective: The number of steps required to regain balance is an easily obtainable
clinical outcome measure. This study assessed whether number of steps during loss
of balance could identify older adults with hearing loss who have balance
deficits. We aimed to answer two questions: 1) Does hearing loss negatively
affect the ability to regain balance, as reflected by an increased number of
steps needed to respond to a perturbation while simultaneously attending to
speech-in-noise; and 2) Do hearing aids improve balance control, reflected by a
decrease in number of steps needed to regain balance? Methods: 20 young adults
and 20 older adults with normal hearing, and 19 older adults with hearing loss
performed an auditory-balance dual-task. Participants were asked to listen and
repeat back sentences from a standardized audiology test, while simultaneously
responding to backward surface translations. Outcome measures were performed on
the auditory test and number of steps needed to regain balance. Repeated measures
ANCOVA models were run in using group, time, hearing levels, and perturbation
levels as predictors. Results: Auditory scores confirmed difficulty hearing
speech-in-noise in older adults with hearing loss and no hearing aids, and in
young and older adults with normal hearing and simulated hearing loss. Results
showed that group, auditory and balance conditions are significantly related to
both outcomes measures and time is not significant for steps. Older adults with
hearing loss had a significant increase in number of steps needed to regain
balance compared to young adults and older adults with normal hearing.
Conclusion: Number of steps may be an appropriate clinical assessment tool for
identifying fall risk in older adults with hearing loss. Further research needs
to be performed to identify proper assessments and treatment interventions for
older adults with hearing loss who have balance deficits.
PMID- 29951646
TI - Temporal Lobe Epilepsy, Stroke, and Traumatic Brain Injury: Mechanisms of
Hyperpolarized, Depolarized, and Flow-Through Ion Channels Utilized as Tri
Coordinate Biomarkers of Electrophysiologic Dysfunction.
AB - The brain is an integrated network of multiple variables that when compromised
create a diseased state. The neuropathology of temporal lobe epilepsy (TLE),
stroke, and traumatic brain injury (TBI) demonstrate both similarity and
complexity that reflects this integrated variability; TLE with its live human
tissue resection provides opportunity for translational science to demonstrate
scale equivalent experimentation between the macroscopic world of clinical
disease and the microscopic world of basic science. The extended value of this
research is that the neuroinflammatory abnormalities that occur throughout
astrocytes with hippocampal sclerosis and damaged or even reversed signaling
pathways (inhibition to excitation such as with gaba-aminobutyric acid) are
similar to those seen in post-stroke and TBI models. In evaluation of the
epilepsy population this interconnectedness of pathology warrants further
evaluation with collaborative efforts. This review summarizes patterns that could
shift experimentation closer to the macro level of humanity, but still represent
the micro world of genetics, epigenetics, and neuro-injury across etiologies of
physiologic dysfunction such as TLE, stroke, and TBI with evaluation of cell
function using electrophysiology. In conclusion we demonstrate the plausibility
of electrophysiologic voltage and current measurement of brain tissue by patch
clamp analysis to specify actual electrophysiologic function for comparison to
electroencephalography in order to aid neurologic evaluation. Finally, we discuss
the opportunity with multiscale modeling to display integration of the
hyperpolarization cyclic-nucleotide gated channel, the depolarized calcium
channels, and sodium-potassium-chloride-one/potassium-chloride-two co-transporter
channels as potential mechanisms utilized as tri-coordinate biomarkers with these
three forms of neurologic disease at a molecular scale of electrophysiologic
pathology.
PMID- 29951648
TI - Visible-light induced three-component alkynyl-difluoroalkylation of unactivated
alkenes.
AB - A visible-light induced three-component reaction of difluoroalkyl halides,
unactivated alkenes, and alkynyl sulfones is described, providing a direct and
general approach to the construction of synthetically valuable beta
difluoroalkylated alkynes under room temperature conditions. This represents the
first intermolecular alkynyl-difluoroalkylation of unactivated alkenes.
PMID- 29951647
TI - Near-infrared incoherent broadband cavity enhanced absorption spectroscopy (NIR
IBBCEAS) for detection and quantification of natural gas components.
AB - The principle of near-infrared incoherent broadband cavity enhanced absorption
spectroscopy was employed to develop a novel instrument for detecting natural gas
leaks as well as for testing the quality of natural gas mixtures. The instrument
utilizes the absorption features of methane, butane, ethane, and propane in the
wavelength region of 1100 nm to 1250 nm. The absorption cross-section spectrum in
this region for methane was adopted from the HITRAN database, and those for the
other three gases were measured in the laboratory. A singular-value decomposition
(SVD) based analysis scheme was employed for quantifying methane, butane, ethane,
and propane by performing a linear least-square fit. The developed instrument
achieved a detection limit of 460 ppm, 141 ppm, 175 ppm and 173 ppm for methane,
butane, ethane, and propane, respectively, with a measurement time of 1 second
and a cavity length of 0.59 m. These detection limits are less than 1% of the
Lower Explosive Limit (LEL) for each gas. The sensitivity can be further enhanced
by changing the experimental parameters (such as cavity length, lamp power etc.)
and using longer averaging intervals. The detection system is a low-cost and
portable instrument suitable for performing field monitorings. The results
obtained on the gas mixture emphasize the instrument's potential for deployment
at industrial facilities dealing with natural gas, where potential leaks pose a
threat to public safety.
PMID- 29951649
TI - Thermosensitive molecularly imprinted core-shell CdTe quantum dots as a
ratiometric fluorescence nanosensor for phycocyanin recognition and detection in
seawater.
AB - Versatile molecular imprinted fluorescence sensors have been prepared for various
species, but the imprinting based fluorescence detection of target proteins upon
different external stimulation is rarely reported. Herein, a novel phycocyanin
imprinted ratiometric fluorescence nanosensor was developed for the temperature
regulated sensing and detection of a phycocyanin target based on fluorescence
resonance energy transfer (FRET). The nanosensor was fabricated via simple facile
copolymerization, with amino/carboxyl modified quantum dots (QDs) as a
fluorescent support, N-isopropylacrylamide as a thermo-responsive functional
monomer, N,N-methylenebisacrylamide as a cross-linker and phycocyanin as a
template. Under temperature control at 20 degrees C and 45 degrees C, the
fluorescence intensities of the QDs and phycocyanin were regularly decreased and
enhanced, respectively, to a different extent as the concentration of phycocyanin
increased, and thereby the ratio of the two fluorescence peak emission
intensities of QDs and phycocyanin was used to determine the concentration of
phycocyanin. Good linearity was obtained within the range of 0-1.8 MUM (r =
0.9900) with a low detection limit of 3.2 nM, and excellent recognition
selectivity towards the phycocyanin target was achieved over other proteins.
Moreover, satisfactory recoveries of 92.0-106.8% were obtained in spiked seawater
samples. This study provides a facile, fast and intelligent way to conduct
identification analysis of trace proteins in complex water matrices, and can push
forward protein imprinting and stimuli-responsive imprinting related research.
PMID- 29951650
TI - Substituent effects in pyridyl-functionalized pyrylium salts, pyridines and
lambda3,sigma2-phosphinines: a fundamental and systematic study.
AB - A series of substituted, pyridyl-functionalized 2,4,6-triarylpyrylium salts were
prepared and investigated for their light absorption and emission properties.
After reaction with P(SiMe3)3, the corresponding lambda3-phosphinines were
obtained, which carry on the 4- or 6-aryl ring +/-I and +/-M substituents.
Supported by DFT calculations, a systematic evaluation of the sigma-donor and pi
donor as well as pi-acceptor properties of these low-coordinate P,N-hybrid
ligands was performed. The modular synthetic approach allowed us at the same time
to synthesize the structurally related bipyridine derivatives for comparison
reasons. Reaction of the chelating ligands with [W(CO)6] in THF afforded the
corresponding [(P^N)W(CO)4] and [(N^N)W(CO)4] complexes. A crystallographic
characterization of selected coordination compounds revealed significant
structural differences between the pyridyl-phosphinine- and the bipyridine-based
compounds. Their characterization by means of IR-spectroscopy gave experimental
insight into the electronic properties of the respective ligands.
PMID- 29951652
TI - Different angiogenesis modes and endothelial responses in implanted porous
biomaterials.
AB - An in vivo experimental model based on implanting porous biomaterials to study
angiogenesis was proposed. In the implanted porous polyvinyl alcohol, three major
modes of angiogenesis, sprouting, intussusception and splitting, were found. By
electron microscopy and three-dimensional simulation of the angiogenic vessels,
we investigated the morphological characteristics of the three modes and paid
special attention to the initial morphological difference between intussusception
and splitting, and it was confirmed that the endothelial abluminal invagination
and intraluminal protrusion are pre-representations of intussusception and
splitting, respectively. Based on immunohistochemical analysis of HIF-1alpha,
VEGF and Flt-1 expressions, it was demonstrated that the dominant mode of
angiogenesis is related to the local hypoxic condition, and that there is
difference in the response of endothelial cells to hypoxia-induced VEGF between
sprouting and splitting. Specifically, in the biomaterials implanted for 3 days,
the higher expression and gradient of VEGF induced by severe hypoxia in the
avascular area caused sprouting of the peripheral capillaries, and in the
biomaterial implanted for 9 days, with moderate hypoxia, splitting became a
dominant mode. Whether on day 3 or day 9, Flt-1 expression in sprouting
endothelia was significantly higher than that in splitting endothelia, which
indicates that sprouting is caused by the strong response of endothelial cells to
VEGF, while splitting is associated with their weaker response. As a typical
experimental example, these results show the effectiveness of the porous
biomaterial implantation model for studying angiogenesis, which is expected to
become a new general model.
PMID- 29951651
TI - The short-term supplementation of monacolin K improves the lipid and metabolic
patterns of hypertensive and hypercholesterolemic subjects at low cardiovascular
risk.
AB - Background - The clinical hypocholesterolemic effect of nutraceutical compounds
(NCs) containing red yeast rice extracts providing a daily dose of 2.5-10 mg of
monacolin K is now well established. For this reason, NCs may be a viable
alternative to the statin drugs commonly used to lower cholesterol levels.
However, in order to avoid some possible statin-like side effects, most NCs
available on the market contain low doses of monacolin K, which could reduce
their efficacy. The aim of this study was to investigate the efficacy and safety
of a NC containing high doses of monacolin K (10 mg) in improving the lipid
profile and glucose metabolism when added to the diet versus the diet alone in a
group of hypertensive and hyper-cholesterolemic subjects at low cardiovascular
risk. Methods - Thirty subjects with grade-1 essential hypertension (mean age
51.5 +/- 7.8 years, 62.9% males) were enrolled in the treatment group (NC group).
These subjects followed a programmed diet and took one tablet a day of a NC
containing red yeast rice, policosanols, resveratrol and chromium picolinate for
1 month and were compared with an equivalent group of subjects that followed only
a diet program. Differences in serum total cholesterol (TC), low-density- and
high-density-lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG) and
blood glucose between groups were compared by analysis of variance. Results - In
both groups, a significant reduction of TC, TG and LDLC was observed. In the
treatment group from the baseline to the follow-up the reduction of TC (230.93 +/
28.0 vs. 188.63 +/- 18.1, p < 0.001) and LDLC (153.10 +/- 22.5 vs. 116.54 +/-
17.7, p < 0.001) was significantly greater compared to the control group
(differences between treatments = 9.19% and 12.29%, respectively); in addition a
significant higher reduction in blood glucose (89.1 +/- 7.6 vs. 83.7 +/- 4.6, p <
0.001) was also observed (differences between treatments = 4.28%). HDLC levels
remained unchanged in both groups. Conclusions - In summary, the NC containing
high doses of monacolin K appeared to be safe, well tolerated and effective at
improving lipid and glucose patterns.
PMID- 29951653
TI - Asymmetric total synthesis of naturally occurring spirocyclic
tetranorsesquiterpenoid lanceolactone A.
AB - Asymmetric total synthesis of naturally occurring gamma-butenolide containing
[4.4]spiro-tetrahydrofuran lanceolactone A has been reported in the present work.
Bimetallic ("Pd-Cu") cascade cyclization was the crucial reaction employed for
the construction of the gamma-butenolide framework of the natural product.
Subsequently, iodocyclization and reductive deiodination through a transfer
hydrogenation reaction were applied to access the target molecule in an efficient
manner.
PMID- 29951654
TI - Dynamic layer-by-layer films on nanofiber membrane: a platform for ultra
sensitive bacterial concentration detection.
AB - Herein, a new platform was established for ultra-sensitive bacterial
concentration detection. The sensing system had a linear relationship with the
logarithm of bacterial concentration from 1 * 101 to 1 * 105 CFU mL-1 within 5
min. Moreover, the platform showed excellent consistency compared with the
traditional standard method against practical samples.
PMID- 29951656
TI - Molecular vibration as a novel explanatory mechanism for the expression of animal
colouration.
AB - Animal colouration is characterized by the concentration of pigments in
integumentary structures and by the nanoscale arrangement of constitutive
elements. However, the influence of molecular vibration on colour expression has
been overlooked in biology. Molecular vibration occurs in the infrared spectral
region, but vibrational and electronic properties can influence each other. Thus,
the vibration of pigment molecules may also affect their absorption properties
and the resulting colours. We calculated for the first time the relative
contribution of molecular vibration (by means of Raman spectroscopy) and
concentration (by means of HPLC) of melanin polymers, the most common animal
pigments, to generate diversity in plumage colour in 47 species of birds.
Vibrational characteristics explained >9 times more variance in colour expression
than the concentration of melanins. Additionally, we modelled melanin Raman
spectra on the basis of the chemical structure of their constituent monomers and
calculated the Huang-Rhys factors for each vibrational mode, which indicate the
contribution of these modes to the electronic spectra responsible for the
resulting colours. High Huang-Rhys factors frequently coincided with the
vibrational modes of melanin monomers. Our results can be explained by the
influence of molecular vibration on the absorption properties of melanins. The
colour of organisms may thus mainly result from the vibrational properties of
their molecules and only residually from their concentration. As a given melanin
concentration can give rise to different colours because different structural
melanin conformations can present different vibrational characteristics,
vibrational effects may favour phenotypic plasticity and thus constitute an
important evolutionary force.
PMID- 29951655
TI - A ruthenium-platinum metal complex that binds to sarcin ricin loop RNA and lowers
mRNA expression.
AB - IT127 is a dinuclear transition metal complex that contains a Pt(ii) and a
Ru(iii) metal center. We have shown that IT127 is significantly more effective in
binding the 29-base sarcin ricin loop (SRL) RNA in comparison to Cisplatin, a
hallmark anticancer agent. Binding site analysis shows that IT127 prefers purine
bases and the GAGA tetraloop region of SRL RNA. Our results with a dihydrofolate
reductase (DHFR) model system reveal that IT127 binding to mRNA reduces
translation of DHFR enzyme and that the Ru(iii) and Pt(ii) centers in IT127
appear to work in a synergistic manner.
PMID- 29951657
TI - Substrate-controlled divergent synthesis of polycyclic indoloazepines and
indolodiazepines via 1,5-hydride shift/7-cyclization cascades.
AB - Novel and practical acid-catalyzed cyclization of 2-indolyl aryl carbinols via
tandem dehydration/1,5-hydride shift/7-cyclization sequences has been developed.
By appropriate variation of the substrate, diverse polycyclic-fused indoles were
synthesized in good yield, thus demonstrating the high efficiency, transition
metal-free nature, and high step/atom economy of the synthesis strategy.
PMID- 29951658
TI - Versatile coordination of acetazolamide to ruthenium(ii) p-cymene complexes and
preliminary cytotoxicity studies.
AB - The carbonic anhydrase inhibitor acetazolamide (AcmH2) reacted with [(eta6-p
cymene)RuCl(MU-Cl)]2 to afford [(eta6-p-cymene)RuCl2(kappaN-AcmH2)], 1A, in near
quantitative yield. In methanol, 1A exists in equilibrium with 1B, being probably
a coordination isomer, as established by VT 1H-EXSY NMR spectroscopy. DFT
calculations pointed to a higher stability of 1A with respect to 1B. [(eta6-p
cymene)RuCl(kappa2N,N'-AcmH)], 2, was obtained in 86% yield from [(eta6-p
cymene)RuCl(MU-Cl)]2 and AcmH2 in the presence of NaOH. The reactions of 2 with
AgNO3 (in water), pta/AgNO3 or pta/AgOTf/Et3N (in methanol) afforded the nitrate
coordinated complex [(eta6-p-cymene)Ru(kappaO-NO3)(kappa2N,N'-AcmH)], 3, the salt
[(eta6-p-cymene)Ru(kappa2N,N'-AcmH)(kappaP-pta)]NO3, [4]NO3, and the zwitterion
[(eta6-p-cymene)Ru(kappa2N,N'-Acm)(kappaP-pta)], 5, respectively, in high yields
(pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane). The reactions of 5 with
Bronsted acids yielded the protonated-pta species [(eta6-p-cymene)Ru(kappa2N,N'
Acm)(kappaP-ptaH)]X [6]X (X = NO3, TsO). All compounds were fully characterized
by analytical and spectroscopic methods, and the structures of 1A, 2 and 5 were
elucidated by X-ray diffraction. The stability of the compounds was investigated
in aqueous media and 2 and 5 were evaluated for their cytotoxicity towards human
ovarian A2780 and A2780cisR cancer cells and non-tumorigenic HEK-293 cells.
PMID- 29951659
TI - Phosphorescence emission and fine structures observed respectively under ambient
conditions and at ca. 55 K in a coordination polymer of lead(ii)
thiophenedicarboxylate.
AB - Under solvothermal conditions, a robust Pb2+-based coordination polymer (CP),
[Pb(TDC)]n (1), where H2TDC is thiophenedicarboxylic acid, has been achieved.
Structural analysis reveals that 1 crystallizes in the monoclinic space group
C2/c, where the Pb2+ ions show quadrangular prism coordination geometry. CP 1
represents a 3D coordination network based on a TDC2- ligand as bridges and
quadrangular prismatic PbO8 units as nodes, among which the PbO8 units are
extended through edge-sharing to form a 2D layer in the bc plane. Interestingly,
CP 1 emitted intense and long-lived orange phosphorescence in the solid state at
room temperature, with a quantum yield of 6.7% and a phosphorescence lifetime of
1.78 ms. A fine structure is clearly observed in the phosphorescence emission
spectra at temperatures below 55 K. The emission mainly arose from the electron
transition within the pi-type orbitals of the TDC2- ligand. This study gives a
fresh impetus to achieve CP-based long-lived phosphorescent materials under
ambient conditions.
PMID- 29951660
TI - A Co(ii) framework derived from a tris(4-(triazol-1-yl)phenyl)amine redox-active
linker: an electrochemical and magnetic study.
AB - A new 3D coordination polymer {[Co2(MU-OH2)(TTPA)(DTDN)2.DMF].H2O}n (1, TTPA =
tris(4-(1H-1,2,4-triazol-1-yl)phenyl)amine, DTDN = 6,6'-dithiodinicotinate) was
synthesised and characterised. The redox properties of this framework were
elucidated by solid state electrochemical and spectroelectrochemical data. This
is the first investigation of the redox behaviour of TTPA in coordination
polymers. Furthermore, the incorporation of a paramagnetic Co(ii) metal ion into
the framework caused 1 to show spin-flop behaviour as the result of a field
induced magnetic transition. The incorporation of two flexible ligands and Co(ii)
metal ions represents a feasible approach for the advancement of multifunctional
materials.
PMID- 29951661
TI - Fusing triphenylphosphine with tetraphenylborate: introducing the 9
phosphatriptycene-10-phenylborate (PTB) anion.
AB - In a fusion of two ubiquitous organometallic reagents, triphenylphosphine (PPh3)
and tetraphenylborate (BPh4-), the 9-phosphatriptycene-10-phenylborate (PTB)
anion has been prepared for the first time. This borato species has been fully
characterized by a suite of spectroscopic methods, and initial reactivity studies
introduce it as a competent ligand for transition metals, including Co(ii) and
Fe(ii).
PMID- 29951662
TI - First-principles studies of polar perovskite KTaO3 surfaces: structural
reconstruction, charge compensation, and stability diagram.
AB - Polar perovskite oxides are of considerable interest for developing advanced
functional materials with exceptional electronic properties for their unique
polar characters. A cleavage of polar perovskite oxides along the charged layers
leads to an electrostatic instability on the cleaved surfaces, and a charge
compensation is required to stabilize these surfaces. In this work, we have
systemically studied 25 types of surface models of polar KTaO3 perovskite oxide,
including (001), (110), and (111) surfaces with various types of surface
terminations, using first-principles electronic structure calculations. The
surface structural reconstruction, electronic structures, and thermodynamic
properties including cleavage energy and surface energy are investigated. The
phase stability diagrams of the (001), (110), and (111) surfaces are constructed
with respect to the chemical potentials of component elements. The KO(001),
O(110), and KO2(111) terminations are more likely to be formed than other types
of terminations in corresponding surfaces, consistent with experimental
observations on KTaO3(001) surfaces. This work provides useful guidance for
accurate control of surface morphology for tailing functional properties of polar
KTaO3 perovskite oxide.
PMID- 29951663
TI - A fluorescent layered oxalato-based canted antiferromagnet.
AB - We report the synthesis and characterization of the first fluorescent oxalato
based canted antiferromagnet. Compound [DOC][MnFe(C2O4)3] (1) (DOC = 3,3'
diethyloxacarbocyanine) combines the well-known canted antiferromagnetic
[MnFe(C2O4)3]- honeycomb layers with a fluorescent cationic cyanine-type
fluorescent dye. Besides the expected spin canted antiferromagnetic order in the
oxalato layer at ca. 29 K, we show the key role played by the anionic oxalato
lattice in the optical properties of the cation since it provides isolation of
dye cations in the hexagonal cavities of the oxalato-based matrix. The emission
of the DOC+ dye shows a redshift and a broadening of the emission as well as an
increase in the lifetime compared to the emission of the DOC+ cations in
solution. These facts are attributed to the isolation effect of the oxalato-based
matrix.
PMID- 29951669
TI - Metal bis(acetylide) complex molecular wires: concepts and design strategies.
AB - The past decade has seen a remarkable surge in studies of thin-film and single
molecule electronics, due in no small part to the development and advancement of
experimental methods for the construction and measurement of metal|molecule|metal
junctions. Within the plethora of molecular structures that have been
investigated, metal complexes of general form trans-M(C[triple bond, length as m
dash]CR)2(Ln) have attracted attention from the inorganic and organometallic
chemistry community in the search for efficient molecular wires due to the
potential pi-d-pi orbital mixing along the molecular backbone. In this article
progress towards this goal will be summarised, and design strategies for future
molecular components discussed.
PMID- 29951670
TI - On the structure of superbasic (MgO)n sites solvated in a faujasite zeolite.
AB - We report the synthesis and characterisation of a HY/MgO zeolite/oxide
nanocomposite material with high crystallinity and highly dispersed, highly basic
MgO sites. Preparation was optimized in order to preserve sample crystallinity,
to avoid the formation of mesoporosity and to minimize the formation of separate
Mg-containing phases. These features were checked by means of electron
microscopy, X-ray powder diffraction, porosimetry and IR spectroscopy. A highly
dispersed material was obtained, comprising nanoclusters of magnesium oxide and
hydroxide hosted by the microporous zeolite framework. The location and structure
of the Mg-containing clusters have been studied by means of a combination of
Rietveld refinement of XRPD data and high quality quantum mechanical simulations.
The refinement has shown the presence of magnesium and oxygen atoms in the double
six-membered ring cages, consistent with the presence of mononuclear Mg moieties.
However, the composition and IR spectroscopy demonstrate that other Mg species
must exist, likely located in the zeolite pores. In order to propose candidate
structures for these species, several hypothetic periodic models of the material
were built by placing (MgO)n clusters in different locations of the zeolite
structure, taking into account the material composition and other constraints
imposed by the experimental observations. Periodic structures with P1 symmetry
were optimized at the B3LYP-D*/DZVP level with the CRYSTAL code and classified
according to their stability. Two families of possible sites were identified:
highly solvated (MgO)n units in narrow cavities and less coordinated clusters in
the supercages. The stability of these clusters appears to be regulated by the
ability of Mg2+ and O2- ions to interact with the pore walls and by the formation
of Mg-OH species as result of the reaction of Mg-O couples with remaining acidic
protons. The reactivity of four representative models with CO2 has been simulated
at the B3LYP-D*/TZVP level. CO2 forms very stable linear end-on adducts with low
coordinated Mg ions in most cases. Isolated sites give rise to bridge bidentate
complexes in agreement with previous spectroscopic observations. The formation of
hydrogen-carbonates is observed only on specific sites, through a process having
a low adsorption energy because of the high deformation of the adsorption site.
PMID- 29951671
TI - Hyper-cross-linked polymers with controlled multiscale porosity via
polymerization-induced microphase separation within high internal phase emulsion.
AB - We report the preparation of hierarchically porous polymers containing fully
interconnected and controlled micro-, meso-, and macropores, where a hyper-cross
linked microporous polymer skeleton forms a reticulating mesoporous wall that
supports a highly porous macropore framework. These materials provide high
specific surface area and >90% porosity, useful for rapid sorption of organic
molecules.
PMID- 29951672
TI - Colloidal systems of surface active ionic liquids and sodium carboxymethyl
cellulose: physicochemical investigations and preparation of magnetic nano
composites.
AB - The complexation of three surface active ionic liquids (SAILs): 1-methyl-3
dodecylimidazolium chloride, [C12mim][Cl], and its amide, 3-(2-(dodecylamino)-2
oxoethyl)-1-methyl-1H-imidazol-3-ium chloride, [C12Amim][Cl], and ester, 3-methyl
1-dodecyloxycarbonylmethylimidazolium chloride, [C12Emim][Cl], functionalized
counterparts with sodium carboxymethylcellulose (NaCMC), has been investigated.
The behaviour of colloidal systems comprising SAILs and NaCMC at the air-solution
interface has been investigated using tensiometry. The formed colloids in the
bulk have been characterized for their mobility, surface charge, shape, size and
morphology along with their relative hydrophobicity/hydrophilicity and other
thermodynamic parameters of interest in different concentration regimes of the
SAILs. For this, various techniques such as conductivity, turbidity, dynamic
light scattering, zeta-potential, scanning electron microscopy (SEM) and
fluorescence measurements have been employed. H-bonding prone SAILs, i.e.
[C12Amim][Cl] and [C12Emim][Cl], are found to interact with NaCMC in a
contrasting manner as compared to their non-functionalized counterpart. The
formed complexes of SAILs and NaCMC have been explored for the one pot
preparation of magnetic nano-composites by doping colloids of SAILs and NaCMC
with zinc ferrite (ZnFe3O4) nano-particles. The prepared magnetic nano-composites
are characterised using X-ray diffraction (XRD), transmission electron microscopy
(TEM) and vibrating sample magnetometry (VSM). It is expected that the present
work would offer a new colloidal route for the preparation of SAILs and
biopolymer assisted nano-composites along with providing physical insights into
the complexation phenomenon.
PMID- 29951673
TI - Electrochemical water oxidation using a copper complex.
AB - Herein, we report the application of the mononuclear copper complex 1,
[CuII(L)]2+, in electrochemical water oxidation catalysis (L = 1,3-bis(((1-methyl
1H-imidazol-2-yl)methyl)amino)propan-2-ol). The complex exhibits a N4 donor set
consisting of two amine and two imidazole units and a dangling OH unit in close
proximity to the copper ion. 1 exhibits a moderate apparent rate constant kcat of
0.12 s-1 in catalysis and operates at an overpotential of 0.83 V. Detailed
investigations allowed us to derive a mechanism for water oxidation. The
catalysis proceeds only under basic conditions, where [CuII(L)(OH)]+, 1H-1, is
the main solution species, which indicates that a negatively charged ligand is
necessary to drive the catalysis. Initial oxidation of 1H-1 is coupled to proton
loss forming a copper(iii) species and further oxidation initiates oxygen
evolution. Initial oxidation of 1 under neutral, i.e. non-catalytic, conditions
is pH independent, highlighting the importance of PCET steps during catalysis. We
collected reasonable evidence that catalysis proceeds via a water nucleophilic
attack mechanism. The electrolyte presumably acts as a proton acceptor in
catalysis as the onset potential depends on the buffer employed.
PMID- 29951674
TI - Effects of diminished steric protection at phosphorus on stability and reactivity
of oxaphosphirane complexes.
AB - Readily available P-tBu substituted Li/Cl phosphinidenoid complexes react with
carbonyl compounds to furnish sterically almost unhindered oxaphosphirane
complexes that reveal new and surprisingly facile intra- and intermolecular ring
expansion reactions. 1,3,2-Dioxaphosphole complex formation is explained by DFT
calculations through diastereoselective carbonyl group-induced ring cleavage of
an oxaphosphirane intermediate.
PMID- 29951675
TI - Droplet-train induced spatiotemporal swelling regimes in elastomers.
AB - In this work, we perform a combined experimental and numerical analysis of
elastomer swelling dynamics upon impingement of a train of solvent droplets. We
use time scale analysis to identify spatiotemporal regimes resulting in distinct
boundary conditions that occur based on relative values of the absorption
timescale and the droplet train period. We recognize that when either timescale
is significantly larger than the other, two cases of quasi-uniform swelling
occur. In contrast, when the two timescales are comparable, a variety of
temporary geometrical features due to localized swelling are observed. We show
that the swelling feature and its temporal evolution depends upon geometric
scaling of polymer thickness and width relative to the droplet size. Based on
this scaling, we identify six cases of localized swelling and experimentally
demonstrate the swelling features for two cases representing limits of thickness
and width. A finite element model of local swelling is developed and validated
with experimental results for these two cases. The model is subsequently used to
explore the swelling behavior in the rest of the identified cases. We show that
depending upon the lateral dimension of the sample, swelling can locally exhibit
mushroom, mesa, and cap like shapes. These deformations are magnified during the
droplet-train impact but dissipate during post-train polymer equilibration. Our
results also show that while swelling shape is a function of lateral dimensions
of the sample, the extent of swelling increases with the elastomer sample
thickness.
PMID- 29951676
TI - Raman imaging of heme metabolism in situ in macrophages and Kupffer cells.
AB - Herein, we provide the Raman imaging results for different stages of
erythrophagocytosis of senescent red blood cells executed by isolated murine
primary Kupffer cells and a murine macrophage cell line (RAW 264.7). Images were
recorded with the use of 488 and 532 nm excitation lines. The use of Resonance
Raman spectroscopy allowed the visualization of the heme metabolism and tracking
of the systemic iron recycling process inside isolated murine Kupffer cells and
RAW.264 cells. Because of the application of the different experimental assays,
the erythrophagocytosis in two types of cells was presented and associated with
the presence of different forms of oxidized and degradative derivatives of
hemoglobin species. Moreover, we observed an increase of lipid level and later
formation of lipid droplets during the erythrophagocytosis process inside RAW
264.7 macrophages and murine Kupffer cells.
PMID- 29951677
TI - Rationalizing the sign and magnitude of the magnetic coupling and anisotropy in
dinuclear manganese(iii) complexes.
AB - We have synthesised twelve manganese(iii) dinuclear complexes, 1-12, in order to
understand the origin of magnetic exchange (J) between the metal centres and the
magnetic anisotropy (D) of each metal ion using a combined experimental and
theoretical approach. All twelve complexes contain the same bridging ligand
environment of one MU-oxo and two MU-carboxylato, that helped us to probe how the
structural parameters, such as bond distance, bond angle and especially Jahn
Teller dihedral angle affect the magnetic behaviour. Among the twelve complexes,
we found ferromagnetic coupling for five and antiferromagnetic coupling for
seven. DFT computed the J and ab initio methods computed the D parameter, and are
in general agreement with the experimentally determined values. The dihedral
angle between the two Jahn-Teller axes of the constituent MnIII ions are found to
play a key role in determining the sign of the magnetic coupling. Magneto
structural correlations are developed by varying the Mn-O distance and the Mn-O
Mn angle to understand how the magnetic coupling changes upon these structural
changes. Among the developed correlations, the Mn-O distance is found to be the
most sensitive parameter that switches the sign of the magnetic coupling from
negative to positive. The single-ion zero-field splitting of the MnIII centres is
found to be negative for complexes 1-11 and positive for complex 12. However, the
zero-field splitting of the S = 4 state for the ferromagnetic coupled dimers is
found to be positive, revealing a significant contribution from the exchange
anisotropy - a parameter which has long been ignored as being too small to be
effective.
PMID- 29951678
TI - Proteomic responses of carotenoid and retinol administration to Mongolian
gerbils.
AB - Various health benefits of carotenoids have been described. However, while human
observational studies generally suggest positive health effects, supplementation
with relatively high doses of individual carotenoids (supplements) have partly
produced adverse effects. In the present study, we investigated the effect of
several carotenoids on the proteomic response of male Mongolian gerbils (aged 6
weeks). Five groups of gerbils (n = 6 per group) received either retinol (vitamin
A/53 mg per kg bw), all-trans beta-carotene (pro-vitamin A/100 mg kg-1), the non
pro vitamin A carotenoid lutein (100 mg kg-1), the acyclic carotenoid lycopene
(100 mg kg-1) or vehicle (Cremophor EL), via oral single gavage. Gerbils were 12
h post-prandially sacrificed and blood plasma, liver, and white adipose tissue
were collected. For liver and adipose tissue, a 2D-DIGE (difference gel
electrophoresis) approach was conducted; for plasma, proteomic analyses were
achieved by liquid chromatography-mass spectrometry. Compared to controls
(vehicle), various proteins were showing significant abundance variations in
plasma (66), liver (29) and adipose tissue (19), especially regarding structure
(22), protein metabolism (15) and immune system/inflammation (19) functions,
while proteins related to antioxidant effects were generally less abundant,
suggesting no in vivo relevance. Surprisingly, a large overlap in protein
regulation was found between lycopene and retinol exposure, while other
carotenoids, including all-trans beta-carotene, did not show this overlap. Mainly
retinoid acid receptor co-regulated proteins may mechanistically explain this
overlapping regulation. This overlapping regulation may be related to common
nuclear hormone receptor mediated signalling, though further studies using
synthetic ligands of retinoid receptors targeting protein regulation are needed
for confirmation.
PMID- 29951679
TI - Kinetic barriers to alpha-synuclein protofilament formation and conversion into
mature fibrils.
AB - Oligomeric and protofibrillar aggregates that are populated along the pathway of
amyloid fibril formation appear generally to be more toxic than the mature
fibrillar state. In particular, alpha-synuclein, the protein associated with
Parkinson's disease, forms kinetically trapped protofibrils in the presence of
lipid vesicles. Here, we show that lipid-induced alpha-synuclein protofibrils can
convert rapidly to mature fibrils at higher temperatures. Furthermore, we find
that beta-synuclein, generally considered less aggregation prone than alpha
synuclein, forms protofibrils at higher temperatures. These findings highlight
the importance of energy barriers in controlling the de novo formation and
conversion of amyloid fibrils.
PMID- 29951680
TI - Easily reduced bis-pincer (NS2)2molybdenum(iv) to (NHS2)2Mo(ii) by alcohols vs.
redox-inert (NS2)(NHS2)iron(iii) complexes.
AB - Iron and molybdenum complexes supported by a pincer-type dianionic [NS2]2- donor
were prepared to compare their structural, spectroscopic, and electrochemical
properties. The versatility of the [NS2]2Mo(iv) complex (2) to access different
oxidation states was evidenced in the activation of methanol and isopropanol,
oxidising them to formaldehyde or acetone with concomitant reduction and
protonation to afford [NHS2]2Mo(ii), complex (3). This redox behaviour contrasts
with the null reactivity observed for the analogous ferric complex
[NS2][NHS2]Fe(iii) (1). Complex 2 presents a quasi-reversible process at E1/2 =
0.80 V relative to the ferrocenium/ferrocene couple (Fc+/Fc), which is attributed
to the Mo(iv)/Mo(v) redox couple. Two irreversible cathodic processes were
observed at Ecp = -1.59 and -2.20 V, which are attributed to the Mo(iv)/Mo(iii)
and Mo(iii)/Mo(ii) redox couples. Cyclic voltammetry and solid-state structures
obtained by X-ray crystallography support a 2H+ and 2e- process, whereby the
Mo(iv) centre in 2 is reduced sequentially to Mo(iii), and finally to Mo(ii) in
3. These redox events were observed at Ecp = -1.22 and -2.15 V (vs. Fc+/Fc) in
the anodic cyclic voltammograms of 2 in THF in the presence of acid. A new
reduction peak was detected under these conditions at Ecp = -2.30 V, consistent
with electrocatalytic proton reduction. This was corroborated for 2 as a catalyst
precursor in the presence of increasing amounts of p-toluenesulfonic acid, with
the addition of 2 to 14 equivs resulting in an increase of the current measured.
PMID- 29951681
TI - A red-emitting fluorescent probe for the detection of Hg2+ in aqueous medium,
living cells and organisms with a large Stokes shift.
AB - A red-emitting fluorescent probe has been developed for the selective and
sensitive detection of Hg2+. With the addition of Hg2+, the solution of probe 1
displayed a remarkable fluorescence enhancement (102 fold) with lambdaemmax = 625
nm and a large Stokes shift (150 nm). The detection limit of this probe was as
low as 7.1 nM based on S/N = 3. This probe exhibited a good performance in
detecting Hg2+ in real water samples, living cells and organisms.
PMID- 29951682
TI - Mixed azido/phenoxido bridged trinuclear Cu(ii) complexes of Mannich bases:
Synthesis, structures, magnetic properties and catalytic oxidase activities.
AB - Three similar Mannich base ligands viz. N,N-bis(3,5-dimethyl-2-hydroxybenzyl)
N',N'-dimethyl-1,3-diaminopropane (H2L1), N,N-bis(3,5-dimethyl-2-hydroxybenzyl)
N',N'-dimethyl-1,2-diaminoethane (H2L2) and N,N-bis(3,5-dimethyl-2-hydroxybenzyl)
N',N'-diethyl-1,2-diaminoethane (H2L3) upon reaction with Cu(CH3COO)2.H2O
produced dinuclear complexes [Cu2L21-3]. The reaction of each of these isolated
dimeric species with Cu(ClO4)2.6H2O and NaN3 resulted in three new trinuclear
complexes, [(CuL1)2(MU1,1-N3)2Cu(H2O)].CH3OH (1), [(CuL2)2(MU1,1
N3)2Cu(H2O)].CH3OH (2) and [(CuL3)2(MU1,1-N3)2Cu(H2O)].2CH3OH (3), respectively.
The complexes (1-3) have been characterized by elemental analysis and single
crystal X-ray diffraction. In all three complexes, the central Cu(ii) ion is
coordinated by two terminal [CuL] units through a phenoxido and an azido bridge.
These are the first trinuclear Cu(ii) complexes of this type of Mannich base
ligands. Magnetic susceptibility measurements showed intramolecular
antiferromagnetic interactions with J = -64.42, -9.60 and -4.54 cm-1 for 1, 2 and
3, respectively. All three complexes exhibited catecholase-like and phenoxazinone
synthase-like activities towards the aerobic oxidation of 3,5-di-tert
butylcatechol and o-aminophenol, respectively. The turnover numbers (kcat) for
the aerobic oxidation of 3,5-di-tert-butylcatechol are 568.8, 542.1 and 500.4 h-1
and those of o-aminophenol are 125.83, 118.9 and 114.7 h-1 for complexes 1-3,
respectively. The X-band EPR spectroscopy and estimation of the produced hydrogen
peroxide indicated that the aerobic oxidation of 3,5-di-tert-butylcatechol
proceeded through the formation of a semiquinonate radical. The mechanism of
phenoxazinone synthase-like activities is also proposed for trinuclear Cu(ii)
catalysts with the help of mass spectral analysis.
PMID- 29951683
TI - White perovskite based lighting devices.
AB - Hybrid organic-inorganic and all-inorganic metal halide perovskites have been one
of the most intensively studied materials during the last few years. In
particular, research focusing on understanding how to tune the photoluminescence
features and to apply perovskites to optoelectronic applications has led to a
myriad of new materials featuring high photoluminescence quantum yields covering
the whole visible range, as well as devices with remarkable performances. Having
already established their successful incorporation in highly efficient solar
cells, the next step is to tackle the challenges in solid-state lighting (SSL)
devices. Here, the most prominent is the preparation of white-emitting devices.
Herein, we have provided a comprehensive view of the route towards perovskite
white lighting devices, including thin film light-emitting diodes (PeLEDs) and
hybrid LEDs (HLEDs), using perovskite based color down-converting coatings. While
synthesis and photoluminescence features are briefly discussed, we focus on
highlighting the major achievements and limitations in white devices. Overall, we
expect that this review will provide the reader a general overview of the current
state of perovskite white SSL, paving the way towards new breakthroughs in the
near future.
PMID- 29951684
TI - Metallosomes for biomedical applications by mixing molybdenum carbonyl
metallosurfactants and phospholipids.
AB - New supramolecular systems have been prepared by mixing molybdenum organometallic
metallosurfactants M(CO)5L and M(CO)4L2 {L = Ph2P(CH2)6SO3Na} with the
phospholipid phosphatidylcholine. The analysis of the resulting supramolecular
structures using dynamic light scattering and cryo-transmission electron
microscopy has shown the formation of different aggregates depending on the
metallosurfactant/phospholipid ratio, as well as a significantly different
behaviour between the two studied metallosurfactants. Mixed vesicles, with
properties very similar to liposomes, can be obtained with both compounds, and
are called metallosomes. The formation of the mixed aggregates has also been
studied by microfluidics using MeOH and EtOH as organic solvents, and it has been
observed that the size of the aggregates is strongly dependent on the organic
solvent used. In order to analyse the viability of these mixed systems as CO
Releasing Molecules (CORMs) for biomedical applications, the CO release was
studied by FT-IR spectroscopy, showing that they behave as photo-CORMs with
visible and ultraviolet light. Toxicity studies of the different mixed aggregate
systems have shown that metallosomes exhibit a very low toxicity, similar to
liposomes that do not contain metallosurfactants, which is well below the results
observed for pure metallosurfactants. Micro-FTIR microscopy using synchrotron
radiation has shown the presence of metallosurfactants in cells. The results of
this study show the influence of the length of the hydrocarbon chain on the
properties of these mixed systems, compared with previously reported data.
PMID- 29951685
TI - Visualization of nonemissive triplet species of Zn(ii) porphyrins through Cu(ii)
porphyrin emission via the reservoir mechanism in a porphyrin macroring.
AB - A macroring composed of three Cu(ii) porphyrins (CuP) and three slipped-cofacial
Zn(ii) porphyrin (ZnP2) dimers exhibited near-IR emission from the CuP part. The
emission lifetime of the macroring (15 MUs) was 500 times longer compared to that
of a Cu porphyrin monomer (e.g., Cu(ii)TPP; TPP = meso-tetraphenylporphyrin). The
observed emission is ascribed to emission via the reservoir mechanism from the
trip-doublet (2T1) state in CuP thermally activated from the T1 state of ZnP2,
which is located ca. 1030 cm-1 below the 2T1 state of CuP. The near-IR emission
of the macroring was significantly quenched by O2, whereas that of the Cu
porphyrin monomer was hardly quenched, indicating that the quenching event mainly
occurred on the T1 state of the ZnP2 parts. The nonemissive triplet state of a Zn
porphyrin at room temperature was visualized through emission from a neighboring
Cu porphyrin.
PMID- 29951686
TI - Predictability of the onset of spiking and bursting in complex chemical
reactions.
AB - For three complex chemical reactions displaying intricate dynamics, we assess the
effectiveness of a recently proposed quantitative method to forecast bursting and
large spikes, i.e. extreme events. Specifically, we consider predicting extreme
events in (i) a copper dissolution model where Bassett and Hudson experimentally
observed homoclinic (Shilnikov) chaos, (ii) a model derived from the mass action
law of chemical kinetics, and (iii) an autocatalator model. For these systems, we
describe how the alignment of Lyapunov vectors can be used to predict the
imminence of large-amplitude events and the onset of complex dynamics in chaotic
time-series of observables.
PMID- 29951687
TI - Seven-coordinate lanthanide complexes with a tripodal redox active ligand:
structural, electrochemical and spectroscopic investigations.
AB - The tripodal ligand TREN-(3,5-di-tert-butylsalicylidene)3 (H3L) was synthesized
and its tris(phenolato) lanthanide complexes L-Ln (Ln = NdIII, EuIII, TbIII,
GdIII, ErIII, YbIII and LuIII) were prepared. The X-Ray crystal structures
confirm that each metal ion resides in a similar monocapped octahedral geometry,
excluding water molecules from the coordination sphere. The coordination bond
distances are in agreement with the lanthanide contraction, with Ln-O bond
lengths in the range 2.139-2.216 A. The complexes show three reversible
monoelectronic oxidation waves, which are assigned to the successive oxidation of
the phenolate moieties to phenoxyl radicals. The L-Nd complex is the easiest to
oxidize, with E = 0.11, E = 0.21 and E = 0.34 V vs. Fc+/Fc, due to the larger
size of the lanthanide ion. The DeltaE1/2 value (DeltaE1/2 = E-E) is correlated
to the lanthanide radius, with values of 0.10 V for L-Nd and 0.22 V for L-Lu. The
monoradical species were persistent in solution, allowing for their
characterisation. All exhibit a distinct absorption band at around 445 nm due to
the phenoxyl pi-pi* transitions. The EPR spectrum of L-Lu+ consists of a single
resonance at giso = 1.999, confirming the radical nature of the oxidized product.
Most of the other complexes (L-Gd, L-Er, L-Yb) show a quenching of the LnIII
based resonances upon oxidation, indicative of magnetic interactions between the
metal and the radical spins. The L-Ln (L = Nd, Er, Yb) complexes exhibit a metal
based luminescence upon excitation of the ligand. A significant quenching of the
luminescence was observed upon radical formation: 92%, 83% and 79% respectively
for L-Nd+, L-Er+ and L-Yb+.
PMID- 29951688
TI - Stereoselective synthesis of 3-spiropiperidino indolenines via SN2-type ring
opening of activated aziridines with 1H-indoles/Pd-catalyzed spirocyclization
with propargyl carbonates.
AB - 3-Spiropiperidino indolenines have been synthesized via novel Lewis acid
catalyzed SN2-type ring opening of activated aziridines with 1H-indoles followed
by Pd-catalyzed dearomative spirocyclization with propargyl carbonates in up to
88% yields. The step and pot-economic transformation comprises sequential C-C, C
N, and C-C bond forming steps generating two stereogenic centers including an all
carbon quaternary stereocenter to furnish the products in diastereomerically pure
(dr >99 : 1) forms with excellent enantiomeric excess (ee up to >99%). The
synthetic versatility of the strategy has been illustrated by converting the
synthesized products into spirocyclic indolenine 2-piperidinones,
dihydropiperidines, and 5-alkynylated piperidines.
PMID- 29951689
TI - The influence of NHCs on C-Si and C-C reductive elimination: a computational
study of the selectivity of Ni-catalyzed C-H activation of arenes with
vinylsilanes.
AB - Density functional theory calculations were performed to investigate the
mechanism and origins of the NHC-controlled selectivity of Ni-catalyzed C-H
activation of arenes with vinylsilanes. The key to the selectivity is the
different impacts of NHCs on the C-Si/C-C reductive elimination of the square
planar/T-shaped intermediate.
PMID- 29951690
TI - [The future of emergency care in Germany].
PMID- 29951692
TI - Three dimensional patient-specific printed cutting guides for closing-wedge
distal femoral osteotomy.
AB - PURPOSE: Medial closing-wedge distal femoral osteotomy (MCWDFO) was used to treat
valgus knee malalignment combined with lateral compartment disease. The clinical
outcome of the osteotomy depends on the accurate correction of valgus
malalignment. The aim of this study was to evaluate the accuracy of a MCWDFO
assisted by three-dimensional (3D)-printed cutting guides and locking guides.
PATIENTS AND METHODS: Thirty-three consecutive patients (33 knees) were operated
on using the same MCWDFO. 3D-printed cutting guides and locking guides were used
to locate the osteotomy cut plane and to facilitate closing the wedge in 12
patients (3D-guide group). Another 21 patients (conventional group) underwent
MCWDFO following the conventional technique. The desired correction was defined
as a weight-bearing line (WBL) coordinate 50% of the width of the tibial plateau
from the medial tibial margin. The deviation between the planned and executed WBL
coordinate, surgical time and fluoroscopic time were compared. RESULTS: The mean
deviation between the planned and executed WBL coordinate was 4.9% in the 3D
guide group and 7.6% in the conventional group (P = 0.024). Shorter surgical time
was found in the 3D-guide group (mean, 77.7 minutes vs. mean, 96.5 minutes; P <
0.001), while the mean number of intra-operative fluoroscopic images was 6.1,
compared with 34.7 in the conventional group (P < 0.001). CONCLUSION: The use of
3D-printed cutting guides and locking guides can increase the precision of the
MCWDFO in patients with lateral compartment disease and valgus deformity, making
our surgery more efficiency and occupying less fluoroscopic time.
PMID- 29951693
TI - Transarterial Embolization with Small-Size Particles Loaded with Irinotecan for
the Treatment of Colorectal Liver Metastases: Results of the MIRACLE III Study.
AB - PURPOSE: This pilot study was performed to investigate safety and local tumor
control following transarterial embolization with small-size particles loaded
with irinotecan (DEB-IRI) in patients with colorectal liver metastases (CRLM).
MATERIALS AND METHODS: Patients with pretreated CRLM with mono- or bilobar
lesions involving less than 60% of the liver parenchyma and Eastern Cooperative
Oncology Group performance status 0 or 1 underwent superselective DEB-IRI
embolization with 40 um diameter embolic microspheres. RESULTS: Eighteen patients
(11 males, 7 females, median age 61 years) underwent 80 embolization procedures
(mean 4.4, range 2-12 per patient). No serious adverse events were reported
within 30 days. A total of 39 treatment-related AEs occurred across all
embolization procedures. No G4 or G5 treatment-related AEs occurred. Local tumor
control, defined as complete response, partial response, or stable disease, was
achieved in 16/18 (88.9%), 7/17 (41.2%), and 3/17 (17.6%) patients at 3, 6, and
12 months, respectively. Median liver progression-free survival was 5.9 months
(range 27-409 days), and median overall survival was 13.5 months. CONCLUSION: In
this small series, DEB-IRI embolization with small beads was demonstrated a safe
procedure in the treatment of patients with CRLM. The promising results in terms
of liver-specific progression-free survival and overall survival reported deserve
further confirmation in larger prospective trials. LEVEL OF EVIDENCE: Level 4,
case series.
PMID- 29951691
TI - Synthesis of interleukin 1 beta and interleukin 6 in human lymphocytes is
stimulated by tributyltin.
AB - Tributyltin (TBT) is a widespread environmental contaminant that is present in
human blood and other tissues. It has been shown to disrupt the immune function
of human natural killer (NK) cells and to alter the secretion of a number of pro
inflammatory cytokines from immune cells. Secretion of both interleukin 1beta (IL
1beta) and interleukin 6 (IL-6) from human lymphocytes can be increased dependent
upon the level of TBT exposure. This study shows that the TBT-induced increases
in secretion of both cytokines are due to TBT-induced increases in the synthesis
of these proteins and not simply because of the release of pre-existing cytokine.
Furthermore, the data indicate that these TBT-induced increases in IL-1beta and
IL-6 synthesis require MAP kinase signaling pathways. Additionally, elevated
synthesis of IL-1beta and IL-6 seen at the highest exposures to TBT (200, 200, 50
nM) were accompanied by increases in the mRNA for these cytokines. TBT-induced
increases in IL-1beta and IL-6 mRNAs were also shown to be dependent on MAP
kinase signaling. The study suggests that TBT has the capacity to increase immune
cell production of these 2 important pro-inflammatory cytokines and that this
increase is in part explained by increased mRNA for the cytokines.
PMID- 29951694
TI - A population pharmacokinetic/toxicity model for the reduction of platelets during
a 48-h continuous intravenous infusion of the histone deacetylase inhibitor
belinostat.
AB - PURPOSE: Belinostat is a second-generation histone deacetylase inhibitor (HDI)
predominantly metabolized by UGT1A1-mediated glucuronidation. Two common
polymorphisms (UGT1A1*28 and UGT1A1*60) were previously associated with impaired
drug clearance and thrombocytopenia risk, likely from increased drug exposure.
This latter phenomenon has been observed with other HDIs such as abexinostat,
panobinostat, romidepsin, and vorinostat. It was the intention of this brief
report to expand a population pharmacokinetic (PPK) model to include a
pharmacodynamic (PD) model describing the change in platelet levels in patients
with cancer administered belinostat as a 48-h continuous intravenous infusion,
along with cisplatin and etoposide. METHODS: The PPK/PD model developed here
introduced an additional rate constant to a commonly used mechanistic
myelosuppression model to better describe the maturation of megakaryocytes into
platelets before degradation and a feedback mechanism. The model employed a
proportional error model to describe the observed circulating platelet data.
RESULTS: Several covariates were explored, including sex, body weight, UGT1A1
genotype status, liver, and kidney function, but none significantly improved the
model. Platelet levels rebounded to baseline within 21 days, before the next
cycle of therapy. Simulations predicted that higher belinostat drug exposure does
cause lower thrombocyte nadirs compared to lower belinostat levels. However,
platelet levels rebound by the start of the next belinostat cycle. CONCLUSIONS:
This model suggests a q3week schedule allows for sufficient platelet recovery
before the next belinostat infusion is optimal.
PMID- 29951695
TI - Deviations in Peripheral Blood Cell Populations are Associated with the Stage of
Primary Biliary Cholangitis and Presence of Itching.
AB - To evaluate the role of Th17, Treg cells, activated T CD3+ and B CD19+
lymphocytes in primary biliary cholangitis (PBC) patients. 40 female patients
with PBC and 20 healthy donors were enrolled in this study. The percentages and
absolute counts of Th17, Treg, activated T CD3+, B CD19+, NK, NKT-like
lymphocytes were measured by flow cytometry. Our research revealed significantly
lower frequencies and absolute counts of CD4+CD25+FOXP3+ Treg cells (p < 0.0001),
higher percentages and absolute counts of Th17 cells (IL-17A+CD3+CD4+; p < 0.0001
and p = 0.009, respectively), CD3-/CD16+CD56+ NK cells (p < 0.0001 and p = 0.039,
respectively), CD3+/CD16+CD56+ NKT-like cells (p < 0.0001 and p = 0.048,
respectively). There were also higher percentages and numbers of B CD19+
lymphocytes (p = 0.002 and p = 0.001, respectively) and higher percentages and
absolute counts of activated B CD19+CD25+ cells (p = 0.007 and p = 0.002,
respectively). Moreover, we observed a statistically significant correlation
between the presence of itching and particular peripheral blood subpopulations in
PBC patients. Absolute counts of both CD4+CD3+ cells (p = 0.0119) and CD3+CD25+
cells (p = 0.0329) were lower in patients with pruritus. A similar dependency was
noted in reference to percentages of NKT-like cells (CD3+/CD16+CD56+; p = 0.0359)
and (CD3+) T lymphocytes (p = 0.0302). Th17 and Treg cells are involved in the
course of PBC. There is also the association between the pruritus and peripheral
blood subpopulations.
PMID- 29951696
TI - Analysis of Polymorphisms in the Mediator Complex Subunit 13-like (Med13L) Gene
in the Context of Immune Function and Development of Experimental Arthritis.
AB - The Mediator complex subunit 13-like (MED13L) protein is part of the multi
protein mediator complex and plays an important role in gene transcription.
Polymorphisms in the MED13L gene have been linked to congenital heart anomalies
and intellectual disabilities. Despite recent evidence of indirect links of
MED13L to cytokine release and inflammation, impact of genetic variations in
MED13L on immune cells remains unexplored. The B10.RIII and RIIIS/J mouse strains
vary in susceptibility to induced experimental autoimmune disease models. From
sequencing data of the two mouse strains, we identified six polymorphisms in the
coding regions of Med13L. Using congenic mice, we studied the effect of these
polymorphisms on immune cell development and function along with susceptibility
to collagen-induced arthritis, an animal model for rheumatoid arthritis.
Combining in vivo disease data, in vitro functional data, and computational
analysis of the reported non-synonymous polymorphisms, we report that genetic
polymorphisms in Med13L do not affect the immune phenotype in these mice and are
predicted to be non-disease associated.
PMID- 29951697
TI - Novel insights into global translational regulation through Pumilio family RNA
binding protein Puf3p revealed by ribosomal profiling.
AB - RNA binding proteins (RBPs) can regulate the stability, localization, and
translation of their target mRNAs. Among them, Puf3p is a well-known Pumilio
family RBP whose biology has been intensively studied. Nevertheless, the impact
of Puf3p on the translational regulation of its downstream genes still remains to
be investigated at the genome-wide level. In this study, we combined ribosome
profiling and RNA-Seq in budding yeast (Saccharomyces cerevisiae) to investigate
Puf3p's functions in translational regulation. Comparison of translational
efficiency (TE) between wild-type and puf3Delta strains demonstrates extensive
translational modulation in the absence of Puf3p (over 27% genes are affected at
the genome level). Besides confirming its known role in regulating mitochondrial
metabolism, our data demonstrate that Puf3p serves as a key post-transcriptional
regulator of downstream RBPs by regulating their translational efficiencies,
indicating a network of interactions among RBPs at the post-transcriptional
level. Furthermore, Puf3p switches the balance of translational flux between
mitochondrial and cytosolic ribosome biogenesis to adapt to changes in cellular
metabolism. In summary, our results indicate that TE can be utilized as an
informative index to interrogate the mechanism underlying RBP functions, and
provide novel insights into Puf3p's mode-of-action.
PMID- 29951698
TI - Mechanisms of RsaL mediated tolerance to ciprofloxacin and carbenicillin in
Pseudomonas aeruginosa.
AB - The Pseudomonas aeruginosa RsaL is a negative regulator of the quorum sensing
signal synthesis gene lasI. The expression of RsaL is directly activated by the
LasI cognate regulator LasR. Thus, RsaL and LasI-LasR (LasI/R) form a regulatory
loop. Further studies revealed that RsaL is a global regulator which controls the
expression of numerous genes through quorum sensing system dependent and
independent pathways. However, whether RsaL is involved in antibiotic tolerance
remains elusive. In this study, we found that the mutation of rsaL increased
bacterial tolerance to ciprofloxacin and carbenicillin. Through motif search,
gene expression analyses and electrophoretic mobility shift assays, we found that
RsaL directly represses the expression of the narK1K2GHJI operon, which is
involved in the tolerance to ciprofloxacin. We further demonstrated that the
narK1K2GHJI operon is directly regulated by LasR. In combination, our study
revealed a novel operon under the control of the RsaL, LasI/R regulatory loop.
PMID- 29951699
TI - The role of vasopressin in olfactory and visual processing.
AB - Neural vasopressin is a potent modulator of behaviour in vertebrates. It acts at
both sensory processing regions and within larger regulatory networks to mediate
changes in social recognition, affiliation, aggression, communication and other
social behaviours. There are multiple populations of vasopressin neurons within
the brain, including groups in olfactory and visual processing regions. Some of
these vasopressin neurons, such as those in the main and accessory olfactory
bulbs, anterior olfactory nucleus, piriform cortex and retina, were recently
identified using an enhanced green fluorescent protein-vasopressin (eGFP-VP)
transgenic rat. Based on the interconnectivity of vasopressin-producing and
sensitive brain areas and in consideration of autocrine, paracrine and
neurohormone-like actions associated with somato-dendritic release, we discuss
how these different neuronal populations may interact to impact behaviour.
PMID- 29951700
TI - Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal
stem cells against hydrogen-peroxide-induced oxidative stress.
AB - Survival of mesenchymal stem cells (MSCs) against oxidative stress and
inflammation is vital for effective stem cell therapy. The reactive oxygen
species (ROS) result in apoptosis and release of inflammatory mediators. Adipose
derived stem cells (ASCs) have shown promise for stem cell therapy owing to their
anti-inflammatory and anti-oxidant activity. Previously, we showed the benefits
of vitamin E against hydrogen peroxide (H2O2)-induced oxidative stress in rat
bone marrow-derived MSCs. In this study, we aim to evaluate the effect of vitamin
E treatment on porcine adipose-derived mesenchymal stem cells (pASCs) against
H2O2-induced oxidative stress. The oxidative stress was induced by treating pASCs
with 500 MUM H2O2 with or without vitamin E. Viability of pASCs is enhanced after
vitamin E treatment. In addition, reduced cellular toxicity, total NO level, PGE2
production and caspase-3 activity were observed after vitamin E treatment. Gene
expression analysis of vitamin E-treated pASCs showed down-regulated expression
for the genes associated with oxidative stress and apoptosis, viz., NOS2, Casp3,
p53, BAX, MDM2, NFkappaB, HIF1alpha and VEGF-A genes. On the other hand,
expression of anti-apoptotic and survival genes was up-regulated, viz., BCL2,
BCL2L1 and MCL1. Furthermore, phosphorylation of Akt was attenuated following
vitamin E treatment. The findings of this study may help in developing effective
stem cell therapy for the diseases characterized by the oxidative stress and
inflammation.
PMID- 29951701
TI - Assessment of Duodopa(r) effects on quality of life of patients with advanced
Parkinson's disease and their caregivers.
AB - The gold standard of treatment in Parkinson's disease (PD) is levodopa/carbidopa
whose long-term use induces motor and non-motor fluctuations and dyskinesias.
Continuous infusion of intrajejunal levodopa/carbidopa intestinal gel
(Duodopa(r)) reduces motor and non-motor symptoms and dyskinesias, and improves
the quality of life of patients. The aim of this open observational prospective
study was to evaluate the impact of Duodopa(r) on conditions of PD patients and
caregivers, and their quality of life. We enrolled 12 patients with advanced PD
and their caregivers. The PD patients were assessed at baseline, 3 and 6 months
after Duodopa(r) treatment initiation using Unified Parkinson's Disease Rating
Scale-Part III and IV (UPDRS-III and IV), Unified Dyskinesia Rating Scale
(UdysRS), Beck Depression Inventory (BDI-II), Hamilton Anxiety Rating Scale (HAM
A) and Parkinson's Disease Quality of Life Questionnaire (PDQ-39). The caregivers
were assessed, at the same time as the patients, using BDI-II, HAM-A, Caregiver
Burden Inventory (CBI) and SF-36 Health Status Questionnaire. Six months after
Duodopa(r) therapy, the scores of UPDRS-III and IV, UdysRS, BDI-II, HAM-A and PDQ
39 were significantly decreased (p < 0.01). After Duodopa(r) therapy, in
caregiver group the scores of BDI-II, HAM-A and CBI were significantly decreased
and the scores of SF-36 Health Status Questionnaire were significantly increased
(p < 0.01). A reduction of anxiety after therapy correlated with mental status
domains of SF-36 Health Status Questionnaire (r = 0.56). Overall, Duodopa(r) is
effective even in the short time to improve the clinical conditions of PD
patients and caregivers and their quality of life.
PMID- 29951702
TI - Autonomic function testing in Friedreich's ataxia.
AB - BACKGROUND: Friedreich ataxia (FRDA) is an inherited movement disorder which
manifests with progressive gait instability, sensory loss and cardiomyopathy.
Peripheral neuropathy is an established feature of FRDA. At neuropathological
examination, a depletion of large, myelinated axons is evident, but also
unmyelinated fibers are affected which may result in a variety of sensory and
autonomic signs and symptoms. Impaired temperature perception, vasomotor
disturbances of lower extremities and a high prevalence of urinary symptoms have
been documented in FRDA, but data from autonomic function testing in genetically
confirmed cases are lacking. METHODS: Genetically confirmed FRDAs were recruited
in an outpatient setting. In a screening visit, general and neurological
examination, laboratory testing, ECG and echocardiography were performed.
Autonomic functions were evaluated by means of systematic questionnaires (SCOPA
Aut, OHQ), skin sympathetic reflex and cardiovascular autonomic function testing
(CAFT). For the latter, a comparison with matched healthy controls was performed.
RESULTS: 20 patients were recruited and 13 underwent CAFT. Symptoms referred to
multiple autonomic domains, particularly bladder function, thermoregulation and
sweating were reported. SCOPA-Aut scores were significantly predicted by disease
severity. At CAFT, FRDAs did not differ from controls except for increased heart
rate at rest and during orthostatic challenge. Two patients had non-neurogenic
orthostatic hypotension (14%). Skin sympathetic responses were pathologic in 3
out of 10 patients (of whom 2 aged > 50). CONCLUSIONS: FRDA patients may
experience several autonomic symptoms and overall their burden correlates with
disease severity. Nonetheless, clinical testing shows no major involvement of
sudomotor and cardiovascular autonomic function.
PMID- 29951703
TI - Suppression of OsMDHAR4 enhances heat tolerance by mediating H2O2-induced
stomatal closure in rice plants.
AB - BACKGROUND: Monodehydroascorbate reductase (MDAR or MDHAR), which is responsible
for growth, development and stress response in plants, is a key enzyme in the
maintenance of the ascorbate acid (AsA) pool through the AsA-glutathione (AsA
GSH) cycle. High temperature affects a broad spectrum of cellular components and
metabolism including AsA-GSH cycle in plants. In rice, however, the detailed
roles of OsMDHAR4 in resistance against heat stress remains unclear. RESULTS:
Here, we report that OsMDHAR4 protein was localized to the chloroplasts. OsMDHAR4
expression was detected in all tissues surveyed and peaked in leaf blade.
OsMDHAR4 was responsive to multiple stresses and was relatively strongly induced
by heat treatment. In comparison with wild type, the osmdhar4 mutant exhibited
improved tolerance to heat stress, whereas OsMDHAR4 overexpression lines
exhibited enhanced sensitivity to heat stress. Moreover, we found that
suppression of OsMDHAR4 promoted stomatal closure and hydrogen peroxide
accumulation, and overexpression of OsMDHAR4 increased stomatal opening and
decreased hydrogen peroxide content in rice leaves. CONCLUSIONS: Taken together,
these results indicated that OsMDHAR4 negatively regulates tolerance to heat
stress by mediating H2O2-induced stomatal closure in rice.
PMID- 29951704
TI - Systemic concentrations of asymmetric dimethylarginine (ADMA) in chronic
obstructive pulmonary disease (COPD): state of the art.
AB - Experimental evidence suggests that oxidative stress (OS) may increase the
activity of arginine methylating enzymes that produce the endogenous nitric oxide
synthase inhibitor asymmetric dimethylarginine (ADMA). In addition, it is well
documented that OS can significantly decrease the synthesis and/or activity of
ADMA degrading enzymes, thus causing ADMA accumulation in biological fluids.
Recent reports have focused on circulating methylated arginine concentrations in
chronic obstructive pulmonary disease, a disease characterized by a significant
increase in OS. This review discusses the results of these studies and the
opportunities for further research in this area.
PMID- 29951706
TI - Natural infection of the beet webworm Loxostege sticticalis L. (Lepidoptera:
Crambidae) with three Microsporidia and host switching in Nosema ceranae.
AB - Three species of Microsporidia were identified from a population of the beet
webworm Loxostege sticticalis at prevalence rates of 35, 4, and 3%. The most
prevalent parasite (Tubulinosema sp.) was similar to Tubulinosema acridophagus
(99.8% ssrDNA sequence similarity) and was also isolated from the parasitoid
Lydella thompsoni (Diptera, Tachinidae) that emerged from the beet webworms. In
laboratory assays, spores of this Tubulinosema sp. showed an infection rate of up
to 80% for both L. sticticalis and Galleria mellonella larvae. The spores were
viable after 12 months of storage in dried infected cadavers. The second most
prevalent parasite was closely related to Nosema furnacalis and Nosema granulosis
(98.7% similarity). Fresh spores showed a 50% infection rate under laboratory
conditions. The third most abundant parasite was identified as the honeybee
pathogen Nosema ceranae (100% ssrDNA and 95-100% IGS similarity). In the
laboratory, fresh spores of N. ceranae isolated from beet webworm and honey bee
were infective to L. sticticalis larvae at the rates of 5 and 2%, respectively.
PMID- 29951705
TI - Improving the secretory expression of active recombinant AaIT in Pichia pastoris
by changing the expression strain and plasmid.
AB - Scorpion long-chain insect selective neurotoxin AaIT has the potential to be used
against agricultural insect pests. However, there is still a lack of a
heterologous gene expression system that can express AaIT efficiently. Here,
using X33 as the host strain and pPICZalphaA as the expression vector, one
transformant had the highest expression of recombinant AaIT (rAaIT) was obtained,
and secreted as high as 240 mg/l rAaIT in fed-batch fermentation. Secretory rAaIT
was purified by Ni2+-nitriloacetic affinity and CM chromatography, and 8 mg of
high purity rAaIT were purified from 200 ml fed-batch fermentation cultures.
Injecting silkworm (Bombyx mori Linnaeus) and Galleria mellonella larvae with
rAaIT resulted in obvious neurotoxin symptoms and led to death. These results
demonstrate that a large amount of anti-insect active rAaIT could be prepared
efficiently.
PMID- 29951707
TI - First detection of Baylisascaris procyonis in wild raccoons (Procyon lotor) from
Leipzig, Saxony, Eastern Germany.
AB - Baylisascaris procyonis is a zoonotic nematode mainly harbored by the North
American raccoon. It can cause severe neurological problems in paratenic hosts
and humans. In Germany, raccoons are spread throughout the country. However, the
presence of B. procyonis in the German raccoon population has not been thoroughly
studied. For this study, 32 wild raccoons were collected in the urban area
Leipzig, Saxony, Eastern Germany. Adult ascaroid nematodes were isolated from the
intestines and morphologically identified as B. procyonis. Species confirmation
was conducted through PCR. In total, adult B. procyonis worms were found in 24
raccoons. The results of the present study add new information about the presence
of the parasite in Saxony, Germany. Similarly, the results highlight the
importance of the raccoon as a reservoir of zoonotic parasites.
PMID- 29951708
TI - Calodium hepaticum (Nematoda: Capillariidae) in wild rodent populations from
Argentina.
AB - Calodium hepaticum (Nematoda; Capillariidae) is a parasitic nematode of mammals
with a cosmopolitan distribution. Adults of this nematode can infect the liver of
many mammalian species, including humans, but the main hosts are members of the
superfamily Muroidea. Among these, Rattus spp. have the highest apparent
prevalences reported worldwide. There are only two reports of C. hepaticum
infecting Sigmodontinae species (Muroidea: Cricetidae). In this survey, we
examined the occurrence of C. hepaticum in two assemblages of Sigmodontinae
rodents from Argentina (Santa Fe and Entre Rios provinces). The diagnosis was
made by morphological features, histopathological exam, and molecular
characterization of 18S ribosomal RNA gene region. Here, we show that C.
hepaticum is a common parasite of Sigmodontinae. We report the infection in six
species (all new hosts): Akodon azarae, Calomys callidus, Calomys venustus,
Oligoryzomys flavescens, Oligoryzomys nigripes, and Oxymycterus rufus. This is
the first report of C. hepaticum in Sigmodontinae rodents from Argentina and the
second record in this subfamily for South America. It is also the first
confirmation of C. hepaticum infection in Sigmodontinae by molecular diagnosis.
The genetic findings and the prevalences observed, together with the existing
information on C. hepaticum, lead us to propose that Rattus spp. brought C.
hepaticum to the New World exposing Sigmodontinae rodents, which are frequently
infected by this parasite. The high prevalence of infection in A. azarae (41.2%)
suggests that this host may be playing an important role in C. hepaticum dynamics
in the New World.
PMID- 29951710
TI - Reply to the letter to the Editor.
PMID- 29951709
TI - Early missed abortion is associated with villous angiogenesis via the HIF
1alpha/VEGF signaling pathway.
AB - PURPOSE: To analyze the effects of the hypoxia-inducible factor 1-alpha (HIF
1alpha)/vascular endothelial growth factor (VEGF) signaling pathway on villous
angiogenesis in early missed abortion. METHODS: Immunohistochemical assays were
performed to detect the expression of micro-vessel density (MVD), HIF-1alpha, and
VEGF in villous tissue samples from 30 missed abortions and 30 elective abortions
in early pregnancy. We further analyzed the correlation between HIF-1alpha/VEGF
and MVD. HTR8/SVneo cells were cultured under hypoxic (1%) or normoxic (20%)
conditions, tube formation was investigated, and protein and mRNA level of HIF
1alpha/VEGF were determined using western blot and qRT-PCR. Finally, HIF-1alpha
was knocked down with siRNA introduced into HTR8/SVneo cell line under hypoxia,
and HIF-1alpha/VEGF expression and HTR8/SVneo tube formation were investigated.
RESULTS: The expression of HIF-1alpha, VEGF, and MVD was lower in the missed
abortion than in the elective abortion group. Correlational analysis showed that
the expression of HIF-1alpha and VEGF was positively correlated with MVD in both
groups. The levels of HIF-1alpha/VEGF mRNA and protein in HTR8/SVneo cells were
significantly enhanced under hypoxia. HIF-1alpha knockdown with siRNA inhibited
HIF-1alpha/VEGF mRNA and protein levels of HTR8/SVneo cells induced by hypoxia.
Tube formation of HTR8/SVneo cells was significantly enhanced in hypoxic culture
and was inhibited by HIF-1alpha knockdown with siRNA. CONCLUSIONS: Our results
reveal a novel role for HIF-1alpha/VEGF in regulating villous angiogenesis in
early pregnancy and suggest that it may be a novel biomarker for missed abortion.
PMID- 29951711
TI - Effect of iron supplementation during early pregnancy on the development of
gestational hypertension and pre-eclampsia.
AB - OBJECTIVE: To investigate the association between iron supplementation during
early pregnancy and the presence of de novo hypertension after 20 weeks'
gestation (either gestational hypertension or pre-eclampsia). STUDY DESIGN:
Retrospective cohort study. METHODS: This study retrospectively reviewed the
medical records of non-anemic pregnant women who received first antenatal care at
the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital,
Navamindradhiraj University, Bangkok, Thailand, during the June 2009-December
2010 study period. All included women had blood pressure and urine albumin level
data that were recorded at each antenatal visit. The study population was divided
into one of the two following groups: iron supplementation starting at
gestational age (GA) < 16 weeks (study group) or GA >= 16 weeks (control group).
A comparison of the proportion of de novo hypertension arising after 20 weeks'
gestation was then performed between groups. RESULTS: Four hundred non-anemic
pregnant women were included, with 200 patients allocated to each groups. The
overall incidence of de novo hypertension after 20 weeks' gestation was 10%
(40/400), with significantly higher prevalence in the study group than that in
the control group [13.5% (27/200) vs. 6.5% (13/200); relative risk: 2.14, 95%, CI
1.22-3.73; p = 0.008]. None of the women in this study developed anemia at time
of delivery. There was no significant difference between groups for GA at
delivery, birth weight, or birth asphyxia. CONCLUSION: In our study population,
iron supplementation before 16 weeks' GA was significantly associated with
increased risk of developing de novo hypertension after 20 weeks' gestation.
PMID- 29951712
TI - Maternal, fetal and neonatal consequences associated with the use of crack
cocaine during the gestational period: a systematic review and meta-analysis.
AB - OBJECTIVE: Crack cocaine consumption is one of the main public health challenges
with a growing number of children intoxicated by crack cocaine during the
gestational period. The primary goal is to evaluate the accumulating findings and
to provide an updated perspective on this field of research. METHODS: Meta
analyses were performed using the random effects model, odds ratio (OR) for
categorical variables and mean difference for continuous variables. Statistical
heterogeneity was assessed using the I-squared statistic and risk of bias was
assessed using the Newcastle-Ottawa Quality Assessment Scale. Ten studies met
eligibility criteria and were used for data extraction. RESULTS: The crack
cocaine use during pregnancy was associated with significantly higher odds of
preterm delivery [odds ratio (OR), 2.22; 95% confidence interval (CI), 1.59
3.10], placental displacement (OR, 2.03; 95% CI 1.66-2.48), reduced head
circumference (- 1.65 cm; 95% CI - 3.12 to - 0.19), small for gestational age
(SGA) (OR, 4.00; 95% CI 1.74-9.18) and low birth weight (LBW) (OR, 2.80; 95% CI
2.39-3.27). CONCLUSION: This analysis provides clear evidence that crack cocaine
contributes to adverse perinatal outcomes. The exposure of maternal or prenatal
crack cocaine is pointedly linked to LBW, preterm delivery, placental
displacement and smaller head circumference.
PMID- 29951713
TI - The role of psychosocial resources for long-term breast, colorectal, and prostate
cancer survivors: prevalence and associations with health-related quality of
life.
AB - PURPOSE: Many long-term cancer survivors still have to adjust to possible adverse
consequences of the illness or treatment. Resources can play an important role in
this adjustment process, but research on this topic is limited, especially for
very long-term survivors. This study explores, which resources are most
frequently indicated by different subgroups of cancer survivors, and what role
resources play for functioning and health-related quality of life (HRQL) in
cancer survivors with and without recurrence. METHODS: The sample of 6030 breast,
colorectal, and prostate cancer survivors (5-16 years post-diagnosis) was
recruited in a German multi-regional population-based study. Personal resources
were assessed by a 27-item checklist; HRQL was assessed by the European
Organization for Research and Treatment of Cancer Quality of Life Questionnaire
Core 30 (EORTC QLQ-C30). General linear models were used to analyze associations
of resources with HRQL. RESULTS: Participants indicated on average 11.4 (SD 5.1)
resources as helpful. Family, activities with others, and partnership were
indicated most commonly overall, but frequencies varied according to age, sex,
and tumor site. Physical activity, health, professional help, calmness, hope,
optimism, and hobbies were most important in explaining HRQL variance. Cancer
survivors with recurrence and many resources were found to report similar HRQL as
survivors without recurrence and only few resources. CONCLUSIONS: The study
underlines the importance and situational variability of personal and social
resources for cancer survivors' HRQL, even years post-diagnosis. Not only the
availability, but also the individual perception and significance of resources
should be considered in follow-up cancer care.
PMID- 29951714
TI - Supportive care needs and associated factors among Chinese cancer survivors: a
cross-sectional study.
AB - PURPOSE: To investigate the unmet supportive care needs (SCNs) of Chinese cancer
survivors and to identify factors associated with the unmet SCNs of cancer
survivors. METHODS: A cross-sectional survey of Chinese cancer survivors was
conducted using validated scales of the Cancer Survivors Unmet Needs scale
(CaSUN), physical symptom concerns (Cancer Survivors Survey of Needs-CSSN
subscale), and a single-item measure of global quality of life (QoL) perception.
RESULTS: There were 330 participants, with a mean score of 7.1 (0-10) in overall
QoL. The reported rate of the 19 symptom concerns ranged from 19.4 to 72.2%. The
level of unmet SCNs (moderate and strong need) ranged from 12.1 to 59.1%. The top
five unmet needs included concerns about the cancer re-occurring (59.1%),
accessing the best medical care (52.7%), accessing complementary therapy services
(51.5%), changes to beliefs (48.2%), and survivor expectations (47.6%). The
strength of unmet SCNs was negatively correlated with participant age (P < 0.05),
average time since diagnosis (P < 0.05), and overall QoL (P < 0.01) and
positively correlated with all symptom concerns (all P < 0.001). CONCLUSIONS:
Study findings call attention to cancer survivors' unmet SCNs and related
factors. Underscored areas in developing survivorship care included paying
special attention to existential survivorship, empowering survivor management of
chronic symptoms, particularly for younger survivors, as well as for survivors
with poor QoL, and those with a shorter time since diagnosis. This tailored
survivorship care should be developed and delivered by a multidisciplinary team
to support cancer services, with a greater capacity to deliver individualized,
unmet SCN-driven care to survivors.
PMID- 29951715
TI - Enhanced Exciplex Emission of Pyrene Thin Films Doped by Perylene: Structural,
Photophysical and Morphological Investigation.
AB - The present work reports on the preparation of thin films of pyrene luminophors
doped by varying amounts of perylene by spin coating technique. The structural,
morphological, and photophysical properties of pyrene thin films have been
investigated as a function of perylene contents. X-ray diffraction studies of
doped thin films show well-defined peaks, and estimated crystallite size
decreases with increasing perylene content, due to the formation of closed packed
crystal structure. SEM images of pure pyrene revealed smooth, and compact and
separated crystals with amounts of perylene. The result of absorption spectra
showed decrease in intensity with perylene content. However, the fluorescence
spectra of pyrene containing higher amounts of perylene showed broad and
structureless exciplex emission at 510 nm. The emission colour of pyrene
luminophors tuned from blue to green by controlling the concentration of
perylene. The phenomenon of change in colour was seen due to efficient excitation
energy transfer from pyrene to perylene in thin films. It also found that the
intensity of exciplex emission increases with increasing concentration of
perylene is of high demand in fluorescent lamp as well as green organic light
emitting diodes.
PMID- 29951716
TI - Development of an efficient and sensitive analytical method for the determination
of copper at trace levels by slotted quartz tube atomic absorption spectrometry
after vortex-assisted dispersive liquid-liquid microextraction in biota and water
samples using a novel ligand.
AB - This study describes the determination of trace levels of copper by slotted
quartz tube atomic absorption spectrometry after dispersive liquid-liquid
microextraction. A ligand synthesized from the reaction of salicylaldehyde and 1
naphthylamine was used to form coordinate copper complex prior to extraction. All
parameters that influence the output of complex formation, extraction, and
instrumental measurement were optimized to enhance the absorbance signal of
copper. Under the optimum conditions, about 104-fold enhancement in sensitivity
was recorded over the conventional flame atomic absorption spectrometer,
corresponding to a 0.51 ng/mL detection limit. The percent relative standard
deviation calculated for the lowest concentration (4.8%) indicated high precision
for the experimental procedure. Accuracy and applicability of the optimum method
were determined by performing spiked recovery tests on urine, lake water, and
mineral water samples. Satisfactory recovery results were obtained between 82.2
and 106.3% at four different concentrations. Matrix matching method was also
performed to increase the accuracy of quantification, and the percent recovery
calculated for 175 ng/mL was 105.14%.
PMID- 29951717
TI - Training Methods for Delivering Difficult News in Genetic Counseling and Genetics
Residency Training Programs.
AB - Genetic counselors and clinical geneticists are often in the position of
delivering difficult news (DDN) to patients and families. Many studies show that
healthcare providers require major improvement in the skills needed in DDN in a
manner that is satisfactory to their patients. The purpose of this study was to
assess the amount and methodology of DDN training received by genetic counselors
and medical genetics residents in their training programs, such as observations
of DDN or attending didactic lectures. To our knowledge, there is no previous
assessment or study of DDN training in genetic counselor and medical genetics
residency programs; therefore, we aim to both assess and compare the training in
DDN received by genetic counselors and by genetics residents and determine
whether there is a desire for recommendations on DDN training. We invited genetic
counseling (GC) and genetics residency program directors to participate in an
online survey designed to assess coursework, clinical experiences, and directors'
attitudes toward teaching DDN. Response rate was 85% (28/33) for GC program
directors and 26% (14/53) for genetics residency program directors. One hundred
percent of GC and genetics residency directors who responded to the survey agreed
that it is important for genetic counselors and medical geneticists to be able to
deliver difficult news effectively and that training programs should formally
teach students how to deliver difficult news. Six of the eight common teaching
methods are used by at least 75% of GC programs while two of eight are used by at
least 75% of genetics residency programs. Seventy-nine percent of GC and 93% of
genetics residency program directors agree that there should be recommendations
on how to teach students to deliver this news. Our results show that techniques
for DDN are integrated more fully into GC program curricula than genetics
residency curricula. Directors of both types of programs desire recommendations
and more standardized education for training students to deliver difficult news.
PMID- 29951718
TI - Utilization of Genetic Testing for RET Mutations in Patients with Medullary
Thyroid Carcinoma: a Single-Center Experience.
AB - Medullary thyroid carcinoma (MTC) is often due to the hereditary condition
multiple endocrine neoplasia type 2 (MEN2) and it is standard of care to offer
genetic testing to all diagnosed patients. This study used the Kaiser Permanente
integrated medical record system to identify patients at risk for MEN2, assess
adherence to clinical practice guidelines, and offer genetic counseling and
testing. A query of the electronic medical records system identified patients
with MTC. All patients with MTC who had not had RET gene testing, as well as
patients who had positive RET gene testing, but had not yet had genetic
counseling, were contacted and offered a genetics consultation. The query
identified 142 patients with MTC. Fifty-six (40%) of those patients had not had
the RET testing that all endocrine professional groups recommend. Forty-nine
patients were eligible for the outreach, and, from this, 14 patients were
scheduled for genetic counseling. Of the 94 individuals at our institution who
had RET genetic testing, 25 (27%) were positive for a mutation. Of the 82
apparently sporadic cases, 13 (16%) carried a RET mutation. A family history of
endocrine cancer and younger age at diagnosis significantly increased the risk
carrying a RET mutation. However, approximately half of RET-positive patients did
not have a significant family history of cancer and one-third were over age 50 at
diagnosis. This study concludes that a significant proportion of patients with
MTC are not receiving standard of care genetic testing and reinforces previous
research that sporadic-appearing cases of MTC are often, in fact, hereditary.
PMID- 29951720
TI - The mind-body problem in the philosophy of mind and cognitive neuroscience: a
physicalist naturalist solution.
AB - Using an analysis of a voluntary action caused by a visual perception, I suggest
that the three fundamental characteristics of this perception (being conscious,
self-conscious, and provided with a content) are neurologically implemented by
three distinct higher order properties of brain dynamics. This hypothesis allows
me to sketch out a physicalist naturalist solution to the mind-body problem.
According to this solution, primary phenomenal consciousness is neither a non
physical substance, nor a non-physical property but simply the "format" that the
brain gives to a part of its dynamics in order to obtain a fine tuning with its
environment when the body acts on it.
PMID- 29951719
TI - Genetic Counselors' Perspectives About Cell-Free DNA: Experiences, Challenges,
and Expectations for Obstetricians.
AB - The expansion of cell-free fetal DNA (cfDNA) screening for a larger and diverse
set of genetic variants, in addition for use among the low-risk obstetric
population, presents important clinical challenges for all healthcare providers
involved in the delivery of prenatal care. It is unclear how to leverage the
different members of the healthcare team to respond to these challenges. We
conducted interviews with 25 prenatal genetic counselors to understand their
experience with the continued expansion of cfDNA screening. Participants
supported the use of cfDNA screening for the common autosomal aneuploidies, but
noted some reservations for its use to identify fetal sex and microdeletions.
Participants reported several barriers to ensuring that patients have the
information and support to make informed decisions about using cfDNA to screen
for these different conditions. This was seen as a dual-sided problem, and
necessitated additional education interventions that addressed patients seeking
cfDNA screening, and obstetricians who introduce the concepts of genetic risk and
cfDNA to patients. In addition, participants noted that they have a professional
responsibility to educate obstetricians about cfDNA so they can be prepared to be
gatekeepers of counseling and education about this screening option for use among
the general obstetric population.
PMID- 29951721
TI - Ocular flutter, generalized myoclonus, and ataxia associated with anti-GM1, GD1a,
and GD1b antibodies in a 6-year-old child.
PMID- 29951722
TI - Hyponatremia and mortality among very elderly residents in a geriatric health
service facility.
AB - INTRODUCTION: Hyponatremia is common among elderly patients. This study aimed to
examine the prognostic value of hyponatremia among elderly residents in a
geriatric facility. METHODS: We retrospectively examined the association between
serum sodium levels and mortality among 118 residents (82% female, mean age 85.5
years) in a single geriatric health service facility. We defined hyponatremia as
Na < 135 mEq/L. On the basis of single measurements of serum sodium at periodic
examinations, the patients were divided into hyponatremia and non-hyponatremia
groups. Multivariable Cox proportional hazards models were used to evaluate the
effect of hyponatremia on mortality from May 2005 to April 2007. RESULTS: Thirty
three patients (28%) had hyponatremia. Over a 1-year follow-up period, the
cumulative survival rate was significantly lower in patients with hyponatremia
than in those without hyponatremia. In a multivariate analysis, including
traditional risk factors for death, hyponatremia was associated with an increased
mortality risk (adjusted hazard ratio 2.73; 95% confidence interval 1.01-5.16; p
= 0.047). CONCLUSIONS: Hyponatremia is common and is a predictor of mortality in
the near future among very elderly residents of a geriatric facility.
PMID- 29951723
TI - Risk factors for increased left ventricular hypertrophy in patients with chronic
kidney disease: findings from the CKD-JAC study.
AB - BACKGROUND: Although left ventricular hypertrophy (LVH) has been established as a
predictor of cardiovascular events in chronic kidney disease (CKD), the
relationship between the prevalence of LVH and CKD stage during the pre-dialysis
period has not been fully examined. METHODS: We measured left ventricular mass
index (LVMI) in a cross-sectional cohort of participants in the Chronic Kidney
Disease Japan Cohort (CKD-JAC) study to identify factors that are associated with
increased LVMI in patients with stage 3-5 CKD. RESULTS: We analyzed the baseline
characteristics in 1088 participants (male 63.8%, female 36.2%). Diabetes
mellitus was the underlying disease in 41.7% of the patients, and mean age was
61.8 +/- 11.1 years. LVH was detected in 23.4% of the patients at baseline. By
multivariate logistic analysis, independent risk factors for LVH were past
history of cardiovascular disease [odds ratio (OR) 2.364; 95% confidence interval
([CI) 1.463-3.822; P = 0.0004], body mass index (OR 1.108; 95% CI 1.046-1.173; P
= 0.0005), systolic blood pressure (OR 1.173; 95% CI 1.005-1.369; P = 0.0433),
urinary albumin (OR 1.425; 95% CI 1.028-1.974; P = 0.0333), and serum total
cholesterol level (OR 0.994; 95% CI 0.989-0.999; P = 0.0174). CONCLUSION: The
cross-sectional baseline data from the CKD-JAC study shed light on the
association between LVH and risk factors in patients with decreased renal
function. Further longitudinal analyses of the CKD-JAC cohort are needed to
evaluate the prognostic value of LVH in CKD patients.
PMID- 29951724
TI - Relationship between abdominal adiposity and incident chronic kidney disease in
young- to middle-aged working men: a retrospective cohort study.
AB - BACKGROUND: Obesity is a risk factor for the development of chronic kidney
disease (CKD). However, it remains to be fully examined whether fatness is more
useful in predicting incident CKD. We aimed this study to determine the
association of body fat, body mass index and waist circumference (WC) with
subsequent changes in estimated glomerular filtration rate (eGFR) and incident
CKD in young- to middle-aged working men. METHODS: We analyzed data from annual
health check-up in male workers aged from 20 to 60 years with basal eGFR of 60-90
mL/min/1.73 m2. Cut-off values of parameters and odds ratio (OR) for the incident
CKD were calculated by receiver operator characteristics analysis andchi 2 test,
respectively. We also tested trends of changes in eGFR according to changes in WC
in each age decade. RESULTS: There were 8,015 men participants. During the 5-year
follow-up, 11.0% of the participants (N = 878) had developed to incident CKD.
When basal WC was greater than 80.0 cm, which was decided by Youden's Index,
there was a significantly higher risk of incident CKD [OR 1.57 (95% confident
interval 1.35-1.84)]. Changes in WC over 5 years were significantly related to
eGFR decline in young men (< 40 years old) with normal blood pressures and
normoglycemia. CONCLUSIONS: These findings suggest that WC > 80.0 cm is a risk
factor for incident CKD and strongly associated with a decline in eGFR in the
young- to middle-aged working healthy men.
PMID- 29951725
TI - Acute phosphate nephropathy leading to graft failure.
PMID- 29951726
TI - Toxic Metal and Trace Element Concentrations in Blood and Outcome of In Vitro
Fertilization in Women.
AB - The aim of this study was to investigate the association of trace element and
toxic metal concentrations in blood and the outcome of in vitro fertilization
(IVF). The study included 104 consecutive patients that underwent assisted
reproductive technology (ART) procedures. The following parameters were
determined: cadmium (Cd), mercury (Hg), arsenic (As), and lead (Pb); and copper
(Cu), zinc (Zn), selenium (Se), and magnesium (Mg). Serum samples were obtained
before commencing stimulation. Patients with smoking habit had significantly
higher Pb concentrations (P = 0.022), as well as higher concentrations of As and
Hg but not significantly. All subjects were divided into groups of pregnant and
nonpregnant patients. Pregnant patients had lower mean values of Mg (P = 0.009),
As (P < 0.05), and Pb (P = 0.034), compared to nonpregnant, and a significant
correlation between pregnancy outcome and concentrations of Mg, Cd, and Pb was
found. Women who had had delivered had lower Mg (P = 0.009) and Cd (P = 0.014)
concentrations. There was a significant correlation of the negative outcome of
IVF procedure with higher concentrations of Pb (P = 0.046) and Cd (P = 0.012). In
conclusion, our results suggest that there is a difference in Mg, Pb, and Cd
concentrations between pregnant and nonpregnant women. There was no association
between toxic metals and number and quality of oocytes and embryos, while there
was with fertilization rate. Concerning trace elements, we did not find the
correlation of trace elements with oocyte number and quality, nor with a number
of fertilized oocytes, except for Cu. Patients who were pregnant had lower
concentrations of Mg.
PMID- 29951727
TI - Subchronic Administration of High-Dose Sodium Fluoride Causes Deficits in
Cerebellar Purkinje Cells But Not Motor Coordination of Rats.
AB - Fluoride is frequently added to drinking water supplies, various food products,
toothpaste, and mouth rinses to prevent tooth damage. However, at high
concentrations, fluoride can cause fluorosis and damage to the brain tissue due
to its excitotoxicity and oxidative stress effects. The damage of the Purkinje
cells of the cerebellum can lead to motor coordination disorders. The present
study aimed at investigating the effects of sodium fluoride on the motor
coordination and the number of Purkinje cells of the cerebellum of rats. Adult
male Wistar rats were divided into four groups, namely a control group which
received reverse osmosis distilled water and three treated groups which received
sodium fluoride at doses of 5, 10, or 20 mg/kg bw. The treatment lasted for 30
days. The motor coordination of the rats was examined using a rotarod prior and
subsequent to the treatments. The number of Purkinje cells was estimated using
physical fractionator design. The numbers of Purkinje cells of the F10 and F20
groups were significantly lower than that of the control group. No significant
differences in the results of the motor coordination test were found. The
administration of sodium fluoride at doses of 10 and 20 mg/kg bw caused a
decrease in the number of Purkinje cells of the cerebellum in rats.
PMID- 29951728
TI - Myocyte-Damaging Effects and Binding Kinetics of Boronic Acid and Epoxyketone
Proteasomal-Targeted Drugs.
AB - The proteasome inhibitors bortezomib, carfilzomib, and ixazomib, which are used
in the treatment of multiple myeloma have greatly improved response rates.
Several other proteasome inhibitors, including delanzomib and oprozomib, are in
clinical trials. Carfilzomib and oprozomib are epoxyketones that form an
irreversible bond with the 20S proteasome, whereas bortezomib, ixazomib, and
delanzomib are boronic acids that form slowly reversible adducts. Several of the
proteasome inhibitors have been shown to exhibit specific cardiac toxicities. A
primary neonatal rat myocyte model was used to study the relative myocyte
damaging effects of five proteasome inhibitors with a view to identifying
potential class differences and the effect of inhibitor binding kinetics.
Bortezomib was shown to induce the most myocyte damage followed by delanzomib,
ixazomib, oprozomib, and carfilzomib. The sensitivity of myocytes to proteasome
inhibitors, which contain high levels of chymotrypsin-like proteasomal activity,
may be due to inhibition of proteasomal-dependent ongoing sarcomeric protein
turnover. All inhibitors inhibited the chymotrypsin-like proteasomal activity of
myocyte lysate in the low nanomolar concentration range and exhibited time
dependent inhibition kinetics characteristic of slow-binding inhibitors. Progress
curve analysis of the inhibitor concentration dependence of the slow-binding
kinetics was used to measure second-order "on" rate constants for binding. The
second-order rate constants varied by 90-fold, with ixazomib reacting the
fastest, and oprozomib the slowest. As a group, the boronic acid drugs were more
damaging to myocytes than the epoxyketone drugs. Overall, inhibitor-induced
myocyte damage was positively, but not significantly, correlated with their
second-order rate constants.
PMID- 29951729
TI - The ventricular residence time distribution derived from 4D flow particle
tracing: a novel marker of myocardial dysfunction.
AB - 4D flow cardiac magnetic resonance (CMR) imaging allows visualisation of blood
flow in the cardiac chambers and great vessels. Post processing of the flow data
allows determination of the residence time distribution (RTD), a novel means of
assessing ventricular function, potentially providing additional information
beyond ejection fraction. We evaluated the RTD measurement of efficiency of left
and right ventricular (LV and RV) blood flow. 16 volunteers and 16 patients with
systolic dysfunction (LVEF < 50%) underwent CMR studies including 4D flow. The
RTDs were created computationally by seeding virtual 'particles' at the inlet
plane in customised post-processing software, moving these particles with the
measured blood velocity, recording and counting how many exited per unit of time.
The efficiency of ventricular flow was determined from the RTDs based on the time
constant (RTDc = - 1/B) of the exponential decay. The RTDc was compared to
ejection fraction, T1 mapping and global longitudinal strain (GLS). There was a
significant difference between groups in LV RTDc (healthy volunteers 1.2 +/- 0.13
vs systolic dysfunction 2.2 +/- 0.80, p < 0.001, C-statistic = 1.0) and RV RTDc
(1.5 +/- 0.15 vs 2.0 +/- 0.57, p = 0.013, C-statistic = 0.799). The LV RTDc
correlated significantly with LVEF (R = - 0.84, P < 0.001) and the RV RTDc had
significant correlation with RVEF (R = - 0.402, p = 0.008). The correlation
between LV RTDc and LVEF was similar to GLS and LVEF (0.926, p < 0.001). The
ventricular residence time correlates with ejection fraction and can distinguish
normal from abnormal systolic function. Further assessment of this method of
assessment of chamber function is warranted.
PMID- 29951730
TI - Patterns of Spiritual Connectedness during Adolescence: Links to Coping and
Adjustment in Low-Income Urban Youth.
AB - Religiosity and spirituality are influential experiences that buffer adverse
effects of stressors. Spirituality typically declines during adolescence,
although not universally. Using Latent Class Growth Analysis, we examined changes
in spiritual connectedness among 188 early (52% female; M age = 10.77, SD = 0.65
years) and 167 middle (56% female; M age = 13.68, SD = 0.82 years) predominantly
African American adolescents participating in a 4-year longitudinal study. Three
distinct profiles of spiritual connectedness emerged: low and steady, moderate
with declines over the study period, and high and steady. Profile distributions
varied across developmental level: there were more early adolescents in the high
and steady profile and more middle adolescents in the decliner profile. Youth in
the high and steady profile evidenced more goal-directedness and life
satisfaction and more effective emotion management and coping strategies than
youth in other profiles. Contributions to the positive development literature are
discussed.
PMID- 29951732
TI - Comment on: "Activating Autophagy as a Therapeutic Strategy for Parkinson's
Disease".
PMID- 29951731
TI - Tetramethylpyrazine Protects Against Early Brain Injury and Inhibits the PERK/Akt
Pathway in a Rat Model of Subarachnoid Hemorrhage.
AB - Neuronal apoptosis is a potentially fatal pathological process that occurs in
early brain injury (EBI) after subarachnoid hemorrhage (SAH). There is an urgent
need to identify effective therapeutics to alleviate neuronal apoptosis.
Tetramethylpyrazine (TMP), as an important component of the Chinese traditional
medicinal herb Ligusticum wallichii, has been widely used in China to treat
cerebral ischemic injury and confer neuroprotection. In the present work, we
investigate whether TMP can reduce EBI following SAH in rats, specifically via
inactivating the PERK/Akt signaling cascade. One hundred twenty-five male Sprague
Dawley rats were used in the present study. TMP was administered by intravenous
(i.v.) injection, and the Akt inhibitor MK2206 was injected
intracerebroventricularly (i.c.v.). SAH grade, neurological scores, and brain
water content were measured 24 h after SAH. Neuronal apoptosis was visualized by
Fluoro-Jade C (FJC) staining. Western blotting was used to measure the levels of
PERK, p-PERK, eIF2alpha, p-eIF2alpha, Akt, p-Akt, Bcl-2, Bax, and cleaved caspase
3. Our results showed that TMP effectively reduced neuronal apoptosis and
improved neurobehavioral deficits 24 h after SAH. Administration of TMP reduced
the abundance of p-PERK and p-eIF2alpha. In addition, TMP increased the p-Akt
level and the Bcl-2/Bax ratio and decreased the level of cleaved caspase-3. The
selective Akt inhibitor MK2206 abolished the anti-apoptotic effect of TMP at 24 h
after SAH. Collectively, these results indicate that Akt-related anti-apoptosis
through the PERK pathway is a major, potent mechanism of EBI. Further
investigation of this pathway may provide a basis for the development of TMP as a
clinical treatment.
PMID- 29951733
TI - Author's Reply to Segura-Aguilar: Autophagosome maturation not autophagy
induction is impaired in neurodegeneration.
PMID- 29951734
TI - Efficacy of Umeclidinium/Vilanterol in Elderly Patients with COPD: A Pooled
Analysis of Randomized Controlled Trials.
AB - OBJECTIVE: The aim of this pooled analysis was to assess the efficacy and safety
of umeclidinium/vilanterol (UMEC/VI) 62.5/25 ug dual bronchodilation versus
placebo in elderly symptomatic patients with chronic obstructive pulmonary
disease (COPD). METHODS: We conducted a post hoc pooled analysis of data from 10
randomized controlled trials (RCTs). Change from baseline (CFB) in trough forced
expiratory volume in 1 s (FEV1), proportion of FEV1 responders (>= 100-mL
increase from baseline), and safety were analyzed in patients aged < 65, >= 65,
and >= 75 years on Days 28, 56, and 84 (12-week analysis of parallel-group design
studies), Days 28, 56, 84, 112, 140, 168, and 169 (24-week analysis of parallel
group design studies), and Days 2, 42, and 84 (12-week analysis of crossover
design studies). RESULTS: The UMEC/VI intent-to-treat (ITT) populations comprised
2246, 1296, and 472 patients in the 12-week parallel-group, 24-week parallel
group, and 12-week crossover analysis, respectively (>= 65 years: 36-44%; >= 75
years: 7-11%). The placebo ITT populations comprised 528, 280, and 505 patients,
respectively (>= 65 years: 37-41%; >= 75 years: 5-11%). Significant improvements
in trough FEV1 and significantly greater proportions of FEV1 responders were seen
with UMEC/VI compared with placebo in all analyses regardless of patient age or
timepoint considered (p <= 0.023), except Day 84 trough FEV1 CFB in the 12-week
crossover analysis in patients aged >= 75 years (p = 0.064). UMEC/VI safety
profile was similar to placebo in all age groups. CONCLUSIONS: In this pooled
analysis of RCT data, once-daily UMEC/VI was well tolerated and provided
clinically significant lung function benefits compared with placebo in younger
and older patients with COPD. FUNDING: GlaxoSmithKline (study 208125).
PMID- 29951735
TI - Re-induction chemotherapy using FLAG-mitoxantrone for adult patients with
relapsed acute leukemia: a single-center experience from United Arab Emirates.
AB - We studied the outcome of 47 adult patients with relapsed acute leukaemia (AML =
25 and ALL = 22) treated with FLAG-mitoxantrone regimen. Median time to relapse
was 10.7 months (range 1.9-27.7). Complete remission (CR2) was 60.1% which was
significantly more frequent in ALL compared to AML (P = 0.049). WBC count < 100 *
109/L at initial diagnosis and time to relapse > 1 year were significantly
predictor for CR2 in AML (P = 0.005 for both). Induction death was significantly
higher in ALL compared to AML (P = 0.039). Median follow-up was 4.0 months (0.9
119.8) for AML and 2.1 months (range 0.6-118.1) for ALL. Nine patients underwent
allogeneic stem-cell transplantation (allo-SCT). Estimated overall survival (OS)
at 12 and 18 months was 60.5 and 34.6%, respectively, for AML, and 39.9 and
29.9%, respectively, for ALL. For AML patients failure to achieve CR, WBC count
at initial diagnosis > 5 * 109/L and poor cytogenetic risk group was significant
predictors of poor OS (P = 0.010, P = 0.025, and P = 0.015, respectively). For
ALL patients failure to achieve of CR, WBC count at relapse < 5 * 109/L (CR
patients) and lack of any type of consolidation therapy were significant
predictor of poor OS (P < 0.001, P = 0.008, P = 0.008, respectively).
PMID- 29951736
TI - Molecular Cloning and Biochemical Characterization of Iron Superoxide Dismutase
from Leishmania braziliensis.
AB - Leishmaniasis is one of the most important neglected tropical diseases, with a
broad spectrum of clinical manifestations. Among the clinical manifestations of
the disease, cutaneous leishmaniasis, caused by species of Leishmania
braziliensis, presents wide distribution in Brazil. In this work, we performed
the cloning, expression, and purification of the enzyme superoxide dismutase of
Leishmania braziliensis (LbSOD-B2) considered a promising target for the search
of new compounds against leishmaniasis. In vitro assays based on pyrogallol
oxidation showed that LbSOD-B2 is most active around pH 8 and hydrogen peroxide
is a LbSOD-B2 inhibitor at low millimolar range (IC50 = 1 mM).
PMID- 29951737
TI - The Development of Bacterial Carboxylesterase Biological Recognition Elements for
Cocaine Detection.
AB - Enzyme recognition element-based biosensors are very attractive for biosensor
application due to a variety of measurable reaction products arising from a
catalytic process. In this study, biosensor recognition elements have been
developed via engineer bacterial enzymes (carboxylesterases (CEs)) which will
used for narcotic detection because of their role in narcotics metabolism. The
modification (insertion of cys-tag) allows the enzyme to bind into a transducer
surface of a biosensor which will translate the reaction product into the
detection system. The results demonstrate the successful isolation, cloning,
expression, and purification of recombinant (pnbA1 and pnbA2), and engineered
(pnbA1-cys and pnbA2-cys) bacterial carboxylesterases. Enzyme capability to
hydrolyse cocaine into benzoylecgonine and methanol was quantified using HPLC.
Both enzymes showed broad maximal activity between pH (8.0, 8.5, and 9.0), PnbA1
temperature stability ranging between (25 and 45 degrees C); however, PnbA2
stability range was (25-40 degrees C). Insertion of cys-tag at the N-terminal of
the enzyme did not limit entrance to the active site which is located at the base
of a cavity with dimensions 20 by 13 by 18 A, and did not prevent substrate
hydrolysis. Bacterial carboxylesterases pnbA1 and pnbA2 mimic hCE1 and not hCE2
in its reaction pathways hydrolysing cocaine into benzoylecgonine and methanol
rather than ecgonine methyl ester and benzoic acid. These results are the first
experimental evidence confirming the capability of bacterial carboxylesterase to
hydrolyse cocaine into its main metabolites, therefore opening up the possibility
to use these enzymes in numerous biotechnological applications in addition to a
cocaine biosensor.
PMID- 29951738
TI - [Early diagnosis and localization of cancer by liquid biopsy].
PMID- 29951739
TI - Multiple endpoints in clinical trials - severe adverse event potentials from the
medical biometrician's perspective.
AB - The clinical evaluation of medicinal drugs follows strict guidelines both
concerning the clinical as well as the pharmaceutical implementation perspective.
Furthermore, it underlies similarly rigid implementation guidelines from the
medical biometry perspective, pertaining from the choice of minimum necessary
patient numbers to the primary statistical evaluation concept. The latter,
however, require the explicit parameterization of clinical endpoints, alongside
which efficacy and effectiveness of the drug under investigation will then be
tested for the trial at hand. In most settings, the choice of these endpoints
directly arises from the clinical rationale of the investigation, but is then
complemented with a rather rigid recommendation from the trial statistician's
perspective, that is the restriction to only one primary clinical endpoint. The
use of several parallel clinical endpoints cannot only end up in inconsistent or
even contradictory clinical decision rules, but can also have crucial impact on
the overall number of patients necessary in the statistical analysis of the
clinical trial under consideration. Although the combination of multiple parallel
endpoints may provide a solution in some clinical trial settings, the most
effective recommendation can be seen in specifying only one primary clinical
endpoint of maximum clinical relevance for the therapeutic intention at hand.
PMID- 29951740
TI - Induction and Detection of Autophagy in Aged Hematopoietic Stem Cells by Exposing
Them to Microvesicles Secreted by HSC-Supportive Mesenchymal Stromal Cells.
AB - Autophagy is an important cellular process for maintenance of quality and
functionality of cells. This happens through repair and renewal of cellular
components like proteins and mitochondria. Reduction in autophagy process in aged
hematopoietic stem cells (HSCs) leads to their compromised stemness and self
renewal capacity, and consequently, their applicability in various regenerative
therapies also reduces. HSC functions are regulated by their microenvironment,
known as "HSC niche," which comprises of mesenchymal stromal cells (MSCs),
osteoblasts, endothelial cells, etc. In this niche, the MSCs are known to closely
interact with the HSCs, and therefore, they can directly influence the stem cell
fate. In our earlier studies, we have demonstrated that young MSCs or aged MSCs
rejuvenated by treating them with LY294002, a PI3K inhibitor (rescued aged MSCs),
rejuvenate aged HSCs via intercellular transfer of microvesicles (MVs) harboring
autophagy-inducing mRNAs.Here, we describe the protocol for induction of
autophagy in aged HSCs by incubating them with microvesicles (MVs) collected from
young MSCs or rescued aged MSCs. We also describe the protocols for determination
of autophagy levels in these HSCs.
PMID- 29951741
TI - Decellularized bSIS-ECM as a Regenerative Biomaterial for Skin Wound Repair.
AB - Tissue engineering-based regenerative applications can involve the use of stem
cells for the treatment of non-healing wounds. Multipotent mesenchymal stem cells
have become a focus of skin injury treatments along with many other injury types
owing to their unprecedented advantages. However, there are certain limitations
concerning the solo use of stem cells in skin wound repair. Natural bioactive
extracellular matrix-based scaffolds have great potential for overcoming these
limitations by supporting the regenerative activity and localization of stem
cells. This chapter describes the use of bone marrow mesenchymal stem cells
together with decellularized bovine small intestinal submucosa (SIS), for the
treatment of a critical-sized full-thickness skin defect in a small animal model.
PMID- 29951742
TI - Abaloparatide is an Effective Treatment Option for Postmenopausal Osteoporosis:
Review of the Number Needed to Treat Compared with Teriparatide.
AB - Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective
activator of the parathyroid hormone receptor type 1 signaling pathway. In the
Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous ABL
reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic
fracture compared with placebo and of major osteoporotic fracture compared with
teriparatide. To further evaluate the effectiveness of ABL, we calculated the
number needed to treat (NNT) to prevent one fracture using ACTIVE data. To
estimate the potential effectiveness of ABL in populations at higher fracture
risk than in ACTIVE, we calculated NNT for vertebral fracture using reference
populations from historical placebo-controlled trials, assuming an 86% relative
risk reduction in vertebral fracture with ABL treatment as observed in ACTIVE.
NNT was calculated as the reciprocal of the absolute risk reduction in ACTIVE.
The projected NNT for ABL in other populations was calculated based on incidence
rate (IR) for vertebral fractures in the placebo arms of the FREEDOM (placebo IR
7.2%), FIT-1 (placebo IR 15.0%), and FIT-2 (placebo IR 3.8%) trials. NNT for ABL
in ACTIVE was 28 for vertebral, 55 for nonvertebral, 37 for clinical, and 34 for
major osteoporotic fracture. NNT for these fracture types for teriparatide in
ACTIVE were 30, 92, 59, and 75, respectively. Using placebo IRs from FREEDOM, FIT
1, and FIT-2, projected NNTs for vertebral fracture with ABL were 17, 8, and 31.
These data are useful for further evaluating ABL for the treatment of
osteoporosis in postmenopausal women.
PMID- 29951743
TI - The Impact of Anthropogenic Disturbance on Bacterioplankton Communities During
the Construction of Donghu Tunnel (Wuhan, China).
AB - Bacterioplankton are both primary producers and primary consumers in aquatic
ecosystems, which were commonly investigated to reflect environmental changes,
evaluate primary productivity, and assess biogeochemical cycles. However, there
is relatively less understanding of their responses to anthropogenic disturbances
such as constructions of dams/tunnels/roads that may significantly affect the
aquatic ecosystem. To fill such gap, this study focused on the bacterioplankton
communities' diversity and turnover during a tunnel construction across an urban
lake (Lake Donghu, Wuhan, China), and five batches of samples were collected
within 2 months according to the tunnel construction progress. Results indicated
that both resources and predator factors contributed significant to the
variations of bacterioplankton communities, but the closed area and open areas
showed different diversity patterns due to the impacts of tunnel construction.
Briefly, the phytoplankton, TN, and TP in water were still significantly
correlated with the bacterioplankton composition and diversity like that in
normal conditions. Additionally, the organic matter, TN, and NH4-N in sediments
also showed clear effects on the bacterioplankton. However, the predator effects
on the bacterioplankton in the closed-off construction area mainly derived from
large zooplankton (i.e., cladocerans), while small zooplankton such as protozoa
and rotifers are only responsible for weak predator effects on the
bacterioplankton in the open areas. Further analysis about the ecological driving
forces indicated that the bacterioplankton communities' turnover during the
tunnel construction was mainly governed by the homogeneous selection due to
similar environments within the closed area or the open areas at two different
stages. This finding suggests that bacterioplankton communities can quickly adapt
to the environmental modifications resulting from tunnel construction activities.
This study can also give references to enhance our understanding on
bacterioplankton communities' response to ecological and environmental changes
due to intensification of construction and urbanization in and around lake
ecosystems.
PMID- 29951744
TI - A novel technique of reshaping the post of a constrained liner to avoid post and
primary box mismatch in a case of recurrent dislocation after total knee
arthroplasty.
AB - Knee dislocation after total knee arthroplasty, although rare, is a dangerous
injury that can lead to neurovascular compromise and permanent disability. With
the increase in number of total knee arthroplasty, more and more cases of
dislocations are being reported. We describe a novel technique of reshaping the
post of a constrained liner to fit into the box of a vanguard primary knee system
in a patient with recurrent posterior knee dislocation after a PS TKA with a
follow-up of 5 years.
PMID- 29951745
TI - The effect of flexion alignment in total hip arthroplasty with a cementless
tapered-wedge femoral stem.
AB - INTRODUCTION: The influence of stem sagittal alignment on clinical outcomes is
unclear in total hip arthroplasty (THA). The purpose of this study is to assess
the relationship between stem sagittal alignment and clinical and radiographic
outcomes using 3D-CT. MATERIALS AND METHODS: We performed 370 consecutive primary
THAs between 2009 and 2013. After exclusion, 102 hips in 89 patients using single
tapered-wedge stem were included. Mean follow-up was 4.7 years. Stem sagittal
alignment was measured using CT, and patients were divided into flexion and
neutral alignment groups. Clinical and radiographic outcomes were compared
between two groups. Furthermore, we evaluated the anterior femoral offset and
initial contact state. RESULTS: There were no significant differences in clinical
or radiographic outcomes between two groups. CT data analysis and multiple
regression analysis showed flexion alignment increased anterior femoral offset
(AFO) and Gruen zone 4 contact area. CONCLUSIONS: There was no significant
difference in clinical or radiographic outcomes between flexion and neutral
alignment of the tapered-wedge stem at an average of 4.7 years of follow-up. The
increase of AFO and distal contact area in flexion alignment could affect the
improvement of impingement-free range of flexion and intraoperative fracture.
PMID- 29951746
TI - Aging, non-communicable diseases, and old-age disability in low- and middle
income countries: a challenge for global health.
PMID- 29951747
TI - Protective effect of resveratrol on methylglyoxal-induced endothelial dysfunction
in aged rats.
AB - BACKGROUND: The cardiovascular benefits of resveratrol (RSV) have been well
established by previous experimental and clinical studies. The aim of this study
was to investigate the effectiveness of RSV administration on the impaired
endothelial function induced by methylglyoxal (MGO), and to elucidate the role of
endothelial nitric oxide synthase (eNOS) on its protective effect. METHODS: Aged
Wistar rats (80 weeks old, n = 15) were used in this study. The thoracic aorta
was isolated and cut into rings for organ culture. Aortic segments of rats were
incubated with MGO (420 uM) in the presence or absence of RSV (30 uM) for 4 h
(short-term) or 24 h (long-term). Isometric tension studies were performed by an
isolated organ bath in response to acetylcholine (ACh, an endothelium-dependent
vasodilator) and sodium nitroprusside (SNP, an endothelium-independent
vasodilator). Beside, expressions of eNOS and phospho-eNOS (p-eNOS) (Ser 1177) in
thoracic aorta rings were evaluated by immunohistochemistry. RESULTS: Both short
term and long-term MGO incubation significantly inhibited the relaxation response
induced by ACh, while the relaxation to SNP was not significantly altered. In
addition, eNOS and p-eNOS expressions decreased significantly in arteries
incubated with MGO. The impaired endothelial reactivity as well as decreased
expressions of eNOS and p-eNOS in MGO-incubated vessels were significantly
improved by RSV treatment. CONCLUSIONS: Endothelium-dependent vasodilatation of
the thoracic aorta was significantly inhibited by MGO administration, and RSV may
improve vascular endothelial function. The protective effect of RSV against MGO
induced endothelial dysfunction seems to be via increased eNOS expression and
activity.
PMID- 29951748
TI - The challenging management of a delayed union midshaft clavicle fracture
complicated by an acute pseudoaneurysm of the subclavian artery in a superelderly
diabetic patient.
PMID- 29951749
TI - [Reconstruction using the tensor fasciae latae muscle flap].
AB - OBJECTIVE: The tensor fasciae latae (TFL) muscle flap can be used for
reconstruction of decubital ulcers in the trochanteric or ischial region.
INDICATIONS: Deep decubital ulcers in the gluteal or ischial area after
debridement and exhaustion of conservative measures. CONTRAINDICATIONS: Moribund
or palliative patients who do not benefit from defect coverage and are likely to
suffer a life-threatening complication. Noncompliant patients who cannot follow
the postoperative recommendations or protocols in regard to positioning or
recurrence prevention. The presence of extensive scars after previous operations
in the donor area or irradiation of the donor area can lead to flap necrosis.
SURGICAL TECHNIQUE: The TFL flap is commonly used as a regional transposition
flap. Rare cases of a free TFL flap have been described. POSTOPERATIVE
MANAGEMENT: Following surgery the patient needs to be positioned on the side or
prone to prevent recurrence. Drains should be left for 5-7 days. Antibiotics are
only needed in the case of persistent florid infection. RESULTS: The TFL muscle
flap is known to be a reliable flap for the coverage of ulcers in the ischial and
trochanteric region following radical debridement. This flap can also be
transferred with its sensitive nerve supply resulting in a reduced chance of a
recurring ulcer.
PMID- 29951750
TI - A multifaceted individualized pneumoperitoneum strategy for laparoscopic
colorectal surgery: a multicenter observational feasibility study.
AB - BACKGROUND: While guidelines for laparoscopic abdominal surgery advise using the
lowest possible intra-abdominal pressure, commonly a standard pressure is used.
We evaluated the feasibility of a predefined multifaceted individualized
pneumoperitoneum strategy aiming at the lowest possible intra-abdominal pressure
during laparoscopic colorectal surgery. METHODS: Multicenter prospective study in
patients scheduled for laparoscopic colorectal surgery. The strategy consisted of
ventilation with low tidal volume, a modified lithotomy position, deep
neuromuscular blockade, pre-stretching of the abdominal wall, and individualized
intra-abdominal pressure titration; the effect was blindly evaluated by the
surgeon. The primary endpoint was the proportion of surgical procedures completed
at each individualized intra-abdominal pressure level. Secondary endpoints were
the respiratory system driving pressure, and the estimated volume of insufflated
CO2 gas needed to perform the surgical procedure. RESULTS: Ninety-two patients
were enrolled in the study. Fourteen cases were converted to open surgery for
reasons not related to the strategy. The intervention was feasible in all
patients and well-accepted by all surgeons. In 61 out of 78 patients (78%),
surgery was performed and completed at the lowest possible IAP, 8 mmHg. In 17
patients, IAP was raised up to 12 mmHg. The relationship between IAP and driving
pressure was almost linear. The mean estimated intra-abdominal CO2 volume at
which surgery was performed was 3.2 L. CONCLUSION: A multifaceted individualized
pneumoperitoneum strategy during laparoscopic colorectal surgery was feasible and
resulted in an adequate working space in most patients at lower intra-abdominal
pressure and lower respiratory driving pressure. ClinicalTrials.gov (Trial
Identifier: NCT03000465).
PMID- 29951752
TI - Human epidermal growth factor receptor 2-, epidermal growth factor receptor-, and
mesenchymal epithelial transition factor-positive sites of gastric cancer using
surgical samples.
AB - BACKGROUND: Receptor tyrosine kinases (RTKs) play critical roles in gastric
cancer (GC) progression and are potential targets for novel molecular-targeted
agents or photo-immunotherapies. During patient selection, targeted biopsy is the
first step. However, heterogeneous expression of RTKs based on the macroscopic
appearance in GC has not been extensively addressed. Accordingly, in this study,
we evaluated differences in RTK expression associated with macroscopic appearance
in GC. METHODS: In total, 375 consecutive patients who had undergone gastrectomy
at the National Cancer Center Hospital East and who had histologically proven
adenocarcinoma, available archived tumor sample, and no history of chemotherapy
were enrolled in this study. For these cases, tissue microarray (TMA) samples
were examined using immunohistochemistry (IHC). Based on the results of IHC,
cases were selected for detailed examination. We re-evaluated IHC scores in more
than three tumor blocks per case and comparatively evaluated differences in IHC
expression in RTKs between the mucosal portion (MuP) and invasive portion (InP).
RESULTS: Human epidermal growth factor receptor 2 (HER2)-, epidermal growth
factor receptor (EGFR)-, and mesenchymal epithelial transition factor (c-MET)
positive rates were 6, 9, and 20%, respectively. Twenty-two cases were then
analyzed to assess differences in IHC expression levels in the same lesion.
Concordance rates of positive staining of HER2, EGFR, and MET between MuP and
whole tumor were 100, 40, and 56% and those with InP were 46, 100, and 56%.
CONCLUSIONS: To avoid underestimating expression status, biopsies must be taken
from MuP for HER2, InP for EGFR, and both proportions for c-MET.
PMID- 29951753
TI - Quantifying insightful problem solving: a modified compound remote associates
paradigm using lexical priming to parametrically modulate different sources of
task difficulty.
AB - : Insight problem solving has been conceptualized as a dynamic search through a
constrained search space, where a non-obvious solution needs to be found.
Multiple sources of task difficulty have been defined that can keep the problem
solver from finding the right solution such as an overly large search space or
knowledge constraints requiring a change of the problem representation. Up to
now, there are very few accounts that focus on different aspects of difficulty
within an insight problem-solving context and how they affect task performance as
well as the probability of finding a solution that is accompanied by an Aha!
EXPERIENCE: In addition, we are not aware of any approaches investigating how
knowledge constraints parametrically modulate task performance and the Aha!
experience in compound remote associates (CRA) when controlling for other sources
of task difficulty. Therefore, we first developed, tested, and externally
validated a modified CRA paradigm in combination with lexical priming that is
more likely to elicit representational change than the classical CRA tasks.
Second, we parametrically estimated the effect of the knowledge constraint
together with other sources of difficulty (size of the problem and search space,
word length and frequency) using general linear mixed models. The knowledge
constraint (and the size of the search space) was operationalized as lexical
distance (measured as cosine distances) between different word pairs within this
task. Our results indicate that the experimentally induced knowledge constraint
still affects task performance and is negatively related to the Aha! experience
when controlling for various other types of task difficulties. Finally, we will
present the complete stimulus set in German language together with their
statistical (i.e., item difficulty and mean solution time) and lexical
properties.
PMID- 29951751
TI - Calcium channel gating.
AB - Tuned calcium entry through voltage-gated calcium channels is a key requirement
for many cellular functions. This is ensured by channel gates which open during
membrane depolarizations and seal the pore at rest. The gating process is
determined by distinct sub-processes: movement of voltage-sensing domains
(charged S4 segments) as well as opening and closure of S6 gates. Neutralization
of S4 charges revealed that pore opening of CaV1.2 is triggered by a "gate
releasing" movement of all four S4 segments with activation of IS4 (and IIIS4)
being a rate-limiting stage. Segment IS4 additionally plays a crucial role in
channel inactivation. Remarkably, S4 segments carrying only a single charged
residue efficiently participate in gating. However, the complete set of S4
charges is required for stabilization of the open state. Voltage clamp
fluorometry, the cryo-EM structure of a mammalian calcium channel, biophysical
and pharmacological studies, and mathematical simulations have all contributed to
a novel interpretation of the role of voltage sensors in channel opening,
closure, and inactivation. We illustrate the role of the different methodologies
in gating studies and discuss the key molecular events leading CaV channels to
open and to close.
PMID- 29951754
TI - Assessment of Three-Drug Combination Pharmacodynamic Interactions in Pancreatic
Cancer Cells.
AB - The pharmacodynamic interactions among trifluoperazine (TFP), gemcitabine (GEM),
and paclitaxel (PTX) were assessed in pancreatic cancer cells (PANC-1). The
phenothiazine TFP was chosen for its potential activity on cancer stem cells,
while GEM and PTX cause apoptosis. Effects of each drug alone and in various
combinations on cell growth inhibition of PANC-1 cells were studied in vitro to
determine the drug-specific parameters and assess the nature of drug
interactions. Joint inhibition (JI) and competitive inhibition (CI) equations
were applied with a psi interaction term. TFP fully inhibited growth of cells
(Imax = 1) with an IC50 = 9887 nM. Near-maximum inhibition was achieved for GEM
(Imax = 0.825) and PTX (Imax= 0.844) with an IC50 = 17.4 nM for GEM and IC50 =
7.08 nM for PTX. Estimates of an interaction term psi revealed that the
combination of TFP-GEM was apparently synergistic; close to additivity, the
combination TFP-PTX was antagonistic. The interaction of GEM-PTX was additive,
and TFP-GEM-PTX was synergistic but close to additive. The combination of TFP
IC60-GEM IC60-PTX IC60 seemed optimal in producing inhibition of PANC-1 cells
with an inhibitory effect of 82.1-90.2%. The addition of psi terms to traditional
interaction equations allows assessment of the degree of perturbation of assumed
mechanisms.
PMID- 29951755
TI - Acute toxicity and effects of Roundup Original(r) on pintado da Amazonia.
AB - The toxicity of Roundup Original(r) (GLY), a glyphosate-based herbicide widely
used in crops in Mato Grosso state, was determined in hybrid fish jundiara or
pintado da Amazonia. The 96 h-LC50 of GLY was 13.57 mg L-1. Moreover, exposure to
sublethal concentrations of GLY (0, 0.37, 0.75, 2.25, 4.5, 7.5 mg L-1) has not
altered the survival rate (100% for all treatments). In fish liver, protein
carbonyl (PC) levels as well as glutathione-S-transferase (GST) activity, reduced
glutathione (GSH), and ascorbic acid (ASA) contents increased when compared to
control group. Superoxide dismutase (SOD) activity was reduced and catalase (CAT)
has not changed. PC content has grown in muscle and brain, and thiobarbituric
acid-reactive species (TBARS) levels also increased in muscle, but in the brain,
they remained unaltered. Acetylcholinesterase (AChE) activity reduced in muscle
but increased in brain when compared to control group. Our results suggest that
short-term exposure to GLY induced alterations in the oxidative stress biomarkers
in fish and can be interfering with their survival in natural environment;
besides, these findings may be considered of high ecotoxicological relevance.
PMID- 29951756
TI - Glutamic acid assisted phyto-management of silver-contaminated soils through
sunflower; physiological and biochemical response.
AB - Phytoremediation is a cost-effective and eco-friendly technique for the removal
of heavy metal-contaminated soils and water. The less availability and mobility
of heavy metals in medium decreased the efficiency of this technique. The
mobility and availability of these metals in the medium can be enhanced by the
addition of organic chelators. The present study was conducted to investigate the
possibility of glutamic acid (GA) in improving silver (Ag) phytoextraction by
sunflower (Helianthus annuus L.). Different concentrations of Ag and GA were
supplied in solution form in different combinations after defined intervals.
Results depicted that increasing concentration of Ag significantly reduced the
plant biomass, photosynthetic pigments, and antioxidant enzyme activities (like
catalase, peroxidase, ascorbate, peroxidase, superoxide dismutase). Furthermore,
Ag stress increased the Ag concentration and the production of reactive oxygen
species (ROS) in sunflower plants. The addition of GA alleviated the Ag-induced
toxicity in plants and enhanced Ag concentration and accumulation in sunflower.
The addition of GA enhanced Ag accumulation in sunflower roots by 70, 79, 58, and
66% at 0-, 100-, 250-, and 500-MUM Ag treatments, respectively, as compared to
control plants. In conclusion, the results showed that Ag significantly reduced
the physiological and biochemical attributes in term of reduced growth of
sunflower and the addition of GA alleviated the Ag induced toxicity and enhanced
Ag uptake. The results suggested that sunflower can be used as hyper-accumulator
plant for the removal of Ag under GA. Further studies are required to understand
the role of GA at gene and microscopic level in plants.
PMID- 29951757
TI - M/g-C3N4 (M=Ag, Au, and Pd) composite: synthesis via sunlight photodeposition and
application towards the degradation of bisphenol A.
AB - In this work, natural sunlight successfully induced the deposition of gold (Au),
silver (Ag), and palladium (Pd) nanoparticles (NPs) with 17.10, 9.07, and 12.70
wt% onto the surface of graphitic carbon nitride (g-C3N4). The photocatalytic
evaluation was carried out by adopting Bisphenol A (BPA) as a pollutant under
natural sunlight irradiation. The presence of noble metals was confirmed by EDX,
HRTEM, and XPS analysis. The deposition of Ag NPs (7.9 nm) resulted in the
degradation rate which was 2.15-fold higher than pure g-C3N4 due to its
relatively small particle size, contributing to superior charge separation
efficiency. Au/g-C3N4 unveiled inferior photoactivity because the LSPR phenomenon
provided two pathways for electron transfer between Au NPs and g-C3N4 further
diminished the performance. The improved degradation lies crucially on the
particle size and Schottky barrier formation at the interface of M/g-C3N4 (M=Au,
Ag, and Pd) but not the visible light harvesting properties. The mechanism
insight revealed the holes (h+) and superoxide radical (*O2-) radical actively
involved in photocatalytic reaction for all composites.
PMID- 29951758
TI - A novel method for sewage sludge composting using bamboo charcoal as a separating
material.
AB - Traditional composting processes must be conducted with a bulking agent to ensure
adequate air space for aeration. The bulking agent and composting materials are
always completely mixed. A novel layered structure was introduced in sewage
sludge composting, in which no bulking agent was used and bamboo charcoal was
used as a separating material. Three lab-scale composting reactors (A: sawdust
and sludge; B: bamboo charcoal and sludge; and C: sawdust, bamboo charcoal, and
sludge) were continuously operated for 29 days. Several physicochemical
parameters were investigated to evaluate the feasibility of layered composting
with bamboo charcoal. The results indicated that the maximum temperatures during
the thermophilic stage in treatments A, B, and C were 51.4, 50.9, and 51 degrees
C, respectively. Layered composting with bamboo charcoal decreased the pH of the
thermophilic stage from 8.98 in A to 8.75 in C, and delayed the peaks by about
120 h. The degradation rates of dissolve organic carbon (DOC) and dissolved
nitrogen (DN) were 75 and 71.5% in treatment B, respectively, which were
significantly higher than those of control group A (60 and 59.1%, respectively).
The total NH3 emissions of treatment C (2127.8 mg) were significantly lower than
those of A (2522.8 mg). Our results suggested that layered composting using
bamboo charcoal as a separating material could be an alternative strategy to the
traditional composting method. Moreover, layered composting combined with sawdust
could effectively reduce NH3 emissions and N loss.
PMID- 29951759
TI - Kinetics and thermodynamics of urea hydrolysis under the coupling of nitrogen
application rate and temperature.
AB - This study aimed to determine the coupled effects of temperature and urea
application rate on kinetic and thermodynamic parameters to supplement the
mechanism of urea hydrolysis and modify the Arrhenius model to improve the
prediction accuracy of urea content. Laboratory experiments were conducted for
sandy loam soil under different temperatures (T) (288, 293, 298, and 308 K) and
urea application rates (F) (247, 309, 371, and 433 mg kg-1). Urea content was
determined daily through high-performance liquid chromatography. Results showed
that the interaction between temperature and urea application rate had a
significant effect on reaction rate (Ku) and half-life (H1/2), whereas no
significant effect on activation degree (lgN), activation free energy (DeltaG),
activation enthalpy (DeltaH), and activation entropy (DeltaS). The new Ku(T)-2
model with a determination coefficient (R2) = 0.990 was more accurate than the
Arrhenius model with R2 = 0.965. The new U(T, F) model with a mean absolute
percentage error (MAPE) = 3.62% was more accurate than the traditional U(T) model
with a MAPE = 6.38%. The effects of T and F were observed mainly during the
preparatory stage and the most critical transition stage of the chemical
reaction, respectively. The findings DeltaH > 0, DeltaG > 0, and DeltaS < 0
indicated that urea hydrolysis was endothermic and controlled by enthalpy. These
results supplemented the mechanism of urea hydrolysis and improved the prediction
accuracy of urea content.
PMID- 29951761
TI - Potential health impacts from different vegetable nitrate intake scenarios and
providing strategies to manage the risks for Iranian population.
AB - Health risk from nitrate was predicted for different scenarios of vegetable
consumption and nitrate contents in Iran. Finally, certain management scenarios
were presented for nitrate risk mitigation under worst-case scenario considering
each vegetable contribution in nitrate intake. Two fruit (bell pepper and tomato)
and two leafy vegetables (lettuce and mint) were sampled in a combined randomized
method from fields, greenhouses, and markets of Isfahan province, Iran during
October to December 2015. To assess the potential health impacts of nitrate from
the vegetable ingestion, the present status and three different scenarios of
increasing vegetable consumption and/or increasing plant nitrate concentrations
were considered. Two management scenarios for reducing the total nitrate intake
below the allowable values were predicted. By increasing vegetable consumption
under scenario 1 and nitrate concentration under scenario 3, the total hazard
quotient (THQs) was increased, although the highest increase (12-fold) in the
THQs was provided by lettuce. Health risk from nitrate for sensitive groups was
effectively reduced by a 70% decrease in lettuce nitrate concentration. In the
second management scenario, decreasing upper nitrate concentrations in the other
sources (except lettuce) by 30% declined nitrate intake in children (< 6 years
old) and boys (7-14 years old) below acceptable daily intake (ADI). By taking
into account the increases in the amounts of consumption and nitrate in
vegetables at different scenarios, it was revealed that the critical factor for a
high dietary exposure to nitrate is not the absolute amount of vegetables
consumed but the type of vegetable (lettuce) and the concentration of nitrate
related to the conditions of production. Therefore, to manage any risks to human
health from dietary nitrate exposure resulting from vegetable consumption, focus
on lettuce instead of taking other vegetables equally into account is needed.
PMID- 29951760
TI - Bacterial microbiome of root-associated endophytes of Salicornia europaea in
correspondence to different levels of salinity.
AB - The halophytes have evolved several strategies to survive in saline environments;
however, an additional support from their associated microbiota helps combat
adverse conditions. Hence, our driving interests to investigate the endophytic
bacterial community richness, diversity, and composition associated to roots of
Salicornia europaea from two test sites with different origins of soil salinity.
We assumed that salinity will have a negative effect on the diversity of
endophytes but simultaneously will permit the high occurrence of halophylic
bacteria. Further, to establish the role of the host and its external environment
in determining the endophytic diversity, we analyzed the physico-chemical
parameters of root zone soil and the concentration of salt ions in the plant
roots. The results based on the Miseq Illumina sequencing approach revealed a
higher number of endophytic bacterial OTUs at naturally saline test site with a
higher level of soil salinity. Proteobacteria and Bacteriodetes were the dominant
endophytic phyla at both analyzed sites; additionally, the high occurrence of
Planctomycetes and Acidobacteria at more saline site and the occurrence of
Firmicutes, Actinobacteria, and Chloroflexi at less saline site were recorded.
The salinity in the root zone soil was crucial in structuring the endophytic
community of S. europaea, and the significant prevalence of representatives from
the phyla Deltaproteobacteria, Acidobacteria, Caldithrix, Fibrobacteres, and
Verrucomicrobia at the more saline test site suggest domination of halophylic
bacteria with potential role in mitigation of salt stress of halophytes.
PMID- 29951762
TI - Source apportionment of heavy metals and their ecological risk in a tropical
river basin system.
AB - Surface water and sediment samples were collected from Ajay River basin to
appraise the behavior of heavy metals with surrounding environments and their
inter-elemental relationships. Parameters like pH and organic carbon are having a
minimal role in heavy metal distribution while some elements like Fe and Cu
showed great affinity for organic matter based on linear regression analysis
(LRA). Ficklin diagram justified that river basin is not contaminated through
acidic pollutants. The river basin is highly enriched with Cu, Cd, Pb, and Ni
which were much higher than world average values, average shale standard, effect
range low (ERL), and threshold effect level (TEL). PCA and LRA verified that Cu,
Cd, Pb, and Ni were mainly derived from anthropogenic inputs, and others like Fe,
Mn, Zn, and Co came from geogenic sources. Pollution indices revealed that river
basin is moderately to highly contaminated by Cu, Cd, and Ni. Furthermore, Ajay
River basin is under strong potential ecological risk based on the obtained value
of risk index and probable effect level/effect range median quotient index.
However, river basin is strongly influenced by lithological properties,
diversified hydrogeological settings, mineralization and mobilization of
subsurface materials, and urban and industrial effluents which are controlling
the heavy metals.
PMID- 29951764
TI - Properties and effects of organic additives on performance and emission
characteristics of diesel engine: a comprehensive review.
AB - Fast depletion of conventional automobile fuels and environmental pollution due
to exhaust emission are the issues of great importance. Improvement in engine
performance and emission control is quite difficult to handle simultaneously. The
fuel properties can be improved substantially by incorporation of additives in
different proportions to get better emission standard without deteriorating the
engine performance. The aim of current study is to review/summarize the effects
of various organic additives on the engine performance (i.e., brake thermal
efficiency, brake specific fuel consumption, volumetric efficiency, etc.) and
emissions (i.e., carbon dioxide, carbon monoxide, nitrogen oxides, hydrocarbons,
particulate matter, and other harmful compounds). The physico-chemical and
combustion properties (i.e., density, latent heat, dynamic viscosity, flash
point, boiling point, cetane number, oxygen content, lower heating value, auto
ignition temperature, etc.) of various additives were also discussed to check the
suitability of additives with diesel. Finally, limitations and opportunities
using organic additives with respect to engine performance and combustion were
discussed to guide future research and improvement in this field.
PMID- 29951763
TI - Solvent effect on endosulfan adsorption onto polymeric arginine-methacrylate
cryogels.
AB - Endosulfan is a persistent insecticide that is still used in some countries even
though it is life-threatening and banned in the agricultural struggle. The
solubility of pesticides in water is negligible. It is known that pesticides with
better solubility in organic solvents have different solubility when the
dielectric constants of these solvents are taken into account. The polymeric
structure of arginine was modified with methacrylate to be a functional monomer,
and it was immobilized on a solid support, poly(HEMA), and finally, poly(2
hydroxyethyl methacrylate-arginine methacrylate) was obtained and used as an
effective adsorbent. The effect of organic solvents on endosulfan adsorption was
investigated for the first time in the literature. Endosulfan was removed from
alcohol media by using this polymeric structure synthesized by exploiting alcoho
phobic interaction in this work. Nuclear magnetic resonance (NMR), elemental
analysis, and Fourier transform infrared spectroscopy (FTIR) methods were used
for the structural characterization and therefore to prove successful synthesis
of cryogels. Morphological characteristics were also investigated by scanning
electron microscopy (SEM), an N2 adsorption method, and swelling test. Adsorption
experiments were carried out against varying interaction time and concentration
parameters in the batch system. Since the alcohol used as a solvent has a pH
value close to the ionic strength of drinking water, no change was made in the pH
of the solution. Endosulfan molecules dissolved in solvents such as toluene,
dichloromethane, acetone, and chloroform were removed using poly(HEMA-ArMA)
cryogels to determine the solvent effect on the adsorption of endosulfan. As
expected, the removal of endosulfan from the solvent toluene provided the best
result. Although the adsorption in toluene is almost 9.5 times higher than that
in ethanol, the use of toluene in the adsorption process due to its chemical
structure is not feasible. Thus, experiments were carried out in ethanol.
PMID- 29951765
TI - Chiral triazole fungicide tebuconazole: enantioselective bioaccumulation,
bioactivity, acute toxicity, and dissipation in soils.
AB - Enantioselectivity in environmental behavior and toxic effect of chiral
pesticides has been received much attention. In this study, enantioselective
bioactivity towards target organism Botrytis cinerea, acute toxicity and
bioaccumulation in Eisenia fetida, and degradation in five kinds of soil under
laboratory conditions regarding triazole fungicide tebuconazole were
investigated. The results showed that fungicidal activity to Botrytis cinerea of
R-(-)-tebuconazole was 44 times higher than S-(+)-tebuconazole with an order of R
(-)-tebuconazole > rac-tebuconazole > S-(+)-tebuconazole. No significant
difference was found in acute toxicity of rac-, R-, and S-tebuconazole to E.
fetida with 48-h EC50 of 10.78, 10.48, and 10.84 MUg/cm2, respectively.
Dissipation of tebuconazole in the five tested soils varied upon soil
characteristics with half-life ranging from 32.2 to 216.6 days. Enantioselective
and rapid dissipation of tebuconazole were observed in soils Hainan and
Huajiachi, compared to the other soils. Enantioselective accumulation of
tebuconazole in E. fetida was found with a preferential of S-(+)-tebuconazole
although no significant difference in acute toxicity to E. fetida between rac
tebuconazole and enantiomers. The results indicated that S-(+)-tebuconazole with
less fungicidal activity may be more likely to be accumulated in earthworm E.
fetida. This research is helpful to better evaluate the environmental and
ecological risk of tebuconazole on enantiomeric level.
PMID- 29951766
TI - Increased leaching and addition of amendments improve the properties of seawater
neutralized bauxite residue as a growth medium.
AB - Laboratory and greenhouse experiments were carried out to investigate the
chemical, physical, and microbial properties of seawater-neutralized bauxite
residues and the effects of additional leaching (1 pore volume of deionized water
versus an additional 6 pore volumes) and amendment with gypsum (5%) and/or cattle
manure (6%) on its properties and on the growth of Rhodes grass (Chloris gayana).
Additional leaching resulted in a decrease in EC, exchangeable Na, SAR, and ESP.
For unamended control treatments, additional leaching induced a rise in pHSE from
8.5 to 9.6 and pH1:5 from 9.1 to 10.1 due to dissolution of residual alkalinity.
Addition of gypsum arrested this pH increase resulting in a final pHSE of 7.5 and
pH1:5 of 8.8. In control treatments, additional leaching resulted in a pronounced
decrease in Rhodes grass yields. However, in gypsum and cattle manure-amended
treatments, it led to substantial yield increases and decreases in tissue Al and
Na concentrations and increased K/Na ratios. Upon drying for the first time,
bauxite residue was shown to contract and form a solid massive structure. The
aggregates formed from crushing this material were water stable (as measured by
wet sieving). Additions of cattle manure or gypsum to residue aggregates did not
affect pore size distribution. Addition of cattle manure increased organic C and
microbial biomass C content and basal respiration rate while additional leaching
increased basal respiration and metabolic quotient. It was concluded that a
combination of drying and crushing the residue, amending it with gypsum and
organic manure followed by extensive leaching results in the formation of a
medium that supports plant growth.
PMID- 29951767
TI - Evaluation of heterogeneous catalytic ozonation process for diclofenac
degradation in solutions synthetically prepared.
AB - Sodium diclofenac (DCF) is a common analgesic and anti-inflammatory drug, which
has become an environmental problem due to its growth and accumulation into water
bodies. In this work, commercial (with excipients) and analytical (pure) DCF
mineralization was studied by means of heterogeneous catalytic ozonation. The
process was carried out with magnetite (Fe3O4) as a catalyst, which preserves its
physical and chemical properties during the process. The best results of
mineralization were obtained after a 40-min treatment of 35 mg/L analytical DCF
solution, with a 0.5 g/L catalyst concentration. These results showed the highest
organic load decrease, measured as dissolved organic carbon (DOC) and chemical
oxygen demand (COD), with 94 and 89%, respectively. In addition, the percentage
of organic load decrease was compared between the conventional and the catalyzed
process. Besides, reaction products were identified by gas chromatography-mass
spectrometry (GC-MS) and the catalytic properties were identified by Mossbauer
spectroscopy, which showed the catalyst maintained its nature after the process.
Finally, the results obtained show that the heterogeneous catalytic process could
be an efficient degradation treatment for emerging contaminants such as DCF.
PMID- 29951768
TI - Acute cocoa flavanols intake improves cerebral hemodynamics while maintaining
brain activity and cognitive performance in moderate hypoxia.
AB - INTRODUCTION: Acute cocoa flavanols (CF) intake has been suggested to modulate
cognitive function and neurovascular coupling (NVC). Whether increased NVC is
solely driven by improved vascular responsiveness or also by neuronal activity
remains unknown. This study investigated the effects of acute CF intake on
cognitive performance, NVC, and neuronal activity in healthy subjects in normoxia
and hypoxia (4000 m simulated altitude; 12.7% O2). METHODS: Twenty healthy
subjects (age 23.2 +/- 4.3 years) performed four trials. Participants performed a
Stroop task and "cognition" battery 2 h after acute CF (530 mg CF, 100 mg
epicatechin) or placebo intake, and 30 min after initial exposure to hypoxia or
normoxia. Electroencephalogram and functional near-infrared spectroscopy were
used to analyze hemodynamic changes and neuronal activity. RESULTS: CF enhanced
NVC in the right prefrontal cortex during several tasks (risk decision making,
visual tracking, complex scanning, spatial orientation), while neuronal activity
was not affected. CF improved abstract thinking in normoxia, but not in hypoxia
and did not improve other cognitive performances. Hypoxia decreased accuracy on
the Stroop task, but performance on other cognitive tasks was preserved. NVC and
neuronal activity during cognitive tasks were similar in hypoxia vs. normoxia,
with the exception of increased beta activity in the primary motor cortex during
abstract thinking. CONCLUSIONS: Acute CF intake improved NVC, but did not affect
neuronal activity and cognitive performance in both normoxia and hypoxia. Most
cognitive functions, as well as NVC and neuronal activity, did not decline by
acute exposure to moderate hypoxia in healthy subjects.
PMID- 29951770
TI - High-throughput and sensitive determination of urinary zearalenone and
metabolites by UPLC-MS/MS and its application to a human exposure study.
AB - Biomarker-based strategies to assess human exposure to mycotoxins have gained
increased acceptance in recent years. In this study, an improved method based on
UPLC-MS/MS following 96-well MUElution solid-phase extraction was developed and
validated for the sensitive and high-throughput determination of zearalenone
(ZEN) and its five metabolites alpha-zearalenol (alpha-ZEL), beta-zearalenol
(beta-ZEL), alpha-zearalanol (alpha-ZAL), beta-zearalanol (beta-ZAL), and
zearalanone (ZAN) in human urine samples, using 13C-ZEN as an internal standard
for accurate quantification. Two plates of samples (n = 192) could be processed
within 2 h, and baseline separation of all the analytes was achieved in a total
runtime of 6 min. The proposed method allowed ZEN and its metabolites to be
sensitively determined in a high-throughput way for the first time, and with
significantly improved efficiency and accuracy with respect to existing methods.
The limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.02
to 0.06 ng mL-1 and from 0.05 to 0.2 ng mL-1, respectively. The recoveries for
the spiked samples were from 87.9 to 100%, with relative standard deviations
(RSDs) of less than 7%. 301 urine samples collected from healthy volunteers aged
0-84 years in China were analyzed with and without enzyme hydrolysis to determine
total and free ZEN biomarkers, respectively. ZEN, ZAN, alpha-ZEL, and beta-ZEL
were detected in 71.4% of the samples at levels of 0.02-3.7 ng mL-1 after enzyme
hydrolysis. The estimated mean probable daily intake (PDI) was much lower than
the tolerable daily intake (TDI). Adolescents had higher exposure than children,
adults, and the elderly. Graphical abstract ?.
PMID- 29951769
TI - Acute tramadol enhances brain activity associated with reward anticipation in the
nucleus accumbens.
AB - BACKGROUND: Tramadol is an analgesic with monoamine reuptake inhibition and MU
opioid receptor activation. Although tramadol has been widely used for treatment
of various pain conditions, there is controversy over the risk of abuse
potential. We examined the effects of tramadol on the reward system in humans
using functional magnetic resonance imaging (fMRI) to assess the potential of
tramadol for drug abuse or dependence. METHODS: A randomized, double-blind,
placebo-controlled, crossover study was conducted for 19 healthy adults under
tramadol or placebo. In association with subjective mood questionnaires, monetary
incentive delay (MID) task was performed to assess the neural response to reward
anticipation during fMRI. Subjective mood measures and blood oxygenation level
dependent (BOLD) signal during gain and loss anticipation were compared between
tramadol and placebo. RESULTS: Tramadol significantly reduced anxiety (Z = -
2.513, p = 0.012) and enhanced vigor (Z = - 2.725, p = 0.006) compared with
placebo. By Mood Rating Scale, tramadol provoked contented (Z = - 2.316, p =
0.021), relaxed (Z = - 2.236, p = 0.025), and amicable feelings (Z = - 2.015, p =
0.044) as well as increased alertness (Z = - 1.972, p = 0.049) and contentedness
domains (Z = - 2.174, p = 0.030) compared with placebo. Several brain regions
including nucleus accumbens (NAc) were activated during gain anticipation in the
MID task under both tramadol and placebo. Tramadol increased the %BOLD signal
change in NAc at +Y500 cue significantly more than the placebo (Z = - 2.295, p =
0.022). CONCLUSION: Tramadol enhances the reward system and thereby may have
abuse potential or precipitate drug abuse in human.
PMID- 29951771
TI - Hits and misses in research trends to monitor contaminants in foods.
AB - Monitoring of chemicals of toxicological concern in food is commonly needed for
many purposes, which include (in part) food safety, regulatory enforcement, risk
assessment, international food trade, label claims, environmental protection,
industry needs, academic research, and consumer confidence. Chemicals of current
concern include a variety of toxins, pesticides, veterinary drugs, growth
promoters, environmental contaminants, toxic metals, allergens, endocrine
disruptors, genetically modified organisms, melamine, acrylamide, furans,
nitrosamines, food additives, packaging components, and miscellaneous other
chemicals. In light of past crises, the potential harm from known or unknown
chemicals not currently monitored are a source of additional concern by the food
industry, regulators, scientists, and consumers. As global food trade has
expanded and detection techniques have improved, chemical contaminant analysis of
foods has also increased in importance and activity. This critical review article
is aimed to highlight current trends in the literature, including neglected
research needs, on the analysis of chemicals of toxicological concern in foods.
Graphical abstract.
PMID- 29951772
TI - Ionic liquid inspired alkalinochromic salts based on Reichardt's dyes for the
solution phase and vapochromic detection of amines.
AB - Chromogenic salts based on the negatively solvatochromic pyridinium N-phenolate
betaines 2,6-diphenyl-4-(2,4,6-triphenyl-N-pyridino)-phenolate (Reichardt's dye
30) and 2,6-dichloro-4-(2,4,6-triphenyl-N-pyridino)-phenolate (Reichardt's dye
33) proved to be promising probes for the colorimetric detection of bases,
including hydroxide ion, ammonia, and aliphatic amines. Specifically, the
protonated halide forms of these two dyes were ion exchanged to generate
lipophilic bis(trifluoromethylsulfonyl)imide derivatives, denoted [ET(30)][Tf2N]
and [ET(33)][Tf2N], respectively. When dissolved in 95 vol% EtOH, these
essentially colorless solutions displayed dramatic "alkalinochromic" color-on
switching due to phenolic deprotonation to generate the zwitterionic form of the
dyes with their characteristic charge-transfer absorption. The extent of the
colorimetric response varied with the base strength for the aliphatic amines
tested (i.e., propylamine, ethanolamine, ethylenediamine, diethylenetriamine,
triethylamine, triethanolamine), being loosely correlated with the pKb of the
amine. In addition, we demonstrated proof of concept for the vapochromic
detection of ammonia and aliphatic amines by dissolution of the chromogenic
probes in the ionic liquid 1-propyl-1-methylpyrrolidinium
bis(trifluoromethylsulfonyl)imide. We also showed that the dyed ionic liquid can
be successfully immobilized within silica sol-gel ionogels to generate more
practical and robust sensory platforms. This strategy represents a useful
addition to existing colorimetric sensor arrays targeting amines and other basic
species. In particular, the differential response of the two different probes
offers a measure of chemical selectivity which will be of interest for detecting
biogenic amines in food safety applications, among other areas.
PMID- 29951773
TI - Analyte and matrix evaporability - key players of low-temperature plasma
ionization for ambient mass spectrometry.
AB - The introduction of ambient ionization at atmospheric pressure for mass
spectrometry (AI-MS) attracted the interest of many researchers in the field and
various ionization techniques have been described in recent years that allow a
quick and easy-to-handle analysis of samples under ambient conditions without or
with only minor sample preparation. Among those, plasma-based techniques
including the low-temperature plasma probe require very little resources thereby
providing great potential for implementation in mobile analytical devices.
However, systematic studies on signal responsiveness with this technique, such as
the influence of the analyte and matrix characteristics on relative signal
intensity, are still rare. Therefore, we used a low-temperature plasma source
based on dielectric barrier discharge with helium as process gas to assess
influencing factors on signal intensity in mass spectrometry. Among 12 tested
molecular descriptors, in particular a low vaporization enthalpy and a large
molecular nonpolar surface area improve the relative signal intensity. In
addition, we show that the impact of compound characteristics strongly
outperforms the influence of simple sample matrices such as different organic
solvents and water, with a weak trend that volatile solvents tend to decrease the
signal responsiveness of the analytes. However, several specific solvent-analyte
interactions occurred, which have to be considered in targeted applications of
this method. Our results will help further in improving the implementation and
standardization of low-temperature plasma ionization for ambient mass
spectrometry and understanding the requirements and selectivity of this
technique. Graphical abstract Influencing factors (analyte and matrix
characteristics) on signal intensity in dielectric-barrier discharge plasma for
ionization in mass spectrometry.
PMID- 29951775
TI - Food and Nutrient Intakes of Jamaican Immigrants in Florida.
AB - This study assessed dietary intakes, nutritional composition, and identified
commonly eaten foods among Jamaicans in Florida. Dietary intake was assessed
among 44 study participants to determine commonly eaten foods and nutrient
composition. Weighed recipes were collected and analyzed to determine nutrient
composition for traditional foods. Top foods that contributed to macronutrient
and micronutrient intake were identified and adherence to dietary recommendations
was evaluated. Mean daily energy intake was 2879 (SD 1179) kcal and 2242 (SD
1236) kcal for men and women respectively. Mean macronutrient intakes were above
dietary recommendations for men and women. Top foods contributing to energy
included rice and peas, sweetened juices, chicken, red peas soup, and hot
chocolate drink. Results showed sodium intake was more than double the adequate
intake estimate (1300-1500 mg). Findings highlight the need to include commonly
eaten traditional foods in dietary questionnaires to accurately assess diet
related chronic disease risk. Findings have implications for risk factor
intervention and prevention efforts among Jamaicans.
PMID- 29951774
TI - Expression and Metabolomic Profiling in Axial Spondyloarthritis.
AB - PURPOSE OF REVIEW: The purpose of this review is to highlight recent evidence
with respect to expression and metabolomic profiling in axial spondyloarthritis
(axSpA) that included ankylosing spondylitis (AS). RECENT FINDINGS: AxSpA is not
only characterized by the strongest genetic contribution for any complex
rheumatic disease but is also influenced by environmental and immunological
factors. Large-scale association-based studies have identified over 100 genetic
variants contributing to 30% of the genetic risk of ankylosing spondylitis.
Recent studies in global expression and metabolomic profiling appear to highlight
common themes despite differences in tissues, populations, techniques, and
relative paucity of patients in many of these studies. Expression studies support
a role for immunomodulation and bone remodeling in the pathogenesis and
progression of axSpA/AS, while metabolomic studies implicate the importance of
the intestinal microbial metabolism as well as fat and choline metabolic pathways
in AS.
PMID- 29951777
TI - Differences in femoral morphology among the Orientals and Caucasians: a
comparative study using plain radiographs.
AB - The purpose of this study was to identify the differences in femoral dimensions
among Caucasian and Oriental populations. A total of 268 femora were collected
from China, Japan, Korea, Taiwan and the United States. Firstly, the dimensional
parameters for measuring femur were identified. These were initially measured on
bone specimens to determine the methodology, followed by measuring the same
parameter on plane radiographs of the same bone specimen using a board, and
digitized with the aim of verifying the repeatability and reliability of the
data. Data were analyzed using ANOVA, paired students t test and Pearson's
correlation analysis. The results revealed that Caucasian femora are
significantly larger in maximum bone length (BL), head-neck length (HNL), lesser
trochanter width and the total width of the distal epiphysis (Wdf). The Beijing
femora were found to be the longest and the Japanese femora constituted the
shortest bone lengths and smallest angle alpha among the Oriental populations. A
strong correlation was observed between Wdf and HD, HNL, Wmc and Wlc in all the
populations; however, correlation between Wdf and BL was mild. The angle alpha
showed no correlation with BL. This study generated a large database of femoral
geometry, which may help pharmaceutical companies to design orthopedic implants
for Oriental populations.
PMID- 29951776
TI - Histone deacetylase 1 expression is inversely correlated with age in the short
lived fish Nothobranchius furzeri.
AB - Aging is associated with profound changes in the epigenome, resulting in
alterations of gene expression, epigenetic landscape, and genome architecture.
Class I Histone deacetylases (HDACs), consisting of HDAC1, HDAC2, HDAC3, and
HDAC8, play a major role in epigenetic regulation of chromatin structure and
transcriptional control, and have been implicated as key players in the
pathogenesis of age-dependent diseases and disorders affecting health and
longevity. Here, we report the identification of class I Hdac orthologs and their
detailed spatio-temporal expression profile in the short-lived fish
Nothobranchius furzeri from the onset of embryogenesis until old age covering the
entire lifespan of the organism. Database search of the recently annotated N.
furzeri genomes retrieved four distinct genes: two copies of hdac1 and one copy
of each hdac3 and hdac8. However, no hdac2 ortholog could be identified.
Phylogenetic analysis grouped the individual killifish class I Hdacs within the
well-defined terminal clades. We find that upon aging, Hdac1 is significantly
down-regulated in muscle, liver, and brain, and this age-dependent down
regulation in brain clearly correlates with increased mRNA levels of the cyclin
dependent kinase inhibitor cdkn1a (p21). Furthermore, this apparent reduction of
class I HDACs in transcript and protein levels is mirrored in the mouse brain,
highlighting an evolutionarily conserved role of class I HDACs during normal
development and in the aging process.
PMID- 29951779
TI - Grape polyphenols corrects ageing-related detriments in neutrophil functionality
via modulation of specific molecular targets.
AB - Oxidative stress and inflammation are intricately interlinked as aetiological
factors in the context of ageing and chronic disease-related accelerated ageing.
Previous research by our group has highlighted the anti-oxidant and anti
inflammatory potential of grape-derived polyphenols in the context of acute
inflammation and oxidative stress. The aim here was to add to this by assessing
efficacy of the treatment (acutely) to address ageing-associated cumulative pro
oxidant and pro-inflammatory changes in an in vitro model. Blood from young and
aged humans was analysed for baseline oxidative stress and inflammatory status.
Isolated neutrophils were acutely exposed to the polyphenol treatment in vitro.
The chemokinetic capacity of treated and control neutrophils in response to fMLP
was subsequently determined in a Dunn chamber, using live cell imaging.
Neutrophils were also analysed for the expression of selected molecular markers
associated with functional capacity and oxidative stress. Results indicate that
the aged population had significantly worse oxidative stress and inflammatory
profiles (higher plasma conjugated dienes and MPO) than young controls.
Neutrophils isolated from both young and aged individuals had improved
chemokinetic accuracy and capacity after in vitro polyphenol treatment.
Additionally, increased shedding of CD16 and expression of CD66b suggested sites
via which the polyphenol achieved improved neutrophil motility. We conclude that
grape seed-derived polyphenols facilitated improved neutrophil functionality by
acting on the molecular targets elucidated here.
PMID- 29951778
TI - Respiratory health of dust-exposed Congolese coltan miners.
AB - PURPOSE: In Democratic Republic of the Congo (DRC), informal coltan mining has
been expanding amidst increased insecurity due to armed conflicts. We
investigated the impact of occupational dust-exposure on the respiratory health
of Congolese coltan miners. METHODS: In total, 441 Congolese workers participated
in this study, including 199 informal coltan miners and 242 office workers
(controls). Information on respiratory complaints was collected using two
standardized questionnaires. Physical examination (vital signs, auscultation) and
lung function test (Peak Flow meter) were performed. In addition, workplace
airborne PM2.5 and volatile organic compounds (VOC) concentrations were measured.
RESULTS: Higher airborne PM2.5 (range 180-210 ug/m3) and VOC (range 1.4-2.3
ug/m3) levels were detected at coltan mining work stations as compared with
control sites (19-44 and 0.5-0.8 ug/m3, respectively). All respiratory complaints
and disorders were more prevalent in informal coltan miners than in controls.
Additionally, a markedly lower mean PEFR was observed in coltan miners than in
controls (347.93 +/- 6.88 vs. 493.23 +/- 67.38 L/min, respectively). Moreover,
positive associations between informal coltan mining and almost all respiratory
complaints were observed, except wheezing at effort and night cough. On the other
hand, an inverse association was observed between lung function (PEFR) and PM2.5
exposure, between PEFR and VOC exposure, and also between PEFR and current
smoking. CONCLUSIONS: This study showed high prevalence of respiratory complaints
in Congolese informal coltan miners, suggesting the necessity to implement
efficient occupational safety measures and regulate this informal mining
business.
PMID- 29951780
TI - Sleep Dysfunction and Behavioral Daytime Problems in Children with Autism
Spectrum Disorders: A Comparative Study.
AB - OBJECTIVES: To compare parent reported sleep behaviors of children with Autism
Spectrum Disorders (ASD) and normal healthy controls and to examine the
association of sleep disturbances with daytime behavioral difficulties in
children with ASD. METHODS: Sixty ASD children (85% boys) (Mean age=6.1 y,
SD=2.4) were recruited from the Psychology unit of the Department of Pediatrics
of a tertiary care hospital. An age and socio-economic status matched group of
typically developing (TD) children (N=60) were also recruited. The Children's
Sleep Habits Questionnaire (CSHQ) was used to measure sleep problems. The
Childhood Psychopathology Measurement Schedule was used to measure day time
behavioral difficulties. RESULTS: Sleep problems were nearly two times more
prevalent among children with ASD (88.3%) as compared to the TD group (46.7%)
(chi2=23.74, P=0.0001). The total CSHQ and 6 out of the 8 subscales scores of the
ASD group were also significantly higher than the TD group. Overall, children
with ASD displayed significant more bedtime resistance than controls (t= 3.95,
P=0.001). The sleep duration subscale showed that children with ASD, relative to
the TD group, slept too little (chi2=23.08, P=0.0001), did not sleep the right
amount of time (chi2= 11.86, P=0.003), and displayed significant variation in the
duration of time slept (chi2=11.96, P=0.003). In addition, parent reported sleep
dysfunction had a significant relationship with daytime reported behavior
difficulties (r=0.53, P=0.01) in children with ASD. Stepwise multiple regression
analysis revealed that 30% of the variance in number of daytime behavioral
problems was explained by only two variables: total CSHQ scores and duration of
night awake time (F=11.18, P=0.001). CONCLUSIONS: Children with ASD are at a high
risk for sleep problems and this is associated with daytime behavior
disturbances. Pediatricians should routinely screen ASD children for sleep
problems and initiate timely and appropriate interventions.
PMID- 29951781
TI - Impact of Pediatric Malignancies on Parent's Quality of Life.
PMID- 29951782
TI - Concomitant Ventral Hernia Repair and Bariatric Surgery: a Systematic Review.
AB - This study is a review on the management of ventral hernia during bariatric
surgery. The main outcomes are the recurrence rate after ventral hernia repair
and the incidence of prosthetic infection. Eleven studies were included. Ventral
hernias were treated by simple suture (n = 191), synthetic mesh (n = 186), and
biological mesh (n = 72). Mean defect size was 18 cm2. Recurrence rate was 25.7%
in the suture group, 14.3% in the biomesh group, and 1.1% in the synthetic mesh
group (p < 0.05). Mesh infection rate was not different between the groups. No
significant difference was observed in 30-day reoperation. Concomitant treatment
of small hernia defect is feasible and safe during bariatric surgery. Synthetic
mesh provides a significantly lower recurrence rate without any increase in 30
day wound morbidity.
PMID- 29951783
TI - Reply to Letter to Editor: Comment on "Improvement of Body Composition and
Quality of Life Following Intragastric Balloon".
PMID- 29951784
TI - Laparoscopic Greater Curvature Plication and Laparoscopic Sleeve Gastrectomy
Treatments for Obesity: Systematic Review and Meta-Analysis of Short- and Mid
Term Results.
AB - BACKGROUND: Laparoscopic greater curvature plication (LGP) has recently emerged
as a new bariatric procedure. This surgery provides gastric restriction without
resection, which could potentially provide a lower risk alternative, with fewer
complications. The real benefit of this technique in the short and long term is
unknown. This systematic review aims to compare laparoscopic gastric plication
and laparoscopic sleeve gastrectomy for obesity treatment. METHODS: Clinical
trials were identified in MEDLINE, Embase, Cochrane, LILACS, BVS, SCOPUS, and
CINAHL databases. Comparison of LGP and laparoscopic sleeve gastrectomy (SG)
included hospital stay, operative time, loss of hunger feeling, body mass index
loss (BMIL), percentage of excess weight loss (%EWL), complications, symptoms in
the postoperative period, and comorbidity remission or improvement. RESULTS: This
systematic review search included 17,423 records. Eight studies were selected for
meta-analysis. There is no difference in operative time, hospital stay, and
complications. Patients in the SG group had improved loss of hunger feeling. BMIL
was better in the SG group at 12 and 24 months [mean difference (MD) - 2.19, 95%
confidence interval (CI) - 3.10 to - 1.28, and MD - 4.59, 95% CI - 5.55 to -
3.63, respectively]. SG showed improved %EWL compared with gastric plication in
3, 6, 12, and 24 months. However, no difference was found in %EWL long-term
results (24 and 36 months). Patients who underwent LGP had more sialorrhea. SG
showed better results in diabetes remission. CONCLUSIONS: SG showed improved
weight loss when compared with LGP, with better satiety, fewer symptoms in the
postoperative period, and improved diabetes remission.
PMID- 29951785
TI - Correction to: The Impact of Obesity and Metabolic Surgery on Chronic
Inflammation.
AB - In Table 4 the column labeled "p values" and its data should be deleted.
PMID- 29951786
TI - Photocontact Dermatitis and Its Clinical Mimics: an Overview for the Allergist.
AB - Photo-contact dermatitis (PCD) describes the adverse cutaneous reaction that
occurs in some patients as a result of simultaneous exposure to a contactant and
to light. PCD can be subdivided into photo-allergic and photo-irritant dermatitis
depending on whether the contactant respectively invokes an allergic or irritant
reaction. Photo-irritant reactions are commonly caused by plants, psoralens, and
medications taken internally, whereas photo-allergic reactions are commonly
caused by sunscreens and topical nonsteroidal anti-inflammatory medications. The
work-up of photo-contact dermatitis includes a thorough history and physical exam
augmented by patch and/or photopatch testing, as the cornerstone of treatment for
PCD is identification and avoidance of the irritating or allergenic chemical.
Photo-contact dermatitis has the potential to significantly impact quality of
life, so an informed approach to diagnosis and management is critical. Clinical
mimics of PCD include polymorphic light eruption, solar urticaria, actinic
prurigo, hydroa vacciniforme, cutaneous porphyrias, and systemic disorders with
photosensitivity such as lupus and dermatomyositis. Herein, we review the
clinical presentation, differential diagnosis (including the clinical mimics
mentioned above), pathogenic mechanisms, diagnostic testing, and therapeutic
considerations for PCD.
PMID- 29951787
TI - Multilocus sequence typing for phylogenetic view and vip gene diversity of
Bacillus thuringiensis strains of the Assam soil of North East India.
AB - An agriculturally important insecticidal bacterium, Bacillus thuringiensis have
been isolated from the soil samples of various part of Assam including the
Kaziranga National Park. Previously, the isolates were characterized based on
morphology, 16S rDNA sequencing, and the presence of the various classes' crystal
protein gene(s). In the present study, the phylogenetic analysis of a few
selected isolates was performed by an unambiguous and quick method called the
multiple locus sequence typing (MLST). A known B. thuringiensis strain kurstaki
4D4 have been used as a reference strain for MLST. A total of four the MLST locus
of housekeeping genes, recF, sucC, gdpD and yhfL were selected. A total of 14
unique sequence types (STs) was identified. A total number of alleles identified
for the locus gdpD and sucC was 12, followed by locus yhfL was 11, however, only
6 alleles were detected for the locus recF. The phylogenetic analysis using MEGA
7.0.26 showed three major lineages. Approximately, 87% of the isolates belonged
to the STs corresponding to B. thuringiensis, whereas two isolates, BA07 and
BA39, were clustered to B. cereus. The isolates were also screened for the
diversity of vegetative insecticidal protein (vip) genes. In all, 8 isolates
showed the presence of vip1, followed by 7 isolates having vip2 and 6 isolates
for vip3 genes. The expression of Vip3A proteins was analyzed by western blot
analyses and expression of the Vip3A protein was observed in the isolate BA20.
Thus, the phylogenetic relationship and diversity of Bt isolates from Assam soil
was established based on MLST, in addition, found isolates having vip genes,
which could be used for crop improvement.
PMID- 29951789
TI - Inhibition of autophagy significantly increases the antitumor effect of
Abiraterone in prostate cancer.
AB - PURPOSE: Abiraterone acetate (AA) plus prednisone is an approved treatment of
advanced prostate cancer (PCa). Autophagy is linked to drug resistance in
numerous types of cancers. We hypothesized, that upregulation of autophagy is one
of the mechanisms by which PCa cells survive AA anti-tumor treatment and
therefore evaluated the potential effect of a combination with autophagy
inhibition. METHODS: Human PCa LNCaP cell lines were cultured in steroid-free
medium and treated with AA. Autophagy was inhibited by 3-methyladenine,
chloroquine and ATG5 siRNA knock-down. Cell viability and apoptosis was assessed
by flow cytometry and fluorescence microscopy, and autophagy was monitored by
immunohistochemistry, AUTOdot and Western blotting. RESULTS: Western blot
revealed upregulation of ATG5 and LC3 II with a reduction of p62 protein
expression in AA-treated cells, indicating upregulation of autophagy. These data
were supported by results obtained with immunocytochemistry and AUTOdot assays.
Using flow cytometry, we showed that combining AA with autophagy inhibition
significantly impaired cell viability (1.3-1.6-fold, p < 0.001) and increased
apoptosis (1.4-1.5-fold, p < 0.001) compared to AA treatment alone. CONCLUSIONS:
AA activates autophagy as a cytoprotective mechanism in LNCaP prostate cancer
cells and targeting of autophagy enhances the antitumor effect of the compound.
PMID- 29951788
TI - Management of KRAS-Mutant Non-Small Cell Lung Cancer in the Era of Precision
Medicine.
AB - OPINION STATEMENT: The discovery of genomic alterations that drive the
development and progression of non-small cell lung cancer (NSCLC) has transformed
how we treat metastatic disease. However, the promise of precision medicine
remains elusive for the most commonly mutated oncogene in NSCLC, KRAS. This is
perhaps due to the substantial heterogeneity within the broader genomic context
of KRAS-mutant NSCLC. At this time, approaches for treating metastatic KRAS
mutant NSCLC mirror those for treating NSCLC that lacks a known driver mutation,
including standard chemotherapeutic and immunotherapeutic approaches. Ongoing
research aims to define further subgroups of KRAS-mutant NSCLC based on mutation
subtype and co-occurring mutations. These efforts offer the potential to optimize
standard-of-care regimens within these emerging subgroups and harness innovative
strategies to realize precision medicine in this setting.
PMID- 29951790
TI - Elderly patients aged >= 75 years with locally advanced prostate cancer may
benefit from local treatment: a population-based propensity score-adjusted
analysis.
AB - OBJECTIVE: To evaluate whether elderly patients aged >= 75 years with locally
advanced prostate cancer (LAPC) may benefit from local treatment (LT). METHODS:
Elderly patients aged >= 75 years with non-metastatic cT3-4 LAPC who were treated
with LT [radical prostatectomy (RP), radiation therapy (RT)] or non-LT (NLT) were
identified. After propensity score matching (PSM), cancer-specific mortality
(CSM) and other-cause mortality (OCM) rates were assessed. In the assessment of
LT vs. NLT and RP vs. RT, multivariable competing risk regression (MVA CRR)
analysis was used. RESULTS: 368 and 482 paired patients were matched for LT vs.
NLT and RP vs. RT, respectively. 5 and 10 years CSM rates were 9.4 vs. 18.5% in
LT and 24.9 vs. 29.3% in NLT-treated patients, respectively (P < 0.0001). 5 and
10 years CSM rates were 3.4% vs. 8.6% in RP and 6.7% vs. 15.1% in RT-treated
patients, respectively (P = 0.10). In the MVA CRR model, after PSM, NLT resulted
in higher CSM rates in Gleason score 8-10 [subhazard ratio (sHR) = 2.83, P <
0.001], cT3b/4 (sHR = 3.97/2.56, P = 0.003/0.002), cN0 (sHR = 2.52, P < 0.001) or
PSA > 10 ng/ml [sHR (PSA = 10.1-20 ng/ml) = 4.59, P = 0.03; sHR (PSA > 20 ng/ml)
= 2.77, P = 0.001] patients compared with LT. However, no statistically
significant difference in CSM was observed between RP and RT, except for cT3a
patients in whom higher CSM rates were noted for RT compared with RP (sHR = 3.91,
P = 0.02). CONCLUSION: LAPC patients may benefit from local treatment despite
advanced age. However, this benefit was only seen in patients with cT3b/4,
Gleason score 8-10, cN0 or PSA > 10 ng/ml.
PMID- 29951791
TI - Neurogenic bowel management for the adult spinal cord injury patient.
AB - BACKGROUND: Bowel function can be markedly changed after a spinal cord injury
(SCI). These changes, and the care associated with managing the changes, can
greatly impact a person's quality of life over a lifetime. PURPOSE: The purpose
of the SIU-ICUD workgroup was to identify, assess, and summarize evidence and
expert opinion-based themes and recommendations regarding bowel function and
management in SCI populations. METHODS: As part of the SIU-ICUD joint
consultation of Urologic Management of the Spinal Cord Injury, a workgroup was
formed and comprehensive literature search of English language manuscripts
regarding bowel physiology and management plans for the SCI patient. Articles
were compiled, and recommendations in the chapter are based on group discussion
and follow the Oxford Centre for Evidence-based Medicine system for levels of
evidence (LOEs) and grades of recommendation (GORs). RESULTS: Neurogenic bowel
symptoms are highly prevalent in the SCI population. Patients with injuries above
the conus medullaris have increased bowel motility and poor anorectal sphincter
relaxation. Patients with injuries below the conus are more likely to have an
areflexic colon and low sphincter tone. Conservative management strategies
include diet modification and anorectal stimulation. There are few evidence-based
pharmacologic interventions, which improve fecal transit time. Intestinal ostomy
can be an effective treatment for reducing hours spent per week on bowel
management and colostomy may be easier to manage than ileostomy due to solid vs
liquid stool. CONCLUSIONS: By understanding physiology and treatment options,
patients and care teams can work together to achieve goals and maximize quality
of life after injury.
PMID- 29951792
TI - Correction to: The key role of CYC2 during meiosis in Tetrahymena Thermophila.
AB - In the original publication, the funding information was incorrectly published.
The correct funding information is provided in this correction. This work is
supported by grants from the Projects of International Cooperation and Exchanges
Ministry of Science and Technology of China (2013DFG32390) and the National
Natural Science Foundation of China (31472059) to X.S. X.S is a recipient of the
Young Thousand Talents program (KJ2070000026).
PMID- 29951793
TI - Ibrutinib for Treating Waldenstrom's Macroglobulinaemia: An Evidence Review Group
Perspective of a NICE Single Technology Appraisal.
AB - As part of its Single Technology Appraisal (STA) process, the UK National
Institute for Health and Care Excellence (NICE) invited the manufacturer of
ibrutinib (Janssen) to submit evidence on the clinical and cost effectiveness of
ibrutinib for treating Waldenstrom's macroglobulinaemia (WM). The School of
Health and Related Research Technology Assessment Group at the University of
Sheffield was commissioned to act as the independent Evidence Review Group (ERG).
The ERG produced a critical review of the evidence for the clinical and cost
effectiveness of ibrutinib based on the company's submission to NICE. The
clinical evidence was derived from one phase II, single-arm, open-label study of
ibrutinib in adult patients with WM who had received at least one prior therapy
(Study 1118E) and an indirect comparison using a matched cohort from a
retrospective European chart review of patients receiving various treatments for
WM. The indirect comparison suggested a hazard ratio for progression-free
survival (PFS) of 0.25 (95% confidence interval 0.11-0.57). The ERG had concerns
regarding the high risk of bias in Study 1118E, the limited generalisability of
the study, and the absence of randomised controlled trial evidence. The company's
Markov model assessed the cost effectiveness of ibrutinib versus
rituximab/chemotherapy for patients with relapsed/refractory (R/R) WM from the
perspective of the National Health Service (NHS) and Personal Social Services
(PSS) over a lifetime horizon. Based on the company's original Patient Access
Scheme (PAS), the company's probabilistic model generated an incremental cost
effectiveness ratio (ICER) for ibrutinib versus rituximab/chemotherapy of L58,905
per quality-adjusted life-year (QALY) gained. Following a critique of the model,
the ERG's preferred analysis, which corrected cost errors and used the observed
mortality rate from Study 1118E, generated a probabilistic ICER of L61,219 per
QALY gained. Based on this amended model, additional exploratory analyses
produced ICERs for ibrutinib that were > L60,000 per QALY gained. Subsequently,
the company offered to provide ibrutinib at a price that resulted in ibrutinib
being cost effective within the Cancer Drugs Fund (CDF). The Committee
recommended ibrutinib for use in the CDF as an option for treating WM in adults
who have had at least one prior therapy, only if the conditions in the managed
access agreement for ibrutinib are followed.
PMID- 29951794
TI - Toxicity of seven insecticides to different developmental stages of the whitefly
Bemisia tabaci MED (Hemiptera: Aleyrodidae) in multiple field populations of
China.
AB - Chemical control is important in the management of the tobacco whitefly, Bemisia
tabaci (Gennadius) (Hemiptera: Aleyrodidae). Susceptibility of B. tabaci to
insecticides may vary among different developmental stages and geographical
populations. In this study, we examined toxicity of seven commonly-used
insecticides to B. tabaci MED in four field populations from China. Avermectin
has high level of toxicity to all stages of B. tabaci MED in all four
populations. Cyantraniliprole and sulfoxaflor have high toxicity to adults.
Spirotetramat, cyantraniliprole and flonicamid have high toxicity to nymphs but
not adults. Acetamiprid, cyantraniliprole and sulfoxaflor have high toxicity to
eggs. However, the relative toxicity of B. tabaci MED to these chemicals varied
across different populations, with little consistency in population differences
across developmental stages. Our findings together with some instances where LC95
values were higher than field recommended dosages indicate field-evolved
resistance to insecticides (such as thiamethoxam and sulfoxaflor) and stage
specific mechanisms that will influence effective control of B. tabaci MED by
insecticides.
PMID- 29951795
TI - Diversity and abundance of arsenic methylating microorganisms in high arsenic
groundwater from Hetao Plain of Inner Mongolia, China.
AB - Arsenic methylation is regarded as an effective way of arsenic detoxification.
Current knowledge about arsenic biomethylation in high arsenic groundwater
remains limited. In the present study, 16 high arsenic groundwater samples from
deep wells of the Hetao Plain were investigated using clone library and
quantitative polymerase chain reaction (qPCR) analyses of arsM genes as well as
geochemical analysis. The concentrations of methylated arsenic (including
monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) varied from 2.40 to
16.85 MUg/L. Both bacterial and archaeal arsenic methylating populations were
detected in the high arsenic aquifer. They were dominated by Proteobacteria,
Firmicutes, Gemmatimonadetes, Nitrospirae, Methanomicrobia and a large
unidentified group. The abundances of predominant populations were correlated
positively to either total organic carbon or total arsenic and arsenite
concentrations. The arsM gene abundances in high arsenic groundwater ranged from
below detection to 5.71 * 106 copies/L and accounted for 0-3.320/00 of total
bacterial and archaeal 16S rRNA genes. The arsM gene copies in high arsenic
groundwater showed closely positive correlations with methylated arsenic
concentrations. The overall results implied that arsenic methylating
microorganisms were abundant and diverse in high arsenic groundwater. This was
the first study of arsenic methylating microbial communities in high arsenic
groundwater aquifers and might provide useful information for arsenic
bioremediation in groundwater systems.
PMID- 29951796
TI - Is Barrett's-Associated Esophageal Adenocarcinoma a Clonal Disease?
AB - In this study, we argue that the basic clonal unit that makes up the Barrett's
segment is at the level of the gland. There is expansion of this clonal unit, the
gland, by fission, and there is evidence that the Barrett's segment is itself a
clonal proliferation. Barrett's esophagus arises from both goblet cell-containing
metaplasia and non-goblet cell-containing metaplasia and may arise from a stable
clone, but the genomic changes occurring are subject to selection, usually with
little or no evolution, appearing indolent from the evolutionary perspective.
Genomic changes leading to dysplastic phenotypes are selected, but without any
single clone predominating within the segment.
PMID- 29951798
TI - Unusual proximal fragment migration of an os peroneum fracture with associated
peroneus longus tendon injury-a tree often hides a forest.
AB - We report the case of a 55-year-old male patient who presented to the emergency
department after sustaining a right ankle trauma. Swelling and tenderness of the
lateral aspect of the right ankle were present on physical examination without
evidence of motor or sensory deficit. Ankle radiographs were performed and showed
two bony fragments, the first located postero-inferiorly to the cuboid bone while
the second was adjacent to the tip of the lateral malleolus. The diagnosis of an
os peroneum fracture was made with high suspicion of an associated peroneus
longus tendon rupture. Computed tomography (CT) and magnetic resonance imaging
(MRI) of the right ankle confirmed the diagnosis of a subtotal retracted
tendinous rupture. Successful surgical repair of the injured tendon was
performed. This article illustrates the imaging findings of an os peroneum
fracture with its associated tendinous injury and reviews the literature.
PMID- 29951797
TI - Long-Term Outcomes of Immunosuppression-Naive Steroid Responders Following
Hospitalization for Ulcerative Colitis.
AB - BACKGROUND: Requirement for hospitalization in ulcerative colitis (UC) is a
marker of severity of disease. However, the paradigm of when to escalate therapy
in such patients and the benefits of early immunomodulator initiation is less
well established. AIM: To examine the benefits of early therapy escalation in
immunosuppression-naive patients hospitalized with severe ulcerative colitis
responsive to steroids. METHODS: We identified hospitalized UC patients who were
immunosuppression naive at index hospitalization and responded to intravenous
steroids, not requiring medical or surgical rescue therapy. The 'therapy
escalated' group comprised of those who were initiated on immunomodulators within
3 months of hospitalization. The need for colectomy at 12 months was compared to
the 'not escalated' group who remained on non-immunosuppressive therapy. RESULTS:
Among 133 immunosuppressive naive patients hospitalized for ulcerative colitis,
13 (9.8%) who responded to intravenous steroids and did not require rescue
therapy underwent colectomy by 1 year. Among 123 patients who escalated to either
immunomodulators (n = 46, 37%) or remained on non-immunosuppressive therapy (92%
on 5-ASA), there was no difference in the need for colectomy at 1 year (10.8 vs.
7.8%; multivariate OR 1.29, 95% CI 0.35-4.74). There was also no difference in
the time to colectomy between the two groups (p = 0.55). CONCLUSION:
Immunosuppression-naive ASUC patients who respond to intravenous steroids remain
at risk for colectomy. Immunomodulator initiation by 3 months did not reduce risk
of colectomy at 1 year. There is an important need for prospective studies
identifying thresholds for therapy escalation in UC.
PMID- 29951799
TI - Atrioventricular valve disease: challenges and achievements in percutaneous
treatment.
AB - Percutaneous treatment of atrioventricular (AV) valve disease has long been
restricted to therapy of mitral stenosis, and was only lately expanded to mitral
regurgitation. 15 years ago the MitraClip edge to edge repair was first applied
to human pathology. In Europe, German centers were the first to widely adopt this
technique in patients with mitral regurgitation and high or inappropriate risk
for surgery. Given the exponential rise in implantation procedures, expertise of
the operators and investigator initiated investigations substantially contributed
to improvements in procedural processes and patient selection. Meanwhile,
additional techniques to repair the mitral and tricuspid valve were introduced to
German interventionalists, both reconstructive techniques as well as first
experiences with transcatheter implantation of mitral valve bioprostheses. Of
note, specialized Heart Valve referral Centers catalyzed the adoption of these
techniques. This review summarizes the contributions of German Heart Centers to
recent developments in percutaneous therapy of AV valve disease.
PMID- 29951802
TI - Body mass index and all-cause mortality in heart failure patients with normal and
reduced ventricular ejection fraction: a dose-response meta-analysis.
AB - BACKGROUND: For patients with heart failure, there is an inverse relation between
body mass index (BMI) and mortality, sometimes called the obesity-paradox.
However, the relationship might be either U- or J-shaped and might differ between
patients with reduced (HFrEF) or preserved left ventricular ejection fraction
(HFpEF). We sought to investigate this further in a dose-response meta-analysis
of published studies. METHODS: PubMed and Embase from June 1980 to April 2017
were searched for prospective cohort studies evaluating associations between BMI
and all-cause mortality in patients with HFrEF (LVEF < 40%) or HFpEF (LVEF >=
50%). Summary estimated effect sizes were obtained by using a random-effects
model. Potential non-linear relationships were evaluated by using random-effects
restricted cubic spline models. RESULTS: Ten studies were identified that
included 96,424 patients of whom 59,263 had HFpEF (mean age 68 years of whom 38%
were women) and 37,161 had HFrEF (mean age 60 years of whom 17% were women). For
patients with HFpEF, the summary hazard ratio (HR) for all-cause mortality was:
0.93 (95% CI 0.89-0.97) per 5 units increase in BMI (I2 = 75.8%, p for
heterogeneity = 0.01 and Begg's test, p = 1.0, Egger's test, p = 0.29) but the
association was U-shaped (p for non-linearity < 0.01) with the nadir of risk at a
BMI of 32-33 kg/m2. For patients with HFrEF, the summary HR for all-cause
mortality was: 0.96 (95% CI 0.92-0.99) (I2 = 95%, p for heterogeneity < 0.001 and
Begg's test, p = 0.45, Egger's test, p = 0.01). The relationship was also U
shaped (p < 0.01), although 'flatter' than for HFpEF, with the nadir at a BMI of
33 kg/m2. CONCLUSIONS: For patients with heart failure, the relation between BMI
and mortality is U-shaped with a similar nadir of risk for HFpEF and HFrEF at a
BMI of 32-33 kg/m2. Whether interventions that alter weight in either direction
can alter risk is unknown.
PMID- 29951801
TI - Transcatheter aortic valve implantation in Germany.
AB - Over the past years, there has been a tremendous evolution of transcatheter
aortic valve implantation (TAVI) that turned a novel revolutionary approach to a
mature concept. Peri-procedural complications and mortality rates have markedly
decreased; hence, TAVI became an integral component of the treatment strategy for
patients with severe aortic stenosis and now is the preferred therapy in elderly
patients with moderate to high or prohibitive operative risk. This successful
development would not have been possible without the joint efforts of clinicians,
scientists, engineers, and many others from around the world. In this context,
Germany has been one of the forerunners in implanting transcatheter heart valves,
as evidenced not only by the high numbers of procedures, but in particular by
some individual pioneering achievements. Here, we picture German contributions in
the field of TAVI that had impact on clinical practice, including first-in-man
experience, CE mark trials, randomized studies, large registries, and other
procedurally relevant aspects.
PMID- 29951800
TI - Hypertension: history and development of established and novel treatments.
AB - BACKGROUND: This article summarizes the emerging field of hypertension over the
last decades. It covers paradigm shifts on hypertension from an undefined
cardiovascular condition to the most relevant cardiovascular modifiable risk
factor and the developments of drug treatments and interventional treatments to
improve cardiovascular outcomes. METHODS: We performed a selective literature
research in PubMed on trials published in the past until 2018 without time
restrictions and covered unpublished trials disclosed in ClinicalTrials.org.
RESULTS: The development of treatments of hypertension is a success story
covering many decades from the early attempts with drug treatments, development
of tolerable and effective medications to interventional techniques involving
renal denervation, AV fistulas, and autonomic devices. Novel guidelines define
new definitions and treatment targets of hypertension, which are a matter of
ongoing discussion. CONCLUSION: Despite the development of tolerable and
effective drugs, new treatments in the field of neuroendocrine modulation by
drugs and devices are still under development trying to further improve treatment
of patients with hypertension and to further reduce cardiovascular events in
those individuals.
PMID- 29951803
TI - Polymer-free drug-coated coronary stents in diabetic patients at high bleeding
risk: a pre-specified sub-study of the LEADERS FREE trial.
AB - OBJECTIVE: Diabetics are at increased risk after stent implantation and
potentially sensitive to the type of stent and dual anti-platelet therapy (DAPT).
The randomized, double-blind LEADERS FREE trial compared 2432 patients at high
bleeding risk (HBR) receiving either a polymer-free BA9-coated stent (DCS) or a
bare metal stent (BMS) with 1 month of DAPT, and showed superior safety and
efficacy of the DCS at 2 years. We report outcomes at 2 years of the pre
specified diabetic subgroup. METHODS AND RESULTS: The diabetic sub-group
comprised 805 (33.1%) patients; 262 (10.8%) were insulin-dependent (IDDM).
Compared to non-diabetics, diabetics were younger and had more risk factors and
multi-vessel disease. They suffered higher rates of death (15.6 vs. 12.2%, p =
0.01), cardiac death (8.3 vs. 5.9%, p = 0.02), myocardial infarction (MI) (11.1
vs. 7.8%, p = 0.009) and definite/probable stent thrombosis (3.1 vs. 1.7%, p =
0.01), but rates of clinically-indicated TLR (9.1 vs. 9.5%, p = 0.93) and BARC 3
5 bleeding (10.2 vs. 8.4%, p = 0.20) were comparable. Compared to diabetic
patients treated with a BMS, diabetic DCS recipients required less clinically
driven TLR (6.3 vs. 12.2%, p = 0.006). The primary safety endpoint (cardiac
death, MI, definite/probable stent thrombosis) occurred numerically less
frequently in the DCS group (14.9 vs. 19.7%, p = 0.10), and was significantly
lower in IDDM patients (13.8 vs. 25.4%, p = 0.03). BARC 3-5 was similar for
patients treated with DCS (9.9%) and BMS (10.5%, p = 0.84). CONCLUSIONS: In
diabetic HBR patients, DCS significantly reduced re-intervention rates over BMS,
and showed a strong trend towards a safety benefit at 2 years. CLINICAL TRIAL
REGISTRATION: ClinicalTrials.gov number: NCT01623180.
PMID- 29951804
TI - Novel ECG-based scoring tool for prediction of takotsubo syndrome.
AB - BACKGROUND: Takotsubo syndrome (TS) usually involves ECG changes mimicking acute
myocardial infarction (AMI). The differentiation of both disorders is crucial for
selection of appropriate treatment. The aim of this study was to assess ECG
parameters in patients with TS and AMI, and try to establish a scoring tool for
TS prediction. METHODS: The study consisted of two study parts: evaluation and
validation cohorts. Overall, the study included 82 patients with TS and 141
subjects with AMI. In addition to the major demographic characteristics and
comorbidities, the following ECG parameters were analyzed: heart rate, QRS
duration, QTc, QRS amplitudes in frontal and precordial leads, frequencies for ST
segment elevation, combined sign of positive ST-segment elevation in -aVR and
absent in V1, negative T-wave in lead I and positive in III, inverted or biphasic
T-waves in V2-V5, T-wave inversions in frontal and precordial leads. All
significant variables were identified in univariate regression analysis and
further included for multivariate logistic regression analysis predicting TS.
RESULTS: TS was frequently diagnosed in women and in elderly patients. Presence
of ST-segment elevation, inverted/biphasic T-waves in V2-V5, QRS amplitudes in
frontal and precordial leads were significantly different in evaluation group. By
multivariate regression analysis sex, QRS amplitudes in frontal, inverted or
biphasic T-waves in septal leads and QTc were identified as powerful variables to
calculate TS probability. The diagnostic accuracy of the developed 6-points-TS
score was then evaluated in the validation group. Thus, no subject with a TS
score of >= 5 had AMI (specificity 99%, sensitivity > 92%). CONCLUSION: The
developed ECG-based TS-score model may be a useful complimentary tool for TS
prediction in acute clinical setting.
PMID- 29951806
TI - Erratum to: Gene Regulation, Two Component Regulatory Systems, and Adaptive
Responses in Treponema Denticola.
PMID- 29951805
TI - Current developments in cardiac rhythm management devices.
AB - Endocardial pacing has experienced a tremendous evolution since the 1960s. A lot
of challenges associated with pacemaker and ICD devices have already been
successfully targeted. However, a relevant number of problems have not been
solved to date. Not all patients with accepted indication for biventricular
pacing have benefited from cardiac resynchronisation therapy (CRT) despite
extensive efforts to reduce the rate of non-responders. Current strategies to
optimize lead position, multipolar left-ventricular (LV) pacing leads, new
strategies to gain access to the left-ventricle (atrial transseptal or
ventricular transseptal access) or alternative right-ventricular (septal, His
bundle pacing) pacing sites, and "leadless" LV pacing have the potential to
increase response to device-based heart-failure treatment. The opportunity of
pacemaker and ICD remote monitoring led to relevant improvements in therapy
management by timely detection of events requiring medical or invasive
interventions (e.g., external cardioversion of atrial fibrillation, increasing
effective biventricular pacing, catheter ablation of ventricular tachycardias, or
changes in heart-failure medication). Two completely endocardial leadless "all-in
one" pacemaker systems recently became available. Besides these innovations, new
"synergistic" therapy concepts combining catheter ablation and device therapy
proved to affect clinical endpoints (e.g., ATAAC study and CASTLE-AF study).
PMID- 29951807
TI - Clinical application of postoperative non-invasive positive pressure ventilation
after lung cancer surgery.
AB - OBJECTIVE: The purpose of this study was to clarify the clinical efficacy of
postoperative non-invasive positive pressure ventilation (PONIV) after pulmonary
lobectomy in patients with lung cancer. METHODS: From August 2010 and July 2015,
143 patients with lung cancer who underwent pulmonary lobectomy were
retrospectively reviewed. PONIV was used immediately after surgery until the
morning of postoperative day (POD) 1. Arterial blood gas was analyzed before and
just after surgery (POD0) and on POD1. Oxygenation ability was perioperatively
assessed by PaO2/FiO2 ratio, alveolar-arterial oxygen difference (A-aDO2), and
respiratory index (A-aDO2/PaO2). RESULTS: 112 patients received PONIV. From POD0
to POD1, the PaO2/FiO2 ratio significantly improved in all patients who received
PONIV (333 +/- 83 to 359 +/- 47 mmHg, p = 0.004). Moreover, A-aDO2 and
respiratory index significantly decreased following PONIV. PONIV significantly
improved the PaO2/FiO2 ratio in patients with PaO2/FiO2 ratio of <= 300 on POD0,
older age (>= 70 years), higher body mass index (>= 25 kg/m2), and longer one
lung ventilation time (>= 180 min). There was no respiratory failure requiring
mechanical ventilation and no mortality. CONCLUSIONS: PONIV effectively improved
oxygenation in patients undergoing pulmonary lobectomy in patients with poor
status, especially in patients with PaO2/FiO2 ratio of <= 300 on POD0. PONIV
could be an option of perioperative management for major thoracic surgery.
PMID- 29951808
TI - Correction to: Development of a simple device enabling percutaneous flow
regulation for a small vascular graft for a Blalock-Taussig shunt capable of flow
regulation: complete translation of an original article originally published in
Pediatric Cardiology and Cardiac Surgery (154-159, 2016: vol. 32).
AB - In the original publication of the article, the title was incorrectly published.
PMID- 29951809
TI - Letter to the Editor Regarding "Preoperative Digital Subtraction Angiography in
Incidental Unruptured Intracranial Aneurysms".
PMID- 29951810
TI - Extreme hypomagnesemia: characteristics of 119 consecutive inpatients.
AB - Extreme hypomagnesemia (hypoMg) can be encountered in many situations, but little
data currently exist. Our aim is to describe the epidemiological, clinical,
etiological characteristics, and the biological abnormalities of consecutive
inpatients with extreme hypomagnesemia. In our observational monocentric study,
between 1st July 2000 and April 2015, all inpatients with extreme hypomagnesemia,
defined by at least one plasma magnesium concentration (PMg) below 0.3 mmol/L,
were included. Demographic, clinical, biological characteristics and the drugs
prescribed before the qualifying PMg measurement were retrospectively collected.
41,069 patients had at least one PMg assessment. The prevalence of extreme
hypomagnesemia is 0.3% (119 inpatients). The median age is 70 years, 52% are
women. The patients were mainly hospitalized in intensive care (n = 37, 31.1%),
oncology (n = 21, 17.6%), gastroenterology (n = 18, 15.1%) and internal medicine
(n = 16, 13.4%) departments. One hundred patients (84%) had a medical history of
gastrointestinal disease (39% with bowel resections, 24% with stoma), and 50
(42%) had a cancer history. The drugs most commonly prescribed (known to induce
hypoMg) are proton pump inhibitors (PPI) (n = 77, 70%), immunosuppressive
regimens (n = 25, 22.5%), platinum salt-based chemotherapies (n = 19, 17.1%), and
diuretics (n = 22, 19.8%). The suspected causes of hypomagnesemia are often
multiple, but drugs (46%, including PPI in 19%) and chronic gastrointestinal
disorders (37%) are prominent. Associated electrolyte disturbances include
hypocalcemia (77%) and mild hypokalemia (51%). The 1-month mortality from all
causes is 16%. Extreme hypomagnesemia is rare in inpatients, and is frequently
associated with severe hypocalcemia. Digestive disorders and drugs are the main
contributory causes.
PMID- 29951812
TI - Adult Intestine Aging Model.
AB - The Drosophila adult has an intestine composed of a series of differentiated
cells and tissue stem cells, all of which are similar to the mammalian intestinal
cells. The aged adult intestine shows apparent characteristics such as
multilayering of absorptive cells, misexpression of cell type-specific genes, and
hyperproliferation of stem cells. Recent studies have revealed various gene
networks responsible for progression of these aged phenotypes. The molecular
mechanism for senescence of the Drosophila adult midgut and its relation with the
corresponding mechanism in mammals are overviewed. In addition, a basic method
for observing aged phenotypes of the midgut is described.
PMID- 29951811
TI - Drosophila as a Model Organism.
AB - Drosophila melanogaster has been widely used in classical and modern genetics for
more than 100 years. The history of the Drosophila model in the study of various
aspects of life sciences will be summarized in this chapter. Furthermore,
commonly used techniques and tools with Drosophila models will be briefly
described, with a special emphasis on the advantages of Drosophila models in the
study of various human diseases.
PMID- 29951813
TI - Alzheimer's Disease Model System Using Drosophila.
AB - Alzheimer's disease (AD) is the most epidemic neuronal dysfunctions among elderly
people. It is accompanied by neuronal disorders along with learning and memory
defects, as well as massive neurodegeneration phenotype. The presence of
intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques,
called senile plaques (SPs), and brain atrophy are typically observed in the
brains of AD patients. It has been over 20 years since the discovery that small
peptide, called beta-amyloid (Abeta), has pivotal role for the disease formation.
Since then, a variety of drugs have been developed to cure AD; however, there is
currently no effective drug for the disorder. This therapeutic void reflects
lacks of ideal model system, which can evaluate the progression of AD in a short
period. Recently, large numbers of AD model system have been established using
Drosophila melanogaster by overproducing Abeta molecules in the brain. These
systems successfully reflect some of the symptoms along with AD. In this review,
we would like to point out "pros and cons" of Drosophila AD models.
PMID- 29951814
TI - Parkinson's Disease Model.
AB - Parkinson's disease (PD) is the second most common neurodegenerative disease
worldwide. It is known that there are many factors, either genetic or
environmental factors, involved in PD, but the mechanism of PD is still not fully
understood. Several animal models have been established to study the mechanisms
of PD. Among these models, Drosophila melanogaster has been utilized as a
valuable model to get insight into important features of PD. Drosophila
melanogaster possesses a well-developed dopaminergic (DA) neuron system which is
known to play an important role in PD pathogenesis. The well understanding of DA
neurons from early larval through adult stage makes Drosophila as a powerful
model for investigating the progressive neurodegeneration in PD. Besides, the
short life cycle of Drosophila melanogaster serves an advantage in studying
epidemiological features of PD. Most of PD symptoms can be mimicked in Drosophila
model such as progressive impairment in locomotion, DA neuron degeneration, and
some other non-motor symptoms. The Drosophila models of PD, therefore, show a
great potential in application for PD genetic and drug screening.
PMID- 29951815
TI - Repeat Expansion Disease Models.
AB - Repeat expansion disorders are a group of inherited neuromuscular diseases, which
are caused by expansion mutations of repeat sequences in the disease-causing
genes. Repeat expansion disorders include a class of diseases caused by repeat
expansions in the coding region of the genes, producing mutant proteins with
amino acid repeats, mostly the polyglutamine (polyQ) diseases, and another class
of diseases caused by repeat expansions in the noncoding regions, producing
aberrant RNA with expanded repeats, which are called noncoding repeat expansion
diseases. A variety of Drosophila disease models have been established for both
types of diseases, and they have made significant contributions toward
elucidating the molecular mechanisms of and developing therapies for these
neuromuscular diseases.
PMID- 29951816
TI - Amyotrophic Lateral Sclerosis Model.
AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that
affects upper and lower motor neurons in the brain and the spinal cord. Due to
the progressive neurodegeneration, ALS leads to paralysis and death caused by
respiratory failure 2-5 years after the onset of symptoms. There is no effective
cure available. Most ALS cases are sporadic, without family history, whereas 10%
of the cases are familial. Identification of variants in more than 30 different
loci has provided insight into the pathogenic molecular mechanisms mediating
disease pathogenesis. Studies of a Drosophila melanogaster model for each of the
ALS genes can contribute to uncovering pathophysiological mechanism of ALS and
finding targets of the disease-modifying therapy. In this review, we focus on
three ALS-causing genes: TAR DNA-binding protein (TDP-43), fused in
sarcoma/translocated in liposarcoma (FUS/TLS), and chromosome 9 open reading
frame 72 (C9orf72).
PMID- 29951817
TI - Drosophila Charcot-Marie-Tooth Disease Models.
AB - Charcot-Marie-Tooth disease (CMT) was initially described in 1886. It is
characterized by defects in the peripheral nervous system, including sensory and
motor neurons. Although more than 80 CMT-causing genes have been identified to
date, an effective therapy has not yet been developed for this disease. Since
Drosophila does not have axons surrounded by myelin sheaths or Schwann cells, the
establishment of a demyelinating CMT model is not appropriate. In this chapter,
after overviewing CMT, examples of Drosophila CMT models with axonal neuropathy
and other animal CMT models are described.
PMID- 29951818
TI - Drosophila as a Model to Gain Insight into the Role of lncRNAs in Neurological
Disorders.
AB - It is now clear that the majority of transcription in humans results in the
production of long non-protein-coding RNAs (lncRNAs) with a variable length
spanning from 200 bp up to several kilobases. To date, we have a limited
understanding of the lncRNA function, but a huge number of evidences have
suggested that lncRNAs represent an outstanding asset for cells. In particular,
temporal and spatial expression of lncRNAs appears to be important for proper
neurological functioning. Stunningly, abnormal lncRNA function has been found as
being critical for the onset of neurological disorders. This chapter focus on the
lncRNAs with a role in diseases affecting the central nervous system with
particular regard for the lncRNAs causing those neurodegenerative diseases that
exhibit dementia and/or motor dysfunctions. A specific section will be dedicated
to the human neuronal lncRNAs that have been modelled in Drosophila. Finally,
even if only few examples have been reported so far, an overview of the
Drosophila lncRNAs with neurological functions will be also included in this
chapter.
PMID- 29951819
TI - Muscular Dystrophy Model.
AB - Muscular dystrophy (MD) is a group of muscle weakness disease involving in
inherited genetic conditions. MD is caused by mutations or alteration in the
genes responsible for the structure and functioning of muscles. There are many
different types of MD which have a wide range from mild symptoms to severe
disability. Some types involve the muscles used for breathing which eventually
affect life expectancy. This chapter provides an overview of the MD types, its
gene mutations, and the Drosophila MD models. Specifically, the Duchenne muscular
dystrophy (DMD), the most common form of MD, will be thoroughly discussed
including Dystrophin genes, their isoforms, possible mechanisms, and signaling
pathways of pathogenesis.
PMID- 29951820
TI - Drosophila As a Cancer Model.
AB - Over the last few decades, Drosophila cancer models have made great contributions
to our understanding toward fundamental cancer processes. Particularly, the
development of genetic mosaic technique in Drosophila has enabled us to
recapitulate basic aspects of human cancers, including clonal evolution, tumor
microenvironment, cancer cachexia, and anticancer drug resistance. The mosaic
technique has also led to the discovery of important tumor-suppressor pathways
such as the Hippo pathway and the elucidation of the mechanisms underlying tumor
growth and metastasis via regulation of cell polarity, cell-cell cooperation, and
cell competition. Recent approaches toward identification of novel therapeutics
using fly cancer models have further proved Drosophila as a robust system with
great potentials for cancer research as well as anti-cancer therapy.
PMID- 29951821
TI - From Drosophila Blood Cells to Human Leukemia.
AB - The hematopoietic system plays a critical role in establishing the proper
response against invading pathogens or in removing cancerous cells. Furthermore,
deregulations of the hematopoietic differentiation program are at the origin of
numerous diseases including leukemia. Importantly, many aspects of blood cell
development have been conserved from human to Drosophila. Hence, Drosophila has
emerged as a potent genetic model to study blood cell development and leukemia in
vivo. In this chapter, we give a brief overview of the Drosophila hematopoietic
system, and we provide a protocol for the dissection and the immunostaining of
the larval lymph gland, the most studied hematopoietic organ in Drosophila. We
then focus on the various paradigms that have been used in fly to investigate how
conserved genes implicated in leukemogenesis control blood cell development.
Specific examples of Drosophila models for leukemia are presented, with
particular attention to the most translational ones. Finally, we discuss some
limitations and potential improvements of Drosophila models for studying blood
cell cancer.
PMID- 29951822
TI - Diseases Associated with Mutation of Replication and Repair Proteins.
AB - Alterations in proteins that function in DNA replication and repair have been
implicated in the development of human diseases including cancer, premature
ageing, skeletal disorders, mental retardation, microcephaly, and
neurodegeneration. Drosophila has orthologues of most human replication and
repair proteins and high conservation of the relevant cellular pathways, thus
providing a versatile system in which to study how these pathways are corrupted
leading to the diseased state. In this chapter I will briefly review the diseases
associated with defects in replication and repair proteins and discuss how past
and future studies on the Drosophila orthologues of such proteins can contribute
to the dissection of the mechanisms involved in disease development.
PMID- 29951823
TI - Drosophila Models to Investigate Insulin Action and Mechanisms Underlying Human
Diabetes Mellitus.
AB - Diabetes is a group of metabolic diseases in which the patient shows elevated
levels of blood sugar. In healthy condition, there is the regulatory system that
maintains constant glucose levels in blood. It is accomplished by two hormones,
insulin and glucagon acting antagonistically. Insulin is produced in beta cells
in pancreas and secreted to blood. It specifically binds to its receptors on
plasma membrane and activates the intracellular signaling pathways. At the end,
glucose in blood are taken into the cells. The diabetes is classified into two
types. In type 1 diabetes (T1D), patients' pancreas fails to produce sufficient
insulin. Hence, in type 2 diabetes (T2D), the target cells of insulin fail to
respond to the hormone. The metabolic syndrome (MS) is characterized as a
prediabetes showing lowered responsiveness to insulin. Drosophila has been
expected to be a usefulness model animal for the diabetes researches. The
regulatory system maintaining homeostasis of circulating sugar in hemolymph is
highly conserved between Drosophila and mammals. Here, we summarize findings to
date on insulin production and its acting mechanism essential for glucose
homeostasis both in mammals and Drosophila. Subsequently, we introduce several
Drosophila models for T1D, T2D, and MS. As a consequence of unique genetic
approaches, new genes involved in fly's diabetes have been identified. We compare
their cellular functions with those of mammalian counterparts. At least three
antidiabetic drugs showed similar effects on Drosophila. We discuss whether these
Drosophila models are available for further comparative studies to comprehend the
metabolic diseases.
PMID- 29951824
TI - Metabolomics: State-of-the-Art Technologies and Applications on Drosophila
melanogaster.
AB - Metabolomics is one of the latest "omics" technology concerned with the high
throughput identification and quantification of metabolites, the final products
of cellular processes. The revealed data provide an instantaneous snapshot of an
organism's metabolic pathways, which can be used to explain its phenotype or
physiology. On the other hand, Drosophila has shown its power in studying
metabolism and related diseases. At this stage, we have the state-of-the-art
knowledge in place: a potential candidate to study cellular metabolism
(Drosophila melanogaster) and a powerful methodology for metabolic network
decipherer (metabolomics). Yet missing is advanced metabolomics technologies like
isotope-assisted metabolomics optimized for Drosophila. In this chapter, we will
discuss on the current status and future perspectives in technologies and
applications of Drosophila metabolomics.
PMID- 29951825
TI - Humanized Flies and Resources for Cross-Species Study.
AB - The completion of whole-genome sequences has greatly broadened our understanding
of genes and genomes. The availability of model organism databases facilitates
the sharing of information. However, it is still challenging to predict the
pathogenicity of missense mutations, and it is more difficult to evaluate the
functional impact of noncoding variants. What is more, it is a primary question
to understand what variants interact to express phenotypes. Powerful genetic
tools and resources available in Drosophila now make it much easier to replace
endogenous genes with exogenous DNA. This allows us to directly investigate and
compare the functions of orthologs, variants, and fragments in a single genetic
background, the value of which should be widely appreciated. To take one example,
we are currently studying so-called ultra-conserved elements, which have been
conserved over hundreds of millions of years of vertebrate evolution. Many highly
conserved elements are in noncoding regions and are thought to play a pivotal
role in gene regulation. We generated transgenic fly lines carrying human ultra
conserved elements for enhancer reporter assay and indeed observed the reporter
expression in one or more tissues of embryos and larvae in all elements tested.
Currently, transgenic human-ORF lines expressing human genes under the control of
GAL4/UAS system are also been developed, which will greatly facilitate the cross
species in Drosophila. In this chapter, I introduce useful tools and resources
available in Drosophila to nonspecialists, encouraging their further use in many
applications.
PMID- 29951826
TI - Designs for Flies + of Mice and Men: Design Approaches to Drosophila
melanogaster.
AB - Designs for Flies is an award-winning design-led interdisciplinary project
between KYOTO Design Lab (D-Lab), the Department of Applied Biology at the Kyoto
Institute of Technology (KIT) and Charcot-Marie-Tooth (CMT), Japan. Within the
framework of speculative design yet using an inclusive methodology, Frank
Kolkman, a young Dutch designer, took Professor Masamitsu Yamaguchi's climbing
assay experiment with Drosophila in his genetic mapping for CMT as the point of
departure. Kolkman sought to address two questions raised during his initial
research: "Could alternative strategies be used to generate interest from
pharmaceutical companies for obscure, complicated or 'unmarketable' diseases in
drug research?" and "Could transgenic Drosophila be used for the wildcard testing
of drug compounds directly by patients at home in the search for a possible
cure?" The chapter will describe its genesis, design process and the challenges
and potential of interdisciplinary projects of this nature along with the impact
of the resulting concept, which incorporated service, system, product and
interaction design. It won the Services and Systems category of the Dutch Design
Awards (DDW) in 2016, and Kolkman was named DDW's Young Designer of the Year in
October 2017. It was followed by Of Flies, Mice and Men: drosophila and the
interconnected landscape of genes, a Drosophila-related science communication
project by Marcel Helmer, Kolkman's successor as D-Lab Design Associate for which
the design brief was based on issues raised by the first project. This is also
described to highlight the differing issues, design approaches and results of
this science/design collaboration.
PMID- 29951827
TI - Application of a computational model of natural deep eutectic solvents utilizing
the COSMO-RS approach for screening of solvents with high solubility of rutin.
AB - The screening of natural deep eutectic solvents (NADES) to identify those with
the ability to strongly solvate rutin was conducted using the COSMO-RS
methodology. A NADES model was constructed that took into account the possible
ionic and neutral forms of its constituents. The distributions of all forms were
computed based on the equilibrium constants of neutralization reactions between
amino and carboxylic acids. The proposed model was validated against the
experimental solubilities of 15 NADES. A linear relationship between these data
and the estimated activity coefficient values was found. The screening
encompassed 126 different NADES. It was found that ten of them outperformed the
best reference system. The most effective two-component solvent comprised proline
combined with 2,3-diaminosuccinic acid, and the solubility of rutin in this
solvent was found to be 130% greater than its solubility in the best reference
system. The amino acids associated with the highest rutin solubilities were all
cyclic, and the use of carboxylic acids with two carboxyl groups and a main chain
consisting of two methylene groups with two amino substituents was observed to
yield the best rutin solubilities. Because of the acidic properties of rutin, the
presence of basic sites on the components of the NADES generally leads to
enhanced solubility.
PMID- 29951829
TI - Correction to: A systematic review of patient perspectives on surveillance after
colorectal cancer treatment.
AB - The original version of this article unfortunately contained a mistake. The
online supplementary files are missing. The complete version of online
supplementary materials are published with this erratum.
PMID- 29951828
TI - IGF2 and IGF1R identified as novel tip cell genes in primary microvascular
endothelial cell monolayers.
AB - Tip cells, the leading cells of angiogenic sprouts, were identified in cultures
of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker.
Here, we show that tip cells are also present in primary human microvascular
endothelial cells (hMVECs), a more relevant endothelial cell type for
angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is
shown that endothelial cell cultures contain a dynamic population of CD34+ cells
with many hallmarks of tip cells, including filopodia-like extensions, elevated
mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF
and inhibition by DLL4. Furthermore, we demonstrate that our in vitro tip cell
model can be exploited to investigate cellular and molecular mechanisms in tip
cells and to discover novel targets for anti-angiogenesis therapy in patients.
Small interfering RNA (siRNA) was used to knockdown gene expression of the known
tip cell genes angiopoietin 2 (ANGPT2) and tyrosine kinase with immunoglobulin
like and EGF-like domains 1 (TIE1), which resulted in similar effects on tip
cells and sprouting as compared to inhibition of tip cells in vivo. Finally, we
identified two novel tip cell-specific genes in CD34+ tip cells in vitro: insulin
like growth factor 2 (IGF2) and IGF-1-receptor (IGF1R). Knockdown of these genes
resulted in a significant decrease in the fraction of tip cells and in the extent
of sprouting in vitro and in vivo. In conclusion, this study shows that by using
our in vitro tip cell model, two novel essential tip cells genes are identified.
PMID- 29951830
TI - Transcatheter Mitral Valve Replacement: Functional Requirements for Device
Design, Bench-Top, and Pre-Clinical Evaluation.
AB - Transcatheter Mitral Valve Replacement (TMVR) is currently under clinical
investigation as a viable treatment option for mitral regurgitation (MR).
Therefore, it is important to outline the key functional requirements of a TMVR
prosthesis in order to provide an overall approach to assessing mitral valve
replacement devices utilizing a combination of in vitro and preclinical methods.
This article provides a review of the mitral valve disease as well as general
considerations and guidance for developing a TMVR device based on International
Industry Standards. Specific details pertaining to the mitral valve apparatus,
morphology of mitral valve disease, assessment of specific patient population as
well as hazard analysis to evaluate and develop a TMVR device to treat a specific
patient population have been included. The details contained within this report
are not all inclusive or explicate for every technology being developed but
rather thought of as a general guide on how a TMVR technology could be developed
in alignment with International Industry Standards. Key learnings from the
Transcatheter Aortic Valve Replacement (TAVR) experience has also been considered
and taken into account when outlining this general guidance for TMVR. Key
learning points from the TAVR development experience included the following:
quantification of acceptable levels of paravalvular leak, valve migration
potential using various anchoring methods and overall implant frame failure modes
when treating the native aortic valve. It should be noted that TAVR is over a
decade further along in development and clinical experience compared to TMVR.
These key learnings from the early experience with TAVR should be considered with
all transcatheter development projects.
PMID- 29951831
TI - Novel Approaches for the Management of AL Amyloidosis.
AB - PURPOSE OF REVIEW: Light-chain-associated (AL) amyloidosis is a rare disease with
a poor prognosis. However, we have made recent strides in more accurate diagnosis
and effective treatment. Here, we discuss the most recent updates and
advancements during the past year in the diagnosis, prognostication, and
management of AL amyloidosis both in the upfront and relapsed setting. RECENT
FINDINGS: New imaging modalities, such as cardiac magnetic resonance (CMR) and
use of fluorine-labeled radiotracers, are emerging as an important diagnostic
tool in conjunction with biomarkers in the diagnosis, prognosis, and monitoring
of the effects of therapy. In addition, ongoing evaluation of plasma cell
directed therapeutics, including daratumumab, pomalidomide, and ixazomib, as well
as promising targeted novel therapies, such as the monoclonal antibody NEOD001,
are in development. In conclusion, incorporating the use of plasma cell-directed
therapy and novel agents targeting the amyloid deposits itself hold enormous
potential in achieving improved outcomes in AL amyloidosis.
PMID- 29951832
TI - [Endovascular stroke treatment in nonagenarians].
PMID- 29951833
TI - [Influenza: special aspects in old age].
AB - In Germany up to 20% of the population are affected by influenza every year.
Particularly for the elderly, influenza is related to high morbidity and
mortality and 90% of deaths are related to the group of 60 years and older. In
this context, seasonal influenza caused by influenza A (H3N2) viruses is
exceedingly relevant for the elderly. The aging of the immune system,
immunosenescence, is well documented as the cause of increased susceptibility to
infection and change of typical symptoms. This can cause a delay in diagnosing
and treatment of influenza infections. Furthermore, immunosenescence can lead to
decreased efficacy of vaccination. Adjuvanted vaccines and vaccines with higher
antigen content cause an enhanced immune response and are therefore especially
suitable for prevention. The Standing Vaccination Committee (STIKO) recommends
vaccination against seasonal influenza for all persons 60 years of age and over
as well as for nursing home residents, pregnant women and chronically ill
patients. For the coming influenza season 2018/19, the STIKO generally recommends
the administration of quadrivalent (tetravalent) vaccines for the first time.
PMID- 29951834
TI - [Journal Club].
PMID- 29951835
TI - Normal pancreatic parenchymal thickness by CT in healthy children.
AB - BACKGROUND: Chronic pancreatitis is increasingly recognized in the pediatric
population. Atrophy is an important, but qualitative, finding of chronic
pancreatitis. To transition to a quantitative measure that can specifically
define atrophy requires knowledge of normal pancreatic parenchymal bulk in
children. OBJECTIVE: The purpose of this study was to define normal pancreatic
thickness (linear measurements) at multiple anatomic locations in the pancreas of
healthy children. MATERIALS AND METHODS: This was an Institutional Review Board
approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant
retrospective study. Three reviewers measured the thickness of the pancreas at
four locations (head, neck, body, tail) on computed tomography (CT) examinations
performed with intravenous contrast in children without a history of pancreatic
disease. Measurements were made on 140 examinations, evenly distributed among 7
age groups (3-16.99 years) with 10 males and 10 females in each group. Agreement
and bias between reviewers were assessed by intra-class correlation coefficients
(ICC) and Bland-Altman analyses. Correlation with age, height and weight were
assessed with Spearman's rho (rho). RESULTS: The mean (for 3 readers) thicknesses
of the head, neck, body and tail were 1.3-2 cm, 0.7-1 cm, 0.9-1.6 cm and 1-1.6
cm, respectively, depending on patient age. Measurement agreement between
reviewers was fair to good (ICC: 0.52-0.7). Bias between reviewers ranged from 0
to 3 mm. Pancreatic thickness was weakly to moderately correlated with age
(rho=0.39-0.52), height (rho=0.44-0.61) and weight (rho=0.51-0.64). CONCLUSION:
We have defined normal ranges for thickness of the pancreas at four locations,
and have shown that these measurements depend on patient age and size. These data
may be useful to more objectively define pancreatic atrophy in children with
suspected pancreatic disease.
PMID- 29951836
TI - Real-time ultrasound-guided pigtail catheter chest drain for complicated
parapneumonic effusion and empyema in children - 16-year, single-centre
experience of radiologically placed drains.
AB - BACKGROUND: Chest tube drainage with fibrinolytics is a cost-effective treatment
option for parapneumonic effusion and empyema in children. Although the
additional use of ultrasound (US) guidance is recommended, this is rarely
performed in real time to direct drain insertion. OBJECTIVE: To evaluate the
effectiveness and safety of real-time US-guided, radiologically placed chest
drains at a tertiary university hospital. MATERIALS AND METHODS: This was a
retrospective review over a 16-year period of all children with parapneumonic
effusion or empyema undergoing percutaneous US-guided drainage at our centre.
RESULTS: Three hundred and three drains were placed in 285 patients. Treatment
was successful in 93% of patients after a single drain (98.2% success with 2 or 3
drains). Five children had peri-insertion complications, but none was
significant. The success rate improved with experience. Although five patients
required surgical intervention, all children treated since 2012 were successfully
treated with single-tube drainage only and none has required surgery. CONCLUSION:
Our technique for inserting small-bore (<=8.5 F) catheter drains under US
guidance is effective and appears to be a safe procedure for first-line
management of complicated parapneumonic effusion and empyema.
PMID- 29951837
TI - Two paths diverged in the stroma: targeting to dual SEC translocase systems in
chloroplasts.
AB - Chloroplasts inherited systems and strategies for protein targeting,
translocation, and integration from their cyanobacterial ancestor. Unlike
cyanobacteria however, chloroplasts in green algae and plants contain two
distinct SEC translocase/integrase systems: the SEC1 system in the thylakoid
membrane and the SEC2 system in the inner envelope membrane. This review
summarizes the mode of action of SEC translocases, identification of components
of the SEC2 system, evolutionary history of SCY and SECA genes, and previous work
on the co- and post-translational targeting of lumenal and thylakoid membrane
proteins to the SEC1 system. Recent work identifying substrates for the SEC2
system and potential features that may contribute to inner envelope targeting are
also discussed.
PMID- 29951838
TI - Critical Roles of microRNAs in the Pathogenesis of Fatty Liver: New Advances,
Challenges, and Potential Directions.
AB - In this review, we summarize the current understanding of microRNA (miRNA)
mediated modulation of the gene expression in the fatty liver as well as related
signaling pathways. Because of the breadth and diversity of miRNAs, miRNAs may
have a very wide variety of biological functions, and much evidence has confirmed
that miRNAs are involved in the pathogenesis of fatty liver. In the
pathophysiological mechanism of fatty liver, miRNAs may be regulated by upstream
regulators, and have their own regulatory targets. miRNAs display important roles
in the pathological mechanisms of alcoholic liver disease and non-alcoholic fatty
liver disease. At present, most of the miRNA studies are focused on cell and
tissue levels, and in vivo studies will help us elucidate the regulation of
miRNAs and help us evaluate the potential of miRNAs as diagnostic markers and
therapeutic targets. Furthermore, there is evidence that miRNAs are involved in
the mechanism of natural medicine treatment in fatty liver. Given the important
roles of miRNAs in the pathogenesis of fatty liver, we predict that studies of
miRNAs in the pathogenesis of fatty liver will contribute to the elucidation of
fatty liver pathology and the treatment of fatty liver patients.
PMID- 29951839
TI - Hostile pelvis: how to avoid permanent stoma.
AB - The aim was to report our experience with delayed colo-anal anastomosis (DCA) to
avoid permanent stoma for complex rectal cases evaluating short- and long-term
outcomes. Nine patients who underwent DCA from 2011 to 2016 were collected and
analysed case by case. We considered medical history and surgical outcomes. Long
term bowel function was evaluated using the Wexner and low anterior resection
syndrome (LARS) score at 6, 12 and 24 months. The range from previous surgery and
salvage procedure was 337 days. All cases were performed with a full laparoscopic
approach. The median length of hospital stay was 15 days. The median follow-up
was 970.5 days. There was no peri-operative mortality. Two patients developed a
post-operative pelvic abscess that required redo surgery. Long-term post
operative complications were mucosal prolapsed, anastomosis retraction and
anastomotic stricture. The average values of LARS and Wexner scores were,
respectively, at 6 months 33.7 and 16.2, at 12 months 28.5 and 11.7, at 24 months
21.1 and 6.7. Colo-anal sleeve delayed anastomosis appears a real answer to avoid
permanent stoma in selected patients. The laparoscopic procedure is safe and
feasible for skilful mini-invasive surgeons. Our experience describes the
complexity of clinical history of these patients underlying a slow, but
progressive improvement in continence after restoration of bowel continuity.
PMID- 29951840
TI - The effect of pulmonary hypertension on inpatient outcomes of laparoscopic
procedures.
AB - The purpose of our analysis was to assess the effects of pulmonary hypertension
(PH) on clinical outcomes of patients undergoing laparoscopic procedures.
Pulmonary hypertension alters physiologic patterns that has the potential to
complicate laparoscopic procedures, however, an in-depth analysis evaluating
survival outcomes, complications, and associated comorbidities has not been done
before. Data from the National Inpatient Survey were used to identify 179,663
patients without PH and 1453 patients with PH undergoing laparoscopic procedures
from the years 2003-2013. In patients with pulmonary hypertension, the presence
of the following comorbidities, congestive heart failure (OR 3.56) diabetes with
chronic complications (OR 3.74) fluid and electrolyte disorders (OR 7.34)
metastatic cancer (OR 14.42) and peripheral vascular disease (OR 3.12) increased
in-patient mortality. In regards to post-operative complications, patients with
PH were more likely to have cardiac complications defined as cardiac arrest,
cardiac insufficiency, cardiorespiratory failure, or heart failure (OR 3.74).
Patients with PH were also more likely to develop iatrogenic pneumothorax (OR
4.13) iatrogenic pulmonary embolism (OR 7.65) and post-operative urinary
complications (OR 1.92). Overall, the comorbidity with the highest association
with in-patient mortality was metastatic cancer and of all complications,
patients with PH were most likely to develop iatrogenic pulmonary embolism.
Preparing for these adversities, notably in patients with certain associated
conditions has the potential to improve patient outcome.
PMID- 29951841
TI - Analysis of Fragmentation Pathways of New-Type Synthetic Cannabinoids Using
Electrospray Ionization.
AB - Recently, dozens of new psychoactive substances have appeared on the European
drug market every year. The most abundant group of these compounds is synthetic
cannabinoids. In the first few years of the "legal highs" phenomenon, JWH (John
W. Huffman) compounds were especially popular among drug users. However, the
group of synthetic cannabinoids is constantly expanding, as new compounds are
created by replacing known structural elements with different chemical groups.
The problem with the identification of novel substances in forensic laboratories
results from the structural similarity of the compounds and the rapid
introduction of newer designer drugs on the black market. In this study, the
fragmentation patterns of 29 new-type synthetic cannabinoids using electrospray
ionization were investigated. The analysis was performed using quadrupole time-of
flight mass spectrometry. Based on measurements carried out under various
conditions, the way of fragmentation of the tested compounds that were divided
into groups due to their chemical structure was established. The study showed
that the bond between the carbon atom of the carbonyl group and the ring or NH
group attached to the ring was mainly cleaved. This mechanism was adequate for
the fragmentation of first-generation synthetic cannabinoids. This paper presents
characteristic ions formed by synthetic cannabinoids (i.e., ions originating from
an indole/indazole ring and an adamanyl/naphthalene/quinoline ring) using
electrospray ionization. Knowledge of these specific fragments can be used in
forensic laboratories to determine the structure of novel compounds from the
group of synthetic cannabinoids. Graphical Abstract ?.
PMID- 29951842
TI - Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the
Cobalt and Manganese Metal Binding of alpha-Synuclein Protein.
AB - Structural characterization of intrinsically disordered proteins (IDPs) has been
a major challenge in the field of protein science due to limited capabilities to
obtain full-length high-resolution structures. Native ESI-MS with top-down MS was
utilized to obtain structural features of protein-ligand binding for the
Parkinson's disease-related protein, alpha-synuclein (alphaSyn), which is
natively unstructured. Binding of heavy metals has been implicated in the
accelerated formation of alphaSyn aggregation. Using high-resolution Fourier
transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS
with various fragmentation methods, including electron capture dissociation
(ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS3),
deduced the binding sites of cobalt and manganese to the C-terminal region of the
protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of
alphaSyn upon metal binding. The combination of native top-down MS and IM-MS
provides structural information of protein-ligand interactions for intrinsically
disordered proteins. Graphical Abstract ?.
PMID- 29951843
TI - Characterization and genomic analysis of highly efficient thermotolerant oil
degrading bacterium Gordonia sp. 1D.
AB - A thermotolerant bacterial strain 1D isolated from refinery oil-contaminated soil
was identified as Gordonia sp. based on the analysis of 16S rRNA and gyrB gene
sequences. The strain was found to utilize crude oil, diesel fuel, and a wide
spectrum of alkanes at temperatures up to 50 degrees C. Strain 1D is the first
representative of Gordonia amicalis capable of utilizing alkanes of chain length
up to S36 at a temperature of 45-50 degrees C. The degree of crude oil
degradation by Gordonia sp. 1D at 45 degrees C was 38% in liquid medium and 40%
in soil (with regard to abiotic loss). There are no examples of so effective
hydrocarbon-oxidizing thermotolerant Gordonia in the world literature. The 1D
genome analysis revealed the presence of two alkane hydroxylase gene clusters,
genes of dibenzothiophene cleavage, and the cleavage of salicylate and gentisate
naphthalene metabolism intermediates. The highly efficient thermotolerant strain
Gordonia sp. 1D can be used in remediation of oil-contaminated soils in hot
climates.
PMID- 29951844
TI - Recent advances in metal-organic frameworks for adsorption of common aromatic
pollutants.
AB - This review (with 85 refs.) summarizes the recent literature on the adsorption of
common aromatic pollutants by using modified metal-organic frameworks (MOFs).
Four kinds of aromatic pollutants are discussed, namely benzene homologues,
polycyclic aromatic hydrocarbons (PAHs), organic dyes and their intermediates,
and pharmaceuticals and personal care products (PPCPs). MOFs are shown to be
excellent adsorbents that can be employed to both the elimination of pollutants
and to their extraction and quantitation. Adsorption mechanisms and interactions
between aromatic pollutants and MOFs are discussed. Finally, the actual
challenges of existence and the perspective routes towards future improvements in
the field are addressed. Graphical abstract Recent advance on adsorption of
common aromatic pollutants including benzene series, polycyclic aromatic
hydrocarbons, organic dyes and their intermediates, pharmaceuticals and personal
care products by metal-organic frameworks.
PMID- 29951846
TI - Health-related outcomes of critically ill patients with and without sepsis.
AB - PURPOSE: To determine differences in health-related quality of life (HRQoL),
survival and healthcare resource use of critically ill adults with and without
sepsis. METHODS: We conducted a primary propensity score matched analysis of
patients with and without sepsis enrolled in a large multicentre clinical trial.
Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and
hospital admission and cost of ICU and hospital treatment to 2 years. RESULTS: We
obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched
806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After
matching, there were no significant differences in the proportion of survivors
with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p =
0.86), self-care (24.7% vs. 26.0%, p = 0.44), usual activities (44.5% vs. 46.8%,
p = 0.28), pain/discomfort (42.4% vs. 41.6%, p = 0.54) and anxiety/depression
(36.9% vs. 37.7%, p = 0.68). There was no significant difference in survival at 2
years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86-1.18, p = 0.94).
The initial ICU and hospital admission were longer for patients with sepsis: 10.1
+/- 11.9 vs. 8.0 +/- 9.8 days (p < 0.0001) and 22.8 +/- 21.2 vs. 19.1 +/- 19.0
days, (p = 0.0003) respectively. The cost of ICU admissions was higher for
patients with sepsis: A$43,345 +/- 46,263 (?35,109 +/- 35,043) versus 34,844 +/-
38,281 (?28,223 +/- 31,007), mean difference $8501 (?6885), 95% CI $4342-12,660
(?3517 +/- 10,254), p < 0.001 as was the total cost of hospital treatment to 2
years: A$74,120 +/- 60,750 (?60,037 +/- 49,207) versus A$65,806 +/- 59,856
(?53,302 +/- 48,483), p = 0.005. CONCLUSIONS: Critically ill patients with sepsis
have higher healthcare resource use and costs but similar survival and HRQoL
compared to matched patients without sepsis.
PMID- 29951845
TI - Characterization of the pheophorbide a oxygenase/phyllobilin pathway of
chlorophyll breakdown in grasses.
AB - MAIN CONCLUSION: Although the PAO/phyllobilin pathway of chlorophyll breakdown is
active in grass leaf senescence, the abundance of phyllobilins is far below the
amount of degraded chlorophyll. The yellowing of fully developed leaves is the
most prominent visual symptom of plant senescence. Thereby, chlorophyll is
degraded via the so-called pheophorbide a oxygenase (PAO)/phyllobilin pathway to
a species-specific set of phyllobilins, linear tetrapyrrolic products of
chlorophyll breakdown. Here, we investigated the diversity and abundance of
phyllobilins in cereal and forage crops, i.e. barley, rice, ryegrass, sorghum and
wheat, using liquid chromatography-mass spectrometry. A total of thirteen
phyllobilins were identified, among them four novel, not yet described ones,
pointing to a rather high diversity of phyllobilin-modifying activities present
in the Gramineae. Along with these phyllobilins, barley orthologs of known
Arabidopsis thaliana chlorophyll catabolic enzymes were demonstrated to localize
in the chloroplast, and two of them, i.e. PAO and pheophytin pheophorbide
hydrolase, complemented respective Arabidopsis mutants. These data confirm
functionality of the PAO/phyllobilin pathway in grasses. Interestingly, when
comparing phyllobilin abundance with amounts of degraded chlorophyll in senescent
leaves, in most analyzed grass species only minor fractions of chlorophyll were
recovered as phyllobilins, opposite to A. thaliana where phyllobilin quantities
match degraded chlorophyll rather well. These data show that, despite the
presence and activity of the PAO/phyllobilin pathway in barley (and other
cereals), phyllobilins do not accumulate stoichiometrically, implying possible
degradation of chlorophyll beyond the phyllobilin level.
PMID- 29951847
TI - In Vivo Mapping and Quantification of Creatine Using Chemical Exchange Saturation
Transfer Imaging in Rat Models of Epileptic Seizure.
AB - PURPOSE: To evaluate signal changes in the hippocampus of epileptic seizure rat
models, based on quantified creatine chemical exchange saturation transfer
(CrCEST) signals. PROCEDURES: CEST data and 1H magnetic resonance spectroscopy
(1H MRS) data were obtained for the two imaging groups: control (CTRL) and
epileptic seizure-induced (ES; via kainic acid [KA] injection) groups. CrCEST
signals in the hippocampal regions were quantitatively evaluated; correlations
between CrCEST signals and phosphocreatine (PCr) and total creatine (tCr; PCr +
Cr) concentrations, derived from the analysis of 1H MRS data, were investigated
as a function of time changes (before KA injection, 3 and 5 h after KA
injection). RESULTS: Measured CrCEST signals were exhibited significant
differences between before and after KA injection in the ES group. At each time
point, CrCEST signals showed significant correlations with PCr concentration (all
|r| > 0.59; all P < 0.05); no significant correlations were found between CrCEST
signals and tCr concentrations (all |r| < 0.22; all P > 0.05). CONCLUSIONS:
CrCEST can adequately detect changes in the concentration of Cr as a result of
energy metabolism, and may serve as a potentially useful tool for diagnosis and
assessment of prognosis in epilepsy.
PMID- 29951848
TI - Correction to: Improving Dengue Diagnostics and Management Through Innovative
Technology.
AB - In the original publication, the Table 2 contains an error. The original article
has been corrected.
PMID- 29951849
TI - Author's reply to the Letter to the Editor for "Efficacy and safety of metallic
stents in comparison to plastic stents for endoscopic drainage of peripancreatic
fluid collections: a meta-analysis and trial sequential analysis".
PMID- 29951850
TI - Effects of physical activity on cognitive performance: a controlled clinical
study in depressive patients.
AB - Physical activity is a common adjunctive therapy in psychiatric and psychosomatic
hospitals. In the present study, we assessed the effects of an exercise program,
integrated into routine inpatient treatment, on cognitive performance and
subjective severity of depression in a sample of patients suffering from major
depression. We randomized n = 38 patients with unipolar depression to either
physical exercise (n = 18) or occupational therapy as an active control treatment
(n = 20). Both treatments were delivered in group format over a period of 3-4
weeks. Data indicate that there were significant improvements of cognitive
functions and depressive symptoms in both groups, with specific treatment effects
in reaction time and in short-term verbal memory favoring the physical activity
group. In conclusion, we found physical exercise to be a feasible, easy-to
implement add-on therapy for depressive patients with promising effects on
cognitive performance. However, these results need to be replicated in larger
samples with an extended follow-up.
PMID- 29951851
TI - Water quality observations in the marine aquaculture complex of the Deeba
Triangle, Lake Manzala, Egyptian Mediterranean coast.
AB - Coastal aquaculture is faced with extreme variation in water quality. The Deeba
Triangle on Lake Manzala is the largest marine coastal aquaculture-producing area
on the Egyptian Mediterranean. Samples from 16 ponds were taken during four
seasons (2014-2015), to investigate the variation of 12 water quality parameters
at that region. We tested the hypothesis that there is no spatial or temporal
variation in water quality of the fish ponds. Fish ponds were statistically
clustered into three groups (p = 0.0005) coincident with their geographical
location. Hypersaline and transparent waters characterized the western ponds;
higher dissolved oxygen and higher nutrients characterized the central region.
These spatial differences were principally due to variations in salinity and
nutrients of the water sources used for irrigation of the ponds and to
differences in the aeration management styles. Strong seasonality was seen in
water temperature (following air temperature), nutrients, and turbidity
(following the seasonal cycles of various water sources from the Lake Manzala and
the seasonality of the petrochemical plants effluents close to these ponds). We
conclude that municipal effluents significantly affected, spatially and
temporally, the quality of the irrigation water used for coastal aquaculture
purposes, which consequently might affect fish yield.
PMID- 29951852
TI - [Alpha-Gal-associated delayed red meat anaphylaxis as an occupational disease].
AB - In a 30-year-old chef with recurrent delayed angioedema history as well as the
experimental detection of IgE antibodies against galactose-alpha-(1,3)-galactose
(alpha-Gal) pointed to alpha-Gal as the causative agent. The diagnosis,
therefore, was delayed anaphylaxis due to alpha-Gal. Because of the potential
relationship to his profession, we submitted a dermatologist's report BK 5101 to
the liability and insurance association, whereupon his contract of employment was
terminated without notice. As a consequence, we reported an occupational disease.
This case demonstrates an underdiagnosed, potentially life-threatening allergy to
the disaccharide alpha-Gal in red meat as an occupational disease.
PMID- 29951854
TI - On species richness and rarefaction: size- and coverage-based techniques quantify
different characteristics of richness change in biodiversity.
AB - Changes in biodiversity today shape the future patterns of biodiversity. This
fact underlines the importance of understanding changes in biodiversity through
time and space. The number of species, known as species richness, has long been
studied as a key indicator that quantifies the state of biodiversity, and
standardisation techniques, called rarefaction, have also been used to undertake
a fair comparison of the richness observed at different times or locations. The
present study asks whether utilising different rarefaction techniques attains
comparable results when investigating changes in species richness. The study
framework presents the statistical nature of two commonly adopted rarefaction
techniques: size-based and coverage-based rarefaction. The key finding is that
the rarefied richness results calculated by these two different rarefaction
methods reflect different aspects of biodiversity change, the shift in community
size and/or composition. This fact illuminates that richness analyses based on
different rarefaction techniques can reach different conclusions that may be
contradictory. The study also investigates the mechanism creating such
divergence. As such, special care is required when evaluating biodiversity change
using species richness as an indicator.
PMID- 29951853
TI - [S1 guideline on intermittent pneumatic compression (IPC)].
AB - Under the direction of the German Society of Phlebology (Deutsche Gesellschaft
fur Phlebologie) and in cooperation with other specialist associations, the S1
guideline on intermittent pneumatic compression (IPC) was adopted in January
2018. It replaces the previous guideline from March 2005. The aim of the
guideline is to optimize the indication and therapeutic use of IPC in vascular
diseases and edema. An extensive literature search of MEDLINE, existing
guidelines, and work relevant to the topic was performed. In view of the often
methodologically weak study quality with often small numbers of cases and
heterogeneous treatment protocols, recommendations can often only be derived from
the available data using good clinical practice/expert consensus. Intermittent
pneumatic compression is used for thromboembolism prophylaxis, decongestive
therapy for edema, and to positively influence arterial and venous circulation to
improve clinical symptoms and accelerate ulcer healing in both the outpatient and
inpatient care setting. The therapy regimens and devices used depend on the
indication and target location. They can be used as outpatient and inpatient
devices as well as at home for long-term indications. A target indication is
thrombosis prophylaxis. IPC should be used in severe chronic venous insufficiency
(stages C4b to C6), in extremity lymphedema as an add-on therapy and in
peripheral arterial occlusive disease (PAOD) with stable intermittent
claudication or critical ischemia. IPC can be used in post-traumatic edema,
therapy-resistant venous edema, lipedema and hemiplegia with sensory deficits and
edema. Absolute and relative contraindications to IPC must be taken into account
and risks considered and avoided as far as possible. Adverse events are extremely
rare if IPC is used correctly. If the indication and application are correct-also
as an add-on therapy-it is a safe and effective treatment method, especially for
the treatment of the described vascular diseases and edema as well as thrombosis
prophylaxis.
PMID- 29951855
TI - Reconstructing gene trees from Fitch's xenology relation.
AB - Two genes are xenologs in the sense of Fitch if they are separated by at least
one horizontal gene transfer event. Horizonal gene transfer is asymmetric in the
sense that the transferred copy is distinguished from the one that remains within
the ancestral lineage. Hence xenology is more precisely thought of as a non
symmetric relation: y is xenologous to x if y has been horizontally transferred
at least once since it diverged from the least common ancestor of x and y. We
show that xenology relations are characterized by a small set of forbidden
induced subgraphs on three vertices. Furthermore, each xenology relation can be
derived from a unique least-resolved edge-labeled phylogenetic tree. We provide a
linear-time algorithm for the recognition of xenology relations and for the
construction of its least-resolved edge-labeled phylogenetic tree. The fact that
being a xenology relation is a heritable graph property, finally has far-reaching
consequences on approximation problems associated with xenology relations.
PMID- 29951856
TI - A short voyage into the past: former misconceptions and misinterpretations in the
etiology of some viral diseases.
AB - The advancement of human knowledge has historically followed the pattern of one
step growth (the same pattern followed by microorganisms in laboratory culture
conditions). In this way, each new important discovery opened the door to
multiple secondary breakthroughs, eventually reaching a "plateau" when new
findings emerged. Microbiology research has usually followed this pattern, but
often the conclusions attained from experimentation/observation were either
equivocal or altogether false, causing important delays in the advancement of
this science. This mini-review deals with some of these documented scientific
errors, but the aim is not to include every mistake, but to select those that are
paramount to the advance of Microbiology.
PMID- 29951857
TI - Novel strategy for expression of authentic and bioactive human basic fibroblast
growth factor in Bacillus subtilis.
AB - Inteins, also known as "protein introns," have been found to be present in many
microbial species and widely employed for the expression and purification of
recombinant proteins in Escherichia coli. However, interestingly, until now there
has not been much information on the identification and application of inteins to
protein expression in Bacillus subtilis. In this article, for the first time,
despite the likelihood of absence of inteins in B. subtilis, this bacterium was
shown to be able to facilitate auto-catalytic cleavages of fusions formed between
inteins and recombinant proteins. Employing a construct expressing the intein,
Ssp DnaB, (DnaB), which was fused at its N-terminus with the cellulose-binding
domain (CellBD) of an endoglucanase encoded by the cenA gene of Cellulomonas
fimi, the construct was demonstrated to be capable of mediating intracellular
expression of basic fibroblast growth factor (bFGF), followed by auto-processing
of the CellBD-DnaB-bFGF fusion to result in bFGF possessing the 146-residue
authentic structure. The mentioned fusion was shown to result in a high yield of
84 mg l-1 of biologically active bFGF. Future work in improving the growth of B.
subtilis may enable the use of this bacterium, working in cooperation with
inteins, to result in a new platform for efficient expression of valuable
proteins.
PMID- 29951858
TI - Polyhydroxybutyrate (PHB) biodegradation using bacterial strains with
demonstrated and predicted PHB depolymerase activity.
AB - The biodegradation of polyhydroxybutyrate (PHB) has been broadly investigated,
but studies typically focus on a single strain or enzyme and little attention has
been paid to comparing the interaction of different PHB depolymerase (PhaZ)
producing strains with this biopolymer. In this work, we selected nine bacterial
strains-five with demonstrated and four with predicted PhaZ activity-to compare
their effectiveness at degrading PHB film provided as sole carbon source. Each of
the strains with demonstrated activity were able to use the PHB film (maximum
mass losses ranging from 12% after 2 days for Paucimonas lemoignei to 90% after 4
days for Cupriavidus sp.), and to a lower extent Marinobacter algicola DG893
(with a predicted PhaZ) achieved PHB film mass loss of 11% after 2 weeks of
exposure. Among the strains with proven PhaZ activity, Ralstonia sp. showed the
highest specific activity since less biomass was required to degrade the polymer
in comparison to the other strains. In the case of Ralstonia sp., PHB continued
to be degraded at pH values as low as pH 3.3-3.7. In addition, analysis of the
extracellular fractions of the strains with demonstrated activity showed that
Comamonas testosteroni, Cupriavidus sp., and Ralstonia sp. readily degraded both
PHB film and PHB particles in agar suspensions. This study highlights that whole
cell cultures and enzymatic (extracellular) fractions display different levels of
activity, an important factor in the development of PHB-based applications and in
understanding the fate of PHB and other PHAs released in the environment.
Furthermore, predictions of PhaZ functionality from genome sequencing analyses
remain to be validated by experimental results; PHB-degrading ability could not
be proven for three of four investigated species predicted by the
polyhydroxyalkanoates (PHA) depolymerase engineering database.
PMID- 29951859
TI - Multiple genetic tools for editing the genome of Riemerella anatipestifer using a
counterselectable marker.
AB - Riemerella anatipestifer (R. anatipestifer, RA) is an important bacterial
pathogen of ducks and other birds; infection with RA causes high poultry
mortality and heavy economic losses in the poultry industry. However, the
pathogenesis of this bacterium is poorly understood, in part due to the lack of a
suitable array of methods for genetic manipulation. In this study, we first
examined the efficacy of the mutated pheS gene (pheS*) as a counterselectable
marker in R. anatipestifer. A suicide vector carrying pheS*, pOES, was
constructed and used for markerless deletion of the gene RA0C_2053 which encode a
putative TonB-dependent receptor in RA ATCC11845. The suicide plasmid pOES was
also used to introduce a "knock-in" Myc-tag into the C-terminus of RA0C_1912
which encode a putative Fur protein. Using pheS* as a counterselectable marker,
markerless mutagenesis and "knock-in" genetic manipulation techniques were also
developed based on natural transformation. Furthermore, this marker was used to
generate a point mutation in the RA0C_1912 gene of the RA ATCC11845 genome. The
genetic methods developed in this study provide new and useful tools required to
investigate the physiology and pathogenic mechanisms of this bacterium. These
techniques may also have wider application in many other members of the
Flavobacteria.
PMID- 29951860
TI - Diallyl disulfide from garlic oil inhibits Pseudomonas aeruginosa virulence
factors by inactivating key quorum sensing genes.
AB - Garlic oil can disrupt the quorum sensing (QS) pathways of the opportunistic
pathogen Pseudomonas aeruginosa; however, the underlying mechanisms for this
effect are unclear. Diallyl disulfide (DADS) is one of the most abundant sulfur
containing compounds in garlic oil. This study investigated the effects of DADS
on the growth, virulence factor production (elastase, pyocyanin, biofilm, and
swarming motility), and essential gene expression of P. aeruginosa PAO1,
particularly as they apply to QS and virulence. DADS at 1.28 mg/mL did not affect
P. aeruginosa PAO1 growth, although it decreased elastase and pyocyanin
production, biofilm formation, and swarming motility. Each of these phenomena is
regulated by the three QS systems of P. aeruginosa PAO1 (las, rhl, and pqs). Real
time q-PCR revealed that DADS down-regulated the transcription levels of several
important QS genes (lasI, lasR, rhlI, rhlR, pqsA, and pqsR) in the three systems.
Furthermore, the transcription levels of QS-regulated virulence genes were also
down-regulated. The lasB gene, encoding LasB elastase, is co-regulated by the
las, rhl, and pqs systems, and thus the down-regulation of genes across the three
systems further down-regulated lasB. Additionally, phzM (encoding pyocyanin),
pslB (responsible for the production of a biofilm matrix polysaccharide), and
chiC (encoding chitinase) were positively activated by LasR, and a decrease in
lasR transcription further down-regulated the transcription of phzM, pslB, and
chiC. Hence, DADS inhibits P. aeruginosa PAO1 virulence factors by inactivating
the transcription of key genes across three different QS systems.
PMID- 29951861
TI - [What the rheumatologist can learn from the dermatologist-or: nobody can separate
good friends : Interfaces of both domains].
AB - BACKGROUND: Rheumatology and dermatology are two medical disciplines, which are
closely interwoven with each other. RESULTS: Frequent direct areas of cooperation
are with psoriasis, psoriatic arthritis, connective tissue diseases and
vasculitis. As a whole, chronic inflammatory diseases are frequently associated
with cutaneous manifestations and require a specialized dermatological treatment.
The diagnosis and treatment of adverse cutaneous reactions to systemic
rheumatological treatment creates an additional area requiring a collaborative
effort. CONCLUSION: The close cooperation between rheumatology and dermatology
clinics, beeing established in many institutions, has many advantages for our
patients, especially in those with a complex course of the disease. Furthermore,
it presents a valuable opportunity to learn from each other. The successful
establishment of inflammation centers in some larger hospitals is proof for the
development of an intensified interdisciplinary treatment of patients.
PMID- 29951862
TI - 18O-labeled phosphate applied to soil appears in the shoots of maize after uptake
by roots but not after uptake by an arbuscular mycorrhizal fungus.
AB - The application of 33P or 32P isotopes to directly trace phosphorus (P) uptake
during arbuscular mycorrhizal (AM) symbiosis is limited by the radioactivity of
the two P isotopes, especially under field conditions. A potential alternative
method for tracing P uptake in plant-soil systems relies on the analysis of the
stable oxygen (O) isotopes of ortho-phosphate (Pi); however, little is known
about the fate of the P-O bond during Pi uptake in AM symbioses. This study
investigated whether the abundance of 18O in Pi extracted from the shoots of
maize increased after 18O-labeled Pi added to soil was taken up by either roots
of maize or AM extraradical hyphae. A two-compartment culture system, consisting
of a root and AM hyphal compartment (RHC, including both roots and AM hyphae) and
an AM hyphal compartment (HC, including only hyphae) was designed, and the AM
fungus Funneliformis mosseae was used to inoculate the roots of maize. Our
results indicated that the abundance of 18O in Pi extracted from the maize shoots
increased significantly 3 months after the addition of 18O-labeled Pi to the soil
in the pots which only contained roots. The abundance of 18O was much lower than
expected, however, which suggests a great majority of 18O in labeled Pi was lost
in the soil or during Pi metabolism in the shoots of maize. The abundance of 18O
in Pi extracted from the maize shoots did not increase 3 months after 18O-labeled
Pi was added to the HC, and therefore, loss of 18O in labeled Pi may also occur
during Pi metabolism in AM hyphae. Use of 18O-labeled Pi as a qualitative tracer
of P uptake during AM symbiosis appears unfeasible for such a long-term (3
months) experiment, although it should be investigated in a short-term labeling
experiment.
PMID- 29951863
TI - Utilization of organic nitrogen by arbuscular mycorrhizal fungi-is there a
specific role for protists and ammonia oxidizers?
AB - Arbuscular mycorrhizal (AM) fungi can significantly contribute to plant nitrogen
(N) uptake from complex organic sources, most likely in concert with activity of
soil saprotrophs and other microbes releasing and transforming the N bound in
organic forms. Here, we tested whether AM fungus (Rhizophagus irregularis)
extraradical hyphal networks showed any preferences towards certain forms of
organic N (chitin of fungal or crustacean origin, DNA, clover biomass, or
albumin) administered in spatially discrete patches, and how the presence of AM
fungal hyphae affected other microbes. By direct 15N labeling, we also quantified
the flux of N to the plants (Andropogon gerardii) through the AM fungal hyphae
from fungal chitin and from clover biomass. The AM fungal hyphae colonized
patches supplemented with organic N sources significantly more than those
receiving only mineral nutrients, organic carbon in form of cellulose, or
nothing. Mycorrhizal plants grew 6.4-fold larger and accumulated, on average,
20.3-fold more 15N originating from the labeled organic sources than their
nonmycorrhizal counterparts. Whereas the abundance of microbes (bacteria, fungi,
or Acanthamoeba sp.) in the different patches was primarily driven by patch
quality, we noted a consistent suppression of the microbial abundances by the
presence of AM fungal hyphae. This suppression was particularly strong for
ammonia oxidizing bacteria. Our results indicate that AM fungi successfully
competed with the other microbes for free ammonium ions and suggest an important
role for the notoriously understudied soil protists to play in recycling organic
N from soil to plants via AM fungal hyphae.
PMID- 29951864
TI - "I Kept It to Myself": Young Jamaican Men Who Have Sex with Men's Experiences
with Childhood Sexual Abuse and Sexual Assault.
AB - The prevalence of HIV is exceptionally high among Jamaican men who have sex with
men (JMSM) compared to similar populations within the Caribbean. A noticeable gap
in the literature is the impact of childhood sexual abuse (CSA) and sexual
assault on the state of the epidemic among this population. This study focused on
JMSM's experiences with CSA and sexual assault and how these domains relate to
HIV prevention. We analyzed qualitative data from 20 semi-structured in-depth
interviews and focus group discussions with 10 men. Common themes emerged that
highlight the patterns and nature of the abuse, the characteristics of the
perpetrators, and the ways in which participants engage agency and resiliency as
a basis to reclaim personal power. These findings serve as a catalyst for
understanding how experiences with CSA and sexual assault affect the lives of
young JMSM; how those experiences may impact attitudes and behaviors regarding
HIV testing, engagement in care; and have implications for shaping legal policy,
clinical, and mental health services for JMSM survivors.
PMID- 29951865
TI - Electrogram characteristics of the coronary sinus in cases requiring epicardial
ablation within the coronary sinus for creating a conduction block at the left
lateral mitral isthmus.
AB - BACKGROUND: Left lateral mitral isthmus (LLMI) linear ablation is a safe and
effective technique for treating left mitral flutter. LLMI linear ablation with
pulmonary vein isolation may reduce the recurrence of persistent atrial
fibrillation. However, epicardial ablation within the coronary sinus (CS) is
often required to create the LLMI block line. If the necessity for epicardial
ablation is checked before ablation, complications may be reduced. METHODS: We
recruited 135 patients who underwent their first LLMI ablation and divided them
into two groups, one group not requiring epicardial ablation for creating a
conduction block at the LLMI (Endo group) and another requiring it (Epi group).
These two groups were compared in terms of the electrogram characteristics of the
CS. RESULTS: Bidirectional block through the LLMI was achieved in 94.8% of
patients. In 42% of these patients, not only the endocardium but also the
epicardium was ablated. As for the electrogram, the Endo group had lower atrium
voltage and atrioventricular voltage ratios (p = 0.009) than the Epi group before
LLMI ablation. By contrast, there were no significant differences in the atrium
voltage and the atrioventricular voltage ratio between these two groups after
LLMI ablation. CONCLUSIONS: For creating a conduction block at the LLMI, the
atrium voltage and the atrioventricular voltage ratio in the CS before ablation
are important. The atrioventricular voltage ratio is a crucial criterion for
determining whether epicardial ablation is necessary; furthermore, the
atrioventricular voltage ratio in the CS must be reduced with or without
epicardial ablation.
PMID- 29951866
TI - Novel steps forward in the histopathology of non-celiac gluten sensitivity,
authors' reply.
PMID- 29951867
TI - Cross-cultural validation of the German version of the Four-Dimensional Symptom
Questionnaire (4DSQ) in multimorbid elderly people.
AB - PURPOSE: Psychosomatic symptoms and mental health problems are highly prevalent
in multimorbid elderly people challenging general practitioners to differentiate
between normal stress and psychopathological conditions. The 4DSQ is a Dutch
questionnaire developed to detect anxiety, depression, somatization, and distress
in primary care. This study aims to analyze measurement equivalence between a
German version and the original Dutch instrument. METHODS: A Dutch and a German
sample of multimorbid elderly people, matched by gender and age, were analyzed.
Equivalence of scale structures was assessed by confirmatory factor analysis
(CFA). To evaluate measurement equivalence across languages, differential item
functioning (DIF) was analyzed using Mantel-Haenszel method and hybrid ordinal
logistic regression analysis. Differential test functioning (DTF) was assessed
using Rasch analysis. RESULTS: A total of 185 German and 185 Dutch participants
completed the questionnaire. The CFA confirmed one-factor models for all scales
of both 4DSQ versions. Nine items in three scales were flagged with DIF. The
anxiety scale showed to be free of DIF. DTF analysis revealed negligible scale
impact of DIF. CONCLUSIONS: The German 4DSQ demonstrated measurement equivalence
to the original Dutch instrument. Hence, it can be considered a valid
questionnaire for the screening for mental health problems in primary care.
PMID- 29951868
TI - Association of use of rehabilitation services with development of osteoporosis
among patients with rheumatoid arthritis: a nationwide population-based cohort
study.
AB - : This is the first study that has found that rehabilitation services (RS)
intervention, following the onset of rheumatoid arthritis (RA), may significantly
reduce the risk of osteoporosis in RA patients. Those patients who received more
than five sessions of RS had the greatest benefit for the prevention of
osteoporosis. INTRODUCTION: People with rheumatoid arthritis have increased risk
of developing osteoporosis (OP). It remains unclear whether use of rehabilitation
services can reduce the risk of developing OP. We conducted a longitudinal cohort
study to compare the effect of RS on the risk of OP in Taiwanese individuals with
RA. METHODS: A national health insurance database was used to identify 2693 newly
diagnosed RA patients, 20-70 years old, between 1998 and 2007. Among them, 808
received RS after the onset of RA (RS users) and 1885 patients did not receive RS
(non-RS users). All enrollees were followed until the end of 2012 to record
incident cases of OP. A Cox proportional hazards regression model was used to
compute adjusted hazard ratios (aHRs) for the relationship of use of RS with OP.
RESULTS: During the 15-year follow-up, 358 RS users and 1238 non-RS users
developed OP, corresponding to incidence rates of 87.24 and 129.27 per 1000
person-years, respectively. Use of RS was significantly associated with a lower
risk of OP (aHR 0.62; 95% confidence interval [CI] = 0.56-0.71). Those who
received more than five sessions of RS had the greatest benefit (aHR 0.47; 95% CI
= 0.38-0.56). CONCLUSIONS: The integration of RS into the clinical management of
patients with RA may decrease their risk of developing OP.
PMID- 29951869
TI - Potential antidiabetic activity and molecular docking studies of novel
synthesized 3.6-dimethyl-5-oxo-pyrido[3,4-f][1,2,4]triazepino[2,3-a]benzimidazole
and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole derivatives.
AB - Diabetes affects a large population of the globe and is considered as a leading
cause of death. Many synthetic and natural inhibitors have been developed for
diabetes treatment. Herein, we report the potential antidiabetic activity of two
new heterocyclic systems, namely 3.6-dimethyl-5-oxo
pyrido[3,4f][1,2,4]triazepino[2,3-a]benzimidazole (I) and 10-amino-2-methyl-4-oxo
pyrimido[1,2-a]benzimidazole (II) against three related enzymes: alpha-amylase,
alpha-glucosidase and beta-galactosidase. Compounds I and II were synthesized by
the action of DMF-DMA and dimethyl sulfate in the presence of water on 2-methyl
3H-benzimidazolo[1,2b][1,2,4]triazepin-4(5H)-one, and are characterized by single
X-ray diffraction. The binding interaction modes in the active sites of I and II
and targeted enzymes (stable complexes ligand-receptor) are emphasized using the
molecular docking approach by applying the Lamarckian genetic algorithm method.
Furthermore, plausible mechanisms have been proposed explaining their synthesis.
Hirshfeld surface analysis reveals the nature of molecular interactions and
fingerprint plots provide information about the percentage contribution from each
individual molecular contact to the structure surface. Graphical abstract Left
Molecular packing of 1,4-dimethyl-2-oxo-pyrimido[1,2-a]benzimidazole hydrate.
Right Docking active site of alpha-glucosidase.
PMID- 29951871
TI - Anti-Inflammatory Effects of Taraxasterol on LPS-Stimulated Human Umbilical Vein
Endothelial Cells.
AB - In the present study, we used the human umbilical vein endothelial cells (HUVECs)
to investigate the anti-inflammatory effects and mechanism of taraxasterol on
vascular inflammation. HUVECs were pre-treated with taraxasterol 1 h before
lipopolysaccharide (LPS) treatment. The concentrations of TNF-alpha, IL-8, PGE2,
and NO were measured. The expression of VCAM-1, ICAM-1, iNOS, COX-2, NF-kappaB,
and LXRalpha was detected by western blot analysis. The results showed that
taraxasterol not only reduced the production of TNF-alpha, IL-8, PGE2, and NO
induced by LPS, but also reduced the expression of iNOS and COX-2. Taraxasterol
also suppressed LPS-induced NF-kappaB activation and VCAM-1 and ICAM-1
expression. Furthermore, taraxasterol concentration-dependently increased the
expression of LXRalpha. The inhibition of taraxasterol on TNF-alpha, IL-8, PGE2,
and NO production can be reversed by geranylgeranyl diphosphate (GGPP, the
LXRalpha inhibitor). Here, we found that taraxasterol inhibited vascular
inflammation through activating LXRalpha.
PMID- 29951870
TI - Current Understanding of Epidemiology, Pathophysiology, and Management of
Atypical Femur Fractures.
AB - PURPOSE OF REVIEW: To summarize reports published since the 2013 American Society
of Bone and Mineral Research Task Force Report on atypical femoral fractures
(AFF). RECENT FINDINGS: The absolute incidence of AFFs remains low. AFFs are
primarily associated with prolonged bisphosphonate (BP) exposure, but have also
been reported in unexposed patients and those receiving denosumab for
osteoporosis and metastatic bone disease. Asians may be more susceptible to AFFs.
Lateral femoral bowing and varus hip geometry, which increase loading forces on
the lateral femoral cortex, may increase AFF risk. Altered bone material
properties associated with BP therapy may predispose to AFFs by permitting
initiation and increasing propagation of micro-cracks. Relevant genetic mutations
have been reported in patients with AFFs. Single X-ray absorptiometry femur scans
permit early detection of incomplete and/or asymptomatic AFFs. Orthopedists
recommend intramedullary rods for complete AFFs and for incomplete,
radiologically advanced AFFs associated with pain and/or marrow edema on MRI.
Teriparatide may advance AFF healing but few data support its efficacy. Greater
understanding of biological and genetic predisposition to AFF may allow
characterization of individual risk prior to initiating osteoporosis therapy and
help allay fear in those at low risk for this complication, which remains rare in
comparison to the osteoporotic fractures prevented by antiresorptive therapy.
PMID- 29951872
TI - Erythropoietin Treatment Ameliorates Lupus Nephritis of MRL/lpr Mice.
AB - An increasing body of data has shown that erythropoietin (EPO) plays multiple
roles in inflammation control and immunoregulation. However, less attention has
been given to its effects on lupus nephritis (LN). In this study, we investigated
the therapeutic effects of EPO on LN in MRL/lpr mice, a well-studied animal model
for lupus. MRL/lpr mice were randomly divided into an EPO and control group. Mice
in the EPO group were treated with EPO; saline was given to the control group.
Both groups were treated for 10 weeks. We analyzed the differences of general
disease condition, histopathologic changes, Th lymphocytes subsets, and the
expression of inflammatory factors of mice between the groups. Compared to the
control group, mice in the EPO group showed less spleen hyperplasia, less urinary
protein, and lower serum anti-dsDNA antibody; they also had lower renal
histopathologic scores and less deposition of IgG/C3 within glomeruli. Moreover,
Th1 and Th17 levels were decreased, while Th2 and Treg levels were increased in
the spleen, and the expression of inflammatory cytokines decreased in both the
spleen and kidneys. EPO increased Th2 and Treg lymphocytes, decreased Th1, Th17
lymphocytes in the spleen, and inhibited the inflammatory reactions in both the
spleen and kidneys, thus ameliorating LN of MRL/lpr mice.
PMID- 29951873
TI - The Time Course Pathological Changes After Burn Injury.
AB - In the present study, we aimed to explore the time course pathological changes
after burn injury. The time course microarray data of burn injury from the Gene
Expression Omnibus (GEO) was further analyzed through bioinformatics analysis.
The differential expression genes (DEGs) were identified in the early-stage vs.
control groups, middle-stage vs. control groups, and early-stage vs. middle-stage
groups after burn injury, followed by pathway enrichment analysis. Gene modules
associated with burn injury progression were identified through weighted gene co
expression network analysis (WGCNA), and hub genes were identified via network
topology analysis. There were a total of 745 DEGs in the early vs. control group,
1104 DEGs in mid vs. control, and 61 DEGs in early vs. mid group. The significant
pathways enriched by DEGs in the middle stage were also enriched by DEGs in the
early stage. Immunodeficiency was a significant pathway specific for the DEGs in
the early stage. There were 19 overlapped genes, such as myeloperoxidase,
transcobalamin, and interferon-induced protein with tetratricopeptide repeats 1,
among DEGs in early vs. control, middle vs. control, and early vs. middle groups.
WGCNA identified three gene modules that were significantly associated with burn
injury progression. Furthermore, we identified several gene modules and
biological processes that might be associated with burn injury progression, and
such results may be beneficial in understanding the underlying mechanisms and
developing novel drugs.
PMID- 29951874
TI - Cyclic Stretching Exacerbates Tendinitis by Enhancing NLRP3 Inflammasome Activity
via F-Actin Depolymerization.
AB - Modern molecular techniques have highlighted the presence of inflammation
throughout the spectrum of tendinopathy. Previous studies have suggested that
excessive inflammation in the tendon is a major factor leading to poor clinical
treatment. Furthermore, the NLRP3 inflammasome, as a new term, is closely
associated with the pathogenesis of many diseases. In the present study, we
examined whether the NLRP3 inflammasome contributes to the development of
tendinitis and whether cyclic stretching plays a prominent role in inflammation
in the tendon. In the present study, we showed that hydrogen peroxide (H2O2)
remarkably enhances the expression and release of IL-1beta, TNF-alpha, and IL-6.
The maturation of IL-1beta, induced by H2O2, depends on the activation of the
NLRP3 inflammasome. Cyclic stretching enhances the maturation of IL-1beta via
promoting H2O2-induced NLRP3 inflammasome activation in tenocytes. Furthermore,
we also found that the depolymerization of filamentous actin (F-actin) was
required for cyclic stretching-enhanced NLRP3 inflammasome activation. The
present study suggests that NLRP3 inflammasome plays an important regulatory role
in the pathogenesis of tendinitis. Disruption of the cytoskeleton by cyclic
stretching exerts a proinflammatory effect via further activating the NLRP3/IL
1beta pathway and hence contributes to tendinitis. These results may provide
theoretical support for a new treatment strategy for preventing excessive
inflammation in the tendon.
PMID- 29951875
TI - Clindamycin Administration Increases the Incidence of Collagen-Induced Arthritis
in Mice Through the Prolonged Impact of Gut Immunity.
AB - The profound influence of gut flora on host immune system and its link with
autoimmune disorders have been established. However, the role of certain
antibiotic in progression of autoimmune disorder is still confusing. Here, we
employed a collagen-induced arthritis (CIA) model to explore the role of
clindamycin administration in different scenarios. In the first scenario, mice
treated with antibiotics for 4 weeks were performed with the induction of CIA
immediately. The results showed that clindamycin administration promoted the
incidence and severity of CIA, while the recipients of vancomycin showed
completed tolerance. We also found that increased gut-associated Th1 and Th17
cells might be related to the subsequent expansion of collagen-specific immune
response. In the second scenario, mice treated with antibiotics for 4 weeks were
performed with CIA induction 4 weeks later. Notably, clindamycin administration
showed a prolonged impact on the incidence and severity of CIA, as well as the
gut immunity as compared to vancomycin administration. In addition, antibody
depletion of integrin alpha4beta7 systemically resulted in an impaired CIA
response, underlining the influence of gut immunity. In the mice that received
clindamycin, the abundance of anaerobic bacteria was significantly decreased and
showed little recovery at 4 weeks later. Our observations highlighted the
different characteristics of antibiotic administration on the development of
autoimmune disorders and indicated its link with gut immunity.
PMID- 29951876
TI - CD8+ Foxp3+ T Cells Affect Alveolar Bone Homeostasis via Modulating Tregs/Th17
During Induced Periodontitis: an Adoptive Transfer Experiment.
AB - Periodontitis is a dysbiotic bacteria-mediated disease characterized by
periodontal inflammations and alveolar bone damage. Its mechanisms were
complicated, involving an inflammation-mediated bone destruction. We sought to
determine roles and rules that CD8+ regulatory T cells (CD8+ Tregs) affect
alveolar bone homeostasis during periodontitis. Presence of CD8+ Tregs in the
gingiva, cervical lymph nodes (CLNs), and spleens of healthy or periodontitis
animals was analyzed. CD8+ regulatory T cells from periodontitis animals were
sorted by magnetic-activated cell sorting and fluorescent-activated cell sorting
technique, subsequently injected into recipient animals to set adoptive transfer
model. We induced experimental periodontitis on transfer models and equal number
healthy animals. Four weeks later, their alveolar bone loss and osteoclast
coverage length were measured. We also detected CD8+ Tregs, CD4+ T cell, CD4+
Tregs, Th17 cell, and IL-1beta, IL-6, IL-10, IL-17A, RANKL, TGF-beta expression
in the gingiva, CLNs, and spleen to illustrate possible working mechanism of CD8+
regulatory T cells. Periodontitis does not induce significant change on
proportion or amount of CD8+ Tregs. Adoptive transfer of CD8+ Tregs reduces
alveolar bone destruction and osteoclast formation. In addition, experimental
periodontitis increases percentage of Th17 cells and decreases CD4+ Tregs in the
gingiva and CLNs. More IL-1beta, IL-6, IL-17A, and RANKL, and less IL-10 and TGF
beta are also detected in the gingiva and CLNs from animals with periodontitis
than the one from healthy animals. Adoptive transfer of CD8+ regulatory T cells
remedies all above pathological change effectively. We did not find any
significant difference in spleen, regardless group and detected items. Outcomes
of present study clarify function that CD8+ regulatory T cells affect alveolar
bone homeostasis, and disclose its possible working mechanisms. CD8+ regulatory T
cells protect alveolar bone via reducing osteoclastogenesis and modulating local
immune response.
PMID- 29951877
TI - The Influence of LPS-Induced Maternal Inflammation on Postnatal Collagen-Induced
Arthritis.
AB - Maternal health and nutritional status influence offspring health and the
diseases that may develop in them. The effects of maternal inflammation on
offspring from the perspective of the inflammatory response and immune changes
are not fully understood. We hypothesized that maternal inflammation modulates
immune and metabolic functions, affecting the pathophysiology of inflammatory
diseases in offspring. This study investigated whether maternal inflammation
affects the onset of collagen-induced arthritis (CIA), a murine model of human
rheumatoid arthritis. Female DBA/1J mice received a single intraperitoneal
injection of lipopolysaccharide (LPS) 5 days before conception. Male offspring of
LPS-treated dams were placed in the maternal LPS group (MLG). To induce CIA, type
II collagen (CII) was emulsified with Freund's complete adjuvant and injected
twice into each mouse, at 13 and 16 weeks. The offspring were sacrificed at 26
weeks to analyze immunological and metabolic parameters. The degree of joint
swelling at an early stage of CIA was lower in the MLG than in the control group.
From histological analysis, the severity of joint destruction (severity of
arthritis score) and CII-specific IgG titer were significantly lower in the MLG.
However, at 26 weeks, serum interleukin (IL)-6 levels, an index of CIA disease
activity, were significantly higher in the MLG. Moreover, serum leptin levels
were lower in the MLG, and a negative correlation between leptin and serum IL-6
was observed. In conclusion, maternal inflammation does not merely suppress
inflammation; it may delay CIA in offspring. The analysis of inflammatory
cytokines and leptin concentrations at 26 weeks suggests that the pathophysiology
of arthritis was worsening. This study also suggests that maternal inflammation
modulates postnatal inflammatory response patterns in offspring.
PMID- 29951878
TI - Photobiomodulation reduces neutrophil migration and oxidative stress in mice with
carrageenan-induced peritonitis.
AB - The purpose of the study is to investigate the effects of two doses of
photobiomodulation (PBM) on inflammatory parameters including cell migration and
oxidative stress in carrageenan-induced peritonitis models. Twenty-eight mice
were divided into four groups: saline; untreated carrageenan (Cg; inflammation
induced); and PMB treatment groups L1 and L5 (inflammation induced with
carrageenan followed by laser irradiation at 1 and 5 J/cm2, respectively). After
30 min of inducing inflammation, laser irradiation was administered every hour,
for 4 h. Peritoneal fluid was collected for analyses. The total leukocyte number
in the peritoneal fluid in L1 (4.33 +/- 2.34) and L5 (4.95 +/- 2.86) after PBM
was lower than that in Cg (10.93 +/- 5.15 cells/ml). The average differential
count of neutrophils in the Cg was 9.46 +/- 4.31 cells/ml, which was higher than
that in L1 (3.7 +/- 2.08) and L5 (4.94 +/- 2.57). Myeloperoxidase activity was
also lower in L1 (1.89 +/- 0.43) and L5 (4.84 +/- 2.62) than in Cg (22.92 +/-
4.52 UMPO/ml). Malondialdehyde content was lower in L1 (137.5 +/- 12.33) and L5
(169.6 +/- 22.77) than in Cg (345.7 +/- 65.67 nmol/ml). Glutathione peroxidase
concentration was significantly higher in L1 (155.2 +/- 12.43) and L5 (145.9 +/-
9.585) than in Cg (79.75 +/- 9.567 MU/ml). Nitrite concentration was lower in L1
(0.3317 MUM +/- 0.0669) and L5 (0.2429 MUM +/- 0.0232) than in Cg (0.8380 MUM +/-
0.01615). Laser irradiation at 1 and 5 J/cm2 reversed the inflammation (as
indicated by neutrophil infiltration and oxidative stress).
PMID- 29951879
TI - Iron chelation inhibits cancer cell growth and modulates global histone
methylation status in colorectal cancer.
AB - Colorectal cancer (CRC) is one of the most common malignancies worldwide, and new
treatment strategies for CRC are required because of the existing chemotherapy
resistance. Iron chelators, which have been used widely for the treatment of iron
overload disease, were reported to exert anti-proliferative effects in cancer.
However, the role of iron chelation in CRC was largely unknown. In this study, we
found that the iron chelator DFO inhibited CRC cell growth significantly. In
addition, the gene expression profile was greatly changed by DFO treatment, and
many cell growth-related genes were dysregulated. Further study showed that DFO
induced a significant increase in global histone methylation in CRC cells.
However, the levels of histone methyltransferases and histone demethylases did
not change in response to DFO treatment, implying that the enzymatic activity of
these enzymes might be regulated by iron chelation. In conclusion, this study
reveals a novel role for DFO in CRC cell growth, and is the first to demonstrate
that global histone methylation is modulated by iron chelation in CRC cells.
PMID- 29951880
TI - European council of legal medicine (ECLM) guidelines for the examination of
suspected elder abuse.
AB - Article 25 of the Charter of Fundamental Rights of the European Union (adopted in
Nice on 7 December 2000) recognizes and respects the rights of older people to
lead a life of dignity and independence and to participate in social and cultural
life. It also highlights the importance of prevention and recognition of elder
abuse, especially since exposure to violence is likely as the population ages,
either in familial or in institutional settings. Elder abuse has some issues in
common with child abuse but in spite of this fact currently is less recognized.
Health professionals have a major role to play in early detection and management
of cases of elder abuse. This protocol summarizes some key concepts and
approaches to assist in the timely detection and investigation of elder abuse
cases by healthcare professionals and forensic practitioners.
PMID- 29951881
TI - MiR-1301-3p inhibits human breast cancer cell proliferation by regulating cell
cycle progression and apoptosis through directly targeting ICT1.
AB - BACKGROUND: MiRNAs regulate a variety of biological processes, such as cell
proliferation and apoptosis and play critical roles in cancer progression.
Accumulating studies have demonstrated that miR-1301-3p could regulate the
development and progression of multiple cancers, but its biological behaviors in
breast cancer (BC) are still elusive. METHODS: The expression of miR-1301-3p was
determined in BC tissues and cell lines using quantitative real-time PCR
analysis. The effects of miR-1301-3p on BC cell growth, proliferation, cell cycle
distribution, and apoptosis were also explored in vitro using MTT, colony
formation and Flow cytometry assays. The potential target gene of miR-1301-3p was
determined by dual-luciferase reporter assay and verified by quantitative real
time PCR and western blot analysis. RESULTS: We found the expression of miR-1301
3p was observably significantly down-regulated in BC tissues and cell lines. MiR
1301-3p expression in BC tissues was significantly associated with tumor size and
clinical stage. Gain-of-function assays demonstrated that miR-1301-3p inhibited
the cell growth and proliferation in breast cancer cell lines, MCF-7 and T-47D.
Moreover, up-regulation of miR-1301-3p induced cell cycle G0/G1 phase arrest and
apoptosis. Mechanistically, up-regulation of miR-1301-3p reduced the expression
of CDK4, Cyclin D1, Bcl-2, but elevated the expression of p21, Bad and Bax. ICT1
was confirmed as a direct target of miR-1301-3p. Furthermore, ICT1 overexpression
could partially reverse the effects of miR-1301-3p on BC cell proliferation, cell
cycle progression and apoptosis. CONCLUSION: Our observations suggested that miR
1301-3p inhibits cell proliferation via inducing cell cycle arrest and apoptosis
through targeting ICT1, and might be a therapeutic target for BC.
PMID- 29951882
TI - Repeat recurrence and malignant transition of phyllodes tumors of the breast.
AB - BACKGROUND: This study aimed to assess their characteristics and clinical course
of each histologic type of the behavior of phyllodes tumor (PT). METHODS: We
retrospectively reviewed 124 patients with PTs who underwent surgical treatment
from 2003 to 2011. PTs were classified as benign, borderline, and malignant using
surgical specimens. The clinicopathological characteristics according to solitary
and multiple lesions on ipsilateral breast and histological change after local
recurrence were examined. RESULTS: The median patient age was 42 years (range 12
72 years). The final pathologic diagnosis was benign PTs in 95 patients (76.6%),
borderline PTs in 21 (16.9%), and malignant PTs in 8 (6.5%). The size of benign
PTs [median 4.2 cm (range 1-21 cm)] was significantly smaller than that of
malignant PTs [median 11.3 cm (range 6-27 cm)] (p < 0.001). Eight of the 95
benign PTs (8.4%) had multiple lesions, while all malignant PTs had solitary
lesion. With a median follow-up period of 45 months, five patients with malignant
PTs (62.5%) developed distant metastases while 13 patients with benign PTs
(13.5%) and 6 patients with borderline PTs (28.6%) had local recurrence only
without malignant transition. The median overall survival period of those with
malignant PTs was 22.5 months (range 5-109 months). CONCLUSIONS: Histologically
benign and borderline PTs had a good prognosis without malignant transition even
after developing repeat recurrence in contrast with malignant PTs that might be a
solitary lesion.
PMID- 29951884
TI - Regioselective four-component synthesis of new tetrazolo[1,5-a]quinoline-based 2
amino-1,4-dihydropyridine and pyridin-2(1H)-one derivatives using nano-ZnO
catalysis.
AB - Four-component reaction between primary amines, dialkylacetylendicarboxylates,
tetrazolo[1,5-a] quinoline-4-carbaldehyde and ethyl-2-cyanoacetate in the
presence of 1,4-diaza-bicyclo[2.2.2]octane and zinc oxide nanoparticles results
to the regioselective production of new tetrazolo[1,5-a]quinoline-based 2-amino
1,4-dihydropyridine or pyridin-2(1H)-one derivatives in good to high yields. The
selectivity of the catalyzed reaction toward the generation of the
dihydropyridine or pyridin-2(1H)-one derivatives was found to be strongly
dependent on the size of the alkyl groups in the ester moieties of the acetylenic
esters. According to single-crystal X-ray diffraction and NMR studies, the
pyridin-2(1H)-one derivatives involve a restricted rotation around the C-C bond
connecting the tetrazoloquinoline and dihydropyridinone cyclic systems.
PMID- 29951883
TI - Pharmacologic Management of Cancer Therapeutics-Induced Cardiomyopathy in Adult
Cancer Survivors.
AB - PURPOSE OF REVIEW: The number of cancer survivors is exponentially increasing
worldwide, due to both advances in cancer detection and treatment strategies, as
well as the aging and growth of the population. This decrease in cancer mortality
has brought forth a concurrent increase of non-ischemic (toxic) dilated
cardiomyopathy in the survivor population, also known as cancer therapeutics
induced cardiomyopathy (CTIC). The optimal pharmacological management for this
condition is still elusive, and hence, the focus of this work. RECENT FINDINGS:
Our review of the literature did not identify any prospective randomized clinical
trial of CTIC in adult cancer survivors, neither published nor in progress.
However, available data seem to suggest that, when managed with standard
guideline-derived medical therapy, the outcomes of CTIC are comparable to that of
idiopathic dilated cardiomyopathy (IDC). Nonetheless, the evidence behind this
strategy is inadequate. Until new information becomes available, pharmacological
management of CTIC must parallel that of IDC. However, implementation of such may
be hindered by other cancer therapeutics-induced comorbidities and conditioned by
the particular effects of heart failure pharmacotherapy on cancer outcomes. This
work succinctly reviews these three areas, in the context of adult cancer
survivors.
PMID- 29951885
TI - Synthesis of some new triamide derivatives via Ugi five-component reaction in
aqueous solution.
AB - Triamide derivatives have been synthesized in good yields in a novel, one-pot,
five-component, and efficient process by the reaction of Z-oxazolone, water,
primary amines, aldehydes, isocyanides, in the presence of catalytic amount of
KAl(SO4)2.12H2O (alum) as a non-toxic, reusable, inexpensive, and easily
available reagent via Ugi reaction in aqueous solution.
PMID- 29951886
TI - Metoprolol has a similar therapeutic effect as amlodipine on BP lowering in
hypertensive patients with obstructive sleep apnea.
AB - PURPOSE: beta-Blocker use has been controversial for a long time in the
management of hypertensive patients with obstructive sleep apnea (OSA). The aim
of present study was to compare the effects of metoprolol on BP lowering with
amlodipine in hypertensive OSA patients. METHODS: Hypertensive subjects with OSA
were randomly assigned to metoprolol and amlodipine groups, receiving 12 weeks of
oral either metoprolol (47.5 mg once daily) or amlodipine (5 mg once daily)
treatment. At baseline and after the 12-week treatment period, 24-h ambulatory
blood pressure monitoring was performed in both groups. RESULTS: Both of
metoprolol and amlodipine treatments significantly lowered 24-h blood pressure
(BP) (from 143/88 to 132.3/81.6 mmHg; from 141.3/84.5 to 133.7/80.8 mmHg),
daytime BP (from 146/90.2 to 136.4/84.6 mmHg; from 145.1/87.6 to 138.2/84.1
mmHg), and nighttime BP (from 139.1/83.9 to 125.7/76.2 mmHg; from 134.5/78.5 to
125.8/74.1 mmHg) (all P < 0.05). But there were no significant differences
between the groups in BP variability (P > 0.05). Besides, metoprolol
significantly reduced daytime heart rate (HR) (P < 0.05), while 24-h and
nighttime HR values had no remarkable changes compared with baseline (P > 0.05).
CONCLUSIONS: Metoprolol had similar therapeutic effects on BP lowering as
amlodipine and could not decrease HR during the nighttime in hypertensive
patients with OSA.
PMID- 29951887
TI - First Infusion Reactions are Mediated by FcgammaRIIIb and Neutrophils.
AB - PURPOSE: Administration of therapeutic monoclonal antibodies (mAbs) is frequently
accompanied by severe first infusion reactions (FIR). The mechanism driving FIR
is still unclear. This study aimed to investigate the cellular and molecular
mechanisms causing FIR in humanized mouse models and their potential for
evaluating FIR risk in patients. METHODS: Mice humanized for Fc gamma receptors
(FcgammaRs) were generated by recombination-mediated genomic replacement. Body
temperature, cytokine release and reactive oxygen species (ROS) were measured to
assess FIR to mAbs. RESULTS: Infusion of human mAb specific for mouse transferrin
receptor (HamTfR) into FcgammaR-humanized mice, produced marked transient
hypothermia accompanied by an increase in inflammatory cytokines KC and MIP-2,
and ROS. FIR were dependent on administration route and Fc-triggered effector
functions mediated by neutrophils. Human neutrophils also induced FIR in wild
type mice infused with HamTfR. Specific knock-in mice demonstrated that human
FcgammaRIIIb on neutrophils was both necessary and sufficient to cause FIR.
FcgammaRIIIb-mediated FIR was abolished by depleting neutrophils or blocking
FcgammaRIIIb with CD11b antibodies. CONCLUSIONS: Human FcgammaRIIIb and
neutrophils are primarily responsible for triggering FIR. Clinical strategies to
prevent FIR in patients should focus on this pathway and may include transient
depletion of neutrophils or blocking FcgammaRIIIb with specific mAbs.
PMID- 29951890
TI - A Mathematical Model of the Inflammatory Response to Pathogen Challenge.
AB - The human body's immune response to bacterial challenge, even when successful in
controlling the infection, can result in negative consequences for the host,
including reduced functionality of associated tissues. We present and analyze a
low-dimensional mathematical model of this immune response to pathogen invasion,
incorporating the coordinated actions of active immune cells, and both pro- and
anti-inflammatory cytokines. The model simulates both the positive (pathogen
reduction) and negative (local tissue dysfunction) effects of the immune response
and includes the important role of immunologic memory in the process of a return
to stasis. This differential equation-based model is sufficiently general to be
applicable to a wide range of human tissues and organs.
PMID- 29951888
TI - Updates in the Pathology of Precursor Lymphoid Neoplasms in the Revised Fourth
Edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid
Tissues.
AB - PURPOSE OF REVIEW: Acute lymphoblastic leukemias (ALL) are malignant disorders of
immature B or T cells that occur characteristically in children, usually under
the age of 6 (75%). Approximately 6000 new cases of ALL are diagnosed each year
in the USA, 80-85% of which represent B-ALL forms. Most presentations of B-ALL
are leukemic, whereas T-ALL presents with a mediastinal mass, with or without
leukemic involvement. The revised fourth edition of the World Health Organization
(WHO) classification (2017) has introduced some changes in both B and T-ALL.
Here, we summarize the categories of lymphoblastic leukemia/lymphomas as defined
by the WHO and recent developments in the understanding of this group of
hematologic malignancy. RECENT FINDINGS: Two provisional categories of B-ALL have
now been identified including B-ALL, BCR-ABL1-like, and B-ALL with iAMP21. The
Philadelphia chromosome-like B-ALL includes forms of the disease that shares the
expression profiling of B-ALL with t(9;22) but lack such rearrangement. The
second one shows amplification of part of the chromosome 21. Both entities are
associated with worse prognosis. Within the T-ALL group, an early precursor T
cell form has now been introduced as a provisional category. Such group
demonstrates expression of stem cell and myeloid markers in conjunction with the
T cell antigens. The current review summarizes the recent updates to the WHO
classification.
PMID- 29951889
TI - Molecular Insights Into Pathogenesis of Peripheral T Cell Lymphoma: a Review.
AB - PURPOSE OF REVIEW: Peripheral T cell lymphoma (PTCL) is a heterogeneous group of
lymphoproliferative neoplasms, with at least 29 distinct entities described in
current WHO classification. Using present diagnostic approaches, more than a
third of PTCL cases cannot be classified, hence designated as PTCL-not otherwise
specified (PTCL-NOS). Herein, we summarize the current genomic findings and their
role in the molecular pathogenesis in different PTCL entities. RECENT FINDINGS:
Gene expression profiling (GEP) studies have identified distinct molecular
signatures for accurate diagnosis and elucidated oncogenic pathways enriched in
major PTCL entities. Furthermore, genomic characterization has identified
recurrent somatic mutations and potential therapeutic targets. Further efforts
are underway to develop genetically faithful murine models. GEP studies have
identified molecular subgroups of PTCL, characterized by distinct genetic and
epigenetic alterations. Understanding the molecular mechanisms of T cell
lymphomagenesis using in vivo model will help to reveal novel therapeutic
targets.
PMID- 29951892
TI - The microRNA signatures: aberrantly expressed miRNAs in prostate cancer.
AB - MicroRNAs (miRNAs) are short, non-coding, conserved, oligonucleotides that are
regulatory in nature and are often dysregulated in many cancers including
prostate cancer. Depending on the level of complementarity between the miRNA and
mRNA target, they can either inhibit translation or degrade the target mRNA.
MiRNAs expression is specific to the type of cancer, its stage and level of
metastasis, making miRNAs potential stage-specific biomarkers of cancer. Recent
research has shown that these miRNAs have the potential to be a diagnostic and
prognostic non-invasive biomarker for various cancers including prostate cancer.
Various miRNAs have been reported as novel biomarkers for prostate cancer
therapy. However, there is inconsistency in the data reported and no overlapping
expression pattern could be found. In this review, we have highlighted the most
consistently reported dysregulated miRNAs in prostate cancer from the existing
literature and discussed the currently available data on their role in regulating
the hallmarks of prostate cancer. These four most consistently reported
dysregulated miRNAs viz. miRNA-141, miRNA-375, miRNA-221 and miRNA-21 need to be
further validated in terms of their regulatory potential in regulating various
pathways important for prostate cancer management.
PMID- 29951891
TI - Molecular characterization of microtubule-associated protein 1-light chain 3B in
Megalobrama amblycephala fed with high fat/berberine diets.
AB - This study tested the effect of berberine on autophagy-related protein of
Megalobrama amblycephala fed with high fat diet under different feeding modes.
The full-length complementary DNA (cDNA) of microtubule-associated protein 1
light chain 3B (LC3B) was 1871 bp with an open reading frame of 378 bp encoding
125 amino acids. High homology at nucleotide and amino acid sequences to carp
LC3B was revealed though sequence analysis. LC3B was mainly (P < 0.05) expressed
in hepatopancreas but lower in several peripheral tissues, including gill,
intestine, kidney, and spleen. The fish (average initial weight 4.70 +/- 0.02 g)
were fed with eight experiment diets containing two lipid levels (5 and 10%) or
four berberine-feeding modes (without berberine, supplementing 50 mg/kg berberine
at 2-week intervals, 4-week intervals, or continuous) for 8 weeks. The results
showed that the numbers of autophagosomes and hepatopancreas LC3B messenger RNA
(mRNA) expression levels were significantly (P < 0.05) affected both by dietary
lipid level and beberine feeding mode, and the highest (P < 0.05) numbers of
autophagosomes and LC3B expression levels were observed in fish at berberine
continuous feeding mode groups. The findings may provide the molecular mechanisms
underlying lipid metabolism and immune effect of berberine, which was associated
with enhanced autophagy in fish.
PMID- 29951893
TI - Case presentation commentary on "ammonia for positron emission tomography (PET):
A promising technique for patients with LBBB and suspicion of coronary artery
disease".
PMID- 29951894
TI - Better characterization of dipyridamole-induced myocardial stunning by systolic
wall thickening. A gated perfusion SPECT study.
AB - AIM AND PATIENTS: The aim of the present study was to assess the additional value
of systolic wall thickening to myocardial perfusion in diagnosing myocardial
stunning induced by dipyridamole infusion. We selected 52 ischemic patients (43
males; mean age 65.5 +/- 7.64), with CAD documented by angiography. Ischemia was
defined as a summed difference score >= 5. All patients underwent a 2-day gated
perfusion SPECT protocol. The patients received a dose of 740 MBq of 99mTc
tetrofosmin after stress and at rest. RESULTS: The post-stress LVEF was
significantly lower than rest LVEF (48.3% +/- 14.5% vs. 50.7% +/- 15%; P =
0.0001). The wall thickening summed difference score was 3.97 +/- 3.84 (P =
0.0001). At a multivariate regression analysis, only WT-SDS as independent
variable was significantly correlated with myocardial ischemia (SDS) (P = 0.001).
We divided patients according to SDS in those with mild (SDS < 8) and severe (SDS
>= 8) ischemia. WT-SDS, but not ?LVEF, was significantly different between
groups. CONCLUSIONS: WT-SDS showed a better correlation with the degree of
ischemia than the depression in the global function of the left ventricle. It
allowed to better identify the stunning phenomenon in patients submitted to
pharmacological stress.
PMID- 29951895
TI - The Role of Economic Stress and Coping Resources in Predicting Hwabyung Symptoms.
AB - This article reports the findings from a study that examined the role of economic
stress and coping resources in predicting hwabyung symptoms among Koreans in the
United States. The literal meaning of hwabyung is "fire illness" or "anger
illness." Koreans believe that chronic stress can cause the onset of hwabyung,
manifested mainly through somatic symptoms. Data collected from an anonymous
survey of 242 voluntary participants were analyzed using hierarchical multiple
regression (R2). The findings demonstrated the important role that social support
and sense of self-esteem play in explaining hwabyung symptoms. Also, the graduate
education attained in the United States appears to play positive role in reducing
the hwabyung symptoms, while being a woman can increase their vulnerability to
this indigenous psychiatric illness to Korean people. Based on the findings, the
implications for practice and suggestions for future study are discussed.
PMID- 29951897
TI - Correction to: Bayesian active probabilistic classification for psychometric
field estimation.
AB - The original version of this article neglected to mention a conflict of interest.
DLB has a patent pending on technology described in this manuscript.
PMID- 29951898
TI - Contrast-enhanced CT combined with 18-FDG PET in patients selected for
cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC):
methodological issues on diagnostic value and reliability.
PMID- 29951896
TI - Cytotoxicity of alpha-Pyrrolidinophenones: an Impact of alpha-Aliphatic Side
chain Length and Changes in the Plasma Membrane Fluidity.
AB - Pyrovalerone derivatives (alpha-pyrrolidinophenones) form a branch of synthetic
cathinones, a second most prominent group of novel psychoactive substances.
Although the toxicity of 3,4-MDPV, a progenitor of the alpha-pyrrolidinophenones,
is well described, little is known of the potential cytotoxicity of the new
members of this group entering the recreational drug market each year. The
present study assesses the cytotoxicity of members of the alpha
pyrrolidinophenone group, i.e., alpha-PVP, its longer side-chain derivatives PV8
and PV9, and their 4-fluoro- and 4-methoxy-analogs, against model cell lines for
the nervous system (SH-SY5Y), liver (Hep G2) and upper airway epithelium (RPMI
2650), and cardiomyocytes (H9C2(2-1)). Additionally, an impact of pyrovalerones
on the fluidity of the plasma membrane, as the potential mechanism of their
cytotoxicity, was examined. The longer side-chain alpha-pyrrolidinophenones and
their fluoro- and methoxy-analogs produce more pronounced maximal cytotoxicity,
with regard to mitochondrial activity and cell membrane integrity, than the five
carbon alpha-PVP and its substituted derivatives. The report demonstrates, for
the first time, that changes of fluidity of the interior part of plasma membrane
contribute to the cytotoxicity of pyrovalerone derivatives, in addition to the
previously reported mechanisms. Taking into consideration our previous findings
that PV8 and PV9 produce weaker psychostimulatory effects than alpha-PVP, the
higher cytotoxicity of the new generation of pyrovalerones can pose a serious
threat to abusers, as it is possible that longer-chain compounds may be taken in
higher doses to obtain similar levels of stimulation.
PMID- 29951899
TI - Intravoxel incoherent motion diffusion-weighted MR imaging of solid pancreatic
masses: reliability and usefulness for characterization.
AB - PURPOSE: IVIM-DW imaging has shown potential usefulness in the study of
pancreatic lesions. Controversial results are available regarding the reliability
of the measurements of IVIM-derived parameters. The aim of this study was to
evaluate the reliability and the diagnostic potential of IVIM-derived parameters
in differentiation among focal solid pancreatic lesions and normal pancreas (NP).
METHODS: Fifty-seven patients (34 carcinomas-PDACs, 18 neuroendocrine neoplasms
panNENs, and 5 autoimmune pancreatitis-AIP) and 50 subjects with NP underwent 1.5
T MR imaging including IVIM-DWI. Images were analyzed by two independent readers.
Apparent diffusion coefficient (ADC), slow component of diffusion (D), incoherent
microcirculation (Dp), and perfusion fraction (f) were calculated. Interobserver
reliability was assessed with intraclass correlation coefficient (ICC). A Kruskal
Wallis H test with Steel-Dwass post hoc test was used for comparison. The
diagnostic performance of each parameter was evaluated through receiver operating
characteristic (ROC) curve analysis. RESULTS: Overall interobserver agreement was
excellent (ICC = 0.860, 0.937, 0.968, and 0.983 for ADC, D, Dp, and f). D, Dp,
and f significantly differed among PDACs and panNENs (p = 0.002, < 0.001, and <
0.001), albeit without significant difference at the pairwise comparison of ROC
curves (p = 0.08-0.74). Perfusion fraction was higher in AIP compared with PDACs
(p = 0.024; AUC = 0.735). Dp and f were higher in panNENs compared with AIP (p =
0.029 and 0.023), without differences at ROC analysis (p = 0.07). CONCLUSIONS:
IVIM-derived parameters have excellent reliability and could help in
differentiation among solid pancreatic lesions and NP.
PMID- 29951900
TI - Reader agreement and accuracy of ultrasound features for hepatic steatosis.
AB - PURPOSE: The purpose of the study is to assess the reader agreement and accuracy
of eight ultrasound imaging features for classifying hepatic steatosis in adults
with known or suspected hepatic steatosis. METHODS: This was an IRB-approved,
HIPAA-compliant prospective study of adult patients with known or suspected
hepatic steatosis. All patients signed written informed consent. Ultrasound
images (Siemens S3000, 6C1HD, and 4C1 transducers) were acquired by experienced
sonographers following a standard protocol. Eight readers independently graded
eight features and their overall impression of hepatic steatosis on ordinal
scales using an electronic case report form. Duplicated images from the 6C1HD
transducer were read twice to assess intra-reader agreement. Intra-reader, inter
transducer, and inter-reader agreement were assessed using intraclass correlation
coefficients (ICC). Features with the highest intra-reader agreement were
selected as predictors for dichotomized histological steatosis using
Classification and Regression Tree (CART) analysis, and the accuracy of the
decision rule was compared to the accuracy of the radiologists' overall
impression. RESULTS: 45 patients (18 males, 27 females; mean age 56 +/- 12 years)
scanned from September 2015 to July 2016 were included. Mean intra-reader ICCs
ranged from 0.430 to 0.777, inter-transducer ICCs ranged from 0.228 to 0.640, and
inter-reader ICCs ranged from 0.014 to 0.561. The CART decision rule selected
only large hepatic vein blurring and achieved similar accuracy to the overall
impression (74% to 75% and 68% to 72%, respectively). CONCLUSIONS: Large hepatic
vein blurring, liver-kidney contrast, and overall impression provided the highest
reader agreement. Large hepatic vein blurring may provide the highest
classification accuracy for dichotomized grading of hepatic steatosis.
PMID- 29951901
TI - Further Classification for Node-Positive Gastric Neuroendocrine Neoplasms.
AB - BACKGROUND: For gastric neuroendocrine neoplasms (GNEN), the current AJCC lymph
node (N) stage classifies patients into N0/N1 disease (with/without locoregional
nodal metastases); however, this does not account for the number of involved
nodes. The objective of this study was to evaluate the prognostic significance of
the number of involved locoregional nodes among resected GNEN. METHODS: The
National Cancer Database (2004-2014) was queried for GNEN patients who had
undergone partial/total gastrectomy with known nodal status. Nearest-neighborhood
grouping was used to identify survival clusters by number of metastatic nodes and
to use these groupings to construct a new N classification (pN). External
validation was performed using the SEER database. Kaplan-Meier analysis and Cox
regression models were used to assess the prognostic strength of the pN
classification. RESULTS: One thousand two hundred seventy-five patients met study
inclusion criteria. Patients with 1-6 positive nodes (pN1) demonstrated a
distinct survival pattern from patients with > 6 positive nodes (pN2) as well as
those with no positive nodes (N0) {5-year OS N0: 80% (95% CI 77-83%) vs. 65% (95%
CI 61-69%) vs. 43% (95% CI 33-53%), p < 0.001}. On external validation, the pN
classification demonstrated strong discriminatory ability for survival {5-year OS
N0: 70% (95% CI 65-75%) vs. pN1:53% (95% CI 46-59%) vs. pN2:18% (95% CI 9-29%), p
< 0.001}. On multivariable analysis, the pN classification remained an
independent predictor of OS. CONCLUSIONS: The number of metastatic lymph nodes is
an independent prognostic factor in GNEN. Current AJCC N1 disease contains two
groups of patients with distinctive prognoses, hence needs to be subclassified
into pN1 (1-6 positive lymph nodes) and pN2 (> 6 positive nodes).
PMID- 29951902
TI - Effect of Health Education on Female Teachers' Knowledge and Practices Regarding
Early Breast Cancer Detection and Screening in the Jazan Area: a Quasi
Experimental Study.
AB - : Educational programs are important tools for breast cancer prevention. The
purpose of this study was to assess the effectiveness of health education in
improving the knowledge and practices of female teachers regarding screening
tools and the early detection of breast cancer. A two-group quasi-experimental
design was conducted among 150 female teachers, who were selected from 75 schools
of the Jazan General Administration of Education. Schools were chosen by a simple
cluster randomization method and non-randomly assigned to either the intervention
or control group. Eligible participants were recruited by a simple randomization
method, proportional to the total number of teachers at each school. Those in the
intervention group (n = 75) were compared to the control group (n = 75) at
baseline, as well as at 6 weeks and 3 months post-intervention. Knowledge of
breast cancer screening tools was measured using a modified version of the Breast
Cancer Knowledge test. Breast self-examination, clinical breast examination, and
mammography practices were also measured. Compared to the control group, the
intervention group showed a statistically significant increase in knowledge and
practice levels at both 6 weeks and 3 months post-intervention. Thus, the results
of this study provide evidence that group health education programs are effective
in improving breast cancer knowledge and practices in female teachers. CLINICAL
TRIAL REGISTRATION NUMBER: NCT03398057 .
PMID- 29951903
TI - Perceptions of Cancer Status Disclosure in Lebanon.
AB - In Lebanon, cancer used to be regarded as a taboo and referred to as "the
disease" and was rarely disclosed to patients. However, patients are now
increasingly interested in knowing their cancer status but with varying degrees
of information requested. The aim of this qualitative descriptive study was to
explore the perceptions of cancer patients, their families, oncologists, and
healthy individuals concerning the disclosure of cancer prognosis. In-depth
interviews were conducted with 21 family members, 20 middle-aged cancer patients,
11 elderly cancer patients, 22 healthy individuals, and 6 oncologists at the
American University of Beirut Medical Center. The interviews focused on the
following: general perception of cancer in Lebanese society, type, and extent of
information that should be disclosed, factors affecting patient autonomy, and
elements contributing to the decisions taken by oncologists and patients. The
oncologist's compassion and communication with patients affected their emotional
status greatly, and some gaps in communication skills of oncologists were in need
of standardized training courses to improve the process of cancer status
disclosure. Also, patients had an increased preference towards the disclosure of
cancer prognosis, and a desire to know the truth and this need increased as the
patient progressed to a terminal state. Future work should be directed at
addressing the needs of cancer patients through every disease stage. More
research and further deliberation are needed to confirm the findings of this
study since the Lebanese Code of Medical Practice does not protect the right of
full disclosure.
PMID- 29951904
TI - Training children aged 5-10 years in compliance control: tracing smaller figures
yields better learning not specific to the scale of drawn figures.
AB - Previously we developed a method that supports active movement generation to
allow practice with improvement of good compliance control in tracing and
drawing. We showed that the method allowed children with motor impairments to
improve at a 3D tracing task to become as proficient as typically developing
children and that the training improved 2D figure copying. In this study, we
expanded the training protocol to include a wider variety of ages (5-10-year
olds) and we made the figures traced in training the same as in figure copying,
but varied the scale of training and copying figures to assess the generality of
learning. Forty-eight children were assigned to groups trained using large or
small figures. All were tested before training with a tracing task and a copying
task. Then, the children trained over five sessions in the tracing task with
either small or large figures. Finally, the tracing and copying tasks were tested
again following training. A mean speed measure was used to control for path
length variations in the timed task. Performance on both tasks at both baseline
and posttest varied as a function of the size of the figure and age. In addition,
tracing performance also varied with the level of support. In particular, speeds
were higher with more support, larger figures and older children. After training,
performance improved. Speeds increased. In tracing, performance improved more for
large figures traced by children who trained on large figures. In copying,
however, performance only improved significantly for children who had trained on
small figures and it improved equally for large and small figures. In conclusion,
training by tracing smaller figures yielded better learning that was not,
however, specific to the scale of drawn figures. Small figures exhibit greater
mean curvature. We infer that it yielded better general improvement.
PMID- 29951905
TI - Innate lymphoid cells: key players in tissue-specific immunity.
PMID- 29951907
TI - Spiking networks as efficient distributed controllers.
AB - In the brain, networks of neurons produce activity that is decoded into
perceptions and actions. How the dynamics of neural networks support this
decoding is a major scientific question. That is, while we understand the basic
mechanisms by which neurons produce activity in the form of spikes, whether these
dynamics reflect an overlying functional objective is not understood. In this
paper, we examine neuronal dynamics from a first-principles control-theoretic
viewpoint. Specifically, we postulate an objective wherein neuronal spiking
activity is decoded into a control signal that subsequently drives a linear
system. Then, using a recently proposed principle from theoretical neuroscience,
we optimize the production of spikes so that the linear system in question
achieves reference tracking. It turns out that such optimization leads to a
recurrent network architecture wherein each neuron possess integrative dynamics.
The network amounts to an efficient, distributed event-based controller where
each neuron (node) produces a spike if doing so improves tracking performance.
Moreover, the dynamics provide inherent robustness properties, so that if some
neurons fail, others will compensate by increasing their activity so that the
tracking objective is met.
PMID- 29951908
TI - A single retinal circuit model for multiple computations.
AB - Vision is dependent on extracting intricate features of the visual information
from the outside world, and complex visual computations begin to take place as
soon as at the retinal level. In multiple studies on salamander retinas, the
responses of a subtype of retinal ganglion cells, i.e., fast/biphasic-OFF
ganglion cells, have been shown to be able to realize multiple functions, such as
the segregation of a moving object from its background, motion anticipation, and
rapid encoding of the spatial features of a new visual scene. For each of these
visual functions, modeling approaches using extended linear-nonlinear cascade
models suggest specific preceding retinal circuitries merging onto fast/biphasic
OFF ganglion cells. However, whether multiple visual functions can be
accommodated together in a certain retinal circuitry and how specific mechanisms
for each visual function interact with each other have not been investigated.
Here, we propose a physiologically consistent, detailed computational model of
the retinal circuit based on the spatiotemporal dynamics and connections of each
class of retinal neurons to implement object motion sensitivity, motion
anticipation, and rapid coding in the same circuit. Simulations suggest that
multiple computations can be accommodated together, thereby implying that the
fast/biphasic-OFF ganglion cell has potential to output a train of spikes
carrying multiple pieces of information on distinct features of the visual
stimuli.
PMID- 29951909
TI - What are the concerns and goals of women attending a urogynaecology clinic?
Content analysis of free-text data from an electronic pelvic floor assessment
questionnaire (ePAQ-PF).
AB - INTRODUCTION AND HYPOTHESIS: Understanding patients' concerns and goals is
essential for providing individualised care in urogynaecology. The study
objectives were to undertake a content analysis of free-text concerns and goals
recorded by patients using an electronic pelvic-floor questionnaire (ePAQ-PF) and
measure how these related to self-reported symptom and health-related quality-of
life (HRQOL) data also recorded using ePAQ-PF. METHODS: A total of 1996
consenting patients completed ePAQ-PF. Content analysis was undertaken of free
text responses to the item: 'Considering the issues that currently concern you
the most, what do you hope to achieve from any help, advice or treatment?' Key
content themes were identified by the lead researcher, and three researchers read
and coded all recorded responses. Student's t test was used to compare ePAQ-PF
domain scores for patients reporting concerns in the relevant domain with those
who did not. RESULTS: In total, 63% of participants who completed the
questionnaire, recorded at least one free-text item. Content analysis identified
1560 individual concerns coding into the 19 ePAQ-PF domains. Symptom scores were
significantly higher for patients reporting free-text concerns in 18 domains (p <
0.05). Additional concerns relating specifically to body image were recorded by
11% of patients. Key areas of importance emerging for personal goals included
cure/improvement, better understanding, incontinence pad use, sexual function and
surgery. CONCLUSIONS: Free-text reporting in ePAQ-PF is utilised by patients and
facilitates self-expression and discussion of issues impacting on HRQOL. The
significant relationship between recorded free-text concerns and ePAQ-PF domain
scores suggests convergent validity for the instrument. Development and
psychometric testing of a domain to assess body image is proposed.
PMID- 29951906
TI - AHR signaling in the development and function of intestinal immune cells and
beyond.
AB - The intestinal immune system is challenged daily with the task of recognizing and
eliminating pathogens while simultaneously tolerating dietary and commensal
antigens. All components must effectively coordinate to differentiate a continual
barrage of environmental cues and mount appropriate responses dependent on the
nature of the stimuli encountered. Playing a pivotal role, the aryl hydrocarbon
receptor (AHR) is a chemical sensor that detects both dietary and microbial cues
and is important for development, maintenance, and function of several types of
intestinal immune cells, particularly innate lymphoid cells (ILCs) and T cells.
In this review, we will highlight recent advances in our knowledge of the role of
AHR signaling in ILCs, T cells, B cells, and dendritic cells.
PMID- 29951910
TI - In defense of J Marion Sims.
PMID- 29951911
TI - Accuracy of postvoid residual volumes after vaginal delivery: a prospective
equivalence study to compare an automatic scanning device with transurethral
catheterization.
AB - INTRODUCTION AND HYPOTHESIS: Abnormal postvoid residual volumes (PVRV) after
delivery are common in daily clinical practice. By using an automatic scanning
device, unnecessary catheterizations can be prevented. The aim of this study was
to determine the accuracy of PVRV after vaginal delivery measured by an automatic
scanning device through a comparison with transurethral catheterization.
MATERIALS AND METHODS: This prospective observational equivalence study was
performed in patients who delivered vaginally between June 2012 and May 2017 in
three teaching hospitals in The Netherlands. After the first spontaneous void
after delivery, postvoid residual volume (PVRV) was measured with a portable
automatic scanning device (BladderScan(r) BVI 9400). Directly afterward, it was
measured by catheterization. Correlation between measurements was calculated
using Spearman's correlation coefficient and agreement plot. The primary outcome
was to validate the correlation between the BladderScan(r) compared with the gold
standard of transurethral catheterization. RESULTS: Data of 407 patients was used
for final analysis. Median PVRV as measured by BladderScan(r) was 380 ml (+/- 261
0-999 ml) and by catheterization was 375 ml (+/- 315-1800 ml). Mean difference
between measurements was -12.9 ml (+/- 178 ml). There was a very good correlation
between methods (Spearman's rho = 0.82, p < 0.001). Using a cut-ff value of >500
ml, specificity and sensitivity were 85.4 and 85.6%, respectively. CONCLUSIONS:
The BladderScan(r) (BVI 9400) measures PVRV precisely and reliably after vaginal
delivery and should be preferred over catheterization.
PMID- 29951913
TI - Acute myeloid leukemia with t(19;21)(q13;q22) and marked eosinophilia.
PMID- 29951912
TI - Prolonged treatment with arsenic trioxide (ATO) and all-trans-retinoic acid
(ATRA) for relapsed acute promyelocytic leukemia previously treated with ATRA and
chemotherapy.
AB - Prolonged therapy with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO)
is highly effective in newly diagnosed acute promyelocytic leukemia (APL) but
there is limited data on the efficacy of this regimen in the relapse setting. We
report here on 22 APL patients treated with prolonged ATRA-ATO therapy at the
time of disease relapse. Twenty patients obtained molecular complete remission
(CRm) after 2 cycles (90%). Of these, two patients underwent hematopoietic stem
cell transplant (HSCT) while the remaining proceeded to receive additional cycles
(up to a total of 5) of ATRA-ATO. With a median follow-up of 58 months from the
time of relapse (range: 21-128 months), the 4-year OS probability was 0.85 (95%
CI 0.61-0.94), DFS was 0.74 (95% CI 0.49-0.88), and EFS 0.68 (95% CI 0.45-0.83).
Two patients were resistant to ATRA-ATO salvage and five relapsed at a median of
19 months. Of these, four died due to progressive disease while three relapsed
achieved a new CRm after further salvage therapy. This experience confirms the
potentially curative effect of prolonged ATRA-ATO therapy in relapsed APL,
especially in patients with long first complete remission.
PMID- 29951914
TI - The co-occurrence of driver mutations in chronic myeloproliferative neoplasms.
AB - Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by
proliferation of one or more elements of the myeloid lineage. Key genetic
aberrations include the BCR-ABL1 gene rearrangement in Philadelphia chromosome
positive chronic myelogenous leukemia (CML) and JAK2/MPL/CALR aberrations in
Philadelphia chromosome-negative MPNs. While thought to be mutually exclusive,
occasional isolated reports of coexistence of BCR-ABL1 and JAK2, and JAK2 with
MPL or CALR aberrations have been described. Given the paucity of data, clinical
characteristics and outcome of patients harboring concurrent Philadelphia
positive and Philadelphia-negative mutations or dual Philadelphia-negative driver
mutations have not been systematically evaluated, and their clinical relevance is
largely unknown. It is difficult to determine the true relevance of co-existing
driver mutations on outcomes given the rarity of its occurrence. In this case
series, we describe those patients who had dual driver mutations detected at any
point during the course of their disease and characterized their clinical and
laboratory features, bone marrow pathology, and overall disease course.
PMID- 29951916
TI - Increased cortical involvement and synchronization during CAP A1 slow waves.
AB - Slow waves recorded with EEG in NREM sleep are indicative of the strength and
spatial extent of synchronized firing in neuronal assemblies of the cerebral
cortex. Slow waves often appear in the A1 part of the cyclic alternating patterns
(CAP), which correlate with a number of behavioral and biological parameters, but
their physiological significance is not adequately known. We automatically
detected slow waves from the scalp recordings of 37 healthy patients, visually
identified CAP A1 events and compared slow waves during CAP A1 with those during
NCAP. For each slow wave, we computed the amplitude, slopes, frequency,
synchronization (synchronization likelihood) between specific cortical areas, as
well as the location of origin and scalp propagation of individual waves. CAP A1
slow waves were characterized by greater spatial extent and amplitude, steeper
slopes and greater cortical synchronization, but a similar prominence in frontal
areas and similar propagation patterns to other areas on the scalp. Our results
indicate that CAP A1 represents a period of highly synchronous neuronal firing
over large areas of the cortical mantle. This feature may contribute to the role
CAP A1 plays in both normal synaptic homeostasis and in the generation of
epileptiform phenomena in epileptic patients.
PMID- 29951915
TI - Effects of training with flow restriction on the exercise pressor reflex.
AB - PURPOSE: We hypothesized that 5 weeks of endurance training with blood flow
restriction (R-training), providing relative ischemia and stimulation of the
muscle chemoreflex, would decrease the exercise pressor reflex (EPR) when
compared to training with the same workload in a free-flow condition (NR
training). METHODS: 10 subjects performed one-leg knee-extension training four
times a week during a 5-week period. Both legs were trained with identical
workload, with one leg being trained during flow-restriction induced by lower
body positive pressure. The EPR was assessed by measuring the increase in heart
rate (HR) and mean arterial pressure (MAP) during an isometric knee extension of
35% of max torque for 90 s, this was done before (C), and after training in each
leg (R and NR, respectively). RESULTS: At the end of isometric contraction, the
increase in mean AP (MAP) in the NR-trained leg and in the control condition were
41 +/- 4 and 38 +/- 4 mmHg, respectively, whereas the increase in the R-trained
leg was 30 +/- 4 mmHg (p < 0.05 R vs C and NR), corresponding to a decrease of
about 25%. A similar patter was observed with respect to responses in HR, where
the increase was 28 +/- 3 and 28 +/- 3 bpm in the NR and C, and 22 +/- 4 in the R
condition (p < 0.05 R vs C and NR). CONCLUSIONS: Peripheral metabolic changes
induced by relative ischemia are important in modifying the EPR in response to
exercise training.
PMID- 29951917
TI - Sub-circuit alterations in dorsal hippocampus structure and function after global
neurodevelopmental insult.
AB - Patients with neuropsychiatric and neurological disorders often express limbic
circuit abnormalities and deficits in information processing. While these
disorders appear to have diverse etiologies, their common features suggest
neurodevelopmental origins. Neurodevelopment is a prolonged process of diverse
events including neurogenesis/apoptosis, axon pathfinding, synaptogenesis, and
pruning, to name a few. The precise timing of the neurodevelopmental insult to
these processes likely determines the resulting functional outcome. We used the
epilepsy and schizophrenia-related gestational day 17 methylazoxymethanol acetate
model to examine the impact of this timed neurodevelopmental insult on principal
cell morphology and synaptic network function of the dorsal hippocampus (dHPC)
circuit. Our observed structural and functional alterations in dHPC are
compartment specific, indicating that adverse global exposure during gestation
can produce specific alterations and distort information processing in neural
circuits that underlie cognitive abilities.
PMID- 29951918
TI - Age-related macular degeneration affects the optic radiation white matter
projecting to locations of retinal damage.
AB - We investigated the impact of age-related macular degeneration (AMD) on visual
acuity and the visual white matter. We combined an adaptive cortical atlas and
diffusion-weighted magnetic resonance imaging (dMRI) and tractography to separate
optic radiation (OR) projections to different retinal eccentricities in human
primary visual cortex. We exploited the known anatomical organization of the OR
and clinically relevant data to segment the OR into three primary components
projecting to fovea, mid- and far-periphery. We measured white matter tissue
properties-fractional anisotropy, linearity, planarity, sphericity-along the
aforementioned three components of the optic radiation to compare AMD patients
and controls. We found differences in white matter properties specific to OR
white matter fascicles projecting to primary visual cortex locations
corresponding to the location of retinal damage (fovea). Additionally, we show
that the magnitude of white matter properties in AMD patients' correlates with
visual acuity. In sum, we demonstrate a specific relation between visual loss,
anatomical location of retinal damage and white matter damage in AMD patients.
Importantly, we demonstrate that these changes are so profound that can be
detected using magnetic resonance imaging data with clinical resolution. The
conserved mapping between retinal and white matter damage suggests that retinal
neurodegeneration might be a primary cause of white matter degeneration in AMD
patients. The results highlight the impact of eye disease on brain tissue, a
process that may become an important target to monitor during the course of
treatment.
PMID- 29951920
TI - [Joint pain and consumption of analgesics among young elite athletes : Nationwide
data from youth basketball].
AB - BACKGROUND: Joint pain may be an early indicator of biomechanical stress. During
adolescence the physical development, including the development of the
musculoskeletal system, is still ongoing and joint pain requires special
attention, especially among young athletes. OBJECTIVE: Young athletes from the
highest national basketball leagues in Germany were questioned about prevalence,
location, context and coping strategies concerning joint pain. MATERIAL AND
METHODS: Data were derived from the German "Adolescents' and Childrens' Health in
Elite Basketball study" (ACHE study). Analyses were based on an online survey of
182 elite basketball players between 13 and 19 years of age from 46 German teams,
conducted between April 2016 and June 2016. RESULTS: In the highest German
leagues 2 out of 3 players suffered from joint pain at the time of the survey (7
day prevalence 64.6%). Pain in the lower extremities occurred most frequently.
The 7-day prevalence for knee and leg pain reached up to 40% and foot pain up to
21%. For 84% of all players, occasional consumption of analgesics was the norm
and 40% took them frequently. The consumption of several medicinal substances,
especially of cyclooxygenase inhibitors, such as ibuprofen and diclofenac, is
widespread among adolescent elite basketball players as 1 out of 7 athletes (13%)
used medicinal substances despite being pain-free and 5% used it prophylactically
with the purpose of preventing pain. CONCLUSION: From the point of view of pain
medicine, it is not only the high prevalence of pain that is remarkable but also
the widespread use of analgesics without a prescription and the misguided
conception of adolescent competitive athletes that such medications have
preventive effects.
PMID- 29951919
TI - Diagnosis and Management of Acral Lentiginous Melanoma.
AB - OPINION STATEMENT: Melanoma is one of the most aggressive malignant skin tumors
and its incidence has been increasing worldwide in recent decades. Among the four
subtypes, acral lentiginous melanoma (ALM) shows the highest incidence in Asian
countries, whereas ALM comprises only 1% of all melanomas in white populations.
Early clinical diagnosis of ALM is essential, but early ALM lesions are often
difficult to diagnose because the pigmentation of the lesions sometimes follows
the skin marking of the palms and soles, resulting in an asymmetrical appearance
and an irregular border in both ALM and benign melanocytic nevus. To overcome
this difficulty, dermoscopy was introduced, and determination of the patterns by
this method is essential for accurate clinical diagnosis of ALM. Although recent
clinical trials have demonstrated that immune checkpoint inhibitors and BRAF/MEK
inhibitors showed significantly improved overall survival of patients with
advanced melanoma, ALM may be less susceptible to immune checkpoint inhibitors
because of the poor immune response to the tumor. Therefore, strategies for
enhancing the immune response to the tumor cells may be required when we apply
immune checkpoint inhibitors in advanced ALM. In this context, imiquimod,
dacarbazine, or interferon are possible therapies that may enhance the
effectiveness of the immune checkpoint inhibitors. In addition to being known to
have poor immunogenicity, ALM is also known to have infrequent BRAF mutation.
Therefore, the majority of ALM patients may not benefit from therapy with
BRAF/MEK inhibitors. However, some ALMs have mutations such as KIT and NRAS
mutations, and therefore, targeted therapies may improve the survival of ALM
patients in the future.
PMID- 29951921
TI - N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) as a Diagnostic
Biomarker of Left Ventricular Systolic Dysfunction in Patients with Acute
Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD).
AB - INTRODUCTION: Left ventricular systolic dysfunction (LVSD) and cardiac
decompensation often accompany AECOPD. Differentiation between the two is
difficult and mainly relies on clinical and echocardiographic diagnostic
procedures. The value of biomarkers, such as NT-proBNP, as diagnostic tools is
still insufficiently investigated. The main goals of this trial were to
investigate the value of NT-proBNP as a diagnostic tool for LVSD in AECOPD
patients and determine its cut-off value which could reliably diagnose LVSD
during AECOPD. PATIENTS AND METHODS: This trial prospectively enrolled 209
patients with AECOPD. The patients were divided into four groups-AECOPD plus
chronic pulmonary heart disease (CPHD) with or without left ventricular
compromise (LVSD), and AECOPD patients without CPHD with or without LVSD. NT
proBNP was measured within first 48 h of hospitalization. RESULTS: Majority of
patients were male (61%) active smokers (41.6%), average age of 68 years. High
quality of echocardiography was obtained in 63.3 and 22.5% of the patients had
LVSD. Average value of NT-proBNP in patients with LVSD was 3303.2 vs. 1092.5
pg/mL in patients without LVSD. Significant differences in NT-proBNP value (p =
0.0001) were determined between observed patient groups. At the cut-off value of
1505 pg/mL, sensitivity, specificity, and positive and negative predictive values
are 76.6, 83.3, 57.1, and 92.47%, respectively. CONCLUSION: At the cut-off value
of 1505 pg/mL NT-proBNP could be used as a diagnostic marker for LVSD in acute
exacerbation of COPD.
PMID- 29951922
TI - MiR-146b protect against sepsis induced mice myocardial injury through inhibition
of Notch1.
AB - Myocardial dysfunction is a major cause of death in sepsis. MicroRNA-146b (miR
146b) has been reported to be related to myocardial disease. However, the role of
miR-146b in sepsis as well as myocardial injury is still unclear. Septic cardiac
dysfunction in mice was induced by cecal ligation and puncture (CLP) and miR-146b
was found increased significantly in the myocardium tissue of CLP mice. It was
found that up-regulation of miR-146b by agomiR injection suppressed expression of
IL-1beta in mice as well as myocardium apoptosis in CLP mice. However,
suppression of miR-146b by antagomiR injection had inverse effects. Notch1 was
identified as a target gene of miR-146b by bioinformatics analysis. And it was
verified that in cardiomyocytes, the decrease of miR146b led to increase of both
the mRNA and protein level of Notch1 and vice versa. In septic mice serum
stimulated cardiomyocytes, up-regulation of miR-146b decreased the level of
Notch1 and Hes1. The knockout of Notch1 in transgenic mice showed that the
deficiency of Notch1 improved myocardial injury induced by CLP operation. The
apoptosis of cardiomyocytes was relieved and the expression of IL-1beta was
decreased. In conclusion, miR-146b targets to Notch1 and protected cardiomyocytes
against inflammation and apoptosis.
PMID- 29951923
TI - Broadening the scope of epidemiologic dementia research.
PMID- 29951924
TI - The assessment and prediction of temporal variations in surface water quality-a
case study.
AB - In order to optimize the processes of sampling, monitoring, and management, the
initial aim of this paper was to develop a model for the definition and
prediction of temporal changes of water quality. In the case of the Morava River
Basin (Serbia), the patterns of temporal changes have been recognized by applying
different multivariate statistical techniques. The results of the conducted
cluster analysis are the indicators of the existence of the three monitoring
periods: the low-water, transitional, and high-water periods, which is in
accordance with changes in the water flow in the analyzed river basin. A
possibility of reducing the initial data set and recognizing the main pollution
sources was examined by carrying out the principal component/factor analysis. The
results indicate that the natural factor has a dominant influence in temporal
groups. In order to recognize the discriminatory water quality parameters, a
discriminant analysis (DA) was carried out. Conducting the DA enabled a
significant reduction in the data set by the extraction of two parameters (the
water temperature and electrical conductivity). Furthermore, the artificial
neural network technique was used for testing the possibility of predicting
changes in the values of the discriminant factors in the monitoring periods. The
reliability of this method for the prediction of temporal variations of both
extracted parameters within all temporal clusters has been proven.
PMID- 29951925
TI - [Target volume concepts in radiotherapy and their implications for imaging].
AB - CLINICAL ISSUE: Successful radiotherapy requires precise localization of the
tumor and requires high-quality imaging for developing a treatment plan. STANDARD
TREATMENT: Irradiation of the tumor region, including a safety margin. TREATMENT
INNOVATIONS: The target volume consists of the gross tumor volume (GTV)
containing visible parts of the tumor, the clinical target volume (CTV) covering
the GTV plus invisible tumor extensions, and the planning target volume (PTV) to
account for uncertainties. The non-GTV parts of the CTV are based on historical
patient data. The PTV margins are based on a calculation of possible
uncertainties during planning, setup, or treatment. Normal tissue deserves the
identical care in contouring, since its tolerance may limit the tumor dose,
taking into account the contours of organs at risk. Serial risk organs benefit
from defining a planning organ of risk volume (PRV) to better limit the dose
delivered to them. DIAGNOSTIC WORK-UP: The better the imaging, the more reliable
the definition of the GTV and treatment success will be. Multiple imaging
sequences are desirable to support the delineation of the tumor. They may result
in different CTVs that, depending on their tumor burden, may require different
doses. PERFORMANCE: The definition of standardized target volumes according to
the ICRU reports 50, 62, and 83 forms the basis for an individualized radiation
treatment planning according to unified criteria on a high-quality level.
ACHIEVEMENTS: Radio-oncology is by nature interdisciplinary, the diagnostic
radiologist being an indispensable team partner. A regular dialogue between the
disciplines is pivotal for target volume definition and treatment success.
PRACTICAL RECOMMENDATIONS: Imaging for target volume definition requires highest
quality imaging, the use of functional imaging methods and close cooperation with
a diagnostic radiologist experienced in this field.
PMID- 29951927
TI - Identification of marker genes and pathways specific to precancerous duodenal
adenomas and early stage adenocarcinomas.
AB - BACKGROUND: The mechanism behind the pathogenesis and carcinogenesis of these
neoplasms is not fully understood. The objective of this study was to identify
genetic markers and pathways specific to precancerous duodenal adenomas and early
stage adenocarcinomas through gene expression analysis. METHODS: Gene expression
profiling was performed in 4 pairs of duodenal adenoma/adenocarcinomas and
corresponding matched normal tissue. Genes with consistent expression differences
were identified and confirmed in 7 independent pairs. Gene set enrichment
analysis (GSEA) was performed to characterize gene expression profiles of
duodenal adenoma/adenocarcinomas, together with immunohistochemical staining of
candidate oncogenic genes. RESULTS: 626 probes consistently demonstrated over a
twofold expression difference between tumor-normal pairs. Reverse transcriptase
polymerase chain reaction of genes with the most prominent difference in
expression between tumors and normal mucosa (KLK7, KLK6, CEMIP, MMP7, KRT17,
LGR5, G6PC, S100G, APOA1) validated the results of gene expression analysis. GSEA
demonstrated a strong association between duodenal adenoma/adenocarcinomas with
colorectal adenomas (p < 10-5) and gene expression patterns seen after APC gene
knockout (p < 10-5), suggesting that the Wnt/beta-catenin pathway plays a crucial
role in the carcinogenesis of these neoplasms. Immunohistochemical staining of an
independent group of duodenal adenomas confirmed over-accumulation of beta
catenin in 80.0% (16/20). CONCLUSIONS: Precancerous duodenal adenomas and early
stage adenocarcinomas demonstrate gene expression characteristics with a strong
resemblance to colorectal adenomas. The results of this study strongly suggest
that upregulation of the Wnt/beta-catenin pathway is the major factor involved in
the initial stages of the carcinogenesis of duodenal adenocarcinomas.
PMID- 29951928
TI - Fiscal crises and personal troubles: the great recession in Ireland and family
processes.
AB - BACKGROUND: Social disadvantage is often associated with worse child
psychological adjustment which itself is implicated in educational failure and
poor adult social position. The family stress model holds that the association
between social disadvantage and psychological adjustment stems from the impact of
economic pressure on parental mental health mediated through the parent/child
relationship. METHODS: We take advantage of a natural experiment offered by the
'great recession' in Ireland between 2008 and 2012. Structural equation models
using causal modelling and Longitudinal data from the Growing Up in Ireland
cohort study are used to test whether the experience of recession in families
impacts on children's psychological adjustment and whether this occurs directly
or is mediated by the processes identified in the family stress model. RESULTS:
More than 70% of families experienced a reduction in income between 2008 and 2011
and 26% reported cutting back on basics such as clothing and food. Family
experience of recession was significantly associated with negative change in all
of the components of the family stress model, particularly parental mental
health. However, less than half of the effect of recession was mediated by the
processes of the family stress model. Tests showed that a model with a direct
effect of recession on child psychological adjustment provided a better fit to
the data. CONCLUSIONS: Recession and economic pressure had a significant effect
on child psychological adjustment, but only a minority of this effect was
indirect via the mental health of parents and parent/child relationship. The
family stress model only offers a partial account of the mechanisms through which
economic hardship impacts on families and children.
PMID- 29951929
TI - Social networks and symptomatic and functional outcomes in schizophrenia: a
systematic review and meta-analysis.
AB - PURPOSE: To conduct a systematic review and meta-analysis to examine the strength
of associations between social network size and clinical and functional outcomes
in schizophrenia. METHOD: Studies were identified from a systematic search of
electronic databases (EMBASE, Medline, PsycINFO, and Web of Science) from January
1970 to June 2016. Eligible studies included peer-reviewed English language
articles that examined associations between a quantitative measure of network
size and symptomatic and/or functional outcome in schizophrenia-spectrum
diagnoses. RESULTS: Our search yielded 16 studies with 1,929 participants. Meta
analyses using random effects models to calculate pooled effect sizes (Hedge's g)
found that smaller social network size was moderately associated with more severe
overall psychiatric symptoms (N = 5, n = 467, g = - 0.53, 95% confidence interval
(CI) = - 0.875, - 0.184, p = 0.003) and negative symptoms (N = 8, n = 577, g = -
0.75, 95% CI = - 0.997, - 0.512, p = 0.000). Statistical heterogeneity was
observed I2 = 63.04%; I2 = 35.75%,) which could not be explained by low-quality
network measures or sample heterogeneity in sensitivity analyses. There was no
effect for positive symptoms (N = 7, n = 405, g = - 0.19, 95% CI = 0.494, 0.110,
p = 0.213) or social functioning (N = 3, n = 209, g = 0.36, 95% CI = - 0.078,
0.801, p = 0.107). Narrative synthesis suggested that larger network size was
associated with improved global functioning, but findings for affective symptoms
and quality of life were mixed. CONCLUSION: Psychosocial interventions which
support individuals to build and maintain social networks may improve outcomes in
schizophrenia. The review findings are cross-sectional and thus causal direction
cannot be inferred. Further research is required to examine temporal associations
between network characteristics and outcomes in schizophrenia and to test
theoretical models relating to explanatory or mediating mechanisms.
PMID- 29951926
TI - Clinical guidelines for primary sclerosing cholangitis 2017.
AB - BACKGROUND: Primary sclerosing cholangitis (PSC) is relatively rare disease and
pathogenesis and methods of treatments were still not established. Then, we had
conducted the making clinical guidelines to manage patients with PSC based on the
literature review and expert opinions. These clinical guidelines were made for
the medical doctors on the management of PSC, except child case of PSC. METHODS:
We had employed modified Delphi method. The production committee decided
guidelines, strength of recommendations and evidence level after reviewed
literatures systematically, and The Expert panel evaluated those. The Scientific
Committee of the Japan Biliary Association (JBA) evaluated revised guidelines,
and the Public comments were collected on web site of JBA. RESULTS: We had made
16 guidelines about epidemiology/pathophysiology, diagnostics, therapy and
prognosis. Also, we had made both diagnostic and therapeutic flow chart.
CONCLUSIONS: We hope that these guidelines will contribute to the improvement and
development of the medical care of PSC.
PMID- 29951930
TI - Effect of obesity on outcomes in patients who undergo implantation of a
continuous-flow left ventricular assist device.
PMID- 29951931
TI - Risk analysis using the prognostic nutritional index in hemodialysis-dependent
patients undergoing cardiac surgery.
AB - The prognostic nutritional index is an effective prognostic tool used in
gastrointestinal surgeries. However, its value has not been verified in
cardiovascular surgeries. This study aimed to investigate its utility in
hemodialysis-dependent patients undergoing cardiac surgery. We retrospectively
reviewed data of 110 hemodialysis-dependent patients who underwent cardiac
surgery between January 2006 and July 2016. 20 variables were evaluated for short
and long-term mortality prediction. Patients were divided into high and low
prognostic nutritional index groups with values > 34 (n = 90) and <= 34 (n = 20),
respectively. Preoperative characteristics and surgical outcomes were compared
between both groups. Overall, the in-hospital mortality rate was 9% (n = 10) and
the 1-, 3-, and 5-year actual survival rates were 69%, 58%, and 40%,
respectively. Univariate analysis for hospital death revealed age >= 70 years,
body mass index <= 18 kg/m2, total cholesterol <= 120 mg/dl, concomitant
procedures, albumin concentration <= 3.0 g/dl, and prognostic nutritional index
<= 34 as risk factors. Multivariate logistic regression analysis confirmed age >=
70 years and concomitant procedures as independent risk factors. Whereas ejection
fraction <= 30% and prognostic nutritional index <= 34 were strong independent
predictors of long-term death. Patients in the low prognostic nutritional index
group had significantly longer postoperative hospitalization, higher incidence of
complications, significantly higher in-hospital mortality rate, and significantly
lower actual survival rate. The low prognostic nutritional index affected
surgical outcomes in hemodialysis-dependent patients undergoing cardiac surgery.
Perioperative nutrition management based on the prognostic nutritional index may
improve surgical outcomes.
PMID- 29951932
TI - Minocycline Promotes BDNF Expression of N2a Cells via Inhibition of miR-155
Mediated Repression After Oxygen-Glucose Deprivation and Reoxygenation.
AB - Minocycline, an anti-infective agent of a tetracycline derivative, is reported to
improve behavioral functional recovery after cerebral ischemia via enhancing the
levels of brain-derived neurotrophic factor (BDNF). However, the precise
mechanisms that minocycline targets to enhance the expression of BDNF are not
fully defined. In the present study, we observed the neuroprotective effect and
its potential mechanisms of minocycline using oxygen-glucose
deprivation/reoxygenation (OGD/R)-treated N2a cells. We found that 50 uM
minocycline protected against neuronal apoptosis induced by OGD/R injury, with
increased expression ratio of Bcl-2/Bax and reduced expression of caspase-3.
Interestingly, minocycline resulted in the up-regulation of only BDNF protein,
not BDNF mRNA in N2a cells treated with OGD/R. Furthermore, we found that
minocycline inhibited OGD/R-induced up-regulation of miR-155 targeted BDNF
transcripts. Moreover, miR-155 mimic could partially abolish the neuroprotective
effects of minocycline via inhibiting the levels of BDNF protein. These findings
suggest that minocycline is neuroprotective against ischemic brain injury through
their modulation of miR-155-mediated BDNF repression.
PMID- 29951933
TI - The diagnostic value of TROP-2, SLP-2 and CD56 expression in papillary thyroid
carcinoma.
AB - OBJECTIVE: The study aimed to explore some novel diagnostic biomarkers for
papillary thyroid carcinoma (PTC) by identifying the different expression of TROP
2, SLP-2 and CD56 in benign and malignant thyroid lesions. METHODS: We evaluated
the mRNA expressions of TROP-2 and SLP-2 in fine needle aspirates (FNAs) which
contained 10 PTCs and 10 benign follicular adenomas (FAs) using quantitative real
time PCR (qRT-PCR). Immunohistochemical (IHC) staining of TROP-2, SLP-2 and CD56
was also performed on postoperative samples of 30 PTCs and 29 FAs. Membranous or
cytoplasmic staining in > 10% of cells was considered as positive. Diagnostic
sensitivity, specificity, positive predictive value, negative predictive value
(NPV) and diagnostic accuracy of these three biomarkers were carried out. We
further analyzed the associations between the clinical features and the
expressions of markers in PTCs. RESULTS: The mRNA expressions of both TROP-2 and
SLP-2 were increased substantially in PTCs in comparison with those in FAs (P <
0.05). Similarly, IHC for these two proteins demonstrated higher positive
staining in PTCs than in FAs (96.5% vs. 12.5% for TROP-2, 83.3% vs. 20.7% for SLP
2, P < 0.05). Conversely, CD56 expression was lost with 86.7% of PTCs. In
identifying malignancy, TROP-2 was the most sensitive marker and CD56 was the
most specific one. When the markers were combined, the sensitivity and NPV
increased to 100% and had better diagnostic accuracy. However, no association was
found between biomarker expressions and clinicopathological factors in PTCs.
CONCLUSIONS: We found that TROP-2, SLP-2 and CD56 were effective diagnostic
markers for PTC, especially when they were combined to use.
PMID- 29951934
TI - Nontuberculous mycobacterial disease managed within UK primary care, 2006-2016.
AB - Previous UK studies investigating nontuberculous mycobacteria have been limited
to reporting isolation from culture, not burden of disease. We assessed the
burden of nontuberculous mycobacterial disease (NTMD) in UK primary care from
2006 to 2016. Using electronic healthcare records, we identified patients with
NTMD using a strict definition including patients with guideline-directed
treatment/monitoring. We described treatment regimens and incidence/prevalence in
the general population and in patients with underlying chronic respiratory
diseases. Incidence of primary care-managed NTMD in the general population
decreased (2006 to 2016 rates per 100,000 person-years, 3.85 to 1.28). Average
annual prevalence of NTMD in the general population was 6.38 per 100,000. Around
85% were taking antimycobacterial therapy; 53.2% were taking a guideline
recommended regimen. Incidence of NTMD in patients with respiratory disease
decreased (2006 to 2016 rates per 100,000 person-years, 12.5 to 7.40). Average
annual prevalence of NTMD in patients with respiratory disease was 27.7 per
100,000. This is the first UK study using nationally representative data to
investigate the burden of NTMD managed within primary care. Incidence and
prevalence of managed NTMD within primary care is gradually declining. Increasing
complexity in the management of NTMD may be driving a shift in care to secondary
settings.
PMID- 29951935
TI - Determinants of Employment Outcome for the People with Schizophrenia Using the
WHODAS 2.0.
AB - Purpose Since the vocational outcomes of people with schizophrenia should be
viewed in a holistic way, the second edition of the World Health Organization
Disability Assessment Schedule (WHODAS 2.0) might provide an evaluation regarding
employment potential. To determine whether the WHODAS 2.0 scores can be used to
predict employment status, we examined the probabilistic cut-off values of the
scores and analyzed the relationship between work status and demographic
characteristics. Methods We selected 31,793 people aged between 18 and 65 with
schizophrenia or schizoaffective disorder from the disability evaluation database
in Taiwan and separated them into two groups based on employment status (employed
and unemployed). We used logistic regression to explore the association between
employment and demographic characteristics. Moreover, we conducted a receiver
operating characteristic (ROC) analysis to determine the cut-off point to assist
in determining employment potential based on the WHODAS 2.0 score. Results Among
the 31,793 participants, 3367 were employed and 18,801 were unemployed. The
unemployed participants accounted for a higher percentage of disability in each
domain of the WHODAS. The ROC analysis revealed that the optimal cut-off point of
the WHODAS score to distinguish the people who were employed and unemployed was
25.78 (area under curve = 0.80). Conclusions The present study indicated that
work status can be determined by the total score across the six domains of the
WHODAS score. Furthermore, the probability of employment may be determined
initially by the cut-off point of the WHODAS score in order to economize
evaluation time and prepare prevocational training for those with scores above
25.78.
PMID- 29951936
TI - A priori dietary patterns and blood pressure in the EPIC Florence cohort: a cross
sectional study.
AB - PURPOSE: Several foods and nutrients have been independently associated with
systolic (SBP) and diastolic (DBP) blood pressure values. This study aimed to
evaluate the effects of combined dietary habits on SBP and DBP values in a large
cohort of healthy adults, with a cross-sectional design. Adherence of
participants to four a priori dietary patterns was considered: the Healthy Eating
Index 2010 (HEI-2010); the Dietary Approaches to Stop Hypertension (DASH); the
Greek Mediterranean Diet Score (MDS); and the Italian Mediterranean Index (IMI).
METHODS: Overall, 13,597 volunteers (35-64 years) were enrolled in 1993-1998 in
the EPIC-Florence cohort. Information on dietary habits, anthropometry, smoking
status, education, physical activity habits, previous diagnosis of hypertension
and SBP and DBP measurements were collected at baseline. Multivariate regression
models were performed on 10,163 individuals (7551 women) after excluding subjects
with prevalent hypertension. RESULTS: IMI, DASH and HEI-2010 were significantly
and inversely associated with SBP and DBP values in the total population. The
strongest association emerged between IMI and SBP (beta - 1.80 excellent
adherence vs low adherence, 95% CI - 2.99; - 0.61, p trend 0.001) and DBP (beta -
1.12, 95% CI - 1.869; - 0.39, p trend 0.001) values. In sub-group analyses, an
inverse association also emerged between IMI and SBP and DBP values among females
and between DASH and DBP among males. MDS was not associated with SBP or DBP.
CONCLUSION: Overall, this study, carried out in a large cohort of healthy adults
from Tuscany (Central Italy), showed inverse significant associations between
specific a priori dietary patterns, identifying general models of health
conscious diet, and blood pressure values.
PMID- 29951937
TI - Diet quality scores in relation to metabolic risk factors in Japanese adults: a
cross-sectional analysis from the 2012 National Health and Nutrition Survey,
Japan.
AB - OBJECTIVE: Associations between the overall quality of Japanese diets and
metabolic risk factors are largely unknown. This cross-sectional study
investigated this issue using data from the 2012 National Health and Nutrition
Survey, Japan. METHODS: Dietary intake was assessed by a 1-day weighed dietary
record in 15,618 Japanese adults aged >= 20 years. Overall diet quality was
assessed by adherence to the Japanese Food Guide Spinning Top (JFG score), its
modified version (modified JFG score), the Mediterranean diet score (MDS) and the
Dietary Approaches to Stop Hypertension (DASH) score. Metabolic risk factors
included BMI, waist circumference, blood pressure, total, HDL- and LDL
cholesterol and glycated haemoglobin. RESULTS: While DASH score was consistently
associated with favourable nutrient intake patterns (including higher
micronutrient and dietary fibre intakes and lower SFA and sodium intakes), other
scores were associated with both favourable and unfavourable aspects (e.g., lower
micronutrient intakes for JFG score, higher SFA intakes for modified JFG score
and higher sodium intakes for MDS). The associations with metabolic risk factors
were also inconsistent and unexpected, including positive associations of JFG and
modified JFG scores with LDL-cholesterol, inverse associations of MDS with HDL
cholesterol and null associations of DASH score with blood pressure. CONCLUSIONS:
This study did not show expected and consistent associations of the four
available diet quality scores with nutrient intakes and metabolic risk factors in
Japanese adults. This in turn suggests the need for a scientific base on which to
develop an appropriate tool for assessing the quality of diets in the Japanese
context.
PMID- 29951938
TI - Towards computer-assisted TTTS: Laser ablation detection for workflow
segmentation from fetoscopic video.
AB - PURPOSE: Intrauterine foetal surgery is the treatment option for several
congenital malformations. For twin-to-twin transfusion syndrome (TTTS),
interventions involve the use of laser fibre to ablate vessels in a shared
placenta. The procedure presents a number of challenges for the surgeon, and
computer-assisted technologies can potentially be a significant support. Vision
based sensing is the primary source of information from the intrauterine
environment, and hence, vision approaches present an appealing approach for
extracting higher level information from the surgical site. METHODS: In this
paper, we propose a framework to detect one of the key steps during TTTS
interventions-ablation. We adopt a deep learning approach, specifically the
ResNet101 architecture, for classification of different surgical actions
performed during laser ablation therapy. RESULTS: We perform a two-fold cross
validation using almost 50 k frames from five different TTTS ablation procedures.
Our results show that deep learning methods are a promising approach for ablation
detection. CONCLUSION: To our knowledge, this is the first attempt at automating
photocoagulation detection using video and our technique can be an important
component of a larger assistive framework for enhanced foetal therapies. The
current implementation does not include semantic segmentation or localisation of
the ablation site, and this would be a natural extension in future work.
PMID- 29951940
TI - How to distinguish medicalization from over-medicalization?
AB - Is medicalization always harmful? When does medicine overstep its proper
boundaries? The aim of this article is to outline the pragmatic criteria for
distinguishing between medicalization and over-medicalization. The consequences
of considering a phenomenon to be a medical problem may take radically different
forms depending on whether the problem in question is correctly or incorrectly
perceived as a medical issue. Neither indiscriminate acceptance of medicalization
of subsequent areas of human existence, nor criticizing new medicalization cases
just because they are medicalization can be justified. The article: (i)
identifies various consequences of both well-founded medicalization and over
medicalization; (ii) demonstrates that the issue of defining appropriate limits
of medicine cannot be solved by creating an optimum model of health; (iii)
proposes four guiding questions to help distinguish medicalization from over
medicalization. The article should foster a normative analysis of the phenomenon
of medicalization and contribute to the bioethical reflection on the boundaries
of medicine.
PMID- 29951941
TI - Effect of temperature on elastic properties of CNT-polyethylene nanocomposite and
its interface using MD simulations.
AB - This paper investigates the effect of temperature on the elastic modulus of
carbon nanotube-polyethylene (CNT-PE) nanocomposite and its interface using
molecular dynamics (MD) simulations, by utilizing the second-generation polymer
consistent force field (PCFF). Two CNTs-armchair and zigzag-were selected as
reinforcing nano-fillers, and amorphous PE was used as the polymer matrix. For
atomistic modelling of the nanocomposite, the commercially available code
Materials Studio 8.0 was used and all other MD simulations were subsequently
performed using the open source code Large-Scale Atomic/Molecular Massively
Parallel Simulator (LAMMPS). To obtain the elastic modulus of the nanocomposite,
stress-strain curves were drawn at different temperatures by performing uniaxial
deformation tests on the nanocomposite material, whereas the curvatures of the
interfacial interaction energy vs. strain curves were utilized to obtain Young's
modulus of the interface. In addition, the glass transition temperatures of the
polymer matrix and nanocomposites were also evaluated using density-temperature
curves. Based on the results, it is concluded that, irrespective of temperature
condition, a nanocomposite reinforced with CNT of larger chirality (i.e.,
armchair) yields a higher value of Young's modulus of the nanocomposite and its
interface. It was also found that, at the phase transition (from a glassy to a
rubbery state) temperature (i.e., glass transition temperature), Young's moduli
of the polymer matrix, nanocomposite, and its interface drop suddenly. The
results obtained from MD simulations were verified with results obtained from
continuum-based rule-of-mixtures.
PMID- 29951939
TI - A synoptic survey of select wastewater-tracer compounds and the pesticide
imidacloprid in Florida's ambient freshwaters.
AB - Current wastewater treatment technologies do not remove many unregulated
hydrophilic compounds, and there is growing interest that low levels of these
compounds, referred to as emerging contaminants, may impact human health and the
environment. A probabilistic-designed monitoring network was employed to infer
the extent of Florida's ambient freshwaters containing the wastewater (Includes
reuse water, septic systems leachate, and wastewater treatment effluent.)
indicators sucralose, acetaminophen, carbamazepine, and primidone and those
containing the widely used pesticide imidacloprid. Extent estimates with 95%
confidence bounds are provided for canals, rivers, streams, small and large
lakes, and unconfined aquifers containing ultra-trace concentrations of these
compounds as based on analyses of 2015 sample surveys utilizing 528 sites.
Sucralose is estimated to occur in greater than 50% of the canal, river, stream,
and large lake resource extents. The pharmaceuticals acetaminophen,
carbamazepine, and primidone are most prevalent in rivers, with approximately 30%
of river kilometers estimated to contain at least one of these compounds.
Imidacloprid is estimated to occur in 50% or greater of the canal and river
resource extents, and it is the only compound found to exceed published toxicity
or environmental effects standards. Geospatial analyses show sucralose detection
frequencies within Florida's drainage basins to be significantly related to the
percentage of urban land use (R2 = 0.36, p < 0.001), and imidacloprid detection
frequencies to be significantly related to the percentage of urban and
agricultural land use (R2 = 0.47, p < 0.001). The extent of the presence of these
compounds highlights the need for additional emerging contaminant studies
especially those examining effects on aquatic biota.
PMID- 29951942
TI - Photobiomodulation for Global Cerebral Ischemia: Targeting Mitochondrial Dynamics
and Functions.
AB - Hypothermia is currently the only approved therapy for global cerebral ischemia
(GCI) after cardiac arrest; however, it unfortunately has multiple adverse
effects. As a noninvasive procedure, photobiomodulation (PBM) therapy has emerged
as a potential novel treatment for brain injury. PBM involves the use of low
level laser light therapy to influence cell behavior. In this study, we evaluated
the therapeutic effects of PBM treatment with an 808-nm diode laser initiated 6 h
after GCI. It was noted that PBM dose-dependently protected against GCI-induced
neuronal death in the vulnerable hippocampal CA1 subregion. Functional
assessments demonstrated that PBM markedly preserved both short-term (a week) and
long-term (6 months) spatial learning and memory function following GCI. Further
mechanistic studies revealed that PBM post-treatment (a) preserved healthy
mitochondrial dynamics and suppressed substantial mitochondrial fragmentation of
CA1 neurons, by reducing the detrimental Drp1 GTPase activity and its
interactions with adaptor proteins Mff and Fis1 and by balancing mitochondrial
targeting fission and fusion protein levels; (b) reduced mitochondrial oxidative
damage and excessive mitophagy and restored mitochondrial overall health status
and preserved mitochondrial function; and (c) suppressed mitochondria-dependent
apoptosome formation/caspase-3/9 apoptosis-processing activities. Additionally,
we validated, in an in vitro ischemia model, that cytochrome c oxidase served as
a key PBM target for mitochondrial function preservation and neuroprotection. Our
findings suggest that PBM serves as a promising therapeutic strategy for the
functional recovery after GCI, with mechanisms involving PBM's preservation on
mitochondrial dynamics and functions and the inhibition of delayed apoptotic
neuronal death in GCI.
PMID- 29951943
TI - RNA Sequencing of Carboplatin- and Paclitaxel-Resistant Endometrial Cancer Cells
Reveals New Stratification Markers and Molecular Targets for Cancer Treatment.
AB - Despite advances in surgical technique and adjuvant treatment, endometrial cancer
has recently seen an increase in incidence and mortality in the USA. The majority
of endometrial cancers can be cured by surgery alone or in combination with
adjuvant chemo- or radiotherapy; however, a subset of patients experience
recurrence for reasons that remain unclear. Recurrence is associated with
chemoresistance to carboplatin and paclitaxel and consequentially, high
mortality. Understanding the pathways involved in endometrial cancer
chemoresistance is paramount for the identification of biomarkers and novel
molecular targets for this disease. Here, we generated the first matched pairs of
carboplatin-sensitive/carboplatin-resistant and paclitaxel-sensitive/paclitaxel
resistant endometrial cancer cells and subjected them to bulk RNA sequencing
analysis. We found that 45 genes are commonly upregulated in carboplatin- and
paclitaxel-resistant cells as compared to controls. Of these, the leukemia
inhibitory factor, (LIF), the protein tyrosine phosphatase type IVA, member 3
(PTP4A3), and the transforming growth factor beta 1 (TGFB1) showed a highly
significant correlation between expression level and endometrial cancer overall
survival (OS) and can stratify the 545 endometrial cancer patients in the TCGA
cohort into a high-risk and low-risk-cohorts. Additionally, four genes within the
45 upregulated chemoresistance-associated genes are ADAMTS5, MICAL2, STAT5A, and
PTP4A3 codes for proteins for which small-molecule inhibitors already exist. We
identified these proteins as molecular targets for chemoresistant endometrial
cancer and showed that treatment with their correspondent inhibitors effectively
killed otherwise chemoresistant cells. Collectively, these findings underline the
utility of matched pair of chemosensitive and chemoresistant cancer cells to
identify markers for endometrial cancer risk stratification and to serve as a
pharmacogenomics model for identification of alternative chemotherapy approaches
for treatment of patients with recurrent disease.
PMID- 29951944
TI - Abnormalities of Mitochondrial Dynamics in the Failing Heart: Normalization
Following Long-Term Therapy with Elamipretide.
AB - PURPOSE: Abnormalities of MITO dynamics occur in HF and have been implicated in
disease progression. This study describes the broad range abnormalities of
mitochondrial (MITO) dynamics in Heart Failure with reduced ejection fraction
(HF) and evaluates the effects of long-term therapy with elamipretide (ELAM), a
MITO-targeting peptide, on these abnormalities. METHODS: Studies were performed
in left ventricular tissue from dogs and humans with HF, and were compared with
tissue from healthy dogs and healthy donor human hearts. Dogs with HF were
randomized to 3 months therapy with ELAM or vehicle. The following were evaluated
in dog and human hearts: (1) regulators of MITO biogenesis, including endothelial
nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP), and
peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha,
a transcription factor that drives MITO biogenesis); (2) regulators of MITO
fission and fusion, including fission-1, dynamin-related protein-1, mitofusion-2,
dominant optic atrophy-1, and mitofilin; and (3) determinants of cardiolipin (CL)
synthesis and remodeling, including CL synthase-1, tafazzin-1, and acyl
CoA:lysocardiolipin acyltransferase-1. RESULTS: The study showed decreased levels
of eNOS, cGMP, and PGC-1alpha in HF (dog and human). Increased levels of fission
associated proteins, decreased levels of fusion-associated proteins, decreased
mitofilin, and abnormalities of CL synthesis and remodeling were also observed.
In all instances, these maladaptations were normalized following long-term
therapy with ELAM. CONCLUSIONS: Critical abnormalities of MITO dynamics occur in
HF and are normalized following long-term therapy with ELAM. The findings provide
support for the continued development of ELAM for the treatment of HF.
PMID- 29951945
TI - [Heart failure networks and centers : What does everyday life look like?]
AB - The German Cardiac Society (DGK) and the German Society for Thoracic and
Cardiovascular Surgery (DGTHG) jointly advocated the initiation and certification
of heart failure (HF) networks in a position statement in 2016. In these
networks, supraregional HF centers cooperate with specialized regional HF clinics
and registered cardiologists to improve intersectoral treatment of patients with
HF. So far predominantly supraregional HF centers have achieved certification but
more recently regional clinics as well as registered cardiologists have applied
for certification, now enabling the comprehensive establishment of HF networks.
In this article the background, the current situation and the future perspectives
of HF networks are assessed and approaches for better networking are discussed.
PMID- 29951946
TI - Optimal reperfusion strategy in patients with acute STEMI and multivessel disease
an updated meta-analysis.
AB - BACKGROUND: This meta-analysis compared the efficacy and safety of culprit-only
revascularization (COR) and complete revascularization (CR) in the treatment of
patients with acute ST-elevation myocardial infarction (STEMI) and multivessel
disease to determine the optimal reperfusion strategy. METHOD: We analyzed
published multicenter randomized controlled trials to compare COR and CR in
patients with acute STEMI and multivessel disease. The PubMed, Cochrane Library,
and Ovid databases were searched, and the meta-analysis was performed using
Review Manager 5.3 software. RESULTS: Eight multicenter randomized controlled
trials were selected involving 2870 patients, of whom 1604 underwent COR and 1266
underwent CR. No significant heterogeneity was identified across these selected
studies. The CR strategy significantly decreased the incidence of major adverse
cardiac events (MACE; odds ratio [OR]: 2.44, 95% CI [95% confidence interval]:
1.96-3.03, p < 0.001), mortality (OR: 1.76, 95% CI: 1.25-2.47, p = 0.001),
myocardial infarction (MI, OR: 1.62, 95% CI: 1.12-2.35, p = 0.01), and repeat
revascularization (OR: 3.20, 95% CI: 2.41-4.24, p < 0.001) compared with the COR
approach. Moreover, no significant difference was identified in the safety
indexes, including contrast-induced nephropathy, stroke, and bleeding, between
the CR and the COR group (p > 0.05). CONCLUSION: The present meta-analysis
determined that CR is an efficacious and safe reperfusion strategy in patients
with acute STEMI and multivessel disease.
PMID- 29951947
TI - Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics,
Pathogenesis, and Treatment.
AB - Deficiency of ADA2 (DADA2) is the first molecularly described monogenic
vasculitis syndrome. DADA2 is caused by biallelic hypomorphic mutations in the
ADA2 gene that encodes the adenosine deaminase 2 (ADA2) protein. Over 60 disease
associated mutations have been identified in all domains of ADA2 affecting the
catalytic activity, protein dimerization, and secretion. Vasculopathy ranging
from livedo reticularis to polyarteritis nodosa (PAN) and life-threatening
ischemic and/or hemorrhagic stroke dominate the clinical features of DADA2.
Vasculitis and inflammation can affect many organs, explaining the intestinal,
hepatological, and renal manifestations. DADA2 should be primarily considered in
patients with early-onset fevers, rashes, and strokes even in the absence of
positive family history. Hematological manifestations include most commonly
hypogammaglobulinemia, although pure red cell aplasia (PRCA), immune
thrombocytopenia, and neutropenia have been increasingly reported. Thus, DADA2
may unify a variety of syndromes previously not thought to be related. The first
line treatment consists of TNF-inhibitors and is effective in controlling
inflammation and in preserving vascular integrity. Hematopoietic stem cell
transplantation (HSCT) has been successful in a group of patients presenting with
hematological manifestations. ADA2 is highly expressed in myeloid cells and plays
a role in the differentiation of macrophages; however, its function is still
largely undetermined. Deficiency of ADA2 has been linked to an imbalance in
differentiation of monocytes towards proinflammatory M1 macrophages. Future
research on the function of ADA2 and on the pathophysiology of DADA2 will improve
our understanding of the condition and promote early diagnosis and targeted
treatment.
PMID- 29951949
TI - The Deborah Danner Story: Officer-Involved Deaths of People Living with Mental
Illness.
PMID- 29951948
TI - Biweekly Hizentra(r) in Primary Immunodeficiency: a Multicenter, Observational
Cohort Study (IBIS).
AB - Immunoglobulin G (IgG) replacement therapy is a standard treatment for patients
with primary immunodeficiency diseases (PIDs). Hizentra(r), a 20% human
subcutaneous IgG (SCIG), is approved for biweekly administration for PIDs. The
aim of the multicenter IBIS study was to prospectively investigate the efficacy
of biweekly Hizentra(r) compared with previous IVIG or SCIG treatment regimens in
patients with PIDs. The study consisted of a 12-month retrospective period
followed by 12-month prospective observational period. The main endpoints
included pre-infusion IgG concentrations, proportion of patients with serious
bacterial infections (SBIs), other infections, hospitalizations due to PID
related illnesses, and days with antibiotics during the study periods. Of the 36
patients enrolled in the study, 35 patients continued the study (mean age 26.1 +/
14.4 years; 68.6% male). The mean pre-infusion IgG levels for prior
immunoglobulin regimens during the retrospective period (7.84 +/- 2.09 g/L) and
the prospective period (8.55 +/- 1.76 g/L) did not show any significant
variations (p = 0.4964). The mean annual rate of SBIs/patient was 0.063 +/- 0.246
for both prospective and retrospective periods. No hospitalizations related to
PIDs were reported during the prospective period versus one in the retrospective
period. All patients were either very (76.5%) or quite (23.5%) satisfied with
biweekly Hizentra(r) at the end of the study. In conclusion, the IBIS study
provided real-world evidence on the efficacy of biweekly Hizentra(r) in patients
with PIDs, thus verifying the data generated by the pharmacometric modeling and
simulation study in a normal clinical setting.
PMID- 29951950
TI - Evidence for the Validity of the Psychopharmacotherapy-Structured Clinical
Observation Tool: Results of a Factor and Time Series Analysis.
AB - OBJECTIVE: The Psychopharmacotherapy-Structured Clinical Observation (P-SCO) is a
direct observation tool designed to assess resident performance of a medication
visit. This study examines two dimensions of validity for the P-SCO: internal
structure and how scores correlate with another variable associated with
competence (experience). METHODS: The faculty completed 601 P-SCOs over 4 years.
Multilevel exploratory factor analysis was performed with minimum thresholds for
eigenvalue (>= 1.0) and proportion of variance explained (>= 5.0%). Internal
reliability was assessed with Cronbach alpha. To examine how scores changed with
experience, mean ratings (1-4 scale) were calculated for each factor by quarter
of the academic year. Separate linear mixed models were also performed. RESULTS:
The analysis yielded three factors that explained 50% of the variance and
demonstrated high internal reliability: affective tasks (alpha = 0.90), cognitive
tasks (alpha = 0.84), and hard tasks (alpha = 0.74). Items within "hard tasks"
were assessment of substance use, violence risk, and adherence, and inquiry about
interactions with other providers. Monitoring adverse effects did not load on the
hard task factor but also had overall low mean ratings. Compared to the first
quarter, fourth quarter scores for affective tasks (b = 0.54, p < 0.01) and hard
tasks (b = 0.46, p = 0.02) were significantly improved while cognitive tasks had
a non-significant increase. For the hard tasks, the proportion of residents with
a low mean rating improved but was still over 30% during the fourth quarter.
CONCLUSIONS: The results provide evidence for the validity of the P-SCO with
respect to its internal structure and how scores correlate with experience.
Curricular implications are explored, especially for the tasks that were hard to
learn.
PMID- 29951951
TI - Developmental engineering: design of clinically efficacious bioartificial tissues
through developmental and systems biology.
PMID- 29951952
TI - Synthetic genomes engineered by SCRaMbLEing.
PMID- 29951953
TI - Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone
producing pituitary adenomas.
AB - Currently, the primary therapeutic strategy for most growth hormone-producing
pituitary adenomas (GHPA) is surgery. Due to the invasiveness of GHPA, high
recurrence has limited the benefit of complete adenoma removal surgery. Epidermal
growth factor-like domain 7 (EGFL7) is a secreted factor implicated in tumor
angiogenesis, growth, invasiveness and metastasis in GHPA. Herein, we observed
that the expression level of EGFL7 and p-EGFR in invasive GHPA was much higher
than that of non-invasive GHPA. The overexpression of EGFL7 was positively
correlated with activation of EGFR (p-EGFR). Noticeably, EGFL7 knockdown
significantly inhibited activation of EGFR signaling cascades, including p-ERGR,
p-AKT and p-ERK. Further studies showed that EGFL7 knockdown or pharmacological
inhibition of EGFR-pathway, using EGFR inhibitor Tyrphostin AG-1478,
significantly suppressed migration and invasion of GH3 and GT1-1 cells. In
summary, our findings suggest that EGFL7 is a key factor for regulation of EGFR
signaling pathway and plays an important role in migration and invasion of
invasive GHPA.
PMID- 29951954
TI - Aquaporin 5 is degraded by autophagy in diabetic submandibular gland.
AB - Autophagy is a catabolic process which is involved in the development of many
diseases including diabetes mellitus and its complications. Hyposalivation is a
common complication of diabetes mellitus, whereas its mechanism remains unclear.
Here, we observed that the stimulated salivary flow rate of SMG was significantly
decreased in db/db mice, a diabetic mice model. The expressions of aquaporin 5
(AQP5), a water channel protein, were decreased, whereas the mRNA level of AQP5
was increased in SMGs of both diabetic patients and mice. Under transmission
electron microcope, more autophagosomes were detected in diabetic SMGs.
Expressions of autophagy related proteins LC3II, Beclin-1 and ATG5 were
increased, meanwhile autophagy substrate p62 was decreased in SMGs of diabetic
patients and mice, indicating that autophagy was activated in diabetic SMG.
Double immunofluorescence staining showed that the colocalization of AQP5 and LC3
was increased in SMGs of diabetic mice. In cultured SMG-C6 cells, high glucose
(HG), but not high osmotic pressure, reduced AQP5 protein expression and induced
autophagy. Moreover, inhibition of autophagy by 3-methyladenin, an autophagy
inhibitor, or by autophagy-related gene 5 siRNA, decreased HG-induced AQP5
reduction in SMG-C6 cells. Additionally, the expression of p-p85, p-Akt and p
mTOR were decreased in HG-treated SMG-C6 cells. Pretreatment with 740Y-P, a PI3K
agonist, significantly suppressed HG-induced autophagy and AQP5 degradation.
Taken together, these results indicate that autophagy plays a crucial role in
AQP5 degradation in diabetic SMG via PI3K/Akt/mTOR signaling pathway, which
contributes to the dysfunction of diabetic SMG. Our study provides a novel
mechanism of diabetic hyposalivation.
PMID- 29951955
TI - Correction to: Clinical characteristics and cardiovascular outcomes in patients
with atrial fibrillation receiving rhythm-control therapy: the Fushimi AF
Registry.
AB - In the original publication of the article, the data of Body mass index >= 25
(kg/m2)a is published incorrectly in Table 1. Since this is categorical variable,
the data should have been expressed as a number (percentage), not as mean +/-
standard deviation. The corrected version of Table 1 is as below.
PMID- 29951956
TI - Neurocysticercus on the Run.
PMID- 29951957
TI - Loss of Vestibular Ocular Reflex in Nonconvulsive Status Epilepticus.
AB - BACKGROUND: Electroencephalogram (EEG) findings of generalized periodic
discharges (GPDs) with triphasic morphology were introduced as a metabolic
phenomenon, but more recently have been associated with epileptic phenomenon.
Resolution of EEG findings along with clinical improvement from treatment is
diagnostic. The known causes of reversible, isolated loss of OVR include
medication toxicity, lead exposure, and thiamine deficiency, but its association
with nonconvulsive status epilepticus (NCSE) has never been published. Medication
induced loss of OVR resolves after a 24-hour washout period. We report a case of
reversible, isolated loss of vestibular ocular reflex (VOR) associated with
epileptic phenomenon. METHODS: This is a case report of a single patient.
RESULTS: A 74-year-old male with a history of complex partial seizures admitted
for a pneumonectomy had a post-operative course complicated by two instances of
coma, the latter associated with an isolated loss of VOR. EEG revealed GPDs with
triphasic morphology initially interpreted as a metabolic phenomenon. The
patient's mental status, exam and EEG findings improved after low dose infusion
of propofol for tracheostomy, and he was eventually discharged at baseline
neurological function. Due to this response, his coma, loss of VOR and EEG were
later interpreted as a consequence of NCSE. CONCLUSION: The interpretation of
GPDs with triphasic wave morphology range from metabolic phenomenon to NCSE. NCSE
should be highly considered on the differential for encephalopathy regardless of
the circumstances. NCSE may be a potential cause of reversible, isolated loss of
the VOR and an AED trial in the appropriate clinical context should be
considered. This is the first report of loss of VOR possibly associated with
NCSE.
PMID- 29951958
TI - A Systematic Review of Outcome Measures Employed in Aneurysmal Subarachnoid
Hemorrhage (aSAH) Clinical Research.
AB - Consensus on appropriate outcome measures to use in aneurysmal subarachnoid
hemorrhage (aSAH) research has not been established, although the transition
toward a core outcome set (COS) would provide significant benefits. To inform COS
development, we conducted a systematic review to identify outcome measures
included in reports of randomized clinical trials (RCTs) of interventions in
patients with aSAH. Ovid Medline, EMBASE, CINAHL, and CENTRAL were searched. RCTs
investigating aSAH published between January 1996 and May 2015 were included. The
primary and secondary outcomes of RCTs were recorded and classified according to
the OMERACT Consortium's framework. We identified 1093 potential studies of which
129 met inclusion criteria representing 24 238 patients. There were 285 unique
outcome measures. The Glasgow Outcome Scale (GOS) was the most frequently used
primary outcome (13/129, 10.1%). Mortality was reported in 84 trials (65.1%) with
3 months the most common time point (34/129, 26.4%). The GOS (65/129, 50.4%) and
the Modified Rankin Scale (51/129, 39.5%) were the most commonly reported
functional measures; however, these were reported at different time points and
often dichotomized using different ranges. Patient-reported quality of life
measures were used in 11 trials (8.5%). Transcranial Doppler was the most
frequently used imaging modality (40/129, 31.0%). Definitions and reporting of
vasospasm, delayed cerebral ischemia and imaging modality results were highly
variable. The marked heterogeneity of outcomes in reports of RCTs supports the
development of a core outcome set for aSAH trials. Our study has identified a
wide range of outcomes for potential inclusion in a future aSAH COS.
PMID- 29951959
TI - The Role of Serum Calcium Level in Intracerebral Hemorrhage Hematoma Expansion:
Is There Any?
AB - Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, with
a high rate of mortality and morbidity. Even with the best current medical or
surgical interventions, outcomes remain poor. The location and initial hematoma
volume are strong predictors of mortality. Hematoma expansion (HE) is a further
marker of poor prognosis that may be at least partly preventable. Several risk
factors for HE have been identified, including baseline ICH volume,
anticoagulation, and computed tomography angiography spot signs. Recent studies
have shown the correlation of serum calcium (Ca++) levels on admission with HE.
Low serum Ca++ level has been associated with larger hematoma volume at the time
of presentation, HE, and worse outcome. Although the causal and mechanistic links
between low serum Ca++ level and HE are not well understood, several mechanisms
have been proposed including coagulopathy, platelet dysfunction, and higher blood
pressure (BP) in the context of low serum Ca++ level. However, low serum Ca++
level might be only a biomarker of the adaptive response due to acute
inflammatory response following acute ICH. The purpose of the current review is
to discuss the evidence regarding the possible role of low serum Ca++ level on HE
in acute ICH.
PMID- 29951960
TI - Non-invasive Cerebrovascular Autoregulation Assessment Using the Volumetric
Reactivity Index: Prospective Study.
AB - BACKGROUND: This prospective study of an innovative non-invasive ultrasonic
cerebrovascular autoregulation (CA) monitoring method is based on real-time
measurements of intracranial blood volume (IBV) reactions following changes in
arterial blood pressure. In this study, we aimed to determine the clinical
applicability of a non-invasive CA monitoring method by performing a prospective
comparative clinical study of simultaneous invasive and non-invasive CA
monitoring on intensive care patients. METHODS: CA was monitored in 61 patients
with severe traumatic brain injuries invasively by calculating the pressure
reactivity index (PRx) and non-invasively by calculating the volumetric
reactivity index (VRx) simultaneously. The PRx was calculated as a moving
correlation coefficient between intracranial pressure and arterial blood pressure
slow waves. The VRx was calculated as a moving correlation coefficient between
arterial blood pressure and non-invasively-measured IBV slow waves. RESULTS: A
linear regression between VRx and PRx averaged per patients' monitoring session
showed a significant correlation (r = 0.843, p < 0.001; 95% confidence interval
0.751 - 0.903). The standard deviation of the difference between VRx and PRx was
0.192; bias was - 0.065. CONCLUSIONS: This prospective clinical study of the non
invasive ultrasonic volumetric reactivity index VRx monitoring, based on
ultrasonic time-of-flight measurements of IBV dynamics, showed significant
coincidence of non-invasive VRx index with invasive PRx index. The ultrasonic
time-of-flight method reflects blood volume changes inside the acoustic path,
which crosses both hemispheres of the brain. This method does not reflect locally
and invasively-recorded intracranial pressure slow waves, but the autoregulatory
reactions of both hemispheres of the brain. Therefore, VRx can be used as a non
invasive cerebrovascular autoregulation index in the same way as PRx and can also
provide information about the CA status encompassing all intracranial
hemodynamics.
PMID- 29951961
TI - Engineered Exosomes for Targeted Transfer of siRNA to HER2 Positive Breast Cancer
Cells.
AB - Exosomes are the best options for gene targeting, because of their natural,
nontoxic, non-immunogenic, biodegradable, and targetable properties. By
engineering exosome-producing cells, ligands can be expressed fusing with
exosomal surface proteins for targeting cancer cell receptors. In the present
study, HER2-positive breast cancer cells were targeted with a modified exosome
producing engineered HEK293T cell. For this purpose, the HEK293T cells were
transduced by a lentiviral vector bearing-LAMP2b-DARPin G3 chimeric gene. Stable
cells expressing the fusion protein were selected, and the exosomes produced by
these cells were isolated from the culture medium, characterized, and then loaded
with siRNA for subsequent delivery to the SKBR3 cells. Our results showed that
stable HEK293T cells produced DARPin G3 on the surface of exosomes. These
exosomes can bind specifically to HER2/Neu and are capable of delivering siRNA
molecules against TPD52 gene into SKBR3 cell line down-regulating the gene
expression up to 70%. Present approach is envisaged to facilitate genes and drugs
transfer to HER2 cancer cells providing additional option for gene therapy and
drug delivery.
PMID- 29951962
TI - ABCA1 Is Coordinated with ABCB1 in the Arsenic-Resistance of Human Cells.
AB - Arsenic is one of the most widespread global environmental toxicants associated
with endemic poisoning. ATP-binding cassette (ABC) proteins are transmembrane
channels that transport and dispose of lipids and metabolic products across the
plasma membrane. The majority of ABC family members (including ABCB1 and ABCC1)
are reported to play a role in the development of arsenic and drug resistance in
mammals. Previously, we established a human arsenic-resistant ECV-304 (AsRE) cell
line and identified ABCA1 as a novel arsenic resistance gene. In the current
study, we further investigated the potential contribution of ABCA1, ABCB1, and
ABCC1 to arsenic resistance through measurement of survival rates and arsenic
accumulation in AsRE cells with RNA interference. The arsenic resistance capacity
of ABCC1 was the strongest among the three genes, while those of ABCA1 and ABCB1
were similar. Double or triple gene knockdown of ABCA1, ABCB1, and ABCC1 via RNA
interference led to a decrease significant in arsenic resistance when ABCA1/ABCB1
or ABCB1/ABCC1 were simultaneously silenced. Interestingly, no differences were
evident between cells with ABCA1/ABCC1 and ABCC1 only knockdown. Our findings
suggest that ABCA1 and ABCB1 proteins display similar arsenic resistance
capabilities and possibly coordinate to promote arsenic resistance in AsRE cells.
PMID- 29951963
TI - Acquired angioedema in juvenile systemic lupus erythematosus: case-based review.
AB - An acquired form of angioedema that is clinically similar but scarcer than the
hereditary form may be caused, even more rarely, by the presence of an underlying
autoimmune disease. We report a previously healthy 16-year-old girl with an
acquired angioedema as a rare and initial presentation of systemic lupus
erythematosus. The patient had no previous angioedema attack and no family
history. She did not have any chronic diseases and did not use any medicine
regularly. The patient was diagnosed with systemic lupus erythematosus with the
presence of polyarthralgia, angioedema, leucopenia, and positivity of immunologic
criteria. Her edema resolved with high-dose methylprednisolone and
hydroxychloroquine slowly. In conclusion, new-onset angioedema in adolescent
girls should be investigated to evaluate autoimmunity and the possibility of
systemic lupus erythematosus. The related literature on acquired angioedema
associated with systemic lupus erythematosus is also reviewed.
PMID- 29951964
TI - C3 glomerulopathy in NLRP12-related autoinflammatory disorder: case-based review.
AB - Autoinflammatory diseases (AIDs) are a recently described group of conditions
caused by mutations in multiple genes that code for proteins of the innate immune
system. Cryopyrin-associated periodic syndromes (CAPS) are autoinflammatory
diseases comprising three clinically overlapping disorders: familial cold
urticarial syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset
multisystem inflammatory disease (NOMID). CAPS have been associated with gain-of
function variations in NLRP3 (NOD-like receptor family, pyrin containing domain
3). However, a new class of autoinflammatory disease resembling FCAS or MWS has
been described in patients with NLRP12 mutations. Here, we report a 6-year-old
boy diagnosed with AID who developed an unexpected C3 glomerulopathy during
attacks and carried a novel variation in NLRP12. Following treatment with IL
(interleukin) 1 targeting agents, all symptoms and inflammation resolved. This is
the first case in the literature affected by both autoinflammatory disease and C3
glomerulopathy.
PMID- 29951965
TI - Identification and genetic mapping for rht-DM, a dominant dwarfing gene in mutant
semi-dwarf maize using QTL-seq approach.
AB - Semi-dwarfism is an agronomically important trait in breeding for stable high
yields and for resistance to damage by wind and rain (lodging resistance). Many
QTLs and genes causing dwarf phenotype have been found in maize. However, because
of the yield loss associated with these QTLs and genes, they have been difficult
to use in breeding for dwarf stature in maize. Therefore, it is important to find
the new dwarfing genes or materials without undesirable characters. The
objectives of this study were: (1) to figure out the inheritance of semi-dwarfism
in mutants; (2) mapping dwarfing gene or QTL. Maize inbred lines '18599' and
'DM173', which is the dwarf mutant derived from the maize inbred line '173'
through 60Co-gamma ray irradiation. F2 and BC1F1 population were used for genetic
analysis. Whole genome resequencing-based technology (QTL-seq) were performed to
map dwarfing gene and figured out the SNP markers in predicted region using dwarf
bulk and tall bulk from F2 population. Based on the polymorphic SNP markers from
QTL-seq, we were fine-mapping the dwarfing gene using F2 population. In F2
population, 398 were dwarf plants and 135 were tall plants. Results of chi2 tests
indicated that the ratio of dwarf plants to tall plants was fitted to 3:1 ratio.
Furthermore, the chi2 tests of BC1F1 population showed that the ratio was fitted
to 1:1 ratio. Based on QTL-seq, the dwarfing gene was located at the region from
111.07 to 124.56 Mb of chromosome 9, and we named it rht-DM. Using traditional
QTL mapping with SNP markers, the rht-DM was narrowed down to 400 kb region
between SNP-21 and SNP-24. The two SNPs were located at 0.43 and 0.11 cM.
Segregation analysis of F2 and BC1F1 indicated that the dwarfing gene was likely
a dominant gene. This dwarfing gene was located in the region between 115.02 and
115.42 Mb on chromosome 9.
PMID- 29951966
TI - Ruptured renal artery in microscopic polyangiitis: a case report and literature
review.
AB - Medium-vessel hemorrhage is a rare occurrence in ANCA-associated vasculitis, and
has been previously described in only a few patients with microscopic
polyangiitis. We report a case of renal hemorrhage in a patient with microscopic
polyangiitis that was successfully managed by transcatheter arterial embolization
of the active bleeding sites. The early clinical findings included necrotizing
arteritis, as indicated by skin biopsy; rapidly progressive glomerulonephritis;
mononeuritis multiplex; positive screening for myeloperoxidase-specific
antineutrophil cytoplasmic antibody. Corticosteroid therapy was initiated. The
patient's health deteriorated at 1 week, with rapidly progressing anemia.
Computerized tomography identified a large, right-sided, perirenal hematoma, with
active bleeding. Bleeding was successfully managed via segmental embolization of
the renal artery. The patient was treated with steroid therapy and MZR, and
subsequently underwent maintenance hemodialysis treatment for end-stage renal
disease. Spontaneous renal hemorrhage is a rare but fatal clinical condition. A
ruptured renal artery should be considered in a patient with microscopic
polyangiitis, even in the absence of previous trauma and renal biopsy, when
unexplained anemia or signs of shock occur.
PMID- 29951967
TI - Characterization of Delta(G970-T1122)-CFTR, the most frequent CFTR mutant
identified in Japanese cystic fibrosis patients.
AB - A massive deletion over three exons 16-17b in the CFTR gene was identified in
Japanese CF patients with the highest frequency (about 70% of Japanese CF
patients definitely diagnosed). This pathogenic mutation results in a deletion of
153 amino acids from glycine at position 970 (G970) to threonine at 1122 (T1122)
in the CFTR protein without a frameshift. We name it Delta(G970-T1122)-CFTR. In
the present study, we characterized the Delta(G970-T1122)-CFTR expressed in CHO
cells using immunoblots and a super resolution microscopy. Delta(G970-T1122)-CFTR
proteins were synthesized and core-glycosylated but not complex-glycosylated.
This observation suggests that the Delta(G970-T1122) mutation can be categorized
into the class II mutation like DeltaF508. However, VX-809 a CFTR corrector that
can help maturation of DeltaF508, had no effect on Delta(G970-T1122).
Interestingly C-terminal FLAG tag seems to partially rescue the trafficking
defect of Delta(G970-T1122)-CFTR; however the rescued Delta(G970-T1122)-CFTR
proteins do not assume channel function. Japanese, and perhaps people in other
Asian nations, carry a class II mutation Delta(G970-T1122) with a higher
frequency than previously appreciated. Further study of the Delta(G970-T1122)
CFTR is essential for understanding CF and CFTR-related diseases particularly in
Asian countries.
PMID- 29951968
TI - Highly modular pattern in ant-plant interactions involving specialized and non
specialized myrmecophytes.
AB - Because Tachia guianensis (Gentianaceae) is a "non-specialized myrmecophyte"
associated with 37 ant species, we aimed to determine if its presence alters the
ant guild associated with sympatric "specialized myrmecophytes" (i.e., plants
sheltering a few ant species in hollow structures). The study was conducted in a
hilly zone of a neotropical rainforest where two specialized myrmecophytes grow
at the bottom of the slopes, another at mid-slope, and a fourth on the hilltops.
Tachia guianensis, which occurred everywhere, had its own guild of associated ant
species. A network analysis showed that its connections with the four other
myrmecophytes were rare and weak, the whole resulting in a highly modular pattern
of interactions with one module (i.e., subnetwork) per myrmecophyte. Three ant
species parasitized three out of the four specialized myrmecophytes (low
nestedness noted), but were not or barely associated with T. guianensis that
therefore did not influence the parasitism of specialized myrmecophytes.
PMID- 29951969
TI - The effect of participation in neoadjuvant clinical trials on outcomes in
patients with early breast cancer.
AB - BACKGROUND: Clinical trials can offer novel and more advanced and/or novel
treatments to cancer patients in advance of them being approved and available for
all patients. While several studies have examined the effect of clinical trial
participation on prognosis, there has been no clear conclusion from these
studies. Therefore, we chose to test the influence of trial participation on
pathological complete response (pCR) and mastectomy rates after neoadjuvant
chemotherapy. METHODS: In this retrospective study, all patients treated with
neoadjuvant chemotherapy from 2001 to 2014 were selected. A total of 1038
patients with complete treatment, patient, and tumor characteristics were
included. A total of 260 of those were treated in clinical trials. We examined
whether study participation status in addition to commonly known predictors for
pCR improves prediction of pCR. Similar analyses were conducted for the
mastectomy rate outcome measure. Finally, survival analyses were also conducted
as part of an exploratory analysis. RESULTS: Study participation was an
independent predictor of pCR in addition to commonly known predictors. Adjusted
odds ratio (OR) for trial participants versus non-participants was 1.53 (95% CI
1.03-2.28). Additionally, study participation improved the prediction of
mastectomy risk. The adjusted OR for trial participants versus non-participants
was 0.62 (95% CI 0.42-0.90). Subgroup-specific differences concerning the impact
of study participation could not be shown for either pCR or mastectomy rate.
Survival comparisons could not be conducted due to large differences in follow-up
data in patients participating in clinical trials versus those who did not
participate; however, pCR was a predictor of prognosis in both groups.
CONCLUSION: Patients taking part in neoadjuvant chemotherapy clinical trials have
a higher pCR rate and a lower mastectomy risk than patients not participating in
clinical trials for their cancer care. This finding is a supporting factor for
trial participation in neoadjuvant chemotherapy trials.
PMID- 29951971
TI - Higher-Order Asymptotics and Its Application to Testing the Equality of the
Examinee Ability Over Two Sets of Items.
AB - In educational and psychological measurement, researchers and/or practitioners
are often interested in examining whether the ability of an examinee is the same
over two sets of items. Such problems can arise in measurement of change,
detection of cheating on unproctored tests, erasure analysis, detection of item
preknowledge, etc. Traditional frequentist approaches that are used in such
problems include the Wald test, the likelihood ratio test, and the score test
(e.g., Fischer, Appl Psychol Meas 27:3-26, 2003; Finkelman, Weiss, & Kim-Kang,
Appl Psychol Meas 34:238-254, 2010; Glas & Dagohoy, Psychometrika 72:159-180,
2007; Guo & Drasgow, Int J Sel Assess 18:351-364, 2010; Klauer & Rettig, Br J
Math Stat Psychol 43:193-206, 1990; Sinharay, J Educ Behav Stat 42:46-68, 2017).
This paper shows that approaches based on higher-order asymptotics (e.g.,
Barndorff-Nielsen & Cox, Inference and asymptotics. Springer, London, 1994;
Ghosh, Higher order asymptotics. Institute of Mathematical Statistics, Hayward,
1994) can also be used to test for the equality of the examinee ability over two
sets of items. The modified signed likelihood ratio test (e.g., Barndorff
Nielsen, Biometrika 73:307-322, 1986) and the Lugannani-Rice approximation
(Lugannani & Rice, Adv Appl Prob 12:475-490, 1980), both of which are based on
higher-order asymptotics, are shown to provide some improvement over the
traditional frequentist approaches in three simulations. Two real data examples
are also provided.
PMID- 29951970
TI - Availability of prior mammograms affects incomplete report rates in mobile
screening mammography.
AB - PURPOSE: Mobile mammography can improve access to screening mammography in rural
areas and underserved populations. We evaluated the frequency of incomplete
reports in mobile mammography screening and the relationships between prior
mammograms and recall rates. METHODS: The frequency of incomplete mammogram
reports, the subgroups of those needing prior comparison mammograms, recalls for
additional imaging, and availability of prior mammograms of a mobile screening
mammography unit were compared with fixed site mammography from January 1, 2007
through December 31, 2009. All mobile unit mammograms were full field digital
mammography (FFDM). Differences between rates of recall, incomplete reports, and
availability of prior mammograms were calculated using the Chi-Square statistic.
RESULTS: Of 2640 mobile mammography cases, 21.9% (578) reports were incomplete,
versus 15.2% (7653) (p <= 0.001) of 50325 fixed site reports. Of incomplete
cases, recall for additional imaging occurred among 8.3% (218) of mobile
mammography reports versus 11.3% (5708) (p <= 0.001) of fixed site reports. Prior
mammograms were needed among 13.6% (360) of mobile mammography versus 3.9% (1945)
(p <= 0.001) of fixed site reports. Mobile mammography recall rate varied with
availability of prior mammograms: 16.0% (54) when no prior mammograms, 7.6% (127)
when prior mammograms were elsewhere but unavailable and 5.9% (37) when prior
FFDM were immediately available (p <= 0.001). CONCLUSIONS: Incomplete reports
were more frequent in mobile mammography than the fixed site. The availability of
prior comparison mammograms at time of interpretation decreased the rate of
incomplete mammogram reports. Recall rates were higher without prior comparison
mammograms and lowest when comparison FFDM mammograms were available.
PMID- 29951972
TI - A Network Intervention to Locate Newly HIV Infected Persons Within MSM Networks
in Chicago.
AB - Individuals with recent/acute HIV-infection have an increased likelihood of
disease transmission. To evaluate effectiveness of identifying recent infections,
we compared networks of recently and long-term HIV-infected individuals. The
Transmission Reduction Intervention Project included two separate arms of
recruitment, networks of recently HIV-infected individuals and networks of long
term HIV-infected individuals. Networks of each were recruited and tested for HIV
and syphilis infection. The per-seed yield ratios of recruitment were compared
between arms. Overall, 84 (41.6%) of 202 participants were identified as HIV
positive. HIV prevalence was higher (p < 0.001) among networks of recent seeds
(33/96, 34.4%) compared to long-term seeds (6/31, 19.4%). More individuals were
identified with active syphilis infection (p = 0.007) among networks of recent
seeds (15/96, 15.6%), compared to networks of long-term seeds (3/31, 9.7%).
Network-based recruitment of recently HIV-infected individuals was more effective
at identifying HIV and syphilis infection. Allocation of public health resources
may be improved by targeting interventions toward networks of recently HIV
infected individuals.
PMID- 29951974
TI - Reducing Risk Behavior with Family-Centered Prevention During the Young Adult
Years.
AB - Family-centered prevention is effective at reducing risk behavior throughout the
life span and promoting healthy development. Despite research that suggests
parents continue to play a significant role in the lives of their children during
emerging adulthood, very few studies have examined effective family-centered
strategies for preventing risk behavior in young adults. Typical prevention
efforts for this age group have focused on college students and substance use
prevention, with no integration of families or systems of support that may
sustain the effects of the intervention. In this study, we evaluated a version of
the Family Check-Up (FCU) that was adapted for young adults and their families,
the Young Adult Family Check-Up (YA-FCU). Families were randomly assigned to
receive the FCU or school as usual during the middle school years. Ten years
later, they were offered the YA-FCU, which was adapted for families of emerging
adult children. Intent-to-treat and complier average causal effect analyses were
used to examine change in young adult risk behavior approximately 1 year after
receiving the YA-FCU. Analyses indicated that random assignment alone or simple
engagement was not associated with reductions in young adult risk behavior.
However, dose-response analyses indicated that the more hours that youth and
families were engaged in the YA-FCU, the greater the reductions in young adult
risk behavior relative to those who did not engage or engaged very little in the
intervention, resulting in a medium effect size of the YA-FCU on risk behavior.
PMID- 29951973
TI - The availability of probiotics and donor human milk is associated with improved
survival in very preterm infants.
AB - BACKGROUND: To determine whether the introduction of pasteurized donor human milk
and probiotics for infants born < 32 weeks gestational age or < 1500 g
birthweight is associated with a reduction in mortality and the incidence of
necrotising enterocolitis (NEC) and sepsis. METHODS: We performed a retrospective
analysis of two cohorts: before and after the introduction of probiotics and
pasteurised donor human milk. Univariate analysis of primary and secondary
outcomes was performed; variables impacting outcomes were assessed using
multivariate logistic regression. RESULTS: There were 1791 infants: 1334 in the
pre-donor milk/probiotic cohort and 457 in the post-donor milk/probiotic cohort.
On univariate analysis, mortality (7.6 vs. 2.4%, P < 0.001) and incidence of
sepsis (6.2 vs. 3.5%, P = 0.028) were statistically significantly lower in the
post-donor milk/probiotic group. NEC (2.8 vs. 1.5%, P = 0.14) and non-NEC
associated gastrointestinal perforation (1.6 vs. 0.4%, P = 0.052) were lower in
the post-donor milk/probiotics cohort, but these were not statistically
significant. The difference in mortality remained statistically significant on
multivariate analysis in the post-donor milk/probiotic cohort compared to those
in the pre-donor milk/probiotic cohort (odds ratio 0.31, 95% confidence interval
0.16-0.61). The decrease in the incidence of NEC was consistent with previous
observational studies but the difference was not statistically significant.
CONCLUSION: The availability of probiotics and pasteurised donor human milk is
associated with a reduction in mortality in very preterm infants.
PMID- 29951976
TI - Frequency and type of incidentally detected radiodensities in the maxillary
sinus: a retrospective analysis using cone beam computed tomography (CBCT).
AB - OBJECTIVES: To evaluate the frequency, location, and characteristics of
radiodensities in the maxillary sinus using cone beam computed tomography (CBCT).
MATERIALS AND METHODS: All CBCT scans with a large field of view with both
maxillary sinuses entirely visible were initially screened. Patients were
included, if there was no suspicion of sinus pathology and no history of surgical
intervention/trauma in the sinus region. The location and shape of the
radiodensities were evaluated in axial, coronal, and sagittal CBCT views. The
findings were correlated with age, gender, condition of the sinus mucosa, and
status of the dentition. RESULTS: A total of 169 patients (338 maxillary sinuses)
were included. Radiodensities were found in 35 sinuses (10.4%) of 28 patients
(16.6%) with a mean age of 32.0 years. Most of the 35 affected sinuses had one
radiodensity (19/54.2%). The radiodensities were typically located at the sinus
floor (22/62.9%). Of the sinuses presenting with radiodensities, 17 (48.6%) were
exhibiting reactive changes of the Schneiderian membrane. The presence of
periodontal pathology was found to be associated with the presence of
radiodensities. Age and sinus pathology were influencing factors on the shape of
radiodensities, and the status of the dentition was an influencing factor on the
number of lesions. CONCLUSIONS: One-sixth of the patients analyzed had
incidentally diagnosed radiodensities in their maxillary sinuses. As almost 50%
of the sinuses with radiodensities exhibited a form of chronic rhinosinusitis,
the diagnosed ectopic calcifications may have formed as a result of mucosal
changes of inflammatory origin. The presence of periodontal pathology was
associated with a higher incidence of radiodensities. Nevertheless, this finding
has to be interpreted with some caution due to the limited sample size available.
CLINICAL RELEVANCE: Incidentally detected radiodensities in the maxillary sinus
are not an infrequent finding in CBCT scans of asymptomatic patients, and are
located typically on the sinus floor. Future studies are needed to assess the
clinical significance of these findings especially with regard to planned
surgical interventions in the posterior maxilla.
PMID- 29951975
TI - Effect of root canal sealers on the fracture resistance of endodontically treated
teeth: a systematic review of in vitro studies.
AB - OBJECTIVE: The purpose of this study was to systematically review and critically
analyze the published data of in vitro studies testing the effect of root canal
sealers on the fracture resistance of endodontically treated teeth. METHODS: A
comprehensive literature search was performed by using the Medline, Scopus, Web
of Science, Cochrane, and Open Grey databases. A hand search of the reference
lists of identified articles was also performed. Two reviewers critically
assessed the studies for eligibility against inclusion and exclusion criteria and
performed data extraction. Evaluation of the risk of bias of the studies was
performed. RESULTS: A total of 48 studies were assessed for eligibility. Of
these, 20 met the inclusion criteria and were included in the systematic review.
All studies had a medium or high risk of bias. Although the majority of the
studies reported that the use of root canal sealers increased the fracture
resistance of endodontically treated teeth, conflicting evidence was found for
the reinforcing effect of resin, glass ionomer, and calcium silicate-based
sealers while there was moderate evidence for zinc oxide eugenol-based sealers in
favor of no reinforcing effect. CONCLUSION: On the basis of available evidence,
the use of root canal sealer increases the fracture resistance of endodontically
treated teeth. However, included studies presented considerable risk of bias.
Regarding the comparisons among the sealers, no conclusions could be drawn for
the superiority of one sealer type to another. CLINICAL RELEVANCE: A considerable
heterogeneity was found in the methodologies of included studies. Therefore, this
review strongly suggests the development of standardized methods to test the
reinforcement effect of root canal filling materials in in vitro studies.
PMID- 29951977
TI - Cerebral Biochemical Effect of Pregabalin in Patients with Painful Diabetic
Neuropathy: A Randomized Controlled Trial.
AB - INTRODUCTION: With the development of new neuroimaging tools it has become
possible to assess neurochemical alterations in patients experiencing chronic
pain and to determine how these factors change during pharmacological treatment.
The goal of this study was to examine the exact neurochemical mechanism
underlying pregabalin treatment, utilizing magnetic resonance spectroscopy (1H
MRS), in a population of patients with painful diabetic polyneuropathy (PDN),
with the overall aim to ultimately objectify the clinical effect of pregabalin.
METHODS: A double blind, randomized, placebo-controlled study was conducted. A
total of 27 patients with PDN were enrolled in the study, of whom 13 received
placebo treatment (control group) and 14 received pregabalin (intervention
group). Pregabalin treatment consisted of stepwise dose escalation over the study
period from 75 mg daily ultimately to 600 mg daily. 1H-MRS was performed at 3T on
four regions of interest in the brain: the rostral anterior cingulate cortex
(rACC), left and right thalamus and prefrontal cortex. The absolute
concentrations of N-acetyl aspartate, glutamate, glutamine, gamma-amino-butyric
acid (GABA), glucose (Glc) and myo-inositol (mINS) were determined using LCModel.
RESULTS: The concentration of most neurometabolites in the placebo and pregabalin
group did not significantly differ over time, with only a small significant
difference in Glc level in the left thalamus (p = 0.049). Comparison of the
effects of the different doses revealed significant differences for mINS in the
rACC (baseline 2.42 +/- 1.21 vs. 450 mg 1.58 +/- 0.94; p = 0.022) and
dorsolateral prefrontal cortex (75 mg 2.38 +/- 0.89 vs. 450 mg 1.59 +/- 0.85; p =
0.042) and also for GABA in the rACC (75 mg 0.53 +/- 0.51 vs. 225 mg 0.28 +/-
0.19; p = 0.014). CONCLUSION: No differences were found in metabolite
concentrations between the placebo (control) and intervention groups, but some
differences, although small, were found between the different doses. TRIAL
REGISTRATION: This study is registered at ClinicalTrials.gov (NCT01180608).
FUNDING: Lyrica Independent Investigator Research Award (LIIRA) 2010 (Pfizer)
funded the study.
PMID- 29951978
TI - Contribution of BHG and PPHG to Overall Hyperglycemia in T2DM Patients Treated
with LM25 and LM50: Post Hoc Analysis of a Randomized Crossover Trial.
AB - INTRODUCTION: To investigate the relative contribution rates of basal
hyperglycemia (BHG) and postprandial hyperglycemia (PPHG) to overall
hyperglycemia in patients with type 2 diabetes mellitus (T2DM) treated with
insulin lispro mix 25 and 50 (LM25 and LM50) as evaluated by continuous glucose
monitoring (CGM). METHODS: Eighty-one T2DM patients treated with premixed human
insulin 70/30 (PHI70/30) were randomly divided into two groups and received a
crossover protocol. In the first 16-week stage, one group received LM25 twice
daily, the other group received LM50 twice daily. In the second 16-week stage,
the two groups exchanged therapeutic regimen. Glycosylated hemoglobin (HbA1c)
measurement and CGM were performed at enrollment and at the end of each treatment
stage. RESULTS: BHG's contribution rate increased with increasing HbA1c (from
34.5% to 60.8%). PPHG's contribution rates in the LM50 regimen were significantly
lower than those in LM25 and PHI70/30 regimens at HbA1c levels < 7.5%. Compared
with LM50, LM25 shows a significant difference in reducing HbA1c in the subgroup
with baseline HbA1c >= 8.5% (DeltaHbA1c LM25 vs. LM50 - 0.6 +/- 0.1% vs. 0.3 +/-
0.1%, p < 0.05). CONCLUSIONS: For T2DM patients treated with premixed insulin
analogues, postprandial hyperglycemia played a major role in the subgroup of
patients with HbA1c < 8.5%, while fasting hyperglycemia became the major
contributor to overall hyperglycemia in the subgroup of patients with HbA1c >=
8.5%. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier ChiCTR-TTRCC
12002516. FUNDING: Lilly Suzhou Pharmaceutical Co., Ltd. (Shanghai Branch, China)
and National Key Program of Clinical Science of China (WBYZ2011-873).
PMID- 29951979
TI - Repeated Failure in Reward Pursuit Alters Innate Drosophila Larval Behaviors.
AB - Animals always seek rewards and the related neural basis has been well studied.
However, what happens when animals fail to get a reward is largely unknown,
although this is commonly seen in behaviors such as predation. Here, we set up a
behavioral model of repeated failure in reward pursuit (RFRP) in Drosophila
larvae. In this model, the larvae were repeatedly prevented from reaching
attractants such as yeast and butyl acetate, before finally abandoning further
attempts. After giving up, they usually showed a decreased locomotor speed and
impaired performance in light avoidance and sugar preference, which were named as
phenotypes of RFRP states. In larvae that had developed RFRP phenotypes, the
octopamine concentration was greatly elevated, while tbetah mutants devoid of
octopamine were less likely to develop RFRP phenotypes, and octopamine feeding
efficiently restored such defects. By down-regulating tbetah in different groups
of neurons and imaging neuronal activity, neurons that regulated the development
of RFRP states and the behavioral exhibition of RFRP phenotypes were mapped to a
small subgroup of non-glutamatergic and glutamatergic octopaminergic neurons in
the central larval brain. Our results establish a model for investigating the
effect of depriving an expected reward in Drosophila and provide a simplified
framework for the associated neural basis.
PMID- 29951980
TI - Preventive role of ramelteon and suvorexant for postoperative delirium after
pharyngolaryngectomy with esophagectomy.
PMID- 29951981
TI - Immediate extubation after esophagectomy with three-field lymphadenectomy enables
early ambulation in patients with thoracic esophageal cancer.
AB - BACKGROUND: We retrospectively compared the effects of immediate extubation (IE)
in the operating room with those of overnight mechanical ventilation (MV) after
radical transthoracic esophagectomy with 3-field lymphadenectomy in patients with
thoracic esophageal cancer. METHODS: A total of 96 patients were evaluated. 48
patients were extubated in the operating room after surgery (IE group). The other
48 patients were extubated on the following morning (MV group). The propensity
score-matching method was used to assemble a well-balanced cohort. Clinical and
postoperative outcomes were investigated in each group. We also compared
postoperative laboratory parameters between groups. RESULTS: The rate of
ambulation on postoperative day (POD) 1 was significantly higher in the IE group
compared with that in the MV group (50 vs 19%, respectively, p = 0.003).
Moreover, the rate of catecholamine use in the ICU was significantly lower in the
IE group compared with that in the MV group (15 vs 65%, respectively, p < 0.001).
With regard to postoperative respiratory management, there were no significant
differences between groups. The length of ICU stay after esophagectomy was
significantly shorter in the IE group compared with that in the MV group (p =
0.01), whereas the length of postoperative hospital stay was similar between
groups (p = 0.265). There were also no significant differences in the incidence
of postoperative complications. CONCLUSIONS: IE in the operating room is not only
safe and feasible, even after transthoracic esophagectomy with radical 3-field
lymphadenectomy, but also contributes to decrease in catecholamine use, to
increase in ambulation on POD 1 and to shorten the ICU stay.
PMID- 29951982
TI - Mediastinoscopic view of the bronchial arteries in a series of surgical cases
evaluated with three-dimensional computed tomography.
AB - BACKGROUND: We have routinely performed three-dimensional computed tomography (3
D CT) prior to video-assisted transmediastinal esophagectomy to evaluate the
small arteries in the mediastinal operative field. This evaluation would be
helpful in performing mediastinoscopic esophagectomy. METHODS: Thirty-one
patients who underwent transmediastinal esophagectomy with preoperative
evaluations by 3-D CT were the study subject. The bronchial arteries depicted by
the 3-D CT were classified by their origin and laterality. In 18 of the 31 cases,
the surgical video was available and the identification rate in the video was
reviewed for each of the categorized bronchial arteries. RESULTS: The detection
rates of each classified artery were as follows (abbreviations, detection rate);
the intercostal-bronchial trunk (IBT, 22/31), the direct left bronchial artery
(LBA, 17/31), the common trunk of bronchial arteries (CTB, 7/31), the direct
right bronchial artery (RBA, 2/31), and the ectopic arteries (16/31). The ectopic
arteries arose from the aortic arch (11 cases), the right subclavian artery (6
cases) or the left subclavian artery (1 case). The identification rates of IBT,
LBA, CTB, RBA and any of the ectopic arteries in the video review were 12/13,
4/8, 3/4, 1/1 and 2/10, respectively. CONCLUSIONS: Preoperative 3-D CT was a
highly sensitive evaluation for the bronchial arteries encountered during
transmediastinal esophagectomy. Orthotopic arteries except for LBA were
frequently identified at the predicted sites. Although RBA and CTB were present
infrequently, they often flowed into regional nodes at the bilateral bronchi or
the tracheal bifurcation and, therefore, should be preoperatively evaluated.
PMID- 29951983
TI - The effect of platelet-rich plasma on motility changes in experimental caustic
esophageal burn.
AB - BACKGROUND: Besides stricture formation, diminished esophageal motility after
caustic esophageal burns also plays a role in the deterioration of the clinical
course. In this study, we aimed to investigate the effect of caustic burn on the
esophageal contractions and the effect of platelet-rich plasma (PRP) on these
changes. METHODS: Twenty-one Wistar albino rats were divided into three groups
[Sham operation (n = 8), caustic esophageal burn with NaOH (n = 6), PRP treatment
after caustic burn (n = 7)]. After 3 weeks, esophagectomy was performed and
contractions and EFS responses were evaluated in the organ bath. RESULTS: KCl-
and acetylcholine-induced responses were reduced in the Burn group, but increased
in Sham and PRP groups (p < 0.05). EFS responses were higher in Burn group
compared to the other groups. Response with L-arginine was increased in Burn
group, but decreased in PRP group. There was more decrease in the contraction in
Sham and PRP groups compared to the Burn group after SNP (sodium nitroprusside)
incubation (p < 0.05). L-NAME (Nomega-Nitro-L-arginine methyl ester) did not
change the EFS responses in the Burn group, but EFS responses were decreased
significantly in Sham and PRP groups (p < 0.05). EFS responses were decreased in
all groups, but more in the Sham and PRP groups after Y-27632 (Rho-kinase
inhibitor) incubation (p < 0.05). CONCLUSIONS: For the first time, we
demonstrated that both cholinergic and non-adrenergic non-cholinergic mechanisms
are responsible for the altered motility in corrosive esophageal injury. Our
results suggest that PRP treatment may be helpful in regulating the esophageal
motility and decreasing altered contractions in corrosive burns. This effect may
also contribute to the reduction of stricture formation, especially by reducing
inappropriate contractions of the esophageal wall during the post-burn healing
phase.
PMID- 29951984
TI - Impact of change in serum albumin level during and after chemoradiotherapy in
patients with locally advanced esophageal cancer.
AB - BACKGROUND: In patients with locally advanced esophageal cancer treated by
concurrent chemoradiotherapy (CCRT), baseline malnutrition and its progression
have been shown to be associated with a poor outcome. We conducted this study to
determine the variation in four blood test parameters including serum albumin
level (ALB), creatinine (Cre), hemoglobin (Hb) and platelet (Plt) during CCRT for
stage III esophageal cancer patients and its effect on patients' outcome.
METHODS: One hundred eighty-three patients diagnosed with stage III esophageal
cancer were retrospectively investigated. In addition to known prognostic
factors, baseline level of the four blood test parameters and their variation at
day 105 (DeltaALB, DeltaCre, DeltaHb and DeltaPlt, respectively) were analyzed.
RESULTS: The median observation period for patients who survived was 57.2 months,
and the 5-year overall survival rate was 35.6% (95% CI 34.2-36.9%). In
multivariate analyses, baseline ALB (>= 3.6 g/dL), higher DeltaALB (>= + 0.3
g/dL) were independent predictors for overall survival (p = 0.001 and < 0.001,
respectively), in addition to other clinical factors including T stage and
overall treatment time (OTT). For disease-free survival, DeltaALB was only a
predictor in hematological parameters (p = 0.001) in addition to T stage and OTT.
No hematological and clinical parameters had significant correlation with local
control in multivariate analysis. Furthermore, DeltaALB showed significant
correlation with OS and DFS in log-rank test (p = 0.002 and 0.002, respectively).
CONCLUSIONS: Our results suggest improvement in ALB after treatment might be a
favorable prognostic factor in esophageal cancer patients treated by CCRT.
PMID- 29951985
TI - Clinical characteristics and management of gastric tube cancer after
esophagectomy.
AB - BACKGROUND: Gastric cancer is the second most common malignancy, overlapping with
thoracic esophageal cancer (TEC). Among them, metachronous gastric tube cancers
after TEC surgery have been increasing. The aims of this study were to examine
the clinicopathological factors and treatment outcomes of gastric tube cancer
(GTC) after TEC surgery. METHODS: Thirty-three GTCs in 30 cases after TEC treated
between 1997 and 2016 were investigated retrospectively. RESULTS: Most cases were
males. The median interval from TEC surgery to GTC occurrence was 57 (6.5-107.5)
months. Almost 2/3 lesions occurred in the lower third of the gastric tube
(21/33); 29 lesions (in 26 cases) were superficial cancers, and 4 lesions were
advanced cancers. Twenty-two lesions of superficial cancer were differentiated
type, and the remaining seven lesions were undifferentiated type. Treatment for
superficial cancer had previously been performed with partial gastric tube
resection (10 lesions), and the number of cases undergoing endoscopic submucosal
dissection (ESD) had increased recently (19 lesions). Most cases with superficial
cancer survived without relapse. Four lesions of advanced cancer were found after
a relatively long interval following TEC surgery. Most lesions of advanced cancer
were scirrhous, undifferentiated type, and they died due to GTC. CONCLUSION: GTCs
may occur late in the postoperative course following TEC surgery. If they are
discovered at an early stage, these lesions can be cured with ESD. Long-term
periodic endoscopic examinations after TEC surgery are important.
PMID- 29951986
TI - Reply to: Preventive role of ramelteon and suvorexant for postoperative delirium
after pharyngolaryngectomy with esophagectomy.
PMID- 29951987
TI - Recent progress in perioperative management of patients undergoing esophagectomy
for esophageal cancer.
AB - Esophagectomy remains the mainstay of curative intent treatment for esophageal
cancer. Oncologic esophagectomy is a highly invasive surgery and both morbidity
and mortality rates still remain high. Recently, it has been revealed that
multidisciplinary perioperative management can decrease the postoperative
complications after esophagectomy. In this review, we summarized the recent
progress in each component of multidisciplinary perioperative care bundle,
including oral hygiene, cessation of smoking and alcohol, respiratory training,
measurement of physical fitness, swallowing evaluation and rehabilitation,
nutritional support, pain control and management of delirium. The accumulation of
evidence and the popularization of knowledge will increase safety of
esophagectomy and thus improve the outcome of patients with esophageal cancer.
PMID- 29951988
TI - FZL is primarily localized to the inner chloroplast membrane however influences
thylakoid maintenance.
AB - KEY MESSAGE: FZL is primarily localized to the chloroplast inner envelope and not
to the thylakoids, but nevertheless affects the maintenance of thylakoid
membranes and photosynthetic protein complexes. The fuzzy-onion-like protein
(FZL) is a membrane-bound dynamin-like GTPase located in the chloroplast. We have
investigated the chloroplast sub-localization of the endogenous FZL protein and
found it to be primarily localized to the inner envelope. Moreover, we observed
that mature leaves of fzl mutants start to turn pale, especially in the midvein
area of the leaves, 11 days after germination. We therefore assessed their
photosynthetic performance as well as the accumulation of thylakoid membrane
proteins and complexes after the initial appearance of the phenotype.
Interestingly, we could observe a significant decrease in amounts of the
cytochrome b6f complex in 20-day-old mutants, which was also reflected in an
impaired electron transport rate as well as a more oxidized P700 redox state.
Analysis of differences in transcriptome datasets obtained before and after onset
of the phenotype, revealed large-scale changes in gene expression after the
phenotype became visible. In summary, we propose that FZL, despite its
localization in the inner chloroplast envelope has an important role in thylakoid
maintenance in mature and aging leaves.
PMID- 29951989
TI - Stress-induced antioxidant defense and protein chaperone response in the freeze
tolerant wood frog Rana sylvatica.
AB - Freeze tolerance is an adaptive response utilized by the wood frog Rana sylvatica
to endure the sub-zero temperatures of winter. Survival of whole body freezing
requires wood frogs to trigger cryoprotective mechanisms to deal with potential
injuries associated with conversion of 65-70% of total body water into ice,
including multiple consequences of ice formation such as cessation of blood flow
and cell dehydration caused by water loss into ice masses. To understand how wood
frogs defend against these stressors, we measured the expression of proteins
known to be involved in the antioxidant defense and protein chaperone stress
responses in brain and heart of wood frogs comparing freezing, anoxia, and
dehydration stress. Our results showed that most stress proteins were regulated
in a tissue- and stress-specific manner. Notably, protein levels of the cytosolic
superoxide dismutase (SOD1) were upregulated by 1.37 +/- 0.11-fold in frozen
brain, whereas the mitochondrial SOD2 isoform rose by 1.38 +/- 0.37-fold in the
heart during freezing. Catalase protein levels were upregulated by 3.01 +/- 0.47
fold in the brain under anoxia stress, but remained unchanged in the heart.
Similar context-specific regulatory patterns were also observed for the heat
shock protein (Hsp) molecular chaperones. Hsp27 protein was down-regulated in the
brain across the three stress conditions, whereas the mitochondrial Hsp60 was
upregulated in anoxic brain by 1.73 +/- 0.38-fold and by 2.13 +/- 0.57-fold in
the frozen heart. Overall, our study provides a snapshot of the regulatory
expression of stress proteins in wood frogs under harsh environment conditions
and shows that they are controlled in a tissue- and stress-specific manner.
PMID- 29951990
TI - The three faces of pericytes.
PMID- 29951991
TI - Investigation on characteristics of 3D printing using Nostoc sphaeroides biomass.
AB - BACKGROUND: Gel-like constructs can be produced using an extrusion-based 3D food
printing (3D-FP) technique. Nostoc sphaeroides biomass is a natural gel material.
Considering its good nutrition and rheological properties, these algae were
chosen in this study as supply material (ink) for 3D-FP. With this gel material,
the extrusion-based 3D printing system was set as a model, and the printing
behavior was investigated. Furthermore, the 3D-FP mechanisms were explained
through low-field nuclear magnetic resonance and rheological measurements.
RESULTS: Results indicated that although fresh biomass gel was printable, non
uniformity and instability occurred during printing. Blanched inks showed non
smooth printing behavior, which was associated with a decrease in elasticity and
viscosity. Printability was improved by increasing the rehydration time to 24 h
when rehydrated powder was used. Increasing the rehydration time increased the
water-binding degree. Pre-gelatinized potato starch was added to the mixture at
ratios ranging from 1 to 100 g kg-1 . The best printing outcome was observed at
40 g kg-1 potato starch. CONCLUSION: We emphasize that elasticity and viscosity
balance is an essential parameter to achieve printability. The strategies adopted
in this work provide new insights into the development of personalized food
regarding texture and nutritional additive content. (c) 2018 Society of Chemical
Industry.
PMID- 29951992
TI - Effects of three different stunning/slaughtering methods on physical, chemical,
and sensory changes in rainbow trout (Oncorhynchus mykiss).
AB - BACKGROUND: Electrical stunning (E) and asphyxia in the air (A) are two common
stunning/killing methods for fish. However, they can stress the fish and affect
flesh quality, so an alternative should be found. The present study aimed to
evaluate the effects of carbon monoxide asphyxia (CO) compared to E and A on the
evolution of post rigor mortis changes in rainbow trout (Oncorhynchus mykiss)
fillets related to chemical, textural, and sensorial properties during storage
time. RESULTS: Fish fillets from the E group showed a higher pH (P < 0.05) than
the A ones, both at time of rigor resolution (TRR 0) and from TRR 4 until TRR 7
(7 days after rigor resolution, which corresponded to 10 days post mortem), with
the CO group being always intermediate. The CO treatment ensured that the fillets
showed the lowest yellowness index (b*), even if only at TRR 2 and TRR 5. Lipid
oxidation and texture profile analyses were unaffected. Sensory analysis revealed
that the CO fillets had the lowest odor intensity and the highest juiciness
scores (P < 0.05). The sensory descriptors resulted the most discriminant
variables of the fillets obtained from the differently stunned animals, as
resulted by the canonical discriminant analysis. CONCLUSION: The carbon monoxide
stunning/slaughtering method could be applied to rainbow trout without
detrimental effects on physical, chemical, or sensory characteristics of the fish
flesh. (c) 2018 Society of Chemical Industry.
PMID- 29951993
TI - Clinical manifestations, risk factors and quality of life in patients with pitted
keratolysis: a cross-sectional study in cadets.
PMID- 29951994
TI - A Novel Method to Estimate Long-Term Chronological Changes From Fragmented
Observations in Disease Progression.
AB - Clinical observations of patients with chronic diseases are often restricted in
terms of duration. Therefore, obtaining a quantitative and comprehensive
understanding of the chronology of chronic diseases is challenging, because of
the inability to precisely estimate the patient's disease stage at the time point
of observation. We developed a novel method to reconstitute long-term disease
progression from temporally fragmented data by extending the nonlinear mixed
effects model to incorporate the estimation of "disease time" of each subject.
Application of this method to sporadic Alzheimer's disease successfully depicted
disease progression over 20 years. The covariate analysis revealed earlier onset
of amyloid-beta accumulation in male and female apolipoprotein E epsilon4
homozygotes, whereas disease progression was remarkably slower in female epsilon3
homozygotes compared with female epsilon4 carriers and males. Simulation of a
clinical trial suggests patient recruitment using the information of precise
disease time of each patient will decrease the sample size required for clinical
trials.
PMID- 29951995
TI - Dose rates of electron beam and gamma ray irradiation affect microbial
decontamination and quality changes in dried red pepper (Capsicum annuum L.)
powder.
AB - BACKGROUND: Due to differences in radiation sources (electron beam from electron
accelerator, gamma ray from 60 Co radionuclide) and energy delivery time (dose
rate, kGy/time), the effects on foods are expected to be different with regard to
chemical quality change and microbial decontamination. To better understand this
impact, effects of variable dose rates of electron beam (EB, kGy s-1 ) and gamma
rays (GR, kGy h-1 ) on microbial reduction, capsanthin content, and color
parameters of red pepper (Capsicum annuum L.) powders (RPP) were determined. RPP
samples were irradiated with 3 kGy absorbed dose, at variable dose rates of 1 and
5 kGy s-1 of EB (10 MeV/10 kW), and 1.8 and 9 kGy h-1 of GR (60 Co). RESULTS:
Aerobic plate counts (APC) as well as yeast and mold counts of non-irradiated
samples were 7.12 log CFU g-1 and 6.62 log CFU g-1 , respectively. EB and GR
reduced these by 2-3 log CFU g-1 . A lower dose rate (1 kGy s-1 ) of EB was more
effective for microbial reduction than a higher dose rate (5 kGy s-1 ). In
contrast, a higher dose rate (9 kGy h-1 ) of GR efficiently decreased APC
compared to a lower dose rate (1.8 kGy h-1 ). Higher EB and GR dose rates
significantly decreased the capsanthin content and Hunter's red color (a* value).
CONCLUSION: Low EB (kGy s-1 ) and high GR (kGy h-1 ) dose rates are recommended
for microbiological safety of RPP with negligible changes in color attributes
visible to the human eye, in contrast to the measured values. Thus the study
demonstrates that the influence of absorbed dose is dependent on the applied dose
rates. (c) 2018 Society of Chemical Industry.
PMID- 29951996
TI - Regional Practice Patterns and Racial/Ethnic Differences in Intensity of End-of
Life Care.
AB - OBJECTIVE: To examine whether regional practice patterns impact racial/ethnic
differences in intensity of end-of-life care for cancer decedents. DATA SOURCES:
The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database.
STUDY DESIGN: We classified hospital referral regions (HRRs) based on mean 6
month end-of-life care expenditures, which represented regional practice
patterns. Using hierarchical generalized linear models, we examined racial/ethnic
differences in the intensity of end-of-life care across levels of HRR
expenditures. PRINCIPAL FINDINGS: There was greater variation in intensity of end
of-life care among Hispanics, Asians, and whites in high-expenditure HRRs than in
low-expenditure HRRs. CONCLUSIONS: Local practice patterns may influence
racial/ethnic differences in end-of-life care.
PMID- 29951997
TI - Observations of follicle cell processes in a holocephalan.
AB - The presence of follicular cellular processes (FCP) that cross the zona
pellucida, has been recorded in the ovarian follicles of Callorhinchus
callorhynchus. This constitutes the first report describing the presence of these
structures in a species of the Holocephali. Considering that FCPs have only
previously been reported in the Selachii, these findings suggest that FCPs could
have been lost by the Batoidea after their divergence, around 280 M B.P.
PMID- 29951998
TI - Novel mutation in MBTPS2 causes keratosis follicularis spinulosa decalvans in a
large Chinese family.
PMID- 29951999
TI - Review on plant protein-polysaccharide complex coacervation, and the
functionality and applicability of formed complexes.
AB - Controlling the interactions between plant proteins and polysaccharides can lead
to the development of novel electrostatic complexed structures that can give
unique functionality. This in turn can broaden the diversity of applications that
they may be suitable for. Overwhelmingly in the literature, work and reviews
relating to coacervation have involved the use of animal proteins. However, with
the increasing demand for plant-based protein alternatives by industry and
consumers, a greater understanding of how they interact with polysaccharides is
essential to control structure, functionality and applicability. This review
discusses the factors governing the nature of protein-polysaccharide
interactions, their functional attributes and industrial applications, with
special attention given to plant proteins. (c) 2018 Society of Chemical Industry.
PMID- 29952000
TI - Cholinesterase inhibitors for the treatment of delirium in non-ICU settings.
AB - BACKGROUND: Delirium is a common clinical syndrome defined as alterations in
attention with an additional disturbance in cognition or perception, which
develop over a short period of time and tend to fluctuate during the course of
the episode. Delirium is commonly treated in hospitals or community settings and
is often associated with multiple adverse outcomes such as increased cost,
morbidity, and even mortality. The first-line intervention involves a
multicomponent non-pharmacological approach that includes ensuring effective
communication and reorientation in addition to providing reassurance or a
suitable care environment. There are currently no drugs approved specifically for
the treatment of delirium. Clinically, however, various medications are employed
to provide symptomatic relief, such as antipsychotic medications and
cholinesterase inhibitors, among others. OBJECTIVES: To evaluate the
effectiveness and safety of cholinesterase inhibitors for treating people with
established delirium in a non-intensive care unit (ICU) setting. SEARCH METHODS:
We searched ALOIS, which is the Cochrane Dementia and Cognitive Improvement
Group's Specialised Register, on 26 October 2017. We also cross-checked the
reference lists of included studies to identify any potentially eligible trials.
SELECTION CRITERIA: We included randomised controlled trials, published or
unpublished, reported in English or Chinese, which compared cholinesterase
inhibitors to placebo or other drugs intended to treat people with established
delirium in a non-ICU setting. DATA COLLECTION AND ANALYSIS: We used the standard
methodological procedures expected by Cochrane. The primary outcomes were
duration of delirium, severity of delirium, and adverse events. The secondary
outcomes were use of rescue medications, persistent cognitive impairment, length
of hospitalisation, institutionalisation, mortality, cost of intervention,
leaving the study early, and quality of life. For dichotomous outcomes, we
calculated the risk ratio (RR) with 95% confidence intervals (CIs); for
continuous outcomes we calculated the mean difference (MD) with 95% CIs. We
assessed the quality of evidence using GRADE to generate a 'Summary of findings'
table. MAIN RESULTS: We included one study involving 15 participants from the UK.
The included participants were diagnosed with delirium based on the Confusion
Assessment Method (CAM) criteria. Eight males and seven females were included,
with a mean age of 82.5 years. Seven of the 15 participants had comorbid dementia
at baseline. The risk of bias was low in all domains.The study compared
rivastigmine with placebo. We did not find any clear differences between the two
groups in terms of duration of delirium (MD -3.6, 95% CI -15.6 to 8.4), adverse
events (nausea, RR 0.30, 95% CI 0.01 to 6.29), use of rescue medications (RR
0.13, 95% CI 0.01 to 2.1), mortality (RR 0.10, 95% CI 0.01 to 1.56), and leaving
the study early (RR 0.88, 95% CI 0.07 to 11.54). Evidence was not available
regarding the severity of delirium, persistent cognitive impairment, length of
hospitalisation, cost of intervention, or other predefined secondary outcomes.The
quality of evidence is low due to the very small sample size. AUTHORS'
CONCLUSIONS: There is insufficient evidence to support or refute the use of
cholinesterase inhibitors for the treatment of delirium in non-ICU settings. No
clear benefits or harms associated with cholinesterase inhibitors were observed
when compared with placebo due to the lack of data. More trials are required.
PMID- 29952001
TI - Comparison between Atlantic salmon Salmo salar post-smolts reared in open sea
cages and in the Preline raceway semi-closed containment aquaculture system.
AB - The use of closed containment (CCS) or semi-closed containment systems (S-CCS)
for Atlantic salmon Salmo salar aquaculture is under evaluation in Norway. One
such system is the Preline S-CCS, a floating raceway system that pumps water from
35 m depth creating a constant current through the system. Exposing fish to
moderate water currents is considered aerobic exercise and it is often perceived
as positive for fish welfare, growth, food utilization, muscle development and
cardiac health. The present study compared fish reared in the Preline S-CCS and
in a reference open pen. Samples were taken in fresh water before being
transferred to the seawater systems and after 1, 2 and 4 months in seawater and
analysed for growth, mortality, muscle development and plasma insulin-like growth
factor I (IGF-I) levels. Moreover, gene transcription were determined in the
skeletal muscle [igf-I, insulin-like growth factor 1 receptor a (igf1ra) and
insulin-like growth factor 1 binding protein 1a (igf1bp1a)] and cardiac
transcription factors [myocyte-specific enhancer factor 2C (mef2c), gata4 and
vascular endothelial growth factor (vegf)]. While the results suggest that post
smolts in Preline S-CCS were smaller than reference fish, fish from Preline S-CCS
have less accumulated mortality at the end of the experiment and showed 2.44
times more small muscle fibres than the reference group fish after 4 months in
seawater. These results confirmed what was previously observed in the second
generation of Preline. Similar levels of big muscle fibres between Preline S-CCS
and reference suggest a similar hypertrophy of muscle fibres even with lower IGF
I expression in the Preline S-CCS. Cardiac gene transcription suggests cardiac
hypertrophy was observed after 4 months in seawater in the Preline S-CCS group.
Altogether, Preline S-CCS is a promising technology able to produce more robust
S. salar with a faster growth and lower mortality in the subsequent standard open
cage system growth period.
PMID- 29952002
TI - Role of immune cells in hypertension.
AB - Inflammatory processes have been shown to play an important role in the
mechanisms involved in the pathogenesis of hypertension. Innate and adaptive
immune responses participate in BP elevation and end-organ damage. Here, we
discuss recent studies focusing on novel inflammatory and immune mechanisms that
play roles in BP elevation. Different subpopulations of cells involved in innate
and adaptive immune responses, such as dendritic cells, monocytes/macrophages and
NK cells, on the one hand, and B and T lymphocytes, on the other, contribute to
the vascular and kidney injury in hypertension. Unconventional innate-like T
cells such as gammadelta T cells also participate in hypertensive mechanisms by
priming both innate and adaptive immune cells, contributing to trigger vascular
inflammation and BP elevation. These cells exert their effects in part via
production of various cytokines including pro-inflammatory IFN-gamma and IL-17
and anti-inflammatory IL-10. The present review summarizes some of these immune
mechanisms that participate in the pathophysiology of hypertension.
PMID- 29952004
TI - Randomized Phase I Healthy Volunteer Study of UTTR1147A (IL-22Fc): A Potential
Therapy for Epithelial Injury.
AB - Most treatments for epithelial injury target hematopoietic mechanisms, possibly
causing immunosuppression. Interleukin (IL)-22 promotes tissue regeneration,
acting directly on epithelial cells. UTTR1147A, a human IL-22Fc (immunoglobulin G
(IgG)4) fusion protein, activates IL-22 signaling. This phase I placebo
controlled trial of single, ascending, i.v. (1-120 MUg/kg) and s.c (3-120 MUg/kg)
doses of UTTR1147A analyzed its effects on safety, tolerability,
pharmacokinetics, and pharmacodynamic biomarkers in healthy volunteers. Most
adverse events (AEs) were mild or moderate. The maximum tolerated i.v. dose in
healthy volunteers was 90 MUg/kg. Predominant AEs were dose-dependent reversible
skin effects consistent with IL-22 pharmacology. UTTR1147A exposure increased
approximately dose-proportionally, with a half-life of ~1 week. IL-22 biomarkers
(regenerating islet protein 3A (REG3A), serum amyloid A (SAA), and C-reactive
protein (CRP)) increased dose-dependently. Neither inflammatory symptoms and
signs nor cytokines increased with CRP elevations. UTTR1147A demonstrated
acceptable safety, pharmacokinetics, and IL-22R engagement, supporting further
clinical development.
PMID- 29952003
TI - Geminin ablation in vivo enhances tumorigenesis through increased genomic
instability.
AB - Geminin, a DNA replication licensing inhibitor, ensures faithful DNA replication
in vertebrates. Several studies have shown that geminin depletion in vitro
results in rereplication and DNA damage, whereas increased expression of geminin
has been observed in human cancers. However, conditional inactivation of geminin
during embryogenesis has not revealed any detectable DNA replication defects. In
order to examine its role in vivo, we conditionally inactivated geminin in the
murine colon and lung, and assessed chemically induced carcinogenesis. We show
here that mice lacking geminin develop a significantly higher number of tumors
and bear a larger tumor burden than sham-treated controls in urethane-induced
lung and azoxymethane/dextran sodium sulfate-induced colon carcinogenesis.
Survival is also significantly reduced in mice lacking geminin during lung
carcinogenesis. A significant increase in the total number and grade of lesions
(hyperplasias, adenomas, and carcinomas) was also confirmed by hematoxylin and
eosin staining. Moreover, increased genomic aberrations, identified by increased
ATR and gammaH2AX expression, was detected with immunohistochemistry analysis. In
addition, we analyzed geminin expression in human colon cancer, and found
increased expression, as well as a positive correlation with ATM/ATR levels and a
non-monotonic association with gammaH2AX. Taken together, our data demonstrate
that geminin acts as a tumor suppressor by safeguarding genome stability, whereas
its overexpression is also associated with genomic instability. Copyright (c)
2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 29952005
TI - Camu-camu (Myrciaria dubia) from commercial cultivation has higher levels of
bioactive compounds than native cultivation (Amazon Forest) and presents
antimutagenic effects in vivo.
AB - BACKGROUND: Camu-camu (Myrciaria dubia) is a typical Amazonian fruit and has high
antioxidant capacity due to its high levels of vitamin C and phenolic compounds.
This study aimed to determine the phytochemicals, antioxidant capacity and
antimutagenic effects of camu-camu fruits with different maturity stages grown in
dry (commercial cultivation) or flooded environments (native cultivation,
Amazon). RESULTS: Total polyphenols, ascorbic acid and in vitro antioxidant
capacity levels were higher in ripe fruits grown in a commercial cultivation. The
extracts from ripe camu-camu grown in a commercial cultivation exerted
antioxidant effects and high percentage of protection against doxorubicin and 1,2
dimethylhydrazine in all tested systems (liver, bone marrow and gut), for three
camu-camu extract concentrations (17, 85 and 170 mg kg-1 body weight), as
follows: bone marrow minocronucleus (37.91%, 41.75%, 43.95%); micronucleus gut
test (61.01%, 64.40%, 50.28%); apoptosis index (60.26%, 62.44%, 58.22%); comet
assay through the tail moment (71.64%, 72.31%, 70.70%), percent DNA in the tail
(64.54%, 68.75%, 76.79%) and tail intensity (76.43%, 81.02%, 68.33%). CONCLUSION:
The results of this study contribute to increasing the production of camu-camu
fruits grown in dry environments and their use as a health-promoting food. (c)
2018 Society of Chemical Industry.
PMID- 29952006
TI - Plasminogen gene mutation with normal C1 inhibitor hereditary angioedema: Three
additional French families.
PMID- 29952008
TI - Abstracts of the Endocrine Society of Australia's Annual Scientific Meeting 2017.
PMID- 29952007
TI - A high-performance liquid chromatography-tandem mass spectrometry method for
simultaneous determination of imigliptin, its five metabolites and alogliptin in
human plasma and urine and its application to a multiple-dose pharmacokinetic
study.
AB - Imigliptin is a novel DPP-4 inhibitor, designed to treat type 2 diabetes mellitus
(T2DM). A selective and sensitive method was developed using high performance
liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) to
simultaneously quantify imigliptin, its five metabolites, and alogliptin in human
plasma and urine. Solid-phase extraction (SPE) and direct dilution were used to
extract imigliptin, its five metabolites, alogliptin from plasma and urine,
respectively. The extracts were injected onto a SymmetryShield RP8 column with a
gradient elution of methanol and water containing 10 mM ammonium formate (pH =
7). Ionization of all analytes was performed using an electrospray ionization
(ESI) source in positive mode and detection was carried out with multiple
reaction monitoring (MRM) mode. The results revealed that the method had
excellent selectivity and linearity. Inter- and intra-batch precisions of all
analytes were less than 15% and the accuracies were within 85%-115% for both
plasma and urine. The sensitivity, matrix effect, extraction recovery, linearity,
and stabilities were validated for all analytes in human plasma and urine. In
conclusion, the validation results showed that this method was robust, specific,
and sensitive and it can successfully applied to a pharmacokinetic study of
Chinese T2DM subjects after oral dose of imigliptin and alogliptin.
PMID- 29952009
TI - The 2017 Malcolm Ferguson-Smith Young Investigator Award.
PMID- 29952010
TI - Short-term high temperature treatment reduces viability and inhibits respiration
and DNA repair enzymes in Araucaria angustifolia cells.
AB - We evaluated the effect of global warming on Araucaria angustifolia (Bert.) O.
Kuntze, a critically endangered native tree of Southern Brazil, by studying the
effects of short-term high temperature treatment on cell viability, respiration
and DNA repair of embryogenic cells. Compared with control cells grown at 25
degrees C, cell viability was reduced by 40% after incubation at 30 and 37
degrees C for 24 and 6 h, respectively, while 2 h at 40 and 42 degrees C killed
95% of the cells. Cell respiration was unaffected at 30-37 degrees C, but
dramatically reduced after 2 h at 42 degrees C. The in vitro activity of enzymes
of the base excision repair (BER) pathway was determined. Apurinic/apyrimidine
endonuclease, measured in extracts from cells incubated for 2 h at 42 degrees C,
was completely inactivated while lower temperatures had no effect. The activities
of three enzymes of the mitochondrial BER pathway were measured after 30-min
preincubation of isolated mitochondria at 25-40 degrees C and one of them, uracil
glycosylase, was completely inhibited at 40 degrees C. We conclude that cell
viability, respiration and DNA repair have different temperature sensitivities
between 25 and 37 degrees C, and that they are all very sensitive to 40 or 42
degrees C. Thus, A. angustifolia will likely be vulnerable to the short-term high
temperature events associated with global warming.
PMID- 29952011
TI - Diagnostic features of acquired dermal melanocytosis of the face and extremities.
AB - Acquired dermal melanocytosis of the face and extremities (ADMFE) is an unusual
form of acquired dermal melanocytosis (ADM). In this paper, we report a case of
ADMFE and review the published literature. Our review highlights several clinical
differences between ADMFE and ADM: (i) more frequent involvement of the nasal
alae in ADMFE than in ADM, (ii) less frequent involvement of the cheeks in ADMFE
than in ADM, (iii) limbs affected in all cases of ADMFE but in few cases of ADM,
and (iv) frequent involvement of conjunctiva and/or gingiva in ADMFE but very
rare involvement in ADM. These findings strongly support the hypothesis that
ADMFE is clinically distinct from the classic form of ADM, and gaining an
understanding of its phenotype will enable accurate diagnosis and early
intervention by Q-switched laser therapy, which should benefit those patients
with disease-related cosmetic issues.
PMID- 29952012
TI - Chlororespiration induces non-photochemical quenching of chlorophyll fluorescence
during darkness in lichen chlorobionts.
PMID- 29952013
TI - Interferon-free therapy in hepatitis C virus mixed cryoglobulinaemia: a
prospective, controlled, clinical and quality of life analysis.
AB - BACKGROUND: Cryoglobulinaemic vasculitis (CV) is a lymphoproliferative disorder
related to hepatitis C virus (HCV) infection; anti-viral therapy is the first
therapeutic option. CV can be incapacitating, compromising the patients' quality
of life (QoL). In a controlled study, interferon-based therapy was associated
with a lower virological response in vasculitic patients than in patients without
vasculitis. Limited, uncontrolled data on direct-acting anti-virals are
available. AIM: To evaluate safety, clinical efficacy, virological response and
the impact of interferon-free treatment on QoL in HCV patients with and without
mixed cryoglobulinaemia (MC). METHODS: We prospectively studied HCV patients with
cryoglobulinaemia (with vasculitis-CV- and without vasculitis-MC-) and without
cryoglobulinaemia (controls), treated with direct-acting anti-virals. Hepato
virological parameters, CV clinical response and impact on QoL were assessed.
RESULTS: One hundred and eighty-two HCV patients were recruited (85 with CV, 54
with MC and 43 controls). A sustained virological response at 12 weeks (SVR12)
was achieved in 166 (91.2%) patients (77/85 CV, 48/54 MC, 41/43 controls). In CV
SVR patients, cryocrit levels progressively decreased and clinical response
progressively improved, reaching 96.7%, 24 weeks after treatment. QoL, baseline
physical and mental component summaries were lower in the CV group compared to
the other groups (P < 0.05). Scores improved in all groups, and significantly in
CV patients after SVR. CONCLUSIONS: No significant differences in SVR rates were
recorded between cryoglobulinaemic patients and controls and a high clinical and
immunological efficacy was confirmed in CV, supporting the role of interferon
free therapy as the first therapeutic option. Interestingly, CV patients had
worse baseline QoL than other HCV-positive groups and interferon-free therapy was
effective in significantly increasing QoL, suggesting the important role of
direct-acting anti-viral-based therapy in improving CV's individual and social
burden.
PMID- 29952014
TI - Role of pannexin 1 channels in load-induced skeletal response.
AB - The pannexin 1 (Panx1) channel is a mechanosensitive channel that interacts with
P2X7 receptors (P2X7R) to form a functional complex that has been shown in vitro
to play an essential role in osteocyte mechanosignaling. While the participation
of P2X7R in skeletal responses to mechanical loading has been demonstrated, the
role of Panx1 and its interplay with P2X7R still remain to be determined. In this
study, we use a global Panx1-/- mouse model and in vivo mechanical loading to
demonstrate that Panx1 channels play an essential role in load-induced skeletal
responses. We found that absence of Panx1 not only disrupts the P2X7R-Panx1
signaling complex, but also alters load-induced regulation of P2X7R expression.
Moreover, lack of Panx1 completely abolished load-induced periosteal bone
formation. Load-induced regulation of beta-catenin and sclerostin expression was
dysregulated in Panx1-/- , compared to wild-type, bone. This finding suggests
that Panx1 deficiency disrupts Wnt/beta-catenin signaling by lowering beta
catenin while favoring inhibition of bone formation by increasing load-induced
sclerostin expression. This study demonstrates the existence of a Panx1-dependent
mechanosensitive mechanism that not only modulates ATP signaling but also
coordinates Wnt/beta-catenin signaling that is essential for proper skeletal
response to mechanical loading.
PMID- 29952016
TI - Cutaneous manifestations of metastatic Crohn's disease.
AB - Metastatic Crohn's disease is a rare cutaneous complication of primary Crohn's
disease. It is a granulomatous inflammatory process, similar to the pathogenic
mechanism of Crohn's disease, that occurs in sites discontiguous from the
gastrointestinal tract. Metastatic Crohn's disease can precede the development of
Crohn's disease by months to years, and children are more likely to present with
metastatic Crohn's disease in the absence of gastrointestinal symptoms. Given
that approximately 30% of individuals with Crohn's disease present in childhood,
early recognition of extraintestinal manifestations of Crohn's disease such as
metastatic Crohn's disease can aid in timely diagnosis and management of bowel
disease. We present data from two pediatric cases of metastatic Crohn's disease
recently seen at our institution in addition to the 61 reported cases of
pediatric metastatic Crohn's disease in the literature. This review article will
focus on the epidemiology, pathogenesis, clinical features, and histology of and
treatment options for pediatric metastatic Crohn's disease.
PMID- 29952017
TI - Congenital nevus comedonicus complicated by a hidradenitis suppurativa-like
lesion: Report of a childhood case.
AB - Nevus comedonicus is a rare, benign hamartoma of the pilosebaceous unit that may
be isolated or part of the nevus comedonicus syndrome. Although rare in children,
complication by hidradenitis suppurativa-like lesions has been described. We
present a report of a 9-year-old girl in whom surgical excision was curative,
with a review of the relevant literature.
PMID- 29952018
TI - Mycoplasma pneumoniae-associated mucositis with severe blistering stomatitis and
pneumonia successfully treated with azithromycin and infusion therapy.
PMID- 29952015
TI - C-reactive protein during and after myocardial infarction in relation to cardiac
injury and left ventricular function at follow-up.
AB - BACKGROUND: Acute myocardial infarction (MI) invokes a large inflammatory
response, which contributes to myocardial repair. HYPOTHESIS: We investigated
whether C-reactive protein (CRP) measured during MI vs at 1 month follow-up
improves the prediction of left ventricular (LV) function. METHODS: We
prospectively enrolled 131 consecutive patients with acute MI and without non
cardiovascular causes of inflammation. We correlated admission and peak levels of
CRP during hospitalization and high-sensitivity (hs) CRP at 1 month follow-up
with markers of cardiac injury. Clinical follow-up and echocardiography for LV
function were performed at a mean of 17 months. RESULTS: Median CRP levels were
1.89 mg/L on admission with MI, peaked to 12.10 mg/L during hospitalization and
dropped to 1.24 mg/L at 1 month. Although admission CRP levels only weakly
correlated with ejection fraction in the acute phase of MI (coefficient -0.164, P
= 0.094), peak CRP was significantly related to ejection fraction (coefficient
0.4, P < 0.001), hsTroponin T (0.389, P < 0.001), and white blood cell count
(0.389, P < 0.001). hsCRP at 1 month was not related to the extent of acute
cardiac injury. These findings were replicated in an independent cohort of 57
patients. Peak CRP predicted LV dysfunction at follow-up (OR 11.0, 3.1-39.5 per
log CRP, P < 0.001), persisting after adjustment for infarct size (OR 5.1, 1.1
23.6, P = 0.037), while hsCRP at 1 month was unrelated to LV function at follow
up. CONCLUSIONS: hsCRP 1 month post-MI does not relate to acute cardiac injury or
LV function at follow-up, but we confirm that peak CRP is an independent
predictor of LV dysfunction at follow-up.
PMID- 29952019
TI - Prolonged growth of infantile hemangioma after pulsed dye laser and oral
propranolol treatment.
AB - Infantile hemangiomas are the most common tumor of childhood and undergo rapid
growth during early infancy followed by gradual involution. After involution,
residual lesions sometimes remain. Oral propranolol usually induces earlier
involution and redness reduction of infantile hemangiomas. However, the optimal
treatment duration is unknown and infantile hemangiomas sometimes recur after
cessation of treatment. We report three Japanese patients with recurrent
infantile hemangiomas on their cheek. These patients were a 1-month-old female
baby with a superficial infantile hemangioma, a 3-month-old female baby with a
mixed infantile hemangioma and a 4-month-old male baby with a mixed infantile
hemangioma. Two of them also received pulsed dye laser treatment. They did not
reach complete or nearly complete resolution of infantile hemangiomas at week 25.
These patients experienced regrowth of their infantile hemangioma after 20 months
of age and took propranolol after the age of 24 months. There were no severe
adverse effects. Propranolol may not only be therapeutic but also prophylactic.
Patients with infantile hemangiomas who have taken oral propranolol should be
followed up at least 6 months after cessation of treatment, especially infantile
hemangiomas on the cheek, and those with partial response to propranolol may
require close attention in prolonged growth.
PMID- 29952020
TI - A case of scalp necrosis.
PMID- 29952021
TI - Psoriasiform dermatitis associated with common variable immunodeficiency 10 due
to an Arg853* mutation in the NFKB2 gene.
PMID- 29952022
TI - The impact of transplant rejection on cutaneous squamous cell carcinoma in renal
transplant recipients.
AB - BACKGROUND: The incidence of cutaneous squamous cell carcinoma (cSCC) is markedly
increased in renal transplant recipients compared with that of the nontransplant
population. AIM: To investigate whether there is a relationship between
transplant rejection and cSCC. METHODS: The Duke Enterprise Data Unified Content
Explorer historical database was used to identify patients who had undergone a
renal transplant at Duke University Hospital during a 20-year period. Data on
patient demographics, transplant dates, first rejection episodes, first cSCC
development, medication, laboratory results and survival were recorded. RESULTS:
In total, 1684 patients were identified, of whom 126 (7.5%) experienced an
episode of rejection and 46 (4.0%) developed a cSCC after transplant. The
incidence of cSCC was significantly greater in the rejection group, with 8.7% of
patients developing cSCC compared with 2.2% in the no-rejection group (P <
0.001). Median lag time to cSCC was shorter in the rejection group (2.5 years;
age 0.4-9.0 years) than the no-rejection group (4.2 years; range 1.3-20.4 years)
(P < 0.03). CONCLUSIONS: Transplant rejection is associated with both a higher
incidence and an accelerated time course for development of cSCC following renal
transplantation. Close dermatological surveillance should be considered following
an episode of rejection in this patient population.
PMID- 29952023
TI - Successful treatment of erythematotelangiectatic rosacea with intense pulsed
light: Report of 13 cases.
AB - Here, we describe the use of intense pulsed light (IPL) treatment for 13 cases of
erythematotelangiectatic rosacea delivered in three sessions. For two-step
irradiation, after the whole face had been irradiated using conventional IPL
equipment covering a wide area, localized IPL spot irradiation was performed for
visibly dilated capillaries. The therapeutic effect was evaluated by image
analysis using Image J and scored by 10 dermatologists using two IPL instruments
in combination. This therapeutic approach was found to be much more effective
than irradiation using a single instrument. Our findings demonstrate that IPL
irradiation using the present method can deliver a sufficient therapeutic effect
even with a small number of treatment sessions. Although rosacea is difficult to
treat, we believe that IPL can be therapeutically useful in such cases.
PMID- 29952024
TI - Sezary syndrome in an anti-human T-cell lymphotropic virus type 1 seropositive
carrier.
PMID- 29952025
TI - Gastrointestinal: Multiple venous malformations and polyps of the small intestine
in Cowden syndrome.
PMID- 29952026
TI - Injectable Oxygen: Interfacing Materials Chemistry with Resuscitative Science.
AB - Intravascular oxygen delivery holds great potential to treat numerous hypoxic
conditions and emergencies, including pulmonary disorders, hypoxic tumors,
hemorrhagic shock, stroke, cardiac arrest and so on. Tremendous effort has been
made in the past to find material solutions for the development of intravenous
oxygen carriers and have ranged from blood substitutes to microbubbles with
limited success. This paper highlights previous and recent progress in
perfluorocarbon-emulsions and microbubbles as intravenous gas carriers, including
concerns over their long-term stability, in vivo safety profiles, and oxygen
transport efficacy. Their use as potential resuscitative therapeutics for
treating various types of cardiac arrest is also discussed.
PMID- 29952027
TI - Effect of bone marrow mesenchymal stem cells on healing of temporomandibular
joints in rats with induced rheumatoid arthritis.
AB - The healing capacity of bone marrow mesenchymal stem cells (BMMSCs) has been
evaluated in various studies. This study aimed to evaluate the effect of BMMSCs
on the healing of temporomandibular joints (TMJs) with induced rheumatoid
arthritis. Fifty healthy male Sprague Dawley rats were divided into three groups:
group I (n = 10), negative control; group II (n = 20), positive control
(induction of arthritis by adjuvant followed by intravenous injection of 0.1 ml
of PBS); and group III (n = 20), intervention (as for group II but injected
intravenously with 1 * 106 cells ml-1 of BMMSCs suspended in PBS). Half of the
rats in each group were euthanized 3 wk after the start of the experiment and the
other half was euthanized after 5 wk. Group I revealed normal TMJ features. Group
II showed thickening of disc, thinning of cartilage, disordered bone trabeculae,
and decreased in mean % area staining positive of collagen fibers at 3 wk, while
at 5 wk these effects were more aggravated. Group III showed nearly normal
thickness of disc and condylar cartilage, nearly normal arrangement of bone
trabeculae and regenerated collagen fibers at 3 wk, while after 5 wk the TMJ
features were almost normal. Two-way anova revealed statistically significant
differences between groups. Thus, treatment of induced rheumatoid arthritis with
BMMSCs shows promising results that need to be further investigated in humans.
PMID- 29952028
TI - Efficacy of essential oils combination on performance, ileal bacterial counts,
intestinal histology and immunocompetence of laying hens fed alternative lipid
sources.
AB - This study was carried out to assess the effects of a blend of herbal essential
oils (namely Thymus vulgaris, Mentha piperita, Rosmarinus offisinalis and Anethum
graveolens) and different dietary lipid sources on the performance, ileal
bacterial enumeration, intestinal histological alterations and immune responses
in laying hens. For this purpose, a total of 150 laying hens were randomly
allocated to six experimental treatments with five replicates of five birds each.
Dietary treatments consisted of three levels of a mixture of essential oils (0,
100 and 200 mg/kg) and two sources of lipid (soybean oil and fish oil containing
different ratios of n-6 to n-3 fatty acids) fed to the animals during an 80-days
feeding trial. Findings indicated that dietary administration of fish oil not
only increased significantly the spleen relative weight (p < 0.01) and the
antibody titre against Newcastle virus (p < 0.05) but also led to reductions in
liver relative weight (p < 0.05) and feed conversion ratio (p < 0.05). Moreover,
the mixture of herbal essential oils brought about declines in hepatic relative
weight, heterophile to lymphocyte ratio (p < 0.05) and intestinal pathogen
populations (p < 0.01). Mention must also be made of the improvements it made in
spleen weight (p < 0.01), antibody titres against SRBC (p < 0.01) and Newcastle
virus (p < 0.05), villus height to crypt depth ratio (p < 0.01), goblet cell
numbers (p < 0.05), lamina propria lymphatic follicle diameters (p < 0.01) and
feed conversion ratio (p = 0.06). It may be claimed that the enhancements
observed in the performance of laying hens fed fish oil and 200 mg/kg of the
blend of essential oils could have potentially been associated with improved
intestinal health indices as well as cellular and humoral immune responses.
PMID- 29952029
TI - DNA physical interaction mediated b-lymphoma treatment offered by tetra
benzimidazole-substituted zinc (ii) phthalocyanine derivative.
AB - Role of heterocyclic compounds with nitrogen substitution in therapeutic
frontiers is well established. The efforts made in this study are directed to
dissect the biological significance of benzimidazole-substituted zinc
phthalocyanine derivative. Its capacity to act as an anticancer agent against the
2 B-lymphoma cell lines (low-grade and high-grade malignancy) was found out by
recording florescence using Alamar blue dye. Further cytotoxic effect at the DNA
level was analyzed by performing agarose gel electrophoresis. Molecular docking
studies made mechanistic details crystal clear by showing potential dual binding
modes employed for interaction with DNA that include minor groove binding and
intercalation between bases. This advocates this derivative as potential
anticancer agent and deserves further rounds of mechanistic study for its final
journey to serve as a marketed drug.
PMID- 29952030
TI - Continuous Fabrication of Meter-Scale Single-Wall Carbon Nanotube Films and their
Use in Flexible and Transparent Integrated Circuits.
AB - Single-wall carbon nanotubes (SWCNTs), especially in the form of large-area and
high-quality thin films, are a promising material for use in flexible and
transparent electronics. Here, a continuous synthesis, deposition, and transfer
technique is reported for the fabrication of meter-scale SWCNT thin films, which
have an excellent optoelectrical performance including a low sheet resistance of
65 Omega/? with a transmittance of 90% at a wavelength of 550 nm. Using these
SWCNT thin films, high-performance all-CNT thin-film transistors and integrated
circuits are demonstrated, including 101-stage ring oscillators. The results pave
the way for the future development of large-scale, flexible, and transparent
electronics based on CNT thin films.
PMID- 29952031
TI - Carbonic anhydrase IX is a prognostic biomarker in glioblastoma multiforme.
AB - The identification of prognostic factors in patients with glioblastoma multiforme
(GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA-IX), a
hypoxia marker, correlates with tumor progression in a variety of human cancers.
However, the role of CA-IX in GBM remains largely unknown. In the present study,
we evaluated the prognostic role of CA-IX in GBM patients. In total, 66
consecutive patients with GBM who received concomitant chemoradiotherapy and
adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all
patients received temozolomide chemotherapy for at least 3 months. Kaplan-Meier
curves and log-rank tests were used for analysis of progression-free survival
(PFS) and overall survival (OS), and a multivariate Cox proportional hazard model
was employed to identify factors with an independent effect on survival. The
median OS was longer in patients with low levels of CA-IX expression (18 months)
compared to patients overexpressing CA-IX (9 months) (P = 0.004). There was not a
statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054)
between patients with high or low levels of CA-IX expression. In multivariate
analysis, the variables that were identified as significant prognostic factors
for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio
(HR), 3.703; P = 0.001), CA-IX overexpression (HR, 1.967; P = 0.019), and
incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross-total
resection (HR, 1.956; P = 0.034). Our findings indicated that CA-IX may be a
potential prognostic biomarker in the treatment of GBM.
PMID- 29952032
TI - The influence of iatrogenic interatrial septum leaks after left atrial appendage
closure on cardiac function test results.
AB - AIM: Left atrial appendage occlusion (LAAO) is a technique for preventing
thromboembolism in patients with atrial fibrillation and a high risk of
irreversible bleeding. In some patients, a spontaneous iatrogenic transseptal
leak (ITL) remains after LAAO. The aim of this study was to assess the
correlation between ITL incidence and the results of cardiac function tests in
patients who underwent LAAO. METHODS AND RESULTS: LAOO was performed in 62
consecutive patients using the Amplatzer Amulet. Before and 3 months after LAA
occlusion, the 6-min walking distance (6MWD) test was performed in all patients
and oxygen consumption assessment (VO2max ) was performed in 32. All patients had
transesophageal echocardiography before and 3 months after LAAO to assess ITL
incidence. The patients were divided according to the presence and absence of ITL
and the subgroup of patients with heart failure (HF) were further analyzed. In
patients with HF and ITL, an increased VO2max (12.8 +/- 5.2 vs 15.3 +/- 4.7; P <
0.05) and 6MWD (350.1 +/- 77.4 vs 414.3 +/- 70.6; P < 0.05) was observed after
the procedure comparing to the results before the procedure. The 6MWD was also
significantly higher in the patients with transseptal leaks in comparison to
those without (P < 0.0001). CONCLUSION: The presence of transseptal leaks after
LAAO does not influence overall cardiac function test results. However, in
patients with HF, there is an increase in oxygen consumption and 6MWD. These
results indicate that ITLs in patients with HF decrease left atrial pressure,
which is the key contributor to the symptoms of heart failure during physical
activity.
PMID- 29952033
TI - Profilometric changes of peri-implant tissues over 5 years: A randomized
controlled trial comparing a one- and two-piece implant system.
AB - OBJECTIVES: To assess the profilometric changes of the buccal soft tissues
between baseline and 5 years of loading using a one- and two-piece dental implant
system. MATERIALS AND METHODS: Sixty patients randomly received dental implants
of either a two-piece type (BRA) or a one-piece type (STM). Casts were obtained
at baseline (after crown insertion), at the 1-year and at the 5-year follow-up.
Stereolithography files were obtained from the casts for digital superimposition.
One implant and the contralateral natural tooth were selected for the analysis.
Thirty-three patients (BRA = 16; STM = 17) were included. Measurements included
changes for crown height (CH) and estimated soft tissue thickness, as well as the
profilometric change at the implant and the tooth site. Nonparametric methods
were applied for the statistical analyses and medians and quartiles presented.
RESULTS: The BRA group lost -0.39 mm and the STM group lost -0.40 mm of volume
between baseline and the 5-year follow-up at the implant site (p > 0.05). The
tooth site lost -0.18 mm (BRA) and -0.12 mm (STM) (p > 0.05). Volume differences
between implants and teeth amounted to -0.05 mm (baseline to 1 year) and -0.25 mm
(baseline to 5 years) for BRA, while for STM, the values were 0.03 mm (baseline
to 1 year) and -0.16 mm (baseline to 5 years). The changes for implant CH at 1
and 5 years of follow-up amounted 0.10 and 0.09 mm (BRA) and to 0.03 and 0.22 mm
(STM). The changes in tissue thickness at 1 and 5 years in the BRA group amounted
to -0.28 and -0.66 mm at 1 mm, -0.21 and -0.46 mm at 3 mm, and -0.32 and -0.45 mm
at 5 mm, respectively. The changes in the STM group amounted to -0.15 and -0.54
mm at 1 mm, -0.24 and -0.48 mm at 3 mm, and -0.32 and -0.57 mm at 5 mm,
respectively. No significantly different medians were observed. CONCLUSIONS:
Minimal profilometric and linear changes occurred at implant sites between
baseline and 5 years, between implant and tooth sites and between the two implant
systems.
PMID- 29952034
TI - Hyperporous Sponge Interconnected by Hierarchical Carbon Nanotubes as a High
Performance Potassium-Ion Battery Anode.
AB - Recently, commercial graphite and other carbon-based materials have shown
promising properties as the anode for potassium-ion batteries. A fundamental
problem related to those carbon electrodes, significant volume expansion, and
structural instability/collapsing caused by cyclic K-ion intercalation, remains
unsolved and severely limits further development and applications of K-ion
batteries. Here, a multiwalled hierarchical carbon nanotube (HCNT) is reported to
address the issue, and a reversible specific capacity of 232 mAh g-1 , excellent
rate capability, and cycling stability for 500 cycles are achieved. The key
structure of the HCNTs consists of an inner CNT with dense-stacked graphitic
walls and a loose-stacked outer CNT with more disordered walls, and individual
HCNTs are further interconnected into a hyperporous bulk sponge with huge
macropore volume, high conductivity, and tunable modulus. It is discovered that
the inner dense-CNT serves as a robust skeleton, and collectively, the outer
loose-CNT is beneficial for K-ion accommodation; meanwhile the hyperporous sponge
facilitates reaction kinetics and offers stable surface capacitive behavior. The
hierarchical carbon nanotube structure has great potential in developing high
performance and stable-structure electrodes for next generation K and other metal
ion batteries.
PMID- 29952035
TI - Transplant advocacy in the era of the human immunodeficiency virus organ policy
equity act.
AB - In 2013, the Human Immunodeficiency Virus Organ Policy Equity (HOPE) Act was
passed to permit the conduct of research on the transplantation of organs from
donors infected with human immunodeficiency virus (HIV) into recipients who are
HIV-positive. The HOPE Act workshop had many objectives including the discussion
of the ethical issues involved in HIV-positive to HIV-positive transplantation,
the informed consent process, and the role of independent advocates in the
context of HIV to HIV transplantation. As of 2018, 22 transplant hospitals are
approved, or undergoing approval, to perform HIV-positive to HIV-positive
transplant surgeries, and this number is expected to grow. This study aims to:
(i) briefly review the history and research of HIV+ transplantation prior to the
HOPE Act, (ii) describe the ethical principles supporting the HOPE Act, (iii)
characterize the informed consent process, and (iv) provide guidance regarding
the role of independent advocates in the context of HIV-positive to HIV-positive
transplantation.
PMID- 29952036
TI - Host-Guest and Photophysical Behavior of Ti8 L12 Cube with Encapsulated [Ti(H2
O)6 ] Species.
AB - Titanium-based coordination cages could be interesting for both supramolecular
and photophysical chemistry. This work reports an unprecedented host-guest
system, [Ti(H2 O)6 ]@Ti8 L12 , which is comprised of the first Ti-based
coordination cube and the unusual titanium aquo species. Due to the abundant
intra-cube O-H???O hydrogen bonds, the [Ti(H2 O)6 ]@Ti8 L12 complex is rather
stable both in solid and solution states, confirmed by X-ray diffraction and ESI
MS analysis. The encapsulated [Ti(H2 O)6 ] species shows influence on the light
absorption, photoluminescent, and photocurrent properties. Moreover, ultrafast
transient absorption spectroscopy has been applied to study the photodynamics of
both free and [Ti(H2 O)6 ] guest encapsulated Ti8 L12 cube, confirming that the
host-guest system produces a slightly longer-lived excited state. Therefore, this
work presents the first [Ti8 L12 ] cube with unusual [Ti(H2 O)6 ] guest and also
provides an interesting supramolecular model for the host-guest photophysical
study.
PMID- 29952037
TI - ATP6V0A2-related cutis laxa in 10 novel patients: Focus on clinical variability
and expansion of the phenotype.
AB - In ATP6V0A2-related cutis laxa, the skin phenotype varies from a wrinkly skin to
prominent cutis laxa and typically associates with skeletal and neurological
manifestations. The phenotype remains incompletely characterized, especially in
adult patients. Glycosylation defects and reduced acidification of secretory
vesicles contribute to the pathogenesis, but the consequences at the clinical
level remain to be determined. Moreover, the morphology of the elastic fibres has
not been studied in ATP6V0A2-related cutis laxa, nor its relation with potential
clinical risks. We report on the extreme variability in ATP6V0A2-related cutis
laxa in 10 novel patients, expand the phenotype with emphysema and von Willebrand
disease and hypothesize on the pathogenesis that might link both with deficiency
of glycosylation and with elastic fibre anomalies. Our data will affect clinical
management of patients with ATP6V0A2-related cutis laxa.
PMID- 29952038
TI - Urinary matrix effects in electrospray ionization mass spectrometry in the
presence of DMSO.
PMID- 29952039
TI - Outcomes of Patients with Autosomal Dominant Polycystic Kidney Disease on
Peritoneal Dialysis: A Meta-Analysis.
AB - BACKGROUND: Complications related to peritoneal dialysis (PD) in patients with
autosomal dominant polycystic kidney disease (ADPKD) including intraperitoneal
rupture of renal cyst, hernia, membrane failure, and peritonitis have been
reported. However, long-term clinical outcomes of ADPKD patients on PD remain
unclear. We performed this meta-analysis to assess the risks of death, technique
failure, and peritonitis in ADPKD patients on PD. METHODS: A systematic review
was conducted using MEDLINE, EMBASE, Cochrane databases from inception through
October 2017 to identify studies that evaluated outcomes of ADPKD patients on PD
including the risks of death, technique failure, and peritonitis. Non-ADPKD
patients on PD were used as controls. Effect estimates from the individual study
were extracted and combined using random-effect, generic inverse variance method
of DerSimonian and Laird. RESULTS: Twelve cohort studies with a total of 14,673
patients on PD (931 ADPKD and 13,742 non-ADPKD patients) were enrolled. Compared
with non-ADPKD status, ADPKD was associated with significantly decreased
mortality risk with pooled OR of 0.68 (95% CI, 0.53-0.86, I2 = 0). There were no
associations of ADPKD with the risks of technique failure of PD and peritonitis
with pooled ORs of 0.93 (95% CI, 0.79-1.10, I2 = 0) and 0.88 (95% CI, 0.75-1.05,
I2 = 0), respectively. We found no publication bias as assessed by Egger's
regression asymmetry test with p= 0.90, 0.28 and 0.60 for the risks of mortality,
technique failure, and peritonitis in ADPKD patients on PD, respectively.
CONCLUSIONS: Compared with non-ADPKD patients on PD, our study demonstrates that
ADPKD patients on PD have 0.68-fold decreased mortality risk. There are no
associations of ADPKD status with the risks of technique failure or peritonitis.
This article is protected by copyright. All rights reserved.
PMID- 29952040
TI - Egg product freshness evaluation: A metabolomic approach.
AB - Egg products' freshness is a crucial issue for the production of safe and high
quality commodities. Up to now, this parameter is assessed with the
quantification of few compounds, but the possibility to evaluate more molecules
simultaneously could help to provide robust results. In this study, 31 compounds
responsible of freshness and not freshness of egg products were selected with a
metabolomic approach. After an ultrahigh-pressure liquid chromatography-high
resolution mass spectrometry (UHPLC-HRMS) analysis, different chemometric models
were created to select gradually the most significant features that were finally
extracted and identified through HRMS data. Sample lots were collected directly
from their arrival at the production plant sites, extracted immediately after,
then left at room temperature, and extracted again after 24 and 48 hours (first
day and second day, respectively). A total amount of 79 samples was used for the
model creation. Furthermore, the same compounds were detected in seven new egg
products sample lots not used for the model creation and treated with the same
experimental design (total amount of samples, 21). The results obtained clearly
demonstrate that these 31 molecules can be considered real freshness or not
freshness chemical markers. Furthermore, this UHPLC-HRMS metabolomic approach
allows for the detection of a larger set of metabolites clearly related to
possible microbial growth over time, which is a relevant point for also ensuring
food safety.
PMID- 29952041
TI - DNA Block Macromolecules Based on Rolling Circle Amplification Act as Scaffolds
to Build Large-Scale Origami Nanostructures.
AB - A simplified origami strategy to create large-scale complex DNA nanostructures
based on the rolling circle amplification (RCA) is developed. The long repetitive
block single strand DNA (ssDNA) synthesized from RCA with a few staple strands
are used to fabricate DNA origami, which can be assembled into the first level
assemblies of micro-scale length mono-nanoladders. Depending on base pairing
among the sticky ends of short staple strands in nanoladders, the second level
assemblies with large-scale and controlled structures such as tri-nanoladder,
penta-nanoladder, and even nanobrocade, can be further achieved.
PMID- 29952042
TI - Intra-isthmus atrial flutter visualized with ultra-high resolution mapping.
PMID- 29952043
TI - MicroRNA-351-5p aggravates intestinal ischaemia/reperfusion injury through the
targeting of MAPK13 and Sirtuin-6.
AB - BACKGROUND AND PURPOSE: Intestinal ischaemia-reperfusion (II/R) injury is a
serious clinical problem. Here we have investigated novel mechanisms and new drug
targets in II/R injury by searching for microRNAs regulating such injury.
EXPERIMENTAL APPROACH: We used hypoxia/reoxygenation (H/R) of IEC-6 cell cultures
and models of II/R models in rats and mice. Microarray assays were used to
identify target miRNAs from rat intestinal. Real-time PCR, Western blot and dual
luciferase reporter assays, and agomir and antagomir in vitro and in vivo were
used to assess the effects of the target miRNA on II/R injury. KEY RESULTS: The
miR-351-5p was differentially expressed in our models and it targeted MAPK13 and
sirtuin-6. This miRNA reduced levels of sirtuin-6 and AMP-activated protein
kinase phosphorylation, and activated forkhead box O3 (FoxO3alpha)
phosphorylation to cause oxidative stress. Also, miR-351-5p markedly reduced
MAPK13 level, activated polycystic kidney disease 1/NF-kappaB signal and
increased NF-kappaB (p65). Moreover, miR-351-5p up-regulated levels of Bcl2
associated X, cytochrome c, apoptotic peptidase activating factor 1, cleaved
caspase 3 and cleaved-caspase 9 by reducing sirtuin-6 levels to promote
apoptosis. In addition, miR-351-5p mimic in IEC-6 cells and agomir in mice
aggravated these effects, and miR-351-5p inhibitor and antagomir in mice
alleviated these actions. CONCLUSIONS AND IMPLICATIONS: Our data showed that miR
351-5p aggravated II/R injury by promoting intestinal mucosal oxidative stress,
inflammation and apoptosis by targeting MAPK13 and sirtuin-6.These data provide
new insights into the mechanisms regulating II/R injury, and of miR-351-5p could
be considered as a novel therapeutic target for such injury.
PMID- 29952044
TI - NonPharmacological interventions for managing wandering in the community: A
narrative review of the evidence base.
AB - Dementia-related wandering is exhibited by as many as 63% of people with dementia
living in the community. There is strong evidence that people with dementia who
wander are at risk of life-threatening outcomes including injury from falls,
exhaustion, weight loss, and becoming lost. Furthermore, carers have reported
that fear of a person with dementia becoming lost contributes to them taking
extreme measures in an attempt to maintain safety at home and there are few
guidelines to direct care practices. Previous literature reviews of interventions
to manage wandering have been inconclusive as the quality of research resulted in
most studies being excluded. This narrative review aimed to report on the current
state of wandering intervention science for people with dementia cared for in the
community. An extensive search of articles and grey literature published between
January 1999 and November 2017 was conducted and included quantitative studies
that reported findings of nonpharmacological interventions for people with
dementia living in the community that reported outcome measures of wandering
characteristics (e.g., frequent ambulation, pacing, and boundary transgression).
Eleven papers met the inclusion criteria, the majority of which were small
nonrandomised studies or case studies with interventions that focused on:
engaging the person with dementia in an activity, improving safety with
environmental modifications, and technology to improve navigation or to monitor
movement. While the strength of the evidence was low, the review has identified
some promising interventions that carers of people with dementia could trial to
reduce risky aspects of wandering, as well as identifying potential directions
for future research.
PMID- 29952045
TI - Using the "proportion of patients covered" and the Kaplan-Meier survival analysis
to describe treatment persistence.
AB - PURPOSE: Standard Kaplan-Meier (KM) survival analysis is often used to study
treatment persistence estimating the proportion of patients who have not yet
experienced a treatment break by a given day after treatment initiation. This
method only allows patients to be studied until their first treatment break. The
"proportion of patients covered" (PPC) method is another approach to study
treatment persistence. It measures the proportion of live patients currently
covered by treatment. We aimed to describe the PPC method, show how the KM
survival analysis and the PPC method can describe treatment persistence, and
discuss the interpretation/application of the methods. METHODS: We identified new
users of statins, selective serotonin reuptake inhibitors, hormone replacement
therapy, and ibuprofen. We used KM estimates and the PPC to describe persistence
in the 3 years post treatment initiation, using a grace period of 90 days to
define a treatment break. RESULTS: Three years after statin initiation,
approximately 40% of patients were still in continuous treatment (KM survival)
and 60% of patients still alive were in current treatment (PPC). Corresponding
numbers were 12% and 25% for selective serotonin reuptake inhibitors and 9% and
29% for hormone replacement therapy. At 1 year, numbers were 5% and 10% for
ibuprofen. The PPC showed markedly less variability than the KM survival analysis
with different choices of grace periods. CONCLUSIONS: The KM survival analysis
and the PPC method can be used to study different aspects of treatment
persistence. Together, they provide a more complete picture of treatment
persistence and drug use patterns.
PMID- 29952046
TI - Perceived doctor-patient relationship and its association with demoralization in
patients with advanced cancer.
AB - BACKGROUND: Advanced diseases pose a great burden on patients and go hand in hand
with existential concerns. Demoralization is considered as a syndrome of
existential distress with a perceived inability to cope with loss of meaning in
life and feelings of helplessness and hopelessness. Professional health care
providers play an important role in providing support for patients and
unfavorable conversational styles in their relationship can increase patient's
distress. In this study, we examine the association between the patient's
perceived relationship to health care providers and demoralization. METHODS: We
used baseline data of a randomized control trial intervention study for advanced
cancer patients (UICC-Stage >= III; PHQ >= 9 and/or Distress-Thermometer >=5). We
used a subscale of the QUAL-EC-P for assessing doctor-patient relationship, Beck
Depression Inventory-II for depressive symptoms, a modified version of the MSAS
as physiological symptom checklist, and the Demoralization Scale to assess
demoralization. A hierarchical regression analysis was calculated. RESULTS: In
our sample of 187 patients with stage III or IV cancer (62% women),
demoralization was present in 53.4% (16% moderate demoralization; 37.4% high
demoralization) of the patients. Relationship to health care provider was an
independent predictor (beta = -.33, t(186) = -6.70, P < .001) of demoralization.
CONCLUSIONS: Our findings underline the importance of the physician-patient
relationship in the context of coping with existential challenges in advanced
cancer patients. Trainings on how to communicate and build a sustainable
relationship with patients and their specific needs may increase the buffering
effect of social support by the physicians on patient's existential distress.
PMID- 29952047
TI - A randomized controlled trial of a supportive expressive group intervention for
women with a family history of breast cancer.
AB - OBJECTIVE: Women with a family history of breast cancer (BC) often overestimate
their BC risk. Heightened psychological distress may interfere with risk
comprehension and screening adherence. The primary purpose of this study was to
test the efficacy of a 12-week manual-based supportive-expressive (SE) group
intervention for this population. METHODS: Using a randomized control trial
design, this study compared two interventions: a standard risk-counseling arm
(RC) compared with that plus SE group intervention. The primary study outcome was
BC anxiety. Secondary outcomes included psychosocial functioning, risk
comprehension, BC knowledge, and screening behaviors. RESULTS: A total of 161
women with a family history of BC were randomized into SE (N = 108) or RC (N =
53). Participants in both study arms significantly improved on measures of BC
anxiety, psychosocial functioning, risk comprehension, and BC knowledge, with no
statistical difference between study arms. Benefits were sustained at 1 year. BC
screening rates were high in both arms at baseline and follow-up. CONCLUSIONS: SE
group therapy as an added intervention to the risk counseling was well-received,
however, did not demonstrate superiority to RC alone. Future studies on treatment
matching are needed to further our understanding of interventions that can
support women with a family history of BC to work through residual issues,
including loss and grief.
PMID- 29952049
TI - Empirical validation of the reverse parametric waiting time distribution and
standard methods to estimate prescription durations for warfarin.
AB - PURPOSE: In many prescription databases, the duration of treatment for the single
prescription is not recorded. This study aimed to validate 2 different types of
approaches for estimating prescription durations, using the oral anticoagulant
warfarin as a case. METHODS: The approaches undergoing empirical validation
covered assumptions of a fixed daily intake of either 0.5 or 1.0 defined daily
dose (DDD), as well as estimates based on the reverse parametric waiting time
distribution (rWTD), with different sets of covariates. We converted estimates of
prescription duration to daily dose and compared them to prescribed daily dose as
recorded in a clinical registry (using Bland-Altman plots). Methods were compared
based on their average prediction error (logarithmic scale) and their limit of
agreement ratio (ratio of mean error +/- 1.96 SD after transformation to original
scale). RESULTS: Estimates of daily doses were underestimated by 19% or
overestimated by 62% when assumptions of 0.5 or 1.0 DDD were applied. The limit
of agreement ratio was 6.721 for both assumptions. The rWTD-based approaches
performed better when using the estimated mean value of the inter-arrival
density, yielding on average negligible bias (relative difference of 0 to 2%) and
with limit of agreement ratios decreasing upon additional covariate adjustment
(from 6.857 with no adjustment to 4.036 with the fully adjusted model).
CONCLUSIONS: Comparing the different methods, the rWTD algorithm performed best
and led to unbiased estimates of prescribed doses and thus prescription durations
and reduced misclassification on the individual level upon inclusion of
covariates.
PMID- 29952048
TI - The genetic architecture of genome-wide recombination rate variation in
allopolyploid wheat revealed by nested association mapping.
AB - Recombination affects the fate of alleles in populations by imposing constraints
on the reshuffling of genetic information. Understanding the genetic basis of
these constraints is critical for manipulating the recombination process to
improve the resolution of genetic mapping, and reducing the negative effects of
linkage drag and deleterious genetic load in breeding. Using sequence-based
genotyping of a wheat nested association mapping (NAM) population of 2,100
recombinant inbred lines created by crossing 29 diverse lines, we mapped QTL
affecting the distribution and frequency of 102 000 crossovers (CO). Genome-wide
recombination rate variation was mostly defined by rare alleles with small
effects together explaining up to 48.6% of variation. Most QTL were additive and
showed predominantly trans-acting effects. The QTL affecting the proximal COs
also acted additively without increasing the frequency of distal COs. We showed
that the regions with decreased recombination carry more single nucleotide
polymorphisms (SNPs) with possible deleterious effects than the regions with a
high recombination rate. Therefore, our study offers insights into the genetic
basis of recombination rate variation in wheat and its effect on the distribution
of deleterious SNPs across the genome. The identified trans-acting additive QTL
can be utilized to manipulate CO frequency and distribution in the large
polyploid wheat genome opening the possibility to improve the efficiency of gene
pyramiding and reducing the deleterious genetic load in the low-recombining
pericentromeric regions of chromosomes.
PMID- 29952050
TI - Role of GhHDA5 in H3K9 deacetylation and fiber initiation in Gossypium hirsutum.
AB - Cotton fibers are single-celled trichomes that initiate from the epidermal cells
of the ovules at or before anthesis. Here, we identified that the histone
deacetylase (HDAC) activity is essential for proper cotton fiber initiation. We
further identified 15 HDACs homoeologs in each of the A- and D-subgenomes of
Gossypium hirsutum. Few of these HDAC homoeologs expressed preferentially during
the early stages of fiber development [-1, 0 and 6 days post-anthesis (DPA)].
Among them, GhHDA5 expressed significantly at the time of fiber initiation (-1
and 0 DPA). The in vitro assay for HDAC activity indicated that GhHDA5 primarily
deacetylates H3K9 acetylation marks. Moreover, the reduced expression of GhHDA5
also suppresses fiber initiation and lint yield in the RNA interference (RNAi)
lines. The 0 DPA ovules of GhHDA5RNAi lines also showed alterations in reactive
oxygen species homeostasis and elevated autophagic cell death in the developing
fibers. The differentially expressed genes (DEGs) identified through RNA-seq of
RNAi line (DEP12) and their pathway analysis showed that GhHDA5 modulates
expression of many stress and development-related genes involved in fiber
development. The reduced expression of GhHDA5 in the RNAi lines also resulted in
H3K9 hyper-acetylation on the promoter region of few DEGs assessed by chromatin
immunoprecipitation assay. The positively co-expressed genes with GhHDA5 showed
cumulative higher expression during fiber initiation, and gene ontology
annotation suggests their involvement in fiber development. Furthermore, the
predicted protein interaction network in the positively co-expressed genes
indicates HDA5 modulates fiber initiation-specific gene expression through a
complex involving reported repressors.
PMID- 29952051
TI - Carborane-Induced Excimer Emission of Severely Twisted Bis-o-Carboranyl Chrysene.
AB - The synthesis of a highly twisted chrysene derivative incorporating two electron
deficient o-carboranyl groups is reported. The molecule exhibits a complex,
excitation-dependent photoluminescence, including aggregation-induced emission
(AIE) with good quantum efficiency and an exceptionally long singlet excited
state lifetime. Through a combination of detailed optical studies and theoretical
calculations, the excited state species are identified, including an unusual
excimer induced by the presence of o-carborane. This is the first time that o
carborane has been shown to induce excimer formation ab initio, as well as the
first observation of excimer emission by a chrysene-based small molecule in
solution. Bis-o-carboranyl chrysene is thus an initial member of a new family of
o-carboranyl phenacenes exhibiting a novel architecture for highly-efficient
multi-luminescent fluorophores.
PMID- 29952052
TI - Predatory monetization schemes in video games (e.g. 'loot boxes') and internet
gaming disorder.
PMID- 29952053
TI - Synergistic Catalysis for the Umpolung Trifluoromethylthiolation of Tertiary
Ethers.
AB - The first transition-metal-free, site-specific umpolung trifluoromethylthiolation
of tertiary alkyl ethers has been developed, achieving the challenging tertiary
C(sp3 )-SCF3 coupling under redox-neutral conditions. The synergism of
organophotocatalyst 4CzIPN and BINOL-based phosphorothiols can site-selectively
cleave tertiary sp3 C(sp3 )-O ether bonds in complex molecules initiated by a
polarity-matching hydrogen-atom-transfer (HAT) event. The incorporation of
several competing benzylic and methine C(sp3 )-H bonds in alkyl ethers has little
influence on the regioselectivity. Selective difluoromethylthiolation of C-O
bonds has also been achieved. This represents not only an important step forward
in trifluoromethylthiolation but also a promising means for site-selective C-O
bond functionalization of unsymmetrical tertiary alkyl ethers.
PMID- 29952054
TI - An Immobilized-Dirhodium Hollow-Fiber Flow Reactor for Scalable and Sustainable C
H Functionalization in Continuous Flow.
AB - A scalable flow reactor is demonstrated for enantioselective and regioselective
rhodium carbene reactions (cyclopropanation and C-H functionalization) by
developing cascade reaction methods employing a microfluidic flow reactor system
containing immobilized dirhodium catalysts in conjunction with the flow synthesis
of diazo compounds. This allows the utilization of the energetic diazo compounds
in a safe manner and the recycling of the dirhodium catalysts multiple times.
This approach is amenable to application in a bulk-scale synthesis employing
asymmetric C-H functionalization by stacking multiple fibers in one reactor
module. The products from this sequential flow-flow reactor are compared with a
conventional batch reactor or flow-batch reactor in terms of yield,
regioselectivity, and enantioselectivity.
PMID- 29952055
TI - Dietary betaine improves meat quality and oxidative status of broilers under heat
stress.
AB - BACKGROUND: In order to investigate the effects of dietary betaine on meat
quality and oxidative status of broilers under heat stress (HS), a total of 144
Arbor Acres male broilers were randomly allocated to three groups with six
replicates of eight broilers per replicate from 21 to 42 days of age. The
broilers in the control group were raised at 22 degrees C and received a basal
diet, and the broilers in the other two groups were raised at 34 degrees C from
9:00 to 17:00 and at 22 degrees C for the rest of the time and fed a basal diet
with or without 1000 mg kg-1 betaine. RESULTS: Dietary betaine supplementation
tended (P < 0.1) to reverse the decreased body weight gain and feed intake of
broilers induced by HS. The decreased redness (a* value) of breast muscle in
broilers under HS was restored (P < 0.05) by betaine, which tended (P < 0.1) to
decrease drip loss of breast muscle. The broilers fed betaine-supplemented diets
had a tendency (P < 0.1) to increase moisture content but decrease crude protein
content of breast muscle in broilers under HS. Moreover, betaine resulted in
higher (P < 0.05) glutathione content and activities of superoxide dismutase and
glutathione peroxidase but lower (P < 0.05) malondialdehyde content in breast
muscle of broilers exposed to HS. CONCLUSION: Dietary betaine supplementation
alleviated the negative effects of HS on some traits of meat quality and
oxidative status of broilers. (c) 2018 Society of Chemical Industry.
PMID- 29952056
TI - Versatile Micropatterns of N-Heterocyclic Carbenes on Gold Surfaces: Increased
Thermal and Pattern Stability with Enhanced Conductivity.
AB - Patterned monolayers of N-heterocyclic carbenes (NHCs) on gold surfaces were
obtained by microcontact printing of NHC-CO2 adducts and NHC(H)[HCO3 ] salts. The
NHC-modified areas showed an increased conductivity compared to unmodified gold
surface areas. Furthermore, the remaining surface areas could be modified with a
second, azide-functionalized carbene, facilitating further applications and post
printing modifications. Thorough elucidation by a variety of analytical methods
offers comprehensive evidence for the viability of the methodology reported here.
The protocol enables facile access to versatile, microstructured NHC-modified
gold surfaces with highly stable patterns, enhanced conductivity, and the option
for further modification.
PMID- 29952057
TI - Early post-operative diet upgrade in older patients may improve energy and
protein intake but patients still eat poorly: an observational pilot study.
AB - BACKGROUND: Malnutrition is prevalent across acute care facilities, particularly
in older patients, and contributes to poor surgical outcomes. Clinical practice
guidelines recommend the early reintroduction of a full oral diet post
operatively. The present study aimed to compare estimated energy (EEI) and
protein (EPI) intake of patients who received early diet upgrade with those who
did not. METHODS: Patients >=65 years admitted post-operatively to general
surgical wards were included. EEI and EPI were calculated and dichotomised as
meeting >=50% or <50% estimated energy (EER) and protein (EPR) requirements. Mean
intake and proportion of patients meeting <50% estimated requirements were
compared between those who received early upgrade and those who did not at post
operative day (POD)2. RESULTS: Thirty-four patients [mean (SD) age 72.9 (5.7)
years, 59% male] were analysed at POD2 [EEI: mean 4.2 (2.6) MJ day-1 , 56% (n =
19) met >=50% EER; EPI: mean 38.7 (29.5) g day-1 , 26% (n = 9) met >=50% EPR].
The majority (n = 25, 74%) were upgraded to a nonfluid diet by POD2. More
patients on fluid diets consumed <50% EER (P = 0.025) and <50% EPR (P = 0.073).
No patient on a fluid diet met >=50% of EPR. CONCLUSIONS: Although the majority
of older patients received early diet upgrade and these patients consumed more
energy and protein than those on fluid diets, as a whole, older patients ate
poorly post-operatively. Fluid diets should therefore not be used
indiscriminately and other approaches to improve post-operative intake of older
patients, such as fortified diets, oral nutritional supplements and meal
environment interventions, should be adopted.
PMID- 29952058
TI - I had a dream....
PMID- 29952059
TI - Repeat Module-Based Rational Design of a Photoswitchable Protein for Light-Driven
Control of Biological Processes.
AB - Light-driven control of biological processes using photoswitchable proteins
allows high spatiotemporal interrogation or manipulation of such processes,
assisting in understanding their functions. Despite considerable advances,
however, the wide spread use of optical control has been hampered by a limited
repertoire of photoswitchable proteins and a lack of generalized design strategy.
Herein, we present a repeat module-based rational design of a photoswitchable
protein composed of LRR (Leucine-rich repeat) modules using azobenzene as a
photochromic ligand. Our design approach involves the rational selection of a
Cbeta pair between two nearby modules within a convex region and subsequent cross
linking with a photochromic ligand. We demonstrate the general utility and
potential of our strategy by showing the design of three target-specific
photoswitchable proteins and a light-driven modulation of the cell signaling.
With an abundance of LRR proteins in nature, our approach can expand the
repertoire of photoswitchable proteins for light-driven control of biological
processes.
PMID- 29952060
TI - Photonics and Optoelectronics of 2D Metal-Halide Perovskites.
AB - In the growing list of 2D semiconductors as potential successors to silicon in
future devices, metal-halide perovskites have recently joined the family. Unlike
other conversional 2D covalent semiconductors such as graphene, transition metal
dichalcogenides, black phosphorus, etc., 2D perovskites are ionic materials,
affording many distinct properties of their own, including high photoluminescence
quantum efficiency, balanced large exciton binding energy and oscillator
strength, and long carrier diffusion length. These unique properties make 2D
perovskites potential candidates for optoelectronic and photonic devices such as
solar cells, light-emitting diodes, photodetectors, nanolasers, waveguides,
modulators, and so on, which represent a relatively new but exciting and rapidly
expanding area of research. In this Review, the recent advances in emerging 2D
metal-halide perovskites and their applications in the fields of optoelectronics
and photonics are summarized and insights into the future direction of these
fields are offered.
PMID- 29952061
TI - Nanoparticles for Detection and Treatment of Peripheral Arterial Disease.
AB - Peripheral arterial disease (PAD) is defined as a slow, progressive disorder of
the lower extremity arterial vessels characterized by chronic narrowing that
often results in occlusion and is associated with loss of functional capacity.
Although the PAD occurrence rate is increasing in the elderly population,
outcomes with current treatment strategies are suboptimal. Hence, there is an
urgent need to develop new technologies that overcome limitations of traditional
modalities for PAD detection and therapy. In this Review, the application of
nanotechnology as a tool that bridges the gap in PAD diagnosis and therapy is in
focus. Several materials including synthetic, natural, biodegradable, and
biocompatible materials are used to develop nanoparticles for PAD diagnostic
and/or therapeutic applications. Moreover, various recent research approaches are
being explored to diagnose PAD through multimodality imaging with different
nanoplatforms. Further efforts include targeted delivery of various therapeutic
agents using nanostructures as carriers to treat PAD. Last, but not least,
despite being a fairly new field, researchers are exploring the use of
nanotheranostics for PAD detection and therapy.
PMID- 29952062
TI - The Impact of Medicaid Managed Care Plan Type on Continuous Medicaid Enrollment:
A Natural Experiment.
AB - OBJECTIVE: To assess the impact of assignment to a Medicaid-focused versus mixed
managed care plan on continuity of Medicaid coverage. DATA SOURCES: 2011-2016
Medicaid claims from a Northeastern state. STUDY DESIGN: Following the exit of a
Medicaid managed care insurer, Medicaid administrators prioritized provider
networks in reassigning enrollees, but randomly assigned beneficiaries whose
providers were equally represented in the two plans. We leveraged the natural
experiment created by random plan assignment and conducted an instrumental
variable analysis. DATA COLLECTION: We analyzed Medicaid claims for 12,083
beneficiaries who were members of the exiting Blue Cross Blue Shield plan prior
to January 1, 2011. PRINCIPAL FINDINGS: Managed care plan type did not
significantly impact continuous enrollment in the Medicaid program. Greater
outpatient utilization and the presence of a special need among children were
associated with longer enrollment in Medicaid. CONCLUSIONS: Managed care plans
did not differ in their capacity to keep Medicaid beneficiaries continuously
enrolled in coverage, despite differences in plan features.
PMID- 29952063
TI - Authors' reply re: The incidence, characteristics, management and outcomes of
anaphylaxis in pregnancy: a population-based descriptive study.
PMID- 29952064
TI - Accuracy of the femoral tunnel position in robot-assisted anterior cruciate
ligament reconstruction using a magnetic resonance imaging-based navigation
system: A preliminary report.
AB - BACKGROUND: Tunnel misplacement is a common cause of failed anterior cruciate
ligament (ACL) reconstruction. In this study, the accuracy of the femoral tunnel
position was evaluated in robot-assisted ACL reconstruction using a magnetic
resonance imaging (MRI)-based navigation system. We hypothesized that a
difference of less than 2 mm between the planned femoral tunnel position and the
created one was achievable. METHODS: Four cadaveric knees underwent robot
assisted ACL reconstruction. A 3-dimensional model using pre-operative MRI images
was used for preoperative planning, and a computed tomography (CT) scan was
performed postoperatively. The planned and the created femoral tunnels were
compared to assess the accuracy of the femoral tunnel position. RESULTS: The
distance between the intra-articular points of the planned and the created
tunnels was 7.78 mm in the first experiment and 1.47 mm in the last one. The
difference in tunnel length was 4.62 mm in the first experiment and 0.99 mm in
the last one. CONCLUSIONS: Accuracy of the femoral tunnel position improved with
each robot-assisted ACL reconstruction using an MRI-based navigation system. In
the last experiment, the accuracy of the femoral tunnel position was
satisfactory.
PMID- 29952065
TI - Single Nanoparticle Magnetic Spin Memristor.
AB - There is an increasing demand for the development of a simple Si-based universal
memory device at the nanoscale that operates at high frequencies. Spin
electronics (spintronics) can, in principle, increase the efficiency of devices
and allow them to operate at high frequencies. A primary challenge for reducing
the dimensions of spintronic devices is the requirement for high spin currents.
To overcome this problem, a new approach is presented that uses helical chiral
molecules exhibiting spin-selective electron transport, which is called the
chiral-induced spin selectivity (CISS) effect. Using the CISS effect, the active
memory device is miniaturized for the first time from the micrometer scale to 30
nm in size, and this device presents memristor-like nonlinear logic operation at
low voltages under ambient conditions and room temperature. A single
nanoparticle, along with Au contacts and chiral molecules, is sufficient to
function as a memory device. A single ferromagnetic nanoplatelet is used as a
fixed hard magnet combined with Au contacts in which the gold contacts act as
soft magnets due to the adsorbed chiral molecules.
PMID- 29952066
TI - Cross-polarization reflectance imaging of root caries and dental calculus on
extracted teeth at wavelengths from 400 to 2350 nm.
AB - The identification of root caries and calculus on tooth roots is of increasing
importance with our aging population. Exposed root surfaces are often impacted by
erosion, abrasion, calculus and staining which can make the identification and
management of caries challenging. Identification of dental calculus on root
surfaces and verification of its removal is also important for patient education
and to decrease susceptibility to caries and periodontal disease. The objective
of this study was to determine how the contrast of root caries lesions and dental
calculus varies with wavelength in the visible to near-infrared. The contrast of
suspected root caries lesions and dental calculus on 30 extracted teeth was
measured using cross-polarization reflectance measurements at wavelengths from
400 to 2350 nm. Significantly higher (P < 0.05) lesion contrast was measured at
wavelengths greater than 1460 nm. Stains interfered significantly at wavelengths
less than 850 nm yielding non-diagnostic contrast for root caries lesions. We
postulate that the high absorption of water at longer wavelengths reduced the
light scattering from the surrounding and underlying normal dentin, thus
increasing the lesion contrast. This study indicates that wavelengths beyond 1400
nm are advantageous for imaging calculus and caries lesions on root surfaces due
to the high contrast and lack of interference from stain.
PMID- 29952067
TI - Localized lymphoid hyperplasia of the spleen mimicking metastatic colorectal
adenocarcinoma.
PMID- 29952068
TI - Evaluation of neonicotinoid insecticides for oestrogenic, thyroidogenic and
adipogenic activity reveals imidacloprid causes lipid accumulation.
AB - Few studies have investigated non-target effects of neonicotinoid insecticides on
mammalian physiology. This is largely due to the widespread perception that their
weak affinity for nicotinic acetylcholine receptor subtypes in vertebrates makes
mammalian exposures unlikely to pose health risks. To the best of our knowledge,
we describe the first investigation evaluating the interaction of seven principal
neonicotinoid insecticides (thiamethoxam, imidacloprid, clothianidin,
flupyradifurone, dinotefuran, nitenpyram, thiacloprid) with oestrogen and thyroid
hormone receptors, as well as their adipogenic effects, in mammalian cell culture
assay systems. An E-Screen with MCF-7 and T-Screen with GH3 cells respectively
showed a lack of oestrogen and thyroid hormone receptor agonist effects for any
of the neonicotinoids tested. Adipogenicity was assessed by the ability to
stimulate lipid accumulation in adipocyte differentiated 3T3-L1 cells, with only
imidacloprid scoring positive in this assay causing triglyceride accumulation
from a concentration of 50 mg l-1 . Data mining of ToxCast high-throughput
screening assays revealed that this adipogenic effect of imidacloprid is probably
mediated via the pregnane X receptor.
PMID- 29952069
TI - The effects of a windborne pollen-provisioning cover crop on the phytoseiid
community in citrus orchards in Israel.
AB - BACKGROUND: Several phytoseiid species can potentially control the citrus rust
mite (CRM). Their effectiveness varies, however, as do their intraguild
interactions. Under laboratory conditions, Euseius stipulatus, E. scutalis and
Iphiseius degenerans preyed effectively on CRM, whereas Amblyseius swirskii and
Typhlodromus athiasae had no effect on CRM. In combination with A. swirskii,
Euseius numbers were reduced due to intraguild predation, and consequently CRM
suppression was less effective. In the field, predatory mite species can be
variably provisioned by windborne pollen released from cover crops such as Rhodes
grass (RG). We aimed to determine the effects of RG on the phytoseiid community
in two field experiments, on different cultivars (pomelo and Shamouti orange). We
also tested these communities for negative interspecific abundance relationships
that are expected if their respective laboratory-observed intraguild interactions
are manifested in the field. RESULTS: Overall, on pomelo, we observed a dominance
of A. swirskii, relatively low E. stipulatus and high CRM abundances. Amblyseius
swirskii and E. stipulatus abundances were both elevated near RG, despite
apparent intraguild predation by A. swirskii. Conversely, T. athiasae abundances
were lower near RG, likely due to predation by A. swirskii. On Shamouti, E.
stipulatus abundances were much higher than on pomelo and were not negatively
related to A. swirskii abundances. There, RG increased E. stipulatus abundance,
and CRM was reduced. CONCLUSION: RG cover cropping can enhance CRM control,
depending on variation in intraguild interactions among phytoseiids, particularly
between A. swirskii and E. stipulatus. These may be modulated by climatic and/or
cultivar effects. (c) 2018 Society of Chemical Industry.
PMID- 29952070
TI - Multifunctional Electrospun Nanofibers for Enhancing Localized Cancer Treatment.
AB - Localized cancer treatment is one of the most effective strategies in clinical
destruction of solid tumors at early stages as it can minimize the side effects
of cancer therapeutics. Electrospun nanofibers have been demonstrated as a
promising implantable platform in localized cancer treatment, enabling the on
site delivery of therapeutic components and minimizing side effects to normal
tissues. This Review discusses the recent cutting-edge research with regard to
electrospun nanofibers used for various therapeutic approaches, including gene
therapy, chemotherapy, photodynamic therapy, thermal therapy, and combination
therapy, in enhancing localized cancer treatment. Furthermore, it extensively
analyzes the current challenges and potential breakthroughs in utilizing this
novel platform for clinical transition in localized cancer treatment.
PMID- 29952071
TI - Enhancing vascular visualization in laser speckle contrast imaging of blood flow
using multi-focus image fusion.
AB - Laser speckle contrast imaging (LSCI) is a full-field optical imaging method for
monitoring blood flow and vascular morphology with high spatiotemporal
resolution. However, due to the limited depth of field of optical system, it is
difficult to capture a clear blood flow image with all blood vessels focused,
especially for the non-planar biological tissues. In this paper, a multi-focus
image fusion method based on contourlet transform is introduced to reduce the
misfocus effects in LSCI. The experimental results suggest that this method can
provide an all-in-focus blood flow image, which is convenient to observe the
blood vessels. This article is protected by copyright. All rights reserved.
PMID- 29952072
TI - Embracing the wild profusion: A Foucauldian analysis of the impact of healthcare
standardization on nursing knowledge and practice.
AB - Standardization has emerged as the dominant principle guiding the organization
and provision of healthcare, with standards resultantly shaping how nurses
conceptualize and deliver patient care. Standardization has been critiqued as
homogenizing diverse patient experiences and diminishing nurses' skills and
critical thinking; however, there has been limited examination of the
philosophical implications of standardization for nursing knowledge and practice.
In this manuscript, I draw on Foucault's philosophy of order and categorization
to inform an analysis of the consequences of healthcare standardization for the
profession of nursing. I utilize three exemplars to illustrate the impact of the
primacy of standardized thinking and practices on nurses, patients and families:
pain assessments using the 0-10 pain scale; patient triage emergency departments
through the Canadian Triage and Acuity Scale; and determination of cause of death
within the context of the current opioid crisis. Through each exemplar, I
demonstrate that standardization reductively constrains nursing knowledge and the
health and healthcare experiences of patients and populations. I argue that the
centrality of standardization must be re-envisioned to embrace the complexity of
health and more effectively and meaningfully frame nursing knowledge and practice
within healthcare systems.
PMID- 29952073
TI - Birth weight and social determinants in diabetes and hypertension.
PMID- 29952074
TI - Antimicrobial blue light photoinactivation of Pseudomonas aeruginosa: Quorum
sensing signaling molecules, biofilm formation and pathogenicity.
AB - Pseudomonas aeruginosa is a common causative bacterium of acute and chronic
infections that have been responsible for high mortality over the past decade. P.
aeruginosa produces many virulence factors such as toxins, enzymes and dyes that
are strongly dependent on quorum sensing (QS) signaling systems. P. aeruginosa
has three major QS systems (las, rhl and Pseudomonas quinolone signal) that
regulate the expression of genes encoding virulence factors as well as biofilm
production and maturation. Antimicrobial blue light (aBL) is considered a
therapeutic option for bacterial infections and has other benefits, such as
reducing bacterial virulence. Therefore, this study investigated the efficacy of
aBL to reduce P. aeruginosa pathogenicity. aBL treatment resulted in the reduced
activity of certain QS signaling molecules in P. aeruginosa and inhibited biofilm
formation. in vivo tests using a Caenorhabditis elegans infection model indicated
that sublethal aBL decreased the pathogenicity of P. aeruginosa. aBL may be a new
virulence-targeting therapeutic approach.
PMID- 29952075
TI - Photothermal therapy enhanced the effectiveness of imiquimod against refractory
cutaneous warts through boosting immune responses.
AB - Refractory cutaneous warts are difficult to eliminate. In situ photo
immunotherapy (ISPI) is an innovative treatment concept combining local
photothermal therapy (PTT) and topical immunotherapy using imiquimod. To compare
the efficacy of ISPI vs topical imiquimod alone, a prospective randomized
controlled trial was performed with patients suffering from refractory cutaneous
warts. In both groups, approximately 50% of the skin surface containing warts was
treated for 6 weeks. On the basis of topical imiquimod, ISPI includes an
additional 808 nm laser irradiation. Treatment response, temperatures during
irradiation and histopathologic examination were evaluated. The complete response
rate in the ISPI-group (22/36, 61.1%) was significantly higher than in the
imiquimod alone group (11/34, 32.4%). In the ISPI-group, the mean maximum
temperature was 44.5 +/- 5.1 degrees C, and obvious lymphocytic infiltration was
found in the perivasculature of the dermis. There was no recurrence or worsening
in both groups during the 12-month follow-up. No obvious adverse reaction was
observed. This study demonstrates that ISPI can be used as an effective and safe
treatment modality for refractory cutaneous warts.
PMID- 29952076
TI - International nurses to the rescue: The role and contribution of the nurses of
the International Brigades during the Spanish Civil War.
AB - AIM: To describe the life and work of the international nurses of the
International Brigades during the Spanish Civil War and to examine their role in
relation to their contribution to Spanish nursing in this period. METHODS: This
historical study is based primarily on the memoirs of the international nurses
who joined the war health services of the International Brigades during the
Spanish Civil War. The evidence that was elicited from these sources was compared
and contrasted with other contemporary documents in order to compare their
perspectives with those of other contemporaries. RESULTS: The nurses of the
International Brigades joined the front line health services as part of the
mobile medical and surgical teams that were attached to the fighting units. They
lived and worked under extreme conditions, often under fire. Their work while in
Spain was not limited to care delivery but also included managerial and
educational aspects. The international nurses' observations of Spanish nursing at
the time were not always accurate, which might be explained by a lack of contact
with qualified Spanish nursing staff due to a shortage of fully qualified nurses.
CONCLUSION: In the absence of the voices of the Spanish nurses themselves, the
written records of the international nurses were invaluable in analyzing Spanish
nursing in this period. Their testimonies are, in essence, the international
nurses' legacy to the Spanish nurses who stayed behind after the departure of the
International Brigadists in 1938.
PMID- 29952077
TI - Circulating miR-338-5p is a potential diagnostic biomarker in colorectal cancer.
AB - OBJECTIVE: The expression of miR-338-5p has been reported to be upregulated in
colorectal cancer (CRC) tissues. Clinicopathological features indicate that miR
338-5p overexpression correlates with the metastatic status of CRC. This study
was aimed to investigate the diagnostic value of serum miR-338-5p for CRC.
METHODS: Peripheral blood samples were collected from 210 participants, including
80 patients with CRC, 50 with colorectal polyps and 80 healthy controls. Serum
miR-338-5p was quantified by quantitative reverse-transcription polymerase chain
reaction. The area under the receiver operating characteristic curve (AUROC) was
used to estimate the diagnostic value of miR-338-5p, carcinoembryonic antigen
(CEA) and the combination of these two biomarkers. RESULTS: Serum miR-338-5p
levels (fold change) in patients with CRC and colorectal polyps, and controls
were 4.94 +/- 1.13, 4.12 +/- 0.75 and 3.07 +/- 0.75, respectively. Significant
differences were observed between the groups (P < 0.001). The AUROC of miR-338-5p
was 0.923 (95% CI 0.882-0.964) and 0.845 (95% CI 0.792-0.898), respectively, for
distinguishing CRC from healthy controls or from those without CRC. The AUROC of
the combination of miR-338-5p and CEA was 0.932 (95% CI 0.882-0.964), with a
sensitivity of 85%, a specificity of 88.8% at a cut-off value of 8.16.
CONCLUSIONS: Circulating miR-338-5p may serve as a potential noninvasive
diagnostic biomarker for detecting CRC. The combination of miR-338-5p and CEA
exhibits the highest diagnostic value in our study.
PMID- 29952078
TI - Unidimensionality of the personality inventory for DSM-5 facets: Evidence from
two Czech-speaking samples.
AB - To date, numerous studies have confirmed empirical relevance of the personality
trait model defined in the Alternative DSM-5 Model for Personality Disorders. The
supposed single-factor structure of its facets and general domains across various
samples, however, has not been researched thoroughly. This study focused on
evaluating the hypothesized unidimensional factor structure of the lower-order
personality trait facets, as well as the validity of the higher-order domains.
The Czech version of the Personality Inventory for DSM-5 (PID-5) was used in a
sample of 351 community volunteers and 143 psychiatric patients. The fit of the
model for 25 facets could not be replicated with the original PID-5, while a
shortened version confirmed the single-factor structure of all facets and their
relevance to the five proposed domains. The findings support unidimensional
structure of the modified DSM-5 personality trait model and imply discussion of
the utility of the proposed PID-5 version. Copyright (c) 2018 John Wiley & Sons,
Ltd.
PMID- 29952079
TI - Extraction of Cell-Free Whole Blood Plasma Using a Dielectrophoresis-Based
Microfluidic Device.
AB - Blood is the most valuable and convenient source of disease diagnostic
biomarkers, but plasma must be extracted from blood prior to further biomarker
detection and analysis. Traditional plasma extraction methods depend greatly on
benchtop equipment and are often cumbersome, time-consuming, and unsuitable for
point-of-care (POC) applications. On the other hand, highly diluted blood plasma
extraction methods potentially introduce greater test result uncertainty and
lower detection sensitivity. Because simpler integrated and more efficient plasma
extraction methods that avoid sample dilution are highly desired, the authors
develop a simple dielectrophoresis (DEP)-based microfluidic device for plasma
extraction from whole blood. The separation strategy is straightforward and the
device is easy to manufacture, due to its lack of mechanistic complexity. Human
plasma is extracted from whole blood without dilution or other complex pre
handling steps and attained purity approaching 100%, with a calculated plasma
yield of ~31%. In addition, flow rate and voltage effects on extraction
efficiency are also evaluated. This work provides a simple, integrated, non
invasive, continuous, and efficient method for plasma extraction without dilution
using a lab-on-chip platform with potential application for real-time biomarker
detection from blood.
PMID- 29952080
TI - The impact of brain-derived neurotrophic factor Val66Met polymorphism on
cognition and functional brain networks in patients with intractable partial
epilepsy.
AB - INTRODUCTION: Medial temporal lobe epilepsy (mTLE) is the most common refractory
focal epilepsy in adults. Around 30%-40% of patients have prominent memory
impairment and experience significant postoperative memory and language decline
after surgical treatment. BDNF Val66Met polymorphism has also been associated
with cognition and variability in structural and functional hippocampal indices
in healthy controls and some patient groups. AIMS: We examined whether BDNF
Val66Met variation was associated with cognitive impairment in mTLE. METHODS: In
this study, we investigated the association of Val66Met polymorphism with
cognitive performance (n = 276), postoperative cognitive change (n = 126) and
fMRI activation patterns during memory encoding and language paradigms in 2
groups of patients with mTLE (n = 37 and 34). RESULTS: mTLE patients carrying the
Met allele performed more poorly on memory tasks and showed reduced medial
temporal lobe activation and reduced task-related deactivations within the
default mode networks in both the fMRI memory and language tasks than Val/Val
patients. CONCLUSIONS: Although cognitive impairment in epilepsy is the result of
a complex interaction of factors, our results suggest a role of genetic factors
on cognitive impairment in mTLE.
PMID- 29952081
TI - Nanobiopolymers Fabrication and Their Life Cycle Assessments.
AB - Living organisms produced nanopolymers (nanobiopolymers for short), such as
nanocellulose, nanochitin, nanosilk, nanostarch, and microbial nanobiopolymers,
having received widely scientific and engineering interests in recent years.
Compare with petroleum-based polymers, biopolymers are sustainable and
biodegradable. The unique structural features that stem from nanosized effects,
such as ultrahigh aspect ratio and length-diameter ratio, further endow
nanobiopolymers with high transparence and versatile processability. To fabricate
these nanobiopolymers, a variety of mechanical, chemical, and synthetic biology
techniques have been developed. The applications of the isolated nanobiopolymers
have been extended from polymer fillers into wide emerging high-tech fields, such
as biomedical devices, bioplastics, display panels, ultrafiltration membranes,
energy storage devices, and catalytic supports. Accordingly, in the review, the
authors first introduce isolation techniques to fabricate nanocellulose,
nanochitin, nanosilk, and nanostarch. Then, the authors summarized the
nanobiopolymers produced from biosynthetic pathway, including microbial
polyamides, polysaccharides, and polyesters. On the other hand, most of these
techniques require high energy consumption and usage of chemical reagents. In
this regard, life cycle assessment offered a quantitative route to precisely
evaluate and compare environmental benefits of different artificial isolation
approaches, which are also summarized in the second section of the review.
PMID- 29952082
TI - The potato transcription factor StbZIP61 regulates dynamic biosynthesis of
salicylic acid in defense against Phytophthora infestans infection.
AB - Salicylic acid (SA) signalling plays an essential role in plant innate immunity.
In this study, we identified a component in the SA signaling pathway in potato
(Solanum tuberosum), the transcription factor StbZIP61, and characterized its
function in defence against Phytophthora infestans. Expression of StbZIP61 was
induced upon P. infestans infection and following exposure to the defense
signaling hormones SA, ethylene and jasmonic acid. Overexpression of StbZIP61
increased the tolerance of potato plants to P. infestans while RNA interference
(RNAi) increased susceptibility. Yeast two-hybrid and pull down experiments
revealed that StbZIP61 could interact with an NPR3-like protein (StNPR3L) that
inhibited its DNA-binding and transcriptional activation activities. Moreover,
StNPR3L interacted with StbZIP61 in an SA-dependent manner. Among candidate genes
involved in SA-regulated defense responses, StbZIP61 had a significant impact on
expression of StICS1, which encodes a key enzyme for SA biosynthesis. StICS1
transcription was induced upon P. infestans infection and this responsive
expression to the pathogen was reduced in StbZIP61 RNAi plants. Accordingly,
StICS1 expression was remarkably enhanced in StbZIP61-overexpressing plants.
Together, our data demonstrate that StbZIP61 functions in concert with StNPR3L to
regulate the temporal activation of SA biosynthesis, which contributes to SA
mediated immunity against P. infestans infection in potato.
PMID- 29952083
TI - The efficiency of light-emitting diode suction traps for the collection of South
African livestock-associated Culicoides species.
AB - Culicoides biting midges (Diptera: Ceratopogonidae) are vectors of a range of
orbiviruses that cause important veterinary diseases such as bluetongue and
African horse sickness. The effective monitoring of Culicoides species diversity
and abundance, both at livestock and near potential wildlife hosts, is essential
for risk management. The Onderstepoort 220-V ultraviolet (UV) light trap is
extensively used for this purpose. Reducing its power requirements by fitting low
energy light-emitting diodes (LEDs) can lead to greater flexibility in
monitoring. A comparison of the efficiency of the 220-V Onderstepoort trap (8-W
fluorescent UV light) with the efficiency of the 220-V or 12-V Onderstepoort
traps fitted with red, white, blue or green LEDs or a 12-V fluorescent
Onderstepoort trap demonstrated the 220-V Onderstepoort trap to be the most
efficient. All the results showed nulliparous Culicoides imicola Kieffer females
to be the dominant grouping. Despite the lower numbers collected, 12-V traps can
be used in field situations to determine the most abundant species.
PMID- 29952085
TI - Identification of pyrazolopyridine derivatives as novel spleen tyrosine kinase
inhibitors.
AB - Inhibition of spleen tyrosine kinase (Syk) is a promising strategy for the
treatment of various allergic and autoimmune disorders such as asthma, rheumatoid
arthritis, and allergic rhinitis. Previously, a Syk inhibitor with novel indazole
scaffold was discovered by structure-based virtual screening. Herein, the
structure-activity relationship of the indazole Syk inhibitors was investigated.
Several new inhibitors demonstrated potent activity against Syk. In particular,
compound 18c showed good Syk inhibitory activity (IC50 = 1.2 uM), representing a
good lead compound for further optimization.
PMID- 29952084
TI - Identification of new diagnostic biomarkers for Mycobacterium tuberculosis and
the potential application in the serodiagnosis of human tuberculosis.
AB - Mycobacterium tuberculosis (M. tuberculosis) regions of difference (RD) encode
proteins which are potentially useful as diagnostic reagents for tuberculosis
(TB). In this study, 75 genes from M. tuberculosis RD1-RD16 were successfully
cloned from which 68 proteins were expressed and purified. Three serum pools from
patients with pulmonary TB (PTB), extra-pulmonary tuberculosis (EPTB) and healthy
controls (HC) were used to preliminarily screen individual RD proteins. The OD630
ratio of the PTB or EPTB to the HC group >= 2-fold was positive. As a result, 29
proteins were obtained. The serological response to the identified antigens was
further verified using 58 PTB samples with 38 sera from smear-positive PTB (PTB
SP) patients and 20 sera from smear-negative PTB (PTB-SN) patients, 16 EPTB
samples, 42 latent M. tuberculosis infection samples and 40 HCs by indirect
ELISA. With respect to the PTB diagnosis, receiver operating characteristic
analysis showed that Rv0222 [area under the curve (AUC), 0.8129; 95% confidence
interval (CI), 0.7280-0.8979] and Rv3403c (AUC, 0.8537; 95% CI, 0.7779-0.9294)
performed better than ESAT6/CFP10 (AUC, 0.7435; 95% CI, 0.6465-0.8406). Rv0222
and Rv3403c demonstrated the highest diagnostic ability in the PTB-SP group
(sensitivity, 86.8%; specificity, 80%), while Rv3403c demonstrated the highest
diagnostic ability in the PTB-SN group (sensitivity, 70%; specificity, 80%). With
respect to the EPTB diagnosis, Rv0222 exhibited the highest diagnostic value
(AUC, 0.7523; sensitivity, 68.8%; specificity, 87.5%). In addition, the
combination of Rv0222 and Rv3403c improved the test for PTB-SN. These results
indicate that Rv0222 and Rv3403c would be potential diagnostic biomarkers for
active TB serodiagnosis. Mouse experiments demonstrated that Rv0222 and Rv3403c
elicited specific cellular and humoral responses which were characterized by
production of IFN-gamma, IgG1, and IgG2a, but a higher level of IgG1 than IgG2a.
PMID- 29952086
TI - Prognostic value of the number of negative lymph nodes in esophageal carcinoma
without lymphatic metastasis.
AB - BACKGROUND: The impact of the number of negative lymph nodes (LNs) on survival in
patients with esophageal cancer remains a controversial issue. This study
investigated the association between the number of resected LNs and the prognosis
of patients with node-negative esophageal carcinoma. METHODS: A retrospective
review was performed of the data of 429 patients who underwent esophagectomy with
modern two-field lymphadenectomy for the treatment of esophageal cancer between
January 1998 and December 2008. Histopathology showed no LN involvement in the
patient sample. The prognostic impact of the number of negative LNs and the
clinicopathological factors were analyzed. RESULTS: The overall median survival
time and the one, three, and five-year overall survival rates were 63.0 months
and 78.5%, 64.0%, and 51.2%, respectively. Survival analysis confirmed that the
number of negative LNs and the depth of tumor invasion were independent
prognostic factors. Patients with a high number of negative LNs had a better
overall survival rate than patients with a low number of negative LNs (P <
0.001). Patients with dissected LNs > 14 for pT1 tumors (P < 0.001) and > 19 for
pT2-3 tumors (P < 0.001 and P = 0.001, respectively) had better long-term
survival outcomes. CONCLUSIONS: The number of negative LNs is an independent
prognostic factor for node-negative esophageal carcinoma. Extended LN dissection
is recommended to improve the survival of patients with node-negative esophageal
carcinoma.
PMID- 29952087
TI - Synthesis of N,O,B-Chelated Dipyrromethenes through an Unexpected Intramolecular
Cyclisation: Enhanced Near-Infrared Emission in the Aggregate/Solid State.
AB - The first example of the synthesis of mono-N,O-B-chelated dipyrromethene (BODIPY)
derivatives through an unexpected intramolecular nucleophilic displacement of the
fluorine by alkenols in the presence of boron trifluoride as Lewis acid is
reported. The chlorine in the indacene core allowed for further structural
modifications through nucleophilic substitutions or palladium-catalysed coupling
reactions to afford new fluorophores with tuneable photophysical properties.
Their expanded conjugation structure resulted in distinct red-shifted absorption
and emission spectra in organic solutions. Furthermore, the twisted steric
hindrance of the benzene substitution patterns suppressed aggregation-induced
quenching, leading to an enhanced NIR emission in the aggregate/solid state,
which was rarely observed for BODIPY dyes. Nanoparticles of the fluorophores
formed by the assembly with the polymeric surfactant F127 were successfully used
for bioimaging of living cells and for tumour-targeted imaging in a tumour
bearing mouse model.
PMID- 29952088
TI - Smaller hippocampal volume following sexual assault in women is associated with
post-traumatic stress disorder.
AB - OBJECTIVE: Exposure to sexual assault is a significant risk factor to develop
post-traumatic stress disorder (PTSD) in females. The early neurobiological
changes leading to the development of PTSD remain understudied and unclear in
this population. METHODS: Participants were 27 adult females recruited within a
month following exposure to sexual assault (T1) and 20 age-matched non-exposed
controls. Among the victims, 10 participants met (PTSD+) and 15 did not meet
(PTSD-) DSM-IV criteria for PTSD 6 months post-trauma (T2). At both visits,
hippocampal and amygdala volumes were extracted from magnetic resonance imaging
scans, and indices of total diurnal cortisol changes were derived from individual
areas under the curve relative to the ground (AUCg). Measures at T1 were compared
between groups at T1, measures at T2 between groups at T2, and measures at T1
between groups at T2. RESULTS: At T1, victims had significantly smaller bilateral
hippocampal volumes, but not AUCg, than controls. At T2, neither hippocampal
volume nor AUCg significantly differed among the groups. However, the PTSD+ group
had significantly smaller hippocampal volumes at T1 than the control group, but
not compared to the PTSD- group. CONCLUSIONS: This study indicates that having
smaller hippocampal volumes is a risk factor to develop PTSD in females exposed
to sexual assault.
PMID- 29952089
TI - Numerous plasmacytoid dendritic cell infiltration in HIV-associated psoriasis
relieved only with antiretroviral therapy.
AB - The onset of psoriasis is often seen in HIV infection, called HIV-associated
psoriasis. Although HIV-associated psoriasis is usually refractory, there are
some cases relieved only by antiretroviral therapy. In those cases, the
pathogenesis may be formed differently from psoriasis vulgaris. We present the
case of a 42-year-old Japanese man with HIV-associated psoriasis. The patient
developed a systemic scaly eruption, especially on the soles. Histopathological
examination showed typical psoriatic findings and plasma cell infiltration into
the dermis. The eruption dramatically remitted with antiretroviral therapy alone,
without systemic treatment for psoriasis. In immunohistological findings, few
CD4+ cells were seen in the patient's skin. In addition, immunofluorescent
staining revealed more BDCA-2 and CD123 double-positive plasmacytoid dendritic
cell infiltration into the dermis than that of psoriasis vulgaris. We suggest
that the immune response to HIV including plasmacytoid dendritic cell
infiltration may involve in the development and remission of HIV-associated
psoriasis.
PMID- 29952090
TI - Which patients with heart failure should receive specialist palliative care?
AB - AIMS: We investigated which patients with heart failure (HF) should receive
specialist palliative care (SPC) by first creating a definition of need for SPC
in patients hospitalised with HF using patient-reported outcome measures (PROMs)
and then testing this definition using the outcome of days alive and out of
hospital (DAOH). We also evaluated which baseline variables predicted need for
SPC and whether those with this need received SPC. METHODS AND RESULTS: PROMs
assessing quality of life (QoL), symptoms, and mood were administered at baseline
and every 4 months. SPC need was defined as persistently severe impairment of any
PROM without improvement (or severe impairment immediately preceding death). We
then tested whether need for SPC, so defined, was reflected in DAOH, a measure
which combines length of stay, days of hospital re-admission, and days lost due
to death. Of 272 patients recruited, 74 (27%) met the definition of SPC needs.
These patients lived one third fewer DAOH than those without SPC need (and less
than a quarter of QoL-adjusted DAOH). A Kansas City Cardiomyopathy Questionnaire
(KCCQ) summary score of <29 identified patients who subsequently had SPC needs
(area under receiver operating characteristic curve 0.78). Twenty-four per cent
of patients with SPC needs actually received SPC (n = 18). CONCLUSIONS: A quarter
of patients hospitalised with HF had a need for SPC and were identified by a low
KCCQ score on admission. Those with SPC need spent many fewer DAOH and their DAOH
were of significantly worse quality. Very few patients with SPC needs accessed
SPC services.
PMID- 29952092
TI - Monolithic Polymer Nanoridges with Programmable Wetting Transitions.
AB - This paper describes polymeric nanostructures with dynamically tunable wetting
properties. Centimeter-scale areas of monolithic nanoridges can be generated by
strain relief of thermoplastic polyolefin films with fluoropolymer skin layers.
Changing the amount of strain results in polyolefin ridges with aspect ratios
greater than four with controlled feature densities. Surface chemistry and
topography are demonstrated to be able to be tailored by SF6 -plasma etching to
access multiple wetting states: Wenzel, Cassie-Baxter, and Cassie-impregnating
states. Reversible transitions among the wetting states can be realized in a
programmable manner by cyclic stretching and reshrinking the patterned substrates
without delamination and cracking.
PMID- 29952091
TI - Effect of 8-week leucine supplementation and resistance exercise training on
muscle hypertrophy and satellite cell activation in rats.
AB - We investigated the effects of regular leucine intake and/or resistance exercise
training on skeletal muscle hypertrophy and satellite cell activity after the
administration of different doses of leucine. Ten-week-old Sprague-Dawley rats
were assigned to six groups (n = 7 per group): a control group (Con), two groups
receiving either 10% (0.135 g/kg.wt) (Leu10) or 50% (0.675 g/kg.wt) (Leu50)
leucine supplementation, and three exercise groups receiving 0% (Ex), 10%
(Leu10Ex), and 50% (Leu50Ex) leucine supplementation. The rats performed ladder
climbing exercises thrice per week for 8 weeks, and received leucine supplements
at the same time daily. Muscle phenotypes were assessed by immunohistochemistry.
MyoD, myogenin, and IGF1 protein levels were determined by western blot. The
Leu50Ex group displayed significantly higher numbers of positive embryonic myosin
fibers (0.35 +/- 0.08, 250%) and myonuclei (3.29 +/- 0.3, 118.7%) than all other
groups. And exercise training groups increased the cross-sectional area, the
number of satellite cells and protein expression of MyoD, myogenin, and IGF1alpha
relative to the Control group (P < 0.05). However, Only leucine supplementation
group did not increase skeletal muscle hypertrophy and satellite cell activity,
regardless of the dose (P > 0.05). Leucine intake accompanied by regular exercise
training may increase satellite cell activation in skeletal muscles, and improve
muscle quality more effectively than continuous leucine ingestion alone.
PMID- 29952093
TI - Planned and Unplanned Hospital Admissions and Their Relationship with Social
Factors: Findings from a National, Prospective Study of People Aged 76 Years or
Older.
AB - OBJECTIVE: To examine the relationship between social factors and planned and
unplanned hospital admissions among older people. DATA SOURCES/STUDY SETTING:
2011 data from the Swedish Panel Study of Living Conditions of the Oldest Old
(SWEOLD) and data from the Swedish National Patient Register until December 31,
2012. STUDY DESIGN: The study had a prospective design. Data were analyzed via
Cox proportional hazard regressions with variables entered as blocks (social
factors, sociodemographic and ability factors, health factors). DATA COLLECTION:
Data were collected via interviews with people aged 76+ (n = 931). PRINCIPAL
FINDINGS: Living in institutions was negatively associated with planned
admissions (hazard ratio (HR): 0.29; confidence interval (CI): 0.09-0.88), while
being in receipt of home help was positively associated with unplanned admissions
(HR: 1.57; CI: 1.15-2.14). Low levels of social contacts and social activity
predicted unplanned admissions in bivariate analyses only. Higher ability to deal
with public authorities was positively associated with planned admissions (HR:
1.77; CI: 1.13-2.78) and negatively associated with unplanned admissions,
although the latter association was only significant in the bivariate analysis.
CONCLUSIONS: Hospital admissions are not only due to health problems but are also
influenced by the social care situation and by the ability to deal with public
authorities.
PMID- 29952094
TI - Sex differences influence intestinal epithelial stem cell proliferation
independent of obesity.
AB - The intestinal epithelium is continuously regenerated by cell renewal of
intestinal epithelial stem cells (IESCs) located in the intestinal crypts.
Obesity affects this process and results in changes in the size and cellular make
up of the tissue, but it remains unknown if there are sex differences in obesity
induced alterations in IESC proliferation and differentiation. We fed male and
female mice a 60% high-fat diet (HFD) or a 10% low-fat diet (LFD) for 3 months
and investigated the differences in (1) the expression of markers of different
intestinal epithelial cell types in vivo, and (2) lasting effects on IESC growth
in vitro. We found that the growth of IESCs in vitro were enhanced in females
compared with males. HFD induced similar in vivo changes and in vitro early
growth of IESCs in males and females. The IESCs isolated and grown in vitro from
females, though, showed an enhanced growth that was independent of obesity. To
determine whether this effect was driven by sex steroid hormones, we used primary
intestinal crypts isolated from male and female mice and investigated the
differences in (1) the expression of steroid hormone receptors, and (2) cell
proliferation in response to steroid hormones. We found that estrogen receptor
alpha was expressed in crypts from both sexes, but estrogen had no effect on
proliferation in either sex. These results suggest that obesity similarly effects
IESCs in males and females, but IESCs in females have greater proliferation
ability than males, but this is not driven by a direct effect of sex steroid
hormones on IESCs or other crypt cells that provide essential niche support for
IESCs.
PMID- 29952095
TI - Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for
chronic heart failure with preserved ejection fraction.
AB - BACKGROUND: Beta-blockers and inhibitors of the renin-angiotensin aldosterone
system improve survival and reduce morbidity in people with heart failure with
reduced left ventricular ejection fraction. There is uncertainty whether these
treatments are beneficial for people with heart failure with preserved ejection
fraction and a comprehensive review of the evidence is required. OBJECTIVES: To
assess the effects of beta-blockers, angiotensin converting enzyme inhibitors,
angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and
mineralocorticoid receptor antagonists in people with heart failure with
preserved ejection fraction. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase
and two clinical trial registries on 25 July 2017 to identify eligible studies.
Reference lists from primary studies and review articles were checked for
additional studies. There were no language or date restrictions. SELECTION
CRITERIA: We included randomised controlled trials with a parallel group design
enrolling adult participants with heart failure with preserved ejection fraction,
defined by a left ventricular ejection fraction of greater than 40 percent. DATA
COLLECTION AND ANALYSIS: Two review authors independently selected studies for
inclusion and extracted data. The outcomes assessed included cardiovascular
mortality, heart failure hospitalisation, hyperkalaemia, all-cause mortality and
quality of life. Risk ratios (RR) and, where possible, hazard ratios (HR) were
calculated for dichotomous outcomes. For continuous data, mean difference (MD) or
standardised mean difference (SMD) were calculated. We contacted trialists where
neccessary to obtain missing data. MAIN RESULTS: 37 randomised controlled trials
(207 reports) were included across all comparisons with a total of 18,311
participants.Ten studies (3087 participants) investigating beta-blockers (BB)
were included. A pooled analysis indicated a reduction in cardiovascular
mortality (15% of participants in the intervention arm versus 19% in the control
arm; RR 0.78; 95% confidence interval (CI) 0.62 to 0.99; number needed to treat
to benefit (NNTB) 25; 1046 participants; 3 studies). However, the quality of
evidence was low and no effect on cardiovascular mortality was observed when the
analysis was limited to studies with a low risk of bias (RR 0.81; 95% CI 0.50 to
1.29; 643 participants; 1 study). There was no effect on all-cause mortality,
heart failure hospitalisation or quality of life measures, however there is
uncertainty about these effects given the limited evidence available.12 studies
(4408 participants) investigating mineralocorticoid receptor antagonists (MRA)
were included with the quality of evidence assessed as moderate. MRA treatment
reduced heart failure hospitalisation (11% of participants in the intervention
arm versus 14% in the control arm; RR 0.82; 95% CI 0.69 to 0.98; NNTB 41; 3714
participants; 3 studies; moderate-quality evidence) however, little or no effect
on all-cause and cardiovascular mortality and quality of life measures was
observed. MRA treatment was associated with a greater risk of hyperkalaemia (16%
of participants in the intervention group versus 8% in the control group; RR
2.11; 95% CI 1.77 to 2.51; 4291 participants; 6 studies; high-quality
evidence).Eight studies (2061 participants) investigating angiotensin converting
enzyme inhibitors (ACEI) were included with the overall quality of evidence
assessed as moderate. The evidence suggested that ACEI treatment likely has
little or no effect on cardiovascular mortality, all-cause mortality, heart
failure hospitalisation, or quality of life. Data for the effect of ACEI on
hyperkalaemia were only available from one of the included studies.Eight studies
(8755 participants) investigating angiotensin receptor blockers (ARB) were
included with the overall quality of evidence assessed as high. The evidence
suggested that treatment with ARB has little or no effect on cardiovascular
mortality, all-cause mortality, heart failure hospitalisation, or quality of
life. ARB was associated with an increased risk of hyperkalaemia (0.9% of
participants in the intervention group versus 0.5% in the control group; RR 1.88;
95% CI 1.07 to 3.33; 7148 participants; 2 studies; high-quality evidence).We
identified a single ongoing placebo-controlled study investigating the effect of
angiotensin receptor neprilysin inhibitors (ARNI) in people with heart failure
with preserved ejection fraction. AUTHORS' CONCLUSIONS: There is evidence that
MRA treatment reduces heart failure hospitalisation in heart failure with
preserverd ejection fraction, however the effects on mortality related outcomes
and quality of life remain unclear. The available evidence for beta-blockers,
ACEI, ARB and ARNI is limited and it remains uncertain whether these treatments
have a role in the treatment of HFpEF in the absence of an alternative indication
for their use. This comprehensive review highlights a persistent gap in the
evidence that is currently being addressed through several large ongoing clinical
trials.
PMID- 29952096
TI - Delaying Anticancer Drug Delivery by Self-Assembly and Branching Effects of
Minimalist Dendron-Drug Conjugates.
AB - Self-assembly of a covalently-bound lipophilic drug to a dendronic scaffold for
making organic nanoparticles is reported as a proof of concept in
nanovectorization. A minimalist structural approach with a small PEG-dendron
conjugated to paclitaxel (PTX), incorporating safe succinic and gallic acids, is
efficient to provide the expected anticancer bioactivity, but also significantly
retards and targets intracellular delivery of PTX in 2D and 3D lung cancer cell
cultures. A branching effect of dendrons is crucial, when compared to linear PTX
conjugates. Transmission electron microscopy (TEM) and dynamic light-scattering
(DLS) studies indicate the formation of stable, low-disperse nanoparticles at 10
5 m in H2 0, which could also be responsible for the biological effects. An
ultrasensitive LC-MS/MS method was used for the determination of intracellular
PTX concentration over time, along with the survival rates of cancer cells.
Similarly, cell survival assays were successfully correlated to a 3D cell culture
with spheroids for mimicking tumors, when treated with PTX conjugates. Our work
opens the way to a full evaluation program required for new chemical entities.
PMID- 29952097
TI - Two and a half years on: data and experiences establishing a 'Virtual Clinic' for
joint replacement follow up.
AB - BACKGROUND: We use a 'Virtual Clinic' for follow up of hip and knee replacement
patients. The aim of this study was to investigate patient compliance, pain and
function, revision rates and surgeon experience using this system. METHODS: All
hip and knee replacements conducted from 2000 onwards were suitable for 'Virtual
Clinic' review. Between July 2014 and December 2016, all patients due for follow
up (at 1, 5 and 7 years post-operatively, or biennially thereafter) were mailed
an Oxford Hip or Knee Score and a request for a radiograph. A surgeon reviewed
the questionnaire and radiograph and decided whether face-to-face review was
necessary. We calculated compliance as the percentage of eligible patients who
completed the 'Virtual Clinic'. We used retrospective review of medical records
for all clinic participants to analyse Oxford scores, disposition following
appointment, and revision rates. We reviewed all clinic participants in December
2017 to identify any further revisions. Surgeon feedback was assessed by emailed
survey. RESULTS: A total of 2076 patients were due for follow up. 1405 patients
were contactable, and 710 completed the process. We calculated a 36% compliance
rate. Surgeons decided 162 (23%) patients with a mean Oxford score of 24.2
required face-to-face assessment. This identified 13 patients needing revision.
One other patient was revised for loosening which developed between 'Virtual
Clinic' appointments. Surgeon feedback indicated the inclusion of a 'comment'
section on the questionnaire as particularly useful. DISCUSSION: We describe our
adoption of a 'Virtual Clinic' for joint replacement follow up. We recommend this
system as a practical method of following up patients.
PMID- 29952098
TI - The need for a rationalist turn in evidence-based medicine.
AB - When evidence-based medicine (EBM) became established, its dominant rhetoric was
empiricist, in spite of rationalist elements in its practice. Exploring some of
the key statements about EBM down the years, the paper examines the tensions
between empiricism and rationalism and argues for a rationalist turn in EBM to
help to develop the next generation of scholarship in the field.
PMID- 29952099
TI - AHNS Series: Do you know your guidelines? Principles for treatment of cancer of
the paranasal sinuses: A review of the National Comprehensive Cancer Network
guidelines.
AB - This article is a continuation of the "Do You Know Your Guidelines" series. This
was launched as an initiative of the American Head and Neck Society to increase
the awareness of current best practices pertaining to head and neck cancer. The
National Comprehensive Cancer Network (NCCN) guidelines for managing cancer of
the paranasal sinuses are reviewed in a systematic fashion. These guidelines
outline the workup, treatment, and surveillance of patients with cancer of the
maxillary and ethmoid sinuses.
PMID- 29952100
TI - Is the Fourth Industrial Revolution relevant to you?
PMID- 29952101
TI - Nurses prescribing in Spain: The reality.
PMID- 29952103
TI - Identification of a missense mutation causing exon skipping in a
neurofibromatosis type 1 patient.
AB - Neurofibromatosis type 1 (NF1), caused by germ line mutations of the NF1 tumor
suppressor gene, is one of the most common autosomal dominant disorders. Here, we
reported a NF1 patient with the mutation NF1 c.4367+1G>C. This sequence change
locates at the first nucleotide of NF1 intron 32 within the consensus splice
site. Compared with NF1 c.4367G>C predicted to potentially damage the wild-type
donor site at c.4367, the NF1 c.4367+1G>C potentially abolishes this wild-type
donor site by in silico analysis. In vitro minigene assay revealed that the NF1
c.4367+1G>C may cause exon 32 skipping. Our result provides further evidence for
its clinical significance of NF1 c.4367+1G>C in clinical practise.
PMID- 29952104
TI - Outcomes of "diabetes-friendly" vs "diabetes-unfriendly" beta-blockers in older
nursing home residents with diabetes after acute myocardial infarction.
AB - AIMS: To assess whether nursing home (NH) residents with type 2 diabetes mellitus
(T2D) preferentially received "T2D-friendly" (vs "T2D-unfriendly") beta-blockers
after acute myocardial infarction (AMI), and to evaluate the comparative effects
of the two groups of beta-blockers. MATERIALS AND METHODS: This new-user
retrospective cohort study of NH residents with AMI from May 2007 to March 2010
used national data from the Minimum Data Set and Medicare system. T2D-friendly
beta-blockers were those hypothesized to increase peripheral glucose uptake
through vasodilation: carvedilol, nebivolol and labetalol. Primary outcomes were
hospitalizations for hypoglycaemia and hyperglycaemia in the 90 days after AMI.
Secondary outcomes were functional decline, death, all-cause re-hospitalization
and fracture hospitalization. We compared outcomes using binomial and multinomial
logistic regression models after propensity score matching. RESULTS: Of 2855 NH
residents with T2D, 29% initiated a T2D-friendly beta-blocker vs 24% of 6098
without T2D (P < 0.001). For primary outcomes among residents with T2D, T2D
friendly vs T2D-unfriendly beta-blockers were associated with a reduction in
hospitalized hyperglycaemia (odds ratio [OR] 0.45, 95% confidence interval [CI]
0.21-0.97), but unassociated with hypoglycaemia (OR 2.05, 95% CI 0.82-5.10). For
secondary outcomes, T2D-friendly beta-blockers were associated with a greater
rate of re-hospitalization (OR 1.26, 95% CI 1.01-1.57), but not death (OR 1.06,
95% CI 0.85-1.32), functional decline (OR 0.91, 95% CI 0.70-1.19), or fracture
(OR 1.69, 95% CI 0.40-7.08). CONCLUSIONS: In older NH residents with T2D, T2D
friendly beta-blocker use was associated with a lower rate of hospitalization for
hyperglycaemia, but a higher rate of all-cause re-hospitalization.
PMID- 29952105
TI - Advancement of Ag-Graphene Based Nanocomposites: An Overview of Synthesis and Its
Applications.
AB - Graphene has been employed as an excellent support for metal nanomaterials
because of its unique structural and physicochemical properties. Silver
nanoparticles (AgNPs) with exceptional properties have received considerable
attention in various fields; however, particle aggregation limits its
application. Therefore, the combination of AgNPs and graphene based
nanocomposites (Ag-graphene based nanocomposites) has been widely explored to
improve their properties and applications. Excitingly, enhanced antimicrobial,
catalytic, and surface enhanced Raman scattering properties are obtained after
their combination. In order to have a comprehensive knowledge of these
nanocomposites, this Review highlights the chemical and biological synthesis of
Ag-graphene nanocomposites. In particular, their applications as antimicrobial
agents, catalysts, and sensors in biomedicine, agricultural protection, and
environmental remediation and detection are covered. Meanwhile, the factors that
influence the synthesis and applications are also briefly discussed. Furthermore,
several important issues on the challenges and new directions are also provided
for further development of these nanocomposites.
PMID- 29952102
TI - Longitudinal white matter microstructural change in Parkinson's disease.
AB - Postmortem studies of Parkinson's disease (PD) suggest that Lewy body pathology
accumulates in a predictable topographical sequence, beginning in the olfactory
bulb, followed by caudal brainstem, substantia nigra, limbic cortex, and
neocortex. Diffusion-weighted imaging (DWI) is sensitive, if not specific, to
early disease-related white matter (WM) change in a variety of traumatic and
degenerative brain diseases. Although numerous cross-sectional studies have
reported DWI differences in cerebral WM in PD, only a few longitudinal studies
have investigated whether DWI change exceeds that of normal aging or coincides
with regional Lewy body accumulation. This study mapped regional differences in
the rate of DWI-based microstructural change between 29 PD patients and 43 age
matched controls over 18 months. Iterative within- and between-subject tensor
based registration was completed on motion- and eddy current-corrected DWI
images, then baseline versus follow-up difference maps of fractional anisotropy,
mean, radial, and axial diffusivity were analyzed in the Biological Parametric
Mapping toolbox for MATLAB. This analysis showed that PD patients had a greater
decline in WM integrity in the rostral brainstem, caudal subcortical WM, and
cerebellar peduncles, compared with controls. In addition, patients with
unilateral clinical signs at baseline experienced a greater rate of WM change
over the 18-month study than patients with bilateral signs. These findings
suggest that rate of WM microstructural change in PD exceeds that of normal aging
and is maximal during early stage disease. In addition, the neuroanatomic
locations (rostral brainstem and subcortical WM) of accelerated WM change fit
with current theories of topographic disease progression.
PMID- 29952106
TI - A pilot split-scalp study of combined fractional radiofrequency microneedling and
5% topical minoxidil in treating male pattern hair loss.
AB - BACKGROUND: Various trials have been conducted on the management of male pattern
hair loss (MPHL), but the outcomes often seem to be limited. Adjuvant therapies
are urgently needed. AIM: To evaluate the efficacy and safety of combined
fractional radiofrequency microneedling (FRM) and 5% topical minoxidil in the
treatment of male pattern hair loss. METHODS: In total, 19 Chinese men were
enrolled in this randomized, controlled, split-scalp trial. Participants received
monotherapy with 5% topical minoxidil twice daily to one half of the scalp, while
on the other half of the scalp the treatment with twice-daily 5% topical
minoxidil was combined with five sessions of FRM at 4-week intervals. Mean hair
count and hair thickness, global assessment by the investigators, subject self
assessment and adverse effects were assessed. RESULTS: After 5 months of
treatment, mean hair count increased from 44.12 +/- 21.58 to 73.14 +/- 25.45 on
the combined-therapy side and from 46.22 +/- 18.77 to 63.21 +/- 19.22 on the
monotherapy side, while mean hair thickness increased from 53 +/- 13 MUm to 71 +/
15 MUm and from 52 +/- 16 MUm to 66 +/- 14 MUm, respectively. Compared with the
monotherapy side, the combined-therapy side had a higher degree of improvement in
both hair count (P = 0.01) and hair thickness (P = 0.02). CONCLUSIONS: Combined
treatment with fractional radiofrequency microneedle and 5% topical minoxidil
could be an effective and safe treatment option for male pattern hair loss.
PMID- 29952107
TI - The Role of Liquid Ink Transport in the Direct Placement of Quantum Dot Emitters
onto Sub-Micrometer Antennas by Dip-Pen Nanolithography.
AB - Dip-pen nanolithography (DPN) is used to precisely position core/thick-shell
("giant") quantum dots (gQDs; >=10 nm in diameter) exclusively on top of silicon
nanodisk antennas (~500 nm diameter pillars with a height of ~200 nm), resulting
in periodic arrays of hybrid nanostructures and demonstrating a facile
integration strategy toward next-generation quantum light sources. A three-step
reading-inking-writing approach is employed, where atomic force microscopy (AFM)
images of the pre-patterned substrate topography are used as maps to direct
accurate placement of nanocrystals. The DPN "ink" comprises gQDs suspended in a
non-aqueous carrier solvent, o-dichlorobenzene. Systematic analyses of factors
influencing deposition rate for this non-conventional DPN ink are described for
flat substrates and used to establish the conditions required to achieve small
(sub-500 nm) feature sizes, namely: dwell time, ink-substrate contact angle and
ink volume. Finally, it is shown that the rate of solvent transport controls the
feature size in which gQDs are found on the substrate, but also that the number
and consistency of nanocrystals deposited depends on the stability of the gQD
suspension. Overall, the results lay the groundwork for expanded use of
nanocrystal liquid inks and DPN for fabrication of multi-component nanostructures
that are challenging to create using traditional lithographic techniques.
PMID- 29952108
TI - Ipsilateral versus contralateral placement of the pancreas allograft in pancreas
after kidney transplant recipients.
AB - BACKGROUND: In a diabetic, uremic kidney transplant recipient that may receive a
future pancreas after kidney (PAK) transplant, the kidney is typically implanted
on the left side in anticipation of the subsequent pancreas transplant on the
right side. In this study, we sought to determine if ipsilateral PAK (iPAK) is as
safe as contralateral PAK (cPAK). METHODS: The 115 PAK transplants (iPAK n = 57,
cPAK n = 58) were performed from 1997-2010 and results were compared between the
groups. RESULTS: Kidney graft survival and pancreas graft survival was similar
between the two groups. Kidney graft function according to serum creatinine and
eGFR was not different between the cPAK and the iPAK groups and there were no
episodes of kidney graft thrombosis in either group. Subgroup analyses focusing
on donor source also did not show worse outcomes for graft survivals in iPAK
group when compared to cPAK group. CONCLUSIONS: Pancreas and kidney graft
survival in PAK transplants is unaffected by the surgical procedure and iPAK is
safe.
PMID- 29952109
TI - Phosphodiesterase 4 inhibition reduces lung fibrosis following targeted type II
alveolar epithelial cell injury.
AB - Fibrosis of the lung constitutes a major clinical challenge and novel therapies
are required to alleviate the associated morbidity and mortality. Investigating
the antifibrotic efficacy of drugs that are already in clinical practice offers
an efficient strategy to identify new therapies. The phosphodiesterase 4 (PDE4)
inhibitors, approved for the treatment of chronic obstructive pulmonary disease,
harbor therapeutic potential for pulmonary fibrosis by augmenting the activity of
endogenous antifibrotic mediators that signal through cyclic AMP. In this study,
we tested the efficacy of several PDE4 inhibitors including a novel compound
(Compound 1) in a murine model of lung fibrosis that results from a targeted type
II alveolar epithelial cell injury. We also compared the antifibrotic activity of
PDE4 inhibition to the two therapies that are FDA-approved for idiopathic
pulmonary fibrosis (pirfenidone and nintedanib). We found that both preventative
(day 0-21) and therapeutic (day 11-21) dosing regimens of the PDE4 inhibitors
significantly ameliorated the weight loss and lung collagen accumulation that are
the sequelae of targeted epithelial cell damage. In a therapeutic protocol, the
reduction in lung fibrosis with PDE4 inhibitor administration was equivalent to
pirfenidone and nintedanib. Treatment with this class of drugs also resulted in a
decrease in plasma surfactant protein D concentration, a reduction in the plasma
levels of several chemokines implicated in lung fibrosis, and an in vitro
inhibition of fibroblast profibrotic gene expression. These results motivate
further investigation of PDE4 inhibition as a treatment for patients with
fibrotic lung disease.
PMID- 29952110
TI - RGB-Color Intensiometric Indicators to Visualize Spatiotemporal Dynamics of ATP
in Single Cells.
AB - Adenosine triphosphate (ATP) provides energy for the regulation of multiple
cellular processes in living organisms. Capturing the spatiotemporal dynamics of
ATP in single cells is fundamental to our understanding of the mechanisms
underlying cellular energy metabolism. However, it has remained challenging to
visualize the dynamics of ATP in and between distinct intracellular organelles
and its interplay with other signaling molecules. Using single fluorescent
proteins, multicolor ATP indicators were developed, enabling the simultaneous
visualization of subcellular ATP dynamics in the cytoplasm and mitochondria of
cells derived from mammals, plants, and worms. Furthermore, in combination with
additional fluorescent indicators, the dynamic interplay of ATP, cAMP, and Ca2+
could be visualized in activated brown adipocyte. This set of indicator tools
will facilitate future research into energy metabolism.
PMID- 29952111
TI - Re: The incidence, characteristics, managements and outcomes of anaphylaxis in
pregnancy: a population-based descriptive study: Latex anaphylaxis in pregnancy:
gone or forgotten?
PMID- 29952112
TI - Printed Electronics Based on Inorganic Semiconductors: From Processes and
Materials to Devices.
AB - Following the ever-expanding technological demands, printed electronics has shown
palpable potential to create new and commercially viable technologies that will
benefit from its unique characteristics, such as, large-area and wide range of
substrate compatibility, conformability and low-cost. Through the last few
decades, printed/solution-processed field-effect transistors (FETs) and circuits
have witnessed immense research efforts, technological growth and increased
commercial interests. Although printing of functional inks comprising organic
semiconductors has already been initiated in early 1990s, gradually the
attention, at least partially, has been shifted to various forms of inorganic
semiconductors, starting from metal chalcogenides, oxides, carbon nanotubes and
very recently to graphene and other 2D semiconductors. In this review, the entire
domain of printable inorganic semiconductors is considered. In fact, thanks to
the continuous development of materials/functional inks and novel design/printing
strategies, the inorganic printed semiconductor-based circuits today have reached
an operation frequency up to several hundreds of kilohertz with only a few
nanosecond time delays at the individual FET/inverter levels; in this regard,
often circuits based on hybrid material systems have been found to be
advantageous. At the end, a comparison of relative successes of various printable
inorganic semiconductor materials, the remaining challenges and the available
future opportunities are summarized.
PMID- 29952113
TI - Cordyceps cicadae mycelia and its active compound HEA exert beneficial effects on
blood glucose in type 2 diabetic db/db mice.
AB - BACKGROUND: This is the first study to investigate the therapeutic effects of
Cordyceps cicadae (C. cicadae) mycelia and its active compound N6 -(2
hydroxyethyl)adenosine (HEA) on blood glucose in genetically diabetic mice.
RESULTS: Forty mice, 9 weeks of age, were divided into normal control, diabetic
control, and three C. cicadae mycelia treated diabetic groups. After 9 weeks of
continuous supplementation, the oral glucose tolerance test (OGTT) and
homeostasis model of assessment-insulin resistance index showed significant
glucose tolerance with C. cicadae mycelia. Furthermore, the effect of HEA is
similar to that of C. cicadae mycelia in an OGTT, suggesting that HEA could be
the major factor responsible for the functional properties of C. cicadae mycelia.
CONCLUSION: Based on these findings, it is suggested that the therapeutic effect
of C. cicadae mycelia may be driven by one of its active components, HEA, which
could alleviate many diabetes complications in genetically obese mice and may
offer promise as a supplement for diabetes management. (c) 2018 Society of
Chemical Industry.
PMID- 29952115
TI - How Do You Solve a Problem Like Juul?
PMID- 29952114
TI - Spatial heterogeneity in species composition constrains plant community responses
to herbivory and fertilisation.
AB - Environmental change can result in substantial shifts in community composition.
The associated immigration and extinction events are likely constrained by the
spatial distribution of species. Still, studies on environmental change typically
quantify biotic responses at single spatial (time series within a single plot) or
temporal (spatial beta diversity at single time points) scales, ignoring their
potential interdependence. Here, we use data from a global network of grassland
experiments to determine how turnover responses to two major forms of
environmental change - fertilisation and herbivore loss - are affected by species
pool size and spatial compositional heterogeneity. Fertilisation led to higher
rates of local extinction, whereas turnover in herbivore exclusion plots was
driven by species replacement. Overall, sites with more spatially heterogeneous
composition showed significantly higher rates of annual turnover, independent of
species pool size and treatment. Taking into account spatial biodiversity aspects
will therefore improve our understanding of consequences of global and
anthropogenic change on community dynamics.
PMID- 29952117
TI - Importance of contextual variables related to cavitated lesions in 5-year-old
children.
AB - BACKGROUND: Dental caries have a high prevalence in children and need to evaluate
their individual and contextual determinants. AIM: To evaluate the importance of
individual and contextual determinants on the occurrence of cavitated lesions in
5-year-old children. DESIGN: A cross-sectional study was conducted with 769
preschoolers in a city in northeastern Brazil. Parents/caregivers answered
questionnaires addressing psychological aspects, socio-demographic
characteristics and the child's oral health. The diagnosis of dental caries
(cavitated lesion) was performed using the ICDAS-II. Variables related to the
context were collected at the preschools and official municipal publications.
Unadjusted and adjusted multilevel Poisson regression models with robust variance
correction were used. RESULTS: The prevalence of cavitated lesions was 58.8%. In
the analysis adjusted by individual determinants, low household income (PR =
1.61; 95%CI:1.27-2.05), lower parent's/caregiver's schooling (PR = 1.57;
95%CI:1.20-2.05), not visited to the dentist (PR = 0.77; 95%CI:0.62-0.94),
brushing frequency under 2 times per day (PR = 2.17; 95%CI:1.35-3.51) and weak
parent's/caregiver's SOC (PR = 1.30; 95%CI:1.09-1.56) were associated with
cavitated lesions. However, after the incorporation of the contextual
determinants, parent's/caregiver's schooling and SOC lost their association.
Considering contextual factors, children attending public preschools (PR = 1.66;
95%CI:1.34-2.05) and/or smaller preschools (PR = 1.001; 95%CI:1.001-1.002) had a
greater probability of exhibiting cavitated lesions. CONCLUSION: Contextual
variables were more important to the occurrence cavitated lesions than individual
socioeconomic variables.
PMID- 29952116
TI - The pivotal role of DNA methylation in the radio-sensitivity of tumor
radiotherapy.
AB - Radiotherapy is an important modality for treatment of carcinomas; however, radio
resistance is still a difficult problem. Aberrant epigenetic alterations play an
important role in cancer development. Among epigenetic parameters, DNA
methylation has arguably attracted the most attention in the radio-resistance
process. To determine the role of DNA methylation in radiation resistance,
several studies were conducted. We summarized previous studies on the role of DNA
methylation in radiotherapy. We observed this significant role of DNA methylation
in genes related to DNA repair, cell proliferation, cell cycle process, and re
oxygenation. Furtherly, we also conclude the predictive effect of DNA methylation
on tumor radio-sensitivity and the using of DNA methyltransferase inhibitors in
clinical practice. DNA methylation plays a pivotal role in the radio-sensitivity
of tumor radio-therapy. While hyper-methylation or hypo-methylation of genes is
related to gene functions.
PMID- 29952118
TI - Synthesis and biological activity of analogs of the antifungal antibiotic UK-2A.
I. Impact of picolinamide ring replacement.
AB - BACKGROUND: The antifungal antibiotic UK-2A strongly inhibits mitochondrial
electron transport at the Qi site of the cytochrome bc1 complex. Previous reports
have described semi-synthetic modifications of UK-2A to explore the structure
activity relationship (SAR), but efforts to replace the picolinic acid moiety
have been limited. RESULTS: Nineteen UK-2A analogs were prepared and evaluated
for Qi site (cytochrome c reductase) inhibition and antifungal activity. While
the majority are weaker Qi site inhibitors than UK-2A (IC50 , 3.8 nM), compounds
2, 5, 13 and 16 are slightly more active (IC50 , 3.3, 2.02, 2.89 and 1.55 nM,
respectively). Compared to UK-2A, compounds 13 and 16 also inhibit growth of
Zymoseptoria tritici and Leptosphaeria nodorum more strongly, while 2 and 13
provide stronger control of Z. tritici and Puccinia triticina in glasshouse
tests. The relative activities of compounds 1-19 are rationalized based on a
homology model constructed for the Z. tritici Qi binding site. Physical
properties of compounds 1-19 influence translation of intrinsic activity to
antifungal growth inhibition and in planta disease control. CONCLUSIONS: The 3
hydroxy-4-methoxy picolinic acid moiety of UK-2A can be replaced by a variety of
o-hydroxy-substituted arylcarboxylic acids that retain strong activity against Z.
tritici and other agriculturally relevant fungi. (c) 2018 Society of Chemical
Industry.
PMID- 29952120
TI - Comparative RNA-seq analysis of nickel hyperaccumulating and non-accumulating
populations of Senecio coronatus (Asteraceae).
AB - Most metal hyperaccumulating plants accumulate nickel, yet the molecular basis of
Ni hyperaccumulation is not well understood. We chose Senecio coronatus to
investigate this phenomenon as this species displays marked variation in shoot Ni
content across ultramafic outcrops in the Barberton Greenstone Belt (South
Africa), thus allowing an intraspecific comparative approach to be employed. No
correlation between soil and shoot Ni contents was observed, suggesting that this
variation has a genetic rather than environmental basis. This was confirmed by
our observation that the accumulation phenotype of plants from two
hyperaccumulator and two non-accumulator populations was maintained when the
plants were grown on a soil mix from these four sites for 12 months. We analysed
the genetic variation among 12 serpentine populations of S. coronatus, and used
RNA-seq for de novo transcriptome assembly and analysis of gene expression in
hyperaccumulator versus non-accumulator populations. Genetic analysis revealed
the presence of hyperaccumulators in two well supported evolutionary lineages,
indicating that Ni hyperaccumulation may have evolved more than once in this
species. RNA-Seq analysis indicated that putative homologues of transporters
associated with root iron uptake in plants are expressed at elevated levels in
roots and shoots of hyperaccumulating populations of S. coronatus from both
evolutionary lineages. We hypothesise that Ni hyperaccumulation in S. coronatus
may have evolved through recruitment of these transporters, which play a role in
the iron-deficiency response in other plant species.
PMID- 29952119
TI - The relationship between naevus count, memory function and telomere length in the
Twins UK cohort.
AB - The presence of a skin-brain connection whereby alterations in the skin can
inform on mechanisms underlying neurodegenerative diseases is increasingly
recognized. In this study, we used a discovery (n = 321) and replication (n =
147) sample from the Twins UK population to test the association between naevus
count and memory function, and its mediation by telomeres. Memory function was
assessed in 1999 and 2009 using the paired associates learning test (PAL), while
naevus count and leucocyte telomere length (LTL, assessed by the terminal
restriction fragment assay) were measured once. Higher baseline naevus count was
significantly associated with fewer errors at the baseline and follow-up PAL, as
well as with change in PAL score over 10 years. This association was
significantly attenuated after adjustment for LTL. The significant association
between naevus count and PAL score was reproduced in the replication sample.
These findings suggest that melanocytes might be used as model system to study
the biological ageing pathways involved in neurodegeneration.
PMID- 29952121
TI - The Utility of Nanopore Technology for Protein and Peptide Sensing.
AB - Resistive pulse nanopore sensing enables label-free single-molecule analysis of a
wide range of analytes. An increasing number of studies have demonstrated the
feasibility and usefulness of nanopore sensing for protein and peptide
characterization. Nanopores offer the potential to study a variety of protein
related phenomena that includes unfolding kinetics, differences in unfolding
pathways, protein structure stability, and free-energy profiles of DNA-protein
and RNA-protein binding. In addition to providing a tool for fundamental protein
characterization, nanopores have also been used as highly selective protein
detectors in various solution mixtures and conditions. This review highlights
these and other developments in the area of nanopore-based protein and peptide
detection.
PMID- 29952122
TI - Evaluating the effectiveness of a preclinical practice of tooth preparation using
digital training system: A randomised controlled trial.
AB - PURPOSE: This study aimed to evaluate the effectiveness of preclinical training
on ceramic crown preparation using digital training system compared with
traditional training method. MATERIALS AND METHODS: A sample of 66 participating
fourth-year undergraduate dental students were randomly assigned to one of two
groups for ceramic crown preparation: experimental group as trained using digital
method with Online Peer-Review System (OPRS) and Real-time Dental Training and
Evaluation System (RDTES); control group as trained using traditional method with
instructor demonstration and evaluation. At the completion of training periods,
both groups performed the preparation of ceramic crown of upper left central
incisor, which were blindly scored by the experienced instructors under the pre
defined assessment criteria. The results of both were compared using Student's t
test or Wilcoxon signed rank test. The level of significance was P < .05. The
questionnaires regarding the benefits or drawbacks of digital training system
were answered by the students of experimental group. RESULTS: Five of 15 items in
the assessment outcome of the digital group were significantly better than the
traditional group. The questionnaire results from the students of the
experimental group indicated 96.97% of the students agreed or strongly agreed
that using digital training system could better improve the practical ability
than traditional method. The total scores of practical results were significantly
positively correlated with the points of the questionnaires. CONCLUSION: The
digital training system with OPRS and RDTES might be a good alternative to the
traditional training method in the preclinical course of dental practice.
PMID- 29952123
TI - Exoproteome Analysis of Human Pathogenic Dermatophyte Species and Identification
of Immunoreactive Proteins.
AB - PURPOSE: Increasing incidence of onychomycosis and tinea pedis in humans of
industrialized countries together with deep tissue infections are a therapeutic
challenge in clinical mycology. For a better understanding of the pathology and
immunology of infection, the authors analyze the exoproteomes of three reference
strains of the most common clinical dermatophyte species (Trichophyton rubrum,
Trichophyton interdigitale, Arthroderma benhamiae) and of Trichophyton strains
isolated from affected patients. EXPERIMENTAL DESIGN: Extracellular proteins of
those in vitro grown strains are separated via 2D High Performance
Electrophoresis and identified by mass spectrometry to find proteins with
provoked host immune reactivity. RESULTS: More than 80 secreted proteins
including virulence factors such as peptidases and other hydrolases are
identified. By Western blotting with respective patient sera, up to 31 proteins
with significant antigen-antibody reactions are detected in comparison with
control sera, for example, peptidases as well as several oxidoreductases. One
protein, beta-glucosidase F2SZI9 seems to be a commonly processed antigen in all
Trichophyton infections. CONCLUSIONS AND CLINICAL RELEVANCE: These first global
exoproteome data of three dermatophyte species can be a stepping stone on the way
to further study the molecular mechanisms of Trichophyton pathogenicity
associated traits. Possible candidates for potential new diagnostic methods or
vaccination have to be validated in further investigations.
PMID- 29952125
TI - Evaluating the quality of medical evidence in real-world contexts.
AB - How should the quality of medical evidence be evaluated? Proponents of evidence
based medicine advocate the use evidence hierarchies to rank the quality of
evidence on the basis that certain methods produce more reliable evidence. Some
criticisms of this approach focus on whether certain methods deserve their place
in the hierarchy, while others claim that evidence hierarchies should be
abandoned in favour of other evidence assessment techniques. We claim that this
debate pays insufficient attention to the real-world contexts in which medical
decisions are made. To address this limitation, we explore the value of using
evidence hierarchies and other evidence assessment techniques in differing
contexts of medical decision making and argue that the way in which the quality
of medical evidence should be evaluated depends on context. Focusing the
discussion of the evaluation of medical evidence on real-world contexts has
implications for the viability of the principle of total evidence.
PMID- 29952124
TI - Periodic limb movements during sleep are associated with cardiovascular diseases:
A systematic review and meta-analysis.
AB - Periodic limb movements during sleep present with repetitive movements, typically
in the lower limbs, during sleep. Periodic limb movements during sleep have been
proposed to be associated with increased risk of heart diseases. The aim of this
study was to examine the co-morbidity rates of heart disease, including acute
myocardial infarction, coronary artery disease and cardiovascular disease, in
subjects with or without periodic limb movements during sleep through a meta
analysis. An electronic review of PubMed, Embase, ScienceDirect, Cochrane
Library, ProQuest, Web of Science, ClinicalKey and ClinicalTrials.gov was
performed. Clinical studies, case-controlled trials and cohort studies were all
included in the search. Case reports or series, and non-clinical studies were
excluded. A meta-analysis of the results of six studies comparing the prevalence
of coronary artery disease/acute myocardial infarction/cardiovascular disease in
subjects with/without periodic limb movements during sleep was performed. There
were significantly higher co-morbidity rates of coronary artery disease (odds
ratio = 1.568, 95% confidence interval: 1.187-2.073, p = 0.002) and
cardiovascular disease (odds ratio = 1.279, 95% confidence interval: 1.095-1.494,
p = 0.002), but not acute myocardial infarction (odds ratio = 1.272, 95%
confidence interval = 0.942-1.718, p = 0.117), in the periodic limb movements
during sleep group than in the non-periodic limb movements during sleep group.
This meta-analysis highlights the importance of a significantly high prevalence
of coronary artery disease and cardiovascular disease in subjects with periodic
limb movements during sleep. Further studies should be focused on the potential
pathophysiology, and whether treatment for periodic limb movements during sleep
can improve the outcome of heart disease.
PMID- 29952126
TI - Effects of experimental light at night on extra-pair paternity in a songbird.
AB - Light pollution is increasing worldwide and significantly affects animal
behavior. In birds, these effects include advancement of morning activity and
onset of dawn song, which may affect extra-pair paternity. Advanced dawn song of
males may stimulate females to engage in extra-pair copulations, and the earlier
activity onset may affect the males' mate guarding behavior. Earlier work showed
an effect of light at night on extra-pair behavior, but this was in an area with
other anthropogenic disturbances. Here, we present a two-year experimental study
on effects of light at night on extra-pair paternity of great tits (Parus major).
Previously dark natural areas were illuminated with white, red, and green LED
lamps and compared to a dark control. In 2014, the proportion of extra-pair young
in broods increased with distance to the red and white lamps (i.e., at lower
light intensities), but decreased with distance to the poles in the dark control.
In 2013, we found no effects on the proportion of extra-pair young. The total
number of offspring sired by a male was unaffected by artificial light at night
in both years, suggesting that potential changes in female fidelity in pairs
breeding close to white and red light did not translate into fitness benefits for
the males of these pairs. Artificial light at night might disrupt the natural
patterns of extra-pair paternity, possibly negates potential benefits of extra
pair copulations and thus could alter sexual selection processes in wild birds.
PMID- 29952127
TI - Potential oscillators and keystone modules in food webs.
AB - Food web theory suggests that the placement of a weak interaction is critical
such that under some conditions even one well-placed weak interaction can
stabilise multiple strong interactions. This theory suggests that complex stable
webs may be built from pivotal weak interactions such that the removal of even
one to a few keystone interactions can have significant cascading impacts on
whole system diversity and structure. However, the connection between weak
interactions, derived from the theory of modular food web components, and
keystone species, derived from empirical results, is not yet well understood.
Here, we develop numerical techniques to detect potential oscillators hidden in
complex food webs, and show that, both in random and real food webs, keystone
consumer-resource interactions often operate to stabilise them. Alarmingly, this
result suggests that nature frequently may be dangerously close to precipitous
change with even the loss of one or a few weakly interacting species.
PMID- 29952128
TI - The trafficking of metal ion transporters of the Zrt- and Irt-like protein
family.
AB - Metal ion transporters of the Zrt- and Irt-like protein (ZIP, or SLC39A) family
transport zinc, iron, manganese and/or cadmium across cellular membranes and into
the cytosol. The 14 human ZIP family proteins are expressed in a wide variety of
tissues and function in many different cellular processes. Many of these proteins
(including ZIP1, 2, 3, 4, 5, 6/10, 8, 9, 11, 12, 14) are situated, at least some
of the time, on the plasma membrane, where they mediate metal ion uptake into
cells. Their level on the cell surface can be controlled rapidly via protein
trafficking in response to the ions they transport. For example, the cell surface
level of many ZIPs (including ZIP1, 3, 4, 8 and 12) is mediated by the available
concentration of zinc. Zinc depletion causes a decrease in endocytosis and
degradation, resulting in more ZIP on the surface to take up the essential ion.
ZIP levels on the cell surface are a balance between endocytosis, recycling and
degradation. We review the trafficking mechanisms of human ZIP proteins,
highlighting possible targeting motifs and suggesting a model of zinc-mediated
endocytic trafficking. We also provide two possible models for ZIP14 trafficking
and degradation.
PMID- 29952129
TI - Case of the missing metastatic melanoma?
PMID- 29952130
TI - Temporal Analyses of Barley Malting Stages Using Shotgun Proteomics.
AB - Malt derived from barley malting is an essential raw material for beer brewing.
In this study, we performed the first dynamic proteome survey during barley
malting using a gel-free proteomics approach. This entailed in-solution tryptic
digestion of precipitated proteins and analysis of peptides by nanoliquid
chromatography coupled with tandem mass spectrometry. A total of 1418 proteins
were identified from the five malting stages: Steep, 1, 3, 5 days after
germination, and end of Kiln. About 900 proteins identified in this analysis were
uncharacterized or predicted proteins. Integrating information from Uniprot90,
Uniprot50, Pfam, Interpro databases and gene ontologies from EnsemblPlants, 796
of the predicted and uncharacterized proteins were provided functional
annotations. Nearly 63% of the identified proteins were present during all the
five time points suggesting a coordinated activation of major metabolic pathways
during malting. GO enrichment analysis showed over-representation of proteins
associated with translation, carbohydrate metabolism, and stress response.
Analysis of variance of the spectral counts of proteins present in all the five
malting stages identified 205 proteins with significant differences in their
abundance. Proteins associated with carbohydrate metabolism especially enzyme
activity regulation provide novel targets for malting barley breeding and for
predicting malting quality.
PMID- 29952131
TI - Tobacco and cannabis use in college students are predicted by sex-dimorphic
interactions between MAOA genotype and child abuse.
AB - BACKGROUND: Postsecondary students in Western countries exhibit a high prevalence
of cannabis and tobacco use disorders. The etiology of these problems is
contributed by several psychosocial factors, including childhood adversity and
trauma; however, the mechanisms whereby these environmental determinants
predispose to the use of these substances remain elusive, due to our poor
knowledge of genetic and biological moderators. Converging evidence points to the
monoamine oxidase A (MAOA) gene as a moderator of the effects of lifetime stress
on the initiation of substance use. AIMS: Building on these premises, in this
study, we analyzed whether MAOA upstream variable number tandem repeat (uVNTR)
alleles interact with child maltreatment history to predict for lifetime cannabis
and tobacco consumption. MATERIALS AND METHODS: Five hundred college students
(age: 18-25 years) from a large Midwestern University were surveyed for their
child maltreatment history (encompassing emotional, physical, and sexual abuse,
as well as emotional and physical neglect) and lifetime consumption of cannabis
and tobacco. Saliva samples were obtained to determine the MAOA uVNTR genotype of
each participant. RESULTS: In female students, lifetime tobacco and cannabis use
was predicted by the interaction of physical and emotional abuse with high
activity MAOA allelic variants; conversely, in males, the interaction of low
activity MAOA alleles and physical abuse was associated with lifetime use of
tobacco, but not cannabis. DISCUSSION: These findings collectively suggest that
the vulnerability to smoke tobacco and cannabis is predicted by sex-dimorphic
interactions of MAOA gene with childhood abuse. CONCLUSION: These biosocial
underpinnings of tobacco and cannabis use may prove important in the development
of novel personalized preventive strategies for substance use disorders in
adolescents.
PMID- 29952132
TI - alpha-particle therapy for synovial sarcoma in the mouse using an astatine-211
labeled antibody against frizzled homolog 10.
AB - Synovial sarcoma (SS) is a rare yet refractory soft-tissue sarcoma that
predominantly affects young adults. We show in a mouse model that
radioimmunotherapy (RIT) with an alpha-particle emitting anti-Frizzled homolog 10
(FZD10) antibody, synthesized using the alpha-emitter radionuclide astatine-211
(211 At-OTSA101), suppresses the growth of SS xenografts more efficiently than
the corresponding beta-particle emitting anti-FZD10 antibody conjugated with the
beta-emitter yettrium-90 (90 Y-OTSA101). In biodistribution analysis, 211 At was
increased in the SS xenografts but decreased in other tissues up to 1 day after
injection as time proceeded, albeit with a relatively higher uptake in the
stomach. Single 211 At-OTSA101 doses of 25 and 50 MUCi significantly suppressed
SS tumor growth in vivo, whereas a 50-MUCi dose of 90 Y-OTSA101 was needed to
achieve this. Importantly, 50 MUCi of 211 At-OTSA101 suppressed tumor growth
immediately after injection, whereas this effect required several days in the
case of 90 Y-OTSA101. Both radiolabeled antibodies at the 50-MUCi dosage level
significantly prolonged survival. Histopathologically, severe cellular damage
accompanied by massive cell death was evident in the SS xenografts at even 1 day
after the 211 At-OTSA101 injection, but these effects were relatively milder with
90 Y-OTSA101 at the same timepoint, even though the absorbed doses were
comparable (3.3 and 3.0 Gy, respectively). We conclude that alpha-particle RIT
with 211 At-OTSA101 is a potential new therapeutic option for SS.
PMID- 29952134
TI - Proteomic Profiling of Enteroid Cultures Skewed toward Development of Specific
Epithelial Lineages.
AB - Recently, 3D small intestinal organoids (enteroids) have been developed from
cultures of intestinal stem cells which differentiate in vitro to generate all
the differentiated epithelial cell types associated with the intestine and mimic
the structural properties of the intestine observed in vivo. Small-molecule drug
treatment can skew organoid epithelial cell differentiation toward particular
lineages, and these skewed enteroids may provide useful tools to study specific
epithelial cell populations, such as goblet and Paneth cells. However, the extent
to which differentiated epithelial cell populations in these skewed enteroids
represent their in vivo counterparts is not fully understood. This study utilises
label-free quantitative proteomics to determine whether skewing murine enteroid
cultures toward the goblet or Paneth cell lineages results in changes in
abundance of proteins associated with these cell lineages in vivo. Here,
proteomics data confirms that skewed enteroids recapitulate important features of
the in vivo gut environment, demonstrating that they can serve as useful models
for the investigation of normal and disease processes in the intestine.
Furthermore, comparison of mass spectrometry data with histology data contained
within the Human Protein Atlas identifies putative novel markers for goblet and
Paneth cells.
PMID- 29952133
TI - Proteomics in Veterinary Medicine and Animal Science: Neglected Scientific
Opportunities with Immediate Impact.
AB - Animal/veterinary proteomics is an evolving field which holds a great promise not
only for fundamental and applied discoveries regarding biology and pathology of
domestic species, but can also be implemented in comparative applications of
human diseases research. Experimental proteomics in domestic animals have
advantages over use of rodents, such as multiple sampling in time series and
availability of biological samples in sufficient volume for multiple analyses,
such that both experimental and natural disease processes can be investigated.
While there are certain technical limitations in the expansion of the field, they
can currently be circumvented and in the future mastered with a greater
participation of proteomic experts, which will in turn drive the accessibility of
species-specific reagents, data volume expansion in bioinformatic databases, and
increased funding. This Viewpoint highlights some comparative proteomics studies
addressing important issues and encourages readers to expand their horizons of
domestic animal proteomics research. It will hopefully inspire new fruitful
collaborations between veterinary and animal scientists and proteomic specialists
for research in these areas that can have immediate and direct impact on health,
society, and the economy.
PMID- 29952135
TI - 3D Printing Nanoscale Bioactive Glass Scaffolds Enhance Osteoblast Migration and
Extramembranous Osteogenesis through Stimulating Immunomodulation.
AB - Bioactive glass (BG) can repair bone defects, however, it is not clear whether BG
has the ability for bone augmentation without making any bone defect. Unlike the
intramembranous osteogenesis in bone defect repair, the extramembranous
osteogenesis occurs outside the cortical bone and the osteoprogenitor cells show
the reversed migration. Herein, nanoscale bioactive glass scaffolds (BGSs) are
fabricated, and their role and immunomodulation-related mechanism in the
extramembranous osteogenesis are investigated. The in vitro migration and
differentiation of calvaria preosteoblasts are studied by culturing with
peripheral macrophage-conditioned medium after stimulating with BGSs. The results
indicate that the proinflammatory environment significantly promotes
preosteoblast migration, but has limited effect on osteogenic differentiation.
However, the anti-inflammatory environment and BGSs significantly increase the
osteogenic differentiation of preosteoblasts. The in vivo extramembranous
osteogenesis evaluation shows that the active osteogenesis is observed near the
skull. The osteoblasts derived from the reverse migration of cranial cells can be
confirmed by comparing with the scaffolds implanted in back subcutaneous which is
just colonized by fibrous tissue. This study may bring a fresh perspective for BG
in bone regeneration and explore the osteogenic immunomodulation of peripheral
macrophages in a nonosteogenic environment.
PMID- 29952136
TI - Dry Chemistry of Ferrate(VI): A Solvent-Free Mechanochemical Way for Versatile
Green Oxidation.
AB - The +6 oxidation state of iron generally exists in the form of ferrate(VI) with
high redox potential and environmentally friendly nature. Although ferrate(VI)
has been known for over a century, its chemistry is still limited to the solvent
based reactions that suffers from the insolubility/instability of this oxidant
and the environmental issues caused by hazardous solvents. Herein, we explore the
solvent-free reactivity of ferrate(VI) under mechanical milling, revealing that
its strong oxidizing power is accessible in the "dry" solid state towards a broad
variety of substrates, for example, aromatic alcohols/aldehydes and carbon
nanotubes. More significantly, solvent-free mechanochemistry also reshapes the
oxidizing ability of ferrate(VI) due to the underlying solvent-free effect and
the promotive mechanical actions. This study opens up a new chemistry of
ferrate(VI) with promising application in green oxidative transformation of both
organic and inorganic substrates.
PMID- 29952138
TI - Combining X-Ray Whole Powder Pattern Modeling, Rietveld and Pair Distribution
Function Analyses as a Novel Bulk Approach to Study Interfaces in
Heteronanostructures: Oxidation Front in FeO/Fe3 O4 Core/Shell Nanoparticles as a
Case Study.
AB - Understanding the microstructure in heterostructured nanoparticles is crucial to
harnessing their properties. Although microscopy is ideal for this purpose, it
allows for the analysis of only a few nanoparticles. Thus, there is a need for
structural methods that take the whole sample into account. Here, a novel bulk
approach based on the combined analysis of synchrotron X-ray powder diffraction
with whole powder pattern modeling, Rietveld and pair distribution function is
presented. The microstructural temporal evolution of FeO/Fe3 O4 core/shell
nanocubes is studied at different time intervals. The results indicate that a two
phase approach (FeO and Fe3 O4 ) is not sufficient to successfully fit the data
and two additional interface phases (FeO and Fe3 O4 ) are needed to obtain
satisfactory fits, i.e., an onion-type structure. The analysis shows that the Fe3
O4 phases grow to some extent (~1 nm) at the expense of the FeO core. Moreover,
the FeO core progressively changes its stoichiometry to accommodate more oxygen.
The temporal evolution of the parameters indicates that the structure of the
FeO/Fe3 O4 nanocubes is rather stable, although the exact interface structure
slightly evolves with time. This approach paves the way for average studies of
interfaces in different kinds of heterostructured nanoparticles, particularly in
cases where spectroscopic methods have some limitations.
PMID- 29952137
TI - Inspiratory and expiratory resistance cause right-to-left bubble passage through
the foramen ovale.
AB - A patent foramen ovale (PFO) is linked to increased risk of decompression illness
in divers. One theory is that venous gas emboli crossing the PFO can be minimized
by avoiding lifting, straining and Valsalva maneuvers. Alternatively, we
hypothesized that mild increases in external inspiratory and expiratory
resistance, similar to that provided by a SCUBA regulator, recruit the PFO. Nine
healthy adults with a Valsalva-proven PFO completed three randomized trials
(inspiratory, expiratory, and combined external loading) with six levels of
increasing external resistance (2-20 cmH2 O/L/sec). An agitated saline contrast
echocardiogram was performed at each level to determine foramen ovale patency.
Contrary to our hypothesis, there was no relationship between the number of
subjects recruiting their PFO and the level of external resistance. In fact, at
least 50% of participants recruited their PFO during 14 of 18 trials and there
was no difference between the combined inspiratory, expiratory, or combined
external resistance trials (P > 0.05). We further examined the relationship
between PFO recruitment and intrathoracic pressure, estimated from esophageal
pressure. Esophageal pressure was not different between participants with and
without a recruited PFO. Intrasubject variability was the most important
predictor of PFO patency, suggesting that some individuals are more likely to
recruit their PFO in the face of even mild external resistance. Right-to-left
bubble passage through the PFO occurs in conditions that are physiologically
relevant to divers. Transthoracic echocardiography with mild external breathing
resistance may be a tool to identify divers that are at risk of PFO-related
decompression illness.
PMID- 29952139
TI - Altered near-infrared spectroscopy response to breath-holding in patients with
fibromyalgia.
AB - Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread pain
and a heightened response to pressure. Most medical researches pointed out that
FM patients with endothelial dysfunction and arterial stiffness. A continuous
wave near-infrared spectroscopy (NIRS) system is used in present study to measure
the hemodynamic changes elicited by breath-holding task in patients with FM. Each
patient completed a questionnaire survey including demographics, characteristics
of body pain, associated symptoms, headache profiles and Hospital Anxiety and
Depression Scale. A total of 27 FM patients and 26 health controls were enrolled.
In comparison with healthy controls, patients with FM showed lower maximal and
averaged change of oxyhemoglobin concentration in both the left (1.634 +/-0.890
and 0.810 +/-0.525 MUM) and the right (1.576 +/-0.897 and 0.811 +/-0.601 MUM)
prefrontal cortex than healthy controls (P < .05 for both sides) during the
breath-holding task. In conclusion, FM is associated with altered cerebrovascular
reactivity measured by NIRS and breath-holding task, which may reflect
endothelial dysfunction or arterial stiffness. Oxygenated hemoglobin
concentration changes of healthy controls and FM patients.
PMID- 29952140
TI - Legislation governing genetically modified and genome-edited crops in Europe: the
need for change.
AB - The European Commission's assessment and approval process for genetically
modified (GM) crops has resulted in only two GM crop varieties being licensed for
cultivation in the European Union, one of which has been withdrawn. Unable to
define GM crops satisfactorily, the European Commission has fallen back on a
definition based on process. The shortcomings of this approach are all too clear
as the Commission grapples with the advent of genome editing. This has led to a
long and damaging delay in the Commission issuing an opinion on how genome-edited
crops should be regulated. At the same time, national bans imposed by member
states on GM crops without any evidence of safety concerns have been legalized.
The Commission also faces the prospect of assessing an increasing number of GM
and genome-edited crops with deliberately altered composition. In this article,
the operation of regulations covering GM crops in the European Union and the
effect they have had on the development of plant biotechnology are reviewed,
while the issues raised by new technologies are discussed. It is argued that
there is an urgent need for the European Union to shift its position on plant
biotechnology if agriculture is to meet the challenges of coming decades. (c)
2018 The Author. Journal of the Science of Food and Agriculture published by John
Wiley & Sons Ltd on behalf of Society of Chemical Industry.
PMID- 29952141
TI - Relative bioavailability of bedaquiline tablets suspended in water: Implications
for dosing in children.
AB - AIMS: Bedaquiline is an important novel drug for treatment of multidrug-resistant
tuberculosis, but no paediatric formulation is yet available. This work aimed to
explore the possibility of using the existing tablet formulation in children by
evaluating the relative bioavailability, short-term safety, acceptability and
palatability of suspended bedaquiline tablets compared to whole tablets. METHODS:
A randomized, open-label, two-period cross-over study was conducted in 24 healthy
adult volunteers. Rich pharmacokinetic sampling over 48 h was conducted at two
occasions 14 days apart in each participant after administration of 400 mg
bedaquiline (whole or suspended in water). The pharmacokinetic data were analysed
with nonlinear mixed-effects modelling. A questionnaire was used to assess
palatability and acceptability. RESULTS: There was no statistically significant
difference in the bioavailability of the suspended bedaquiline tables compared to
whole. The nonparametric 95% confidence interval of the relative bioavailability
of suspended bedaquiline tablets was 94-108% of that of whole bedaquiline
tablets; hence, the predefined bioequivalence criteria were fulfilled. There were
no Grade 3 or 4 or serious treatment emergent adverse events recorded in the
study and no apparent differences between whole tablets and suspension regarding
taste, texture or smell. CONCLUSIONS: The bioavailability of bedaquiline tablets
suspended in water was the same as for tablets swallowed whole and the suspension
was well tolerated. This suggests that the currently available bedaquiline
formulation could be used to treat multidrug-resistant tuberculosis in children,
to bridge the gap between when paediatric dosing regimens have been established
and when a paediatric dispersible formulation is routinely available.
PMID- 29952142
TI - Gastrointestinal: Wrong connection: An infected mediastinal pseudocyst
complicating disconnected duct syndrome.
PMID- 29952143
TI - Bullying and alexithymia: Are there differences between traditional, cyber,
combined bullies, and nonbullies in reading their own emotions?
AB - BACKGROUND: Few studies have examined alexithymia, the inability to identify or
describe one's emotions, as a possible correlate of bullying. AIMS: To
investigate whether there are differences among 12-18 year-olds in capacity for
identifying and/or describing own emotions between traditional bullies, cyber
bullies, combined bullies, and nonbullies. METHODS: Data from self-report
questionnaires completed by 897 female and 652 male 12-18 year-olds (mean 14.5
years, standard deviation 1.68) from Germany and Thailand were analysed using
analysis of covariance. RESULTS: Young people who reported never having bullied
others scored lower on the alexithymia scale than traditional, cyber, or combined
bullies. There were no differences between traditional and cyber bullies on this
measure, but those who operated in both ways had significantly higher alexithymia
scores compared with those who bullied in just one modality. CONCLUSION:
Alexithymia is thus likely to be an important factor to consider in prevention
and treatment of bullying. We recommend that prevention programmes include
elements to help identify and describe one's own emotions, providing additional
support, and "training" if alexithymia is identified. When young people use cyber
techniques and traditional bullying methods, it seems likely that they will have
greatest need in this respect.
PMID- 29952144
TI - Epidural Electrotherapy for Epilepsy.
AB - Penetrating electronics have been used for treating epilepsy, yet their
therapeutic effects are debated largely due to the lack of a large-scale, real
time, and safe recording/stimulation. Here, the proposed technology integrates
ultrathin epidural electronics into an electrocorticography array, therein
simultaneously sampling brain signals in a large area for diagnostic purposes and
delivering electrical pulses for treatment. The system is empirically tested to
record the ictal-like activities of the thalamocortical network in vitro and in
vivo using the epidural electronics. Also, it is newly demonstrated that the
electronics selectively diminish epileptiform activities, but not normal signal
transduction, in live animals. It is proposed that this technology heralds a new
generation of diagnostic and therapeutic brain-machine interfaces. Such an
electronic system can be applicable for several brain diseases such as tinnitus,
Parkinson's disease, Huntington's disease, depression, and schizophrenia.
PMID- 29952145
TI - Trends in rates of inpatients treated for testicular cancer in France, 2000-2014.
AB - Testicular cancer is rare, accounting for 1-3% of incidence of all malignancies
in men. Forecasts predict that the incidence of testicular cancer will increase
by 25% in Europe by 2025. We aimed to describe temporal and spatial trends of
rates of patients surgically treated for testicular cancer (STTC) in France over
the period 2000-2014. Using the International Classification of Diseases and
medical procedure codes, from the national hospital discharge database, we
selected patients diagnosed with testicular cancer during 2000-2014 who underwent
surgery. We used the world's standard population as a reference to standardize
rates. We included 29,760 STTC patients. The mean age at diagnosis was 37.4 (+/
13.5) years. Over the period 2000-2014, the standardized incidence rate of STTC
was 6.2 [95% CI: 6.1;6.3] per 100,000 person-years. The overall rate of STTC
increased by 21.3% between 2000 and 2014. The annual percentage change (APC) was
+1.9% [95% CI: 1.4;2.3] over that period. The incidence rate of STTC was highest
among men aged 30-44 (15.0 [95% IC: 14.7;15.2] per 100,000 person-years) and
lowest among men aged 0-14 (0.2 [95% IC: 0.16;0.22]). Age-specific STTC incidence
rates were similar to indicators from cancer registry data except in elderly men
aged 60 years and over. Over the study period, the incidence of STTC increased
over the year in all the regions of Metropolitan France. APC varied across
regions from 1.0% [95% IC: -4.1;6.1] in Ile-de-France to 4.2% [95% IC: -0.8;9.2]
in Corse. Hospital discharge data, which are more quickly available than
population-based data, are good complementary surveillance source for monitoring
testicular cancer, especially in young adult patients and area without population
based registry.
PMID- 29952146
TI - Calreticulin promotes proliferation and extracellular matrix expression through
Notch pathway in cardiac fibroblasts.
AB - BACKGROUND: Cardiac fibrosis is one of the most important underlying causes of
several cardiac diseases. The role of calreticulin (CRT) in cardiac diseases has
already been established. The overor under-expression of CRT can lead to cardiac
diseases. OBJECTIVES: This study was aimed to explore the effect of CRT on
cardiac fibrosis and also to investigate the possible underlying molecular
mechanism. MATERIAL AND METHODS: Human cardiac fibroblast cells (HCF) were used
in the experiment. The cells were transfected with the CRT expression vector
constructed by sub-cloning the full-length wild-type CRT coding sequence into
pcDNA3.1 (pc-CRT group), empty construct pcDNA3.1 (pcDNA3.1 group), CRT-specific
siRNA (si-CRT), and si-NC (negative control). The Cell Counting Kit-8 (CCK-8)
assay, apoptosis assay and invasion assay were performed. Quantitative real time
polymerase chain reaction (qRT PCR) and western blot analysis were performed to
measure the expressions of different mRNAs and proteins. RESULTS: The CRT
expression was significantly increased (p < 0.01) and decreased (p < 0.01) in the
pc-CRT and si-CRT groups, respectively. The CRT over-expression led to increased
cell viability and invasiveness (p < 0.05) and a decreased percentage of
apoptotic cells. The over-expression of CRT led to a significant increase in the
expressions of collagen (I and III) (p < 0.01) and matrix metalloproteinases (MMP
2 and 9) (p < 0.05). The Notch pathway was also significantly activated (p <
0.05) by the over-expression of CRT and vice versa when suppressed. CONCLUSIONS:
The results showed that the CRT over-expression was associated with increased
cell viability and invasiveness and decreased apoptosis, and the activation of
the Notch pathway in HCF, which suggests its possible implication in CRT-induced
cardiac fibrosis.
PMID- 29952147
TI - Examination of the antioxidant effects of pre-HSG melatonin use on ovarian
surface epithelium in rats: An experimental study.
AB - BACKGROUND: There is no study of whether the dysplastic changes in the ovarian
surface epithelium of X-ray-exposed rats during hysterosalpingography (HSG)
decrease or not with the use of Lipiodol and melatonin given both
intraperitoneally (i.p.) and into the suspensorium ovarii. OBJECTIVES: We
investigated the restorative effects of melatonin and Lipiodol administration
during the HSG procedure on the dysplastic changes in the ovarian surface
epithelium of X-ray-exposed rats. MATERIAL AND METHODS: A total of 50 Wistar rats
with regular estrous cycles were randomly divided into 5 groups. Group 1 was the
control group. In other groups, X-ray was applied (group 2), 0.1 mL Lipiodol was
applied to each uterine horn (group 3), 20 mg/kg intraperitoneal melatonin
application was followed by 0.1 mL Lipiodol administration to each uterine horn
after 15 min (group 4), and 20 mg/kg melatonin was administered to the ligamentum
suspensorium ovarii, followed by 0.1 mL Lipiodol application to each uterine horn
after 15 min (group 5). The rats in groups 2-5 were exposed to whole body
radiation 3 times. After 3 h, the abdomens of all rats were reopened and left
oophorectomy was performed. RESULTS: The presence of nucleoli and mitosis values
were found similar among the groups. All other parameters were significantly
higher in group 2 compared to other groups, except for the presence of nucleoli
and mitosis values (p < 0.05). The presence of hyperchromasia and the total score
were found to be the highest in group 2, followed by group 3, when compared to
other groups (p < 0.05). It was detected that the detrimental effects of X-ray
exposure diminished with Lipiodol use, and were further reduced by the use of
melatonin in combination. CONCLUSIONS: We suggest that the use of melatonin and
Lipiodol during HSG may prevent the carcinogenic changes exerted by radiation on
the ovarian surface epithelium.
PMID- 29952148
TI - The expression of marker genes during the differentiation of mesenchymal stromal
cells.
AB - Mesenchymal stromal cells (MSCs) are an excellent and easily accessible source of
precursor cells that have applications in regenerative medicine. They can be
obtained from almost any tissue; however, bone marrow, Wharton's jelly and
adipose tissue are the most frequently used sources of MSCs. Increased interest
in using MSCs in medical procedures has resulted in a pressing need to identify
the genetic elements that can indicate the presence and the characteristics of
MSCs. Genomic profiling enables the identification and characterization of MSCs
as well as finding biomarkers and key molecules involved in all processes
occurring in the cell. This knowledge is essential for developing a stem cell
approach for tissue engineering and can improve the development of new clinical
applications of MSCs. This review is an attempt to give an overview of key
genetic markers indicating the main directions of MSC differentiation. The
expression of these genes provides information about the direction and progress
of differentiation and about interactions with the surrounding environment as
well as specific molecular pathways that MSCs are involved in.
PMID- 29952150
TI - Pathophysiology and nursing management of acute pancreatitis.
AB - Acute pancreatitis is a potentially life-threatening condition primarily
associated with gallstones or prolonged and excessive alcohol intake. Although
the initial triggers of the condition can vary, the resulting pathophysiology is
broadly similar irrespective of the cause. This article explores the
pathophysiology of the main causes of acute pancreatitis, and discusses nursing
management of the condition in the acute setting and the long-term issues to
consider. It also outlines the conservative management of the condition, which
includes pain management, provision of fluids and nutritional care. In the
management of acute pancreatitis, nursing care can often overlap with medical
management, especially as the condition deteriorates. Therefore, it is important
that nurses develop comprehensive knowledge of the management of acute
pancreatitis.
PMID- 29952149
TI - Quantitative analysis of mitoflash excited by femtosecond laser.
AB - Mitochondrial oxidative flashes (mitoflashes) are oxidative burst events in
mitochondria. It is crosslinked with numerous mitochondrial molecular processes
and related with pivotal cell functions such as apoptosis and respiration. In
previous research, mitoflashes were found as spontaneous occasional events. It
would be observed more frequently if cells were treated with proapoptotic
chemicals. We show that multiple mitoflashes can be initiated by a single
femtosecond-laser stimulation that was tightly focused on a diffraction-limited
spot in the mitochondrial tubular structure. The mitoflash events triggered by
different photostimulations are quantified and analyzed. The width and amplitude
of mitoflashes are found very sensitive to stimulation parameters including laser
power, exposure duration, and total incident laser energy. This study provides a
quantitative investigation on the photostimulated mitoflashes. It may thus
demonstrate such optical method to be a promising technique in future
mitochondrial research.
PMID- 29952151
TI - [in process]
PMID- 29952152
TI - [in process]
PMID- 29952153
TI - [in process]
PMID- 29952154
TI - [in process]
PMID- 29952155
TI - [in process]
PMID- 29952156
TI - [in process].
PMID- 29952157
TI - Evidence-based position paper on Physical and Rehabilitation Medicine (PRM)
professional practice for persons with spinal cord injury. The European PRM
position (UEMS PRM Section).
AB - INTRODUCTION: Spinal cord injury (SCI) is a devastating condition and a challenge
for every health system and every society. This EBPP represents the official
position of the European Union through the UEMS PRM Section and designates the
professional role of PRM physicians for people with SCI. The aim of the paper was
to improve Physical and Rehabilitation Medicine (PRM) physicians' professional
practice for persons with SCI in order to improve their functionality, social and
community reintegration, and to overcome activity limitations and/or
participation restrictions. EVIDENCE ACQUISITION: A systematic review of the
literature and a consensus procedure by means of a Delphi process have been
performed involving the delegates of all European countries represented in the
UEMS PRM Section. EVIDENCE SYNTHESIS: The systematic literature review is
reported together with thirty-eight recommendations resulting from the Delphi
procedure. CONCLUSIONS: The professional role of PRM physicians who have
expertise in the rehabilitation of SCI is to run rehabilitation programmes in
multi-professional teams, working in an interdisciplinary way in a variety of
settings to improve the functioning of people with SCI.
PMID- 29952158
TI - [in Process].
PMID- 29952159
TI - Improvement of arterial wall phenotype in subjects at moderate cardiovascular
risk induced by very low-dose fluvastatin/valsartan combination: a pilot study.
AB - BACKGROUND: The largest population that suffers from cardiovascular events are
subjects at moderate cardiovascular risk. However, no effective and safe
preventive treatment is available for this population. We investigated whether
their arterial wall phenotype could be turned to a lower risk direction by low
dose fluvastatin/valsartan combination (low-flu/val). METHODS: Twenty males at
moderate cardiovascular risk (as classified by SCORE) were blindly randomized
into the intervention group (N.=10, low-flu/val: 10 mg/20 mg) or control group
(N.=10, placebo). At inclusion and after 30 days of treatment, brachial flow
mediated dilatation (FMD), beta-stiffness coefficient, carotid pulse wave
velocity (c-PWV), carotid-femoral PWV, Reactive Hyperemia Index, high-sensitivity
C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1,
total antioxidant status and expression of several protective genes (SIRT1, mTOR,
NF-kappaB1, NFE2L2, PRKAA1) were followed. RESULTS: Treatment resulted in
improved FMD (from 3% to 4.2%, P=0.008), c-PWV (from 6.7 to 6.2 m/s, P=0.006), hs
CRP (from 5.39 to 3.35 mg/L, P=0.041) and SIRT1 expression (3.34-fold difference,
P=0.047). No other vascular, inflammation and genetic parameters changed. The hs
CRP values after intervention correlated significantly with SIRT1 expression. The
improved FMD persisted even 10 weeks after treatment discontinuation. The
obtained changes were not followed by changes of lipids or blood pressure.
Overall, the results revealed improvement in three different, although
interrelated preventive arterial wall characteristics. CONCLUSIONS: This pilot
study revealed that intervention with low-flu/val importantly shifts the arterial
wall phenotype in a lower risk direction. This improvement could be interpolated
into clinical benefits that remain to be further studied.
PMID- 29952160
TI - [in process].
PMID- 29952161
TI - Virus-free and cured? The "ART" of adherence. Current efficacy of anti-HIV
therapy.
AB - The antiretroviral therapy (ART) enables an almost normal life with HIV
infection. Does this also hold true for sexual intercourse, i.e. safe sex without
condoms? The European PARTNER-study provides evidence for a very low risk of
transmission for condomless sex under optimized conditions such as early,
adherent and lasting ART (<200 RNA copies/ml) as well as stable partnerships. The
risk of transmission is enhanced with non-compliance or shortlasting (< 6 months)
ART, increased HIV-1 RNA load and frequent partnerships.
PMID- 29952162
TI - Hepatitis C treatment - yesterday, tomorrow and ...
AB - During the last years, treatment of chronic hepatitis C virus infection (HCV) was
characterized by the development of new therapeutic agents and their combined
use. By now the problem of treating HCV seems to be largely solved. The broad
range of available therapeutics has the potential to enable a complete cure of
this liver disease, which is associated with many complications, thus providing
also economic benefits.
PMID- 29952163
TI - Tropical viruses approaching Europe.
AB - During the last years, headlines about the advance of tropical infectious
diseases, which are transmitted by mosquitos, become more frequent. Some of these
mosquitos are classified as invasive species in Europe. The World Health
Organization (WHO) and the European Center for Disease Prevention and Control
(ECDC) are enhancing the observation of the geographical spread of these species.
Especially the Asian tiger mosquito and the Yellow fever mosquito are in focus.
In Germany the vector competency of domestic mosquito species is investigated.
PMID- 29952164
TI - Tropical viruses approaching Europe.
AB - During the last years, headlines about the advance of tropical infectious
diseases, which are transmitted by mosquitos, become more frequent. Some of these
mosquitos are classified as invasive species in Europe. The World Health
Organization (WHO) and the European Center for Disease Prevention and Control
(ECDC) are enhancing the observation of the geographical spread of these species.
Especially the Asian tiger mosquito and the Yellow fever mosquito are in focus.
In Germany the vector competency of domestic mosquito species is investigated.
PMID- 29952166
TI - Change in Overweight from Childhood to Early Adulthood and Risk of Type 2
Diabetes.
PMID- 29952165
TI - Neuroenhancement and mood enhancement - Physiological and pharmacodynamical
background.
AB - Pharmacological neuroenhancement and mood enhancement are gaining tremendous
importance in society. The main motivation for neuroenhancement and mood
enhancement is the anticipated increase in attention and vigilance, better
performance in learning and memory and mood stability to meet the complex demands
of an exacerbating meritocracy. Most users apply drugs originally designated for
attention disorders, sleep disorders or dementia. Application of related drugs in
terms of enhancement strategies in healthy individuals is off-label per se, the
acquisition and distribution illegal. Here, we first provide an overview of the
basic physiological mechanisms underlying vigilance, learning and memory, and
emotional states. We then present the different pharmacological classes, i. a.
purines and methylxanthines, phenylethylamine, modafinil, nootropics and
antidepressants and elaborate their pharmacodynamics profile. Special attention
will be paid to the norepinephrine/dopamine and cholinergic receptors and
transporter systems but also to functional interaction with adenosine, serotonine
and the glutamate receptor systems. Metaanalysis revealed that efficacy reported
in, e. g. ADHD or dementia patients cannot be translated to healthy individuals.
A validated positive effect on attention and vigilance has only been reported for
some phenylethylamines and modafinil. It is likely that new developments,
particularly in the field of antidementives will dramatically enhance
neuroenhancement and mood enhancement. Drug regulatory actions, public and
political discussions are necessary to meet the ethical and legal challenges of
neuroenhancement and mood enhancement in the future.
PMID- 29952167
TI - Stroke prevention in atrial fibrillation - latest guideline recommendations and
real world data.
AB - Atrial fibrillation (AF) occurs with a prevalence of 1 % in the general
population, up to 8 % in patients over 80 years of age and can lead to
palpitations, tachycardia, hospitalization for heart failure and stroke. In order
to prevent strokes, oral anticoagulation is necessary. In the 2016 guidelines for
the management of atrial fibrillation, non vitamin K anticoagulants (NOACs) are
preferred among vitamin K anticoagulants due to less severe bleeding, especially
intracranial haemorrhage. There is also no longer evidence for antiplatelet
therapy in AF. Apart from randomized controlled trials it has been shown in real
world data that use of NOACs is safe and feasible. NOACs are not indicated in
patients with mechanical valve replacement and valvular atrial fibrillation.
Since November 2015 the first specific antidote for dabigatran is available in
Germany, a factor Xa antidote (apixaban, rivaroxaban, edoxaban) is being tested
in a phase III study.
PMID- 29952168
TI - Change in Overweight from Childhood to Early Adulthood and Risk of Type 2
Diabetes.
PMID- 29952169
TI - [in process].
PMID- 29952170
TI - Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection.
PMID- 29952171
TI - Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection.
PMID- 29952172
TI - ROBINS-1: A tool for asssessing risk of bias in non-randomised studies of
interventions.
AB - Compared to randomized controlled trials, non-randomized studies of interventions
might be biased in additional domains. As most previous tools for assessing risk
of bias are not sufficient, a Cochrane working group has developed a new risk of
bias tool called ROBINS-I (Risk of bias in non-randomized studies of
interventions).
PMID- 29952173
TI - Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection.
PMID- 29952174
TI - Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection.
PMID- 29952175
TI - Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection.
PMID- 29952176
TI - The effect of jazz dance on physical and mental health of students with different
physical fitness: a randomized controlled trial.
AB - BACKGROUND: The physical and mental health of college students tends to
continuously decline worldwide. Thus, improving their health is necessary. Jazz
dance may be one of the effective exercises to improve one's health. However, the
effect of jazz dance exercise on different physical fitness level and whether the
intensity of jazz dance exercises can improve physical and mental health
simultaneously and efficiently need to be investigated. In this study, we
systematically assessed the effect of jazz dance on physical and mental health of
college students by a rigorous randomized, parallel-controlled design. METHODS:
An experimental study including 90 Chinese female college students (junior and
senior) was performed. They completed an 8-week jazz dance class (two times/week
for 70 min per session). Data on psychological status were obtained using the
Subjective Exercise Experiences Scale after every class. Based on the Japanese
national physical fitness test method, we identified the body weight and body
mass index and the students performed 30-s sit ups, standing long jump, 20s
repeated across the body, and seated forward flexion to determine their physical
fitness at baseline and after 8 weeks. Repeated measures analyses of variance and
paired samples t-tests were used to compare the means of the participants' data.
RESULTS: Differences in the mean of mental health scores over time were
significant and showed an increasing trend (p<0.005) in all groups. Physical
fitness showed an increasing trend in the low fitness level group. Most of the
variables decreased slightly in the high fitness level group; however,
flexibility significantly decreased. CONCLUSIONS: Among the participants with
different physical fitness, a similar training has different training effects.
This study demonstrates that appropriate training intensity and content are vital
to improve physical and mental health.
PMID- 29952177
TI - Incidence and conditions of musculoskeletal injuries in elite Spanish tennis
academies: a prospective study.
AB - BACKGROUND: Injuries are a major adverse event in a tennis player's career.
Reducing injury requires a thorough knowledge of the epidemiology of tennis
injuries. The aim of this study was to report the incidence and conditions of
musculoskeletal injuries in elite tennis players. METHODS: The medical staff of
162 tennis players recorded the type and conditions of musculoskeletal injuries
for one season in accordance with a consensus statement. Other information such a
training hours and competitive games played was also recorded. RESULTS: A total
of 199 injuries were recorded, equivalent to an overall incidence of 1.03
injuries per 1000 played games and 1.25 per 1000 h of training. Lower limbs were
the most common injury location in male players (38.3%) and the trunk in females
(41.3%) although muscle/tendon injuries were the most common type in both groups.
There was a higher percentage of gradual-onset injuries (61.4%) than acute
injuries (38.6%). The injury incidence on clay courts was 1.53+/-2.85 and 1.11+/
1.29 injuries per 1000 played games in males and females, respectively. The
majority of the gradual- onset injuries were reported in the upper limbs (45.9%)
while acute injuries were mostly located in the lower limbs (68.8%). During match
exposure, the trunk was the most common location of injury (36.8%) while the
lower limbs were the most common location of injury during training (41.7%).
CONCLUSIONS: In elite tennis, a high percentage of musculoskeletal injuries were
located in the lower limbs in males and in the trunk in females, occurred during
matches and affected muscles or tendon structures. However, the type of the
injury is influenced by different conditions such as the type of exposure (match
vs. training) or the mechanism of injury (acute vs. gradual-onset). This
information suggests that an early focus should be placed on the monitoring of
the workload and changes in court surface during a season.
PMID- 29952178
TI - Changes in hormone levels of participants in a 622-km ultramarathon race based on
distance and recovery period.
AB - BACKGROUND: Runners who participate in endurance sports such as marathons or
ultramarathons have superior physical capabilities and health benefits compared
to others. However, they may suffer long-term effects of the negative
physiological changes during long-distance running. This study aimed to examine
the effects of an ultramarathon on hormone levels, and the associated risks.
METHODS: Ten participants who completed a 622-km ultramarathon were included.
Blood was collected pre-race, at the 300-km mark, the 622-km mark, and on the 3rd
day of recovery (RD3) and the 6th day of recovery (RD6) and analyzed for human
growth hormone (HGH), cortisol, beta-endorphin, serotonin, testosterone,
luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. RESULTS:
HGH and beta-endorphin showed the highest increase at the 300-km mark compared to
pre-race levels, with recovery on RD3 and RD6, respectively. LH, cortisol, and
serotonin showed the highest levels of increase at the 622-km mark, with recovery
on RD6 for LH, and RD3 for cortisol and serotonin. FSH showed the highest level
of decrease at both 300-km and 622-km marks compared to pre-race levels, with
recovery on RD3. Testosterone decreased the most at the 300-km mark compared to
the pre-race level and this decrease was below the normal levels; however, it
recovered to normal levels on RD3. CONCLUSIONS: Hormone levels after the 622-km
ultramarathon were within their normal ranges, except for testosterone. However,
all the hormones recovered to pre-race levels on RD3 or RD6. This study showed
that running ultramarathons does not cause abnormal hormone levels.
PMID- 29952179
TI - The effect of a concentrated period of soccer specific fitness training with
small-sided games on physical fitness in youth players.
AB - BACKGROUND: It is unknown whether a concentrated period of small-sided games and
high intensity training is an effective training approach in youth soccer
players. The aim of the study was to examine the effect of a concentrated period
of soccer specific training on physical fitness in youth players. METHODS:
Nineteen male soccer players, from two teams, participated (mean +/- SD age: 16.2
+/- 0.8 years; body mass: 58.2 +/- 7.6 kg; height: 170.8 +/- 7.7 cm). One team
performed 5 days of small-sided games and high intensity training (SSG & HIT; n =
12) and the other team regular soccer training with 1 day of SSG and HIT (REG; n
= 7) weekly for 4 weeks. The 30-15 intermittent fitness test (30-15 IFT),
countermovement jump (CMJ) and change of direction (COD) performance were
measured pre and post intervention. Heart rate (HR) and rating of perceived
exertion (RPE) were recorded and session load calculated (RPE x minutes).
RESULTS: Average % of maximum HR and session load were 83% and 344 AU for the SSG
& HIT vs 73% and 253 AU for the REG (P< 0.05). 30-15 IFT improved for the SSG &
HIT (from 17.0 +/- 1.1 to 18.4 +/- 0.8 km/h; p< 0.05; ES = 0.57) with no
difference for the REG group (Pre: 17.9 +/- 1.3, Post: 18.2 +/- 1.6 km/h, ES=
0.10). CMJ and COD were unchanged in both groups and no injuries were reported.
CONCLUSIONS: A 4-week concentrated period of daily SSG & HIT is effective for
improving endurance performance in youth soccer players. This was without
injuries and without negating performance in power and change of direction.
PMID- 29952180
TI - Apalutamide and Metastasis-free Survival in Prostate Cancer.
PMID- 29952181
TI - Autoimmune Polyendocrine Syndromes.
PMID- 29952182
TI - [In process].
PMID- 29952183
TI - Autoimmune Polyendocrine Syndromes.
PMID- 29952184
TI - Case 5-2018: A Man with Confusion after Stem-Cell Transplantation.
PMID- 29952185
TI - Accuracy of Post-Void Residual Urine Volume Measurement Using an Ultrasound
Bladder Scanner among Postoperative Radical Hysterectomy Patients.
AB - Background: Postoperative urinary retention occurs in 17 to 42% of Radical
hysterectomy (RH) cases. The gold standardassessment of post-void residual urine
volume (PVR) is bladder catheterization. The use of the 3D portable ultrasound
device (VerathonBladderScan BVI 9400) to evaluate PVR is quick, safe, non
invasive, painless, and comfortable for patients as well as being easy to use.
Objective: To compare the accuracy of ultrasound bladder scanner with that of
urethral catheterization in the assessment of post-void residual urine volume
(PVR). Material and Method: This was a prospective study. After removal of
Foley's catheter in postoperative radical hysterectomy(RH) patients, the voiding
care schedule consisted of voids after six hours or earlier if the patient had
the urge. Promptly after voiding, PVR was measured using the BladderScan (Scan
volume). Immediately after the procedure, urethral catheterization was performed
to obtain the actual PVR (Catheter volume). The process was repeated in
subsequent voids, and correlations between scan volume and catheter volume were
analyzed. Results: Seventy patients (140 measurements) were included. A high
correlation was found between the scan volume and the catheter volume (r = 0.89,
p<0.001). A 91.0% specificity and 93.1% negative predictive value(NPV) were
obtained using the scan volume in predicting a catheter volume of <100 ml. The
difference in measurements between the two methods was not related to age, body
mass index, parity, co-existing illness, type of surgical incision or duration of
indwelling catheter. When catheter volume >100 ml was the cutoff for determining
the need for re-catheterization, the scan volume returned 90.0% accuracy.
Repetition of ultrasound scan in patients who had a first scan volume of <100 ml
yielded a 97.2% specificity and 100% NPV in predicting catheter volume of <100
ml. Conclusion: The Bladder Scan provides good correlation together with high
rates of specificity and NPV, and it could be an alternative modality to
catheterization for the measurement of PVR in postoperative RH patients.
PMID- 29952186
TI - Intrauterine Adhesions: Causes and Treatment Outcomes among Thai Women
AB - Objective: To explore the causes and treatment outcomes of intrauterine adhesions
among Thai women. Material and Method: This retrospective cross-sectional study
recorded and analyzed the demographic data, causes, and treatment outcomes of 75
patients who underwent hysteroscopic adhesiolysis between January 2004 and June
2015 at Maharaj Nakhon Chiang Mai Hospital, Chiang Mai, Thailand. Results: The
most common etiology of intrauterine adhesions was a history of early pregnancy
termination by curettage (68%). Sixty-nine percent of the patients had menstrual
abnormalities. Twenty-two percent of the patients had severe adhesions.
Tuberculous endometritis caused the most severe case. Sharp hysteroscopic
adhesiolysis improved the condition in 77.7% of the patients. The outcomes of the
patients with mild to moderate IUA were better than those with severe
intrauterine adhesions (88.2% vs. 43.8%, respectively) (p = 0.001). Fifty-one
patients planned to conceive, and 49% succeeded after hysteroscopic surgery.
Conclusion: Menstrual abnormalities were the most common presentation of
intrauterine adhesions. The most common cause of intrauterine adhesions was early
pregnancy termination by curettage. However, tuberculosis endometritis caused the
most severe case. Hysteroscopic adhesiolysis significantly improves menstrual
function and fertility outcomes; mild to moderate cases have a better prognosis.
PMID- 29952187
TI - [In Process].
PMID- 29952188
TI - [In process].
PMID- 29952189
TI - A Prospective Randomized Controlled Trial Comparing Posterolateral Lumbar Fusion
With and Without Bone Marrow Concentrate Augmentation in Single-Level Lumbar
Spondylolisthesis.
AB - Background: Bone marrow (BM), which is a good source of stem cells and biological
factors, has the potential to enhance bone fusion. Simple centrifugation
technique is one of the procedures used to concentrate BM aspirate for increasing
number of cells. However, there are limited clinical study for using BM
concentrate augmentation in spinal fusion. Objective: This study was designed to
examine the spinal fusion enhancement effects of bone marrow (BM) concentrate
augmentation on poster lateral lumbar fusion (PLF) with autologous local bone
graft in terms of both quality and quantity, as compared with a control procedure
without BM concentrate augmentation. Material and Method: Twelve patients with L4
L5 spondylolisthesis scheduled for PLF after decompressive laminectomy and
pedicle screw instrumentation were included in this study. This prospective
randomized controlled trial was conducted at Siriraj Hospital during the 2009 to
2012 study period. Patients were randomly assigned to two groups. One group
underwent PLF with local bone graft with BM concentrate augmentation (BM group)
and the other group underwent PLF with local bone graft only (non-BM group).
Clinical outcomes were evaluated by the Oswestry Disability Index (ODI)
preoperatively and at 3 and 6 months after PLF. Bone fusion quality was evaluated
by bony bridging on 3D-CT imaging. Fusion mass volumes were measured on
quantitative 3D-CT scans at 1 week and 6 months, postoperatively. Results:
Clinical outcome scores did not differ between groups. Six-month postoperative 3D
CT imaging showed complete PLF bridging in 58.3% and 100% of patients in the BM
and non-BM groups, respectively. PLF mass volumes were decreased at 6 months by
51.1% in the BM group and by 48.5% in the non-BM group. One patient in the BM
group had local inflammation at the BM aspiration site. Conclusion: Bone marrow
concentrate augmentation in this small randomized controlled trial failed to
demonstrate positive effects on autologous local bone graft in posterolateral
lumbar fusion relative to both quality and quantity. The high percentage of
incomplete bridging should also be noted and further investigated.
PMID- 29952190
TI - Clinical Effectiveness and Safety of Microdecompression in Thai Lumbar Spinal
Stenosis Patients.
AB - Background: Microdecompression (MD) is a minimally invasive spine surgery for
lumbar spinal stenosis (LSS). However, there was no long-term outcome study of
this procedure in Thailand. Objective: The aim of this study was to evaluate the
safety, complications, and surgical outcomes in Thai patients whounderwent MD for
LSS. Material and Method: A single-institution database was reviewed for Thai
patients with LSS who underwent MD during the 2005 to 2014 study period. We
analyzed demographic data and clinical data, intraoperative and postoperative
data, and immediate complications. Oswestry Low Back Disability Index (ODI) and
EQ-5D-5L were used to measure outcomes. Results: Seventy patients were enrolled
(43 female and 27 male), with an average age of 64.1+10.6 years. Mean operative
time was 99.5+31.6 minutes per level. Average length of stay was 5.2+2.8 days.
Estimated blood loss was 90.5+65.6 ml. The most common level was L4-5. The
average follow-up was 47.5+33.8 months. All postoperative patient-reported
outcome measures were statistically significantly improved compared to
preoperative measures (p<0.05). Average preoperative and postoperative ODI score
was 60.8+20.6 and 15.9+15.7, respectively. Average pre-operative and
postoperative EQ-5D-5L scores were 35.2+23.4 and 92.2+10, respectively. Immediate
complications were found in 7 patients, including 5 incidentaldural tear, 1
epidural hematoma, and 1 superficial wound infection. Late complications were
found in 5 patients, including 1 cerebrospinal fluid leakage and 4 additional
fusion surgeries. Of note, 14 patients had grade I degenerative spondylolisthesis
(DS) before surgery although none of these patients complained of significant
back pain. However, 3 of 4 cases that underwent additional fusion had pre
operative DS. Conclusion: Microdecompression surgery was found to be effective
for treating patients with degenerative spinal stenosis. This procedure should be
cautiously used in patients with spondylolisthesis, even in the absence of
significant back pain.
PMID- 29952191
TI - Combined Ilizarov Fixation and Intramedullary Nailing for Treatment of Congenital
Pseudarthrosis of the Tibia.
AB - Background: Congenital pseudarthrosis of the tibia (CPT) is one of the most
challenging conditions in pediatric orthopedics. Multiple objectives must be
achieved to correct this condition successfully, including obtaining union,
prevention of refracture, management of limb-length discrepancy (LLD), and
correction of deformities of the ankle and leg. This combined treatment conjoins
the improved union rate and improved limb-length equalization of Ilizarov
fixation and the controlled alignment and refracture prevention associated within
tramedullary nailing. Objective: To evaluated the outcome of combined Ilizarov
fixation with intramedullary pinning in term of union of pseudathrosis and
residual deformities. Material and Method: Thirteen children who were treated by
this technique were evaluated in this study. Clinical presentation and
radiographs were evaluated and union time, secondary operations and time of
follow-up were recorded. At final follow-up, condition of tibial and fibula
pseudarthrosis, LLD, refracture and deformities of the tibia and ankle were
documented. Results: Union was achieved in 11 children. For the other 2 children,
a secondary procedure using iliac bone graft wasrequired to achieveunion. Fibular
pseudarthrosis persisted in 9 patients. A total of 30 secondary operations were
performed for various indications. At final follow-up, mean anterior bowing was
8.5 degrees (range: 0-20 degrees ), mean medial bowing was 9.5 degrees (range: 0
25 degrees ), and ankle valgus was present in 5 patients. The mean LLD was 1.7 cm
(range: 0-3). Two patients had limping gait. No donor site morbidity was observed
in any patient. Refracture occurred in three cases after nail removal. In these
three cases, secondary operations using the same technique were performed with
favorable outcome. Conclusion: The results of this study demonstrate that
Ilizarov fixation combined with intramedullary nailing is a safe, effective and
practical treatment for management of CPT. This combination technique achieves
multiple objectives including rigid-stable fixation, management of LLD,
correction of residual deformity and prevention of refracture. Moreover, this
technique can be used in cases with previous operations that resulted in
nonunion.
PMID- 29952192
TI - [In process].
PMID- 29952193
TI - [In process].
PMID- 29952194
TI - [In process].
PMID- 29952195
TI - [In process].
PMID- 29952196
TI - Rapid biomarker testing for improved clinical decision-making in nonsmall cell
lung cancer.
PMID- 29952198
TI - How MALDI-TOF MS has changed the microbiology lab.
PMID- 29952197
TI - Clinical labs streamline GI testing with MDx.
PMID- 29952199
TI - Selective Growth Synthesis of Ternary Janus Nanoparticles for Imaging-Guided
Synergistic Chemo- and Photothermal Therapy in the Second NIR Window.
AB - Multifunctional therapeutic agents in the second near-infrared (NIR-II) window
have attracted wide attention on account of their synergetic properties for
effective cancer therapy. Here, we construct a selective growth strategy for the
first time to fabricate ternary Janus nanoparticles (JNPs) containing
hemispherical MnO2 at one side and Au core covered with CuS shell at opposite
side. The obtained ternary JNPs are further modified with poly(ethylene
glycol)thiol to enhance the stability and biocompatibility (designated as PEG-CuS
Au-MnO2 ternary JNPs). The MnO2 domain with mesoporous structures can serve as
hydrophobic drug carriers and magnetic resonance (MR) imaging contrast agents.
Meanwhile, the Au segment is used for X-ray computed tomography (CT) imaging.
Moreover, the PEG-CuS-Au-MnO2 ternary JNPs can conduct hyperthermia at 1064 nm in
NIR-II window to ablate tumors in deep tissue, which is ascribed to the localized
surface plasmon resonance coupling effect of the Au core and CuS domain. All of
the results reveal that PEG-CuS-Au-MnO2 ternary JNPs not only exhibit pre-eminent
CT/MR imaging capabilities, but also provide high chemo-photothermal antitumor
efficacy under the guidance of CT/MR imaging. Taking together, the PEG-CuS-Au
MnO2 ternary JNPs can be regarded as a prospective therapeutic nanoplatform for
dual-modal imaging-guided synergistic chemo-photothermal cancer therapy in the
NIR-II window.
PMID- 29952200
TI - Injectable Gel Constructs with Regenerative and Anti-Infective Dual Effects Based
on Assembled Chitosan Microspheres.
AB - There is increasing demand for biomaterials that both assist with bone
regeneration and have anti-infection qualities in clinical applications. To
achieve this goal, chitosan microspheres with either positive or negative charges
were fabricated and then assembled as a gel for bone healing. The positively
charged chitosan microspheres (CSM; ~35.5 MUm) and negatively charged O
carboxymethyl chitosan microspheres (CMCSM; ~13.5 MUm) were loaded, respectively,
with bone morphogenetic protein (BMP-2) and berberine (Bbr) via swollen
encapsulation and physical adsorption without a significant change in the
electric charges. The release kinetics of BMP-2 and Bbr from the microspheres
were also studied in vitro. The results showed that the Bbr/CMCSM microsphere
group possessed high antibacterial activity against Staphylococcus aureus; the
BMP-2/CSM microsphere group also had excellent cytocompatibility and improved
osteoinductivity with the assistance of BMP-2. The assembled gel group consisting
of Bbr/CMCSM and BMP-2/CSM had a porous structure that allowed biological signal
transfer and tissue infiltration and exhibited significantly enhanced bone
reconstruction compared with that of the respective microsphere groups, which
should result from the osteoconductivity of the porous structure and the
osteoinduction of the BMP-2 growth factor. The oppositely charged microspheres
and their assembled gel provide a promising prospect for making injectable tissue
engineered constructs with regenerative and anti-infective dual effects for
biomedical applications.
PMID- 29952201
TI - Power Dissipation of WSe2 Field-Effect Transistors Probed by Low-Frequency Raman
Thermometry.
AB - The ongoing shrinkage in the size of two-dimensional (2D) electronic circuitry
results in high power densities during device operation, which could cause a
significant temperature rise within 2D channels. One challenge in Raman
thermometry of 2D materials is that the commonly used high-frequency modes do not
precisely represent the temperature rise in some 2D materials because of peak
broadening and intensity weakening at elevated temperatures. In this work, we
show that a low-frequency E2g2 shear mode can be used to accurately extract
temperature and measure thermal boundary conductance (TBC) in back-gated tungsten
diselenide (WSe2) field-effect transistors, whereas the high-frequency peaks
(E2g1 and A1g) fail to provide reliable thermal information. Our calculations
indicate that the broadening of high-frequency Raman-active modes is primarily
driven by anharmonic decay into pairs of longitudinal acoustic phonons, resulting
in a weak coupling with out-of-plane flexural acoustic phonons that are
responsible for the heat transfer to the substrate. We found that the TBC at the
interface of WSe2 and Si/SiO2 substrate is ~16 MW/m2 K, depends on the number of
WSe2 layers, and peaks for 3-4 layer stacks. Furthermore, the TBC to the
substrate is the highest from the layers closest to it, with each additional
layer adding thermal resistance. We conclude that the location where heat
dissipated in a multilayer stack is as important to device reliability as the
total TBC.
PMID- 29952202
TI - From Batch to Continuous Precipitation Polymerization of Thermoresponsive
Microgels.
AB - Microgels are commonly synthesized in batch experiments, yielding quantities
sufficient to perform characterization experiments for physical property studies.
With increasing attention on the application potential of microgels, little
attention is yet paid to the questions (a) whether they can be produced
continuously on a larger scale, (b) whether synthesis routes can be easily
transferred from batch to continuous synthesis, and (c) whether their properties
can be precisely controlled as a function of synthesis parameters under
continuous flow reaction conditions. We present a new continuous synthesis
process of two typical but different microgel systems. Their size, size
distribution, and temperature-responsive behavior are compared in depth to those
of microgels synthesized using batch processes, and the influence of premixing
and surfactant is also investigated. For the surfactant-free poly( N
vinylcaprolactam) and poly( N-isopropylacrylamide) systems, microgels are
systematically smaller, while the actual size is depending on the premixing of
the reaction solutions. However, by the use of a surfactant, the size difference
between batch and continuous preparation diminishes, resulting in equal-sized
microgels. Temperature-induced swelling-deswelling of microgels synthesized under
continuous flow conditions was similar to that of their analogues synthesized
using the batch polymerization process. Additionally, investigation of the
internal microgel structure using static light scattering showed no significant
changes between microgels prepared under batch and continuous conditions. The
work encourages synthesis concepts of sequential chemical conditions in
continuous flow reactors to prepare precisely tuned new microgel systems.
PMID- 29952203
TI - Ultrahigh Conductivity in Two-Dimensional InSe via Remote Doping at Room
Temperature.
AB - Conductivity of two-dimenstional (2D) materials, which largely determines the
efficiency and reliability of nanodevices, is proportional to the product of
carrier concentration and mobility. Conventional doping, such as ionic
substitution or introduction of vacancies, increases carrier concentration and
decreases carrier mobility due to the scattering or trapping of carriers. We
propose a remote-doping strategy that enables the simultaneous enhancement of
both parameters. Density functional theory calculations in 2D InSe reveal that
adsorbing the molecule tetrathiafulvalene (TTF) and applying a 4% external
tensile strain leads to an increase in the carrier concentration of the TTF-InSe
system that is 13 orders of magnitude higher than that of the pristine
counterpart, whereas the carrier mobility is enhanced by 35% compared with the
InSe monolayer. As a consequence of the synergetic role of molecule doping and
strain engineering, ultrahigh conductivity of 1.85 * 105 S/m is achieved in the
TTF-InSe system at room temperature.
PMID- 29952204
TI - Monitoring Neonicotinoid Exposure for Bees in Rural and Peri-urban Areas of the
U.K. during the Transition from Pre- to Post-moratorium.
AB - Concerns regarding the impact of neonicotinoid exposure on bee populations
recently led to an EU-wide moratorium on the use of certain neonicotinoids on
flowering crops. Currently, evidence regarding the impact, if any, the moratorium
has had on bees' exposure is limited. We sampled pollen and nectar from bumblebee
colonies in rural and peri-urban habitats in three U.K. regions: Stirlingshire,
Hertfordshire, and Sussex. Colonies were sampled over three years: prior to the
ban (2013), during the initial implementation when some seed-treated winter-sown
oilseed rape was still grown (2014), and following the ban (2015). To compare
species-level differences, in 2014 only, honeybee colonies in rural habitats were
also sampled. Over half of all samples were found to be contaminated ( n = 408),
with thiamethoxam being the compound detected at the highest concentrations in
honeybee- (up to 2.29 ng/g in nectar in 2014, median <= 0.1 ng/g, n = 79) and
bumblebee-collected pollen and nectar (up to 38.77 ng/g in pollen in 2013, median
<= 0.12 ng/g, n = 76). Honeybees were exposed to higher concentrations of
neonicotinoids than bumblebees in 2014. While neonicotinoid exposure for rural
bumblebees declined post-ban (2015), suggesting a positive impact of the
moratorium, the risk of neonicotinoid exposure for bumblebees in peri-urban
habitats remained largely the same between 2013 and 2015.
PMID- 29952205
TI - Palladium-Catalyzed Regioselective Hydroaminocarbonylation of Alkynes to
alpha,beta-Unsaturated Primary Amides with Ammonium Chloride.
AB - alpha,beta-Unsaturated primary amides have found numerous applications in drug
development, organic materials, and polymer sciences. However, the catalytic
synthesis of alpha,beta-unsaturated primary amides via carbonylation of alkynes
has long been an elusive endeavor. Here, we report a novel palladium-catalyzed
hydroaminocarbonylation of alkynes with NH4Cl as the amine source, enabling the
highly chemo- and regioselective synthesis of alpha,beta-unsaturated primary
amides. A variety of alkynes, including aromatic alkynes, aliphatic alkynes,
terminal alkynes, internal alkynes, as well as diynes with various functional
groups, react well. The method turns the parasitic noncoordination ability of
ammonium salts into a strategic advantage, enabling the gram-scale reaction to be
performed in the presence of 0.05 mol % of catalyst with excellent selectivity.
PMID- 29952206
TI - DNA Logic Operation with Nanopore Decoding To Recognize MicroRNA Patterns in
Small Cell Lung Cancer.
AB - Although DNA computation has traditionally been developed for parallel
calculations in molecular analyses, this approach has recently been considered
for use in diagnostic or medical applications in living systems. In this study,
we propose that the DNA logic operation may be a powerful tool for the
recognition of microRNA patterns, which may have applications for the early
diagnosis of cancers. We developed a rapid, label-free decoding method for output
diagnostic molecules using nanopore measurements. We designed diagnostic DNAs
that autonomously recognized two microRNAs, miR-20a and miR-17-5p, and formed a
four-way junction structure that was captured in the nanopore, showing long
blocking currents. We analyzed the blocking duration based on the central limit
theorem and found that four different operations, i.e., (0, 0), (0, 1), (1, 0),
and (1, 1), could be discriminated. This pattern recognition method has been
differentiated from simple detection methods based on DNA computing and nanopore
technologies.
PMID- 29952207
TI - Polypharmacy involving opioid, psychotropic, and central nervous system
depressant medications, period prevalence and association with suicidal ideation,
active component, U.S. Armed Forces, 2016.
AB - This report uses routinely collected data in the Defense Medical Surveillance
System (DMSS) to explore the period prevalence of polypharmacy among the active
component U.S. military in 2016. The period prevalence across the Department of
Defense was 10.8% and was highest for the Army (14.5%) and lowest for the Marine
Corps (7.4%). Furthermore, a case control study was conducted to explore the
potential association between polypharmacy and incident suicidal ideation (SI).
There was an increased adjusted odds of incident SI within 12 months following
polypharmacy exposure, with adjusted odds ratios ranging from 1.53 (95% CI, 1.38
1.71) to 3.06 (95% CI, 2.00-4.70), depending on the number of qualifying
polypharmacy criteria. Important limitations to the current analysis are
discussed. Results suggest that it would be prudent to screen for SI during the
polypharmacy clinical encounter, particularly for persons with any of the mental
health disorders considered in this report. Inclusion of Department of Defense
Suicide Event Report data along with medically coded SI in future surveillance
would increase the sensitivity of identifying incident cases of SI.
PMID- 29952208
TI - Variations in the incidence and burden of illnesses and injuries among non
retiree service members in the earliest, middle, and last 6 months of their
careers, active component, U.S. Armed Forces, 2000-2015.
AB - This report uses routinely collected data in the Defense Medical Surveillance
System (DMSS) to characterize the incidence and burden of medical conditions
throughout the careers of service members separating from the active component of
the U.S. Armed Forces between 1 October 2014 and 30 September 2015. Three
surveillance periods between 30 September 2000 and 30 September 2015 were defined
by each individual's time in service: early (first 6 months), middle (middle 6
months), and late (last 6 months). Overall, separating service members were most
often aged 25-34 years (59.4%), male (84.0%), non-Hispanic white (64.0%), junior
enlisted (52.4%), in the Marine Corps (33.1%), serving in a repair/engineering
occupation (33.0%), and had never deployed (52.5%). The top five burden of
disease categories across surveillance periods by sex were remarkably similar,
including mental health disorders, which exhibited similar upward trends across
the three surveillance periods (males: 1.3%, 17.0%, and 35.6%; females: 1.8%,
15.1%, and 32.4%, respectively). The most common diagnoses exhibiting upward,
downward, or bimodal trends by incidence rate differences were mental health
disorders, respiratory infections/diseases, and musculoskeletal diseases,
respectively.
PMID- 29952209
TI - Diagnoses of eating disorders, active component service members, U.S. Armed
Forces, 2013-2017.
AB - During 2013-2017, a total of 1,788 active component service members received
incident diagnoses of one of the eating disorders: anorexia nervosa (AN), bulimia
nervosa (BN) or "other/unspecified eating disorder" (OUED). The crude overall
incidence rate of any eating disorder was 2.7 cases per 10,000 person-years. Of
the case-defining diagnoses, OUED and BN accounted for 46.4% and 41.8% of the
total incident cases, respectively. The overall incidence rate of any eating
disorder among women was more than 11 times that among men. Overall rates were
highest among service members in the youngest age groups (29 years or younger).
Crude annual incidence rates of total eating disorders increased steadily between
2013 and 2016, after which rates decreased slightly. Results of the current study
suggest that service members likely experience eating disorders at rates that are
comparable to rates in the general population, and that rates of these disorders
are potentially rising among service members. These findings underscore the need
for appropriate prevention and treatment efforts in this population.
PMID- 29952210
TI - Brief report: Department of Defense midseason vaccine effectiveness estimates for
the 2017-2018 influenza season.
PMID- 29952211
TI - Letter to the Editor.
PMID- 29952212
TI - Ketamine and rapidly acting antidepressants: Breaking the speed of sound or
light?
AB - There is an urgent need for rapidly acting antidepressants. Current therapies
share a delayed onset of action, contrasting with drugs of abuse that have rapid
psychotropic effects but cause tolerance and dependence. A key uncertainty is
whether there is a finite speed limit imposed by the critical role of homeostatic
adaptive mechanisms that underpin the efficacy and onset of available
psychotropic agents and whether this is mutable with emerging agents with
potential rapid onset, in particular ketamine.
PMID- 29952213
TI - Drowning Prevention: Assessment of a Classroom-Based Water Safety Education
Program in Vietnam.
AB - Youth drowning continues to be a primary public health issue globally with
Eurasian countries experiencing some of the highest recorded rates of injury and
death in aquatic settings. The country of Vietnam is currently working toward
reducing the number of youth drowning fatalities. Part of these efforts is the
introduction of an in-school water safety educational program. For this study,
pilot pre/post data were acquired and used to assess overall knowledge
acquisition and changes in knowledge of youth in grades 1 to 5 in central
Vietnam. A total of 229 schools participated, resulting in 40 198 usable surveys.
The results indicated that overall there was a significant change in scores with
an acceptable effect size between measures. Mean scores for each of the water
safety messages were rated as acceptable (above 90%), satisfactory (between 70%
and 90%), and areas of concern (under 70%). Recommendations were made to program
leaders about identified areas of concern.
PMID- 29952214
TI - Osteoplastic Flap Without Obliteration: How I Do It.
AB - Background The osteoplastic flap provides access to pathology of the frontal
sinus and is often performed with obliteration, which can result in significant
long-term complications. Objective To describe the authors' approach to
osteoplastic flap without obliteration. Methods Descriptive analysis. Results
Osteoplastic flap without obliteration preserves frontal sinus function while
permitting direct access to the frontal sinus. In this study, we demonstrate a
combined nonobliterated approach, accessing the frontal sinus with a Draf III
approach to remove a large frontal sinus osteoma. Conclusion The approach
provides excellent exposure for large tumors not otherwise accessible via purely
endoscopic procedures, permits improved surveillance, and minimizes long-term
complications of obliterated sinuses.
PMID- 29952216
TI - Using Patients and Their Caregivers Feedback to Develop ENABLE CHF-PC: An Early
Palliative Care Intervention for Advanced Heart Failure.
AB - OBJECTIVE: Models of early, community-based palliative care for individuals with
New York Heart Association (NYHA) class III/IV heart failure and their families
are lacking. We used the Medical Research Council process of developing complex
interventions to conduct a formative evaluation study to translate an early
palliative care intervention from cancer to heart failure. METHOD: One component
of the parent formative evaluation pilot study was qualitative satisfaction
interviews with 8 patient-caregiver dyad participants who completed Educate,
Nurture, Advise, Before Life Ends Comprehensive Heartcare For Patient and
Caregivers (ENABLE CHF-PC) intervention. The ENABLE CHF-PC consists of an in
person palliative care assessment, weekly telehealth coaching sessions, and
monthly follow-up. Subsequent to completing the coaching sessions, patient and
caregiver participants were interviewed to elicit their experiences with ENABLE
CHF-PC. Digitally recorded interviews were transcribed and analyzed using a
thematic approach. RESULTS: Patients (n = 8) mean age was 67.3, 62.5% were
female, 75% were married/living with a partner; caregivers (n = 8) mean age was
56.8, and 87.5% were female. Four themes related to experiences with ENABLE CHF
PC included "allowed me to vent," "gained perspective," "helped me plan," and
"gained illness management and decision-making skills." Recommendations for
intervention modification included (1) start program at diagnosis, (2) maintain
phone-based approach, and (3) expand topics and modify format. CONCLUSION:
Patients and caregivers unanimously found the intervention to be helpful and
acceptable. After incorporating modifications, ENABLE CHF-PC is currently
undergoing efficacy testing in a large randomized controlled trial.
PMID- 29952217
TI - Supported decision-making from the perspectives of mental health service users,
family members supporting them and mental health practitioners.
AB - BACKGROUND: Supporting the decision-making of mental health service users fulfils
professional, ethical and moral obligations of mental health practitioners. It
may also aid personal recovery. Previous research on the effectiveness of
supported decision-making interventions is limited. AIMS: The study aims to
explore from several perspectives the barriers and facilitators to supported
decision-making in an Australian context. Supported decision-making was
considered in terms of interpersonal experiences and legal supported decision
making mechanisms. METHODS: In all, 90 narrative interviews about experiences of
supported decision-making were conducted and analysed. Participants were mental
health service users who reported diagnoses of schizophrenia, psychosis, bipolar
disorder and severe depression; family members supporting them and mental health
practitioners, including psychiatrists. The data were analysed thematically
across all participants. RESULTS: Negative interpersonal experiences in the
mental health care system undermined involvement in decision-making for people
with psychiatric diagnoses and family carers. Mental health practitioners noted
their own disempowerment in service systems as barriers to good supported
decision-making practices. All groups noted the influence of prevailing attitudes
towards mental health service users and the associated stigma and discrimination
that exist in services and the broader community. They believed that legal
supported decision-making mechanisms facilitate the participation of mental
health service user and their family supporters in supported decision-making.
CONCLUSIONS: Enabling supported decision-making in clinical practice and policy
can be facilitated by (1) support for good communication skills and related
attitudes and practices among mental health practitioners and removing barriers
to their good practice in health and social services and (2) introducing legal
supported decision-making mechanisms.
PMID- 29952215
TI - An Exploratory Study of Washout Rate Analysis for Thallium-201 Single-Photon
Emission Computed Tomography Myocardial Perfusion Imaging Using Cadmium Zinc
Telluride Detectors.
AB - The aim of this study was to assess the washout rate (WOR) for thallium-201
chloride single-photon emission computed tomography (SPECT) myocardial perfusion
imaging (MPI) using cadmium zinc telluride detectors for SPECT (CZT SPECT) versus
conventional Anger-type SPECT (conventional SPECT). A total of 52 Japanese
patients were examined using CZT SPECT and conventional SPECT, and the global
WORs were compared. Additionally, the MPI WORs were compared for patients with a
normal MPI versus those in whom MPI reflected the patients' multivessel disease
(MVD) MPI. Washout rates were similar when approximated by CZT SPECT versus
conventional SPECT 12.59 +/- 2.26%/h vs 12.57 +/- 2.27%/h ( P = .997),
respectively. The WOR values for CZT SPECT versus conventional SPECT were
13.42%/h (1.53%/h) vs 13.93%/h (1.24%/h) ( P = .337), respectively, for 7 normal
MPI patients, and 10.64 +/- 2.20%/h vs 10.84 +/- 2.26%/h ( P = .848),
respectively, for 7 MVD-MPI patients. The WOR values for normal MPI versus MVD
MPI patients for CZT SPECT were 13.42 +/- 1.53%/h vs 10.64 +/- 2.20%/h ( P =
.025), respectively. Thallium-201-chloride WOR values obtained with high
efficiency CZT SPECT, which enabled significantly reduced imaging times and use
of a low-dose protocol, were similar to those obtained with conventional SPECT.
PMID- 29952218
TI - Cell-surface phenotyping identifies CD36 and CD97 as novel markers of fibroblast
quiescence in lung fibrosis.
AB - Fibroblasts play an important role in lung homeostasis and disease. In lung
fibrosis, fibroblasts adopt a proliferative and migratory phenotype, with
increased expression of alpha-smooth muscle actin (alphaSMA) and enhanced
secretion of extracellular matrix components. Comprehensive profiling of
fibroblast heterogeneity is limited, due to a lack of specific cell-surface
markers. We have previously profiled the surface proteome of primary human lung
fibroblasts. Here, we sought to define and quantify a panel of cluster of
differentiation markers in primary human lung fibroblasts and IPF lung tissue,
using immunofluorescence and FACS analysis. Fibroblast function was assessed by
analysis of replicative senescence. We observed presence of distinct fibroblast
phenotypes in vivo, characterized by various combinations of Desmin, alphaSMA,
CD36, or CD97 expression. Most markers demonstrated stable expression over
passages in vitro, but significant changes were observed for CD36, CD54, CD82,
CD106, and CD140a. Replicative senescence of fibroblasts was observed from
passage 10 onward. CD36- and CD97-positive, but alphaSMA-negative, cells were
present in remodeled areas of IPF lungs. Transforming growth factor-beta
treatment induced alphaSMA and collagen I expression, but repressed CD36- and
CD97 expression. We identified a panel of stable surface markers in human lung
fibroblasts, applicable for positive cell isolation directly from lung tissue.
TGF-beta exposure represses CD36- and CD97 expression, while increasing alphaSMA
expression; we therefore identified complex surface protein changes during
fibroblast-myofibroblast activation. Co-existence of quiescence and activated
fibroblast subtypes in the IPF lung suggests dynamic remodeling of fibroblast
activation upon subtle changes to growth factor exposure in local
microenvironmental niches.
PMID- 29952219
TI - Inhibition of lncRNA PFRL prevents pulmonary fibrosis by disrupting the miR
26a/smad2 loop.
AB - Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease
with increasing mortality and poor prognosis. The current understanding of the
role of long noncoding RNAs (lncRNAs) in IPF remains limited. In the present
study, we identified a lncRNA NONMMUT022554, designated pulmonary fibrosis
regulatory lncRNA (PFRL), with unknown functions and found that its levels were
increased in fibrotic lung tissues of mice and pulmonary fibroblasts exposed to
transforming growth factor (TGF)-beta1. Furthermore, we found that enforced
expression of PFRL induced fibroblast activation and collagen deposition, which
could be mitigated by the overexpression of microRNA (miR)-26a. By contrast, the
inhibition of PFRL could markedly alleviate the TGF-beta1-induced upregulation of
fibrotic markers and attenuate fibroblast proliferation and differentiation by
regulating miR-26a. Meanwhile, our study confirmed that PFRL inhibited the
expression and activity of miR-26a, which has been identified as an antifibrotic
miRNA in our previous study. Interestingly, our molecular study further confirmed
that Smad2 transcriptionally inhibits the expression of miR-26a and that the miR
26a/Smad2 feedback loop mediates the profibrotic effects of PFRL in lung
fibrosis. More importantly, knockdown of PFRL ablated bleomycin-induced pulmonary
fibrosis in vivo. Taken together, our findings indicate that lncRNA PFRL
contributes to the progression of lung fibrosis by modulating the reciprocal
repression between miR-26a and Smad2 and that this lncRNA may be a therapeutic
target for IPF.
PMID- 29952222
TI - Evolution of ARDS biomarkers: Will metabolomics be the answer?
AB - To date, there is no clinically agreed-upon diagnostic test for acute respiratory
distress syndrome (ARDS): the condition is still diagnosed on the basis of a
constellation of clinical findings, laboratory tests, and radiological images.
Development of ARDS biomarkers has been in a state of continuous flux during the
past four decades. To address ARDS heterogeneity, several studies have recently
focused on subphenotyping the disease on the basis of observable clinical
characteristics and associated blood biomarkers. However, the strong correlation
between identified biomarkers and ARDS subphenotypes has yet to establish
etiology; hence, there is a need for the adoption of other methodologies for
studying ARDS. In this review, we will shed light on ARDS metabolomics research
in the literature and discuss advances and major obstacles encountered in ARDS
metabolomics research. Generally, the ARDS metabolomics studies focused on
identification of differentiating metabolites for diagnosing ARDS, but they were
performed to different standards in terms of sample size, selection of control
cohort, type of specimens collected, and measuring technique utilized. Virtually
none of these studies have been properly validated to identify true metabolomics
biomarkers of ARDS. Though in their infancy, metabolomics studies exhibit promise
to unfold the biological processes underlying ARDS and, in our opinion, have
great potential for pushing forward our present understanding of ARDS.
PMID- 29952221
TI - Iloprost attenuates hyperoxia-mediated impairment of lung development in newborn
mice.
AB - Cyclooxygenase-2 (COX-2/PTGS2) mediates hyperoxia-induced impairment of lung
development in newborn animals and is increased in the lungs of human infants
with bronchopulmonary dysplasia (BPD). COX-2 catalyzes the production of
cytoprotective prostaglandins, such as prostacyclin (PGI2), as well as
proinflammatory mediators, such as thromboxane A2. Our objective was to determine
whether iloprost, a synthetic analog of PGI2, would attenuate hyperoxia effects
in the newborn mouse lung. To test this hypothesis, newborn C57BL/6 mice along
with their dams were exposed to normoxia (21% O2) or hyperoxia (85% O2) from 4 to
14 days of age in combination with daily intraperitoneal injections of either
iloprost 200 ug.kg-1.day-1, nimesulide (selective COX-2 antagonist) 100 mg.kg
1.day-1, or vehicle. Alveolar development was estimated by radial alveolar counts
and mean linear intercepts. Lung function was determined on a flexiVent, and
multiple cytokines and myeloperoxidase (MPO) were quantitated in lung
homogenates. Lung vascular and microvascular morphometry was performed, and right
ventricle/left ventricle ratios were determined. We determined that iloprost (but
not nimesulide) administration attenuated hyperoxia-induced inhibition of
alveolar development and microvascular density in newborn mice. Iloprost and
nimesulide both attenuated hyperoxia-induced, increased lung resistance but did
not improve lung compliance that was reduced by hyperoxia. Iloprost and
nimesulide reduced hyperoxia-induced increases in MPO and some cytokines (IL
1beta and TNF-alpha) but not others (IL-6 and KC/Gro). There were no changes in
pulmonary arterial wall thickness or right ventricle/left ventricle ratios. We
conclude that iloprost improves lung development and reduces lung inflammation in
a newborn mouse model of BPD.
PMID- 29952223
TI - Qualitative Methods Used to Generate Questionnaire Items: A Systematic Review.
AB - A systematic review of articles using qualitative methods to generate
questionnaire items identified in MEDLINE and PsycINFO from 2000 to 2014 was
carried out. Articles were analyzed for (a) year of publication and journal
domain, (b) qualitative data collection methods, (c) method of data content
analysis, (d) professional experts' input in item generation, and (e) debriefing
of the newly developed items. In total, 371 articles were included and results
showed (a) an acceleration of published articles, (b) individual interviews and
focus groups were common ways of generating items and no emergent approach was
identified, (c) the content analysis was usually not described (43% of articles),
(d) experts were involved in eliciting concepts in less than a third of articles,
(e) 61% of articles involved a step of further submission of newly developed
items to the population of interest. This review showed an insufficient reporting
of qualitative methods used to generate new questionnaires despite previous
recommendations.
PMID- 29952224
TI - #Hookahlife: The Rise of Waterpipe Promotion on Instagram.
AB - INTRODUCTION: Hookah smoking is becoming increasingly popular worldwide,
especially among young adults. The growth of social media has also enabled
sharing of opinions, experiences, and marketing related to hookah via user
generated content. AIM: To evaluate the portrayal and promotion of hookah on
Instagram and to highlight public health challenges created by this content.
METHOD: A qualitative content analysis was performed on a sample of 301 Instagram
posts made with the hashtags #hookah or #shisha in October 2016. RESULTS: Of the
301 coded posts, 279 were relevant to hookah. These posts were most commonly made
by hookah lounges/bars (29.2%) and individual users (27.6%). Posters were most
commonly from Russia (38.5%), the United States (18.6%), and Germany (10.7%). A
total of 63.8% of the posts were promotional in nature; 19.7% of posts contained
hashtags that expressed hookah identity or community (e.g., #hookahlife); 35.5%
of posts associated nightlife activities with hookah smoking and 33.0% portrayed
hookah smoking as a social activity. Only one post (0.4%) mentioned that hookah
might have negative health effects. Likes were more common on posts depicting
novel rather than traditional hookah designs ( p = .027). CONCLUSIONS: Images
from Instagram may help in understanding health behaviors such as hookah smoking.
Our results suggest that domestic and international hookah promotion is common on
Instagram. Instagram posts cast hookah in an overwhelmingly positive light and
may normalize hookah use through associations with nightlife, community, and
hookah identity. Policy makers and researchers should explore approaches for
reducing the volume of promotional posts and tailoring counter-marketing to the
specific themes presented on social media.
PMID- 29952225
TI - Biologic Therapy Utilization in Patients With Moderate to Severe Psoriasis and
Psoriatic Arthritis: An Observational Summary of Biologic Therapy Use in a
Clinical Setting.
AB - Plaque psoriasis affects approximately 2% to 3% of the global population, with
psoriatic arthritis observed in approximately 20% to 30% of these individuals.
Upon advances in research pathophysiology and treatment over the past decade,
biologic therapies have been used more to treat moderate to severe psoriasis. In
Canada, reimbursement bodies have defined prior authorization criteria to
determine patient eligibility for funding of biologic treatments in moderate to
severe plaque psoriasis. Generally, patients will have been treated with
conventional therapies such as topical steroids, phototherapy, or systemic
treatments such as methotrexate and cyclosporine before starting a biologic
therapy. In difficult cases or severe flares in otherwise controlled disease,
practitioners may augment the regimen with one or more conventional treatments.
The objective of this observational report was to identify treatment pathways for
psoriasis and psoriatic arthritis patients in Canada by examining initial
biologic treatment and subsequent treatment optimization patterns for informed
reimbursement discussions and decisions. A retrospective chart review was
conducted at Newlab Clinical Research using medical records of patients who
received at least 1 of 4 biologic agents approved at that time of the survey in
Canada for the treatment of plaque psoriasis (adalimumab, etanercept, infliximab,
ustekinumab). The study population consisted of patients who had moderate to
severe plaque psoriasis, diagnosed by a dermatologist, for at least 6 months
before the study index date and who attended Newlab Clinical Research between
2008 and 2013. All current and previous agents prescribed for the treatment of
psoriasis were captured. A total of 248 patients with psoriasis treated with
biologics were identified, of whom 27 (10.9%) were also diagnosed with psoriatic
arthritis. Prior to initiating treatment with a biologic, most patients (72.1%)
were treated with (or contraindicated to) methotrexate/cyclosporine. Treatment
was supplemented with topical agents (70.6%) and/or followed by a course of
ultraviolet light phototherapy (51.6%). Only 2.4% of patients were treated with a
biologic first. Of 248 patients treated with biologics, almost half (47.6%)
needed add-on therapy, whereas 16.5% of patients had an increase in dose or
dosing interval. Furthermore, 14.1% of patients added a topical agent, 10.5% a
topical steroid, or 6.5% a course of phototherapy while continuing biologic
therapies. Finally, 30.4% of patients switched to another biologic treatment.
Adalimumab was the most common agent used as a second-line agent (37.2%), and
patients who started on adalimumab mainly switched to ustekinumab as a second
line agent (73.9%). Infliximab was the agent least often used as second-line
therapy.
PMID- 29952220
TI - Mechanisms of organophosphorus pesticide toxicity in the context of airway
hyperreactivity and asthma.
AB - Numerous epidemiologic studies have identified an association between
occupational exposures to organophosphorus pesticides (OPs) and asthma or
asthmatic symptoms in adults. Emerging epidemiologic data suggest that
environmentally relevant levels of OPs may also be linked to respiratory
dysfunction in the general population and that in utero and/or early life
exposures to environmental OPs may increase risk for childhood asthma. In support
of a causal link between OPs and asthma, experimental evidence demonstrates that
occupationally and environmentally relevant OP exposures induce bronchospasm and
airway hyperreactivity in preclinical models. Mechanistic studies have identified
blockade of autoinhibitory M2 muscarinic receptors on parasympathetic nerves that
innervate airway smooth muscle as one mechanism by which OPs induce airway
hyperreactivity, but significant questions remain regarding the mechanism(s) by
which OPs cause neuronal M2 receptor dysfunction and, more generally, how OPs
cause persistent asthma, especially after developmental exposures. The goals of
this review are to 1) summarize current understanding of OPs in asthma; 2)
discuss mechanisms of OP neurotoxicity and immunotoxicity that warrant
consideration in the context of OP-induced airway hyperreactivity and asthma,
specifically, inflammatory responses, oxidative stress, neural plasticity, and
neurogenic inflammation; and 3) identify critical data gaps that need to be
addressed in order to better protect adults and children against the harmful
respiratory effects of low-level OP exposures.
PMID- 29952230
TI - The Compelling and Persistent Problem of Bipolar Disorder Disguised as Major
Depression Disorder: An Integrative Review [Formula: see text].
AB - BACKGROUND: Up to 40% of patients with bipolar disorder are misdiagnosed, usually
with major depression disorder. OBJECTIVE: The purpose was to describe the
current state of the science of the misdiagnosis of bipolar disorder, with the
ultimate goal of improving psychiatric diagnostic workups including screening.
DESIGN: An integrative review was conducted using standard criteria for
evaluating research articles. RESULTS: Forty-nine articles met the eligibility
criteria. Articles explored patient-related and health care provider-related
factors contributing to the misdiagnosis of bipolar disorder as well as
consequences of misdiagnosis. Clinically oriented, reliable, and valid screening
tools for bipolar disorder also were reviewed. CONCLUSIONS: Awareness of
multiple, challenging patient-related factors and more comprehensive assessment
and screening by health care providers may reduce misdiagnosis.
PMID- 29952231
TI - Improving selectivity and sensitivity of protein quantitation by LC-HR-MS/MS:
determination of somatropin in rat plasma.
AB - AIM: Protein quantitation by digestion of a biological sample followed by LC-MS
analysis of a signature peptide can be a challenge because of the high complexity
of the digested matrix. Results/methodology: The use of LC with high-resolution
(quadrupole-TOF) MS detection allowed quantitation of the 22-kDa
biopharmaceutical somatropin in 60 MUl of rat plasma down to 25 ng/ml with
minimal further sample treatment. Reducing the mass extraction window to 0.01 Da
considerably decreased the interference of tryptic peptides, enhanced sensitivity
and improved accuracy and precision. Analysis with LC-MS/MS resulted in a less
favorable limit of quantitation of 100 ng/ml. CONCLUSION: HRMS is an interesting
option for the quantitation of proteins after digestion and has the potential to
improve sensitivity with minimal method development.
PMID- 29952232
TI - When People Co-occur With Good or Bad Events: Graded Effects of Relational
Qualifiers on Evaluative Conditioning.
AB - Studies on evaluative conditioning show that a change in liking can occur
whenever stimuli are paired. Such instances of attitude change are known to
depend on the type of relation established between stimuli (e.g., "Bob is a
friend of Mike" vs. "Bob is an enemy of Mike"). Research has so far only compared
assimilative and contrastive relational qualifiers (e.g., friend vs. enemy). For
the first time, we compared the effect of nonoppositional qualifiers on attitude
change in an evaluative conditioning procedure (e.g., "Bob causes Positive
Outcomes" vs. "Bob predicts Positive Outcomes"). Differential effects of
nonoppositional relational qualifiers were observed on explicit and implicit
evaluations. We discuss the implications of our findings for attitude research,
theories of attitude change, and optimizing evaluative conditioning for changing
attitudes in applied settings.
PMID- 29952233
TI - Mindfulness and human occupation: A scoping review.
AB - BACKGROUND: Mindfulness is an emergent construct with implications for our
understanding of approaches to engagement in human occupation. Little is known
about how mindfulness is being applied and what its possibilities are in the
occupation-based disciplines. OBJECTIVE: The purpose of this scoping review was
to summarize, describe, and identify gaps in the existing literature on
mindfulness in relation to human occupation. MATERIAL AND METHOD: A scoping
review, guided by Arksey and O'Malley's methodological framework was undertaken.
The initial search yielded 929 articles; 20 articles met the criteria for
inclusion. Articles included peer review and gray literature published in English
between 2006-2016. Articles addressed mindfulness in OT or OS and included the
terms 'human occupation', 'occupational therapy' and/or 'occupational therapist',
and 'mindfulness' and/or 'meditation' or 'yoga'. FINDINGS: The qualitative
thematic analysis identified an overarching theme of mindful occupation, with 5
sub-themes including occupational presence; occupational awareness; occupational
engagement; occupational well-being; and occupational fulfillment. CONCLUSIONS
AND SIGNIFICANCE: The findings have important implications for practice,
education, theory and research. Future directions should focus on more depth and
breadth of empirical research about mindful engagement in human occupation that
can be used to implement and evaluate mindfulness in occupation-based theory and
practice.
PMID- 29952234
TI - Experiences of general practitioners participating in oncology meetings with
specialists to support GP-led survivorship care; an interview study from the
Netherlands.
AB - BACKGROUND: Due to ageing, increasing cancer incidence and improved treatment,
the number of survivors of cancer increases. To overcome the growing demand for
hospital care survivorship by the involvement of the general practitioner (GP)
has been suggested. Dutch GPs started a project to offer survivorship care to
their patients with the help of monthly oncology meetings with hospital
specialists. OBJECTIVES: To evaluate the experiences of GPs with monthly oncology
meetings in a GP-practice to support GP-led survivorship care of colon cancer
patients. METHODS: This is a qualitative study in primary care centres in a
region in the Netherlands around one hospital. GPs were recruited from practices
organizing monthly oncology meetings with hospital specialists. Ten of 15
participating GPs were interviewed until saturation. The interviews were
transcribed verbatim and two independent researchers analysed the data. RESULTS:
The oncology meetings and individual care plans attributed to a feeling of shared
responsibility for the patients by the GP and the specialist. The meetings helped
the GPs to be informed about the patients in the diagnostic and treatment phase,
which was followed by a clear moment of transfer from hospital to primary care.
GPs were better equipped to treat comorbidity and were more confident in
providing survivorship care. Due to lack of reimbursement for survivorship care,
the internal motivation of the GP must high. CONCLUSION: The oncology meetings
fulfil the need for information and communication. Close cooperation between GPs
and oncology specialists appears to be an essential factor for GPs to value GP
led survivorship care positively.
PMID- 29952235
TI - A Randomized Feasibility Trial to Evaluate Use of the Jaw Dynasplint to Prevent
Trismus in Patients With Head and Neck Cancer Receiving Primary or Adjuvant
Radiation-Based Therapy.
AB - OBJECTIVE: This study was designed to assess the feasibility of using the Jaw
Dynasplint System as an adjunct to conventional stretching exercises as a
preventative measure against trismus in patients undergoing radiotherapy.
METHODS: Study participants (n = 40) were randomized using a permuted block
design to conventional stretching or stretching plus use of the Jaw Dynasplint 3
times per day for 30 minutes. Patients were instructed to record maximum
interincisal opening each day as well as logging use of the Jaw Dynasplint.
RESULTS: At 6 months after initiation of the preventative regimen, 50% of
patients in the Dynasplint arm and 75% in the conventional stretching arm
remained on their assigned therapy. Trismus was diagnosed in 2 patients in the
control arm and in 4 patients in the Dynasplint arm. Only 25% (95% confidence
interval = 11.1, 46.9) of patients in the Dynasplint arm used the device as
prescribed. CONCLUSIONS: The addition of the Jaw Dynasplint decreased compliance
compared with conventional stretching. It is unlikely that the prescribed regimen
will prove efficacious as a preventative measure due to low compliance.
PMID- 29952236
TI - Impact of psychological profile on drug adherence and drug resistance in patients
with apparently treatment-resistant hypertension.
AB - PURPOSE: Patients with apparent treatment-resistant hypertension (a-TRH) are
often poorly adherent to drug treatment and have an unusual personal history and
psychological profile. The aim of this study was to identify predictors of drug
adherence and drug resistance in a cohort of patients with aTRH, with emphasis on
psychological characteristics. METHODS: All patients with confirmed aTRH on
standardized antihypertensive treatment were eligible. Drug adherence was
assessed by drug dosages in urine using Liquid Chromatography coupled with tandem
Mass Spectrometry (LC-MS/MS). Drug resistance was assessed by 24-hour ambulatory
blood pressure adjusted for the number of antihypertensive drugs and for drug
adherence. Psychological profile was assessed using a broad array of validated
questionnaires. RESULTS: The analysis included 35 consecutive patients. The
proportion of adherent, partly adherent and totally non-adherent patients was 29,
40 and 31%, respectively. In regression analysis, independent predictors of poor
drug adherence were recent hospital admission for hypertension, a lower ability
to put things into perspective when facing negative events and a higher tendency
to somatize, accounting for 51% of variability in drug adherence. Independent
predictors of treatment resistance were a higher recourse to the strategies of
blaming others and oneself, accounting for 37% of variability in drug treatment
resistance. CONCLUSION: In patients with aTRH, poor adherence is frequent but
does not entirely account for treatment resistance. Psychological characteristics
appear as strong predictors of both drug adherence and drug resistance. Our
results suggest that therapeutic drug monitoring and psychological evaluation
should be an integral part of assessment of patients with aTRH.
PMID- 29952237
TI - Top-down LC-MS quantitation of intact denatured and native monoclonal antibodies
in biological samples.
AB - AIM: The requirements for developing antibody biotherapeutics benefit from
understanding the nature and relevant aspects of the entire molecule. The method
presented herein employs on-line multidimensional LC-quadrupole time-of-flight
(QTOF)-MS for the quantitative determination of an antibody isolated from
biological samples while maintaining the intact native biologically active
conformation of the antibody. RESULTS: Following method optimization for a model
antibody, an incurred biotherapeutic in cynomologus monkey was quantified in its
intact top-down native conformation. A partial method validation demonstrated
acceptable precision and accuracy although improved sensitivity requires further
studies. CONCLUSION: An on-line multidimensional LC-MS approach presents a proof
of-principle example for quantifying an intact, native antibody isolated from an
incurred biological sample via immunoaffinity techniques coupled with top-down
QTOF LC-MS bioanalysis.
PMID- 29952238
TI - How the West can help to develop mental health services in resource-limited
settings.
PMID- 29952239
TI - Barriers to Health Care Services Among Palestinian Women Denied Family
Unification in Israel.
AB - Family unification received public and political attention following recent
global immigration crises, though less within health research. In Israel, under
the Family Reunification Order, about 20,000 Palestinian women from the Occupied
Palestinian Territories are denied residency and the right to universal health
care services (HSC) after marrying Palestinian citizens and moving to Israel. To
better understand the relationship between lacking residency and barriers to
accessing HCS, we conducted in-depth interviews with 21 Palestinian women (ages
22-59) denied family unification. Our findings revealed that in addition to
hindering access to HCS, lacking residency intersects with other political,
social, and economic determinants of these women's health and disrupts normal
family life. Lacking residency intensifies poverty (via private health insurance
and legal fees, permit extensions) and leads to family separations and risky
crossings at military checkpoints into the West Bank for medical treatment.
Restrictions on freedom of movement engender fear of deportation and precarity.
Denial of residency also exacerbates gender inequality (increased dependence on
husbands) and can endanger child custody when mothers' lack of residency passes
to children, violating children's basic rights. Allowing family unification to
Palestinian women would remove barriers to HCS access, allow normal family life,
and permit social integration.
PMID- 29952240
TI - Accurate differentiation of novel Staphylococcus argenteus from Staphylococcus
aureus using MALDI-TOF MS.
AB - AIM: We evaluated a Staphylococcus argenteus-specific diagnostic profile of
matrix-assisted laser desorption/ionization time-of-flight mass spectrometer for
accurate identification of this novel bacterium. MATERIALS & METHODS:
Staphylococcus argenteus was identified based on negative crtM gene and presence
of specific sequence types. A classification model was generated by cluster
analysis of matrix-assisted laser desorption/ionization time-of-flight mass
spectrometer results and ClinProTools software for 25 S. argenteus and 25
methicillin-susceptible S. aureus (MSSA). The performance of the classification
model was validated against 72 S. argenteus and 72 MSSA isolates. RESULTS: With
cluster analysis and classification model, differentiation of 72 S. argenteus
from 72 MSSA had 100.0% accuracy by chemical extraction method and 87.5%
sensitivity and 100.0% specificity by direct smear method. CONCLUSION: The
classification model could accurately differentiate S. argenteus from MSSA.
PMID- 29952242
TI - From Snapshots to Movies: The Association Between Retirement Sequences and Aging
Trajectories in Limitations to Perform Activities of Daily Living.
AB - OBJECTIVE: This study analyzes the dynamic association between retirement
sequences and activities of daily living (ADLs) trajectories between ages 60 and
70. METHOD: Retirement sequences previously established for 7,880 older Americans
from the Health and Retirement Study were used in hierarchical linear and
propensity score full matching models, analyzing their association with ADL
trajectories. RESULTS: Sequences of partial retirement from full- or part-time
jobs showed higher baseline and slower decline in ADL than sequences
characterized by early labor force disengagement. DISCUSSION: The conventional
model in which people completely retire from a full-time job at normative ages
and the widely promoted new conventional model of late retirement are both
associated with better functioning than early labor force disengagement. But
unconventional models, where older adults keep partially engaged with the labor
force are also significantly associated with better functioning. These findings
call attention to more research on potential avenues to simultaneously promote
productive engagement and health later in life.
PMID- 29952241
TI - Whole Body Vibration Exposure on Markers of Bone Turnover, Body Composition, and
Physical Functioning in Breast Cancer Patients Receiving Aromatase Inhibitor
Therapy: A Randomized Controlled Trial.
AB - INTRODUCTION: Women with breast cancer are often prescribed aromatase inhibitors,
which can cause rapid loss of bone mass leading to significant potential for
morbidity. Vibration training has been shown to be helpful in reducing bone
turnover in postmenopausal women without cancer. AIM: To examine the effect of
vibration stimulus on markers of bone turnover in breast cancer patients
receiving aromatase inhibitors. METHODS: Thirty-one breast cancer survivors
undergoing treatment with aromatase inhibitors were randomized to vibration
stimulus (n = 14) or usual care control (n = 17). Low-frequency and low-magnitude
vibration stimulus (27-32 Hz, 0.3 g) was delivered in supervised sessions via
standing on a vibration platform for 20 minutes, 3 times per week for 12 weeks.
The primary outcome was blood markers of bone resorption (serum N-telopeptide
X/creatine) and formation (serum type 1 procollagen N-terminal propeptide; P1NP).
Other study outcomes body composition as well as measures of physical
functioning. Outcomes were compared between groups using analysis of covariance
adjusted for baseline values as well as time on aromatase inhibitors. OUTCOMES:
On average, participants were 61.5 years old and overweight (ie, body mass index
= 28.5 kg/m2). Following vibration training, there was no significant difference
between groups for bone resorption (adjusted group difference 0.5, P = .929) or
formation (adjusted group difference 5.3, P = .286). There were also no changes
in any measure of physical functioning body composition. CONCLUSIONS: Short-term
low-magnitude vibration stimulus does not appear to be useful for reducing
markers of bone turnover secondary to aromatase inhibitors in breast cancer
patients; nor is it useful in improving physical function or symptoms. However,
further investigations with larger samples and higher doses of vibration are
warranted. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials
Registry (ACTRN12611001094965).
PMID- 29952243
TI - E-recruitment into a bipolar disorder trial using Facebook tailored advertising.
PMID- 29952244
TI - Who Cares? Effects of Social Approach and Avoidance Motivation on Responsiveness
to Others.
AB - Responsiveness to others (i.e., our understanding, validation, and support of
important aspects of others) significantly contributes to positive social
relationships. In the present research, we found evidence that responsiveness has
motivational origins. In two experiments, participants who were approaching
positive social outcomes had a higher level of responsiveness compared with
participants who were avoiding negative social outcomes. A third experiment
disentangled the roles of motivation and situation valence. Positive (compared
with negative) social situations were associated with higher approach motivation,
lower avoidance motivation, and a higher level of responsiveness. However, within
a given situation, both approach and avoidance motivation were associated with a
higher level of responsiveness. This association was even stronger in negative
situations, suggesting that both approach and avoidance motivation might be ways
of behaving responsively in potentially difficult social situations. The effects
were independent of relationship closeness and partly weaker in older compared
with younger adults.
PMID- 29952245
TI - Exploring Racial Differences Surrounding Prostate Cancer Screening: Beliefs and
Attitudes in Community Dwelling Men Attending an Urban Men's Health Event.
AB - The purpose of the study was to explore attitudes/beliefs in men attending an
urban health fair to explore barriers to prostate cancer (PCa) screening. Five
hundred and forty-four men attending the PCa booth at the fair in 2014 or 2015
completed questionnaires about PCa. Data were examined using Pearson's chi2,
Fisher's Exact, and Wilcoxon rank tests after grouping men by African American
(AA) and non-African American ethnicity. Three hundred and twenty-six (60%) men
were AA and two hundred and eighteen (40%) were non-AA (89% white). Median age
(54 vs. 56 years) and prior PCa screening were similar between AA and non-AA;
income ( p = .044) and education ( p = .0002) differed. AA men were less likely
to have researched prostate-specific antigen (PSA) on the internet ( p = .003),
but more used TV ( p = .003) and media ( p = .0014) as information sources.
Family members had a stronger influence over screening decisions for AA men ( p =
.005). After reading PSA information, AA men were more likely to still be
confused ( p = .008). A higher proportion of AA men were less worried about dying
from PCa ( p = .0006), but would want treatment immediately instead of watchful
waiting ( p < .0001). Interestingly, a higher proportion of AA men indicated that
they would prefer not to know if they had PCa ( p = .001). Ultimately, more AA
men had a PSA done (98.4% vs. 95.1%; p = .031). When considering screening
eligible men, a higher proportion of AA men had an abnormal PSA (13.1% vs. 5.3%;
p = .037). AA men's beliefs surrounding PCa differ from non-AA men, and should be
considered when developing culturally appropriate education, screening, and
treatment strategies for this group.
PMID- 29952246
TI - Role of Angptl4/Fiaf in exercise-induced skeletal muscle AMPK activation.
AB - Angiopoietin-like protein 4 (Angptl4)/fasting-induced adipose factor (Fiaf)
expression levels are increased by exercise in skeletal muscle. We have
previously shown that Angptl4 regulates food intake and energy expenditure via
modulation of hypothalamic AMP-activated protein kinase (AMPK) activity. AMPK is
an important signaling molecule that integrates skeletal muscle metabolism during
exercise. Therefore, we investigated the involvement of Angptl4 in exercise
induced AMPK activation in skeletal muscle. Angptl4 protein and mRNA expression
levels were significantly increased in the gastrocnemius and soleus muscles of
mice following a 50-min running bout. Treatment of C2C12 myotubes with Angptl4
increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), which were
markers of AMPK activation, and the mitochondrial maximum respiratory capacity.
Treadmill exercise increased AMPK and ACC phosphorylation in the gastrocnemius of
normal mice; this phosphorylation increase was attenuated in mice lacking
Angptl4. Endurance to swimming and hanging was also reduced in Angptl4 knockout
mice. Taken together, our current data demonstrate that exercise-induced
upregulation of skeletal muscle Angptl4 is critical for AMPK activation and
exercise tolerance. These findings unveil a new role for skeletal muscle Angptl4
in exercise physiology. NEW & NOTEWORTHY 1) Angiopoietin-like protein 4 (Angptl4)
treatment activates AMP-activated protein kinase (AMPK) signaling in skeletal
muscle cells. 2) Angptl4 increases the maximum mitochondrial oxidative capacity
through AMPK activation in skeletal muscle cells. 3) Lack of Angptl4 mitigates
exercise-induced skeletal muscle AMPK activation. 4) Angptl4-deficient mice show
a lower endurance to exercise.
PMID- 29952247
TI - Cardiac autonomic and left ventricular mechanics following high intensity
interval training: a randomized crossover controlled study.
AB - Physical inactivity and sedentary behavior is associated with increased
cardiovascular disease risk. Short duration high-intensity interval training
(HIIT) has been shown to improve important health parameters. The aim of the
present study was to assess the combined adaptations of the cardiac autonomic
nervous system and myocardial functional and mechanical parameters to HIIT. Forty
physically inactive and highly sedentary men completed two weeks of HIIT and
control period. The HIIT protocol consisted of 3 * 30-s maximal cycle ergometer
sprints against a resistance of 7.5% body weight, interspersed with 2 min of
active recovery. Total power spectral density (PSD) and associated low-frequency
(LF) and high-frequency (HF) power spectral components of heart rate variability
were recorded. Conventional and speckle tracking echocardiography recorded left
ventricular (LV) structural, functional, and mechanical parameters. HIIT produced
a significant increase in total log-transformed (ln) PSD and ln HF and a
significant decrease in LF/HF ratio (all P < 0.05) compared with the control
period. HIIT produced significant improvements in LV diastolic function,
including lateral E', estimated filling pressure (E/E' ratio), E deceleration
time, and isovolumetric relaxation time ( P < 0.05 for all). Fractional
shortening was the only conventional marker of LV systolic function to
significantly improve ( P < 0.05). In this setting, there were significant
improvements in global peak systolic strain rate, early and late diastolic strain
rate, and early to late diastolic strain rate ratio, as well as apical rotation,
apical systolic and diastolic rotation velocity, apical radial and
circumferential strain and strain rate, LV torsion, and LV systolic and diastolic
torsion velocity (all P < 0.05). A short-term program of HIIT was associated with
a significant increase in cardiac autonomic modulation, demonstrated by a
residual increase in cardiac vagal activity as well as significantly improved
cardiac function and mechanics. This study demonstrates that HIIT may be an
important stimulus to reduce the health implications associated with physical
inactivity and sedentary behavior. NEW & NOTEWORTHY This is the first study to
measure the combined adaptations of the cardiac autonomic nervous system and
myocardial function and mechanics following high-intensity interval training
(HIIT). This study demonstrates that a 2-wk HIIT intervention provides
significant improvements in cardiac autonomic modulation and myocardial function
and mechanics in a large cohort of young physically inactive and highly sedentary
individuals. HIIT may be a powerful stimulus to reduce the health implications
associated with physical inactivity and sedentary behavior.
PMID- 29952248
TI - Are the Elderly Perceived as a Burden to Society? The Perspective of Family
Caregivers in Belgium and Kenya: A Comparative Study.
AB - INTRODUCTION: It is estimated that 70% to 80% of informal care for frail and
disabled elders is provided by family caregivers (FCGs). AIM: To better
understand how caregiving for the elderly has affected FCGs lives and to compare
the perspective of these caregivers in Belgium and Kenya. METHOD: Semistructured
interviews were undertaken with 15 FCGs in Kenya and 15 FCGs in Belgium.
Interpretative phenomenological analysis was used to identify themes. RESULTS:
Themes discovered in the experience of family caregiving included profile of the
care receiver, impact of caregiving on the FCG, cultural values and norms,
challenges in caregiving, coping strategies and caregiver well-being. DISCUSSION:
FCGs in both Kenya and Belgium identified experiencing serious concerns. In
Kenya, the lack of resources and formal structures play a more important role
than in Belgium. Despite this difference, culture-specific views and norms are
paramount to explaining the FCG experience in the two countries.
PMID- 29952249
TI - Expression of selected epithelial-mesenchymal transition transcription factors in
serous borderline ovarian tumors and type I ovarian cancers.
AB - Epithelial ovarian neoplasms are a heterogeneous group including tumor subsets
with distinct clinicopathologic and molecular features. Recent evidence from
molecular and genomic studies suggests that whereas low-grade serous carcinomas
and high-grade serous carcinomas likely develop on two separate pathways, the low
grade serous carcinomas and serous borderline ovarian tumors may represent
various stages of the same developmental continuum. The transformation of
borderline ovarian tumors into an invasive neoplasm is associated with an array
of molecular changes, inter alia controlled by p53 and PI3K/Akt pathway, as well
as with a decrease in E-cadherin expression. The latter implies that epithelial
mesenchymal transition is a critical determinant of borderline ovarian tumor
invasiveness. The aim of this study was to analyze the expression of
transcription factors involved in epithelial-mesenchymal transition: SNAIL, SLUG,
TWIST 1, TWIST 2, ZEB 1, and ZEB 2 in borderline tumors and type I ovarian
cancers. The study included tissue specimens from 42 patients with
histopathologically verified ovarian masses. The expressions for SLUG, TWIST 1,
ZEB1, and ZEB 2 were scored based on the nuclear staining, and the expressions of
SNAIL and TWIST 2 based on the cytoplasmic and/or nuclear staining. The
proportions of ovarian tumors with the immunoexpression of the epithelial
mesenchymal transition transcription factors were 85.7% for SNAIL, 100% for SLUG,
9.5% for TWIST 1, 95.2% for TWIST 2, 23.8% for ZEB 1, and 0% for ZEB 2. The
expression patterns of SNAIL, SLUG, TWIST, and ZEB identified in this study
suggest that both serous borderline ovarian tumors and type I ovarian cancers
undergo dynamic epithelial-mesenchymal interconversions. Our findings obtained in
the two groups of tumors which shared some etiopathogenic pathways imply that the
expression of the epithelial-mesenchymal transition transcription factors may be
activated at early stages of the epithelial-mesenchymal transition, and thus
these molecules may play a pivotal role in the development of both serous
borderline ovarian tumors and type I ovarian cancer.
PMID- 29952250
TI - Body dysmorphic disorder: a guide to identification and management for the
orthodontic team.
AB - Body dysmorphic disorder (BDD) is a psychiatric disorder in which the individual
has a disproportionate concern about a particular body part. With the increasing
demand for aesthetic treatments, it is likely that individuals with BDD may
present for orthodontic or combined orthodontic and orthognathic treatment. In
this review, we shall outline the features of BDD and its prevalence, before
discussing the best way for clinicians to identify and manage individuals with
this disorder.
PMID- 29952253
TI - Immunoglobulin G4-related systemic disease with vascular involvement.
PMID- 29952251
TI - Contemporary best practice in the management of malignant pleural effusion.
AB - Malignant pleural effusion (MPE) affects more than 1 million people globally.
There is a dearth of evidence on the therapeutic approach to MPE, and not
surprisingly a high degree of variability in the management thereof. We aimed to
provide practicing clinicians with an overview of the current evidence on the
management of MPE, preferentially focusing on studies that report patient-related
outcomes rather than pleurodesis alone, and to provide guidance on how to
approach individual cases. A pleural intervention for MPE will perforce be
palliative in nature. A therapeutic thoracentesis provides immediate relief for
most. It can be repeated, especially in patients with a slow rate of recurrence
and a short anticipated survival. Definitive interventions, individualized
according the patient's wishes, performance status, prognosis and other
considerations (including the ability of the lung to expand) should be offered to
the remainder of patients. Chemical pleurodesis (achieved via intercostal drain
or pleuroscopy) and indwelling pleural catheter (IPC) have equal impact on
patient-based outcomes, although patients treated with IPC spend less time in
hospital and have less need for repeat pleural drainage interventions. Talc
slurry via IPC is an attractive recently validated option for patients who do not
have a nonexpandable lung.
PMID- 29952252
TI - Stent fractures after common femoral artery bail-out stenting due to suture
device failure in TAVR.
AB - BACKGROUND: Vascular access site-related complications are frequent in the
context of transfemoral transcatheter aortic valve replacement (TAVR). The
implantation of a covered stent graft is an effective treatment option for
bleeding control. However, the external iliac and common femoral arteries are
exposed to flexion of the hip joint. Therefore, stent compression and stent/strut
fractures may occur, facilitating stent occlusion. PATIENTS AND METHODS: In all
389 patients who received transfemoral TAVR from 2013-2015 at the Dusseldorf
Heart Centre, we monitored the management of vascular access site-related
complications. Our analyses focused on immediate technical success and bleeding
control, primary patency, and the occurrence of stent/strut fractures after six
to 12 months of follow-up. RESULTS: Vascular access site-related complications
occurred in 13 % (n = 51), whereof in 10 patients, the bleeding was successfully
managed by prolonged compression. In 40 out of 51 patients, a covered stent graft
was implanted in the common femoral artery, leading to 100 % immediate bleeding
control. After a mean follow-up of 334 +/- 188 days, 28 stents out of 29 patients
with completed follow-up (excluding e. g. death) were without flow-limiting
stenosis (primary patency 97 %) or relevant stent compression (diameter pre/post
8.6/8.1 mm, p = 0.048, late lumen loss 1.1 +/- 0.2 mm, mean flow velocity 92 +/-
34 cm/s). In four asymptomatic patients, stent/strut fractures were detected (14
%) without flow-limiting stenosis. CONCLUSIONS: The implantation of a covered
stent graft is highly effective and safe to control vascular access site-related
complications after TAVR. Stent/strut fractures in the flexible segment of the
common femoral artery may occur, as consequently verified by X-ray visualization,
but show no impairment on flow or clinical parameters after six to 12 months.
PMID- 29952254
TI - Catheter-related venous thrombosis.
PMID- 29952255
TI - Establishing an integrated model of subacute care for the frail elderly.
AB - The current health system in Ontario is not designed to meet the needs of frail
older adults. This is particularly true for older adults hospitalized due to
exacerbation of chronic illness or medical crisis. This article describes the
Subacute Care Unit for the Frail Elderly (SAFE) program, one which is designed to
serve frail older patients who are at risk of deconditioning or disability
associated with prolonged hospitalization but who may safely return home or to a
retirement home following up to 4 weeks of subacute care in a restorative
environment. The program centres on an intense restorative and integrated care
delivery model. The patient population is medically complex, requiring medical
supervision and regular adjustment to the care plan to optimize medical status.
Individuals are no longer acutely ill and are considered stable or stabilizing.
Care and services are designed to improve outcomes for hospitalized frail older
adults by proactively addressing the conditions that contribute to alternate
level of care before the deconditioning associated with prolonged hospitalization
is experienced.
PMID- 29952256
TI - Delivering improved patient and system outcomes for hospitalized older adults
through an Acute Care for Elders Strategy.
AB - Acute care hospitals are widely recognized as potentially high-risk environments
for older adults. In 2010, Mount Sinai Hospital conceived its Acute Care for
Elders (ACE) Strategy as a multi-component intervention to improve the care of
hospitalized older adults. In order to determine its effectiveness, we conducted
a quasi-experimental time series analysis of 12,008 older patients admitted non
electively for acute medical issues over a 6-year period. Despite a 53% increase
in annual admissions of older patients between 2009/2010 and 2014/2015, Mount
Sinai decreased total lengths of stay and readmissions and reduced the direct
cost of care per patient, leading to net savings of CDN$4.2 million in 2014/2015.
This article presents Mount Sinai's ACE Strategy and discusses the benefits of
implementing integrated evidence-based models across the continuum of care and
how it is supporting the implementation of ACE Strategy models of care and care
practices across Canada and beyond.
PMID- 29952257
TI - Using simulation modelling to test the impact of future demand for end-of-life
care.
AB - Health systems globally are exploring new models of care to address the
increasing demand for palliative, hospice, and end-of-life care. Yet few tools
exist at the population level to explore "what if" scenarios and test, in a "cost
avoidance environment," the impact of these new care models on policy, workforce,
technology, and funding. This article introduces the application of scenario
based "what if" thinking and discrete event simulation in strategic planning for
a not-for-profit hospice organization. It will describe how a set of conceptual
models was designed to frame discussions between strategic partners about the
implications and alternatives in implementing a new, integrated service model for
palliative and end-of-life care.
PMID- 29952258
TI - Introduction of the trapezoidal thermodynamic technique method for measuring and
mapping the efficiency of waste-to-energy plants: A potential replacement to the
R1 formula.
AB - Waste-to-energy plants have the peculiarity of being considered both as energy
production and as waste destruction facilities and this distinction is important
for legislative reasons. The efficiency of waste-to-energy plants must be
objective and consistent, independently if the focus is the production of energy,
the destruction of waste or the recovery/upgrade of materials. With the
introduction of polygeneration technologies, like gasification, the production of
energy and the recovery/upgrade of materials, are interconnected. The existing
methodology for assessing the efficiency of waste-to-energy plants is the R1
formula, which does not take into consideration the full spectrum of the
operations that take place in waste-to-energy plants. This study introduces a
novel methodology for assessing the efficiency of waste-to-energy plants and is
defined as the 3T method, which stands for 'trapezoidal thermodynamic technique'.
The 3T method is an integrated approach for assessing the efficiency of waste-to
energy plants, which takes into consideration not only the production of energy
but also the quality of the products. The value that is returned from the 3T
method can be placed in a tertiary diagram and the global efficiency map of waste
to-energy plants can be produced. The application of the 3T method showed that
the waste-to-energy plants with high combined heat and power efficiency and high
recovery of materials are favoured and these outcomes are in accordance with the
cascade principle and with the high cogeneration standards that are set by the EU
Energy Efficiency Directive.
PMID- 29952259
TI - Targeting Glycosylation Aberrations To Improve The Efficiency Of Cancer
Phototherapy.
AB - The use of photodynamic therapy in cancer still remains limited, partly because
of the lack of photosensitizer (PS) specificity for the cancerous tissues.
Various molecular tools are available to increase PS efficiency by targeting the
cancer cell molecular alterations. The most strategies use the protein-protein
interactions, e.g. monoclonal antibodies directed toward tumor antigens, such as
HER2 or EGFR. An alternative could be the targeting of the tumor glycosylation
aberrations, e.g. T/Tn antigens that are truncated O-glycans over-expressed in
numerous tumors. Thus, to achieve an effective targeting, PS can be conjugated to
molecules that specifically recognize the O-glycosylation aberrations at the
cancer cell surface.
PMID- 29952260
TI - Macrophage flipping from foe to friend: A matter of interest in breast carcinoma
heterogeneity driving drug resistance.
AB - Tumor heterogeneity within various cancer types including breast carcinoma is
pivotal in the manifestations of tumor hallmarks. Tumor heterogeneity is seen as
a common landscape where intra-tumoral components including cellular and non
cellular factors create interface with outside environment that lead to the
unique identity of a specific cancer type. Among various contributors to tumor
heterogeneity, cellular heterogeneity immensely plays a role in drug resistance
and relapse of cancer. Within cellular heterogeneity of tumor, tumor-associated
macrophages (TAMs) are pro-tumor type of immune cells that promote growth,
metastasis and drug resistance in breast carcinoma and other cancer types.
Revealing the molecular aspects of TAMs can provide a breakthrough to remove
therapeutics blockade to existing drugs and these understanding in future pave
the way a new class of cancer immunotherapeutic. This review addresses current
understanding on the role of TAMs in breast carcinoma hallmarks and clarifies the
current scenario on pre-clinical drugs directed to tame pro-cancer TAMs.
PMID- 29952261
TI - Editorial: Metabolic and Hormonal Alterations in Neuro-Psychiatric Disorders.
PMID- 29952262
TI - Self-reported Instability in Knee Osteoarthritis: A Scoping review of Literature.
AB - Knee Osteoarthritis (OA) is a disabling musculoskeletal condition among the
elderly. Self-reported instability is one of the impairments associated with
osteoarthritis. A complete understanding of the self-reported instability in knee
OA is essential, to identify the best strategies for overcoming this impairment.
The focus of this scoping review is to provide an overview of evidence supported
information about the prevalence and other associated features of self-reported
instability in Knee OA. A broad search of the database PubMed with keywords such
as knee osteoarthritis and instability resulted in 1075 articles. After title
abstract and full-text screening, 19 relevant articles are described in the
review. Overall, there is less amount of published literature on this topic.
Studies reported prevalence rates of more than 60% for self-reported instability
in knee osteoarthritis, which causes functional deterioration and high fear of
falls. The most probable causative factors for self-reported instability in knee
OA were altered sensory mechanisms and decreased muscle strength. To conclude,
self-reported knee instability in knee OA requires thorough evaluation and
directed treatment with further studies providing rationalistic evidence-based
management strategies. The current literature regarding self-reported knee
instability is summarized, highlighting the research gaps.
PMID- 29952263
TI - The Protective Role of Crocus Sativus L. (Saffron) Against Ischemia- Reperfusion
Injury, Hyperlipidemia and Atherosclerosis: Nature Opposing Cardiovascular
Diseases.
AB - BACKGROUND: Reactive oxygen species and reactive nitrogen species, which are
collectively called reactive oxygen-nitrogen species, are inevitable by-products
of cellular metabolic redox reactions, such as oxidative phosphorylation in the
mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of
exogenous and endogenous substrate in endoplasmic reticulum, eicosanoid
synthesis, and redox reactions in the presence of metal with variable valence.
Among medicinal plants, there is growing interest in Crocus Sativus L. It is a
perennial, stemless herb, belonging to Iridaceae family, cultivated in various
countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India,
China, Egypt and Mexico. OBJECTIVE: The present study aims to address the anti
toxicant role of Crocus Sativus L. in the case of cardiovascular disease and its
role towards the cardioprotective role of Crocus Sativus L. MATERIALS AND
METHODS: An electronic literature search was conducted by the two authors from
1993 to August 2017. Original articles and systematic reviews (with or without
meta-analysis), as well as case reports were selected. Titles and abstracts of
papers were screened by a third reviewer to determine whether they met the
eligibility criteria, and full texts of the selected articles were retrieved.
RESULTS: Our review has indicated that scientific literature confirms the role of
Crocus Sativus L. as a cardiovascular-protective agent. The literature review
showed that Saffron is a potent cardiovascular- protective agent with a plethora
of applications ranging from ischemia-reperfusion injury, diabetes and
hypertension to hyperlipidemia. CONCLUSION: Literature findings represented in
current review herald promising results for using Crocus Sativus L. and/or its
active constituents as a cardiovascular-protective agent and in particular,
Crocus Sativus L. manifests beneficial results against ischemia-reperfusion
injury, hypertension, hyperlipidemia and diabetes.
PMID- 29952265
TI - In vitro anti-mycobacterial activity of three medicinal plants of Lamiaceae
family.
AB - BACKGROUND: Mycobacterium tuberculosis as an intracellular pathogen causes
tuberculosis (TB). Due to the long time required for treatment, hepatotoxicity of
drugs and also emergence of multidrug-resistant (MDR) and extremely drug
resistant (XDR) strains, TB is currently a major public health problem. Some
medicinal plants possess remarkable activity against Mycobacterium. Among them,
Lamiaceae family are of pharmaceutical interest because of their potential
antimicrobial properties. The aim of the study was to evaluate the in vitro
activities of Satureja rechingeri, Satureja khuzestanica and Zataria multiflora
against MDR M. tuberculosis and two non-tuberculous mycobacteria (NTM). The
recent patents on plant compositions (US7641919 B2, US7887860 B2, US 8865231 B2,
US 9345659 B2, WO 2014158797 A1 and WO 2014158877 A1) helped in selecting the
anti-mycobacterial drugs. METHODS: The essential oils were prepared by the
standard method. The confirmed strains were obtained from the microbial
collection of Tehran University of Medical Sciences. Minimum inhibitory
concentrations (MICs) of essential oils of plants against mycobacterial strains
were determined using standard broth microdilution method. RESULTS: MDR M.
tuberculosis was completely inhibited by Z. multiflora at 78MUg/ml concentration.
S. rechingeri and S. khuzestanica also showed same anti-mycobacterial activity
against MDR M. tuberculosis with MICs of 156 MUg/ml. The MICs of the essential
oils against M. tuberculosis H37Rv, M. kansasii and M. fortuitum were in the
range from 39 to 156 MUg/ml. CONCLUSION: The studied medicinal plants showed
notable effects against mycobacterial strains. Our results indicated that
utilization of Lamiaceae family can be helpful for treatment of mycobacterial
infections.
PMID- 29952264
TI - Trends in Vena Cava Filter Placement: An Analysis of Nationwide Inpatient Sample
Database Over an 11 Year Period.
AB - OBJECTIVES: There have been increasing concerns regarding inappropriate usage of
vena caval filters. Our study was done to analyze the current trends in vena
caval filter placement. METHODS: This study used the data from Nationwide
Inpatient Sample database for the years 2002- 2012 to identify patients with vena
caval filter placement. Trends in both therapeutic and prophylactic vena caval
filter use over the eleven years' period were analyzed. Multiple simple logistic
regression model was used to assess trends. RESULTS: The overall incidence of
vena caval filter placement increased from 2002 to 2012. The odds of vena caval
filter placement in 2012 were 1.340 (95% CI: 1.236, 1.453) times the odds of vena
caval filter placement in 2002. However, a downward trend was observed after the
year 2010. The odds of vena caval filter placement in 2012 were 0.854 (95% CI:
0.801, 0.911) times the odds in 2010. Similar trends were seen in both
therapeutic and prophylactic placements. The proportion of prophylactic vena
caval filter placements with indications of morbid obesity (P<0.0001), head
injury (P=0.0007), surgery of the eye, brain, spine or other major surgery
(P<0.0001) hemorrhage/bleeding (P=0.0046) significantly increased in 2012 when
compared to 2002. CONCLUSION: Vena caval filter placement rates have increased
significantly from 2002 to 2012 for both prophylactic and therapeutic
indications. However, there seems to be downward trend when comparing 2012 to
2010. Measures such as physician education and hospital audits can be done to
further bring down inappropriate vena caval filter placements.
PMID- 29952266
TI - Short Antimicrobial Peptides.
AB - BACKGROUND: After the era of serendipitous discovery of penicillin and outburst
in the discovery and development of highly efficient antibiotics, a surge in
resistance against the target specific drugs was observed, primarily due to a
combination of selective pressure of antibiotics use and spontaneous mutations.
As per the World Health Organization, antibiotic resistance is one of the
greatest threats to the mankind. OBJECTIVE: Short antimicrobial peptides (SAMPs)
can be considered as a viable therapeutic alternative to conventional antibiotics
in tackling resistant microbes. The ubiquitous nature of SAMPs combined with
their ability to act via non-specific modes of action, high activity against a
wide spectrum of drug-sensitive and drug-resistant microbes, and relative
insusceptibility against the development of resistance adds to their desirability
as new generation antibiotics. RESULTS: Due to the natural tendency of peptides
to get metabolized by proteolytic enzymes, modification of naturally occurring
SAMPs is desirable. The modifications can be done either by incorporating
unnatural or modified amino acids into the peptide chain or by protecting C and N
termini. The characteristic feature of SAMPs is their hydrophobicity and
cationicity, which aid in the effective killing of microbes by selectively
binding target and lysing the microbial cells with less deleterious effects on
the host cells as compared to AMPs and other conventional antibiotics.
CONCLUSION: Herein, we discussed the arsenal of short peptides and
peptidomimetics starting from the smallest unit possible - a dipeptide to a
decapeptide along with their activity profiles as antimicrobials. Recently,
various SAMPs have paved their ways from in vitro studies to clinical trials, as
evident from the most recent patent (EP1951194) on oral hygiene. This step by
step growth of SAMPs has restored the hope in peptide-based therapeutics, which
may prove an essential tool in eradicating antimicrobial resistance and tackling
various microbial infections.
PMID- 29952267
TI - Recent Progress on Neutralizing Antibodies against Hepatitis B Virus and its
Implications.
AB - BACKGROUND: Hepatitis B virus (HBV) infection remains a global health problem. As
"cure" for chronic hepatitis B is of current priority, hepatitis B immunoglobulin
(HBIG) has been utilized for several decades to provide post-exposure
prophylaxis. In recent years, a number of monoclonal antibodies (mAbs) targeting
HBV have been developed and demonstrated with high affinity, specificity, and
neutralizing potency. OBJECTIVE: HBV neutralizing antibodies may play potentially
significant role in the search for an HBV cure. In this review, we will summarize
the recently progress in developing HBV-neutralizing antibodies, describe their
characteristics and potential clinical applications. RESULTS AND CONCLUSION: HBV
neutralizing antibodies could be a promising alternative in the prevention and
treatment of HBV infection. More importantly, global collaboration and
coordinated approaches are thus needed to facilitate the development of novel
therapies for HBV infection.
PMID- 29952268
TI - A Review On Free Radicals and Antioxidants.
AB - Free radicals are generated in our body by several systems. A balance among free
radicals and antioxidants is an important matter for appropriate physiological
function. If free radicals become greater than the ability of the body to control
them, a case known as oxidative stress appears, as a result of that, a number of
human diseases spread in the body. Antioxidants can contribute in facing this
oxidative stress. The present review provides a brief overview on free radicals,
oxidative stress, some natural antioxidants and the relationship between them.
PMID- 29952269
TI - Effects of the Dopamine Stabilizer, Pridopidine, on Basal and Phencyclidine
Induced Locomotion: Role of Dopamine D2 and Sigma-1 Receptors.
AB - BACKGROUND: Pridopidine, a compound in clinical trials for Huntington's disease
treatment, was originally synthesized as a dopamine D2 receptor (D2R) ligand, but
later found to possess higher affinity for the sigma-1 receptor (S1R). However,
the putative contributions of D2R and S1R to the behavioral profile of acutely
administered pridopidine have not been investigated. OBJECTIVE: The present study
sought to compare the effects of acute pridopidine on wild-type vs. D2R and S1R
knockout mice, at high (60 mg/kg) and low (6 mg/kg) doses. METHOD: Pridopidine
effects on basal and phencyclidine-induced locomotor activity was measured in the
open field test. Additionally, the actions of pridopidine on prepulse inhibition
was measured in animals treated with saline or phencyclidine. RESULTS: Whereas
inhibition of spontaneous and phencyclidine-induced locomotion was readily
observed at 60 mg/kg pridopidine, neither locomotor stimulation in habituated
mice, nor any effects on prepulse inhibition were detected upon pridopidine
treatment. Surprisingly, inhibition of spontaneous locomotion was unaffected by
both D2R and S1R deletion. CONCLUSION: The present results suggest the
involvement of additional targets, besides D2R and S1R, in mediating locomotor
inhibition by pridopidine.
PMID- 29952270
TI - Long-term Treatment with Olanzapine Increases the Number of Sox2 and Doublecortin
Expressing Cells in the Adult Subventricular Zone.
AB - BACKGROUND & OBJECTIVE: Continuously active neurogenic regions in the adult brain
are located in the subventricular zone (SVZ) of the lateral ventricles and
subgranular zone of the hippocampal dentate gyrus. Neurogenesis is modulated by
many factors such as growth factors, neurotransmitters and hormones.
Neuropsychiatric drugs, especially antidepressants, mood stabilizers and
antipsychotics may also affect the origin of neuronal cells. METHOD: The purpose
of this study was to determine the effects of chronic olanzapine treatment on
adult rat neurogenesis at the level of the SVZ. The number of neuroblasts was
evaluated using immunohistochemical and fluorescent detection of sex determining
region Y-box 2 and doublecortin expressing cells. RESULTS & CONCLUSION: The
results indicate that olanzapine has proneurogenic effects on the adult rat SVZ,
as the mean number of sex determining region Y-box 2 and doublecortin-positive
cells increased significantly, while there was a similar tendency in the
subgranular zone. Collectively, these results suggest that long-term treatment
with olanzapine may stimulate neurogenic stem cell formation in the SVZ which
supports adult neurogenesis.
PMID- 29952271
TI - Voltage-gated sodium channels involve in sensory information processing.
AB - Action potential is a form of electric signaling responsibly for conducting
neural firing in organisms. Voltage-gated sodium channels (VGSCs) are key
molecules dedicating to the initiation and propagation of action potentials,
playing an indispensable role in processing excitable activity. The foundational
sensory of human covering vision, auditory, olfactory, taste and tactile perceive
the outer world rely on normal physiological function of VGSCs, which play as a
root dancing in music of life. The aberrant genetics and endogenous regulation of
VGSCs in most cases give rise to related clinical symptom such as
hyperpselaphesia, parosphresia, and so on. This review highlights recent advances
in the study of VGSCs in sensory systems which may facilitate the fresh
understanding of VGSCs in sensory information processing and provide a novel
pharmacological target for treatment of sensory system related clinical disease.
PMID- 29952272
TI - Oxidative Stress: Major Threat in Traumatic Brain Injury.
AB - BACKGROUND & OBJECTIVE: Traumatic Brain Injury (TBI) is one of the major causes
of mortality and morbidity worldwide. It represents mild, moderate and severe
effects of physical assault to brain which may cause sequential, primary or
secondary ramifications. Primary injury can be due to the first physical hit,
blow or jolt to one of the brain compartments. The primary injury is then
followed by secondary injury which leads to biochemical, cellular, and
physiological changes like blood brain barrier disruption, inflammation,
excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of
oxidative stress. Apart from this, there is also an immediate increase in
glutamate at the synapses following severe TBI. Excessive glutamate at synapses
in turn activates corresponding NMDA and AMPA receptors that facilitate excessive
calcium influx into the neuronal cells. This leads to the generation of oxidative
stress which further leads to mitochondrial dysfunction, lipid peroxidation and
oxidation of proteins and DNA. As a consequence, neuronal cell death takes place
and ultimately people start facing some serious disabilies. CONCLUSION: In the
present review we provide extensive overview of the role of reactive oxygen
species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.
PMID- 29952273
TI - Therapeutic Advancement in Alzheimer Disease: New Hopes on the Horizon?
AB - BACKGROUND & OBJECTIVE: Over the last two decades, Alzheimer disease (AD)
associated research has accomplished an overwhelming momentum, as it is one of
the major current healthcare issues in the developed world. AD is characterized
by the presence of Abeta mediated extracellular amyloid fibrils and tau-mediated
intracellular neurofibrillar tangles and reports have highlighted their
subsequent effects on neuronal synaptic activity, antioxidant response and
recently explored mitochondrial dysfunction. Additionally, recent reports have
demonstrated the mitochondrial dysfunction and associated physiological as well
as cellular alterations triggered by fibrillar structures inside the brain
tissue. Accumulated evidence indicated that mitochondrial dysfunction also plays
a detrimental role in AD pathogenesis and reduction in mitochondrial dysfunction
may provide an additional beneficial effect in AD patients. Currently available
drugs are ineffective in disease progression and more symptomatic while mechanism
oriented drug explorations have been intensively investigated. Therefore, search
for effective therapeutic approaches in Alzheimer disease has directed the
ongoing research more towards specific biomarker selection, physicochemical
properties of drugs and its subsequent interaction with target molecules.
CONCLUSION: In present review, we have comprised an overview of the therapeutic
advancement in Alzheimer disease with a prevalent hypothesis and current ongoing
putative therapeutic approaches to provide recent insights in AD pathogenesis.
PMID- 29952274
TI - Vitamin D Intake and Obesity in Occupational Asthma Patients and the Need for
Supplementation.
AB - BACKGROUND: Occupational asthma occurs in a significant number of adult unset
forms of asthma. Even after exposure cessation, persistent asthma is frequent.
Although recognized as important, nutrition, specifically vitamin D intake, was
rarely evaluated in occupational asthma. OBJECTIVE: To assess the vitamin D
intake in occupational asthma patients and the relation with body mass index, co
morbidities related to vitamin D deficit, lung function and quality of life.
RESULTS: We found a reduced vitamin D intake in both irritant and allergic
asthma, in obese and nonobese patients. The average intake in non-obese patients,
although higher, did not reach statistical significance. We also found lower
vitamin D intake in the mild asthma group versus the severe group, marginally
reaching the significance level (p=0.056) at the median test. Regression analysis
in asthma subpopulations revealed a different pattern of correlation, with a
stronger relationship between the BMI and the impact score in irritant asthma and
a closer link between vitamin D intake and symptoms score (p= 0.027) in the
allergic asthma group. CONCLUSION: The relation between obesity and vitamin D on
clinical scores and lung function seems to be different according to the asthma
phenotype. However, our study supports the usefulness of nutritional
interventions in all occupational asthma patients, targeting both the reduction
of the fat mass and the achievement of the recommended daily intake of vitamin D.
When analyzing the impact of the weight loss effect on asthma evolution, the
vitamin D status should also be considered as an influencer.
PMID- 29952275
TI - Comparative Study on Photodynamic Activation of Ortho-Toluidine Blue and
Methylene Blue Loaded Mesoporous Silica Nanoparticles Against Resistant
Microorganisms.
AB - AIMS AND BACKGROUND: Number of pathogenic microorganisms have been increasing
over the years, and so as these microorganisms been developing resistance against
various antibiotics. Antimicrobial photodynamic therapy (aPDT), also called
photodynamic inactivation, is emerging as a promising alternative to treatments
based on conventional antibiotics. Recent patents on structured silver mesoporous
silica nanoparticles having antimicrobial activity (WO2010/071831 A2),
photosensitiser modified core-shell structure nanocomposites (CN 103536935(A)),
and Chitosan-coated magnetic mesoporous silica nanoparticles (CN 104785214(A))
helped in selecting method of synthesis of MSN and photosensitizers. MATERIALS
AND METHODS: MSN were synthesised by Sol-Gel method and amino functionalised
(APTES). Methylene blue (MB) and ortho-toluidine blue (O-TB) were used as
photosensitisers. Different batches were synthesised. The final product was
characterised by using FTIR, BET, SEM, time resolved fluorescence. The
photosensitiser loaded MSN were illuminated by LED based lamp emitting red light
at 620+/- 20nm for different time lengths viz 15 min and 30 mins. Fluorescence
studies and antimicrobial assays were carried as per 72 well plate method I.P,
2014 using, gram negative E. coli (ATCC no. 8739), S. aureus (ATCC no. 7447) and
gram positive P .aeruginosa (ATCC no. 9027) pathogenic microorganisms. RESULTS:
MB and O-TB were successfully adsorbed on APTES functionalised MSN. Different
exposure time length of the photosensitisers to red light showed different zone
of inhibition. MB and O-TB loaded MSN showed significant increase in zone of
inhibition after irradiation as compared to MB and O-TB loaded on MSN without
exposure to light. CONCLUSION: MB and O-TB adsorbed on APTES functionalized
mesoporous silica nanoparticles were capable of efficiently inactivating E. coli,
P. aeruginosa, S. aureus bacteria upon exposure to red light (620+/- 20nm
wavelength) at a much lower concentration. Mesoporous silica nanoparticles played
an important role in aPDT due to its high surface area and porous structure. Also
APTES functionalization resulted in the pore expansion of MSN, thereby increasing
the loading capacity of the photosensitizer on MSN. From the results obtained it
can be concluded that O-TB loaded MSN showed higher activity against all three
gram negative microorganism as compared to that of MB.
PMID- 29952276
TI - Bougie-assisted cricothyroidotomy: Delphi-derived essential steps for the novice
learner.
AB - CLINICIAN'S CAPSULE What is known about the topic? The steps for performing a
bougie-assisted cricothyroidotomy (BAC) have not been systematically developed,
leading to instructional and performance variability. What did this study ask?
Can the modified Delphi process be used to establish the essential steps required
for BAC instruction? What did this study find? Using a modified Delphi
methodology, we developed a 17-item BAC checklist to guide instruction for novice
learners. Why does this study matter to clinicians? This checklist, developed by
expert consensus, can be used to improve consistency in training for this life
saving procedure.
PMID- 29952277
TI - Predicting antidepressant response by monitoring early improvement of individual
symptoms of depression: individual patient data meta-analysis.
AB - BACKGROUND: Improvement in depression within the first 2 weeks of antidepressant
treatment predicts good outcomes, but non-improvers can still respond or remit,
whereas improvers often do not.AimsWe aimed to investigate whether early
improvement of individual depressive symptoms better predicts response or
remission. METHOD: We obtained individual patient data of 30 trials comprising
2184 placebo-treated and 6058 antidepressant-treated participants. Primary
outcome was week 6 response; secondary outcomes were week 6 remission and week 12
response and remission. We compared models that only included improvement in
total score by week 2 (total improvement model) with models that also included
improvement in individual symptoms. RESULTS: For week 6 response, the area under
the receiver operating characteristic curve and negative and positive predictive
values of the total improvement model were 0.73, 0.67 and 0.74 compared with
0.77, 0.70 and 0.71 for the item improvement model. Model performance decreased
for week 12 outcomes. Of predicted non-responders, 29% actually did respond by
week 6 and 43% by week 12, which was decreased from the baseline (overall)
probabilities of 51% by week 6 and 69% by week 12. In post hoc analyses with
continuous rather than dichotomous early improvement, including individual items
did not enhance model performance. CONCLUSIONS: Examining individual symptoms
adds little to the predictive ability of early improvement. Additionally, early
non-improvement does not rule out response or remission, particularly after 12
rather than 6 weeks. Therefore, our findings suggest that routinely adapting
pharmacological treatment because of limited early improvement would often be
premature.Declaration of interestNone.
PMID- 29952279
TI - Sex in the laboratory: the Family Planning Association and contraceptive science
in Britain, 1929-1959.
AB - Scientific and medical contraceptive standards are commonly believed to have
begun with the advent of the oral contraceptive pill in the late 1950s. This
article explains that in Britain contraceptive standards were imagined and
implemented at least two decades earlier by the Family Planning Association,
which sought to legitimize contraceptive methods, practice and provision through
the foundation of the field of contraceptive science. This article charts the
origins of the field, investigating the three methods the association devised and
employed to achieve its goal of effecting contraceptive regulation. This was
through the development of standardized methods to assess spermicidal efficacy;
the establishment of quality, strength and manufacturing standards for rubber
prophylactics; and the institution of animal trials to ensure the safety of
specific contraceptives. The association publicized the results of its scientific
testing on proprietary contraceptives in its annual Approved List of
contraceptives. This provided doctors and chemists with a definitive register of
safe and effective methods to prescribe.
PMID- 29952278
TI - Collective quality improvement in the paediatric cardiology acute care unit:
establishment of the Pediatric Acute Care Cardiology Collaborative (PAC3).
AB - Collaborative quality improvement and learning networks have amended healthcare
quality and value across specialities. Motivated by these successes, the
Pediatric Acute Care Cardiology Collaborative (PAC3) was founded in late 2014
with an emphasis on improving outcomes of paediatric cardiology patients within
cardiac acute care units; acute care encompasses all hospital-based inpatient non
intensive care. PAC3 aims to deliver higher quality and greater value care by
facilitating the sharing of ideas and building alignment among its member
institutions. These aims are intentionally aligned with the work of other
national clinical collaborations, registries, and parent advocacy organisations.
The mission and early work of PAC3 is exemplified by the formal partnership with
the Pediatric Cardiac Critical Care Consortium (PC4), as well as the creation of
a clinical registry, which links with the PC4 registry to track practices and
outcomes across the entire inpatient encounter from admission to discharge.
Capturing the full inpatient experience allows detection of outcome differences
related to variation in care delivered outside the cardiac ICU and development of
benchmarks for cardiac acute care. We aspire to improve patient outcomes such as
morbidity, hospital length of stay, and re-admission rates, while working to
advance patient and family satisfaction. We will use quality improvement
methodologies consistent with the Model for Improvement to achieve these aims.
Membership currently includes 36 centres across North America, out of which 26
are also members of PC4. In this report, we describe the development of PAC3,
including the philosophical, organisational, and infrastructural elements that
will enable a paediatric acute care cardiology learning network.
PMID- 29952280
TI - Mid-term follow-up study of neonatal isolated aberrant right subclavian artery.
AB - BACKGROUND: Aberrant right subclavian artery is the most common congenital aortic
arch anomaly. There are a few reports concerning the clinical manifestations and
follow-up of this CHD detected by echocardiographic screening. METHODS: A total
of 1737 full-term neonates, with a male-to-female ratio of 900:837, received
echocardiographic screening. Neonates with or without isolated aberrant right
subclavian artery were studied during infancy. RESULTS: Among the 1737 cases, a
total of 15 (0.86%) female-predominant neonates, with a male-to-female ratio of
6:9, had isolated aberrant right subclavian artery. They were compared with 20
age- and gender-matched normal neonates. There were no significant differences in
maternal age, gestational age, or para gravity between the two groups, except for
birth size (birth length- and weight-for-age percentiles, p = 0.006 and 0.045,
respectively), which was smaller in the aberrant right subclavian artery group.
Although there were no significant differences in developmental history,
gastrointestinal, or respiratory symptoms, neonates with aberrant right
subclavian artery had a higher incidence of mild developmental delay and feeding
difficulty than normal infants (21 versus 0%, p = 0.061; 36 versus 20%, p =
0.264, respectively). The growth rates of body length and weight during infancy
were not significantly different between the two groups. CONCLUSIONS:
Echocardiography can be applied as a first-line investigation in the diagnostic
work-up for aberrant right subclavian artery. Neonates with aberrant right
subclavian artery had a smaller size at birth, although growth rates were not
significantly different from those of normal infants. This study does not support
an active surgical policy for asymptomatic infants with isolated aberrant right
subclavian artery. A larger study and longer follow-up of affected infants is
recommended.
PMID- 29952281
TI - Deformation Mechanisms in a Rolled Magnesium Alloy Under Tension Along the
Rolling Direction.
AB - The twinning and slip modes of a rolled magnesium alloy sheet were investigated
through quasi-in-situ tensile tests that were carried out along the rolling
direction at room temperature with a constant strain rate. Scanning electron
microscopy and electron backscattered diffraction observations were used to
identify activated twinning and slip systems. Schmid factors were calculated to
analyze different deformation modes. The analyses show that a small number of {10
12} tensile twins were present during deformation, and these twins resulted from
the accommodation of compression along the tensile direction. Post-deformation
examination revealed the dominance of prismatic slip.
PMID- 29952283
TI - Identification of Medicinally Used Flora Using Pollen Features Imaged in the
Scanning Electron Microscopy in the Lower Margalla Hills Islamabad Pakistan.
AB - The present study planned to assess the medicinally important plants in the lower
Margalla Hills of Islamabad, Pakistan using scanning electron microscopy of their
pollens. Both quantitative and qualitative characters of the pollens were
analyzed. The shapes of the pollen were prolate, spheroidal, elliptical, and
oblate. Exine sculpturing showed rugulate, scabrate, psilate gemmate, and
reticulate ornamentation. The people residing in the rural areas are thought to
depend, primarily, on medicinal plant resources for many health care needs. A
sample of 140 respondents was selected and interviewed by using a stratified
random sampling technique. Results showed that the local communities of lower
Margalla Hills are highly dependent on plants to treat various ailments, for
example, respiratory (28%), digestive (46%) nervous, circulatory and
dermatological problems (6% each), and reproductive problems (8%). The continuous
dependence of the local community on ethnomedicinally important plants has led to
serious degradation of the natural forest of lower Margalla Hills. Priority-based
conservation and sustainable use of these forest resources are necessary, and use
of alternative resources will also help in the forest conservation.
PMID- 29952282
TI - Hydrotalcite Can Prevent the Damaging Effects of Helicobacter Pylori on Gastric
Epithelial Cells.
AB - BACKGROUND: Helicobacter pylori is a major cause of gastric diseases including
gastric cancer. This study was aimed to explore whether hydrotalcite can inhibit
H. pylori infection of gastric epithelial cells. METHODS: the gastric epithelial
cell line GES-1 and the gastric cancer cell line BGC823 were infected with H.
pylori at multiplicities of infections (MOIs) of 50:1 and 100:1. Hydrotalcite was
added to cell cultures. Cell apoptosis and cell cycle analysis were performed to
measure the situation of cell growth. The main changes of cell ultrastructure
were observed by transmission electron microscopy. H. pylori cell adhesion was
observed by scanning electron microscopy. RESULTS: hydrotalcite could
significantly inhibit cell apoptosis of GES-1 and cell proliferation of BGC823
induced by H. pylori infection at an MOI of 50:1. Hydrotalcite treatment
protected gastric cells from H. pylori infection, and H. pylori adhesion to
gastric cells was reduced. However, hydrotalcite could not reverse damage induced
by H. pylori infection at an MOI of 100:1. CONCLUSION: hydrotalcite can protect
gastric cells from H. pylori infection when cell damage is not serious. It can
weaken the damage of cells induced by H. pylori and decrease H. pylori adhesion
to gastric cells.
PMID- 29952284
TI - Adaptive Modifications in Four Fish Species of the Genus Garra (Teleostei;
Cyprinidae) in Basistha River, Assam, India.
AB - This paper deals with the study of the surface morphology of barbels, upper lips,
and adhesive discs in four hill stream fish species collected from Basistha
River, a torrential river in Guwahati city, Assam, India. The four species
belonging to the genus Garra namely, Garra gotyla (Gray, 1830), Garra gravelyi
(Annandale, 1919), Garra stenorhynchus (Jerdon, 1849), and Garra nasuta
(McClelland, 1838) were collected from the same torrential habitat. These fish
revealed anatomical peculiarities in their barbels, lips, and adhesive discs
which are believed to help them in adapting to such habitats. Organs exhibiting
adaptive modifications (barbels, lips, and adhesive discs) were studied with the
scanning electron microscope. The study primarily revealed the presence of type I
and type II taste buds in the barbels, lips, and adhesive discs, and numerous
unculi surrounded by microridges in the upper lips and adhesive discs. A
cumulative, intercalated action of these organs enables these fish to adhere and
adapt to rocky, torrential streams. Special ability to adapt to these habitats
was reflected from the two types of taste buds (I and II) present in the barbels,
and the clustering of excrescencies bearing unculi in the lips and adhesive discs
of the fish.
PMID- 29952286
TI - Metastatic cutaneous apocrine carcinoma: a multidisciplinary approach
incorporating endocrine therapy.
PMID- 29952285
TI - BHLHE40, a third transcription factor required for insulin induction of SREBP-1c
mRNA in rodent liver.
AB - In obesity, elevated insulin causes fatty liver by activating the gene encoding
SREBP-1c, a transcription factor that enhances fatty acid synthesis. Two
transcription factors, LXRalpha and C/EBPbeta, are necessary but not sufficient
for insulin induction of hepatic SREBP-1c mRNA. Here, we show that a third
transcription factor, BHLHE40, is required. Immunoprecipitation revealed that
BHLHE40 binds to C/EBPbeta and LXRalpha in livers of rats that had fasted and
then refed. Hepatic BHLHE40 mRNA rises rapidly when fasted rats are refed and
when rat hepatocytes are incubated with insulin. Preventing this rise by gene
knockout in mice or siRNAs in hepatocytes reduces the insulin-induced rise in
SREBP-1c mRNA. Although BHLHE40 is necessary for insulin induction of SREBP-1c,
it is not sufficient as demonstrated by failure of lentiviral BHLHE40
overexpression to increase hepatocyte SREBP-1c mRNA in the absence of insulin.
Thus, an additional event is required for insulin to increase SREBP-1c mRNA.
PMID- 29952287
TI - Severe phenotype of junctional epidermolysis bullosa generalised intermediate
type caused by homozygous COL17A1:c.505C>T (p.Arg169*) mutation.
PMID- 29952288
TI - Stevens-Johnson syndrome associated with radiation recall dermatitis in a patient
treated with nivolumab.
PMID- 29952289
TI - Differential effects of two local anaesthetics on viability of skin keratinocytes
in vitro.
PMID- 29952290
TI - A case of acquired haemophilia A in a patient with bullous pemphigoid and review
of the Japanese literature.
PMID- 29952291
TI - Depigmented extramammary Paget's disease without histological dermal invasion
identified by multiple inguinal and pelvic lymph node metastases.
PMID- 29952292
TI - Multiple haemangiomas in TAFRO syndrome with atypical features of glomeruloid and
epithelioid haemangiomas.
PMID- 29952293
TI - Two cases of bullous pyoderma gangrenosum complicated by Epstein-Barr virus
infection.
PMID- 29952294
TI - Blood parameters in a population of blood donors are not affected by hidradenitis
suppurativa.
PMID- 29952295
TI - Clinical course of the first Japanese family with Marie Unna hereditary
hypotrichosis: a follow-up report.
PMID- 29952296
TI - Epidemiological trends of superficial fungal infections in Upper Egypt: a cohort
observational study.
PMID- 29952297
TI - Greater improvement in quality of life outcomes in patients using fixed
combination calcipotriol plus betamethasone dipropionate aerosol foam versus gel:
results from the PSO-ABLE study.
AB - BACKGROUND: Health-related quality of life (HRQoL) measures provide patient
centred evaluations of response to treatment. In the 12-week, Phase III PSO-ABLE
study, fixed-combination calcipotriol 50 MUg/g as hydrate (Cal) plus
betamethasone 0.5 mg/g as dipropionate (BD) aerosol foam was significantly more
effective for the treatment of psoriasis than Cal/BD gel. OBJECTIVE: To compare
HRQoL in mild-severe psoriasis vulgaris patients (involving 2-30% body surface
area) over 12 weeks of treatment with Cal/BD foam or gel. METHODS: HRQoL was
assessed using: Dermatology Life Quality Index (DLQI), EuroQoL-5D-5L-PSO (EQ-5D),
and Psoriasis QoL (PQoL-12) questionnaires (baseline, Weeks 4, 8 and 12); DLQI
score of 0/1 (range: 0-30) and weighted EQ-5D utility index score of 1 (range: 0
1) indicates there is no impact on a patient's QoL and perfect health,
respectively. Itch, itch-related sleep loss, and work impairment were also
assessed. RESULTS: In total, 463 patients were randomized to the study (Cal/BD
foam, n = 185; Cal/BD gel, n = 188; foam vehicle, n = 47; gel vehicle, n = 43).
Significantly more Cal/BD foam patients achieved DLQI scores of 0/1 at Weeks 4
(45.7% vs 32.4%; p = 0.013) and 12 (60.5% vs 44.1%; p = 0.003) than Cal/BD gel
patients. Cal/BD foam significantly improved EQ-5D utility index (0.09 vs 0.03;
p<0.001) and PQoL-12 scores (-2.23 vs -2.07; p = 0.029) from baseline to Week 4
versus Cal/BD gel. Itch, itch-related sleep loss, and work impairment improved
more with Cal/BD foam than gel. CONCLUSION: Cal/BD foam demonstrated greater
HRQoL improvement in patients with psoriasis than Cal/BD gel over 12 weeks of
treatment.
PMID- 29952299
TI - Predisposition to multi-drug hypersensitivity after administration of
mogamulizumab.
PMID- 29952298
TI - Decreased IL-10-producing regulatory B cells in patients with advanced mycosis
fungoides.
AB - BACKGROUND: Historically, B cells have been considered as positive regulators of
humoral immune responses. Specific B-cell subsets, however, negatively regulate
immune responses and are termed "regulatory B cells" (Bregs). Recently, Bregs
have been linked to not only inflammatory and autoimmune diseases, but also
malignancies via suppressing anti-tumour immunity. OBJECTIVES: To investigate the
involvement of Bregs in advanced mycosis fungoides (MF). MATERIALS & METHODS: The
frequency of CD19+CD24hiCD27+ memory B cells and CD19+CD24hiCD38hi transitional B
cells (which enrich IL-10-producing Bregs) was examined in peripheral blood from
patients with advanced MF (n = 11) and healthy controls (n = 9) by flow
cytometry. The frequency of IL-10-producing Bregs was also measured by flow
cytometry. The correlation between frequency or number of B-cell subsets and
disease severity markers was also analysed. RESULTS: The frequency of
CD19+CD24hiCD27+ B cells, CD19+CD24hiCD38hi B cells, and IL-10-producing B cells
was decreased in peripheral blood of advanced MF patients. The frequency and
number of these B-cell subsets inversely correlated with serum soluble IL-2
receptor and serum lactate dehydrogenase levels. CONCLUSIONS: The development of
IL-10-producing Bregs is impaired in patients with advanced MF and a decrease in
IL-10-producing Bregs may play an important role in the progression of advanced
MF.
PMID- 29952300
TI - Systemic therapy with calcitonin has positive clinical effects on systemic
sclerosis in patients with cutaneous manifestations.
AB - BACKGROUND: Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide
that plays an important role in the blood vessels of heart and peripheral
circulation, a lack of which may cause vasculopathies. OBJECTIVE: In this study,
the clinical course of disease, as well as the efficacy, side effects, and
patient satisfaction of systemic calcitonin therapy in patients with systemic
sclerosis (SSc), was evaluated. METHODS: Forty-nine patients received repetitive
intravenous calcitonin infusions as first-line treatment. The average number of
cycles was 12.2 +/- 10.3 over a period of 30 months (each cycle: 100 U/day over
10 days). Clinical examinations, laboratory tests, and organ imaging were
performed before the start of, and at regular intervals during therapy in order
to evaluate organ manifestations and the clinical course of the disease. In
addition, patients' own experiences of the therapy, side effects, and therapy
success were evaluated with standardized questionnaires. RESULTS: Over the course
of the treatment, seven patients experienced improvements in their condition with
a considerable reduction in digital ulceration and improved movement (14.3%).
Pulmonary function in seven patients improved during the therapy (14.3%). With
regards to side effects, nausea (41.7%), headaches (33.3%), fluctuations in blood
pressure (29.2%), and flushing (29.2%) were observed. Overall, 45.8% of patients
evaluated the therapy as good and 58.3% would undergo further courses of therapy
with calcitonin. CONCLUSIONS: Systemic calcitonin treatment seems to have
positive clinical effects on SSc and contributes to relieving symptoms,
especially in patients with cutaneous manifestations. No severe side effects were
reported during this study.
PMID- 29952301
TI - A screening programme for dermatologists as a guide to request psychological
consultation in routine clinical practice.
AB - BACKGROUND: The psychosocial impact of skin conditions is usually evaluated in
research settings. OBJECTIVES: To define predictors that can be used by
dermatologists to refer patients for psychological consultation or psychotherapy
using a simple screening instrument. MATERIALS & METHODS: A questionnaire to
evaluate possible anxiety and depression (12-item General Health Questionnaire
[GHQ-12]) was routinely used over a period of two months in an Italian
dermatological reference centre. RESULTS: Of 651 patients, 508 (78%) completed
the GHQ-12. Of the total sample, 35.2% scored 4 or more (psychological
consultation suggested), and 15.7% scored 7 or more (psychological consultation
recommended). Probable depression or anxiety was more frequent in women than in
men, in patients born in foreign countries, and in patients with leg ulcers,
pemphigoid, and psoriasis. CONCLUSION: Our results indicate that a simple
instrument may be useful for dermatologists to detect patients at risk of
psychological problems and subsequently refer them for psychological
consultation.
PMID- 29952302
TI - A randomized comparison of combined itraconazole and Nd:YAG 1064-nm laser vs
itraconazole alone for the treatment of cutaneous sporotrichosis.
PMID- 29952303
TI - A novel WRN mutation identified in a patient with Werner syndrome and acute
generalized exanthematous pustulosis.
PMID- 29952304
TI - Salivary cortisol testing: preanalytic and analytic aspects.
AB - Salivary cortisol assay, described for the first time almost forty years ago, has
not been expanding until the last decade. Its simplicity, non-invasiveness and
the easy repetition of sampling make it an analytical matrix of interest. Since
the publication of the recommendations of the American endocrinology society in
2008, salivary cortisol is recognized as one of the three main tests to screen
for Cushing's syndrome. In addition, salivary cortisone, the major metabolite of
salivary cortisol, still represents a severe potential interferent but could also
be a complementary analyte for indications where evaluation of cortisol secretion
is sought. Moreover, in the current context of practices and methods
harmonization, the problem of lack of standardization presents also for salivary
cortisol. This review briefly develops the three main tests of Cushing's syndrome
screening to explain the reasons for integrating the saliva test into this
screening. Then we will develop the variables that can influence salivary
cortisol from a pre-analytic, physiopathological and finally analytical point of
view.
PMID- 29952305
TI - Xanthoma disseminatum with rare extensive lesions.
PMID- 29952306
TI - The DRAGON study: biologic DRug survivAl in PortuGuese psOriasis patieNts.
PMID- 29952307
TI - A case of chronic prurigo successfully treated with omalizumab.
PMID- 29952308
TI - Rare Case of Both Left Atrial and Ventricular Compression by Dissecting Aortic
Aneurysm
PMID- 29952309
TI - The Relationship Between Tryptophan Hydroxylase-2 Gene with Primary Insomnia and
Depressive Symptoms in the Han Chinese Population
AB - Background: Insomnia often coexists with depression, and there is compelling
evidence for a genetic component in the etiologies of both disorders. Aims: To
investigate the relationship between exonic variant (rs4290270) in the tryptophan
hydroxylase-2 gene and primary insomnia and symptoms of depression in Han
Chinese. Study Design: Case-control study. Methods: This study included 152
patients with primary insomnia and 164 age- and gender-matched normal controls.
All patients were investigated by polysomnography for 2 consecutive nights. The
depressive symptoms were measured by using a 20-item Zung Self-rating Depression
Scale. Sleep quality was assessed with the Pittsburgh Sleep Quality index. The
genotypes of the TPH-2 gene polymorphism rs4290270 were determined by the
polymerase chain reaction-restriction fragment length polymorphism method.
Results: The genotype distributions of the tryptophan hydroxylase-2 gene
polymorphism rs4290270 were in Hardy-Weinberg equilibrium in both patients and
controls (p>0.05). The allele and genotype distributions of this variant were
comparable between patients and controls in all subjects and between genders (all
p>0.05). The impact of rs4290270 on self-rating depression scale score changes
was statistically significant (p=0.002), with carriers of the A/A genotype having
the highest self-rating depression scale score (mean +/- standard deviation:
52.73+/-12.88), followed by the A/T genotype (50.94+/-11.29, p=0.35) and the T/T
genotype (43.48+/-7.78, p<0.01), and this impact was more obvious in women
(p<0.001). Conclusion: The tryptophan hydroxylase-2 gene polymorphism rs4290270
may not be a susceptibility locus for primary insomnia in Han Chinese, but it may
be a marker of depressive symptoms.
PMID- 29952310
TI - Does FANCA Assist CENP-E in Architectural Organization of Chromosomes at Spindle
Equator?
PMID- 29952312
TI - Central Auditory Processing Disorders in Individuals with Autism Spectrum
Disorders
AB - The etiology and the underlying pathogenetic mechanisms of autism spectrum
disorders are still largely unknown. This article provides a comprehensive review
of the studies that are relevant to autism spectrum disorders and central
auditory processing disorders and also discusses the relationship between autism
spectrum disorders and central auditory processing disorders in the light of
recent studies on this subject, which may provide new pathways in a therapeutic
perspective. Several studies confirm that most of the individuals with an autism
spectrum disorder have some degree of sensory dysfunction related to disorders of
processing auditory, visual, vestibular, and/or tactile stimuli. Among these
studies, some have addressed central auditory processing disorders. There is an
increasing amount of effort for studies regarding the link between autism
spectrum disorders and central auditory processing disorders. Most of the studies
investigating central auditory processing disorders in patients with autism
spectrum disorders have used electrophysiological measurements such as mismatch
negativity and P300 event-related potentials. In addition to these, several
studies have reported deterioration in speech perception and expression in
patients with autism spectrum disorders, which may also be related to central
auditory processing disorders in this unique group of individuals.
PMID- 29952313
TI - 3D printing human induced pluripotent stem cells with novel hydroxypropyl chitin
bioink: scalable expansion and uniform aggregation.
AB - Human induced pluripotent stem cells (hiPSCs) are more likely to successfully
avoid the immunological rejection and ethical problems that are often encountered
by human embryonic stem cells in various stem cell studies and applications. To
transfer hiPSCs from the laboratory to clinical applications, researchers must
obtain sufficient cell numbers. In this study, 3D cell printing was used as a
novel method for iPSC scalable expansion. Hydroxypropyl chitin (HPCH), utilized
as a new type of bioink, and a set of optimized printing parameters were shown to
achieve high cell survival (>90%) after the printing process and high
proliferation efficiency (~32.3 folds) during subsequent 10 d culture. After the
culture, high levels of pluripotency maintenance were recognized by both
qualitative and quantitative detections. Compared with static suspension culture,
hiPSC aggregates formed in 3D-printed constructs showed a higher uniformity in
size. Using a novel dual-fluorescent labeling method, hiPSC aggregates in the
constructs were found more inclined to form by in situ proliferation rather than
multicellular aggregation. This study revealed unique advantages of non-ionic
crosslinking bioink material HPCH, including high gel strength and rapid
temperature response in hiPSC printing, and achieved primed state hiPSC printing
for the first time. Features achieved in this study, such as high cell yield,
high pluripotency maintenance and uniform aggregation provide good foundations
for further hiPSC studies on 3D micro-tissue differentiation and drug screening.
PMID- 29952314
TI - Perfectly conducting graphene electronic waveguide with curved channels.
AB - We theoretically investigate the electronic transport properties of curved
graphene waveguides by employing non-equilibrium Green's function techniques. We
systematically study the dependence of the confined waveguide modes on the
potential difference, the width of waveguide and side barrier. Through two
terminal electronic transport calculations, we show that the conductance of
confined waveguide modes is rather robust against the bending degree of
waveguide, in consistence with the band insensitivity to the side barrier. This
finding of the perfectly conducting channels strongly suggests the possibility of
applying the graphene waveguide in the design of low-power nanoelectronics.
PMID- 29952311
TI - The Novel and Minimally Invasive Treatment Modalities for Female Pelvic Floor
Muscle Dysfunction; Beyond the Traditional
AB - Pelvic floor dysfunction is a clinical entity that is prevalent among female
patients. Determining the exact underlying cause of pelvic floor dysfunction is
difficult, and surgical intervention for this clinical entity may be challenging.
Pelvic floor dysfunction can affect the quality of life of the patient by causing
stress urinary incontinence, pelvic organ prolapse, or both. Well-defined
surgical treatment options, minimally invasive approaches, and novel techniques
for the treatment of pelvic floor dysfunction have been recently introduced.
Here, we evaluated the management options available for patients with stress
urinary incontinence and pelvic organ prolapse. We searched Medline and EMBASE
databases for relevant articles by using the keywords "pelvic floor dysfunction,"
"minimally invasive procedures," "stress urinary incontinence," "pelvic organ
prolapse," and "novel techniques". Traditional treatment options for stress
urinary incontinence and pelvic organ prolapse are beyond the scope of our
review. Laparoscopic and robotic surgical treatments for pelvic floor dysfunction
continue to evolve and develop. These minimally invasive techniques will soon
replace open procedures. Alternative novel treatment modalities have also been
developed from novel human-compatible materials and are emerging as successful
treatments for stress urinary incontinence. The development of these various
treatment options has implications for future surgical practice in the field of
uro-gynecology.
PMID- 29952315
TI - Quantification of variations in intra-fraction motion of esophageal tumors over
the course of neoadjuvant chemoradiotherapy based on cine-MRI.
AB - To noninvasively quantify variation in intra-fraction motion of esophageal tumors
over the course of neoadjuvant chemoradiotherapy (nCRT) using 2D cine-magnetic
resonance imaging (MRI) series. Patients treated with nCRT for esophageal cancer
underwent six MRI scans. Scans were acquired prior to the start of nCRT, followed
by weekly MRI scans during nCRT. Cine-MRI series were acquired in the coronal and
sagittal plane (~1.6 Hz). To be able to quantify intra-fraction motion over a
longer time period, a second cine-MRI series was performed after 10 min. Tumor
motion was assessed in cranio-caudal (CC), anterior-posterior (AP) and left-right
(LR) direction. Motion patterns were analyzed for the presence of deep inhales
and tumor drift. A total of 232 cine-MRI series of 20 patients were analyzed. The
largest tumor motion was found in CC direction, with a mean peak-to-peak motion
of 12.7 mm (standard deviation [SD] 5.6), followed by a mean peak-to peak motion
in AP direction of 3.8 mm (SD 2.0) and in LR direction of 2.7 mm (SD 1.3). The CC
intra-fraction tumor motion can differ extensively between and within patients.
Deep inhales were present in six of 232 scans (3%). After exclusion of these
scans, mean CC peak-to-peak motion was12.3 mm (SD 5.2). Correction for tumor
drift showed a further reduction to 11.0 mm (SD 4.6). Despite correction for
tumor drift, a large variation in tumor motion occurred within patients during
treatment. Mean tumor drift during the 10 min interval between the two series was
1.5 mm (SD 1.8), with a maximum of 11.6 mm. Intra-fraction tumor motion was found
to be highly variable between and within patients with esophageal cancer over the
course of nCRT. Correction for deep inhales and tumor drift reduced peak-to-peak
motion. The stochastic nature of both deep inhales and tumor drift indicates that
real-time tumor motion management during radiotherapy is a prerequisite to safely
reduce treatment margins.
PMID- 29952316
TI - 3D elastic tensor imaging in weakly transversely isotropic soft tissues.
AB - We present herein 3D elastic tensor imaging (3D ETI), an ultrasound-based
volumetric imaging technique to provide quantitative volumetric mapping of tissue
elastic properties in weakly elastic anistropic media. The technique relies on
(1) 4D ultrafast shear wave elastography (SWE) at very high volume rate (e.g. >
8000 Hz, depending only on the imaging depth), (2) a volumetric estimation of
shear wave velocity using the eikonal equation and (3) a generalized 3D elastic
tensor-based approach. 3D ETI was first evaluated using numerical simulations in
homogeneous isotropic and transverse isotropic media. Results showed that 3D ETI
can accurately assess tissue stiffness and tissue anisotropy in weakly
transversely isotropic media (elastic fractional anisotropy coefficient <
0.34). Experimental feasibility was shown in vitro in a transverse isotropic
phantom. Quantification of the elastic properties by 3D ETI was in good agreement
with 2D SWE results performed at different orientations using a clinical
ultrafast ultrasound scanner. 3D ETI has the potential to provide a volumetric
quantitative map of tissue elastic properties in weakly transversely isotropic
soft tissues within less than 20 ms of acquisition for the entire imaged volume.
PMID- 29952317
TI - Equilibrium kinetics of self-assembling, semi-flexible polymers.
AB - Self-assembling, semi-flexible polymers are ubiquitous in biology and technology.
However, conflicting accounts of the equilibrium kinetics remain for such an
important system. Here, by focusing on a dynamical description of a minimal model
in an overdamped environment, I identify the correct kinetic scheme that
describes the system at equilibrium in the limits of high bonding energy and
dilute concentration.
PMID- 29952318
TI - Output and ([Formula: see text]) correction factors measured and calculated in
very small circular fields for microDiamond and EFD-3G detectors.
AB - The purpose of this work was to obtain [Formula: see text] factors for
microDiamond and EFD-3G detectors in very small (less than 5 mm) circular fields.
We also investigated the impact of possible variations in microDiamond detector
design schematics on the calculated [Formula: see text] factors. Output factors
(OF's) of 6 MV beams from TrueBeam linac collimated with 1.27-40 mm diameter
cones were measured with EBT3 films, microDiamond and EFD-3G detectors as well as
calculated (in water) using Monte Carlo (MC) methods. Based on EBT3 measurements
and MC calculations [Formula: see text] factors were derived for these detectors.
MC calculations were performed for microDiamond detector in parallel and
perpendicular orientations relative to the beam axis. Furthermore, [Formula: see
text] factors were calculated for two microDiamond detector models, differing by
the presence or absence of metallic pins. The measured OFs agreed within 2.4% for
fields ?10 mm. For the cones of 1.27, 2.46, and 3.77 mm maximum differences were
17.9%, 1.8% and 9.0%, respectively. MC calculated output factors in water agreed
with those obtained using EBT3 film within 2.2% for all fields. MC calculated
[Formula: see text] factors for microDiamond detector in fields ?10 mm ranged
within 0.975-1.020 for perpendicular and parallel orientations. MicroDiamond
detector [Formula: see text] factors calculated for the 1.27, 2.46 and 3.77 mm
fields were 1.974, 1.139 and 0.982 with detector in parallel orientation, and
these factors were 1.150, 0.925 and 0.914 in perpendicular orientation. Including
metallic pins in the microDiamond model had little effect on calculated [Formula:
see text] factors. EBT3 and MC obtained [Formula: see text] factors agreed within
3.7% for fields of ?3.77 mm and within 5.9% for smaller cones. Including
metallic pins in the detector model had no effect on calculated [Formula: see
text] factors. Our results show that microDiamond and EFD-3G detectors can be
used in very small (1.27-3.77 mm) fields once [Formula: see text] corrections
determined in this work are applied. Expected uncertainty of such measurements
will be in the range of 8%-2.5%.
PMID- 29952319
TI - The clinical target distribution: a probabilistic alternative to the clinical
target volume.
AB - Definition of the clinical target volume (CTV) is one of the weakest links in the
radiation therapy chain. In particular, inability to account for uncertainties is
a severe limitation in the traditional CTV delineation approach. Here, we
introduce and test a new concept for tumor target definition, the clinical target
distribution (CTD). The CTD is a continuous distribution of the probability of
voxels to be tumorous. We describe an approach to incorporate the CTD in
treatment plan optimization algorithms, and implement it in a commercial
treatment planning system. We test the approach in two synthetic and two clinical
cases, a sarcoma and a glioblastoma case. The CTD is straightforward to implement
in treatment planning and comes with several advantages. It allows one to find
the most suitable tradeoff between target coverage and sparing of surrounding
healthy organs at the treatment planning stage, without having to modify or
redraw a CTV. Owing to the variable probabilities afforded by the CTD, a more
flexible and more clinically meaningful sparing of critical structure becomes
possible. Finally, the CTD is expected to reduce the inter-user variability of
defining the traditional CTV.
PMID- 29952320
TI - Towards abdominal MRI-based treatment planning using population-based Hounsfield
units for bulk density assignment.
AB - This study investigates the dosimetric impact of using population-based
Hounsfield units (HUs) and ICRU-based HUs as a function of the number of tissue
segments for bulk density assignment toward MRI-based treatment planning in the
abdomen. To avoid potential geometric differences between CT and MR images, CT
images rather than MR images were chosen to simulate an MRI-only planning
scenario. A retrospective study was performed utilizing 18 patients that had
previously undergone stereotactic body radiation therapy for liver or pancreas
cancer. HU values in the CT datasets were collected for various tissue types, and
compared with the HUs derived from ICRU report 46. Doses were recalculated using
the fluence obtained from clinical plans and with (1) homogeneous assignment, (2)
ICRU-based HU assignment and (3) population-based HU assignment using three,
four, five, nine or ten tissue segments. Dose-volume metrics for targets and
organs-at-risk for all scenarios were compared with those obtained using the
clinical CT. For the planning target volume (PTV) D99.9%, the mean differences
from clinical CT plans were -2.1% +/- 3.9%, -0.6% +/- 0.3% and -0.1% +/-
0.3% for homogeneity, ICRU-HUs and population-HUs using ten tissue segments,
respectively. The population-HU method resulted in better dosimetric accuracy
compared to the ICRU-HU method (p-value < 0.05). The dosimetric accuracy of
homogeneity plans was comparable to that of both ICRU-HU and population-HU plans
when targets were far from the lungs but deteriorated when targets were close to
the lungs. As the number of tissue segments decreased, the dosimetric accuracy
for PTV D99.9% reduced for the population-HU method, from -0.1% for ten tissue
segments to -0.4% for three tissue segments, while no such dependence was
observed for the ICRU-HU method. Hence, to generate a clinically acceptable plan
when using MRI to synthesize CT in the abdomen for treatment planning, it might
be sufficient for electron density assignment with either the population-HU or
ICRU-HU method to only use three tissue segments.
PMID- 29952321
TI - Review on the progress in nuclear fission-experimental methods and theoretical
descriptions.
AB - An overview is given on some of the main advances in the experimental methods,
experimental results, theoretical models and ideas of the last few years in the
field of nuclear fission. New approaches have considerably extended the
availability of fissioning systems for the experimental study of nuclear fission,
and have provided a full identification of all fission products in A and Z for
the first time. In particular, the transition from symmetric to asymmetric
fission around 226Th, some unexpected structures in the mass distributions in the
fission of systems around Z = 80-84, and an extended systematics of the odd
even effect in the fission fragment Z distributions have all been measured
(Andreyev et al 2018 Rep. Prog. Phys. 81 016301). Three classes of model
descriptions of fission presently appear to be the most promising or the most
successful. Self-consistent quantum-mechanical models fully consider the quantum
mechanical features of the fission process. Intense efforts are presently being
made to develop suitable theoretical tools (Schunck and Robledo 2016 Rep. Prog.
Phys. 79 116301) for modeling the non-equilibrium, large-amplitude collective
motion leading to fission. Stochastic models provide a fully developed technical
framework. The main features of the fission-fragment mass distribution have been
well reproduced from mercury to fermium and beyond (Moller and Randrup 2015 Phys.
Rev. C 91 044316). However, limited computer resources still impose restrictions,
for example, on the number of collective coordinates and on an elaborate
description of the fission dynamics. In an alternative semi-empirical approach
(Schmidt et al 2016 Nucl. Data Sheets 131 107), considerable progress in
describing the fission observables has been achieved by combining several
theoretical ideas, which are essentially well known. This approach exploits (i)
the topological properties of a continuous function in multidimensional space,
(ii) the separability of the influence of fragment shells and the macroscopic
properties of the compound nucleus, (iii) the properties of a quantum oscillator
coupled to a heat bath of other nuclear degrees of freedom, (iv) an early freeze
out of collective motion, and (v) the application of statistical mechanics for
describing the thermalization of intrinsic excitations in the nascent fragments.
This new approach reveals a high degree of regularity and allows the calculation
of high-quality data that is relevant to nuclear technology without specifically
adjusting the empirical data of individual systems.
PMID- 29952322
TI - Faecal contamination and visual clarity in New Zealand rivers: correlation of key
variables affecting swimming suitability.
AB - Swimming is a popular activity in Aotearoa-New Zealand (NZ). Two variables that
strongly influence swimming suitability of waters are faecal contamination, as
indicated by the bacterium Escherichia coli, and visual clarity as it affects
aesthetics and safety with respect to submerged hazards. We show that E. coli and
visual clarity are inversely related overall in NZ rivers (R = -0.54), and more
strongly related in many individual rivers, while similar (but positive)
correlations apply also to turbidity. This finding, apparently reflecting co
mobilisation of faecal contamination and fine sediment, suggests that visual
clarity, measured or estimated from appearance of submerged features, should be a
valuable indicator of faecal contamination status and (more generally) swimming
suitability. If swimmers were to avoid river waters <1.6 m black disc visibility
(a long-established NZ guideline for swimming) they would also avoid microbial
hazards (E. coli <550 cfu/100 mL about 99% of the time in NZ rivers). However,
urban-affected rivers might sometimes be microbially contaminated when still
clear. Water management agencies should measure visual clarity together with E.
coli in river surveillance. Real-time information on swimming suitability could
then be based on continuous monitoring of turbidity locally calibrated to both
visual clarity and E. coli.
PMID- 29952323
TI - pH dependent octanol-water partitioning coefficients of microcystin congeners.
AB - Hazardous algal blooms can generate toxic compounds with significant health
impacts for exposed communities. The ubiquitous class of algal toxins known as
microcystins exhibits significant heterogeneity in its peptide structure, which
has been minimally studied, given the significant impact this has on
hydrophobicity, acid/base character and related environmental fate and health
effects. Octanol-water partition coefficients for the microcystin congeners MCLR,
MCRR, MCLY, MCLF, and MCLA were calculated over an environmentally and
physiologically relevant pH range. Microcystin-LR log(Kow) partition coefficient
values were found to be consistent with previously established literature values,
1.67 to -1.41 between pH 1 and 8. Microcystin RR was found to be pH insensitive
with a log(Kow) of -0.7. The remaining congeners exhibit similar pH dependence as
MCLR, with systematic increases in hydrophobicity driven by the introduction of
more hydrophobic residues to their variable amino acid region. The variation in
pH dependent hydrophobicity suggests increased propensity for bioaccumulation and
alternate environmental fates for differing microcystin forms, requiring further
investigation.
PMID- 29952324
TI - Microorganism levels in spray from warm-water bidet toilet seats: factors
affecting total viable and heterotrophic plate counts, and examination of the
fluctuations and origins of Pseudomonas aeruginosa.
AB - The objectives of this study were to conduct an appropriate microbial evaluation
of warm-water bidet toilet seats. Health-related advantages and disadvantages
have been associated with using warm-water bidet toilet seats, which are
classified according to the tank type, including tanks equipped with reservoir
water heaters and on-demand tankless systems equipped with an instantaneous water
heater. However, related bacterial research is sparse. Here, we performed a long
term survey of the behavior of microorganisms (i.e., the total viable count
(TVC), heterotrophic plate counts (HPCs), and Pseudomonas aeruginosa count) in a
university campus. We also examined the differences between the tank and on
demand types, and the origins of P. aeruginosa. A low TVC (<=1/mL) in the spray
waters from both on-demand and tank-type warm-water bidet toilet seats showed low
bacterial contamination, although there was an increase in HPC, i.e., growth of
biofilms, inside in the warm-water bidet toilet seats. When P. aeruginosa was
detected in spray water over an extended duration, the P. aeruginosa origin was
considered as either from feces or tap water. Collectively our findings
demonstrate that hygienic safety of warm-water bidet toilet seats is being
maintained overall.
PMID- 29952325
TI - Locally produced hydrogen sulphide detecting water quality test kits increase
household level monitoring in rural Tanzania.
AB - In developing countries, rural water sources have the highest levels of faecal
contamination but are the least monitored. Affordable field-based water quality
tests are needed. The presence of faecal indicator bacteria can be determined
with hydrogen sulphide (H2S) detecting tests, that are inexpensive and simple to
make locally. In rural Tanzania, a non-governmental organisation (NGO) designed,
produced and evaluated a new H2S water quality test kit. The H2S test results
correlated with log10 Escherichia coli densities from conventional water quality
tests. The production cost was US$ 1.10 and the test retailed for US$ 1.37. In
total, 433 tests were sold through local pharmacies and NGOs. Additionally, 165
WaSH education meetings, reaching 3,408 community members, were conducted with
the H2S test demonstrated in over half the meetings. Pre- and post-surveys of 294
meeting participants saw an increased reporting of household level water
treatment by 24%. The H2S test was widely accepted, with 94% of those surveyed
willing to buy the test in the future. International and national guidelines for
drinking water monitoring need to be amended to include locally produced H2S
water quality tests. This will enable households to monitor their own water
sources and make informed choices about water safety and treatment.
PMID- 29952326
TI - Consumer water quality evaluation of private and public drinking water sources.
AB - Private water wells have no requirements to be tested or monitored to ensure safe
drinking water quality, and yet those receiving their primary drinking water from
private supplies are more frequently confident that their tap drinking water is
safe. Using data from surveys administered in 2008 and 2014, this study assesses
public attitudes and perceptions regarding drinking water. This study examines
the results of a random sample survey of Texans to evaluate citizen awareness and
attitudes on water issues. Most respondents reported that they believe their
drinking water is of high quality, with 81.4% responding that they believe their
tap water is safe to drink. An even larger number, 92.1%, of those receiving
their water from private sources believe their tap water is safe. Conversely,
only 57.0% of respondents who consume bottled water as their primary source of
drinking water believe their tap water is safe to drink. Additionally, more than
65% of Texans receiving their primary drinking water from private supplies
(usually their private water well) have never had their water supply tested. A
large majority (81.3%) of those primarily receiving their drinking water from
private supplies believed groundwater in their area to be of good or excellent
quality.
PMID- 29952327
TI - Fate of Escherichia coli in dialysis device exposed into sewage influent and
activated sludge.
AB - Tracing the fate of pathogens in environmental water, particularly in wastewater,
with a suitable methodology is a demanding task. We investigated the fate of
Escherichia coli K12 in sewage influent and activated sludge using a novel
approach that involves the application of a biologically stable dialysis device.
The ion concentrations inside the device could reach that of surrounding solution
when it was incubated in phosphate buffered saline for 2 h. E. coli K12 above 107
CFU mL-1 (inoculated in distilled water, influent, activated sludge) were
introduced into the device and incubated in influent and activated sludge for 10
days. Without indigenous microorganisms, E. coli K12 could survive even with the
limited ions and nutrients concentrations in influent and activated sludge. E.
coli K12 abundance in influent and activated sludge were reduced by 60 and 85%,
respectively, after just 1 day. The establishment of microbial community in
wastewater played an important role in reducing E. coli K12. Bacteriophage
propagated in filtered influent or activated sludge when E. coli K12 was
introduced, but not in raw influent or activated sludge. The methodology
developed in this study can be applied in the actual environmental water to trace
the fate of pathogens.
PMID- 29952328
TI - A PVC-pipe device as a sanitary barrier for improving rainwater quality for
drinking purposes in the Brazilian semiarid region.
AB - We evaluate the behavior of a device designed to automatically divert and store
the first flush of harvested rainwater in cisterns. The first phase (PI) was
conducted with artificial precipitation in an experimental installation seeking
to identify how many millimeters of rainwater should be diverted to preserve the
rainwater quality. In the second phase (PII), we designed a PVC-pipe device to
store the first millimeter of rainwater, and tested it in field (a rural area in
Brazil) during two real rainfall events. In the third phase (PIII), the device
and a hand pump were assayed for two years using eight cisterns in a rural area
where people drink the rainwater. PI results indicated that the most significant
pollution of the rainwater is flushed with the first millimeter of rain, and
diversion promoted the removal of 98% and 100% of the total coliforms and
Escherichia coli, respectively. The bacteriological behavior was maintained in
the subsequent phases. The device was able to preserve the quality of the
rainwater most of the time, satisfying drinking requirements for the parameters
of turbidity and color. The satisfactory performance of the device was confirmed
in the field, behaving as a sanitary barrier for rainwater quality protection.
PMID- 29952329
TI - Assessment of drinking water suitability in low income rural areas: a case study
in Sixaola, Costa Rica.
AB - Vegas-Las Palmas is a rural settlement located in the southern Caribbean region
of Costa Rica on the border with Panama. Its population does not have access to
potable water, and inhabitants depend on water from wells at the water table
level to meet their needs. These wells lack basic infrastructure to protect this
water from contamination. In this study, water quality was evaluated at 12 wells
from 2014 to 2016 (n = 72). The results revealed high concentrations of faecal
coliforms and Escherichia coli with maximum values of 4.6 * 104 MPN/100 mL and
1.1 * 104 MPN/100 mL, respectively. In addition, maximum values of pH,
conductivity, turbidity, Ca, Mg, K, Fe, Mn, Cd and Pb were found to be outside
the standard limits (nationally and internationally) for potable water. Possible
sources of water contamination are associated with the geomorphological
characteristics of the area, as well as with hydrometeorological and
anthropogenic factors such as the lack of sewerage, the presence of latrines,
animals near the wells and the use of agrochemicals. The water quality was
heterogeneous among wells, and all of them were found to have conditions that
caused water to be unfit for human consumption.
PMID- 29952330
TI - In-situ electrochemical Fe(VI) for removal of microcystin-LR from drinking water:
comparing dosing of the ferrate ion by electrochemical and chemical means.
AB - Harmful algal blooms (HAB) release microtoxins that contaminate drinking water
supplies and risk the health of millions annually. Crystalline ferrate(VI) is a
powerful oxidant capable of removing algal microtoxins. We investigate in-situ
electrochemically produced ferrate from common carbon steel as an on-demand
alternative to crystalline ferrate for the removal of microcystin-LR (MC-LR) and
compare the removal efficacy for both electrochemical (EC) and chemical dosing
methodologies. We report that a very low dose of EC-ferrate in deionized water
(0.5 mg FeO42- L-1) oxidizes MC-LR (MC-LR0 = 10 MUg L-1) to below the guideline
limit (1.0 MUg L-1) within 10 minutes' contact time. With bicarbonate or natural
organic matter (NOM), doses of 2.0-5.0 mg FeO42- L-1 are required, with lower
efficacy of EC-ferrate than crystalline ferrate due to loss of EC-ferrate by
water oxidation. To evaluate the EC-ferrate process to concurrently oxidize
micropollutants, coagulate NOM, and disinfect drinking water, we spiked NOM
containing real water with MC-LR and Escherichia coli, finding that EC-ferrate is
effective at 10.0 mg FeO42- L-1 under normal operation or 2.0 mg FeO42- L-1 if
the test water has initial pH optimized. We suggest in-situ EC-ferrate may be
appropriate for sporadic HAB events in small water systems as a primary or back
up technology.
PMID- 29952331
TI - Assessing natural mineral water microbiology quality in the absence of cultivable
pathogen bacteria.
AB - Italian Directives recommend the good quality of natural mineral waters but
literature data assert a potential risk from microorganisms colonizing
wellsprings and mineral water bottling plants. We evaluated the presence of
microorganisms in spring waters (SW) and bottled mineral waters (BMW) samples.
Routine microbiological indicators, additional microorganisms like Legionella
spp., Nontuberculous mycobacteria (NTM) and amoebae (FLA) were assessed in 24 SW
and 10 BMW samples performing cultural and molecular methods. In 33 out of 34
samples, no cultivable bacteria >=10 CFU/L was found. Cultivable FLA were
detected in 50% of water samples. qPCR showed the presence of Legionella qPCR
units in 24% of samples (from 1.1 * 102 to 5.8 * 102 qPCR units/L) and NTM qPCR
units in 18% of samples (from 1 * 102 to 1 * 105 qPCR units/L). Vermamoeba
vermiformis and Acanthamoeba polyphaga were recovered respectively in 70% of BMW
samples (counts from 1.3 * 103 to 1.2 * 105 qPCR units/L) and 42% of SW samples
(from 1.1 * 103 to 1.3 * 104 qPCR units/L). Vahlkampfia spp. was detected in 42%
of SW and 70% of BMW samples (from 1.2 * 103 to 1.2 * 105 qPCR units/L).
Considering the presence of FLA, we underline the importance of a wider
microbiological risk assessment in natural mineral waters despite the absence of
cultivable bacteria.
PMID- 29952332
TI - Cryptosporidium parvum decay during air drying and stockpiling of mesophilic
anaerobically digested sewage sludge in a simulation experiment and oocyst counts
in sludge collected from operational treatment lagoons in Victoria, Australia.
AB - The inactivation of Cryptosporidium species oocysts during sewage sludge
treatment is important to protect human health when the residual biosolids are
applied to agricultural land. Quantifying the decay of Cryptosporidium species
during sludge treatment for microbiological assurance purposes is difficult if
low numbers are present in wastewater. The rate of decay of Cryptosporidium
parvum oocysts during solar/air drying treatment and in sludge stockpiles in
temperate environment conditions was simulated in laboratory inoculation
experiments using sludge sampled from a mesophilic anaerobic digester. Oocyst
numbers were also determined in settled lagoon sludge samples collected from
three operational rural wastewater treatment plants (WWTPs). C. parvum oocysts
were enumerated by immunomagnetic separation followed by staining with vital dyes
and examination by confocal laser scanning microscopy. An air-drying/storage
period equivalent to 11 weeks was required for a 1 log10 reduction of viable
oocysts inoculated into digested sludge. Oocyst viability in air-dried and stored
digested sludge decreased with time, but was independent of sludge desiccation
and dry solids (DS) content. No oocysts were detected in sludge samples collected
from the anaerobic digester, and the average concentration of oocysts found in
settled lagoon sludge from the rural WWTP was 4.6 * 102 oocysts/g DS.
PMID- 29952333
TI - A quantitative analysis of swimming pool recirculation system efficiency.
AB - The primary objective of this study was to conduct a quantitative analysis of the
hydraulic efficiency of a 1:25 bench-scale swimming pool and to determine whether
the recirculation efficiency could be increased by modifying parameters such as
turnover rate, inlet/out configuration, and extent of mixing within the pool.
Salt tracer studies were conducted using KCl to determine the residence time
distribution and describe the hydraulic characteristics of the pool. The results
indicated that the removal of the tracer always followed an exponential decay
curve, i.e. 63, 86, 95% for the first, second, and third turnover periods,
respectively. In the majority of experiments, the exponential decay rate matched
the inverse of the theoretical hydraulic detention time of the system. The
results showed that none of the investigated parameters had any significant
impact on the tracer removal efficiency. Increasing removal efficiencies of
current treatment technologies such as sand and cartridge filters from
approximately 25-90% would provide significant improvements in the rate of
removal of Cryptosporidium-sized particles. Improving the treatment efficiency
beyond 90% would have little additional impact, but further improvements could be
achieved by decreasing the system turnover rate.
PMID- 29952334
TI - Detection of Salmonella in the intestine of Hypostomus plecostomus from the upper
San Marcos River, Texas.
AB - The prevalence of salmonellae in the intestines of the invasive suckermouth
catfish Hypostomus plecostomus was assessed in the San Marcos River, just down
stream of its spring-fed headwaters. In 2014, H. plecostomus, sediment, and water
samples were collected during 15 sampling events. A combination of semi-selective
enrichment and quantitative polymerase chain reaction (qPCR) revealed the
presence of salmonellae in 45% of the fish intestines across the entire year,
with a prevalence range of 13-100% per sampling event. Repetitive element
sequence-based PCR (rep-PCR) and multi-locus sequence typing (MLST) revealed a
high diversity of salmonellae from fish intestine samples at individual sampling
times, single or multiple presence of rep-PCR patterns and serotypes within
individual fish, and identical rep-PCR patterns and serotypes for different fish
within and across sampling events. Overall, 15 serotypes were identified by MLST,
with a diversity range between one and seven serotypes per sampling event. Some
serotypes were retrieved only once, while others were detected more frequently. A
few serotypes were retrieved at several sampling times, nearly evenly distributed
over the entire sampling period. Prevalence and diversity were independent of
precipitation events, indicating the potential presence of environmental strains
that are capable of long-term persistence in the environment.
PMID- 29952335
TI - Sea water desalination and removal of iodine: effect on thyroid function.
AB - In Israel, about 55% of drinking water is derived from desalination (DSW) which
removes all iodine. A recent study from Israel demonstrated high rates of iodine
deficiency among school-aged children and pregnant women. There are concerns that
low iodine may lead to impaired thyroid function. However, to date, the impact of
consuming DSW on body iodine status has not been studied. The objective was to
assess whether the increased use of DSW is associated with increased rates of
hypothyroidism. Using data from a large health fund in Israel, we compared
proportions of patients with higher than normal thyroid stimulating hormone
(TSH), and lower than normal T3 and T4 levels before and after a massive
desalination project became operational in August 2013 in areas with high vs. low
use of DSW. Over 400,000 cases were compared in 2010-2013 vs. 2014-2016. Overall,
there was no increase in the proportion of individuals with higher than normal
TSH levels, or lower than normal T3 and T4 levels. In conclusion, in this
population-based study, following the introduction of DSW, there was no evidence
of increased incidence of low thyroid function tests, and the trends were similar
in both areas highly consuming, or not consuming, DSW.
PMID- 29952336
TI - Distribution of natural radionuclides and radon concentration in the riverine
environs of Cauvery, South India.
AB - Systematic studies were carried out to understand the distribution of natural
radionuclides in sediments and radon in water in the riverine environs of
Cauvery, one of the major rivers of South India. The activity of radionuclides in
the sediment was measured by gamma ray spectrometry. The radon emanation from the
sediment was measured by the sealed 'can technique' and the radon in the water
was measured using the RAD-7 instrument. The mean values of 40 K, 226Ra, and
232Th in the sediment samples were found to be 297.3 +/- 4.16 Bq kg-1, 75.1 +/-
2.64 Bq kg-1, and 85.5 +/- 2.62 Bq kg-1, respectively. The mean activity of
radon, radon exhalation rate, and radium content were found to be 135.68 Bq m-3,
327.1 mBq m-1 h-1, and 133.03 mBq kg-1, respectively. The radon in the water
ranged from 0.19 kBq m-3 to 1.40 kBq m-3. The hyper pure germanium gamma
spectroscopy measured via 226Ra activity and the radon activity measured by the
passive can technique showed good correlation. The mean value of radon in the
water was within the internationally recommended level. The sediment was
considered safe for the purpose of construction, except for some extreme values,
and the water was deemed safe for drinking.
PMID- 29952337
TI - Reservoirs of faecal indicator bacteria in well-head hand pumps in Bangladesh.
AB - The majority of the population of Bangladesh (90%) rely on untreated groundwater
for drinking and domestic use. At the point of collection, 40% of these supplies
are contaminated with faecal indicator bacteria (FIB). Recent studies have
disproved the theory that latrines discharging to shallow aquifers are the major
contributor to this contamination. In this study, we tested the hypothesis that
hand pumps are a reservoir of FIB. We sampled the handle, spout, piston and seal
from 19 wells in Araihazar Upazila, Bangladesh and identified that the spout and
seal were reservoirs of FIB. These findings led to our recommendation that well
spouts be regularly cleaned, including the removal of precipitated deposits, and
that the seals be regularly changed. It is envisaged that one or both of these
interventions will reduce the numbers of FIB in drinking water, thereby reducing
the burden of diarrhoeal disease in Bangladesh.
PMID- 29952338
TI - Cortisol cut-points for the glucagon stimulation test in the evaluation of
hypothalamic pituitary adrenal axis.
AB - Diagnosis of adrenal insufficiency requires evaluation by dynamic stimulation
tests. The insulin tolerance test (ITT) is accepted as the gold-standard test for
the evaluation of hypothalamo-pituitary-adrenal (HPA) axis but the test is
unpleasant and dangerous. Although it takes more time, glucagon stimulation test
(GST) is a good alternative to ITT. The primary aim of this study was to compare
the ITT and GSTs in the evaluation of HPA axe in patients with pituitary
disorders. We conducted a prospective study in which ITT and GST were performed
within 7 days in 81 patients. Serum cortisol was measured. We divided our
population in Group 1 (G1): Adrenal Insufficiency (Peak cortisol under ITT <200
ng/mL) and Group 2 (G2): normal response (Peak cortisol under ITT >200 ng/mL).
Receiver-operating characteristic (ROC) analysis was performed to identify the
thresholds for GST. The mean peak of cortisol under GST was not significantly
different from that obtained after ITT in the whole cohort (182.67 +/- 89.07
ng/mL vs. 179.75 +/- 79.01 ng/mL), and it was significantly reduced in patients
of G1 (p < 10-3). ROC curve analysis showed that the best diagnostic accuracy was
obtained with a peak cortisol cut-off to GST of 167 ng/mL (sensitivity, 89%;
specificity, 79%). Using this cut-off, 86.4% of the patients were correctly
classified. In our prospective series, GST is a potential accurate and safe
alternative test for the assessment HPA. Test-specific cut-offs should be applied
to avoid misinterpretation.
PMID- 29952340
TI - Erratum: Takeshi Ito, Yoko Hamazaki, Akifumi Takaori-Kondo, Nagahiro Minato
(2017) Bone Marrow Endothelial Cells Induce Immature and Mature B Cell Egress in
Response to Erythropoietin.
PMID- 29952341
TI - Monitoring Changes in Ejection Fraction in Patients With Heart Failure and Mid
Range Ejection Fraction.
PMID- 29952339
TI - Reconsideration of the evaluation criteria for bull ejaculated sperm motility in
the context of rotation.
AB - Progressive movement of spermatozoa has conventionally been regarded as a good
indicator of motility. However, bull spermatozoa exhibit two types of progressive
movement: progressive/planar movement without rotation and progressive/helical
movement with rotation. The aim of this study was to reconsider the evaluation
criteria of bull ejaculated sperm motility in the context of rotation. Here, we
compared the movement patterns of ejaculated spermatozoa with relatively high and
low protein kinase A (PKA)-mediated signaling activities, because sperm motility
is positively regulated by PKA-mediated signaling activities. We prepared sperm
samples with high and low PKA-mediated signaling activities by suspending
spermatozoa in media containing either the stimulator (NaHCO3) or inhibitor (KH
7) of adenylyl cyclase 10, and we then investigated movement patterns and
relative velocities using a microscopic high-speed camera and recording system.
In the control medium without NaHCO3 and KH-7, most spermatozoa exhibited
round/planar movement without rotation and asymmetrical bends in the principal
pieces. NaHCO3 significantly promoted changes in movement patterns from
round/planar movement to progressive/planar movement (without rotation) as well
as symmetrization of flagellar bends and increased relative velocities. KH-7
significantly increased spermatozoa exhibiting progressive/helical movement (with
rotation), decreased relative velocities, and symmetrized flagellar bends with a
reduction in their size. These indicate that progressive/planar movement (without
rotation) and fast movement characterize the movement patterns of bull ejaculated
spermatozoa with high PKA-mediated signaling activities. A sign of reduced PKA
mediated signaling activity is not only slow movement but also helical movement
(with rotation). Thus, it is beneficial to add a new parameter of "rotation" to
the evaluation criteria of bull ejaculated sperm motility.
PMID- 29952342
TI - Coronary Lesions in Takayasu Arteritis With Chronic Myelogenous Leukemia -
Intravascular Assessment With Optical Coherence Tomography and Fractional Flow
Reserve.
PMID- 29952343
TI - Overview of the 82nd Annual Scientific Meeting of the Japanese Circulation
Society - Futurability: Pioneering the Future of Circulatory Medicine.
AB - The 82nd Annual Scientific Meeting of the Japanese Circulation Society was held
in Osaka, Japan, on March 23-25, 2018, when the cherry blossoms were just opening
everywhere around the venue. This was the 5th Annual Scientific Meeting of JCS in
which a cardiovascular surgeon served as Congress Chairperson. The main theme of
this meeting was "Futurability: Pioneering the Future of Circulatory Medicine".
The word, futurability, is a neologism of future ability, because we now have to
contemplate what constitutes the essence of cardiovascular medicine, how it
should develop as medicine for future generations, and how its ability should be
displayed. The meeting was favored by splendid weather and the number of
participants was recorded as being higher than 18,700. There were heated and
profound discussions about the "futurability" of cardiology, cardiovascular
surgery, and heart team medical care as well, in every session. The meeting was
successfully completed and we sincerely appreciate the great cooperation and
support from all affiliates.
PMID- 29952344
TI - The association between birth weight and the risk of type 2 diabetes mellitus: a
systematic review and meta-analysis.
AB - Previous studies have shown a relationship between type 2 diabetes mellitus and
birth weight. We performed this meta-analysis to resolve the problem of
inconsistent results. We conducted a literature search of PubMed, Embase and the
Cochrane Library using "Diabetes Mellitus, Type 2," "Birth Weight," and some
related free words. Twenty-one studies were included in accordance with inclusion
and exclusion criteria, involving a total of 313,165 participants and 22,341 type
2 diabetes mellitus cases. A modified version of the Newcastle-Ottawa Scale was
used to evaluate the methodological quality of studies included. We used Review
Manager 5.3 for data merging and statistical analysis. Results were expressed as
odds ratio (OR) and 95% confidence interval (95% CI). The risk of diabetes with
low birth weight (<2,500 g) was higher than that with birth weight >=2,500 g, (OR
= 1.51, 95% CI: 1.43, 1.58). Compared with normal birth weight (2,500-4,000 g),
low birth weight, but not high birth weight, increased the risk of diabetes (OR =
1.41, 95% CI: 1.26, 1.58). There is a negative association between birth weight
and the future risk of type 2 diabetes mellitus.
PMID- 29952345
TI - The importance of wild gecko as a source of human Salmonella infection.
AB - A total of 201 wild geckos from the region of Mekong Delta, Vietnam were
collected to determine the viable number and survival period of Salmonella in
their feces. Of the 101 samples examined, 24 (23.8%) were Salmonella positive.
These 24 geckos excreted Salmonella in their feces in a range of 1 to 8.6 log
CFU/g with a mean of 4.5 +/- 3.2 log CFU/g. Among the Salmonella serovars,
Salmonella Weltevreden was the most predominant serovar (37.5%). Moreover,
Salmonella could survive for 6 weeks in gecko feces at room temperature in
Vietnam. These results indicate that the wild gecko seems to play an important
role as a reservoir for Salmonella and a source of Salmonella infection in humans
in Southeast Asian countries.
PMID- 29952346
TI - Thermo and halo tolerant laccase from Bacillus sp. SS4: Evaluation for its
industrial usefulness.
AB - Laccases are unable to oxidize the non-phenolic components of complex lignin
polymer due to their less redox potential (E0). Catalytic efficiency of laccases
relies on the mediators that potentiates their oxidative strength; for breaking
the recalcitrant lignin. Laccase from Bacillus sp. SS4 was evaluated for its
compatibility with natural and synthetic mediators. (2 mM). It was found that
acetosyringone, vanillin, orcinol and veratraldehyde have no adverse effect on
the laccase activity up to 3 h. Syringaldehyde, p-coumaric acid, ferulic acid and
hydroquinone reduced the enzyme activity >=50% after 1.0 h, but laccase activity
remained 100 to ~120% in the presence of synthetic mediators HBT (1
Hydroxylbenzotrizole) and ABTS. (2,2'-azino-bis (3-ethylbenzothiazoline-6
sulphonic acid) after 3 h. MgSO4 and MnSO4 (40 mM) increased the enzyme activity
3.5 fold and the enzyme possessed >=70% activity at a very high concentration. (2
M) of NaCl. The enzyme retained 40-110% activity in the presence of 10% DMSO
(dimethylsulfoxide), acetone, methanol and ethyl acetate. On the other hand,
CuSO4 (100 MUM) induced the laccase production 8.5 fold without increasing the
growth of bacterial cells. Laccase from SS4 appropriately decolorized the indigo
carmine (50 MUM) completely in the presence of acetosyringone (100 MUM) within 10
min and 25% decolorization was observed after 4 h without any mediator.
PMID- 29952347
TI - Fish Intake and Death From Pulmonary Embolisms Among Japanese Men and Women - The
Japan Collaborative Cohort (JACC) Study.
AB - BACKGROUND: Numerous studies have reported the association of cardiovascular risk
factors with pulmonary embolism (PE), but the association of dietary factors,
especially fish intake, with the risk of PE has not been fully
established.Methods and Results:Using a prospective design, we studied the risk
of PE mortality in relation to fish intake in 90,791 community-dwelling men and
women in Japan aged 40-79 years. The hazard ratios (HRs) and 95% confidence
intervals (CIs) for PE death were estimated using the Cox proportional hazards
model. Compared with participants in the lowest fresh fish intake group (<1
time/month), the HRs (95% CIs) for PE death for those in the other intake groups
were 0.35 (0.08-1.59) for 1-2 times/month, 0.19 (0.05-0.69) for 1-2 times/week,
0.20 (0.06-0.74) for 3-4 times/week, and 0.18 (0.05-0.66) for fish intake every
day. In addition to these findings, compared with the participants in the lowest
10% of omega3 polyunsaturated fatty acid intake, those in the other groups had a
60-76% lower risk of PE death. CONCLUSIONS: Fresh fish intake, even 1-2
times/week, is associated with a lower risk of death from PE among Japanese men
and women.
PMID- 29952348
TI - Autonomic Function and QT Interval During Night-Time Sleep in Infant Long QT
Syndrome.
AB - BACKGROUND: Sudden infant death syndrome mainly occurs during night-time sleep.
Approximately 10% of cases are thought to involve infants with long QT syndrome
(LQTS). Autonomic function and QT interval in night-time sleep in early infancy
in LQTS infants, however, remain controversial.Methods and Results:Holter
electrocardiography was performed in 11 LQTS infants before medication in early
infancy, and in 11 age-matched control infants. Control infants were re-evaluated
in late infancy. The power spectral density was calculated and parasympathetic
activity and sympathovagal balance were obtained. Electrocardiograms of a
representative hour during night-time sleep, daytime sleep, and daytime activity,
were chosen and QT/RR intervals were manually measured. LQTS infants had
significantly lower parasympathetic activity and higher sympathovagal balance
during night-time sleep than control infants in early infancy. These autonomic
conditions in early infancy were significantly depressed compared with late
infancy. Corrected QT interval (QTc) during night-time sleep (490+/-20 ms) was
significantly longer than that in daytime sleep (477+/-21 ms, P=0.04) or daytime
activity (458+/-18 ms, P=0.003) in LQTS infants, and significantly longer than
that during night-time sleep in controls. CONCLUSIONS: A combination of the
longest QTc and autonomic imbalance during night-time sleep in early infancy may
be responsible for development of life-threatening arrhythmia in LQTS infants.
Critical cases should be included in future studies.
PMID- 29952349
TI - Outcomes of Pulmonary Embolectomy for Acute Pulmonary Embolism.
AB - BACKGROUND: Acute pulmonary embolism (PE) is a major threat to the health and
lives of hospitalized patients. This study was conducted to clarify the real
world outcomes of pulmonary embolectomy.Methods and Results:Retrospective
investigation of 355 patients who underwent pulmonary embolectomy for acute PE
was conducted using the Japanese Cardiovascular Surgery Database. Risk factors
for operative death within 30 days after pulmonary embolectomy and major adverse
cardiovascular events (MACE), including operative death, postoperative stroke and
postoperative coma, were analyzed. Cardiopulmonary resuscitation (CPR) was
required preoperatively in 27.6%, and preoperative veno-arterial extracorporeal
membrane oxygenation was performed in 26.5%. Urgent or emergency operation was
performed in 93% of patients. Operative mortality rate was 73/355 (20.6%).
Incidence of MACE was 97/355 (27.3%). In univariate analysis, preoperative
predictors of death were obesity, renal dysfunction, chronic obstructive
pulmonary disease, liver injury, recent myocardial infarction, shock, refractory
shock, CPR, heart failure, inotrope use, poor left ventricular function,
preoperative arrhythmia and tricuspid regurgitation. In multivariate analysis,
independent risk factors for operative death were heart failure (P=0.013), poor
left ventricular function (P=0.007), and respiratory failure (P=0.001). Poor left
ventricular function (P=0.033), preoperative CPR (P=0.002) and respiratory
failure (P=0.007) were independent risk factors for MACE. CONCLUSIONS: The
outcomes of pulmonary embolectomy were acceptable, considering the urgency and
preoperative comorbidities of patients. Early triage of patients with
hemodynamically unstable PE is important.
PMID- 29952350
TI - Detection of chromosome abnormalities using current noninvasive prenatal testing:
A multi-center comparative study.
AB - Noninvasive prenatal testing (NIPT) is increasingly recognized and utilized in
the antenatal care field. In the current study, we aimed to evaluate the clinical
application and compare test outcomes of two generations of currently used NIPT
techniques for detecting fetal chromosome abnormalities in a high-risk prenatal
population. A total of 7,252 pregnant women were included from twenty-one
hospitals from January 2015 to September 2017. A maternal blood sample of each
participant was collected for fetal DNA sequencing. Group I received a first
generation NIPT sequencing technique to detect chromosome aneuploidies, and Group
II received a second generation NIPT sequencing technique to detect subchromosome
abnormalities. An abnormal NIPT result was reported in 0.90% (44/4,868) of the
women in Group I and 2.68% (64/2,384) in Group II. In Group I, seventeen (17/37,
45.95%) women with suspected fetal aneuploidy received amniocentesis, which
confirmed 100% (10/10) of positive trisomy 21 samples, 100% (1/1) of trisomy 18,
100% (1/1) of sex chromosome abnormality, 0% (0/2) of trisomy 16, 0% (0/2) of
trisomy 13, and 0% (0/1) of trisomy 20 and 13. In Group II, aneuploidy accounted
for 46.88% (30/64) of the abnormal results. Five underwent amniocentesis and
three had an abnormal result, including two cases of trisomy 21 and one case of
chromosome 5p deletion syndrome. Whereas one case of 46,XN,del(16q11.2-q22.3) and
another case of 46,XN,dup(Xp22.31) were considered as normal. NIPT is a quick and
reliable screening method for detecting fetal chromosome aneuploidies and
subchromosome deletions/duplications. Challenges remain for the comprehensive
clinical application of NIPT.
PMID- 29952351
TI - Long non-coding RNA Linc00312 modulates the sensitivity of ovarian cancer to
cisplatin via the Bcl-2/Caspase-3 signaling pathway.
AB - Chemotherapy is one of the main treatments for ovarian cancer (OC). Cisplatin
combined with paclitaxel is a commonly used chemotherapy regimen. However,
effective cancer therapy is hindered by a patient's resistance to cisplatin. The
mechanism that potentially leads to that resistance is unclear. The current study
examined the mechanism by which Linc00312 is involved in resistance to cisplatin
in OC. Quantitative real-time PCR (RT-qPCR) was used to test for expression of
Linc00312 in freshly frozen tissue samples of OC and in SKOV3 and SKOV3/DDP
cells. In situ hybridization was performed to examine the distribution of
Linc00312 expression in paraffin-embedded histological sections that were
sensitive or resistant to cisplatin. The cell counting kit-8 assay was used to
detect cell viability. Flow cytometry was used to measure cell apoptosis. RT-qPCR
was performed to confirm changes in expression of MDR1, MRP1, Bcl-2, Bax, Caspase
3, and Caspase-9 mRNA. Levels of MDR1, Bcl-2, Bax, Caspase-3, and Caspase-9
protein were detected with Western blotting. Experiments indicated that the
expression of Linc00312 decreased significantly in SKOV3/DDP cells compared to
that in SKOV3 cells. Upregulation of Linc00312 can considerably increase the
sensitivity of SKOV3/DDP cells to cisplatin, while down-regulation of Linc00312
has the exact opposite effect in SKOV3 cells. Linc00312 enhanced the sensitivity
of SKOV3/DDP cells to cisplatin by promoting cell apoptosis via the Bcl-2/Caspase
3 signaling pathway. These findings suggest that Linc00312 may be a promising
clinical strategy for the treatment of drug-resistant OC.
PMID- 29952352
TI - Serum containing Buyang Huanwu decoction prevents age-associated migration and
invasion of human vascular smooth muscle cells by up regulating SIRT1 expression.
AB - The migration and invasion of vascular smooth muscle cells (VSMCs) caused by
advanced aging play an important role in diffuse intimal thickening, facilitate
adverse arterial remodeling and contribute to the initiation and progression of
cardiovascular diseases. The inhibitory function of Buyang Huanwu decoction
(BYHWD) has been found on aortic intimal hyperplasia and VSMC proliferation, but
its effect on age-associated migration and invasion remains unknown. Here, we
used an in vitro angiotensin II (Ang II)-induced senescence model to study the
effects of serum containing BYHWD (BYHWS) on the migratory and invasive
capacities, matrix metalloprotease type 2 (MMP-2) expression and modulation of
sirtuin1 (SIRT1) signaling in human aorta VSMCs (HA-VAMCs). Our results showed
that BYHWS was able to inhibit Ang II-induced migration and invasion, with down
regulation of MMP-2. In addition, manipulation of SIRT1 by either over-expression
or siRNA knockdown ameliorated or promoted cellular migration and invasion,
respectively. Moreover, BYHWS reversed senescence-mediated decrease of SIRT1
levels and SIRT1 was required for BYHWS regulation on migration and invasion of
senescent HA-VAMCs. In summary, our data demonstrated that BYHWS suppressed the
migration and invasion of age-associated VSMC via an increase of the SIRT1 level,
which provides novel insights for the therapy of age-associated cardiovascular
diseases.
PMID- 29952356
TI - Analysis of gene copy number variations in patients with congenital heart disease
using multiplex ligation-dependent probe amplification.
AB - OBJECTIVE: At the molecular and cellular levels, heart development entails the
precise orchestration of genetic events such as the interplay of master
transcriptional regulators, signaling pathways, and chromatin remodeling. Recent
studies among patients with congenital heart disease (CHD) have shown the
importance of recurrent copy number variations (CNVs) in a significant number of
patients. Recurrent CNVs that span several genes may affect other important
organs, besides the heart. Because CHD may be the first presenting symptom in
such patients, the analysis of recurrent CNVs in the genomic regions containing
genes associated with CHD in patients referring to cardiology clinics may lead to
an early diagnosis and the treatment of extracardiac symptoms in these patients.
In this study, we aimed to screen CNVs of genomic regions including GATA4, NKX2
5, TBX5, BMP4, and CRELD1 genes and to analyse the 22q11.2 chromosomal region in
apparently nonsyndromic patients with cardiac septal defects. METHODS: Genomic
regions including GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes and the 22q11.2
chromosomal region were analyzed in apparently nonsyndromic 45 patients with
cardiac septal defects using the MLPA P-311 A2 Congenital Heart Disease kit.
Multiplex ligationdependent probe amplification (MLPA) is an established
technique for the detection of known CNVs. MLPA is substantially less expensive
than array CGH and is relatively simple to use for clinicians without specific
expertise in genomic technology; thus, MLPA could be used as a first-tier
screening assay. RESULTS: We screened 45 patients with cardiac septal defects for
CNVs using the MLPA P-311 A2 kit. We identified three CNVs (n=3/45, 6.66%) and
three 22q11 deletions. The CNVs were confirmed using fluorescence in situ
hybridization. CONCLUSION: Our study confirmed that the analysis of recurrent
CNVs using the MLPA assay within pediatric cardiology clinics can led to an early
syndrome diagnosis in nonsyndromic patients with CHD.
PMID- 29952357
TI - A descriptive analysis of abstracts presented at the Turkish National Cardiology
Congresses between 2011 and 2015.
AB - OBJECTIVE: The aim of this study was to investigate the scientific publication
performance of the abstracts presented at the annual Turkish National Cardiology
Congress (TNCC) between 2011 and 2015 and to analyze the variables associated
with publication. METHODS: The accepted abstracts of five congresses (2011-2015)
were screened using the title and names of all authors in English via PubMed and
Google Scholar databases. The parameters recorded included presentation type,
publication rate, time to publication, affiliated institution, journal name and
average impact factor, and average citation number per year for each publication.
RESULTS: A total of 2897 abstracts (966 oral presentations and 1931 poster
presentations) were accepted in five meetings and 23.4% (n=680) of these were
published in national or international peer-reviewed journals. Of the published
articles, 32.6% (n=222) were oral presentations and 67.4% (n=458) were poster
presentations. The mean time to publication of oral and poster presentations were
similar [9 (0-58) vs. 8 (0-62) months, p = 0.150]. According to the type of
institution, university hospitals had the highest ratio of publication (58.6%)
(p<0.001). All publications were published in 148 journals from 37 different
countries. The average citation number of publications was significantly higher
than the average impact factor of the journals [1.4 (0-30.1) vs. 1.29 (0.11
19.8), p<0.001]. CONCLUSION: Compared with other national-based literature in
other medical fields, the overall publication rate was found to be similar while
the time to publication was shorter. The significant difference between citation
number and impact factor may be interpreted as positive indicator in terms of
high level scientific value for cardiology publications presented in the TNCC.
PMID- 29952358
TI - Prognostic impact of renal dysfunction on long-term mortality in patients with
preserved, moderately impaired, and severely impaired left ventricular systolic
function following myocardial infarction.
AB - OBJECTIVE: The aim of this study was to investigate and compare the prognostic
impact of renal dysfunction (RD) at admission in patients with preserved,
moderately impaired and severely impaired left ventricular systolic function
following ST-elevation myocardial infarction (STEMI). METHODS: We included 2436
patients with STEMI treated with primary percutaneous coronary intervention
(pPCI). Patients presenting with cardiogenic shock and those on hemodyalisis were
excluded. According to the left ventricular ejection fraction (EF), patients were
divided in three groups: preserved left ventricular systolic function - EF >50%,
moderately impaired - EF=40%-50% and severely impaired left ventricular systolic
function-EF <40%. RD was defined as estimated glomerular filtration rate (eGFR)
<60 mL/min/1.73m2 at admission. The follow-up period was 6 years. RESULTS:
Preserved, moderately impaired and severely impaired systolic function were found
in 741 (30.5%), 1367 (56.1%) and 328 (13.4%) patients, respectively. RD was
present in 105 (14.2%) patients with preserved systolic function, 247 (18.1%)
patients with moderately impaired, and 120 (36.5%) patients with severely
impaired systolic function.Regardless of the presence of RD, 6-year mortality
rates in patients with preserved, moderately impaired, and severely impaired
systolic function were 2.7%, 5.2% and 31.1% respectively. Within each LVEF group,
patients with RD had a worse outcome, both in the short- and long-term. In the
Mulivariate Cox Analysis, RD remained an independent predictor of 6-year
mortality in patients with moderately (HR 2.52, 95% CI 1.54-3.78) and severely
impaired systolic function (HR 2.84, 95% CI 1.68-5.34), but not in patients with
preserved left ventricular systolic function (HR 0.59, 95% CI 0.14-1.41).
CONCLUSION: Although patients with RD had higher 6-year mortallity following
STEMI regardless of LVEF, RD at admission remained a strong independent predictor
for 6-year mortality only in patients with moderately and severely impaired left
ventricular systolic function.
PMID- 29952359
TI - Renal functions and prognosis in acute myocardial infarction. Concomitant left
ventricular dysfunction should have been taken into account.
PMID- 29952360
TI - Clinical study of stand-alone transthoracic echocardiography-guided percutaneous
occlusion of patent ductus arteriosus.
AB - OBJECTIVE: We aimed to investigate the feasibility and safety of stand-alone
transthoracic echocardiography-guided percutaneous occlusion of patent ductus
arteriosus (PDA) without the use of X-ray equipment. METHODS: From January to
December 2015, we performed stand-alone transthoracic echocardiography-guided
percutaneous PDA occlusion using an occluder delivered via a delivery sheath
introduced via femoral vein access without the use of X-ray equipment in 12 PDA
patients. RESULTS: PDA occlusion was successfully performed in all 12 patients.
The procedure duration ranged from 30 to 110 min (50.4+/-22.8 min), and the size
of the implanted occluder ranged from 12 to 20 mm (15.2+/-2.8 mm). No occluder
migration, residual shunt, or thrombotic complications were observed in the
perioperative period. There was no clinical death, hemolysis, infection, or
embolism during patients' hospitalization and the follow-up period. CONCLUSION:
Stand-alone transthoracic echocardiography-guided percutaneous PDA occlusion
without the use of X-ray equipment is a safe and effective procedure.
PMID- 29952361
TI - Pulmonary hypertension experience in an expert university hospital.
AB - OBJECTIVE: Pulmonary artery hypertension (PAH) is characterized by remodeling of
the small pulmonary arteries, leading to a progressive increase in pulmonary
vascular resistance and right ventricular failure. In this study, we aimed to
share our 10 years of experience dealing with pulmonary hypertension (PH) and
provide information in real-life settings in terms of demographics, clinical
course, PH subgroup distribution, and treatment patterns in patients with PAH in
a tertiary center. METHODS: In this retrospective, single-center, observational
study, we screened the patients who applied to PH outpatient clinic of Istanbul
University Institute of Cardiology due to the suspicion of PAH between 2008 and
2017. While group 1, 4, and 5 PH patients were included, group 2 and 3 PH
patients were excluded from the study. RESULTS: Our study group comprised 162
patients (115 females, 71%). The female:male ratio was 2.4. The mean age was 52+/
16 years. Most (86.4%) of the patients were in group 1 PH (PAH). The rest (13.6%,
n=22) of the patients were in group 4 PH (chronic thromboembolic PH). In group 1
PH, 45.7% of patients (n=64) were classified as having idiopathic PAH (IPAH)
after excluding the alternative diagnosis using PH diagnostic algorithm. The
remaining 54.3% of group 1 PH patients (n=76) had various diseases that caused
PAH, which is called associated PAH (APAH); APAH group included PAH associated
with congenital heart diseases (n=70), connective tissue disorders (scleroderma,
n=4) and portal hypertension (n=2). CONCLUSION: Our data provides important
information in real-life settings in terms of demographics, clinical course, PH
subgroup distribution, and treatment patterns in patients with PAH in a reference
tertiary center in Turkey.
PMID- 29952362
TI - A retrospective study on children with pulmonary arterial hypertension: A single
center experience.
AB - OBJECTIVE: The aim of this study was to evaluate children with pulmonary arterial
hypertension (PAH) regarding epidemiological characteristics, clinical status
with respect to the WHO functional class (WHO-FC), prognostic factors, and
efficacy of medical treatment. METHODS: A retrospective evaluation of 41 patients
with PAH was made in the Pediatric Cardiology Unit, Gazi University Medical
Faculty, between February 2006 and October 2015. RESULTS: Of the 41 patients
included in this study, 51.2% were female. The median age was 60 months at first
evaluation. The median follow-up was 60 months. At the start of the treatment,
43.9% patients were receiving combined drug therapy, and this rate increased to
60.9% by the last evaluation. The median time of adding a new medication to the
therapy was 20 months. The 1- and 5-year survival rates were 94% and 86%,
respectively. At the time of diagnosis, only pro-brain natriuretic peptide
(proBNP) levels were associated with mortality (p=0.004), but at the last
evaluation, 6-min walking test, proBNP and uric acid levels, and WHO-FC were also
associated with survival (p=0.02, p=0.001, p=0.002, and p=0.05, respectively).
CONCLUSION: With current treatment choices in experienced centers, positive
results are obtained with respect to the functional status and survival rates of
patients with PAH. At the time of diagnosis, only proBNP had a prognostic value,
whereas at the last evaluation, WHO-FC, 6-min walking test, proBNP, and uric acid
were reported prognostic factors. For preventing rapid progression, determination
of factors that have an effect on prognosis, in particular, is extremely
important.
PMID- 29952363
TI - Clinical implications from the European Heart Rhythm Association consensus
document on antiarrhythmic drug therapy.
AB - The recently published consensus document by the European Heart Rhythm
Association presents a patient-tailored pharmacological antiarrhythmic treatment
approach targeting the arrhythmia mechanism. This document comprehensively
reviews the indications, side effects, and contraindications of antiarrhythmic
drugs. In this paper, we reviewed novel treatment concepts offered by the
consensus document.
PMID- 29952364
TI - Anemia in heart failure - from guidelines to controversies and challenges.
AB - Anemia associated with heart failure is a frequent condition, which may lead to
heart function deterioration by the activation of neuro-hormonal mechanisms.
Therefore, a vicious circle is present in the relationship of heart failure and
anemia. The consequence is reflected upon the patients' survival, quality of
life, and hospital readmissions. Anemia and iron deficiency should be correctly
diagnosed and treated in patients with heart failure. The etiology is
multifactorial but certainly not fully understood. There is data suggesting that
the following factors can cause anemia alone or in combination: iron deficiency,
inflammation, erythropoietin levels, prescribed medication, hemodilution, and
medullar dysfunction. There is data suggesting the association among iron
deficiency, inflammation, erythropoietin levels, prescribed medication,
hemodilution, and medullar dysfunction. The main pathophysiologic mechanisms,
with the strongest evidence-based medicine data, are iron deficiency and
inflammation. In clinical practice, the etiology of anemia needs thorough
evaluation for determining the best possible therapeutic course. In this context,
we must correctly treat the patients' diseases; according with the current
guidelines we have now only one intravenous iron drug. This paper is focused on
data about anemia in heart failure, from prevalence to optimal treatment,
controversies, and challenges.
PMID- 29952365
TI - Diffuse alveolar hemorrhage associated with ticagrelor therapy after percutaneous
coronary intervention.
PMID- 29952367
TI - Electrocardiographic clues for understanding J-wave syndromes.
PMID- 29952366
TI - Extreme example of early repolarization.
PMID- 29952368
TI - Inherited dilated cardiomyopathy in a large Moroccan family caused by LMNA
mutation.
PMID- 29952369
TI - Rupture of noncoronary sinus aneurysm into the mitral anterior leaflet and the
left ventricle.
PMID- 29952370
TI - Chronic aortic pseudoaneurysm of aortic root with occluded right coronary artery
after trauma: A case report.
PMID- 29952371
TI - Pediatric and adult patients with pulmonary hypertension and a challenging case.
PMID- 29952372
TI - Effect of modified Blalock-Taussig shunt anastomosis angle and pulmonary artery
diameter on pulmonary flow.
AB - OBJECTIVE: This study aimed to identify the best graft-to-pulmonary artery (PA)
anastomosis angle measuring pulmonary blood flow, wall shear stress (WSS), and
shunt flow. METHODS: A tetralogy of Fallot with pulmonary atresia computer model
was used to study three different modified Blalock-Taussig shunt (mBTS)
anastomosis angle configurations with three different PA diameter configurations.
Velocity and WSS were analyzed, and the flow rates at the right PA (RPA) and left
PA (LPA) were calculated. RESULTS: A 4-mm and 8-mm diameter of RPA and LPA,
respectively with vertical shunt angle produces the highest total flow. In the
RPA larger diameter than the LPA configutations, the left-leaning shunt produces
the lowest total PA flow whereas in the LPA larger diameter than the RPA
configuratios, the right-leaning shunt produces the lowest total PA flow.
Therefore, the shunt anastomosis should not be leaned through the narrow side of
PA to reach best flow. As the flow inside the shunt increased, WSS also increased
due to enhanced velocity gradients. CONCLUSION: The anastomosis angle between the
conduit and PA affects the flow to PA. Vertical anastomosis configurations
increase the total PA flow; thus, these configurations are preferable than the
leaned configurations.
PMID- 29952374
TI - Corrigendum: Quantifying the cooperative subunit action in a multimeric membrane
receptor.
AB - This corrects the article DOI: 10.1038/srep20974.
PMID- 29952373
TI - Perineal Ultrasound Versus Magnetic Resonance Imaging (MRI) Detection for
Evaluation of Pelvic Diaphragm in Resting State.
AB - BACKGROUND The aim of this study was to compare the consistency differences
between ultrasound and MRI detection methods and the reliability between 2
independent observers. MATERIAL AND METHODS Under 2 kinds of states - the resting
state and muscle contractions state - intra-class correlation coefficients (ICCs)
were calculated and the consistency of 2 diagnostic methods was evaluated by 2
independent observers. We also assessed the interscorer reliability of the 2
observers. RESULTS In terms of the evaluation of biological parameters of the
pelvic diaphragm, the consistency of the 2 diagnostic methods was moderate. The
ICC of pelvic diaphragm area was 0.55 (95% CI 0.35-0.71), anteroposterior
diameter was 0.48 (95% CI 0.28-0.64), and transverse diameter was 0.43 (95% CI
0.25-0.63). The ultrasound detection values of the perineal ultrasound were
significantly smaller than those of the MRI. In addition, these differences were
increased with the rise of the pelvic diaphragm area. CONCLUSIONS By evaluating
the pelvic diaphragm in patients with pelvic organ prolapse in the resting state,
it was preliminarily confirmed that the consistency of ultrasound and MRI was
only moderate. The comparison of these 2 diagnostic methods under the dynamic
muscle contraction state needs to be further explored.
PMID- 29952375
TI - Corrigendum: Deciphering the function of the CNGB1b subunit in olfactory CNG
channels.
AB - This corrects the article DOI: 10.1038/srep29378.
PMID- 29952376
TI - [Spine arrangement during work in sitting position and occurrence of pain among
dentists and medical assistants].
AB - BACKGROUND: Back pain is common among people working in the sitting position.
Quality of the sitting position depends among others on the standard of work
station. Dental units are built on the basis of contemporary ergonomic workplace
concepts, while medical assistant workstations are typically computer office
workstations. The purpose of the study was pain estimation in association with
the identification of the spine arrangements during sitting work with better and
worse ergonomic adjustment. MATERIAL AND METHODS: The study involved 80 women
working in the sitting position suffering from pain - 40 dentists working on
dental units with a higher ergonomic potential and 40 medical assistants working
on stations with lower ergonomic potential. The study included interviews, pain
assessment and working spine arrangements analysis using the ultrasonographic
measurement system. RESULTS: There were exceeds of work parameters in particular
segments of the spine observed in all examined persons. The relationship between
pain intensity and work parameters as frontal bending amplitude of lumbar spine
segment, transversal amplitude of cervical spine segment and transversal
amplitude of lumbar spine segment were observed in the group of dentists. There
was observed the relationship between pain severity and the values of sagittal
bending amplitude of cervical spine segment and thoracic spine segment in the
group of medical assistants. Other determinants of pain also have been
identified. CONCLUSIONS: Exceeded values of work parameters were observed amongst
subjects working both at the higher and the lower ergonomic potential work
stations. The working postures of people working in the sitting position are
similar only to their external characteristics. Pain depends on working position.
The pain intensity is determined by other factors: length of professional
experience, duration of the pain, the number of working hours per week, body mass
index (BMI). Med Pr 2018;69(5):509-522.
PMID- 29952377
TI - Correction: Noncompetitive homogeneous immunodetection of small molecules based
on beta-glucuronidase complementation.
AB - Correction for 'Noncompetitive homogeneous immunodetection of small molecules
based on beta-glucuronidase complementation' by Jiulong Su et al., Analyst, 2018,
143, 2096-2101.
PMID- 29952378
TI - The role of the multiconfigurational character of nitronyl-nitroxide in the
singlet-triplet energy gap of its diradicals.
AB - While technological applications demand the development of reliable computational
techniques and accurate experiments for the characterization of diradicals, these
species are still challenging systems for both theory and experiments. The
singlet-triplet energy gap, the J-term of the Heisenberg-Dirac-van Vleck spin
Hamiltonian, is the most significant quantity; its measurement and computational
evaluation may serve for understanding and controlling magnetism at the molecular
scale. In this framework, we report a study of three diradicals containing one or
two nitronyl-nitroxide species. Using Difference Dedicated Configuration
Interaction (DDCI) calculations, we investigate the multiconfigurational
character of the O-N-C-N-O fragment of this unit. We find that a computational
scheme that takes this nature into account is necessary to confidently obtain
reliable values of the spin-spin coupling J. In addition, we show that the
reduced DDCI2 scheme with a CAS(2,2) reference, which can reproduce experimental
data in some cases, provides quite poor results in the present context.
PMID- 29952384
TI - Formation of ozone by solid state reactions.
AB - We studied the isotopic composition of ozone formed at low (3-10 K) temperature
via O + O2 solid state reactions using a partially dissociated 16O/16O2 :
18O/18O2 = 1 : 1 mixture. The ozone ice has an isotopic abundance that differs
from the statistical one and from gas phase studies. Ozone formation is
influenced by the competition of the production of O2 (O + O or O + O3) vs. O3 (O
+ O2) and by the energy released in the O + O reaction. The exothermicity of the
O + O reaction helps to overcome the barrier of the O + O2 reaction. Heating the
ozone ice past 50 K brings about a transformation from amorphous to crystalline
ice. The formation of ozone on water ice yields a blue shift of IR bands, and the
yield of formed O3 increases up to the sample temperature of 100 K. When 18O/18O2
is deposited on H216O ice, formation of 18O18O16O is detected. We propose that
the exothermicity of the reaction 18O + 18O drives water dissociation (16O + H2)
followed by ozone formation (16O + 18O2 -> 16O18O18O).
PMID- 29952383
TI - Crystal-on-crystal chips for in situ serial diffraction at room temperature.
AB - Recent developments in serial crystallography at X-ray free electron lasers
(XFELs) and synchrotrons have been driven by two scientific goals in structural
biology - first, static structure determination from nano or microcrystals of
membrane proteins and large complexes that are difficult for conventional
cryocrystallography, and second, direct observations of transient structural
species in biochemical reactions at near atomic resolution. Since room
temperature diffraction experiments naturally demand a large quantity of purified
protein, sample economy is critically important for all steps of serial
crystallography from crystallization, crystal delivery to data collection. Here
we report the development and applications of "crystal-on-crystal" devices to
facilitate large-scale in situ serial diffraction experiments on protein crystals
of all sizes - large, small, or microscopic. We show that the monocrystalline
quartz as a substrate material prevents vapor loss during crystallization and
significantly reduces background X-ray scattering. These devices can be readily
adopted at XFEL and synchrotron beamlines, which enable efficient delivery of
hundreds to millions of crystals to the X-ray beam, with an overall protein
consumption per dataset comparable to that of cryocrystallography.
PMID- 29952385
TI - Thermodynamics of ionic liquid evaporation under vacuum.
AB - The low volatility of ionic liquids (ILs) is one of their most interesting
physico-chemical properties; however, the general understanding of their
evaporation dynamics under vacuum is still lagging. Here, we studied the
thermodynamics of IL evaporation by employing thermogravimetry (TG) measurements
under vacuum. The thermodynamic parameters of ILs, such as the evaporation onset
temperatures, enthalpies, entropies, saturation vapor pressures, and boiling
points were quantified by analyzing the TG data. The obtained evaporation
enthalpies (110-140 kJ mol-1) were higher than those of typical molecular
liquids, and the entropies (>88 J mol-1 K-1) suggested that they are exceptions
of the Trouton's rule. The obtained Clausius-Clapeyron equations demonstrated
that the saturation vapor pressures of ILs only depend on temperature. Further,
we derived the empirical equation for estimating the upper limit temperature of
the liquid phase of IL under given external pressures. Using the evaporation
behaviors of referential normal alkanes and charge-transfer complex and the
evaporation entropies of the ILs, the vaporized IL structure was
thermodynamically modelled. The ILs were found to evaporate as ion pairs, instead
of as individual ions or higher-ordered cluster structures. By comparing a series
of ILs with various cations and a fixed anion, it was found that the IL
evaporation dynamics under vacuum is strongly and systematically affected by
their chemical structures, charge balances between the cations and the anions,
molecular weights, and the higher-ordered structures including polar and non
polar regions. Our concept, measurement method, and equation can be extended to
other ILs and low-volatile liquids under vacuum, and help with the design of ILs
with higher thermal stabilities.
PMID- 29952387
TI - Facile one-pot synthesis of well-defined coaxial sulfur/polypyrrole tubular
nanocomposites as cathodes for long-cycling lithium-sulfur batteries.
AB - Well-defined core-shell structured coaxial sulfur/polypyrrole tubular
nanocomposites, polypyrrole nanotubes wrapped by uniform rough sulfur layers,
were fabricated as Li-S battery cathodes via a facile one-pot method. In the
designed structure, the polypyrrole backbone can facilitate the charge transport
and also restrain the soluble polysulfide diffusion, while the active sulfur
layer can efficiently react with Li+ assisted by the PPy nanotubes, and the
lithium polysulfides can be massively trapped by the PPy nanotubes during charge
discharge processes. The as-prepared coaxial sulfur/polypyrrole tubular
nanocomposites with a sulfur loading of 53.3% exhibited a high initial discharge
specific capacity of 1117 mA h g-1 with a remarkable cycling stability, retaining
692 mA h g-1 and 525 mA h g-1 after 200 cycles at a current density of 0.2C and
1C, respectively. Moreover, they expressed an excellent rate capability
performance, maintaining 470 mA h g-1 at a high current density of 2C.
PMID- 29952386
TI - Luminescent protein staining with Re(i) tetrazolato complexes.
AB - Within the general framework of our past and current studies dealing with the
investigation of the photophysical properties and the biological behavior of the
family of tetrazolato and tetrazole Re(i) complexes, we have endeavored to
investigate their potential in the luminescent staining of proteins purified by
acrylamide gel electrophoresis. With the aim to provide the first examples of
luminescent Re(i) complexes to be exploited for this specific purpose, we have
designed and prepared four new Re(i)-based species with the general formula fac
[Re(CO)3(N^N)(Tph)]2-/0, where Tph is the 5-(phenyl)tetrazolato anion and N^N is
in turn represented by bathophenanthroline disulfonate (BPS), bathocuproine
disulfonate (BCS) or by the SO3- free bathocuproine (BC). In this latter case,
the neutral complex fac-[Re(CO)3(BC)(Tph)] served as a model species for the
characterization of the former disulfonate complexes. Its cationic analogue fac
[Re(CO)3(BC)(Tph-Me)]+ was also prepared by a straightforward methylation
reaction. All complexes displayed bright phosphorescence in organic media and,
relative to their water solubility, the dianionic species fac
[Re(CO)3(BPS)(Tph)]2- and fac-[Re(CO)3(BCS)(Tph)]2- were also highly emissive in
aqueous solution. The sulfonate groups played a key role in promoting and
significantly enhancing the luminescent staining performances of both the Re(i)
complexes fac-[Re(CO)3(BPS)(Tph)]2- and fac-[Re(CO)3(BCS)(Tph)]2- for proteins.
Highlighting a response superior to that of Coomassie Blue and comparable to the
one obtained by the well-known silver staining method, these dianionic Re(i)
complexes could efficiently detect up to 50 ng of pure Bovine Serum Albumin
(BSA), as well as all proteins found in a Standard Protein Marker mix and from a
total protein extract. A lower but still good response for luminescent protein
staining was surprisingly obtained by employing the -SO3- free neutral and
cationic complexes fac-[Re(CO)3(BC)(Tph)] and fac-[Re(CO)3(BC)(Tph-Me)]+,
respectively. These preliminary results open up new possibilities for the further
widening of the use of Re(i)-based complexes as luminescent protein staining
agents.
PMID- 29952388
TI - Microrheology of DNA hydrogel gelling and melting on cooling.
AB - We present systematic characterisation by means of dynamic light scattering and
particle tracking techniques of the viscosity and of the linear viscoelastic
moduli, G'(omega) and G''(omega), for two different DNA hydrogels. These
thermoreversible systems are composed of tetravalent DNA-made nanostars whose
sticky sequence is designed to provide controlled interparticle bonding. While
the first system forms a gel on cooling, the second one has been programmed to
behave as a re-entrant gel, turning again to a fluid solution at low temperature.
The frequency-dependent viscous and storage moduli and the viscosity reveal the
different viscoelastic behavior of the two DNA hydrogels. Our results show how
little variations in the design of the DNA sequences allow tuning of the
mechanical response of these biocompatible all-DNA materials.
PMID- 29952389
TI - Defect-induced betavoltaic enhancement in black titania nanotube arrays.
AB - Utilizing high-energy beta particles emitted from radioisotopes for long-lifetime
betavoltaic cells is a great challenge due to their low energy conversion
efficiency (ECE). Here we report a betavoltaic cell fabricated using black
titania nanotube arrays (TiO2 NTAs) by electrochemical anodization and Ar
annealing techniques. The obtained samples show enhanced electrical conductivity
as well as Vis-NIR light absorption by the introduction of oxygen vacancy (OV)
and Ti3+ defects in reduced TiO2-x NTAs. A 20 mCi63 Ni source was assembled into
TiO2 NTAs to form a sandwich-type betavoltaic cell. By I-V measurements, the Ar
annealed TiO2 NTAs at 650 degrees C exhibited a maximum ECE of 3.65% with Voc =
1.13 V, Jsc = 103.3 nA cm-2, and Pmax = 37 nW cm-2. In comparison with air
annealed TiO2 NTAs, the enhancement of the betavoltaic effect in reduced TiO2-x
NTAs can be attributed to the suppression of e-h recombination induced by the
generation of OV and Ti3+ defects, serving as electron donors as well as electron
traps that not only contribute to the increase of electrical conductance, but
also facilitate the charge carrier separation.
PMID- 29952390
TI - M13 bacteriophage spheroids as scaffolds for directed synthesis of spiky gold
nanostructures.
AB - The spherical form (s-form) of a genetically-modified gold-binding M13
bacteriophage was investigated as a scaffold for gold synthesis. Repeated mixing
of the phage with chloroform caused a 15-fold contraction from a nearly one
micron long filament to an approximately 60 nm diameter spheroid. The geometry of
the viral template and the helicity of its major coat protein were monitored
throughout the transformation process using electron microscopy and circular
dichroism spectroscopy, respectively. The transformed virus, which retained both
its gold-binding and mineralization properties, was used to assemble gold colloid
clusters and synthesize gold nanostructures. Spheroid-templated gold synthesis
products differed in morphology from filament-templated ones. Spike-like
structures protruded from the spherical template while isotropic particles
developed on the filamentous template. Using inductively coupled plasma-mass
spectroscopy (ICP-MS), gold ion adsorption was found to be comparatively high for
the gold-binding M13 spheroid, and likely contributed to the dissimilar gold
morphology. Template contraction was believed to modify the density, as well as
the avidity of gold-binding peptides on the scaffold surface. The use of the s
form of the M13 bacteriophage significantly expands the templating capabilities
of this viral platform and introduces the potential for further morphological
control of a variety of inorganic material systems.
PMID- 29952391
TI - Prewetting dichloromethane induced aqueous solution adhered on Cassie
superhydrophobic substrates to fabricate efficient fog-harvesting materials
inspired by Namib Desert beetles and mussels.
AB - Namib Desert beetles harvest water from harsh environments by using their
hydrophilic-hydrophobic dorsal surfaces. Generally, Cassie-state superhydrophobic
materials are chosen as substrates to prepare bioinspired
(super)hydrophilic/(super)hydrophobic patterned surfaces. However, due to the low
adhesion and strong repellency, aqueous solution cannot be directly set on Cassie
superhydrophobic materials until the dropping volume is larger than 6.5 MUL.
Therefore, arranging a (super)hydrophilic substance on Cassie superhydrophobic
substrates to construct (super)hydrophilic/superhydrophobic patterned surfaces
still remains a challenge. In this work, by prewetting with dichloromethane
(DCM), the mussel-inspired hydrophilic and bio-adhesive dopamine solution (DA)
could be dripped onto a Cassie superhydrophobic Cu surface with an ultralow
volume of 0.1 MUL, whereby low surface tension DCM would "cloak" the high surface
tension DA. Along with DCM volatility, DA was adhered on the Cassie
superhydrophobic surface and would then self-polymerize into hydrophilic
polydopamine domains, thus hydrophilic/superhydrophobic patterned surfaces with
efficient water collection could be successfully developed inspired by Namib
Desert beetles and mussels. The bioinspired materials show the potential for real
world industrialization in a large scale, which is of great significance for
providing living security for those living in areas with no access to fresh
water.
PMID- 29952392
TI - Overexpression of the mitochondrial Mg channel MRS2 increases total cellular Mg
concentration and influences sensitivity to apoptosis.
AB - The mechanism of action of the mitochondrial Mg channel MRS2 and its involvement
in cell viability remain unclear. Deletion of MRS2 has been reported to abolish
Mg influx into mitochondria, to induce functional defects in mitochondrial
organelles, and to result in cell death. We evaluated whether MRS2 expression had
an impact on total Mg cellular content by inducing the overexpression of MRS2 in
HEK-293 cells. We observed a remarkable increase of total intracellular Mg
concentration in cells overexpressing MRS2 compared with control cells. In order
to investigate whether and in what manner the detected Mg increment was involved
in the MRS2 influence on cell viability, we treated MRS2-overexpressing cells
with two known apoptotic inducers. We found that cells overexpressing the MRS2
channel became less responsive to these pharmacological insults. Our experimental
evidence indicates that the MRS2 channel controls overall intracellular Mg
levels, the alteration of which might have a role in the molecular signaling
leading to apoptotic cell death.
PMID- 29952393
TI - Small molecule activation with divalent samarium triflate: a synergistic effort
to cleave O2.
AB - The divalent samarium triflate salt does not react with CO2 or water, but does
react with traces of O2 or N2O to form a tetrameric bis-oxo samarium motif. The
reaction with O2 is a 4e- reductive cleavage where the electrons are coming from
four different samarium centers. This highlights a rare synergistic effect for
cleaving O2, which has no precedent in divalent lanthanide complexes.
Additionally, the addition of CO2 to the tetrameric bis-oxo intermediate leads to
the formation of a tetrameric bis-carbonate samarium triflate. Thus, the
concomitant reaction of CO2 with traces of O2 leads to the same bis-carbonate
tetrameric assembly.
PMID- 29952395
TI - Bio-behavioral survey of syphilis in homeless men in Central Brazil: a cross
sectional study.
AB - The objective of this study was to investigate the prevalence and factors
associated with syphilis in homeless men in Central Brazil. It is a cross
sectional study conducted with 481 individuals attending four therapeutic
communities between October and December 2015. A structured interview was
conducted to collect sociodemographic data and risk factors for syphilis.
Rapid/point-of-care and VDRL tests were performed to determine exposure to
syphilis and the presence of active syphilis, respectively. Poisson regression
analysis was used to verify the risk factors associated with the outcomes
investigated. Of the study participants, 10.2% were reactive to the rapid test,
and 5.4% had active syphilis. At the multiple regression analysis, schooling
(adjusted prevalence ratio - APR: 0.89; p = 0.005), history of genital ulcer
(APR: 2.59; p = 0.002), STI history (APR: 1.97; p = 0.042), and sexual
intercourse under drug effects (APR: 1.60; p = 0.022) were independent factors
associated with lifetime syphilis. Also, history of genital ulcer (APR: 2.19; p =
0.019), STI history (APR: 1.74; p = 0.033) and number of sexual partners in the
last year (APR: 1.02; p = 0.044) were associated with active syphilis. The
prevalence of syphilis among homeless men was rather high, confirming the
vulnerability of this group to this infection. These results emphasize the need
for educational intervention, improvement of risk reduction programs,
availability of diagnostic tests, especially the rapid test, and treatment.
PMID- 29952396
TI - [Between protocols and subject: quality of hospital care in a hematology
service].
AB - The article presents partial results of a study at Hospital Edgar Santos,
Universidade Federal da Bahia (HUPES), Brazil, analyzing the service's experience
with improvement in quality of care within a context of hospital accreditation.
The article focuses on the hematology service and specifically its quality of
care and intersubjective processes. The study adopted a qualitative approach,
using interviews and observation. From the theoretical point of view, the work of
Campos, Cecilio, and Merhy acknowledge healthcare's complex nature and
micropolitical and intersubjective dimension and the capacity of health
professionals to produce meanings and practice creativity. To understand the
health professionals' processes of psychosocial linkage and subjective
mobilization, we drew on concepts from the French school of psychosociology
(Enriquez) and Dejours' psychodynamics of work. The analysis was organized along
three lines: psychosocial linkage and the imaginary of self-management; bonding
and affect: singularity of the subject's care and clinical case; real work and
the healthcare team. One of the main conclusions is the building of a self
management imaginary, expressed in shared projects, expectations, and some forms
of interpreting and operating reality, based on affectively invested
representations of autonomy and unity. Alongside technical elements such as
protocols, the article highlights professional judgment, proper to the
intersubjective dimension, fostering the singularity of care. In our view, the
real work in the patient care scene is traversed by adjustments that demonstrate
team cooperation.
PMID- 29952397
TI - Guidelines for early detection of breast cancer in Brazil. III - Challenges for
implementation.
AB - The objective of the current article is to present the main challenges for the
implementation of the new recommendations for early detection of breast cancer in
Brazil, and to reflect on the barriers and the strategies to overcome them. The
implementation of evidence-based guidelines is a global challenge, and
traditional strategies based only on disseminating their recommendations have
proven insufficient for changing prevailing clinical practice. A major challenge
for adherence to the new guidelines for early detection of breast cancer in
Brazil is the current pattern in the use of mammographic screening in the
country, which very often includes young women and a short interval between
tests. Such practice, harmful to the population's health, is reinforced by the
logic of defensive medicine and the dissemination of erroneous information that
overestimates the benefits of screening and underestimates or even omits its
harms. In addition, there is a lack of policies and measures focused on early
diagnosis of symptomatic cases. To overcome these barriers, changes in the
regulation of care, financing, and implementation of shared decision-making in
primary care are essential. Audit and feedback, academic detailing, and the
incorporation of decision aids are some of the strategies that can facilitate
implementation of the new recommendations.
PMID- 29952398
TI - Quality assessment of clinical guidelines for the treatment of obesity in adults:
application of the AGREE II instrument.
AB - There are various guidelines for the treatment of obesity, and thus the quality
of these clinical guidelines has become a matter of concern. The objective was to
describe and assess the quality of clinical guidelines for treatment of obesity
in adults. We collected several studies, dated from 1998 to 2016, produced by
different countries. The literature search included the National Guideline
Clearinghouse (NGC), Guidelines International Network (GIN), PubMed (MEDLINE),
Scopus, Web of Science, webpages of health institutions from different countries,
and search sites, with the criterion: "clinical guidelines for treatment of
obesity in adults and published until the 2016". The guidelines were assessed
with the Appraisal of Guidelines for Research & Evaluation (AGREE II), according
to the domains of the instrument. The search identified 21 guidelines: nine from
Europe, six from North America, three from Latin America, and one each from Asia
and Oceania and a transnational association. The Australian guideline had the
best assessment. Of the six guidelines with the highest scores, five had been
elaborated by the government sector responsible for the country's health. The
domains "scope and purpose" and "clarity of presentation" had the highest score.
Except for the Canadian guideline, the three guidelines drafted before the
elaboration of AGREE II had the worst quality. In the domain "stakeholder
involvement", only four guidelines (Australia, Scotland, France, and England)
mentioned patient participation. Guideline development and quality enhancement
are ongoing processes requiring systematic appraisal of the guideline production
process and existing guidelines.
PMID- 29952400
TI - [Determinants of patents in the life sciences and health sciences at federal
universities in Minas Gerais State, Brazil: an analysis of panel data for 1995
2016].
AB - In the 1990s, the development of microelectronics and communication technologies
spawned the information technology paradigm, characterized by an intensity of
information which, transformed into knowledge and innovation, plays a crucial
role for development. In order for this to occur, countries need to build
appropriate institutional arrangements. This led to the Triple Helix model for
systems innovation, which views innovation and technical progress in a Knowledge
Economy as the result of a complex set of relations between universities,
companies, and government. In this context, the current study aims to identify
the impact of knowledge production and public policies for the production of
patent applications by life sciences and health sciences researchers affiliated
with federal universities in the State of Minas Gerais, Brazil. The analysis
covered the years 1995 to 2016 and used econometric techniques in panel data.
According to the findings, educational factors (thesis supervision), economic
factors (technological products and the provision of technological services), and
political factors (legal framework, financial resources, and incentive policies)
impact the production of patent applications by the selected researchers. The
results reveal efforts by government, although incipient, in the attempt to
promote a technological leap.
PMID- 29952399
TI - [Urban-rural gradient in tobacco consumption and cessation patterns in Brazil].
AB - The degree of urbanization has been associated with both tobacco consumption and
quit rates. The current study aims to examine the importance of the urban-rural
context in the determination of tobacco consumption patterns and smoking
cessation. Data were used from the supplement of the Special Survey on Smoking
(PETab) from the 2008 Brazilian National Household Sample Survey (PNAD). The
sample included 14,420 individuals over 15 years of age, of whom 7,003 were
current smokers and 7,417 former smokers in the PETab. Smoking prevalence and
cessation rates were calculated. Individuals were stratified according to urban
and rural residence. Other sociodemographic variables were also analyzed: sex,
age bracket, race, and schooling. To explore the difference in smoking prevalence
and cessation rate for each stratum in the census situation, the data were
adjusted using a Poisson model. Smoking prevalence was higher in places less
influenced by the urban environment. Meanwhile, smoking cessation was higher in
more urbanized places. Smoking prevalence showed a decrease in consumption as the
population's urban characteristics increased (PR = 0.75 for eminently urban vs
eminently rural, p = 0.001). Smoking cessation trends showed that the more urban
population was more prone to quitting (PR = 1.22 for eminently urban vs eminently
rural, p < 0.001). The results point to the need to improve the effectiveness of
services for follow-up and encouragement of cessation in rural areas.
PMID- 29952401
TI - [Hospitalizations and deaths from drug poisoning and adverse reactions in Brazil:
an analysis from 2000 to 2014].
AB - In recent years, drug poisoning and adverse reactions have been an important
cause of hospitalization and mortality and a major public health issue. The aim
of this study was to describe trends in hospitalizations and deaths from drug
poisoning and adverse reactions from 2000 to 2014. Data were from the Mortality
Information System (SIM) and Information System on Authorizations for Hospital
Admissions of the Brazilian Unified National Health System (SIH-SUS), and the
study population was analyzed by sex, region of residence, and age bracket.
Events were defined according to ICD-10 codes. The analysis of trends in the
historical series used Prais-Winsten generalized linear regression with
correction for first order autocorrelation effect. Both the hospitalizations and
deaths during the study period showed upward trends. The analysis by regions
maintained the upward trends for both events in the South and Southeast regions.
Analysis according to age brackets showed downward trends in children under five
years in both events, upward trend in deaths in individuals over four years of
age, and an upward trend in hospitalizations in the age bracket from 20 to 59
years. Drug poisoning and adverse reactions contribute significantly to
hospitalizations and deaths in Brazil, and the SIM and SIH-SUS are data sources
with satisfactory quality for population-based studies on hospital morbidity and
mortality in the country.
PMID- 29952402
TI - Breakfast patterns and their association with body mass index in Brazilian
adults.
AB - The objective was to investigate the relationships between body mass index (BMI),
skipping breakfast, and breakfast patterns in Brazilian adults. We analyzed data
of 21,003 individuals aged between 20 to 59 from the Brazilian National Dietary
Survey 2008-2009. Breakfast was defined as the eating occasion between 5 and
10a.m. with the highest usual food consumption (exceeding 50Kcal/209.2kJ).
Dietary patterns were derived by the factor analysis of 18 food groups (usual
intake). Controlling for confounders linear regressions of BMI were used to
verify the associations considering the survey design. Skipping breakfast was not
associated with BMI. Three breakfast patterns were observed (48% variability):
Brazilian Northern (positive loading for meats, preparations with corn, eggs,
tubers/roots/potatoes, dairy products, savory snacks/crackers, fruit juices/fruit
drinks/soy-based drinks); Western (positive for fruit juices/fruit drinks/soy
based drinks, sandwiches/pizza, baked/deep-fried snacks, chocolate/desserts,
cakes/cookies) and Brazilian Southeastern (cold cut meat, milk, cheese,
coffee/tea, bread). The Brazilian Southeastern pattern was inversely associated
with BMI, while the Brazilian Northern pattern was directly associated with it.
Therefore, the results suggest a role for breakfast quality in the association
with BMI. Thus, a Brazilian Southeastern breakfast usual intake may be inversely
associated with BMI.
PMID- 29952403
TI - [Nutritional status and environmental and health conditions of Pataxo indigenous
children, Minas Gerais State, Brazil].
AB - To describe the nutritional status and the environmental and health conditions of
the Pataxo children from five villages of Minas Gerais State, Brazil. Among the
under 10 years old, weight and height/length were classified according to the
growth references of World Health Organization. Questionnaires evaluating
environmental conditions of the households and health conditions of under 5 years
old were based in the First National Survey of Indigenous People's Health and
Nutrition. Among the 70 children evaluated (93.3%), 34 were under 5 years old.
Nutritional deficits were not observed and overweight was registered for 11.4% of
the children. Most of the children (74.3%) lived in households with electric
energy, 95% in households with toilets and 52.9% in households that threw waste
in septic tanks. Six or more antenatal appointments were reported by 82.4% of the
mothers of the under five years old and 91.2% started the antenatal appointments
within the first trimester of pregnancy. Among the causes of hospitalizations in
the previous 12 months (23.5%), only one was due to diarrhea and none to
respiratory infection. Universal coverage was observed for the majority of the
vaccines. The absence of nutritional deficits among the Pataxo children may be
associated to better housing and sanitation conditions and coverage of basic
childhood health actions when compared to the conditions reported by the First
National Survey of Indigenous People's Health and Nutrition and related studies
with other specific indigenous peoples. The current study aims to back
discussions and measures to improve the nutritional status of indigenous children
in Brazil.
PMID- 29952405
TI - ERRATUM: Consumption of ultra-processed foods and socioeconomic position: a cross
sectional analysis of the Brazilian Longitudinal Study of Adult Health.
AB - [This corrects the article doi: 10.1590/0102-311X00019717].
PMID- 29952404
TI - Delays in access to care for abortion-related complications: the experience of
women in Northeast Brazil.
AB - Around 18 million unsafe abortions occur in low and middle-income countries and
are associated with numerous adverse consequences to women's health. The time
taken by women with complications to reach facilities where they can receive
appropriate post-abortion care can influence the risk of death and the extent of
further complications. All women aged 18+ admitted for abortion complications to
public-sector hospitals in three capital cities in the Northeastern Brazil
between August-December 2010 were interviewed; medical records were extracted (N
= 2,804). Nearly all women (94%) went straight to a health facility, mainly to a
hospital (76.6%); the rest had various care-seeking paths, with a quarter
visiting 3+ hospitals. Women waited 10 hours on average before deciding to seek
care. 29% reported difficulties in starting to seek care, including facing
challenges in organizing childcare, a companion or transport (17%) and
fear/stigma (11%); a few did not initially recognize they needed care (0.4%). The
median time taken to arrive at the ultimate facility was 36 hours. Over a quarter
of women reported experiencing difficulties being admitted to a hospital,
including long waits (15%), only being attended after pregnant women (8.9%) and
waiting for a bed (7.4%). Almost all women (90%) arrived in good condition, but
those with longer delays were more likely to have (mild or severe) complications.
In Brazil, where access to induced abortion is restricted, women face numerous
difficulties receiving post-abortion care, which contribute to delay and
influence the severity of post-abortion complications.
PMID- 29952406
TI - ?
AB - [This corrects the article doi: 10.1590/0102-311X00165716].
PMID- 29952407
TI - Dose titration model and correlative factors analysis in Chinese patients with
type-2 diabetes on basal insulin - results from an Observational Registry of
Basal Insulin Treatment study.
AB - INTRODUCTION: This study evaluates an insulin dose titration model and factors
that impact insulin dose adjustment in Chinese adults with type-2 diabetes, who
receive basal insulin in real-world settings. MATERIAL AND METHODS: A total of
19,894 patients from the ORBIT study were included. These patients were divided
into four groups, according to the type of insulin dose adjustment: no insulin
titration (group A), self-titration (group B), physician-led insulin titration
(group C), and combined physician and patient-led insulin titration (group D).
Data were collected and compared at baseline and after six months of treatment.
RESULTS: A total of 12,865 patients completed the visits and were included in the
analysis. Among these patients, 3187 (24.8%), 1971 (15.3%), 5165 (40.1%), and
2542 (19.8%) patients were included in groups A, B, C, and D, respectively. The
multivariate logistic regression analysis revealed that the duration of diabetes,
body mass index, microvascular complications, inpatient days, HbA1C level, and
self-monitoring of blood glucose (SMBG) were positively correlated with insulin
titration in group B, C, and D, compared with group A. The number of inpatient
days and outpatient visits were positively correlated with dose adjustment for
physician-led titration, while this was negatively correlated for self-titration.
Self-titration encouraged by physicians and home blood glucose monitoring were
positively correlated with self-titration and the combined physician and patient
led titration. CONCLUSIONS: High HbA1C level, SMBG, long disease duration,
microvascular complications, and the encouragement of physicians while initiating
insulin use prompt patients to perform dose adjustments in real-world settings.
PMID- 29952408
TI - Choosing the optimal method of anaesthesia in anterior resection of the rectum
procedures - assessment of the stress reaction based on selected hormonal
parameters.
AB - INTRODUCTION: The aim of this study was to compare hormonal stress responses
(changes in adrenaline, noradrenaline, and cortisol concentrations) to surgical
injury during total intravenous propofol anaesthesia and volatile anaesthesia
with sevoflurane in patients subjected to anterior resection of the rectum.
MATERIAL AND METHODS: The prospective randomised study included 61 patients
qualified for anterior resection of the rectum. The subjects were randomised into
two groups, based on the type of anaesthesia: 1) Group I (TIVA, n = 31),
administered total intravenous propofol anaesthesia, and 2) Group II (VIMA, n =
30), administered volatile induction and maintenance sevoflurane anaesthesia.
Serum concentra-tions of adrenaline, noradrenaline, and cortisol were determined
prior to surgery, during assessment of abdominal cavity, after resection of the
rectum, and 30 min and one day post-surgery. RESULTS: The two groups did not
differ significantly in terms of their haemodynamic parameters: heart rate and
arterial blood pressure. Compared to individuals subjected to TIVA, patients from
the VIMA group presented with significantly higher concentrations of adrenaline
during evaluation of the abdominal organs. No significant intergroup differences
were found in terms of intra- and postoperative serum concentrations of
noradrenaline and cortisol. CONCLUSIONS: TIVA and VIMA induce similar hormonal
stress responses during anterior resection of the rectum. The increase in serum
adrenaline concentration during evaluation of the abdominal organs in the VIMA
group implies that the dose of sevoflurane should be escalated at this time
point.
PMID- 29952409
TI - Effectiveness of unilateral laparoscopic adrenalectomy in ACTH-independent
hypercortisolaemia and subclinical Cushing's syndrome - a retrospective study on
a large cohort.
AB - INTRODUCTION: To assess the effectiveness of early unilateral laparoscopic
adrenalectomy in ACTH-independent and subclinical hypercor-tisolaemia. MATERIAL
AND METHODS: We conducted a unicentric, retrospective study. Between 2010 and
2015, 356 laparoscopic adrenalectomies were performed in the Department of
General and Endocrine Surgery of the MUW. Hypercortisolaemia was found in 50
(14%) patients, while overt hypercortisolaemia was found in 31 patients. In the
hypercortisolaemia group, ACTH-dependent hypercortisolaemia was diagnosed in five
(10%) and ACTH-independent hypercortisolaemia in 25 patients (50%). One patient
with overt hypercortisolaemia had cancer of the adrenal cortex. The remaining 19
(38%) patients had subclinical Cushing's syndrome. For our study, we compared
patients with ACTH-independent hypercortisolaemia (n = 25) with those with
Cushing's syndrome (n = 19). Patients with ACTH-dependent hyper-cortisolaemia (n
= 5) and the patient with cancer of the adrenal cortex (n = 1) were excluded.
RESULTS: Patients from both groups (n = 44) underwent a unilateral
transperitoneal adrenalectomy. Good early outcomes were observed in 42 patients
(93.3%). In one patient, an additional laparoscopic surgery was necessary on
postoperative day 0 due to bleeding. In another patient, on day 22 post-surgery,
we found an abscess in the site of the excised adrenal gland, which was drained
under laparoscopic guid-ance. In three patients (6.8%) with substantial obesity,
temporary respiratory insufficiency of varying degrees occurred. We did not
observe any thromboembolic complications. All patients with overt
hypercortisolaemia and nine patients with subclinical hypercortisolaemia had
secondary adrenal insufficiency postoperatively. CONCLUSIONS: Transperitoneal
unilateral laparoscopic adrenalectomy is an efficient and safe treatment option
in patients with ACTH- -independent hypercortisolaemia, both overt and
subclinical.
PMID- 29952410
TI - Oxytocin treatment prevents marrow adiposity observed in alloxan-induced diabetic
rabbits using proton MR spectroscopy.
AB - INTRODUCTION: Oxytocin might be used therapeutically as an ally to rescue
osteopathy resulting from diabetes. However, the in vivo effects of oxytocin on
marrow adipogenesis in diabetes remain unknown. In this longitudinal study, we
aimed to investigate the protective ef-fects of oxytocin on diabetes-induced
marrow adiposity in rabbits using proton MR spectroscopy. MATERIAL AND METHODS:
Forty-five female New Zealand rabbits were randomly divided into controls,
diabetes, and diabetes treated with oxytocin (ip, 0.78 mg/kg) for six months.
Marrow fat fraction (FF) was determined by proton MR spectroscopy at baseline,
and at three and six months. Bone mineral density was measured by dual-energy X
ray absorptiometry. Serum biomarkers, glycolipid metabolism, and histological
analysis of marrow adipocytes were determined. RESULTS: Oxytocin treatment had
positive metabolic effects in diabetic rabbits, which was based on the changes in
glucose metabolism, insulin sensitivity, and lipid profiles. The diabetic rabbits
demonstrated dramatic marrow adiposity in a time-dependent manner; at three and
six months the FF percentage changes from baseline were 10.1% and 25.8%,
respectively (all P < 0.001). Moreover, oxytocin treatment significantly reversed
FF values and quantitative parameters of marrow adipocyte in diabetic rabbits to
levels of naive control rabbits. Oxytocin improved bone formation marker in
diabetic rabbits compared to the saline group. Also, treatment of diabetic
rabbits with oxytocin significantly mitigated bone deterioration when compared
with the saline-treated diabetic group (all P < 0.05). CONCLUSIONS: Oxytocin
appears to alleviate harmful effects of hyperglycaemia on marrow adiposity.
Proton MR spectroscopy may be a valuable tool, providing complementary
information on efficacy assessments.
PMID- 29952411
TI - Glutathione S-transferase (GST) polymorphism could be an early marker in the
development of polycystic ovary syndrome (PCOS) - an insight from non-obese and
non-insulin resistant adolescents.
AB - INTRODUCTION: It has been supposed that endocrine disturbances might be
responsible for polycystic ovary syndrome (PCOS)-associated oxida-tive stress,
with special emphasis on hyperandrogenism. Considering the potential relationship
between hyperandrogenism and increased free radical production, parameters of
oxidative stress were determined in non-obese normoinsulinemic adolescent girls
newly diagnosed with PCOS. MATERIALS AND METHODS: Nitrotyrosine, thiol group
concentrations, glutathione peroxidase, and superoxide dismutase activities were
determined under fasting conditions and during oral glucose tolerance test (OGTT)
in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the
homeostasis model (HOMA-IR), HOMA beta, insulinogenic index (IGI), Matsuda
insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases
(GSTs) polymorphisms were determined by PCR. RESULTS: Under fasting conditions,
no significant difference of oxidative stress parameters was found between PCOS
and controls. Acute hyperglycaemia during OGTT induced significant alteration in
parameters of oxidative protein damage in PCOS patients. Alteration in
nitrotyrosine concentrations correlated with testosterone, DHEAS,
androstenediones, FAI, and LH, while changes in thiol groups cor-related with
DHEAS. Significant inverse association was found between LH and ISI, as well as
AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had
significantly lower testosterone in comparison to ones with GSTM1-active
genotype. CONCLUSIONS: PCOS girls exhibited high free radical production together
with unchanged antioxidant enzymatic capacity, independently from obesity and
insulin resistance. Based on associations between oxidative stress parameters and
testosterone, DHEAS, and androsten-edione, it can be suggested that increased
free radical production, probably as a consequence of hyperandrogenaemia, is an
early event in the development of PCOS.
PMID- 29952412
TI - Total and high-molecular-weight adiponectin levels and prediction of insulin
resistance.
AB - INTRODUCTION: Adiponectin is a peptide secreted by adipocytes; its reduction is
associated with obesity-related disorders, including insulin resistance (IR). The
study analysed levels of total adiponectin and its high-molecular-weight (HMW)
oligomer in a group of metabolically healthy adults and in patients with type 2
diabetes mellitus (T2DM) to evaluate these levels as potential predictors of the
presence of IR. MATERIALS AND METHODS: The study comprised 269 metabolically
healthy adults and 300 patients with T2DM. Anthropometric and bio-chemical
indices were measured, including total and HMW adiponectin levels; the
Homeostatic Model Assessment of IR (HOMA-IR) index was calculated, and logistic
regression analysis was used to predict the presence of IR. RESULTS: In healthy
individuals, both total and HMW adiponectin levels were significantly higher than
in diabetic patients. Total and HMW adiponectin levels were moderately correlated
with the HOMA-IR index. Logistic regression analysis showed that increased levels
of both total adiponectin (odds ratio [OR] 0.598, 95% confidence interval [CI]
0.483-0.723) and the HMW form (OR 0.360, 95% CI 0.242-0.511) are protective
factors for the development of IR. The cut-off levels were 4.22 mg/L for total
adiponectin and 2.75 mg/L for HMW adiponectin. The results are valid for middle
aged European adults. CONCLUSIONS: Adiponectin levels below the indicated cut
offs may predict a potential risk for the development of IR.
PMID- 29952413
TI - Long-term risk of rosiglitazone on cardiovascular events - a systematic review
and meta-analysis.
AB - Rosiglitazone has been proposed as a treatment strategy for type 2 diabetes
mellitus (T2DM), and it could provide robust glucose-lowering capability with
risk of cardiovascular events. We thus performed a systematic review and meta
analysis of controlled trials to assess the effect of this treatment on glycaemic
control and cardiovascular events in patients with T2DM. We systematically search
PubMed, Embase, and the Cochrane Central Register of Controlled Trials comparing
rosiglitazone to other anti-diabetic treatments. These studies included
randomised controlled trials (RCTs), cohort studies, and case-control studies
that had treatment with at least six months of follow-up in patients with T2DM.
We aimed to evaluate the long-term effect on cardiovascular risk of rosiglitazone
compared with a basal insulin drug. The main outcomes included myocardial
infarction, heart failure, stroke, cardiovascular mortality, and all-cause
mortality. We included 11RCTs and four observational studies involving 20,079
individuals with T2DM allocated to rosiglitazone and a similar number to
comparison groups of which only five compared rosiglitazone with placebo and
collected data on cardiovascular outcomes. Among patients with T2DM,
rosiglitazone is associated with a significantly increased risk of heart failure,
with little increased risk of myocardial infarction, without a significantly
increased risk of stroke, cardiovascular mortality, and all-cause mortality
compared with placebo or active controls. Alternative methods to reduce the
uncertainty in long-term pragmatic evaluations, inclusion of rosiglitazone in
factorial trials, publication of cardiovascular outcome data from adverse event
reporting in trials of rosiglitazone and a cardiovascular endpoint trial of
rosiglitazone among people without diabetes.
PMID- 29952414
TI - Letter to Readers.
PMID- 29952415
TI - A study of the application of EZSCAN in pilots and in the general population.
AB - OBJECTIVE: This study aims to evaluate EZSCAN detection in pilots and the general
population, and determine the significance of EZSCAN detection in the
identification of a pilot's health. METHODS: A total of 87 cases of non-diabetic
Air Force pilots (pilot group) and 49 cases from the general population without
diabetes were collected. These two groups of subjects underwent EZSCAN detection,
as well as the detection of blood glucose, lipid and uric acid levels. RESULTS:
Subjects in the pilot group had the highest detection rate of no risk and the
lowest detection rate of high risk, while the general population had the highest
detection rate of high risk, followed by low risk. The difference in diabetic
risk between these two groups were statistically significant (P < 0.01). Various
indicators were compared according to different risk levels. In the no risk
group, age, BMI and the triglyceride of pilots were lower than in the general
population; and the difference was statistically significant (P < 0.05). In high
risk group, BMI and blood uric acid of pilots were lower than in the general
population; and the difference was statistically significant (P < 0.05).
CONCLUSIONS: BMI and blood uric acid are positively correlated to diabetic risk.
The EZSCAN detection system can be used for assessment of pilot's diabetic risk,
and has certain significance in a pilot's health identification.
PMID- 29952416
TI - MIF/CD74 axis is a target for metformin therapy in diabetic podocytopathy - real
world evidence.
AB - : Introduction:To observe the effects of metformin on urinary excretion of MIF,
CD74 and podocalyxin in type 2 diabetics and to explore its possible
renoprotective mechanisms. METHODS: 202 uncontrolled type 2 diabetics, who were
previously prescribed sulfonylurea monotherapy(n=100) or sulfonylurea in
combination with metformin (n=102) were enrolled in the study. The amount of
macrophage migration inhibitory factor(MIF) and CD74 in serum, urinary MIF to
creatine ratio(UMCR), urinary CD74 to creatine ratio(UCCR), urinary albumin to
creatine ratio(UACR) and urinary podocalyxin to creatine ratio (UPCR) were
determined. RESULTS: Metabolic parameters including fasting blood glucose,
postprandial 2 hours blood glucose, hemoglobin A1c, MIF and CD74 in serum were
comparable between the two groups. Moreover, metformin add-on therapy showed
significantly better efficacy in reducing UMCR, UCCR, UPCR and UACR in comparison
with those in sulfonylurea monotherapy group, respectively. UPCR had positive
correlation with UACR, UMCR and UCCR (r=0.73, r=0.69, r=0.62, P < 0.01),
respectively. CONCLUSIONS: Metformin could present its podocyte-protective
capacity in type 2 diabetics and the underlying mechanisms may be partly
attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory
cascade response. < p > < /p >.
PMID- 29952417
TI - Study on the relationship between the methylation of the MMP-9 gene promoter
region and diabetic nephropathy.
AB - OBJECTIVE: This study aims to explore the relationship between the methylation of
matrix metalloproteinase (MMP)-9 gene promoter region and diabetic nephropathy
(DN) through the detection of the methylation level of MMP-9 gene promoter region
in the peripheral blood of patients with DN in different periods and serum MMP-9
concentration. METHODS: The methylation level of the MMP-9 gene promoter region
was detected by methylation-specific polymerase chain reaction (MSP), and the
content of MMP-9 in serum was determined by enzyme-linked immunosorbent assay
(ELISA). RESULTS: Results of the statistical analysis revealed that serum MMP-9
protein expression levels gradually increased in patients in the simple diabetic
group, early diabetic nephropathy group and clinical diabetic nephropathy group,
compared with the control group; and the difference was statistically significant
(P < 0.05). Compared with the control group, the methylation levels of MMP-9 gene
promoter regions gradually decreased in patients in the simple diabetic group,
early diabetic nephropathy group, and clinical diabetic nephropathy group; and
the difference was statistically significant (P < 0.05). Furthermore, correlation
analysis results indicated that the demethylation levels of the MMP-9 gene
promoter region was positively correlated with serum protein levels, urinary
albumin to creatinine ratio (UACR), urea and creatinine; and was negatively
correlated with GFR. CONCLUSION: The demethylation of the MMP-9 gene promoter
region may be involved in the occurrence and development of diabetic nephropathy
by regulating the expression of MMP-9 protein in serum.
PMID- 29952418
TI - Elevated serum lipocalin 2 levels are associated with indexes of both glucose and
bone metabolism in type 2 diabetes mellitus.
AB - INTRODUCTION: The role of lipocalin 2 (LCN2) in type 2 diabetes mellitus (T2DM)
needs to be fully elucidated. Moreover, bone has been demonstrated to modulate
glucose metabolism via LCN2. We thus performed this study to investigate the
associations of LCN2 with indexes of glucose metabolism in T2DM. The associations
of LCN2 with bone metabolism were examined concurrently. MATERIAL AND METHODS:
Total 288 Chinese Han subjects entered in this study including 146 patients with
T2DM and 142 subjects with normal glucose tolerance. Insulin resistance was
assessed by HOMA-IR and.
PMID- 29952419
TI - Th17 and IL-17 exhibit higher levels in osteonecrosis of the femoral head and
have a positive correlation with severity of pain.
AB - OBJECTIVE: Synovitis associated with osteonecrosis of the femoral head (ONFH) is
responsible for several clinical symptoms. However, the mechanisms underlying
synovitis and the inflammatory environment remain unclear. This study analyzed
the proinflammatory mediation expression of IL-17 and Th17, which perform key
functions in regulating inflammatory processes in the inflamed synovium and
peripheral blood in ONFH. METHODS: Synovial fluid from the hips of 23 patients
and 5 controls was collected during surgery, and peripheral blood samples were
obtained from 34 patients and 9 controls. The expression of IL-17 in the synovium
was detected by immunohistochemistry, and the levels of Th17 and IL-17 in the
blood were measured by flow cytometry and ELISA. Pain assessment was performed
for all the patients and controls. RESULTS: An inflamed synovium was
characterized by increased leukocyte infiltration and IL-17 expression in
comparison with the control. Preoperative levels of Th17 and IL-17 were
significantly higher in the peripheral blood of the ONFH group than those in the
controls. The symptoms were also positively correlated with the Th17 levels of
the ONFH patients. CONCLUSION: Th17 cells were recruited to an inflamed synovium,
and inflammatory cytokine IL-17 was expressed at an increased level in the hip
synovium of ONFH patients, which possibly contributed to clinical syndrome
development. Overall, this study will help in identifying new therapeutic
strategies for ONFH, especially the targeting of IL-17 to decrease inflammation
and pain. < p > < /p >.
PMID- 29952420
TI - Thyroid hormones and obesity: a known but poorly understood relationship.
AB - Hormony tarczycy (thyroid hormones, TH) sa zaangazowane w wiele roznych procesow
biologicznych, wliczajac rozwoj ukladu nerwowego, regulacje metabolizmu
posredniego oraz zuzycie energii. Aktywnie uczestnicza w podstawowym zuzyciu
energii i termogenezie adaptacyjnej i z tego wzgledu moga miec wplyw na mase
ciala w przebiegu chorob tarczycy. Otylosc to niezakazna, przewlekla, zapalna
choroba metaboliczna, ktora implikuje dodatni bilans energetyczny. Tkanka
tluszczowa produkuje szereg hormonow i adipocytokin, takich jak leptyna, ktore
moga wplywac na stan tarczycy na roznych poziomach. Istnieja dowody na to, ze
dysfunkcja tarczycy moze predysponowac do otylosci i odwrotnie, istnieja dowody
sugerujace, ze otylosc powoduje zmiany dotyczace tarczycy. Celem tej pracy bylo
opisanie zwiazku miedzy ukladem tarczycy a otyloscia. Ponadto w pracy
zaprezentowano hipotetyczny model podkreslajacy znaczenie obwodowej dejodynacji
hormonow tarczycy i jego role w ustanowieniu dodatniego bilansu energetycznego.
Podsumowujac, mozemy stwierdzic, ze relacja miedzy ukladem tarczycy a otyloscia i
nadwaga jest zlozona i obejmuje wiele poziomow interakcji. Ponadto, poddajac
ocenie otylego pacjenta, powinno sie rozwazyc ocene funkcji tarczycy, aby uzyskac
lepsze i spersonalizowane efekty leczenia.
PMID- 29952421
TI - TeleNEN as a telemedicine model for neuroendocrine neoplasm management in case of
Meckel's diverticulum NET.
AB - A case of 25- years-old female with NET deriving from Meckel's diverticulum is
described. The patient had one year history of dermatological skin problems.
Ultrasound examination of abdomen performed because of arterial hypertension,
revealed multiple hepatic lesions, which was confirmed in contrast enhanced CT.
The typical contrast enhanced metastatic lesions in CT and elevated levels of
chromogranin A suggested NET of unknown origin. SRS with 99mTc-HYNICTOC was
perform for primary tumor localization, and revealed liver and paraaortic lymph
nodes metastases, but no sign of primary tumor location. As a next step for
primary tumor localization 68Ga-DOTATATE PET/CT was done, which revealed focus of
increased uptake in small intestine considered to be the primary tumor site. The
imaging and clinical history of patient was discussed on ENETS Tumor Board. Due
to location of primary tumor in the small intestine with no anatomical changes in
CT, laparotomy guided with gamma probe after 68Ga-DOTATATE injection was
performed. During surgery procedure, the primary tumor was hardly palpable in the
tip of Meckel's diverticulum, confirmed by gamma probe. After surgery, tandem
peptide receptor radionuclide therapy (PRRT) was started. Patient received 4
doses of 90Y/177Lu-DOTATATE with total activity of 360 mCi (13.32 GBq). The three
months follow up 68Ga-DOTATATE PET/CT had shown stable disease of patient. The
presented case showed importance role of multidisciplinary team cooperation in
patient management. Use of RGS is essential in cases like presented, when the
tumor cannot be localized only by surgical palpation.
PMID- 29952422
TI - Cystic pancreatic neuroendocrine tumours - a gastroenterologist's point of view.
AB - Cystic pancreatic tumors are detected with increasing frequency and remain a
clinical problem. Since they have different potential of malignancy the
management and decision making process is a hard task. Guidelines, concerning
pancreatic cystic tumors indicate the management with mucinous, serous cystic
pancreatic neoplasms and solid pseudopappilary tumor, while the management with
pancreatic cystic neuroendocrine tumors is not included into these standards.
This review tries to answer the question are the cystic pancreatic neuroendocrine
tumors different entity from solid tumors of neuroendocrine origin.The management
and differential diagnosis of these neoplasms with special focus on features on
imaging studies allowing preoperative diagnosis are discussed.
PMID- 29952423
TI - Serum sex hormones concentrations in young women in the early period after
successful kidney transplantation.
AB - BACKGROUND: Hormonal disorders are frequently present in hemodialysed patients
with chronic kidney disease (CKD). In women with CKD sex hormones abnormalities
may lead to irregular, often anovulatory cycles, sexual dysfunction and
infertility. Kidney transplantation done in young women tends to ameliorate most
of the aforementioned disorders and improve fertility. The aim of this study was
to assess the changes of serum sex hormones concentration in young women before,
and after the first 6 months after successful KTx Material and methods: Fourteen
chronic hemodialysis women with CKD undergoing kidney transplantation and 46
apparently healthy women in similar age (control group) were enrolled into the
study. In all women serum concentration of: FSH, LH, PRL and estradiol
determined. Measurements in the transplanted group were done four times:
immediately before surgery, in the 14th - and 30th - day and 6 months after the
transplantation. The results are presented as means and 95% CI. RESULTS: All of
the women that have finished the study presented an excellent function of the
transplanted kidney - mean serum creatinine concentration was 92.54 (74.85 -
110.23) umol/l. After successful KTx a significant decrease in the serum
concentrations of FSH and LH was observed. Decrease of serum PRL concentration
after KTx did not reach statistical significance in the multiple comparisons
analyses, but returned to the values observed in healthy controls. KTx did not
significantly influence serum estradiol concentration. CONCLUSIONS: Successful
kidney transplantation leads to the normalization of serum concentrations of
hormones linked to fertility disorders in women with chronic kidney disease. < p
> < /p >.
PMID- 29952424
TI - A follow-up study of patients with MEN syndromes - five case reports.
AB - THE AIM OF THE STUDY: Evaluation of the results of surgical treatment in patients
with hyperparathyroidism related to MEN syndrome MATERIALS AND METHODS: The group
of three women and two men aged between 17 and 72 years ( av. 38.6) with MEN-
related hyperparathyroidism within 419 patients were operated between 2010-2016.
MEN1 syndrome was diagnosed in four patients and MEN2 only once. Pre- and
postoperative results of PTH levels and serum calcium values were compared.
RESULTS: The mean preoperative serum PTH level was 215,56 pg/ml, whereas calcium
concentration was 1.40 mmol/l. Three Patients with MEN1 syndrome had three and
two thirds of parathyroid gland taken, and one had a single parathyroid gland
excised with biopsy of the rest glands performed. A patient with MEN2 syndrome
had one parathyroid gland excised. Postoperatively, we reported decreased
secretion of both PTH (a mean serum PTH concentration 6.72 pg/ml), and serum
calcium concentration 1.11 mmol/l. One patient (25%) with MEN 1 developed
recurrent hyperparathyroidism after five years from the surgery. The patient was
reoperated. The rest of the parathyroid gland was removed with an implantation
into separated muscle pockets in the anterior forearm muscles. CONCLUSIONS: 1.
MEN syndrome is a rare cause of primary hyperparathyroidism. 2. Subtotal
parathyroidectomy helps to bring back a normal calcium metabolism. 3. Recurrence
of hyperparathyroidism in patients with MEN syndrome requires total
parathyroidectomy with an autotransplantation into the anterior forearm muscles.
PMID- 29952425
TI - Sexual functioning and depressive symptoms in women with various types of
prediabetes - a pilot study.
AB - INTRODUCTION: No previous study has investigated sexual functioning in
prediabetic women. AIM: This study was aimed at investigating sexual function in
young women with various types of prediabetes. METHODS: The study included four
groups of women: women with isolated impaired fasting glucose (Group A; n=19),
isolated impaired glucose tolerance (Group B; n=18), presence of both impaired
fasting glucose and impaired glucose tolerance (Group C; n=18), as well as
matched healthy controls (Group D; n=19). All participants completed
questionnaires evaluating sexual function (Female Sexual Function Index - FSFI)
and the presence and severity of depressive symptoms (Beck Depression Inventory
Second Edition - BDI-II). RESULTS: The total FSFI and BDI-II scores were lower in
Group C than in the remaining groups of women, while the total FSFI score was
lower in Groups A and B than in Group D. Patients with both impaired fasting
glucose and impaired glucose tolerance had lower scores in all domains (sexual
desire, arousal, lubrication, orgasm, sexual satisfaction and dyspareunia).
Compared to Group D, Group A was characterized by lower domain scores for sexual
desire and sexual satisfaction, while Group B by lower domain scores for desire,
arousal and orgasm. In all groups of prediabetic women, the overall FSFI score
correlated negatively with the degree of insulin resistance and weakly with the
total BDI-II score. CONCLUSIONS: Impaired fasting glucose and impaired glucose
tolerance may disturb sexual functioning and induce depressive symptoms.
PMID- 29952426
TI - Expression of follicle stimulating hormone receptors in intra-tumoral vasculature
and in tumoral cells - the involvement in tumour progression and the perspectives
of application in cancer diagnosis and therapy.
AB - In normal conditions follicle stimulating hormone receptors (FSHR) are expressed
in zona granulosa cells of the ovary and Sertoli cells of the testis. However,
the ectopic expression of FSHR was recently discovered in intra-tumoral blood
vessels endothelia and/or in tumoral cells of many extra-gonadal human tumors
(particularly in endocrine tumours). The paper reviews the data concerning the
appearance of ectopic FSHR in particular human neoplasms. The possible
involvement of FSHR in tumor progression and the use of FSHR examination for
diagnostic purposes is also reviewed. Finally, the putative role of FSHR as a new
target in oncological therapy is also discussed.
PMID- 29952427
TI - Cystic lesions of the sellar-suprasellar region - diagnosis and treatment.
AB - The differentiation of cystic lesions located in the sellar-suprasellar region is
a significant problem in clinical practice because of the similarities in their
clinical, radiological, and even histopathological picture. Arriving at the right
diagnosis is vital for taking appropriate therapeutic decisions. The most
frequent clinical manifestation of lesions located in the sellar-suprasellar
region is headache. It often co-exists with symptoms of anterior pituitary gland
insufficiency or hyperprolactinaemia caused by compression of the pituitary
stalk. Diabetes insipidus, obe-sity, mental disorders, and circadian rhythm
disorders may be associated with lesions penetrating the suprasellar space. It is
extremely important to rule out the possible coexistence of pituitary
microadenoma and Rathke's cleft cyst, which became possible with the use of 11C
methionine positron emission tomography/computed tomography (C-MET PET/CT).
Reports from literature indicate that pituitary microadenoma may coexist with
Rathke's cleft cyst in 10% of patients. Cystic lesions of the sellar-suprasellar
region should also be differentiated from a cystic pituitary adenoma or abscess.
The first-choice therapy in symptomatic cystic lesions of the sellar-suprasellar
region is neurosurgery, which usually relieves headache and improves vision
impairment, while less frequently restores normal pituitary function. In
suprasellar lesions, neurosurgery may trig-ger or aggravate pre-existing symptoms
of damage to the hypothalamus. Patients undergoing neurosurgery for cystic
lesions located in the sellar-suprasellar region should be monitored for a few
years due to their high recurrence rate, potential malignant transformation of
these lesions, and possible adenoma development through metaplasia. The advent of
targeted therapy of the BRAF/MEK pathway is associated with new therapeutic
opportunities for patients with craniopharyngiomas.
PMID- 29952428
TI - Toosendanin, a natural product, inhibited TGF-beta1-induced epithelial
mesenchymal transition through ERK/Snail pathway.
AB - Epithelial-mesenchymal transition (EMT) plays important roles in the metastasis
of solid tumors. In this study, the effect of toosendanin (TSN), a natural
insecticide extracted from Melia toosendan Sieb et Zucc, on transforming growth
factor-beta1 (TGF-beta1)-induced EMT was investigated. EMT was induced by TGF
beta1 in A549 and H1975 lung cancer cells. The morphological alterations were
observed with a microscopy. The protein expression and localization of EMT
biomarkers were determined by Western blotting and immunofluorescence. The
migration, invasion, and adhesion were determined by wound-healing, transwell,
and adhesion assays. TGF-beta1 treatment induced spindle-shaped alterations of
cells, upregulation of N-cadherin, Vimentin, p-ERK1/2, and downregulation of E
cadherin. The abilities of migration, invasion, and adhesion were also enhanced.
These effects were significantly reversed by TSN at very low concentration (<10
nM). Furthermore, silence Snail significantly reversed TGF-beta1-induced EMT
biomarkers. In addition, TGF-beta1-induced phosphorylation of ERK1/2 without
affecting p38 mitogen-activated protein kinases and Jun N-terminal kinase.
PD98059 and U0126, inhibitors of ERK1/2, showed similar inhibitory effect to that
of TSN. In summary, TSN significantly inhibited TGF-beta1-induced EMT and
migration, invasion, and adhesion through ERK/Snail pathway in lung cancer cells.
This study provides novel anticancer effects and molecular mechanisms for TSN.
PMID- 29952429
TI - Effect of low androgen levels on IKca and SKca3 channels in rat penile corpus
cavernosum.
AB - We investigated whether low androgen levels affected erectile function by
regulating the expressions of intermediate-conductance Ca2+ -activated K+ channel
(IKca) and small-conductance Ca2+ -activated K+ channel 3 (SKca3) in corpus
cavernous of rats. Thirty-six healthy male SD rats were randomly divided into the
4-week control group, 4-week castration group, 4-week androgen replacement after
castration group, 8-week control group, 8-week castration group and 8-week
androgen replacement after castration group, respectively. The rats in the
androgen replacement groups were subcutaneously injected with testosterone (3
mg/kg) every other day after castration. After 4 and 8 weeks, maximum
intracavernous pressure/mean arterial pressure (ICPmax /MAP) was measured.
Expressions of IKca, SKca3, endothelial nitric oxide synthase (eNOS) and P-eNOS
in penile corpus cavernosum were detected. ICPmax /MAP decreased significantly in
the castration groups as compared to the control groups and the androgen
replacement groups (p < 0.01). mRNA expressions of IKca and SKca3 decreased
significantly in the castration groups as compared to the control groups and
androgen replacement groups (p < 0.01). Protein expressions of eNOS, P-eNOS, IKca
and SKca3 in the castration groups were significantly reduced as compared to the
control groups and androgen replacement groups (p < 0.01). Under low androgen
levels, ICPmax /MAP can be reduced by down-regulating the expressions of SKca3
and IKca, inhibiting P-eNOS/eNOS and reducing eNOS bioactivity.
PMID- 29952430
TI - Evaluation of dapoxetine treatment success in lifelong premature ejaculation
patients with penile sympathetic skin response.
AB - Hyperactivity of the sympathetic nervous system may play an important role in
primary premature ejaculation (PPE), and dapoxetine, a selective serotonin
reuptake inhibitor, plays a role in its treatment. We evaluated the success of
dapoxetine treatment in PPE patients with a penile sympathetic skin response
(PSSR). Of 63 patients who were admitted to our outpatient clinic between March
2017 and December 2017 with a complaint of premature ejaculation and diagnosed
with PPE, 56 completed treatment (minimum 12 tablets) with on-demand use 30 mg of
dapoxetine and returned for a follow-up appointment. Before and after treatment,
the International Index of Erectile Function (IIEF-5) and Arabic index PE (AIPE)
scores, intravaginal ejaculation latency time (IELT), testosterone values and
PSSR values were compared. The IELT and AIPE values increased significantly in
the 56 patients who were re-evaluated after dapoxetine treatment. No significant
changes were observed in testosterone levels and IIEF-5. In the PSSR measurement,
while the amplitude decreased, the latency was prolonged significantly. PSSR may
be an important determinant in the measurement of dapoxetine treatment success
for PPE patients, but additional studies are needed.
PMID- 29952431
TI - Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual
participant data review.
AB - BACKGROUND: This is an updated version of the original Cochrane Review published
in Issue 11, 2006 of the Cochrane Database of Systematic Reviews.Epilepsy is a
common neurological condition in which abnormal electrical discharges from the
brain cause recurrent unprovoked seizures. It is believed that with effective
drug treatment up to 70% of individuals with active epilepsy have the potential
to become seizure-free, and to go into long-term remission shortly after starting
drug therapy with a single antiepileptic drug (AED) in monotherapy.The correct
choice of first-line AED for individuals with newly diagnosed seizures is of
great importance. It is important that the choice of AEDs for an individual is
made using the highest quality evidence regarding the potential benefits and
harms of the various treatments.Carbamazepine or lamotrigine are recommended as
first-line treatments for new onset focal seizures and as a first- or second-line
treatment for generalised tonic-clonic seizures. Performing a synthesis of the
evidence from existing trials will increase the precision of the results for
outcomes relating to efficacy and tolerability and may assist in informing a
choice between the two drugs. OBJECTIVES: To review the time to treatment
failure, remission and first seizure with lamotrigine compared to carbamazepine
when used as monotherapy in people with focal onset seizures (simple or complex
focal and secondarily generalised) or generalised onset tonic-clonic seizures
(with or without other generalised seizure types). SEARCH METHODS: We conducted
the first searches for this review in 1997. For the most recent update, we
searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central
Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies
Online (CRSO), MEDLINE, Clinical Trials.gov and the WHO International Clinical
Trials Registry Platform on 26 February 2018, without language restrictions
SELECTION CRITERIA: Randomised controlled trials comparing monotherapy with
either carbamazepine or lamotrigine in children or adults with focal onset
seizures or generalised onset tonic-clonic seizures DATA COLLECTION AND ANALYSIS:
This was an individual participant data (IPD) review. Our primary outcome was
time to treatment failure and our secondary outcomes were time to first seizure
post randomisation, time to six-month, 12-month and 24-month remission, and
incidence of adverse events. We used Cox proportional hazards regression models
to obtain trial-specific estimates of hazard ratios (HRs) with 95% confidence
intervals (CIs), using the generic inverse variance method to obtain the overall
pooled HR and 95% CI. MAIN RESULTS: We included 14 trials in this review.
Individual participant data were available for 2572 participants out of 3787
eligible individuals from nine out of 14 trials: 68% of the potential data. For
remission outcomes, a HR of less than one indicated an advantage for
carbamazepine; and for first seizure and treatment failure outcomes, a HR of less
than one indicated an advantage for lamotrigine.The main overall results were:
time to treatment failure for any reason related to treatment (pooled HR adjusted
for seizure type: 0.71, 95% CI 0.62 to 0.82, moderate-quality evidence), time to
treatment failure due to adverse events (pooled HR adjusted for seizure type:
0.55 (95% CI 0.45 to 0.66, moderate-quality evidence), time to treatment failure
due to lack of efficacy (pooled HR for all participants: 1.03 (95% CI 0.75 to
1.41), moderate-quality evidence) showing a significant advantage for lamotrigine
compared to carbamazepine in terms of treatment failure for any reason related to
treatment and treatment failure due to adverse events, but no different between
drugs for treatment failure due to lack of efficacy.Time to first seizure (pooled
HR adjusted for seizure type: 1.26, 95% CI 1.12 to 1.41, high-quality evidence)
and time to six-month remission (pooled HR adjusted for seizure type: 0.86, 95%
CI 0.76 to 0.97, high-quality evidence), showed a significant advantage for
carbamazepine compared to lamotrigine for first seizure and six-month remission.
We found no difference between the drugs for time to 12-month remission (pooled
HR for all participants 0.91, 95% CI 0.77 to 1.07, high-quality evidence) or time
to 24-month remission (HR for all participants 1.00, 95% CI 0.80 to 1.25, high
quality evidence), however only two trials followed up participants for more than
one year so evidence is limited.The results of this review are applicable mainly
to individuals with focal onset seizures; 88% of included individuals experienced
seizures of this type at baseline. Up to 50% of the limited number of individuals
classified as experiencing generalised onset seizures at baseline may have had
their seizure type misclassified, therefore we recommend caution when
interpreting the results of this review for individuals with generalised onset
seizures.The most commonly reported adverse events for both of the drugs across
all of the included trials were dizziness, fatigue, gastrointestinal
disturbances, headache and skin problems. The rate of adverse events was similar
across the two drugs.The methodological quality of the included trials was
generally good, however there is some evidence that the design choice of masked
or open-label treatment may have influenced the treatment failure and withdrawal
rates of the trials. Hence, we judged the quality of the evidence for the primary
outcome of treatment failure to be moderate for individuals with focal onset
seizures and low for individuals with generalised onset seizures. For efficacy
outcomes (first seizure, remission), we judged the quality of evidence to be high
for individuals with focal onset seizures and moderate for individuals with
generalised onset seizures. AUTHORS' CONCLUSIONS: Moderate quality evidence
indicates that treatment failure for any reason related to treatment or due to
adverse events occurs significantly earlier on carbamazepine than lamotrigine,
but the results for time to first seizure suggested that carbamazepine may be
superior in terms of seizure control. The choice between these first-line
treatments must be made with careful consideration. We recommend that future
trials should be designed to the highest quality possible with consideration of
masking, choice of population, classification of seizure type, duration of follow
up, choice of outcomes and analysis, and presentation of results.
PMID- 29952432
TI - Global implications of the new WHO and UNICEF implementation guidance on the
revised Baby-Friendly Hospital Initiative.
AB - Although breastfeeding confers both short- and long-term benefits for children
and their mothers, breastfeeding practice remains suboptimal, globally. In
addition to barriers including misperceptions and inappropriate marketing of
breast milk substitutes, inadequate support for breastfeeding remains a challenge
in many settings. To improve access to appropriate health system support, the
World Health Organization (WHO) has reviewed the Baby-Friendly Hospital
Initiative (BFHI), which ensures provision of optimal clinical care and support
to mothers and their infants. This review has resulted in revision of the Ten
Steps to Successful Breastfeeding, which form the core standards of (BFHI). These
now consist of critical management procedures to support breastfeeding (Steps 1
and 2) and key clinical practices to support breastfeeding (Steps 3-10). In Step
1, there is now specific emphasis on compliance with the WHO Code of Marketing of
Breast-milk Substitutes and relevant World Health Assembly resolutions as well as
on internal monitoring. There are also significant position shifts like the
recommendation to "Counsel mothers on the use and risks of feeding bottles,
teats, and pacifiers," which is a departure from the earlier position of avoiding
reference to these technologies. These revisions require countries and states to
revise activities and tools for their local situation but without compromising
the standards.
PMID- 29952433
TI - Competency Based Medical Education.
PMID- 29952434
TI - Penicillin Allergy; Re-moulding Practice.
PMID- 29952435
TI - A Comparison of Perceived and Measured Paternal Weight and BMI, and Relationship
to Weight and BMI of his Children.
AB - INTRODUCTION: Nineteen percent of 9 years old Irish children are overweight;
seven percent are obese. Our aims were: to examine whether differences exist
between paternal self-reported and measured height, weight and BMI in a
population representative sample; and to explore paternal perceptions of their
own weight status. METHODS: Measures of height and weight for fathers and for
their children from the National Longitudinal Study of Children Growing Up in
Ireland were obtained using validated methods. RESULTS: Three quarters of fathers
(6,263 of 8,568 study children) with a mean age of 42 years (SD 5.04) responded.
The mean difference between self-reported and measured weight was -1.03kg
(SD=4.52), indicating that weight was underestimated. Obese fathers were more
likely to have an obese son (9.4% compared to 5.3% for the full cohort) and an
obese daughter (12.4% compared to 7.7%). DISCUSSION: These data suggest that
there is a strong relationship between fathers' weights and his childrens'
weights. A leading factor in the development of childhood obesity is parental
obesity. Targeting overweight and obesity in the child should occur
simultaneously with tackling overweight and obesity in the parents; in this
study, the fathers.
PMID- 29952436
TI - Magnetic Stent Removal in a Nurse Led Clinic; a Nine Month Experience.
AB - Ureteric stents are frequently inserted post endourological procedures. However,
subsequent endoscopic stent removal requires a second procedure for the patient
and the availability of necessary resources. Longer duration of indwelling stents
can lead to increased risk of symptoms and complications. The use of magnetic
stents removed with a magnetic retrieval device (BlackStar(c)), offers an
alternative which obviates the need for cystoscopy. We assessed the outcomes for
this novel method of stent removal in our institution. A retrospective analysis
was performed of all patients undergoing magnetic stent insertion and subsequent
removal in a nurse-led clinic over a nine-month period. Patients were followed up
with a prospective validated Ureteral Stent Symptoms Questionnaire (USSQ)3. A
cost analysis was also performed. In total, 59 patients were treated using
magnetic stents. The complication rate was low (6.7%). The median duration of
indwelling stent was 5.8 days (range 1-11 days). Patients reported haematuria and
lower urinary tract symptoms but >90% experienced no functional impairment with
minimal days of employment lost (mean 0.75 days). All patients reported
satisfaction with nurse-led stent removal and 97% were happy to have stents
removed via this method in the future. The total financial savings were estimated
at ?47,790 over this period. Nurse-led removal of magnetic stents is safe and
well tolerated by patients and enables expedient stent removal. It also provides
a significant cost benefit and frees up valuable endoscopic resources.
PMID- 29952437
TI - Point Prevalence of Adult Intestinal Failure in Republic Of Ireland.
AB - Parenteral Nutrition (PN) is a life-saving treatment used for patients with
Intestinal Failure (IF). PN is complex and demands highly specialised care to
avoid serious complications in the home setting. All tertiary centres in the
Republic of Ireland (ROI) were contacted to assess the prevalence of IF requiring
PN and complications, over a one year period. Sixty-seven patients were treated
across 15 centres: a period prevalence of 14.6 and 9.6 patients per million for
long-term PN and home PN respectively. Three-quarters of patients experienced at
least one major complication with 18% mortality rate over the study period. There
were 2.86 admissions per HPN patient, each lasting mean 13.4 days. One-third
experienced catheter-related infections. There was a reduced length of stay
during emergency re-admissions in high volume centres (mean 31 v 43 days,
p=0.17). The establishment of a National Centre for IF/HPN in ROI is integral to
reducing PN-associated complications.
PMID- 29952439
TI - Physical activity levels and perceived barriers to exercise participation in
Irish General Practitioners and General Practice trainees.
AB - Physical activity is a pillar stone of health promotion and primary care is
perfectly poised to disseminate this message. Primary care however, often fails
in this regard, missing an opportunity to promote a simple intervention that is
effective, free and easily accessible. This study aimed to determine physical
activity levels in Irish General Practitioners and General Practice Trainees in
addition to describing the barriers to exercise that exist amongst this cohort.
This cross-sectional study of Irish General Practice trainers and trainees
captured a categorical record of physical activity as well as a qualitative
measure of the perceived barriers to exercise. Only 49% (n=107) of those studied
engaged in health enhancing physical activity while 20% (n=44) were completely
inactive. Sixty percent (n=131) demonstrated excessively sedentary behaviour. The
greatest barriers to exercise were time expenditure and exhaustion. General
practitioners and trainees are more likely to engage with promoting physical
activity as a health intervention if its benefits are clearly demonstrable in
their own lives. This established trend of inactivity needs to be reversed if
physicians wish to realise significant health benefits in their own lives and
achieve substantial change in the health behaviours of their patients.
PMID- 29952438
TI - Outcomes of a Community-Based Paediatric Weight Management Programme in an Irish
Midlands Setting.
AB - Ongoing investigation is needed into feasible approaches which reduce excess
weight in childhood. This study aimed to assess the effectiveness of an adapted
version of the Scottish Childhood Overweight Treatment Trial (SCOTT) in an Irish
primary care setting. Families were offered monthly dietitian-led sessions for
six months. These sessions targeted dietary habits, family meals, screen time and
exercise. Of the 95 children (mean age 7.6 years) referred, 90.5% (n86) were
obese and 9.5% (n9) were overweight. Fifty-one (53.7%) families opted into the
programme from referral, and 18 completed the programme (64.7% attrition).
Statistically significant reductions in body mass index (BMI) were observed
between sessions one and six (25.7+/-4.2kg/m2 and 25.3+/-4.8kg/m2, respectively,
p<0.01). BMI z-score modestly decreased by 0.2 (p=0.01). Despite these
reductions, issues with programme referral, attrition and long-term effectiveness
were evident. Further investigation into strategies which reduce paediatric
overweight is warranted.
PMID- 29952440
TI - Kawasaki Disease - A Review of Treatment and Outcomes in an Irish Paediatric
Cohort 2010-14.
AB - Diagnosis of Kawasaki Disease (KD) can be challenging due to lack of a diagnostic
test, and some children present with 'incomplete' KD when not all diagnostic
criteria are met. Treatment with intravenous immunoglobulin (IVIG) and aspirin
reduces the risk of coronary artery complications. There is sub-group of patients
who are resistant to IVIG/aspirin therapy and are at increased risk of
complications. Recent evidence suggests that additional treatment of this high
risk group with corticosteroids is beneficial in reducing this risk. We examine
the treatment and coronary artery outcomes, by retrospective review of medical
records, of a cohort of 32 paediatric patients with KD admitted to a single Irish
tertiary centre from January 2010-December 2014. Twenty-eight percent of patients
(9/32) had an incomplete diagnosis of KD; these patients received IVIG later
compared to those with a complete KD diagnosis. 15/32 (47%) had abnormal
echocardiogram findings in the acute phase, 8/32 (25%) had echocardiogram
abnormalities at 6-week follow-up, and 4/32 (12.5%) had persisting abnormalities.
This study highlights the potential for adverse outcome in KD, the difficulty in
diagnosis in 'incomplete' cases, and the need to identify children at higher risk
for adverse outcome where adjunctive therapies would be most beneficial.
PMID- 29952441
TI - The Prevalence of Severe Sepsis or Septic Shock in an Irish Emergency Department.
AB - Severe sepsis and septic shock are among the leading causes of death globally.
Despite the central role the emergency department (ED) plays in the early
identification of patients presenting to hospital with sepsis, the prevalence of
severe sepsis and septic shock in the Irish ED setting has not been described.
The primary aim of this study was to measure the prevalence of severe sepsis or
septic shock in an Irish adult ED setting. The clinical records of patients
presenting to the ED over a four-week period were retrospectively reviewed to
determine if they met the current Health Service Executive (HSE) criteria for
severe sepsis or septic shock. Overall, 3,585 adult patients attended the ED
during the study period, with 42 patients meeting the criteria for severe sepsis
or septic shock. The ED prevalence of severe sepsis or septic shock was 11.7
patients (95% CI 8.1 - 15.4%) per 1000 ED attendances.
PMID- 29952442
TI - Low Yield of Positive Cerebrospinal Fluid (CSF) Culture and Bacterial PCR Tests
In Paediatric Patients With A Normal CSF White Cell Count.
AB - The aim was to review paediatric patients who had a positive cerebrospinal fluid
culture or bacterial PCR test, yet had a normal CSF white cell count for age.
Patients were included if they had a CSF sample sent for culture (between 2005
and 2015) or bacterial PCR (2010-2015), however neurosurgical and neurology
patients were excluded. Of the 2,482 patients reviewed, there were 101 patients
with laboratory-confirmed bacterial meningitis included, of which 27 were
positive by culture and PCR, 26 by culture alone and 48 were positive by PCR
only. Eighteen (18%) of these patients had CSF white cell counts within normal
range. Only one case with a normal CSF white cell count, where the lumbar
puncture was done after six days of antibiotics, was deemed to be clinically
significant. Bacterial PCR should not be routinely requested in patients with a
normal CSF white cell count, unless their blood culture is positive or unless
clinically indicated based on the assessment of a senior paediatrician.
PMID- 29952443
TI - DVD Versus Physiotherapist-Led Inhaler Education: A Randomised Controlled Trial.
AB - Correct technique with inhalers is vital for therapeutic effect. Efficacy of DVD
inhaler instruction was investigated. Secondary aims were to examine feasibility
of an inhaler technique outcome measure, and to compare knowledge and self
efficacy after DVD or individual education. This was a randomised controlled
trial conducted in a regional hospital paediatric ward, involving new or existing
paediatric inhaler users. Inhaler technique was assessed pre-education in
existing inhaler users. Participants were then randomised to message equivalent
education by DVD or individually with a physiotherapist. Inhaler technique, self
efficacy and knowledge were assessed immediately post- and three months after
education. Twenty one participants received DVD or individual education. There
were no significant differences between groups for technique, self-efficacy or
knowledge at any time. The outcome measure was feasible for use in a research
study. DVD education was equivalent to individual instruction to teach parents
how to use inhalers with their child.
PMID- 29952444
TI - A Borderline Ovarian Tumour in a Patient with Classic Bladder Exstrophy; a Case
Report.
AB - A 37-year-old Romanian lady presented with a large pelvic mass, urosepsis and
deteriorating renal function. She had undergone separation from her conjoined
twin. Imaging revealed grossly abnormal anatomy and a suspicious pelvic mass.
Examination was consistent with classic bladder exstrophy. Postoperative
histology showed borderline ovarian tumour (BTO).
PMID- 29952445
TI - Portal Hypertensive Colopathy with Pelvic Varices presenting as Severe Lower GI
Bleed treated with TIPSS.
AB - We present the case of a 71-year-old lady with a background of significant
alcohol intake who presented with frank lower gastrointestinal (GI) bleeding,
lower abdominal pain and haemoglobin 6.3g/dL. CT abdominal angiogram showed right
sided colonic thickening, atrophic liver and enlarged superior mesenteric vein
(SMV) and right-sided pelvic varix. This lead to a diagnosis of portal
hypertensive colopathy secondary to alcoholic liver cirrhosis. The patient failed
conservative management and underwent a Transjugular Intrahepatic Portosystemic
Shunt (TIPSS) procedure. This lead to an immediate resolution of her lower-GI
bleeding. Repeat CT at three weeks showed a decompressed SMV and resolution of
the right-sided pelvic varix. The patient was discharged after three months
following optimization of medical condition and social circumstances.
PMID- 29952446
TI - The Prevalence of Respiratory Symptoms in Irish Dairy Farmers.
AB - Work-related respiratory disease is a significant risk in the farming community.
We assessed respiratory symptoms using a validated work-related respiratory
questionnaire in 126 dairy farmers (19-75 years; 91.3% male). The prevalence of
cough symptoms was 34.4%. Thirty-seven farmers (29.4%) complained of upper airway
symptoms while forty (31.7%) complained of eye problems. Cumulated symptoms
scores did not indicate higher than normal rates of chronic lung disease. Only 10
farmers (7.9%) were taking medication for lung conditions. Only 7 (5.6%) were
current smokers. The rate of respiratory symptoms did not relate to the herd size
or the method of animal feeding used by the farmers. The incidence of respiratory
symptoms remains high among Irish dairy farmers. While the exact reason for this
is unknown it may be related to continuing work- related dust exposure.
PMID- 29952448
TI - A Paws for Thought: Paediatric Burn.
PMID- 29952447
TI - Identifying factors that influence the '6-hour target' in the Emergency
Department by applying Regression Analysis.
AB - AIM: To determine factors within the Emergency Department (ED) that have maximum
influence on the '6-hour target'. METHODS: Regression Analysis methodology
employed to analyse the influence of 9 ED variables on the '6-hour target'
compliance. RESULTS: The number of patients waiting to be seen an ED physician at
8pm exerts maximum influence on the '6-hour target' (r = -0.581, p<0.05).
CONCLUSION: The '6-hour target' compliance rises with lesser number of patients
waiting to be seen by an ED physician at 8pm. Also, the '6-hour target'
compliance rises by increasing the number of ED Registrar working hours and the
number of ED SHO working hours per day.
PMID- 29952449
TI - Follow Up Chest Radiography In Paediatric Pneumonia: Is It Avoidable?
PMID- 29952450
TI - SCN1A Variant and Cannabidiol Use.
PMID- 29952451
TI - Pioneer of Chinese Ophthalmology--130th Anniversary of Beijing Tongren Hospital.
AB - Much has been achieved in clinical and scientific research in the past 130 years
by Beijing Tongren Hospital, which has evolved from an eye clinic to a
comprehensive hospital with an ophthalmology department known as one of the best
in China. This article presents the most historic moments and events in the
development of a hospital with the largest eye care service volume. In addition,
given the leading position of Tongren, the development of ophthalmology in
Tongren is also the epitome of the development of modern ophthalmology in China.
Beijing Institute of Ophthalmology (BIO) was established in 1959 as an affiliated
institution under Tongren, aiming at carrying out applied science and basic
science research, and directors of BIO have thus far served 4 terms as president
of the Chinese Ophthalmological Society. In 2002, Beijing Tongren Eye Center
(hereafter referred to as the Eye Center) was established to combine all the
ophthalmic resources within Tongren. In 2017, the Eye Center alone had a surgical
volume of 78,223, with surgeries for cataract, refractive errors, fundus,
glaucoma, and corneal disease being the 5 most common, and 902,409 outpatient
visits. Equipped with the leading experts and equipment, Tongren is dedicated to
the battle against major eye diseases by carrying out large population-based
epidemiological surveys and basic science research on pathogenesis and effective
treatments, thereby making contributions to the development of the science of
ophthalmology along with the delivery of eye care services in China and beyond.
PMID- 29952452
TI - Special sample types: CSF.
PMID- 29952453
TI - Efficacy of a Single Intra-Articular Injection of 2% Sodium Hyaluronate Plus 0.5%
Mannitol in Patients with Symptomatic Osteoarthritis of the Knee: A Preliminary
Report.
AB - Background: Intra-articular injection of hyaluronic acid is widely used as a
treatment for osteoarthritis of the knee. The recommended dosing regimens have
generally ranged from 3 to 5 injections. Objective: To assess efficacy and safety
of a single intra-articular injection of 2% sodium hyaluronate plus 0.5% mannitol
in patients with symptomatic osteoarthritis of the knee. Material and Method:
Twenty patients between 40-70 years of age with osteoarthritis of the knee
(Kellgren-Lawrence grade II or III) were included in the study. After a 2-week
NSAIDs washout period, ten patients in the intervention group received a single
intra-articular 2 ml dose of the combination of 2% sodium hyaluronate and 0.5%
mannitol and ten patients in the control group received no injection. No other
pain-killer medication was allowed during the study except diclofenac as rescue
pain medication in both groups. The efficacy parameters were the WOMAC Index and
diclofenac consumption. All adverse events were recorded. Results: Patients who
received a single intra-articular injection of 2% sodium hyaluronate plus 0.5%
mannitol had a significant improvement from baseline in all WOMAC subscales over
24 weeks (p<0.001). Pain, stiffness, and physical function subscales were
significantly lower in the intervention group than in the control group until
Week 20, 12, and 16, respectively (p<0.05). Patients who received sodium
hyaluronate also required significantly lower amounts of diclofenac (p<0.05). No
serious adverse event related to the intervention was reported. Conclusion:
Symptomatic OA knee patients who received a single intra-articular injection of
2% sodium hyaluronate plus 0.5% mannitol had better outcomes over the 24-week
follow-up period than control group patients who received no injection
intervention.
PMID- 29952454
TI - Location of the Neurovascular Bundle of the Knee during Flexed and Extended
Position: An MRI Study.
AB - Background: The popliteal vessels and nerve are the structures most at risk
during surgery of the posterior knee compartment. Common procedures that could
interfere with or otherwise affect these structures include synovectomy, meniscal
repair, proximal tibial osteotomy, knee replacement and fixation around the knee
joint. Magnetic resonance imaging (MRI) can be used to locate the neurovascular
structures from the posterior bony landmark. MRI imaging is routinely studied in
the extended knee, but surgery of the posterior knee compartment is most often
performed with the knee in a flexed position. Objective: The aim of this study
was to investigate the location of the posterior neurovascular bundle relative to
the posterior aspect of the femur, tibia, and posterior cruciate ligament during
fully extended knee position and 90-degree flexed knee position using MRI.
Material and Method: MRI images of 26 knees were obtained from 25 patients. Ten
left knees, 14 right knees, and 1 bilateral knees were obtained from 18 males and
7 females. Axial plane and sagittal plane studies were used to measure the
shortest distance of the popliteal artery, popliteal vein, and tibial nerve to
the posterior bony aspect of the knee and the posterior cruciate ligament using a
digital ruler tool from the PACS X-ray system. Measurement was performed at joint
line level, 1 cm above joint line level, and 1 cm below joint line level in the
fully extended knee position and in the 90-degree flexed knee position. At the
joint line level, the mediolateral distance of the popliteal artery, popliteal
vein, and tibial nerve to the posterior cruciate ligament were also measured.
Results: At 1 cm above joint line level, mean anteroposterior (AP) distance from
the distal femoral condyle to the popliteal artery, popliteal vein, and tibial
nerve was 1.83+3.35 mm, 6.44+4.55 mm and 10.29+4.41 mm for full knee extension,
and 15.60+5.01 mm, 20.63+4.62 mm and 26.24+7.70 mm for 90-degree knee flexion,
respectively (p<0.001). At joint line level, mean AP distance from the posterior
tibial cortex to the popliteal artery, popliteal vein, and tibial nerve was
5.43+3.22 mm, 8.75+3.72 mm and 13.10+4.15 mm for full knee extension, and
11.64+5.48 mm, 17.59+6.53 mm and 21.52+10.67 mm for 90-degree knee flexion,
respectively (p<0.001). At 1 cm below joint line level, mean AP distance from the
posterior tibial cortex to the popliteal artery, popliteal vein, and tibial nerve
was 1.98+1.95 mm, 4.26+2.74 mm and 8.66+3.85 mm for full knee extension, and
6.91+2.86 mm, 12.34+5.23 mm and 16.58+9.22 mm for 90-degree knee flexion,
respectively (p<0.001). At joint line level, mean distance from the
posterolateral border of the PCL to the popliteal artery, popliteal vein, and
tibial nerve was 11.12+2.62 mm, 11.30+4.05 mm and 15.14+5.05 mm for full knee
extension, and 19.89+5.67 mm, 23.87+6.96 mm and 29.41+10.72 mm for 90-degree knee
flexion, respectively (p<0.001). Conclusion: During 90-degree knee flexion, the
neurovascular structures move posterolaterally, as compared to fully extended
knee position at joint line level and 1 cm above and below joint line level. To
prevent neurovascular injury during surgery, surgeons should avoid or be cautious
during blind penetration of the midline joint capsule and 90 degree flexed knee
position increases the distance of the neurovascular bundle away from the
posterior bony aspect.
PMID- 29952455
TI - Plate Fixation Technique for Reducing Osteoarticular Allograft Fracture: A
Preliminary Report.
AB - Background: Osteoarticular allograft is now commonly used as a reconstructive
biomaterial to replace bone defect following removal of aggressive bone tumors
and for revision of failed arthroplasty. Good long-term clinical result of
allograft replacement has been demonstrated. However, the rate of complications
is high, including deep infection, allograft fracture, delayed union or non
union, and joint instability. Prevalence of allograft fracture ranges from 12-54
percent. Many studies recommend avoiding plate and screw fixation, or they advise
the use of a modified screw fixation technique that minimizes the number of
screws and changes screw alignment. Objective: The objective of this study was to
compare the efficacy of the conventional technique with a new method of plate and
screw fixation in osteochondral allograft following removal of aggressive bone
tumors. Material and Method: From September 1988 to February 2015, 52 patients
with primary aggressive benign or malignant bone tumor underwent massive bone
allograft reconstruction. There were 25 males and 27 females with a mean age of
27-years. Giant cell tumor and osteosarcoma comprised most of the diagnoses.
Thirty-five of the tumors were located around the knee. Average length of
allograft was 12.9 cm. Twenty-nine patients were reconstructed using standard
technique and 23 patients were fixed using only one dynamic compression plate
with limited and 15-degree divergent-angle screw fixation at the allograft.
Results: Mean follow-up time in the group treated by conventional fixation was
84.5 months. There were 13 fractures (44.8%) in the conventional fixation group,
with a median time to graft fracture of 4.9 months. The 23 patients with new
technique fixation were followed-up for a mean duration of 60.5 months. Six
fractures (26.1%) occurred in this group, with a median time to graft fracture of
10.40 months. Differences between groups for incidence of allograft fracture and
median time to fracture were not statistically significant (p = 0.163 and p =
0.244, respectively). Most patients with allograft fracture were treated
surgically using autogenous bone grafting and revision of internal fixation.
Conclusion: The new method of osteochondral allograft fixation using single
plate, fewer screws, and divergent screw fixation yielded a lower fracture rate
and a longer median time to fracture than the conventional method; however the
differences between groups did not achieve statistical significance. The results
of this preliminary study should be confirmed in a larger group of allografts
over a longer follow-up period.
PMID- 29952456
TI - Emerging strategies for optimizing clinical chemistry performance. Performance
partnerships are playing an increasingly important role.
PMID- 29952457
TI - Prevalence of Radiographic Osteoarthritis and Structural Abnormalities of the Hip
in Patients with Contralateral Hip Fractures.
AB - Background: The prevalence of osteoarthritis (OA) of the hip varies considerably
among different races and ethnicities. Some bony abnormalities associated with
the development of hip OA. Objective: To determine the prevalence of radiographic
OA and structural abnormalities of the hip in patients with contralateral hip
fractures. Material and Method: Pelvic AP radiographs of patients more than 60
years of age who had contralateral hip fractures were reviewed. Radiographic
diagnosis of hip OA was determined by minimum joint space width <2 mm. Kellgren
Lawrence classification was also used for evaluation. Structural abnormalities of
the acetabulum and proximal femur regarding femoroacetabular impingement were
also assessed. Results: Plain radiographs of 152 patients with an average age of
77.4 years were included. One hundred and thirteenpatients (74.3%) were female.
Prevalence of radiographic OA of the hip (minimum joint space width <2 mm) was
9.9%. In addition, 9.2% of hips were Kellgren-Lawrence grade 2 or higher. Pistol
grip deformity was found in 6 patients and all were male. Five patients (3.3%)
had cross-over sign. No protrusio acetabuli was detected. Coxaprofunda was
identified in 72 patients (47.4%). Average center-edgeangle was 37.1+6.2 degrees
in hips with coxaprofunda, and 35.9+5.3 degrees in hips without coxaprofunda (p =
0.180). Conclusion: Prevalence of radiographic OA of the hip in patients with
contralateral hip fractures was 9.9%. Coxaprofunda was a common radiographic
finding.
PMID- 29952459
TI - Innovations in the management of the diabetic foot.
PMID- 29952458
TI - Protein biomarker discovery. Researchers are bridging the gap between discovery
and validation for clinical use.
PMID- 29952461
TI - Keeping clinical lab errors to a minimum.
PMID- 29952460
TI - The Comparison between Computer-Assisted Hexapods and Ilizarov Apparatus in
Gradual Tibial Deformity Correction: A Preliminary Study.
AB - Background: The Hexagonal external fixator (Hexapods) is known to have the
ability to correct complex multi-planardeformities faster than the Ilizarov
apparatus. However, the difficulty of achieving deformity correction by Hexapods
seems to limit its popularity. Objective: This study aims to compare the
advantages and disadvantages of Hexapods and Ilizarov in the gradual correction
of complex tibial deformities. Material and Method: A retrospective review was
performed in patients with complex tibial deformities treated with Hexapods or
with Ilizarov apparatus from 2000 to 2014. Magnitude of deformity, length of time
in Hexapods or Ilizarov apparatus, Lengthening Index, and complications were
recorded. Statistical analysis was used to compare the two methods. Results: Six
patients were treated with Ilizarov apparatus and seven patients were treated
with Hexapods. Patients inHexapods group had more coronal plane angulation before
surgery than in the Ilizarov group with statistical significance (p = 0.02). The
differences of the sagittal and the axial plane angulations were not
statistically significant. The difference of leg length was also not
statistically significant. After completion of treatment, no statistical
significance of residual deformities was found between the two methods.
Lengthening Index had trends toward significance in Hexapods group (p = 0.051).
Conclusion: Computer-assisted Hexapods may reduce the Lengthening Index compared
to the conventional Ilizarov method. The hexapods device could be beneficial for
faster correction of complex deformity if the patients or family members
understand how to manipulate the apparatus.
PMID- 29952462
TI - The human side of lab automation. Here are some best practices to break down the
"silos".
PMID- 29952463
TI - The Necessity of Hip Lateral Radiograph for Operative Decision in Two Common Hip
Fractures.
AB - Background: Recent studies showed that single hip anterio-posterior (AP)
radiograph was adequate for diagnosis of most hip fractures (HF). However,
lateral hip radiograph might be necessary to understand the fracture
characteristics and to make better decision on surgical management. Material and
Method: 100 HF radiographs (50 femoral neck fractures [FNF] and 50
intertrochanteric fractures [ITF]) were consecutively reviewed by five observers.
The initial review used only single both hips AP radiograph. One month later,
both hips AP and lateral films were reviewed. The diagnosis and operative
decision were recorded, and then calculated. Results: The average rate of
changing treatment by the assessment of lateral radiographs was 5.0% for all HF,
2.8% for FNF, and 7.2% for ITF. There was no significant difference among those
rates between five observers (p<0.05 all). The Intraclass Correlation
Coefficients (ICCs) for interobserver agreement regarding the operative decision
using only single AP film were 0.787 (95% confidence interval [CI], 0.698 to
0.852) for all HF, 0.818 (95% CI, 0.699 to 0.893) for FNF, and 0.394 (95% CI,
0.130 to 0.606) for ITF. After using both AP and lateral film, the ICCs were
changed into 0.792 (95% CI, 0.705 to 0.856) for all HF, 0.795 (95% CI, 0.663 to
0.879) for FNF, and 0.552 (95% CI, 0.323 to 0.720) for ITF. Conclusion: Using
single both hips AP radiograph for operative decision is adequate and safe for
most hip fractures. However, some of intertrochanteric fractures may require
lateral radiograph for better operative decision.
PMID- 29952464
TI - Humanitarian endeavor brings rapid cancer diagnostics to sub-Saharan Africa and
Haiti.
PMID- 29952466
TI - [In process]
PMID- 29952465
TI - The Results of Lengthening in Congenital Posteromedial Angulation of Tibia.
AB - Background: Congenital posteromedial bowing of the tibia (PMBT) is a rare
deformity with limb length discrepancy (LLD) with or without significant angular
deformity. Some patients need only limb length equalization while many patients
require additional angular correction. Limb length equalization may be achieved
by either limb lengthening, epiphysiodesis or acute shortening of the long leg.
Limb lengthening is the preferred treatment option in PMBT patients with
significant angular deformity. Objective: The presented study is to evaluate the
results of lengthening with Ilizarov fixator in these patients. Material and
Method: PMBT patients treated with Ilizarov lengthening were retrospectively
reviewed. Progression ofangular deformity and LLD were assessed. Residual
deformity after Ilizarov lengthening and complications were also evaluated.
Results: Limb lengthening with Ilizarov external fixator was performed in 4 PMBT
patients. Mean age at surgery was 3.7years. Expected LLD (using multiplier
method) of tibia ranged from 5.1 to 9.9 cm. Younger patients had more angular
deformity than older patients. One patient had pin tract infection requiring
Ilizarov removal. Lengthening index varied from 1.2 to 2.1 month/centimeter. LLD
after the lengthening was -1.4 to 0.4 cm. Mean progression of LLD was 1.8
mm/year. Conclusion: Ilizarov lengthening for posteromedial angulation shown good
result with average residual LLD 0.4 to 1.4 cm which is not clinically
significant.
PMID- 29952468
TI - Reference Values of Different Height of Diaphragms in Chest Radiographs of
Newborns.
AB - Background: There are many causes affecting diaphragmatic height including normal
variation and pathology. Both elevation and depression of the diaphragm imply
various pathologies. In our knowledge, no previous study of newborn evaluated the
different height of diaphragms. Using adult's reference value in interpretation
of newborns' chest remains doubtful because of different imaging technique.
Objective: To assess diaphragmatic height and measure different height of
diaphragms in the chest radiographs of newborns. Material and Method: A
retrospective review of chest radiographs was performed on 100 newborns (age less
than 1 month) who were diagnosed of transient tachypnea of the newborn (TTNB)
that had respiratory distress and abnormalities in chest radiographs disappeared.
The diaphragmatic positions and different diaphragmatic height were evaluated in
relation to thoracic vertebra and posterior rib. Results: Right diaphragmatic
dome was positioned at 8.17+0.72 thoracic vertebral levels below the top of first
thoracic vertebra and 8.28+0.78 crossing rib levels. Left diaphragmatic dome was
positioned at 8.87+0.71 thoracic vertebral levels and 8.91+0.29 crossing rib
levels. The different height of diaphragms was 0.70+0.34 thoracic vertebral body
and 0.63+0.29 intercostal spaces. No newborn had the left diaphragmatic dome
higher than the right side. Conclusion: The different diaphragmatic height in
newborns is less than 1 intercostal space or 1 thoracic vertebral level.This
knowledge is useful for assessment of chest radiographs.
PMID- 29952469
TI - Peripheral artery disease: basic knowledge.
AB - Peripheral artery disease is characterized by a limited blood circulation caused
by stenosis or occlusion of peripheral arteries of the extremities. It is
considered as a marker-disease of an advance atherosclerosis. Comorbidity with
other manifestations of atherosclerosis like myocardial infarction or stroke is
high.
PMID- 29952470
TI - A rare case of multiple schwannomas originating from a single cauda equina root.
PMID- 29952471
TI - Surgical management of traumatic brain injury.
AB - Traumatic brain injury (TBI) remains a leading cause of mortality and disability
worldwide. Surgical intervention is one of the main pillars of TBI management.
The mainstay of treatment for substantial intracranial hematomas is surgical
evacuation. In addition, patients with TBI may have brain swelling and increased
intracranial pressure. If the latter is refractory to medical management,
surgical interventions can be helpful. In this review we seek to outline the
major tenets of the surgical management of TBI.
PMID- 29952473
TI - Predictors of the Functional Abilities in Individuals with Stroke after Home
Physical Therapy Program.
AB - Background: Community stroke rehabilitation has been reported to be beneficial.
Evidences of factors influencing the functional outcomes of home based treatment
were limited. Objective: To identify the predictors of the activities of daily
living (ADL) function of individuals with stroke after obtainingtreatment program
at home. Material and Method: Three hundred sixty five individuals with stroke
that participated in the home rehabilitation program were included in the present
study. The patients received six months of physical therapy treatment program at
home according to the results of evaluations. Personal characteristics and
clinical outcomes including Gasglow coma, Barthel index (BI), Postural Assessment
Scale for Stroke Patients (PASS), and Stroke Rehabilitation Assessment of
Movement (STREAM) were recorded. Results: At discharge, five variables were
identified as the predictors of Barthel index scores and explained 90.5%
ofvariances. The PASS maintaining position was the strongest predictors
contributing 86.0%. The STREAM, PASS changing position, Gasglow coma score and
age then added 4.5% of variances explanation of the BI score. Conclusion: The
ability to perform ADL in stroke patients was greatly explained by the ability to
maintain positions at the time of discharging from the rehabilitation program at
home. Other outcomes contributed in the different manners compared to the time of
starting rehabilitation program.
PMID- 29952472
TI - Peripheral artery disease: diagnosis
AB - Basic diagnostics includes inspection of the skin, palpation of leg and foot
pulses and determination of the ankle-brachial-index. The hemodynamic relevance
of the circulation problem is important for the therapeutic decision. For its
determination several noninvasive procedures are available. Treadmill test can
help to differentiate between vascular and other causes of walking limitation.
PMID- 29952474
TI - Peripheral artery disease: Introduction and conservative treatment.
AB - Therapeutic goals are reducing cardiovascular risk and and improving the
circulation in the leg. Therapeutic options are surgical and endovascular
procedures as well as conservative treatment. The main focus for patients with
intermittent claudication is to enhance quality of life. Patients with critical
ischemia however are threatened by the loss of an extremity. In these cases, a
conservative treatment is usually not sufficient and circulation must be quickly
ameliorated by an endovascular or surgical procedure.
PMID- 29952475
TI - Rate of Serum Valproate Concentration Monitoring in Patients with Bipolar
Disorder Type I at Srinagarind Hospital Outpatient Clinic.
AB - Objective: Determine in the out-patient setting the rate and the purpose of serum
valproate concentration monitoring during treatment with valproate, either single
valproate or valproate in combination with other psychotropics in patients with
bipolar disorder type I (BD-I), to determine the rate of recording valproate
associated adverse effects, the rate of the follow-up and the length (days) that
the patients were in the condition of full remission/recovery and symptomatic.
Material and Method: The present study was a retrospective descriptive study done
between January 1, 2007 and December 31, 2008. The data were from the medical
records of DSM-IV-TR BD-I out-patients at Srinagarind Hospital, Khon Kaen who
were treated either by single valproate or valproate in combination with other
drugs for at least six weeks long. The studied variable included the annual rate
and the reason that psychiatrist requested serum valproate concentration (SVC)
monitoring per patient, the annual rate that psychiatrist recorded the valproate
associated adverse effects, the annual rate that the patient returned to have a
follow-up visit, and the length (days) that the patient was in full
remission/recovery and symptomatic. Results: During the study period, of the 199
patients with BD-I, only 57 patients (28.6%) that were treated with valproate had
complete records. The SVC monitoring occurred 17 times from 13 patients (22.8%).
The mean SVC was 76.4 microgram/ml (SD = 31.8). The mean value +SD and range of
SVC during the remission/recovery period were 75.1+17.5 MUg/ml and 43.5-96.8
MUg/ml, which was not significantly different from the symptomatic period, which
was 77.1+39.9 MUg/ml and 0.7 to 124.9 MUg/ml. However, the oral dosage of
valproate during the remission/recovery period (944.7+275.4 mg/day, median 1,000
mg/day) was significantly higher than during the symptomatic period (699.0+592.5
mg/day, 1,000 mg/day) (t = 2.7, df = 104 and p = 0.009). Of all the SVC
monitoring, 58.8% occurred during the symptomatic period and most of the
monitoring was due to the emergence of adverse effects. The causes for requesting
the SVC determination were the emergence of adverse effects (29.4%), no reason
specified (29.4%), and to monitor the clinical response (11.8%). The rate of
valproate associated adverse effects recording was 1.1 times/person/year, which
was 18.6% of the average rate of follow-up visits (6.6 times/person/year). The
most frequent adverse effect was sedation. The treatment of BD-I by valproate or
in combination with other psychotropics resulted in the remission/recovery period
lasting 470.2 days (SD 256.8, median 517.0) while the symptomatic period lasted
176.1 days (SD 157.5, median 139.5). Conclusion: During treatment of BD-I, the
rate of serum valproate concentration monitoring was very few. However, when
determination was requested, the SVC was within the therapeutic range. In
addition, rate of recording of valproate associated adverse effects was very low
and the most frequent adverse effect was mild. The reason for monitoring the
clinical response was rarely found. Valproate seems to be easily administered.
The dosage can be adjusted using only clinical response and adverse effects.
Therefore, valproate was effective and safe in treatment of BD-I.
PMID- 29952476
TI - Peripheral artery disease: endovascular therapy.
AB - Endovascular therapy of peripheral artery disease is currently first-line
treatment for a lot of indications. This is based on positive outcomes of modern
treatment strategies employing drug-eluting balloons and drug-eluting stents.
PMID- 29952477
TI - A patient with peripheral artery disease.
AB - A 56 year old person presents with pain when walking. A peripheral artery disease
in the iliacic vessels is diagnosed. Endovascular therapy results in a
significant improvement. The following conservative treatment aims at reducing
the cardiovascular risk. Especially stopping smoking turns out to be hard to
achieve.
PMID- 29952478
TI - Preoperative and postoperative ultrasound assessment of stress urinary
incontinence.
AB - INTRODUCTION? The role of ultrasound imaging in urogynecology is not defined.
Significant developments in visualization techniques and interpretation of images
allowed to study structures of the lower genitourinary tract and pelvic floor.
EVIDENCE ACQUISITION? PubMed and Scopus database were searched for publications
on the following item: stress urinary incontinence, ultrasound, perineal
ultrasound and preoperative and postoperative assessment. EVIDENCE SYNTHESIS? The
role of ultrasound in urogynecology could be helpful in diagnosing of urinary
incontinence and urethral hypermobility, to document pelvic floor anatomy and to
assess anatomic and functional changes before and after surgery. CONCLUSIONS?
Ultrasound could be an important step during preoperative and post-operative
assessment of patients affected by stress urinary incontinence.
PMID- 29952480
TI - [In process].
PMID- 29952479
TI - L4-L5 Total Dislocation with Cauda equina Syndrome: A Case Report.
AB - Background: There are very few reports in the literature that describe total
anterolateral fracture dislocation of L4 and L5. To present a case report of L4
L5 total dislocation with major neurological deficit and open fracture of left
distal femur. Case Report: A 45-year-old Thai woman was transported to hospital
with severe trauma, low back pain, a shallow lacerated wound on her back, and
ecchymosis around waist and trunk. Closed reduction was initially performed and
followed with posterior decompression, fusion, and instrumentation with pedicular
screws and rod systems from L3-S1. Open reduction and internal fixation of distal
femur was then performed. Conclusion: At 1-year follow-up, the patient could
ambulate with left ankle-foot orthosis (AFO) using a walker.
PMID- 29952481
TI - Syphilis - an update.
AB - Syphilis is a chronic, multi-stage bacterial infection disease caused by the
spirochate Treponema pallidum subsp. pallidum. In the primary stage of the
disease, there is usually an ulcer formation (primary affection) in the
genitoanal region. During the secondary stage, numerous, mainly skin-related
disorders may appear. After a latency lasting up to several decades, a further
stage can develop, in which the skin, the heart or the nervous system
(neurosyphilis) is particularly affected. Applying an adequate antibacterial
treatment regime with benzylpenicillin derivatives, syphilis can be cured in most
cases at any stage of the disease. Exposure prophylaxis is most important in the
prevention of syphilis.
PMID- 29952482
TI - Working together to enhance medication safety: working group ,medication safety'
of the Aktionsbundnis Patientensicherheit e.V.
AB - For 12 years, the ,Aktionsbundnis Patientensicherheit e.V. (APS)' has been
developing tools for improving patient safety. Experts with different
professional backgrounds are working alongside patients and self-help
associations in different working groups to develop and publish problem-oriented
best-practice recommendations. Since its foundation in 2005, APS has published
more than 20 best-practice recommendations and is one of the most important
institutions for patient safety in Germany. In this article, the aims and
initiatives of one working group of the APS, i.e. the medication safety working
group, are presented. The standardized concept for the development of best
practice recommendations is illustrated by the example of the recommendations for
medication safety in hospitals.
PMID- 29952483
TI - Prevalence and incidence - what's the difference?
AB - Prevalence and incidence are measures to quantify the frequency of a certain
disease. For correct interpretation of data the calculation of correct
parameters, the right population under risk and the definition of cases have to
be considered.
PMID- 29952484
TI - [In process].
PMID- 29952485
TI - [In process].
PMID- 29952486
TI - [In process].
PMID- 29952487
TI - Correlation between Iodine Supplement in Pregnancy and Neonatal TSH Level.
AB - Objective: To evaluate the correlation of neonatal thyroid stimulating hormone
(TSH) between iodine supplemented and no-iodine supplemented pregnant women.
Material and Method: The present study was a prospective randomized controlled
trial (RCT) that was taken at ANC unit, labor ward, and neonatal unit at Siriraj
Hospital, Mahidol University, Bangkok, Thailand. Two hundred sixty six pregnant
women were recruited between June 15, 2015 and July 31, 2016. They were
randomized into two groups, iodine and no-iodine supplemented group. Results: No
statistical significant of demographic data, original habitant areas, and adverse
neonatal outcomes including preterm labor and low birthweight, of the pregnant
patient between these two groups. Only the median value of neonatal TSH level was
3.44 and 3.95 mIU/l in iodine and no-iodine supplemented group, respectively,
which was statistically significant different between the two groups (p-value
<0.05). However, there were no clinical difference between the two groups.
Conclusion: The present study presented that there was statistical significant
difference of the median value of neonatal TSH level between two groups of iodine
and no-iodine supplement pregnant women. Even if there was no clinically
significant difference and none of the newborn was diagnosed of hypothyroidism,
iodine supplementation in all pregnant women should be of concerned. A large
prospective study would benefit the iodine implementation of pregnant women in
Siriraj Hospital.
PMID- 29952488
TI - [In process].
PMID- 29952489
TI - [In process].
PMID- 29952490
TI - [In process].
PMID- 29952491
TI - [In process].
PMID- 29952492
TI - [In process].
PMID- 29952493
TI - [In process].
PMID- 29952494
TI - Cancer - an overview.
AB - Cancer is characterized by proliferation of cells that have managed to evade
central endogenous control mechanisms. Cancers are grouped according to their
organ or tissue of origin, but increasingly also based on molecular
characteristics of the respective cancer cells. Due to the rapid technological
advances of the last years, it is now possible to analyze the molecular makeup of
different cancer types in detail within short time periods. The accumulating
knowledge about development and progression of cancer can be used to develop more
precise diagnostics and more effective and/or less toxic cancer therapies. In the
long run, the goal is to offer to every cancer patient a therapeutic regimen that
is tailored to his individual disease and situation in an optimal way.
PMID- 29952495
TI - Breast cancer: basics, screening, diagnostics and treatment.
AB - Breast cancer is by far the most common malignancy in women. The median age is 64
years. Stage at diagnosis and biological features determine the prognosis.
Patients with early breast cancer, with locally advanced disease and with
locoregional relapse can be cured. Modern treatment is multimodal. It includes
surgery, radiation and drug therapy. Patients with metastatic disease are treated
with palliative intent. Aims are alleviation of symptoms and prolongation of
survival. Breast cancer specific mortality has continually decreased in the past
10 years. Five year survival rate is 87% in Germany. Patients with early breast
cancer have an even higher chance of cure.
PMID- 29952496
TI - Diagnostic Accuracy and Optimal Cutoff Value of Serum HE4 to Predict Ovarian
Cancer in Thai Women with Pelvic Masses.
AB - Background: Serum human epididymis protein 4 (HE4) is highly expressed in women
with ovarian cancers (OCs), but data about its clinical application of HE4 for
Thai women is limited. Objective: To evaluate the diagnostic accuracy and optimal
cutoff for HE4 in distinguishing benign lesions, borderline ovarian tumor (BOTs),
and OCs compared with CA125 in Thai women at Rajavithi Hospital. Material and
Method: The cross-sectional study was conducted in Thai women aged older than 18
years old with pelvic masses whom underwent elective surgery at Rajavithi
Hospital between 2012 and 2013. Preoperative serum HE4 and CA125 levels were
measured and pathologic specimens were reviewed. Results: Of the 518 participants
evaluated, 316 had benign lesions, 43 had BOTs, and 159 had OCs. Between non
cancers and OCs, area under receiver operating characteristic curve (ROC-AUC) for
HE4 hardly differed from CA125 (0.85 vs. 0.83, p = 0.402) but was significantly
lower in postmenopausal women (0.79 vs. 0.86, p = 0.049). The optimal cutoff
value of HE4 was 72 pM/L for all menopausal status. Lower HE4 was seen in 30.8%
of mucinous carcinoma and 31.7% of clear cell carcinoma. The HE4 ROC-AUC was
significantly higher than CA125 ROC-AUC in distinguishing benign diseases and
BOTs (0.71 vs. 0.53, p<0.001), HE4 in 70% of BOTs was 51 to 95 pM/L. Conclusion:
Although the 72 pM/L cutoff for HE4 was appropriate in distinguishing between non
cancers and OCs for both pre- and postmenopausal women, the limitation for
postmenopausal women, mucinous carcinomas, and clear cell carcinomas require to
be complemented with CA125.
PMID- 29952498
TI - [In process].
PMID- 29952497
TI - Supportive care of cancer patients illustrated by case examples.
AB - Despite important medical progress, supportive care still plays a central role in
cancer therapy. Severe tumour- and therapy-related symptoms not only affect the
patient's quality of life, but can also compromise the therapy outcome.
Therefore, an effective supportive care is crucial in cancer therapy. In
community pharmacies as well as in hospital pharmacies pharmacists contribute
essentially to supportive care through qualified advice and individual support.
Case examples within the field of cytotoxic and targeted therapy provide insight
into the management of nausea and vomiting, diarrhoea, and papulopustular rash.
PMID- 29952499
TI - Music Listening to Decrease Pain during Second Trimester Genetic Amniocentesis: A
Randomized Trial.
AB - Objective: To evaluate whether music listening decreased pain perception during
second trimester genetic amniocentesis. Material and Method: We conducted a
prospective randomized study to compare the pain perception using a visual
analogue scale (VAS), pain rating, future decision to repeat the procedure, and
pain perception compared to a venipuncture before and after the second trimester
genetic amniocentesis between groups of pregnant women who underwent
amniocentesis with and without music listening. Results: Three hundred thirty two
pregnant women were enrolled; 161 listened and 171 did not listen to the music.
The pre-procedure anxiety, the anticipated pain, post-procedure pain/ anxiety
median VAS scores, pain rating, future decision and level of pain compare to a
venipuncture in the music-listening and non-music-listening groups did not show
statistically significant difference. The pre-procedure anxiety median VAS scores
were 1.3 and 0.5 in the music-listening and non-musiclistening groups,
respectively and the anticipated pain median VAS scores were 4.8 and 4.5 in the
music-listening and non-music-listening groups, respectively. The post-procedure
median VAS pain/anxiety scores were 2.7 and 2.5 in the music-listening and non
music-listening groups, respectively. Conclusion: Music listening was not
significantly effective in reducing pain during second trimester genetic
amniocentesis.
PMID- 29952500
TI - Vaginal Stump Characteristics after Total Abdominal Hysterectomy Using
Electrosurgery versus Scalpel or Scissors for Vaginal Incision: A Randomized
Controlled Trial.
AB - Objective: To compare the vaginal stump characteristics following total abdominal
hysterectomy between two vaginal incision techniques, electrosurgery versus
scalpel or scissors. Material and Method: A randomized single-blind controlled
trial was performed in 80 patients scheduled to undergo total abdominal
hysterectomy for benign conditions. Either sharp instrument (scalpel or scissors)
or electrosurgery was used for vaginal incision following standard surgical
technique for total abdominal hysterectomy. The main outcome measures were the
vaginal stump characteristics determined by the degree of vaginal mucosal
approximation and the presence of vaginal granulation at 6-week postoperatively.
Results: Six weeks after surgery, the number of patients with incomplete mucosal
approximation following electrosurgical technique was 11 (27.5%), as compared to
8 (20%) (p = 0.43) in the scalpel/scissors technique group. The incidences of
vaginal granulation in the scalpel/scissors group and electrosurgical group were
10% and 22.5%, respectively. Conclusion: The vaginal stump characteristics at six
weeks following total abdominal hysterectomy between two vaginal incision
techniques were not statistically significantly different.
PMID- 29952501
TI - Efficacy of an intimate oil solution containing visnadine in women self-reporting
sexual symptoms.
PMID- 29952502
TI - [In process].
PMID- 29952503
TI - Dietary Counseling Outcomes in Locally Advanced Unresectable or Metastatic Cancer
Patients Undergoing Chemotherapy.
AB - Background: Cancer-related malnutrition led to poor outcomes of treatment,
decreased functional status, decreased quality of life, and delay treatment.
Objective: To examine the effects of dietary counseling for regular foods
consumption on nutritional outcomes in patients with cancer undergoing
chemotherapy. Material and Methods: A prospective randomized study was performed
on locally advanced unresectable or metastatic cancer patients undergoing
chemotherapy at Department of Medicine, Chiang Mai University, between December
2013 and July 2014. Fifty patients were randomly assigned to dietary counseling
group and routine care group. The dietary counseling was performed by a dietitian
before starting chemotherapy. Outcomes were evaluated at the end of three to four
cycles and six to eight cycles of chemotherapy or after two months if the
chemotherapy was stopped earlier. Results: The dietary counseling group
significantly increased percent change of body weight 2.29 (+/-6.20) vs. -1.70
(+/-6.23) percent in the routine care group, p = 0.03 and increased BMI 2.27 (+/
6.09) vs. -1.53 (+/-5.92) percent, p = 0.03 at the end of three to four cycles of
chemotherapy, but there was no significant change at the next two months.
Furthermore, PG-SGA score was lower in the dietary counseling group (6.67 (+/
1.99) vs. 10.04 (+/-3.73), p<0.001, and quality of life was significant increased
in dietary counseling group at the end of three to four cycles of chemotherapy
and at the next two months (score 39.40 (+/-10.61) vs 46.16 (+/-7.55), p = 0.01).
Absolute lymphocyte count, serum albumin, energy intake, number of patients who
delayed chemotherapy, cause of delay chemotherapy, and number of total cycles did
not differ between the groups. Conclusion: Dietary counseling have significantly
improved body weight, BMI, PG-SGA scores, and quality of life scores in patients
with locally advanced unresectable or metastatic cancer undergoing chemotherapy
compared with routine care. We should be concerned about screening for
malnutrition in all cancer patients and we should provide nutritional counseling.
PMID- 29952504
TI - [In process].
PMID- 29952505
TI - Influence of Body Position on Anorectal Manometric Assessment in Functional
Constipation.
AB - Objective: To date, there have been no studies to evaluate the influence of
posture on anorectal manometric measurements in patients with functional
constipation. The present study aimed to compare differences in anorectal
manometric measurements in constipated patients when performing the test in the
lying and sitting positions. Material and Method: Anorectal manometry with a
conventional solid state manometric catheter was performed in 30 constipated
patients in both the lying and sitting positions. Anorectal manometric variables
at rest and during attempted defecation with empty rectum were assessed in both
positions. A colonic transit study using Sitzmarks radiopaque markers and a 50-mL
water-filled balloon expulsion test was also performed in all patients. Patients
exhibiting an abnormal manometric pattern of defecation in either the sitting or
lying position proceeded to a simulated defecation test. The anorectal pressure
parameters of resting and during attempted defecation of the both positions were
compared. Results: The resting rectal pressure, maximum rectal straining
pressure, and defecation index during attempted defecation were significantly
higher in the sitting position than the lying position. A dyssynergic manometric
pattern during attempted defecation with empty rectum was seen in 46% of the
patients in the lying position, not significantly different from the 56% in the
seated position (p = 0.58). Most patients (71%) who exhibited manometric
dyssynergia with an empty rectum could relax their anal sphincter during the
simulated defecation test. Only six (20%) constipated patients had abnormal
dyssynergic anal sphincter contraction confirmed by a simulated defecation test.
Conclusion: Body position affects the results of manometric measurements related
to the defecation mechanism.
PMID- 29952506
TI - [In process].
PMID- 29952507
TI - [In process].
PMID- 29952508
TI - Sepsis and the hematology laboratory. An affordable, widely available test impact
today's biggest healthcare challenge.
PMID- 29952509
TI - [In process].
PMID- 29952511
TI - Point-of-care hemoglobin testing: Methods and relevance to combat anemia.
PMID- 29952510
TI - [In process].
PMID- 29952512
TI - Derivation of an Ambulatory Prognostic Score Chart for Thai Children with
Cerebral Palsy Aged 2 to 18.
AB - Background: Most parents want to know that their children with cerebral palsy
will be able to walk. A simple tool to predict ambulatory status and one uses The
Gross Motor Function Classification System is still lacking. Objective: To
develop a simple prognostic score chart for predicting ambulatory status in Thai
children with cerebral palsy. Material and Method: Four hundred seventy one
children with cerebral palsy aged 2 to 18 registered and treated at six special
schools or hospitals for children with physical disability between 2008 and 2013
were recruited. Baseline characteristics and clinical histories of children with
cerebral palsy were collected from medical and physical therapy records.
Ambulatory status was classified as three ordinal scales by The Gross Motor
Function Classification System - Expanded and Revised version. Results:
Multivariable ordinal continuation ratio logistic regression analysis identified
age, type of cerebral palsy, sitting independently at the age of two, and eating
independently as significant predictors of ambulation. These items were combined
into a clinical prediction score: non-ambulation (scores <7), assisted ambulation
(scores 7 to 8), and independent ambulation (scores >8). Conclusion: The
prognostic tool has high discriminative values of ambulatory status among
children with cerebral palsy. However, the validation of this tool needs to be
tested in other subjects before clinical practice application.
PMID- 29952513
TI - Shifting healthcare needs dictate change for respiratory pathogen diagnostics.
PMID- 29952515
TI - [In process].
PMID- 29952514
TI - Resting Energy Expenditure Measured by Indirect Calorimetry in Infants and Young
Children with Chronic Lung Disease.
AB - Objective: To determine resting energy expenditure (REE) by indirect calorimetry
and to compare measured resting energy expenditure (mREE) by indirect calorimetry
with prediction equations (pREE). Material and Method: Infants and young children
with chronic lung diseases from King Chulalongkorn Memorial Hospital were
enrolled and assessed for nutritional status and severity of chronic lung
diseases. For mREE, indirect calorimetry was performed by custom-made airtight
canopy with O2 and CO2 sensors, with the patients were in a resting state.
Prediction equations were Food and Agriculture/World Health Organization/United
Nations University (FAO/WHO/UNU), Schofield-Weight, Schofield-Weight/Height,
Harris Benedict, and Harris Benedict-Infant equations. Agreement between mREE and
pREE was assessed by Bland-Altman method. Results: Eighteen patients (median age
6 months, range 1 to 26 months) were recruited. Sixteen children had weight for
age Z-score below -2 SD. Median weight for age Z-score, length for age Z-score
and weight for length Z-score were -3.0, -3.1, and -1.9, respectively. Median
mREE was 53.8 kcal/kg/day (interquartile range 47.5 to 72.6 kcal/kg/day). The
Schofield-Weight/Height equation showed the lowest mean of difference at 0.94
kcal/kg/day with 95% confidence interval for the bias -44.4 to 46.3 kcal/kg/day.
Conclusion: To ensure optimal nutritional support, REE should be measured by
indirect calorimetry in pediatric patients with chronic lung diseases. Based on
our finding, the Schofield-Weight/Height equation was the most accurate equation
for predicting REE in this group of patients.
PMID- 29952516
TI - Update on laboratory testing of respiratory viruses with a focus on influenza.
PMID- 29952517
TI - Oncological Outcome of Docetaxel-Based Chemotherapy for Men with Metastatic
Castration-Resistant Prostate Cancer.
AB - Objective: To retrospectively review the oncological outcome of docetaxel-based
chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC).
Material and Method: The present study included 68 patients with mCRPC who were
treated with 3-weekly docetaxel (75 mg/m2) plus prednisone between 2010 and 2014.
The prognostic significance of several clinicopathologic factors in these
patients were analyzed. The endpoints of oncological outcome were overall
survival (OS). The effect of clinical variables on OS was statistically analyzed
by a log-rank test or Cox regression with hazard ratios. All analyses were
performed using a 0.05 level of significance. Results: In these 68 patients, the
median age and serum value of prostate-specific antigen (PSA) prior to docetaxel
based chemotherapy were 69 years and 173 ng/ml, respectively. Of these patients,
PSA decline >=50% was observed in 46 patients (67.6%). The OS and progression
free survival were 25.4 and 11.7 months, respectively. Of several factors
examined, univariate analysis identified PSA at diagnosis mCRPC, PSA at diagnosis
of mCRPC, PSA at first cycle of CMT >=150 ng/mL, number of CMT response <=2 cycle
as significant predictors of OS, of which only PSA at first cycle of CMT >=150
ng/mL appeared to be independently related to poor OS on multivariate analysis.
Conclusion: Oncologic outcomes in mCRPC patients receiving docetaxel-based
chemotherapy is generally favorable and only PSA at first cycle of CMT more than
150 ng/mL appeared to be independently related to poor OS on multivariate
analysis.
PMID- 29952518
TI - Outreach for operational success: How things have evolved.
PMID- 29952520
TI - Outreach 2.0: How times have changed... .
PMID- 29952519
TI - The Effect of Reverse Trendelenburg Position on Incidence of Hypotension after
Spinal Anesthesia.
AB - Objective: To prove if 10-degree head-up tilt position during conduction of
spinal anesthesia and continue through the operation will reduce the incidence of
hypotension comparing to horizontal position in elective cesarean section
parturient. Material and Method: In this randomized double-blind controlled
trial. Forty-four parturient were equally allocated into 10-degree head-up tilt
and horizontal position during conduction of spinal anesthesia and continue
during the operation. Blood pressure, heart rate, incidence of hypotension,
ephedrine consumption, and anesthesia level were compared. Results: Incidence of
hypotension and percentage of parturient that required ephedrine were comparable
in control and study groups (72.73% vs. 45.45%, p = 0.066) but lower before cord
clamping in the study group (68.18% vs. 36.36%, p = 0.03). The sensory block
levels were identical but more parturient in the study group required reposition
in order to gain the required anesthetic level. Conclusion: Ten-degree head-up
tilt position during conduction and maintenance of spinal anesthesia for cesarean
section reduced incidence of hypotension and ephedrine consumption without any
adverse effect in both parturient and newly-born babies.
PMID- 29952521
TI - Thoracic Endovascular Aortic Repair with Chimney Technique (Chimney TEVAR) for
Aortic Arch Pathologies: Cardiovascular Problems during Anesthesia.
AB - Background: Chimney TEVAR is a new alternative surgical treatment for aortic arch
pathologies. As being a developing surgical technique, there might be some
unknown cardiovascular problems during anesthesia. Objective: To investigate
cardiovascular problems during anesthesia. Material and Method: Retrospective
review of medical records between 2010 and 2013 found that chimney TEVAR were
operated in 16 cases. From anesthetic records, cardiovascular parameters were
collected and descriptive statistic and pair-t-test were applied; abnormal events
were focused, traced, and logically depicted. Results: During chimney insertion,
NIBP (at left) were used instead of IBP (at right) in 50% of cases, MAP was
lowest, and CVP was increased. Overall during surgery, decreasing of MAP from
baseline (mean = -36.25+/-21.94 mmHg) was observed throughout the operation and
with statistical significance. Serious cardiovascular instability of 12.5% were
observed. Base on blood transfusion and hematocrit level, the assessed amount of
blood loss was inappropriate and underestimated in 75% of cases. Conclusion: 1)
It was not safe to monitor blood pressure only at right arm, 2) underestimated
assessment of blood loss was common and caused hypotension, 3) volume status was
hardly assessed by basic monitors and CVP did not help for volume assessment, and
4) fatal cardiovascular instability could happen.
PMID- 29952522
TI - The status of laboratory testing for the diagnosis of HIV infection.
PMID- 29952523
TI - Update Psychopharmacotherapy.
AB - Despite unmet meeds regarding efficacy, tolerability and time of onset and the
high importance of mental disorders very few new psychotropics have been
introduced in Germany recently. Lurasidon and the new multimodal antidepressant
vortioxetine demonstrating clinical efficacy in the improvement of cognition have
been withdrawn from the German market due to economic reasons based on an
official committee judgement "missing additional benefit". Among new substances
introduced are the selective opioid modulator nalmefene for reduction of alcohol
consumption, the selective alpha-2-receptor agonist guanfacine for ADHS treatment
in child and youth psychiatry, the older antidepressant milnacipran and the
glucagon-like-peptide-1-receptor agonist liraglutide for treatment of adipositas.
In the USA the atypical antipsychotics cariprazine and brexpiprazole have been
released. The introduction of the long acting depot antipsychotics aripiprazole
(1 month) and paliperidone (3 months) can be seen as major progress in the
treatment of schizophrenia. Loxapine is available as inhalative antipsychotic for
rapid treatment of agitation in schizophrenia and mania. Atypical antipsychotics
like quetiapine are recommended now as add-on treatment for therapy-resistant
depressions. Ketamine and botulinum toxin are in experimental use as
antidepressants. The development of psychotropics is long lasting and costly and
made even more difficult by negative medial attitudes additionally. Constructive
resolving attempts are needed urgently to avoid a standstill in the development
of psychotropic drugs.
PMID- 29952525
TI - Overcoming barriers to digital pathology.
PMID- 29952524
TI - The Prevalence of Red Blood Cell Alloantibodies in Lower Northern Thailand.
AB - Background: Hemolytic transfusion reactions due to the presence of pre-existing
alloantibodies are among the most common immunologic adverse effects in
transfusion medicine. In addition to determining the presence and characteristics
of the specific alloantibodies, one of the major obstacles is the selection of
compatible blood units that lack the corresponding antigens to avoid such
transfusion reactions. A delay in this process can lead to various detrimental
complications. Objective: To characterize the prevalence and specificity of
alloantibodies in patients from lower northern Thailand who required a blood
transfusion. Material and Method: A retrospective review of the Blood Bank
database of Naresuan University, Thailand, was conducted. Thirty one thousand
four hundred patients who had been screened for the presence of alloantibodies
between January 2007 and April 2014 were reviewed. The standard test tube method
was used in all patients to identify the specificity of alloantibodies against
red blood cell surface antigens. Results: Among the 31,400 patients, 169 patients
(0.54%) were found to have pre-existing red blood cell alloantibodies. Anti-Mi
(anti-Miltenberger blood group) was the most common alloantibody identified
(43.79%). Other common alloantibodies were anti-E (18.34%), anti-P1 (17.75%),
anti-Lea (17.16%), and anti-Leb (9.47%). Conclusion: To minimize hemolytic
transfusion reactions, we recommend greater availability and issuing of Mi, E,
P1, Lea, and Leb-matched blood units for patients with known alloantibodies
against these antigens, or for patients who require multiple transfusions. This
is in addition to the standard pre-transfusion screening and cross-matching
processes.
PMID- 29952526
TI - The adaptive bacterial immune system CRISPR-Cas and its therapeutic potential.
AB - The bacterial CRISPR-Cas-system is an adaptive and inheritable immune system for
the defense against invasive genetic elements such as viral DNA or plasmids.
CRISPR-Cas immunity acts by integrating short sequences of non-self DNA in the
cell's CRISPR locus which allows the cell to recognize, to remember and to
destroy the invasive element. In the last years the type-II-system CRISPR-Cas9
was developed as a powerful and universal tool for the sequence-specific
modification of the genome also known as genome editing. Type-II-systems rely
solely on one single protein, Cas9, and a non-coding, trans-activating RNA that
leads the Cas9 protein to its target DNA. The RNA-guided molecular scissor Cas9
is predestinated to correct mutated genes in line with a gene therapy and to heal
chronic diseases like HIV infections or virus-induced forms of cancer via
deleting viral DNA that is integrated as a provirus in the host's genome. In
addition, catalytically inactive Cas9 variants (dCas9) fused to effector domains
can be used to specifically tag genome sections, regulate gene expression and
modify epigenetic markers.
PMID- 29952528
TI - The case for wireless temperature monitoring.
PMID- 29952527
TI - Benefits of automated laboratory environmental monitoring.
PMID- 29952529
TI - Combined use of an ACE-inhibitor and spironolactone in patients with heart
insufficiency.
AB - A patient with cardiac insufficiency takes the ACE-Inhibitor Enalapril as well as
Spironolactone regularly. In the interaction monographs of the German ABDA
database there is a note that combined use of these substances should be avoided
due to an increased risk of hyperkalemia - is there a medication related problem?
There is evidence from clinical studies, that combined use of ACE-inhibitors and
potassium-sparing agents indeed increases the risk of severe hyperkalemia. The
risk seems to be related to the dose of the potassium-sparing agent. However, in
patients with cardiac insufficiency NYHA-class II-IV and an ejection fraction of
<= 35%, the addition of spironolactone to an ACE-inhibitor and betablocking agent
reduces mortality and hospitalization for cardiovascular problems. Therefore the
combination is indicated in these patients. To minimize the risk for severe
adverse events close monitoring of serum potassium and renal function is
mandatory. Moreover, additional risk factors for hyperkalemia such as intake of
potassium supplements or NSAID should be avoided.
PMID- 29952530
TI - The drive to standardize clinical practice for sepsis.
PMID- 29952531
TI - [In process].
PMID- 29952532
TI - So happy together: Integrating molecular and serological testing.
PMID- 29952533
TI - [In process].
PMID- 29952534
TI - [in process].
PMID- 29952535
TI - [In process].
PMID- 29952536
TI - [In process].
PMID- 29952537
TI - [In process].
PMID- 29952538
TI - [In process].
PMID- 29952539
TI - [In prosse].
PMID- 29952540
TI - Li and Mg Co-Doped Zinc Oxide Electron Transporting Layer for Highly Efficient
Quantum Dot Light-Emitting Diodes.
AB - Zinc-oxide (ZnO) is widely used as an n-type electron transporting layer (ETL)
for quantum dot (QD) light-emitting diode (QLED) because various metal doping can
be possible and ZnO nanoparticle can be processed at low temperatures. We report
here a Li- and Mg-doped ZnO, MLZO, which is used for ETL of highly efficient and
long lifetime QLEDs. Co-doping, Mg and Li, in ZnO increases its band gap and
electrical resistivity and thus can enhance charge balance in emission layer
(EML). It is found also that the O-H concentration at the oxide surface decreases
and exciton decay time of QDs on the metal oxide increases by co-doping in ZnO.
The inverted green QLEDs with MLZO ETL exhibits the maximum current efficiency
(CEmax) of 69.1 cd/A, power efficiency (PEmax) of 73.8 lm/W, and external quantum
efficiency (EQEmax) of 18.4%. This is at least two times higher compared with the
efficiencies of the QLEDs with Mg-doped ZnO ETL. The optimum Li and Mg
concentrations are found to be 10% each. The deep-red, red, light-blue, and deep
blue QLEDs with MLZO ETLs exhibit the CEmax of 6.0, 22.3, 1.9, and 0.5 cd/A,
respectively. The MLZO introduced here can be widely used as ETL of highly
efficient QLEDs.
PMID- 29952541
TI - Antifungal Activity of alpha-Sarcin against Penicillium digitatum: Proposal of a
New Role for Fungal Ribotoxins.
AB - Among the putative defense proteins that occur in fungi, one of the best studied
is alpha-sarcin, produced by the mold Aspergillus giganteus. This protein is the
most significant member of the ribotoxin family, which consists of extracellular
rRNA ribonucleases that display cytotoxic activity toward animal cells.
Ribotoxins are rRNA endonucleases that catalyze the hydrolysis of the
phosphodiester bond between G4325 and A4326 from the rat 28S rRNA. The results of
several experimental approaches have led to propose ribotoxins as insecticidal
agents. In this work, we report that alpha-sarcin displays a strong antifungal
activity against Penicillium digitatum, being able to enter into the cytosol
where it inactivates the ribosomes, thus killing the cells and arresting the
growth of the fungus. This is the first time that a ribotoxin has been found to
display antifungal activity. Therefore, this protein could play, besides the
already proposed insecticidal function, a role in nature as an antifungal agent.
PMID- 29952542
TI - How Do Intrinsically Disordered Viral Proteins Hijack the Cell?
PMID- 29952543
TI - Hierarchical Order in Dewetted Block Copolymer Thin Films on Chemically Patterned
Surfaces.
AB - We investigated the dewetting process on flat and chemically patterned surfaces
of ultrathin films (thickness between 2 and 15 nm) of a cylinder forming
polystyrene- block-poly(methyl methacrylate) (PS- b-PMMA) spin coated on
poly(styrene- r-methyl methacrylate) random copolymers (RCPs). When the PS- b
PMMA film dewets on a 2 nm-thick RCP layer, the ordering of the hexagonally
packed PMMA cylinders in the dewetted structures extends over distances far
exceeding the correlation length obtained in continuous block copolymer (BCP)
films. As a result, micrometer-sized circular droplets featuring defectless
single grains of self-assembled PS- b-PMMA with PMMA cylinders perpendicularly
oriented with respect to the substrate are generated and randomly distributed on
the substrate. Additionally, alignment of the droplets along micrometric lines
was achieved by performing the dewetting process on large-scale chemically
patterned stripes of 2 nm thick RCP films by laser lithography. By properly
adjusting the periodicity of the chemical pattern, it was possible to tune and
select the geometrical characteristics of the dewetted droplets in terms of
maximum thickness, contact angle and diameter while maintaining the defectless
single grain perpendicular cylinder morphology of the circular droplets.
PMID- 29952544
TI - Analysis of Dimeric alphabeta Subunit Exchange between PEGylated and Native
Hemoglobins (alpha2beta2 Tetramer) in an Equilibrated State by Intramolecular
betabeta-Cross-Linking.
AB - Various chemical modifications of hemoglobin (Hb) including PEGylation have been
investigated to produce red blood cell substitutes. Some of those modifications
are designed on the premise that the alpha2beta2 tetrameric structure of Hb is
fundamentally stable and that it rarely dissociates into two alphabeta dimers in
a physiological condition. However, in the present work using the "clipping"
method we detected and quantitatively analyzed the considerable degree of
exchange reaction of alphabeta subunits between beta93Cys-bis-PEGylated and
native Hbs through dissociation into alphabeta dimers and restructuring to
alpha2beta2 tetramer in a physiological condition. The equilibrium constant (
Keq) of subunit exchange reactions increased from 0.82 to 2.86 with increasing
molecular weight of PEG from 2 to 40 kDa, indicating that longer PEG chains
enhanced such exchange reaction. The results suggest that the exchange might
occur for other modified Hbs even at a practically high concentration for use as
a red blood cell substitute.
PMID- 29952545
TI - Mechanism of Substrate Recognition and Catalysis of the Haloalkanoic Acid
Dehalogenase Family Member alpha-Phosphoglucomutase.
AB - alpha-Phosphoglucomutase (alphaPGM), in its phosphorylated state, catalyzes the
interconversion of alpha-d-glucose 1-phosphate and alpha-d-glucose 6-phosphate.
The alphaPGM of Lactococcus lactis is a type C2B member of the haloalkanoic acid
dehalogenase (HAD) enzyme family and is comprised of a Rossmann-fold catalytic
domain and inserted alpha/beta-fold cap domain. The active site is formed at the
domain-domain interface. Herein, we report the results from a kinetic-based study
of L. lactis alphaPGM catalysis, which demonstrate enzyme activation by
autocatalyzed phosphorylation of Asp8 with alphaG1P, the intermediacy of
alphaG1,6bisP in the phospho Ll-alphaPGM-catalyzed conversion of alphaG1P to G6P,
and the reorientation of the alphaG1,6bisP intermediate via dissociation to
solvent and rebinding. In order to provide insight into the structural
determinants of L. lactis alphaPGM substrate recognition and catalysis, metal
cofactor and substrate specificities were determined as were the contributions
made by active-site residues toward catalytic efficiency. Lastly, the structure
and catalytic mechanism of L. lactis alphaPGM are compared with those of HAD
family phosphomutases L. lactis beta-phosphoglucomutase and eukayotic alpha
phosphomannomutase to provide insight into the evolution of phosphohexomutases
from HAD family phosphatases.
PMID- 29952546
TI - Extracellular Vesicle Directed Exogenous Ion Channel Transport for Precise
Manipulation of Biological Events.
AB - A larger number of human diseases are related to dysregulation or loss of
cellular functions. Effective restoration of the missing or defective cellular
functions is highly desirable for fundamental research and therapeutic
applications. Inspired by the fantastic feature of cell-derived extracellular
vesicles (EVs) that can transport various bioactive molecules between cells,
herein, we developed a simple and efficient strategy based on EVs for
transferring ion channels to recipient cells, thereby conferring specific
biological function to the target cells and regulating the biological events. The
constructed channel rhodopsin 2 (ChR2)-loaded EV (EV-ChR2) system can mediate the
anchor of light-responsive ion channel ChR2 on the plasma membrane of recipient
cells through membrane fusion. Upon blue light irradiation, the ion channel ChR2
was activated and opened, thus permitting the rapid flux of cation ions (e.g.,
calcium ion) across the plasma membrane of recipient cells. Moreover, the
increased Ca2+ in the cytosol could effectively activate Ca2+-dependent
transcription factors, further triggering the calcium signaling pathway. This
strategy can be extended to modulate other cellular processes and provides a
novel insight on the manipulation of biological events.
PMID- 29952547
TI - Dechlorination of Excess Trichloroethene by Bimetallic and Sulfidated Nanoscale
Zero-Valent Iron.
AB - Nanoscale zerovalent iron (nZVI) likely finds its application in source zone
remediation. Two approaches to modify nZVI have been reported: bimetal (Fe-Me)
and sulfidated nZVI (S-nZVI). However, previous research has primarily focused on
enhancing particle reactivity with these two modifications under more plume-like
conditions. In this study, we systematically compared the trichloroethene (TCE)
dechlorination pathway, rate, and electron selectivity of Fe-Me (Me: Pd, Ni, Cu,
and Ag), S-nZVI, and nZVI with excess TCE simulating source zone conditions. TCE
dechlorination on Fe-Me was primarily via hydrogenolysis while that on S-nZVI and
nZVI was mainly via beta-elimination. The surface-area normalized TCE reduction
rate ( k'SA) of Fe-Pd, S-nZVI, Fe-Ni, Fe-Cu, and Fe-Ag were ~6800-, 190-, 130-,
20-, and 8-fold greater than nZVI. All bimetallic modification enhanced the
competing hydrogen evolution reaction (HER) while sulfidation inhibited HER. Fe
Cu and Fe-Ag negligibly enhanced electron utilization efficiency (epsilone) while
Fe-Pd, Fe-Ni, and S-nZVI dramatically increased epsilone from 2% to ~100%, 69%,
and 72%, respectively. Adsorbed atomic hydrogen was identified to be responsible
for the TCE dechlorination on Fe-Me but not on S-nZVI. The enhanced
dechlorination rate along with the reduced HER of S-nZVI can be explained by that
FeS conducting major electrons mediated TCE dechlorination while Fe oxides
conducting minor electrons mediated HER.
PMID- 29952548
TI - Comparison of Therapeutic Effects of TREK1 Blockers and Fluoxetine on Chronic
Unpredicted Mild Stress Sensitive Rats.
AB - The animal model for depressive behavior due to chronic unpredicted mild stress
(CUMS) is commonly used to evaluate antidepressant treatments. The CUMS model has
faced some criticism because of the heterogeneity of behavioral effects. Spadin
and SID1900 are TREK1 blockers with a quick antidepressant effect. However, to
date, their effectiveness and the long-term therapeutic mechanisms are not known.
We hypothesize that early intervention with TREK1 blockers can fully reverse
depressive-like behaviors, that the chronic administration of TREK1 blockers has
a more pronounced effect than the SSRI fluoxetine, and that its long-term
therapeutic effects may be mediated by improvement of impaired neurogenesis.
Furthermore, we optimized the use of the CUMS model for increased homogeneity by
screening the rats after the CUMS induction procedure. Depressive-like behavior
was assessed by a forced swimming test, sucrose preference, and open field tests.
To evaluate neurogenesis, cell proliferation and newly generated cell apoptosis
were measured in the hippocampal dentate gyrus. Of 32 rats that underwent the
CUMS procedure, 26 rats that exhibited depressive-like behaviors were grouped as
CUMS sensitive rats (CUMSS), while six that did not were grouped as CUMS
resistant ones (CUMSR). The CUMSR rats exhibited minor neurogenesis impairments,
while the CUMSS rats had a more pronounced effect. Treatment with TREK1 blockers
could reverse depressive-like behaviors at least 1 week earlier than that of
fluoxetine. Chronic administration of both the TREK1 blockers and fluoxetine
could restore neurogenesis impairments. This study underlines the importance of
model validation by determination of CUMS sensitivity. The TREK1 blockers were
found to have an effect that was more rapid and more pronounced than that of
fluoxetine. Therapeutic benefits after chronic administration were associated
with a restoration of impaired neurogenesis.
PMID- 29952549
TI - Tile Drainage and Anthropogenic Land Use Contribute to Harmful Algal Blooms and
Microbiota Shifts in Inland Water Bodies.
AB - Freshwater harmful algal blooms (HABs), driven by nutrient inputs from
anthropogenic sources, pose unique risks to human and ecological health
worldwide. A major nutrient contributor is agricultural land use, specifically
tile drainage discharge. Small lakes and ponds are at elevated risk for HAB
appearance, as they are uniquely sensitive to nutrient input. HABs introduce
exposure risk to microcystin (MC), hepatotoxic and potentially carcinogenic
cyanotoxins. To investigate the impact of anthropogenic land use on small lakes
and ponds, 24 sites in central Ohio were sampled over a 3-month period in late
summer of 2015. MC concentration, microbial community structure, and water
chemistry were analyzed. Land use intensity, including tile drainage systems, was
the driver of clustering in principle component analysis, ultimately contributing
to nutrient deposition, a driver of HABs. Relative abundance of HAB-forming
genera was correlated with elevated concentrations of nitrate and soluble
reactive phosphate. One location (FC) showed MC concentrations exceeding 875
MUg/L and large community shifts in ciliates (Oligohymenophorea) associated with
hypoxic conditions. The prokaryotic community at FC was dominated by Planktothrix
sp. These results demonstrate the impact of HABs in small lakes and ponds, and
that prevailing issues extend beyond cyanotoxins, such as cascading impacts on
other trophic levels.
PMID- 29952550
TI - Retention Index Prediction Using Quantitative Structure-Retention Relationships
for Improving Structure Identification in Nontargeted Metabolomics.
AB - Structure identification in nontargeted metabolomics based on liquid
chromatography coupled to mass spectrometry (LC-MS) remains a significant
challenge. Quantitative structure-retention relationship (QSRR) modeling is a
technique capable of accelerating the structure identification of metabolites by
predicting their retention, allowing false positives to be eliminated during the
interpretation of metabolomics data. In this work, 191 compounds were grouped
according to molecular weight and a QSRR study was carried out on the 34
resulting groups to eliminate false positives. Partial least squares (PLS)
regression combined with a Genetic algorithm (GA) was applied to construct the
linear QSRR models based on a variety of VolSurf+ molecular descriptors. A novel
dual-filtering approach, which combines Tanimoto similarity (TS) searching as the
primary filter and retention index (RI) similarity clustering as the secondary
filter, was utilized to select compounds in training sets to derive the QSRR
models yielding R2 of 0.8512 and an average root mean square error in prediction
(RMSEP) of 8.45%. With a retention index filter expressed as +/-2 standard
deviations (SD) of the error, representative compounds were predicted with >91%
accuracy, and for 53% of the groups (18/34), at least one false positive compound
could be eliminated. The proposed strategy can thus narrow down the number of
false positives to be assessed in nontargeted metabolomics.
PMID- 29952551
TI - Orientation Control of Trametes Laccases on a Carbon Electrode Surface to
Understand the Orientation Effect on the Electrocatalytic Activity.
AB - By using a carbon-coated anodic aluminum oxide (CAAO) film as a monolithic porous
electrode for the immobilization of Trametes laccases (LACs), an attempt is made
to control the orientation of LAC molecules toward the electrode surface simply
by applying an electric potential to the CAAO film. Because the resulting film is
characterized by a myriad of open, simple, and straight nanochannels with
diameters as large as 40 nm, the O2 diffusion problem in pores is minimized,
thereby making it possible to highlight the effect of such orientation on the
electrocatalytic activity as a biocathode. It has been evidenced that LAC
molecules are favorably oriented for a smooth electron transfer from the
electrode when the LACs are immobilized with applying a positive voltage to the
electrode, and such favorable orientation exhibits 3.7-times higher
electrocatalytic activity than unfavorable orientation. Furthermore, the
orientation mechanism has been rationally explained in terms of local surface
chemistry on a LAC molecule.
PMID- 29952553
TI - Parathyroid Hormone Senses Extracellular Calcium To Modulate Endocrine Signaling
upon Binding to the Family B GPCR Parathyroid Hormone 1 Receptor.
AB - Parathyroid hormone (PTH) binds to a family B G protein coupled receptor,
parathyroid hormone 1 receptor (PTH1R). One of its functions is to regulate Ca2+
homeostasis in bone remodeling, during which Ca2+ can reach up to 40 mM. A
truncated version of PTH, PTH(1-34), can fully activate PTH1R and has been used
for osteoporosis treatments. Here, we used fluorescence anisotropy to examine the
binding of PTH(1-34) to PTH1R purified in nanodiscs (PTH1R-ND) and found that the
affinity increases 5-fold in the presence of 15 mM Ca2+. However, PTHrP(1-36),
another truncated endogenous agonist for PTH1R, does not show this Ca2+ effect.
Mutations of Glu19 and Glu22 in PTH(1-34) that are not conserved in PTHrP(1-36)
largely abolished the Ca2+ effect. The results support that PTH(1-34) not only
activates PTH1R but also uniquely senses Ca2+. This dual function of a peptide
hormone is a novel observation that couples changes in extracellular environment
with endocrine signaling. Understanding this can potentially reveal the complex
role of PTH signaling in bone remodeling and improve the PTH(1-34) treatment for
osteoporosis.
PMID- 29952552
TI - Ultrahigh-Throughput Production of Monodisperse and Multifunctional Janus
Microparticles Using in-Air Microfluidics.
AB - Compartmentalized Janus microparticles advance many applications ranging from
chemical synthesis to consumer electronics. Although these particles can be
accurately manufactured using microfluidic droplet generators, the per-nozzle
throughputs are relatively low (~MUL/min). Here, we use "in-air microfluidics" to
combine liquid microjets in midair, thereby enabling orders of magnitude faster
production of Janus microparticles (~mL/min) as compared to chip-based
microfluidics. Monodisperse Janus microparticles with diameters between 50 and
500 MUm, tunable compartment sizes, and functional cargo are controllably
produced. Furthermore, these microparticles are designed as magnetically
steerable microreactors, which represents a novel tool to perform enzymatic
cascade reactions within continuous fluid flows.
PMID- 29952554
TI - Assessing the Potential Mechanisms of Isomerization Reactions of Isoprene
Epoxydiols on Secondary Organic Aerosol.
AB - Laboratory and field measurements have demonstrated that isoprene epoxydiol
(IEPOX) is the base component of a wide range of chemical species found in
isoprene-derived secondary organic aerosol (SOA). To address newly raised
questions concerning the chemical identities of IEPOX-derived SOA, the results of
laboratory experiments carried out in bulk aqueous and organic media and analyzed
via nuclear magnetic resonance spectroscopy and computed free energies of
possible products are reported. The IEPOX nucleophilic addition product 2
methyltetrol was found to react too slowly in aqueous solution to explain the
previous observation of tetrahydrofuran-based species. The IEPOX isomerization
reactions in organic media were shown to mainly produce 3-methyltetrahydrofuran
2,4-diols, which were also established by the computational results as one of the
most thermodynamically favorable possible IEPOX reaction products. However, these
isomerization reactions were found to be relatively slow as compared to
nucleophilic addition reactions, indicating that their occurrence on ambient SOA
might be limited to low water content situations. No evidence was found for the
production of the C5 alkene triols or 3-methyltetrahydrofuran-3,4-diols
previously reported for IEPOX reaction on SOA as analyzed via the gas
chromatography/electron ionization-quadrupole mass spectrometry with prior
trimethylsilyl derivatization method.
PMID- 29952555
TI - Low-Temperature Atomic Layer Deposition of Metal Oxide Layers for Perovskite
Solar Cells with High Efficiency and Stability under Harsh Environmental
Conditions.
AB - Rapid progress achieved on perovskite solar cells raises the expectation for
their further development toward practical applications. Moisture sensitivity of
perovskite materials is one of the major obstacles which limits the long-term
durability of the perovskite solar cells, especially in outdoor operation where
rainfall and water accumulation on the solar panels often occur.
Micro/nanopinholes within the functional layers of the devices usually lead to
water vapor penetration, thus subsequent decomposition of perovskites, and
finally poor device performance and shortened operational lifetime. In this work,
low-temperature atomic layer deposition (ALD) technique was utilized to
incorporate pinhole-free metal oxide layers (TiO2 and Al2O3) into an inverted
perovskite solar cell consisting of indium tin
oxide/NiO/perovskite/PC61BM/TiO2/Ag. The interface properties between the
inserted TiO2 layer and the perovskite layer were investigated by X-ray
photoelectron spectroscopy. The results showed that TiO2 ALD fabrication process
had made negligible degradation to the perovskite layer. The TiO2 layer can
significantly reduce interfacial charge recombination loss, improve interfacial
contact, and enhance water resistance. A maximum power conversion efficiency
(PCE) of 18.3% was achieved for devices with TiO2 interface layers. A stacked
Al2O3 encapsulation layer was designed and deposited on top of the devices to
further improve device stability under harsh environmental conditions. The
encapsulated devices with the best performance retained 97% of the initial PCE
after being stored in ambient condition for a thousand hours. They also showed
great water resistance, and no significant degradation in terms of PCE and
photocurrent of the devices was observed after they were immersed in deionized
water for as long as 2 h. Our approach offers a promising way of developing
highly efficient and stable perovskite solar cells under real-world operational
conditions.
PMID- 29952556
TI - Simple Fabrication Method for Mixed Matrix Membranes with in Situ MOF Growth for
Gas Separation.
AB - Metal organic framework (MOF)/polymer composite membranes are of interest for gas
separations, as they often have performance that exceeds the neat polymer.
However, traditional composite membranes, known as mixed matrix membranes (MMMs),
can have complex and time-consuming preparation procedures. The MOF and polymer
are traditionally prepared separately and require priming and mixing to ensure
uniform distribution of particles and compatibility of the polymer-particle
interface. In this study, we reduce the number of steps using an in situ MOF
growth strategy. Herein, MMMs are prepared by growing MOF (UiO-66) in situ within
a Matrimid polymer matrix while simultaneously curing the matrix. The gas
separation performance for MMMs, prepared using this approach, was evaluated for
the CO2/N2 separation and compared with MMMs made using the traditional
postsynthesis mixing. It was found that MMMs prepared using both the in situ MOF
growth strategy and by traditional postsynthesis mixing are equivalent in
performance. However, using the in situ MOF growth allows for a simpler, faster,
and potentially more economical fabrication alternative for MMMs.
PMID- 29952557
TI - Two-Dimensional Thickness-Dependent Avalanche Breakdown Phenomena in MoS2 Field
Effect Transistors under High Electric Fields.
AB - As two-dimensional (2D) transition metal dichalcogenides electronic devices are
scaled down to the sub-micrometer regime, the active layers of these materials
are exposed to high lateral electric fields, resulting in electrical breakdown.
In this regard, understanding the intrinsic nature in layer-stacked 2D
semiconducting materials under high lateral electric fields is necessary for the
reliable applications of their field-effect transistors. Here, we explore the
electrical breakdown phenomena originating from avalanche multiplication in MoS2
field-effect transistors with different layer thicknesses and channel lengths.
Modulating the band structure and bandgap energy in MoS2 allows the avalanche
multiplication to be controlled by adjusting the number of stacking layers. This
phenomenon could be observed in transition metal dichalcogenide semiconducting
systems due to its quantum confinement effect on the band structure. The
relationship between the critical electric field for avalanche breakdown and
bandgap energy is well fitted to a power law curve in both monolayer and
multilayer MoS2.
PMID- 29952558
TI - Modulation of Intracellular O2 Concentration in Escherichia coli Strains Using
Oxygen Consuming Devices.
AB - The use of cell factories for the production of bulk and value-added compounds is
nowadays an advantageous alternative to the traditional petrochemical methods.
Nevertheless, the efficiency and productivity of several of these processes can
improve with the implementation of micro-oxic or anoxic conditions. In the
industrial setting, laccases are appealing catalysts that can oxidize a wide
range of substrates and reduce O2 to H2O. In this work, several laccase-based
devices were designed and constructed to modulate the intracellular oxygen
concentration in bacterial chassis. These oxygen consuming devices (OCDs)
included Escherichia coli's native laccase (CueO) and three variants of this
protein obtained by directed evolution. The OCDs were initially characterized in
vitro using E. coli DH5alpha protein extracts and subsequently using extracts
obtained from other E. coli strains and in vivo. Upon induction of the OCDs, no
major effect on growth was observed in four of the strains tested, and analysis
of the cell extract protein profiles revealed increased levels of laccase.
Moreover, oxygen consumption associated with the OCDs occurred under all of the
conditions tested, but the performance of the devices was shown to be strain
dependent, highlighting the importance of the genetic background even in closely
related strains. One of the laccase variants showed 13- and 5-fold increases in
oxidase activity and O2 consumption rate, respectively. Furthermore, it was also
possible to demonstrate O2 consumption in vivo using l-DOPA as the substrate,
which represents a proof of concept that these OCDs generate an intracellular
oxygen sink, thereby manipulating the redox status of the cells. In addition, the
modularity and orthogonality principles used for the development of these devices
allow easy reassembly and fine-tuning, foreseeing their introduction into other
chassis/systems.
PMID- 29952559
TI - Electrochemical Formation of Divalent Samarium Cation and Its Characteristics in
LiCl-KCl Melt.
AB - The electrochemical reduction of trivalent samarium in a LiCl-KCl eutectic melt
produced highly stable divalent samarium, whose electrochemical properties and
electronic structure in the molten salt were investigated using cyclic
voltammetry, UV-vis absorption spectroscopy, laser-induced emission spectroscopy,
and density functional theory (DFT) calculations. Diffusion coefficients of Sm2+
and Sm3+ were electrochemically measured to be 0.92 * 10-5 and 1.10 * 10-5 cm2/s,
respectively, and the standard apparent potential of the Sm2+/3+ couple was
estimated to be -0.82 V vs Ag|Ag+ at 450 degrees C. The spectroelectrochemical
study demonstrated that the redox behavior of the samarium cations obeys the
Nernst equation ( E degrees ' = -0.83 V, n = 1) and the trivalent samarium cation
was successfully converted to the divalent cation having characteristic
absorption bands at 380 and 530 nm with molar absorptivity values of 1470 and 810
M-1 cm-1, respectively. Density function theory calculations for the divalent
samarium complex revealed that the absorption signals originated from the 4f6 to
4f55d1 transitions. Additionally, laser-induced emission measurements for the Sm
cations in the LiCl-KCl matrix showed that the Sm3+ ion in the LiCl-KCl melt at
450 degrees C emitted an orange color of fluorescence, whereas a red colored
emission was observed from the Sm2+ ion in the solidified LCl-KCl salt at room
temperature.
PMID- 29952560
TI - Ionic Organic Small Molecules as Hosts for Light-Emitting Electrochemical Cells.
AB - Light-emitting electrochemical cells (LEECs) from ionic transition-metal
complexes (iTMCs) offer the potential for high-efficiency electroluminescence in
a simple, single-layer device. However, LEECs typically rely on the use of rare
metal complexes. This has limited their cost effectiveness and put constraints on
their applicability. With a view to leveraging the efficient emission of these
complexes while mitigating costs, we describe here a host/guest LEEC strategy
that relies on the use of carbazole (Cz)-based organic small-molecule hosts and
iTMC guests. Three cationic host molecules were prepared via the coupling of 1-(4
bromophenyl)-2-phenylbenzimidazole (PBI-Br) with Cz. This has allowed a
comparison between the hosts bearing methoxy (PBI-CzOMe) and tert-butyl (PBI-Cz
tBu) substituents, as well as an unsubstituted analogue (PBI-CzH). Cyclic
voltammetry and UV-visible absorption revealed that all three host materials have
wide band gaps characterized by reversible oxidation and irreversible reduction
events. On the basis of electronic structure calculations, the host highest
occupied molecular orbital (HOMO) resides primarily on the Cz moiety, whereas the
lowest unoccupied molecular orbital (LUMO) is located primarily on the phenyl
benzimidazolium unit. Photoluminescence analysis of thin-film blends of PBI-CzH
with iTMC guests confirmed that the emission was blue-shifted relative to
pristine iTMC films, which is consistent with what was seen in dilute
dichloromethane solution. LEEC devices were prepared based on thin films of the
pristine hosts, pristine guests, and 90%/10% (w/w) host/guest blends. Among these
host/guest blends, LEECs based on PBI-CzH displayed the best performance,
particularly when an iridium complex was used as the guest. The system in
question yielded a luminance maximum of 624 cd/m2 at an external quantum
efficiency of 3.80%. This result stands in contrast to what is seen with typical
organic light-emitting diode host studies, where tert-butyl substitution of the
host generally leads to a better performance. To rationalize the present
observations, the host materials were subject to single-crystal X-ray diffraction
analysis. The resulting structures revealed clear head-to-tail interactions in
the case of both PBI-CzH and PBI-CzOMe. No such interactions were evident in the
case of PBI-Cz tBu. Furthermore, PBI-CzH showed a relatively smaller spacing
between the successive HOMO and successive LUMO levels relative to PBI-CzOMe and
PBI-Cz tBu, a finding consistent with more favorable charge transport and energy
transfer. The results presented here can help inform the design and preparation
of host materials suitable for use in single-layer iTMC LEECs.
PMID- 29952561
TI - Carbene Complexes of Stannocenes.
AB - Several stannocene carbene complexes, 3a-3g, were synthesized and examined in
solution by NMR spectroscopy and in the solid state by single-crystal X-ray
diffraction. In this new class of metallocene carbene complexes, coordination of
the carbene to the tin atom was found to be comparably weak and mostly due to
attractive dispersion forces, as indicated by density functional theory
calculations. Furthermore, coordination of the N-heterocyclic carbenes results in
a weakening of the Sn-Cp bonds, making these complexes very reactive and short
lived at room temperature.
PMID- 29952562
TI - Chemically-Controlled Stacking of Inorganic Subnets in Coordination Networks:
Metal-Organic Magnetic Multilayers.
AB - Coordination networks (CNs), such as, for instance, metal-organic frameworks
(MOFs), can turn into remarkable magnets, with various topologies of spin
carriers and unique opportunities of cross-coupling to other functionalities.
Alternatively, distinct inorganic subnetworks that are spatially segregated by
organic ligands can lead to coexisting magnetic systems in a single bulk
material. Here, we present a system of two CNs of general formula Mn(H2O) x(OOC
(C6H4) y-COO). The compound with two water molecules and one aromatic ring ( x =
2; y = 1) has a single two-dimensional magnetic subnet, while the material with x
= 1.5 and y = 2 shows, additionally, another type of magnetic layer. In analogy
to magnetic multilayers that are deposited by physical methods, these materials
can be regarded as metal-organic magnetic multilayers (MOMMs), where the stacking
of different types of magnetic layers is controlled by the choice of an organic
ligand during the chemical synthesis. This work further paves the way toward
organic-inorganic nanostructures with functional magnetic properties.
PMID- 29952564
TI - Photochemical Structural Transformation of a Linear 1D Coordination Polymer
Impacts the Electrical Conductivity.
AB - A pair of 4-(1-naphthylvinyl)pyridine (4-nvp) ligands has been successfully
aligned in head-to-tail fashion in a one-dimensional (1D) double chain ladder
polymer [Cd(adc)(4-nvp)2(H2O)] n (1; H2adc = acetylenedicarboxylic acid) that
undergoes a photochemical [2 + 2] cycloaddition reaction accompanied by single
crystal to single-crystal (SCSC) structural transformation from a 1D chain to a
2D layer structure. These structural changes have a significant impact on the
conductivity and Schottky nature of the compound.
PMID- 29952563
TI - The Role of Metal Halide Perovskites in Next-Generation Lighting Devices.
AB - The development of smart illumination sources represents a central challenge for
current technology. In this context, the quest for novel materials that enable
efficient light generation is essential. Metal halide compounds with perovskite
crystalline structure (ABX3) have gained tremendous interest in the last five
years since they come as easy-to-prepare high performance semiconductors.
Perovskite absorbers are driving the power-conversion-efficiencies of thin film
photovoltaics to unprecedented values. Nowadays, mixed-cation, mixed-halide lead
perovskite solar cells reach efficiencies consistently over 20% and promise to
get close to 30% in multijunction devices when combined with silicon cells at no
surcharge. Nonetheless, perovskites' fame extends further since extensive
research on these novel semiconductors has also revealed their brightest side.
Soon after their irruption in the photovoltaic scenario, demonstration of
efficient color tunable-with high color purity-perovskite emitters has opened new
avenues for light generation applications that are timely to discuss herein.
PMID- 29952565
TI - Deoxynucleoside Triphosphate Containing Pyridazin-3-one Aglycon as a Thymidine
Triphosphate Substitute for Primer Extension and Chain Elongation by Klenow
Fragments.
AB - Deoxynucleoside 5'-triphosphate was synthesized with 3-oxo-2 H-pyridazin-6-yl
(PzO)-a uracil analogue lacking a 2-keto group-as the nucleobase. Theoretical
analyses and hybridization experiments indicated that PzO recognizes adenine (A)
for formation of a Watson-Crick base pair. Primer extension reactions using
nucleoside 5'-triphosphate and the Klenow fragment revealed that the synthetic
nucleoside 5'-triphosphate was incorporated into the 3' end of the primer through
recognition of A in the template strand. Moreover, the 3'-nucleotide residue
harboring PzO as the base was resistant to the 3'-exonuclease activity of Klenow
fragment exo+. The primer bearing the PzO base at the 3' end could function in
subsequent chain elongation. These properties of PzO were attributed to the
presence of an endocyclic nitrogen atom at the position ortho to the glycosidic
bond, which was presumed to form an H-bond with the amino acid residue of DNA
polymerase for effective recognition of the 3' end of the primer for primer
extension. These results provide a basis for designing new nucleobases by
combining a nitrogen atom at the position ortho to the glycosidic bond and base
pairing sites for Watson-Crick hydrogen bonding.
PMID- 29952566
TI - Ternary CuZnS Nanocrystals: Synthesis, Characterization, and Interfacial
Application in Perovskite Solar Cells.
AB - Ternary CuZnS nanocrystals (NCs) are synthesized via a facile, scalable,
noninjection method at low temperatures for the first time, wherein sodium
ascorbate plays the dual roles of reducing agent and capping ligand in the
preparation process. These NCs can be dispersed well in a polar solvent like
dimethyl sulfoxide, and the average size is ~4 nm as measured by transmission
electron microscopy. The results of X-ray diffraction and X-ray photoelectron
spectroscopy indicate that the crystal structure of CuZnS NCs displays covellite
CuS-like structure and the Zn element partly occupies the Cu position. Also, the
crystal structure of CuZnS NCs is completely converted from a covellite CuS
structure into a digenite Cu9S5 structure when the NCs are treated above 350
degrees C. Moreover, CuZnS NCs demonstrate favorable hole transport properties.
When it is employed in MAPbI3-based perovskite solar cells as a hole transport
layer, a peak power conversion efficiency of 18.3% is achieved. Simultaneously,
the devices based on CuZnS exhibit a remarkably reduced J-V hysteresis. The
results indicate that CuZnS is a promising hole transport layer for enhancing
perovskite solar cell performance and presents great potential for optoelectronic
applications, as well.
PMID- 29952568
TI - Approach to Chiral 1-Substituted Isoquinolone and 3-Substituted Isoindolin-1-one
by Addition-Cyclization Process.
AB - An approach to access 1-substituted isoquinolones has been developed through the
addition-cyclization of imines with Grignard reagents in the presence of 2,2'
dipyridyl. A number of substituted aromatic magnesium reagents were amenable to
this process, and the desired products were obtained with excellent yields and
outstanding diastereoselectivities ( dr > 99:1). The utility of this convenient
approach is demonstrated by the formal synthesis of ( S)-cryptostyline II.
Moreover, N-methylmorpholine (NMM) was found to be an effective additive for the
formation of 3-substituted isoindolin-1-ones using one-pot addition-cyclization
deprotection of imine with Grignard reagents.
PMID- 29952567
TI - Discovery of a Potent, Orally Bioavailable PI4KIIIbeta Inhibitor (UCB9608) Able
To Significantly Prolong Allogeneic Organ Engraftment in Vivo.
AB - The primary target of a novel series of immunosuppressive 7-piperazin-1
ylthiazolo[5,4- d]pyrimidin-5-amines was identified as the lipid kinase,
PI4KIIIbeta. Evaluation of the series highlighted their poor solubility and
unwanted off-target activities. A medicinal chemistry strategy was put in place
to optimize physicochemical properties within the series, while maintaining
potency and improving selectivity over other lipid kinases. Compound 22 was
initially identified and profiled in vivo, before further modifications led to
the discovery of 44 (UCB9608), a vastly more soluble, selective compound with
improved metabolic stability and excellent pharmacokinetic profile. A co-crystal
structure of 44 with PI4KIIIbeta was solved, confirming the binding mode of this
class of inhibitor. The much-improved in vivo profile of 44 positions it as an
ideal tool compound to further establish the link between PI4KIIIbeta inhibition
and prolonged allogeneic organ engraftment, and suppression of immune responses
in vivo.
PMID- 29952569
TI - Grain Boundaries Are Benign and Suppress Nonradiative Electron-Hole Recombination
in Monolayer Black Phosphorus: A Time-Domain Ab Initio Study.
AB - Using time-domain density functional theory combined with nonadiabatic molecular
dynamics, we demonstrate that both symmetrical (GB_s) and asymmetrical grain
boundaries (GB_a) significantly extend charge-carrier lifetime compared with
monolayer black phosphorus. Boundaries create no deep trap states, which decrease
electron-phonon coupling. As a result, GB_s increases carrier lifetime by a
factor of 22, whereas GB_a extends the lifetime by a factor of 4. More
importantly, the interplay between the immobile electron localized at the
boundaries in the GB_s and extended excited-state lifetime facilitates a chemical
reaction, which is beneficial for photocatalysts. In contrast, GB_a separates
electron and hole spatially in different locations, which forms a long-lived
charge-separated state and is favorable for photovoltaics. Our simulations
demonstrate that grain boundaries are benign and retard nonradiative electron
hole recombination in monolayer black phosphorus, suggesting a route to reduce
energy losses via rational choice of defect to realize high-performance
photovoltaic and photocatalytic devices.
PMID- 29952570
TI - Game of Frontier Orbitals: A View on the Rational Design of Novel Charge-Transfer
Materials.
AB - Since the first application of frontier molecular orbitals (FMOs) to rationalize
stereospecificity of pericyclic reactions, FMOs have remained at the forefront of
chemical theory. Yet, the practical application of FMOs in the rational design
and synthesis of novel charge transfer materials remains under-appreciated. In
this Perspective, we demonstrate that molecular orbital theory is a powerful and
universal tool capable of rationalizing the observed redox/optoelectronic
properties of various aromatic hydrocarbons in the context of their application
as charge-transfer materials. Importantly, the inspection of FMOs can provide
instantaneous insight into the interchromophoric electronic coupling and polaron
delocalization in polychromophoric assemblies, and therefore is invaluable for
the rational design and synthesis of novel materials with tailored properties.
PMID- 29952571
TI - De Novo Design of Excited-State Intramolecular Proton Transfer Emitters via a
Thermally Activated Delayed Fluorescence Channel.
AB - Developing excited-state intramolecular proton transfer (ESIPT) emitters with
high photoluminescence quantum yields (PhiPLs) and long fluorescence lifetimes in
solid state remains a formidable challenge. In this study, we integrated the
molecular design tactics of thermally activated delayed fluorescence (TADF) into
ESIPT molecules with the goals of improving their PhiPLs and increasing their
fluorescence lifetimes. Two proof-of-concept molecules, PXZPDO and DMACPDO, were
developed by adopting symmetric D-pi-A-pi-D molecular architectures (where D and
A represent donors and acceptors, respectively) featuring electron-donating
phenoxazine or a 9,9-dimethyl-9,10-dihydroacridine moiety, an ESIPT core beta
diketone, and phenylene pi-bridges. Both molecules exhibited sole enol-type forms
stabilized by intramolecular hydrogen bonds and exhibited a unique and dynamic
ESIPT character that was verified by transient absorption analyses. Endowed with
distinct TADF features, PXZPDO and DMACPDO showed high PhiPLs of 68% and 86% in
the film state, coupled with notable delayed fluorescence lifetimes of 1.33 and
1.94 MUs, respectively. Employing these ESIPT emitters successfully achieved
maximum external quantum efficiencies (etaexts) of 18.8% and 23.9% for yellow and
green organic light-emitting diodes (OLEDs), respectively, which represent the
state-of-the-art device performances for ESIPT emitters. This study not only
opens a new avenue for designing efficient ESIPT emitters with high PhiPLs and
long fluorescence lifetimes in solid state but also unlocks the huge potential of
ESIPT emitters in realizing high-efficiency OLEDs.
PMID- 29952572
TI - Phosphine-Catalyzed Enantioselective [4 + 2] Cycloaddition-Semipinacol-Type
Rearrangement Reaction of Morita-Baylis-Hillman Carbonates.
AB - The chiral phosphine-triggered electrophilic ylide intermediate for a Morita
Baylis-Hillman carbonates activation strategy provides a promising method for the
design of organocatalytic intermolecular higher-order annulation processes.
PMID- 29952573
TI - A Unified Strategy for the Syntheses of the Isoquinolinium Alkaloids Berberine,
Coptisine, and Jatrorrhizine.
AB - Total syntheses of the antibacterial alkaloids berberine, coptisine, and
jatrorrhizine have been achieved in four steps through a unified route. The key
step of this strategy is an efficient intramolecular Friedel-Crafts
alkoxyalkylation which, following oxidation, establishes the isoquinolinium core
of these natural products. Herein, the design and development of this synthetic
strategy, which has enabled the shortest and most efficient syntheses of these
alkaloids reported to date, is described.
PMID- 29952574
TI - Synthesis of 1,2,4-Triazol-3-imines via Selective Stepwise Cycloaddition of
Nitrile Imines with Organo-cyanamides.
AB - A convenient method for the synthesis of 1,2,4-triazol-3-imines through a
selective, formal, 1,3-dipolar cycloaddition of organo-cyanamide ions with
nitrile imine dipoles is reported. Hydrolysis of the 1,2,4-triazol-3-imines
yields the corresponding 1,2,4-triazol-5-ones. A stepwise mechanism, supported by
DFT calculations, is invoked to explain the reaction selectivity.
PMID- 29952575
TI - Templating Colloidal Crystal Growth Using Chirped Surface Relief Gratings.
AB - We report a method for controlling the lattice geometry of monodisperse colloidal
crystals formed by confined convective self-assembly on a substrate patterned
with a chirped surface relief grating. Chirped gratings were fabricated using
laser interference lithography and a curved mirror reflector to create
photoresist patterns with pitch values ranging from ~500 to >10 000 nm spread
over a planar surface. These surface nanostructures are shown to guide the
formation of various lattice geometries not normally found via colloidal assembly
on planar surfaces. It is shown that when the pitch of the grating is much larger
than the diameter of the colloidal particles, the grating trenches serve as
compartments for deposition and the particles form close-packed, linear chains.
Various ordered structures are observed as the dimensions of the grating pitch
decrease and approach the diameter of the particles. The grating nanostructures
guide the formation of various lattice geometries due to specific particle
surface and particle-particle interactions. Observed crystal lattices include
square, hexagonal, and rhombic structures. The formation of these structures is
explained in terms of the geometrical constraints imposed by the surface pattern
and the particle diameter. These crystal lattices can be translated into large
area samples when using corresponding single-pitch grating substrates. The
initial monolayer lattice can also serve as a template for the growth of unique,
bilayer structures that include rectangular lattices, chains of particle pairs or
triplets, and graphitelike structured lattices. In addition, when coated with a
thin silver layer, these various lattice configurations are shown to produce
optical reflection features that are precisely controlled by the underlying
structure as it varies from widely spaced particle chains to close-packed lattice
geometries.
PMID- 29952576
TI - Using reappraisal to regulate negative emotion after the 2016 U.S. Presidential
election: Does emotion regulation Trump political action?
AB - Political action (volunteering, protesting) is central to functioning
democracies, and action is often motivated by negative emotion. However, theories
of emotion regulation suggest that people often strive to decrease such negative
emotions. Thus, effective emotion regulation (e.g., reappraisal)-while helping
people feel better-could have the unintended consequence of hindering political
action. We tested this hypothesis in Clinton voters after the 2016 U.S. election
(Ntotal = 1552). Studies 1a (conducted November 2016) and 1b (conducted November
2016, with a follow-up in January 2017) assessed individuals' recent use of
reappraisal in managing emotions evoked by the election. Studies 2a and 2b
(conducted March 2017) exposed individuals to Trump-focused news footage and
assessed individuals' reappraisal during the clip and subsequent emotional
responses. Studies 3a and 3b (conducted June 2017) experimentally manipulated
reappraisal and measured subsequent emotional responses to Trump-focused news
footage. Each study assessed recent or intended political action. In Studies 1a
and 1b, we found that reappraisal predicted lower political action; in Studies 2a
and 2b we observed an indirect effect such that reappraisal predicted lower
negative emotion which in turn accounted for lower intentions to engage in
political action; and Studies 3a and 3b provided experimental evidence for this
indirect effect. These results suggest that effective emotion regulation like
reappraisal may be beneficial in the short-run by helping restore emotional well
being after upsetting political events but may also be costly in the long-run by
reducing the potential for productive political action. (PsycINFO Database Record
PMID- 29952577
TI - Thinking about a new decade in life increases personal self-reflection: A
replication and reinterpretation of Alter and Hershfield's (2014) findings.
AB - Alter and Hershfield (2014) recently published a set of studies suggesting that
people often search for existential meaning as they approach a new decade in
chronological age. The purpose of the current research was to replicate their
experimental study (Study 2 in their article) and extend their findings using
additional operational measures of search for meaning. Study 1 was a replication
comparing the two conditions used in the original study (i.e., experimental and
baseline control), whereas Studies 2 and 3 were direct replications of the
original methods using all three conditions (i.e., experimental, baseline
control, and birthday control). All replications found general support for the
original claims with important caveats. Specifically, whereas Studies 1 and 3
replicated their main findings, Study 2 did not. Importantly, however, a factor
analysis of Alter and Hershfield's meaning-seeking measure revealed two factors
underlying a search for meaning: life-reflection and perceived value of meaning.
Across all studies, findings suggest that people are significantly more likely to
engage in a life review as they begin a new epoch in their lives while there were
no differences in their perceived value of meaning. A reinterpretation of Alter
and Hershfield's findings is discussed. (PsycINFO Database Record
PMID- 29952578
TI - Age in the entrepreneurial process: The role of future time perspective and prior
entrepreneurial experience.
AB - Combining the life span developmental perspective with the process perspective of
entrepreneurship, we develop hypotheses on the role of age in the entrepreneurial
process. Specifically, we expect that younger people have a more extensive future
time perspective than older people, which makes it more likely for younger (vs.
older) people to transition from opportunity identification to forming
entrepreneurial intentions. Further, we expect that older people have greater
prior entrepreneurial experience than younger people, which makes it more likely
for older (vs. younger) people to transition from forming entrepreneurial
intentions to engaging in entrepreneurial activity. We tested our hypotheses
using longitudinal data from 343 working adults from Australia across 12 months
with 3 measurement waves. Results supported our hypotheses. Our findings suggest
that age-related constructs can facilitate and hinder transitions in the
entrepreneurial process. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29952579
TI - A measure of school racial socialization and quality of intergroup interactions.
AB - OBJECTIVES: The current study presents a comprehensive framework of campus racial
climate and tests the validity and reliability of a new measure, the School
Climate for Diversity Scale-College, in three independent samples. The scale
measures 10 dimensions of campus racial climate in the two domains of intergroup
interactions (frequency of interaction, quality of interaction, equal status,
support for positive interaction, and stereotyping) and campus racial
socialization (cultural socialization, mainstream socialization, promotion of
cultural competence, colorblind socialization, and critical consciousness
socialization). METHOD: Participants were college students drawn from an online
task system and a public university on the West Coast. RESULTS AND CONCLUSIONS:
Study 1 provided evidence of reliability and validity with existing measures of
college climate, whereas Study 2 provided evidence of factor stability through
exploratory factor analysis as well as additional evidence of discriminant and
concurrent validity. Finally, Study 3 replicated the factor structure of Study 2
and provided further evidence of validity. (PsycINFO Database Record
PMID- 29952580
TI - At what costs? Student loan debt, debt stress, and racially/ethnically diverse
college students' perceived health.
AB - OBJECTIVES: There has been little research on the direct and indirect connections
between student loan debt and health. The present study tested a transactional
stress model (Lazarus & Folkman, 1984a) of student loan debt in which the
appraisal of debt as stressful was proposed to mediate the associations between
student loan debt amount and perceived health (i.e., self-rated general health,
depressive symptomatology). METHOD: The present study draws on a
racially/ethnically diverse college student sample (N = 1,412) from the National
Longitudinal Survey of Freshman (NLSF). Structural equation modeling (SEM) with
robust maximum likelihood (MLR) estimation was used to test the fit of the
transactional stress model and compare it with an alternative model (that is,
Schachter and Singer's (1962) two factor). Multigroup analyses were conducted to
test racial/ethnic differences. RESULTS: SEM results indicated good fit of the
transactional stress model and suggested its superiority to the alternative two
factor model. Multigroup SEM analyses revealed racial/ethnic differences. Whereas
for Black/African Americans, Hispanic/Latino Americans, and White Americans,
appraisal of debt as stressful was linked to poorer general health and more
depressive symptomatology, these associations were nonsignificant for Asian
Americans. Tests of indirect effects indicated that the mediating role of debt
stress was most consistently significant for Black/African Americans and
Hispanic/Latino Americans compared with Asian and, to a lesser extent, White
Americans. CONCLUSIONS: Results affirm the potential health impact of both
student loan debt amount and the subjective appraisal of stress associated with
student loan debt as significant stressors. (PsycINFO Database Record (c) 2018
APA, all rights reserved).
PMID- 29952581
TI - Anxiety sensitivity and acculturative stress among trauma exposed Latinx young
adults.
AB - There are elevated rates of trauma exposure, posttraumatic stress symptoms, and
greater conditional risk of posttraumatic stress disorder among Latinx relative
to other racial/ethnic groups. Such trauma-related health disparities serve to
exacerbate or maintain acculturative and other types of stress among the Latinx
population. Yet, little research has explored what types of individual difference
factors may undergird variability in acculturative stress among trauma-exposed
Latinx persons. Accordingly, the present investigation examined individual
differences in anxiety sensitivity (fear of the negative consequences of stress
sensations) in relation to acculturative stress among a large sample of trauma
exposed Latinx young adults (n = 1,377 persons; Mage = 21.01; SD = 2.50; age
range: 18-29 years; 76.7% female). Results demonstrated that anxiety sensitivity
explained 10.2% of unique variance in acculturative stress (p < .001, adjusted R2
= .188) after accounting for age, sexual minority status, history of trauma
exposure, and posttraumatic stress symptom severity. Additionally, each of the 3
subfactors of anxiety sensitivity (Physical, Cognitive, and Social) were directly
related to acculturative stress despite sharing variance with one another.
Overall, the current findings suggest that anxiety sensitivity may be a
heretofore underrecognized individual difference factor that is related to more
severe acculturative stress among trauma-exposed Latinx young adults. (PsycINFO
Database Record (c) 2018 APA, all rights reserved).
PMID- 29952582
TI - Workplace climate and satisfaction in sexual minority populations: An application
of social cognitive career theory.
AB - Workplace sexual identity management has drawn increasing attention in the
counseling psychology literature. Disclosing a sexual minority identity at work
may lead to greater levels of work satisfaction, but it may also lead to
occupational barriers (e.g., lack of advancement opportunities, interpersonal
harassment) when disclosing in nonaffirming workplace environments. The present
study used social-cognitive career theory (SCCT)'s self-management model with a
sample of 214 American sexual minority employees recruited via Facebook to
examine the adaptive nature of workplace sexual identity management and its
resulting impact on work satisfaction. The present model employed path analysis
to hypothesize more affirmative workplace environments lead to greater levels of
identity disclosure through the mediating variables of disclosure self-efficacy
and outcome expectations. Further, the model posited workplace climate moderates
the relationship between sexual identity disclosure and work satisfaction such
that work satisfaction increases in the presence of both an affirming workplace
climate and employee's decision to self-disclose. Results largely supported all
hypotheses and demonstrate continued use of SCCT's self-management model for
examining sexual identity management while also highlighting the importance of
both an affirming workplace climate and factors that influence an employee's
decision to self-disclose. Specifically, the relationship between identity
disclosure and work satisfaction was strongest in the presence of more affirming
workplace environments. These findings provide support for inclusive workplace
policies such as nondiscrimination ordinances in order to maximize sexual
minority work satisfaction. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29952583
TI - Customer mistreatment harms nightly sleep and next-morning recovery: Job control
and recovery self-efficacy as cross-level moderators.
AB - Customer mistreatment is becoming an important topic for work stress researchers
and practitioners given the rise of service industry. Taking stressor-emotion
control perspectives, the authors examine day-level relationships between call
center workers' customer mistreatment experiences and their impaired recovery
outcomes mediated by end-of-work negative affect. Furthermore, control concepts
in the job and personal domains are tested as cross-level moderators.
Specifically, job control and recovery self-efficacy are identified to reduce the
within-person process of customer mistreatment affecting recovery outcomes.
Seventy-one call center employees completed a registration survey and then two
daily surveys over 2 consecutive weeks, yielding 481 time-lagged day-level
observations. Multilevel path analyses show that customer mistreatment is
positively associated with increased negative affect, which, in turn, predicts
poor sleep quality at night and poor recovery state the next morning. Job control
attenuates the day-level effect of customer mistreatment on negative affect, and
recovery self-efficacy alleviates the day-level effects of negative affect on
sleep quality and next-morning recovery state. The findings shed light on the
recovery-impairing effects of customer mistreatment and its important boundary
conditions. (PsycINFO Database Record
PMID- 29952584
TI - Predicting while comprehending language: A theory and review.
AB - Researchers agree that comprehenders regularly predict upcoming language, but
they do not always agree on what prediction is (and how to differentiate it from
integration) or what constitutes evidence for it. After defining prediction, we
show that it occurs at all linguistic levels from semantics to form, and then
propose a theory of which mechanisms comprehenders use to predict. We argue that
they most effectively predict using their production system (i.e., prediction-by
production): They covertly imitate the linguistic form of the speaker's utterance
and construct a representation of the underlying communicative intention.
Comprehenders can then run this intention through their own production system to
prepare the predicted utterance. But doing so takes time and resources, and
comprehenders vary in the extent of preparation, with many groups of
comprehenders (non-native speakers, illiterates, children, and older adults)
using it less than typical native young adults. We thus argue that prediction-by
production is an optional mechanism, which is augmented by mechanisms based on
association. Support for our proposal comes from many areas of research
(electrophysiological, eye-tracking, and behavioral studies of reading, spoken
language processing in the context of visual environments, speech processing, and
dialogue). (PsycINFO Database Record
PMID- 29952586
TI - Reduced mind-wandering in mild cognitive impairment: Testing the spontaneous
retrieval deficit hypothesis.
AB - OBJECTIVE: Research on early cognitive markers of Alzheimer's disease (AD) is
primarily focused on declarative episodic memory tests that involve deliberate
and effortful/strategic processes at retrieval. The present study tested the
spontaneous retrieval deficit hypothesis, which predicts that people with
amnestic mild cognitive impairment (aMCI), who are at increased risk of
developing AD, are particularly impaired on tasks that rely on spontaneous
retrieval processes. METHOD: Twenty-three participants with aMCI and 25 healthy
controls (HC) completed an easy vigilance task and thought probes (reporting what
was going through their mind), which were categorized as spontaneous thoughts
about the past (i.e., involuntary memories), current situation, and future (i.e.,
spontaneous prospection). RESULTS: Participants with aMCI reported significantly
fewer spontaneous thoughts or mind-wandering than HC. This effect was driven by
significantly fewer involuntary memories, although groups did not differ in the
number of current and future thoughts. CONCLUSIONS: Findings provide strong
support for the spontaneous retrieval deficit hypothesis. Implications for
research on mind-wandering and the default network, early cognitive markers of
the disease, and our theoretical understanding of the nature of cognitive
deficits in AD are discussed. (PsycINFO Database Record
PMID- 29952585
TI - Categorization system-switching deficits in typical aging and Parkinson's
disease.
AB - OBJECTIVE: Numerous studies documenting cognitive deficits in Parkinson's disease
(PD) revealed impairment in a variety of tasks related to memory, learning, and
attention. One ubiquitous task that has not received much attention, is
categorization system-switching. Categorization system-switching is a form of
task-switching requiring participants to switch between different categorization
systems. In this article, we explore whether older adults and people with PD show
deficits in categorization system-switching. METHOD: Twenty older adults
diagnosed with PD, 20 neurologically intact older adults, and 67 young adults
participated in this study. Participants were first trained in rule-based (RB)
and later information-integration (II) categorization separately. After training
on the tasks, participants performed a block of trial-by-trial switching where
the RB and II trials were randomly intermixed. Finally, the last block of trials
also intermixed RB and II trials were randomly but additionally changed the
location of the response buttons. RESULTS: Contrary to our hypothesis, the
results show no difference in accuracy between older adults and people with PD
during the intermixed trial block, as well as no difference in response time (RT)
switch cost. However, both groups were less accurate during intermixed trial
blocks and had a higher RT switch cost when compared with young adults. In
addition, the proportion of participants able to switch systems was smaller in
people with PD than in young adults. CONCLUSIONS: The results suggest that older
adults and people with PD have impaired categorization system-switching ability,
and that this ability may be related to a decrease in tonic dopamine (DA) levels
associated with normal aging and PD. (PsycINFO Database Record
PMID- 29952587
TI - A new and unique prediction for cue-search in a parallel-constraint satisfaction
network model: The attraction search effect.
AB - A common assumption of many established models for decision making is that
information is searched according to some prespecified search rule. While the
content of the information influences the termination of search, usually
specified as a stopping rule, the direction of search is viewed as being
independent of the valence of the retrieved information. We propose an extension
to the parallel constraint satisfaction network model (iCodes: integrated
coherence-based decision and search), which assumes-in contrast to prespecified
search rules-that the valence of available information influences search of
concealed information. Specifically, the model predicts an attraction search
effect in that information search is directed toward the more attractive
alternative given the available information. In 3 studies with participants
choosing between two options based on partially revealed probabilistic
information, the attraction search effect was consistently observed for
environments with varying costs for information search although the magnitude of
the effect decreased with decreasing monetary search costs. We also find the
effect in reanalyses of 5 published studies. With iCodes, we propose a fully
specified formal model and discuss implications for theory development within
competing modeling frameworks. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29952588
TI - Animal pointing: Changing trends and findings from 30 years of research.
AB - The past 30 years have witnessed a continued and growing interest in the
production and comprehension of manual pointing gestures in nonhuman animals.
Captive primates with diverse rearing histories have shown evidence of both
pointing production and comprehension, though there certainly are individual and
species differences, as well as substantive critiques of how to interpret
pointing or "pointing-like" gestures in animals. Early literature primarily
addressed basic questions about whether captive apes point, understand pointing,
and use the gesture in a way that communicates intent (declarative) rather than
motivational states (imperative). Interest in these questions continues, but more
recently there has been a dramatic increase in the number of articles examining
pointing in a diverse array of species, with an especially large literature on
canids. This proliferation of research on pointing and the diversification of
species studied has brought new and exciting questions about the evolution of
social cognition, and the effects of rearing history and domestication on
pointing production and, more prolifically, comprehension. A review of this work
is in order. In this article, we examine trends in the literature on pointing in
nonhumans. Specifically, we examine publication frequencies of different study
species from 1987 to 2016. We also review data on the form and function of
pointing, and evidence either supporting or refuting the conclusion that various
nonhuman species comprehend the meaning of pointing gestures. (PsycINFO Database
Record
PMID- 29952589
TI - Measurement invariance of the DSM-5 Section III pathological personality trait
model across sex.
AB - The dimensional pathological personality trait model proposed in the Diagnostic
and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5), Section III
Criterion B, has shown promising results for its validity and utility in
conceptualizing personality pathology. However, as its structural equivalence
across sex is yet to be tested, the validity for the model across males and
females remains uncertain. In the present article, we examined sex measurement
invariance of the DSM-5 trait model in a large undergraduate sample using the
Personality Inventory for DSM-5. A series of confirmatory and exploratory factor
analyses suggested that, although the exact facet-domain relationships as
specified in the DSM-5 were not observed, the facets generally organize into a
model with five latent factors similar to those listed in the DSM-5 Section III
Criterion B. Further, these five factors were fully measurement invariant across
sex at the configural, metric, and scalar levels. Examination of the latent trait
mean levels suggests that females tend to have higher scores on latent Negative
Affectivity, whereas males tend to have higher scores on latent Antagonism,
Detachment, Psychoticism, and Disinhibition. These results indicate that the DSM
5 Section III pathological personality trait model is fully structurally
equivalent across sex, a property that is lacking in the traditional categorical
model in Section II. This further validates the use of the dimensional DSM-5
trait model for personality disorder assessment and conceptualization in both
research and clinical settings. (PsycINFO Database Record
PMID- 29952590
TI - Stigma of psychosis: Do diagnostic label, symptom manifestation, and gender
matter?
AB - The present study examined the effects of psychiatric label (thought and
perceptual dysregulation vs. schizophrenia), symptom manifestation (positive vs.
negative symptoms), and gender (male vs. female) of a vignette character with
psychosis on the general public's cognitive attributions, affective reactions,
and behavioral responses. A 2 * 2 * 2 vignette-based telephone survey was
conducted based on 533 Chinese adults from 18 to 60 years of age. Hierarchical
regression analysis revealed that compared with the label of thought and
perceptual dysregulation, the public accorded the label of schizophrenia with
greater levels of intentionality and controllability. A male character predicted
greater intentionality, controllability, and social rejection than did a female
character. Positive symptoms predicted greater controllability, contempt, and
social rejection than did negative symptoms. Theoretical and practical
implications on the findings were discussed. (PsycINFO Database Record
PMID- 29952591
TI - An evaluation of the predictive validity of the SAVRY and YLS/CMI in justice
involved youth with fetal alcohol spectrum disorder.
AB - Despite the high prevalence of fetal alcohol spectrum disorder (FASD) in youth
criminal justice settings, there is currently no research supporting the use of
violence risk assessment tools in this population. This study examined the
predictive validity of the Structured Assessment of Violence Risk in Youth
(SAVRY) and the Youth Level of Service/Case Management Inventory (YLS/CMI) in
justice-involved youth with FASD. Participants were 100 justice-involved youth
(ages 12-23; 81% male), including 50 diagnosed with FASD and 50 without FASD or
prenatal alcohol exposure. The SAVRY and YLS/CMI were prospectively coded based
on interview and file review, with recidivism (both any and violent specifically)
coded 1-year post-baseline assessment. Results provide preliminary support for
the validity of the SAVRY and YLS/CMI in predicting recidivism in justice
involved youth with FASD. Higher ratings across SAVRY and YLS/CMI domains were
found in youth with FASD, underscoring a critical need for assessments and
interventions to buffer recidivism risk and address clinical needs. (PsycINFO
Database Record (c) 2018 APA, all rights reserved).
PMID- 29952592
TI - Development and validation of a State-Reappraisal Inventory (SRI).
AB - Reappraisal is a multifaceted construct associated with a wide range of proximal
(e.g., affective responses) and distal (e.g., psychopathology) consequences. To
date, our understanding of use of reappraisal is based either on self-reports of
tendencies to use a specific strategy in general or in the last week or on
performance on lab-based tasks. There has been little effort to measure use of
reappraisal immediately following an emotionally evocative situation (i.e., state
reappraisal). To close this gap, we developed the State-Reappraisal Inventory
(SRI) that ascertains use of reappraisal immediately after an emotional event. In
Study 1, exploratory factor analyses yielded two reliable subscales measuring
state levels of construal of an emotion-eliciting situating as more positive
(Increase Positive) and less negative (Decrease Negative). In two further
studies, confirmatory factor analyses using a bifactor model provided a good fit
for the data and surpassed three competing models. In a fourth study, the SRI
showed sensitivity to experimentally induced state changes in reappraisal. Across
studies, the questionnaire demonstrated good convergent and discriminant
validity. Thus, the SRI is a new measure of state-reappraisal that can allow
researchers and clinicians to examine the extent to which individuals use
reappraisal in emotional situations. (PsycINFO Database Record (c) 2018 APA, all
rights reserved).
PMID- 29952593
TI - The reliability and predictive validity of the Guidelines for Stalking Assessment
and Management (SAM).
AB - This study assessed the reliability and validity of the Guidelines for Stalking
Assessment and Management (SAM), a structured professional judgment measure for
assessing stalking risks. The SAM was completed retrospectively from file review
for 146 adult stalkers (90.4% male) referred to a community-based forensic mental
health service. Interrater reliability (IRR) was initially poor, but developing a
strict definition of stalking currency and rescoring the SAM led to improvement.
Based on the updated scoring, IRR was moderate for judgments about whether
stalking was ongoing at the time of assessment, and fair to moderate for summary
risk judgments. Both case prioritization (area under the curve [AUC] = .69) and
risk for continued stalking (AUC = .76) ratings discriminated between groups,
with high-risk stalkers 5-9 times as likely as low-risk stalkers to reoffend by
stalking their original victims. Lifetime SAM total scores (AUC = .70) also
featured moderate to good discrimination. Follow-up analyses suggested that this
was driven mainly by the recent presence of risk markers and the nature of any
ongoing stalking situation rather than historical or individual factors. Findings
support the use of the SAM to structure risk judgments made by those with
experience in assessing stalking. Current results also imply that IRR might be
improved by introducing (a) a fixed definition of stalking currency and (b) usage
guidelines for specific contexts. (PsycINFO Database Record (c) 2018 APA, all
rights reserved).
PMID- 29952594
TI - A meta-analysis of the five-factor internal structure of the Personality
Inventory for DSM-5.
AB - The Alternative Model for Personality Disorders (AMPD) in the Diagnostic and
Statistical Manual of Mental Disorders, fifth edition, Section III, presents a
new approach to conceptualizing personality psychopathology and diagnosing
personality disorders. The Personality Inventory for DSM-5 (PID-5) was designed
to measure Criterion B of the AMPD and is composed of 25 lower-order facet trait
scales that form 5 higher-order domain trait scales. Although the PID-5 has
mostly adequate to strong psychometric qualities, the lower-order factor
structure of PID-5 facet scales has shown considerable variability across
studies, and several PID-5 facets scales show evidence of interstitiality-the
cross-loading of facets onto more than 1 domain. This interstitiality is neither
unexpected nor especially problematic because complex models of personality have
traits that are by nature interstitial. What is problematic, however, is that the
factor loadings of these interstitial facets vary across samples, suggesting that
some PID-5 facet scales are likely susceptible to sampling error and sampling
variability. Moreover, the magnitude of some cross-loadings in some studies is
substantive (i.e., >= .30). The objective of the current study was to conduct a
meta-analysis of the internal structure of the PID-5 to offset potential
variability associated with sampling error and gain a clearer picture of the
lower-order structure of PID-5 facet scales. This was accomplished using weighted
mean factor loadings of the PID-5 facet scales across 14 independent samples (N =
14,743). Results supported that the level of interstitiality decreased when
multiple samples were combined, and a clearer picture of the internal structure
of the PID-5 facet scales emerged. (PsycINFO Database Record
PMID- 29952595
TI - Test-retest reliability and practice effects of a computerized neuropsychological
battery: A solution-oriented approach.
AB - This study examined test-retest reliabilities and (predictors of) practice
effects of the widely used computerized neuropsychological battery CNS Vital
Signs. The sample consisted of 158 Dutch healthy adults. At 3 and 12 months
follow-up, 131 and 77 participants were retested. Results revealed low to high
test-retest reliability coefficients for CNS VS' test and domain scores.
Participants scored significantly higher on the domains of Cognitive Flexibility,
Processing Speed, and Reaction Time at the 3-month retest. No significant
differences in performance were found over the second interval. Age, education,
and retest-interval were not significantly associated with practice effects.
These results highlight the need for methods that evaluate performance over time
while accounting for imperfect test-retest reliabilities and practice effects. We
provided RCI-formulae for determining reliable change, which may be possible
solution for future work facing the methodological issues of retesting. (PsycINFO
Database Record (c) 2018 APA, all rights reserved).
PMID- 29952596
TI - The D-KEFS Trails as performance validity tests.
AB - This study was designed to examine the potential of the Delis-Kaplan Executive
System (D-KEFS) version of the Trail Making Test (TMT) as a performance validity
test (PVT). Data were collected from a mixed clinical sample of 157 consecutively
referred outpatients (49% male, MAge = 47.1, MEducation = 13.6) undergoing
neuropsychological assessment at an academic medical center in the northeastern
United States. Sensitivity and specificity of the D-KEFS Trails to
psychometrically defined invalid responding was calculated across various cutoffs
and criterion PVTs. The D-KEFS Trails produced classification accuracy comparable
to the original version of the TMT, hovering around the "Larrabee limit" (.50
sensitivity at .90 specificity). Different cutoffs (age-corrected scaled score
<=5 on Trails 1-3, <=4 on Trails 4 and <=8 on Trails 5) were needed to achieve
the same classification accuracy across the five trials. Combining multiple
cutoffs improved the signal detection performance. The study provides preliminary
evidence of the utility of D-KEFS Trails as a PVT. Embedded PVTs are valuable,
because they make a multivariate approach to validity assessment feasible.
Combining validity indicators is superior to relying on single cutoffs. (PsycINFO
Database Record
PMID- 29952597
TI - Early bird fails the PVT? The effects of timing artifacts on performance validity
tests.
AB - This study was designed to investigate the effects of timing on the likelihood of
failing the Recognition Memory Test-Words (RMT) and Word Choice Test (WCT). The
RMT and WCT were administered in counterbalanced order either at the beginning
(Time 1) or at the end (Time 2) of a test battery to a mixed clinical sample of
196 patients (Mage = 44.5 years, 55.1% female) medically referred for
neuropsychological evaluation. The risk of failing the accuracy score was higher
at Time 1 on both the RMT (relative risk [RR]: 1.44-1.64) and the WCT (RR: 1.21
1.50) across a range of cutoffs. Likewise, the risk of failing the time-to
completion score was higher at Time 1 on both the RMT (RR: 1.30-1.94) and the WCT
(RR: 1.58-3.75). Established cutoffs failed to reach specificity standards at
Time 1; more liberal cutoffs cleared specificity thresholds at Time 2. According
to our findings, the RMT and WCT may be prone to false-positive errors at Time 1.
Conversely, when administered at Time 2, existing cutoffs may have lower
sensitivity, but they are highly specific to invalid performance. Timing should
be considered during both test selection and the interpretation of RMT and WCT
scores. Using conservative cutoffs for morning administrations and liberal
cutoffs for afternoon administrations may be necessary to neutralize timing
artifacts. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
PMID- 29952598
TI - Borderline personality disorder is equally trait-like and state-like over ten
years in adult psychiatric patients.
AB - Borderline personality disorder (PD) has historically been cast as an unabating
condition. Longitudinal data, however, support a more variable time course marked
by remission and relapse. In the present study, we tested the possibility that
borderline PD has both stable (i.e., consistently present across time and
situation, as modern diagnostic systems stipulate) and dynamic (i.e., episodic
and situational) elements. Participants were 668 patients from the Collaborative
Longitudinal Personality Disorders Study who were administered semistructured
diagnostic interviews 5 times over a decade. Trait-state-occasion modeling
dissected borderline pathology into time-invariant (i.e., trait) and time-varying
(i.e., state) components. Contradicting traditional views of PD intransigence,
less than half of borderline PD variability (approximately 45%) was time
invariant (i.e., perfectly stable) over the study timeframe. Furthermore, we
found that the time-invariant component of borderline pathology, which we termed
borderline proneness, was very closely related (r = .81) to a previously
validated Five Factor Model trait composite of borderline features. Moreover, the
trait versus state components showed a clear pattern of discriminant validity in
relation to several putative causal agents for borderline PD (i.e., environmental
pathogens, temperament dimensions). We conclude that borderline pathology
contains a stable core and sizable situational components, and that both elements
relate systematically to normative personality dimensions and known risk factors.
These findings have key implications for etiological research, prognosis, and
treatment for borderline PD. (PsycINFO Database Record
PMID- 29952599
TI - Age variations in cohort differences in the United States: Older adults report
fewer constraints nowadays than those 18 years ago, but mastery beliefs are
diminished among younger adults.
AB - Life Span psychological and life course sociological perspectives have long
acknowledged that individual functioning is shaped by historical and
sociocultural contexts. Secular increases favoring later-born cohorts are widely
documented for fluid cognitive performance and well-being (among older adults).
However, little is known about secular trends in other key resources of
psychosocial function such as perceptions of control and whether historical
changes have occurred in young, middle-aged, and older adults alike. To examine
these questions, we compared data from two independent national samples of the
Midlife in the United States survey obtained 18 years apart (1995/96 vs. 2013/14)
and identified case-matched cohorts (per cohort, n = 2,223, aged = 23-75 years)
based on age and gender. We additionally examined the role of economic resources
for cohort differences in perceived mastery and constraints. Results revealed
that older adults in later-born cohorts reported perceiving fewer constraints
than did matched controls 18 years ago, with such positive secular trends being
particularly pronounced among women. In contrast, younger adults reported
perceiving more constraints in later-born cohorts than those 18 years ago and
also reported perceiving lower mastery. We conclude from our national U.S. sample
that secular trends generalize to central psychosocial resources across
adulthood, such as perceptions of control, but are not unanimously positive. We
discuss possible underlying mechanisms and practical implications. (PsycINFO
Database Record
PMID- 29952600
TI - Speech categorization develops slowly through adolescence.
AB - The development of the ability to categorize speech sounds is often viewed as
occurring primarily during infancy via perceptual learning mechanisms. However, a
number of studies suggest that even after infancy, children's categories become
more categorical and well defined through about age 12. We investigated the
cognitive changes that may be responsible for such development using a visual
world paradigm experiment based on (McMurray, Tanenhaus, & Aslin, 2002). Children
from 3 age groups (7-8, 12-13, and 17-18 years) heard a token from either a b/p
or s/? continua spanning 2 words (beach/peach, ship/sip) and selected its
referent from a screen containing 4 pictures of potential lexical candidates. Eye
movements to each object were monitored as a measure of how strongly children
were committing to each candidate as perception unfolds in real-time. Results
showed an ongoing sharpening of speech categories through 18, which was
particularly apparent during the early stages of real-time perception. When
analysis targeted to specifically within-category sensitivity to continuous
detail, children exhibited increasingly gradient categories over development,
suggesting that increasing sensitivity to fine-grained detail in the signal
enables these more discrete categorizations. Together these suggest that speech
development is a protracted process in which children's increasing sensitivity to
within-category detail in the signal enables increasingly sharp phonetic
categories. (PsycINFO Database Record
PMID- 29952601
TI - The development of intergroup resource allocation: The role of cooperative and
competitive in-group norms.
AB - The present study investigated age-related changes in the intergroup allocation
of resources depending on whether the ingroup norm was competitive or
cooperative. Participants included children (Mage = 8.69), adolescents (Mage =
13.81), and adults (Mage = 20.89), (N = 263) who were inducted into simulated
groups and informed about an ingroup norm of either cooperation or competition.
The goal context for the resource allocation task was either prosocial (to
benefit the welfare of animals in a charity event) or group focused (to win a
national interschool competition). They were then asked to allocate resources
between an ingroup and outgroup, and to justify their allocation. The findings
showed that children allocated significantly more resources to their ingroup in
order to achieve a prosocial goal, but only when the ingroup norm was
competitive. In contrast, adolescents and adults allocated resources equally
irrespective of the ingroup norm. These findings showed that children prioritized
the moral goal of welfare over that of fairness when their ingroup favored
competition, while adolescents and adults always prioritized fairness. Older
participants justified their equal allocation with greater reference to the
importance of fair competition. This study demonstrated an important
developmental shift in how the prioritization of moral goals during intergroup
resource allocation is influenced by ingroup norms of competition and
cooperation. (PsycINFO Database Record
PMID- 29952602
TI - Growth patterns of future orientation among maltreated youth: A prospective
examination of the emergence of resilience.
AB - During adolescence, a positive outlook toward the future (i.e., future
orientation) can protect youth from the risks conferred by childhood adversity.
Research to date, however, has largely considered future orientation as a static
attribute. Developmental systems perspectives suggest that future orientation,
when considered across time, will exhibit dynamic trajectories with levels
changing in response to the varying balance of risks and resources in youths'
environments. Investigating the developmental course and consequences of future
orientation is particularly germane to maltreated youth who may benefit from
programs that target this protective mechanism. The present study tested
hypotheses regarding the developmental course of future orientation, including
the association of distinct future orientation trajectories with time-varying
risk factors and resources, and the association of continuity and change in
future orientation trajectories with young adult psychosocial functioning.
Hypotheses were investigated with longitudinal (T1 Mage = 12.22, T2 Mage = 13.52,
T3 Mage = 14.79, T4 Mage = 18.54), multireporter data from a nationally
representative sample of maltreated youth (N = 1,461). Growth mixture modeling
(GMM) identified three classes of growth trajectories in future orientation: high
persistent, low start/increasing, and high start/decreasing. Time-variant and
invariant risk factors and resources differentiated youths' future orientation
trajectories. Youth in the high-persistent and low start/increasing trajectories
were more likely to attain young adulthood developmental milestones-including
independent living skills, social capital, employment, and higher weekly income.
This study documents how an important component of resilient adaptation emerges
and promotes positive outcomes among highly vulnerable youth. (PsycINFO Database
Record
PMID- 29952603
TI - On the positive relationship between breastfeeding & intelligence.
AB - A wealth of literature has examined the association between breastfeeding and the
development of cognitive abilities in childhood. In particular, at least some
evidence exists suggesting that breastfed children perform better on measures of
intelligence later in life. Although a correlation appears to be present, fewer
observational studies have included appropriate adjustment for potentially
confounding variables; maternal intelligence, maternal education, and cognitive
stimulation provided by mothers being chief among them. As a result, we analyze a
national sample of approximately 790 American respondents to test the association
between breastfeeding and intelligence during childhood and adolescence using
multiple intelligence tests and controlling for a range of key covariates. Our
results suggest that the correlation between breastfeeding throughout the first
six months of life and intelligence is statistically significant and consistent,
yet of substantively minor impact. (PsycINFO Database Record
PMID- 29952604
TI - Timing of cyclic estradiol treatment differentially affects cognition in aged
female rhesus monkeys.
AB - Some evidence suggests that there may be a limited "window of opportunity" for
beneficial effects of hormone therapy after menopause in women. We tested whether
the timing of cyclic estradiol (E2) treatment impacted its effect on cognitive
function in aged, surgically menopausal (ovariectomized) rhesus monkeys. Monkeys
were assigned to one of four treatment conditions after ovariectomy: either
vehicle or E2 treatment for the duration of the protocol, vehicle for the first 2
years of the protocol followed by E2 for the remainder (delayed treatment), or E2
for the first 11 months of the protocol followed by vehicle for the remainder
(withdrawn treatment). Delayed treatment addressed the hypothesis that E2
treatment initiated more than 2 years postovariectomy would have a reduced effect
on cognitive function. Withdrawn treatment mirrored current clinical advice to
women to use hormone therapy in the initial postmenopausal period then
discontinue it. Two periods of cognitive testing assessed treatment effects on
cognition over time. E2 treatment predominantly affected a prefrontal cortex
dependent test of spatiotemporal working memory (delayed response). Monkeys with
delayed E2 treatment modestly improved in delayed response performance over time,
whereas vehicle-treated monkeys declined. Monkeys with withdrawn E2 treatment
maintained their performance across assessments, as did monkeys treated with E2
across the entire protocol. These findings suggest that a "window of opportunity"
for hormone treatment after cessation of ovarian function, if present in nonhuman
primates, lasts longer than 2 years. They also support the notion that beneficial
effects of hormone therapy may persist after discontinuation of treatment.
(PsycINFO Database Record
PMID- 29952605
TI - Orexin neurons couple neural systems mediating fluid balance with motivation
related circuits.
AB - During extracellular dehydration, neural systems that sense deficits in body
fluid homeostasis operate in tandem with those that mediate motivation and reward
in order to promote ingestive behaviors that restore fluid balance. We
hypothesized that hypothalamic orexin (Ox) neurons act as an interface to couple
brain regions sensing and processing information about body fluid status with
central nervous system motivation and reward systems. An initial set of
anterograde and retrograde tracing experiments suggested that structures along
the lamina terminalis (LT), a region of the forebrain that serves to monitor and
integrate information reflecting body fluid balance, project to hypothalamic Ox
neurons that, in turn, project to dopamine neurons in the ventral tegmental area
(VTA). A second set of experiments determined whether Ox neuron activation is
associated with extracellular dehydration and the seeking out and consumption of
water and saline. An elevation of Fos-like immunoreactivity in Ox neurons was
observed in fluid-depleted rats that were allowed to ingest water and sodium. A
final experiment was conducted to determine whether Ox release in the VTA
promotes thirst and salt appetite. Bilateral microinjection of the Ox Type I
receptor antagonist SB-408124 into the VTA prior to acute extracellular
dehydration attenuated fluid intake. Together, these studies support the
hypothesis that structures along the LT modulate activity in the VTA through
actions of orexinergic neurons that have cell bodies in the hypothalamus. This
pathway may function to facilitate sustained consumption of fluids necessary for
restoration of fluid balance. (PsycINFO Database Record
PMID- 29952607
TI - Pigeons consistently prefer easy over harder access to food: No reversal after
direct dopaminergic stimulation.
AB - Many studies show that animals may prefer earned over free food-a phenomenon
referred to as "contrafreeloading." In rodents, dopamine-which is involved in
incentive motivation and effort-facilitates the occurrence of such a preference.
Here, we investigated the behavioral effects of pramipexole (PPX), a dopamine
D2/3 receptor agonist, on contrafreeloading in pigeons. In Experiment 1, 2 groups
of pigeons (PPX and SAL) were simultaneously exposed to a bowl that contained
grains only (easy food option) and a bowl that contained grains covered with
sawdust (harder food option) for 6 sessions. They were tested in two treatment
conditions (high vs. low amount of food available). In Experiment 2, the two
groups of pigeons were first repeatedly presented with the harder food option
(training phase, 6 sessions) and then with the two options at the same time (test
phase, 3 sessions). In order to potentially increase the physiological effects of
PPX, the dose was tripled, and there was a 2-week incubation of the drug between
Sessions 3 and 4 at training. The results indicate that the pigeons from both
groups preferred to forage on the easy food option, and PPX did not alter this
preference. Despite indications that PPX was effective, its action consisted of
reducing-rather than magnifying-the attractiveness of the harder food option. It
is suggested that pigeons are less motivated to deploy foraging effort than
rodents in similar tasks. (PsycINFO Database Record
PMID- 29952606
TI - Estradiol treatment in a nonhuman primate model of menopause preserves affective
reactivity.
AB - Human affective life changes with age, becoming more positive and less negative
in later life. This change occurs even as aging leads to declines in health and
cognitive outcomes. Despite these well-documented effects in humans, the extent
to which affective processes change as a result of aging in nonhuman animals,
particularly nonhuman primates, is unclear. As a first step toward developing an
animal model for human affective aging, we tested aged, surgically menopausal
aged and middle-aged gonadally intact female rhesus monkeys (Macaca mulatta) on a
classic index of affective reactivity in monkeys, the Human Intruder Task. The
Human Intruder Task evaluates behavioral responses to varying levels of threat.
Aged, surgically menopausal monkeys received hormone replacement therapy
consisting of a cyclic estradiol regimen or vehicle injections as a control.
Average responsivity to threat did not vary by condition, but middle-aged monkeys
and aged monkeys on estradiol were more reactive to the most potent level of
threat than to a moderate level of threat, replicating previously published
results in other age groups and male monkeys. In contrast, aged monkeys who were
not on estradiol did not show such calibration to threat level. These findings
suggest that estrogen may be important for maintaining more youthful affective
responding. They also illustrate the utility of behavioral assays of affective
reactivity in nonhuman primate models of cognitive and reproductive aging in
humans. (PsycINFO Database Record
PMID- 29952609
TI - Sex-based differences in affective and cognitive empathy following severe
traumatic brain injury.
AB - OBJECTIVE: To examine sex differences in self-ratings for affective and cognitive
empathy for males and females with traumatic brain injury (TBI) and compare these
to observer ratings. METHOD: Self and observer (e.g., spouse) ratings of
affective and cognitive empathy were obtained for 160 participants (116 males)
with severe TBI, using the Interpersonal Reactivity Index Empathic Concern (EC)
and Perspective Taking (PT) subscales, respectively. RESULTS: When compared to
sex norms, female self-ratings were significantly lower for both subscales,
whereas men's self-report ratings were only lower for PT. For EC, more women
(44%) were found to be substantially below the normative means (>=2 SDs) than men
(17%), p < .001. When comparing women and men with TBI, self-report and observer
ratings indicated both sexes had similar empathy levels (both subscales). Self
versus observer ratings showed that women's self-ratings were significantly
higher than observer's ratings on PT (p < .001); men's self-ratings were
significantly higher than observer's ratings on PT (p < .001) and EC (p = .009).
CONCLUSIONS: In contrast to the typically observed superior female empathy, this
study suggests this advantage may disappear after a TBI, and possibly result in a
disadvantage compared to their uninjured female peers. Theoretical implications
of self-awareness and cultural gender expectations for empathy are discussed.
(PsycINFO Database Record
PMID- 29952610
TI - Preliminary evidence for differential trajectories of recovery for cognitive
flexibility following sports-related concussion.
AB - OBJECTIVE: A critical barrier to the understanding of disruptions to cognitive
flexibility following sports-related concussion is the use of assessments that
conflate shifts of visuospatial attention and contextual rules. Because these
dissociable forms of cognitive flexibility are subserved by distinct neural
networks, the utility of a cognitive flexibility assessment following concussion
may be reduced, depending upon the extent to which the task requires shifting
visuospatial attention relative to shifting contextual rules. Accordingly, the
current investigation examined the extent to which these aspects of cognitive
flexibility exhibit differential trajectories of recovery following a sports
related concussion. METHOD: Twenty-two athletes with sports-related concussions
were assessed on a cognitive flexibility task with 2 switch conditions (i.e.,
perceptual-based and contextual rule-based) within 72 hr of injury, after return
to play, and within 1 month following return to play. Thirty-three healthy
control athletes were tested at the same intervals. RESULTS: Findings revealed
that concussed athletes demonstrated protracted disruptions in task performance
on a visuospatial attention-based cognitive flexibility task relative to healthy
controls, whereas disruptions in task performance on a contextual rule-based
cognitive flexibility task resolved after the acute phase of injury. These
findings suggest that dissociable forms of cognitive flexibility exhibit
differential trajectories of recovery. CONCLUSIONS: Therefore, evaluations
detecting sports-related concussion disruptions in cognitive flexibility may be
reduced depending on the extent to which they rely on contextual rule-based
decisions. Test batteries focusing on visuospatial attention-based demands may be
useful additions to aid in the objective assessment and follow-up management of
athletes following the acute phase of injury. (PsycINFO Database Record
PMID- 29952608
TI - Effects of light at night on laboratory animals and research outcomes.
AB - Light has substantial influences on the physiology and behavior of most
laboratory animals. As such, lighting conditions within animal rooms are
potentially significant and often underappreciated variables within experiments.
Disruption of the light/dark cycle, primarily by exposing animals to light at
night (LAN), disturbs biological rhythms and has widespread physiological
consequences because of mechanisms such as melatonin suppression, sympathetic
stimulation, and altered circadian clock gene expression. Thus, attention to the
lighting environment of laboratory animals and maintaining consistency of a
light/dark cycle is imperative for study reproducibility. Light intensity, as
well as wavelength, photoperiod, and timing, are all important variables.
Although modern rodent facilities are designed to facilitate appropriate light
cycling, there are simple ways to modify rooms to prevent extraneous light
exposure during the dark period. Attention to lighting conditions of laboratory
animals by both researchers and research care staff ensures best practices for
maintaining animal welfare, as well as reproducibility of research results.
(PsycINFO Database Record
PMID- 29952611
TI - Time-based prospective memory in children and adolescents with traumatic brain
injury: Impact of working memory demands.
AB - OBJECTIVE: Difficulties with prospective memory are frequently reported following
pediatric traumatic brain injury (TBI), but rarely researched. We aimed to (i)
investigate time-based prospective memory post-pediatric TBI; (ii) examine
whether time-based prospective memory is differentially impacted by the demand
placed on working memory; and (iii) explore which components of working memory
(viz., central executive, phonological loop, and visuospatial sketchpad) are
involved in time-based prospective memory under low and high cognitive load
following pediatric TBI. METHOD: Thirty-nine children and adolescents (20
survivors of moderate-severe TBI and 19 healthy controls) completed (i) a newly
developed time-based prospective memory task (TBPMT), embedded in an ongoing
lexical-decision task, with two conditions: low and high working memory load; and
(ii) tests of working memory components from the Automated Working Memory
Assessment. RESULTS: Compared to controls, participants with TBI had
significantly lower prospective memory accuracy on the TBPMT across working
memory loads (low, high). In contrast, the groups did not differ in time
monitoring or accuracy on the ongoing task. In the TBI group, higher scores on
tests of the central executive (but not phonological loop or visuospatial
sketchpad) were associated with higher prospective memory accuracy and time
monitoring (controlling for age). CONCLUSIONS: Time-based prospective memory is
impaired following moderate-severe pediatric TBI, irrespective of the level of
working memory demand. Our findings suggest that children and adolescents with
TBI may be at risk of failing to perform future intentions at the right time in
daily life, especially for individuals identified as having deficits in central
executive functioning. (PsycINFO Database Record
PMID- 29952612
TI - Computerized attentional training and transfer with virtual reality: Effect of
age and training type.
AB - OBJECTIVE: The aims of this study were to assess whether computerized attentional
training improves dual-tasking abilities in older adults and whether its effect
and transfer are modulated by age and the type of training provided. This study
also used virtual reality (VR) as a proxy to measure transfer in a real life
related context. METHOD: Sixty participants (30 older and 30 younger adults) were
randomized to either: (a) single-task training (two tasks practiced in focused
attention; visual detection and alphanumeric equation task); or (b) divided
attention variable-priority training (varying the amount of attention to put on
each task when performed concurrently). Training effects were assessed at pre-
and post-training with tasks similar to the one used in training. Transfer was
measured with the virtual car ride, an immersive dual-task scenario and a self
reported questionnaire. RESULTS: In older adults, variable-priority improved
attentional control abilities and led to better transfer in the VR dual-task
scenario compared with single-task. Younger adults benefited equally from the two
types of training and transfer was found on the Alpha span task when performed
concurrently in VR. Single-task improved the ability of all participants to carry
out the tasks in the focused attention condition. No transfer effects were found
on the self-reported measure for either training type or age. CONCLUSION:
Attention remains plastic in old age and programs designed to improve attentional
control might be beneficial to older adults. Importantly, training can produce
transfer to more real life related tasks and transfer remains possible throughout
the life span. (PsycINFO Database Record
PMID- 29952613
TI - An eight-week mindfulness-based stress reduction (MBSR) workshop increases
regulatory choice flexibility.
AB - Individuals encounter a variety of emotional challenges daily, with optimal
emotion modulation requiring adaptive choice among available means of regulation.
However, individuals differ in the ability to flexibly and adaptively move
between engaging and disengaging emotion regulation (ER) strategies as per
contextual demands, referred to as regulatory choice flexibility. Greater
regulatory choice flexibility is associated with greater mental health, well
being and resilience, warranting the development of interventions to increase
such flexibility. We hypothesized that a mindfulness-based stress reduction
(MBSR) program would fulfill this goal. To test our hypothesis, we recruited
college students to either participate in an 8-week MBSR workshop or join a
waiting list for a later workshop (i.e., control participants). After the
workshop's completion, all participants were invited to the laboratory and
completed several computerized tasks examining their regulatory choice
flexibility when exposed to universally emotion-laden stimuli as well as stimuli
specifically related to the students' social and political environment. The
regulatory choice patterns of participants who underwent MBSR training were found
to be more flexible than those of participants who had not yet completed the
workshop, with the former more likely than the latter to favor an engaging ER
strategy (i.e., reappraisal) when faced with low-intensity stimuli and a
disengaging strategy (i.e., distraction) when faced with high-intensity stimuli.
The findings' importance is discussed. (PsycINFO Database Record
PMID- 29952614
TI - "Prospective relations between parent-adolescent acculturation conflict and
mental health symptoms among Vietnamese American adolescents" Correction to
Nguyen et al. (2018).
AB - : Reports an error in "Prospective relations between parent-adolescent
acculturation conflict and mental health symptoms among Vietnamese American
adolescents" by Diem Julie Nguyen, Joanna J. Kim, Bahr Weiss, Victoria Ngo and
Anna S. Lau (Cultural Diversity and Ethnic Minority Psychology, 2018[Apr], Vol
24[2], 151-161). In the article, the wrong figure was published for Figure 1.
Figure 1 should have shown externalizing models. The correct Figure is provided
in the erratum. (The following abstract of the original article appeared in
record 2017-30936-001.) Objectives: Intergenerational acculturation conflict in
immigrant families has been implicated as a risk factor for adolescent
maladjustment. However, the directionality and specific family related mediators
of this association have not been identified. The present study prospectively
examined relations between adolescent reports of perceived acculturation conflict
and internalizing and externalizing mental health symptoms. Perceived parent
adolescent relationship strain and perceived parental psychological control were
examined as potential mediators. METHOD: Survey measures were administered to 375
Vietnamese American adolescents (48.8% males; M = 15.55 years, SD = .59) at 3
time points over 6 months. RESULTS: Using cross-lagged path analysis, perceived
acculturation conflict predicted externalizing symptoms, whereas internalizing
symptoms predicted perceived acculturation conflict. Perceived maternal
psychological control mediated the association between perceived acculturation
conflict and later externalizing symptoms, whereas maternal psychological
control, parental unresponsiveness, and unmet parent expectations mediated the
association between internalizing symptoms and later acculturation conflict.
CONCLUSION: Culturally competent enhancement of parental sensitivity and
responsiveness might be targeted as a modifiable protective factor in family
based preventive interventions for at-risk immigrant families. (PsycINFO Database
Record
PMID- 29952616
TI - Is ADHD, independent of ODD, associated with whether and why college students
misuse stimulant medication?
AB - Although previous research suggests that undergraduates with untreated or
undertreated attention-deficit/hyperactivity disorder (ADHD) symptoms may have
academic motives for stimulant medication misuse, no previous work has examined
the relation of ADHD symptoms, controlling for comorbid oppositional defiant
disorder (ODD), to misuse, or has explored how these symptoms are differentially
related to motives for misuse. Among a sample of 900 students from one public
university, the current study first tested whether increased ADHD symptomology
(using the Current Symptoms Scale, CSS) was associated with an increased
likelihood of misusing stimulant medication, controlling for comorbid ODD. We
then examined whether those with increased ADHD symptomology were more likely to
report academic motives for misuse. The prevalence rate of misuse in the past
year was 22%. Participants who met symptom count criteria for ADHD (controlling
for comorbid ODD) were 2.90 times more likely to misuse stimulant medication than
those who did not. Among misusers, those who met ADHD criteria were also 2.80
times more likely to report academic motives for misuse. These results support
that stimulant medication misuse is likely driven, in part, by inadequate or
absent care for the executive functioning impairments associated with ADHD.
Therefore, a greater focus on assessment and treatment of college students with
ADHD symptoms is warranted. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29952617
TI - Deviance regulation theory and drinking outcomes among Greek-life students during
spring break.
AB - Alcohol use among college students increases during spring break, which often
results in more alcohol-related consequences. Given the rates of heavy alcohol
use among Greek-life college students, this population may be particularly at
risk for experiencing negative outcomes during this time. Thus, the current study
utilized a Deviance Regulation Theory (DRT)-based approach to increase the use of
protective behavioral strategies (PBS) among Greek-life college students during
spring break. Greek-life college students going on spring break (n = 89)
completed a screening before being randomly assigned to a pre-spring break
condition (i.e., either a positively or negatively framed message about peers who
do or do not use PBS during spring break). Participants then completed a post
spring break assessment of alcohol and PBS use over spring break (n = 70). There
were no observed DRT effects on manner of drinking or stopping/limiting PBS use
during spring break. However, there were effects on Harm Reduction PBS (HR PBS).
In the positive frame, HR PBS use was positively associated with PBS norm
discrepancy (the difference between spring break specific PBS norms and typical
PBS norms). While these associations did not result in lower alcohol consumption,
HR PBS was inversely associated with risk-related alcohol problems, but not other
types of alcohol problems. A brief DRT-based approach may increase specific PBS
types during spring break and may reduce risk-related alcohol-related problems
among Greek-life students during spring break. (PsycINFO Database Record
PMID- 29952615
TI - A review of the effects of nicotine on social functioning.
AB - Many smokers are aware that smoking is a dangerous health behavior and eventually
try to quit smoking. Unfortunately, most quit attempts end in failure.
Traditionally, the addictive nature of smoking has been attributed to the
pharmacologic effects of nicotine. In an effort to offer a more comprehensive,
biobehavioral analysis of smoking behavior and motivation, some researchers have
begun to consider the role of social factors in smoking. In line with recent
recommendations to integrate social and pharmacological analyses of smoking, we
reviewed the experimental literature examining the effects of nicotine and
nicotine withdrawal on social functioning. The review identified 13 studies that
experimentally manipulated nicotine and assessed social functioning, 12 of which
found support for nicotine's enhancement of social functioning. Although few
experiments have investigated social functioning, they nevertheless offer
compelling evidence that nicotine enhances social functioning in smokers and
suggest that nicotine deprivation may hamper social functioning in those
dependent on nicotine. Future directions for investigating social outcomes and
context in those who use nicotine products are discussed with a focus on
leveraging advances in social and developmental psychology, animal research,
sociology, and neuroimaging to more comprehensively understand smoking behavior.
(PsycINFO Database Record (c) 2018 APA, all rights reserved).
PMID- 29952618
TI - Effects of lorcaserin and buspirone, administered alone and as a mixture, on
cocaine self-administration in male and female rhesus monkeys.
AB - Cocaine use disorder is a serious public health issue for which there is no
effective pharmacotherapy. One strategy to speed development of medications for
cocaine use disorder is to repurpose drugs already approved for use in humans
based on their ability to interact with targets known to be important for
addiction. Two such drugs, lorcaserin (Belviq; a drug with serotonin [5-HT]2C
receptor agonist properties) and buspirone (Buspar; a drug with 5-HT1A receptor
partial agonist and dopamine D3/D4 receptor antagonist properties) can produce
modest decreases in cocaine self-administration in rhesus monkeys. The current
study evaluated the effectiveness of mixtures of lorcaserin and buspirone (at
fixed dose ratios of 3:1, 1:1, and 1:3 relative to each drug's ID50) to reduce
responding for 0.032 mg/kg/inf cocaine under a progressive ratio schedule of
reinforcement in 2 male and 2 female rhesus monkeys. Dose addition analyses were
used to determine if the effects of the drug mixtures differed from those
predicted for an additive interaction between lorcaserin and buspirone. Dose
dependent reductions of cocaine self-administration were observed when lorcaserin
and buspirone were administered alone, as well as when they were administered as
3:1, 1:1, and 1:3 fixed ratio mixtures of lorcaserin + buspirone. The effects of
the 1:1 mixture of lorcaserin + buspirone on cocaine self-administration were
supraadditive, whereas the effects of 3:1 and 1:3 mixtures were additive.
Together, these results indicate that a combination therapy containing a mixture
of lorcaserin and buspirone might be more effective than either drug alone at
treating cocaine use disorder. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29952619
TI - Self-regulation as a mediator of the effects of a brief behavioral economic
intervention on alcohol-related outcomes: A preliminary analysis.
AB - Behavioral economic theory suggests that increased engagement in constructive,
substance-free activities that are in the service of long-term goals (e.g.,
college graduation, career development, health) can decrease alcohol use and
related problems. However, engaging in activities such as these in the high-risk
college environment requires the ability to self-regulate by avoiding rewarding
but risky behaviors (e.g., drinking) while also effectively organizing behavior
in the pursuit of delayed academic and career-related rewards. The current
secondary data analyses evaluated self-regulation as a potential mechanism of
behavior change in an alcohol intervention trial that compared a standard alcohol
focused brief motivational intervention (BMI) plus a behavioral economic
substance-free activity session (SFAS) with an alcohol BMI plus relaxation
training (reaction time [RT]) session (Murphy et al., 2012). Participants were 82
first-year undergraduate students (50% women; Mage = 18.5, SD = .71) who reported
2 or more past-month heavy drinking episodes. After completing a baseline
assessment and an individual alcohol-focused BMI, participants were randomized to
either the SFAS or the RT session. The BMI + SFAS condition reported greater mean
self-regulation at 1 month compared with BMI + RT. Furthermore, self-regulation
at 1 month significantly mediated the relation between condition and alcohol
related outcomes at 6-month follow-up. Although preliminary, these results
suggest that brief behavioral economic intervention elements that an attempt to
increase future goal pursuit and substance-free activities can enhance the short
term efficacy of standard alcohol BMIs and that this effect may be due in part to
increases in self-regulation. (PsycINFO Database Record
PMID- 29952620
TI - Automatic control: How experts act without thinking.
AB - Experts act without thinking because their skill is hierarchical. A single
conscious thought automatically produces a series of lower-level actions without
top-down monitoring. This article presents a theory that explains how automatic
control is possible in skilled typing, where thinking of a word automatically
produces a rapid series of keystrokes. The theory assumes that keystrokes are
selected by a context retrieval process that matches the current context to
stored contexts and retrieves the key associated with the best match. The current
context is generated by the typist's own actions. It represents the goal ("type
DOG") and the motor commands for the keys struck so far. Top-down control is
necessary to start typing. It sets the goal in the current context, which
initiates the retrieval and updating processes, which continue without top-down
control until the word is finished. The theory explains phenomena of hierarchical
control in skilled typing, including differential loads on higher and lower
levels of processing, the importance of words, and poor explicit knowledge of key
locations and finger-to-key mappings. The theory is evaluated by fitting it to
error corpora from 24 skilled typists and predicting error probabilities,
magnitudes, and patterns. Some of the fits are quite good. The theory has
implications beyond typing. It argues that control can be automatic and shows how
it is possible. The theory extends to other sequential skills, like texting or
playing music. It provides new insights into mechanisms of serial order in
typing, speaking, and serial recall. (PsycINFO Database Record
PMID- 29952621
TI - Chunking as a rational strategy for lossy data compression in visual working
memory.
AB - The nature of capacity limits for visual working memory has been the subject of
an intense debate that has relied on models that assume items are encoded
independently. Here we propose that instead, similar features are jointly encoded
through a "chunking" process to optimize performance on visual working memory
tasks. We show that such chunking can: (a) facilitate performance improvements
for abstract capacity-limited systems, (b) be optimized through reinforcement,
(c) be implemented by center-surround dynamics, and (d) increase effective
storage capacity at the expense of recall precision. Human performance on a
variant of a canonical working memory task demonstrated performance advantages,
precision detriments, interitem dependencies, and trial-to-trial behavioral
adjustments diagnostic of performance optimization through center-surround
chunking. Models incorporating center-surround chunking provided a better
quantitative description of human performance in our study as well as in a meta
analytic dataset, and apparent differences in working memory capacity across
individuals were attributable to individual differences in the implementation of
chunking. Our results reveal a normative rationale for center-surround
connectivity in working memory circuitry, call for reevaluation of memory
performance differences that have previously been attributed to differences in
capacity, and support a more nuanced view of visual working memory capacity
limitations: strategic tradeoff between storage capacity and memory precision
through chunking contribute to flexible capacity limitations that include both
discrete and continuous aspects. (PsycINFO Database Record
PMID- 29952622
TI - Multialternative decision by sampling: A model of decision making constrained by
process data.
AB - Sequential sampling of evidence, or evidence accumulation, has been implemented
in a variety of models to explain a range of multialternative choice phenomena.
But the existing models do not agree on what, exactly, the evidence is that is
accumulated. They also do not agree on how this evidence is accumulated. In this
article, we use findings from process-tracing studies to constrain the evidence
accumulation process. With these constraints, we extend the decision by sampling
model and propose the multialternative decision by sampling (MDbS) model. In
MDbS, the evidence accumulated is outcomes of pairwise ordinal comparisons
between attribute values. MDbS provides a quantitative account of the attraction,
compromise, and similarity effects equal to that of other models, and captures a
wider range of empirical phenomena than other models. (PsycINFO Database Record
PMID- 29952623
TI - Hilbert space multidimensional theory.
AB - A general theory of measurement context effects, called Hilbert space
multidimensional (HSM) theory, is presented. A measurement context refers to a
subset of psychological variables that an individual evaluates on a particular
occasion. Different contexts are formed by evaluating different but possibly
overlapping subsets of variables. Context effects occur when the judgments across
contexts cannot be derived from a single joint probability distribution over the
complete set of values of the observed variables. HSM theory provides a way to
model these context effects by using quantum probability theory, which represents
all the variables within a low dimensional vector space. HSM models produce
parameter estimates that provide a simple and informative interpretation of the
complex collection of judgments across contexts. Comparisons of HSM model fits
with Bayesian network model fits are reported for a new large experiment,
demonstrating the viability of this new model. We conclude that the theory is
broadly applicable to measurement context effects found in the social and
behavioral sciences. (PsycINFO Database Record
PMID- 29952624
TI - Refining the law of practice.
AB - The "law of practice"-a simple nonlinear function describing the relationship
between mean response time (RT) and practice-has provided a practically and
theoretically useful way of quantifying the speed-up that characterizes skill
acquisition. Early work favored a power law, but this was shown to be an artifact
of biases caused by averaging over participants who are individually better
described by an exponential law. However, both power and exponential functions
make the strong assumption that the speedup always proceeds at a steadily
decreasing rate, even though there are sometimes clear exceptions. We propose a
new law that can both accommodate an initial delay resulting in a slower-faster
slower rate of learning, with either power or exponential forms as limiting
cases, and which can account for not only mean RT but also the effect of practice
on the entire distribution of RT. We evaluate this proposal with data from a
broad array of tasks using hierarchical Bayesian modeling, which pools data
across participants while minimizing averaging artifacts, and using inference
procedures that take into account differences in flexibility among laws. In a
clear majority of paradigms our results supported a delayed exponential law.
(PsycINFO Database Record
PMID- 29952626
TI - Need depriving effects of financial insecurity: Implications for well-being and
financial behaviors.
AB - Evidence suggests that experiencing financial insecurity lowers well-being and
increases problematic financial behaviors. The present article employs a self
determination theory (SDT; R. M. Ryan & Deci, 2000a) perspective to understand
the mechanisms by which experiencing financial insecurity contributes to these
detrimental outcomes. Informed by SDT, we expected that the basic psychological
needs for autonomy, competence, and relatedness would drive these effects.
Studies were concerned with individuals' general experiences of financial
insecurity (using community samples; Studies 1 and 2), and employed manipulations
involving self-reflection (Study 3) and hypothetical scenarios (Study 4).
Findings demonstrated that financially insecure conditions undermined basic
psychological needs and lowered well-being (measured in terms of self-esteem,
depression, and anxiety). In addition, lower satisfaction of basic psychological
needs linked financial insecurity to a greater likelihood of engaging in
financial cheating (Studies 2 and 3) and risky financial decisions (Study 4).
Importantly, this pattern of effects remained in evidence across
socioeconomically diverse samples and income levels. We discuss implications for
future interventions to improve the wellness of individuals in financially
insecure circumstances. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 29952625
TI - Don't blame the model: Reconsidering the network approach to psychopathology.
AB - The network approach to psychopathology is becoming increasingly popular. The
motivation for this approach is to provide a replacement for the problematic
common cause perspective and the associated latent variable model, where symptoms
are taken to be mere effects of a common cause (the disorder itself). The idea is
that the latent variable model is plausible for medical diseases, but unrealistic
for mental disorders, which should rather be conceptualized as networks of
directly interacting symptoms. We argue that this rationale for the network
approach is misguided. Latent variable (or common cause) models are not
inherently problematic, and there is not even a clear boundary where network
models end and latent variable (or common cause) models begin. We also argue that
focusing on this contrast has led to an unrealistic view of testing and finding
support for the network approach, as well as an oversimplified picture of the
relationship between medical diseases and mental disorders. As an alternative, we
point out more essential contrasts, such as the contrast between dynamic and
static modeling approaches that can provide a better framework for
conceptualizing mental disorders. Finally, we discuss several topics and open
problems that need to be addressed in order to make the network approach more
concrete and to move the field of psychological network research forward.
(PsycINFO Database Record
PMID- 29952627
TI - Saccade trajectories reveal dynamic interactions of semantic and spatial
information during the processing of implicitly spatial words.
AB - Implicit up/down words, such as bird and foot, systematically influence
performance on visual tasks involving immediately following targets in compatible
versus incompatible locations. Recent studies have observed that the semantic
relation between prime words and target pictures can strongly influence the size
and even the direction of the effect: Semantically related targets are processed
faster in congruent versus incongruent locations (location-specific priming),
whereas unrelated targets are processed slower in congruent locations. Here, we
used eye-tracking to investigate the moment-to-moment processes underlying this
pattern. Our reaction time (RT) results for related targets replicated the
location-specific priming effect and showed a trend toward interference for
unrelated targets. We then used growth curve analysis to test how up/down words
and their match versus mismatch with immediately following targets in terms of
semantics and vertical location influence concurrent saccadic eye movements.
There was a strong main effect of spatial association on linear growth, with up
words biasing changes in y-coordinates over time upward relative to down words
(and vice versa). Similar to the case with the RT data, this effect was strongest
for semantically related targets and reversed for unrelated targets. It is
intriguing that all conditions showed a bias in the congruent direction in the
initial stage of the saccade. Then, at around halfway into the saccade the effect
kept increasing in the semantically related condition and reversed in the
unrelated condition. These results suggest that online processing of up/down
words triggers direction-specific oculomotor processes that are dynamically
modulated by the semantic relation between prime words and targets. (PsycINFO
Database Record (c) 2018 APA, all rights reserved).
PMID- 29952628
TI - All categories are equal, but some categories are more equal than others: The
psychometric structure of object and face cognition.
AB - Recent research on individual differences in object cognition (OC) focused on
determining how objects group together, and what type of processing lies behind
the clusters-a single domain-general or multiple domain-specific processes. The
expertise hypothesis suggests that all object categories are processed by the
same mechanism that is responsible for differentiating visually similar objects.
This ability is expected to be more specifically expressed in processing objects
for which people have higher expertise. The domain-specificity hypothesis
postulates that different object categories, for example, living versus nonliving
objects, are processed employing different mechanisms. In the present study we
aimed to study (a) how multiple objects group together in terms of individual
differences; (b) the expertise hypothesis based on up-to-date statistical methods
of modeling individual differences; (c) whether task difficulty influences the
structure of individual differences in OC. We applied a memory task to N = 186
participants, by using multiple, theoretically chosen object categories divided
into five groups-living/mobile (fish, butterflies), living/immobile (flowers,
leaves), nonliving/mobile (cars, motorbikes), nonliving/immobile (houses, chairs)
and faces-and report three main findings. (a) In terms of individual differences,
the factor space of OC can be accounted by three factors-general OC factor along
with a specific Vehicle and Face factor; (b) there is no clear evidence for the
expertise hypothesis; and (c) task difficulty does not influence the OC
structure. We conclude that domain-specific mechanisms in object processing
cannot be dismissed. (PsycINFO Database Record
PMID- 29952629
TI - Strategy selection versus flexibility: Using eye-trackers to investigate strategy
use during mental rotation.
AB - Spatial researchers have been arguing over the optimum cognitive strategy for
spatial problem-solving for several decades. The current article aims to shift
this debate from strategy dichotomies to strategy flexibility-a cognitive
process, which although alluded to in spatial research, presents practical
methodological challenges to empirical testing. In the current study,
participants' eye movements were tracked during a mental rotation task (MRT)
using the Tobii *60 eye-tracker. Results of a latent profile analysis, combining
different eye movement parameters, indicated two distinct eye-patterns-fixating
and switching patterns. The switching eye-pattern was associated with high mental
rotation performance. There were no sex differences in eye-patterns. To
investigate strategy flexibility, we used a novel application of the changepoint
detection algorithm on eye movement data. Strategy flexibility significantly
predicted mental rotation performance. Male participants demonstrated higher
strategy flexibility than did female participants. Our findings highlight the
importance of strategy flexibility in spatial thinking and have implications for
designing spatial training techniques. The novel approaches to analyzing eye
movement data in the current paper can be extended to research beyond the spatial
domain. (PsycINFO Database Record
PMID- 29952630
TI - Lexical knowledge boosts statistically-driven speech segmentation.
AB - The hypothesis that known words can serve as anchors for discovering new words in
connected speech has computational and empirical support. However, evidence for
how the bootstrapping effect of known words interacts with other mechanisms of
lexical acquisition, such as statistical learning, is incomplete. In 3
experiments, we investigated the consequences of introducing a known word in an
artificial language with no segmentation cues other than cross-syllable
transitional probabilities. We started with an artificial language containing 4
trisyllabic novel words and observed standard above-chance performance in a
subsequent recognition memory task. We then replaced 1 of the 4 novel words with
a real word (tomorrow) and noted improved segmentation of the other 3 novel
words. This improvement was maintained when the real word was a different length
to the novel words (philosophy), ruling out an explanation based on metrical
expectation. The improvement was also maintained when the word was added to the 4
original novel words rather than replacing 1 of them. Together, these results
show that known words in an otherwise meaningless stream serve as anchors for
discovering new words. In interpreting the results, we contrast a mechanism where
the lexical boost is merely the consequence of attending to the edges of known
words, with a mechanism where known words enhance sensitivity to transitional
probabilities more generally. (PsycINFO Database Record
PMID- 29952631
TI - Long-term follow-up of cryopreserved amniotic membrane transplant during
strabismus reoperations: Up 85 months' follow-up.
AB - PURPOSE: To evaluate the long-term effect of cryopreserved human amniotic
membrane transplant during strabismus reoperations. METHODS: A total of 15
patients with persistent strabismus were included in a prospective study to
evaluate the effect of wrapping the extra-ocular muscles with cryopreserved
amniotic membrane during strabismus reoperations. The study end-point was the
last follow-up visit. A successful outcome was defined as 0-10? of horizontal
tropia and 0-4? of vertical tropia, with no limitation of ductions exceeding -1.
A cosmetically acceptable outcome was defined as a tropia of 0-15?. RESULTS:
Maximum follow-up was 85 months (mean: 25.4 +/- 25.5 months). At the last follow
up visit, a successful outcome was achieved in 46.7%, a cosmetically acceptable
outcome was achieved in 66.7%, and the mean ocular deviation angles improved from
38.60 +/- 14.63?, preoperatively, to 10.6 +/- 11.08?. Motility limitation on the
final follow-up visit exceeded -1 in only 4/180 muscles (2.2%). CONCLUSION: The
effect of cryopreserved amniotic membrane transplantation on the success of
strabismus reoperations was moderate in terms of ocular alignment. Its effect was
more pronounced in terms of ocular motility. The latter better reflects the level
of adhesions. No long-term complications were documented, denoting safety of
cryopreserved amniotic membrane usage during strabismus reoperations.
PMID- 29952632
TI - External Nasal Valve Repair in Children: Alar Batten Graft Reinforced by External
Temporary Suspensory Suture.
AB - BACKGROUND: The nasal valve area is the narrowest point in the nasal airway.
External nasal valve (ENV) collapse during inspiration occurs if external valve
area is too narrow or its lateral component is too floppy. PATIENTS AND METHOD:
Twelve patients (7 males, 5 females) aged 8 to 12 years complaining of nasal
obstruction due to ENV dysfunction underwent surgical intervention using alar
batten graft assisted by temporary external suspensory suture. RESULTS: All
patients showed subjective and objective improvement of the nasal airway. The
mean Nasal Obstructive Symptom Evaluation (NOSE) was 14 +/- 1.71 before surgery
and 7.83 +/- 1.47 1 year after surgery (significant improvement, p <= .0001). The
mean Peak Inspiratory Flow Rate was 29.92 +/- 4.46 before surgery and 42.58 +/-
4.93 1 year after surgery (significant improvement, P <= .0001). CONCLUSION:
External nasal valve collapse in children can be managed surgically by using alar
batten graft. Temporary suspension suture can be helpful for supporting of the
graft until complete healing occurs.
PMID- 29952633
TI - Pathophysiology, diagnosis and management of MINOCA: an update.
AB - Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a
syndrome with different causes, characterised by clinical evidence of myocardial
infarction with normal or near-normal coronary arteries on angiography. Its
prevalence ranges between 5% and 25% of all myocardial infarction. The prognosis
is extremely variable, depending on the cause of MINOCA. The key principle in the
management of this syndrome is to clarify the underlying individual mechanisms to
achieve patient-specific treatments. Clinical history, electrocardiogram, cardiac
enzymes, echocardiography, coronary angiography and left ventricular angiography
represent the first level diagnostic investigations to identify the causes of
MINOCA. Regional wall motion abnormalities at left ventricular angiography
limited to a single epicardial coronary artery territory identify an 'epicardial
pattern'whereas regional wall motion abnormalities extended beyond a single
epicardial coronary artery territory identify a 'microvascular pattern'. The most
common causes of MINOCA are represented by coronary plaque disease, coronary
dissection, coronary artery spasm, coronary microvascular spasm, Takotsubo
cardiomyopathy, myocarditis, coronary thromboembolism, other forms of type 2
myocardial infarction and MINOCA of uncertain aetiology. This review aims at
summarising the diagnosis and management of MINOCA, according to the underlying
physiopathology.
PMID- 29952634
TI - Training Periodization Over an Elite Rugby Sevens Season: From Theory to
Practice.
AB - PURPOSE: To describe the training periodization in Rugby-7s players competing in
the Sevens World Series during a non-Olympic season. METHODS: Workload data were
collected over a 33-week period in twelve male players participating in a full
competitive season. Workload was quantified using session RPE and GPS-derived
data during training and competition. Self-reported wellbeing was assessed using
a questionnaire. Each variable was analysed weekly and through 5 mesocycles (Pre
season, In-season 1-4), each of which ended with competition blocks. RESULTS: The
perceived load decreased throughout the season for the full squad (-68 +/- 26%
between pre-season and final competitive block, large effect) and when
unavailable players were removed from the analysis (-38 +/- 42%, moderate).
Weekly perceived load was highly variable with a typical periodization in 4
phases during each mesocycle (regeneration, training overload, taper and
competition). During the pre-season, the workload was higher during the overload
training phase than during the competitive period (range: +23-59%, large to very
large, for the distance covered above individual maximal aerobic speed and the
number of accelerations). This observation no longer persisted during the in
season. The wellbeing score decreased almost certainly from In-3 (moderate).
CONCLUSIONS: These results highlighted the apparent difficulty in maintaining
high-load training periods throughout the season in players engaged on the Sevens
World Series despite ~4-7 training weeks separating each competitive block. This
observation was likely explained by the difficulties inherent to the Sevens World
Series (risk of contact injury, calendar and multiple long-haul travel) and
potentially by limited squad rotation policies.
PMID- 29952636
TI - Position Available - Editor, Anesthesia Progress.
PMID- 29952635
TI - Corrigendum.
PMID- 29952637
TI - A Review of Current Literature of Interest to the Office-Based Anesthesiologist.
PMID- 29952638
TI - Anesthetic Management of the Hypertensive Patient: Part I.
AB - Hypertension is an important health challenge that affects millions of people
across the world and is a major risk factor for cardiovascular disease. It is
critical that anesthesia providers have a working knowledge of the systemic
implications of hypertension. This review article will discuss the medical
definitions of hypertension, the physiology of maintaining blood pressure,
outpatient treatment of hypertension, anesthetic implications, and the common
medications used by anesthesia providers in the treatment of hypertension. Part I
will provide an overview of hypertension and blood pressure regulation. In
addition, drugs affecting predominantly renal control of hypertension, such as
diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor
blockers, and renin-inhibiting agents, will be discussed. In part II, the
remaining major antihypertensive medications will be reviewed as well as
anesthetic implications of managing patients with hypertension.
PMID- 29952640
TI - Come to IFDAS in Nara, Japan.
PMID- 29952639
TI - Utility of Vibratory Stimulation for Reducing Intraoral Injection Pain.
AB - Intraoral local anesthesia injection is often perceived as a painful and anxiety
causing dental procedure. Vibration stimulus is one of the nonpharmacologic
methods used to reduce unwanted sensations of local anesthesia injection. This
clinical study evaluated the effectiveness of a recently introduced vibratory
stimulation device in intraoral local anesthesia administration. Thirty-two
subjects underwent 2 maxillary local anesthesia injections in 2 different
sessions: 1 with conventional techniques and 1 with the aid of a vibratory
stimulation device (DentalVibe). The pain levels were evaluated with a visual
analog scale and the Wong-Baker FACES Pain Rating Scale. The subjects were asked
to choose the preferred method for future injections. The data were evaluated
statistically. There were no significant differences between the 2 injection
methods with regard to either pain evaluation method. The preference of the
subjects regarding future injection technique was evenly distributed between the
groups. The vibratory stimulation device used in this study did not provide any
reduction in pain level associated with maxillary infiltration local anesthesia
administration.
PMID- 29952641
TI - The Effect of Adding Midazolam to Propofol Intravenous Sedation to Suppress Gag
Reflex During Dental Treatment.
AB - We retrospectively investigated the efficacy and safety of propofol
administration alone and in combination with midazolam for gag reflex suppression
during dental treatment under intravenous sedation. We included 56 patients with
an overactive gag reflex who were to undergo dental treatment under intravenous
sedation. They were divided into propofol (P group, n = 22) and midazolam with
propofol (MP group, n = 34) groups. The P group received propofol alone, while
the MP group received midazolam (0.04 mg/kg) prior to target-controlled infusion
(TCI) of propofol (titrated for adequate sedation). The patients' anesthetic
records were evaluated for vital sign changes, adverse cardiovascular or
respiratory event frequency, the number of forced treatment interruptions, and
the TCI-predicted cerebral propofol concentration at gag reflex suppression
(posterior tongue stimulation with a dental mirror). No significant differences
were observed between the 2 groups preoperatively. There were no cases of forced
interruptions or significant respiratory compromise in either group.
Cardiovascular adverse event frequency was lower in the MP group than in the P
group (all p < .05). Our results suggest that propofol, when combined with
midazolam, minimized cardiovascular effects compared with propofol alone when
used to suppress the gag reflex in patients during dental treatment under
intravenous sedation.
PMID- 29952642
TI - Sugammadex: Efficacy and Practicality in the Dental Office.
AB - Sugammadex is a novel drug capable of reversing paralysis induced by the common
steroidal nondepolarizing neuromuscular blocking drugs, rocuronium and
vecuronium. Reversal is complete at any depth of blockade dependent on the dose
of sugammadex administered. This allows rocuronium to be used as a rescue agent
in scenarios where succinylcholine is contraindicated. Sugammadex is considered a
safe drug with minimal side effects compared with traditional reversal with
neostigmine and glycopyrrolate. This article features a case report where
succinylcholine was undesirable and rapid reversal of paralysis with sugammadex
was used during general anesthesia for dentistry.
PMID- 29952643
TI - Sedation With a Combination of Dexmedetomidine and Midazolam for Pediatric Dental
Surgery.
AB - Intravenous sedation (IVS) is commonly used to complete dental treatment for
uncooperative pediatric patients. Propofol (PRO) is widely used for IVS because
of its short context sensitive half-time and amnestic effect. However,
administering PRO to patients who have a history of egg anaphylaxis is still
somewhat controversial. The evidence that supports the potential risks for
allergic reactions following PRO use in patients with egg allergies is limited
with some anesthesiologists recommending against its use in these patients.
Alternative drug regimens for procedural sedation in this population are
therefore desirable. Dexmedetomidine (DEX), a selective alpha-2 agonist, has
antianxiety and sedative properties and has been widely used not only for
procedural sedation with mild inhibitory effects on respiration but also during
minor surgeries for its analgesic effect. In this paper, we describe the
successful administration of a combination of DEX and low-dose midazolam (MDZ)
for sedation in an uncooperative pediatric patient. Both DEX and MDZ have been
reported as safe and useful sedatives for dental treatment, and their combination
may provide a helpful option for IVS of pediatric patients for whom PRO is not
preferred.
PMID- 29952644
TI - Effects of Lidocaine and Articaine on Neuronal Survival and Recovery.
AB - The local anesthetics lidocaine and articaine are among the most widely used
drugs in the dentist's arsenal, relieving pain by blocking voltage-dependent Na+
channels and thus preventing transmission of the pain signal. Given reports of
infrequent but prolonged paresthesias with 4% articaine, we compared its
neurotoxicity and functional impairment by screening cultured neural SH-SY5Y
cells with formulations used in patients (2% lidocaine + 1:100,000 epinephrine or
4% articaine + 1:100,000 epinephrine) and with pure formulations of the drugs.
Voltage-dependent sodium channels Na(v)1.2 and Na(v)1.7 were expressed in SH-SY5Y
cells. To test the effects on viability, cells were exposed to drugs for 5
minutes, and after washing, cells were treated with the ratiometric Live/Dead
assay. Articaine had no effect on the survival of SH-SY5Y cells, while lidocaine
produced a significant reduction only when used as pure powder. To determine
reversibility of blockage, wells were exposed to drugs for 5 minutes and returned
for medium for 30 minutes, and the calcium elevation induced by depolarizing
cells with a high-potassium solution was measured using the calcium indicator
Fura-2. High potassium raised calcium in control SH-SY5Y cells and those treated
with articaine, but lidocaine treatment significantly reduced the response. In
conclusion, articaine does not damage neural cells more than lidocaine in this in
vitro model. While this does not question the safety of lidocaine used
clinically, it does suggest that articaine is no more neurotoxic, at least in the
in vitro setting.
PMID- 29952645
TI - True Allergy to Amide Local Anesthetics: A Review and Case Presentation.
AB - Adverse reactions to local anesthetics are usually a reaction to epinephrine,
vasovagal syncope, or overdose toxicity. Allergic reactions to local anesthetics
are often attributed to additives such as metabisulfite or methylparaben. True
allergic reactions to amide local anesthetics are extremely rare but have been
documented. Patients with true allergy to amide local anesthetics present a
challenge to the dental practitioner in providing adequate care with appropriate
intraoperative pain management. Often, these patients may be treated under
general anesthesia. We report a case of a 43-year-old female patient that
presented to NYU Lutheran Medical Center Dental Clinic with a documented history
of allergy to amide local anesthetics. This case report reviews the use of 1%
diphenhydramine with 1:100,000 epinephrine as an alternative local anesthetic and
reviews the relevant literature.
PMID- 29952646
TI - Tapia's Syndrome.
AB - More than 100,000 general anesthetic procedures are conducted in United Kingdom
every year for dental interventions, according to large survey of the National
Health Services. 1 The risk of mortality has reduced considerably in the past few
decades because of the use of safe and effective techniques. However, adverse
effects still exist and are dependent on patient, environmental, and operator
factors. We present an uncommon complication of intubation that merits due
awareness.
PMID- 29952647
TI - A Case of General Anesthesia for a Young Infant in Whom Intubation Was Suspected
to Be Difficult Because of a Thyrolingual Cyst.
AB - This is a case report of an infant who underwent thyrolingual cystectomy under
general anesthesia. Two tracheal tubes were used: 1 for nasopharyngeal airway and
the other for fiberoptic intubation. With this method, nasal intubation was
successfully performed without hypoxia and hypercapnia even in a 3-month-old
infant. We concluded this is a useful intubation method for infants who are
predicted to be a difficult intubation.
PMID- 29952648
TI - Pilot Study Comparing Nasal vs Oral Intubation for Dental Surgery by Physicians,
Nurse Anesthetists, and Trainees.
AB - The purpose of this article was to determine if pediatric dental treatment under
general anesthesia utilizing orotracheal intubation takes longer than using
nasotracheal intubation techniques. Twenty-six American Society of
Anesthesiologists Physical Status Classification I and II pediatric dental
patients, ages 2-8 years treated under general anesthesia, were assigned to 1 of
2 groups: (a) nasotracheal intubation (control, n = 13), (b) orotracheal
intubation (experimental, n = 13). Times for intubation, radiographic imaging,
and dental procedures, as well as total case time were quantified. Data were
collected on airway difficulty, numbers of providers needed for intubation,
intubation attempts, and intubation trauma. There was a significant difference in
mean intubation time (oral = 2.1 minutes versus nasal = 6.3 minutes; p < .01).
There was no difference in mean radiograph time (oral = 4.2 minutes versus nasal
= 3.4 minutes; p = .144), and overall radiograph image quality was not affected.
There was no difference in dental procedure time ( p = .603) or total case time (
p = .695). Additional providers were needed for intubation and more attempts were
required for nasotracheal intubation versus orotracheal intubation (6 additional
providers/22 attempts vs 0 additional providers/15 attempts, p < .01 and p < .05,
respectively). Nine of 13 nasotracheal intubations were rated as traumatic (69%)
versus 0 of 13 for orotracheal intubations (0%) ( p < .01). In 7/9 orotracheal
intubation cases (78%), the tube was not moved during treatment ( p < .01).
Orotracheal intubation does not increase case time, does not interfere with
radiographic imaging, and is less traumatic for the patient when performed by
physician anesthesiologists, emergency and pediatric medicine physician
residents, certified registered nurse anesthetists, and student nurse
anesthetists, all with variable nasotracheal intubation experience.
PMID- 29952649
TI - Thermophysical Properties of Thermosoftening Nasotracheal Tubes.
AB - Thermosoftening treatment of polyvinyl chloride (PVC) nasotracheal tubes (NTTs)
can reduce the incidence and amount of epistaxis during nasotracheal intubation.
The optimal thermal setting for thermosoftening treatment of NTTs without burn
injury was investigated. Two composite types of PVC NTTs were used. Following
withdrawal of the PVC NTTs from a bottle of water at 45 or 60 degrees C, the
changes in the surface temperature of the NTTs were measured by infrared
thermography. Hardness of the NTTs at 25, 30, 35, and 40 degrees C was measured.
The incidence of epistaxis during nasotracheal intubation using thermosoftened
NTTs was evaluated retrospectively. The surface temperature of both PVC NTTs
dipped in 45 and 60 degrees C water decreased to below body temperature 30
seconds after withdrawing them from the bottles. Although thermosoftening
treatment proportionally decreased the hardness of both types of NTTs, the
degrees differed according to their composition. When avoiding impingement of the
NTT on the posterior wall of the nasopharynx, the incidence of mild and moderate
epistaxis was 2.3%. Flexibility of PVC NTTs could be obtained by thermosoftening
treatment at 60 degrees C without burn injury. Thermosoftening treatment of PVC
NTTs may be useful to avoid epistaxis during nasotracheal intubation.
PMID- 29952651
TI - Commentary.
PMID- 29952650
TI - Retained Foreign Body in the Nasal Cavity After Oral Maxillofacial Surgery.
AB - Retained foreign bodies sometimes occur in various surgical procedures and can
lead to severe complications. Foreign bodies in the oral and maxillofacial region
are not rare because of the use of many small items and the natural communication
with the outside environment in some areas. We experienced a case of foreign body
in the nasal cavity, which was discovered 1 year later at a second operation for
hardware removal after maxillofacial surgery. A small, soft material is usually
placed between the nasal endotracheal tube and nostril to avoid nasal pressure
ulcer at the ala of nose after prolonged anesthesia after our group's
experiencing some cases of this complication. The foreign body was found in the
pharynx during induction of a second anesthesia. Attention should be directed to
not leaving any materials in the patient after surgery. In addition to the normal
counts of sponges, needles, etc, other small nonsurgical materials used should be
recorded by medical staff to help ensure nothing is retained in the patient.
PMID- 29952652
TI - Alternating Current Iontophoresis for Control of Postoperative Pain.
AB - Control of early postoperative pain entails the use of various medications
including acetaminophen, nonsteroidal anti-inflammatory drugs, selective
cyclooxygenase-2 inhibitors, tramadol, and opioids. However, these medications
should be carefully administered in patients with aspirin-exacerbated respiratory
disease because some medications may trigger adverse reactions after
maxillofacial surgeries. The goal of postoperative pain control in patients with
aspirin-exacerbated respiratory disease is to eliminate pain without
complications. Local anesthesia is an efficient tool for the control of
postoperative pain after maxillofacial surgeries. We utilized a transdermal drug
delivery system, iontophoresis by alternating current, in order to develop an
alternative technique for administering local anesthetic to control postoperative
pain in 2 patients with aspirin-exacerbated respiratory disease. A visual
analogue scale was used to objectively measure the severity of pain. A 55-year
old woman who underwent mandibular wisdom tooth extraction and an 18-year-old
woman who underwent sagittal split ramus osteotomy of the mandible both
complained of pain multiple times. After application of iontophoresis, the visual
analogue scale score was reduced to zero and postoperative pain could be
controlled. There were no adverse events such as bronchospasm or skin irritation
after the application of iontophoresis by alternating current.
PMID- 29952653
TI - Analysis of miRNA expression profiling identifies miR-214-3p as a novel biomarker
in sinonasal inverted papilloma.
AB - AIM: To analyze the expression profile, diagnostic and clinicopathological
significances of miRNAs in sinonasal inverted papilloma (SNIP). MATERIALS &
METHODS: The expression profile of miRNAs was analyzed using a miRNA microarray
approach. The potential functions and clinical significances of specific miRNAs
were further analyzed by bioinformatics and statistical methods. RESULTS: The
microarray assay identified 37 significantly upregulated and 21 downregulated
miRNAs in SNIP. Of nine miRNAs randomly selected, the expression levels of seven
miRNAs were confirmed by quantitative real-time PCR. The potential target genes
of several candidate miRNAs were enriched in some biological processes and
cellular signaling pathways related to tumorigenesis. Receiever operating
characteristic curve analysis for miR-214-3p indicated an area under the curve of
0.932. Notably, its expression level was significantly decreased in SNIP tissues
and associated with SNIP staging and recurrence. CONCLUSION: MiR-214-3p can
possibly serve as a valuable biomarker and a therapeutic target for SNIP.
PMID- 29952654
TI - Concentrations of Intact Insulin Concurs With FDA and EMA Standards When Measured
by HPLC in Different Parts of the Distribution Cold Chain.
AB - BACKGROUND: The article by Carter and Heinemann raised serious concerns about the
concentrations of insulin in vials being sold in US pharmacies. To study the
claims made in the manuscript, we reviewed Novo Nordisk data on insulin
concentration. METHODS: Insulin concentrations within vials from three different
sources along the distribution chain were evaluated utilizing currently accepted
US Pharmacopeia methodology: (1) insulin content and stability based on
production batches covering 7 years of insulin production, (2) insulin content in
samples returned to Novo Nordisk over the last three years in the United States,
and (3) data from eight years of independent EMA testing. RESULTS: The data
demonstrated that without exception (1) insulin quality based on stability data
was maintained, even in scenarios that stressed the normal recommendations for
temperature storage conditions, (2) insulin content from the last three years of
samples returned to Novo Nordisk from patients in the United States (233 vials)
was within USP requirements recognized by FDA, and (3) ten years of independent
EMA sampling of products obtained at wholesalers and pharmacies across the EU
confirmed compliance (n = 43). CONCLUSIONS: The study by Carter and Heinemann
utilized an LC-MS technique, which has not been validated for the quantification
of insulin in pharmaceutical preparations. It appears likely that their findings
are the result of the method utilized and not due to decreased insulin content in
samples. However, recognizing the importance of maintaining Insulin content from
production to the patient, Novo Nordisk supports continued evaluation of insulin
distributed to pharmacies and patients utilizing validated techniques compliant
with international pharmacopeias.
PMID- 29952656
TI - Preventing war and promoting peace: a guide for health professionals.
PMID- 29952655
TI - A Multicenter, Cross-Sectional Assessment of Otolaryngology Knowledge Among
Primary Care Trainees.
AB - OBJECTIVES: (1) Identify knowledge deficits in this cohort regarding basic
conditions treated by an otolaryngologist. (2) Determine the training needs of
these physicians regarding the care of the head and neck patient. METHODS: This
cross-sectional assessment used a 10-question, multiple-choice assessment
administered to medical students and resident physicians at the University of
California, Davis, University of California, San Francisco, and University of
West Virginia in the departments of emergency medicine, family medicine, internal
medicine, and otolaryngology. RESULTS: The otolaryngology cohort scored an
average of 93%, while all others scored 56%. There was no statistical difference
in the results between fourth-year medical students and non-otolaryngology
residents of any year. Only 16% of the primary care providers and students
assessed felt comfortable with these conditions, and 86% (321/372) of the
respondents desired increased education on these topics. CONCLUSION: This study
identified significant knowledge gaps among non-otolaryngologists in the
diagnosis and treatment of basic head and neck conditions. As a specialty, a
greater focus should be placed on improving the familiarity of our primary care
colleagues on these conditions.
PMID- 29952657
TI - Medication related osteonecrosis of the jaw in osteoporotic vs oncologic patients
quantifying radiographic appearance and relationship to clinical findings.
AB - OBJECTIVES: To explore whether differences exist in the clinical and radiographic
presentation of oncologic vs osteoporotic patients with medication-related
osteonecrosis of the jaw (MRONJ). METHODS: We retrospectively assessed panoramic
radiographs and CBCT examinations of 70 MRONJ patients receiving antiresorptive
medications for the management of either osteoporosis or bone malignancy.
Radiographic features of MRONJ were documented and categorized according to
severity. A composite radiographic index (CRI) was constructed to account for the
heterogeneity in radiographic manifestations of MRONJ and further stratify extent
of osseous changes. RESULTS: Patients with osteoporosis were mostly older females
and presented more frequently with Stage 2 MRONJ, while patients with malignancy
were equally distributed between males and females, and presented mostly with
Stage 1 MRONJ. Most MRONJ lesions in oncologic patients occurred in the mandible,
whereas the maxilla and mandible were equally affected in osteoporotic patients.
Patients with minimal radiographic changes (low CRI score) often presented with
MRONJ in dentate areas, while most patients in medium and high CRI groups
presented with MRONJ after recent tooth extraction. The low CRI group consisted
of primarily oncologic patients, while osteoporotic vs oncologic patients were
divided more evenly in the other CRI groups (p = 0.083). While CRI scores
increased with clinical staging, a Spearman's rank correlation coefficient of
0.49 suggests that clinical appearance does not reliably predict osseous changes.
CONCLUSIONS: Our data identify differences in the MRONJ appearance of patients
with osteoporosis vs malignancy and emphasize the significance of detailed
radiographic assessment, in addition to the clinical appearance, in
characterizing the osseous changes of the disease.
PMID- 29952658
TI - Training Monitoring Engagement: An Evidence-Based Approach in Elite Sport.
AB - PURPOSE: Poor athlete buy-in and adherence to training monitoring systems (TMS)
can be problematic in elite sport. This is a significant issue, as failure to
record, interpret, and respond appropriately to negative changes in athlete
wellbeing and training status may result in undesirable consequences, such as
maladaptation and/or underperformance. This study examined the perceptions of
elite athletes to their TMS, and their primary reasons for non-completion.
METHODS: Nine national team sprint athletes participated in semi-structured
interviews on their perceptions of their TMS. Interview data was analysed
qualitatively, based on grounded theory, and TMS adherence information was
collected. RESULTS: Thematic analysis showed that athletes reported their main
reason for poor buy-in to TMS was a lack of feedback on their monitoring data
from key staff. Further, training modifications made in response to meaningful
changes in monitoring data were sometimes perceived to be disproportionate,
resulting in dishonest reporting practices. CONCLUSIONS: Perceptions of opaque or
unfair decision-making on training programme modifications and insufficient
feedback were the primary causes for poor athlete TMS adherence. Supporting TMS
implementation with a behavioural change model that targets problem areas could
improve buy-in and enable limited resources to be appropriately directed.
PMID- 29952659
TI - Treatment of inflammatory myopathies.
AB - INTRODUCTION: The idiopathic inflammatory myopathies (IIM) dermatomyositis (DM)
and polymyositis (PM) are chronic diseases affecting the striated muscles with
variable involvement of other organs. Glucocorticoids are considered the
cornerstone of treatment, but some patients require adjunctive immunosuppressive
agents because of insufficient response to glucocorticoids, flares upon
glucocorticoid tapering, or glucocorticoid-related adverse events. Areas covered:
The aim of this article was to review (PubMed search until February 2018) the
evidence on established and new therapies derived from randomized controlled
trials (RCTs) on adult DM and PM. In addition, key data from open-label trials,
case reports, and abstracts were included where data from RCT were lacking.
Expert commentary: Numerous synthetic and biological immunosuppressive agents are
currently available to treat the IIM, sometimes in combination. The choice of the
specific medication in the individual patient depends upon the disease phenotype
and patient's characteristics. Exercise improves muscle performance without
causing disease flares and should be an integral part of the treatment of the
IIM. Prompt diagnosis and treatment can lead to better outcome.
PMID- 29952660
TI - Successful application of a single warming protocol for embryos cryopreserved by
either slow freezing or vitrification techniques.
AB - : The aim of this study was to evaluate the feasibility and efficiency of using a
sucrose gradient-based warming protocol as a universal warming approach on human
cleavage stage embryos. Between January 2013 and November 2014, a total of 118
warming cycles were performed on 705 embryos which had previously been
cryopreserved/thawed by slow freezing protocols or cryopreserved by slow freezing
and warmed by vitrification thaw solution. Clinical outcomes have been
retrospectively analyzed depending on cryopreservation and warming techniques
used, embryo viability, day of cryopreservation, clinical pregnancy,
implantation, and live birth rate. Results indicate that, the use of the
vitrification warming protocol for warming after slow freezing results in
comparable post-warming survival (71.6% and 71.1%; p = 0.890). Higher clinical
pregnancy, implantation, and live birth rates were obtained in the cryopreserved
embryos by slow freezing and warmed by vitrification group in comparison to the
cryopreserved/thawed by slow freezing protocols group but the results did not
show statistically significant differences between groups (p > 0.05). These
results indicate that such an approach can eliminate the need to search for a
brand-dependent product, as well as case-dependent hands-on planning. Further
research that evaluates the effectiveness of this approach on a larger case
series is underway. ABBREVIATIONS: CPA: concentrated cryoprotective agent; COH:
controlled ovarian stimulation; FET: frozen embryo transfer; HSG:
hysterosalpingogram; mHTF: modified human tubal medium; SSM: single step media;
SSS: synthetic serum substitute; TV-USG: transvaginal ultrasound.
PMID- 29952661
TI - Association between HLA-G 14bp Gene Polymorphism and Serum sHLA-G Protein
Concentrations in Preeclamptic Patients and Normal Pregnant Women.
AB - BACKGROUND: Preeclampsia (PE) is a multisystem syndrome that is a primary source
of fetal-maternal morbidity and mortality. Human leukocyte antigen-G (HLA-G) is a
nonclassical Major histocompatibility complex (MHC) class-Ib molecule expressed
on the extravillous trophoblast and seems to have immunomodulatory functions
during pregnancy. The purpose of our study was to investigate whether HLA-G may
be a vital marker in the modulation of the pregnancy. METHODS: In this case
control study, a number of 150 healthy pregnant women and 150 patients with PE
had been genotyped for the 14 base-pair (bp) insertion/deletion polymorphism in
exon 8 of the HLA-G gene, and the serum level of soluble HLA-G (sHLA-G) protein
was measured using the enzyme-linked immunosorbent assay. RESULTS: Data showed
that the PE syndrome was not related to the HLA-G 14 bp genotype. But, the serum
level of sHLA-G in PE patients was significantly lower than that in healthy
pregnant women in the third trimester (11.74 and 24.48 U/ml, respectively, p <
0.001). However, no significant association was observed between the HLA-G 14 bp
genotype and serum sHLA-G level. CONCLUSION: Our results demonstrate that
measurement of sHLA-G protein level may be helpful as a primary diagnosis for the
pathogenesis of PE. Overall, this study suggests that the association between HLA
G 14 bp polymorphism and serum sHLA-G level in different ethnic populations of PE
should be taken into consideration.
PMID- 29952662
TI - Polarized vs. High Intensity Multimodal Training in Recreational Runners.
AB - PURPOSE: This study longitudinally compared changes in running performance (5-km
TT) and fitness (VO2max, body composition) between polarized training and
CrossFit Endurance(c) in recreational runners. METHODS: Participants (N=21)
completed 12 weeks of CrossFit Endurance (CFE) or polarized endurance training
(POL). Both groups trained 5 d.wk-1. POL ran 5 d.wk-1 while CFE ran 3 d.wk-1 and
performed CrossFit(c) 3 d.wk-1 (run + CF 1 d.wk-1). Intensity was classified as
low, moderate, or high (Zone 1, 2, or 3) according to ventilatory thresholds. POL
was prescribed greater volume (295+/-67 min.wk-1), distributed as 85/5/10% in
Z1/Z2/Z3. CFE emphasized a lower volume (110+/-18 min.wk-1) distribution of
48/8/44%. RESULTS: POL ran 283+/-75.9 min.wk-1 and 47.3+/-11.6 km.wk-1, both
exceeding the 117+/-32.2 min.wk-1 and 19.3+/-7.17 km.wk-1 in CFE (p<0.001). The
POL distribution (74/11/15%) had greater total and percent Z1 (p<0.001) than CFE
(46/15/39%), which featured higher percent Z3 (p<0.001). TT improved -93.8+/
40.4s (-6.21+/-2.16%) in POL (p<0.001) and -84.2+/-65.7s (-5.49+/-3.56%) in CFE
(p=0.001). Body composition improved by -2.45+/-2.59 %fat in POL (p=0.02) and
2.62+/-2.53% CFE (p=0.04). The magnitude of improvement was not different between
groups for TT (p=0.79) or BC (p=0.88). Both groups increased VO2 max (p<=0.01),
but with larger magnitude (p=0.04, d=0.85) in POL (4.3+/-3.6 ml.kg.min-1) than
CFE (1.78+/-1.9 ml.kg.min-1). CONCLUSIONS: Recreational runners achieved similar
improvement in 5-km performance and body composition through polarized training
or CFE, but POL yielded a greater increase in VO2 max. Extrapolation to longer
distances requires additional research.
PMID- 29952664
TI - Advance in oral delivery systems for therapeutic protein.
AB - Oral delivery is the most common method of drug administration with high safety
and good compliance for patients. However, delivering therapeutic proteins to the
target site via oral route involves tremendous challenge due to unfavourable
conditions like biochemical barrier, mucus barrier and epithelial barriers.
According to the functional differences of various protein drug delivery systems,
the recent advances in pH responsive polymer-based drug delivery system,
mucoadhesive polymer-based drug delivery system, absorption enhancers-based drug
delivery system and composite polymer-based delivery system all were briefly
summarised in this review, which not only clarified the clinic potential of these
novel drug delivery systems, but also described the way for increasing oral
bioavailability of therapeutic protein.
PMID- 29952663
TI - Prospective study comparing Xalatan(r) eye drops and two similar generics as to
the efficacy and safety profile.
AB - PURPOSE: To evaluate the efficacy and safety between two generic prostaglandins
Lataz-Xalaprost (Greece) and the corresponding original drops (Xalatan(r)).
MATERIAL AND METHODS: In this prospective randomized study, 60 patients diagnosed
with open-angle glaucoma or ocular hypertension were enrolled, who had never
received antiglaucoma treatment. Subjects were divided randomly into three groups
(Xalatan, Lataz, and Xalaprost groups) and they were studied over 16 weeks. At
each visit, the mean applanation tonometry values and tear break-up time were
measured. The Ocular Surface Disease Index questionnaire was used to evaluate
patient's symptoms. RESULTS: There was a statistically significant difference (p
< 0.001) in the mean values of the intraocular pressure between the baseline and
the last visit (Xalatan group: from 23.11 +/- 1.61 mmHg to 15.81 +/- 1.22 mmHg,
Lataz group: from 23.26 +/- 1.33 mmHg to 15.80 +/- 1.47 mmHg, and Xalaprost
group: from 23.08 +/- 1.45 mmHg to 16.08 +/- 1.38 mmHg). Both generic eye drops
showed mean percentage intraocular pressure reduction comparable to the standards
of prostaglandin analogues (Xalatan: 31.57%, Lataz: 32.06%, and Xalaprost:
30.34%). Xalatan reduced the tear break-up time less, followed by Lataz and then
by Xalaprost (Xalatan: from 8.5 to 8 s, Lataz: from 8.2 to 7.4 s, and Xalaprost:
from 8.7 to 7.7 s). Xalatan presented the best safety profile, followed by Lataz
and least was Xalaprost, according to Ocular Surface Disease Index
questionnaire's results. CONCLUSION: No significant difference was recorded in
the effectiveness of each generic prostaglandin compared to the original.
Furthermore, no patient had to change medication. The differences that arose in
the safety profile of the three eye drops suggest a prompt closer initial
monitoring of patients who are administered generic eye drops.
PMID- 29952665
TI - Is Guardian Permission a Barrier to Online Sexual Health Research Among
Adolescent Males Interested in Sex With Males?
AB - Institutional review boards (IRBs) that refuse to grant waivers of guardian
permission may hinder research to inform needed online sexual health
interventions for adolescent males interested in sex with males (AMSM).
Information on the challenges of obtaining (or waiving) guardian permission is
imperative. In June and July 2017, AMSM (N = 206; ages 14 to 17) in the United
States completed an online survey on sexual behaviors, sexually explicit media
use, and sexual education exposure/needs. A mixed-methods approach assessed
attitudes toward guardian permission for the current survey and future online
sexual health intervention research. Logistic regression models assessed
differences by "outness" to a guardian. A framework matrix analysis was conducted
to summarize, then aggregate, qualitative responses. Findings indicated that most
AMSM would not participate if guardian permission was required (current: 83%;
future: 87%). Youth who were not out were more likely to say they would not
participate (current: adjusted odds ratio [AOR] = 2.8, 95% confidence interval
[CI]: 1.2 to 6.8); future: AOR = 4.7, 95% CI: 1.6 to 13.5). Participants reported
that guardian permission would be an invasion of their privacy, lead to
involuntary outing, and endanger participants. Overall, guardian permission
appears to be a barrier to AMSM participation in online sexual health research.
Investigators and IRBs should consider alternative practices and policies to
facilitate such research.
PMID- 29952666
TI - Foot Width Changes Following Hallux Valgus Surgery.
AB - BACKGROUND:: Hallux valgus (HV) adversely affects quality of life. Patients
frequently express concerns regarding postoperative foot appearance, foot width
and footwear anticipations. However, only scarce data are available regarding
postoperative foot width. MATERIALS AND METHODS:: Seventy-one cases with moderate
to severe HV treated with scarf osteotomy were included. The average age was 55.7
years (range, 20-76), with average follow-up of 20.7 months (range, 6-96).
Patients' medical records were reviewed for demographic, operative, and
radiographic data. Foot width was assessed radiographically by measuring both
bone (distance between the first and fifth metatarsal heads) and soft tissue
width (maximal distance of the soft tissue outline). RESULTS:: Preoperative HV
deformity (mean hallux valgus angle [HVA] 35.8 degrees, intermetatarsal angle
[IMA] 14.1 degrees, and distal metatarsal articular angle [DMAA] 15.2 degrees)
was successfully corrected (postoperative mean HVA 13.7 degrees, IMA 6.9 degrees,
and DMAA 7.7 degrees). Overall bony foot width was reduced by 5% and soft tissue
foot width by 2%. Further analysis showed that 13 feet (18.3%) had increased
(>5%) bone width, 26 feet (36.6%) with no change (+/-5%), and 32 feet (45.1%) for
which the width decreased (>5%) postoperatively. Angular deformity (HVA, IMA, and
DMAA) showed low correlation with postsurgery foot width. CONCLUSION:: HV surgery
effect on foot width was very limited, overall reducing foot width by 2%.
Furthermore, in only about half of the patients, the postoperative foot width
decreased, regardless of angular deformity magnitude. Patients with the widest
feet had a decrease in foot width following surgery, whereas patients with the
narrowest feet had an increase in foot width. LEVEL OF EVIDENCE:: Level III,
comparative series.
PMID- 29952667
TI - The economic burden of preventable adverse drug reactions: a systematic review of
observational studies.
AB - INTRODUCTION: Adverse drug reactions (ADRs) are an important cause of morbidity
and mortality worldwide. They are associated with healthcare costs due to
hospital admissions or prolonged length of stay, as well as additional
interventions. The aim of this study was to conduct a systematic review of
observational studies to evaluate the economic impact of preventable ADRs. Areas
covered: Published observational research investigating the cost of preventable
ADRs in Western countries (limited to the USA and European countries). Expert
opinion: Several reviews have been carried out in the field of the ADR
epidemiology but fewer reviews have investigated the economic impact of ADRs, and
at the time of writing, none has focused on preventable ADRs. The reason why
future research should focus on the costs of preventable ADRs is that both the
costs and the negative clinical outcomes are preventable, and as such, are a key
point of public health policy action. Nevertheless, the present review highlights
an important and sobering limitation of published research on the cost of
preventable ADRs, of which the major limitation is the heterogeneity in methods
and in reporting which limit what can be known through the summarizing work of a
systematic review.
PMID- 29952669
TI - Putting the "I" Back in Team.
AB - There is a common expression in sports that "there is no 'I' in team." However,
collectively, there is actually a very important "I" in sport teams-the
individual athlete/player. Each player has his or her own unique characteristics
including physical, physiological, and psychological traits. Due to these unique
characteristics, each player requires individual provision-whether it be an
injury risk profile and targeted prevention strategy or treatment/rehabilitation
for injury, dietary regimen, recovery, or psychological intervention. The aim of
this commentary is to highlight how 4 high-performance teams from various
professional football codes are analyzing individual player data.
PMID- 29952668
TI - Circulating soluble LIGHT/TNFSF14 is increased and associated with IL-8
concentration in chronic spontaneous urticaria.
AB - LIGHT (homologous to lymphotoxins, exhibiting inducible expression, and competing
with herpes simplex virus (HSV) glycoprotein D for herpes virus entry mediator
(HVEM), a receptor expressed by T lymphocytes) has been involved in various
autoimmune and inflammatory disorders. LIGHT induces the expression of
interleukin-8 (IL-8), which is up-regulated in chronic spontaneous urticaria
(CSU). To determine circulating soluble LIGHT concentration and its relationship
with IL-8 concentration in patients with CSU. Concentrations of LIGHT, IL-8, and
C-reactive protein (CRP) were determined in plasma or serum of CSU patients by an
enzyme-linked immunosorbent assay. LIGHT plasma concentration was significantly
higher in moderate-severe CSU patients as compared with the healthy subjects, but
not with mild CSU patients. There were significant correlations between increased
LIGHT and IL-8 concentrations, but not with increased CRP in CSU patients.
Enhanced plasma concentrations of soluble LIGHT and its association with IL-8
concentration suggest the role of LIGHT in systemic inflammatory activation in
CSU patients. We hypothesize that LIGHT-mediated immune-inflammatory response
plays a role in severe phenotypes of the disease.
PMID- 29952670
TI - Evidence of the Exercise Hypogonadal Male Condition at the 2011 Kona Ironman
World Championships.
AB - PURPOSE: Prior research has illustrated that high volumes of aerobic exercise
result in a reduction in basal concentrations of testosterone in men. These prior
studies have mostly been conducted on recreational runners and identified reduced
testosterone, but not concentrations low enough to be considered pathological.
Therefore, the purpose of this study is to assess the basal concentrations of
testosterone and cortisol in elite triathletes, as well as assess the impact of a
World Championship race on the acute responses of these hormones. METHODS: 22 men
(Age: 40.6 +/- 11.5 yrs; Height: 179 +/- 6 cm; Weight: 77.0 +/- 7.0 kg) who
participated in the 2011 Ironman World Championships served as subjects. Resting
blood samples were taken 2-4 days prior (BL), as well as immediately (IP), 1 day
(D1) and 2 days (D2) following the event, and were later analyzed for total
testosterone and cortisol concentrations. RESULTS: At BL, of the 22 subjects, 9
men had a normal testosterone concentration, while 9 men fell within a 'grey
zone' and 4 other men demonstrated concentrations suggestive of deficiency.
Testosterone was significantly lower than BL at D1 (95% CI=0.10-0.34, P<0.001,
ES=0.53) and D2 (95% CI=0.01-0.21, P=0.034, ES=0.35). Cortisol was significantly
different from baseline at IP (95% CI=1.07-0.83, P<0.001, ES=8.0). There were
significant correlations between time and age (R = 0.68, P=0.001) as well as
baseline testosterone and cortisol (R=0.51, P=0.015). CONCLUSIONS: Elite ultra
endurance athletes may demonstrate not only reduced testosterone, but sometimes
clinically low concentrations that could be indicative of androgen deficiency.
PMID- 29952671
TI - The dribbling agility test as a potential tool for evaluating the dribbling skill
in young soccer players.
AB - The present study examined the construct validity and reliability of a new
dribbling agility test (DAT) that incorporates reactive agility and multiple
change of direction. To check its' validity, (a) DAT was performed by four groups
(under 10, under 12, under 14 and under 16 yrs) of young soccer players (n = 125
in each group) and (b) a regression analysis was conducted to define the best DAT
predictors. The reliability of DAT was assessed with repeated measurements. This
test can differentiate the dribbling skill between groups (p < 0.01).
Furthermore, 68% of the observed variance in DAT was explained by zigzag
dribbling test, Illinois agility test, reaction time and running speed. The test
retest reliability was high in all groups (ICC = 0.77 - 0.90, p < 0.01). It was
concluded that DAT can be a potential tool to evaluate the dribbling performance
in young soccer players.
PMID- 29952672
TI - Effects of Complex Strength Training Program on Athletic Performance of Junior
Female Handball Players.
AB - PURPOSE: This study analyzed the effects of complex strength training on the
explosive muscular performance of junior female handball players. METHODS:
Subjects were arbitrarily divided between an experimental group (n=14) and a
control group (n=14). Training sessions and matches were performed together, but
during the 10-week intervention, the experimental group replaced a part of the
regular regimen by complex strength training. Measures assessed in both groups
before and after the intervention included: running times over 5, 10, 20 and 30 m
, change of direction tests [T-half agility test and modified Illinois test],
repeated shuttle sprint ability and repeated changes of direction tests, jumping
[squat, counter-movement, counter-movement with aimed arms and five-jump tests],
static and dynamic balance, back extensor strength and 1RM half-squat. RESULTS:
The intervention yielded increases in sprint (10 m: 11.7%), change of direction
performance (T-half: 5.1%; modified Illinois: 4.2%), jumping (squat p<0.01; 19%;
countermovement p<0.01; 20.3%; countermovement aimed arms p<0.01; 19.3%; 5-jump
p<0.05; 15.2%), and one of 4 repeated sprint scores (best time, p<0.05; 5.9%).
However, Repeated sprint T-test and balance scores were unchanged. CONCLUSIONS:
Complex srength training develops abilities important to handball performance.
PMID- 29952673
TI - Reconstitution of W' in Recovery Slows With Repeated Bouts of Maximal Exercise.
AB - Purpose This study examined the partial reconstitution of the work capacity above
critical power (W') following successive bouts of maximal exercise using a new
repeated ramp test (RRT), against which the fit of an existing W' balance (W'bal)
prediction model was tested. Methods Twenty active adults, consisting of trained
cyclists (n = 9; age 43 +/- 15 years; VO2max 61.9 +/- 8.5 mL?kg?min-1) and
untrained (n = 11; age 36 +/- 15 years; VO2max 52.4 +/- 5.8 mL?kg?min-1)
performed two tests 2-4 days apart, consisting of three incremental ramps (20
W?min-1) to exhaustion interspersed with 2-min recoveries. Results Intra-trial
differences between recoveries demonstrated significant reductions in the amount
of W' reconstituted for the group and both sub-sets (p < 0.05). The observed
minimal detectable changes of 475 J (first recovery) and 368 J (second recovery)
can be used to monitor changes in the rate of W' reconstitution in individual
trained cyclists. Inter-trial relative reliability of W' reconstitution was
evaluated by intraclass correlation coefficients for the group (>= 0.859);
trained (>= 0.940) and untrained (>= 0.768) sub-sets. Absolute reliability was
evaluated with typical error (TE) and coefficient of variation (CV) for the group
(TE <= 559 J; CV <= 9.2%), trained (TE <= 301 J; CV <= 4.7%), and untrained (TE
<= 720 J; CV <= 12.4%). Conclusions The reconstitution of W' is subject to a
fatiguing effect hitherto unaccounted for in W'bal prediction models.
Furthermore, the W'bal model did not provide a good fit for the RRT, which itself
proved to be a reliable test protocol.
PMID- 29952674
TI - Measurement Properties of an Adductor Strength Assessment System in Professional
Australian Footballers.
AB - PURPOSE: To examine the measurement properties of an adductor strength assessment
system in professional Australian footballers. METHODS: Observational,
longitudinal design. Test-retest reliability data were collected from 18
professional Australian footballers from one club on the same day during the 2017
AFL competition. Week-to-week variation data were collected on 45 professional
Australian footballers from one club during the same season at 48, 72 and 120 h
post-match (rounds 1-23). Players lay beneath a GroinBar Hip Strength Testing
System in supine position with their knee joint at an angle of 60 degrees. Force
(N) was extracted for left and right limbs of each player and a pain score from 0
10 (0=no pain, 10=maximum pain) was provided. Coefficient of variation (CV) and
smallest worthwhile change (SWC) were calculated on test-retest data. Signal-to
noise ratio (SNR) was calculated for each major time point. Mean difference
between force scores in a subgroup of players with and without groin pain (n=18)
were collected as evidence of construct validity for the system. RESULTS: Test CV
was 6.3% [4.9, 9.0]. CV exceeded the SWC on both limbs. Intraclass coefficient
(ICC) was 0.94. SNR ranged from 1.6 and 2.6 on average for 48, 72 and 120 h post
match. Groin pain had a very likely moderate negative effect on adductor strength
(ES: 0.41). CONCLUSIONS: The system possesses greater measurement precision to
dynamometry and sphygmomanometer adductor strength assessment methods in
professional Australian footballers. Increased groin pain reduced groin squeeze
force production. Practitioners may interpret changes exceeding 6.3% in adductor
strength as real.
PMID- 29952675
TI - The Effects of Chronic Cold Water Immersion in Elite Rugby Players.
AB - PURPOSE: While the acute effects of cold water immersion (CWI) have been widely
investigated, research analysing the effects of CWI over a chronic period in
highly-trained athletes is scarce. The aim of this study was to investigate the
effects of CWI during an intense three week pre-season phase in elite rugby
athletes. METHODS: Twenty-three elite male rugby union athletes were randomized
to either CWI (10 min at 10 oC, n = 10) or a passive recovery control (CON, n =
12) during three-weeks of high volume training. Athletes were exposed to either
CWI or CON, after each training day (12 days in total). Running loads,
conditioning and gym sessions were kept the same between groups. Measures of
countermovement jump (CMJ), perceived muscle soreness and wellness were obtained
twice a week, and saliva samples for determining cortisol and interleukin-6 (IL
6) were collected once per week. RESULTS: Although no significant differences
were observed between CWI and CON for any measure, CWI resulted in lower fatigue
markers throughout the study, as demonstrated by the moderate effects on muscle
soreness (d = 0.58 to 0.91) and IL-6 (d = -0.83), and the small effects (d = 0.23
to 0.38) on CMJ in comparison to CON. CONCLUSIONS: The results from this study
demonstrate that CWI may provide some beneficial effect by reducing fatigue and
soreness during an intense three week training phase in elite rugby athletes.
PMID- 29952677
TI - Psychometric evaluation of the Finnish translation of the assessment of
communication and interaction skills (ACIS-FI).
AB - BACKGROUND: The Model of Human Occupation (MOHO) is a widely used conceptual
practice model in Finland. Therefore, Finnish translations of valid and reliable
MOHO assessments are needed. OBJECTIVE: The primary objective of this study was
to examine the psychometric properties of the Finnish translation of the
Assessment of Communication and Interaction Skills (ACIS-FI) using the many-facet
Rasch model approach. METHODS AND MATERIALS: Twenty-eight occupational therapists
completed an in-person training workshop on the ACIS-FI and participated as
raters in this study. One hundred and forty-eight clients were rated using the
ACIS-FI. Rating scale functioning, unidimensionality, person validity and rater
severity, item targeting, and item and person separation statistics were
examined. RESULTS: The rating scales demonstrated adequate functioning; the
rating category 'deficit' was infrequently adopted by the raters. The ACIS-FI had
satisfactory construct validity, as confirmed by all items exhibiting
unidimensionality within a single construct (i.e. communication and interaction
skills), and appropriate item fit. Validity was further confirmed through low
person misfit (6%) and low rater misfit (3.6%). No ceiling or floor effects were
found. The ACIS-FI was able to separate clients into four levels of communication
and interaction skills. CONCLUSIONS: This study offers evidence for the validity
of the ACIS-FI as a measure of communication and interaction skills in
occupational therapy. SIGNIFICANCE: The ACIS-FI offers Finnish practitioners and
researchers a valid tool to measure communication and interactions skills that is
theoretically grounded in the MOHO.
PMID- 29952676
TI - Galangin, a dietary flavonoid, ameliorates hyperglycaemia and lipid abnormalities
in rats with streptozotocin-induced hyperglycaemia.
AB - CONTEXT: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum
Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and
anticancer properties, without side effects. The effects of galangin on
hyperglycaemia and lipid abnormalities are not known. OBJECTIVE: To elucidate the
effectiveness of galangin on hyperglycaemia-associated complications and lipid
changes in rats with streptozotocin (STZ)-induced hyperglycaemia. MATERIALS AND
METHODS: Diabetes was induced in adult Wistar rats by administering 40 mg/kg of
STZ. In our previous study, galangin had no toxicity at concentrations up to 320
mg/kg. Therefore three doses of galangin (4, 8 or 16 mg/kg BW) or glibenclamide
(600 ug/kg BW) were administered daily to diabetic rats orally for 45 days.
RESULTS: Diabetic rats showed a significant (p < 0.05) increased levels of plasma
glucose (281.10 mg/dL) and decreased levels of insulin (6.01 MUU/mL).
Additionally, diabetic rats showed a significant (p < 0.05) increased levels of
plasma lipid profiles such as total cholesterol (149.05 mg/dL), triglycerides
(143.28 mg/dL), free fatty acids (139.37 mg/dL), phospholipids (127.53 mg/dL),
plasma low-density lipoprotein-cholesterol (98.72 mg/dL), plasma very low-density
lipoprotein-cholesterol (28.65 mg/dL), and significant (p < 0.05) decreased in
plasma high-density lipoprotein-cholesterol (21.68 mg/dL). When galangin was
administered to the hyperglycaemic rats, plasma glucose and insulin levels and
lipid profiles reverted to levels similar to those in healthy control rats.
DISCUSSION AND CONCLUSIONS: Administration of galangin reduced hyperlipidaemia
related to the risk of diabetic complications and could be beneficial for
diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action
for improving hyperglycaemic-associated lipid abnormalities is needed.
PMID- 29952678
TI - Predicting Trail Running Performance With Laboratory Exercise Tests and Field
Based Results.
AB - PURPOSE: Trail running is a complex sport and performance prediction is
challenging. Our aim is to evaluate three standard laboratory exercise tests in
trail runners and correlate measurements to the race time of a trail competition
evaluating its predictive power. METHODS: Nine competitive male trail runners
(mean age 31+/-5.8 years) completed three different laboratory exercise tests
(step, ramp and trail test) for determination of VO2max, vVO2max, ventilatory and
lactate thresholds (LT), mechanical power output and running economy (RE) ,
followed by a 31km trail race. Runners previously participated in the same race
(previous year) and finished in the top 2%. Finishing times (dependent value)
were tested in multiple regression analysis with different independent value
combinations. RESULTS: Linear regression analysis revealed that variables
measured during step and ramp test significantly predicted performance. Step test
variables (speed at individual anaerobic threshold (IAT) 16.4+/-1.7 km/h and RE
12km/h (%VO 2 max) 65.6+/-5.4%) showed the highest performance prediction
(R2=0.651; F(2,6)=5.60; P=.043), followed by the ramp test (vVO2max 20.3+/
1.3km/h; R2= 0.477; F(1,7)=6.39; P=.04) and trail test (Pmax 3.9+/-0.5 W/kg,
VO2max 63.0+/-4.8 ml O2 .kg-1.min-1, vVT1 11.9+/-0.7 km/h; R2=0.68; F(3,5)=3.52;
P =.11). Adding race time from the preceding year to the step test improved the
predictive power of the model (R2=0.988; F(3,5)=66.51; P<.001). CONCLUSION: The
graded exercise test (VO2max, IAT and RE) most accurately predicted a 31.1km
trail running performance. Combining submaximal intensities (IAT and RE) with the
previous years race time of that specific event increased the predictive power of
the model to 99%.
PMID- 29952679
TI - Utility of calcium phosphate cement cranioplasty following supraorbital approach
for tumor resection.
AB - OBJECTIVE: We have previously documented the utility of calcium phosphate cement
cranioplasty following retromastoid craniectomy. In this study, we aimed to
demonstrate its efficacy following a supraorbital approach for tumor resection.
METHODS: A retrospective analysis of a prospectively maintained database was
conducted of eight patients (7 female, 1 male) with anterior cranial fossa
meningiomas resected via a supraorbital approach followed by cranioplasty
involving adjunctive or sole use of calcium phosphate cement. RESULTS:
Cranioplasty was achieved in all patients. No patient developed an incisional
leak. The cohort had a mean follow-up of approximately 3.1 months (range: 0.5-7
months) in which time no further complications were noted. No patients developed
post-surgical infections. CONCLUSION: In our experience, a low incidence of
infection or CSF leaks has been noted after the use of calcium phosphate cement
retromastoid cranioplasty. Extending this technique to supraorbital craniotomies
may minimize incisional CSF leak.
PMID- 29952680
TI - Antigenotoxic potential of boron nitride nanotubes.
AB - Boron and boron nitride nanotubes (BNNTs) are increasingly used in different
industrial fields and, potentially, in some biomedical areas. As occurs with
other nanomaterials (NMs), to increase our knowledge on their potential health
hazards is a priority. Although in vitro approaches are a routine in getting
biological information on the biological effects of NMs, the use of simple in
vivo model organisms is receiving an increased interest. In this context,
Drosophila melanogaster is widely used as a eukaryotic model for the study of the
potential harmful effects associated with various agents, including NMs. The aim
of this study is to provide new data on the potential antioxidant/antigenotoxic
properties of boron and boron nitride nanotubes (BNNTs), as well as on other
biological end-points. Our results show changes in the expression of genes
involved in the antioxidant defense (CAT and SOD), and in those rel0061ted to the
integrity of the intestinal barrier (Duox, Hml, Muc68D, and PPO2), at the highest
exposure doses (5, 10 mM). However, non-relevant toxic or genotoxic effects were
observed. Interestingly, BNNTs and boron significantly reduced the genotoxic
effect of potassium dichromate (PDC), and the intracellular levels of reactive
oxygen species (ROS). This suggest that the observed effects can be linked to the
antioxidant properties of BNNTs and boron. This is the first study reporting
antigenotoxicity/genotoxicity, and gene expression data, in the somatic cells of
D. melanogaster larvae for BNNTs.
PMID- 29952681
TI - Development of an isotoxic decision support system integrating genetic markers of
toxicity for the implantation of a rectum spacer.
AB - INTRODUCTION: Previous studies revealed that dose escalated radiotherapy for
prostate cancer patients leads to higher tumor control probabilities (TCP) but
also to higher rectal toxicities. An isotoxic model was developed to maximize the
given dose while controlling the toxicity level. This was applied to analyze the
effect of an implantable rectum spacer (IRS) and extended with a genetic test of
normal tissue radio-sensitivity. A virtual IRS (V-IRS) was tested using this
method. We hypothesized that the patients with increased risk of toxicity would
benefit more from an IRS. MATERIAL AND METHODS: Sixteen localized prostate cancer
patients implanted with an IRS were included in the study. Treatment planning was
performed on computed tomography (CT) images before and after the placement of
the IRS and with a V-IRS. The normal tissue complication probability (NTCP) was
calculated using a QUANTEC reviewed model for Grade > =2 late rectal bleeding and
the number of fractions of the plans were adjusted until the NTCP value was under
5%. The resulting treatment plans were used to calculate the TCP before and after
placement of an IRS. This was extended by adding the effect of two published
genetic single nucleotide polymorphisms (SNP's) for late rectal bleeding.
RESULTS: The median TCP resulting from the optimized plans in patients before the
IRS was 75.1% [32.6-90.5%]. With IRS, the median TCP is significantly higher:
98.9% [80.8-99.9%] (p < .01). The difference in TCP between the V-IRS and the
real IRS was 1.8% [0.0-18.0%]. Placing an IRS in the patients with SNP's improved
the TCP from 49.0% [16.1-80.8%] and 48.9% [16.0-72.8%] to 96.3% [67.0-99.5%] and
90.1% [49.0-99.5%] (p < .01) respectively for either SNP. CONCLUSION: This study
was a proof-of-concept for an isotoxic model with genetic biomarkers with a V-IRS
as a multifactorial decision support system for the decision of a placement of an
IRS.
PMID- 29952682
TI - Radiation-induced damage to lacrimal glands: an ultrastructural study in Sprague
Dawley rats.
AB - Injury to lacrimal glands represents a major health problem after radiation
therapy of the head and neck malignancies. Accordingly, this study aimed to
investigate significant ultrastructural changes of lacrimal glands and some of
their underlying mechanisms following the exposure to different fractionated
doses of irradiation. In this study, 28 Sprague Dawley (SD) rats were assigned to
four groups (seven rats each): Group I acted as control and received no
irradiation. Groups II-IV received fractionated irradiation of 5 Gy (100
cGy/fraction daily for 5 days), 9 Gy (300 cGy/fraction daily for 3 days), and 20
Gy (one fraction), respectively. One month after the experiment, examination of
lacrimal glands with transmission electron microscopy (TEM) demonstrated dose
dependent ultrastructural changes in the lacrimal acinar and intralobular ductal
epithelial cells. In the acinar cells, there were swollen rough endoplasmic
reticulum, irregularly shaped nuclei with chromatin condensation, mitochondrial
damage, and retention of secretory granules. Intaralobular ductal epithelial
cells showed loss of surface microvilli and damage to mitochondria. In addition
to the potential direct effects of irradiation on lacrimal acinar and
intralobular ductal epithelial cells, damage to blood vessels and nerve endings
seemed to mediate some of the underlying mechanisms of these irradiation-induced
ultrastructural changes. In conclusion, using TEM reveals that lacrimal gland is
highly sensitive to even small doses of irradiation therapy; in addition,
swelling of rough endoplasmic reticulum and aberrant nuclei are the most
encountered structural changes. Damage to blood vessels and nerve endings might
mediate some of the underlying mechanisms of irradiation-induced secondary injury
in lacrimal glands.
PMID- 29952683
TI - Exercise in Motor Development Positions. What Happens with the Activity of
Antagonist Muscle Pairs? Pilot Study.
AB - CONTEXT: Exercises in motor development positions are employed in order to
activate correct muscular patterns but the effects on the activity of antagonist
muscle pairs remain unknown. OBJECTIVES: To determine the effect of using
exercises in motor development positions on the activity of antagonist muscle
pairs. Another aim was to analyze if introducing some facilitators modifies the
muscle activity in the different studied positions. DESIGN: Controlled laboratory
study using a single-group repeated measures design. PATIENTS: Twenty-one right
handed, healthy adults aged over 41 years (10 males and 11 females). SETTING:
Workers of different departments at Maz Hospital. INTERVENTION: Surface
electromyography activity of muscle antagonist pairs Upper Trapezius / Lower
Trapezius, Serratus Anterior / Pectoralis Major and External Abdominal Oblique /
Lumbar Paraspinal was measured in three positions: rest (supine decubitus),
reflex turning 1 (RT1) and Modified Vojta's first position (V1stP). MAIN OUTCOME
MEASURES: Primary outcomes were mean normalized RMS (averaged over two
repetitions) of EMG signals of antagonist muscle pairs in the three analyzed
positions. Intraclass correlation coefficients, ICC>0.70 (model 3,2), type
consistency and 95%CI was used to estimate the reliability and as exclusion
criteria of measurements. RESULT: Analyzed positions had a significant effect on
the activity of the muscles P<.001. There was a significant increase in the
activity of the phasic musculature versus its tonic antagonists, except in the
case of the external oblique / lumbar paraspinal in V1stP. Adding possible
facilitators such as gaze, breathing or the combination of both did not show
significant changes in the level of activation of the studied muscle groups.
CONCLUSION: Ontogenetic developmental positions can be used to facilitate and
improve the activation of phasic muscles.
PMID- 29952684
TI - Metabolic risk factors and the incidence and progression of radiographic hand
osteoarthritis: a population-based cohort study.
AB - OBJECTIVE: To determine whether selected metabolic factors are associated with
greater amounts of radiographic hand osteoarthritis (OA) incidence and
progression. METHODS: The study identified 706 adults, aged 50-69 years, with
hand pain and hand radiographs at baseline, from two population-based cohorts.
Metabolic factors (body mass index, hypertension, dyslipidaemia, and diabetes)
were ascertained at baseline by direct measurement and medical records. Analyses
were undertaken following multiple imputation of missing data, and in complete
cases (sensitivity analyses). Multivariable regression models estimated
associations between metabolic factors and two measures of radiographic change at
7 years for all participants, individuals free of baseline radiographic OA, and
in baseline hand OA subsets. Estimates were adjusted for baseline values and
other covariates. RESULTS: The most consistent and strong associations observed
were between the presence of diabetes and the amount of radiographic progression
in individuals with nodal OA [adjusted mean differences in Kellgren-Lawrence
summed score of 4.50 (-0.26, 9.25)], generalized OA [3.27 (-2.89, 9.42)], and
erosive OA [3.05 (-13.56, 19.67)]. The remaining associations were generally weak
or inconsistent, although numbers were limited for analyses of incident
radiographic OA and erosive OA in particular. CONCLUSION: Overall metabolic risk
factors were not independently or collectively associated with greater amounts of
radiographic hand OA incidence or progression over 7 years, but diabetes was
associated with radiographic progression in nodal, and possibly generalized and
erosive OA. Diabetes has previously been associated with prevalent but not
incident hand OA. Further investigation in hand OA subsets using objective
measures accounting for disease duration and control is warranted.
PMID- 29952685
TI - Quercetin promotes gastrointestinal motility and mucin secretion in loperamide
induced constipation of SD rats through regulation of the mAChRs downstream
signal.
AB - CONTEXT: Quercetin (QCT) has been known as a potential therapeutic strategy for
gastrointestinal diseases because it contributes to the stabilization of mast
cells, the prevention of histamine release and modulation of CaCC chloride
channel. OBJECTIVE: We investigated the laxative effect and action mechanism of
QCT in Lop-induced constipation model. MATERIALS AND METHODS: Constipation of SD
rats was induced by subcutaneous injection of loperamide (Lop) (4 mg/kg weight)
in 0.5% Tween 20 twice a day for three days. After 24 h, the constipation group
was further treated with 1* PBS (Lop + Vehicle treated group), 10 mg/kg of QCT
(Lop + LQCT treated group), 20 mg/kg of QCT (Lop + MQCT treated group) or 40
mg/kg QCT (Lop + HQCT treated group) at once. At 24 h after QCT treatment, the
constipation phenotypes were measured and the transverse colon was collected from
SD rats. RESULTS: The gastrointestinal motility, the number of stools and
histological structures were significantly recovered in Lop + QCT treated group
compared with the Lop + Vehicle treated group. Also, above activity of epithelial
cells and smooth muscle cells were regulated by the mRNA expression of the
muscarinic acetylcholine receptors M2 and M3 (mAChR M2 and M3) and some mediators
of their downstream signalling pathway. Finally, laxative effects of QCT on mAChR
signalling pathway were significantly inhibited by the treatment of mAChR
antagonist in primary smooth muscle of rat intestine cells (pRISMCs).
CONCLUSIONS: This study provides the first strong evidence that QCT can be
considered an important candidate for improving chronic constipation induced by
Lop treatment in animal models.
PMID- 29952686
TI - Near infrared spectroscopy confirms recruitment of specific lumbar extensors
through neuromuscular electrical stimulation.
AB - BACKGROUND: Lumbar multifidus impairments are associated with low back pain
(LBP), with sustained impairments thought to contribute to recurrence and
chronicity of pain. Ability to regain muscle function can be challenging. While
neuromuscular electrical stimulation (NMES) may aid in muscle function recovery,
validity of its ability to selectively recruit the lumbar multifidus and provide
adequate dosage for muscle overload has not been demonstrated. Near infrared
spectroscopy (NIRS) can be used to determine muscle selectivity and overload
during NMES and offers advantages over electromyography (EMG), which is affected
by electrical interference. OBJECTIVE: The aim of this study was to determine the
ability of NMES to activate and overload the lumbar multifidus in isolation.
METHODS: EMG and NIRS were collected over the trunk extensors during standardized
movements followed by delivery of NMES in 10 healthy participants. NIRS was used
to determine the ability of NMES to selectively recruit the lumbar multifidus at
the L5 region relative to other trunk extensors. EMG and NIRS data were then
entered into a linear regression model to predict muscle activity during NMES
relative to the standardized movements. RESULTS: There was a significant
correlation (r = 0.81, p < 0.001) between EMG and NIRS in the lumbar multifidus.
There was significantly greater activation of lumbar multifidus compared to
lumbar erector spinae using specific NMES electrode placement (p < 0.001).
CONCLUSION: NMES can preferentially activate lumbar multifidus with potential to
provide a therapeutic overload to these muscles in healthy participants. It may
be a promising intervention for individuals with LBP.
PMID- 29952687
TI - Physiotherapists' experiences with a blended osteoarthritis intervention: a mixed
methods study.
AB - INTRODUCTION: E-Exercise is an effective 12-week blended intervention consisting
of around five face-to-face physiotherapy sessions and a web-based application
for patients with hip/knee osteoarthritis. In order to facilitate effective
implementation of e-Exercise, this study aims to identify physiotherapists'
experiences and determinants related to the usage of e-Exercise. METHODS: An
explanatory sequential mixed methods design embedded in a randomized controlled
trial comparing e-Exercise with usual physiotherapy in patients with hip/knee
osteoarthritis. Usage of e-Exercise was based on recruitment rates of 123
physiotherapists allocated to e-Exercise and objective web-based application
usage data. Experiences and determinants related to e-Exercise usage were
investigated with a questionnaire and clarified with semi-structured interviews.
RESULTS: Of the 123 physiotherapists allocated to e-Exercise, 54 recruited more
than one eligible patient, of whom 10 physiotherapists continued using e-Exercise
after the study period. Physiotherapists had mixed experiences with e-Exercise.
Determinants related to intervention usage were appropriateness, added value,
time, workload, professional autonomy, environmental factors, and financial
consequences. Physiotherapists recommended to improve the ability to tailor e
Exercise to the individual needs of the patient patients' individual needs.
DISCUSSION: Determinants related to the usage of e-Exercise provided valuable
information for the implementation of e-Exercise on broader scale. Most
importantly, the flexibility of e-Exercise needs to be improved. Next, there is a
need for education on how to integrate an online program within physiotherapy.
PMID- 29952688
TI - Does dental agenesis have an impact on OHRQoL of children, adolescents and young
adults? A systematic review.
AB - Dental agenesis (DA) is defined as the congenital absence of teeth and is
considered as the most common dental anomaly. It may cause speech and masticatory
dysfunctions as well as esthetic problems. Its impact on oral health-related
quality of life (OHRQoL) is not fully understood. The aim of the study was to
assess whether DA affects OHRQoL of children, adolescents and young adults. A
broad search was done on databases (Pubmed, Scopus, Web of Science and Virtual
Health Library) using Medical Subject Headings (MeSH) and free terms. Eligibility
criteria for article selection were predetermined and were classified according
to quality assessment and risk of bias. The electronic search produced 178 titles
and abstracts. After excluding duplicate abstracts and applying the eligibility
criteria, three articles were assessed for the final qualitative synthesis. The
three articles were classified as moderate quality and present risk of bias. No
articles were found that had evaluated children and young adults. From the three
articles that were selected, only one was found to have a greater impact in the
adolescent agenesis group with statistical differences in all domains. There is
insufficient evidence available to conclude if DA affects OHRQoL of children,
adolescents and young adults.
PMID- 29952689
TI - Clinical and genetic features of eight Chinese autosomal-dominant optic atrophy
pedigrees with six novel OPA1 pathogenic variants.
AB - BACKGROUND: Autosomal-dominant optic atrophy (ADOA) is one of the most common
types of inherited optic atrophy. We identify OPA1 pathogenic variants and assess
the clinical features of a cohort of Chinese ADOA patients Materials and Methods:
Detailed clinical evaluations were performed and genomic DNA was extracted from
peripheral blood for all the participants. Sanger sequencing was used to analyze
all exons and exon/intron junctions of OPA1 for eight pedigrees. Target exome
capture plus next-generation sequencing (NGS) were applied for one atypical
family with photophobia. Reverse transcription polymerase chain reaction was
carried out to further characterize the mRNA change of selected splicing
alteration. RESULTS: All 17 patients had impaired vision and optic-disk pallor;
however, the clinical severity varied markedly. Two patients complicated with
hearing loss. Six novel and two reported pathogenic variants in OPA1 (GenBank
Accession No. NM_130837.2) were identified including four nonsynonymous variants
(c.2400T > G, c.1468T > C, c.1567A > G and c.1466T > C), two splicing variants
(c.2984-1_2986delGAGA and c.2983 + 5G > A), one small deletion
(c.2960_2968delGCGTTCAAC), and one small insertion (c.3009_3010insA). RNA
analysis revealed the splicing variant c.2984-1_2986delGAGA caused small deletion
of mRNA (r.2983_2988del). CONCLUSIONS: ADOA patients presented variable clinical
manifestations. Novel OPA1 pathogenic variants are the main genetic defect for
Chinese ADOA cases. NGS may be a useful molecular testing tool for atypical ADOA.
PMID- 29952690
TI - Epididymal ultrastructural changes associated with chronic cholestasis after bile
duct ligation in adult rats.
AB - Testicular atrophy and testesterone insufficiency have been commonly reported
associated with chronic liver diseases. Though testosterone dependent, the
epididymal changes induced by liver disease have never been studied before. Thus,
this study aimed to assess the ultrastructural events in the epididymis of rats
with chronic obstructive jaundice. Chronic cholestasis induced many epididymal
structural alterations manifested by the reduced tubular diameters, thickening of
the tubular basement membrane, and regression of the principal cells. This was
accompanied with reduction of principal cell organelles, cytoplasmic
vacuolations, nuclear alterations, and stereovilli loss. The results establish
that chronic cholestasis causes epididymal structural changes due to androgen
deficiency.
PMID- 29952691
TI - Low dose ionizing irradiation suppresses cellular senescence in normal human
fibroblasts.
AB - PURPOSE: Exposure to high dose ionizing radiation leads to premature cell
senescence and suppression of cell proliferation. In contrast, low dose and low
dose-rate gamma-irradiation can lead to stimulation of cell proliferation. We
aimed to examine whether the low dose radiation-induced proliferation of normal
human fibroblasts can lead to a progressive depletion of proliferation potential
and to an early onset of senescence. MATERIALS AND METHODS: Normal human
embryonic lung fibroblasts (HELF-104) at passage 22-24 were gamma-irradiated with
doses of 0 (sham-irradiation), 10, 30, 50, 90, 120, 150, 200, and 500 mGy as well
as 1 and 2 Gy. After irradiation, the fraction of cells positively stained for
senescence-associated beta-galactosidase activity was measured weekly until the
cell culture completely ceased to proliferate. RESULTS: We show that single
irradiation of HELF-104 cells with 30 and 50 mGy resulted in deceleration of
senescence. The suppression of senescence was observed during almost the entire
length of the study up to a complete arrest of cell growth. CONCLUSIONS: Our
data, together with the previously published observation of delayed stimulation
of proliferation in HELF-104 cells exposed to 30 mGy, suggest that low dose gamma
irradiation can increase the overall proliferative potential of normal human
fibroblasts.
PMID- 29952692
TI - The impact of progressive pelvic floor muscle exercise and manual therapy in a
patient postpartum who met the criteria for sacroiliac joint pain based on
Laslett's cluster of provocation signs.
AB - Sacroiliac joint (SIJ) pain has been identified as a primary or contributing
source of pain in patients with low back pain. The Laslett cluster of SIJ pain
provocation tests has the strongest evidence for noninvasive clinical testing.
The purpose of this report was to describe the impact of physical therapy
treatments for a patient postpartum with SIJ pain who satisfied the Laslett
cluster. Specifically, the goal was to assess the impact of progressive pelvic
floor muscle exercise and manual therapy. The Modified Oswestry Low Back Pain
Disability Questionnaire (MODI) was the primary outcome measure used in this
case. In addition, the Numeric Pain Rating Scale (NRPS) and Global Rating of
Change (GROC) were used as secondary outcome measures. In this case report, the
patient responded to the combined interventions with decreases in MODI, NRPS and
GROC. Further research is warranted to develop stronger evidence to identify
specific interventions for the treatment of SIJ pain.
PMID- 29952693
TI - Photobiomodulation Therapy is More Effective than Cryotherapy for Skeletal Muscle
Recovery: A Critically Appraised Topic.
AB - Clinical Scenario: Cryotherapy is one of the most commonly used modalities for
post-exercise muscle recovery despite inconsistencies in the literature
validating its effectiveness. With the need to find a more effective modality,
photobiomodulation therapy (PBMT) has gained popularity because of recent
research demonstrating its ability to accelerate the muscle recovery process.
Focused Clinical Question: Is PBMT more effective than cryotherapy at reducing
recovery time and decreasing delayed onset muscle soreness (DOMS) after strenuous
exercise? Summary of Key Findings: Three moderate- to high quality double
blinded, randomized placebo-controlled trials and two low- to moderate quality
translational studies performed on rats were included in this CAT. All 5 studies
supported the use of PBMT over cryotherapy as a treatment for post-exercise
muscle recovery following exercise. PBMT was superior in reducing creatine
kinase, inflammation markers, and blood lactate compared to cryotherapy following
strenuous/high intensity aerobic or strength muscular exercise. PBMT was also
shown to improve post-exercise muscle performance and function more than
cryotherapy. Clinical Bottom Line: There is moderate evidence to suggest the use
of PBMT over cryotherapy post-exercise to enhance muscle recovery in trained and
untrained athletes. Shorter recovery times and increased muscle performance can
be seen 24 to 96 hours following PBMT application. Strength of Recommendation:
Based on consistent findings from all 5 studies, there is grade B evidence to
support the use of PBMT over cryotherapy for more effective post-exercise
recovery of skeletal muscle performance.
PMID- 29952694
TI - Balance-confidence is associated with community participation, perceived physical
mobility, and performance-based function among individuals with a unilateral
amputation.
AB - OBJECTIVE: To explore relationships between balance-confidence and: 1) community
participation; 2) self-perceived mobility; and 3) performance-based physical
function among individuals with a lower-limb amputation using a prosthetic.
DESIGN: Retrospective, cross-sectional study. SETTING: Outpatient,
multidisciplinary amputee clinic. PARTICIPANTS: Patients (n = 45) using a
prosthesis, aged >= 18 years, with a unilateral transfemoral or transtibial
amputation of >=1 year, were included. METHODS: Participants completed the
following self-report measures: Activities-Specific Balance Confidence Scale
(ABC); Community Integration Questionnaire (CIQ); Locomotor Capabilities Index
(LCI); and two performance-based measures (i.e. Timed Up and Go and 6 Minute Walk
Test). Linear regression modeling was used to explore relationships between
balance-confidence (i.e. ABC) and self-report (i.e. CIQ and LCI) and performance
based measures (p <= 0.0125). RESULTS: After controlling for potential covariates
(i.e. age, sex, and body mass index), balance-confidence explained 47.4% of the
variance in CIQ (p = 0.000), 53.0% of the variance in LCI (p = 0.000), 20.3% of
the variance in Timed Up and Go (p = 0.001), and 18.2% of the variance in 6
Minute Walk Test (p = 0.001). CONCLUSION: Lower balance-confidence is associated
with less community participation, lower self-perceived mobility, and poorer
performance among patients with a unilateral lower-limb amputation.
PMID- 29952695
TI - A Randomized Controlled Trial Investigating the Feasibility and Adherence to an
Aerobic Training Program in Healthy Individuals.
AB - CONTEXT: Concussion management is moving from passive rest strategies to active
interventions, including aerobic exercise therapy. Little information is
available regarding the feasibility and adherence of these programs. OBJECTIVES:
To determine whether an aerobic exercise training program, intended for
rehabilitation in persons with concussion, is feasible. Healthy non-concussed
subjects were studied in this Phase I trial. DESIGN: Phase 1 parallel-group
randomized controlled trial in a sample of healthy (non-concussed),
recreationally active university students. SETTING: Laboratory. PATIENTS: 40
healthy, university students. METHODS: Participants were equally randomized into
acute concussion therapy intervention (ACTIVE) training or non-training groups.
All participants completed maximal cardiopulmonary exercise tests (CPETs) on a
stationary cycle ergometer at two test sessions approximately 14 days apart.
During this 2-week study period, ACTIVE training participants completed six 30
minute cycling sessions, progressing from 60-80% of the participant's
individualized maximal oxygen consumption (VO2max). A subset of participants
(NACTIVE=12, Nnon-training=11) wore physical activity monitors throughout the 2
week study period. MAIN OUTCOMES MEASURES: Study protocol and randomization
effectiveness, exercise safety and adherence, and progressive intensity of the
ACTIVE training procedures. RESULTS: No adverse events occurred during any
exercise sessions. Twelve ACTIVE training participants (60%) completed all
training sessions and every participant completed at least four sessions. Heart
rate increased throughout the training period (p<0.001), but symptom changes and
training adherence remained stable despite the progressively increasing workload.
ACTIVE training participants completed approximately 30 additional minutes of
physical activity on training sessions days, although not statistically
significant (p=0.20). CONCLUSIONS: University aged students were adherent to the
ACTIVE training protocol. Future research should investigate the safety and
feasibility of aerobic training programs in acutely concussed individuals to
determine their appropriateness as a clinical rehabilitation strategy.
PMID- 29952696
TI - Real-time Biofeedback is More Effective Than Sham Feedback for Modifying High
Risk Biomechanics.
AB - CONTEXT: Existing anterior cruciate ligament (ACL) injury prevention programs
have failed to reverse the high rate of ACL injuries in adolescent female
athletes. OBJECTIVE: This investigation attempts to overcome factors that limit
efficacy with existing injury prevention programs through the use of a novel,
objective, and real-time interactive visual feedback system designed to reduce
the biomechanical risk factors associated with ACL injuries. DESIGN: Crossover
study. SETTING: Medical center laboratory. PARTICIPANTS: Twenty female
participants (age = 19.7 +/- 1.34 y; height = 1.74 +/- 0.09 m; weight = 72.16 +/-
12.45 kg). METHODS: Participants performed sets of 10 bodyweight squats in each
of eight training blocks (i.e., four real-time and four control blocks) and three
testing blocks for a total of 110 squats. Feedback conditions were blocked and
counterbalanced with half of participants randomly assigned to receive the real
time feedback block first and half receiving the control (sham) feedback first.
RESULTS: Heat map analysis revealed that during interaction with the real-time
feedback, squat performance measured in terms of key biomechanical parameters was
improved compared to when participants squatted with the sham stimulus.
CONCLUSION: This study demonstrates that the interactive feedback system guided
participants to significantly improve movement biomechanics during performance of
a body weight squat, which is a fundamental exercise for a longer-term ACL injury
risk reduction intervention. A longer training and testing period is necessary to
investigate the efficacy of this feedback approach to effect long-term
adaptations in the biomechanical risk profile of athletes.
PMID- 29952697
TI - Efficacy of ReBound Diathermy as a Thermal Heating Agent: A Critically Appraised
Topic.
AB - : Clinical Scenario: ReBound (ReGear Life Sciences, Inc, Pittsburgh, PA) is a
portable shortwave diathermy unit (SWD) used to heat tissues using the same
principle as induction drum SWD. It is unclear if ReBound can vigorously (4
degrees C) heat intramuscular tissue as efficiently as other thermal agents.
CLINICAL QUESTION: In adults (P), is ReBound diathermy (I) compared to other
thermal agents (C) effective at increasing intramuscular tissue temperature by 4
degrees C (O)? Summary of Key Findings: Three studies were included for review,
all randomized crossover studies. All studies agreed ReBound does not achieve
vigorous (4 degrees C) heating effects during a 30-minute treatment to the
triceps surae muscle (depth=1 and 3-cm). Studies agreed the heat generated via
ReBound dissipates slower than (p<.001) or similarly to PSWD at 3 cm and faster
than moist hot packs (MHP, p<.001) at 1 cm. One study found intramuscular tissue
temperatures increased more with ReBound (3.69 degrees C+/-1.50 degrees C) than
MHP (2.82 degrees C+/-.90 degrees C) at superficial depths (1-cm, d=.70). Two
studies compared ReBound to MegaPulse II PSWD at a 3-cm depth. One found the
MegaPulse II increased intramuscular tissue temperature by 4.32 degrees C+/-1.79
degrees C compared to the ReBound's 2.31 degrees C+/-.87 degrees C increase
(d=1.43). The final study reported the MegaPulse II increased triceps surae
muscle temperature by 3.47 degrees C+/-.92 degrees C versus ReBound at 3.08
degrees C+/-1.19 degrees C (d=.37). The combined results are an increase of
3.81+/-1.38 degrees C for the MegaPulse II and 2.77+/-1.12 degrees C for ReBound
(d=.83). Clinical Bottom Line: Results strongly indicate ReBound should not be
used for vigorous (4 degrees C) heating effects in the triceps surae muscle at 1
and 3-cm. Clinicians can use ReBound when traveling or instead of MHP for
moderate (2-3 degrees C) heating effects at deep and superficial levels (1 and 3
cm) for large treatment areas with subcutaneous fat thickness <15 mm. Strength of
Recommendation: Consistent level B findings indicate ReBound does not achieve
vigorous heating effects (4 degrees C).
PMID- 29952698
TI - Hop Stabilization Training Improves Neuromuscular Control in Collegiate
Basketball Players with Chronic Ankle Instability: A Randomized Controlled Trial.
AB - CONTEXT: Neuromuscular control deficit has been reported in people with chronic
ankle instability (CAI) and hopping exercises have been recommended as a
functional training tool to prevent lower limb injury, but its effects on lower
extremity neuromuscular control in those with CAI are unclear. OBJECTIVE: To
investigate the effect of hop stabilization training on neuromuscular control and
self-reported function in collegiate basketball players with CAI. STUDY DESIGN: A
randomized controlled trial. SETTING: Research Laboratory. Patients (or Other
Participants): Twenty-eight college basketball players with CAI were randomly
assigned to the experimental hop stabilization group (age 22.78+/- 3.09 years,
weight 82.59+/- 9.51 kg, height 187.96+/- 7.93 cm) or the control group (age
22.57+/- 2.76 years, weight 78.35+/- 7.02 kg, height 185.69+/- 7.28 cm).
INTERVENTION: Participants in the experimental group performed supervised hop
stabilization exercises 3 times per week for 6 weeks. The control group received
no intervention. MAIN OUTCOME MEASURES: Preparatory and reactive muscle
activation levels and muscle onset time were assessed from eight lower extremity
muscles during a jump landing task before and after the 6-week training program.
RESULTS: Significant improvements in preparatory muscle activation, reactive
muscle activation, and muscle onset time were noted across the lower extremity in
the experimental group relative to the control group (p <0.05). Self-reported
function also improved in the experimental group relative to the control group (p
<0.05). CONCLUSIONS: These findings demonstrate that 6-weeks of hop stabilization
training is effective in improving neuromuscular control and self-reported
function in collegiate basketball players with CAI. Hop stabilization exercises
can be incorporated into rehabilitation program for CAI.
PMID- 29952699
TI - Influence of Foam Rolling Velocity on Knee Range of Motion and Tissue Stiffness:
A Randomized, Controlled Crossover Trial.
AB - CONTEXT: Foam Rolling (FR) increases joint range of motion (RoM), but the optimal
training parameters are unknown. OBJECTIVE: To investigate the effect of FR
velocity on RoM and tissue stiffness. DESIGN: Randomized, controlled crossover
trial. SETTING: University. PARTICIPANTS: Seventeen healthy, physically active
adults (25+/-2 years, 10 females). INTERVENTIONS: 1) 4x45s high-velocity FR of
the anterior thigh (FAST-FR), 2) 4x45s slow-velocity FR of the anterior thigh
(SLOW-FR), 3) inactive control (CON) Outcome measures: Maximal knee flexion RoM
(ultrasonic movement analysis) and anterior thigh tissue stiffness (semi
electronic tissue compliance meter), assessed assessed pre, immediately post
(T0), as well as five (T5), and ten (T10) minutes post-intervention. Statistical
analysis included Friedman tests with adjusted post-hoc comparisons (Wilcoxon
tests). RESULTS: According to omnibus testing, RoM remained unchanged in all
three conditions and at all time points (p>.05), while differences were found for
tissue stiffness (p<.05): Post-hoc tests revealed significant decreases following
FAST-FR (T5:-17%, T10:-24%; p<.05) and SLOW-FR (T10: -15%; p<.05). The observed
stiffness changes were significant in comparison to CON (p<.01), but no
difference was found between the two FR conditions (p>.05). CONCLUSIONS: FR of
the anterior thigh decreases myofascial stiffness regardless of velocity. The
lack of effects on RoM contrasts findings of recent literature and warrants
further investigation.
PMID- 29952700
TI - Theta Phase Synchronization between the Human Hippocampus and Prefrontal Cortex
Increases during Encoding of Unexpected Information: A Case Study.
AB - Events that violate predictions are thought to not only modulate activity within
the hippocampus and PFC but also enhance communication between the two regions.
Scalp and intracranial EEG studies have shown that oscillations in the theta
frequency band are enhanced during processing of contextually unexpected
information. Some theories suggest that the hippocampus and PFC interact during
processing of unexpected events, and it is possible that theta oscillations may
mediate these interactions. Here, we had the rare opportunity to conduct
simultaneous electrophysiological recordings from the human hippocampus and PFC
from two patients undergoing presurgical evaluation for pharmacoresistant
epilepsy. Recordings were conducted during a task that involved encoding of
contextually expected and unexpected visual stimuli. Across both patients,
hippocampal-prefrontal theta phase synchronization was significantly higher
during encoding of contextually unexpected study items, relative to contextually
expected study items. Furthermore, the hippocampal-prefrontal theta phase
synchronization was larger for contextually unexpected items that were later
remembered compared with later forgotten items. Moreover, we did not find
increased theta synchronization between the PFC and rhinal cortex, suggesting
that the observed effects were specific to prefrontal-hippocampal interactions.
Our findings are consistent with the idea that theta oscillations orchestrate
communication between the hippocampus and PFC in support of enhanced encoding of
contextually deviant information.
PMID- 29952701
TI - Higher Psoriasis Skin Clearance Is Associated with Lower Annual Indirect Costs in
the United States: A Post Hoc Analysis from the CLEAR Study.
AB - BACKGROUND: Psoriasis is associated with a high economic burden to society. New
psoriasis systemic treatments offer the potential for improved skin clearance.
Whether a higher degree of clearing translates into economic benefit through
decreased work impairment has not been fully determined. OBJECTIVE: To assess
whether more complete clearing of psoriasis is associated with a reduction in
disease-related indirect costs. METHODS: Pooled data from employed patients
included in the CLEAR study, a phase 3b study comparing the efficacy and safety
of secukinumab (337 subjects) versus ustekinumab (339 subjects), were classified
into 4 levels of skin clearance improvement at weeks 16 and 52: Psoriasis Area
and Severity Index (PASI) improvement from baseline of < 50% (PASI < 50), 50%-74%
(PASI 50-74), 75%-89% (PASI 75-89), and >= 90% (PASI >= 90). Patients completed
the Work Productivity and Activity Impairment questionnaire for psoriasis (WPAI
PSO), which assessed absenteeism, presenteeism, and a composite overall work
impairment over the previous 7 days at weeks 16 and 52. U.S. Department of Labor
data were used to calculate annual indirect costs due to work productivity loss.
RESULTS: In the CLEAR study, 452 (67%) were employed at baseline and included in
this analysis. At week 16, mean overall work impairment significantly decreased
with higher PASI improvements: 22.8% for PASI < 50, compared with 13.3% for PASI
50-74 (P = 0.001); 6.4% for PASI 75-89 (P < 0.001); and 4.9% for PASI >= 90 (P <
0.001), with the majority of work impairment related to presenteeism. Calculated
mean work hours lost by overall work impairment decreased with higher PASI
improvements: 8.2 hours lost/week (429 hours/year) for patients with PASI 50; 4.6
hours lost/week (251 hours/year) for PASI 50-74; 2.3 hours lost/week (121
hours/year) for PASI 75-89; and 1.8 hours lost/week (93 hours/year) for PASI >=
90. Associated mean annual indirect costs due to work productivity loss per
worker decreased with higher PASI improvements: $10,318 for PASI < 50, $6,042 for
PASI 50-74, $2,901 for PASI 75-89, and $2,233 for PASI >= 90. Similar results
were observed at week 52. Mean overall work impairment decreased with higher PASI
improvements, ranging from 26.3% for PASI < 50 to 6.9% for PASI >= 90. A decrease
in overall work hours lost (ranging from 9.5 hours lost/week [495 hours/year] for
PASI < 50 to 2.5 hours/week [130 hours/year] for PASI >= 90), as well as
associated annual indirect costs due to work productivity loss (ranging from
$11,906 for PASI < 50 to $3,125 for PASI >= 90), were also shown with higher PASI
improvements at week 52. CONCLUSIONS: Among working patients with moderate to
severe psoriasis, higher PASI improvements were associated with lower work
productivity loss and reduced annual indirect costs. By improving and sustaining
skin clearance, psoriasis treatments may contribute to increased work
productivity and decreased societal economic burden. DISCLOSURES: Funding for
this study was provided by Novartis Pharmaceuticals. Zhao and Herrera are
employed by Novartis. Gilloteau is employed by Novartis Pharma AG. McBride,
Graham, and Miles are employed by RTI Health Solutions, which provides consulting
and other research services to pharmaceutical, device, governmental, and
nongovernmental organizations and received funding from Novartis for manuscript
development, analysis development, and general consultation. Feldman reports
grants and personal fees from Novartis, Abbvie, Janssen, Lilly, and Celgene,
along with personal fees from Amgen and Valeant.
PMID- 29952702
TI - The Authors Respond.
AB - DISCLOSURES: Funding for the Carlson et al. study was provided in part by the
Institute for Clinical and Economic Review. Ollendorf, Synnott, Chapman, and
Pearson disclosed grants from Blue Shield of California Foundation, California
Health Care Foundation, Laura and John Arnold Foundation, Aetna, AHIP, Anthem,
Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health
Care, OmedaRx, United Healthcare, Kaiser Permanente, Premera, AstraZeneca,
Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical
Council, Takeda, Pfizer, Novartis, Lilly, Spark Therapeutics, Sanofi, Prime
Therapeutics, and Health Care Service Corporation. Carlson disclosed grants from
the Institute for Clinical and Economic Review and personal fees from Seattle
Genetics, Genentech, and Pfizer. Russo, Guzauskas, Liu, and Brouwer have nothing
to disclose.
PMID- 29952703
TI - The Effect of FDA Drug Safety Communications on Patterns of Tiotropium
Dispensing: A U.S. Health Plan Claims Database Study.
AB - BACKGROUND: The FDA issued 2 main drug safety communications (DSCs) on the
cardiovascular safety of tiotropium in March 2008 (warning of a potential
increased stroke risk) and January 2010 (informing of an absence of a significant
increased stroke risk or cardiovascular events based on findings from a large
trial). OBJECTIVE: To describe the effect of the FDA DSCs on medication
dispensing of tiotropium in a large U.S. claims database. METHODS: Initiation of
tiotropium products among patients with chronic obstructive pulmonary disease
(COPD) aged 40 years and older was determined monthly from 2006-2012 using
medication dispensing from the IMS Lifelink Health Plan Claims Database.
Similarly, monthly initiation of products containing long-acting beta-agonists
(LABAs) was calculated to explore product switching. The effect of the 2008 and
2010 FDA DSCs was measured using interrupted time-series analysis. Subgroups of
patients with greater cardiovascular risk were also examined. RESULTS: A
decreasing trend in initiation of tiotropium-containing products was present
before the initial 2008 DSC. The decline in tiotropium initiation continued until
January 2010, accompanied by an increased initiation of LABA-containing products
in patients with COPD. In the presence of the existing decreasing trend, the
initial DSC was followed by an immediate 2.8% (P = 0.02) further reduction in
tiotropium initiation. Tiotropium initiation increased 2.5% (P = 0.03)
immediately after the 2010 DSC, reducing the overall decline in rate and
stabilizing (flattening) the trend. No significant changes in dispensing level or
trend were observed among COPD patients with cardiovascular comorbidity.
CONCLUSIONS: Cardiovascular safety concerns may have affected tiotropium
initiation as indicated by the decrease in tiotropium dispensing shown
immediately following the initial DSC. The effect was alleviated as concerns
lessened following the most recent DSC. DISCLOSURES: This research did not
receive any specific grant from funding agencies in the public, commercial, or
not-for-profit sectors. The authors are employed by the FDA and have no conflict
of interest relevant to the content of this study. The views expressed herein do
not necessarily represent the views of the FDA.
PMID- 29952704
TI - Treatment Patterns Among Patients with Psoriatic Arthritis Treated with a
Biologic in the United States: Descriptive Analyses from an Administrative Claims
Database.
AB - BACKGROUND: In patients with psoriatic arthritis (PsA), limited data exist
regarding patterns of biologic therapy use. OBJECTIVE: To examine treatment
patterns and therapy modifications in U.S. patients with PsA receiving a tumor
necrosis factor inhibitor (TNFi) or an anti-interleukin (IL)-12/23 inhibitor.
METHODS: Adults with PsA who newly initiated a biologic therapy (index biologic)
between January 1, 2013, and January 31, 2015, were included from the Optum
Research Database. Biologic therapies comprised those that were approved by the
FDA for the treatment of PsA at the time of the study initiation (adalimumab,
certolizumab pegol, etanercept, golimumab, infliximab, or ustekinumab). Outcomes
included adherence, persistence, and discontinuation of the index biologic;
initiation of adjunctive medications (nonbiologics, including those commonly used
for pain and/or inflammation); and dose escalation of the index biologic during
the 12-month follow-up period. RESULTS: Of the 1,235 patients included, 52.5%
were female, and mean (SD) age was 50.3 (12.1) years. The mean (SD) duration of
persistence with a newly initiated index biologic (etanercept [48.1%], adalimumab
[24.0%], infliximab [10.4%], golimumab [8.3%], ustekinumab [7.2%], or
certolizumab pegol [2.0%]) was 246 (128) days; 44.5% of patients persisted with
the index biologic for >= 12 months. During the 12-month follow-up period, 22.9%
of patients switched to a different biologic, 26.8% discontinued without
switching or restarting, and 5.8% discontinued and restarted the index biologic.
Of the 1,010 patients who persisted with the index biologic for > 90 days, 45.6%
received >= 1 adjunctive medication during the period from 90 days after the
index date to the end of persistence or 12 months. The most commonly initiated
adjunctive medications were corticosteroids (22.0%), opioids (17.1%), and
nonsteroidal anti-inflammatory drugs (12.9%). Overall, 9.6% of patients had a
dose escalation of the index biologic in the immediate 12-month post-index
period. CONCLUSIONS: This real-world study of treatment patterns for PsA, which
used a large U.S. claims database, demonstrated that the majority of patients
with PsA discontinued their index biologic (TNFi or anti-IL-12/23 inhibitor)
before 12 months. Nearly half of patients initiated an adjunctive medication,
many of which were pain and conventional anti-inflammatory medications.
DISCLOSURES: This study was sponsored by Novartis Pharmaceuticals. Optum was
commissioned by Novartis to conduct this study, but employment was not contingent
on results of the study. Walsh is a paid consultant for Novartis. Adejoro was an
employee of Optum at the time of the study and writing of the manuscript. Chastek
is an employee of Optum. Palmer and Hur are employees of Novartis. Results of
this study were presented as an abstract and poster at the Academy of Managed
Care Pharmacy Nexus 2017; October 16-19, 2017; Dallas, TX; and the EULAR 2017
Annual European Congress of Rheumatology; June 14-17, 2017; Madrid, Spain.
PMID- 29952705
TI - Reframing the Value of Treatments for Relapsed/Refractory Multiple Myeloma.
AB - DISCLOSURES: Ailawadhi reports research support from Pharmacyclics and consulting
relationships with Takeda, Amgen, and Celgene. Jakubowiak reports consulting and
advisory board relationships with AbbVie, Amgen, BMS, Celgene, Karyopharm,
SkylineDX, and Takeda. Panjabi, Campioni, and Majer are employees of and
stockholders in Amgen.
PMID- 29952706
TI - The Potential Effect of the 21st Century Cures Act on Drug Development.
AB - : Enacted in December 2016, the 21st Century Cures Act is a pivotal piece of
legislation that will influence the FDA drug and device approval process for the
foreseeable future. Although this legislation received overwhelming support by
members of Congress for much needed budgetary increases for the FDA and other
national health organizations, there is much controversy over certain provisions
that potentially diminish the robustness of the evidence base required for drug
and medical device approvals. This article discusses the key provisions from
"Title III - Development" under "Division A - 21st Century Cures" related to drug
development and, specifically, explores those aspects that address patient
focused drug development, use of surrogate endpoints in clinical trials,
modernization of trial design, and use of real-world evidence for decision making
and health care economic information. In addition, specific legislation on
regulatory changes is discussed pertaining to antimicrobial stewardship.
Essentially, summarized interpretations are presented here of the provisions
covering the aforementioned topics, along with insights into potential intended
and unintended consequences for U.S. health care payers, health care providers,
government entities, and product manufacturers. DISCLOSURES: No outside funding
supported this writing. Goble is completing fellowship training sponsored by
Novartis Pharmaceuticals.
PMID- 29952707
TI - Intravitreal Aflibercept Versus Ranibizumab for Wet Age-Related Macular
Degeneration: A Cost-Effectiveness Analysis.
AB - BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision
loss in the United States. The most severe vision loss occurs in patients with
neovascular AMD, known as wet AMD (wAMD). The most commonly used antivascular
endothelial growth factor (VEGF) therapies approved by the FDA to treat patients
with wAMD are ranibizumab, 0.5 mg administered by intravitreal injection once a
month (approximately every 28 days), and intravitreal aflibercept injection
(IAI), 2 mg every 4 weeks (monthly) for the first 12 weeks (3 months), followed
by IAI 2 mg once every 8 weeks (2 months). Given the similar efficacy and safety
profiles between IAI and ranibizumab, their associated costs and comparative cost
effectiveness are key factors in determining which one represents a more rational
investment of scarce health care resources to help address the increasing cost of
prescription drugs in the United States, a source of concern for patients,
prescribers, payers, and policymakers. OBJECTIVE: To assess the cost
effectiveness of intravitreal aflibercept injection 2 mg every 8 weeks after 3
initial monthly doses (IAI 2q8) versus ranibizumab 0.5 mg monthly (Rq4) and pro
re nata (PRN) in the treatment of patients with wAMD from a U.S. payer
perspective. METHODS: A Markov cohort model was developed to estimate the
lifetime quality-adjusted life-years (QALYs) and costs of treating patients with
wAMD with IAI 2q8, Rq4, and ranibizumab PRN. The model considered changes in best
corrected visual acuity in the affected and fellow eyes over time, and the effect
of blindness on mortality. Efficacy for IAI 2q8 and Rq4 was from VIEW 1 and VIEW
2 studies and from the Comparison of AMD Treatments Trials for ranibizumab PRN.
Utilities and costs (in 2016 U.S. dollars) were from published literature. Health
outcomes and costs were discounted at an annual rate of 3%. RESULTS: Over a
lifetime, IAI 2q8 provided equal health benefits with Rq4 (5.44 QALYs) at a lower
total cost ($33,745 vs. $48,031) as a result of fewer injections. IAI 2q8 yielded
slightly greater QALYs versus ranibizumab PRN (5.44 vs. 5.40) at a slightly
higher cost ($33,745 vs. $33,652), with an incremental cost per QALY gained of
$2,583. Results were sensitive to variations in drug acquisition costs and number
of injections of both drugs and the baseline age of the cohort. CONCLUSIONS: IAI
2q8 can be cost saving and cost-effective compared with Rq4 and ranibizumab PRN
for the treatment of wAMD in the United States. DISCLOSURES: This study was
funded by Regeneron Pharmaceuticals, the manufacturer of aflibercept. Hernandez,
Lanitis, Cele, and Toro-Diaz are employed by Evidera, which received funding from
Regeneron Pharmaceuticals to conduct this study. Gibson and Kuznik are employed
by and own stock in Regeneron Pharmaceuticals.
PMID- 29952708
TI - Effectiveness of Ledipasvir/Sofosbuvir and Predictors of Treatment Failure in
Members with Hepatitis C Genotype 1 Infection: A Retrospective Cohort Study in a
Medicaid Population.
AB - BACKGROUND: The primary goal of therapy for patients with chronic hepatitis C
virus (HCV) infection is eradication of HCV ribonucleic acid, which is predicted
by achievement of sustained virologic response at 12 weeks (SVR12).
Ledipasvir/sofosbuvir was approved by the FDA in 2014 and 2015 as a once-daily
regimen for the treatment of HCV genotype 1 and HCV genotypes 4, 5, and 6,
respectively. Although its efficacy has been demonstrated in randomized
controlled trials, there is an unmet need for real-world effectiveness data and
studies that assess the association of rates of SVR12 with specific clinical and
demographic factors in the Medicaid population. OBJECTIVES: To (a) evaluate the
effectiveness of HCV genotype 1 treatment with ledipasvir/sofosbuvir as measured
by the rate of SVR12 overall and within the subgroups of 8-, 12-, and 24-week
regimens and (b) identify predictors of treatment failure in the Massachusetts
Medicaid (MassHealth) population. METHODS: This retrospective cohort study
evaluated the rate of SVR12 among 796 MassHealth Primary Care Clinician and fee
for-service plan members who completed treatment with at least one 8-, 12-, or 24
week treatment with ledipasvir/sofosbuvir for HCV genotype 1 infection between
October 10, 2014, and November 1, 2016. The following variables were evaluated to
identify predictors of treatment failure: sex, history of treatment failure,
cirrhosis, substance use disorder, human immunodeficiency virus coinfection, and
concomitant use of interacting medications. The proportion of members who
achieved SVR12 was calculated for the entire study population and stratified by
treatment regimen. Chi-square tests were used to compare the proportion of
members who achieved SVR12, stratified by clinical and demographic variables.
RESULTS: SVR12 was achieved in 95% (756/796) of members. High proportions of
members who received 8 weeks of treatment or 12 weeks of treatment without
concomitant ribavirin achieved SVR12 (96.0% [285/297] and 95.7% [382/399],
respectively). A slightly lower proportion of members who received 12 weeks of
treatment with concomitant ribavirin or 24 weeks of treatment achieved SVR12
(89.9% [62/69] and 87.1% [27/31], respectively). The proportion of members who
achieved SVR12 with each treatment regimen was consistent when stratified by
clinical and demographic variables. None of the included variables were found to
be associated with statistically significant differences in odds of treatment
failure. CONCLUSIONS: In the Medicaid population of 1 state, treatment of HCV
genotype 1 infection with ledipasvir/sofosbuvir was associated with a high rate
of SVR12. The outcomes of treatment of HCV genotype 1 infection with
ledipasvir/sofosbuvir in the Medicaid population are comparable with outcomes
observed in other patient populations. DISCLOSURES: No outside funding supported
this study. The authors have no financial disclosures. A poster of this
manuscript was presented at the Academy of Managed Care Pharmacy 2017 Annual
Meeting, March 27-30, 2017, in Denver, Colorado.
PMID- 29952709
TI - Hemophilia Burden of Disease: A Systematic Review of the Cost-Utility Literature
for Hemophilia.
AB - BACKGROUND: Prophylaxis with clotting factor replacement products is recommended
by the Medical and Scientific Advisory Council of the National Hemophilia
Foundation as the optimal therapy for the prevention of bleeding episodes in
individuals with severe hemophilia A or B (< 1 IU per dL endogenous factor VIII
or factor IX activity, respectively). Prophylaxis is associated with an improved
health-related quality of life and has been shown to be cost-effective compared
with on-demand therapy. However, the overall cost of treatment remains high,
particularly among patients with a greater propensity to bleed. The overall value
of hemophilia treatments and their associated benefits, measured in quality
adjusted life-years (QALYs), and dollar costs compared with other interventions
can be evaluated through the use of cost-utility analyses (CUAs). Previous CUA
studies in hemophilia have focused primarily on patients with more severe forms
of hemophilia and on prophylaxis compared with on-demand treatment. However, to
our knowledge, no studies to date have utilized QALYs as a standardized outcome
measure to systematically evaluate the relative cost-effectiveness of current
hemophilia treatment options. OBJECTIVE: To systematically review the CUA
literature of hemophilia treatments and demonstrate the challenges in producing
cost-utility evidence compared with other rare diseases. METHODS: We conducted a
systematic literature review using the Tufts Medical Center Cost-Effectiveness
Analysis Registry and the National Health Service Economic Evaluation Database
for English-language CUAs published from 2000 through 2015 with the search terms
hemophilia, haemophilia, factor VIII, or factor IX. Two trained reviewers
independently reviewed every study to extract relevant data. Incremental cost
effectiveness ratios were converted to 2014 U.S. dollars using exchange rates for
currency conversion and the Consumer Price Index to adjust for inflation.
RESULTS: Our search yielded 52 studies, 11 of which met our inclusion criteria.
The cost-effectiveness of hemophilia treatments varied widely based on variations
in the study designs, including differences in time horizon, discount rates, and
medical interventions. CONCLUSIONS: We found the cost-effectiveness of hemophilia
treatments to be broadly comparable to that of other orphan drugs. Improved
standardization of future CUA studies will be important for further evaluation of
the cost-effectiveness of hemophilia treatments. DISCLOSURES: This research was
funded by Biogen, which provided an unrestricted research grant to the Center for
the Evaluation of Value and Risk in Health at Tufts Medical Center. Biogen and
Sobi reviewed and provided feedback on the manuscript. The authors had full
editorial control of the manuscript and provided final approval of all content.
The authors report no conflict of interest regarding the material discussed in
this article. Neumann and Chambers are employed at the Center for the Evaluation
of Value and Risk in Health at Tufts Medical Center. Thorat was an employee of
Center for Evaluation Value and Risk in Health, Tufts Medical Center when the
analyses were carried out. Chambers has participated on advisory boards for
Sanofi and Astellas Pharma.
PMID- 29952710
TI - Evaluating the Effect of Treatment Persistence on the Economic Burden of Moderate
to Severe Psoriasis and/or Psoriatic Arthritis Patients in the U.S. Department of
Defense Population.
AB - BACKGROUND: Psoriasis is a chronic, hyper-proliferative dermatological condition
associated with joint symptoms known as psoriatic arthritis (PsA). In a 2013
review, the total economic burden of PsA was estimated at $51.7-$63.2 billion.
The economic burden of moderate to severe psoriasis patients has reduced
significantly with the advent of biologics, but there remains a dearth of real
world evidence of the impact of treatment persistence on the economic burden of
moderate to severe psoriasis and/or PsA patients. OBJECTIVE: To evaluate the
overall and psoriasis and/or PsA-related health care utilization and costs among
patients who were persistent versus those nonpersistent on index biologic among
the moderate to severe psoriasis and/or PsA population. METHODS: Adult patients
with >= 2 claims with diagnosis of psoriasis and/or PsA during the period of
November 2010-October 2015 were identified from the U.S. Department of Defense
database; the first diagnosis date during November 2011-October 2014 was defined
as the index date. As of the index date, patients were considered to have
moderate to severe psoriasis or PsA if they had >= 1 nontopical systemic therapy
or phototherapy during the 1-year pre- or 1-month post-index date. Persistence to
index therapy, defined as the first biologic used (etanercept, adalimumab,
ustekinumab, infliximab) on or within 30 days post-index date, was determined
based on the biologic dosing schedule and a 90-day gap. Generalized linear models
were used to compare the health care utilization and costs between persistent and
nonpersistent patients during the 1-year post-index period. RESULTS: A total of
2,945 moderate to severe psoriasis and/or PsA patients were identified. Of those,
1,899 (64.5%) were persistent and 1,046 (35.5%) were nonpersistent. Compared with
nonpersistent patients, persistent patients were older (49.2 vs. 45.5 years; P <
0.001) and more likely to be male (52% vs. 45%; P < 0.001). More persistent
patients were diagnosed with dyslipidemia (40% vs. 35%; P = 0.002), had lower
antidepressant use (23.4% vs. 27.4%; P < 0.001), and had lower anxiolytic use
(30% vs. 37%; P < 0.001) compared with nonpersistent patients. After adjusting
for demographic and clinical characteristics, nonpersistent patients had higher
total medical costs ($12,457 vs. $8,964; P < 0.001) compared with persistent
patients, and ambulatory visits (23.9 vs. 21.4; P = 0.007) were a major
contributor. Approximately 40% of the total overall medical costs were attributed
to psoriasis and PsA. Although persistent patients incurred higher pharmacy costs
($10,684 vs. $7,849; P < 0.001) due to higher biologic use and the potentially
high per-unit cost of biologics, their psoriasis- and/or PsA-related medical
costs were significantly lower than those of nonpersistent patients ($3,395 vs.
$5,041; P < 0.001). Total overall costs combining medical and pharmacy costs were
similar between the cohorts ($22,678 vs. $21,477; P = 0.122). CONCLUSIONS:
Moderate to severe psoriasis and/or PsA patients who were persistent on index
biologic treatment had higher pharmacy utilization and costs, albeit with lower
medical costs and similar total costs, compared with nonpersistent patients.
DISCLOSURES: This study was funded by Janssen Scientific Affairs. Lee is a paid
employee of Janssen Scientific Affairs. Xie, Wang, Vaidya, and Baser are paid
employees of STATinMED Research, which is a paid consultant to Janssen Scientific
Affairs. This study was presented as an abstract at the Academy of Managed Care
Pharmacy 2017 Annual Meeting, March 27-30, 2017, in Denver, CO.
PMID- 29952711
TI - Sustained Virologic Response and Costs Associated with Direct-Acting Antivirals
for Chronic Hepatitis C Infection in Oklahoma Medicaid.
AB - BACKGROUND: Outcomes involving newer direct-acting antiviral (DAA) hepatitis C
virus (HCV) regimens have not been studied extensively among the Medicaid
population. OBJECTIVE: To assess clinical (treatment failure) and economic
outcomes for chronic HCV-infected Oklahoma Medicaid members following treatment
with DAAs and to measure associations with patient, treatment, and clinical
characteristics. METHODS: This cross-sectional study used Oklahoma Medicaid
pharmacy and medical claims data for adult members who used a newer DAA agent and
had reported a successful or failed sustained virological response rate 12 weeks
after therapy completion (SVR12) from January 1, 2014, to June 30, 2016.
Multivariable logistic and gamma regressions assessed predictors of SVR12 failure
and costs controlling for member demographics (i.e., age, sex, race, rural
residence); type of DAA and adherence; clinical characteristics (e.g., comorbid
conditions, advanced liver disease); and the implementation of changes to a prior
authorization program. RESULTS: Of 934 Medicaid members eligible for treatment
with DAAs between January 1, 2014, and June 30, 2016, 906 received DAA treatment,
40.6% (368/906) had reported SVR12 outcomes, and 59.4% (n = 538) did not have a
reported SVR recorded. Of those with reported SVR12 outcomes, patients were 53.1
+/- 9.7 years of age, 51.1% were male, 8.4% had SVR12 failure, and each member
had mean costs of $140,283 +/- $52,779. Multivariable analyses indicated higher
odds of SVR12 failure was independently associated with cirrhosis (OR
[decompensated] = 6.69 and OR [compensated] = 3.52, P < 0.001), while males had
higher odds of failure than females (OR = 3.34, P < 0.010). No significant
difference in SVR12 failure was noted, according to DAA type or a medication
adherence threshold of > 95%. Ledipasvir/sofosbuvir was independently associated
with lower costs (exp[b] = 0.81; P < 0.001) compared with sofosbuvir, while
higher costs were associated with decompensated cirrhosis (exp[b] = 1.22; P <
0.001) and treatment failure (exp[b] = 1.18, P < 0.010). In an analysis including
members without reported SVR12 outcomes, decompensated and compensated cirrhosis
had lower odds (P < 0.001) of no reported SVR12 from ambulatory clinic settings.
CONCLUSIONS: Almost 60% of Medicaid members receiving DAA treatment did not have
a final reported SVR12 outcome. Among those with viral load measurements,
treatment success was high and both decompensated and compensated cirrhosis were
independently associated with significantly higher odds of treatment failure.
Addressing a loss to follow-up among HCV patients and curtailing the development
of cirrhosis to improve treatment success may warrant interventions that improve
access to care and remove barriers that impede treatment initiation and
completion. DISCLOSURES: No outside funding supported this study. Pham, Keast,
Holderread, Nesser, and Skrepnek disclose either employment by the Oklahoma
Health Care Authority or contractual work for this employer. Pham discloses
fellowship funding from Purdue Pharma unrelated to this study. Keast and Skrepnek
disclose research grant funding from Gilead Sciences and Abbvie. Holderread also
reports grant funding from Gilead Sciences and fees from PRIME Education.
Thompson, Farmer, and Rathbun have nothing to disclose.
PMID- 29952712
TI - Real-World Characteristics and Treatment Patterns in Patients with Urticaria
Initiating Omalizumab in the United States.
AB - BACKGROUND: Omalizumab is indicated for the management of chronic idiopathic
urticaria (CIU) in patients aged 12 years or older with persistent hives that are
not adequately controlled by H1 antihistamines. While its safety and efficacy in
CIU patients have been evaluated in multiple clinical trials, real-world use of
omalizaumab in CIU has not been well characterized. OBJECTIVE: To assess
demographics, clinical characteristics, and treatment patterns of CIU patients
who initiated omalizumab to better understand the usage of this agent in CIU
management in the real world. METHODS: This retrospective cohort study used
medical and pharmacy claims data in the United States from the HealthCore
Integrated Database to identify patients with CIU newly treated with omalizumab
(>= 4 omalizumab claims within 6 months of the initial claim) between March 21,
2014, and October 31, 2015 (study intake period). The index date was defined as
the date of the first claim for omalizumab during the study intake period.
Demographic and clinical characteristics were described for patients treated with
omalizumab, as were treatment patterns associated with omalizumab and concomitant
medications associated with CIU treatment. Descriptive and inferential statistics
were reported. The Kaplan-Meier method was used to examine omalizumab treatment
patterns. RESULTS: This study included 298 omalizumab-treated patients (mean [SD]
age of 43.5 [13.64] years; 70.8% female); approximately 84% were seen by an
allergist/immunologist. All patients had >= 12 months of continuous enrolment and
a subset of 138 patients had >= 18 months of follow-up. For patients with >= 12
months of post-index follow-up, 12.1% (n = 36), 28.5% (n = 85), and 32.9% (n =
98) discontinued omalizumab within the 6-month, 12-month, and the entire post
index periods (mean 530 days), respectively; the mean number of days patients
were continuously treated with omalizumab was 443.1 (95% CI = 425.0-461.3); the
probabilities of continuous treatment (95% CI) were 0.879 (0.836-0.911), 0.711
(0.656-0.759), and 0.647 (0.585-0.703) for the 6-, 12-, and 18-month post-index
periods, respectively. For the 98 patients who discontinued omalizumab during the
entire post-index period, 28.6% restarted omalizumab after the first
discontinuation within the post-index period (mean time from first
discontinuation to first restart=329 days). Use of medications such as oral
corticosteroids, montelukast, cyclosporine, and prescription H1 and H2
antihistamines decreased during the 1- to 6-month and 7- to 12-month post-index
periods compared with those within the 6-month pre-index period. CONCLUSIONS: In
this cohort of CIU patients who were newly prescribed omalizumab, the majority
were treated by allergists/immunologists as expected, and approximately 60% of
patients continued on therapy beyond 18 months. Concomitant medication use
decreased after omalizumab initiation. These data on the real-world use of
omalizumab for CIU may help to better inform decision-making processes for health
care payers by quantifying omalizumab and concomitant medication treatment
patterns over a longer time frame relative to previous studies. DISCLOSURES: This
study was sponsored by Novartis Pharmaceuticals, which provided funding support
for the conduct of the study. Kavati, Ortiz, and Paknis are employees of Novartis
Pharmaceuticals. Ke, Wertz, Huang, Wang, Willey, and Stephenson are employees of
HealthCore, an independent research organization that received funding from
Novartis Pharmaceuticals for the conduct of this study. Beck is an employee of
the University of Rochester Medical Center, who was under contract with Novartis
Pharmaceuticals to provide consulting services to this study, and reports grants
from Genentech, outside the currently submitted work. Bernstein is affiliated
with Bernstein Clinical Research Center, which was under contract with Novartis
Pharmaceuticals to provide consulting services to this study, and reports
receiving grants and personal fees from Novartis Pharmaceuticals, grants and
personal fees from Genentech outside of the submitted work, and is an author on
the Joint Task Force for Practice Parameters for Urticaria and the GALEN
international guidelines for urticaria under preparation. Selected study data
were presented in a poster at the International Society for Pharmacoeconomics and
Outcomes Research (ISPOR) 22nd Annual International Meeting on May 20-24, 2017,
in Boston, MA. A poster based on this dataset was presented at the 2017 American
College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting on
October 26-30, 2017, in Boston, MA.
PMID- 29952713
TI - AMCP Partnership Forum: Managing Care in the Wave of Precision Medicine.
AB - Precision medicine, the customization of health care to an individual's genetic
profile while accounting for biomarkers and lifestyle, has increasingly been
adopted by health care stakeholders to guide the development of treatment
options, improve treatment decision making, provide more patient-centered care,
and better inform coverage and reimbursement decisions. Despite these benefits,
key challenges prevent its broader use and adoption. On December 7-8, 2017, the
Academy of Managed Care Pharmacy convened a group of stakeholders to discuss
these challenges and provide recommendations to facilitate broader adoption and
use of precision medicine across health care settings. These stakeholders
represented the pharmaceutical industry, clinicians, patient advocacy, private
payers, device manufacturers, health analytics, information technology, academia,
and government agencies. Throughout the 2-day forum, participants discussed
evidence requirements for precision medicine, including consistent ways to
measure the utility and validity of precision medicine tests and therapies,
limitations of traditional clinical trial designs, and limitations of value
assessment framework methods. They also highlighted the challenges with evidence
collection and data silos in precision medicine. Interoperability within and
across health systems is hindering clinical advancements. Current medical coding
systems also cannot account for the heterogeneity of many diseases, preventing
health systems from having a complete understanding of their patient population
to inform resource allocation. Challenges faced by payers, such as evidence
limitations, to inform coverage and reimbursement decisions in precision
medicine, as well as legal and regulatory barriers that inhibit more widespread
data sharing, were also identified. While a broad range of perspectives was
shared throughout the forum, participants reached consensus across 2 overarching
areas. First, there is a greater need for common definitions, thresholds, and
standards to guide evidence generation in precision medicine. Second, current
information silos are preventing the sharing of valuable data. Collaboration
among stakeholders is needed to support better information sharing, awareness,
and education of precision medicine for patients. The recommendations brought
forward by this diverse group of experts provide a set of solutions to spur
widespread use and application of precision medicine. Taken together, successful
adoption and use of precision medicine will require input and collaboration from
all sectors of health care, especially patients. DISCLOSURES This AMCP
Partnership Forum and the development of the proceedings document were supported
by Amgen, Foundation Medicine, Genentech, Gilead, MedImpact, National
Pharmaceutical Council, Precision for Value, Sanofi, Takeda, and Xcenda.
PMID- 29952715
TI - Treatment of amblyopia: Part 3 Apparatus, exercise equipment and games
(continued).
PMID- 29952714
TI - Serious Adverse Drug Events Reported to the FDA: Analysis of the FDA Adverse
Event Reporting System 2006-2014 Database.
AB - BACKGROUND: Data on adverse drug events (ADEs) observed at the population level
provide important evidence regarding the safety of a pharmaceutical product in
real-world settings. Recent patterns in serious and fatal ADE reporting have not
been documented. OBJECTIVE: To assess recent patterns in serious and fatal ADE
reports in the United States. METHODS: We conducted a retrospective analysis of
the publicly available 2006-2014 FDA Adverse Event Reporting System database. Non
U.S. reports, reports from clinical trials, and reports with missing outcome data
were excluded. The annual numbers of ADEs with reported outcome of death,
disability, and other serious outcomes were determined. Types (direct,
manufacturer expedited, or manufacturer periodic) and sources (consumer, health
professional, or other) of these serious ADE reports were also identified. The
distribution of serious ADE reports by patient age groups (< 18, 18-44, 45-64,
and >= 65 years) was determined. Drugs listed as primary suspects in serious ADEs
(death, disability, and other serious outcomes) were identified and ranked.
Descriptive statistics were used to characterize the patterns in serious or fatal
ADE reporting. RESULTS: From 2006 to 2014, the number of serious ADEs reported to
the FDA increased 2-fold. A total of 902,323 serious outcomes were reported over
the 9-year study period: 244,408 deaths, 72,141 disabilities, and 585,774 other
serious outcomes. The relative percentage of reports of deaths was highest during
2012 (32.4%). The percentage of reports of disability was highest during 2006
(12.1%). Overall, the "other serious outcomes" category accounted for almost 65%
of serious ADEs reports. Expedited reports from drug manufacturers were most
common (about 72%) of the serious ADEs with available data on report type. Health
professionals (47.3%) were the most common source of report followed by consumers
(36.1%) and other sources (16.6%). A disproportionately high number of reported
ADEs was among patients aged 45-64 years (40%) and >= 65 years (32.6%).
Antineoplastic drugs were more frequently reported with deaths. Three
antidepressant drugs were among the top 10 drugs reported with disability. During
2006-2014, there were 38 drugs with more than 1,000 reports of serious ADEs in a
given year: 2 drugs currently withdrawn from the market (rofecoxib and
parecoxib), 10 drugs with an FDA risk evaluation and mitigation strategies (REMS)
program, 13 biologic or specialty drugs, and 14 others. CONCLUSIONS: An overall
increase in the trend of the number of serious ADE reports was observed from 2006
to 2014. Drugs with a REMS program and biologic and specialty drugs were involved
in a significant number of reported serious ADEs. Data on reporting patterns can
guide surveillance and pharmacoepidemiological studies to understand the public
health burden of serious ADEs. DISCLOSURES: No outside funding supported this
study. Hansen has received consulting fees from and has provided expert testimony
for Daichii Sankyo and Takeda. The other authors have nothing to disclose.
PMID- 29952716
TI - Inositol polyphosphate-4-phosphatase type II plays critical roles in the
modulation of cadherin-mediated adhesion dynamics of pancreatic ductal
adenocarcinomas.
AB - The inositol polyphosphate-4-phosphatase type II (INPP4B) has been mostly
proposed to act as a tumor suppressor whose expression is frequently dysregulated
in numerous human cancers. To date, little is unveiled about whether and how
INPP4B will exert its tumor suppressive function on the turnover of cadherin
based cell-cell adhesion system in pancreatic ductal adenocarcinomas (PDACs) in
vitro. Here we provide the evidence that INPP4B manipulates cadherin switch in
certain PDAC cell lines through a phosphorylated AKT-inactivation manner. The
knockdown of INPP4B in AsPC-1 results in a more invasive phenotype, and
overexpression of it in PANC-1 leads to partial reversion of mesenchymal status
and impediment of in vitro invasion but not migration. More importantly, E
cadherin (Ecad) is enriched in the early and sorting endosomes containing INPP4B
by which its recycling rather than degradation is enabled. Immunohistochemical
analysis of 39 operatively resected PDAC specimens reveals it is poorly
differentiated, non-cohesive ones in which the INPP4B and Ecad are partially or
completely compromised in expression. We therefore identify INPP4B as an tumor
suppressor in PDAC which attenuates AKT activation and participates in
preservation of Ecad in endocytic pool and cellular membrane.
PMID- 29952717
TI - Political Beliefs, Region of Residence, and Openness to Firearm Means Safety
Measures to Prevent Suicide.
AB - Firearms account for approximately half of all suicides in the United States and
are highly lethal, widely available, and popular; thus, are an ideal candidate
for targeted means safety interventions. However, despite their value as a
suicide prevention tool, firearm means safety strategies are not widely utilized,
possibly due to factors which impede openness to their use. This study examines
the relationship between region, political beliefs, and openness to firearm means
safety in a sample of 300 American firearm owners. Overall, firearm owners were
more willing to engage in means safety for others than for themselves and to
store firearms safely than temporarily remove them from the home. Social policy
views and region were significantly associated with openness to firearm means
safety measures, however, economic policy views were not. This study provides
further context for the development and implementation of efficacious means
safety measures capable of overcoming potential barriers to their use.
PMID- 29952718
TI - The impact of trait mindfulness on relational outcomes in novice yoga
practitioners participating in an academic yoga course.
AB - OBJECTIVE: This study examined the role of dispositional mindfulness in impacting
the relational benefits of yoga in novice practitioners in an undergraduate
academic yoga course. PARTICIPANTS: 21 college students enrolled in a yoga course
throughout a 15-week academic semester (January-April 2016). METHODS:
Participants attended lab assessments at the beginning and end of the semester
and were asked to complete eight consecutive Internet-based daily surveys across
six separate bursts, yielding 48 data points for each participant. RESULTS:
Multivariate time-series analyses revealed within-person subgroup differences
such that in general, those in the high trait mindfulness group gleaned benefits
from yoga practice with respect to relational outcomes. CONCLUSIONS: This study
demonstrated trait mindfulness impacts relational outcomes in novice yoga
practitioners, suggesting those low in trait mindfulness may not garner immediate
relational benefits from yoga and could benefit from additional strategies to
bolster against any negative influences of initiating yoga practice.
PMID- 29952719
TI - Lysis characteristics and mechanism of excess sludge degraded by ozone and
ultrasonic treatment.
AB - As a byproduct of activated sludge process, excess sludge has become one of the
current problems in the field of environmental protection for its yield huge,high
moisture content and easy to pollution. In this study, the joint technology
combining ozone with ultrasonic was applied in treatment of excess sludge by
strong ozone oxidation and prominent ultrasonic cavitation. The effect on lysis
excess sludge cells was explored comprehensively. The lysis mechanism of excess
sludge cells degraded by ozone + ultrasonic was revealed by analysis of three
dimensional spectral fluorometer, optical microscope and scanning electron
microscopy (SEM). The results showed that the MLSS was 22.92% lower than the
untreated sludge, the SCOD and [Formula: see text] -N content in the supernatant
of the sludge was 1792 and 105.77 mg/L, which was 96.49% and 17.67% higher than
the untreated. The supernatant of treated excess sludge contained macromolecular
organic matters composed of proteins, polysaccharides, humic acids, and fulvic
acids, etc. The whole process of lysis cells of excess sludge degraded by ozone +
ultrasonic could be inferred that the microbial particles of excess sludge were
exposed after EPS destructed, and then the cell walls of these exposed microbial
particles were broken so that a great number of intracellular materials were
released. Furthermore, these intracellular material composed of macromolecular
organic matters were degraded into small molecule organic matters, H2O, CO2, etc.
Finally, the excess sludge was treated gradually by ozone + ultrasonic.
PMID- 29952720
TI - Promoting evidence-based practice - perceived knowledge, behaviours and attitudes
of Polish nurses: a cross-sectional validation study.
AB - PURPOSE: Evidence-based practice (EBP) is recognized by the healthcare community
as the gold standard for the provision of safe and compassionate healthcare. The
aim was to describe nurses' knowledge, behaviours and attitudes regarding EBP.
MATERIALS AND METHODS: A cross-sectional approach was conducted during specialty
state examinations in Poland in 2014 in a sample of 548 nurses. The self
completed reliable and valid evidence-based practice profile questionnaire
(Australia) was used. Statistical analysis included Cronbach's alpha coefficient,
analysis of variance, the Guttman split-half method and calculations in
Statistica version 12. RESULTS: Although the participants' beliefs about the
benefits of EBP were high, their knowledge was relatively low. Statistically
significant correlations were found between barriers and practice, knowledge and
attitudes in relation to the level of nurses' education (p < 0.001 to p < 0.05).
Total Cronbach's alpha coefficient was 0.970. CONCLUSIONS: Study findings
highlight the importance of further supplementation of knowledge about EBP. The
difficulties in using EBP in clinical practice are objective and require changes
in the Polish system of nursing care. Additionally, life-long updating knowledge
in the area of EBP by participation in various forms of postgraduate education
can produce improvements in the knowledge, behaviours and attitudes of nurses in
creating a positive EBP profile.
PMID- 29952721
TI - Environmental risk assessment of chronic arsenic in drinking water and prevalence
of type-2 diabetes mellitus in Pakistan.
AB - Chronic arsenic (As) unprotection in drinking water can lead to Type 2 Diabetes
Mellitus (T2DM). The purpose of this study was to investigate the association
between chronic As in drinking water and the prevalence of T2DM. A study was
conducted in targeted urban areas of Peshawar city of KPK, Pakistan, where
drinking water is heavily contaminated with chronic arsenic. Participants
protected to arsenic were selected from Kohat city of KPK, Pakistan (where people
consumed water that is free from As contamination) and treated as the control
group. People with arsenic-related skin lesions were defined as participants
unprotected to arsenic. T2DM was diagnosed using a glucometer following the
fasting blood glucose >=6.0 mmol L-1 from the WHO guideline. The common odds
ratio for T2DM among participants unprotected to arsenic was <4. The Mantel
Haenszel weighted prevalence ratio with 95% of confidence interval for
confounding factors were (age <4 m femininity <4 and body mass index >4). The
results revealed that designated association were important. The findings
suggested that unprotected chronic arsenic in drinking water may be a risk factor
of T2DM.
PMID- 29952722
TI - DDR1 and DDR2 in skin.
AB - DDR1 and DDR2 are expressed in skin but their expression differs according to the
skin compartment, epidermis, dermis, hypodermis and to the embryonic origin of
the cells. In skin, it seems that during physiological processes such as wound
healing or pathological processes such as tumorigenesis or systemic sclerosis
development only one of the DDR is dysregulated. Furthermore, the altered DDR in
pathological process is not necessarily the DDR implicated in basal homeostasis.
Indeed, in epidermis, while DDR1 is the main DDR involved in melanocyte
homeostasis, DDR2 seems to be the main DDR implicated in melanoma. On the
contrary, in dermis, while DDR2 is necessary for normal wound healing,
dysregulation of DDR1 is associated with abnormal wound healing leading to
keloid. In conclusion, targeting DDR could be a therapeutic solution, however
side effects have to be managed carefully.
PMID- 29952723
TI - Moving college health research forward: Reconsidering our reliance on statistical
significance testing.
AB - Understanding the unique health needs of college students and establishing best
practices to address them depend, heavily, on the inherent quality and
contribution of the research identifying these needs. College health-focused
publications currently exemplify less than ideal statistical reporting practices.
Specifically, college health practitioners and researchers continue to rely
heavily upon null hypothesis significance testing (NHST) as the sole standard for
effectiveness, validity, and/or replicability of scientific studies, even though
NHST itself was not designed for such purposes. Herein we address the following
questions: (a) What is NHST? (b) What are the inherent limitations of NHST? (c)
What are recommended alternatives to NHST? and (d) How can editorial policies
promote adopting NHST alternatives? Using college health data from the CORE 2011
Alcohol and Drug survey, we provide a heuristic example demonstrating how effect
sizes do not suffer from the same limitations as NHST.
PMID- 29952724
TI - Self-Injurious Behaviors and Adult Attachment: A Review of the Literature.
AB - Self-injurious behaviors (SIB) continue to afflict a significant segment of the
clinical and general population, sometimes with fatal consequences. The
development of SIB seems to share developmental pathways and mechanisms similar
to attachment insecurity. To date, no reviews have explored their relationship. A
search of publication databases PubMed and PsychInfo from 1969 through April 2018
was conducted and 17 papers met inclusion criteria. Of the 17 articles
identified, 13 reported a positive relationship and 1 reported a negative
relationship between attachment insecurity and SIB. Both attachment anxiety and
avoidance seem to play a role in the risk for SIB, possibly through different
mechanisms and likely with different impacts on the choice for either self-harm
or suicide attempts.
PMID- 29952725
TI - The effects of backpack type on lumbo-pelvic coordination during trunk bending
and return tasks.
AB - Backpacks with ergonomic features are recommended to mitigate the risk of
developing low back pain due to carrying a heavy school backpack. A repeated
measure study was conducted on 40 college-age students to investigate the
immediate changes in magnitude and timing aspects of lumbo-pelvic coordination
when carrying an ergonomically modified vs. a normal backpack relative to no
backpack condition during trunk forward bending and backward return tasks. We
found a smaller reduction in the thoracic range of rotation, an increase vs. a
decrease in pelvic range of rotation and a larger reduction in lumbar flexion for
a modified vs. a normal backpack. Furthermore, during the forward bending, a less
in-phase motion for the modified backpack was observed. Our results suggest that
participants have likely experienced larger spinal loads with the modified
backpack; a conclusion that should be investigated in future to determine whether
ergonomic backpacks can reduce the risk of low back pain in children.
Practitioner summary: Research participants performed trunk bending and return
closer to their habitual way under modified versus normal school backpack. From
an equilibrium point of view, therefore, individuals are likely experiencing
larger spinal loads during activities of daily living with a modified backpack.
However, such a conclusion may change when considering stability requirements.
PMID- 29952726
TI - Carcinoma in situ within an area of Barrett esophagus in a dog with
megaesophagus.
AB - A 10-y-old Irish Setter was presented with a history of recurrent episodes of
regurgitation and vomiting, with more recent development of tachypnea.
Megaesophagus had been diagnosed in the dog 2 y prior to this presentation. A
solitary polypoid mass present immediately rostral to the lower esophageal
sphincter was biopsied during percutaneous endoscopic gastrostomy tube placement.
Barrett esophagus was diagnosed based on the observation of a polypoid mass with
intestinal metaplasia that arose from the surrounding esophagus. Histology of the
polypoid mass demonstrated squamous-to-columnar metaplasia, hyperplasia,
dysplasia, and carcinoma in situ.
PMID- 29952728
TI - The risk factors of abusive relationships for nontraditional students.
AB - OBJECTIVE: To examine the effect of nontraditional student status on abusive
relationships, namely emotional, physical, and sexual abuse. PARTICIPANTS: The
2011-2014 American College Health Association National College Health Assessment
(ACHA-NCHA) II data (N = 102,563) were utilized for the analysis. METHODS:
Logistic regression models were employed as the outcome variables were
dichotomous. RESULTS: Non-traditional students compared to traditional ones
indeed had higher odds ratios of having abusive relationships. Nontraditional
students compared to traditional students, however, were more likely to
experience emotional and physical abuse, but not sexual abuse. CONCLUSIONS: The
prevention programs and policies related to abusive relationships need to be
address differently based on the results of this study, which is also essential
for nontraditional students to adjust and succeed in higher education and further
their careers.
PMID- 29952727
TI - Life after loss: Comparing student service member/veteran and civilian mental
health characteristics among individuals exposed to death by suicide.
AB - OBJECTIVE: This study evaluated the mental health characteristics and beliefs of
student service members/veterans (SSM/Vs) who have been exposed to another's
death by suicide. PARTICIPANTS: A total of 39 SSM/Vs exposed to suicide and 32
SSM/Vs not exposed to suicide were sampled from a larger, epidemiological survey.
An age- and gender-matched group of 39 civilian (C) students was drawn from a
larger sample of individuals exposed to suicide. METHODS: Data were collected as
part of an Internet-based, campus needs survey that occurred in Fall 2014.
Participants were asked to complete measures about suicide-related behaviors,
suicide prevention, help-seeking, and demographics. RESULTS: SSM/Vs exposed to
suicide had more positive mental health/suicide prevention beliefs than SSM/Vs
not exposed to suicide. Cs exposed to suicide were not significantly different
from either group. Unique help-seeking patterns were also identified.
CONCLUSIONS: The current study identifies unique characteristics of SSM/Vs
exposed to suicide that may inform prevention programming.
PMID- 29952729
TI - Meningococcal serogroup B outbreak response University of Wisconsin-Madison.
AB - : A meningococcal serogroup B (MenB) outbreak at a large public university
prompted an emergency response to immunize undergraduates. OBJECTIVE: To report
on a successful meningococcal serogroup B (MenB) vaccine clinic response at a
large public university. METHODS: We assembled the team leaders to write this
case report. RESULTS: Activation of the emergency plan and points of dispensing
required cooperation of many units on campus under the leadership of university
health officials with support from Centers for Disease Control and Prevention,
state division of public health and the city-county health department.
Significant efforts to provide consistent messages to students and parents
regarding the outbreak and the availability of the MenB vaccines were made.
Volunteers were recruited to staff the clinics alongside university healthcare
providers. Over 22,000 doses of vaccine were administered. CONCLUSION: We report
our experience and lessons learned which may be helpful to universities in
preventing and responding to disease outbreaks.
PMID- 29952730
TI - Review of Nutrition Screening and Assessment Practices for Long-Term Care
Residents.
AB - The older adult population in Canada is growing, creating a greater demand for
long-term care (LTC) facilities. Seniors living in LTC are more vulnerable to
malnutrition, making it important to implement nutrition screening tools on a
routine basis. The purpose of this study was to explore the practices of
Registered Dietitians (RDs) related to nutritional screening, nutritional
assessment, and follow-ups conducted within LTC facilities. This study also
explored possible barriers hindering the application of these practices. Nine RDs
from two health regions in Southern Saskatchewan completed a phone interview to
address nutrition care practices/policies and barriers in LTC facilities. Results
showed a considerable amount of variability in nutrition care practices for
screening and assessment with lack of time identified as the greatest barrier.
These findings highlight the importance of having consistent policies and a
sufficient amount of RDs available in LTC facilities to provide the expected
level of nutrition care for residents.
PMID- 29952731
TI - Grandiose and vulnerable narcissism: Associations with alcohol use, alcohol
problems and problem recognition.
AB - OBJECTIVE: This study fills a gap in the literature by examining the relationship
between two types of narcissism, vulnerable and grandiose, and five alcohol
related outcomes (ie, alcohol use, alcohol problems, evaluation and expectancies
of problems, and readiness to change). PARTICIPANTS: 345 college students (28%
men, 72% women) from a Midwestern university were recruited from undergraduate
psychology courses from April 2015 to October 2016. METHODS: Participants
completed an online survey with questionnaires measuring the variables of
interest. Multiple regression analyses were used to test the hypotheses. RESULTS:
Grandiose narcissism was a positive predictor of alcohol consumption and a
positive (ie, good) evaluation of alcohol-related problems. Vulnerable narcissism
was a positive predictor of alcohol-related problems, problem recognition (ie,
readiness to change), and problem expectancies. CONCLUSIONS: The results speak to
the effects that different types of narcissism have on alcohol use, alcohol
problems and attitudes towards alcohol problems among young adults.
PMID- 29952732
TI - Ibuprofen biodegradation by hospital, municipal, and distillery activated
sludges.
AB - Ibuprofen (IBU) has been considered as one of emergent pharmaceutical
contaminants in environments due to its occurrences in natural water bodies. Some
reports suggested that the IBU was biodegradable but details about biodegradation
pathways and functional microbial community were still not fully clear. This
study was aimed to assess IBU biodegradation using three different activated
sludges (i.e. H: hospital, M: municipal, and D: distillery) with foci on
surmising degradation pathway based on UPLC/Q-ToF/MS (ultra-performance liquid
chromatography quadrupole time of flight mass spectrometry) analyses and
concluding microbial community according to high-throughput sequencing for
partial 16S rRNA gene. Results showed that some IBU (~5 mg/L) was able to be
degraded only by sludges H and M during 2-5 days incubation under aerobic
conditions. From LC/MS analysis of degradation byproducts, two major ring-opening
precursors were identified in extracted ion chromatogram data. Ring-opening
degradation pathways leading to the formation of low-molecular-weight carboxylic
acids were elucidated. Additionally, the principal coordinate analyses using Fast
UniFrac method for the partial 16S rRNA gene showed the microbial communities in
the three sludges were significantly different but typically with high proportion
of sequences matched gene fragments from Proteobacteria phylum. Some sequences
with first matches with previously reported IBU degraders (i.e. Nocardia sp.,
Sphingomonas sp., and Variovorax sp.) were only found in the sludges H and M
which showed capability for IBU biodegradation. These results demonstrated some
functional microbes in activated sludges from hospital and municipal WWTPs had
potential to break down IBU into smaller molecules.
PMID- 29952733
TI - A pre/post evaluation of fatigue, stress and vigilance amongst commercially
licensed truck drivers performing a prolonged driving task.
AB - PURPOSE: The main purpose of this research study was to evaluate changes in
fatigue, stress and vigilance amongst commercially licensed truck drivers
involved in a prolonged driving task. The secondary purpose was to determine
whether a new ergonomic seat could help reduce both physical and cognitive
fatigue during a prolonged driving task. Two different truck seats were
evaluated: an industrial standard seat and a new truck seat prototype. METHODS:
Twenty male truck drivers were recruited to attend two testing sessions, on two
separate days, with each session randomized for seat design. During each session,
participants performed two 10-min simulated driving tasks. Between simulated
sessions, participants drove a long-haul truck for 90 min. Fatigue and stress
were quantified using a series of questionnaires whereas vigilance was measured
using a standardized computer test. RESULTS: Seat interactions had a significant
effect on fatigue patterns. CONCLUSION: The new ergonomic seat design holds
potential in improving road safety and vehicle accidents due to fatigue-related
accidents.
PMID- 29952734
TI - Differential Perceptions of a Hypothetical Sexual Assault Survivor Based on Race
and Ethnicity: Exploring Victim Responsibility, Trauma, and Need for Social
Support.
AB - OBJECTIVE: Explore the ways in which a sample of college women interpret
racially/ethnically-coded vignettes to understand their perceptions of
responsibility and trauma experienced by a hypothetical female sexual assault
survivor and her need for social support. PARTICIPANTS: Convenience sample of
college women (N = 51) attending a large, predominately white university in the
Southeastern United States recruited between January-March 2013. METHODS:
Participants were randomly assigned 1 of 3 vignettes describing a hypothetical
date rape scenario. Vignette scenarios were identical except for discrete
statements coded to signify either an African American, Latina, or White female
student. Participants responded to open-ended questions that gauged their
interpretations of responsibility, trauma, and social support. RESULTS:
Qualitative analysis of open-ended responses revealed six overarching themes,
including overt victim blaming/shaming, justification of the sexual assault, and
perceived need for social support. CONCLUSIONS: Findings point to the
significance of including race in discussions about and programs that address
sexual assault on college campuses to ensure that all women who experience sexual
violence receive the support that they need.
PMID- 29952735
TI - Designing effective point-of-choice prompts to promote active transportation and
staircase use at a Canadian University.
AB - OBJECTIVE: The purpose of this study was to determine the most suitable health
messages and designs to create point-of-choice prompts for promoting active
transportation and staircase use that would appeal to undergraduate students.
PARTICIPANTS: Undergraduate students (N = 21; 71% women) were recruited during
Fall (2016) and Winter (2017) semesters. METHODS: Focus groups (50-80 minutes
each) were organized to obtain students' feedback on the kind of messages and
poster designs they found motivational. Inductive content analysis was performed
on verbatim transcripts. Descriptive statistics were calculated to summarize
demographic characteristics of participants. RESULTS: The major themes revealed
that participants: preferred simple designs with tailored messages; had diverse
lifestyle-based values associated with physical activity; and participation in
activities were affected by uncontrollable factors (eg, time, built environment,
and weather). CONCLUSIONS: This study provides insights for designing suitable
point-of-choice prompts that are tailored for university students in terms of
future interventions that aim to improve their activity levels.
PMID- 29952736
TI - Building a Health Communication Brand for University of Texas System Tobacco
Control.
AB - Despite declining cigarette smoking rates in the U.S., there is a continued need
for tobacco prevention education campaigns to reach young adults. This report
describes an initiative from the University of Texas System to develop a health
communication effort that would strengthen tobacco control and prevention efforts
at its 14 diverse institutions. The process involved enlisting expertise in
evidence-based health communication, developing a brand and visual identity for
tobacco control that all of the 14 system institutions could agree on, and
providing all schools the tools to use the new brand effectively. This effort
forged new interdisciplinary connections across academic institutions and offers
a model for other systems of higher education interested in pursuing similar
initiatives.
PMID- 29952737
TI - Cannabis Use Disorder and Post-Deployment Suicide Attempts in Iraq/Afghanistan
Era Veterans.
AB - The objective of the present study was to use retrospective data to test the
hypothesis that cannabis dependence would be associated with an increased rate of
post-deployment suicide attempts. Participants included 319 veterans who had
deployed to either Iraq or Afghanistan. Study procedures involved completion of a
structured clinical interview and a battery of self-report questionnaires. As
expected, lifetime cannabis dependence was significantly associated with post
deployment suicide attempts, AOR = 7.963, p = .014, even after controlling for
the effects of pre-deployment suicide attempts, posttraumatic stress disorder,
depression, pain, non-cannabis substance use disorder, and gender. Although
preliminary, our findings provide the first evidence to date that heavy cannabis
use may be a unique risk factor for post-deployment suicide attempts among
veterans.
PMID- 29952738
TI - Differences in university students' motivation between a required and an elective
physical activity education policy.
AB - OBJECTIVE: The aim of this study was to examine differences in students' physical
activity motivation, competence, and weekly exercise metabolic equivalent units
(METs) between universities with different physical activity education (PAE)
policy arrangements (ie, a required PAE vs. an elective PAE). PARTICIPANTS:
Participants (N = 953) were purposefully recruited from two universities with
different PAE policies 1 week before the start of fall term 2015. METHODS:
Participants completed questionnaires assessing their physical activity
motivation, competence, and weekly exercise METs. RESULTS: The results of this
study suggest that having a required PAE policy allows for more students with
lower self-determined forms of motivation (ie, amotivation) to be reached in
comparison to the elective PAE policy. CONCLUSIONS: This finding highlights that
a primary value of having a required PAE policy is its ability to reach less
motivated students.
PMID- 29952739
TI - Self-injury Age of Onset: A Risk Factor for NSSI Severity and Suicidal Behavior.
AB - This study replicates and extends prior work by examining how age of Non Suicidal
Self-Injury (NSSI) onset relates to NSSI severity, suicidal behavior, perceived
recovery from NSSI, and protective factors of life satisfaction, resilience, and
subjective happiness. University students who reported engaging in NSSI within
the past year (n = 644) completed on-line questionnaires assessing NSSI
characteristics, suicidal behavior, and protective factors. Participants who
began self-injuring at or before age 12 reported significantly more lifetime acts
of NSSI, greater method versatility, and medically severe NSSI than those who
began NSSI at older ages (17 years). Those with a typical age of onset (13-16
years) did not differ from the younger age group on method versatility, medical
severity, past year frequency, or perceived recovery but did differ from those
with an older age of onset. The proportion of individuals reporting suicide
attempts significantly increased as the age of onset became younger. No age of
onset group differences were observed on the protective factors. The age at which
one begins NSSI appears to be a risk factor for increasingly severe NSSI and
potential suicidal behavior. Early detection and intervention is important for
reducing the negative consequences of engaging in NSSI.
PMID- 29952740
TI - Human Vaccines & Immunotherapeutics: News.
PMID- 29952741
TI - Letter from the editor.
PMID- 29952742
TI - Impact of individualized education plans on academic success of youth with early
onset schizophrenia.
AB - PURPOSE: Youth with early onset schizophrenia (EOS) are eligible for an
individualized education plan (IEP) in school settings, yet often have declining
academic performance over time. This study examines the impact of IEP and
comorbid conditions on educational outcomes for youth with EOS. METHOD: We used
mixed models and logistic regression to answer the research questions using data
from 129 youth with EOS who participated in a longitudinal study from 1998 to
2006. RESULTS: Not all children had an IEP in all waves. Of those that did,
findings demonstrated that having an IEP did not improve absenteeism or academic
performance. In addition, regardless of whether they had an IEP, rates of
dropping out were equal. CONCLUSIONS: Social workers should consider more
individualized approaches to IEPs for youth with EOS to target the specific
complexities of the disorder as well as its implications for school success.
PMID- 29952743
TI - Corrigendum.
AB - Ong CB, Herdt TH, Fitzgerald SD. Hyperplastic goiter in two adult dairy cows. J
Vet Diagn Invest 2014;26:810-814. (Original doi: 10.1177/1040638714554441). The
use of mineral supplements as a top dressing and trace mineralized salt noted by
the authors was based on non-documented verbal comments and not based on direct
observation. Therefore, the definitive source of the excess iodine measured in
the thyroid gland of the 2 cows examined was not identified. The acknowledgments
for this case report have been revised to reflect appropriate contributors to the
case. We thank Tom Wood and the Histology Section of the Diagnostic Center for
Population and Animal Health (DCPAH) for technical assistance processing the
slides of the cases in this report. We also thank Drs. Tim Lyons, Daron Jones,
and James Averill for their contributions to this case.
PMID- 29952744
TI - Diagnosis of virulent Newcastle disease in southern California, May 2018.
PMID- 29952745
TI - Comprehensive screening of antimicrobials to control phytoplasma diseases using
an in vitro plant-phytoplasma co-culture system.
AB - Phytoplasmas are plant-pathogenic bacteria that infect many important crops and
cause serious economic losses worldwide. However, owing to an inability to
culture phytoplasmas, screening of antimicrobials on media is difficult. The only
antimicrobials being used to control phytoplasmas are tetracycline-class
antibiotics. In this study, we developed an accurate and efficient screening
method to evaluate the effects of antimicrobials using an in vitro plant
phytoplasma co-culture system. We tested 40 antimicrobials, in addition to
tetracycline, and four of these (doxycycline, chloramphenicol, thiamphenicol and
rifampicin) decreased the accumulation of 'Candidatus (Ca.) Phytoplasma asteris'.
The phytoplasma was eliminated from infected plants by the application of both
tetracycline and rifampicin. We also compared nucleotide sequences of rRNAs and
amino acid sequences of proteins targeted by antimicrobials between phytoplasmas
and other bacteria. Since antimicrobial target sequences were conserved among
various phytoplasma species, the antimicrobials that decreased accumulation of
'Ca. P. asteris' may also have been effective against other phytoplasma species.
These approaches will provide new strategies for phytoplasma disease management.
PMID- 29952746
TI - Rhodanobacter hydrolyticus sp. nov., a novel DNA- and tyrosine-hydrolysing
gammaproteobacterium isolated from forest soil.
AB - A bacterial isolate, designated G-5-5T, was isolated from forest soil at Kyonggi
University. Strain G-5-5T was acid-tolerant and alkali-tolerant. Cells were
strictly aerobic, Gram-stain-negative, catalase- and oxidase-positive, non
motile, non-spore-forming, rod-shaped, and yellow-coloured. Strain G-5-5T
hydrolysed DNA and tyrosine; assimilated d-glucose, maltose, N-acetyl-glucosamine
and l-fucose; and tolerated only 0.5 % NaCl (w/v). Phylogenetic analysis based on
its 16S rRNA gene sequence revealed that strain G-5-5T formed a lineage within
the family Rhodanobacteraceae and that it grouped with but was distinct from
various members of the genus Rhodanobacter. The closest member was Rhodanobacter
umsongensis GR24-2T (97.8 % sequence similarity). The sole respiratory quinone
was Q-8. The major polar lipids of strain G-5-5T were phosphatidylethanolamine,
phosphatidyl-N-methylethanolamine, phosphatidylglycerol and
diphosphatidylglycerol. The major cellular fatty acids were summed feature 9 (iso
C17 : 1omega9c and/or C16 : 0 10-methyl), iso-C15 : 0, iso-C17 : 0, iso-C16 : 0
and anteiso-C15 : 0. The DNA G+C content of strain G-5-5T was 64.1 mol%. DNA-DNA
hybridization relatedness between strain G-5-5T and other close members of the
genus Rhodanobacter ranged from 19 % to 45 %. On the basis of the polyphasic
characterization and phylogenetic analyses, strain G-5-5T represents a novel
species of the genus Rhodanobacter, for which the name Rhodanobacter hydrolyticus
sp. nov. is proposed. The type strain is G-5-5T (=KEMB 9005-533T=KACC 19113T=NBRC
112685T).
PMID- 29952748
TI - Resting-state functional connectivity in individuals with bipolar disorder during
clinical remission: a systematic review.
AB - BACKGROUND: Bipolar disorder is chronic and debilitating. Studies investigating
resting-state functional connectivity in individuals with bipolar disorder may
help to inform neurobiological models of illness. METHODS: We conducted a
systematic review with the following goals: to summarize the literature on
resting-state functional connectivity in bipolar disorder during clinical
remission (euthymia) compared with healthy controls; to critically appraise the
literature and research gaps; and to propose directions for future research. We
searched PubMed/Medline, Embase, PsycINFO, CINAHL and grey literature up to April
2017. RESULTS: Twenty-three studies were included. The most consistent finding
was the absence of differences in resting-state functional connectivity of the
default mode network (DMN), frontoparietal network (FPN) and salience network
(SN) between people with bipolar disorder and controls, using independent
component analysis. However, 2 studies in people with bipolar disorder who were
positive for psychosis history reported DMN hypoconnectivity. Studies using seed
based analysis largely reported aberrant resting-state functional connectivity
with the amygdala, ventrolateral prefrontal cortex, cingulate cortex and medial
prefrontal cortex in people with bipolar disorder compared with controls. Few
studies used regional homogeneity or amplitude of low-frequency fluctuations.
LIMITATIONS: We found heterogeneity in the analysis methods used. CONCLUSION:
Stability of the DMN, FPN and SN may reflect a state of remission. Further, DMN
hypoconnectivity may reflect a positive history of psychosis in patients with
bipolar disorder compared with controls, highlighting a potentially different
neural phenotype of psychosis in people with bipolar disorder. Resting-state
functional connectivity changes between the amygdala, prefrontal cortex and
cingulate cortex may reflect a neural correlate of subthreshold symptoms
experienced in bipolar disorder euthymia, the trait-based pathophysiology of
bipolar disorder and/or a compensatory mechanism to maintain a state of euthymia.
PMID- 29952747
TI - Psychoradiological patterns of small-world properties and a systematic review of
connectome studies of patients with 6 major psychiatric disorders.
AB - BACKGROUND: Brain connectome research based on graph theoretical analysis shows
that small-world topological properties play an important role in the structural
and functional alterations observed in patients with psychiatric disorders.
However, the reported global topological alterations in small-world properties
are controversial, are not consistently conceptualized according to agreed-upon
criteria, and are not critically examined for consistent alterations in patients
with each major psychiatric disorder. METHODS: Based on a comprehensive PubMed
search, we systematically reviewed studies using noninvasive neuroimaging data
and graph theoretical approaches for 6 major psychiatric disorders:
schizophrenia, major depressive disorder (MDD), attention-deficit/hyperactivity
disorder (ADHD), bipolar disorder (BD), obsessive-compulsive disorder (OCD) and
posttraumatic stress disorder (PTSD). Here, we describe the main patterns of
altered small-world properties and then systematically review the evidence for
these alterations in the structural and functional connectome in patients with
these disorders. RESULTS: We selected 40 studies of schizophrenia, 33 studies of
MDD, 5 studies of ADHD, 5 studies of BD, 7 studies of OCD and 5 studies of PTSD.
The following 4 patterns of altered small-world properties are defined from the
perspectives of segregation and integration: "regularization," "randomization,"
"stronger small-worldization" and "weaker small-worldization." Although more
differences than similarities are noted in patients with these disorders, a
prominent trend is the structural regularization versus functional randomization
in patients with schizophrenia. LIMITATIONS: Differences in demographic and
clinical characteristics, preprocessing steps and analytical methods can produce
contradictory results, increasing the difficulty of integrating results across
different studies. CONCLUSION: Four psychoradiological patterns of altered small
world properties are proposed. The analysis of altered small-world properties may
provide novel insights into the pathophysiological mechanisms underlying
psychiatric disorders from a connectomic perspective. In future connectome
studies, the global network measures of both segregation and integration should
be calculated to fully evaluate altered small-world properties in patients with a
particular disease.
PMID- 29952751
TI - The performance of 9-11-year-old children using an SSVEP-based BCI for target
selection.
AB - OBJECTIVE: In this paper, we report the performance of 9-11-year-old children
using a steady-state visual evoked potential (SSVEP)-based brain-computer
interface (BCI) and provide control data collected from adults for comparison.
Children in our study achieved a much higher performance (79% accuracy; average
age 9.64 years old) than the only previous investigation of children using an
SSVEP-based BCI (~50% accuracy; average age 9.86 years old). APPROACH:
Experiments were conducted in two phases, a short calibration phase and a longer
experimental phase. An offline analysis of the data collected during the
calibration phase was used to set two parameters for a classifier and to screen
participants who did not achieve a minimum accuracy of 85%. MAIN RESULTS: Eleven
of the 14 children and all 11 of the adults who completed the calibration phase
met the minimum accuracy requirement. During the experimental phase, children
selected targets with a similar accuracy (79% for children versus 78% for
adults), latency (2.1 s for children versus 1.9 s for adults), and bitrate (0.50
bits s-1 for children and 0.56 bits s-1 for adults) as adults. SIGNIFICANCE: This
study shows that children can use an SSVEP-based BCI with higher performance than
previously believed and is the first to report the performance of children using
an SSVEP-based BCI in terms of latency and bitrate. The results of this study
imply that children with severe motor disabilities (such as locked-in syndrome)
may use an SSVEP-based BCI to restore/replace the ability to communicate.
PMID- 29952750
TI - Multi-scale mapping along the auditory hierarchy using high-resolution functional
UltraSound in the awake ferret.
AB - A major challenge in neuroscience is to longitudinally monitor whole brain
activity across multiple spatial scales in the same animal. Functional UltraSound
(fUS) is an emerging technology that offers images of cerebral blood volume over
large brain portions. Here we show for the first time its capability to resolve
the functional organization of sensory systems at multiple scales in awake
animals, both within small structures by precisely mapping and differentiating
sensory responses, and between structures by elucidating the connectivity scheme
of top-down projections. We demonstrate that fUS provides stable (over days), yet
rapid, highly-resolved 3D tonotopic maps in the auditory pathway of awake
ferrets, thus revealing its unprecedented functional resolution (100/300um). This
was performed in four different brain regions, including very small (1-2 mm3
size), deeply situated subcortical (8 mm deep) and previously undescribed
structures in the ferret. Furthermore, we used fUS to map long-distance
projections from frontal cortex, a key source of sensory response modulation, to
auditory cortex.
PMID- 29952749
TI - Pitx2c orchestrates embryonic axis extension via mesendodermal cell migration.
AB - Pitx2c, a homeodomain transcription factor, is classically known for its left
right patterning role. However, an early wave of pitx2 expression occurs at the
onset of gastrulation in several species, indicating a possible earlier role that
remains relatively unexplored. Here we show that in zebrafish, maternal-zygotic
(MZ) pitx2c mutants exhibit a shortened body axis indicative of convergence and
extension (CE) defects. Live imaging reveals that MZpitx2c mutants display less
persistent mesendodermal migration during late stages of gastrulation. Transplant
data indicate that Pitx2c functions cell non-autonomously to regulate this cell
behavior by modulating cell shape and protrusive activity. Using transcriptomic
analyses and candidate gene approaches, we identify transcriptional changes in
components of the chemokine-ECM-integrin dependent mesendodermal migration
network. Together, our results define pathways downstream of Pitx2c that are
required during early embryogenesis and reveal novel functions for Pitx2c as a
regulator of morphogenesis.
PMID- 29952752
TI - Online EEG artifact removal for BCI applications by adaptive spatial filtering.
AB - OBJECTIVE: The performance of brain-computer interfaces (BCIs) based on
electroencephalography (EEG) data strongly depends on the effective attenuation
of artifacts that are mixed in the recordings. To address this problem, we have
developed a novel online EEG artifact removal method for BCI applications, which
combines blind source separation (BSS) and regression (REG) analysis. APPROACH:
The BSS-REG method relies on the availability of a calibration dataset of limited
duration for the initialization of a spatial filter using BSS. Online artifact
removal is implemented by dynamically adjusting the spatial filter in the actual
experiment, based on a linear regression technique. MAIN RESULTS: Our results
showed that the BSS-REG method is capable of attenuating different kinds of
artifacts, including ocular and muscular, while preserving true neural activity.
Thanks to its low computational requirements, BSS-REG can be applied to low
density as well as high-density EEG data. SIGNIFICANCE: We argue that BSS-REG may
enable the development of novel BCI applications requiring high-density
recordings, such as source-based neurofeedback and closed-loop neuromodulation.
PMID- 29952753
TI - Giant magnetoresistance switching in multilayer graphene grown on cobalt.
AB - Magnetic multilayer devices, showing large magnetoresistance (MR) effects, have
revolutionized magnetic sensing and data storage sectors over the last few
decades. Two-dimensional van der Waals layered materials are relatively new
entrants in this area, and these materials can give rise to large MR effects with
diverse physical origins. Here we report observation of giant MR switching (~10
orders of magnitude) in multilayered graphene grown on cobalt (Co) substrates,
which persists even at room temperature. The origin of this effect is linked with
weak interlayer coupling of the graphene stacks, which gives rise to an
'interlayer MR' effect. This effect is found to be robust against some degree of
inhomogeneity in the graphene stack, making it an attractive platform for the
emerging area of flexible magnetic sensorics.
PMID- 29952754
TI - Nitrogen anion-decorated cobalt tungsten disulfides solid solutions on the carbon
nanofibers for water splitting.
AB - A facile method to prepare nitrogen anion-decorated cobalt tungsten disulfides
solid solutions, retaining ultra-thin WS2-like nanosheet structures (The N-Co x
W1-x S2) anchored on carbon nanofibers (CNFs), is developed. The synergistic
effect of the WS2 nanosheets provides a secure framework for stabilizing the
amorphous Co-S clusters, CNFs substrate and nitrogen anion-decoration
significantly enhances the inherent conductivity of the catalyst, resulting in a
significantly promoted hydrogen evolution reaction activity and stable
performance compared to pure Co9S8 nanoparticles or ultra-thin WS2 nanosheets.
The N-Co x W1-x S2 electrode demonstrates the excellent electrocatalytic
performance, with current density of 10 mA cm-2 at a low overpotential of 93 mV
and Tafel slope of 85 mV dec-1, as well as the long-term stability in acid
electrolyte. The present investigation may provide a feasible strategy for
incorporating other heteroatoms into transitional metal disulfides materials to
design catalysts with highly active and stable performance for water splitting.
PMID- 29952755
TI - The extreme light infrastructure-nuclear physics (ELI-NP) facility: new horizons
in physics with 10 PW ultra-intense lasers and 20 MeV brilliant gamma beams.
AB - The European Strategy Forum on Research Infrastructures (ESFRI) has selected in
2006 a proposal based on ultra-intense laser fields with intensities reaching up
to 1022-1023 W cm-2 called 'ELI' for Extreme Light Infrastructure. The
construction of a large-scale laser-centred, distributed pan-European research
infrastructure, involving beyond the state-of-the-art ultra-short and ultra
intense laser technologies, received the approval for funding in 2011-2012. The
three pillars of the ELI facility are being built in Czech Republic, Hungary and
Romania. The Romanian pillar is ELI-Nuclear Physics (ELI-NP). The new facility is
intended to serve a broad national, European and International science community.
Its mission covers scientific research at the frontier of knowledge involving two
domains. The first one is laser-driven experiments related to nuclear physics,
strong-field quantum electrodynamics and associated vacuum effects. The second is
based on a Compton backscattering high-brilliance and intense low-energy gamma
beam (<20 MeV), a marriage of laser and accelerator technology which will allow
us to investigate nuclear structure and reactions as well as nuclear astrophysics
with unprecedented resolution and accuracy. In addition to fundamental themes, a
large number of applications with significant societal impact are being
developed. The ELI-NP research centre will be located in Magurele near Bucharest,
Romania. The project is implemented by 'Horia Hulubei' National Institute for
Physics and Nuclear Engineering (IFIN-HH). The project started in January 2013
and the new facility will be fully operational by the end of 2019. After a short
introduction to multi-PW lasers and multi-MeV brilliant gamma beam scientific and
technical description of the future ELI-NP facility as well as the present status
of its implementation of ELI-NP, will be presented. The science and examples of
societal applications at reach with these electromagnetic probes with much
improved performances provided at this new facility will be discussed with a
special focus on day-one experiments and associated novel instrumentation.
PMID- 29952756
TI - High resolution subsurface imaging using resonance-enhanced detection in 2nd
harmonic KPFM.
AB - Second harmonic Kelvin probe force microscopy is a robust mechanism for
subsurface imaging at the nanoscale. Here we exploit resonance-enhanced detection
as a way to boost the subsurface contrast with higher force sensitivity using
lower bias voltages, in comparison to the traditional off-resonance case. In this
mode, the second harmonic signal of the electrostatic force is acquired at one of
the eigenmode frequencies of the microcantilever. As a result, high resolution
subsurface images are obtained in a variety of nanocomposites. To further
understand the subsurface imaging detection upon electrostatic forces, we use a
finite element model that approximates the geometry of the probe and sample. This
allows the investigation of the contrast mechanism, the depth sensitivity and
lateral resolution depending on tip-sample properties.
PMID- 29952757
TI - Phase locking value revisited: teaching new tricks to an old dog.
AB - OBJECTIVE: Despite the increase in calculation power over the last few decades,
the estimation of brain connectivity is still a tedious task. The high
computational cost of the algorithms escalates with the square of the number of
signals evaluated, usually in the range of thousands. In this work we propose a
re-formulation of a widely used algorithm that allows the estimation of whole
brain connectivity in much smaller times. APPROACH: We start from the original
implementation of phase locking value (PLV) and re-formulated it in a
computationally very efficient way. What is more, this formulation stresses its
strong similarity with coherence, which we used to introduce two new metrics
insensitive to zero lag synchronization: the imaginary part of PLV (iPLV) and its
corrected counterpart (ciPLV). MAIN RESULTS: The new implementation of PLV avoids
some highly CPU-expensive operations and achieves a 100-fold speedup over the
original algorithm. The new derived metrics were highly robust in the presence of
volume conduction. Moreover, ciPLV proved capable of ignoring zero-lag
connectivity, while correctly estimating nonzero-lag connectivity. SIGNIFICANCE:
Our implementation of PLV makes it possible to calculate whole-brain connectivity
in much shorter times. The results of the simulations using ciPLV suggest that
this metric is ideal to measure synchronization in the presence of volume
conduction or source leakage effects.
PMID- 29952758
TI - Data mining investigation of the association between a limb ballistocardiogram
and blood pressure.
AB - OBJECTIVE: To investigate the association between a limb ballistocardiogram (BCG)
and blood pressure (BP) based on data mining. APPROACH: During four BP-perturbing
interventions, the BCG and reference BP were measured from 23 young, healthy
volunteers using a custom-manufactured wristband equipped with a MEMS
accelerometer and a commercial continuous BP measurement device. Both timing and
amplitude features in the wrist BCG waveform were extracted, and significant
features predictive of diastolic (DP) and systolic (SP) BP were selected using
stepwise linear regression analysis. The selected features were further
compressed using principal component analysis to yield a small set of DP and SP
predictors. The association between the predictors thus obtained and BP was
investigated by multivariate linear regression analysis. MAIN RESULTS: The
predictors exhibited a meaningful association with BP. When three most
significant predictors were used for DP and SP, a correlation coefficient of r =
0.75 +/- 0.03 (DP) and r = 0.75 +/- 0.03 (SP), a root-mean-squared error
(RMSE) of 7.4 +/- 0.6 mmHg (DP) and 10.3 +/- 0.8 mmHg (SP), and a mean
absolute error (MAE) of 6.0 +/- 0.5 mmHg (DP) and 8.3 +/- 0.7 mmHg (SP) were
obtained across all interventions (mean +/- SE). The association was consistent
in all the individual interventions (r ? 0.68, RMSE ? 5.7 mmHg, and MAE ?
4.5 mmHg for DP as well as r ? 0.61, RMSE ? 7.9 mmHg, and MAE ? 6.4 mmHg
for SP on the average). The minimum number of requisite predictors for robust yet
practically realistic BP monitoring appeared to be three. The association between
predictors and BP was maintained even under regularized calibration (r = 0.63
+/- 0.05, RMSE = 9.3 +/- 0.8 mmHg, and MAE = 7.6 +/- 0.7 mmHg for DP as
well as r = 0.60 +/- 0.05, RMSE = 14.7 +/- 1.4 mmHg, and MAE = 11.9 +/
1.1 mmHg for SP (mean +/- SE)). The requisite predictors for DP and SP were
distinct from each other. SIGNIFICANCE: The results of this study may provide a
viable basis for ultra-convenient BP monitoring based on a limb BCG alone.
PMID- 29952759
TI - Shoulder physiotherapy exercise recognition: machine learning the inertial
signals from a smartwatch.
AB - OBJECTIVE: Participation in a physical therapy program is considered one of the
greatest predictors of successful conservative management of common shoulder
disorders. However, adherence to these protocols is often poor and typically
worse for unsupervised home exercise programs. Currently, there are limited tools
available for objective measurement of adherence in the home setting. The goal of
this study was to develop and evaluate the potential for performing home shoulder
physiotherapy monitoring using a commercial smartwatch. APPROACH: Twenty healthy
adult subjects with no prior shoulder disorders performed seven exercises from an
evidence-based rotator cuff physiotherapy protocol, while 6-axis inertial sensor
data was collected from the active extremity. Within an activity recognition
chain (ARC) framework, four supervised learning algorithms were trained and
optimized to classify the exercises: k-nearest neighbor (k-NN), random forest
(RF), support vector machine classifier (SVC), and a convolutional recurrent
neural network (CRNN). Algorithm performance was evaluated using 5-fold cross
validation stratified first temporally and then by subject. MAIN RESULTS:
Categorical classification accuracy was above 94% for all algorithms on the
temporally stratified cross validation, with the best performance achieved by the
CRNN algorithm (99.4%). The subject stratified cross validation, which evaluated
classifier performance on unseen subjects, yielded lower accuracies scores again
with CRNN performing best (88.9%). SIGNIFICANCE: This proof of concept study
demonstrates the technical feasibility of a smartwatch device and supervised
machine learning approach to more easily monitor and assess the at-home adherence
of shoulder physiotherapy exercise protocols.
PMID- 29952760
TI - Oxidation-induced negative Poisson's ratio of phosphorene.
AB - Mechanical properties of phosphorene oxides are investigated by using density
functional theory calculations. Intriguingly, as the oxygen coverage approaches
50%, negative Poisson's ratios are found in the in-plane principal directions,
originating from the asymmetric atomic structure upon oxygen adsorption. It is
demonstrated that the structure of phosphorene oxide is largely weakened compared
with that of pristine phosphorene. Our work indicates that certain unconventional
mechanical properties, such as the negative Poisson's ratio, can be achieved by
tuning the atomic structure through simple processes, which offers a new avenue
to design specific properties at the nanoscale.
PMID- 29952761
TI - Synthesis of vertically aligned CaTiO3 nanotubes with simple hydrothermal method
and its photoelectrochemical property.
AB - Perovskite-type oxides have become the hotspots of functional materials due to
their various excellent performances. As a typical material with a perovskite
structure, CaTiO3 (CTO) possesses a similar band gap to TiO2 with less defects
and recombination centers, which makes it a promising alternative material to
TiO2. In particular, the CTO nanotube structure has a large specific surface area
and unique photochemical and electron-transport properties, and these advantages
further expand its application range. In this paper, a highly ordered and
vertically aligned CTO nanotube array was successfully synthesized by a simple
hydrothermal method with TiO2 nanotube (TNT) arrays as the precursor. It was
found that the CTO nanotube had a higher optical absorption ability (3.4 eV),
photovoltage (500 mV) and photocurrent density (0.004 A cm-1) under ultraviolet
irradiation, compared to the TNT (350 mV and 0.0036 A cm-1). At the same time,
the electrochemical impedance spectroscopy, Mott-Schottky and stability tests
indicate that the CTO nanotube might be a promising alternative choice as the
photoelectric material for a TNT.
PMID- 29952762
TI - Expanding our roster.
PMID- 29952763
TI - The biocreative strategy: Part 1 foundations.
PMID- 29952764
TI - Management of partially impacted mandibular molars using temporary anchorage
devices.
PMID- 29952765
TI - Orthodontic space closure vs. implant-borne crowns in patients with congenitally
missing maxillary lateral incisors.
PMID- 29952766
TI - Preprosthetic orthodontics in an adult with multiple anterior edentulous spaces
and loss of vertical dimension.
PMID- 29952767
TI - Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity
important for thrombosis.
AB - Red blood cells (RBCs) influence rheology, and release ADP, ATP, and nitric
oxide, suggesting a role for RBCs in hemostasis and thrombosis. Here, we provide
evidence for a significant contribution of RBCs to thrombus formation. Anemic
mice showed enhanced occlusion times upon injury of the carotid artery. A small
population of RBCs was located to platelet thrombi and enhanced platelet
activation by a direct cell contact via the FasL/FasR (CD95) pathway known to
induce apoptosis. Activation of platelets in the presence of RBCs led to platelet
FasL exposure that activated FasR on RBCs responsible for externalization of
phosphatidylserine (PS) on the RBC membrane. Inhibition or genetic deletion of
either FasL or FasR resulted in reduced PS exposure of RBCs and platelets,
decreased thrombin generation, and reduced thrombus formation in vitro and
protection against arterial thrombosis in vivo. Direct cell contacts between
platelets and RBCs via FasL/FasR were shown after ligation of the inferior vena
cava (IVC) and in surgical specimens of patients after thrombectomy. In a flow
restriction model of the IVC, reduced thrombus formation was observed in FasL-/-
mice. Taken together, our data reveal a significant contribution of RBCs to
thrombosis by the FasL/FasR pathway.
PMID- 29952769
TI - Inspiring Curiosity and Restoring Humility: The Evolution of Competency-Based
Continuing Medical Education.
AB - Dr. David Price and his colleagues, in their article in this issue of Academic
Medicine, summarize the findings from recent studies regarding the association of
Maintenance of Certification and physicians' learning and improvements in care.
Their evaluation demonstrates that physicians often changed their practice
because of these educational interventions. In this Invited Commentary, the
author argues that, although this finding is reassuring, it may be the right
answer to the wrong question. The critical questions the profession faces are
whether physicians have the humility to routinely submit themselves to the
judgment of their peers, whether they will accept responsibility for managing
their professional competence and that of their colleagues, and whether they are
willing to create a process for identifying and remediating underperforming
clinicians.If certifying boards assume responsibility for this system of
accountability, then each would need to set the competency expectations for
physicians in its specialty areas, allow clinicians to self-identify their core
scope of practice, assume responsibility for summative assessment, provide
formative feedback to participants, and link physicians to recommended
professional development activities. Continuing certification must be sensitive
to the burdens it puts on physicians and recognize engagement in a spectrum of
learning activities that are integrated with daily practice, including continuing
medical education. By assuming responsibility for their own continuing competency
and that of their colleagues, physicians can manifest their commitment to their
patients and their profession.
PMID- 29952770
TI - Can Maintenance of Certification Work? Associations of MOC and Improvements in
Physicians' Knowledge and Practice.
AB - PURPOSE: To summarize the findings of studies, conducted by individuals both
internal and external to the American Board of Medical Specialties (ABMS) Member
Boards, of the associations of Maintenance of Certification (MOC) and
improvements in physicians' knowledge and patient care processes or outcomes.
METHOD: The authors conducted a narrative review of studies identified by
searching PubMed and Web of Science for English-language articles from the United
States published between 2000 and May 2017. To be included, articles had to
examine the relationship of MOC to physician knowledge, clinical practice
processes, or patient care outcomes. The initial search yielded 811 articles.
After two rounds of review and excluding those articles that did not fit the
study criteria, 39 articles were included for analysis. RESULTS: The 39 included
studies were conducted by or included diplomates of 12 ABMS Member Boards. Twenty
two studies examined MOC processes that were developed by an ABMS Board; 17
examined interventions that were developed by nonboard entities but accepted for
MOC credit by an ABMS Board. Thirty-eight studies examined a single component of
MOC; 24 studied the improvement in medical practice component. Thirty-seven
studies reported at least one positive outcome. CONCLUSIONS: Most of the studies
included in this review highlighted circumstances in which MOC was associated
with positive impacts on physician knowledge and patient care processes or
outcomes. Future collaborative research is needed to improve the relevance,
helpfulness, and generalizability of continuing certification to different
physicians across specialties and practice settings.
PMID- 29952771
TI - Physical Findings Mimicking Sexual Abuse in a Drowning Patient Who Was Treated in
the Intensive Care Unit: A Report on a Fatal Case.
AB - Specific or nonspecific findings of sexual abuse may be observed upon examination
of a child. Examination of the genital area is extremely important for the
identification of child sexual abuse (CSA). However, medical conditions detected
in the child's genital area may be misinterpreted as signs of CSA. Herein, we
present a case of a child with suspected CSA who was treated in the intensive
care unit. The following incidental findings were obtained upon anal examination:
dilatation, ecchymosis, laceration, and hemorrhage. This report aims to discuss
the anal examination findings that can mimic CSA.
PMID- 29952768
TI - ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity
following radiation.
AB - DNA-damaging chemotherapy and radiation therapy are integrated into the treatment
paradigm of the majority of cancer patients. Recently, immunotherapy that targets
the immunosuppressive interaction between programmed death 1 (PD-1) and its
ligand PD-L1 has been approved for malignancies including non-small cell lung
cancer, melanoma, and head and neck squamous cell carcinoma. ATR is a DNA damage
signaling kinase activated at damaged replication forks, and ATR kinase
inhibitors potentiate the cytotoxicity of DNA-damaging chemotherapies. We show
here that the ATR kinase inhibitor AZD6738 combines with conformal radiation
therapy to attenuate radiation-induced CD8+ T cell exhaustion and potentiate CD8+
T cell activity in mouse models of Kras-mutant cancer. Mechanistically, AZD6738
blocks radiation-induced PD-L1 upregulation on tumor cells and dramatically
decreases the number of tumor-infiltrating Tregs. Remarkably, AZD6738 combines
with conformal radiation therapy to generate immunologic memory in complete
responder mice. Our work raises the possibility that a single pharmacologic agent
may enhance the cytotoxic effects of radiation while concurrently potentiating
radiation-induced antitumor immune responses.
PMID- 29952772
TI - Ginsenoside Rg1 impairs homologous recombination repair by targeting CtBP
interacting protein and sensitizes hepatoblastoma cells to DNA damage.
AB - The ginsenoside Rg1, the primary pharmacologically active ingredient of the
traditional Chinese herb ginseng, is widely used in the clinical treatment of
diseases of the immune and nervous systems. Recent studies have shown that it
also has an antitumor effect. In this study, we explored the effects of Rg1 on
hepatoblastoma (HB) and its underlying mechanisms. We demonstrated that Rg1
significantly inhibited HB cell growth both in vivo and in vitro. Mechanistic
studies revealed that Rg1 impaired homologous recombination and triggered double
strand breaks in HB cells by directly targeting CtBP-interacting protein (CtIP),
a key double-strand break repair factor, which is highly expressed in HB tissues.
Moreover, we also demonstrated that Rg1 sensitized HB cells to DNA-damaging
agents both in vitro and in vivo. In conclusion, our data not only demonstrate
the potential clinical application of Rg1 as a novel chemotherapeutic candidate
but also offer a mechanism-based therapeutic option by which DNA-damaging agents
can be used in combination with Rg1 to target HB.
PMID- 29952773
TI - Pseudoprogression with subsequent complete response and severe thrombocytopenia
to checkpoint inhibitor immunotherapy in a patient with advanced mucosal melanoma
of the sinonasal cavity.
AB - In this case report, we describe a patient with an inoperable mucosal melanoma of
the sinonasal cavity who achieved an ongoing complete response to combined
immunotherapy with ipilimumab and nivolumab after initial pseudoprogression.
Despite massive enlargement of the tumor 9 weeks after treatment initiation, we
decided to continue with checkpoint inhibitor immunotherapy because of lacking
potent therapeutic alternatives and the possibility of pseudoprogression. In the
computed tomography scan 3 months later, the tumor was no longer detectable. To
date, the patient is still in remission. However, she developed severe immune
related thrombocytopenia and neutropenia that are rarely encountered with
checkpoint inhibitor immunotherapy. Thrombocytopenia did not respond to
corticosteroids, but rapidly improved after the administration of single-dose
intravenous immunoglobulin. This exceptional case highlights the effectiveness of
combined immunotherapy with ipilimumab and nivolumab in mucosal melanoma, the
phenomenon of pseudoprogression, as well as the rare event of immune-related
hematological side effects.
PMID- 29952774
TI - Complicated Total Hip and Knee Replacement in Patients with Underlying Skeletal
and Vascular Disorders.
PMID- 29952775
TI - Bilateral Bicondylar Osteochondritis Dissecans in a Child with Spastic Diplegia
and Crouch Gait: A Case Report.
AB - CASE: The cause of osteochondritis dissecans is unknown. Various hypotheses
suggest mechanical, ischemic, and hereditary causes. We describe a 13-year-old
girl with spastic diplegia, a form of cerebral palsy, who had an associated
crouch gait and presented with bilateral osteochondral defects of the medial and
lateral femoral condyles. CONCLUSION: This case highlights the potential role of
repetitive microtrauma, likely due to the poor biomechanical forces in a crouch
gait, and provides support for a mechanical cause of osteochondritis dissecans.
PMID- 29952776
TI - Atypical Mycobacterial Septic Arthritis of the Wrist: A Report of Two Cases.
AB - CASES: Two patients with human immunodeficiency virus (HIV) developed wrist pain
following the initiation of antiretroviral treatment, and were diagnosed with
chronic atypical mycobacterial septic arthritis. Aggressive operative debridement
led to clinical improvement, provided tissue samples for diagnosis, and allowed
for a targeted long-term antibacterial regimen. CONCLUSION: Clinicians should
consider atypical mycobacterial organisms as a cause of joint infection in
patients with HIV. Symptoms may become apparent after patients experience immune
system recovery following antiretroviral treatment.
PMID- 29952777
TI - Exertional Supraspinatus Syndrome: A Report of Two Cases.
AB - CASE: We present 2 unique cases of exertional supraspinatus syndrome related to
overexertion in 2 young men. In both cases, the diagnosis was delayed because the
symptom was nonspecific shoulder pain; however, progressive pain, an elevated
creatine kinase (CK) level, and either increased compartmental pressures or
findings on magnetic resonance imaging eventually led to the appropriate
diagnosis. CONCLUSION: The terms "supraspinatus compartment syndrome" and
"supraspinatus rhabdomyolysis" are inappropriately used interchangeably. We
believe that both conditions are part of a spectrum of pathology called
exertional supraspinatus syndrome. It is important to differentiate between these
conditions because a patient with supraspinatus compartment syndrome, which is
distinguished by elevated compartment pressures, requires an immediate
fasciotomy.
PMID- 29952778
TI - Early-Onset Fat Embolism Syndrome: A Case Report.
AB - CASE: We present the case of a 26-year-old otherwise healthy man with an isolated
tibial and fibular shaft fracture who developed signs of fat embolism syndrome
(FES) within 6 hours of injury and prior to any operative treatment. CONCLUSION:
General orthopaedists and traumatologists should be aware that the onset of FES
is not always delayed for several days, but can develop within 6 hours of injury.
After initiation of appropriate management, including respiratory support, our
patient did well. There was union of the fracture, and he was able to return to
work at 3 months postinjury.
PMID- 29952779
TI - Total Hip Arthroplasty in a Patient with Camurati-Engelmann Disease: A Case
Report.
AB - CASE: We review the case of a 44-year-old man with Camurati-Engelmann disease,
who presented with chronic right hip pain that did not improve following intra
articular hip injections. He was functionally debilitated because of the
worsening pain. Routine radiographs demonstrated severe right hip osteoarthritis
and severe diaphyseal sclerosis of the femur. To address the narrowed medullary
cavity, appropriate reaming of the diaphysis and broaching to fill the metaphysis
were performed. The patient underwent an uncemented total hip arthroplasty that
resulted in an excellent recovery with no complications. CONCLUSION: Uncemented
total hip arthroplasty serves as a good option for patients with hip
osteoarthritis secondary to Camurati-Engelmann disease. Anticipation of potential
operative challenges is the key to avoiding complications and achieving an
optimal, durable outcome.
PMID- 29952780
TI - Improvement During Inpatient Rehabilitation Among Older Adults With Guillain
Barre Syndrome, Multiple Sclerosis, Parkinson Disease, and Stroke.
AB - OBJECTIVE: The aim of the study was to quantify the improvement in independence
experienced by patients with the following diagnoses: Guillain-Barre syndrome,
multiple sclerosis, Parkinson disease, and stroke after inpatient rehabilitation.
DESIGN: Subjects who were admitted to inpatient rehabilitation hospitals in 2012
2013 with an incident diagnosis of the following: Guillain-Barre syndrome (n =
1079), multiple sclerosis (n = 1438), Parkinson disease (n = 11,834), or stroke
(n = 131,313), were included. The main outcome measure was improvement in
Functional Independence Measure scores on self-care, mobility, and cognition
during inpatient rehabilitation. We estimated percent improvement from a linear
mixed-effects model adjusted for patients' age, sex, race/ethnicity, comorbidity
count, diagnostic group (Guillain-Barre syndrome, multiple sclerosis, Parkinson
disease, and stroke), and admission score. RESULTS: All patient diagnostic groups
receiving inpatient rehabilitation improved across all three domains. The largest
adjusted percent improvements were observed in the mobility domain and the
smallest in the cognition domain for all groups. Percent improvement in mobility
ranged from 84.9% (multiple sclerosis) to 144.0% (Guillain-Barre syndrome), self
care from 49.5% (multiple sclerosis) to 84.1% (Guillain-Barre syndrome), and
cognition from 34.0% (Parkinson disease) to 51.7% (Guillain-Barre syndrome).
Patients with Guillain-Barre syndrome demonstrated the greatest percent
improvement across all three domains. CONCLUSIONS: Patients with Guillain-Barre
syndrome, multiple sclerosis, Parkinson disease, and stroke should improve during
inpatient rehabilitation but anticipated outcomes for patients with Guillain
Barre syndrome should be even higher.
PMID- 29952781
TI - Stimulant-induced Psychosis in the Postpartum Period: A Case Report.
AB - : Psychotic symptoms may emerge in up to 40% of people who misuse stimulants,
with physiological changes in the perinatal period potentially contributing to
the development of psychosis. In this report, we discuss the case of a woman
presenting with stimulant misuse, psychosis, and obsessive compulsive disorder
like symptoms in the postpartum period. We describe the patient's symptoms at
presentation, differential diagnoses, treatment course, and related challenges.
PMID- 29952782
TI - Effects of a Physical Activity and Sedentary Behavior Program on Activity Levels,
Stress, Body Size, and Sleep in Sedentary Korean College Students.
AB - This study examined the effects of a physical activity and sedentary behavior
program on physical activity, sedentary behavior, stress, body size, and sleep in
63 Korean college students. This study used a quasiexperimental approach with a
nonequivalent control group pretest-posttest design. The results showed that the
program increased physical activity and step counts and reduced sedentary
behavior, waist circumference, and stress levels.
PMID- 29952783
TI - Aspiration and Injection Techniques of the Lower Extremity.
AB - Orthopaedic surgeons frequently use aspirations and injections to both diagnose
and treat disorders of the lower extremity. Comprehensive knowledge of regional
anatomy, procedural indications, and appropriate techniques are essential.
Clinicians must be well versed in a range of musculoskeletal aspiration and
injection techniques, including patient positioning, equipment needs, injectable
solutions, aspirate analysis, and potential complications. Safe and effective
aspiration and injection techniques for the lower extremity, including the hip,
knee, foot, and ankle, are reviewed. Image guidance modalities include
fluoroscopy, ultrasonography, CT, and MRI.
PMID- 29952784
TI - Diagnosis and Treatment of Carpal Tunnel Syndrome in Low-prevalence
Circumstances.
PMID- 29952785
TI - Building on the HIV platform: tackling the challenge of noncommunicable diseases
among persons living with HIV.
AB - : The global HIV response has enabled access to prevention and treatment
interventions for millions of people around the world. This investment has
enabled the strengthening of health systems, which offers a remarkable
opportunity to integrate care for noncommunicable diseases for persons living
with HIV who are at risk for or have a noncommunicable disease.
PMID- 29952786
TI - Noncommunicable diseases among HIV-infected persons in low-income and middle
income countries: a systematic review and meta-analysis.
AB - OBJECTIVE: To appropriately identify and treat noncommunicable diseases (NCDs)
among persons living with HIV (PLHIV) in low-and-middle-income countries (LMICs),
it is imperative to understand the burden of NCDs among PLHIV in LMICs and the
current management of the diseases. DESIGN: Systematic review and meta-analysis.
METHODS: We examined peer-reviewed literature published between 1 January 2010
and 31 December 2016 to assess currently available evidence regarding HIV and
four selected NCDs (cardiovascular disease, cervical cancer, depression, and
diabetes) in LMICs with a focus on sub-Saharan Africa. The databases,
PubMed/MEDLINE, Cochrane Review, and Scopus, were searched to identify relevant
literature. For conditions with adequate data available, pooled estimates for
prevalence were generated using random fixed effects models. RESULTS: Six
thousand one hundred and forty-three abstracts were reviewed, 377 had potentially
relevant prevalence data and 141 were included in the summary; 57 were selected
for quantitative analysis. Pooled estimates for NCD prevalence were hypertension
21.2% (95% CI 16.3-27.1), hypercholesterolemia 22.2% (95% CI 14.7-32.1), elevated
low-density lipoprotein 23.2% (95% CI 15.2-33.6), hypertriglyceridemia 27.2% (95%
CI 20.7-34.8), low high-density lipoprotein 52.3% (95% CI 35.6-62.8), obesity
7.8% (95% CI 4.3-13.9), and depression 24.4% (95% CI 12.5-42.1). Invasive
cervical cancer and diabetes prevalence were 1.3-1.7 and 1.3-18%, respectively.
Few NCD-HIV integrated programs with screening and management approaches that are
contextually appropriate for resource-limited settings exist. CONCLUSION:
Improved data collection and surveillance of NCDs among PLHIV in LMICs are
necessary to inform integrated HIV/NCD care models. Although efforts to integrate
care exist, further research is needed to optimize the efficacy of these
programs.
PMID- 29952787
TI - Opportunities and challenges for evidence-informed HIV-noncommunicable disease
integrated care policies and programs: lessons from Malawi, South Africa,
Swaziland and Kenya.
AB - INTRODUCTION: Countries in sub-Saharan Africa (SSA) are recognizing the growing
dual burden of HIV and noncommunicable diseases (NCDs). This article explores the
availability, implementation processes, opportunities and challenges for policies
and programs for HIV/NCD integration in four SSA countries: Malawi, Kenya, South
Africa and Swaziland. METHODS: We conducted a cross-sectional analysis of current
policies and programs relating to HIV/NCD care integration from January to April
2017 using document review and expert opinions. The review focussed on
availability and content of relevant policy documents and processes towards
implementating national HIV/NCD integration policies. RESULTS: All four case
study countries had at least one policy document including aspects of HIV/NCD
care integration. Apart from South Africa that had a phased nation-wide
implementation of a comprehensive integrated chronic disease model, the three
other countries - Malawi, Kenya and Swaziland, had either pilot implementations
or nation-wide single-disease integration of NCDs and HIV. Opportunities for
HIV/NCD integration policies included: presence of overarching health policy
documents that recognize the need for integration, and coordinated action by
policymakers, researchers and implementers. Evidence gaps for cost-effectiveness,
effects of integration on key HIV and NCD outcomes and funding mechanisms for
sustained implementation of integrated HIV/NCD care strategies, were among
challenges identified. CONCLUSION: Policymakers in Malawi, Kenya, South Africa
and Swaziland have considered integration of NCD and HIV care but a lack of
robust evidence hampers large-scale implementation of HIV/NCD integration. It is
crucial for SSA Ministries of Health and throughout low-and-middle-income
countries to utilize existing opportunities and advocate for evidence-informed
HIV/NCD integration strategies.
PMID- 29952788
TI - Models of integration of HIV and noncommunicable disease care in sub-Saharan
Africa: lessons learned and evidence gaps.
AB - OBJECTIVE: To describe available models of HIV and noncommunicable disease (NCD)
care integration in sub-Saharan Africa (SSA). DESIGN: Narrative review of
published articles describing various models of HIV and NCD care integration in
SSA. RESULTS: We identified five models of care integration across various SSA
countries. These were integrated community-based screening for HIV and NCDs in
the general population; screening for NCDs and NCD risk factors among HIV
patients enrolled in care; integration of HIV and NCD care within clinics;
differentiated care for patients with HIV and/or NCDs; and population healthcare
for all. We illustrated these models with descriptive case studies highlighting
the lessons learned and evidence gaps from the various models. CONCLUSION:
Leveraging existing HIV infrastructure for NCD care is feasible with various
approaches possible depending on available program capacity. Process and clinical
outcomes for existing models of care integration are not yet described but are
urgently required to further advise policy decisions on HIV/NCD care integration.
PMID- 29952789
TI - Integrating cardiovascular disease risk factor screening into HIV services in
Swaziland: lessons from an implementation science study.
AB - OBJECTIVE: To study the feasibility of cardiovascular disease risk factor (CVDRF)
screening at an HIV clinic in Swaziland. METHODS: A sample of HIV-positive
patients at least 40 years on antiretroviral treatment was screened for
hypertension, diabetes, hyperlipidemia, and tobacco smoking. RESULTS: A total of
1826 patients were screened; 684 (39%) had at least one CVDRF. Screening volume
varied markedly, and was limited by staffing, space, and supplies. DISCUSSION:
CVDRF screening was feasible and prevalence of risk factors in people living with
HIV at least 40 years was high.
PMID- 29952790
TI - Strengthening the health workforce to support integration of HIV and
noncommunicable disease services in sub-Saharan Africa.
AB - OBJECTIVE: The successful expansion of HIV services in sub-Saharan Africa has
been a signature achievement of global public health. This article explores
health workforce-related lessons from HIV scale-up, their implications for
integrating noncommunicable disease (NCD) services into HIV programs, ways to
ensure that healthcare workers have the knowledge, skills, resources, and
enabling environment they need to provide comprehensive integrated HIV/NCD
services, and discussion of a priority research agenda. DESIGN AND METHODS: We
conducted a scoping review of the published and 'gray' literature and drew upon
our cumulative experience designing, implementing and evaluating HIV and NCD
programs in low-resource settings. RESULTS AND CONCLUSION: Lessons learned from
HIV programs include the role of task shifting and the optimal use of
multidisciplinary teams. A responsible and adaptable policy environment is also
imperative; norms and regulations must keep pace with the growing evidence base
for task sharing, and early engagement of regulatory authorities will be needed
for successful HIV/NCD integration. Ex-ante consideration of work culture will
also be vital, given its impact on the quality of service delivery. Finally,
capacity building of a robust interdisciplinary workforce is essential to foster
integrated patient-centered care. To succeed, close collaboration between the
health and higher education sectors is needed and comprehensive competency-based
capacity building plans for various health worker cadres along the education and
training continuum are required. We also outline research priorities for HIV/NCD
integration in three key domains: governance and policy; education, training, and
management; and service delivery.
PMID- 29952791
TI - Building reliable supply chains for noncommunicable disease commodities: lessons
learned from HIV and evidence needs.
AB - OBJECTIVE: Successful noncommunicable disease (NCD) management requires a
reliable supply chain. The objectives of this article are to examine lessons
learned from HIV supply chain initiatives, describe opportunities to advance
supply chain systems for NCD health commodities based on HIV supply chain
successes and identify areas where additional research is still needed for
reliable NCD supply chains in LMICs. DESIGN: We describe practical experiences
gained from developing HIV supply chain systems and how those lessons can be used
to inform NCD supply chain systems. METHODS: Supply chain challenges with HIV
commodities in low and middle-income countries (LMICs) are identified and
categorized using literature review and expert experiences. Solutions are
described on the basis of lessons learned from global HIV initiatives.
Opportunities to further advance NCD supply chain systems are recommended.
RESULTS: Supply chain challenges can be organized into two groups: 1) resource
mobilization and 2) resource utilization. Global HIV initiatives have responded
to resource mobilization challenges by increasing availability of funding,
filling human resource gaps, improving essential storage and creating better
transport mechanisms and information technology infrastructure. These initiatives
have assisted in better resource utilization by strengthening procurement
processes, standardizing and simplifying supply chain systems, reducing integrity
and security vulnerabilities and harnessing the power of better data. Advances
achieved through HIV initiatives are readily transferrable to NCD supply chains
with minimal additional investment. Research opportunities exist to identify the
most efficient and cost-effective ways to develop more reliable supply chains for
NCDs.
PMID- 29952792
TI - From HIV prevention to non-communicable disease health promotion efforts in sub
Saharan Africa: A Narrative Review.
AB - OBJECTIVE: To synthesize published literature on noncommunicable disease (NCD)
behavior change communication (BCC) interventions in sub-Saharan Africa (SSA)
among persons living with HIV (PLHIV) and in the general population to inform
efforts to adopt similar HIV and NCD BCC intervention activities. METHODS: We
conducted a literature review of NCD BCC interventions and included 20 SSA-based
studies. Inclusion criteria entailed describing a BCC intervention targeting any
four priority NCDs (cardiovascular disease, type 2 diabetes, cervical cancer, and
depression) or both HIV and any of the NCDs. The RE-AIM (Reach, Effectiveness,
Adoption, Implementation, and Maintenance) framework was used to assess potential
public health impact of these studies. We also solicited expert opinions from 10
key informants on the topic of HIV/NCD health promotion in five SSA countries.
RESULTS: The BCC interventions reviewed targeted multiple parts of the HIV and
NCD continuum at both individual and community levels. Various strategies (i.e.
health education, social marketing, motivational interviewing, mobile health, and
peer support) were employed. However, few studies addressed more than one
dimension of the RE-AIM framework. Opinions solicited from the key informants
supported the feasibility of integrating HIV and NCD BCC interventions in SSA
potentially improving access, service provision and service demand, especially
for marginalized and vulnerable populations. CONCLUSION: Although HIV/NCD
integration can improve effectiveness of preventive services at individual and
community levels, potential public health impact of such approaches remain
unknown as reach, adoptability, and sustainability of both integrated and
nonintegrated NCD BCC approaches published to date have not been well
characterized.
PMID- 29952793
TI - Global partnerships to support noncommunicable disease care in low and middle
income countries: lessons from HIV/AIDS.
AB - OBJECTIVE: The aim of this study was to identify lessons learned from
partnerships addressing the HIV/AIDS epidemic that can inform those needed to
mitigate the noncommunicable diseases (NCDs) epidemic in low and middle-income
countries (LMICs). DESIGN: We selected and analysed a convenience sample of
organizational partnerships developed to address the HIV/AIDS epidemic in LMICs,
focusing on their specific strategies and contributions. METHODS: A review of
published literature and website information pertaining to a convenience sample
of five global organizations and/or types of partnerships that provide support to
fight the HIV/AIDS epidemic was qualitatively analysed to assess key areas of
support provided to scale-up services in response to the HIV/AIDS epidemic.
RESULTS: Six topical areas of support were identified: HIV/AIDS service delivery;
enhancing comprehensive health systems capacity; operational and implementation
science research to improve care delivery; introducing and improving the
availability of new products; political advocacy; and early-stage planning for
sustainability and transition to more independent implementing-country delivery
programmes. These six areas of support were qualitatively assessed for identify a
focus, contributory or minimal contribution on the part of each of the
organizations and/or types of partnerships reviewed. CONCLUSION: No single global
partnership addresses the range of support needed to respond to the HIV/AIDS
epidemic, and this will likely be true for an effective response to the emerging
NCD epidemic. A range of coordinated financial and/or technical support as well
as lessons learned from global HIV/AIDS partnerships will be key to achieving an
effective response to the global NCD epidemic.
PMID- 29952794
TI - Costs and cost-effectiveness of HIV/noncommunicable disease integration in
Africa: from theory to practice.
AB - : The current article reviews economic aspects of selected HIV/noncommunicable
disease (NCD) service delivery integration programs to assess the efficiency of
integration in limited capacity settings. We define economies of scope and scale
and their relevance to HIV/NCD integration. We summarize the results of a
systematic review of cost and cost-effectiveness studies of integrated care,
which identified 12 datasets (nine studies) with a wide range of findings driven
by differences in research questions, study methods, and health conditions
measured. All studies were done in Africa and examined screening interventions
only. No studies assessed the cost of integrated, long-term disease management.
Few studies estimated the cost-effectiveness of integrated screening programs.
The additional cost of integrating NCD screening with HIV care platforms
represented a 6-30% increase in the total costs of the programs for noncancer
NCDs, with cervical cancer screening costs dependent on screening strategy. We
conducted 11 key informant interviews to uncover perceptions of the economics of
HIV/NCD integration. None of the informants had hard information about the
economic efficiency of integration. Most expected integrated care to be more cost
effective than current practice, though a minority thought that greater
specialization could be more cost-effective. In the final section of this
article, we summarize research needs and propose a 'minimum economic dataset' for
future studies. We conclude that, although integrated HIV/NCD care has many
benefits, the economic justification is unproven. Better information on the cost,
cost-effectiveness, and fiscal sustainability of integrated programs is needed to
justify this approach in limited-resource countries.
PMID- 29952795
TI - Implementation science for integration of HIV and non-communicable disease
services in sub-Saharan Africa: a systematic review.
AB - OBJECTIVE: As the burden of chronic non-communicable diseases (NCDs) rises across
sub-Saharan Africa (SSA), global donors and governments are exploring strategies
to integrate HIV and NCD care. Implementation science is an emerging research
paradigm that can help such programs achieve health impact at scale. We define
implementation science as a systematic, scientific approach to ask and answer
questions about how to deliver what works in populations who need it with greater
speed, appropriate fidelity, efficiency, and relevant coverage. We identified
achievements and gaps in the application of implementation science to HIV/NCD
integration, developed an HIV/NCD implementation science research agenda, and
detailed opportunities for capacity building and training. DESIGN: We conducted a
systematic review of the application of implementation science methods to
integrated HIV/NCD programs in SSA. METHODS: We searched PubMed, CINAHL,
PsycINFO, and EMBASE for evaluations of integrated programs in SSA reporting at
least one implementation outcome. RESULTS: We identified 31 eligible studies. We
found that most studies used only qualitative, economic, or impact evaluation
methods. Only one study used a theoretical framework for implementation science.
Acceptability, feasibility, and penetration were the most frequently reported
implementation outcomes. Adoption, appropriateness, cost, and fidelity were rare;
sustainability was not evaluated. CONCLUSIONS: Implementation science has a
promising role in supporting HIV/NCD integration, although its impact will be
limited unless theoretical frameworks, rigorous study designs, and reliable
measures are employed. To help support use of implementation science, we need to
build sustainable implementation science capacity. Doing so in SSA and supporting
implementation science investigators can help expedite HIV/NCD integration.
PMID- 29952796
TI - Building on the HIV chronic care platform to address noncommunicable diseases in
sub-Saharan Africa: a research agenda.
AB - OBJECTIVE: The remarkable progress made in confronting the global HIV epidemic
offers a unique opportunity to address the increasing threat of noncommunicable
diseases (NCDs). However, questions remain about how to enhance the HIV platforms
to deliver integrated HIV and NCD care to people living with HIV (PLHIV) in sub
Saharan Africa (SSA). We aimed to develop a priority research agenda to advance
this effort. METHODS: Researchers, policymakers, and implementers from the United
States and SSA conducted three scoping reviews on HIV/NCD prevention and care
focused on clinical, health system, and community levels. Based on the review
findings and expert inputs, we conducted iterative consensus-development
activities to generate a prioritized research agenda. RESULTS: Population-level
data on NCD prevalence among PLHIV in SSA are sparse. The review identified NCD
screening and management approaches that could be integrated into HIV programs in
SSA. However, few studies focused on the effectiveness, cost, and best practices
for integrated chronic care platforms, making it difficult to derive policy
recommendations. To address these gaps, we propose a prioritized research agenda
focused on developing evidence-based service delivery models, increasing human
capacity through workforce education, generating data through informatics
platforms and research, managing the medication supply chain, developing new
financing and sustainability models, advancing research-informed policy, and
addressing other crosscutting health system issues. CONCLUSION: Based on
collaborative, interdisciplinary efforts, a research agenda was developed to
provide guidance that advances efforts to adapt the current health system to
deliver integrated chronic care for PLHIV and the population at large.
PMID- 29952797
TI - Management of the Perimenopause.
AB - Perimenopause, or the menopausal transition, represents a period of time during
which newly arising symptoms can present complex management decisions for
providers. Many women present to care with complaints of hot flashes, vaginal and
sexual changes, altered mood and sleep, and changing bleeding patterns. The
effect of these symptoms on quality of life, even before a woman enters
menopause, can be significant. The appropriate evaluation and evidence-based
management of women in this transition is reviewed in this article. Two case
vignettes are used to highlight certain evaluation and treatment challenges.
PMID- 29952799
TI - Immune Cells on the Donor Corneal Endothelium After Corneal Transplantation.
AB - PURPOSE: The aim of this study was to investigate the existence of presumed
immune cells observed by contact specular microscopy in patients who underwent
penetrating keratoplasty (PK) and Descemet stripping automated endothelial
keratoplasty (DSAEK). METHODS: This cross-sectional study was conducted on
consecutive patients who underwent follow-up visits between January and March
2015 for previously performed PK or DSAEK. Presumed immune cell-suspected "cell
like white dots" were evaluated by scanning slit contact specular microscopy. The
association between the grading of presumed immune cells with clinical
parameters, such as corneal endothelial cell density, time after surgery, and the
titer of steroid administration, was also investigated. RESULTS: A total of 54
eyes of 54 patients who underwent PK (32 eyes/32 patients) and DSAEK (22 eyes/22
patients) were evaluated, and suspected immune cells were observed in all
patients. In the PK and DSAEK groups, the number of patients in the presumed
immune cell grades 1, 2, 3, and 4 were 19, 10, 2, and 1 and 10, 8, 2, and 2,
respectively (P = 0.663). No statistically significant association was found
between the immune cell grades and the clinical parameters. CONCLUSIONS: Immune
cells were observed on the corneal endothelial grafts in all 54 patients who
underwent PK or DSAEK. Although the number of immune cells varied between
patients and showed no correlation with clinical parameters, it would be
beneficial to conduct a future prospective study to analyze the effect of immune
cells on postoperative corneal endothelial cell loss.
PMID- 29952798
TI - Evaluation of the Effectiveness of Cross-Linking Combined With Photorefractive
Keratectomy for Treatment of Keratoconus.
AB - PURPOSE: To evaluate the effectiveness and safety of combined epithelium-off
cross-linking (CXL) with photorefractive keratectomy (CXL Plus) for correction of
the myopic and astigmatic components of keratoconus. METHODS: Seventy-nine eyes
of 46 patients who underwent CXL Plus were enrolled in this retrospective,
multicenter, noncomparative clinical study. Uncorrected distance visual acuity,
corrected distance visual acuity, refraction, keratometry, and pachymetry
measurements were recorded preoperatively and at 3, 6, 12, and 18 months during
follow-up. RESULTS: The mean (+/-SD) preoperative uncorrected distance visual
acuity and corrected distance visual acuity were 1.00 +/- 0.22 logarithm of the
minimum angle of resolution (logMAR) and 0.62 +/- 0.38 logMAR, respectively, and
improved to 0.71 +/- 0.36 logMAR and 0.32 +/- 0.18 logMAR postoperatively. The
mean k value, mean corneal thickness at the thinnest location, and mean myopic
and astigmatic components decreased from 46.58 +/- 0.97 D, 473 +/- 29 MUm, 3.65
+/- 1.72 D, and 1.83 +/- 0.69 D preoperatively to 43.79 +/- 1.17 D, 431 +/- 38
MUm, 1.02 +/- 0.78 D, and 1.15 +/- 0.26 D, respectively, during follow-up. Eleven
eyes had delayed epithelial healing, 2 had stromal opacities, 1 had primary
herpes simplex keratitis, and 5 showed progression of keratoconus. CONCLUSIONS:
CXL Plus improved the refractive status of keratoconus during 18 months of follow
up, despite its potential early postoperative complications of delayed epithelial
healing and corneal haze. CXL Plus reduced the myopic component more than the
astigmatic component of keratoconus. However, the safety and stability of the
procedure were offset by longer-term postoperative complications and a high rate
of postoperative progression of keratoconus.
PMID- 29952800
TI - Continuity of treatment with benzodiazepines in dementia patients: an analysis of
German health insurance claims data.
AB - Long-term treatment with benzodiazepines (BZD) should be avoided in dementia
patients because of an increased risk of adverse events. We evaluated how
continuously dementia patients were prescribed BZD over 12 months. For this
observational study, we used claims data from a large German public sickness fund
for 2014 and 2015, including patients with an incident diagnosis of dementia in
2014. The aim was to evaluate the continuity of treatment, the frequency of BZD
prescriptions and defined daily doses were evaluated. In total, 1298 (5.6%)
patients received 4.7+/-5.2 BZD prescriptions in 2015 on average. Thereof,
lorazepam (47.5%), oxazepam (18.6%), diazepam (14.5%), and bromazepam (12.2%)
were most often prescribed. 30.7% of the patients received at least one BZD
prescription in each quarter of 2015. Although the total number of patients
receiving BZD decreased in 2015, defined daily doses for single substances
remained mainly unchanged. The incident diagnosis of dementia was not associated
with modifications of prescription behavior. The treatment with BZD was not
discontinued in a large proportion of dementia patients, increasing the risk of
adverse events. Physicians' awareness of avoiding BZD should be improved and
further evidence for the appropriate treatment of psychiatric symptoms in
dementia (e.g. sleep disturbances, anxiety) is required.
PMID- 29952801
TI - Pump Position Impacts HeartMate II Left Ventricular Assist Device Thrombosis.
AB - The PREVENtion of HeartMate II pump Thrombosis through clinical management
(PREVENT) study was a multicenter, prospective investigation to evaluate the rate
of pump thrombosis (PT) with adoption of a uniform set of surgical and medical
practices for left ventricular assist device implantation. We sought to quantify
pump position at baseline and retrospectively define a pump position associated
with poor clinical outcomes. Chest x-rays at baseline were prospectively obtained
per protocol. Pump pocket depth, inflow cannula (IC) angle relative to the pump,
and IC angle relative to the vertical were measured. Pumps falling in the tail
ends of the IC angle and pump pocket depth distributions were categorized as
having an extreme pump position within the PREVENT study. Patients with extreme
pump position had a significantly higher risk of confirmed and suspected PT,
hemolysis, and elevated lactate dehydrogenase. In a multivariable analysis of
survival free of confirmed PT, extreme pump position was an independent risk
factor (hazard ratio = 3.6; 95% confidence interval = 1.5-8.9; p = 0.006) when
adjusting for differences in pump speed and anticoagulation level. Our analysis
shows that HeartMate II pump position at implant can significantly impact event
free survival and the incidence of adverse events at 6 months.
PMID- 29952802
TI - Shear-Mediated Platelet Activation Enhances Thrombotic Complications in Patients
With LVAD and Is Reversed After Heart Transplantation.
AB - We present a time-series analysis of shear-mediated platelet activation (SMPA) in
a patient supported by a left ventricular assist device (LVAD) who developed
recurrent thromboembolic events over the course of support. The patient showed
marked alterations of SMPA as quantified via the platelet activity state (PAS)
assay. At the time of a first pump thrombosis, PAS was equal to 16.2 +/- 2.1%,
indicating a significant level of SMPA. A moderate decrease of PAS was observed
30 days after pump exchange (PAS = 9.5 +/- 1.0%). A sudden PAS increase was
recorded after 60 days (PAS = 60.5 +/- 4.3%), and an ischemic stroke with
hemorrhagic transformation was subsequently diagnosed at 120 days after pump
exchange (PAS = 86.9 +/- 7.5%); high PAS values did not recover over time likely
because of sustained platelet activation from the inflammatory milieu caused by a
driveline infection occurred at 240 days of support (PAS = 84.4 +/- 7.3%).
Platelet activity state values were completely reversed after heart
transplantation (PAS = 0.6 +/- 0.1%), demonstrating resolution of SMPA. This
study provides further insight into our understanding of the pathogenesis of LVAD
thrombosis, addressing SMPA as a relevant key factor associated with thrombotic
complications. With the PAS assay, we have identified a reliable biomarker to
promote tailored pharmacological therapy for the prevention of thromboembolic
events in patients with LVADs.
PMID- 29952804
TI - Effects of Various Trajectories on Tissue Preservation in Cochlear Implant
Surgery: A Micro-Computed Tomography and Synchrotron Radiation Phase-Contrast
Imaging Study.
AB - OBJECTIVES: The purpose of this study was to evaluate the three-dimensional (3D)
anatomy and potential damage to the hook region of the human cochlea following
various trajectories at cochlear implantation (CI). The goal was to determine
which of the approaches can avoid lesions to the soft tissues, including the
basilar membrane and its suspension to the lateral wall. Currently, there is
increased emphasis on conservation of inner ear structures, even in nonhearing
preservation CI surgery. DESIGN: Micro-computed tomography and various CI
approaches were made in an archival collection of macerated and freshly fixed
human temporal bones. Furthermore, synchrotron radiation phase-contrast imaging
was used to reproduce the soft tissues. The 3D anatomy was investigated using
bony and soft tissue algorithms, and influences on inner ear structures were
examined. RESULTS: Micro-computed tomography with 3D rendering demonstrated the
topography of the round window (RW) and osseous spiral laminae, while synchrotron
imaging allowed reproduction of soft tissues such as the basilar membrane and its
suspension around the RW membrane. Anterior cochleostomies and anteroinferior
cochleostomies invariably damaged the intracochlear soft tissues while inferior
cochleostomies sporadically left inner ear structures unaffected. CONCLUSIONS:
Results suggest that cochleostomy approaches often traumatize the soft tissues at
the hook region at CI surgery. For optimal structural preservation, the RW
approach is, therefore, recommended.
PMID- 29952805
TI - Cochlear Mechanisms and Otoacoustic Emission Test Performance.
AB - OBJECTIVES: This study aims to determine the impact of controlling cochlear
source mechanism on the accuracy with which auditory status is identified using
otoacoustic emissions (OAEs) in two groups of subjects with normal hearing (NH)
and subjects with mild to moderate hearing loss. DESIGN: Data were collected from
212 subjects with NH and with mild to moderate hearing loss who fell into two
categories based on a distortion product OAE (DPOAE) screening protocol: the
uncertain-identification group (where errors were likely) and the certain
identification group (where errors were unlikely). DPOAE fine-structure patterns
were recorded at intervals surrounding f2 = 1, 2 and 4 kHz (f2/f1 ratio = 1.22),
with L2 = 35, 45, and 55 dB SPL (L1/L2 ratio = 10 dB). The discrete cosine
transform was used to smooth fine structure, limiting the source contribution to
the distortion source only. Reflection-source OAEs were also recorded using
amplitude-modulated stimulus frequency OAEs (AM-SFOAE). Area under the relative
operating characteristic (AROC) curve was used to quantify test accuracy when the
source contribution was controlled versus the condition where both sources
contribute. Additionally, failure rate, fixed at 5% for NH ears, as a function of
behavioral-threshold category was evaluated. RESULTS: When data for the entire
subject group were examined, reducing the reflection-source contribution to the
DPOAE did not result in better test performance than the best control condition
at any frequency tested. When the subjects with NH were restricted to those with
confirmed fine structure, AROC analyses indicated that reducing the reflection
source contribution resulted in several small increases in the accuracy (2%-5%)
with which auditory status was identified relative to the best control condition.
This improvement was observed for the lowest stimulus levels (i.e., L2 = 35 or 45
dB SPL). In this subset of subjects, distortion-source DPOAEs resulted in more
accurate identification of mild hearing loss for a fixed false-positive rate of
5% in NH ears at lower L2's, conditions with poor accuracy in the larger group of
subjects. The impact of controlling the source contribution on the identification
of moderate losses was less clear in the reduced subject group, with some
conditions where the distortion-source DPOAE was more accurate than the control
condition and other conditions where there was no change. There was no evidence
that reflection-source AM-SFOAEs more accurately identified ears with hearing
loss when compared to any of the DPOAE conditions in either the large or reduced
group of subjects. CONCLUSION: While improvements in test accuracy were observed
for some subjects and some conditions (e.g., mild hearing losses and low stimulus
levels in the reduced subset of subjects), these results suggest that restricting
cochlear source contribution by "smoothing" DPOAE fine structure is not expected
to improve DPOAE test accuracy in a general population of subjects. Likewise,
recording reflection-source OAEs using the AM-SFOAE technique would not be
expected to more accurately identify hearing status compared to mixed- or single
source DPOAEs.
PMID- 29952806
TI - Prognostic Value of the 6-Min Walk Test After Open-Heart Valve Surgery:
EXPERIENCE OF A CARDIOVASCULAR REHABILITATION PROGRAM.
AB - PURPOSE: This single-center retrospective analysis aimed to evaluate the
prognostic relevance of 6-min walk test (6MWT) in patients admitted to an in
hospital cardiovascular rehabilitation program after open-heart valve surgery.
METHODS: One hundred one patients able to perform a 6MWT within the first week of
admission (time after surgery: 16 +/- 8 d) were included (age 68 +/- 11 y; 55%
female; median left ventricular ejection fraction 55% [interquartile range: 50
60]; 51% after aortic valve surgery). Study endpoints were cardiovascular death
and the combined outcome of cardiovascular death/cardiac hospitalization.
Univariate and multivariate analyses were performed to analyze predictive value
of the 6MWT. RESULTS: After a median follow-up of 27 mo, cardiovascular mortality
was 9.9% while combined endpoint occurrence was 33%. Patients experiencing study
endpoints had lower left ventricular ejection fraction, higher N-terminal
prohormone of brain natriuretic peptide serum levels, and longer in-hospital stay
(all P < .05). The 6MWT distance was a significant predictor of cardiovascular
death (hazard ratio [HR] = 0.89, 95% CI: 0.81-0.97, P = .007) and cardiac
hospitalizations (HR = 0.95, 95% CI: 0.90-0.99, P = .02). Even after adjusting
for the relevant confounding variables of cardiovascular death and cardiac
hospitalization, the adjusted HR = 0.88, 95% CI: 0.75-0.98, P = .028 and adjusted
HR = 0.95, 95% CI: 0.90-0.99, P = .05, respectively. CONCLUSIONS: In patients
admitted to an in-hospital cardiovascular rehabilitation program after open-heart
valve surgery, 6MWT proved to be an independent prognostic tool, potentially
allowing identification of high-risk patients for whom a more intensive and
tailored in-hospital cardiovascular rehabilitation program should be designed and
implemented in order to avoid unfavorable cardiovascular events.
PMID- 29952807
TI - Characterizing and Comparing Acute Responses of Blood Pressure, Heart Rate, and
Forearm Blood Flow to 2 Handgrip Protocols.
AB - PURPOSE: Growing evidence supports handgrip exercise training for reducing
resting blood pressure (BP), with inconsistent exercise protocols reported
throughout the literature. To verify safety of such protocols, real-time
cardiovascular responses must be assessed. Consequently, this research sought to
evaluate the acute impact of dissimilar handgrip protocols on the cardiovascular
responses of BP, heart rate (HR), and forearm blood flow. METHODS: Using a
randomized intraindividual crossover design, 20 post-menopausal women completed 2
distinct handgrip protocols compared with a nonexercise control: 4 * 2-min
sustained grips at 30% moderate intensity with 1-min rest between sets (ZONA),
and 32 * 5-sec intermittent grips at maximal intensity with 5-sec rest between
sets (MINT). Cardiovascular responses were measured throughout exercise and post
exercise recovery. RESULTS: Compared to ZONA, the MINT protocol required less
time and less exercise effort, yet caused greater average BP perturbations
(systolic, MINT: 16.9 +/- 12.9 mm Hg, ZONA: 7.9 +/- 11.6 mm Hg; diastolic, MINT:
8.7 +/- 7.2 mm Hg, ZONA: 4.5 +/- 4.9 mm Hg) (P < .05), with peak BP changes far
below published safety guidelines. Average HR responses were similarly elevated
between protocols (MINT: 5.4 +/- 4.9 beats/min, ZONA: 3.4 +/- 3.6 beats/min).
Post-exercise recovery of BP and HR occurred swiftly following MINT while
remaining elevated following ZONA. CONCLUSIONS: Handgrip exercise protocols with
distinct design features (ie, grip intensity, grip strategy, and exercise
duration) cause dissimilar acute cardiovascular responses. Careful and controlled
attention should be directed toward determining how such acute dissimilarities
influence corresponding training outcomes. Given the confirmed safety of acute BP
perturbations, future researchers can have confidence in prescribing even the
high-intensity MINT protocol for at-home, unsupervised activity.
PMID- 29952808
TI - Physiological Responses and Dynamic Hyperinflation Induced by Unsupported Arm
Activities Involved in Multiple-Task Activities of Daily Living Test in Patients
With COPD.
AB - PURPOSE: This study aimed to analyze the isolated role of unsupported arm
activities and the physiological responses and dynamic hyperinflation (DH)
induced by activities of daily living in patients with chronic obstructive
pulmonary disease. Physiological responses and DH were compared using the Glittre
activities of daily living test (TGlittre) and a modified protocol that
emphasized unsupported arm activities and excluded squats and bending down to
move objects on shelves (TGlittre-M). Data were also compared from the isolated
shelf tasks of TGlittre (TSHELF) and TGlittre-M (TSHELF-M). METHODS: This cross
sectional study included 30 patients with chronic obstructive pulmonary disease
who performed the TGlittre, TGlittre-M, TSHELF and TSHELF-M. The physiological
responses were evaluated during the 4 protocols and inspiratory capacity was
measured before and immediately after the tests for evaluation of DH. RESULTS:
Patients had higher oxygen uptake, ventilatory demand, dyspnea, and DH in the
TGlittre than in the TGlittre-M (mean differences: 123 +/- 119 mL/min; 0.11 +/-
0.10, 1 [-1 to 3], and - 0.14 +/- 0.22, respectively; P < .05 for all). Oxygen
uptake, ventilatory demand, and dyspnea were also higher in the TSHELF than in
the TSHELF-M (mean differences: 408 +/- 185 mL/min; 0.26 +/- 0.17; 1 [-1 to 3],
respectively; P < .05 for all). However, DH was similar for both tasks (P > .05).
CONCLUSIONS: In patients with chronic obstructive pulmonary disease, the
physiological demands during unsupported arm activities were lower than during
the task performed with squatting and bending down; however, the magnitude of DH
did not differ between them. These results suggest that the isolated arm
activities contribute less to the TGlittre's physiological requirement than the
lower-limb and trunk activities.
PMID- 29952809
TI - Pulmonary Rehabilitation Only Versus With Nutritional Supplementation in Patients
With Bronchiectasis: A RANDOMIZED CONTROLLED TRIAL.
AB - PURPOSE: Pulmonary rehabilitation (PR) is recommended for bronchiectasis, but
there is little evidence of its efficacy in these patients. The aim of this study
was to assess the effect of PR in normally nourished patients with noncystic
fibrosis bronchiectasis compared with the effect of PR plus an oral nutritional
supplement (PRONS). METHODS: A single-center randomized controlled trial,
parallel treatment design in which participants were randomly assigned to receive
PR for 12 wk or PR plus a high-protein nutritional supplement enriched with beta
hydroxy-beta-methylbutyrate. Outcome assessments were performed at baseline, 12
and 24 wk including cardiopulmonary exercise testing, health-related quality of
life (HRQOL), bronchorrhea, dyspnea, psychological symptoms, spirometry, and
exacerbations. RESULTS: Thirty patients were randomized into 2 groups of 15
participants. In both groups, cardiopulmonary exercise testing, HRQOL, dyspnea,
and spirometry parameters significantly increased from baseline at 3 and/or 6 mo.
CONCLUSION: PR improved exercise capacity, HRQOL, and respiratory parameters. The
use of PRONS did not have a significant effect on the results.
PMID- 29952810
TI - Exertional Oxygen Requirements During Exercise Training in Advanced Interstitial
Lung Disease.
AB - PURPOSE: Little is known about the oxygen requirements during physical exertion
or exercise in individuals with interstitial lung disease (ILD). This study
examined exertional oxygen requirements, the relationships between exertional
oxygen use, exercise capacity and aerobic training parameters, and predictors of
change in exertional oxygen requirements during pulmonary rehabilitation (PR).
METHODS: A retrospective study of lung transplant candidates with advanced ILD
who underwent at least 4 wk of outpatient PR between 2004 and 2014 was
undertaken. Data were extracted at baseline, 4 wk, and 6 mo. Exertional oxygen
was prescribed during PR to support continuous, moderate-intensity aerobic
training. RESULTS: The study cohort (n = 375) had a median age of 61 y (55-66 y),
were 57% male, and most were diagnosed with idiopathic pulmonary fibrosis (n =
214). A variety of oxygen delivery systems were used and exertional oxygen
requirements increased after 4 wk (0.5 [0.4-0.6] vs 0.5 [0.4-0.73], P < .001, n =
375) and 6 mo (0.44 [0.36-0.5] vs 0.5 [0.4-0.55], P < .001, n = 196) of PR. A
higher exertional oxygen requirement was associated with lower 6-min walk
distance and lower aerobic training intensity at all time points. There were no
identified predictors of the change in exertional oxygen requirements.
CONCLUSIONS: Individuals with advanced ILD had high exertional oxygen
requirements to participate in moderate-intensity aerobic training, which
increased over time. Exertional oxygen needs may affect exercise prescription and
response during PR in ILD patients.
PMID- 29952811
TI - Characteristics, Therapeutic Needs, and Scope of Patients With a Continuous-Flow
Left Ventricular Device Entering Cardiac Rehabilitation: A RETROSPECTIVE
ANALYSIS.
AB - BACKGROUND: With an increasing number of left ventricular assist devices (LVADs)
being implanted, the need for adequate cardiac rehabilitation (CR) regimens
meeting the special needs of these patients arises. Only a few studies have
reported experience gained on this topic. Structured CR strategies are poorly
implemented. The aim was to evaluate the characteristics, therapeutic needs, and
scope of LVAD patients at admission to CR within a greater cohort in order to
identify their special CR needs. METHODS: Retrospective single-center study; 69
LVAD patients (50.7 +/- 13.6 y; 59 male; 48 HVAD; 21 HeartMate II) who completed
first inpatient CR were included. Patient records were used to document relevant
medical information (including the results of a 6-min walk test and a maximal
isometric strength test for quadriceps femoral muscles in both legs) and the
International Classification of Functioning, Disability and Health for
classification of health and health-related domains. RESULTS: Patient
characteristics demonstrated a heterogeneous group: CR was started 44 +/- 38.6 d
after implantation; CR duration was 28 +/- 9.7 d. Despite similar etiology,
physical and psychological condition was diverse, although, overall a high degree
of impairment was present, especially in the body function (79.7%) and activity
and participation (95.7%) domains. The results demonstrated the need for a highly
individualized approach in the somatic and also in the education, psychosocial,
and social therapeutic regimes. CONCLUSION: The results demonstrate a
heterogeneous group with a high level of impairment and special needs in many CR
domains. The development and evaluation of a special highly individualized
approach of CR, which meets the special needs of these patients, is needed.
PMID- 29952812
TI - Objectively Measured Changes in Physical Activity and Sedentary Behavior in
Cardiac Rehabilitation: A PROSPECTIVE COHORT STUDY.
AB - PURPOSE: Physical inactivity and sedentary behavior (SB) are independent risk
factors for cardiovascular disease and all-cause mortality. No studies appear to
have investigated whether SB in cardiac rehabilitation (CR) participants changes
over time. The aim of this study was to objectively assess physical activity (PA)
and SB of CR participants over 6 wks. METHODS: Using a prospective cohort study
design, 72 CR participants, age = 64.2 +/- 9.6 y (mean +/- standard deviation
[SD]) (79% male), wore an ActiGraph ActiSleep accelerometer for 7 consecutive
days at the beginning and end of a 6-wk program to assess daily minutes of
moderate-to-vigorous PA (MVPA) and SB (<100 counts/min). Other outcomes collected
were self-reported MVPA (Active Australia Survey) and SB (Past-Day Adults'
Sedentary Time Questionnaire), body mass index, waist-to-hip ratio, lipid
profile, blood glucose level, quality of life (MacNew), exercise capacity (6-min
walk test), anxiety and depression (Hospital Anxiety and Depression Scale).
RESULTS: Time spent in MVPA and SB did not change over 6 wks. However, exercise
capacity and light-intensity PA significantly improved (P < .01). On average,
participants spent 11.8 +/- 1.1 hr daily in SB, with 9.5 +/- 14.7 min daily in
MVPA at the end of the CR program. There was some evidence that males and females
had different movement patterns. CONCLUSIONS: Levels of PA are low and SB is high
in CR participants despite changes in exercise capacity over 6 wks. Participants
in CR did increase their PA but only in the light-intensity range. Alternative
approaches in CR should be considered to encourage participants to move more and
sit less.
PMID- 29952813
TI - Zumba Fitness and Women's Cardiovascular Health: A SYSTEMATIC REVIEW.
AB - PURPOSE: Zumba fitness (ZF) is a well-known exercise program involving dance and
fitness. Despite its increasing popularity, no analysis has been conducted on
studies focusing on the cardiovascular (CV) profile of women who performed this
activity. The aim of this systematic review is to provide insights into the
impact of ZF on women's CV health. METHODS: Five clinical databases were
searched. To be included, the articles had to include (1) women with or without
CV risk factors (CVRF) and (2) CV-related outcomes resulting from a ZF program.
RESULTS: Ten studies (322 women; 181 healthy, 141 with CVRF) were included. In
healthy women, low absolute effect sizes for maximal oxygen uptake (VO2max),
anthropometric and body composition profile after 8 and 12 wk of ZF were found
compared with nonparticipants. Moderate to large absolute effect sizes were
recorded for VO2max and body composition following 40 wk of ZF. Findings proved
promising but less consistent for ZF studies involving women with CVRF due to the
absence of control groups. CONCLUSIONS: Data describe ZF as feasible for healthy
women and a promising fitness option for those with CVRF. Because of the low
quality of the studies on women with CVRF and the overall small sample size along
with discrepancies such as the average length of the studies on healthy women,
cautious interpretation of the findings is recommended. Further investigations
with a standardized design are needed to verify whether ZF may be considered as
an alternative fitness option in primary prevention of CV disease in women.
PMID- 29952814
TI - Disrupted metabolic and functional connectivity patterns of the posterior
cingulate cortex in cirrhotic patients: a study combining magnetic resonance
spectroscopy and resting-state functional magnetic resonance imaging.
AB - The association between metabolic activity and functional coupling of the
posterior cingulate cortex (PCC) in cirrhotic patients remains undefined.
Therefore, this study aimed to assess the association of functional coupling with
metabolic patterns of PCC in resting cirrhotic patients. Twenty-six cirrhotic
patients, including 10 with hepatic encephalopathy (HE) and 16 without HE, were
assessed, alongside 21 control participants. Single-voxel proton magnetic
resonance spectroscopy (MRS) of the PCC and resting-state functional MRI (rs
fMRI) were performed on a 3.0-T MR scanner. The ratios of all metabolites to
creatine (Cr) and rs-fMRI parameters [including amplitude of low-frequency
fluctuation (ALFF), node degree (Ki), and betweenness centrality (Bi)] were
evaluated by analysis of variance. Associations of metabolite ratios with rs-fMRI
parameters and venous ammonia were determined by Pearson's correlation analysis.
Lower chlorine (Cho)/Cr (0.6+/-0.2 vs. 0.9+/-0.1, P<0.001) and higher ALFF (1.3+/
0.5 vs. 1.1+/-0.3, P=0.01) were found in cirrhotic patients in comparison with
controls. In cirrhotic patients, the ALFF values correlated negatively with
Cho/Cr (r=-0.397, P=0.044). Meanwhile, Bi values showed positive associations
with glutamine+glutamate/Cr (r=0.500, P=0.009) and N-acetyl aspartate/Cr
(r=0.581, P=0.006). In the HE subgroup, Ki correlated positively with Cho/Cr
(r=0.867, P=0.001). In cirrhotic patients without HE, Bi values showed a high
positive correlation with glutamate+glutamine/Cr (r=0.690, P=0.013). These
findings suggest a close association between metabolic activity and functional
coupling of the PCC in cirrhotic patients, especially those with HE, whose node
degree of the PCC shows an overt positive correlation with Cho/Cr.
PMID- 29952815
TI - Mannitol in Critical Care and Surgery Over 50+ Years: A Systematic Review of
Randomized Controlled Trials and Complications With Meta-Analysis.
AB - OBJECTIVE: Despite clinical use spanning 50+ years, questions remain concerning
the optimal use of mannitol. The published reviews with meta-analysis frequently
focused on mannitol's effects on a specific physiological aspect such as
intracranial pressure (ICP) in sometimes heterogeneous patient populations. A
comprehensive review of mannitol's effects, as well as side effects, is needed.
METHODS: The databases Medline (OvidSP), Embase (OvidSP), and NLM PubMed were
systematically searched for randomized controlled trials (RCTs) comparing
mannitol to a control therapy in either the critical care or perioperative
setting. Meta-analysis was performed when feasible to examine mannitol's effects
on outcomes, including ICP, cerebral perfusion pressure, mean arterial pressure
(MAP), brain relaxation, fluid intake, urine output, and serum sodium. Systematic
literature search was also performed to understand mannitol-related
complications. RESULTS: In total 55 RCTs were identified and 7 meta-analyses were
performed. In traumatic brain injury, mannitol did not lead to significantly
different MAP (SMD [95% confidence interval], CI)=-3.3 [-7.9, 1.3] mm Hg; P=0.16)
but caused significantly different serum sodium concentrations (SMD [95% CI]=-8.0
[-11.0, -4.9] mmol/L; P<0.00001) compared with hypertonic saline. In elective
craniotomy, mannitol was less likely to lead to satisfactory brain relaxation (RR
[95% CI]=0.89 [0.81, 0.98]; P=0.02), but was associated with increased fluid
intake (SMD [95% CI]=0.67 [0.21, 1.13] L; P=0.004), increased urine output (SMD
(95% CI)=485 (211, 759) mL; P=0.0005), decreased serum sodium concentration (SMD
[95% CI]=-6.2 [-9.6, -2.9] mmol/L; P=0.0002), and a slightly higher MAP (SMD [95%
CI]=3.3 [0.08, 6.5] mm Hg; P=0.04) compared with hypertonic saline. Mannitol
could lead to complications in different organ systems, most often including
hyponatremia, hyperkalemia, and acute kidney injury. These complications appeared
dose dependent and had no long-term consequences. CONCLUSIONS: Mannitol is
effective in accomplishing short-term clinical goals, although hypertonic saline
is associated with improved brain relaxation during craniotomy. Mannitol has a
favorable safety profile although it can cause electrolyte abnormality and renal
impairment. More research is needed to determine its impacts on long-term
outcomes.
PMID- 29952816
TI - Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High
Risk Deceased Donor Human Kidneys for Transplantation.
AB - BACKGROUND: Despite careful clinical examination, procurement biopsy and
assessment on hypothermic machine perfusion (HMP), a significant number of
potentially useable deceased donor kidneys will be discarded because they are
deemed unsuitable for transplantation. Ex vivo normothermic perfusion (EVNP) may
be useful as a means to further assess high-risk kidneys to determine suitability
for transplantation. METHODS: From June 2014 to October 2015, 7 kidneys (mean
donor age 54.3 years and KDPI 79%) that were initially procured with the
intention to transplant were discarded based on a combination of clinical
findings, suboptimal biopsies, long cold ischemia time and/or poor hypothermic
perfusion parameters. They were subsequently placed on EVNP using oxygenated
packed red blood cells and supplemental nutrition for a period of 3 hours.
Continuous hemodynamic and functional parameters were assessed. RESULTS: After a
mean cold ischemia time (CIT) of 43.7 hours, all 7 kidneys appeared viable on
EVNP with progressively increasing renal blood flow over the 3-hour period of
perfusion. Five of the 7 kidneys had excellent macroscopic appearance, rapid
increase in blood flow to 200-250 ml/min, urine output of 40-260 ml/hr and
increasing creatinine clearance. CONCLUSIONS: Favorable perfusion characteristics
and immediate function after a 3 hour course of EVNP suggests that high-risk
kidneys subjected to long CIT may have been considered for transplantation. The
combined use of ex vivo hypothermic and normothermic perfusion may be a useful
strategy to more adequately assess and preserve high-risk kidneys deemed
unsuitable for transplantation. A clinical trial will be necessary to validate
the usefulness of this approach.This is an open-access article distributed under
the terms of the Creative Commons Attribution-Non Commercial-No Derivatives
License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work
provided it is properly cited. The work cannot be changed in any way or used
commercially without permission from the journal.
PMID- 29952818
TI - Incisional Nociceptive Input Impairs Attention-related Behavior and Is Associated
with Reduced Neuronal Activity in the Prefrontal Cortex in Rats.
AB - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
BACKGROUND:: Cognitive capacity may be reduced from inflammation, surgery,
anesthesia, and pain. In this study, we hypothesized that incision-induced
nociceptive input impairs attentional performance and alters neuronal activity in
the prefrontal cortex. METHODS: Attentional performance was measured in rats by
using the titration variant of the 5-choice serial reaction time to determine the
effect of surgical incision and anesthesia in a visual attention task. Neuronal
activity (single spike and local field potentials) was measured in the medial
prefrontal cortex in animals during the task. RESULTS: Incision significantly
impaired attention postoperatively (area under curve of median cue duration-time
97.2 +/- 56.8 [n = 9] vs. anesthesia control 25.5 +/- 14.5 s-days [n = 9], P =
0.002; effect size, eta = 0.456). Morphine (1 mg/kg) reduced impairment after
incision (area under curve of median cue duration-time 31.6 +/- 36.7 [n = 11] vs.
saline 110 +/- 64.7 s-days [n = 10], P < 0.001; eta = 0.378). Incision also
decreased cell activity (n = 24; 1.48 +/- 0.58 vs. control, 2.93 +/- 2.02
bursts/min; P = 0.002; eta = 0.098) and local field potentials (n = 28; eta =
0.111) in the medial prefrontal cortex. CONCLUSIONS: These results show that
acute postoperative nociceptive input from incision reduces attention-related
task performance and decreases neuronal activity in the medial prefrontal cortex.
Decreased neuronal activity suggests nociceptive input is more than just a
distraction because neuronal activity increases during audiovisual distraction
with similar behavioral impairment. This suggests that nociceptive input and the
medial prefrontal cortex may contribute to attentional impairment and mild
cognitive dysfunction postoperatively. In this regard, pain may affect
postoperative recovery and return to normal activities through attentional
impairment by contributing to lapses in concentration for routine and complex
tasks.
PMID- 29952817
TI - Effect of Thoracic Epidural Anesthesia in a Rat Model of Phrenic Motor Inhibition
after Upper Abdominal Surgery.
AB - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
BACKGROUND:: One important example of impaired motor function after surgery is
diaphragmatic dysfunction after upper abdominal surgery. In this study, the
authors directly recorded efferent phrenic nerve activity and determined the
effect of the upper abdominal incision. The authors hypothesized that phrenic
motor output would be decreased after the upper abdominal incision; it was also
hypothesized that blocking sensory input from the incision using thoracic
epidural anesthesia would diminish this incision-induced change in phrenic motor
activity. METHODS: Efferent phrenic activity was recorded 1 h to 10 days after
upper abdominal incision in urethane-anesthetized rats. Ventilatory parameters
were measured in unanesthetized rats using whole-body plethysmography at multiple
time points after incision. The authors then determined the effect of thoracic
epidural anesthesia on phrenic nerve activity and ventilatory parameters after
incision. RESULTS: Phrenic motor output remained reduced by approximately 40% 1 h
and 1 day after incision, but was not different from the sham group by
postoperative day 10. One day after incision (n = 9), compared to sham-operated
animals (n = 7), there was a significant decrease in spike frequency area-under
the-curve (median [interquartile range]: 54.0 [48.7 to 84.4] vs. 97.8 [88.7 to
130.3]; P = 0.0184), central respiratory rate (0.71 [0.63 to 0.79] vs. 0.86 [0.82
to 0.93]/s; P = 0.0460), and inspiratory-to-expiratory duration ratio (0.46 [0.44
to 0.55] vs. 0.78 [0.72 to 0.93]; P = 0.0023). Unlike humans, a decrease, not an
increase, in breathing frequency has been observed after the abdominal incision
in whole-body plethysmography. Thoracic epidural anesthesia attenuated the
incision-induced changes in phrenic motor output and ventilatory parameters.
CONCLUSIONS: Upper abdominal incision decreased phrenic motor output and
ventilatory parameters, and this incision-induced impairment was attenuated by
thoracic epidural anesthesia. The authors' results provide direct evidence that
afferent inputs from the upper abdominal incision induce reflex inhibition of
phrenic motor activity.
PMID- 29952819
TI - Trends in Glaucoma Surgical Procedures in Portugal: A 16-Year Nationwide Study
(2000-2015).
AB - PURPOSE: Glaucoma leads as the first cause of irreversible blindness. The number
of patients will greatly increase in upcoming years and changes will have to be
accomplished to cope with those numbers. As such, data are important to
understand the effect of new policies introduced in glaucoma management. Only few
countries have described their glaucoma surgical profile and, in Europe, only the
United Kingdom described the last 15 years. The aim of this study is to assess
the glaucoma surgical profile and its changes in mainland Portugal from 2000 to
2015. METHODS: Retrospective database analysis of inpatient and surgical
outpatients' episodes of all public hospitals in mainland Portugal was performed.
The annual absolute numbers of ophthalmic procedures, as well as their surgical
rate (per 100,000 inhabitants) were calculated. RESULTS: Glaucoma patients
undergoing glaucoma procedures were 67+/-14 years old and 50% were female. During
the study period there was an increase in the number and surgical rate of
glaucoma procedures. Trabeculectomy showed a stable surgical rate (7 per 100,000
inhabitants) despite a reduction in terms of relative weight among glaucoma
procedures. At the same time, the surgical rate of glaucoma drainage devices and
cyclophotoablation increased, while remaining stable for cyclocryoablation.
CONCLUSIONS: In Portugal, trabeculectomy had a stable surgical rate throughout
the study period, being the most performed glaucoma surgical procedure. Other
surgeries, like glaucoma drainage devices and cyclophotoablation are gaining
ground among glaucoma specialists. Our results match what has been published by
other countries worldwide and can be used to achieve a better health planning.
PMID- 29952820
TI - Juvenile Open Angle Glaucoma With Nonbullous Congenital Ichthyosiform
Erythroderma.
AB - INTRODUCTION: Glaucoma in patients with nonbullous congenital ichthyosiform
erythroderma (NBCIE) is a rare entity that has not been described in a
histologically confirmed case. We present a unique case of coexisting glaucoma,
ichthyosis, and dwarfism that has not been previously described. METHODS: We
present a case of NBCIE with glaucoma and dwarfism that presented to our
outpatient department. The patient was referred for watering and photophobia that
were due to an epithelial defect that was subsequently managed conservatively.
Investigations revealed the existence of a constellation of findings that are
presented here. RESULTS: NBCIE, glaucoma, and dwarfism represent a spectrum of
diseases that seem to have a syndromic association. More gene linkage-based
analysis are, however, needed to further confirm our observations. CONCLUSIONS:
NBCIE, glaucoma, and dwarfism can often occur together and need to be assessed
and managed individually. Early diagnosis of this spectrum can help improve
patient management and quality of life. Dermatologists must get an ocular
examination conducted for icthyoses patients.
PMID- 29952821
TI - Reduced Cerebral Blood Flow in the Visual Cortex and Its Correlation With
Glaucomatous Structural Damage to the Retina in Patients With Mild to Moderate
Primary Open-angle Glaucoma.
AB - PURPOSE: Altered ocular and cerebral vascular autoregulation and vasoreactivity
have been demonstrated in patients with primary open-angle glaucoma (POAG). In
the present study, we investigated the correlations between reduced cerebral
blood flow (CBF) in early and higher-tier visual cortical areas and glaucomatous
changes in the retinas of patients with mild to moderate POAG. PATIENTS AND
METHODS: 3-dimensional pseudocontinuous arterial spin labelling magnetic
resonance imaging at 3 T was performed in 20 normal controls and 15 mild to
moderate POAG patients. Regions of interest were selected based on the Population
Average, Landmark- and Surface-based (PALS) atlas of the human cerebral cortex.
Arterial spin labelling-measured CBF values were extracted in the early and
higher-tier visual cortical areas and were compared between patients and controls
using a 2-sample t test. Pearson correlation analyses were used to assess the
correlations between reduced CBF and cup-to-disc ratio, retinal nerve fiber layer
thickness, and ganglion cell complex thickness. RESULTS: Reduced CBF in early
visual cortical areas (V1, V2, and ventral posterior area) and in the higher-tier
visual left lateral occipital cortex was presented in mild to moderate POAG
patients compared with controls. Furthermore, reduced CBF of the right areas V2
and ventral posterior area was correlated with cup-to-disc ratio, total ganglion
cell complex thickness, and average retinal nerve fiber layer thickness.
CONCLUSIONS: In conclusion, the complex pathologic progress of POAG includes
abnormal cerebral perfusion within the visual cortex since the mild to moderate
disease stages. The association of cerebral perfusion changes with alterations of
the optic disc and the retina may contribute to the early diagnosis of POAG.
PMID- 29952822
TI - Endophthalmitis Following XEN Stent Exposure.
AB - BACKROUND: XEN45 Gel stents are in their infancy, and clinical expertise with
microsurgical glaucoma devices are increasing. The soft flexible nature of the
XEN stent together with its malleability under the conjunctival tissue should
negate any risk of exposure of the XEN45 stent (XEN). However, we report a case
in which sight-threatening endophthalmitis was the presenting feature of this
complication. CASE REPORT: We present a case of uncomplicated XEN implantation
that developed endophthalmitis 4 months after surgery. She gave an 8-day history
of diarrhea before presentation. She was noted to have exposure of the XEN stent
at the point of entry of the XEN into the subconjunctival space. The stent was
removed, pars plana vitrectomy was carried out, and intravitreal antibiotics were
administered. Achieving low intraocular pressures, bearing in mind her
preservative allergy, became a challenge, as we struggled to manage her advanced
glaucoma medically. A CyPass Micro-Stent was subsequently inserted to control the
intraocular pressure. CONCLUSIONS: Episodes of XEN stent exposure may not be so
isolated. We postulate that poor handwashing transmitted the causative organism
to the exposed stent, which then resulted in endopthalmitis. We would like to
highlight a few learning points from this case.
PMID- 29952823
TI - Evaluation of Pupil Fields Using a Newly Developed Head-mounted Perimeter in
Healthy Subjects.
AB - PURPOSE: The purpose of this study was to evaluate the accuracy of pupil fields
and determine the normative pupillary response data by age using a newly
developed head-mounted perimeter. METHODS: A total of 100 healthy subjects (age,
20 to 68 y) were enrolled. The newly developed head-mounted perimeter "imo" was
used to measure the percentage pupil constriction (PPC) as response to a stimulus
at all 36 test points of the visual field. Goldmann size III and V stimuli at 0,
8, and 11 decibels (dB) under 31.4, 6, and 3 apostilbs (asb) background were
presented. The PPC correlations (r) of the right and left eyes were examined.
Reproducibility was determined with the coefficient of variation (CV) and a Bland
Altman plot. By a simple bootstrap method, the mean PPC were analyzed as
normative data in all 36 test points. RESULTS: Excellent correlation between both
eyes was obtained for Goldmann size V stimuli, target luminance of 0 dB, and a
background luminance of 31.4 asb (r=0.83; P<0.001). From the test-retest CV
peripheral areas have low reproducibility compared with central areas. With a
Goldmann size V target, there was a steeper decline of the PPC from the center
field to the periphery field, and the temporal field PPC was larger than the
nasal field. No major differences were observed between the PPC data and the age
groups by decade (eg, center 3 degrees; P=0.223-0.913). CONCLUSIONS: Normative
PPC data might well be useful for assessing objective visual fields with the
newly developed head-mounted perimeter.
PMID- 29952824
TI - Familial Risks of Glaucoma in the Population of Sweden.
AB - BACKGROUND: Glaucoma has a familial component but detailed data on the
modification of familial risks are lacking. The aim of the study was to determine
detailed familial risks for medically diagnosed glaucoma based on nationwide
hospital and population records. MATERIALS AND METHODS: Subjects were obtained
from the multigeneration register, contains the Swedish population in families,
and glaucoma patients were identified from the hospital discharge register (1987
2012) and the outpatient register (2001-2012). Standardized incidence ratios
(SIRs) were calculated as the ratio of observed to expected number of cases.
RESULTS: Familial risks were increased in both male and female individuals.
Concordant familial risks were generally higher than discordant risks. For
example, familial concordant risks were SIR=3.25 (95% confidence interval, 3.16
3.35) for primary open-angle glaucoma, 9.93 (95% confidence interval, 7.30-13.22)
for primary angle-closure glaucoma. Very high familial risks were observed if >=2
relatives were affected, for example, the high-risk group of multiple affected
siblings with an SIR>20. The spouse risk was modestly increased 1.20. CONCLUSIONS
AND RELEVANCE: Family history of glaucoma is a strong predictor for glaucoma, and
is a potential useful tool in clinical risk assessment. Our data emphasize the
contribution of familial factors to the glaucoma.
PMID- 29952827
TI - Physical Activity and Skipping Breakfast Have Independent Effects on Body Fatness
Among Adolescents.
AB - OBJECTIVE: We analyzed the longitudinal relationship between breakfast intake and
adiposity among adolescents, and the possible mediation role of physical activity
on this phenomenon. METHODS: We conducted the longitudinal study composed of 86
adolescents (11-14 years old), absence of any known chronic diseases and no
regular medicine use that returned the formal consent and assent both signed.
Breakfast intake was reported through face-to-face interviews. Adiposity was
assessed using a densitometry scanner. Physical activity was estimated through
step counts performed using pedometers. Biological maturation was estimated
through the maturity level. Student t test for independent samples was used to
compare adolescents who were "nonskipping breakfast" and "skipping breakfast,"
whereas the relationship between adiposity, physical activity, and skipping
breakfast was assessed using Pearson correlation. Structural equation model was
created to identify the mediation role of physical activity on the relationship
between nonskipping breakfast and adiposity. RESULTS: After 12 months,
adolescents who had consumed breakfast regularly presented decreased trunk
fatness (-3.5% [95% confidence interval (CI): -6.9 to -0.2]) and body fatness (
2.3% [95% CI: -3.9 to -0.7]) compared with their counterparts. Physical activity
had an inverse relationship with trunk fatness (r = -0.270 [95% CI: -0.457 to
0.060]). Nonskipping breakfast was, however, not significantly related to trunk
fatness; however, physical activity seems to reduce trunk fatness in our sample
(r = -0.281; 95% CI: -0.479 to -0.083). CONCLUSIONS: Adolescents who ate
breakfast regularly presented lower body fatness independent of physical
activity, whereas trunk fatness decreased in adolescents who improved physical
activity.
PMID- 29952828
TI - Dehydrated Hereditary Stomatocytosis Presenting as Severe Perinatal Ascites and
Cholestasis.
PMID- 29952830
TI - Variceal Bleeding and Morbidity- Considerations for Primary Prophylaxis.
PMID- 29952829
TI - Polyethylene Glycol Maintenance Treatment for Childhood Functional Constipation:
A Randomized, Placebo-controlled Trial.
AB - OBJECTIVE: The aim of this study was to investigate the long-term efficacy of
polyethylene glycol (PEG) during maintenance treatment of childhood functional
constipation (FC) in a randomized, double-blinded, placebo-controlled trial.
METHODS: Children (2-16 years) with FC according to the Rome III criteria were
randomly assigned to maintenance treatment with PEG or placebo for 24 weeks.
Children reporting treatment failure before 24 weeks were switched to
conventional treatment. Primary outcome was successful treatment, defined as
absence of any Rome III criteria with or without use of medication after 24
weeks. RESULTS: A total of 102 children were included: PEG/placebo: 49/53. At 24
weeks, significantly more patients in the PEG group, compared to the placebo
group, were successfully treated (33 [67%] vs 19 [36%] hazard ratio (95%
confidence intervals) = 3.21 [1.73-5.94]). Significantly fewer children in the
PEG group switched to rescue medication (2 [4%] vs 30 [57%], P < 0.001). Time
before the change to rescue medication was 13 and 27 days, respectively, for each
of the 2 children in the PEG group who required rescue medication. Median time to
shift to rescue medication was 27 days (range: 3-64 days) in the placebo group.
At 24 weeks after initiation of treatment, 33 children (67%) in the PEG group
were successfully treated, compared to 19 children (32%) in the placebo group
(hazard ratio (95% confidence intervals) = 3.21 [1.73-5.94]). No serious adverse
event related to use of the medication was registered. CONCLUSIONS: Maintenance
treatment with PEG is significantly more effective than placebo in preventing
relapse of constipation symptoms during long-term maintenance treatment in
childhood FC. We therefore recommend that maintenance treatment commence after
disimpaction.
PMID- 29952832
TI - Update on amino acid PET of brain tumours.
AB - PURPOSE OF REVIEW: The aim of this study was to give an update on the emerging
role of PET using radiolabelled amino acids in the diagnostic workup and
management of patients with cerebral gliomas and brain metastases. RECENT
FINDINGS: Numerous studies have demonstrated the potential of PET using
radiolabelled amino acids for differential diagnosis of brain tumours,
delineation of tumour extent for treatment planning and biopsy guidance,
differentiation between tumour progression and recurrence versus treatment
related changes, and for monitoring of therapy. The Response Assessment in Neuro
Oncology (RANO) working group - an international effort to develop new
standardized response criteria for clinical trials in brain tumours - has
recently recommended the use of amino acid PET imaging for brain tumour
management in addition to MRI at every stage of disease. With the introduction of
F-18 labelled amino acids, a broader clinical application has become possible,
but is still hampered by the lack of regulatory approval and of reimbursement in
many countries. SUMMARY: PET using radiolabelled amino acids is a rapidly
evolving method that can significantly enhance the diagnostic value of MRI in
brain tumours. Current developments suggest that this imaging technique will
become an indispensable tool in neuro-oncological centres in the near future.
PMID- 29952833
TI - Recent advances in headache neuroimaging.
AB - PURPOSE OF REVIEW: Primary headaches, such as migraine and cluster headache, are
one of the most common and disabling neurological diseases worldwide.
Neuroimaging studies have changed the way we understand these diseases and have
enriched our knowledge of the mechanisms of actions of currently available
therapies. RECENT FINDINGS: The present review highlights the major findings
reported in migraine and cluster headache neuroimaging over the last year.
Widespread structural and functional abnormalities in cortical and subcortical
areas involved in multisensory, including pain, processing have been shown in
migraine and cluster headache patients during different phases of the disease.
Beyond the involvement of single brain areas, dysfunctional brain networks
contribute to their pathophysiology. New central mechanisms of action of headache
preventive treatments have also been explored. SUMMARY: A better understanding of
migraine and cluster headache biology has paved the way for the development of
new improved treatments for both these conditions. Although significant advances
have been made over the last year, there are still many unsolved questions to
address.
PMID- 29952834
TI - MRI in multiple sclerosis: what is changing?
AB - PURPOSE OF REVIEW: To summarize recent findings from the application of MRI in
the diagnostic work-up of patients with suspected multiple sclerosis (MS), and to
review the insights into disease pathophysiology and the utility of MRI for
monitoring treatment response. RECENT FINDINGS: New evidence from the application
of MRI in patients with clinically isolated syndromes has guided the 2017
revision of the McDonald criteria for MS diagnosis, which has simplified their
clinical use while preserving accuracy. Other MRI measures (e.g., cortical
lesions and central vein signs) may improve diagnostic specificity, but their
assessment still needs to be standardized, and their reliability confirmed. Novel
MRI techniques are providing fundamental insights into the pathological
substrates of the disease and are helping to give a better understanding of its
clinical manifestations. Combined clinical-MRI measures of disease activity and
progression, together with the use of clinically relevant MRI measures (e.g.,
brain atrophy) might improve treatment monitoring, but these are still not ready
for the clinical setting. SUMMARY: Advances in MRI technology are improving the
diagnostic work-up and monitoring of MS, even in the earliest phases of the
disease, and are providing MRI measures that are more specific and sensitive to
disease pathological substrates.
PMID- 29952835
TI - MRI-based neuroimaging: atypical parkinsonisms and other movement disorders.
AB - PURPOSE OF REVIEW: MRI has become a well established technical tool for
parkinsonism both in the diagnostic work-up to differentiate between causes and
to serve as a neurobiological marker. This review summarizes current developments
in the advanced MRI-based assessment of brain structure and function in atypical
parkinsonian syndromes and explores their potential in a clinical and
neuroscientific setting. RECENT FINDINGS: Computer-based unbiased quantitative
MRI analyses were demonstrated to guide in the discrimination of parkinsonian
syndromes at single-patient level, with major contributions when combined with
machine-learning techniques/support vector machine classification. These
techniques have shown their potential in tracking the disease progression,
perhaps also as a read-out in clinical trials. The characterization of different
brain compartments at various levels of structural and functional alterations can
be provided by multiparametric MRI, including a growing variety of diffusion
weighted imaging approaches and potentially iron-sensitive and functional MRI.
SUMMARY: In case that the recent advances in the MRI-based assessment of atypical
parkinsonism will lead to standardized protocols for image acquisition and
analysis after the confirmation in large-scale multicenter studies, these
approaches may constitute a great achievement in the (operator-independent)
detection, discrimination and characterization of degenerative parkinsonian
disorders at an individual basis.
PMID- 29952836
TI - Myoclonus-dystonia: classification, phenomenology, pathogenesis, and treatment.
AB - PURPOSE OF REVIEW: The present study will highlight recent advances in the field
of myoclonus-dystonia with a focus on clinical aspects, pathogenesis, and
treatment. We will also discuss genetics, classification issues, and diagnostic
criteria. RECENT FINDINGS: Myoclonus-dystonia is a clinical syndrome
corresponding to the phenotype linked to SGCE, the main causative gene. Childhood
onset myoclonus that predominates over dystonia with prominent upper body
involvement, an absence of truncal dystonia, associated anxiety or compulsivity,
and a positive family history are helpful diagnostic clues. Recent studies
demonstrated that zonisamide is an interesting therapeutic option in myoclonus
dystonia, and that bilateral pallidal stimulation has major and lasting
therapeutic effects. Accumulating evidence suggests that an alteration in
cerebello-thalamic pathway function may play a prominent role and that this is
possibly related to a GABAergic deficit reflecting Purkinje cell dysfunction.
Impaired striatal plasticity and disturbed serotonin homeostasis may also be
implicated. Newly available cellular and rodent models may further assist in
investigating the pathogenesis of this disorder. SUMMARY: Comprehensive analysis
of the phenotype and precise classification are important in patients with
myoclonus and dystonia to identify homogeneous groups of patients. This is
critical to guide tailored therapeutic strategies and promote effective research.
PMID- 29952837
TI - Preparticipation Cardiovascular Screening: An Infrastructure Assessment in
Collegiate Athletics.
AB - OBJECTIVE: To assess the available infrastructure for secondary testing after
preparticipation cardiovascular screening of collegiate athletes. DESIGN: Cross
sectional study. SETTING: National Collegiate Athletic Association (NCAA)
athletic programs PARTICIPANTS:: Team physicians. INTERVENTIONS: Online survey
distributed by the NCAA and American Medical Society for Sports Medicine. MAIN
OUTCOME MEASURES: Availability of secondary cardiovascular diagnostic testing and
services. RESULTS: Team physicians from 235 schools completed the assessment,
representing 21% of all NCAA schools. Ninety (38.3%) NCAA team physicians
reported screening athletes using electrocardiogram (ECG). Division I schools
were more likely than Division II and III schools to perform both screening ECG
(RR, 2.38, P < 0.0001) and echocardiogram (RR, 2.83, P = 0.01). More than 97% of
schools had access to resting echocardiogram, stress ECG/echocardiogram, and
Holter monitoring within 25 miles with no significant variability between
divisions, regions, or size of undergraduate student body. Cardiac magnetic
resonance imaging and electrophysiology studies were available within 25 miles of
more than 80% of schools, and genetics testing was available within 25 miles for
64.8%. CONCLUSIONS: Secondary testing for cardiovascular abnormalities seems to
be readily available for NCAA athletes, regardless of division, region, or school
size.
PMID- 29952838
TI - The PRECISION Survey: Preferences of Physicians Regarding Ultrasound-Guided Intra
Articular Injections.
AB - OBJECTIVE: The objectives of this survey study were to: (1) determine practice
patterns, (2) assess beliefs and attitudes toward ultrasound-guided intra
articular injections (UGIIs), (3) identify barriers to the use of UGII, and (4)
determine any differences in beliefs and attitudes based on age or specialty.
METHODS: A survey was developed using a focus group including physicians who
perform intra-articular injections of the knee, shoulder, and/or hip. After
validation by the focus group, the final survey (28 questions) was e-mailed to
members of the Canadian Academy of Sport and Exercise Medicine (N = 632).
RESULTS: A total of 168 responses were received (26.6%). Nearly half of
respondents rarely/never had access to UGII equipment (48.5%), and over half did
not have adequate training in UGIIs (56.8%-68.8%). About half of respondents
agreed that UGII improves accuracy in knee injections (50.9%); only 35.4% agreed
there was evidence to support UGII over non-ultrasound-guided intra-articular
injections (NGIIs) of the knee. Physicians younger than 50 years were
significantly more likely to use UGII for the knee and hip if they had better
access to equipment (P < 0.0005 for both); they were more likely to use UGII for
the knee if it was less time-consuming (P = 0.001). CONCLUSIONS: The majority of
respondents are not using UGII for the knee or shoulder. Physicians may
overestimate their accuracy in performing NGIIs. The biggest barriers to UGII
were identified as: (1) inadequate training; (2) lack of access to equipment; and
(3) lack of time. Younger physicians seem more open to adopting UGII if barriers
are addressed.
PMID- 29952839
TI - Enhanced External Counterpulsation and Recovery From a Plyometric Exercise Bout.
AB - OBJECTIVE: To analyze the effectiveness of enhanced external counterpulsation
(EECP) on recovery from exercise-induced muscle damage (EIMD). DESIGN: This study
followed a crossover, placebo-controlled, counterbalanced design. PARTICIPANTS:
Ten healthy active subjects (7 male; 27 +/- 4 years). INTERVENTIONS: Participants
performed a plyometric exercise bout (10 sets of 10 jumps interspersed with 1
minute rests) and were then assigned to recover for 30 minutes with either EECP
(cuff pressure = 80 mm Hg) or a Sham intervention (0 mm Hg) immediately after
exercise and at 24 hours after exercise. Two weeks later, they repeated the
protocol with the other recovery intervention. MAIN OUTCOME MEASURES: Muscle
soreness, creatine kinase (CK) activity, jump performance, and tensiomyographic
variables were measured before exercise, and 24 and 48 hours after exercise.
RESULTS: The mean jump height of the plyometric bout did not differ between EECP
and Sham (P > 0.05). Exercise resulted in increased muscle soreness (P < 0.001)
and CK levels (P < 0.001), as well as in impaired jump performance (P < 0.05). No
changes were observed in tensiomyographic variables. No significant differences
were found between interventions for any of the study outcomes. CONCLUSIONS: No
benefits on recovery from EIMD after a plyometric exercise bout were observed
with EECP.
PMID- 29952840
TI - Management of Pain in Elite Athletes: Identified Gaps in Knowledge and Future
Research Directions.
AB - OBJECTIVE: For elite athletes to train and compete at peak performance levels, it
is necessary to manage their pain efficiently and effectively. A recent consensus
meeting on the management of pain in elite athletes concluded that there are many
gaps in the current knowledge and that further information and research is
required. This article presents the crystallization of these acknowledged gaps in
knowledge. DATA SOURCES: Information was gathered from a wide variety of
published scientific sources that were reviewed at the consensus meeting and the
gaps in knowledge identified. MAIN RESULTS: Gaps have been identified in the
epidemiology of analgesic use, the management of pain associated with minor
injuries, and the field of play management of pain for athletes with major
injuries. From a pharmacological perspective, there is a lack of information on
the prescribing of opioid medications in elite athletes and more data are
required on the use of local anesthetics injections, corticosteroids, and
nonsteroidal anti-inflammatory drugs during training and in competition. Pain
management strategies for the general population are widely available, but there
are few for the elite sporting population and virtually none for elite athletes
with a disability. More research is also needed in assessing cognitive-behavior
therapies in improving specific outcomes and also into the new process of
psychologically informed physiotherapy. A key issue is the paucity of data
relating to incidence or prevalence of persistent pain and how this relates to
persistent dysfunction, exercise performance, and physiological function in later
life. CONCLUSIONS: The identification of the gaps in knowledge in the management
of pain in elite athletes will provide a unified direction for the retrieval of
information and further research that will provide reassurance, speed return to
active sport, and benefit performance.
PMID- 29952841
TI - Sway Balance Mobile Application: Reliability, Acclimation, and Baseline
Administration.
AB - OBJECTIVES: To describe historic baseline session administration practices, to
assess the utility of a practice trial (an acclimation trial) before the official
balance session, and to examine the within-session reliability of the Sway
Balance Mobile Application (SBMA). DESIGN: Retrospective observational study.
SETTING: Middle schools, high schools, and colleges across the United States.
PARTICIPANTS: More than 17 000 student-athletes were included in the Sway Medical
database with 7968 individuals meeting this study's inclusion criteria.
INDEPENDENT VARIABLES: The Sway Medical database included the following subject
characteristics for each student-athlete: age, sex, weight, and height. MAIN
OUTCOME MEASURES: Balance assessment score generated by the SBMA. RESULTS:
Variable administration practices with significant differences between baseline
session averages across methods were found. Individuals who performed an
acclimation trial had a significantly higher baseline session average than those
who did not. Within-session reliability estimates were in the low to adequate
range (r = 0.53-0.78), with higher estimates found for 2 consecutive baseline
tests (r = 0.75-0.78). CONCLUSIONS: For maximum clinical utility, a standardized
protocol for postural control baseline acquisition is necessary. Acclimation
trial should be administered before a baseline session to minimize variability,
especially with only 1 to 2 baseline tests. The highest reliability was observed
across 2 consecutive baseline tests within the same baseline session. We suggest
obtaining baseline balance measurements with an acclimation trial followed by a
baseline session with 2 baseline tests. Prospective studies are required for
validation.
PMID- 29952842
TI - Association Between Clinical and Imaging Outcomes After Therapeutic Loading
Exercise in Patients Diagnosed With Achilles or Patellar Tendinopathy at Short-
and Long-Term Follow-up: A Systematic Review.
AB - OBJECTIVE: To determine the association between clinical and imaging outcomes
after therapeutic loading exercise in Achilles tendinopathy (AT) and patellar
tendinopathy (PT) populations at both short- and long-term follow-up. DATA
SOURCES: The PUBMED and EMBASE databases were searched (up to June 2017) to
identify articles that meet the inclusion criteria: (1) patients diagnosed with
AT (insertional or midportion) or PT; (2) rehabilitation based on therapeutic
loading exercise; and (3) assessment of clinical outcomes and tendon structure
using an imaging modality. MAIN RESULTS: Two independent reviewers screened 2894
search results, identifying 21 suitable studies. According to the studies
included in this review, clinical results showed significant improvements for
patients with AT and PT after eccentric exercise (ECC) and heavy slow resistance
(HSR) at short- and long-term follow-up. Imaging outcomes were not consistent.
Moderate-to-strong evidence for patients with AT suggested an association between
clinical outcomes and imaging outcomes (tendon thickness and tendon
neovascularization) after ECC at long-term follow-up. For patients with PT, there
was moderate evidence supporting an association between clinical outcomes
(questionnaire score and pain) and imaging (tendon thickness and tendon
neovascularization) after ECC at short-term follow-up. For both the AT and PT
groups, there was moderate evidence for an association between clinical outcomes
and tendon thickness and neovascularization after HSR exercise. Results related
to the HSR exercise should be interpreted with caution because of the small
number of studies. CONCLUSIONS: Based on the findings of the present review, the
use of imaging outcomes as a complementary examination to the clinical assessment
was confirmed. Overall, an improvement in clinical outcomes seems to be
associated with a reduction in tendon thickness and tendon neovascularization.
Clinicians should be aware that during the interpretation of the imaging
outcomes, factors such as tendinopathy location, exercise modality performed, and
a follow-up period should be considered.
PMID- 29952843
TI - Concussion Rates Differ by Practice Type and Equipment Worn in an Autonomy Five
Collegiate Football Conference.
AB - OBJECTIVE: Evaluate the rate of concussions across Big 12 Conference football
programs based on (1) equipment worn, (2) contact level, (3) preseason practice
versus in-season practice versus games, and (4) mechanism of injury for
concussion. DESIGN: Descriptive epidemiology study. SETTING: Big 12 Conference
football practices and competitions. PATIENTS (OR PARTICIPANTS): Big 12
Conference football teams. ASSESSMENT OF RISK FACTORS: All Big 12 Conference
institutions collected data on practice types, equipment worn, practice and game
participation, and concussions during the fall, preseasons and regular seasons,
from 2013 to 2016. MAIN OUTCOME MEASURES: Injury rates and injury rate ratios
were reported with 95% confidence intervals (CIs). RESULTS: From 2013 to 2016,
there were 375 concussions reported [0.98/1000 athlete exposures (AEs) (95% CI,
0.88-1.08)], an average of approximately 9 concussions per team per year.
Concussion rates were highest in games (5.73/1000 AE), but among practices,
concussion rates were highest in full-pad (1.18/1000 AEs) and live-contact
(1.28/1000 AEs) practices. Concussion rates increased with increasing contact and
equipment worn. Concussion rates were higher in the preseason than in the regular
season, even when stratifying by contact level and equipment worn. CONCLUSIONS:
Practice concussion rates are highest during fully padded and live-contact
practices, supporting limitations on practice contact and equipment worn to
reduce the risk associated with head-impact exposure. Higher concussion rates in
the preseason and during games indicate an effect of play intensity on concussion
risk, and further research is needed to evaluate the direct effect of practice
contact level and equipment guidelines and restrictions on concussion incidence.
PMID- 29952844
TI - RECONSTITUTION OF THE ELLIPSOID ZONE WITH TOCILIZUMAB IN AUTOIMMUNE RETINOPATHY.
AB - PURPOSE: To demonstrate improvement and stabilization of retinal findings,
including recalcitrant cystoid macular edema, in a patient with nonparaneoplastic
autoimmune retinopathy after treatment with tocilizumab, a humanized monoclonal
antibody against soluble and membrane-bound IL-6 receptor. METHODS: Observational
case report. A 46-year-old woman was diagnosed with nonparaneoplastic autoimmune
retinopathy and followed over 4 years on various immunosuppressive medications
with worsening disease and recalcitrant cystoid macular edema. This report
describes the rapid improvement and stabilization of her ocular disease once
tocilizumab was initiated. RESULTS: Tocilizumab, a monoclonal antibody against
the IL-6 receptor, was initiated at a dose of 8 mg/kg every 4 weeks. Cystoid
macular edema was significantly decreased after just two infusions and nearly
resolved after five infusions. Ellipsoid zone and outer retinal integrity also
improved on optical coherence tomography. The patient tolerated the medication
with limited side effects. CONCLUSION: Long-term immunosuppression is the
cornerstone of treatment for nonparaneoplastic autoimmune retinopathy, although
success is highly variable. We report a case treated with tocilizumab with
dramatic improvement in refractory macular edema and reconstitution of the
ellipsoid zone on optical coherence tomography in a patient with
nonparaneoplastic autoimmune retinopathy. This case highlights the potential role
of treatment with an IL-6 inhibitor in autoimmune retinopathy though further
studies are needed.
PMID- 29952845
TI - The matter of reverse ventricular remodeling after acute myocardial infarction
between fiction and reality.
PMID- 29952846
TI - A new educational program in heart failure drug development: the Brescia
international master program.
AB - : Despite recent advances in chronic heart failure treatment, prognosis of acute
heart failure patients remains poor with a heart failure rehospitalization rate
or death reaching approximately 25% during the first 6 months after discharge. In
addition, about half of these patients have preserved ejection fraction for which
there are no evidence-based therapies. Disappointing results from heart failure
clinical trials over the past 20 years emphasize the need for developing novel
approaches and pathways for testing new heart failure drugs and devices. Indeed,
many trials are being conducted without matching the mechanism and action of the
drug with the clinical event. The implementation of these novel approaches should
be coupled with the training of a new generation of heart failure physicians and
scientists in the art and science of clinical trials. Currently, drug development
is led by opinion leaders and experts who, despite their huge personal
experience, were never trained systematically on drug development. The aim of
this article is to propose a training program of 'drug development in Heart
Failure'. A physician attending this course would have to be trained with a major
emphasis on heart failure pathophysiology to better match mechanisms of death and
rehospitalization with mechanism of action of the drug. Applicants will have to
prove their qualifications and special interest in heart failure drug development
before enrollment. This article should serve as a roadmap on how to apply
emerging general principles in an innovative drug-development-in-heart-failure
process as well as the introduction of a new educational and mentorship program
focusing on younger generations of researchers.
PMID- 29952847
TI - Predictors of left ventricular reverse remodeling in patients with chronic heart
failure.
PMID- 29952848
TI - Highlights of the August issue.
PMID- 29952849
TI - Three-dimensional echocardiography: a further step in the evaluation of
hypertensive heart disease.
PMID- 29952850
TI - The aerobic exercise training in hypertension: a matter of baking ingredients.
PMID- 29952851
TI - Has the time come for self-management of blood pressure and antihypertensive
medications by patients?
PMID- 29952852
TI - Long-term yogurt consumption and risk of incident hypertension in adults.
AB - OBJECTIVE: To evaluate the relation between yogurt consumption as well as cheese,
milk, and total dairy, and high blood pressure (HBP) in two Nurses' Health Study
cohorts (NHS, n = 69 298), NHS II (n = 84 368) and the Health Professionals
Follow-Up Study (HPFS, n = 30 512). METHODS: NHS, NHS II, and HPFS participants
were followed for incident HBP for up to 30, 20, and 24 years, respectively.
Hazard ratios were calculated using time-dependent multivariate-adjusted Cox
proportional hazards models. Pooled risk estimates were derived from fixed
effects meta-analyses. RESULTS: Participants consuming at least five servings per
week (vs. <1 serving per month) of yogurt in NHS, NHS II, and HPFS had 19% (95%
CI 0.75-0.87), 17% (95% CI 0.77-0.90), and 6% (95% CI 0.83-1.07) lower HBP risks,
respectively. In pooled analyses of these cohorts, higher yogurt consumption was
linked with 16% (95% CI 0.80-0.88) lower HBP risk; higher total dairy (3 to <6
vs. <0.5 servings/day), milk (2 to <6/day vs. <4/week) and cheese (1 to 4/day vs.
<1/week) were associated with 16% (95% CI 0.81-0.87), 12% (95% CI 0.86-0.90), and
6% (95% CI 0.90-0.97) lower HBP risks, respectively. After controlling for BMI as
a possible causal intermediate, total dairy, yogurt, milk, and cheese were
associated with 13, 10, 8, and 8% lower HBP risks, respectively. The combination
of higher yogurt intake and higher DASH ('Dietary Approaches to Stop
Hypertension') diet scores was associated with 30% (95% CI 0.66-0.75) lower HBP
risk compared with lower levels of both factors. CONCLUSION: Higher total dairy
intake, especially in the form of yogurt, was associated with lower risk of
incident HBP in middle-aged and older adult men and women.
PMID- 29952853
TI - Cardiac function in pregnancy.
PMID- 29952854
TI - Reply.
PMID- 29952855
TI - A 10-year history of secondary hypertension: a challenging case of renin
secreting juxtaglomerular cell tumor.
PMID- 29952856
TI - Comparative Effectiveness and Safety of Radiofrequency Ablation Versus Argon
Plasma Coagulation for Treatment of Gastric Antral Vascular Ectasia: A Systematic
Review and Meta-Analysis.
AB - BACKGROUND AND AIMS: Although argon plasma coagulation (APC) is the current
standard endoscopic treatment for gastric antral vascular ectasia (GAVE),
radiofrequency ablation (RFA) has emerged as an attractive alternative. The aim
of this study was to perform a systematic review and meta-analysis to evaluate
the comparative effectiveness and safety of RFA and APC in the treatment of GAVE.
MATERIALS AND METHODS: Searches of PubMed, EMBASE, Web of Science, and Cochrane
Library databases along with major gastroenterology annual meetings were
performed through March 2017. Measured outcomes for comparative effectiveness and
safety including improvement in hemoglobin levels, transfusion dependence, number
of treatment sessions, complications, follow-up, and author-reported endoscopic
success were compared among RFA and APC studies. RESULTS: In total, 24 studies
(n=508) involving APC and 9 studies (n=104) on RFA were included. Mean age of
patients included was comparable in both groups (65.33+/-7.80 y for APC vs.
66.96+/-6.23 y for RFA; P=0.98). Pooled mean follow-up was significantly longer
for APC compared with RFA (19.52+/-13.11 vs. 7.43+/-3.72 mo; P<0.001). In total,
47% of RFA patients were refractory to previous treatment with APC. RFA required
fewer mean treatment sessions compared with APC (2.10 vs. 3.39, respectively;
P<0.001). RFA resulted in fewer and less severe complications as compared with
APC (1.92% vs. 5.12%, respectively; P<0.001). Although the reported endoscopic
success was better with RFA compared with APC (97% vs. 66%; P<0.001), the
posttreatment pooled hemoglobin increase and reduction in transfusion dependence
was higher for APC compared with RFA [weighted mean difference 3.10 g/dL (95%
confidence interval, 2.92-3.28) vs. 1.95 g/dL (95% confidence interval, 1.62
2.26); P<0.001; and 88% vs. 66%; P<0.001, for APC and RFA, respectively].
CONCLUSIONS: There is limited long-term data on RFA for GAVE; however, available
evidence suggests RFA has a comparable efficacy and tolerability compared with
APC. In addition, RFA seems to be effective for APC-refractory GAVE patients.
Future controlled trials are needed to directly compare treatment efficacy, long
term durability, safety, and cost-effectiveness between these interventions.
PMID- 29952857
TI - Sorafenib for Treatment of Hepatocellular Carcinoma: A Survival Analysis From the
South American Liver Research Network.
AB - GOALS: We aim to describe the efficacy, safety profile, and variables associated
with survival in patients with hepatocellular carcinoma (HCC) treated with
sorafenib in South America. BACKGROUND: Sorafenib has been shown to improve
survival in patients with advanced HCC. There are few data on sorafenib use for
HCC in South America. STUDY: We performed a retrospective analysis of HCC cases
treated with sorafenib from 8 medical centers in 5 South American countries,
between January 2010 and June 2017. The primary endpoint was overall survival
(OS), which was defined as time from sorafenib initiation to death or last follow
up. Risk factors for decreased OS were assessed using Cox proportional hazard
regression and log-rank tests. RESULTS: Of 1336 evaluated patients, 127 were
treated with sorafenib and were included in the study. The median age of
individuals was 65 years (interquartile range, 55 to 71) and 70% were male
individuals. Median OS in all patients was 8 months (interquartile range, 2 to
17). Variables associated with survival on multivariate analysis were platelets
>/<250,000 mm (2 vs. 8 mo, P=0.01) and Barcelona Clinic Liver Cancer (BCLC) stage
(A/B, 13 vs. C/D, 6 mo; P=0.04). In a subanalysis of patients with BCLC stage C,
platelets >/<250,000 mm were also independently associated with survival (2 vs.
5.5 mo, P=0.03). Patients lived longer if they experienced any side effects from
sorafenib use (11 vs. 2 mo, P=0.009). Patients who stopped sorafenib because of
side effects had shorter survival compared with patients who were able to
tolerate side effects and continue treatment (7.5 vs. 13 mo, P=0.01).
CONCLUSIONS: Pretreatment elevation of platelets and advanced BCLC stage were
independently associated with poor survival on sorafenib in a South American
cohort.
PMID- 29952858
TI - Safety of Transcranial Magnetic Stimulation in an Obsessive-Compulsive Disorder
Patient With Deep Brain Stimulation: A Case Report.
PMID- 29952859
TI - The Successful Use of Electroconvulsive Therapy in a Patient With Cerebral
Aneurysms and a Pituitary Lesion.
PMID- 29952861
TI - Successful Treatment With Electroconvulsive Therapy of a Patient With Chiari
Malformation Type I.
PMID- 29952862
TI - Effectiveness and Cognitive Changes With Ultrabrief Right Unilateral and Other
Forms of Electroconvulsive Therapy in the Treatment of Mania.
AB - OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment in mania.
However, there is little evidence regarding the use of ultrabrief right
unilateral (RUL-UB) ECT in treatment of acute manic episodes. The aim of this
study was to report on the effectiveness and cognitive profile of ECT in bipolar
mania, including a sample who received RUL-UB ECT. METHODS: This naturalistic
study retrospectively collected data in 33 patients who received ECT with
concurrent antipsychotics for mania between October 1, 2014, and July 30, 2016.
Electroconvulsive therapy was given using RUL-UB, brief-pulse right unilateral,
or brief-pulse bitemporal approaches, dosed according to the patient's seizure
threshold. The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale
(YMRS) score, and the Montreal Cognitive Assessment (MoCA) were administered to
patients before and after the ECT course. RESULTS: For the whole sample, there
was a significant improvement in BPRS (total score and manic subscale), YMRS, and
MoCA total scores across the ECT treatment course. The overall BPRS response rate
was 84%, and mean scores decreased from 42.1 (SD, 12.0) to 26.0 (SD, 4.0). The 13
patients who received RUL-UB ECT also showed significant improvement in BPRS,
YMRS, and MoCA scores over the treatment course. CONCLUSIONS: Electroconvulsive
therapy in general and also specifically RUL-UB ECT were effective in treating
mania and also led to global cognitive improvement.
PMID- 29952863
TI - Exposure Therapy and Simultaneous Repetitive Transcranial Magnetic Stimulation: A
Controlled Pilot Trial for the Treatment of Posttraumatic Stress Disorder.
AB - OBJECTIVES: This is a small preliminary but novel study assessing the feasibility
of repetitive transcranial magnetic stimulation (rTMS) delivery to veterans with
posttraumatic stress disorder (PTSD) while they simultaneously receive prolonged
exposure (PE) therapy. METHODS: A prospective, randomized, double-blinded, active
sham-controlled design combined weekly sessions of rTMS and standard PE at the
Veterans Administration Hospital. Eight adult patients received a full course of
protocol-driven PE therapy and were randomly assigned to receive either rTMS or
sham rTMS. Repetitive transcranial magnetic stimulation was delivered to the
right or left prefrontal cortex with a figure-eight solid core coil at 120% motor
threshold, 10 Hz, 5-second train duration, and 10-second intertrain interval for
30 minutes (6000 pulses) weekly for 5 weeks (30,000 stimuli). RESULTS: Of the 12
veterans consented, 8 completed the study treatment protocol. The dropout rate
was 34%, roughly equivalent to the pooled average dropout rates observed in
traditional PE therapy with Operation Enduring Freedom/Operation Iraqi Freedom
veterans with PTSD, suggesting that veterans had no difficulty tolerating the
addition of rTMS to PE therapy and that this is a feasible study design for
larger trials in the future. Clinician-Administered PTSD Symptom scores reflected
a general nonsignificant trend toward improvement, and subjects with comorbid
major depression appeared to experience significant antidepressant benefit with
treatment despite the fact that the doses used in this protocol were much smaller
than those used to treat patients with major depressive disorder. CONCLUSIONS:
This pilot study demonstrates the safety and feasibility of rTMS delivery to PTSD
patients while they simultaneously receive PE. This unique approach to the
treatment of PTSD highlights the need for further studies with larger sample
sizes to assess treatment outcomes.
PMID- 29952860
TI - Transcranial Direct Current Stimulation as a Therapeutic Tool for Chronic Pain.
AB - Transcranial direct current stimulation (tDCS) modulates spontaneous neuronal
activity that can generate long-term neuroplastic changes. It has been used in
numerous therapeutic trials showing significant clinical effects especially when
combined with other behavioral therapies. One area of intensive tDCS research is
chronic pain. Since the initial tDCS trials for chronic pain treatment using
current parameters of stimulation, more than 60 clinical trials have been
published testing its effects in different pain syndromes. However, as the field
moves in the direction of clinical application, several aspects need to be taken
into consideration regarding tDCS effectiveness and parameters of stimulation. In
this article, we reviewed the evidence of tDCS effects for the treatment of
chronic pain and critically analyzed the literature pertaining its safety and
efficacy, and how to optimize tDCS clinical effects in a therapeutic setting. We
discuss optimization of tDCS effects in 3 different domains: (i) parameters of
stimulation, (ii) combination therapies, and (iii) subject selection. This
article aims to provide insights for the development of future tDCS clinical
trials.
PMID- 29952864
TI - Efficiency of Pneumatic Tourniquet Cuff With Asymmetric Pressure Distribution at
Rest and During Isometric Muscle Action.
AB - Ipavec, M, Grapar Zargi, T, Jelenc, J, and Kacin, A. Efficiency of pneumatic
tourniquet cuff with asymmetric pressure distribution at rest and during
isometric muscle action. J Strength Cond Res XX(X): 000-000, 2018-The aim of this
study was to compare effects of newly designed double-chamber cuff with
asymmetric pressure (APC) distribution and standard single-chamber cuff with
symmetric pressure (SPC) distribution on muscle perfusion and volitional
activation. First, the 2 cuffs were compared bilaterally on resting thigh muscles
of 17 healthy volunteers at 4 cuff pressures (120, 160, 200, and 240 mm Hg).
Then, the subjects performed the isometric endurance test of knee extensor
muscles to volitional failure at 40% of maximal volitional isometric action in
both free-flow and blood flow restricted condition. Changes in hemoglobin
kinetics in vastus lateralis muscle (near-infrared spectroscopy), surface
electromyography of vastus medialis muscle, and pain intensity (visual analogue
scale [VAS]) were continuously recorded. At rest, a significant difference (p =
0.009) in velocity of change in total hemoglobin concentration was noted between
the cuffs at 160 mm Hg (APC = 0.028 MUM.s and SPC = 0.056 MUM.s). The VAS scores
significantly increased (p = 0.031) at pressures >=200 mm Hg, with no difference
between the cuffs. Duration of isometric action with blood flow restriction was
12% shorter (p = 0.003) than in free-flow condition, with no difference between
the cuffs. There were no significant differences in muscle activation or
hemoglobin kinetics between the exercise conditions or cuff types. The results
show that APC reduces blood flow in quadriceps femoris muscle at rest at lower
pressure than SPC, which suggests its enhanced efficiency for blood flow
restriction. Given that application of either type of cuff during sustained
isometric action had only minor impact on muscle endurance and oxygen kinetics,
future research must focus primarily on dynamic muscle actions.
PMID- 29952865
TI - Kinematic Comparison of the Roundhouse Kick Between Taekwondo, Karate, and
Muaythai.
AB - Diniz, R, Del Vecchio, FB, Schaun, GZ, Oliveira, HB, Portella, EG, da Silva, ES,
Formalioni, A, Campelo, PCC, Peyre-Tartaruga, LA, and Pinto, SS. Kinematic
comparison of the roundhouse kick between taekwondo, karate, and muaythai. J
Strength Cond Res XX(X): 000-000, 2018-The roundhouse kick (RHK) is frequently
executed in taekwondo, karate, and muaythai because of its high technical
effectiveness during combat. The purpose of this study was to compare kinematic
characteristics during RHK performance between taekwondo, karate, and muaythai
athletes. Forty-seven male athletes (25.5 +/- 4.7 years, 1.75 +/- 0.1 m, and 75.8
+/- 11.5 kg) volunteered to participate (taekwondo: 17; karate: 15; and muaythai:
15). Self-selected distance from target, mean and peak fifth metatarsus linear
velocity (LV5mean; LV5peak), mean and peak hip (HAVmean; HAVpeak) and knee
(KAVmean; KAVpeak) angular velocities, as well as target linear acceleration
(TLA) were analyzed with a 3D video motion analysis system. Comparisons between
modalities were performed with 1-way analysis of variances and Bonferroni's post
hoc test (alpha = 0.05). Self-selected distance was lower in muaythai compared
with taekwondo and karate (p < 0.001). Also, karate had greater LV5mean compared
with muaythai (p = 0.001), and muaythai showed higher HAVmean than karate (p =
0.011). In addition, HAVpeak was greater in muaythai than in taekwondo and karate
(p < 0.001). No differences were found for KAVmean, KAVpeak, and TLA. Although it
is similarly described between modalities, RHK showed distinct kinematic
characteristics between taekwondo, karate, and muaythai. Based on these results,
coaches and athletes can improve their RHK technique according to the
specificities of each combat sport. Specifically, it is suggested that combat
strategies should aim to increase the distance from the opponent during combat
for muaythai athletes, whereas taekwondo and karate athletes should focus on
decreasing it.
PMID- 29952866
TI - Immune Response Related With Skin Thermal Pattern in Judokas: A New Application
for Infrared Thermography?
AB - Brito, CJ, Moreira, DG, Ferreira, JJ, Diaz-de-Durana, AL, Miarka, B, Bouzas
Marins, JC, and Sillero-Quintana, M. Immune response related with skin thermal
pattern in judokas: A new application for infrared thermography? J Strength Cond
Res XX(X): 000-000, 2018-This study investigated the association between body
skin temperature (BST) and immune response after judo training, and compared the
immune responses considering 2 post-training skin thermal pattern ("spots"-SPT
and "localized"-LOC). For this, we evaluated 32 (25-male) black-belt judokas from
the Spanish Junior National Team (18.0 +/- 3.5 years, 72.4 +/- 18.4 kg, and 17.1
+/- 7.5% body fat). White blood cell and BST measurements were performed at pre
training, immediately, 1, and 24-hour post-training. Body skin temperature (
degrees C) was estimated by skin temperature from 4 regions of interest (chest,
upper arm, thigh, and calf). The main results indicated that 13 judokas were
classified as SPT and 19 as LOC. In comparison with LOC, SPT had a significantly
lower BST post-training (SPT = 33.0 +/- 0.4 vs. LOC = 33.6 +/- 0.8 degrees C; p
= 0.016), lower blood concentration of leukocytes (SPT = 7.9 +/- 1.9 vs. LOC =
8.9 +/- 1.9 cells * 10 per mm; p <= 0.001), and neutrophils (SPT = 5.5 +/- 1.7
vs. LOC = 6.1 +/- 2.2 cells * 10 per mm; p <= 0.001). In conclusion, the BST and
immune response after judo training seem to be not associated. However, when the
skin thermal pattern is considered, the SPT skin thermal pattern presented a
lower post-training BST, blood leukocytes, and neutrophils in comparison with the
LOC group. These results show a possible relationship between skin thermal
pattern and immune responses for the first time; however, further studies are
needed to confirm the evidence presented here.
PMID- 29952867
TI - Does Intra-abdominal Pressure Have a Causal Effect on Muscle Strength of Hip and
Knee Joints?
AB - Tayashiki, K, Kanehisa, H, and Miyamoto, N. Does intra-abdominal pressure have a
causal effect on muscle strength of hip and knee joints? J Strength Cond Res
XX(X): 000-000, 2018-It remains unclear whether intra-abdominal pressure (IAP)
has a causal effect on lower-limb muscle strength. This study aimed to clarify
whether or not changes in IAP, induced by changing breathing state, influence
muscle strength of hip and knee extensor and flexor. Eighteen healthy males (age:
22.0 +/- 2.2 years, height: 1.71 +/- 0.03 m, and body mass: 68.1 +/- 6.1 kg)
performed maximal voluntary isometric contractions (MVICs) of hip and knee
extensor and flexor during breath-hold at full inspiration (inspiratory
condition) or expiration (expiratory condition), or during normal breath-hold
(normal condition). Intra-abdominal pressure was obtained by a pressure
transducer placed in the rectum and determined at the time at which the developed
torque reached to the maximum. The IAP during each MVIC was significantly greater
in inspiratory condition than in expiratory condition (p < 0.05). The maximal
torque of hip extensor was significantly greater in inspiratory condition than in
expiratory condition (p < 0.05). By contrast, the maximal torque of each of hip
flexor, knee extensor, and knee flexor was not different among the 3 breath-hold
conditions. The IAP was significantly correlated with the maximal torque of hip
extensor in each breath-hold condition. The current results suggest that a
sufficient increase in IAP has a causal effect to specifically improve muscle
strength of hip extensor.
PMID- 29952868
TI - Test-Retest Reliability of a Commercial Linear Position Transducer (GymAware
PowerTool) to Measure Velocity and Power in the Back Squat and Bench Press.
AB - Orange, ST, Metcalfe, JW, Marshall, P, Vince, RV, Madden, LA, and Liefeith, A.
Test-retest reliability of a commercial linear position transducer (GymAware
PowerTool) to measure velocity and power in the back squat and bench press. J
Strength Cond Res XX(X): 000-000, 2018-This study examined the test-retest
reliability of the GymAware PowerTool (GYM) to measure velocity and power in the
free-weight back squat and bench press. Twenty-nine academy rugby league players
(age: 17.6 +/- 1.0 years; body mass: 87.3 +/- 20.8 kg) completed 2 test-retest
sessions for the back squat followed by 2 test-retest sessions for the bench
press. GYM measured mean velocity (MV), peak velocity (PV), mean power (MP), and
peak power at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM). GYM showed
good reliability (intraclass correlation coefficient [ICC] and standard error of
measurement percentage, respectively) for the measurement of MV at loads of 40
(0.77, 3.9%), 60 (0.83, 4.8%), 80 (0.83, 5.8%), and 90% (0.79, 7.9%) of 1RM in
the back squat. In the bench press, good reliability was evident for PV at 40
(0.82, 3.9%), 60 (0.81, 5.1%), and 80% (0.77, 8.4%) of 1RM, and for MV at 80
(0.78, 7.9%) and 90% (0.87, 9.9%) of 1RM. The measurement of MP showed good to
excellent levels of reliability across all relative loads (ICC >=0.75). In
conclusion, GYM provides practitioners with reliable kinematic information in the
back squat and bench press, at least with loads of 40-90% of 1RM. This suggests
that strength and conditioning coaches can use the velocity data to regulate
training load according to daily readiness and target specific components of the
force-velocity curve. However, caution should be taken when measuring movement
velocity at loads <40% of 1RM.
PMID- 29952869
TI - Physiological Adaptations to High-Intensity Interval and Continuous Training in
Kayak Athletes.
AB - Papandreou, A, Philippou, A, Zacharogiannis, E, and Maridaki, M. Physiological
adaptations to high-intensity interval and continuous training in kayak athletes.
J Strength Cond Res XX(X): 000-000, 2018-High-intensity interval training (HIIT)
seems to be more effective than continuous training (CT) for the improvement of
physical condition and sports performance. This study compared physiological
adaptations with HIIT and CT in flat water kayak athletes. Twenty-four national
class kayakists were divided into 3 groups (n = 8 per group), 2 of which
participated in an 8-week CT or HIIT program, whereas the third one served as
control (C). An incremental maximum oxygen uptake (V[Combining Dot Above]O2max),
a maximal anaerobic Wingate-type, as well as 1,000-m (T1,000 m) and 200-m (T200
m) time test were performed before and after the training period on a kayak
ergometer, to determine changes in V[Combining Dot Above]O2max, peak blood
lactate ([La]peak), paddling speed at V[Combining Dot Above]O2max (PSVO2max),
heart rate at V[Combining Dot Above]O2max (HRpeak), paddling economy speed (PEs;
speed at 75% of V[Combining Dot Above]O2max), paddling speed at anaerobic
ventilatory threshold (PSVT2), maximal paddling speed (PSpeak), and reduction of
PSpeak (PSR). V[Combining Dot Above]O2max, [La]peak, HRpeak, and PSR did not
change after the 8-week training compared with baseline in either training group
(p > 0.05). However, significant changes were found in PSVT2 and T200 m (HIIT),
PSVO2max, PEs, PSpeak, and T1,000 m (CT and HIIT) (p < 0.05-0.0001) as compared
to baseline. Moreover, percent changes were different between the training groups
in PEs, and between control and training groups in PSpeak and PSVO2peak (p < 0.05
0.01). Both training programs improved physiological and performance variables;
however, HIIT resulted in significant changes of PSVT2 and T200 m and higher
improvement of PEs with 15 times less training time compared with CT. Thus, HIIT
seems more time-efficient than CT for improving paddling economy of kayaking
performance.
PMID- 29952870
TI - U.S. Army Physical Demands Study: Differences in Physical Fitness and
Occupational Task Performance Between Trainees and Active Duty Soldiers.
AB - Canino, MC, Foulis, SA, Zambraski, EJ, Cohen, BS, Redmond, JE, Hauret, KG,
Frykman, PN, and Sharp, MA. U.S. Army Physical Demands Study: Differences in
physical fitness and occupational task performance between trainees and active
duty soldiers. J Strength Cond Res XX(X): 000-000, 2018-U.S. Army initial entry
training (IET) is designed to prepare trainees for the military environment and
subsequent training, including specific programs to increase physical fitness to
perform job-specific tasks to the minimal acceptable performance standard (MAPS).
The aim of this study was to compare physical fitness and occupational task
performance of trainees at the end of IET to that of active duty soldiers. One
hundred seventy-nine male combat arms trainees at the end of IET and 337 male
combat arms active duty soldiers performed a sandbag carry (SBC), casualty drag
(CD), and move under direct fire (MUF). Physical fitness was assessed using Army
Physical Fitness Test scores. A questionnaire was administered to determine
frequency of task performance. Active duty soldiers compared with trainees were
older (p < 0.01) and performed more push-ups (p < 0.01) and sit-ups (p < 0.01).
Trainees performed the 2-mile run faster (p < 0.01). Ninety-four percent of
trainees and 99% of active duty soldiers performed the 3 tasks to the MAPSs.
Active duty soldiers performed significantly faster on both the SBC (p < 0.01)
and CD (p < 0.01) and reported a higher task frequency on the SBC (p = 0.03) and
CD (p < 0.01). No difference in MUF performance (p = 0.16) and task frequency (p
= 0.13) was detected. Initial entry training seems to provide sufficient physical
training as most trainees were able to meet the MAPSs; however, performance
differences were still apparent between trainees and active duty soldiers.
Additional practice performing the physically demanding tasks may help maximize
performance on the physically demanding job requirements.
PMID- 29952871
TI - Shorter Ground Contact Time and Better Running Economy: Evidence From Female
Kenyan Runners.
AB - Mooses, M, Haile, DW, Ojiambo, R, Sang, M, Mooses, K, Lane, AR, and Hackney, AC.
Shorter ground contact time and better running economy: evidence from female
Kenyan runners. J Strength Cond Res XX(X): 000-000, 2018-Previously, it has been
concluded that the improvement in running economy (RE) might be considered as a
key to the continued improvement in performance when no further increase in
V[Combining Dot Above]O2max is observed. To date, RE has been extensively studied
among male East African distance runners. By contrast, there is a paucity of data
on the RE of female East African runners. A total of 10 female Kenyan runners
performed 3 * 1,600-m steady-state run trials on a flat outdoor clay track (400-m
lap) at the intensities that corresponded to their everyday training intensities
for easy, moderate, and fast running. Running economy together with gait
characteristics was determined. Participants showed moderate to very good RE at
the first (202 +/- 26 ml.kg.km) and second (188 +/- 12 ml.kg.km) run trials,
respectively. Correlation analysis revealed significant relationship between
ground contact time (GCT) and RE at the second run (r = 0.782; p = 0.022), which
represented the intensity of anaerobic threshold. This study is the first to
report the RE and gait characteristics of East African female athletes measured
under everyday training settings. We provided the evidence that GCT is associated
with the superior RE of the female Kenyan runners.
PMID- 29952872
TI - Acute and Delayed Effects of a Resistance Training Session Leading to Muscular
Failure on Mechanical, Metabolic, and Perceptual Responses.
AB - Parraga-Montilla, JA, Garcia-Ramos, A, Castano-Zambudio, A, Capelo-Ramirez, F,
Gonzalez-Hernandez, JM, Cordero-Rodriguez, Y, and Jimenez-Reyes, P. Acute and
delayed effects of a resistance training session leading to muscular failure on
mechanical, metabolic, and perceptual responses. J Strength Cond Res XX(X): 000
000, 2018-This study explored the acute and delayed (24 and 48 hours after
exercise) effects of a resistance training session leading to muscular failure.
Eleven resistance-trained men completed a training session consisting on 3 sets
of repetitions to failure during the back-squat exercise performed at the maximum
possible speed with a load equivalent to a mean propulsive velocity (MPV) of 1
m.s (~60% of 1 repetition maximum). A number of mechanical (number of repetitions
and starting MPV of the set, MPV achieved against the 1MPV load, countermovement
jump [CMJ] height, and handgrip strength), metabolic (lactate, uric acid, and
ammonia concentrations), and perceptual (OMNI-RES perceived exertion) variables
were measured. The results revealed (a) a decrease of 38.7% in set 2 and 54.7% in
set 3 of the number of repetitions performed compared with the first set (p <
0.05), (b) a reduction in the MPV of the repetitions and an increase in lactate
concentration and OMNI-RES values with the succession of sets (p < 0.05), (c)
comparable decrements in CMJ height after the 3 sets (25-32%), (d) a decrease in
CMJ height (p < 0.05; 6.7-7.9%) and in the MPV attained against the 1MPV load (p
< 0.05; 13-14%) after 24 and 48 hours of completing the training session, but no
significant changes were observed in handgrip strength (p > 0.05; <2%), and (e)
uric acid and ammonia concentrations above the basal levels (p < 0.05). The large
decrements in mechanical performance together with the high metabolic stress
discourage the frequent use of resistance training sessions leading to muscular
failure.
PMID- 29952873
TI - Running Demands and Activity Profile of the New Four-Quarter Match Format in
Men's Field Hockey.
AB - Ihsan, M, Yeo, V, Tan, F, Joseph, R, Lee, M, and Aziz, AR. Running demands and
activity profile of the new four-quarter match format in men's field hockey. J
Strength Cond Res XX(X): 000-000, 2018-This study determined the running demands
of men's field hockey with regards to the revised four-quarter match format.
Twenty-eight male field hockey players were equipped with global positioning
system units while competing in 14 competitive international games over a 1-year
period. All matches allowed for unlimited substitutions, and consisted of four 15
minute quarters (i.e., Q1-Q4). A progressive decline in total distance (TD) was
observed in Q2 (2,072 +/- 141 m) to Q4 (2,055 +/- 212 m) compared with Q1 (2,171
+/- 195 m, p < 0.05). However, the decline in TD was due to decreases in low
intensity activity (<15 km.h, p < 0.05), as high-intensity running (HIR; >15
km.h) distances were similar throughout Q1-Q4 (p = 0.263). Positional data
demonstrated a similar profile, where significant decreases in TD, but not in
HIR, was observed across all playing positions at some point over the 4 quarters
(p < 0.05). DEF accumulated the lowest amount of TD (7,631 +/- 753 m), HIR (2,257
+/- 498 m), and high-intensity decelerations (60 +/- 9, >-2m.s) compared with MID
and FWD (p < 0.05). By contrast, FWD performed the highest amount of HIR (3,090
+/- 565 m) and high-intensity accelerations (110 +/- 9, >2 m.s) compared with MID
and DEF (p < 0.05). In conclusion, our results showed that although there was a
progressive decline in TD over the 4 quarters of match play, high-intensity
running performance (i.e., HIR and high-intensity acceleration) was maintained
throughout the match regardless of playing position.
PMID- 29952874
TI - The Efficacy of the Lactate Threshold: A Sex-Based Comparison.
AB - Hoffmann, SM, Skinner, TL, van Rosendal, SP, Osborne, MA, Emmerton, LM, and
Jenkins, DG. The efficacy of the lactate threshold: A sex-based comparison. J
Strength Cond Res XX(X): 000-000, 2018-The second lactate threshold (LT2) has
previously been associated with endurance performance; however, comparisons
between sexes are lacking regarding its efficacy. The aim of this study was to
compare LT2 between men and women, specifically regarding its (a) relationship
with endurance performance and (b) capacity to establish training and competition
intensities. Competitive male (mean +/- SD: age, 27.7 +/- 4.7 years; V[Combining
Dot Above]O2max, 59.7 +/- 5.2 ml.kg.min; n = 10) and female (mean +/- SD: age,
27.3 +/- 6.2 years; V[Combining Dot Above]O2max, 54.5 +/- 5.3 ml.kg.min; n = 12)
cyclists and triathletes completed an incremental cycle trial to volitional
fatigue (for determination of V[Combining Dot Above]O2max and LT2 via the
modified D-max method), a constant load (+/-5%) exercise trial of 30 minutes at
LT2 power output, and a 40-km cycle time trial. The LT2 significantly correlated
with 40-km cycling performance in both men (r = -0.69 to -0.77; p < 0.01-0.05)
and women (r = -0.63 to -0.75; p < 0.01-0.05). All men sustained LT2 power output
for 30 minutes, compared with 82% of women. Despite LT2 reflecting a similar
heart rate, V[Combining Dot Above]O2, and [La] to those elicited during a 40-km
time trial in both men and women, power output at LT2 was 6% higher (p < 0.05)
than mean time trial power output in women, with no significant difference in
men. Based on these findings, sex-specific recommendations have been suggested in
regard to the use of LT2 for establishing performance potential, prescribing
endurance training intensities and setting 40-km performance intensity.
PMID- 29952875
TI - Effects of Probiotic (Bacillus subtilis) Supplementation During Offseason
Resistance Training in Female Division I Athletes.
AB - Toohey, JC, Townsend, JR, Johnson, SB, Toy, AM, Vantrease, WC, Bender, D, Crimi,
CC, Stowers, KL, Ruiz, MD, VanDusseldorp, TA, Feito, Y, and Mangine, GT. Effects
of probiotic (Bacillus subtilis) supplementation during offseason resistance
training in female Division I athletes. J Strength Cond Res XX(X): 000-000, 2018
We examined the effects of probiotic (Bacillus subtilis) supplementation during
offseason training in collegiate athletes. Twenty-three Division I female
athletes (19.6 +/- 1.0 years, 67.5 +/- 7.4 kg, and 170.6 +/- 6.8 cm) participated
in this study and were randomized into either a probiotic (n = 11; DE111) or
placebo (n = 12; PL) group while counterbalancing groups for sport. Athletes
completed a 10-week resistance training program during the offseason, which
consisted of 3-4 workouts per week of upper- and lower-body exercises and sport
specific training. Athletes consumed DE111 (DE111; 5 billion CFU/day) or PL
supplement daily for the entire 10-week program. Before and after training, all
athletes underwent 1 repetition maximum (1RM) strength testing (squat, deadlift,
and bench press), performance testing (vertical jump and pro-agility), and
isometric midthigh pull testing. Body composition (body fat [BF]%) was completed
using BODPOD and bioelectrical impedance analysis, as well as muscle thickness
(MT) measurement of the rectus femoris (RF) and vastus lateralis using
ultrasonography. Separate repeated-measures analyses of variance were used to
analyze all data. Significant (p <= 0.05) main effects for time were observed for
improved squat 1RM, deadlift 1RM, bench press 1RM, vertical jump, RF MT, and BF%.
Of these, a significant group * time interaction was noted for BF% (p = 0.015),
where greater reductions were observed in DE111 (-2.05 +/- 1.38%) compared with
PL (-0.2 +/- 1.6%). No other group differences were observed. These data suggest
that probiotic consumption in conjunction with post-workout nutrition had no
effect on physical performance but may improve body composition in female
Division I soccer and volleyball players after offseason training.
PMID- 29952877
TI - Left Ventricular Mechanics Assessed by 2-dimensional Speckle Tracking
Echocardiography in Children and Adolescents with Idiopathic Scoliosis: Errata.
PMID- 29952876
TI - Preoperative Risk Factors for Recurrent Lumbar Disk Herniation in L5-S1: Errata.
PMID- 29952878
TI - Factors Affecting Patient Decision-making on Surgery for Lumbar Disc Herniation.
AB - STUDY DESIGN: Qualitative research using semi-structured interviews. OBJECTIVE:
To explore, from a patient perspective, factors influencing a patient's decision
making process and the decision to have surgery for lumbar disc herniation.
SUMMARY OF BACKGROUND DATA: Since strong evidence favoring surgical over non
surgical treatment is lacking and firm guidelines regarding the optimal timing of
surgery are not available, it is essential to involve patients in the decision
making process. Thus the elements that might affect the decision-making process
and the decision to have surgery must be identified. METHODS: Using a hermeneutic
phenomenological approach, 14 patients who were referred for primary surgery for
lumbar disc herniation were interviewed. Interviews were transcribed and analyzed
using a meaning-condensation method to identify themes influencing a patient's
decision-making process and the decision to have surgery for lumbar disc
herniation. RESULTS: Four main themes that could directly or indirectly influence
the patients' decision-making process were identified: 1) Patient information:
patients conceptions about treatment were not always based on sufficient
information; 2) Accelerated workflows: some patients needed time to process the
information given, which may be limited due to accelerated workflows; 3) Power
imbalance: patients can be reluctant to challenge the system, as they do not want
to offend, which can be seen as a power imbalance between clinicians and
patients; and 4) Personal past experience: experience, about treatment options
from i.e. close relatives, can impact patients thoughts about possible
treatments. CONCLUSION: Several factors can influence patients' decision-making
process and the decision itself: the amount and quality of information received
as compared to their pre-conceived notions, the amount of time given to consider
their decision, reluctance to challenge the system and offend the healthcare
provider, and past personal experience. Understanding these complex factors will
help clinicians to better support patients choosing between surgical and non
surgical treatment for lumbar herniated disc. LEVEL OF EVIDENCE: 5.
PMID- 29952879
TI - "Bisphosphonate and Teriparatide Use in Thoracolumbar Spinal Fusion: A Systematic
Review and Meta-Analysis of Comparative Studies".
PMID- 29952880
TI - Effectiveness of Kinesio Taping(r) in Patients With Chronic Non-specific Low Back
Pain: A Systematic Review With Meta-analysis.
AB - STUDY DESIGN: Systematic review. OBJECTIVES: To investigate the effects of
Kinesio Taping (KT) in patients with non-specific low back pain. SUMMARY OF
BACKGROUND DATA: KT is widely used in patients with low back pain. METHODS: We
conducted searches on PubMed, EMBASE, PEDro, SciELO and LILACS up to February 26,
2018. We included only randomized controlled trials (RCTs) in adults with chronic
non-specific low back pain that compared KT to no intervention or placebo as well
as RCTs that compared KT combined with exercise against exercise alone. The
methodological quality and statistical reporting of the eligible trials were
measured by the 11-item PEDro scale. The quality of the evidence was assessed
using the GRADE classification. We considered pain intensity and disability as
the primary outcomes. Whenever possible, the data were pooled through meta
analysis. RESULTS: We identified eleven RCTs for this systematic review (pooled n
= 743). Two clinical trials (pooled n = 100) compared KT to no intervention at
the short-term follow-up. Four studies compared KT to placebo (pooled n = 287) at
short-term follow-up and two trials (pooled n = 100) compared KT to placebo at
intermediate-term follow-up. Five trials (pooled n = 296) compared KT combined
with exercises or electrotherapy to exercises or spinal manipulation alone. No
statistically significant difference was found for most comparisons. CONCLUSIONS:
Very low to moderate quality evidence shows that KT was no better than any other
intervention for most the outcomes assessed in patients with chronic non-specific
low back pain. We found no evidence to support the use of KT in clinical practice
for patients with chronic non-specific low back pain. LEVEL OF EVIDENCE: 1.
PMID- 29952881
TI - What Factors Influence Reimbursement for 1-2 Level Anterior Discectomy and Fusion
(ACDF) Procedures?
AB - STUDY DESIGN: Retrospective review OBJECTIVE.: To determine reimbursement
associated with an anterior discectomy and fusion (ACDF) and the demographic
factors influencing reimbursement for an ACDF. SUMMARY OF BACKGROUND DATA: ACDF
has been shown to be a cost-effective procedure. However, there has been minimal
analysis of factors influencing reimbursement for this procedure. METHODS:
Clinical and financial data were retrospectively reviewed for 176 patients
undergoing an ACDF procedure in 2013 and 2014. Patients were included if they had
primary ACDF and excluded if they were treated for a traumatic cervical spine
fracture, infection, failed primary procedure, front/back procedure or total disc
replacement procedure. Clinical factors analyzed included number of levels fused,
surgical time, length of stay in the hospital, estimated blood loss, implant
type, Charleson Comorbidity Index (CCI), and pre-operative diagnosis. Payer type
and reimbursement associated with physician and hospital fees were collected for
each patient. A multiple linear regression model determined the factors
influencing charge and reimbursement data using a backward conditional stepwise
methodology. Variables were only included in multi-variate analysis if there was
a significant (p < 0.05) impact on either reimbursement within univariate
analysis. RESULTS: One hundred and twenty-eight patients met inclusion criteria.
The average reimbursement per patient was $24,622 (+/- standard deviation of
14,616). The only significant factor influencing reimbursement was payer type (p
< 0.001) and length of hospital stay (p < 0.001) and length of hospital stay (p <
0.001) during our UNIVARIATE ANALYSIS.: These two independent multi-variate
determinants of reimbursement only accounted for 18.6% of reimbursement
variability. CONCLUSIONS: There is substantial variability in reimbursement for
ACDF procedures. Multivariate analysis indicates that payer type and length of
hospital stay significantly influence reimbursement. Our model, however, only
explained a small proportion of reimbursement variability indicating that factors
outside our analysis may significantly affect hospital reimbursement. LEVEL OF
EVIDENCE: 3.
PMID- 29952882
TI - Natural History of Cervical Degenerative Spondylolisthesis.
AB - STUDY DESIGN: Retrospective observational and case-control study OBJECTIVE.: To
determine the risk factors for progression of degenerative listhesis by comparing
patients with and without progression at greater than five-year follow-up.
SUMMARY OF BACKGROUND DATA: The previous study with two to seven-year follow-up
showed that degenerative spondylolisthesis of the cervical spine did not
progress. Longer-term follow-up may reveal that these patients actually do
progress over time. METHODS: We identified two hundred eighteen patients with
greater than 5-year follow-up without surgery. They were categorized as either
having or not having cervical spondylolisthesis. We defined spondylolisthesis as
the presence of greater than 2 mm of translation in standing neutral lateral
radiographs of the cervical spine at the initial evaluation. The control group at
baseline was those without spondylolisthesis. Progression of translation was
defined as greater than 2 mm of additional translation on the final standing
neutral radiograph. RESULTS: The mean follow-up duration was 6.4 +/- 1.0 years
(range: 5 to 9.4 years). Progression of translation was found in 20 patients
(9.2%), including 4 patients in the spondylolisthesis group, and 16 patients in
the control group. Progression of translation was not related to the presence of
spondylolisthesis nor the severity of translation at the initial evaluation, but
was more common in the elderly and in the patients with anterior translation than
those with posterior translation at the initial evaluation. In addition,
progression of spondylolisthesis was not correlated with any change of symptoms.
CONCLUSIONS: Progression of cervical spondylolisthesis is not related to the
presence of spondylolisthesis at baseline. LEVEL OF EVIDENCE: 4.
PMID- 29952883
TI - A Technique for Dynamic Cervical Magnetic Resonance Imaging Applied to Cervical
Spondylotic Myelopathy: A Reliability Study.
AB - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate morphometric
variations of the cervical spine in patients with cervical spondylotic myelopathy
(CSM) using a standard technique of dynamic magnetic resonance imaging (MRI), to
assess the inter- and intra-observer reliability of measurements of morphometric
parameters based on this imaging, and to compare the resulting measurements with
those previously published. SUMMARY OF BACKGROUND DATA: Since dynamic factors may
contribute to the etiology and severity of CSM, dynamic (flexion-extension) MRI
may be useful to better evaluate for spinal stenosis and cord compromise.
METHODS: Dynamic cervical MRI was obtained using a standard protocol with the
neck in neutral, flexion, and extension positions. The morphometric parameters
considered were anterior length of the spinal cord (ALSC), posterior length of
the spinal cord (PLSC), spinal canal diameter (SCD) and spinal cord width (SCW).
Two observers analyzed the parameters independently, and the inter- and intra
observer reliabilities were assessed by the intraclass correlation coefficient
(ICC). RESULTS: 18 patients were included in the study and all completed the
dynamic MRI acquisition protocol. The inter- and intra-observer reliabilities
demonstrated "almost perfect agreement" (ICC > 0.9, p < 0.001) for ALSC and PLSC
in all positions. The SCD had inter- and intra-observer reliability classified as
"almost perfect agreement" (ICC: 0.83-0.98, p < 0.001 and ICC: 0.90-0.99, p <
0.001, respectively) in all positions. The SCW had inter- and intra-observer
reliability classified as "substantial agreement" (ICC: 0.73-0.94, p < 0.001 and
ICC: 0.79-0.96, p < 0.001, respectively) in all positions. ALSC and PLSC in
neutral, flexion and extension positions from the present study were
significantly greater compared to the measurements previously published (P <
0.001). CONCLUSION: The dynamic MRI protocol presented was safe and may allow a
more complete evaluation of variations in the cervical spine in patients with CSM
than traditional MRI protocols. The morphometric parameters based on this
protocol demonstrated excellent inter- and intra-observer reliabilities. LEVEL OF
EVIDENCE: 4.
PMID- 29952884
TI - Scoliosis Curvature Follows Thoracic Organ Orientation.
AB - STUDY DESIGN: Retrospective cohort study, Level of Evidence III OBJECTIVE.: To
determine the relationship between internal organ orientation and adolescent
idiopathic scoliosis (AIS) convexity directionality SUMMARY OF BACKGROUND DATA.:
AIS affects 2-3% of the general population and demonstrations 80-99% right
thoracic curve convexity. The mechanism of AIS as well as explanation for right
sided predominance is largely unknown. METHODS: A retrospective chart review of
all patients with dextrocardia from 2008-2018 was performed at a single
institution. Upright chest x-rays and scoliosis x-rays were evaluated for
scoliosis by measurement of Cobb angle. Chart review was performed to extract
age, advanced imaging results, and surgical intervention. RESULTS: Of 110
patients identified with dextrocardia, 19 patients exhibited radiographic
features consistent with AIS (Cobb angle >10 degrees). Fifteen (79%) of these
patients demonstrated left-sided thoracic curvature. Six patients showed isolated
dextrocardia with normal abdominal organ orientation; five patients (83%) showed
left-sided thoracic curvature. There was not a statistical difference with
regards to gender or curve severity. MRI was performed on five patients with left
sided curvature without evidence of intra-spinal pathology. CONCLUSIONS:
Dextrocardia shows increased incidence of AIS in both male and female patients.
Left-sided thoracic curvature in cases with concurrent dextrocardia may not be
associated with intra-spinal pathology as seen in the general population. This
data suggests that thoracic organ orientation affects AIS convexity
directionality. LEVEL OF EVIDENCE: 4.
PMID- 29952885
TI - The Lumbar Artery Perforator Flap in Autologous Breast Reconstruction: Initial
Experience with 100 Cases.
AB - BACKGROUND: The lumbar artery perforator flap is an alternative flap in breast
reconstruction for those patients who are not eligible for a deep inferior
epigastric artery perforator (DIEAP) flap. Shaping of this flap is easier
compared with other flaps because of the quality of the lumbar fat and the
gluteal extension. METHODS: Between October of 2010 and June of 2017, a total of
100 lumbar artery perforator free flap breast reconstructions were performed in
72 patients. Patient demographics, indications, flap specifics, and complications
were reviewed retrospectively. RESULTS: Twenty-eight bilateral and 44 unilateral
breast reconstructions with a lumbar artery perforator flap were performed. Mean
patient age was 48 years, and the average body mass index was 23.11 kg/m. The
authors report 43 preventive mastectomies for elevated cancer risk with
subsequent immediate reconstruction, 34 secondary reconstructions, and 14
tertiary reconstructions. Mean operative time was 7 hours 4 minutes, including
the mastectomy in primary cases. Mean flap weight was 499 g (range, 77 to 1216 g)
and mean follow-up time was 30 months. The revision rate was 22 percent and nine
flaps were lost. CONCLUSIONS: The lumbar artery perforator flap is a valuable
alternative to the DIEAP flap in breast reconstructive surgery. It is an
excellent flap for BRCA-positive patients who are typically young and have
limited excess tissue at the conventional donor sites. Despite higher revision
rates compared with the DIEAP flap, the lumbar flap is superior in mimicking the
shape and feel of native breast tissue. Scarring at the donor site remains a sore
point but can be easily treated and used to an advantage to contour the flanks.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
PMID- 29952886
TI - Comparison between Negative-Pressure Fixation and Film Dressing in Wound
Management after Tissue Expansion: A Randomized Controlled Trial.
AB - Wound compression and fixation are important to reduce scarring. Numerous
postoperative treatments have been developed to reduce scar formation; however, a
simple and effective device that improves the appearance and histochemical
properties of incisional scars is needed. Therefore, the authors have devised a
novel method, negative-pressure fixation, that applies negative pressure inside
polyurethane foam covered with film. In the present study, negative-pressure
fixation was applied to incisional wounds resulting from the insertion of a
tissue expander in patients undergoing two-stage breast reconstruction. The
authors aimed to evaluate the effects of negative-pressure fixation on scar
appearance and histochemical properties in comparison to those for film dressing
without negative pressure. A prospective, open-label, randomized, single-center
study was performed. A half-side test was conducted on the incisional scar
resulting from tissue expander insertion during breast reconstruction after
mastectomy in 13 female patients. The dressings on both sides of the scar were
replaced once per week until the tissue expander was adequately inflated. The
outcomes were assessed 6 months later. Scars were photographed before the second
operation and were evaluated using a visual analogue scale. All scars were
removed and resutured during the final operation, allowing a histochemical
analysis. The mean visual analogue scale score for the negative-pressure fixation
side was significantly lower compared with that for the film dressing side (p =
0.0025). In addition, the scar on the negative-pressure fixation side was
significantly narrower (p = 0.0015). Thus, negative-pressure fixation is a simple
and effective device for improving the appearance and histochemical properties of
incisional scars.
PMID- 29952887
TI - Discussion: Comparison between Negative-Pressure Fixation and Film Dressing in
Wound Management after Tissue Expansion: A Randomized Controlled Trial.
PMID- 29952888
TI - Discussion: Use of Roof-Shaped Costochondral Cartilage for Correction of Saddle
Nose Deformity.
PMID- 29952889
TI - Do Adolescents with Gynecomastia Require Routine Evaluation by Endocrinology?
AB - BACKGROUND: Primary evidence for the role of endocrinologic investigations in
patients with adolescent gynecomastia is lacking in the current literature. The
objective of this study was to assess the yield of endocrinologic investigations
in the evaluation of adolescent gynecomastia to inform current practice for this
common condition. METHODS: A 26-year retrospective review was conducted. Data
collection included patients with gynecomastia presenting to endocrinology at a
quaternary children's hospital with a catchment area of 1 million. Clinical
metrics, endocrinologic results, treatments, and costs were reviewed. RESULTS:
One hundred ninety-seven patients met inclusion criteria. Ninety-eight (50
percent) were overweight or obese and 29 (15 percent) had a positive family
history. The median age at onset was 11.5 years; 25 cases (13 percent) were
prepubertal. A total of 15 patients (7.6 percent) were diagnosed with secondary
gynecomastia (10 related to exogenous substance use). Endocrine investigations
were performed in 173 patients (87 percent), with positive findings in three
cases (1.7 percent). One hundred one patients were observed, with a median age at
resolution of 14.6 years; 86 patients underwent surgery at a median age of 16.5
years. The case-cost of endocrine evaluation was $389. CONCLUSIONS:
Endocrinologic workup identified secondary gynecomastia in 7.6 percent of
patients, of which only 1.7 percent were evident on blood work. This workup is
associated with an avoidable case-cost burden to the health care system and
largely unnecessary testing for the child. Because a majority of secondary
gynecomastia cases (67 percent) were drug-induced, we do not suggest routine
endocrinology workup, as it adds little value. The authors' data suggest that
referral for surgery is warranted if gynecomastia persists beyond 16 years of
age. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.
PMID- 29952890
TI - Discussion: Using the BODY-Q to Understand Impact of Weight Loss, Excess Skin,
and the Need for Body Contouring following Bariatric Surgery.
PMID- 29952891
TI - Treatment of Paradoxical Adipose Hyperplasia following Cryolipolysis: A Single
Center Experience.
AB - : Paradoxical adipose hyperplasia is a rare adverse event associated with
cryolipolysis. No evidence of spontaneous resolution has been described and
little has been written about its treatment. The purpose of this report is to
share the authors' experience treating patients with paradoxical adipose
hyperplasia after cryolipolysis. A retrospective chart review was performed for
all paradoxical adipose hyperplasia patients seen in the authors' practice
between May of 2013 and May of 2016. The treatment parameters, demographics,
onset of findings, and subsequent treatment were chronicled. Eleven cases of
paradoxical adipose hyperplasia were identified (eight men and three women). All
patients were of Hispanic background. Seven patients were treated surgically (six
cases of liposuction alone and one case of liposuction and abdominoplasty).
Average follow-up was 9.6 months (range, 2 to 32 months). Three of the patients
treated with liposuction required a secondary procedure. All surgically treated
patients were very satisfied with their final appearance. Paradoxical adipose
hyperplasia is a rare complication of cryolipolysis that may occur more
frequently than in the manufacturer's reported data. Treatment is best delayed
until the affected area has softened, which normally occurs in 6 to 9 months
after the initial cryolipolysis procedure. Power-assisted liposuction is the
preferred method of treatment, but in some cases, abdominoplasty may be
necessary. Secondary treatments might be needed for recurrence or persistent
bulge. One must be sensitive to heightened patient concerns when offering an
invasive procedure to correct the complications from a noninvasive one. CLINICAL
QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
PMID- 29952892
TI - Discussion: Enhancement of Progenitor Cells by Two-Step Centrifugation of
Emulsified Lipoaspirates.
PMID- 29952893
TI - Evaluation of the In Vivo Kinetics and Biostimulatory Effects of Subcutaneously
Injected Hyaluronic Acid Filler.
AB - BACKGROUND: Because subcutaneously injected hyaluronic acid filler is absorbed
over 6 months to 1 year after the treatment of facial wrinkles, frequent
retreatment may be required. However, persistent long-term effects are often
clinically observed when hyaluronic acid filler is injected as a bolus for facial
augmentation. Therefore, the authors investigated, over time, the changes in
volume and histologic features of subcutaneous bolus injections of hyaluronic
acid. METHODS: Hyaluronic acid filler was subcutaneously injected as a bolus into
the dorsum of 6-week-old rats. At several time points (immediately after
injection and 4, 8, 16, 32, and 64 weeks thereafter), magnetic resonance imaging
was introduced to observe morphologic changes and to measure volume. Histologic
examination of sectioned tissues was also performed. RESULTS: The average volume
increased for up to 4 weeks after injection and then gradually decreased, with
74.8 percent of the injected volume remaining after 64 weeks, with no statistical
difference compared to the initial volume. Histologic analysis revealed that
lattice structures were created by fibroblasts and collagen fibers, and blood
vessels and adipocytes were also generated in the filler. CONCLUSIONS: Although
subcutaneous bolus injections of hyaluronic acid filler exhibited flattening, the
total volume was maintained even after 64 weeks. Histologically, hyaluronic acid
filler acted as a scaffold for autogenous tissue replacement by means of
fibroblast migration and proliferation, collagen induction, and angiogenesis,
followed by proliferation of adipocytes. This study demonstrates that the total
volume is maintained long-term by replacing part of the injected hyaluronic acid
filler with autologous tissues.
PMID- 29952894
TI - Discussion: Evaluation of the In Vivo Kinetics and Biostimulatory Effects of
Subcutaneously Injected Hyaluronic Acid Filler.
PMID- 29952896
TI - Lipomatosis of Nerve: More than a Focal Distal Disease.
AB - Lipomatosis of nerve is a rare, ill-defined, fibrofatty tumor intermingled among
nerve fascicles. The classic presentation of lipomatosis of nerve describes focal
distal involvement of the median nerve at the wrist. The purpose of this study
was to determine the level of proximal lesion extension in cases of upper
extremity lipomatosis of nerve using magnetic resonance imaging. The authors'
study confirms that lipomatosis of nerve is more than a focal distal disease.
Lipomatosis of nerve has the potential for multiple nerve involvement and for
proximal nerve involvement extending to the nerve roots. Magnetic resonance
imaging of the entire upper extremity may be indicated in patients with
lipomatosis of nerve, especially when the ulnar nerve is affected.
PMID- 29952895
TI - Older Patient Preferences for Internal Fixation after a Distal Radius Fracture: A
Qualitative Study from the Wrist and Radius Injury Surgical Trial.
AB - BACKGROUND: Distal radius fracture treatments provide similar functional
outcomes. It has been hypothesized that the use of internal fixation is
increasing because of physician preferences. The multisite randomized Wrist and
Radius Injury Surgical Trial provides a unique opportunity to examine patient
preferences in the absence of surgeon influence. The authors' objective was to
investigate patient preference for internal fixation even after being informed of
the equipoise among treatments. METHODS: The authors performed 30 semistructured
interviews with older individuals, all older than 60 years, approached at their
institution for the Wrist and Radius Injury Surgical Trial. The authors' sample
included three groups: those with a preference for internal fixation (n = 11),
those with preference for nonsurgical treatment (n = 6), and those without a
preference who consented to surgical randomization (n = 13). We used grounded
theory for data collection and analysis. RESULTS: All participants indicated
their chief concern was regaining full function. Patients based their preferences
for internal fixation on multiple values, including obstacles to recovery,
autonomy, aesthetics, and pain relief. Some patients who did not select internal
fixation reflected on their experiences, questioning whether they would have had
a potentially different outcome with internal fixation treatment. CONCLUSIONS:
Without evidence for a superior treatment, patients focus on factors that pertain
to recovery rather than outcomes, with most preferring the volar locking plating
system. To best align with patient values, physicians should focus their
discussion with patients on aspects of the recovery period rather than functional
outcomes. Evidence from the Wrist and Radius Injury Surgical Trial will provide
high-level information about patient-reported, functional, and radiographic
outcomes.
PMID- 29952897
TI - To Admit or Not to Admit: That is the Cleft Lip Question. Confirming the Safety
of Outpatient Cleft Lip Repair.
AB - BACKGROUND: There is no accepted protocol for inpatient versus ambulatory cleft
lip surgery. The aim of this study was to review the safety of outpatient repair
and develop guidelines. METHODS: A retrospective review of patients younger than
2 years undergoing primary cleft lip repair from 2008 to 2015 at six centers was
performed. Patients were divided into two groups: predominantly ambulatory
(discharged or admitted for specific concerns) and inpatient (admitted due to
surgeon's preference). The impact of independent variables on admission,
emergency department visits, and readmission within 1 month of discharge was
analyzed. RESULTS: Of 546 patients, 68.1 percent were boys, 4.4 percent had
syndromes, and 23.6 percent had comorbidities. One hundred forty-two patients
were admitted postoperatively. Forty-nine admissions were attributable to the
surgeon's preference. After excluding this subset, our ambulatory surgery rate
was 81 percent. There was no difference in emergency department visits (3 percent
versus 2.2 percent; p = 0.6) or readmissions (0 percent versus 1.45 percent; p =
0.5) between groups. None of the ambulatory surgery patients were readmitted
within 36 hours, for a successful ambulatory surgery rate of 100 percent. Female
sex; surgical time; prematurity and/or postconceptional age younger than 52
weeks; and cardiac, respiratory, central nervous system, gastrointestinal,
genitourinary, and other congenital comorbidities had significant impact on
admission rates in the predominantly ambulatory group (p < 0.05). Respiratory
comorbidities and syndromes were risk factors for readmission if patients
presented to the emergency department (p < 0.05). CONCLUSIONS: Ambulatory cleft
lip repair can be performed safely in most patients with no difference in
emergency department visits or readmission. Patients with comorbidities should be
admitted for observation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
PMID- 29952898
TI - Reconstruction of Microtia Using a Single Expanded Postauricular Flap without
Skin Grafting: Experience of 683 Cases.
AB - BACKGROUND: Auricular reconstruction of congenital microtia patients is a huge
challenge for plastic surgeons worldwide. Current techniques usually use a
retroauricular fascial flap with skin grafting, often proving to be color
mismatched, complex, and with visible scarring. An uncomplicated strategy that
results in minimal scarring and a good color match is still required, especially
for Asian patients. In the present work, the authors developed a modified
technique for auricular reconstruction using a single expanded flap combined with
a cartilage framework. METHODS: Auricular reconstruction was performed in three
stages. In the first stage, an 80-ml kidney-shaped expander was inserted in the
mastoid region. A gradual expansion period of approximately 2 to 3 months was
implemented until the flap achieved an appropriate area, thickness, and softness.
In the second stage, the expander was removed and a modified three-layer
cartilage framework was inserted into the pocket through the same incision. In
the third stage, the reconstructed ear underwent further refinements, including
reconstruction of the earlobe and tragus. RESULTS: From January of 2012 to
January of 2017, 683 microtia patients (a total of 738 ears) were selected for
auricular reconstruction using this technique. The patients were followed up for
between 3 months and 2 years. Six hundred forty-two patients were satisfied with
the final results regarding the size, shape, projection, symmetry, and clarity of
outline. Surgery-related complications occurred in 20 patients. CONCLUSION:
Auricular reconstruction using a single expanded flap combined with a modified
three-layer cartilage framework is an effective and efficient technique for
microtia reconstruction with satisfying medium-term results. CLINICAL
QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
PMID- 29952899
TI - Discussion: Pediatric Zygomaticomaxillary Complex Fracture Repair: Location and
Number of Fixation Sites in Growing Children.
PMID- 29952900
TI - Segmental Multiple-Jaw Surgery without Orthodontia: Clear Aligners Alone.
AB - Segmental Le Fort I osteotomy, a complex procedure with many mobile parts, has
traditionally required presurgical orthodontics with conventional braces,
composed of metal brackets, bands, and archwires. These appliances are not always
accepted by patients, particularly older teenagers and professional adults who
previously endured traditional orthodontia during adolescence, and now require
retreatment because of jaw growth differences necessitating orthognathic surgery.
Less obtrusive orthodontic therapies, involving clear aligners (e.g.,
Invisalign), are becoming increasingly popular, as they are less noticeable and
less aesthetically objectionable. They are typically indicated for milder
occlusal discrepancies, such as crowding and minor rotations, without significant
vertical or transverse problems. Clear aligners in conjunction with orthognathic
surgery for severe dentofacial problems are progressive and not widely used.
Moreover, the most complicated of orthognathic sequences, segmental double-jaw
surgery, has never before been described to be performed using Invisalign.
Several potential challenges exist when performing segmental double-jaw surgery
with Invisalign (i.e., no bonded or banded appliances, and no archwire). The
purpose of this article is to review the feasibility of segmental double-jaw
surgery without orthodontia (Invisalign only), report a series of cases, and
review the technical steps involved.
PMID- 29952901
TI - Discussion: Incomplete Facial Paralysis: The Use of the Ipsilateral Residual
Facial Nerve as a Donor Nerve for Facial Reanimation.
PMID- 29952902
TI - Fournier Gangrene: Association of Mortality with the Complete Blood Count
Parameters.
AB - BACKGROUND: The authors studied the alterations in mean platelet volume,
neutrophil-to-lymphocyte ratio, and red blood cell distribution width values
together with the platelet count in hospitalized patients diagnosed with Fournier
gangrene to determine their association with disease prognosis. METHODS: Records
of patients diagnosed with Fournier gangrene were analyzed retrospectively.
RESULTS: Seventy-four patients (49 men and 25 women) with a mean age of 57.60 +/-
15.34 years (range, 20 to 95 years) were included. Sixty-eight participants were
discharged and six died during follow-up. In the discharged group, during
hospitalization, there was a trend downward in neutrophil-to-lymphocyte ratio and
mean platelet volume values, whereas platelet count increased significantly. In
the nonsurvivor group, the neutrophil-to-lymphocyte ratio and mean platelet
volume after first debridement and at the end of hospitalization were
significantly higher; platelet counts at admission, after the first debridement,
and at the end of hospitalization were significantly lower compared with the
survivor group (p < 0.05). In correlation analysis, mortality rate was negatively
correlated with platelet count at admission and after first debridement and
positively correlated with the neutrophil-to-lymphocyte ratio and mean platelet
volume after first debridement. Regarding the receiver operating characteristic
curve analyses, a platelet count of 188,500/ul at admission and 196,000/ul after
the first debridement, a neutrophil-to-lymphocyte ratio of 13.71, and a mean
platelet volume of 9.25 fl after the first debridement were defined as the cutoff
levels having the best sensitivities and specificities. CONCLUSIONS: This study
suggests that platelet count at admission and platelet count, mean platelet
volume, and neutrophil-to-lymphocyte ratio after first debridement and during
discharge may be included among the prognostic scores of Fournier gangrene. The
authors defined some threshold values that can be used during patient follow-up.
Larger prospective studies are warranted to determine the exact role of those
parameters in the prognosis of Fournier gangrene. CLINICAL QUESTION/LEVEL OF
EVIDENCE: Risk, III.
PMID- 29952903
TI - Personal Safety of the Plastic Surgeon: Keeping Yourself Healthy While You Work.
AB - LEARNING OBJECTIVES: After reading this study, the participant should be able to:
1. Recognize the primary physical and mental risks faced by the practicing
plastic surgeon. 2. State the primary risk factors for cervical spine disease and
back pain. 3. State the critical steps for protection from ionizing and
nonionizing radiation. 4. List the characteristics of a surgeon exhibiting signs
of burnout. 5. Develop a plan for mitigating personal risk of musculoskeletal,
exposure, and other injuries. SUMMARY: Health care workers are exposed to
significant occupational hazards, and have a risk of injury similar to that of
construction, mining, and manufacturing employees. Plastic surgeons must have a
clear understanding of the types of risks they face and the techniques for
mitigating them. Exposure to some risks is attributable to unavoidable
occupational conditions, but others can be avoided completely. The sources of
injury risk from musculoskeletal, exposure, and other causes are discussed in
this article, and evidence-based recommendations to ameliorate these risks are
presented.
PMID- 29952904
TI - Discussion: The Impact of Once- versus Twice-Daily Enoxaparin Prophylaxis on Risk
for Venous Thromboembolism and Clinically Relevant Bleeding.
PMID- 29952905
TI - Gender Differences in the Professional and Personal Lives of Plastic Surgeons.
AB - BACKGROUND: Although the number of women becoming plastic surgeons has increased
during the past six decades, in comparison with the current gender parity in
medical schools, plastic surgery still attracts disproportionately more men.
Previous studies have shown disparities in the professional and personal lives of
female and male plastic surgeons. A survey study was conducted to identify
current challenges women and men encounter in the pursuit of a plastic surgical
career to guide remedial strategies. METHODS: An anonymous electronic survey was
distributed to American Society of Plastic Surgeons members and candidates for
comparison between sexes. Differences were tested by the Fisher's exact and chi
square tests. RESULTS: Women were more likely than men to have experienced sexism
or bias. Women were less likely to be married; be satisfied with work-life
balance; or feel recognized for ideas, authorship, promotions, or raises. Women
felt that their sex was a disadvantage in career advancement, with one exception:
unlike men, women felt many patients chose them because of their sex. Despite
these challenges, over 80 percent of all plastic surgeons were satisfied with
their choice of career. CONCLUSIONS: Traditions and gender bias create
disparities in the personal and professional lives of female and male plastic
surgeons. Our specialty must make concrete changes to promote all plastic
surgeons, both women and men, to thrive personally and professionally.
PMID- 29952906
TI - What Does the Public Think? Examining Plastic Surgery Perceptions through the
Twitterverse.
AB - BACKGROUND: Twitter is a recognized social media platform for communication of
health information. Rime reported that emotion is the main motive for social
sharing. This study is a content analysis of Twitter that was performed to
identify the public's perceptions and attitudes toward plastic surgery and the
emotional triggers that drive social sharing of plastic surgery information.
METHODS: Tweets containing "#PlasticSurgery" or "Plastic Surgery" were archived
randomly from August 1, 2014, to December 30, 2016 (n = 4548). Tweets were
categorized according to tweet author, specialty, topic, content, multimedia
included, emotion, tone, accuracy of information, source, and retweet rate.
Statistical analysis was performed to detect significant patterns. RESULTS:
Tweets on cosmetic surgery (74 percent) were shared mostly on Twitter,
predominantly posted by the public [n = 1611 (48 percent)]. More than 13 percent
of posts contained "celebrity news" and 42.8 percent contained professional
information and resources. The most frequent emotions shared and retweeted were
"relaxed/content" (51.5 percent) and "excited/interested" (18.4 percent). Most
tweets posted by the public contained inaccurate information [n = 1486 (80
percent)]. Only 154 (11.2 percent) of board-certified plastic surgeons' tweets
were rated as "most accurate." CONCLUSIONS: The majority of tweets posted on
Twitter contained inaccurate information that can lead to misperception among the
public. Understanding emotional triggers for social sharing provides insight into
what is most appealing. To enhance public uptake and sharing of tweets, plastic
surgeons can use these findings to promote the specialty using relaxed/content
emotions or excitement in their social media posts.
PMID- 29952907
TI - Discussion: What Does the Public Think? Examining Plastic Surgery Perceptions
through the Twitterverse.
PMID- 29952908
TI - Discussion: What Does the Public Think? Examining Plastic Surgery Perceptions
through the Twitterverse.
PMID- 29952909
TI - Outcomes for the Journal: Introduction of Four Subdomains.
PMID- 29952910
TI - Common Sense for the Common Good: Staying Subcutaneous during Fat Transplantation
to the Gluteal Region.
PMID- 29952911
TI - Helpful Hints for the Superficial Temporal Artery and Vein as Recipient Vessels:
Correction.
PMID- 29952912
TI - Comparison of Patient-Reported Outcome Measurements and Objective Measurements
after Cubital Tunnel Decompression: Correction.
PMID- 29952913
TI - Expansion Vibration Lipofilling: A New Technique in Large-Volume Fat
Transplantation: Correction.
PMID- 29952914
TI - Validated Outcomes in the Grafting of Autologous Fat to the Breast: The VOGUE
Study. Development of a Core Outcome Set for Research and Audit: Correction.
PMID- 29952915
TI - Direct-to-Implant versus Two-Stage Tissue Expander/Implant Reconstruction: 2-Year
Risks and Patient-Reported Outcomes from a Prospective, Multicenter Study.
PMID- 29952916
TI - The Inside-Out Septal Mucoperichondrial Flap: Reconstruction of Nasal Lining
Simplified.
PMID- 29952917
TI - Reply: The Inside-Out Septal Mucoperichondrial Flap: Reconstruction of Nasal
Lining Simplified.
PMID- 29952919
TI - CHARACTERIZATION OF THE CHOROIDAL VASCULATURE IN MYOPIC MACULOPATHY WITH OPTICAL
COHERENCE TOMOGRAPHIC ANGIOGRAPHY.
AB - PURPOSE: To characterize the choriocapillaris (CC) in highly myopic eyes with
myopic maculopathy, using optical coherence tomographic angiography. METHODS:
Prospective, clinic-based study of 42 eyes of 38 patients with high myopia (<=-6
diopters and axial length >=26.5 mm). Myopic maculopathy was graded from fundus
photographs according to the Meta-Analysis for Pathologic Myopia classification.
Macular 3 * 3 mm en face optical coherence tomographic angiographic images were
obtained with swept-source optical coherence tomographic angiography and graded
for CC flow impairment as follows: 1) intact CC, 2) focal (<1 mm), and 3)
extensive (>1 mm). RESULTS: Of the 42 eyes, 17 (39.5%) had tessellated fundus, 20
(46.5%) had diffuse, and 6 (14.0%) had patchy atrophy. Choriocapillaris flow
impairment was observed in all eyes with diffuse and patchy atrophy. Even in eyes
with tessellated fundus only, CC signal voids were seen in 3 eyes (17.6%). With
increasingly severe myopic maculopathy, the pattern of CC flow impairment changed
from predominantly focal to predominantly extensive. CONCLUSION: Choriocapillaris
flow impairment was observed in many highly myopic eyes, even in those with mild
fundus changes, and worsened with increasing severity of myopic maculopathy.
Longitudinal studies are needed to assess whether CC flow impairment predicts the
risk of myopic maculopathy progression.
PMID- 29952918
TI - Upper Lip Reconstruction.
PMID- 29952922
TI - Stop TRPC5 in Kidney Disease: A Game Changer for Renal Allograft Protection?
PMID- 29952920
TI - Heart Transplantation in the Middle East Gulf Region.
PMID- 29952923
TI - Yolanda Becker, MD: President of UNOS, Professor of Surgery, University of
Chicago.
PMID- 29952924
TI - Outcomes of Donation After Circulatory Death Liver Grafts From Donors 50 Years or
Older: A Multicenter Analysis.
AB - BACKGROUND: As the population in the United States continues to age, an increase
in the number of potential donation after circulatory death (DCD) donors with
advanced chronological age can be expected. The aim of this study was to analyze
a multi-institutional experience in liver transplantation using DCD donors 50
years or older. METHODS: All DCD liver transplant (LT) performed at Mayo Clinic
Florida, Mayo Clinic Rochester, and Mayo Clinic Arizona from 2002 to 2016 were
included. Recipients of DCD LT were divided into 2 groups: those with donors 50
years or older (N = 155) and those with donors younger than 50 years(N = 316).
RESULTS: Graft survival was similar between the DCD donors 50 years or older
group and DCD donors younger than 50 group(P = 0.99). Graft survival at 1, 3, and
5 years was 87.0%, 75.6%, and 71.8% in the DCD donors 50 years or older group and
85.8%, 76.0%, and 70.4% in the DCD donors younger than 50 group.The rate of total
biliary complications (32.3% vs 23.7%; P = 0.049) and of anastomotic strictures
(16.1% vs 8.2%; P = 0.01) were higher in the DCD donors 50 years or older
compared with the DCD donors younger than 50 group. No statistical significant
difference in the rate of ischemic cholangiopathy (11.6% vs 7.6%; P = 0.15) was
seen between the 2 groups. Due to homogeneous practice patterns at the involved
institutions, additional Cox regression analysis using national data obtained
from Scientific Registry of Transplant Recipients was used to evaluate predictors
of graft failure in DCD donors 50 years or older. Significant predictors of graft
failure included: a calculated Model for End-Stage Liver Disease score of 30 or
higher (P < 0.001), mechanical ventilation at the time of transplant (P < 0.001),
medical condition (in intensive care unit) (P = 0.002), and cold ischemia time (P
< 0.001). CONCLUSIONS: The present study demonstrates that acceptable graft and
patient survival can be achieved with the usage of DCD LT with donors 50 years or
older. Optimizing recipient selection criteria and minimizing cold ischemia time
may further improve outcomes.
PMID- 29952925
TI - Landscape of Living Multiorgan Donation in the United States: A Registry-Based
Cohort Study.
AB - BACKGROUND: The donation of multiple allografts from a single living donor is a
rare practice, and the patient characteristics and outcomes associated with these
procedures are not well described. METHODS: Using the Scientific Registry of
Transplant Recipients, we identified 101 living multiorgan donors and their 133
recipients. RESULTS: The 49 sequential (donations during separate procedures)
multiorgan donors provided grafts to 81 recipients: 21 kidney-then-liver, 15
liver-then-kidney, 5 lung-then-kidney, 3 liver-then-intestine, 3 kidney-then
pancreas, 1 lung-then-liver, and 1 pancreas-then-kidney. Of these donors, 38%
donated 2 grafts to the same recipient and 15% donated 2 grafts as non-directed
donors. Compared to recipients from first-time, single organ living donors,
recipients from second-time living donors had similar graft and patient survival.
The 52 simultaneous (multiple donations during one procedure) multiorgan donors
provided 2 grafts to 1 recipient each: 48 kidney-pancreas and 4 liver-intestine.
Donors had median of 13.4 years (interquartile range, 8.3-18.5 years) of follow
up. There was one reported death of a sequential donor (2.5 years after second
donation). Few postdonation complications were reported over a median of 116 days
(interquartile range, 0-295 days) of follow-up; however, routine living donor
follow-up data were sparse. Recipients of kidneys from second-time living donors
had similar graft (P = 0.2) and patient survival (P = 0.4) when compared with
recipients from first-time living donors. Similarly, recipients of livers from
second-time living donors had similar graft survival (P = 0.9) and patient
survival (P = 0.7) when compared with recipients from first-time living donors.
CONCLUSIONS: Careful documentation of outcomes is needed to ensure ethical
practices in selection, informed consent, and postdonation care of this unique
donor community.
PMID- 29952926
TI - Biomarkers and Kidney Transplant: Time for a New Paradigm?: Erratum.
PMID- 29952927
TI - mTOR Inhibition and Clinical Transplantation: Heart: Erratum.
PMID- 29952928
TI - Validation of the Prognostic Kidney Donor Risk Index (KDRI) Scoring System of
Deceased Donors for Renal Transplantation in the Netherlands: Erratum.
PMID- 29952929
TI - New Answers to Old Conundrums: What Antibodies, Exosomes and Inflammasomes Bring
to the Conversation. Canadian National Transplant Research Program International
Summit Report: Erratum.
PMID- 29952930
TI - Phi, Fat, and the Mathematics of a Beautiful Midface.
AB - PURPOSE: The Golden ratio, or Phi, has been used to explain the substrates of two
dimensional beauty utilizing the faces of models. A "Phi point" has been
identified at the apex of the cheek mound that can be targeted in filler
injections. The authors report herein how they have applied this algorithm for
surgical shaping of the "beautiful" cheek as a routine part of their lower
blepharoplasty procedure. The authors present their technique and results with
patients undergoing lower blepharoplasty along with the adjunct of liposculpture
to areas of volume deficiency in the midface with a particular goal of enhancing
the Phi point. METHODS: This study was retrospective, consecutive, nonrandomized,
interventional case series. The authors reviewed the medical records of 113
consecutive patients who underwent lower blepharoplasty with autologous fat
transfer to the Phi point. The aesthetic outcome, patient satisfaction, and
complication/revisions were evaluated. RESULTS: One hundred two out of 113
patients achieved excellent lower lid position and cheek enhancement as assessed
by both patient and surgeon. In these 102 patients, there was significant
improvement in lower lid appearance, contour, transition to the cheek, and cheek
projection as observed by the surgeon. Three patients required revision to
achieve sufficient volume. Eight patients were satisfied with the outcome,
nevertheless, requested additional filler injection to optimize. CONCLUSIONS:
Lower blepharoplasty combined with autologous fat transfer to reshape the Phi
point is a safe and reliable technique and another step further in our quest for
recreating the beautiful face.
PMID- 29952931
TI - Grading Severity and Activity in Thyroid Eye Disease.
AB - PURPOSE: Thyroid eye disease (TED) is an autoimmune disorder causing
inflammation, expansion, and fibrosis of orbital fat, muscle, and lacrimal gland.
This article reviews the different methods of grading severity and activity of
TED and focuses on the VISA Classification for disease evaluation and planning
management. METHODS: Accurate evaluation of the clinical features of TED is
essential for early diagnosis, identification of high-risk disease, planning
medical and surgical intervention, and assessing response to therapy. Evaluation
of the activity and severity of TED is based on a number of clinical features:
appearance and exposure, periorbital tissue inflammation and congestion,
restricted ocular motility and strabismus, and dysthyroid optic neuropathy. The
authors review these clinical features in relation to disease activity and
severity. RESULTS: Several classification systems have been devised to grade
severity of these clinical manifestations. These include the NO SPECS
Classification, the European Group on Graves Orbitopathy severity scale, the
Clinical Activity Score of Mourits, and the VISA Classification as outlined here.
The authors compare and contrast these evaluation schemes. CONCLUSIONS: An
accurate clinical assessment of TED, including grading of disease severity and
activity, is necessary for early diagnosis, recognition of those cases likely to
develop more serious complications, and appropriate management planning. The VISA
Classification grades both disease severity and activity using subjective and
objective inputs. It organizes the clinical features of TED into 4 discrete
groupings: V (vision, dysthyroid optic neuropathy); I (inflammation, congestion);
S (strabismus, motility restriction); A (appearance, exposure). The layout
follows the usual sequence of the eye examination and facilitates comparison of
measurements between visits and data collation for research.
PMID- 29952932
TI - Nasolacrimal Sac Diverticulum: A Case Series and Literature Review.
AB - PURPOSE: To describe the demographics, presentation, treatment, and outcome in 10
cases of lacrimal sac diverticulum and to review the literature on this topic,
and to determine the incidence of diverticula from a series of dacryocystograms.
METHODS: Data were collected for all consecutive patients with lacrimal sac
diverticulum seen between 2003 and 2015, including patient demographics, clinical
presentation, imaging findings, treatment, and follow-up. A systematic literature
review was performed for cases of lacrimal sac diverticulum. A retrospective
review of 400 consecutive dacryocystograms was performed to determine the
incidence of lacrimal sac diverticulum. RESULTS: Ten cases (9 patients) of
lacrimal sac diverticulum are described, and a further 36 cases were discovered
through a literature review. Epiphora, swelling, and dacryocystitis and/or
diverticulitis were the most common presenting complaints. When all 46 cases are
combined, lacrimal patency was demonstrated in 50% of cases. Dacryocystography
diagnosed only 57% of patients with diverticulum, not helped by the addition of
ultrasound or CT. The incidence of diverticulum was 3.2% on review of 400
consecutive dacryocystograms (1.6% per lacrimal system). Surgical management with
dacryocystorhinostomy and/or diverticulum excision was effective in all 34
operated cases at resolving symptoms in the case series and literature review.
CONCLUSIONS: Lacrimal sac diverticula present with epiphora, medial canthal
swelling, dacryocystitis, and/or diverticulitis. Dacryocystography, despite being
the most sensitive radiologic test, is only 59% sensitive, and adjunctive CT and
ultrasound have limited use. Surgical management is recommended because
conservative management often fails. Dacryocystorhinostomy, diverticulum
excision, or a combination thereof appears to be equivalent in achieving
resolution of symptoms.
PMID- 29952933
TI - Orbital, Periorbital, and Intracranial Emphysema Caused by Compressed Air Injury
in a 5-Year-Old Child.
AB - A 5-year-old boy was accidentally injured by a compressed air blast to his right
eye and developed periorbital and subconjunctival emphysema and proptosis
subsequently. CT scan showed periorbital subcutaneous and intraorbital emphysema
around the right eye, as well as intracranial and cervical emphysema without
frank fractures in orbital bones. He was examined under sedation, and the
subconjunctival air was aspirated. He was also prophylactically treated with
topical and systemic antibiotics to prevent infection. Emphysema was resorbed
entirely within 3 weeks. In conclusion, compressed air injury can occur in a
child and manifest with orbital and periorbital emphysema without any detectable
fracture and any clear entrance site and may need emergent management to save the
vision or upper respiratory airways.
PMID- 29952934
TI - Article Summaries for July-August 2018 Psychosomatic Medicine, Volume 80, Issue
6.
PMID- 29952936
TI - Angiotensin II-Mediated Increases in Damage-Associated Molecular Patterns During
Acute Mental Stress: Erratum.
PMID- 29952937
TI - Validation of the Fusion Risk Score for Thoracic and Lumbar Spine Fusion
Procedures.
AB - STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: This study aimed
to determine whether the Fusion Risk Score (FRS) is valid for perioperative
complications. SUMMARY OF BACKGROUND DATA: The FRS was previously formulated from
a retrospective review of 364 fusion surgeries in patients over age 65. Patient
demographics, comorbidities, surgical approach, levels, and osteotomies are
incorporated in a weighted manner. This score correlated well with the risk of
perioperative complications, operative time, estimated blood loss during surgery,
and length of hospital stay. MATERIALS AND METHODS: A new cohort of patients was
studied. Subjects were 65 years old or older and had undergone routine elective
thoracic or lumbar fusion surgery. The FRS was calculated for each subject to
estimate risk (low, medium, or high) for perioperative complications. Actual
incidences of major complications in the first 90 days after the surgery were
noted and statistically compared with the predicted risk. The FRS was compared
with intensive care unit admittance, estimated blood loss, operative time, and
hospital length of stay to determine whether the score was predictive. RESULTS:
In total, 51% of our patients were at low risk (FRS, 1-3) for perioperative
complications; 43% were at medium risk (FRS, 4-9); and 7% were at high risk (FRS,
over 9). A total of 8% in the low-risk group, 23% in the medium-risk group, and
67% in the high-risk group actually developed significant perioperative
complications. Medium-risk and high-risk patients experienced proportionally more
perioperative complications than did low-risk patients; the difference was highly
statistically significant. CONCLUSIONS: This study validated the association
between the FRS and complications in the first 90 days after thoracolumbar spinal
fusion surgery on the basis of patient and surgery characteristics. It also
predicts the risk of intensive care unit admission, operative time, blood loss,
and hospital length of stay.
PMID- 29952935
TI - Chronic Physiologic Effects of Stress Among Lesbian, Gay, and Bisexual Adults:
Results From the National Health and Nutrition Examination Survey.
AB - OBJECTIVE: Social disadvantage is associated with markers of physiological
dysregulation, which is linked to disease trajectories. Chronic experiences with
discrimination are thought to result in the accumulation of physiological "wear
and tear" known as allostatic load (AL) among socially marginalized populations
such as sexual minorities. Using a nationally representative US sample, we
examined whether (1) people who self-identified as homosexual or bisexual display
higher levels of AL than heterosexual individuals and (2) subgroups of sexual
identity would further differ from each other as a consequence of distinct
experiences of marginalization. METHODS: We use data from the 2001-2010 National
Health and Nutrition Examination Survey. Employing multivariate regression
methods with sex-specific analyses, we examined AL score differences among
lesbian/gay (n = 211), bisexual (n = 307), homosexually experienced (n = 424),
and exclusively heterosexual (n = 12,969) individuals, adjusting for possible
confounding due to demographics, health indicators, and, among men, HIV infection
status. RESULTS: Results indicate that elevated AL was more common in bisexual
men compared with exclusively heterosexual men (adjusted beta = 0.25, 95%
confidence interval [CI] = 0.05 to 0.44), with significantly higher levels of
glycosylated hemoglobin A1c (adjusted odd ratio = 3.51, 95% CI = 1.46-7.92) and
systolic blood pressure (adjusted odd ratio = 2.07, 95% CI = 1.02 to 4.18). Gay
identified men evidenced significantly lower AL (adjusted beta = -0.22, 95% CI =
0.41 to -0.04). No significant differences in AL were observed among women.
CONCLUSIONS: These findings indicate that physiological dysregulation is more
common in bisexual males compared with all other men. The results are discussed
with regard to differences in health outcomes between individuals with different
sexual orientations.
PMID- 29952938
TI - A retrospective study of supplemental iron intake in singleton pregnancy women
with risk of developing gestational diabetes mellitus.
AB - This study investigated the effect of supplemental iron intake (SII) in early
singleton pregnancy women with the risk of developing gestational diabetes
mellitus (GDM) among Chinese population.This study included 259 singleton
pregnancy participants. Of those, 135 women underwent SII and were assigned to an
intervention group, while 124 participants received no SII and were assigned to a
control group. The outcome measurements consisted of the number of patients with
GDM development, the levels of hemoglobin (Hb) and ferritin, and the outcomes of
infant at delivery.No significant difference in the number of patients with GDM
development was found between 2 groups at delivery. However, when compared with
control group, subjects in the intervention group showed greater efficacy in
delivery mode choice of vaginal delivery (P = .04), and cesarean section (P =
.01), as well as the birthweight of infants (P < .01). Moreover, Hb and ferritin
levels were also significantly higher in the intervention group than those in the
control group (P < .01).The results of this retrospective study showed that SII
may not increase risk of developing GDM in singleton pregnancy women; and also
may benefit both pregnancy women and infants among Chinese population.
PMID- 29952939
TI - Level of uric acid and uric acid/creatinine ratios in correlation with stage of
Parkinson disease.
AB - This study aims to investigate relationship between the level of uric acid (UA)
and UA/creatinine ratios (UA/Cr) to the stage of Parkinson disease (PD).A total
of 120 cases of PD patients who were admitted in our hospital between 2013 and
2015 were enrolled into this study; these 120 cases of PD patients were divided
into 3 groups, according to Hoehn-Yahr (H-Y) classification: early stage (1-2
classification), medium stage (2.5-3 classification), and advanced stage (4-5
classification); UA and UA/Cr level in each group was compared. Then, factors
including age, gender, dopamine dosage, UA, and UA/Cr levels were analyzed to
find the independent predictive factors of PD by logistic regression.UA and UA/Cr
levels in the early and medium stage PD patients were significantly higher than
in the advanced stage ones. UA and UA/Cr levels in patients with good prognosis
were significantly higher than in the poor ones.UA and UA/Cr levels are
negatively correlated with the stages of PD and are independent negatively
predicting biological indexes of PD incidence and progression.
PMID- 29952940
TI - Recurrence of anti-MDA5 antibody-positive clinically amyopathic dermatomyositis
after long-term remission: A case report.
AB - RATIONALE: Among all dermatomyositis (DM) patients, antimelanoma differentiation
associated gene 5 antibody (anti-MDA5 Ab) positive patients have significantly
poor short-term mortality, whereas they experience less relapses over the long
term after the remission. We report the case of a patient with anti-MDA5 Ab
positive clinically amyopathic dermatomyositis (CADM) with the recurrence of
interstitial lung disease (ILD) after 7 years of remission. There has been no
case report of an anti-MDA5 Ab-positive DM patient with the recurrence of ILD
after 7 years of long-term remission. PATIENT CONCERNS: A 70-year-old Japanese
woman was diagnosed with anti-MDA5 Ab-positive CADM and ILD. After achieving 7
years long-term remission, she was admitted to our department with erythema on
the fingers and interstitial pneumonia. Her anti-MDA5 Ab titer was elevated.
DIAGNOSES: We diagnosed recurrent CADM complicated with ILD. INTERVENTIONS: We
successfully treated her with 1,000 mg of methyl-prednisolone pulse and
intravenous cyclophosphamide therapy followed by prednisolone 50 mg/day and an
increase of cyclosporine. OUTCOMES: After that treatment, the patient's skin
symptoms and interstitial pneumonia were relieved. All laboratory investigations
such as ferritin, the serum markers of interstitial pneumonia (i.e., SP-A, SP-D),
and the titer of anti-MDA5 Ab showed signs of improvement. LESSONS: Her case
suggests that careful physical examinations and monitoring the serum markers are
important even after long-term remission is achieved.
PMID- 29952941
TI - Pseudoaneurysm rupture with hemorrhagic shock in a patient with periprosthetic
hip joint infection: A case report.
AB - RATIONALE: Although pseudoaneurysm (PA) formation following primary and revision
total hip arthroplasty (THA) is rare, PA rupture may lead to severe complications
that can result in a threat to life and limb. PATIENT CONCERNS: A 65-year-old man
presented with acute hemorrhagic discharge for one day from the chronic hip sinus
secondary to revision THA that had been performed 6 years ago, for which he had
received multiple courses of debridement, antibiotics, and implant retention
procedures owing to periprosthetic joint infection (PJI). DIAGNOSES: Radiographs
showed septic loosening of both the femoral and acetabular components, with
medial migration of the component beyond Kohler's line. Contrast-enhanced
computed tomography angiogram of the abdomen and pelvis of the patient
demonstrated a large PA of the right external iliac artery (EIA), measuring 6.1
cm * 7.7 cm in diameter and 9.1 cm in length. INTERVENTIONS: A ball-shaped
antibiotic-loaded cement spacer (ALCS) was used to tamponade a bleeding PA, treat
the coexisting PJI, and thus facilitate endovascular stent-graft repair (ESGR)
later on. OUTCOMES: The ESGR resulted in complete exclusion of the PA and
successfully controlled the bleeding. The patient underwent a successful revision
THA 6 months after stent insertion. Neither stent-graft infection nor recurrent
PJI were detected at 18 months. LESSONS: Given the potential of a PA for causing
significant morbidity and mortality, the surgeon should have an elevated index of
suspicion in the presence of intrapelvic migration of the acetabular component.
While facing a PA rupture with/without hemorrhagic shock in patients with
coexisting hip PJI, ALCS ball implantation and subsequent ESGR might be an
effective method to save the patient's life and limb.
PMID- 29952942
TI - Vitamin D status in South Korean population: Seven-year trend from the KNHANES.
AB - Vitamin D deficiency has become one of the most prevalent health problems in
modern society. However, there has been no study that has reported the trend of
vitamin D status in Asia. We performed an observational study to investigate the
trend of vitamin D status in South Korea based on a representative national
database acquired from the Korea National Health and Nutrition Examination
Surveys (KNHANES) conducted from 2008 to 2014. A total of 39,759 patients were
included in the final analyses. Serum 25-hydroxyvitamin D (25 (OH)D) levels were
measured by radioimmunoassay. The overall mean serum level of 25 (OH)D was 45.7
nmol/L in males and 40.9 nmol/L in females in KNHANES 2008 to 2014. There was a
significant trend toward lower serum 25 (OH)D levels from 2008 to 2014 in males
by -1.2 (95% confidence interval [CI] -1.5 to -0.9) nmol/L per year and in female
by -0.7 (95% CI -0.9 to -0.4) nmol/L per year. The overall mean serum level of 25
(OH)D in 2008 was 53.0 nmol/L in males and 45.7 nmol/L in females. It decreased
to 43.2 nmol/L in males and 39.2 nmol/L in females in 2014. Vitamin D deficiency,
defined as the serum 25 (OH)D level of <50 nmol/L, was found in 65.7% of males
and 76.7% of females in overall population. A significant increasing trend of
vitamin D deficiency was also observed. The prevalence of vitamin D deficiency in
2008 was 51.8% in males and 68.2% in females, but rose to 75.2% and 82.5%,
respectively, in 2014. The present study demonstrated that vitamin D status in
South Koreans is still deteriorating. More extensive and proactive measures are
needed to improve vitamin D status in South Korea.
PMID- 29952943
TI - Umbilicus-sparing laparoscopic versus open approach for treating symptomatic
urachal remnants in adults.
AB - The traditional surgical approach for removing a symptomatic urachal remnant is
via a lower midline laparotomy and infraumbilical incision or a laparoscopic
approach with umbilicoplasty. We reviewed our experience with umbilicus-sparing
laparoscopic urachal remnant excision in a single-center study and evaluated its
efficacy versus open approach (OA). This study was a retrospective study. Between
March 2012 and September 2016, 32 consecutive patients with symptomatic urachal
remnants underwent the umbilicus-sparing laparoscopic approach (USLA) (n = 17) or
OA (n = 15). The efficacy, recovery, and long-term outcomes were reviewed. Our
Results showed that the clinical characteristics of the patients in each group,
such as age, gender, body mass index (BMI), and disease type, had no significant
differences (P > .05). No significant difference was found in the surgical
procedure times (76.1 +/- 15.4 vs 69.2 +/- 13.9 minutes, P = .189) and
intraoperative blood loss (29.4 +/- 13.3 vs 32.2 +/- 12.9 mL, P = .543) between
the USLA groups and OA groups. However, the mean postoperative hospital stay
(patients with bladder cuff excision: 4.1 +/- 1.8 vs 6.1 +/- 1.4 days, P = .040
and patients without bladder cuff excision: 1.8 +/- 0.5 vs 3.6 +/- 0.8 days, P <
.001) and the time of full recovery (11.2 +/- 1.9 vs 15.6 +/- 3.1 days, P <
.001), the USLA group were both significantly shorter than that of the OA group.
No infected recurrence and malignant transformation had occurred at a mean follow
up of 32.4 +/- 8.1 and 34.1 +/- 8.8 months in USLA group and OA group,
respectively. In conclusion, to minimize the morbidity of radical excision,
umbilicus-sparing management of benign urachal remnants in adults is a safe and
efficacious alternative with superior cosmetic outcomes, postoperative recovery
compared with an OA or umbilicoplasty.
PMID- 29952944
TI - Clinical characteristics and prevalence of adrenal insufficiency in
hemodynamically stable patients with cirrhosis.
AB - It is well known that adrenal insufficiency is common in septic shock or
hemodynamically unstable patients. But, there is as yet no sufficient clinically
significant data about the exact prevalence or differences in the cause of
cirrhosis with adrenal insufficiency. To investigate adrenal insufficiency
prevalence in hemodynamically stable patients with cirrhosis and determine
differences based on cirrhosis severity or etiology.From July 2011 to December
2012, 69 hemodynamically stable patients with cirrhosis without infection
admitted at Hallym University Medical Center were enrolled. Adrenal insufficiency
was defined as a peak cortisol level < 18 MUg/dL, 30 or 60 minutes after 250 MUg
Synacthen injection.The study included 55 male patients (79.7%), and the mean age
was 57.9 +/- 12.9 years. Cirrhosis etiology was alcohol consumption, HBV, HCV,
both viral and alcohol related, and cryptogenic in 49, 15, 7, 11, 9 patients,
respectively. Adrenal insufficiency occurred in 24 patients (34.8%). No
differences were found in age, sex, mean arterial pressure, heart rate, HDL,
cirrhosis etiology, degree of alcohol consumption, encephalopathy, variceal
bleeding history, or hepatocellular carcinoma between patients with or without
adrenal insufficiency. Serum albumin level was lower (P < .05), and INR was
higher (P < .05) in patients with than in those without adrenal insufficiency.
However, multivariate analysis revealed no independent adrenal insufficiency
predictor. Significant negative correlations were found between Child-Pugh score
and peak cortisol levels (gamma=-0.365, P = .008).Adrenal insufficiency was
frequent even in hemodynamically stable patients with cirrhosis and tended to be
associated with only liver disease severity, being unrelated to cirrhosis
etiology.
PMID- 29952945
TI - Dehiscent high-riding jugular bulb presenting as conductive hearing loss: A case
report.
AB - RATIONALE: Jugular bulb anomalies are asymptomatic lesions commonly seen in
routine practice. However, some patients with jugular bulb anomalies may present
with symptoms such as tinnitus or conductive hearing loss (CHL). PATIENT
CONCERNS: A 9 year old boy complained right sided hearing disturbance without any
vestibular symptoms. Pure tone audiometry (PTA) revealed a mild right sided
conductive hearing loss. Otoscopy showed a red-purplish mass like lesion in his
right middle ear cavity, which was regarded as hypervascular tumor. DIAGNOSIS:
Based on otoscopic findings, preliminary differential diagnoses included jugular
bulb anomaly, hemotympanum, cholesterol granuloma and paraganglioma.
INTERVENTIONS: We performed contrast enhanced computed tomography of the temporal
bone (TBCT). OUTCOMES: CT scan showed and enhancing lesion which was bulging from
his right jugular foramen to the middle ear with dehiscent jugular bulb. The
lesion showed the same degree of contrast enhancement with the venous
vasculature. This lesion contacted with the tympanic membrane, incudostapedial
joint and round window, which might be attributable to interruption of sound
transmission mechanics. Otherwise there was no evidence of mass or trauma related
lesions in the temporal bone. LESSONS: Although most of jugular bulb anomalies
are asymptomatic, patients may present with conductive hearing loss due to the
interference of sound transmission mechanics.
PMID- 29952946
TI - Effectiveness of percutaneous neuromuscular electrical stimulation for neck pain
relief in patients with cervical spondylosis.
AB - BACKGROUND: This study aimed to evaluate the effectiveness and safety of
percutaneous neuromuscular electrical stimulation (PNMES) for treating neck pain
in patients with cervical spondylosis (CS). METHODS: One hundred and twenty four
patients with neck pain of CS were included, and then they were randomly divided
into a PNMES group and a control group in a ratio of 1:1. All patients received
PNMES or sham PNMES 30 minutes daily, 3 times weekly for 12 weeks. The primary
outcome was assessed by the visual analog scale (VAS). The secondary outcomes
were evaluated by the cervical range of motion (ROM), neck disability index (NDI)
score, as well as the adverse events (AEs). All outcome measurements were
measured at the end of 12-week treatment, and 4-week follow-up after treatment.
RESULTS: At the end of the 12-week treatment, and 4-week follow-up, the patients
receiving PNMES exhibited more decrease in the mean VAS (P < .01), and NDI (P <
.01) respectively, compared with the patients receiving sham PNMES. Additionally,
the increase in the mean ROM was also significantly higher in the PNMES group
than that in the sham PNMES group at the end of the 12-week treatment, and 4-week
follow-up, respectively (P < .01). No AEs were found in either group.
CONCLUSIONS: The results of this study demonstrated that PNMES is more effective
than Sham PNMES for neck pain relief in patients with CS.
PMID- 29952947
TI - Determinants of compassion satisfaction, compassion fatigue and burn out in
nursing: A correlative meta-analysis.
AB - BACKGROUND: Compassionate care is essential for better clinical and patient
outcomes, but during healthcare provision it can be compromised by several
factors. This study evaluates factors affecting compassion satisfaction,
compassion fatigue and burnout in nursing. METHODS: Literature search in
electronic databases was followed by data extraction, conversion, and meta
analyses under random effect model. Correlation coefficients (r) reported by
individual studies were first converted to z-scores for meta-analyses and the
overall effect sizes were then back-transformed into r. RESULTS: Eleven studies
(4054 respondents; 64.34 [95% confidence interval: 38.82, 89.86] % response rate;
age 39.81 [31.36, 48.27] years; 87.11 [79.48, 94.73] % females) were used for
meta-analysis. There was a strong positive correlation between compassion fatigue
and burnout (r = 0.59), whereas compassion satisfaction had weak negative
correlation with compassion fatigue (r = -0.226) but moderate with burnout (r =
0.446). Stress and negative affect were moderately positively associated with
compassion fatigue (r = 0.405) but weakly correlated with burnout (r = 0.119).
Positive affect and personal/social factors had weak inverse relationship with
burnout (r = -0.197). Positive affect also had a moderately positive relationship
with compassion satisfaction (r = 0.396). Demographic or professional factors
were not significantly related to compassion satisfaction, compassion fatigue, or
burnout. CONCLUSION: In nursing, a variety of stressful factors and negative
affect promote compassion fatigue and burnout whereas positive affect is helpful
in achieving compassion satisfaction.
PMID- 29952948
TI - A new 3D printed titanium metal trabecular bone reconstruction system for early
osteonecrosis of the femoral head.
AB - Presently, biomechanical support therapy for the femoral head has become an
important approach in the treatment of early osteonecrosis of the femoral head
(ONFH). Previous studies have reported that the titanium metal trabecular bone
reconstruction systems (TMTBRS) achieved satisfactory clinical results for the
treatment of early femoral head necrosis. Electron beam melting technology (EBMT)
is an important branch of 3D printing technology, which enables the construction
of an interface that is required for support of bone in-growth. However, the
effect of TMTBRS created using EBMT for clinical applications for early ONFH is
still unknown. At present, there are no reports on this topic worldwide. The
purpose of this study was to assess the safety of a new 3D printed TMTBRS implant
and to evaluate its clinical efficacy in early ONFH.Thirty patients who underwent
surgery for ONFH were selected. The stages of ONFH were classified according to
the Association Research Circulation Osseus (ARCO) classification. They were
followed-up and radiological examination was performed at 6, 12, and 24 months
post-surgery to assess TMTBRS stability and bone growth in the bone trabecular
holder portion surface. To evaluate hip function, postoperative Harris and Visual
Analogue Scale (VAS) scores were used.The postoperative Harris score increased
significantly and VAS score decreased significantly at the 12-month follow-up
compared to the 24-month follow-up, wherein the Harris score declined slightly
and the VAS score was slightly elevated with the aggravation of ONFH. With the
passage of time, postoperative improvement rates were 100% for IIA, 70% for IIB,
and 0% for IIC. Hip-preserving rates were 100% for IIA, 100% for IIB, and 50% for
IIC.The effect of TMTBRS treatment for early ONFH in ARCO IIA and ARCO IIB is
satisfactory. However, it is not recommended for a relatively large area of
necrosis such as in ARCO IIC.
PMID- 29952949
TI - Sclerosing angiomatoid nodular transformation of the accessory spleen: A case
report and review of literature.
AB - RATIONALE: Sclerosing angiomatoid nodular transformation (SANT) is a rare case
which usually occurs in spleen, but our case occurs in accessory spleen. PATIENT
CONCERNS: We reported a case of a 27 year old man who was identified with an
isodense mass in the left abdominal cavity by ultrasonicphysical examination
without symptoms. Blood routine and tumor markers (alpha fetal protein,
carcinoembryonic antigen, CA19-9, CA125) were normal. DIAGNOSES: The tumor was
firstly diagnosed as left abdominal mass and its origin was considered as small
intestinal by the radiologist. The pathological diagnosis was the sclerosing
angiomatoid nodular transformation (SANT) of the accessory spleen. INTERVENTIONS:
Laparoscopic splenectomy is a more reliable method for the treatment of SANT.
OUTCOMES: Non-enhanced CT showed iso-intensity lesion of the accessory spleen,
and enhanced CT showed progressive enhancement. According to the above
characteristics, we should consider the diagnosis of spleen SANT. We reviewed
some literatures to summarize the characteristics of SANT.
PMID- 29952950
TI - Kidney Transplantation from an extracorporeal membrane oxygenation-supported
brain-dead donor: A case report.
AB - RATIONALE: Extracorporeal membrane oxygenation (ECMO) can deliver effective
respiratory and circulatory maintenance to organ donors, improve organ function,
and shorten warm ischemic time before harvesting. However, ECMO-supported brain
dead donors (DBDs) still have a high risk of acute kidney injury related to
decreased renal oxygen delivery and inflammatory damage, which may cause early
graft failure. PATIENT CONCERNS: Kidney transplantation from an ECMO-supported
DBD. DIAGNOSES: We found an extremely abnormal "very dark blue" appearance of the
graft kidneys from an ECMO-supported DBD during kidney procurement.
INTERVENTIONS: Rather than discarding the graft kidneys, we performed an on-table
biopsy. Pretransplant biopsy results revealed minimal interstitial fibrosis in
the section of these graft kidneys. OUTCOMES: Two candidates received graft
kidneys, and the two grafts remained functional until the 8-month follow-up.
LESSONS: Currently, there is no standard method for evaluating graft kidney
function of ECMO-supported DBDs. Regardless of the donors' preoperative serum
creatinine (SCr) level, estimated glomerular filtration rate (eGFR), or gross
appearance of the graft kidney, we believe that it is more reliable to include
pretransplant biopsy as a criterion in clinical practice to safely accept kidneys
from ECMO-supported DBDs.
PMID- 29952951
TI - Quantitative evaluation of intravoxel incoherent motion diffusion-weighted
imaging (IVIM) for differential diagnosis and grading prediction of benign and
malignant breast lesions.
AB - BACKGROUND: That breast carcinoma is the most common malignant lesion in women.
This study aimed to differentiate benign from malignant breast lesions and to
predict grading of the latter by comparing the diagnostic value of different
parameters in intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI).
MATERIALS AND METHODS: Retrospective analysis was performed utilizing imaging and
pathological data from 112 patients with 124 breast lesions that underwent IVIM
DWI examination with 3.0 T MRI. Out of 124, 47 benign and 77 malignant lesions
were confirmed by pathological diagnosis. The diagnostic performance of f, D, and
D* value to distinguish benign from malignant breast lesions, was evaluated using
pathological results as the gold standard. Correlation between D value and Ki-67
index was evaluated to predict grading of malignant breast lesions. RESULTS: The
D value (0.99 +/- 0.21) of patients with malignant lesions was significantly
lower than that (1.34 +/- 0.18) of patients harboring benign lesions (P = .00).
The D* value (7.60 +/- 2.10) in malignant lesion group was higher than that (6.83
+/- 2.13) of the benign lesion group (P = .113). The f value (8.50 +/- 2.13) in
malignant lesion group was remarkably higher than that (7.68 +/- 1.98) of benign
lesion group (P = .035). For differential diagnosis of benign from malignant
breast lesions, optimal diagnostic threshold of D value and f value were 1.21 and
7.86, respectively. The areas of D and f values under the ROC curve were 0.883
and 0.601, respectively. The sensitivity, specificity, and accuracy of D value
were 83.0%, 86.7%, and 85.5%, respectively. Accordingly, those indexes of f value
were 64.9%, 57.4%, and 62.1%, respectively. Furthermore, the Ki-67 staining index
of malignant lesions was robustly negatively correlated with D value (r = -0.395,
P < .01). CONCLUSION: Concrete parameters of IVIM-DWI can help to improve the
specificity and accuracy in differential diagnosis of breast benign and malignant
lesions. D value is most relevant and valuable in predicting the grading of
malignant breast lesions.
PMID- 29952952
TI - Correlation between EML4-ALK, EGFR and clinicopathological features based on
IASLC/ATS/ERS classification of lung adenocarcinoma.
AB - To investigate the correlation between echinodermmicro tubule associated protein
like 4 (EML4)-anaplasticlymphomakinase (ALK), epidermal growth factor receptor
(EGFR) and clinicopathological features in patients diagnosed with lung
adenocarcinoma according to International Association for the Study of Lung
Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS)
international multidisciplinary classification of lung adenocarcinoma.Ninety
patients diagnosed with lung adenocarcinoma underwent surgical pathological
classification. Ventana immunohistochemical staining of the EML4-ALK was
performed. The mutation of EGFR and EML4-ALK was detected by real-time polymerase
chain reaction (RT-PCR) using the amplification refractory mutation system.The
positive rate of EML4-ALK mutation was calculated as 6.7% (6/90), dominantly
occurring in patients aged < 60 years. However, it was not correlated with the
gender, smoking history, maximal tumor diameter, pleural invasion, lymphatic
metastasis, or clinical staging. EML4-ALK fusion gene mutation was mainly
associated with the predominant subtypes of acinar and solid tumors with mucin
secretion. The mutation rate of EGFR was 60% (27/45). EGFR gene mutation mainly
occurred in the female, those with no smoking history and tumor size < 3 cm,
whereas it had no association with age, pleural invasion, lymphatic metastasis,
or clinical staging. It was histologically characterized with micropapillary,
lepidic, and papillary subtypes.The mutation rate of EML4-ALK is relatively high
in lung adenocarcinoma patients aged<60 years, pathologically characterized with
acinar and solid subtypes with mucin secretion. Female patients with no smoking
habit, tumor size<3 cm, pathologically characterized with micropapillary,
lepidic, and papillary subtypes had a high mutation rate of EGFR.
PMID- 29952953
TI - Anticoagulation efficacy of dabigatran etexilate for left atrial appendage
thrombus in patients with atrial fibrillation by transthoracic and
transesophageal echocardiography.
AB - To evaluate the anticoagulation efficacy of dabigatran etexilate for left atrial
appendage (LAA) thrombus resolution in patients with atrial fibrillation by
transthoracic echocardiography and transesophageal echocardiography, and to
investigate the anticoagulation factors.A total of 58 atrial fibrillation
patients with LAA thrombus in our hospital were enrolled. After dabigatran
etexilate anticoagulation for 3 months, the patients were divided into the
effective group and ineffective group according to dissolution of thrombosis. The
baseline data and the left atrial diameter (LAD), left atrial ejection fraction
(LAEF), left ventricular ejection fraction, LAA flow velocity (LAA-v), and LAA
thrombus size before and after anticoagulation treatment were recorded, and the
measurement index were statistically analyzed.After the patients received
anticoagulation treatment for 3 months, 15 patients had complete dissolution,
thrombus in 21 patients reduced significantly, and the complete dissolution rate
was 25.9% (15/58), the effective rate of dissolution was 62.1% (36/58). Compared
with the ineffective group, the proportion of persistent atrial fibrillation and
LAD in effective group were lower than those in the ineffective group, the LAEF
and LAA-v in the effective group were higher than those in the ineffective group,
and the differences were statistically significant (P < .05). Multivariate
logistic regression analysis on the baseline data and each ultrasound index
showed that the type of atrial fibrillation, LAD, LAEF, and LAA-v were
independently associated with the efficacy of anticoagulation (P <
.05).Dabigatran etexilate is effective in dissolution of LAA thrombus in patients
with atrial fibrillation, and the atrial fibrillation type, LAD, LAEF, and LAA-v
are significantly related with the efficacy of anticoagulation.
PMID- 29952954
TI - The outcomes and prognostic factors of the patients with unplanned intensive care
unit readmissions.
AB - This retrospective cohort study investigated the outcomes of patients with
unplanned intensive care unit (ICU) readmission.All of the patients readmitted to
ICU within 48 hours between 2010 and 2016 were enrolled.A total of 99 patients
early readmitted to ICU were identified and their mean age of the patients was
68.8 +/- 14.8 years. Respiratory failure was the most common cause of ICU
readmission (n = 48, 48.5%), followed by acute myocardial ischemia or worsening
heart failure (n = 25, 25.3%), sepsis (n = 22, 22.2%), gastrointestinal disease
(n = 16, 16.2%), and neurologic disease (n = 11, 11.1%). The median length of
stay in the ICU and hospital was 7 (IQR, 4-11.5) and 32 (IQR, 15.5-48.5) days,
respectively. A total of 34 patients died during the hospital stay and the rate
of in-hospital mortality was 34.3%. Patients with higher APACHE II scores
(adjusted odds ratio [OR], 1.17; 95% CI, 1.02-1.33), underlying malignancy
(adjusted OR, 4.70; 95% CI, 1.19-18.57), and cardiovascular organ dysfunction
(adjusted OR, 5.14; 95% CI, 1.24-21.38) were more likely to die.The mortality
rate of ICU readmission patients was high, especially for those with higher
APACHE II score, underlying malignancy and cardiovascular organ dysfunction.
PMID- 29952955
TI - Analysis of elasticity characteristics of ascending aorta, descending aorta and
pulmonary artery using 640 slice-volume CT.
AB - As the prevalence of coronary computed tomographic angiography (CCTA), it is
meaningful that CCTA can provide not only the structural details of artery, but
also functional information of vessel elasticity. Our aim was to explore the
elasticity characteristics of ascending aorta (AA), descending aorta (DA), main
pulmonary artery (MPA), left pulmonary artery (LPA), right pulmonary artery
(RPA), and their relationship between each other using 640 slice-volume computed
tomography (CT). Furthermore, this study will also observe their relations with
age.A total of 42 subjects that were free of cardiovascular disease, high blood
pressure, diabetes, and hyperlipidemia underwent CCTA on 640 slice-volume CT and
were enrolled in this study. The subjects were divided into 2 groups: Group 1,
age <46; Group 2, age >=46. The aortic distensibility (AD) and aortic compliance
(AC) of aorta and pulmonary artery (PA) of each group were compared.The AD and AC
of PA decreased in the following order: MPA, RPA, and LPA. The correlation
coefficients of different elastic parameters between different vessels were found
to be different. The correlation coefficient of AD between AA and DA, AA and MPA,
DA and MPA, RPA and MPA, LPA and MPA, and RPA and LPA were 0.689 (P = .000),
0.520 (P = .000), 0.393 (P = .010), 0.329 (P = .033), 0.579 (P = .000), and 0.534
(P = .000), respectively. The correlation coefficients of AC for the 6 groups
mentioned above were 0.351 (P = .023), 0.470 (P = .002), 0.249 (P = .112), 0.190
(P = .228), 0.441 (P = .005), and 0.409 (P = .010), respectively. There was an
age-dependent decrease of AD and AC in AA, DA, MPA, LPA (P < .05), but no
difference in RPA (P > .05).The elasticity characteristics of AA, DA, MPA, LPA,
and RPA could be well shown by 640 slice-volume CT. The elasticity relativity was
observed and was different between AA and DA, AA and MPA, LPA and MPA, LPA and
RPA. An obvious age-related decrease in vascular elasticity was found in AA, DA,
MPA, and LPA, which should be taken into consideration in clinical trials and
treatments for the elasticity-related cardiovascular diseases.
PMID- 29952956
TI - Comprehensive analysis of common safety profiles and their predictive factors in
520 records of liver cancer patients treated by drug-eluting beads transarterial
chemoembolization.
AB - This study aimed to investigate the difference of common adverse events (AEs)
between patients experienced first drug-eluting beads transarterial
chemoembolization (DEB-TACE; FD) and second or higher DEB-TACE (SHD), and the
factors influencing AEs.Five hundred twenty DEB-TACE records were retrospectively
reviewed in this cohort study, among which 284 and 236 records were in FD and SHD
groups, respectively. The incidence and/or severity of pain, fever, vomiting, and
increased blood pressure (BP) were collected.Pain numerical rating scale (NRS)
score, pain severity, body temperature, fever severity, and fever lasting days
were higher in FD group than in SHD group, while no difference of vomiting and
increased BP between 2 groups were disclosed. Age >=65 years was associated with
decreased high fever and less possibility of vomiting in FD group, and lower pain
and fever severity in SHD group; Male decreased the possibility of vomiting in
both the groups, and reduced increased BP incidence in SHD group; diabetes
history correlated with decreased pain degree and less fever in FD group.In
conclusion, SHD was better tolerated compared with FD in liver cancer patients,
and older age as well as male were correlated with less occurrence or severity of
common AEs in DEB-TACE operation.
PMID- 29952958
TI - Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio,
platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South
Korea.
AB - There is a growing interest in research aimed at better understanding the disease
status or predicting the prognosis of patients with simple blood tests associated
with systemic inflammation. The neutrophil-lymphocyte ratio (NLR), lymphocyte
monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and mean platelet volume
(MPV) can be used as factors to determine the prognosis of patients in various
clinical situations. However, reference values for these attributes based on
large, healthy populations have yet to be determined.From January 2014 to
December 2016, data from routine blood analyses were collected from healthy
patients in the checkup center of a tertiary hospital in Seoul, South Korea.
Retrospective data review was then performed on an electronic medical record
system. Data were treated anonymously as only age, sex, body mass index, medical
history including cancer diagnosis, medications, and smoking status were
considered. After the initial screen, we had a collection of 12,160 samples from
patients without any medical history, including cancer treatment. This patient
pool consisted of 6268 (51.5%, median age 47 years) and 5892 (48.5%, median age
46 years) male and female patients, respectively. The mean NLR across all ages
was 1.65 (0.79), and the values for men and women were 1.63 (0.76) and 1.66
(0.82), respectively. The mean LMR, PLR, and MPV were 5.31 (1.68), 132.40
(43.68), and 10.02 (0.79), respectively. This study provides preliminary
reference data on LMR, PLR, and MPV from different age and sex groups in South
Korea. The results suggest that different cutoff values should be applied to the
various patient populations.
PMID- 29952957
TI - Phosphorus-32 interstitial radiotherapy for recurrent craniopharyngioma:
Expressions of vascular endothelial growth factor and its receptor-2 and imaging
features of tumors are associated with tumor radiosensitivity.
AB - To investigate the relationship of the expression of vascular endothelial growth
factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR-2) and imaging
features with the therapeutic efficacy of Phosphorus-32 colloid interstitial
radiotherapy in recurrent craniopharyngioma.Thirty-two patients with recurrent
craniopharyngioma underwent phosphorus-32 colloid interstitial radiotherapy. The
tumor imaging features were classified into 4 types according to the thickness of
the cyst wall and signals of the cyst contents as shown by computed tomography
(CT) and magnetic resonance imaging (MRI) images. Protein expressions of VEGF and
VEGFR-2 in craniopharyngioma tissues were evaluated with immunohistochemistry
before radiotherapy. The tumor radiosensitivity was determined at 12 months after
the interstitial radiotherapy.VEGF mainly expressed in the tumor cytoplasm, and
VEGFR-2 expressed either in vascular endothelial cells or in tumor endothelial
cells. VEGF/VEGFR-2 expressions varied significantly in cases sensitive or
insensitive to the radiotherapy (VEGF: P = .028; VEGFR-2: P = .017). Tumor
imaging features were associated with the therapeutic efficacy of interstitial
radiotherapy (P = .000). VEGF expression had no association with the imaging
features of tumors (P = .226), but VEGFR-2 expression was associated with the
imaging features of tumors (P = .008).Our results confirmed the association among
imaging features, VEGFR-2 expressions, and tumor radiosensitivity in
craniopharyngiomas. Imaging features and VEGFR-2 expressions may add useful data
to the radiosensitive assessment of craniopharyngiomas.
PMID- 29952959
TI - The prognostic value of HOTAIR for predicting long-term prognosis of patients
with gastrointestinal cancers.
AB - BACKGROUND: Increased expression of HOX transcription antisense RNA (HOTAIR) has
been reported to be associated with unfavorable prognosis in cancer patients.
Several studies have evaluated the significance of HOTAIR in the development and
progression of gastrointestinal cancers (GICs). METHODS: Systematic literature
retrieval was performed by searching keywords in several electronic databases,
including PubMed, Embase, Web of Science, CNKI, Springer, Google Scholar, and
GEO. Relevant articles on association between HOTAIR expression levels and
prognosis in patients with GIC were collected and screened with eligible
criteria. The RevMan 5.2 software and Stata SE12.0 software was applied. RESULTS:
A total of 1297 patients from 15 eligible articles were included in this meta
analysis. The results revealed that increased expression of HOTAIR was
significantly associated with shorter overall survival (OS) in GIC patients
[hazard ratio (HR) = 1.93, 95% CI: 1.64-2.26], as well as poorer disease-free
survival (DFS) (HR = 2.79; 95% CI: 1.38-5.63). Additionally, the pooled odds
ratio (OR) indicated that increased HOTAIR was associated with
clinicopathological parameters, including lymph node metastasis (OR = 2.48, 95%
CI: 1.71-3.61), distant metastasis (OR = 4.34, 95% CI: 2.12-8.91), poor tumor
differentiation (OR = 2.90, 95% CI: 1.45-5.80), lymphovascular invasion (OR =
2.86, 95% CI: 1.83-4.46), high depth of tumor invasion (OR = 2.07, 95% CI: 1.36
3.16), and poor clinical stage (OR = 2.72, 95% CI: 1.70-4.35). In survival
analysis through the Kaplan-Meier plotter database, enhanced level of HOTAIR was
associated with better OS and DFS in gastric cancer patients. CONCLUSIONS: High
expression level of HOTAIR was related to poor clinical outcome of GIC patients.
The HOTAIR could be applied as potential biomarker for assessing the prognosis.
Further well-designed studies should be performed to verify the clinical
applications of HOTAIR in GIC.
PMID- 29952960
TI - Sustained clinical response after single course of rituximab as first-line
monotherapy in adult-onset asthma and periocular xanthogranulomas syndrome
associated with IgG4-related disease: A case report.
AB - RATIONALE: IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease
characterized by multi-organ involvement and variable clinical behavior. PATIENT
CONCERNS: We describe the case of a 50-year-old woman affected by a rare variant
of IgG4-RD, characterized by eyelid xanthelasmas, adult-onset asthma and salivary
and lacrimal glands enlargement. Multiple lymphadenopathies and a pulmonary mass
were present at initial evaluation. INTEVENTIONS: After a single course of
rituximab (2g in 2 refracted doses), an almost complete clinical remission was
achieved without chronic steroid administration. OUTCOMES: Magnetic resonance
imaging (MRI), high-resolution computed tomography (HRCT) of the thorax, and
positron emission tomography (18FDG-PET-CT) confirmed good response to treatment.
Circulating plasmablasts dropped to undetectable levels as well. Xanthelasmas
only remained unchanged. Remission persisted at 1-year follow-up. LESSONS:
Steroid therapy is still considered standard first-line therapy in IgG4-RD.
However, high doses are generally required and relapses are common during the
tapering phase. Rituximab is a well described steroid-sparing strategy, so far
reserved to refractory cases only. In our experience, rituximab has been used as
first-line monotherapy, showing great and sustained efficacy and optimal
tolerability. The peculiar variant of IgG4-RD affecting our patient, the
relatively low baseline plasmablast concentration, and the early placement of
rituximab therapy may have facilitated the good response.
PMID- 29952961
TI - A case report of successful pregnancy and delivery after peritoneal dialysis in a
patient misdiagnosed with primary infertility.
AB - RATIONALE: Currently, 15% of women in fertility age are infertile and the
frequency is increasing. Among the various causes of infertility, end-stage renal
disease (ESRD) has been shown to decrease the frequency of pregnancies compared
with normal females. However, dialysis of patients with ESRD increases the
likelihood of pregnancy.Herein, we report successful pregnancy and delivery after
peritoneal dialysis in a patient who was misdiagnosed as primary infertility.
PATIENT CONCERNS: A 37-year-old female who was unaware of her ESRD was
misdiagnosed with primary infertility. After undergoing artificial insemination,
she was referred to department of internal medicine because of generalized edema,
dyspnea, nausea, vomiting, and poor oral intake. After evaluation, she was
diagnosed with ESRD and initiated peritoneal dialysis. DIAGNOSES: The patients
was on peritoneal dialysis for a year and discovered that she was pregnant.
INTERVENTIONS: During pregnancy, the patient maintained a residual urine output,
BUN levels below 50 mg/dL, controlled blood pressure and a targeted hemoglobin
range. She obtained adequate calories and protein and was managed by a
multidisciplinary team. OUTCOMES: The patient delivered a preterm male baby with
no anomalies. LESSONS: ESRD should also be considered among the several causes of
infertility in fertile women. If ESRD is the cause of infertility, the frequency
of pregnancy increases following dialysis. If pregnancy is diagnosed early,
intensive renal replacement therapy, adequate nutritional intake and regular
fetal monitoring during pregnancy increase the chances of successful delivery
while maintaining PD.
PMID- 29952962
TI - Association between the PON1 Q192R polymorphism and coronary heart disease in
Chinese: A meta-analysis.
AB - BACKGROUND: The relation has not been reported consistently between the PON1
Q192R polymorphism and coronary heart disease (CHD). To clarify the discrepancy,
we performed the present meta-analysis to evaluate the association between the
PON1 gene Q192R polymorphism and CHD risk in Chinese population. METHODS: We
conducted a comprehensive search of the PubMed, EMBASE, and China National
Knowledge Infrastructure databases for all available case-control studies. Two
reviewers independently selected studies. Data were analyzed by STATA software
package v 12.0. RESULTS: Thirteen studies investigating the association between
the PON1 Q192R polymorphism and risk of CHD were selected in this meta-analysis
with 4353 cases and 4882 controls. The association between the PON1 Q192R
polymorphism and CHD is statistically significant under the recessive genetic
model (R/R vs Q/R + Q/Q, odds ratio [OR] = 1.111, 95% confidence interval [CI] =
1.017-1.214). We observed no statistical association between PON1 Q192R
polymorphism and risk of CHD under allele model (R vs Q, OR = 1.087, 95% CI =
0.976-1.209), homozygous model (RR vs QQ, OR = 1.192, 95% CI = 0.949-1.496), and
dominant genetic model (Q/R + R/R vs Q/Q, OR = 1.127, 95% CI = 0.938-1.354).
CONCLUSION: This meta-analysis suggests that the PON1 Q192R polymorphism has a
weak association with CHD risk in Chinese.
PMID- 29952963
TI - Behcet disease associated with gastrointestinal amyloidosis manifested as
hematochezia: A case report.
AB - RATIONALE: Behcet disease (BD) is an inflammatory disorder characterized by
recurrent oral aphthous ulcers, genital ulcers, ocular lesions, and skin lesions.
Complication of amyloidosis in patients with BD is rare. Here, we report a case
of BD with immunoglobulin light chain (AL)-amyloidosis manifested as
hematochezia. PATIENT CONCERNS: A 61-year-old man developed sudden hematochezia
due to bleeding from multiple small colonic ulcers; AL-amyloid deposition was
found on immunohistochemical examination of biopsy specimen of colonic ulcer.
Systemic investigation revealed cardiac disfunction with cardiomegaly and
progressive renal dysfunction, which indicated the presence of systemic AL
amyloidosis. DIAGNOSES: Based on the findings of colonic ulcers with cardiac and
renal involvement, a diagnosis of systemic AL-amyloidosis complicated by
incomplete BD was established. INTERVENTIONS: He was treated with increased dose
of oral prednisolone (20 mg/day), colchicine and mesalazine, because he was
reluctant to receive aggressive chemotherapy (melphalan and dexamethasone) or
autologous stem cell transplantation. OUTCOMES: Colonic ulcers completely
diminished after treatment, however, he died because of severe urinary tract
infection and progressive renal failure after one year of gastrointestinal (GI)
manifestations. LESSONS: Our case shows that patients with BD may have GI
manifestations due not only to entero-BD but also due to GI amyloidosis.
PMID- 29952964
TI - Port-site metastasis as a primary complication following diagnostic laparoscopy
of fallopian tube carcinoma: A case report.
AB - RATIONALE: Fallopian tube carcinoma is a rare female genital cancer with no
specific clinical and surgical features. It is hardly diagnosed on imaging due to
non-specific presentation. Laparoscopy has been recommended as the diagnostic
procedure for the assessment of suspicious ovarian and adnexal masses. However,
it has brought new complications like tumor recurrences at the trocar insertion
sites, called port-site metastasis (PSM). PATIENT CONCERNS: A 65-year-old,
postmenopausal woman presented to hospital with loss of appetite, Ultrasound
showed ill-defined pelvic mass. The patient was diagnosed with fallopian tube
carcinoma by a diagnostic laparoscopy. DIAGNOSES: The PSM as a primary
complication following diagnostic laparoscopy of fallopian tube carcinoma, which
is presumed by positron emission tomography/computed tomography and confirmed by
Nodule resection and further pathological assessment. INTERVENTIONS: As port-site
metastasis was suspected, the patient was advised to undergo umbilical mass
resection. OUTCOMES: the patient has no signs of recurrence was detected 20
months after the last surgery during follow-up. LESSIONS: Laparoscopy plays a
significant role in the diagnose and treatment of fallopian tubal and ovarian
malignancies but has a risk of PSM occurrence. When isolated PSM occurs the
management should be local resection.
PMID- 29952966
TI - CT texture analysis of histologically proven benign and malignant lung lesions.
AB - The purpose of our study was to determine accuracy of CT texture analysis (CTTA)
for differentiating benign from malignant pulmonary nodules, and well
differentiated from poorly differentiated lung cancers, with histology as the
standard of reference.In this IRB-approved study, 175 adult patients (average age
66 +/- 12 years; age range 27-89 years, male 82: female 93) who underwent a
noncontrast chest CT examination prior to CT-guided biopsy of pulmonary nodules
were included. There were 57 benign (24 tumors or tumor-like lesions; 33
inflammatory conditions) and 120 malignant (29 well-differentiated
adenocarcinomas, 48 poorly differentiated adenocarcinomas, and 43 squamous cell
carcinomas) diagnoses on pathology. CTTA was performed on the prebiopsy
noncontrast CT images using a commercially available software (TexRAD limited,
UK). The CTCA features analyzed included mean HU values, percent positive pixels
(PPP), mean value of positive pixels (MPP), standard deviation (SD), normalized
SD, skewness, kurtosis, and entropy.The ROC analyses showed that normalized SD
[AUC: 0.63, (CI: 0.55-72), P = .003] had moderate accuracy for differentiating
between benign and malignant lesions. For differentiating among well
differentiated and poorly differentiated tumors, the ROC analysis showed that
except skewness all other parameters were statistically significant The AUC
values of other CTTA parameters were: mean (AUC: 0.73-0.76, P = .001- < .0001).CT
texture analyses can reliably predict well- and poorly differentiated lung
malignancies. However, inflammatory lung lesions with tissue heterogeneity
negatively affect the performance of CTTA when it comes to differentiation
between benign and malignant pulmonary nodules.
PMID- 29952965
TI - A UK-based pilot study of current surgical practice and implant preferences in
lumbar fusion surgery.
AB - Lumbar fusion surgery is an established procedure for the treatment of low back
pain. Despite the wide set of alternative fusion techniques and existing devices,
uniform guidelines are not available yet and common surgical trends are scarcely
investigated.The purpose of this UK-based study was to provide a descriptive
portrait of current surgeons' practice and implant preferences in lumbar fusion
surgery.A UK-based in-person survey was designed for this study and submitted to
a group of consultant spinal surgeons (n = 32). Fifteeen queries were addressed
based on different aspects of surgeons' practice: lumbar fusion techniques,
implant preferences, and bone grafting procedures. Answers were analyzed by means
of descriptive statistics.Thirty-two consultant spinal surgeons completed the
survey. There was clear consistency on the relevance of a patient-centered
management (82.3%), along with a considerable variability of practice on the
preferred fusion approach. Fixation surgery was found to be largely adopted
(96.0%) and favored over stand-alone cages. With regards to the materials,
titanium cages were the most used (54.3%). The geometry of the implants
influenced the choice of lumbar cages (81.3%). Specifically, parallel-shape cages
were mostly avoided (89.2%) and hyperlordotic cages were preferred at the lower
lumbar levels. However, there was no design for lumbar cages which was
consistently favored. Autograft bone graft surgeries were the most common
(60.0%). Amongst the synthetic options, hydroxyapatite-based bone graft
substitutes (76.7%) in injectable paste form (80.8%) were preferred.Current
lumbar fusion practice is variable and patient-oriented. Findings from this study
highlight the need for large-scale investigative surveys and clinical studies
aimed to set specific guidelines for certain pathologies or patient categories.
PMID- 29952967
TI - Profiling of lung microbiota in the patients with obstructive sleep apnea.
AB - Lung microbiota may affect innate immunity and treatment consequence in the
obstructive sleep apnea (OSA) patients. Bronchoalveolar lavage fluid (BALF) was
obtained from 11 OSA patients and 8 patients with other lung diseases as control,
and used for lung microbiota profiling by PCR amplification and sequencing of the
microbial samples. It was demonstrated that phyla of Firmicutes, Fusobacteria,
and Bacteriodetes were relatively abundant in the lung microbiota. Alpha
diversity comparison between OSA and control group revealed that Proteobacteria
and Fusobacteria were significantly higher in OSA patients (0.3863 +/- 0.0631 and
0.0682 +/- 0.0159, respectively) than that in control group (0.119 +/- 0.074 and
0.0006 +/- 0.0187, respectively, P < .05 for both phyla). In contrast, Firmicutes
was significantly less in OSA patients (0.1371 +/- 0.0394) compared with that in
the control group (0.384 +/- 0.046, P < .05). Comparison within a group (beta
diversity) indicated that the top 5 phyla in the OSA lung were Proteobacteria,
Bacteroidetes, Firmicutes, Fusobacteria, and Acidobacteria, while the top 5 phyla
in the control group were Firmicutes, Bacteroidetes, Proteobacteria,
Actinobacteria, and Acidobacteria. These findings indicated that lung microbiota
in OSA is distinct from that of non-OSA patients. Manipulation of the microbiota
may be an alternative strategy to augment airway immunity and to reduce
susceptibility to airway infection.
PMID- 29952968
TI - Evaluation of computed tomography vascular reconstruction for the localization
diagnosis of perigastric mass.
AB - BACKGROUND: The aim of this study was to evaluate the utility of computed
tomography (CT) vascular reconstruction in the localization diagnosis of
perigastric mass. METHODS: Fifty-eight patients with pathologically detected
perigastric mass underwent abdominal dynamic contrast-enhanced CT. CT vascular
reconstructions were produced from arterial phase data using volume rendering
(VR), multiplanar reconstruction (MPR), and maximal intensity projection (MIP).
Image analysis was focused on the relationship between the mass, perigastric
arteries, and the gastric wall. Localization diagnosis values were compared
between CT vascular reconstruction and dynamic-enhanced CT images. RESULTS: Among
the 58 cases of perigastric mass, 41 cases originated from the stomach, 7 cases
from the left liver lobe, 6 from the pancreas, 2 from lessor omental bursa, 1
from transverse mesocolon, and 1 from left adrenal gland. The accuracy of CT
vascular reconstruction images in the localization diagnosis of perigastric mass
was higher than that of dynamic-enhanced CT images (98.3% and 86.2%,
respectively, P = .04). On the reference level, 35 (35/41) patients with stomach
originated masses showed the mass adjacent perigastric arteries pushed away from
the stomach (arterial displacement sign), and 15 (15/17) patients with nonstomach
originated masses showed perigastric arteries between the mass and the stomach
(arterial entrapment sign). The sensitivity, specificity, positive predictive
value, and negative predictive value of the localization diagnosis of perigastric
mass with arterial displacement sign were 85.4%, 100%, 100%, and 73.9%,
respectively, and with arterial entrapment sign, 88.2%, 100%, 100%, and 95.3%,
respectively. CONCLUSION: CT vascular reconstruction can clearly depict the
relationship between perigastric mass and adjacent perigastric arteries, which
may help us more accurately differentiate between stomach-originated and
nonstomach-originated masses compared with original dynamic-enhanced CT images.
PMID- 29952969
TI - Anticoagulation treatment of portal vein thrombosis in a patient with cirrhosis
awaiting liver transplantation: A case report.
AB - RATIONALE: Portal vein thrombosis (PVT) is relatively common in patients with
liver cirrhosis waiting for liver transplantation (LT). Anticoagulation is an
important non-invasive treatment strategy for patients with cirrhosis and PVT.
PATIENT CONCERNS: This is the case of a 51-year-old man who presented with
cryptogenic liver cirrhosis associated with ascites. Computed tomography (CT) and
Doppler ultrasonography (US) showed a partially obstructive thrombus of the
portal vein (Yerdel Grade II). DIAGNOSIS: Portal vein thrombosis (Yerdel Grade
II); liver cirrhosis. INTERVENTIONS: The PVT was completely recanalized after 4
months of treatment with the low molecular weight heparin (LMWH) medication
enoxaparin but discontinuation of anticoagulants led to PVT recurrence. The
patient's condition deteriorated, even though re-treating the anticoagulation
with enoxaparin significantly reduced the PVT. OUTCOMES: The thrombus was removed
by a thrombectomy and LT was performed successfully without any vascular
complications. LESSONS: Patients with cirrhosis and PVT who are waiting LT can be
effectively treated with LMWH anticoagulants. Careful use of anticoagulation is
generally safe. Early initiation of anticoagulation treatment may be associated
with a high rate of portal vein recanalization.
PMID- 29952970
TI - Neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase, lipase, high-density
lipoprotein as a panel of factors to predict acute pancreatitis in pregnancy.
AB - Acute pancreatitis in pregnancy (APIP) is a rare but dangerous complication. APIP
has common symptoms with acute abdomen. Assessment of an acute abdomen is more
complicated during pregnancy because the gravid uterus could mask most of
symptomatic signs. It has been a challenge to diagnose APIP by physical
examination or diagnostic imaging. Case studies on APIP are also limited for
analysis on the risk factors associated with the disease. This retrospective
study evaluated a series of risk factors from a relatively substantial number of
APIP cases to determine early predictors or prognosis markers for APIP.Fifty-nine
APIP patients together with 179 random normal pregnant women in Shengjing
Affiliated Hospital of China Medical University were included for this
retrospective study. Medical parameters of blood test in biochemistry and
hematology were compared between 2 groups using t test. Multivariate logistic
regression analysis was performed to investigate the relationship between various
factors and APIP using Statistical Applied Software (SAS student
version).Compared with normal pregnant women, APIP patients have elevated values
in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea
nitrogen, creatinine, C-reactive protein, direct bilirubin, fibrin degradation
products, gamma-glutamyl transpeptidase (GGT), glucose, lipase, pH and decreased
values in albumin, fibrinogen, high-density lipoprotein (HDL), hemoglobin, low
density lipoprotein cholesterol (LDL-D), and total proteins from their blood
tests. In addition, APIP patients have decreased numbers in red cells but
increased numbers in white blood cells and increased ratio of
neutrophil/lymphocyte (N/L). Among these factors, N/LR, GGT, lipase, and HDL are
significantly associated with APIP. This study suggests that the combination of
those factors serve as a panel of indicators for early-onset prognosis of
APIP.GGT, lipase, HDL, and N/LR can serve as a panel of factors to predict APIP.
More case studies are important to further evaluate the predicting power of this
panel factors in APIP.
PMID- 29952971
TI - Discrimination of pyogenic spondylitis from brucellar spondylitis on MRI.
AB - Retrospective Cross-Sectional Study.The purpose of this study was to investigate
the accuracy of magnetic resonance imaging (MRI) for distinguishing between
pyogenic spondylitis and brucellar spondylitis.Although pyogenic spondylodiscitis
(PS) and brucellar spondylitis (BS) are common causes of spinal infections, the
variety of their clinical manifestations complicates differential diagnosis. MRI
may be helpful in differential diagnosis and treatment.MRI images of 64 patients
who underwent MRI of the spine and with confirmed spondylitis were
retrospectively reviewed. After referring to the related medical literature, we
compared 32 patients with pyogenic spondylitis and 32 patients with brucellar
spondylitis regarding MRI findings. Statistical analysis was performed with the
chi-square test. Statistical significance was defined as P < .05.The significant
differences between PS and BS on MRI findings are listed as follows (P < .05):
diffuse, partial and fan-shaped hyperintense signals on middle sagittal fat
suppressed weighted images (PS: 51, 11, 3/65 vs BS:35, 18, 19/72); focal endplate
destruction (PS: 9/43 vs BS:27/35); extensive end plate destruction (PS: 29/43 vs
BS:8/35); ballooning change of the intravertebral space (PS: 7/32 vs BS:0/32); an
inflammatory reaction line from the end plate (PS: 30/65 vs BS: 1/72); a disc
invasion sign (PS: 1/28 vs BS:12/33); an inflammatory reaction line in the disc
(PS: 5/28 vs BS:25/33); and 8) severe intravertebral space destruction (PS: 17/28
vs BS:12/33);MRI imaging provides useful information for the differentiation
between pyogenic spondylitis and brucellar spondylitis.
PMID- 29952972
TI - Effects of arterial blood on the venous blood vessel wall and differences in
percentages of lymphocytes and neutrophils between arterial and venous blood.
AB - Vascular sclerosis mostly occurs in arteries and is mainly related to anatomic
structure and hemodynamics of artery. This study aimed to investigate effects of
arterial blood on vein wall and explore differences of composition between
arterial and venous blood.Ultrasound was used to examine the distal venous
structure of arteriovenous fistula in uremia patients. Immunohistochemistry was
used to study the pathology of the distal vein. Twelve patients were divided into
control group and trial group. Patients received an arteriovenous fistula within
1 month in control group. Patients had undergone this surgery >=2 years before in
the trial group. Blood samples were collected from the aortic, arterial, and
venous vessels of 51 patients who had taken coronary angiography and analyzed
with blood routine rest, biochemical, and immunological measures to compare the
differences of blood composition between artery and vein. This study was
registered with the China Clinical Trial Center website under registration number
ChiCTR-OOC-16008085.In the trial group, the vascular wall of distal veins of
fistula were thickened and hardened. No significant differences of blood
composition were found between the aortic and radial arterial blood. However, the
differences in the percentages of lymphocytes and neutrophils between arterial
and venous blood were significant (Pa = .0095, Pb = .01).Under smooth hemodynamic
conditions, arterial blood caused hardening of the venous wall. Arterial and
venous blood differed in the percentage of lymphocyte and neutrophils. This may
contribute to the vascular sclerosis that is observed in arteries more often than
veins.
PMID- 29952973
TI - Ticagrelor-induced thrombotic thrombocytopenic purpura: A case report and review
of the literature.
AB - RATIONALE: Ticagrelor, a new type of P2Y12 receptor antagonist, has been highly
recommended to be used in acute coronary syndrome by the latest guideline, but
its side effects are not well-known. We seek to illustrate a potential fatal
condition, thrombotic thrombocytopenic purpura (TTP), caused by ticagrelor.
PATIENT CONCERNS: An 87-year-old man who had been prescribed with ticagrelor for
2 months after ST-elevation myocardial infarction (STEMI), presented with severe
thrombocytopenia, anemia, renal and liver dysfunction, heart failure and fever.
DIAGNOSES: Peripheral blood smear showed schistocytosis, and a disintegrin and
metalloproteinase with thrombospondin motifs 13 (ADAMTS13) activity is low, with
normal initial coagulation tests, which were compatible with a diagnosis of TTP.
INTERVENTIONS: After cessation of ticagrelor and initiation of therapeutic plasma
exchange, our patient recovered. OUTCOMES: Re-administration of ticagrelor
aggravated TTP and led the patient to death. LESSONS: Clinicians should be aware
of the possibility of ticagrelor-induced TTP in patients with a history of recent
myocardial infarction; It is of crucial significance to discontinue and never
reuse ticagrelor as long as it is suspected to be implicated in TTP.
PMID- 29952974
TI - Robot-assisted laparoscopic surgery for abdominal metastatic melanoma mimicking a
gastrointestinal stromal tumor: A case report and review of the literature.
AB - RATIONALE: Uveal melanoma is the most common primary intraocular malignancy,
which could metastasize at an early stage of the disease and associated with poor
prognoses. Liver, small bowel, stomach, and colon are the most common locations
for metastatic visceral melanoma, however, solitary abdominal metastasis from
uveal melanoma is extremely rare. PATIENT CONCERNS: The current study reports the
case of a 33-year-old man with history of treated choroidal melanoma of the left
eye that developed metastasis to the abdomen, preoperative endoscopic
ultrasonography and computed tomography strongly suggested as a gastrointestinal
stromal tumor (GIST). DIAGNOSES: The patient was diagnosed with abdominal
metastatic melanoma according to his medical history and histopathological
results. INTERVENTIONS: The young adult underwent robot-assisted laparoscopic
surgery. OUTCOMES: The patient finally got the definite diagnosis with his
medical history and histopathological results and he has been living disease free
for nearly 3 years after the surgery. LESSONS: Although rare, the possibility of
abdominal metastatic melanoma presenting with the clinical picture of
gastrointestinal stromal tumor must be always considered by the surgeon
especially the patients with a history of primary malignant melanoma.
PMID- 29952975
TI - A case report: Splenic abscess caused by Burkholderia pseudomallei.
AB - RATIONALE: Melioidosis is an emerging infectious disease caused by Burkholderia
pseudomallei. To our knowledge, there have been very few cases of splenic
abscesses due to melioidosis in Hainan, China. PATIENT CONCERNS: The patient was
a 55-year-old male farmer, who was admitted in our hospital with persistent left
epigastric dull pain accompanied by chills and febrile. One month before, the
patient presented with persistent abdominal pain. After received anti-infection
therapy, the subjective symptoms eased slightly, but recently he suffered from
intermittent abdominal pain again. DIAGNOSES: Bacteria isolated from splenic pus
were identified as B. pseudomallei by the Phoenix-100 system and indirect
immunofluorescence. INTERVENTIONS: The patient was treated by surgical excision
and anti-infection therapy. OUTCOMES: The patient was then treated with
intravenous ceftazidime and oral trimethoprim-sulfamethoxazole for 2 weeks and
his clinical symptoms improved. LESSONS: In endemic areas, B. pseudomallei should
be considered as a causative organism of splenic abscess in patients with
established risk factors. The isolation of B. pseudomallei from abscess sites is
crucial to improve clinical outcomes by appropriate antimicrobial therapy coupled
with surgical drainage.
PMID- 29952976
TI - The prognostic value of microRNA-183 in human cancers: A meta-analysis.
AB - BACKGROUND: Several studies have been conducted to explore the prognostic value
of miR-183 in different types of cancer; however, their results were
controversial. Therefore, the present meta-analysis was conducted to
comprehensively evaluate the prognostic value of miR-183 expression level in
cancer. METHODS: A comprehensive literature search was carried out by searching
PubMed and EMBASE database between January 1966 and April 2017. Fixed effect and
random effect models were used to evaluate the pooled hazard risk (HR) and the
relevant 95% confidence intervals (CIs). Subgroup analyses and sensitivity
analysis were also carried out. RESULTS: A total of 12 studies published between
2011 and 2017 were included in the present meta-analysis. The meta-analysis
result indicated that there was a significant association between miR-183
expression level and overall survival (HR = 2.642; 95%CI: 2.152-3.245), and there
was a significant association between miR-183 expression level and tumor
progression (HR = 2.403; 95%CI: 1.267-4.559). In subgroup analysis, we found that
high expression level was significantly associated with poor prognosis in most
cancers (HR = 2.824, 95%CI: 2.092-3.813); however, low miR-183 level was
significantly associated with poor prognosis in melanoma and pancreatic ductal
adenocarcinoma (HR = 2.322, 95%CI: 1.337-4.031). CONCLUSIONS: The results of our
meta-analysis indicated that the highly expressed miR-183 might predict poor
survival of patients with most cancer types, whereas the downregulated miR-183
level might be associated with poor prognosis in patients with melanoma and
pancreatic ductal adenocarcinoma.
PMID- 29952977
TI - Successful management of multiple-systemic Langerhans cell histiocytosis
involving endocrine organs in an adult: A case report and review of literature.
AB - RATIONALE: Langerhans cell histiocytosis (LCH) involving non-endocrine organs has
been frequently reported, whereas LCH involving endocrine organs is rare and the
mechanism is unclear. PATIENT CONCERNS: We report a case of multiple-systemic
Langerhans cell histiocytosis (LCH) that first manifested with thyroid goiter,
followed by pituitary and liver involvement. DIAGNOSES: The diagnosis was
confirmed based on immunohistochemistry of the thyroid and liver. INTERVENTIONS:
The patient was treated with thyroidectomy combined with chemotherapy and
radiation therapy for thyroid and liver, respectively. OUTCOMES: Surprisingly,
the patient presented with clinical remission and no new lesion of LCH was found
during follow-up over 10 years. LESSONS: LCH involving the endocrine system is
unusual and easily misdiagnosed or delayed, especially when the thyroid and
pituitary glands are involved. Pathological examination is necessary for a
definitive diagnosis. Regular examinations, such as anterior and posterior
pituitary hormones, should be especially evaluated annually in the patients with
LCH involving endocrine system.
PMID- 29952978
TI - Body mass index and prognosis of breast cancer: An analysis by menstruation
status when breast cancer diagnosis.
AB - OBJECTIVE: To examine whether obesity/overweight is a risk predictor for breast
cancer recurrence and death by menopausal status in a retrospective study.
METHODS: We performed a retrospective analysis of 1017 breast cancer patients
treated in our hospital from January 2004 to December 2012. Three groups were
divided according to body mass index (BMI) when breast cancer diagnosis: normal
weight, BMI < 25.0 kg/m; overweight, 25.0<=BMI < 30.0 kg/m; and obesity,
BMI>=30.0 kg/m. The clinicopathological characteristics and clinical outcomes of
patients within 5 years following breast cancer diagnosed were analyzed. Subgroup
analyses of BMI on breast cancer prognosis were analyzed according to the
menopausal status when breast cancer diagnosis. The Cox proportional hazards
model was used to estimate hazard ratios (HRs) and 95% confidence intervals
(CIs). RESULTS: Overweight and obesity groups were associated with larger size
tumors, older age, increased proportion of postmenopausal patients and less
patients choosing anthracycline and/or taxane regimen. The 5-year disease-free
survival (DFS) and overall survival (OS) decreased in overweight and obese
patients (P < .001), and both overweight and obesity were independent predictors
for increased risks of breast cancer relapse and death (P < .001). When
stratified by menopausal status, both overweight and obesity were associated with
reduced 5-year DFS and OS in postmenopausal patients (P < .050), and multivariate
analysis showed that the risk of relapse and breast cancer mortality in these 2
groups also increased (P < .050). Among premenopausal patients, the risks of
relapse and death were significantly increased in obesity group rather than
overweight group by multivariate analysis. CONCLUSION: Overweight and obesity
might be independently associated with poorer prognosis for breast cancer
patients, and the effects of overweight on the breast cancer prognosis seem to be
related to menopausal status.
PMID- 29952979
TI - Small cell variant of ALK-positive anaplastic large cell lymphoma with primary
subcutaneous presentation: A case report.
AB - RATIONALE: The rare morphological variant of anaplastic large cell lymphoma
(ALCL) may pose a challenge in diagnosis, especially when presentation primarily
involves skin lesions. PATIENT CONCERNS: Here we describe a rare case of small
cell variant of ALCL in an 11-year-old girl. DIAGNOSIS: We performed clinical,
morphological, and immunohistochemical analyses of developed cutaneous nodules.
INTERVENTIONS: Pathologists should consider this small cell variant in ALCL
differential diagnosis, as early and correct diagnosis has important clinical
implications. OUTCOMES: Allogeneic hematopoietic stem cell transplantation
appears to be a promising treatment option for small cell variant of ALCL.
LESSONS: Histological diagnosis of small cell variant of ALCL is challenging
among pediatricians because of its low incidence and atypical presentation. We
provide a short review of the small cell variant of ALCL to facilitate the
diagnosis of this difficult-to-recognize entity.
PMID- 29952980
TI - Is dry needling effective for low back pain?: A systematic review and PRISMA
compliant meta-analysis.
AB - BACKGROUND: To evaluate the efficacy and safety of dry needling (DN) for treating
low back pain (LBP). METHODS: Nine databases were searched from inception to
October 2017. Eligible randomized controlled trials (RCTs) involving DN for
treating LBP were retrieved. Two reviewers independently screened the articles,
extracted data, and evaluated the risk of bias among the included studies using
the risk of bias assessment tool by Cochrane Collaboration. RESULTS: Sixteen RCTs
were included and the risk of bias assessment of them was "high" or "unclear" for
most domains. Meta-analysis results suggested that DN was more effective than
acupuncture in alleviating pain intensity and functional disability at
postintervention, while its efficacy on pain and disability at follow-up was only
equal to acupuncture. Besides, DN was superior to sham needling for alleviating
pain intensity at postintervention/follow-up and functional disability at
postintervention. Additionally, qualitative review revealed that DN combined with
acupuncture had more significant effect on alleviating pain intensity at
postintervention and achieved higher response rate than DN alone. However,
compared with other treatments (laser, physical therapy, other combined
treatments, etc.), it remained uncertain whether the efficacy of DN was superior
or equal because the results of included studies were mixed. CONCLUSIONS:
Compared with acupuncture and sham needling, DN is more effective for alleviating
pain and disability at postintervention in LBP, while its effectiveness on pain
and disability at follow-up was equal to acupuncture. Besides, it remains
uncertain whether the efficacy of DN is superior to other treatments.
Nevertheless, considering the overall "high" or "unclear" risk of bias of
studies, all current evidence is not robust to draw a firm conclusion regarding
the efficacy and safety of DN for LBP. Future RCTs with rigorous methodologies
are required to confirm our findings. DETAILS OF ETHICS APPROVAL: No ethical
approval was required for this systematic review and meta-analysis.
PMID- 29952981
TI - Clinically simplified screening methods to evaluate maximum standard uptake value
from F-18-FDG-PET/CT in patients with non-small-cell lung cancer.
AB - Maximum standard uptake value (SUVmax) of F-18-fluorodeoxyglucose positron
emission tomography-computed tomography (FDG-PET/CT) is reportedly useful for
evaluating regional lymph nodes (RLNs) of non-small-cell lung cancer (NSCLC) to
predict malignancy. However, it is difficult for clinicians to measure SUVmax
(mSUVmax) as calculated by a workstation.We assessed the utility of simplified
SUVmax (sSUVmax) in screening RLNs for pathologic malignancy. The highest color
was visually defined in the region of interest. The resulting color can be
quantified using the color bar, and interpreted as sSUVmax. Patients in
respiratory medicine and surgery who underwent both contrast-enhanced CT and FDG
PET/CT within 3 months before radical lobectomy were evaluated retrospectively.
The correlation was examined by regression analysis and receiver operating
characteristic (ROC) curve analyses.Participants comprised 69 patients with NSCLC
treated between May 2009 and April 2016. Medical group comprised 22 patients from
respiratory medicine. The prediction model could be written as a linear
relationship (mSUVmax = 1.019 * sSUVmax; R = 0.930). A total of 316 RLNs resected
by surgery in total cohort were pathologically determined. From ROC curves, area
under curve for sSUVmax was 0.72 (95% confidence interval, 0.61-0.83; P < .0002).
The cutoff sSUVmax was 2.42 (sensitivity, 52%; specificity, 88%; accuracy,
85%).The sSUVmax allows quantification of colors from FDG-PET/CT and shows a
close correlation to mSUVmax. This value may have potential in screening for
RLNs, and thoracic clinicians can readily determine the value. These findings may
facilitate better planning of therapeutic strategy in the real world.
PMID- 29952982
TI - Cross-cultural adaptation and validation of the Chinese version of the shoulder
pain and disability index in patients with symptomatic shoulder pain: A
prospective case series.
AB - : The aim of this study is to cross-culturally adapt and translate the original
version of SPADI into Chinese (C-SPADI), and to test the reliability, validity,
and responsiveness of the C-SPADI.This research was a test of previously
developed diagnostic criteria in a series of consecutive patients with
universally applied gold standard. The original version was translated into
Chinese according to international recognized standards. Patients who were
diagnosed with a shoulder disorder and underwent shoulder arthroscopic treatments
from 2014 to 2015 were enrolled in our study. Each participant was asked to
finish the C-SPADI, the Short-Form 36 (SF-36), and the Oxford Shoulder score
(OSS) at first visit. The C-SPADI was completed a second time with an interval of
7 days. Six months after arthroscopic treatments, the C-SPADI was completed a
third time for responsiveness evaluation. The Cronbach alpha, intraclass
correlation coefficient (ICC), standard error of measurement (SEM), minimally
detectable change (MDC), Pearson correlation coefficient (r), effect size (ES),
and standardized response mean (SRM) were calculated to evaluate the reliability,
validity, and responsiveness of C-SPADI respectively.The original version of the
SPADI was well adapted and translated into Chinese. The Cronbach alpha ranged
from 0.812 to 0.912 in all subscales and total scale of the C-SPADI, indicating
good or excellent internal consistency. The test-retest reliability (ICC = 0.887
0.915, SEM = 5.47, MDC = 15.16) was proved to be good or excellent. Moderate or
good correlations (r = 0.556-0.672) were obtained between the C-SPADI and the
OSS, physical subscales of SF-36; and poor, fair, or moderate correlations (r =
0.038-0.492) were obtained between the C-SPADI and mental subscales of SF-36,
which, adequately illustrated good discriminant validity in the C-SPADI.
Additionally, the responsiveness was considered good in the C-SPADI (SRM = 1.58
2.44, ES = 1.79-2.17).The C-SPADI was documented to be a reliable, valid, and
responsible instrument for self-assessment of patients with shoulder disorders in
China. LEVEL OF EVIDENCE: Level II.
PMID- 29952983
TI - The co-existence of Lemierre's syndrome and Bezold's abscesses due to
Streptococcus constellatus: A case report.
AB - RATIONALE: The ancient infectious diseases, Lemierre's Syndrome and Bezold's
Abscesses are rare. PATIENT CONCERNS: A 70-year-old Japanese woman with a 15-year
history of Parkinson's disease was referred to our hospital due to fever,
occipital headache and bilateral shoulder pain that had continued for three
months. She had been prescribed prednisolone due to a diagnosis of polymyalgia
rheumatica. DIAGNOSES: A blood culture revealed bacteremia of Streptococcus
constellatus. In addition, computed tomography revealed Bezold's abscesses and
Lemierre's syndrome. INTERVENTIONS: We administered ceftriaxone for 31 days,
followed by oral amoxicillin. OUTCOMES: The patient recovered and the abscesses
improved. LESSONS: This case underscores the importance of blood culture tests
and cross-referencing with radiological imagings in the diagnoses of these rare
critical infectious diseases that mimic polymyalgia rheumatica.
PMID- 29952984
TI - Impaired retinal pigment epithelium in paclitaxel-induced macular edema: A case
report.
AB - RATIONALE: Cystoid macular edema (CME) is a rare complication of the paclitaxel.
However, the pathophysiology was unknown. PATIENT CONCERNS: A 60-year-old female
presented with bilateral blurred vision due to cystoid macular edema after taking
12-course paclitaxel for her breast cancer. Optical coherence tomography (OCT),
fluorescein angiography (FAG), indocyanine green angiography (ICGA),
electroretinogram (ERG) and electrooculogram (EOG) were performed. DIAGNOSES:
Paclitaxel-induced macular edema. INTERVENTIONS: Paclitaxel was discontinued and
supportive treatment with pentoxifylline was given. OUTCOMES: The OCT showed
bilateral cystoid macular edema. Impaired filling of choriocapillaries was noted
on the ICGA; while EOG revealed decreased Arden ratio. The visual acuity, cystoid
macular edema and decreased Arden ratio improved slowly over six months. LESSONS:
Paclitaxel rarely causes cystoid macular edema. The damage of choriocapillaries
and retinal pigment epithelium might be the underlying cause. Immediate
discontinuation of the drug helps visual recovery.
PMID- 29952985
TI - Early diagnosis and successful treatment of acquired toxoplasmosis infectious
retinochoroiditis: A case report.
AB - RATIONALE: Toxoplasma gondii is distributed worldwide, infecting a large
population. It can cause focal necrotic retinitis or retinochoroiditis in the
human eyes and is one of the most common causes of posterior uveitis. PATIENT
CONCERNS: A 68-year-old patient with normal immunity was complained about blurred
vision and black shadow in the right eye for 1 week. DIAGNOSES: Combined Yellow
and-white bulged lesions in the fundus of the right eye with the Goldmann-Witmer
coefficient = 2 and based on the serological indicators, we considered the
diagnosis of T. gondii infection-induced retinochondritis. INTERVENTIONS:
Acetylspiramycin 0.4 QID * 3 weeks, concussive 20 days treatment after 3 days,
for a total of 3 months, prednisone 20 mg/day with a weekly reduction of 5 mg for
1 month. OUTCOMES: After oral acetylspiramycin, topical and systemic
corticosteroids for 3 months, the retinal lesions were scarred, and inflammation
of the anterior chamber and vitreum disappeared. After a 9-month follow-up, the
visual acuity was 0.6, and no active lesions were observed in the fundus.
LESSONS: The immunocompetent elderly who are in contact with domestic cats may
have an opportunistic infection with toxoplasmosis leading to primary
retinochoroiditis. Prompt diagnosis and effective treatment can get a good
clinical prognosis.
PMID- 29952986
TI - Clinical aspects of bile culture in patients undergoing laparoscopic
cholecystectomy.
AB - Bile is aseptic; under conditions of no external influx, there is a less than 30%
chance of isolating bacteria even in acute cholecystitis. This study was
conducted to evaluate the incidence of biliary microflora and most common biliary
microflora and resistance to antibiotics in patients with cholecystitis, as well
as predict situations that do not require the use of prophylactic
antibiotics.Bile samples were collected for culture using standard methods during
all cholecystectomies performed from January 2015 to December 2015 in the
Department of Surgery, Pusan National University Hospital. A total of 366
laparoscopic cholecystectomies were performed during the study period. In 215
patients, bile culture was performed and cultures were positive in 54 cases.
Prophylactic antibiotics with 2nd-generation cephalosporin were administered once
30 minutes before surgery. According to the results of bile culture, patients
were divided into 2 groups, culture-negative and culture-positive groups.
Preoperative, intraoperative, and postoperative factors were compared between
groups.The culture positive group was older (P = .000). The number of patients
with performance of endoscopic retrograde cholangiopancreatography (ERCP),
performance of percutaneous transhepatic gallbladder drainage (PTGBD), presence
of symptoms, presence of operative complications, and hospital stay was
significantly higher in the culture-positive group than in culture-negative
group. In multivariate analysis of factors associated with positive culture, age,
ERCP, and symptoms were independent factors affecting positive bile culture.
Eighty-five bacteria were identified in 54 patients. Escherichia coli and
Klebsiella were common in gram-negative bacteria. Enterococcus was the most
common in gram-positive bacteria. Less than 5% resistance was observed against
carbapenem, beta-lactam antibiotics, glycopeptide antibiotics, and linezolid.The
bile of patients with laparoscopic cholecystectomy may contain microorganisms,
particularly elderly patients, those with symptoms, and those who undergo
preoperative ERCP. When ERCP was performed, multiple bacteria culture-positive
results were more likely to be found. Although carbapenem, beta-lactam
antibiotics, glycopeptide antibiotics, and linezolid may be suitable prophylactic
antibiotics, additional studies of the clinical aspects of culture-positive bile
is needed to determine the importance of bacterial growth in bile.
PMID- 29952988
TI - Uncommon foreign body in the hypopharynx: A case report.
AB - RATIONALE: Pharyngeal foreign bodies are a common complaint in emergent cases,
and sometimes can be lethal. A large variety of foreign bodies may lodge in the
pharynx. We present a case of uncommon foreign body in the hypopharynx. PATIENT
CONCERNS: A 9-month-old boy presented for an hour of crying associated with
having congee. No abnormality was revealed in physical examination or
cervicothoracic computed tomography (CT) scan. Flexible laryngoscopy showed a
size tag on the posterior hypopharyngeal wall. DIAGNOSES: Foreign body in the
hypopharynx. INTERVENTIONS: The foreign body was removed from the hypopharynx.
OUTCOMES: The patient was discharged after the removal of the foreign body.
LESSONS: Infants with foreign bodies in the hypopharynx may presented with no
obvious clinical manifestation. Pharyngeal foreign bodies may be the potential
for disastrous consequences. Otolaryngologists should pay attention to these
foreign bodies.
PMID- 29952987
TI - Abnormal default-mode network homogeneity in patients with temporal lobe
epilepsy.
AB - Default-mode network (DMN) plays a key role in a broad-scale cognitive problem,
which occurs in temporal lobe epilepsy (TLE). However, little is known about the
alterations of the network homogeneity (NH) of DMN in TLE. In the present study,
we employed NH method to investigate the NH of DMN in TLE at rest.A total of 47
patients with TLE (right TLE [rTLE] 29, and left TLE [lTLE] 18) and 35 healthy
controls who underwent resting-state functional magnetic resonance imaging were
enrolled. NH approach was used to analyze the data.rTLE exhibited decreased NH in
the right middle temporal pole gyrus and increased NH in the bilateral posterior
cingulate cortex compared to the control group. In lTLE, decreased NH was
observed in left inferior temporal gyrus and left hippocampus. Meanwhile, we
found that lTLE had a longer performance reaction time. No significant
correlation was found between abnormal NH values and clinical variables in the
patients.These findings suggested that abnormal NH of the DMN exists in rTLE and
lTLE, and highlighted the significance of DMN in the pathophysiology of cognitive
problems occurring in TLE and also found the existence of abnormality of
executive function in lTLE.
PMID- 29952989
TI - Extent and location of fixation affects the biomechanical stability of short- or
long-segment pedicle screw technique with screwing of fractured vertebra for the
treatment of thoracolumbar burst fractures: An observational study using finite
element analysis.
AB - Intermediate screw fixation at the fracture level has been widely accepted to
treat thoracolumbar burst fractures, but no study has shown the effect of the
extent and location of fixation. The effect of the extent and location of
fixation on short- or long-segment pedicle screw fixation through intermediate
screw fixation at the fracture level in the treatment of thoracolumbar burst
fractures is discussed.Posterior intermediate screw fixation techniques in
treating T12 vertebral fracture models were simulated and compared using finite
element methods; the fixation techniques included M3-L1 (bilateral 3 monoaxial
pedicle screw fixation from L1 to T11), M3-L2, M4-L1 (bilateral 4 monoaxial
pedicle screw fixation from L1 to T10), M4-L2, M4-L3, and M5-L2 (bilateral 5
monoaxial pedicle screw fixation from L2 to T10). Range of motion (ROM) and
largest von Mises stress (LVMS) of the instrumentations were recorded and
analyzed.No significant differences were observed in the mean ROM of all states
of motion between the M3-L1 model and the other fixation models except for M5-L2.
The LVMS of the pedicle screws and rods all occurred during flexion. The LVMS
values of the pedicle screws were larger in the M3-L2 fixation model and M4-L3
fixation model than in the other fixation models. The M3-L1 model presented a
significantly smaller mean LVMS of the pedicle screws in all states of motion
than the M3-L2 model (P = .026). The LVMS values of the rods were larger in the
M3-L2 fixation model, M4-L3 fixation model, and M4-L2 fixation model than in the
other fixation models. No significant differences were observed in the mean LVMS
of the rods in all states of motion among all the fixation models.When choosing
short-segment pedicle screw fixation with the screwing of fractured vertebrae to
treat thoracolumbar fractures, we suggest M3-L1 over M3-L2. More severe injuries
can be considered to identify an alternative treatment to long-segment monoaxial
pedicle fixation constructs such as the M4-L1 and M5-L2 techniques.
PMID- 29952990
TI - Descemet membrane endothelial keratoplasty using ophthalmic viscoelastic devices
for eyes with laser iridotomy-induced corneal endothelial decompensation:
Analysis of 11 eyes.
AB - Graft insertion into the anterior chamber is one of the most important procedures
for successful Descemet membrane endothelial keratoplasty (DMEK). Especially in
eyes with fragile zonular fibers and a shallow anterior chamber, smooth graft
insertion tends to become more difficult. Ophthalmic viscoelastic devices (OVDs)
can usually help to retain the space in the anterior chamber and to improve the
safety of manipulations during various ophthalmic surgeries. Therefore, we
postulated that graft insertion into the anterior chamber could be improved by
their use. The purpose of this study is to investigate the availability and
efficacy of OVDs during graft insertion in DMEK surgery.A total of 11 eyes of 9
patients with bullous keratopathy who underwent DMEK were retrospectively
analyzed. The cause of bullous keratopathy was corneal endothelial decompensation
following laser iridotomy in all eyes. We used low viscous dispersive OVD
(Opegan) to maintain the anterior chamber depth during graft insertion in all of
the eyes.The graft insertion was uneventful in all of the eyes. The inserted
graft was attached to the back surface of the cornea. However, 2 eyes needed
rebubbling, and after rebubbling, all of the 2 grafts completely attached to the
back surface of the cornea. The best spectacle-corrected visual acuity
significantly improved 6 months after surgery (P < .001) and the central corneal
thickness significantly decreased (P < .001).The use of OVD facilitates safer
graft insertion during DMEK, and subsequently prevents endothelial cell loss,
which leads to a successful procedure.
PMID- 29952991
TI - Predicting outcomes of acute low back pain patients in emergency department: A
prospective observational cohort study.
AB - Low back pain (LBP) is a common complaint among patients presenting to emergency
department (ED) in Singapore. The STarT Back Screening Tool (SBT) was recently
developed and validated for triage of LBP patients in primary care settings. This
study aimed to investigate whether the SBT could provide prognostic information
for long-term outcomes of acute LBP patients visiting the ED, who might benefit
from appropriate and timely management at an earlier stage.Data were collected in
a prospective observational cohort study from 177 patients who consulted
emergency physicians for acute LBP and completed 6-month follow-up. Patients were
administered the SBT and assessed at baseline. Follow-up assessments were
conducted at 6 weeks and 6 months.A multiple linear regression model
incorporating SBT total score, age, employment status, LBP history, and 6-week
pain score was constructed to predict 6-month pain score. In the model, SBT total
score and 6-week pain score were significantly associated with 6-month pain score
(P < .05) with respective coefficients of 0.125 and 0.500. The model explained
40.1% of the variance for 6-month pain score.This study demonstrated that the
multiple linear regression model showed predictive performance in determining
long-term outcomes for acute LBP patients presenting to the ED.
PMID- 29952993
TI - Effects of dry needling in an exercise program for older adults with knee
osteoarthritis: A pilot clinical trial.
AB - BACKGROUND: Few studies have investigated the dry needling (DN) approach on knee
osteoarthritis (KO) patients. The study's aim was to evaluate the short-term
efficacy of adding DN to a therapeutic exercise protocol in the treatment of KO
in older adults. METHODS: A double-blind, pilot clinical trial with parallel
groups [NCT02698072] was carried out for 12 weeks of treatment and follow-up.
Twenty patients aged 65 years and older with myofascial trigger points (MTrPs) in
the muscles of the thigh were recruited from older-adult care centers and
randomly assigned to a DN + Exercise group or a Sham-DN + Exercise group. The
Numeric Rating Scale (NRS; primary outcome) and Western Ontario and McMaster
Universities Osteoarthritis Index questionnaire (WOMAC) were assessed before and
after the intervention. RESULTS: The NRS (analysis of variance, ANOVA) showed
statistically significant differences in the time factor (F = 53.038; P < .0001;
etap = 0.747). However, it did not show a significant change in the group-time
interaction (F = 0.082; P = .777; etap = 0.005). The WOMAC scores (ANOVA) showed
statistically significant differences in the time factor for total score WOMAC
questionnaire (F = 84.826; P < .0001; etap = 0.825), WOMAC pain (F = 90.478; P <
.0001; etap = 0.834), WOMAC stiffness (F = 14.556; P < .001; etap = 0.447), and
WOMAC function (F = 70.872; P < .0001; etap = 0.797). However, it did not show a
statistically significant change in the group-time interaction. CONCLUSION:
Despite the pain intensity and disability clinically relevant improvement for
both DN and Sham-DN combined with exercise, 6 sessions of DN added to a
therapeutic exercise program for older adults with KO did not seem to improve
pain intensity and functionality.
PMID- 29952992
TI - Association between RAD51 135 G/C polymorphism and risk of 3 common gynecological
cancers: A meta-analysis.
AB - AIM: Available data concerning the association between RAD51 135G/C (rs1801320)
polymorphism and the risk of 3 common gynecological cancers still could not reach
a consensus. Thus, we conducted a meta-analysis to explore the relationship.
METHODS: Several electronic databases and bibliographies of relevant articles
were screened to identify the studies up to July 2017. Then a meta-analysis was
performed to evaluate the connection between 3 common gynecological tumors'
susceptibility and RAD51 135G/C polymorphism in different inheritance models.
Simultaneously, we did subgroup analysis and sensitivity analysis if necessary.
RESULTS: A total of 11 articles including 14 studies involving 4097 cases and
5890 controls were included in this meta-analysis. Overall, RAD51 135G/C
polymorphism increased the risk of 3 common gynecological tumors. The subgroup
analysis stratified by cancer types- endometrial carcinoma (EC) and ovarian
cancer (OC)-showed that RAD51 135G/C polymorphism increased the risk of EC:
allele model (C vs G: odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.63
7.10, P < .00001), dominant model (CC + GC vs GG: OR = 2.28, 95% CI = 1.44-3.60,
P = .004), recessive model (CC vs GC + GG: OR = 10.27, 95% CI = 14.71-22.38, P <
.00001), and homozygous model (CC vs GG: OR = 7.26, 95% CI = 3.59-14.68, P <
.00001), but there was no significant association between RAD51 135G/C
polymorphism and OC. In the subgroup analysis stratified by source of controls, a
significantly increased risk was observed in hospital-based studies.
Nevertheless, the data showed RAD51 135G/C polymorphism had no link in population
based studies. CONCLUSIONS: This meta-analysis suggested that RAD51 135G/C
polymorphism was a risk factor for the three common gynecological tumors,
especially for EC among hospital-based populations.
PMID- 29952994
TI - The diagnosis and management of rare cystic liver metastases from nasopharyngeal
carcinoma: A case report.
AB - RATIONAL: Nasopharyngeal carcinoma (NPC) with cystic liver metastases is so
rarely observed that there are only three cases reported in the published
literature. PATIENT CONCERNS: We present a case of NPC that received complete
response after chemotherapy and definitive radiotherapy, but a liver cystic
lesion was revealed on abdominal sonogram three months after the initial therapy.
The cystic liver lesion initially resembled a simple liver cyst with fast growth,
and then evolved into an abscess-like mass after a short term. Though abscess
drainage was performed, and the mass shrank significantly, but it returned to
previous size two months later. DIAGNOSES: Surgical resection was administrated
both for diagnosis and treatment, and eventually the lesion was histologically
demonstrated to be a liver metastasis. Eight months after the partial
hepatectomy, cystic liver metastases recurred on computed tomography (CT) scan.
INTERVENTIONS: Though palliative systematic chemotherapy including paclitaxel,
cisplatin, gemcitabine, navobine and anti-epidemal growth factor receptor (anti
EGFR) molecular-targeted therapy were performed, the cystic metastases still
gradually progressed. Then Transcatheter Hepatic Artery Chemoembolization (TACE)
was administrated for five times, and all the lesions were obviously decreased in
size. OUTCOMES: After TACE treatment, the liver metastases maintained stable for
six months, but lung metastases were noted. Finally, the patient died of liver
failure. LESSONS: The rare cystic appearance may be a special form which exists
for liver metastases of NPC, indicating poor prognosis. Oncologists need to
enhance the recognition and diagnosis level of this type of metastases. Intense
follow-up and early diagnosis are important. While emphasizing the importance of
local therapy and personal principles for liver metastases, TACE may be a
preferred method for unresectable cystic liver metastases from NPC.
PMID- 29952995
TI - Predicting effective remifentanil concentration in 95% of patients to prevent
emergence cough after laryngomicroscopic surgery.
AB - Smooth emergence or cough prevention is a clinically important concern in
patients undergoing laryngomicroscopic surgery (LMS). The purpose of this study
was to estimate the effective concentration of remifentanil in 95% of patients
(EC95) for the prevention of emergence cough after LMS under propofol anesthesia
using the biased coin design (BCD) up-down method.A total of 40 adult patients
scheduled to undergo elective LMS were enrolled. Anesthesia induction and
maintenance were performed with target-controlled infusion of propofol and
remifentanil. Effective effect-site concentration (Ce) of remifentanil in 95% of
patients for preventing emergence cough was estimated using a BCD method
(starting from 1 ng/mL with a step size of 0.4 ng/mL). Hemodynamic and recovery
profiles were observed after anesthesia.According to the study protocol, 20
patients were allocated to receive remifentanil Ce of 3.0 ng/mL, and 20 patients
were assigned to receive lower concentrations of remifentanil, from 1.0 to 2.6
ng/mL. Based on isotonic regression with a bootstrapping method, EC95 (95% CI) of
remifentanil Ce for the prevention of emergence cough from LMS was found to be
2.92 ng/mL (2.72-2.97 ng/mL). Compared with patients receiving lower
concentrations of remifentanil, the incidence of hypoventilation before
extubation and extubation time were significantly higher in those receiving
remifentanil Ce of 3.0 ng/mL. However, hypoventilation incidence after extubation
and staying time in the recovery room were comparable between the 2 groups.Using
a BCD method, the EC95 of remifentanil Ce for the prevention of emergence cough
was estimated to be 2.92 ng/mL (95% CI: 2.72-2.97 ng/mL) after LMS under propofol
anesthesia.
PMID- 29952996
TI - A retrospective study of smoking cessation intervention among university
students.
AB - This retrospective study investigated the effect of smoking cessation
intervention (SCI) among university students in China.Around 192 eligible smokers
among university students were included, and were assigned to an intervention
group (n = 100), and a control group (n = 92). All included subjects in both
groups were recommended to increase fruits and vegetables consumptions.
Additionally, participants in the intervention group also underwent SCI therapy
for a total of 4 weeks. The outcome measurements consisted of a number of
students quit smoking, daily cigarettes, quit attempts, mean days of smoking in
the past 30 days, and also stage of change.After 4-week treatment, SCI neither
can decrease the number of students quit smoking (P = .21), daily cigarettes (P =
.21), quit attempts (P = .07), and mean days of smoking in past 30 days (P =
.77), nor can enhance the stage of change (precontemplation, P = .18;
contemplation, P = .59; preparation, P = .46).The results of this study showed
that after 4-week therapy, SCI may be ineffective for smokers among university
students in Chinese.
PMID- 29952997
TI - The analgesic efficacy of transverse abdominis plane block versus epidural
analgesia: A systematic review with meta-analysis.
AB - BACKGROUND: The aim of the study was to compare the analgesic efficacy of
epidural analgesia and transverse abdominis plane (TAP) block. TAP block has
gained popularity to provide postoperative analgesia after abdominal surgery but
its advantage over epidural analgesia is disputed. METHODS: We followed the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
statement guidelines. Only trials comparing TAP block with epidural analgesia
were included. The primary outcome was pain score at rest (analog scale, 0-10) on
postoperative day 1 analyzed in subgroups according to the population (children
and adults). Secondary outcomes included rate of hypotension, length of stay, and
functional outcomes (time to first bowel sound, time to first flatus). RESULTS:
Ten controlled trials, including 505 patients (195 children and 310 adults), were
identified. Pain scores at rest on postoperative day 1 were equivalent for TAP
block and epidural analgesia groups in children (mean difference: 0.3; 95%
confidence interval [CI]: -0.1 to 0.6; I = 0%; P = .15) and in adults (mean
difference: 0.5; 95% CI: -0.1 to 1.0; I = 81%; P = .10). The quality of evidence
for our primary outcome was moderate according to the GRADE system. The epidural
analgesia group experienced a higher rate of hypotension (relative risk: 0.13;
95% CI: 0.04-0.38; I = 0%; P = .0002), while hospital length of stay was shorter
in the TAP block group (mean difference: -0.6 days; 95% CI: -0.9 to -0.3 days; I
= 0%; P < .0001), without impact on functional outcomes. CONCLUSION: There is
moderate evidence that TAP block and epidural analgesia are equally effective in
treating postoperative pain in both pediatric and adult patients, while TAP block
is associated with fewer episodes of hypotension and reduced length of stay.
PMID- 29952998
TI - Mobile phone application for self-assessment of acute stroke patients: A tool for
extended care and follow-up.
AB - We aimed to assess the accuracy of self-assessment for acute stroke patients via
mobile phone application-based scales and determine the value and prospect of
clinical use.A cross-sectional study was designed and acute stroke patients were
enrolled. We pushed the modified Rankin scale (mRS) and activities of daily
living (ADL) scale to patients via mobile phone application for self-assessment
on the day before they were out of hospital. We compared the results from nurse
assessment and self-assessment.Around 50 patients with the average age 51.72 +/-
12.40 completed the self-assessment. A total of 27 patients self-assessed the
scales, while caregivers of other 23 patients completed the assessment. In
comparison with patient assessment and nurse assessment, significant difference
was found in ADL score (P = .004), but was not found in mRS score (P > .05). When
comparing caregiver assessment with nurse assessment, no significant difference
could be found either in ADL score (P > .05) or in mRS score (P > .05). The kappa
value for self-assessment and nurse agreement of ADL was 0.720 (P = .000), with
sensitivity 96.8% and specificity 82.0%. The kappa value for self-assessment and
nurse agreement of mRS was 0.718 (P = .000), with sensitivity 97.6% and
specificity 92.4%.In summary, mobile phone application-based scales are generally
accurate, economical and convenient for self-assessment of acute stroke patients
with acceptable reliability in our small scale study. Caregivers can serve as the
proper assessor when patients are out of hospital. Therefore, it is promising but
still need to be further confirmed how practical to use this application in
extended care and follow-up.
PMID- 29952999
TI - A retrospective study of neuromuscular electrical stimulation for treating women
with post-stroke incontinence.
AB - This retrospective study evaluated the effect of using neuromuscular electrical
stimulation (NMES) for the treatment of post-stroke urinary incontinence (PSUI)
among female population in China.A total of 163 eligible patients with PSUI were
included in this study. Of these, 103 patients were assigned to a treatment
group, and 60 subjects were assigned to a control group. All patients in both
groups received bladder training. In addition, patients in the treatment group
also received NMES. All patients were treated for a total of 8 weeks. The outcome
measurements included the amount of urine leakage, urinary symptoms and quality
of life. The urinary symptoms were measured by the Bristol Female Urinary
Symptoms Questionnaire (BFUSQ) score, and the quality of life was assessed by the
International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)
score. In addition, adverse events were also documented in this study.After 4
week treatment, patients who received NMES did not exert better outcomes in the
amount of urine leakage, urinary symptoms, measured by BFUSQ scale, and the
quality of life, assessed by ICIQ-SF scale. However, after 8-week treatment,
patients in the treatment group showed greater effect in reducing the amount of
urine leakage (P < .01), enhancing urinary symptoms, as measured by BFUSQ scale
(P < .01), and improving the quality of life, as assessed by ICIQ-SF scale (P <
.01), compared with patients in the control group. In addition, no adverse event
was recorded during the period of 8-week treatment in this study.The results of
this study indicated that NMES may benefit for patients with PSUI after 8-week
treatment. Future studies should focus on warranting the results of this study.
PMID- 29953000
TI - Effect of neuromuscular electrical stimulation for endometriosis-associated pain:
A retrospective study.
AB - This retrospective study evaluated the effect of neuromuscular electrical
stimulation (NMES) for the treatment of endometriosis-associated pain (EAP).A
total of 154 patients with EAP were included and were divided into 2 groups in
this retrospective study. Eighty-three patients were assigned a treatment group,
and underwent NMES therapy, while 71 subjects in the control group were at
waiting list. The primary outcome of pain was measured by the numerical rating
scale (NRS) and the Endometriosis Symptom Severity scale (ESSS). The secondary
outcome was quality of life, measured by the 36-Item Short Form Health Survey (SF
36). All outcomes were measured before and after 5-week and 10-week treatment.
Moreover, we also recorded the adverse events in this study.After 5-week
treatment, no significant differences in all outcome measurements were found
between the 2 groups. However, after 10-week treatment, NMES therapy exerted
better outcomes in NRS (P = .02), ESSS (P = .04), and SF-36 [Physical Component
Summary (PCS), P < .01; Mental Component Summary (MCS), P < .01], compared with
the patients at the waiting list. Moreover, no significant differences of all
adverse events were found between the 2 groups, although mild and acceptable
adverse events occurred in the treatment group.This study demonstrated that NMES
is effective for treating patients with EAP.
PMID- 29953001
TI - Effect of voice rehabilitation training on the patients with laryngeal cancer
after radiotherapy.
AB - This retrospective study examined the effect of voice rehabilitation training
(VRT) for patients with laryngeal cancer (LC) after radiotherapy.Eighty-three
eligible patients with LC were included. Forty-three patients were assigned to a
treatment group, and underwent VRT, while the other 40 subjects were assigned to
a control group, and were at waiting list. Primary outcome was measured by the
Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale. Secondary
outcome was measured by Patient Perception Measures. All outcomes were measured
before and 3 months after VRT intervention.Patients in the treatment group did
not show better outcomes, measured by GRBAS scale (Grade, P = .78; Roughness, P =
.61; Breathiness, P = .83; Ashenia, P = .89; and Strain, P = .41), and Patient
Perception Measures (Vocal quality, P = .17; Acceptability, P = .35; Hoarseness,
P = .23; Vocal fatigue, P = .39; and Ashamed, P = .51), compared with patients in
the control group.The results of this study did not exert better outcomes in
patients received VRT than those at waiting list.
PMID- 29953002
TI - Primary central nervous system histiocytic sarcoma: A case report and review of
literature.
AB - RATIONALE: Primary central nervous system histiocytic sarcoma (PCNSHS) is a rare
lymphohematopoietic tumor with a histiocytic cell origin. To our knowledge, only
28 cases have been published in English and 2 cases in Chinese. PATIENT CONCERNS:
A 49-year-old Asian female presented to the hospital with a 2 month history of
hypomnesia, odynophagia, and gait disorder. Physical examination demonstrated
decreased lower extremity muscle strength. The patient denied a history of
malignancy. DIAGNOSES: Radiology demonstrated a lesion in parietal lobe with
uniformenhancement. Histologic analysis showed pleomorphic tumor cells with a
loose arrangement, effacing the normal brain tissue. The tumor cells exhibited
abundant eosinophilic cytoplasm, highly atypical nuclei and predominant nucleoli.
Immunohistochemistry revealed positive immunoreactivity for CD45, lysozyme, CD68,
and CD163, and negative for pan-cytokeratin (CK), epithelial membrane antigen
(EMA), glial fibrillary acidic protein (GFAP), CD3, CD20, CD1a, CD79a, CD138,
oligodendrocyte transcription factor (olig2), CD15, melan-A, CD30, CD21, CD35,
Human Melanoma Black-45 (HMB45), and anaplastic lymphoma kinase-1 (ALK-1). The
diagnosis of PCNSHS was rendered. INTERVENTIONS: The patient underwent complete
surgical resection and adjuvant radiotherapy. OUTCOMES: Follow-up information
shows the patient died 8 months following the initial diagnosis. LESSONS: PCNSHS
is extremely rare with an aggressive clinical course. Immunohistiochemistry is
necessary to make this diagnosis and to exclude other primary intracranial and
lymphohematopoietic tumors. Further research is required to improve the outcome
of patients with PCNSHS.
PMID- 29953003
TI - Accuracy of a nomogram to predict the survival benefit of surgical axillary
staging in T1 breast cancer patients.
AB - T1 breast cancer patients have favorable clinical outcomes, so that whether
axillary stating (AS) surgery can be omitted in these patients is still unclear.
This retrospective cohort study developed a nomogram to predict the cancer
specific survival (CSS) of T1 breast cancer patients with and without AS and
estimate the survival benefit of AS in these patients.We used surveillance,
epidemiology, and end results (SEER) database to identify 232,195 breast cancer
patients with T1 tumors diagnosed between 1990 and 2008. In the training cohort,
we used the Kaplan-Meier method and the competing risk analysis, with non-CSS as
the competing risk, to screen for prognostic factors for CSS. A nomogram to
predict the CSS, with receiving AS or not as one of the predictors, was developed
and externally validated, using the C-index and calibration plots. The survival
benefit of AS can be estimated by the difference of 2 predicted CSS, when the
patient was considered as having and not having AS.With a median follow-up of 109
months, the CSS of the study population were 96.3%, 92.3%, and 88.5% at 5, 10,
and 15 years, respectively. Significant predictors for CSS identified in the
training cohort were used to develop a nomogram, which was validated internally
[C-index = 0.707, 95% confidence interval (95% CI) 0.702-0.712] and externally (C
index = 0.704, 95% CI 0.698-0.710). The nomogram was well calibrated. With this
nomogram, AS was predicted to have less than 2% benefit of 5-, 10-, and 15-year
CSS in 60.6% (140,599/232,195), 15.5% (36,074/232,195), and 8.6% (20,043/232,195)
of the entire study population, respectively.The new nomogram can accurately
predict the CSS of T1 breast cancer patients, and also be able to estimate the
survival benefit of AS in these patients. Prospective studies are needed to
confirm our findings.
PMID- 29953004
TI - Foreign body embedded in the lower esophageal wall located by endoscopic
ultrasonography: A case report.
AB - RATIONALE: Ingested esophageal foreign bodies are commonly seen in adult
population. In very few instances, esophageal foreign body may pass through the
mucosal surface, re-epithelialize or migrate into surrounding soft tissues.
PATIENT CONCERNS: A 55-year-old Chinese male was admitted to our hospital with a
10-day history chest and upper abdominal pain without dysphasia, cough or other
symptoms. DIAGNOSES: We initially suspected chronic gastritis, and thoracic
computed tomography and endoscopy ultrasonography (EUS) were used to identify a
fish bone completely embedded within the lower esophageal wall. INTERVENTIONS:
Under the EUS-guidance, we marked the foreign body using methylene blue with
saline solution, which was followed by successful thoracoscopy and surgical
removed of the foreign body. OUTCOMES: The patient recovered well and was
discharged 1 week postoperatively. One month postoperatively, the patient was
symptom free and the chest wound was complete healed. LESSONS: Our case showed
that computed tomography is necessary to diagnose the esophageal foreign body,
and EUS may help confirm the position of foreign body, especially those embedded
in the esophageal submucosa. We advocate necessary surgery at the first accurate
diagnosis in patient with esophageal foreign body when endoscopy is not possible.
PMID- 29953005
TI - Association of XPA polymorphism with breast cancer risk: A meta-analysis.
AB - BACKGROUND: The association of XPA rs1800975 polymorphism with breast cancers has
been reported in several studies, but the results were conflicting. In order to
analyze the association between XPA rs1800975 polymorphism and the risk of breast
cancer, a meta-analysis was performed in the present study. METHODS: The
literature search for relevant studies was conducted in PubMed, Embase, Cochrane
Library, China National Knowledge Infrastructure (CNKI), and Wanfang Med Online
databases. The odds ratios (ORs) and their corresponding 95% confidence intervals
(95% CIs) were calculated using fixed-effect/random-effects models by the STATA
12.0 software. The sources of heterogeneity were analyzed by subgroup analysis.
RESULTS: Six case-control studies involving 5069 subjects (2338 patients and 2731
healthy controls) were included in the present meta-analysis. In the pooled
analysis, no obvious association was found between XPA rs1800975 polymorphism and
the risk of breast cancer in all genetic models. However, in subgroup analysis
based on ethnicity, XPA rs1800975 polymorphism was found to be related to
decreased breast cancer risk in non-Asians in the recessive model (OR = 0.80, 95%
CI = 0.64-1.00, P = .045). Moreover, source of control subgroup analysis
demonstrated that XPA rs1800975 polymorphism might decrease the risk of breast
cancer in population-based group in the recessive model (OR = 0.80, 95% CI = 0.64
1.00, P = .045). CONCLUSION: XPA rs1800975 polymorphism may decrease the risk of
breast cancer in both non-Asians and population-based patients. Large sample size
and well-designed study is needed for further assessing the role of XPA
polymorphism in breast cancer risk.
PMID- 29953006
TI - Sudden death in a patient with severe mitral annular calcification and end-stage
renal disease during hemodialysis: A case report.
AB - RATIONALE: Mitral annular calcification (MAC) is a chronic, degenerative cardiac
condition. Although MAC is often considered as an incidental finding in clinical
and forensic practice, sudden death due to severe MAC with end-stage renal
disease (ESRD) during hemodialysis is uncommon. In addition, spontaneous
subepicardial hematoma due to rupture of the subepicardial vein is very rare.
PATIENT CONCERNS: A 65-year-old woman had a history of hypertension, diabetes
mellitus, and renal failure. DIAGNOSES: Postmortem examination revealed marked
MAC with cardiomegaly and ESRD. Spontaneous subepicardial hematoma due to
disruption of subepicardial vein was also seen. INTERVENTIONS AND OUTCOMES: The
patient became short of breath while on hemodialysis and expired en route to the
hospital. LESSONS: In this case, death was attributed to the effects of the
calcified mitral valve annulus. This case highlights that MAC must be considered
in any patient with ESRD and fatal cardiovascular events should not be overlooked
in these patients.
PMID- 29953007
TI - Magnetic resonance imaging in the prediction of aggressive histological features
in papillary thyroid carcinoma.
AB - To identify magnetic resonance imaging (MRI) features in the prediction of tumor
aggressiveness in patients with papillary thyroid carcinoma (PTC).In this
prospective study, 105 patients with 122 PTCs underwent MRI with T1-weighted, T2
weighted, diffusion-weighted imaging and contrast-enhanced sequences prior to
thyroidectomy. Based on exclusion criteria, 62 patients with 62 PTCs were finally
suitable for further analysis. Tumor aggressiveness was defined according to the
surgical histopathology. Tumor size, apparent diffusion coefficients (ADC) value
and MRI features on images were obtained for each patient. Descriptive statistics
for tumor aggressiveness, sensitivity, specificity, and accuracy of individual
features were determined. A multivariate logistic regression model was developed
to identify features that were independently predictive for tumor aggressiveness.
Analyses of receiver-operating characteristic (ROC) curve were performed.High
aggressive PTC significantly differed from low aggressive PTC in size (P = .016),
size classification (P < .001), ADC value (P = .01), angulation on the lateral
surface of the lesion (P = .009), signal intensity heterogeneity on ADC maps (P =
.003), early enhancement degree (P < .001), tumor margin on delayed contrast
enhanced images (P < .001), and inner lining of delayed ring enhancement (P =
.028). The interobserver agreement between the 2 readers was satisfactory with
Cohen k ranging from 0.83 to 1.00 (P < .001). Logistic regression model showed
lesion size classification and tumor margin on delayed contrast-enhanced images
as strongest independent predictors of high aggressive PTC (P = .009 and P =
.047), with an accuracy of 83.9%. The area under ROC curve for ADC value and
lesion size were 0.68 and 0.81, respectively.These findings suggest that MRI
before surgery has the potential to discriminate tumor aggressiveness in patients
with PTC.
PMID- 29953008
TI - Concomitant tonsillar cyst and papilloma in larynx: A case report.
AB - RATIONALE: Laryngeal cysts are rare lesions that may occur at any mucosa-lined
location within the larynx. Papillomas are also benign lesions of the larynx.
PATIENT CONCERNS: We report a 34 year-old-patient with a laryngeal cyst
incidentally found during screening endoscopy and presenting as a soft tissue
mass on a computerized tomography scan. A papilloma concomitant with the cyst was
detected intraoperatively. DIAGNOSES: Concomitant tonsillar cyst and papilloma of
the larynx. INTERVENTIONS: The lesion was completely resected with a bipolar
radiofrequency plasma ablation (RFA) device. OUTCOMES: Pathologic examination
showed a tonsillar cyst and papilloma in the larynx. Six months later, there has
been no evidence of recurrence. LESSONS: To our knowledge, this is the first
report of a concomitant tonsillar cyst and a papilloma in the larynx.
Asymptomatic laryngeal cysts can be detected endoscopically. RFA is safe and
effective for endoscopic management.
PMID- 29953009
TI - Rhabdomyolysis following status epilepticus with hyperuricemia: A case report and
literature review.
AB - RATIONALE: Rhabdomyolysis owing to status epilepticus (SE) can be life-threating,
with acute kidney injury (AKI) the most serious complication; therefore, early
recognition of the risk factors is important. Hyperuricemia after epileptic
seizures has been reported, and severe hyperuricemia can lead to acute renal
function damage. PATIENT CONCERNS: We present the case of a 21-year-old man
hospitalized for SE, who had especially high level of blood uric acid (UA) at
initial presentation. DIAGNOSIS: The patient was diagnosed with rhabdomyolysis
due to SE. INTERVENTIONS: The patient was treated with hydration and bicarbonate
therapy. But he developed acute kidney failure (AKF) and hemodialysis was
performed. OUTCOMES: After hemodialysis, his symptoms disappeared and laboratory
data returned to normal. LESSONS: Hyperuricemia after SE might indicate severe
muscle damage or reduced clearance of metabolites, and could be a risk factor for
kidney dysfunction, especially with rhabdomyolysis. To our knowledge, this is the
first report of rhabdomyolysis following SE with hyperuricemia.
PMID- 29953010
TI - Rapid detection of urinary soluble intercellular adhesion molecule-1 for
determination of lupus nephritis activity.
AB - The current methods of monitoring the activity of lupus nephritis (LN) may cause
unnecessary hospital visits or delayed immunosuppressive therapy. We aimed to
find a urinary biomarker that could be developed as a home-based test for
monitoring the activity of LN.Urine samples were collected immediately before a
renal biopsy from patients of suspected active LN, and also from patients with
inactive LN, systemic lupus erythematous without LN or healthy controls.
Biomarker search was conducted on a cytokine antibody array and confirmation was
done by quantitative evaluation with enzyme-linked immunosorbent assay. The Mann
Whiney test or Student t test was used to compare the levels of 9 cytokines
between different groups. The sensitivity and specificity of each cytokine for
diagnosis of LN was evaluated by receiver operating characteristic curve. A rapid
test based on colloidal gold immunochromatography was then developed for bedside
or home use. Furthermore, an experimental e-healthcare system was constructed for
recording and sharing the results of the rapid test a cloud-assisted internet of
things (IoT) consisting of a sensing device, an IoT device and a cloud
server.Adiponectin (Acrp30), soluble intercellular cell adhesion molecule-1
(sICAM-1), neural cell adhesion molecule 1 (NCAM-1), and CD26 were significantly
higher in urine samples of active LN patients. sICAM-1 appeared more sensitive
and specific among these candidates. When the cut-off value of sICAM-1 was set at
1.44 ng/mL, the sensitivity reached 98.33% with a specificity at 85.71%. The
sICAM-1 strip test showed comparable sensitivity of 95% and a specificity of
83.3% for assessing the LN activity. Meanwhile, the e-healthcare system was able
to conveniently digitize and share the sICAM-1 rapid test results.sICAM-1
appeared to be an excellent biomarker for monitoring LN activity. The e
healthcare system with cloud-assisted IoT could assist the digitalization and
sharing of the bedside or home-based sICAM-1 test results.
PMID- 29953011
TI - Prevalence and factors associated with nonalcoholic fatty pancreas disease and
its severity in China.
AB - Pancreatic lipidosis (nonalcoholic fatty pancreas disease, NAFPD) causes insulin
resistance and dysfunction of pancreatic beta-cells, with the risk of type 2
diabetes mellitus (T2DM). However, the prevalence and pathogenic factors
associated with NAFPD are not clear. The aim of the study was to explore the
prevalence of NAFPD in a Chinese adult population, and investigate factors
associated with NAFPD aggravation.This was a cross-sectional study; 4419 subjects
were enrolled for NAFPD screening and were divided into NAFPD (n = 488) and
without NAFPD (n = 3930) groups. The sex, age, related concomitant diseases,
general physical parameters, and serum glucose and lipid metabolism were compared
between the 2 groups.The overall NAFPD prevalence was 11.05%, but increased with
age. In those <55 years NAFPD prevalence was lower in females than males (P <
.05), but prevalence was similar >55 years. Nonalcoholic fatty liver disease
(NAFLD), T2DM, homeostasis model assessment-insulin resistance index, total
cholesterol, triglyceride, lipoprotein, adiponectin, and glucagon-like peptide 1
(GLP-1) were the independent risk factors for NAFPD (P < .05). Analaysis of mild
NAFPD (MN) and severe NAFPD (SN) subgroups, according to the extent of fat
deposition, suggested that NAFLD, triglyceride, lipoprotein, and adiponectin were
independent risk factors for NAFPD aggravation (P < .05).The NAFPD prevalence was
about 11% in Chinese adults. Its development and progression was related to
NAFLD, T2DM, insulin resistance, dyslipidemia, and GLP-1 levels. Severe NAFPD was
associated with NAFLD and dyslipidemia.
PMID- 29953012
TI - Unusual location of the glomus tumour in the liver: A case report and literature
review.
AB - RATIONALE: Liver glomus tumor is very rare, and only 6 cases have been reported.
Herein, we report another case of liver glomus tumor and the clinicopathological
features are summarized. PATIENT CONCERNS: An 18-year-old male patient was
admitted due to hypertension and arrhythmia for 4 days. DIAGNOSES: Abdominal
enhanced CT revealed a 6.0-cm solid and cystic mass in the left liver lobe. The
mass was collected by hepatic lobectomy. Microscopically, the tumor cells were
round or oval, and had no malignant features and no evident atypia.
Immumohistochemically, tumor cells were positive for positive for SMA and
vimentin, but partially positive for syn, CD34 and desmin. He was pathologically
diagnosed with liver glomus tumor. INTERVENTIONS: The patient underwent a left
hepatic lobectomy. OUTCOMES: After surgery, this patient was followed up for 6
months, and metastasis/recurrence was not observed. LESSONS: Primary liver glomus
tumor has no specific clinical manifestations, and imaging examinations have
limitations for its diagnosis. Immunostaining for SMA and vimentin is necessary
to prove the diagnosis. Complete resection is strongly advised and it has a
favorable prognosis.
PMID- 29953013
TI - Efficacy of Yokukansankachimpihange on sleep disturbance in Parkinson's disease:
A study protocol of a randomized, double blind, placebo-controlled pilot trial.
AB - INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative
disorder that includes motor and nonmotor symptoms. Sleep disturbance is known to
decrease the quality of life in patients with PD, and there are limitations to
the pharmacotherapy currently in use. Therefore, complementary treatment
therapies are required to address these limitations. The traditional herbal
medicines Yokukansan (YKS) and Yokukansankachimpihange (YKSCH) have been used to
treat insomnia and night crying in children, suggesting their effectiveness
against sleep disturbance in patients with PD. We will evaluate whether YKSCH
improves sleep disturbance in PD and will identify YKS-related changes in
hemodynamic parameters, and neurotransmitter and hormone levels in patients with
PD experiencing sleep disturbance. METHODS: We will conduct a randomized, double
blinded, placebo-controlled parallel trial in 34 patients with PD and sleep
disturbance, randomly allocating the patients to either placebo-control (n = 17)
or treatment groups (n = 17). The total study period will be 16 weeks;
administration of YKSCH or placebo, as intervention, will be performed for a 12
week period, and follow-up will be performed over a 4-week period. All subjects
will undergo conventional treatment, and be required to maintain a regular
medication schedule throughout the study period. The primary outcome measure will
be the Scales for Outcomes in PD-Sleep Scale score, and the secondary outcome
measures will be polysomnography results, findings from instruments related to
sleep disorders, neurotransmitter and hormone levels, and hemodynamic changes in
the brain cortex. DISCUSSION AND CONCLUSIONS: This trial will evaluate the
effectiveness and safety of YKSCH for sleep improvement in PD with sleep
disturbance, and investigate the underlying mechanism of action. We expect
improvement in the scores for subjective and objective sleep scales, hemodynamic
changes in prefrontal cortical activity, and changes in neurotransmitter and
hormone levels. The findings will provide insight into the mechanism underlying
the therapeutic effect of YKSCH in PD, and lay the foundation for further studies
on whether YKSCH improves sleep disturbance in PD. TRIAL REGISTRATION NUMBER:
Clinical Research Information Service (KCT0002869).
PMID- 29953014
TI - Study protocol and rationale for a prospective, randomized, double-blind, placebo
controlled study to evaluate the effects of Ashwagandha (Withania somnifera)
extract on nonrestorative sleep.
AB - : Nonrestorative sleep (NRS) is one of the cardinal symptoms of insomnia and can
occur independent of other components of insomnia. Among the sleep disturbances,
NRS has been little studied in the general population, even though this symptom
plays an important role in several medical conditions associated with chronic
inflammation such as heart disease, fibromyalgia, and chronic fatigue syndrome,
as well as various sleep disorders. There is paucity in the literature about
effective treatments for NRS. Ashwagandha (Withania somnifera) has been
demonstrated to reduce anxiety and stress, allowing the body to settle down and
prepare for sleep. This study will be a double-blind, randomized, placebo
controlled interventional study in NRS population.The NRS participants are
identified using Restorative Sleep Questionnaire-weekly version (RSQ-W)
questionnaire. Actigraphy and polysomnography are used for the objective
assessment of sleep. The other assessments used are Hamilton Anxiety Depression
Scale (HADS), World Health Organization Quality of Life (WHOQOL) scales, and C
reactive protein. Routine blood and urine analyses will be conducted to assess
the safety of treatment. Duration of study for each participant will be 50 days
with "day one" for screening followed by randomization for the treatment. The
duration for medicine/placebo intake shall be 42 days.Primary outcome will be to
evaluate effect of daily supplement of ashwagandha extract compared with placebo
in subjects with NRS at 6 weeks from baseline, as assessed by the total score of
RSQ-W. CTRI REGISTRATION NUMBER: CTRI/2017/02/007801.
PMID- 29953015
TI - Extrapyramidal signs occurring after sympathetic block for complex regional pain
syndrome responding to diphenhydramine: Two case reports.
AB - RATIONALE: To present an unusual extrapyramidal motor response occurring after a
sympathetic block in CRPS and its successful treatment with diphenhydramine.
PATIENT CONCERNS: Severe pain related to Complex Regional Pain Syndrome type 1
interfering with activities of daily living. DIAGNOSES: Complex Regional Pain
Syndrome type 1. INTERVENTIONS: We report a video case reports of two patients
with a diagnosis of CRPS type-I. Both patients exhibited similar presentation of
unusual extrapyramidal motor response of the affected limb following lumbar
sympathetic block. Both patients were treated with intravenous diphenhydramine to
abort the extrapyramidal motor response. OUTCOMES: Both patients similarly
responded to treatment with intravenous diphenhydramine with abrupt resolution of
the motor response. LESSONS: Sympathetic blockade may interfere with the adaptive
autonomic reflex circuits of the motor balance homeostasis in patients with
complex regional pain syndrome. Disinhibition of extrapyramidal system may lead
to immediate expression of extrapyramidal signs following the sympathetic block.
Diphenhydramine, with its anti-histaminic and anticholinergic properties, may be
effective in aborting such extrapyramidal signs, and should be considered as a
treatment option in similar cases.
PMID- 29953016
TI - IgG4-related retroperitoneal fibrosis overlapping with primary biliary cirrhosis
and primary Sjogren's syndrome: A case report.
AB - RATIONALE: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory
disorder which is characterized by elevated levels of serum IgG4 and infiltration
of IgG4-bearing plasma cells in the involved organs. Primary biliary cirrhosis
(PBC) and Primary Sjogren's syndrome (pSS) are both distinct from IgG4-related
disease. We herein describe a Chinese patient with IgG4-related RPF overlapping
with PBC and pSS. PATIENT CONCERNS: We report a case of 69-year-old male with
recurrent lower abdominal pain for 10 months. Laboratory data showed elevated
erythrocyte sedimentation rate and hepatobiliary enzymes, renal dysfunction, high
titers of antinuclear antibody, anti-SS-A antibody and anti-mitochondrial type 2,
high immunoglobulin (Ig) G levels and elevated serum IgG4 (9 g/L). Contrast
enhanced computed tomography and magnetic resonance imaging were suggestive of
retroperitoneal fibrosis and unilateral ureteral occlusion. Immunohistochemical
staining for IgG4 did not demonstrate infiltration of IgG4-positive plasma cells
in the retroperitoneal mass, but revealed significant infiltration of
lymphocytoplasma cells as well as fibrosis and fibrin accumulation. DIAGNOSES:
The patient was diagnosed with IgG4-related retroperitoneal fibrosis based on the
International Consensus Diagnostic Criteria. He was also diagnosed with primary
biliary cirrhosis and primary Sjogren's syndrome. INTERVENTIONS: 250 mg
ursodeoxycholic acid was administered twice daily, and prednisolone was initiated
at a dose of 40 mg/day and then tapered to 25 mg after 45 days. OUTCOMES: The
size of the retroperitoneal soft tissue mass gradually reduced and the abnormal
laboratory parameters were restored to normal. LESSONS: This rare clinical
condition has seldom been reported in the literature, which suggests that common
immunogenetic factors may be involved in the development of IgG-related RPF, PBC
and pSS.
PMID- 29953017
TI - Associations of dietary macronutrients and micronutrients with the traditional
and nontraditional risk factors for cardiovascular disease among hemodialysis
patients: A clinical cross-sectional study.
AB - The current study was to examine the association of adequate intake of
macronutrients and micronutrients with traditional and nontraditional
cardiovascular risk factors in hemodialysis patients.A clinical cross-sectional
study was conducted between September 2013 and April 2017 on 492 hemodialysis
patients aged 20 years and above, received thrice-weekly hemodialysis treatment
for at least 3 months, adequate dialysis quality (equilibrated Kt/V >= 1.2
g/kg/d) from 7 hospital-based hemodialysis centers in Taiwan. The dietary intake
was evaluated by the 3-day dietary record, and a 24-hour dietary recall.
Biochemical parameters were archived from laboratory tests. The cardiovascular
disease (CVD) risk factors were defined by the Kidney Disease Outcomes Quality
Initiative (K/DOQI) Clinical Practice Guidelines. The adequate dietary intake of
macronutrients and micronutrients was recommended by the European Best Practice
Guidelines, K/DOQI, and Institute of Medicine guidelines. Logistic regression
analysis was used.All hemodialysis patients had CVD risks, the lowest proportion
of patients with adequate intake of macronutrients and micronutrients were 8.7%
and 1.8%, respectively. The adequate dietary intake associated with lower
likelihood of having CVD risks in hemodialysis patient by 47% to 84%, including
39% to 58% lower hypertension, 37% to 50% lower dyslipidemia, 42% to 63% diabetes
mellitus, 44% to 84% lower obesity, 58% lower low calcium, 38% lower
hyperparathyroidism, 47% to 64% lower hyperhomocysteinemia, and 41% to 67% lower
inflammation, 63% to 74% lower hypoalbumin, 73% lower inadequate normalized
protein nitrogen appearance.Adequate dietary nutrients intake may reduce the
cardiovascular risks factors, in turn, to prevent the cardiovascular morbidity
and mortality.
PMID- 29953018
TI - Partial molar pregnancy in the cesarean scar: A case report and literature
review.
AB - RATIONALE: The incidence of molar pregnancy in the cesarean scar is exceedingly
low, however, the disease may carry a high risk of uncontrolled hemorrhage or
uterine rupture. So far managements of this disease were rarely reported in
literature. PATIENT CONCERNS: We reported a 28-year-old woman presented to our
hospital with a complaint of amenorrhea for 48 days and vaginal bleeding for 3
days. DIAGNOSIS: Transvaginal ultrasonography, serum hCG and pelvic MRI confirmed
the cesarean scar pregnancy. INTERVENTIONS: The patient underwent bilateral
uterine arterial embolization and suction evacuation. OUTCOMES: The postoperative
histologic examination of the tissue revealed a partial hydatidiform mole.
LESSONS: Molar pregnancy in the cesarean scar is tough to differentiate from
normal cesarean scar pregnancy with serum hCG, sonogram or MRI. This case
suggested us that it was necessary to perform a histological examination of
postoperative specimen for cesarean scar pregnancy.
PMID- 29953019
TI - Effects of physician's specialty on regular chronic kidney disease care in
predialysis: A population-based cross-sectional study.
AB - Late referral in chronic kidney disease (CKD) is associated with irregular care
and poor prognosis. How the specialty of healthcare provider affect late referral
and irregular CKD care remain unclear.We conducted a population-based cross
sectional study to include incident dialysis patients from 2002 to 2007 in Taiwan
and observed for 1, 2, and 3 years before dialysis. The medical visits-related
information was evaluated every 3 months, retrospectively. Irregular follow-up
was defined as missing a follow-up during more than one interval every year.A
total of 46,626 patients were included. At 1, 2, and 3 years prior to maintenance
dialysis, 87%, 66%, and 50% of patients had regular medical visits; however, only
49%, 23%, and 12% had estimated glomerular filtration rate (eGFR) regularly
monitored, respectively. Independent factors of less regular eGFR follow-up
included age (adjusted odds ratio (OR) 0.995, 95% confidence interval 0.993
0.998), cardiac disorder (0.90, 0.82-0.99), and stroke (0.76, 0.69-0.84), as well
as regular visits at some other specialties (adjusted OR range: from 0.77 to
0.88); whereas, independent factors of less regular visits at nephrology included
diabetes mellitus (0.48, 0.46-0.51), cardiac disorder (0.61, 0.56-0.66), stroke
(0.53, 0.48-0.58), and regular visits at any other specialty (adjusted OR range:
from 0.22 to 0.78).Regular medical visits were quite common in late CKD patients,
but they received regular eGFR measurement and visit at nephrology much less
frequently. Physicians play a major role in the late referrals in CKD and its
irregular care.
PMID- 29953020
TI - Trends in dacryocystitis in China: A STROBE-compliant article.
AB - The aim of the study was to review the distribution, current trends, and
microbiological characteristics of bacterial pathogens isolated from
dacryocystitis patients in China during the last 15 years.This is a retrospective
multiple-center noncomparative case series. The medical records of 15,452
consecutive patients from 7 cities diagnosed as having dacryocystitis between
2002 and 2016 were reviewed. The patients' demographics, microbiological data,
and antibiotic sensitivity were reviewed and analyzed.A total of 3344 lacrimal
sac content cultures were taken (21.6%) during the study period. A pathogen was
identified in 1996 samples (59.7%), with bacterial isolates accounting for 1902
of the positive cultures (95.3%). Gram-positive isolates, gram-negative isolates,
and anaerobic bacteria were found in 1218 (61.0%), 607 (30.4%), and 285 (14.3%)
samples, respectively. An increase in gram-positive isolates over the study
duration was found (P = .003). The predominant isolates were coagulase negative
Staphylococci (485, 25.5%), Staphylococcus aureus (186, 9.8%), Pseudomonas
aeruginosa (184, 9.7%), and Haemophilus influenzae (152, 9.0%). There was a trend
toward increasing resistance to erythromycin from 10.5% during the first 5 years
of the study to 20.7% during the last 5 years (P < .001). Antimicrobial
susceptibility testing showed that gatifloxacin was the most effective drug
against most of gram-positive, gram-negative, and anaerobic bacteria.The
microbial culture rate of dacryocystitis in China is low. There was an increase
in the percentage of gram-positive bacteria over time. The sensitivity of gram
positive isolates to tested antibiotics is relatively low compared with that of
gram-negative isolates. Our data show that the empiric use of fourth-generation
fluoroquinolones in refractory dacryocystitis may be justified.
PMID- 29953021
TI - Side effects and medication adherence of tyrosine kinase inhibitors for patients
with chronic myeloid leukemia in Taiwan.
AB - Nonadherence is common in patients with chronic myeloid leukemia (CML) and leads
to treatment failure and poor outcomes. Side effects due to treatment are also
common in patients with CML. However, no study has investigated the link between
side effects and medication adherence for patients with CML in Taiwan. Therefore,
the aim of our study was to explore the influence of side effects on medication
adherence in Taiwanese patients with CML.CML in chronic-phase patients treated
with breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1
tyrosine kinase inhibitors were recruited. We designed a questionnaire to collect
baseline patient information, medication adherence (measured using the 8-item
Morisky Medication Adherence Scale), and side effects. Clinical outcomes were
assessed by the 3-month early molecular response rate and the 12-month major
molecular response rate. Statistical comparisons of different parameters between
adherent and nonadherent groups were conducted.Fifty-eight patients were enrolled
in this study, and 31% of them had poor adherence. The lack of information about
treatment and medication was the major reason for poor medication adherence.
Patients who were younger and unmarried were prone to poor adherence. The
occurrence of side effects carried no statistically significant influence on
adherence. Poor adherence resulted in a poor treatment response (lower 3-month
early molecular response rate and lower 12-month major molecular response
rate).Poor adherence is common in Taiwanese patients with CML. The main reason
for a decrease in the adherence rate is the lack of comprehensive information
about treatment and medication, particularly in young and single population. The
next urgent step is to educate patients about their treatment and management of
side effects to improve adherence and treatment outcome for patients with CML in
Taiwan.
PMID- 29953022
TI - Adult severe encephalitis/encephalopathy with a reversible splenial lesion of the
corpus callosum: A case report.
AB - RATIONALE: Clinically mild encephalitis/encephalopathy with a reversible splenial
lesion of the corpus callosum (MERS) is a recently identified clinically and
radiologically distinct syndrome. Clinical symptoms and lesions on the magnetic
resonance imaging (MRI) often disappear in 1 week or a few weeks. However, MERS
manifesting as a severe clinical course with significant sequela has not yet been
reported. PATIENT CONCERNS: A 42-year-old male presented with a 3-day history of
headache, fever, and irrational speech. Physical examination showed a body
temperature of 39.5 degrees C, dysarthria, dyscalculia, recent memory
disturbance, and otherwise normal vital signs. The patient developed status
epilepticus and progressive consciousness disturbance. MRI showed abnormal patchy
signals in the splenium of the corpus callosum. DIAGNOSIS: The clinical feature
and the characteristic of MRI are mostly consistent with MERS. At the same time,
we made a differential diagnosis by testing the NMDARAb, AMPA1Ab, AMPA2Ab, LG1Ab,
CASPR2Ab, GABABRAb in CSF and serum. INTERVENTIONS: The subject was treated with
ganciclovir, antiepileptic, and antipyretic therapy. OUTCOMES: The subject was
living a virtually normal life with persistent mild memory disturbance. MRI
showed that the abnormal signals in the splenium of the corpus callosum had
disappeared, but hyperintensity on T2-weighted and FLAIR imaging was noted in the
centrum semiovale. LESSONS: MERS is a rare clinicoradiological syndrome, which
can manifest as severe symptoms as well. Early diagnosis and treatment should be
emphasized, and the diagnostic value of MRI is highlighted. Clinicians should be
alert to the potential sequela.
PMID- 29953023
TI - Abdominal pain as the presenting symptom of Takayasu arteritis in an adolescent
male: A case report.
AB - RATIONALE: Takayasu arteritis (TA) is a chronic granulomatous inflammation
affecting the aorta and its main branches. The clinical symptoms are mainly due
to arterial claudication and end-organ ischaemia. Abdominal pain is an uncommon
manifestation of TA. PATIENT CONCERNS: We present a rare case of TA in a 13-year
old boy who first presented with abdominal pain. An emergency aortic stent
implantation and aneurysm embolization were performed, and the intra-operative
diagnosis was aortic pseudoaneurysm. DIAGNOSES: A consultation with the
department of rheumatism determined that the diagnosis was Takayasu arteritis
according to the medical history, physical examination and auxiliary examination
results. INTERVENTIONS: The patient was transferred to the department of
rheumatism for treatment with prednisolone and cyclophosphamide. OUTCOMES: Six
months after the initial presentation, he was doing well clinically with no
additional vascular involvement, and his blood pressure had been stabilized with
oral antihypertensive drugs. LESSONS: More detailed examinations of children with
acute abdominal pain should be performed. Abdominal computed tomography (CT)
should be administered, peripheral impulses and arterial bruits should be
checked, and blood pressure among the four limbs should be monitored to rule out
plausible emergencies such as an aneurysm caused by TA.
PMID- 29953024
TI - Metachronous triple primary neoplasms with primary prostate cancer, lung cancer,
and colon cancer: A case report.
AB - RATIONALE: Multiple primary neoplasms (MPNs) are rare. Most MPNs are double, and
triple primary neoplasms are extremely rarer. Here, we describe a case of a 66
year-old man diagnosed with metachronous triple primary neoplasms with primary
prostate cancer, lung cancer and colon cancer. PATIENT CONCERNS: The patient
complained of dysuria in January 2015, and he underwent transurethral resection
of the prostate. The pathological results showed acinar adenocarcinoma of
prostate with a Gleason score of 3+3. In January 2017, he complained of lower
abdominal pain, then he took an enteroscopy examination, found a mass in the
sigmoid colon, and positron emission tomography/computed tomography examination
showed masses in the sigmoid colon and right upper lobe of the lung. Biopsy of
the colon showed moderately differentiated adenocarcinoma with Kirsten rat
sarcoma viral oncogene homolog exon 2 mutation, and biopsy of the lung showed
moderately differentiated adenocarcinoma with epidermal rowth factor receptor
exon 21 mutation. DIAGNOSES: Metachronous triple primary neoplasms with primary
prostate cancer, lung cancer and colon cancer. INTERVENTIONS: The patient
underwent surgical resection of the right upper lobe of the lung, postoperative
stage was T1bN0M0 (stage IA). After 8 cycles of chemotherapy with modified
FOLFOX6 regimen (oxaliplatin 85 mg/m, leucovorin 400 mg/m, 5-fluorouracil 400
mg/m on day 1, followed by 5-fluorouracil 2400 mg/m intravenous infusion over 46
hours every 2 weeks), the patient underwent radical resection of colon cancer,
and he finished the remaining 4 cycles of modified FOLFOX6 regimen chemotherapy
in November 2017. OUTCOMES: The patient takes examination every three months, and
the results show no recurrence. LESSONS: When considering MPNs, thorough
surveillance by new screening methods is required to detect a second or even
third neoplasm at an early stage.
PMID- 29953025
TI - Effect of intraoperative mannitol administration on acute kidney injury after
robot-assisted laparoscopic radical prostatectomy: A propensity score matching
analysis.
AB - Mannitol, an osmotic diuretic, has been used to prevent acute kidney injury
(AKI). However, studies have found divergent effects of intraoperative mannitol
administration on postoperative AKI. We therefore evaluated the effects of
intraoperative mannitol administration on AKI after robot-assisted laparoscopic
radical prostatectomy (RALP) in prostate cancer patients.A total of 864 patients
who underwent RALP were divided into mannitol (administered at 0.5 g/kg) and no
mannitol groups. Demographics, cancer-related data, preoperative laboratory
values, intraoperative data, and postoperative outcomes such as AKI, chronic
kidney disease at 12 months postoperation, duration of hospital stay, and
intensive care unit admission rate and duration of stay were compared between the
2 groups using propensity score matching analysis. To determine the risk factors
for AKI after RALP, univariate and multivariate logistic regression analyses were
performed. Postoperative AKI was defined according to the Kidney Disease:
Improving Global Outcomes criteria.After performing 1:1 propensity score
matching, the mannitol and no-mannitol groups included 234 patients each. The
overall incidence of AKI after RALP was 5.1% and was not significantly different
between the no-mannitol and mannitol groups in the propensity score-matched
patients (13 [5.6%] vs. 11 [4.7%], P = .832). Univariate logistic regression
analysis revealed that body mass index and operative time were associated with
AKI in 864 patients who underwent RALP. However, intraoperative mannitol
administration was not associated with AKI after RALP (P = .284). Multivariate
logistic regression analysis revealed that operative time was significantly
associated with AKI after RALP (odds ratio = 1.013, P = .001). The incidence of
chronic kidney disease (13 [5.6%] vs. 12 [5.1%], P = 1.000) and other
postoperative outcomes were not also significantly different between the no
mannitol and mannitol groups in the propensity score-matched
patients.Intraoperative mannitol administration has no beneficial effect on the
prevention of AKI after RALP in prostate cancer patients. This result provides
useful information for clinical practice guidelines regarding intraoperative
mannitol use.
PMID- 29953026
TI - Administration of low-level laser on muscles of mastication following the
induction of initial fatigue: protocol for a randomized, controlled, clinical
trial.
AB - BACKGROUND: Orofacial pain encompasses painful conditions, such as
temporomandibular disorder (TMD). Multidisciplinary health teams seek to control
such musculoskeletal disorders to improve the quality and functional capacity of
the muscles of mastication. The aim of the proposed study is to evaluate the
effect of low-level laser therapy as a form of treatment for the prevention of
initial fatigue of the muscles of mastication (masseter and anterior temporal
muscles) as well as the recovery of these muscles after induced exhaustion
(caused by isometric contraction) in young adults. METHODS: The participants will
be 78 healthy male and female volunteers between 18 and 34 years of age. The
volunteers will be randomly allocated to a laser group (n = 26), sham group (n =
26), and control group (n = 26). All participants will be submitted to a clinical
evaluation to record mandibular movements, bite force, muscle sensitivity to
palpation, and initial muscle fatigue. Initial fatigue will be induced by
isometric contraction of the jaws. Maximum voluntary contraction will be
performed to record the time until initial exhaustion of the masseter muscle
(determined by electromyography). The groups will then be submitted to the
interventions: active laser therapy (wavelength: 780 nm; fluence: 134 J/cm;
power: 50 mW; irradiance: 1.675 W/cm; exposure time: 80 seconds per point) on 3
points of the masseter and 1 point on the anterior temporal muscles on each side;
sham laser (placebo effect); or no intervention (control). Maximum voluntary
contraction will be performed again after the interventions to record the time
until initial exhaustion of the masseter muscle (determined by electromyography).
Differences in individual time until exhaustion between the pre- and
postintervention evaluations will be measured to determine the effect of low
level laser therapy. DISCUSSION: Although studies have been made with the use of
low-level laser therapy in TMDs and on the effect of photobiomodulation on
fatigue, this the first study to test this therapy in the prevention of fatigue
in this region. The clinical relevance lies in the fact that longer dental
procedures could take place if the patients are less prone to fatigue.
PMID- 29953027
TI - The application of vascularized stomach flap to repair postoperative biliary
stricture.
AB - Hepaticojejunostomy, which is the "gold standard" procedure for repairing
postoperative biliary strictures, predisposes patients to reflux cholangitis from
loss of sphincter of Oddi. The aim of this study was to assess the sphincter
preserving biliary reconstruction approach to repair postoperative biliary
stricture. An autologous vascularized stomach flap was prepared and used to
repair biliary defect caused by postoperative biliary stricture. Patient clinical
data were analyzed retrospectively and long-term prognosis was evaluated based on
the Lillemoe standard. Twenty-eight patients who underwent surgery from 2002 to
2010 were enrolled for the study. The original surgical procedure that caused
biliary stricture consisted of patients having cholecystectomy (n = 22), biliary
duct exploration (n = 5), and hepatectomy (n = 1). Eighteen (64%) of the 28
patients had previous repair surgery before being admitted. Based on the Bismuth
level, 7 were classified as type I, 15 as type II, and 6 as type III. The mean
length of biliary defect determined preoperatively by magnetic resonance
cholangiopancreatography was 1.5 cm. The surgical procedure was successfully
performed for all patients with a mean operation time of 261 +/- 47.8 minutes.
The postoperative complication rate was 10.7%, including minor bile leak (n = 2)
and pulmonary infection (n = 1). There was no perioperative deaths. Two patients
were absent during follow-up, and the remaining 26 patients had a mean follow-up
period of 7.5 years (61-155 months). Twenty-four patients remained healthy during
the follow-up period, while 2 patients (7.7%) had sporadic recurrent cholangitis
that eventually resolved spontaneously. The overall long-term outcome rate was
92.3%. None of the patients had recurrence of stricture during the follow-up
period. These results suggest that biliary repair using vascularized stomach flap
could reduce reflux cholangitis and offer a satisfactory long-term outcome. This
procedure could be a reliable method to repair postoperative biliary stricture
with limited biliary defect.
PMID- 29953029
TI - Associations between serum vitamin D and the risk of female reproductive tumors:
A meta-analysis with trial sequential analysis: Erratum.
PMID- 29953028
TI - An assessment of a pediatric early warning system score in severe hand-foot-and
mouth disease children: To detect clinical deterioration in hospitalized
children.
AB - Identification of deteriorating severe hand, foot, and mouth disease (HFMD)
children for referral to intensive care remains problematic.The medical records
of 2382 hospitalized children with severe HFMD from May 2013 to September 2015
were retrospectively reviewed. A Pediatric Early Warning System (PEWS) score was
designed based on study parameters on admission, evaluated in a logistic
regression model, and subsequently validated with different cut-off scores, to
predict the risk for clinical deterioration.After admission, 191 cases were
transferred to the pediatric intensive care unit (PICU) and 2191 were admitted to
the infectious disease department. Of which, 116 cases were subsequently
transferred to PICU, with younger age, consciousness levels of sluggishness,
lethargy or drowsiness, rashes with vesicles on the hands or feet, moderate or
high fever, increased or disordered lung marking or pulmonary infiltration,
abnormal heart rate, fasting plasma glucose, blood platelet, and C-reactive
protein. A corresponding 10-component PEWS score >7 was significantly associated
with subsequent transfer to PICU.A 10-component PEWS score >7 has good
specificity but poor sensitivity for identifying severe HFMD children vulnerable
to clinical deterioration.
PMID- 29953030
TI - The new reckoning: The Combat Casualty Care Research Program responds to real and
present challenges in military operational projections.
AB - This issue of the Journal of Trauma and Acute Care Surgery features topics from
the 2017 Military Health System Research Symposium and starts a second decade of
partnership between the Combat Casualty Care Research Program (CCCRP) and the
journal. This publication comes at a time of significant change for the CCCRP, as
it responds to military planning for the future multidomain battlefield (MDB).
The projected MDB portends markedly different operational scenarios than those
conducted over the past 17 years. Emerging threats around the globe have the
Department of Defense preparing for more complex battlefields that are larger in
size and scope and which pit the United States against better equipped and more
sophisticated adversaries. As the CCCRP navigates this new reckoning associated
with trauma care on the MDB, its research investments will need to be robust and
enabled to plan, program, and budget for agile and closer-term solutions. To
accomplish this, the program will need to expand on its strong foundation of
lessons learned and assets developed over the past 20 years.
PMID- 29953031
TI - The effects of hemorrhage on the pharmacokinetics of tranexamic acid in a swine
model.
AB - BACKGROUND: The early use of tranexamic acid (TXA) is strongly advocated in
patients who are likely to require massive transfusion to decrease mortality.
This study determines the influence of hemorrhage on the pharmacokinetics of TXA
in a porcine model. METHODS: The investigation was a prospective experimental
study in Yucatan minipigs. First, in vitro plasma-cell partitioning of TXA was
evaluated by inoculating whole blood with known aliquots, centrifuging, and
measuring the supernatant with high-performance liquid chromatography with mass
spectrometry (HPLC-MS). Then, using in vivo modeling, normovolemic and
hypovolemic (35% reduction in blood volume) swine (n = 4 per group) received 1 g
of intravenous TXA and had blood sampled at 14 time points over 4 hours to
determine baseline clearance via HPLC-MS. Additional swine (n = 4) were
hemorrhaged 35% of their blood volume, and TXA was administered as a 15 mg/kg
infusion over 10 minutes followed by infusion of 1.875 mg/kg per hour to simulate
massive hemorrhage scenario. During the first hour of TXA administration, one
total blood volume was hemorrhaged and simultaneously replaced with TXA free
blood. Serial blood samples and the hemorrhaged blood were analyzed by HPLC-MS to
determine the percentage of dose lost via hemorrhage. RESULTS: Clearance of TXA
was diminished in the hypovolemic group compared with the normovolemic group (115
+/- 4 vs 70 +/- 7 mL/min). Percentage of dose lost via hemorrhage averaged 25%.
The lowest measured plasma level during the exchange transfusion was 34 MUg/mL.
CONCLUSION: Mean 25% of the present 2017 Joint Trauma System Clinical Practice
Guideline dosing of TXA can be lost to hemorrhage if a blood volume is transfused
within an hour of initiating therapy. In the case of TXA, which has limited
distribution and is administered during active hemorrhage and massive blood
transfusions, replacement strategies should be developed and tested to find
simple methods of adjusting the current dosing guidelines to maintain therapeutic
plasma concentrations. LEVEL OF EVIDENCE: Therapeutic, level II.
PMID- 29953032
TI - St. John's Wort accelerates the liver clearance of technetium-99-sestamibi in
rats.
AB - BACKGROUND: The intense liver uptake of technetium-99-sestamibi (Tc-MIBI) and
photon scattering from the liver cause problems in quantitative perfusion
interpretation. Hence, Tc-MIBI is a substrate for P-glycoprotein pump; variations
in P-glycoprotein levels may affect liver clearance. METHODS AND RESULTS: Adult
female Wistar rats were divided into seven main groups [control and St. John's
Wort (SJW) treated] and each SJW-treated group included three subgroups that were
killed at 15, 30, and 45 min after Tc-MIBI injection. Treated groups received an
SJW extract suspension at two doses of 100 and 400 mg/kg once daily for 5, 10,
and 14 days, respectively. Tc-MIBI was injected intravenously to all rats 24 h
after the final treatment. The rats were anesthetized at the mentioned time after
tracer injection, and heart and liver tissues were removed, weighed, and their
radioactivity was counted. One rat from each group was selected randomly for
myocardial perfusion imaging. A significant increase in liver clearance and heart
to-liver ratio was observed in all SJW-treated groups compared with the control,
especially at 10 days after SJW treatment. The heart radioactivity decreased in
SJW-receiving groups at 14 days after SJW treatment. CONCLUSION: This study
showed that SJW extract accelerates the liver clearance of Tc-MIBI and
significantly reduces photon scattering from the liver.
PMID- 29953033
TI - Evaluation of Epicardial Fat Thickness in Young Patients With Embolic Stroke of
Undetermined Source.
AB - OBJECTIVES: Epicardial adipose tissue is metabolically active and is an important
predictor of metabolic and cardiovascular diseases. This study investigated the
echocardiographic epicardial adipose tissue measurement in young patients with
embolic stroke of undetermined source (ESUS). MATERIALS AND METHODS: We studied
77 volunteers, including 40 patients with ESUS (mean age 43+/-8 y, 16 female
patients) and 37 healthy subjects (mean age 38+/-7 y, 20 female subjects). All
necessary biochemical parameters were analyzed, and epicardial fat thickness
(EFT) was measured by echocardiography in all subjects. Additional related
diagnostic work-up was conducted in each patient, according to the patients'
clinical presentation. RESULTS: The patients with ESUS had a significantly higher
EFT than the control group (5.51+/-0.82 vs. 3.96+/-0.51; P<0.01). Furthermore,
there was a positive correlation between EFT and serum C-reactive protein levels
(r=0.284; P<0.05). As an optimal cut-off point, a high-risk EFT value of 4.6 mm
was determined to predict ESUS, with an 87.5% sensitivity and an 81.1%
specificity. CONCLUSION: We found that echocardiographic EFT was significantly
higher in young patients with ESUS than in healthy individuals. Increased EFT
might be a novel risk factor in these patients.
PMID- 29953035
TI - Nonaneurysmal Subarachnoid Hemorrhage in Sickle Cell Disease: Description of a
Case and a Review of the Literature.
AB - Descriptions of the natural history of cerebrovascular complications of sickle
cell disease (SCD) characterize ischemic stroke as common during childhood and
hemorrhagic stroke as more common in adulthood. Childhood ischemic stroke is
attributed to vasculopathy with moyamoya syndrome. Hemorrhagic stroke is commonly
attributed to aneurysms accompanying HbSS cerebral vasculopathy in SCD. However,
a growing body of literature highlights multiple contributing factors to
hemorrhagic stroke in children. Primary hemorrhagic stroke is one of the most
devastating neurological complications of SCD. We describe the case of an 18-year
old female affected by HbSS genotype SCD presenting with reversible cerebral
vasoconstriction syndrome (RCVS) as well as features of posterior reversible
encephalopathy syndrome and convexity subarachnoid hemorrhage (SAH) after
transfusion of red blood cells. We reviewed the existing literature dealing with
SCD, blood transfusion, and hemorrhagic strokes. To our knowledge, this case
presentation is unique with convexity SAH predominantly attributable to a RCVS
spectrum disorder occurring in the setting of a recent blood transfusion in an
adolescent female with SCD. As this case illustrates, neurological deterioration
accompanied by intracranial hemorrhage in children and young adults with SCD
after blood transfusion should raise suspicion for RCVS as part of a complex
cerebral vasculopathy. A better understanding of the risk factors leading to
hemorrhagic stroke may help prevent this severe complication in subjects with
SCD. Neuroimaging including angiography in these subjects may enable prompt
diagnosis and management.
PMID- 29953034
TI - Inter-rater Agreement for the Diagnosis of Stroke Versus Stroke Mimic.
AB - BACKGROUND AND PURPOSE: Patients who present emergently with acute neurological
signs and symptoms represent unique diagnostic challenges for clinicians. We
sought to characterize the reliability of physician diagnosis in differentiating
aborted or imaging-negative acute ischemic stroke from stroke mimic. METHODS: We
constructed 10 case-vignettes of patients treated with thrombolysis with
subsequent clinical improvement who lacked radiographic evidence of infarction.
Using an online survey, we asked physicians to select a most likely final
diagnosis after reading each case-vignette. Inter-rater agreement was evaluated
using percent agreement and kappa statistic for multiple raters with 95%
confidence intervals reported. RESULTS: Sixty-five physicians participated in the
survey. Most participants were in practice for >=5 years and over half were
vascular neurologists. Physicians agreed on the most likely final diagnosis 71%
of the time, kappa of 0.21 (95% confidence interval, 0.06-0.54). Percent
agreement was similar across participant practice locations, years of experience,
subspecialty training, and personal experience with thrombolysis. CONCLUSIONS: We
found modest agreement among surveyed physicians in distinguishing ischemic
stroke syndromes from stroke mimics in patients without radiographic evidence of
infarction and clinical improvement after thrombolysis. Methods to improve
diagnostic consensus after thrombolysis are needed to assure acute ischemic
stroke patients and stroke mimics are treated safely and accurately.
PMID- 29953036
TI - A Case Report of Overlapping Miller Fisher Syndrome, Guillain-Barre Syndrome, and
the Bickerstaff Brainstem Encephalitis.
AB - INTRODUCTION: Patients with overlapping Miller Fisher syndrome (MFS), Guillain
Barre syndrome (GBS), and the Bickerstaff brainstem encephalitis (BBE) have
rarely been reported, and the diverse clinical features and sequelae are
challenging for physicians. Through this case report, we present the clinical
course, treatment, recovery, and sequelae of an overlapping MFS, GBS, and BBE
syndrome and provide a review of the literature. CASE REPORT: A 76-year-old woman
was initially presented with diplopia, ophthalmoplegia, and ataxia, but she later
developed weakness of limbs, respiratory failure, deterioration of consciousness,
and cognitive impairment. After IV immunoglobulin and corticosteroid therapy, she
began to recover consciousness and from the weakness from day 18. After 8 months
of rehabilitative therapy, she was able to swallow food without difficulty, but
she still cannot walk without assistance, showed cognitive impairment, and the
tracheostomy remained in place because of persistent respiratory muscle weakness.
CONCLUSIONS: As the clinical course of MFS-GBS-BBE overlapping syndrome is
variable, involving not only the peripheral but also the central nervous system,
the establishment of a comprehensive therapeutic strategy is warranted.
PMID- 29953037
TI - Myelitis and Polyradiculoneuropathy With Severe Pain: Unusual Neurological
Manifestations as Presenting Symptoms of Brucellosis.
AB - Brucellosis, an endemic zoonosis in Portugal, is a multisystem disease,
presenting with neurological manifestations in up to 25% of cases.
Neurobrucellosis diagnostic criteria include evidence of central nervous system
invasion, either by documenting increased blood-brain barrier permeability that
normalizes after treatment or by Brucella isolation. We report 2 patients with
systemic brucellosis presenting with neurological symptoms: A 28-year-old female
with progressive hemiparesis associated with severe refractory thoracic and
lumbar pain, whose spinal magnetic resonance imaging identified longitudinally
extensive myelitis. Brucella agglutination test was positive in blood; however,
cerebrospinal fluid cytochemical, serological testing, and cultures were
negative. A 58-year-old male with intermittent fever in the evening, associated
with severe refractory cervical and lumbar spinal and radicular pain. Blood
workup identified leukocytosis, elevated inflammatory markers and positive
Brucella agglutination test. Cerebrospinal fluid presented mild protein increase
and negative serological testing and cultures. Electromyogram revealed
demyelinating polyradiculoneuropathy. In both cases, antibiotic therapy induced
symptom resolution. Despite the neurological presentation, no evidence of direct
nervous system infection was found. An indirect mechanism appears to be involved,
such as a parainfectious syndrome or circulating endotoxins release by the
bacteria. Brucellosis should be considered in patients presenting with
inflammatory neurological symptoms in endemic regions. Prompt diagnosis and
treatment are important as chronic infection has significant morbidity.
PMID- 29953038
TI - Acute Right Middle Cerebral Artery Occlusion Resulting in Acute Systolic Heart
Failure, Cerebral T-Waves, and QTc Prolongation: A Case Report.
AB - INTRODUCTION: Acute cerebral injuries, such as cerebral ischemic or hemorrhagic
events, have been repeatedly correlated with sudden electrocardiogram (ECG)
changes, such as cardiac arrhythmias, QT prolongation, and T-wave inversion (the
"cerebral T-wave"). Injuries to the insular cortex have been reported in the
literature to result in such changes, possibly due to increased sympathetic tone
to the cardiac system. CASE REPORT: A 65-year-old gentleman presented with an
acute right middle cerebral artery territory infarction, and was found to have
ECG abnormalities and left ventricular dysfunction, which improved after the
acute phase of the stroke. CONCLUSIONS: Acute ischemic infarcts, particularly to
the right insular cortex, can result in ECG abnormalities, such as QT
prolongation and T-wave inversion, as well as acute systolic heart failure; all
of which may be reversible after the acute phase of the stroke.
PMID- 29953039
TI - A Fatal Case of Undiagnosed Candida Meningitis: Role of Computer-assisted
Diagnosis.
AB - Diagnostic error is an increasing health care concern. An intravenous drug abuser
with chronic meningitis died after a prolonged hospitalization from fungal
meningitis diagnosed at autopsy. We examine the diagnostic pitfalls and consider
how a computer-assisted diagnostic system may influence the outcome of an
otherwise fatal condition.
PMID- 29953040
TI - Therapy With Mesenchymal Stem Cells in Parkinson Disease: History and
Perspectives.
AB - BACKGROUND: Parkinson disease (PD) is a neurodegenerative disorder affecting the
basal nuclei, causing motor and cognitive disorders. Bearing in mind that
standard treatments are ineffective in delaying the disease progression,
alternative treatments capable of eliminating symptoms and reversing the clinical
condition have been sought. Possible alternative treatments include cell therapy,
especially with the use of mesenchymal stem cells (MSC). REVIEW SUMMARY: MSC are
adult stem cells which have demonstrated remarkable therapeutic power in
parkinsonian animals due to their differentiation competence, migratory capacity
and the production of bioactive molecules. This review aims to analyze the main
studies involving MSC and PD in more than a decade of studies, addressing their
different methodologies and common characteristics, as well as suggesting
perspectives on the application of MSC in PD. CONCLUSIONS: The results of MSC
therapy in animal models and some clinical trials suggest that such cellular
therapy may slow the progression of PD and promote neuroregeneration. However,
further research is needed to address the limitations of an eventual clinical
application.
PMID- 29953041
TI - Precision's Promise.
PMID- 29953042
TI - What Bed Size Does a Patient Need?: The Relationship Between Body Mass Index and
Space Required to Turn in Bed.
PMID- 29953043
TI - Change in Activities of Daily Living in the Year Following a Stroke: A Latent
Growth Curve Analysis.
AB - BACKGROUND: Early prediction of future functional capability is crucial for
stroke survivors' care management. OBJECTIVES: The purposes of this study were to
test the trajectory of change across time in activities of daily living (ADLs)
and to determine whether the National Institutes of Health Stroke Scale (NIHSS)
score within 24 hours poststroke, gender, and age predict ADLs at 1, 3, 6, and 12
months poststroke. METHODS: A prospective cohort design was used. Baseline
characteristics and neurological deficits were measured in 1,021 stroke
survivors. The 13-item NIHSS was used to examine neurological status within 24
hours poststroke. ADLs were measured with the Barthel index at 1, 3, 6, and 12
months poststroke. A latent growth curve model was used to analyze how the
dynamic changes in ADLs were related to NIHSS score, gender, and age. RESULTS:
The latent growth curve model analyses revealed that, as the time following a
stroke increases, survivors tend to gradually improve with regard to ADLs. In
addition, lower levels of initial ADLs were associated with higher growth in ADLs
over time. However, after 6 months poststroke, further gains in ADLs slowed.
Based on further analysis, the findings indicate that a lower NIHSS score, being
male, and a young age at time of stroke were associated with higher initial
levels of ADLs. Having a higher NIHSS score, being female, and a young age at
time of stroke predicted an increase in ADLs over time. DISCUSSION: To promote
ADLs of stroke patients, NIHSS score at admission, gender, and age should be
included as important predictors of stroke care management. The results highlight
that the rehabilitation of stroke patients should be focused more on ADLs at 1-6
months poststroke.
PMID- 29953045
TI - Healthcare Provider Views on Transitioning from Task Shifting to Advanced
Practice Nursing in Tanzania: Erratum.
PMID- 29953044
TI - Item Generation and Content Validity of the Child-Adolescent Bullying Scale.
AB - BACKGROUND: Healthcare providers do not uniformly screen young patients for
exposure to bullying, and no screening instruments have been developed for
widespread use in clinical settings. OBJECTIVES: The objectives of this study
were to (a) generate scale items by identifying and eliciting concepts relevant
to youths with potential exposure to bullying as well as to professionals who
work with bullied youths and (b) assess the content validity of the new Child
Adolescent Bullying Scale (CABS) instrument. METHODS: A mixed-methods design was
used to develop an initial pool of 52 items. The study was conducted in four
phases: (I) comprehensive review of the existing literature; (II) concept
elicitation through the conduct of focus groups with school-age youths and
professionals who work with bullied youths; (III) concept selection and item
construction; and (IV) content validation assessment of relevance, clarity, and
dimension of each item by a panel of 30 international bullying and measurement
experts through completion of an online survey. RESULTS: An initial pool of 52
potential items was developed during Phases I-III of the study. During Phase IV,
item- and scale-level content validity indices were calculated and were used to
refine the item pool. These strategies resulted in a new, 22-item tool, with
scale-level content validity indices of .954 for clarity and .920 for
representativeness. DISCUSSION: Evaluation of the CABS tool with a sample of
youths drawn from healthcare settings will be necessary to assess the performance
of the CABS items, further evaluate its psychometric properties, and further
refine the tool.
PMID- 29953046
TI - [Dizziness and vertigo associated with vestibular neuronitis: the approaches to
the diagnostics and treatment].
AB - This article is focused on the peculiar features of diagnostics and treatment of
dizziness and vertigo in the patients presenting with vestibular neuronitis. The
authors present the detailed overview of various theories concerning etiology and
pathogenesis of this condition, describe the methods for its clinical and
instrumental diagnostics (including its differential diagnostics from other
diseases associated with acute dizziness and vertigo). Special attention is given
to the methods of pharmacological and physical rehabilitation of the patients
suffering from vestibular neuronitis.
PMID- 29953047
TI - [The peculiar clinical features of different types of acquired cholesteatoma of
the middle ear].
AB - We have undertaken the analysis of the specific clinical manifestations of
acquired cholesteatoma of the middle ear in 437 chronic patients suffering from
this pathology. 96.1% of them presented with primarily acquired cholesteatoma of
the middle ear (including 53.3% having attic cholesteatoma, 22.8% with sinus
cholesteatoma, and 19.9% of tensa retraction cholesteatoma). 3.9% of the patients
exhibited a different mechanism of development of cholesteatoma. The secondary
acquired mesotympanic cholesteatoma formed in association with the long-term
chronic inflammation of the middle ear, concomitant perforation of the tympanic
membrane and epithelial invasion from the edge of the tympanic membrane
perforation and middle ear cavity. Typmanosclerosis of different degree and
localization played an important role in the enhancement of the prevalence of
this condition. All types of acquired cholesteatoma were found to extend beyond
the point of origin of the disorder. The maximum destruction of the ossicular
chain was documented in the patients presenting with sinus cholesteatoma. Those
with secondary acquired cholesteatoma showed the worst functional capacity as a
result of rigid fixation of the auditory ossicles. The overall cholesteatoma
relapse rate (including both residual and recurrent cholesteatoma) was estimated
to be 15.6%. It is concluded that the surgical strategy should be chosen on an
individual basis for each concrete patient. The long-term observation of the
treated patients with the application of the up-to-date radiological techniques
is believed to be the indispensable prerequisite for the successful management of
the complicated pathology under consideration.
PMID- 29953048
TI - [The role of the endoscopic assistance in the surgical treatment of the children
presenting with chronic suppurative otitis media and cholesteatoma].
AB - The present study was designed to elucidate the possibilities for the application
of angled endoscopes in the sanation of those compartments of the middle ear
which are difficult to access for visual control with the use of a microscope,
such as the retrotympanic structures (e.g. tympanic and facial retraction
pockets), anterior epitympanum, etc. To this effect, we have undertaken the
analysis of the results of surgical interventions on the children presenting with
chronic suppurative otitis media and concomitant cholesteatoma. A total of 59
primary operations and 35 secondary ones were performed to treat recurrent
cholesteatoma. In 41 cases, the surgical intervention was carried out without the
endoscopic assistance whereas in the remaining 53 ones the microscopic
observation of the difficult-to-access compartments of the middle ear were
supplemented by the application of an angled endoscope. Whenever residual
portions of cholesteatoma were identified, they were removed under the endoscopic
control. The algorithm for the endoscopic assistance during such operations has
been proposed, its advantages and limitations are considered. It is concluded
that the combination of microscopic and endoscopic techniques for the examination
of and operation on the middle ear creates the conditions for the more reliable
(in comparison with the traditional otomicroscopic methods) removal of the
residual cholesteatoma tissues and thereby allows to reduces the risk of
development of residual cholesteatoma from 25% to 13.5%. The results of the
present study have demonstrated the necessity of development of a universal
approach to the identification of the clinically significant manifestations of
chronic suppurative otitis media and cholesteatoma.
PMID- 29953049
TI - [Asymmetric sensorineural hearing impairment in the adult population].
AB - The relevance of the problem of a sensorineural hearing loss (ASNL) arises from
the necessity of the special approaches to the diagnostics of this condition, the
complications accompanying this pathology, and the difficulties encountered in
the implementation of the methods designed for hearing rehabilitation of such
patients. The objective of the present study was to estimate the prevalence of
ASHL among the adult population. The sensorineural impairment of hearing was
diagnosed in a total of 2456 (72%) examined patients presenting with hearing
loss. To determine the presence of asymmetry of sensorineural hearing loss, we
employed three counting techniques allowing (1) to calculate the difference
between the average hearing thresholds at four frequencies within the range from
0.5 to 4 kHz (the difference was found to be 15 dB or more in 17% of the
patients), (2) to calculate the difference between the degrees of hearing loss in
the right and left ears (the difference was documented in 47% of the patients),
(3) to calculate the difference between the hearing thresholds at least at a
single frequency within the range from 0.125 to 8 kHz (he difference was found to
be 15 dB or more in 71% of the patients). When using the third method to
characterize asymmetry of hearing impairment, it was identified in most patients
(53%) at one or two frequencies. Moreover, there was a large number of the
patients (13%) with asymmetry apparent over the entire frequency range. A high
degree of threshold asymmetry (in excess of 40 dB) was more often noted in the
mid-frequency range. In the majority of the patients, the asymmetry manifested
itself as the different degree of bilateral sensorineural hearing impairment
(51%) or unilateral sensorineural hearing loss with the normal hearing ability
preserved in the contralateral ear (35%). The results of the present study give
evidence of the necessity of developing a reliable method for the identification
of clinically significant ACNL.
PMID- 29953050
TI - [The diagnostics and surgical treatment of the patients presenting with
otosclerosis in the Primorye Territory].
AB - The objective of the present study was to characterize the effectiveness of the
audiological and radiological diagnostic techniques as well as the results of the
surgical treatment of the patients presenting with otosclerosis based at the
hospital clinic of the Pacific State Medical University. The analysis included 49
surgical interventions for stapedoplasty carried out on 42 patients during the
period from 2015 to 2017. The tympanic form of the disorder was diagnosed in
51.02% of the cases, the mixed form I in 16.28%, and the mixed form II in 32.7%.
The excellent results within two months after surgery were obtained in 87.2% of
the treated patients, the good and satisfactory results in 8.72% and 4.08% of
them respectively.
PMID- 29953051
TI - [The role of mono- and binaural hearing aid in the rehabilitation of the adult
patients presenting with hearing impairment].
AB - The objective of the present study was to compare the effectiveness of mono- and
binaural hearing aids in the rehabilitation of the adult patients of different
age presenting with chronic symmetric hearing loss (CSHL). A total of 263
subjects at the age from 50 to 88 years complaining of moderate to severe (grade
I-IV) chronic symmetric hearing impairment were available for the examination.
Following the ENT examination with the application of pure tone audiometry and
impedancometry, the participants of the study were supplied with the individually
fitted digital behind-the-ear hearing instruments and underwent speech audiometry
in the free sound field. The intelligibility of polysyllabic words in the calm
and noisy environment was evaluated. A significant deterioration of the
intelligibility was documented both under the quiet and noisy conditions. Its
severity increased with the patients' age and the degree of hearing impairment.
The comparison of the results of speech audiometry in the patients using either a
single or two hearing aids gave evidence that binaural hearing aids were more
efficient than monoaural ones in 86% of the patients. Re-examination of the same
patients one year after the completion of the first study has demonstrated that
59% of them became permanent users of the hearing aids with 47% of them making
regular use of simultaneously two hearing aids. It is concluded that speech
audiometry in the free sound field can be recommended as a highly informative
method that allows to substantiate the reasonable choice between the mono- and
binaural hearing aids for the adult patients presenting with hearing impairment.
PMID- 29953052
TI - [The importance of the quantitative assessment of the hearing impairment in the
subjects employed under conditions of enhanced noise].
AB - The article describes the domestic modern diagnostic and expert approaches to the
quantitative assessment of the hearing impairment in the subjects employed under
conditions of enhanced occupational noise. It is concluded that the quantitative
criteria for the determination of the severity of hearing loss in the workers of
the 'noisy' professions adopted in this country are comparable with the
respective international standards of and approaches to the medico-social
examination practiced worldwide.
PMID- 29953053
TI - [The treatment of laryngomycosis].
AB - The objective of the present study was to elaborate the therapeutic algorithm for
the treatment of laryngomycosis. We have examined a total of 430 patients
suffering from chronic laryngitis including 100 ones (23.2%) having the fungal
flora. Mycosis was diagnosed by the microscopic study of the stained preparations
with the application of various techniques; moreover, cultivation in elective
nutrient media was used. The yeast-like fungi of the genus Candida were
identified in 98 (98%) and mold fungi of the genus Aspergillus in the remaining 2
(2%) patients. All these 100 patients were given the antifungal treatment. 98 of
them presenting with candidal laryngitis were allocated to three groups. Group A
was comprised of 33 patients who received the local treatment alone, group B
contained 31 patients given only systemic therapy, and group C included 34
patients undergoing the combined treatment with the use of the medications
possessed of both the local and systemic actions. The best clinical results were
obtained in the patients of the latter group in which the therapeutic efficiency
proved to be as high as 79.4%. It is concluded that all the patients suffering
from laryngomycosis are in need of the combined treatment designed to eradicate
the causative agent, restore the vocal function, and achieve the stable remission
of the chronic inflammatory process in the larynx. The combined treatment with
the antimycotic medications exhibiting both the general systemic and local
activities during 3 weeks appears to be the optimal therapeutic modality for the
management of laryngomycosis. Of special importance is the dynamic follow-up of
the treated patients including the control examinations in the course of the
treatment (days 7, 14, and 21) to be followed by the mycological study after the
termination of therapy and its repetition every 3 months during the subsequent
period.
PMID- 29953054
TI - [Optimization of the method for the postoperative treatment following
rhinoplasty].
AB - This article was designed to report the results of analysis of the dynamics of
oedema of the soft tissues of the external nose and the adjacent facial
structures in different periods following rhinoplasty. The metric characteristics
were calculated and the integral index of tissue oedema was determined for 374
patients allocated to two groups. The main group was comprised of 286 (86.5%)
patients who underwent the postoperative rehabilitative treatment making use of
the proposed method. The remaining 88 (23.5%) patients constituted the group of
comparison. The analysis of the data obtained has demonstrated that the
compliance with the newly developed algorithm for the postoperative
rehabilitation permits to considerably reduce the severity of the inflammatory
reaction of the organism to the post-surgical trauma and to shorten the duration
of the postoperative rehabilitation.
PMID- 29953055
TI - [The comparative evaluation of the effectiveness of the treatment of the patients
presenting with the sub-compensated form of chronic tonsillitis making use of the
antiseptic herbal medicinal product in the combination with the standard
conservative therapy: the results of the open randomized study].
AB - The objective of the present study was the comparison of the effectiveness of the
application of tonsilgon-N in the combination with the physical methods for
sanitization of the palatine tonsil lagunes with that of the standard
conservative treatment. A total of 60 patients having the confirmed diagnosis of
sub-compensated form of chronic tonsillitis were recruited to participate in the
study. All the patients were divided into two groups. Group 1 was comprised of 30
patients to whom tonsilgon-N was prescribed for the oral administration (25
droplets thrice daily for 30 days) in the combination with lagune cleansing with
the use of the Tonsillor apparatus during 30 days (a total of 10 procedures).
Group 2 consisted of 30 patients to whom only 10 sessions of rinsing the palatine
tonsil lagunes were prescribed. The inoculums taken from the tonsils of the
patients of group 1 contained no Klebsiella oxytoca, Escherichia coli,
Enterobacter cloacae, and Moraxella catarhalis on the 15th day after the
initiation of the treatment whereas the presence of the persisting pathogenic
bacterial species was documented in 23.3% of the patients of this group. 10% of
the patients in group 2 were found to retain Klebsiella oxytoca, Enterobacter
cloacae, and Moraxella catarhalis in their tonsils whereas the rate of isolation
of the pathogenic biotope amounted to 36,6%.
PMID- 29953056
TI - [The rhinological simulator: the upgrade and validation study with the evaluation
of the effectiveness of its application].
AB - The objective of the present study was to upgrade the rhinological simulator
employed as a tool for the teaching of the basic technical skills in endoscopic
sinus surgery (ESS). The new ESS simulator providing a model of the nasal cavity
consists of the replaceable cylinders and the adaptable table stand. It includes
a set of 3D printed nasal models. Each of them is the elliptical tube of a
specific size. The participants of the study performed different tasks depending
on the structural properties of the tubes. A wide variety of surgical instruments
and esndoscopes could be fitted to the simulator. 16 otorhinolaryngologists
having no previous experience with ESS were recruited into the study to evaluate
the effectiveness of the training procedures. After a brief tutorial, the
participants practiced an one hour-long exercise per day during 5 days. The pre
training and post-training performances were videotaped. The task-performance
time and the number of technical errors made by the operators were estimated
immediately before and after the training session. To assess the subjective
attitudes of the operators toward the new technology, the participants of the
study were asked to complete the model questionnaire soon after the termination
of the training course. The questionnaire contained 34 items. The correctness of
the answers was assessed based on the 5-point Likert scale, with score 1 meaning
'totally disagree' and score 5 - 'totally agree'. The statistically significant
reduction of the performance time and the number of technical mistakes was
documented within the first 5 hours after the onset of teaching (p<0.05) which
suggests the effectiveness of the training procedures. The questionnaire study
has demonstrated the positive attitude of the trainees toward the proposed
technology. The average score based on the Likert scale was higher than 3 for all
kinds of questions. It is concluded that the results of this study give evidence
of the positive assessment of the upgraded rhinological simulator as an effective
tool for the teaching of the basic skills necessary to operate various surgical
instruments and endoscopes by the novice surgeons in the field of endoscopic
sinus surgery .
PMID- 29953057
TI - [Allergic rhinitis: the modern aspects of therapy].
AB - The main objectives of the present article were to systematize the modern views
of the causes and risk factors of allergic rhinitis, to clarify the manner of its
development, to define the leading etiological mechanism underling the
pathogenesis of this condition, to consider the methods used for the diagnostics
and the treatment of this disease, and to sum up the clinical experience with the
use of Levocetirizine (Allerwey) for the management of allergic rhinitis. Special
attention is given to the achievement and the maintenance of control of the
persistent or intermittent forms of allergic rhinitis and to approaches to its
treatment based on the medications registered in the Russian Federation.
PMID- 29953058
TI - [The role of microbiota in chronic pharyngitis].
AB - This article describes the modern approaches to the diagnostics and treatment of
fungoid conditions of the pharynx with special reference to the main methods for
the detection of pharyngomycosis and its clinical manifestations based on the
results of analysis of the investigations carried out during the period from 2012
till 2016. Among the 3,465 patients presenting with chronic inflammatory
pathology of the pharynx who sought medical advice and treatment at the clinical
departments of the Institute, 861 ones (25%) were found to have mycotic lesions
of the pharynx. Erythematous (atrophic) chronic pharyngitis was the predominant
form of the disease documented in 2,059 patients whereas the remaining 1, 406
ones presented with the hypertrophic forms. The fungal infection was diagnosed in
403 (19,5%) patients with erythematous atrophic chronic pharyngitis in comparison
with 458 (32,5%) patients suffering from the hypertrophic forms of this pathology
including pseudomembranous, hyperplastic (granulomatous), and erosive-ulcerative
ones. The principal pathogenic agents responsible for the development of fungal
pharyngitis in our patients were fungi of the genus Candida that accounted for 97
- 99% of all the cases of this disease. The currently available modalities for
the treatment of pharyngomycosis are described.
PMID- 29953059
TI - [An acute acoustic injury during the early postoperative period following
stapedoplasty].
AB - This article was designed to report a clinical case of an acute acoustic injury
inflicted by a discharge of the lightning ball during the early postoperative
period in a female patient following surgical stapedoplasty. The acoustic impact
resulted in a marked deterioration of hearing in the operated ear with
simultaneous elevation of the threshold of bone sound conduction to above the
preoperative value. It is concluded that the patients who had undergone the
stapedoplastic surgical intervention should be advised to avoid strong acoustic
impacts during the postoperative period.
PMID- 29953060
TI - [Adenoid cystic carcinoma of the larynx: a case report].
AB - Adenoid cystic carcinoma is one of the rare pathological conditions affecting the
larynx. It is known to develop from the glandula elements present in this organ.
The authors report a clinical observation of adenoid cystic carcinoma in the form
of an exophytic tumour of the pale pink colour having a smooth surface and the
well-pronounced vascular patterns at the base. The neoplasm is localized in the
arytenoid and retroarytenoid cartilage regions. Being of 3.5-4 cm in size, the
tumour causes the narrowing of the larynx in its posterior portions and restricts
its mobility. Bearing in mind the considerable extension of the neoplastic
process, we undertook laryngectomy including the resection of the
orolaryngopharynx and the cervical portion of the oesophagus, the subtotal
resection of the thyroid gland and the simultaneous reconstruction of the
orolaryngopharynx.
PMID- 29953061
TI - [The injuries to the nose and paranasal sinuses in the children resulting from
shooting an air rifle].
AB - This article reports two clinical cases of the successful treatment of the
gunshot wounds in the nasal cavity and paranasal sinuses of the children
resulting from the careless use of the pneumatic weapons. Despite the fact that
the shots were fired from a close distance, the intracranial structures and the
eyeballs remained unaffected. The bullets were localized in the nasal septum of
one child and in the frontal recess of the other as is typical of the injuries
inflicted to the nose and paranasal sinuses by the shots from the air rifles.
Multi-slice spiral computed tomography (MSCT) is known to have a number of
important advantages over the roentgenological examination for determining the
location of the bullets. Bullets for pneumatic rifles are manufactured in the
form of the balls either from lead or copper-coated steel; therefore, they are a
priory can not be removed with the use of a magnet.
PMID- 29953062
TI - [The wounds of the neck].
AB - The author presents his personal observation of a complex wound on the neck
treated with a favourable outcome. Prior to the surgical intervention, the
efficient intubation was performed by an anesthesiologist through the wound at
the frontal surface of the neck which communicated with the cavity of the
oropharynx. The revision showed the injury to the superior thyroid artery
branching off from the external carotid artery. Ligation of the vessel did not
cause the deterioration of cervical circulation. The long-term hemostasis was
achieved, Thereafter, the mid-tracheostomy was performed and the nasogastric tube
installed. The wound was copiously washed with an antiseptic solution. The layer
by layer suturing of the mucous membrane of the oropharynx was carried out. The
hyoid bone was sutured to the soft tissues of the floor of the mouth, and the
oropharynx was reconstructed. The soft tissues were juxtaposed and sutured. The
rubber graduates were removed on day 3 after the termination of the surgical
intervention. The tracheostomy tube and nasogastric tube were removed on the 7th
day and the 10th day after surgery respectively. The wound healed by primary
intention. The patient was discharged from the hospital in the satisfactory
condition on the 14th postoperative day.
PMID- 29953063
TI - [The patulous Eustachian tube syndrome: the current state-of-the-art and an
original clinical observation. Second communication].
AB - The choice of the treatment strategy for the patients presenting with the
patulous Eustachian tube syndrome constitutes a serious challenge for an
otorhinolaryngologist. Despite the considerable progress achieved during the past
years in the development of modern pharmacotherapy and functional endoscopic
surgery, the specialists often encounter difficulties in the management of the
patients suffering from this disease. The present article (continuing the
previous communication) contains information concerning the historical and modern
approaches to the treatment of the patients with the patulous Eustachian tube
syndrome. The authors describe the conservative and surgical methods employed for
the treatment of this condition and the approaches to the choice of the treatment
strategies depending on the etiology, pathogenesis, and severity of the disorder
being considered, its duration, and the character of the morphological changes
identified during the diagnostic procedures. The authors emphasize the importance
of the wait-and-see strategy for the treatment of the patients presenting with
the patulous Eustachian tube syndrome. In conclusion, they present the concrete
results of four original observations of such patients.
PMID- 29953064
TI - [The diagnostics and treatment of tympanophonia].
AB - Tympanophonia can be a consequence of a variety of diseases and pathological
conditions diagnostics of which encounters difficulties. The comprehensive
clinical examination of the patient is necessary to determine the cause of
tympanophonia including elucidation of the following characteristics: initial
(acute or gradual) sensation of sound in the ear(s), duration of persisting
clinical manifestations, the presence of an acoustic or craniocerebral injury,
characteristics of the noise, viz. continuous or intermittent, clicking sounds,
paroxysmal or pulsed noise (synchronous with the heart beating), fluctuating,
audible to the patient alone or to the surrounding people as well, unilateral and
bilateral noises (either symmetric or asymmetric), perception of noise in the
head rather than ears., high- and low-pitched noise together with the
accompanying neurological symptoms. The analysis of these characteristics makes
it possible to differentiate between objective and subjective sensation of noise
in the ear(s), determine the amount of additional studies needed for the
evaluatio of the conditions of a given patient, identify the possible cause of
tympanophonia, establish the nosological diagnosis, and distinguish a group of
the patients in need of emergency otological management.
PMID- 29953065
TI - [The multidisciplinary approach to the diagnostics and surgical treatment of the
lacrimal passages].
AB - The primary objective of the present study was to highlight the current state of
research on the pathology of the lacrimal organs based on the results of the
analysis of the relevant publications in the domestic and foreign scientific
literature. Special attention in this review is given to the problems of
diagnostics, indications for the probing, the treatment and stenting strategies.
The authors report their original observations contributing to the better
understanding of the anatomical features of the nasolacrimal passages. In
addition, the data on the principal pathogenic agents are presented together with
certain peculiarities of the surgical treatment of the pathology under
consideration.
PMID- 29953066
TI - [The possibilities for the prevention of incompetent tracheorrhaphy].
AB - The present review of the literature is focused on the methods designed for the
prevention of incompetent tracheorrhaphy. The main cause that dictates the
necessity of strengthening the sutures is the risk of the development of the
complications during the postoperative period following the surgical
interventions. The incompetence of the tracheal anastomoses is known to occur in
3.6-26.3% of the patients which leads to the development of such complications as
neck phlegmon, mediastinitis, and pleural empyema. The mortality rate amounts to
18.2%. The authors describe the methods employed for the prevention of
incompetent tracheorrhaphy following the circular resections and suturing of the
linear traumatic defects. The advantages and disadvantages of individual methods
are discussed.
PMID- 29953077
TI - [Role of optical coherence tomography angiography in diagnostics of early
choroidal melanoma and circumscribed choroidal hemangioma].
AB - : Small choroidal melanoma is a malignant tumor that is prone to early
metastasis, its amelanotic form is often similar to circumscribed choroidal
hemangioma. The main attribute for tumor identification is its vascularization,
which is the target of various examination methods. Optical coherence tomography
angiography (OCTA) has not been previously used in complex diagnostics of early
choroidal melanoma and circumscribed choroidal hemangioma for detection of tumor
vessels and the nature of their branching, as well as for vessel caliber
comparison. Purpose to examine vascularization of early uveal melanoma and
circumscribed choroidal hemangioma by optical coherence tomography angiography.
MATERIAL AND METHODS: The study included 23 patients with early choroidal
melanoma (13 subjects) and circumscribed choroidal hemangioma (10 subjects) that
were examined by optical coherence tomography angiography. According to
ultrasound investigation, mean tumor prominence was 1.1+/-0.3 mm, mean base
diameter - 8.1+/-0.6 mm. RESULTS: Optical coherence tomography angiography in 13
patients with small choroidal melanoma revealed presence of a neovascular
component localized under retinal pigment epithelium (RPE) that had marginal
avascular zone corresponding to the tumor slope. The loop-like shape of tumor
vessels with numerous twists and interweaving was noted under retinal vessels. A
tree-shaped neovascular component with large-caliber vessels in the form of a
tree trunk with multiple branches extending from it was seen under RPE in 4 cases
with circumscribed choroidal hemangioma; diffuse vascularization in the form of
numerous tiny tortuous vascular branches was seen in 6 patients. CONCLUSION:
Optical coherence tomography angiography allows detection of tumor's own vessels
with characteristics of their vascularization in early choroidal melanoma and
circumscribed choroidal hemangioma. Increasing the frequency of detection of
tumor's own vessels will make possible early differential diagnostics of a
malignant or benign tumor and will help establish adequate conserving therapy.
PMID- 29953078
TI - [Pattern visual evoked potentials and their relation to the peripapillary and
retrobulbar blood flow in glaucoma].
AB - PURPOSE: To examine the relationship between the development of bioelectric
response of retinal cell elements to pattern stimulus and the ocular blood flow.
MATERIAL AND METHODS: Electrophysiological studies, including pattern-reversal
visual evoked potentials (VEP) with large 1 degree (1 degrees ) and small 0.25
degrees checks, Color Doppler imaging (CDI) of the retrobulbar vessels, and OCT
Angiography in the area of the optic disc and peripapillary retina were performed
in 48 patients with initial primary open-angle glaucoma (POAG), 47 patients with
advanced POAG, and 42 control subjects. Authors also studied the correlations
between VEP values and the parameters used in CDI and OCT-A examination. RESULTS:
The most noticeable differences between the study groups were the amplitudes of
P100 pattern VEP values for small and large patterns and the OCT-A parameters:
Whole-image Disc Vessel Density (widVD), Peripapillary Vessel Density (pVD),
Peripapillary Vessel Density Inferior Temporalis (pVD IT). In initial glaucoma, a
strong correlation was observed between the amplitude of P100 pattern VEP 1
degrees and pVD IT (r=0.75; p<0.0001); the blood flow rates in ophthalmic
artery, central retinal artery, central retinal vein and short posterior ciliary
arteries were below normal, while the blood flow in these vessels had
statistically reliable correlation with the amplitude of P100 pattern VEP
(p<0.05). No correlation was found in patients with advanced stages of glaucoma.
CONCLUSION: Pattern VEP is an informative method of glaucoma diagnostics which
accuracy can be enhanced by combining it with OCT-A blood flow examination.
PMID- 29953079
TI - [Late results of phaco-canaloplasty in patients with concomitant advanced
pseudoexfoliation glaucoma and cataract].
AB - PURPOSE: To assess the safety and efficacy of phaco-canaloplasty in patients with
concomitant advanced pseudoexfoliation glaucoma and cataract. MATERIAL AND
METHODS: The study included 56 patients (57 eyes) who underwent phacoanaloplasty
guided by Glaucolight microcatheter. All patients were followed up for 48 months.
Visual acuity, changes of intraocular pressure (IOP), use of glaucoma
medications, incidence of complications, as well as postsurgical interventions
were examined. RESULTS: Mean preoperative IOP decreased significantly from 29.8
mmHg (15.8-61.6) with a mean of 1.92 (0-3) glaucoma drops to 12.9 mmHg (11.0
19.6) with a mean of 0.12 (0-3) drops respectively 48 months after
phacocanaloplasty. Mean visual acuity increased from preoperative 0.15 (0.01-0.8)
to 0.6 (0.01-1.2). The most frequent complications included intraoperative
perforation of Descemet's membrane (4 eyes, 7%) and hyphema (37 eyes, 65%), IOP
spikes (4 eyes, 7%) and inflammation (4 eyes, 7%) in the early postoperative
period. CONCLUSION: Phacocanaloplasty in eyes with concomitant advanced
pseudoexfoliation glaucoma and cataract re-establishes the natural outflow system
and leads to significant IOP reduction with minimal risk of intra- and
postoperative complications.
PMID- 29953080
TI - [Predicting the probability of development and progression of primary open angle
glaucoma by regression modeling].
AB - : Prediction of the clinical course of primary open-angle glaucoma (POAG) is one
of the main directions in solving the problem of vision loss prevention and
stabilization of the pathological process. Simple statistical methods of
correlation analysis show the extent of each risk factor's impact, but do not
indicate the total impact of these factors in personalized combinations. The
relationships between the risk factors is subject to correlation and regression
analysis. The regression equation represents the dependence of the mathematical
expectation of the resulting sign on the combination of factor signs. PURPOSE: To
develop a technique for predicting the probability of development and progression
of primary open-angle glaucoma based on a personalized combination of risk
factors by linear multivariate regression analysis. MATERIAL AND METHODS: The
study included 66 patients (23 female and 43 male; 132 eyes) with newly diagnosed
primary open-angle glaucoma. The control group consisted of 14 patients (8 male
and 6 female). Standard ophthalmic examination was supplemented with biochemical
study of lacrimal fluid. Concentration of matrix metalloproteinase MMP-2 and MMP
9 in tear fluid in both eyes was determined using 'sandwich' enzyme-linked
immunosorbent assay (ELISA) method. RESULTS: The study resulted in the
development of regression equations and step-by-step multivariate logistic models
that can help calculate the risk of development and progression of POAG. Those
models are based on expert evaluation of clinical and instrumental indicators of
hydrodynamic disturbances (coefficient of outflow ease - C, volume of intraocular
fluid secretion - F, fluctuation of intraocular pressure), as well as
personalized morphometric parameters of the retina (central retinal thickness in
the macular area) and concentration of MMP-2 and MMP-9 in the tear film.
CONCLUSION: The newly developed regression equations are highly informative and
can be a reliable tool for studying of the influence vector and assessment of
pathogenic potential of the independent risk factors in specific personalized
combinations.
PMID- 29953081
TI - [Determination of intralenticular pressure in patients with intumescent
cataract].
AB - : When the lens swells, a liquefied lenticular substance that increases
intralenticular pressure accumulates in the lens bag making it difficult to
perform standard capsulorhexis. Thus, determination of the intralenticular
pressure value is of great importance for safe intumescent cataract
phacoemulsification. PURPOSE: To develop a technology for intralenticular
pressure measurement in patients with intumescent cataract and to construct a
mathematical model for its prognosis according to preoperative examination data.
MATERIAL AND METHODS: Intralenticular pressure was measured in 11 eyes with
intumescent cataract. Before that, the following parameters of the anterior
compartment of the eye were examined: anterior chamber depth, lens thickness
according to ultrasound biomicroscopy (UBM), hypoechogenic layer (the anterior
layer of liquefied lenticular masses), equatorial angle. RESULTS: The
intraoperative technology of the intralenticular pressure measurement was
developed. The direct dependency between thickness of the swelling lens,
hypoechogenic layer value (the anterior layer of liquefied lenticular masses),
anterior chamber depth and intralenticular pressure magnitude was defined.
CONCLUSION: For the first time, the intraoperative intralenticular pressure was
measured in patients with intumescent cataract. A dependency was defined between
the thickness of the lens and the anterior layer of liquefied lenticular masses,
anterior chamber depth, and intralenticular pressure magnitude; based on this, a
mathematical model for intralenticular pressure measurement was constructed.
PMID- 29953082
TI - [Reducing cytotoxic action of the preservative employed in ophthalmic hypotensive
medications with tear replacement therapy].
AB - PURPOSE: to assess the possibilities of reducing the cytotoxic effect of
benzalkonium chloride (a preservative used in ophthalmic hypotensive drugs) with
the help of tear replacement therapy. MATERIAL AND METHODS: The study included 28
patients (56 eyes) who had been using antiglaucomatous drugs containing
benzalkonium chloride as a preservative for various periods (from 2 months to 17
years). The examination was performed in the setting of compensated IOP. In
addition to hypotensive topical medication regimen, all patients were prescribed
Stilavit eye drops. Subjects were examined prior to the prescription of
artificial tears and after 1, 3 and 6 months of its usage. Effectiveness of the
treatment was evaluated with biomicroscopy, Norn's test, Jones test, tearscopy,
OCT-meniscometry, confocal microscopy, and impression cytology. RESULTS: The use
of 'Stilavit' artificial tears in combination with antiglaucoma drugs led to an
improvement of the corneal epithelium condition in 85% of cases, a statistically
significant increase in the mean values of precorneal tear film rupture time
after 1, 3 and 6 months by 26%, 61.2% and 85.8% respectively. Maximum increase of
main tear production level was achieved after 3 months of treatment (increased by
43.5%), and was accompanied by 18.6% rise of the lower tear meniscus height after
3 months; in 6 months it raised by 29.4%. A tendency for restoration of the lipid
layer of the tear film was observed. According to confocal microscopy and
impression cytology, positive dynamics in the condition of corneal epithelium and
conjunctival epithelial layer were present. CONCLUSION: The study results justify
the use of tear replacement therapy, in particular the tear substitute Stilavit,
as an additional protective agent for glaucoma treatment regimen.
PMID- 29953083
TI - [Complex morphological assessment of anterior capsule of the lens in patients
with capsular contraction syndrome (a clinical case study)].
AB - : The anterior capsular contraction syndrome (ACCS) in pseudophakic patients is
known to be accompanied by postoperative opacity of anterior lens capsule (ALC)
and partial or full closure of anterior capsulotomy opening. PURPOSE: To perform
complex morphological assessment of ALC in patients with ACCS. MATERIAL AND
METHODS: The study involved complex analysis of ALC that was removed due to ACCS
in the pseudophakic eye in the setting of diabetes mellitus and past
vitreoretinal surgery. The following examination methods were used: light-optical
microscopy of ALC samples in the form of polychrome-colored semifine sections
using optical microscope Leica DM-2500 (Germany), scanning microscopy of ALC
surface with EVO LS10 (Carl Zeiss, Germany) microscope, analysis of chemical
element composition and its variation of the ALC sample with energy-dispersive
spectrometer Oxford X-Max50 (Oxford, UK). RESULTS: Light-optical microscopy
showed altered state and plication of ALC induced by proliferation from inner
surface of the fibrocellular tissue, which gradually thickens (up to 360 um)
towards center and causes reduction of anterior capsulotomy opening. Scanning
electron microscopy revealed presence of tissue with uneven micro-relief and a
porous three-dimensional structure uncharacteristic for capsule on the surface of
ALC. Thickness of the fibrous deposition significantly exceeded the thickness of
ALC. Evaluation of elemental composition of the fibrocellular tissue showed
elevated concentration of sulfur and phosphorus, which indicates high activity of
the regenerative process. In the observed case, the regenerative process was of
substitute nature because an attempt to restore the lens was accompanied by
formation of connective tissue structurally different from original. CONCLUSION:
Complex assessment of an isolated ALC sample allowed revelation of the chain of
pathological processes accompanying the development of ACCS.
PMID- 29953084
TI - [Femtosecond laser-assisted cataract surgery and conventional phacoemulsification
cataract surgery in patients with lens subluxation].
AB - PURPOSE: To analyze the results of femtosecond laser-assisted cataract surgery
(FLACS) and conventional phacoemulsification cataract surgery (CPCS) in patients
with 1-2 degree lens subluxation. MATERIAL AND METHODS: The follow-up involved 86
patients (89 eyes). The 1st group comprised 34 patients (35 eyes) that underwent
FLACS; the 2nd group included 52 patients (54 eyes) who underwent CPCS. RESULTS:
At day four of the follow-up central corneal thickness was significantly lower
after FLACS (pm-u=0.024), but the difference did not remain statistically
reliable by 1.5 months after the surgery. At discharge day and 4 months after the
surgery uncorrected visual acuity (UCVA) after FLACS reliably exceeded UCVA of
the 2nd group patients (pm-u=0.00) with mean UCVA being 0.61+/-0.29 and 0.42+/
0.25 respectively. Internal higher order aberrations (HOA) in 5.0 mm zone in the
1st group decreased by 4 times and amounted to 0.236+/-0.06 MUm, in the 2nd group
increased by 4.1 times and was 4.606+/-8.16 MUm; the difference between the
groups was statistically significant (pm-u<0.001). Mean endothelial cells density
after FLACS was 2551.91+/-321.55 cells/mm2, after CPCS - 2352.35+/-436.68
cells/mm2 (pm-u<0.005). Complications after FLACS included 2 cases (5.71%) of
posterior capsular rupture and 1 case (2.8%) of post-op corneal edema; patients
after CPCS had 6 (11.1%) and 12 (22.2%) complication cases respectively.
CONCLUSION: FLACS is the safer and more effective surgery choice for patients
with 1-2 degree lens subluxation in comparison with CPCS; it decreases the risk
of possible complications and provides faster postoperative rehabilitation.
PMID- 29953085
TI - [Serous retinal detachment after phacoemulsification with intracameral cefuroxime
(a case-control report)].
AB - : Serous retinal detachment is a rare postoperative complication of
phacoemulsification with intracameral antibiotics. Diagnostic and therapeutic
strategy in such cases is not well known. PURPOSE: To present a case of serous
retinal detachment after phacoemulsification with intracameral cefuroxime.
MATERIAL AND METHODS: A retrospective analysis of the medical record of one
patient who had underwent cataract phacoemulsification on both eyes; the follow
up period was 5 months. RESULTS: Phacoemulsification of noncomplicated cataract
with implantation of intraocular lens in the right eye was completed
uneventfully; 1 mg of cefuroxime was administered into the anterior chamber at
the end of the surgery. In the first day after the surgery visual acuity
decreased to 0.2. Serous detachment of retinal pigment and sensory epithelia in
the macula area was revealed by optical coherence tomography (OCT). Fluorescein
angiography showed no pathological vascular activity. The patient received
standard post-surgery therapy supplemented with subtenon triamcinolone,
intravenous dexamethasone injections and systemic acetazolamide ingestion. The
retinal detachment status was monitored daily by OCT. By day 6 of the follow-up
visual acuity recovered to 1.0. After 5 months, inner retinal profile deformation
was revealed. The patient's left eye was considered the 'control' eye;
phacoemulsification without cefuroxime was performed on it 5 months after the
initial surgery, and no complication occurred during the follow-up. CONCLUSION:
Serous detachment of retinal pigment and sensory epithelia during the early
postoperative period after cataract surgery may be caused by a toxic reaction to
intracameral cefuroxime even when it's administered in standard dosage. This
complication has a favorable prognosis, but requires long term monitoring.
PMID- 29953086
TI - [Multi-session stereotactic radiotherapy in the treatment of recurrent B-cell
primary intraocular lymphoma (a case report)].
AB - The article describes the clinical observation of a 41-year-old woman suffering
from non-Hodgkin's B-cell primary lymphoma of the central nervous system
involving both eyes. The article features the data on 85-month follow-up, as well
as description of the clinical and instrumental features of the disease. The
study provides analysis of the long-term results of combined treatment of
recurrent primary intraocular lymphoma including repeated courses of radiation
therapy.
PMID- 29953087
TI - [Dome-shaped macula: features of differential diagnostics with clinical
examples].
AB - : The phenomenon of dome-shaped macula (DSM) constitutes protrusion of membranes
of the posterior pole of the eye toward the vitreous body due to local thickening
of sclera layers. The phenomenon was detected using enhanced depth imaging
optical coherence tomography (EDI-OCT). In uncomplicated forms of DSM, all layers
of the retina are contiguous, but the setting of DSM can involve a number of
pathological conditions causing decrease in vision. One of the most often
described concurrent conditions in DSM is serous retinal detachment (SRD). Such
complicated forms of DSM are often masked as a non-pigmented neoplasm of the
choroid, in particular hemangioma (HC). PURPOSE: To demonstrate the possibilities
of differential diagnostics of DSM with HC using modern instrumental diagnostic
methods. MATERIAL AND METHODS: The study involved two clinical cases of patients
with DSM and HC, who underwent comprehensive ophthalmological examination
including EDI-OCT and OCT angiography, fluorescent angiography (FA), indocyanine
green angiography (ICG) and magnetic resonance imaging of brain and orbits (MRI).
RESULTS: The most simple and highly informative method for differential
diagnostic of DSM with HC is currently EDI-OCT. In difficult differential
diagnostic cases, it is recommended to use FA and MRI. Additionally, for
identification of the cause of SRD in DSM, OCT-angiography and ICG-angiography
can be used. Thus, diagnostics of DSM is difficult today primarily because of the
low awareness of ophthalmologists about the presence of such macula pathology.
Detection of this anatomical feature by means of ophthalmoscopy alone can be
difficult and requires special skills and experience. The use of EDI-OCT, as well
as FA and MRI in difficult differential diagnostic cases, and correct
interpretation of the obtained data can help avoid diagnostic errors.
PMID- 29953088
TI - [Surgical technique of retropupillary iris-claw fixated IOL reimplantation].
AB - : Prevention and treatment of cataract surgery complications in patients with
lens subluxation remains one of the current problems of phaco surgeries. PURPOSE:
To develop and to test the surgical technique for reimplantation of in-the-bag
dislocated intraocular lenses (IOL) or sulcus-fixated IOL. MATERIAL AND METHODS:
Surgical outcomes of 150 patients (150 eyes) with in-the-bag IOL dislocation (122
eyes) or sulcus fixated IOL dislocation (28 eyes) were analyzed. The follow-up
period lasted 1-3 years. RESULTS: In all cases the dislocated IOL was removed and
retropupillary iris-claw 'Artisan' IOL implantation was performed. After the IOL
exchange, visual acuity improved in all patients, while the fixation of
retropupillary IOL remained stable. CONCLUSION: This surgical technique of
dislocated IOL exchange coupled with retropupillary implantation of 'Artisan' IOL
provides reliable anatomic and functional results.
PMID- 29953089
TI - [Treatment of postoperative macular edema (a clinical case study)].
AB - Pseudophakic cystoid macular edema (CMO) known to appear in 0.1-2.35% of patients
after phacoemulsification is one of the common causes of vision decrease during
postoperative period. The authors analyzed a case of CMO development in a
pseudophakic patient diagnosed 7 months after uncomplicated phacoemulsification.
Optical coherence tomography (OCT) was suggested for patients with low vision and
a sensation of shroud before the eye for early diagnosis of pathological process.
Intravitreal injection of the 0.7 mg dexamethasone micro-implant performed soon
after establishing the diagnosis was proved to be viable for postoperative CMO
arrest in patients without previous treatment. One month after intravitreal
implant injection, the visual acuity in the patient's eye improved from 0.4 to
0.7, and retinal thickness in the macular area decreased from 705 to 255 MUm. The
result remained stable for 10 months. Intravitreal micro-implant appeared to have
higher efficiency in contrast with traditional treatment methods (according to
literature data), which was attributed to direct drug delivery to the area of
pathological process. The use of 0.7 mg dexamethasone implant did not increase
the intraocular pressure indicating its potential viability for patients with
compensated glaucoma.
PMID- 29953090
TI - [Molecular genetic examination for dry eye syndrome prognosis].
AB - The article reviews the results of Russian and foreign studies concerning the
search of susceptibility genes for widespread multifactorial diseases: Sjogren's
syndrome and rheumatoid arthritis. Studying regularity patterns of genome changes
in autoimmune processes with ophthalmic manifestations and their correlation with
the severity of dry keratoconjunctivitis will contribute to a better
understanding of the etiology and pathogenesis of eye manifestations of the
diseases, and will also allow the development of new effective methods of
diagnosis and targeted therapy.
PMID- 29953091
TI - [Ophthalmic manifestations of facial nerve palsy].
AB - Facial nerve palsy is a common pathology that develops due to various diseases,
traumas and medical interventions. The most common peripheral type of facial
paralysis leads to acute unilateral involvement of facial muscles along with the
development of paralytic lagophthalmos. The absence of adequate and timely
medical treatment in patients with paralytic lagophthalmos can lead to severe
corneal complications such as cornea perforation causing loss of eye and
consequently restricted professional ability, work capacity and significant
decrease of patient's life quality. Patients with paralytic lagophthalmos require
timely, complex, planned treatment involving various correction methods aimed at
protection of the cornea, as well as anatomical and functional recovery of the
eyelids. Chemodenervation of the upper eyelid muscles is a pathogenetically
substantiated method that can help restore the protective function of the upper
eyelid and prevent corneal complications; it can be recommended for early stages
of the disease.
PMID- 29953092
TI - [Ophthalmic Rosacea: etiopathogenesis and modern treatment methods].
AB - Rosacea is a multifactorial chronic inflammatory disease with various clinical
manifestations. Primarily it is seen as a dermatological condition, but it's not
uncommon for it to develop ophthalmological implications affecting eyelids,
cornea and conjunctiva. The article describes main aspects of its
etiopathogenesis, variations in its clinical course and treatment approaches.
There is currently no universal treatment strategy for the disease due to its
varying clinical manifestation, particularly of its ophthalmological form,
differing severity of the pathological process, lack of knowledge about its
etiology and pathogenesis. Leading role in its pathological process belongs to
disturbance of regulatory mechanisms of the vascular, immune and nervous systems.
Additionally, higher levels of metalloproteinases and vascular endothelial growth
factor (VEGF) can be observed. Possible influence of a range of micro-organisms
also hasn't been excluded. Basic therapy involves both systemic and topical
drugs. The first include tetracycline antibiotics. A new direction in Rosacea
treatment that aims at structural and functional restoration of vascular
endothelium, improvement of microcirculation and recovery of rheological
properties of blood is angioprotector therapy, in particular with Calcium
Dobesilate (Doxi-Hem). Aside from systemic drugs, the ophthalmological forms of
Rosacea are treated topically with anti-inflammatory preparations,
immunosuppressants and artificial tears that are chosen depending on the
symptoms' severity. In cases with heavy corneal damage, various types of
keratoplasty can be performed. Collaboration between ophthalmology and
dermatology specialists is necessary in order to choose adequate strategy for
Rosacea treatment.
PMID- 29953093
TI - [First female medical resident trainee at Moscow University's ophthalmology
clinic - Ekaterina Dmitrievna Kastalskaya].
AB - On the basis of archival documents and literary publications presented creative
biography and professional work of the first female ophthalmologist Eye hospital
clinic of Moscow University E.D. Kastalskaya.
PMID- 29953094
TI - Feasibility Study of Language Lateralization using Thai Version of Language
Paradigm for Functional MRI in Clinical Service.
AB - Objective: To evaluate the concordance of language lateralization between
functional magnetic resonance imaging (fMRI) using Thai version of language
paradigm and Wada test or awake surgery with direct cortical brain stimulation
(DCS). Material and Method: Retrospective study of thirteen patients (3 males and
10 females with mean age of 33.9 years old) with epilepsy (7 cases) or brain
tumor (6 cases) was performed. Every patient underwent both fMRI (word
generation, verb generation, naming picture, and sentence completion tasks) and
Wada test or awake surgery with DCS (defined as the gold standard). The
lateralization index (LI) of fMRI was automatically calculated by using the LI
toolbox on SPM8. The hemispheric lateralization was also evaluated visually. The
concordance between fMRI and gold standard were analyzed. Results: The
concordance between the lateralization of fMRI by visual assessment and gold
standard was 92.3%. Concordance between the calculated LI by fMRI and gold
standard was varied along with the task and regional calculation method. The
concordance was good in all tasks (except for naming picture task) when using
calculated LI from frontal or whole brain excluded cerebellum and occipital lobe
(range 76.92 to 88.98% and 76.92 to 92.31%, respectively). Conclusion: There was
good concordance between fMRI and gold standard. Regional calculation from
frontal lobes and whole brain excluded cerebellum and occipital lobes gave the
best results. The results supported feasibility to use the fMRI with Thai
language paradigm as an alternative way to determine the language dominant
hemisphere in Thai patients. In case of language dominant hemisphere is unclear,
further invasive investigation of language mapping such as Wada test or DCS is
crucial.
PMID- 29953095
TI - [Transanal mesorectumectomy for rectal cancer - is it optimal surgery for
'difficult' patients?]
AB - AIM: To compare short-term outcomes after transanal total mesorectumectomy (Ta
TME) and laparoscopic (Lap-TME) procedure in 'difficult' patients. MATERIAL AND
METHODS: Prospective nonrandomized trial included patients with confirmed middle
/low rectum adenocarcinoma T1-4aN0-2M0 for the period November 2013 - September
2016. We identified 20 out of 55 in TA-TME and 14 out of 54 patients in Lap-TME
group as those of 'difficult' subgroup: male, BMI >=25 kg/m2, previous
chemoradiotherapy (CRT). RESULTS: Time of surgery, blood loss, conversions rate,
postoperative morbidity and length of hospital-stay were similar in both groups.
Hardware anastomoses were more frequent in TA-TME compared with LAP-TME group
(78.9% vs. 50%, p=0.086). Specimen quality was more favorable in TA-TME group:
Grade I 10% in Ta-TME group vs. 28.6% in Lap-TME group; 'positive' CRM 5% vs.
14.3%, r=0.365. Within-group analysis did not reveal any differences between
'difficult' and 'typical' patients by surgical and pathomorphological
characteristics in TA-TME group in contrast to Lap-TME group. Median of follow-up
was 24.6 (IR 10.6-40.2) and 23.8 (IR 12.1-39.9) months for TA-TME and Lap-TME
groups, respectively. Local recurrence occurred in 1 (1.8%) 'difficult' patient
after Ta-TME. Distant metastases were observed in 1 (1.8%) patient of Ta-TME and
2 (3.7%) patients of Lap-TME group. Actuarial 3-years reccurence-free survival
was 95.7% for Ta-TME and 93.9% for Lap-TME group, respectively (p=0.923).
CONCLUSION: TA-TME is advisable for 'difficult' patients. Further multicenter
randomized trials are necessary to specify the effectiveness of TA-TME in these
patients.
PMID- 29953096
TI - [Transtumoral decompression in acute left-sided colonic obstruction].
AB - AIM: To prove an effectiveness of transtumoral decompression in patients with
acute malignant left-sided colonic obstruction. MATERIAL AND METHODS: 154
patients with acute left-side colonic obstruction were enrolled. Patients were
divided into 4 groups. In groups 1-3 (n=120) patients underwent surgery at the
moment of colonic obstruction, in 34 patients obstruction was managed with
transtumoral decompression followed by radical surgery. Self-expanding metallic
stents (SEMS) were used in these patients. Radical and palliative procedures at
the moment of colonic obstruction are associated with high rate of postoperative
complications and mortality. RESULTS: Transtumoral decompression in malignant
colonic obstruction resolves the main objectives of complicated colonic cancer
management: absence of surgical trauma, endotracheal narcosis, reduced risk of
abdominal infection, possible multidisciplinary assessment of patient's status
and preparation for radical surgery.
PMID- 29953097
TI - [Experience of reconstructive laparoscopic procedures in patients with terminal
colostomy].
AB - AIM: To analyze the ways and terms of training for laparoscopy-assisted
reconstruction operations via learning curves analysis and to compare the
outcomes obtained both during training for technique and after that. MATERIAL AND
METHODS: There were 93 reconstructive laparoscopic procedures in 58 (62.36%)
patients with terminal colostomy. All patients were operated by the same surgeon.
Learning curves have been created and analyzed. RESULTS: Analysis showed that all
surgical features are achieved by the 30th intervention indicating the end of
learning period. Significantly less surgical trauma has been observed along with
development of surgery. CONCLUSION: Improved results are achieved by reduced
dissection of adhesions, the use of mechanical suture for intestinal anastomosis
and increased number of anastomoses made in intracorporeal fashion.
PMID- 29953098
TI - [X-ray-surgery of diverticular disease complicated by abscess formation].
AB - PURPOSE: Show the possibility of an alternative use of interventional radiology
techniques in complex treatment of patients with inflammatory complications of
the diverticular disease of the colon. MATERIAL AND METHODS: In 2012-2016, there
were 87 patients under our supervision with complicated diverticular disease. In
57 (65.5%) cases were diagnosed infiltrate, in 24 (27.6%) cases - abscess of
paracolon area (Ib-II type by Hinchey), in 6 (6.9%) cases (III-IV type according
Hinchey) generalized peritonitis have been identified. RESULTS: Emergency
laparotomy was performed in 13 patients. Abscesses of paracolon (Ib-II type by
Hinchey) area were diagnosed sonographically during the initial examination in 17
patients. 26 percutaneous drainage of diverticulogenous abscesses of different
localizations self-locking drainage #8Fr 'pig tail' was carried out under the
combined ultrasonic and X-ray control in this group of patients. The technical
success of percutaneous drainaging of the abscesses was achieved in all
manipulations. 13 patients had a single drainaging, and for diverticular disease
disease-free during the observation period of 1 year to 5 years. Resection of
the colon in a planned manner after percutaneous drainage of recurrent abscess of
paracolon area was performed in 4 patients. Complications related with the
technique of installing drainage were not reported, mortality in the group of
drained patients was absent. CONCLUSION: Ultrasound examination of patients with
suspected inflammatory complications of diverticular disease - a necessary and
sufficient method for initial diagnosis of the disease. Percutaneous drainage of
diverticulogenous abscesses (Hinchey Ib-II) is represented by the pragmatic
'first line' choice in patients with complicated diverticular disease, that
allows to treat the pathology steadfastly in most of the cases.
PMID- 29953099
TI - [Tracheolaryngeal resection for cicatricle stenosis].
AB - AIM: To determine the safest and the most effective surgical treatment of
patients with cicatricle stenosis of tracheolaryngeal segment via analysis of
different approaches. MATERIAL AND METHODS: For the period 1963-2015 at Petrovsky
Russian Research Center for Surgery and Sechenov First Moscow State Medical
University 1128 patients with cicatricle tracheal stenosis have been treated.
There were 683 men and 445 women. 684 (60.6%) patients were young and the most
employable (21-50 years). All patients were divided into 2 groups depending on
time of treatment: the first one included 297 patients between 1963 and 2000, the
second group - 831 patients between 2001 and 2015. In group 1 tracheolaryngeal
anastomosis was made in 10 (16.9%) out of 59 patients who underwent tracheal
resection. Previously indication for this surgery was cicatricle stenosis of
cervical trachea and larynx with upper borderline of cicatricle changes at least
2 cm from vocal folds. In group 2 these procedures were more frequent. 94 (28.5%)
out of 330 patients underwent tracheolaryngeal resection. Cranial borderline of
lesion was within 0.5 cm from the vocal folds (only if posterior laryngeal wall
at the level of cricoid cartilage was intact). Difficult patients are those who
need for double-level or redo repair and procedures with tracheostomy. RESULTS:
In the second group overall morbidity after tracheal resections followed by
anastomosis was 5.6%. These complications were more common after tracheolaryngeal
anastomosis (17%). There were no lethal outcomes after 94 tracheolaryngeal
resections. Good long-term results were observed in 89.8% of patients after
circular resection. Their quality of life was similar to that of healthy people.
Preserved cicatricle tracheal segments during tracheal repair with T-shaped
airway tube adversely affects quality of life in these patients in long-term
period.
PMID- 29953100
TI - [Intrahepatic cholangiocarcinoma followed by vascular invasion: is surgical
treatment justified?]
AB - : Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive tumors
associated with poor prognosis. Radical surgery is still the main method of
treatment in resectable cases. Certain difficulties are observed in case of
locally advanced tumors followed by inferior vena cava (IVC) and portal vein (PV)
invasion. AIM: To analyze safety of advanced liver resections combined with great
vessels repair for locally advanced large and multiple cholangiocellular
carcinoma. MATERIAL AND METHODS: Since January 2014 till April 2017 eighty ICC
patients have undergone advanced liver resection. There were 62 patients with
portal cholangiocarcinoma and 18 with ICC. 4 ICC patients required vascular
repair: IVC replacement in 2 cases (i.e. under venous bypass in 1 of them),
tangential and circular resection of portal vein bifurcation - in 2 cases.
RESULTS: Postoperative complications Clavien-Dindo IIIa developed in all cases.
There were no vascular complications. The length of hospital-stay was 14 - 35
days. There were no lethal outcomes. Annual survival was 50%, 2-year - 25%.
Adjuvant chemotherapy was used in all patients. CONCLUSION: Advanced liver
resection followed by IVC and PV repair for locally advanced ICC may be safely
performed and subsequently allows chemotherapeutic treatment.
PMID- 29953101
TI - [Fast track rehabilitation in perforated duodenal ulcer].
AB - AIM: To analyze the outcomes of fast track rehabilitation program in patients
with perforated duodenal ulcer (PDU). MATERIAL AND METHODS: For the period 2013
2016 at the Department of Surgery and Endoscopy 206 PDU patients have been
treated. Inclusion criterion for the main group (n=77) was duodenal ulcers, their
dimension up to 1 cm, laparoscopic suture of perforated ulcer, fast track
rehabilitation program implementation. The control group consisted of 129
patients who underwent open suturing of perforated ulcer followed by conventional
treatment in postoperative period. RESULTS: In the main group (n=77) laparoscopic
suturing of ulcerative defect with the use of Fast Track program was performed.
Postoperative complication i.e. sutures failure was observed in 1 (1.3%) case.
There were no lethal outcomes in the main group. Mean length of hospital-stay was
4.8 days. In 129 patients of the control group open suturing of the perforated
ulcer and conventional postoperative therapy were applied. Postoperative surgical
complications were absent in the control group; mortality rate was 2.3%. Mean
length of postoperative hospital-stay was 8.1 days. CONCLUSION: Laparoscopic
treatment of perforated ulcers facilitates application of fast track
rehabilitation program in emergency patients. Fast track rehabilitation protocol
after laparoscopic suturing of the perforated ulcer creates conditions for early
discharge and is followed by good clinical and economic effects. Recurrent peptic
ulcers are noted if antiulcer therapy is absent.
PMID- 29953102
TI - [Endoscopic retro-muscular alloplasty for primary and postoperative ventral
hernias: our initial experience].
AB - AIM: To define optimal surgical approach for middle primary and postoperative
ventral hernias. MATERIAL AND METHODS: We have presented the first results of
endoscopic retro-muscular alloplasty in 8 patients with umbilical hernia and
postoperative ventral hernia combined with rectus abdominis muscles diastase.
RESULTS: One patient had seroma above mesh implant that was evacuated under
ultrasonic control. Absent hernial protrusion and reduced diastase were noted in
all patients. There were no symptoms of recurrence, purulent-septic complications
and venous thromboembolic complications. Mortality was absent. CONCLUSION:
Further experience and analysis of long-term results are necessary to determine
the role of this technique in anterior abdominal wall hernias management.
PMID- 29953103
TI - [Preferable surgery for benign tumors of the adrenal glands].
AB - AIM: To determine optimal surgical approach in patients with adrenal tumors.
MATERIAL AND METHODS: Overall experience of treatment of patients with adrenal
tumors comprises over 300 procedures including 152 minimally invasive surgeries.
RESULTS: We have presented the advantages and relative disadvantages of various
technologies which are useful to be considered to determine the most optimal
surgery in these patients. CONCLUSION: There are no serious contradictions to use
existing surgical methods in patients with adrenal tumors. Minimally invasive
procedures along with conventional (open) interventions significantly enlarged
rational choice in surgery for adrenal neoplasms and optimized personified
approach.
PMID- 29953104
TI - [Fatal renal and neurological complications after aortic arch repair in
newborns].
AB - AIM: To evaluate effectiveness and safety of various methods of cerebral and
visceral protection during aortic arch surgery in infants. MATERIAL AND METHODS:
Retrospective analysis included 60 patients after aortic arch repair followed by
different cerebral protection technique who have been assessed for neurological
status and visceral injury in early and long-term postoperative period. Aortic
arch surgery with deep hypothermic circulatory arrest for congenital diseases was
performed in 26 patients (group 1) and antegrade unilateral selective cerebral
perfusion in 34 patients (group 2). RESULTS: Cerebral complications occurred in
28.5% of patients of the 1st group and in 7.9% of patients of the 2nd group.
CONCLUSION: Odds ratio for neurological event is significantly lower in group 2:
0.17 (0.06-0.69; p=0.02). However, there were more patients with renal
dysfunction in this group compared with group 1: 58.7% vs. 23.7% (p=0.02).
PMID- 29953105
TI - [Efficiency of the multimodal approach to analgesia in total knee arthroplasty].
AB - MATERIAL AND METHODS: The study included 160 patients with end stage knee
osteoarthritis hospitalized for primary uncomplicated TKA. There were 142 women
and 18 men (mean age 66.5 and 65.4 years respectively). In the control group
(n=100) standard protocol of perioperative pain management was applied, in the
main group (n=60) - original multimodal approach including patient's education in
order to increase his awareness and to reduce anxiety on the preoperative stage,
modified surgical technique (optimization of incision length, 'sliding window'
principle, tourniquet during the whole procedure until applying of compressive
dressing, no drains and local infiltration analgesia) and double-level
postoperative analgesia. Different factors of pain syndrome were assessed before
surgery by using of specialized tests, while the dynamics of early postoperative
pain characteristics were evaluated by individual diaries. RESULTS: Despite
decrease of pain syndrome in both groups within 3 days after TKA in the main
group these changes were significantly better (p<0.05). On the first
postoperative day 42 (70%) patients in the main group had not pain at rest, while
in the control group such cases were absent (r<0.001). There was 2-fold increase
of hours of moderate/severe pain per day in the control group compared with the
main group (r<0.001). No specific complications were identified in both groups
during follow-up. CONCLUSION: Original multimodal perioperative approach to
analgesia proved its efficiency in patients undergoing primary TKA compared with
conventional one and may be safely used in clinical practice.
PMID- 29953107
TI - [Coronary artery bypass surgery by using of operating microscope].
PMID- 29953106
TI - [Efficacy and safety of collagen biomaterial local application in complex
treatment of the diabetic foot syndrome (final results of the multicenter
randomised study)].
AB - AIM: To evaluate the efficacy and safety of collagen biomaterial application
during the 4-week follow-up of patients with diabetic foot syndrome. MATERIAL AND
METHODS: 75 patients with diabetic foot (Wagner II (69.3%) and III (30.7%)) aged
30-80 years were included in the multicenter study, among them were 50.7% with
the wound unhealed for 1.5-6 months and 49.3% over 6-48 months. Patients were
randomized into 2 groups: 1) standard therapy (n=37), 2) the additional use of
the collagen material Collost (n=38). Observation period was at least 4 weeks for
each patient. The size of ulcers, results of general and biochemical blood tests,
oximetry, microbiological testing, ultrasound of lower extremities vessels as
well as a detailed medical history, social and functional status, level of
cardiovascular comorbidity and ongoing therapy were estimated. RESULTS:
Additional use of a collagen biomaterial has led to a significant reduction
ulcers of all sizes from 13.5 to 2.1 cm2 (in the comparison group - from 12.5 to
7 cm2). The best dynamics have been registered in Wagner II (4.4-fold average
wound area regress in Collost group, from 8.8 to 2.0 cm2; average wound area
regress by 1.8 times, from 10 to 5.6 cm2 in the comparison group) than in Wagner
III group (in the main group from 55 to 21.3 cm2; in the control group from 36 to
32.4 cm2) and in ulcers existing less than 6 months. Treatment with biological
material Collost within standard therapy after 4 weeks led to increase of
complete epithelialization by 2.6% (21.1% as compared to 14.7%), while decreasing
the frequency of ineffective treatment by 4.1 (7.9% in primary and 32.4% in the
comparison group). CONCLUSION: We have proved the efficacy and safety of collagen
biomaterial topical application in a diabetic foot syndrome treatment.
PMID- 29953108
TI - [Tension pneumopericardium as a complication of transsternal transpericardial
occlusion of main bronchus stump].
PMID- 29953109
TI - [Successful endoscopic treatment of severe iatrogenic injury of common bile
duct].
PMID- 29953110
TI - [Laparoscopic removal of epidermoid cyst of the cecum].
PMID- 29953111
TI - [The case of a surgical treatment of patient with chronic leak after sleeve
gastrectomy with two-step double-tract reconstruction].
PMID- 29953112
TI - [About non-triviality of the concept 'patient's safety in surgery'].
PMID- 29953113
TI - [Attenuation of ultrasonic noise in the 10-16 kHz frequency range by earplugs].
AB - BACKGROUND: The aim of the study was to determine attenuation of earplugs for
ultrasonic noise in the frequency range of 10-16 kHz. MATERIAL AND METHODS: The
attenuation of earplugs in 1/3-octave-bands with the centre frequencies of 10
kHz, 12.5 kHz, and 16 kHz using the REAT (real-ear attenuation at threshold)
method based on the measurements of hearing threshold of subjects. The study was
carried out for 29 models of earplugs commonly used in the industry designed by
various manufacturers, including 13 models of foam earplugs, 10 models of flanged
earplugs, 5 models of headband earplugs and one model of no-roll earplugs.
RESULTS: The values of the measured attenuation of earplugs are in the range 12.9
33.2 dB for the 10 kHz frequency band, 22.8-35.2 dB for the 12.5 kHz frequency
band and 29.5-37.2 dB for the 16 kHz frequency band. The attenuation of earplugs
in the frequency range 10-16 kHz has higher values (statistically significant
changes) for foam earplugs than flanged earplugs (p = 0.0003 vs. p = 0.0006) or
headband earplugs (p = 0.0002 vs. p = 0.04). CONCLUSIONS: The tests indicated
that there is no uniform relation between the sound attenuation in the
frequencies range of 10-16 kH and the catalogue H parameter (high-frequency
attenuation value) of earplugs. Therefore, it is not possible to easily predict
the attenuation of ultrasonic noise in the frequency range of 10-16 kHz using the
sound attenuation data for the normally considered frequency range (up to 8 kHz).
Med Pr 2018;69(4):395-402.
PMID- 29953114
TI - Computational Oncology.
PMID- 29953115
TI - Immune checkpoint inhibitors and small cell lung cancer: what's new?
AB - Despite extensive research no meaningful progress in systemic treatment of small
cell lung cancer (SCLC) has been made in the past decades. Earlier attempts with
immunotherapy including interferon and vaccination approaches had limited
success. High mutational load, smoking history and potentially also the frequent
presence of paraneoplastic phenomena-indicating an activated immune system
represent a rationale for a benefit from immune checkpoint inhibitors in SCLC.
However, the likelihood of response is diminished due to poor T-cell activation
resulting from low expression of MHC class I antigens, low amounts of tumor
infiltrating lymphocytes (TILs) and low PD-L1 expression rates. Recently, early
reports from studies with checkpoint inhibitors have shown promising results with
the potential for long term disease control in a subset of SCLC patients.
However, reliable predictive biomarkers to better define the population drawing
most benefit are currently lacking. Results from ongoing phase III trials in
different treatment lines and in the maintenance setting are eagerly awaited.
PMID- 29953116
TI - Improving Emergency Department Care for Low-Risk Chest Pain.
AB - A large health care organization aimed to improve its emergency department (ED)
standard of practice for patients with possible acute coronary syndrome (ACS) by
adopting an evidence-based clinical decision tool, the HEART score, and tracking
patient outcomes and the use of hospitalization and noninvasive stress testing
for low-risk patients across 14 sites. Results showed opportunities to reduce low
value care and costs.
PMID- 29953117
TI - Correctional psychiatry in Nigeria: dynamics of mental healthcare in the most
restrictive alternative.
AB - Nigeria has poorly structured services for correctional mental health driven by a
mix of socioeconomic and legal factors. The archaic asylum systems established in
the early part of the 20th century under the Lunacy ordinance of 1916 are no
longer fit for purpose. The present strategy is to provide mental healthcare for
mentally abnormal offenders within some prisons in the country. The current
models for this are poorly staffed and underfunded. Adoption of task-shifting
approaches based on evidence-based strategies within the context of professional
innovation, government commitment and international collaboration should help to
develop and sustain the needed correctional psychiatry services.
PMID- 29953118
TI - New trends in the relationship between psychoanalysis and psychiatry.
PMID- 29953119
TI - The psychological impacts of the climate crisis: a call to action.
PMID- 29953120
TI - Mental health and life on a small island.
PMID- 29953121
TI - 52 degrees south: mental health services in the Falkland Islands.
AB - This article discusses the factors that have shaped the development of the new
mental health legislation within the Falkland Islands. The process of
implementing new legislation within this remote island community is discussed,
including the aspirations underlying the new legislation, the management of
psychiatric emergencies and the needs of the clinical team.
PMID- 29953122
TI - Community mental health in rural India: the Shifa project in Padhar Hospital,
Madhya Pradesh.
AB - People with severe mental disorders in rural India have minimal access to mental
health services. Project Shifa entails outreach to patients and families in 75
villages in rural central India. A team of local health workers led by one
psychiatrist provide assessment, medications, education and follow-up services.
PMID- 29953123
TI - Mental health information systems in resource-challenged countries: experiences
from India.
AB - Mental health information systems are increasingly being used to measure the
effectiveness of mental health interventions. Little or no data is available for
mental health service availability and service uptake in low- and middle-income
countries. Through a narrative review, this paper illustrates the importance of
routine monitoring data and suggests methods for developing, implementing and
evaluating mental health indicators in low- and middle-income countries with a
primary focus on India.
PMID- 29953124
TI - Pandora's box.
PMID- 29953125
TI - The place of psychoanalysis in French psychiatry.
AB - France is known as one of the countries where psychoanalysis still holds an
important position in various fields, and specially in psychiatry. Is it a
'culture bound syndrome' of French society, or, more seriously, a particularity
that could be useful in other contexts as well? Through consideration of the role
psychoanalysis is playing in French psychiatry, this paper will try to review
this particularity and its interactions with the organisation and values of
psychiatry in France, both in the public services and in private practice.
PMID- 29953126
TI - Measuring Brain Connectivity via Shape Analysis of fMRI Time Courses and Spectra.
AB - We present a shape matching approach for functional magnetic resonance imaging
(fMRI) time course and spectral alignment. We use ideas from differential
geometry and functional data analysis to define a functional representation for
fMRI signals. The space of fMRI functions is then equipped with a
reparameterization invariant Riemannian metric that enables elastic alignment of
both amplitude and phase of the fMRI time courses as well as their power spectral
densities. Experimental results show significant increases in pairwise node to
node correlations and coherences following alignment. We apply this method for
finding group differences in connectivity between patients with major depression
and healthy controls.
PMID- 29953127
TI - Advent of CRISPR Based Immunotherapy in Hematologic Malignancies.
PMID- 29953128
TI - The scientific standing of psychoanalysis.
AB - This paper summarises the core scientific claims of psychoanalysis and rebuts the
prejudice that it is not 'evidence-based'. I address the following questions. (A)
How does the emotional mind work, in health and disease? (B) Therefore, what does
psychoanalytic treatment aim to achieve? (C) How effective is it?
PMID- 29953129
TI - Combination of Blinatumomab and Vincristine Sulfate Liposome Injection for
Treatment of Relapsed Philadelphia Chromosome Positive B-cell Acute Lymphoblastic
Leukemia.
AB - Relapsed Philadelphia chromosome (Ph) positive Acute Lymphoblastic Leukemia (ALL)
is an aggressive lymphoid malignancy with a poor prognosis and no randomized
studies demonstrating superiority of any single salvage regimen. We present the
case of a 33-year-old woman with relapsed Ph positive precursor (pre) B-cell ALL
with rapidly rising peripheral blasts while on blinatumomab monotherapy
initially, but ultimately responded with the addition of Vincristine Sulfate
Liposome Injection (VSLI). Ponatinib was added later when it became available for
the patient, and she ultimately achieved a complete remission. Further study is
warranted to explore mechanisms of potential synergy, and the safety and efficacy
of the combination of blinatumomab and VSLI.
PMID- 29953130
TI - WHO Mental Health Gap Action Programme implementation in the Small Island
Development States: experience from the Pacific and English-speaking Caribbean
countries.
AB - Owing to the relatively small population sizes and remoteness of the Small Island
Development States (SIDS), their mental health systems face many common
difficulties. These include having few mental health specialists per country,
limited access to mental health services and low awareness. To overcome these
limitations, the World Health Organization (WHO) Mental Health Gap Action
Programme (mhGAP), which aims to decrease the treatment gap by training non
specialists, was implemented in more than 20 Pacific and English-speaking
Caribbean countries. Many lessons were learnt from the experience. Mental health
specialist support is crucial, and online training and supervision could be a
solution. mhGAP training proved to be effective to improve knowledge and
attitude, but close monitoring and supervision are needed to change clinical
practice. Awareness raising and mental health service capacity building need to
occur simultaneously. To realise sustainable development goals, countries need to
invest more in mental health, especially in human resources; mhGAP will be one
effective solution.
PMID- 29953131
TI - Psychodynamic psychotherapies for borderline personality disorders. Current
developments and challenges ahead.
AB - This article summarises the current position of evidence-based psychodynamic
psychotherapies aimed at the treatment of borderline personality disorder -
mentalisation-based treatment and transference-focused psychotherapy - noting the
main challenges they face, especially in the area of dissemination.
PMID- 29953132
TI - Psychodynamic psychotherapy training in South East Asia: a distance learning
pilot program.
PMID- 29953133
TI - Psychiatry in Shetland.
AB - The Shetland Isles are a place of breathtaking landscapes and pristine wildlife.
As harsh as the weather can be, so warm and welcoming are the people and their
proud half-Scottish, half-Scandinavian culture. Practising psychiatry in this
northernmost outpost of the UK involves significant challenges. The authors were
the only two psychiatrists based on this remote island group, which is home to 23
000 people.
PMID- 29953135
TI - Mental healthcare in Saint Lucia.
AB - St Lucia is a small island in the eastern Caribbean with a population of
approximately 200 000 people. Although St Lucia is formally ranked as a high
middle-income country, there are pockets of deprivation and relatively low living
standards. Mental health services in St Lucia have increased considerably and
advanced over recent years because of a coalition between the government of the
island and South East Asian partners. The National Mental Wellness Centre opened
several years ago and has much improved facilities. There remains a significant
shortage of community-based services, no mental health law, and a pervasive
community stigma and apprehension regarding those with mental health problems.
PMID- 29953134
TI - Nothing about us without us: the importance of local collaboration and engagement
in the global study of autism.
AB - Our current understanding of autism and other developmental disorders is
primarily based on research conducted in high-income countries, predominantly in
North America and Europe. Even within high-income countries, White participants
are overrepresented in autism research. There is now increased recognition that a
more global and diverse research representation is warranted. This paper argues
that in order for global and diverse research efforts to be effective, it is
essential to collaborate and engage with local experts and stakeholders,
including local researchers, clinicians and representatives from governmental and
non-governmental organisations. Such collaborations ensure that studies use
culturally appropriate methods and materials, and that research findings are
interpreted taking local context into account. Ultimately, these collaborations
build local capacity and foster the development of culturally and contextually
appropriate interventions that address locally perceived needs. The adage
'nothing about us without us' is vital to global autism research.
PMID- 29953136
TI - Terrorism in Pakistan: the psychosocial context and why it matters.
AB - Terrorism is often construed as a well-thought-out, extreme form of violence to
perceived injustices. The after effects of terrorism are usually reported without
understanding the underlying psychological and social determinants of the
terrorist act. Since '9/11' Pakistan has been at the epicentre of both terrorism
and the war against it. This special paper helps to explain the psychosocial
perspective of terrorism in Pakistan that leads to violent radicalisation. It
identifies the terrorist acts in the background of Pakistan's history, current
geopolitical and social scenario. The findings may also act as a guide on
addressing this core issue.
PMID- 29953137
TI - Pandora's box.
PMID- 29953138
TI - Mental health law in Saudi Arabia.
AB - During the past 30 years the Kingdom of Saudi Arabia has developed an extensive
hospital-based mental health system culminating in the passing of a mental health
law in 2014. This legislation embodies many of the international standards
promoted by the World Health Organization. However, the mechanisms for protecting
the human rights of psychiatric patients are neither sufficiently independent nor
adequately robust.
PMID- 29953139
TI - A novel mechanism for user-friendly and self-activated microdroplet generation
capable of programmable control.
AB - Unlike conventional approaches that require bulky and expensive pumping
equipment, herein, we present a simple method for self-activated microdroplet
generation and transport inside a long microchannel. The high gas-pressure in the
syringes is used to provide the built-in power of self-priming so that the
continuous phase and the dispersed phase are sequentially automated into the
generator junction to produce stabilized droplets. The volume ratio between the
aqueous and oil phases can be adjusted in a flexible way by accurately
controlling the volume of the compressed air in the two syringes, and a novel
self-activated micropumping mechanism is introduced to explain this phenomenon.
Through the flow rate test inside the microchannels under different conditions,
it is found that the flow rate of microdroplets inside the Teflon microchannel is
highly stable. As a proof of concept, this novel micropump is applied for a 3D
spiral chip for flow through PCR. It is demonstrated that this self-activated
micropump is acceptable for droplet-based continuous flow microfluidic PCR with
the thermal-cycle controlled by a single thermostatic heater, while the real-time
(RT) fluorescence signal is comparable to a commercial qPCR cycler. This self
activated, portable, and controllable droplet generator would extend the droplet
based applications to in-field analysis and facilitate the exploitation of
droplet microfluidics by non-technical users.
PMID- 29953141
TI - Insight into the mechanism of decarbonylation of methanol by ruthenium complexes;
a deuterium labelling study.
AB - In the reaction of [RuHClP3] (P = PPh3) with NaOMe in methanol, the product is
[RuH2(CO)P3]. Short reaction times show that the final product is formed through
[RuH4P3] as the major intermediate. Using NaOCD3 in CD3OD, the first formed
product is [RuH4P'3] (P' is PPh3 partially deuterated in the ortho positions of
the aromatic rings). Further reaction leads to a mixture of [RuHnD2-n(CO)P3] (n =
0, 22%; n = 1, 2 isomers each 28%; n = 2, 22%). Mechanistic aspects of both steps
of the reaction are explored and, together with previously published
calculations, they provide definitive mechanisms for both dehydrogenation and
decarbonylation in these interesting systems.
PMID- 29953140
TI - Intriguing electronic and optical properties of two-dimensional Janus transition
metal dichalcogenides.
AB - Atomically thin Janus transition metal dichalcogenides (JTMDs) with an asymmetric
structure have emerged as a new class of intriguing two-dimensional (2D)
semiconductor materials. Using state-of-the-art density functional theory (DFT)
calculations, we systematically investigate the structural, electronic, and
optical properties of JTMD monolayers and heterostructures. Our calculated
results indicate that the JTMD monolayers suffer from a bending strain but
present high thermodynamic stability. All of them are semiconductors with a band
gap range from 1.37 to 1.96 eV. They possess pronounced optical absorption in the
visible-light region and cover a large range of carrier mobilities from 28 to 606
cm2 V-1 s-1, indicating strong anisotropic characteristics. Significantly, some
monolayer JTMDs (e.g., WSSe and WSeTe) exhibit superior mobilities than
conventional TMD monolayers, such as MoS2. Moreover, the absolute band-edge
positions of the JTMD monolayers are higher than the water redox potential, and
most JTMD heterostructures have a type-II band alignment that contributes to the
separation of carriers. Our work suggests that the 2D JTMD monolayers are
promising for nanoelectronic, optoelectronic, and photocatalytic applications.
PMID- 29953142
TI - Ab initio study of medium sized boron-doped silicon clusters SinBm, n = 11-13, m
= 1-3.
AB - The ground state and energetically low structures of neutral SinBm clusters, of
medium size with n = 11-13, m = 1-3, are identified, presented and rationalized.
Structures of the nanoclusters are predicted using density functional theory
(DFT) and employing the HSE06 range-separated hybrid exchange-correlation
functional. For these systems the functional is shown to offer systematic
performance when benchmarked against high accuracy coupled-cluster CCSD(T) and
compared to well known functionals used in the literature. Discrepancies for
small size systems present in the literature are addressed and resolved. The
structural evolution patterns of the clusters are discussed and common structural
features (substructures) are identified. Cluster geometries are extensively
searched via a particle swarm optimization algorithm alongside more traditional
methodologies. In addition to the binding energies (that include zero-point
energy corrections) of the structures, the optical gaps and UV/visible absorption
spectra are reported, employing the CAM-B3LYP functional that was benchmarked
against the high level EOM-CCSD level of theory. The computed infrared spectra
are provided and discussed in length with respect to structural details. Their
effectiveness as charge transfer units is examined. Optical gaps range between
1.4-2.5 eV, and are adjustable through the boron and silicon content of the
clusters, which, along with the increased structural stability, offers promise
for applications in optoelectronics.
PMID- 29953143
TI - The nature of non-FRET photoluminescence quenching in nanoassemblies from
semiconductor quantum dots and dye molecules.
AB - Nanoassemblies formed via self-assembly based on colloidal CdSe quantum dots
(QDs) and porphyrin (H2P) dye molecules show Fluorescence Resonant Energy
Transfer (FRET) and non-FRET quenching of QD photoluminescence (PL). We present a
procedure to unravel and quantify these two relaxation pathways via dynamic and
static PL quenching experiments. Accordingly, FRET amounts at maximum to 10% of
the total quenching efficiency. Since the degree of ligand coverage is
inhomogeneously distributed across the QD ensemble PL quantum yields vary
broadly. The attachment of H2P molecules occurs preferentially to those QDs with
low ligand coverage. Along with that, nanoassembly formation deviates strongly
from Poisson statistics. Like FRET, non-FRET depends on the QD size. We assign
non-FRET quenching to the formation of specific new Cd2+ trap states following
depletion of several ligands by the spacious dye molecules. While FRET follows
quantitatively the Forster model, non-FRET appears on time scales of 1-3 ns in
new and enhanced non-radiative near-band-edge QD PL decay channels caused by a
trapping of the electrons in long-lived intra-gap states which then manifests
itself in a subsequent weak PL emission. We assign the related intra-band
emission to a recombination of deep-trap electrons and shallow-trap holes.
PMID- 29953144
TI - An amphiphilic composite material of titanosilicate@mesosilica/carbon as a
Pickering catalyst.
AB - A hierarchically core/shell-structured TS-1@silica/carbon composite material,
synthesized from titanosilicate crystals and surfactant-mediated mesosilica/resol
precursors via a self-assembly and nanocasting route, was fabricated to produce
stable oil-water-solid Pickering emulsions in alkene/H2O2 media, exhibiting
attractive interfacial activity and stability for selective epoxidation of
alkenes.
PMID- 29953145
TI - Unexpected halide anion binding modes in meso-bis-ethynyl picket
calix[4]pyrroles: effects of meso-pi (ethynyl) extension.
AB - meso-Ethynyl extended aryl-picket calix[4]pyrroles 2 and 3 are designed and
synthesized by directly anchoring arylethynyl groups at diametrically opposed
meso-positions. The critical roles of direct ethynyl linkers are manifested
through the isolation of unexpected host-anion conformers of meso-arylethynyl
calix[4]pyrroles and a significant enhancement in halide binding affinities.
PMID- 29953146
TI - From in silica to in silico: retention thermodynamics at solid-liquid interfaces.
AB - The dynamics of solvated molecules at the solid/liquid interface is essential for
a molecular-level understanding for the solution thermodynamics in reversed phase
liquid chromatography (RPLC). The heterogeneous nature of the systems and the
competing intermolecular interactions makes solute retention in RPLC a
surprisingly challenging problem which benefits greatly from modelling at
atomistic resolution. However, the quality of the underlying computational model
needs to be sufficiently accurate to provide a realistic description of the
energetics and dynamics of systems, especially for solution-phase simulations.
Here, the retention thermodynamics and the retention mechanism of a range of
benzene-derivatives in C18 stationary-phase chains in contact with water/methanol
mixtures is studied using point charge (PC) and multipole (MTP) electrostatic
models. The results demonstrate that free energy simulations with a faithful MTP
representation of the computational model provide quantitative and molecular
level insight into the thermodynamics of adsorption/desorption in chromatographic
systems while a conventional PC representation fails in doing so. This provides a
rational basis to develop more quantitative and validated models for the
optimization of separation systems.
PMID- 29953153
TI - New development in the enantioselective synthesis of spiro compounds.
AB - The enantioselective synthesis of spirocycles has long been pursued by organic
chemists. Despite their unique 3D properties and presence in several natural
products, the difficulty in their enantioselective synthesis makes them
underrepresented in pharmaceutical libraries. Since the first pioneering reports
of the enantioselective construction of spirosilanes by Tamao et al., significant
effort has been devoted towards the development of new promising asymmetric
methodologies. Remarkably, with the advent of organocatalysis, particularly over
six years, the reported methodologies for the synthesis of spirocycles have
increased exponentially. The aim of this review is to summarize the latest trends
and developments in the enantioselective synthesis of spirocompounds during these
last six years.
PMID- 29953152
TI - Toward a mechanistic understanding of Feo-mediated ferrous iron uptake.
AB - Virtually all organisms require iron and have evolved to obtain this element in
free or chelated forms. Under anaerobic or low pH conditions commonly encountered
by numerous pathogens, iron predominantly exists in the ferrous (Fe2+) form. The
ferrous iron transport (Feo) system is the only widespread mechanism dedicated
solely to bacterial ferrous iron import, and this system has been linked to
pathogenic virulence, bacterial colonization, and microbial survival. The
canonical feo operon encodes for three proteins that comprise the Feo system:
FeoA, a small cytoplasmic beta-barrel protein; FeoB, a large, polytopic membrane
protein with a soluble G-protein domain capable of hydrolyzing GTP; and FeoC, a
small, cytoplasmic protein containing a winged-helix motif. While previous
studies have revealed insight into soluble and fragmentary domains of the Feo
system, the chief membrane-bound component FeoB remains poorly studied. However,
recent advances have demonstrated that large quantities of intact FeoB can be
overexpressed, purified, and biophysically characterized, revealing glimpses into
FeoB function. Two models of full-length FeoB have been published, providing
starting points for hypothesis-driven investigations into the mechanism of FeoB
mediated ferrous iron transport. Finally, in vivo studies have begun to shed
light on how this system functions as a unique multicomponent complex. In light
of these new data, this review will summarize what is known about the Feo system,
including recent advancements in FeoB structure and function.
PMID- 29953154
TI - An anti-inflammatory molecular mechanism of action of alpha-mangostin, the major
xanthone from the pericarp of Garcinia mangostana: an in silico, in vitro and in
vivo approach.
AB - alpha-Mangostin (alphaMN) is a xanthone present in the pericarp of Garcinia
mangostana Linn. which is mentioned in Ayurveda and is a widely used functional
food supplement. However, its anti-inflammatory mechanism is not well studied.
Hence, we used in silico, in vitro and in vivo models to provide information of
the mechanism on how alphaMN could prevent inflammation. Firstly, molecular
docking was used to find out the binding energy of alphaMN with NFkappaB and COX
proteins. Secondly, LPS induced RAW 264.7 cells were used to measure the
production of cytokines, the prevention of translocation of NFkappaB and the
inhibition of COX-1 and -2 enzymes. Finally, carrageenan-induced peritonitis was
used in vivo to check cytokine release, leukocyte migration and vascular
permeability. The in silico modelling had showed that alphaMN has the lowest
binding energy with COX-2 and NFkappaB proteins. alphaMN has been found to
inhibit the production of PGE2 and nitric oxide, and iNOS protein expression. TNF
alpha and IL-6 cytokines were inhibited significantly (p < 0.05) at 8 and 14 MUg
ml-1 concentration. alphaMN at higher doses inhibits the translocation of
NFkappaB together with suppressing the COX-2 enzymes, but not COX-1. alphaMN
inhibited the total leukocyte migration, predominantly, neutrophils in vivo. The
level of TNFalpha and IL-1beta was significantly (p < 0.05) reduced in the
peritoneal fluids as measured by ELISA analysis. Taken together, these results
demonstrate that alphaMN acts well as an anti-inflammatory agent via inhibiting
the hallmark mechanisms of inflammation. It can be considered as a potential
alternative lead compound. In addition, the current results support the
traditional use of this fruit pericarp as a functional food.
PMID- 29953155
TI - Quantitative evaluation of the interface lattice quality of a strain superlattice
by strain analysis.
AB - The lattice quality of strain superlattice structures in Quantum Cascade Lasers
(QCLs) directly influences the photoelectric properties and service life of the
lasers. However, the evaluation method for lattice quality on the nanoscale is
not very well developed at present, especially for interface lattice quality
assessment. In this investigation, all atoms positioned in the multiple interface
layers can be simultaneously and accurately determined through Subset Geometric
Phase Analysis (S-GPA) combined with a Peak Finding (PF) method and an Optimal
Approximation Algorithm (OAA) with a sensitivity of about 0.04 A. Based on the
determined interface location, the strain distribution in all layers of the
superlattice structure was simultaneously measured using the improved S-GPA by
means of the optimal selection of multiple reference areas. A quantitative
evaluation of the strain/stress compensation effect was then carried out based on
the theoretical model of elastic mechanics. The proposed method was successfully
applied to evaluating the lattice quality of an In0.6Ga0.4As/In0.44Al0.56As
superlattice structure grown by Molecular Beam Epitaxy (MBE). The obtained
results show that the interface lattices are almost perfect with a uniform
thickness of layers, without any defects and stress concentration. Each
In0.44Al0.56As layer and adjacent In0.6Ga0.4As layers provided effective
strain/stress compensation for each other, reducing the possibility of forming
dislocations. In one period, the active region has been properly strain-balanced
to give a nearly net zero strain. The proposed method can not only be applied in
evaluating the growth quality of the superlattice structure with a large field of
view, but also provide quantitative experimental data for further improving the
superlattice design.
PMID- 29953156
TI - Electronic structure of twisted and planar rubrene molecules: a density
functional study.
AB - X-ray absorption spectra (XAS), the density of states (DOS) and the electron
density distribution of the HOMO and LUMO for flat and twisted rubrene molecules
have been calculated using density functional theory (DFT). The simulated XAS
spectra are validated by experimental C K-edge near-edge X-ray absorption fine
structure (NEXAFS) data. We demonstrate that the NEXAFS spectra of rubrene thin
films of different thicknesses can be explained in terms of different
combinations of spectral intensity from the twisted and the flat randomly
oriented molecules. All the fine structure of the NEXAFS spectra is well
reproduced and the energetic positions of the resonances agree within a window of
+/-0.3 eV with the calculated XAS. Our calculation reveals that the peak at
lowest photon energy (alpha') of the NEXAFS spectra at the lower coverage of
rubrene molecules appears only from the twisted molecules. Other peaks in the
case of the flat molecules appear either from the backbone or the wings, whereas,
for the twisted molecules, the backbone and the wings contribute somewhat
equally. Lowering of the HOMO-LUMO gap, as well as redistribution of the electron
density of both the frontier orbitals, is found to take place in the case of the
twisted molecule. The redistribution explains the reduction in conductivity for
the twisted molecule compared to the flat one despite the lower band gap for the
former. This finding will further strengthen the progress of rubrene thin film
based devices.
PMID- 29953157
TI - Core-shell rare-earth-doped nanostructures in biomedicine.
AB - The current status of the use of core-shell rare-earth-doped nanoparticles in
biomedical applications is reviewed in detail. The different core-shell rare
earth-doped nanoparticles developed so far are described and the most relevant
examples of their application in imaging, sensing, and therapy are summarized. In
addition, the advantages and disadvantages they present are discussed. Finally, a
critical opinion of their potential application in real life biomedicine is
given.
PMID- 29953158
TI - A comparison of mutagenic PhIP and beneficial 8-C-(E-phenylethenyl)quercetin and
6-C-(E-phenylethenyl)quercetin formation under microwave and conventional
heating.
AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant
mutagen/carcinogen produced in high temperature treated protein food. Quercetin
has been shown to inhibit PhIP formation by trapping phenylacetaldehyde to form
two human beneficial adducts 6-C-(E-phenylethenyl)quercetin (6-CEPQ) and 8-C-(E
phenylethenyl)quercetin (8-CEPQ). Here we studied the formation of PhIP as well
as the phenylacetaldehyde-trapping ability of quercetin in microwave heating and
conventional heating systems. LC-MS was applied for the comparison of PhIP formed
in chemical models using microwave heating and conductive heating. Results showed
that PhIP was produced time dependently under both heating conditions. Microwave
heating produced a smaller amount of PhIP compared with conductive heating.
Moreover, quercetin showed a more potent inhibitory effect on PhIP formation in
microwave heating systems than in conductive heating models. The amount of 6-CEPQ
and 8-CEPQ produced in chemical models and onion/beef soup using microwave
heating was about 5 and 1.5 times more than using conductive heating,
respectively. Our results demonstrate that microwave heating was a much safer and
healthier thermal processing technology than conventional heating in terms of
formation of less mutagenic PhIP and production of more human beneficial
compounds 6-CEPQ and 8-CEPQ.
PMID- 29953159
TI - Effect of an external electric field on capillary filling of water in hydrophilic
silica nanochannels.
AB - Development of functional nanofluidic devices requires understanding the
fundamentals of capillary driven flow in nanochannels. In this context, we
conduct molecular dynamics simulations of water capillary imbibition in silica
nanoslits under externally applied electric (E) fields with strengths between 0
and 1 V nm-1. For increasing E-fields, we observe a systematic lowering in the
meniscus contact angle and a decrease in the corresponding water filling rates.
These results contrast markedly the classical Washburn-Bosanquet's equation which
predicts an increase in filling rates for lower water contact angles. Our study
provides evidence that the observed decrease in water filling rates can be
attributed to the interplay between two underlying mechanisms, a reduced fluidity
of interfacial water and a systematic alignment of the water molecules in the
bulk as a response to the particular strength of the applied E-field. Therefore,
during water capillary filling a constant E-field applied in the direction
parallel to the water imbibition leads to a lower than expected filling rate
caused by a viscosity increase in the bulk and an altered solid-liquid friction
on the channel walls. These coupled mechanisms governing capillarity under the
action of applied E-fields could be manipulated for controlling imbibition of
polar liquid solutions in nanofluidic devices.
PMID- 29953160
TI - Intramolecular metal-ligand electron transfer triggered by co-ligand
substitution.
AB - The possibility of directed stimulation of intramolecular electron transfer
between a metal and a redox-active ligand in a molecular coordination compound is
the key to its application in molecular catalysis and other research themes.
Although the stimulation by a substitution reaction of the co-ligands is often
postulated as key step in catalytic cycles using redox-active ligands as electron
reservoirs, there are only a few explicit examples for such reactions. Herein we
report the synthesis of the first dicationic and dinuclear CuI complexes
featuring the oxidized form of a redox-active tetrakisguanidine ligand (1,2,4,5
tetrakis(tetramethylguanidino)benzene 1) as a bridging ligand and two neutral co
ligands L (acetonitrile or pyridine), [1{Cu(Cl)L}2]2+. An intramolecular electron
transfer between the copper atom and the tetrakisguanidine ligand 1, leading to a
dinuclear CuII complex with the reduced form of the tetrakisguanidine ligand 1,
is triggered by substitution of the neutral co-ligands L.
PMID- 29953161
TI - Characterization of visible-light photo-Fenton reactions using Fe-doped ZnS (Fex
ZnS) mesoporous microspheres.
AB - A series of Fe-doped ZnS (Fex-ZnS) photocatalysts were synthesized using a one
pot hydrothermal method. The physicochemical properties of the as-prepared Fex
ZnS microspheres were characterized by different microscopic and spectroscopic
techniques. Fe doping did not obviously change the morphology and crystallinity
of ZnS, but effectively broadened the light response range into the visible-light
region. Degradation of p-nitrophenol (PNP) was used to evaluate the
photocatalytic performance of the Fex-ZnS catalysts under visible light
irradiation with the addition of H2O2 to facilitate photo-Fenton-like reactions.
The highest PNP removal rate of 83.8% after 180 min of irradiation was achieved
under the optimal conditions, including a doping ratio of 6%, a H2O2
concentration of 3 mmol L-1 and a catalyst dosage of 0.8 g L-1. The effects of
aqueous/solid mass transfer and intraparticle mass transfer limitations on the
PNP degradation reactions were analyzed, indicating that the variations of
catalyst size caused by different Fe doping ratios did not affect the
photocatalytic reactions in this study. The PNP removal mechanism of the Fex-ZnS
photocatalyst with H2O2 addition under visible light irradiation was proposed.
PMID- 29953163
TI - Density functional theory for charged fluids.
AB - An improved density functional theory (DFT) for an inhomogeneous charged system
(including electrolyte and/or polyelectrolyte) is proposed based on fundamental
measure theory, thermodynamic perturbation theory and mean-spherical
approximation. Our DFT combines the existing treatment of hard-sphere
contributions using fundamental measure theory (FMT) with a new treatment of the
electrostatic correlations for the non-bonded ions and chain connectivity that
are approximated by employing a first-order Taylor expansion, with the reference
fluid density determined using the technique from Gillespie et al. [D. Gillespie
et al., J. Phys.: Condens. Matter, 2002, 14, 12129]. We show that the first-order
Taylor expansion for the non-bonded electrostatic correlations yields numerically
comparable results to the more involved second-order expansion. Furthermore, we
find that the existing treatment of the chain connectivity correlation predicts a
spurious layer-by-layer phase at moderately large Bjerrum lengths, which is
avoided in our new treatment. These simplifications and improvements should
significantly facilitate the implementation and reduce the computational cost.
PMID- 29953162
TI - Investigation on the hygroscopicity of oxalic acid and atmospherically relevant
oxalate salts under sub- and supersaturated conditions.
AB - Oxalic acid (OxA) is an end product in the oxidation of many organic compounds,
and therefore is ubiquitous in the atmosphere and is often the most abundant
organic species in ambient aerosols. To better understand the hygroscopic
properties of OxA under sub- and supersaturated conditions in the atmosphere, we
investigated the hygroscopic growth and cloud condensation nuclei (CCN)
activation ability of pure OxA and its salts using a hygroscopic tandem
differential mobility analyzer (HTDMA) and cloud condensation nuclei counter
(CCNC), respectively. OxA particles absorb water under >45% RH, suggesting that
the initial phase state might be an amorphous solid. The measured hygroscopic
growth factor (HGF) of OxA at 90% RH was 1.47. We found that the HGF of ammonium
oxalate (NH4-Ox) was larger than that of OxA, whereas HGFs of sodium, calcium,
and magnesium oxalates (Na-Ox, Ca-Ox, and Mg-Ox) were smaller than that of OxA
particles. Potassium oxalate (K-Ox) behaved like a typical water-soluble
inorganic salt, exhibiting deliquescence and efflorescence transitions at around
85% and 50% RH, respectively. Na-Ox exhibited strong activation capabilities
among all the investigated salts, followed by NH4-Ox and K-Ox as inferred from
the activation ratios (CCN/CN) against supersaturations (SS). On the other hand,
Ca-Ox showed moderate activation ability and Mg-Ox showed poor CCN activation
ability. We also observed significantly higher kappaCCN values compared to
kappaHTDMA for pure OxA and its salts (NH4-Ox and Na-Ox), suggesting that the
condensation of OxA into the aqueous phase occurs during water uptake. These
findings improve the fundamental understanding of hygroscopic behaviors and phase
states of oxalic acid and its salts under sub- and supersaturated conditions in
the atmosphere and impacts of hygroscopicity on the direct and indirect effects
of aerosol particles.
PMID- 29953164
TI - Slow magnetic relaxation in a {CoIICo} complex containing a high magnetic
anisotropy trigonal bipyramidal CoII centre.
AB - We report a trinuclear mixed-valence {CoIICoIII2} complex, where the CoII centre
adopts a trigonal bipyramidal geometry, leading to a large, easy-plane magnetic
anisotropy and field-induced slow magnetic relaxation with a Raman-like
relaxation process.
PMID- 29953165
TI - Synthesis and hydroformylation evaluation of Frechet-type organometallic dendrons
with N,O-salicylaldimine Rh(i) complexes at the focal point.
AB - A series of organometallic dendrons containing N,O-salicylaldimine entities at
the focal point were synthesised by reacting the N,O-salicylaldimine
functionalised Frechet dendrons (G0, G1 and G2) with a [Rh(MU-Cl)(eta2:eta2
COD)]2 dimer to yield the corresponding Rh(COD) [COD = cyclooctadiene] complexes.
These Rh(COD) complexes were exposed to an atmosphere of CO to yield a new class
of rhodium carbonyl organometallic dendrons with Rh(CO)2 units at the focal
point. All the compounds were characterised using standard spectroscopic and
analytical techniques, these include nuclear magnetic resonance, infrared
spectroscopy, mass spectrometry and single-crystal X-ray diffraction for
compounds 1, 4 and 7. All of the complexes were evaluated in the hydroformylation
of 1-octene, with excellent conversion and chemoselectivity towards aldehydes.
The G0-(CO)2 catalyst precursor (7) was active in the hydroformylation of 1
octene, styrene, 7-tetradecene, methyl oleate, triolein, d-limonene and R
citronellal. The conversion and chemoselectivity towards aldehydes for 7
tetradecene, methyl oleate, triolein and d-limonene were promising. Across a
particular dendron series, an increase in chemoselectivity was observed due to
the dendritic effect. Mercury drop tests were performed for the G0-analogues and
these confirm that the hydroformylation can be attributed to a combination of
homogeneous and heterogeneous catalysis.
PMID- 29953166
TI - Efficient hydroboration of carbonyls by an iron(ii) amide catalyst.
AB - An easily prepared iron(ii) amide precatalyst enables the selective hydroboration
of carbonyls with HBpin (pinacolborane) in the absence of any additive. The
reactions proceed with low catalytic loading (1-3 mol%) under mild reaction
conditions and display wide functional group compatibility. Aldehydes are
selectively hydroborated in the presence of other reducible functional groups,
such as ketones, alkenes, nitriles, esters, amides, acids and halides.
PMID- 29953167
TI - Interventions for chronic non-hypovolaemic hypotonic hyponatraemia.
AB - BACKGROUND: Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs
frequently, can be caused by various conditions, and is associated with shorter
survival and longer hospital stays. Many treatments, such as fluid restriction or
vasopressin receptor antagonists can be used to improve the hyponatraemia, but
whether that translates into improved patient-important outcomes is less certain.
OBJECTIVES: This review aimed to 1) look at the benefits and harms of
interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared
with placebo, no treatment or head-to-head; and 2) determine if benefits and
harms vary in absolute or relative terms dependent on the specific compound
within a drug class, on the dosage used, or the underlying disorder causing the
hyponatraemia. SEARCH METHODS: We searched the Cochrane Kidney and Transplant
Register of Studies up to 1 December 2017 through contact with the Information
Specialist using search terms relevant to this review. Studies in the Register
are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference
proceedings, the International Clinical Trials Register (ICTRP) Search Portal and
ClinicalTrials.gov. We also screened the reference lists of potentially relevant
studies, contacted authors, and screened the websites of regulatory agencies.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi
RCTs that compared the effects of any intervention with placebo, no treatment,
standard care, or any other intervention in patients with chronic non
hypovolaemic hypotonic hyponatraemia. We also included subgroups with
hyponatraemia from studies with broader inclusion criteria (e.g. people with
chronic heart failure or people with cirrhosis with or without hyponatraemia),
provided we could obtain outcomes for participants with hyponatraemia from the
report or the study authors. DATA COLLECTION AND ANALYSIS: Two authors
independently extracted data and assessed risk of bias. We expressed treatment
effects as mean difference (MD) for continuous outcomes (health-related quality
of life, length of hospital stay, change from baseline in serum sodium
concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes
(death, response and rapid increase in serum sodium concentration,
hypernatraemia, polyuria, hypotension, acute kidney injury, liver function
abnormalities) together with 95% confidence intervals (CI). MAIN RESULTS: We
identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189
participants) compared a vasopressin receptor antagonist versus placebo, usual
care, no treatment, or fluid restriction. In adults with chronic, non
hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have
uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11,
95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision;
and on health-related quality of life because results are at serious risk of
performance, selective reporting and attrition bias, and suffer from indirectness
related to the validity of the Short Form Health Survey (SF-12) in the setting of
hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low
certainty evidence due to risk of performance bias and imprecision) (3 studies,
610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or
no difference to cognitive function (low certainty evidence due to indirectness
and imprecision). Vasopressin receptor antagonists probably increase the
intermediate outcome of serum sodium concentration (21 studies, 2641
participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a
half as many people having a 5 to 6 mmol/L increase in sodium concentration
compared with placebo at 4 to 180 days (moderate certainty evidence due to risk
of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18).
But they probably also increase the risk of rapid serum sodium correction - most
commonly defined as > 12 mmol/L/d (moderate certainty evidence due to
indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and
commonly cause side-effects such as thirst (13 studies, 1666 participants: OR
2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69,
95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity
remains uncertain due to large imprecision. Effects were generally consistent
across the different agents, suggesting class effect.Data for other interventions
such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids,
demeclocycline, lithium and phenytoin were largely absent. AUTHORS' CONCLUSIONS:
In people with chronic hyponatraemia, vasopressin receptor antagonists modestly
raise serum sodium concentration at the cost of a 3% increased risk of it being
rapid. To date there is very low certainty evidence for patient-important
outcomes; the effects on mortality and health-related quality of life are unclear
and do not rule out appreciable benefit or harm; there does not appear to be an
important effect on cognitive function, but hospital stay may be slightly
shorter, although available data are limited. Treatment decisions must weigh the
value of an increase in serum sodium concentration against its short-term risks
and unknown effects on patient-important outcomes. Evidence for other treatments
is largely absent.Further studies assessing standard treatments such as fluid
restriction or urea against placebo and one-another would inform practice and are
warranted. Given the limited available evidence for patient-important outcomes,
any study should include these outcomes in a standardised manner.
PMID- 29953168
TI - Preparation, Culture, and Analysis of Amniotic Fluid Samples.
AB - Amniotic fluid obtained via amniocentesis provides a source of fetal material
used in prenatal diagnosis. The fluid may be used directly for biochemical
analyses, fluorescence in situ hybridization (FISH), and isolation of DNA for
molecular studies, including chromosomal microarray analysis (CMA). The fluid is
typically cultured as a source of metaphase cells for chromosome analysis and to
provide additional material for biochemical and DNA-based testing. This unit
describes an in situ method for the preparation, culture, and harvest of amniotic
fluid samples for metaphase chromosome analysis. Cells are grown, harvested for
metaphase spreads, and analyzed on glass coverslips. The unit also describes
methods to obtain cells for additional studies (such as molecular genetic
analyses) by growing cells in flasks either following passaging of cells from a
glass coverslip culture or by directly establishing a flask culture from the
amniotic fluid specimen. When cells are grown in flasks, they must be removed
from the flask with trypsin before they can be used in studies. Lastly, this unit
describes a method for isolating DNA for CMA from uncultured amniotic fluid and
cultured cells. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29953169
TI - S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood
Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral
Infection and Alcohol Use Disorder.
AB - BACKGROUND: Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both
adversely affect the immune system resulting in alterations in immune cell
signaling and inflammatory processes. The aim of this study was to investigate
how comorbid AUD contributes to abnormalities in inflammatory mediators and
psychiatric impairments in adults with HCV. METHODS: Alcohol use, mood, and
inflammatory factors were evaluated at 3 time points (baseline, week 4, and week
12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD.
Peripheral indices of immune activation, blood-brain barrier (BBB) damage (S100
calcium-binding protein B [S100B]), liver function, and viral load were measured
using immunoassays and polymerase chain reaction assays. RESULTS: Comorbid AUD
was associated with increased symptoms of depression and anxiety, elevated levels
of liver enzymes, and altered expression of inflammatory factors. Alcohol
consumption was positively correlated with the severity of psychiatric symptoms.
Univariate analysis identified significant group differences in interleukin (IL)
8 (p = 0.006), IL-10 (p = 0.03), and S100B (p = 0.048), with increased levels in
participants with AUD, which persisted over time despite reductions in alcohol
use and no significant change in HCV viral load. Statistically significant
effects of study group or time were not found for the other immune factors
assessed. Exploratory receiver operating characteristic curve analysis evaluated
the ability of IL-8, IL-10, and S100B to differentiate between levels of alcohol
consumption and generated biomarker cutoff values used to identify low risk and
unhealthy alcohol use groups. CONCLUSIONS: These results demonstrate that HCV and
comorbid AUD are associated with greater psychiatric impairments, potentially
resulting from increased inflammation, dysregulated cytokine expression, and
compromised BBB function. Alcohol-induced BBB damage may increase the risk of
neuropathological consequences within the context of chronic HCV infection.
PMID- 29953170
TI - [In process].
PMID- 29953171
TI - Efficacy and Safety in 1% Clotrimazole Powder, Adjuvant Therapy in Patients with
Superficial Fungal Cutaneous Infection in Intertriginous Areas.
AB - Background: Superficial fungal cutaneous infection is commonly found in
intertriginous area. Objective: To assess 1% clotrimazole powder (1% CP) efficacy
for adjuvant treatment of superficial fungal cutaneous infection in
intertriginous areas. Material and Method: The study performed as an open-label,
randomized, comparative study for evaluating the effects of 1% clotrimazole cream
(1% CC) with 1% CP in patients infected with dermatophytes (DMPs) or Candida spp.
in intertriginous area, comparing to patients treated with 1% CC as control by
demonstrating complete cure rate at 4, 8, and 12 weeks as well as relapse rates
during a 24-week period including patient satisfaction. Results: Sixty-seven
patients with mean age of 54.6 years were included in this study. Of those, 61.2%
were males. Thirty-five patients were infected with DMPs and 32 with Candida spp.
The complete cure rates of experimental group were significantly higher than the
control group, as observed within four weeks (p = 0.01), especially for
dermatophyte infection (p = 0.039). Two cases had recurrent candidiasis in the
control group. In both groups, relapse up to 24 weeks were not statistically
different. Additionally, there was no difference in patients' satisfaction
towards convenience of drug application. Conclusion: Using of the 1% CP could be
suggested as an adjuvant therapy and possibly preventive agent for superficial
fungal cutaneous infection in intertriginous areas.
PMID- 29953172
TI - The Revised Guidelines of the Medical Council of India for Academic Promotions :
Need for A Rethink.
PMID- 29953173
TI - Changes in Physical Fitness and Anthropometric of Medical Cadets Over Their Study
Period in Phramongkutklao College of Medicine.
AB - Objective: To assess changes in physical fitness level and anthropometric
characteristics of medical cadets in Phramongkutklao College of Medicine (PCM).
Material and Method: A prospective study was conducted in 73 male and 20 female
medical cadets at PCM during their study through medical education between April
2008 and July 2012. Anthropometric measurement and physical fitness test were
performed at initial, preclinical year, and clinical year including body weight,
height, waist-hip circumference, body mass index (BMI), waist-hip ratio (WHR),
waist-height ratio (WHtR), % body fat, grip and leg strength, maximal oxygen
uptake (VO2 max), 2-minute push-ups, 2-minute sit-ups, and 2-kilometer run for
time. Results: Through the course of medical education, significant increase
(p<0.05) in body weight, height, waist circumference, hip circumference, BMI,
WHR, WHtR, and % body fat were detected. The increments in body weight and BMI in
males were greater than in females. When compared to initial fitness, medical
cadets in preclinical year could improve physical fitness variables with
statistical significance reported in VO2 max, numbers of push-ups, sit-ups, and 2
kilometer run. When compared to preclinical year, VO2max was significant
decreased and run time was significant increased in clinical year (p<0.05).
Conclusion: Male medical cadets tended to gain more weight over the four years
spent at PCM. Health-related physical fitness of medical cadet improved in
preclinical year and cardiorespiratory fitness declined in clinical year. To
establish motivation to have regular physical activity in medical student,
physical fitness test and anthropometric measurement should be integrated into
the medical student's curriculum.
PMID- 29953174
TI - [Assessment of the severity scores in patients included in a sepsis code in an
Emergency Departament].
AB - OBJECTIVE: The objective of the study is to determine the usefulness of the SOFA
(Sequential Organ Failure Assessment), quick SOFA (qSOFA), LODS (Logistic Organ
Dysfunction System) and EWS (Early Warning Score) scores to predict in-hospital
mortality among septic patients attended in the emergency department; to evaluate
what factors are associated with mortality; and develop a predictive model of in
hospital mortality. METHODS: Retrospective study including patients over 14 years
of age included in the sepsis code of an Emergency Department of a University
Hospital between November 2013 and September 2015. Demographic variables,
hemodynamic and analytical variables, and in-hospital mortality were collected to
obtain qSOFA, SOFA, LODS, EWS scores. Receiver operating characteristic curves
were constructed for each score. Logistic regression was used to evaluate the
probability of in-hospital mortality. RESULTS: A total of 349 patients were
analyzed, median age 72.7 (range 86), males: 54.4%. The in-hospital mortality was
21.8%. AUC obtained: LODS: 0.73 (IC 95% 0.67-0.80; p<0.001), EWS: 0.73 (IC 95%
0.65-0.81; p<0.001), SOFA: 0.72 (IC 95% 0.65- 0.78; p<0.001), qSOFA: 0.67 (IC 95%
0.58-0.76; p<0.001). After the multivariate analysis, these were the independent
factors associated with in-hospital mortality: Oxygen saturation <=92%, Glasgow
coma score <14, lactate >=2mmol/L (p<0.05). Two prognostic models were generated:
MPRO1: age, oxygen saturation <=92% and Glasgow coma score <14, AUC: 0.78 (IC 95%
0.72-0.84; p<0.001) and MPRO2 formed by the previous ones and lactate >=2mmol/L,
AUC: 0.82 (IC 95% 0.76-0.87; p<0.001). CONCLUSIONS: SOFA score and the new
developed scores could be useful in asses the risk of in-hospital mortality in
patients included in the sepsis code.
PMID- 29953175
TI - A patient with a rapidly lethal pneumonia after a visit to a touristic area in
rural Leon (Spain).
PMID- 29953176
TI - Spinal Gnathostomiasis: A Case Report with Magnetic Resonance Imaging and
Electrophysiological Findings.
AB - Background: Spinal gnathostomiasis results in serious multiorgan impairments.
Magnetic resonance imaging (MRI) and serology help in diagnosis, and assessing
the severity and extent of the disease. However, the physiology of neural pathway
could not be demonstrated. Electrodiagnosis may have a role in demonstrating the
functions of the central and peripheral neural pathways and prognostic assessment
of the disease. Material and Method: An 18-year-old man presented with radicular
pain and rapid progressive weakness of lower extremities, leading to paraplegia
in three days. A clinical evaluation and laboratory tests, including serology,
MRI, and electrodiagnosis, were performed. Results: The investigation showed L1
paraplegia with urinary retention. The serial MRI of T-spine showed longitudinal
T2 hypointense lesion along the lower thoracic spinal cord, representing track
like hemorrhage with spinal cord edema at the onset of symptoms, nodular
enhancement of T11-T12 spinal cord, and enhancing and clumping of cauda equina
nerve roots in the MRI at two months after the first MRI. The CSF and serum for
Gnathostoma antibody were positive. Intravenous corticosteroid and oral
albendazole were given. Three months after treatment, the symptoms improved in
sensation but not in motor function. The electrodiagnosis was performed. There
were very small amplitudes and no response in bilateral tibial and peroneal motor
nerve conduction studies (NCS) respectively. The bilateral sural sensory NCS were
normal. Neither tibial somato-sensory evoke potentials (SSEP) nor motor evoke
potential (MEP) was recorded. No further improvement of patient's clinical status
at eight months after onset was observed. Conclusion: Electrophysiological
findings demonstrated the function of spinal cord and peripheral nerves in the
patient with spinal gnathostomiasis. There were correlations between MRI and
electrophysiological findings that confirmed pathophysiology of the disease.
Absence of SSEP and MEP response correlated with poor neurological outcomes in
radiculomyelitis caused by Gnathostoma spp. infection.
PMID- 29953177
TI - Herbal Induced Hepatoprotection and Hepatotoxicity: A Critical Review.
AB - Traditional herbal drugs are wonderful remedies for the treatment of various
devastating disorders. Recently, there has been a change in a universal fashion
from synthetic to herbal medicine, which is like homecoming to nature. In the
present situation, the dietary changes lead to liver disorders like non-alcoholic
and alcoholic fatty liver disorders. India is one of the world's twelve leading
biodiversity centers with the presence of over45,000 diverse plant species, out
of this about 15,000-20,000 plants have good medicinal and therapeutic properties
of which only about 7,000-7,500 are being used by traditional practitioners.
Hepatic injury accounts for 3.5%-9.5% of all adverse drug reaction reports and up
to 14.7% of fatal adverse reaction. Hepatic disorders/toxicity can occur by
several mechanisms like Cytochrome P450 activation, lipid peroxidation,Induction
of nitric acid synthase, mitochondrial dysfunction, activation of pro
inflammatory mediators and Bile acid-induced liver cell death. There are a number
of drugs or therapies available for the treatment of hepatic disorders, but still
there is a need for the novel drug discovery which can target multiple disease
pathways. Traditional medicines have exhaustive ancient and scientific literature
for curing a lot of life threatening disorders with less or no side effects.
There are number of scientifically proved hepatoprotective herbal drugs like
Andrographis paniculata, Ocimum sanctum, Solanum nigrum, Silybum marianum,
Phyllanthus niruri etc. which are widely used for the treatment of liver
disorders. However, there are various herbal plantsand phytoconstituents, which
are found to be hepatotoxic like Lanata camra Linn, Symphytum officinale,
Azadirachta indica, Amantia phalloides etc. This review emphasizes on both sides
of the coin like crucial aspects of phytoconstituents with reference to their
hepatoprotective as well as hepatotoxic effects linked to use of herbal
preparations.
PMID- 29953178
TI - Parkinson's Disease: Basic knowledge.
AB - Pharmacotherapy in Parkinson's disease is complex and requires expertise in all
health-care professions. Besides idiopathic Parkinson's disease (IPD) secondary
parkinsonism, monogenetic Parkinson's disease and atypical syndromes need to be
differentiated. The prevalence in the European population is estimated to be
approximately 1 %. Lifestyle and age are closely linked to IPD. Neurodegeneration
with formation of Lewy-bodies and increased oxidative stress in the pars compacta
of the substantia nigra are closely linked to IPD. Lewy-bodies show misfolded
alpha-Synuclein. The balance of glutamate, GABA and dopamine is essential for
motor complications. Bradykinesia/akinesia, rigidity, rest tremor and postural
instability are typical symptoms along with dissymmetry, shuffling gait and
camptocormia, micrographia, aphasia, hypophonia, dysphagia, and hypomimia. Early
symptoms are akathisia/restlessness, insomnia, somnolence, hyposmia and neck
pain. With further progression of IPD, neurons of the ventral tegmental area are
affected and lead to non-motor symptoms, which hence are directly related to the
underlying disease. Gastric dysmotility, depression, urinary incontinence,
excessive sweating, hallucinations, spasticity, muscle pain and Parkinson's
disease dementia are part of IPD.
PMID- 29953179
TI - Diagnosis of Parkinson's disease.
AB - Especially in early stages, the diagnosis of Parkinson's disease is challenging.
Patients with a suspected diagnosis should always be transferred to a neurologist
with special expertise in clinical differential diagnosis of movement disorders.
The diagnosis should be confirmed by an established three-stage algorithm which
involves the screening of clinical diagnostic criteria, possible exclusion
criteria, special characteristics of atypical parkinsonian syndromes and
supportive criteria. Besides, a secondary parkinsonian syndrome should be
considered as a possible cause of the presented clinical symptoms. Instrumental
diagnostic procedures can support the process of differential diagnosis.
PMID- 29953180
TI - In Vitro Evaluation of Carbachol and Endothelin on Contractility of Colonic
Smooth Muscle in Hirschsprung's Disease.
AB - Background: The hypomotility of colon observed in Hirschsprung's disease (HD) has
been attributed tocongenital aganglionosis only. So far, it is not clear whether
the contractility of colonic smooth muscle inthis condition is altered or not.
Therefore, the present study attempted to understand the contractile statusof
colonic segments of HD patients by examining carbachol and endothelin (ET-1)
evoked colonic smoothmuscle contractions in vitro . Methods: Contractile
responses were recorded from strips of colonic segments obtained from HD
patients,using organ bath preparations. Cholinergic agonist carbachol and ET-1
along with their antagonists wereused to evoke contractile responses. Thereafter,
the samples were histopathologically confirmed for HD. Results: Colonic strips of
HD did not show any spontaneous contractions but responded to carbachol andET-1
to a lesser extent. In HD, response of carbachol was blocked by atropine and
hexamethonium bynearly 73% and 50% respectively. ET-1 induced contractile
responses were blocked by ET-A and ET-Bantagonist up to 40%, signifying the
possible role of ET-A and ET-B receptors in HD colon contractility. Conclusion:
As evidenced by lack of spontaneous contractions and impaired carbachol and ET-1
inducedcontractile responses, it is concluded that, in addition to aganglionosis,
decreased contractility of colonicsmooth muscle may contribute to hypomotility
observed in patients with HD.
PMID- 29953181
TI - Pharmacotherapy in Parkinson's disease.
AB - Pharmacotherapy in Parkinson's disease is complex, with dopaminergic stimulation
as its backbone. During the past decade only a few new drugs have been
registered. However, progress has been made in clinical experience. Recent
studies suggest better and longer efficacy of MAO-B inhibitors. Therapy of
advanced stages of Parkinson's disease remains a challenge as the therapeutic
window narrows and motor complications prevail.
PMID- 29953182
TI - Psychotic symptoms in Parkinson's disease.
AB - We present a patient suffering from Parkinson's disease with hallucinations. A
comprehensive Medication Management can outline ways to solve drug related
problems. Hallucinations in an advanced stage of the disease are often related to
the medication. Finding the balance between controlling symptoms and provoking
psychotic adverse drug reactions is a typical clinical challenge in the treatment
of Parkinson's disease.
PMID- 29953184
TI - [In process].
PMID- 29953183
TI - Sepsis: Updated definitions and optimized management.
AB - Sepsis is newly defined as a life-threatening organ dysfunction caused by a
dysregulated host response to infection. Organ dysfunction will be determined by
an increase in the Sepsis-related Organ Failure Assessment (SOFA) score. The
updated definition should facilitate earlier recognition and more timely
management of patients with sepsis. Sepsis should be treated as quickly and
efficiently as possible as soon as it has been identified. This implies rapid
administration of antibiotics and fluids.
PMID- 29953185
TI - [In process].
PMID- 29953186
TI - [In process].
PMID- 29953187
TI - [In process].
PMID- 29953188
TI - [In process].
PMID- 29953189
TI - [In process].
PMID- 29953190
TI - [In process].
PMID- 29953192
TI - Obesity in Medical Students and its Correlation with Sleep Patterns and Sleep
Duration.
AB - The setback of sleep deficiency and sleep related disorders is colossal among the
general population. Sleep deficiency and irregularity in sleep patterns have also
been a common occurrence among doctors, as well as medical students for many
years now. The study is of great significance in the medical fraternity, as
future doctors are highly susceptible to irregular sleep patterns and duration.
Obesity is well-known disorderof the 21st century which is constantly on the
rise, carrying with it the vast Variety of health related factors. The study
included 200 medical students from the age groups18 to 24 years of which 98 were
males and 102 were females. The students were examined thoroughly, so as to
exclude those suffering from major diseases, psychological problems and those on
medication. Obesity was determined by calculating the body mass index (BMI)
according to the American journal of clinical nutrition. The grading of obesity
into various grades between 18.5 to 24.9 kg/m2, was done accordingto the world
health organization (WHO). Sleep patterns and duration were determined and
assessed by using a standardized and validatedquestionnaire: the Pittsburgh sleep
quality index (PSQI). After appropriate statistical analysis it was observed that
48 (24%) students belonged to the overweight category with BMI ranging from 30.0
to 39.9. Maximum number of students 68 (34%) had sleep duration between 5 to 6
hours daily with a mean of 6.16 and a standard deviation (SD) of 0.93. Irregular
sleep patterns were observed in a near to majority of the students with a mean of
6.82 and a standard deviation (SD) of 2.42. There was significant negative
correlation observed between BMI and sleep duration with a p value of 0.13,
highly significant positive correlation was observed between BMI and sleep
patterns (PSQI) with a p value of 0.007. Higher BMI was observed in thatcategory
of students having higher irregularity in sleep patterns and lower sleep
duration.
PMID- 29953191
TI - Aspirin Resistance in Different Doses by Bleeding Time and Urinary 11-dehydro
thromboxane B2.
AB - The aim of the present study was the evaluation bleeding time (BT) in comparison
to Urinary 11-dehydro thromboxane B2 (TXB2) regarding different ASA frequent
dosages used in Borujerd city. This is a double blind randomized clinical trial
on 370 subjects aged 35 years and older, referred to clinical offices in
Borujerd. All ischemic heart disease's patients were randomly assigned to 4 ASA
dose groups (80 mg, 81 mg, 100 mg and 325 mg) and one group-matched control group
without any IHD. BT was measured by Ivy method; TXB2 was measured in a urine
sample, both at least 5 days after ASA consumption. Probale AR was indicated if
TXB2 was normal or higher than normal higher limit values, or BT was normal or
lower thannormal higher values. (IRCT201202026958N3) Probale AR was present in
37.6% and 64% resistance by BT and TXB2, respectively. All 4 treated groups had
higher TXB2 levels than the control group/normal values (p>0.05). Also, urinary
TXB2 level correlated positively with BT. Given the simplicity and low costs of
its performance it might be of some potential use in developing countries.
However, due to IVY method limitationsit cannot be perceived as a tool to assess
such specific aspects of platlat function or aspirin resistance.
PMID- 29953193
TI - Autonomic Function Tests in Prehypertensive Young Adult Males of Uttarakhand
Region.
AB - Pre-hypertensives are at increased risk for rise in blood pressure and cardio
vascular morbidities. Autonomic dysfunction is both a cause and effect of high
blood pressure. Considering its serious prognosis the current study was
undertaken with an aim to assess autonomic functions in pre-hypertensive young
adult males. Male volunteers of 20-40 years were divided into normotensives
(n=44) and clinically healthy pre-hypertensives(n=44). They were subjected to
anthropometric measurements, Heart Rate variability (HRV) analysis along with
Standard Isometric Handgrip Test (HGT) and Sinus arrhythmia test. Analysis showed
a significant increase in sympathetic activity among prehypertensives
characterized bylower rise in DBP (mmHg) in response to HGT: [11.27+/-3.76 mmHg
vs 23.95+/-6.29 mmHg, (p<0.05)]. Parasympathetic activity was significantly
decreased among prehypertensives (HFnu: 30.02+/-14.43 vs 41.62+/-14.91, p<0.05);
E/I ratio: 1.20+/-0.10 vs 1.32+/-0.10, p<0.05). Sympathovagal balance showed
prominent sympathetic activity (2.85+/-1.78 vs 1.75+/-0.98; (p<0.01) among
prehypertensives. Salt intake amongprehypertensives was significantly higher than
normotensives (21.2+/-1.2 gm/day vs 9.0+/-0.5 gm/day: P<0.001).Conclusion:
Autonomic dysfunction is evident in prehypertensives with an enhanced sympathetic
activity, decreased parasympathetic activity and an altered sympathovagal balance
in prehypertensives, salt intake was found on a higher side. Thus lifestyle
changes in the form of balanced diet and moderate exercise may be advised to
attenuate the risk progression of prehypertension to hypertension.
PMID- 29953194
TI - Waist Circumference Rather than Body Mass Index is Better Indicator of Insulin
Resistance in Type 2 Diabetes Mellitus in North Indian Population.
AB - Obesity and insulin resistance (IR) are associated with type 2 diabetes mellitus
(DM). Obesity can be quantified by body mass index (BMI) and waist circumference
(WC). Similarly, IR is commonly quantified by fasting-plasma-insulin (FPI) and
Homeostatic model assessment (HOMA-IR). We aimed our study to find correlation
between obesity-parameters and IR especially in the Indian population where
despite lower BMI there is more prevalence of type 2 DM. In 34 uncomplicated
patients of type 2 DM weight and WC were measured and BMI was calculated. HOMA-IR
and FPI level were estimated to assess IR. Significant correlation was found
between HOMA-IR and WC (r = +0.368, P = 0.0324) but it was non-significant
between HOMAIR and BMI. Correlations were also not significant between FPI and WC
or BMI. In conclusion, HOMA-IR and WC are better measures of IR and obesity as
compared to FPI and BMI, respectively in type 2 DM.
PMID- 29953195
TI - Gender Preference for Auditory Versus Visual Routes for Memorization.
AB - Objective: Memory is formed on the basis of sensory stimuli perceived. Vision and
Auditory sense are the most common modes to form visual and auditory memory. This
study was planned to find the preferred sense route for the formation of memory,
between the two genders. Method: In the present cross sectional experimental
study, 40 male and 40 female subjects between 18-20 years of age were tested for
visual & auditory memory. Results: Results: The results suggested statistically
significant higher scores of 'Memory Test' in women in comparisonto men (F479
3.312, p=<0.001). The mean score for memory subtests was best for black & white
picturesfollowed by colored pictures, visual words, visual digits, auditory
digits and auditory words in that order inmen, whereas in women, mean score was
best for colored pictures followed by black & white pictures,auditory words,
auditory digits, visual words and visual digits. Conclusion: It may be concluded
that in men visual sense and in women auditory sense are more effectualfor the
formation of memory.
PMID- 29953196
TI - The Henderson-Hasselbalch Equation : A Three Dimensional Teaching Model.
AB - The Henderson-Hasselbalch equation can be considered as the backbone of acid base
physiology. This is conventionally represented using two dimensional plots.
Although two dimensional plots are simple to use, the equation in reality
represents a surface in three dimensional space. Any combination of PaCO2, [HCO3
] and blood pH values representing acid base disorders is restricted to this
surface. Two models depicting the three dimensional surface generated by the
Henderson-Hasselbalch equation were constructed from easily available materials.
The first model was constructed using coloured beads, thin metal rods and
plywood. This model depicted the Henderson-Hasselbalch surface as a collection of
discreetpoints. The second model depicted the Henderson-Hasselbalch equation as a
continuous surface using polystyrene sheets and white cement. The models were
presented to undergraduate and post-graduate medical students along with other
conventional two dimensional nomograms.Three dimensional models of the Henderson
Hasselbalch equation can serve as supplementary teaching material to ensure a
deeper understanding of acid base physiology.
PMID- 29953197
TI - An Interventional Study of Physical Activity on HbA1C and VO2max in Type 2
Diabetes Mellitus.
AB - Low cardio-respiratory fitness is prevalent in type 2 diabetics. The objectives
of the present study was to assess the effect of an exercise on VO2max and HbA1c
in type 2 diabetic patient. The baseline VO2max and HbA1c of 30 diabetics were
estimated. VO2max was estimated using the Bruce protocol. HbA1c was measured by
ion-exchange chromatography with Bio-Rad D10. After an exercise regimen for a
period of 6 months, theyreturned to check their VO2max and HbA1c. The baseline
VO2max was 32.67+/-11.99 ml/kg/min (low for given age) and HbA1C% values were
high (7.58+/-1.66). After walking it was found that VO2max increased and HbA1c
decreased significantly. Exercise improves cardiorespiratory fitness and lower
HbA1c. So, a suitable exercise should be incorporated along with diet and drug
prescription.
PMID- 29953198
TI - Indomethacin Exacerbates Oleic Acid-Induced Acute Respiratory Distress Syndrome
in Adult Rats.
AB - Acute respiratory distress syndrome (ARDS) is an acute fulminant condition
associated with acute lung injury and inflammation leading to hypoxemia,
pulmonary edema and respiratory failure. Even though prostaglandins are
inflammatory mediators, the role of prostaglandins in ARDS is still not clear.
Therefore, we examined the involvement of prostaglandin in experimentally induced
ARDS by using prostaglandin synthesis inhibitor, indomethacin. Experiments were
conducted on anesthetized adult rats (total n=15). Cannulation of trachea,
jugular vein and carotid artery was done in these rats. Recording of respiratory
excursions (for respiratory frequency; RF), ECG (for heart rate; HR) and blood
pressure, before and afterlethal dose of oleic acid (75 MUL i.v.) was done for
120 min or till death of the animals. Arterial blood sample was collected 15 min
after oleic acid injection to determine PaO2/FiO2 ratio. Lungs were excised at
the end of experiment for estimation of pulmonary water content. Administration
of oleic acid produced progressive increase in the RF up to 45 min followed by
decrease. Subsequently, the respiration stopped and all theanimals died by 75 min
(mean survival time = 64+/-8.2 min). HR and mean arterial pressure (MAP)
exhibited an immediate decrease followed by an increase up to 45 min. Thereafter,
the HR and MAP progressively decreased. PaO2/FiO2 ratio in this group was 182+/
2.6 mm Hg and pulmonary water content was significantly greater than saline
control group. However in indomethacin pretreated rats, injection of oleic acid
producedinstantaneous decrease in RF and all the animals died within 10 min (mean
survival time = 6.6+/-1.07 min). HR and MAP followed the same pattern as seen
with RF. Pulmonary water content in indomethacin pretreated animals was also
significantly greater than control group. These observations indicate that
indomethacin exacerbates the OA-induced ARDS. Thus, prostaglandins play an
important role in the pathophysiology ofOA-induced ARDS.
PMID- 29953199
TI - DARK Classics in Chemical Neuroscience: Phencyclidine (PCP).
AB - Phencyclidine (PCP, "angel dust", an arylcyclohexylamine) was the first non
natural, man-made illicit drug of abuse, and was coined 'the most dangerous drug
in America" in the late 1970s (amidst sensational horror stories of the drug's
effects); however, few other illicit drugs have had such a significant and broad
impact on society-both good and bad. Originally developed as a new class of
anesthetic, PCP-derived psychosis gave way to the PCP hypothesis of schizophrenia
(later coined the NMDA receptor hypofunction hypothesis or the glutamate
hypothesis of schizophrenia), which continues to drive therapeutic discovery for
schizophrenia today. PCP also led to the discovery of ketamine (and a new
paradigm for the treatment of major depression), as well as other illicit,
designer drugs, such as methoxetamine (MXE) and a new wave of Internet commerce
for illicit drugs (sold as research chemicals, or RCs). Furthermore, PCP is a
significant contaminant/additive of many illegal drugs sold today, due to its
ease of preparation by clandestine chemists. Here, we will review the history,
importance, synthesis (both legal and clandestine), pharmacology, drug
metabolism, and folklore of PCP, a true DARK classic in chemical neuroscience.
PMID- 29953200
TI - Oligomer Diversity during the Aggregation of the Repeat Region of Tau.
AB - The molecular mechanism of protein aggregation is of both fundamental and
clinical importance as amyloid aggregates are linked to a number of
neurodegenerative disorders. Such protein aggregates include macroscopic
insoluble fibrils as well as small soluble oligomeric species. Time-dependent
resolution of these species is prerequisite for a detailed quantitative
understanding of protein aggregation; this remains challenging due to the lack of
methods for detecting and characterizing transient and heterogeneous protein
oligomers. Here we have used single molecule fluorescence techniques combined
with mechanistic modeling to study the heparin-induced aggregation of the repeat
region of tau, which forms the core region of neurofibrillary tangles found in
Alzheimer's disease. We distinguish several subpopulations of oligomers with
different stability and follow their evolution during aggregation reactions as a
function of temperature and concentration. Employment of techniques from chemical
kinetics reveals that the two largest populations are structurally distinct from
fibrils and are both kinetically and thermodynamically unstable. The first
population is in rapid exchange with monomers and held together by electrostatic
interactions; the second is kinetically more stable, dominates at later times,
and is probably off-pathway to fibril formation. These more stable oligomers may
contribute to other oligomer induced effects in the cellular environment, for
example, by overloading protein quality control systems. We also show that the
shortest growing filaments remain suspended in aqueous buffer and thus comprise a
third, smaller population of transient oligomers with cross-beta structure.
Overall our data show that a diverse population of oligomers of different
structures and half-lives are formed during the aggregation reaction with the
great majority of oligomers formed not going on to form fibrils.
PMID- 29953201
TI - Multistep Inhibition of alpha-Synuclein Aggregation and Toxicity in Vitro and in
Vivo by Trodusquemine.
AB - The aggregation of alpha-synuclein, an intrinsically disordered protein that is
highly abundant in neurons, is closely associated with the onset and progression
of Parkinson's disease. We have shown previously that the aminosterol squalamine
can inhibit the lipid induced initiation process in the aggregation of alpha
synuclein, and we report here that the related compound trodusquemine is capable
of inhibiting not only this process but also the fibril-dependent secondary
pathways in the aggregation reaction. We further demonstrate that trodusquemine
can effectively suppress the toxicity of alpha-synuclein oligomers in neuronal
cells, and that its administration, even after the initial growth phase, leads to
a dramatic reduction in the number of alpha-synuclein inclusions in a
Caenorhabditis elegans model of Parkinson's disease, eliminates the related
muscle paralysis, and increases lifespan. On the basis of these findings, we show
that trodusquemine is able to inhibit multiple events in the aggregation process
of alpha-synuclein and hence to provide important information about the link
between such events and neurodegeneration, as it is initiated and progresses.
Particularly in the light of the previously reported ability of trodusquemine to
cross the blood-brain barrier and to promote tissue regeneration, the present
results suggest that this compound has the potential to be an important
therapeutic candidate for Parkinson's disease and related disorders.
PMID- 29953202
TI - Transparent Glass with the Growth of Pyramid-Type MoS2 for Highly Efficient Water
Disinfection under Visible-Light Irradiation.
AB - Water disinfection is of great importance for human health and daily life.
Photocatalysts with high efficiency, environmental protection, and narrow
bandgaps are critical for practical water treatment. Here, a general approach is
reported for the direct growth of pyramid-type MoS2 (pyramid MoS2) on transparent
glass by chemical vapor deposition (CVD). The pyramid MoS2 exhibits a smaller
bandgap and higher bactericidal activity than most TiO2-based photocatalysts. The
adjustable-bandgap nature of two-dimensional (2-D) MoS2 can harvest a wide
spectrum of sunlight and provide more active sites with which to generate
reactive oxygen species (ROS) for bacterial death in water. Furthermore, silver
(Ag) with several nanometers thicknesses is thermally evaporated on the pyramid
MoS2, which can greatly facilitate electron-hole pair separation to generate more
ROS and has a certain bactericidal effect. With our established approach, under
simulated visible light, more than 99.99% of Escherichia coli can be successfully
deactivated in 40 min, with an effective mass per unit of less than 0.7 mg L-1 in
a 0.9 wt % NaCl solution. Besides, for the first time, the generation of ROS is
confirmed with in situ Raman spectroscopy on pyramid MoS2@Ag glass, and the
related bactericidal mechanism is present as well.
PMID- 29953203
TI - Hydrolytically Degradable PEGylated Polyelectrolyte Nanocomplexes for Protein
Delivery.
AB - Novel oppositely charged polyphosphazene polyelectrolytes containing grafted
poly(ethylene glycol) (PEG) chains were synthesized as modular components for the
assembly of biodegradable PEGylated protein delivery vehicles. These
macromolecular counterparts, which contained either carboxylic acid or tertiary
amino groups, were then formulated at near physiological conditions into
supramolecular assemblies of nanoscale level, below 100 nm. Nanocomplexes with
electroneutral surface charge, as assessed by zeta potential measurements, were
stable in aqueous solutions, which suggests their compact polyelectrolyte complex
"core"-hydrophilic PEG "shell" structure. Investigation of PEGylated
polyphosphazene nanocomplexes as agents for noncovalent PEGylation of the
therapeutic protein l-asparaginase (L-ASP) in vitro demonstrated their ability to
dramatically reduce protein antigenicity, as measured by antibody binding using
enzyme linked immunosorbent assay (ELISA). Encapsulation in nanocomplexes did not
affect enzymatic activity of L-ASP, but improved its thermal stability and
proteolytic resistance. Gel permeation chromatography (GPC) experiments revealed
that all synthesized polyphosphazenes exhibited composition controlled hydrolytic
degradability in aqueous solutions at neutral pH and showed greater stability at
lower temperatures. Overall, novel hydrolytically degradable polyphosphazene
polyelectrolytes capable of spontaneous self-assembly into PEGylated
nanoparticulates in aqueous solutions can potentially enable a simple and
effective approach to modifying therapeutic proteins without the need for their
covalent modification.
PMID- 29953204
TI - Biosensor-Based Active Ingredients Recognition System for Screening STAT3 Ligands
from Medical Herbs.
AB - A surface plasmon resonance (SPR) biosensor-based active ingredients recognition
system (SPR-AIRS) was developed, validated, and applied to screen signal
transducer and activator of transcription 3 (STAT3) ligands. First, features of
the screening system were investigated in four aspects: (1) specificity of the
STAT3-immobilized chip, it shows that the chip could be applied to screen STAT3
ligands from complex mixture; (2) linearity and limit of detection (LOD) of the
system, the minimum recovery cycle number was determined as 5 cycles; (3)
saturability of the chip, the results indicate that it is necessary to select a
proper concentration based on the compound's Kd value; (4) robustness of the
system, it indicates that inactive compounds in the matrix could not interfere
with active compounds in the process of screening. Next, SPR-AIRS was applied to
screen STAT3 ligands from medicinal herbs. Nine candidate compounds were fished
out. Then SPR assay and molecular docking were performed to verify the interplay
between STAT3 and candidate compounds. Apoptosis assay and luciferase report
assay were performed to investigate the drug effect of candidate compounds on
STAT3 activity. Western blot results indicated that neobaicalein and polydatin
could inhibit the phosphorylation of STAT3. As far as we know, this is the first
time that neobaicalein and polydatin are reported as effective STAT3 ligands. In
a conclusion, we have systemically demonstrated the feasibility of SPR biosensor
based screening method applying to complex drug systems, and our findings suggest
that SPR-AIRS could be a sensitive and effective solution for the discovery of
active compounds from a complex matrix.
PMID- 29953205
TI - Evolution of Nanoparticle Protein Corona across the Blood-Brain Barrier.
AB - Engineered nanoparticles offer the chance to improve drug transport and delivery
through biological barriers, exploiting the possibility to leave the blood
circulation and traverse the endothelial vascular bed, blood-brain barrier (BBB)
included, to reach their target. It is known that nanoparticles gather molecules
on their surface upon contact with biological fluids, forming the "protein
corona", which can affect their fate and therapeutic/diagnostic performance, yet
no information on the corona's evolution across the barrier has been gathered so
far. Using a cellular model of the BBB and gold nanoparticles, we show that the
composition of the corona undergoes dramatic quantitative and qualitative
molecular modifications during passage from the "blood" to the "brain" side,
while it is stable once beyond the BBB. Thus, we demonstrate that the
nanoparticle corona dynamically and drastically evolves upon crossing the BBB and
that its initial composition is not predictive of nanoparticle fate and
performance once beyond the barrier at the target organ.
PMID- 29953206
TI - Binary Transition-Metal Oxide Hollow Nanoparticles for Oxygen Evolution Reaction.
AB - Low-cost transition metal oxides are actively explored as alternative materials
to precious metal-based electrocatalysts for the challenging multistep oxygen
evolution reaction (OER). We utilized the Kirkendall effect allowing the
formation of hollow polycrystalline, highly disordered nanoparticles (NPs) to
synthesize highly active binary metal oxide OER electrocatalysts in alkali media.
Two synthetic strategies were applied to achieve compositional control in binary
transition metal oxide hollow NPs. The first strategy is capitalized on the
oxidation of transition-metal NP seeds in the presence of other transition-metal
cations. Oxidation of Fe NPs treated with Ni (+2) cations allowed the synthesis
of hollow oxide NPs with a 1-4.7 Ni-to-Fe ratio via an oxidation-induced doping
mechanism. Hollow Fe-Ni oxide NPs also reached a current density of 10 mA/cm2 at
0.30 V overpotential. The second strategy is based on the direct oxidation of
iron-cobalt alloy NPs which allows the synthesis of hollow Fe xCo100- x-oxide NPs
where x can be tuned in the range between 36 and 100. Hollow Fe36Co64-oxide NPs
also revealed the current density of 10 mA/cm2 at 0.30 V overpotential in 0.1 M
KOH.
PMID- 29953207
TI - Intracellular Delivery via Noncharged Sequence-Defined Cell-Penetrating
Oligomers.
AB - Intracellular drug delivery systems are often limited by their poor serum
stability and delivery efficiency. Cell-penetrating peptides (CPPs), particularly
those derived from basic protein subunits, have been studied extensively in this
regard and used for the delivery of a variety of cargoes in vitro. Although
promising, traditional cationic CPPs have some drawbacks that hinder their
therapeutic application such as rapid proteolytic degradation and undesired
interactions with the biological milieu. To overcome these limitations, this
article details the discovery of a new class of noncharged cell-penetrating
oligoTEAs (CPOTs) that undergo extensive and rapid cellular entry across
different cell lines with low cytotoxicity. CPOTs outperform a widely used CPP,
R9 peptide. This new class of highly efficient noncharged macromolecular
transporters are distinct from their cationic counterparts and show strong
promise for the intracellular delivery of hydrophilic small-molecule
therapeutics.
PMID- 29953208
TI - PEI-NIR Heptamethine Cyanine Nanotheranostics for Tumor Targeted Gene Delivery.
AB - Polymer-based nanotheranostics are appealing tools for cancer treatment and
diagnosis in the fast-growing field of nanomedicine. A straightforward
preparation of novel engineered PEI-based nanotheranostics incorporating NIR
fluorescence heptamethine cyanine dyes (NIRF-HC) to enable them with tumor
targeted gene delivery capabilities is reported. Branched PEI-2 kDa (b2kPEI) is
conjugated with IR-780 and IR-783 dyes by both covalent and noncovalent simple
preparative methodologies varying their stoichiometry ratio. The as-prepared set
of PEI-NIR-HC nanocarriers are assayed in vitro and in vivo to evaluate their
gene transfection efficiency, cellular uptake, cytotoxicity, internalization and
trafficking mechanisms, subcellular distribution, and tumor specific gene
delivery. The results show the validity of the approach particularly for one of
the covalent IR783-b2kPEI conjugates that exhibit an enhanced tumor uptake,
probably mediated by organic anion transporting peptides, and favorable
intracellular transport to the nucleus. The compound behaves as an efficient
nanotheranostic transfection agent in NSG mice bearing melanoma G361 xenographs
with concomitant imaging signal and gene concentration in the targeted tumor. By
this way, advanced nanotheranostics with multifunctional capabilities (gene
delivery, tumor-specific targeting, and NIR fluorescence imaging) are generated
in which the NIRF-HC dye component accounts for simultaneous targeting and
diagnostics, avoiding additional incorporation of additional tumor-specific
targeting bioligands.
PMID- 29953209
TI - Effect of Gelation on the Colloidal Deposition of Cellulose Nanocrystal Films.
AB - One of the most important aspects in controlling colloidal deposition is
manipulating the homogeneity of the deposit by avoiding the coffee-ring effect
caused by capillary flow inside the droplet during drying. After our previous
work where we achieved homogeneous deposition of cellulose nanocrystals (CNCs)
from a colloidal suspension by reinforcing Marangoni flow over the internal
capillary flow (Gencer et al. Langmuir 2017, 33 (1), 228-234), we now set out to
reduce the importance of capillary flow inside a drying droplet by inducing
gelation. In this paper, we discuss the effect of gelation on the deposition
pattern and on the self-assembly of CNCs during droplet drying. CNC films were
obtained by drop casting CNC suspensions containing NaCl and CaCl2 salts. A mixed
methodology using rheological and depolarized dynamic light scattering was
applied to understand the colloidal behavior of the CNCs. In addition, analysis
of the mixture's surface tension, viscosity, and yield stress of the suspensions
were used to gain deeper insights into the deposition process. Finally, the
understanding of the gelation behavior in the drying droplet was used to exert
control over the deposit where the coffee-ring deposit can be converted to a dome
shaped deposit.
PMID- 29953210
TI - Hypoxia-Targeting Organometallic Ru(II)-Arene Complexes with Enhanced Anticancer
Activity in Hypoxic Cancer Cells.
AB - As hypoxia is an important factor to limit chemotherapeutic efficacy in tumors,
we herein report three ruthenium(II)-arene complexes containing a hypoxia
inducible factor-1alpha inhibitor (YC-1), which endow the organometallic
complexes with potential for hypoxia targeting. In vitro tests showed the
resulting complexes had higher anticancer activities in hypoxia than in normoxia
against the tested cancer cell lines. Western blot analysis revealed that
complexes 1-3 blocked HIF-1alpha protein accumulation under hypoxic conditions.
Moreover, these complexes displayed much less cytotoxicity toward the normal
human umbilical vein endothelial cell line (HUVEC), indicating that complexes 1-3
may be selectively cytotoxic for human cancer cell lines. These findings proved
that ligation with YC-1 endowed these organometallic ruthenium(II) complexes with
potential for hypoxia targeting in addition to enhancing their anticancer
activities.
PMID- 29953211
TI - Elucidating the Growth Mechanism of Plasmonic Gold Nanostars with Tunable Optical
and Photothermal Properties.
AB - Gold nanostars (GNSs) have received considerable attention in surface-enhanced
spectroscopies, catalysis, biosensing, photothermal therapy, and photovoltaics
because of their unique optical properties arising from the anisotropic
structure. GNSs typically consisting of a central core and several protruding
tips are usually synthesized by a seed-mediated growth approach, but the growth
mechanism and optical properties have yet to be fully understood. Here, we
systematically investigate the seed-mediated growth process of GNSs to gain an
insight into the growth mechanism and evolution of their optical and photothermal
properties. By tailoring the core size, tip length and tip angle, the main
localized surface plasmon resonance (LSPR) peak wavelength can be broadly tuned
from the visible to near-infrared (NIR) region. Our observations show that the
protruding tips grow rapidly away from the central core at the initial growth
stage, leading to a red-shift of the main LSPR peak. The preferential deposition
of gold atoms onto the gold core takes place at the later growth stage, gradually
blue-shifting the main LSPR peak. GNSs exhibit a large molar extinction
coefficient ranging from 4.0 * 108 M-1 cm-1 to 4.5 * 1010 M-1 cm-1, the log value
of which correlates linearly with the main LSPR peak wavelength and accordingly
allows for facile determination of the GNS concentration in a suspension. In
addition, GNSs are excellent NIR photothermal materials with the LSPR-dependent
photothermal conversion efficiency. The maximum photothermal conversion
efficiency of GNSs occurs at a LSPR wavelength of 740 nm, blue-shifted from the
incident laser wavelength. Our present work suggests that GNSs exhibit excellent
optical and photothermal properties that can be optimized by tailoring the
dimensional parameters.
PMID- 29953212
TI - Hydroboration of Terminal Olefins with Pinacolborane Catalyzed by New Mono(2
Iminopyrrolyl) Cobalt(II) Complexes.
AB - The 5-substituted 2-aryliminopyrrolyl ligand precursors of the type 5-R-2-[ N
(2,6-diisopropylphenyl)formimino]-1 H-pyrrole (R = 2,6-Me2-C6H3 (1a), 2,4,6-iPr3
C6H2 (1b), 2,4,6-Ph3-C6H3 (1c; reported in this work), anthracen-9-yl (1d), CPh3
(1e; reported in this work)) were treated with K[N(SiMe3)2] in toluene to yield
the respective 5-R-2-[ N-(2,6-diisopropylphenyl)formimino]pyrrolyl potassium
salts 2a-e in high yields. The paramagnetic 15-electron Co(II) complexes of the
type [Co{kappa2 N,N'-5-R-NC4H2-2-C(H)?N(2,6-iPr2-C6H3)}(Py)Cl] (3a-e; Py =
pyridine) were prepared by salt metathesis of CoCl2(Py)4 with the respective
potassium salts 2a-e in moderate to good yields. When the CoCl2(THF)1.5 precursor
was combined with the in situ prepared sodium salt of ligand precursor 1b, the
trinuclear complex [Co{kappa2 N, N'-5-(2,4,6-iPr3-C6H2)-NC4H2-2-C(H)?N(2,6-iPr2
C6H3)}(MU-Cl)]2[(MU-Cl)2Co(THF)2] (4) was obtained in high yields. Complexes 3a-e
have high-spin electronic configurations both in solution and in the solid state.
X-ray diffraction studies of complexes 3a,e confirmed distorted tetrahedral
coordination geometries. Complex 4, on the other hand, is a linear trinuclear
Co(II)-Co(II)-Co(II) complex with two terminal distorted tetrahedral four
coordinate sites and a central octahedral six-coordinate site, all in the high
spin state, S = 3/2, as confirmed by the magnetization measurements and DFT
calculations. Solid-state magnetic measurements in both complexes 3a and 4 point
to paramagnetic behavior with a significant contribution of spin-orbit coupling.
Additionally, intramolecular antiferromagnetic coupling of the adjacent cobalt
atoms is observed in 4. The Co(II) family 3a-d, on activation with K(HBEt3),
catalyzed the hydroboration of several alpha-olefins with pinacolborane, in good
to high yields (50-80%). This system almost exclusively yielded the anti
Markovnikov (a-Mk) addition product, except when styrene was used, where the
selectivity in the Markovnikov (Mk) product increased with increasing steric
bulkiness of the 5-R-2-iminopyrrolyl substituent, with the a-Mk:Mk molar ratio
varying from 2.33:1 (3a, R = 2,6-Me2-C6H3) to 0.75:1 (3c, R = 2,4,6-Ph3-C6H3).
Preliminary mechanistic studies indicate that the activation by K(HBEt3) gave
rise to a Co(I) species, the catalyst system likely following an oxidative
addition pathway.
PMID- 29953213
TI - Functional Role of Solvent Entropy and Conformational Entropy of Metal Binding in
a Dynamically Driven Allosteric System.
AB - Allostery is a regulatory phenomenon whereby ligand binding to one site
influences the binding of the same or a different ligand to another site on a
macromolecule. The physical origins of allosteric regulation remain under intense
investigation. In general terms, ligand-induced structural changes, perturbations
of residue-specific dynamics, and surrounding solvent molecules all potentially
contribute to the global energetics of allostery. While the role of solvent is
generally well understood in regulatory events associated with major protein
structural rearrangements, the degree to which protein dynamics impact solvent
degrees of freedom is unclear, particularly in cases of dynamically driven
allostery. With the aid of new crystal structures, extensive calorimetric and
residue-specific dynamics studies over a range of time scales and temperatures,
we dissect for the first time the relative degree to which changes in solvent
entropy and residue-specific dynamics impact dynamically driven, allosteric
inhibition of DNA binding by Zn in the zinc efflux repressor, CzrA (chromosomal
zinc-regulated repressor). We show that non-native residue-specific dynamics in
allosterically impaired CzrA mutants are accompanied by significant perturbations
in solvent entropy that cannot be predicted from crystal structures. We conclude
that functional dynamics are not necessarily restricted to protein residues but
involve surface water molecules that may be responding to ligand (Zn)-mediated
perturbations in protein internal motions that define the conformational
ensemble, rather than major structural rearrangements.
PMID- 29953214
TI - Magic Angle Spinning NMR Study on Inversion Behavior and Vacancy Disorder in
Alumina-Rich Spinel.
AB - Solid state magic angle spinning nuclear magnetic resonance (NMR) and X-ray
diffraction (XRD) were used to investigate the inverse behavior and vacancy
disorder in alumina-rich spinel, Mg1- xAl2(1+ x/3)O4 (0 <= x <= 0.86). Simulation
and integration of NMR spectra have been developed for probing the population of
Al located in different coordinated environments. Rietveld profile refinements
were performed for powder XRD spectra by combining with NMR analysis. With
changes in the composition, inversion disorder and cationic vacancies coexisting
in tetrahedral and octahedral coordinations fluctuate in amount in the crystal
lattice. The coordination polyhedra in the crystal structure can adjust the
volume to variations of composition, anion parameter, and inverse parameter. This
opens a window to the design and functionalization of spinel materials.
PMID- 29953215
TI - Transcriptomic and Network Analyses Reveal Mechanistic-Based Biomarkers of
Endocrine Disruption in the Marine Mussel, Mytilus edulis.
AB - Transcriptomics, high-throughput assays, and adverse outcome pathways (AOP) are
promising approaches applied to toxicity monitoring in the 21st century, but
development of these methods is challenging for nonmodel organisms and emerging
contaminants. For example, Endocrine Disrupting Compounds (EDCs) may cause
reproductive impairments and feminization of male bivalves; however, the
mechanism linked to this adverse outcome is unknown. To develop mechanism-based
biomarkers that may be linked through an AOP, we exposed Mytilus edulis to 17
alpha-ethinylestradiol (5 and 50 ng/L) and 4-nonylphenol (1 and 100 MUg/L) for 32
and 39 days. When mussels were exposed to these EDCs, we found elevated female
specific transcripts and significant female-skewed sex ratios using a RT-qPCR
assay. We performed gene expression analysis on digestive gland tissue using an
M. edulis microarray and through network and targeted analyses identified the
nongenomic estrogen signaling pathway and steroidogenesis pathway as the likely
mechanisms of action for a putative AOP. We also identified several homologues to
genes within the vertebrate steroidogenesis pathway including the cholesterol
side chain cleavage complex. From this AOP, we designed the Coastal Biosensor for
Endocrine Disruption (C-BED) assay which was confirmed in the laboratory and
tested in the field.
PMID- 29953216
TI - Total Synthesis of Salimabromide: A Tetracyclic Polyketide from a Marine
Myxobacterium.
AB - Salimabromide is an antibiotic polyketide that was previously isolated from the
obligate marine myxobacterium Enhygromyxa salina, and its densely functionalized
and conformationally rigid tetracyclic framework is unprecedented in nature.
Herein we report the first chemical synthesis of the target structure by
employing a series of well-orchestrated, robust transformations, highlighted by
an acid-promoted, powerful Wagner-Meerwein rearrangement/Friedel-Crafts
cyclization sequence to forge the two adjacent quaternary carbon centers embedded
in the tetrahydronaphthalene. A high-yielding ketiminium mediated [2+2]
cycloaddition was also utilized for the simultaneous construction of the
remaining three stereocenters.
PMID- 29953217
TI - Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional
Challenges.
AB - Advances in carbohydrate chemistry have certainly made common oligosaccharides
much more accessible. However, many current methods still rely heavily upon
specialized knowledge of carbohydrate chemistry. The application of automated
technologies to chemical and life science applications such as genomics and
proteomics represents a vibrant field. These automated technologies also present
opportunities for their application to organic synthesis, including that of the
synthesis of oligosaccharides. However, application of automated methods to the
synthesis of carbohydrates is an underdeveloped area as compared to other classes
of biomolecules. The overarching goal of this review article is to present the
advances that have been made at the interface of carbohydrate chemistry and
automated technology.
PMID- 29953218
TI - Monodisperse Magnetic Silica Hexapods.
AB - A simple yet versatile solution-based process to produce colloidal silica
hexapods is developed in which various shapes of silica rods are grown on the
faces of cubes in a controlled manner. In the presence of hematite cubic
particles, water droplets nucleate on the surface of hematite by phase separation
in pentanol. By adjusting the water concentration, six droplets can form on each
face of the hematite cube. A silica precursor is then administered into the
system, which gradually diffuses into the water droplets through the oil phase.
Within the droplets, hydrolysis and condensation of the precursors take place,
leading to formation of silica rods. As a result, silica hexapods on a magnetic
hematite cubic seed are produced. Furthermore, when the emulsions are aged at 60
degrees C prior to the silica growth, the water content in the solution decreases
gradually due to evaporation and spiky sharp hexapods are produced. On the other
hand, when organosilane precursor is added, pancake-like hexapods are formed due
to the reduction of interfacial tension. These colloidal hexapods can further be
utilized as new building blocks for self-assembly to construct functional
materials or as a model system to understand collective behaviors.
PMID- 29953219
TI - Methods for 2-Deoxyglycoside Synthesis.
AB - Deoxy-sugars often play a critical role in modulating the potency of many
bioactive natural products. Accordingly, there has been sustained interest in
methods for their synthesis over the past several decades. The focus of much of
this work has been on developing new glycosylation reactions that permit the mild
and selective construction of deoxyglycosides. This Review covers classical
approaches to deoxyglycoside synthesis, as well as more recently developed
chemistry that aims to control the selectivity of the reaction through rational
design of the promoter. Where relevant, the application of this chemistry to
natural product synthesis will also be described.
PMID- 29953220
TI - Delay of Postharvest Browning in Litchi Fruit by Melatonin via the Enhancing of
Antioxidative Processes and Oxidation Repair.
AB - Melatonin acts as a crucial signaling and antioxidant molecule with multiple
physiological functions in organisms. To explore effects of exogenous melatonin
on postharvest browning and its possible mechanisms in litchi fruit, 'Ziniangxi'
litchi fruits were treated with an aqueous solution of melatonin at 0.4 mM and
then stored at 25 degrees C for 8 days. The results revealed that melatonin
strongly suppressed pericarp browning and delayed discoloration during storage.
Melatonin treatment reduced relative membrane-leakage rate and inhibited the
generation of superoxide radicals (O2-.), hydrogen peroxide (H2O2), and
malondialdehyde (MDA). Melatonin treatment markedly promoted the accumulation of
endogenous melatonin; delayed loss of total phenolics, flavonoids, and
anthocyanins; and enhanced the activities of antioxidant enzymes, including
superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), ascorbate
peroxidase (APX, EC 1.11.1.11), and glutathione reductase (GR, EC 1.6.4.2). By
contrast, the activities of browning-related enzymes including polyphenoloxidase
(PPO, EC 1.10.3.1) and peroxidase (POD, EC 1.11.1.7) were reduced. In addition,
melatonin treatment up-regulated the expression of four genes encoding enzymes
for repair of oxidized proteins, including LcMsrA1, LcMsrA2, LcMsrB1, and LcMsB2.
These findings indicate that the delay of pericarp browning and senescence by
melatonin in harvested litchi fruit could be attributed to the maintenance of
redox homeostasis by the improvement of the antioxidant capacity and modulation
of the repair of oxidatively damaged proteins.
PMID- 29953221
TI - Toxicological Assessment of Mineral Hydrocarbons in Foods: State of Present
Discussions.
AB - The evaluation of mineral oils by the Joint FAO/WHO Expert Committee on Food
Additives (JECFA) provided high acceptable daily intakes for classes largely
falling into the mass range strongly accumulated by humans. Because they are
roughly 2 orders of magnitude above the present exposure, they authorize strongly
increased exposure. An approach based on accumulation seems more adequate.
Increased organ weights might be more critical than granulomas. Aromatic
hydrocarbons with 1-2 aromatic rings should be distinguished from those with at
least 3 aromatic rings. If mineral oil saturated hydrocarbon limits were low, no
limit might be needed for the 1-2 ring aromatics. It should be considered to
phase out substantial use of mineral oils in food application.
PMID- 29953222
TI - Control of Biohazards: A High Performance Energetic Polycyclized Iodine
Containing Biocide.
AB - Biohazards and chemical hazards as well as radioactive hazards have always been a
threat to human health. The search for solutions to these problems is an ongoing
worldwide effort. In order to control biohazards by chemical methods, a
synthetically useful fused tricyclic iodine-rich compound, 2,6-diiodo-3,5-dinitro
4,9-dihydrodipyrazolo [1,5- a:5',1'- d][1,3,5]triazine (5), with good detonation
performance was synthesized, characterized, and its properties determined. This
compound which acts as an agent defeat weapon has been shown to destroy certain
microorganisms effectively by releasing iodine after undergoing decomposition or
combustion. The small iodine residues remaining will not be deleterious to human
life after 1 month.
PMID- 29953223
TI - Stacked Genetically Engineered Trait Products Produced by Conventional Breeding
Reflect the Compositional Profiles of Their Component Single Trait Products.
AB - An expanding trend for genetically engineered (GE) crops is to cultivate
varieties in which two or more single trait products have been combined using
conventional breeding to produce a stacked trait product that provides a useful
grouping of traits. Here, we report results from compositional analysis of
several GE stacked trait products from maize and soybean. The results demonstrate
that these products are each compositionally equivalent to a relevant non-GE
comparator variety, except for predictable shifts in the fatty acid profile in
the case of stacked trait products that contain a trait, MON 87705, that confers
a high-oleic-acid phenotype in soybean. In each case, the conclusion on
compositional equivalence for the stacked trait product reflects the conclusions
obtained for the single trait products. These results provide strong support for
conducting a reassessment of those regulatory guidelines that mandate explicit
characterization of stacked trait products produced through conventional
breeding.
PMID- 29953224
TI - Change of Arsenic Speciation in Shellfish after Cooking and Gastrointestinal
Digestion.
AB - Shellfish is a common part of indigenous cuisines throughout the world and one of
the major sources of human exposure to arsenic (As). We evaluated As speciation
in shellfish after cooking and gastrointestinal digestion in this study. Results
showed that washing and cooking (boiling and steaming) can reduce As exposures
from shellfish. The use of spices during cooking processes also helped to reduce
the bioaccessibility of total As. Through mass balance calculations, we verified
the transformation of methylated As compounds into inorganic As in shellfish
takes place during cooking and that As demethylation can occur during simulated
gastrointestinal digestion. In vivo demethylation of As after gastrointestinal
digestion was also demonstrated in laboratory mice. This increase in inorganic As
during digestion suggests that risks of As toxicity from shellfish consumption
are being underestimated. Further studies on the mechanisms of As speciation
transformation in food are necessary for more thorough risk assessments.
PMID- 29953225
TI - Anti-Tobacco Mosaic Virus Quassinoids from Ailanthus altissima (Mill.) Swingle.
AB - Quassinoids are bitter constituents characteristic of the family Simaroubaceae. A
total of 18 C20 quassinoids, including nine new quassinoid glycosides, named
chuglycosides A-I (1-6 and 8-10), were identified from the samara of Ailanthus
altissima (Mill.) Swingle. All of the quassinoids showed potent anti-tobacco
mosaic virus (TMV) activity. A preliminary structure-anti-TMV activity
relationship of quassinoids was discussed. The effects of three quassinoids,
including chaparrinone (12), glaucarubinone (15), and ailanthone (16), on the
accumulation of TMV coat protein (CP) were studied by western blot analysis.
Ailanthone (16) was further investigated for its influence on TMV spread in the
Nicotiana benthamiana plant.
PMID- 29953226
TI - Seasonal Transition in PM10 Exposure and Associated All-Cause Mortality Risks in
India.
AB - Lack of a consistent PM10 (particulate matter smaller than 10 MUm) database at
high spatial resolution hinders in assessing the environmental impact of PM10 in
India. Here we propose an alternate approach to estimate the PM10 database.
Aerosol extinction coefficients at the surface are calculated from midvisible
aerosol optical depth from MERRA-2 reanalysis data using characteristics vertical
profiles from CALIOP and then are converted to PM10 mass using aerosol property
information and microphysical data. The retrieved PM10 are bias-corrected and
evaluated ( R2 = 0.85) against coincident ground-based data maintained under the
Central Pollution Control Board network. PM10 exposure exceeds Indian annual air
quality standard in 72.3% districts. Transition in PM10 exposure from the monsoon
(Jun-Sep) to postmonsoon season (Oct-Nov) translates to 1-2% higher all-cause
mortality risk over the polluted Indo-Gangetic Basin (IGB). Mortality risk
increases in the central to eastern IGB and central India and reduces in Delhi
national capital region in the winter (Dec-Feb) relative to the postmonsoon
season. Mortality risk decreases by 0.5-1.8% in most parts of India in the
premonsoon season (Mar-May). Our results quantify the vulnerability in terms of
seasonal transition in all-cause mortality risks due to PM10 exposure at district
level for the first time in India.
PMID- 29953228
TI - Mineral Composition of Dry Dog Foods: Impact on Nutrition and Potential Toxicity.
AB - Detailed mineral profile of a selection of commercially available complete dry
dog foods was determined using ICP-MS (Se, Cu, Mn, Zn, and nonessential trace
elements), flame photometry (Na and K) and atomic and molecular spectrophotometry
(Ca, P, Mg, and Fe). The contribution of ingredients to the mineral composition
was correlated to the food market segment. Results showed an oversupply of
essential elements due to the energy density effect on feed intake. Additives
contributed from 40.8 to 55.1% to the total trace elements contents. With the
exception of Se, all trace elements were supplied above the nutritional
requirements of adult dogs. Legal limits of Cu, Se, and Zn were surpassed. The
content of nonessential trace elements included values in the range of nanograms
to micrograms per kg, without surpassing safe upper limits. This work brings
awareness to the need to find supplementation strategies that ensure nutritional
adequacy and avoid waste.
PMID- 29953229
TI - Ir-Catalyzed Intramolecular Transannulation/C(sp2)-H Amination of 1,2,3,4
Tetrazoles by Electrocyclization.
AB - An efficient strategy for the intramolecular denitrogenative
transannulation/C(sp2)-H amination of 1,2,3,4-tetrazoles bearing C8-substituted
arenes, heteroarenes, and alkenes is described. The process involves the
generation of the metal-nitrene intermediate from tetrazole by the combination of
[Cp*IrCl2]2 and AgSbF6. It has been shown that the reaction proceeds via an
unprecedented electrocyclization process. The method has been successfully
applied for the synthesis of a diverse array of alpha-carbolines and 7
azaindoles.
PMID- 29953227
TI - Flavonoids, a Potential New Insight of Leucaena leucocephala Foliage in Ruminant
Health.
AB - We investigated the constituents of Leucaena leucocephala foliage collected from
Guangdong province in China and isolated 17 diverse flavonoids (1-17), including
flavones (5-9, 11, and 12), flavonols (1, 10, and 16), flavanone 4, flavanonol
15, and flavonol glycosides (2, 3, 13, 14, and 17). Flavonoids quercetin (1),
quercetin-3- O-alpha-rhamnopyranoside (2), and myricetin-3- O-alpha
rhamnopyranoside (17) were the major flavonoids components in L. leucocephala
leaves, at a total concentration of about 2.5% of dry matter. pHRE-Luc inductive
activity to mimic the activation of erythropoietin (EPO) gene, anti-inflammatory,
antidiabetic, and antioxidant activities of isolated flavonoids (1-17) were
evaluated. Flavonoids 7, 10, and 13 could strongly induce the transcriptional
activity of pHRE-Luc, which indicated their potential to induce the expression of
EPO. Flavonoids 7, 10, 13, and 17 displayed strong anti-inflammatory activity,
relatively equal to the positive control dexamethasone. Flavonoids 1, 2, 3, 11,
12, 16, and 17 showed stronger antioxidant activities of DPPH radical scavenging
capacity than ascorbic acid. Flavonoids 1, 2, and 10 showed weak cellular
antioxidant activities against tert-butyl hydroperoxide (tBHP) induced ROS
formation. Flavonoid rhamnoside 2 and arabinoside 3 undergone deglycosylation to
the aglycone quercetin under anaerobic incubation with cattle rumen
microorganisms. Furthermore, the potential health benefits for ruminant of
flavonoids, which was rich in L. leucocephala foliage, was also discussed.
PMID- 29953230
TI - Review of Hybrid Ion Capacitors: From Aqueous to Lithium to Sodium.
AB - In this critical Review we focus on the evolution of the hybrid ion capacitor
(HIC) from its early embodiments to its modern form, focusing on the key
outstanding scientific and technological questions that necessitate further in
depth study. It may be argued that HICs began as aqueous systems, based on a
Faradaic oxide positive electrode (e.g., Co3O4, RuO x) and an activated carbon
ion-adsorption negative electrode. In these early embodiments HICs were meant to
compete directly with electrical double layer capacitors (EDLCs), rather than
with the much higher energy secondary batteries. The HIC design then evolved to
be based on a wide voltage (~4.2 V) carbonate-based battery electrolyte, using an
insertion titanium oxide compound anode (Li4Ti5O12, Li xTi5O12) versus a Li ion
adsorption porous carbon cathode. The modern Na and Li architectures contain a
diverse range of nanostructured materials in both electrodes, including TiO2,
Li7Ti5O12, Li4Ti5O12, Na6LiTi5O12, Na2Ti3O7, graphene, hard carbon, soft carbon,
graphite, carbon nanosheets, pseudocapacitor T-Nb2O5, V2O5, MXene, conversion
compounds MoS2, VN, MnO, and Fe2O3/Fe3O4, cathodes based on Na3V2(PO4)3,
NaTi2(PO4)3, sodium super ionic conductor (NASICON), etc. The Ragone chart
characteristics of HIC devices critically depend on their anode-cathode
architectures. Combining electrodes with the flattest capacity versus voltage
characteristics, and the largest total voltage window, yields superior energy.
Unfortunately "flat voltage" materials undergo significant volume
expansion/contraction during cycling and are frequently lifetime limited. Overall
more research on HIC cathodes is needed; apart from high surface area carbon,
very few positive electrodes demonstrate the necessary 10 000 or 100 000 plus
cycle life. It remains to be determined whether its lithium ion capacitors (LICs)
or sodium ion capacitors (NICs) are superior in terms of energy-power and
cyclability. We discuss unresolved issues, including poorly understood fast
charge storage mechanisms, prelithiation and presodiation, solid electrolyte
interface (SEI) formation, and high-rate metal plating.
PMID- 29953231
TI - Calculations of Electronic Excitation Energies and Excess Electric Dipole Moments
of Solvated p-Nitroaniline with the EOM-CCSD-PCM Method.
AB - We present computational evidence utilizing vertical electronic excitation
energies and the corresponding excess dipole moments of solvated p-nitroaniline (
pNA). The properties of interest are calculated by employing the equation of
motion coupled cluster together with single and double excitations (EOM-CCSD).
Solvent effects are included through the polarizable continuum model (PCM) with
the state-specific (SS) formalism and the perturbation theory energy and density
(PTED) approach. We examine the ground state equilibrium geometry of pNA in
different environments to yield the symmetry of the stable conformer of solvated
pNA is C s but is also C2 v. By employing the calculated vertical excitation
energies overestimate experiment, our calculations confirm the consistency of the
calculated excess dipole moments with comparable documented results. Lastly,
specific to this study, dissimilar environmental models, such as the linear
response (LR), and variants of the corrected linear response (cLR and cLR0)
formalisms in the context of the EOM-CCSD-PCM-PTED, are assessed against those
from the SS formalism.
PMID- 29953232
TI - Correction to "Density Functional Calculations of Native Defects in CH3NH3PbI3:
Effects of Spin-Orbit Coupling and Self-Interaction Error".
PMID- 29953233
TI - Simulations of 1-Butyl-3-methylimidazolium Tetrafluoroborate + Acetonitrile
Mixtures: Force-Field Validation and Frictional Characteristics.
AB - To temper their prohibitively high viscosities, ionic liquids are commonly mixed
with polar cosolvents to retain favorable physical properties and make them
suitable for industrial applications. Molecular dynamics simulations of 1-butyl-3
methylimidazolium tetrafluoroborate ([Im41][BF4]) mixed with acetonitrile (CH3CN)
are conducted primarily to test the accuracy of a composite force field (FF) and
also to provide some insights into the solvation and frictional characteristics
of this mixture. The FF combines the united-atom model for imidazolium ionic
liquids of Zhong et al. [ J. Phys. Chem. B 2011, 115, 10027] with the
acetonitrile model of Nikitin and Lyubartsev [ J. Comput. Chem. 2007, 28, 2020].
Comparison of simulated properties such as mixture densities, viscosities,
electrical conductivities, and component diffusion coefficients to experimental
data at 298 K shows that this combined FF provides reasonable accuracy for both
static and dynamic properties. Component rotational dynamics, as well as those of
a dilute benzene solute, probed via new 2H NMR T1 measurements, are also
reasonably reproduced. Simulated coordination numbers reveal virtually random
mixing between the [Im41][BF4] and CH3CN components in this system. Comparison of
translational diffusion coefficients and rotation times to simple hydrodynamic
predictions indicates that the friction on most motions becomes increasingly
decoupled from solution viscosity as the [Im41][BF4] concentration increases.
PMID- 29953234
TI - Access to Anti or Syn 2-Amino-1,3-diol Scaffolds from a Common Decarboxylative
Aldol Adduct.
AB - A straightforward synthetic pathway allowing the access to anti or syn 2-amino
1,3-diol scaffolds is presented. The strategy relies on a diastereoselective
organocatalyzed decarboxylative aldol reaction of a N-Boc-hemimalonate that is
easily formed from commercial N-Boc-diethyl malonate. Although this method has
been optimized previously with the N-Bz-hemimalonate analogue, this key step was
reinvestigated with the N-Boc derivative to improve the required reaction time,
the yield, and the diastereoselectivity. The new conditions enhance this
transformation, and quantitative yields and anti/syn ratios up to 96:4 can be
obtained. The anti aldol product was easily isolated in pure form and then taken
forward as the key precursor in the preparation of both a set of ten N-/O
alkylated anti 2-amino-1,3-diol derivatives and the syn congeners.
PMID- 29953235
TI - The Benefit and Challenges of Zero-Dimensional Perovskites.
AB - To break free of the limitations imposed by three-dimensional (3D) perovskites,
such as their lackluster stability, researchers have opened new frontiers into
lower-dimensional perovskite derivatives. Thanks to advances in solvent-based
synthesis methods, zero-dimensional (0D) inorganic perovskites, mainly Cs4PbBr6,
have recently reemerged in various forms (from single crystals to nanocrystals)
as materials with properties that bridge organic molecules and inorganic
semiconductors. These properties include intrinsic Pb2+ ion emission, large
exciton binding energy, and small polaron formation upon photoexcitation, in
addition to anomalous green photoluminescence with improved stability and high
quantum yield. Moreover, the demonstration of Cs4PbBr6-based light-emitting diode
(LED) devices highlights the accelerating efforts toward their applications and
motivates further investigations of these emerging materials. This Perspective
summarizes the progress in the field of Cs4PbBr6 perovskites, focusing on their
molecular-electronic properties and hotly debated green photoluminescence. We
conclude by presenting the implications of the unique findings and suggesting
opportunities for the future development and applications of these 0D
perovskites.
PMID- 29953236
TI - Structure and Ion Dynamics in Imidazolium-Based Protic Organic Ionic Plastic
Crystals.
AB - A fundamental understanding of the structure and dynamics of organic ionic
plastic crystal (OIPC) materials allows for a more rational design of molecular
chemistry toward improved mechanical and electrochemical performances. This
Letter investigates the solid-state structure and ion dynamics of two imidazolium
based protic organic ionic plastic crystals as well as the ion-transport
properties in both compounds. A combination of DSC, conductivity, NMR, and
synchrotron X-ray studies revealed that a subtle change in cation chemistry
results in substantial differences in the thermal phase behavior, crystalline
structures, as well as the ion conduction mechanisms in the protic plastic
crystal compounds. Whereas most of the research nowadays has been focused on the
optimization of chemistry of cations and anions, this work highlights the
importance of microstructures on the ion transport rate and pathways of the OIPC
materials.
PMID- 29953237
TI - One-Pot Peptide Ligation-Oxidative Cyclization Protocol for the Preparation of
Short-/Medium-Size Disulfide Cyclopeptides.
AB - Native chemical ligation (NCL) employing the N-methylbenzimidazolinone (MeNbz)
linker readily provided the linear precursor of a 16-mer peptide that is
difficult to obtain by stepwise solid-phase peptide synthesis. NCL and the workup
conditions were improved toward a protocol that allows for quantitative removal
of the 4-hydroxymercaptophenol additive and subsequent formation of the disulfide
bridge in the NCL cocktail by oxidation in air, tolerated by the presence of
tris(hydroxypropyl)phosphine.
PMID- 29953238
TI - Synthesis of Alkyl Citrates (-)-CJ-13,981, (-)-CJ-13,982, and (-)-L-731,120 via a
Cyclobutene Diester.
AB - An efficient and step-economic new approach to alkyl citrate natural products
from a cyclobutene diester is presented. The key sequence involves a formal [2 +
2]-cycloaddition of a silylketene acetal with dimethylacetylene dicarboxylate to
provide the cyclobutene diester 14 with 4.5:1 stereoselectivity. Exposure of
diester 14 in acidic methanol effected a hydrolysis, intramolecular oxy-Michael
reaction, and cyclobutanone methanolysis cascade to give the triester 15.
Iodination and elimination then afforded a key alkyl citrate alkene intermediate,
which was converted into the natural products (-)-CJ-13,982 (1), (-)-CJ-13,981
(2), and (-)-L-731,120 (3) via a cross-metathesis and subsequent reduction.
PMID- 29953239
TI - Field-Free Spin-Orbit Torque Switching from Geometrical Domain-Wall Pinning.
AB - Spin-orbit torques, which utilize spin currents arising from the spin-orbit
coupling, offer a novel method for the electrical switching of the magnetization
with perpendicular anisotropy. However, the necessity of an external magnetic
field to achieve deterministic switching is an obstacle for realizing practical
spin-orbit torque devices with all-electric operation. Here, we report field-free
spin-orbit torque switching by exploiting the domain-wall motion in an anti
notched microwire with perpendicular anisotropy, which exhibits multidomain
states stabilized by the domain-wall surface tension. The combination of spin
orbit torque, Dzyaloshinskii-Moriya interactions, and domain-wall surface-tension
induced geometrical pinning allows the deterministic control of the domain wall
and offers a novel method to achieve a field-free spin-orbit torque switching.
Our work demonstrates the proof of concept of a perpendicular memory cell that
can be readily adopted in three-terminal magnetic memory.
PMID- 29953240
TI - Copper-Catalyzed Regioselective Intramolecular Electrophilic Sulfenoamination via
Lewis Acid Activation of Disulfides under Aerobic Conditions.
AB - The activation of disulfides by Cu(II) salts has been realized, which triggers a
highly efficient electrophilic sulfenoamination of alkenes under aerobic
conditions. Various sulfenyl N-heterocycles and their Selena counterparts were
produced regioselectively, with no competing disulfidation products detected.
Mechanistic studies suggest a profound influence of the counterions on the Lewis
acidic copper center, and the important roles of oxygen and DMSO as co-oxidants
for these cyclization processes.
PMID- 29953241
TI - From Phenanthrylene Butadiynylene Macrocycles to S-Heterocycloarenes.
AB - The first member of S-heterocycloarenes was synthesized from an easily prepared
phenanthrylene ethynylene macrocycle through diyne cyclocondensation and a Scholl
reaction. The solution-processed thin film of this S-heterocycloarene behaved as
a p-type semiconductor.
PMID- 29953242
TI - Switchable Access to 3-Carboxylate-4-quinolones and 1-Vinyl-3-carboxylate-4
quinolones via Oxidative Cyclization of Isatins and Alkynes.
AB - An efficient transition-metal-free oxidative cyclization reaction using isatins
and alkynes for the facile synthesis of structurally diverse 4-quinolones has
been developed. Intriguingly, switchable access to substituted 3-carboxylate-4
quinolones and 1-vinyl-3-carboxylate-4-quinolones could be achieved by choosing a
different base in the reaction. The obtained products could undergo further
transformations, increasing the application potential of the method in organic
synthesis.
PMID- 29953243
TI - Supramolecular-Surface Photochemistry: Assembly and Photochemistry of Host-Guest
Capsules on Silica Surface.
AB - Host cavitands and organic guest molecules independently adsorbed on silica
particles when mixed and shaken in the presence of a few drops of water underwent
intra- and interparticle migration to form capsular complexes that were not
formed either in water or organic solvents. Importance of cavitand migration and
tumbling on silica surface was established by demonstrating that covalently
linked cavitands do not form capsular complexes. The encapsulated guests
exhibited selective photochemistry as they do within an organic capsule in
solution.
PMID- 29953244
TI - Reverse Triggering Causes an Injurious Inflation Pattern during Mechanical
Ventilation.
PMID- 29953245
TI - Development of a new benchmark for assessing the scoring functions applicable to
protein-protein interactions.
AB - AIM: Scoring functions are important component of protein-protein docking
methods. They need to be evaluated on high-quality benchmarks to reveal their
strengths and weaknesses. Evaluation results obtained on such benchmarks can
provide valuable guidance for developing more advanced scoring functions.
Methodology & results: In our comparative assessment of scoring functions for
protein-protein interactions benchmark, the performance of a scoring function was
characterized by 'docking power' and 'scoring power'. A high-quality dataset of
273 protein-protein complexes was compiled and employed in both tests. Four
scoring functions, including FASTCONTACT, ZRANK, dDFIRE and ATTRACT were tested
as demonstration. ZRANK and ATTRACT exhibited encouraging performance in the
docking power test. However, all four scoring functions failed badly in the
scoring power test. CONCLUSION: Our comparative assessment of scoring functions
for protein-protein interaction benchmark is created especially for assessing the
scoring functions applicable to protein-protein interactions. It is different
from other benchmarks for assessing protein-protein docking methods. Our
benchmark is available to the public at www.pdbbind-cn.org/download/CASF-PPI/ .
PMID- 29953246
TI - Improving Our Aim: Targeting Therapy with Roflumilast in Patients with Severe and
Very Severe Chronic Obstructive Pulmonary Disease.
PMID- 29953247
TI - The current limits in virtual screening and property prediction.
AB - Beyond finding inhibitors that show high binding affinity to the respective
target, there is the challenge of optimizing their properties with respect to
metabolic and toxicological issues, as well as further off-target effects. To
reduce the experimental effort of synthesizing and testing actual substances in
corresponding assays, virtual screening has become an indispensable toolbox in
preclinical development. The scope of application covers the prediction of
molecular properties including solubility, metabolic liability and binding to
antitargets, such as the hERG channel. Furthermore, prediction of binding sites
and drugable targets are emerging aspects of virtual screening. Issues involved
with the currently applied computational models including machine learning
algorithms are outlined, such as limitations to the accuracy of prediction and
overfitting.
PMID- 29953248
TI - Safety of Extubating Mechanically Ventilated Patients Receiving Vasoactive
Infusions: A Retrospective Cohort Study.
PMID- 29953249
TI - NeuroQuant(r) and NeuroGage(r) reveal effects of traumatic brain injury on brain
volume.
AB - This report describes the case of a 58-year-old man with moderate traumatic brain
injury (TBI) and pre-accident brain disorders who had multiple persistent
neuropsychiatric symptoms. NeuroQuant(r) 2.0 and NeuroGage(r) 2.0 MRI brain
volume analyses were used during the chronic stage of injury (> 1 year after
injury) to help understand the effects of the TBI on his brain volume.
NeuroQuant(r) showed widespread cross-sectional atrophy, especially in the
frontal and temporal lobes, consistent with encephalomalacia seen on the MRIs.
Several of his clinical symptoms were consistent with the volume abnormalities.
NeuroGage(r) longitudinal analyses of volume change from the time 1 to time 2
magnetic resonance imaging showed abnormally rapid atrophy and ventricular
enlargement. The high rates of volume change were much more consistent with the
relatively recent effects of TBI than with effects of the much more chronic pre
accident brain disorders.
PMID- 29953250
TI - All about Pulmonary Hypertension: Echocardiography, Hemodynamics, and Treatment.
PMID- 29953251
TI - Diverse classes of HDAC8 inhibitors: in search of molecular fingerprints that
regulate activity.
AB - AIM: HDAC8 is one of the crucial enzymes involved in malignancy. Structural
explorations of HDAC8 inhibitory activity and selectivity are required. MATERIALS
& METHODS: A mathematical framework was constructed to explore important
molecular fragments responsible for HDAC8 inhibition. Bayesian classification
models were developed on a large set of structurally diverse HDAC8 inhibitors.
RESULTS: This study helps to understand the structural importance of HDAC8
inhibitors. The hydrophobic aryl cap function is important for HDAC8 inhibition
whereas benzamide moiety shows a negative impact on HDAC8 inhibition. CONCLUSION:
This work validates our previously proposed structural features for better HDAC8
inhibition. The comparative learning between the statistical and intelligent
methods will surely enrich future drug design aspects of HDAC8 inhibitors.
PMID- 29953252
TI - Healthcare professional involvement and RTP compliance in high school athletes
with concussion.
AB - OBJECTIVES: To describe concussion rates in high school athletes and involvement
of healthcare professionals in concussion diagnosis, management and compliance
with return to play (RTP) guidelines. METHODS: Data were analysed from injury
reports in the National High School Sports-Related Injury Surveillance System
between 2009/2010 and 2012/2013 to identify student athletes with concussion and
determine compliance with RTP guidelines. Compliance with RTP guidelines was
examined using logistic regression, adjusting for sport and injury-related
variables. RESULTS: There were 5611 concussions recorded during 15 712 475
athlete exposures (AEs), a rate of 3.6 concussions per 10 000 AEs. Rates were
higher during competition and among girls compared to boys in gender equitable
sports. Healthcare professionals were less likely to be present at the time of
concussion for girls' sports, lower competition levels and practices. Compliance
with RTP guidelines was higher for athletes with recurrent concussions, those
sustained in collision sports, for athletes reporting more symptoms and when a
physician made the RTP decision. CONCLUSIONS: Presence of healthcare
professionals and compliance with RTP guidelines varied by sport, gender, level
of play and exposure type. High school athletes with concussion are best served
by assessment teams with athletic trainers and physicians working together to
manage concussions and contribute to RTP decisions.
PMID- 29953254
TI - Identification of novel mRNAs and lncRNAs associated with mouse experimental
colitis and human inflammatory bowel disease.
AB - Inflammatory bowel disease (IBD) is a complex disorder that is associated with
significant morbidity. While many recent advances have been made with new
diagnostic and therapeutic tools, a deeper understanding of its basic
pathophysiology is needed to continue this trend toward improving treatments. By
utilizing an unbiased, high-throughput transcriptomic analysis of two well
established mouse models of colitis, we set out to uncover novel coding and
noncoding RNAs that are differentially expressed in the setting of colonic
inflammation. RNA-seq analysis was performed using colonic tissue from two mouse
models of colitis, a dextran sodium sulfate-induced model and a genetic-induced
model in mice lacking IL-10. We identified 81 coding RNAs that were commonly
altered in both experimental models. Of these coding RNAs, 12 of the human
orthologs were differentially expressed in a transcriptomic analysis of IBD
patients. Interestingly, 5 of the 12 of human differentially expressed genes have
not been previously identified as IBD-associated genes, including ubiquitin D.
Our analysis also identified 15 noncoding RNAs that were differentially expressed
in either mouse model. Surprisingly, only three noncoding RNAs were commonly
dysregulated in both of these models. The discovery of these new coding and
noncoding RNAs expands our transcriptional knowledge of mouse models of IBD and
offers additional targets to deepen our understanding of the pathophysiology of
IBD. NEW & NOTEWORTHY Much of the genome is transcribed as non-protein-coding
RNAs; however, their role in inflammatory bowel disease is largely unknown. This
study represents the first of its kind to analyze the expression of long
noncoding RNAs in two mouse models of inflammatory bowel disease and correlate
them to human clinical samples. Using high-throughput RNA-seq analysis, we
identified new coding and noncoding RNAs that were differentially expressed such
as ubiquitin D and 5730437C11Rik.
PMID- 29953253
TI - Lipid malabsorption from altered hormonal signaling changes early gut microbial
responses.
AB - Infants with congenital diarrheal disorders caused by enteroendocrine cell
dysgenesis, or the loss of intestinal endocrine cells, causes severe
malabsorptive diarrhea, though the mechanism is not fully understood. The
transcription factor "aristaless-related homeobox" (Arx) is specifically
expressed in intestinal endocrine cells. This study seeks to characterize the
early malabsorptive phenotype of mice deficient for Arx using cell-type specific
gene ablation in Villin-Cre; ArxloxP/Y ( Arxint) mice. In neonatal mice, the loss
of intestinal Arx caused the loss of intestinal hormones, such as
cholecystokinin, secretin, neurotensin, glucose-dependent insulinotropic peptide,
glucagon-like peptide (GLP)-1 and GLP-2 but also upregulation of somatostatin.
Arxint mice exhibited steatorrhea with the loss of lipid transport in duodenal
enterocytes, upregulation of lysozyme-positive Paneth cells, and a secondary
increase in antimicrobial peptides, specifically Reg3beta. When the epithelium
from Arxint mice was cultured ex vivo into enteroids, however, the Reg3beta
upregulation was lost under the sterile conditions. Thus, Arx is required for the
appropriate lineage allocation of multiple enteroendocrine subtypes. We concluded
that altered hormonal signaling caused by Arx deficiency results in lipid
malabsorption, premature Paneth cell differentiation, and an inflammatory
response, including neutrophilic infiltrates and a microbiota-triggered
upregulation of Reg3beta. NEW & NOTEWORTHY The enteroendocrine transcription
factor aristaless-related homeobox (Arx) plays a key role in lineage
specification. Changes in hormonal expression mediated by Arx lead to lipid
malabsorption and premature Paneth cell development. Furthermore, global
profiling of whole intestine from Arx-deficient mice revealed significant
upregulation of antimicrobial peptides. This antimicrobial response in Arx
deficient animals is lost under sterile culture conditions of enteroids.
PMID- 29953255
TI - Liver chemoembolization of hepatocellular carcinoma using TANDEM(r) microspheres.
AB - Transarterial chemoembolization (TACE) combines intra-arterial delivery of a
chemotherapeutic agent with selective embolization to obtain a synergistic
effect. TACE is recognized as the standard treatment of hepatocellular carcinoma
patients at an intermediate stage. If conventional TACE, defined as the injection
of an emulsion of a drug with ethiodized oil, still has a role to play, the
development of drug-eluting beads has allowed many improvements and optimization
of the technique. TANDEM(r) microspheres are second-generation drug-loadable
microspheres. This device raised a special interest due to its tightly calibrated
spherical microspheres, with small sizes down to 40 MUm available. In this
review, we describe the technical characteristics of these microspheres, analyze
the scientific literature and hypothesize on the future perspectives.
PMID- 29953256
TI - Structurally Unsound? Why Airways Become Asthmatic.
PMID- 29953257
TI - Targeted Delivery and Tolerability of MRI-Guided CED Infusion into the Cerebellum
of Nonhuman Primates.
AB - This study explored the feasibility of intraparenchymal delivery (gadoteridol
and/or Serotype 5 Adeno-Associated Viral Vector-enhanced Green Fluorescent
Protein [AAV5-eGFP]) into the cerebellum of nonhuman primates using real-time
magnetic resonance imaging-guided convection enhanced delivery (MRI-CED)
technology. All animals tolerated the neurosurgical procedure without any
clinical sequela. Gene expression was detected within the cerebellar parenchyma
at the site of infusion and resulted in transduction of neuronal cell bodies and
fibers. Histopathology indicated localized damage along the stem of the cannula
tract. These findings demonstrate the potential of real-time MRI-CED to deliver
therapeutics into the cerebellum, which has extensive reciprocal connections and
may be used as a target for the treatment of neurological disorders.
PMID- 29953258
TI - Effect of Fatigue on Medial Elbow Torque in Baseball Pitchers: A Simulated Game
Analysis.
AB - BACKGROUND: The incidence of overuse injury to the elbow among baseball pitchers
continues to rise, despite extensive efforts at pitch count regulations and
emphasis on proper throwing mechanics. PURPOSE: To determine if the medial elbow
experiences increased torque levels as a baseball pitcher fatigues through the
course of a simulated game. STUDY DESIGN: Descriptive laboratory study. METHODS:
High school and collegiate baseball pitchers were recruited for this simulated
game study. Each pitcher completed a simulated game consisting of 6 innings and a
standardized pitching scheme of fastballs, curveballs, and changeups. In total,
each pitcher threw 90 pitches. Fatigue was reported per inning with a visual
analog scale, and pitch velocity was captured per pitch with a radar gun. Outcome
measures were assessed with a validated mobile sensor and included medial elbow
torque, arm speed, arm rotation, and arm slot. Linear and quadratic regression
modeling was used to evaluate the relationship between pitcher fatigue and
pitching kinematics. RESULTS: A total of 11 pitchers (mean age, 17.6 years;
range, 15-20 years) completed the study. Visual analog scale fatigue scores
increased 0.72 points per inning pitched ( P < .01, effect size = 0.64). Medial
elbow torque also increased beyond inning 3, with an increase of 0.84 N.m each
inning ( P < .01, effect size = 0.08), while pitch velocity decreased (0.28 mph
per inning, P < .01, effect size = 0.27). Fastballs generated the greatest amount
of medial elbow torque (49.3 +/- 1.4 N.m, P < .01, effect size = 0.24). There
were no differences in arm rotation ( P = .42) or arm speed ( P = .80) as the
game progressed. However, arm slot decreased with each successive inning (0.73
degrees on average per inning, P = .03, effect size = 0.12). No adverse outcomes
were noted with use of the mobile sensor. CONCLUSION: In this simulated game
analysis, pitchers experienced increased fatigue after each successive inning.
While the average pitch velocity declined with each successive inning, the torque
on the medial elbow increased after inning 3. These findings signify a possible
relationship between fatigue and injury risk.
PMID- 29953259
TI - Delineating the Cellular Mechanisms Associated with Skin Electroporation.
AB - The immune responses elicited following delivery of DNA vaccines to the skin has
previously been shown to be significantly enhanced by the addition of
electroporation (EP) to the treatment protocol. Principally, EP increases the
transfection of plasmid DNA (pDNA) into the resident skin cells. In addition to
increasing the levels of in vivo transfection, the physical insult induced by EP
is associated with activation of innate pathways which are believed to mediate an
adjuvant effect, further enhancing DNA vaccine responses. We investigated the
possible mechanisms associated with this adjuvant effect, primarily focusing on
the cell death pathways associated with the skin EP procedure independent of pDNA
delivery. Using the minimally invasive CELLECTRA(r)-3P intradermal
electroporation device that penetrates the epidermal and dermal layers of the
skin, we have investigated apoptotic and necrotic cell death in relation to the
vicinity of the electrode needles and electric field generated. Employing the
well-established terminal deoxynucleotidyl transferase nick-end labeling assay,
we detected apoptosis beginning as early as one hour after EP and peaking at the
4 h time point. The majority of the apoptotic events were detected in the
epidermal region directly adjacent to the electrode needle. Using a novel
propidium iodide in vivo necrotic cell death assay, we detected necrotic events
concentrated in the epidermal region adjacent to the electrode. Furthermore, we
detected upregulation of calreticulin expression on skin cells after EP, thus
labeling these cells for uptake by dendritic cells and macrophages. These results
allow us to delineate the cell death mechanisms occurring in the skin following
intradermal EP independently of pDNA delivery. We believe these events contribute
to the adjuvant effect observed following electroporation at the skin treatment
site.
PMID- 29953260
TI - Confident application of a global human liver microsomal activity QSAR.
AB - : Metabolic stability is an important property of drug candidates and
pharmaceutical companies often have human liver microsomal (HLM) data for a large
number of molecules, enabling development of global quantitative structure
activity relationship models. RESULTS: This study describes a strategy for
building a global HLM quantitative structure-activity relationship model,
applicable also to datasets of limited size. By using external congeneric test
sets, a realistic description of the performance in the future applied setting
and a reliable prediction confidence method is obtained. CONCLUSION: The limited
ability of the HLM model to generalize in chemical space to show the importance
of internal model development and continuous updating of global HLM models, as
well as the importance of a validated prediction confidence method.
PMID- 29953262
TI - Autonomic dysregulation in colon cancer patients.
AB - To the best of our knowledge, only two studies analyzed the relationship between
HRV and carcinoembryonic antigen (CEA) in colon cancer patients. The aim of this
study was to analyze changes in the autonomic activity of colon cancer patients
using heart rate variability (HRV) and blood pressure variability (BPV) measures,
and to verify if HRV and BPV parameters correlate with hemodynamic indices in
this group and the plasma levels of CEA. Presence of colon cancer is associated
with changes in autonomic activity, namely parasympathetic-sympathetic imbalance
in form of sympathetic overdrive. Cancer-related autonomic dysfunction may
contribute to impairment of gastrointestinal motility.
PMID- 29953261
TI - Immune Surveillance by Natural IgM Is Required for Early Neoantigen Recognition
and Initiation of Adaptive Immunity.
AB - Early recognition of neoantigen-expressing cells is complex, involving multiple
immune cell types. In this study, in vivo, we examined how antigen-presenting
cell subtypes coordinate and induce an immunological response against neoantigen
expressing cells, particularly in the absence of a pathogen-associated molecular
pattern, which is normally required to license antigen-presenting cells to
present foreign or self-antigens as immunogens. Using two reductionist models of
neoantigen-expressing cells and two cancer models, we demonstrated that natural
IgM is essential for the recognition and initiation of adaptive immunity against
neoantigen-expressing cells. Natural IgM antibodies form a cellular immune
complex with the neoantigen-expressing cells. This immune complex licenses
surveying monocytes to present neoantigens as immunogens to CD4+ T cells. CD4+ T
helper cells, in turn, use CD40L to license cross-presenting CD40+ Batf3+
dendritic cells to elicit a cytotoxic T cell response against neoantigen
expressing cells. Any break along this immunological chain reaction results in
the escape of neoantigen-expressing cells. This study demonstrates the
surprising, essential role of natural IgM as the initiator of a sequential
signaling cascade involving multiple immune cell subtypes. This sequence is
required to coordinate an adaptive immune response against neoantigen-expressing
cells.
PMID- 29953263
TI - Constant light alters serum hormone levels related to thyroid function in male CD
1 mice.
AB - Disruptions to the circadian rhythm can lead to altered metabolism. Modification
of thyroid function may be a reason why circadian misalignment may contribute to
future metabolic disorders. We investigated whether circadian disruption through
constant light (LL) can lead to variations in hormone levels associated with
thyroid function. Mice were exposed to LL or a 12:12 Light:Dark (LD) cycle for 6
weeks; then glucose tolerance and thyroid hormone levels were measured at ZT 6
and ZT 18. There was day/night variation in glucose tolerance, but LL had no
effect. LL reduced TSH, increased fT4, and abolished day/night variation in fT3
and leptin. These findings illustrate that LL alters thyroid-related hormones,
providing evidence of a link between circadian disruption and thyroid function.
PMID- 29953264
TI - Intra-aortic balloon pump: current evidence & future perspectives.
AB - The intra-aortic balloon pump (IABP) is frequently used to support severely
compromised ventricles in critically ill patients. Its relatively affordability
and ease of insertion has cemented its position as the first line of treatment
for hemodynamic support in cardiogenic shock. Accordingly, the current ACC/AHA
recommendations maintain a Class 2A for the use of IABP in shock. However, a
review of the current literature suggests that the evidence supporting the
American College of Cardiology and American Heart Association (ACC/AHA)
guidelines are equivocal. Alternative uses for IABP such as perioperative support
during high-risk cardiac surgery, treatment of left ventricular distention on
extracorporeal membrane oxygenation, and as bridge to transplant have been
proposed. The effectiveness of the IABP in these clinical situations remains
largely unproven, due to the paucity of available data.
PMID- 29953265
TI - Biological rhythms, chronodisruption and chrono-enhancement: The role of physical
activity as synchronizer in correcting steroids circadian rhythm in metabolic
dysfunctions and cancer.
AB - Rhythms can be observed at all levels of the biologic integration in humans. The
observation that a biological or physiological variable shows a circadian rhythm
can be explained by several multifactorial systems including external
(exogenous), internal (endogenous) and psychobiological (lifestyle) mechanisms.
Our body clock can be synchronized with the environment by external factors,
called "synchronizers", i.e. the light-dark cycle, but it is also negatively
influenced by some pathological conditions or factors, called "chronodisruptors,"
i.e. aging or low physical activity (PA). The desynchronization of a 24-h rhythm
in a chronic manner has been recently defined "chronodisruption" or "circadian
disruption." A very large number of hormonal variables, such as adrenal and
gonadal stress steroids, are governed by circadian rhythmicity. Such hormones, in
normal conditions, show a peak in the first part of the day, while their typical
diurnal fluctuations are totally out of sync in subjects affected by cancer or
metabolic diseases, such as obesity, diabetes and metabolic syndrome. In general,
a flatter slope with altered peaks in cortisol and testosterone circadian rhythms
has been observed in pathological individuals. PA, specifically chronic exercise,
seems to play a key role as synchronizer for the whole circadian system in such
pathologies even if specific data on steroids circadian pattern are still sparse
and contradictory. Recently, it has been proposed that low-intensity chronic PA
could be an effective intervention to decrease morning cortisol levels in
pathological subjects. The standardization of all confounding factors is needed
to reach more clear evidence-based results.
PMID- 29953266
TI - Recommended standards for assessing blood pressure in human research where blood
pressure or hypertension is a major focus.
AB - BACKGROUND: Although inaccurate, non-reproducible blood pressure values can
result from non-standardized assessments, recommended approaches to standardize
blood pressure measurement are often not followed in research studies. METHODS:
An expert consensus of national and international health and scientific
organizations developed recommended minimum standards for assessing blood
pressure in research subjects where: 1) blood pressure or hypertension is a major
endpoint, or 2) blood pressure is likely a major mediator of the research
outcome. RESULTS: Minimum research standards are presented for training of
observers, technical aspects of assessing blood pressure, and equipment for both
adults and children. LIMITATIONS: The standards are based on prior
recommendations some of which did not conform to the current evidence based
methods. CONCLUSIONS: All new research should require adherence to these minimum
standards on the patient populations described above. Readers need to use caution
in interpreting studies if the standards are not met in the defined populations.
PMID- 29953267
TI - Genetic screening for Bartter syndrome and Gitelman syndrome pathogenic genes
among individuals with hypertension and hypokalemia.
AB - PURPOSE: Bartter syndrome (BS) and Gitelman syndrome (GS) are hereditary diseases
characterized by hypokalemia with decreased or normal blood pressure (BP).
However, BS or GS patients who present with elevated BP levels have been
increasingly reported recently. Therefore, this study aimed to investigate the
presence of BS and GS among individuals with unexplained hypokalemia with
hypertension in a clinical setting. METHODS: Patients presented with unexplained
hypertension and hypokalemia admitted to Hypertension Center of Fuwai Hospital
from November 2015 to February 2017 were enrolled. High-throughput sequencing for
five BS and GS causative genes were performed. Variants were classified using
American College of Medical Genetics (ACMG) consensus guidelines. RESULTS: Thirty
four patients with unexplained hypertension and hypokalemia were included for
genetic analysis. A total number of 10 rare variants were identified in six
individuals (mutation detection rate, 17.65%). One homozygous variant carried by
one of the 34 patients, KCNJ1 c.941A> G (p.Tyr314Cys), were categorized as likely
pathogenic variant and resulted in a diagnostic yield of 2.94%. Eight of the
remaining nine variants were predicted to be deleterious by >= three
bioinformatics software and may give additional potential diagnostic yields.
CONCLUSIONS: This is the first study performing combined genetic screening for BS
and GS pathogenic genes among individuals with unexplained hypertension and
hypokalemia. Our data suggested that BS or GS may contribute to the etiology of
patients presented with hypertension and hypokalemia. Genetic testing for BS and
GS pathogenic genes are recommended to facilitate precision diagnoses and
targeted treatment.
PMID- 29953268
TI - Sex-dependent correlation between survival and expression of genes related to the
circadian oscillator in patients with colorectal cancer.
AB - Recent evidence supports the important role of the circadian system in cancer
progression in humans. The aim of the present study is to evaluate clock (cry1,
cry2 and per2) and clock-controlled (vascular endothelial growth factor-a, early
growth response protein 1 and estrogen receptor beta) gene expression in
colorectal cancer and adjacent tissue and identify a possible link between
survival of patients and expression of above mentioned genes. The study includes
64 patients of both sexes with previously diagnosed colorectal cancer. RNA was
extracted from the tumor tissue and adjacent parts of the resected colon, and
real-time PCR was used for detection of clock gene expression. Expression of cry2
and per2 was significantly downregulated in tumor tissue compared to adjacent
tissues. After splitting of the cohort according to sex, we detected
downregulated levels of cry2 and per2 in male patients, but not in females.
Splitting of male and female sub-cohorts according to presence of metastases
revealed significant donwregulation of cry2 expression in female patients without
distant metastasis. Better survival rate was associated with low expression of
cry2 in female patients. Moreover, we observed an increase in cry1 expression in
female patients with distant metastases in tumor compared to adjacent tissue.
Accordingly, women with high expression of cry1 in tumor tissue displayed worse
survival, which was not observed in men. Taken together, expression of clock and
clock-controlled genes in tumors of males and females clustered according to
presence of distant metastases correlated with survival analysis. Studied clock
controlled genes also showed sex-dependent changes. Low expression of vegf-a in
tumor correlated with better survival in men but not in women. High expression of
estrogen receptor beta mRNA was related to better survival in women but not in
men. Low expression of vegf-a, egr1 and estrogen receptor beta was associated
with worse survival in women compared to men. Our data indicate sex-dependent
associations between clock and clock-controlled gene expression in cancer tissue
and patient's survival prognosis.
PMID- 29953270
TI - Supporting patients learning to live with diabetes: a phenomenological study.
AB - This article describes a study of the phenomenon of supporting patients who are
learning to live with diabetes, from a diabetes specialist nurse (DSN)
perspective. Guided by principles of reflective lifeworld research, data from six
interviews (four in groups and two individual) with 16 DSNs were analysed. The
results show that, in order to support learning, DSNs use a self-critical
approach with the insight that they should not take over responsibility for their
patients' diabetes. The DSNs support, encourage and challenge the patients to
self-reflect and take responsibility based on patients' own goals and needs. To
provide support, DSNs need to assume a tactful, critically challenging approach,
dare to confront patients' fears and other emotions and have the insight to know
that the responsibility for learning and integration of the condition lies with
the patient. To be able to support patients in this way, it is necessary that the
DSN is mentored and supported in this role.
PMID- 29953271
TI - Fine-bore nasogastric tube feeding: reducing the risks.
PMID- 29953269
TI - Dose to Pelvic Bone Marrow Defined with FDG-PET Predicts for Hematologic Nadirs
in Anal Cancer Patients Treated with Concurrent Chemo-radiation.
AB - PURPOSE: To investigate whether irradiated volume of pelvic active bone marrow
(ACTBM) may predict decreased blood cells nadirs in anal cancer patients
undergoing concurrent chemo-radiation. METHODS: Forty-four patients were analyzed
and pelvic active bone marrow (ACTBM) was characterized employing 18FDG-PET.
Dosimetric parameters on dose-volume histograms were correlated to nadirs with
generalized linear modeling. RESULTS: ACTBM mean dose was significantly
correlated to white blood cell (beta = -1.338; 95%CI: -2.455/-0.221; p = 0.020),
absolute neutrophil count (beta = -1.651; 95%CI: -3.284/-0.183; p = 0.048), and
platelets (beta = -0.031; 95%CI: -0.057/-0.004; p = 0.024) nadirs. Other
dosimetric parameters were found to be correlated (ACTBM-V10,-V20,-V30and-V40).
CONCLUSIONS: 18FDG-PET is able to define active bone marrow and may predict for
decreased blood cells count nadirs.
PMID- 29953272
TI - Life on the other side: moving from clinical nursing to strategic management.
AB - Alan Nobbs reflects on his decision to move into a more strategic nursing role
rather than stay by the bedside, and the feelings of apprehension that followed.
PMID- 29953273
TI - Patient experience: raising a child with primary lymphoedema.
AB - When Joanne Illsley's son, Archie, was diagnosed with primary lymphoedema she
didn't know what it was. In this article, she talks about the journey from
diagnosis to today, and what lies ahead for Archie and his family.
PMID- 29953274
TI - Assessing the impact of change.
AB - Sam Foster, Chief Nurse, Oxford University Hospitals, explains the importance of
quality impact assessments when introducing change in a trust to prevent changes
causing poor patient care.
PMID- 29953275
TI - Nurse-led education for heart failure patients in developing countries.
AB - : Heart failure readmissions are associated with significant morbidity and
mortality. Adequate education on adherence and self-care behaviours can affect
readmission rates positively and nurses are at the frontline of patient
education. Such education is valuable when establishing heart failure programmes
in developing countries, in light of the challenging socioeconomic circumstances
in these. This study aimed to evaluate nurses' heart failure knowledge, to assess
patients' baseline knowledge, and to evaluate the effectiveness of structured
nurse-driven education. METHODS: a total of 131 cardiac centre-based nurses and
30 chronic heart failure patients participated in the study in Kuwait. Patients
were surveyed a second time 3 to 6 months later, while being followed at an
advanced heart failure clinic by dedicated heart failure nurses. RESULTS: the
majority of the nurses (80%) had not received heart failure education previously,
although they were able to recognise most heart failure symptoms. Significant
improvement in patients' knowledge was noted between the initial and follow-up
surveys. CONCLUSION: establishing a dedicated advanced heart failure programme to
care for patients in a developing country can result in significant improvement
in disease awareness and self-care behaviours when led by well-trained heart
failure nurses. More research is needed to determine if these findings are shared
by other countries in the Middle-East and other developing countries.
PMID- 29953276
TI - Do nasal bridles improve nutritional delivery in patients with feeding tubes?
PMID- 29953277
TI - Nutrition: reducing the hypermetabolic response to thermal injury.
AB - Nutritional support is seen as a vital component in the battle to attenuate the
extreme hypermetabolic response experienced by patients suffering from large
thermal injuries. Protein catabolism precipitating protein malnutrition places
patients at greater risk of wound infection and sepsis due to delayed wound
healing. Underfeeding, aggressive feeding, feeding routes, timing of initiation
of feeding and tight insulin control have all been explored extensively in the
quest to understand what nutritional treatment will best attenuate the
hypermetabolic response. Despite this it is suggested that the majority of
patients with large thermal injuries do not receive adequate nutritional support
immediately post injury. Nurses have a pivotal role to play in ensuring that
thermal injury patients receive appropriate nutritional support based on the best
available evidence.
PMID- 29953278
TI - Assessing vitamin D deficiency.
PMID- 29953279
TI - Chronic heart failure nursing: integrated multidisciplinary care.
AB - Heart failure is a condition that is increasing in prevalence in the UK, with
high patient mortality rates and frequent hospital admissions. Nurse-led heart
failure services help to improve patient outcomes through aiding pharmacological,
interventional and holistic care. Heart failure management teams that work to
support patients can vary greatly from service to service. This article discusses
the evidence and guidelines supporting an integrated multidisciplinary approach
to chronic heart failure nursing care.
PMID- 29953280
TI - Patient safety and hospital accident and emergency services.
AB - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
University, discusses a recent publication by the CQC and some court cases on
hospital A&E services.
PMID- 29953281
TI - Limitations of track and trigger systems and the National Early Warning Score.
Part 2: sensitivity versus specificity.
AB - The second article on the use of track and trigger scoring (TTS) and National
Early Warning Scoring Systems (NEWS 1 and 2) discusses how their use in relation
to some patients can be too sensitive and in the case of others it merely detects
late deterioration. This raises concerns that TTS and NEWS focus on a single set
of observations at one point in time. They, therefore, ignore the observational
trends by failing to compare the latest readings against previous sets of vital
signs. It is therefore important that nurses do not rely solely on these tools,
but use them in conjunction with their physiological knowledge and clinical
assessment to identify deteriorating patients, as well as those who do not
require unnecessary escalation of care.
PMID- 29953282
TI - Joining the digital revolution.
PMID- 29953283
TI - Problems affecting the continuing professional development of nurses.
AB - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
the difficulties nurses have in accessing continuing professional development, as
highlighted by a Royal College of Nursing report.
PMID- 29953286
TI - The Frequent Flyer Periodic Table and an "Element" of Hematology.
PMID- 29953284
TI - From staff nurse to nurse consultant: Continuing professional development part 3:
Assessing your needs.
AB - John Fowler, Educational Consultant, explores continued professional development
for the clinically based nurse, looking at making the most of opportunities.
PMID- 29953287
TI - Tissue-Engineered Total Meniscus Replacement With a Fiber-Reinforced Scaffold in
a 2-Year Ovine Model.
AB - BACKGROUND: Meniscus injuries and associated meniscectomies cause patients long
term pain and discomfort and can lead to joint deterioration. PURPOSE: To
evaluate a collagen-hyaluronan sponge reinforced with synthetic resorbable
polymer fiber for total meniscus reconstruction in a long-term ovine model. STUDY
DESIGN: Controlled laboratory study. METHODS: Eleven skeletally mature sheep were
implanted with the total meniscus scaffold. At 2 years, explants were evaluated
biologically (radial/circumferential histology, immunofluorescence) and
mechanically (compression, tension), and articular surfaces were examined for
damage. RESULTS: The fiber-reinforced scaffold induced formation of functional
neomeniscus tissue that was intact in 8 of 11 animals. The implant was remodeled
into organized circumferentially aligned collagen bundles to resist meniscus hoop
stresses. Moreover, type II collagen and proteoglycan deposition near the inner
margin suggested a direct response to compressive stresses and confirmed
fibrocartilage formation. Cartilage damage was observed, but end-stage (severe)
joint deterioration associated with meniscectomy was avoided, even with
limitations regarding the ovine surgical procedure and postoperative care.
CONCLUSION: A fiber-reinforced total meniscus replacement device induces
formation of functional neomeniscus tissue that has the potential to prevent
catastrophic joint deterioration associated with meniscectomy. CLINICAL
RELEVANCE: An off-the-shelf meniscus device that can be remodeled into functional
tissue and thus prevent or delay the onset of osteoarthritis could address a
widespread clinical need after meniscus injury.
PMID- 29953288
TI - Randomized Controlled Trial of Hip Arthroscopy Surgery vs Physical Therapy:
Response.
PMID- 29953289
TI - Randomized Controlled Trial of Hip Arthroscopy Surgery vs Physical Therapy:
Letter to the Editor.
PMID- 29953291
TI - The Influence of Graft Tensioning Sequence on Tibiofemoral Orientation During
Bicruciate and Posterolateral Corner Knee Ligament Reconstruction: A
Biomechanical Study.
AB - BACKGROUND: During multiple knee ligament reconstructions, the graft tensioning
order may influence the final tibiofemoral orientation and corresponding knee
kinematics. Nonanatomic tibiofemoral orientation may result in residual knee
instability, altered joint loading, and an increased propensity for graft
failure. PURPOSE: To biomechanically evaluate the effect of different graft
tensioning sequences on knee tibiofemoral orientation after multiple knee
ligament reconstructions in a bicruciate ligament (anterior cruciate ligament
[ACL] and posterior cruciate ligament [PCL]) with a posterolateral corner (PLC)
injured knee. STUDY DESIGN: Controlled laboratory study. METHODS: Ten nonpaired,
fresh-frozen human cadaveric knees were utilized for this study. After
reconstruction of both cruciate ligaments and the PLC and proximal graft
fixation, each knee was randomly assigned to each of 4 graft tensioning order
groups: (1) PCL -> ACL -> PLC, (2) PCL -> PLC -> ACL, (3) PLC -> ACL -> PCL, and
(4) ACL -> PCL -> PLC. Tibiofemoral orientation after graft tensioning was
measured and compared with the intact state. RESULTS: Tensioning the ACL first
(tensioning order 4) resulted in posterior displacement of the tibia at 0 degrees
by 1.7 +/- 1.3 mm compared with the intact state ( P = .002). All tensioning
orders resulted in significantly increased tibial anterior translation compared
with the intact state at higher flexion angles ranging from 2.7 mm to 3.2 mm at
60 degrees and from 3.1 mm to 3.4 mm at 90 degrees for tensioning orders 1 and
2, respectively (all P < .001). There was no significant difference in
tibiofemoral orientation in the sagittal plane between the tensioning orders at
higher flexion angles. All tensioning orders resulted in increased tibial
internal rotation (all P < .001). Tensioning and fixing the PLC first (tensioning
order 3) resulted in the most increases in internal rotation of the tibia: 2.4
degrees +/- 1.9 degrees , 2.7 degrees +/- 1.8 degrees , and 2.0 degrees +/-
2.0 degrees at 0 degrees , 30 degrees , and 60 degrees , respectively.
CONCLUSION: None of the tensioning orders restored intact knee tibiofemoral
orientation. Tensioning the PLC first should be avoided in bicruciate knee
ligament reconstruction with concurrent PLC reconstruction because it
significantly increased tibial internal rotation. We recommend that the PCL be
tensioned first, followed by the ACL, to avoid posterior translation of the tibia
in extension where the knee is primarily loaded during most activities. The PLC
should be tensioned last. CLINICAL RELEVANCE: This study will help guide surgeons
in decision making for the graft tensioning order during multiple knee ligament
reconstructions.
PMID- 29953292
TI - Corrigendum.
AB - Blasiak A, Whyte GP, Matlak A, Brzoska R, Sadlik B. Morphologic properties of
cartilage lesions in the knee arthroscopically prepared by the standard curette
technique are inferior to lesions prepared by specialized chondrectomy
instruments. Am J Sports Med. 2018;46(4):908-914. (Original DOI:
10.1177/0363546517745489) There is an error in the Abstract of this article. The
Conclusion of the Abstract currently reads: Arthroscopic cartilage lesion
preparation with SC instruments results in superior perpendicularity of
surrounding cartilage walls to subchondral bone and greater consistency of
debrided lesion depth, as compared with the standard debridement technique with
curettes. It should have read: Arthroscopic cartilage lesion preparation with CM
instruments results in superior perpendicularity of surrounding cartilage walls
to subchondral bone and greater consistency of debrided lesion depth, as compared
with the standard debridement technique with curettes.
PMID- 29953293
TI - The Effectiveness of Platelet-Rich Plasma Injections in Gluteal Tendinopathy:
Response.
PMID- 29953295
TI - Moving Toward Responsible Use of Biologics in Sports Medicine.
PMID- 29953294
TI - The Effectiveness of Platelet-Rich Plasma Injections in Gluteal Tendinopathy:
Letter to the Editor.
PMID- 29953296
TI - Double-Bundle Posterior Cruciate Ligament Reconstruction in 100 Patients at a
Mean 3 Years' Follow-up: Outcomes Were Comparable to Anterior Cruciate Ligament
Reconstructions.
AB - BACKGROUND: Historically, outcomes of posterior cruciate ligament (PCL)
reconstructions have been less predictable and reported to yield inferior results
when compared with those for anterior cruciate ligament (ACL) reconstructions.
PURPOSE: To report on the outcomes of double-bundle PCL reconstructions (DB
PCLRs) in isolated versus combined injuries and acute versus chronic PCL
reconstructions. To compare the outcomes of isolated DB PCLR with isolated ACL
reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All
patients who underwent a primary endoscopic DB PCLR for complete PCL tears (grade
III) between May 2010 and March 2015 were reviewed. Patient-reported outcome
scores (Tegner, Lysholm, WOMAC [Western Ontario and McMaster Universities
Osteoarthritis Index], SF-12 [12-item Short Form Health Survey]) and objective
posterior stress radiographs were collected preoperatively and at a minimum 2
years postoperatively. A cohort subanalysis was additionally performed between
isolated and combined PCL reconstruction and acute versus chronic PCL
reconstruction. Patients who underwent isolated ACL reconstructions over the same
inclusion period (2010-2015) were selected as a comparison group. RESULTS: One
hundred patients who underwent DB PCLR were included in this study. There were 31
isolated PCL injuries, and 69 patients had concurrent combined PCL injuries
requiring surgery. The mean follow-up for the PCL cohort was 2.9 years (range, 2
6 years). The median Tegner activity score improved from 2 to 5, Lysholm from 48
to 86, WOMAC from 35.5 to 5, and SF-12 Physical Component Summary from 34 to 54.8
(all P values <.001). The mean side-to-side difference in posterior tibial
translation on kneeling stress radiographs improved from 11.0 +/- 3.5 mm
preoperatively to 1.6 +/- 2.0 mm postoperatively ( P < .001). There were no
differences in postoperative functional scores between isolated PCL
reconstructions and PCL-based multiligament reconstructions (all P values >.229).
There was no significant difference in the reported outcome scores between acute
and chronic reconstructions (all P values >.087) except for Tegner scores ( P <
.001) and patient satisfaction ( P = .011) favoring acutely treated PCL injuries.
There were no significant differences between patients who had an isolated DB
PCLR and patients who underwent an isolated ACL reconstruction (n = 141) in
postoperative outcome scores (all P values >.064). CONCLUSION: Significantly
improved functional and objective outcomes were observed after anatomic DB PCLR
at a mean 3 years' follow-up, with low complication rates, regardless of
concomitant ligamentous injury or timing to surgery. Additionally, contrary to
previous reports, comparable subjective and functional clinical outcomes were
achieved compared with an isolated ACL reconstruction control cohort.
PMID- 29953297
TI - Influence of Exogenous beta-Hydroxybutyrate on Walking Economy and Rating of
Perceived Exertion.
AB - This study investigates the effect of a supplementary ketone, beta
hydroxybutyrate (BHB), on walking economy and ratings of perceived exertion in
apparently healthy individuals. In a repeated-measures, crossover design, ten non
aerobically trained participants (three males; seven females) performed two
stages of a duration-modified Bruce treadmill protocol. Participants blindly
consumed either 1 ounce of an exogenous BHB solution (KETO) or a noncaloric
placebo (CON) 30 minutes prior to exercise testing. Blood ketone and glucose
concentrations were measured prior to supplementation (baseline), immediately
before exercise, and after exercise. Oxygen consumption (VO2), respiratory
exchange ratio (RER), energy expenditure (EE), and rating of perceived exertion
(RPE) were recorded during the last two minutes of each stage. Blood BHB
concentrations were significantly elevated at the pre-exercise and postexercise
time points as compared to the CON condition (p < .001), and blood glucose was
significantly elevated postexercise in both conditions as compared to baseline
levels (p < .001). No significant between-trial differences (p > .05) were found
for VO2, RER, EE, or RPE. The intervention of this study did not produce evidence
of an ergogenic benefit from BHB supplementation in a healthy subject pool.
PMID- 29953298
TI - High throughput discovery and characterization of tick and pathogen vaccine
protective antigens using vaccinomics with intelligent Big Data analytic
techniques.
AB - INTRODUCTION: The incidence of tick-borne diseases (TBDs) is growing worldwide,
and vaccines appear as the most effective and environmentally sound intervention
for the prevention and control of TBDs. Areas covered: The vaccinomics approach
combines omics technologies and bioinformatics for the characterization of tick
host-pathogen molecular interactions and the development of next-generation
vaccines. The two main challenges of the vaccinomics approach are the integration
and analysis of omics datasets, and the development of screening platforms for
the identification of candidate protective antigens. To address these challenges
we propose the application of intelligent Big Data analytic techniques for the
high throughput discovery and characterization of tick and pathogen derived
candidate vaccine protective antigens. Expert commentary: This innovative
approach should improve the development and efficacy of vaccines for the control
and prevention of TBDs.
PMID- 29953299
TI - Berberis aristata Ameliorates Testicular Toxicity Induced by Combination of First
Line Tuberculosis Drugs (Rifampicin + Isoniazid + Pyrazinamide) in Normal Wistar
Rats.
AB - First-line antituberculosis drugs, namely, isoniazid (INH), rifampicin (RIF), and
pyrazinamide (PZA), contribute to diverse pathological complications. Testicular
toxicity is one such complication. Berberis aristata DC is an herb with
potentially curative characteristics. The aim of this study was to test whether
extract of Berberis aristata DC (Berberidaceae) has curing potential against
testicular toxicity. Characterization of extract was done using ultra-performance
liquid chromatography along with acute toxicity testing. Antioxidant activity of
extract was checked by DPPH inhibition assay and H2O2 scavenging assay. Rats were
dosed once daily for 28 days in groups: control group (saline), toxicant group
(30.85 mg/kg body weight INH + 61.7 mg/kg body weight RIF + 132.65 mg/kg body
weight PZA), treatment groups (TB drugs + 150/300 mg/kg body weight extract) and
standard group (TB drugs +100 mg/kg body weight silymarin). Spectrophotometric
evaluations of lipid peroxidation (LPO), reduced glutathione (GSH), superoxide
dismutase (SOD), glutathione-S-transferase (GST), and catalase (CAT) content in
testes were done using standard protocols. DNA fragmentation and
histopathological studies were performed to check the damage at the cellular
level. Acute toxicity studies revealed LD50 > 5 g/Kg body weight of B. aristata
extract. IC50 for DPPH free-radical scavenging activity and H2O2 scavenging assay
were 44.78 ug/mL and 85.28 ug/mL, respectively. Results revealed significant
increase in thiobarbituric acid reactive substances, decrease in glutathione and
different antioxidants levels, DNA fragmentation pattern, and changes in
histology in toxicant group. All the changes were absent in high-dose (300 mg/kg
body weight) extract treatment group. This work proved that B. aristata extract
has protective efficacy against testicular damage caused by anti-TB drugs.
PMID- 29953300
TI - Multimodal Imaging of Post-Infectious Unilateral Outer Retinopathy and
Choroiditis.
AB - PURPOSE: To describe with multimodal imaging a case of post-infectious unilateral
outer retinopathy with choroiditis. METHODS: Retrospective chart review of a case
of a 67-year old male who presented following the onset of viral symptoms with an
acute onset outer retinopathy, small vessel leakage on fluorescein angiography,
and choroidal involvement evident on indocyanine green angiography and near
infrared fundus autofluorescence (NIR-AF). Work up for infectious and autoimmune
etiologies was negative. RESULTS: Treatment with IV methylprednisolone followed
by high dose oral prednisone resulted in improvement in visual acuity, outer
retinal reconstitution and resolution of the choroidal changes. CONCLUSIONS:
Despite this presentation sharing features with both acute zonal occult outer
retinopathy (AZOOR) and multifocal choroiditis (MFC), the case is highly atypical
of both entities.
PMID- 29953301
TI - Macroscopic Evaluation of the Trimmed Frozen Block Is a Helpful Tool for
Intraoperative Assessment of Resection Margins of Breast Cancer Specimens.
AB - INTRODUCTION: The evaluation of the trimming surfaces (TS) of tissue blocks from
frozen sections may serve as a supplementary examination tool for the
intraoperative determination of resection margins of breast cancer specimens.
This study aimed at the investigation of the feasibility and reliability of this
technique, which has been described only very rarely in literature. METHODS: Two
observers assessed digital images from TS obtained from 57 resection margins.
Findings were correlated with the diagnosis of the frozen section (FS) alone and
the final diagnosis on formalin-fixed paraffin-embedded (FFPE) material. RESULTS:
The determination of the resection margin on TS was estimated as feasible for all
cases. Interobserver congruence rate for TS was 96% (kappa = 0.81), which was
lower compared with FFPE (100%, kappa = 1.0) but superior to FS (89%, kappa =
0.67). Intraobserver congruence of the 2 reviewers was 96.5% and 93.0% between TS
and FFPE, and 91.1% and 92.5% between FS and FFPE, respectively. The combination
of both intraoperative consultation techniques showed similar congruence but a
slight improvement for the sensitivity (0.75 to 0.875) for the diagnosis of tumor
at the resection margin in FFPE for Reviewer 1 but was unchanged for Reviewer 2.
CONCLUSION: The additional evaluation of TS can be a helpful additional tool for
intraoperative margin assessment of breast cancer specimens, in particular, when
processing artifacts of FS are encountered.
PMID- 29953303
TI - Vogt-Koyanagi-Harada Disease Associated with Hepatitis B Vaccination.
AB - PURPOSE: To report a case of Vogt-Koyanagi-Harada (VKH) disease associated with
hepatitis B vaccination. METHODS: Case report. RESULTS: A 43-year-old Caucasian
male presented with a three-week history of blurry vision, pain, photophobia, and
redness in both eyes. Three days prior to the onset of symptoms, he had received
the hepatitis B virus vaccine. Clinical evaluation revealed multifocal placoid
lesions in the posterior pole, choroidal thickening, and serous macular
detachment. Targeted laboratory investigations were negative for infectious or
autoimmune markers. After treatment with oral corticosteroids, the patient had
resolution of symptoms with near-total recovery of visual function. The patient
later reported systemic findings of hearing loss, tinnitus, and integumentary
changes. A diagnosis of VKH disease was made and inflammation was managed with
oral corticosteroids followed by methotrexate for long-term disease control.
CONCLUSIONS: VKH disease is an inflammatory condition primarily affecting the
choroid, retinal pigment epithelium, and outer retina. The underlying etiology is
unclear, but it can be associated with a viral prodrome suggesting an infectious
trigger in a genetically susceptible individual. Our case suggests that hepatitis
B vaccination may trigger a similar inflammatory response.
PMID- 29953302
TI - Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its
metabolite EXP3174 in rats and its mechanism.
AB - CONTEXT: Ginkgo leaf tablets (GLTs) and losartan are often simultaneously used
for the treatment of hypertension in Chinese clinics. However, the herb-drug
interaction between GLT and losartan is still unknown. OBJECTIVE: This study
investigates the effects of GLT on the pharmacokinetics of losartan and its
metabolite EXP3174 in rats and its potential mechanism. MATERIALS AND METHODS:
The pharmacokinetic profiles of losartan and EXP3174 of orally administered
losartan (10 mg/kg) with or without GLT pretreatment (80 mg/kg/day for 10 days)
in Sprague-Dawley rats were determined. In vitro, the effects of GLT on the
metabolic stability of losartan were investigated with rat liver microsomes.
RESULTS: The Cmax (1.22 +/- 0.25 vs 1.85 +/- 0.37 MUg/mL) and the AUC(0-t) (6.99
+/- 1.05 vs 11.94 +/- 1.79 mg.h/L) of losartan increased significantly (p < 0.05)
with GLT pretreatment, while the Cmax (1.05 +/- 0.19 vs 0.72 +/- 0.12 MUg/mL) of
EXP3174 decreased significantly (p < 0.05) compared to the control. The t1/2 of
losartan was prolonged significantly from 3.94 +/- 0.62 to 4.75 +/- 0.52 h (p <
0.05). The metabolic stability of losartan was increased from 37.4 min to 59.6
min with GLT pretreatment. DISCUSSION AND CONCLUSIONS: The results indicate that
GLT might increase the plasma concentration of losartan and decrease the
concentration of EXP3174 through inhibiting the metabolism of losartan.
PMID- 29953304
TI - Face-to-Face and Internet-Based Mindfulness-Based Cognitive Therapy Compared With
Treatment as Usual in Reducing Psychological Distress in Patients With Cancer: A
Multicenter Randomized Controlled Trial.
AB - Purpose Mindfulness-based cognitive therapy (MBCT) has been shown to alleviate
psychological distress in patients with cancer. However, patients experience
barriers to participating in face-to-face MBCT. Individual Internet-based MBCT
(eMBCT) could be an alternative. The study aim was to compare MBCT and eMBCT with
treatment as usual (TAU) for psychological distress in patients with cancer.
Patients and Methods We obtained ethical and safety approval to include 245
patients with cancer with psychological distress (>= 11 on the Hospital Anxiety
and Depression Scale) in the study. They were randomly allocated to MBCT (n =
77), eMBCT (n = 90), or TAU (n = 78). Patients completed baseline (T0) and
postintervention (T1) assessments. The primary outcome was psychological distress
on the Hospital Anxiety and Depression Scale. Secondary outcomes were psychiatric
diagnosis, fear of cancer recurrence, rumination, health-related quality of life,
mindfulness skills, and positive mental health. Continuous outcomes were analyzed
using linear mixed modeling on the intention-to-treat sample. Because both
interventions were compared with TAU, the type I error rate was set at P < .025.
Results Compared with TAU, patients reported significantly less psychological
distress after both MBCT (Cohen's d, .45; P < .001) and eMBCT (Cohen's d, .71; P
< .001) . In addition, post-treatment prevalence of psychiatric diagnosis was
lower with both MBCT (33% improvement; P = .030) and eMBCT (29% improvement; P =
.076) in comparison with TAU (16%), but these changes were not statistically
significant. Both interventions reduced fear of cancer recurrence and rumination,
and increased mental health-related quality of life, mindfulness skills, and
positive mental health compared with TAU (all Ps < .025). Physical health-related
quality of life did not improve ( P = .343). Conclusion Compared with TAU, MBCT
and eMBCT were similarly effective in reducing psychological distress in a sample
of distressed heterogeneous patients with cancer.
PMID- 29953305
TI - Endometrioid Endometrial Carcinoma With Spindle Cells-Aberrant p16 and p53
Expression.
AB - Endometrioid carcinoma is known for its diverse morphology and may pose a
diagnostic dilemma when it presents with a spindle cell component. We present a
case of a 65-year-old woman with postmenopausal bleeding. Physical examination
showed a mass protruding from the external cervical os. The patient underwent
biopsy followed by hysterectomy. Pathologic examination showed an endometrioid
endometrial carcinoma with spindle cell differentiation arising in an endometrial
polyp, which raised a variety of differential diagnoses. Prior reports of this
tumor type showed nonaberrant immunohistochemical expression of p16 and p53.
However, this case showed p16 and p53 overexpression indicating that there is a
spectrum of these tumors.
PMID- 29953306
TI - The Effect of Topical Ganciclovir and Corticosteroid on Cytomegalovirus Corneal
Endotheliitis in Korean Patients.
AB - PURPOSE: To report long-term outcomes of topical ganciclovir (GCV) and
corticosteroids in Korean patients with cytomegalovirus (CMV) corneal
endotheliitis. METHODS: This retrospective study included 13 eyes from 13
patients with CMV corneal endotheliitis, with a follow-up period of 24.5 +/- 8.2
months. The patients were consistently maintained with topical 2% GCV and 1%
prednisolone acetate eyedrop. RESULTS: All patients demonstrated unilateral
typical coin-shaped keratic precipitates (KPs) or linear KP, and positive CMV
polymerase chain reaction of aqueous humor. After 2 weeks of treatment, all
patients showed decrease of clinical signs. During the follow-up, four patients
developed mild anterior chamber inflammation with increased intraocular pressure
without typical coin-shaped KPs or edema, started to use the initial dose, and
resolved the clinical signs. One patient showed recurrence of corneal edema
twice, and was administered systemic valgancyclovir for 2 weeks upon second
recurrence with resolution of clinical signs. CONCLUSION: Long-term maintenance
therapy with topical GCV and corticosteroids are effective and maintain corneal
endothelial function in Korean patients with CMV endotheliitis.
PMID- 29953308
TI - Complete Blood Cell Count-Derived Inflammation Biomarkers in Men with Age-Related
Macular Degeneration.
AB - PURPOSE: To investigate the role of some blood count-derived inflammation
biomarkers in age-related macular degeneration (AMD). METHODS: Seventy-nine men
with late-stage AMD and 79 male age-matched cataract controls without AMD were
recruited in March-December, 2016. A blood sample was taken. The following blood
cell count-derived indexes were evaluated: neutrophil/lymphocyte ratio (NLR),
derived NLR [dNLR = neutrophils/(white blood cells - neutrophils)],
platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), (neutrophils *
monocytes)/lymphocyte ratio (SIRI), and (neutrophils * monocytes *
platelets)/lymphocyte ratio (AISI). RESULTS: AMD patients had significantly lower
median values of white blood cells, monocytes, neutrophils, platelets, and mean
platelet volume (MPV). Regarding the combined indexes, only AISI was
significantly lower in AMD patients than in controls. Receiver operating
characteristics curve analysis revealed that the ability of AISI and MPV to
predict AMD is poor. CONCLUSION: Results suggests that NLR, dNLR, PLR, MLR, SIRI,
and AISI are unreliable disease biomarkers in men with AMD. Larger scale studies
are necessary to confirm these findings.
PMID- 29953307
TI - Cost-effectiveness analysis of 13-valent pneumococcal conjugate vaccine versus 23
valent pneumococcal polysaccharide vaccine in an adult population in South Korea.
AB - In South Korea, the National Immunization Program offers a 23-valent pneumococcal
polysaccharide vaccine (PPSV23) for the elderly; however, the 13-valent
pneumococcal conjugate vaccine (PCV13) is not included, and vaccination is not
offered to younger, at-risk populations. This study offers a comparative analysis
of PCV13 and PPSV23 in Korea's adults, stratified by age and risk group. A Markov
model with a lifetime horizon was developed from the healthcare perspective. Data
sources included the Health Insurance Review & Assessment Service, Korea Centre
for Disease Control & Prevention and Korean medical institutions. An expert panel
tested data validity. The CAPiTA trial and Cochrane meta-analysis were used to
obtain vaccine effectiveness data. Regardless of co-morbidity, when the
sequential PCV13-PPSV23 strategy was compared to that using PPSV23-only, in
elderly populations, the incremental cost-effectiveness ratio (ICER) was 3,300
USD per quality-adjusted life years (QALY). For the risk group aged >=65 years,
the ICER of the addition of PCV13 over the existing PPSV23-only strategy was
3,404 USD/QALY. However, on replacing PPSV23 with PCV13, for all elderly
populations, an ICER of 1,421 USD/QALY resulted; for the risk group aged >=65
years, the ICER was 1,736 USD/QALY. For the 18-64 year-old risk group, the
sequential PCV13-PPSV23 strategy yielded an ICER of 3,629 USD/QALY over the
PPSV23-only strategy, and 6,643 USD/QALY compared to no vaccination. Thus, the
PCV13->PPSV23 combination strategy for elderly populations was found to be a cost
effective alternative to the current National Immunization Program regardless of
co-morbidity. This finding was the same as that for younger, at-risk populations.
PMID- 29953309
TI - Clinical Features of Scleritis Across the Asia-Pacific Region.
AB - PURPOSE: To examine the spectrum of scleritis in four tertiary institutions
across the Asia-Pacific. METHODS: Clinical records from 354 patients were
reviewed from centers in Australia, Singapore, and India, excluding those with
insufficient data (n = 24). RESULTS: Indian patients presented younger (41.5 +/-
13.4 years) than Australians (50.8 +/- 17.5) and Singaporeans (48.6 +/- 15.9),
with fewer women (49% vs 62%/57%). Diffuse disease was universally most common.
Autoimmune and infectious disease proportions were similar in Australia
(31%/10.3%) and Singapore (27.5%/8.3%) but reversed in India (8.3%/30%).
Necrotizing scleritis was most frequently associated with infection (27.3%).
Presumed ocular tuberculosis accounted for 75% of infectious cases in India.
Posterior scleritis had the highest complication rate (82.4%) and
immunosuppressants used per patient (0.98 +/- 0.31 95% CI). CONCLUSIONS: Clinical
presentations of scleritis vary across the Asia-Pacific, particularly in endemic
regions for tuberculosis such as India, where it affects younger men with a
predominance of nodular and infectious disease.
PMID- 29953310
TI - Regional Differences in the Clinical Manifestation of Ocular Toxoplasmosis
between the Center and Northeast of Argentina.
AB - PURPOSE: To compare the clinical characteristics of patients with active episodes
of ocular toxoplasmosis from three provinces, Misiones, Santa Fe, and Buenos
Aires, Argentina. METHODS: Patients with a diagnosis of ocular toxoplasmosis from
three databases of four tertiary referral uveitis centers were reviewed.
Collected data included presentation of the retinochoroiditis, location of the
active lesions, associated inflammatory ocular signs and complications. RESULTS:
Three hundred thirty-four patients were included in this study. Bilateral
involvement of the ocular disease occurred in 26 patients in Misiones (35.14%),
21 patients (12.8%) in Santa Fe, and 9 patients in Buenos Aires (9.4%) (p <
0.001). Extensive retinitis was observed in 49 patients (66.2%) in Misiones, 39
patients (23.8%) in Santa Fe, and 12 patients (12.5%) in Buenos Aires (p <
0.001). CONCLUSION: The results indicate that there are differences in the
clinical characteristics of ocular toxoplasmosis in patients from Misiones, Santa
Fe, and Buenos Aires.
PMID- 29953311
TI - Detection and Characterization of an Avipoxvirus in a Common Buzzard ( Buteo
buteo) in Italy Using a Multiple Gene Approach.
AB - Poxvirus infections have been reported in domestic, captive, and wild avian hosts
including many raptor species. A wild Common Buzzard ( Buteo buteo) admitted to a
wildlife veterinary clinic in Sardinia, Italy, showed multiple, wart-like
proliferative cutaneous lesions on both legs. Histologically, there was
ballooning degeneration and large intracytoplasmic inclusion bodies consistent
with avipoxvirus (APV) infection. Diagnosis was confirmed by PCR detecting APV
genes: P4b (locus fpv167), P35 (locus fpv140), and partial DNA polymerase.
Phylogenetic analyses were performed to compare the detected virus with a panel
of selected APVs. Analyses of P4b and DNA polymerase assigned the virus to clade
A (fowlpox virus, FWPV), subclade A7, grouping with many other APVs previously
isolated in birds of prey. Further research should highlight the diversity of
avian pox viral strains circulating among common buzzards as well as the
phylogenetic role of locus fpv140 (P35) in comparison with the more-conserved P4b
and DNA polymerase genes.
PMID- 29953312
TI - Porcine Epidemic Diarrhea Virus and Porcine Deltacoronavirus not Detected in
Waterfowl in the North American Mississippi Migratory Flyway in 2013.
AB - Cloacal swab samples collected from 538 migratory waterfowl along the Mississippi
Migratory Bird flyway in 2013 were tested for porcine epidemic diarrhea virus and
porcine deltacoronavirus. Neither virus was detected in any of the samples,
indicating that waterfowl likely did not contribute to the rapid spread of these
viruses within central US.
PMID- 29953313
TI - Health Status of Reintroduced Wood Bison ( Bison bison athabascae): Assessing the
Conservation Value of an Isolated Population in Northwestern Canada.
AB - A central goal for reintroduced populations of threatened wood bison ( Bison
bison athabascae) is to maintain them free of diseases of concern, particularly
bovine tuberculosis (caused by Mycobacterium bovis) and brucellosis (caused by
Brucella abortus). A wood bison population in southwestern Yukon, Canada was
reintroduced into the wild in 1988, but no health assessment has been done since
then. To provide an initial assessment of the health status and, hence, the
conservation value of this population, we serologically tested 31 wood bison
(approximately 3% of the population) for pathogens of interest and obtained
histopathology results for select tissues. We found no evidence of exposure to M.
bovis or Brucella spp., but antibodies were present to bovine parainfluenza virus
3, bovine coronavirus, Leptospira interrogans, and Neospora caninum, with
seroprevalences of 87, 7, 61, and 7% of the tested animals, respectively.
Reintroduced wood bison in southwestern Yukon may be of high value for wood bison
recovery because it is a large and geographically isolated population with no
bacteriologic, histopathologic, or serologic evidence of exposure to Brucella
spp. or M. bovis.
PMID- 29953314
TI - Seroprevalence and Risk Factors of Toxoplasma g ondii in Wild Birds of Punjab
Province, Pakistan.
AB - Toxoplasma gondii is a protozoan parasite of veterinary and human public health
importance for which birds act as an intermediate host. No information is
available about the epidemiology of T. gondii in wild birds of Pakistan. The
present study was designed to determine the seroprevalence and risk factors
associated with T. gondii antibodies in wild birds of District Kasur, Punjab
Province, Pakistan. A total of 200 wild birds of 28 species were captured from
four tehsils (administrative subdistricts of districts) of the district Kasur and
their serum samples screened for the presence of T. gondii antibodies using a
latex agglutination test (LAT; cut-off value: 1:64). Twenty-five (13%) individual
birds and 13 (46%) of the bird species were seropositive for T. gondii
antibodies. There were statistical differences in T. gondii prevalence between
adults and young (15% and 7%, respectively, P=0.001) and healthy and sick (11%
and 50%, respectively, P=0.000) while there were not differences between genders,
sites, urbanicity, and tehsils. The present study provides evidence of T. gondii
antibodies in wild birds of Pakistan.
PMID- 29953315
TI - Isolation of Talaromyces marneffei From the Skin of an Egyptian Mongoose (
Herpestes ichneumon) in Portugal.
AB - We report a case of Talaromyces marneffei skin infection in an Egyptian mongoose
( Herpestes ichneumon) in Portugal. The isolated fungus was identified through
its mycologic characteristics, morphology, and PCR amplification.
PMID- 29953316
TI - Change in Nationwide Incidence of Post-Cataract Surgery Endophthalmitis: Korean
Cohort Study from 2002 to 2013.
AB - PURPOSE: To investigate the change in nationwide incidence of endophthalmitis
following cataract surgery in Korea from 2002 to 2013. METHODS: From a national
sample cohort (n = 1 025 340), cases of postoperative endophthalmitis between
2002 and 2013 were identified. RESULTS: From 70,719 cases of cataract surgery, 49
incidents of endophthalmitis were reported, yielding an incidence of 0.069% (95%
confidence interval [CI], 0.051-0.092%). Overall, the endophthalmitis incidence
decreased from 0.103% in 2002-2005 to 0.045% in 2010-2013, corresponding to an
annually decreasing time-trend (0.902, 95% CI, 0.827-0.984). In diabetic
patients, however, the incidence was 0.128% and did not change (time trend,
1.015; 95% CI, 0.828-1.245). CONCLUSIONS: This study revealed the incidence of
endophthalmitis decreased during a 12-year period, but remained constant in
diabetic patients.
PMID- 29953317
TI - Rational design of heat stable lyophilized rotavirus vaccine formulations.
AB - To develop a safe and efficacious heat-stable rotavirus vaccine, new lyophilized
formulations were developed using rotavirus serotypes constituting RotaTeq(r). A
series of formulation compositions, differing in buffering agents, bulking
agents, cryoprotectants, amino acids and divalent cations, were screened for
their ability to provide stability to rotavirus serotypes during lyophilization
and when stored under elevated temperatures for extended periods. Lead
formulations and lyophilization cycles were further optimized. Stability profiles
of thus optimized formulations showed their ability to retain the potency of
rotavirus for > 36 months at 5 degrees C, 20 months at 37 degrees C, and 7 months
at 45 degrees C. The heat-stable lyophilized rotavirus formulations developed met
the all critical quality attributes for appearance, heat-stability during
storage, moisture content as well as pH, viability and stability after
reconstitution and has great potential to be used as vaccine candidates for
improving access in low-income countries.
PMID- 29953318
TI - Heterogeneous growth bent-cable models for time-to-event and longitudinal data:
application to AIDS studies.
AB - The major limitations of growth curve mixture models for HIV/AIDS data are the
usual assumptions of normality and monophasic curves within latent classes. This
article addresses these limitations by using non-normal skewed distributions and
multiphasic patterns for outcomes of prospective studies. For such outcomes, new
skew-t (ST) distributions are proposed for modeling heterogeneous growth
trajectories, which exhibit not abrupt but gradual multiphasic changes from a
declining trend to an increasing trend over time. We assess these clinically
important features of longitudinal HIV/AIDS data using the bent-cable framework
within a context of a joint modeling of time-to-event process and response
process. A real dataset from an AIDS clinical study is used to illustrate the
proposed methods.
PMID- 29953321
TI - Prospective Student Database: Technological Support for Assessing the
Effectiveness of Graduate Recruitment Activities.
PMID- 29953319
TI - FcgammaRIIIa-dependent IFN-gamma release in whole blood assay is predictive of
therapeutic IgG1 antibodies safety.
AB - Immunomodulatory monoclonal IgG1 antibodies developed for cancer and autoimmune
disease have an inherent risk of systemic release of pro-inflammatory cytokines.
In vitro cytokine release assays are currently used to predict cytokine release
syndrome (CRS) risk, but the validation of these preclinical tools suffers from
the limited number of characterized CRS-inducing IgG1 antibodies and the poor
understanding of the mechanisms regulating cytokine release. Here, we incubated
human whole blood from naive healthy volunteers with four monoclonal IgG1
antibodies with different proven or predicted capacity to elicit CRS in clinic
and measured cytokine release using a multiplex assay. We found that, in contrast
to anti-CD52 antibodies (Campath-1H homolog) that elicited high level of multiple
inflammatory cytokines from human blood cells in vitro, other IgG1 antibodies
with CRS-inducing potential consistently induced release of a single tested
cytokine, interferon (IFN)-gamma, with a smaller magnitude than Campath. IFN
gamma expression was observed as early as 2-4 h after incubation, mediated by
natural killer cells, and dependent upon tumor necrosis factor and FcgammaRIII.
Importantly, the magnitude of the IFN-gamma response elicited by IgG1 antibodies
with CRS-inducing potential was determined by donor FcgammaRIIIa-V158F
polymorphism. Overall, our results highlight the importance of FcgammaRIIIa
dependent IFN-gamma release in preclinical cytokine release assay for the
prediction of CRS risk associated with therapeutic IgG1 antibodies.
PMID- 29953322
TI - Recent Research in Science Teaching and Learning.
PMID- 29953323
TI - Exploring Postsecondary Biology Educators' Planning for Teaching to Advance
Meaningful Education Improvement Initiatives.
AB - This paper attends to challenges for postsecondary science education improvement
initiatives, notably understanding and responding to the realities guiding
educators' teaching practices. We explored 16 postsecondary biology educators'
instructional planning, providing novel insights into why educators select
certain strategies over others, including lecturing. Our findings point to an
array of factors that educators consider, factors that we believe push against
the lecture versus active-learning dichotomy that we hear in some improvement
rhetoric. We recommend professional development experiences (including peer
evaluations of teaching) wherein educators and other proponents for teaching
improvements explicitly explore rationales for teaching, including educators'
considerations of the nature of the discipline (content and concepts and skills
and processes) and students' needs. Educators with less experience with content
were more likely to seek out additional instructional resources during planning,
including other educators. Given this, teaching improvement proponents may want
to offer professional development activities that sync with periodic and planned
teaching assignments that take educators out of their disciplinary knowledge
comfort zone. Disciplinary colleagues might serve as exemplars of planning and
implementing teaching strategies that both convey foundational content and
processes and engage students via evidence-based practices.
PMID- 29953325
TI - Students' Conception of Genetic Phenomena and Its Effect on Their Ability to
Understand the Underlying Mechanism.
AB - Understanding genetic mechanisms affords the ability to provide causal
explanations for genetic phenomena. These mechanisms are difficult to teach and
learn. It has been shown that students sometimes conceive of genes as traits or
as trait-bearing particles. We termed these "nonmechanistic" conceptions of
genetic phenomena because they do not allow the space required for a mechanism to
exist in the learner's mind. In this study, we investigated how ninth- and 12th
grade students' conceptions of genetic phenomena affect their ability to learn
the underlying mechanisms. We found that ninth- and 12th-grade students with
nonmechanistic conceptions are less successful at learning the mechanisms leading
from gene to trait than students with mechanistic conceptions. Our results
suggest that nonmechanistic conceptions of a phenomenon may create a barrier to
learning the underlying mechanism. These findings suggest that an initial
description of a phenomenon should hint at a mechanism even if the mechanism
would be learned only later.
PMID- 29953324
TI - The Lecture Machine: A Cultural Evolutionary Model of Pedagogy in Higher
Education.
AB - The benefits of student-centered active-learning approaches are well established,
but this evidence has not directly translated into instructors adopting these
evidence-based methods in higher education. To date, promoting and sustaining
pedagogical change through different initiatives has proven difficult, but
research on pedagogical change is advancing. To this end, we examine pedagogical
behaviors through a cultural evolutionary model that stresses the global nature
of the issue, the generational time that change requires, and complications
introduced by academic career trajectories. We first provide an introduction to
cultural evolutionary theory before describing our model, which focuses on how
cultural transmission processes and selection events at different career phases
shape not only who teaches in higher education, but also how they choose to
teach. We leverage our model to make suggestions for expediting change in higher
education. This includes reforming pedagogy in departments that produce PhD
students with the greatest chance of obtaining tenure-track positions.
PMID- 29953326
TI - Immunotherapy of Guillain-Barre syndrome.
AB - Guillain-Barre syndrome (GBS), the most common cause of acute neuromuscular
weakness and paralysis worldwide, encompasses a group of acute immune-mediated
disorders restricted to peripheral nerves and roots. Immune-mediated attack of
peripheral nervous system myelin, axons or both is presumed to be triggered by
molecular mimicry, with both cell- and humoral-dependent mechanisms implicated in
disease pathogenesis. Good circumstantial evidence exists for a pathogenic role
for molecular mimicry in GBS pathogenesis, especially with its axonal forms,
providing insights that could guide future immunotherapy. Intravenous
immunoglobulin (IVIg) and plasma exchange (PE) are the most commonly prescribed
immunotherapies for GBS with variable efficacy dependent on GBS subtype, severity
at initial presentation and other clinical and electrophysiologic prognostic
factors. The mechanisms of action of IVIg and PE are not known definitely.
Despite recent significant advances in molecular biology that provide insights
into GBS pathogenesis, no advances in therapeutics or significant improvements in
patient outcomes have occurred over the past three decades. We summarize the
clinical aspects of GBS, its current pathogenesis and immunotherapy, and
highlight the potential of leukocyte trafficking inhibitors as novel disease
specific immunotherapeutic drugs.
PMID- 29953327
TI - L-statistics of absolute differences for quantifying the agreement between two
variables.
AB - In many clinical studies, Lin's (1989) concordance correlation coefficient (CCC)
is a popular measure of agreement for continuous outcomes. Most commonly, it is
used under the assumption that data are normally distributed. However, in many
practical applications, data are often skewed and/or thick-tailed. King and
Chinchilli (2001) proposed robust estimation methods of alternative CCC indices,
and we propose an approach that extends the existing methods of robust estimators
by focusing on functionals that yield robust L-statistics. We provide two data
examples to illustrate the methodology, and we discuss the results of computer
simulation studies that evaluate statistical performance.
PMID- 29953328
TI - Cesium emissions from laboratory fires.
AB - If a radiological incident such as a nuclear power plant accident, a radiological
dispersal device, or detonation of an improvised nuclear device occurs,
significant areas may be contaminated. Initial cleanup priorities would likely
focus on populated areas, leaving the forested areas to pass several seasons
where the overhead canopy materials would fall to the forest floor. In the event
of a wildfire in a radionuclide-contaminated forest, some radionuclides would be
emitted in the air while the rest would remain in the ash. This paper reports on
a laboratory simulation study that examines the partitioning of cesium-133 (a
nonradioactive isotope of cesium) between airborne particulate matter and
residual nonentrained ash when pine needles and peat are doped with cesium. Only
1-2.5% of the doped cesium in pine needles was emitted as particulate matter, and
most of the cesium was concentrated in the particulate fraction greater than 10
um in aerodynamic diameter. For peat fires, virtually all of the cesium remained
in the ash. The results from this study will be used for modeling efforts to
assess potential exposure risks to firefighters and the surrounding public.
Implications: There is a potential for emissions of radionuclides such as cesium
137 from a wildfire over a radionuclide-contaminated forest. This paper reports
on a laboratory simulation study of a wildfire with two types of biomass doped
with nonradioactive cesium. This simulation suggests that only 1-2.5% of the
cesium in the biomass will be emitted from the wildfire, while the rest will
reside in the residual ash. In this study, pine needles were the only contributor
to the air emissions of cesium; duff was not a source of cesium emissions. In
this study, cesium emitted from the simulated wildfire was concentrated in the
particle sizes larger than 10 um.
PMID- 29953329
TI - A simple and low-cost portable paper-based ABO blood typing device for point-of
care testing.
AB - ABO blood group is the most important blood type system for transfusion medicine.
A paper-based analytical device (PAD) for ABO blood typing has been proposed. The
device was composed of Whatman No. 113 paper, an absorbent gel pad, and a 3D
printing cassette. The 3D-printing cassette contained two circular holes for
display of letters "A" and "B" on the PAD. Whole blood was dropped onto
hydrophilic letters A and B on the PAD, in which the anti-A and anti-B were pre
immobilized, respectively. An absorbent gel pad was used to adsorb excess blood
sample and washing solution during the washing step. The particle size of
agglutinated red blood cells (RBCs) could not be eluted out of the paper by the
elution solution. In contrast, non-agglutinated RBCs were washed out by means of
elution solution. The devices could be used for real blood samples in a wide
range of hematocrit levels, 21-59%. Unknown blood group samples (n = 500) were
identified by the developed device and the results were compared with the
conventional method, revealing 100% accuracy. Because of its compact size with
low-cost fabrication, the portable ABO blood typing device has great potential
for point-of-care testing, particularly in developing countries.
PMID- 29953330
TI - NMR spectroscopic characterization of a model RNA duplex reflecting the core
sequence of hammerhead ribozymes.
AB - Hammerhead ribozymes are a model system for studying molecular mechanism of RNA
catalysis. Physicochemical data-driven mechanistic studies are an indispensable
step towards understanding the catalysis of hammerhead ribozymes. Here we
characterized a model RNA duplex with catalytically important sheared-type G12-A9
base pair and A9-G10.1 metal ion-binding motif in hammerhead ribozymes. By using
high magnetic field NMR, all base proton signals, including catalytic residues,
were unambiguously assigned. We further characterized structural features of this
RNA molecule and found that it reflects the structural features of the A9-G10.1
motif of hammerhead ribozymes. Therefore, this RNA molecule is suitable for
extracting an intrinsic physicochemical properties of catalytically important
residues.
PMID- 29953331
TI - rehabilitation engineers, technologists, and technicians: vital members of the
assistive technology team.
AB - The purpose of this white paper is to describe the rehabilitation engineering
professions, specifically rehabilitation engineers, rehabilitation
technologists/assistive technologists, and rehabilitation technicians. An ad-hoc
committee was convened by the Rehabilitation Engineering and Technologists (RE&T)
Professional Standards Group (PSG) at the 2013 annual meeting, RESNA Conference
in Seattle, Washington. The ad-hoc committee consists of rehabilitation
engineering professionals who have experience working in a variety of
environments, and with a multitude of professionals. Since the initiation of the
ad-hoc committee, versions of this document were published in the Proceedings of
the 2014 RESNA Conference and the 2015 RESNA Conference, and feedback has been
incorporated into the document from external stakeholders. Furthermore, the white
paper was published on the RESNA Website in August of 2015 for public comment.
This white paper is the synthesis of the work from the ad-hoc committee, as well
as the feedback obtained at the two conference presentations, the public comment
period and a review by the RESNA Board of Directors. The white paper is not meant
as a systematic review of the literature, nor a formal research process. However,
the literature, including gray literature, and expert opinion heavily influenced
the development of the white paper.The ad-hoc committee reviewed over 80
different sources in preparing the white paper (see Appendix). The white paper
defines the role of rehabilitation engineering professionals based on
descriptions found in the literature, and historical experience of stakeholders.
Furthermore, it describes the role of rehabilitation engineering professionals in
numerous work settings, and describes current and future education and training
opportunities. Finally, the white paper provides multiple case studies on the
role of rehabilitation engineering professionals in a transdisciplinary assistive
technology service delivery process. The white paper is meant as a guide to
describe the typical rehabilitation engineering professions in their most generic
forms. While there will be exceptions to the rule, the consensus accumulated in
this paper and the iterative methods used to aggregate the content, states a
majority perspective of current rehabilitation engineering professionals. This
document provides a framework for future discussions on the advancement of
rehabilitation engineering with the goal of improving the quality of life of
individuals with disabilities through the application of science and technology.
PMID- 29953333
TI - A Secreted 'Candidatus Liberibacter asiaticus' Peroxiredoxin Simultaneously
Suppresses Both Localized and Systemic Innate Immune Responses In Planta.
AB - The oxidative (H2O2) burst is a seminal feature of the basal plant defense
response to attempted pathogen invasions. In 'Candidatus Liberibacter asiaticus'
UF506, expression of the SC2 prophage-encoded secreted peroxidase (F489_gp15)
increases bacterial fitness and delays symptom progression in citrus. Two
chromosomal 1-Cys peroxiredoxin genes, CLIBASIA_RS00940 (Lasprx5) and
CLIBASIA_RS00445 (Lasbcp), are conserved among all sequenced 'Ca. L. asiaticus'
strains, including those lacking prophages. Both LasBCP and LasdPrx5 have only a
single conserved peroxidatic Cys (CP/SH) and lack the resolving Cys (CR/SH).
Lasprx5 appeared to be a housekeeping gene with similar moderate transcript
abundance in both 'Ca. L. asiaticus'-infected psyllids and citrus. By contrast,
Lasbcp was expressed only in planta, similar to the expression of the SC2
peroxidase. Since 'Ca. L. asiaticus' is uncultured, Lasbcp and Lasprx5 were
functionally validated in a cultured surrogate species, Liberibacter crescens,
and both genes significantly increased oxidative stress tolerance and cell
viability in culture. LasBCP was nonclassically secreted and, in L. crescens,
conferred 214-fold more resistance to tert-butyl hydroperoxide (tBOOH) than wild
type. Transient overexpression of Lasbcp in tobacco suppressed H2O2-mediated
transcriptional activation of RbohB, the key gatekeeper of the systemic plant
defense signaling cascade. Lasbcp expression did not interfere with the
perception of 'Ca. L. asiaticus' flagellin (flg22Las) but interrupted the
downstream activation of RbohB and stereotypical deposition of callose in
tobacco. Critically, LasBCP also protected against tBOOH-induced peroxidative
degradation of lipid membranes in planta, preventing subsequent accumulation of
antimicrobial oxylipins that can also trigger the localized hypersensitive cell
death response.
PMID- 29953332
TI - Learning Efficiency: Identifying Individual Differences in Learning Rate and
Retention in Healthy Adults.
AB - People differ in how quickly they learn information and how long they remember
it, yet individual differences in learning abilities within healthy adults have
been relatively neglected. In two studies, we examined the relation between
learning rate and subsequent retention using a new foreign-language paired
associates task (the learning-efficiency task), which was designed to eliminate
ceiling effects that often accompany standardized tests of learning and memory in
healthy adults. A key finding was that quicker learners were also more durable
learners (i.e., exhibited better retention across a delay), despite studying the
material for less time. Additionally, measures of learning and memory from this
task were reliable in Study 1 ( N = 281) across 30 hr and Study 2 ( N = 92;
follow-up n = 46) across 3 years. We conclude that people vary in how efficiently
they learn, and we describe a reliable and valid method for assessing learning
efficiency within healthy adults.
PMID- 29953334
TI - Center Rot of Onion (Allium cepa) Caused by Pantoea ananatis Requires pepM, a
Predicted Phosphonate-Related Gene.
AB - Pantoea ananatis, a cause of center rot of onion, is problematic in the United
States and elsewhere. The bacterium lacks disease determinants common to most
other bacterial pathogens of plants. A genomic island containing the gene pepM
was detected within many onion-pathogenic strains of P. ananatis of diverse
origins. The pepM gene of P. ananatis putatively encodes a protein that converts
phosphoenolpyruvate to phosphonopyruvate, the first step in the biosynthesis of
phosphonates and related molecules. This gene appears to be essential for center
rot disease. Deletion of pepM rendered the mutant strain unable to cause lesions
in leaves of growing onions and water-soaking of inoculated yellow onion bulbs.
Furthermore, growth of the deletion mutant in onion leaves was significantly
diminished compared with wild-type bacteria, and the mutant failed to cause cell
death in tobacco. Complementation of the mutated strain with pepM restored the
phenotype to wild-type capability. The pepM gene is the first pathogenicity
factor identified that affects bacterial fitness as well as symptom development
in both leaves and bulbs in a pathogen causing center rot of onion.
PMID- 29953336
TI - Color Repair of a Composite Resin Restoration.
AB - Fractured teeth with both enamel and dentin involvement might be treated with
adhesive composite resin restorations. In cases where a perfect color match
between the composite restoration and the remaining tooth structure is not
achieved, a repair might be carried out to correct the color of restoration. This
procedure avoids the restoration replacement, preserving tooth structure without
compromising the esthetic outcome.
PMID- 29953335
TI - Alcohol Use and Experiences of Partner Violence Among Female Sex Workers in
Coastal Andhra Pradesh, India.
AB - This cross-sectional study describes the prevalence and context of violence by
sexual partners against female sex workers (FSWs, N = 589) in Andhra Pradesh and
its association with alcohol use by FSWs and abusive partners. In all, 84% of
FSWs reported alcohol use; 65% reported lifetime physical abuse by a sexual
partner. Most abused women suffered abuse from multiple partners, often triggered
by inebriation or FSW's defiance. In multivariate logistic regressions, frequency
of FSW's alcohol use was associated with abuse by clients and primary partner,
whereas partner's alcohol use was only significant for abuse by primary partner,
not clients.
PMID- 29953337
TI - Application of Calcium Silicate Materials After Acid Etching May Preserve Resin
Dentin Bonds.
AB - INTRODUCTION: The aim of the present study was to evaluate the effect of the
application of calcium silicate materials (CSMs), after acid etching, on the
longevity of the hybrid layer and marginal adaptation of composite restorations.
METHODS AND MATERIALS: Eighty human permanent molars received an intrapulpal
pressure of 15 cm H2O. Sixty teeth received a mesial proximal slot preparation
with the gingival margin extending 1 mm below the cemento-enamel junction. The
samples were divided into two groups. Group 1 received restorations using two
types of etch-and-rinse adhesives: ethanol based (Single Bond, 3M ESPE, St Paul,
MN, USA) and acetone based (Prime & Bond NT, Dentsply, DeTrey GmbH, Germany). In
group 2 samples, a commercially available CSM (ProRoot MTA) was allowed to set
before grinding and placing into a distilled water solution. This solution was
applied on the cavity floor after acid etching. The surface was washed after 30
seconds followed by application of adhesives and restorations as in group 1. The
samples were stored in phosphate-buffered saline for six months, maintaining the
intrapulpal pressure. An epoxy replica was made, and the marginal adaptation was
evaluated using scanning electron microscopy. The percentage of continuous margin
(CM) was recorded for each group. Another 20 samples were used for hybrid layer
evaluation. The crowns were ground to expose dentin. Intrapulpal pressure was
applied. The samples were divided into two groups and restored similar to samples
restored for marginal adaptation evaluation. The samples were longitudinally cut
in 1-mm slices. The slices were stored under 15 cm of phosphate-buffered saline
to simulate the pulpal pressure. After six months, the adhesive interface was
evaluated using a scanning electron microscope. Statistical analysis was done
with two-way analysis of variance with Holm-Sidak's correction for multiple
comparisons. RESULTS: Application of CSMs improved the marginal adaptation values
in both adhesive groups. In group 1, there were areas of incomplete penetration
of resins along with evidence of partial degradation of resin tags. Samples
receiving CSM application after acid etching demonstrated long and regular resin
tags with very few signs of degradation. CONCLUSIONS: Application of CSMs after
acid etching can be a potential avenue in preserving the resin-dentin bonds.
PMID- 29953338
TI - In Vitro Effect of Innovative Desensitizing Agents on Dentin Tubule Occlusion and
Erosive Wear.
AB - PURPOSE: The purpose of this study was to evaluate the effects of four in-office
desensitizing products on dentin tubule occlusion and erosive wear. METHODS:
Dentin hypersensitivity was simulated by EDTA application for five minutes. The
specimens were randomly allocated into five groups (n=11), according to
treatment: No treatment - Control (C), Duraphat (DUR), Desensibilize Nano P (NP),
ClinPro XT Varnish (XTV), and ClinPro White Varnish (CWV). They were then
submitted to erosive/abrasive cycling for five days. After EDTA, treatment, and
cycling, the specimens were analyzed with an environmental scanning electron
microscope (ESEM) to verify the number of opened dentin tubules (ODT) which were
counted by using ImageJ software, and with a profilometer to determine the
surface curvature/loss. ESEM data were analyzed with two-way repeated measure
analysis of variance and Tukey tests. For the profilometer, data were analyzed
with Kruskal-Wallis, Tukey, and Mann-Whitney tests. RESULTS: After treatment, all
groups showed lower ODT than the control, without significant differences between
them. After cycling, the only group that showed lower ODT than the control was
group XTV; however, it did not significantly differ from the other groups. For
the profilometric analysis, there were significant differences in SL between the
experimental times after treatment and after cycling for all groups ( p<0.05).
After cycling, no surface loss was detected in groups DUR and XTV, which
presented a significantly different curvature than group NP and the control
group, but not from group CWV. Surface loss was detected for the control and
groups NP and CWV, without difference among them. CONCLUSION: All desensitizing
agents tested presented promising results concerning the obliteration of dentin
tubules immediately after treatment. XTV was the only desensitizer capable of
preventing the reopening of the tubules after the erosive/abrasive challenges.
XTV and DUR presented a protective effect against dentin erosive wear.
PMID- 29953339
TI - Effect of Thickness on Light Transmission and Vickers Hardness of Five Bulk-fill
Resin-based Composites Using Polywave and Single-peak Light-emitting Diode Curing
Lights.
AB - OBJECTIVES: This study compared light transmission through different thicknesses
of bulk-fill resin-based composites (RBCs) using a polywave and a single-peak
light-emitting diode light-curing unit (LCU). The effect on the surface hardness
was also evaluated. METHODS: Five bulk-fill RBCs were tested. Specimens (n=5) of
1-, 2-, 4-, or 6-mm thickness were photopolymerized for 10 seconds from the top
using a polywave (Bluephase Style) or single-peak (Elipar S10) LCU, while a
spectrophotometer monitored in real time the transmitted irradiance and radiant
exposure reaching the bottom of the specimen. After 24 hours of storage in
distilled water at 37 degrees C, the Vickers microhardness (VH) was measured at
top and bottom. Results were analyzed using multiple-way analysis of variance,
Tukey post hoc tests, and multivariate analysis (alpha=0.05). RESULTS: The choice
of LCU had no significant effect on the total amount of light transmitted through
the five bulk-fill RBCs at each thickness. There was a significant decrease in
the amount of light transmitted as the thickness increased for all RBCs tested
with both LCUs ( p<0.001). Effect of LCU on VH was minimal (etap2=0.010). The 1-,
2-, and 4-mm-thick specimens of SDR, X-tra Fill, and Filtek Bulk Restorative
achieved a VHbottom/top ratio of approximately 80% when either LCU was used.
CONCLUSIONS: The total amount of light transmitted through the five bulk-fill
RBCs was similar at the different thicknesses using either LCU. The polywave LCU
used in this study did not enhance the polymerization of the tested bulk-fill
RBCs when compared with the single-peak LCU.
PMID- 29953340
TI - Effect of Remineralizing Gels on Microhardness, Color and Wear Susceptibility of
Bleached Enamel.
AB - OBJECTIVES: To evaluate the effect of a remineralizing gel combining fluoride and
calcium silicate/phosphate or a sodium fluoride gel on bleached enamel
microhardness, color, and wear susceptibility. METHODS AND MATERIALS: Two hundred
forty bovine enamel-dentin samples were prepared. Baseline analysis of Knoop
microhardness, color coordinates (L*a*b*), and surface profile were performed.
According to the baseline microhardness values, specimens were stratified into
six groups (n=40): NC (negative control)-no treatment; BL (positive control)
bleaching with 40% hydrogen peroxide gel (Opalescence Boost, Ultradent); BL/Rs
bleaching + application of calcium silicate/phosphate gel (Regenerate Serum,
Unilever - Rs); Rs/BL-Rs + bleaching; Rs/BL/Rs-Rs + bleaching + Rs; and BL/F
bleaching + 2% sodium fluoride gel. After the treatment described for each group,
color change (DeltaE) and microhardness were evaluated again. To evaluate
abrasion susceptibility, samples were randomly divided into two subgroups,
according to the toothpaste used (Cp-Close Up or Rt-Regenerate), and underwent
100,000 brushing strokes. The profile of each sample was evaluated and the mean
wear calculated. The data were analyzed by ANOVA and Tukey tests. RESULTS: All
bleached groups showed a significant reduction of microhardness in relation to
the negative control. The groups treated with remineralizing gels showed a
significantly higher microhardness and less wear than the positive control,
although nonsignificant differences were observed among them. Nonsignificant
differences in DeltaE were found among bleached groups. The groups brushed with
Regenerate toothpaste showed significantly less wear than those brushed with
Close Up toothpaste. CONCLUSIONS: The remineralizing gels did not interfere with
bleaching efficacy. However, all the treatments minimized the surface hardness
reduction caused by the bleaching procedure and enamel loss after abrasion.
Regenerate toothpaste resulted in less enamel abrasion.
PMID- 29953341
TI - Effect of Mouth Rinse Treatments on Bleached Enamel Properties, Surface
Morphology, and Tooth Color.
AB - OBJECTIVE: To evaluate, in vitro, the effect of mouth rinse exposure on bleached
enamel. METHODS: Enamel/dentin bovine blocks (4*4*2 mm) were bleached with 35%
hydrogen peroxide (HP) and were submitted to immersion twice daily for 14 days
with different rinses (n=10), including those involving: distilled water (C
[control]), 225-ppm NaF (FM, Colgate Plax Classic), essential oil (EM, Listerine
Tartar Control), 1.5% hydrogen peroxide (HPM, Colgate Plax Whitening), and 2%
hydrogen peroxide, pyrophosphates, and 225-ppm NaF (HPM+P, Colgate(r) Luminous
White). The specimens were stored in a remineralizing solution during all
experiments. Analyses of color (DeltaE, L*, a*, b*) and roughness (Ra) were
performed at the baseline, after HP, and after exposure to the rinse. The cross
sectional microhardness (CSMH) and images by scanning electron microscopy (SEM)
were assessed at the end. The data were subjected to analysis of variance (ANOVA)
(DeltaE), repeated measures ANOVA (Ra), and split-plot ANOVA (CSMH), followed by
the Tukey test. The L*, a*, and b* values were analyzed by generalized linear
models (alpha=0.05). RESULTS: Color changes were not statistically different in
the groups. Ra increased in all groups after bleaching; however, it was
reestablished in C, FM, and HPM+F and increased in EM after 14 days of the rinse.
EM and HPM reduced the CSMH values differing from C and promoted alterations on
the enamel surface visualized by SEM. CONCLUSION: The mouth rinses did not affect
the whitening efficacy or promote benefits on bleached enamel properties.
Moreover, the 1.5% hydrogen peroxide- or essential oil-based mouth rinses
affected the bleached enamel properties, promoting an alteration in morphologic
surface and mineral loss in depth.
PMID- 29953342
TI - Linear Coefficient of Thermal Expansion Evaluation of Glass Ionomer and Resin
Modified Glass Ionomer Restorative Materials.
AB - OBJECTIVE: The purpose of this evaluation was to evaluate the linear coefficient
of thermal expansion (LCTE) of 12 conventional glass ionomer (GIC) and four resin
modified glass ionomer (RMGI) restorative materials. METHODS: GIC and RMGI
specimens (2 mm * 5 mm * 5 mm) were fabricated (n=12) following manufacturer
instructions and were placed in 0.2M phosphate-buffered saline and stored at 37
degrees C and 98% humidity for one week. Specimens had LCTE determined with a
thermomechanical analysis (TMA) unit using a 15 degrees C-50 degrees C heating
cycle as well as a 50 degrees C-15 degrees C cooling cycle at a 5 degrees C/min
rate, using a 3-mm ball-point probe under 0.02 N probe pressure with all
specimens kept saturated with PBS using a specially designed quartz container.
Each specimen was tested three times, with the mean representing the specimen
LCTE. Mean results between specimen heating and cooling were compared with paired
Wilcoxon sign rank test, while results between materials were compared with
Kruskal-Wallis/Dunn's ( alpha=0.05). RESULTS: GIC LCTE ranged from approximately
5 degrees C to 20 degrees C ppm degrees K-1, while the RMGI LCTE ranged from
approximately 25 degrees C to 47 degrees C ppm degrees K-1. With some exception,
the LCTE during cooling displayed a greater trend. SIGNIFICANCE: Under moisture
conditions similar to the oral cavity, GIC materials overall had LCTE values
closer to that reported for tooth structure. RMGI materials displayed higher
values, which was thought to be related to the amount of resin in the matrix. A
generally greater LCTE trend with cooling for all materials was noted, but the
small magnitude of the difference is presently thought to be of minor clinical
significance.
PMID- 29953343
TI - Surface Roughness of Ceramic-Resin Composites After Femtosecond Laser
Irradiation, Sandblasting or Acid Etching and Their Bond Strength With and
Without Silanization to a Resin Cement.
AB - OBJECTIVES: The aim of this study was to investigate the effects of femtosecond
laser irradiation, sandblasting, or acid etching treatments on the surface
roughness of ceramic-resin composites and also shear bond strength (SBS) with and
without silanization to a resin cement. METHODS: Samples of Vita Enamic (VE; Vita
Zahnfabrik, Bad Sackingen, Germany) and Lava Ultimate (LU; 3M ESPE, Seefeld,
Germany) were classified into control (no treatment), sandblasting, hydrofluoric
acid, and femtosecond laser groups (n=30). Surface roughness was determined using
two-dimensional contact profilometry. Surface topography was evaluated using a
three-dimensional contact profilometer and a scanning electron microscope. Then
groups were divided into two subgroups with similar surface roughness values,
including control (C), control + silane (C-S), sandblasting (SB), sandblasting +
silane (SB-S), hydrofluoric acid (HF), hydrofluoric acid + silane (HF-S),
femtosecond laser (FS), and femtosecond laser + silane (FS-S) groups (n=15).
Panavia F 2.0 resin cement was applied to the sample surfaces using an SDI SBS
rig (SDI Limited, Bayswater, Australia). The SBS test was performed after water
storage (24 h, 37 degrees C) and thermocycles (2000 cycles, 5 degrees C to 55
degrees C), and failure modes were evaluated. RESULTS: The highest surface
roughness was observed in the FS group, and the highest SBS was observed in the
FS-S group for both VE and LU ( p<0.001). Silanization improved the SBS of VE
significantly ( p<0.001) in all surface treatments but did not improve that of LU
except in the FS group ( p=0.004). There was a significantly moderate negative
correlation in the VE/SB group ( p=0.012) and a moderate positive correlation in
the VE/HF group ( p=0.049). CONCLUSIONS: Femtosecond laser irradiation was found
to be more effective than sandblasting or acid etching in increasing the surface
roughness, and it was also the most effective surface treatment with silanization
on the SBS of a resin cement to the ceramic-resin composites.
PMID- 29953344
TI - A beginner's guide to rigor and reproducibility in fluorescence imaging
experiments.
AB - Fluorescence light microscopy is an indispensable approach for the investigation
of cell biological mechanisms. With the development of cutting-edge tools such as
genetically encoded fluorescent proteins and superresolution methods, light
microscopy is more powerful than ever at providing insight into a broad range of
phenomena, from bacterial fission to cancer metastasis. However, as with all
experimental approaches, care must be taken to ensure reliable and reproducible
data collection, analysis, and reporting. Each step of every imaging experiment,
from design to execution to communication to data management, should be
critically assessed for bias, rigor, and reproducibility. This Perspective
provides a basic "best practices" guide for designing and executing fluorescence
imaging experiments, with the goal of introducing researchers to concepts that
will help empower them to acquire images with rigor.
PMID- 29953345
TI - Genetically encoded lipid biosensors.
AB - Lipids convey both structural and functional properties to eukaryotic membranes.
Understanding the basic lipid composition and the dynamics of these important
molecules, in the context of cellular membranes, can shed light on signaling,
metabolism, trafficking, and even membrane identity. The development of
genetically encoded lipid biosensors has allowed for the visualization of
specific lipids inside individual, living cells. However, a number of caveats and
considerations have emerged with the overexpression of these biosensors. In this
Technical Perspective, we provide a current list of available genetically encoded
lipid biosensors, together with criteria that determine their veracity. We also
provide some suggestions for the optimal utilization of these biosensors when
both designing experiments and interpreting results.
PMID- 29953346
TI - Monte Carlo Simulation of the Oxygen Effect in DNA Damage Induction by Ionizing
Radiation.
AB - DNA damage induced by ionizing radiation exposure is enhanced in the presence of
oxygen (the "oxygen effect"). Despite its practical importance in radiotherapy,
the oxygen effect has largely been excluded from models that predict DNA damage
from radiation tracks. A Monte Carlo-based algorithm was developed in MATLAB
software to predict DNA damage from physical and chemical tracks through a cell
nucleus simulated in Geant4-DNA, taking into account the effects of cellular
oxygenation (pO2) on DNA radical chemistry processes. An initial spatial
distribution of DNA base and sugar radicals was determined by spatially
clustering direct events (that deposited at least 10.79 eV) and hydroxyl radical
(*OH) interactions. The oxygen effect was modeled by increasing the efficiency
with which sugar radicals from direct-type effects were converted to strand
breaks from 0.6 to 1, the efficiency with which sugar radicals from the indirect
effect were converted to strand breaks from 0.28 to 1 and the efficiency of base
to-sugar radical transfer from *OH-mediated base radicals from 0 to 0.03 with
increasing pO2 from 0 to 760 mmHg. The DNA damage induction algorithm was applied
to tracks from electrons, protons and alphas with LET values from 0.2 to 150
keV/MUm under different pO2 conditions. The oxygen enhancement ratio for double
strand break induction was 3.0 for low-LET radiation up to approximately 15
keV/MUm, after which it gradually decreased to a value of 1.3 at 150 keV/MUm.
These values were consistent with a range of experimental data published in the
literature. The DNA damage yields were verified using experimental data in the
literature and results from other theoretical models. The spatial clustering
approach developed in this work has low memory requirements and may be suitable
for particle tracking simulations with a large number of cells.
PMID- 29953347
TI - Current Perspectives on Novel Drug Carrier Systems and Therapies for Management
of Pancreatic Cancer: An Updated Inclusive Review.
AB - Pancreatic cancer (PC) is one of the most fatal solid tumors, resulting in more
than 250,000 deaths per year globally. It is the eighth leading cause of death
from cancer in men and women throughout the world and is now third leading cause
of cancer-related deaths in the United States. In addition, the worldwide
occurrence of PC ranges from 1 to 10 cases per 100,000 people, indicating a
higher incidence in developed countries. Most patients with locally advanced or
metastatic disease are not candidates for curative resection due to enormously
poor prognosis. Substantial efforts have been taken during the past decade to
distinguish better treatments in the absence of efficient screening methods.
Regardless of wide-ranging efforts, various systems and therapies have shown
insufficient efficacy for PC patients. Therefore, the development of novel drug
delivery systems, strategies, and diverse therapeutic approaches to improve the
range of active molecules for the treatment of PC is critical. Currently, cancer
research focuses on improving the treatment of PC via diverse novel drug delivery
systems of chemotherapeutic agents. These novel drug delivery systems consist of
nanoparticles and liposomes. Strategies or therapeutic approaches intended for PC
include radiation therapy, ablation therapy, and gene therapy. These systems and
approaches can carry the drug molecules to targeted cancer cells to enhance the
effectiveness of tumor penetration. The present review encloses existing novel
drug carrier systems and approaches for PC management.
PMID- 29953348
TI - Lanostane-Type Triterpenes and Abietane-Type Diterpene from the Sclerotia of
Chaga Medicinal Mushroom, Inonotus obliquus (Agaricomycetes), and Their
Biological Activities.
AB - Three new lanostane-type triterpenes (compounds 1-3), 1 new abietane-type
diterpene (compound 4), and 10 known compounds (5-14) were isolated from
sclerotia of Inonotus obliquus. Their structures were elucidated through a
combination of spectrometric techniques, including infrared, 1-dimensional, and 2
dimensional nuclear magnetic resonance and high-resolution electrospray mass
spectrometry. In in vitro assays, compounds 2 and 4-12 showed hepatoprotective
effects against D-galactosamine-induced damage in WB-F344 cells, with inhibitory
effects from 35.4% to 83.8%. Compounds 3, 13, and 14 exhibited selective
cytotoxicity against Bel-7402, A-549, or KB cell lines. Compounds 13 and 14
showed inhibitory effects against protein tyrosine kinases, with half-maximal
inhibitory concentrations of 23.8 and 7.4 MUmol/L, respectively.
PMID- 29953349
TI - Phenotypic and Genetic Diversity of the Culinary-Medicinal Winter Mushroom
Flammulina velutipes (Agaricomycetes) in China.
AB - Flammulina velutipes is one of the mushrooms produced most widely in East Asia.
In this study we investigated phenotypic variations of 7 agronomic traits in 37
F. velutipes strains from China, and we analyzed their genetic diversity with 70
simple sequence repeat markers. The Shannon information index and gene diversity
were 0.894 and 0.478, respectively, demonstrating high genetic variation among
the tested strains. Poor genetic variation was found among white strains, in
contrast to yellow ones. Analysis of population structure resolved 2 unambiguous
genetic groups in the tested F. velutipes strains, with little differentiation
between them (FST = 0.016). Yellow cultivars possibly originated from indigenous
wild strains in southwest China. Phenotypic correlations were identified among
the 7 traits. In particular, stipe length (SL) was significantly positively
correlated with yield, indicating that SL could be used as an index for breeding
high-yield strains. The 2 genetic groups, and white strains and yellow ones,
showed significant differences between SL, yield, and the time interval (days)
from mycelial scratch to formation of the first fruiting body. These results
indicate that these 3 traits were stratified by population structure. Detection
of genetic and phenotypic variations would lay the groundwork for further
breeding of elite F. velutipes strains.
PMID- 29953350
TI - Computational Insights into the Molecular Mechanism of the High Immunomodulatory
Activity of LZ-8 Protein Isolated from the Lingzhi or Reishi Medicinal Mushroom
Ganoderma lucidum (Agaricomycetes).
AB - Ling zhi-8 (LZ-8) is the first fungal immunomodulatory protein (FIP) isolated
from the lingzhi or reishi medicinal mushroom, Ganoderma lucidum. LZ-8
effectively induces interleukin 2 expression and secretion by forming a stable
homodimer, and it is regarded as a good candidate to become a new therapeutic
agent and/or functional food supplement. However, the molecular mechanism by
which LZ-8 dimerization influences the regulation of interleukin 2 is not clear.
In this study we performed structure-based multiple alignment of LZ-8 and an FIP
from Volvariella volvacea, compared the electrostatic potential of their protein
surfaces, and developed a model summarizing the unique electrostatic interaction
in LZ-8 dimerization. In addition, further electrostatic potential and virtual
amino acid mutation analyses suggested that L10, W12, and D45 are the key amino
acid residues responsible for the protein's high immunomodulatory activity. These
findings may provide useful insights into the design and construction of a new
FIP mutant for use in treating and preventing autoimmune diseases.
PMID- 29953351
TI - Antioxidant Properties of the Artist's Conk Medicinal Mushroom, Ganoderma
applanatum (Agaricomycetes), upon Cultivation with para-Substituted Phenolic
Compounds and Tea Leaf Extracts.
AB - In this study we elucidate antioxidative properties of the mushroom Ganoderma
applanatum (Pers.) Pat. enhanced by submerged culture with para-hydroxyphenolic
compounds and tea leaf extracts. The tea extract has been shown to increase to
different extents the antioxidative efficiency of para-substituted phenolics,
with the most profound effect for 2-(4-hydroxyphenyl)ethane-1-ol (tyrosol).
Within the range of physiological concentrations, the symbatic correlation of the
antioxidative action of the fungal samples with the volume of tea extract in the
submerged culture medium was observed. We propose an approach to obtain, through
the use of black tea extracts as the nutrient medium component, large amounts of
G. applanatum seeding mycelia; the extract exerts a profound positive effect on
the level of phenolic-type antioxidants.
PMID- 29953352
TI - Genetic Variability of the Medicinal Tinder Bracket Polypore, Fomes fomentarius
(Agaricomycetes), from the Asian Part of Russia.
AB - We analyzed intraspecies genetic variability of the medicinal tinder bracket
polypore, Fomes fomentarius, from the Asian part of Russia, including the Ural,
Altai, Western Sayan, and Baikal regions. We used nuclear ribosomal DNA internal
transcribed spacer (ITS) sequence data as a standard marker for fungal DNA
barcoding. In the Asian part of Russia, lineage A occurs as sublineage A2, which
differs from sublineage A1 by a single nucleotide insertion at ITS2.3. Sublineage
A2 is distributed up to Lake Baikal in the Ural, Altai, and Western Sayan
regions. It can be characterized as a Eurasian sublineage of F. fomentarius.
Lineage B is also represented by 2 sublineages (B1 and B2), which differ from
each other by nucleotide sequences at ITS2.1. Sublineage B1 is represented by a
small group of isolates from Asia (Iran, China, Nepal, South Korea), whereas
sublineage B2 mainly includes isolates from Europe (Great Britain, Italy, Latvia,
Slovakia, Slovenia) and 2 separate samples from Asia (Iran, China); these locales
compose the distribution area of F. fomentarius. In the Asian part of Russia,
lineage B is represented by sublineage B2 found in the Southern Urals (at the
border between Europe and Asia), which is the only area where sublineages A2 and
B2 are present. These sublineages are characterized by different substrate
spectra: sublineage A2 is predominantly associated with Betula spp. and rarely
with Alnus and Larix trees, whereas sublineage B2 does not have a pronounced
substrate preference and is found in basidiomes collected from Acer, Duschekia,
Prunus, and Salix trees, but not Betula trees. In general, the spectrum of
substrates for F. fomentarius lineages A and B in the Asian part of Russia
corresponds to that in other parts of this polypore's distribution area. Data are
needed on genetic intraspecies variability (polymorphism) in relation to
pharmacological properties for further biotechnological cultivation and use of
the medicinal fungus F. fomentarius.
PMID- 29953353
TI - Determination of Antioxidant Potential of Selected Wild Edible Mushrooms from
India in a Saccharomyces cerevisiae Model System.
AB - Wild edible mushrooms are one of the most fascinating nutraceuticals because of
their pleasant texture, peculiar aroma, and tremendous therapeutic potential;
they have been used since ancient times. In this study we evaluated the
antioxidant potential of 4 wild edible mushrooms-Cantharellus tropicalis, C.
cibarius, Lentinus edodes, and Russula delica-collected from Mizoram, India. We
performed in vitro and in vivo studies using a Saccharomyces cerevisiae stress
response mechanism as the model system. Among the 4 mushrooms, C. cibarius
exhibited the most significant antioxidant activity both in vitro and in vivo,
followed by L. edodes, R. delica, and C. tropicalis. Gas chromatography-mass
spectrometry analysis of methanolic extracts of the mushrooms revealed the
presence of substantial amounts of fatty acids, fatty acid esters, and other
bioactive constituents. The in vitro antioxidant activity was corroborated by in
vivo studies using an S. cerevisiae oxidative stress response mechanism. In spot
assays, the C. cibarius methanolic extract showed the highest scavenging
potential in wild and mutant (sodlDelta and tsalDelta) strains of S. cerevisiae.
These results were confirmed further by determining the level of reactive oxygen
species through the use of fluorescent microscopy and intensity studies. The
results suggested the efficacy of wild edible mushrooms as prominent therapeutic
agents and that they have tremendous nutraceutical properties.
PMID- 29953354
TI - Antioxidant and Hepatoprotective Activities of Crude Polysaccharide Extracts from
Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), by
Ultrasonic-Circulating Extraction.
AB - We recently proposed, and successfully applied, a novel and efficient technique
ultrasonic-circulating extraction (UCE) integrating superfine pulverization-to
extract and prepare antioxidant crude polysaccharides other natural active
substances from Ganoderma lucidum. The aim of this study was to evaluate the
antioxidant and hepatoprotective activities and active ingredients in the powder
from UCE (UCEP) through comparison with powder from hot water extraction (HWEP).
The DPPH radical, ABTS radical, superoxide anion, total antioxidant activity, and
ferric-reducing antioxidant power assay results showed that the UCEP exhibited
stronger (P < 0.01) in vitro antioxidant activity than the HWEP. The
hepatoprotective activity of the extracts was evaluated against CCl4-induced
oxidative damage in the liver. Measurements of reduced glutathione, superoxide
dismutase, and malondialdehyde in rat liver; measurements of alanine
transaminase, aspartate transaminase, and lactate dehydrogenase in rat blood; and
Western blotting for antioxidant proteins of transforming growth factor-beta1,
heme-oxygenase 1, and glutathione per-oxidase showed that the UCEP had
antioxidant activity in vivo either similar to or slightly stronger than (P <
0.1) the HWEP. Further analysis of the active ingredients revealed that the UCEP
and HWEP have similar mean yield and total triterpenoid content, but the former
has significantly higher (P < 0.05) mean yield and total polysaccharide content
than the latter. Our results suggest that the UCEP displays stronger antioxidant
activities because of the larger amount of total polysaccharides; the UCEP may be
able to be used as an antioxidant and liver protectant.
PMID- 29953355
TI - Antioxidant Activity and Infrared Spectroscopy Analysis of Alcoholic Extracts
Obtained from Paecilomyces hepiali (Ascomycetes).
AB - This research studies the influence of substrate on the antioxidant activity of
alcohol extracts of Paecilomyces hepiali. We used corn, rice, millet, and peas as
substrates. Antioxidant activity was measured with the DPPH radical scavenging
method. Concentrations of extracts (6.25, 3.12, 1.56, 0.78, and 0.39 mg/mL) were
applied in all evaluations. Overall antioxidant activity was expressed as the
concentration of substrate that decreased DPPH radical levels by 50% (IC50DPPH)
for 7 methanol and 7 ethanol extracts. A comparison of IC50DPPH allowed us to
conclude that the methanol extracts are more active in scavenging stable DPPH
radicals than are the ethanol extracts. The substrate with antioxidant properties
most suitable for cultivation of P. hepiali was rice supplemented with non
defatted soy flour. The extract most effective in scavenging stable radicals was
the methanol extract of sample 4 (IC50DPPH = 2.33 mg/mL) cultivated on rice with
nondefatted soy flour. The methanol extract of sample 7 cultivated on peas was
less effective (IC50DPPH = 11.50 mg/mL). By crystallizing these extracts, we
managed to obtain sufficient quantities of 6 samples in a solid state, for which
infrared spectra were measured and confirmed the presence of amino acids in the
extracts.
PMID- 29953356
TI - Isolation and Structure Determination of Antiproliferative Secondary Metabolites
from the Potato Earthball Mushroom, Scleroderma bovista (Agaricomycetes).
AB - Mycochemical examination of a methanol extract of Scleroderma bovista Fr.
(Agaricomycetes) led to the isolation of 7 compounds, which were, to our
knowledge, identified for the first time in this species. The chemical structures
of these compounds were determined through extensive spectroscopic methods
(nuclear magnetic resonance and mass spectrometry). The fungal metabolites were
identified as steroids based on ergostane (compounds 1-4) and lanostane
(compounds 6 and 7) skeletons, whereas compound 5 was a ceramide derivative. We
evaluated the antiproliferative activity of compounds 4-7 against human cancer
cell lines (HeLa, A2780, MDA-MB-231, and MCF-7) using the MTT assay. The
lanostane-type derivatives (compounds 6 and 7) and ergosterol peroxide 3
glucoside (compound 4) exerted significant antiproliferative property on 1 or
more human cancer cell lines.
PMID- 29953357
TI - Nephroprotective and Antioxidant Effects of King Tuber Oyster Medicinal Mushroom,
Pleurotus tuber-regium (Agaricomycetes), on Carbon Tetrachloride-Induced
Nephrotoxicity in Male Sprague Dawley Rats.
AB - Chronic kidney disease is a health burden worldwide but particularly in sub
Saharan Africa, with dwindling resources as a result of poor commodity export,
devaluation of currencies, and corruption that had decreased the average family
income and substantially increased the number of persons living on less than
$1.90/day. Natural products are part of the healthcare delivery system in that
part of the world. This study was conducted to evaluate the protective effects of
Pleurotus tuber-regium on the kidneys of rats treated with carbon tetrachloride
(CCl4) for 13 weeks. Sixty rats were divided into 6 groups, with 10 animals in
each group. Group I (control) received olive oil (3 mL/kg) intraperitoneally
twice weekly and were given feed and water ad libitum. Group II received CCl4 (3
mL/kg, 30% in olive oil) twice weekly. Groups III, IV, and V received 100, 200,
and 500 mg/kg wild edible P. tuber-regium (33.3% in feed) daily, respectively, in
addition to 3 mL/kg CCl4 twice weekly. Group VI received 500 mg/kg P. tuber
regium (33.3% in feed) daily. At the end of 13 weeks, the animals were sacrificed
and kidney weights recorded. Serum concentrations of creatinine, urea, and
fasting blood glucose were assayed. Malondialdehyde, ascorbic acid, alpha
tocopherol, superoxide dismutase, catalase, total glutathione, and peroxidase
were measured in kidney homogenate. The kidneys were also histologically
examined. Administration of CCl4 to rats significantly (P < 0.05) increased the
absolute and relative kidney weights from 0.93 +/- 0.04 and 0.38 +/- 0.02 g in
the control group to 1.30 +/- 0.04 and 0.58 +/- 0.02 g in the treated groups
(Groups III, IV, and V), respectively. CCl4 administration increased the
concentrations of creatinine, urea, fasting blood glucose, and malondialdehyde
from 0.53 +/- 0.05 mg/dL, 17.0 +/- 1.10 mg/dL, 72 +/- 2.80 mg/dL, and 1.40 +/-
0.32 MUmol/L in the control group to 0.84 +/- 0.03 mg/dL, 43.0 +/- 6.90 mg/dL, 77
+/- 2.2 mg/dL, and 14.0 +/- 3.5 MUmol/L in the treated groups, respectively. The
concentrations of ascorbic acid, alpha-tocopherol, superoxide dismutase,
catalase, total glutathione, and peroxidase decreased significantly (P < 0.05)
from 0.41 +/- 0.02 mg/dL, 5.15 +/- 0.21 MUg/mL, 8.49 +/- 0.38 units/mL, 75.20 +/-
4.57 mU/mL, 1.62 +/- 0.03 MUg/mL, and 9.74 +/- 0.40 mU/mL in the control group to
0.24 +/- 0.03 mg/dL, 1.80 +/- 0.11 MUg/mL, 2.78 +/- 0.30 units/mL, 31.9 +/- 5.87
mU/mL, 0.36 +/- 0.04 MUg/mL, and 3.84 +/- 0.22 mU/mL in the treated groups,
respectively. Photomicrographs showed that P. tuber-regium prevented the fibrosis
and tubular and Bowman capsule distortions observed in the CCl4-only group. P.
tuber-regium is effective in protecting the kidneys against CCl4-induced damage.
PMID- 29953358
TI - Role of Hydroalcoholic Extract of Lingzhi or Reishi Medicinal Mushroom, Ganoderma
lucidum (Agaricomycetes), in Facilitating Cellular Acclimatization in a Low
Oxygen Microenvironment.
AB - Ganoderma lucidum is known to exert many health benefits including effects to
improve oxygen utilization. Therefore, this study was designed to evaluate the
role of a hydroalcoholic G. lucidum extract in providing tolerance to HT22 cells
grown under hypoxic conditions. HT22 cells were exposed to 0.5% O2 in the
presence or absence of the extract for 24 hours. At the end of the exposure
period, we performed cell viability assays, cell cycle analysis, and biochemical
and protein expression studies. The extract-treated cells revealed less cell
death, minimized caspase 3 and reactive oxygen species levels, and relieved G0/G1
cell cycle arrest compared with hypoxic cells cultured without the extract.
Further, extract-treated cells showed improved expression of Nrf2, heme oxygenase
1, and metallothionein and stabilized levels of hypoxia-inducible factor 1alpha.
Moreover, lower levels of nuclear factor-kappaB and tumor necrosis factor a were
evident in extract-treated cells. Overall, the G. lucidum extract reduced hypoxia
induced cell death and augmented transcription factors (HIF-1alpha and Nrf2),
conferring tolerance to hypoxia.
PMID- 29953359
TI - Traditional Knowledge of Gucchi, Morchella esculenta (Ascomycetes), in Doda
District, Jammu and Kashmir, India.
AB - The gucchi mushroom, Morchella esculenta, commonly known as the morel, is called
thunthoo in the Bhaderwahi dialect spoken in District Doda of Jammu and Kashmir,
India, and is an expensive food item that grows wild and is collected manually.
Its nutritive and medicinal values are acknowledged. The farming community in the
district traditionally collects the mushroom from forested areas through a well
managed community approach. Elders of families and communities have taught
farmers how to identify the mushroom, recognize distribution patterns, and
collect it. The knowledge and ability to differentiate M. esculenta from other
poisonous wild mushrooms has also been inherited from the elders and community
members. Women and children collect it from the outskirts of the forested areas
and villages; men penetrate deeper into the dense forests in groups. It is either
sold fresh to local shopkeepers or dried at home; the majority of gucchi
collectors do the latter. Traditionally, the mushrooms are most commonly dried in
the sun or the kitchen. The mushroom fetches a remunerative price and supplements
the household incomes of the rural folk who collect it. Marketing gucchi has not
been reported as a constraint. It has traditionally been used to overcome gastric
problems and indigestion, as a tonic, to help heal wounds, and to reduce joint
pain. Its medicinal uses are, however, restricted to only the hills and far-flung
areas.
PMID- 29953360
TI - Detection of Quantitative Trait Loci Underlying Yield-Related Traits in Shiitake
Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes).
AB - Increasing yield is a principal goal when breeding Lentinus edodes. The detection
of quantitative trait loci (QTLs) underlying yield and its related traits,
precocity and the number of fruiting bodies (NFs), is important in order to breed
high-yield cultivars. Using composite interval mapping (CIM), we mapped a total
of 25 QTLs responsible for precocity, NFs, and yield in 2 segregating populations
of L. edodes. QTLs for the 3 traits were mapped on 5 different linkage groups,
contributing 5.9% to 15.4% of the phenotypic variation. Colocated QTLs were also
found underlying multiple traits, implying the presence of a genic pleiotropic
effect or tightly linked genes. This is, to our knowledge, the first report of
the genetic dissection of precocity, NFs, and yield using QTL mapping in L.
edodes. Findings of this study will facilitate marker-assisted breeding of high
yield cultivars of L. edodes.
PMID- 29953361
TI - Nutrient and Chemical Analysis of Fruiting Bodies of a Cultivar of the Chinese
Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes).
AB - A cultivar of fruiting bodies of Ophiocordyceps sinensis (FBOS; OCS02) was
analyzed for nutrients, bioactive compounds, and heavy metal content to showcase
its potential as a competitive, sustainable, and safe alternative to wild types
and other cultivars. A previous 28-day subacute toxicity study showed that doses
up to 1 g . kg-1 did not cause any adverse effects in Sprague-Dawley rats. The
OCS02 cultivar contained large amounts of cordycepin, polysaccharides, and
essential and semi-essential amino acids (0.66, 482.80, 99.02, and 101.04 g . kg
1, respectively) compared with levels reported in wild types and in cultivated
mycelia. beta-1,3/1,6-glucan content was considerably high at 342.50 g . kg-1.
The potassium level (5.14 g kg-1) tied in well with the low sodium content (0.121
g . kg-1)-6 times lower than amounts in wild types. We found no detectable levels
of heavy metals such as lead, arsenic, cadmium, and mercury. The major amino
acids found in FBOS (0CS02 cultivar) were arginine, lysine, serine, and threonine
at 45.20, 20.30, 18.60, and 18.20 g . kg-1, respectively. The cultivated FBOS
(OCS02 cultivar) is a comparable alternative to wild-type and other cultivated
strains of O. sinensis. It has potential as a nutraceutical to meet market
demand.
PMID- 29953362
TI - Evaluation of Antibacterial and Anticancer Activities of the Medicinal Fungus
Ophiocordyceps sobolifera (Ascomycetes) from Thailand.
AB - Eleven strains of an entomopathogenic fungus, isolated and identified as
Ophiocordyceps sobolifera, were screened for activity against 5 strains of Gram
negative and 5 strains of Gram-positive bacteria. Four of the isolates, Cod
KK1634, Cod-KK1643, Cod-KS1601, and Cod-SN1626, had activity against the test
strains of Grampositive bacteria. Of these 4 extracts, the Cod-KK1643 extract had
the lowest minimum inhibitory and bactericidal concentrations. The Cod-KK1643
extract exhibited both concentration- and time-dependent bactericidal activity.
Moreover, the Cod-KK1643 extract induced morphological alterations in bacterial
cells, including decreased cell size, a crushed appearance, and cell lysis. It is
surprising to note that the extracts also inhibited MCF-7 cell proliferation,
with a half-maximal inhibitory concentration of 47.09 +/- 33.64 mg/mL after 72
hours. The extracts also inhibited MCF-7 cell migration, with the lowest
percentage of relative closure achieved with Cod-KK1643. These findings represent
what is to our knowledge the first information on the activities of O. sobolifera
mycelial extracts against bacteria and the human breast cancer MCF-7 cell line.
PMID- 29953363
TI - Dietary Supplementation of Lion's Mane Medicinal Mushroom, Hericium erinaceus
(Agaricomycetes), and Spatial Memory in Wild-Type Mice.
AB - Hericium erinaceus is an edible and medicinal mushroom with potential
neuroprotective effects. The study of H. erinaceus has attracted considerable
attention during the past 10 years, particularly with regard to its potential
utility in the treatment of motor dysfunction, Alzheimer disease, and other forms
of dementia. We previously determined that oral supplementation with H. erinaceus
results in significant improvements in novelty-seeking behavior and novel object
recognition in mice. In this study, H. erinaceus was added to the diets of wild
type mice for 2 months, and effects on spatial memory were evaluated by means of
a Y maze and an object location task. We found that H. erinaceus increased
general locomotor activity but had no effect on spatial memory. Thus, oral
supplementation with H. erinaceus yields specific and selective improvements in
recognition memory without altering spatial working memory, which supports the
hypothesis that recognition memory can be modeled as a dual process. In this
model, the perirhinal cortex supports the recognition of individual items as part
of a circuit involved in familiarity with an encountered stimulus, whereas the
hippocampus supports recollected associations and relationships between stimuli.
PMID- 29953364
TI - Conditions Affecting Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum
(Agaricomycetes) Basidiome Quality, Morphogenesis, and Biodegradation of Wood By
products in Argentina.
AB - Solid-state fermentation (SSF) with the medicinal higher Basidiomycete Ganoderma
lucidum was studied as a strategy to use pine (Pinus radiata D. Don) and poplar
(Populus nigra L.) wood chips and sawdust. Fruiting bodies were produced and the
value of the biotransformed substrate was assessed. The highest mushroom yield
(63 g dry weight per kilogram of dry substrate) was obtained with poplar sawdust
and wood chips. Immersion of the bioreactors was a simple watering method that
obtained suitable yields. Two morphological types were induced using 2 different
incandescent light intensities. High light irradiation induced the highest valued
mushroom morphology (as a whole product). Time course study of substrate
biodegradation and mycelial growth dynamics indicated that the trophophase lasted
20 days and presented laccase activity of 0.01-0.03 units . g-1. The activity at
idiophase was 10 times higher. Aqueous and alkali extracts, as well as
carbohydrase enzyme profile activity, revealed differences in the properties of
the residual substrate; some related to the substrate source are considered to be
of concern for further use of this pretreated biomass. In view of the results
obtained, we propose use of SSF of pine and poplar with G. lucidum to profitably
recycle softwood by-products from the timber industry.
PMID- 29953365
TI - DNA Methylation in Radiation-Induced Carcinogenesis: Experimental Evidence and
Clinical Perspectives.
AB - Ionizing radiation is a valuable tool in many spheres of human life. At the same
time, it is a genotoxic agent with a well-established carcinogenic potential.
Progress achieved in the last two decades has demonstrated convincingly that
ionizing radiation can also target the cellular epigenome. Epigenetics is defined
as heritable changes in the expression of genes that are not due to alterations
of DNA sequence but consist of specific covalent modifications of chromatin
components, such as methylation of DNA, histone modifications, and control
performed by non-coding RNAs. Accumulating evidence suggests that DNA
methylation, a key epigenetic mechanism involved in the control of expression of
genetic information, may serve as one of the driving mechanisms of radiation
induced carcinogenesis. Here, we review the literature on the effects of ionizing
radiation on DNA methylation in various biological systems, discuss the role of
DNA methylation in radiation carcinogenesis, and provide our opinion on the
potential utilization of this knowledge in radiation oncology.
PMID- 29953366
TI - Radiation-Induced Cell Death: Signaling and Pharmacological Modulation.
AB - Currently, more than half of newly diagnosed cancer patients receive radiation
treatment. However, the radioresistance of tumor cells as well as the early and
late side effects limit the beneficial outcome of radiotherapy. Accordingly, the
innovative approaches to maximize tumor killing and/or minimize radiation
toxicity remain a major focus of interest. In the past decade, several pieces of
evidence have shown the importance of different modes of regulated cell death
(RCD) in the radioresponse of malignant and normal tissues. Furthermore, the
biological modulation of radiation-induced RCDs has come to attention as a novel
therapeutic means. Here, we review the major signaling pathways that orchestrate
all types of RCD initiated by exposure to ionizing radiation. The latest advances
in the development of small-molecule RCD modulators (both natural and synthetic)
that are intended for widening the therapeutic window of radiotherapy are also
discussed.
PMID- 29953368
TI - Individual Response to Ionizing Radiation and Personalized Radiotherapy.
AB - Radiation therapy remains one of the most effective cancer treatments.
Nevertheless, biology-driven personalized radiation therapy that enables
treatment according to the biological characteristics of the individual tumors
and normal tissues still needs to be implemented in the clinic. Understanding the
mechanisms of radiation response in both tumors and normal tissues is necessary
to develop reliable predictive biomarkers for tumor radioresistance and normal
tissue toxicity as well as to exploit new therapeutic opportunities for tumor
radiosensitization. In this article, we review the mechanisms of tumor
radiosensitivity as well as the early and late responses of normal tissues to
therapeutic radiation exposure. We also discuss the possible implementation of
these mechanisms for biology-driven personalized radiation treatment.
PMID- 29953369
TI - Secondary Malignancies in the Era of High-Precision Radiation Therapy.
AB - Although modern radiation therapy delivers a localized distribution of ionizing
energy that can be used to cure primary cancers for many patients, the inevitable
radiation exposure to non-targeted normal tissue leads to a risk of a radiation
related new cancer. Modern therapies often produce a complex spectrum of
secondary particles, both charged and uncharged, that must be considered both in
their physical radiation transport throughout the patient and their potential to
induce biological damage, which depends on the microscopic energy deposition from
the cascade of primary, secondary, and downstream particles. This work summarizes
the experimental data for relative biological effectiveness for particles
associated with modern radiotherapy in light of their capacity to induce
secondary malignancies in patients. A distinction is highlighted between the
radiobiological experimental data and the coarser metrics used frequently in
radiation protection. For critical assessment of the risks of secondary
malignancies for patients undergoing radiation therapy, a detailed description of
primary and secondary radiation fields is needed, though not routinely considered
for individual patient treatments. Furthermore, not only the particle type, but
also the microscopic dose and track structure, must be considered, which points
to a demand for detailed physics models and high-performance computing strategies
to model the risks.
PMID- 29953370
TI - Radiation-Induced Gliomas.
AB - Radiation therapy has been a cornerstone of cancer management for many decades
and is an integral part of the multi-modality care of patients with brain tumors.
The known serious side effects of radiation therapy on the head or central
nervous system are uncommon and include radiation necrosis, microangiopathy, and
progressive leukencephalopathy. In addition, there have been descriptions of
radiation-induced tumors including sarcomas, gliomas, lymphomas, and carcinomas
of the thyroid. Patients who have received radiation therapy of the head or face
may rarely develop radiation-induced tumors, a majority of which are meningiomas,
followed by radiation-induced gliomas (RIGs) and sarcomas. The increased risk of
RIGs is well described in both the pediatric and adult populations and after the
use of both therapeutic and diagnostic radiations. The incidence of RIGs is
estimated at approximately 0.5-2.7% at a latent period of approximately 15 years.
The risk appears to be dependent on patient age at treatment, as well as
radiation dose and treatment volume considerations. The scope of this review
focuses on the etiology, clinical features, and management of RIGs as they relate
to previous radiation therapy.
PMID- 29953371
TI - Radiation and Brain Tumors: An Overview.
AB - The use of radiation is an essential part of both modern cancer diagnostic
assessment and treatment. Next-generation imaging devices create 3D
visualizations, allowing for better diagnoses and improved planning of precision
treatment. This is particularly important for primary brain cancers such as
diffuse intrinsic pontine glioma or the most common primary brain tumor,
glioblastoma, because radiotherapy is often the only treatment modality that
offers a significant improvement in survival and quality of life. In this review,
we give an overview of the different imaging techniques and the historic role of
radiotherapy and its place in modern cancer therapy. Finally, we discuss three
key areas of risks associated with the use of ionizing radiation: (1) brain tumor
induction mainly as a consequence of the diagnostic use of radiation; (2)
cognitive decline as a consequence of treating childhood brain tumors as an
example of long term consequences often neglected in favor of highlighting
secondary primary cancers; and (3) pro-proliferative and pro-invasive alterations
that occur in tumor cells that survive radiotherapy. Throughout the discussion,
we highlight areas of potential future research.
PMID- 29953372
TI - Problems and Possibilities of Passive Thermoacoustical Tomography.
AB - The problems and possibilities of passive thermoacoustical tomography are
discussed. Algorithms for reconstruction of internal temperature in the human
body are proposed. These algorithms take into account heat transfer and blood
circulation and the absorption factor, obtained previously. The results of
reconstruction of deep temperature in the human hand in simulations with the
medium with a heated object are reported. These results support the possibility
of the correlation measurements of the thermal acoustic radiation. Such
measurements allow the information on ultrasound absorption by the object under
study to be obtained and open the way to the development of a passive acoustic
tomography system using a priori information on the absorption factor.
PMID- 29953373
TI - Fluorescence Spectroscopy Application in the Express-evaluation of the
Gastrointestinal Microflora.
AB - Possible application is studied for fluorescence spectroscopy in the express
evaluation of the gastrointestinal microflora. This diagnostic approach is
feasible because of the difference in fluorescent spectra from different
microorganisms, with anaerobic microorganisms exhibiting the most pronounced
fluorescence. It was found that fluorescence strength raised with an increase in
the bacteria Bacteroides and bifid bacteria, whereas it decreased with an
increase in Escherichia coli. The bacteria Bacteroides and bifid bacteria are the
most typical representatives of anaerobic bacteria, whereas the bacteria
Escherichia coli arc the typical representatives of aerobic bacteria. According
to the literature, Bacteroides and bifid bacteria reveal an intense fluorescence.
Bearing in mind that these genera of bacteria play an important role in the
gastrointestinal microbiocenosis, fluorescence spectroscopy can be used as a
diagnostic means for gastrointestinal dysbacteriosis.
PMID- 29953374
TI - Fundamental Aspects of Electromagnetic Hyperthermia in Medicine.
AB - This article considers the fundamental advantages of electromagnetic hyperthermia
over different techniques for heating the human being's body. It also presents
basic parameters that characterize hyperthermia and electromagnetic techniques
for heating biological tissues. Apart from that, engineering solutions directed
at providing effective hyperthermia are outlined.
PMID- 29953375
TI - Numerical Simulation of Light Propagation and Scattering in Turbid Biological
Media.
AB - This article considers the processes of light propagation and scattering in
biological tissues. The results obtained made it possible to estimate basic
signal parameters and their dependence on various optical parameters with respect
to the laser Doppler flowmeter and laser Doppler microscope. We also developed a
new method to determine the indicatrix asymmetry of single and multiple light
scattering by a suspension of oriented spheroidal particles that simulated
erythrocytes in a shear flow. It was found that the angular dependence of the
asymmetry index provides information on the shape and orientation of particles.
In addition, we obtained single scattering indicatrices, which may improve the
accuracy of computer simulation of light scattering by blood.
PMID- 29953367
TI - Profiles of Radioresistance Mechanisms in Prostate Cancer.
AB - Radiation therapy (RT) is commonly used for the treatment of localized prostate
cancer (PCa). However, cancer cells often develop resistance to radiation through
unknown mechanisms and pose an intractable challenge. Radiation resistance is
highly unpredictable, rendering the treatment less effective in many patients and
frequently causing metastasis and cancer recurrence. Understanding the molecular
events that cause radioresistance in PCa will enable us to develop adjuvant
treatments for enhancing the efficacy of RT. Radioresistant PCa depends on the
elevated DNA repair system and the intracellular levels of reactive oxygen
species (ROS) to proliferate, self-renew, and scavenge anti-cancer regimens,
whereas the elevated heat shock protein 90 (HSP90) and the epithelial-mesenchymal
transition (EMT) enable radioresistant PCa cells to metastasize after exposure to
radiation. The up-regulation of the DNA repairing system, ROS, HSP90, and EMT
effectors has been studied extensively, but not targeted by adjuvant therapy of
radioresistant PCa. Here, we emphasize the effects of ionizing radiation and the
mechanisms driving the emergence of radioresistant PCa. We also address the
markers of radioresistance, the gene signatures for the predictive response to
radiotherapy, and novel therapeutic platforms for targeting radioresistant PCa.
This review provides significant insights into enhancing the current knowledge
and the understanding toward optimization of these markers for the treatment of
radioresistant PCa.
PMID- 29953376
TI - Cardiovascular System's States under Stress: Reviews of Methods.
AB - A comparative analysis is made of various methods for processing
electrocardiograms and RR-interval sequences. This analysis was carried out by
using standard nonlinear-dynamics algorithms and methods. Apart from that, we
assessed the expediency of using a number of characteristics to classify the
cardiovascular system's state under stress.
PMID- 29953377
TI - Study on the Design and Application of Combining Low-Frequency Ultrasound with
Laser Radiation in Surgery and Therapy.
AB - Further development of combined laser-ultrasonic medical technologies is
presented. An analysis is made of the main effects produced by low-frequency
ultrasound on biological tissues. These effects include cavitation, acoustic
streamings, acoustic pressure, and mechanical influence. Possible application of
low-frequency ultrasound is considered in regard to tumor therapy, bactericidal
treatment of infectious tissues, and spray treatment of head and neck wounds.
Some limitations of ultrasound application in medicine are discussed, and the
feasibility of combining laser radiation with ultrasound is studied. A number of
new laser-ultrasonic combinations are put forward and developed. They embrace the
combination of photodynamic therapy with ultrasonic tumor therapy
(sonophotodynamic therapy), laser-ultrasonic wound treatment (spray treatment),
and laser-ultrasonic drug delivery (photophonophoresis). Some of the above
mentioned technologies were tested experimentally, and the results obtained are
considered.
PMID- 29953378
TI - Reviews of Ultrasonic Vibrodrives for Traumatology.
AB - An investigation was made of the dynamics of ultrasonic vibrodrills with a common
source of rotational and ultrasonic reciprocal motions. The source was
constructed on the basis of an electroacoustic transducer of longitudinal
vibrations. The dependences of power, rotation speed, and flutter rates were
plotted for various pushers as a function of biological tissue drag torque. The
results obtained allowed us to determine the optimal parameters of basic
ultrasonic modes used in treating biological tissues. Apart from that, ultrasonic
vibrodrill pilot models, which are new in principle, are presented. They were
designed to be applied in traumatology. A distinguishing feature of these
vibrodrills is that an electroacoustic transducer of longitudinal vibrations is a
source of two motion types: rotational and ultrasonic reciprocal.
PMID- 29953379
TI - Procedures for Evaluating the Adequacy of Anesthesia.
AB - Assessing adequacy of anesthesia requires evaluation of its components: hypnosis,
analgesia, and neuromuscular transmission. In order to do this, many methods have
been developed that process signals representing different modalities. Assessment
of hypnosis requires cortical measures of the central nervous system (CNS);
methods that assess analgesia concentrate on subcortical and spinal levels of the
CNS; and neuromuscular transmission is a peripheral phenomenon. This article
presents an overview of the current state of methods available for measuring each
of these components. We conclude that, whereas important gains have been made in
the area of assessment of hypnosis, mainly owing to the advancement of methods
using EEG and auditory evoked potentials, and whereas neuromuscular transmission
can be objectively monitored using motor nerve stimulation, assessment of
analgesia still contains many challenges.
PMID- 29953380
TI - Reviews of Modeling Techniques for Neuromonitoring Depth of Anesthesia.
AB - This article reviews the various modeling techniques for neuromonitoring depth of
anesthesia (DOA). Traditional techniques such as parametric, predictive, optimal,
and adaptive modeling; proportional, integral, derivative (PID) modeling;
together with modern techniques such as bispectral-based, artificial neural
network-based, fuzzy logic, and neuro-fuzzy modeling, bring us to the current
state of the art in DOA neuromonitoring. This article reviews historical
information about each of the modern techniques and provides an example
demonstrating its implementation; reviews drug pharmacokinetic/pharmacodynamic
(PK/PD) and drug interaction PK/PD modeling techniques for a balanced total
intravenous anesthesia (TIVA) administration; and discusses the existing
technical problems and clinical challenges, suggesting new techniques necessary
for the future development of a DOA monitoring and control system.
PMID- 29953381
TI - Developments in Gastrointestinal Electrical Stimulation.
AB - Electrical stimulation of the gastrointestinal (GI) tract, analogous to pacing
the human heart, is an attractive idea. This is because these organs, like the
heart, have their own natural pacemakers, and the electrical signals they
generate can be altered by externally delivering certain types of electric
currents via intraluminal or serosal electrodes to certain areas of the GI tract.
A number of studies on animals have been accomplished successfully to treat a
variety of disease models, including gastroparesis, dumping, and short bowel
syndrome. Over the past 10 years or so, electrical stimulation of the GI tract
has received increasing attention among researchers and clinicians because of new
techniques, such as implantable devices, and promising results achieved in
treatment of gastroparesis and morbid obesity. The objective of this article is
to review the advances in electrical stimulation of the gastrointestinal tract.
First the electrophysiology of the GI tract and history of GI electrical
stimulation are introduced. Then various methods of electrical stimulation of the
stomach and small bowel in healthy animals and models of GI diseases are
reviewed. Finally clinical applications of electrical stimulation to GI disorders
and their possible mechanisms are discussed.
PMID- 29953382
TI - Laser Non-Contact Drug Delivery Methods: Mathematical and Experimental
Substantiation.
AB - This article outlines the existing methods for parenteral drug delivery. It also
presents novel alternative methods based on laser technologies, namely laser
impregnation and laser injection. A mathematical model is constructed to
calculate laser impregnator's technical parameters, such as the energy density of
laser radiation, pulse duration, and pulse repetition frequency. This model also
makes it possible to estimate the increase in the diffusion rate of drug
preparations when they are impregnated through multilayer structures, such as the
skin. Moreover, this article presents experimental results on Er.YAG laser
injection of various drug media, such as spirit solutions, aqueous solutions, and
ointments. These preparations were injected into gelatinous gel and autopsy skin
samples. Possible clinical application is considered for these laser
transcutaneous drug delivery methods.
PMID- 29953383
TI - Hemodynamic Parameters and Early Intimal Thickening in Branching Blood Vessels.
AB - Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in
medium to large blood vessels is a major contributor to heart disease, the
leading cause of death in the Western World. Balloon angioplasty with stenting,
bypass surgery, and endarterectomy (with or without patch reconstruction) are
some of the techniques currently applied to occluded blood vessels. On the basis
of the preponderance of clinical evidence that disturbed flow patterns play a key
role in the onset and progression of atherosclerosis and intimal hyperplasia, it
is of interest to analyze suitable hemodynamic wall parameters that indicate
susceptible sites of intimal thickening and/or favorable conditions for thrombi
formation. These parameters, based on the wall shear stress, wall pressure, or
particle deposition, are applied to interpret experimental/clinical observations
of intimal thickening. Utilizing the parameters as "indicator" functions,
internal branching blood vessel geometries are analyzed and possibly altered for
different purposes: early detection of possibly highly stenosed vessel segments,
prediction of future disease progression, and vessel redesign to potentially
improve long-term patency rates. At the present time, the focus is on the
identification of susceptible sites in branching blood vessels and their
subsequent redesign, employing hemodynamic wall parameters. Specifically, the
time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the
oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG)
are compared with experimental data for an aortoceliac junction. Then, the OSI,
wall particle density (WPD), and WSSAG are segmentally averaged for different
carotid artery bifurcations and compared with clinical data of intimal
thickening. The third branching blood vessel under consideration is the graft-to
vein anastomosis of a vascular access graft Suggested redesigns reduce several
hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient
[NPG]), thereby reducing the likelihood of restenosis, especially near the
critical toe region.
PMID- 29953384
TI - Control of Multifunctional Prosthetic Hands by Processing the Electromyographic
Signal.
AB - The human hand is a complex system, with a large number of degrees of freedom
(DoFs), sensors embedded in its structure, actuators and tendons, and a complex
hierarchical control. Despite this complexity, the efforts required to the user
to carry out the different movements is quite small (albeit after an appropriate
and lengthy training). On the contrary, prosthetic hands are just a pale
replication of the natural hand, with significantly reduced grasping capabilities
and no sensory information delivered back to the user. Several attempts have been
carried out to develop multifunctional prosthetic devices controlled by
electromyographic (EMG) signals (myoelectric hands), harness (kinematic hands),
dimensional changes in residual muscles, and so forth, but none of these methods
permits the "natural" control of more than two DoFs. This article presents a
review of the traditional methods used to control artificial hands by means of
EMG signal, in both the clinical and research contexts, and introduces what could
be the future developments in the control strategy of these devices.
PMID- 29953385
TI - A Review of Hydroxapatite and its use as a Coating in Dental Implants.
AB - At present, no standard manufacturing guideline exists for depositing
hydroxyapatite (HA) on implant surfaces. Although animal and in vitro studies
have reported on the benefits of using HA-coated implants as well as the risks of
dissolution, these short-term studies did not demonstrate that the dissolution of
the HA coating leads to a loss of implants. In addition, many in vivo and
clinical studies did not include the chemical and structural characterization of
the coatings, and thus comparisons between studies are difficult. In the clinics,
the recommendation is that HA-coated screw implants be used for the anterior
maxilla and posterior mandible where the bone depth exceeds 10 mm and when the
cortical layer is thinner and spongiosia is less dense. In the posterior maxilla
or when the cortical layer is very thin with low density, the use of HA-coated
cylindrical implants is recommended. However, there are concerns for using HA
coated implants. The clinician needs to take into consideration the enhanced
bacterial susceptibility of HA coatings compared with titanium implants. In
addition, the clinician needs to consider the possible failure of HA coatings as
a result of coating-substrate interfacial fracture. Finally, besides the surgical
skills, it is also important that the clinical investigators be well versed with
the materials characterization needed for HA-coated implants, the problems
associated with the current HA coatings, and the indications for use. In
addition, the correlation between well characterized coatings and their effect on
bone formation rate and long-term implant success, coating-implant interfacial
strength, and alternative superior coating process need to be investigated
further.
PMID- 29953386
TI - Review: Most Recent Advancements in Digital Signal Processing of the
Phonocardiogram.
AB - The objective of the present paper is to provide a detailed review of the most
recent developments in instrumentation and signal processing of digital
phonocardiography and heart auscultation. After a short introduction, the paper
presents a brief history of heart auscultation and phonocardiography, which is
followed by a summary of the basic theories and controversies regarding the
genesis of the heart sounds. The application of spectral analysis and the
potential of new time-frequency representations and cardiac acoustic mapping to
resolve the controversies and better understand the genesis and transmission of
heart sounds and murmurs within the heart-thorax acoustic system are reviewed.
The most recent developments in the application of linear predictive coding,
spectral analysis, time-frequency representation techniques, and pattern
recognition for the detection and follow-up of native and prosthetic valve
degeneration and dysfunction are also presented in detail. New areas of research
and clinical applications and areas of potential future developments are then
highlighted. The Final section is a discussion about a multidegree of freedom
theory on the origin of the heart sounds and murmurs, which is completed by the
authors' conclusion.
PMID- 29953387
TI - Review of Inverse Optimization for Functional and Physiological Considerations
Related to the Force-Sharing Problem.
AB - This paper is a review of the optimization techniques used for the solution of
the force-sharing problem in biomechanics; that is, the distribution of the net
joint moment to the force generating structures such as muscles and ligaments.
The solution to this problem is achieved by the minimization (or maximization) of
an objective function that includes the design variables (usually muscle forces)
that are subject to certain constraints, and it is generally related to
physiological or mechanical properties such as muscle stress, maximum force or
moment, activation level, etc. The usual constraints require the sum of the
exerted moments to be equal to the net joint moment and certain boundary
conditions restrict the force solutions within physiologically acceptable limits.
Linear optimization (objective and constraint functions are both linear
relationships) has limited capabilities for the solution of the force sharing
problem, although the use of appropriate constraints and physiologically
realistic boundary conditions can improve the solution and lead to reasonable and
functionally acceptable muscle force predictions. Nonlinear optimization provides
more physiologically acceptable results, especially when the criteria used are
related to the dynamics of the movement (e.g., instantaneous maximum force
derived from muscle modeling based on length and velocity histories). The
evaluation of predicted forces can be performed using direct measurements of
forces (usually in animals), relationship with EMG patterns, comparisons with
forces obtained from optimized forward dynamics, and by evaluating the results
using analytical solutions of the optimal problem to highlight muscle synergism
for example. Global objective functions are more restricting compared to local
ones that are related to the specific objective of the movement at its different
phases (e.g., maximize speed or minimize pain). In complex dynamic activities
multiobjective optimization is likely to produce more realistic results.
PMID- 29953388
TI - Critical Examination of Stress Shielding Evaluation of Hip Prostheses.
AB - In vitro evaluation of the load transfer of hip prostheses has been performed in
recent years for the purpose of understanding the stress shielding phenomena.
Over 200 papers were reviewed to determine if a standard exists to evaluate and
compare the performance of hip stems. Surprisingly, it was found that little
agreement exists in the testing protocol. This makes it very difficult to compare
the results reported in different investigations. In several cases very
incomplete data are reported about the testing conditions, thus making it
impossible to compare the results. This article focuses on: (1) how the loading
conditions should be chosen based on physiological loading in a way to give a
reproducible setup; (2) how the femur should be constrained; (3) how to generate
the same system of loads in the intact and the implanted femur; (4) how to define
a reference system; (5) how the specimen type and sample size are chosen; (6) the
advantages and limitations of the different strain measurement techniques; (7)
how the testing parameters have been chosen in the literature; and (8) how the
accuracy of the results has been reported in the literature.
PMID- 29953390
TI - Strategies to enhance NK cell function for the treatment of tumors and
infections.
AB - Natural killer (NK) cells are innate immune cells equipped with the ability to
rapidly kill stressed cells that are neoplastic or virally infected. These cells
are especially important in settings where these stressed cells downregulate MHC
class I molecules and evade recognition by cytotoxic T cells. However, the
activity of NK cells alone is often suboptimal to fully control tumor growth or
to clear viral infections. Thus, the enhancement of NK cell function is necessary
to fully harness their antitumor or antiviral potential. In this review, we
discuss how NK cell function can be augmented by the modulation of signal
transduction pathways, by the manipulation of inhibitory/activating receptors on
NK cells, and by cytokine-induced activation. We also discuss how some of these
strategies are currently impacting NK cells in the treatment of cancer and
infections.
PMID- 29953391
TI - Measuring T Cell Responses by Flow Cytometry-Based Fluorescence In Situ
Hybridization.
AB - T cells produce a wide variety of effector molecules in response to infections,
such as cytokines, chemokines, granzymes, and perforins. Because different
stimuli promote the production of specific effector molecules, T cell responses
come in different flavors. In addition, single-cell analysis of protein
production revealed that T cells respond heterogeneously to activation. To
unravel the regulatory mechanisms that determine T cell effector function, novel
methods were developed that simultaneously measure protein levels with the
corresponding mRNA. These flow cytometry-based fluorescence in situ hybridization
(Flow-FISH) technologies allow for multiparameter analysis with single-cell
resolution of both nucleic acids and proteins. Here, we review the currently
available methods of Flow-FISH and describe the possible applications thereof,
with a specific focus on T cells.
PMID- 29953392
TI - Characterization and Antioxidant Activity of an Exopolysaccharide Produced by
Rigidoporus microporus (Agaricomycetes).
AB - In this investigation we developed an optimal fermentation medium to produce an
exopolysaccharide (EPS) with antioxidant activity from Rigidoporus microporus.
Lactose and tryptone were chosen as the optimal carbon and nitrogen sources,
respectively, for EPS production, with a 6-day cultivation cycle. After removing
proteins through the use of the Sevag method, one EPS fraction was purified from
the culture filtrates by gel filtration chromatography on a Sepharose CL-6B
column. The preliminary chemical structure of the EPS fraction was determined by
Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry,
and nuclear magnetic resonance. The results indicated that the main structure of
the EPS consisted of beta-glucopyranose and mannopyranose. Furthermore,
conformational parameters such as molecular weight (Mw), intrinsic viscosity
([eta]), mean-square radii of gyration (Rg), and hydrodynamic radius (Rh) of the
EPS were characterized using a size exclusion chromatography-multiangle light
scattering-refractive index viscometry method. It showed that the EPS was a kind
of water-soluble polysaccharide with a moderate molecular weight (34.1 * 104) and
a flexible, linear random coil chain structure. The antioxidant activity tests
suggested that the EPS has great potential application as a natural antioxidant
material in foods and medicines.
PMID- 29953393
TI - Autophagy Inhibition Enhances SPCA-1 Cell Proliferation Inhibition Induced by By
1 from the Stout Camphor Medicinal Mushroom, Taiwanofungus camphoratus
(Agaricomycetes).
AB - Taiwanofungus camphoratus has been reported to have antitumor effects against
various cancer cells. The aim of this study was to investigate the direct
inhibitory effect of By-1 (3-isobutyl-l-methoxy-4-[4'-(3-methylbut-2
enyloxy)phenyl]-1H-pyrrole-2,5-dione), a compound from spent broth from submerged
cultures of T. camphoratus, on human lung adenocarcinoma cells and to determine
the molecular mechanism underlying this effect. The growth-inhibitory assay and
colony formation assay showed that cell viability was significantly decreased. A
By-1 concentration of 300 MUmol/L caused 73.55% cell death and at a concentration
of 240 MUmol/L led to a 58% reduction in the number of colonies. The wound
healing assay showed that the distance of migration was 0.3 times shorter than
that of untreated cells. Flow cytometry revealed that By-1 could suppress DNA
synthesis, cause cell cycle arrest at the S phase, and induce apoptosis in a
reactive oxygen species-dependent manner. Furthermore, the expression of caspase
3 and P53 was 4 times higher than that in untreated cells, and the antiapoptotic
protein Bcl-2 was decreased 2 times compared with the protein in untreated cells.
It is interesting to note that apoptosis and autophagy were both induced during
treatment with By-1, and autophagy inhibition decreased cell proliferation. By-1
potently inhibited the growth of SPCA-1 cells by inducing cell cycle arrest and
apoptosis. The combination of proapoptosis agents and antiautophagy agents could
effectively enhance anticancer efficacy, which may be a new strategy in treating
non-small cell lung cancer.
PMID- 29953389
TI - Tissue-Specific Control of Tissue-Resident Memory T Cells.
AB - Tissue-resident memory T (TRM) cells have emerged as a major component of T cell
biology. Recent investigations have greatly advanced our understanding of TRMs.
Common features have been discovered to distinguish memory T cells residing in
various mucosal and non-mucosal tissues from their circulating counterparts.
Given that most organs and tissues contain a unique microenvironment, local
signal-induced tissue-specific features are tightly associated with the
differentiation, homeostasis, and protective functions of TRMs. Here, we discuss
recent advances in the TRM field with a special emphasis on the interaction
between local signals and TRMs in the context of individual tissue environment.
PMID- 29953394
TI - Skin Mucus Protein Profile, Immune Parameters, Immune-Related Gene Expression,
and Growth Performance of Rainbow Trout (Oncorhynchus mykiss) Fed White Button
Mushroom (Agaricus bisporus) Powder.
AB - An 8-week feeding trial was performed to assess the effects of dietary white
button mushroom (Agaricus bisporus) powder (WBMP) on the mucosal immunity and
growth of rainbow trout (Oncorhynchus mykiss). Trout (n = 192; weight 13.76 +/-
1.17 g) were stocked in 12 cages (65 * 65 * 65 cm) placed in 4 raceways with a
flow-through water system. Trout were fed a basal diet (control group) or a basal
diet supplemented with 0.5%, 1%, or 2% WBMP for 8 weeks. Evaluation of total
protein levels and lysozyme activity in skin mucus revealed noticeable increases
in trout fed 1% or 2% WBMP (P < 0.05), but no significant difference was observed
with 0.5% WBMP administration (P > 0.05). The results of sodium dodecyl sulphate
polyacrylamide gel electrophoresis revealed alterations in the protein profile of
skin mucus following dietary administration of WBMP. Molecular studies showed a
noticeable increase (P < 0.05) in tumor necrosis factor-alpha messenger RNA in
the intestine of WBMP-fed trout, regardless of the inclusion level. Also, fish
receiving the 1% or 2% WBMP treatments had a remarkable increase in interleukin
(IL)-1beta expression compared with the control group (P < 0.05). In a similar
way, intestinal IL-8 expression was upregulated with the 1% and 2% WBMP
treatments (P < 0.05). However, no significant difference was found between the
control group and the 0.5% WBMP treatment group in the case of IL-8 gene
expression (P > 0.05). Furthermore, after 8 weeks of WBMP feeding, no improvement
was seen in the growth parameters of trout compared with those fish fed the
nonsupplemented diet (P > 0.05). These results hint at the potential
immunomodulatory effects of dietary WBMP.
PMID- 29953395
TI - Purification and Characterization of a Novel Protease from the Inky Cap Mushroom,
Coprinopsis atramentaria (Agaricomycetes).
AB - A novel protease was isolated from Coprinopsis atramentaria, which is, to our
knowledge, the first macromolecule to be purified from this species. The
protease, referred to as CAP, was purified through the use of ion exchange
chromatography on sulphopropyl-sepharose, diethylaminoethyl-cellulose, Q
Sepharose, and gel filtration on a Superdex 75 column. CAP is a monomelic protein
with a molecular mass of 32 kDa. The maximum activity of CAP was detected at pH
7.0 and 50 degrees C. The preferred pH of CAP demonstrated that it was a neutral
protease. Kinetic constants were determined under optimal reaction conditions,
using 1% casein as the substrate. We found Km and Vmax values of 7.98 mg . mL-1
and 215 MUg . mL-1 . min-1, respectively. Among the various metal ions tested,
Pb2+, Zn2+, Mn2+, Hg2+, Cu2+, and Cd2+ exerted dose-dependent inhibitory actions,
whereas Mg2+ exhibited a promoting action at all concentrations tested. Eight
inner peptide sequences were detected by liquid chromatography on an LTQ-Orbitrap
mass spectrometer and were identified using the Basic Local Alignment Search
Tool, which contains proteases from other sources. Alignment results showed that
2 of them were homologous to fungal cysteine proteases. The other 5 peptide
sequences also shared similarities with proteases of other origins. The isolation
of a novel protease from C. atramentaria in this study not only expands the
sources of proteases but also provides further information about this fungus.
PMID- 29953396
TI - Effects of a Commercial Supplement of Ophiocordyceps sinensis and Ganoderma
lucidum on Physiological Responses to Maximal Exercise in Healthy Young
Participants.
AB - Cordyceps sinensis (=Ophiocordyceps sinensis) and Ganoderma lucidum are 2
medicinal mushrooms that have been suggested to have the potential to enhance
exercise capacity. We used a commercial supplement combining a traditional
Chinese medicine and G. lucidum and tested its effects on human physical,
aerobic, and anaerobic capacities. Physical education students (n = 96; 43 women,
53 men; mean +/- standard deviation age, 26.3 +/- 3.21 years) were randomly
divided into 3 groups: low-dose treatment, high-dose treatment, and placebo.
Participants received the supplement or the placebo for 28-33 days. Both before
and after the intervention, the participants performed a graded maximum oxygen
consumption (Vo2max) test on a treadmill and a Wingate anaerobic cycle test (on a
different day). The following parameters were measured and recorded during the
maximal graded treadmill test: heart rate, oxygen consumption, respiratory
exchange ratio, and ventilation. The following parameters were calculated from
the Wingate anaerobic cycle test: maximal anaerobic power, mean anaerobic power,
and fatigue index. The supplements did not affect Vo2max or the physiological
responses upon maximal exercise during the graded treadmill test. In a similar
way, they had no effect on peak or mean power, or fatigue index, as measured by
the Wingate anaerobic test. A borderline interaction indicated a somewhat lower
heart rate at rest after treatment; however, post hoc analysis did not reveal any
further statistically significant differences (P = 0.047; F = 3.169). The
findings indicate that dual supplementation with C. sinensis and G. lucidum had
no effect on Vo2max, on physiological responses at peak exercise load during a
graded maximal treadmill test, or on the parameters of anaerobic capacity.
PMID- 29953398
TI - Extraction of Ergothioneine from Pleurotus eryngii and P. citrinopileatus
(Agaricomycetes) and Preparation of Its Product.
AB - Ergothioneine is an effective antioxidant and is abundant in species of genus
Pleurotus. This research focused on developing an ergothioneine extract from P.
eryngii and P. citrinopileatus under optimal extraction conditions. The hot-water
and 70% ethanol extractions yielded more ergothioneine than microwave,
ultrasonic, and autoclaving extractions. Hot-water extraction with optimal
conditions-125 rpm at 75 degrees C for 5 minutes-produced P. eryngii and P.
citrinopileatus extracts with 0.86 and 3.73 mg ergothioneine/g dry weight,
respectively. In addition to 50% of added maltodextrin, spray-dried products from
mushrooms contained 23.07-16.58% carbohydrates and 18.32-21.40% protein. The
microstructure of spray-dried products showed shrunken spheres with mean particle
diameters of 15.82-19.94 MUm. After in vitro simulated gastric and intestinal
digestion, the spray-dried P. eryngii and P. citrinopileatus products contained
88% and 91% residual ergothioneine, respectively. Overall, the spray-dried
products could be used as antioxidative supplements.
PMID- 29953397
TI - Antioxidant Properties and Yield of Wood Ear Mushroom, Auricularia polytricha
(Agaricomycetes), Cultivated on Rubberwood Sawdust.
AB - Mushroom cultivation has become an important component of agriculture, providing
food and contributing to the global economy. It uses vertical space and addresses
issues of food quality, health improvement, and environmental sustainability.
Auricularia mushrooms are popular ingredients in traditional Chinese cuisine. The
objective of this study was to determine yield and evaluate radical scavenging
capacity of A. polytricha cultivated on rubberwood sawdust on a large scale; we
measured total phenolic content; DPPH, hydroxyl, superoxide anion, and peroxyl
radical scavenging; and reducing power. Cultivation on rubberwood sawdust
produces an average of 4 harvests per bag and a biological efficiency of 80-82%.
The antioxidant capacity investigations revealed that the ethyl acetate fraction
was the most potent radical scavenger in all assays except that for superoxide
anions, whereas the aqueous fraction exhibited mild to moderate antioxidant
capacity in scavenging the various radicals. Artificial cultivation of A.
polytricha on rubberwood sawdust yields many sporophores with potent antioxidant
capacity.
PMID- 29953399
TI - Immunomodulatory and Antitumoral Properties of Ganoderma lucidum and Agaricus
brasiliensis (Agaricomycetes) Medicinal Mushrooms.
AB - Medicinal mushrooms are used in popular medicine largely as health promoters,
mainly because of their antitumor and immunomodulatory activities. Ganoderma
lucidum (lingzhi or reishi) and Agaricus brasiliensis are mushrooms that have
long been used for medicinal purposes. This study evaluated their
immunomodulatory and antitumor effects on mice fed a diet supplemented with G.
lucidum and A. brasiliensis mycelia obtained from solid-state fermentation. For
14 weeks the mice were fed chow containing 50% A. brasiliensis and G. lucidum
mycelia, using ground wheat as an excipient. The consumption of the supplemented
diet inhibited Sarcoma 180 tumor growth and caused important changes in the
immune system. The pattern of immune response shifted, increasing CD4+ and CD8+
and decreasing CD19+ cell populations. The restoration of a proper balance
between cellular and humoral immunity is an essential process for restraining
tumor growth. These results suggest that polysaccharides, such as beta-glucans
and other mushroom metabolites, possibly promote the T-cell dominance that is
imperative to restrain tumor growth.
PMID- 29953400
TI - Mycotheca of Edible and Medicinal Mushrooms at Herbarium SAF as a Potential
Source of Nutraceuticals and Cultivated Mushrooms.
AB - Basidiomycetes strains (n = 39) belonging to 9 genera in 8 families are kept in
the mycotheca of the Department of Agricultural, Food and Forest Sciences at the
University of Palermo (Palermo, Italy). All of the strains are medicinal
mushrooms, and some are of great commercial and nutraceutical interest.
PMID- 29953401
TI - Norbert Tietz, 13th November 1926-23rd May 2018.
PMID- 29953402
TI - Food addiction: is it a nosological category or a psychopathological dimension?
Preliminary results of an Italian study.
AB - Background Food addiction (FA) is a controversial concept, denoting the craving
for certain foods. Given the little information available, the aim of this study
was to evaluate the possible relationships between FA and full-blown and
subthreshold psychopathology or eating behaviors in subjects consulting
nutritional biologists. Materials and methods Three-hundred and fifty subjects
completed the following self-questionnaires: Yale Food Addiction Scale (YFAS),
Structured Clinical Interview for Mood Spectrum, Self-Report, Lifetime Version
(MOOD-SR-LT), Symptom Checklist-90-Revised (SCL-90-R), Structured Clinical
Interview for Anorexic-Bulimic Spectrum, Self-Report, Lifetime Version (ABS-SR
LT). Results Most of the subjects were women (n = 278) and the remaining were 72
men. A large proportion of the subjects (77.1%) had a YFAS score <3 and 22.9%
>=3, with no difference between men and women. The YFAS scores >=3 were
significantly and positively related to the all ABS-SR-LT domains, as well as to
three dimensions (Depression, Hypomania, Rhythmicity) of the MOOD-SR-LT, and some
SCL-90-R domains (Sensitivity, Psychoticism, General Symptom Index and Positive
Symptom). Conclusion Our data, while indicating that FA is related to different
subthreshold psychopathological domains, in particular, with both depressive and
manic symptoms, as well as with rhythmicity of mood spectrum, or with eating
subthreshold symptoms, would suggest that it might be a dimension underlying
different conditions or symptom clusters.
PMID- 29953403
TI - Health-promoting behaviors in nursing students: is it related to self-efficacy
for health practices and academic achievement?
AB - Background Nursing students play a role in promotion of public health as health
promoters and professional care providers. Therefore, health-promoting behaviors
in nursing students and their self-efficacy for health practices are important in
providing better services to patients and clients. With regard to the importance
of these factors in the academic progress of students, this study was conducted
to examine the level of health-promoting behaviors among nursing students and its
relationship with self-efficacy for health practices and academic achievement.
Methods This descriptive and correlational study was conducted on 217 nursing
students of a large university of medical sciences in the south of Iran in 2016.
Data were collected using the Persian version of the health promotion lifestyle
profile (HPLP II), self-rated abilities for health practices scale (SRAHPS) and
the grade point average of the students (levels A, B, C). Results The mean health
promoting behaviors (2.48 +/- 0.35) and self-efficacy for health practices of the
students (2.55 +/- 0.62) were moderate. The mean score of the students' academic
achievement was at level B (16.02 +/- 1.85). The health-promoting behaviors were
significantly correlated with self-efficacy for health practices (r = 0.623, p <
0.0001) and academic achievement (r = 0.285, p < 0.0001). Moreover, self-efficacy
for health practices was significantly correlated with academic achievement (r =
0.282, p < 0.0001). Conclusion The correlation between the health-promoting
behaviors and health self-efficacy with academic achievement can be a good basis
in devising health and educational programs for students. In planning for
promoting academic achievement and health-promoting behaviors of students, it is
essential to pay special attention to enhancement of self-efficacy for health
practices.
PMID- 29953404
TI - From under-eating to overindulgence - clinician perspectives on caring for
adolescents with eating disorders.
PMID- 29953405
TI - An examination of eating disorder education and experience in a 1-month
adolescent medicine rotation: what is sufficient to foster adequate self
efficacy?
AB - Objective Medical students and professionals report receiving limited
education/training related to treating eating disorders. Because medical
professionals are the point of initial contact for these patients and are
involved necessarily in their treatment, sufficient knowledge on identification
and intervention are imperative. This research set out to examine the impact of
the eating disorder education and experience offered through a 1-month Adolescent
Medicine rotation at a medical university on medical student/resident self
efficacy. Methods The 1-month rotation includes a standardized patient (SP)
simulation, 1.5 h of didactic education, and 1 day observing the MD, nutritionist
and psychologist within the outpatient Multidisciplinary Child/Adolescent Eating
Disorders Clinic. All residents' (n = 132) eating disorder self-efficacy was
assessed before (PRE) completing simulation and didactic session and again at the
end of the 1-month rotation (END). Self-efficacy was also assessed after
simulation and before the didactic session for group 1 (n = 92) and after
simulation and didactic session for group 2 (n = 40). Results For group 1, self
efficacy was not significantly impacted PRE to POST. For group 2, self-efficacy
significantly improved PRE to POST. POST to END changes were significant for both
groups; however, group 2 scored significantly better across all self-efficacy
areas at END. Conclusion Resident training in eating disorders requires more than
is offered in many residency programs. SP simulation is strengthened as an
effective training tool in assessing and promoting resident self-efficacy if it
is followed by didactic education. Clinical observation and extended practice
that includes ongoing guidance/feedback on performance is recommended in
fostering self-efficacy.
PMID- 29953406
TI - Changes in weight, physical activity and its theory-based psychosocial correlates
within an adolescent bariatric clinic: contrasts with adults with extreme
obesity.
AB - Albeit their practical implications, psychosocial correlates of physical activity
and related weight loss in the treatment of extreme obesity have been only
sparsely addressed in adults; and even more minimally focused upon in
adolescents. This research contrasted results of a 6-month social cognitive
theory-based physical activity-support protocol along with standard nutrition
counseling in groups of adolescents (n = 19; agemean = 15.4 years) and adults (n
= 26, agemean = 44.7 years) with class 3 (extreme) obesity [overall body mass
index (BMI)mean = 53.4 kg/m2, standard deviation (SD) = 8.2]. Although baseline
total mood disturbance scores were significantly greater in both groups when
contrasted with age-corresponding normative values, between-group scores did not
significantly differ. BMI and physical activity changes over 3 and 6 months were
significantly more favorable in the adult group. There were significant overall
improvements in exercise self-efficacy, physical activity self-regulation and
total mood disturbance scores, however, the self-efficacy and self-regulation
increases were significant in only the adult group. Inverse relationships between
changes in physical activity and BMI were stronger in the adult group. Regardless
of group, simultaneous entry of changes in exercise self-efficacy, physical
activity self-regulation and total mood disturbance scores, over both 3 and 6
months, significantly predicted physical activity changes (R2-values = 0.45-0.75,
p-values < 0.001). In each model, self-regulation change was the most salient of
those three psychosocial predictors. Although findings suggested that
psychosocial correlates of physical activity, leading to weight change, are
similar in adolescents and adults with extreme obesity, facilitation of larger
effect sizes and/or foci on additional theory-based determinants may be required
for clinically meaningful treatment outcomes in adolescents.
PMID- 29953407
TI - Evaluation of Mn-superoxide dismutase and catalase gene expression in childhood
obesity: its association with insulin resistance.
AB - Background Obesity is associated with oxidative stress. Superoxide dismutase
(SOD) is the first line of defense against reactive oxygen species (ROS),
eliminating the strong superoxide radical and producing H2O2, which can then be
degraded by catalase (CAT). The main objective of this study was to evaluate the
gene expression antioxidant enzymes (Mn-SOD and CAT) in peripheral blood
mononuclear cells (PBMCs) of obese and normal-weight children, and its
association with anthropometric and biochemical parameters. Methods Thirty obese
and 30 control subjects between the ages of 8 and 16 years were enrolled in this
study. Serum insulin levels were measured using enzyme-linked immunosorbent assay
(ELISA), and insulin resistance was calculated using the homeostasis model
assessment of insulin resistance (HOMA-IR). Biochemical parameters were also
measured. PBMCs of the subjects were separated and Mn-SOD and CAT gene expression
was measured using real-time polymerase chain reaction (PCR). Results Mn-SOD and
CAT gene expression was significantly lower in the obese group compared with the
control group (p<0.01). Also, a positive correlation was observed between the
gene expression of Mn-SOD and CAT and body mass index (BMI), fasting blood sugar,
insulin resistance, low density lipoprotein-cholesterol (LDL-C) cholesterol,
triglycerides (TG) and systolic blood pressure (SBP). Conclusions Induction of
antioxidants, especially Mn-SOD and CAT, can lead to reduction of oxidative
stress and prevent the complications of obesity in children.
PMID- 29953408
TI - Random serum free cortisol and total cortisol measurements in pediatric septic
shock.
AB - Background The aim of the study was to examine the relationship between serum
total cortisol (TC) and free cortisol (FC) levels in children with septic shock
and the relationship of these levels with baseline illness severity. Methods A
sub-study of a randomized controlled trial (RCT) of hydrocortisone vs. placebo in
pediatric septic shock conducted in seven academic pediatric intensive care units
(PICUs) in Canada on children aged newborn to 17 years. Thirty children with
septic shock had serum sent for TC and FC measurement within 6 h of meeting the
study eligibility criteria. Results Baseline FC and TC levels were strongly
correlated with baseline Pediatric Risk of Mortality (PRISM) score (R2=0.759,
p<0.001; R2=0.717, p<0.001) and moderately correlated with admission Vasotropic
Inotropic Score (VIS) (R2=0.489, p<0.001; R2=0.316, p<0.001). Serum TC levels
were highly correlated with FC levels (R2=0.92, p<0.001) and showed strong
agreement (R2=0.98, p<0.001 on a Bland-Altman plot). The ratio of FC to TC
moderately correlated with TC levels (R2=0.46, p<0.001) but did not correlate
with baseline albumin levels (R2=0.19, p=0.13). Conclusions Random TC and FC
levels are strongly correlated, show strong agreement and are reflective of
illness severity in children with septic shock. As such, isolated FC measurement
does not appear to provide added information relative to TC in acutely ill
children with septic shock.
PMID- 29953409
TI - Severe consumptive hypothyroidism caused by multiple infantile hepatic
haemangiomas.
AB - Background Infantile hepatic haemangiomas (IHHs) produce an excess of the thyroid
hormone inactivating enzyme type-3 iodothyronine deiodinase (D3), leading to
rapid degradation of thyroid hormones and consumptive hypothyroidism. The L
thyroxine replacement dose in patients with consumptive hypothyroidism is
inappropriately higher than that in congenital hypothyroidism. Case presentation
A 4-month-old boy presented with abdominal distention. Thyroid function tests
(TFTs) revealed an elevated thyroid-stimulating hormone (TSH) level of 177 mU/L,
normal free thyroxine (fT4) of 1.23 ng/dL, low free tri-iodothyronine (fT3) of
1.55 pg/mL and increased reverse T3 (rT3) of 1240 ng/dL. Abdominal ultrasound and
magnetic resonance imaging (MRI) revealed multiple IHHs. Based on his TFTs,
ultrasonography and MRI evidence, he was diagnosed with consumptive
hypothyroidism, and L-thyroxine replacement at 15 MUg/kg/day was started. The L
thyroxine dose was increased gradually to 35 MU/kg/day until a stabilising
euthyroid status was achieved. By the age of 8 months, the TSH concentration was
decreased to normal levels; the L-thyroxine dose was gradually reduced and
finally discontinued at the age of 12 months. Repeat abdominal ultrasound and MRI
revealed a reduction in the number and size of the haemangiomas. The TFTs were at
normal reference levels. The patient remains in active follow-up. Conclusions
Neonatal screening for congenital hypothyroidism is usually negative in cases of
IHH, as seen in our case. A high index of suspicion is necessary to diagnose
hypothyroidism in cases of IHH. The present case required very high doses of
levothyroxine to achieve a euthyroid status. In cases of hypothyroidism in the
first year of life with consumptive hypothyroidism caused by hepatic haemangioma,
aggressive L-thyroxine replacement is required with no upper limit. The dose
should be increased gradually until a stabilising euthyroid status is achieved.
PMID- 29953410
TI - Detection of distant metastasis at the time of ablation in children with
differentiated thyroid cancer: the value of pre-ablation stimulated
thyroglobulin.
AB - Background The present study was designed to determine the value of pre-ablation
stimulated thyroglobulin (s-Tg) in predicting distant metastasis (DM) at the time
of ablation in children with differentiated thyroid cancer. Methods From August
2009 to December 2016, consecutive children with differentiated thyroid cancer
undergoing remnant ablation were retrospectively analyzed. Serum s-Tg was
measured with the high-sensitive electrochemiluminescence immunoassay during
hypothyroidism at ablation just before the ablative radioactive iodine (131I)
administration. Post-ablation, whole body planar scintigraphy was obtained 5 days
after administration of ablation activity of 131I. Single photon emission
computed tomography/low-dose computed tomography (SPECT/CT) was added for
children whose planar findings were inconclusive. Receiver-operating
characteristics (ROC) curve analysis was employed to find a cut-off level of pre
ablation s-Tg as a predictor of DM at the time of ablation. Results Fifty-seven
children were included for the analysis. Metastases were noticed on post-ablation
scintigraphy in 20 (35%) children: five post-operative residual neck lymph node
metastases, four post-operative residual neck lymph node and lung metastases,
three mediastinal lymph node and lung metastases and eight lung metastases. A
significant difference in pre-ablation s-Tg levels was found in children with DM
compared with those without DM, 603.5 vs. 5.7 ng/mL, respectively. A pre-ablation
s-Tg level of 156 ng/mL was established as the optimal cut-off point to predict
DM. Conclusions This study demonstrated that pre-ablation s-Tg could potentially
act as a predictor of DM at the time of ablation in children with differentiated
thyroid cancer. We also propose a specific pre-ablation s-Tg cut-off value of 156
ng/mL as an optimal threshold for practical use.
PMID- 29953411
TI - Clinical management of childhood hyperthyroidism with and without Down syndrome:
a longitudinal study at a single center.
AB - Background The approach to the clinical management of Graves' disease (GD) is
debatable. This study aimed to identify predictors of remission in pediatric GD.
Methods A longitudinal study of 36 children and adolescents with GD followed from
1997 to 2017 at a single tertiary hospital was performed. Clinical and
biochemical parameters, including comorbidities, treatment with anti-thyroid
drugs (ATD) or definitive therapy (radioiodine [RIT] and thyroidectomy), and
remission as the main outcome were collected. We performed a multivariable
logistic regression analysis to identify likely predictors of remission. Results
Among patients, most were female, in late puberty, with exuberant symptoms at
onset. Eleven also suffered from Down syndrome (DS). Thirty-four patients (94%)
started on methimazole from disease onset, and 25 (69%) received it as the only
therapy, with a mean duration of 2.7+/-1.8 years. Six changed to RIT and three
underwent thyroidectomy; no DS patient received definitive therapy. Remission was
higher in DS patients (45% vs. 25%, p=0.24), but afterwards (3.9+/-2.5 vs. 2.3+/
1.4 years, p<0.05); there was no significance in relapsing (20% vs. 15%). Females
were less likely to reach remission (p<0.05); serum free thyroxine at onset was
higher (p<0.05) in patients who required definitive therapy. Thyroid-stimulating
immunoglobulin (TSI) values normalized in exclusively ATD therapy, especially
from 2 years on (p<0.05). Conclusions Males were more likely to achieve
remission. TSI values may normalize in GD, notably from the second year of
treatment. DS children may benefit with conservative management in GD.
PMID- 29953412
TI - Self-assessment of pubertal development in a puberty cohort.
AB - Background We evaluated the inter-rater agreement between self-assessed Tanner
staging and clinical examination and the intra-individual agreement of self
assessed information on various puberty markers in late adolescents from the
longitudinal nationwide Puberty Cohort, a sub-cohort of the Danish National Birth
Cohort (DNBC). Methods We invited 715 children from the ongoing Puberty Cohort
between June 2016 and January 2017. In total, 366 children (51%) returned an add
on questionnaire identical to the questionnaire used to collect information on
puberty markers, including Tanner staging, in the Puberty Cohort. Of these, 197
(54%) also participated in a clinical examination with Tanner staging. We used
percentage agreement and weighted kappa statistics to evaluate the inter-rater
and intra-individual agreement. Results Due to late entry, more than 75% of
children were Tanner stage 4 or above at clinical examination. In girls, the
inter-rater agreement for pubic hair and breast staging was 54% and 52%,
respectively, yielding weighted kappas of fair strength. In boys, pubic hair and
genital staging agreed in 55% and 33%, respectively, corresponding to weighted
kappas of fair to moderate strength. Boys tended to underestimate genitalia
staging consistently. The intra-individual agreement on Tanner staging was 75-77%
in girls and 69% in boys, whereas the intra-individual agreement on axillary hair
and acne was above 92%. Conclusions Self-assessment of late stages of pubertal
development may be misclassified, leading to random errors in studies of puberty
timing. However, self-assessment continues to serve as an important time- and
cost-saving tool in large prospective puberty cohorts.
PMID- 29953413
TI - CircSNCA downregulation by pramipexole treatment mediates cell apoptosis and
autophagy in Parkinson's disease by targeting miR-7.
AB - We aimed to explore the mechanism of pramipexole (PPX) actions in the treatment
of Parkinson's disease (PD). Genes related to PD and PPX were screened through
bioinformatics retrieval. The PD model was constructed by applying 1-methyl-4
phenylpyridinium (MMP+). The RNA expression levels of circSNCA, SNCA, apoptosis
related genes (BCL2, CASP3, BAX, PTEN and P53) and miR-7 were detected by qRT
PCR. Protein expression was determined by western blot. The interactions between
circSNCA-miR-7-SNCA were verified by dual luciferase assay and immunofluorescence
localization. Cell viability was determined by MTT assay. SNCA and circSNCA
expression levels in PD were downregulated after PPX treatment, consistent with
the levels of pro-apoptotic genes. CircSNCA increased SNCA expression by
downregulating miR-7 in PD as a competitive endogenous RNA (ceRNA). Lower
circSNCA expression was associated with the reduced expression of pro-apoptotic
(CASP3, BAX, PTEN and P53) proteins. CircSNCA downregulation could decrease
apoptosis and induce autophagy in PD. In conclusion, the downregulation of
circSNCA by PPX treatment reduced cell apoptosis and promoted cell autophagy in
PD via a mechanism that served as a miR-7 sponge to upregulate SNCA.
PMID- 29953414
TI - Aged cells in human skeletal muscle after resistance exercise.
AB - : It remains unclear how exercise, as an entropic event, brings benefit against
human aging. Here we examined longitudinal changes of p16Ink4a+ senescent cells
in skeletal muscle of young men (aged 22.5+/-1.7 y) before and after resistance
exercise (0 h and 48 h) with multiple biopsies at two different protein
availabilities: low protein (14%) and isocaloric high protein (44%) supplemented
conditions. Immunohistochemistry analysis of muscle cross-sections using p16Ink4a
and CD34 antibodies confirmed that the detected senescent cells were endothelial
progenitor cells. Leukocyte infiltration into skeletal muscle increased during
resistance exercise. The senescent cells in muscle decreased (-48%, P < 0.01)
after exercise for 48 h. Low protein supplementation resulted in greater
infiltrations of both CD68+ phagocytic macrophage and leukocyte, further
decreased p16Ink4a+ senescent cells (-73%, P < 0.001), and delayed increases in
regenerative CD163+ macrophage in skeletal muscle, compared with high protein
supplemented condition. Significant gain in muscle mass after 12 weeks of
training occurred only under high protein supplemented condition. CONCLUSION:
Rapid senescent cell clearance of human skeletal muscle during resistance
exercise seems to associate with enhanced in situ phagocytosis. High protein
availability accelerates resolution of muscle inflammation and promotes muscle
increment after training.
PMID- 29953415
TI - High-accuracy determination of internal circadian time from a single blood
sample.
AB - BACKGROUND: The circadian clock is a fundamental and pervasive biological program
that coordinates 24-hour rhythms in physiology, metabolism, and behavior, and it
is essential to health. Whereas therapy adapted to time of day is increasingly
reported to be highly successful, it needs to be personalized, since internal
circadian time is different for each individual. In addition, internal time is
not a stable trait, but is influenced by many factors, including genetic
predisposition, age, sex, environmental light levels, and season. An easy and
convenient diagnostic tool is currently missing. METHODS: To establish a
validated test, we followed a 3-stage biomarker development strategy: (a) using
circadian transcriptomics of blood monocytes from 12 individuals in a constant
routine protocol combined with machine learning approaches, we identified
biomarkers for internal time; and these biomarkers (b) were migrated to a
clinically relevant gene expression profiling platform (NanoString) and (c) were
externally validated using an independent study with 28 early or late
chronotypes. RESULTS: We developed a highly accurate and simple assay (BodyTime)
to estimate the internal circadian time in humans from a single blood sample. Our
assay needs only a small set of blood-based transcript biomarkers and is as
accurate as the current gold standard method, dim-light melatonin onset, at
smaller monetary, time, and sample-number cost. CONCLUSION: The BodyTime assay
provides a new diagnostic tool for personalization of health care according to
the patient's circadian clock. FUNDING: This study was supported by the
Bundesministerium fur Bildung und Forschung, Germany (FKZ: 13N13160 and 13N13162)
and Intellux GmbH, Germany.
PMID- 29953417
TI - Moderate Traumatic Brain Injury Alters the Gastrointestinal Microbiome in a Time
Dependent Manner.
AB - The microbiome is defined as the collective genomes of the microbes (composed of
bacteria, bacteriophage, fungi, protozoa and viruses) that colonize the human
body, and alterations have been associated with a number of disease states.
Changes in gut commensals can influence the neurologic system via the brain-gut
axis, and systemic insults such as trauma or traumatic brain injury (TBI) may
alter the gut microbiome. The objective of this study was to evaluate the gut
microbiome in a pre-clinical TBI cortical impact model. Male rats underwent
craniotomy and randomized to a sham group (n = 4), or a moderate TBI (n = 10)
using a pneumatic impactor. MRI and behavioral assessments were performed pre-TBI
and on days 2, 7 and 14 days thereafter. Microbiome composition was determined
with 16 s rRNA sequencing from fecal sample DNA pre-TBI and 2 hrs, 1, 3, and 7
days afterwards. Alpha- and beta- bacterial diversity, as well as organizational
taxonomic units (OTUs) were determined. Significant changes in the gut microbiome
were evident as early as 2 hrs after TBI as compared to pre-injured samples and
sham rats. While there were varying trends among the phylogenetic families across
time, some changes persisted through 7 days in the absence of therapeutic
intervention. While large structural lesions and behavioral deficits were
apparent post-TBI, there were modest but significant decreases in alpha
diversity. Moreover, both changes in representative phyla and alpha-diversity
measures were significantly correlated with MRI-determined lesion volume. These
results suggest that changes in the microbiome may represent a novel biomarker to
stage TBI severity and predict functional outcome.
PMID- 29953416
TI - Neuropilin-1 upregulation elicits adaptive resistance to oncogene-targeted
therapies.
AB - Cancer cell dependence on activated oncogenes is therapeutically targeted, but
acquired resistance is virtually unavoidable. Here we show that the treatment of
addicted melanoma cells with BRAF inhibitors, and of breast cancer cells with
HER2-targeted drugs, led to an adaptive rise in neuropilin-1 (NRP1) expression,
which is crucial for the onset of acquired resistance to therapy. Moreover, NRP1
levels dictated the efficacy of MET oncogene inhibitors in addicted stomach and
lung carcinoma cells. Mechanistically, NRP1 induced a JNK-dependent signaling
cascade leading to the upregulation of alternative effector kinases EGFR or
IGF1R, which in turn sustained cancer cell growth and mediated acquired
resistance to BRAF, HER2, or MET inhibitors. Notably, the combination with NRP1
interfering molecules improved the efficacy of oncogene-targeted drugs and
prevented or even reversed the onset of resistance in cancer cells and tumor
models. Our study provides the rationale for targeting the NRP1-dependent
upregulation of tyrosine kinases, which are responsible for loss of
responsiveness to oncogene-targeted therapies.
PMID- 29953418
TI - A Prospective Study of the Safety and Efficacy of a Microneedle Fractional
Radiofrequency System for Global Facial Photoaging in Chinese Patients.
AB - BACKGROUND: Facial photoaging has become a major cosmetic concern, and the
microneedle fractional radiofrequency system (MFRS) is a novel method for
rejuvenation that combines radiofrequency and microneedles. OBJECTIVE: This study
prospectively evaluated the efficacy and safety of an MFRS in the treatment of
facial photoaged skin in Chinese patients. MATERIALS AND METHODS: Twenty-seven
patients with moderate facial photoaging were recruited and received 3 treatments
at 4-week intervals. Blinded clinical assessment was performed by 2 independent
dermatologists on a 5-point global photoaging scale (GPS). Patients were also
questioned on the extent of improvement of rhytides, skin tightening, and
complexion with a 4-point global aesthetic improvement scale (GAIS) and
satisfaction based on a 5-point scale. Adverse events and pain scores were also
evaluated. RESULTS: Compared with the baseline, there was a significant
improvement in facial photoaged skin after 3 treatments, and these positive
outcomes were maintained up to the 6-month follow-up, according to the GPS and
GAIS scores. Most patients were satisfied with the treatment and reported mild to
moderate pain and adverse effects. CONCLUSION: This MFRS is effective for facial
skin rejuvenation in Chinese patients. The therapy also seems safe and well
tolerated.
PMID- 29953419
TI - A Multiple Recurrent Keratoacanthoma of the Lower Leg After Repeated Wide
Excision and Mohs Micrographic Surgery.
PMID- 29953420
TI - Effect of hypobaria and hyperoxia during sepsis on survival and energy
metabolism.
AB - BACKGROUND: Injured warfighters air evacuated to tertiary medical care facilities
are subjected to many stresses that may promote the development of sepsis. In
this study, we tested the hypothesis that exposure to "in-flight" hypobaria
and/or hyperoxia within 24 hours after onset of intra-abdominal infection in rats
accelerates the development and/or severity of sepsis and neurologic injury in
survivors. METHODS: Sprague-Dawley rats underwent cecal ligation/puncture (CLP)
or sham procedures. Twenty-four hours later, rats were then placed in hypobaric
chambers for 6 hours and assigned to normobaric conditions and maintained at
either 21% or 100% O2, or under hypobaric conditions (pressure equivalent to an
altitude of 8,000 ft) but maintained under either 28% or 100% O2. Two days after
CLP or sham, blood samples were obtained for cytokine levels, and mitochondria
were isolated from the brain and heart of a subset of animals for analysis of
mitochondrial oxygen consumption. Animals were also evaluated for neuromotor
impairment before and 15 days postsurgery. RESULTS: Among the 70 rats studied,
16.7% of CLP but none of the sham-treated rats died. All of the CLP but none of
the sham rats had evidence of peritonitis at 2 days. Twenty percent (6 of 30) CLP
rats undergoing hypobaria versus 12.5% (3 of 24) of CLP rats exposed to
normobaria died (p = 0.715) while 12% (3 of 25) of CLP rats exposed to hyperoxia
versus 20.7% (6 of 29) of CLP rats exposed to normoxia died (p = 0.48). The ratio
of mitochondrial ATP-generating O2 consumption to resting respiration was higher
in the CLP plus hypobaria under 100% compared with shams. The only difference in
H2O2 production was observed in mitochondria from CLP rats exposed to hyperoxia
under normobaric conditions. Composite neurologic scores obtained 15 days
postinjury were lower than those at baseline for shams. CONCLUSION: We conclude
that neither "in-flight" hyperoxia nor hypobaria exacerbate sepsis or neurologic
injury.
PMID- 29953421
TI - Toward Systematic Screening for Persistent Hepatitis E Virus Infections in
Transplant Patients.
AB - BACKGROUND: Persistent hepatitis E virus genotype 3 (HEV G3) infections affect
solid organ transplant (SOT) recipients and hematopoietic stem cell transplant
(HSCT) recipients, but the burden in these cohorts in the United Kingdom is
unknown. We established an audit to determine the point prevalence of HEV viremia
in SOT and HSCT patients in the United Kingdom and compare different testing
approaches to inform screening strategies. METHODS: Between January 5, 2016, and
September 21, 2016, 3044 patients undergoing therapeutic drug monitoring at a
single transplant center were screened for HEV ribonucleic acid (RNA) in
minipools. A total of 2822 patients who could be characterized included 2419 SOT
patients, 144 HSCT patients and 259 patients with no available transplant
history. HEV RNA-positive samples were characterized by serology and genomic
phylogeny. HEV antigen (HEV-Ag) testing was performed on RNA-positive samples,
420 RNA-negative samples and 176 RNA-negative blood donor samples. RESULTS:
Nineteen of 2822 patients were viremic with G3 HEV giving a prevalence of 0.67%.
The median alanine aminotransferase was significantly higher in the HEV viremic
patients (P < 0.0001); however, 2 viremic patients had an alanine
aminotransferase value within the normal range at the time of screening. The HEV
Ag assay identified 18/19 viremic patients and all those patients with proven
viremia longer than 4 weeks. CONCLUSIONS: Transplant recipients in the United
Kingdom are at a low but significant risk of HEV infection. HEV-Ag detection
could be an alternative to RNA detection where the goal is to identify
established persistent HEV infection, particularly where expertise, facilities,
or cost prohibit RNA testing.
PMID- 29953422
TI - Superior Hypertension Management in Pediatric Kidney Transplant Patients After
Native Nephrectomy.
AB - BACKGROUND: Native nephrectomy in pediatric kidney transplant recipients is
performed for multiple indications. Posttransplant hypertension requiring medical
management is common, and the effect of native nephrectomy on posttransplant
hypertension is poorly studied. Our aim is to evaluate the impact of native
nephrectomy on posttransplant hypertension. METHODS: One hundred thirty-six
consecutive pediatric kidney transplant recipients from 2007 to 2012 were studied
at a single institution and divided into 2 groups: no nephrectomy and native
nephrectomy (unilateral and bilateral nephrectomy). Antihypertensive medication
use was evaluated before nephrectomy/transplant, at discharge from transplant and
at 1, 3, and 5 years posttransplant. RESULTS: In a bivariate analysis,
nephrectomy was associated with a significant reduction in the percentage of
patients requiring antihypertensive medication at the time of discharge (27.3%)
and 1 year posttransplant (10.7%) as compared with patients without nephrectomy
(71.7%, and 50%, respectively, P < 0.05). This trend toward reduction in
antihypertensive medication in the nephrectomy group as compared with the no
nephrectomy group persisted at 3 (18.6% versus 43.2%) and 5 years (19.7% versus
37.5%) posttransplant. Multivariable logistic regression demonstrated that
patients without native nephrectomy had higher odds of requiring antihypertensive
medication at the time of discharge (3.3) and 1 year (5.2) as compared with
patients who underwent native nephrectomy (P = 0.036 and P = 0.013,
respectively). CONCLUSIONS: Native nephrectomy reduces the odds of needing
antihypertensive medication after transplant. The impact of native nephrectomy is
crucial to the comprehensive management of pediatric transplant recipients where
medication compliance is challenging and lifelong hypertension is known to
negatively impact cardiovascular health.
PMID- 29953423
TI - Impact of Willingness to Accept Hepatitis C Seropositive Kidneys Among Hepatitis
C RNA-Positive Waitlisted Patients.
AB - BACKGROUND: Kidney transplantation from hepatitis C seropositive (HCV+) donors
may benefit hepatitis C RNA-positive (RNA+) candidates, but it is unclear how the
willingness to be listed for and accept such kidneys affects waitlist and
transplant outcomes. METHODS: In a single-center retrospective analysis, HCV+
transplant candidates (N = 169) listed from March 2004 to February 2015 were
evaluated. All RNA+ candidates were offered the option to be listed for HCV+
donors. RNA- candidates were listed only for HCV- donors. RESULTS: Fifty-seven
patients (51% of all RNA+ transplant candidates) willing to accept HCV+ donors
were listed for both HCV+ and HCV- donor kidneys. During 6-year follow up, 43
(75%) of 57 patients accepting HCV+ versus 19 (35%) of 55 patients not accepting
HCV+ received a deceased donor kidney transplant (P < 0.0001). Multivariable
analysis demonstrated that willingness to be listed for and accept HCV+ kidneys
was associated with receiving deceased donor kidney transplant (P = 0.0016).
Fewer patients accepting HCV+ donors (7 [12%] vs 16 [29%]) were removed from the
list due to death or deteriorated medical condition (P = 0.0117). Posttransplant
patient and graft survival rates were not significantly different. Overall
patient survival since the listing (combined waitlist and posttransplant
survival) was similar among the groups. CONCLUSIONS: HCV RNA+ candidates had
better access to transplantation and similar overall survival before the era of
widespread use of direct-acting anti-HCV agents.
PMID- 29953424
TI - Ouabain Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury.
AB - BACKGROUND Ouabain, an inhibitor of Na+/K+-ATPase, is a type of endogenous
hormone synthesized in the adrenal cortex and hypothalamus. Previous studies
found that ouabain potently inhibited inflammatory reactions and regulated
immunological processes. Our present study aimed to investigate the therapeutic
role of ouabain on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in
mice. MATERIAL AND METHODS Ouabain (0.1 mg/kg) or vehicles were intraperitoneally
injected into male C57BL/6J mice once a day for 3 consecutive days. One hour
after the last injection of ouabain, LPS (5 mg/kg) was administrated through
intranasal instillation to induce ALI. 6 hours and 24 hours later,
bronchoalveolar lavage fluid (BALF) and lung tissues were harvested to detect the
protective effects of ouabain, including protein concentration, inflammation cell
counts, lung wet-to-dry ratio, and lung damage. RESULTS The results showed that
ouabain attenuated LPS-induced ALI in mice, which was indicated by alleviated
pathological changes, downregulated TNF-alpha, IL-1beta, and IL-6 production,
inhibited neutrophils infiltration and macrophages, and ameliorated pulmonary
edema and permeability. Further results found the activation of nuclear factor
kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling
pathways were suppressed by ouabain in LPS-induced ALI. CONCLUSIONS These results
suggest that ouabain negatively modulates the severity of LPS-induced ALI.
PMID- 29953426
TI - Notice to Readers: Ongoing Analysis of Suicide Rates Data by Occupational Group
from Results Reported in MMWR.
PMID- 29953425
TI - Outbreaks Associated with Untreated Recreational Water - United States, 2000
2014.
AB - Outbreaks associated with untreated recreational water can be caused by
pathogens, toxins, or chemicals in fresh water (e.g., lakes, rivers) or marine
water (e.g., ocean). During 2000-2014, public health officials from 35 states and
Guam voluntarily reported 140 untreated recreational water-associated outbreaks
to CDC. These outbreaks resulted in at least 4,958 cases of disease and two
deaths. Among the 95 outbreaks with a confirmed infectious etiology, enteric
pathogens caused 80 (84%); 21 (22%) were caused by norovirus, 19 (20%) by
Escherichia coli, 14 (15%) by Shigella, and 12 (13%) by Cryptosporidium.
Investigations of these 95 outbreaks identified 3,125 cases; 2,704 (87%) were
caused by enteric pathogens, including 1,459 (47%) by norovirus, 362 (12%) by
Shigella, 314 (10%) by Cryptosporidium, and 155 (5%) by E. coli. Avian
schistosomes were identified as the cause in 345 (11%) of the 3,125 cases. The
two deaths were in persons affected by a single outbreak (two cases) caused by
Naegleria fowleri. Public parks (50 [36%]) and beaches (45 [32%]) were the
leading settings associated with the 140 outbreaks. Overall, the majority of
outbreaks started during June-August (113 [81%]); 65 (58%) started in July.
Swimmers and parents of young swimmers can take steps to minimize the risk for
exposure to pathogens, toxins, and chemicals in untreated recreational water by
heeding posted advisories closing the beach to swimming; not swimming in
discolored, smelly, foamy, or scummy water; not swimming while sick with
diarrhea; and limiting water entering the nose when swimming in warm freshwater.
PMID- 29953427
TI - Prevalence and Predictors of Provider-Initiated HIV Test Offers Among
Heterosexual Persons at Increased Risk for Acquiring HIV Infection - Virginia,
2016.
AB - Since 2006, CDC has recommended routine, provider-initiated human
immunodeficiency virus (HIV) screening (i.e., HIV screening at least once in
lifetime) for all patients aged 13-64 years in all health care settings (1).
Whereas evidence related to the frequency of HIV testing is available, less is
known about the prevalence and predictors of providers' HIV test offers to
patients (2). National HIV Behavioral Surveillance (NHBS) data from Virginia were
used to examine the prevalence and predictors of provider-initiated HIV test
offers to heterosexual adults aged 18-60 years at increased risk for HIV
acquisition. In a sample of 333 persons who visited a health care provider in the
12 months before their NHBS interview, 194 (58%) reported not receiving an HIV
test offer during that time, approximately one third of whom (71, 37%) also
reported never having had an HIV test in their lifetime. In multivariable
analysis, the prevalence of HIV test offers was significantly lower among men
than among women (adjusted prevalence ratio [aPR] = 0.72; 95% confidence interval
[CI] = 0.53-0.97). Provider-initiated HIV test offers are an important strategy
for increasing HIV testing among heterosexual populations; there is a need for
increased provider-initiated HIV screening among heterosexual adults who are at
risk for acquiring HIV, especially men, who were less likely than women to be
offered HIV screening in this study.
PMID- 29953428
TI - Fatal Sepsis Associated with Bacterial Contamination of Platelets - Utah and
California, August 2017.
AB - During August 2017, two separate clusters of platelet transfusion-associated
bacterial sepsis were reported in Utah and California. In Utah, two patients died
after platelet transfusions from the same donation. Clostridium perfringens
isolates from one patient's blood, the other patient's platelet bag, and donor
skin swabs were highly related by whole genome sequencing (WGS). In California,
one patient died after platelet transfusion; Klebsiella pneumoniae isolates from
the patient's blood and platelet bag residuals and a nontransfused platelet unit
were matched using WGS. Investigation revealed no deviations in blood supplier or
hospital procedures. Findings in this report highlight that even when following
current procedures, the risk for transfusion-related infection and fatality
persists, making additional interventions necessary. Clinicians need to be
vigilant in monitoring for platelet-transmitted bacterial infections and report
adverse reactions to blood suppliers and hemovigilance systems. Blood suppliers
and hospitals could consider additional evidence-based bacterial contamination
risk mitigation strategies, including pathogen inactivation, rapid detection
devices, and modified screening of bacterial culture protocols.
PMID- 29953429
TI - Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to
Treat Latent Mycobacterium tuberculosis Infection.
AB - Treatment of latent tuberculosis infection (LTBI) is critical to the control and
elimination of tuberculosis disease (TB) in the United States. In 2011, CDC
recommended a short-course combination regimen of once-weekly isoniazid and
rifapentine for 12 weeks (3HP) by directly observed therapy (DOT) for treatment
of LTBI, with limitations for use in children aged <12 years and persons with
human immunodeficiency virus (HIV) infection (1). CDC identified the use of 3HP
in those populations, as well as self-administration of the 3HP regimen, as areas
to address in updated recommendations. In 2017, a CDC Work Group conducted a
systematic review and meta-analyses of the 3HP regimen using methods adapted from
the Guide to Community Preventive Services. In total, 19 articles representing 15
unique studies were included in the meta-analysis, which determined that 3HP is
as safe and effective as other recommended LTBI regimens and achieves
substantially higher treatment completion rates. In July 2017, the Work Group
presented the meta-analysis findings to a group of TB experts, and in December
2017, CDC solicited input from the Advisory Council for the Elimination of
Tuberculosis (ACET) and members of the public for incorporation into the final
recommendations. CDC continues to recommend 3HP for treatment of LTBI in adults
and now recommends use of 3HP 1) in persons with LTBI aged 2-17 years; 2) in
persons with LTBI who have HIV infection, including acquired immunodeficiency
syndrome (AIDS), and are taking antiretroviral medications with acceptable drug
drug interactions with rifapentine; and 3) by DOT or self-administered therapy
(SAT) in persons aged >=2 years.
PMID- 29953430
TI - Geographic Variation in Pediatric Cancer Incidence - United States, 2003-2014.
AB - Approximately 15,000 persons aged <20 years receive a cancer diagnosis each year
in the United States (1). National surveillance data could provide understanding
of geographic variation in occurrence of new cases to guide public health
planning and investigation (2,3). Past research on pediatric cancer incidence
described differences by U.S. Census region but did not provide state-level
estimates (4). To adequately describe geographic variation in cancer incidence
among persons aged <20 years in the United States, CDC analyzed data from United
States Cancer Statistics (USCS) during 2003-2014 and identified 171,432 cases of
pediatric cancer during this period (incidence = 173.7 cases per 1 million
persons). The cancer types with the highest incidence rates were leukemias
(45.7), brain tumors (30.9), and lymphomas (26.2). By U.S. Census region,
pediatric cancer incidence was highest in the Northeast (188.0) and lowest in the
South (168.0), whereas by state (including the District of Columbia [DC]), rates
were highest in New Hampshire, DC, and New Jersey. Among non-Hispanic whites
(whites) and non-Hispanic blacks (blacks), pediatric cancer incidence was highest
in the Northeast, and the highest rates among Hispanics were in the South. The
highest rates of leukemia were in the West, and the highest rates of lymphoma and
brain tumors were in the Northeast. State-based differences in pediatric cancer
incidence could guide interventions related to accessing care (e.g., in states
with large distances to pediatric oncology centers), clinical trial enrollment,
and state or regional studies designed to further explore variations in cancer
incidence.
PMID- 29953432
TI - Notes from the Field: Domestically Acquired Verona Integron-Mediated Metallo-beta
Lactamase-Producing Enterobacteriaceae - Indiana, 2016-2017.
PMID- 29953431
TI - Surveillance for Certain Health Behaviors and Conditions Among States and
Selected Local Areas - Behavioral Risk Factor Surveillance System, United States,
2015.
AB - PROBLEM: Chronic conditions and disorders (e.g., diabetes, cardiovascular
diseases, arthritis, and depression) are leading causes of morbidity and
mortality in the United States. Healthy behaviors (e.g., physical activity,
avoiding cigarette use, and refraining from binge drinking) and preventive
practices (e.g., visiting a doctor for a routine check-up, tracking blood
pressure, and monitoring blood cholesterol) might help prevent or successfully
manage these chronic conditions. Monitoring chronic diseases, health-risk
behaviors, and access to and use of health care are fundamental to the
development of effective public health programs and policies at the state and
local levels. REPORTING PERIOD: January-December 2015. DESCRIPTION OF THE SYSTEM:
The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing, state
based, random-digit-dialed landline- and cellular-telephone survey of
noninstitutionalized adults aged >=18 years residing in the United States. BRFSS
collects data on health-risk behaviors, chronic diseases and conditions, access
to and use of health care, and use of preventive health services related to the
leading causes of death and disability. This report presents results for all 50
states, the District of Columbia, the Commonwealth of Puerto Rico (Puerto Rico),
and Guam and for 130 metropolitan and micropolitan statistical areas (MMSAs) (N =
441,456 respondents) for 2015. RESULTS: The age-adjusted prevalence estimates of
health-risk behaviors, self-reported chronic health conditions, access to and use
of health care, and use of preventive health services varied substantially by
state, territory, and MMSA in 2015. Results are summarized for selected BRFSS
measures. Each set of proportions refers to the median (range) of age-adjusted
prevalence estimates for health-risk behaviors, self-reported chronic diseases or
conditions, or use of preventive health care services by geographic jurisdiction,
as reported by survey respondents. Adults with good or better health: 84.6%
(65.9%-88.8%) for states and territories and 85.2% (66.9%-91.3%) for MMSAs.
Adults with >=14 days of poor physical health in the past 30 days: 10.9% (8.2%
17.2%) for states and territories and 10.9% (6.6%-19.1%) for MMSAs. Adults with
>=14 days of poor mental health in the past 30 days: 11.3% (7.3%-15.8%) for
states and territories and 11.4% (5.6%-20.5%) for MMSAs. Adults aged 18-64 years
with health care coverage: 86.8% (72.0%-93.8%) for states and territories and
86.8% (63.2%-95.7%) for MMSAs. Adults who received a routine physical checkup
during the preceding 12 months: 69.0% (58.1%-79.8%) for states and territories
and 69.4% (57.1%-81.1%) for MMSAs. Adults who ever had their blood cholesterol
checked: 79.1% (73.3%-86.7%) for states and territories and 79.5% (65.1%-87.3%)
for MMSAs. Current cigarette smoking among adults: 17.7% (9.0%-27.2%) for states
and territories and 17.3% (4.5%-29.5%) for MMSAs. Binge drinking among adults
during the preceding 30 days: 17.2% (11.2%-26.0%) for states and territories and
17.4% (5.5%-24.5%) for MMSAs. Adults who reported no leisure-time physical
activity during the preceding month: 25.5% (17.6%-47.1%) for states and
territories and 24.5% (16.1%-47.3%) for MMSAs. Adults who reported consuming
fruit less than once per day during the preceding month: 40.5% (33.3%-55.5%) for
states and territories and 40.3% (30.1%-57.3%) for MMSAs. Adults who reported
consuming vegetables less than once per day during the preceding month: 22.4%
(16.6%-31.3%) for states and territories and 22.3% (13.6%-32.0%) for MMSAs.
Adults who have obesity: 29.5% (19.9%-36.0%) for states and territories and 28.5%
(17.8%-41.6%) for MMSAs. Adults aged >=45 years with diagnosed diabetes: 15.9%
(11.2%-26.8%) for states and territories and 15.7% (10.5%-27.6%) for MMSAs.
Adults aged >=18 years with a form of arthritis: 22.7% (17.2%-33.6%) for states
and territories and 23.2% (12.3%-33.9%) for MMSAs. Adults having had a depressive
disorder: 19.0% (9.6%-27.0%) for states and territories and 19.2% (9.9%-27.2%)
for MMSAs. Adults with high blood pressure: 29.1% (24.2%-39.9%) for states and
territories and 29.0% (19.7%-41.0%) for MMSAs. Adults with high blood
cholesterol: 31.8% (27.1%-37.3%) for states and territories and 31.4% (23.2%
42.0%) for MMSAs. Adults aged >=45 years who have had coronary heart disease:
10.3% (7.2%-16.8%) for states and territories and 10.1% (4.7%-17.8%) for MMSAs.
Adults aged >=45 years who have had a stroke: 4.9% (2.5%-7.5%) for states and
territories and 4.7% (2.1%-8.4%) for MMSAs. INTERPRETATION: The prevalence of
health care access and use, health-risk behaviors, and chronic health conditions
varied by state, territory, and MMSA. The data in this report underline the
importance of continuing to monitor chronic diseases, health-risk behaviors, and
access to and use of health care in order to assist in the planning and
evaluation of public health programs and policies at the state, territory, and
MMSA level. PUBLIC HEALTH ACTION: State and local health departments and agencies
and others interested in health and health care can continue to use BRFSS data to
identify groups with or at high risk for chronic conditions, unhealthy behaviors,
and limited health care access and use. BRFSS data also can be used to help
design, implement, monitor, and evaluate health-related programs and policies.
PMID- 29953433
TI - QuickStats: Percentage* of Residential Care Communities? That Use Electronic
Health Records,S by Census Region - United States, 2016.
PMID- 29953434
TI - The costs and cost effectiveness of providing second-trimester medical and
surgical safe abortion services in Western Cape Province, South Africa.
AB - BACKGROUND: In South Africa, access to second-trimester abortion services, which
are generally performed using medical induction with misoprostol alone, is
challenging for many women. We aimed to estimate the costs and cost effectiveness
of providing three safe second-trimester abortion services (dilation and
evacuation (D&E)), medical induction with mifepristone and misoprostol (MI
combined), or medical induction with misoprostol alone (MI-misoprostol)) in
Western Cape Province, South Africa to aid policymakers with planning for service
provision in South Africa and similar settings. METHODS: We derived clinical
outcomes data for this economic evaluation from two previously conducted clinical
studies. In 2013-2014, we collected cost data from three public hospitals where
the studies took place. We collected cost data from the health service
perspective through micro-costing activities, including discussions with site
staff. We used decision tree analysis to estimate average costs per patient
interaction (e.g. first visit, procedure visit, etc.), the total average cost per
procedure, and cost-effectiveness in terms of the cost per complete abortion. We
discounted equipment costs at 3%, and present the results in 2015 US dollars.
RESULTS: D&E services were the least costly and the most cost-effective at $91.17
per complete abortion. MI-combined was also less costly and more cost-effective
(at $298.03 per complete abortion) than MI-misoprostol (at $375.31 per complete
abortion), in part due to a shortened inpatient stay. However, an overlap in the
plausible cost ranges for the two medical procedures suggests that the two may
have equivalent costs in some circumstances. CONCLUSION: D&E was most cost
effective in this analysis. However, due to resistance from health care providers
and other barriers, these services are not widely available and scale-up is
challenging. Given South Africa's reliance on medical induction, switching to the
combined regimen could result in greater access to second-trimester services due
to shorter inpatient stays without increasing costs.
PMID- 29953435
TI - Loss of RXFP2 and INSL3 genes in Afrotheria shows that testicular descent is the
ancestral condition in placental mammals.
AB - Descent of testes from a position near the kidneys into the lower abdomen or into
the scrotum is an important developmental process that occurs in all placental
mammals, with the exception of five afrotherian lineages. Since soft-tissue
structures like testes are not preserved in the fossil record and since key parts
of the placental mammal phylogeny remain controversial, it has been debated
whether testicular descent is the ancestral or derived condition in placental
mammals. To resolve this debate, we used genomic data of 71 mammalian species and
analyzed the evolution of two key genes (relaxin/insulin-like family peptide
receptor 2 [RXFP2] and insulin-like 3 [INSL3]) that induce the development of the
gubernaculum, the ligament that is crucial for testicular descent. We show that
both RXFP2 and INSL3 are lost or nonfunctional exclusively in four afrotherians
(tenrec, cape elephant shrew, cape golden mole, and manatee) that completely lack
testicular descent. The presence of remnants of once functional orthologs of both
genes in these afrotherian species shows that these gene losses happened after
the split from the placental mammal ancestor. These "molecular vestiges" provide
strong evidence that testicular descent is the ancestral condition, irrespective
of persisting phylogenetic discrepancies. Furthermore, the absence of shared gene
inactivating mutations and our estimates that the loss of RXFP2 happened at
different time points strongly suggest that testicular descent was lost
independently in Afrotheria. Our results provide a molecular mechanism that
explains the loss of testicular descent in afrotherians and, more generally,
highlight how molecular vestiges can provide insights into the evolution of soft
tissue characters.
PMID- 29953436
TI - Genotyping performance evaluation of commercially available HIV-1 drug resistance
test.
AB - BACKGROUND: ATCC HIV-1 drug resistance test kit was designed to detect HIV-1 drug
resistance (HIVDR) mutations in the protease and reverse transcriptase genes for
all HIV-1 group M subtypes and circulating recombinant forms. The test has been
validated for both plasma and dried blood spot specimen types with viral load
(VL) of >=1000 copies/ml. We performed an in-country assessment on the kit to
determine the genotyping sensitivity and its accuracy in detecting HIVDR
mutations using plasma samples stored under suboptimal conditions. METHODS: Among
572 samples with VL >=1000 copies/ml that had been genotyped by ViroSeq assay,
183 were randomly selected, including 85 successful genotyped and 98 unsuccessful
genotyped samples. They were tested with ATCC kits following the manufacturer's
instructions. Sequence identity and HIVDR patterns were analysed with Stanford
University HIV Drug Resistance HIVdb program. RESULTS: Of the 183 samples, 127
(69.4%) were successfully genotyped by either method. While ViroSeq system
genotyped 85/183 (46.5%) with median VL of 32,971 (IQR: 11,150-96,506) copies/ml,
ATCC genotyped 115/183 (62.8%) samples with median VL of 23,068 (IQR: 7,397
86,086) copies/ml. Of the 98 unsuccessful genotyped samples with ViroSeq assay,
42 (42.9%) samples with lower median VL of 13,906 (IQR: 6,122-72,329) copies/ml
were successfully genotyped using ATCC. Sequence identity analysis revealed that
the sequences generated by both methods were >98% identical and yielded similar
HIVDR profiles at individual patient level. CONCLUSION: This study confirms that
ATCC kit showed greater sensitivity in genotyping plasma samples stored in
suboptimal conditions experiencing frequent and prolonged power outage. Thus, it
is more sensitive particularly for subtypes A and A/G HIV-1 in resource-limited
settings.
PMID- 29953437
TI - Two critical positions in zinc finger domains are heavily mutated in three human
cancer types.
AB - A major goal of cancer genomics is to identify somatic mutations that play a role
in tumor initiation or progression. Somatic mutations within transcription
factors are of particular interest, as gene expression dysregulation is
widespread in cancers. The substantial gene expression variation evident across
tumors suggests that numerous regulatory factors are likely to be involved and
that somatic mutations within them may not occur at high frequencies across
patient cohorts, thereby complicating efforts to uncover which ones are cancer
relevant. Here we analyze somatic mutations within the largest family of human
transcription factors, namely those that bind DNA via Cys2His2 zinc finger
domains. Specifically, to hone in on important mutations within these genes, we
aggregated somatic mutations across all of them by their positions within
Cys2His2 zinc finger domains. Remarkably, we found that for three classes of
cancers profiled by The Cancer Genome Atlas (TCGA)-Uterine Corpus Endometrial
Carcinoma, Colon and Rectal Adenocarcinomas, and Skin Cutaneous Melanoma-two
specific, functionally important positions within zinc finger domains are mutated
significantly more often than expected by chance, with alterations in 18%, 10%
and 43% of tumors, respectively. Numerous zinc finger genes are affected, with
those containing Kruppel-associated box (KRAB) repressor domains preferentially
targeted by these mutations. Further, the genes with these mutations also have
high overall missense mutation rates, are expressed at levels comparable to those
of known cancer genes, and together have biological process annotations that are
consistent with roles in cancers. Altogether, we introduce evidence broadly
implicating mutations within a diverse set of zinc finger proteins as relevant
for cancer, and propose that they contribute to the widespread transcriptional
dysregulation observed in cancer cells.
PMID- 29953438
TI - Dengue virus serotype distribution based on serological evidence in pediatric
urban population in Indonesia.
AB - BACKGROUND: Dengue is a febrile illness transmitted by mosquitoes, causing
disease across the tropical and sub-tropical world. Antibody prevalence data and
serotype distributions describe population-level risk and inform public health
decision-making. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional study we
used data from a pediatric dengue seroprevalence study to describe historical
dengue serotype circulation, according to age and geographic location. A sub
sample of 780 dengue IgG-positive sera, collected from 30 sites across urban
Indonesia in 2014, were tested by the plaque reduction neutralization test (PRNT)
to measure the prevalence and concentration of serotype-specific neutralizing
antibodies according to subject age and geography. PRNT results were obtained
from 776 subjects with mean age of 9.6 years. 765 (98.6%) neutralized one or more
dengue serotype at a threshold of >10 (1/dil). Multitypic profiles were observed
in 50.9% of the samples; a proportion which increased to 63.1% in subjects aged
15-18 years. Amongst monotypic samples, the highest proportion was reactive
against DENV-2, followed by DENV-1, and DENV-3, with some variation across the
country. DENV-4 was the least common serotype. The highest anti-dengue antibody
titers were recorded against DENV-2, and increased with age to a geometric mean
of 516.5 [1/dil] in the oldest age group. CONCLUSIONS/SIGNIFICANCE: We found that
all four dengue serotypes have been widely circulating in most of urban
Indonesia, and more than half of children had already been exposed to >1 dengue
serotype, demonstrating intense transmission often associated with more severe
clinical episodes. These data will help inform policymakers and highlight the
importance of dengue surveillance, prevention and control.
PMID- 29953439
TI - The effect of pegbovigrastim on circulating neutrophil count in dairy cattle: A
randomized controlled trial.
AB - Previous research in various species has shown that granulocyte-colony
stimulating factor stimulates the production and release of neutrophils from bone
marrow. The objective of this study was to characterize the effects of
polyethylene glycol-bound bovine granulocyte colony-stimulating factor
(pegbovigrastim; Imrestor, Elanco) on circulating leukocyte counts. Thirty-four
Holstein cows were randomly assigned to receive 2 injections of either
physiologic saline (n = 16) or pegbovigrastim (n = 18), 7 days before expected
calving (d -7) and within 24 hours after calving (d 0). Cows were sampled at d
7, d -6, d 0, d +1, d +7, and d +21, relative to calving. Only cows for which the
interval from the first injection to calving was >= 4 d and <= 10 d were
included, such that the interval (mean +/- SD) from first treatment to calving
was 6.7 +/- 1.9 d. Treatment effects were assessed with mixed linear regression
models. After the first injection, neutrophil counts (*109/ L) in pegbovigrastim
treated cows increased from 4.3 (95% CI 3.8 to 4.8) at d -7 to 18.2 (CI 16.3 to
20.3) at d -6 (P < 0.0001). Their counts then decreased from d -6 to d 0, when
the second injection was administered, at a rate of -0.31 *109 neutrophils/L/day
(P < 0.0001). After the second injection, neutrophil counts increased from 16.4
(CI 13.7 to 19.6) at d 0 to 32.8 (CI 25.2 to 42.7) at d +1 (P < 0.0001), after
which counts decreased at a rate of -3.73 *109 neutrophils/L/day until d +7 (P <
0.0001). Counts continued to decrease from d +7 to d +21 at a slower rate of
0.43 *109 neutrophils/L/day (P < 0.0001), until baseline levels were reached.
Conversely, in control cows, neutrophil counts were unchanged from d -7 to d -6
(P = 0.86) after the first injection and then decreased from 6.1 (CI 5.0-7.3) at
d 0, to 3.2 (CI 2.4-4.2) at d +1 (P < 0.0001) after the second injection.
Neutrophil count was greater (P < 0.001) in pegbovigrastim-treated than in
control cows at days -6, 0, +1 and +7. Area under the curve (cells *109/ L per 28
d) for neutrophil counts in the pegbovigrastim group was 429, versus 99 in the
control group (P < 0.0001). The response to each injection of pegbovigrastim was
additive and consisted of 95% segmented neutrophils, suggesting that the effect
of the treatment was to release mature neutrophils from a substantial pool
available in the bone marrow. The sustained increase in circulating neutrophil
count around the time of calving may contribute to improved health during the
peripartum transition period.
PMID- 29953440
TI - Evidence of zoonotic leprosy in Para, Brazilian Amazon, and risks associated with
human contact or consumption of armadillos.
AB - Mycobacterium leprae (M. leprae) is a human pathogen and the causative agent for
leprosy, a chronic disease characterized by lesions of the skin and peripheral
nerve damage. Zoonotic transmission of M. leprae to humans by nine-banded
armadillos (Dasypus novemcinctus) has been shown to occur in the southern United
States, mainly in Texas, Louisiana, and Florida. Nine-banded armadillos are also
common in South America, and residents living in some areas in Brazil hunt and
kill armadillos as a dietary source of protein. This study examines the extent of
M. leprae infection in wild armadillos and whether these New World mammals may be
a natural reservoir for leprosy transmission in Brazil, similar to the situation
in the southern states of the U.S. The presence of the M. leprae-specific
repetitive sequence RLEP was detected by PCR amplification in purified DNA
extracted from armadillo spleen and liver tissue samples. A positive RLEP signal
was confirmed in 62% of the armadillos (10/16), indicating high rates of
infection with M. leprae. Immunohistochemistry of sections of infected armadillo
spleens revealed mycobacterial DNA and cell wall constituents in situ detected by
SYBR Gold and auramine/rhodamine staining techniques, respectively. The M. leprae
specific antigen, phenolic glycolipid I (PGL-I) was detected in spleen sections
using a rabbit polyclonal antibody specific for PGL-I. Anti-PGL-I titers were
assessed by ELISA in sera from 146 inhabitants of Belterra, a hyperendemic city
located in western Para state in Brazil. A positive anti-PGL-I titer is a known
biomarker for M. leprae infection in both humans and armadillos. Individuals who
consumed armadillo meat most frequently (more than once per month) showed a
significantly higher anti-PGL-I titer than those who did not eat or ate less
frequently than once per month. Armadillos infected with M. leprae represent a
potential environmental reservoir. Consequently, people who hunt, kill, or
process or eat armadillo meat are at a higher risk for infection with M. leprae
from these animals.
PMID- 29953441
TI - Aerobic exercise and DNA methylation in postmenopausal women: An ancillary
analysis of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA)
Trial.
AB - : Physical activity is associated with a lower risk of breast, colon, and
endometrial cancer. Epigenetic mechanisms such as changes in DNA methylation may
help to explain these protective effects. We assessed the impact of a one year
aerobic exercise intervention on DNA methylation biomarkers believed to play a
role in carcinogenesis. The Alberta Physical Activity and Breast Cancer
Prevention (ALPHA) Trial was a two-armed randomized controlled trial in 320
healthy, inactive, postmenopausal women with no history of cancer. In an
ancillary analysis, frozen blood samples (n = 256) were reassessed for levels of
DNA methylation within LINE-1 and Alu repeats as well as within the promoter
regions of APC, BRCA1, RASSF1, and hTERT genes. Differences between the exercise
and control arm at 12-months, after adjusting for baseline values, were estimated
within an intent-to-treat and per-protocol analysis using linear regression. No
significant differences in DNA methylation between the exercise and control arms
were observed. In an exploratory analysis, we found that the prospective change
in estimated VO2max was negatively associated with RASSF1 methylation in a dose
response manner (p-trend = 0.04). A year-long aerobic exercise intervention does
not affect LINE-1, Alu, APC, BRCA1, RASSF1, or hTERT methylation in healthy,
inactive, postmenopausal women. Changes in DNA methylation within these genomic
regions may not mediate the association between physical activity and cancer in
healthy postmenopausal women. Additional research is needed to validate our
findings with RASSF1 methylation. TRIAL REGISTRATION: ClinicalTrials.gov
NCT00522262.
PMID- 29953442
TI - Testing for alpha-1 antitrypsin in COPD in outpatient respiratory clinics in
Spain: A multilevel, cross-sectional analysis of the EPOCONSUL study.
AB - BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is the most common hereditary
disorder in adults, but is under-recognized. In Spain, the number of patients
diagnosed with AATD is much lower than expected according to epidemiologic
studies. The objectives of this study were to assess the frequency and
determinants of testing serum alpha1-antitrypsin (AAT) levels in COPD patients,
and to describe factors associated with testing. METHODS: EPOCONSUL is a cross
sectional clinical audit, recruiting consecutive COPD cases over one year. The
study evaluated serum AAT level determination in COPD patients and associations
between individual, disease-related, and hospital characteristics. RESULTS: A
total of 4,405 clinical records for COPD patients from 57 Spanish hospitals were
evaluated. Only 995 (22.5%) patients had serum AAT tested on some occasion. A
number of patient characteristics (being male [OR 0.5, p < 0.001], <=55 years old
[OR 2.38, p<0.001], BMI<=21 kg/m2 [OR 1.71, p<0.001], FEV1(%)<50% [OR 1.35,
p<0.001], chronic bronchitis [OR 0.79, p < 0.001], Charlson index >= 3 [OR 0.66,
p < 0.001], or history or symptoms of asthma [OR 1.32, p<0.001]), and management
at a specialized COPD outpatient clinic [OR 2.73,p<0.001] were identified as
factors independently associated with ever testing COPD patients for AATD.
Overall, 114 COPD patients (11.5% of those tested) had AATD. Of them, 26 (22.8%)
patients had severe deficiency. Patients with AATD were younger, with a low pack
year index, and were more likely to have emphysema (p<0.05). CONCLUSION: Testing
of AAT blood levels in COPD patients treated at outpatient respiratory clinics in
Spain is infrequent. However, when tested, AATD (based on the serum AAT levels
<=100 mg/dL) is detected in one in five COPD patients. Efforts to optimize AATD
case detection in COPD are needed.
PMID- 29953443
TI - Contribution of the periosteum to mandibular distraction.
AB - Mandibular distraction is a surgical process that progressively lengthens bone.
To improve the distraction procedure and devices, the load of distraction and the
mechanical strain of soft tissues during the process must be determined. We
tested the assumption that it could be the periosteum primarily opposing
distraction. Therefore we assessed the mechanical properties of the human
mandibular periosteum and compared the stress-strain data with the torque
measured on the activator during a cadaveric mandibular distraction. A 20 mm
horizontal mandibular distraction was performed in 7 cadavers using standard
distractors. Torque was measured with a torquemeter placed on the activation rods
of the devices, providing a load (Lt) for each millimeter of distraction. In
parallel, 18 periosteum samples were harvested from 9 cadaver mandibles. Uniaxial
tensile tests were performed on the specimens and an estimated load (Lc) was
calculated using periosteal stress-strain data and mandibular dimensions. During
the distraction process, we observed an increase of the load Lt from 11.6 to 50.6
N. The periosteum exhibited a nonlinear viscoelastic stress-strain relationship,
typical of biological tissues composed of collagen and elastin. The median Lc and
Lt were not significantly different for the first millimeter of distraction. We
demonstrated the periosteum is primarily responsible for opposing the distraction
load.
PMID- 29953444
TI - Genetic contributions to lupus nephritis in a multi-ethnic cohort of systemic
lupus erythematous patients.
AB - OBJECTIVE: African Americans, East Asians, and Hispanics with systemic lupus
erythematous (SLE) are more likely to develop lupus nephritis (LN) than are SLE
patients of European descent. The etiology of this difference is not clear, and
this study was undertaken to investigate how genetic variants might explain this
effect. METHODS: In this cross-sectional study, 1244 SLE patients from
multiethnic case collections were genotyped for 817,810 single-nucleotide
polymorphisms (SNPs) across the genome. Continental genetic ancestry was
estimated utilizing the program ADMIXTURE. Gene-based testing and pathway
analysis was performed within each ethnic group and meta-analyzed across
ethnicities. We also performed candidate SNP association tests with SNPs
previously established as risk alleles for SLE, LN, and chronic kidney disease
(CKD). Association testing and logistic regression models were performed with LN
as the outcome, adjusted for continental ancestries, sex, disease duration, and
age. RESULTS: We studied 255 North European, 263 South European, 238 Hispanic,
224 African American and 264 East Asian SLE patients, of whom 606 had LN (48.7%).
In genome-wide gene-based and candidate SNP analyses, we found distinct genes,
pathways and established risk SNPs associated with LN for each ethnic group. Gene
based analyses showed significant associations between variation in ZNF546 (p =
1.0E-06), TRIM15 (p = 1.0E-06), and TRIMI0 (p = 1.0E-06) and LN among South
Europeans, and TTC34 (p = 8.0E-06) was significantly associated with LN among
Hispanics. The SNP rs8091180 in NFATC1 was associated with LN (OR 1.43, p = 3.3E
04) in the candidate SNP meta-analysis with the highest OR among African
Americans (OR 2.17, p = 0.0035). CONCLUSION: Distinct genetic factors are
associated with the risk of LN in SLE patients of different ethnicities. CKD risk
alleles may play a role in the development of LN in addition to SLE-associated
risk variants. These findings may further explain the clinical heterogeneity of
LN risk and response to therapy observed between different ethnic groups.
PMID- 29953445
TI - Effects of plant population density and root-induced cytokinin on the corn
compensatory growth during post-drought rewatering.
AB - The effect of plant population density (PPD) and root-induced leaf cytokinin on
the compensatory growth of potted corn seedlings during post-drought rewatering
was investigated. The study design comprised four treatments: (1) wetness with
low PPD, (2) wetness with high PPD, (3) rewatering with low PPD, and (4)
rewatering with high PPD. Results showed that drought stress restrained the
growth of corns. By contrast, rewatering enhanced the net photosynthetic rate and
growth of corns. During the 8 days of rewatering, compensatory growth during post
drought rewatering occurred in corns with high PPD; however, such compensatory
growth did not occur in corns with low PPD. Zeatin riboside concentrations in
leaves and xylem saps were significantly higher under rewatering treatment than
those under wet treatment. High leaf cytokinin concentration accelerated corn
growth. The coefficients of variation and Gini-coefficient of wet treatment were
significantly higher than those of rewatering treatment under high PPD,
demonstrating that intense intraspecific competition occurred in the wet
treatment. Extreme intraspecific competition negatively affected net
photosynthetic rate. In brief, the interactions between root-induced leaf
cytokinin and weak intraspecific competition promoted the compensatory growth
under high PPD.
PMID- 29953447
TI - The nonconscious cessation of affiliative motivation: A replication and extension
study.
AB - Previous research has documented that incidentally processed action-words can
produce corresponding behavior and that affective-motivational processes modulate
these effects. The present study aimed to (1) replicate earlier work showing that
behavioral effects of exposure to social affiliation related action-words (e.g.,
socialize, party, going-out) cease when these action-words are co-activated with
negative stimuli, (2) probe moderation effects of individual differences in the
affiliation motive, and (3) examine whether action-word priming effects on
behavior rely on specific-word associations rather than the activation of a broad
concept. Results of an experimental study (N = 191) showed that exposure-effects
of affiliation related words on behavior instrumental in attaining affiliation
goals cease when these words were co-activated with negative affect, but this
cessation effect was relatively weak and non-significant. Subsequent analyses
revealed that the effect was moderated by the affiliation motive: The cessation
effect mainly occurred for individuals with a strong affiliation motive. Further,
we found no evidence that word priming effects do merely occur via specific-word
associations.
PMID- 29953446
TI - Co-occurrence of opisthorchiasis and diabetes exacerbates morbidity of the
hepatobiliary tract disease.
AB - Complications arising from infection with the carcinogenic liver fluke
Opisthorchis viverrini cause substantial morbidity and mortality in Thailand and
adjacent lower Mekong countries. In parallel, the incidence rate of diabetes
mellitus (DM) is increasing in this same region, and indeed worldwide. Many
residents in opisthorchiasis-endemic regions also exhibit DM, but the
hepatobiliary disease arising during the co-occurrence of these two conditions
remains to be characterized. Here, the histopathological profile during co
occurrence of opisthorchiasis and DM was investigated in a rodent model of human
opisthorchiasis in which diabetes was induced with streptozotocin. The effects of
excretory/secretory products from the liver fluke, O. viverrini (OVES) on
hepatocyte and cholangiocyte responses during hyperglycemic conditions also were
monitored. Both the liver fluke-infected hamsters (OV group) and hamsters with DM
lost weight compared to control hamsters. Weight loss was even more marked in the
hamsters with both opisthorchiasis and DM (OD group). Hypertrophy of hepatocytes,
altered biliary canaliculi, and biliary hyperplasia were more prominent in the OD
group, compared with OV and DM groups. Profound oxidative DNA damage, evidenced
by 8-oxo-2'-deoxyguanosine, proliferating cell nuclear antigen, and periductal
fibrosis characterized the OD compared to OV and DM hamsters. Upregulation of
expression of cytokines in response to infection and impairment of the pathway
for insulin receptor substrate (IRS)/phosphatidylinositol-3-kinases
(PI3K)/protein kinase B (AKT) signaling attended these changes. In vitro, OVES
and glucose provoked time- and dose-dependent effects on the proliferation of
both hepatocytes and cholangiocytes. In overview, the co-occurrence of
opisthorchiasis and diabetes exacerbated pathophysiological damage to the
hepatobiliary tract. We speculate that opisthorchiasis and diabetes together
aggravate hepatobiliary pathogenesis through an IRS/PI3K/AKT-independent pathway.
PMID- 29953448
TI - Fast sequence analysis based on diamond sampling.
AB - Both in DNA and protein contexts, an important method for modelling motifs is to
utilize position weight matrix (PWM) in biological sequences. With the
development of genome sequencing technology, the quantity of the sequence data is
increasing explosively, so the faster searching algorithms which have the ability
to meet the increasingly need are desired to develop. In this paper, we proposed
a method for speeding up the searching process of candidate transcription factor
binding sites (TFBS), and the users can be allowed to specify p threshold to get
the desired trade-off between speed and sensitivity for a particular sequence
analysis. Moreover, the proposed method can also be generalized to large-scale
annotation and sequence projects.
PMID- 29953449
TI - Within-patient mutation frequencies reveal fitness costs of CpG dinucleotides and
drastic amino acid changes in HIV.
AB - HIV has a high mutation rate, which contributes to its ability to evolve quickly.
However, we know little about the fitness costs of individual HIV mutations in
vivo, their distribution and the different factors shaping the viral fitness
landscape. We calculated the mean frequency of transition mutations at 870 sites
of the pol gene in 160 patients, allowing us to determine the cost of these
mutations. As expected, we found high costs for non-synonymous and nonsense
mutations as compared to synonymous mutations. In addition, we found that non
synonymous mutations that lead to drastic amino acid changes are twice as costly
as those that do not and mutations that create new CpG dinucleotides are also
twice as costly as those that do not. We also found that G->A and C->T mutations
are more costly than A->G mutations. We anticipate that our new in vivo frequency
based approach will provide insights into the fitness landscape and evolvability
of not only HIV, but a variety of microbes.
PMID- 29953450
TI - High-throughput image-based monitoring of cell aggregation and microspheroid
formation.
AB - Studies on monolayer cultures and whole-animal models for the prediction of the
response of native human tissue are associated with limitations. Therefore, more
and more laboratories are tending towards multicellular spheroids grown in vitro
as a model of native tissues. In addition, they are increasingly used in a wide
range of biofabrication methodologies. These 3D microspheroids are generated
through a self-assembly process that is still poorly characterised, called
cellular aggregation. Here, a system is proposed for the automated, non-invasive
and high throughput monitoring of the morphological changes during cell
aggregation. Microwell patterned inserts were used for spheroid formation while
an automated microscope with 4x bright-field objective captured the morphological
changes during this process. Subsequently, the acquired time-lapse images were
automatically segmented and several morphological features such as minor axis
length, major axis length, roundness, area, perimeter and circularity were
extracted for each spheroid. The method was quantitatively validated with respect
to manual segmentation on four sets of +/- 60 spheroids. The average
sensitivities and precisions of the proposed segmentation method ranged from
96.67-97.84% and 96.77-97.73%, respectively. In addition, the different
morphological features were validated, obtaining average relative errors between
0.78-4.50%. On average, a spheroid was processed 73 times faster than a human
operator. As opposed to existing algorithms, our methodology was not only able to
automatically monitor compact spheroids but also the aggregation process of
individual spheroids, and this in an accurate and high-throughput manner. In
total, the aggregation behaviour of more than 700 individual spheroids was
monitored over a duration of 16 hours with a time interval of 5 minutes, and this
could be increased up to 48,000 for the described culture format. In conclusion,
the proposed system has the potential to be used for unravelling the mechanisms
involved in spheroid formation and monitoring their formation during large-scale
manufacturing protocols.
PMID- 29953451
TI - Alarming rates of antimicrobial resistance and fungal sepsis in outborn neonates
in North India.
AB - BACKGROUND: There is a paucity of data on the epidemiology of sepsis in outborn
neonates being referred to level-3 units in low- and middle-income countries
(LMIC). The objective of the present study was to evaluate the prevalence of
sepsis and outcomes of outborn neonates with sepsis, and to characterize the
pathogen profile and antimicrobial resistance (AMR) patterns of common isolates
in them. METHODS: In this prospective observational cohort study (2011-2015), a
dedicated research team enrolled all neonates admitted to an outborn level-3
neonatal unit and followed them until discharge/death. Sepsis work-up including
blood culture(s) was performed upon suspicion of sepsis. All the isolates were
identified and tested for antimicrobial susceptibility. Gram-negative pathogens
resistant to any three of the five antibiotic classes (extended-spectrum
cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin
tazobactam) were labeled multi-drug resistant. RESULTS: Of the total of 2588
neonates enrolled, culture positive sepsis and total sepsis-i.e. culture positive
and/or culture negative sepsis-was diagnosed in 13.1% (95% CI 11.8% to 14.5%) and
54.7% (95% CI 52.8% to 56.6%), respectively. The case fatality rates were 23.4%
and 11.0% in culture-positive and total sepsis, respectively. Sepsis accounted
for two-thirds of total neonatal deaths (153/235, 63.0%). Bacterial isolates
caused about three-fourths (296/401; 73.8%) of the infections. The two common
pathogens-Klebsiella pneumoniae (n = 50, 12.5%) and Acinetobacter baumannii (n =
46, 11.5%)-showed high degree of multi-drug resistance (78.0% and 91.3%,
respectively) and carbapenem resistance (84.0% and 91.3%, respectively). About a
quarter of infections were caused by Candida spp. (n = 91; 22.7%); almost three
fourths (73.7%) of these infections occurred in neonates born at or after 32
weeks' gestation and about two-thirds (62.1%) in those weighing 1500 g or more at
birth. CONCLUSIONS: In this large outborn cohort, we report high burden of
sepsis, high prevalence of systemic fungal infections, and alarming rates of
antimicrobial resistance among bacterial pathogens.
PMID- 29953452
TI - Spatial distribution patterns of soil mite communities and their relationships
with edaphic factors in a 30-year tillage cornfield in northeast China.
AB - Spatial distribution is an important topic in community ecology and a key to
understanding the structure and dynamics of populations and communities. However,
the available information related to the spatial patterns of soil mite
communities in long-term tillage agroecosystems remains insufficient. In this
study, we examined the spatial patterns of soil mite communities to explain the
spatial relationships between soil mite communities and soil parameters. Soil
fauna were sampled three times (August, September and October 2015) at 121
locations arranged regularly within a 400 m * 400 m monitoring plot.
Additionally, we estimated the physical and chemical parameters of the same
sampling locations. The distribution patterns of the soil mite community and the
edaphic parameters were analyzed using a range of geostatistical tools. Moran's I
coefficient showed that, during each sampling period, the total abundance of the
soil mite communities and the abundance of the dominant mite populations were
spatially autocorrelated. The soil mite communities demonstrated clear patchy
distribution patterns within the study plot. These patterns were sampling period
specific. Cross-semivariograms showed both negative and positive cross
correlations between soil mite communities and environmental factors. Mantel
tests showed a significant and positive relationship between soil mite community
and soil organic matter and soil pH only in August. This study demonstrated that
in the cornfield, the soil mite distribution exhibited strong or moderate spatial
dependence, and the mites formed patches with sizes less than one hundred meters.
In addition, in this long-term tillage agroecosystem, soil factors had less
influence on the observed pattern of soil mite communities. Further experiments
that take into account human activity and spatial factors should be performed to
study the factors that drive the spatial distribution of soil microarthropods.
PMID- 29953453
TI - A speed-fidelity trade-off determines the mutation rate and virulence of an RNA
virus.
AB - Mutation rates can evolve through genetic drift, indirect selection due to
genetic hitchhiking, or direct selection on the physicochemical cost of high
fidelity. However, for many systems, it has been difficult to disentangle the
relative impact of these forces empirically. In RNA viruses, an observed
correlation between mutation rate and virulence has led many to argue that their
extremely high mutation rates are advantageous because they may allow for
increased adaptability. This argument has profound implications because it
suggests that pathogenesis in many viral infections depends on rare or de novo
mutations. Here, we present data for an alternative model whereby RNA viruses
evolve high mutation rates as a byproduct of selection for increased replicative
speed. We find that a poliovirus antimutator, 3DG64S, has a significant
replication defect and that wild-type (WT) and 3DG64S populations have similar
adaptability in 2 distinct cellular environments. Experimental evolution of
3DG64S under selection for replicative speed led to reversion and compensation of
the fidelity phenotype. Mice infected with 3DG64S exhibited delayed morbidity at
doses well above the lethal level, consistent with attenuation by slower growth
as opposed to reduced mutational supply. Furthermore, compensation of the 3DG64S
growth defect restored virulence, while compensation of the fidelity phenotype
did not. Our data are consistent with the kinetic proofreading model for
biosynthetic reactions and suggest that speed is more important than accuracy. In
contrast with what has been suggested for many RNA viruses, we find that within
host spread is associated with viral replicative speed and not standing genetic
diversity.
PMID- 29953454
TI - Schistosomiasis in Africa: Improving strategies for long-term and sustainable
morbidity control.
PMID- 29953455
TI - Mean arterial pressure targeted fluid resuscitation may lead to fluid overload: A
bleeding-resuscitation animal experiment.
AB - INTRODUCTION: Fluid resuscitation is the cornerstone of treatment in hemorrhagic
shock. Despite increasing doubts, several guidelines recommend to maintain mean
arterial pressure (MAP) >65 mmHg as the most frequent indication of fluid
therapy. Our aim was to investigate the effects of a MAP-guided management in a
bleeding-resuscitation animal experiment. MATERIALS AND METHODS: After anesthesia
and instrumentation (tbsl) animals were bled till the initial stroke volume index
dropped by 50% (t0). Fluid replacement was performed in 4 equivalent steps (t1-4)
with balanced crystalloid solution to reach the baseline values of MAP. Invasive
hemodynamic measurements and blood gas analyses were performed after each step.
RESULTS: Mean arterial pressure dropped from tbsl to t0 (114+/-11 vs 76.9+/-16.9
mmHg, p<0.001) and returned to baseline by t4 (101.4+/-14.4 mmHg). From tbsl-t0
stroke volume index (SVI), cardiac index (CI) decreased (SVI: 40+/-8.6 vs 19.3+/
3.6 ml/m2, p<0.001; CI: 3.4+/-0.3 vs 1.9+/-0.3 l/min/m2, p<0.001), pulse pressure
variation (PPV) increased (13.2+/-4.3 vs 22.1+/-4.3%, p<0.001). There was a
decrease in oxygen delivery (464+/-45 vs 246+/-26.9 ml/min, p<0.001), central
venous oxygen saturation (82.8+/-5.4 vs 53.6+/-12.1%, p<0.001) and increase in
lactate levels (1.6+/-0.4 vs 3.5+/-1.6 mmol/l, p<0.005). SVI, CI and PPV returned
to their initial values by t2. To normalize MAP fluid therapy had to be continued
till t4, with the total infused volume of 4.5+/-0.8 l. CONCLUSION: In the current
experiment bleeding led to hemorrhagic shock, while MAP remained higher than 65
mmHg. Furthermore, MAP was unable to indicate the normalization of SVI, CI and
PPV that resulted in unnecessary fluid administration. Our data give further
evidence that MAP may be an inappropriate parameter to follow during fluid
resuscitation.
PMID- 29953457
TI - Household food insecurity access scale and dietary diversity score as a proxy
indicator of nutritional status among people living with HIV/AIDS, Bahir Dar,
Ethiopia, 2017.
AB - BACKGROUND: Both household food insecurity and household dietary diversity have
been found reliable in describing the dietary intake of a population. However, it
had not been proven as reliable instrument for assessing nutritional status of
individuals in a clinical context. There has been a need for evidence on the
validity of using proxy and easy dietary indicators for nutritional status.
METHOD: A facility based cross sectional study design was employed on 423 people
with HIV infection visiting all ART clinics in Bahir Dar, North Ethiopia.
Nutritional status was determined by computing BMI. Food insecurity was assessed
using household food insecurity access scale. Dietary diversity was measured
using a tool adopted from Food and Nutrition Technical Assistance Project. Data
were entered to Epidata version 3.1and analyzed by SPSS version 20. Reliability
analysis, sensitivity and specificity analysis were determined. RESULT: The
sensitivity of the household food insecurity access scale and dietary diversity
score was 87.9% and 79.8%, respectively, while their specificity was 56.2% and
70.2%. The AUC at 95% CI for the household food insecurity access scale and
household dietary diversity score were 73.4 (68.4-78.4) and 73.1 (68.1-78.2)
while their cut of point that maximized their sensitivity and specificity was 1
and 6 respectively. Household food insecurity access scale and household dietary
diversity score were found to be reliable tools with a Cronbach's Alpha of 0.926
and 0.799, respectively. CONCLUSION: In assessing under nutrition among PLHIV
especially in limited resource settings, both the household food insecurity
access scale and household dietary diversity score were found valid and reliable
proxy indicators for measuring nutritional status.
PMID- 29953456
TI - Examining the Triple Code Model in numerical cognition: An fMRI study.
AB - The Triple Code Model (TCM) of numerical cognition argues for the existence of
three representational codes for number: Arabic digits, verbal number words, and
analog nonsymbolic magnitude representations, each subserved by functionally
dissociated neural substrates. Despite the popularity of the TCM, no study to
date has explored all three numerical codes within one fMRI paradigm. We
administered three tasks, associated with each of the aforementioned numerical
codes, in order to explore the neural correlates of numerosity processing in a
sample of adults (N = 46). Independent task-control contrast analyses revealed
task-dependent activity in partial support of the model, but also highlight the
inherent complexity of a distributed and overlapping fronto-parietal network
involved in all numerical codes. The results indicate that the TCM correctly
predicts the existence of some functionally dissociated neural substrates, but
requires an update that accounts for interactions with attentional processes.
Parametric contrasts corresponding to differences in task difficulty revealed
specific neural correlates of the distance effect, where closely spaced numbers
become more difficult to discriminate than numbers spaced further apart. A
conjunction analysis illustrated overlapping neural correlates across all tasks,
in line with recent proposals for a fronto-parietal network of number processing.
We additionally provide tentative results suggesting the involvement of format
independent numerosity-sensitive retinotopic maps in the early visual stream,
extending previous findings of nonsymbolic stimulus selectivity. We discuss the
functional roles of the components associated with the model, as well as the
purported fronto-parietal network, and offer arguments in favor of revising the
TCM.
PMID- 29953458
TI - Feasibility, benefit and risk of systematic intraoperative cholangiogram in
patients undergoing emergency cholecystectomy.
AB - BACKGROUND: The role of intraoperative cholangiogram (IOC) during cholecystectomy
is debated. The aim of the present study was to evaluate the feasibility, benefit
and risk of performing systematic IOC in patients undergoing cholecystectomy for
acute gallstone-related disease. METHODS: Between July 2013 and January 2015, all
patients admitted for an acute gallstone-related condition and undergoing same
hospital-stay cholecystectomy were prospectively followed. IOC was systematically
attempted and predictors of IOC failure were analyzed. RESULTS: Among the 581
enrolled patients, IOC was deliberately not performed in 3 cases. IOC was
successful in 509/578 patients (88.1%). The main predictors of IOC failure were
age, body mass index, male gender and associated acute cholecystitis. Thirty-two
patients with suspected common bile duct stone on IOC underwent 38 unnecessary
negative postoperative common bile duct investigations (32/509, 6.3%). There was
one IOC-related adverse outcome (mild pancreatitis, 1/578, 0.2%). CONCLUSIONS:
IOC can be successfully and safely performed in the majority of patients
undergoing cholecystectomy for acute gallstone-related disease. Although its
positive predictive value is suboptimal and results in a number of unnecessary
postoperative common bile duct investigations, IOC accurately rules out common
bile duct stones in patients with acute gallstone-related conditions.
PMID- 29953459
TI - Effectiveness of navigator-based prospective motion correction in MPRAGE data
acquired at 3T.
AB - In MRI, subject motion results in image artifacts. High-resolution 3D scans, like
MPRAGE, are particularly susceptible to motion because of long scan times and
acquisition of data over multiple-shots. Such motion related artifacts have been
shown to cause a bias in cortical measures extracted from segmentation of high
resolution MPRAGE images. Prospective motion correction (PMC) techniques have
been developed to help mitigate artifacts due to subject motion. In this work,
high-resolution MPRAGE images are acquired during intentional head motion to
evaluate the effectiveness of navigator-based PMC techniques to improve both the
accuracy and reproducibility of cortical morphometry measures obtained from image
segmentation. The contribution of reacquiring segments of k-space affected by
motion to the overall performance of PMC is assessed. Additionally, the effect of
subject motion on subcortical structure volumes is investigated. In the presence
of head motion, navigator-based PMC is shown to improve both the accuracy and
reproducibility of cortical and subcortical measures. It is shown that
reacquiring segments of k-space data that are corrupted by motion is an essential
part of navigator-based PMC performance. Subcortical structure volumes are not
affected by motion in the same way as cortical measures; there is not a
consistent underestimation.
PMID- 29953461
TI - A comparison of survivourship and function (grazing and behaviour) of three
gastropod species used as clean-up crew for the marine aquarium trade.
AB - Several million gastropods are collected each year for the marine ornamental
trade to graze on algae detrimental to aquarium species, however, little is known
about popular species' suitability to perform this clean-up crew role. Three
commonly traded gastropods, Turbo bruneus, Tectus fenestratus, and Tegula eiseni
were assessed on their performance. Their survival was quantified as was their
movement, and positioning with respect to water level and growth rates were
calculated from the start and end weights. Nitrocellulose-coated slides were
impregnated with an algal extract and the amount of grazing by each species was
also compared. After 53 days final mortality levels of species were significantly
different with all T. bruneus individuals surviving, whilst all T. fenestratus
individuals apart from two and 35% of the T. eiseni had died by the end of the
experiment. T. bruneus grazed significantly more than individuals of T. eiseni,
and T. fenestratus. Both T. bruneus and T. eiseni were heavier after one month
with T. bruneus gaining significantly more weight than T. eiseni. Greater
percentages of algae were grazed by T. bruneus of increasing weight, although
this relationship was not found for T. eiseni and T. fenestratus. All three
species were generally active and remained within the water for the vast majority
of time, although a small, but significant amount of time was spent out of the
water for T. eiseni. T. fenestratus were significantly less active than T.
bruneus, although the mean activity of T. eiseni was not significantly different
from either species. T. bruneus out performs the other two species as a cleaning
organism especially in the context of fluctuating water quality, thus
highlighting the varying suitability of organisms for this task. Preference in
the ornamental trade should be given to T. bruneus over the other topshells, but
accurate species identification is critical.
PMID- 29953460
TI - Safety of ibuprofen in infants younger than six months: A retrospective cohort
study.
AB - OBJECTIVE: We hypothesized (1) that gastrointestinal (GI) and renal adverse
events (AE) would occur more often in infants first prescribed ibuprofen before
rather than after six months of age and (2) that ibuprofen would be associated
with more adverse effects than acetaminophen in infants younger than six months.
METHODS: We created two partly overlapping retrospective cohorts of infants aged
less than six months when California Medicaid first paid for ibuprofen or
acetaminophen between 2004 and 2010. In the first cohort we compared the
incidence rate ratio (RR) of GI and renal AE between those infants first
prescribed ibuprofen before six months of age with those first prescribed
ibuprofen after six months of age. In the second cohort we compared the RR of GI
and renal AE between infants younger than six months prescribed ibuprofen (+/
acetaminophen) with those prescribed only acetaminophen. RESULTS: We identified
41,669 prescriptions for ibuprofen and 176,991 prescriptions for acetaminophen in
180,333 eligible infants (median age 2.1 months). We did not observe higher RR of
any AE in infants first prescribed ibuprofen before rather than after six months
of age. Most infants prescribed ibuprofen were also prescribed acetaminophen. Any
GI (adjusted (a)RR 1.25, 95% CI 1.13-1.38) and moderate or severe GI AE (aRR
1.24, 95% CI 1.09-1.40) were more common in infants younger than six months who
were prescribed ibuprofen versus acetaminophen alone. Severe GI (aRR 0.63, 95% CI
0.27-1.45) and renal AE (aRR 1.84 95% CI 0.66-5.19) were not different between
the ibuprofen (+/-acetaminophen) and acetaminophen-only groups. CONCLUSIONS: GI
and renal AEs were not higher in infants younger than six months who were
prescribed ibuprofen compared with those aged six to 12 months. AEs were
increased in infants younger than six months who were prescribed ibuprofen
compared with infants who were prescribed acetaminophen alone.
PMID- 29953462
TI - Effect of long-term tillage on soil aggregates and aggregate-associated carbon in
black soil of Northeast China.
AB - Soil tillage can affect the stability and formation of soil aggregates by
disrupting soil structure. Frequent tillage deteriorates soil structure and
weakens soil aggregates, causing them to be susceptible to decay. Different types
of tillage systems affect soil physical properties and organic matter content, in
turn influencing the formation of aggregates. The objective of this study was to
evaluate the effect of long-term tillage on soil aggregates and aggregate
associated carbon in a black soil of Northeast China and to identify the optimal
conservation tillage in this system. This research was conducted on a long-term
tillage experimental field established in 1983 at the Jilin Academy of
Agricultural Sciences, Gongzhuling, China. Plots were treated with four tillage
systems including no tillage (NT), spacing tillage (ST), moldboard plowing (MP),
and conventional tillage (CT). We took samples every 10cm from 0-60cm depth and
demonstrated that water-stable soil aggregates >0.25mm in diameter accounted for
over 66.0% of total aggregates for all tillage treatments, and the percentage for
the ST treatment was 34.5% higher than in the other treatments. The NT treatment
had the highest effect at 0-10cm depth, while the effect for the ST treatment was
highest at 0-30cm. SOC storage decreased with soil depth, with a significant
accumulation at 0-20cm depth. Across treatments, aggregate-associated C at a
depth of 0-10cm was higher in the NT and ST treatments than in the MP and CT
treatments. The advantage of the NT treatment weakened with soil depth, while the
amount of aggregate-associated C remained higher for the ST treatment. There were
more macro-aggregates in the ST and NT treatments than in the MP and CT
treatments, while the MP and CT treatments had more micro-aggregates. The sum of
macro-aggregate contributing rates for soil organic C (SOC) was significantly
superior to that of the micro-aggregates. Water-stable aggregates increased by
34.5% in the ST treatment, effectively improving the soil structure. Furthermore,
0.25-1.00 and 1-2mm aggregates had the highest SOC storage and responded rapidly
to the various tillage treatments. Hence, they can serve as indicators for the
long-term influence of different tillage treatments on the distribution of
aggregates and SOC.
PMID- 29953463
TI - Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic
prescription in infants-A community-based randomized intervention.
AB - BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials
that, until recently, were found in a wide variety of household and personal wash
products. Popular with consumers, TCs have not been shown to protect against
infectious diseases. OBJECTIVES: To determine whether use of TC-containing wash
products reduces incidence of infection in children less than one year of age.
METHODS: Starting in 2011, we nested a randomized intervention of wash products
with and without TCs within a multiethnic birth cohort. Maternal reports of
infectious disease symptoms and antibiotic use were collected weekly by automated
survey; household visits occurred every four months. Antibiotic prescriptions
were identified by medical chart review. Urinary triclosan levels were measured
in a participant subset. Differences by intervention group in reported infectious
disease (primary outcome) and antibiotic use (secondary outcome) were assessed
using mixed effects logistic regression and Fisher's Exact tests, respectively.
RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory
illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC
exposed babies, infectious disease reports did not differ in frequency between
groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic
prescriptions were less common in the TC group than in the non-TC group (7.8% vs.
16.6%, respectively; p = 0.02). CONCLUSIONS: Although randomization to TC
containing wash products was not associated with decreased infectious disease
reports by mothers, TCs were associated with decreased antibiotic prescriptions,
suggesting a benefit against bacterial infection. The recent removal of TCs from
consumer wash products makes further elucidation of benefits and risks
impracticable.
PMID- 29953464
TI - Risk factors for mortality in patients with acute leukemia and bloodstream
infections in the era of multiresistance.
AB - OBJECTIVES: We assess the epidemiology and risk factors for mortality of
bloodstream infection (BSI) in patients with acute leukemia (AL). METHODS:
Prospectively collected data of a cohort study from July 2004 to February 2016.
Multivariate analyses were performed. RESULTS: 589 episodes of BSI were
documented in 357 AL patients, 55% caused by gram-positive bacteria (coagulase
negative staphylococci 35.7%, Enterococcus spp 10.8%) and 43.5% by gram-negative
bacteria (E. coli 21%, PA 12%). We identified 110 (18.7%) multidrug-resistant
(MDR) microorganisms, especially MDR-Pseudomonas aeruginosa (7%) and extended
spectrum beta-lactamase producing Enterobacteriaceae (7%). The 30-day mortality
was 14.8%. Age (OR 3.1; 95% CI 1.7-5.7); chronic lung disease (4.8; 1.1-21.8);
fatal prognosis according to McCabe index (13.9; 6.4-30.3); shock (3.8; 1.9-7.7);
pulmonary infection (3.6; 1.3-9.9); and MDR-PA infections with inappropriate
treatment (12.8; 4.1-40.5) were related to mortality. MDR-PA BSI was associated
to prior antipseudomonal cephalosporin use (9.31; 4.38-19.79); current use of
betalactams (2.01; 1.01-4.3); shock (2.63; 1.03-6.7) and pulmonary source of
infection (9.6; 3.4-27.21). CONCLUSIONS: MDR organisms were commonly isolated in
BSI in AL. Inappropriate empiric antibiotic treatment for MDR-PA is the primary
factor related to mortality that can be changed. New treatment strategies to
improve the coverage of MDR-PA BSI should be considered in those patients with
risk factors for this infection.
PMID- 29953465
TI - Reduced T wave alternans in heart failure responders to cardiac resynchronization
therapy: Evidence of electrical remodeling.
AB - BACKGROUND: T-wave alternans (TWA), a marker of electrical instability, can be
modulated by cardiac resynchronization therapy (CRT). The relationship between
TWA and heart failure response to CRT has not been clearly defined. METHODS AND
RESULTS: In 40-patients (age 65+/-11 years, left ventricular ejection-fraction
[LVEF] 23+/-7%), TWA was evaluated prospectively at median of 2 months (baseline)
and 8 months (follow-up) post-CRT implant. TWA-magnitude (Valt >0MUV, k>=3), its
duration (d), and burden (Valt .d) were quantified in moving 128-beat segments
during incremental atrial (AAI, native-TWA) and atrio-biventricular (DDD-CRT)
pacing. The immediate and long-term effect of CRT on TWA was examined. Clinical
response to CRT was defined as an increase in LVEF of >=5%. Native-TWA was
clinically significant (Valt >=1.9MUV, k>=3) in 68% of subjects at baseline.
Compared to native-TWA at baseline, DDD-CRT pacing at baseline and follow-up
reduced the number of positive TWA segments, peak-magnitude, longest-duration and
peak-burden of TWA (44+/-5 to 33+/-5 to 28+/-4%, p = 0.02 and 0.002; 5.9+/-0.8 to
4.1+/-0.7 to 3.8+/-0.7MUV, p = 0.01 and 0.01; 97+/-9 to 76+/-8 to 67+/-8sec, p =
0.004 and <0.001; and 334+/-65 to 178+/-58 to 146+/-54MUV.sec, p = 0.01 and
0.004). In addition, the number of positive segments and longest-duration of
native-TWA diminished during follow-up (44+/-5 to 35+/-6%, p = 0.044; and 97+/-9
to 81+/-9sec, p = 0.02). Clinical response to CRT was observed in 71% of
patients; the reduction in DDD-CRT paced TWA both at baseline and follow-up was
present only in responders (interaction p-values <0.1). CONCLUSION: Long-term CRT
reduces the prevalence and magnitude of TWA. This CRT induced beneficial
electrical remodeling is a marker of clinical response after CRT.
PMID- 29953466
TI - Genome wide association study for gray leaf spot resistance in tropical maize
core.
AB - Gray leaf spot is a maize foliar disease with worldwide distribution and can
drastically reduce the production in susceptible genotypes. Published works
indicate that resistance to gray leaf spot is a complex trait controlled by
multiple genes, with additive effect and influenced by environment. The aim of
this study was to identify genomic regions, including putative genes, associated
with resistance to gray leaf spot under natural conditions of disease occurrence.
A genome wide association study was conducted with 355,972 single nucleotide
polymorphism markers on a phenotypic data composed by 157 tropical maize inbred
lines, evaluated at Maringa -Brazil. Seven single nucleotide polymorphisms were
significantly associated with gray leaf spot, some of which were localized to
previously reported quantitative trait loci regions. Three gene models linked to
the associated single nucleotide polymorphism were expressed at flowering time
and tissue related with gray leaf spot infection, explaining a considerable
proportion of the phenotypic variance, ranging from 0.34 to 0.38. The gene model
GRMZM2G073465 (bin 10.07) encodes a cysteine protease3 protein, gene model
GRMZM2G007188 (bin 1.02) expresses a rybosylation factor-like protein and the
gene model GRMZM2G476902 (bin 4.08) encodes an armadillo repeat protein. These
three proteins are related with plant defense pathway. Once these genes are
validated in next studies, they will be useful for marker-assisted selection and
can help improve the understanding of maize resistance to gray leaf spot.
PMID- 29953467
TI - The role of phenolic OH groups of flavonoid compounds with H-bond formation
ability to suppress amyloid mature fibrils by destabilizing beta-sheet
conformation of monomeric Abeta17-42.
AB - Alzheimer's disease (AD) is a kind of brain disease that arises due to the
aggregation and fibrillation of amyloid beta-peptides (Abeta). The peptide
Abeta17-42 forms U-shape protofilaments of amyloid mature fibrils by cross-beta
strands, detected in brain cells of individuals with AD. Targeting the structure
of Abeta17-42 and destabilizing its beta-strands by natural compounds could be
effective in the treatment of AD patients. Therefore, the interaction features of
monomeric U-shape Abeta17-42 with natural flavonoids including myricetin, morin
and flavone at different mole ratios were comprehensively studied to recognize
the mechanism of Abeta monomer instability using molecular dynamics (MD)
simulations. We found that all flavonoids have tendency to interact and
destabilize Abeta peptide structure with mole ratio-dependent effects. The
interaction free energies of myricetin (with 6 OHs) and morin (with 5 OHs) were
more negative compared to flavone, although the total binding energies of all
flavonoids are favorable and negative. Myricetin, morin and flavone penetrated
into the core of the Abeta17-42 and formed self-clusters of Abeta17-42-flavonoid
complexes. Analysis of Abeta17-42-flavonoids interactions identified that the
hydrophobic interactions related to SASA-dependent energy are weak in all
complexes. However, the intermolecular H-bonds are a main binding factor for
shifting U-shape rod-like state of Abeta17-42 to globular-like disordered state.
Myricetin and morin polyphenols form H-bonds with both peptide's carbonyl and
amine groups whereas flavone makes H-bonds only with amine substitution. As a
result, polyphenols are more efficient in destabilizing beta-sheet structures of
peptide. Accordingly, the natural polyphenolic flavonoids are useful in forming
stable Abeta17-42-flavonoid clusters to inhibit Abeta17-42 aggregation and these
compounds could be an effective candidate for therapeutically targeting U-shape
protofilaments' monomer in amyloid mature fibrils.
PMID- 29953468
TI - Contact prediction is hardest for the most informative contacts, but improves
with the incorporation of contact potentials.
AB - Co-evolution between pairs of residues in a multiple sequence alignment (MSA) of
homologous proteins has long been proposed as an indicator of structural
contacts. Recently, several methods, such as direct-coupling analysis (DCA) and
MetaPSICOV, have been shown to achieve impressive rates of contact prediction by
taking advantage of considerable sequence data. In this paper, we show that
prediction success rates are highly sensitive to the structural definition of a
contact, with more permissive definitions (i.e., those classifying more pairs as
true contacts) naturally leading to higher positive predictive rates, but at the
expense of the amount of structural information contributed by each contact.
Thus, the remaining limitations of contact prediction algorithms are most
noticeable in conjunction with geometrically restrictive contacts-precisely those
that contribute more information in structure prediction. We suggest that to
improve prediction rates for such "informative" contacts one could combine co
evolution scores with additional indicators of contact likelihood. Specifically,
we find that when a pair of co-varying positions in an MSA is occupied by residue
pairs with favorable statistical contact energies, that pair is more likely to
represent a true contact. We show that combining a contact potential metric with
DCA or MetaPSICOV performs considerably better than DCA or MetaPSICOV alone,
respectively. This is true regardless of contact definition, but especially true
for stricter and more informative contact definitions. In summary, this work
outlines some remaining challenges to be addressed in contact prediction and
proposes and validates a promising direction towards improvement.
PMID- 29953469
TI - The skull of the gerrhonotine lizard Elgaria panamintina (Squamata: Anguidae).
AB - We provide the first description of the skull, osteoderms, and hyoid apparatus of
the poorly known alligator lizard Elgaria panamintina, and compare the cranial
osteology of that species to the widespread and well-studied taxon Elgaria
multicarinata. Patterns of morphological variation resulting from ontogenetic
transformations and pathology are discussed. We employed x-ray computed
tomography (CT) scans to examine two adult specimens of Elgaria panamintina and
two adult specimens of Elgaria multicarinata, in addition to examining multiple
traditionally prepared skeletal specimens of the latter species. CT scans provide
simultaneous study of both articulated and disarticulated elements, allowing us
to describe and document the morphology of the skull with exceptional precision
and detail. The description of the skull of Elgaria panamintina serves as a
generalization for all Elgaria; here we provide the first complete description of
the skull of this genus for future uses in morphological and phylogenetic studies
of both extant species and fossils.
PMID- 29953470
TI - Genetic combining ability of coriander genotypes for agronomic and phytochemical
traits in response to contrasting irrigation regimes.
AB - Knowledge of genetic combining ability and gene action would help breeders to
choose suitable parents and devise an appropriate breeding strategy for
coriander. In the present study, six diverse genotypes of coriander, their 15 F1s
and 15 F2s were evaluated through randomized complete block design with three
replications to study genetic combining ability for agronomic and phytochemical
traits in coriander. Plants were subjected to well-watered (WW), mild water
deficit stress (MWDS) and severe water-deficit stress (SWDS) irrigation regimes.
The results indicate that water-deficit stress decreased all of the measured
traits in both the F1 and F2 generations. General combining ability and specific
combining ability effects were highly significant for all of the traits in both
the F1 and F2 generations. Additive gene action was predominant for phonology and
fruit yield component traits in all irrigation regimes in both the F1 and F2
generations. For fatty acid content and total lipid yield, non-additive gene
action was predominant in the F1 generation while additive gene action was
predominant in the F2 generation under MWDS and SWDS conditions. The P4 parent
had the highest general combining ability for fruit yield components in both the
F1 and F2 generations. The P6 parent had the highest general combining ability
for phenological and phytochemical traits. The P4 and P6 parents are promising
material to develop early flowering and early maturing genotypes coupled with
high total lipids in advanced generations of segregation.
PMID- 29953471
TI - The study design elements employed by researchers in preclinical animal
experiments from two research domains and implications for automation of
systematic reviews.
AB - Systematic reviews are increasingly using data from preclinical animal
experiments in evidence networks. Further, there are ever-increasing efforts to
automate aspects of the systematic review process. When assessing systematic bias
and unit-of-analysis errors in preclinical experiments, it is critical to
understand the study design elements employed by investigators. Such information
can also inform prioritization of automation efforts that allow the
identification of the most common issues. The aim of this study was to identify
the design elements used by investigators in preclinical research in order to
inform unique aspects of assessment of bias and error in preclinical research.
Using 100 preclinical experiments each related to brain trauma and toxicology, we
assessed design elements described by the investigators. We evaluated Methods and
Materials sections of reports for descriptions of the following design elements:
1) use of comparison group, 2) unit of allocation of the interventions to study
units, 3) arrangement of factors, 4) method of factor allocation to study units,
5) concealment of the factors during allocation and outcome assessment, 6)
independence of study units, and 7) nature of factors. Many investigators
reported using design elements that suggested the potential for unit-of-analysis
errors, i.e., descriptions of repeated measurements of the outcome (94/200) and
descriptions of potential for pseudo-replication (99/200). Use of complex factor
arrangements was common, with 112 experiments using some form of factorial design
(complete, incomplete or split-plot-like). In the toxicology dataset, 20 of the
100 experiments appeared to use a split-plot-like design, although no
investigators used this term. The common use of repeated measures and factorial
designs means understanding bias and error in preclinical experimental design
might require greater expertise than simple parallel designs. Similarly, use of
complex factor arrangements creates novel challenges for accurate automation of
data extraction and bias and error assessment in preclinical experiments.
PMID- 29953472
TI - One day you'll wake up and won't have to go to work: The impact of changes in
time use on mental health following retirement.
AB - BACKGROUND: Retirement is a life transition involving an obligatory change in how
people use their time. Because there are strong associations between use of time
and health, different changes in time use following retirement may have different
impacts on mental health. METHODS: 105 participants were followed from 6 months
before retirement to 12 months after retirement. At each time-point, use of time
was quantified using a validated computerised 24-hour recall. Depression, anxiety
and stress were assessed using the Depression, Anxiety and Stress Scales
(DASS21), well-being with the Short Warwick-Edinburgh Mental Well-being Scale
(SWEMWBS), life satisfaction with the Australian Unity Personal Well-being Index
(AUPWI), and self-esteem with the Rosenberg Self-Esteem Scale. Time-use data were
analysed using compositional data analysis, which treats the 24-h day as a
holistic "activity composition" rather than as individual activity domains. Time
flow analytics were used to map patterns of change in time use from pre
retirement to post-retirement. Regression analysis was used to determine whether
changes in the activity composition were significantly associated with changes in
mental health. Compositional isotemporal substitution models were used to
illustrate dose-response relationships between changes in time use and
conditional changes in mental health for individual activity domains, such as
sleep, screen time and physical activity. RESULTS: Following retirement, time no
longer spent in work flowed mainly to household chores, sleep, screen time and
quiet time (e.g. reading). Mental health improved overall. Changes in the
activity composition were significantly related to conditional changes in DASS21
total score, depression, stress, and self-esteem, but not to anxiety, well-being
or life satisfaction. Replacing work time with physical activity or sleep was
associated with positive changes in mental health. Effect sizes for 60-minute
substitutions ranged from -0.15 to +0.31. CONCLUSION: Following retirement,
replacing work with physical activity, and to a lesser extent sleep, is
associated with better mental health.
PMID- 29953473
TI - Prevalence, characteristic features, and complications associated with the
occurrence of unerupted permanent incisors.
AB - This study examined the prevalence, characteristic features, and complications
associated with the occurrence of unerupted permanent incisors among children and
adolescents attending a university dental teaching hospital. A retrospective
review was performed of the clinical records of children and adolescents who
attended the Prince Philip Dental Hospital, Hong Kong between 2005 and 2014. All
patients who had at least one unerupted permanent incisor tooth were included. A
total of 266 subjects with 320 unerupted permanent incisors were identified. The
prevalence of unerupted permanent incisors among children and adolescents was
2.0%. Permanent maxillary central incisors (70.6%) were the most commonly
affected teeth. The most common cause for unerupted incisors were dilacerations
(n = 83, 36.7%) for maxillary central incisors; developmental dental anomalies (n
= 22; 30.6%) together with unfavorable root development (n = 22; 30.6%) for
maxillary laterals incisors; and abnormal tooth/tissue ratio (n = 11, 50.0%) for
mandibular incisors. A majority of unerupted incisors presented with
complications the most common being ectopic/displacement/rotation of the
unerupted incisors (46.6%), loss of space (36.9%) and midline shift (27.5%). In
conclusion, the causes were distinct for different manifestations of unerupted
permanent incisors. As the majority of unerupted incisors presented with
complications, a systematic and organized method of history taking as well as
clinical and radiographic examinations is mandatory in the diagnosis of unerupted
permanent incisors.
PMID- 29953474
TI - Comparison of chikungunya viruses generated using infectious clone or the
Infectious Subgenomic Amplicons (ISA) method in Aedes mosquitoes.
AB - Reverse genetics systems provide the opportunity to manipulate viral genomes and
have been widely used to study RNA viruses and to develop new antiviral compounds
and vaccine strategies. The recently described method called ISA (Infectious
Subgenomic Amplicons) gives the possibility to rescue RNA viruses in days. We
demonstrated in cell culture that the use of the ISA method led to a higher
genetic diversity of viral populations than that observed using infectious clone
technology. However, no replicative fitness difference was observed. In the
present study, we used the chikungunya virus as a model to compare in Aedes
aegypti and Aedes albopictus mosquitoes the genotypic and phenotypic
characteristics of viruses produced either from an infectious clone or using the
ISA method. We confirmed the results found in cellulo corroborating that the use
of the ISA method was associated with higher genetic diversity of viral
populations in mosquitoes but did not affect the vector competence validating its
use for in vivo experiments.
PMID- 29953475
TI - Barriers and facilitators to physical activity among urban residents with
diabetes in Nepal.
AB - INTRODUCTION: Physical activity is an important component of type 2 diabetes
management. Physical activity level among general population in Nepal is reported
to vary considerably. However, knowledge on physical activity in Nepali diabetics
is very limited. Engagement in physical activity could be influenced by
perception of barriers against adopting the behavior and benefits of adopting it.
This study explores the prevalence of physical activity and factors that promote
and hinder the behavior among urban residing diabetic patients from Nepal.
METHODS: A descriptive cross-sectional design was adopted using a simple random
sampling of type 2 diabetic patients from two diabetes clinics at Lalitpur and
Kaski districts of Nepal. Two hundred and seventy participants were surveyed to
obtain information on physical activity using Global Physical Activity
Questionnaire. Metabolic equivalent values were calculated and categorized into
high, moderate and low levels of physical activity. The information on perceived
facilitators and barriers was collected by Exercise Barriers and Benefits Survey
scale. Odds ratios and 95% confidence intervals of the measures were estimated
using multinomial logistic regression. RESULTS: The study showed relatively high
prevalence of physical activity among the urban Nepali diabetic patients; 52%
were moderately active and 28% highly active. Travel and work-related activities
were the major contributors. Male participants, educated and those living in
extended families were more motivated for physical activity than their
counterparts. Physical fitness, strength and flexibility, better sleep at night,
social interaction and longevity, were identified as the major facilitators.
Family responsibilities, busy schedule and family discouragement were identified
as barriers against being physically active. CONCLUSION: The diabetic patients
were mostly moderately physically active. Future research could explore different
context-specific ways of remaining physically active, apart from walking and
doing household chores. More focus should also be placed on leisure time physical
activity as it was found to be low. Interventions could be designed by promoting
the facilitators and addressing the barriers of physical activity, which is
likely to reduce the healthcare costs of management of diabetic complications.
PMID- 29953476
TI - Cost-effectiveness analysis of capecitabine monotherapy versus capecitabine plus
oxaliplatin in elderly patients with advanced gastric cancer.
AB - BACKGROUND: There is no single standard chemotherapy regimen for elderly patients
with advanced gastric cancer (AGC). A phase III trial has confirmed that both
capecitabine monotherapy and capecitabine plus oxaliplatin are well tolerated for
elderly patients with AGC, but their economic influence in China is unknown.
OBJECTIVE: The purpose of this cost-effectiveness analysis was to estimate the
effects of capecitabine monotherapy and capecitabine plus oxaliplatin in elderly
patients with AGC on health and economic outcomes in China. METHODS: We created a
Markov model based on data from a Korean clinical phase III trial to analyze the
cost-effectiveness of the treatment of elderly patients in the capecitabine
monotherapy (X) group and capecitabine plus oxaliplatin (XELOX) group. The costs
were obtained from published reports and the local health system. The utilities
were assumed on the basis of the published literature. Costs, quality-adjusted
life years (QALYs), and incremental cost-effectiveness ratios (ICER) were
estimated. One-way and probabilistic sensitivity analyses (Monte Carlo
simulations) were performed. RESULTS: In the cost-effectiveness analysis, X had a
lower total cost ($45,731.68) and cost-effectiveness ratio ($65,918.93/QALY). The
one-way sensitivity analysis suggested that the most influential parameter was
the risk of requiring second-line chemotherapy in XELOX group. The probabilistic
sensitivity analysis predicted that the X regimen was cost-effective 100% of the
time, given a willingness-to-pay threshold of $26,598. CONCLUSIONS: Our findings
show that the XELOX regimen is less cost-effective compared to the X regimen for
elderly patients with AGC in China from a Chinese healthcare perspective.
PMID- 29953477
TI - Could chronic Vardenafil administration influence the cardiovascular risk in men
with type 2 diabetes mellitus?
AB - INTRODUCTION: Appropriate algorithms for the prediction of cardiovascular risk
are strongly suggested in clinical practice, although still controversial. In
type 2 diabetes mellitus (T2DM), the beneficial effect of phosphodiesterase (PDE)
5 inhibitors is demonstrated on endothelial function but not on the estimation of
cardiovascular risk. AIM: To study whether the chronic Vardenafil administration
to men with T2DM influences variables correlated with the predicted long-term
cardiovascular risk calculated by different validated algorithms. METHODS: Per
protocol analysis of a longitudinal, prospective, randomized, placebo-controlled,
double-blind, investigator-started, clinical trial. 54 male patients affected by
T2DM were assigned to study (26patients) and control-group (28patients),
respectively. The study included a treatment phase (24weeks) (Vardenafil/placebo
10mg twice-daily) and a follow-up phase (24weeks). Three time points were
considered: baseline(V0), end of treatment(V1) and end of the study(V2).
Parameters evaluated: endothelial health-related parameters and cardiovascular
risk, assessed by calculating the Framingham (coronary hart disease [CHD],
myocardial infarction [MI], stroke and cardiovascular disease [CVD]), ASSIGN and
CUORE equations. RESULTS: Predicted cardiovascular risk at ten years resulted
different using the three algorithms chosen, without differences between study
and control groups and among visits. IL-6 was directly related to CHD, CVD and
CUORE scores at V1 and with MI and STROKE at V2. Similarly, hs-CRP was directly
related to CHD, MI, STROKE and CUORE only at V1 in the study group. Testosterone
serum levels were inversely related to CHD and MI at V1 in study group.
DISCUSSION: The predicted cardiovascular risk is different depending on the
algorithm chosen. Despite no predictive risk reduction after six months of
treatment, a possible effect of Vardenafil could be hypothesized through its
action on inflammation markers reduction and through restoration of normal
testosterone levels.
PMID- 29953478
TI - Voxel-based 18F-FET PET segmentation and automatic clustering of tumor voxels: A
significant association with IDH1 mutation status and survival in patients with
gliomas.
AB - INTRODUCTION: Aim was to develop a full automatic clustering approach of the time
activity curves (TAC) from dynamic 18F-FET PET and evaluate its association with
IDH1 mutation status and survival in patients with gliomas. METHODS: Thirty-seven
patients (mean age: 45+/-13 y) with newly diagnosed gliomas and dynamic 18F-FET
PET before any histopathologic investigation or treatment were retrospectively
included. Each dynamic 18F-FET PET was realigned to the first image and spatially
normalized in the Montreal Neurological Institute template. A tumor mask was semi
automatically generated from Z-score maps. Each brain tumor voxel was clustered
in one of the 3 following centroids using dynamic time warping and k-means
clustering (centroid #1: slowly increasing slope; centroid #2: rapidly increasing
followed by slowly decreasing slope; and centroid #3: rapidly increasing followed
by rapidly decreasing slope). The percentage of each dynamic 18F-FET TAC within
tumors and other conventional 18F-FET PET parameters (maximum and mean tumor-to
brain ratios [TBRmax and TBRmean], time-to-peak [TTP] and slope) was compared
between wild-type and IDH1 mutant tumors. Their prognostic value was assessed in
terms of progression free-survival (PFS) and overall survival (OS) by Kaplan
Meier estimates. RESULTS: Twenty patients were IDH1 wild-type and 17 IDH1 mutant.
Higher percentage of centroid #1 and centroid #3 within tumors were positively (P
= 0.016) and negatively (P = 0.01) correlated with IDH1 mutated status. Also,
TBRmax, TBRmean, TTP, and slope discriminated significantly between tumors with
and without IDH1 mutation (P range 0.01 to 0.04). Progression occurred in 22
patients (59%) at a median of 13.1 months (7.6-37.6 months) and 13 patients (35%)
died from tumor progression. Patients with a percentage of centroid #1 > 90% had
a longer survival compared with those with a percentage of centroid #1 < 90% (P =
0.003 for PFS and P = 0.028 for OS). This remained significant after
stratification on IDH1 mutation status (P = 0.029 for PFS and P = 0.034 for OS).
Compared to other conventional 18F-FET PET parameters, TTP and slope were
associated with PFS and OS (P range 0.009 to 0.04). CONCLUSIONS: Based on dynamic
18F-FET PET acquisition, we developed a full automatic clustering approach of TAC
which appears to be a valuable noninvasive diagnostic and prognostic marker in
patients with gliomas.
PMID- 29953479
TI - Experimental estimation of energy absorption during heel strike in human barefoot
walking.
AB - Metabolic energy expenditure during human gait is poorly understood. Mechanical
energy loss during heel strike contributes to this energy expenditure. Previous
work has estimated the energy absorption during heel strike as 0.8 J using an
effective foot mass model. The aim of our study is to investigate the possibility
of determining the energy absorption by more directly estimating the work done by
the ground reaction force, the force-integral method. Concurrently another aim is
to compare this method of direct determination of work to the method of an
effective foot mass model. Participants of our experimental study were asked to
walk barefoot at preferred speed. Ground reaction force and lower leg kinematics
were collected at high sampling frequency (3000 Hz; 1295 Hz), with tight
synchronization. The work done by the ground reaction force is 3.8 J, estimated
by integrating this force over the foot-ankle deformation. The effective mass
model is improved by dropping the assumption that foot-ankle deformation is
maximal at the instant of the impact force peak. On theoretical grounds it is
clear that in the presence of substantial damping that peak force and peak
deformation do not occur simultaneously. The energy absorption results, due the
vertical force only, corresponding to the force-integral method is similar to the
results of the improved application of the effective mass model (2.7 J; 2.5 J).
However the total work done by the ground reaction force calculated by the force
integral method is significantly higher than that of the vertical component
alone. We conclude that direct estimation of the work done by the ground reaction
force is possible and preferable over the use of the effective foot mass model.
Assuming that energy absorbed is lost, the mechanical energy loss of heel strike
is around 3.8 J for preferred walking speeds (~ 1.3 m/s), which contributes to
about 15-20% of the overall metabolic cost of transport.
PMID- 29953480
TI - A study on the use of the Osstell apparatus to evaluate pedicle screw stability:
An in-vitro study using micro-CT.
AB - Pull-out force and insertion torque have not been generally used as
intraoperative measures for the evaluation of pedicle screw stability because of
their invasiveness. On the other hand, resonance frequency analysis is a non
invasive and repeatable technique that has been clinically used in dentistry to
evaluate implant stability e.g. by the Osstell apparatus. In this study, the
characteristics of the implant stability quotient (ISQ) value obtained by the
Osstell apparatus in the field of spinal surgery were investigated. Biomechanical
test materials simulating human bone were used to provide a comparative platform
for evaluating each fixation strength measure, including pull-out force,
insertion torque, and the ISQ value. To perform pull-out force measurement and to
repeat pedicle screw insertion and removal, loosening was artificially created,
and its effect was investigated. The grade of loosening was quantified on a micro
CT image after pedicle screw removal. In the comparison of the 3 fixation
strength measures, the correlations of the ISQ value with the pull-out force (R2
= 0.339 p <0.0001) and the insertion torque (R2 = 0.337 p <0.0001) were lower
than the correlation between pull-out force and insertion torque (R2 = 0.918 p
<0.0001). On a micro-CT study, the material volume of the internal threads
disappeared after destruction of its integrity due to repeated pedicle screw
insertion and removal. Material integrity destruction of the internal threads
decreased only the pull-out force and the insertion torque, but it did not affect
the ISQ value. The ISQ value only decreased when the material volume of the
internal threads disappeared, probably because the ISQ value reflects the
resistance against a force in the perpendicular direction of the screw, unlike
the conventional measures of fixation strength, such as pull-out force and
insertion torque, which reflect axial load.
PMID- 29953481
TI - A two-stage classification method for borehole-wall images with support vector
machine.
AB - Analyzing geological drilling hole images acquired by Axial View Panoramic
Borehole Televiewer (APBT) is a key step to explore the geological structure in a
geological exploration. Conventionally, the borehole images are examined by
technicians, which is inefficient and subjective. In this paper, three dominant
types of borehole-wall images on coal-rock mass structure, namely, border images,
fracture images and intact rock mass images are mainly studied. The traditional
image classification methods based on unified feature extraction algorithm and
single classifier is not effect for the borehole images. Therefore, this paper
proposes a novel two-stage classification approach to improve the classification
performance of borehole images. In the first-stage classification, the border
images are identified from three kinds of images based on texture features and
gray-scale histograms features. For the remaining two types of images, in the
second-stage classification, Gabor filter is first applied to segment the region
of interest (ROI) (such as microfracture, absciss layer and horizontal cracks,
etc.) and the central interference region. Then, using the same feature vector
after eliminating the central interference region, fracture images are separated
from intact rock mass images. We test our two-stage classification system with
real borehole images. The results of experimental show that the two-stage
classification method can effectively classify three major borehole-wall images
with the correction rate of 95.55% in the first stage and 95% in the second
stage.
PMID- 29953482
TI - Resistance exercise-induced muscle fatigue is not accompanied by increased
phosphorylation of ryanodine receptor 1 at serine 2843.
AB - Skeletal muscle fatigue has been shown to be associated with hyperphosphorylation
of the ryanodine receptor 1 at serine 2843 (pRyR1Ser2843), due to chronic
overloading exercise. We investigated whether pRyR1Ser2843, is a mechanism
relevant for muscle fatigue also under acute, in contrast to chronic, muscle
loading. 24 male subjects (age: 24,8+/-3,8; height: 182,8+/-7,2 cm; weight:
82,5+/-9,9 kg) were evenly (n = 6) assigned to the following four different
resistance exercise (RE) groups: hypertrophy- (HYP), strength endurance- (SE),
maximum power- (MAX) at the subjects' 10, 25 and 3 repetition maximum,
respectively, and low intensity (LI) RE with 70% of the 10 repetition maximum.
Each group completed three different RE volumes (1 set, 5, and 10 sets). Muscle
biopsies from the vastus lateralis were taken before and after exercise, analyzed
for pRyR1Ser2843 and examined for association with RE-induced muscle fatigue
which was determined as reduction in maximum isometric force (isoFmax) in the
quadriceps femoris muscle also before and after exercise.The degree of RE-induced
muscle fatigue was specific in terms of set volume as well as of RE mode. isoFmax
was not reduced in any group after one set of RE. Five sets led to a significant
reduction of isoFmax in HYP and SE but not in LI and MAX (p<0,05). Ten sets of
RE, as compared to five sets, exclusively induced further muscle fatigue in LI.
In terms of RE mode differences, isoFmax reduction was generally higher in HYP
and SE than in MAX and Li after five and ten sets of RE (p<0,05). However,
pRyR1Ser2843 did not show any significant regulation, regardless of exercise
condition. We conclude that despite its relevance in reducing muscle
contractility in chronic overloading, pRyR1Ser2843 does not reflect the degree of
muscle fatigue exerted by acute hypertrophy-, strength endurance-, maximum power
and low intensity-oriented exercise.
PMID- 29953483
TI - Does prenatal alcohol exposure cause a metabolic syndrome? (Non-)evidence from a
mouse model of fetal alcohol spectrum disorder.
AB - Although prenatal alcohol exposure (PAE) reduces offspring growth, it may
increase obesity risk at adolescence. Animal models of PAE display glucose
intolerance and increased adiposity, suggesting that PAE causes metabolic
reprogramming. We tested this hypothesis in a mouse model of binge PAE, wherein
pregnant C57Bl/6J females received 3 g/kg alcohol (ETOH) daily from gestational
day 12.5 to 17.5; maltodextrin (MD) and medium chain triglycerides (MCT) served
as isocaloric nutritional controls, and sham (H2O) treatment controlled for
gavage stress. Our comprehensive assessment quantified body composition, energy
expenditure, glucose tolerance, and cardiovascular function in offspring at age
17 weeks. Although ETOH pups were initially lighter than all other groups, they
did not have a unique obesogenic phenotype. Instead, a similar obesogenic
phenotype emerged in all three caloric groups (MCT, MD, ETOH), such that caloric
groups had greater post-weaning weight gain (both sexes), reduced gonadal fat
weight (males), and reduced glucose clearance (males) compared against H2O
offspring. PAE did not affect body composition, respiratory exchange ratio,
metabolic adaption to high-fat or low-fat diet, eating behavior, and blood
pressure, and ETOH values did not differ from those obtained from isocaloric
controls. Exposure to a higher alcohol dose (4.5 g/kg) or a high-fat (60%) diet
did not exacerbate differences in body composition or glucose tolerance. "PAE
specific" effects on postnatal growth, glucose tolerance, adiposity, or
hypertension only emerged when PAE offspring were compared just against H2O
controls, or against MD controls. We conclude that prior reports of obesity and
glucose intolerance in adult PAE offspring reflect the contribution of added
gestational calories, and not alcohol's pharmacologic action. Results suggest
that the increased adiposity risk in FASD is not caused by metabolic
reprogramming, and instead originates from behavioral, medication, and/or dietary
practices. This study highlights the importance of appropriate dietary controls
in nutritional studies of PAE.
PMID- 29953484
TI - Air pollution influences the incidence of otitis media in children: A national
population-based study.
AB - BACKGROUND: Otitis media (OM) is a major reason for children's visits to
physicians and a major cause of their being treated with antibiotics. It not only
causes economic burdens but also influences hearing, speech, and education. To
our knowledge, no nationwide population-based study has assessed the association
between air pollution and OM. Therefore, this study evaluated the association
between air pollution levels and the incidence of OM. METHODS: We identified
cases of OM that occurred in South Korea between January 2011 and December 2012
from the Korea National Health Insurance Service-National Sample Cohort database,
and evaluated its relationship with five air pollutants: particulate matter
(PM10, particulates <=10 MUm in diameter), nitrogen dioxide (NO2), ozone (O3),
sulfur dioxide, and carbon monoxide. Associations between the weekly incidence of
OM and the five air pollutants were analyzed using generalized estimating
equations. Conditional logistic regression analysis was used to obtain odds
ratios (ORs) and their 99.9% Bonferroni-corrected confidence intervals after
adjusting for gender, age, season, and region. RESULTS: We based our analysis on
160,875 hospital visits for OM by children aged <15 years. Correlations with
higher concentrations of the five pollutants showed higher ORs than did the
reference values at most time lags. PM10 had the largest influence on the OM
incidence at a time lag of 0 weeks, whereas NO2 and O3 had the largest impacts on
OM incidence at time lags of 1 and 4 weeks, respectively. CONCLUSION: These
findings support the notion that the incidence of OM is associated with ambient
air pollution.
PMID- 29953485
TI - Effect of pannus formation on the prosthetic heart valve: In vitro demonstration
using particle image velocimetry.
AB - Although hemodynamic influence of the subprosthetic tissue, termed as pannus, may
contribute to prosthetic aortic valve dysfunction, the relationship between
pannus extent and hemodynamics in the prosthetic valve has rarely been reported.
We investigated the fluid dynamics of pannus formation using in vitro experiments
with particle image velocimetry. Subvalvular pannus formation caused substantial
changes in prosthetic valve transvalvular peak velocity, transvalvular pressure
gradient (TPG) and opening angle. Maximum flow velocity and corresponding TPG
were mostly affected by pannus width. When the pannus width was 25% of the valve
diameter, pannus formation elevated TPG to >2.5 times higher than that without
pannus formation. Opening dysfunction was observed only for a pannus involvement
angle of 360 degrees . Although circumferential pannus with an involvement angle
of 360 degrees decreased the opening angle of the valve from approximately 82
degrees to 58 degrees , eccentric pannus with an involvement angle of 180
degrees did not induce valve opening dysfunction. The pannus involvement angle
largely influenced the velocity flow field at the aortic sinus and corresponding
hemodynamic indices, including wall shear stress, principal shear stress and
viscous energy loss distributions. Substantial discrepancy between the velocity
based TPG estimation and direct pressure measurements was observed for prosthetic
valve flow with pannus formation.
PMID- 29953486
TI - Repurposing ebselen for decolonization of vancomycin-resistant enterococci (VRE).
AB - Enterococci represent one of the microbial world's most challenging enigmas.
Colonization of the gastrointestinal tract (GIT) of high-risk/immunocompromised
patients by enterococci exhibiting resistance to vancomycin (VRE) can lead to
life-threating infections, including bloodstream infections and endocarditis.
Decolonization of VRE from the GIT of high-risk patients represents an
alternative method to suppress the risk of the infection. It could be considered
as a preventative measure to protect against VRE infections in high-risk
individuals. Though multiple agents (ramoplanin and bacitracin) have been
evaluated clinically, no drugs are currently approved for use in VRE
decolonization of the GIT. The present study evaluates ebselen, a clinical
molecule, for use as a decolonizing agent against VRE. When evaluated against a
broad array of enterococcal isolates in vitro, ebselen was found to be as potent
as linezolid (minimum inhibitory concentration against 90% of clinical isolates
tested was 2 MUg/ml). Though VRE has a remarkable ability to develop resistance
to antibacterial agents, no resistance to ebselen emerged after a clinical
isolate of vancomycin-resistant E. faecium was serially-passaged with ebselen for
14 days. Against VRE biofilm, a virulence factor that enables the bacteria to
colonize the gut, ebselen demonstrated the ability to both inhibit biofilm
formation and disrupt mature biofilm. Furthermore, in a murine VRE colonization
reduction model, ebselen proved as effective as ramoplanin in reducing the
bacterial shedding and burden of VRE present in the fecal content (by > 99.99%),
cecum, and ileum of mice. Based on the promising results obtained, ebselen
warrants further investigation as a novel decolonizing agent to quell VRE
infection.
PMID- 29953487
TI - Uncovering the fine print of the CreERT2-LoxP system while generating a
conditional knockout mouse model of Ssrp1 gene.
AB - FAcilitates Chromatin Transcription (FACT) is a complex of SSRP1 and SPT16 that
is involved in chromatin remodeling during transcription, replication, and DNA
repair. FACT has been mostly studied in cell-free or single cell model systems
because general FACT knockout (KO) is embryonically lethal (E3.5). FACT levels
are limited to the early stages of development and stem cell niches of adult
tissues. FACT is upregulated in poorly differentiated aggressive tumors.
Importantly, FACT inhibition (RNAi) is lethal for tumors but not normal cells,
making FACT a lucrative target for anticancer therapy. To develop a better
understanding of FACT function in the context of the mammalian organism under
normal physiological conditions and in disease, we aimed to generate a
conditional FACT KO mouse model. Because SPT16 stability is dependent on the
SSRP1-SPT16 association and the presence of SSRP1 mRNA, we targeted the Ssrp1
gene using a CreERT2- LoxP approach to generate the FACT KO model. Here, we
highlight the limitations of the CreERT2-LoxP (Rosa26) system that we encountered
during the generation of this model. In vitro studies showed an inefficient
excision rate of ectopically expressed CreERT2 (retroviral CreERT2) in
fibroblasts with homozygous floxed Ssrp1. In vitro and in vivo studies showed
that the excision efficiency could only be increased with germline expression of
two alleles of Rosa26CreERT2. The expression of one germline Rosa26CreERT2 allele
led to the incomplete excision of Ssrp1. The limited efficiency of the CreERT2
LoxP system may be sufficient for studies involving the deletion of genes that
interfere with cell growth or viability due to the positive selection of the
phenotype. However, it may not be sufficient for studies that involve the
deletion of genes supporting growth, or those crucial for development. Although
CreERT2-LoxP is broadly used, it has limitations that have not been widely
discussed. This paper aims to encourage such discussions.
PMID- 29953489
TI - Correction: Test-retest reliability of myelin imaging in the human spinal cord:
Measurement errors versus region- and aging-induced variations.
AB - [This corrects the article DOI: 10.1371/journal.pone.0189944.].
PMID- 29953488
TI - Loxl2 is dispensable for dermal development, homeostasis and tumour stroma
formation.
AB - Lysyl oxidase-like 2 (LOXL2) is a copper-dependent monoamine oxidase that
contributes to the remodelling of the extracellular matrix (ECM) by cross linkage
of collagen and elastin fibres and has emerged as a potential therapeutic target
in cancer and fibrosis. In the skin, LOXL2 is essential for epidermal cell
polarity and differentiation. However, its role in the dermis has not been
evaluated. We found that Loxl2 is dispensable for mouse dermal development,
maturation and homeostasis, yet affects dermal stiffness. Neither loss of Loxl2
nor increased Loxl2 expression affected dermal architecture following treatment
with the phorbol ester TPA. Furthermore, Loxl2 expression did not alter the
stroma of DMBA-TPA-induced tumours. We conclude that, although Loxl2 is expressed
in both dermis and epidermis, its function appears largely confined to the
epidermis.
PMID- 29953490
TI - Quantitative analysis of optical coherence tomographic angiography (OCT-A) in
patients with non-arteritic anterior ischemic optic neuropathy (NAION)
corresponds to visual function.
AB - PURPOSE: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most
common cause of non-glaucomatous optic neuropathy in older adults. Optical
coherence tomographic angiography (OCT-A) is an emerging, non-invasive method to
study the microvasculature of the posterior pole, including the optic nerve head.
The goal of this study was to assess the vascular changes in the optic nerve head
and peripapillary area associated with NAION using OCT-A. DESIGN: Retrospective
comparative case series. METHODS: We performed OCT-A in 25 eyes (7 acute and 18
non-acute) in 19 patients with NAION. Fellow, unaffected eyes were analyzed for
comparison. Patent macro- and microvascular densities were quantified in the
papillary and peripapillary regions of unaffected, acutely affected, and non
acutely affected eyes and compared across these groups according to laminar
segment and capillary sampling region, and with respect to performance on
automated visual field testing. RESULTS: In acutely affected eyes, OCT-A revealed
a reduction in the signal from the major retinal vessels and dilation of patent
superficial capillaries in the peripapillary area. By contrast, non-acutely
affected eyes showed attenuation of patent capillaries. The peripapillary
choriocapillaris was obscured by edema in acute cases, but was similar between
non-acute and unaffected eyes. The degree of dilation of the superficial
microvasculature in the acute phase and attenuation in the non-acute phase each
correlated inversely with visual field performance. The region of reduced patent
capillary density correlated with the location of visual field defects in 80% of
acute cases and 80% of non-acute cases. CONCLUSIONS: OCT-A reveals a dynamic
shift in the superficial capillary network of the optic nerve head with strong
functional correlates in both the acute and non-acute phases of NAION. Further
study may validate OCT-A as a useful adjunctive diagnostic tool in the evaluation
of ischemic optic neuropathy.
PMID- 29953491
TI - Agreement of Middle brook 7H10 with Lowenstein Jensen and accuracy of the
Sensititre MYCOTB plate using either method as a reference standard for
Mycobacterium tuberculosis first line drug susceptibility testing.
AB - INTRODUCTION: Although Sensititre Mycobacterium tuberculosis (MYCOTB) plate
offers both drug susceptibility testing (DST) and minimum inhibitory
concentration (MIC) results, it has not been evaluated against both Lowenstein
Jensen (LJ) and Middlebrook 7H10 (MB7H10) DST methods at standard critical
concentrations. MATERIALS AND METHODS: We analyzed 76 M. tuberculosis isolates
consisting of 54 isolates from the Uganda National TB drug resistance survey done
December 2009-February 2011 and 22 isolates from the World Health Organization
External Quality Assessment panel for the year 2011. All isolates were tested for
LJ, MB7H10 and MYCOTB plate based DSTs for streptomycin, isoniazid, rifampicin
and ethambutol anti-tuberculosis drugs. The agreement of MB7H10 with LJ and
accuracy of MYCOTB plate using either LJ-DST or MB7H10 as a reference standard
were determined. RESULTS: The agreement (kappa) of MB7H10 with LJ was; 0.687 for
rifampicin, 0.498 for isoniazid, 0.275 for streptomycin and 0.082 for ethambutol
which as almost similar when compared with MYCOTB plate. The sensitivity (95%
confidence interval; CI) of MYCOTB plate when LJ was used as a reference standard
was higher for streptomycin 87.5% (81.6-98.4) followed by isoniazid 75.9% (65.1
95.6) and rifampicin 73.1% (52.2-88.4). When MB7H10 was used as reference
standard, the sensitivity of MYCOTB plate improved significantly; isoniazid 96.2%
(80.3-99.9), rifampicin 94.0 (83.4-98.7) and 93.8% (69.7-99.8). There was good
agreement between MYCOTB plate and MB7H10; 1.00 for ethambutol, 0.959 for
streptomycin, 0.915 for rifampicin and 0.778 for isoniazid. CONCLUSIONS: The
performance of the two culture-based reference standards for phenotypic first
line drug susceptibility testing methods, LJ and MB7H10, varied much even with
acceptable MYCOTB plate MICs. There was acceptable agreement and accuracy of
MYCOTB plate for drug susceptibility testing when MB7H10 was used as reference
standard than with LJ-DST. Results from MIC information makes the MYCOTB plate
more suitable for guiding clinicians on the choice of the most appropriate TB
treatment regimen as well as limits of detection for TB drug resistance.
PMID- 29953492
TI - SIMPLE binds specifically to PI4P through SIMPLE-like domain and participates in
protein trafficking in the trans-Golgi network and/or recycling endosomes.
AB - Small integral membrane protein of the lysosome/late endosome (SIMPLE) is a 161
amino acid cellular protein that contains a characteristic C-terminal domain
known as the SIMPLE-like domain (SLD), which is well conserved among species.
Several studies have demonstrated that SIMPLE localizes to the trans-Golgi
network (TGN), early endosomes, lysosomes, multivesicular bodies, aggresomes and
the plasma membrane. However, the amino acid regions responsible for its
subcellular localization have not yet been identified. The SLD resembles the FYVE
domain, which binds phosphatidylinositol (3)-phosphate (PI3P) and determines the
subcellular localization of FYVE domain-containing proteins. In the present
study, we have found that SIMPLE binds specifically to PI4P through its SLD.
SIMPLE co-localized with PI4P and Rab11, a marker for recycling endosomes (REs,
organelles enriched in PI4P) in both the IMS32 mouse Schwann cell line and Hela
cells. Sucrose density-gradient centrifugation revealed that SIMPLE co
fractionated with syntaxin-6 (a TGN marker) and Rab11. We have also found that
SIMPLE knockdown impeded recycling of transferrin and of transferrin receptor.
Our overall results indicate that SIMPLE may regulate protein trafficking
physiologically by localizing to the TGN and/or REs by binding PI4P.
PMID- 29953493
TI - Potential effects of climate change on dengue transmission dynamics in Korea.
AB - Dengue fever is a major international public health concern, with more than 55%
of the world population at risk of infection. Recent climate changes related to
global warming have increased the potential risk of domestic outbreaks of dengue
in Korea. In this study, we develop a two-strain dengue model associated with
climate-dependent parameters based on Representative Concentration Pathway (RCP)
scenarios provided by the Korea Meteorological Administration. We assess the
potential risks of dengue outbreaks by means of the vector capacity and intensity
under various RCP scenarios. A sensitivity analysis of the temperature-dependent
parameters is performed to explore the effects of climate change on dengue
transmission dynamics. Our results demonstrate that a higher temperature
significantly enhances the potential threat of domestic dengue outbreaks in
Korea. Furthermore, we investigate the effects of countermeasures on the
cumulative incidence of humans and vectors. The current main control measures
(comprising only travel restrictions) for infected humans in Korea are not as
effective as combined control measures (travel restrictions and vector control),
dramatically reducing the possibilities of dengue outbreaks.
PMID- 29953494
TI - Combined neutralization of interferon gamma and tumor necrosis factor alpha
induces IL-4 production but has no direct additive impact on parasite burden in
splenic cultures of human visceral leishmaniasis.
AB - Immune activating cytokines Interferon (IFN)-gamma and Tumor necrosis factor
(TNF)-alpha are known to activate macrophages for killing of Leishmania parasite.
IFN-gamma provides therapeutic potential while TNF-alpha has been recognized to
mediate protection in visceral model of infection. In the present study we
investigated whether combination of IFN-gamma and TNF-alpha has better
therapeutic strength than individually using one of these cytokines in Visceral
Leishmaniasis (VL) patients. We performed combined blockade of IFN-gamma and TNF
alpha in VL splenic biopsies and demonstrated it's impact on number of viable
amastigotes and cytokine production. Additionally, selective depletion of splenic
cell subsets was performed to establish the cellular sources of IFN-gamma and TNF
alpha. Treatment of splenic aspirate cells with combination of anti-IFN-gamma and
anti-TNF-alpha monoclonal antibodies for 72 hours enabled no direct additive
impact of these cytokines on parasite replication and IL-10 secretion, but IL-4
production was induced. Further assessment of splenic biopsies put forward CD4+ T
cells as a source of IFN-gamma whereas CD14+ cells contribute towards TNF-alpha
production. Overall our results suggest, the interplay of pro-inflammatory
cytokines IFN-gamma derived from CD4+T lymphocytes and TNF-alpha from CD14+ cells
has no direct additive impact on parasite replication but induces IL-4
production. Our data does not support direct targeting of IFN-gamma and TNF-alpha
for combination therapy but targeting these cytokines as an adjuvant in patients
with exaggerated tissue inflammatory responses can have favourable patient
outcome.
PMID- 29953496
TI - Screen-based sedentary behaviour and adiposity among school children: Results
from International Study of Childhood Obesity, Lifestyle and the Environment
(ISCOLE) - Kenya.
AB - BACKGROUND: High levels of sedentary behaviours have been independently
associated with several negative health indicators, including obesity. Screen
time (ST) is often used as a contributing measure of sedentary time. It is
recommended that children spend no more than 2 hours on recreational sedentary
screen-based activities daily. We describe screen-based sedentary time of urban
school children and examine the associations between body mass index (BMI) and
percent Body Fat (%BF) with ST levels. METHODS: Data were collected from 563
children aged 9 to 11 years attending 29 non-boarding primary schools in Nairobi,
Kenya, as part of the International Study of Childhood Obesity, Lifestyle and the
Environment (ISCOLE). Data were analysed to test for associations between ST and
sex, type of school attended (public verses private), Socioeconomic status,
adiposity, and access to electronic devices. We also assessed participants' ST on
school and weekend days. RESULTS: Of the participants recruited, 15.5% had high
ST levels, 67.9% spent no more than 2 hours in recreational screen activities on
school days while 74.2% did not meet the guidelines on weekend days. Participants
sex was associated with daily ST (t = 3.5, p<0.001), ST on the weekend (t = 3.9,
p <0.001) and total ST per week (t = 3.5, p<0.001) with males having higher ST
than females. ST was associated with type of school for daily ST (t = 3.6, p
<0.001), ST on the weekend (t = 4.5, p<0.001) and total ST per week (t = 3.6,
p<0.001) where private schools pupils had higher ST. ST was not associated with
BMI. ST was not associated with %BF except on weekend days (p = 0.038) where
those classified as overfat/obese (fat) had higher ST. CONCLUSIONS: A large
proportion of children spend more time than recommended on screen activities
particularly on weekend days. Strategies to improve healthy living should focus
on the reduction of sedentary ST for school-aged children.
PMID- 29953495
TI - Measuring wealth in rural communities: Lessons from the Sanitation, Hygiene,
Infant Nutrition Efficacy (SHINE) trial.
AB - BACKGROUND: Poverty and human capital development are inextricably linked and
therefore research on human capital typically incorporates measures of economic
well-being. In the context of randomized trials of health interventions, for
example, such measures are used to: 1) assess baseline balance; 2) estimate
covariate-adjusted analyses; and 3) conduct subgroup analyses. Many factors
characterize economic well-being, however, and analysts often generate summary
measures such as indices of household socio-economic status or wealth. In this
paper, a household wealth index is developed and tested for participants in the
cluster-randomized Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) trial
in rural Zimbabwe. METHODS: Building on the approach used in the Zimbabwe
Demographic and Health Survey (ZDHS), we combined a set of housing
characteristics, ownership of assets and agricultural resources into a wealth
index using principal component analysis (PCA) on binary variables. The index was
assessed for internal and external validity. Its sensitivity was examined
considering an expanded set of variables and an alternative statistical approach
of polychoric PCA. Correlation between indices was determined using the
Spearman's rank correlation coefficient and agreement between quintiles using a
linear weighted Kappa statistic. Using the 2015 ZDHS data, we constructed a
separate index and applied the loadings resulting from that analysis to the SHINE
study population, to compare the wealth distribution in the SHINE study with
rural Zimbabwe. RESULTS: The derived indices using the different methods were
highly correlated (r>0.9), and the wealth quintiles derived from the different
indices had substantial to near perfect agreement (linear weighted Kappa>0.7).
The indices were strongly associated with a range of assets and other wealth
measures, indicating both internal and external validity. Households in SHINE
were modestly wealthier than the overall population of households in rural
Zimbabwe. CONCLUSION: The SHINE wealth index developed here is a valid and robust
measure of wealth in the sample.
PMID- 29953497
TI - Role of forensic odontology in the identification of victims of major mass
disasters across the world: A systematic review.
AB - BACKGROUND: Forensic odontology (FO) is regarded in the literature as one of the
most reliable and economical scientific methods for victim identification in mass
disasters (MDs). The present paper systematically reviews the role of forensic
odontologists in various global MDs. METHOD: A comprehensive search of the
literature databases (PubMed, Medline, SCOPUS, Web of Science and Google
Scholar), along with cross-referencing published peer-reviewed articles, was
conducted. The search included full texts, abstracts or titles, had no inclusion
year limit (searched until September 2017) and was limited to the English
language. Keywords included a combination of 'Forensic odontology', 'Dental
records', 'Victim identification', 'Natural mass disaster', 'Criminal mass
disaster', 'Accidental mass disaster' and 'Victim disaster'. RESULTS: Of the
included disasters (20), 12 (57.14%) were accidental, 5 (23.80%) natural and 3
(19.04%) were criminal. The maximum number of victims was associated with the
Japan tsunami (15892), followed by the Thailand tsunami (4280) and the Estonia
ferry disaster (852). A total of 23654 victims were reported, of which 20569
(86.96%) were positively identified. Reports from 17 MDs included the use of FO
in victim identification [3025 (14.70%) cases]. In addition, 1094 victims (5.31%;
from 7 papers) were identified using FO in combination with other methodologies.
The highest percentage of victims was identified using FO following the Kentucky
air crash (47; 100%), followed by the Newark air crash (38; 76%), the Nepal air
crash (10; 71.42%), the France air crash (56; 65.88%), the Australian bushfire
(14; 63.63%), and the Estonia ferry disaster (57; 60.63%). CONCLUSION: FO has
played a significant role in victim identification in several MDs around the
world. The success of FO-based identification is heavily dependent on the
availability of ante-mortem records from general dental practitioners. Hence,
adequate knowledge about FO and appropriate dental record keeping among general
dental practitioners are critical.
PMID- 29953498
TI - RNA-Seq analysis revealed genes associated with drought stress response in kabuli
chickpea (Cicer arietinum L.).
AB - Drought is the most important constraint that effects chickpea production
globally. RNA-Seq has great potential to dissect the molecular mechanisms of
tolerance to environmental stresses. Transcriptome profiles in roots and shoots
of two contrasting Iranian kabuli chickpea genotypes (Bivanij and Hashem) were
investigated under water-limited conditions at early flowering stage using RNA
Seq approach. A total of 4,572 differentially expressed genes (DEGs) were
identified. Of these, 261 and 169 drought stress responsive genes were identified
in the shoots and the roots, respectively, and 17 genes were common in the shoots
and the roots. Gene Ontology (GO) analysis revealed several sub-categories
related to the stress, including response to stress, defense response and
response to stimulus in the tolerant genotype Bivanij as compared to the
sensitive genotype Hashem under drought stress. In addition, several
Transcription factors (TFs) were identified in major metabolic pathways such as,
ABA, proline and flavonoid biosynthesis. Furthermore, a number of the DEGs were
observed in "QTL-hotspot" regions which were reported earlier in chickpea.
Drought tolerance dissection in the genotypes revealed that the genes and the
pathways involved in shoots of Bivanij were the most important factor to make a
difference between the genotypes for drought tolerance. The identified TFs in the
experiment, particularly those which were up-regulated in shoots of Bivanij
during drought stress, were potential candidates for enhancing tolerance to
drought.
PMID- 29953499
TI - Autocleavage of the paracaspase MALT1 at Arg-781 attenuates NF-kappaB signaling
and regulates the growth of activated B-cell like diffuse large B-cell lymphoma
cells.
AB - MALT1 controls several receptors-mediated signaling to nuclear factor kappaB (NF
kappaB) through both its scaffold and protease function. MALT1 protease activity
is shown to inactivate several negative regulators of NF-kappaB signaling and
augment NF-kappaB activation ability. In this study, MALT1 was demonstrated to
autoprocess itself in the presence of oligomerization-competent BCL10. Cleavage
occurred after Arginine 781 located in the C-terminus of MALT1. Shortened MALT1
cleavage products showed attenuated binding ability with TRAF6. Its NF-kappaB
activation ability was also weakened. Various MALT1 constructs including wild
type, catalytically-inactive (MALT1_C464A), cleavage-defective (MALT1_R781L), or
truncated (MALT1_1-781) form of MALT1 was introduced into MALT1-knocked-down
Jurkat T cells. Cleavage-defective MALT1_R781L retained its proteolytic and
initial IkappaBalpha phosphorylation activity as MALT1. Truncated MALT1_1-781
mutant showed weakness in IkappaBalpha phosphorylation and the expression of NF
kappaB targets IL-2 and IFN-gamma. Cleavage at R781 was detectable but marginal
after activation with TPA/ionomycin or anti-CD3 antibody in lymphocytes. However,
cleavage at R781 was evident in ABC-DLBCL cells such as OCI-Ly3, HBL-1. HBL-1
cells with induced expression of catalytically-inactive MALT1_C464A or cleavage
defective MALT1_R781L exhibited characteristic of retarded-growth. These findings
suggested that cleavage at R781 of MALT1 played a role in the survival of ABC
DLBCL cells.
PMID- 29953500
TI - Potential role of HIF-1-responsive microRNA210/HIF3 axis on gemcitabine
resistance in cholangiocarcinoma cells.
AB - MicroRNA-210 (miR-210) is a robust target for hypoxia-inducible factor, and its
overexpression has been detected in a variety of solid tumors. However, the role
of miR-210 in the development, progression and response to therapy in
cholangiocarcinoma (CCA) remains undefined. We report here that high miR-210
expression was significantly correlated with the shorter survival of CCA
patients. Overexpression of miR-210 inhibited CCA cell proliferation at the G2/M
phase and reduced the gemcitabine sensitivity in CCA cells under CoCl2-induced
pseudohypoxia. Concomitantly, inhibition of endogenous miR-210 activity using
miRNA sponges increased cell proliferation under CoCl2-induced pseudohypoxia,
resulting in an increase in gemcitabine sensitivity in CCA cells. We showed that
HIF-3alpha, a negative controller of HIF-1alpha, was a target of miR-210
constituting a feed-forward hypoxic regulatory loop. Our data suggest an
important role of miR-210 in sustaining HIF-1alpha activity via the suppression
of HIF-3alpha, regulating cell growth and chemotherapeutic drug resistance in
CCA.
PMID- 29953501
TI - Cross-cultural adaptation and psychometric evaluation of the Sinhala version of
Lawton Instrumental Activities of Daily Living Scale.
AB - INTRODUCTION: Instrumental activities of daily living (IADL) are cognitively
complex activities related to independent living in the community. Robust IADL
scales are needed, however the psychometric properties of instruments have been
little evaluated. There is no validated instrument for Sri Lankan older
populations. Sri Lanka has the highest proportion of older people in South Asia
with rapid population ageing. Therefore, it is essential to have standard
instruments to assess activity limitations. We aimed to cross-culturally adapt
the original Lawton Instrumental Activities of Daily Living Scale from English to
Sinhala and evaluate the psychometric properties of the Sinhala version. METHODS:
Cross-cultural adaptation of the instrument was performed. The instrument was
validated in a sample of 702 community-dwelling older adults aged 60 years and
above in Sri Lanka. Reliability (internal consistency and inter-rater
reliability) was assessed. Construct validity of the scale was evaluated by
performing exploratory and confirmatory factor analysis and testing convergent
and divergent validity. RESULTS: The Lawton IADL scale was successfully adapted
to Sri Lankan context. Internal consistency of the scale was very high
(Cronbach's alpha = 0.91). Very good inter-rater reliability was observed with
very good agreement for all items. Inter-class correlations for overall IADL
score ranged from 0.57 to 0.91. Results of the exploratory and confirmatory
factor analyses supported the unidimensionality of the scale. Goodness of fit
indices in confirmatory factor analysis were in acceptable range (CFI = 0.98,
SRMR = 0.06, NNFI = 0.97). Strength of associations were significant and in the
expected direction. Results of the known group validity were also significant,
confirming the convergent and divergent validity. CONCLUSION: The Lawton IADL
scale was successfully translated and culturally adapted to Sinhala language. The
Sinhala version demonstrated excellent reliability and construct validity. Given
good psychometric properties, this scale would be recommended for use in future
research.
PMID- 29953502
TI - Pilot study assessing the structural changes in posttrabecular aqueous humor
outflow pathway after trabecular meshwork surgery using swept-source optical
coherence tomography.
AB - This study evaluated the morphological change in aqueous humor outflow (AHO)
pathways using swept-source optical coherence tomography (SS-OCT) volumetric
scans in glaucoma patients before and after glaucoma surgery. In this prospective
observational case series, 15 eyes (13 patients) with glaucoma were treated with
120-degree Trabectome or 360-degree suture trabeculotomy and followed up for 3
months. B-scan images of the posttrabecular AHO pathway were reconstructed and
the pathway areas were evaluated, before and after surgery. Changes in
posttrabecular AHO pathway were qualitatively classified as "increased", "non
significant change", and "decreased" on reconstructed B-scan images. Quantitative
measurements of the posttrabecular AHO pathway areas were performed pre- and
postoperatively. Factors associated with both qualitative and quantitative
changes in AHO pathway were investigated. From 30 regions (15 nasal and 15
temporal regions) in the 15 eyes, AHO pathways were analyzable in 20 regions pre-
and postoperatively. Qualitative assessments of the pathway changes were
"increased" in 8 regions, "non-significant change" in 9 regions, and "decreased"
in 3 regions. Quantitative assessments of the average pathway area did not change
significantly (from 3155+/-1633 pixels preoperatively to 3212+/-1684 pixels
postoperatively, P = 0.50). All parameters relating to intraocular pressure
changes or the surgical location were not associated with postoperative AHO
pathway change. The intrascleral AHO pathway could be well visualized in glaucoma
patients pre- and postoperatively using swept-source optical coherence
tomography. However, structural changes in the AHO pathway assessed by SS-OCT
were not significant after trabecular-targeted glaucoma surgery. Functional
assessments of AHO are needed in future studies.
PMID- 29953503
TI - The role of polyproline motifs in the histidine kinase EnvZ.
AB - Although distinct amino acid motifs containing consecutive prolines (polyP) cause
ribosome stalling, which necessitates recruitment of the translation elongation
factor P (EF-P), they occur strikingly often in bacterial proteomes. For example,
polyP motifs are found in more than half of all histidine kinases in Escherichia
coli K-12, which raises the question of their role(s) in receptor function. Here
we have investigated the roles of two polyP motifs in the osmosensor and
histidine kinase EnvZ. We show that the IPPPL motif in the HAMP domain is
required for dimerization of EnvZ. Moreover, replacement of the prolines in this
motif by alanines disables the receptor's sensor function. The second motif,
VVPPA, which is located in the periplasmic domain, was found to be required for
interaction with the modulator protein MzrA. Our study also reveals that polyP
dependent stalling has little effect on EnvZ levels. Hence, both polyP motifs in
EnvZ are primarily involved in protein-protein interaction. Furthermore, while
the first motif occurs in almost all EnvZ homologues, the second motif is only
found in species that have MzrA, indicating co-evolution of the two proteins.
PMID- 29953505
TI - Structural modification of the tripeptide KPV by reductive "glycoalkylation" of
the lysine residue.
AB - Peptides that exhibit enzymatic or hormonal activities are regulatory factors and
desirable therapeutic drugs because of their high target specificity and minimal
side effects. Unfortunately, these drugs are susceptible to enzymatic
degradation, leading to their rapid elimination and thereby demanding frequent
dosage. Structurally modified forms of some peptide drugs have shown enhanced
pharmacokinetics, improving their oral bioavailability. Here, we discuss a novel
glycomimetic approach to modify lysine residues in peptides. In a model system,
the epsilon-amine of Ts-Lys-OMe was reductively alkylated with a glucose
derivative to afford a dihydroxylated piperidine in place of the amine. A similar
modification was applied to H-KPV-NH2, a tripeptide derived from the alpha
melanocyte stimulating hormone (alpha-MSH) reported to have antimicrobial and
anti-inflammatory properties. Antimicrobial assays, under a variety of
conditions, showed no activity for Ac-KPV-NH2 or the alpha- or epsilon
glycoalkylated analogs. Glycoalkylated peptides did, however, show stability
toward proteolytic enzymes.
PMID- 29953504
TI - Potential involvement of neutrophils in human thyroid cancer.
AB - BACKGROUND: Neutrophil functions have long been regarded as limited to acute
inflammation and the defense against microbes. The role(s) of neutrophils in
cancer remain poorly understood. Neutrophils infiltrate tumors and are key
effector cells in the orchestration of inflammatory responses. Thyroid cancer
(TC) is the most recurrent endocrine malignant tumor and is responsible for 70%
of deaths due to endocrine cancers. No studies are so far available on the role
of neutrophils in TC. OBJECTIVE: Our purpose was to study the involvement of
tumor-associated neutrophils in TC. METHODS: Highly purified human neutrophils
(>99%) from healthy donors were stimulated in vitro with conditioned media
derived from TC cell lines TPC1 and 8505c (TC-CMs). Neutrophil functions (e.g.,
chemotaxis, activation, plasticity, survival, gene expression, and protein
release) were evaluated. RESULTS: TC-derived soluble factors promoted neutrophil
chemotaxis and survival. Neutrophil chemotaxis toward a TC-CM was mediated, at
least in part, by CXCL8/IL-8, and survival was mediated by granulocyte-macrophage
colony-stimulating factor (GM-CSF). In addition, each TC-CM induced morphological
changes and activation of neutrophils (e.g., CD11b and CD66b upregulation and
CD62L shedding) and modified neutrophils' kinetic properties. Furthermore, each
TC-CM induced production of reactive oxygen species, expression of
proinflammatory and angiogenic mediators (CXCL8/IL-8, VEGF-A, and TNF-alpha), and
a release of matrix metalloproteinase 9 (MMP-9). Moreover, in TC patients, tumor
associated neutrophils correlated with larger tumor size. CONCLUSIONS: TC cell
lines produce soluble factors able to "educate" neutrophils toward an activated
functional state. These data will advance the understanding of the molecular and
cellular mechanisms of innate immunity in TC.
PMID- 29953506
TI - Climatic niche shift in the amphitropical disjunct grass Trichloris crinita.
AB - Plant species disjunctions have attracted the interest of ecologists for decades.
We investigated Trichloris crinita, a native C4 perennial grass with disjunct
distribution between subtropical regions of North and South America, testing the
hypothesis that the species has a similar realized climatic niche in both
subcontinents. The climatic niche of T. crinita in North and South America was
characterized and compared using presence records and five uncorrelated
bioclimatic variables selected according to their ecological importance for the
species. We used reciprocal modeling to make geographic projections of the
realized niche within each subcontinent. Niche overlap between T. crinita
distributions in North and South America was intermediate for the individual
climatic variables and the multivariate space. In all cases the test of
equivalence between climates inhabited by T. crinita indicated that the realized
niche of the species differ significantly between subcontinents. Also, the
similarity test showed that in the majority of cases the realized niche in both
subcontinents was significantly different than that expected by chance. T.
crinita occupied a greater diversity of environments in South than in North
America, while in the latter its distribution was displaced to drier and warmer
environments. The modeled geographic distribution using the actual occurrences of
the species in North America did not accurately predict the distribution in South
America, and vice versa. Together, these results led us to reject the hypothesis
of similar niche of T. crinita in both subcontinents. This information may be
useful to manage restoration efforts by presenting the suitable areas and
climates for the species, and suggesting that translocation of individuals
between subcontinents could only be recommended with caution because introduced
genotypes can be potentially maladaptive, and could colonize sites actually not
occupied by the species within each subcontinent.
PMID- 29953507
TI - Aortic root evaluation prior to transcatheter aortic valve implantation
Correlation of manual and semi-automatic measurements.
AB - BACKGROUND: Pre-procedural TAVI planning requires highly sophisticated and time
consuming manual measurements performed by experienced readers. Semi-automatic
software may assist with partial automation of assessment of multiple parameters.
The aim of this study was to evaluate differences between manual and semi
automatic measurements in terms of agreement and time. METHODS: One hundred and
twenty TAVI candidates referred for the retrospectively ECG-gated CTA (2nd and
3rd generation dual source CT) were evaluated. Fully manual and semi-automatic
measurements of fourteen aortic root parameters were assessed in the 20% phase of
the R-R interval. Reading time was compared using paired samples t-test. Inter
software agreement was calculated using the Intraclass correlation coefficient
(ICC) in a 2-way mixed effects model. Differences between manual and semi
automatic measurements were evaluated using Bland-Altman analysis. RESULTS: The
time needed for evaluation using semi-automatic assessment (3 min 24 s +/- 1 min
7 s) was significantly lower (p<0.001) compared to a fully manual approach (6 min
31 sec +/- 1 min 1 sec). Excellent inter-software agreement was found (ICC = 0.93
+/- 0.0; range:0.90-0.95). The same prosthesis size from manual and semi
automatic measurements was selected in 92% of cases, when sizing was based on
annular area. Prosthesis sizing based on annular short diameter and perimeter
agreed in 99% and 96% cases, respectively. CONCLUSION: Use of semi-automatic
software in pre-TAVI evaluation results in comparable results in respect of
measurements and selected valve prosthesis size, while necessary reading time is
significantly lower.
PMID- 29953508
TI - Pro-inflammatory cytokines attenuate glucose-stimulated insulin secretion from
INS-1E insulinoma cells by restricting mitochondrial pyruvate oxidation capacity
Novel mechanistic insight from real-time analysis of oxidative phosphorylation.
AB - Pro-inflammatory cytokines cause pancreatic beta cell failure during the
development of type 2 diabetes. This beta cell failure associates with
mitochondrial dysfunction, but the precise effects of cytokines on mitochondrial
respiration remain unclear. To test the hypothesis that pro-inflammatory
cytokines impair glucose-stimulated insulin secretion (GSIS) by inhibiting
oxidative ATP synthesis, we probed insulin release and real-time mitochondrial
respiration in rat INS-1E insulinoma cells that were exposed to a combination of
2 ng/mL interleukin-1-beta and 50 ng/mL interferon-gamma. We show that 24-h
exposure to these cytokines dampens both glucose- and pyruvate-stimulated insulin
secretion (P < 0.0001 and P < 0.05, respectively), but does not affect KCl
induced insulin release. Mirroring secretory defects, glucose- and pyruvate
stimulated mitochondrial respiration are lowered after cytokine exposure (P <
0.01). Further analysis confirms that cytokine-induced mitochondrial respiratory
defects occur irrespective of whether fuel oxidation is coupled to, or uncoupled
from, ATP synthesis. These observations demonstrate that pro-inflammatory
cytokines attenuate GSIS by restricting mitochondrial pyruvate oxidation
capacity. Interleukin-1-beta and interferon-gamma also increase mitochondrial
superoxide levels (P < 0.05), which may reinforce the inhibition of pyruvate
oxidation, and cause a modest (20%) but significant (P < 0.01) loss of INS-1E
cells. Cytokine-induced INS-1E cell failure is insensitive to palmitoleate and
linoleate, which is at odds with the cytoprotection offered by unsaturated fatty
acids against harm caused by nutrient excess. Our data disclose a mitochondrial
mechanism for cytokine-impaired GSIS in INS-1E cells, and suggest that
inflammatory and nutrient-related beta cell failure emerge, at least partly,
through distinct paths.
PMID- 29953509
TI - The association between new onset atrial fibrillation and incident cancer-A
nationwide cohort study.
AB - A recent analysis showed an association with new onset atrial fibrillation (NOAF)
and incident cancer among women. We aimed to examine the risk of cancer among
patients with NOAF in general population. A retrospective cohort of 5130 patients
with NOAF was identified from a random sample of one million subjects between
2005 and 2010 from Taiwan National Health Insurance Research Database. The
standard incidence ratio of incident cancer and hazard ratios were calculated by
modeling cumulative incidence with competing risk of death. During a mean follow
up duration of 3.4 years, 330 patients developed cancer. The standard incidence
ratio of all malignancies was 1.41 (95% confidence interval 1.26-1.57),
suggesting a 41% increase in cancer risk compared with the general population.
The risk of cancer was higher among men or the elderly with NOAF after adjusting
for confounding factors and after considering the competing risk of death. The
risk of cancer was not associated with CHA2DS2-VASc score (p = 0.32) among
patients with NOAF. In conclusion, patients with NOAF were associated with a
higher risk of cancer. Within this group, the risk of ischemic stroke (in terms
of CHADS2-VASc score) did not reflect the risk of incident cancer.
PMID- 29953510
TI - A case for revisiting peer review: Implications for professional self-regulation
and quality improvement.
AB - BACKGROUND: Quality improvement in healthcare has often been promoted as
different from and more valuable than peer review and other professional self
regulation processes. In spite of attempts to harmonize these two approaches, the
perception of dichotomous opposition has persisted. A sequence of events in the
troubled California prison system fortuitously isolated workforce interventions
from more typical quality improvement interventions. Our objectives were to (1)
evaluate the relative contributions of professional accountability and quality
improvement interventions to an observed decrease in population mortality and (2)
explore the organizational dynamics that potentiated positive outcomes. METHODS:
Our retrospective mixed-methods case study correlated time-series analysis of
mortality with the timing of reform interventions. Quantitative and qualitative
evidence was drawn from court documents, public use files, internal databases,
and other archival documents. RESULTS: Change point analysis reveals with 98%
confidence that a significant improvement in age-adjusted natural mortality
occurred in 2007, decreasing from 138.7 per 100,000 in the 1998-2006 period to
106.4 in the 2007-2009 period. The improvement in mortality occurred after
implementation of accountability processes, prior to implementation of quality
improvement interventions. Archival evidence supports the positive impact of
physician competency assessments, robust peer review, and replacement of problem
physicians. CONCLUSIONS: Our analysis suggests that workforce accountability
provides a critical quality safeguard, and its neglect in scholarship and
practice is unjustified. As with quality improvement, effective professional self
regulation requires systemic implementation of enabling policies, processes, and
staff resources. The study adds to evidence that the distribution of physician
performance contains a heterogeneous left skew of dyscompetence that is
associated with significant harm and suggests that professional self-regulation
processes such as peer review can reduce that harm. Beyond their responsibility
for direct harm, dyscompetent professionals can have negative impacts on group
performance. The optimal integration of professional accountability and quality
improvement systems merits further investigation.
PMID- 29953511
TI - The role of self-objectification and women's blame, sympathy, and support for a
rape victim.
AB - Sexual aggression is prevalent and damaging in our culture, and sources of
support or blame following an attack of this kind can be important influences on
the recovery process. This pair of studies investigate the nature of women's
blame reactions towards survivors of sexual aggression, as well as the potential
for provision of sympathy and support. Specifically, we focused on the previously
neglected role of female self-objectification. It was expected that increased
self-objectification would lead to decreased sympathy and support, and more rape
victim blame. However, results of Study 1 showed that chronic self
objectification was actually related to higher levels of sympathy and support for
a rape victim. Study two built upon the limitations of study one, and examined
similar questions. It was expected that women who engaged in greater self
objectification would again show greater sympathy and support for the victim,
replicating study one's results, and this was supported with a different scale.
The overall relationship between self-objectification and sympathy and support
was driven by body-relevant control beliefs. Implications and future directions
are discussed.
PMID- 29953512
TI - Biomechanical simulation of correcting primary unilateral cleft lip nasal
deformity.
AB - For better outcomes of the primary correction of cleft lip nasal deformity, it is
important to clarify the specific morphological and biomechanical consequences of
major surgical maneuvers during cleft lip nose correction. In this study, a
finite element model was established basing on the micro-MRI imaging of an infant
specimen with unilateral complete cleft lip deformity. Alar base adduction was
simulated as a medially-directed force on the lateral crus (F1); columella
straightening was simulated as a laterally-directed force on the medial crus
(F2); and nasal tip enhancement was simulated as an anteriorly-directed force on
the intermediate crus (F3). The deformation and stress distribution consequent to
each force vector or different force combinations were analyzed in details. Our
biomechnical analyses suggested that W?when loaded alone, the three forces
generated disparate morphological changes. The combination of different force
loadings generated obviously different outcomes. F3 generated the most intensive
stress when compared to F1 and F2. When F2 was loaded on top of F1-F3
combination, it further relieved nasal deviation without incurring significant
increase in stress. Our simulation suggested that alar base adduction, columella
straightening, and nasal tip elevation should all be included in a competent
cleft lip nose correction.
PMID- 29953513
TI - IDH1-mutated transgenic zebrafish lines: An in-vivo model for drug screening and
functional analysis.
AB - INTRODUCTION: The gene encoding isocitrate dehydrogenase 1 (IDH1) is frequently
mutated in several tumor types including gliomas. The most prevalent mutation in
gliomas is a missense mutation leading to a substitution of arginine with
histidine at the residue 132 (R132H). Wild type IDH1 catalyzes oxidative
decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) whereas mutant
IDH1 converts alpha-KG into D2-hydroxyglutarate (D2HG). Unfortunately, there are
few in vivo model systems for IDH-mutated tumors to study the effects of IDH1
mutations in tumor development. We have therefore created transgenic zebrafish
lines that express various IDH1 mutants. MATERIALS AND METHODS: IDH1 mutations
(IDH1R132H, IDH1R132C and loss-of-function mutation IDH1G70D), IDH1wildtype or
eGFP were cloned into constructs with several brain-specific promoters (Nestin,
Gfap or Gata2). These constructs were injected into fertilized zebrafish eggs at
the one-cell stage. RESULTS: In total more than ten transgenic zebrafish lines
expressing various brain-specific IDH1 mutations were created. A significant
increase in the level of D2HG was observed in all transgenic lines expressing
IDH1R132C or IDH1R132H, but not in any of the lines expressing IDH1wildtype,
IDH1G70D or eGFP. No differences in 5-hydroxymethyl cytosine and mature collagen
IV levels were observed between wildtype and mutant IDH1 transgenic fish. To our
surprise, we failed to identify any strong phenotype, despite increased levels of
the oncometabolite D2HG. No tumors were observed, even when backcrossing with
tp53-mutant fish which suggests that additional transforming events are required
for tumor formation. Elevated D2HG levels could be lowered by treatment of the
transgenic zebrafish with an inhibitor of mutant IDH1 activity. CONCLUSIONS: We
have generated a transgenic zebrafish model system for mutations in IDH1 that can
be used for functional analysis and drug screening. Our model systems help
understand the biology of IDH1 mutations and its role in tumor formation.
PMID- 29953514
TI - Association of nefopam use with postoperative nausea and vomiting in
gynecological patients receiving prophylactic ramosetron: A retrospective study.
AB - BACKGROUND: Postoperative nausea and vomiting (PONV) is a common adverse effect
of opioid-based intravenous patient-controlled analgesia (IV PCA). Nefopam has
been considered as a good candidate for inclusion in multimodal analgesia because
of its opioid sparing effect, but it can be emetic. This study aims to examine
whether the use of nefopam combined with fentanyl in IV PCA was associated with
the higher incidence of PONV in patients receiving prophylactic ramosetron after
gynecological surgery. METHODS: Data from 296 patients who underwent
gynecological surgery were retrospectively reviewed. The patients received IV PCA
containing either fentanyl 1500 MUg and ketorolac 90 mg (Group K) or fentanyl
1500 MUg and nefopam 80 mg (Group N). All patients in both groups received 0.3 mg
of ramosetron at the end of surgery. The primary outcome measure was the
incidence of PONV during the 3-day postoperative period. RESULTS: No difference
was observed in the incidence of PONV during the 3-day postoperative period
between the two groups. However, the incidence of nausea on postoperative day 2
was significantly higher in Group N (10.3%) than in Group K (2.8%) (P = 0.016).
Multivariable logistic regression analysis showed that the use of nefopam was not
associated with a higher incidence of PONV (adjusted odds ratio, 1.616; 95%
confidence interval, 0.952-2.743, P = 0.076). There were no differences in
postoperative pain scores between the two groups. CONCLUSION: The combined use of
nefopam with fentanyl in IV PCA was not associated with the higher incidence of
PONV compared with the use of ketorolac and fentanyl combination in patients who
received ramosetron as PONV prophylactic agent. However, prospective trials are
required for a confirmative conclusion.
PMID- 29953515
TI - Four-dimensional analysis by high-speed holographic imaging reveals a chiral
memory of sperm flagella.
AB - Here high-speed Digital Holographic Microscopy (DHM) records sperm flagellar
waveforms and swimming paths in 4 dimensions (X, Z, and t). We find flagellar
excursions into the Z-plane nearly as large as the envelope of the flagellar
waveform projected onto the XY-plane. These Z-plane excursions travel as waves
down the flagellum each beat cycle. DHM also tracks the heads of free-swimming
sperm and the dynamics and chirality of rolling of sperm around their long axis.
We find that mouse sperm roll CW at the maximum positive Z-plane excursion of the
head, then roll CCW at the subsequent maximum negative Z-plane excursion. This
alternating chirality of rolling indicates sperm have a chiral memory. Procrustes
alignments of path trajectories for sequences of roll-counterroll cycles show
that path chirality is always CW for the cells analyzed in this study. Human and
bull sperm lack distinguishable left and right surfaces, but DHM still indicates
coordination of Z-plane excursions and rolling events. We propose that sperm have
a chiral memory that resides in a hypothetical elastic linkage within the
flagellar machinery, which stores some of the torque required for a CW or CCW
roll to reuse in the following counter-roll. Separate mechanisms control path
chirality.
PMID- 29953516
TI - The ecology of medical care on the westernmost remote island, Yonaguni Island,
Japan: A cross-sectional study.
AB - Yonaguni Island is a remote and isolated westernmost island in Japan, which is
the fastest aging country in the world. This study evaluated the current status
of medical supply-and-demand on the island and compared these results with
previous surveys carried out in rural parts of Japan. This was a retrospective
cohort study conducted at the Yonaguni Municipal Clinic, the only medical
facility in Yonaguni Island. The participants were patients who visited the
clinic over one year, between July 2015 and June 2016. We calculated the rate per
1,000 persons per month of clinic visits, referrals to off-island medical
facilities (e.g., hospitals and specialist clinics), referrals to off-island
emergency departments, off-island hospitalizations after referral, home visits,
and overnight observations at the clinic. In total, 6,197 patients (males, 46.3%)
visited the clinic. The rate of clinic visits per 1,000 persons per month was
516.4 (Standard deviation [SD] 28.1, 95% confidence interval [CI]: 500.5-532.3).
The rate per 1,000 persons per month was 14.0 (SD 3.9, 95% CI: 11.8-16.2) for off
island referrals, 3.8 (SD 2.1, 95% CI: 2.6-5.0) for referrals to emergency
departments, 4.8 (SD 2.6, 95% CI: 3.3-6.2) for hospitalizations, and 3.2 (SD 1.7,
95% CI: 2.2-4.1) for home visits. The rate of clinic visits was higher in
Yonaguni Island than in other rural areas, although the rate of off-island
referrals was lower. There were no significant differences between the number of
referrals to emergency departments, hospitalizations, and home visits in Yonaguni
Island, in comparison to other studies. Our study showed that patients presenting
with emergencies had similar rates of healthcare-seeking behavior to those
reported in previous studies in Japan; however, the referral rate was lower. We
assessed the ecology of medical care in this district by evaluating patient
behavior on an isolated island where access to medical care is geographically
limited.
PMID- 29953517
TI - Personality and social support as determinants of entrepreneurial intention.
Gender differences in Italy.
AB - The interest in the promotion of entrepreneurship is significantly increasing,
particularly in those countries, such as Italy, that suffered during the recent
great economic recession and subsequently needed to revitalize their economy.
Entrepreneurial intention (EI) is a crucial stage in the entrepreneurial process
and represents the basis for consequential entrepreneurial actions. Several
research projects have sought to understand the antecedents of EI. This study,
using a situational approach, has investigated the personal and contextual
determinants of EI, exploring gender differences. In particular, the mediational
role of general self-efficacy between internal locus of control (LoC), self
regulation, and support from family and friends, on the one hand, and EI, on the
other hand, has been investigated. The study involved a sample of 658 Italian
participants, of which 319 were male and 339 were female. Data were collected
with a self-report on-line questionnaire and analysed with SPSS 23 and Mplus 7 to
test a multi-group structural equation model. The results showed that self
efficacy totally mediated the relationship between internal LoC, self-regulation
and EI. Moreover, it partially mediated the relationship between support from
family and friends and EI. All the relations were significant for both men and
women; however, our findings highlighted a stronger relationship between self
efficacy and EI for men, and between support from family and friends and both
self-efficacy and EI for women. Findings highlighted the role of contextual
characteristics in addition to personal ones in influencing EI and confirmed the
key mediational function of self-efficacy. As for gender, results suggested that
differences between men and women in relation to the entrepreneur role still
exist. Practical implications for trainers and educators are discussed.
PMID- 29953518
TI - APRI and FIB-4 in the evaluation of liver fibrosis in chronic hepatitis C
patients stratified by AST level.
AB - BACKGROUND AND AIM: The aspartate aminotransferase (AST)-to-platelet ratio index
(APRI) and fibrosis-4 index (FIB-4) are commonly used compound surrogates for
advanced fibrosis in chronic hepatitis C (CHC) patients. However, the use of APRI
and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact
of necroinflammatory activity on transaminases. We sought to investigate the
optimal cutoff values of the two compound surrogates for predicting cirrhosis
stratified by AST level. METHODS: This retrospective study enrolled 1716
treatment-naive CHC patients who underwent liver biopsy prior to interferon
therapy from 1997-2010. Fibrosis was scored according to the modified Knodell
classification. The upper limit for normal AST in our hospital is 37 IU/L. We
stratified the enrolled patients into the categories of AST<=37 IU/L (N = 132),
37148 IU/L (N = 346).
RESULTS: 436 patients had cirrhosis (F4). The area under receiver operating
characteristic (AUROC) analysis results distinguishing cirrhosis (F4) from non
cirrhosis (F0-F3) were 0.81 for APRI and 0.85 for FIB-4 in patients with AST<=37
IU/L; 0.71 for APRI and 0.72 for FIB-4 in patients with 37148 IU/L. The optimal cutoff values of APRI
and FIB-4 for the diagnosis of cirrhosis were 0.6 and 1.4, respectively, in
patients with AST<=37 IU/L; 1.1 and 2.2, respectively, in patients with
37148 IU/L. CONCLUSIONS: We
provide optimal cutoff values of both APRI and FIB-4 to predict cirrhosis
stratified by AST levels, which should be more feasible compared with the single
cutoff values proposed in previous studies.
PMID- 29953519
TI - Permeability enhancement of deep hole pre-splitting blasting in the low
permeability coal seam of the Nanting coal mine.
AB - To solve the hidden danger of high methane and low permeability gas in the coal
mining process, potentially affecting the safety production in an orderly way, we
propose the use of deep hole blasting technology to improve the permeability of
the coal seam gas drainage, increase the quantity and rate of extraction, and
reduce methane output. Taking the geological conditions of the 201 working
surface of Tingnan Coal Mine as an example, it is calculated that the single
drilled fracture crack extension range is 3.11~5.24 m according to the coal seam
deep-hole pre-splitting blasting joint mechanism and fracture propagation
mechanics model, providing a theoretical basis for choosing the appropriate hole
spacing. Using COMSOL simulation software to simulate the effective gas drainage
radius of a coal seam from a two-dimensional perspective on a single borehole
radial, the least squares fitting method was used to analyze the simulated data,
and obtained the effective drilling extraction radius after pre-split blasting in
a deep hole that is 3.6 m, which is in accordance with the theoretical
calculations. In order to obtain accurate and scientific calculations, Fast
lagrangian analysis of continua (FLAC3D) numerical simulation software was used.
After simulating the distribution of plastic zone between two blast holes at
different intervals from a three-dimensional angle, and evaluating the
development of cracks in the blasting hole, the white zone of the blasting space
was completely eliminated when the interval between blasting holes was 7 m, and
the cracks could be propagated throughout the surroundings. Therefore, a blasting
hole spacing of 7 m is optimal. On-site monitoring in the Nanting coal mine
showed that the quantity and rate of extraction of the single hole after pre
splitting blasting were 2.36 times and 1.62 times as much as before. By
integrating the borehole drainage amount and the optimized calculation equation,
it could be concluded that the permeability coefficient of the coal seam after
blasting was 7.78 times as much as before. The function of time-variated drilling
methane emission was obtained using multivariate statistical regressions based on
the on-site monitored borehole methane emission (qt), and the drilling limit
after pre-splitting blasting revealed that the limitation of methane extraction
volume was 5.27 times as much as before.
PMID- 29953520
TI - The effect of HIV infection on glycaemia and renal function in type 2 diabetic
patients.
AB - BACKGROUND: Infection with, and treatment of HIV is associated with effects on
glycaemia and renal function. The purpose of this study was therefore to compare
glycaemic control and albuminuria in HIV-positive and HIV-negative type 2
diabetic patients. MATERIALS AND METHODS: Diabetic patients with and without HIV
infection were recruited from a diabetic clinic at Chris Hani Baragwanath
Hospital in Soweto, South Africa. Data was collected on weight, height, HbA1c,
fasting glucose, urine albumin:creatinine ratio, HIV status, CD4 counts, viral
load and concomitant therapies. Multivariable regression analysis was used to
isolate the determinants of fasting glucose and HbA1c levels and risk factors for
albuminuria. RESULTS: Data were collected from 106 HIV-positive and 214 HIV
negative diabetics. All HIV infected subjects were receiving anti-retroviral
therapy. The determinants of fasting glucose levels (log) were HIV infection
(beta = 0.04, p = 0.01) and use of anti-hypertensive agents (beta = 0.07, p =
0.0006), whilst for HbA1c levels (log) they were HIV infection (beta = -0.03, p =
0.03), BMI (beta = 0.004, p = 0.0005), statin use (beta = 0.04, p = 0.002) and
glucose levels (beta = 0.01, p<0.0005). In HIV-positive subjects, CD4 counts were
negatively associated with glucose levels (beta = -0.0002, p = 0.03). The risk
factors for albuminuria were (odds ratio [95% CIs]) dyslipidaemia (1.94 [1.09,
3.44], p = 0.02) and HbA1c levels (1.24 [1.12, 1.38], p<0.0001). DISCUSSION:
These data suggest that glycaemic control is worse in type 2 diabetic subjects
with HIV infection and that HbA1c underestimates glycaemia in these patients.
Albuminuria was not associated with HIV-positivity. The negative relationship of
CD4 counts with glucose levels may reflect viral removal and easing of the
associated inflammatory response. It is possible that the association of statin
and anti-hypertensive therapies with high HbA1c and glucose levels, respectively,
is due to such therapies being given largely to subjects with poor glycaemic
control.
PMID- 29953521
TI - Tissue and serum expression of TGM-3 may be prognostic marker in patients of oral
squamous cell carcinoma undergoing chemo-radiotherapy.
AB - Radioresistance is one of the main determinants of treatment outcome in oral
squamous cell carcinoma (OSCC), but its prediction is difficult. Several authors
aimed to establish radioresistant OSCC cell lines to identify genes with altered
expression in response to radioresistance. The development of OSCC is a multistep
carcinogenic process that includes activation of several oncogenes and
inactivation of tumour suppressor genes. TGM-3 is a tumour suppressor gene and
contributes to carcinogenesis process. The aim of this study was to estimate
serum and tissue expression of TGM-3 and its correlation with clinico
pathological factors and overall survival in patients of OSCC undergoing chemo
radiotherapy. Tissue expression was observed in formalin fixed tissue biopsies of
96 cases of OSCC and 32 healthy controls were subjected to immunohistochemistry
(IHC) by using antibody against TGM-3 and serum level was estimated by ELISA
method. mRNA expression was determined by using Real-Time PCR. Patients were
followed for 2 year for chemo radiotherapy response. In OSCC, 76.70% cases and in
controls 90.62% were positive for TGM-3 IHC expression. TGM-3 expression was
cytoplasmic and nuclear staining expressed in keratinized layer, stratum
granulosum and stratum spinosum in controls and tumour cells. Mean serum TGM-3 in
pre chemo-radiotherapy OSCC cases were 1304.83+/-573.55, post chemo-radiotherapy
samples were 1530.64+/-669.33 and controls were 1869.16+/-1377.36, but difference
was significant in pre chemo-radiotherapy samples as compared to controls
(p<0.018). This finding was also confirmed by real- time PCR analysis in which
down regulation (-7.92 fold change) of TGM-3 in OSCC as compared to controls. TGM
3 expression was significantly associated with response to chemo-radiotherapy
treatment (p<0.007) and overall survival (p<0.015). Patents having higher level
of TGM-3 expression have good response to chemo-radiotherapy and also have better
overall survival. TGM-3 may serve as a candidate biomarker for responsiveness to
chemo-radiotherapy treatment in OSCC patients.
PMID- 29953522
TI - High content, high-throughput screening for small molecule inducers of NF-kappaB
translocation.
AB - NF-kappaB is an important mediator of immune activity and its activation is
essential in mounting immune response to pathogens. Here, we describe the
optimization and implementation of a high-throughput screening platform that
utilizes high content imaging and analysis to monitor NF-kappaB nuclear
translocation. We screened 38,991 compounds from three different small molecule
libraries and identified 103 compound as hits; 31% of these were active in a dose
response assay. Several of the molecules lacked cytotoxicity or had a selectivity
index of more than 2-fold. Our image-based approach provides an important first
step towards identifying small molecules with immunomodulatory activity.
PMID- 29953523
TI - Vaccination of koalas (Phascolarctos cinereus) against Chlamydia pecorum using
synthetic peptides derived from the major outer membrane protein.
AB - Chlamydia pecorum is a mucosal infection, which causes debilitating disease of
the urinary tract, reproductive tract and ocular sites of koalas (Phascolarctos
cinereus). While antibiotics are available for treatment, they are detrimental to
the koalas' gastrointestinal tract microflora leaving the implementation of a
vaccine as an ideal option for the long-term management of koala populations. We
have previously reported on the successes of an anti-chlamydial recombinant major
outer membrane protein (rMOMP) vaccine however, recombinant protein based
vaccines are not ideal candidates for scale up from the research level to small
medium production level for wider usage. Peptide based vaccines are a promising
area for vaccine development, because peptides are stable, cost effective and
easily produced. In this current study, we assessed, for the first time, the
immune responses to a synthetic peptide based anti-chlamydial vaccine in koalas.
Five healthy male koalas were vaccinated with two synthetic peptides derived from
C. pecorum MOMP and another five healthy male koalas were vaccinated with full
length recombinant C. pecorum MOMP (genotype G). Systemic (IgG) and mucosal (IgA)
antibodies were quantified and pre-vaccination levels compared to post
vaccination levels (12 and 26 weeks). MOMP-peptide vaccinated koalas produced
Chlamydia-specific IgG and IgA antibodies, which were able to recognise not only
the genotype used in the vaccination, but also MOMPs from several other koala C.
pecorum genotypes. In addition, IgA antibodies induced at the ocular site not
only recognised recombinant MOMP protein but also, whole native chlamydial
elementary bodies. Interestingly, some MOMP-peptide vaccinated koalas showed a
stronger and more sustained vaccine-induced mucosal IgA antibody response than
observed in MOMP-protein vaccinated koalas. These results demonstrate that a
synthetic MOMP peptide based vaccine is capable of inducing a Chlamydia-specific
antibody response in koalas and is a promising candidate for future vaccine
development.
PMID- 29953524
TI - A non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6,
is associated with heroin addiction.
AB - Dysregulation of the stress response is implicated in drug addiction; therefore,
polymorphisms in stress-related genes may be involved in this disease. An
analysis was performed to identify associations between variants in 11 stress
related genes, selected a priori, and heroin addiction. Two discovery samples of
American subjects of European descent (EA, n = 601) and of African Americans (AA,
n = 400) were analyzed separately. Ancestry was verified by principal component
analysis. Final sets of 414 (EA) and 562 (AA) variants were analyzed after
filtering of 846 high-quality variants. The main result was an association of a
non-coding SNP rs255105 in the CRH (CRF) receptor 2 gene (CRHR2), in the
discovery EA sample (Pnominal = .00006; OR = 2.1; 95% CI 1.4-3.1). The
association signal remained significant after permutation-based multiple testing
correction. The result was corroborated by an independent EA case sample (n =
364). Bioinformatics analysis revealed that SNP rs255105 is associated with the
expression of a downstream long intergenic non-coding RNA (lincRNA) gene
AC005154.6. AC005154.6 is highly expressed in the pituitary but its functions are
unknown. LincRNAs have been previously associated with adaptive behavior, PTSD,
and alcohol addiction. Further studies are warranted to corroborate the
association results and to assess the potential relevance of this lincRNA to
addiction and other stress-related disorders.
PMID- 29953525
TI - A mechanically based magneto-inductive transmitter with electrically modulated
reluctance.
AB - Magneto-inductive (MI) communication is a viable technology for wireless
communications in underwater and underground environments. In this paper, a new
design for an MI transmitter is presented. Unlike conventional MI transmitters
that utilize coiled loops or solenoids to generate magnetic fields, we
demonstrate the feasibility and advantages of using a rotating permanent magnet.
We also present and experimentally verify a modulation technique that does not
involve changing the rotational speed of the magnet. By electrically changing the
permeability of a surrounding shield, the fields from the rotating magnet are
amplitude modulated. Our findings suggest that increased efficiency and bandwidth
can be realized compared to conventional MI transmitters.
PMID- 29953526
TI - Developing a comprehensive, culturally sensitive conceptual framework of health
domains in Singapore.
AB - The increasing focus of healthcare systems worldwide on long-term care highlights
the need for culturally sensitive Health-Related Quality of Life instruments to
accurately capture perceived health of various populations. Such instruments
require a contextualized conceptual framework of health domains, which is lacking
in some socio-cultural contexts. We developed a comprehensive and culturally
sensitive conceptual framework of health domains relevant to the Singaporean
population. We recruited Singaporeans/ permanent residents, English/ Chinese
speaking, with/ without chronic illnesses to participate in focus group
discussions (FGDs) and in-depth interviews (IDIs). We elicited health areas
participants perceived to be important for them to be happy and satisfied with
life. To encourage spontaneous emergence of themes, we did not specify any aspect
beyond the broad domains of Physical, Mental, and Social health so as not to
limit the emergence of new themes. Themes from the transcripts were distilled
through open coding (two independent coders), then classified into more abstract
domains (each transcript coded independently by two coders from a pool of six
coders). From October 2013 to August 2014, 121 members of the general public
participated in 18 FGDs and 13 IDIs (44.6% males, mean age: 53.3 years 77%
Chinese, 9% Malay, 12% Indian, 63% with chronic illness) while 13 healthcare
workers participated as patient-proxies in three FGDs. Thematic analysis
identified 27 domains. The 15 physical domains included physical appearance,
energy, physical fitness, and health and resistance to illness. The nine mental
domains included emotions, self-esteem, and personal freedom. The three social
domains were social contact, social relationships, and social roles. This
conceptual framework reflected physical, mental, and social dimensions of well
being, suggesting that the Singapore population's views on health support the
World Health Organization's definition of health as "a state of complete
physical, mental and social well-being and not merely the absence of disease or
infirmity".
PMID- 29953527
TI - Clinical usefulness of library and information services in Japan: The detailed
use and value of information in clinical settings.
AB - OBJECTIVES: Considering that there is a lack of evidence regarding the
contribution of library and information services to evidence-based medicine in
actual clinical practice in Japan, the purpose of the study is to explore the
current status of use and value of library and information services in clinical
settings to examine the usefulness of information in implementing evidence-based
medicine (EBM) into practice. METHODS: A Web-based survey was conducted at seven
sites (hospitals with 300-1,200 beds) and interviews conducted at five sites to
investigate information behavior among health professionals (physicians,
residents, and nurses) in 2016, replicating the Value Study carried out in the
United States in 2010 and 2011. Using a critical incident technique, respondents
answered questions about their information topics, information resources used,
search location, access points, and evaluation of the information. RESULTS:
Analysis from 598 valid responses (275 physicians, 55 residents, and 268 nurses)
revealed the characteristics of information use and recognition of the value of
information. Physicians and residents showed their information needs regarding
clinical care using PubMed (80.4%, 65.5%), Ichushi-Web (61.8%, 63.6%), and
UpToDate (40.4%, 65.5%). While physicians rely more on electronic journals
(37.8%), residents use more hybrid resources including Japanese print books
(38.2%) and online books (30.9% for Japanese, 32.7% for English) to confirm their
knowledge. Nurses need more information close to patients and explore a wider
variety of information resources such as Japanese print books (60.4%), Ichushi
Web (40.3%), Japanese online books (20.5%), and websites of academic
organizations (19.0%). Although the overall recognition of the value of
information was relatively modest, concrete changes in clinical practice were
found in some areas. Environments with insufficient information and availability
of electronic resources should be improved to increase the use of library and
information services for implementing EBM.
PMID- 29953528
TI - Thrombodynamics-A new global hemostasis assay for heparin monitoring in patients
under the anticoagulant treatment.
AB - BACKGROUND: Heparin therapy and prophylaxis may be accompanied by bleeding and
thrombotic complications due to individual responses to treatment. Dosage control
based on standard laboratory assays poorly reflects the effect of the therapy.
The aim of our work was to compare the heparin sensitivity of new thrombodynamics
(TD) assay with sensitivity of other standard and global coagulation tests
available to date. STUDY POPULATION AND METHODS: A total of 296 patients with
high risk of venous thromboembolism (deep vein thrombosis (DVT), early
postoperative period, hemoblastosis) were enrolled in the study. We used a case
crossover design to evaluate the sensitivity of new thrombodynamics assay (TD) to
the hemostatic state before and after unfractionated heparin (UFH) and low
molecular-weight heparin (LMWH) therapy/prophylaxis and to compare it with the
activated partial thromboplastin time (APTT), anti-Xa activity test, thrombin
generation test (TGT) and thromboelastography (TEG). A receiver operating
characteristic (ROC) curve analysis was used to evaluate changes before and after
heparin prophylaxis and therapy. Blood was sampled before heparin injection, at
the time of maximal blood heparin concentration and before the next injection.
RESULTS: Hypercoagulation before the start of heparin treatment was detected by
TD, TGT and TEG but not by APTT. The area under the ROC curve (AUC) was maximal
for TD and anti-Xa, intermediate for TGT and TEG and minimal for APTT.
CONCLUSIONS: These results indicate that TD has a high sensitivity to the effects
of UFH and LMWH after both prophylactic and therapeutic regimes and may be used
for heparin monitoring.
PMID- 29953529
TI - Soot and the city: Evaluating the impacts of Clean Heat policies on
indoor/outdoor air quality in New York City apartments.
AB - New York City has had a long history of implementing local policies to reduce air
pollution. Enacted as a part of PlaNYC, the Clean Heat policies aim to lower
wintertime ambient air pollution by phasing out dirty No. 6 heating fuel oil and
transitioning to comparatively cleaner No. 4, No. 2, or natural gas. This study
evaluates the impacts of policies on ambient air pollution and, given that people
spend the majority of their time inside, importantly, indoor air pollution. Using
a natural experiment, we evaluate the effects of the policies by measuring
average two-week levels of indoor and outdoor black carbon (BC) and fine
particulate matter (PM2.5) in 48 upper Manhattan apartments in successive winter
heating seasons before and after mandated fuel transition. We failed to observe
systematic improvements in indoor BC and PM2.5 concentrations in follow-up.
However, outdoor levels of PM2.5 did improve, with statistical differences
observed among buildings converting to the cleanest fuels. Non-statistical
improvements were observed for outdoor BC. However, when accounting for
meteorological differences, apartment characteristics, and behavioral patterns
that may have influenced air pollution measurements, these differences were not
significant. The study results have important policy and equity implications
considering the differential improvements in air quality by conversion to No. 4
oil as compared to the cleaner No. 2 oil and natural gas.
PMID- 29953530
TI - Climate-driven changes of riparian plant functional types in permanent headwater
streams. Implications for stream food webs.
AB - Little is known regarding consequences of climate change on riparian plant
functional types (PFTs) related to leaf traits, with putative domino effects on
stream food webs, plausible even if the tipping point of stream-desiccation is
not reached. We hypothesized that, as stream food-webs are highly dependent on
riparian subsidies, climate change might alter PFTs to the point of weakening
terrestrial-aquatic linkages. We conducted a gradient analysis to assess the
relative effects of climate, soil and riparian physical characteristics on PFTs.
If PFTs differ significantly in leaf traits and climate had major influences on
them, we could assume space-for-time interchangeability forward in time to
predict leaf traits changes, and consequences for stream food webs under future
climate change scenarios. Results indicated a clear distinction in leaf traits
among PFTs: woody deciduous plants showed leaf traits associated to high
decomposability and nutritional value for invertebrate shredders compared to
evergreen woody and giant graminoid groups. We found a prime role of climate
predicting changes in abundance and diversity of PFTs: 1) a warming and
precipitation-decline scenario, coupled with soil characteristics related to
aridification, would have detrimental effects on deciduous plants, while
fostering giant graminoids; 2) in a scenario of no precipitation-reduction in
wetter areas, warming might promote the expansion of evergreen to the detriment
of deciduous plants. In both scenarios the net outcome implies increasing
recalcitrance of leaf litter inputs, potentially weakening terrestrial-aquatic
linkages in headwater streams.
PMID- 29953531
TI - Changes in rhizosphere microbial communities in potted cucumber seedlings treated
with syringic acid.
AB - Phytotoxic effects of phenolic compounds have been extensively studied, but less
attention has been given to the effects of these compounds on soil microbial
communities, which are crucial to the productivity of agricultural systems.
Responses of cucumber rhizosphere bacterial and fungal communities to syringic
acid (SA), a phenolic compound with autotoxicity to cucumber, were analyzed by
high-throughput sequencing of 16S rRNA gene and internal transcribed spacer
amplicons. SA at the concentration of 0.1 MUmol g-1 soil changed rhizosphere
bacterial and fungal community compositions, decreased bacterial community
diversity but increased fungal community richness and diversity (P<0.05).
Moreover, SA increased the relative abundances of bacterial phylum Proteobacteria
and fungal classes Leotiomycetes, Pezizomycetes, Tremellomycetes and
Eurotiomycetes, but decreased the relative abundances of bacterial phylum
Firmicutes and fungal class Sordariomycetes (P<0.05). At the genus level, SA
decreased the relative abundances of microbial taxa with pathogen-antagonistic
and/or plant growth promoting potentials, such as Pseudomonas spp. (P<0.05). Real
time PCR validated that SA decreased cucumber rhizosphere Pseudomonas spp.
abundance (P<0.05). In vitro study showed that SA (0.01 to 10 mM) inhibited the
growth of a strain of Pseudomonas spp. with pathogen-antagonistic activities to
cucumber pathogen Fusarium oxysporum f.sp. cucumerinum Owen (P<0.05). Overall, SA
changed cucumber rhizosphere bacterial and fungal community compositions, which
may exert negative effects on cucumber seedling growth through inhibiting plant
beneficial microorganisms.
PMID- 29953532
TI - Outpatient rehabilitation resources and medical expenditure in children with
attention-deficit hyperactivity disorder in Taiwan.
AB - Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder
in children. This study investigated the use of rehabilitation treatment in
Taiwan. We selected children aged 3-12 years from the National Health Insurance
Research Database from 2008 to 2012 and included them in the analysis. The
children who received a diagnosis according to the International Classification
of Diseases, Ninth Revision, Clinical Modification were divided into two groups:
ADHD and non-ADHD. We used the chi-squared test, independent sample t test, and
multiple regression analysis to conduct the analysis. The utilisation of
rehabilitation resources was higher in the ADHD group than in the non-ADHD group.
The number of school-aged children with ADHD was higher than the number of
preschool-aged children (p < 0.001). The highest utilisation of rehabilitation
resources was observed in clinics (p < 0.001). In terms of region, Taipei
exhibited the highest utilisation of rehabilitation resources, and the East
exhibited the lowest resource utilisation (p < 0.001). Prediction of the use of
rehabilitation resources, average cost, average frequency of visits, and total
annual cost was affected by factors such as the average frequency of
rehabilitation use, demographic characteristics, and the hospital characteristics
and location (p < 0.001). The number of children with ADHD and rehabilitation use
are increasing yearly; however, limitations in payment restrict the growth of
rehabilitation resource use in hospitals. Supplementation of rehabilitation
resources at clinics accounts for more than 60%, however, the total annual cost
is less than what is observed for hospitals (p < 0.001). Policies should be
established to aid in the early detection and treatment of children with ADHD to
improve treatment outcomes and reduce the family burden and treatment expenditure
in the future.
PMID- 29953533
TI - Correction: Prognostic model for psychological outcomes in ambulatory surgery
patients: A prospective study using a structural equation modeling framework.
AB - [This corrects the article DOI: 10.1371/journal.pone.0193441.].
PMID- 29953534
TI - Human peptidergic nociceptive sensory neurons generated from human epidermal
neural crest stem cells (hEPI-NCSC).
AB - Here we provide new technology for generating human peptidergic nociceptive
sensory neurons in a straightforward and efficient way. The cellular source,
human epidermal neural crest stem cells (hEPI-NCSC), consists of multipotent
somatic stem cells that reside in the bulge of hair follicles. hEPI-NCSC and
primary sensory neurons have a common origin, the embryonic neural crest. For
directed differentiation, hEPI-NCSC were exposed to pertinent growth factors and
small molecules in order to modulate master signalling networks involved in
differentiation of neural crest cells into postmitotic peptidergic sensory
neurons during embryonic development. The neuronal populations were homogenous in
regard to antibody marker expression. Cells were immunoreactive for essential
master regulatory genes, including NGN1/2, SOX10, and BRN3a among others, and for
the pain-mediating genes substance P (SP), calcitonin gene related protein (CGRP)
and the TRPV1 channel. Approximately 30% of total cells responded to capsaicin,
indicating that they expressed an active TRPV1 channel. In summary, hEPI-NCSC are
a biologically relevant and easily available source of somatic stem cells for
generating human peptidergic nociceptive neurons without the need for genetic
manipulation and cell purification. As no analgesics exist that specifically
target TRPV1, a ready supply of high-quality human peptidergic nociceptive
sensory neurons could open the way for new approaches, in a biologically relevant
cellular context, to drug discovery and patient-specific disease modelling that
is aimed at pain control, and as such is highly desirable.
PMID- 29953536
TI - Do outpatient statins and ACEIs/ARBs have synergistic effects in reducing the
risk of pneumonia? A population-based case-control study.
AB - Whether statins and an angiotensin-converting enzyme inhibitors (ACEIs) /
angiotensin receptor blockors (ARBs) are associated with reduced risks of
infection events is still inconclusive. This study aimed to explore the risk of
hospitalization for pneumonia among patients who had received treatment with
ACEIs/ARBs and/or statins using a population-based dataset. This study included
19,281 patients as cases who were hospitalized for pneumonia and 19,281 controls.
We used a logistic regression to compute the odds ratio (OR) and 95% confidence
interval (CI) for having previously used statins or an ACEI/ ARB between patients
who were hospitalized for pneumonia treatment and controls. We found there were
significant associations between hospitalization for pneumonia and statin-only
users (p<0.001), ACEI/ARB-only users (p<0.001), and statin and ACEI/ARB users
(p<0.001). The logistic regression analysis suggested that statin-only users
(adjusted OR = 0.38, 95% CI = 0.34~0.43), ACEI/ARB-only users (adjusted OR =
0.86, 95% CI = 0.82~0.91), and statin and ACEI/ARB users (adjusted OR = 0.47, 95%
CI = 0.44~0.50) were all less likely to be hospitalized for pneumonia treatment
than were non-users. Furthermore, we found that statin-only users (adjusted OR =
0.44, 95% CI = 0.40~0.50) and statin and ACEI/ARB users (adjusted OR = 0.55, 95%
CI = 0.52~0.58) were less likely to be hospitalized for pneumonia treatment
compared to ACEI-only users. However, combined statin and ACEI/ARB users
(adjusted OR = 1.24, 95% CI = 1.10~1.40) were more likely to have been
hospitalized for pneumonia treatment compared to statin-only users. Although we
found use of both statins and ACEI/ARB were significantly associated with a lower
risk of pneumonia, the combination of the two medications did not provide
additional protection against pneumonia risk.
PMID- 29953535
TI - Assessing emotions conveyed and elicited by patient narratives and their impact
on intention to participate in colorectal cancer screening: A psychophysiological
investigation.
AB - In the context of colorectal cancer screening, we aimed to compare the
effectiveness of different emotion-laden narratives, to investigate the specific
emotions elicited at both subjective and physiological levels, and to test the
effects of emotions explicitly expressed by the narrative character. Study 1 used
a between-participants design comparing four conditions: relief-based narrative,
regret-based narrative, control (test-uptake only) narrative, and standard
invitation material (no-narrative condition). Study 2 used a mixed design, with
the narrative content as a within-participants factor and whether emotions were
expressed by the narrative character or not as between-participants factor. The
main outcome measures were: intention to undergo testing (Studies 1 and 2),
knowledge, risk perception, proportion of informed choices (Study 1), subjective
emotional responses, changes in skin conductance, heart rate, and corrugator
muscle activity (Study 2). In Study 1, relative to the non-narrative condition
(51%), only the relief-based narrative significantly increased intention to
undergo testing (86%). Relative to the standard invitation material, the
narrative conditions did not decrease knowledge, alter risk perception, or
decrease the proportion of informed choices. In Study 2, the relief-based
narrative elicited the lowest self-reported negative affect, and received greater
implicit attention, as suggested by the larger heart rate decrease. Making the
emotions experienced by the narrative character explicit decreased negative
affect, as indicated by the lower skin conductance and corrugator responses
during reading. Our findings provide support for the use of a relief-based
narrative with emotions expressed by the character in addition to the standard
information material to promote colorectal cancer screening.
PMID- 29953537
TI - Positive and negative adjustment in couples undergoing infertility treatment: The
impact of support exchange.
AB - BACKGROUND: Perceived social support relates to infertility-related distress in
couples undergoing assisted reproductive technology (ART) treatment. Studies
examining the effect of other support types on both positive and negative
adjustment among infertile couples are scarce or non-existent. Therefore, this
study investigated the effects of support receipt, provision, invisibility (the
discrepancy between one partner's received and the other partner's provided
support), and equity (the discrepancy between each partner's received and
provided support) on the positive (life purpose) and negative (depressive
symptoms) indices of well-being in couples undergoing ART treatment. METHODS:
Depressive symptoms (CES-D), life purpose (PIL), and social support (BSSS) were
assessed among 31 married couples (mean age 32.67 years) undergoing ART
treatment. Data were analyzed by applying the Actor-Partner-Interdependence Model
(APIM) using multilevel modeling. FINDINGS: Both receiving and providing support
had beneficial effects in women and men. However, sub-analysis showed differences
according to gender and the support exchange effects. Women reported higher
depression and lower life purpose but benefited more from support, and their well
being was more dependent on their own perception of support provision and
receipt. Men demonstrated higher adjustment to infertility but benefited less
from support, and their well-being was mostly correlated with supportive
behaviors of their wives. DISCUSSION: Adjustment mechanisms of women and men
undergoing ART treatment vary considerably; thus, gender should be taken into
consideration in interventions. Future studies should focus on costs/benefits and
gender differences of visible and invisible support in infertility settings.
PMID- 29953538
TI - Anti-inflammatory consequences of bile acid accumulation in virus-infected bile
duct ligated mice.
AB - Cholestatic patients exhibiting high bile acid serum levels were reported to be
more susceptible to bacterial and viral infections. Animal studies in bile duct
ligated (BDL) mice suggest that cholestasis leads to an aggravation of hepatic
bacterial infections. We have investigated the impact of cholestasis on mouse
cytomegalovirus (MCMV)-induced immune responses and viral replication. While MCMV
did not aggravate BDL-induced liver damage, BDL markedly reduced MCMV-triggered
chemokine expression and immune cell recruitment to the liver. MCMV-infected BDL
mice showed diminished trafficking of Ly6C+/F4/80+ myeloid cells and NK1.1+ NK
cells to the liver compared to MCMV infected control mice. Moreover, virus-driven
expression of CCL7, CCL12, CXCL9 and CXCL10 was clearly impaired in BDL- compared
to sham-operated mice. Furthermore, production of the anti-inflammatory cytokine
IL-10 was massively augmented in infected BDL mice. In contrast, intra- and
extrahepatic virus replication was unaltered in BDL-MCMV mice when compared to
sham-MCMV mice. Cholestasis in the BDL model severely impaired pathogen-induced
chemokine expression in the liver affecting CCR2- and CXCR3-dependent cell
trafficking. Cholestasis resulted in reduced recruitment of inflammatory
monocytes and NK cells to the liver.
PMID- 29953539
TI - The inclusion of hyoid muscles improve moment generating capacity and dynamic
simulations in musculoskeletal models of the head and neck.
AB - OpenSim musculoskeletal models of the head and neck can provide information about
muscle activity and the response of the head and neck to a variety of situations.
Previous models report weak flexion strength, which is partially due to lacking
moment generating capacity in the upper cervical spine. Previous models have also
lacked realistic hyoid muscles, which have the capability to improve flexion
strength and control in the upper cervical spine. Suprahyoid and infrahyoid
muscles were incorporated in an OpenSim musculoskeletal model of the head and
neck. This model was based on previous OpenSim models, and now includes hyoid
muscles and passive elements. The moment generating capacity of the model was
tested by simulating physical experiments in the OpenSim environment. The flexor
and extensor muscle strengths were scaled to match static experimental results.
Models with and without hyoid muscles were used to simulate experimentally
captured motions, and the need for reserve actuators was evaluated. The addition
of hyoid muscles greatly increased flexion strength, and the model is the first
of its kind to have realistic strength values in all directions. Less reserve
actuator moment was required to simulate real motions with the addition of hyoid
muscles. Several additional ways of improving flexion strength were investigated.
Hyoid muscles add control and strength to OpenSim musculoskeletal models of the
head and neck and improve simulations of head and neck movements.
PMID- 29953540
TI - Biology must develop herd immunity against bad-actor molecules.
PMID- 29953541
TI - Correction: Performance of next-generation sequencing on small tumor specimens
and/or low tumor content samples using a commercially available platform.
AB - [This corrects the article DOI: 10.1371/journal.pone.0196556.].
PMID- 29953542
TI - Direct cell-to-cell transmission of respiratory viruses: The fast lanes.
PMID- 29953543
TI - Crystal structure of the C-terminal four-helix bundle of the potassium channel
KCa3.1.
AB - KCa3.1 (also known as SK4 or IK1) is a mammalian intermediate-conductance
potassium channel that plays a critical role in the activation of T cells, B
cells, and mast cells, effluxing potassium ions to maintain a negative membrane
potential for influxing calcium ions. KCa3.1 shares primary sequence similarity
with three other (low-conductance) potassium channels: KCa2.1, KCa2.2, and KCa2.3
(also known as SK1-3). These four homotetrameric channels bind calmodulin (CaM)
in the cytoplasmic region, and calcium binding to CaM triggers channel
activation. Unique to KCa3.1, activation also requires phosphorylation of a
single histidine residue, His358, in the cytoplasmic region, which relieves
copper-mediated inhibition of the channel. Near the cytoplasmic C-terminus of
KCa3.1 (and KCa2.1-2.3), secondary-structure analysis predicts the presence of a
coiled-coil/heptad repeat. Here, we report the crystal structure of the C
terminal coiled-coil region of KCa3.1, which forms a parallel four-helix bundle,
consistent with the tetrameric nature of the channel. Interestingly, the four
copies of a histidine residue, His389, in an 'a' position within the heptad
repeat, are observed to bind a copper ion along the four-fold axis of the bundle.
These results suggest that His358, the inhibitory histidine in KCa3.1, might
coordinate a copper ion through a similar binding mode.
PMID- 29953545
TI - Correction: Symbolic universes between present and future of Europe. First
results of the map of European societies' cultural milieu.
AB - [This corrects the article DOI: 10.1371/journal.pone.0189885.].
PMID- 29953544
TI - Methyl-CpG-binding (SmMBD2/3) and chromobox (SmCBX) proteins are required for
neoblast proliferation and oviposition in the parasitic blood fluke Schistosoma
mansoni.
AB - While schistosomiasis remains a significant health problem in low to middle
income countries, it also represents a recently recognised threat to more
economically-developed regions. Until a vaccine is developed, this neglected
infectious disease is primarily controlled by praziquantel, a drug with a
currently unknown mechanism of action. By further elucidating how Schistosoma
molecular components cooperate to regulate parasite developmental processes, next
generation targets will be identified. Here, we continue our studies on
schistosome epigenetic participants and characterise the function of a DNA
methylation reader, the Schistosoma mansoni methyl-CpG-binding domain protein
(SmMBD2/3). Firstly, we demonstrate that SmMBD2/3 contains amino acid features
essential for 5-methyl cytosine (5mC) binding and illustrate that adult
schistosome nuclear extracts (females > males) contain this activity. We
subsequently show that SmMBD2/3 translocates into nuclear compartments of
transfected murine NIH-3T3 fibroblasts and recombinant SmMBD2/3 exhibits 5mC
binding activity. Secondly, using a yeast-two hybrid (Y2H) screen, we show that
SmMBD2/3 interacts with the chromo shadow domain (CSD) of an epigenetic adaptor,
S. mansoni chromobox protein (SmCBX). Moreover, fluorescent in situ hybridisation
(FISH) mediated co-localisation of Smmbd2/3 and Smcbx to mesenchymal cells as
well as somatic- and reproductive- stem cells confirms the Y2H results and
demonstrates that these interacting partners are ubiquitously expressed and found
within both differentiated as well as proliferating cells. Finally, using RNA
interference, we reveal that depletion of Smmbd2/3 or Smcbx in adult females
leads to significant reductions (46-58%) in the number of proliferating somatic
stem cells (PSCs or neoblasts) as well as in the quantity of in vitro laid eggs.
Collectively, these results further expand upon the schistosome components
involved in epigenetic processes and suggest that pharmacological inhibition of
SmMBD2/3 and/or SmCBX biology could prove useful in the development of future
schistosomiasis control strategies.
PMID- 29953546
TI - Interventions to reduce risk for sexually transmitted infections in adolescents:
A meta-analysis of trials, 2008-2016.
AB - BACKGROUND: Numerous studies have evaluated the efficacy of interventions to
reduce risk for sexually transmitted infections in adolescents in recent years,
but their global effects remain unknown since 2008, the last date of a
comprehensive review of prior studies. AIMS: This study aims at evaluating the
efficacy of interventions to promote sexual health, reduce STIs and unplanned
pregnancies targeted to adolescents available after 2008; and analyzing the
moderators of their global efficacy. METHODS: We searched electronic databases
and manual searches of some journals focused on STIs in May 2016. The studies
evaluated the efficacy of interventions to reduce sexual risk in adolescents (age
range: 11-19) anywhere in the world. Effect size of the relevant outcomes for
sexual risk was calculated for every study. Analyses incorporated random-effect
assumptions for each outcome. The homogeneity in the results was examined with
the I2 statistic and its associated 95% confident interval. RESULTS: Data from 63
studies (59,795 participants) were analyzed for behavioral and non-behavioral
outcomes. In the short term, interventions had a positive impact in sexual health
related knowledge (Hedges'g = 1.01), attitudes (g = 0.29), self-efficacy toward
condom use (g = 0.22), intention to refuse sex (g = 0.56), condom use intention
(g = 0.46), and condom use (g = 0.38). In the medium term, positive effects
observed at the short-term were maintained, although effect size significantly
decreased in all variables. In the long term, interventions improved condom use
(g = 0.47). Moderators of the efficacy are discussed. CONCLUSIONS: Sexual health
promotion interventions are effective to promote sexual health through increasing
condom use. Effects on non-behavioral variables tend to decrease over time, while
condom use increased in the long-term. Interventions should focus on the long
term efficacy, especially in behavioral and biological measures.
PMID- 29953548
TI - The effects of genetic variation and environmental factors on rhynchophylline and
isorhynchophylline in Uncaria macrophylla Wall. from different populations in
China.
AB - Uncaria macrophylla Wall. is an important Chinese medicinal herb. Rhynchophylline
(RIN) and isorhynchophylline (IRN) are its major active compounds. We
investigated the influence of genetic differentiation and environmental factors
on the RIN and IRN to find the main influencing factors of their contents and lay
the foundation for the following cultivation and breeding. We used inter-simple
sequence repeat (ISSR) markers to investigate the genetic diversity, and high
performance liquid chromatography (HPLC) to measure the contents of RIN and IRN
in 200 samples of U. macrophylla obtained from nine natural populations, and then
to analyze the correlation between genetic differentiation, environmental factors
of sampling sites and the contents of RIN and IRN. We found that High intra
population (80.05%) and low inter-population (19.95%) genetic diversity existed
in the samples of U. macrophylla. To some extent, genetic differentiation and the
contents of RIN and IRN had correlation in individual populations (such as JH,
MH, XM, and ML). The RIN and IRN contents were significant negatively correlated
with the precipitation in May (RIRN = -0.771, p = 0.015) and June (RRIN = -0.814,
p = 0.008; RIRN = -0.921, p = 0.000), indicating that precipitation was the main
affecting factor of their contents. Interestingly, the analysis results showed
that the RIN content had a significant positive correlation (r = 0.585, p =
0.000) with the IRN content (they are isomers); the proportion of RIN had a
significant negative correlation with the sum of the two (r = -0.390, p<0.0001),
while the proportion of IRN had a significant positive correlation (r = 0.390,
p<0.0001). It meant that, with the total quantity of the two compounds increased,
the proportion of RIN decreased and the proportion of IRN increased, illustrating
that their conversion exist some regularity. Moreover, the content ratio of RIN
and IRN was significant positively correlated with the January precipitation (r =
0.716, p = 0.030), implying that January may be the key period for the mutual
transformation of RIN and IRN.
PMID- 29953547
TI - Randomized, placebo controlled phase I trial of safety, pharmacokinetics,
pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel
vaginal rings in women.
AB - To prevent the global health burdens of human immunodeficiency virus [HIV] and
unintended/mistimed pregnancies, we developed an intravaginal ring [IVR] that
delivers tenofovir [TFV] at ~10mg/day alone or with levonorgestrel [LNG] at
~20MUg/day for 90 days. We present safety, pharmacokinetics, pharmacodynamics,
acceptability and drug release data in healthy women. CONRAD A13-128 was a
randomized, placebo controlled phase I study. We screened 86 women; 51 were
randomized to TFV, TFV/LNG or placebo IVR [2:2:1] and 50 completed all visits,
using the IVR for approximately 15 days. We assessed safety by adverse events,
colposcopy, vaginal microbiota, epithelial integrity, mucosal histology and
immune cell numbers and phenotype, cervicovaginal [CV] cytokines and
antimicrobial proteins and changes in systemic laboratory measurements, and LNG
and TFV pharmacokinetics in multiple compartments. TFV pharmacodynamic activity
was measured by evaluating CV fluid [CVF] and tissue for antiviral activity using
in vitro models. LNG pharmacodynamic assessments were timed based on peak urinary
luteinizing hormone levels. All IVRs were safe with no significant colposcopic,
mucosal, immune and microbiota changes and were acceptable. Among TFV containing
IVR users, median and mean CV aspirate TFV concentrations remained above 100,000
ng/mL 4 hours post IVR insertion and mean TFV-diphosphate [DP] concentrations in
vaginal tissue remained above 1,000 fmol/mg even 3 days post IVR removal. CVF of
women using TFV-containing IVRs completely inhibited [94-100%] HIV infection in
vitro. TFV/LNG IVR users had mean serum LNG concentrations exceeding 300 pg/mL
within 1 hour, remaining high throughout IVR use. All LNG IVR users had a
cervical mucus Insler score <10 and the majority [95%] were anovulatory or had
abnormal cervical mucus sperm penetration. Estimated in vivo TFV and LNG release
rates were within expected ranges. All IVRs were safe with the active ones
delivering sustained high concentrations of TFV locally. LNG caused changes in
cervical mucus, sperm penetration, and ovulation compatible with contraceptive
efficacy. The TFV and TFV/LNG rings are ready for expanded 90 day clinical
testing. Trial registration ClinicalTrials.gov #NCT02235662.
PMID- 29953549
TI - Roux-en-Y duodenojejunostomy improves gastric emptying in experimental
obstruction of the distal duodenum.
AB - INTRODUCTION: We undertook a comparative survey of gastric emptying (GE) kinetics
after two variants of bypass surgery for upper bowel obstruction. MATERIAL &
METHODS: In 10 dogs with experimental upper bowel obstruction, five were
randomized to obtain gastrojejunal anastomosis (GA), and the other five received
Roux-en-Y duodenojejunal anastomosis (DA). Duplicate scintigraphic measurements
of GE of a solid meal were accomplished in every animal before surgery and during
the early (2-3 weeks), medium (3 months), and late (6 months) post-operative
period. The GE curves were fitted with a power-exponential function to derive the
GE half time T1/2, and the curve shape parameter S. RESULTS: Early after surgery
T1/2 slightly decreased by -18+/-21 min in the DA group and lengthened by 91+/-37
min in the GA group (p = 0.042). In both groups an increase in the S parameter
was found then. In either group T1/2 gradually declined towards the basal value
during the medium and late post-operative period. On the other hand, net
differences relative to the basal situation in the S values appeared to be
positive in the GA group (0.32+/-0.11 at 3 months; 0.64+/-0.19 at six months),
and negative in the DA group (-0.30+/-0.09 at 3 months; -0.01+/-0.20 at six
months). Hence a statistically significant contrast was found between those
differences: p = 0.0022 at 3 months, and p = 0.045 at six months after the
surgery. CONCLUSION: Roux-en-Y duodenojejunal anastomosis appears to be superior
to the classical gastrojejunal anastomosis while restoring patency of the
gastrointestinal passage in the case of upper bowel obstruction.
PMID- 29953550
TI - Variation in the calorific values of different plants organs in China.
AB - The calorific value (CAL, KJ g-1) of different plant organs are important plant
traits. Variation in CAL among different plant organs reflects the energy
utilization and distribution strategy of plant. Here, we explored how the CAL of
different plant organs varies at the species and regional level in relation to
vegetation type (3697 forests samples, 430 grasslands samples, and 146 deserts
samples). The results showed that, in the forests and grasslands, CAL
significantly differed among the different organs and functional types of plants.
The CAL of different organs in forests was ordered as: leaf (19.71 +/- 1.82 KJ g
1) > branch (19.33 +/- 1.32 KJ g-1) > trunk (19.09 +/- 1.44 KJ g-1) > root (19.02
+/- 1.11 KJ g-1). For forests, the CAL of plant organs, except for the leaves of
trees and shrubs, increased with increasing latitude (P < 0.01). In comparison,
the CAL in the roots of shrubs and herbs decreased with increasing longitude (P <
0.01). Through delineating systematic references of CAL among different plant
organs, our findings provide key parameters to improve estimates of biomass
energy at regional and global scales.
PMID- 29953552
TI - Antimicrobial resistance trends in fecal Salmonella isolates from northern
California dairy cattle admitted to a veterinary teaching hospital, 2002-2016.
AB - Nontyphoidal Salmonella infections contribute to approximately 1.2 million annual
illnesses in the United States. Historical and recent outbreaks have been
associated with dairy products, ground beef, and direct contact with cattle.
Salmonella antimicrobial resistance (AMR) is a serious concern that can reduce
successful treatment of infections, increasing recovery time, medical costs, and
mortality rates in humans and animals. This highlights the need to track AMR in
Salmonella isolated from cattle to improve treatment plans, manage trends in AMR,
and prevent future AMR development. A total of 242 Salmonella isolates were
retrieved from 9,162 cattle fecal samples submitted to the University of
California, Davis Veterinary Medical Teaching Hospital from 2002 to 2016. These
isolates were tested for antimicrobial susceptibility using a standardized broth
dilution panel. Multidrug resistance (MDR) to three or more classes of
antimicrobials was observed in 50.8% of isolates, and the most common MDR pattern
was amoxicillin-ampicillin-cefoxitin-ceftiofur-ceftriaxone-chloramphenicol
streptomycin-tetracycline (23.2%). There were significantly greater odds for
antimicrobial resistance to aminoglycosides (OR: 2.03, 95% CI: 1.1-3.7),
penicillins (OR: 1.87, 95% CI: 1.007-3.5), and tetracyclines (OR: 1.87, 95% CI:
1.017-3.4) for the 2002-2009 period when compared to the 2010-2016 period. The
most prevalent MDR serotypes were Newport (100% MDR, n = 52), Typhimurium (100%,
n = 20), and Dublin (71% MDR, n = 46). Risk factors associated with higher odds
for isolating MDR Salmonella included isolates from calves when compared to adult
cattle (OR: 22.0; 95% C.I.: 3.9-125.7), and isolates obtained from cattle suspect
of having salmonellosis versus from the infectious disease control surveillance
program (OR:13.7; 95%C.I.: 2.8-66.8). Despite a temporal trend for reduced AMR to
most antimicrobial drug classes, a lack of this observed in the 2002-2009 period
when compared to the 2010-2016 period for important drug classes such as
cephalosporins (OR: 1.6, 95% CI: 0.87-3.1), and a trend for temporal increase in
resistant to quinolones drugs (P value 0.004) highlight the relevance of AMR
surveillance in cattle with Salmonella infections with the aim of targeting
future prophylactic interventions.
PMID- 29953551
TI - Annotation, classification, genomic organization and expression of the Vitis
vinifera CYPome.
AB - Cytochromes P450 are enzymes that participate in a wide range of functions in
plants, from hormonal signaling and biosynthesis of structural polymers, to
defense or communication with other organisms. They represent one of the largest
gene/protein families in the plant kingdom. The manual annotation of cytochrome
P450 genes in the genome of Vitis vinifera PN40024 revealed 579 P450 sequences,
including 279 complete genes. Most of the P450 sequences in grapevine genome are
organized in physical clusters, resulting from tandem or segmental duplications.
Although most of these clusters are small (2 to 35, median = 3), some P450
families, such as CYP76 and CYP82, underwent multiple duplications and form large
clusters of homologous sequences. Analysis of gene expression revealed highly
specific expression patterns, which are often the same within the genes in large
physical clusters. Some of these genes are induced upon biotic stress, which
points to their role in plant defense, whereas others are specifically activated
during grape berry ripening and might be responsible for the production of berry
specific metabolites, such as aroma compounds. Our work provides an exhaustive
and robust annotation including clear identification, structural organization,
evolutionary dynamics and expression patterns for the grapevine cytochrome P450
families, paving the way to efficient functional characterization of genes
involved in grapevine defense pathways and aroma biosynthesis.
PMID- 29953553
TI - Predictors of one and two years' mortality in patients with colon cancer: A
prospective cohort study.
AB - BACKGROUND: Tools to aid in the prognosis assessment of colon cancer patients in
terms of risk of mortality are needed. Goals of this study are to develop and
validate clinical prediction rules for 1- and 2-year mortality in these patients.
METHODS: This is a prospective cohort study of patients diagnosed with colon
cancer who underwent surgery at 22 hospitals. The main outcomes were mortality at
1 and 2 years after surgery. Background, clinical parameters, and diagnostic
tests findings were evaluated as possible predictors. Multivariable multilevel
logistic regression and survival models were used in the analyses to create the
clinical prediction rules. Models developed in the derivation sample were
validated in another sample of the study. RESULTS: American Society of
Anesthesiologists Physical Status Classification System (ASA), Charlson
comorbidity index (> = 4), age (>75 years), residual tumor (R2), TNM stage IV and
log of lymph nodes ratio (> = -0.53) were predictors of 1-year mortality (C-index
(95% CI): 0.865 (0.792-0.938)). Adjuvant chemotherapy was an additional
predictor. Again ASA, Charlson Index (> = 4), age (>75 years), log of lymph nodes
ratio (> = -0.53), TNM, and residual tumor were predictors of 2-year mortality (C
index:0.821 (0.766-0.876). Chemotherapy was also an additional predictor.
CONCLUSIONS: These clinical prediction rules show very good predictive abilities
of one and two years survival and provide clinicians and patients with an easy
and quick-to-use decision tool for use in the clinical decision process while the
patient is still in the index admission.
PMID- 29953554
TI - Chemically mediated species recognition in two sympatric Grayling butterflies:
Hipparchia fagi and Hipparchia hermione (Lepidoptera: Nymphalidae, Satyrinae).
AB - Pheromones are known to play an important role in butterfly courtship and may
influence both individual reproductive success and reproductive isolation between
species. Recent studies have focused on courtship in Hipparchia butterflies
(Nymphalidae: Satyrinae) emphasizing morphological and behavioural traits, as
well as genetic differences. Behavioural observations suggested a role for
chemical cues in mate and species recognition, where the androconial scales on
the forewings of these species may be involved in chemical communication between
individuals. Cchemical-mediated signals have received relatively little attention
in this genus. Here, we report the results of a three-year investigation of the
volatile organic compounds (VOCs) released by Hipparchia fagi and H. hermione in
order to identify differences in VOCs between these species where they live in
syntopy. Our study was carried out using an array of cross-selective sensors
known as an "Electronic Nose" (EN) that operates by converting chemical patterns
into patterns of sensor signals. While the identity of volatile compounds
remained unknown, sensor signals can be compared to identify similar or
dissimilar chemical patterns. Based on the EN signals, our results showed that:
1) the two sexes have a similar VOCs pattern in H. fagi, while they significantly
diverge in H. hermione; 2) VOCs patterns were different between females of the
two species, while those of males were not.
PMID- 29953555
TI - Prevalence and determinants of diarrhea among under-five children in Ethiopia: A
systematic review and meta-analysis.
AB - BACKGROUND: Despite remarkable progress in the reduction of under-five mortality,
childhood diarrhea is still the leading cause of mortality and morbidity in this
highly susceptible and vulnerable population. In Ethiopia, study findings
regarding prevalence and determinants of diarrhea amongst under-five children
have been inconsistent. Therefore, this systematic review and meta-analysis
estimates the pooled prevalence of diarrhea and its determinants among under-five
children in Ethiopia. METHODS: International databases, including PubMed, Web of
Science, EMBASE, CINAHL, Google Scholar, Science Direct, and the Cochrane
Library, were systematically searched. All identified observational studies
reporting the prevalence and determinants of diarrhea among under-five children
in Ethiopia were included. Two authors independently extracted all necessary data
using a standardized data extraction format. STATA Version 13 statistical
software was used. The Cochrane Q test statistics and I2 test were used to assess
the heterogeneity of the studies. A random effects model was computed to estimate
the pooled prevalence of diarrhea. Moreover, the associations between determinant
factors and childhood diarrhea were examined using the random effect model.
RESULTS: After reviewing of 535 studies, 31studies fulfilled the inclusion
criteria and were included in the meta-analysis. The findings from the 31 studies
revealed that the pooled prevalence of diarrhea among under-five children in
Ethiopia was 22% (95%CI: 19, 25%). Subgroup analysis of this study revealed that
the highest prevalence was observed in Afar region (27%), followed by Somali and
Dire Dawa regions (26%), then Addis Abeba (24%). Lack of maternal education (OR:
2.5, 95% CI: 1.3, 2.1), lack of availability of latrine (OR: 2.0, 95%CI: 1.3,
3.2), urban residence (OR: 1.9, 95%CI: 1.2, 3.0), and maternal hand washing (OR:
2.2, 95%CI: 2.0, 2.6) were significantly associated with childhood diarrhea.
CONCLUSION: In this study, diarrhea among under-five children in Ethiopia was
significantly high. Lack of maternal education, lack of availability of latrine,
urban residence, and lack of maternal hand washing were significantly associated
with childhood diarrhea.
PMID- 29953556
TI - Manipulating concept spread using concept relationships.
AB - The propagation of concepts in a population of agents is a form of influence
spread, which can be modelled as a cascade from a set of initially activated
individuals. The study of such influence cascades, in particular the
identification of influential individuals, has a wide range of applications
including epidemic control, viral marketing and the study of social norms. In
real-world environments there may be many concepts spreading and interacting.
These interactions can affect the spread of a given concept, either boosting it
and allowing it to spread further, or inhibiting it and limiting its capability
to spread. Previous work does not consider how the interactions between concepts
affect concept spread. Taking concept interactions into consideration allows for
indirect concept manipulation, meaning that we can affect concepts we are not
able to directly control. In this paper, we consider the problem of indirect
concept manipulation, and propose heuristics for indirectly boosting or
inhibiting concept spread in environments where concepts interact. We define a
framework that allows for the interactions between any number of concepts to be
represented, and present a heuristic that aims to identify important influence
paths for a given target concept in order to manipulate its spread. We compare
the performance of this heuristic, called maximum probable gain, against
established heuristics for manipulating influence spread.
PMID- 29953557
TI - Dipstick proteinuria predicts all-cause mortality in general population: A study
of 17 million Korean adults.
AB - OBJECTIVE: A quantitative basis for the use of dipstick urinalysis for risk
assessment of all-cause mortality is scarce. Therefore, we investigated the
association between dipstick proteinuria and all-cause mortality in a general
population and evaluated the effect of confounders on this association. METHODS:
The study population included 17,342,956 adults who underwent health examinations
between 2005 and 2008 under the National Health Insurance System. Proteinuria was
determined using a single dipstick urinalysis, and the primary outcome of this
study was all-cause mortality. The prognostic impact of proteinuria was assessed
by constructing a multivariable Cox model. RESULTS: The mean age of the study
population (53.24% male) was 46.06 years; 724,681 deaths from all causes occurred
over a median follow-up period of 9.34 years (interquartile range 8.17-10.16),
and the maximum follow-up was 12.12 years. After full adjustment for covariates,
a higher level of dipstick proteinuria indicated a higher risk of all-cause death
[Hazard ratios (95% confidence intervals); 1.22 (1.20-1.24), 1.47 (1.45-1.49),
1.81 (1.77-1.84), 2.32 (2.24-2.41), 2.74 (2.54-2.96); trace to 4+, respectively],
and various subgroup analyses did not affect the main outcome for the total
population. >=1+ proteinuria in the group without metabolic diseases
(hypertension, diabetes, dyslipidemia, or obesity) resulted in higher hazard
ratios than those in the group with metabolic diseases and negative or trace
proteinuria. CONCLUSIONS: Our study showed a strong association between dipstick
proteinuria and all-cause mortality in this nationwide population-based cohort in
South Korea.
PMID- 29953558
TI - Retraction: The Immunoregulation Effect of Alpha 1-Antitrypsin Prolong beta-Cell
Survival after Transplantation.
PMID- 29953559
TI - Late Holocene climatic variability in Subarctic Canada: Insights from a high
resolution lake record from the central Northwest Territories.
AB - We examined late Holocene (ca. 3300 yr BP to present-day) climate variability in
the central Northwest Territories (Canadian Subarctic) using a diatom and
sedimentological record from Danny's Lake (63.48oN, 112.54oW), located 40 km
southwest of the modern-day treeline. High-resolution sampling paired with a
robust age model (25 radiocarbon dates) allowed for the examination of both lake
hydroecological conditions (30-year intervals; diatoms) and sedimentological
changes in the watershed (12-year intervals; grain size records) over the late
Holocene. Time series analysis of key lake ecological indicators (diatom species
Aulacoseira alpigena, Pseudostaurosira brevistriata and Achnanthidium
minutissimum) and sedimentological parameters, reflective of catchment processes
(coarse silt fraction), suggests significant intermittent variations in
turbidity, pH and light penetration within the lake basin. In the diatom record,
we observed discontinuous periodicities in the range of ca. 69, 88-100, 115-132,
141-188, 562, 750 and 900 years (>90% and >95% confidence intervals), whereas the
coarse silt fraction was characterized by periodicities in the >901 and <61-year
range (>95% confidence interval). Periodicities in the proxy data from the
Danny's Lake sediment core align with changes in total solar irradiance over the
past ca. 3300 yr BP and we hypothesize a link to the Suess Cycle, Gleissberg
Cycle and Pacific Decadal Oscillation via occasional inland propagation of
shifting air masses over the Pacific Ocean. This research represents an important
baseline study of the underlying causes of climate variability in the Canadian
Subarctic and provides details on the long-term climate variability that has
persisted in this region through the past three thousand years.
PMID- 29953560
TI - Correction: The modality of dialysis does not influence atheromatous vascular
disease progression or cardiovascular outcomes in dialysis patients without
previous cardiovascular disease.
AB - [This corrects the article DOI: 10.1371/journal.pone.0186921.].
PMID- 29953561
TI - Peri-implant Tissue Health and Bone Resorption in Patients with Immediately
Loaded, Implant-Supported, Full-Arch Prostheses.
AB - PURPOSE: To evaluate plaque accumulation, peri-implant soft tissue inflammation,
and bone resorption in patients with immediately loaded implants supporting fixed
full-arch prostheses. MATERIALS AND METHODS: A convenience sample of 72 patients
treated with fixed full-arch prostheses supported by four to six immediately
loaded implants was selected. Bleeding on probing (BOP), Plaque Index (PI), and
peri-implant bone loss were measured. The Sixth European Workshop on
Periodontology definitions of mucositis and peri-implantitis were used, and
collected data were analyzed using a nonparametric test (Spearman's rank
correlation). Correlation coefficients (rho) were defined as follows: < 0.2 =
very weak; 0.2 to 0.39 = weak; 0.4 to 0.59 = moderate; 0.6 to 0.79 = strong; 0.8
to 1.0 = very strong. RESULTS: A total of 331 implants were analyzed. The mean
follow-up observation time was 5.8 years (range: 1 to 14 years); mean PI and BOP
were 61.7% and 21.1%, respectively; and mean bone loss was 0.89 mm (standard
deviation [SD] 1.09). The mean probing depth was 1.8 mm (range: 0.5 to 5 mm).
Five patients presented with one implant each affected by peri-implantitis
(6.9%), and 15 patients presented with at least one implant affected by mucositis
(20.8%). No correlation was found between PI and bone resorption (P = .08). Very
weak correlations were found between BOP and bone resorption (rho = 0.18; P =
.001) and between PI and BOP (rho = 0.13, P = .019). CONCLUSION: The results
suggest that plaque accumulation is correlated with peri-implant mucositis;
however, plaque accumulation alone does not appear to be associated with bone
resorption.
PMID- 29953562
TI - Investigation of Clinical and Laboratory Wear in Locator-Supported, Implant
Retained Overdentures.
AB - PURPOSE: To investigate the mechanical properties and wear of nylon inserts and
abutments in Locator-retained, implant-supported overdentures (L-IODs). MATERIALS
AND METHODS: Clinical wear of inserts and abutments was qualitatively rated in a
group of 16 patients with L-IODs. The inserts were also subjected to microscopic
analysis, differential scanning calorimetry (DSC), and thermal gravimetric
analysis (TGA). RESULTS: Wear was identified in almost all inserts and abutments.
These results were corroborated by DSC and TGA analyses, which showed significant
mechanical deterioration of the inserts. CONCLUSION: Nylon inserts and Locator
abutments show relevant signs of deterioration in clinical use, indicating that
regular maintenance is an issue that should be addressed with the patients prior
to treatment.
PMID- 29953563
TI - An Acrylic Immobilization Bite Block for Use During Radiation Therapy:
Description of a New Technique.
AB - Utilizing intraoral bite blocks can aid in stabilizing the mandible during
radiation treatment (RT) and minimizing side effects to healthy tissues. This
report describes a technique to fabricate a customized acrylic repositioning
immobilization bite block that was integrated into the clinical workflow of
radiation appointments with no delay in starting RT and with increased patient
comfort.
PMID- 29953564
TI - Revised, Computed Tomography-Based Lekholm and Zarb Jawbone Quality
Classification.
AB - PURPOSE: To propose a revised Lekholm and Zarb classification that takes into
account all possible combinations of compact and trabecular bone and to provide
guidelines for increased reproducibility of the classification. MATERIALS AND
METHODS: Three new classes were added to the previous classification. The new
classes have been designated as subclasses of bone types 2 and 3, as follows:
Type 2b: Thick layer of compact bone surrounding a core of medium-density
trabecular bone; Type 2c: Thick layer of compact bone surrounding a core of low
density trabecular bone; and Type 3b: Thin layer of compact bone surrounding a
core of medium-density trabecular bone. Three interpretation guidelines were
recommended to increase the reproducibility of the revised classification. Three
experienced examiners were trained using the revised classification and provided
with computed tomography (CT) sectional images of edentulous jawbones for
classification. Each examiner classified the images twice with at least a 1-week
interval. The intra-observer agreement was measured. RESULTS: The kappa statistic
for the intra-observer agreement of the examiners ranged from 0.835 to 0.919 (P <
.001). CONCLUSION: The high reproducibility of the proposed revised CT-based
Lekholm and Zarb classification obtained in the current study suggests its
efficacy in distinguishing between the various combinations of compact and
trabecular bone.
PMID- 29953565
TI - Analysis of Marginal Adaptation of Porcelain Laminate Veneers Produced by
Computer-Aided Design/Computer-Assisted Manufacturing Technology: A Preliminary
In Vitro Study.
AB - PURPOSE: To analyze the marginal adaptation of computer-aided design/computer
assisted manufactured (CAD/CAM) porcelain laminate veneers. MATERIALS AND
METHODS: A total of 25 three-dimensional (3D) machine-milled laminate veneers
were divided into five groups of five each according to fabrication material (E
max; Empress; Lava Ultimate; Suprinity; and Vita Mark II) and cemented in 25
prepared acrylic central incisors. Digital microscopy images (*7.5 magnification)
were analyzed for gaps in the mesial/distal surfaces of the prepared tooth and in
the cervical, medial, and incisal thirds. RESULTS AND CONCLUSION: All CAD/CAM
laminate veneers except for Empress and Suprinity in the middle and incisal
thirds showed good results (ie, gaps < 120 MUm in the cervical, middle, and
incisal thirds).
PMID- 29953566
TI - Polylactic Acid as a Material for Three-Dimensional Printing of Provisional
Restorations.
AB - PURPOSE: To assess the marginal fit of provisional polylactic acid (PLA) crowns
obtained via three-dimensional (3D) printing using a profile projector. MATERIALS
AND METHODS: A stone cast was scanned, and 15 provisional dental crowns were
designed and printed in PLA using a 0.2-mm nozzle and 135-degree build angle. The
marginal fit was measured at six points on each crown using a profile projector.
RESULTS AND CONCLUSION: Within the limitations of this study, the marginal fit of
PLA provisional restorations was clinically acceptable, and the results were
comparable to those observed with polymethyl methacrylate provisional
restorations.
PMID- 29953567
TI - A Randomized Proof-of-Principle Bite Force Study of Two Experimental Denture
Adhesives and a Commercially Available Adhesive.
AB - PURPOSE: To assess the efficacy of two experimental denture adhesive gels
(adhesives 1 and 2) compared to a commercially available denture adhesive cream
(positive control) and no adhesive (negative control). MATERIALS AND METHODS:
This was a single-center, randomized, four-treatment, examiner-blind, crossover
study in participants with well-made and at least moderately well-fitting
maxillary complete dentures. Incisal bite force until denture dislodgment was
measured before application (baseline) and over the following 12 hours for each
of the treatments. Between-treatment differences in the area over baseline (AOB)
for the bite force at each time point were analyzed using an analysis of
covariance model. RESULTS: The efficacy and safety analyses were based on results
from 48 participants. Compared to the negative control, adhesive 1 showed a
statistically significantly higher bite force AOB over 12 hours (AOB0-12h;
primary endpoint), as well as for AOB0-6h and AOB0-9h (all P < .05), but not for
AOB0-1h or AOB0-3h. Adhesive 2 was not significantly different from the negative
control or from adhesive 1 for any measure of AOB. The positive control was
associated with a significantly higher bite force AOB than either of the
experimental adhesives for all time points (P < .05). Although the positive
control was well tolerated, both experimental adhesives were associated with a
larger number of oral adverse events. CONCLUSION: Only adhesive 1 was
significantly better than the negative control, and its performance did not match
that of the positive control. Adhesives 1 and 2 showed the largest number of oral
adverse events.
PMID- 29953568
TI - Analysis of the Marginal Fit and Dimensional Stability of Cast-to Cobalt-Chromium
Implant Cylinders Cast from Different Alloys.
AB - PURPOSE: To evaluate the influence of cobalt-chromium (Co-Cr) casting alloys'
melting temperatures on the cast-to Co-Cr implant cylinders' marginal fit.
MATERIALS AND METHODS: Co-Cr alloys with different melting ranges were cast into
20 Co-Cr cylinders: 10 in a high-melting temperature (HMT) group and 10 in a low
melting temperature (LMT) group. Ten cylinders were used as received as a control
group. Cylinders' marginal misfit and dimensional stability were evaluated using
scanning electron microscopy (*500). RESULTS AND CONCLUSION: HMT cylinders showed
significant differences in marginal misfit (2.48 +/- 1.07 MUm2) compared to LMT
(1.53 +/- 0.37 MUm2) and control (1.27 +/- 0.57 MUm2) cylinders, but there were
no differences in dimensional stability. HMT Co-Cr alloys produce implant
supported prostheses with poor marginal fit.
PMID- 29953569
TI - Influence of Mandibular Residual Ridge Morphology on Pressure Distribution During
Impression Procedures: A Model Experiment.
AB - PURPOSE: To clarify the relationship between residual ridge morphology and
pressure distribution of the alveolar bone surface during dental impression
procedures. MATERIALS AND METHODS: Seven experimental models of the mandibular
posterior residual ridge with the same ridge morphology but different mucosa (ie,
silicone material) thicknesses and bone (ie, plaster) shapes and sizes were
fabricated. The pressure on the bone surface was recorded using a pressure sensor
sheet. The data from each model were compared using the Kruskal-Wallis test, and
P < .05 was considered statistically significant. RESULTS: Even with the same
ridge morphology, the distribution of the impression pressure on the bone surface
differed according to the mucosal thickness and bone shape and size. Pressure
tended to concentrate on sharp edges and prominences of a slope and became more
widely distributed as the mucosal thickness increased. CONCLUSION: Within the
limitations of this experimental study, the morphology of the residual alveolar
ridge (bone and mucosa) appears to be a significant influencing factor for the
pressure distribution during impression procedures.
PMID- 29953570
TI - Survey of Denture Repair Cases: Denture Reinforcement Makes Patients Able to Use
Their Dentures for Longer Periods.
AB - PURPOSE: To evaluate the long-term effects of preventive measures against denture
fracture using clinical surveys of denture fracture cases from 1984 and 2009.
MATERIALS AND METHODS: This study included 128 patients who presented with a
chief complaint of denture fracture and received denture repair treatment in
2009. The following data were collected: denture repair procedure; location of
denture base fracture (with or without reinforcement); and period of denture use
from insertion to repair. Significant differences in characteristics between
patients treated in 1984 and 2009 were determined using the chi-square test (P <
.05). RESULTS: In 2009, denture fractures comprised 55.5% of all repair cases.
The most frequent location of denture fracture was around the clasp and metal in
the denture base. Approximately 45% of all dentures were reinforced. The mean
period from denture insertion to repair was 37 months. The number of denture
fractures significantly decreased between 1984 and 2009 (P < .05), and the number
of dentures with reinforcement significantly increased (P < .05). The mean period
from denture insertion to repair also increased. CONCLUSION: These findings
suggest that denture reinforcement as a preventive measure is effective against
denture fracture, allowing patients to use their dentures more effectively.
PMID- 29953571
TI - Revisiting the anaesthesiologist's role during organ procurement.
AB - As organ transplantation science continues to mature, both physicians and the
public face challenges defining death and, subsequently, caring for an individual
when they are deemed eligible for organ procurement. This paper revisits the
anaesthesiologist's role with respect to the provision of analgesic medication at
the time of organ procurement. It provides a historical overview of the ethics of
organ procurement, explaining how the definition of brain death and the ethical
principle of the 'dead donor rule' have shaped the practice of organ procurement.
It concludes by suggesting that a re-framing of the ethics of organ procurement
may be necessary in order for anaesthesiologists to meet their ethical obligation
of preventing harm to organ donors while maintaining public trust in the medical
profession.
PMID- 29953572
TI - The influence of gradually increasing the concentration of desflurane on cerebral
perfusion pressure in rabbit.
AB - BACKGROUND: In nearly all cases of general anaesthesia with a volatile agent, the
anaesthetic concentration has to be increased. Since the anaesthetic affects both
the factors determining intracranial homeostasis and the systemic circulation, it
is crucial that cerebral perfusion pressure (CPP) is protected. The aim of the
present study was to assess the influence of gradually increased concentrations
of desflurane on the cerebral and systemic circulations based on CPP, mean
arterial pressure (MAP), intracranial pressure (ICP) and their correlations.
METHODS: The study was carried out on 25 rabbits of the same gender (male)
randomly assigned to two groups: control (n = 10) and group I (n = 15). Over
three 15-minute periods, the animals were exposed to increase concentrations of
desflurane so as to achieve 1/3, 2/3 and 1 MAC Minimal Alveolar Concentration (3,
6, 9 vol%) of the effective end-tidal concentration of desflurane (Et) at the end
of each period, respectively. RESULTS: Intragroup analysis of CPP changes
demonstrated decreases in its successive values from minute 18, compared with
baseline values. The mean values of ICP did not differ throughout the experiment.
From minute 19 on, all successive values of MAP decreased compared with baseline
values. A weak correlation (r = -0.2179) was found between ICP and CPP and a
strong correlation between MAP and CPP (r = 0.98829). Moreover, there was a
strong correlation between Etdesflurane vs. CPP (r = -0.8769) and MAP (r =
0.8224) and a weak correlation versus ICP (r = 0.15755). CONCLUSIONS: A decrease
in CPP induced by desflurane was associated with a decrease in MAP but not an
increase in ICP. The depressive effect of desflurane on the cerebral and systemic
circulations is a consequence of its effector site concentration.
PMID- 29953573
TI - Ultrasound-based assessment of hyomental distances in neutral, ramped, and
maximum hyperextended positions, and derived ratios, for the prediction of
difficult airway in the obese population: a pilot diagnostic accuracy study.
AB - BACKGROUND: Ultrasonography-assessed hyomental distance (HMD) ratio has been
found to discriminate between obese patients with Cormack-Lehane grades 1 or 2
vs. those with grades 3 or 4. The aim of our study is to evaluate the performance
of the HMD evaluated ultrasonographically in neutral, ramped, and maximum
hyperextended positions, as well as for the ratios obtained by dividing the HMD
in the ramped position to that in the neutral position (HMDR1) and by dividing
the HMD in maximum hyperextension to that in the neutral position (HMDR2), in
order to predict the occurrence of Cormack-Lehane grades 3 or 4 during direct
laryngoscopy. METHODS: Ultrasound measurements were performed preoperatively in
25 patients with morbid obesity, measuring the HMD in the neutral, ramped, and
maximum hyperextended positions. Pre-epyglotic soft tissue thickness, Mallampati
and upper lip bite test scores were recorded. Cormack-Lehane grading was
considered as an outcome variable in the Receiver Operating Characteristics curve
analysis. RESULTS: HMD in the neutral, ramped and maximum hyperextended positions
presented similar sensitivities, 100% [39.8-100.0]. For HMD, specificity was
42.86% [21.8-66.0] in the neutral position, 61.9% [38.4-81.9] in the ramped
postion, and 71.4% [47.8-88.7] in the maximum hyperextended position. For HMDR1,
the cut-off value was 1.12. This threshold provides 75% [19.4-99.4] sensitivity
and 76.2% [52.8-91.8] specificity. For HMDR2, a cut-off value of 1.23 provides
100% [39.8-100.0] sensitivity and 90.5% [69.6-98.8] specificity. CONCLUSION:
HMDR2 seems to have superior diagnostic accuracy in predicting difficult
laryngoscopy in the obese population compared to HMDR1, as well as compared to
the HMD in the neutral, ramped, and maximum hyperextended positions.
PMID- 29953574
TI - C-reactive protein level in plasma and drainage blood depends on the method of
anaesthesia and post-operative analgesia after hip surgery.
AB - BACKGROUND: Serum C-reactive protein (CRP) detects the inflammatory response to
surgical trauma in hip surgery. It corresponds to the type of surgery, with a
higher level of CRP being found in surgery techniques with greater tissue damage.
The aim of our study was to analyze the CRP level in serum and drainage blood
after hip surgery in patients with coxarthrosis depending on the method of
anaesthesia and post-operative analgesia. METHODS: 65 patients, 58 +/- 12 years
old, were included in the study. All patients underwent hip replacement surgery
due to coxarthrosis. Serum CRP was measured before surgery and on the 1st, 3rd
and 7th postoperative days. The CRP level in drainage blood was detected on the
1st, 2nd and 3rd postoperative days. Patients were divided into six groups
according to the techniques of intraoperative anaesthesia and postoperative
analgesia. RESULTS: Before surgery, plasma CRP did not differ significantly among
the groups. The smallest increase in plasma CRP was found in patients operated on
under regional anaesthesia compared with those operated on under general
anaesthesia. Postoperatively, the plasma CRP level was higher in patients treated
with the systemic administration of opioids+NSAID, than in patients treated with
regional analgesia. A significant increase in CRP levels in drainage blood for
three days postoperatively was seen in all groups. In patients operated on under
general anaesthesia and receiving systemic opioids+NSAID postoperatively, CRP in
drainage blood was higher in comparison with those operated on under regional
anaesthesia and treated with regional methods of postoperative analgesia.
CONCLUSION: C-reactive protein levels in plasma and drainage blood depends on the
method of anaesthesia and postoperative analgesia after hip surgery. Regional
anaesthesia/analgesia methods limit one's inflammatory response to surgical
trauma detected by CRP.
PMID- 29953575
TI - Hypertonic saline-hydroxyethyl starch solution attenuates fluid accumulation in
cardiac surgery patients: a randomized controlled double-blind trial.
AB - BACKGROUND: Significant fluid retention is common after cardiac surgery with the
use of cardiopulmonary bypass (CPB). The aim of the study was to evaluate the
effects of hypertonic saline-hydroxyethyl starch (HS-HES) solution on fluid
accumulation in patients undergoing coronary artery bypass grafting surgery
(CABG). METHODS: Fifty adult male patients undergoing coronary bypass surgery
were enrolled in this interventional, randomized, double-blinded study to compare
HS-HES with saline solution. The study fluid (250 mL) was given into the venous
reservoir of the CPB circuit at the time of aortic declamping. RESULTS: Body mass
change from the baseline to the first postoperative morning was significantly
less in the HS-HES group compared with the control group (3.3 +/- 1.5 kg vs. 4.4
+/- 1.5 kg, P = 0.022). In the extracellular water (ECW) or ECW-balance, there
were no significant differences between the groups. The need for fluids and
diuretic medication did not differ between the groups during the perioperative
period. CONCLUSIONS: Our study shows that 250 mL of HS-HES solution can reduce
perioperative fluid accumulation to some degree in patients undergoing CABG
surgery with CPB.
PMID- 29953576
TI - Emergence from anesthesia: a winding way back.
AB - none.
PMID- 29953577
TI - Acquired haemophilia A imitating uterine tumour in a patient with de novo
diagnosis of hepatitis C.
AB - AHA is an extremely rare disorder, with annual incidence of 1.5 cases per million
population. This clinical entity is caused by autoantibodies directed against
coagulation factor VIII, what leads to decreased serum activity of thereof, and
is characterized by spontaneous or induced by trauma, or invasive procedure
bleeding. Approximately 50% of cases are idiopathic in origin, affecting both
sexes, with median age at diagnosis of 74 years. We present a case report of a
patient diagnosed with acquired haemophilia A (AHA) in the perioperative period.
PMID- 29953578
TI - Assessment of Consistency of Drug Interaction Information in Drug Labels Among
the United States, the United Kingdom, China, Japan, and Korea.
AB - Information gap in drug labeling among countries create challenges in therapeutic
use of drugs. We aimed to evaluate the consistency of drug interaction
information in drug labels among five countries. The study drugs were chosen from
the commonly approved drug list in the US, UK, China, Japan, and Korea. The
degree of agreement of drug interaction data was evaluated by kappa coefficient.
Thirty-eight drugs were evaluated, and moderate degree of agreement was observed
among all countries' labeling (kappa = 0.43, 95% confidence interval (CI) = 0.41
0.46). The degree of agreement was the highest for the UK and Korea (kappa =
0.71, 95% CI = 0.67-0.75) and the lowest for the UK and Japan (kappa = 0.02, 95%
CI = 0.00-0.04). Information regarding drug interactions listed in the studied
drug labels was not in high agreement. International standardization of drug
labeling is required to ensure safe drug therapy.
PMID- 29953579
TI - Epilepsy in Asia: Disease burden, management barriers, and challenges.
AB - This article reviews the burden of epilepsy in Asia, the challenges faced by
people with epilepsy, and the management of epilepsy. Comparison is made with
other parts of the world. For this narrative review, data were collected using
specified search criteria. Articles investigating the epidemiology of epilepsy,
diagnosis, comorbidities and associated mortality, stigmatization, and treatment
were included. Epilepsy is a global health care issue affecting up to 70 million
people worldwide. Nearly 80% of people with epilepsy live in low- and middle
income countries with limited resources. People with epilepsy are prone to
physical and psychological comorbidities, including anxiety and depression, which
can negatively impact their quality of life. Furthermore, people with epilepsy
are at higher risk of premature death than people without epilepsy.
Discrimination or stigmatization of people with epilepsy is common in Asia and
can affect their education, work, and marriage opportunities. Access to epilepsy
treatment varies throughout Asia. Although highly advanced treatment is available
in some countries, up to 90% of people with epilepsy are not adequately treated
or are not treated with conventional antiepileptic therapy in resource-limited
countries. People in remote areas often do not receive any epilepsy care. First
generation antiepileptic drugs (AEDs) are available, but usually only in urban
areas, and second-generation AEDs are not available in all countries. Newer AEDs
tend to have more favorable safety profiles than first-generation AEDs and
provide options to tailor therapy for individual patients, especially those with
comorbidities. Active epilepsy surgery centers are present in some countries,
although epilepsy surgery is often underutilized given the number of patients who
could benefit. Further epidemiologic research is needed to provide accurate
epilepsy data across the Asian region. Coordinated action is warranted to improve
access to treatment and care.
PMID- 29953581
TI - Using Genetic Variants in the Targets of Lipid Lowering Therapies to Inform Drug
Discovery and Development: Current and Future Treatment Options.
AB - Mendelian randomization studies and "human knock-out" studies of rare loss-of
function coding variants suggest that plasma levels of low-density lipoprotein
cholesterol LDL-C, triglycerides (TGs), and lipoprotein(a) (Lp(a)) are causally
associated with the risk of cardiovascular disease, and, therefore, therapies
directed against these targets should reduce the risk of cardiovascular events.
However, several therapies directed against these targets have failed to reduce
the risk of cardiovascular events in large-scale randomized trials, thus
suggesting that causality is not sufficient evidence to establish genetic target
validation. Instead, the critical question that needs to be answered to improve
drug discovery and development is how much a causal biomarker needs to be changed
to produce a clinically meaningful benefit in a short-term trial. This review
describes how to use naturally randomized genetic evidence to accurately
anticipate the results of randomized trials evaluating current and future lipid
lowering therapies, inform the design of randomized trials, and transform the
drug discovery and development process.
PMID- 29953580
TI - Identification of novel macropinocytosis inhibitors using a rational screen of
Food and Drug Administration-approved drugs.
AB - BACKGROUND AND PURPOSE: Macropinocytosis is involved in many pathologies,
including cardiovascular disorders, cancer, allergic diseases, viral and
bacterial infections. Unfortunately, the currently available pharmacological
inhibitors of macropinocytosis interrupt other endocytic processes and have non
specific endocytosis-independent effects. Here we have sought to identify new,
clinically relevant inhibitors of macropinocytosis, using an FDA-approved drug
library. EXPERIMENTAL APPROACH: In the present study, 640 FDA-approved compounds
were tested for their ability to inhibit macropinocytosis. A series of secondary
assays were performed to confirm inhibitory activity, determine IC50 values and
investigate cell toxicity. The ability of identified hits to inhibit phagocytosis
and clathrin-mediated and caveolin-mediated endocytosis was also investigated.
Scanning electron microscopy and molecular biology techniques were utilized to
examine the mechanisms by which selected compounds inhibit macropinocytosis. KEY
RESULTS: The primary screen identified 14 compounds that at ~10 MUM concentration
inhibit >95% of macropinocytotic solute internalization. Three compounds -
imipramine, phenoxybenzamine and vinblastine - potently inhibited (IC50 <= 131
nM) macropinocytosis without exerting cytotoxic effects or inhibiting other
endocytic pathways. Scanning electron microscopy imaging indicated that
imipramine inhibits membrane ruffle formation, a critical early step leading to
initiation of macropinocytosis. Finally, imipramine has been shown to inhibit
macropinocytosis in several cell types, including cancer cells, dendritic cells
and macrophages. CONCLUSIONS AND IMPLICATIONS: Our results identify imipramine as
a new pharmacological tool to study macropinocytosis in cellular and biological
systems. This study also suggests that imipramine could be a good candidate for
repurposing as a therapeutic agent in pathological processes involving
macropinocytosis.
PMID- 29953582
TI - Deep-learning-based, computer-aided classifier developed with a small dataset of
clinical images surpasses board-certified dermatologists in skin tumour
diagnosis.
AB - BACKGROUND: Application of deep-learning technology to skin cancer classification
can potentially improve the sensitivity and specificity of skin cancer screening,
but the number of training images required for such a system is thought to be
extremely large. OBJECTIVES: To determine whether deep-learning technology could
be used to develop an efficient skin cancer classification system with a
relatively small dataset of clinical images. METHODS: A deep convolutional neural
network (DCNN) was trained using a dataset of 4867 clinical images obtained from
1842 patients diagnosed with skin tumours at the University of Tsukuba Hospital
from 2003 to 2016. The images consisted of 14 diagnoses, including both malignant
and benign conditions. Its performance was tested against 13 board-certified
dermatologists and nine dermatology trainees. RESULTS: The overall classification
accuracy of the trained DCNN was 76.5%. The DCNN achieved 96.3% sensitivity
(correctly classified malignant as malignant) and 89.5% specificity (correctly
classified benign as benign). Although the accuracy of malignant or benign
classification by the board-certified dermatologists was statistically higher
than that of the dermatology trainees (85.3% +/- 3.7% and 74.4% +/- 6.8%, P <
0.01), the DCNN achieved even greater accuracy, as high as 92.4% +/- 2.1% (P <
0.001). CONCLUSIONS: We have developed an efficient skin tumour classifier using
a DCNN trained on a relatively small dataset. The DCNN classified images of skin
tumours more accurately than board-certified dermatologists. Collectively, the
current system may have capabilities for screening purposes in general medical
practice, particularly because it requires only a single clinical image for
classification.
PMID- 29953584
TI - Perampanel: Does it have broad-spectrum potential?
AB - This article reviews the profile of perampanel, a novel noncompetitive alpha
amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist, and
its role as a potential broad-spectrum antiepileptic drug in the treatment of
epilepsy. For this narrative review, data were collected using specified search
criteria. Articles reporting the evidence for perampanel's efficacy from
preclinical models, phase 3 clinical studies, observational studies, and
descriptive evidence were included. AMPA receptors play a key role in mediating
the action of glutamate at the excitatory synapse. Preclinical research showed
the AMPA receptor blockade to constitute a promising target for antiepileptic
drug therapy. In animal models, perampanel proved to be protective against
seizures and reduce seizure severity and duration. Four phase-3 randomized
controlled trials (3 in patients with focal seizures and one in primary
generalized tonic-clonic seizures in idiopathic generalized epilepsy) have been
completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg)
significantly reduced seizure frequency per 28 days (23.3%-28.8% vs 12.8%; P <
.01) and responder rates (>=50% reduction in seizures) (28.5%-35.3% vs 19.3%; P <
.05) compared with placebo. In primary generalized tonic-clonic seizures,
perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (
76.5% vs -38.4%; P < .0001) and responder rate (64.2% vs 39.5%; P = .0019) than
placebo. The efficacy, safety, and tolerability of perampanel have been
reproduced in real-world clinical practice, and the agent has been shown to be
effective in other epilepsy syndromes. Perampanel is a potentially broad-spectrum
antiepileptic drug with a novel mechanism of action that may be a useful addition
for patients with epilepsy with various seizure types. The availability of novel
antiepileptic drugs for epilepsy treatment enables more individualized treatment
for these patients.
PMID- 29953583
TI - LPL protein in Chronic Lymphocytic Leukaemia have different origins in Mutated
and Unmutated patients. Advances for a new prognostic marker in CLL.
AB - Lipoprotein lipase (LPL) mRNA expression in chronic lymphocytic leukaemia (CLL)
is associated with an unmutated immunoglobulin profile and poor clinical outcome.
We evaluated the subcellular localization of LPL protein in CLL cells that did or
did not express LPL mRNA. Our results show that LPL protein is differently
located in CLL cells depending on whether it is incorporated from the
extracellular medium in mutated CLL or generated de novo by leukaemic cells of
unmutated patients. The specific quantification of endogenous LPL protein
correlates with mRNA expression levels and mutational IGHV status, suggesting LPL
protein as a possible reliable prognostic marker in CLL.
PMID- 29953585
TI - ATLANTIC AMPHIBIANS: a data set of amphibian communities from the Atlantic
Forests of South America.
AB - Amphibians are among the most threatened vertebrates in the world and this is
also true for those inhabiting the Atlantic Forest hotspot, living in ecosystems
that are highly degraded and threatened by anthropogenic activities. We present a
data set containing information about amphibian communities sampled throughout
the Atlantic Forest Biome in South America. The data were extracted from 389
bibliographic references (articles, books, theses, and dissertations)
representing inventories of amphibian communities from 1940 to 2017. The data set
includes 17,619 records of 528 species with taxonomic certainty, from 1,163 study
sites. Of all the records, 14,450 (82%) were classified using the criterion of
endemism; of those, 7,787 (44%) were considered endemic and 6,663 (38%) were not.
Historically, multiple sampling methods were used to survey amphibians, the most
representative methods being active surveys (82.1%), surveys at breeding sites
(20%), pitfall traps (15.3%), and occasional encounters (14.5%). Species richness
averaged 15.2 +/- 11.3 (mean +/- SD), ranging from 1 to 80 species per site. We
found a low dominance in the communities, with 10 species occurring in about 26%
of communities: Physalaemus cuvieri (4.1%), Dendropsophus minutus (3.8%), Boana
faber (3.1%), Scinax fuscovarius (2.8%), Leptodactylus latrans (2.7%),
Leptodactylus fuscus (2.6%), Boana albopunctata (2.3%), Dendropsophus nanus
(1.6%), Rhinella ornata (1.6%), and Leptodactylus mystacinus (1.6%). This data
set represents a major effort to compile inventories of amphibian communities for
the Neotropical region, filling a large gap in the data on the Atlantic Forest
hotspot. We hope this data set can be used as a credible tool in the proposal of
new studies on amphibian sampling and even in the development of conservation
planning for these taxa. This information also has great relevance for
macroecological studies, being foundational for both conservation and restoration
strategies in this biodiversity hotspot. No copyright or proprietary restrictions
are associated with the use of this data set. Please cite this data paper when
the data are used in publications or teaching events.
PMID- 29953586
TI - Quantitative positron emission tomography-guided magnetic resonance imaging
postprocessing in magnetic resonance imaging-negative epilepsies.
AB - OBJECTIVE: Detection of focal cortical dysplasia (FCD) is of paramount importance
in epilepsy presurgical evaluation. Our study aims at utilizing quantitative
positron emission tomography (QPET) analysis to complement magnetic resonance
imaging (MRI) postprocessing by a morphometric analysis program (MAP) to
facilitate automated identification of subtle FCD. METHODS: We retrospectively
included a consecutive cohort of surgical patients who had a negative
preoperative MRI by radiology report. MAP was performed on T1-weighted volumetric
sequence and QPET was performed on PET/computed tomographic data, both with
comparison to scanner-specific normal databases. Concordance between MAP and QPET
was assessed at a lobar level, and the significance of concordant QPET-MAP+
abnormalities was confirmed by postresective seizure outcome and histopathology.
QPET thresholds of standard deviations (SDs) of -1, -2, -3, and -4 were evaluated
to identify the optimal threshold for QPET-MAP analysis. RESULTS: A total of 104
patients were included. When QPET thresholds of SD = -1, -2, and -3 were used,
complete resection of the QPET-MAP+ region was significantly associated with
seizure-free outcome when compared with the partial resection group (P = 0.023, P
< 0.001, P = 0.006) or the no resection group (P = 0.002, P < 0.001, P = 0.001).
The SD threshold of -2 showed the best combination of positive rate (55%),
sensitivity (0.68), specificity (0.88), positive predictive value (0.88), and
negative predictive value (0.69). Surgical pathology of the resected QPET-MAP+
areas revealed mainly FCD type I. Multiple QPET-MAP+ regions were present in 12%
of the patients at SD = -2. SIGNIFICANCE: Our study demonstrates a practical and
effective approach to combine quantitative analyses of functional (QPET) and
structural (MAP) imaging data to improve identification of subtle epileptic
abnormalities. This approach can be readily adopted by epilepsy centers to
improve postresective seizure outcomes for patients without apparent lesions on
MRI.
PMID- 29953587
TI - Effects of eslicarbazepine on slow inactivation processes of sodium channels in
dentate gyrus granule cells.
AB - OBJECTIVE: Pharmacoresistance is a problem affecting ~30% of chronic epilepsy
patients. An understanding of the mechanisms of pharmacoresistance requires a
precise understanding of how antiepileptic drugs interact with their targets in
control and epileptic tissue. Although the effects of (S)-licarbazepine (S-Lic)
on sodium channel fast inactivation are well understood and have revealed
maintained activity in epileptic tissue, it is not known how slow inactivation
processes are affected by S-Lic in epilepsy. METHODS: We have used voltage clamp
recordings in isolated dentate granule cells (DGCs) and cortical pyramidal
neurons of control versus chronically epileptic rats (pilocarpine model of
epilepsy) and in DGCs isolated from hippocampal specimens from temporal lobe
epilepsy patients to examine S-Lic effects on sodium channel slow inactivation.
RESULTS: S-Lic effects on entry into and recovery from slow inactivation were
negligible, even at high concentrations of S-Lic (300 MUmol/L). Much more
pronounced S-Lic effects were observed on the voltage dependence of slow
inactivation, with significant effects at 100 MUmol/L S-Lic in DGCs from control
and epileptic rats or temporal lobe epilepsy patients. For none of these effects
of S-Lic could we observe significant differences either between sham-control and
epileptic rats, or between human DGCs and the two animal groups. S-Lic was
similarly effective in cortical pyramidal neurons from sham-control and epileptic
rats. Finally, we show in expression systems that S-Lic effects on slow
inactivation voltage dependence are only observed in Nav 1.2 and Nav 1.6
subunits, but not in Nav 1.1 and Nav 1.3 subunits. SIGNIFICANCE: From these data,
we conclude that a major mechanism of action of S-Lic is an effect on slow
inactivation, primarily through effects on slow inactivation voltage dependence
of Nav 1.2 and Nav 1.6 channels. Second, we demonstrate that this main effect of
S-Lic is maintained in both experimental and human epilepsy and applies to
principal neurons of different brain areas.
PMID- 29953588
TI - NLRP3 inflammasome mediates chronic intermittent hypoxia-induced renal injury
implication of the microRNA-155/FOXO3a signaling pathway.
AB - Chronic intermittent hypoxia (CIH), as the foremost pathophysiological change of
obstructive sleep apnea (OSA), contributes to continued deterioration in renal
function. Nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome
is a multiprotein complex that triggers innate immune responses to infection and
cell stress through activation of caspase-1 and maturation of inflammatory pro
interleukin-1beta cytokine. Emerging evidence indicates that inhibition of the
NLRP3 inflammasome ameliorates renal injury. Nevertheless, it is uncertain
whether NLRP3 inflammasome participates in CIH-induced renal injury. The
molecular mechanisms modulating NLRP3 inflammasome activation remain to be
elucidated. Compared with wild-type mice, NLRP3 knockout mice dramatically
protected them from kidney injury, as indicated by the restoration of creatinine
levels, lessened histopathological alterations, and the suppression of
macrophages infiltration stained with F4/80. NLRP3 deficiency notably reversed
CIH-induced oxidative stress (malondialdehyde and superoxide dismutase),
concomitantly with the abrogated apoptosis-related proteins and proinflammatory
signaling pathway. Consistently, NLRP3-deficient tubular cells remarkably
inhibited reactive oxygen species generation and NLRP3 inflammasome activation.
Furthermore, our study revealed that microRNA-155 (miR-155) was augmented in the
renal tissue and HK-2 cells exposed to CIH. In addition, we investigated the role
of miR-155 in the regulation of NLRP3 inflammasome. Inhibition of miR-155
suppressed the CIH-induced NLRP3 inflammasome activation in renal tubular cells,
whereas overexpression of miR-155 promoted oxidation and enhanced NLRP3 pathway.
Collectively, we demonstrated that miR-155 might be a positive-regulator of NLRP3
pathway by inhibiting the targeted FOXO3a gene. These results established a link
between the miR-155/FOXO3a pathway and the NLRP3 inflammasome, suggesting
pharmacological blockage of NLRP3 as a potential therapeutic strategy for OSA
associated chronic kidney disease.
PMID- 29953589
TI - Aerobic exercise, but not metformin, prevents reduction of muscular performance
by AMPk activation in mice on doxorubicin chemotherapy.
AB - Doxorubicin (DOX) is a chemotherapy agent widely used in clinical practice, and
it is very efficient in tumor suppression, but the use of DOX is limited by a
strong association with the development of severe muscle atrophy and
cardiotoxicity effects. Reversion or neutralization of the muscular atrophy can
lead to a better prognosis. Recent studies have proposed that the negative effect
of DOX on skeletal muscle is linked to its inhibition of AMP-activated protein
kinase (AMPk), a key mediator of cellular metabolism. On the basis of this, our
goal was to evaluate if aerobic exercise or metformin treatment, activators of
AMPk, would be able to attenuate the deleterious effects on skeletal muscle
induced by the DOX treatment. C57BL6 mice received either saline (control) or DOX
(2.5 mg/kg body weight) intraperitoneally, twice a week. The animals on DOX were
further divided into groups that received adjuvant treatment in the form of
moderate aerobic physical exercise (DOX+T) or metformin gavage (300 mg/body
weight/day). Body weight, metabolism, distance run, muscle fiber cross-sectional
area (CSA), and protein synthesis and degradation were assessed. We demonstrated
that aerobic training, but not metformin, associated with DOX increased the
maximal aerobic capacity without changing muscle mass or fiber CSA, rescuing the
muscle fatigue observed with DOX treatment alone. This improvement was associated
with AMPk activation, thus surpassing the negative effects of DOX on muscle
performance and bioenergetics. In conclusion, aerobic exercise increases AMPk
activation and improved the skeletal muscle function, reducing the side effects
of DOX.
PMID- 29953590
TI - Bone and bone marrow disruption by endocrine-active substances.
AB - Bone is a multifaceted dynamic tissue, involved in mobility, mineral metabolism,
and mesenchymal or stromal and hematopoietic progenitor or stem cells breading.
Recently, an endocrine role has been attributed to bone due to its ability to
produce at least two hormones (osteocalcin and fibroblast growth factor 23) and
to participate directly or indirectly in leptin, insulin, estrogens, and
serotonin signaling; regulation; and action. Also, bearing in mind the enormous
amounts of substances secreted by the different bone marrow cell types, it
becomes understandable the contribution of bone tissue to systemic homeostasis.
Besides, bone is a well-known estrogen-responsive tissue, reacting to
environmental influences. Thus, it has been coined as a critical target of
environmental xenoestrogens, known as endocrine-disrupting chemicals (EDCs). The
exposure to EDCs results to disruption or imbalance of the systemic hormonal
regulation of the skeleton including bone modeling and remodeling, local
hormones, and cytokine or chemokine release. The present report highlights the
harmful EDCs effects on bone tissue and provides up-to-date information of
xenoestrogen action on proliferation, maturation, and homing of bone marrow
inhabitants.
PMID- 29953594
TI - AORN Position Statement on Criminalization of Human Errors in the Perioperative
Setting.
PMID- 29953591
TI - RUMI is a novel negative prognostic marker and therapeutic target in non-small
cell lung cancer.
AB - Recent comprehensive next-generation genome and transcriptome analyses in lung
cancer patients, several clinical observations, and compelling evidence from
mouse models of lung cancer have uncovered a critical role for Notch signaling in
the initiation and progression of non-small-cell lung cancer (NSCLC). Notably,
Rumi is a "protein O-glucosyltransferase" that regulates Notch signaling through
O-glucosylation of Notch receptors, and is the only enzymatic regulator whose
activity is required for both ligand-dependent and ligand-independent activation
of Notch. We have conducted a detailed study on RUMI's involvement in NSCLC
development and progression, and have further explored the therapeutic potential
of its targeting in NSCLC. We have determined that Rumi is highly expressed in
the alveolar and bronchiolar epithelia, including club cells and alveolar type II
cells. Remarkably, RUMI maps to the region of chromosome 3q that corresponds to
the major signature of neoplastic transformation in NSCLC, and is markedly
amplified and overexpressed in NSCLC tumors. Notably, RUMI expression levels are
predictive of poor prognosis and survival in NSCLC patients. Our data indicates
that RUMI modulates Notch activity in NSCLC cells, and that its silencing
dramatically decreases cell proliferation, migration, and survival. RUMI
downregulation causes severe cell cycle S-phase arrest, increases genome
instability, and induces late apoptotic-nonapoptotic cell death. Our studies
demonstrate that RUMI is a novel negative prognostic factor with significant
therapeutic potential in NSCLC, which embodies particular relevance especially
when considering that, while current Notch inhibitory strategies target only
ligand-dependent Notch activation, a large number of NSCLCs are driven by ligand
independent Notch activity.
PMID- 29953596
TI - Clinical Issues-July 2018: 1.5 www.aornjournal.org/content/cme.
PMID- 29953592
TI - Only a subpopulation of mouse sperm displays a rapid increase in intracellular
calcium during capacitation.
AB - Mammalian sperm must undergo a functionally defined process called capacitation
to be able to fertilize oocytes. They become capacitated in vivo by interacting
with the female reproductive tract or in vitro in a defined capacitation medium
that contains bovine serum albumin, calcium (Ca2+ ), and bicarbonate (HCO3 - ).
In this work, sperm were double stained with propidium iodide and the Ca2+ dye
Fluo-4 AM and analyzed by flow cytometry to determine changes in intracellular
Ca2+ concentration ([Ca2+ ]i ) in individual live sperm. An increase in [Ca2+ ]i
was observed in a subpopulation of capacitated live sperm when compared with
noncapacitated ones. Sperm exposed to the capacitating medium displayed a rapid
increase in [Ca2+ ]i within 1 min of incubation, which remained sustained for 90
min. These rise in [Ca2+ ]i after 90 min of incubation in the capacitating medium
was evidenced by an increase in the normalized median fluorescence intensity.
This increase was dependent on the presence of extracellular Ca2+ and, at least
in part, reflected the contribution of a new subpopulation of sperm with higher
[Ca2+ ]i . In addition, it was determined that the capacitation-associated [Ca2+
]i increase was dependent of CatSper channels, as sperm derived from CatSper
knockout (CatSper KO) or incubated in the presence of CatSper inhibitors failed
to increase [Ca2+ ]i . Surprisingly, a minimum increase in [Ca2+ ]i was also
observed in CatSper KO sperm suggesting the existence of other Ca2+ transport
systems. Altogether, these results indicate that a subpopulation of sperm
increases [Ca2+ ]i very rapidly during capacitation mainly due to a CatSper
mediated influx of extracellular Ca2+ .
PMID- 29953595
TI - Parental Perception of the Perioperative Experience for Children With Autism.
AB - Children with autism spectrum disorders (ASDs) face unique challenges when
preparing for and undergoing surgery in the perioperative setting. Our goal was
to describe this experience via the qualitative evaluation of interviews with
parents whose children with ASD had recently undergone surgery in a tertiary
medical center. Twelve parents or guardians participated in these interviews. Two
independent researchers recorded interviews and analyzed transcripts. The
researchers analyzed the interview transcripts using qualitative software to
determine the categories of frequent answers to interview questions. Important
categories that emerged included behavioral triggers (ie, response to sounds,
expression of anxiety and pain), objects used for comfort, communication issues,
important people, and advice. We found that children with ASD have specific and
unique needs for reassurance and comfort during a perioperative visit. We created
a tool, included in this article, to provide a patient-centered framework for
interactions with children with ASD in the perioperative environment.
PMID- 29953597
TI - Positioning Patients Undergoing Orthopedic Procedures.
AB - Positioning patients for orthopedic procedures can be a daunting experience for
nurses because of the wide variety of orthopedic procedures and available
positioners. Understanding what to use for a particular procedure can help
perioperative nurses feel more confident and allow them to provide the safest
patient care possible. This knowledge also helps avoid workflow delays because of
missing or incorrect equipment. Educators or senior staff nurses can provide
access to information and education that will help ensure that nurses provide
efficient, safe care for patients undergoing orthopedic procedures. Training
should begin in the employee orientation phase and be provided when new additions
or modifications to positioning policies occur. The educator should validate
staff member competency on a regular basis to help ensure the correct equipment
is used and to disseminate knowledge regarding any changes or upgrades to
positioners.
PMID- 29953598
TI - 2018 Conference Poster Collection.
PMID- 29953599
TI - Mock ORs help engage perioperative personnel in design decisions.
PMID- 29953601
TI - Did You Know?
PMID- 29953600
TI - Back to Basics: Protection From Surgical Smoke: 1.2
www.aornjournal.org/content/cme.
AB - Surgical smoke is formed when energy-generating devices (ie, electrosurgery
units, lasers, powered instruments) raise the intracellular temperature of tissue
to at least 100o C (212o F), causing tissue vaporization in the form of surgical
smoke. Surgical smoke contains components that are known health hazards, such as
benzene, toluene, hydrogen cyanide, formaldehyde, volatile organic compounds,
viruses, and bacteria. There have been case reports of human disease tied to the
inhalation of surgical smoke; therefore, it is important for perioperative team
members to minimize their exposure and patient exposure. In spite of the health
risks, many perioperative departments do not consistently and effectively
evacuate surgical smoke. This Back to Basics article provides basic steps that
perioperative team members can take to protect themselves and their patients from
the harm caused by surgical smoke exposure.
PMID- 29953602
TI - Developing Critical Thinking in Perioperative Staff Members.
PMID- 29953603
TI - Unexpected Drawbacks of Electronic Order Sets.
PMID- 29953605
TI - Advances in Orthopedic Surgery.
PMID- 29953604
TI - Establishing a Successful Outpatient Joint Arthroplasty Program.
AB - Many surgical procedures are performed in outpatient settings, and outpatient
joint replacements are one of the emerging trends in orthopedics. Rising consumer
demand for value-driven health care, new technology, and pain management
advancements, and more physicians training in minimally invasive surgical
techniques during their residency have driven this change. When a facility is
considering the establishment of an outpatient joint arthroplasty program,
leaders must take into consideration the outcomes data from the facility's
current joint arthroplasty program. Additional factors in establishing a
successful outpatient program include careful patient selection, preoperative
patient education, the presence of a case manager, and specialized protocols and
techniques.
PMID- 29953607
TI - Anterior cervical discectomy and fusion.
PMID- 29953606
TI - A Multidisciplinary Approach to Treating Traumatic Pelvic Fractures: 1.1
www.aornjournal.org/content/cme.
AB - Pelvic fractures are traumatic injuries that can be caused by motor vehicle
accidents, motorcycle accidents, motor vehicle-related pedestrian injuries, or
falls from a significant height. These injuries can be life threatening because
of the high vascularity of the pelvis and the difficulty in being able to see
bleeding occurring in this area. Traditional approaches to treat pelvic fractures
have been pelvic binding, external fixation, and open preperitoneal packing;
however, the use of angiography and embolization enables faster pinpointing of
the location of the bleeding. Increased use of hybrid ORs for treating traumatic
pelvic fractures combines the superior imaging of interventional radiology with
an OR that can quickly provide open interventions without needing to move a
patient from an interventional radiology suite to another OR. This improvement in
technology has combined the resources and knowledge of more diverse disciplines
to provide a more centralized approach to improving patient outcomes.
PMID- 29953608
TI - When Bullying Affects Patient Safety.
PMID- 29953611
TI - Guideline for design and maintenance of the surgical suite.
PMID- 29953610
TI - The Key to Safety: Communication.
PMID- 29953612
TI - AORN Position Statement on Orientation of the Registered Nurse and Surgical
Technologist to the Perioperative Setting.
PMID- 29953613
TI - Guideline Quick View: Instrument Cleaning.
PMID- 29953614
TI - Perrault LP, Kirkwood KA, Chang HL, et al. A prospective multi-institutional
cohort study of mediastinal infections after cardiac operations. Ann Thorac Surg.
2018;105(2):461-468.
PMID- 29953615
TI - An entirely enclosed scanning tunnelling microscope capable of being fully
immersed in liquid helium.
AB - We present an ultrahigh-vacuum (UHV)-sealed high-stability scanning tunnelling
microscope (STM) that can be entirely immersed in liquid helium and readily used
in a commercial Dewar or superconducting magnet. The STM head features a
horizontal microscanner that can become standalone and ultrastable when the
coarse approach inertial motor retracts. Low voltage is enough to operate the STM
even at low temperature owing to the powerful motor. It is housed in a tubular
chamber of 49 mm outer diameter, which can be pumped via a detachable valve (DV),
UHV-sealed and remain sealed after the DV is removed. The entire so-sealed
chamber can then be inserted into liquid helium, where in situ sample cleavage is
done via vacuum bellow. This allows sample cleavage and STM measurements to take
place in better UHV with higher cooling power. Quality atomic resolution images
of graphite and charge density wave on 1T-TiSe2 taken in ambient and 14 K
conditions, respectively, are presented.
PMID- 29953616
TI - Sca-1+ cardiac fibroblasts promote development of heart failure.
AB - The causative effect of GM-CSF produced by cardiac fibroblasts to development of
heart failure has not been shown. We identified the pathological GM-CSF-producing
cardiac fibroblast subset and the specific deletion of IL-17A signaling to these
cells attenuated cardiac inflammation and heart failure. We describe here the
CD45- CD31- CD29+ mEF-SK4+ PDGFRalpha+ Sca-1+ periostin+ (Sca-1+ ) cardiac
fibroblast subset as the main GM-CSF producer in both experimental autoimmune
myocarditis and myocardial infarction mouse models. Specific ablation of IL-17A
signaling to Sca-1+ periostin+ cardiac fibroblasts (PostnCre Il17rafl/fl )
protected mice from post-infarct heart failure and death. Moreover, PostnCre
Il17rafl/fl mice had significantly fewer GM-CSF-producing Sca-1+ cardiac
fibroblasts and inflammatory Ly6Chi monocytes in the heart. Sca-1+ cardiac
fibroblasts were not only potent GM-CSF producers, but also exhibited plasticity
and switched their cytokine production profiles depending on local
microenvironments. Moreover, we also found GM-CSF-positive cardiac fibroblasts in
cardiac biopsy samples from heart failure patients of myocarditis or ischemic
origin. Thus, this is the first identification of a pathological GM-CSF-producing
cardiac fibroblast subset in human and mice hearts with myocarditis and ischemic
cardiomyopathy. Sca-1+ cardiac fibroblasts direct the type of immune cells
infiltrating the heart during cardiac inflammation and drive the development of
heart failure.
PMID- 29953617
TI - HOXA11-AS promotes the growth and invasion of renal cancer by sponging miR-146b
5p to upregulate MMP16 expression.
AB - Recently, increasing studies showed that long noncoding RNAs (lncRNAs) play
critical roles in tumor progression. However, the function and underlying
mechanism of HOMEOBOX A11 antisense RNA (HOXA11-AS) on renal cancer remain
unclear. In the current study, our data showed that the expression of HOXA11-AS
was significantly upregulated in clear cell renal cell carcinoma (ccRCC) tissues
and cell lines. High HOXA11-AS expression was associated with the advanced
clinical stage, tumor stage, and lymph node metastasis. Function assays showed
that HOXA11-AS inhibition significantly suppressed renal cancer cells growth,
invasion, and ETM phenotype. In addition, underlying mechanism revealed that
HOXA11-AS could act as a competing endogenous RNA (ceRNA) that repressed miR-146b
5p expression, which regulated its downstream target MMP16 in renal cancer. Taken
together, our findings suggested that HOXA11-AS could promote renal cancer cells
growth and invasion by modulating miR-146b-5p-MMP16 axis. Thus, our findings
suggested that HOXA11-AS could serve as potential therapeutic target for the
treatment of renal cancer.
PMID- 29953618
TI - Acrolein-induced atherogenesis by stimulation of hepatic flavin containing
monooxygenase 3 and a protection from hydroxytyrosol.
AB - Acrolein, a highly toxic alpha, beta-unsaturated aldehyde, promotes the
progression of atherosclerosis in association with inflammatory signaling pathway
and reverse cholesterol transport (RCT) process. Additionally, hepatic flavin
containing monooxygenase 3 (FMO3) is involved in the pathogenesis of
atherosclerosis by regulating cholesterol metabolism. Hydroxytyrosol (HT), as a
major phenolic compound in olive oil, exerts anti-inflammatory and anti
atherogenic activities in vitro and animal models. The current study was designed
to evaluate whether FMO3 participated in pro-atherogenic process by acrolein and
HT showed protective effect during this process. Here, endothelial cells and
macrophage Raw264.7 cells were used as the cell models. Following oxidized low
density lipoprotein (OX-LDL) treatment, acrolein exposure promoted foam cells
formation in macrophage Raw264.7 cells. The expression of FMO3 and inflammatory
makers such as phospho-NF-kappaB, IL-1beta, TNFalpha as well as IL-6 were
significantly increased. However, ATP-binding cassette transporters subfamily A
member 1 (ABCA1), a major transporter in RCT process, was repressed by acrolein.
In addition, FMO3 knockdown could suppress inflammatory markers and promote ABCA1
expression. Hydroxytyrosol (HT) was observed to reduce lipid accumulation, FMO3
expression as well as inflammatory response. Moreover, it promoted ABCA1
expression. Therefore, our findings indicated that acrolein-enhanced
atherogenesis by increasing FMO3 which increased inflammatory responses and
decreased ABCA1 in vitro can be alleviated by HT, which may have a therapeutic
potential for the treatment of atherosclerosis.
PMID- 29953619
TI - Brain, antibiotics, and microbiota - how do they interplay?: An Editorial for
'Antibiotics-induced modulation of large intestinal microbiota altered aromatic
amino acid profile and expression of neurotransmitters in the hypothalamus of
piglets' on page 219.
AB - The microbiome and its cross-talk with the brain have drawn increasing attention
lately, since imbalances in the gut microbiota's composition may result in
pathogenic dysfunctions affecting brain functioning up to development of
neurodegenerative and mental diseases. The current Editorial discusses a study by
Gao and coworkers in the current issue of the Journal of Neurochemistry in which
the authors use a model of antibiotic-induced dysbiosis - targeted infusion of
antibiotics into the gut - to assess if microbiotic metabolites exert effects on
local neurotransmitter expression or contribute to the gut-brain axis. The
authors mechanistically link distal ileal infusion of antibiotics with a change
in the levels of microbial metabolites that affect the expression of
neurotransmitters in the brain and thereby can participate in the fine-tuning of
the hypothalamic functions, including regulation of visceral and neuroendocrine
processes, stress responses, mood and anxiety. Their study thus represents an
important step towards our understanding of the brain-gut axis, with the
potential to advance therapeutics.
PMID- 29953620
TI - Approaches to 3D printing teeth from X-ray microtomography.
AB - Artificial teeth have several advantages in preclinical training. The aim of this
study is to three-dimensionally (3D) print accurate artificial teeth using scans
from X-ray microtomography (XMT). Extracted and artificial teeth were imaged at
90 kV and 40 kV, respectively, to create detailed high contrast scans. The
dataset was visualised to produce internal and external meshes subsequently
exported to 3D modelling software for modification before finally sending to a
slicing program for printing. After appropriate parameter setting, the printer
deposited material in specific locations layer by layer, to create a 3D physical
model. Scans were manipulated to ensure a clean model was imported into the
slicing software, where layer height replicated the high spatial resolution that
was observed in the XMT scans. The model was then printed in two different
materials (polylactic acid and thermoplastic elastomer). A multimaterial print
was created to show the different physical characteristics between enamel and
dentine. LAY DESCRIPTION: Objectives Trainee dentists practice procedures using
artificial teeth that are far from real teeth. Using x-rays and 3D printing
technology the project will recreate a real tooth, artificially. Methods X-rays
produce a 3D image that can be printed out as a physical replica, after several
conversions of files. Different settings can be used to allow the printed model,
to be as accurate as possible. Data were collected on the forces from a dental
drill on a tooth's surface, to measure hardness and resistance. Results Multiple
teeth replicas were printed with a high accuracy. The materials printed did not
mimic actual tooth properties, but using the data from real teeth, materials can
be tested in future.
PMID- 29953621
TI - Assessing fluorescence detection and effective photothermal therapy of near
infrared polymer nanoparticles using alginate tissue phantoms.
AB - OBJECTIVE: Photothermal therapy (PTT) uses light absorbing materials to generate
heat for treatment of diseases, like cancer. The advantages of using PTT
components that absorb in the near-infrared (NIR) include reduced tissue auto
fluorescence and higher penetration depths. However, NIR laser light can still be
scattered and absorbed by biological tissues, thus decreasing the amount of the
energy reaching the PTT agents. We have developed two distinct formulations of
NIR-absorbing nanoparticles, one which can be utilized for PTT only, and another
for both PTT and fluorescence imaging of colorectal cancer. In this work, the
fluorescence detection limit and the PTT heating potential of the two
nanoparticle types were determined using alginate tissue phantoms. The objective
of this study was to determine the PTT efficiency and theranostic potential of
the nanoparticles by irradiating 3D collagen tumor spheroids, containing
nanoparticles and CT26 mouse colorectal cancer cells, through increasing tissue
phantom thicknesses and then quantifying cell death. Materials and Methods Our
lab has previously developed nanoparticles based on the semiconducting,
conjugated polymer poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b']dithiophene
2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). We have also made a
hybrid nanoparticle that heats and fluoresces by combining PCPDTBSe polymer with
the fluorescent poly[(9,9-dihexylfluorene)-co-2,1,3-benzothiadiazole-co-4,7
di(thiophen-2-yl)-2,1,3-benzothiadiazole] (PFBTDBT10) polymer to yield
nanoparticles termed Hybrid Donor-Acceptor Polymer Particles (H-DAPPs). H-DAPPs
and PCPDTBSe nanoparticles were added to three-dimensional collagen gel tumor
spheroids in order to represent nanoparticles in a tumor. Alginate tissue
phantoms, comprised of an optical scattering agent (Intralipid) and an optical
absorbing material (hemoglobin) in order to mirror biological tissue scattering
effects, were used to simulate increasing tissue thickness between the
nanoparticles and the PTT energy source. RESULTS: Fluorescence from the H-DAPPs
was detectable through 6 mm of tissue phantoms. It was found that less than 10%
of the laser energy could penetrate through 9 mm of tissue phantoms and only 60%
of the laser energy passed through the 1.5 mm phantoms, regardless of laser
power. PTT experiments, using 800 nm light at 2.2 W/cm2 for 60 s through tissue
phantoms to stimulate nanoparticle-doped tumor spheroids, showed 55% cell death
through 3 mm of tissue phantoms using H-DAPPs. Results from using the PCPDTBSe
nanoparticles showed 72% cell death through 3 mm and over 50% cell death through
6 mm of tissue phantoms. CONCLUSION: The results of this work validated the
heating potential and fluorescence detection limitations of two theranostic
polymer nanoparticles by utilizing alginate tissue phantoms and 3D tumor
spheroids. H-DAPPs and PCPDTBSe polymer nanoparticles can be utilized as
effective PTT agents by exploiting their absorption of NIR light and H-DAPPs have
advantageous fluorescence for imaging colorectal cancer. The data generated from
this study design can allow for other NIR absorbing and fluorescing nanoparticle
formulations to be evaluated prior to in vivo experimentation. Lasers Surg. Med.
(c) 2018 Wiley Periodicals, Inc.
PMID- 29953622
TI - Epidermal growth factor receptor and ligand family expression and activity in
glioblastoma.
AB - Epidermal growth factor family of receptor tyrosine kinases (ERBB) family cell
surface receptors, including epidermal growth factor receptor (EGFR/ERBB1), are
phosphorylated upon binding by various EGF family ligands and signal via multiple
kinase pathways. EGFR signaling is enhanced because of mutational activation of
EGFR in almost half of glioblastomas, the most common malignant primary brain
tumor. Therapeutic targeting of EGFR in glioblastoma has remained largely
unsuccessful. Here, we profiled nine long-term (LTC) and five glioma-initiating
(GIC) cell lines for expression and activation of ERBB family receptors and
expression of their ligands. Receptors and ligands were abundantly expressed,
with patterns overall similar to glioblastoma expression profiles in vivo as
deposited in The Cancer Genome Atlas database. No differences between LTC and GIC
emerged. Irrespective of ligand or receptor expression, neither an EGFR antibody,
erbitux, nor an EGFR tyrosine kinase inhibitor, gefitinib, were particularly
active against LTC or GIC at clinically relevant concentrations. Self-renewal
capacity of GIC was severely compromised by epidermal growth factor (EGF)
withdrawal, but rescued by transforming growth factor alpha (TGF-alpha), although
not by neuregulin-1 (NRG-1). Subcellular fractionation indicated high levels of
nuclear phosphorylated EGFR in all LTC and GIC. In LN-229 cells, pERBB2 and
pERBB3 were also detected in the nucleus. Nuclear pERBB2 was less sensitive,
whereas pERBB3 was induced, in response to gefitinib. This study provides an
extensive characterization of human glioma cell models, including stem-like
models, with regard to ERBB receptor/ligand expression and signaling. Redundant
signaling involving multiple ERBB family ligands and receptors may contribute to
the challenges of developing more effective EGFR-targeted therapies for
glioblastoma.
PMID- 29953623
TI - Impact of surgery in patients with metastatic soft tissue sarcoma: A monocentric
retrospective analysis.
AB - BACKGROUND AND OBJECTIVES: The role of local surgical procedures in patients with
metastatic soft tissue sarcoma is still undefined. Few retrospective studies have
reported survival benefits for patients with pulmonary metastases after complete
surgical resection. Treatment decisions are therefore mainly based on personal
experiences rather than on reproducible knowledge. METHOD: A total of 237
patients with metastatic sarcoma, treated between 1982 and 2015 at the University
Hospital Tuebingen, Germany, were eligible for inclusion. Out of the 237 screened
patients, 102 patients underwent at least one metastasectomy. Overall survival
was defined as the primary endpoint in this study. For association of non-linear
relationship to the endpoint, significant prognostic factors were included into a
recursive partitioning model. A subgroup analysis for long-term survivors was
also performed. RESULTS: The median overall survival was 64 months. The 3-, 5-,
10-, and 20-years overall survival rates were 70.7%, 50.3%, 24.7%, and 14.8%,
respectively. The number of resections and the progression-free intervals were
independent prognostic factors in three statistical models. CONCLUSION: Repeated
resections of metastases from different localizations are a strong predictor for
prolonged survival. We suggest that the progression-free interval after
metastasectomy should be considered as a predictive factor for benefit from
further surgery.
PMID- 29953625
TI - Choroidal remodeling after photodynamic therapy for polypoidal choroidal
vasculopathy.
PMID- 29953626
TI - A THERAPEUTIC PLAYGROUP FOR DEPRESSED MOTHERS AND THEIR INFANTS: FEASIBILITY
STUDY AND PILOT RANDOMIZED TRIAL OF COMMUNITY HUGS.
AB - Symptoms of depression negatively impact on mother-infant relationships and child
outcomes. We evaluated a novel, 10-session mother-infant therapeutic playgroup
Community HUGS (CHUGS)-which combines cognitive and experiential components
through psychoeducation, play, music, and movement. Participants were mothers
experiencing a range of postnatal mental health difficulties, including
depression, with infants <=12 months of age. However, the aim was not to treat
maternal depression but to ameliorate associated problems in the mother-infant
interaction. In the feasibility study, all participants received CHUGS. In the
pilot randomized controlled trial (RCT), participants were randomized between
intervention and a wait-list. Outcomes were the Parenting Stress Index (PSI; R.R.
Abidin, 1995), Parenting Sense of Competency Scale (Self-Efficacy subscale; J.
Gibaud-Wallston & L.P. Wandersman, 1978), and the Depression, Anxiety, Stress
Scales (P.F. Lovibond & S.H. Lovibond, 1995). In the feasibility study (n = 74),
PSI scores dropped on all subscales, all ps < .01. Depression, p < .001, anxiety,
p = .01, stress, p = .01, and self-efficacy, p < .001, all showed improvements,
as did observer-rated mother-infant interactions, p < .001. In the RCT,
depression, p < .001, anxiety, p = .005, and stress, p < .001, symptoms were
significantly reduced for intervention participants (n = 16), as compared to wait
list participants (n = 15). The CHUGS program had high participant satisfaction
and produced improvements in self-efficacy, depression, anxiety, stress, and
mother-infant interactions that supported the program's acceptability and the
utility of further rollout.
PMID- 29953624
TI - Coexistence of atrioventricular accessory pathways and drug-induced type 1
Brugada pattern.
AB - BACKGROUND: Atrial arrhythmias, particularly atrioventricular nodal reentrant
tachycardia, can coexist with drug-induced type 1 Brugada electrocardiogram (ECG)
pattern (DI-Type1-BrP). The present study was designed to determine the
prevalence of DI-Type1-BrP in patients with atrioventricular accessory pathways
(AV-APs) and to investigate the clinical, electrocardiographic,
electrophysiologic, and genetic characteristics of these patients. METHODS: One
hundred twenty-four consecutive cases of AV-APs and 84 controls underwent an
ajmaline challenge test to unmask DI-Type1-BrP. Genetic screening and analysis
was performed in 55 of the cases (19 with and 36 without DI-Type1-BrP). RESULTS:
Patients with AV-APs were significantly more likely than controls to have a Type1
BrP unmasked (16.1 vs 4.8%, P = 0.012). At baseline, patients with DI-Type1-BrP
had higher prevalence of chest pain, QR/rSr' pattern in V1 and QRS
notching/slurring in V2 and aVL during preexcitation, rSr' pattern in V1 -V2 ,
and QRS notching/slurring in aVL during orthodromic atrioventricular reentrant
tachycardia (AVRT) compared to patients without DI-Type1-BrP. Abnormal QRS
configuration (QRS notching/slurring and/or fragmentation) in V2 during
preexcitation was present in all patients with DI-Type1 BrP. The prevalence of
spontaneous preexcited atrial fibrillation (AF) and history of AF were similar
(15% vs 18.3%, P = 0.726) in patients with and without DI-Type1-BrP,
respectively. The prevalence of mutations in Brugada-susceptibility genes was
higher (36.8% vs 8.3%, P = 0.02) in patients with DI-Type1-BrP compared to
patients without DI-Type1-BrP. CONCLUSIONS: DI-Type1-BrP is relatively common in
patients with AV-APs. We identify 12-lead ECG characteristics during
preexcitation and orthodromic AVRT that point to an underlying type1-BrP,
portending an increased probability for development of malignant arrhythmias.
PMID- 29953627
TI - CAREGIVER SENSITIVITY AND CONSISTENCY AND CHILDREN'S PRIOR FAMILY EXPERIENCE AS
CONTEXTS FOR EARLY DEVELOPMENT WITHIN INSTITUTIONS.
AB - The current study addressed whether two institution-wide interventions in St.
Petersburg, Russian Federation, that increased caregiver sensitivity (Training
Only: TO) or both caregiver sensitivity and consistency (Training plus Structural
Changes: T+SC) promoted better socioemotional and cognitive development than did
a No Intervention (NoI) institution during the first year of life for children
who were placed soon after birth. It also assessed whether having spent less than
9 versus 9 to 36 months with a family prior to institutionalization was related
to children's subsequent socioemotional and cognitive development within these
three institutions. The Battelle Developmental Inventory (J. Newborg, J.R. Stock,
L. Wnek, J. Guidubaldi, & J. Svinicki, 1988) was used to assess the
socioemotional and cognitive functioning of children in NoI (n = 95), TO (n =
104), and T+SC (n = 86) at two to three time points during their first 6 to 12
months of residency. Results suggest that improving caregiver sensitivity can
improve the cognitive development of infants in the first year of
institutionalization whereas improving caregiver consistency in addition to
sensitivity is more beneficial for socioemotional development than is sensitivity
alone. Similarly, for children in T+SC, longer time with a family prior to
institutionalization (consistent caregiver, unknown sensitivity) was associated
with better socioemotional, but not cognitive, baseline scores and more rapid
cognitive than socioemotional development during institutionalization. These
results suggest caregiver sensitivity is more highly related to cognitive
development whereas caregiver consistency is more related to socioemotional
development in the first years of life.
PMID- 29953629
TI - Lung histopathology of non-infectious pulmonary complications after allogeneic
haematopoietic stem cell transplantation.
AB - AIMS: Non-infectious pulmonary complications (NIPCs) occur frequently following
allogeneic haematopoietic stem cell transplantation (HSCT). As there is no
consensus on the description of the related pulmonary pathological lesions,
pathologist reports and clinical conclusions are largely inconsistent in routine
practice. The aim of our study was to provide an accurate overview of post
allogeneic HSCT NIPCs from a large number of lung biopsies. METHODS AND RESULTS:
We reviewed 61 lung biopsies in patients with an NIPC, including 51 surgical lung
biopsies, four post-mortem biopsies and six lung explants. We found both
bronchiolar (n = 59) and alveolar/interstitial pathologies (n = 27). We describe
two types of bronchiolar lesions: bronchiolectasies (n = 37) and fibrous and
cellular lesions with luminal narrowing (n = 43). We found a wide spectrum of
airway/interstitial pathologies that were labelled using the terminology of the
2013 American Thoracic Society and European Respiratory Society (ATS/ERS)
classification of idiopathic interstitial pneumonias (IIPs), including the
following: organising pneumonia (OP, n = 8), non-specific interstitial pneumonia
(NSIP, n = 9), diffuse alveolar damage (DAD, n = 6), lymphoid interstitial
pneumonia (LIP, n = 1) and pleuroparenchymal fibroelastosis (PPFE, n = 2), as
well as one instance of associated PPFE and NSIP. CONCLUSIONS: Interstitial
pathology was associated with bronchiolar lesions in 41% of the cases reviewed (n
= 25). Lung airway and interstitial inflammation was still present in lung
explants from patients who underwent lung transplantation for post-allogeneic
HSCT end-stage respiratory insufficiency. Herein, we describe a wide spectrum of
pathological lung lesions encountered in post-allogeneic HSCT NIPCs.
PMID- 29953630
TI - Cryoablation of the right anteroseptal or midseptal accessory pathways in
children: A 2-year single-center experience.
AB - BACKGROUND: Radiofrequency catheter ablation (RFCA) in the septum close to the
atrioventricular node or His bundle has an increased risk of irreversible
complications. Cryothermal energy has the advantages of reversible cryomapping
and increased catheter stability. The study aims to evaluate the efficacy and
safety of cryoablation of the right anteroseptal or midseptal accessory pathways
(APs) in pediatric patients. METHOD: A retrospective review was performed with 26
pediatric patients (16 males and 10 females; median age 6.0 years and average
body weight 24.9 kg) with paroxysmal supraventricular tachycardia (PSVT) in our
Pediatric Heart Center from 2014 to 2016. Half of them had manifest APs. All the
children underwent cryoablation for the treatment of PSVT because of the right
anteroseptal or midseptal APs (16 cases had right anteroseptal APs and 10 cases
had right midseptal APs). RESULTS: Acute cryoablation success was achieved in 23
cases (88%, 23/26). Atrioventricular block (AVB) occurred in eight cases (31%,
8/26) during the procedures and normal atrioventricular conduction recovered in
seven cases except a case with I degrees AVB. During follow-up, three cases
recurred (13%, 3/23) and no permanent high degree AVB was found. CONCLUSION:
Cryoablation of the right anteroseptal or midseptal APs in pediatric patients is
both safe and effective.
PMID- 29953628
TI - Molecular Photoacoustic Contrast Agents: Design Principles & Applications.
AB - Photoacoustic imaging (PAI) is a rapidly growing field which offers high spatial
resolution and high contrast for deep-tissue imaging in vivo. PAI is nonionizing
and noninvasive and combines the optical resolution of fluorescence imaging with
the spatial resolution of ultrasound imaging. In particular, the development of
exogenous PA contrast agents has gained significant momentum of late with a
vastly expanding complexity of dye materials under investigation ranging from
small molecules to macromolecular proteins, polymeric and inorganic
nanoparticles. The goal of this review is to survey the current state of the art
in molecular photoacoustic contrast agents (MPACs) for applications in biomedical
imaging. The fundamental design principles of MPACs are presented and a review of
prior reports spanning from early-to-current literature is put forth.
PMID- 29953632
TI - Reopening the dialogue between the theory of social representations and
discursive psychology for examining the construction and transformation of
meaning in discourse and communication.
AB - The theory of social representations (TSR) and discursive psychology (DP)
originated as different social psychological approaches and have at times been
presented as incompatible. However, along the years convergence has also been
acknowledged, and, lately, most of all, practised. With this paper, we discuss
how versions of TSR focusing on self-other relations for examining cultural
meaning systems in/through communication, and versions of DP focusing on
discourse at cultural, ideological, and interactional levels, can come together.
The goal is to help forge a stronger social-psychological exploration of how
meaning is constructed and transformed in and through language, discourse, and
communication, thus extending current understanding of social change. After
presenting a theoretical proposal for integrating those versions of TSR and DP,
we offer also an integrated analytical strategy. We suggest that together these
proposals can, on one hand, help TSR systematize analyses of social change that
are both more critical and better grounded in theorizations of language use, and,
on the other, provide DP with analytical tools able to better examine both the
relational contexts where the construction and transformation of meaning are
performed and their effects on discourse. Finally, we give some illustrations of
the use of this analytical strategy.
PMID- 29953631
TI - Cannabis contaminants: sources, distribution, human toxicity and pharmacologic
effects.
AB - There has been a resurgence in interest and use of the cannabis plant for medical
purposes. However, an in-depth understanding of plant contaminants and toxin
effects on stability of plant compounds and human bioavailability is needed. This
systematic review aims to assess current understanding of the contaminants of
cannabis and their effect on human health, leading to the identification of
knowledge gaps for future investigation. A systematic search of seven indexed
biological and biomedical databases and the Cochrane library was undertaken from
inception up to December 2017. A qualitative synthesis of filtered results was
undertaken after independent assessment for eligibility by two reviewers. The
common cannabis contaminants include microbes, heavy metals and pesticides. Their
direct human toxicity is poorly quantified but include infection,
carcinogenicity, reproductive and developmental impacts. Cannabis dosing
formulations and administration routes affect the transformation and
bioavailability of contaminants. There may be important pharmacokinetic
interactions between the alkaloid active ingredients of cannabis (i.e.
phytocannabinoids) and contaminants but these are not yet identified nor
quantified. There is significant paucity in the literature describing the
prevalence and human impact of cannabis contaminants. Advances in the
availability of cannabis globally warrant further research in this area,
particularly when being used for patients.
PMID- 29953633
TI - Biosorption of malachite green onto Haematococcus pluvialis observed through
synchrotron Fourier-transform infrared microspectroscopy.
AB - : Microalgae have emerged as promising biosorbents for the treatment of malachite
green (MG) in wastewater. However, the underlying mechanism for the biosorption
of MG onto microalgae is still unclear and needs further intensive study. In this
work, synchrotron Fourier-transform infrared (s-FTIR) microspectroscopy in
combination with biochemical assay is employed to evaluate MG removal efficiency
(95.2%, 75.6% and 66.5%) by three stages of Haematococcus pluvialis. Meanwhile,
the various vital changes of algal cells including lipids, proteins,
polysaccharides and carotenoids is distinguished and quantified in situ. This
study illustrates that s-FTIR microspectroscopy is an effective and powerful tool
to scrutinize the mechanism for the interactions between the MG dye and
microalgal cells, and it even provides an effective and noninvasive new approach
to screen potentially proper biosorbents for the removal of dyes from wastewater.
SIGNIFICANCE AND IMPACT OF THE STUDY: Microalgae have potential application for
their ability to absorb dyes from industrial wastewater. In this study, we
initiated the application of synchrotron Fourier-transform infrared (s-FTIR)
microspectroscopy to investigate malachite green dye removal efficiency by three
stages of Haematococcus pluvialis, demonstrating that s-FTIR is a very powerful
tool in exploring the mechanism of the biosorption of dyes onto microalgae.
PMID- 29953634
TI - Endo-sinus bone formation after transalveolar sinus floor elevation without
grafting with simultaneous implant placement: Histological and histomorphometric
assessment in a dog model.
AB - AIM: To evaluate endo-sinus new bone formation and implant osseointegration after
transalveolar sinus floor elevation (TSFE) and simultaneous implant placement
without any grafting materials and to investigate the influence of implant
surface modification on bone healing process under this circumstance. MATERIALS
AND METHODS: Transalveolar sinus floor elevation and simultaneous implant
placement were conducted bilaterally on 12 Labrador dogs. No grafting materials
were used during surgery. Implants with two different surfaces (SLA and SLActive)
were placed in a split-mouth design. The animals were sacrificed 4, 8 and 24
weeks after surgery for histological and histomorphometric assessments. Bone-to
implant contact (BIC%), alveolar bone height (ABH) and the percentages of
mineralized bone (MB%) in the area of interest were analysed. The probing depth
(PD) and bleeding on probing (BOP) were also assessed to describe peri-implant
health conditions. RESULTS: Sprouts of new bone in direct contact with implant
surface were seen in the elevated area at every time point. Newly formed woven
bone under sinus membrane was visible. SLActive implants exhibited favourable
results compared with SLA implants regarding ABH at 4 weeks and BIC% at 4 and 8
weeks. Sites with BOP positive could be observed in both groups at any time
point. No newly formed bone can be found on the implant apex with either SLA or
SLActive surfaces at any time point. CONCLUSIONS: Spontaneous new bone formation
from the parent bone walls could be observed after TFE without any grafting
materials. No clear evidence of bone formation from the Schneiderian membrane
could be found. Even though there were trends for quicker bone response of
SLActive implants, this study failed to show the absolute advantage of SLActive
in achieving endo-sinus bone formation.
PMID- 29953636
TI - Comparative analysis of the blood transcriptomes between wolves and dogs.
AB - Dogs were domesticated by human and originated from wolves. Their evolutionary
relationships have attracted much scientific interest due to their genetic
affinity but different habitats. To identify the differences between dogs and
wolves associated with domestication, we analysed the blood transcriptomes of
wolves and dogs by RNA-Seq. We obtained a total of 30.87 Gb of raw reads from two
dogs and three wolves using RNA-Seq technology. Comparisons of the wolf and dog
transcriptomes revealed 524 genes differentially expressed genes between them. We
found that some genes related to immune function (DCK, ICAM4, GAPDH and BSG) and
aerobic capacity (HBA1, HBA2 and HBB) were more highly expressed in the wolf. Six
differentially expressed genes related to the innate immune response (CCL23,
TRIM10, DUSP10, RAB27A, CLEC5A and GCH1) were found in the wolf by a Gene
Ontology enrichment analysis. Immune system development was also enriched only in
the wolf group. The ALAS2, HMBS and FECH genes, shown to be enriched by the Kyoto
Encyclopedia of Genes and Genomes analysis, were associated with the higher
aerobic capacity and hypoxia endurance of the wolf. The results suggest that the
wolf might have greater resistance to pathogens, hypoxia endurance and aerobic
capacity than dogs do.
PMID- 29953635
TI - HCN channels in the hippocampus regulate active coping behavior.
AB - Active coping is an adaptive stress response that improves outcomes in medical
and neuropsychiatric diseases. To date, most research into coping style has
focused on neurotransmitter activity and little is known about the intrinsic
excitability of neurons in the associated brain regions that facilitate coping.
Previous studies have shown that HCN channels regulate neuronal excitability in
pyramidal cells and that HCN channel current (Ih ) in the CA1 area increases with
chronic mild stress. Reduction of Ih in the CA1 area leads to antidepressant-like
behavior, and this region has been implicated in the regulation of coping style.
We hypothesized that the antidepressant-like behavior achieved with CA1 knockdown
of Ih is accompanied by increases in active coping. In this report, we found that
global loss of TRIP8b, a necessary subunit for proper HCN channel localization in
pyramidal cells, led to active coping behavior in numerous assays specific to
coping style. We next employed a viral strategy using a dominant negative TRIP8b
isoform to alter coping behavior by reducing HCN channel expression. This
approach led to a robust reduction in Ih in CA1 pyramidal neurons and an increase
in active coping. Together, these results establish that changes in HCN channel
function in CA1 influences coping style.
PMID- 29953637
TI - Expression characteristics of long noncoding RNA uc.322 and its effects on
pancreatic islet function.
AB - Increasing evidence indicates that long noncoding RNAs (lncRNAs) perform special
biological functions by regulating gene expression through multiple pathways and
molecular mechanisms. The aim of this study was to explore the expression
characteristics of lncRNA uc.322 in pancreatic islet cells and its effects on the
secretion function of islet cells. Bioinformatics analysis was used to detect the
lncRNA uc.322 sequence, location, and structural features. Expression of lncRNA
uc.322 in different tissues was detected by quantitative polymerase chain
reaction analyses. Quantitative polymerase chain reaction, Western blot analysis,
adenosine triphosphate determination, glucose-stimulated insulin secretion, and
enzyme-linked immunosorbent assay were used to evaluate the effects of lncRNA
uc.322 on insulin secretion. The results showed that the full-length of lncRNA
uc.322 is 224 bp and that it is highly conserved in various species.
Bioinformatics analysis revealed that lncRNA uc.322 is located on chr7:122893196
122893419 (GRCH37/hg19) within the SRY-related HMG-box 6 gene exon region.
Compared with other tissues, lncRNA uc.322 is highly expressed in pancreatic
tissue. Upregulation of lncRNA uc.322 expression increases the insulin
transcription factors pancreatic and duodenal homeobox 1 and Forkhead box O1
expression, promotes insulin secretion in the extracellular fluid of Min6 cells,
and increases the adenosine triphosphate concentration. On the other hand,
knockdown of lncRNA uc.322 has opposite effects on Min6 cells. Overall, this
study showed that upregulation of lncRNA uc.322 in islet beta-cells can increase
the expression of insulin transcription factors and promote insulin secretion,
and it may be a new therapeutic target for diabetes.
PMID- 29953639
TI - What is lameness and what (or who) is the gold standard to detect it?
PMID- 29953640
TI - Anaesthesia-related equine fatalities: How good are we?
PMID- 29953638
TI - Maternal exercise in rats upregulates the placental insulin-like growth factor
system with diet- and sex-specific responses: minimal effects in mothers born
growth restricted.
AB - KEY POINTS: The placental insulin-like growth factor (IGF) system is critical for
normal fetoplacental growth, which is dysregulated following several pregnancy
perturbations including uteroplacental insufficiency and maternal obesity. We
report that the IGF system was altered in placentae of mothers born growth
restricted compared to normal birth weight mothers, with maternal diet- and fetal
sex-specific responses. Additionally, we report increased body weight and plasma
IGF1 concentrations in fetuses from chow-fed normal birth weight mothers that
exercised prior to and continued during pregnancy compared to sedentary mothers.
Exercise initiated during pregnancy, on the other hand, resulted in placental
morphological alterations and increased IGF1 and IGF1R protein expression, which
may in part be modulated by reduced Let 7f-1 miRNA abundance. Growth restriction
of mothers before birth and exercise differentially regulate the placental IGF
system with diet- and sex-specific responses, probably as a means to improve
fetoplacental growth and development, and hence neonatal survival. This increased
neonatal survival may prevent adult disease onset. ABSTRACT: The insulin-like
growth factor (IGF) system regulates fetoplacental growth and plays a role in
disease programming. Dysregulation of the IGF system is implicated in several
pregnancy perturbations associated with altered fetal growth, including
intrauterine growth restriction and maternal obesity. Limited human studies have
demonstrated that maternal exercise enhances fetoplacental growth and decreases
cord IGF ligands, which may restore the placental IGF system in complicated
pregnancies. This study investigated the impact maternal exercise has on the
placental IGF system in placentae from mothers born growth restricted and if
these outcomes are dependent on maternal diet or fetal sex. Uteroplacental
insufficiency (Restricted) or sham (Control) surgery was induced on embryonic day
(E) 18 in Wistar-Kyoto rats. F1 offspring were fed a chow or high-fat diet from
weaning, and at 16 weeks were randomly allocated an exercise protocol: Sedentary,
Exercised prior to and during pregnancy (Exercise), or Exercised during pregnancy
only (PregEx). Females were mated (20 weeks) with placentae associated with F2
fetuses collected at E20. The placental IGF system mRNA abundance and placental
morphology was altered in mothers born growth restricted. Exercise increased
fetal weight and Control plasma IGF1 concentrations, and decreased female
placental weight. PregEx did not influence fetoplacental growth but increased
placental IGF1 and IGF1R (potentially modulated by reduced Let 7f-1 miRNA) and
decreased placental IGF2 protein. Importantly, these placental IGF system changes
occurred with sex-specific responses. These data highlight that exercise
differently influences fetoplacental growth and the placental IGF system
depending on maternal exercise initiation, which may prevent the
transgenerational transmission of deficits and dysfunction.
PMID- 29953641
TI - OBSERVATION AND COMPARISON OF MEALTIME BEHAVIORS IN A SAMPLE OF CHILDREN WITH
AVOIDANT/RESTRICTIVE FOOD INTAKE DISORDERS AND A CONTROL SAMPLE OF CHILDREN WITH
TYPICAL DEVELOPMENT.
AB - Despite widespread use of behavioral observations to evaluate child feeding
behaviors in research and clinical practice, few studies have comprehensively
characterized mealtimes or identified features that differentiate children with
and without disordered feeding; these were the aims of the current study.
Mealtime observations were conducted for 18 children with avoidant restrictive
food intake disorder (ARFID) and 21 typically developing children. Observations
were coded inductively, and associations between disorder and observed mealtime
actions were examined. Most behaviors were observed across both clinical and
nonclinical mealtimes, and many did not differ in frequency between children with
and without ARFID. However, significant group differences were observed in the
frequencies of behaviors relating to food intake, visual and physical engagement
with feeding, and movement during mealtimes. The comparability of behaviors
across clinical and nonclinical groups suggests that eating behaviors exist on a
continuum from "normal" to "abnormal," with group differences relating to
frequency rather than type of behavior. The behavioral differences observed in
this study suggest that identification of children with ARFID should focus on
child engagement with food and restlessness during mealtimes. Reliance on
emotional and escape-maintained behaviors will lead to underrecognition of
families in need of clinical support.
PMID- 29953642
TI - FGF9 modulates Schwann cell myelination in developing nerves and induces a pro
inflammatory environment during injury.
AB - Myelin sheath is critical for the proper functioning of the peripheral nervous
system (PNS), which allows the effective conduction of nerve impulses. Fibroblast
growth factor 9 (FGF9) is an autocrine and paracrine protein in the fibroblast
growth factor family that regulates cell differentiation and proliferation. Fgf9
Schwann cell (SC) conditional knockout mice were developed to detect the role of
FGF9 in the PNS. In our study, the absence of Fgf9 led to delayed myelination in
early development. The expression of mature SC-related genes decreased, and the
expression of genes associated with immature SCs increased in the Fgf9 knockout
mice. These data were consistent with the morphology and praxeology we observed
during the development of the peripheral nerves. Extracellular-regulated kinases
1/2 (ERK1/2) are key signals for myelination, and our results showed that Fgf9
ablation led to the inactivation of ERK1/2. Further research was performed to
detect the role of FGF9 in peripheral nerve injury. In superoxide dismutase 1
G93A mice with Fgf9 SC knockout, we found that Fgf9 ablation inhibited the
expressions of Cd68, Il-1beta, and Cd86, which contributed to the degeneration of
the axon and myelin sheath.
PMID- 29953643
TI - Detecting a potential safety signal of antidepressants and type 2 diabetes: a
pharmacovigilance-pharmacodynamic study.
AB - AIMS: Recent data suggest that antidepressants are associated with incident
diabetes but the possible pharmacological mechanism is still questioned. The aim
of the present study was to evaluate antidepressant's risk for reporting diabetes
using disproportionality analysis of the FDA adverse events spontaneous reporting
system (FAERS) database and to investigate possible receptor/transporter
mechanisms involved. METHODS: Data from 2004 to 2017 were analysed using
OpenVigil2 and adjusted reporting odds ratio (aROR) for reporting diabetes was
calculated for 22 antidepressants. Events included in the narrow scope of the SMQ
'hyperglycaemia/new-onset diabetes mellitus' were defined as cases and all the
other events as non-cases. The pharmacodynamic profile was extracted using the
PDSP and IUPHAR/BPS databases and the occupancy on receptors (serotonin, alpha
adrenoreceptors, dopamine, muscarinic, histamine) and transporters (SERT, NET,
DAT) was estimated. The relationship between aROR for diabetes and receptor
occupancy was investigated with Pearson's correlation coefficient (r) and
univariate linear regression. RESULTS: Six antidepressants were associated with
diabetes: nortriptyline with aROR [95% CI] of 2.01 [1.41-2.87], doxepin 1.97
[1.31-2.97], imipramine 1.82 [1.09-3.06], sertraline 1.47 [1.29-1.68],
mirtazapine 1.33 [1.04-1.69] and amitriptyline 1.31 [1.09-1.59]. Strong positive
correlation coefficients between occupancy and aROR for diabetes were identified
for the receptors M1 , M3 , M4 , M5 and H1 . CONCLUSION: Most of the tricyclic
antidepressants, mirtazapine and sertraline seem to be associated with reporting
diabetes in FAERS. Higher degrees of occupancy on muscarinic receptors and H1 may
be a plausible pharmacological mechanism. Further clinical assessment and
pharmacovigilance data is needed to validate this potential safety signal.
PMID- 29953644
TI - Physiological stretch induced proliferation of human urothelial cells via
integrin alpha6-FAK signaling pathway.
AB - AIMS: To test a kind of stretch pattern which is the optimum stress parameter to
promote human urothelial cells (HUCs) proliferation, and to investigate the roles
of integrin subunits and their pathway in the HUCs proliferation induced by
physiological stretch. METHODS: HUCs were seeded on silicone membrane, and
subjected to four kinds of stretch (0,5%,10%,15% elongation) for 24 h, as
controlled by a BioDynamic(r) bioreactor. Cell proliferation, viability and cycle
distribution were examined using Cell Counting Kit-8 and flow cytometry,
respectively. The gene and protein expression of integrin subunits and focal
adhesion kinase (FAK) in each group were assessed by Real-time PCR(RT-PCR) and
western blot, respectively. Small interfering RNAs (siRNA) were applied to
knockdown integrin alpha6 and FAK expression in HUCs, and FAK inhibitor was used
to validate the role of alpha6 and FAK in cell proliferation under physiological
stretch. RESULTS: The proliferation of HUCs were highest in the 5% elongation
group compared to static control, 10% and 15% elongation group. RT-PCR and
western blot showed that 5% cyclic stretch significantly promoted the expression
of integrin alpha6 and FAK. The stretch-induced cell proliferation and FAK
expression was inhibited by siRNA of integrin alpha6. Further study with FAK
inhibitor revealed that elongation promoted proliferation though integrin alpha6
and FAK signaling pathway. CONCLUSIONS: Physiological stretch induced HUCs
proliferation via integrin alpha6-FAK signaling pathway, and 5% elongation may be
the optimal stress parameter to promote the cell proliferation.
PMID- 29953645
TI - Long noncoding RNA GIHCG enhanced tongue squamous cell carcinoma progression
through regulating miR-429.
AB - Long noncoding RNAs play essential roles in cancer development and progression.
Here, we tried to investigate the role of GIHCG in the progression and metastasis
of tongue squamous cell carcinoma (TSCC). In our study, we showed that that the
expression level of GIHCG was upregulated in TSCC tissues and cell lines. In
addition, we indicated that high GIHCG expression was positively associated with
poor overall survival. Moreover, ectopic expression of GIHCG enhanced TSCC cell
cycle, proliferation, and migration. Elevated expression of GIHCG inhibited the
miR-429 expression in TSCC cells. We demonstrated that the expression level of
miR-429 was lower in TSCC tissues and cell lines. Low miR-429 expression was
positively associated with poor overall survival. We then determined the
correlation between miR-429 and GIHCG expression levels. A statistically
significantly inverse correlation was observed between miR-429 and GIHCG
expression levels in TSCC tissues. In addition, overexpression of miR-429
suppressed the TSCC cell cycle, proliferation, and migration. Elevated expression
of GIHCG promoted TSCC cell cycle, proliferation, and migration through
regulating miR-429 expression. These results suggested that GIHCG increased TSCC
progression through negative modulation of miR-429. Our results suggested that
GIHCG/miR-429 might play a vital role in TSCC progression.
PMID- 29953646
TI - Positive correlation between vitamin D receptor gene FokI polymorphism and
colorectal cancer susceptibility in South-Khorasan of Iran.
AB - Colorectal cancer (CRC) is a global public health problem. Despite the major
milestone in early diagnosis and treatment of colorectal cancer, the prevalence
of CRC rates is still rising. The etiology of CRC is still unknown but we know
CRC is influenced by both of environment and genetic factors. In this study, we
aimed to elucidate the role of vitamin D receptor gene polymorphic regions; FokI
and TaqI single nucleotide polymorphisms, in increasing the risk of colorectal
cancer in Birjand population. One hundred patients with CRC and 100 healthy
controls recruited to the study. Genotyping was performed by PCR-RFLP
(restriction fragment length polymorphism) method technique for all individuals.
There were statistically significant differences between ff genotype and f allele
of FokI SNP in case and control groups. Our results manifested positive
correlation between ff genotype and f allele of FokI SNP with colorectal cancer
predisposition (P = 0.035, P = 0.0001 respectively) in South Khorasan population.
The present study showed that FokI polymorphism but not TaqI polymorphism may
contribute to CRC susceptibility. In addition, ff genotype of FokI polymorphism
was associated with CRC risk.
PMID- 29953647
TI - Mir-1287 suppresses the proliferation, invasion, and migration in hepatocellular
carcinoma by targeting PIK3R3.
AB - Mature microRNAs (miRNAs) are a class of small noncoding RNA molecules involved
in regulation of post-translational gene expression. Although aberrant levels of
miRNAs have been found in various tumor tissues, their importance in tumor
development and the molecular basis of their regulatory role remain unclear. Our
bioinformatic analysis on The Cancer Genome Atlas database and microarray-based
comparison of miRNA in different cell lines revealed that the level of mir-1287
is suppressed in hepatocellular carcinoma (HCC) cells. When upregulated, mir-1287
can reduce the tumorigenesis phenotypes of HCC cells in several in vitro models.
We further found that mir-1287 directly targets messenger RNA encoding PIK3R3,
which is a tumor-promoting factor acting in several pathways linked to
tumorigenesis. Our study suggests that aberrant suppression of mir-1287 is
potentially responsible for the development of HCC, and miRNA-based strategies
may be developed for efficient detection and treatment of HCC.
PMID- 29953648
TI - microRNA-146a is involved in rSjP40-inhibited activation of LX-2 cells by
targeting Smad4 expression.
AB - Previous studies have demonstrated that the recombinant Schistosoma japonicum
protein P40 (rSjP40) could inhibit activation of hepatic stellate cells (HSCs)
through the TGF-beta1/Smads signaling pathway. Since multiple microRNAs could
play essential roles in HSC activation and in the process of hepatic fibrosis
through targeting Smads, we attempted to seek the potential microRNAs that could
be involved in rSjP40-induced inhibition of HSC activation. Using the method of
quantitative real-time PCR, we found that rSjP40 could induce miR-146a expression
in LX-2 cells. The down-regulated expression levels of Smad4 and alpha-SMA in LX
2 cells induced by rSjP40 were partially restored by an miR-146a inhibitor. miR
146a can be involved in rSjP40-induced inhibition of HSC activation through
targeting Smad4. These findings provide us a new idea to explore the potential
mechanisms by which rSjP40 could regulate the process of hepatic fibrosis.
PMID- 29953649
TI - Long noncoding RNA-RNCR3 overexpression deleteriously affects the growth of
glioblastoma cells through miR-185-5p/Kruppel-like factor 16 axis.
AB - Glioblastoma (GBM) is a devastating and highly aggressive tumor, which is
apoptosis resistant and difficult to cure. Recently, long noncoding RNAs have
been shown to play a pivotal role in GBM progression. Evidence has suggested that
retinal noncoding RNA3 (RNCR3) is a GBM-associated noncoding RNA and is under
expressed in GBM. However, the function and mechanism of RNCR3 on GBM cell growth
and apoptosis are still uncertain. In the current study, we found that the level
of RNCR3 is decreased in U87, U251, U373, and A172 GBM cell lines when compared
with the normal human astrocytes. Elevating long noncoding RNA RNCR3 expression
markedly inhibits U87 and U251 cell survival and proliferation. Further studies
indicated that RNCR3 overexpression promotes U87 and U251 cell apoptosis and
activity caspase-3/7. Moreover, we found that RNCR3 overexpression promotes
Kruppel-like factor 16 (KLF16) expression through inhibiting the level of miR-185
5p. We demonstrated that KLF16 is a direct target of miR-185-5p. An increased miR
185-5p level by a miR-185-5p mimic or decreased KLF16 by KLF16 small interfering
RNA both reversed the function of RNCR3 overexpression on GBM cell growth and
apoptosis. In summary, this study focuses on investigating the key molecular
mechanisms of RNCR3 involved in GBM cell growth and apoptosis. Our data indicated
that RNCR3 overexpression inhibits cell growth and induces its apoptosis through
the miR-185-5p/KLF16 axis.
PMID- 29953650
TI - Suture causing urethral meatus stricture: A novel animal model of partial bladder
outlet obstruction.
AB - AIMS: Open surgery is the most commonly used methodological approach for
generating a partial bladder outlet obstruction (pBOO) animal model. Surgical
suturing closing a part of the urethral meatus induces comparable
pathophysiological changes in bladder and renal functions, but the optimum degree
of obstruction that closely mimics the clinical pathology of pBOO has not been
elucidated. We investigated the optimum obstruction level by performing a
comprehensive time-dependent analysis of the stability and reliability of this
novel animal model. METHODS: Six- to eight-week-old female BALB/c mice were
divided into three groups according to the degree of urethral meatus stricture
(UMS). Non-operated mice served as controls, and a pBOO model generated using the
traditional method served as a positive control. A cystometric evaluation and
long-term studies were performed to evaluate the validity and reliability of this
novel animal model. An additional 35 mice were used to investigate the protein
expression levels and histopathological features 24 h and 14 days
postoperatively, respectively. RESULTS: The characteristic cystometry features in
the UMS group revealed increased changes in pressure-related parameters compared
with the control. The 1/3 UMS model is an optional pBOO animal model because the
cystometric evaluation and histopathological studies revealed a striking
resemblance between the 1/3 UMS model and the model generated using the
traditional open-surgery method. CONCLUSIONS: The minimally invasive UMS model
required less time and produced minimal alterations in pathophysiologically
relevant processes compared with the traditional surgery model. Suturing to cause
UMS produced effective and repeatable patterns in bladder function investigations
in mice.
PMID- 29953651
TI - MicroRNA-19 restores vascular endothelial cell function in lower limb ischemia
reperfusion injury through the KLF10-dependent TGF-beta1/Smad signaling pathway
in rats.
AB - Ischemia-reperfusion injury (IRI) is a severe problem patients diagnosed with
acute limb ischemia. Recently, microRNAs (miR) have emerged as regulators of IRI
as well as ischemic preconditioning and ischemic postconditioning. Therefore,
using rat models, this study aims to explore all of the possible mechanisms that
miR-19 exhibits with its relation to the transforming growth factor beta (TGF
beta1)/Smad signaling pathway in the lower limb IRI. An immunofluorescence
staining method was used to identify the Krueppel-like factor 10 (KLF10) positive
expression and the location of KLF10 expression. The targeting relationship that
miR-19 has with KLF10 was verified by the dual-luciferase reporter gene assay.
Vascular endothelial cells (VECs) were treated with elevated or suppressed miR-19
or KLF10 knockdown. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium
bromide assay was used to test cell proliferation, and flow cytometry was
employed to detect both cell cycle and apoptosis. The KLF10-positive expression
in the VECs (both in cytoplasm and nucleus) was found to be elevated in the IRI
rats. We found that miR-19 was downregulated, KLF10 upregulated, and the TGF
beta1/Smad signaling pathway activated in the vascular epithelial tissues of IRI
rats. KLF10 is a target gene of miR-19. Overexpression of miR-19 decreased the
expression of KLF10, TGF-beta1, and Smad2/3. Decreased miR-19 inhibited VEC
proliferation, arrested VECs at the G1 phase, and promoted the apoptosis of VECs
following their lower limb I/R injury. These results indicate miR-19 as being an
inhibitor in the VEC injury of IRI via the TGF-beta1/Smad signaling pathway by
suppression of KLF10.
PMID- 29953652
TI - Comments on "Reconstruction of an upper posterior thigh extensive defect with a
free split-anterolateral thigh (s-ALT) flap by perforator-to-perforator
anastomosis: A case report".
PMID- 29953653
TI - Valproic acid inhibits the protective effects of stromal cells against
chemotherapy in breast cancer: Insights from proteomics and systems biology.
AB - Interaction between tumor and stromal cells is beginning to be decoded as a
contributor to chemotherapy resistance. Here, we aim to take a system-level
approach to explore a mechanism by which stromal cells induce chemoresistance in
cancer cells and subsequently identify a drug that can inhibit such interaction.
Using a proteomic dataset containing quantitative data on secretome of stromal
cells, we performed multivariate analyses and found that bone-marrow mesenchymal
stem cells (BM-MSCs) play the most protective role against chemotherapeutics.
Pathway enrichment tests showed that secreted cytokines from BM-MSCs activated 4
signaling pathways including Janus kinase-signal transducer and activator of
transcription, phosphatidylinositol 3-kinase-protein kinase B, and mitogen
activated protein kinase, transforming growth factor-beta in cancer cells
collectively leading to nuclear factor kappa-light-chain-enhancer of activated B
cells (NF-kB) transcription factor activation. Based on the data from integrated
Library of Integrated Network-Based Cellular Signatures (iLINCs) program, we
found that among different drugs, valproic acid (VA) affected the expression of
34 genes within the identified pathways that are activated by stromal cells. Our
in vitro experiments confirmed that VA inhibits NF-kB activation in cancer cells.
In addition, analyzing gene expression data in patients taking oral VA showed
that this drug decreased expression of antioxidant enzymes culminating in
increased oxidative stress in tumor cells. These results suggest that VA confines
the protective role of stromal cells by inhibiting the adaptation mechanisms
toward oxidative stress which is potentiated by stromal cells. Since VA is an
already prescribed drug manifesting anticancer effects, this study provides a
mechanistic insight for combination of VA with chemotherapy in the clinical
setting.
PMID- 29953654
TI - Myelomeningocele closure by unilateral lumbar artery perforator flap: Experience
with thirty-eight patients.
AB - BACKGROUND: Repair of large soft tissue defects in meningomyelocele is difficult
and its morbidity is high. By applying unilateral lumbar artery perforator
transposition flap for closing these defects, we aimed to investigate effects on
the repair procedure, duration of surgery and recovery period, with the rates of
bleeding and morbidity. PATIENTS AND METHODS: Our report was conducted in 38
patients between the years 2013 and 2017. All soft tissue defects were repaired
with unilateral lumbar artery perforator flap (LAPF) in meningomyelocele.
Fourteen patients were female and 24 patients were male. The youngest patient was
a 5.5 month premature female baby and weighing 570 g. The oldest was weighing
3,700 g and at 1.5 months old. RESULTS: Mean flap size was 32 +/- 29.4 cm2
(ranged: 4 * 3-8 * 7 cm2 ). The mean rotation angle was 126.7 degrees (ranged:
90 degrees -170 degrees ). Flap positions were separated as 9 (23%) thoracodorsal
and 29 (77%) lumbosacral. None of the patients had flap necrosis, infection, or
hematoma. The operation took 23 +/- 5.3 minutes on average and bleeding was
minimal as 16 cc. All patients were discharged within around 9 +/- 2 days. The
follow-up period of the patient ranged from 4 to 21 months. Flap survival was at
the rate of 100%. There was no flap or postoperative complications. Final outcome
for all patients were assessed as complete healing. All patients recovered fast
with minimal blood lose, and satisfied the outcomes. CONCLUSIONS: As a result,
unilateral lumbar perforator flap can be performed successfully in every center.
This report suggests using LAPF for reconstruction of meningomyelocele by
surgeons as a safe and reliable option, allowing surgeons strong results.
PMID- 29953655
TI - Downregulation of IL-22 can be considered as a risk factor for onset of type 2
diabetes.
AB - There is some controversy as for the roles played by tumor growth factor-beta
(TGF-beta), interleukin-1beta (IL-1beta), and IL-22 in the onset process of type
2 diabetes (T2D). The main aim of this project was to examine serum levels of TGF
beta, IL-1beta, and IL-22 in the new cases and long period T2D patients as well
as healthy controls. In this study, 115 new T2D patient cases (group 1), 434 T2D
patients who have suffered from the disease more than 2 years (group 2), and 104
healthy controls have been selected from 6240 (3619 females) patients who were
under study population from Kerman Coronary Artery Disease Risk Factor Study.
Serum levels of TGF-beta, IL-1beta, and IL-22 have been evaluated using
commercial kits. Serum levels of TGF-beta and IL-1beta significantly increased,
while IL-22 decreased in 2 groups in comparison to healthy controls. Serum levels
of IL-22, but not TGF-beta and IL-1beta, were significantly decreased in group 1
in comparison to healthy controls. There were no significant differences between
groups 1 and 2 as for the cytokine levels. Serum levels of IL-22 increased in the
females in group 2 when compared to females in group 1. It appears that TGF-beta
and IL-1beta participate in the induction of inflammation after establishment of
T2D, while decrease in IL-22 may be considered as a key factor for onset of the
disease. Gender can also be considered as the main risk factor for variation in
cytokine levels.
PMID- 29953656
TI - Is the infusion of Plasma-Lyte 148 and 5% Glucose into peripheral veins really
problematic?
PMID- 29953657
TI - Impact of lower urinary tract symptoms on work productivity in female workers: A
systematic review and meta-analysis.
AB - AIMS: The aim of this systematic review and meta-analysis was to determine the
impact of lower urinary tract symptoms (LUTS) on work productivity in female
workers. METHODS: A comprehensive literature search was conducted using eight
electronic databases (MEDLINE, PEDro, CINAHL, Cochrane library, EMBASE, PubMed,
Scopus, and PsycINFO) to identify articles published before July 2017 that
studied the work productivity in female workers with LUTS. Two reviewers
independently assessed the quality of studies using the Joanna Briggs Institute.
Meta-analyses were performed on studies having measured work productivity between
females with and without LUTS, and odds ratios (ORs) or the mean differences were
used. RESULTS: Fourteen articles (n = 48 223 females) were included in the
review, and meta-analyses were performed with six of those articles. Lower
urinary tract symptoms were significantly associated with work productivity loss
(OR = 1.11, 95%CI = 1.06-1.15), presenteeism (OR = 1.10, 95%CI = 1.05-1.14), and
activity impairment (OR = 1.11, 95%CI = 1.09-1.14). However, there was no
significant difference in the probability of absenteeism between females with and
without LUTS (OR = 1.03, 95%CI = 0.94-1.13). CONCLUSIONS: Evidence suggests that
female workers with LUTS had significantly greater work productivity impairment
compared to those without LUTS.
PMID- 29953658
TI - Re: Gammie A et al: Signs and symptoms that distinguish detrusor underactivity
from mixed detrusor underactivity and bladder outlet obstruction in male
patients.
PMID- 29953659
TI - Why ICS standardization of lower urinary tract symptoms matters.
AB - Notice of Withdrawal: Why ICS standardization of lower urinary tract symptoms
matters by Dirk De Ridder and Marcus Drake The Editorial Comment "Why ICS
standardization of lower urinary tract symptoms matters" published online 28 June
2018 in Wiley Online Library (wileyonlinelibrary.com), has been temporarily
withdrawn by agreement between the journal editorial office and Wiley
Periodicals, Inc. The withdrawal has been agreed because the article will publish
in final form in the Neurourology and Urodynamics special issue, Fundamental
Assessment of Lower Urinary Tract Dysfunction, that will publish in August 2018.
PMID- 29953660
TI - New technology assessment and current and upcoming therapies for underactive
bladder.
AB - BACKGROUND AND AIMS: Stakeholders from around the world came together to address
the unmet needs of underactive bladder (UAB) at the 3rd International Congress
for Underactive Bladder. METHODS: The main recommendation from the regulatory
working group is a need for a meeting of UAB stakeholders and regulatory agencies
including the FDA to discuss guidance for regulatory trial design for devices,
drugs, and/or biologics for UAB. RESULTS: The following issues to be discussed
and agreed upon for UAB trials: 1) Appropriate inclusion and exclusion criteria.
2) Should residual urine volume be the primary outcome parameter and how often
should it be measured? 3) Are there secondary measures that should have a place
in UAB trials, such as change in the number of catheterizations, quality of life
measures, etc.? 4) Use and format of bladder voiding and catheterization diary
for trials. 5) Define role and technique of urodynamics in UAB trials. Are
urodynamics required to monitor, and possibly exclude, individuals with high
pressure voiding induced by bladder prokinetic therapies? 6) Development and use
of UAB questionnaires. DISCUSSION AND CONCLUSION: The UAB regulatory working
group recognizes the path forward should include engaging the FDA and other
regulatory organizations that may harmonize and formalize guidance for regulatory
trial designs for therapeutics for UAB.
PMID- 29953661
TI - Full oral feeding is possible before discharge even in extremely preterm infants.
AB - AIM: This study described the steps needed to achieve full oral feeding before
discharge in a group of very and extremely preterm (EPT) infants. We analysed the
effects of oral feeding skills on discharge timing and on weight gain during
their neonatal intensive care unit (NICU) stay. METHODS: A prospective cross
sectional observational study of 100 infants who were <32 weeks of gestation (GA)
was conducted at the Division of Neonatology, Graz, Austria, from March 2014 to
February 2015. Patients were stratified into two groups: those who were <28 weeks
at birth and those who were 28 weeks and over. Velocity of oral feeding skills
attainment and weight gain were analysed. RESULTS: All infants successfully
acquired oral feeding skills during hospitalisation. The median GA at which full
oral feeding skills were reached was 37 + 1 weeks in EPT and 34 + 5 weeks in very
preterm infants. More immature neonates showed worse feeding performances and
lower weight increments during oral feeding steps. CONCLUSION: Our study
confirmed the role of GA in the development of oral feeding skills in the most
premature babies. It also raises the question of whether expected daily weight
gain should be targeted according to GA.
PMID- 29953662
TI - Association between the frequency of bedwetting and late preterm birth in
children aged >=5 years.
AB - AIM: We examined the associations between late preterm (LPT) birth children aged
>=5 years and the frequency of bedwetting. Moreover, those who were born full
term/low birthweight (BW), LPT/low BW, LPT/normal BW and LPT/low BW were
compared. METHODS: In total, we evaluated 614 patients who underwent assessments
for frequent bedwetting at the three hospitals from January 2014 to December
2016. Data at the initial visit were collected from the electronic medical
records. We assessed the patients' bladder diaries and questionnaires containing
detailed information on demographics and frequency of bedwetting per month.
Neonatal data were collected from the Maternal and Child Health Handbook.
RESULTS: Frequency of bedwetting in the LPT/low BW group was higher than in the
term/low BW group (28 vs. 22.5, p < 0.05). However, the frequency between the
LPT/normal BW group and the LPT/low BW group was not significantly different (28
vs. 28, p = 1.00). Multiple regression analyses were conducted to eliminate
potential confounding factors, attention-deficit/hyperactivity disorder and
intellectual disability, but results were not changed. CONCLUSION: This study
revealed that LPT/low BW was associated with increased frequency of bedwetting in
children. The results suggest that gestational age should be considered when
examining patients with severe bedwetting.
PMID- 29953663
TI - Differences in cost consciousness between physicians and nurses in German
neonatal intensive care units.
AB - AIM: This study assessed the cost consciousness of nurses and physicians in
German neonatal intensive care units (NICUs) and identified factors affecting
cost consciousness. METHODS: This study on cost consciousness was part of the
German Safety4NICU study, a cross-sectional survey conducted from 2015 to 2016.
All 224 German NICUs were invited to take part in the survey, and written consent
was obtained from the leading physicians and nurses. The various professions were
addressed via specific questionnaires. The cost survey tool identified the
participants' responsibility and their desired focus on cost consciousness.
RESULTS: Of the 1406 nurses and 496 physicians from 84 NICUs, 64.4% of the nurses
and 62.5% of the physicians agreed that they shared responsibility for
controlling costs. The computed score to define the overall cost consciousness
level was 4.47. We identified a significantly positive association between cost
consciousness, longer total clinical work experience and a decreased number of
NICU intensive care beds. Increased cost consciousness was found in both men and
physicians. Other hospital characteristics did not have an effect. CONCLUSION:
Neonatology is a medical speciality where the tension between economics and the
benefit of patients is extremely high. We found a moderate level of cost
consciousness among NICU physicians and nurses.
PMID- 29953664
TI - The Emperor's New Clothes: What Randomized Controlled Trials Don't Cover.
PMID- 29953665
TI - Diazoxide ameliorates severity of experimental osteoarthritis by activating
autophagy via modulation of the osteoarthritis-related biomarkers.
AB - Accumulating evidence suggests that autophagy plays a protective role in
chondrocytes and prevents cartilage degeneration in osteoarthritis (OA). The
objective of this study was to investigate the effect of diazoxide on chondrocyte
death and cartilage degeneration and to determine whether these effects are
correlated to autophagy in experimental OA. In this study, a cellular OA model
was established by stimulating SW1353 cells with interleukin 1beta. A rat OA
model was generated by transecting the anterior cruciate ligament combined with
the resection of the medial menisci, followed by treatment with diazoxide or
diazoxide combination with 3-methyladenine. The percentage of viable cells was
evaluated using calcein-acetoxymethyl/propidium iodide double staining. The
messenger RNA expression levels of collagen type II alpha 1 chain (COL2A1),
matrix metalloproteinase 13 (MMP-13), TIMP metallopeptidase inhibitor 1 (TIMP-1),
and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5)
were determined using quantitative real-time polymerase chain reaction. The
cartilage thickness and joint space were evaluated using ultrasound. SW1353 cell
degeneration and autophagosomes were observed using transmission electron
microscopy. The expression levels of microtubule-associated protein 1 light chain
3 (LC3), beclin-1, P62, COL2A1, and MMP-13 were evaluated using
immunofluorescence staining and Western blot analysis. Diazoxide significantly
attenuated articular cartilage degeneration and SW1353 cell death in experimental
OA. The restoration of autophagy was observed in the diazoxide-treated group. The
beneficial effects of diazoxide were markedly blocked by 3-methyladenine.
Diazoxide treatment also modulated the expression levels of OA-related
biomarkers. These results demonstrated that diazoxide exerted a chondroprotective
effect and attenuated cartilage degeneration by restoring autophagy via
modulation of OA-related biomarkers in experimental OA. Diazoxide treatment might
be a promising therapeutic approach to prevent the development of OA.
PMID- 29953666
TI - Intermittent Catheterization Adherence Scale (ICAS): A new tool for the
evaluation of patient adherence with clean intermittent self-catheterization.
AB - AIM: Patients who have successfully acquired the intermittent self
catheterization (ISC) technique can be expected to use it on a long-term basis.
The aim of the present study is to present a validated evaluation scale, referred
to as the ICAS (Intermittent Catheterization Adherence Scale), which can be used
to assess long-term patient adherence to prescribed ISC treatment. METHODS: The
scale was validated in neurologic and non neurologic patients in an experienced
French neurourology center, between September 2014 and February 2016. Eight items
were chosen, providing a relatively objective insight into the degree to which
patients reduce the frequency of their ISC procedures. Various factors, including
the patients' understanding of the procedure, its relevance to their specific
condition, as well as their acceptance of its psychological and inherently time
consuming drawbacks, were evaluated. The ISC construct validity and
reproducibility, based on internal test-retest consistency and test-retest
reliability, were measured using the Intra-class Correlation Coefficient (ICC).
RESULTS: The ICAS was validated in 222 patients (133 females, 89 males, mean age
53 +/- 11 years). The patients' comprehension of the questions was found to be
good, and the questionnaire was well accepted. Cronbach's alpha was 0.73. The ICC
test-retest consistency was also found to be good. CONCLUSION: The ICAS is a
simple, acceptable, valid and reproducible test, and in some cases it may
facilitate the medical follow-up of ISC patients. In the clinical environment, it
is found to be a valuable tool, which can assist medical staff in the prevention
of complications related to ISC non-compliance.
PMID- 29953667
TI - Photoonycholysis: new findings.
AB - First described in 1961, photoonycholysis (PO) is a rare nail alteration that may
result from drug intake, from topical aminolevulinate photodynamic therapy or
from photosensitive conditions such as porphyria or pseudoporphyria. Spontaneous
PO is rare. This review updates the numerous causes of PO and highlights some new
ways producing this condition. Four different types of PO are clearly recognized
without relationship with the responsible drug. An updated list of potential
inducing drug is provided. Some practical points on PO have been raised. The
inability to reproduce photoonycholysis experimentally should be emphasized, and
the pathogenesis of PO still needs to be clarified.
PMID- 29953668
TI - Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild
cognitive impairment.
AB - OBJECTIVES: To investigate the association between chronic subsyndromal symptoms
of depression (SSD), cerebrospinal fluid (CSF) biomarkers, and neuropsychological
performance in individuals with mild cognitive impairment (MCI). METHODS:
Participants included 238 older adults diagnosed with MCI from the Alzheimer's
Disease Neuroimaging Initiative repository with cognitive and CSF amyloid beta
(Abeta1-42 ), total tau (t-tau), and phosphorylated tau (p-tau) data. The
Neuropsychiatric Inventory identified individuals with chronic endorsement (SSD
group N = 80) or no endorsement (non-SSD group N = 158) of depressive symptoms
across timepoints. CSF biomarker and cognitive performance were evaluated with
linear regression models adjusting for age, education, gender, APOE genotype,
global cognitive status, and SSD group. RESULTS: As compared to the non-SSD
group, the SSD group displayed lower CSF Abeta1-42 levels (beta = -24.293, S.E. =
6.345, P < 0.001). No group differences were observed for CSF t-tau (P = 0.497)
or p-tau levels (P = 0.392). Lower CSF Abeta1-42 levels were associated with
poorer performance on learning (beta = 0.041, S.E. = 0.018, P = 0.021) and memory
(beta = -0.012, S.E. = 0.005, P = 0.031) measures, whereas higher CSF t-tau
levels were associated with poorer performance on measures of global cognition
(beta = 0.022, S.E = 0.008, P = 0.007) and language (beta = -0.010, S.E = 0.004,
P = 0.019). SSD was independently associated with diminished global cognition,
learning and memory, language, and executive function performance over and above
the effects of CSF biomarkers (all P < 0.05). CONCLUSIONS: MCI participants with
SSD displayed diminished CSF Abeta1-42 levels but did not differ from non-SSD
controls in CSF tau levels. Additionally, CSF biomarkers and SSD independently
accounted for variance in cognitive performance, suggesting that these factors
may uniquely confer cognitive risk in MCI.
PMID- 29953669
TI - The effect of pre-phototest sun exposure on minimal erythema dose and minimal
melanogenic dose among skin phototypes III, IV and V.
AB - BACKGROUND: Ethnicity, skin phototype and colour influenced minimal erythema dose
(MED). Sun exposure has been postulated to increase MED. We determined immediate
pigment darkening dose to UVA (IPDDA), MED and minimal melanogenic dose (MMD) for
UVB and UVA, and investigated factors affecting these doses. METHODS: Skin
phototype was determined using Fitzpatrick phototype quiz, DSMII ColorMeter
measured skin colours, sun exposure quantified using an index (SEI) and phototest
performed with MEDlight-Multitester. RESULTS: A total of 167 healthy volunteers
participated. There were 110 (66%) females and 56 (34%) males; 124 (74.7%) were
Malay, 27 (16.3%) Chinese and 14 (8.4%) Indians. One hundred and nine (65.7%)
skin phototype IV, 30 (18.1%) phototype III and 27 (16.3%) phototype V. IPDDA
ranges from 6 +/- 1.5-5.7 +/- 1.4 J/cm2 . MED-UVB were 96.9 +/- 17.6, 124 +/-
29.3 and 118.6 +/- 27.4 mJ/cm2 for phototype III, IV and V, respectively. All MED
UVA were outside the tested dose range of 3.6-11 J/cm2 . MMD-UVB were 106 +/-
18.2, 134 +/- 25.6 and 136 +/- 31.1 mJ/cm2 while MMD-UVA were 4.1 +/- 4.1, 4.9 +/
3.8 and 5.7 +/- 3.7 J/cm2 respectively for phototypes III, IV and V. MED-UVB,
MMD-UVB and MMD-UVA did not depend on skin phototype. Facultative skin whiteness
(L*), erythema (E) and melanin content (M) correlated significantly with MED-UVB
while constitutive skin colours were significant for L*, yellowness (b*), E and
M. Sun exposure did not significantly correlate with MED-UVB and MMDs, however,
an inverse relationship with MED-UVB was demonstrated. CONCLUSION: Minimal
erythema doses in our cohort were slightly different from other regional
countries. Constitutive and facultative skin whiteness, erythema and melanin
content correlated with MED. There was no association between skin phototype and
sun exposure with MED or MMD.
PMID- 29953670
TI - Comparison of Methods for Improving Fracture Risk Assessment in Diabetes: The
Manitoba BMD Registry.
AB - Type 2 diabetes is a risk factor for fracture independent of FRAX (fracture risk
assessment) probability. We directly compared four proposed methods to improve
the performance of FRAX for type 2 diabetes by: (1) including the rheumatoid
arthritis (RA) input to FRAX; (2) making a trabecular bone score (TBS) adjustment
to FRAX; (3) reducing the femoral neck T-score input to FRAX by 0.5 SD; and (4)
increasing the age input to FRAX by 10 years. We examined major osteoporotic
fractures (MOFs) and hip fractures (HFs) over a mean of 8.3 years observation
among 44,543 women and men 40 years of age or older (4136 with diabetes) with
baseline lumbar spine and hip DXA from 1999 through 2016. Controlled for
unadjusted FRAX probability, diabetes was associated with an increased risk for
MOFs and HFs. All four FRAX adjustments attenuated the effect of diabetes, but a
residual effect of diabetes was seen on MOF risk after TBS adjustment, and on HF
risk after the RA and TBS adjustments. Among those with diabetes, unadjusted FRAX
risk underestimated MOF (observed/predicted ratio 1.15; 95% CI, 1.03 to 1.28),
but this was no longer significant after applying the diabetes adjustments. HF
risk was more severely underestimated (observed/predicted ratio 1.85; 95% CI,
1.51 to 2.20) and was only partially corrected with the diabetes adjustments
(still significant for the RA and TBS adjustments). Among those with diabetes,
there was moderate reclassification based upon a fixed MOF cut-off of 20% (4.1%
to 7.1%) or fixed HF cut-off of 3% (5.7% to 16.5%). Net reclassification
improvement increased for MOF with each of the diabetes adjustments (range 3.9%
to 5.6% in the diabetes subgroup). In conclusion, each of the proposed methods
for addressing limitations in the ability of FRAX to assess fracture risk in
individuals with diabetes was found to improve performance, though no single
method was optimal in all settings. (c) 2018 American Society for Bone and
Mineral Research.
PMID- 29953671
TI - The influence of aging on the methylation status of brain-derived neurotrophic
factor gene in blood.
AB - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is involved in the
pathophysiology of psychiatric disorders in adults and elderly individuals, and
as a result, the DNA methylation (DNAm) of the BDNF gene in peripheral tissues
including blood has been extensively examined to develop a useful biomarker for
psychiatric disorders. However, studies to date have not previously investigated
the effect of age on DNAm of the BDNF gene in blood. In this context, we measured
DNAm of 39 CpG units in the CpG island at the promoter of exon I of the BDNF
gene. METHODS: We analyzed genomic DNA from peripheral blood of 105 health
Japanese women 20 to 80 years of age to identify aging-associated change in DNAm
of the BDNF gene. In addition, we examined the relationship between total MMSE
scores, numbers of stressful life events, and serum BDNF levels on DNAm of the
BDNF gene. The DNAm rate at each CpG unit was measured using a MassArray(r)
system (Agena Bioscience), and serum BDNF levels were measured by ELISA. RESULTS:
There was a significant correlation between DNAm and age in 13 CpGs. However,
there was no significant correlation between DNAm and total MMSE scores, numbers
of life events, or serum BDNF levels. CONCLUSION: Despite the small number of
subjects and the inclusion of only female subjects, our results suggest that DNAm
of 13 CpGs of the BDNF gene may be an appropriate biomarker for aging and useful
for predicting increased susceptibility to age-related psychiatric disorders.
PMID- 29953672
TI - Silencing forkhead box M1 promotes apoptosis and autophagy through
SIRT7/mTOR/IGF2 pathway in gastric cancer cells.
AB - Forkhead box M1 (FOXM1) was initially identified as an oncogenic transcription
factor, and multiple lines of evidence have demonstrated that FOXM1 is abundantly
expressed and plays an irreplaceable role in several types of human cancers.
Also, evidence has shown the association of FOXM1 with gastric carcinoma
metastasis and patients prognosis; however, the potential role and molecular
mechanism of FOXM1 in gastric cancer cell apoptosis are still obscure. The
current study indicates that FOXM1 is highly expressed in a variety of gastric
carcinoma cell lines, such as BGC823, MGC803, AGS, and SGC-7901, compared with
the normal gastric mucosal epithelial cell lines CES-1. FOXM1 silence markedly
inhibits AGS and SGC-7901 cell survival and proliferation, increases their
apoptosis, and modulates apoptosis-related protein expression, including reduced
Bcl-2 level and increased Bax and caspase-3 levels. Further study showed that
FOXM1 depletion induced cell autophagy through increasing the level of beclin-1
and decreasing the P62 expression. We next corroborated that FOXM1 silence
abolished the expression of Sirtuin 7 (SIRT7) and increased the level of insulin
like growth factor 2 (IGF2) and mammalian target of rapamycin (mTOR). Finally,
our data documented that the SIRT7/mTOR/IGF2 pathway was involved in the function
of FOXM1 in AGS cell growth and apoptosis. In conclusion, these results confirmed
that FOXM1 is involved in gastric carcinoma progression via the SIRT7/mTOR/IGF2
pathway.
PMID- 29953673
TI - Effects of dietary phytoncides extracted from Korean pine (Pinus koraiensis) cone
on performance, egg quality, gut microflora, and immune response in laying hens.
AB - This study was conducted to evaluate the effects of dietary phytoncides extracted
from discarded Korean pine cones (Pinus koraiensis) on the performance, egg
quality, immune response and gut microflora in laying hens. A total of 400 Hy
Line brown laying hens (50-week old) were allotted into four dietary treatments
including a control diet or a diet supplemented with phytoncides at 0.002%,
0.004% and 0.008%. During the 6 weeks of experimental feeding, 0.008% of dietary
phytoncides improved egg production, feed conversion ratio (p < 0.05), but not
feed intake, egg weight or feed efficiency. Although dietary phytoncides had no
effect on egg quality, decreases in Haugh units depending on storage periods were
improved by 0.008% of dietary phytoncides (p < 0.05). To investigate the roles of
dietary phytoncides on the alteration of the immune response during inflammation,
lipopolysaccharide (LPS) or saline was intraperitoneally injected into 10 hens
per diet group on the end date of the experimental feeding period. Serum
immunoglobulins and splenic cytokine expression at mRNA levels were then measured
at 4 hr postinjection. Although the levels of IgA were decreased by LPS injection
in all dietary groups, dietary phytoncides at 0.008% showed a higher level of IgA
by LPS (p < 0.05). Interestingly, although LPS injection resulted in an enhanced
expression of proinflammatory cytokines such as IL-1beta and IL-6, dietary
phytoncides at 0.008% showed less increased levels of them (p < 0.05). Gut
microflora was examined from 10 hens per diet group at the end of the
experimental period. While the number of Lactobacillus spp. was increased (p <
0.05), Escherichia coli counts in the cecal contents were decreased by 0.008% of
dietary phytoncides. Taken together, these results demonstrate that dietary
supplementation of 0.008% phytoncides improved the egg production, immune
responses during inflammation and gut microflora in laying hens.
PMID- 29953674
TI - Test-retest reliability of clitoral blood flow measurements using color Doppler
ultrasonography at rest and after a pelvic floor contraction task in healthy
adult women.
AB - AIMS: Test-retest reliability assessment of the dorsal clitoral artery's blood
flow at rest and after muscle activation has never been documented. If this
outcome measure is to be used in conditions impeding vascularity, it requires a
psychometric evaluation. The aim of this study was to assess the inter-session
test-retest reliability of clitoral blood flow in healthy women using color
Doppler ultrasonography at rest and after a pelvic floor muscle (PFM) contraction
task. METHODS: Two assessment sessions were conducted using a clinical ultrasound
system. Clitoral blood flow measurements were repeated at rest and after a PFM
contraction task. Measurements of the peak systolic velocity (PSV), time-averaged
maximum velocity (TAMX), end-diastolic velocity (EDV), pulsatility index (PI),
and resistance index (RI) were taken. The test-retest reliability was assessed
using paired t-test, intraclass correlation coefficient (ICC), and Bland-Altman
plots. RESULTS: For reliability at rest, ICC values were 0.95 for PSV, 0.87 for
TAMX, and 0.67 for both PI and RI. The variability between measurements, as per
Bland-Altman plots, was small for PSV, TAMX, and RI and acceptable for PI. For
reliability after the PFM contractions task, ICC values were 0.85 for PSV, 0.77
for TAMX, 0.79 for PI, and 0.81 for RI. The variability between measurements was
small for PSV and RI and acceptable for TAMX and PI. EDV parameter did not
perform as well in both conditions. CONCLUSIONS: Assessment of the clitoral blood
flow with color Doppler ultrasound is reliable at rest and after a PFM
contraction task.
PMID- 29953675
TI - Severe hypocalcaemia-related pustular psoriasis in an 83-year-old woman with
Fahr's syndrome: a case report.
PMID- 29953676
TI - Psoriasis, metabolic syndrome and cardiovascular risk factors. A population-based
study.
AB - BACKGROUND: Psoriasis is a very prevalent systemic chronic inflammatory disease.
Major cardiovascular events are the main cause of mortality in these patients
which suggests an association between psoriasis and traditional cardiovascular
risk factors. OBJECTIVE: To identify classic cardiovascular risk factors and
metabolic syndrome (MS) in patients with psoriasis, their possible association
with its severity and compare it with the non-psoriatic population. METHODS: This
is an observational and cross-sectional population study in Lleida (Spain) from a
joint hospital/primary care database. RESULTS: The database comprised 398 701
individuals. There were 6868 cases registered as psoriasis (1.7%), and 499 of
them (7.3%) were classified as moderate-severe psoriasis. Patients with psoriasis
had a higher prevalence of traditional cardiovascular risk factors than non
psoriatic population: diabetes mellitus 2 (13.9% vs 7.4%, OR 2.01), dyslipidaemia
(28.8% vs 17.4%, OR 1.92), arterial hypertension (31.2% vs 19.0%, OR 1.93),
obesity (33.7% vs 28.1%, OR 1.30), altered fasting basal glycaemia (21.4% vs
15.1%, OR 1.54), low cholesterol HDL (38.1% vs 32.3%, OR 1.29),
hypertriglyceridaemia (45.7% vs 35.2%, OR 1.55) and high waist circumference
(75.7% vs 72.3%, OR 1.19). MS was more prevalent in psoriatic patients (28.3% vs
15.1%, OR 2.21), and cardiovascular risk factors were similar between psoriasis
severity groups. Psoriatic patients had a higher prevalence of ischaemic heart
disease (3.3% vs 1.8%, OR 1.87) and vascular cerebral accidents (1.8% vs 1.2%, OR
1.55). A model for MS showed a significant nonlinear relationship with age and
sex and significant differences between patients with and without psoriasis.
CONCLUSION: We found statistically significant differences in relation to the
prevalence of cardiovascular risk factors, MS and major cardiovascular events in
psoriatic patients. However, differences were not seen between psoriasis severity
groups. Our work reinforces the need for a multidisciplinary approach and close
monitoring of cardiovascular risk factors in these patients to prevent a
cardiovascular event.
PMID- 29953677
TI - Tattooing and psoriasis: dermatologists' knowledge, attitudes and practices. An
international study.
PMID- 29953678
TI - Paradoxical eczematous reaction to ixekizumab.
PMID- 29953679
TI - The role of dermoscopy in the diagnosis of deep mycoses and systemic mycoses with
cutaneous involvement: Comment on 'Dermoscopy in disseminated sporotrichosis'.
PMID- 29953680
TI - Hypoxia-inducible factor controls immunoregulatory properties of myeloid cells in
mouse cardiac allografts - an experimental study.
AB - Hypoxia-inducible factors (HIFs) play a critical role in inflammatory properties
of myeloid-derived cells. The effect of HIFs on myeloid-derived cell functions in
organ transplantation remains unknown, however. We transplanted hearts into
transgenic mice with myeloid cell-targeted deletions of HIF-1alpha or its
negative regulator von Hippel-Lindau (VHL) to investigate the effects of HIF
1alpha inactivation or HIF pathway activation, respectively, on ischemia
reperfusion injury (IRI) and acute rejection. Deletion of VHL in myeloid cells
enhanced mRNA expression of anti-inflammatory genes IDO, Arg-1, and HO-1 in
vitro. In vivo, VHL-/- myeloid-derived cells of allograft recipients alleviated
IRI and acute rejection, evidenced by reduced cardiomyocyte damage, decreased
proinflammatory cytokine mRNA levels, and absence of inflammatory infiltrate at 5
days after transplantation. Ultimately, allograft survival was significantly
prolonged. In vitro, VHL-/- myeloid-derived cells dose-dependently inhibited T
cell proliferation. Myeloid cells with HIF-1alpha-deletion retained
proinflammatory qualities in vitro and in vivo. Deletion of VHL in myeloid cells
of nonimmunosuppressed cardiac allograft recipients reduced myocardial injury and
acute rejection. We suggest that HIF transcription factors induce a regulatory
phenotype in myeloid-derived cells, which may be harnessed as a novel therapeutic
strategy to regulate immune responses after heart transplantation.
PMID- 29953681
TI - Dermatological infections in organ transplant recipients: a retrospective study
on 222 patients.
PMID- 29953682
TI - Pharmacogenetic evaluation of a DISP1 gene variant in antidepressant treatment of
obsessive-compulsive disorder.
AB - OBJECTIVES: A recent genome-wide association study (GWAS) in obsessive-compulsive
disorder (OCD) reported a significant marker in the dispatched homolog 1
(Drosophila) gene (DISP1 gene) associated with serotonin reuptake inhibitor (SRI)
antidepressant response (Qin et al., ). DISP1 has never been examined before in
terms of association with SRI response until this GWAS. We attempt to replicate
the GWAS finding by investigating the association of the DISP1 rs17162912
polymorphism with SRI response in our sample of 112 European Caucasian OCD
patients. METHODS: Patients were previously treated naturalistically with up to 6
different SRIs sequentially, including 5 selective SRIs (fluoxetine, fluvoxamine,
sertraline, paroxetine, and citalopram) and 1 SRI (clomipramine). Each medication
trial was evaluated retrospectively for response and was rated categorically as
either responder or nonresponder using the Clinical Global Impression-Improvement
scale. Fisher's exact test was used to investigate the relationship between the
DISP1 rs17162912 genotype distribution and SRI response. RESULTS: We did not
observe a significant association between rs17162912 and SRI response (p = .32).
CONCLUSION: This replication study did not support the role of DISP1 in
predicting SRI response in OCD; however, methodological differences between the
original GWAS and our study, as well as limited power and low minor allele
frequency, may have hindered replication.
PMID- 29953683
TI - Added-Value Surfactants.
AB - Surfactants are ubiquitous in cellular membranes, detergents or as emulsification
agents. Due to their amphiphilic properties, they cannot only mediate between two
domains of very different solvent compatibility like water and organic but also
show fascinating self-assembly features resulting in micelles, vesicles, or
lyotropic liquid crystals. The current review article highlights some approaches
towards the next generation surfactants, for example, those with catalytically
active heads. Furthermore, it is shown that amphiphilic properties can be
obtained beyond the classical hydrophobic-hydrophilic interplay, for instance
with surfactants containing one molecular block with a special shape. Whereas,
classical surfactants are static, researchers have become more interested in
species that are able to change their properties depending on external triggers.
The article discusses examples for surfactants sensitive to chemical (e.g., pH
value) or physical triggers (temperature, electric and magnetic fields).
PMID- 29953684
TI - Prevalence, predictors and comorbidity of dry skin in the general population.
AB - BACKGROUND: Dry skin is a frequent and multifaceted condition which can be
associated with skin irritation, itch, patient discomfort and manifest skin
disease. In spite of being frequent, little is known about the epidemiology of
dry skin in the population. OBJECTIVE: To determine the prevalence of dry skin in
the German adult population. METHODS: Data of 48 630 employed persons were
assessed on a cross-sectional level in whole-body examinations by experienced
dermatologists during company-based skin screenings conducted in 343 German
companies. Next to the current dermatologic findings, age, gender, allergies,
atopic diseases and the skin type were assessed. RESULTS: In total, n = 14 300
persons (29.4%) were rated as having xerotic skin. Older age but not gender was
associated with xerosis. In the regression analyses controlling for age and
gender, dry skin was a significant predictor for: axillary dermatitis (OR: 4.51;
CI 2.70-7.54), atopic eczema (OR: 3.99; CI 3.42-4.65), exsiccation eczema (OR:
2.96; CI 2.40-3.65), psoriasis (OR: 1.57; CI 1.38-1.78), plantar warts (OR: 1.42;
CI 1.26-1.60), seborrhoeic dermatitis (OR: 1.28; CI 1.16-1.42) and atopic
disposition (OR: 1.17; CI 1.12-1.22). CONCLUSION: Dry skin is a frequent
condition in the adult general population and needs special attention. Known risk
factors may facilitate identifying patients at risk for deterioration.
PMID- 29953685
TI - Meta-analysis and systematic review of population-based epidemiological studies
in idiopathic intracranial hypertension.
AB - Idiopathic intracranial hypertension (IIH) is positively associated with obesity,
mostly in young women. The global increase in obesity may influence the burden of
IIH. Using the PubMed, Embase, MEDLINE and Web of Science databases, a meta
analysis and systematic review of epidemiological studies of IIH were performed
up to June 2017. Temporal changes in IIH incidence were measured, and incidence
rates of IIH were correlated with country-specific World Health Organization
obesity rates. Prevalence data and shunting rates of IIH were recorded. The
quality of epidemiological studies was assessed using the Standards of Reporting
of Neurological Disorders (STROND) criteria. In 15 identified studies, there were
889 patients (87% women), mean age 29.8 years. The incidence of IIH ranged from
0.03 to 2.36 per 100 000 per year. The pooled incidence of IIH was 1.20 per 100
000 per year although there was very high heterogeneity (I2 98%). The incidence
rates of IIH were correlated with country-specific prevalence of obesity
(Spearman's correlation 0.82, P < 0.01). The prevalence of IIH was rarely
recorded. A shunting procedure was reported in 8% of patients. STROND criteria
were variably reported, median of 26.5 of 43 (range 16-35). IIH is a public
health concern as increased obesity prevalence is associated with increased
incidence of IIH. A better quality of epidemiological studies is required to
improve understanding of IIH and inform health policy for IIH management.
PMID- 29953686
TI - Inconsistencies in the assumptions linking punitive sanctions and use of cannabis
and new psychoactive substances in Europe.
PMID- 29953687
TI - Bone morphogenetic protein-2 is a stronger inducer of osteogenesis within muscle
tissue than heterodimeric bone morphogenetic protein-2/6 and -2/7: Implications
for expedited gene-enhanced bone repair.
AB - BACKGROUND: Bone morphogenetic protein (BMP)-2 gene-activated muscle tissue
fragments can regenerate large bone defects in preclinical animal models. The use
of tissue fragments instead of isolated cells expedites gene-enhanced tissue
engineering and may increase the possibility of clinical translation. The present
in vitro study investigated whether the osteoinductive effect of BMP-2 on muscle
tissue fragments can be enhanced using the heterodimers BMP-2/6 or BMP-2/7.
METHODS: Skeletal muscle tissue fragments from rats were cultured in vitro for up
to 20 days in normal medium, osteogenic medium or osteogenic medium supplemented
with either a low (50 ng/ml) or high (200 ng/ml) concentration of recombinant
human BMP-2, BMP-2/6 or BMP-2/7. Osteoinduction was evaluated by a quantitative
reverse transcriptase-polymerase chain reaction, Alizarin red S staining,
immunohistology and histomorphometry. RESULTS: Interestingly, BMP-2 was a
significantly stronger inducer of osteogenic differentiation within muscle tissue
than both heterodimers. Even the low concentration of BMP-2 elicited
significantly higher levels of calcium deposition, bone-specific gene expression
and protein production than the high concentration of both heterodimers. At the
high concentration, BMP-2/7 had a significantly stronger osteogenic effect on
muscle than BMP-2/6. CONCLUSIONS: The homodimer BMP-2 induced osteoblastogenesis
in muscle faster, at a lower concentration and with a higher potency than the
heterodimers BMP-2/6 or BMP-2/7. The findings of this in vitro study encourage
bone repair by muscle implants in combination with BMP-2 single growth factor
delivery, which might be beneficial with respect to clinical translation.
PMID- 29953688
TI - Wild tomato endosperm transcriptomes reveal common roles of genomic imprinting in
both nuclear and cellular endosperm.
AB - Genomic imprinting is a conspicuous feature of the endosperm, a triploid tissue
nurturing the embryo and synchronizing angiosperm seed development. An unknown
subset of imprinted genes (IGs) is critical for successful seed development and
should have highly conserved functions. Recent genome-wide studies have found
limited conservation of IGs among distantly related species, but there is a
paucity of data from closely related lineages. Moreover, most studies focused on
model plants with nuclear endosperm development, and comparisons with properties
of IGs in cellular-type endosperm development are lacking. Using laser-assisted
microdissection, we characterized parent-specific expression in the cellular
endosperm of three wild tomato lineages (Solanum section Lycopersicon). We
identified 1025 candidate IGs and 167 with putative homologs previously
identified as imprinted in distantly related taxa with nuclear-type endosperm.
Forty-two maternally expressed genes (MEGs) and 17 paternally expressed genes
(PEGs) exhibited conserved imprinting status across all three lineages, but
differences in power to assess imprinted expression imply that the actual degree
of conservation might be higher than that directly estimated (20.7% for PEGs and
10.4% for MEGs). Regardless, the level of shared imprinting status was higher for
PEGs than for MEGs, indicating dissimilar evolutionary trajectories. Expression
level data suggest distinct epigenetic modulation of MEGs and PEGs, and gene
ontology analyses revealed MEGs and PEGs to be enriched for different functions.
Importantly, our data provide evidence that MEGs and PEGs interact in modulating
both gene expression and the endosperm cell cycle, and uncovered conserved
cellular functions of IGs uniting taxa with cellular- and nuclear-type endosperm.
PMID- 29953689
TI - Visual hallucinations in dementia and Parkinson's disease: A qualitative
exploration of patient and caregiver experiences.
AB - OBJECTIVES: Visual hallucinations (VHs) can occur in several clinical conditions,
of which the dementias, broadly defined, and Parkinson's disease rank among the
most common. There is limited research on the lived experience of hallucinations
among affected individuals and therefore a lack of evidence-based management
strategies. This study used qualitative methods to explore the VH experience of
individuals with dementia or Parkinson's disease and their informal caregivers.
METHODS: In-depth interviews were conducted with 10 individuals with VHs and
dementia and 11 informal caregivers, and 11 individuals with VHs and Parkinson's
disease and 9 informal caregivers. Interviews were analysed using an inductive
thematic approach. RESULTS: Three themes emerged from the data: "Insight and
distress," "Caregiver approach: challenging v reassurance," and "Normality and
stigma." Insight appeared to affect whether hallucinations were perceived as
threatening and whether acceptance occurred over time. Emotional reactions and
management strategies varied as insight changed with disease progression.
Concerns around stigmatisation negatively influenced help-seeking and acceptance
of the hallucinations. CONCLUSIONS: Degree of insight and cognitive ability
appear fundamental to the lived experience of hallucinations. Irrespective of the
clinical context, support in early stages should focus on raising awareness of
VH, symptom disclosure, stigma reduction, and contact with others affected. In
later stages, the focus shifts to informal caregiver needs and a flexible
approach to reassuring those affected.
PMID- 29953690
TI - The lifestyle behaviours of young adults with intellectual disabilities as they
transition from school to adulthood: A pilot and feasibility study.
AB - BACKGROUND: In the general population, the transition from adolescence to
adulthood has been identified as a "high-risk" period for weight gain. There has
been no research examining health behaviours over this transition in adults with
intellectual disabilities. METHODS/DESIGN: The feasibility of recruitment,
retention and relevant health behaviours were measured in 31 adolescents with
mild-moderate intellectual disabilities. Anthropometric, objective physical
activity, dietary and self-determination measures were collected over a 12-month
transitional period from school to adulthood. RESULTS: Key results suggest weight
and BMI increased significantly from month 6 to month 12 (p = 0.044 and p =
0.043). Waist circumference increased significantly from baseline to month 12 (p
= 0.049), and from month 6 to month 12 (p = 0.03). DISCUSSION: Recruiting and
retaining young adults with intellectual disabilities over a 12-month health
behaviour study is feasible. The data indicate the transition from school to
adulthood may be the start of a high-risk period for weight gain.
PMID- 29953691
TI - Dermoscopy in disseminated sporotrichosis.
PMID- 29953692
TI - Instagrowth: A Longitudinal Growth Mixture Model of Social Media Time Use Across
Adolescence.
AB - This study examined differential patterns of time spent using social media in a
sample of 457 adolescents over a 6-year period. The majority of adolescents
(83%), termed moderate users, reported steady social media use over time. A
second group (increasers: 12%) reported low social media use that increased
gradually and ended high at the end of the study. A third group, called peak
users (6%), reported low social media that increased quickly after a few years
and then returned to baseline levels. Low self-regulation predicted being an
increaser or peak user. Being a moderate user tended to be related to lower
levels of depression, aggression, delinquency, social media problems, and
cyberbullying across time, as compared with the other groups.
PMID- 29953693
TI - Inhibitory effects of deoxynivalenol on pathogenesis of Candida albicans.
AB - AIMS: To probe the inhibitory effects of deoxynivalenol (DON) on growth and
biofilms of yeast and bacterial pathogens. METHODS AND RESULTS: Crystal violet
quantification, XTT reduction assay, confocal and scanning electron microscopic
imaging, and yeast-to-hyphal inhibition assays were performed to demonstrate the
inhibitory effects of DON. Our results show that DON and its modified form (3
acetyl-DON) caused dose-dependent inhibition of Candida albicans pathogenesis
under in vitro conditions. DON significantly reduced C. albicans biofilm
formation and metabolic activities, disrupted preformed biofilms without
affecting planktonic cell growth, and inhibited hyphal protrusions in embedded
colonies and free-living planktonic cells. We also show that DON and its
derivatives function by interacting with lanosterol 14alpha-demethylase, thus
mimicking the action mechanism of azole drugs. CONCLUSIONS: Highlighting the
importance of C. albicans biofilms and hyphal filamentations in inducing pathogen
vigour, this study demonstrates the antihyphal and antibiofilm potential of DON
against C. albicans. SIGNIFICANCE AND IMPACT OF THE STUDY: Mycotoxin-producing
moulds are able to dominate and control other microbes and insects in ecological
niches. At times, they are known to eradicate biofilms of their intruders or
symbiotic partners. In view of this coincident notion, the study proposes a role
for mycotoxins as a biofilm inhibitor in ecological niches.
PMID- 29953694
TI - Clinical Predictors of Acute Brain Injury in Carbon Monoxide Poisoning Patients
With Altered Mental Status at Admission to Emergency Department.
AB - OBJECTIVES: Objective screening tool for patients at a high risk of developing
acute brain injury (ABI) is necessary for the proper treatment of carbon monoxide
(CO) poisoning patients. The aim of this study is to identify clinical factors
that could predict ABI due to CO poisoning in patients with an altered mental
status. METHODS: A prospectively collected CO poisoning registry at a single
academic medical center was retrospectively analyzed. CO poisoning patients with
an altered mental status at the emergency department, defined as unalert on the
alert/responsive to voice/responsive to pain/unresponsive scale and underwent
diffusion-weighted magnetic resonance imaging (DW-MRI) between January 1, 2013,
and December 31, 2015, were included. ABI was defined as the presence of acute
hypoxic brain lesions. Clinical predictors of ABI were identified by multivariate
logistic regression analysis. RESULTS: Of 180 patients, 67 (37.2%) had ABI as
revealed by DW-MRI. Multivariate analysis showed that CO exposure duration > 5
hours (adjusted odds ratio [AOR] = 7.082; 95% confidence interval [CI] = 3.463
15.014; p < 0.001) defined as the time between CO exposure and rescue, abnormal
white blood cell count (AOR = 2.568, 95% CI = 1.188-5.700, p = 0.02), and
abnormal creatinine concentration (AOR = 2.667, 95% CI = 1.110-6.605, p = 0.03)
were predictors of ABI. CO exposure duration had the highest predictive value
(area under the curve, 0.815), and the optimal cutoff value was 5 hours.
Moreover, increasing exposure durations (quartile) indicated a stepwise increase
in the risk of ABI. CONCLUSIONS: In CO poisoning patients with an altered mental
status, CO exposure duration was useful for predicting ABI, which may help
clinicians or paramedics identify high-risk patients and provide treatment on
priority.
PMID- 29953695
TI - Engaging with and navigating limbo: Lived experiences of siblings of adults with
autism spectrum disorders.
AB - BACKGROUND: Supporting an adult with autism spectrum disorder (ASD) can be
associated with family stress but also with personal growth and resilience.
Research providing insight into how typically developing siblings make sense of
their unique sibling relationships in adulthood remains limited. METHOD: Using
interpretative phenomenological analysis, this study explored subjective
experiences of eight siblings of adults with ASD and co-occurring intellectual
disability. RESULTS: Analysis of interview transcripts revealed a complex lived
experience explained by the overarching theme "engaging with and navigating
limbo", which was characterized by commitment to the sibling relationship, power
tensions in the family, uncertainty about the future and negotiating the tension
between relational closeness and distance. CONCLUSION: Using family systems
theory, overregulation and closed communication emerged as processes relevant to
families living with ASD. Clinical opportunities to support family communication,
change tolerance and belonging are discussed.
PMID- 29953697
TI - Clinical Snippets.
PMID- 29953696
TI - Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and
meta-analysis.
AB - BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is the most feared
complication in patients treated with oral anticoagulants due to non-valvular
atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of
ICH compared with vitamin K antagonists (VKAs). We performed a systematic review
and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with
VKA-related ICH. METHODS: We calculated the corresponding risk ratios (RRs) in
each included study to express the relative risk of fatal ICH amongst all
patients receiving oral anticoagulation with either NOACs or VKAs. We
additionally evaluated the mortality rates in NOAC-related ICH in patients
treated with and without NOAC-specific reversal agents (idarucizumab and factor
Xa inhibitors antidote). Case fatality was evaluated at 30-90 days following
symptom onset. RESULTS: Our literature search identified six eligible studies
(four randomized controlled trials and two open-label trials of NOAC-specific
reversal agents). In pairwise analyses, NOACs were found to have a lower risk of
fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36-0.58]
with no heterogeneity (I2 = 0%) across included randomized controlled trials.
However, the case fatality rate was similar in NOAC-related and VKA-related (RR,
1.00; 95% CI, 0.84-1.19) ICH with no evidence of heterogeneity (I2 = 0%). In the
indirect analysis, the case fatality rate of NOAC-related ICH in patients treated
with specific reversal agents was lower compared with the remainder of the
patients [17% (95% CI, 11-24%) vs. 41% (95% CI, 34-49%); P < 0.001]. CONCLUSIONS:
Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with
non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons
indicate that NOAC-specific reversal agents may be associated with a lower case
fatality rate in NOAC-related ICH.
PMID- 29953698
TI - 45th meeting of the Arbeitsgemeinschaft Dermatologische Forschung.
PMID- 29953699
TI - Tremor in motor neuron disease may be central rather than peripheral in origin.
AB - BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of
degenerative diseases affecting motor neurons. Recent clinical and post-mortem
observations have revealed considerable variability in the phenotype. Rhythmic
involuntary oscillations of the hands during action, resembling tremor, can occur
in MND, but their pathophysiology has not yet been investigated. METHODS: A total
of 120 consecutive patients with MND were screened for tremor. Twelve patients
with action tremor and no other movement disorders were found. Ten took part in
the study. Tremor was recorded bilaterally using surface electromyography (EMG)
and triaxial accelerometer, with and without a variable weight load. Power
spectra of rectified EMG and accelerometric signal were calculated. To
investigate a possible cerebellar involvement, eyeblink classic conditioning was
performed in five patients. RESULTS: Action tremor was present in about 10% of
our population. All patients showed distal postural tremor of low amplitude and
constant frequency, bilateral with a small degree of asymmetry. Two also showed
simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging
from 4 to 12 Hz was found in all patients. Loading did not change peak frequency
in either the electromyographic or accelerometric power spectra. Compared with
healthy volunteers, patients had a smaller number of conditioned responses during
eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with
MND can present with action tremor of a central origin, possibly due to a
cerebellar dysfunction. This evidence supports the novel idea of MND as a
multisystem neurodegenerative disease and that action tremor can be part of this
condition.
PMID- 29953700
TI - Violent incidents in a secure service for individuals with learning disabilities:
Incident types, circumstances and staff responses.
AB - BACKGROUND: The issue of violence in secure services has long been recognized
both in the UK and worldwide. However, there is currently scarce literature
available about violence within learning disability (LD) secure settings.
METHODS: Secondary data analysis was conducted on violent incidents, using
information routinely collected by the staff over a 1-year period. RESULTS:
Physical assaults were the most frequent type of incident, and the distribution
in terms of days or months was homogenous and incidents were concentrated in the
corridors, lounges and dining rooms of secure facilities. Antipsychotic
medication was not regularly prescribed. Generalized linear modelling analyses
revealed significant predictors that increased the chances of seclusion and
physical restraint, such as being female or directing the violence towards staff.
CONCLUSIONS: These findings can inform staff training on violence prevention and
suggest that increased ward-based supervision and enhanced use of psychological
formulations may help in reducing violence within this service context.
PMID- 29953701
TI - Differential leukocyte counts on admission predict outcomes in patients with
acute ischaemic stroke treated with intravenous thrombolysis.
AB - BACKGROUND AND PURPOSE: To determine the association of differential leukocyte
counts on admission with efficacy and safety outcomes in patients with acute
ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). METHODS:
Consecutive patients with AIS receiving IVT were evaluated at two stroke centers.
Differential leukocyte counts and neutrophil:lymphocyte ratio (NLR) were
determined during the initial 12 h of admission. Efficacy outcomes were favorable
functional outcome (FFO) (modified Rankin Scale scores of 0-1) and functional
independence (FI) (modified Rankin Scale scores of 0-2) at 3 months, whereas
safety outcomes were symptomatic intracranial hemorrhage and 3-month mortality.
RESULTS: Among 657 IVT-treated patients with AIS, the mean age was 64 +/- 14
years, 50% were female and median National Institutes of Health Stroke Scale
score was 7 points (interquartile range, 4-13). Lower neutrophil and leukocyte
counts and NLR counts were observed in patients with 3-month FFO and FI, whereas
higher counts were observed in patients who died at 3 months. The best
discriminative factors for 3-month FFO and FI were NLR < 2.2 (sensitivity 51.4%,
specificity 63.1%) and leukocyte count <8100/MUL (sensitivity 57.5%, specificity
55.1%), respectively. After adjustment for potential confounders, NLR < 2.2 was
associated with higher odds of FFO [odds ratio (OR), 1.56; 95% confidence
interval (CI), 1.08-2.24; P = 0.018], whereas leukocyte count <8100/MUL
demonstrated higher odds of 3-month FI (OR, 1.69; 95% CI, 1.11-2.57; P = 0.014)
and lower odds of 3-month mortality (OR, 0.31; 95% CI, 0.16-0.60; P = 0.001).
Combined neutrophil (<6800/MUL) and leukocyte (<8100/MUL) counts demonstrated a
strong interaction for 3-month FI (OR, 1.73; 95% CI, 1.13-2.67; P interaction =
0.012). CONCLUSIONS: Differential leukocyte counts on admission were
independently associated with clinical outcomes in patients with AIS treated with
IVT. These inflammatory biomarkers are potential targets for adjunctive
neuroprotection in this stroke subgroup.
PMID- 29953702
TI - Night noise exposure and risk of death by suicide in adults living in
metropolitan areas.
AB - BACKGROUND: Noise is defined as "sound that is unwanted, unpleasant, or harmful
to health." It may induce negative emotions and mental health problems and even
may leads to increased suicide risk. Little attention has been paid so far to a
potential link between noise and suicide. We investigated the association between
nighttime environmental noise and suicide death in adults in the Republic of
Korea. METHODS: We analyzed the data from the National Health Insurance Service
National Sample Cohort, with a 4-year baseline (2002-2005) and an 8-year follow
up (2006-2013) assessment. A total of 155,492 adults constituted the study
sample: younger adults (20-54 years, n = 124,994), or older adults (>=55 years, n
= 30,498), and adults with mood and anxiety disorders (n = 34,615). Suicide death
was defined as per International Classification of Diseases-10 code X60-X84. Data
on nighttime noise were obtained from the National Noise Information System.
RESULTS: During the study period, 315 (0.2%) died of suicide. The incidence of
suicide per 100,000 person-years was 25.71. With interquartile range increases in
nighttime noise, the adjusted hazard ratio (HR) for suicide death was
significantly increased: 1.32 (95% confidence interval [CI]: 1.02-1.70) for
younger adults, 1.43 (95% CI: 1.01-2.02) for older adults, and 1.55 (95% CI: 1.10
2.19) for adults with mental illness. In the penalized regression spline models,
the HRs for suicide death were gradually increased with environmental noise
levels, and the risk was the highest for adults with mental illness. CONCLUSIONS:
We found a significant association between exposure to nighttime noise and the
risk of suicide death in adults in the Republic of Korea.
PMID- 29953703
TI - The Identity of "Ternary" A/Tl/Pb or K/Tl/Bi Solid Mixtures and Binary Zintl
Anions Isolated From Their Solutions.
AB - Investigations of solid mixtures of the elemental combinations A/Tl/Pb (A=Na, K)
and K/Tl/Bi indicate the presence of multiple binary and ternary Zintl phases,
among them new ones containing Tl and Pb or Bi, respectively. Extractions with
en/crypt-222 afford single crystals of several novel binary anions, including
[Tl@Tl4 Pb8 ]4- and (Tl4 Bi3 )3- . [Tl@Tl4 Pb8 ]4- adopts a closo-type cage
structure despite possessing one additional electron; it is therefore
isostructural, yet not isoelectronic, with homoatomic [Tl@Tl12 ]11- obtained by
solid state reactions. (Tl4 Bi3 )3- is a rare case of a pentagonal bipyramidal
Zintl anion, yet the first binary one, and (unlike Tl77- ) the first one with a
proper closo-type electron count. Assignment of the numbers and positions of the
Tl/Pb or Tl/Bi atoms within the anionic clusters, indistinguishable in classical
X-ray diffraction experiments, was achieved by means of quantum chemistry. The
studies shed light on the complex situation in solid heavy element mixtures and
their substantial differences from the composition of the Zintl anions obtained
from them by extraction.
PMID- 29953704
TI - A Stable Crown Ether Complex with a Noble-Gas Compound.
AB - Crown ethers have been known for over 50 years, but no example of a complex
between a noble-gas compound and a crown ether or another polydentate ligand had
previously been reported. Xenon trioxide is shown to react with 15-crown-5 to
form the kinetically stable (CH2 CH2 O)5 XeO3 adduct, which, in marked contrast
with solid XeO3 , does not detonate when mechanically shocked. The crystal
structure shows that the five oxygen atoms of the crown ether are coordinated to
the xenon atom of XeO3 . The gas-phase Wiberg bond valences and indices and the
empirical bond valences indicate that the Xe- - -Ocrown bonds are predominantly
electrostatic and are consistent with sigma-hole bonding. Mappings of the
electrostatic potential (EP) onto the Hirshfeld surfaces of XeO3 and 15-crown-5
in (CH2 CH2 O)5 XeO3 and a detailed examination of the molecular electrostatic
potential surface (MEPS) of XeO3 and (CH2 CH2 O)5 reveal regions of negative EP
on the oxygen atoms of (CH2 CH2 O)5 and regions of high positive EP on the xenon
atom, which are also in accordance with sigma-hole interactions.
PMID- 29953705
TI - Low-saturated-fat and low-cholesterol diet does not alter pubertal development
and hormonal status in adolescents.
AB - AIM: The aim was to assess the influence of dietary counselling on the pubertal
development and hormonal status in healthy adolescents. METHODS: We used a
subcohort of 193 healthy boys (52%) and girls (48%) from the Special Turku
Coronary Risk Factor Intervention Project. Participants were recruited by nurses
at the well-baby clinics in Turku Finland in 1990-1992 and randomised into
intervention and control groups. Intervention children received low-saturated fat
and low-cholesterol dietary counselling initiated at seven months of age.
Participants were examined once a year with Tanner staging, anthropometric
measurements and serial reproductive hormones from 10 to 19 years of age. In
girls, postmenarcheal hormones were not analysed. RESULTS: Pubertal hormones in
boys or girls did not differ between the intervention and control groups.
However, we observed slight differences in pubertal progression by Tanner staging
and in anthropometric parameters. The intervention boys progressed faster to G4
(p = 0.008), G5 (p = 0.008) and P5 (p = 0.03). The intervention boys were taller
than control boys (p = 0.04), while weight and body mass index did not differ.
CONCLUSION: Dietary intervention did not affect pubertal hormonal status. This
finding supports the safety of implemented counselling in respect to puberty.
PMID- 29953707
TI - Transition-Metal-Mediated and -Catalyzed C-F Bond Activation by Fluorine
Elimination.
AB - The activation of carbon-fluorine (C-F) bonds is an important topic in synthetic
organic chemistry. Metal-mediated and -catalyzed elimination of beta- or alpha
fluorine proceeds under milder conditions than oxidative addition to C-F bonds.
The beta- or alpha-fluorine elimination is initiated from organometallic
intermediates having fluorine substituents on carbon atoms beta or alpha to metal
centers, respectively. Transformations through these elimination processes (C-F
bond cleavage), which are typically preceded by carbon-carbon (or carbon
heteroatom) bond formation, have been increasingly developed in the past five
years as C-F bond activation methods. In this Minireview, we summarize the
applications of transition-metal-mediated and -catalyzed fluorine elimination to
synthetic organic chemistry from a historical perspective with early studies and
from a systematic perspective with recent studies.
PMID- 29953706
TI - A Two-Dimensional Hole-Transporting Material for High-Performance Perovskite
Solar Cells with 20 % Average Efficiency.
AB - A readily available small molecular hole-transporting material (HTM), OMe-TATPyr,
was synthesized and tested in perovskite solar cells (PSCs). OMe-TATPyr is a two
dimensional pi-conjugated molecule with a pyrene core and four phenyl-thiophene
bridged triarylamine groups. It can be readily synthesized in gram scale with a
low lab cost of around US$ 50 g-1 . The incorporation of the phenyl-thiophene
units in OMe-TATPyr are beneficial for not only carrier transportation through
improved charge delocalization and intermolecular stacking, but also potential
trap passivation via Pb-S interaction as supported by depth-profiling XPS,
photoluminescence, and electrochemical impedance analysis. As a result, an
impressive best power conversion efficiency (PCE) of up to 20.6 % and an average
PCE of 20.0 % with good stability has been achieved for mixed-cation PSCs with
OMe-TATPyr with an area of 0.09 cm2 . A device with an area of 1.08 cm2 based on
OMe-TATPyr demonstrates a PCE of 17.3 %.
PMID- 29953708
TI - Dissecting the basis of novel trait evolution in a radiation with widespread
phylogenetic discordance.
AB - Phylogenetic analyses of trait evolution can provide insight into the
evolutionary processes that initiate and drive phenotypic diversification.
However, recent phylogenomic studies have revealed extensive gene tree-species
tree discordance, which can lead to incorrect inferences of trait evolution if
only a single species tree is used for analysis. This phenomenon-dubbed
"hemiplasy"-is particularly important to consider during analyses of character
evolution in rapidly radiating groups, where discordance is widespread. Here, we
generate whole-transcriptome data for a phylogenetic analysis of 14 species in
the plant genus Jaltomata (the sister clade to Solanum), which has experienced
rapid, recent trait evolution, including in fruit and nectar colour, and flower
size and shape. Consistent with other radiations, we find evidence for rampant
gene tree discordance due to incomplete lineage sorting (ILS) and to
introgression events among the well-supported subclades. As both ILS and
introgression increase the probability of hemiplasy, we perform several analyses
that take discordance into account while identifying genes that might contribute
to phenotypic evolution. Despite discordance, the history of fruit colour
evolution in Jaltomata can be inferred with high confidence, and we find evidence
of de novo adaptive evolution at individual genes associated with fruit colour
variation. In contrast, hemiplasy appears to strongly affect inferences about
floral character transitions in Jaltomata, and we identify candidate loci that
could arise either from multiple lineage-specific substitutions or standing
ancestral polymorphisms. Our analysis provides a generalizable example of how to
manage discordance when identifying loci associated with trait evolution in a
radiating lineage.
PMID- 29953709
TI - Single-Step Construction of the anti-Deoxypropionate Motif from Propylene: Formal
Total Synthesis of the Cuticular Hydrocarbons Isolated from Antitrogus parvulus.
AB - Reported herein is the single-step construction of an anti-configured
deoxypropionate motif by syndiospecific propylene oligomerization catalyzed by a
Cs -symmetric zirconocene complex. After oligomerization, oxidation of the
oligomers by oxygen afforded oligopropylene alcohols in a single step. This
strategy was applied to the single-step preparation of rel-(2R,4S,6R,8S)-2,4,6,8
tetramethylundecan-1-ol, the racemic mixture of the synthetic fragment of the
cuticular hydrocarbons isolated from the cane beetle Antitrogus parvulus.
PMID- 29953710
TI - Extra-Framework Aluminum-Assisted Initial C-C Bond Formation in Methanol-to
Olefins Conversion on Zeolite H-ZSM-5.
AB - Surface methoxy species bound to an extra-framework Al (SMS-EFAL) was
unambiguously identified by advanced 13 C-{27 Al} double-resonance solid-state
NMR technique in the methanol-to-olefins reaction on H-ZSM-5 zeolite. The high
reactivity of the SMS-EFAL leads to the formation of surface ethoxy species and
ethanol as the key intermediates for ethene generation in the early reaction
stage. A direct route for the initial C-C bond formation in ethene was proposed
and corroborated by density functional theory calculations.
PMID- 29953711
TI - In Vivo Incorporation of Azide Groups into DNA by Using Membrane-Permeable
Nucleotide Triesters.
AB - Metabolic incorporation of bioorthogonal functional groups into cellular nucleic
acids can be impeded by insufficient phosphorylation of nucleosides. Previous
studies found that 5azidomethyl-2'-deoxyuridine (AmdU) was incorporated into the
DNA of HeLa cells expressing a low-fidelity thymidine kinase, but not by wild
type HeLa cells. Here we report that membrane-permeable phosphotriester
derivatives of AmdU can exhibit enhanced incorporation into the DNA of wild-type
cells and animals. AmdU monophosphate derivatives bearing either 5'
bispivaloyloxymethyl (POM), 5'-bis-(4-acetoxybenzyl) (AB), or "Protide"
protective groups were used to mask the phosphate group of AmdU prior to its
entry into cells. The POM derivative "POM-AmdU" exhibited better chemical
stability, greater metabolic incorporation efficiency, and lower toxicity than
"AB-AmdU". Remarkably, the addition of POM-AmdU to the water of zebrafish larvae
enabled the biosynthesis of azide-modified DNA throughout the body.
PMID- 29953712
TI - Exploiting the Synthetic Potential of Sesquiterpene Cyclases for Generating
Unnatural Terpenoids.
AB - The substrate flexibility of eight purified sesquiterpene cyclases was evaluated
using six new heteroatom-modified farnesyl pyrophosphates, and the formation of
six new heteroatom-modified macrocyclic and tricyclic sesquiterpenoids is
described. GC-O analysis revealed that tricyclic tetrahydrofuran exhibits an
ethereal, peppery, and camphor-like olfactoric scent.
PMID- 29953713
TI - Liver stiffness reduction and serum fibrosis score improvement in HIV/hepatitis C
virus-coinfected patients treated with direct-acting antivirals.
AB - OBJECTIVES: Only a few studies have addressed liver stiffness dynamics after
hepatitis C virus (HCV) treatment in patients with HIV/HCV coinfection. The aim
was to evaluate the variation in liver stiffness and in serum liver fibrosis
scores in HIV/HCV-coinfected patients before and after treatment with direct
acting antivirals (DAAs). METHODS: Liver stiffness measured using transient
elastography as well as serum liver fibrosis scores [fibrosis-4 (FIB-4) score and
the aspartate aminotransferase to platelet ratio index (APRI)] were evaluated
before and at 6-12 months after DAA treatment. Variation in the outcome variables
was evaluated using the Wilcoxon nonparametric test. Univariate analysis and
multivariate regression models were used. RESULTS: A total of 78 HIV/HCV
coinfected subjects were included in the study. Median values of hepatic
stiffness significantly decreased after DAA treatment compared with baseline
[16.8 (interquartile range (IQR) 10.2-27.0) kPa at baseline vs. 9.4 (IQR 6.7
15.0) kPa after DAA treatment; P < 0.01). Further, a decrease in median FIB-4
score [2.8 (IQR 1.5-4.8) vs. 2.0 (IQR 1.3-3.2), respectively; P < 0.01] and APRI
[0.9 (IQR 0.5-2.2) vs. 0.4 (IQR 0.2-0.7), respectively; P < 0.01] was found. In
univariate analysis, liver stiffness decrease was associated with increasing age,
'other' HCV genotype (vs. G1), the presence of cirrhosis, higher pre-DAA liver
stiffness, sofosbuvir-based regimens and longer DAA treatment (all P < 0.05).
Multivariate regression confirmed the significance of the association only with
higher baseline liver stiffness (P < 0.01). Greater FIB-4 and APRI reductions
were associated with higher respective baseline values, while the presence of
hepatic steatosis correlated with lower score reduction after DAA. CONCLUSIONS: A
reduction in liver stiffness and an improvement in fibrosis scores were observed
in HIV/HCV-coinfected patients soon after DAA treatment. The clinical
implications of these observations need to be evaluated in larger populations
with longer follow-up.
PMID- 29953714
TI - Auras as a prognostic factor in anterior temporal lobe resections for mesial
temporal sclerosis.
AB - BACKGROUND AND PURPOSE: Anterior temporal lobectomy for mesial temporal sclerosis
(MTS) is a very effective measure for the control of seizures, and the
probability of becoming seizure-free is approximately 70-90%. However, 30% of
patients still experience seizures after surgery. An aura is a subjective ictal
phenomenon that may precede an observable seizure. However, there are few studies
on the prognostic factor aura although, being the initial symptoms of epileptic
seizures, many types of auras have significant localizing or lateralizing value.
This study hypothesized that the type of pre-operative aura may predict the post
surgical outcome in patients with medically refractory temporal lobe epilepsy due
to MTS. METHODS: Of 1214 patients evaluated for surgery in the Epilepsy Center of
Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), a tertiary Brazilian
epilepsy center, 400 underwent anterior temporal lobectomy (ATL) for MTS. The
number and type of auras were analyzed and compared with the Engel classification
for outcome. RESULTS: Analyzing the patients by the type of aura, those who had
extratemporal auras had the worst post-surgical result according to the Engel
classification. Although mesial auras are apparently a good prognostic factor,
patients without aura also had a worse prognosis. There were no differences
between simple and multiple auras. To identify the most appropriate candidates
for ATL, it is very important to consider the favorable prognostic factors for
counseling patients in daily practice. CONCLUSIONS: Patients with symptoms and
clinical signs that suggest extratemporal involvement may have unfavorable
outcomes.
PMID- 29953715
TI - Nuclear nonmetastatic protein 23-H1 expression and epithelial-mesenchymal
transition in laryngeal carcinoma: A pilot investigation.
AB - BACKGROUND: In epithelial-to-mesenchymal transition, epithelial cells lose their
features, acquiring a mesenchymal-like phenotype. Nm23-H1 protein relates to
tumor cells' metastatic potential, its low expression in carcinomas often meaning
a poor prognosis. This study newly investigated the role of nuclear nm23-H1 in
laryngeal squamous cell carcinoma epithelial-to-mesenchymal transition. METHODS:
Immunohistochemical analyses of nuclear nm23-H1, E-cadherin, N-cadherin, Snail,
Zinc finger E-box binding homeobox (ZEB)1, and ZEB2 were performed in 33
consecutive patients with laryngeal SCC. RESULTS: Mean nuclear nm23-H1 expression
was lower in patients whose disease recurred (P = .0046). Disease-free survival
(DFS) was longer for patients whose nuclear nm23-H1 expression was >=10% (P =
.0083). Nuclear nm23-H1 and E-cadherin expressions correlated directly (P =
.018). Mean E-cadherin expression was lower in patients whose disease recurred (P
= .03). The DFS was shorter in patients with ZEB2 expression >=5% (P = .006).
CONCLUSIONS: Nuclear nm23-H1 expression warrants further investigation in
laryngeal SCC as a prognostic marker identifying patients at higher risk of
recurrence. nm23-H1 targeted treatments may be capable of regulating epithelial
to-mesenchymal transition.
PMID- 29953716
TI - Fibrinolysis: strategies to enhance the treatment of acute ischemic stroke.
AB - Stroke is a major cause of disability worldwide, and is the second leading cause
of death after ischemic heart disease. Until recently, tissue-type plasminogen
activator (t-PA) was the only treatment for acute ischemic stroke. If
administered within 4.5 h of symptom onset, t-PA improves the outcome in stroke
patients. Mechanical thrombectomy is now the preferred treatment for patients
with acute ischemic stroke resulting from a large-artery occlusion in the
anterior circulation. However, the widespread use of mechanical thrombectomy is
limited by two factors. First, only ~ 10% of patients with acute ischemic stroke
have a proximal large-artery occlusion in the anterior circulation and present
early enough to undergo mechanical thrombectomy within 6 h; an additional 9-10%
of patients presenting within the 6-24-h time window may also qualify for the
procedure. Second, not all stroke centers have the resources or expertise to
perform mechanical thrombectomy. Nonetheless, patients who present to hospitals
where thrombectomy is not an option can receive intravenous t-PA, and those with
qualifying anterior circulation strokes can then be transferred to tertiary
stroke centers where thrombectomy is available. Therefore, despite the advances
afforded by mechanical thrombectomy, there remains a need for treatments that
improve the efficacy and safety of thrombolytic therapy. In this review, we
discuss: (i) current treatment options for acute ischemic stroke; (ii) the
mechanism of action of fibrinolytic agents; and (iii) potential strategies to
manipulate the fibrinolytic system to promote endogenous fibrinolysis or to
enhance the efficacy of fibrinolytic therapy.
PMID- 29953718
TI - Super-resolution Imaging of Amyloid Structures over Extended Times by Using
Transient Binding of Single Thioflavin T Molecules.
AB - Oligomeric amyloid structures are crucial therapeutic targets in Alzheimer's and
other amyloid diseases. However, these oligomers are too small to be resolved by
standard light microscopy. We have developed a simple and versatile tool to image
amyloid structures by using thioflavin T without the need for covalent labeling
or immunostaining. The dynamic binding of single dye molecules generates photon
bursts that are used for fluorophore localization on a nanometer scale. Thus,
photobleaching cannot degrade image quality, allowing for extended observation
times. Super-resolution transient amyloid binding microscopy promises to directly
image native amyloid by using standard probes and record amyloid dynamics over
minutes to days. We imaged amyloid fibrils from multiple polypeptides,
oligomeric, and fibrillar structures formed during different stages of amyloid
beta aggregation, as well as the structural remodeling of amyloid-beta fibrils by
the compound epi-gallocatechin gallate.
PMID- 29953717
TI - Risk of hypertension after hysterectomy: a population-based study.
AB - OBJECTIVE: Hysterectomy is the second most common surgery performed mainly for
benign uterine pathologies in females. The association between hysterectomy and
the subsequent risk of hypertension remains controversial. This study
investigated the risk of developing hypertension in women who had a hysterectomy.
DESIGN: Population-based retrospective cohort study. SETTING: We used the Taiwan
National Health Insurance Research Database with claims data of 1 million
randomly selected insured individuals. POPULATION: Women with and without
hysterectomy and bilateral salpingo-oophorectomy, aged 30-49 years, were
identified in 2000-2013 from the insurance data. METHODS: From the claims data,
we identified 6674 women with hysterectomy without hypertension at the time of
the surgery. The comparison cohort were 26 696 women randomly selected from women
without hysterectomy and hypertension, matched by age and the year hysterectomy
was performed. Adjusted hazard ratio (aHR) of hypertension was estimated after
controlling for comorbidities. MAIN OUTCOME MEASURE: Prediction for hypertension
following hysterectomy for benign disease. RESULTS: Both cohorts had a median age
of 43.9 years. After a median follow up of 6.4 years, the incident hypertension
was higher in the hysterectomy cohort than in the comparison cohort, with an
adjusted hazard ratio (aHR) of 1.35 [95% confidence interval (CI) 1.27-1.44]. The
incidence increased with age, with a higher aHR in hysterectomised women aged 40
49 years (aHR 1.37, 95% CI 1.06-1.83) than in those aged 30-39 years (aHR 1.22,
95% CI 1.02-1.46). CONCLUSION: Findings in this study suggest that women with
hysterectomy are more likely to be diagnosed with hypertension in the follow-up
period. TWEETABLE ABSTRACT: Women with hysterectomy before 50 years of age are at
an increased risk of developing subsequent hypertension. PLAIN LANGUAGE SUMMARY:
Hysterectomy is one of the most common surgeries for women with benign uterine
disease. Hysterectomy may lead to a sudden decline in the production of sex
hormone (estrogen and progesterone), which is responsible for vessel wall
endothelial dysfunction leading to hardening of arteries and subsequent
hypertension. However, the association between hysterectomy and risk of
hypertension remains controversial. This study investigated whether premenopausal
women have an elevated risk of hypertension after hysterectomy. This study
employed the Taiwan National Health Insurance Research Database to identify 6674
women 30-49 years old who had a hysterectomy between 2000 and 2013, and a
comparison group of 26 696 women who did not have a hysterectomy matched by age.
Women in both the groups had no hypertension at baseline (recruiting date or
within 1 year after recruiting date). By the end of 2013, we found that 1196
(17.9%) and 3613 (13.5%) women had developed hypertension in the hysterectomy and
the comparison groups, respectively. The hypertension incidence was 1.4-fold
greater in the hysterectomy group than in the control group (27.8 versus
20.2/1000 person-years).
PMID- 29953719
TI - Conjunctival bacterial flora and antimicrobial susceptibility of captive and free
living sea turtles in Brazil.
AB - PURPOSE: To describe the aerobic conjunctival bacterial flora of 3 especies of
free-living and under human care sea turtles and determine its antimicrobial
susceptibility in vitro. METHOD: Thirty-six sea turtles (72 eyes), juveniles and
adults, 7 free-living Chelonia mydas and 8 Chelonia mydas, 4 Caretta caretta, 11
Eretmochelys imbricata, and 6 Lepidochelys olivacea under human care, were
evaluated. Conjunctival cultures were collected for identification of aerobic
bacteria and antimicrobial susceptibility testing for ciprofloxacin,
chloramphenicol, gentamicin, neomycin, oxacillin, polymyxin B, tetracycline, and
tobramycin using antibiotic disks. Bacterial strains showing no sensitivity to 4
or more antimicrobials were considered multiresistant to this panel. RESULTS:
Bacterial growth was observed in 12/14 (85.71%) samples in the free-living sea
turtles, and there was growth in 100% (58/58) of the samples from captive
animals. There were 94 strains isolated and 15 species identified. There was a
predominance of Gram-positive bacteria in free-living Chelonia mydas, most of
which were Bacillus and Staphylococcus. The most commonly isolated Gram-negative
species were enterobacteria for free-living and under human care animals. The
strains were predominantly sensitive to ciprofloxacin and tobramycin, and less
sensitive to oxacillin or polymyxin B. Ten multiresistant strains were isolated.
Yeast were identified in 13.89% (10/72) of the samples. CONCLUSIONS: These
results, showing differences in the conjunctival bacterial flora of free-living
and captive animals, may be helpful for diagnosis and treatment of ocular
disorders in sea turtles.
PMID- 29953720
TI - The diagnostic accuracy of laser Doppler flowmetry in assessing pulp blood flow
in permanent teeth: A systematic review.
AB - BACKGROUND/AIM: Pulp necrosis is a frequent complication following dental trauma.
The diagnosis of the state of the dental pulp can be challenging as most commonly
used diagnostic tools are subjective and rely on a response from the patient,
potentially making their use unreliable, especially in the child population. The
aim of the study was to systematically review the evidence on the use of laser
Doppler flowmetry in the assessment of the pulp status of permanent teeth
compared to other sensibility and/or vitality tests. METHODS: A systematic
literature search, using MEDLINE, EMBASE, Cochrane Central Register of Controlled
Trials, www.clinicaltrials.gov and www.controlled-trials.com, in addition to
citation and manual reference list searches, was conducted up to 15th January
2018. A risk of bias assessment was performed using the quality assessment for
diagnostic accuracy studies tool (QUADAS-2) with all steps performed
independently by two reviewers. RESULTS: Four studies with a high risk of bias
were included in the final analysis. Laser Doppler flowmetry was reported to be
more accurate in differentiating between teeth with normal pulps and pulp
necrosis with a sensitivity of (81.8%-100%) and specificity of 100% in comparison
to other vitality tests such as pulp oximetry (sensitivity = 81.3%, specificity =
94.9%) and sensibility tests such as electric pulp testing (sensitivity = 63.3%
91.5%, specificity = 88%-100%). CONCLUSION: Despite the higher reported
sensitivity and specificity of laser Doppler flowmetry in assessing pulp blood
flow, these data are based on studies with a high level of bias and serious
shortfalls in study designs. More research is needed to study the effect of
different laser Doppler flowmetry's parameters on its diagnostic accuracy and the
true cut-off ratios over which a tooth could be diagnosed as having a normal
pulp.
PMID- 29953721
TI - Tricyclic amine antidepressants suppress beta-lactam resistance in methicillin
resistant Staphylococcus aureus (MRSA) by repressing mRNA levels of key
resistance genes.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of
recurrent infections in humans including endocarditis, pneumonia, and toxic shock
syndrome. Novel therapeutics to treat MRSA and other resistant bacteria are
urgently needed. Adjuvant therapy, which uses a non-toxic compound to
repotentiate the toxic effects of an existing antibiotic, is an attractive
response to the growing resistance crisis. Herein, we describe the evaluation of
structurally related, FDA-approved tricyclic amine antidepressants that
selectively repotentiate MRSA to beta-lactam antibiotics. Our results identify
important structural features of the tricyclic amine class for beta-lactam
adjuvant activity. Furthermore, we describe the mechanism of action for our lead
compound, amoxapine, and illustrate that it represses the mRNA levels of key beta
lactam resistance genes in response to beta-lactam treatment. This work is novel
in that it highlights an important class of small molecules with the ability to
simultaneously inhibit production of both beta-lactamase and penicillin binding
protein 2a.
PMID- 29953722
TI - Nickel Doping in Atomically Thin Tin Disulfide Nanosheets Enables Highly
Efficient CO2 Reduction.
AB - Engineering electronic properties by elemental doping is a direct strategy to
design efficient catalysts towards CO2 electroreduction. Atomically thin SnS2
nanosheets were modified by Ni doping for efficient electroreduction of CO2 . The
introduction of Ni into SnS2 nanosheets significantly enhanced the current
density and Faradaic efficiency for carbonaceous product relative to pristine
SnS2 nanosheets. When the Ni content was 5 atm %, the Ni-doped SnS2 nanosheets
achieved a remarkable Faradaic efficiency of 93 % for carbonaceous product with a
current density of 19.6 mA cm-2 at -0.9 V vs. RHE. A mechanistic study revealed
that the Ni doping gave rise to a defect level and lowered the work function of
SnS2 nanosheets, resulting in the promoted CO2 activation and thus improved
performance in CO2 electroreduction.
PMID- 29953724
TI - Sterically Crowded Trianglimines-Synthesis, Structure, Solid-State Self-Assembly,
and Unexpected Chiroptical Properties.
AB - The chiral, triangular-shape hexaimine macrocycles (trianglimines), bearing bulky
alkynyl or aryl substituents were synthesized and studied by means of
experimental and theoretical methods. The macrocyclization reactions are driven
by the extraordinary stability of the trianglimine ring and provided products
with high yields. Electrostatic repulsion between imine nitrogen atoms and the
substituents forced an anti conformation of the aromatic linkers. Although the
DFT-optimized structure of 7 is D3 symmetrical, in the crystal, the macrocycle
adopts a bowl-like molecular shape. The macrocycle self-assembles into tail-to
tail dimers by mutual interdigitation of aromatic moieties. In contrast,
macrocycle 8 adopts a rigid pillararene-like conformation. The nature of the
substituent significantly affects the electronic properties of the linker. As a
result, unexpectedly high exciton Cotton effects are observed in the electronic
circular dichroism (ECD) spectra. The origin of these effects was subject of an
in-depth study.
PMID- 29953723
TI - Stimulation of exosome release by extracellular DNA is conserved across multiple
cell types.
AB - Exosomes are distinguished from other types of extracellular vesicles by their
small and relatively uniform size (30-100 nm) and their composition which
reflects their endo-lysosomal origin. Involvement of these extracellular
organelles in intercellular communication and their implication in pathological
conditions has fuelled intensive research on mammalian exosomes; however,
currently, very little is known about exosomes in lower vertebrates. Here we show
that, in primary cultures of head kidney leukocytes from Atlantic salmon (Salmo
salar), phosphorothioate CpG oligodeoxynucleotides induce secretion of vesicles
with characteristics very similar to these of mammalian exosomes. Further
experiments revealed that the oligonucleotide-induced exosome secretion did not
depend on the CpG motifs but it relied on the phosphorothioate modification of
the internucleotide linkage. Exosome secretion was also induced by genomic
bacterial and eukaryotic DNA in toll-like receptor 9-negative piscine and human
cell lines demonstrating that this is a phylogenetically conserved phenomenon
which does not depend on activation of immune signaling pathways. In addition to
exosomes, stimulation with phosphorothioate oligonucleotides and genomic DNA
induced secretion of LC3B-II, an autophagosome marker, which was associated with
vesicles of diverse size and morphology, possibly derived from autophagosome
related intracellular compartments. Overall, this work reveals a previously
unrecognized biological activity of phosphorothioate ODNs and genomic DNA - their
capacity to induce secretion of exosomes and other types of extracellular
vesicles. This finding might help shed light on the side effects of therapeutic
phosphorothioate oligodeoxynucleotides and the biological activity of
extracellular genomic DNA which is often upregulated in pathological conditions.
PMID- 29953725
TI - A Small Library of 1,2,3-Triazole Analogs of CAP-55: Synthesis and Binding
Affinity at Nicotinic Acetylcholine Receptors.
AB - Alpha7 nicotinic acetylcholine receptor is emerging as a central regulator in
inflammatory processes, as documented by increasing studies reported in the
literature. For instance, the activation of this nicotinic receptor subtype in
resident macrophages inhibits the production of pro-inflammatory cytokines,
thereby attenuating local inflammatory responses, and may open a new window in
the treatment of chronic inflammatory disease, such as Crohn's disease,
rheumatoid arthritis, psoriasis, and asthma. In continuation of our ongoing
research for the development of new cholinergic drug candidates, we selected the
nicotine derivative CAP55, which was previously shown to exert anti-inflammatory
effects via nicotinic stimulation, as a suitable compound for lead optimization.
Through the isosteric replacement of its 3,5-disubstituted 4,5-dihydroisoxazole
core with a 1,4-disubstituted 1,2,3-triazole ring, we could rapidly generate a
small library of CAP55-related analogs via a one-pot copper(I)-catalyzed azide
alkyne cycloaddition. Receptor binding assays at nAChRs led to the identification
of two promising derivatives, compounds 4 and 10, worthy of further
pharmacological studies.
PMID- 29953726
TI - Patterns of hospital admission in 54 501 patients with epistaxis over a 20-year
period in Scotland, UK.
AB - BACKGROUND: Epistaxis affects most people over their lifetime. It is the
commonest ear, nose and throat emergency. Hospital admission and socio-economic
deprivation have been associated with mental health disorders, respiratory
illness and with emergency hospital admissions. Low socio-economic status has
never previously been associated with epistaxis, a common reason for admission to
ear, nose and throat departments throughout the UK. METHODS: Demographics from
Information Services Division Scotland were analysed over a period of 20 years.
This focused on gender, number of admissions, number of bed days, socio-economic
deprivation (Scottish Index of Multiple Deprivation) and mortality within 1 year.
RESULTS: Data from 54 501 patients were assessed. Admission numbers and length of
stay have significantly decreased (P < 0.0001). Males are more frequently
affected (P = 0.001). Admission numbers were higher for patients in more deprived
areas (P < 0.001). Mean duration of stay has decreased by 1 bed day. Surgical
intervention of epistaxis has increased significantly (P < 0.001). There is an
associated 1-year mortality rate of 9.8% following epistaxis. CONCLUSION: There
has been a significant decrease in hospital admissions and length of hospital
stay in patients admitted with epistaxis over the past 20 years. There is a
significant association with deprivation and epistaxis admission.
PMID- 29953727
TI - Sinapic acid phenethyl ester as a potent selective 5-lipoxygenase inhibitor:
Synthesis and structure-activity relationship.
AB - Given the hepatotoxicity and an unfavorable pharmacokinetic profile of zileuton
(Zyflo(r) ), currently the only approved and clinically used 5-Lipoxygenase (5
LO) inhibitor, the search for potent and safe 5-LO inhibitors is highly demanded.
The action of several phenolic acid phenethyl esters as potential 5-Lipoxygenase
(5-LO) inhibitors has been investigated. For this purpose, a series of 14
phenethyl esters was synthesized and their impact on 5-LO inhibition was
evaluated. The effects of position and number of hydroxyl and methoxy groups on
the phenolic acid were investigated. The shortening of the linker between the
carbonyl and the catechol moiety as well as the presence of the alpha,beta
unsaturated carbonyl group was also explored. The sinapic acid phenethyl ester
(10), which can be named SAPE (10) by analogy to caffeic acid phenethyl ester
(CAPE), inhibited 5-LO in a concentration-dependent manner and outperformed both
zileuton (1) and CAPE (2). With an IC50 of 0.3 MUm, SAPE (10) was threefold more
potent than CAPE (2) and 10-fold more potent than zileuton (1), the only 5-LO
inhibitor approved for clinical use. Unlike CAPE (2), SAPE (10) had no effect on
12-lipoxygenase (12-LO) and less effect on cyclooxygenase 1 (COX-1) which makes
it a more selective 5-LO inhibitor.
PMID- 29953728
TI - CHIP promotes autophagy-mediated degradation of aggregating mutant p53 in hypoxic
conditions.
AB - Tumor suppressor protein p53 aggregates in the hypoxic core of solid tumors. C
terminus of Hsc70-interacting protein (CHIP) displays chaperone as well as E3
ligase activities in both stabilizing and degrading wild-type and mutant p53. In
this study, we have discovered that CHIP selectively degrades aggregating mutant
p53 under both normal and hypoxic conditions. Silencing of CHIP alleviates
degradation of aggregating mutant p53 in both normoxia and hypoxia, but has no
significant effect on the level of nonaggregating mutant p53. Although both U-box
and TPR domains of CHIP are responsible for p53 degradation, the U-box domain
selectively binds to aggregating mutant p53, whereas the TPR domain interacts
with nonaggregating mutant p53. The degradation of mutant p53 by CHIP is shown to
be via autophagy through K63-linked polyubiquitination. Both in normoxia and
under physiological hypoxia, the level of aggregating mutant p53 in the presence
of CHIP was reduced threefold, whereas under serum starvation, it was reduced
fivefold. Interestingly, both wild-type and mutant p53 interact with and
stabilize CHIP at the post-translational level, suggesting a chaperone synergy
between p53 and CHIP. This finding may have strong therapeutic significance via
selective degradation of oncogenic mutant p53 in regressing hypoxic tumors.
PMID- 29953729
TI - Minimal clinically important difference for the 22-item Sinonasal Outcome Test in
medically managed patients with chronic rhinosinusitis.
AB - OBJECTIVE: To determine the minimal clinically important difference (MCID) of the
22-item Sinonasal Outcome Test (SNOT-22) in individuals undergoing medical
management for their chronic rhinosinusitis (CRS). DESIGN: Prospective
observational study. SETTING: Academic, tertiary care centre. PARTICIPANTS: A
total of 247 adults undergoing medical management for CRS. MAIN OUTCOME MEASURE:
At enrolment, participants completed a SNOT-22. At a subsequent follow-up visit,
2-12 months after enrolment, participants also completed a SNOT-22. At follow-up,
participants also rated the change in their sinus symptoms and general health as
"Much worse," "A little worse," "About the same," "A little better" or "Much
better" compared with enrolment; these two questions were used as sinus symptom
and general health anchor questions, respectively. The SNOT-22 MCID was
calculated using distribution-based, anchor-based and receiver operating
characteristic (ROC) curve-based methods. RESULTS: Using the distribution-based
method, the SNOT-22 MCID was 11.6. Using the sinus symptom anchor question, the
SNOT-22 MCID was 10.5; applying the ROC method to the sinus symptom anchor
yielded an MCID of 12.5. In comparison, using the general health anchor question,
the SNOT-22 MCID was 8.3; applying the ROC method to the sinus symptom anchor
yielded an MCID of 17.5. In all cases, the calculated MCID had a sensitivity of
approximately 50-60% and specificity of approximately 80-90%. CONCLUSIONS: Based
on our results, we propose a SNOT-22 MCID of 12 in medically managed patients
with CRS. The MCID, while specific, was not sensitive for identifying patients
with CRS experiencing a noticeable improvement in sinus symptoms or general
health.
PMID- 29953730
TI - Structure-Guided Engineering of alpha-Keto Acid Decarboxylase for the Production
of Higher Alcohols at Elevated Temperature.
AB - Branched-chain keto acid decarboxylases (KDCs) are a class of enzymes that
catalyze the decarboxylation of alpha-keto acids. They are key enzymes for
production of higher alcohols in vivo and in vitro. However, the two most active
KDCs (KivD and KdcA) have only moderate thermostability (<55 degrees C), which
hinders the production of alcohols at high temperatures. Herein, structure-guided
engineering toward improved thermostability of KdcA is outlined. Strategies such
as stabilization of the catalytic center, surface engineering, and optimization
of dimer interactions were applied. With seven amino acid substitutions, variant
7M.D showed an increase of the temperature at which 50 % of activity remains
after one-hour incubation T1h50 by 14.8 degrees C without compromising its
substrate specificity. 7M.D exhibited greater than 400-fold improvement of half
life at 70 degrees C and greater than 600-fold increase in process stability in
the presence of 4 % isobutanol at 50 degrees C. 7M.D is more promising for the
production of higher alcohols in thermophiles (>65 degrees C) and in cell-free
applications.
PMID- 29953731
TI - Evolution of living donor liver transplantation: a global perspective.
PMID- 29953732
TI - Vitamin D3 supplementation improves testicular function in diabetic rats through
peroxisome proliferator-activated receptor-gamma/transforming growth factor-beta
1/nuclear factor-kappa B.
AB - AIMS/INTRODUCTION: Vitamin D3 deficiency can lead to male hypogonadism in
diabetes mellitus, but the target organs and the mechanism driving the disorder
are unclear. This experiment was designed to study the relationship between
vitamin D3 deficiency and hypogonadism in diabetes mellitus. MATERIALS AND
METHODS: Rats with streptozotocin-induced diabetes were randomly divided into
four groups and treated with different doses of vitamin D3 : blank (no vitamin D3
), low (0.025 MUg/kg/day), high (0.1 MUg/kg/day), high (0.1 MUg/kg/day) and with
bisphenol A diglycidyl ether (peroxisome proliferator-activated receptor gamma
inhibitor 30 mg/kg/day). They were compared with wild-type rats. RESULTS: After
12 weeks, the vitamin D3 supplements had partially restored testicular
pathological changes, as shown by reduced testicular fibrosis related to
downregulation transforming growth factor beta 1 and apoptosis related to
downregulation of nuclear factor kappa B, but not the pituitary gland. The
expression of peroxisome proliferator-activated receptor gamma, which can inhibit
transforming growth factor beta 1 and nuclear factor kappa B, was significantly
increased after treatment with vitamin D3 . CONCLUSIONS: These results suggest
that treatment with vitamin D3 can improve testicular function in diabetic rats
through the peroxisome proliferator-activated receptor gamma/transforming growth
factor beta 1/nuclear factor kappa B signaling pathway.
PMID- 29953733
TI - Preference phenotypes can be used to support shared decision-making at point-of
care for patients with rheumatoid arthritis: A proof of concept study.
AB - OBJECTIVE: In this proof-of-concept study, we sought to evaluate whether a value
clarification tool enabling patients to view a set of rheumatoid arthritis (RA)
treatment preference phenotypes could be used to support shared decision-making
(SDM) at the point-of-care. METHODS: We conducted a pre-post test study. All
English-speaking RA patients presenting to their scheduled outpatient visits were
asked to participate. Visits for patients with active RA were transcribed. SDM
components were measured using a quantitative coding scheme based on an
established model of SDM. RESULTS: Forty-six visits were included in the pre-test
and 40 in the post-test phase. Providers offered more DMARDs (two or more) in the
post-test visits (60%) compared to the pre-test visits (47.8%). Overall, more
patients vocalized their values and/or preferences in the post-test visits
compared to the pre-test visits for treatment escalation decisions including
choice of one new DMARD (90.9% versus 56.3%), two or more new DMARDs (95.8%
versus 86.4%), as well as prednisone (87.5% versus 66.7%). Providers were also
more likely to base their recommendations on patients' values and/or preferences
in the post-test (100% of six visits) than pre-test (64.3% of 14 visits) phase
during visits in which a recommendation was made. The average (SD) length of the
visit was 29.9 (11.6) minutes and 25.1 (10.7) minutes in the pre- and post-test
phases respectively. CONCLUSION: This study provides an early indication that a
value clarification tool allowing patients to consider a set of preference
phenotypes can support SDM at the point-of-care without extending visit time.
This article is protected by copyright. All rights reserved.
PMID- 29953734
TI - Expression and Purification of Recombinant Proteins Using the Baculovirus System.
AB - This article describes how to analyze protein expression in cells infected with
recombinant baculovirus on a small scale for optimizing protein production, how
to maximize and scale up recombinant protein production, and how to purify
recombinant proteins. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29953735
TI - Response surface design as a powerful tool for the development of environmentally
benign HPLC methods for the determination of two antihypertensive combinations:
Greenness assessment by two green analytical chemistry evaluation tools.
AB - Interest in implementing green chemistry principles in analytical chemistry has
grown dramatically in the past few years. The solvents used have the major
influence on the greenness of the method. Most conventional high-performance
liquid chromatography methods employed utilize solvents that are "hazardous for
the environment". In the present study, two-factor three-level response surface
design was exploited to develop eco-friendly chromatographic methods for two
different mixtures. The first one was atorvastatin and amlodipine and the second
one was amlodipine, perindopril, and indapamide. As it is nontoxic to the
environment, ethanol was used as the organic modifier in the mobile phase. The
separation of the first mixture was attained using phosphate buffer (pH
7)/ethanol (42:58 v/v), and the second mixture was fully resolved using phosphate
buffer (pH 5)/ethanol (40:60 v/v). The use of high-performance liquid
chromatography allows excellent resolution in a short run time, hence, less waste
was produced. The greenness of the developed methods was assessed by two
evaluation tools, namely, National Environmental Methods Index and analytical eco
scale, and found to be excellent green analytical methods. Moreover, the
developed methods were compared with other reported methods regarding accuracy
and greenness and were found to be perfect alternatives to reported methods for
separation and quantification of the mixtures.
PMID- 29953736
TI - Value of incorporating newly identified risk factors into risk prediction for
chemotherapy-induced febrile neutropenia.
AB - Several comorbidities have recently been shown to affect risk of chemotherapy
induced febrile neutropenia (FN). Here, we evaluated the added predictive value
of these comorbidities beyond established FN risk factors. A retrospective cohort
study was conducted among adult patients diagnosed with cancer and treated with
chemotherapy at Kaiser Permanente Southern California between 2000 and 2009. The
study cohort was equally split into training and validation datasets to develop
and evaluate the performance of FN risk prediction models in the first
chemotherapy cycle. A reference model was developed based on the model proposed
by Lyman et al (Cancer 2011;117:1917). A new model was developed by incorporating
the newly identified comorbidities such as rheumatoid conditions and thyroid
disorders into the reference model. Area under the receiver operating
characteristic curve (AUROCC), risk reclassification, and integrated
discrimination improvement (IDI) were used to evaluate the potential improvement
of FN risk prediction by incorporating comorbidities. A total of 15 279 patients
were included; 4.2% experienced FN in the first chemotherapy cycle. Including
comorbidities in FN risk prediction did not improve AUROCC (reference model 0.71
vs new model 0.72). A significant improvement in individual-level FN risk
prediction was indicated by IDI (P = .02). However, significant improvement in
risk reclassification was not observed overall (although 6% of all patients were
more accurately classified for their FN risk level, 5% were less accurately
classified) or when examining predicted FN risk among patients who did and did
not develop FN. Incorporating several new comorbidities into FN prediction led to
improved FN risk prediction in the first chemotherapy cycle, although the
observed improvements were small and might not be clinically relevant.
PMID- 29953737
TI - Gunn rats with glial activation in the hippocampus show prolonged immobility time
in the forced swimming test and tail suspension test.
AB - INTRODUCTION: Recent studies imply that glial activation plays a role in the
pathogenesis of psychiatric disorders, such as schizophrenia and major
depression. We previously demonstrated that Gunn rats with hyperbilirubinemia
show congenital gliosis and schizophrenia-like behavior. METHODS: As it has been
suggested that major depression involves glial activation associated with
neuroinflammation, we examined whether Gunn rats show depression-like behavior
using the forced swimming test (FST) and the tail suspension test (TST). In
addition, we quantitatively evaluated both microgliosis and astrogliosis in the
hippocampus of Gunn rats using immunohistochemistry analysis of the microglial
marker ionized calcium-binding adaptor molecule (Iba) 1 and the astrocytic marker
S100B. RESULTS: Both the FST and TST showed that immobility time of Gunn rats was
significantly longer than that of normal control Wistar rats, indicating that
Gunn rats are somewhat helpless, a sign of depression-like behavior. In the
quantification of immunohistochemical analysis, Iba1immunoreactivity in the
dentate gyrus (DG), cornu ammonis (CA) 1, and CA3 and the number of Iba1-positive
cells in the CA1 and CA3 were significantly increased in Gunn rats compared to
Wistar rats. S100B immunoreactivity in the DG, CA1, and CA3 and the number of
S100B-positive cells in the DG and CA3 were significantly increased in Gunn rats
compared to Wistar rats. CONCLUSION: Our findings suggest that both microglia and
astrocyte are activated in Gunn rats and their learned helplessness could be
related to glial activation.
PMID- 29953738
TI - A new niclosamide derivatives-B17 can inhibit urological cancers growth through
apoptosis-related pathway.
AB - The incidence and mortality rate of urological cancers is increasing yearly.
Niclosamide has been repurposed as an anti-cancer drug in recent years.
Synthesized derivative of niclosamide was testified for its anti-cancer activity
in urological cancers. MTT assay was used to measure the cytotoxicity effect of
niclosamide and its derivatives in urological cancer cell lines. Migratory
ability was monitored by scratch migration assay. Apoptosis and cell cycle
changes were analyzed by annexin V and PI staining. The apoptosis-related signal
proteins were evaluated by western blotting. T24 had the best drug sensitivity
with the lowest IC50 in niclosamide and B17 treatment than DU145 and Caki-1
cells. After niclosamide and B17 treatment, the mitotic cells were decreased, but
apoptotic bodies and morphology changes were not prominent in T24, Caki-1, and
DU145 cells. The migratory ability was inhibited in niclosamide treatment than
control group on Caki-1 cells and niclosamide and B17 treatment than control
group on DU145 cells. Early apoptosis cells were increased after niclosamide and
B17 treatment than control group without cell cycle changes in T24, Caki-1, and
DU145 cells. Programmed cell death was activated majorly through PAPR and bcl-2
in T24 and caspase-3 in Caki-1 cells, respectively. Niclosamide and B17
derivative had good ability in inhibition proliferation and migratory ability in
T24, Caki-1, and DU145 cells without prominent morphology and apoptotic body
changes. UCC cells are more sensitive to niclosamide and B17 treatment. Early
apoptosis was induced after niclosamide and B17 treatment through different
mechanisms in T24, Caki-1, and DU145 cells.
PMID- 29953739
TI - The Association Between Nailfold Capillary Density and Pulmonary and Cardiac
Involvement in Medium- to Long-standing Juvenile Dermatomyositis.
AB - OBJECTIVE: To explore the associations between microvascular abnormalities
assessed by nailfold capillaroscopy (NFC) and pulmonary and cardiac involvement
in patients with juvenile dermatomyositis (DM) assessed after medium- to long
term follow-up. METHODS: Fifty-eight juvenile DM patients were examined mean 17.0
(SD 10.6) years after symptom onset. Nailfold capillary density (NCD) and
neovascular pattern (defined as scleroderma active or late pattern) were analysed
blinded to clinical data. Pulmonary involvement was assessed by pulmonary
function tests (PFT) including spirometry, diffusion capacity for carbon monoxide
(DLCO) and body plethysmography; also high-resolution computed tomography (HRCT)
was performed. Cardiac involvement was assessed by electrocardiography, Holter
monitoring (heart rate variability) and echocardiography. RESULTS: Patients with
low NCD (<6 capillaries/mm) (n=21), compared to patients with normal NCD (>= 6
capillaries/mm) (n=37), presented lower forced vital capacity (89.7 vs 98.5% of
predicted), total lung capacity (87.8 vs 94.5% of predicted) and more often low
DLCO (15/21 (71%) vs 14/37 (38%)); all p's<0.05. HRCT assessed airways disease
was more frequent in the low NCD group (6/21 (30%) vs 3/37 (8%); p=0.034). No
associations were found between i) NCD and cardiac parameters or ii) neovascular
pattern and pulmonary or cardiac parameters. CONCLUSION: In juvenile DM patients,
low NCD was associated with lung involvement, which was mostly subclinical. No
significant associations with cardiac involvement were found. These results shed
light on possible mechanisms underlying organ involvement, but further and
preferably larger studies are needed to identify NCD as a potential biomarker for
lung and cardiac involvement in juvenile DM. This article is protected by
copyright. All rights reserved.
PMID- 29953740
TI - Liraglutide Decreases Hepatic Inflammation and Injury in Advanced Lean Non
Alcoholic Steatohepatitis.
AB - Although commonly associated with obesity, non-alcoholic fatty liver disease
(NAFLD) is also present in the lean population representing a unique disease
phenotype. Affecting 25% of the world's population, NAFLD is associated with
increased mortality especially when progressed to non-alcoholic steatohepatitis
(NASH). However, no approved pharmacological treatments exist. Current research
focuses mainly on NASH associated with obesity, leaving the effectiveness of
promising treatments in lean NASH virtually unknown. This study therefore aimed
to evaluate the effect of liraglutide (glucagon-like peptide 1 analogue) and
dietary intervention, alone and in combination, in guinea pigs with non-obese
NASH. After 20 weeks of high-fat feeding (20% fat, 15% sucrose, 0.35%
cholesterol), 40 female guinea pigs were block-randomized based on weight into
four groups receiving one of four treatments for 4 weeks: continued high-fat diet
(HF, control), high-fat diet and liraglutide treatment (HFL), chow diet (4% fat,
0% sucrose, 0% cholesterol; HFC) or chow diet and liraglutide treatment (HFCL).
High-fat feeding induced NASH with severe fibrosis. Liraglutide decreased
inflammation (p < 0.05) and hepatocyte ballooning (p < 0.05), while increasing
hepatic alpha-tocopherol (p = 0.0154). Dietary intervention did not improve liver
histopathology significantly, but decreased liver weight (p = 0.004), plasma
total cholesterol (p = 0.0175), LDL-cholesterol (p = 0.0063), VLDL-cholesterol (p
= 0.0034), hepatic cholesterol (p < 0.0001) and increased hepatic vitamin C (p =
0.0099). Combined liraglutide and dietary intervention induced a rapid weight
loss, necessitating periodical liraglutide dose adjustment/discontinuation,
limiting the strength of the findings from this group. Collectively, this pre
clinical study supports the beneficial effect of liraglutide on NASH and extends
this notion to lean NASH.
PMID- 29953741
TI - Gaps in Mental Health Care for Youth with Rheumatologic Conditions: A Mixed
Methods Study of Perspectives from Behavioral Health Providers.
AB - OBJECTIVE: To identify behavioral health provider perspectives on gaps in mental
health care for youth with rheumatologic conditions. METHODS: Social workers
(n=34) and psychologists (n=8) at pediatric rheumatology centers in the Childhood
Arthritis and Rheumatology Research Alliance (CARRA) completed an online survey
assessing current practices and mental health care needs of youth with
rheumatologic conditions. Responses were compared to a published survey of CARRA
rheumatologists (n=119). Thematic analysis of 20 semi-structured interviews with
behavioral health providers was performed. RESULTS: One third of CARRA centers
(n=100) had no affiliated social worker or psychologist. Only one behavioral
health provider reported current universal mental health screening at their
rheumatology clinic, yet routine depression screening was supported by >85% of
behavioral health providers and rheumatologists. Support for anxiety screening
was higher among behavioral health providers (90% vs 65%, p<0.01). Interviews
illustrated a need for interventions addressing illness-related anxiety,
adjustment/coping/distress, transition, parent/caregiver mental health, and peer
support. Limited resources, lack of protocols, and patient cost/time burden were
the most frequent barriers to intervention. Inadequate follow-up of mental health
referrals was indicated by 52%. More behavioral health providers than
rheumatologists favored mental health services in rheumatology settings (55% vs
19%, p<0.01). Only 7 social workers (21%) provided counseling/therapy, and
interviews indicated their perceived under-utilization for these services.
CONCLUSION: Behavioral health providers indicate an unmet need for mental health
interventions addressing illness-related issues affecting youth with
rheumatologic conditions. Implementation of mental health protocols and
optimizing utilization of social workers may improve mental health care for these
youth. This article is protected by copyright. All rights reserved.
PMID- 29953742
TI - Relationship of Joint Hypermobility with Ankle and Foot Radiographic
Osteoarthritis and Symptoms in a Community-Based Cohort.
AB - OBJECTIVE: To explore associations of joint hypermobility (a condition where
range of motion is greater than normal) with ankle and foot radiographic
osteoarthritis and symptoms in a large community-based cohort of African American
and Caucasian adults 55-94 years old. METHODS: Ankle and foot radiographs and
joint hypermobility data (Beighton Criteria) were available for 848 participants
(2003-2010) in this cross-sectional study. General joint hypermobility was
defined as a Beighton score >=4 (range 0-9); knee hypermobility was defined as
hyperextension of at least one knee. Standing anteroposterior and lateral foot
radiographs were read with standard atlases for Kellgren-Lawrence grade,
osteophytes and joint space narrowing at the tibiotalar joint and for osteophytes
and joint space narrowing to define osteoarthritis at five foot joints. Ankle or
foot symptoms were self-reported. Separate person-based logistic regression
models were used to estimate associations of ankle and foot osteoarthritis and
symptom outcomes with hypermobility measures, adjusting for age, sex, race, body
mass index, and history of ankle/foot injury. RESULTS: This sample was: 68% women
and 33% African American; mean age=71 years; mean body mass index=31 kg/m2 ;
general joint hypermobility=7%, knee hypermobility=4%; ankle injury=11.5%, foot
injury=3.8%. Although general joint hypermobility was not associated with ankle
and foot outcomes, knee hypermobility was associated with ankle symptoms, foot
symptoms, and talonavicular osteoarthritis (adjusted odds ratios of 4.4, 2.4, and
3.0, respectively). CONCLUSIONS: Knee joint hypermobility may be related to
talonavicular osteoarthritis and to ankle and foot symptoms. This article is
protected by copyright. All rights reserved.
PMID- 29953743
TI - 18 F-Fluorodeoxyglucose positron emission tomography can be used to determine the
indication for endoscopic resection of superficial esophageal cancer.
AB - 18 F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful
imaging modality that reflects the tumor activity. However, FDG-PET is mainly
used for advanced cancer, not superficial cancer. In this study, we investigated
the relationship between the superficial tumor depth of esophageal cancer and the
FDG uptake to determine the indications for endoscopic resection (ER). From 2009
to 2017, 444 patients with esophageal cancer underwent esophagectomy or
endoscopic submucosal dissection (ESD), and 195 patients were pathologically
diagnosed with superficial cancer. Among them, 146 patients were examined by FDG
PET before esophagectomy or ESD. In these 146 patients, the relationship between
the pathological tumor depth and FDG uptake was analyzed. The mean maximum
standardized uptake value in pT1a-EP/LPM tumors was 1.362 +/- 0.890, that in pT1a
MM/pT1b-SM1 tumors was 2.453 +/- 1.872, and that in pT1b-SM2/SM3 tumors was 4.265
+/- 3.233 (P < .0001). Among 51 pT1a-EP/LPM tumors, 10 (19.6%) showed positive
detection of FDG. For pT1a-MM/pT1b-SM1 and pT1b-SM2/SM3 tumors, the detection
rate was 52.9% (18/34) and 82.0% (50/61), respectively. The detection rate of
pT1a-EP/LPM was significantly lower than in the other two groups (P < .0001).
Among 10 FDG-PET-positive lesions, only 1 had no apparent reason for PET
positivity; however, 9 of 10 had a suitable reason for detectability by PET and
inadequacy for ER. Negative detection of superficial esophageal squamous cell
carcinoma by FDG-PET is useful to determine the indication for ER when the tumor
depth cannot be diagnosed even after performing magnifying endoscopy with narrow
band imaging and endoscopic ultrasonography. When FDG uptake is recognized, a
therapeutic modality other than ER should be considered.
PMID- 29953744
TI - Has Rheumatology Become A More Attractive Career Choice? Comparison Of Trends In
The Rheumatology Fellowship Match From 2008 To 2013 With 2014 To 2017.
AB - OBJECTIVE: Rheumatology has been a less attractive career choice than other
internal medicine (IM) subspecialties. Recent fellowship "Match" data suggested
this may have changed. We therefore evaluated the current attractiveness of
rheumatology and compared it with other medical subspecialties. METHODS: Data
from the "Match" from 2008 - 2017, the 2015 American College of Rheumatology
workforce study, and Medscape physician salaries from 2010 - 2017 were used to
determine annual numbers of fellowship applicants, availability of positions, and
post-fellowship salary trends. Data from 2008 - 2013 were compared with 2014 -
2017, and rheumatology with other IM subspecialties. RESULTS: The total number of
annual applicants to rheumatology for 2008 - 2013 decreased from 251 to 244, a 3%
decrease (average annual percentage change of -1.9% +/- 2.6 [mean +/- SEM]).
However, for 2014 - 2017 annual rheumatology applications increased from 230 to
332, a 44% increase (average annual percentage change of 20.7% +/- 10.5 [p =
0.03]). Other non-procedural and procedural IM subspecialties did not exhibit
such an increase. For rheumatology the ratio of annual applicants to positions (p
= 0.02) and percentage of US medical graduates applying (p = 0.03) were
statistically significantly increased, while mean post-fellowship salary also
rose. CONCLUSIONS: These observations suggest that rheumatology has become more
attractive since 2014. We speculate that the increasing popularity of the field
is multifactorial, likely reflecting lifestyle, job satisfaction and
availability, influences of mentors, and other elements. This is a salutary and
potentially exciting opportunity for rheumatology that should be exploited. This
article is protected by copyright. All rights reserved.
PMID- 29953745
TI - Muscle co-activation across activities of daily living in individuals with knee
osteoarthritis.
AB - OBJECTIVE: Muscle co-activation has been shown to be elevated in individuals with
knee osteoarthritis (KOA) during gait. Comparisons of muscle co-activation across
different activities of daily living such as stair negotiation have yet to be
explored. The aim of the study was to explore muscle co-activation across
different activities of daily living in patients with KOA. METHODS: Muscle co
activation was assessed in 77 symptomatic KOA participants (age 62.5+/-8.1years;
body mass index 29.4+/-9.0kg/m2 ; gender 48/29 female/male) using
electromyography (EMG), during a series of walking, stair negotiation (ascent,
descent) and sit-to-walk activities. EMG was recorded from 7 sites,
medial/lateral gastrocnemius, biceps femoris, semitendinosus, vastus
lateralis/medialis and rectus femoris and normalised to maximal voluntary
isometric contraction. Correlation was used to assess the consistency of co
activation across activities. Repeated measures ANOVA assessed the muscle
combination by activity differences. RESULTS: Muscle co-activation was highest
during stair ascent. When comparing muscle combinations within the same activity
correlations ranged from r=0.003-0.897 of which 80% of combinations were
significant. Between activities muscle co-activation was significantly different
(P<0.05). Medial:lateral muscle co-activation was higher than
hamstrings:quadriceps across activities. CONCLUSION: Two muscle co-activation
strategies were observed during activities of daily living in patients with KOA
to maintain stability. Muscle co-activation was higher during more challenging
activities, particularly when the joint is accepting load. Medial:lateral muscle
co-activation was higher than hamstrings:quadriceps whereby medial:lateral co
activation is thought to be a stabilisation mechanism whilst
hamstrings:quadriceps responds to knee flexion moments, suggesting different
muscle combinations may have different roles in responding to joint demand. This
article is protected by copyright. All rights reserved.
PMID- 29953746
TI - Low recurrence rate of head and neck basal cell carcinoma treated with Mohs
micrographic surgery: A retrospective study of 1021 cases.
AB - OBJECTIVE: Mohs micrographic surgery (MMS) is the treatment of choice for high
risk primary basal cell carcinoma (BCC) and recurrent BCC of the head and neck,
showing fewer recurrences compared with surgical excision (SE). The objectives of
this study were to determine the recurrence rate of head and neck BCC after MMS
and to develop a prediction model with significant risk factors for recurrence.
DESIGN: A retrospective study of patient records. METHODS: All BCCs treated with
MMS between 1 January 1995 and 1 July 2013 at the University Medical Center
Groningen (UMCG) were selected retrospectively. Recorded parameters were patient
characteristics, tumour size, tumour location, histopathological subtype,
previous treatment, the number of stages until microscopic clearance, defect
size, adverse events, follow-up time and recurrence after MMS. RESULTS: The study
covered 1021 MMS operations conducted on primary BCCs (57.4%), residual BCCs
(25.6%) and recurrent BCCs (17.0%). The median follow-up time was 54.0 months
(ranging from 1 to 221 months). The 5-year cumulative probability of recurrence
was 3.3%: 2.6% for primary BCCs, 5.4% for residual BCCs and 2.9% for recurrent
BCCs. An aggressive histopathological subtype, residual BCCs and recurrent BCCs
were significant risk factors for predicting a higher risk of recurrence after
MMS. CONCLUSION: This large-scale retrospective study showed low recurrence rates
after MMS for primary and recurrent BCCs. Residual BCCs treated with MMS had
relatively higher recurrence rates. The risk of recurrence for MMS-treated
residual aggressive BCCs was more than four times higher than that for primary
non-aggressive BCCs.
PMID- 29953747
TI - Risk factors for upper tract urothelial recurrence following local excision of
bladder cancer.
AB - The mechanism of upper tract recurrence after local excision of bladder cancer
remains unknown. This study was designed to identify risk factors for upper tract
urothelial recurrence following local tumor excision of bladder cancer. To
identify 76 597 bladder cancer patients, comprising 76 537 nonrecurrence and 60
recurrence patients, the Surveillance, Epidemiology, and End Results database was
used. Kaplan-Meier analysis and univariate and multivariate Cox proportional
hazards regression models were used to determine the risk factors. Compared with
the nonrecurrence group, the recurrence group was associated with older age,
higher grade, high T stage, and higher proportional squamous cell carcinomas.
Univariate Cox proportional hazards regression model showed that age, grades III
and IV, T stage, and pathology were significantly associated with worse upper
tract urothelial recurrence (UTUR) survival. However, after adjusting for
prognostic factors, grade was no longer an independent prognostic factor in
multivariate analysis. This study demonstrates that clinical prognosis of UTUR
after local bladder tumor excision has significant independent risk factors that
include age >=60 years, T1 and T2 stage, and squamous cell carcinoma, and will
require more careful consideration during follow-up.
PMID- 29953748
TI - Limited health literacy predicts patient confusion about patient global
assessments of disease activity and rheumatoid arthritis model disease states.
AB - OBJECTIVE: Visual analog scale patient global assessments (PGA-VAS) are widely
used in rheumatoid arthritis (RA) practice and research. Low PGA-VAS scores are
required for remission. Vulnerable patients may have difficulty completing the
PGA-VAS. There is limited information about both patients' perceptions of PGA-VAS
and how patients score VAS model disease states. The objective of this study is
to understand vulnerable patients' perspectives regarding PGA-VAS and model
disease states. METHODS: We enrolled RA patients at Denver Health (n=300).
Subjects completed the disease activity score-28 (DAS28-PGA-VAS) and
Multidimensional Health Assessment Questionnaire (MDHAQ-PGA-VAS) and completed a
questionnaire regarding these PGA-VAS. Subjects also scored remission, mild,
moderate and severe model disease states by VAS. We performed analyses using
summary statistics, linear, and logistic regression. Outcomes included: whether
subjects found the PGA-VAS confusing, if subjects' responses to the model disease
states followed a natural progression (remission5
CATT repeats in each MIF allele (high genotypic MIF expressers) was 60.2% among
patients with GPA and 53.9% among healthy controls (adjusted P = 0.049). In
response to granulomatous stimulation, human MIF gene expression increased
proportionally with CATT length. Mif lung-Tg2.1 mice exhibited more pulmonary
granulomas than WT mice, which in turn showed more granulomas than Mif-KO mice. A
significantly higher percentage of Mif lung-Tg2.1 mice, compared to Mif-KO or WT
mice, died when injected with Candida albicans beta-glucan, and treatment of
these mice with an anti-MIF monoclonal antibody protected against a lethal
outcome. Levels of MIF-dependent neutrophil/macrophage chemokines were elevated
in the bronchoalveolar lavage fluid or plasma of Mif lung-Tg2.1 mice. CONCLUSION:
Patients with GPA have an increased frequency of high MIF expression CATT
alleles. Higher Mif expression increases the incidence of mortality and pulmonary
granulomas in Mif lung-Tg2.1 mice, while anti-MIF treatment protects these mice
against death. Blockade of MIF in high genotypic MIF expressers may therefore
offer a selective pharmacologic therapy for GPA.
PMID- 29953755
TI - FIGHTING THE OPIOID CRISIS FROM THE FRONT LINE. How EMS can share data and
partner with public health to help combat the overdose epidemic.
PMID- 29953756
TI - It Takes a Team of Teams to Transform Healthare. Northwell Health's integrated
EMS revolution.
PMID- 29953757
TI - Medical Control: Colleagues in Patient Care. Its mission should be not only
consultative but collaborative.
PMID- 29953758
TI - Radiation Injury, Burns and Illness: A Review of Best Practices. Your approach
should include identifying sources, determining exposure and managing resources.
PMID- 29953759
TI - Strategies for Longevity in EMS. A dozen ways to ensure a long and rewarding EMS
career.
PMID- 29953760
TI - READY FOR THE HEAT: Training Inside the Hot Zone.
PMID- 29953761
TI - BODY ARMOR INJURIES: What You Heed to Know. Know the capabilities and limitations
of armor, and the mechanisms of injury you may encounter.
PMID- 29953762
TI - An Introduction to K9 Tactical Emergency Casualty Care. New initiative blends
evidence-based medicine and user experience for high-threat veterinary trauma
care recommendations.
PMID- 29953763
TI - Pony Up. Years later, the lessons of a mentor still prove their value.
PMID- 29953764
TI - For Getting Better, Every Metric Matters. EMS is a rich source of data that can
help you improve your organization's efficiency.
PMID- 29953765
TI - Patient Handoffs. Are EMS providers including all key information when they turn
patient care over?
PMID- 29953766
TI - The Worst-Case Bariatrik Patient. When a homebound, germ-phobic patient needed
care, a system found itself unprepared.
PMID- 29953767
TI - How Care Collaboration Is Improving Patient Outcomes. In South Florida,
paramedics serve as the "eyes, ears and hands" of vulnerable patients'
physicians.
PMID- 29953768
TI - How a Novel Disease Threat Brought EMS and Public Health Together. In Washington,
Ebola efforts helped players and systems improve cooperation and collaboration.
PMID- 29953769
TI - EMS WORLD ROUNDTABLE: Ambulane Safety and Innovation. What's new and what's
concerning to experts in EMS transportation?
PMID- 29953770
TI - Kansas Agency to Field a Low-Top Ambulane. Butler County EMS is bringing a
European design to the U.S.
PMID- 29953771
TI - Virginia Brings Standards to Remounts. State law outlining requirements for
ground ambulances doesn't exempt them, leaders say.
PMID- 29953772
TI - Understanding the Gas Exchange Process. The body's use of oxygen and creation of
carbon dioxide requires a highly efficient absorption/elimination and transport
system.
PMID- 29953773
TI - When 'Just Ask' Doesn't Work. Consider the when and why along with the what.
PMID- 29953774
TI - Multidisciplinary management of advanced ovarian cancer for an optimal
therapeutic strategy.
AB - The management of advanced ovarian cancer generally requires specialist
multidisciplinary teamwork to achieve optimum outcomes. Preoperative computed
tomography scans are the imaging modality of choice in determining the extent of
disease and aiding in surgical planning. Histological classification is crucial
to define various subtypes with their different behaviour and prognosis and to
plan the best therapeutic strategy. Pathological prognostic factors, such as
histological type, degree of differentiation, and FIGO stage must be described.
To determine the ability to optimally cytoreduce advanced ovarian cancer, an
experienced gynaecological oncologist needs to explore the entire upper abdomen
and the pelvic and para-aortic lymph node regions to define the peritoneal cancer
index (PCI). The final assessment is the completeness of cytoreduction (CC) score
which is important in predicting prognosis and decision of post-surgical surgery.
Ovarian cancer is the leading cause of death from gynaecologic cancers. Initial
management is best provided by a specialist multidisciplinary team, including a
radiologist, a pathologist, a gynaecologic oncologist, and a medical oncologist.
PMID- 29953775
TI - Role of cancer stem cells and microRNA in resistance to chemotherapy in patients
with ovarian cancer.
AB - Despite the introduction of "the golden standard" in chemotherapy for ovarian
cancer (taxanes/platinum), a relapse of the disease is noted in 80% of women
treated in this manner. Studies on ovarian cancer stem cells (CSCs) and attempts
at treatment using salinomycin, isolated from Streptonzyces albus and endotoxin
of Clostridium peifringens, are promising, in particular because CSC markers have
been identified. Resistence of ovarian cancer cells to paclitaxel and cisplatin
is associated with a reduced expression of miR-30c, miR-130, and miR335, which
results in activation of M-CSF, the known factor of resistance to cytostatic
drugs. In clear cell ovarian cancer, a reduced expression of miR-449 was
detected, which may lead to overexpression of MET phenotype, typical for
chemoresistant ovarian cancer. MicroRNAs remain in investigations, but their
involvement in the control of genes linked to the development of the cancer and
its progression seems to offer the promise of a targeted therapy.
PMID- 29953776
TI - Automated breast volume scanner (ABVS) in breast cancer - a review.
AB - The early detection of breast cancer is essential for its timely diagnosis and
treatment. Many imaging modalities are continually being developed to screen and
diagnose breast cancer at an early stage. Especially, ultrasound (US) is one of
useful diagnostic tools to dis- tinguish benign from malignant masses of the
breast. However, the US image has some limitations, such as low resolution and
low con- trast, speckle noise, and blurry edges between various organs. Recent
technological advancements in the area resulted in development of automated
breast volume scanner (ABVS) that could increase the diagnostic confidence for a
physician and provide a possible solution to improve the positive predictive
value of breast biopsy. The purpose of the present review article was to explore
the advantages and technical advancements of ABVS for diagnosing breast cancer
patients.
PMID- 29953777
TI - Correlation between the body mass index of patients with breast cancer before and
after chemotherapy.
AB - The objective of this work was to show how the influence of the microenvironment
in tumor cells and consequently the onset and tumor progression is becoming
increasingly more evident. Cancer is the second leading cause of death in the
developed world, surpassed only by heart disease and obesity, and is increasingly
recognised as an oncogenic factor in the genesis of this tumor. Inflammatory me-
diators related to obesity are suspected to play a role in oncogenic modification
of substrates metabolism of nutrients, most patients diagnosed with breast cancer
underwent chemotherapy treatment, and this may be an aggravating factor of
obesity. The authors selected 49 patients with previous diagnosis of breast
cancer who had undergone chemotherapy and evaluated data regarding body mass
index (BMI) before and after chemotherapy. They observed that there was
statistical difference of BMI of patients before and after chemotherapy with p =
0.03. Comparing the groups, a statistical difference was found between overweight
and obesity grade II and overweight and obesity grade III. Patients with a
diagnosis of breast cancer usually showed on average a BMI 27.84, worsening after
chemotherapy to 28.64. These findings can help to accelerate the division and
cell reproduction, because obesity is a risk factor for breast cancer, and weight
gain seems to be a major factor after treatment and may influence the prognosis
of these women.
PMID- 29953778
TI - Expression of IncRNA UCA1 in ovarian cancer and its clinical significance.
AB - OBJECTIVES: To explore the expression and clinical significance of IncRNA-UCA1 in
ovarian cancer. MATERIALS AND METHODS: The ex- pression of IncRNA-UCA1 in 26
ovarian cancer tissue and 16 normal and benign ovarian tissue were detected using
qRT-PCR method, and the correlation of expression level with clinicopathological
features were analyzed. RESULTS: Higher lncRNA-UCA1 expression level were
detected in ovarian cancer tissue than those in normal ovarian tissue (p < 0.05).
There were significant correlations between higher expression of IncRNA-UCA1 with
tumor staging (p = 0.000), histological grades (p = 0.000), peritoneal effusion
(p = 0.001), and lymph node metastasis (p = 0.000), but not with age. CONCLUSION:
IncRNA-UCA1 may play a vital role in the metastasis of ovarian cancer and it is
expected to be a potential novel biomarker and therapeutic target of ovarian
cancer.
PMID- 29953779
TI - Complications following type 3 excision by needle excision of the transformation
zone: a case series report.
AB - OBJECTIVE: To determine short-term complications and related risk factors
following needle excision of the transformation zone (NETZ). MATERIALS AND
METHODS: A case series of 105 women with NETZ for cervical pathology between 2006
2013 in a single center. RESULTS: The overall complication rate was 22.9%. Heavy
primary bleeding occurred in 12.4% of cases (<500 ml), secondary hemorrhage 7.6%,
emergency hysterectomy 1.9%, and cervical stenosis 2.9%. Where excision depth was
> 20 mm, this was a non-significant increase in the risk of hemorrhage, but a
significant reduction in the risk of a subsequent hysterectomy (p = 0.035).
CONCLUSION: NETZ is associated with a number of complications and recognition of
risk factors should be considered when planning type 3 excisional procedures and
counseling women.
PMID- 29953780
TI - Defective expression of polarity protein Par3 promotes cervical tumorigenesis and
metastasis.
AB - OBJECTIVES: The aim of this study was to investigate whether the partition
defective 3 protein (Par3) regulates cervical carcinoma growth and metastasis.
MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to analyze the
expression of Par3 protein in samples from 89 cervical squamous cell carcinoma
(CSCC) patients among Uyghur women. The specific short hairpin (shRNA) vector as
well as eu- karyotic expression vector of PARD3 was transfected into SiHa cell
lines. The variation of migration and invasion after transfection was determined
using Transwell assays, cell cycle, and apoptosis were assayed by flow cytometry,
respectively. RESULTS: The incidence of CSCC was associated with reduced
expression of Par3. Downregulation of Par3 was significantly associated with more
advanced tumors (i.e., higher histological grade, lymph node involvement, and
higher tumor stages) (p < 0.05 for all). Lost expression of Par3 promotes prolif-
eration, inhibits apoptosis, and enhances migration and invasion. Loss of Par3
induces MMP9 expression and epithelial to mesenchymal transition (EMT) related
genes (N-cadherin, E-cadherin, and beta-catenin) expression changed in SiHa
cells. CONCLUSIONS: The reduced Par3 expression in cervical cancer indicates
tumor-suppressive properties of Par3 that may be a marker of poor prognosis in
cervical cancer patients, and the molecular determinants of epithelial polarity
which have tumorigenesis enhancing impact, might through EMT.
PMID- 29953781
TI - Immunohistochemical c-kit expression in uterine serous carcinoma tissue.
AB - AIM: Uterine serous carcinoma (USC) is an aggressive tumor that represents only
10% of endometrial cancer cases but accounts for a disproportionate number of
deaths due to uterine cancer. Advances in the development of specific c-kit
receptor-targeted drugs have promoted its potential therapeutic application as a
target in tumor-related diseases. The aim of the present study was to evaluate
imunohistochemical expression of c-kit in USC tissue in order to assess whether
positive cases can be candidates for targeted therapy. MATERIALS AND METHODS: C
kit expression assessment by immunohistochemistry was performed on deparaffinized
sections of paraffin-embedded tissue blocks of confirmed consecutive available
USC uterine specimens of patients diagnosed from 2000 to 2014. Sections of
gastrointestinal stromal tumor (GIST) tissue known to contain c-kit served as
positive controls. RESULTS: Immunohisto- chemical c-kit staining was not observed
in any of 31 USC tissue samples examined. Intense staining was observed in the
sections of GIST tissue. CONCLUSION: The present results may indicate that
primary USC is not a candidate for c-kit targeted therapy.
PMID- 29953782
TI - Application of combined intraperitoneal and intravenous neoadjuvant chemotherapy
in senile patients with advanced ovarian cancer and massive ascites.
AB - OBJECTIVE: The aim of this study was to explore the effects of neoadjuvant
chemotherapy in senile patients with advanced ovarian can- cer and ascites.
MATERIALS AND METHODS: One hundred eight senile patients with advanced ovarian
cancer and ascites were randomly di- vided into two groups: experimental and
control groups. Patients in the experimental group were treated with two courses
of intraperitoneal combined with intravenous neoadjuvant chemotherapy, followed
by cytoreductive surgery, and six courses of intravenous chemotherapy, while the
patients in the control group only received cytoreductive surgery and six to
eight courses of intravenous chemotherapy. RESULTS: The operation duration, blood
loss, ideal success rate of cytoreductive surgery, and prognosis of the two
groups were then compared. Thirty-eight patients in the experimental group
successfully received cytoreductive surgery, accounting for 74.14%, while only 23
patients in the control group received cytoreductive surgery successfully,
accounting for 46%, showing signifinificantly less than those in the control
group (p < 0.001). However, the median survival and the median progression-free
survival showed no statistical difference between the two groups (p > 0.05).
CONCLUSIONS: Neoadjuvant chemotherapy can obviously shorten the operation
duration, reduce the intraoperative blood loss, and improve the ideal success
rate of cytoreductive surgery, but does not obviously improve the prognosis.
PMID- 29953783
TI - Ovarian Sertoli-Leydig cell tumors: a single institution experience and review of
the literature.
AB - : Purpose ofinvestigation: Sertoli-Leydig cell tumors (SLCTs) of the ovary are
rare, usually presenting as virilization in women in their second to third decade
of life. Less than 10% of patients are older than age 50. The authors present a
series of cases of SCLT managed at their institution. MATERIALS AND METHODS: A
retrospective review was performed of all cases of ovarian SLCT diagnosed at a
tertiary care institution between 1990-2014. Demographic data, clinical
presentation, pathological findings, and treatment modalities were col- lected.
RESULTS: Of the 16 patients diagnosed with SCLT over a 24-year period, nine
patients (56%) were postmenopausal at the time of diagnosis, with a median age of
52.5 years (IQR = 39.7 years). These nine patients had a median interval of 14.7
years (IQR = 15) since the onset of menopause. Hyperandrogenism was a presenting
feature in only five of 16 (31%) [median age of 49 (IQR= 26.5)] whereas
postmenopausal bleeding was noted in two of 16 (12%). At diagnosis, tumor grade
varied from well- to poorly-differentiated lesions, and eight patients (15%)
received adjuvant chemotherapy. Disease-free survival over a median follow up of
31.5 months (IQR = 73.5 months) was 100% without recurrence. CONCLUSION: The
present patient population was noticeably older than what has been described in
literature, with the majority being postmenopausal. To the authors' knowledge,
this is the largest series of postmenopausal patients with SLCT. Hyperandrogenism
was evident in only a small sub-group. While the definitive management of SLCT
remains controversial and varied, prognosis and risk of recurrence are
reassuring.
PMID- 29953784
TI - Direct uterine sampling using the SAP-l sampler device to detect endometrial
lesions during histopathological examination.
AB - AIMS: To evaluate the sampling adequacy and diagnostic accuracy of the
endometrial SAP-l sampling device in detecting endometrial lesions based on
histopathological examination. MATERIALS AND METHODS: In total, 182 patients who
required an endometrial biopsy were enrolled in this study. All of the patients
underwent endometrial biopsies with the SAP-l sampler prior to hysteroscopy
(169/182) or dilatation and curettage (D&C) (13/182). Endometrial tissues were
obtained at biopsy for histopathological examination. RESULTS: Ad- equate
endometrial specimens were obtained in 148 of 182 patients (81.32%). Menopause (p
= 0.000), endometrial thickness (p = 0.004), and the types of endometrial
diseases (p = 0.009) differed significantly between the two groups. Among the 169
patients who underwent hysteroscopy, sampling scratches were observed in the
uterine cavity in 147 cases (86.98%). Compared to traditional methods, such as
hysteroscopy and D&C, the sampling diagnostic sensitivity, specificity, and
positive and negative predictive values were 82.35%, 100%, 100% , and 97.76% for
endometrial carcinoma (n=17) and 37.5%, 100%, 100% and 97.76% for endometrial
atypical hyperplasia (n=8), respectively. Those that were misdiagnosed occurred
because the lesions were focal or localized in a small part of the uterine
cavity. The sampling diagnostic sensitivity for polyps (n=32) was 12.5%. Two
patients with submucosal leiomyoma went undiagnosed based on the sample
specimens. CONCLUSION: Endometrial sampling using the SAP-l sampler is a
minimally invasive altemative technique for obtaining adequate endometrial
specimens for histopathological examination. The SAP-l sampler was useful in
detecting endometrial carcinoma and atypical hyperplasia cases that were not
highly suspected to be localized; however, this method was not useful in
detecting endometrial polyps and submucosal leiomyomas.
PMID- 29953785
TI - Central nervous system metastatic epithelial ovarian cancer. Clinical parameters
and prognostic factors: a multicenter study of Anatolian Society of Medical
Oncology.
AB - : Central nervous system (CNS) metastasis is a rare event in the course of late
stage epithelial ovarian cancer (EOC); however its incidence is increasing in
parallel with prolonged survival of patients. OBJECTIVE: The authors assessed the
clinical parameters and potential prognostic features in patients with CNS
metastatic disease. MATERIALS AND METHODS: Clinical data of the 33 patients from
the participating centers were retrospectively collected and analyzed. Median age
at the time of CNS metastasis was 57 years. Median time from the diagnosis of
primary EOC until CNS metastatic disease was 22 months. Nearly half (45.5%) of
the patients had single CNS metastatic lesions and all patients in the study
group except two received radiotherapy as palliative treatment. Median overall
survival (OS) from the time of CNS metastasis was 15 months (0-66). At univariate
analysis only number of brain metastatic lesions (p = 0.001) and presence of
extracranial disease (p = 0.004) were strongly associated with OS whereas
multimodal treatment, size of metastatic lesions, platinum sensitivity, age,
grade, and disease stage at presentation were not. Development of CNS metastasis
carries a poor prognosis, however patients with single metastatic lesions and
only intracranial metastatic disease can have prolonged survival after
appropriate palliative management of their disease.
PMID- 29953786
TI - Lymph node involvement in clinically apparent early ovarian cancer: a prospective
study.
AB - PURPOSE: The objective of this study was to identify the lymph node involvement
in apparently early ovarian cancer (OC) Materials and Methods: Patients with
clinically apparent early OC who underwent staging surgery between August 2012
and August 2015 were prospectively identified. Patients' characteristics and
tumor histopathology were evaluated. RESULTS: Twenty consecutive patients were
operated for grossly apparent early ovarian carcinoma. All patients were
surgically staged and underwent a systematic pelvic and para- aortic
lymphadenectomy. There were eight patients (40%) with lymph node involvement. One
of the eight lymph node metastasis was solely in para-aortic node, three patients
had both positive-pelvic and aortic nodes, and the other metastasis was in
ipsilateral pelvic lymph node. Positive lymph node involvement was significantly
higher among patients with poorly differentiated tumor grade (62.5%) (p = 0.02).
CONCLUSION: All patients diagnosed with early OC macroscopically confined to the
ovaries should be considered for compre- hensive staging surgery including pelvic
and para-aortic lymphadenectomy.
PMID- 29953787
TI - Inhibitory effects of miR-101 overexpression on cervical cancer SiHa cells.
AB - PURPOSE OF INVESTIGATION: microRNAs (miRNAs), which can regulate cell biological
behaviors such as proliferation and apoptosis as oncogenes or anti-oncogenes, are
closely associated with cancer onset and progression. The aim of this study was
to detect the expres- sion changes of miR-101 in cervical cancer tissues and the
effects on the biological functions of cervical cancer SiHa cells. MATERIALS AND
METHODS: Through transient transfection of SiHa cells with mature miR-101
sequences, the effects on apoptosis, proliferation, and cell cycle were evaluated
by real-time PCR, CCK-8 assay, and flow cytometry. RESULTS: Significantly less
miR-101 was expressed in cervical cancer tissues than that in normal cervical
tissues. miR-101 was overexpressed in SiHa cells through transient transfection
of miR-101 mimics. CCK-8 assay and flow cytometry showed that miR-101
overexpression significantly inhibited cell proliferation, pro- moted apoptosis,
and arrested them in the G(l)/S phase. Real-time PCR exhibited that Mcl-i and c
Fos mRNA expressions significantly decreased. CONCLUSION: miR-101 significantly
reduced the viability of SiHa cells as a potential anti-oncogene.
PMID- 29953788
TI - Prevalence of high risk human papillomavirus (HPV) infection and abnormal
cervical cytology and knowledge about HPV vaccine in Eastern Turkey.
AB - PURPOSE OF INVESTIGATION: The aim of the present study was to gather data on the
high risk human papillomavirus (HPV) frequency and the distribution of HIPV types
in Eastern Turkey in relation to cervical cytology and to assess the knowledge
about cervical cancer, HPV, and vaccination. MATERIALS AND METHODS: The study
population included 1,000 women aged between 20-65 years who attended the
outpatients clinics of Department of Obstetrics and Gynecology of the Medical
School of Yuzuncu Yil University Hospital. RESULTS: The overall prevalence of
high risk HPV-DNA was 2.8 %. Abnormal cytology was observed in 12.9% of the
cases. Abnormal cytology consisted of cervical cancer: 0.1%, LSIL: 1.6%, HSIL:
0.5%, ASC-H: 2.1%, atypical glandular cells: 0.4%, and ASCUS: 8.3 %. CONCLUSION:
The prevalence of HPV was low in Eastern Turkey and the most common HPV types are
similar to the literature. However, the prevalence of HPV infection is a growing
problem worldwide and the awareness of the women in the region is limited.
PMID- 29953789
TI - Overexpressed LEDGF is a novel biomarker of poor prognosis in patients with
cervical cancer.
AB - Lens epithelium-derived growth factor (LEDFG) can prevent cells apoptosis by
activating stress proteins and anti-apoptotic protein, which are involved in the
development of a variety of malignancies as some studies have shown. However,
little is known about the role of LEDGF in cervical cancer. In this study, the
authors collected 95 cases of the cervical cancer tissue samples and its matching
tissue adjacent to carcinoma diagnosed by the Department of Pathology. mRNA
expression of LEDFG in randomly selected 20 cervical can- cer tissues and 20
adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR).
LEDFG protein expression in randomly selected 20 cervical cancer tissues and 20
adjacent normal tissues was detected by immunohistochemistry (IHC) and Western
Blot (WB). All patients were followed up for about three years. The authors found
that both mRNA and protein expression level of LEDFG was significantly higher in
cancer tissues compared with normal controls (p < 0.05) and this overexpression
was significantly correlated with the histologic grade, the immersion depth of
interstitial, the invasion of vessel, and lymph node status of cervical cancer.
Furthermore, the three-year survival rate of 34 patients with LEDGF positive
expression having a survival rate of three years was 57.6%. The survival rate of
three years with negative expression was 91.7%. The survival rate of patients
with LEDGF positive ex- pression was significantly lower than those of the
negative expression (p <0.01). In conclusion, the present results suggest that
LEDFG expression is an independent prognostic biomarker for cervical cancer.
PMID- 29953790
TI - Forkhead box protein 3 (FoxP3) mRNA as a diagnostic marker in ovarian tumors: a
pilot study.
AB - PURPOSE: To assess the diagnostic performance of forkhead box protein 3 (FoxP3)
mRNA in ovarian tumors. MATERIALS AND METHODS: Using quantitative real time
reverse transcription PCR (q-RT-PCR), FoxP3 mRNA level was measured in fresh
frozen ovarian tumors and its diagnostic performance was compared to those of
preoperative serum CA 125 and risk of malignancy index (RMI). RESULTS: FoxP3 mRNA
was differentially expressed in the malignant (n = 25) and benign (n = 25)
groups, yet without statistically significant differences; positivity rate: 15/25
vs. 10/25; p = 0.157, median: 0.429 vs. 0.046; p = 0.684, and mean +/- SD: 73.75
+/- 234.68 vs. 247.09 +/- 792.17; p = 0.30 1. Although it showed much less
diagnostic performance (AUC: 0.534), FoxP3 mRNA enhanced the diagnostic
sensitivity and specificity of both CA125 and RMI (96% and 100%, for both).
CONCLUSION: FoxP3 mRNA may not be good diagnostic marker in ovarian tumors;
however it may prove valuable in defining underlying tumor molecular signature.
PMID- 29953791
TI - Clinical evaluation of MRI in the differential diagnosis between benign and
malignant ovarian tumors.
AB - Ovarian tumors present a special diagnostic challenge when imaging findings
cannot be categorized into benign or malignant pathology. Magnetic resonance
imaging (MRI) is currently used to evaluate ovarian tumors. The aim of this study
was to evaluate the diagnostic performance of MRI in patients with benign or
malignant ovarian tumors and enhance its diagnostic accuracy. The MRI findings of
48 cases of ovarian tumors, which were confirmed by surgery or pathology from
September 2009 to July 2011, were analyzed ret- rospectively. Ti-, T2-, and fat
suppressed T2-weighted sequences were performed and dynamic contrast-enhanced Tl
weighted gradient-echo images were performed after IV injection of Gd-DTPA by 1.5
T unit. The ovarian tumors were examined for several features including size,
bilaterality, shape, content (solid-cystic), signal intensity, and enhancement.
Secondary signs such as ascites, peritoneal disease, and lymphadenopathy were
noted. The imaging features with the surgical and pathologic findings were
compared and the MRI features of benign and malignant ovarian tumors were
compared and summarized. MRI features of 33 cases of malignant ovarian tumors
were cystic-solid or solid masses, with irregular wall, and intense enhancement.
MRI features of 15 cases of benign ovarian tumors were cystic masses, with
regular wall, and not or slightly enhanced. The differences of bilaterality,
shape, content (solid-cystic), signal intensity, and enhancement between benign
and malignant ovarian tumors were statistically significant (p < 0.01). The data
demonstrate MRI features may help differentiate benign ovarian tumors from
malignant ovarian tumors.
PMID- 29953792
TI - Anatomical variations of the obturator veins and their surgical implications.
AB - PURPOSE OF INVESTIGATION: The obturator veins and their network contribute to
major bleeding complications during gynaecologic surgery. MATERIALS AND METHODS:
The anatomical variations of the obturator veins were studied on 106 patients in
which a thorough bilateral pelvic lymphadenectomy was performed. RESULTS:
Symmetrical drainage on right and left sides was found in 75 cases: only in
internal iliac vein in 32 cases, both in external iliac vein and internal in 41
cases, and only in external in two cases (so called "pubic vein"). In 31
procedures, asymmetric drainage was found between the two sides: one side in
internal, the other side both in internal and external in 25 patients; in three
patients, in external on one side and in both internal and external on the other;
and in external on one side and in internal on the other side in one patient.
CONCLUSIONS: Anatomical variations of the obturator veins appear quite often.
PMID- 29953794
TI - Suppressing stathmin-l can inhibit chkl protein expression and reduce the
invasion and tumorigenicity of cervical cancer cells.
AB - The purpose of this study was to evaluate the effects of stathmin-l on chkl
protein expression in cervical cancer cells and the influ- ences on the cells'
invasion and tumorigenicity. Suppressed stathmin-l expression in Hela cells and
C33A cells by lentiviral vector were utilized. Real time PCR and Western blot
were used to examine the expression of chkl. Cell proliferation and invasion were
stud- ied using MTT assays and transwell migration assays.The differences of
tumorigenicity in vivo were explored using xenograft experi- ments. In addition,
stathmin-l expressions in 24 cervical cancer patients were studied without
regional lymph nodes metastasis and 16 metastatic patients by
immunohistochemistry assays and real time PCR. This study found downregulating
stathmin-l reduced chkl ex- pressions and the proliferation and invasion in
cervical cancer cells and reduced the tumorigenicity of tumor cells.
PMID- 29953793
TI - Role and timing of second-line therapies for patients with recurrent platinum
resistant ovarian epithelial cancer.
AB - OBJECTIVE: To explore the regimens and prognoses of second-line therapies for
recurrent platinum-resistant ovarian epithelial cancer (OEC). MATERIALS AND
METHODS: The clinical profiles and second-line regimens were retrospectively
analyzed for 65 recurrent platinum-resistant OEC patients treated at Zhejiang
Provincial Tumor Hospital during January 2003 to January 2013. In conjunction
with literature reviews, the second-line therapies for platinum-resistant
recurrent OEC were discussed. RESULTS: Their average age was 55.2 years. The
stages were I (n=4), II (n=3), III (n=45), and IV (n=13). The predominant type
was serous adenocarcinoma (n=47, 72.3%). Chemotherapy was refused (n=14) and
resistant (n=5 1). One case was lost to follow-up and another three withdrew
early. An average of four chemotherapeutic courses were offered in 61 cases.
Among them, five cases selected chemotherapy after a second operation. The
average therapy-free interval (TFI) was 3.5 months. The efficacies were evaluated
for 61 cases. CR (n=5) and partial remission (PR, n=22). The overall survival
(OS) rate was 43.6% and average progression-free survival (PFS) was 15.44 months.
CONCLUSION: The efficacy of second-line therapy for recurrent platinum-resistant
OEC is rather poor and the feasibility and efficacy of second operation are to be
further explored.
PMID- 29953795
TI - Hypoxia induces autophagy in PA-l ovarian teratoma cells and resistance to growth
inhibition and apoptosis by chemotherapeutic agent cis-diamminedichloroplatinum.
AB - Pathological hypoxia exists in solid tumors and it creates a microenvironment for
tumor cells which has a critical and complicated implication for cancer. Hypoxia
can also activate autophagy which plays a dual role in cancer. In this study the
authors analyzed the effect of hypoxia, the autophagy inhibitor 3-methyladenine
(3-MA), cis-diamminedichloroplatinum (CDDP, cisplatin), and any combination of
them on PA-l cells (a human ovarian cancer cell line) with a series of assays,
focusing on autophagy induction, cell growth inhibition, and cell death by CDDP.
CDDP caused apoptosis in normoxic PA-l cells and autophagy upon hypoxia treatment
decreased apoptosis induction in hypoxic cells by CDDP, which has implications in
cancer chemotherapy resistance.
PMID- 29953796
TI - The role of oxidative stress in premalignant lesions.
AB - PURPOSE OF INVESTIGATION: The authors aimed to evaluate serum total oxidant
status (TOS), total antioxidant status (TAS), and oxida- tive stress index (OSI)
in women with abnormal cervical cytology, to determine the association between
serum oxidant and antioxidant status of these women, and the progression of
abnormal cervical cytology. MATERIALS AND METHODS: A total of 75 women enrolled
in the study: 20 women with a determination of atypical squamous cells of
undetermined significance (ASCUS), 20 women with low squamous intraepithelial
lesions (LSIL), 15 women with high squamous intraepithelial lesions (HSIL) and 20
healthy controls. Serum TOS and TAS were determined and OSI was calculated as the
indicator of degree of oxidative stress. RESULTS: Serum TOS levels and OSI were
highest in the HSIL group and there was a trend toward increasing serum TOS
levels and OSI from ASCUS to HSIL group. CONCLUSION: The authors demonstrated
that increased oxidative stress with altered antioxidant level is associated with
abnormal cervical cytology. Serum oxidant and antioxidant status may provide
guidance as a simple and cost-effective method for follow-up, treatment, and
recommendation in all stages of lesions.
PMID- 29953797
TI - Two unusual cases: vulvar lipoma - description of the largest case in literature.
Developing myoma with the longest pedicle.
AB - The authors present two cases of benign tumors one located on the outer surface
of the vulva, and the second extending beyond the vagina. The first, originating
from the right pudendal lip, a lipoma measuring 23 cm in greatest diameter,
weighing 6.6 kg, and the second a pedunculated, uterine smooth muscle myoma with
a pedicle of 6.5 cm, maximum diameter 18 cm, weight 700 grams, which caused
significant metroptosis. Operative procedures in each case were free of
complications.
PMID- 29953798
TI - Rapidly progressing central-type primitive neuroectodermal tumor of the ovary: a
case report.
AB - Primitive neuroectodermal tumors (PNET) belong to a group of highly malignant
tumors comprised of small round cells of neu- roectodermal origin. These tumors
can be either of peripheral-type (Ewing family tumors/PNET) or central-type. A
number of case re- ports have described PNET involving the gynecologic organs and
the prognosis is generally poor. The authors describe the case of a 53-year-old
woman with a rapidly progressing central-type PNET of the ovary.
PMID- 29953799
TI - High cellularity and mitotic activity in a primary ovarian fibro-thecomatous
tumor of a young patient: a diagnostic and clinical challenge.
AB - : Purpose ofInvestigation: Solid ovarian tumors represent a clinical challenge,
in particular in case of young patients who require a fertility sparing
treatment. The authors report a case of hypercellular mitotically active ovarian
fibrothecoma in a very young woman, successfully treated with a fertility sparing
surgery. MATERIALS AND METHODS: A 21-year-old nulliparous woman presented at the
present hospital with a 14-cm right ovarian mass, consisting of solid and pseudo
cystic components. There was neither an elevation of tumor markers nor evidence
of metastatic disease. A laparotomic right salpingo-oophorectomy was performed.
Uterus and left adnexa were preserved. RESULTS: The neoplasm consisted of a
prevalent population of spindle-shaped elements and of a minor component of cells
with wider cytoplasms, attributable to a thecomatous differentiation. The mitotic
activity was focally elevated. Cytological atypia was mild to focally moderate.
Clear areas of coagulative necrosis were not observed. At present 48 months after
surgery, the patient is alive with no evidence of recurrence. CONCLUSIONS: The
authors reported the lesion as a hypercellular and mitotically active
fibrothecoma. The uneventful follow-up confirms the low malignant potential of
the lesion. Caution is required reporting hypercellular stromal ovarian tu- mors,
in order to avoid overdiagnosis and overtreatment, particularly in young
patients.
PMID- 29953800
TI - Cloacogenic adenocarcinoma of the vulva: one new case and literature review.
AB - Primary adenocarcinoma of the vulva is uncommon, and cloacogenic adenocarcinoma
of the vulva is extremely rare. Here the authors report a vulvar neoplasm,
arising in continuity with the epidermis, characterized by villoglandular
architecture, and mucinous-type ep- ithelium with intestinal differentiation
(goblet cells). Histochemistry, immunohistochemistry, and gene mutation analysis
revealed a colon-like pattern, except for CK7 expression. Extensive workup failed
to reveal other primary cancers. In order to provide a much bet- ter experience
for diagnosis, the authors compared the previously published cases with the
present case regarding clinical presentation and histopathologic aspect. They
believe that the notion of the tumor arising from cloacal remnants is a more
acceptable viewpoint, and its behavior is mostly indolent. In the present case, a
wide local excision was sufficient for radical cure.
PMID- 29953801
TI - Endometriotic lesions mimicking advanced ovarian cancer - A case report and a
review of the literature.
AB - BACKGROUND: Approximately 2-5% of women affected by endometriosis are
postmenopausal. The disease may simulate various malignancies. A case of
endometriosis in a postmenopausal woman, spreading similarly to ovarian cancer,
is reported. A broad review of existing literature on postmenopausal
endometriosis, endometriosis involving the urinary tract, and the links between
endometriosis and cancer are also presented. CASE DESCRIPTION: A 51-year-old
woman was diagnosed with a pelvic mass. She complained of pain in the lower
abdomen that began three weeks prior, and had no history of dysmenorrhea, acyclic
pelvic pain, or infertility. CT scan revealed a solid and cystic tumor in the
region of the right adnexa, infiltrating the surrounding tissues, with possible
infiltration of the urinary bladder, as well as soft-tissue lesions of the small
intestinal mesentery. Bilateral hydronephrosis and distension of the ureters were
also present. A malignant neoplasm of the ovary or the corpus uteri was
suspected. Total abdominal hysterectomy and appendectomy were performed. A
superficial infiltration of the urinary bladder was also excised. The pathology
report revealed endometriotic foci in the tumor and in the bladder infiltration,
as well as an endometriotic cyst in the right ovary. Two years postoperatively
the patient is disease-free and in good condition. CONCLUSIONS: Clinicians should
remain conscious of the possibility of endometriosis mimicking advanced ovarian
cancer and infiltrating the peritoneum and internal organs of the abdominal
cavity, including the urinary tract. Imaging techniques, including CT and MRI,
are not always effective in establishing the correct diagnosis preoperatively.
PMID- 29953802
TI - Vulvar and gastric involvement in plasmablastic lymphoma.
AB - Plasmablastic lymphoma is highly malignant and invasive. It is most commonly
found in gastrointestinal tract and is strongly asso- ciated with human
immunodeficiency virus (HIV). The authors report a case of a 37-year-old HIV
positive African American woman with a vulvar mass diagnosed as plasmablastic
lymphoma. Involvement of the upper gastrointestinal tract had been detected by
endoscopic biopsy, suggesting that any patient diagnosed with plasmablastic
lymphoma in unusual locations should be investigated for primary lesions in the
gastrointestinal tract.
PMID- 29953803
TI - Advanced stage yolk sac ovarian tumour: clinical approach with cytoreductive
surgery upfront.
AB - The authors report the case of a 21-year-old woman that presented a Pseudo Meigs'
syndrome, secondary to a pure endodermal sinus tumour (yolk sac tumour). Fine
needle aspiration biopsy was compatible with high-grade carcinoma and the alpha
fetoprotein (alphaFP) was at 13,185 U/ml. Cytoreductive surgery was performed,
followed by bleomycin, etoposide, and cisplatin (BEP) chemotherapy.
PMID- 29953804
TI - Retroperitoneal primitive neuroectodermal tumor (PNET): case report and review of
literature.
AB - Primitive Neuroectodermal tumor belongs to the family of Ewing's tumor and is
characterized by at (11;22) (q24;ql2) or at (21;22) (q22;ql2) translocation.
Retroperitoneal primitive neuroectodermal tumor (PNET) are rare, usually affect
young adults, and are often diagnosed late. There is no specific characteristics
for imaging. The diagnosis is made on histological examination of the surgical
spec- imen or biopsies. Radiotherapy and chemotherapy complete the treatment. The
authors report the case of a 26-year-old patient who only had pelvic discomfort.
Diagnostic laparoscopy showed a retroperitoneal and retrovesical mass of five
centimeters. The patient benefited from adjuvant chemotherapy and radiotherapy.
She is free of disease 30 months after treatment.
PMID- 29953805
TI - Mixed endometrial stromal and smooth muscle tumor of the uterus in a
postmenopausal woman: morphologic and immunohistochemical features.
AB - Mixed endometrial stromal and smooth muscle tumor of the uterus is a rare
occurrence, and it is truly challenging to diagnose or dif- ferentiate
mesenchymal tumors of the uterine corpus, due to their many overlapping features.
In most cases, the gross pathology of mixed endometrial stromal and smooth muscle
tumor differs from that of pure endometrial stromal and pure smooth muscle
tumors. A 59-year-old postmenopausal woman presented with vaginal spotting, low
abdominal pain, and an uterine mass. Subsequent pelvic magnetic resonance imaging
revealed a 4.0x3.8x3.4-cm sized uterine mass with enhancement. The mass showed
restricted diffusion on diffusion-weighted images, and thus, was suspected to be
uterine sarcoma rather than degenerative leiomyoma. Levels of tumor markers, CA
125, CA 19-9, and SCC, were within their normal ranges. The patient underwent
exploratory laparotomy. Morphological and immunohistochemical evaluations were
performed, and a final diagnosis of mixed endometrial stromal and smooth muscle
tumor of the uterus was rendered. Her postoperative course was uneventful, and
aromatase inhibitor adjuvant therapy was administered.
PMID- 29953806
TI - Chemotherapy-induced differentiation to cure botryoid rhabdomyosarcoma: a case
report and review of the literature.
AB - Rhabdomyosarcoma (RMS) occurs rarely in adults and constitutes 2-6% of all
uterine neoplasms. The authors report the case of a 26-year-old woman diagnosed
with botryoid RMS that presented discordant progression results on follow up
imaging and cytodifferentiation on pathologic control. This case showed that
radiological evaluation could be misleading as the tumor demonstrated
chemotherapy-induced differentiation without volume reduction. This case
illustrates the limitations of using the imaging anatomical dimensions of
sarcomas for treatment planning and highlights the potential role of functional
imaging to assess the response to treatment.
PMID- 29953807
TI - Sclerosing stromal tumor of the ovary in a perimenopausal woman: a case report.
AB - Sclerosing stromal tumor (SST) is a rare ovarian neoplasia deriving from the sex
cord stromal tumor, which occurs usually in the sec- ond and third decades of
life. However, the authors report a 46-year old multiparous woman who presented
with a cystic-solid left pelvic mass, a large amount of ascites, and elevated
serum CA-125, all suggesting a malignant tumor. Surgery was performed and final
histopathological diagnosis of the specimen was diagnosed with SST. The authors
herein report an extremely rare case of SST with a cystic-solid pelvic mass and a
large amount of ascites, which is useful to demonstrate the possibility of SST in
multiparous woman.
PMID- 29953809
TI - Discovery of Reversible DNA Methyltransferase and Lysine Methyltransferase G9a
Inhibitors with Antitumoral in Vivo Efficacy.
AB - Using knowledge- and structure-based approaches, we designed and synthesized
reversible chemical probes that simultaneously inhibit the activity of two
epigenetic targets, histone 3 lysine 9 methyltransferase (G9a) and DNA
methyltransferases (DNMT), at nanomolar ranges. Enzymatic competition assays
confirmed our design strategy: substrate competitive inhibitors. Next, an initial
exploration around our hit 11 was pursued to identify an adequate tool compound
for in vivo testing. In vitro treatment of different hematological neoplasia cell
lines led to the identification of molecules with clear antiproliferative
efficacies (GI50 values in the nanomolar range). On the basis of epigenetic
functional cellular responses (levels of lysine 9 methylation and 5
methylcytosine), an acceptable therapeutic window (around 1 log unit) and a
suitable pharmacokinetic profile, 12 was selected for in vivo proof-of-concept (
Nat. Commun. 2017 , 8 , 15424 ). Herein, 12 achieved a significant in vivo
efficacy: 70% overall tumor growth inhibition of a human acute myeloid leukemia
(AML) xenograft in a mouse model.
PMID- 29953810
TI - Perturbatively Selected Configuration-Interaction Wave Functions for Efficient
Geometry Optimization in Quantum Monte Carlo.
AB - We investigate the performance of a class of compact and systematically
improvable Jastrow-Slater wave functions for the efficient and accurate
computation of structural properties, where the determinantal component is
expanded with a perturbatively selected configuration interaction scheme (CIPSI).
We concurrently optimize the molecular ground-state geometry and full wave
function-Jastrow factor, orbitals, and configuration interaction coefficients-in
variational Monte Carlo (VMC) for the prototypical case of 1,3- trans-butadiene,
a small yet theoretically challenging pi-conjugated system. We find that the
CIPSI selection outperforms the conventional scheme of correlating orbitals
within active spaces chosen by chemical intuition: it gives significantly better
variational and diffusion Monte Carlo energies for all but the smallest
expansions, and much smoother convergence of the geometry with the number of
determinants. In particular, the optimal bond lengths and bond-length alternation
of butadiene are converged to better than 1 mA with just a few thousand
determinants, to values very close to the corresponding CCSD(T) results. The
combination of CIPSI expansion and VMC optimization represents an affordable tool
for the determination of accurate ground-state geometries in quantum Monte Carlo.
PMID- 29953808
TI - Exploration of Benzothiazole Rhodacyanines as Allosteric Inhibitors of Protein
Protein Interactions with Heat Shock Protein 70 (Hsp70).
AB - Cancer cells rely on the chaperone heat shock protein 70 (Hsp70) for survival and
proliferation. Recently, benzothiazole rhodacyanines have been shown to bind an
allosteric site on Hsp70, interrupting its binding to nucleotide-exchange factors
(NEFs) and promoting cell death in breast cancer cell lines. However, proof-of
concept molecules, such as JG-98, have relatively modest potency (EC50 ~ 0.7-0.4
MUM) and are rapidly metabolized in animals. Here, we explored this chemical
series through structure- and property-based design of ~300 analogs, showing that
the most potent had >10-fold improved EC50 values (~0.05 to 0.03 MUM) against two
breast cancer cells. Biomarkers and whole genome CRISPRi screens confirmed
members of the Hsp70 family as cellular targets. On the basis of these results,
JG-231 was found to reduce tumor burden in an MDA-MB-231 xenograft model (4
mg/kg, ip). Together, these studies support the hypothesis that Hsp70 may be a
promising target for anticancer therapeutics.
PMID- 29953811
TI - Rapid and Versatile Cell Aggregate Formation Using Lipid-Conjugated Heparin.
AB - Cell aggregates hold significant therapeutic promise for in vitro cell analysis,
ex vivo tissue models, and in vivo cell therapy and tissue engineering.
Traditional methods of making cell aggregates require long incubation times and
can only produce three-dimensional-spheroid-shaped aggregates. We propose a novel
method of making cell aggregates of diverse sizes and shapes using lipid
conjugated heparin. Shaking the cell suspension containing a small amount of
lipid-conjugated heparin for approximately 30 min produced cell aggregates. This
approach can be applied to any cell type, including stem cells, fibroblast cells,
and T lymphocytes. The shape of biocompatible templates could modulate the shape
of cell aggregates. In addition to layered, multicompartmental cell aggregates on
template, template-free, tube-shaped cell aggregates could also be made. The cell
aggregates formed were alive and maintained biological activities.
PMID- 29953812
TI - Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G
Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity.
AB - There is an urgent need for strategies to combat dengue and other emerging viral
infections. We reported that cyclin G-associated kinase (GAK), a cellular
regulator of the clathrin-associated host adaptor proteins AP-1 and AP-2,
regulates intracellular trafficking of multiple unrelated RNA viruses during
early and late stages of the viral lifecycle. We also reported the discovery of
potent, selective GAK inhibitors based on an isothiazolo[4,3- b]pyridine
scaffold, albeit with moderate antiviral activity. Here, we describe our efforts
leading to the discovery of novel isothiazolo[4,3- b]pyridines that maintain high
GAK affinity and selectivity. These compounds demonstrate improved in vitro
activity against dengue virus, including in human primary dendritic cells, and
efficacy against the unrelated Ebola and chikungunya viruses. Moreover,
inhibition of GAK activity was validated as an important mechanism of antiviral
action of these compounds. These findings demonstrate the potential utility of a
GAK-targeted broad-spectrum approach for combating currently untreatable emerging
viral infections.
PMID- 29953813
TI - Three-Dimensional Electrohydrodynamic Printing and Spinning of Flexible Composite
Structures for Oral Multidrug Forms.
AB - A simple method to rapidly customize and to also mass produce oral dosage forms
is arguably a current bottleneck in the development of modern personalized
medicine. Specifically, delayed-release mechanisms with well-controlled dosage
profiles for combinations of traditional Chinese herbal extracts and Western
medications are not well established. Herein, we demonstrate a novel multidrug
loaded membrane sandwich with structures infused with ibuprofen (IBU) and
Ganoderma lucidum polysaccharide (GLP) using three-dimensional
electrohydrodynamic printing and electrospinning techniques. The resulting
flexible membrane consists of microscaled, multilayered cellulose acetate (CA)
membranes loaded with IBU in the shape of either concentric squares or circles,
as the top and bottom layers of a sandwich structure. In between the CA-IBU
layers are randomly electrospun polyvinyl pyrrolidone (PVP) layers loaded with
GLP. The complete fibrous membrane sandwich can be folded and embedded into a 0
size capsule to achieve oral compliance. Simulated in vitro testing of gastric
and intestinal fluids demonstrated a triphasic release profile. There was an
immediate release of GLP after gastric juices dissolved the capsule shell and the
PVP, followed by the short-term release of 60% of the IBU within an hour
afterward, and the remaining IBU was released in a sustained manner following a
Fickian diffusion profile. In summary, this multidrug (both hydrophilic and/or
hydrophobic) oral system with precision-designed structures should enable
personalized therapeutic dosing.
PMID- 29953814
TI - Spatial Distribution of Secondary Organic Aerosol Formation Potential in China
Derived from Speciated Anthropogenic Volatile Organic Compound Emissions.
AB - Fine particulate matter (PM2.5), largely composed of secondary organic aerosol
(SOA), is currently one of the most intractable environmental problems in China.
As crucial precursors for SOA, understanding the formation propensity of various
volatile organic compound (VOC) species and sources is useful for pollution
control. In this work, we estimated the SOA formation potential (SOAP) of
anthropogenic VOC emissions based on an improved speciated VOC emission inventory
and investigated its distribution in China. According to our estimates, toluene
had the largest SOAP, followed by n-dodecane, m-/p-xylene, styrene, n-decane, and
n-undecane, while passenger cars, chemical fiber manufacturing, asphalt paving,
and building coating were the top five SOAP-contributing sources nationwide. The
spatial distribution of SOAP in China shows a distinct pattern of high values in
the southeast and low values in the northwest. Beijing-Tianjin-Hebei and
surroundings, the Yangtze River Delta, Pearl River Delta, and Sichuan-Chongqing
District were found to have the highest SOAP, particularly in urban areas. The
major SOAP-contributing species and sources differed among these regions, which
was attributed to local industrial and energy structures. Our results suggest
that to mitigate PM2.5 pollution in China, more efficient SOAP-based control
measures should be implemented instead of current emissions-based policies, and
VOC control strategies should be adapted to local conditions.
PMID- 29953815
TI - Thermogelling Platform for Baicalin Delivery for Versatile Biomedical
Applications.
AB - Baicalin (BG) is a natural glycoside with several promising therapeutic and
preventive applications. However, its pharmaceutical potential is compromised by
its poor water solubility, complex oral absorption kinetics, and low
bioavailability. In this work, BG was incorporated in a series of chitosan
(Ch)/glycerophosphate (GP)-based thermosensitive hydrogel formulations to improve
its water solubility and control its release profile. Molecular interactions
between BG and GP were investigated using Fourier transform infrared spectroscopy
(FT-IR), and the ability of GP to enhance the water solubility of BG was studied
in different release media. Drug-loaded Ch/GP hydrogels were prepared and
characterized for their gelation time, swelling ratio, and rheological properties
in addition to surface and internal microstructure. Polyethylene glycol (PEG)
6000 and hydroxypropyl methyl cellulose (HPMC) were incorporated in the
formulations at different ratios to study their effect on modulating the sol-gel
behavior and the in vitro drug release. In vivo pharmacokinetic (PK) studies were
carried out using a rabbit model to study the ability of drug-loaded Ch/GP
thermosensitive hydrogels to control the absorption rate and improve the
bioavailability of BG. Results showed that the solubility of BG was enhanced in
the presence of GP, while the incorporation of PEG and/or HPMC had an impact on
gelation time, rheological behavior, and rate of drug release in vitro. PK
results obtained following buccal application of drug-loaded Ch/GP
thermosensitive hydrogels to rabbits showed that the rate of BG absorption was
controlled and the in vivo bioavailability was increased by 330% relative to BG
aqueous oral suspension. The proposed Ch/GP thermosensitive hydrogel is an easily
modifiable delivery platform that is not only capable of improving the solubility
and bioavailability of BG following buccal administration but also can be suited
for various local and injectable therapeutic applications.
PMID- 29953816
TI - Formulation and Molecular Dynamics Simulations of a Fusidic Acid Nanosuspension
for Simultaneously Enhancing Solubility and Antibacterial Activity.
AB - The aim of the present study was to formulate a nanosuspension (FA-NS) of fusidic
acid (FA) to enhance its aqueous solubility and antibacterial activity. The
nanosuspension was characterized using various in vitro, in silico, and in vivo
techniques. The size, polydispersity index, and zeta potential of the optimized
FA-NS were 265 +/- 2.25 nm, 0.158 +/- 0.026, and -16.9 +/- 0.794 mV,
respectively. The molecular dynamics simulation of FA and Poloxamer-188 showed an
interaction and binding energy of -74.42 kJ/mol and -49.764 +/- 1.298 kJ/mol,
respectively, with van der Waals interactions playing a major role in the
spontaneous binding. There was an 8-fold increase in the solubility of FA in a
nanosuspension compared to the bare drug. The MTT assays showed a cell viability
of 75-100% confirming the nontoxic nature of FA-NS. In vitro antibacterial
activity revealed a 16- and 18-fold enhanced activity against Staphylococcus
aureus (SA) and methicillin-resistant SA (MRSA), respectively, when compared to
bare FA. Flowcytometry showed that MRSA cells treated with FA-NS had almost twice
the percentage of dead bacteria in the population, despite having an 8-fold lower
MIC in comparison to the bare drug. The in vivo skin-infected mice showed a 76
fold reduction in the MRSA load for the FA-NS treated group compared to that of
the bare FA. These results show that the nanosuspension of antibiotics can
enhance their solubility and antibacterial activity simultaneously.
PMID- 29953818
TI - Strong Effect of Organic Ligands on the Electronic Structure of Metal
Chalcogenide Clusters.
AB - It is shown that multiple ionization energies of metal-chalcogenide clusters can
be substantially reduced by adding ligands that form charge transfer complexes.
We demonstrate this intriguing phenomenon by considering metal-chalcogenide
clusters including cases where a cluster has a filled electronic shell with a
large gap between the occupied and unoccupied states reminiscent of stable
species. The studies include a Co6Se8 core ligated with tri-ethylphosphine (PEt3)
ligands forming a stable Co6Se8(PEt3)6 species. All of the ligated clusters have
a first ionization energy in the range for alkali atoms and multiple ionization
energies that are considerably lower than those for the non-ligated clusters. The
change in electronic behavior upon ligation can be associated with a shift in the
electronic spectrum via a crystal field like effect due to attaching ligands that
form charge transfer complexes. We also show that metal-chalcogenide species can
be programmed by proper ligand replacement to promote dimerization by first
forming the Co6Se8(PEt3) n(CO)6- n ( n = 0-6) clusters where the CO ligands could
be replaced by diisocyanide (CNC6H4NC) ligands. The diisocyanide ligand acts as a
rigid linker between the metallic cores, enabling the formation of a
Co6Se8(PEt3)5(CNC6H4NC)Co6Se8(PEt3)5 superatomic molecule (SM), and we examine
the electronic and magnetic properties of the recently synthesized SM via studies
on an analogous SM with smaller ligands.
PMID- 29953817
TI - Dedoping of Lead Halide Perovskites Incorporating Monovalent Cations.
AB - We report significant improvements in the optoelectronic properties of lead
halide perovskites with the addition of monovalent ions with ionic radii close to
Pb2+. We investigate the chemical distribution and electronic structure of
solution processed CH3NH3PbI3 perovskite structures containing Na+, Cu+, and Ag+,
which are lower valence metal ions than Pb2+ but have similar ionic radii.
Synchrotron X-ray diffraction reveals a pronounced shift in the main perovskite
peaks for the monovalent cation-based films, suggesting incorporation of these
cations into the perovskite lattice as well as a preferential crystal growth in
Ag+ containing perovskite structures. Furthermore, the synchrotron X-ray
photoelectron measurements show a significant change in the valence band position
for Cu- and Ag-doped films, although the perovskite bandgap remains the same,
indicating a shift in the Fermi level position toward the middle of the bandgap.
Such a shift infers that incorporation of these monovalent cations dedope the n
type perovskite films when formed without added cations. This dedoping effect
leads to cleaner bandgaps as reflected by the lower energetic disorder in the
monovalent cation-doped perovskite thin films as compared to pristine films. We
also find that in contrast to Ag+ and Cu+, Na+ locates mainly at the grain
boundaries and surfaces. Our theoretical calculations confirm the observed shifts
in X-ray diffraction peaks and Fermi level as well as absence of intrabandgap
states upon energetically favorable doping of perovskite lattice by the
monovalent cations. We also model a significant change in the local structure,
chemical bonding of metal-halide, and the electronic structure in the doped
perovskites. In summary, our work highlights the local chemistry and influence of
monovalent cation dopants on crystallization and the electronic structure in the
doped perovskite thin films.
PMID- 29953819
TI - A Machine Learning Approach for Predicting HIV Reverse Transcriptase Mutation
Susceptibility of Biologically Active Compounds.
AB - HIV resistance emerging against antiretroviral drugs represents a great threat to
the continued prolongation of the lifespans of HIV-infected patients. Therefore,
methods capable of predicting resistance susceptibility in the development of
compounds are in great need. By targeting the major reverse transcription
residues Y181, K103, and L100, we used the biological activities of compounds
against these enzymes and the wild-type reverse transcriptase to create Naive
Bayes Networks. Through this machine learning approach, we could predict, with
high accuracy, whether a compound would be susceptible to a loss of potency due
to resistance. Also, we could perfectly predict retrospectively whether compounds
would be susceptible to both a K103 mutant RT and a Y181 mutant RT. In the study
presented here, our method outperformed a traditional molecular mechanics
approach. This method should be of broad interest beyond drug discovery efforts,
and serves to expand the utility of machine learning for the prediction of
physical, chemical, or biological properties using the vast information available
in the literature.
PMID- 29953820
TI - Fluid, Energy and Nutrient Recovery via Ad Libitum Intake of Different Commercial
Beverages and Food in Female Athletes.
AB - PURPOSE: This study investigated the effect of consuming different commercial
beverages with food ad libitum post-exercise on fluid, energy and nutrient
recovery in trained females. METHODS: On 4 separate occasions, 8 females (body
mass [BM]: 61.8+/-10.7 kg; VO2max: 46.3+/-7.5 mL.kg-1.min-1) lost 2.0+/-0.3% BM
cycling at ~75%VO2max before completing a 4 h recovery period with ad libitum
access to one of 4 beverages: Water, Powerade(r) (Sports Drink), Up & Go Reduced
SugarTM (Lower Sugar [LS]-MILK) or Up & Go EnergizeTM (Higher Protein [HP]-MILK).
Participants also had 2*15 min opportunities to access food within the first 2 h
of the recovery period. Beverage intake; total water/nutrient intake; and
indicators of fluid recovery (BM, urine output, plasma osmolality [POSM]),
gastrointestinal (GI) tolerance and palatability were assessed periodically.
RESULTS: While total water intake (from food and beverage) (Water: 1918+/-580g;
Sports Drink: 1809+/-338g; LS-MILK: 1458+/-431g; HP-MILK: 1523+/-472g; p=0.010)
and total urine output (Water: 566+/-314g; Sports Drink: 459+/-290g; LS-MILK:
220+/-53g; HP-MILK: 230+/-117g; p=0.009) differed significantly by beverage, the
quantity of ingested water retained was similar across treatments (Water: 1352+/
462g; Sports Drink: 1349+/-407g; LS-MILK: 1238+/-400g; HP-MILK: 1293+/-453g;
p=0.691). Total energy intake (from food and beverage) increased in proportion to
the energy density of the beverage (Water: 4129+/-1080kJ; Sports Drink: 5167+/
643kJ; LS-MILK: 6019+/-1925kJ; HP-MILK: 7096+/-2058kJ; p=0.014). CONCLUSION: When
consumed voluntarily and with food, different beverages promote similar levels of
fluid recovery, but alter energy/nutrient intakes. Providing access to food and
understanding the longer-term dietary goals of female athletes are important
considerations when recommending a recovery beverage.
PMID- 29953821
TI - Effects of a single bout of high-intensity interval exercise on C1q/TNF-related
proteins.
AB - High intensity interval training (HIIT) is known to be an effective exercise
training regimen to improve energy substrate metabolism and insulin sensitivity.
However, the underlying mechanisms of improvement in insulin sensitivity due to
HIIT have not yet been fully clarified. C1q/TNF-related protein (CTRP) 1 and
CTRP9, which are adiponectin paralogs and novel adipokines, have favorable
effects on energy substrate metabolism and insulin sensitivity. The purpose of
this study was to investigate the effects of a single bout of HIIT on CTRP1 and
CTRP9 secretions in healthy men. Eight healthy male subjects (mean +/- standard
error: age, 23.4 +/- 1.1 years; height, 172.1 +/- 1.7 cm; body mass, 68.0 +/- 2.0
kg; BMI, 22.9 +/- 0.5 kg/m2) participated in this study. They performed a single
bout of HIIT consisted of four 30-s maximal cycling bouts with 4-min rest between
bouts using a cycle ergometer. Blood samples were collected before the exercise,
at 0 (immediately after the exercise), 15, 30, and 120 min after the single bout
of HIIT. Serum CTRP1, CTRP9, and high-molecular-weight (HMW) adiponectin
concentrations were measured using enzyme-linked immunosolvent assay kits. CTRP1
concentration significantly increased at 120 min after the HIIT. CTRP9
concentration also significantly increased immediately after the single bout of
HIIT. In contrast, there were no significant differences in HMW adiponectin
concentration before and after the acute HIIT. These findings suggest that a
single bout of HIIT may stimulate CTRP1 and CTRP9 secretions in healthy men.
PMID- 29953822
TI - Erratum.
AB - [This corrects the article DOI: 10.5014/ajot.2018.029413.].
PMID- 29953823
TI - Opportunities for Occupational Therapy to Serve as a Catalyst for Culture Change
in Nursing Facilities.
AB - Ensuring that older adults are receiving quality and effective rehabilitation and
skilled nursing services must be a priority to society and to the health care
system, but health care policies and systems driving reimbursement continue to
challenge the delivery of services. A review of the literature indicates
significant problems among residents of skilled nursing facilities (SNFs) that
could be alleviated by meaningful occupational therapy. Research and practice in
the occupational therapy community should focus on this large area of practice.
Advocacy by individual practitioners-challenging themselves and others to provide
more patient-centered care-can lead to changes that benefit clients, facilities,
and payment systems as well as contribute to career satisfaction of occupational
therapy practitioners. Occupational therapy can and should serve as catalyst for
culture change in SNFs by providing meaningful interventions and opportunities
that support engagement and health.
PMID- 29953824
TI - Functional Ability in the Changing Demographic Landscape: Evidence and
Opportunities for Occupational Therapy.
AB - The growing number of older adults is changing the demographic landscape.
Occupational therapy can better serve the older adult population by helping them
maintain their functional ability, which is the ability to engage in occupations.
This special issue includes both studies of interventions to evaluate and support
functional ability in community-dwelling older adults and systematic reviews of
such studies. This editorial highlights the six systematic reviews, which were
completed in collaboration with the American Occupational Therapy Association's
Evidence-Based Practice Project. These reviews compile evidence for the
effectiveness of interventions within the scope of occupational therapy practice
to promote occupational performance in community-dwelling older adults. The
distinct value of occupational therapy in supporting the functional ability of
community-dwelling older adults with stable or declining health is discussed
using the World Health Organization's framework for healthy aging.
PMID- 29953825
TI - Effectiveness of Health Promotion, Management, and Maintenance Interventions
Within the Scope of Occupational Therapy for Community-Dwelling Older Adults: A
Systematic Review.
AB - OBJECTIVE: This systematic review examined the effectiveness of health promotion,
management, and maintenance interventions within the scope of occupational
therapy to improve occupational performance and quality of life (QOL) and
decrease health care utilization for community-dwelling older adults. METHOD:
Thirty-eight articles representing 36 studies were included in the review.
Articles were published 2008-2015 and described studies of participants with a
mean age of 65 or older who were living in the community. RESULTS: Strong
evidence supports the use of group, individual, or a combination of group and
individual interventions to improve occupational performance. Group interventions
were also effective at improving QOL. The evidence was insufficient that any of
these interventions decreased health care utilization. CONCLUSION: Addressing
health promotion, management, and maintenance is within the scope of occupational
therapy practice and has been shown to improve occupational performance and QOL
for older adults. Implications for practice and future research are discussed.
PMID- 29953826
TI - Occupational Therapy Interventions Supporting Social Participation and Leisure
Engagement for Community-Dwelling Older Adults: A Systematic Review.
AB - This systematic review examines the evidence for the effectiveness of
interventions within the scope of occupational therapy that address leisure
engagement and social participation among community-dwelling older adults. Eleven
Level I, 1 Level II, 1 Level III, and 1 Level IV studies met inclusion criteria.
Included articles addressed two themes: interventions supporting social
participation and interventions supporting leisure engagement. Strong evidence
supports leisure education interventions to enhance leisure engagement, and
moderate evidence supports chronic disease self-management programs to support
leisure engagement. Mixed evidence exists for community-based group interventions
and electronic gaming to support social participation. Routine use of leisure
education and chronic disease self-management programs to enhance leisure
engagement and selective use of community-based groups and electronic gaming to
support social participation are recommended.
PMID- 29953827
TI - Occupational Therapy Interventions Addressing Sleep for Community-Dwelling Older
Adults: A Systematic Review.
AB - Because of age-related changes in sleep patterns, older adults may get less sleep
than the recommended amount and experience decreased performance in daytime
activities as a result. This article examines the evidence for the effectiveness
of interventions within the scope of occupational therapy addressing sleep.
Thirteen Level I studies met inclusion criteria and were categorized into three
themes: (1) one-to-one single-component interventions, (2) one-to-one
multicomponent interventions, and (3) group multicomponent interventions. Strong
evidence supports cognitive-behavioral intervention strategies for older adults
that include relaxation, sleep hygiene education, problem solving, and physical
exercise, among others, delivered one to one or in a group. Routine use of these
interventions is recommended.
PMID- 29953829
TI - Occupational Therapy Interventions to Improve Performance of Instrumental
Activities of Daily Living for Community-Dwelling Older Adults: A Systematic
Review.
AB - OBJECTIVE: We examined the effectiveness of interventions within the scope of
occupational therapy to improve the performance of instrumental activities of
daily living (IADLs) for community-dwelling older adults. METHOD: We searched and
examined the literature (2008 through 2016) using four electronic databases.
Fourteen studies met the inclusion criteria and were critically appraised and
synthesized. RESULTS: Analysis revealed four thematic areas: cognitive, self
management, prevention, and home-based multidisciplinary rehabilitation
interventions. Strong evidence supports the use of tailored, multidisciplinary,
home-based care programs to support older adults to maintain IADL improvements
over time and the use of cognitive interventions to improve memory, executive
function, functional status, and everyday problem solving. In addition, strong
evidence indicates that tailored home-based preventive sessions were beneficial
to mediate functional disability and satisfaction with performance. CONCLUSION:
Evidence supports tailored interventions designed to enhance IADL performance.
More studies are needed that focus on IADLs specifically and that use IADLs in
their interventions.
PMID- 29953828
TI - Occupational Therapy Fall Prevention Interventions for Community-Dwelling Older
Adults: A Systematic Review.
AB - OBJECTIVE: Accidental falls among community-dwelling older adults are preventable
and increase the risk of morbidity, hospitalization, and institutionalization. We
updated and broadened a 2008 systematic review examining the evidence for the
effectiveness of fall prevention interventions in improving fall-related
outcomes, occupational performance, quality of life, and health care facility
readmissions for community-dwelling older adults. METHOD: We searched and
analyzed literature published from 2008 to 2015 from five electronic databases.
RESULTS: Fifty articles met the inclusion criteria and were critically appraised
and synthesized-37 provided Level I; 5, Level II; and 8, Level III evidence.
Analysis was organized into four intervention themes: single component,
multicomponent, multifactorial, and population based. Mixed evidence was found
for single-component and multifactorial interventions, strong evidence was found
for multicomponent interventions, and moderate evidence was found for population
based interventions. CONCLUSION: These findings can inform the delivery and
integration of fall prevention interventions from acute care to community
discharge.
PMID- 29953830
TI - Occupational Therapy Interventions to Improve Activities of Daily Living for
Community-Dwelling Older Adults: A Systematic Review.
AB - OBJECTIVE: This systematic review aimed to synthesize the effects of
interventions within the scope of occupational therapy to improve performance of
activities of daily living (ADLs) in community-dwelling older adults. METHOD:
Searches were conducted in CINAHL, the Cochrane Database of Systematic Reviews,
MEDLINE, PsycINFO, and OTseeker. Empirical studies published between 1995 and
2015 were individually screened and appraised by two reviewers. RESULTS: Forty
three studies met the review inclusion and exclusion criteria. Physical exercise
was the most common intervention approach. Physical exercise interventions for
frail older adults showed a moderate benefit, but no benefits were found for
older adults without noticeable difficulty in ADLs. For older adults with
difficulty in ADLs, there was a high benefit of using home-based intervention.
CONCLUSION: The findings of this systematic review highlight the importance of
addressing older adults' living environment in intervention to promote
independence in ADLs.
PMID- 29953831
TI - Implementing Evidence-Based Interventions With Community-Dwelling Older Adults: A
Scoping Review.
AB - OBJECTIVE: With the rapid growth of the community-dwelling older adult
population, evidence-based occupational therapy interventions targeting older
clients need to be effectively implemented. However, little is understood about
the factors influencing effective intervention implementation into practice.
METHOD: We performed a scoping review to explore what strategies and factors
relate to the uptake of older adult interventions into practice. Concepts from
implementation science literature guided our review. RESULTS: Our review yielded
13 articles that met our search criteria. Study designs examined barriers,
facilitators, and strategies related to the implementation of evidence-based
older adult interventions into practice. Effective implementation strategies
included training sessions, workshops, consultations, and outreach meetings.
CONCLUSION: Our findings suggest that practitioners, administrators, and
researchers should adopt strategies such as workshops, consultations, fidelity
vignettes, peer mentoring, and standardized training to effectively implement
research into practice with older adults.
PMID- 29953832
TI - Feasibility of Integrating Occupational Therapy Into a Care Coordination Program
for Aging in Place.
AB - OBJECTIVE: We examined the feasibility and benefit of integrating occupational
therapy into a long-term services and supports (LTSS) care coordination program
for aging in place. METHOD: Clients referred to occupational therapy during a 16
wk trial were evaluated with the In-Home Occupational Performance Evaluation and
received education on strategies for aging in place. Clients who indicated
readiness for change were assisted in setting personalized goals with goal
attainment scaling and received four additional occupational therapy visits.
RESULTS: Of the program's feasibility benchmarks, 87% were met. Twenty-three
clients were referred, and 16 clients were evaluated; 37.5% of those evaluated
indicated readiness for change, establishing 18 goals with 100% goal attainment.
CONCLUSION: Integration of occupational therapy into an LTSS care coordination
program was feasible. Benefits of adding occupational therapy included a
performance-based evaluation that revealed personal factors as barriers to aging
in place and gave access to a client-centered service to maximize independence.
PMID- 29953833
TI - Home Safety Fall and Accident Risk Among Prematurely Aging, Formerly Homeless
Adults.
AB - OBJECTIVE: Homelessness prematurely ages people. A large subgroup of formerly
homeless adults between ages 40 and 64 yr have health conditions similar to or
worse than people categorized as elderly. Little is known about the impact of
this group's chronic health conditions on their ability to safely function in
supportive housing. METHOD: Home safety visits were carried out with 25 formerly
homeless adults, ages 40-64 yr, now residing in supportive housing. RESULTS:
Participants had physical, cognitive, and mental health problems that
significantly interfered with their ability to perform daily life skills, safely
function in an apartment, and manage chronic health conditions. Home safety
hazards included cluttered walking paths, the presence of steps, and the lack of
grab bars and nonskid flooring. CONCLUSION: The homeless population would benefit
from aging specialists, such as occupational therapists, who could help people to
maintain and function more safely in their homes. Without such services, this
population may be at risk for home safety events leading to hospitalization and
mortality.
PMID- 29953834
TI - Activity Engagement and Everyday Technology Use Among Older Adults in an Urban
Area.
AB - OBJECTIVE: We investigated associations among activity engagement (AE), number of
available and relevant everyday technologies, ability to use everyday
technologies, and cognitive status among older adults in an urban area. METHOD:
This cross-sectional study included 110 participants and used three assessments:
the Frenchay Activities Index to measure AE, the Everyday Technology Use
Questionnaire to measure the number of and ability to use available and relevant
everyday technologies, and the Montreal Cognitive Assessment to measure cognitive
status. Data analyses used a one-way analysis of variance and a multiple linear
regression model. RESULTS: The number of available and relevant everyday
technologies was significantly different (p < .001) among groups that varied in
level of AE. Ability to use everyday technologies did not significantly differ
among groups. Cognitive status did not explain level of AE when the number of
available and relevant everyday technologies was considered. CONCLUSION:
Increasing the accessibility of available and relevant everyday technologies
among older adults in an urban area may increase AE.
PMID- 29953835
TI - Characteristics Influencing Diversity of Participation of Children in Activities
Outside School.
AB - OBJECTIVE: A cross-sectional survey was conducted to determine which personal and
environmental characteristics influenced diversity of participation in activities
outside school for typically developing children and adolescents. METHOD: Four
hundred twenty-two (215 boys) typically developing Australian children (mean =
11.0 yr) completed the Children's Assessment of Participation and Enjoyment
(CAPE) and the Preferences for Activity of Children to describe their
participation on five activity types: Recreational, Active Physical, Social, Self
Improvement, and Skill-Based. Linear regression analyses were conducted. RESULTS:
Predictors of participation diversity were age and preference for Recreational
(aR2 = .44); preference for Active Physical (aR2= .19); gender, school type, and
preference for Social (aR2 = .19); preference for Skill-Based (aR2 = .25); and
gender, school style, socioeconomic score, and preference for Self-Improvement
(aR2 = .24). CONCLUSION: Preference plays a key role in determining the diversity
of participation in activities outside school.
PMID- 29953836
TI - Promoting Health Through Engagement in Occupations That Maximize Food Resources.
AB - Poverty is a complex problem in the United States with far-reaching consequences,
often leading to a lack of food or lack of access to food. Proper nutrition and
food intake are foundational to health and well-being. This participatory action
research (PAR) project explored the challenges associated with living in poverty
and managing food resources. Stakeholders engaged in a multiphase PAR process,
which resulted in the development and implementation of a 7-wk occupation-based
program. The program promotes graded learning of specific skills for managing
food resources and emphasizes empowering each participant. Preliminary results
indicate statistically significant improvements in participants' ability to make
meals with certain food items and in perceived satisfaction and performance in
self-identified activities related to food resource management. These findings
support the feasibility of the program and the need for participant-driven,
occupation-based approaches to improving food security.
PMID- 29953837
TI - Ohio Modified Arm-Motor Ability Test (OMAAT): An Optimized Measure of Upper
Extremity Functional Limitation in Hemiparetic Stroke.
AB - This secondary analysis quantified the psychometric properties of the Ohio
Modified Arm-Motor Ability Test (OMAAT) in a sample of neurologically stable
chronic stroke survivors (n = 67, 40 men; mean age 59.8 yr, standard deviation =
12.8; 42 White, 23 Black, 2 other; 92.5% right-sided lesion; 44 ischemic stroke).
Findings indicate high OMAAT internal consistency (Cronbach's alpha = .97,
ordinal alpha = .98, Gugiu's bootstrap reliability = .97), unidimensionality, and
strong positive factor loadings for all 20 OMAAT items. Convergent validity
between OMAAT and Action Research Arm Test total scores was strong (r = .90, p <
.0001). The OMAAT is the first short measure of upper extremity functional
limitation available to clinicians and researchers that includes an
administration manual and that has been examined using nonparametric
psychometrics. A detailed administration manual is provided as a supplement to
this article.
PMID- 29953838
TI - Predictive Value of the Cognitive Performance Test (CPT) for Staging Function and
Fitness to Drive in People With Neurocognitive Disorders.
AB - The Cognitive Performance Test (CPT) is a standardized occupational therapy
assessment that examines cognitive integration with functioning in an
instrumental activities of daily living context. Conventional cognitive measures
provide diagnostic utility but do not fully address the functional implications.
Ninety-one veterans diagnosed with cognitive impairment were evaluated. We
compared the predictive value of the CPT with the Large Allen Cognitive Level
Screen (LACLS), Mini-Mental State Examination (MMSE), and Montreal Cognitive
Assessment (MoCA) for the need to retire from driving versus ability to pass an
on-road exam. Measures were also analyzed by diagnostic classification. CPT
correctly classified a mild versus major neurocognitive disorder, whereas MMSE,
MoCA, and LACLS did not differentiate the groups. A CPT cutoff score of <4.7/5.6
showed 89% sensitivity for failing the road exam and 75% specificity for ability
to pass. CPT discriminated functional level in neurocognitive disorders and had
better predictive value for fitness to drive compared with conventional cognitive
measures.
PMID- 29953839
TI - Occupational Therapy Practitioners' Perspectives on Occupation-Based
Interventions for Clients With Hip Fracture.
AB - OBJECTIVE: Occupational engagement is the foundation of occupational therapy. We
identified perspectives of 18 occupational therapy practitioners on integrating
occupation-based interventions during postacute care (PAC) rehabilitation for
persons with hip fracture to identify occupational therapy's distinct
contribution. METHOD: We conducted six focus groups derived from a purposive
national sample of occupational therapy practitioners (N = 18). A secondary
analysis was conducted to analyze the transcripts for major subthemes around
occupation-based interventions. RESULTS: Three major themes arose from
practitioners' perspectives regarding the role of occupation in rehabilitation:
(1) conducting an occupational profile, (2) integrating occupation-based
intervention in the facility, and (3) identifying goals for occupational
engagement after discharge. Challenges and strategies for integrating occupation
based interventions were also identified. CONCLUSION: Identifying practitioners'
perspectives on integrating occupation into rehabilitation may inform strategies
to facilitate occupation-based interventions in PAC and define occupational
therapy's role in this setting.
PMID- 29953840
TI - Leisure as an End, Not Just a Means, in Occupational Therapy Intervention.
AB - Leisure is commonly treated as a means instead of an end goal of intervention.
This approach, influenced by history and society's past values, does not reflect
the fact that leisure is meaningful and unique to its participants and has a
significant effect on their health. On the basis of the core values of the
occupational therapy profession and its role in the health care system, in this
article we advocate that occupational therapists should expand their focus to
include leisure as a goal of intervention. Although adopting this proposed
approach may not be easy, given that it involves challenges in reimbursement for
services, potential competition with other health professions, and a twisting of
the deep-rooted existing values of occupational therapists, we believe the
proposed solutions address these concerns and shed light on how to make leisure a
valued goal of intervention.
PMID- 29953841
TI - Occupational Therapy Interventions for Adults With Musculoskeletal Conditions.
AB - Evidence Connection articles provide a clinical application of systematic reviews
developed in conjunction with the American Occupational Therapy Association's
(AOTA's) Evidence-Based Practice Project. In this Evidence Connection article, we
describe a case report of a person who underwent a total knee replacement due to
severe osteoarthritis of his left knee. The occupational therapy assessment and
intervention process both before and after surgery in the home setting is
described. Findings from the systematic review (Dorsey & Bradshaw, 2017) on this
topic were published in the January/February 2017 issue of the American Journal
of Occupational Therapy and in AOTA's Occupational Therapy Practice Guidelines
for Adults With Musculoskeletal Conditions. Each article in this series
summarizes the evidence from the published reviews on a given topic and presents
an application of the evidence to a related clinical case. Evidence Connection
articles illustrate how the research evidence from the reviews can be used to
inform and guide clinical reasoning.
PMID- 29953843
TI - Identification of JNK1 as a predicting biomarker for ABT-199 and paclitaxel
combination treatment.
AB - Targeting Bcl-2 with ABT-199 (Venetoclax) shows limited single-agent activity
against many cancers in both preclinical and clinical investigations. Combination
therapies have attracted great attention. The principal purpose of this study was
to investigate the mechanism of synergism between ABT-199 and paclitaxel.
Moreover, we analyzed the biomarker to identify tumors which are most likely to
respond to this combination. We evaluated the effect of this combination in a
panel of nine cancer cell lines including cervical cancer, lung cancer, ovarian
cancer, lymphoma, leukemia and breast cancer. Combination index (CI) assay showed
that four of nine call lines exhibited synergistic respond to ABT-199/paclitaxel
combination due to enhanced intrinsic apoptosis. However, paclitaxel-induced Bcl
2 phosphorylation impaired the synergistic effect by impeding the freeing of Bax
and Bim by ABT-199 because ABT-199 cannot hit phosphorylated Bcl-2 (pBcl-2). By
means of a correlation analysis of JNK level with CI value in combination with
overexpressing or silencing JNK protein in cancer cells, we identified basal JNK1
level as a potential biomarker for predicting the level of pBcl-2 upon paclitaxel
treatment, and thus for predicting a synergistic response. A cut-off value of
0.37 for relative JNK1 expression level was determined using receiver operating
characteristic (ROC) analysis to distinguish between synergistic and non
synergistic response cancers. A more accurate and valid cut-off value for JNK1
will be gained based on a large-scale clinical samples analysis.
PMID- 29953844
TI - Critical differences in drug metabolic properties of human hepatic cellular
models, including primary human hepatocytes, stem cell derived hepatocytes, and
hepatoma cell lines.
AB - Primary human hepatocytes (PHH), HepaRGTM, HepG2, and two sources of induced
pluripotent stem cell (iPSC) derived hepatocytes were characterized regarding
gene expression and function of key hepatic proteins, important for the metabolic
fate of drugs. The gene expression PCA analysis showed a distance between the two
iPSC derived hepatocytes as well as the HepG2 and HepaRGTM cells to the three PHH
donors and PHH pool, which were clustered more closely together. Correlation
based hierarchical analysis clustered HepG2 close to the stem cell derived
hepatocytes both when the expression of 91 genes related to liver function or
only cytochrome P450 (P450) genes were analyzed indicating the non-liver feature
and a similar low P450 profile in these cell models. The specific P450 activities
and the metabolic pattern of well-characterized drug substances in the cell
models demonstrated that iPSC derived hepatocytes had modest levels of CYP3A and
CYP2C9, while CYP1A2, 2B6, 2C8, 2C9, 2C19, and 2D6 were barely detectable. High
expression of several extrahepatic P450s such as CYP1A1 and 1B1 detected in the
stem cell derived hepatocytes may have significant effects on metabolite
profiles. However, one of the iPSC derived hepatocytes demonstrated significant
combined P450 and conjugating enzyme activity of certain drugs. HepaRGTM cells
showed many metabolic properties similar to PHHs and will in many respects be a
good model in studies of metabolic pathways and induction of drug metabolism
whereas there is still ground to cover before iPSC derived hepatocytes will be
seen as a substitute to PHH in drug metabolism studies.
PMID- 29953845
TI - A safety comparative study between freezing nitrogen ethanol composite and liquid
nitrogen for cryotherapy of musculoskeletal tumors.
AB - Freezing nitrogen ethanol composite (FNEC) showed effective cryoablative ability
for bone tumor ex vivo and in vivo comparable to liquid nitrogen (LN). We
therefore wished to compare the radiant cooling damage of the surrounding tissue
between FNEC and LN. The evaluation of the radiant cooling damage was
demonstrated human bone xenograft transplantation (HXT) in a mouse model.
Characterizations and quantifications of the damaging effects on morphologic
features and apoptosis of the cryoablative surrounding bone tissue, muscle and
epidermal layer of skin were compared. The radiant cooled damaging effects
including epidermal rupture, hair follicle atrophy, dermis and subcutaneous
crystal vacuolation of skin were significantly greater in LN than FNEC. Muscular
apoptosis, structural shrinkage and bone cellular apoptosis were supposedly 15%
33% destroying degrees of LN more than FNEC. We concluded that FNEC is an
innovative cryogenic material, and it could cause less cryoablative damage to
surrounding normal tissue than LN. The findings might support the safety of FNEC
being applied in clinical cryoablation therapy.
PMID- 29953846
TI - The Big Health Data-Intelligent Machine Paradox.
PMID- 29953847
TI - Impact of intrauterine exposure to betamethasone on the testes and epididymides
of prepubertal rats.
AB - Therapy with betamethasone, a synthetic glucocorticoid, is used in cases of
preterm birth risk, in order to promote fetal lung maturation, and decrease
neonatal mortality and morbidity. However, late reproductive disorders related to
the prenatal exposure to this compound have been reported by our Laboratory, in
both male and female rats. Thus, the present study aimed to evaluate the impact
of betamethasone on postnatal reproductive development, during pre-puberty, of
male offspring exposed in utero to this synthetic glucocorticoid. For this
purpose, pregnant Wistar rats were allocated into two groups: Control, treated
with saline, and the group treated with betamethasone at 0.1 mg/kg/day. Control
and betamethasone groups were treated with intramuscular injection on gestational
days 12, 13, 18 and 19, critical days of prenatal reproductive development. The
treatment is associated with reduced body and organ weights, disorders in initial
reproductive parameters of pre-pubertal male offspring exposed in utero to
betamethasone, such as reduction of anogenital distance, alterations in
histomorphometric parameters and immunostaining pattern of androgen and estrogen
receptors on testicles and epididymides. Our results suggest that prenatal
exposure to betamethasone potentially causes reproductive reprogramming and
impairs male postnatal reproductive development. This data raise concerns about
the use of betamethasone for human antenatal therapy.
PMID- 29953848
TI - Mechanistic-based non-animal assessment of eye toxicity: Inflammatory profile of
human keratinocytes cells after exposure to eye damage/irritant agents.
AB - Eye toxicity is a mandatory parameter in human risk and safety evaluation for
products including chemicals, pesticides, medicines and cosmetics. Historically,
this endpoint has been evaluated using the Draize rabbit eye test, an in vivo
model that was never formally validated. Due to advances in scientific knowledge,
economic and ethical issues, non-animal methods based on mechanisms of toxicity
are being developed and validated for increasing the capability of these models
to predict eye toxicity. In this study, the Cytometric Bead Array (CBA) and ELISA
assays were used to evaluate the inflammatory cytokine profile produced by HaCaT
human keratinocytes after exposure to chemicals with different UN GHS eye
toxicity classifications, aiming to stablish a correlation between inflammatory
endpoints and eye toxicity (damage/irritation) potential. As a first step,
cytotoxic profile of the chemicals, including 3 non-irritants and 10 eye
toxicants (GHS Category 1, 2A and 2B), was evaluated after 24 h exposure using
MTT assay and Inhibitory Concentration of 20% of cell viability (IC20) was
calculated for each chemical. Then, the cells were exposed to these chemicals at
IC20 for 24 h and supernatants and cell lysates were analyzed by CBA assay for
quantification of the following cytokines: IL-6, IL-8, IL-10, IL-1beta, TNF and
IL-12p70. Regarding cytotoxicity evaluation, chemicals showed different
cytotoxicity profiles and data demonstrated no correlation with their UN GHS
classification. Among the cytokines evaluated, IL-1beta production has changed
after exposure and such alterations were confirmed by quantification employing
ELISA method. The higher intracellular levels of IL-1beta were found in GHS
Category 1 chemicals, followed by Category 2A and 2B, while non irritants did not
induce such increase. Thus, these findings show that IL-1beta measurement, using
HaCaT model, can be a considerable biomarker to identify chemicals according to
their potential in promote eye toxicity, differentiating damage from irritation
potential.
PMID- 29953849
TI - Efficacy Outcome Measures for Clinical Trials of USH2A Caused by the Common
c.2299delG Mutation.
AB - PURPOSE: To determine the change in vision and retinal structure in patients with
the common c.2299delG mutation in the USH2A gene in anticipation of clinical
trials of therapy. DESIGN: Retrospective observational case series. METHODS:
Eighteen patients, homozygotes or compound heterozygotes with the c.2299delG
mutation in USH2A, were studied with regard to visual acuity, kinetic perimetry,
dark- and light-adapted static perimetry, optical coherence tomography (OCT), and
autofluorescence (AF) imaging. Serial data were available for at least half of
the patients, depending on the parameter analyzed. RESULTS: The kinetics of
disease progression in this specific molecular form of USH2A differed between the
measured parameters. Visual acuity could remain normal for decades. Kinetic and
light-adapted static perimetry across the entire visual field had similar rates
of decline that were slower than those of rod-based perimetry. Horizontal OCT
scans through the macula showed that inner segment/outer segment line width had a
similar rate of constriction as co-localized AF imaging and cone-based light
adapted sensitivity extent. The rate of constriction of rod-based sensitivity
extent across this same region was twice as rapid as that of cones. CONCLUSIONS:
In patients with the c.2299delG mutation in USH2A, rod photoreceptors are the
cells that express disease early and more aggressively than cones. Rod-based
vision measurements in central or extracentral-peripheral retinal regions warrant
monitoring in order to complete a clinical trial in a timely manner.
PMID- 29953851
TI - TAZQ233del Hijacks Hippo pathway to promote mesenchymal-epithelial transition in
pancreatic adenocarcinoma cells.
AB - The Hippo pathway is crucial in organ size control, and its dysregulation
contributes to tumorigenesis. TAZ is an essential molecule containing a WW domain
in Hippo pathway and serves as transcription co-activator to modulate cell
proliferation and induce epithelial-mesenchymal transition in different human
cancers, including pancreatic adenocarcinoma. In this study, we found that
TAZQ233del, a deletion occurred at its transactivation domain, increases
phosphorylation at TAZ Ser89, resulting in sequestration of TAZ in cytoplasm and
inhibiting its transcriptional activity. Furthermore, ectopic expression of
TAZQ233del promotes mesenchymal-epithelial transition (MET), demonstrating that
Q233 is an essential site to control TAZ function. Our results disclose that
TAZQ233del plays a major role in regulating malignancy of cancer cells by
hijacking Hippo pathway.
PMID- 29953852
TI - Induction of the mitochondrial NDUFA4L2 protein by HIF-1a regulates heart
regeneration by promoting the survival of cardiac stem cell.
AB - The adult mammalian heart doesn't regenerate after cardiomyocyte injury, which
was mainly caused by the severe and persistent effects of cardiomyopathy.
Recently, some studies reported that the mammalian heart can regenerate under low
oxygen environment. However, the mechanism that the mammalian heart can
regenerate remains unknown. Here, we used cardiac stem cells (CSCs) to be planted
in serum-free medium under hypoxia environment to understand the mechanism of
HIF1alpha/NDUFA4L2 in the regulation of hypoxia-alleviated apoptosis. Our results
revealed that hypoxia can alleviated CSCs apoptosis. Hypoxia inhibited the level
of cleaved-caspase3 and stimulated the expression of stabilized HIF-1alpha. DMOG
promotes the survival of CSCs and the protein expression of NDUFA4L2. 2-ME
repressed the survival of CSCs and the protein expression of NDUFA4L2. CHIP assay
showed that HIF-1alpha regulated the survival of CSCs by augmenting the
combination of HIF-1alpha and NDUFA4L2's HRE. Knockdown of NDUFA4L2 reversed the
role of hypoxia in the survival of CSCs. Taken together, hypoxia promotes the
viability of CSCs in serum-free medium by HIF-1alpha/NDUFA4L2 signaling pathway.
PMID- 29953850
TI - Clinical value of anti-domain I-beta2Glycoprotein 1 antibodies in
antiphospholipid antibody carriers. A single centre, prospective observational
follow-up study.
AB - BACKGROUND: There seems to be a clear correlation between antibodies against
domain I (anti-DI) of beta2Glycoprotein I and severe clinical profiles in
antiphospholipid syndrome (APS) patients. We investigated the clinical
significance of anti-DI antibodies in a cohort of aPL carriers. METHODS: One
hundred and five carriers persistently positive for IgG anti-beta2Glycoprotein 1
antibodies (a-beta2GPI) and/or IgG anticardiolipin (aCL) and/or lupus
anticoagulants (LAC) were tested for the presence of anti-DI antibodies using the
QUANTA Flash(r) Beta2GPI-Domain I chemiluminescence immunoassay. RESULTS: Anti-DI
antibodies were detected in 44 aPL carriers (41.9%) and they were significantly
associated to triple aPL positivity (LAC plus IgG a-beta2GPI plus IgG aCL
antibodies). Isolated LAC and a-beta2GPI antibodies were significantly associated
to anti-DI negative aPL carriers. During a 82.2 month mean follow-up, ten aPL
carriers (9.5%) developed a first thrombotic event so becoming APS patients. Anti
DI antibodies, triple aPL positivity, thromboembolic risk factors and autoimmune
disorders significantly prevailed in carriers becoming APS. Logistic regression
analysis showed that anti-DI positivity was an independent risk factor for
thrombosis. CONCLUSIONS: Anti-DI antibody positivity can be considered a new risk
factor predictive of the first thrombotic event in aPL carriers, instead,
negative anti-DI may be useful to identify low-risk aPL carriers.
PMID- 29953853
TI - Tankyrase regulates apoptosis by activating JNK signaling in Drosophila.
AB - Programmed cell death (PCD), or apoptosis, plays essential roles in various
cellular and developmental processes, and dysregulation of apoptosis causes many
diseases. Thus, regulation of apoptotic process is very important. Drosophila
tankyrase (DTNKS) is an evolutionarily conserved protein with poly(ADP-ribose)
polymerase activity. In mammalian cells, tankyrases (TNKSs) have been reported to
regulate cell death. To determine whether DTNKS plays function in inducing
apoptosis in in vivo development, we used Drosophila as a model system and
generated transgenic flies expressing DTNKS. We show that ectopic expression of
DTNKS promotes caspase-dependent apoptosis and knockdown of DTNKS by RNAi
dramatically alleviates apoptotic defect caused by ectopic expression of pro
apoptotic protein hid or rpr in the adult eye. Moreover, our result shows that
ectopic expression of DTNKS triggers the activation of c-Jun N-terminal kinase
(JNK) signaling, which is required for DTNKS-mediated apoptosis. Taken together,
our finding identifies the role of DTNKS in regulating apoptosis by activating
JNK signaling in Drosophila.
PMID- 29953854
TI - Morphogenesis of aligned collagen fibers in the annulus fibrosus: Mammals versus
avians.
AB - The mammalian intervertebral disc (IVD) consists of a gel-like, disordered
nucleus pulposus (NP) surrounded by a highly ordered collagen structure, the
annulus fibrosus (AF). While this concentric array of lamellae has been amply
studied, its physical origin is poorly understood. The notochord is a rod-like
organ located in the mid-line of the growing embryo and plays an essential role
in IVD development. The aim of this study was to elucidate the effect of
notochord development on the collagen fiber arrangement evolution in the AF. To
that end, we studied IVD development in mouse embryos and compared these
observations to those from chicken embryos, which do not form the typical laminar
structure around the NP. In mouse, cross-aligned collagen arrangement of the AF
forms from the sclerotome upon bulging of the notochord to become NP. By
contrast, the notochord in the chicken embryo swells substantially without the
physical restrictions of the future vertebrae and thus do not bulge. From these
observations, we conclude that physical and geometrical constrictions are
essential for the formation of the highly structured AF.
PMID- 29953855
TI - Mutant cytoskeletal and ECM peptides sensitive to the ST14 protease are
associated with a worse outcome for glioblastoma multiforme.
AB - We previously identified a set of the most frequently mutated cytoskeleton- and
extracellular matrix-related proteins (CECMPs) in numerous cancer datasets. In
this report, we used a bioinformatics approach to assess the impact of amino acid
(AA) substitutions on the sensitivity of CECMPs to the ST14 protease (matriptase
I), a transmembrane serine protease previously implicated in cancer development.
Results indicated that AA substitutions in glioblastoma multiforme (GBM) CECMPs
are skewed toward increased resistance to the ST14 protease, in comparison to the
wild-type peptide sequence. Furthermore, the protease resistant AA substitutions
represent relatively high binding affinities to HLA class I proteins, when
assessing the binding specificities using HLA class I alleles matched to the
source of the mutant AA. Moreover, samples representing AA substitutions that
increased protease sensitivity also represented reduced overall and disease-free
survival periods for patients with glioblastoma. To assess tumor specimen
immunogenicity, we identified T-cell receptor (TCR) V(D)J recombinations in GBM
exome files. The overlap between ST14 protease sensitive mutant barcodes and the
TCR V(D)J recombination read positive barcodes represented significantly reduced
survival.
PMID- 29953856
TI - Benefits of long-term pilocarpine due to increased muscarinic acetylcholine
receptor 3 in salivary glands.
AB - Hypofunction of the salivary gland causes several life-disrupting side effects
such as dental caries, oral candidiasis, loss of taste, and swallowing disorders.
No satisfactory therapy has been established to treat salivary hypofunction.
Pilocarpine represents a potential treatment for dry mouth due to Sjogren's
syndrome (SS). Although subjective improvement was consistently observed with
pilocarpine therapy, the mechanism was unclear. In this study, we investigated
the mechanism of recovery in salivation following treatment with pilocarpine. We
first examined the effectiveness of pilocarpine in SS patients as quantified by
the Saxon test and the visual analogue scale average. We found that salivation
ability and subjective symptoms improved by continuous administration of
pilocarpine. These results demonstrated that long-term medication for dry mouth
patients was more effective. However, as the mechanism remained unclear,
molecular biological mechanisms were analyzed based on the effects of continuous
administration of pilocarpine using model mice. In the molecular biological
analysis, continuous administration of pilocarpine was effective in both ICR and
SS model mice. Gene and protein expression of muscarinic acetylcholine receptor 3
(M3R) increased in salivary glands following continuous administration of
pilocarpine compared with single administration. Therefore, continuous
administration of pilocarpine effectively induced M3R expression, thereby
activating salivation.
PMID- 29953857
TI - The peptide mimicking small extracellular loop domain of CD82 inhibits tumor cell
migration, adhesion and induces apoptosis by inhibiting integrin mediated
signaling.
AB - Within the extracellular domains of metastasis suppressor CD82, the large
extracellular loop (EC2) has received much of the attention and its structure and
function have been studied in detail. However, little attention has been given to
the small extracellular loop (EC1 domain). To investigate the function role of
EC1 in metastasis suppression of CD82, the peptide mimicking EC1 amino acid
sequence (EC1-mP) was synthesized and its effect on cancer cells behavior was
examined. Here, we reported that EC1-mP strongly inhibited cancer cell migration
in vitro, attnuated the ability of cancer cells adhesion to fibronectin, and
induced the apoptosis. Furthermore, the EC1-mP was showed to supprese the
expressions of integrins alpha5 and beta1, as well as decreased the
phosphorylation of FAK and expression of ILK in SW620 cells. Taken together,
these results demonstrate that this small peptide has the functional role of CD82
intact molecule. This novel finding will improve our understanding of the
mechanism by which CD82 inhibits metastasis, and suggested that EC1 mimic peptide
may be a promising candidate for developing anti-metastasis drugs.
PMID- 29953858
TI - Ephrin-B3 binds both cell-associated and secreted proteoglycans.
AB - The ephrin family of membrane proteins binds Eph tyrosine kinase receptors. We
have previously shown that ephrin-B3 also binds to heparan sulfate proteoglycans
(HSPGs). We now show that ephrin-B3 can bind both secretory and cell associated
PGs, such as agrin, collagen XVIII, Perlecan, and CD44, and indicate that such
interaction with cell associated PGs involves a complex including 20 and 45 kDa
proteins. Ephrin-B3 binding to HEK-293T cells is blocked by a secretory variant
of CD44 (v3-v10), while over-expression of membrane associated CD44 increased
ephrin-B3 binding. In addition, ephrin-B3 precipitated CD44 expressed by the oral
squamous carcinoma cell line H376. Moreover, ephrin-B3 binding affinities to
heparin and CD44 in solution was strong. In conclusion, we have identified
secretory and cell associated PGs with high ability to bind ephrin-B3 and suggest
that ephrin-B3 can bind to a protein complex organized by a membrane associated
PG.
PMID- 29953859
TI - High expression of fibroblast growth factor-21 in liposarcoma patients indicated
better prognosis and less recurrence.
AB - Liposarcoma is the most common soft tissue malignancy. We investigated the
relationship between the expression of fibroblast growth factor -21 protein and
recurrence in the liposarcoma tissues from 40 patients. The patients were divided
into two groups (low/no- and high-expressing) for further survival analysis
according to fibroblast growth factor -21 expression in their tumor tissue.
Immunohistochemical staining showed that fibroblast growth factor -21 protein was
located in the cytoplasm. The fibroblast growth factor -21 protein was
significantly less expressed in liposarcoma than in normal tissue (p < 0.05).
Fibroblast growth factor -21 protein expression was related to gender, but not
age, cell differentiation or tumor size. The patients in the low/no fibroblast
growth factor 21 expression group were more likely to relapse and die in a
shorter period of time. The patients in the high-expression group had a better
prognosis and less recurrence. fibroblast growth factor -21 has the potential to
act both as a biomarker for liposarcoma prognosis as well as a marker for the
response to therapy.
PMID- 29953860
TI - Inhibitory effect of 11-carbonyl-beta-boswellic acid on non-small cell lung
cancer H446 cells.
AB - BACKGROUND: The anti-lung tumor potential of 11-carbonyl-beta-boswellic acid was
investigated. MATERIALS & METHODS: The inhibitory effects of 11-carbonyl-beta
boswellic acid on non-small cell lung cancer (NSCLC) was assessed by
proliferation, apoptosis, cell cycle and molecular mechanisms in NSCLC H446 cells
in vitro. The results showed that the growth of H446 cells was significantly
inhibited by 11-carbonyl-beta-boswellic acid in a dose- and time-dependent
manner. Meanwhile, 11-carbonyl-beta-boswellic acid induced cell apoptosis and
cell cycle G2-M phase arrest in H446 cells. RESULTS: Mechanistically, 11-carbonyl
beta-boswellic acid could activate JNK signaling pathway, down-regulate the
expression of surviving protein, and activate the cleavage of PARP, leading to
marked inhibitory effect on H446 cells. CONCLUSIONS: These findings suggest that
11-carbonyl-beta-boswellic acid may be a potential usefulness for preventing and
treatment of NSCLC.
PMID- 29953861
TI - Inhibition of GLUTs by WZB117 mediates apoptosis in blood-stage Plasmodium
parasites by breaking redox balance.
AB - Like tumour cells, during intraerythrocytic stage, Plasmodium-infected
erythrocytes rely completely on glucose absorption from the blood circulation for
energy metabolism. Glucose is taken up by glucose transporter 1 (GLUT1) on human
red blood cells (RBCs) and glucose transporter 4 (GLUT4) on rodent RBCs. Blood
stage parasites grow rapidly; therefore, infected red blood cells (iRBCs) need
much more glucose for energy. In previous study, WZB117 (2-fluoro-6-(m
hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits GLUT1 by binding the
exofacial sugar-binding site and inhibits the insulin-sensitive GLUT4 with
greater potency than its inhibition of either GLUT1 or GLUT3. In our study,
WZB117 effectively inhibit the growth of blood-stage parasites. Mechanistically,
WZB117 inhibited the activity of GLUTs and perturbed the glycolysis. Therefore,
decreasing the glucose level increased the redox oxidative species (ROS) level
and induced oxidative stress and apoptosis. The spleen can more easily clear
apoptopic iRBCs than nonapoptotic iRBCs, effectively relieving
hepatosplenomegaly. These findings provide important insights into the crucial
role of glucose transporters (GLUTs) in Plasmodium glucose uptake during intra
erythrocytic stage, as the inhibition of GLUTs block Plasmodium infection during
the erythrocytic stage.
PMID- 29953862
TI - Practical Computational Reproducibility in the Life Sciences.
AB - Many areas of research suffer from poor reproducibility, particularly in
computationally intensive domains where results rely on a series of complex
methodological decisions that are not well captured by traditional publication
approaches. Various guidelines have emerged for achieving reproducibility, but
implementation of these practices remains difficult due to the challenge of
assembling software tools plus associated libraries, connecting tools together
into pipelines, and specifying parameters. Here, we discuss a suite of cutting
edge technologies that make computational reproducibility not just possible, but
practical in both time and effort. This suite combines three well-tested
components-a system for building highly portable packages of bioinformatics
software, containerization and virtualization technologies for isolating reusable
execution environments for these packages, and workflow systems that
automatically orchestrate the composition of these packages for entire pipelines
to achieve an unprecedented level of computational reproducibility. We also
provide a practical implementation and five recommendations to help set a typical
researcher on the path to performing data analyses reproducibly.
PMID- 29953863
TI - Phenotypic Image Analysis Software Tools for Exploring and Understanding Big
Image Data from Cell-Based Assays.
AB - Phenotypic image analysis is the task of recognizing variations in cell
properties using microscopic image data. These variations, produced through a
complex web of interactions between genes and the environment, may hold the key
to uncover important biological phenomena or to understand the response to a drug
candidate. Today, phenotypic analysis is rarely performed completely by hand. The
abundance of high-dimensional image data produced by modern high-throughput
microscopes necessitates computational solutions. Over the past decade, a number
of software tools have been developed to address this need. They use statistical
learning methods to infer relationships between a cell's phenotype and data from
the image. In this review, we examine the strengths and weaknesses of non
commercial phenotypic image analysis software, cover recent developments in the
field, identify challenges, and give a perspective on future possibilities.
PMID- 29953865
TI - A Stable Neural Code for Birdsong.
AB - Proteins, synapses, and neural connections are in constant flux, yet motor
behaviors somehow remain stable. In this issue of Neuron, Katlowitz et al. (2018)
show that temporally precise neural activity driving birdsong production is
stable for weeks.
PMID- 29953864
TI - Community-Driven Data Analysis Training for Biology.
AB - The primary problem with the explosion of biomedical datasets is not the data,
not computational resources, and not the required storage space, but the general
lack of trained and skilled researchers to manipulate and analyze these data.
Eliminating this problem requires development of comprehensive educational
resources. Here we present a community-driven framework that enables modern,
interactive teaching of data analytics in life sciences and facilitates the
development of training materials. The key feature of our system is that it is
not a static but a continuously improved collection of tutorials. By coupling
tutorials with a web-based analysis framework, biomedical researchers can learn
by performing computation themselves through a web browser without the need to
install software or search for example datasets. Our ultimate goal is to expand
the breadth of training materials to include fundamental statistical and data
science topics and to precipitate a complete re-engineering of undergraduate and
graduate curricula in life sciences. This project is accessible at
https://training.galaxyproject.org.
PMID- 29953866
TI - Parkinson's Disease: Mitochondria Parked at the ER Hit the Snooze Button.
AB - Parkinson's disease patients report sleep disturbances well ahead of motor
symptoms. In this issue of Neuron, Valadas et al. (2018) report that the disease
genes pink1 and parkin exert novel, cell-type-specific effects to modulate ER
mitochondria contacts, neuropeptidergic transmission, and sleep patterns.
PMID- 29953867
TI - Shining a Light on Olfactory Circuits.
AB - How is odor information organized in the brain? In this issue of Neuron, Jeanne
et al. (2018) pair optogenetics with electrophysiology to map functional
connections between two olfactory brain regions. They suggest that lateral horn
neurons encode "odor scenes" to represent biologically relevant odor
environments.
PMID- 29953868
TI - Acetylcholine Receptor Stimulation for Cognitive Enhancement: Better the Devil
You Know?
AB - Drug treatments to improve memory focus on enhancing acetylcholine. However,
Vijayraghavan and colleagues (2018) show that direct stimulation of the M1
muscarinic acetylcholine receptor adversely affected neuronal activity in
prefrontal cortex related to working memory for behavioral rules.
PMID- 29953869
TI - Zen and the Art of Making a Bayesian Espresso.
AB - In this issue of Neuron, Konovalov and Krajbich (2018) argue that a Bayesian
inference is employed when learning new sequences and identify distinct brain
networks that track the uncertainty of both the current state and the underlying
pattern structure.
PMID- 29953870
TI - Investigating the Neural Encoding of Emotion with Music.
AB - Does our understanding of the human brain remain incomplete without a proper
understanding of how the brain processes music? Here, the author makes a
passionate plea for the use of music in the investigation of human emotion and
its brain correlates, arguing that music can change activity in all brain
structures associated with emotions, which has important implications on how we
understand human emotions and their disorders and how we can make better use of
beneficial effects of music in therapy.
PMID- 29953871
TI - Glutamatergic Signaling in the Central Nervous System: Ionotropic and
Metabotropic Receptors in Concert.
AB - Glutamate serves as both the mammalian brain's primary excitatory
neurotransmitter and as a key neuromodulator to control synapse and circuit
function over a wide range of spatial and temporal scales. This functional
diversity is decoded by two receptor families: ionotropic glutamate receptors
(iGluRs) and metabotropic glutamate receptors (mGluRs). The challenges posed by
the complexity and physiological importance of each of these subtypes has limited
our appreciation and understanding of how these receptors work in concert. In
this review, by comparing both receptor families with a focus on their crosstalk,
we argue for a more holistic understanding of neural glutamate signaling.
PMID- 29953873
TI - APOE4 Causes Widespread Molecular and Cellular Alterations Associated with
Alzheimer's Disease Phenotypes in Human iPSC-Derived Brain Cell Types.
PMID- 29953874
TI - Practical evaluation of 11 de novo assemblers in metagenome assembly.
AB - Next Generation Sequencing (NGS) technologies are revolutionizing the field of
biology and metagenomic-based research. Since the volume of metagenomic data is
typically very large, De novo metagenomic assembly can be effectively used to
reduce the total amount of data and enhance quality of downstream analysis, such
as annotation and binning. Although, there are many freely available assemblers,
but selecting one suitable for a specific goal can be highly challenging. In this
study, the performance of 11 well-known assemblers was evaluated in the assembly
of three different metagenomes. The results obtained show that metaSPAdes is the
best assembler and Megahit is a good choice for conservative assembly strategy.
In addition, this research provides useful information regarding the pros and
cons of each assembler and the effect of read length on assembly, thereby helping
scholars to select the optimal assembler based on their objectives.
PMID- 29953872
TI - Synaptojanin and Endophilin Mediate Neck Formation during Ultrafast Endocytosis.
AB - Ultrafast endocytosis generates vesicles from the plasma membrane as quickly as
50 ms in hippocampal neurons following synaptic vesicle fusion. The molecular
mechanism underlying the rapid maturation of these endocytic pits is not known.
Here we demonstrate that synaptojanin-1, and its partner endophilin-A, function
in ultrafast endocytosis. In the absence of synaptojanin or endophilin, the
membrane is rapidly invaginated, but pits do not become constricted at the base.
The 5-phosphatase activity of synaptojanin is involved in formation of the neck,
but 4-phosphatase is not required. Nevertheless, these pits are eventually
cleaved into vesicles; within a 30-s interval, synaptic endosomes form and are
resolved by clathrin-mediated budding. Then synaptojanin and endophilin function
at a second step to aid with the removal of clathrin coats from the regenerated
vesicles. These data together suggest that synaptojanin and endophilin can
mediate membrane remodeling on a millisecond timescale during ultrafast
endocytosis.
PMID- 29953875
TI - New genotyping method for the causative agent of crayfish plague (Aphanomyces
astaci) based on whole genome data.
AB - The oomycete Aphanomyces astaci causes crayfish plague, the most important
disease of European freshwater crayfish species. Presumably introduced into
Europe 150 years ago with the import of North American crayfish, A. astaci is
highly pathogenic to European crayfish species. Five genotypes (A, B, C, D, and
E) have been defined based on random amplified polymorphic DNA analysis (RAPD
PCR) from A. astaci pure cultures. The distinction of genotypes is an essential
tool to conduct molecular epidemiological studies on crayfish plague and it has
been used to clarify and better understand the history and spread of this disease
in Europe. Whereas RAPD-PCR requires DNA from pure culture isolates, the
development of genotyping tools that can be applied to DNA extracted from
clinical samples allows a much wider application of genotyping studies, including
revisiting historic samples. In this study, we present a new approach that adds
to currently available methods for genotyping A. astaci strains directly from
clinical crayfish samples. Whole-genome sequencing of A. astaci strains
representing all currently known genotypes was employed, genomic regions unique
to the respective genotype identified, and a PCR-based genotyping assay designed,
which focuses on the presence/absence of PCR product after amplification with the
genotype-specific primers. Our diagnostic methodology was tested using DNA
extracts from pure A. astaci cultures, other Aphanomyces species and additional
oomycetes, samples from a recent Italian crayfish plague outbreak and additional
historical samples available in the Centre for Environment, Fisheries and
Aquaculture Science laboratory. The new markers were reliable for pure culture
and clinical samples from a recent outbreak and successfully discriminated
genotype A, B, D, and E. The marker for genotype C required an additional
sequencing step of the generated PCR product to confirm genotype.
PMID- 29953876
TI - The prebiotic inulin improves substrate metabolism and promotes short-chain fatty
acid production in overweight to obese men.
AB - BACKGROUND AND AIMS: Human gut microbiota play an important role in maintaining
human health. Dietary fibers, i.e. prebiotics, are fermented by human gut
microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and
butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore,
the prebiotic inulin might be an effective dietary strategy to improve human
metabolism. We aimed to investigate the acute metabolic effects of ingesting
inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs
using stable isotope tracer methodology. METHODS: In a double-blind, randomized,
placebo-controlled crossover design, 14 healthy, overweight to obese men consumed
a high-fat milkshake containing A) 24 g inulin of which 0.5 g was U-13C-inulin
(INU) or B) 24 g maltodextrin placebo (PLA), with a wash-out period of at least
five days. Fat oxidation was measured via an open-circuit ventilated hood and
blood samples were collected up to 7 h after ingestion. Plasma, breath, and fecal
samples were collected, and appetite and satiety scores were assessed. RESULTS:
Fat oxidation increased in the early postprandial phase (0-3 h), and both plasma
glucose and insulin were lower after INU ingestion compared with PLA (all P <
0.05). Plasma free fatty acids were higher in the early, and lower in the late
postprandial period after INU ingestion. Inulin was fermented into SCFAs as
indicated by higher plasma acetate concentrations after INU compared with PLA (P
< 0.05). In addition, we found continuous increases in plasma 13C-SCFA
enrichments (P < 0.05 from t = 120 onwards) and breath 13CO2 enrichments after
INU intake. There were no effects on plasma triglycerides, free glycerol, satiety
hormones GLP-1 and PYY, and appetite and satiety scores. CONCLUSIONS: Ingestion
of the prebiotic inulin improves fat oxidation and promotes SCFA production in
overweight to obese men. Overall, replacing digestible carbohydrates with the
fermentable inulin may favor human substrate metabolism. CLINICAL TRIAL REGISTRY:
The trial was registered at clinicaltrials.gov under number NCT02009670.
PMID- 29953878
TI - Metabolic and Bariatric Surgery: An Effective Treatment Option for Obesity and
Cardiovascular Disease.
AB - Obesity is a chronic and debilitating disease that has become a global epidemic.
Especially severe in the Unites States, obesity currently affects almost 40% of
the population. Obesity has a strong causal relationship with numerous serious
comorbidities that impair quality of life, shorten life expectancy, and carry a
major economic burden. Obesity has particular relevance to cardiologists because
it contributes directly to several major cardiovascular diseases and,
consequently, increases overall cardiovascular mortality. Multiple treatment
options are available, but metabolic and bariatric surgery offers the most
effective and durable treatment for obesity. Moreover, metabolic and bariatric
operations alleviate and often completely eliminate numerous comorbidities,
particularly type 2 diabetes and other cardiovascular risk factors, such as
hypertension and dyslipidemia. With their low risk of complications and
morbidity, metabolic and bariatric operations significantly improve quality of
life and overall survival, particularly reducing death due to cardiovascular
disease.
PMID- 29953877
TI - Myosin-IIA heavy chain phosphorylation on S1943 regulates tumor metastasis.
AB - Nonmuscle myosin-IIA (NMHC-IIA) heavy chain phosphorylation has gained
recognition as an important feature of myosin-II regulation. In previous work, we
showed that phosphorylation on S1943 promotes myosin-IIA filament disassembly in
vitro and enhances EGF-stimulated lamellipod extension of breast tumor cells.
However, the contribution of NMHC-IIA S1943 phosphorylation to the modulation of
invasive cellular behavior and metastasis has not been examined. Stable
expression of phosphomimetic (S1943E) or non-phosphorylatable (S1943A) NMHC-IIA
in breast cancer cells revealed that S1943 phosphorylation enhances invadopodia
function, and is critical for matrix degradation in vitro and experimental
metastasis in vivo. These studies demonstrate a novel link between NMHC-IIA S1943
phosphorylation, the regulation of extracellular matrix degradation and tumor
cell invasion and metastasis.
PMID- 29953880
TI - Diabetex: A novel approach for diabetic wound healing.
AB - INTRODUCTION AND AIM: Wound healing is an orderly complex process involving
inflammation, clotting, re-epithelialization, neovascularization and wound
closure. In diabetic patients, such process is impaired and delayed, posing
negative economic as well as social consequences. Diabetex, (patency# EP 0877617
A1) composed of L-alanine, d-ribose, nicotinic acid and calcium ascorbate, which
was initially introduced to treat cancer is thought to have anti- diabetic
effects. The present study was designed to investigate the therapeutic merit of
diabetex as well as the cellular mechanisms involved in such effects and its
safety profile compared to metformin in wounded diabetic rats. MAIN METHODS:
Sixty adult male Sprague-Dawley albino rats were randomly divided into two major
groups after induction of full thickness wound; control and treated groups. Liver
and kidney function test, as well as cytokines (VEGF, TGF-beta, PDGF and MMP2),
fasting blood sugar were measured in animal sera. Histopathological studies
including hematoxyline and eosin, Masson's trichrome stains were performed on
wounded tissue. KEY FINDINGS: Diabetex significantly improved wound healing,
collagen formation, induced re-epithelialization and neovascularization.
Moreover, cytokines involved in wound healing process were increased by the
antidiabetic medication. Noteworthy, the drug exhibited a safe profile on liver
and kidney function tests and significantly reduced fasting blood sugar.
SIGNIFICANCE: The present study offers a novel approach for treating diabetic
resistant wounds with a possible more economic, safe strategy.
PMID- 29953879
TI - The effect of P85 on neuronal proliferation and differentiation during
development of mouse cerebral cortex.
AB - Proliferation of neural stem cells and differentiation of newly generated cells
are crucial steps during the development of mammalian neocortex, which are able
to generate suitable number of neurons and glial cells to ensure normal formation
of cortex. Any disturbance in these processes leads to structural and functional
abnormalities of cerebral cortex, such as epilepsy or intellectual disability.
Numerous molecules involved in the development of disorders of the nervous system
have been discovered in the recent years. The PI3K/AKT signaling pathway has been
shown to be widely involved in the corticogenesis. Recently we could show that
overexpression of regulatory subunit P85 of PI3K disrupts neuronal migration.
However, it remains unclear whether the regulatory subunit P85 plays a role in
the proliferation of neural stem cells and differentiation of newly generated
cells during mouse brain development. Here, by using in utero electroporation and
immunohistochemistry, we show that overexpression of P85 inhibited proliferation
of neural progenitor cells and neuronal differentiation. By using 5-bromo-2
deoxyuridine (BrdU) labeling, we reveal that overexpression of P85 extended the
cell cycle duration, which may result in developmental retardation during mouse
corticogenesis.
PMID- 29953881
TI - Structural studies on inhibitory mechanisms of antibiotic, corticosteroid and
catecholamine molecules on lactoperoxidase.
AB - AIM: Lactoperoxidase (LPO) is an essential protein with broad spectrum
antimicrobial activity present in mammalian milk. It imparts immunity to infants
against wide range of pathogenic infections. Several in vitro studies have shown
inhibition of LPO activity by pharmaceutical compounds including commonly used
antibiotics such as ampicillin and gentamicin, and molecules like prednisolone,
norepinephrine, etc. Prescription of such drugs to lactating mothers might have
adverse health effects on infants. The aim of our study was the elucidation of
the structural aspects of the inhibitory mechanism of ampicillin, gentamicin,
amoxicillin, prednisolone and norepinephrine on LPO. MATERIAL AND METHODS: Three
dimensional structure of camel LPO (cLPO) was developed using homology modeling
and used for in silico experimental studies. The Schrodinger induced fit docking
along with binding affinity estimation experiments were performed. The cLPO and
Ligands were prepared using Protein Preparation Wizard and Ligprep modules
available in Schrodinger suite. For estimating Binding affinity Prime Molecular
Mechanics with Generalized Born and Surface Area (MMGB-SA) module was used. KEY
RESULTS: The five drug ligands formed three to five hydrogen bonding interactions
with cLPO. Amino acids Arg-231, Asp-232, Ser-370, Arg-371 and Glu-374 of cLPO
were crucial for these interactions. The binding affinity values for gentamicin
were highest and for norepinephrine were the lowest. SIGNIFICANCE: This study
concludes that the five drug molecules show potential ability to inhibit the LPO
activity. Further, a very high sequence similarity of cLPO with human LPO imparts
high significance to these conclusions in relation to human health especially in
new born infants.
PMID- 29953882
TI - Adipokines expression profile in liver, adipose tissue and muscle during chicken
embryo development.
AB - In broiler chickens, the intense genetic selection for rapid growth has resulted
in an increase in growth rate and fat deposition. Adipose tissue is now
recognized as an important endocrine organ that secretes a variety of factors
including adipokines. However, the expression pattern of these adipokines is
unclear in chicken embryo development. In the present study, we determined the
expression profile of three novel adipokines, NAMPT, RARRES2 and ADIPOQ, and
their cognate receptors in metabolic tissues (liver, muscles and adipose tissue)
of chicken embryo/chicks from 15 days of incubation (E15) to hatching (D0). From
E15 to hatching, embryos gradually gained weight and started to develop
subcutaneous adipose tissue at E15. We conducted western blot and RT-qPCR tests
and found that ADIPOQ expression increased over time and was positively
correlated with adipose tissue weight. In addition, NAMPT expression increased
only in muscles. By using a new homemade chicken RARRES2 specific antibody we
showed that RARRES2 protein levels increased specifically at hatching in adipose
tissue, liver and pectoralis major and this was associated with an increase in
the weight of embryo. Taken together, these results support a potential
involvement of adipokines in metabolic regulation during chicken embryo
development.
PMID- 29953883
TI - Long-term Natural History of Lower Urinary Tract Symptoms Following Radical
Retropubic Prostatectomy: A Prospective 15-Year Longitudinal Study.
AB - OBJECTIVE: To provide insights into the long-term impact of radical retro-pubic
prostatectomy (ORRP) on lower urinary tract symptoms (LUTS) which are age and
prostate dependent and adversely impact quality of life. METHODS: 1995 men
undergoing ORRP enrolled in a prospective longitudinal outcomes study. The
American Urological Association Symptom Index was self-administered before ORRP
and at predetermined time-points after surgery. A multivariate generalized linear
model was used to evaluate the association of time since ORRP with American
Urological Association symptom score (AUASS). McNemar's test and paired sample t
tests were used to assess whether the proportion of men with clinically
significant LUTS (CSLUTS) defined by an AUASS >7 or mean AUASS differed
significantly between the time-dependent assessments, respectively. RESULTS: The
15-year mean adjusted AUASS was similar to baseline (7.00 vs 6.85, P = .66).
Throughout the 15 years of follow-up, the proportion of men with CSLUTS was lower
than baseline with the exception of the 3 month and 15 year assessments. Among
men with baseline clinically insignificant LUTS (CILUTS), the mean adjusted AUASS
at 15 years was significantly greater than baseline (6.09 vs 3.19, P < .001).
Among men with baseline CSLUTS, ORRP led to a significant decrease in mean
adjusted AUASS between baseline and 15 years (13.26 vs 8.67, P < .001).
CONCLUSION: ORRP favorably affects the long-term natural history of LUTS. The
long-term economic and quality of life benefits of ORRP on LUTS should inform the
risks and benefits of RP for treatment of localized prostate cancer.
PMID- 29953884
TI - The salivary testosterone response to a chance-determined contest is associated
with face-gazing behaviours in athletic women.
AB - Human gaze is an important indicator of dominant and submissive behaviours
related to positioning in a social hierarchy. This study investigated face gazing
after a chance-determined contest and its linkage to salivary testosterone (sal
T) reactivity in athletic women. Twenty-six women athletes completed a coin-toss
game on days 7 (D7), 14 (D14) and 21 (D21) of a single menstrual cycle. The game
was played against an unknown opponent of similar age with the winner
congratulated and rewarded with all coins. Gazing towards an opponent's head or
face was timed after each contest (over 2 min) from video footage. Salivary T
(sal-T) was assessed before and 15 min after these contests. The sal-T residuals
increased after winning and decreased after losing on D7, D14 and D21 (p < 0.05).
Gaze times were longer after a loss (M = 7.8 s) than a win (M = 3.1 s) across all
days. Regression analyses revealed that the sal-T residuals and contest outcome
interacted to predict gaze time. Upon deconstruction we found that, when losing a
contest, a larger sal-T response (i.e., smaller decline) predicted a longer gaze
(beta = 1.71, p = 0.004), but no association was evident when winning (beta =
0.06, p = 0.821), and these slope patterns differed (p = 0.011). In conclusion,
winning a contest by chance increased sal-T responsivity and decreased opponent
gaze across the menstrual cycle. A positive relationship between individual sal-T
reactivity and gaze duration was observed, but only when losing. These
preliminary results support suggestions that women's T may help modulate post
competition behaviours (e.g., face gazing) possibly to achieve social cohesion
and cooperation.
PMID- 29953885
TI - Cortisol during adolescence organises personality traits and behavioural
syndromes.
AB - Despite the growing evidence for the importance of developmental experiences
shaping consistent individual differences in behaviour and physiology, the role
of endocrine factors underlying the development and maintenance of such
differences across multiple traits, remains poorly understood. Here, we
investigated how an experimental manipulation of circulating glucocorticoids
during early adolescence affects behavioural and physiological variation and
covariation later in life in the precocial cavy (Cavia aperea). Plasma cortisol
concentrations were experimentally elevated by administering cortisol via food
for 3 weeks. Struggle docility, escape latency, boldness, exploration and social
behaviour were then tested three times after individuals attained sexual
maturity. In addition, blood samples were taken repeatedly to monitor circulating
cortisol concentrations. Exogenous cortisol affected mean trait expression of
plasma cortisol levels, struggle docility and escape latency. Repeatability of
cortisol and escape latency was increased and repeatability of struggle docility
tended to be higher (approaching significance) in treated individuals. Increased
repeatability was mainly caused by an increase of among-individual variance.
Correlations among docility, escape latency and cortisol were stronger in treated
animals compared to control animals. These results suggest that exposure to
elevated levels of cortisol during adolescence can alter animal personality
traits as well as behavioural syndromes. Social and risk-taking traits showed no
correlation with cortisol levels and were unaffected by the experimental
manipulation, indicating behavioural modularity. Taken together, our data
highlight that cortisol can have organising effects during adolescence on the
development of personality traits and behavioural syndromes, adding to the
increasing evidence that not only early life but also adolescence is an important
sensitive period for behavioural development.
PMID- 29953886
TI - (2R,6R)-hydroxynorketamine rescues chronic stress-induced depression-like
behavior through its actions in the midbrain periaqueductal gray.
AB - It has been widely reported that ketamine rescues chronic stress-induced
depression-like behavior, but the underlying cellular mechanisms of the rapid
antidepressant actions of ketamine remain largely unclear. Both male and female
Sprague-Dawley rats were used and received modified learned helplessness paradigm
to induce depression-like behavior. Depression-like behavior was assayed and
manipulated using forced swim tests, sucrose preference tests and pharmacological
microinjection. We conducted whole-cell patch-clamp electrophysiological
recordings in the midbrain ventrolateral periaqueductal gray (vlPAG) neurons.
Surface and cytosolic glutamate receptor 1 (GluR1) alpha-amino-3-hydroxy-5-methyl
4-isoxazolepropionic acid (AMPA) receptor expression were analyzed using Western
blotting. Phosphorylated GluR1 expression was quantified using Western blotting
analysis. The results showed that a single systemic administration of a ketamine
metabolite (2R,6R)-hydroxynorketamine (2R,6R-HNK) rapidly rescued chronic stress
induced depression-like behavior and persisted for up to 21 days. Consistently,
the chronic stress-induced diminished glutamatergic transmission and surface
GluR1 expression in the vlPAG were also reversed by a single systemic injection
of (2R,6R)-HNK. Furthermore, bath application of (2R,6R)-HNK increased the
frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in
the vlPAG. Further evidence for the antidepressant action of (2R,6R)-HNK is
provided by the finding that microinjection of (2R,6R)-HNK into the vlPAG
exhibited a rapid-acting and long-lasting antidepressant effect. This
antidepressant effect of (2R,6R)-HNK was prevented by the intra-vlPAG
microinjection of AMPA receptor antagonist CNQX. Together, the current results
provide evidence that (2R,6R)-HNK rescues chronic stress-induced depression-like
behavior with rapid-acting and long-lasting antidepressant effects through
enhancement of AMPA receptor-mediated transmission in the vlPAG.
PMID- 29953887
TI - Altered salt taste response and increased tongue epithelium Scnna1 expression in
adult Engrailed-2 null mice.
AB - Sensory impairments are critical for diagnosing and characterizing
neurodevelopmental disorders. Taste is a sensory modality often not well
characterized. Engrailed-2 (En2) is a transcription factor critical for neural
development, and mice lacking En2 (En2-/-) display signs of impaired social
interaction, cognitive processes (e.g., learning and memory, conditioned fear),
and neurodevelopmental alterations. As such, En2-/- mice display the behavioral
deficits and neural impairments characteristic of the core symptoms associated
with autism spectrum disorder (ASD). The objective of this study was to
characterize the taste function in En2-/- compared with En2+/+ in adult male
mice. Measuring taste responsiveness by an automated gustometer, En2 null mice
had decreased lick responses for 1.6 M fructose, whereas they demonstrated an
increased taste responsivity (i.e., relative to water) at 0.3 M sodium chloride
and 1 M monosodium glutamate. In a separate cohort of mice, En2-/- mice had an
increased preference for sodium chloride over a range of concentrations (0.032
0.3 M) compared with En2+/+ mice. Regional gene expression of the tongue
epithelium demonstrated an increase in Scnn1a, T2R140, T1R3, and Trpm5 and a
decrease in Pkd1l3 in En2 null mice. Taken together, such data indicate that
deficits in En2 can produce sensory impairments that can have a measurable impact
on taste, particularly salt taste.
PMID- 29953888
TI - The Dual Role of the 2'-OH Group of A76 tRNATyr in the Prevention of d-tyrosine
Mistranslation.
AB - Aminoacyl-tRNA-synthetases are crucial enzymes for initiation step of
translation. Possessing editing activity, they protect living cells from
misincorporation of non-cognate and non-proteinogenic amino acids into proteins.
Tyrosyl-tRNA synthetase (TyrRS) does not have such editing properties, but it
shares weak stereospecificity in recognition of d-/l-tyrosine (Tyr).
Nevertheless, an additional enzyme, d-aminoacyl-tRNA-deacylase (DTD), exists to
overcome these deficiencies. The precise catalytic role of hydroxyl groups of the
tRNATyr A76 in the catalysis by TyrRS and DTD remained unknown. To address this
issue, [32P]-labeled tRNATyr substrates have been tested in aminoacylation and
deacylation assays. TyrRS demonstrates similar activity in charging the 2' and 3'
OH groups of A76 with l-Tyr. This synthetase can effectively use both OH groups
as primary sites for aminoacylation with l-Tyr, but demonstrates severe
preference toward 2'-OH, in charging with d-Tyr. In both cases, the catalysis is
not substrate-assisted: neither the 2'-OH nor the 3'-OH group assists catalysis.
In contrast, DTD catalyzes deacylation of d-Tyr-tRNATyr specifically from the 3'
OH group, while the 2'-OH assists in this hydrolysis.
PMID- 29953889
TI - Conglomeration of novel Culex quinquefasciatus salivary proteins to contrive
multi-epitope subunit vaccine against infections caused by blood imbibing
transmitter.
AB - The southern house vector, Culex quinquefasciatus is the paramount cause of
Japanese encephalitis, West Nile fever and Lymphatic Filariasis, which is
globally affecting the worldwide population. Many attempts were made by
researchers with different perceptions to discover regimen against these
aforementioned ailments but the output was not that effectual. Consequently,
there is an imminent need to develop very effective and potential treatment
against these perilous diseases. Employing immunoinformatic approaches, we have
designed the multi-epitope subunit vaccine by exploring salivary proteins of
Culex quinquefasciatus, which possess both antigenic and potent immunogenic
behaviour. The immunogenic epitopes from the immune cells (B-cell, CTL, and HTL)
were predicted and linked together with the help of linkers. Apart from this, at
the N-terminal of the construct, an adjuvant was added in order to enhance the
immunogenicity of the vaccine. The physiological parameters, antigenicity and
allergenicity were also evaluated for the designed vaccine construct. Molecular
docking between ligand (vaccine construct) and TLR-4 receptor was performed.
Molecular dynamics simulation of the docked complex was performed to identify the
stability, patterns, macromolecules interactions and their behaviour. Finally, to
ensure the translation and gene expression efficiency of designed construct,
insilico restriction cloning was executed into suitable expression vector pET28a.
PMID- 29953890
TI - Structure characterization of one polysaccharide from Lepidium meyenii Walp., and
its antioxidant activity and protective effect against H2O2-induced injury
RAW264.7 cells.
AB - The structural characterization, antioxidant activity and protective effect
against H2O2-induced injury RAW264.7 cells of a new polysaccharide (MP1) isolated
from Lepidium meyenii Walp. were investigated. The molecular weight was estimated
to be 4.67 * 105 Da by HPLC-ELSD analysis. Monosaccharide composition was
determined to be arabinose and galactose in a molar ratio of 2:1 by GC-MS and PMP
HPLC-UV analysis. Methylation combined with 1D and 2D NMR spectrum analysis
revealed that MP1 was an arabinogalactan. MP1 possessed a moderate antioxidant
activity in vitro in DPPH, ABTS, superoxide and hydroxyl radicals scavenging,
Fe2+ chelating, lipid peroxidation inhibition and reducing power assays. MP1
could also effectively protect RAW264.7 cells from H2O2-induced injury by
maintaining stable cell viability, decreasing ROS, MDA and LDH level and
enhancing SOD, GSH-Px and CAT activity. These results suggested the potential
utilization of MP1 as a natural antioxidant for food and pharmaceutical
applications.
PMID- 29953891
TI - Importance of the hydroxyl substituents in the B-ring of plant flavonols on their
preferential binding interactions with VEGF G-quadruplex DNA: Multi-spectroscopic
and molecular modeling studies.
AB - G-quadruplex (G4) structures are known to be promising anticancer drug targets
and flavonols (an important class of flavonoids) are small molecules reported to
possess several health-promoting properties including those of anticancer
activities. In this work, we explored the interactions of the structurally
related plant flavonols kaempferol (KAE; 3,5,7,4'OH flavone) and morin (MOR;
3,5,7,2',4'OH flavone) with various G4-DNA sequences along with duplex DNA using
a combination of spectroscopic and molecular docking studies. Our results
revealed that KAE shows preferential interaction with VEGF G4-DNA in comparison
to the other G4 sequences and duplex DNA. Moreover, KAE enhances the thermal
stability of VEGF G4-DNA. In contrast, MOR exhibits an appreciably weaker level
of interaction with both duplex and various G4-DNAs, with no significant
structural specificity. The contrasting DNA binding behaviors suggest a crucial
role of the 2'OH substituent in the B-ring of flavonol moiety. While KAE is
relatively planar, MOR adopts a significantly non-planar conformation
attributable to steric hindrance from the additional 2'OH substituent. This small
structural difference is apparently very important for the ability of KAE and MOR
to interact with VEGF G4-DNA. Thus, KAE (but not MOR) appears to be an effective
ligand for VEGF G4-DNA, opening up possibilities of its application for
regulation of gene expression in cancer cells.
PMID- 29953892
TI - Simultaneous biosensing of CA125 and CA15-3 tumor markers and imaging of OVCAR-3
and MCF-7 cells lines via bi-color FRET phenomenon using dual blue-green
luminescent carbon dots with single excitation wavelength.
AB - Here, we developed a facile route to synthesize two CDs with the maximum emission
locates at 326 nm and 443 nm under 230 nm excitation. The absolute
photoluminescence quantum yield (QY) is as high as 29% and 52% for CD-1 and CD-2
with strong blue-green fluorescence, respectively. The functionalized CDs (CDs
NH2, CDs-COOH) conjugated with antibodies used for simultaneous detection of two
tumor-markers using fluorescence resonance energy transfer (FRET) strategy, when
MoS2 nanosheets functionalized with ssDNA related aptamers applied as quencher.
The response of sensor enhanced gradually with increasing of targets at range
0.05-8 pg/mL with detection limit (DL) 5.0 fg/mL for CA125, while for CA15-3
concentration range was 1.0-35 pg/mL and DL was 0.5 pg/mL. This strategy revealed
a stable analytical performance for the detection of OVCAR-3 and MCF-7 cells
lines ranging from 1000 to 10,000 cells/mL with DL 2-3 cells in 10 MUL of
injected sample. When the CDs-Ab was used in selective imaging of MCF-7 and OVCAR
3 cancer cells, a strong PL emission was observed. After incubation times, both
the cells size and shape clearly remained without any change. The results
demonstrate that the CDs are a potentially excellent bioimaging component in
pathological diagnosis, biomedicine research and management of cancer diseases.
PMID- 29953893
TI - Cholesterol-grafted chitosan micelles as a nanocarrier system for drug-siRNA co
delivery to the lung cancer cells.
AB - Combined delivery of a therapeutic small interfering RNA (siRNA) and a
chemotherapeutic agent to cancer cells is promising as anticancer therapy, which
could offer enhanced cell killing potential and low side effect. However,
simultaneous delivery to tumor is challenging. In our study, cholesterol-modified
low molecular weight chitosan (MW ~ 15 kDa) was employed as a self-assembled
delivery system for both siRNA and a hydrophobic chemotherapeutic agent, curcumin
to cancer cells. The siRNA/curcumin loaded nanoparticles (C-CCM/siRNA) were
physico-chemically characterized for particle size (165 +/- 2.6 nm) and zeta
potential (+24.8 +/- 2.2 mV). The ability of CCM to condense siRNA was determined
by ethidium bromide exclusion and gel retardation assay using electrophoresis.
The result demonstrated that the condensation of C-CCM with siRNA was optimum at
minimum N/P ratio of 40. C-CCM/siRNA was stable at 4 degrees C for a period of
>1 month. C-CCM/siRNA was taken up efficiently by human lung carcinoma cells,
A549 in a time-dependent manner. The cellular internalization of C-CCM/siRNA was
observed via clathrin-mediated endocytosis as determined by using specific
endocytosis inhibitors. The study demonstrated the feasibility of the use of
cholesterol conjugated chitosan as a co-delivery system for both siRNA and a
hydrophobic drug for combination cancer therapy.
PMID- 29953894
TI - Clinicopathological and prognostic significance of SHP2 and Hook1 expression in
patients with thyroid carcinoma.
AB - Some thyroid carcinomas (TCs) have an aggressive biological behavior and poor
prognosis, and lacking of effective molecular markers is still the main obstacle
for clinical stratified diagnosis and treatment of TC. The aim of the study was
to discover the clinicopathological and prognostic implications of Src homology
region 2-containing protein tyrosine phosphatase 2 (SHP2) and Hook microtubule
tethering protein 1 (Hook1) expression in TC. The expression of SHP2 and Hook1
was detected by immunohistochemistry on tissue microarrays from 313 primary TCs
who underwent surgery in January 2006 and January 2010 in Zhejiang Cancer
Hospital. The chi2 test, Kaplan-Meier method, and Cox proportional-hazards
regression models were used to analyze the associations between their expressions
and clinicopathological features and prognosis. The expression rates of SHP2 and
Hook1 in TC were 57.5% (180/313) and 22.0% (69/313), respectively. SHP2 was
positively correlated with Hook1 in TC. SHP2 expression differed significantly by
age, histologic variants, maximal tumor diameter, intrathyroidal dissemination,
metastases, and disease stage (P < .05). Moreover, patients with high SHP2
expression had reduced risk for death of disease compared with those with low
SHP2 expression (hazard ratio, 0.267; 95% confidence interval, 0.105-0.684; P =
.006) in univariate analysis, but that multivariate analysis failed to suggest
that SHP2 was an independent prognostic factor. Hook1 expression differed
significantly by histologic variants, maximal tumor diameter, and intrathyroidal
dissemination (P < .05). However, there was no significant correlation between
Hook1 expression and outcome in TC (P > .05). Our results suggested that SHP2 may
be a favorable indicator of prognosis in TC.
PMID- 29953895
TI - Coexpression of CDX2 and CK20 in hepatocellular carcinoma, an exceedingly rare co
incidence with potential diagnostic pitfall.
PMID- 29953896
TI - Temporal small arterial inflammation is common in patients with giant cell
arteritis.
AB - Giant cell arteritis (GCA) primarily involves medium-to-large arteries. Small
vessel inflammation is a recognized phenomenon occurring in association with GCA.
However, its significance is poorly elucidated. Histologic sections and medical
records of105 temporal artery specimens were retrospectively reviewed between
2008 and 2017 to examine associated clinical manifestations and laboratory data
including antinuclear antibody and p-antineutrophilic cytoplasmic antibody
titers. Immunohistochemical staining for CD4 and CD8 was performed in select
cases to assess the nature of the inflammatory response. Seventy-eight patients
meeting the diagnostic criteria of temporal arteritis were included in the
analysis. Twenty-eight specimens demonstrated temporal arteritis with small
arterial inflammation (SAI), and 50 specimens showed temporal arteritis without
SAI. Eight (28.6%) of 28 patients with SAI presented with jaw claudication,
whereas 5 (17.9%) were febrile at presentation. In contrast, in 50 patients
without SAI, jaw claudication and fever were seen in 11 and 2 cases, respectively
(P = .01 and P = .0047, respectively). No statistically significant difference
was noted between other symptoms and laboratory indices between the 2 groups.
Elevated p-antineutrophilic cytoplasmic antibody titers in GCA may be associated
with concomitant polymyalgia rheumatica or treatment-resistant disease. We also
identified a higher count of CD4 and CD8 T cells in SAI cases, although the ratio
of CD4/CD8 T lymphocytes was within normal limits. In conclusion, simultaneous
involvement of arterioles and medium- to large-sized arteries is common in GCA
and may be associated with treatment-refractory disease. Documentation of small
arterial involvement in GCA will help the clinicians to manage the disease more
effectively.
PMID- 29953897
TI - Leveraging technology to promote smoking cessation in urban and rural primary
care medical offices.
AB - We examined the use of automated voice recognition (AVR) messages targeting
smokers from primary care practices located in underserved urban and rural
communities to promote smoking cessation. We partnered with urban and rural
primary care medical offices (n = 7) interested in offering this service to
patients. Current smokers, 18 years and older, who had completed an office visit
within the previous 12 months, from these sites were used to create a smoker's
registry. Smokers were recruited within an eight county region of western New
York State between June 2012 and August 2013. Participants were contacted over
six month intervals using the AVR system. Among 5812 smokers accrued 1899 (32%)
were reached through the AVR system and 55% (n = 1049) continued to receive
calls. Smokers with race other than white or African American were less likely to
be reached (OR = 0.71, 0.57-0.90), while smokers ages 40 and over were more
likely to be reached. Females (OR = 0.78, 0.65-0.95) and persons over age 40
years were less likely to opt out, while rural smokers were more likely to opt
out (OR = 3.84, 3.01-4.90). Among those receiving AVR calls, 30% reported smoke
free (self-reported abstinence over a 24 h period) at last contact; smokers from
rural areas were more likely to report being smoke free (OR = 1.41, 1.01-1.97).
An AVR-based smoking cessation intervention provided added value beyond typical
tobacco cessation efforts available in these primary care offices. This
intervention required no additional clinical staff time and served to satisfy a
component of patient center medical home requirements for practices.
PMID- 29953898
TI - Breastfeeding and later maternal risk of hypertension and cardiovascular disease
The role of overall and abdominal obesity.
AB - In this study, we examined how any, full, and partial breastfeeding durations
were associated with maternal risk of hypertension and cardiovascular disease
(CVD), and how prepregnancy body mass index (BMI) and waist circumference 7 years
postpartum influenced these associations. A total of 63,260 women with live-born
singleton infants in the Danish National Birth Cohort (1996-2002) were included.
Interviews during pregnancy and 6 and 18 months postpartum provided information
on prepregnancy weight, height, and the duration of full and partial
breastfeeding. Waist circumference was self-reported 7 years postpartum. Cox
regression models were used to estimate hazard ratios of incident hypertension
and CVD, registered in the National Patient Register from either 18 months or 7
years postpartum through 15 years postpartum. Any breastfeeding >=4 months was
associated with 20-30% lower risks of hypertension and CVD compared to <4 months
in both normal/underweight and overweight/obese women. At follow-up starting 7
years postpartum, similar risk reductions were observed after accounting for
waist circumference adjusted for BMI. Partial breastfeeding >2 months compared to
<=2 months, following up to 6 months of full breastfeeding, was associated with
10-25% lower risk of hypertension and CVD. Compared with short breastfeeding
duration, additional partial breastfeeding was as important as additional full
breastfeeding in reducing risk of hypertension and CVD. Altogether, longer
duration of breastfeeding was associated with lower maternal risk of hypertension
and CVD irrespective of prepregnancy BMI and abdominal adiposity 7 years after
delivery. Both full and partial breastfeeding contributed to an improved
cardiovascular health in mothers.
PMID- 29953899
TI - More than fishing for a cure: The promises and pitfalls of high throughput cancer
cell line screens.
AB - High-throughput screens in cancer cell lines (CCLs) have been used for decades to
help researchers identify compounds with the potential to improve the treatment
of cancer and, more recently, to identify genomic susceptibilities in cancer via
genome-wide shRNA and CRISPR/Cas9 screens. Additionally, rich genomic and
transcriptomic data of these CCLs has allowed researchers to pair this screening
data with biological features, enabling efforts to identify biomarkers of
treatment response and gene dependencies. In this paper, we review the major CCL
screening efforts and the large datasets these screens have made available. We
also assess the CCL screens collectively and include a resource with harmonized
CCL and compound identifiers to facilitate comparisons across screens. The CCLs
in these screens were found to represent a wide range of cancer types, with a
strong correlation between the representation of a cancer type and its associated
mortality. Patient ages and gender distributions of CCLs were generally as
expected, with some notable exceptions of female underrepresentation in certain
disease types. Also, ethnicity information, while largely incomplete, suggests
that African American and Hispanic patients may be severely underrepresented in
these screens. Nearly all genes were targeted in the genetic perturbations
screens, but the compounds used for the drug screens target less than half of
known cancer drivers, likely reflecting known limitations in our drug design
capabilities. Finally, we discuss recent developments in the field and the
promise they hold for enabling future screens to overcome previous limitations
and lead to new breakthroughs in cancer treatment.
PMID- 29953900
TI - Neurosteroids: non-genomic pathways in neuroplasticity and involvement in
neurological diseases.
AB - Neurosteroids are neuroactive brain-born steroids. They can act through non
genomic and/or through genomic pathways. Genomic pathways are largely described
for steroid hormones: the binding to nuclear receptors leads to transcription
regulation. Pregnenolone, Dehydroepiandrosterone, their respective sulfate esters
and Allopregnanolone have no corresponding nuclear receptor identified so far
whereas some of their non-genomic targets have been identified. Neuroplasticity
is the capacity that neuronal networks have to change their structure and
function in response to biological and/or environmental signals; it is regulated
by several mechanisms, including those that involve neurosteroids. In this
review, after a description of their biosynthesis, the effects of Pregnenolone,
Dehydroepiandrosterone, their respective sulfate esters and Allopregnanolone on
their targets will be exposed. We then shall highlight that neurosteroids, by
acting on these targets, can regulate neurogenesis, structural and functional
plasticity. Finally, we will discuss the therapeutic potential of neurosteroids
in the pathophysiology of neurological diseases in which alterations of
neuroplasticity are associated with changes in neurosteroid levels.
PMID- 29953901
TI - Novel therapeutic strategy for cancer and autoimmune conditions: Modulating cell
metabolism and redox capacity.
AB - Dysregulation of cell metabolism and redox balance is implicated in the
pathogenesis and progression of cancer and autoimmune diseases. Because the cell
proliferation and apoptotic regulatory pathways are interconnected with metabolic
and redox signalling pathways, the current mono-target treatment is ineffective,
and multi-drug resistance remains common. Complex diseases are often implicated
in a network-based context of pathology; therefore, a new holistic intervention
approach is required to block multi-crosstalk in such complicated circumstances.
The use of therapeutic agents isolated from herbs to holistically modulate
metabolism and redox state has been shown to relieve carcinoma growth and the
inflammatory response in autoimmune disorders. Multiple clinically applied or
novel herbal chemicals with metabolic and redox modulatory capacity as well as
low toxicity have recently been identified. Moreover, new metabolic targets and
mechanisms of drug action have been discovered, leading to the exploration of new
pathways for drug repositioning, clinical biomarker spectra, clinical treatment
strategies and drug development. Taken together with multiple supporting
examples, the modulation of cell metabolism and the redox capacity using herbal
chemicals is emerging as a new, alternative strategy for the holistic treatment
of cancer and autoimmune disorders. In the future, the development of new
diagnostic tools based on the detection of metabolic and redox biomarkers,
reformulation of optimized herbal compositions using artificial intelligence, and
the combination of herbs with mono-targeting drugs will reveal new potential for
clinical application.
PMID- 29953902
TI - Molecular targets of atypical antipsychotics: From mechanism of action to
clinical differences.
AB - The introduction of atypical antipsychotics (AAPs) since the discovery of its
prototypical drug clozapine has been a revolutionary pharmacological step for
treating psychotic patients as these allow a significant recovery not only in
terms of hospitalization and reduction in symptoms severity, but also in terms of
safety, socialization and better rehabilitation in the society. Regarding the
mechanism of action, AAPs are weak D2 receptor antagonists and they act beyond D2
antagonism, involving other receptor targets which regulate dopamine and other
neurotransmitters. Consequently, AAPs present a significant reduction of
deleterious side effects like parkinsonism, hyperprolactinemia, apathy and
anhedonia, which are all linked to the strong blockade of D2 receptors. This
review revisits previous and current findings within the class of AAPs and
highlights the differences in terms of receptor properties and clinical
activities among them. Furthermore, we propose a continuum spectrum of "atypia"
that begins with risperidone (the least atypical) to clozapine (the most
atypical), while all the other AAPs fall within the extremes of this spectrum.
Clozapine is still considered the gold standard in refractory schizophrenia and
in psychoses present in Parkinson's disease, though it has been associated with
adverse effects like agranulocytosis (0.7%) and weight gain, pushing the
scientific community to find new drugs as effective as clozapine, but devoid of
its side effects. To achieve this, it is therefore imperative to characterize and
compare in depth the very complex molecular profile of AAPs. We also introduce
relatively new concepts like biased agonism, receptor dimerization and
neurogenesis to identify better the old and new hallmarks of "atypia". Finally, a
detailed confrontation of clinical differences among the AAPs is presented,
especially in relation to their molecular targets, and new means like therapeutic
drug monitoring are also proposed to improve the effectiveness of AAPs in
clinical practice.
PMID- 29953903
TI - FAAH inhibition attenuates TLR3-mediated hyperthermia, nociceptive- and anxiety
like behaviour in female rats.
AB - Aberrant activation of toll-like receptor (TLR)s results in persistent and
prolonged neuroinflammation and has been implicated in the pathogenesis and
exacerbation of psychiatric and neurodegenerative disorders. TLR3 coordinates the
innate immune response to viral infection and recent data have demonstrated that
inhibiting fatty acid amide hydrolase (FAAH), the enzyme that primarily
metabolizes anandamide, modulates TLR3-mediated neuroinflammation. However, the
physiological and behavioural consequences of such modulation are unknown. The
present study examined the effect of URB597, a selective FAAH inhibitor, on
neuroinflammation, physiological and behavioural alterations following
administration of the TLR3 agonist and viral mimetic poly I:C to female rats.
URB597 attenuated TLR3-mediated fever, mechanical and cold allodynia, and anxiety
like behaviour in the elevated plus maze and open field arena. There was no
effect of URB597 on TLR3-mediated decreases in body weight and no effect in the
sucrose preference or forced swim tests. URB597 attenuated the TLR3-mediated
increase in the expression of CD11b and CD68, markers of microglia/macrophage
activation. In summary, these data demonstrate that enhancing FAAH substrate
levels suppresses TLR3-mediated microglia/macrophage activation and associated
changes in fever, nociceptive responding and anxiety-related behaviour. These
data provide further support for FAAH as a novel therapeutic target for
neuroinflammatory disorders.
PMID- 29953904
TI - Increased training compensates for OX1R blockage-impairment of spatial memory and
c-Fos expression in different cortical and subcortical areas.
AB - It has been suggested that the orexin system modulates learning and memory
related processes. However, the possible influence that training could have on
the effect of the blockade of orexin-A selective receptor (OX1R) on a spatial
memory task has not been explored. Therefore, the present study attempts to
compare the effects of OX1R antagonist SB-334867 infusion on spatial memory in
two different conditions in the Morris Water Maze (MWM). This experiment
evaluated the animals' performance in weak training (2 trials per session) vs
strong training (6 trials per session) protocols in a spatial version of the MWM.
We found that in the 2-trial condition the post-training SB-334867 infusion had a
negative effect on consolidation as well as on the retention and reversal
learning of the task 72 h later. This effect was not apparent in the 6-trial
condition. In addition, while the strong training groups showed a general
increase in c-Fos expression in several brain areas of the hippocampal-thalamic
cortical circuit, SB-334867 administration had the opposite effect in areas that
have been previously reported to have a high density of OX1R. Specifically, the
SB-infused group in the 2-trial condition showed a decrease in c-Fos
immunoreactivity in the dentate gyrus, granular retrosplenial and prelimbic
cortices, and centrolateral thalamic nucleus. This was not observed for subjects
in the 6-trial condition. The activation of these areas could constitute a
neuroanatomical substrate involved in the compensatory mechanisms of training
upon SB-334867 impairing effects on a MWM spatial task.
PMID- 29953906
TI - Auditory neglect in children following perinatal stroke.
AB - Auditory neglect has been found in adults with right hemisphere focal brain
lesions following strokes. Visual and tactile neglect has been found in children
following both left and right hemisphere lesions resulting from perinatal
strokes. The present cross-sectional study assessed auditory neglect in children
with early unilateral brain damage from perinatal stroke. Twenty-six children
with perinatal stroke and matched controls participated. All were asked to
identify the location of a pure tone presented in left or right auditory fields.
We found that children who had experienced left hemisphere perinatal strokes were
significantly better at localizing sounds on the left side of space than the
right side of space, and that response times improved with age on a normal
trajectory relative to controls in left hemispace, while they did not improve
normally in right hemispace. Children with right hemisphere perinatal strokes
were significantly worse at localizing sounds on the right side of space relative
to typically developing controls, and did not follow control trajectories for
improvement in response times on the left or the right sides of space. Our
preliminary results suggest that left hemisphere perinatal strokes may result in
contralateral auditory neglect, while right hemisphere perinatal strokes may
result in bilateral auditory neglect. Neglect was more severe in children with
parietal lobe involvement, suggesting that the parietal lobe may play a dominant
role in auditory attention in the developing brain.
PMID- 29953905
TI - NMDA receptor GluN2A subunit deletion protects against dependence-like ethanol
drinking.
AB - The N-methyl-D-aspartate receptor (NMDAR) is mechanistically involved in the
behavioral and neurophysiological effects of alcohol, but the specific role of
the GluN2A subunit remains unclear. Here, we exposed mice with constitutive
GluN2A gene knockout (KO) to chronic intermittent ethanol vapor (CIE) and tested
for EtOH consumption/preference using a two-bottle choice paradigm, as well as
NMDAR-mediated transmission at basolateral amygdala synapses via ex vivo slice
electrophysiology. Results showed that GluN2A KO mice attained comparable blood
EtOH levels in response to CIE exposure, but did not exhibit the significant
increase in EtOH drinking that was observed in CIE-exposed wildtypes. GluN2A KO
mice also showed no alterations in BLA NMDAR-mediated synaptic transmission after
CIE, relative to air-exposed, whereas C57BL/6 J mice showed an attenuated
synaptic response to GluN2B antagonism. Taken together, these data add to
mounting evidence supporting GluN2A-containing NMDARs as a mechanism underlying
relative risk for developing EtOH dependence after repeated EtOH exposure.
PMID- 29953907
TI - Mechanism of nitric oxide and acid-sensing ion channel 1a modulation of panic
like behaviour in the dorsal periaqueductal grey of the mouse.
AB - Predators induce defensive responses and fear behaviours in prey. The rat
exposure test (RET) is frequently used as an animal model of panic. Nitric oxide
(NO) which has been reported to be activated by the NMDA receptor, in turn
mediates calcium/calmodulin-dependent protein kinase II (CaMKII) signalling
pathways in defensive responses. ACCN2, the orthologous human gene of acid
sensing ion channel 1a (ASIC1a), is also associated with panic disorder; however,
few studies have focused on the role of ASIC1a in the modulation of panic and
calcium/CaMKII signalling by NO. In the present study, NG-nitro-L-arginine-methyl
ester (L-NAME; non-selective NOS inhibitor), S-nitroso-N-acetyl-D,L-penicillamine
(SNAP; NO donor), and psalmotoxin (PcTx-1; selective ASIC1a blocker) were
administered to the dorsal periaqueductal grey (dPAG) before the predator
stimulus, and the roles of NO in the expression of ASIC1a, phosphorylation of
CaMKIIalpha (p-CaMKIIalpha) and expression of calmodulin (CaM) were investigated.
The effects of ASIC1a, p-CaMKIIalpha and CaM regulation were also examined. Our
results showed that intra-dPAG infusion of L-NAME weakened panic-like behaviour
and decreased ASIC1a, p-CaMKIIalpha and CaM expression levels, whereas intra-dPAG
infusion of SNAP enhanced panic-like behaviour and increased ASIC1a, p
CaMKIIalpha and CaM levels. Intra-dPAG infusion of PcTx-1 also weakened panic
like behaviour and decreased p-CaMKIIalpha expression level. Taken together,
these results indicate that NO and ASIC1a are involved in the modulation of RET
induced panic-like behaviour in the dPAG. NO regulates the calcium/CaMKII
signalling pathways, and ASIC1a participates in this regulation.
PMID- 29953909
TI - Mechanical CPR in a new light: A new approach to the analyses of resuscitation
studies.
PMID- 29953908
TI - Masking Differentially Affects Envelope-following Responses in Young and Aged
Animals.
AB - Age-related hearing decline typically includes threshold shifts as well as
reduced wave I auditory brainstem response (ABR) amplitudes due to cochlear
synaptopathy/neuropathy, which may compromise precise coding of suprathreshold
speech envelopes. This is supported by findings with older listeners, who have
difficulties in envelope and speech processing, especially in noise. However,
separating the effects of threshold elevation, synaptopathy, and degradation by
noise on physiological representations may be difficult. In the present study,
the effects of notched, low- and high-pass noise on envelope-following responses
(EFRs) in aging were compared when sound levels (aged: 85-dB SPL; young: 60- to
80-dB SPL) were matched between groups peripherally, by matching wave I ABR
amplitudes, or centrally by matching EFR amplitudes. Low-level notched noise
reduced EFRs to sinusoidally amplitude-modulated (SAM) tones in young animals for
notch widths up to 2 octaves. High-pass noise above the carrier frequency reduced
EFRs. Young animals showed EFR reductions at lower noise levels. Low-pass noise
did not reduce EFRs in either young or aged animals. High-pass noise may affect
EFR amplitudes in young animals more than aged by reducing the contributions of
high-frequency-sensitive inputs. EFRs to SAM tones in modulated noise (NAM)
suggest that neurons of young animals can synchronize to NAM at lower sound
levels and maintain dual AM representations better than older animals. The
overall results show that EFR amplitudes are strongly influenced by aging and the
presence of a competing sound that likely reduces or shifts the pool of
responsive neurons.
PMID- 29953910
TI - In Silico Trial of MR-Guided Midtreatment Adaptive Planning for Hypofractionated
Stereotactic Radiation Therapy in Centrally Located Thoracic Tumors.
AB - PURPOSE: Hypofractionated (>5 fraction) stereotactic radiation therapy (HSRT) may
allow for ablative biologically equivalent dose to tumors with a lower risk of
organ-at-risk (OAR) toxicity in central thoracic tumors. Adaptive planning may
further improve OAR sparing while maintaining planning target volume (PTV)
coverage. We hypothesized that midtreatment adaptive replanning would offer
dosimetric advantages during HSRT for central thorax malignancies using magnetic
resonance imaging (MRI)-guided radiation therapy. METHODS AND MATERIALS: Twelve
patients with central thorax tumors received HSRT using MRI-guided radiation
therapy. Clinically delivered regimens were 60 Gy in 12 fractions or 62.5 Gy in
10 fractions, with low-field magnetic resonance (0.35 T) volumetric setup imaging
acquired at each fraction. Daily gross tumor volume (GTV) and OARs were
retrospectively redefined on fraction 1, 6, and 10 MRIs, and GTV response was
recorded. Simulated initial plans prescribed a dose of 60 Gy in 12 fractions
based on fraction 1 MRI. Midtreatment adaptive plans were created based on
fraction 6 anatomy-of-the-day. All plans were created using an isotoxicity
approach with a goal of 95% PTV coverage, subject to hard OAR constraints, to
represent clinically ideal OAR sparing. Plans were then compared for projected
OAR sparing and PTV coverage. RESULTS: Patients demonstrated significant on
treatment MRI-defined GTV reduction (median 41.8%; range 16.7%-65.7%). At
fraction 6, median reduction was 26.7%. All initial plans met OAR constraints.
Initial plan application to fraction 6 and fraction 10 anatomy resulted in 8 OAR
violations (5 of 13 patients) and 10 OAR violations (6 of 13 patients). All
fraction 6 violations persisted at fraction 10. Midpoint adaptive planning
reversed 100% of midpoint OAR violations and tended to reduce the magnitude of
OAR violations incurred at fraction 10. In 40% of fractions (2 of 5) in which OAR
violation resulted from initial plan application to fraction 6 anatomy, PTV
coverage was increased concomitant with violation reversal. CONCLUSIONS:
Midtreatment adaptive planning based on tumor response may be dosimetrically
advantageous for sparing of surrounding critical structures in HSRT for central
thorax malignancies and could be applied using either an online or offline
paradigm.
PMID- 29953911
TI - Changes in Brain Metastasis During Radiosurgical Planning.
AB - PURPOSE: To determine whether there are any changes in brain metastases or
resection cavity volumes between planning magnetic resonance imaging (MRI) and
radiosurgery (RS) treatment and whether these led to a change in management or
alteration in the RS plan. METHODS AND MATERIALS: Patients undergoing RS for
brain metastasis or tumor resection cavities had a standardized planning MRI (MRI
1) performed and a repeat verification MRI (MRI-2) 24 hours before RS. Any change
in management, including replanning based on MRI-2, was recorded. RESULTS: Thirty
four patients with a total of 59 lesions (44 metastases and 15 tumor resection
cavities) were assessed with a median time between MRI-1 and MRI-2 of 7 days.
Seventeen patients (50%) required a change in management based on the changes
seen on MRI-2. For patients with 7 days or less between scans, 41% (9 of 22)
required a change in management; among patients with 8 days or more between
scans, 78% (7 of 9) required a change in management. Per lesion, 32 out of 59
lesions required replanning, including 7 of 15 (47%) cavities and 25 of 44 (57%)
metastases, with the most common reason (23 lesions) being an increase in gross
target volume (tumor) or clinical target volume (tumor cavity). CONCLUSIONS:
Measurable changes occur in brain metastasis over a short amount of time, with a
change in management required in 41% of patients with 7 days between MRI-1 and
MRI-2 and in 78% of patients when there is a delay longer than 7 days. We
therefore recommend that the time between planning MRI and RS treatment be as
short as possible.
PMID- 29953913
TI - Brain endocannabinoid signaling exhibits remarkable complexity.
AB - The endocannabinoid (eCB) signaling system is one of the most extensive of the
mammalian brain. Despite the involvement of only few specific ligands and
receptors, the system encompasses a vast diversity of triggered mechanisms and
driven effects. It mediates a wide range of phenomena, including the regulation
of transmitter release, neural excitability, synaptic plasticity, impulse spread,
long-term neuronal potentiation, neurogenesis, cell death, lineage segregation,
cell migration, inflammation, oxidative stress, nociception and the sleep cycle.
It is also known to be involved in the processes of learning and memory
formation. This extensive scope of action is attained by combining numerous
variables. In a properly functioning brain, the correlations of these variables
are kept in a strictly controlled balance; however, this balance is disrupted in
many pathological conditions. However, while this balance is known to be
disrupted by drugs in the case of addicts, the stimuli and mechanisms influencing
the neurodegenerating brain remain elusive. This review examines the multiple
factors and phenomena affecting the eCB signaling system in the brain. It
evaluates techniques of controlling the eCB system to identify the obstacles in
their applications and highlights the crucial interdependent variables that may
influence biomedical research outcomes.
PMID- 29953912
TI - Threshold dynamics of the Transmission of Antibiotic-Resistant Infections.
AB - Despite numerous studies conducted, multidrug-resistant infections such as
methicillin-resistant Staphylococcus aureus (MRSE) and vancomycin-resistant
enterococci (VRE) are still increasing in hospitals, and yet continued to be the
important challenges of worldwide health. Mathematical modeling gives an
insightful information in policy and decision making to control the transmission
and spread of these infections globally. We formulated and analyse a mathematical
model to characterise the transmission co-dynamics of hospital-acquired MRSE (HA
MRSA) and community-acquired MRSE (CA-MRSA) and to investigate the long run
competitiveness of the two strains in hospital. Numerical simulations are carried
out to explore the basic reproduction numbers for the two strains so as to
determine the dominant strain in the future in hospital setting. Under some
conditions, invasion reproduction numbers are also applied to determine the
uniform persistence of the two strains. We further performed sensitivity analysis
to examine the influence of model parameters on the transmission and spread of
the the strains, thereby determine the effective intervention strategies that
reduce the overflow of the infections in hospital setting. To support theoretical
findings qualitatively, graphical representations are provided.
PMID- 29953914
TI - Endothelial cell regulation through epigenetic mechanisms: Depicting parallels
and its clinical application within an intra-islet microenvironment.
AB - The intra-islet endothelial cells (ECs), the building blocks of islet
microvasculature, govern a number of cellular and pathophysiological processes
associated with the pancreatic tissue. These cells are key to the angiogenic
process and essential for islet revascularization after transplantation.
Understanding fundamental mechanisms by which ECs regulate the angiogenic process
is important as these cells maintain and regulate the intra-islet environment
facilitated by a complex signaling crosstalk with the surrounding endocrine
cells. In recent years, many studies have demonstrated the impact of epigenetic
regulation on islet cell development and function. This review will present an
overview of the reports involving endothelial epigenetic mechanisms particularly
focusing on histone modifications which have been identified to play a critical
role in governing EC functions by modifying the chromatin structure. A better
understanding of epigenetic mechanisms by which these cells regulate gene
expression and function to orchestrate cellular physiology and pathology is
likely to offer improved insights on the functioning and regulation of an intra
islet endothelial microvascular environment.
PMID- 29953915
TI - Insulin as a hormone regulator of the synthesis and release of leptin by white
adipose tissue.
AB - Leptin and its receptor are widely distributed in several tissues, mainly in
white adipose tissue. The serum leptin is highly correlated with body mass index
in rodents and humans, being documented that leptin levels reduces in the fasting
state and increase during refeeding, similarly to insulin release by pancreatic
islets. Insulin appears to increase leptin mRNA and protein expression and its
release by adipocytes. Some studies have suggested that insulin acts through the
activation of the transcription factors: sterol regulatory element binding
protein 1 (SREBP1), CCAAT enhancer binding protein-alpha (C/EBP-alpha) and
specificity protein 1 (Sp1). Insulin stimulates the release of preformed and
newly synthesized leptin by adipocytes through its signaling cascade. Its effects
are blocked by inhibitors of the insulin signaling pathway, as well as by
inhibitors of protein synthesis and agents that increase the intracellular cAMP.
The literature data suggest that chronic hyperinsulinemia increases serum leptin
levels in humans and rodents. In this review, we summarized the most updated
knowledge on the effects of insulin on serum leptin levels, presenting the cell
mechanisms that control leptin synthesis and release by the white adipose tissue.
PMID- 29953916
TI - Comprehensive evaluation of the host responses to infection with differentially
virulent classical swine fever virus strains in pigs.
AB - Classical swine fever virus (CSFV) infection causes most variable clinical
syndromes from chronic or latent infection to acute death, and it is generally
acknowledged that the course of disease is affected by both virus and host
factors. To compare host immune responses to differentially virulent CSFV strains
in pigs, fifteen 8-week-old specific-pathogen-free pigs were randomly divided
into four groups and inoculated with the CSFV Shimen strain (a highly virulent
strain), the HLJZZ2014 strain (a moderately virulent strains), C-strain (an
avirulent strain), and DMEM (mock control), respectively. Infection with the
Shimen or HLJZZ2014 strain resulted in fever, clinical signs and
histopathological lesions, which were not observed in the C-strain-inoculated
pigs, though low viral genome copies were detected in the peripheral blood and
tissue samples. The data showed that the virulence of the strains affected the
outcome of duration and intensity of the disease rather than the tissue tropism
of the virus. Furthermore, leukopenia, lymphocytopenia, differentiation of T
cells, and the secretion of cytokines associated with inflammation or apoptosis
such as interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha),
interleukin 2 (IL-2), IL-4, IL-6, and IL-10 were induced by the virulent CSFV
infection, the differences reflected in onset and extent of the regulation. Taken
together, our results revealed that the major differences among the three strains
resided in the kinetics of host response to the infection: severe and immediate
with the highly virulent strain, while progressive and delayed with the
moderately virulent one. This comparative study will help to dissect the
pathogenesis of CSFV.
PMID- 29953917
TI - Peroxidasin is a novel target of the redox-sensitive transcription factor Nrf2.
AB - Peroxidasin (PXDN) facilitates peroxidative reactions via utilisation of hydrogen
peroxide (H2O2) and has been shown to crosslink collagen IV through sulfilimine
bond formation in the presence of hypohalous acids. Aberrant PXDN expression has
been associated with kidney fibrosis, cancer, congenital eye defects and various
cardiovascular disorders. Since PXDN expression is modified by H2O2, we
hypothesized that a major antioxidant response transcription factor, nuclear
factor erythroid 2-related factor 2 (Nrf2), may regulate PXDN expression. PXDN
expression in response to H2O2 and the Nrf2-specific inducers, tert
butylhydroquinone (tBHQ) and sulforaphane (SFN), was determined by western
blotting and immunofluorescence microscopy, in HeLa and HEK293 cells. Chromatin
immunoprecipitation and luciferase reporter assays were used to investigate the
regulation of PXDN by Nrf2. We observed elevated Nrf2 nuclear translocation and
increased PXDN protein expression in response to H2O2, tBHQ and SFN, in both cell
lines. We found that Nrf2 binds to and increases luciferase reporter gene
expression from the PXDN promoter via a putative Nrf2-binding site. In summary,
we show that PXDN is a novel target of the redox sensitive transcription factor
Nrf2. This finding further highlights the role of PXDN in redox-related processes
and compliments the currently understood pathophysiological functions of PXDN.
PMID- 29953918
TI - Identification of three novel loci of ALDH2 Gene for Serum Folate levels in a
Male Chinese Population by Genome-Wide Association Study.
AB - BACKGROUND: Serum folate is important in clinical researches and DNA synthesis
and methylation. Some loci and genes that are associated with folate levels had
been detected by genome-wide association studies (GWAS), such as rs1801133 in
MTHFR and rs1979277 in SHMT1. Nevertheless, only a small part of variants has
been clearly identified for serum folate. Hence, we conducted a GWAS to discover
new inherited susceptibility and gene-environment interactions on serum folate
concentration. MATERIALS AND METHODS: In a healthy Chinese population of 1999
men, genotyping was performed using Illumina HumanOmni1-Quad BeadChip. Serum
folate levels were measured by enzyme-linked immunosorbent assay (ELISA), pathway
enrichment analysis and statistical analysis were performed by Database for
Annotation, Visualization and Integrated Discovery (DAVID) and Statistic Package
for Social Science (SPSS). RESULTS: We validated that rs1801133 in MTHFR was
significantly involved in serum folate (P = 4.21 * 10-19). Surprisingly, we
discovered three novel loci rs3782886, rs671, and rs4646776 of ALDH2 gene were
suggestively significantly associated with folate serum folate levels in the male
population studied (P = 2.17 * 10-7, P = 3.60 * 10-7, P = 3.99 * 10-7,
respectively) after adjusting for population stratification, BMI and age. Men
with the AA genotype had significantly higher serum folate levels compared with
men with the GG/AG genotype. But we found ALDH2 gene mutation no relation to part
of environmental factors on serum folate levels. CONCLUSION: In a male Chinese
population, genome-wide association study discovered that three novel SNPs
rs3782886, rs671 and rs4646776 of ALDH2 gene were suggestively significantly
associated with serum folate levels.
PMID- 29953919
TI - Ribosomal protein L10A and signaling pathway.
AB - Ribosome: machinery in control of messenger RNA's (mRNAs) and several ribosomal
proteins are in the small and large subunit of the ribosome. Various aspects of
ribosomal proteins have related to cell growth, cell cycle, and diseases.
Ribosomal protein L10A (RpL10A) in shrimp and fruit fly has been demonstrated to
play a role in oogenesis. Interestingly, deletion RpL10A gene (RpL10Ab-/-) germ
line clone of the fruit fly showed a loss of follicle cells surrounding the egg
chamber, but nurse cells appeared normal. This phenotype is reminiscent of
insulin receptor mutants (InR-/-). In contrast, over-expression of RpL10A in the
eyes of the fruit flies resulted in abnormal ommatidia with a loss of red pigment
in the center of the eyes. In this study, the abnormal rearrangements of nuclei
and lack of cell membranes in those eyes were demonstrated. Furthermore, the
expression of InR gene and the InR protein were extensively increased as
determined by real-time PCR and immunohistochemistry, respectively. In addition,
some insulin signaling mediators were also detected. The Akt and FOXO proteins
were highly phosphorylated in the RpL10A over-expressed mutant. The results
revealed that RpL10A induced over-expression of the insulin receptor and
consequently activated in insulin signaling pathway which affects cell
proliferation and we suggest RpL10A stimulates cell proliferation via the insulin
signaling pathway.
PMID- 29953921
TI - Organelle dynamics and viral infections: at cross roads.
AB - Viruses are obligate intracellular parasites of the host cells. A commonly
accepted view is the requirement of internal membranous structures for various
aspects of viral life cycle. Organelles enable favourable intracellular
environment for several viruses. However, studies reporting organelle dynamics
upon viral infections are scant. In this review, we aim to summarize and
highlight modulations caused to various organelles upon viral infection or
expression of its proteins.
PMID- 29953920
TI - Evidence for positive selection on recent human transposable element insertions.
AB - Insertional activity of transposable elements (TEs) has had a major impact on the
human genome; approximately one-half to two-thirds of the genome sequence is
likely to be derived from TE insertions. Several families of human TEs -
primarily Alu, L1 and SVA - continue to actively transpose, thereby generating
insertional polymorphisms among individual genomes. The impact that TE insertions
have on their human hosts' fitness, and accordingly the role that natural
selection plays in shaping patterns of TE polymorphisms among populations, have
yet to be systematically evaluated using whole genome sequence data. We present
here a population genomic study of the effects of natural selection on human
genetic variation that results from the recent activity of TEs. We developed a
genome-wide scan for selection on human TE polymorphisms and applied it to a
dataset of 14,384 locus-specific TE insertions characterized for 1511 individuals
from 15 populations. Our TE selection scan looks for anomalously high population
specific TE insertion allele frequencies that are consistent with the action of
positive (adaptive) selection. To control for the effects of demographic history,
we compared the observed patterns of population-specific TE insertion allele
frequencies to a neutral evolutionary model generated using time forward
simulation of TE insertion allele frequencies among human population groups. This
approach uncovered seven cases of polymorphic TE insertions that appear to have
increased in frequency within specific human populations owing to the effects of
positive selection. Five of the seven putatively selected TE insertions map to
tissue-specific enhancers, and two cases correspond to expression quantitative
trait loci that are associated with inter-individual gene regulatory differences.
This study represents the first report of recent, local adaptation acting on
polymorphic human TEs.
PMID- 29953922
TI - How the phagocyte NADPH oxidase regulates innate immunity.
AB - The phagocyte NADPH oxidase is a multi subunit protein complex that generates
reactive oxygen species at cell membranes and within phagosomes. It is essential
for host defence as evidenced by the severe immunodeficiency syndrome caused by a
loss of one of the subunits. This is known as chronic granulomatous disease
(CGD). However, the phagocyte NADPH oxidase also has a key role to play in
regulating immunity and it is notable that chronic granulomatous disease is also
characterised by autoimmune and autoinflammatory manifestations. This is because
reactive oxygen species play a role in regulating signalling through their
ability to post-translationally modify amino acid residues such as cysteine and
methionine. In this review, I will outline the major aspects of innate immunity
that are regulated by the phagocyte NADPH oxidase, including control of
transcription, autophagy, the inflammasome and type 1 interferon signalling.
PMID- 29953923
TI - The soluble form of LOTUS inhibits Nogo receptor type 1-mediated signaling
induced by B lymphocyte stimulator and chondroitin sulfate proteoglycans.
AB - There are global efforts in developing therapeutic strategies for central nervous
system (CNS) injuries using multimodal approaches. Nogo receptor type 1 (NgR1)
has been known as a primary molecule limiting neuronal regeneration in the adult
CNS. We identified lateral olfactory tract usher substance (LOTUS) as an
endogenous NgR1 antagonist. Membrane-bound LOTUS interacts with NgR1 and inhibits
its function by blocking its ligand binding. Five molecules including Nogo,
myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp),
B lymphocyte stimulator (BLyS) and chondroitin sulfate proteoglycans (CSPGs) have
been identified as NgR1 ligands. These ligands bind to NgR1 and activate NgR1
signaling, leading to axon growth inhibition such as growth cone collapse and
neurite outgrowth inhibition. We have recently reported that the soluble form of
LOTUS (s-LOTUS) also suppressed NgR1-mediated signaling induced by myelin axonal
inhibitors (MAIs) including Nogo, MAG and OMgp by binding with both NgR1 and its
co-receptor p75 neurotrophin receptor (p75NTR). Though s-LOTUS has been reported
to suppress MAIs, whether s-LOTUS also suppresses NgR1 signaling induced by BLyS
and CSPGs remains to be elucidated. Here, we show that s-LOTUS inhibits NgR1
mediated signaling induced by BLyS and CSPGs. Although treatment with s-LOTUS did
not suppress BLyS-NgR1 interaction, s-LOTUS inhibited growth cone collapse and
neurite outgrowth inhibition induced by BLyS and CSPGs in chick dorsal root
ganglion (DRG) neurons. Furthermore, s-LOTUS compensated for the suppressive
function of endogenous LOTUS in NgR1-mediated signaling in olfactory bulb neurons
of lotus-knockout mice. These findings suggest that s-LOTUS is a potent
therapeutic agent for neuronal regeneration in the CNS injuries.
PMID- 29953924
TI - Lack of association between MTHFR C677T Gene polymorphism with alcohol
dependence: A meta-analysis of case-control studies.
AB - Many studies have reported that MTHFR C677T (rs 1801133) polymorphism is
associated with the risk of alcohol dependence(AD). However, there are
conflicting results regarding this relationship. In this article, we performed a
meta-analysis of case-control studies to assess synthetically the influence of
MTHFR C677T polymorphism on the risk of AD. All relevant studies were searched
from Cochrane Library, EmBase, PubMed, and Web of science. 7 studies were
included to evaluate the strength of associations between the MTHFR C677T
polymorphism and AD by pooled odds ratios (ORs) and 95% confidence intervals
(CIs). The present meta-analysis evaluated a total of 1066 AD patients and 1049
controls and showed that MTHFR C677T polymorphism was not significantly
associated with AD susceptibility in all five genetic models (Allelic, T vs C: OR
= 1.04,95% CI: 0.83-1.31, P = 0.73; Homozygous, TT vs CC: OR = 0.98,95% CI: 0.57
1.68, P = 0.94; Heterozygous, TT vs CT: OR = 0.87,95% CI: 0.64-1.19, P = 0.39;
Dominant, TT + CT vs CC: OR = 1.12,95% CI: 0.92-1.35, P = 0.26; Recessive, TT vs
CT + CC: OR = 0.93,95% CI: 0.58-1.47, P = 0.74). On subgroup analysis by
ethnicity, there was still insignificant association was detected in the
Caucasians and Asians under the five genetic models respectively. In conclusion,
the present data revealed that MTHFR C677T polymorphism may not be associated
with AD susceptibility. Further well designed studies in a larger population and
biological functional analysis of MTHFR are needed to elucidate the role of MTHFR
C677T Gene polymorphism in AD.
PMID- 29953925
TI - Disrupted amplitude of low-frequency fluctuations and causal connectivity in
Parkinson's disease with apathy.
AB - Apathy is a common non-motor symptom in Parkinson's disease (PD). We aimed to
explore its associated neural substrates changes via amplitude of low-frequency
fluctuations (ALFF) and granger causality analysis (GCA). Resting-state
functional magnetic resonance imaging (rs-fMRI) scans were performed in 20 PD
patients with apathy (PD-A), 22 PD patients without apathy (PD-NA) and 19 healthy
volunteers. GCA, a new method exploring direction from one brain region to
another, was based on brain regions showing alterations of neural activity as
seeds, which were examined utilizing ALFF approach. The relationships between
ALFF or GCA and apathetic symptoms were also assessed. Relative to PD-NA group,
PD-A group indicated decreased ALFF in left orbital middle frontal gyrus and
bilateral superior frontal gyrus (SFG). Only ALFF values in right SFG were
negatively correlated with Apathy Scale (AS) scores. Then GCA with the seed of
right SFG showed a positive feedback from right thalamus to ipsilateral SFG,
which was positively correlated with AS scores. In conclusion, dysfunction in SFG
and a positive feedback from thalamus to ipsilateral SFG contributed to presence
of PD-related apathy, providing a new perspective for future studies on apathy in
PD.
PMID- 29953926
TI - Monoamine oxidase-dependent histamine catabolism accounts for post-ischemic
cardiac redox imbalance and injury.
AB - Monoamine oxidase (MAO), a mitochondrial enzyme that oxidizes biogenic amines
generating hydrogen peroxide, is a major source of oxidative stress in cardiac
injury. However, the molecular mechanisms underlying its overactivation in
pathological conditions are still poorly characterized. Here, we investigated
whether the enhanced MAO-dependent hydrogen peroxide production can be due to
increased substrate availability using a metabolomic profiling method. We
identified N1-methylhistamine -the main catabolite of histamine- as an important
substrate fueling MAO in Langendorff mouse hearts, directly perfused with a
buffer containing hydrogen peroxide or subjected to ischemia/reperfusion
protocol. Indeed, when these hearts were pretreated with the MAO inhibitor
pargyline we observed N1-methylhistamine accumulation along with reduced
oxidative stress. Next, we showed that synaptic terminals are the major source of
N1-methylhistamine. Indeed, in vivo sympathectomy caused a decrease of N1
methylhistamine levels, which was associated with a marked protection in post
ischemic reperfused hearts. As far as the mechanism is concerned, we demonstrate
that exogenous histamine is transported into isolated cardiomyocytes and triggers
a rise in the levels of reactive oxygen species (ROS). Once again, pargyline
pretreatment induced intracellular accumulation of N1-methylhistamine along with
decrease in ROS levels. These findings uncover a receptor-independent mechanism
for histamine in cardiomyocytes. In summary, our study reveals a novel and
important pathophysiological causative link between MAO activation and histamine
availability during pathophysiological conditions such as oxidative
stress/cardiac injury.
PMID- 29953927
TI - Formulation of delivery systems with risperidone based on biodegradable
terpolymers.
AB - Risperidone is applied in oral dosage formulations in the treatment of mental
diseases. Current trends point toward parenteral delivery systems based on
poly(lactide-co-glycolide), with wafers or rods being the more attractive option
than the routinely used intramuscular suspension with microparticles. The aim of
our work was to study the utility of solution casting and hot melt extrusion in
the formulation of wafers and rods with risperidone based on terpolymers, namely
poly(lactide-co-glycolide-co-trimethylene carbonate) and poly(lactide-co
glycolide-co-epsilon-caprolactone). Synthesis of the terpolymers was carried out
by using a non-toxic zirconium initiator and a racemic (LL/DD) or optically
active form of the lactide monomer. The delivery systems were analyzed by NMR,
DSC, GPC, and SEM. The release profile was monitored by HPLC. Terpolymer chain
microstructure, glass transition temperature, and morphology revealed unchanged
values after formulation. Solution casting resulted in a drop in molecular weight
to a smaller degree than hot melt extrusion. The presence of risperidone
influenced another decrease in molecular weight. Both methods are adequate for
the formulation of delivery systems based on terpolymers for prolonged release of
risperidone. An adequate selection of monomer composition in terpolymers allows
to control the release period. Risperidone was released in three phases, however,
the burst effect was observed for poly(L-lactide-co-glycolide-co-epsilon
caprolactone).
PMID- 29953928
TI - A practical framework for implementing Quality by Design to the development of
topical drug products: Nanosystem-based dosage forms.
AB - Skin has been increasingly recognized as an important drug administration route
with topical formulations, offering a targeted approach for the treatment of
several dermatological disorders. The effectiveness of this route is hampered by
its natural barrier, the stratum corneum (SC), and hence, different strategies
have been investigated to improve percutaneous drug transport. The design of
nanodelivery systems, aiming at solving skin delivery issues, have been largely
explored, due to their potential to revolutionize dermal therapies, improving
therapeutic effectiveness and reducing side effects. Apart from nanosystem
benefits, the fulfilment of the reproducibility requirements and quality
standards still limit their industrial production. The optimization of nanosystem
formulation and manufacturing process is complex, usually involving a large
number of variables. Therefore, a science- and risk-oriented approach, such as
Quality by Design (QbD) will provide a comprehensive and noteworthy knowledge,
yielding high quality drug products without extensive regulatory burden. This
review aims to set up the basis for QbD development approach, encompassing
preliminary and systematic risk assessments, with critical process parameters
(CPPs) and critical material attributes (CMAs) identification, of different
nanosystems potentially used in dermal therapies.
PMID- 29953929
TI - Sex-dependent co-occurrence of hypoxia and beta-amyloid plaques in hippocampus
and entorhinal cortex is reversed by long-term treatment with ubiquinol and
ascorbic acid in the 3 * Tg-AD mouse model of Alzheimer's disease.
AB - Structural and functional abnormalities in the cerebral microvasculature have
been observed in Alzheimer's disease (AD) patients and animal models. One cause
of hypoperfusion is the thickening of the cerebrovascular basement membrane
(CVBM) due to increased collagen-IV deposition around capillaries. This study
investigated whether these and other alterations in the cerebrovascular system
associated with AD can be prevented by long-term dietary supplementation with the
antioxidant ubiquinol (Ub) stabilized with Kaneka QH P30 powder containing
ascorbic acid (ASC) in a mouse model of advanced AD (3 * Tg-AD mice, 12 months
old). Animals were treated from prodromal stages of disease (3 months of age)
with standard chow without or with Ub + ASC or ASC-containing vehicle and
compared to wild-type (WT) mice. The number of beta-amyloid (Abeta) plaques in
the hippocampus and entorhinal cortex was higher in female than in male 3 * Tg-AD
mice. Extensive regions of hypoxia were characterized by a higher plaque burden
in females only. This was abolished by Ub + ASC and, to a lesser extent, by ASC
treatment. Irrespective of Abeta burden, increased collagen-IV deposition in the
CVBM was observed in both male and female 3 * Tg-AD mice relative to WT animals;
this was also abrogated in Ub + ASC- and ASC-treated mice. The chronic
inflammation in the hippocampus and oxidative stress in peripheral leukocytes of
3 * Tg-AD mice were likewise reversed by antioxidant treatment. These results
provide strong evidence that long-term antioxidant treatment can mitigate plasma
oxidative stress, amyloid burden, and hypoxia in the AD brain parenchyma.
PMID- 29953930
TI - Determination of mercury in hair of children.
AB - Although high or repeated exposure to different forms of Hg can have serious
health consequences, the most important toxicity risk for humans is as
methylmercury (MeHg) which exposure is mainly through consumption of fish.
Generally, more than the 80% of Hg in hair is as MeHg, which is taken up by hair
follicles as MeHg-cysteine complexes. In this context, hair samples were
collected from 200 children (7 years) living in a coastal site in the North-East
(A) of Italy and from 299 children (6-11 years) living in a urban area of South
of Italy (B) to determine the levels of MeHg. Considering the neurotoxicity of
MeHg, children were subjected to cognitive and neuropsychological tests. The hair
values of Hg in the children population groups were comparable with data reported
in other international surveys. On the other hand, combining results of the
neurological tests with Hg levels, a possible relationship between Hg and an
increase of the errors average reported in some neurological tests has been
noted. Although the Hg levels were not elevated, a possible neurological
influence in children, a population more susceptible than adults, might not be
excluded, but the influence on neurological performances of the children could be
also due to the family environment (socio economic status, educational level,
etc.).
PMID- 29953931
TI - RhoA regulates Drp1 mediated mitochondrial fission through ROCK to protect
cardiomyocytes.
AB - Cardiac ischemia/reperfusion, loss of blood flow and its subsequent restoration,
causes damage to the heart. Oxidative stress from ischemia/reperfusion leads to
dysfunction and death of cardiomyocytes, increasing the risk of progression to
heart failure. Alterations in mitochondrial dynamics, in particular mitochondrial
fission, have been suggested to play a role in cardioprotection from oxidative
stress. We tested the hypothesis that activation of RhoA regulates mitochondrial
fission in cardiomyocytes. Our studies show that expression of constitutively
active RhoA in cardiomyocytes increases phosphorylation of Dynamin-related
protein 1 (Drp1) at serine-616, and leads to localization of Drp1 at
mitochondria. Both responses are blocked by inhibition of Rho-associated Protein
Kinase (ROCK). Endogenous RhoA activation by the GPCR agonist sphingosine-1
phosphate (S1P) also increases Drp1 phosphorylation and its mitochondrial
translocation in a RhoA and ROCK dependent manner. Consistent with the role of
mitochondrial Drp1 in fission, RhoA activation in cardiomyocytes leads to
formation of smaller mitochondria and this is attenuated by inhibition of ROCK,
by siRNA knockdown of Drp1 or by expression of a phosphorylation-deficient Drp1
S616A mutant. In addition, activation of RhoA prevents cell death in
cardiomyocytes challenged by oxidative stress and this protection is blocked by
siRNA knockdown of Drp1 or by Drp1 S616A expression. Taken together our findings
demonstrate that RhoA activation can regulate Drp1 to induce mitochondrial
fission and subsequent cellular protection, implicating regulation of fission as
a novel mechanism contributing to RhoA-mediated cardioprotection.
PMID- 29953932
TI - A histogram analysis of diffusion and perfusion features of cervical cancer based
on intravoxel incoherent motion magnetic resonance imaging.
AB - OBJECTIVE: To evaluate the diagnostic potential based on histogram analysis of
IVIM parameters between uterine cervical cancers (CC) - normal myometrium (Myo)
versus CC - gluteus maximus muscle (GM) and to study the feasibility of histogram
analysis of IVIM parameters to differentiate the early from locally advanced
stage CCs. METHODS: 64 patients with pathologically confirmed CC were enrolled.
Histogram indices mean, median, 25th, and d 75th percentile of apparent diffusion
coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient
(D*), and perfusion fraction (f) value of entire tumor were statistically
analyzed and compared between CC - GM versus CC - Myo, as well as between early
and locally advanced stage CCs. A multivariate analysis was performed to identify
indices that could best distinguish early from locally advanced stage CC.
Receiver operating characteristic curves (ROC) were used to evaluate the
diagnostic efficiency of every histogram parameter. RESULTS: All the tested
histogram indices significantly differed between the patients with CC - GM vs. CC
- Myo, nonetheless, CC - GM yielded higher range area under the curve (AUC) value
of 0.8-0.99 vs. 0.6-0.99. The additional significant difference was found among
all the tested histogram indices of D*, mean, median, and 75th percentile of f,
mean and 75th percentile of ADC, and 75th percentile of D discriminating early
from locally advanced CCs. ROC curves indicated that the 75th percentile of D*
value 28.17 * 10-3 mm2/s could best differentiate early from locally advanced
stage CCs, with AUC of 0.776. In the multivariate analysis, ROC indicated the
50th percentile of D* and f was the most significant with AUCs of 0.856.
CONCLUSIONS: The histogram analysis of IVIM parameters depicted that gluteus
maximus served better reference tissue in comparison to myometrium. The histogram
index 75th percentile of ADC, D, D*, and f may serve a diagnostic biomarker to
differentiate the early from locally advanced stage CCs.
PMID- 29953933
TI - Neuroimaging markers of antipsychotic treatment response in schizophrenia: An
overview of magnetic resonance imaging studies.
AB - Antipsychotic drugs are the primary treatment for psychosis, yet individual
response to their administration remains variable. At present, no biological
predictors of response exist to guide clinicians as they select treatments for
patients, and our understanding of the neurobiology underlying the heterogeneity
of outcomes remains limited. Magnetic Resonance Imaging (MRI) has been applied by
numerous studies to examine the response to antipsychotic treatment, though a
large gap remains between their results and our clinical practice. To advance
patient care with precision medicine approaches, prior work must be accounted for
and built upon with future studies. This review provides an overview of studies
that relate treatment outcome to various MRI-related measures, including
structural, spectroscopic, diffusion tensor, and functional imaging. Knowledge
derived from these studies will be discussed along with future directions for the
field.
PMID- 29953934
TI - Effectiveness of the prefrontal repetitive transcranial magnetic stimulation on
cognitive profiles in depression, schizophrenia, and Alzheimer's disease: A
systematic review.
AB - Repetitive transcranial magnetic stimulation (rTMS) is an effective clinical
intervention for various neuropsychiatric diseases. However, it is still unclear
whether rTMS has an effect on cognitive functioning. In this review, we aimed to
systematically evaluate the cognitive effects of rTMS in depression,
schizophrenia, and Alzheimer's disease. We searched PubMed (1996-2018) under the
set terms to review randomized controlled trials (RCT) to examine the
effectiveness of rTMS administered to the dorsolateral prefrontal cortex (DLPFC)
and evaluated cognitive functions in patients with depression, schizophrenia, and
Alzheimer's disease. Two authors reviewed each article and came to consensus on
the inclusion and exclusion criteria. All eligible studies were reviewed,
duplicates were removed, and data were extracted individually. The search
identified 579 articles, 31 of which met inclusion and exclusion criteria. Among
them, 15 were conducted in patients with depression, 11 in patients with
schizophrenia, and 5 in patients with Alzheimer's disease. Specifically, 6
studies demonstrated a significant improvement of executive function across these
diseases. Further, no evidence for cognitive adverse effects was found in these
included rTMS studies. Although the heterogeneity between studies in terms of
cognitive measures applied, stimulation parameters, and participants limits the
ability to generalize conclusions, this review demonstrated that prefrontal rTMS
could exert pro-cognitive effects on executive function and attention in some
patients with depression but inconsistent cognitive impacts in any of the
examined domains especially in patients with schizophrenia and Alzheimer's
disease. The results warrant further rTMS studies that include systematic
assessment of cognition across various neuropsychiatric diseases.
PMID- 29953935
TI - Methamphetamine-associated difficulties in cognitive control allocation may
normalize after prolonged abstinence.
AB - Chronic heavy methamphetamine use likely causes dopaminergic neurotoxicity, which
is commonly thought to result in cognitive control deficits. Both of these
alterations may persist even after the use is discontinued, but tend to (partly)
improve with increasing duration of abstinence. While several studies have
demonstrated that the reinstatement of comparatively normal dopaminergic
signaling may take months, if not years, the amelioration of cognitive deficits
has predominantly been investigated in much shorter intervals of several weeks to
less than half a year. Against this background, we set out to investigate the
effects on prolonged abstinence in n = 27 abstinent former methamphetamine users
in a cross-sectional design using behavioral and neurophysiological measures of
cognitive control. Our behavioral results suggest that former users struggled to
identify and adapt to different degrees of cognitive control requirements, which
made their behavioral performance less expedient than that of healthy controls.
On the neurophysiological level, this was reflected by reduced modulations of the
N2-N450 amplitude in response to high vs. low cognitive control requirements.
Yet, those effects could only be observed in methamphetamine users who had been
abstinent for a relatively short time (mean 9.9; max. 18 months), but not in
former users who had been abstinent two years or longer. While this finding alone
does not allow for causal inferences, it suggests that the amelioration of
control deficits may take longer than what is commonly investigated (1-6 months).
Hence, some of the statements about permanent/irreversible dopamine-dependent
executive dysfunctions in former methamphetamine users should be interpreted with
caution.
PMID- 29953936
TI - Alterations in resting-state functional connectivity in substance use disorders
and treatment implications.
AB - Substance use disorders (SUD) are diseases of the brain, characterized by
aberrant functioning in the neural circuitry of the brain. Resting state
functional connectivity (rsFC) can illuminate these functional changes by
measuring the temporal coherence of low-frequency fluctuations of the blood
oxygenation level-dependent magnetic resonance imaging signal in contiguous or
non-contiguous regions of the brain. Because this data is easy to obtain and
analyze, and therefore fairly inexpensive, it holds promise for defining
biological treatment targets in SUD, which could help maximize the efficacy of
existing clinical interventions and develop new ones. In an effort to identify
the most likely "treatment targets" obtainable with rsFC we summarize existing
research in SUD focused on 1) the relationships between rsFC and functionality
within important psychological domains which are believed to underlie relapse
vulnerability 2) changes in rsFC from satiety to deprived or abstinent states 3)
baseline rsFC correlates of treatment outcome and 4) changes in rsFC induced by
treatment interventions which improve clinical outcomes and reduce relapse risk.
Converging evidence indicates that likely "treatment target" candidates, emerging
consistently in all four sections, are reduced connectivity within executive
control network (ECN) and between ECN and salience network (SN). Other potential
treatment targets also show promise, but the literature is sparse and more
research is needed. Future research directions include data-driven prediction
analyses and rsFC analyses with longitudinal datasets that incorporate time since
last use into analysis to account for drug withdrawal. Once the most reliable
biological markers are identified, they can be used for treatment matching,
during preliminary testing of new pharmacological compounds to establish clinical
potential ("target engagement") prior to carrying out costly clinical trials, and
for generating hypotheses for medication repurposing.
PMID- 29953937
TI - Cryptic biodiversity in the freshwater fishes of the Kimberley endemism hotspot,
northwestern Australia.
AB - The prevalence of unrecognised cryptic species impairs biodiversity estimates,
clouds biological research and hinders conservation planning. As the rate of
cryptic species detection increases globally, research is needed to determine how
frequent cryptic species are, whether they are more common in given management
regions, and whether these patterns are consistent across taxonomic groups. The
Kimberley region in remote northwestern Australia harbours some of the most
speciose, and morphologically and functionally diverse, endemic animal and plant
communities on the continent. The rugged and changeable landscape also appears to
contain a large proportion of cryptic terrestrial species, raising the question
of whether similar patterns are also found among aquatic taxa, which have yet to
be studied using integrative systematic approaches. If true, then the actual
levels of aquatic biodiversity are yet to be fully realised. Here we conducted a
molecular assessment of where species boundaries may exist in the Kimberley
regions' most speciose freshwater fish family, the Terapontidae (grunters), with
a combined morphological assessment of the regions' most speciose terapontid
genus, Syncomistes. Assessment of nuclear markers (54 allozyme loci), sequence
data (mitochondrial cytochrome b (cytb); nuclear recombination activation gene
one (RAG1)) and 31 meristic and 36 morphometric characters provides evidence for
13 new candidate species across three different genera. Many of these candidate
species are narrow range endemics. Our findings raise several questions about the
evolutionary origin of the Kimberley's endemic fish fauna and highlight the
likelihood that freshwater fish species diversity in the Kimberley is severely
under-represented by current systematic frameworks, with significant implications
for ecological research, conservation and management.
PMID- 29953938
TI - How is structural divergence related to evolutionary information?
AB - The analysis of evolutionary information in a protein family, such as
conservation and covariation, is often linked to its structural information.
Multiple sequence alignments of distant homologous sequences are used to measure
evolutionary variables. Although high structural differences between proteins can
be expected in such divergent alignments, most works linking evolutionary and
structural information use a single structure ignoring the structural variability
within protein families. The goal of this work is to elucidate the relevance of
structural divergence when sequence-based measures are integrated with structural
information. We found that inter-residue contacts and solvent accessibility
undergo large variations in protein families. Our results show that high
covariation scores tend to reveal residue contacts that are conserved in the
family, instead of protein or conformer specific contacts. We also found that
residue accessible surface area shows a high variability between structures of
the same family. As a consequence, the mean relative solvent accessibility of
multiple structures correlates better with the conservation pattern than the
relative solvent accessibility of a single structure. We conclude that the use of
comprehensive structural information allows a more accurate interpretation of the
information computed from sequence alignments. Therefore, considering structural
divergence would lead to a better understanding of protein function, dynamics,
and evolution.
PMID- 29953939
TI - Efficient, Efficacious, Effective: Still a Long Way to Go for Diuretic Treatment
of Acute Decompensated Heart Failure.
PMID- 29953940
TI - Establishing Goals of Care for Patients With Stroke and Feeding Problems: An
Interdisciplinary Trigger-Based Continuous Quality Improvement Project.
AB - BACKGROUND: Few patients with dysphagia because of stroke receive early
palliative care (PC) to align treatment goals with their values, as called for by
practice guidelines, particularly before enteral access procedures for artificial
nutrition. MEASURES: To increase documented goals of care (GOC) discussions among
acute stroke patients before feeding gastrostomy tube placement. INTERVENTION: We
undertook a rapid-cycle continuous quality improvement process with
interdisciplinary planning, implementation, and performance review to
operationalize an upstream trigger for PC referral prompted by the speech and
language pathology evaluation. OUTCOMES: During a six-month period, 21 patients
underwent gastrostomy tube placement; 52% had preprocedure GOC discussions
postintervention, with the rate of compliance increasing steadily from 13%
(11/87, preintervention) to 100% (2/2) in the final two months.
CONCLUSIONS/LESSONS LEARNED: We effectively increased documented GOC discussions
before feeding gastrostomy tube placement among stroke patients. Systems-based
tools and education will enhance this upstream trigger model to ensure early PC
for stroke patients.
PMID- 29953941
TI - Reframing Global Palliative Care Advocacy for the Sustainable Development Goal
Era: A Qualitative Study of the Views of International Palliative Care Experts.
AB - CONTEXT: The World Health Assembly Palliative Care Resolution in 2014 and the
inclusion of palliative care within the sustainable development goals raised
optimism that palliative care would no longer be a peripheral aspect of global
health. However, no funding, accountability measures, or indicators for
palliative care development accompanied these policy developments. This risks
health actors continuing to prioritize the attainment of better known target
driven aspects of health care. OBJECTIVES: To explore the attitudes of
international palliative care experts regarding how the future development of
palliative care can be accelerated. METHODS: About 16 international palliative
care experts were interviewed for their epistemic expertise. Participants were
interviewed face to face or via Skype. Interviews were recorded, transcribed
nonverbatim, and analyzed using a thematic approach (NVivo). RESULTS:
Participants strongly supported the rollout of national palliative care policies
around the world for two reasons: to ensure palliative care attracts national
funding streams and to attract global funding for palliative care. The absence of
a global indicator for palliative care development was considered a severe
impediment to the inclusion of palliative care within global efforts toward
universal health care. Advocacy partnerships, using human rights approaches with
economic frames, were considered the most effective methods of influencing
policymakers. CONCLUSION: Palliative care represents a value proposition that is
not currently being maximized by advocacy. Advocates should consider palliative
care developmentally, focusing on key asks for development and consider how
palliative care can contribute to other international development priorities, in
particular poverty reduction.
PMID- 29953942
TI - An examination of the association between prenatal cocaine exposure and brain
activation measures of arousal and attention in young adults: An fMRI study using
the Attention Network Task.
AB - Prenatal drug exposure, including cocaine, alcohol, marijuana, and tobacco, is
associated with deficits in behavioral regulation and attention. Using fMRI, the
objective of this study was to characterize the association between prenatal
cocaine exposure (PCE) and the underlying neural substrates associated with
behavioral outcomes of attention. Forty-seven young adults were recruited for
this study from the ongoing Maternal Health Practices and Child Development
(MHPCD) Project, a longitudinal study of the effects of PCE on growth, behavior,
and cognitive function. Three groups were compared: 1) prenatal exposure to
cocaine, alcohol, marijuana, and tobacco (CAMT, n = 15), 2) prenatal exposure to
alcohol, marijuana, and tobacco (AMT, n = 17), and 3) no prenatal exposure to
drugs (Controls, n = 15). Subjects were frequency matched on gender, race,
handedness, and 15-year IQ. This study used the theoretical model proposed by
Posner and Peterson (1990), which posits three dissociable components of
attention: alerting, orienting, and executive attention. Subjects completed a
functional MRI (fMRI) scan while performing the Attention Network Task, a
validated neuroimaging measure of the 3-network model of attention. Behavioral
and fMRI data revealed no associations between PCE and task accuracy, speed of
processing, or activation in key brain regions associated with each of the
attention networks. The results of this study show that any subtle differences in
brain function associated with PCE are not detectable using the ANT task and
fMRI. These results should be interpreted in the context of other studies that
have found associations between PCE and arousal with emotionally arousing
stimuli, compared to this study that found no associations using emotionally
neutral stimuli.
PMID- 29953943
TI - Beyond a neurotransmitter: The role of serotonin in inflammation and immunity.
AB - Serotonin (5-HT), a well-known neurotransmitter in the brain, also plays an
important role in peripheral tissues, including the immune system. There is a
growing body of evidence suggesting that many different types of immune cells
express the machinery to generate, store, respond to and/or transport serotonin,
including T cells, macrophages, mast cells, dendritic cells and platelets. In
addition, there is emerging evidence of a possible connection between T cells,
serotonin and mood disorders. How 5-HT interacts with the peripheral immune
system and if this signaling is associated with behavioral phenotypes found in
mood disorders like major depressive disorder (MDD) is not well understood. In
this review, we summarize the existing literature on what is known about the link
between 5-HT and the immune system and the effects of 5-HT signaling on different
cells of the peripheral immune system, with a particular focus on T cells. In
addition, we review the current evidence that peripheral immune system
alterations and CNS function may be interrelated and the possible implications of
these findings for drug discovery.
PMID- 29953944
TI - Response to: "Drugs for treatment for alcohol use disorders expose to
interactions with others ... for little benefit if any".
PMID- 29953945
TI - Systemic Sclerosis as an Indication for Autologous Hematopoietic Cell
Transplantation: Position Statement from the American Society for Blood and
Marrow Transplantation.
AB - Systemic sclerosis is a progressive inflammatory disease that is frequently fatal
and has limited treatment options. High-dose chemotherapy with autologous
hematopoietic cell transplantation (AHCT) has been evaluated as treatment for
this disease in observational studies, multicenter randomized controlled clinical
trials, and meta-analyses. On behalf of the American Society for Blood and Marrow
Transplantation (ASBMT), a panel of experts in transplantation and rheumatology
was convened to review available evidence and make a recommendation on AHCT as an
indication for systemic sclerosis. Three randomized trials have compared the
efficacy of AHCT with cyclophosphamide only, and all demonstrated benefit for the
AHCT arm for their primary endpoint (improvement in the American Scleroderma Stem
Cell versus Immune Suppression Trial, event-free survival in Autologous Stem Cell
Transplantation International Scleroderma trial, and change in global rank
composite score in Scleroderma: Cyclophosphamide or Transplantation trial). AHCT
recipients also had better overall survival and a lower rate of disease
progression. These findings have been confirmed in subsequent meta-analyses.
Based on this high-quality evidence, the ASBMT recommends systemic sclerosis
should be considered as a "standard of care" indication for AHCT. Close
collaboration between rheumatologists and transplant clinicians is critical for
optimizing patient selection and patient outcomes. Transplant centers in the
United States are strongly encouraged to report patient and outcomes data to the
Center for International Blood and Marrow Transplant Research on their patients
receiving AHCT for this indication.
PMID- 29953946
TI - Potential large scale production of meningococcal vaccines by stable
overexpression of fHbp in the rice seeds.
AB - Factor H binding protein (fHbp) is the most promising vaccine candidate against
serogroup B of Neisseria meningitidis which is a major cause of morbidity and
mortality in children. In order to facilitate large scale production of a
commercial vaccine, we previously used transgenic Arabidopsis thaliana, but plant
derived fHbp is still far away from a commercial vaccine due to less biomass
production. Herein, we presented an alternative route for the production of
recombinant fHbp from the seeds of transgenic rice. The OsrfHbp gene encoding
recombinant fHbp fused protein was introduced into the genome of rice via
Agrobacterium-mediated transformation. The both stable integration and
transcription of the foreign OsrfHbp were confirmed by Southern blotting and RT
PCR analysis respectively. Further, the expression of fHbp protein was measured
by immunoblotting analysis and quantified by ELISA. The results indicated that
fHbp was successfully expressed and the highest yield of fHbp was 0.52 +/- 0.03%
of TSP in the transgenic rice seeds. The purified fHbp protein showed good
antigenicity and immunogenicity in the animal model. The results of this
experiment offer a novel approach for large-scale production of plant-derived
commercial vaccine fHbp.
PMID- 29953947
TI - Neural engagement with online educational videos predicts learning performance
for individual students.
AB - Online educational materials are largely disseminated through videos, and yet
there is little understanding of how these videos engage students and fuel
academic success. We hypothesized that components of the electroencephalogram
(EEG), previously shown to reflect video engagement, would be predictive of
academic performance in the context of educational videos. Two groups of subjects
watched educational videos in either an intentional learning paradigm, in which
they were aware of an upcoming test, or in an incidental learning paradigm, in
which they were unaware that they would be tested. "Neural engagement" was
quantified by the inter-subject correlation (ISC) of the EEG that was evoked by
the videos. In both groups, students with higher neural engagement retained more
information. Neural engagement also discriminated between attentive and
inattentive video viewing. These results suggest that this EEG metric is a marker
of the stimulus-related attentional mechanisms necessary to retain information.
In the future, EEG may be used as a tool to design and assess online educational
content.
PMID- 29953948
TI - Anesthetics alleviate learning and memory impairment induced by electroconvulsive
shock by regulation of NMDA receptor-mediated metaplasticity in depressive rats.
AB - Along with its outstanding antidepressant effect, electroconvulsive shock (ECS)
can induce learning and memory impairment. Propofol and ketamine have shown to be
useful in alleviating the learning and memory impairment. Nevertheless, the
mechanism still remains unclear. This study investigated the role of NMDA
receptor (NMDAR)-mediated metaplasticity in the learning and memory impairment
induced by ECS, as well as the neuroprotective effect of propofol and ketamine in
depressive rats. Rats received ECS or ECS under anesthetics after chronic
unpredictable mild stress procedure. Long-term potentiation (LTP) was tested by
extracellular recording. LTD/LTP threshold was assessed by stimulation of
different frequencies. Additionally, NMDAR-mediated field excitatory postsynaptic
potential (fEPSP) and NMDAR input/output relationship were detected under
hippocampal slice perfusion. Results showed that propofol or low-dose ketamine
could partially alleviate ECS-induced LTP impairment, while propofol combined
with low-dose ketamine almost reversed the LTP impairment. LTP under ECS was
increased by stronger stimulation. ECS could up-regulated LTD/LTP threshold,
while propofol or ketamine could down-regulate it. Moreover, ECS activated NMDAR,
while propofol and ketamine could inhibit the activation of NMDAR. NMDAR
input/output relationship decrease was induced by preconditioning (an analog of
ECS in hippocampal slice), however, NMDAR input/output relationship increased by
propofol or ketamine. In conclusion, ECS-induced cognitive impairment is caused
by NMDAR-mediated metaplasticity via up-regulation of LTD/LTP threshold. Propofol
or ketamine alleviates the cognitive impairment, possibly by down-regulating the
threshold via inhibition of NMDAR activation induced by ECS.
PMID- 29953949
TI - Facultative hypothermia as a survival strategy during snowstorm induced food
shortages in Antarctic storm-petrel chicks.
AB - Wilson's storm-petrels (Oceanites oceanicus) are the smallest marine birds
breeding in Antarctica, where events like snowstorms often prevent parents from
providing food daily for their offspring. To minimize energy expenses, Wilson's
storm-petrel chicks can reduce their metabolism and body temperature by entering
hypothermia. Hypothermia is reported to impact development, hence we hypothesized
that hypothermia will be majorly used after long fasting periods. Chick
development in a breeding colony of Wilson's storm-petrels on the South Shetland
Islands was monitored daily during three consecutive summers by recording chicks'
body mass and temperature, as well as environmental parameters. Provisioning, and
body conditions were highest in 2017, and chicks became hypothermic most
frequently in 2016. Body temperature was influenced by age, mass, body condition,
and minimal nocturnal temperatures. While most chicks were able to maintain
stable body temperatures when not fed for one day, some chicks' body temperatures
decreased by up to 21 degrees C. Age did not differ between those two groups,
but chicks maintaining their active body temperatures had higher body conditions.
Snowstorms were typically followed by several days of unreliable food
provisioning and continuous days of fasting. Most chicks were hypothermic during
this time, and were hence able to survive periods of food shortages, reverse
their low body temperatures after the next feeding event, and regain body mass.
We conclude that hypothermia is a strong survival strategy to endure times of
fasting, which might be necessary for Antarctic storm-petrel chicks to reach
adulthood. However, in future scenarios, which may include more frequent
snowstorms due to climate change, malnourishment could lead to more frequent use
of hypothermia, which could affect chicks' development.
PMID- 29953950
TI - Rate of power development of the knee extensors across the adult life span: A
cross-sectional study in 1387 Flemish Caucasians.
AB - A growing body of research in elderly populations suggests that the early phase
of an explosive muscle contraction (i.e., <=200 ms) may be more functionally
relevant than peak values. However, age-related variation in early phase
explosive strength has never been investigated across the full-adult life span.
This cross-sectional study investigated the age-related changes in the rate of
power development (RPD) and compared it to the changes in peak power (Ppeak),
both in terms of magnitude and onset, across the adult life span. Age-related
declines in power and determinants of muscle power were compared between sexes.
1387 adults (?813, ?574), aged 18-78 years, performed three maximal isoinertial
knee extensor tests at 20% of their isometric maximum on a Biodex dynamometer.
Ppeak was calculated as the highest value and RPD as the linear slope of the
power-time curve. Velocity (v) and torque (T) at Ppeak were registered. In both
men and women, the decline in Ppeak and RPD was already apparent from 40 years
onwards. Annual percent decline rates were greater for RPD (-1.1% for men and
1.3% for women) than Ppeak (-0.9% for men and -1.0% for women). Velocity at Ppeak
showed the lowest annual percent decline rates (-0.3% for men and -0.4% for
women). Men performed better than women on all parameters (all p < 0.001).
Velocity at Ppeak tended to decline more in women than in men (p = 0.065). To
conclude, both knee extensor Ppeak and RPD can be used to screen for age-related
neuromuscular weaknesses at an early age. Both sexes seem equally susceptible to
age-related declines in knee extensor power. In addition to traditional slow
speed resistance exercise, prevention strategies should include explosive
exercises. Explosive exercises may be especially relevant in women, considering
that they tend to decline more in the velocity component of muscle power.
PMID- 29953951
TI - Effect of exercise order of combined aerobic and resistance training on arterial
stiffness in older men.
AB - Arterial stiffness increases with advancing age, and is as an emerging biomarker
in the assessment of vascular health. Some studies suggest that high-intensity
resistance training increases arterial stiffness, but low- to moderate-intensity
resistance training does not effect on arterial stiffening. Current evidence
suggests that performing aerobic exercise after resistance training improved
arterial stiffness in the young men and women. However, few studies have been
conducted on the effects of the order of combined training on arterial stiffness
in the elderly. The purpose of this study was to examine the effects of exercise
order of combined aerobic and resistance training into the same session on body
composition, muscle strength and arterial stiffness in older men. Forty-five
older men (aged 70.5 +/- 3.5 years) were randomly assigned to 3 groups; AR:
aerobic before resistance training, RA: resistance before aerobic training and
CON: no training. Subjects trained 2 times per week for 10 weeks. Resistance
training consisted of 3 sets of 8-12 repetitions for 5 different exercises, 70
80% of one repetition maximum (1RM). Aerobic exercise consisted of cycling at 60%
of heart rate reserve (HRR). Significant interaction effects were observed in
waist circumference (P < 0.01), grip strength (P < 0.01), 10-m walk speed (P <
0.05) and 1RM strength (P < 0.01). However, no significant differences were
observed between AR and RA. In contrast, pulse wave velocity (PWV) significantly
reduced in the RA (9.0 +/- 1.6 m/s to 8.0 +/- 1.6 m/s, P < 0.05), whereas, it did
not change in the AR, and there was a significant group difference (P < 0.05). In
conclusion, no effects of the exercise order were observed in body composition,
physical fitness and muscle strength. However, aerobic exercise after high
intensity resistance training reduced arterial stiffness and difference of
exercise order was observed. We suggest that the exercise order may favorably
affect arterial stiffness when combined aerobic exercise and high-intensity
resistance training is performed into the same session.
PMID- 29953952
TI - Cross-sectional and longitudinal associations between serum 25-hydroxyvitamin D
and anti-oxidative status in older adults.
AB - OBJECTIVE: Emerging evidence indicates that vitamin D has anti-oxidative
properties. The present study investigates whether serum 25-hydroxyvitamin D
[25(OH)D] is associated with biomarkers of anti-oxidative status in community
dwelling older adults using cross-sectional and longitudinal data. METHODS: A
total of 302 subjects aged 62 to 92 years from Germany (50.6 degrees N) were
analysed via cross-sectional approach. For longitudinal analysis, data of 153
subjects were available. Fasting blood samples from 2004 and 2012 were analysed
for 25(OH)D concentrations, total anti-oxidative status (TAOS) as well as anti
oxidative enzymes, such as catalase (CAT), glutathione peroxidase (GPx) and
superoxide dismutase (SOD). Multiple regression analyses were performed to
examine the associations between 25(OH)D and parameters of anti-oxidative status.
RESULTS: In cross-sectional analyses, 25(OH)D was a significant predictor of CAT
(beta = -0.166; P = 0.010), lg10 GPx (beta = 0.136; P = 0.037) and TAOS (beta =
0.121; P = 0.048) after adjusting for age, sex, percentage total body fat (TBF),
month of blood sampling, smoking behaviour and use of vitamin D supplements.
Longitudinal change in 25(OH)D concentration positively predicted change in TAOS
(beta = 0.224; P = 0.006) after adjusting for sex, baseline TAOS, age, smoking
behaviour, use of vitamin D supplements and change in TBF, physical activity
level, current time spent outdoors and dietary vitamin D intake. CONCLUSION: The
maintenance of an adequate vitamin D status may have a beneficial impact on the
anti-oxidative defence system in older adults on a long-term perspective.
PMID- 29953953
TI - Treating Hydrocephalus with Retrograde Ventriculosinus Shunt: Prospective
Clinical Study.
AB - BACKGROUND: Since the 1950s, hydrocephalus has been be treated with cerebrospinal
fluid (CSF) shunts, usually to the peritoneal cavity or to the right cardiac
atrium. However, because of their siphoning effect, these shunts lead to
nonphysiologic CSF drainage, with possible comorbidity and high revision rates.
More sophisticated shunt valve systems significantly increase costs and technical
complexity and remain unsuccessful in a subgroup of patients. In an attempt to
obtain physiologic CSF shunting, many neurosurgical pioneers shunted towards the
dural sinuses, taking advantage of the physiologic antisiphoning effect of the
internal jugular veins. Despite several promising reports, the ventriculosinus
shunts have not yet become standard neurosurgical practice. METHODS: In this
single-center prospective clinical study, we implanted the retrograde
ventriculosinus shunt, as advocated by El-Shafei, in 10 patients. This article
reports on our operation technique and long-term outcome, including 4 patients in
whom this shunt was implanted as a rescue operation. RESULTS: Implantation of a
ventriculosinus shunt proved to be feasible, warranting physiologic drainage of
CSF. However, in only 3 of 14 patients, functionality of the retrograde
ventriculosinus shunt was maintained during more than 6 years of follow-up. In
our opinion, these shunts fail because present venous access devices are
difficult to implant correctly and become too easily obstructed. After discussion
of possible causes of this frequent obstruction, a new dural venous sinus access
device is presented. CONCLUSION: An easy-to-implant and thrombogenic-resistant
dural venous sinus access device needs to be developed before ventriculosinus
shunting can become general practice.
PMID- 29953956
TI - An Updated History of the American Association of Gynecologic Laparoscopists
(2001-2017).
PMID- 29953957
TI - Marketing authorisation applications submitted to the European Medicines Agency
by small and medium-sized enterprises: an analysis of major objections and their
impact on outcomes.
AB - Small and medium-sized enterprises (SMEs) are an important source of innovative
medicines. Compared with their larger counterparts, they experience challenges as
a result of insufficient human and financial resources that can hamper drug
development and regulatory compliance. This analysis reviews the profile of major
objections raised in marketing authorisation applications for medicines for human
use submitted by SMEs to the European Medicines Agency (EMA) between 2011 and
2015 and their impact on the outcome of applications. It showed that SMEs
experience challenges in the quality (e.g. manufacturing process validation and
control and/or characterisation data of drug substance or drug product) and
clinical sections of marketing authorisation applications (e.g. analysis or
robustness of pivotal data or selection of submitted studies, study design issues
and marginal or no clinical relevant efficacy), with deficiencies in
demonstrating clinical efficacy representing the major eventual hurdles to
authorisation.
PMID- 29953958
TI - Macroglossia, the first manifestation of systemic amyloidosis associated with
multiple myeloma: Case report.
AB - Amyloidosis is a group of diseases characterized by an irreversible and
extracellular deposition of fibrillar, amorphous protein known as amyloid in
different organs and tissues. Amyloid deposits may occur locally in tissues or
may involve various organs, resulting in a wide range of clinical manifestations.
Amyloidosis of the head and neck is rarely seen and can reflect some plasma cell
dyscrasia that affects B lymphocytes. Deposition of amyloid on the tongue is very
rare and accounts for less than 9% of all types of amyloidosis. Amyloid
involvement of the tongue is almost always secondary to systemic amyloidosis. We
report a 73-year-old female who presented with weight loss and macroglossia.
Firstly, she was diagnosed only with amyloidosis of the tongue. Her general
health condition was evaluated, revealing renal dysfunction, anemia,
hypercalcemia, and hyperphosphatemia. The final diagnosis was systemic
amyloidosis with multiple myeloma. The patient was referred for emergency
hemodialysis and chemotherapy. Her condition progressed to congestive heart
failure and recurrent urinary and respiratory infections. After 100 days from
diagnosis, the patient died by pulmonary infection as a consequence of her
weakened state of health. It is important to highlight role of the dentist
especially oral pathologist to the evaluation of local alterations that may
reflect systemic deterioration of patients.
PMID- 29953955
TI - Electrophysiological features and radiofrequency catheter ablation of
supraventricular tachycardia in patients with persistent left superior vena cava.
AB - BACKGROUND: The electrophysiological features and roles of persistent left
superior vena cava (PLSVC) in supraventricular tachycardia (SVT) are not known.
OBJECTIVE: The purpose of this study was to elucidate the electrophysiological
features and roles of PLSVC in patients with SVT. METHODS: We included 37
patients with PLSVC (mean age 43.5 +/- 17.1 years; 35.1% men) and 510 patients
without PLSVC (mean age 43.9 +/- 18.8 years; 48.2% men) who underwent an
electrophysiology study for SVT. The number of induced tachycardias, location of
the slow pathway (SP) or accessory pathway (AP), and radiofrequency catheter
ablation (RFCA) outcomes were compared between patients with and without PLSVC.
During RFCA of the left AP, a coronary sinus (CS) catheter was placed into the
left superior vena cava (left superior vena cava group) or the great cardiac vein
(great cardiac vein group). The RFCA outcomes were compared between the groups.
RESULTS: In patients with PLSVC, 40 tachycardias were induced: atrioventricular
nodal reentrant tachycardia (AVNRT) (n = 19), atrioventricular reentrant
tachycardia (n = 17), and focal atrial tachycardia (n = 4). Among patients with
AVNRT, an SP in the CS was significantly more frequent in patients with PLSVC
than in those without PLSVC (47.4% vs 3.8%; P < .001). In patients with the left
AP, the number of RFCA attempts and recurrence were lower in the great cardiac
vein group than in the left superior vena cava group. CONCLUSION: An SP in the CS
is prevalent in patients with AVNRT and PLSVC. It is useful to place a CS
catheter into the great cardiac vein in patients with a left AP and PLSVC.
PMID- 29953959
TI - Effects of manganese toxicity on the protein profile of tomato (Solanum
lycopersicum) roots as revealed by two complementary proteomic approaches, two
dimensional electrophoresis and shotgun analysis.
AB - The aim of this work was to assess the effects of manganese (Mn) toxicity on the
proteome of tomato roots using two proteomic approaches, shotgun and two
dimensional electrophoresis. The shotgun approach yielded 367 reliable proteins,
whereas the 2-DE approach detected 340 consistent spots. The 2-DE method found 54
proteins changing in relative abundance in the excess Mn treatment, whereas the
shotgun detected changes in 118 proteins. Only 7% of the differential proteins
were found by both methods, illustrating their complementary nature. Metabolic
pathways most affected were protein metabolism, oxido-reductases and signaling.
Results support that Mn toxicity alters the protein turnover and impairs energy
production in roots, leading to changes in glycolysis, pyruvate metabolism, TCA
and oxidative phosphorylation. Excess Mn also induced changes in peroxidases and
hydrolases participating in cell wall lignification and suberization and
activated plant defense mechanisms, with changes occurring via pathogenesis
related proteins as well as peroxidases. Finally, Mn toxicity elicited regulatory
mechanisms and affected the abundance of root nutrient reservoir proteins. The
overall analysis of the differential root proteome upon Mn toxicity suggests a
general slowdown of metabolic activities, especially energy production, cell wall
integrity and protein turnover, which occurs in parallel with increases in stress
related proteins.
PMID- 29953954
TI - Progression of electrocardiographic abnormalities associated with initial
ventricular fibrillation in asymptomatic patients with Brugada syndrome.
AB - BACKGROUND: Various risk stratifications in asymptomatic patients with Brugada
syndrome (BrS) have been proposed, but the electrophysiological change that
promotes ventricular fibrillation (VF) is still unknown. OBJECTIVE: The aim of
this study was to clarify the changes in electrocardiographic (ECG) markers at
the onset of VF from ECGs recorded when patients were still asymptomatic.
METHODS: The subjects of this study included 14 patients with VF and 48
consecutive asymptomatic patients with BrS. We compared ECGs before the initial
VF events (>6 months; early phase) with ECGs at the initial VF events (late
phase). In asymptomatic patients, we evaluated ECGs at 2 time points with an
interval of >6 months. We evaluated various ECG markers including type 1 ECG and
fragmented QRS (fQRS; multiple spikes within the QRS complex). RESULTS: ECG
parameters of the early and late phases were not different except for decreased
ST voltage and low incidence of type 1 ECG in asymptomatic patients. There were
no differences in ECG parameters of the early phase between patients with VF and
asymptomatic patients. In patients with VF, ECGs at the late phase had longer QRS
intervals and intervals between the peak and the end of the T wave and more
frequent type 1 ECG and fQRS than did ECGs at the early phase. Those changes were
associated with initial VF events (QRS widening: odds ratio [OR] 11.5, P < .01;
interval between the peak and the end of the T wave: OR 11.6, P < .01; fQRS: odds
ratio 15.3, P < .01; type 1 ECG: OR 6.6, P < .05). CONCLUSION: QRS and ST-T wave
abnormalities developed in association with the initial VF events. Aggravation of
the conduction disturbance in addition to BrS-ECG promotes VF.
PMID- 29953960
TI - Exosomes derived from calcium oxalate-exposed macrophages enhance IL-8 production
from renal cells, neutrophil migration and crystal invasion through extracellular
matrix.
AB - Deposition of calcium oxalate (CaOx) crystals in renal interstitium is one of the
key factors that cause progressive inflammation in kidney stone disease.
Macrophages are responsible for elimination of these crystals but their roles to
worsen inflammatory process remain under-investigated. This study thus aimed to
define roles of exosomes released from macrophages exposed to CaOx crystals in
mediating subsequent inflammatory cascades. Macrophages were incubated with or
without CaOx monohydrate (COM) crystals for 16 h and their exosomes were
isolated. Quantitative proteomics using nanoLC-ESI-Qq-TOF MS/MS revealed 26
proteins with significantly altered levels in exosomes derived from COM-treated
macrophages (COM-treated exosomes) comparing to those derived from the controlled
macrophages (controlled exosomes). Protein network analysis showed that these
altered proteins were involved in cytoskeleton and actin binding, calcium
binding, stress response, transcription regulation, immune response and
extracellular matrix disassembly. Functional investigations revealed that COM
treated exosomes enhanced IL-8 production from renal tubular cells, activated
neutrophil migration, had increased (exosomal) membrane fragility, had greater
binding capacity to COM crystals, and subsequently enhanced crystal invasion
through extracellular matrix migration chamber. These data indicate that
macrophage exosomes play important roles in inflammatory response to COM crystals
and may be involved in crystal invasion in the renal interstitium.
PMID- 29953961
TI - Long-term moderate exercise enhances specific proteins that constitute
neurotrophin signaling pathway: A TMT-based quantitative proteomic analysis of
rat plasma.
AB - : Physical exercise has been reported to increase neurotrophin in brain tissues
as hippocampus as well as increased neurotrophic level peripherally in blood
plasma and might have an effect on/or affect molecular processes of energy
metabolism (and homeostasis). In this study, using quantitative proteomic
analysis, we obtained a plasma protein profile from the rat with long-term
moderate exercise. A total of 752 proteins were identified in the plasma. Among
them, 54 proteins were significant up-regulated and 47 proteins were down
regulated in the plasma of exercise group compared with the control group.
Bioinformatic analyses showed that these altered proteins are widely involved in
multiple biological processes, molecular functions and cellular components, which
connect with 11 signaling pathways. Interestingly, 5 up-regulated proteins Rap1b,
PTPN11, ARHGDIA, Cdc42 and YWHAE, confirmed by Western blots, are involved in the
neurotrophin signaling pathway which shows the lowest P value among the
identified pathways. Further analyses showed that the 5 neurotrophin-signaling
pathway-related proteins participate in two important protein-protein interaction
networks associated to cell survival and apoptosis, axonal development, synapse
formation and plasticity. This study provides an exercise-induced plasma protein
profile, suggesting that long-term exercise enhances the proteins involved in
neurotrophin signaling pathway which may contribute to health benefit.
SIGNIFICANCE: Physical activity contributes to myriad benefits on body health
across the lifespan. The changes in plasma proteins after chronic moderate
exercise may be used as biomarkers for health and may also play important roles
in increase of cardiovascular fitness, enhancement of immune competence,
prevention of obesity, decrease of risk for neurological disorders, cancer,
stroke, diabetes and other metabolic disorders. Using a TMT-based proteomic
method, this study identified 101 altered proteins in the plasma of rats after
long-term moderate treadmill running, which may provide novel biomarkers for
further investigation of the underlying mechanism of physical exercise. We
confirmed that exercise enhances 5 proteins of the neurotrophin signaling pathway
that may contribute to health benefits.
PMID- 29953962
TI - Probing the colorectal cancer proteome for biomarkers: Current status and
perspectives.
AB - Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide.
Biomarkers that can facilitate better clinical management of CRC are in high
demand to improve patient outcome and to reduce mortality. In this regard,
proteomic analysis holds a promising prospect in the hunt of novel biomarkers for
CRC and in understanding the mechanisms underlying tumorigenesis. This review
aims to provide an overview of the current progress of proteomic research,
focusing on discovery and validation of diagnostic biomarkers for CRC. We will
summarize the contributions of proteomic strategies to recent discoveries of
protein biomarkers for CRC and also briefly discuss the potential and challenges
of different proteomic approaches in biomarker discovery and translational
applications.
PMID- 29953963
TI - A large-scale and robust dynamic MRM study of colorectal cancer biomarkers.
AB - : Over the past 20 years, mass spectrometry (MS) has emerged as a dynamic tool
for proteomics biomarker discovery. However, published MS biomarker candidates
often do not translate to the clinic, failing during attempts at independent
replication. The cause can be shortcomings in study design, sample quality, assay
quantitation, and/or quality/process control. To address these shortcomings, we
developed an MS workflow in accordance with Tier 2 measurement requirements for
targeted peptides, defined by the Clinical Proteomic Tumor Analysis Consortium
(CPTAC) "fit-for-purpose" approach, using dynamic multiple reaction monitoring
(dMRM), which measures specific peptide transitions during predefined retention
time (RT) windows. We describe the development of a robust multipex dMRM assay
measuring 641 proteotypic peptides from 392 colorectal cancer (CRC) related
proteins, and the procedures to track and handle sample processing and instrument
variation over a four-month study, during which the assay measured blood samples
from 1045 patients with CRC symptoms. After data collection, transitions were
filtered by signal quality metrics before entering receiver operating
characteristic (ROC) analysis. The results demonstrated CRC signal carried by 127
proteins in the symptomatic population. The workflow might be further developed
to build Tier 1 assays for clinical tests identifying symptomatic individuals at
elevated risk of CRC. SIGNIFICANCE: We developed a dMRM MS method with the rigor
of a Tier 2 assay as defined by the CPTAC 'fit for purpose approach' [1]. Using
quality and process control procedures, the assay was used to quantify 641
proteotypic peptides representing 392 CRC-related proteins in plasma from 1045
CRC-symptomatic patients. To our knowledge, this is the largest MRM method
applied to the largest study to date. The results showed that 127 of the proteins
carried univariate CRC signal in the symptomatic population. This large number of
single biomarkers bodes well for future development of multivariate classifiers
to distinguish CRC in the symptomatic population.
PMID- 29953964
TI - Assessing the Accuracy of Variant Detection in Cost-Effective Gene Panel Testing
by Next-Generation Sequencing.
AB - There is significant debate within the diagnostics community regarding the
accuracy of variant identification by next-generation sequencing and the
necessity of confirmatory testing of detected variants. Because the quality
threshold to discriminate false positives depends on the workflow, no regulatory
standard regarding this matter has yet been published. The goal of this study was
to empirically determine the threshold to perform additional Sanger sequencing
and to reduce the experimental cost to a practical level. Using 278 model genes,
a hybridization capture-based protocol was examined to meet the clinical
requirements of low cost, high efficiency, and high-quality data. To reduce
excessive false-positive detection, filtering processes were introduced to remove
mismapped reads and strand-biased detection to a published best-practices
pipeline. With seven samples from the 1000 Genomes Project, 2750 single
nucleotide polymorphisms and 142 insertions/deletions were identified by our
designed workflow. Compared with variants registered in the single nucleotide
polymorphism database (dbSNP), a zero false-positive threshold value was
determined (quality score > 1000). The variants satisfying these criteria
accounted for 95.6% of single-nucleotide polymorphisms and 50.7% of
insertions/deletions. Except for deletions located within the highly repeated
sequences, the workflow achieved 100% sensitivity. The established threshold
allowed us to discriminate between convincing variants and those requiring
validation, a design that reconciles the competing objectives of cost
minimization and quality maximization of clinical gene panel testing.
PMID- 29953965
TI - MicroRNA-17 inhibition overcomes chemoresistance and suppresses epithelial
mesenchymal transition through a DEDD-dependent mechanism in gastric cancer.
AB - MicroRNAs (miRNAs), a novel class of important gene-regulatory molecules,
correlates with tumor growth, invasion, metastasis, and chemo resistance in
gastric cancer (GC). Microarray analysis revealed that aberrant expressed
microRNA-17 (miR-17) and DEDD were identified in GC. DEDD has been found to act
as an endogenous suppressor of tumor growth and metastasis through epithelial
mesenchymal transition (EMT) process. However, the role of miRNA-17 (miR-17) has
not been clearly evaluated in GC, thereby a series of in vitro experiments were
performed in this study. The levels of miR-17 and DEDD in GC tissues from
patients diagnosed with GC and in five GC cell lines (SGC-7901, MKN-45, HGC-27,
BGC823, and AGS) were detected. It was found that miR-17 up-regulated and DEDD
down-regulated in GC, and SGC-7901 and AGS cells were adopted for the in vitro
cell experiments, in which the expression of miR-17 or DEDD was regulated by
transfection. DEDD was validated to be a target gene of miR-17. Inhibition of miR
17 impaired EMT in GC cells. In addition, transwell assay and scratch test
results revealed that inhibition of miR-17 hindered GC cell invasion and
migration. Moreover, inhibition of miR-17 reduced resistance to cisplatin- or 5
Fu in GC cells and induced cisplatin- or 5-Fu-treated GC cell apoptosis, which
evaluated by using CCK-8 and flow cytometry assays. From the short review above,
the key findings emerge that inhibition of miR-17 may have tumor suppressive
effects on GC and enhance its chemosensitivity by promoting DEDD, highlighting a
novel target for GC therapy.
PMID- 29953966
TI - New fluorescently labeled auxins exhibit promising anti-auxin activity.
AB - The plant hormone auxin is a key player in the regulation of plant growth and
development. Despite numerous studies devoted to understanding its role in a wide
spectrum of physiological processes, full appreciation of its function is linked
to a comprehensive determination of its spatio-temporal distribution, which plays
a crucial role in its mode of action. Conjugation of fluorescent tracers to plant
hormones enables sensitive and specific visualization of their subcellular and
tissue-specific localization and transport in planta, which represents a powerful
tool for plant physiology. However, to date, only a few fluorescently labeled
auxins have been developed. We report the synthesis of four novel fluorescently
labeled derivatives of indole-3-acetic acid (IAA) in the form of a conjugate with
a nitrobenzoxadiazole (NBD) fluorophore together with validation of their
biological activity. These compounds, unlike other previously reported auxins
fluorescently labeled at N1 position (nitrogen of the indole ring), do not
possess auxin activity but rather show dose-dependent inhibition of auxin-induced
effects, such as primary root growth inhibition, root hair growth and the auxin
reporter DR5::GUS expression. Moreover, the study demonstrates the importance of
the character of the linker and optimal choice of the labeling site in the
preparation of fluorescently labeled auxins as important variables influencing
their biological activity and fluorescent properties.
PMID- 29953967
TI - Statin therapy improved long-term prognosis in patients with major non-cardiac
vascular surgeries: a systematic review and meta-analysis.
AB - OBJECTIVE: To investigate whether statin intervention will improve the long-term
prognosis of patients undergoing major non-cardiac vascular surgeries. METHODS:
Major database searches for clinical trials enrolling patients undergoing major
non-cardiac vascular surgeries, including lower limb revascularization, carotid
artery surgeries, arteriovenous fistula, and aortic surgeries, were performed.
Subgroup analyses, stratified by surgical types or study types, were employed to
obtain statistical results regarding survival, patency rates, amputation, and
cardiovascular and stroke events. Odds ratio (ORs) and 95% confidence intervals
(CIs) were calculated by Review Manager 5.3. Sensitivity analysis, publication
bias and meta-regression were conducted by Stata 14.0. RESULTS: In total, 34
observational studies, 8 prospective cohort studies and 4 randomized controlled
clinical trials (RCTs) were enrolled in the present analysis. It was demonstrated
that statin usage improved all-cause mortality in lower limb, carotid, aortic and
mixed types of vascular surgery subgroups compared with those in which statins
were not used. Additionally, the employment of statins efficiently enhanced the
primary and secondary patency rates and significantly decreased the amputation
rates in the lower limb revascularization subgroup. Furthermore, for other
complications, statin intervention decreased cardiovascular events in mixed types
of vascular surgeries and stroke incidence in the carotid surgery subgroup. No
significant publication bias was observed. The meta-regression results showed
that the morbidity of cardiovascular disease or the use of aspirin might affect
the overall estimates in several subgroups. CONCLUSIONS: This meta-analysis
demonstrated that statin therapy was associated with improved survival rates and
patency rates and with reduced cardiovascular or stroke morbidities in patients
who underwent non-cardiac vascular surgeries.
PMID- 29953968
TI - Sutureless Pars Plana Vitrectomy for Intraocular Foreign Bodies.
PMID- 29953969
TI - Identification of Prognostic Value of Rs3735590 Polymorphism in 3'-Untranslated
Region (3'-UTR) of Paraoxonase 1 (PON-1) in Chronic Obstructive Pulmonary Disease
Patients who Received Coronary Artery Bypass Grafting (CABG).
AB - BACKGROUND/AIMS: In the treatment of serious and symptomatic coronary heart
disease (CHD), coronary artery bypass grafting (CABG) is a frequently utilized
intervention. In addition, the risk of CHD is strongly associated with the low
activity of paraoxonase-1 (PON1), whose 3'-UTR harbors an rs3735590 polymorphism.
The aim of this study was to investigate whether the rs3735590 polymorphism could
be used as a prognosis marker in chronic obstructive pulmonary disease (COPD)
patients undergoing CABG. In addition, the hypothesis, i.e., the rs3735590
polymorphism may be involved in the regulation of PON1 gene expression via
modulating its interaction with miRNAs, was tested in this study. METHODS: 292
patients diagnosed with COPD and treated with CABG were recruited for this study.
Genomic DNA was extracted from clinical samples, and real-time quantitative PCR
and Western-blot were used to measure the expression of miR-616 and PON1 in liver
cells of different genotypes. RESULTS: 292 COPD patients were divided into three
groups according to their genotypes, i.e., rs3735590: CC (212), TC (75), and TT
(5), respectively (TC and TT were merged in one group of T carriers for
statistical analyses). Patients with the CC genotype were associated with a
shorter event-free survival time as compared to patients with the T genotypes. In
addition, PON1 was confirmed as a direct target gene of miR-616, while
experiments with primary cells of different genotypes showed that miR-616
inhibited the expression of PON1 in CC cells. On the contrary, rs3735590 impaired
such inhibitory effect of miR-616 in TT cells. CONCLUSION: The rs3735590
polymorphism of PON1 acts as a prognostic biomarker in COPD patients treated by
CABG.
PMID- 29953970
TI - Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin
Receptor and PDGFR-beta/STAT3 Pathway.
AB - BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most
lethal malignant tumors with poor prognosis. Conventional chemotherapies
including gemcitabine have failed owing to weak response and side effects. Hence
novel treatment regimens are urgently needed to improve the therapeutic efficacy.
In this study, we aimed to assess the anticancer activity of melatonin and
sorafenib as a novel therapy against PDAC. METHODS: We used various apoptosis
assay and PDAC xenograft model to assess anticancer effect in vitro and in vivo.
We applied phospho-receptor tyrosine kinase (RTK) array and phospho-tyrosine
kinase array to explore the mechanism of the combined therapy. Western blotting,
proximity ligation assay, and immunoprecipitation assay were also performed for
validation. RESULTS: Melatonin synergized with sorafenib to suppress the growth
of PDAC both in vitro and in vivo. The effect was due to increased apoptosis rate
of PDAC cells that was accompanied by mitochondria dysfunction. The enhanced
anticancer efficacy by the co-treatment could be explained by blockade of PDGFR
beta/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3.
CONCLUSIONS: Melatonin reinforces the anticancer activity of sorafenib by
downregulation of PDGFR-beta/STAT3 signaling pathway and melatonin receptor (MT)
mediated STAT3. The combination of the two agents might be a potential
therapeutic strategy for treating PDAC.
PMID- 29953971
TI - Multimorbidity Is Associated with Preclinical Alzheimer's Disease Neuroimaging
Biomarkers.
AB - BACKGROUND: Identifying comorbidities that influence preclinical Alzheimer's
disease (AD) can give some insight into the AD early stages trajectories to allow
new treatment venues and to guide public health systems to prevent subsequent
dementia. OBJECTIVE: To examine the association of multimorbidity with AD
neuroimaging markers in cognitively normal older adults. METHODS: This study had
a cross-sectional design. Data regarding 14 comorbidities were obtained for all
318 adults aged 70-85 years, recruited from the community to an ongoing
prospective monocentric cohort. They underwent standardized neuropsychological
and neuroimaging assessment with automated methods that measured hippocampal
volumes, white matter hyperintensity volumes, fluorodeoxyglucose positron
emission tomography (FDG-PET) standardized uptake values (SUV) in AD signature
regions, and amyloid positron emission tomography (amyloid-PET) SUV ratios.
Linear regression was used to assess the association of multimorbidity with AD
neuroimaging biomarkers. RESULTS: Multimorbidity is signif icantly associated
with lower hippocampal volumes (-0.03 +/- 0.01; p = 0.012; R2 = 0.017) and lower
FDG-PET SUV (-0.027 +/- 0.009; p = 0.005; R2 = 0.022), with no association with
amyloid deposition (0.001 +/- 0.007; p = 0.884; R2 = 0.0001). Taken individually,
obesity and excessive alcohol use are associated with lower FDG-PET values,
whereas obstructive sleep apnea and mood disorders are related to lower amyloid
PET SUV ratios. CONCLUSION: Multimorbidity is associated with preclinical AD
imaging markers of neurodegeneration, but not with amyloid.
PMID- 29953972
TI - Resistant Paediatric Somatotropinomas due to AIP Mutations: Role of Pegvisomant.
AB - BACKGROUND: Somatotropinomas are rare in childhood and frequently associated with
genetic mutations. AIP mutations are found in 20-25% cases and cause aggressive
somatotropinomas, often resistant to somatostatin analogues. AIMS: To assess
responses to multimodal therapy including pegvisomant in 2 children with sporadic
somatotropinomas due to AIP mutations. CASE DESCRIPTION: We report 2 children, a
boy aged 13 and a girl aged 10, with rapid growth, visual impairment, and growth
hormone hypersecretion. Magnetic resonance imaging confirmed a pituitary
macroadenoma with parasellar extension in both. Despite multiple surgical
attempts to debulk tumour mass, residual tumour persisted. Genetic analysis
showed two different AIP mutations (patient 1: c.562delC [p.Arg188Glyfs*8];
patient 2: c.140_ 163del24 [p.Gly47_Arg54del8]). They were initially treated with
a long-acting somatostatin analogue (octreotide LAR 30 mg/month) and cabergoline
as a dopamine agonist, with the later addition of pegvisomant titrated up to 20
mg/day and with radiotherapy for long-term control. Somatostatin analogue was
ceased due to patient intolerance and lack of control. Patient 1 had
normalization of insulin-like growth factor-1 (IGF-1) after 5 months of combined
therapy with pegvisomant and cabergoline. For patient 2, normalization of IGF-1
was achieved after 2 months of cabergoline and pegvisomant. CONCLUSION: AIP
associated tumours can be resistant to management with somatostatin analogues.
Pegvisomant can safely be used, to normalize IGF-1 levels and help control
disease.
PMID- 29953973
TI - Late Cochlear Implantation in Early-Deafened Adults: A Detailed Analysis of
Auditory and Self-Perceived Benefits.
AB - OBJECTIVES: It is known that early-deafened cochlear implant (CI) users are a
very heterogeneously performing group. To gain more insight into this population,
this study investigated (1) postoperative changes in auditory performance over
time based on various outcome measures, focusing on poor performers, (2) self
perceived outcomes, (3) relations between auditory and self-perceived outcomes,
and (4) preimplantation factors predicting postoperative outcomes. METHODS:
Outcomes were assessed prospectively in a group of 27 early-deafened, late
implanted CI users, up to 3 years after implantation. Outcome measures included
open-set word and sentence recognition, closed-set word recognition, speech
tracking and a questionnaire on self-perceived outcomes. Additionally, the
relative influence of 8 preimplantation factors on CI outcome was assessed with
linear regression analyses. RESULTS: Significant improvements were found for
auditory performance measures and most of the questionnaire domains. Significant
changes of the closed-set word test, speech tracking and questionnaire were also
found for a subgroup of poor performers. Correlations between auditory and self
perceived outcomes were weak and nonsignificant. Preoperative word recognition
and preoperative hearing thresholds, both for the implanted ear, were significant
predictors of postoperative outcome in the multivariable regression model,
explaining 63.5% of the variation. CONCLUSIONS: Outcome measurement in this
population should be adjusted to the patients' individual performance level and
include self-perceived benefit. There is still a need for more knowledge
regarding predictors of CI outcomes in this group, but the current study suggests
the importance of the preoperative performance of the ear to be implanted.
PMID- 29953974
TI - Etoricoxib and Diclofenac Might Reduce the Risk of Dementia in Patients with
Osteoarthritis: A Nation-Wide, Population-Based Retrospective Cohort Study.
AB - INTRODUCTION: This population-based cohort study investigates the association
between osteoarthritis (OA) and dementia as well as the connection between NSAIDs
and dementia. METHODS: We chose the samples from the Taiwan Longitudinal Health
Insurance Database and then divided them into two groups, which were then matched
1: 1 by propensity score. The first group was the OA group that contained
patients with newly diagnosed OA and the second group was the non-OA group. We
used the chi2 test, Student t test, Kaplan-Meier analysis, and Cox proportional
hazard model for different purposes. RESULTS: The prevalence of dementia in the
OA group was higher than that in the non-OA group. The adjusted hazard ratio of
the former was 1.42 (95% CI, 1.30-1.54). We also found that etoricoxib and
diclofenac might reduce the incidence of dementia. CONCLUSION: Patients with OA
might have a higher risk of dementia. Both etoricoxib and diclofenac might lower
the risk of dementia in patients with OA.
PMID- 29953975
TI - Gremlin1 Delivered by Mesenchymal Stromal Cells Promoted Epithelial-Mesenchymal
Transition in Human Esophageal Squamous Cell Carcinoma.
AB - : Backgroud/Aims: Mesenchymal stromal cells (MSCs) are a major component of the
tumor microenvironment (TME). Several studies focusing on tumor-derived MSCs have
demonstrated that they exhibit a strong ability to promote the tumor epithelial
mesenchymal transition (EMT). However, the factors mediating these effects are
poorly understood. METHODS: Quantitative reverse transcription-polymerase chain
reaction (qRT-PCR) and immunohistochemistry assays were used to detect the
expression of Gremlin1 (GREM1) in human esophageal squamous cell carcinoma (ESCC)
tissues. ShRNA silencing, flow cytometry, cell counting kit (CCK8) assay,
invasion assay, western blot were used to detect the effect of GREM1 in ECa109,
TE-1 cell lines and xenograft tumor models. RESULTS: In the current study, we
found that the GREM1 was overexpressed in human ESCC tissues. The conditioned
medium from mesenchymal stromal cells (MSCs-CM) enhanced the malignancy of
xenograft esophageal tumors in vivo, as well as the cell proliferation, viability
and invasion of the esophageal carcinoma cell lines ECa109 and TE-1 in vitro.
Furthermore, the shRNA silencing of GREM1 in MSCs (shGREM1-MSCs) reversed the
increased malignancy of the esophageal tumor in vivo, while the conditioned
medium from shGREM1-MSCs (shGREM1-MSCs-CM) affected the cell cycle and cell
invasion in vitro. These processes were accompanied by the EMT in the ECa109 and
TE-1 cell lines with an alteration in the expression levels of mesenchymal and
epithelial markers. Furthermore, the TGF-beta/BMP (transforming growth factor
beta/bone morphogenetic protein) signaling pathway participated in the shGREM1
MSCs-CM-induced anti-tumor effect on enhanced esophageal malignancy induced by
MSCs-CM treatment. CONCLUSIONS: Taken together, our study suggested that GREM1
delivered by MSCs promoted EMT in ESCC in vitro and in vivo, which is partly
through TGF-beta/BMP signaling pathway. The results provide experimental evidence
to a potential therapeutic target in the treatment of esophageal cancer.
PMID- 29953976
TI - Chronically Hypoxic Fetal Lambs Supported by an Extra-Uterine Device Exhibit
Mitochondrial Dysfunction and Elevations of Hypoxia Inducible Factor 1-Alpha.
AB - INTRODUCTION: We have recently developed an extra-uterine environment for
neonatal development (EXTEND) capable of supporting premature fetal lambs and
have been able to replicate hypoxic in utero conditions by controlling fetal
oxygen delivery. In this study, we investigated the fetal mitochondrial response
to hypoxia. METHODS: Eight premature fetal lambs were delivered via hysterotomy
and transitioned to extra-uterine support for 3 weeks. The lambs were divided
into 2 groups: normoxic fetuses which maintained physiologic oxygen delivery and
hypoxic fetuses in which oxygen delivery was significantly reduced. Control
fetuses were delivered via hysterotomy but not cannulated. Measurements of
mitochondrial membrane potential (MMP) were performed in peripheral blood
mononuclear cells. RESULTS: There were no significant differences in MMP between
normoxic EXTEND fetuses and controls. Hypoxic fetuses had significantly more
depolarized mitochondria compared to normoxic fetuses overall, and these changes
were specifically appreciated in weeks 1 and 2, but not by week 3. Hypoxic
fetuses had significantly elevated levels of HIF-1alpha compared to normoxic
fetuses in the first 2 weeks. DISCUSSION: Normoxic fetal lambs supported by
EXTEND demonstrate normal mitochondrial function as evidenced by equivalent
membrane potentials compared to control fetuses. Hypoxic fetuses exhibit
mitochondrial dysfunction, though they do show evidence of adaptation after 3
weeks of hypoxic exposure.
PMID- 29953977
TI - A Novel Approach to Estimate ROS Origination by Hyperbaric Oxygen Exposure,
Targeted Probes and Specific Inhibitors.
AB - BACKGROUND/AIMS: Reactive oxygen species (ROS) are considered fundamental in
various physiological/pathophysiological processes and prevention/treatment
measures such as hyperbaric oxygen (HBO) therapy. In this study, the origination
of ROS in human umbilical vein endothelial cells was investigated under basal and
HBO conditions. METHODS: Whole cell or mitochondria-targeted fluorescent probes
were applied to mark superoxide anion (O2-), and the ROS produced from
mitochondrial respiratory chain (MRC), NADPH oxidase (NOX) and xanthine oxidase
(XO) were identified by flow cytometry, confocal imaging and microplate
fluorometry with or without specific inhibitors. An algorithm was established to
calculate ROS proportion of each source. RESULTS: HBO increased ROS to about 2.14
2.44 fold in mitochondria and 1.32-1.42 fold in whole cell. Then ROS levels were
significantly decreased by MRC inhibition about 30% and 16%, respectively. NOX or
XO inhibition did not affect HBO-induced ROS generation. Based on these data, it
could be further estimated that mitochondrial ROS accounted for 32%-39% of basal
whole-cell ROS including 3% from MRC complex II, and NOX accounted for at least
24%-29%. Following HBO treatment, almost all increased ROS originated from
mitochondria, and MRC complex II contributed at least 45%-60%. CONCLUSION: This
study provided a simple but effective method to estimate the origination of
intracellular ROS and found that MRC were the main source of HBO-induced ROS
generation.
PMID- 29953978
TI - A Volumetric Analysis of the Vocal Tract Associated with Laryngectomees Using
Acoustic Reflection Technology.
AB - OBJECTIVE: Previous studies of the laryngectomized vocal tract using formant
frequencies reported contradictory findings. Imagining studies of the vocal tract
in alaryngeal speakers are limited due to the possible radiation effect as well
as the cost and time associated with the studies. The present study examined the
vocal tract configuration of laryngectomized individuals using acoustic
reflection technology. SUBJECTS AND METHODS: Thirty alaryngeal and 30 laryngeal
male speakers of Cantonese participated in the study. A pharyngometer was used to
obtain volumetric information of the vocal tract. All speakers were instructed to
imitate the production of /a/ when the length and volume information of the oral
cavity, pharyngeal cavity, and the entire vocal tract were obtained. The data of
alaryngeal and laryngeal speakers were compared. RESULTS: Pharyngometric
measurements revealed no significant difference in the vocal tract dimensions
between laryngeal and alaryngeal speakers. CONCLUSION: Despite the removal of the
larynx and a possible alteration in the pharyngeal cavity during total
laryngectomy, the vocal tract configuration (length and volume) in
laryngectomized individuals was not significantly different from laryngeal
speakers. It is suggested that other factors might have affected formant measures
in previous studies.
PMID- 29953979
TI - Gait Variability Can Predict the Risk of Cognitive Decline in Cognitively Normal
Older People.
AB - BACKGROUND: The aim of this study was to investigate the association of gait
speed and gait variability, an index of how much gait parameters, such as step
time, fluctuate step-to-step, with risk of cognitive decline in cognitively
normal elderly individuals. While high gait variability is emerging as an early
indicator of dementing illnesses, there is little research on whether high gait
variability predicts cognitive decline in cognitively normal elderly who have no
evidence of cognitive impairment. METHODS: In this 4-year prospective cohort
study on 91 community-dwelling cognitively normal elderly individuals without
cerebral ischemic burden or Parkinsonism, we evaluated gait speed and step time
variability using a tri-axial accelerometer placed on the center of body mass,
and diagnosed mild cognitive impairment (MCI) according to the International
Working Group on MCI. We performed Kaplan-Meier analysis with consecutive log
rank testing for MCI-free survival by cohort-specific tertiles of gait speed;
hazard ratios (HR) of incident MCI were estimated using Cox proportional hazards
regression analysis adjusted for age, sex, education level, Cumulative Illness
Rating Scale score, GDS score, and presence of the apolipoprotein E epsilon4
allele. RESULTS: Out of the 91 participants in the baseline assessment, 87
completed one or more 2-year follow-up assessments, and the median duration of
follow-up was 47.1 months. Kaplan-Meier curves of incident MCI show evident
differences in risk by gait variability group (chi2 = 9.64, p = 0.002, log-rank
test). Mean MCI-free survival in the high variability group was 12% shorter than
in the mid-to-low tertile group (47.4 +/- 1.74 [SD] vs. 54.04 +/- 0.52 months),
while it was comparable between gait speed groups (51.59 +/- 0.70 vs. 50.64 +/-
1.77 months; chi2 = 1.16, p = 0.281). In multivariate analysis, subjects with
high gait variability showed about 12-fold higher risk of MCI (HR = 11.97, 95% CI
= 1.29-111.37) than those with mid-to-low variability. However, those with slow
gait speed showed comparable MCI risk to those with mid-to-high speed (HR = 5.04,
95% CI = 0.53-48.18). CONCLUSIONS: Gait variability may be a better predictor of
cognitive decline than gait speed in cognitively normal elderly individuals
without cerebral ischemic burden or Parkinsonism.
PMID- 29953980
TI - Repression of WT1-Mediated LEF1 Transcription by Mangiferin Governs beta-Catenin
Independent Wnt Signalling Inactivation in Hepatocellular Carcinoma.
AB - BACKGROUND/AIMS: The development of hepatocellular carcinoma (HCC) is a complex
process which involves deregulation of multiple signalling pathways. The hyper
activation of Wnt signalling promotes sustained expansion, invasion, and
neovascularization of HCC. Mangiferin, a natural small molecule present in
Mangifera indica L. has been shown to inactivate beta-catenin, which is an
indispensable regulator in Wnt pathway. Our study aimed to determine whether
mangiferin has any inhibitory effect on HCC and examine how it modulates Wnt
signalling. METHODS: The tumour inhibitory effect of mangiferin was examined by
in vitro cellular models and an in vivo orthotopic HCC implantation model. The
genes responsible for mangiferin-mediated anti-HCC were delineated by polymerase
chain reaction (PCR) microarray. The expression of target genes was further
determined by quantitative PCR and immuno-blotting assays. The binding capacity
of Wilms' tumour 1 (WT1) to the lymphoid enhancer-binding factor 1 (LEF1)
promoter was confirmed by chromatin immunoprecipitation-qPCR. RESULTS: Oral
administration of mangiferin inhibited orthotopic tumour growth. Cellular
investigations confirmed the dose-dependent inhibition of mangiferin on HCC
expansion and invasion. PCR array combined with Gene Ontology analysis revealed
that the Wnt pathway was the predominant target of mangiferin and LEF1 was the
most reduced gene in the Wnt pathway. Overexpression of LEF1 diminished
repression of Wnt signalling and reduced proliferation activity in mangiferin
treated HCC cells. The mangiferin-mediated down-regulation of LEF1 was
independent of beta-catenin but associated with WT1 protein. WT1 knock-in in HCC
cells further enhanced LEF1 expression. Chromatin immunoprecipitation assays
revealed that the mangiferin induced repression of LEF1 was associated with
decreased occupancy of WT1 on the LEF1 promoter. CONCLUSION: Our study identifies
a novel mechanism of hepatocellular carcinoma inhibition through beta-catenin
independent Wnt signalling, which is regulated by WT1-associated LEF1 repression.
The study also highlights mangiferin as a promising Wnt inhibitor for HCC
treatment.
PMID- 29953982
TI - A Rare Case of Pediatric Bullous Spontaneous Acute Urticaria.
AB - OBJECTIVE: Acute spontaneous bullous urticaria is an extremely rare entity, and
there are few reports with blister formation in acute urticaria patients.
CLINICAL PRESENTATION AND INTERVENTION: We present a 2-year-old girl who was
admitted for bullous spontaneous acute urticaria; the underlying reason for this
was not detected. Nikolsky's sign and Darier's sign were negative. Lesions were
not compatible with erythema multiforme. However, biopsy was not allowed to be
performed. Because of this, the underlying pathogenesis could not be clarified.
The patient recovered by a short course of antihistamine and systemic steroid
treatment, and the lesions did not recur during a 2-year follow-up. CONCLUSION:
Short-term systemic steroid in addition to oral antihistamines resulted in prompt
recovery in a patient with acute urticaria complicated by bullae.
PMID- 29953981
TI - Caffeine Consumption in First-Degree Relatives of Essential Tremor Cases:
Evidence of Dietary Modification Before Disease Onset.
AB - BACKGROUND: Caffeine can exacerbate tremor. Reducing caffeine intake or switching
to decaffeinated beverages can lessen tremor. Unaffected relatives of essential
tremor (ET) cases often have mild, subclinical tremor. One question is whether
the coffee and tea consumption pattern in these individuals differs from that of
controls (Co). METHODS: We ascertained the patterns of coffee and tea intake
using a structured questionnaire, and compared the use in unaffected first-degree
relatives of ET cases (FD-ET) to the use in age-matched Co. Three measures of
relative caffeinated coffee + tea to decaffeinated coffee + tea were constructed.
Caffeine index 1 = (cups of caffeinated coffee + tea) - (cups of decaffeinated
coffee + tea) consumed on the day of evaluation. Caffeine index 2 = (cups of
caffeinated coffee + tea) - (cups of decaffeinated coffee + tea) consumed in a
typical month. The percentage of coffee and tea that was caffeinated in a typical
month was also calculated. RESULTS: There were 263 individuals (190 FD-ET, 73
Co). Caffeine index 1 in FD-ET was less than 1-half that of Co (p = 0.001).
Caffeine index 2 was similarly lower in FD-ET than Co (p = 0.027). The percentage
of coffee and tea that was caffeinated in a typical month was also significantly
lower in FD-ET than Co (p = 0.018). CONCLUSION: The balance of caffeinated to
decaffeinated beverages is different in FD-ET than Co. These data raise several
intriguing questions. Among these is whether relatives of ET cases modify their
caffeine consumption before disease onset.
PMID- 29953983
TI - Chikungunya Virus Interacts with Heat Shock Cognate 70 Protein to Facilitate Its
Entry into Mosquito Cell Line.
AB - AIM: The study was designed to identify putative Chikungunya virus (CHIKV)
receptor/s on C6/36 cells that facilitate viral entry. METHODS: The virus overlay
protein binding assay (VOPBA) was adopted to identify CHIKV-interacting bands
present in C6/36 cell membrane and identity of the protein was established by
mass spectrometry. The role of this protein as a putative CHIKV receptor on C6/36
cells was confirmed by infection inhibition assay. Cell surface localization of
the identified protein was studied by indirect immunofluorescence assay (IFA) on
nonpermeabilized cells and by flow cytometry. Interaction between this protein
and CHIKV was confirmed by co-immunoprecipation (Co-IP) and Western blotting. The
effect of depletion of the identified protein by quercetin was demonstrated by
infection inhibition assay. RESULTS: A 70-kDa protein was identified as a CHIKV
interacting protein by VOPBA. MALDI-TOF analysis followed by homology search
revealed that this protein could be heat shock cognate 70 (HSC 70). Anti-HSC 70
antibodies blocked CHIKV entry into C6/36 cells in a dose-dependent manner. IFA
and flow cytometry analysis demonstrated HSC 70 localization on C6/36 cell
surface. Co-IP experiments confirmed the interaction between HSC 70 and CHIKV
envelope. Quercetin- and YM-01-treated C6/36 cells exhibited dose-dependent
infection inhibition. CONCLUSION: HSC 70 serves as a putative CHIKV receptor on
C6/36 cells.
PMID- 29953984
TI - Towards an Optimized Use of Ocular Corticosteroids: EURETINA Award Lecture 2017.
AB - Since their discovery, glucocorticoids (GCs) have been extensively used for the
treatment of ocular diseases because of their anti-inflammatory, anti-edematous
and angiostatic properties. Various GCs have been synthetized to optimize their
beneficial anti-inflammatory effects and reduce their effects on sodium
retention, identified as a mineralocorticoid effect, leading to a potency and
specificity grading of the different GCs. However, the side effects, specificity
and potency of GCs are highly tissue specific. Because the eye is a confined
organ, local GC administration can reduce the systemic undesirable and severe
side effects but does not protect from potential local toxicity and side effects,
which are dose-dependent, influenced by the disease stage and by genetic and
epigenetic susceptibility. GCs can potentially induce retinal cell death through
non-classical pathways such as paraptosis and non-caspase-dependent apoptosis
that could be undetectable when using classical toxicology tests. To reduce the
risks of toxicity, therapeutic lower doses of GCs are desirable and can be
achieved using optimized methods of administration such as transscleral
iontophoresis or polymeric implants. In the retina, glucocorticoid receptor (GR)
and mineralocorticoid receptor (MR) expression is regulated by disease conditions
such as ocular inflammation. Activation of the MR pathway by its specific ligand,
aldosterone, or by illicit GC occupation can cause retinal edema, subretinal
fluid accumulation, and choroidal vasodilation and leakage, suggesting that
central serous chorioretinopathy could benefit from MR antagonist. A better
understanding of the MR/GR balance in the ocular tissue and the differential
effects of their activation in the different ocular cells is still required to
envisage an optimized use of GCs for the treatment of different ocular disease
conditions.
PMID- 29953985
TI - Effective Desensitization to Tocilizumab in Delayed Hypersensitivity Reaction.
AB - We present tocilizumab desensitization of a 47-year-old woman affected by
rheumatoid arthritis with full body delayed erythematous urticarial reaction.
Skin test for tocilizumab gave cutaneous reaction after 6 h at 20 mg/mL. The
schedule of desensitization was then adapted for non-immediate reaction. We
prepared a desensitization procedure reaching the cumulative dose of 516 mg in 5
weeks. After 6 months, the repetition of skin tests had a negative result, with
demonstration of tolerance induction. Today the patient has good control of the
disease.
PMID- 29953986
TI - Efficacy of End-Tidal Capnography Monitoring during Flexible Bronchoscopy in
Nonintubated Patients under Sedation: A Randomized Controlled Study.
AB - BACKGROUND: Although appropriate sedation is recommended during flexible
bronchoscopy (FB), patients are at risk for hypoventilation due to inadvertent
oversedation. End-tidal capnography is expected as an additional useful monitor
for these patients during FB. OBJECTIVES: The aim of this study was to evaluate
the benefit of additional end-tidal capnography monitoring in reducing the
incidence of hypoxemia during FB in patients under sedation. METHODS: Patients
undergoing FB under moderate sedation without tracheal intubation were randomly
assigned to receive standard monitoring including pulse oximetry or additional
capnography monitoring. Bronchoscopy examiners for the only capnography group
were informed of apnea events by alarms and display of the capnography monitor.
RESULTS: A total of 185 patients were enrolled. Patient characteristics were well
balanced between the two groups. Hypoxemia (at least one episode of pulse
oximeter oxygen saturation [SpO2] < 90%) was observed in 27 out of 94 patients in
the capnography group (29%) and in 42 out of 91 patients in the control group
(46%; p = 0.014), resulting in an absolute risk difference of -17.4% (95%
confidence interval, -31.1 to -3.7). In the capnography group, hypoxemia duration
was shorter (20.4 vs. 41.7 s, p = 0.029), severe hypoxemic events (SpO2 < 85%)
were observed less frequently (16 [17%] vs. 29 [32%], p = 0.019), and the mean
lowest SpO2 value was higher (90.5 vs. 87.6%, p = 0.002). CONCLUSION: End-tidal
capnography monitoring can reduce the incidence and duration of hypoxemia during
FB in nonintubated patients under sedation.
PMID- 29953987
TI - 17-(Allylamino)-17-Demethoxygeldanamycin Enhances Etoposide-Induced Cytotoxicity
via the Downregulation of Xeroderma Pigmentosum Complementation Group C
Expression in Human Lung Squamous Cell Carcinoma Cells.
AB - Etoposide (VP16) is a topoisomerase II inhibitor and has been used for the
treatment of non-small cell lung cancer (NSCLC). Xeroderma pigmentosum
complementation group C (XPC) protein is a DNA damage recognition factor in
nucleotide excision repair and involved in regulating NSCLC cell proliferation
and viability. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone
that is responsible for the stabilization and maturation of many oncogenic
proteins. In this study, we report whether Hsp90 inhibitor 17-allylamino-17
demethoxygeldanamycin (17-AAG) enhanced etoposide-induced cytotoxicity in NSCLC
cells through modulating the XPC expression. We found that etoposide increased
XPC expression in an AKT activation manner in 2 squamous cell carcinoma H1703 and
H520 cells. Knockdown of XPC using siRNA or inactivation of AKT by
pharmacological inhibitor PI3K inhibitor (LY294002) enhanced the cytotoxic
effects of etoposide. In contrast, enforced expression of XPC cDNA or AKT-CA (a
constitutively active form of AKT) reduced the cytotoxicity and cell growth
inhibition of etoposide. Hsp90 inhibitor 17-AAG enhanced cytotoxicity and cell
growth inhibition of etoposide in NSCLC cells, which were associated with the
downregulation of XPC expression and inactivation of AKT. Our findings suggested
that the Hsp90 inhibition induced XPC downregulation involved in enhancing the
etoposide-induced cytotoxicity in H1703 and H520 cells.
PMID- 29953988
TI - Schisantherin A Attenuates Neuroinflammation in Activated Microglia: Role of Nrf2
Activation Through ERK Phosphorylation.
AB - BACKGROUND/AIMS: In the present study, we investigated whether schisantherin A
(StA) had anti-inflammatory effects under neuroinflammatory conditions. METHODS:
The effects of StA and its underlying mechanisms were examined in
lipopolysaccharide (LPS)-activated BV-2 microglial cells by ELISA, qPCR, EMSA,
Western blot, and IHC. RESULTS: Firstly, we found that StA inhibited the
inflammatory response in LPS-activated BV-2 microglia. Secondly, we found that
StA suppressed LPS-induced activation of NF-kappaB via interfering with
degradation of IkappaB and phosphorylation of IkappaB, IKK, PI3K/Akt, JNK, and
p38 MAPK. Thirdly, StA conferred indirect antioxidative effects via quenching ROS
and promoted expression of antioxidant enzymes, including HO-1 and NQO-1, via
stimulating activation of Nrf2 pathways. Finally, we demonstrated that anti
neuroinflammatory actions of StA were dependent on ERK phosphorylation-mediated
Nrf2 activation. CONCLUSION: StA induced ERK phosphorylation-mediated Nrf2
activation, which contributed to its anti-inflammation and anti-oxidation. The
anti-neuroinflammatory and anti-oxidative effects of StA may show preventive
therapeutic potential for various neuroinflammatory disorders.
PMID- 29953990
TI - The Role of Endobronchial Treatment for Bronchial Carcinoid: Considerations from
the Thoracic Surgeon's Point of View.
PMID- 29953989
TI - Regional Subclinical Cerebrovascular Disease Is Associated with Balance in an
Elderly Multi-Ethnic Population.
AB - INTRODUCTION: White matter hyperintensity volume (WMHV) and subclinical brain
infarcts (SBI) are associated with impaired mobility, but less is known about the
association of WMHV in specific brain regions. We hypothesized that anterior WMHV
would be associated with lower scores on the Short Physical Performance Battery
(SPPB), a well-validated mobility scale. METHODS: The SPPB was measured a median
of 5 years after enrollment into the Northern Manhattan MRI sub study. Volumetric
distributions for WMHV in 14 brain regions as a proportion of total cranial
volume were determined. Multi-variable linear regression was performed to examine
the association of SBI and regional log-WMHV with the SPPB score. RESULTS: Among
668 participants with SPPB measurements (mean 74 +/- 9 years, 37% male and 70%
Hispanic), the mean SPPB score was 8.2 +/- 2.9. Total (beta = -0.3 per SD, p =
0.001), anterior periventricular (beta = -0.4 per SD, p = 0.001), parietal (beta
= -0.2 per SD, p = 0.02) and frontal (beta = -0.3 per SD, p = 0.002) WMHVs were
associated with SPPB; other WMHV and SBI were not associated with the SPPB.
CONCLUSIONS: WMHV, especially in the anterior -cerebral regions, is associated
with a lower SPPB. Prevention of subclinical cerebrovascular disease is a
potential target to prevent physical decline in the elderly.
PMID- 29953991
TI - Breast Cancer in a Lagos Facility: Implications for the Institution of a Cancer
Screening Programme.
AB - OBJECTIVE: There are significant epidemiological and biological differences
between breast cancer in blacks and whites which have wide-reaching implications
for the institution of an effective cancer screening programme in Nigeria. The
aim of this study was to describe the clinicopathologic features of breast cancer
diagnosed in our facility and to discuss their implications for cancer screening.
METHODS: A retrospective review of the forms, slides, and results of breast
cancer cases received in our facility over an 8-year period was carried out, as
well as a systematic review of the characteristics of breast cancer in Nigeria,
Africa, the US, and the UK. RESULT: A total of 832 cancers were seen with a mean
age of 49 years. Most cases (97%) were invasive ductal carcinomas not otherwise
specified, high grade (41.9%), and unassociated with ductal carcinoma in situ
(52.3%). Triple-negative tumors were the commonest immunohistochemical type seen
(42.1%), and these were less likely to have an intraductal component (p =
0.0048). Luminal-type tumours were more likely to be low grade (p = 0.0005). The
majority of cases presented in advanced stages with no statistically significant
difference among the different immunohistochemical subtypes (p = 0.7949).
CONCLUSION: The significant epidemiological and biological differences between
breast cancer in Lagos and in western populations are important for the
establishment of an effective breast cancer screening programme uniquely tailored
for the Nigerian population.
PMID- 29953992
TI - Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease.
AB - Systemic endemic mycoses cause high rates of morbidity and mortality in certain
regions of the world and the real impact on global health is not well understood.
Diagnosis and management remain challenging, especially in low-prevalence
settings, where disease awareness is lacking. The main challenges include the
variability of clinical presentation, the fastidious and slow-growing nature of
the fungal pathogens, the paucity of diagnostic tests, and the lack of options
and toxicity of antifungal drugs. Coccidioidomycosis and paracoccidioidomycosis
are restricted to the Americas only, and while histoplasmosis and blastomycosis
also occur predominantly in the Americas, these mycoses have also been reported
on other continents, especially in sub-Saharan Africa. Talaromycosis is endemic
in tropical and subtropical regions in South-East Asia and southern China.
Systemic endemic mycoses causing pulmonary disease are usually acquired via the
airborne route by inhalation of fungal spores. Infections can range from
asymptomatic or mild with flu-like illnesses to severe pulmonary or disseminated
diseases. Skin involvement is frequent in patients with paracoccidioidomycosis,
blastomycosis, sporotrichosis, and talaromycosis and manifests as localized
lesions or diffuse nodules in disseminated disease, but can also occur with other
endemic mycoses. Culture and/or characteristic histopathology from clinical
samples is the diagnostic standard for endemic mycoses. Immunological assays are
often not available for the diagnosis of most endemic mycoses and molecular
amplification methods for the detection of fungal nucleic acids are not
standardized at present. The first-line treatment for mild to moderate
histoplasmosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, and
talaromycosis is itraconazole. Severe illness is treated with amphotericin B.
Patients with severe coccidioidomycosis should receive fluconazole. Treatment
duration depends on the specific endemic mycosis, the severity of disease, and
the immune status of the patient, ranging between 6 weeks and lifelong treatment.
PMID- 29953993
TI - Effects of Folpet, Captan, and Captafol on Human Aromatase in JEG-3 Cells.
AB - BACKGROUND: Estradiol, produced by aromatase (CYP19A1), is very important for
reproduction. Folpet, captan, and captafol belong to the phthalimide class of
fungicides. They are used to protect the leaves of plants or fruits. They could
be endocrine disruptors and may disrupt CYP19A1 activity. METHODS: In the present
study, we investigated the effects of folpet, captan, and captafol on estradiol
production and human CYP19A1 activity in JEG-3 cells. RESULTS: Folpet, captan,
and captafol decreased estradiol production in JEG-3 cells in a concentration
dependent manner. Folpet, captan, and captafol inhibited human CYP19A1 with
inhibitory concentration (IC50) values of 3.55, 10.68, and 1.14 MUmol/L
respectively. These chemicals competitively inhibited human CYP19A1. Molecular
docking simulation analysis showed that they tended to bind to the steroid
binding pocket of the CYP19A1. However, the required concentrations may not be
relevant to the negligible systemic exposures in humans to these chemicals.
CONCLUSION: Folpet, captan, and captafol are potential inhibitors of human
CYP19A1.
PMID- 29953994
TI - Diagnostic Ability and Discriminant Values of OCT-Angiography Parameters in Early
Glaucoma Diagnosis.
AB - PURPOSE: To evaluate papillary, peripapillary, and macular vasculature with
optical coherence tomography angiography in preperimetric (PPG), primary open
angle glaucoma (POAG), and normal eyes, and to assess diagnostic ability and
associations among the vasculature and structural damage. METHODS: This was an
observational, cross-sectional study. Retinal nerve fiber layer (RNFL), ganglion
cell complex thickness, whole-image (wiVD), inside disc (idVD), peripapillary
(ppVD), and macular vessel densities were obtained. Analysis of variance, post
hoc test, and Pearson coefficient were used. The areas under the receiver
operating characteristic curve (AUC) and cut-offs were calculated. RESULTS:
Thirteen healthy, 39 PPG, and 19 POAG eyes were included. Papillary and
peripapillary VD were lower in POAG eyes in all parameters analyzed. wiVD in PPG
eyes (52.37 +/- 5.04%) was significantly decreased compared to healthy eyes
(58.02 +/- 2.02%, p < 0.05). AUC ranged from 0.62 to 0.90; the established cut
off values were 56% for wiVD, 55% for idVD, and 62% for ppVD. Pearson's
correlation coefficient showed a direct correlation between the papillary or
peripapillary VD and RNFL thickness. CONCLUSIONS: Vessel densities in POAG eyes
are significantly lower than in healthy eyes, and they show good discriminatory
abilities. A diminished microvascular network is associated with RNFL thinning
more strongly in POAG than in PPG eyes.
PMID- 29953995
TI - Author's Reply.
PMID- 29953996
TI - Author's Reply.
PMID- 29953998
TI - Adjustable Transobturator Male System after Failed Surgical Devices for Male
Stress Urinary Incontinence: A Feasibility Study.
AB - OBJECTIVES: Feasibility study to evaluate the efficacy and safety of Adjustable
Transobturator Male System (ATOMS) after failed surgical devices for male stress
urinary incontinence (SUI). MATERIALS AND METHODS: Thirty patients were implanted
with ATOMS after they were implanted with surgical device/s previously. SUI
severity was evaluated as dryness (0-1 pad/day), mild (2 pads/day), moderate (3-5
pads/day), or severe (>=6 pads/day). Change in pad-test and pad-count after
adjustment, operative parameters, patient satisfaction, and number and grade of
complications were investigated. RESULTS: Previous failed treatment methods were
artificial urinary sphincter (AUS; n = 19), Advance (n = 10), and Virtue (n = 1).
Six cases had multiple previous treatments. Preoperative SUI was mild 6 (20%),
moderate 11 (36.7%), and severe 13 (43.3%). Median pad-test decreased from 435 mL
baseline to 10 mL after adjustment and pad-count from 4 to 0. Dry-rate was 76.7
and 83.3% declared satisfied. Postoperative SUI distribution was mild in 3 (10%)
and moderate in 4 (13.3%). No patient had urinary retention after catheter
removal. Complications presented in 4 (13.3%; 3 grade-I, 1 grade-II). After a
median of 24 months follow-up, no system experienced infection or urethral
erosion and 1 (3.3%) was removed for inefficacy. CONCLUSION: Based on short-term
efficacy and patient satisfaction, ATOMS can be a realistic alternative for male
SUI after other failed systems, including AUS. The absence of urethral erosion
and limited infective problems makes this alternative attractive for cases with
previous failed treatments.
PMID- 29953999
TI - Inflammation: A Contributor to Depressive Comorbidity in Inflammatory Skin
Disease.
AB - The prevalence of affective disorders such as depression and anxiety is
particularly high in patients with autoimmune diseases, including inflammatory
skin diseases such as psoriasis, atopic dermatitis, and hidradenitis suppurativa.
A dysregulated immune response has been linked to the precipitation of depression
in many patient populations. However, studies examining the extent to which the
underlying skin disease inflammatory processes contribute to depression and a
subsequent decline in quality of life are limited. The published literature over
the past 5 years was reviewed for evidence of a relationship between depression
and inflammatory processes in the context of skin pathology. The findings,
particularly the evidence from interventional clinical trials of targeted anti
cytokine therapies, suggest that pro-inflammatory cytokines associated with
several skin diseases may be causally linked with the coexistent depressive
symptomology.
PMID- 29953997
TI - Bardoxolone Methyl Suppresses Hepatitis B Virus Large Surface Protein Variant W4P
Related Carcinogenesis and Hepatocellular Carcinoma Cell Proliferation Via the
Inhibition of Signal Transducer and Activator of Transcription 3 Signaling.
AB - Bardoxolone methyl (CDDO-me) is a synthetic triterpenoid that has been shown to
suppress various cancers and inflammation. It has been implicated for the
suppression of signal transducer and activator of transcription 3 (STAT3)
mediated signaling, which plays crucial roles in the development and progression
of hepatocellular carcinoma (HCC). Previously, we showed that hepatitis B virus
(HBV) large surface protein (LHB) variant W4P promotes carcinogenesis and tumor
progression through STAT3 activation. Thus, we examined the anti-cancer activity
of CDDO-me against HCC using W4P-LHB-expressing NIH3T3 cells and HepG2 and Huh7
HCC cell lines. CDDO-me exerted cytotoxic activity against W4P-LHB-expressing
NIH3T3 cells, HepG2 cells, and Huh7 cells, and induced apoptotic cell death in a
dose-dependent manner, demonstrating its anti-cancer activity against HCC.
Sublethal concentrations of CDDO-me suppressed STAT3 activation by W4P-LHB
ectopic expression and interleukin-6 treatment in W4P-LHB-NIH3T3 and Huh7 cells
respectively. The suppression of STAT3 activation by CDDO-me in W4P-LHB-NIH3T3
cells was further confirmed by decreased cyclin D1 protein levels and increased
p21 and p53 mRNA synthesis. In addition, CDDO-me treatment resulted in decreased
cell migration and colony formation in in vitro assays using W4P-LHB-NIH3T3,
HepG2, or Huh7 cell lines, supporting its anti-cancer activity through STAT3
inhibition. Furthermore, -CDDO-me administration significantly suppressed tumor
growth induced by W4P-LHB-expressing NIH3T3 cells in nude mice, confirming its
anti-cancer activity. Collectively, our findings demonstrated that CDDO-me is
capable of suppressing STAT3 activation in HCC cells and cells transformed by the
natural variant of HBV protein. The results suggest that CDDO-me can be a
potential therapeutic agent against HCC, especially tumors related to HBV
mutations.
PMID- 29954000
TI - Efficacy and Tolerability of High-Flow Nasal Cannula Oxygen Therapy for Hypoxemic
Respiratory Failure in Patients with Interstitial Lung Disease with Do-Not
Intubate Orders: A Retrospective Single-Center Study.
AB - BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy may provide effective
respiratory management of hypoxemic respiratory failure in patients with
interstitial lung disease (ILD) with a do-not-intubate (DNI) order. OBJECTIVES:
The aim was to assess the efficacy and tolerability of HFNC for these patients.
METHODS: We retrospectively reviewed the records of patients requesting a DNI
order for hypoxemic respiratory failure associated with ILD, comparing treatment
with HFNC and noninvasive positive pressure ventilation (NPPV). Outcomes measured
were 30-day survival, in-hospital mortality, temporary interruption and
discontinuation of the treatment at the patient's request, adverse events, oral
intake, and communication ability at the end of life. RESULTS: A total of 84
patients (HFNC, n = 54; NPPV, n = 30) were analyzed. Neither 30-day survival
(HFNC 31.5% vs. NPPV 30.0%; p = 0.86) nor in-hospital mortality (HFNC 79.6% vs.
NPPV 83.3%; p = 0.78) differed significantly. The temporary interruption and
discontinuation rates were significantly lower in the HFNC group than in the NPPV
group (3.7 vs. 23.3%; p = 0.009 and 0 vs. 10%; p = 0.043, respectively), and that
group had significantly fewer adverse events. Among patients who died in the
hospital, those treated with HFNC had significantly better oral intake and
ability to converse until just before death. CONCLUSION: HFNC had a survival rate
equivalent to that of NPPV and was better tolerated by patients with hypoxemic
respiratory failure associated with ILD who had a DNI order. HFNC allowed
patients to eat and converse until just before death, suggesting that HFNC in
these patients is a reasonable palliative treatment.
PMID- 29954001
TI - Metformin and Colorectal Cancer - A Systematic Review.
AB - OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer-related
deaths. The development of preventive strategies in CRC has been the subject of
much research. Multiple studies have shown an association between diabetes and
CRC. In addition to its glucose-lowering properties, metformin might have an
additional role in the prevention and treatment of CRC. OUR OBJECTIVE: was to
summarize findings on role of metformin in colorectal cancer. METHODS: We
conducted a systematic review of the PubMed and Cochrane databases from January
2005 to December 2017 in search for studies on the association between metformin
and CRC. RESULTS: Of the total of 189 studies identified by the search, we
excluded 123 studies and reviewed the remaining 66 studies on cell lines,
animals, patients with diabetes, and healthy subjects. In vitro and animal
studies have shown a protective effect of metformin use on the incidence of CRC
and amplification of the therapeutic effects of CRC chemotherapy. Studies on
patients with type 2 diabetes treated with metformin analyzed data on total of
146 496 patients. The results of those studies on the role of metformin in CRC
suggest risk reduction and potential applications within therapeutic regimens,
although some of those are conflicting. CONCLUSION: Further studies are warranted
to define the role of metformin in both prevention and treatment of CRC.
PMID- 29954002
TI - [Implementation of the Preventive Health Care Act at the Level of The Federal
States: An Analysis of the Framework Agreements].
AB - BACKGROUND: The implementation of the Preventive Health Care Act 2015 requires
framework agreements between social insurances and ministries on the state level
(Lander). GOALS: This article analyses the 15 agreements already concluded and
provides an overview of similarities and differences between states. METHODS: We
conducted a qualitative content analysis for all 15 agreements. In a first step,
we compared the agreements with the model agreement that had informed the
negotiations in all states, and identified for each paragraph of the agreement
divergent content. In a second step, we compared the divergent content and built
subcategories. Third, we classified similarities and differences of each
category. For this article, we selected 4 categories: goals and fields of action,
committees and regulatory structures, cooperation requirements, cooperation with
further actors. RESULTS: All agreements refer to the nationally agreed health
goals, some define further, state-specific goals. Furthermore, the agreements
provide regulations regarding the goal definition process: some processes only
include the subscribers of the agreement, while others involve all relevant
stakeholders. New regulatory structures are created in almost all states, but
their institutional design and mode of interaction vary highly between state. In
4 states the new structures aim at establishing a dialogue, in 3 states, the goal
is to enable coordination, and in 7 states decision-making bodies are set up.
Almost all agreements are missing concrete commitments regarding cooperation with
other relevant actors on state and local level. CONCLUSION: Most agreements are
very general and their binding character is low. The agreements merely set the
framework that now needs to be filled. Hence, evaluating the actual
implementation of the agreements will only be possible in a few years.
PMID- 29954003
TI - [Balloon dilation oft the Eustachian tube in tympanic membrane retraction].
AB - OBJECTIVE: A tube dysfunction is a common medical issue and can promote chronic
otitis media. With the implementation of the Balloon dilation a treatment of the
chronic tube dysfunction was set. In the present study significance of this
method was assessed, especially questioning the success in practical terms of
tympanic membrane retraction. MATERIAL AND METHODS: In a retrospective study, in
a period of assessment from 2011 until 2016, the data of 81 patients, who
underwent Balloon dilation of the Eustachian tube due to chronic tube dysfunction
with regard to a preoperative presence of tympanic membrane retraction were
evaluated. The success of the Balloon dilation was judged due to the capability
of a postoperative SVT- Test and the patients' self-assessment. With an average
postoperative period of four months, the data of 13 patients were analyzed based
on presence of pre- and postoperative tympanic membrane retraction. RESULTS: The
treatment occurred at all cases without complications. In patients with chronic
tube dysfunction the method revealed an improvement of 46 %, while 31 % of the
patients with tympanic membrane retraction showed an improvement of the middle
ear ventilation. Subjectively perceived 54 % of the patients marked an
improvement of their clinical symptoms. CONCLUSION: In spite of a self-assessed
improvement in 54 % only 31 % of the patients with chronic membrane retraction
showed an objectively measurable success. To evaluate the question if combination
with other middle ear surgeries shows better results, further studies, including
more patients and data, are required.
PMID- 29954004
TI - Jejunal endoscopic submucosal dissection is feasible using the pocket-creation
method and balloon-assisted endoscopy.
PMID- 29954005
TI - Endoscopic submucosal dissection with triangulated traction with clip and rubber
band: the "wallet" strategy.
PMID- 29954006
TI - Endoscopic ultrasound-guided transrectal pelvic abscess drainage using a lumen
apposing metal stent.
PMID- 29954007
TI - Double-balloon platform-assisted rectal endoscopic submucosal dissection.
PMID- 29954008
TI - Reliability and accuracy of a novel classification system using peroral
cholangioscopy for the diagnosis of bile duct lesions.
AB - BACKGROUND: The aim of this study was to propose a novel, comprehensive,
macroscopic classification for bile duct lesions. METHODS: A two-stage protocol
was designed. In Stage I, a retrospective study (September 2013 to September
2015) of patients with bile duct lesions detected by peroral cholangioscopy
(POCS) was performed. A total of 315 images with at least 6 months of follow-up
were recorded, analyzed, and correlated to histology, and were classified as non
neoplastic (one of three types, 1 - 3) or neoplastic (one of four types, 1 - 4)
based on morphological and vascular patterns. In Stage II, a prospective,
nonrandomized, double-blind study was performed from December 2015 to December
2016 to validate the proposed classification. Sensitivity, specificity, positive
and negative predictive values (PPV and NPV, respectively), and positive and
negative likelihood ratios (LR + and LR - , respectively) were calculated (gold
standard: 6-month follow-up). Inter- and intraobserver agreement (kappa value,
kappa) among experts and non-experts were calculated. RESULTS: 171 patients were
included (65 retrospective; 106 prospective). In Stage I, 28/65 cases were
neoplastic and 37 /65 were non-neoplastic, according to the final diagnosis. In
Stage II, 56/106 were neoplastic with a sensitivity, specificity, PPV, NPV, LR +
, and LR - for neoplastic diagnosis of 96.3 %, 92.3 %, 92.9 %, 96 %, 12.52, and
0.04, respectively. The proposed classification presented high reproducibility
among observers, for both neoplastic and subtypes categories. However, it was
better for experts (kappa > 80 %) than non-experts (kappa 64.7 % - 81.9 %).
CONCLUSION: The novel classification system could help physicians to distinguish
non-neoplastic from neoplastic bile duct lesions.
PMID- 29954009
TI - Distally Based Peroneus Brevis Muscle Flap for Large Leg, Ankle, and Foot
Defects: Anatomical Finding and Clinical Application.
AB - BACKGROUND: Peroneus brevis muscle flap is a distinguished, distally based safe
flap that can be manipulated to cover small defects in the leg and ankle. For
large-sized defects, a more distal, larger flap is required either locally or
distantly. METHODS: Forty-two distally based peroneus brevis muscle flaps were
elevated in 42 patients (30 males and 12 females) with major lower leg, ankle,
and proximal foot defects of 6 to 15 cm in length and 6 to 12 cm in width.
Anatomical findings were recorded as number, size, and sources of blood supply,
entry sites, the lowermost two arterial supplies, internal distribution of blood
supply to the muscle, the relationship between external and internal distribution
of the blood vessels, the length of the muscle, the entry site of the main
artery, and the splitting of the proximal portion of the peroneus brevis muscle
to increase its width to sufficiently cover large defects. RESULTS: The
anatomical findings suggested that the muscle can be safely extended to cover a
large defect in the leg, ankle, or proximal foot. In addition, the longitudinal
splitting of the muscle increases its width by up to three times, making it an
excellent long-surviving flap to cover a large defect. CONCLUSION: A distally
based peroneus brevis muscle flap has a rich blood supply and safely reaches the
proximal foot, with a secure splitting to cover large defects in the leg, ankle,
and proximal foot.
PMID- 29954011
TI - Risk of Recurrent Venous Thromboembolism in Autoimmune Diseases: A Systematic
Review of the Literature.
AB - Despite an abundance of literature on the risk of a first venous thromboembolic
event (VTE) in autoimmune diseases, specific recommendations about managing VTE
in autoimmune diseases are lacking. This article aimed to collect evidence on the
risk of recurrent VTE in patients with autoimmune diseases. The authors searched
PubMed/Embase for studies including patients with VTE and autoimmune diseases as
an exposure or studies including patients with autoimmune diseases in which
recurrent VTE was one of the outcomes. Eleven articles were selected from 4,739
unique abstracts. Of the 11 studies, 3 reported time-dependent rates. Two studies
collected rates of recurrence in Behcet's disease, reporting a 5-year recurrence
risk between 35 and 40%. However, the 5-year recurrence risk was lower than 10%
in patients treated with immunosuppressant medication, while two studies
suggested frequent recurrence in patients on only anticoagulant therapy. The
other study reporting time-dependent incidence concerned patients with
inflammatory bowel disease and index VTE. The 5-year risk of recurrent VTE was
33.4%, yielding a hazard ratio of 1.7 versus controls. All studies were
retrospective and therefore risk may overestimate recurrence risk in comparison
with known prospective cohort studies. There are insufficient data to make
confident recommendations about the management of recurrent VTE prevention in
patients with autoimmune diseases in general. The overall VTE risk profile, lower
effectiveness of anticoagulants, and the observation that immunosuppression
lowered risk of recurrence in patients with Behcet's disease seem to warrant
immunosuppressant therapy over anticoagulation as a first consideration when
preventing VTE recurrence in these patients.
PMID- 29954010
TI - High Serum Fractalkine is Associated with Lower Trabecular Bone Score in
Premenopausal Women with Graves' Disease.
AB - Chemokine CX3CL1 (fractalkine) may be an important factor linking thyroid status
and bone remodeling, through tetrac, a derivative of thyroxine. This study
explores the relationship between serum fractalkine levels and parameters of
thyroid status and bone in premenopausal women with Graves' disease (GD) in
comparison to healthy controls. This cross-sectional study included three
premenopausal female groups: active GD; cured GD, and healthy age-, gender-, and
BMI-matched controls. Measurement of serum fractalkine levels (Quantikine(r)
ELISA), total amino-terminal peptide of procollagen type 1 (P1NP), CTx, thyroid
hormones, BMD and trabecular bone score (TBS) were performed in all study
subjects. Sixty women (21, 16, and 23 in active GD, cured GD, and healthy control
groups, respectively) were included. Serum fractalkine levels were higher
(p<0.05) in active and cured GD subjects compared to healthy controls (mean 0.7+/
0.14; 0.93+/-0.15, and 0.48+/-0.13 ng/ml, respectively). Lumbar spine BMD was
lowest in the cured GD group in comparison to active GD and control group
subjects (0.926+/-0.03; 1.016+/-0.03; 1.051+/-0.03 g/cm2; p<0.05, respectively).
TBS was lower (p<0.05) in both GD groups than controls being lowest in those with
active GD (1.395+/-0.02; 1.402+/-0.02, 1.469+/-0.02, respectively). Serum
fractalkine concentration was positively correlated with fT4, and negatively
correlated with TBS values. GD in pre-menopausal females is associated with
increased serum fractalkine concentration and decreased TBS. Fractalkine may be a
currently unappreciated link between hyperthyroidism and bone; further research
into this possibility is needed.
PMID- 29954012
TI - Toxins Are an Excellent Source of Therapeutic Agents against Cardiovascular
Diseases.
AB - Venomous and hematophagous animals use their venom or saliva for survival, to
obtain food, and for self-defense. Venom and saliva from these animals are
cocktails of bioactive molecules primarily composed of proteins and peptides.
These molecules are called toxins because they cause unwanted consequences on
prey. They exhibit unique, diverse, and specific biological activities that
perturb normal physiological processes of their prey and host. However, the
potential of toxins as inspirations for the development of therapeutic agents or
pharmacological tools has also long been recognized. In addition to their small
size, the exquisite selectivity and structural stability of toxins make them
attractive as starting molecule in the development of therapeutic and diagnostic
agents. Drug discovery and development from venomous and hematophagous animals
against cardiovascular diseases have been particularly successful. Some of the
notable success include antihypertensive (captopril and enalapril) and
antiplatelet agents (tirofiban and eptifibatide), as well as anticoagulants
(lepirudin and bivalirudin). Highlighted in this review are many venom or saliva
derived cardiovascular-active proteins and peptides of therapeutic interest,
including those that are currently in preclinical stages and those that have been
approved by FDA and currently in the market. The authors attempt to summarize
their structure, function, mechanism of action, and development with respect to
cardiovascular diseases.
PMID- 29954013
TI - Neurological Sequelae due to Inborn Metabolic Diseases in Pediatric Refugees:
Challenges in Treating the Untreated.
AB - In the 2015 mass migration from Syria and neighboring countries, Germany received
an unprecedented number of 4,76,649 asylum applications. As many of the refugees
arrived in Southern Germany via the Austrian border, the city of Munich was faced
with the majority of Germany's inflow of war refugees and their complex health
issues. Among the refugees were a high number of children. Their main health
issues were infectious diseases and surgical procedures due to trauma, but we
also encountered complex chronic diseases. This report describes clinical
history, signs and symptoms, diagnostics, and treatment of six pediatric patients
with untreated inborn errors of metabolism (IEM): phenylketonuria, biotinidase
deficiency, HMG-CoA lyase deficiency, mucopolysaccharidosis type II, and
mucopolysaccharidosis type VI. Since early diagnosis and treatment is essential
in IEM, both delayed diagnosis and inadequate therapy in refugee children may
lead to significant brain injury, organ damage, and even death. Severe
neurological sequelae in both phenylketonuria and HMG-CoA lyase deficiency could
have been prevented by newborn screening. Screening programs are necessary to
improve the prognoses for refugee children. European Union governments and
involved health care systems should pursue early diagnosis and treatment in
pediatric refugees regarding IEM to prevent neurological long-term sequelae.
PMID- 29954015
TI - ?
PMID- 29954014
TI - Getting to Grips with Cruciate Ligament Disease.
PMID- 29954016
TI - [Delayed neuropsychological sequelae after carbon monoxide poisoning].
AB - Carbon monoxide poisoning is a very common intoxication worldwide. Its clinical
manifestations vary from symptoms like mild headache and dizziness to more
serious issues including death. Less well known are symptoms that occur with a
delay of 2-40 days, such as movement disorders, cognitive impairment or affective
disorders. In this article, we present a case of carbon monoxide poisoning with a
delayed neurological sequela. The following review summarizes the literature on
clinical presentation, diagnostic options, pathophysiology and therapy of this
disease.
PMID- 29954017
TI - [Evaluation of a neuropsychological test battery with psychiatric and
psychosomatic patients].
AB - Neuropsychological assessment should be an integral component of clinical
psychiatric diagnostics. Yet, the commonly used tests have not been investigated
adequately for this population so far. The current study evaluated a clinically
approved neuropsychological test battery by analyzing data on 226 mentally ill
patients using factor and regression analyses. The extraction of three factors
(Speed, Memory, and Executive Functions) proved to be adequate as the tests could
be allocated properly. Regression analysis revealed an economical basis
assessment consisting of three tests (TAP Alertness, VLMT, and Matrices Test).
Based on acceptance, economy, and factorial structure aspects, we recommend the
investigated test battery for neuropsychological assessment of psychiatric and
psychosomatic patients.
PMID- 29954018
TI - [Stress Response in Persons with Alcohol Addiction in the Context of Abstinence
Duration and Disease Severity].
AB - BACKGROUND: Stress increases the risk of developing and maintaining alcohol
addiction. Mechanism for reacting to, and coping with, stress in persons with
alcohol addiction are an important factor enabling them to maintain abstinence in
everyday life. Also of Relevance for abstinence, and in particular craving for
alcohol, is the severity of the dependence. Numerous studies have focused on the
duration of abstinence, but not on the severity of the disease. OBJECTIVE: This
study investigates if, in addition to abstinence duration, also the severity of
the alcohol addiction influences stress responsiveness and ability to cope with
stress. Another objective is to ascertain in which patients such an influence can
be found. The results can shed light on the complex bidirectional relationship
between alcoholism and stress, but are also potentially useful in treating
patients with this disease. METHODS: In a cross-sectional design, 64 alcohol
dependent patients and 30 healthy controls were examined. The alcoholics sample
was divided in two groups according to a duration of abstinence of seven days
and, 70 days. Each group was further divided in a subgroup of individuals with
mild to moderate alcohol addiction and in a subgroup of patients with severe
alcohol addiction (A7-severe and A70-severe). Using the Trierer Social Stress
Test (TSST), all participants were subjected to acute stress. Parameters measured
were salivary cortisol, skin conductance -response, heart rate, addiction-related
variables (addiction severity, duration of alcohol abuse, drinking quantity,
craving, liver enzymes, family history of alcoholism, number of therapies,
smoking), psychopathological variables (anxiety, depression, live events,
personality disorders), acute and long-term stress coping, and level of strain on
everyday life. RESULTS: In patients with severe addiction, the reaction to stress
is weaker and slightly retarded, but also of a longer duration than that patients
with mild and moderate addiction and of healthy controls. This is independent of
the length of abstinence (7 days and 70 days). In severely ill patients,
strategies for coping with acute stress differed from those of the other groups
in that they consisted in stronger flight and avoidance responses, a stronger
need for social support, and a more intense mental preoccupation. Increased
levels of social tension, lack of social recognition, and isolation indicated
chronic stress. Patients with severe alcohol addiction also showed a more
pronounced familial predisposition, stronger craving, increased anxiety, a longer
history of alcohol abuse, and a higher frequency of incisive life events than
patients with mild to moderate alcohol addiction. CONCLUSIONS: The results
indicate that a more differentiated evaluation of stress responsiveness and
stress coping in persons with an alcohol addiction not only length of abstinence,
but also severity of disease have to be taken into account. Further research is
necessary to adjust treatment accordingly.
PMID- 29954019
TI - [Cervical Dystonia].
PMID- 29954020
TI - [Expert Meeting: Integrated Care of the COPD Patients].
AB - Despite considerable progress concerning pharmaceutical therapeutic options, many
COPD patients show a markedly reduced quality of life and increased mortality
risk. This workshop aimed to identify COPD-specific factors impeding an improved
mode of care for patients with COPD. Such factors are: the generally lower social
and educational status of the majority of COPD patients; the stigma of COPD as a
self-inflicted disease ("smoker's lung"); the strict sectoral separation within
the German health care system. In the second part the workshop tried to identify
ways to improve the care of COPD patients. Use of health information technology,
improved communication between care givers and patients as well as between the
health care sectors, integrating rehabilitation and establishing self-management
education are factors within an integrated patient-centered approach. In summary,
an integrated management of the individual patient with COPD including multi
professional teams should contribute to optimizing the quality of COPD care.
PMID- 29954021
TI - Platelet-Rich Plasma for the Treatment of Androgenic Alopecia: A Systematic
Review.
AB - The use of platelet-rich plasma (PRP) has become increasingly commonplace in
facial plastic surgery for the treatment of androgenic alopecia (AGA). However,
this treatment remains novel with a range of application techniques and outcomes
described in the literature. Herein, the authors systematically review the
existing literature on the use and efficacy of PRP for AGA. Systematic review of
PubMed, Embase, and Cochrane databases was performed. Case reports were excluded.
Twenty-four papers met inclusion criteria for this study: 8 randomized control
trials and 16 prospective cohort studies. Twenty-one studies used clinical
criteria to diagnose AGA, while three used confirmatory biopsies. PRP was
injected with or without the use of a numbing agent, and most studies performed
multiple injections (three or more separated by several weeks). Twenty-one
studies reported positive outcomes by objective criteria (88%), while three
suggested that there was no clinical improvement, although in two of these
studies patients still reported increased satisfaction. There were no
complications reported other than transient edema/erythema and pain/headache
associated with the procedure. The existing literature suggests that PRP is a low
risk intervention to treat AGA associated with good patient satisfaction and
objective improvements in outcomes. Further research is needed to optimize
preparation and delivery methods as well as standardize measurements of clinical
outcomes.
PMID- 29954022
TI - Direct Excision of the Lower Eyelid: A Safe and Effective Method for Treating
Dermatochalasis and Pigmentation.
AB - The subciliary and skin pinch approaches are the most widely accepted techniques
for treating dermatochalasis of the lower eyelid. Direct excision (DE) is an
accepted method for treating festoons; however, it is not a popular technique for
the treatment of dermatochalasis and pigment of the lower lid. DE of the lower
lid offers a safe and excellent aesthetic result for dermatochalasis and pigment
of the lower lid, without causing lower lid malposition, which can occur with
more traditional methods. In addition to being able to remove significantly more
skin without risking lower lid malposition, this procedure allows for removal of
the most pigmented and poorly textured skin overlying the nasojugal groove. It is
an effective alternative to the conventional subciliary and skin pinch
approaches.
PMID- 29954023
TI - Economic Analysis of Using Free Fat Graft or Acellular Dermis to Prevent Post
parotidectomy Frey Syndrome.
AB - A decision tree was constructed to determine the incremental cost-effectiveness
ratio (ICER) of grafting techniques used to prevent Frey Syndrome. The authors
performed a sensitivity analysis to calculate what the probability of preventing
Frey Syndrome would have to be and maximum costs associated with using grafting
techniques to warrant their use as more "cost-effective" choice than using
neither. Decision pathways utilized were uses of (1) free fat graft (FFG), (2)
acellular dermis, and (3) no grafting. The probability of developing Frey
syndrome and costs were extracted from previous studies to construct the decision
tree. The primary effectiveness was the ICER of FFG or acellular dermis to
prevent Frey syndrome. The initial outcomes included preventing Frey syndrome
(effectiveness = 1) or developing Frey syndrome (effectiveness = 0). Compared
with not using a graft, the ICER of using FFG and acellular dermis were $10,628
and $50,813, respectively. Frey syndrome was found in 2.6% of patients
postoperatively in FFG group, 9.8% of patients in acellular dermis group, and
30.7% of patients who did not have a graft. The ICER shows absolute dominance of
FFG with lower cost and high effectiveness over acellular dermis. This economic
evaluation strongly supports the use of FFG over acellular dermis as cost
effective approach for prevention of postparotidectomy Frey syndrome.
PMID- 29954024
TI - Intraoperative Mapping of the Subfascial Plexus Using the Transillumination
Method for Head and Neck Reconstruction with Free Style Anterolateral Thigh
Flaps.
AB - Without well recognizing the vascular territories of the perforator, surgery
might damage the pedicle and diminish flap survival. This study described a
transillumination method for intraoperative mapping of the subfascial plexus of
the perforator in the head and neck reconstruction with an anterolateral thigh
(ALT) flap and also compared the perioperative outcomes and complications of the
method with those of the conventional two-pedicle ALT flap. Between January 2011
and December 2017, 26 patients who underwent head and neck reconstruction with
ALT flaps were evaluated as follows: 13 underwent the transillumination method
(case group), and 13 (age- and sex-matched) underwent standard two-pedicle flap
procedures (control group). Demographic factors, diagnosis, flap size, recipient
site, perioperative data, and postoperative complications were compared between
the two groups. There was no significant difference in age, sex, diagnosis,
recipient sites, and flap size between the case and control groups. Regarding the
perioperative outcomes, the harvesting time was significantly shorter in the case
group than in the control group (60 vs. 100 minutes, p < 0.001). The operative
time was shorter in the case group than in the control group, but this difference
was not statistically significant (300 vs. 420 minutes, p = 0.058). The
transillumination method can allow plastic surgeons to easily identify the
perforator vascular plexus of the ALT flap, which facilitates intraoperative flap
design in head and neck reconstruction.
PMID- 29954025
TI - A New Hybrid Technique for Performing a Safer Bilateral Sagittal Split Osteotomy:
Combining Reciprocating Saw and Piezoelectric Devices.
AB - The sagittal split osteotomy (SSO) is an indispensable tool in the correction of
dentofacial abnormalities. In elective orthognathic surgery, it is important that
surgeons inform patients about the risk of complications related to inferior
alveolar nerve damage and unfavorable split. The purpose of this article is to
describe a novel, hybrid technique to SSO by combining a reciprocating saw and
piezoelectric devices with several advantages over traditional "pure" methods
(osteotomies performed by reciprocating saw or piezoelectric devices only) in
terms of precision, rapidity, easier splitting, and decreased complications
related to inferior alveolar nerve damage and bad split with reduced overall
morbidity. The level of evidence was Level IV, therapeutic study.
PMID- 29954026
TI - Four New 2-(2-Phenylethyl)-4H-chromen-4-one Derivatives from the Resinous Wood of
Aquilaria sinensis and Their Inhibitory Activities on Neutrophil Pro-Inflammatory
Responses.
AB - Four new 2-(2-phenylethyl)-4H-chromen-4-one derivatives, 6-hydroxy-5-methoxy-2-[2
(4'-methoxyphenyl)ethyl]chromone (1: ), 6,7-dimethoxy-2-[2-(2'
hydroxyphenyl)ethyl]chromone (2: ), 5-hydroxy-6-methoxy-2-[2-(3'
methoxyphenyl)ethyl]-chromone (3: ), and 7-chloro-8-hydroxy-2-[2-(4'
methoxyphenyl)ethyl]chromone (4: ), have been isolated from the resinous wood of
Aquilaria sinensis, together with 16 known compounds (5: -20: ). Among these, 7
methoxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (5: ) was isolated from a natural
source for the first time. The structures of the new compounds were established
by spectroscopic analyses (1D and 2D NMR, HR-ESI-MS, IR, UV). Nine compounds,
including 1: showed more than 80% inhibition of superoxide anion generation by
human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine at
50 uM.
PMID- 29954027
TI - Fusarihexins A and B: Novel Cyclic Hexadepsipeptides from the Mangrove Endophytic
Fungus Fusarium sp. R5 with Antifungal Activities.
AB - Two novel cyclic hexadepsipeptides, fusarihexin A (1: ) and fusarihexin B (2: ),
and two known compounds, cyclo-(L-Leu-L-Leu-D-Leu-L-Leu-L-Val) (3: ) and cyclo-(L
Leu-L-Leu-D-Leu-L-Leu-L-Ile) (4: ), were isolated from the marine mangrove
endophytic fungus Fusarium sp. R5. Their chemical structures were elucidated on
the basis of spectroscopic data and Marfey's analysis. In an in vitro bioassay,
fusarihexin A (1: ) remarkably inhibited three plant pathogenic fungi:
Colletotrichum gloeosporioides (Penz.) Sacc., which causes anthracnose in many
fruits and vegetables, Colletotrichum musae (Berk. and M. A. Curtis) Arx, which
causes crown rot and anthracnose in bananas, and Fusarium oxysporum Schlecht. f.
sp. lycopersici (Sacc.) W. C. Snyder et H. N. Hansen, which causes Fusarium wilt
and fruit rot in tomatoes. Fusarihexin B (2: ) strongly inhibited C.
gloeosporioides and C. musae. The compounds were more potent than carbendazim,
which is widely used as an agricultural and horticultural fungicide worldwide.
PMID- 29954028
TI - Postural Adjustments Following ACL Rupture and Reconstruction: A Longitudinal
Study.
AB - Longitudinal changes in compensatory and anticipatory postural adjustments around
the knee were investigated from rupture of ACL until return to play after
reconstruction. Twelve ACL-injured participants (ACL-P) were asked to respond to
unpredictable and predictable perturbations before (T1), 2 (T2) and 6 months
after (T3) reconstruction. Twelve healthy participants served as controls.
Compensatory and anticipatory latencies of vastus lateralis (VL) and medialis
(VM) were measured with respect to the arrival of perturbations. ACL-P showed
delayed compensatory latencies compared to controls at T1 for VL (101+/-32 ms vs
63+/-7 ms) and VM (117+/-36 ms vs 75+/-17 ms) and at T2 for VL (94+/-20 ms vs
63+/-7 ms) and VM (94+/-27 ms vs 71+/-11 ms). ACL-P showed earlier anticipatory
latencies than controls for VL at T1 (-69+/-44 ms vs -12+/-12 ms) and T2 (-46+/
17 ms vs -16+/-12 ms). At T3, ACL-P showed delayed compensatory latencies for VL
(91+/-18 ms vs 56+/-21 ms) and VM (95+/-13 ms vs 66+/-4 ms), whilst anticipatory
latencies were restored. Rehabilitation should address delayed compensatory
responses.
PMID- 29954029
TI - High-Definition Video Recording: Taking Sport Technology to the Operating Room.
AB - Filming surgeries for teaching purposes, publications, and patient records has
become increasingly popular as the systems for digital recording have evolved,
becoming high-quality systems, both smaller and lighter. Digital recording allows
long-term storage, retrieval, and database organization. In addition, sharing
digital contents has also become easier since video sharing sites and social
networks make it possible to upload these contents onto the Internet. We describe
a simple and economical system for surgeons to record surgeries in high
definition under sterile conditions without any interference with the surgeon's
line of vision.
PMID- 29954030
TI - Comparison of Transthoracic Device Closure and Surgical Repair with Right
Submammary or Right Infra-axillary Thoracotomy for Perimembranous VSD.
AB - BACKGROUND: Transthoracic device closure (TTDC) and surgical repair with right
infra-axillary thoracotomy (SRRIAT) or with right submammary thoracotomy (SRSMT)
are all the primary alternative treatments for restrictive perimembranous
ventricular septal defect (pmVSD). However, few studies have compared them in
terms of effectiveness and complications. METHODS: Patients with restrictive
pmVSD undergoing TTDC, or SRRIAT, or SRSMT from March 2016 to February 2017 were
retrospectively reviewed in our cardiac center. There were no differences in age
(1.3 +/- 1.2 vs 1.1 +/- 1.1 vs 1.2 +/- 1.1 years), gender (35/37 vs 30/33 vs
29/29), body weight (8.3 +/- 2.6 vs 8.2 +/- 2.4 vs 8.1 +/- 2.5 kg), and size of
VSD (4.2 +/- 1.1 vs 5.2 +/- 1.3 vs 5.1 +/- 1.2 mm) distribution between the three
groups. RESULTS: The procedure success rates were similar in the three groups.
The TTDC group had the shortest operative time, postoperative mechanical
ventilation time, duration of intensive care, postoperative length of hospital
stay, medical cost, and length of the incision. There were no significant
differences in terms of operative time, aortic cross-clamping time, duration of
cardiopulmonary bypass (CPB), blood transfusion volume, mechanical ventilation
time, duration of intensive care, duration of hospital stays, pleural fluid
drainage, or cost between the SRSMT and SRRIAT groups. No significant differences
were noted in terms of major adverse events. CONCLUSIONS: TTDC, SRRIAT, and
SRSMT all showed excellent outcomes and cosmetic appearances for selected VSD
patients. TTDC had advantages over SRRIAT and SRSMT in terms of short operation
duration and smaller incision size and shorter durations of intensive care and
hospital stays.
PMID- 29954031
TI - Using the Hand-Sewn Purse-String Stapled Anastomotic Technique for Minimally
Invasive Ivor Lewis Esophagectomy.
AB - BACKGROUND: Minimally invasive Ivor Lewis esophagectomy (MIILE) is increasingly
being used in the treatment of middle or lower esophageal cancer. Hand-sewn purse
string stapled anastomosis is a classic approach in open esophagectomy. However,
this procedure is technically difficult under thoracoscopy. The hardest part is
delivering the anvil into the esophageal stump. Herein, we report an approach to
performing this step under thoracoscopy. METHODS: A total of 257 consecutive
patients who underwent MIILE between April 2013 and July 2017 were analyzed
retrospectively. The operator hand sewed the purse string using silk thread under
thoracoscopy, and the 25-mm circular stapler was passed through the anterior
axillary line at the fourth intercostal space to finish the side-to-end
gastroesophageal anastomosis. Patient demographics, intraoperative data,
postoperative complications were evaluated. RESULTS: The mean operative time,
thoracoscopy time, and anvil fixation time was 307.0 +/- 34.3, 155.4 +/- 21.5,
and 7.1 +/- 1.6 minute, respectively. The anastomotic leak and anastomotic
stricture occurred in 6.6% (17 of 257) and 3.9% (10 of 257) of patients,
respectively. There was no intraoperative death; one case was death of acute
respiratory distress syndrome (ARDS) for conduit gastric leakage on the 21st
postoperative day. CONCLUSION: Using the hand-sewn purse-string stapled
anastomotic technique for MIILE is feasible and relatively safe in patients with
middle or lower esophageal cancer.
PMID- 29954032
TI - Comparison of Scientific Publications from Three Different Clinical Disciplines
of German Universities.
AB - BACKGROUND: Scientific publications are important for the advancement in
medicine. Surgical disciplines including cardiac surgery are frequently
considered not scientifically leading. However, a specific comparison between
surgical and nonsurgical disciplines has not yet been performed. We thus compared
scientific output of German departments of cardiac surgery with nonsurgical
cardiology departments and surgical departments not addressing the heart (general
surgery) of 34 universities in Germany. METHODS: For each university, the
personnel working at the different departments were identified on the internet
homepage in 2014. We searched for publications of these persons in 2011 to 2013
on PubMed, identified author position, coauthors, and type of article, as well as
journal impact factor (JIF). RESULTS: There were 931 academic persons in cardiac
surgery, 1,486 in general surgery, and 1,814 in cardiology with 12,096
publications related to these persons on PubMed. Cardiology published most
manuscripts, including manuscripts from research conducted (first author),
initiated (senior author), or both. Cardiac surgery had the least publications
and had fewer authors from other departments or institutions. The average JIF was
higher in cardiology compared with the two surgical disciplines. However,
relating the number of publications to the number of employees in the
departments, the differences were no longer apparent. CONCLUSION: We conclude
that the number of publications in German universities appears to be a function
of the number of academic personnel and not of the discipline. The lower JIFs in
surgery may be due to the smaller surgical fields and/or due to less high impact
interdisciplinary/interinstitutional publications in surgery.
PMID- 29954033
TI - ?
PMID- 29954034
TI - ?
PMID- 29954036
TI - ?
PMID- 29954037
TI - ?
PMID- 29954038
TI - ?
PMID- 29954039
TI - ?
PMID- 29954040
TI - ?
PMID- 29954041
TI - [Refresher Orthogeriatrics].
AB - Fragility fractures are associated with a substantial mortality and morbidity.
Because of the high prevalence of comorbidities and a high risk of complications
the application of geriatric principles in the complex treatment of these
patients is vital. The last years have seen a paradigm shift in the treatment of
fragility fractures from an orthopedic disorder towards an orthogeriatric
syndrome. This article reviews the orthogeriatric principles of treating
fragility fractures.
PMID- 29954042
TI - Traveling There and Back Again: A Fingernail's Tale.
AB - This study focuses on the examination of stable isotope biomarkers in human
fingernails of travelers who ventured away from Salt Lake City, UT and
subsequently returned. Here, we describe three case studies examining: individual
travelers (n = 4), paired travelers (n = 2), and a traveler (n = 1) who
repeatedly left and returned. Our case studies examined the influences of dietary
and drinking water inputs on fingernail stable isotope profiles for
reconstructing travel histories. Stable isotope data were compared with
theoretical and predictive models that laid the groundwork for anthropological
and forensic geospatial reconstruction of travel histories. Drinking water inputs
strongly influenced stable isotope profiles and the patterns observed were
consistent with reported travel histories. Finally, observed fingernail stable
isotope ratio data were consistent with modeled rates of stable isotope turnover
and transition to expected values for the new environment. The results of our
study further support the use of fingernail tissues for travel history
reconstruction.
PMID- 29954043
TI - Storytelling as Adaptive Collective Sensemaking.
AB - Storytelling represents a key element in the creation and propagation of culture.
Three main accounts of the adaptive function of storytelling include (a)
manipulating the behavior of the audience to enhance the fitness of the narrator,
(b) transmitting survival-relevant information while avoiding the costs involved
in the first-hand acquisition of that information, and (c) maintaining social
bonds or group-level cooperation. We assess the substantial evidence collected in
experimental and ethnographic studies for each account. These accounts do not
always appeal to the specific features of storytelling above and beyond language
use in general. We propose that the specific adaptive value of storytelling lies
in making sense of non-routine, uncertain, or novel situations, thereby enabling
the collaborative development of previously acquired skills and knowledge, but
also promoting social cohesion by strengthening intragroup identity and
clarifying intergroup relations.
PMID- 29954044
TI - Potential mechanisms in fear of birth: The role of pain catastrophizing and
intolerance of uncertainty.
AB - BACKGROUND: Although many pregnant women experience fear, worry, or anxiety
relating to the upcoming birth, little is known regarding the psychological
mechanisms contributing to these experiences. In this study, we wanted to take a
first step in trying to identify mechanisms of potential interest. The objective
of this cross-sectional study was thus to investigate pain catastrophizing,
intolerance of uncertainty, positive worry beliefs, and cognitive avoidance as
potential mechanisms predicting fear of birth among pregnant women. METHODS: A
sample of 499 pregnant women, recruited in antenatal health care settings in 2
Swedish regions, completed the Fear of Birth Scale, along with measurements of
the mechanisms of interest. Linear and logistic hierarchical regression analyses
were used to investigate the extent to which pain catastrophizing, intolerance of
uncertainty, positive worry beliefs, and cognitive avoidance predicted fear of
birth, both as a continuous and a dichotomous measure. RESULTS: Logistic
regression analysis showed high levels of pain catastrophizing and intolerance of
uncertainty to be the best predictors of fear of birth, OR 3.49 (95% CI 2.17
5.61) and OR 3.25 (95% CI 2.00-5.27), respectively. Positive beliefs about worry
and cognitive avoidance were both correlated with fear of birth as a continuous
measure, but did not contribute to the logistic regression model. CONCLUSIONS:
Pain catastrophizing and intolerance of uncertainty were the most evident
predictors of fear of birth. Although preliminary, the findings suggest that
interventions targeting catastrophic cognitions and intolerance of uncertainty
might be relevant to psychological treatment for fear, worry, or anxiety relating
to giving birth.
PMID- 29954045
TI - Maternity care experiences and health needs of migrant women from female genital
mutilation-practicing countries in high-income contexts: A systematic review and
meta-synthesis.
AB - BACKGROUND: Female genital mutilation (FGM) is a cultural practice defined as the
partial or total removal of the external female genitalia for nontherapeutic
indications. Due to changing patterns of migration, clinicians in high-income
countries are seeing more women from countries where the practice is prevalent.
This review aims to understand the sociocultural and health needs of these women
and identify opportunities to improve the quality of maternity care for women
with FGM. METHODS: We undertook a systematic review and meta-synthesis of peer
reviewed primary qualitative research to explore the experience and needs of
migrant women with FGM receiving maternity care. A structured search of nine
databases was undertaken, screened papers appraised, and a thematic analysis
undertaken on data extracted from the findings and discussion sections of
included papers. RESULTS: Sixteen peer-reviewed studies were included in the
systematic review. Four major themes were revealed: Living with fear, stigma, and
anxiety; Feelings of vulnerability, distrust, and discrimination; Dealing with
past and present ways of life after resettlement; and Seeking support and
involvement in health care. CONCLUSIONS: The findings suggest that future actions
for improving maternity care quality should be focused on woman-centered
practice, demonstrating cultural safety and developing mutual trust between a
woman and her care providers. Meaningful consultation with women affected by FGM
in high-income settings requires cultural sensitivity and acknowledgment of their
specific circumstances. This can be achieved by engaging women affected by FGM in
service design to provide quality care and ensure woman-focused policy is
developed and implemented.
PMID- 29954046
TI - Beyond serum creatinine: which tools to evaluate renal function in cirrhotic
patients?
AB - In cirrhotic patients, a high serum creatinine value is an independent mortality
factor. Similarly, it is predictive of renal insufficiency after liver
transplantation. In these cases, chronic kidney disease is also an independent
mortality factor. A relevant evaluation of glomerular filtration rate is crucial,
particularly in cases of end-stage liver disease or liver transplantation, and is
key for the decision to undertake dual liver-kidney transplantation. Serum
creatinine or creatinine-based equations are the most used tools in clinical
practice but they significantly overestimate renal function. Equilibrium inulin
renal clearance remains the gold standard but is time consuming and expensive.
Cystatin C and cystatin C-based equations are less influenced by muscle mass or
bilirubin value, but their dosage is not standardized and they are expensive.
Pharmacological models using exogenous markers, new kidney biomarkers, Doppler
coupled with ultrasounds, and kidney histology could be interesting tools but
their indications need to be specified.
PMID- 29954047
TI - Human-Computer Interaction in Face Matching.
AB - Automatic facial recognition is becoming increasingly ubiquitous in security
contexts such as passport control. Currently, Automated Border Crossing (ABC)
systems in the United Kingdom (UK) and the European Union (EU) require
supervision from a human operator who validates correct identity judgments and
overrules incorrect decisions. As the accuracy of this human-computer interaction
remains unknown, this research investigated how human validation is impacted by a
priori face-matching decisions such as those made by automated face recognition
software. Observers matched pairs of faces that were already labeled onscreen as
depicting the same identity or two different identities. The majority of these
labels provided information that was consistent with the stimuli presented, but
some were also inconsistent or provided "unresolved" information. Across three
experiments, accuracy consistently deteriorated on trials that were
inconsistently labeled, indicating that observers' face-matching decisions are
biased by external information such as that provided by ABCs.
PMID- 29954048
TI - Translating the ICAP Theory of Cognitive Engagement Into Practice.
AB - ICAP is a theory of active learning that differentiates students' engagement
based on their behaviors. ICAP postulates that Interactive engagement,
demonstrated by co-generative collaborative behaviors, is superior for learning
to Constructive engagement, indicated by generative behaviors. Both kinds of
engagement exceed the benefits of Active or Passive engagement, marked by
manipulative and attentive behaviors, respectively. This paper discusses a 5-year
project that attempted to translate ICAP into a theory of instruction using five
successive measures: (a) teachers' understanding of ICAP after completing an
online module, (b) their success at designing lesson plans using different ICAP
modes, (c) fidelity of teachers' classroom implementation, (d) modes of students'
enacted behaviors, and (e) students' learning outcomes. Although teachers had
minimal success in designing Constructive and Interactive activities, students
nevertheless learned significantly more in the context of Constructive than
Active activities. We discuss reasons for teachers' overall difficulty in
designing and eliciting Interactive engagement.
PMID- 29954049
TI - "Girls Are as Good as Boys at Math" Implies That Boys Are Probably Better: A
Study of Expressions of Gender Equality.
AB - Although "Girls are as good as boys at math" explicitly expresses equality, we
predict it could nevertheless suggest that boys have more raw talent. In
statements with this subject-complement structure, the item in the complement
position serves as the reference point and is thus considered more typical and
prominent. This explains why "Tents are like houses," for instance, sounds better
than "Houses are like tents"-people generally think of houses as more typical.
For domains about ability, the reference point should be the item that is
typically more skilled. We further propose that the reference point should be
naturally more skilled. In two experiments, we presented adults with summaries of
actual scientific evidence for gender equality in math (Experiment 1) or verbal
ability (Experiment 2), but we manipulated whether the reference point in the
statements of equality in the summaries (e.g., "Boys' verbal ability is as good
as girls'") was girls or boys. As predicted, adults attributed more natural
ability to each gender when it was in the complement rather than subject
position. Yet, in Experiment 3, we found that when explicitly asked, participants
judged that such sentences were not biased in favor of either gender, indicating
that subject-complement statements must be transmitting this bias in a subtle
way. Thus, statements such as "Girls are as good as boys at math" can actually
backfire and perpetuate gender stereotypes about natural ability.
PMID- 29954050
TI - Role of Handheld In Vivo Reflectance Confocal Microscopy for the Diagnosis of
Fabry Disease: A Case Report.
AB - Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the
deficient activity of the lysosomal enzyme α-galactosidase that leads to a
systemic accumulation of globotriaosylceramide. Handheld in vivo reflectance
confocal microscopy (HH-RCM) is a useful modern technique in diagnosis and follow
ups of many skin diseases. This noninvasive device provides high-resolution and
high-contrast real-time images to study both the skin and the ocular surface
structures that can help clinicians to confirm the diagnosis of FD. HH-RCM could
be helpful even for the follow-ups of these patients, enabling us to monitor the
effect of enzyme replacement therapy on corneal cells and keratinocytes.
PMID- 29954051
TI - Lecture 1-Justification of the Value of Clinical Pharmacy Services and Clinical
Indicators Measurements-Introductory Remarks from a Traveler on a 40-Year
Wayfaring Journey with Clinical Pharmacy and Pharmaceutical Care.
AB - Without question, health care delivery, and clinical pharmacy’s purpose in
it, is changing rapidly all over the world. Pharmacy’s place in the new
health care environment is ensured only to the extent that the purpose of
pharmaceutical care is understood and transmitted to the global structures of
these developing organizational patterns and paradigm shifts. While the current
trend toward commodification of illness and treatment seems to be driving efforts
to consolidate the economic factors of pharmaceutical distribution, a new type of
practice—patient-driven health care—has continued to shape the
interactions of pharmacists and patients all over the world. A thorough
understanding of the above factors involved in pharmacy’s history, present,
and future are necessary for clinical practice preparation, as well as for value
justification. How clinical pharmacy will succeed in this kind of social and
economic milieu is precisely why this series of lectures and roundtables will
help us embrace many of the vexing issues that clinical pharmacy administrators
and practitioners face in daily practice.
PMID- 29954052
TI - Characterization of Aroma-Active Compounds in Seed Extract of Black Cumin
(Nigella sativa L.) by Aroma Extract Dilution Analysis.
AB - Turkish Nigella sativa L. seed extracts were used to detect the aroma and key
odorant compounds of the spice using gas chromatography-mass spectrometry
olfactometry (GC-MS-O). Volatile compounds were extracted by the purge and trap
extraction (PTE) method. A total of 32 volatile compounds consisting of different
chemical classes acids (13), alcohols (7), phenols (3), terpene (1), esters (2),
ketones (2), aldehyde (1), lactone (1) and hydrocarbons (2) were determined. The
amounts of volatile compounds were found to be 21,544 µg kg−1. The
application of aroma extract dilution analysis (AEDA) revealed the presence of 13
odor-active compounds alcohols (2), carboxylic acids (4), phenols (2), terpene
(1), ketone (1), hydrocarbon (1) and unknown compounds (2) in Nigella sativa L.
extract. Flavor dilution (FD) factors of key odorants ranged between 4 and 1024,
while odor activity values (OAV) were in the range of 1.0 to 170.8. Acetoin was
the only aroma-active ketone detected in Nigella sativa L. seed extracts. It had
the strongest aroma (FD = 1024) and provided a buttery odor. This compound
represented the most abundant compound of overall aroma profile with a
concentration of 9394 µg kg−1, followed by isobutanoic acid (FD = 512
with a concentration of 218 µg kg−1) and contributed a powerful aroma
and a cheesy characteristic odor.
PMID- 29954053
TI - Delivering Phage Products to Combat Antibiotic Resistance in Developing
Countries: Lessons Learned from the HIV/AIDS Epidemic in Africa.
AB - The antimicrobial resistance (AMR) crisis and HIV/AIDS epidemic exhibit many
parallels. In both, infectious diseases have caused millions of deaths worldwide,
with AMR expected to kill even more people each year than HIV/AIDS did at its
peak. In addition, both have required or will require new classes of drugs for
control. For HIV/AIDS, development of vital antiretroviral drugs (ARVs) was
accomplished in several stages: expanding public awareness about the disease,
gathering commitment from the international community to tackle the problem, and
eventually establishing policies and global funds to deliver new therapeutics.
For AMR, the pursuit of new antimicrobials appears to be following a similar
trajectory. This paper examines how lessons and processes leading to ARVs might
be applied to developing AMR drugs, in particular bacteriophages (phages). These
possess many essential characteristics: inexpensive manufacture, rapid drug
development, and a ready means to prevent phage-resistant microbes from emerging.
However, the broad application of phage-based products has yet to be fully
demonstrated, and will require both international coordination and modified
regulatory policies.
PMID- 29954054
TI - The Importance of External Contacts in Job Performance: A Study in Healthcare
Organizations Using Social Network Analysis.
AB - There is evidence that relations between physicians and nurses within healthcare
institutions might be shaped by informal aspects of such relations and by links
to people external to the organization, with an impact on work performance.
Social network analysis is underutilized in exploring such associations. The
paper aims to describe physicians’ and nurses’ relationships outside
their clinical units and to explore what kind of ties are related to job
performance. A network analysis was performed on cross-sectional data. The study
population consisted of 196 healthcare employees working in a public hospital and
a primary healthcare centre in Spain. Relational data were analysed using the
UCINET software package. Measures included: (i) sample characteristics; (ii)
social network variables; and (iii) team performance ratings. Descriptive
statistics (means, medians, percentages) were used to characterize staff and
performance ratings. A correlational analysis was conducted to examine the
strength of relationships between four different types of ties. Our findings
suggest that external ties only contribute to improving the performance of
physicians at both the individual and team level. They are focused on the
decision-making process about the therapeutic plan and, therefore, might need to
seek advice outside the workplace. In contrast, external ties are not relevant
for the work performance of nurses, as they need to find solutions to immediate
problems in a short period of time, having strong ties in the workplace. Social
network analysis can illuminate relations within healthcare organizations and
inform the development of innovative interventions.
PMID- 29954055
TI - Do Socio-Economic Characteristics Affect Travel Behavior? A Comparative Study of
Low-Carbon and Non-Low-Carbon Shopping Travel in Shenyang City, China.
AB - Choices regarding mode of travel have an evident effect on environment pollutants
and public health. This paper makes a significant contribution by examining the
differences between low-carbon and non-low-carbon travel mode choices during
shopping trips, and how socio-economic characteristics impact individual travel
behavior based on data gathered from a questionnaire conducted in Shenyang,
China. The study found that, firstly, low-carbon travel modes were more common
than non-low-carbon travel modes for shopping, and the average travel distance by
non-low-carbon modes was a little longer than that of low-carbon modes. Secondly,
suburban and wholesale specialized commercial centers attracted more residents
travelling longer distances by non-low carbon modes, especially private car,
compared to regional commercial centers in inner city areas. Thirdly, strong
relationships between car ownership, gender, monthly income, and travel mode
choices were identified in a binary logistic regression model. This study thus
highlights the importance of sustainable transportation policies to advocate low
carbon travel modes and reduce carbon emissions.
PMID- 29954056
TI - Obesity with Comorbid Eating Disorders: Associated Health Risks and Treatment
Approaches.
AB - Obesity and eating disorders are each associated with severe physical and mental
health consequences, and individuals with obesity as well as comorbid eating
disorders are at higher risk of these than individuals with either condition
alone. Moreover, obesity can contribute to eating disorder behaviors and vice
versa. Here, we comment on the health complications and treatment options for
individuals with obesity and comorbid eating disorder behaviors. It appears that
in order to improve the healthcare provided to these individuals, there is a need
for greater exchange of experiences and specialized knowledge between healthcare
professionals working in the obesity field with those working in the field of
eating disorders, and vice-versa. Additionally, nutritional and/or behavioral
interventions simultaneously addressing weight management and reduction of eating
disorder behaviors in individuals with obesity and comorbid eating disorders may
be required. Future research investigating the effects of integrated medical,
psychological and nutritional treatment programs addressing weight management and
eating disorder psychopathology in individuals with obesity and comorbid eating
disorder behaviors—such as binge eating—is necessary.
PMID- 29954057
TI - Methadone for Analgesia in Children with Life-Limiting Illness: Experience from a
Tertiary Children's Health Service.
AB - Methadone has the potential to assist in the management of pain in children with
life-limiting illness, but its use is limited by its complex pharmacokinetic
profile and limited research on its use in children. This is a retrospective
review of the use of methadone as an analgesic in 16 children with life-limiting
illness. Efficacy, dosing and side effect profile were analysed. Fifteen (94%)
patients had improvements in their analgesia with minimal observed adverse
effects. Patients were either rapidly converted from a prior opioid in one change
or received methadone as an adjunct medication. Conversions were calculated using
ratios frequently in the range of 10:1 to 20:1 from the oral morphine equivalent
total daily dose (MEDD). Adjunct initial dosing was a low dose trial, often
beginning with 1 mg at night. Only two patients required a dose adjustment due to
side effects attributed to methadone. This was despite the cohort having
significant underlying illnesses, extensive concurrent medications, and high
methadone dosing where needed. Analysis of dosing and ratios indicates that an
individualised approach is required. Based on this and on the infrequency of
methadone use in this population, specialist assistance with dosing is
recommended. Further research, including prospective and pharmacokinetic studies,
is recommended.
PMID- 29954058
TI - Mind-Body Approaches to Prevention and Intervention for Alcohol and Other Drug
Use/Abuse in Young Adults.
AB - Alcohol and other drug (AOD) misuse is highly prevalent among young adults and
creates myriad long-term problematic social, economic, and health consequences.
Current treatments aimed at preventing or alleviating AOD misuse have
demonstrated fairly inconsistent and weak effectiveness and, thus, are far from a
complete solution. In this review, we describe the current state of AOD
interventions for young adults and present an alternative emotion regulation
framework for understanding AOD use/misuse. We then describe implications of this
framework for interventions to promote healthier emotion regulation to
successfully reduce AOD use/misuse. In particular, we assert that mind-body
approaches, such as meditation, distress tolerance, and yoga, may promote emotion
regulation skills that allow young adults to manage their stressful experiences
and distressing emotions without AOD use. We review the available literature on
mind-body interventions targeting AOD use/misuse in young adults and offer
suggestions for future intervention development and research.
PMID- 29954060
TI - Hybrid Metasurface Based Tunable Near-Perfect Absorber and Plasmonic Sensor.
AB - We propose a hybrid metasurface-based perfect absorber which shows the near-unity
absorbance and facilities to work as a refractive index sensor. We have used the
gold mirror to prevent the transmission and used the amorphous silicon (a-Si)
nanodisk arrays on top of the gold mirror which helps to excite the surface
plasmon by scattering light through it at the normal incident. We numerically
investigated the guiding performance. The proposed absorber is polarization
independent and shows a maximum absorption of 99.8% at a 932 nm wavelength in the
air medium. Considering the real applications, by varying the environments
refractive indices from 1.33 to 1.41, the proposed absorber can maintain
absorption at more than 99.7%, with a red shift of the resonant wavelength. Due
to impedance matching of the electric and magnetic dipoles, the proposed absorber
shows near-unity absorbance over the refractive indices range of 1.33 to 1.41,
with a zero-reflectance property at a certain wavelength. This feature could be
utilized as a plasmonic sensor in detecting the refractive index of the
surrounding medium. The proposed plasmonic sensor shows an average sensitivity of
325 nm/RIU and a maximum sensitivity of 350 nm/RIU over the sensing range of 1.33
to 1.41. The proposed metadevice possesses potential applications in solar
photovoltaic and photodetectors, as well as in organic and bio-chemical
detection.
PMID- 29954059
TI - Antiobesity Effects of Ginsenoside Rg1 on 3T3-L1 Preadipocytes and High Fat Diet
Induced Obese Mice Mediated by AMPK.
AB - Ginsenosides Rg1 is one of the major pharmacologically active saponins in
ginseng, which as an antioxidant reduces oxidative damage in the liver and can
also be used to prevent cardiovascular diseases and diabetes. However, there is
no research targeting the effect of lipid metabolism in high-fat diet (HFD)
induced mice. In this study, we evaluated the anti-obesity effects of Rg1 in 3T3
L1 adipocyte cells and HFD-induced obese C57BL/6J mice. Administration of Rg1 to
HFD-induced obese mice significantly decreased body weight, total cholesterol,
and total triglyceride levels. In addition to effects in 3T3-L1 cells, Rg1
reduced the accumulation of lipid droplets in a dose-dependent manner.
Furthermore, Rg1 exhibits an anti-adipogenic effect via regulation of the
expression of the transcriptional factors and lipid metabolism-related genes in
vivo and in vitro. We observed that Rg1 administration significantly increased
the phosphorylation level of AMP-activated protein kinase (AMPK) in both
epididymal white adipose tissue and 3T3-L1 cells. These results indicated that
Rg1 works both in an anti-adipogenic and anti-obesity manner through inducing
AMPK activation, inhibiting lipogenesis, and decreasing intracellular lipid
content, adipocyte size, and adipose weight.
PMID- 29954061
TI - Quartz-Enhanced Photoacoustic Spectroscopy Sensor with a Small-Gap Quartz Tuning
Fork.
AB - A highly sensitive quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor
based on a custom quartz tuning fork (QTF) with a small-gap of 200 μm was
demonstrated. With the help of the finite element modeling (FEM) simulation
software COMSOL, the change tendency of the QEPAS signal under the influence of
the laser beam vertical position and the length of the micro-resonator (mR) were
calculated theoretically. Water vapor (H2O) was selected as the target analyte.
The experimental results agreed well with those of the simulation, which verified
the correctness of the theoretical model. An 11-fold signal enhancement was
achieved with the addition of an mR with an optimal length of 5 mm in comparison
to the bare QTF. Finally, the H2O-QEPAS sensor, which was based on a small-gap
QTF, achieved a minimum detection limit (MDL) of 1.3 ppm, indicating an
improvement of the sensor performance when compared to the standard QTF that has
a gap of 300 μm.
PMID- 29954062
TI - Nano-Pulse Stimulation for the Treatment of Pancreatic Cancer and the Changes in
Immune Profile.
AB - A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor
prognosis. Current standard of care is rarely effective against late-stage
pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a
local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic
cancer model and characterized corresponding changes in the immune profile. A
single NPS treatment either achieved complete tumor regression or prolonged
overall survival in animals with partial tumor regression. While this is very
encouraging, we also explored if this local ablation effect could also result in
immune stimulation, as was observed when NPS led to the induction of immune
mediated protection from a second tumor challenge in orthotopic mouse breast and
rat liver cancer models. In the Pan02 model, there were insufficient abscopal
effects (1/10) and vaccine-like protective effects (1/15) suggesting that NPS
induced immune mechanisms in this model were limited. To evaluate this further,
the immune landscape was analyzed. The numbers of both T regulatory cells (Tregs)
and myeloid derived suppressor cells (MDSCs) in blood were significantly reduced,
but memory (CD44+) T-cells were absent. Furthermore, the numbers of Tregs and
MDSCs did not reduce in spleens compared to tumor-bearing mice. Very few T-cells,
but large numbers of MDSCs were present in the NPS treated tumor microenvironment
(TME). The number of dendritic cells in the TME was increased and multiple
activation markers were upregulated following NPS treatment. Overall, NPS
treatments used here are effective for pancreatic tumor ablation, but require
further optimization for induction of immunity or the need to include effective
combinational NPS therapeutic strategy for pancreatic cancer.
PMID- 29954064
TI - Increasing the Yield of Irish Brown Crab (Cancer pagurus) during Processing
without Adversely Affecting Shelf-Life.
AB - During the processing of Irish Brown Crab (Cancer pagurus), protein and moisture
are released and losses up to 10% (by weight) are common. The objective of this
study was to investigate the use of clean label ingredients to reduce this loss,
without adversely affecting shelf-life or promoting the growth of spoilage
bacteria. Following preliminary studies, 5% (w/v) sodium caseinate (SC) and (5%,
w/v) potato starch (PS), with and without (0.5%, w/v) ascorbic acid (AA) were
selected. Ninety crabs (30 per treatment) were soaked and boiled in water
(control 1), AA (control 2), SC, PS, SC plus AA, or PS plus AA and analyzed for
cook loss as well as pH, aw, water holding capacity (WHC), and microbial shelf
life (total viable count (TVC), total Enterobacteriaceae count (TEC), and
spoilage bacteria) during 28 days storage at 4 °C. On average, 11.1% of the
control 1 weight was lost during processing. This was reduced to 8.0% when
treated with AA (control 2) and to 3.5%, 4.7%, 5.8%, and 2.3% with SC, PS, SC
plus AA, and PS plus AA, respectively. None of these treatments negatively
impacted on shelf-life and similar growth curves were observed for TVC, TEC,
Pseudomonas spp., Clostridium spp., lactic acid bacteria (LAB), and hydrogen
disulphide producing bacteria, regardless of treatment. It was therefore
concluded that, subject to sensory evaluation and validation under commercial
conditions, these natural ingredients could be used to substantially increase the
yield and hence commercial value of crab meat, without adversely affecting shelf
life.
PMID- 29954066
TI - Process Optimization, Characterization and Antioxidant Capacity of Oat (Avena
Sativa L.) Bran Oil Extracted by Subcritical Butane Extraction.
AB - Oat bran is a traditional agricultural byproduct and rarely used in edible oil
processing. In this paper, oat bran oil (OBO) was firstly extracted by
subcritical butane extraction (SBE) and the extraction process was optimized
using response surface methodology. Three variables involving liquid-to-solid
ratio, extraction time and extraction temperature were studied. The optimum
conditions for extraction of OBO were obtained as follows: liquid-to-solid ratio
4.30, extraction time 48.15 min, and extraction temperature 46.52 °C. Based
on this, an alternative method (SBE-e) for cosolvent (ethanol) was proposed to
improve SBE method. Compared to conventional hexane extraction (CHE), the SBE-e
had significant effect on yield, bioactive compounds (phytosterols and phenols)
and antioxidant capacity (AC) in the extracted OBO. The results indicated that
the proposed methods were appropriate for OBO extraction. Additionally, OBO had
the potential to be an acceptable substitute for edible oil, owing to its
desirable physicochemical characteristics, a balanced fatty acids composition and
high antioxidant capacity.
PMID- 29954065
TI - Comparative Transcriptome Analysis Identifies Genes Putatively Involved in 20
Hydroxyecdysone Biosynthesis in Cyanotis arachnoidea.
AB - Cyanotis arachnoidea contains a rich array of phytoecdysteroids, including 20
hydroxyecdysone (20E), which displays important agrochemical, medicinal, and
pharmacological effects. To date, the biosynthetic pathway of 20E, especially the
downstream pathway, remains largely unknown. To identify candidate genes involved
in 20E biosynthesis, the comparative transcriptome of C. arachnoidea leaf and
root was constructed. In total, 86.5 million clean reads were obtained and
assembled into 79,835 unigenes, of which 39,425 unigenes were successfully
annotated. The expression levels of 2427 unigenes were up-regualted in roots with
a higher accumulation of 20E. Further assignments with Kyoto Encyclopedia of
Genes and Genomes (KEGG) pathways identified 49 unigenes referring to the
phytoecdysteroid backbone biosynthesis (including 15 mevalonate pathway genes, 15
non-mevalonate pathway genes, and 19 genes for the biosynthesis from farnesyl
pyrophosphate to cholesterol). Moreover, higher expression levels of mevalonate
pathway genes in roots of C. arachniodea were confirmed by real-time quantitative
PCR. Twenty unigenes encoding CYP450s were identified to be new candidate genes
for the bioreaction from cholesterol to 20E. In addition, 90 transcription
factors highly expressed in the roots and 15,315 unigenes containing 19,158
simple sequence repeats (SSRs) were identified. The transcriptome data of our
study provides a valuable resource for the understanding of 20E biosynthesis in
C. arachnoidea.
PMID- 29954067
TI - Defect Structure and Oxide Ion Conduction of Potassium Ion Substituted CaWO4.
AB - We have prepared Ca1−xKxWO4−x/2 solid solutions with the Scheelite
type structure to investigate high-temperature electrochemical properties. Room
temperature X-ray diffraction suggested the solid solution range was x ≤ 0.2,
since the second phase presumably of K2WO4 was detected for x = 0.3. For all the
substituted samples up to x = 0.4, a large jump in conductivity has been observed
around 500 °C. At higher temperatures, oxide ion conduction is found to be
predominant even for x = 0.4, exceeding the solution limit estimated from the
room-temperature XRD. The conductivity at high temperature is essentially
proportional to the amount of substituted potassium ions up to x = 0.4,
indicating that oxide ion conduction is associated with the formed oxide ion
vacancy. High-temperature X-ray diffraction detected no apparent change in
lattice parameters around 500 °C for x = 0.1, and the remaining second phase
seems to be incorporated into the Scheelite lattice at high temperatures.
PMID- 29954063
TI - Cellular Receptors of Amyloid beta Oligomers (AbetaOs) in Alzheimer's Disease.
AB - It is estimated that Alzheimer’s disease (AD) affects tens of millions of
people, comprising not only suffering patients, but also their relatives and
caregivers. AD is one of age-related neurodegenerative diseases (NDs)
characterized by progressive synaptic damage and neuronal loss, which result in
gradual cognitive impairment leading to dementia. The cause of AD remains still
unresolved, despite being studied for more than a century. The hallmark
pathological features of this disease are senile plaques within patients’
brain composed of amyloid beta (Aβ) and neurofibrillary tangles (NFTs) of
Tau protein. However, the roles of Aβ and Tau in AD pathology are being
questioned and other causes of AD are postulated. One of the most interesting
theories proposed is the causative role of amyloid β oligomers (AβOs)
aggregation in the pathogenesis of AD. Moreover, binding of AβOs to cell
membranes is probably mediated by certain proteins on the neuronal cell surface
acting as AβO receptors. The aim of our paper is to describe alternative
hypotheses of AD etiology, including genetic alterations and the role of
misfolded proteins, especially Aβ oligomers, in Alzheimer’s disease.
Furthermore, in this review we present various putative cellular AβO
receptors related to toxic activity of oligomers.
PMID- 29954068
TI - Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars.
AB - Hepatitis C virus (HCV), the etiological agent of the most common and dangerous
diseases of the liver, is a major health problem worldwide. Despite many
attempts, there is still no vaccine available. Although many drugs have been
approved for use mostly in combination regimen, their high costs make them out of
reach in less developed regions. Previously, we have synthesized a series of
compounds belonging to uridine derivatives of 2-deoxy sugars and have proved that
some of them possess antiviral activity against influenza A virus associated with
N-glycosylation inhibition. Here, we analyze the antiviral properties of these
compounds against HCV. Using cell culture-derived HCV (HCVcc), HCV
pseudoparticles (HCVpp), and replicon cell lines, we have shown high anti-HCV
activity of two compounds. Our results indicated that compounds 2 and 4
significantly reduced HCVcc propagation with IC50 values in low μM range.
Further experiments using the HCVpp system confirmed that both compounds
significantly impaired the infectivity of produced HCVpp due to the inhibition of
the correct maturation of viral glycoproteins. Overall, our results suggest that
inhibiting the glycosylation process might be a good target for new therapeutics
not only against HCV, but other important viral pathogens which contain envelopes
with highly glycosylated proteins.
PMID- 29954069
TI - Generation of Gellan Gum-Based Adipose-Like Microtissues.
AB - Adipose tissue is involved in many physiological processes. Therefore, the need
for adipose tissue-like analogues either for soft tissue reconstruction or as in
vitro testing platforms is undeniable. In this work, we explored the natural
features of gellan gum (GG) to recreate injectable stable adipose-like
microtissues. GG hydrogel particles with different percentages of polymer (0.5%,
0.75%, 1.25%) were developed and the effect of obtained mechanical properties
over the ability of hASCs to differentiate towards the adipogenic lineage was
evaluated based on the expression of the early (PPARγ) and late (FABP4)
adipogenic markers, and on lipids formation and accumulation. Constructs were
cultured in adipogenic induction medium up to 21 days or for six days in
induction plus nine days in maintenance media. Overall, no significant
differences were observed in terms of hASCs adipogenic differentiation within the
range of Young’s moduli between 2.7 and 12.9 kPa. The long-term (up to six
weeks) stability of the developed constructs supported its application in soft
tissue reconstruction. Moreover, their ability to function as adipose-like
microtissue models for drug screening was demonstrated by confirming its
sensitivity to TNFα and ROCK inhibitor, respectively involved in the
repression and induction of the adipogenic differentiation.
PMID- 29954070
TI - Association between Dietary Inflammatory Index, C-Reactive Protein and Metabolic
Syndrome: A Cross-Sectional Study.
AB - Increased prevalence of metabolic syndrome (MetS) has become a global major
public health problem. Chronic low-grade inflammation associated with diet was
found to play an import role in the development of MetS, although further studies
are needed. The main purpose of this study was to explore the association between
the dietary inflammatory index (DII), C-reactive protein (CRP) as a sign of
inflammation status, and MetS. A total of 1712 participants from eight cities in
China were included. Sociodemographic and health-related information was
collected by a self-administrated questionnaire. Anthropometric information and
fasting blood samples were collected for identification of MetS. DII scores were
computed based on one time 24-h dietary recall. No significant association
between MetS and DII was observed except for the blood pressure component of MetS
(OR T3 versus T1 = 1.40; 95% CI: 1.03 to 1.89). A significant increased
prevalence for MetS was observed for higher CRP (OR = 1.66; 95% CI: 1.26 to
2.18), as well as four out of five of MetS components. In stratified analyses by
sex, the associations between DII/CRP and MetS among women, but not men, are
comparable to the whole sample. In addition, Both the 2nd and 3rd tertile of the
DII had a higher CRP level (β-Coefficients T2 versus T1 = 0.086, 95% CI:
0.004 to 0.167; β-Coefficients T3 versus T1 = 0.145, 95% CI: 0.045 to 0.245)
among subjects with MetS. Participants with higher DII scores reported a higher
degree of “Shanghuo” (p = 0.007), which is a traditional concept
characterized by “redness, swelling, fever and pain” in Chinese
Medicine. This study suggested a close association between CRP and MetS, while
the association between the DII and MetS was limited. DII was only specifically
associated with CRP at a higher level among participants with MetS.
PMID- 29954072
TI - "Good Guys Don't Rape": Greek and Non-Greek College Student Perpetrator Rape
Myths.
AB - The current study examined sexual assault perpetrator rape myths among college
students, and in particular Greek students. Fraternity men are overrepresented
among sexual assault perpetrators, while sorority women are at increased risk for
victimization of sexual assault. The current study examined Greek-affiliated and
non-Greek-affiliated perceptions of perpetrator rape myths among 892 college
students; 58% of the sample was Greek-affiliated. Men and Greek-affiliated
students reported higher agreement on stereotypes than women and non-Greek
affiliated students regarding perpetrator rape myths. Specifically, fraternity
men reported higher stereotypical perceptions compared to all women and non
affiliated men, while there was no difference between sorority and non-affiliated
women.
PMID- 29954071
TI - Burkholderia Lethal Factor 1, a Novel Anti-Cancer Toxin, Demonstrates Selective
Cytotoxicity in MYCN-Amplified Neuroblastoma Cells.
AB - Immunotoxins are being investigated as anti-cancer therapies and consist of a
cytotoxic enzyme fused to a cancer targeting antibody. All currently used toxins
function via the inhibition of protein synthesis, making them highly potent in
both healthy and transformed cells. This non-specific cell killing mechanism
causes dose-limiting side effects that can severely limit the potential of
immunotoxin therapy. In this study, the recently characterised bacterial toxin
Burkholderia lethal factor 1 (BLF1) is investigated as a possible alternative
payload for targeted toxin therapy in the treatment of neuroblastoma. BLF1
inhibits translation initiation by inactivation of eukaryotic initiation
translation factor 4A (eIF4A), a putative anti-cancer target that has been shown
to regulate a number of oncogenic proteins at the translational level. We show
that cellular delivery of BLF1 selectively induces apoptosis in neuroblastoma
cells that display MYCN amplification but has little effect on non-transformed
cells. Future immunotoxins based on this enzyme may therefore have higher
specificity towards MYCN-amplified cancer cells than more conventional ribosome
inactivating proteins, leading to an increased therapeutic window and decreased
side effects.
PMID- 29954073
TI - The Microstructure-Mechanical Properties of Hybrid Fibres-Reinforced Self
Compacting Lightweight Concrete with Perlite Aggregate.
AB - The purpose of this paper is to determine the influence of the lightweight porous
perlite aggregate and two widely used types of fibres on the physical and
mechanical properties, frost durability and microstructure of self-compacting
lightweight concrete (SCLC). The experimental investigation consisted of tests
carried out on cubes and prismatic samples made of SCLC and fibres-reinforced
SCLC with variable content ranging from 0.5 to 1% of basalt fibres (BF) and/or
0.5% of steel fibres (SF). In this study, two variable contents of fine perlite
aggregate were used: 5% and 15%. The workability (the slump-flow and t500 values)
in fresh state SCLCs have been done. Extensive data on compressive and flexural
tensile strength in bending behaviour, frost resistance and the microstructure
including interfacial transition zone (ITZ) were recorded and analysed. The
hybrid fibres-reinforced SCLC with perlite aggregate showed a more ductile
behaviour compared to that of SCLC without fibres. Fibres bridge cracks during
flexural tensile strength test. BF successfully protected porous SCLC against
frost attack, whereas SF succumbed to damage.
PMID- 29954074
TI - Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Mass
Spectrometry for Therapeutic Drug Monitoring of Metformin and Rosuvastatin in
Human Plasma.
AB - In this work a hydrophilic interaction liquid chromatography/positive ion
electrospray mass spectrometric assay (HILIC/ESI-MS) has been developed and fully
validated for the quantitation of metformin and rosuvastatin in human plasma.
Sample preparation involved the use of 100 μL of human plasma, following
protein precipitation and filtration. Metformin, rosuvastatin and 4-[2
(propylamino) ethyl] indoline 2 one hydrochloride (internal standard) were
separated by using an X-Bridge-HILIC BEH analytical column (150.0 × 2.1 mm
i.d., particle size 3.5 μm) with isocratic elution. A mobile phase consisting
of 12% (v/v) 15 mM ammonium formate water solution in acetonitrile was used for
the separation and pumped at a flow rate of 0.25 mL min−1. The linear range
of the assay was 100 to 5000 ng mL−1 and 2 to 100 ng mL−1 for
metformin and rosuvastatin, respectively. The current HILIC-ESI/MS method allows
for the accurate and precise quantitation of metformin and rosuvastatin in human
plasma with a simple sample preparation and a short a chromatographic run time
(less than 15 min). Plasma samples from eight patients were further analysed
proving the capability of the proposed method to support a wide range of clinical
studies.
PMID- 29954075
TI - Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin
Promotes Synergistic Anti-Tumoral Activity.
AB - Doxorubicin is a cytotoxic drug used for the treatment of many cancer types.
However, its significant dose-related adverse effects including cardiotoxicity
may hamper its efficiency. Moreover, the multidrug resistance that appears during
treatments limits anti-cancer therapies. Hyperthermia has been introduced as an
adjuvant anti-cancer therapy and presents promising opportunities especially in
combination with chemotherapy. However, hyperthermia methods including standard
magnetic hyperthermia do not discriminate between the target and the surrounding
normal tissues and can lead to side effects. In this context, a Magnetic Intra
Lysosomal Hyperthermia (MILH) approach, which occurs without perceptible
temperature rise, has been developed. We previously showed that minute amounts of
iron oxide magnetic nanoparticles targeting the gastrin receptor (CCK2R) are
internalized by cancer cells through a CCK2R-dependent physiological process,
accumulated into their lysosomes and kill cancer cells upon high frequency
alternating magnetic field (AMF) application through lysosomal cell death. Here,
we show that the combination of MILH with doxorubicin increases the efficiency of
the eradication of endocrine tumor cells with synergism. We also demonstrate that
these two treatments activate two different cell death pathways that are
respectively dependent on Caspase-1 and Caspase-3 activation. These findings will
result in the development of new anti-tumoral, intra-lysosomal
thermo/chemotherapy with better curative effects than chemotherapy alone and that
are devoid of adverse effects linked to standard hyperthermia approaches.
PMID- 29954077
TI - Optimization of the Iron Ore Direct Reduction Process through Multiscale Process
Modeling.
AB - Iron ore direct reduction is an attractive alternative steelmaking process in the
context of greenhouse gas mitigation. To simulate the process and explore
possible optimization, we developed a systemic, multiscale process model. The
reduction of the iron ore pellets is described using a specific grain model,
reflecting the transformations from hematite to iron. The shaft furnace is
modeled as a set of interconnected one-dimensional zones into which the principal
chemical reactions (3-step reduction, methane reforming, Boudouard and water gas
shift) are accounted for with their kinetics. The previous models are finally
integrated in a global, plant-scale, model using the Aspen Plus software. The
reformer, scrubber, and heat exchanger are included. Results at the shaft furnace
scale enlighten the role of the different zones according to the physico-chemical
phenomena occurring. At the plant scale, we demonstrate the capabilities of the
model to investigate new operating conditions leading to lower CO2 emissions.
PMID- 29954076
TI - GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling.
AB - G protein-coupled receptors (GPCRs) are a large diverse family of cell surface
signaling receptors implicated in various types of cancers. Several studies
indicate that GPCRs control many aspects of cancer progression including tumor
growth, invasion, migration, survival and metastasis. While it is known that GPCR
activity can be altered in cancer through aberrant overexpression, gain-of
function activating mutations, and increased production and secretion of
agonists, the precise mechanisms of how GPCRs contribute to cancer progression
remains elusive. Protease-activated receptors (PARs) are a unique class of GPCRs
implicated in cancer. PARs are a subfamily of GPCRs comprised of four members
that are irreversibly activated by proteolytic cleavage induced by various
proteases generated in the tumor microenvironment. Given the unusual proteolytic
irreversible activation of PARs, expression of receptors at the cell surface is a
key feature that influences signaling responses and is exquisitely controlled by
endocytic adaptor proteins. Here, we discuss new survey data from the Cancer
Genome Atlas and the Genotype-Tissue Expression projects analysis of expression
of all PAR family member expression in human tumor samples as well as the role
and function of the endocytic sorting machinery that controls PAR expression and
signaling of PARs in normal cells and in cancer.
PMID- 29954078
TI - Regulation of Root Development and Architecture by Strigolactones under Optimal
and Nutrient Deficiency Conditions.
AB - Strigolactones (SLs) constitute a group of plant hormones which are involved in
multiple aspects of plant growth and development. Beside their role in shoot and
root development and plant architecture in general, SLs are also involved in
plant responses to nutrient deficiency by promoting interactions with symbiotic
organisms and via promotion of root elongation. Recent observations on the cross
talk between SLs and other hormones demonstrate that the inhibition of
adventitious root formation by ethylene is independent of SLs. Additionally, it
was shown that root exposure to SLs leads to the accumulation of secondary
metabolites, such as flavonols or antioxidants. These data suggest pleiotropic
effects of SLs, that influence root development. The discovery that the commonly
used synthetic SL analogue racGR24 might also mimic the function of other plant
growth regulators, such as karrikins, has led us to consider the previously
published publications under the new aspects. This review summarizes present
knowledge about the function of SLs in shaping root systems under optimal and
nutrient deficiency conditions. Results which appear inconsistent with the
various aspects of root development are singled out.
PMID- 29954080
TI - Detection of Cattle Using Drones and Convolutional Neural Networks.
AB - Multirotor drones have been one of the most important technological advances of
the last decade. Their mechanics are simple compared to other types of drones and
their possibilities in flight are greater. For example, they can take-off
vertically. Their capabilities have therefore brought progress to many
professional activities. Moreover, advances in computing and telecommunications
have also broadened the range of activities in which drones may be used.
Currently, artificial intelligence and information analysis are the main areas of
research in the field of computing. The case study presented in this article
employed artificial intelligence techniques in the analysis of information
captured by drones. More specifically, the camera installed in the drone took
images which were later analyzed using Convolutional Neural Networks (CNNs) to
identify the objects captured in the images. In this research, a CNN was trained
to detect cattle, however the same training process could be followed to develop
a CNN for the detection of any other object. This article describes the design of
the platform for real-time analysis of information and its performance in the
detection of cattle.
PMID- 29954079
TI - The Osteoclast in Bone Metastasis: Player and Target.
AB - Bone metastases are frequently the final fate of breast and prostate cancer
patients. According to the definition of metastasis as an incurable disease, to
date there are no effective treatments for tumor-associated bone metastases and
this represents a real challenge for the researchers in the field. The bone is a
heterogeneous environment that represents a fertile soil for tumor cells,
supporting their growth. Among the different cell types present in the bone, in
this review we will focus our attention on the osteoclasts, which are crucial
players in the so called “vicious cycle”, a phenomenon triggered by
tumor cells eventually leading to both tumor proliferation as well as bone
deregulation, thus fueling the development of bone metastasis. The complex
network, linking tumor cells to the bone by activating osteoclasts, represents a
fruitful target for the treatment of bone metastases. In this review we will
describe how tumor cells perturb the bone microenvironment by actively
influencing osteoclast formation and activity. Moreover, we will describe the
current antiresorptive drugs employed in the treatment of bone metastases as well
as new, targeted therapies able to affect both cancer cells and osteoclasts.
PMID- 29954081
TI - Display of Porcine Epidemic Diarrhea Virus Spike Protein on Baculovirus to
Improve Immunogenicity and Protective Efficacy.
AB - A new variant of the porcine epidemic diarrhea virus (PEDV) is an emerging swine
disease, killing considerable numbers of neonatal piglets in North America and
Asia in recent years. To generate immunogens mimicking the complex spike (S)
protein folding with proper posttranslational modification to mount a robust
immune response against the highly virulent PEDV, two baculoviruses displaying
the full-length S protein (S-Bac) and the S1 protein (S1-Bac) of the virulent
Taiwan genotype 2b (G2b) PEDV Pintung 52 (PEDV-PT) strain were constructed.
Intramuscular immunizations of mice and piglets with the S-Bac and S1-Bac
demonstrated significantly higher levels of systemic anti-PEDV S-specific IgG, as
compared with control group. Our results also showed that piglets in the S-Bac
group elicited superior PEDV-specific neutralizing antibodies than those of the
S1-Bac and control groups. The highly virulent PEDV-PT strain challenge
experiment showed that piglets immunized with S-Bac and S1-Bac showed milder
clinical symptoms with significantly less fecal viral shedding as compared with
non-immunized control piglets. More importantly, piglets immunized with the S-Bac
exhibited no to mild clinical signs, with a delayed, minimal viral shedding. Our
results demonstrated that the S-Bac could serve as a safe, easy to manipulate,
and effective vaccine candidate against the PEDV infection.
PMID- 29954082
TI - Sensitive Spectroscopy of Acetone Using a Widely Tunable External-Cavity Quantum
Cascade Laser.
AB - We employed a single-mode, widely tunable (~300 cm−1) external-cavity
quantum cascade laser operating around 8 µm for broadband direct absorption
spectroscopy and wavelength modulation spectroscopy where a modulation frequency
of 50 kHz was employed with high modulation amplitudes of up to 10 GHz. Using a
compact multipass cell, we measured the entire molecular absorption band of
acetone at ~7.4 µm with a spectral resolution of ~1 cm−1. In
addition, to demonstrate the high modulation dynamic range of the laser, we
performed direct absorption (DAS) and second harmonic wavelength modulation
spectroscopy (WMS-2f) of the Q-branch peak of acetone molecular absorption band
(HWHM ~10 GHz) near 1365 cm−1. With WMS-2f, a minimum detection limit of 15
ppbv in less than 10 s is achieved, which yields a noise equivalent absorption
sensitivity of 1.9 × 10−8 cm−1 Hz−1/2.
PMID- 29954083
TI - Pheromone-Trap Monitoring System for Pea Leaf Weevil, Sitona lineatus: Effects of
Trap Type, Lure Type and Trap Placement within Fields.
AB - The pea leaf weevil, Sitona lineatus, is an important pest of field peas and faba
beans worldwide. Present sampling techniques that rely on detection of adult
feeding damage are labor intensive, time consuming and require repeated sampling.
Semiochemical-based pest monitoring systems could improve pea leaf weevil
management. This study, which was conducted in the Golden Triangle region of
Montana, tested several factors that potentially might affect capture rates of
pheromone-baited traps, including trap and lure type and trap placement.
Pheromone-baited pitfall and ramp traps caught significantly more adults than
ground or delta traps, in all study areas. Pitfall traps baited with gray rubber
septa captured significantly more adults than traps baited with membrane
formulations or controls in both pea and lentil fields. In addition, pheromone
baited pitfall traps positioned in the southern part of pea fields captured
relatively higher numbers of adults than those placed in northern parts of
fields, although this difference was not significant. These findings can be used
to improve adult weevil monitoring and should be taken into consideration when
developing an integrated pest management program.
PMID- 29954085
TI - Electrospun Oxygen Scavenging Films of Poly(3-hydroxybutyrate) Containing
Palladium Nanoparticles for Active Packaging Applications.
AB - This paper reports on the development and characterization of oxygen scavenging
films made of poly(3-hydroxybutyrate) (PHB) containing palladium nanoparticles
(PdNPs) prepared by electrospinning followed by annealing treatment at 160
°C. The PdNPs were modified with the intention to optimize their dispersion
and distribution in PHB by means of two different surfactants permitted for food
contact applications, i.e., hexadecyltrimethylammonium bromide (CTAB) and
tetraethyl orthosilicate (TEOS). Analysis of the morphology and characterization
of the chemical, thermal, mechanical, and water and limonene vapor barrier
properties and the oxygen scavenging capacity of the various PHB materials were
carried out. From the results, it was seen that a better dispersion and
distribution was obtained using CTAB as the dispersing aid. As a result, the
PHB/PdNP nanocomposites containing CTAB provided also the best oxygen scavenging
performance. These films offer a significant potential as new active coating or
interlayer systems for application in the design of novel active food packaging
structures.
PMID- 29954087
TI - The Use of Colors as an Alternative to Size in Fusarium graminearum Growth
Studies.
AB - Size-based fungal growth studies have limitations. For example, the growth in
size stops in closed systems once it reaches the borders and poorly describes
metabolic status, especially in the stationary phase. This might lead mycotoxin
studies to unrealistic results. Color change could be a viable alternative, as
pigments result from a mold’s metabolic activity. This study aimed to
verify the possibility of using gray values and the RGB system to analyze the
growth of Fusarium graminearum. It consisted of color and area measurements using
ImageJ software for specimens grown in yeast extract agar (YEA). The results
suggest the utility of color and gray values as reliable tools to analyze the
growth of F. graminearum.
PMID- 29954086
TI - Antifungal and Cytotoxic Activities of Sixty Commercially-Available Essential
Oils.
AB - There is an urgent and unmet need for new antifungal therapies. Global fungal
infection rates continue to rise and fungal infections pose increasing burdens on
global healthcare systems. Exacerbating the situation, the available antifungal
therapeutic arsenal is limited and development of new antifungals has been slow.
Current antifungals are known for unwanted side effects including nephrotoxicity
and hepatotoxicity. Thus, the need for new antifungals and new antifungal targets
is urgent and growing. A collection of 60 commercially-available essential oils
has been screened for antifungal activity against Aspergillus niger, Candida
albicans, and Cryptococcus neoformans, as well as for cytotoxic activity against
MCF-7 and MDA-MB-231 human breast tumor cell lines; the chemical compositions of
the essential oils have been determined by gas chromatography-mass spectrometry
(GC-MS). Ten essential oils showed remarkable antifungal and cytotoxic
activities: Indian, Australian, and Hawaiian sandalwoods; melissa; lemongrass;
cilantro; cassia; cinnamon; patchouli; and vetiver.
PMID- 29954084
TI - Contribution of Epstein-Barr Virus Latent Proteins to the Pathogenesis of
Classical Hodgkin Lymphoma.
AB - Pathogenic viruses have evolved to manipulate the host cell utilising a variety
of strategies including expression of viral proteins to hijack or mimic the
activity of cellular functions. DNA tumour viruses often establish latent
infection in which no new virions are produced, characterized by the expression
of a restricted repertoire of so-called latent viral genes. These latent genes
serve to remodel cellular functions to ensure survival of the virus within host
cells, often for the lifetime of the infected individual. However, under certain
circumstances, virus infection may contribute to transformation of the host cell;
this event is not a usual outcome of infection. Here, we review how the Epstein
Barr virus (EBV), the prototypic oncogenic human virus, modulates host cell
functions, with a focus on the role of the EBV latent genes in classical Hodgkin
lymphoma.
PMID- 29954089
TI - 3D Magnetic Field Reconstruction Methodology Based on a Scanning Magnetoresistive
Probe.
AB - The present work provides a detailed description on quantitative 3D magnetic
field reconstruction using a scanning magnetoresistance microscopy setup
incorporating a 19.5 μm × 2.5 μm magnetoresistive sensor. Therefore,
making use of a rotation stage, 11 nm thick ferromagnetic CoFe elements with 20
μm × 5 μm planar size were measured along different sensor axes and
converted into cartesian coordinate magnetic field components by use of the
analytical coordinate transform equations. The reconstruction steps were followed
and validated by numerical simulations based on a field averaging model caused by
a non-negligible sensor volume. Detailed in-plane magnetic component
reconstruction with ability to reconstruct sub-micrometer features is achieved. A
discussion on the limiting factors for optimal resolution is presented.
PMID- 29954088
TI - In Silico Screening of Isocitrate Lyase for Novel Anti-Buruli Ulcer Natural
Products Originating from Africa.
AB - Buruli ulcer (BU) is caused by Mycobacterium ulcerans and is predominant in both
tropical and subtropical regions. The neglected debilitating disease is
characterized by chronic necrotizing skin lesions attributed to a mycolactone,
which is a macrolide toxin secreted by M. ulcerans. The preferred treatment is
surgical excision of the lesions followed by a prolonged combination antibiotic
therapy using existing drugs such as rifampicin and streptomycin or
clarithromycin. These antibiotics appear not to be adequately potent and
efficacious against persistent and late stage ulcers. In addition, emerging drug
resistance to treatment poses great challenges. There is a need to identify novel
natural product-derived lead compounds, which are potent and efficacious for the
treatment of Buruli ulcer. Natural products present a rich diversity of chemical
compounds with proven activity against various infectious diseases, and
therefore, are considered in this study. This study sought to computationally
predict natural product-derived lead compounds with the potential to be developed
further into potent drugs with better therapeutic efficacy than the existing anti
buruli ulcer compounds. The three-dimensional (3D) structure of Isocitrate lyase
(ICL) of Mycobacterium ulcerans was generated using homology modeling and was
further scrutinized with molecular dynamics simulations. A library consisting of
885 compounds retrieved from the AfroDb database was virtually screened against
the validated ICL model using AutoDock Vina. AfroDb is a compendium of
“drug-like” and structurally diverse 3D structures of natural
products originating from different geographical regions in Africa. The molecular
docking with the ICL model was validated by computing a Receiver Operating
Characteristic (ROC) curve with a reasonably good Area Under the Curve (AUC)
value of 0.89375. Twenty hit compounds, which docked firmly within the active
site pocket of the ICL receptor, were assessed via in silico bioactivity and
pharmacological profiling. The three compounds, which emerged as potential novel
leads, comprise ZINC38143792 (Euscaphic acid), ZINC95485880, and ZINC95486305
with reasonable binding energies (high affinity) of −8.6, −8.6, and
−8.8 kcal/mol, respectively. Euscaphic acid has been reported to show
minimal inhibition against a drug-sensitive strain of M. tuberculosis. The other
two leads were both predicted to possess dermatological activity while one was
antibacterial. The leads have shown promising results pertaining to efficacy,
toxicity, pharmacokinetic, and safety. These leads can be experimentally
characterized to assess their anti-mycobacterial activity and their scaffolds may
serve as rich skeletons for developing anti-buruli ulcer drugs.
PMID- 29954091
TI - Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity.
AB - Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp. that causes
Fusarium head blight (FHB) disease in cereal crops. Ingestion of food
contaminated with DON poses serious human health complications. However, the DON
cytotoxicity has been mostly deduced from animal studies. In this study, we used
the nematode Caenorhabditis elegans (C. elegans) as a tractable animal model to
dissect the toxic effect of DON. Our results indicate that DON reduces the
fecundity and lifespan of C. elegans. Real-time quantitative polymerase chain
reaction (RT-qPCR) analysis showed that DON upregulates innate immunity-related
genes including C17H12.8 and K08D8.5 encoding PMK-1 (mitogen activated protein
kinase-1)-regulated immune effectors, and F35E12.5 encoding a CUB-like domain
containing protein. Furthermore, our RNAseq data demonstrate that out of ~17,000
C. elegans genes, 313 are upregulated and 166 were downregulated by DON
treatment. Among the DON-upregulated genes, several are ugt genes encoding UDP
glucuronosyl transferase (UGTs) which are known to be involved in chemical
detoxification. The three upregulated genes, F52F10.4 (oac-32), C10H11.6 (ugt-26)
and C10H11.4 (ugt-28) encoding the O-acyltransferase homolog, UGT26 and UGT 28,
respectively, are shown to contribute to DON tolerance by a RNAi bacterial
feeding experiment. The results of this study provide insights to the targets of
DON cytotoxicity and potential mitigation measures.
PMID- 29954090
TI - Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved
from 2013 to 2017 in Controlling HbA1c in Diabetes Patients.
AB - Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes mellitus and
accounts for about 95% of all diabetes cases. Many newer oral as well as
parenteral antidiabetic drugs have been introduced in to the market in recent
years to control hyperglycemic conditions in diabetes patients and many of these
drugs produce potential side effects in diabetes patients. Hence, this systematic
review was aimed to analyze and compare the efficacy and safety of oral
antidiabetic agents in controlling HbA1c in T2DM patients, that were approved by
the United States-Food and Drug Administration (US-FDA) from 2013 to 2017. All
randomized controlled, double-blind trials published in English during the search
period involving the newer antidiabetic agents were selected. In the outcome
assessment comparison, semaglutide demonstrated the highest efficacy in lowering
HbA1c, with a 1.6% reduction (p < 0.0001) when given at a dose of 1.0 mg. The
safety profile of all the agents as compared to placebo or control were similar,
with no or slight increase in the occurrence of adverse events (AEs) but no fatal
reaction was reported. The most common AEs of all the antidiabetic agents were
gastrointestinal in nature, with several cases of hypoglycemic events. However,
among all these agents, semaglutide seems to be the most efficacious drug to
improve glycemic control in terms of HbA1c. Alogliptin has the least overall
frequency of AEs compared to other treatment groups.
PMID- 29954092
TI - Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a
Recombinant Baculovirus Co-Expressing S1 and N Proteins.
AB - Avian infectious bronchitis virus (IBV) is the causative agent of infectious
bronchitis, which results in considerable economic losses. It is imperative to
develop safe and efficient candidate vaccines to control IBV infection. In the
current study, recombinant baculoviruses co-expressing the S1 and N proteins and
mono-expressing S1 or N proteins of the GX-YL5 strain of IBV were constructed and
prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of
immune protection of these subunit vaccines were evaluated by inoculating
specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster
with the same dose 14 days later and challenging them with a virulent GX-YL5
strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was
used as a control. The IBV-specific antibody levels, as well as the percentages
of CD4+ and CD8+ T lymphocytes, were detected within 28 days post-vaccination
(dpv). The morbidity, mortality and re-isolation of the virus from the tracheas
and kidneys of challenged birds were evaluated at five days post-challenge (dpc).
The results showed that the IBV-specific antibody levels and the percentages of
CD4+ and CD8+ T lymphocytes were higher in the rHBM-S1-N vaccinated birds
compared to birds vaccinated with the rHBM-S1 and rHBM-N vaccines. At 5 dpc, the
mortality, morbidity and virus re-isolation rate of the birds vaccinated with the
rHBM-S1-N vaccine were slightly higher than those vaccinated with the H120
control vaccine but were lower than those vaccinated with the rHBM-S1 and rHBM-N
vaccines. The present study demonstrated that the protection of the recombinant
baculovirus co-expressing S1 and N proteins was better than that of recombinant
baculoviruses mono-expressing the S1 or N protein. Thus, the recombinant
baculovirus co-expressing S1 and N proteins could serve as a potential IBV
vaccine and this demonstrates that the bivalent subunit vaccine including the S1
and N proteins might be a strategy for the development of an IBV subunit vaccine.
PMID- 29954093
TI - Ferrocenes as Building Blocks in Molecular Rectifiers and Diodes.
AB - Ferrocenes have recently been reported as components of a number of molecular
circuits. This short review covers reports of ferrocenes in molecular rectifiers
and diodes which have appeared in the last 10 years.
PMID- 29954094
TI - Analysis and Improvement of a Dual-Core Photonic Crystal Fiber Sensor.
AB - The characteristics of the dual-core photonic crystal fiber (PCF) sensor are
studied using the finite element method (FEM), and the structure is improved
according to the numerical simulation results. The results show that whether or
not the four large air holes far away from the geometry center of the PCF are
filled with analyte has no influence on the wavelength sensitivity of the sensor
which means those holes can be replaced by small air holes. The wavelength
sensitivity can be tuned by adjusting the sizes of the other large air holes
which are as for liquid holes. The dynamic detection range of the refractive
index (RI) is from 1.33 to 1.51. In particular, high linearity is obtained in the
range of 1.44 to 1.51. The sensitivity is as high as 6021 nm/RIU when the liquid
holes are the smallest. When liquid holes are tangential with the envelope of
first layer air holes, the wavelength sensitivity is 4028 nm/RIU, and the
coefficient of determination (R2) is 0.99822 when the RI of the analyte varies
from 1.44 to 1.51 which shows that high sensitivity and good linearity are both
obtained.
PMID- 29954096
TI - Horizontal Transfer of Symbiosis Genes within and Between Rhizobial Genera:
Occurrence and Importance.
AB - Rhizobial symbiosis genes are often carried on symbiotic islands or plasmids that
can be transferred (horizontal transfer) between different bacterial species.
Symbiosis genes involved in horizontal transfer have different phylogenies with
respect to the core genome of their ‘host’. Here, the literature on
legume-rhizobium symbioses in field soils was reviewed, and cases of phylogenetic
incongruence between rhizobium core and symbiosis genes were collated. The
occurrence and importance of horizontal transfer of rhizobial symbiosis genes
within and between bacterial genera were assessed. Horizontal transfer of
symbiosis genes between rhizobial strains is of common occurrence, is widespread
geographically, is not restricted to specific rhizobial genera, and occurs within
and between rhizobial genera. The transfer of symbiosis genes to bacteria adapted
to local soil conditions can allow these bacteria to become rhizobial symbionts
of previously incompatible legumes growing in these soils. This, in turn, will
have consequences for the growth, life history, and biogeography of the legume
species involved, which provides a critical ecological link connecting the
horizontal transfer of symbiosis genes between rhizobial bacteria in the soil to
the above-ground floral biodiversity and vegetation community structure.
PMID- 29954097
TI - Diet-Quality and Socio-Demographic Factors Associated with Non-Nutritive
Sweetener Use in the Australian Population.
AB - Non-nutritive sweeteners (NNS) are used in the food supply to replace sugar
and/or to reduce dietary energy intake. The aim of this research was to assess
the consumption prevalence and food sources of NNS in the Australian population.
Food group and nutrient intakes were assessed to compare diet quality of NNS
consumers and non-consumers. Secondary analysis of the Australian National
Nutrition and Physical Activity Survey, 2011/12 was conducted (n = 12,435) after
identifying all NNS products consumed in the population. The proportion of
participants that reported intake of NNS per day was 18.2% for adults (19+
years), and 8.5% for children (2-18 years), with the most common food sources
being carbonated soft drinks, tabletop sweeteners, and yoghurt. Characteristics
associated with NNS consumption in adults included being female, higher body mass
index (BMI), self-reported diabetes status, and being on a weight-loss diet. For
adults, NNS consumers had lower free sugar intake but energy intake did not
differ from non-consumers. However, for children, no differences in free sugar or
energy intake were observed between consumers and non-consumers. While these
results support the use of NNS in reducing sugar intake, these data suggest
compensatory increases in energy intake may occur.
PMID- 29954098
TI - Human Exposure to Ferret Badger Rabies in Taiwan.
AB - On 17 July 2013, Taiwan confirmed multiple cases of the rabies virus (RABV) in
the wild Taiwan Ferret badger (TFB) (Melogale moschata) member of the family
Mustelidae. This study aims at investigating the risk factors for human exposure
to rabid TFBs. Statistical inference based on Pearson correlation showed that
there was a strong positive correlation between the total number of positive TFB
rabies cases and the number of rabid TFBs involved with human activities in 81
enzootic townships (r = 0.91; p < 0.001). A logistic regression analysis
indicated that the risk probability of a human being bitten by rabid TFBs was
significantly higher when there were no dogs around (35.55% versus 6.17%
(indoors, n = 171, p = 0.0001), and 52.00% versus 5.26% (outdoors, n = 44, p =
0.021)), and whether or not there was a dog around was the only crucial covariate
that was statistically significantly related to the risk of a human being bitten.
In conclusion, this study showed the value of having vaccinated pets as a
deterrent to TFB encounters and as a buffer to prevent human exposure to rabid
TFBs. The presence of unvaccinated pets could become a significant risk factor in
the longer term if rabies isn’t controlled in TFBs because of the spillover
between the sylvatic and urban cycles of rabies. Consequently, raising dogs, as
well as keeping rabies vaccinations up-to-date for them, can be considered an
effective preventive strategy to reduce the risk for human exposure to rabid
TFBs.
PMID- 29954095
TI - Activating the Anaphase Promoting Complex to Enhance Genomic Stability and
Prolong Lifespan.
AB - In aging cells, genomic instability is now recognized as a hallmark event.
Throughout life, cells encounter multiple endogenous and exogenous DNA damaging
events that are mostly repaired, but inevitably DNA mutations, chromosome
rearrangements, and epigenetic deregulation begins to mount. Now that people are
living longer, more and more late life time is spent suffering from age-related
disease, in which genomic instability plays a critical role. However, several
major questions remain heavily debated, such as the following: When does aging
start? How long can we live? In order to minimize the impact of genomic
instability on longevity, it is important to understand when aging starts, and to
ensure repair mechanisms remain optimal from the very start to the very end. In
this review, the interplay between the stress and nutrient response networks, and
the regulation of homeostasis and genomic stability, is discussed. Mechanisms
that link these two networks are predicted to be key lifespan determinants. The
Anaphase Promoting Complex (APC), a large evolutionarily conserved ubiquitin
ligase, can potentially serve this need. Recent work demonstrates that the APC
maintains genomic stability, mounts a stress response, and increases longevity in
yeast. Furthermore, inhibition of APC activity by glucose and nutrient response
factors indicates a tight link between the APC and the stress/nutrient response
networks.
PMID- 29954099
TI - Identification of Novel HIV-1 Latency-Reversing Agents from a Library of Marine
Natural Products.
AB - Natural products originating from marine and plant materials are a rich source of
chemical diversity and unique antimicrobials. Using an established in vitro model
of HIV-1 latency, we screened 257 pure compounds from a marine natural product
library and identified 4 (psammaplin A, aplysiatoxin, debromoaplysiatoxin, and
previously-described alotaketal C) that induced expression of latent HIV-1
provirus in both cell line and primary cell models. Notably, aplysiatoxin induced
similar levels of HIV-1 expression as prostratin but at up to 900-fold lower
concentrations and without substantial effects on cell viability. Psammaplin A
enhanced HIV-1 expression synergistically when treated in combination with the
protein kinase C (PKC) activator prostratin, but not the histone deacetylase
inhibitor (HDACi) panobinostat, suggesting that psammaplin A functions as a
latency-reversing agent (LRA) of the HDACi class. Conversely, aplysiatoxin and
debromoaplysiatoxin synergized with panobinostat but not prostratin, suggesting
that they function as PKC activators. Our study identifies new compounds from
previously untested marine natural products and adds to the repertoire of LRAs
that can inform therapeutic “shock-and-kill”-based strategies to
eliminate latent HIV-infected reservoirs.
PMID- 29954100
TI - Effect of the Sodium Polyacrylate on the Magnetite Nanoparticles Produced by
Green Chemistry Routes: Applicability in Forward Osmosis.
AB - Aqueous dispersions of magnetic nanocomposites have been proposed as draw
electrolytes in forward osmosis. One possible approach for the production of
nanocomposites based on magnetite nanoparticles and sodium polyacrylate is the
synthesis of the magnetic iron oxide by coprecipitation or oxidative
precipitation in the presence of an excess of the polymer. In this work, we
explored the effect of the polymer proportion on the nanomaterials produced by
these procedures. The materials obtained were compared with those obtained by the
coating of magnetite nanocrystals produced beforehand with the same polymer. The
samples were characterized by chemical analysis, photon correlation spectroscopy,
thermogravimetry, X-ray diffraction, infrared spectroscopy, transmission electron
microscopy, and magnetometry. The general trend observed is that the polymers
heavily modify the texture of the magnetic material during the synthesis, with a
drastic reduction of the particle size and magnetic response. The polycrystalline
texture that is generated permits the incorporation of the polymer both on the
external surface and in the intergranular space. The aqueous dispersions of the
nanocomposites were highly stable, with a hydrodynamic size that was roughly
independent of the polymer/magnetite ratio. Such dispersions show an osmotic
pressure that is proportional to the concentration of the polymer. Interestingly,
the proportionality constant was similar to that of the free polymer only in the
case of the samples prepared by oxidative precipitation, being lower in the case
of the samples prepared by coprecipitation. Finally, the possibilities of using
these materials as draw electrolytes in forward osmosis will be briefly
discussed.
PMID- 29954101
TI - Antidepressant-Like Effect of Lippia sidoides CHAM (Verbenaceae) Essential Oil
and Its Major Compound Thymol in Mice.
AB - Depression is a common disease affecting more than 300 million people worldwide.
Since Lippia sidoides has shown central nervous system effects in previous works,
we aimed to investigate the effect of L. sidoides essential oil and its major
compound, thymol on a corticosterone-induced depression model in mice. Male mice
(20-25 g) received corticosterone (20 mg/kg, subcutaneously), once a day for 22
days. From the 16th day on, mice were grouped to receive either corticosterone or
L. sidoides essential oil (100 and 200 mg/kg), or thymol (25 and 50 mg/kg) or
fluoxetine (35 mg/kg) by gavage. The forced swimming test, tail suspension, open
field, elevated plus maze and sucrose preference tests were performed from the
19th to 22nd day. Data were analyzed by ANOVA followed by the Student-Newman
Keuls as a post hoc test and the results were considered significant when p <
0.05. It was shown that L. sidoides essential oil, thymol and fluoxetine
decreased the immobility time in the tail suspension and forced swimming tests
and none of these altered locomotor activity in the open field test. However, the
drugs increased the amount of grooming. In the elevated plus maze, all drugs
increased the number of entries and the time of permanence in the open arms. In
the sucrose preference test, the L. sidoides essential oil, thymol and fluoxetine
reversed anhedonia. These results suggest that the thymol and L. sidoides
essential oil have an antidepressant-like effect, similar to fluoxetine. However,
future studies should be encouraged to enhance understanding of the effects of
essential oil and thymol for the treatment of depression.
PMID- 29954102
TI - Examining the Nutritional Quality of Canadian Packaged Foods and Beverages with
and without Nutrition Claims.
AB - Nutrient content claims, health claims, and front-of-pack symbols (henceforth
referred to as “nutrition claims” in the present study) are often
found on food labels in Canada. However, it is currently unknown whether foods
and beverages (F&Bs) carrying nutrition claims have a more favourable nutritional
profile than those without such claims. This study examined differences in the
global nutritional quality, as determined by the Food Standards Australia New
Zealand Nutrient Profiling Scoring Criterion (FSANZ-NPSC), of Canadian F&B
bearing nutrition claims as compared to those without, as well as in their
nutritional composition. Data (n = 15,184) was obtained from the University of
Toronto 2013 Food Label Information Program. Forty-two percent of F&Bs carrying
nutrition claims (n = 2930/6990) were found to be ineligible to carry claims
based on the FSANZ-NPSC, in comparison to 66% of F&Bs without (n = 5401/8194, p <
0.001). Sugars and sweets, and miscellaneous products were the food categories
with larger proportions of foods carrying nutrition claims not meeting the FSANZ
NPSC eligibility criteria. F&Bs with nutrition claims had fewer calories, less
saturated fat, sodium, and sugar, and higher content of protein and fibre than
comparable products without nutrition claims (p < 0.05 in all cases). In
conclusion, nearly half of F&Bs carrying nutrition claims in Canada did not meet
the FSANZ-NPSC threshold, although Canadian products carrying nutrition claims
have an overall “healthier” profile than their counterparts without
such claims.
PMID- 29954103
TI - Novel Negative Poisson's Ratio Lattice Structures with Enhanced Stiffness and
Energy Absorption Capacity.
AB - The weak stiffness and strength of materials with negative Poisson's ratio limits
their application. In this paper, three types of novel lattices with negative
Poisson's ratio are proposed to improve not only stiffness and strength but also
energy absorption capacity by embedding different ribs into a classic re-entrant
structure. Unit cell analyses show these novel lattices have significantly
increased Young's modulus along the loading direction, and Type C can maintain
sufficient negative Poisson's ratio performance compared with the base lattice.
In addition, the novel lattices exhibit higher yield stress, plateau stress and
densification strain extracted from quasi-static compressive simulation. The
lattices are prototyped by laser-based additive manufacturing and tested in quasi
static experiments, which show the experimental data match the numerical results
within an error of margin. The work signifies the prospect of lattices with
negative Poisson's ratio in enhancing engineering-applicable structures, and
indicates the potential of structural topology optimization in more sophisticated
designs.
PMID- 29954104
TI - The Role of miR-29a in the Regulation, Function, and Signaling of Liver Fibrosis.
AB - Both fibrosis and cirrhosis of the liver are the end results of most kinds of
chronic liver damage and represent a common but difficult clinical challenge
throughout the world. The inhibition of the fibrogenic, proliferative, and
migratory effects of hepatic stellate cells (HSCs) has become an experimental
therapy for preventing and even reversing hepatic fibrosis. Furthermore, a
complete understanding of the function of non-coding RNA-mediated epigenetic
mechanisms in HSC activation may improve our perception of liver fibrosis
pathogenesis. This review focuses on the evolving view of the molecular
mechanisms by which HSC activation by miR-29a signaling may moderate the
profibrogenic phenotype of these cells, thus supporting the use of miR-29a
agonists as a potential therapy for treating liver fibrosis in the future.
PMID- 29954106
TI - High-Throughput Preparation of Silk Fibroin Nanofibers by Modified Bubble
Electrospinning.
AB - As a kind of natural macromolecular protein molecule extracted from silk, silk
fibroin (SF) has been widely used as biological materials in recent years due to
its good physical and chemical properties. In this paper, a modified bubble
electrospinning (MBE) using a cone-shaped gas nozzle combined with a copper
solution reservoir was applied to obtain high-throughput fabrication of SF
nanofibers. In the MBE process, sodium dodecyl benzene sulfonates (SDBS) were
used as the surfactant to improve the spinnability of SF solution. The
rheological properties and conductivity of the electrospun SF solutions were
investigated. And the effects of gas flow volume, SF solution concentration and
additive amounts of SDBS on the morphology, property and production of SF
nanofibers were studied. The results showed the decrease of gas flow volume could
decrease the nanofiber diameter, enhance the diameter distribution, and increase
the production of nanofibers. And the maximum yield could reach 3.10 g/h at the
SF concentration of 10 wt % and the SDBS concentration of 0.1 wt %.
PMID- 29954105
TI - Meta-Analysis and Systematic Review in Environmental Tobacco Smoke Risk of Female
Lung Cancer by Research Type.
AB - More than 50% of women worldwide are exposed to Environmental Tobacco Smoke
(ETS). The impact of ETS on lung cancer remains unclear. Cohort studies since the
late 1990s have provided new evidence of female lung cancer risk due to ETS. The
objective of this meta-analysis and systematic review was to analyze the
association of ETS with female lung cancer risk from 1997 to 2017, organised
based on research design. According to our applied inclusion and exclusion
criteria, 41 published studies were included. The relative risk (RR) from the
cohort studies or odds ratio (OR) from case-control studies were extracted to
calculate the pooled risks based on the type of study. The summary risks of ETS
were further explored with the modulators of ETS exposure sources and doses. The
pooled risks of lung cancer in non-smoking women exposed to ETS were 1.35 (95%
CI: 1.17-1.56), 1.17 (95% CI: 0.94-1.44), and 1.33 (95% CI: 1.17-1.51) for case
control studies, cohort studies, and both types of studies, respectively. The
summary RR estimate of the cohort studies was not statistically significant, but
the RR increased with increasing doses of ETS exposure (p trend < 0.05). Based on
the results of this study, ETS might be an important risk factor of female lung
cancer in non-smokers.
PMID- 29954108
TI - A Plug-and-Play Human-Centered Virtual TEDS Architecture for the Web of Things.
AB - This article presents a Virtual Transducer Electronic Data Sheet (VTEDS)-based
framework for the development of intelligent sensor nodes with plug-and-play
capabilities in order to contribute to the evolution of the Internet of Things
(IoT) toward the Web of Things (WoT). It makes use of new lightweight protocols
that allow sensors to self-describe, auto-calibrate, and auto-register. Such
protocols enable the development of novel IoT solutions while guaranteeing low
latency, low power consumption, and the required Quality of Service (QoS). Thanks
to the developed human-centered tools, it is possible to configure and modify
dynamically IoT device firmware, managing the active transducers and their
communication protocols in an easy and intuitive way, without requiring any prior
programming knowledge. In order to evaluate the performance of the system, it was
tested when using Bluetooth Low Energy (BLE) and Ethernet-based smart sensors in
different scenarios. Specifically, user experience was quantified empirically
(i.e., how fast the system shows collected data to a user was measured). The
obtained results show that the proposed VTED architecture is very fast, with some
smart sensors (located in Europe) able to self-register and self-configure in a
remote cloud (in South America) in less than 3 s and to display data to remote
users in less than 2 s.
PMID- 29954109
TI - Design, Synthesis and Biological Evaluation of Novel Phenylsulfonylurea
Derivatives as PI3K/mTOR Dual Inhibitors.
AB - Five series of novel phenylsulfonylurea derivatives, 19a-d, 20a-d, 21a-d, 22a-d
and 23a-d, bearing 4-phenylaminoquinoline scaffold were designed, synthesized and
their IC50 values against four cancer cell lines (HepG-2, A549, PC-3 and MCF-7)
were evaluated. Most compounds showed moderate cytotoxicity activity against the
cancer cell lines. Structure-activity relationships (SARs) and pharmacological
results indicated that introduction of 4-aminoquinoline scaffold and
phenylsulfonylurea scaffold were beneficial for anti-tumor activity. Moreover,
para-methoxyl substitution of 4-anilino moiety and para-halogen substitution of
phenylsulfonylurea have different impacts on different series of compounds.
Furthermore, the micromolecule group substitution in the 6-position of the
quinoline ring have a slight impact on the cellular activity of the target
compounds.
PMID- 29954110
TI - Sensitivity Analysis of Geometrical Parameters on the Aerodynamic Performance of
Closed-Box Girder Bridges.
AB - In this study, the influence of two critical geometrical parameters (i.e., angles
of wind fairing, α; and lower inclined web, β) in the aerodynamic
performance of closed-box girder bridges was systematically investigated through
conducting a theoretical analysis and wind tunnel testing using laser
displacement sensors. The results show that, for a particular inclined web angle
β, a closed-box girder with a sharper wind fairing angle of α =
50° has better flutter and vortex-induced vibration (VIV) performance than
that with α = 60°, while an inclined web angle of β = 14°
produces the best VIV performance. In addition, the results from particle image
velocimetry (PIV) tests indicate that a wind fairing angle of α = 50°
produces a better flutter performance by inducing a single vortex structure and a
balanced distribution of the strength of vorticity in both upper and lower parts
of the wake region. Furthermore, two-dimensional three-degrees-of-freedom (2D
3DOF) analysis results demonstrate that the absolute values of Part A (with a
reference of flutter derivative A2*) and Part D (with a reference of A1*H3*)
generally decrease with the increase of β, while the change of the
participation level of heaving degrees of freedom (DOF) in torsion-dominated
coupled flutter initially increases, reaches its peak, and then decreases with
the increase of β.
PMID- 29954111
TI - An Improved Scalable Synthesis of alpha- and beta-Amyrin.
AB - The synthesis of α- and β-amyrin was accomplished starting from easily
accessible starting materials, oleanolic, and ursolic acid. The procedures allow
the preparation of β-amyrin in an exceptionally short scalable manner via
selective iodation and reduction. For α-amyrin, a different synthetic
approach had to be chosen providing access to α-amyrin in medium-to-large
scale.
PMID- 29954107
TI - Systemic Inflammatory Response and Atherosclerosis: The Paradigm of Chronic
Inflammatory Rheumatic Diseases.
AB - Patients with Chronic Inflammatory Rheumatic diseases (CIRD) are at increased
risk of cardiovascular disease (CVD), ascribed not only to classical risk
factors, but also to the presence of chronic systemic inflammatory response.
Αtherosclerosis, the cornerstone of CVD, is known to be accelerated in
CIRD; rheumatoid arthritis promotes atheromatosis and associates with preclinical
atherosclerosis equivalent to Diabetes Mellitus, which also seems to apply for
systemic lupus erythematosus. Data on ankylosing spondylitis and psoriatic
arthritis, albeit more limited, also support an increased CV risk in these
patients. The association between inflammation and atherosclerosis, has been
thoroughly investigated in the last three decades and the role of inflammation in
the pathogenesis and progression of atherogenesis has been well established.
Endothelial dysfunction, oxidative stress in vascular endothelial cells and
macrophage accumulation, toll-like receptor signaling, NLPR-3 formation and
subsequent pro-inflammatory cytokine production, such as TNFa, IL-1β, IL-6,
and TNF-like cytokine 1A, are few of the mechanisms implicated in the atherogenic
process. Moreover, there is evidence that anti-inflammatory biologic drugs, such
as anti-TNF and anti-IL1β agents, can decelerate the atherogenic process,
thus setting new therapeutic targets for early and effective disease control and
suppression of inflammation, in addition to aggressive management of classical CV
risk factors.
PMID- 29954112
TI - Magnetic Porous Molecularly Imprinted Polymers Based on Surface Precipitation
Polymerization and Mesoporous SiO2 Layer as Sacrificial Support for Efficient and
Selective Extraction and Determination of Chlorogenic Acid in Duzhong Brick Tea.
AB - Magnetic porous molecularly imprinted polymers (MPMIPs) for rapid and efficient
selective recognition of chlorogenic acid (CGA) were effectively prepared based
on surface precipitation polymerization using CGA as template, 4-vinylpyridine (4
VP) as functional monomer, and mesoporous SiO2 (mSiO2) layer as sacrificial
support. A computational simulation by evaluation of electronic binding energy is
used to optimize the stoichiometric ratio between CGA and 4-VP (1:5), which
reduced the duration of laboratory trials. The porous MIP shell and the rid of
solid MIPs by magnet gave MPMIPs high binding capacity (42.22 mg/g) and fast
kinetic binding (35 min). Adsorption behavior between CGA and MPMIPs followed
Langmuir equation and pseudo-first-order reaction kinetics. Furthermore, the
obtained MPMIPs as solid phase adsorbents coupled with high performance liquid
chromatography (HPLC) were employed for selective extraction and determination of
CGA (2.93 +/- 0.11 mg/g) in Duzhong brick tea. The recoveries from 91.8% to
104.2%, and the limit of detection (LOD) at 0.8 μg/mL were obtained. The
linear range (2.0-150.0 μg/mL) was wide with R2 > 0.999. Overall, this study
provided an efficient approach for fabrication of well-constructed MPMIPs for
fast and selective recognition and determination of CGA from complex samples.
PMID- 29954113
TI - Isolation of beta-1,3-Glucanase-Producing Microorganisms from Poria cocos
Cultivation Soil via Molecular Biology.
AB - β-1,3-Glucanase is considered as a useful enzymatic tool for β-1,3
glucan degradation to produce (1→3)-linked β-glucan oligosaccharides
with pharmacological activity properties. To validly isolate β-1,3-glucanase
producing microorganisms, the soil of Wolfiporia extensa, considered an
environment rich in β-1,3-glucan-degrading microorganisms, was subjected to
high throughput sequencing. The results demonstrated that the genera Streptomyces
(1.90%) and Arthrobacter (0.78%) belonging to the order Actinomycetales (8.64%)
in the phylum Actinobacteria (18.64%) were observed in soil for P. cocos
cultivation (FTL1). Actinomycetes were considered as the candidates for isolation
of glucan-degrading microorganisms. Out of 58 isolates, only 11 exhibited β
1,3-glucan-degrading activity. The isolate SYBCQL belonging to the genus
Kitasatospora with β-1,3-glucan-degrading activity was found and reported
for the first time and the isolate SYBC17 displayed the highest yield (1.02 U/mg)
among the isolates. To check the β-1,3-glucanase contribution to β-1,3
glucan-degrading activity, two genes, 17-W and 17-Q, encoding β-1,3
glucanase in SYBC17 and one gene QLK1 in SYBCQL were cloned and expressed for
verification at the molecular level. Our findings collectively showed that the
isolates able to secrete β-1,3-glucanase could be obtained with the
assistance of high-throughput sequencing and genes expression analysis. These
methods provided technical support for isolating β-1,3-glucanase-producing
microorganisms.
PMID- 29954115
TI - Shear Elasticity of Magnetic Gels with Internal Structures.
AB - We present the results of the theoretical modeling of the elastic shear
properties of a magnetic gel, consisting of soft matrix and embedded, fine
magnetizable particles, which are united in linear chain-like structures. We
suppose that the composite is placed in a magnetic field, perpendicular to the
direction of the sample shear. Our results show that the field can significantly
enhance the mechanical rigidity of the soft composite. Theoretical results are in
quantitative agreement with the experiments.
PMID- 29954114
TI - Connexin 43 Plays a Role in Pulmonary Vascular Reactivity in Mice.
AB - Pulmonary arterial hypertension (PAH) is a chronic condition characterized by
vascular remodeling and increased vaso-reactivity. PAH is more common in females
than in males (~3:1). Connexin (Cx)43 has been shown to be involved in cellular
communication within the pulmonary vasculature. Therefore, we investigated the
role of Cx43 in pulmonary vascular reactivity using Cx43 heterozygous
(Cx43+/−) mice and 37,43Gap27, which is a pharmacological inhibitor of Cx37
and Cx43. Contraction and relaxation responses were studied in intra-lobar
pulmonary arteries (IPAs) derived from normoxic mice and hypoxic mice using wire
myography. IPAs from male Cx43+/− mice displayed a small but significant
increase in the contractile response to endothelin-1 (but not 5
hydroxytryptamine) under both normoxic and hypoxic conditions. There was no
difference in the contractile response to endothelin-1 (ET-1) or 5
hydroxytryptamine (5-HT) in IPAs derived from female Cx43+/−mice compared
to wildtype mice. Relaxation responses to methacholine (MCh) were attenuated in
IPAs from male and female Cx43+/− mice or by pre-incubation of IPAs with
37,43Gap27. Nω-Nitro-L-arginine methyl ester (l-NAME) fully inhibited MCh
induced relaxation. In conclusion, Cx43 is involved in nitric oxide (NO)-induced
pulmonary vascular relaxation and plays a gender-specific and agonist-specific
role in pulmonary vascular contractility. Therefore, reduced Cx43 signaling may
contribute to pulmonary vascular dysfunction.
PMID- 29954116
TI - Titanium Oxide (TiO2)/Polymethylmethacrylate (PMMA) Denture Base Nanocomposites:
Mechanical, Viscoelastic and Antibacterial Behavior.
AB - Currently, polymethylmethacrylate (PMMA) is the most popular denture base
material. Most fractures of dentures that occur during function are due to its
insufficient mechanical strength. The major drawbacks of PMMA are insufficient
ductility, strength, and viscoelastic behavior. The purpose of this study was to
evaluate a polymethylmethacrylate denture base material modified with TiO2
nanoparticles in terms of nanomechanical, creep-recovery, and relaxation.
Additionally, the effects of addition TiO2 nanoparticles on the thermal and
antimicrobial adhesion behaviors were investigated. Differential scanning
calorimetry and thermogravimetric analysis indicated that the effect of small
amounts of TiO2 nanoparticles (1 wt. %, 2 wt. %, and 3 wt. %) on the degradation
behavior of PMMA denture bases was insignificant. The nanomechanical test results
of the PMMA and PMMA/TiO2 nanocomposites indicated that the hardness and modulus
in the nanoscale range improved due to TiO2 addition. At a 1200-nm penetration
depth, the modulus increased by 10%, 16%, and 29% and hardness increased by 18%,
24%, and 35% with the addition of 1 wt. %, 2 wt. %, and 3 wt. % TiO2,
respectively. Furthermore, the creep-recovery and relaxation behaviors of PMMA
were significantly improved due to the addition of TiO2. The creep strain
decreased from 1.41% to 1.06%, 0.66%, and 0.49% with the addition of 1 wt. %, 2
wt. %, and 3 wt. % TiO2, respectively. The relaxation test results showed that
the initial stress under 1% strain improved to 19.9, 21.2, and 22 MPa with the
addition of 1 wt. %, 2 wt. %, and 3 wt. % TiO2, respectively. The improvement in
the nanohardness, modulus, creep recovery, and relaxation behavior of PMMA due to
the addition of TiO2 nanoparticles indicated the role of the nanoparticles in
increasing the PMMA matrix stiffness by reducing its mobility and free volume.
TiO2 nanoparticles also improved the antimicrobial behavior of PMMA by
significantly reducing bacterial adherence with increasing TiO2 ratio.
PMID- 29954117
TI - The At Risk Child Clinic (ARCC): 3 Years of Health Activities in Support of the
Most Vulnerable Children in Beira, Mozambique.
AB - The concept of “children at risk” changes worldwide according to each
specific context. Africa has a large burden of overall risk factors related to
childhood health and development, most of which are of an infective or social
origin. The aim of this study was to report and analyze the volumes of activities
of fifteen At Risk Child Clinics (ARCCs) within the Beira District (Mozambique)
over a 3 year-period in order to define the health profile of children accessing
such health services. We retrospectively analyzed the data from all of the
children accessing one of the 15 Beira ARCCs from January 2015 to December 2017.
From this, 17,657 first consultations were registered. The motivations for
accessing the services were in order of relevance: HIV exposure (n. 12,300;
69.7%), other risk conditions (n. 2542; 14.4%), Moderate Acute Malnutrition (MAM)
(n. 1664; 9.4%), Severe Acute Malnutrition (SAM) (n. 772; 4.4%), and TB exposure
(n. 542; 3.1%). During the first consultations, 16,865 children were screened for
HIV (95.5%), and 7.89% tested HIV-positive. In our three years of experience, HIV
exposure was the main indication for children to access the ARCCs in Mozambique.
ARCCs could represent a strategic point to better understand health demands and
to monitor the quality of care provided to this vulnerable population group,
however significant effort is needed to improve the quality of the data
collection.
PMID- 29954118
TI - An alphaB-Crystallin Peptide Rescues Compartmentalization and Trafficking
Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson
Disease in the Caucasian Population.
AB - The H1069Q substitution is the most frequent mutation of the Cu transporter ATP7B
that causes Wilson disease in the Caucasian population. ATP7B localizes to the
Golgi complex in hepatocytes, but, in the presence of excessive Cu, it relocates
to the endo-lysosomal compartment to excrete Cu via bile canaliculi. In contrast,
ATP7B-H1069Q is strongly retained in the ER, does not reach the Golgi complex and
fails to move to the endo-lysosomal compartment in the presence of excessive Cu,
thus causing toxic Cu accumulation. We have previously shown that, in transfected
cells, the small heat-shock protein αB-crystallin is able to correct the
mislocalization of ATP7B-H1069Q and its trafficking in the presence of Cu
overload. Here, we first show that the α-crystallin domain of αB
crystallin mimics the effect of the full-length protein, whereas the N- and C
terminal domains have no such effect. Next, and most importantly, we demonstrate
that a twenty-residue peptide derived from the α-crystallin domain of
αB-crystallin fully rescues Golgi localization and the trafficking response
of ATP7B-H1069Q in the presence of Cu overload. In addition, we show that this
peptide interacts with the mutant transporter in the live cell. These results
open the way to attempt developing a pharmacologically active peptide to
specifically contrast the Wilson disease form caused by the ATP7B-H1069Q mutant.
PMID- 29954120
TI - Osteoblast Cell Response to Naturally Derived Calcium Phosphate-Based Materials.
AB - The demand of calcium phosphate bioceramics for biomedical applications is
constantly increasing. Efficient and cost-effective production can be achieved
using naturally derived materials. In this work, calcium phosphate powders,
obtained from dolomitic marble and Mytilus galloprovincialis seashells by a
previously reported and improved Rathje method were used to fabricate microporous
pellets through cold isostatic pressing followed by sintering at 1200 °C. The
interaction of the developed materials with MC3T3-E1 pre-osteoblasts was explored
in terms of cell adhesion, morphology, viability, proliferation, and
differentiation to evaluate their potential for bone regeneration. Results showed
appropriate cell adhesion and high viability without distinguishable differences
in the morphological features. Likewise, the pre-osteoblast proliferation
overtime on both naturally derived calcium phosphate materials showed a
statistically significant increase comparable to that of commercial
hydroxyapatite, used as reference material. Furthermore, evaluation of the
intracellular alkaline phosphatase activity and collagen synthesis and
deposition, used as markers of the osteogenic ability of these bioceramics,
revealed that all samples promoted pre-osteoblast differentiation. However, a
seashell-derived ceramic demonstrated a higher efficacy in inducing cell
differentiation, almost equivalent to that of the commercial hydroxyapatite.
Therefore, data obtained demonstrate that this naturally sourced calcium
phosphate material holds promise for applications in bone tissue regeneration.
PMID- 29954119
TI - Role of p53 in the Regulation of the Inflammatory Tumor Microenvironment and
Tumor Suppression.
AB - p53 has functional roles in tumor suppression as a guardian of the genome,
surveillant of oncogenic cell transformation, and as recently demonstrated, a
regulator of intracellular metabolism. Accumulating evidence has shown that the
tumor microenvironment, accompanied by inflammation and tissue remodeling, is
important for cancer proliferation, metastasis, and maintenance of cancer stem
cells (CSCs) that self-renew and generate the diverse cells comprising the tumor.
Furthermore, p53 has been demonstrated to inhibit inflammatory responses, and
functional loss of p53 causes excessive inflammatory reactions. Moreover, the
generation and maintenance of CSCs are supported by the inflammatory tumor
microenvironment. Considering that the functions of p53 inhibit reprogramming of
somatic cells to stem cells, p53 may have a major role in the inflammatory
microenvironment as a tumor suppressor. Here, we review our current understanding
of the mechanisms underlying the roles of p53 in regulation of the inflammatory
microenvironment, tumor microenvironment, and tumor suppression.
PMID- 29954121
TI - Cyclodextrin-Enabled Polymer Composites for Packaging ?.
AB - Cyclodextrin complexes of fragrances, antimicrobial agents, dyes, insecticides,
UV-filters can be incorporated into polymers (packaging films, trays, containers)
either to ensure the slow release or a homogeneous distribution of the complexed
substances. This way the propagation of microorganisms on surface of enwrapped
products is decelerated, or the product is made more attractive by slowly
released fragrances, protected against UV-light-induced deterioration, oxidation,
etc. Incorporating empty cyclodextrins into the packaging material an aroma
barrier packaging is produced, which decelerates the loss of the aroma from the
packaged food, prevents the penetration of undesired volatile pollutants from the
environment, like components of exhaust gases, cigarette smoke, and reduces the
migration of plasticizers, residual solvents and monomers, etc. Applying
cyclodextrins in active packaging allows to preserve the quality of food and
ensures a longer shelf-life for the packaged items.
PMID- 29954122
TI - Genome-Wide Identification and Expression Analyses of the Fibrillin Family Genes
Suggest Their Involvement in Photoprotection in Cucumber.
AB - Fibrillin (FBN) is a plastid lipid-associated protein found in photosynthetic
organisms from cyanobacteria to plants. In this study, 10 CsaFBN genes were
identified in genomic DNA sequences of cucumber (Chinese long and Gy14) through
database searches using the conserved domain of FBN and the 14 FBN genes of
Arabidopsis. Phylogenetic analysis of CsaFBN protein sequences showed that there
was no counterpart of Arabidopsis and rice FBN5 in the cucumber genome. FBN5 is
essential for growth in Arabidopsis and rice; its absence in cucumber may be
because of incomplete genome sequences or that another FBN carries out its
functions. Among the 10 CsaFBN genes, CsaFBN1 and CsaFBN9 were the most divergent
in terms of nucleotide sequences. Most of the CsaFBN genes were expressed in the
leaf, stem and fruit. CsaFBN4 showed the highest mRNA expression levels in
various tissues, followed by CsaFBN6, CsaFBN1 and CsaFBN9. High-light stress
combined with low temperature decreased photosynthetic efficiency and highly
induced transcript levels of CsaFBN1, CsaFBN6 and CsaFBN11, which decreased after
24 h treatment. Transcript levels of the other seven genes were changed only
slightly. This result suggests that CsaFBN1, CsaFBN6 and CsaFBN11 may be involved
in photoprotection under high-light conditions at low temperature.
PMID- 29954123
TI - Synergistic Effect of Bioactive Anticarcinogens from Soybean on Anti
Proliferative Activity in MDA-MB-231 and MCF-7 Human Breast Cancer Cells In
Vitro.
AB - Consumption of soybean products has been implicated in the prevention of breast
cancer. This study provides insights into the anti-proliferative activity of 12
anticarcinogens from soybean by single or two-way combination treatment against
MCF-7 and MDA-MB-231 human breast cancer cells. Results showed that genistein,
daidzein, glycitein, genistin and dainzin showed stronger anti-proliferative
activity against MCF-7 cells with EC50 values of 66.98 +/- 4.87 MUM, 130.14 +/-
2.10 MUM, 190.67 +/- 5.65 MUM, 72.82 +/- 2.66 MUM and 179.21 +/- 6.37 MUM,
respectively. There is a synergistic effect of combination treatment of genistin
plus daidzin in MCF-7 cells with combination index at inhibition of 50% (CI50) of
0.89 +/- 0.12. Genistein, glycitein, genistin and beta-sitosterol were
demonstrated to have a stronger anti-proliferative activity against MDA-MB-231
cells with EC50 values of 93.75 +/- 5.15 MUM, 142.67 +/- 5.88 MUM, 127.82 +/-
4.70 MUM and 196.28 +/- 4.45 MUM. The synergistic effect was observed in the
mixture of genistein plus genistin, genistein plus beta-sitosterol or beta
sitosterol plus genistin with CI50 values of 0.56 +/- 0.13, 0.54 +/- 0.20 and
0.45 +/- 0.12, respectively. These bioactive anticarcinogens were able to inhibit
invasion and migration of breast cancer cells and the combination treatments
enhanced the inhibitory effect. Regulation of PI3K/Akt/mTORpathway seems to be
the main mechanisms involved in the anticancer activity.
PMID- 29954125
TI - Electrode Modification and Optimization in Air-Cathode Single-Chamber Microbial
Fuel Cells.
AB - Due to the known problems of microbial fuel cells (MFCs), such as low electricity
generation performance and high cost of operation, we modified the electrode with
graphene and polyaniline (PANI) is a single-chamber air-cathode MFC and then
evaluated the effects of electrode modification on MFC electricity generation
performance. Carbon cloth electrodes (unmodified, CC; graphene-modified, G/CC;
and polyaniline-graphene-modified, PANI-G/CC) were prepared using the
impregnation method. Sulfonated cobalt phthalocyanine (CoPcS) was then introduced
as a cathode catalyst. The Co-PANI-G/CC cathode showed higher catalytic activity
toward oxygen reduction compared with other electrodes. The maximum power density
of the MFC with Co-PANI-G/CC cathode was 32.2 mW/m2, which was 1.8 and 6.1 times
higher than the value obtained with Co-G/CC and Co/CC cathodes, respectively.
This indicates a significant improvement in the electricity generation of single
chamber MFCs and provides a simple, effective cathode modification method.
Furthermore, we constructed single-chamber MFCs using the modified anode and
cathode and analyzed electricity generation and oxytetracycline (OTC) degradation
with different concentrations of OTC as the fuel. With increasing added OTC
concentration, the MFC performance in both electricity generation and OTC
degradation gradually decreased. However, when less than 50 mg/L OTC was added,
the 5-day degradation rate of OTC reached more than 90%. It is thus feasible to
process OTC-containing wastewater and produce electricity using single-chamber
MFCs, which provides a new concept for wastewater treatment.
PMID- 29954126
TI - High Dynamic Micro Vibrator with Integrated Optical Displacement Detector for In
Situ Self-Calibration of MEMS Inertial Sensors.
AB - The scale factor drifts and other long-term instability drifts of Micro-Electro
Mechanical System (MEMS) inertial sensors are the main contributors of the
position and orientation errors in high dynamic environments. In this paper, a
novel high dynamic micro vibrator, which could provide high acceleration and high
angular rate rotation with integrated optical displacement detector, is proposed.
Commercial MEMS inertial sensors, including 3-axis accelerometer and 6-axis
inertial measurement unit which is about 3 mm * 3 mm * 1 mm with 19 mg, could be
bonded on the vibration platform of the micro vibrator to perform in-situ during
the self-calibration procedure. The high dynamic micro vibrator is fabricated by
a fully-integrated MEMS process, including lead zirconate titanate (PZT) film
deposition, PZT and electrodes patterning, and structural ion etching. The
optical displacement detector, using vertical-cavity surface-emitting laser
(VCSEL) and photoelectric diodes (PD), is integrated on the top of the package to
measure the 6-DOF vibrating displacement with the detecting resolution of 150 nm
in the range of 500 μm. The maximum out-of-plane acceleration of the z-axis
vibrating platform loaded with commercial 3-axis accelerometer (H3LIS331DL)
achieves above 16 g and the maximum angular velocity achieves above 720°/s
when the driving voltage is +/-6 V.
PMID- 29954124
TI - Therapeutic Role of Green Tea Polyphenols in Improving Fertility: A Review.
AB - Sperm cells are highly sensitive to reactive oxygen species (ROS), which are
produced during cellular oxidation. In normal cell biology, ROS levels increase
with a decreasing antioxidant response, resulting in oxidative stress which
threatens sperm biology. Oxidative stress has numerous effects, including
increased apoptosis, reduced motion parameters, and reduced sperm integrity. In
this regard, green tea polyphenols (GrTPs) have been reported to possess
properties that may increase the quality of male and female gametes, mostly via
the capability of catechins to reduce ROS production. GrTPs have antioxidant
properties that improve major semen parameters, such as sperm concentration,
motility, morphology, DNA damage, fertility rate, and gamete quality. These
unique properties of green tea catechins could improve reproductive health and
represent an important study area. This exploratory review discusses the
therapeutic effects of GrTPs against infertility, their possible mechanisms of
action, and recommended supportive therapy for improving fertility in humans and
in animals.
PMID- 29954127
TI - Facile Synthesis of Novel CaIn2S4/ZnIn2S4 Composites with Efficient Performance
for Photocatalytic Reduction of Cr(VI) under Simulated Sunlight Irradiation.
AB - A series of novel and efficient heterostructured composites CaIn2S4/ZnIn2S4 have
been synthesized using a facile hydrothermal method. XRD patterns indicate the as
prepared catalysts are two-phase composites of cubic phase CaIn2S4 and hexagonal
phase ZnIn2S4. FESEM (field emission scanning electron microscope) images display
that the synthesized composites are composed of flower-like microspheres with
wide diameter distribution. UV-Vis diffuse reflectance spectra (DRS) show that
the optical absorption edges of the CaIn2S4/ZnIn2S4 composites shift toward
longer wavelengths with the increase of the CaIn2S4 component. The photocatalytic
activities of the as-synthesized composites are investigated by using the aqueous
phase Cr(VI) reduction under simulated sunlight irradiation. This is the first
report on the application of the CaIn2S4/ZnIn2S4 composites as stable and
efficient photocatalysts for the Cr(VI) reduction. The fabricated CaIn2S4/ZnIn2S4
composites possess higher photocatalytic performance in comparison with pristine
CaIn2S4 or ZnIn2S4. The CaIn2S4/ZnIn2S4 composite with a CaIn2S4 molar content of
30% exhibits the optimum photocatalytic activity. The primary reason for the
significantly enhanced photoreduction activity is proved to be the substantially
improved separation efficiency of photogenerated electrons/holes caused by
forming the CaIn2S4/ZnIn2S4 heterostructured composites. The efficient charge
separation can be evidenced by steady-state photoluminescence spectra (PLs) and
transient photocurrent response. Based on the charge transfer between CaIn2S4 and
ZnIn2S4, an enhancement mechanism of photocatalytic activity and stability for
the Cr(VI) reduction is proposed.
PMID- 29954128
TI - Upstream-Downstream Joint Carbon Reduction Strategies Based on Low-Carbon
Promotion.
AB - A differential game model is established to analyze the impact of emissions
reduction efforts and low-carbon product promotion on the reduction strategies of
low-carbon product manufacturers (subsequently referred to as manufacturers) and
the retailers of such products in a dynamic environment. Based on this model,
changes in emissions reduction efforts and promotional efforts are comparatively
analyzed under three scenarios (retailers bearing the promotional cost,
manufacturers bearing the promotional cost, and centralized decision-making). The
results are as follows: (1) the trajectory of carbon emissions reduction per
product unit is the highest when the supply chain is under centralized decision
making, followed by when manufacturers bear the promotional cost, and lastly when
retailers bear the cost; (2) when manufacturers bear the promotional cost, the
market demand, emissions reduction effort, and promotional effort are higher,
although the unit retail price is higher than when retailers bear the promotional
cost; and (3) under centralized decision-making, the unit retail price is the
lowest; however, sales volume, the emissions reduction effort, and the
promotional effort are all higher than those in the other scenarios.
PMID- 29954129
TI - Insights into the Role of PPARbeta/delta in NAFLD.
AB - Non-alcoholic fatty liver disease (NAFLD) is a major health issue in developed
countries. Although usually associated with obesity, NAFLD is also diagnosed in
individuals with low body mass index (BMI) values, especially in Asia. NAFLD can
progress from steatosis to non-alcoholic steatohepatitis (NASH), which is
characterized by liver damage and inflammation, leading to cirrhosis and
hepatocellular carcinoma (HCC). NAFLD development can be induced by lipid
metabolism alterations; imbalances of pro- and anti-inflammatory molecules; and
changes in various other factors, such as gut nutrient-derived signals and
adipokines. Obesity-related metabolic disorders may be improved by activation of
the nuclear receptor peroxisome proliferator-activated receptor
(PPAR)β/δ, which is involved in metabolic processes and other
functions. This review is focused on research findings related to
PPARβ/δ-mediated regulation of hepatic lipid and glucose metabolism
and NAFLD development. It also discusses the potential use of pharmacological
PPARβ/δ activation for NAFLD treatment.
PMID- 29954130
TI - Analysis of Metabolites in White Flowers of Magnolia Denudata Desr. and Violet
Flowers of Magnolia Liliiflora Desr.
AB - A total of seven phenolics and 44 metabolites was profiled in white flowers of
Magnolia denudata and violet flowers of Magnolia liliiflora using high
performance liquid chromatography (HPLC), electrospray ionization-mass
spectrometry (ESI-MS), and gas chromatography time-of-flight mass spectrometry
(GC-TOFMS). Seven phenylpropanoid compounds were identified in white flowers by
liquid chromatography mass spectrometry (LC-MS). An HPLC analysis showed that
phenylpropanoid accumulation in violet flowers was 1.48 times higher than that in
white flowers. Furthermore, superoxide dismutase (SOD)-like activity and 1,1
diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were determined to
investigate the antioxidant properties of secondary metabolites in different
flowers. Violet flowers showed higher SOD-like and DPPH activity than white
flowers. In addition, anti-inflammatory activity measured using a nitric oxide
assay was higher in violet flowers than in white flowers. Our results provide
valuable information on the relationship between primary and secondary
metabolites, and synergistic antioxidant and anti-inflammatory properties derived
from phenolic compounds in different colored flowers.
PMID- 29954132
TI - Effects of Parental Migration on Life Satisfaction and Academic Achievement of
Left-Behind Children in Rural China-A Case Study in Hubei Province.
AB - In the rural areas of China, there is a high occurrence of parental migration,
wherein adults are flushed into urban areas to search for employment
opportunities, leading to millions of left-behind children (LBC) in rural China.
LBC attracts more attention from the social community and Chinese government.
Here, we compared the life satisfaction and academic achievement of left-behind
children (LBC) and non-left-behind children (NLBC) in rural regions that send out
migrant labor in Hubei province, central China. We investigated 1031 LBC and 992
NLBC students in grades 4 to 9 in ten elementary and four middle schools, using a
structured questionnaire including sociodemographic characteristics, life
satisfaction, and academic achievement scores. The results showed that LBC have a
lower life satisfaction and lower academic achievement than NLBC (p < 0.01).
Meanwhile, as the child’s age at separation from parents decreased, their
life satisfaction decreased. Additionally, correlations were observed between
life satisfaction and academic achievement scores in LBC (p = 0.004) as well as
in NLBC (p = 0.064). Collectively, these findings provide novel insights into a
comprehensive understanding of LBC and suggest that the life satisfaction levels
of LBC should be improved in rural China.
PMID- 29954131
TI - Intake of Dietary One-Carbon Metabolism-Related B Vitamins and the Risk of
Esophageal Cancer: A Dose-Response Meta-Analysis.
AB - Several B vitamins are essential in the one-carbon metabolism pathway, which is
central to DNA methylation, synthesis, and repair. Moreover, an imbalance in this
pathway has been linked to certain types of cancers. Here, we performed a meta
analysis in order to investigate the relationship between the intake of four
dietary one-carbon metabolism-related B vitamins (B2, B6, folate, and B12) and
the risk of esophageal cancer (EC). We searched PubMed, Web of Science, and
Embase for relevant studies published through 1 March 2018. The odds ratio (OR)
with 95% confidence interval (CI) for the highest versus the lowest level of each
dietary B vitamin was then calculated. From 21 articles reporting 26 studies
including 6404 EC cases and 504,550 controls, we found an inverse correlation
between the consumption of vitamin B6 and folate and the risk of EC; this
association was specific to the US, Europe, and Australia, but was not found in
Asia. A dose-response analysis revealed that each 100 μg/day increase in
folate intake reduced the risk of EC by 12%. Moreover, each 1 mg/day increase in
vitamin B6 intake decreased the risk of EC by 16%. Surprisingly, we found that
each 1 μg/day increase in vitamin B12 intake increased the risk of esophageal
adenocarcinoma by 2%, particularly in the US and Europe, suggesting both
geographic and histological differences. Together, our results suggest that an
increased intake of one-carbon metabolism-related B vitamins may protect against
EC, with the exception of vitamin B12, which should be consumed in moderation.
PMID- 29954134
TI - Sensitivity Enhancement in Surface Plasmon Resonance Biochemical Sensor Based on
Transition Metal Dichalcogenides/Graphene Heterostructure.
AB - In this work, a surface plasmon resonance (SPR) biosensor based on two
dimensional transition metal dichalcogenides (TMDCs) is proposed to improve the
biosensor’s sensitivity. In this sensor, different kinds of two-dimensional
TMDCs are coated on both surfaces of metal film. By optimizing the structural
parameters, the angular sensitivity can reach as high as 315.5 Deg/RIU with 7
layers WS2 and 36 nm Al thin film, which is 3.3 times of the conventional
structure based on single Al thin film. We also obtain maximum phase sensitivity
(3.85 × 106 Deg/RIU) with bilayer WS2 and 35 nm Al thin film. The phase
sensitivity can be further improved by employing Ag and removing air layer. The
proposed configuration is of great potential for biochemical sensing.
PMID- 29954135
TI - Real-Time Curvature Detection of a Flexible Needle with a Bevel Tip.
AB - As one of the major methods for the diagnosis and treatment of cancers in their
early stages, the percutaneous puncture technique has bright prospect in biopsy,
ablation, proximity radiotherapy, and drug delivery. Recent years, researchers
found the flexible needle cannot realize feedback control during the puncture
surgeries only by path planning. To solve this problem, the flexible needle is
tried to achieve real-time detection in this paper. Compared with previous
methods, the strain gauges glued on the needle surface rather than the medical
imaging techniques is used to collect the information to reconstruct the needle
curve, which is benefit to integrate the whole system and obtain a more simple
and accurate closed-loop control. This paper presented the math model of curve
fitting and analyzed the causes of curve fitting errors. To verify the
feasibility of this method, an experiment setup was built. Results from the
experiments validated the solution in this paper to be effective.
PMID- 29954133
TI - CFTR Deletion Confers Mitochondrial Dysfunction and Disrupts Lipid Homeostasis in
Intestinal Epithelial Cells.
AB - BACKGROUND: Cystic Fibrosis (CF) is a genetic disease in which the intestine
exhibits oxidative and inflammatory markers. As mitochondria are the central
source and the main target of reactive oxygen species, we hypothesized that
cystic fibrosis transmembrane conductance regulator (CFTR) defect leads to the
disruption of cellular lipid homeostasis, which contributes to mitochondrial
dysfunction. METHODS: Mitochondrial functions and lipid metabolism were
investigated in Caco-2/15 cells with CFTR knockout (CFTR-/-) engineered by the
zinc finger nuclease technique. Experiments were performed under basal conditions
and after the addition of the pro-oxidant iron-ascorbate (Fe/Asc) complex.
RESULTS: Mitochondria of intestinal cells with CFTR-/-, spontaneously showed an
altered redox homeostasis characterised by a significant decrease in the
expression of PPARα and nuclear factor like 2. Consistent with these
observations, 8-oxoguanine-DNA glycosylase, responsible for repair of ROS-induced
DNA lesion, was weakly expressed in CFTR-/- cells. Moreover, disturbed fatty acid
β-oxidation process was evidenced by the reduced expression of CPT1 and acyl
CoA dehydrogenase long-chain in CFTR-/- cells. The decline of mitochondrial
cytochrome c and B-cell lymphoma 2 expression pointing to magnified apoptosis.
Mitochondrial respiration was also affected as demonstrated by the low expression
of respiratory oxidative phosphorylation (OXPHOS) complexes and a high adenosine
diphosphate/adenosine triphosphate ratio. In contrast, the FAS and ACC enzymes
were markedly increased, thereby indicating lipogenesis stimulation. This was
associated with an augmented secretion of lipids, lipoproteins and
apolipoproteins in CFTR-/- cells. The addition of Fe/Asc worsened while butylated
hydroxy toluene partially improved these processes. CONCLUSIONS: CFTR silencing
results in lipid homeostasis disruption and mitochondrial dysfunction in
intestinal epithelial cells. Further investigation is needed to elucidate the
mechanisms underlying the marked abnormalities in response to CFTR deletion.
PMID- 29954137
TI - High Performance Ultrathin MoO3/Ag Transparent Electrode and Its Application in
Semitransparent Organic Solar Cells.
AB - In this paper, we demonstrate high performance ultrathin silver (Ag) transparent
electrodes with a thin MoO3 nucleation layer based on the thermal evaporation
method. The MoO3/Ag transparent electrodes fabricated at different deposition
rates were compared systematically on aspects of the transmission spectrum,
surface resistance, and surface morphology. Our study indicates that with the
presence of the MoO3 nucleation layer, an Ag film of only 7 nm thick can achieve
percolation and the film is porous instead of forming isolated islands. In
addition, the increase of the deposition rate can yield obvious improvement of
the surface morphology of the Ag film. Specifically, with the help of a 1 nm
thick MoO3 nucleation layer, the Ag film of 9 nm thick realized under the
deposition rate of 0.7 nm/s has a surface resistance of about 20 ohm/sq and an
average transmittance in the visible light range reaching 74.22%. Such a high
performance of transmittance is superior to the reported results in the
literature, which inevitably suffer obvious drop in the long wavelength range.
Next, we applied the ultrathin MoO3/Ag transparent electrode in organic solar
cells. The optimized semitransparent organic solar cell displays a power
conversion efficiency of 2.76% and an average transmittance in the visible range
of 38% when light is incident from the Ag electrode side.
PMID- 29954136
TI - Exposure to Environmental Contaminants and Lung Function in Adolescents-Is There
a Link?
AB - Dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated
dibenzofurans (PCDF)), polychlorinated biphenyls (PCBs), and brominated flame
retardants (BDEs) are well known toxic environmental contaminants. Their possible
role in the incidence of respiratory disease is not yet well understood. Previous
studies showed a negative effect on lung function in relation to prenatal and
lactational dioxin exposure in pre-pubertal children. Effects of BDE exposure on
the lung function have not previously been evaluated. As part of a longitudinal
cohort study, the effects of perinatal dioxin (PCDD/F) exposure and serum PCDD/F,
dl-PCB, and BDE levels on lung function in adolescents were assessed using
spirometry, a body box, and diffusion measurements. Thirty-three children (born
between 1986 and 1991) consented to the current follow-up study. Prenatal,
lactational, and current dioxin, PCB, and BDE concentrations were determined
using GC-MS. No relationship was seen between prenatal and lactational dioxin
exposure, nor with current PCB body burden, and lung function. Indications of
increasing airway obstruction were seen in relation to increasing current BDE
exposure. This is a novel finding and certainly warrants further research.
PMID- 29954138
TI - A One-Pot Biginelli Synthesis and Characterization of Novel Dihydropyrimidinone
Derivatives Containing Piperazine/Morpholine Moiety.
AB - Enaminones, 4-methyl-1-[4-(piperazin/morpholin-1-yl) phenyl] pent-2-en-1-one (IIa
b) were synthesized by refluxing 1-[4-(piperazin/morpholin-1-yl) phenyl] ethan-1
one (Ia-b) with dimethylformamide dimethylacetal (DMF-DMA) without any solvent.
The three dimensional structure of enaminone (IIb) containing morpholine moiety
was confirmed by single crystal X-ray crystallography. Finally, the
dihydropyrimidinone derivatives (1-20) were obtained by reacting enaminones (IIa
b) with urea and different substituted benzaldehydes in the presence of glacial
acetic acid. Dihydropyrimidinone derivatives containing piperazine/morpholine
moiety were synthesized in a good yield by means of simple and efficient method.
PMID- 29954139
TI - Human Dental Pulp Stem Cells Exhibit Different Biological Behaviours in Response
to Commercial Bleaching Products.
AB - The purpose of this study was to evaluate the diffusion capacity and the
biological effects of different bleaching products on human dental pulp stem
cells (hDPSCs). The bleaching gel was applied for 90, 30 or 15 min to
enamel/dentine discs that adapted in an artificial chamber. The diffusion of
hydrogen peroxide (HP) was analysed by fluorometry and the diffusion products
were applied to hDPSCs. Cell viability, cell migration and cell morphology assays
were performed using the eluates of diffusion products. Finally, cell apoptosis
and the expression of mesenchymal stem cell markers were analysed by flow
cytometry. Statistical analysis was performed using analysis of variance and
Kruskal-Wallis or Mann-Whitney tests (α < 0.05). Significant reductions of
approximately 95% in cell viability were observed for the 3 × 15 min groups
(p < 0.001), while 1 × 30 min of PerfectBleach and 1 × 90 min of
PolaNight resulted in reductions of 50% and 60% in cell viability, respectively
(p < 0.001). Similar results were obtained in the migration assay. Moreover, the
3 × 15 min group was associated with cell morphology alterations and
reductions of >70% in cell live. Finally, hDPSCs maintained their mesenchymal
phenotype in all conditions. Similar concentrations of carbamide peroxide (CP)
and HP in different commercial products exhibited different biological effects on
hDPSCs.
PMID- 29954140
TI - Thermodynamic, Structural and Thermoelectric Properties of AgSbTe2 Thick Films
Developed by Melt Spinning.
AB - Cubic AgSbTe2 compound is a metastable phase within Ag2Te-Sb2Te3 pseudo-binary
phase diagram and theoretically rapid cooling molten elements to room temperature
may be an effective way to obtain it. In this work, thick films composed of 5-10
nm fine grains were developed by a melt spinning technique. The formation
mechanism of the nanostructure and its influences on the thermoelectric
properties have been studied and correlated. Differential scanning calorimetry
(DSC) analysis shows that the as-prepared films exhibit distinct thermodynamic
properties when prepared under different cooling rates and doping element. A
small amount of Se doping is effectively capable of inhibiting the emergence of
the Ag2Te impurity and optimizing the electrical transport properties. All films
have positive large Seebeck coefficient, but rather small positive or negative
Hall coefficient, indicating a multicarrier nature of transport consisting of
both holes and electrons. A power factor of ~1.3 was achieved at 500 K for Se
doped film for its excellent electrical conductivities. This result confirms that
a combination of Se doping and melting spinning technique is an effective way to
obtain high phase-pure AgSbTe2 compound and reveal its intrinsic transport
properties routinely masked by impurities in sintering or slow-cooling bulk
samples.
PMID- 29954141
TI - Neurocognitive, Autonomic, and Mood Effects of Adderall: A Pilot Study of Healthy
College Students.
AB - Prescription stimulant medications are considered a safe and long-term effective
treatment for Attention Deficit Hyperactivity Disorder (ADHD). Studies support
that stimulants enhance attention, memory, self-regulation and executive function
in individuals with ADHD. Recent research, however, has found that many college
students without ADHD report misusing prescription stimulants, primarily to
enhance their cognitive abilities. This practice raises the question whether
stimulants actually enhance cognitive functioning in college students without
ADHD. We investigated the effects of mixed-salts amphetamine (i.e., Adderall, 30
mg) on cognitive, autonomic and emotional functioning in a pilot sample of
healthy college students without ADHD (n = 13), using a double-blind, placebo
controlled, within-subjects design. The present study was the first to explore
cognitive effects in conjunction with mood, autonomic effects, and self
perceptions of cognitive enhancement. Results revealed that Adderall had minimal,
but mixed, effects on cognitive processes relevant to neurocognitive enhancement
(small effects), and substantial effects on autonomic responses, subjective drug
experiences, and positive states of activated emotion (large effects). Overall,
the present findings indicate dissociation between the effects of Adderall on
activation and neurocognition, and more importantly, contrary to common belief,
Adderall had little impact on neurocognitive performance in healthy college
students. Given the pilot design of the study and small sample size these
findings should be interpreted cautiously. The results have implications for
future studies and the education of healthy college students and adults who
commonly use Adderall to enhance neurocognition.
PMID- 29954142
TI - Detection of Aflatoxigenic and Atoxigenic Mexican Aspergillus Strains by the
Dichlorvos-Ammonia (DV-AM) Method.
AB - The dichlorvos-ammonia (DV-AM) method is a sensitive method for distinguishing
aflatoxigenic fungi by detecting red (positive) colonies. In this study, the DV
AM method was applied for the isolation of aflatoxigenic and atoxigenic fungi
from soil samples from a maize field in Mexico. In the first screening, we
obtained two isolates from two soil subsamples of 20 independent samples and, in
the second screening, we obtained two isolates from one subsample of these.
Morphological and phylogenic analyses of the two isolates (MEX-A19-13, MEX-A19
2nd-5) indicated that they were Aspergillus flavus located in the A. flavus
clade. Chemical analyses demonstrated that one isolate could produce B-type
aflatoxins, while the other produced no aflatoxins. These results demonstrate
that the DV-AM method is useful for the isolation of both aflatoxigenic and
atoxigenic Aspergilli.
PMID- 29954143
TI - Nanosynthesis of Silver-Calcium Glycerophosphate: Promising Association against
Oral Pathogens.
AB - Nanobiomaterials combining remineralization and antimicrobial abilities would
bring important benefits to control dental caries. This study aimed to produce
nanocompounds containing calcium glycerophosphate (CaGP) and silver nanoparticles
(AgNP) by varying the reducing agent of silver nitrate (sodium borohydride (B) or
sodium citrate (C)), the concentration of silver (1% or 10%), and the CaGP forms
(nano or commercial), and analyze its characterization and antimicrobial activity
against ATCC Candida albicans (10231) and Streptococcus mutans (25175) by the
microdilution method. Controls of AgNP were produced and silver ions (Ag+) were
quantified in all of the samples. X-ray diffraction, UV-Vis, and scanning
electron microscopy (SEM) analysis demonstrated AgNP associated with CaGP. Ag+
ions were considerably higher in AgCaGP/C. C. albicans was susceptible to
nanocompounds produced with both reducing agents, regardless of Ag concentration
and CaGP form, being Ag10%CaGP-N/C the most effective compound (19.5-39.0
µg Ag mL−1). While for S. mutans, the effectiveness was observed only
for AgCaGP reduced by citrate, also presenting Ag10%CaGP-N the highest
effectiveness (156.2-312.5 µg Ag mL−1). Notably, CaGP enhanced the
silver antimicrobial potential in about two- and eight-fold against C. albicans
and S. mutans when compared with the AgNP controls (from 7.8 to 3.9 and from 250
to 31.2 µg Ag mL−1, respectively). The synthesis that was used in
this study promoted the formation of AgNP associated with CaGP, and although the
use of sodium borohydride (B) resulted in a pronounced reduction of Ag+, the
composite AgCaGP/B was less effective against the microorganisms that were
tested.
PMID- 29954144
TI - Preliminary RNA-Seq Analysis of Long Non-Coding RNAs Expressed in Human Term
Placenta.
AB - Development of particular structures and proper functioning of the placenta are
under the influence of sophisticated pathways, controlled by the expression of
substantial genes that are additionally regulated by long non-coding RNAs
(lncRNAs). To date, the expression profile of lncRNA in human term placenta has
not been fully established. This study was conducted to characterize the lncRNA
expression profile in human term placenta and to verify whether there are
differences in the transcriptomic profile between the sex of the fetus and
pregnancy multiplicity. RNA-Seq data were used to profile, quantify, and classify
lncRNAs in human term placenta. The applied methodology enabled detection of the
expression of 4463 isoforms from 2899 annotated lncRNA loci, plus 990 putative
lncRNA transcripts from 607 intergenic regions. Those placentally expressed
lncRNAs displayed features such as shorter transcript length, longer exon length,
fewer exons, and lower expression levels compared to messenger RNAs (mRNAs).
Among all placental transcripts, 175,268 were classified as mRNAs and 15,819 as
lncRNAs, and 56,727 variants were discovered within unannotated regions. Five
differentially expressed lncRNAs (HAND2-AS1, XIST, RP1-97J1.2, AC010084.1,
TTTY15) were identified by a sex-bias comparison. Splicing events were detected
within 37 genes and 4 lncRNA loci. Functional analysis of cis-related potential
targets for lncRNAs identified 2021 enriched genes. It is presumed that the
obtained data will expand the current knowledge of lncRNAs in placenta and human
non-coding catalogs, making them more contemporary and specific.
PMID- 29954145
TI - In-Vitro Activity of Silybin and Related Flavonolignans against Leishmania
infantum and L. donovani.
AB - Flavonolignans from the seeds of the milk thistle (Silybum marianum) have been
extensively used in folk medicine for centuries. Confirmation of their properties
as hepatoprotective, antioxidant and anticancer has been obtained using
standardized extracts and purified flavonolignans. Information on their potential
effect on Leishmania is very scarce. We have investigated the effect of
silymarin, silybin and related flavonolignans on the multiplication of
promastigotes in vitro and ex vivo on intracellular amastigotes of L. infantum
(Li) and L. donovani (Ld), causative agents of human and canine visceral
leishmaniasis (VL). In addition, the potential synergistic effect of the most
active molecule and well-established antileishmanial drugs against promastigotes
was explored. Dehydroisosilybin A elicited the highest inhibition against Ld and
Li promastigotes with an approximate IC50 of 90.23 µM. This molecule showed
a moderate synergism with amphotericin B (AmB) but not with SbIII or paromomycin,
although it was ineffective against amastigotes. Antileishmanial activity on
intracellular amastigotes of the two diastereoisomers of dehydrosilybin (10
µM) was comparable to that elicited by 0.1 µM AmB. Antiproliferative
activity and safety of flavonolignans suggest the interest of exploring their
potential value in combination therapy against VL.
PMID- 29954146
TI - RES-Q-Trace: A Mobile CEAS-Based Demonstrator for Multi-Component Trace Gas
Detection in the MIR.
AB - Sensitive trace gas detection plays an important role in current challenges
occurring in areas such as industrial process control and environmental
monitoring. In particular, for medical breath analysis and for the detection of
illegal substances, e.g., drugs and explosives, a selective and sensitive
detection of trace gases in real-time is required. We report on a compact and
transportable multi-component system (RES-Q-Trace) for molecular trace gas
detection based on cavity-enhanced techniques in the mid-infrared (MIR). The RES
Q-Trace system can operate four independent continuous wave quantum or interband
cascade lasers each combined with an optical cavity. Twice the method of off-axis
cavity-enhanced absorption spectroscopy (OA-CEAS) was used, twice the method of
optical feedback cavity-enhanced absorption spectroscopy (OF-CEAS), respectively.
Multi-functional software has been implemented (i) for the general system
control; (ii) to drive the four different laser sources and (iii) to analyze the
detector signals for concentration determination of several molecular species.
For the validation of the versatility and the performance of the RES-Q-Trace
instrument the species NO, N2O, CH4, C2H4 and C3H6O, with relevance in the fields
of breath gas analysis and the detection of explosives have been monitored in the
MIR with detection limits at atmospheric pressure in the ppb and ppt range.
PMID- 29954147
TI - Narrow Band Filter at 1550 nm Based on Quasi-One-Dimensional Photonic Crystal
with a Mirror-Symmetric Heterostructure.
AB - In this paper, we present a high-efficiency narrow band filter (NBF) based on
quasi-one-dimensional photonic crystal (PC) with a mirror symmetric
heterostructure. Similarly to the Fabry-Perot-like resonance cavity, the
alternately-arranged dielectric layers on both sides act as the high reflectance
and the junction layers used as the defect mode of the quasi-one-dimensional PC,
which can be designed as a NBF. The critical conditions for the narrow pass band
with high transmittance are demonstrated and analyzed by simulation and
experiment. The simulation results indicate that the transmission peak of the
quasi-one-dimensional PC-based NBF is up to 95.99% at the telecommunication
wavelength of 1550 nm, which agrees well with the experiment. Furthermore, the
influences of the periodicity and thickness of dielectric layers on the
transmission properties of the PC-based NBF also have been studied numerically.
Due to its favorable properties of PC-based NBF, it is can be found to have many
potential applications, such as detection, sensing, and communication.
PMID- 29954148
TI - Behaviour-Based Husbandry-A Holistic Approach to the Management of Abnormal
Repetitive Behaviors.
AB - The field of zoo animal welfare science has developed significantly over recent
years. However despite this progress in terms of scientific research, globally,
zoo animals still face many welfare challenges. Recently, animal welfare
frameworks such as the five domains or five needs have been developed and
suggested to improve the welfare of zoo animals, but without practical guidance,
such tools may remain abstract from the daily experience of zoo animals.
Similarly specific practical strategies such as those for enrichment development
exist, but their lack of holistic integration with other aspects of animal
husbandry and behavioral medicine means that overall, good zoo animal welfare may
still be lacking. This paper outlines some of the barriers to implementing
improved zoo animal welfare in practice, and proposes a new strategy for the
development of behavioral husbandry routines focused on the management and
mitigation of abnormal repetitive behaviors. Focusing on enhancing zoo animal
welfare by integrating aspects of ecology, ethology and clinical animal behavior
into a practical and comprehensive approach to behavior-based husbandry.
PMID- 29954149
TI - APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype
Phenotype Correlation.
AB - APC and MUTYH genes are mutated in 70-90% and 10-30% of familial adenomatous
polyposis cases (FAP) respectively. An association between mutation localization
and FAP clinical phenotype is reported. The aims of this study were to determine
APC and MUTYH mutational status in a small cohort of FAP patients and to evaluate
the genotype-phenotype correlation in mutated patients. Here, we report the
identification of a novel APC germline mutation, c.510_511insA. Overall,
mutational analysis showed pathogenic mutations in 6/10 patients: 5/10 in APC and
1/10 in MUTYH. Additionally, we found three variants of unknown significance in
MUTYH gene that showed no evidence of possible splicing defects by in silico
analysis. Molecular analysis was also extended to family members of mutated
patients. A genotype-phenotype correlation was observed for colonic signs whereas
a variation of disease onset age was revealed for the same mutation. Moreover, we
found an intrafamilial variability of FAP onset age. Regarding extracolonic
manifestations, the development of desmoid tumors was related to surgery and not
to mutation position, while a genotype-phenotype correspondence was observed for
the onset of thyroid or gastric cancer. These findings can be useful in
association to clinical data for early surveillance and suitable treatment of FAP
patients.
PMID- 29954150
TI - DynSig: Modelling Dynamic Signaling Alterations along Gene Pathways for
Identifying Differential Pathways.
AB - Although a number of methods have been proposed for identifying differentially
expressed pathways (DEPs), few efforts consider the dynamic components of pathway
networks, i.e., gene links. We here propose a signaling dynamics detection method
for identification of DEPs, DynSig, which detects the molecular signaling changes
in cancerous cells along pathway topology. Specifically, DynSig relies on gene
links, instead of gene nodes, in pathways, and models the dynamic behavior of
pathways based on Markov chain model (MCM). By incorporating the dynamics of
molecular signaling, DynSig allows for an in-depth characterization of pathway
activity. To identify DEPs, a novel statistic of activity alteration of pathways
was formulated as an overall signaling perturbation score between sample classes.
Experimental results on both simulation and real-world datasets demonstrate the
effectiveness and efficiency of the proposed method in identifying differential
pathways.
PMID- 29954151
TI - Cognitive Bias in Zoo Animals: An Optimistic Outlook for Welfare Assessment.
AB - Cognitive bias testing measures how emotional states can affect cognitive
processes, often described using the “glass half-full/half-empty”
paradigm. Classical or operant conditioning is used to measure responses to
ambiguous cues, and it has been reported across many species and contexts that an
animal’s cognitive bias can be directly linked to welfare state, e.g.,
those in better welfare make more optimistic judgements. Cognitive bias testing
has only recently been applied to animals and represents a key milestone in
welfare science: it is currently one of the only accurate methods available to
measure welfare. The tests have been conducted on many farm, laboratory, and
companion animal species, but have only been carried out in zoo settings a
handful of times. The aims of this review are to evaluate the feasibility of
cognitive bias testing in zoos and its potential as a tool for studying zoo
animal welfare. The few existing zoo cognitive bias studies are reviewed, as well
as those conducted on similar, non-domesticated species. This work is then used
to discuss how tests could be successfully designed and executed in zoo settings,
which types of tests are most appropriate in different contexts, and how the data
could be used to improve animal welfare. The review closely examines the many
variables are present in the zoo which cannot be controlled as in other settings,
termed here the Zoo Environment (ZE) Variables. It is recommended that tests are
developed after consideration of each of the ZE Variables, and through strong
collaboration between zookeepers, managers, and academic institutions. There is
much unexplored potential of cognitive bias testing in the zoo setting, not least
its use in investigating animal welfare in zoos. It is hoped that this review
will stimulate increased interest in this topic from zoo managers, scientists,
and industry regulators alike.
PMID- 29954152
TI - Fabrication and Characterization of Finite-Size DNA 2D Ring and 3D Buckyball
Structures.
AB - In order to incorporate functionalization into synthesized DNA nanostructures,
enhance their production yield, and utilize them in various applications, it is
necessary to study their physical stabilities and dynamic characteristics.
Although simulation-based analysis used for DNA nanostructures provides important
clues to explain their self-assembly mechanism, structural function, and
intrinsic dynamic characteristics, few studies have focused on the simulation of
DNA supramolecular structures due to the structural complexity and high
computational cost. Here, we demonstrated the feasibility of using normal mode
analysis for relatively complex DNA structures with larger molecular weights,
i.e., finite-size DNA 2D rings and 3D buckyball structures. The normal mode
analysis was carried out using the mass-weighted chemical elastic network model
(MWCENM) and the symmetry-constrained elastic network model (SCENM), both of
which are precise and efficient modeling methodologies. MWCENM considers both the
weight of the nucleotides and the chemical bonds between atoms, and SCENM can
obtain mode shapes of a whole structure by using only a repeated unit and its
connectivity with neighboring units. Our results show the intrinsic vibrational
features of DNA ring structures, which experience inner/outer circle and bridge
motions, as well as DNA buckyball structures having overall breathing and local
breathing motions. These could be used as the fundamental basis for designing and
constructing more complicated DNA nanostructures.
PMID- 29954153
TI - Wide-Band Color Imagery Restoration for RGB-NIR Single Sensor Images.
AB - Multi-spectral RGB-NIR sensors have become ubiquitous in recent years. These
sensors allow the visible and near-infrared spectral bands of a given scene to be
captured at the same time. With such cameras, the acquired imagery has a
compromised RGB color representation due to near-infrared bands (700-1100 nm)
cross-talking with the visible bands (400-700 nm). This paper proposes two deep
learning-based architectures to recover the full RGB color images, thus removing
the NIR information from the visible bands. The proposed approaches directly
restore the high-resolution RGB image by means of convolutional neural networks.
They are evaluated with several outdoor images; both architectures reach a
similar performance when evaluated in different scenarios and using different
similarity metrics. Both of them improve the state of the art approaches.
PMID- 29954154
TI - Assessing Novel Drugs and Radiation Technology in the Chemoradiation of
Oropharyngeal Cancer.
AB - Integrating immunotherapy, proton therapy and biological dose escalation into the
definitive chemoradiation of oropharyngeal cancer poses several challenges.
Reliable and reproducible data must be obtained in a timely fashion. However,
despite recent international radiotherapy contouring guidelines, controversy
persists as to the applicability of such guidelines to all cases. Similarly, a
lack of consensus exists concerning both the definition of the organ at risk for
oral mucositis and the most appropriate endpoint to measure for this critical
toxicity. Finally, the correlation between early markers of efficacy such as
complete response on PET CT following treatment and subsequent survival needs
elucidation for biological subsets of oropharyngeal cancer.
PMID- 29954155
TI - Methods for the Real-World Evaluation of Fall Detection Technology: A Scoping
Review.
AB - Falls in older adults present a major growing healthcare challenge and reliable
detection of falls is crucial to minimise their consequences. The majority of
development and testing has used laboratory simulations. As simulations do not
cover the wide range of real-world scenarios performance is poor when retested
using real-world data. There has been a move from the use of simulated falls
towards the use of real-world data. This review aims to assess the current
methods for real-world evaluation of fall detection systems, identify their
limitations and propose improved robust methods of evaluation. Twenty-two
articles met the inclusion criteria and were assessed with regard to the
composition of the datasets, data processing methods and the measures of
performance. Real-world tests of fall detection technology are inherently
challenging and it is clear the field is in its infancy. Most studies used small
datasets and studies differed on how to quantify the ability to avoid false
alarms and how to identify non-falls, a concept which is virtually impossible to
define and standardise. To increase robustness and make results comparable,
larger standardised datasets are needed containing data from a range of
participant groups. Measures that depend on the definition and identification of
non-falls should be avoided. Sensitivity, precision and F-measure emerged as the
most suitable robust measures for evaluating the real-world performance of fall
detection systems.
PMID- 29954156
TI - Evaluating Disparities in Elderly Community Care Resources: Using a Geographic
Accessibility and Inequality Index.
AB - This study evaluated geographic accessibility and utilized assessment indices to
investigate disparities in elderly community care resource distribution. The data
were derived from Taiwanese governmental data in 2017, including 3,148,283
elderly individuals (age 65+), 7681 villages, and 1941 community care centers. To
identify disparities in geographic accessibility, we compared the efficacy of six
measurements and proposed a composite index to identify levels of resource
inequality from the Gini coefficient and “median-mean” skewness. Low
village-level correlation (0.038) indicated inconsistencies between the demand
populations and community care center distribution. Method M6 (calculated
accessibility of nearest distance-decay accounting for population of villages,
supplier loading, and elderly walkability) was identified as the most
comprehensive disparity measurement. Community care policy assessment requires a
comprehensive and weighted calculation process, including the elderly walkability
distance-decay factor, demand population, and supplier loading. Three steps were
suggested for elderly policy planning and improvement in future.
PMID- 29954157
TI - Elevated Proangiogenic Markers are Associated with Vascular Complications within
Ghanaian Sickle Cell Disease Patients.
AB - : Sickle cell disease (SCD) is an inherited blood disorder that can result in
vasculopathy and end organ damage. Angiogenesis has been implicated as a key
contributing factor to vascular mediated tissue injury in SCD. The relative
plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular
endothelial growth factor (VEGF) greatly influence angiogenesis. Dysregulation of
these growth factors, leading to a pro-angiogenic state in SCD patients, has been
documented in the developed world but there is very little data in Africa. There
is the need, therefore, for studies in Ghanaian SCD patients. The aim of this
study was to assess plasma levels of Ang-1, Ang-2, and VEGF in homozygous (HbSS)
SCD patients with or without complications and healthy controls (HbAA) in Ghana.
The study was a case-control study involving 544 participants: 396 HbSS SCD
patients and 148 HbAA healthy controls. The study was conducted at the Center for
Clinical Genetics (Sickle Cell Clinic) and Accra Area Blood Centre for National
Blood transfusion at the Korle-Bu Teaching Hospital, Accra, Ghana. The plasma
levels of Ang-1, Ang-2, and VEGF of study participants were measured with a
double sandwich enzyme-linked immunosorbent assay (ELISA) technique. Complete
blood count (CBC) was measured with an autoanalyser. The mean plasma Ang-1, Ang
2, and VEGF were significantly higher in HbSS SCD patients with or without
complications than healthy controls (p < 0.001). The Ang-2/Ang-1 ratio was
significantly lower in the controls than the HbSS patients (p < 0.001). The Ang
2/Ang-1 ratio was higher in the HbSS patients with leg ulcers as compared with
patients with other complications and healthy controls (p < 0.001). There were
higher leucocyte counts in HbSS patients than healthy controls. Overall, there
was elevated plasma levels of Ang-1, Ang-2, and VEGF in SCD patients. The higher
Ang-2/Ang-1 plasma levels in patients with leg ulcers suggests a possible ongoing
angiogenesis and response to inflammatory stimuli. The study provides a first
report on plasma levels of angiopoietin-1, angiopoietin-2, and vascular
endothelial growth factors in homozygous sickle cell disease patients in Ghana.
PMID- 29954159
TI - Surface specializations of planarian gastrodermal cells as revealed by staining
with ruthenium red.
AB - Regional differences of the surface of planarian gastrodermal cells are
emphasized by staining with ruthenium red (RR). It is proposed that such
differences reflect functional diversity of the luminal, lateral, and basal
surfaces of the cells. The luminal surface is coated with a uniform layer of the
RR-positive substance, which penetrates into the intercellular space at the
intermediate junction. The septate junction situated just beneath the
intermediate junction shows a permeability barrier to the RR tracer. At the
basolateral surface, however, RR stains the septate junction in which the
electron density of individual septa is enhanced remarkably. The gastrodermal
cells are delineated entirely with RR-positive substance passing freely through
the gap junction fuses into the outer leaflets of adjacent plasma membranes. The
irregularly dilated intercellular space at nonjunctional appositions includes a
slight deposit of RR-positive substance which attaches to the plasma membrane.
The basal surface is underlined by the continuous basal lamina, which consists of
the lamina lucida and the lamina densa. The lamina densa has a conspicuous
affinity for RR. The lamina lucida is characterized by irregular deposits of RR
positive substance, some of which concentrates on the hemidesmosomal portions.
Treatment with the enzyme hyaluronidase prior to staining with RR abolishes the
staining of the basal lamina. As a result, the material of the lamina densa
appears flocculent.
PMID- 29954160
TI - Study of atresia in the ovary during the annual reproductive cycle and nesting
cycle of the pied myna.
AB - Atretic follicles of the ovary of the Indian pied myna (Sturnus contra contra)
were studied in birds collected each month throughout the year. Histological
examination included histochemical techniques for 3beta-hydroxy-steroid
dehydrogenase (3beta-HSDH) and for lipids. Atretic follicles were mainly of two
types: nonbursting (lipoidal and cystic) and bursting (Types I-VI). Nonbursting
atresia was observed in the smaller follicles (< 500 MUm in diameter), whereas
larger follicles (> 500 MUm in diameter, viz., small developing, large
developing, and yolky follicles) showed exclusively a bursting type of atresia.
Sudanophilic lipid was found in both types (lipoidal and cystic) of nonbursting
atresia, but was present only in early stages of bursting atresia. Activity of
3beta-HSDH was absent in nonbursting atresia, but present in early stage of
bursting atresia. Nonbursting atresia was common throughout the year and higher
in frequency than the bursting type. Bursting atresia was common during March
through May and attained its peak level during the nesting cycle.
PMID- 29954161
TI - Structure, function and evolution of the reproductive system in females of Hebrus
pusillus and H. ruficeps (hemiptera, gerromorpha, hebridae).
AB - Females of Hebrus pusillus and H. ruficeps have two ovaries of five telotrophic
ovarioles each, two lateral oviducts, a common an intricate sperm storage and
delivery system, the gynatrial complex, and a short, tubular ovipositor. The
skeletomusculature of this system is fully described in both species and its
functions (summarized in Figs. 55-66) reconstructed from study of living bugs,
dissections, whole mounts and serial sections. To mate, a male H. pusillus jumps
on the back of a female, induces her to lower her ovipositor, and, within 12 min
(at 18-24 degrees C), introduces the endosoma of his phallus up its shaft and
fills his seminal duct with sperm. The female draws this into her gynatrial sac
at the end of copulation and transfers it into her spermatheca in about 30 min
(both sperm and spermatheca are longer than the female's body). A single, large
egg passes from an ovariole into the vagina where its apex is temporarily lodged
in a fertilization chamber. Spermatozoa are drawn from or swim out of the
spermatheca into a grooved fecundation canal in the roof of the vagina and
forward to the micropyle of the egg. After fertilization, the egg enters the base
of the ovipositor and is deposited. The gynatrial complex of female, semiaquatic
bugs probably evolved to accommodate the fertilization of the proportionately
larger eggs of a lineage of bugs ancestral to Gerromorpha that was being selected
for small body size and was then modified to increase the role of the female in
controlling fertilization of eggs.
PMID- 29954162
TI - The fine structure of the dorsal column nucleus and the nucleus of bischoff of
the python (Python reticulatus).
AB - Three types of neuronal perikaryal profiles were identified in the dorsal column
nucleus and the nucleus of Bischoff of the python (Python reticulatus). Type I
neuronal profiles are large (diameters 12-20 MUm) with a deeply indented uncleus.
The cisterns of rough endoplasmic reticulum (rER) are mostly randomly dispersed.
Axosomatic synapses are few. Type II neuronal profiles (9-11 MUm) have a smooth,
round, or slightly oval nucleus. Several small stacks of rER are present. Type
III neuronal profiles (8-10 MUm) have little cytoplasm. The nuclear margin is
irregular but not deeply infolded. The rER usually consists of a single long
perinuclear ribosome-studded cistern. Two types of astrocytic profiles have been
identified. Both types contain abundant filaments. Type I astrocytes are large
cells, and the nucleus is very irregular in shape. Type II astrocytes are smaller
and are found among the myelinated axons in the dorsal funiculus. Two classes of
axon terminals have been identified. One class contains round synaptic vesicles
(R profiles) and the other flattened vesicles (F profiles). Some R profiles are
small (SR profiles), others are large (LR profiles). Some R profiles also contain
a few large, dense-cored vesicles. The R and F profiles establish axodendritic
and axoaxonal synapses, some of which are located in the synaptic glomeruli and
others in the extraglomerular neuropil. In most of the axoaxonal synapses, the
presynaptic element is an F profile and the post synaptic element an LR profile.
Occasionally, LR profiles are presynaptic to F profiles. The findings in the
python are compared with those of the dorsal column nuclei of the rat, cat, and
monkey.
PMID- 29954163
TI - The fine structure of the nephronic tubule of the mudskipper Periophthalmus
koelreuteri (Pallas).
AB - Ultrastructural examination of the head kidney of Periophthalmus koelreuteri
(Pallas) (Teleostei, Gobiidae) revealed that the nephronic tubule cells are bound
by tight junctions and desmosomes with little intercellular space. The first
proximal segment (PI) consists of low columnar cells with well developed brush
borders, indented nuclei, and numerous apical endocytic vesicles and lysosomes. A
second cell type possessing clusters of apical cilia and lacking brush border and
lysosomes is occasionally found between PI cells. The second proximal segment
(PII) is formed of high columnar cells with brush border, regular spherical
nuclei and numerous mitochondria located between well developed infoldings of the
basal membrane. Single ciliary structures protrude into the lumen from PI and PII
cells. The distal segment is lined by low columnar epithelium with few
microvilli, regular spherical nuclei, numerous scattered mitochondria, and
microbodies. The collecting tubule cells are cuboidal with few euchromatic
nuclei, some mitochondria, and secondary lysosomes.
PMID- 29954158
TI - Obesity and Aging in the Drosophila Model.
AB - Being overweight increases the risk of many metabolic disorders, but how it
affects lifespan is not completely clear. Not all obese people become ill, and
the exact mechanism that turns excessive fat storage into a health-threatening
state remains unknown. Drosophila melanogaster has served as an excellent model
for many diseases, including obesity, diabetes, and hyperglycemia-associated
disorders, such as cardiomyopathy or nephropathy. Here, we review the connections
between fat storage and aging in different types of fly obesity. Whereas obesity
induced by high-fat or high-sugar diet is associated with hyperglycemia,
cardiomyopathy, and in some cases, shortening of lifespan, there are also
examples in which obesity correlates with longevity. Transgenic lines with
downregulations of the insulin/insulin-like growth factor (IIS) and target of
rapamycin (TOR) signaling pathways, flies reared under dietary restriction, and
even certain longevity selection lines are obese, yet long-lived. The mechanisms
that underlie the differential lifespans in distinct types of obesity remain to
be elucidated, but fat turnover, inflammatory pathways, and dysregulations of
glucose metabolism may play key roles. Altogether, Drosophila is an excellent
model to study the physiology of adiposity in both health and disease.
PMID- 29954164
TI - The fine structure and development of calcified skeletal elements in the body
wall of holothurian echinoderms.
AB - The calcareous ossicles and iron-rich calcified granules in the integument of sea
cucumbers (Echinodermata: Holothuroida) have been examined by light and electron
microscopy. Most ossicles are perforated, platelike structures that measure 100
500 MUm long and consist of magnesium-rich calcite. The formation of ossicles
occurs within multinucleated syncytia of sclerocytes that are situated in the
dermal layer of the body wall. Sclerocytes possess fairly large numbers of
mitochondria and are characteristically enveloped by an external lamina. Each
ossicle arises as a minute rodlike spicule that branches and develops into a
fenestrated skeletal element. When viewed by SEM, fully developed ossicles appear
non-crystalline. Following decoration with synthetically grown calcite seeds,
however, each ossicle reveals an ordered array of crystallites that seem to be
aligned perpendicular to the ossicle's original plane of growth. Examinations of
sectioned ossicles indicate that the mineral phase in each skeletal element lacks
a well developed matrix of EDTA-insoluble organic substances. Ossicles first
arise in the ciliated, lecithotrophic larvae of Eupentacta quinquesimita at about
1 week postfertilization. Two-week-old specimens adopt an epibenthic existence
and subsequently become enveloped by imbricated ossicles that are secreted by
sclerocytes resembling those found in adults. In molpadiid holothurians, the
adult body wall contains numerous reddish-brown granules that are chiefly
composed of iron-rich subunits. The dermal granules differ from calcitic ossicles
in developing extracellularly in association with finely filamentous material.
PMID- 29954165
TI - Synthesis of the mesoglea by ectoderm and endoderm in reassembled hydra.
AB - The structure and synthesis of the mesoglea was investigated in "reassembled"
hydra-hydra regenerating from ectoderm and endoderm previously isolated from each
other and then recombined. During tissue isolation and reassembly the mesoglea
remains attached to the endoderm. It is observed to be quite elastic and
resilient. The mesoglea disappears by 6-8 hr after reassembly, having apparently
been digested by endoderm. "New" mesoglea is undergoing synthesis by 12 hr after
reassembly. It trilaminar appearance at this time suggests an origin from both
epithelia. Interepithelial contact, by cell processes of epithelial cells, is
reestablished within the mesoglea between 24 and 48 hr after reassembly. Mesoglea
appears normal 48 hr after reassembly. Autoradiographic experiments, performed
during the reassembly manipulations, conclusively demonstrate that the mesoglea
originates from both epithelia. Mesoglea precursors, amino acids, are
incorporated within the mesoglea about 5-6 hr after initial acquisition by
epithelia, but subsequent turnover of these amino acids is slow.
PMID- 29954166
TI - The morphology of Idiocranium russeli (amphibia: Gymnophiona), with comments on
miniaturization through heterochrony.
PMID- 29954167
TI - The pharyngeal jaw apparatus of labrid fishes: A functional morphological
perspective.
AB - Among the acanthopterygian fishes, the Labridae possess the most highly
integrated and specialized pharyngeal jaw apparatus. The integrated feature
involves many osteological components and aspects of muscle form, architecture,
composition, and function. The upper jaw articulates by means of a true
diarthrosis with the pharyngeal process of the parasphenoid, whereas the lower
jaw has established physical contact with the cleithrum. Complex muscle fusions
have contributed significantly in the development of a double muscle sling
operating the lower jaw. The original levator externus 4 fuses with the central
head of the obliquus posterior, whereas the original levator posterior combines
with the lateral head of the obliquus posterior as well as with the adductor
branchialis 5. During the masticatory cycle, both upper and lower jaws undergo
complex movement orbits resulting in shearing and crushing functions. Shearing
occurs as the forward moving upper jaw collides with the dorsally held lower jaw.
Crushing is effected by an extreme posterodorsal movement of the lower jaw
against the retracted upper jaw, thereby establishing full occlusion of the
teeth. The specialized morphological and functional design of the labrid
pharyngeal jaw apparatus is similar to that found in cichlids. In sharp contrast
to primitive acanthopterygian fishes, the Labridae and Cichlidae exhibit a
spectacular morphological diversity that parallels their ecological
diversification. Our combined functional and historical analysis has established
a correlation between the complex integration of the pharyngeal jaw apparatus and
morphological and ecological diversity in the Labridae and Cichlidae.
PMID- 29954168
TI - The fate and role of openings formed in the mesentery of bullfrog tadpoles, with
reference to the contour of mesothelial cells.
AB - Using morphological techniques, histological changes of the mesentery were
observed during the development of the bullfrog, Rana catesbeiana. The tadpoles
of this species had many openings all over the mesentery from the duodenum
through the large intestine. Most of the openings were elliptical and less than 3
* 2 mm in size. The openings became remarkably decreased in size and number with
rapid narrowing of the mesentery occurring during the period of metamorphic
climax, and had almost completely disappeared by the end of metamorphosis.
Appearance and disappearance of the openings were closely correlated with the
changes in the dimensions of the mesentery. Furthermore, in parallel with these
changes in the openings, a noticeable alteration occurred in the shape of the
mesothelial cells of the mesentery. In tadpoles having no mesenteric openings,
the mesothelial cells had a polygonal contour, which became transformed once the
openings were formed in the mesentery. The shapes of the transformed cells were
classified into two types, one having many radiating cell processes and the other
a very slender and spindle-shaped contour. Both types of cells eventually became
transformed into a definitive type of cell exhibiting a roundish polygonal
contour by the end of metamorphosis. From these findings it was concluded that
the growing mesentery might, of necessity, give rise to the openings and
transformation of the mesothelial cells to enable rapid lengthening and
shortining of the intestinal tract to occur during the postembryonic development
of anuran amphibians.
PMID- 29954169
TI - Covalent Modification of Biomolecules through Maleimide-Based Labeling
Strategies.
AB - Since their first use in bioconjugation more than 50 years ago, maleimides have
become privileged chemical partners for the site-selective modification of
proteins via thio-Michael addition of biothiols and, to a lesser extent, via
Diels-Alder (DA) reactions with biocompatible dienes. Prominent examples include
immunotoxins and marketed maleimide-based antibody-drug conjugates (ADCs) such as
Adcetris, which are used in cancer therapies. Among the key factors in the
success of these groups is the availability of several maleimides that can be N
functionalized by fluorophores, affinity tags, spin labels, and pharmacophores,
as well as their unique reactivities in terms of selectivity and kinetics.
However, maleimide conjugate reactions have long been considered irreversible,
and only recently have systematic studies regarding their reversibility and
stability toward hydrolysis been reported. This review provides an overview of
the diverse applications for maleimides in bioconjugation, highlighting their
strengths and weaknesses, which are being overcome by recent strategies. Finally,
the fluorescence quenching ability of maleimides was leveraged for the
preparation of fluorogenic probes, which are mainly used for the specific
detection of thiol analytes. A summary of the reported structures, their
photophysical features, and their relative efficiencies is discussed in the last
part of the review.
PMID- 29954170
TI - Electronic Structure and Rydberg-Core Interactions in Hydroxycarbene and
Methylhydroxycarbene.
AB - Vertical and adiabatic excitation energies and oscillator strengths for valence
and Rydberg states of hydroxycarbene (HCOH) and methylhydroxycarbene (CH3COH) are
reported. The electronic properties were computed with equation-of-motion coupled
cluster methods with single and double substitution methods (EOM-CCSD) and the
aug-cc-pVTZ basis set. The states' characters were analyzed by plotting natural
transition orbitals (NTOs). The calculations demonstrate that the shape, size,
and energy of each Rydberg orbital are affected to varying degrees by their
interaction with the ion core. Likewise, the corresponding quantum defects
reflect the Rydberg electron-ion core interactions. The results reported herein,
combined with previously reported calculations of the photoelectron spectrum of
HCOH, should help in designing strategies for state-selective detection of
hydroxycarbenes via ionization.
PMID- 29954171
TI - High-Performance Filaments from Fractionated Alginate by Polyvalent Cross
Linking: A Theoretical and Practical Approach.
AB - A series of alginate fractions with significant differences in molecular weight
and uronic acid compositions were produced by consecutive fractionation and
converted to thin and strong cross-linked polymer filaments via extrusion into
calcium, aluminum, or polyaluminum (PolyAl) polyvalent solutions followed by
drawing and drying. Models were elaborated to relate the alginate uronic acid
composition to the tensile performance in both the wet gel filament and the dry
filament states. The wet gel model was compared to the theory of the
unidirectional elongation of charged polyelectrolyte gels based on the classical
rubber elasticity of dilated polymer networks, extended to include the
contributions of non-Gaussian chain extensions and the effect of electrostatic
interactions. The theory of equilibrium swelling pressure was applied to describe
the observed shrinkage of the alginate gels following immersion in a polyvalent
solution. Congruent with the theoretical model of charged gels, the tensile
performance of the gel filaments prepared from CaCl2 depended on the
compositional ratio of guluronic acid dyads in the alginate fraction multiplied
by the alginate concentration, while the tensile behavior of wet gel filaments
prepared by AlCl3 instead resembled that of elastic solid materials and depended
only on the alginate concentration. The dry filament tensile properties were
greatly dependent on the preparation conditions, particularly the ratio of stress
to alginate concentration and the nature of the ions present during filament
drawing. The PolyAl solution effectively caused shrinkage of alginate to a strong
extent, and the resulting filaments behaved as highly stiff materials able to
withstand stresses of approximately 500 MPa and having elastic moduli as high as
28 GPa.
PMID- 29954172
TI - Shear-Induced Changes of Electronic Properties in Gallium Nitride.
AB - We show that sliding on the surface of GaN can permanently change the surface
band structure, resulting in an increased degree of band bending by more than 0.5
eV. We hypothesize that shear and contact stresses introduce vacancies that cause
a spatially variant band bending. Band bending is observed by shifts and
broadening of core-level binding energies toward lower values in X-ray
photoelectron spectroscopy. The extent of band bending is controlled by humidity,
number of sliding cycles and applied load, presenting opportunities for scalable
tuning of the degree of band bending on a GaN surface. Scanning transmission
electron microscopy revealed that the epitaxy of GaN was preserved up to the
surface with regions of defects near the surface. The hypothesized mechanism of
band bending is shear-induced defect generation, which has been shown to affect
the surface states. The ability to introduce band bending at the GaN surface is
promising for applications in photovoltaics, photocatalysis, gas sensing, and
photoelectrochemical processes.
PMID- 29954173
TI - Automated Separation of Uranium and Plutonium from Environmental Swipe Samples
for Multiple Collector Inductively Coupled Plasma Mass Spectrometry.
AB - A fully automated method for the separation of low-concentration uranium from
plutonium in environmental swipe samples has been developed. The offline
chromatography system features renewable 1 mL Eichrom TEVA and UTEVA column
generation from bulk resin slurry. Discrete fractions of the separated actinides
are delivered into user defined vials for future analysis. Clean room background
levels were achieved outside of a cleanroom environment with this method.
Purification of uranium and plutonium from various sample matrixes and at various
concentrations was successful. Major and minor isotope ratios for both elements
were measured via multiple collector inductively coupled plasma mass spectrometry
and were in good agreement with certified reference values. Validation of the
separation method was conducted on archived environmental samples and agreed with
values previously reported using standard column chemistry.
PMID- 29954174
TI - Rapid Analysis of Illegal Cationic Dyes in Foods and Surface Waters Using High
Temperature Direct Analysis in Real Time High-Resolution Mass Spectrometry.
AB - A high temperature desorption (HTD) direct analysis in real time-high-resolution
mass spectrometric (DART-HRMS) method was developed for the rapid analysis of
four banned cationic dyes. Rhodamine B is used to dye foods, while malachite
green, crystal violet, and methylene blue are added to fishponds as
antimicrobials. A simple induced phase separation extraction was used to pretreat
samples. The DART-HRMS method employed two temperature steps, i.e., 200 degrees
C for drying, purification, and enrichment of sample solution and 500 degrees C
for thermal desorption and ionization of analytes. The calibration curves of dyes
in the range of 50-2000 ng/mL were linear using deuterated malachite green as an
internal standard. The LODs vary for all analytes between 0.1 and 30 ppb
depending on the matrix and experimental conditions. Through analyses of real
samples, two chili powders and one chili oil were found to be contaminated by
rhodamine B. The concentrations were comparable with those found by an HPLC-MS/MS
method.
PMID- 29954175
TI - Chronic Heat Stress Damages Small Intestinal Epithelium Cells Associated with the
Adenosine 5'-Monophosphate-Activated Protein Kinase Pathway in Broilers.
AB - Heat-stressed broilers usually reduce their feed intake, leading to energy
imbalance and disturbing the homeostasis in the small intestine. This study was
aimed to explore heat-stress-mediated physiological features that may be ascribed
to impairments in the intestinal tract of broilers. The results revealed that
heat exposure increased the activities of trypsin and Na+/K+-ATPase, while it
decreased the activities of amylase, lipase, and maltase as well as the
proliferating cell nuclear antigen cells in the jejunum after 14 days of heat
exposure. Meanwhile, heat stress upregulated the mRNA expressions of AMPKalpha1,
LKB1, and HIF-1alpha and protein expressions of p-AMPKalphaThr172 and p
LKB1Thr189 in the small intestine after 7 or 14 days of heat exposure. In
conclusion, chronic heat exposure impeded the development of digestive organs,
disordered the activities of intestinal digestive enzymes, and impaired the
intestinal epithelial cells by increasing the cell apoptosis and declining cell
proliferation, which might be correlated with the adenosine 5'-monophosphate
activated protein kinase signaling pathway. Additionally, heat stress upregulated
the gene expression of HIF-1alpha, which indicated that heat stress may disturb
the homeostasis in the intestine.
PMID- 29954176
TI - Second-Sphere Effects on Methane Hydroxylation in Cu-Zeolites.
AB - Two [Cu2O]2+ cores have been identified as the active sites of low temperature
methane hydroxylation in the zeolite Cu-MOR. These cores have similar geometric
and electronic structures, yet different reactivity with CH4: one reacts with a
much lower activation enthalpy. In the present study, we couple experimental
reactivity and spectroscopy studies to DFT calculations to arrive at structural
models of the Cu-MOR active sites. We find that the more reactive core is located
in a constricted region of the zeolite lattice. This leads to close van der Waals
contact between the substrate and the zeolite lattice in the vicinity of the
active site. The resulting enthalpy of substrate adsorption drives the subsequent
H atom abstraction step-a manifestation of the "nest" effect seen in hydrocarbon
cracking on acid zeolites. This defines a mechanism to tune the reactivity of
metal active sites in microporous materials.
PMID- 29954177
TI - Simplest MOF Units for Effective Photodriven Hydrogen Evolution Reaction.
AB - Metal-organic frameworks (MOFs) combining the merits of both organic and
inorganic functional building structures are fundamentally important and can meet
the requirement of vast scientific and technological applications. Intrigued from
the fact that transition metals (TMs) are widely embedded in the carbon sp2
network or strongly interact with a bare graphene edge, the single transition
metal atom may work as a linker to connect carbon chains to build
nanoarchitectures. A new MOF building structure, [Metal-Carbon-(Benzene) i-Chain]
n ring abbreviated as [M-CB iC] n (M = Ti, V, and Cr), with increasing carbon
chain length i (= 0, 1, 2, ...), was proposed as carbon chains CB iC connected by
a single transition metal atom M to form a ring structure with multiedges n (= 2
6), based on advanced computational methods. They are thermodynamically stable
and chemically and physically versatile with ring shape, electronic structures,
optical response, as well as hydrogen adsorption energy that vary by changing the
length of the carbon chain, the edge number of rings, or the type of connecting
metal atoms. The optical response to incoming light of [M-CB iC] n rings can be
adjustable to cover the entire visible solar spectrum range and exhibit a red
shift by either increasing the edge number n or filling the d bands in connecting
transition metals. In combination with their ideal adsorption energy of hydrogen
atoms, |Delta GH*|, the proposed [M-CB iC] n building structure is attractive for
photocatalytic or photoelectrochemical hydrogen evolution applications when they
are extended in space to build up 1D, 2D, and 3D MOF frameworks.
PMID- 29954178
TI - Highly Ambiphilic Room Temperature Stable Six-Membered Cyclic
(Alkyl)(amino)carbenes.
AB - Cyclic (alkyl)(amino)carbenes with a six-membered backbone were prepared.
Compared to their five-membered analogues, they feature increased % Vbur and
enhanced donor and acceptor properties, as evidenced by the observed n -> pi*
transition trailing into the visible region. The high ambiphilic character even
allows for the intramolecular insertion of the carbene into an unactivated C(sp3)
H bond. When used as ligands, they outcompete the five-membered analogues in the
palladium-mediated alpha-arylation of ketones with aryl chlorides.
PMID- 29954179
TI - Constraining Carbon Nanothread Structures by Experimental and Calculated Nuclear
Magnetic Resonance Spectra.
AB - A one-dimensional (1D) sp3 carbon nanomaterial with high lateral packing order,
known as carbon nanothreads, has recently been synthesized by slowly compressing
and decompressing crystalline solid benzene at high pressure. The atomic
structure of an individual nanothread has not yet been determined experimentally.
We have calculated the 13C nuclear magnetic resonance (NMR) chemical shifts,
chemical shielding tensors, and anisotropies of several axially ordered and
disordered partially saturated and fully saturated nanothreads within density
functional theory and systematically compared the results with experimental solid
state NMR data to assist in identifying the structures of the synthesized
nanothreads. In the fully saturated threads, every carbon atom in each progenitor
benzene molecule has bonded to a neighboring molecule (i.e., 6 bonds per
molecule, a so-called "degree-6" nanothread), while the partially saturated
threads examined retain a single double bond per benzene ring ("degree-4"). The
most-parsimonious theoretical fit to the experimental 1D solid-state NMR
spectrum, constrained by the measured chemical shift anisotropies and key
features of two-dimensional NMR spectra, suggests a certain combination of degree
4 and degree-6 nanothreads as plausible components of this 1D sp3 carbon
nanomaterial, with intriguing hints of a [4 + 2] cycloaddition pathway toward
nanothread formation from benzene columns in the progenitor molecular crystal,
based on the presence of nanothreads IV-7, IV-8, and square polymer in the
minimal fit.
PMID- 29954181
TI - Revisited Chaos in a Diffusion-Precipitation-Redissolution Liesegang System.
AB - Co(OH)2 Liesegang periodic precipitation systems exhibit oscillations in the
number of bands due to band redissolution in high NH4OH concentration. We revisit
the problem previously considered (Nasreddine and Sultan, J. Phys. Chem. A 1999,
103, 2934-2940) by rigorously refining the experiments and the Chaos analysis.
Chaos is established in this diffusion-precipitation-redissolution system, as is
evident from the refined outputs of the Chaos analysis tools. A brief account of
possible applications of Chaos in Liesegang systems is presented.
PMID- 29954180
TI - Paradigm Shift for Radical S-Adenosyl-l-methionine Reactions: The Organometallic
Intermediate Omega Is Central to Catalysis.
AB - Radical S-adenosyl-l-methionine (SAM) enzymes comprise a vast superfamily
catalyzing diverse reactions essential to all life through homolytic SAM cleavage
to liberate the highly reactive 5'-deoxyadenosyl radical (5'-dAdo.). Our recent
observation of a catalytically competent organometallic intermediate Omega that
forms during reaction of the radical SAM (RS) enzyme pyruvate formate-lyase
activating-enzyme (PFL-AE) was therefore quite surprising, and led to the
question of its broad relevance in the superfamily. We now show that Omega in PFL
AE forms as an intermediate under a variety of mixing order conditions,
suggesting it is central to catalysis in this enzyme. We further demonstrate that
Omega forms in a suite of RS enzymes chosen to span the totality of superfamily
reaction types, implicating Omega as essential in catalysis across the RS
superfamily. Finally, EPR and electron nuclear double resonance spectroscopy
establish that Omega involves an Fe-C5' bond between 5'-dAdo. and the [4Fe-4S]
cluster. An analogous organometallic bond is found in the well-known
adenosylcobalamin (coenzyme B12) cofactor used to initiate radical reactions via
a 5'-dAdo. intermediate. Liberation of a reactive 5'-dAdo. intermediate via
homolytic metal-carbon bond cleavage thus appears to be similar for Omega and
coenzyme B12. However, coenzyme B12 is involved in enzymes catalyzing only a
small number (~12) of distinct reactions, whereas the RS superfamily has more
than 100 000 distinct sequences and over 80 reaction types characterized to date.
The appearance of Omega across the RS superfamily therefore dramatically enlarges
the sphere of bio-organometallic chemistry in Nature.
PMID- 29954182
TI - Gelatin/Maltodextrin Water-in-Water (W/W) Emulsions for the Preparation of Cross
Linked Enzyme-Loaded Microgels.
AB - Cross-linked gelatin microgels were formed in gelatin-in-maltodextrin water-in
water (W/W) emulsions and evaluated as carriers of the enzyme beta-galactosidase
(beta-Gal). The phase behavior of aqueous gelatin/maltodextrin mixtures was
studied in detail, focusing on the multiphase region of the phase diagram that is
constituted by three equilibrium phases: two immiscible aqueous phases plus one
solid phase. The solid phase was analyzed by Raman spectroscopy, and water-in
water emulsions were formed within the multiphase region. Gelation of the
dispersed gelatin droplets was induced by cooling and cross-linking with genipin,
which is a natural cross-linking reagent of low toxicity, leading to the
formation of gelatin microgel particles. These microgels were studied as delivery
vehicles for the enzyme lactase, used as a model active component. Various
incorporation methods of the enzyme were tested, to achieve highest encapsulation
yield and activity recovery. Microgel particles, loaded with the enzyme, can be
freeze-dried, and the enzyme remained active after a complete cycle of freeze
drying and rehydration. The stability of the enzyme at 37 degrees C under
gastric and neutral pH conditions was tested and led to the conclusion that the
cross-linked microgels could be suitable for use in food-industry, where beta-Gal
carriers are of interest for hydrolyzing lactose in milk products.
PMID- 29954184
TI - Algorithms used in telemonitoring programmes for patients with chronic heart
failure: A systematic review.
AB - INTRODUCTION: Non-invasive telemonitoring programmes detecting deterioration of
heart failure are increasingly used in heart failure care. AIM: The aim of this
study was to compare different monitoring algorithms used in non-invasive
telemonitoring programmes for patients with chronic heart failure. METHODS: We
performed a systematic literature review in MEDLINE (PubMed) and Embase to
identify published reports on non-invasive telemonitoring programmes in patients
with heart failure aged over 18 years. RESULTS: Out of 99 studies included in the
study, 20 (20%) studies described the algorithm used for monitoring worsening
heart failure or algorithms used for titration of heart failure medication. Most
frequently used biometric measurements were bodyweight (96%), blood pressure
(85%) and heart rate (61%). Algorithms to detect worsening heart failure were
based on daily changes in bodyweight in 20 (100%) studies and/or blood pressure
in 12 (60%) studies. In 12 (60%) studies patients were contacted by telephone in
the case of measurements outside thresholds. CONCLUSION: Only one in five studies
on telemonitoring in chronic heart failure reported the algorithm that was used
to detect worsening heart failure. Standardised description of the telemonitoring
algorithm can expedite the identification of key components in telemonitoring
algorithms that allow accurate prediction of worsening heart failure.
PMID- 29954183
TI - Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis. A Randomized
Controlled Trial.
AB - RATIONALE: We examined whether increased rifampin doses could shorten standard
therapy for tuberculosis without increased toxicity. OBJECTIVES: To assess the
differences across three daily oral doses of rifampin in change in elimination
rate of Mycobacterium tuberculosis in sputum and frequency of rifampin-related
adverse events. METHODS: We conducted a blinded, randomized, controlled phase 2
clinical trial of 180 adults with new smear-positive pulmonary tuberculosis,
susceptible to isoniazid and rifampin. We randomized 1:1:1 to rifampin at 10, 15,
and 20 mg/kg/d during the intensive phase. We report the primary efficacy and
safety endpoints: change in elimination rate of M. tuberculosis log10 colony
forming units and frequency of grade 2 or higher rifampin-related adverse events.
We report efficacy by treatment arm and by primary (area under the plasma
concentration-time curve [AUC]/minimum inhibitory concentration [MIC]) and
secondary (AUC) pharmacokinetic exposure. MEASUREMENTS AND MAIN RESULTS: Each 5
mg/kg/d increase in rifampin dose resulted in differences of -0.011 (95%
confidence interval, -0.025 to +0.002; P = 0.230) and -0.022 (95% confidence
interval, -0.046 to -0.002; P = 0.022) log10 cfu/ml/d in the modified intention
to-treat and per-protocol analyses, respectively. The elimination rate in the per
protocol population increased significantly with rifampin AUC0-6 (P = 0.011) but
not with AUC0-6/MIC99.9 (P = 0.053). Grade 2 or higher rifampin-related adverse
events occurred with similar frequency across the three treatment arms: 26, 31,
and 23 participants (43.3%, 51.7%, and 38.3%, respectively) had at least one
event (P = 0.7092) up to 4 weeks after the intensive phase. Treatment failed or
disease recurred in 11 participants (6.1%). CONCLUSIONS: Our findings of more
rapid sputum sterilization and similar toxicity with higher rifampin doses
support investigation of increased rifampin doses to shorten tuberculosis
treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 01408914) .
PMID- 29954185
TI - Spotlight on avian pathology: red mite, a serious emergent problem in layer hens.
AB - Dermanyssus gallinae, the poultry red mite, is currently the most important
ectoparasite of the egg laying industry worldwide with an expanding global
prevalence. As a blood-feeder, it causes anaemia and severe welfare issues to the
hens and it is a major cause of economic losses. It is also a vector for
Salmonella species, avian influenza and potentially for other vector-borne
pathogens. Paradoxically, there is a notable lack of funding for research into
poultry red mite and an urgent need for effective and safe control strategies,
sustainable therapies, prophylactics and integrated pest management.
PMID- 29954186
TI - Meeting report: 30th International Conference on Antiviral Research, in Atlanta,
GA, USA.
AB - The 30th International Conference on Antiviral Research was held in Atlanta, GA,
USA, from 21 to 25 May 2017. Each year, the International Society for Antiviral
Research (ISAR) presents three major awards, this year to Mike Sofia (Elion
award), David Chu (Holy award) and Maaike Everts (Prusoff award). Also this year,
the inaugural ISAR Women in Science award lecture was presented by Priscilla
Yang. For several years, International Conference on Antiviral Research (ICAR)
has included at least one Keynote lecture, this year there were four. Although
there are accounts of only these eight lectures, they reflect the diversity that
is characteristic of ICAR - employment (academia, industry, public health), type
of research (virus biology, potential antiviral targets, antiviral drugs,
research organisation) and a range of viruses. For example, the viruses included
were hepatitis C virus and hepatitis B virus (Mike Sofia), HIV and hepatitis B
virus (David Chu), multiple antiviral projects (Maaike Everts), dengue (Priscilla
Yang), rhinovirus C (Ann Palmenberg), polio (Mark Pallansch), HIV (Eric Hunter)
and Zika virus (Pei-Yong Shi). This report ends with my personal comments giving
examples in which this diversity can bring benefits. The 31st ICAR will be in
Porto, Portugal, 11-15 June 2018.
PMID- 29954187
TI - Generating toxic landscapes: impact on well-being of cotton farmers in Telangana,
India.
AB - Existing literature demonstrates agro-chemicals result in physical toxicity and
damages human health, flora and fauna. However, little is known about how such
'toxicity' relates to mental well-being and social suffering. This paper aims to
demonstrate how local, national and international vectors are interlinked to
shape social distress among cotton farmers in India. Ethnographic interviews and
focus group discussions were conducted in a cotton-growing village of the
Warangal district, Telangana state, India. The results advance the concept of
counter therapeutic spaces and hypothesise that toxic landscapes emerge through a
dynamic interaction between dispersed agencies that interact and reconfigure
agricultural spaces into socially toxic places. The paper argues that the
disciplines of public health and agriculture suffer from a failure of imagination
to forge vital interdisciplinary links that could address farmer suffering.
Unpacking local ecologies of farmer suffering offer innovative ways for enhancing
mental health policy and interventions in India.
PMID- 29954188
TI - Emergence of a virulent genotype VIIi of Newcastle disease virus in Iran.
AB - Newcastle disease (ND) is a contagious viral disease affecting numerous avian
species, particularly domestic poultry, and causes devastating outbreaks. In
spite of its endemicity and importance in Iran, data on the genetic
characterization of ND virus (NDV) are scarce. An alarming issue that has just
been raised is the occurrence of ND outbreaks with unexpected high mortality and
severe clinical signs. The present study was conducted to characterize the
emerging NDV genetically. An NDV strain, isolated in 2017 from commercial
broilers showing severe nervous and enteric signs, was completely sequenced and
found to be 15,192 nucleotides in length. The phylogenetic analysis demonstrated
that the virus belonged to subgenotype VIIi, a subgenotype with potential
panzootic features which has recently emerged in the Middle East and Asia. The
supporting genetic pattern obtained from the complete genome, fusion and
haemagglutinin gene analysis showed close relationship of the isolate with
Pakistani VIIi NDVs. The analysis of the F protein showed a polybasic amino acid
motif and a phenylalanine at position 117 at the cleavage site, which is a
characteristic of virulent strains. The isolate showed significant differences
from the previously characterized NDV strains from commercial and rural chickens
in Iran. This may describe the importance of the illegal trade of pet birds from
neighbouring countries leading to the emergence of new genotypes. This study
introduces a newly emerging NDV VIIi subgenotype in Iran. This investigation
emphasizes the necessity of effective control strategies.
PMID- 29954189
TI - Psychiatric hegemony: a Marxist theory of mental illness, by Bruce M. Z. Cohen.
PMID- 29954190
TI - Effect of a rehabilitation program on performance-related musculoskeletal
disorders in student and professional orchestral musicians: a randomized
controlled trial.
AB - OBJECTIVE:: To explore the feasibility of a rehabilitation program and its effect
on the performance-related musculoskeletal symptoms and functional limitations of
orchestral musicians. DESIGN:: Single-blind pilot randomized controlled trial
with exercise group and control group. SETTING:: Workplace of professional
symphony orchestra and tertiary-level conservatory orchestral musicians.
PARTICIPANTS:: Professional and student orchestral musicians with or without
performance-related musculoskeletal disorders. INTERVENTIONS:: A rehabilitation
program including an educational presentation, an 11-week home exercise program
and three supervised exercise sessions, versus no intervention. MEASURES::
Feasibility measures included adherence and drop-out rate. The Musculoskeletal
Pain Intensity and Interference Questionnaire for professional orchestra
Musicians (MPIIQM) measured symptom intensity and functional limitations, while
the Nordic Musculoskeletal Questionnaire (NMQ) measured symptom prevalence and
frequency. RESULTS:: A total of 30 participants were recruited ( n = 15 per
group). Exercise group adherence was 97.7% for the supervised sessions and 89%
for the home exercise program. There were no drop-outs. Significant group-time
interactions were obtained for both the pain intensity (partial eta2 = 0.166; P =
0.025) and pain interference (partial eta2 = 0.186; P = 0.017) sections of the
MPIIQM. Mean (standard deviation) pain intensity score changes from baseline to
11 weeks were control group: 0.40 (5.04); P = 0.763; partial eta2 = 0.007; and
exercise group: -4.07 (5.31); P = 0.010; partial eta2 = 0.386. For pain
interference, mean score changes were control group: 0.20 (9.10); P = 0.933;
partial eta2 = 0.001; and exercise group: -9.00 (10.73); P = 0.006; partial eta2
= 0.430. NMQ analyses revealed no significant interaction ( P > 0.05).
CONCLUSION:: Results suggest that the studied program is feasible and effective
in decreasing the intensity and functional impact of musicians' symptoms.
However, no significant medium-term effect on the prevalence and frequency of
symptoms was shown.
PMID- 29954191
TI - HIV-2 Infection in a Migrant from Gambia: The History of the Disease Combined
with Phylogenetic Analysis Revealed the Real Source of Infection.
AB - Human immunodeficiency virus type 2 (HIV-2) infection prevalence is increasing in
some European countries. The increasing migratory flow from countries where HIV-2
is endemic has facilitated the spread of the virus into Europe and other regions.
We describe a case of HIV-2 infection in a migrant individual in the Asylum
Seekers Centre (ASC) in Italy. The patient's virus was sequenced and found to be
a typical HIV-2 genotype A virus. Bayesian evolutionary analysis revealed that
the HIV-2 sequence from migrant dated back to 1986 in a subcluster, including
sequences from Guinea Bissau. This was coherent with the history of the migrant
who lived in Guinea Bissau from his birth until 1998 when he was 13 years old.
Monitoring for HIV-2 infection in migrants from western Africa is necessary using
adequate molecular tools to improve the diagnosis and understand the real origin
of infection.
PMID- 29954192
TI - Drinking water and chronic kidney disease of unknown aetiology in Anuradhapura,
Sri Lanka.
AB - This paper examines how people in Anuradhapura District in Sri Lanka affected by
endemic chronic kidney disease of unknown aetiology (CKDu) explain the factors
causing the illness and their cultural meanings. The research found that the
issue of contaminated water raised by the local community and the cultural
meaning of water have influenced the government policy, health programmes,
research agendas and the work of the media. Media reports on sociocultural,
biomedical and epidemiological research into the aetiology of kidney disease have
strengthened the perspective of the villagers who believe that polluted water has
a direct relationship to kidney disease. This new understanding among villagers
in Anuradhapura District has led to changes in their behaviours relating to the
use and consumption of water, an important factor that has reinforced existing
social hierarchies.
PMID- 29954193
TI - Characterization of unilateral conjunctival inoculation with Mycoplasma
gallisepticum in house finches.
AB - House finches in much of the continental United States experience annual
epidemics of mycoplasmal conjunctivitis, caused by the bacterial pathogen
Mycoplasma gallisepticum (MG). Although evidence suggests that natural infections
typically begin unilaterally, experimental inoculations of songbirds with MG to
date have all been administered bilaterally. Furthermore, studies of free-living
finches find more severe clinical signs of mycoplasmal conjunctivitis in left
versus right eyes, but the mechanisms underlying this side bias remain unknown.
Here, we characterized unilateral inoculation of house finches with MG, and
tested whether differential susceptibility of left versus right conjunctiva
explains the side bias in disease severity of free-living finches. We directly
inoculated house finches in either the left or right conjunctiva and
characterized resulting disease severity and pathogen load throughout the course
of infection. As expected, unilateral inoculation resulted in significantly more
severe conjunctivitis, as well as higher conjunctival bacterial loads, on
whichever side (left or right) birds were directly inoculated. However, in 55% of
cases, unilateral inoculations resulted in bilateral disease, and in 85% cases
there was evidence of bilateral infection. The overall severity of disease did
not differ for birds inoculated in the left versus right conjunctiva, suggesting
that physiological differences between the conjunctivae cannot explain the side
bias in disease severity of free-living birds. Instead, laterality in exposure,
perhaps due to feeding handedness, likely explains the detected field patterns.
RESEARCH HIGHLIGHTS House finches show more severe disease in the directly
inoculated conjunctiva. Unilateral inoculations lead to high rates of bilateral
infection and disease. Overall disease severity does not differ for the left- or
right-inoculated conjunctiva. Laterality in exposure likely explains the left
side bias in natural infections.
PMID- 29954194
TI - Two-centre radiological survivorship of acetabular distraction technique for
treatment of chronic pelvic discontinuity.
AB - Aims The aim of this study was to examine the results of the acetabular
distraction technique in achieving implantation of a stable construct, obtaining
biological fixation, and producing healing of chronic pelvic discontinuity at
revision total hip arthroplasty. Patients and Methods We identified 32 patients
treated between 2006 and 2013 who underwent acetabular revision for a chronic
pelvic discontinuity using acetabular distraction, and who were radiographically
evaluated at a mean of 62 months (25 to 160). Of these patients, 28 (87.5%) were
female. The mean age at the time of revision was 67 years (44 to 86). The
patients represented a continuous series drawn from two institutions that adhered
to an identical operative technique. Results Of the 32 patients, one patient
required a revision for aseptic loosening, two patients had evidence of
radiographic loosening but were not revised, and three patients had migration of
the acetabular component into a more stable configuration. Radiographically, 22
(69%) of the cohort demonstrated healing of the discontinuity. The Kaplan-Meier
construct survivorship was 83.3% when using revision for aseptic acetabular
loosening as an endpoint. At the time when one patient failed due to aseptic
loosening (at 7.4 years), there were a total of seven patients with a follow-up
of seven years or longer who were at risk of failure. Conclusion The acetabular
distraction technique demonstrates encouraging radiographic outcomes, with
healing of the discontinuity in over two-thirds of our series. This surgical
technique permits biological fixation and intraoperative customization of the
construct to be implanted based on the pattern of the bone loss identified
following component removal. Cite this article: Bone Joint J 2018;100-B:909-14.
PMID- 29954195
TI - Non-steroidal anti-inflammatory drugs for heterotopic ossification prophylaxis
after total hip arthroplasty.
AB - Aims: The aim of this study was to assess the efficacy of non-selective and
selective non-steroidal anti-inflammatory drugs (NSAIDs) in preventing
heterotopic ossification (HO) after total hip arthroplasty (THA). Methods: A
thorough and systematic literature search was conducted and 29 studies were found
that met inclusion criteria. Data were extracted and statistical analysis was
carried out generating forest plots. Results: Non-selective NSAIDs showed a
significant decrease in the odds for forming HO after THA (odds ratio (OR) -1.35,
confidence interval (CI) -1.83 to -0.86) when compared with placebo. Selective
NSAIDs also showed a significant decrease in the odds for forming HO after THA
when compared with placebo (OR -1.58, CI -2.41 to -0.75). When comparing non
selective NSAIDs with selective NSAIDs, there was no significant change in the
odds for forming HO after THA (OR 0.22, CI -0.36 to 0.79). Conclusion: Our meta
analyses of all available data suggest that both non-selective and selective
NSAIDs are effective HO prophylaxis and can be used routinely after THA for pain
control as well as prevention of HO. Indomethacin may serve as the benchmark
among non-selective NSAIDs and celecoxib among selective NSAIDs. There was no
difference in the incidence of HO between non-selective and selective NSAIDs,
allowing physicians to choose either based on the clinical scenario and patient
specific factors. Cite this article: Bone Joint J 2018;100-B:915-22.
PMID- 29954196
TI - Risk factors for increased sagittal pelvic motion causing unfavourable
orientation of the acetabular component in patients undergoing total hip
arthroplasty.
AB - Aims: It is important to consider sagittal pelvic rotation when introducing the
acetabular component at total hip arthroplasty (THA). The purpose of this study
was to identify patients who are at risk of unfavourable pelvic mobility, which
could result in poor outcomes after THA. Patients and Methods: A consecutive
series of 4042 patients undergoing THA had lateral functional radiographs and a
low-dose CT scan to measure supine pelvic tilt, pelvic incidence, standing pelvic
tilt, flexed-seated pelvic tilt, standing lumbar lordotic angle, flexed-seated
lumbar lordotic angle, and lumbar flexion. Changes in pelvic tilt from supine-to
standing positions and supine-to-flexed-seated positions were determined. A
change in pelvic tilt of 13 degrees between positions was deemed unfavourable as
it alters functional anteversion by 10 degrees and effectively places the
acetabular component outside the safe zone of orientation. Results: For both men
and women, the degree of lumbar flexion was a significant predictor of risk in
hip flexion (p < 0.0001) with increased odds of unfavourable pelvic mobility in
those with lumbar flexion of < 20 degrees (men, odds ratio (OR) 6.74, 95%
confidence interval (CI) 3.83 to 11.89; women, OR 2.97, 95% CI 1.87 to 4.71). In
women, age and standing pelvic tilt were significant predictors of risk in hip
extension (p = 0.0082 and p < 0.0001, respectively). The risk of unfavourable
pelvic mobility was higher in those aged > 75 years (OR 2.28, 95% CI 1.56 to
3.32) and those with standing pelvic tilt of < -10 degrees for extension risk
(OR 7.10, 95% CI 4.10 to 10.29). In men, only standing pelvic tilt was
significant (p < 0.0001) for hip extension with an increased risk of unfavourable
pelvic mobility (OR 8.68, 95% CI 5.19 to 14.51). Conclusion: Patients found to
have unfavourable pelvic mobility had limited lumbar flexion and more posterior
standing pelvic tilt in both men and women, as well as increasing age in women.
We recommend that patients undergo preoperative functional radiographic screening
to determine specific parameters that can affect the functional orientation of
the acetabular component. Cite this article: Bone Joint J 2018;100-B:845-52.
PMID- 29954197
TI - Results of trabecular metal augments in Paprosky IIIA and IIIB defects.
AB - Aims: The advent of trabecular metal (TM) augments has revolutionized the
management of severe bone defects during acetabular reconstruction. The purpose
of this study was to evaluate patients undergoing revision total hip arthroplasty
(THA) with the use of TM augments for reconstruction of Paprosky IIIA and IIIB
defects. Patients and Methods: A retrospective study was conducted at four
centres between August 2008 and January 2015. Patients treated with TM augments
and TM shell for a Paprosky grade IIIA or IIIB defect, in the absence of pelvic
discontinuity, and who underwent revision hip arthroplasty with the use of TM
augments were included in the study. A total of 41 patients with minimum follow
up of two years were included and evaluated using intention-to-treat analysis.
Results: There were 36 (87.8%) patients with a Paprosky IIIA defect and five
(12.2%) patients with a Paprosky IIIB defect. The mean age was 56.7 years (28 to
94). There were 21 (51.2%) women and 20 (48.8%) men. The mean follow-up was 39.4
months (12 to 96). One (2%) patient died after eight years. No failures were
noted in the series. The mean survivorship was 100% at the time of latest follow
up. Conclusion: The results of this multicentre study showed encouraging short-
and mid-term results for the use of TM augments in the management of Paprosky
grade IIIA and IIIB defects. Cite this article: Bone Joint J 2018;100-B:903-8.
PMID- 29954198
TI - Trunnion corrosion in metal-on-polyethylene hip arthroplasty.
AB - Aims: To report our experience with trunnion corrosion following metal-on
polyethylene total hip arthroplasty, in particular to report the spectrum of
presentation and determine the mean time to presentation. Patients and Methods:
We report the presenting symptoms and signs, intraoperative findings, and early
results and complications of operative treatment in nine patients with a mean age
of 74 years (60 to 86). The onset of symptoms was at a mean of seven years (3 to
18) after index surgery. Results: Patients presented with a variety of symptoms
including pain, limp and rash. The preoperative mean serum cobalt level was 7.1
ppb (2.2 to 12.8) and mean serum chromium level was 2.2 ppb (0.5 to 5.2). Metal
artifact reduction sequence (MARS) MRI showed fluid collection and possible
pseudotumour formation in five hips, fluid collection in two hips, and
synovitis/debris in one hip, with no MRI in one patient. Acetabular revision was
performed in three patients, six patients underwent liner and head exchange only.
The postoperative metal levels decreased in all patients: mean cobalt 0.5 ppb (0
to 1.8) and mean chromium 0.9 ppb (0 to 2.6) at a mean of five months (3 to 8)
postoperatively. Seven patients had good pain relief and no complications at one
year. There were two major complications requiring reoperation: acute infection
at six weeks, for which the patient required two-stage reimplantation; and
recurrent dislocation, for which the patient was revised to a dual mobility
component. Conclusion: Trunnion corrosion in metal-on-polyethylene THA has a
range of presenting symptoms, and may present later than previously described. A
high index of suspicion is warranted, and serum cobalt and chromium levels are
recommended for diagnosis. Patients should be counselled about possible
postoperative complications. Cite this article: Bone Joint J 2018;100-B:898-902.
PMID- 29954199
TI - A randomized controlled trial of fixed- versus mobile-bearing total knee
arthroplasty.
AB - Aims: It has been suggested that mobile-bearing total knee arthroplasty (TKA)
might lead to better outcomes by accommodating some femorotibial rotational
mismatch, thereby reducing contact stresses and polyethylene wear. The aim of
this study was to determine whether there is a difference between fixed- and
mobile-bearing versions of a contemporary TKA with respect to durability, range
of movement (ROM) and function, ten years postoperatively. Patients and Methods:
A total of 240 patients who were enrolled in this randomized controlled trial
(RCT) underwent a primary cemented TKA with one of three tibial components (all
polyethylene fixed-bearing, modular metal-backed fixed-bearing and mobile
bearing). Patients were reviewed at a median follow-up of ten years (IQR 9.2 to
10.4). Results: There was no difference in durability, as measured by
survivorship free of revision for any reason, nor in mean maximal ROM at ten
years (p = 0.8). There was also no difference in function, as measured by Knee
Society (KS) function scores (p = 0.63) or the prevalence of patellar tilt (p =
0.12). Conclusion: In this clinical RCT, the mobile-bearing design of TKA was
found to be reliable and durable, but did not provide better maximum knee
flexion, function or durability ten years postoperatively compared with a
posterior-stabilized, fixed-bearing design incorporating either an all
polyethylene or a modular-metal-backed tibial component. Cite this article: Bone
Joint J 2018;100-B:925-9.
PMID- 29954200
TI - Long-term results of scapulothoracic arthrodesis with multiple cable method for
facioscapulohumeral dystrophy.
AB - Aims: The present study aimed to investigate the long-term functional results of
scapulothoracic fusion using multifilament cables in patients with
facioscapulohumeral dystrophy (FSHD) to identify if the early improvement from
this intervention is maintained. Patients and Methods: We retrospectively
investigated the long-term outcomes of 13 patients with FSHD (18 shoulders) in
whom scapulothoracic fusion using multifilament cables was performed between 2004
and 2007. These patients have previously been reported at a mean of 35.5 months
(24 to 87). There were eight men and five women with a mean age of 26 years.
Their mean length of follow-up of our current study was 128 months (94 to 185).
To evaluate long-term functional results, the range of shoulder flexion and
abduction, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) scores
were analyzed with a comparison of preoperatively, interim and at the final
outcomes. The fusion was examined radiographically in all. Results: The
complication rate was 33% (six of 18 scapulothoracic fusions) in 13 patients,
which comprised failure of fusion in four shoulders (four patients) all occurring
within the first year postoperatively. In two shoulders (one patient) wound
problems arose due to attribution from the cables which required shortening but
the fusion developed satisfactorily. At the final examination, the mean QuickDASH
score and range of movement significantly improved in all but one patient (p <
0.001, p < 0.001 and p < 0.001). In the comparison of 13 patients' mid- and long
term results, the mean QuickDASH score decreased from 9.8 (sd 6.7; 3 to 26) in
the third year to 9.1 (sd 5.6; 3 to 22) in the tenth year (p = 0.7); the mean
range of shoulder flexion and abduction decreased from 129 degrees (sd 22
degrees ; 90 degrees to 160 degrees ) and 124 degrees (sd 12; 100 degrees to
150 degrees ) at the mid-term to 103 degrees (sd 12 degrees ; 80 degrees to 120
degrees ) and 101 degrees (sd 8 degrees ; 80 degrees to 120 degrees ) at the
long-term, respectively (p = 0.78 and p = 0.65). Conclusion: Scapulothoracic
fusion using a multiple cabling method can confer a considerable improvement in
clinical and functional outcomes for most patients with FSHD after a long follow
up period. The technique requires careful execution to avoid complications. Cite
this article: Bone Joint J 2018;100-B:953-6.
PMID- 29954201
TI - Infographic: Trauma Triage Clinic reduces unnecessary fracture clinic attendances
and costs with comparable clinical outcomes.
PMID- 29954202
TI - Highly crosslinked polyethylene wear rates and acetabular component orientation.
AB - Aims: The aim of this study was to determine whether there is a difference in the
rate of wear between acetabular components positioned within and outside the
'safe zones' of anteversion and inclination angle. Patients and Methods: We
reviewed 100 hips in 94 patients who had undergone primary total hip arthroplasty
(THA) at least ten years previously. Patients all had the same type of acetabular
component with a bearing couple which consisted of a 28 mm cobalt-chromium head
on a highly crosslinked polyethylene (HXLPE) liner. A supine radiostereometric
analysis (RSA) examination was carried out which acquired anteroposterior (AP)
and lateral paired images. Acetabular component anteversion and inclination
angles were measured as well as total femoral head penetration, which was divided
by the length of implantation to determine the rate of polyethylene wear.
Results: The mean anteversion angle was 19.4 degrees (-15.2 degrees to 48
degrees , sd 11.4 degrees ), the mean inclination angle 43.4 degrees (27.3
degrees to 60.5 degrees , sd 6.6 degrees ), and the mean wear rate 0.055 mm/year
(sd 0.060). Exactly half of the hips were positioned inside the 'safe zone'.
There was no difference (median difference, 0.012 mm/year; p = 0.091) in the rate
of wear between acetabular components located within or outside the 'safe zone'.
When compared to acetabular components located inside the 'safe zone', the wear
rate was no different for acetabular components that only achieved the target
anteversion angle (median difference, 0.012 mm/year; p = 0.138), target
inclination angle (median difference, 0.013 mm/year; p = 0.354), or neither
target (median difference, 0.012 mm/year; p = 0.322). Conclusion: Placing the
acetabular component within or outside the 'safe zone' did not alter the wear
rate of HXLPE at long-term follow-up to a level that risked osteolysis. HXLPE
appears to be a forgiving bearing material in terms of articular surface wear,
but care must still be taken to position the acetabular component correctly so
that the implant is stable. Cite this article: Bone Joint J 2018;100-B:891-7.
PMID- 29954203
TI - Evaluation of strategies for the treatment of type B and C pelvic fractures.
AB - Aims: The best method of treating unstable pelvic fractures that involve the
obturator ring is still a matter for debate. This study compared three methods of
treatment: nonoperative, isolated posterior fixation and combined anteroposterior
stabilization. Patients and Methods: The study used data from the German Pelvic
Trauma Registry and compared patients undergoing conservative management (n =
2394), surgical treatment (n = 1345) and transpubic surgery, including posterior
stabilization (n = 730) with isolated posterior osteosynthesis (n = 405) in non
complex Type B and C fractures that only involved the obturator ring anteriorly.
Calculated odds ratios were adjusted for potential confounders. Outcome criteria
were intraoperative and general short-term complications, the incidence of nerve
injuries, and mortality. Results: Operative stabilization reduced mortality by
36% (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.42 to 0.98) but the
incidence of complications was twice as high (OR 2.04, 95% CI 1.57 to 2.64).
Mortality and the incidence of neurological deficits at discharge were no
different after isolated posterior or combined anteroposterior fixation. However,
the odds of both surgical (98%, OR 1.98, 95%CI 1.22 to 3.22) and general
complications (43%, OR 1.43, 95% CI 1.02 to 2.00) were higher in the group with
the more extensive surgery. Conclusion: Operative stabilization is recommended
for non-complex unstable pelvic fractures. The need for anterior fixation of
obturator ring fractures should, however, be considered critically. Cite this
article: Bone Joint J 2018;100-B:973-83.
PMID- 29954204
TI - Prevalence of isolated gastrocnemius tightness in patients with foot and ankle
pathology.
AB - Aims: Gastrocnemius tightness predisposes to musculoskeletal pathology and may
require surgical treatment. However, it is not clear what proportion of patients
with foot and ankle pathology have clinically significant gastrocnemius
tightness. The aim of this study was to compare the prevalence and degree of
gastrocnemius tightness in a control group of patients with a group of patients
with foot and ankle pathology. Patients and Methods: This prospective, case
matched, observational study compared gastrocnemius tightness, as assessed by the
lunge test, in a control group and a group with foot and ankle pathology.
Gastrocnemius tightness was calculated as the difference in dorsiflexion of the
ankle with the knee extended and flexed. Results: A total of 291 controls were
paired with 97 patients with foot and ankle pathology (FAP). The mean
gastrocnemius tightness was 6.0 degrees (sd 3.5) in controls and 8.0 degrees
(sd 5.7) in the FAP group (p < 0.001). Subgroup analysis showed a mean
gastrocnemius tightness of 10.3 degrees (sd 6.0) in patients with forefoot
pathology versus 6.9 degrees (sd 5.3) in patients with other pathology (p =
0.008). A total of 12 patients (37.5%) with forefoot pathology had gastrocnemius
tightness of > two standard deviations of the control group (> 13 degrees ).
Conclusion: Gastrocnemius tightness of > 13 degrees may be considered abnormal.
Most patients with foot and ankle pathology do not have abnormal degrees of
gastrocnemius tightness compared with controls, but it is present in over a third
of patients with forefoot pathology. Cite this article: Bone Joint J 2018;100
B:945-52.
PMID- 29954205
TI - Are adverse outcome rates higher in multiple sclerosis patients after total hip
arthroplasty?
AB - Aims: This study compared multiple sclerosis (MS) patients who underwent primary
total hip arthroplasty (THA) with a matched cohort. Specifically, we evaluated:
1) implant survivorship; 2) functional outcomes (modified Harris Hip Scores
(mHHS), Hip Disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS
JR), and modified Multiple Sclerosis Impact Scale (mMSIS) scores (with the MS
cohort also evaluated based on the disease phenotype)); 3) physical therapy
duration and return to function; 4) radiographic outcomes; and 5) complications.
Patients and Methods: We reviewed our institution's database to identify MS
patients who underwent THA between January 2008 and June 2016. A total of 34 MS
patients (41 hips) were matched in a 1:2 ratio to a cohort of THA patients who
did not have MS, based on age, body mass index (BMI), and Charlson/Deyo score.
Patient records were reviewed for complications, and their functional outcomes
and radiographs were reviewed at their most recent follow-up. Results: Compared
with the matched cohort, MS patients had lower all-cause implant survivorship at
eight years (91.5% (95% confidence interval (CI) 82.7 to 100) vs 98.7% (95% CI
96.2 to 100)) (p = 0.033), lower mHHS scores (66 vs 80, p < 0.001), and HOOS JR
scores (79 vs 88, p = 0.009). Multiple sclerosis patients also required more
physiotherapy (five weeks vs three weeks, p = 0.002) and took longer to return to
baseline (seven weeks vs five weeks, p = 0.010) than the matched cohort.
Furthermore, MS patients had more complications than the non-MS patients (six vs
zero, p < 0.001). The worse outcomes of the MS group can potentially be explained
by predisposition of these patients to mechanical complications and progression
of their disease during the period of this study, as demonstrated by worsening of
the mMSIS scores (2.9 vs 3.4; p = 0.008). Conclusion: MS patients had lower
implant survivorship, lower functional outcome scores, and increased complication
rates; in addition, MS patients took longer to return to their baseline
functional level after THA. Cite this article: Bone Joint J 2018;100-B:875-81.
PMID- 29954206
TI - International Hip Society: a new partnership.
PMID- 29954207
TI - Does acetabular coverage influence the clinical outcome of arthroscopically
treated cam-type femoroacetabular impingement (FAI)?
AB - Aims: What represents clinically significant acetabular undercoverage in patients
with symptomatic cam-type femoroacetabular impingement (FAI) remains
controversial. The aim of this study was to examine the influence of the degree
of acetabular coverage on the functional outcome of patients treated
arthroscopically for cam-type FAI. Patients and Methods: Between October 2005 and
June 2016, 88 patients (97 hips) underwent arthroscopic cam resection and
concomitant labral debridement and/or refixation. There were 57 male and 31
female patients with a mean age of 31.0 years (17.0 to 48.5) and a mean body mass
index (BMI) of 25.4 kg/m2 (18.9 to 34.9). We used the Hip2Norm, an object
oriented-platform program, to perform 3D analysis of hip joint morphology using
2D anteroposterior pelvic radiographs. The lateral centre-edge angle, anterior
coverage, posterior coverage, total femoral coverage, and alpha angle were
measured for each hip. The presence or absence of crossover sign, posterior wall
sign, and the value of acetabular retroversion index were identified
automatically by Hip2Norm. Patient-reported outcome scores were collected
preoperatively and at final follow-up with the Hip Disability and Osteoarthritis
Outcome Score (HOOS). Results: At a mean follow-up of 2.7 years (1 to 8, sd 1.6),
all functional outcome scores significantly improved overall. Radiographically,
only preoperative anterior coverage had a negative correlation with the
improvement of the HOOS symptom subscale (r = -0.28, p = 0.005). No significant
difference in relative change in HOOS subscale scores was found according to the
presence or absence of radiographic signs of retroversion. Discussion: Our study
demonstrated the anterior coverage as an important modifier influencing the
functional outcome of arthroscopically treated cam-type FAI. Cite this article:
Bone Joint J 2018;100-B:831-8.
PMID- 29954208
TI - Discharged but not dissatisfied: outcomes and satisfaction of patients discharged
from the Edinburgh Trauma Triage Clinic.
AB - Aims: The Edinburgh Trauma Triage Clinic (TTC) streamlines outpatient care
through consultant-led 'virtual' triage of referrals and the direct discharge of
minor fractures from the Emergency Department. We compared the patient outcomes
for simple fractures of the radial head, little finger metacarpal, and fifth
metatarsal before and after the implementation of the TTC. Patients and Methods:
A total of 628 patients who had sustained these injuries over a one-year period
were identified. There were 337 patients in the pre-TTC group and 289 in the post
TTC group. The Disabilities of the Arm, Shoulder and Hand Score (QuickDASH) or
Foot and Ankle Disability Index (FADI), EuroQol-5D (EQ-5D), visual analogue scale
(VAS) pain score, satisfaction rates, and return to work/sport were assessed six
months post-injury. The development of late complications was excluded by an
electronic record evaluation at three years post-injury. A cost analysis was
performed. Results: Outcomes were as good or better post-TTC, compared with pre
TTC scores. At three years, the pre-TTC group required a total of 496 fracture
clinic appointments compared with 61 in the post-TTC group. Mean cost per patient
was nearly fourfold less after the commencement of the TTC. Conclusion:
Management of minor fractures through the Edinburgh TTC results in clinical
outcomes that are comparable with the previous system of routine face-to-face
consultation. Outpatient workload for these injures was reduced by 88%. Cite this
article: Bone Joint J 2018;100-B:959-65.
PMID- 29954209
TI - Which factors influence proximal femoral asymmetry?
AB - Aims: In patients where the proximal femur shows gross deformity due to
degenerative changes or fracture, the contralateral femur is often used to
perform preoperative templating for hip arthroplasty. However, femurs may not be
symmetrical: the aim of this study was to determine the degree of variation
between hips in healthy individuals and to determine whether it is affected by
demographic parameters. Materials and Methods: CT-scan based modelling was used
to examine the pelvis and bilateral femurs of 345 patients (211 males, 134 women;
mean age 62 years (standard deviation (sd) 17), mean body mass index 27 kg/m2 (sd
5)) representing a range of ethnicities. The femoral neck-shaft angle (NSA),
femoral offset (FO), femoral neck version (FNV), femoral length (FL), femoral
canal flare index (fCFI), and femoral head radius (FHr) were then determined for
each patient. All measurements were constructed using algorithm-calculated
landmarks, resulting in reproducible and consistent constructs for each specimen.
We then analyzed femoral symmetry based on absolute differences (AD) and
percentage asymmetry (%AS) following a previously validated method. Results: We
found an asymmetry > 2% for NSA (mean AD 2.9 degrees , mean %AS 2.3; p = 0.03),
FO (AD 3.8 mm, %AS 9.1 ; p = 0.01), FNV (AD 5.1 degrees , %AS 46.7 ; p = 0.001)
and fCFI (AD 0.2 mm, %AS 5.4 ; p = 0.7). Significant relationships were found for
AD regarding NSA and ethnicity (p = 0.037), FL and height (R2 = 0.22), and fCFI
and gender (R2 = 0.34). Conclusion: Our data confirm the presence of asymmetry of
proximal femurs, which is mostly independent of demographic parameters. In cases
where contralateral templating is used, such asymmetry may lead to inaccurate
anatomical restoration of the hip if the templated sizes are routinely implanted.
However, the clinical impact cannot be determined from our investigation. Cite
this article: Bone Joint J 2018;100-B:839-44.
PMID- 29954210
TI - CT pulmonary angiography in lower limb arthroplasty.
AB - Aims: The aims of this study were to determine the indications and frequency of
ordering a CT pulmonary angiography (CTPA) following primary arthroplasty of the
hip and knee, and to determine the number of positive scans in these patients,
the location of emboli and the outcome for patients undergoing CTPA. Patients and
Methods: We analyzed the use of CTPA, as an inpatient and up to 90 days as an
outpatient, in a cohort of patients and reviewed the medical records and imaging
for each patient undergoing CTPA. Results: Out of 11 249 patients, scans were
requested in 229 (2.04%) and 86 (38%) were positive. No patient undergoing CTPA
died within 90 days. The rate of mortality from pulmonary embolism (PE) overall
was 0.08%. CTPA was performed twice as often following total knee arthroplasty
(TKA) compared with total hip arthroplasty (THA), and when performed was twice as
likely to be positive. Hypoxia was the main indication for a scan, being the
indication in 149 scans (65%); and in 23% (11 of 47), the PE was peripheral and
unilateral. Three patients suffered complications resulting from therapeutic
anticoagulation for possible PE, two of whom had a negative CTPA. Conclusion:
CTPA is more likely to be performed following TKA compared with THA. Hypoxia was
the main presenting feature of PE. A quarter of PEs which were diagnosed were
unilateral and peripheral. Further study may indicate which patients who have a
PE after lower limb arthroplasty require treatment, and which can avoid the
complications associated with anticoagulation. Cite this article: Bone Joint J
2018;100-B:938-44.
PMID- 29954211
TI - Can the use of an inclinometer improve the positioning of the acetabular
component in total hip arthroplasty?
AB - Aims: Accurate placement of the acetabular component is essential in total hip
arthroplasty (THA). The purpose of this study was to determine if the ability to
achieve inclination of the acetabular component within the 'safe-zone' of 30
degrees to 50 degrees could be improved with the use of an inclinometer.
Patients and Methods: We reviewed 167 primary THAs performed by a single surgeon
over a period of 14 months. Procedures were performed at two institutions: an
inpatient hospital, where an inclinometer was used (inclinometer group); and an
ambulatory centre, where an inclinometer was not used as it could not be
adequately sterilized (control group). We excluded 47 patients with a body mass
index (BMI) of > 40 kg/m2, age of > 68 years, or a surgical indication other than
osteoarthritis whose treatment could not be undertaken in the ambulatory centre.
There were thus 120 patients in the study, 68 in the inclinometer group and 52 in
the control group. The inclination angles of the acetabular component were
measured from de-identified plain radiographs by two blinded investigators who
were not involved in the surgery. The effect of the use of the inclinometer on
the inclination angle was determined using multivariate regression analysis.
Results: The mean inclination angle for the THAs in the inclinometer group was
42.9 degrees (95% confidence interval (CI) 41.7 degrees to 44.0 degrees ; range
29.0 degrees to 63.8 degrees ) and 46.5 degrees (95% CI 45.2 degrees to 47.7
degrees ; range 32.8 degrees to 63.2 degrees ) in the control group (p < 0.001).
Regression analysis identified a 9.1% difference in inclination due to the use of
an inclinometer (p < 0.001), and THAs performed without the inclinometer were
three times more likely to result in inclination angles of > 50 degrees (odds
ratio (OR) 2.8, p = 0.036). The correlation coefficient for the interobserver
reliability of the measurement of the two investigators was 0.95 (95% CI 0.93 to
0.97). Conclusion: The use of a simple inclinometer resulted in a significant
reduction in the number of outliers compared with a freehand technique. Cite this
article: Bone Joint J 2018;100-B:862-6.
PMID- 29954212
TI - Ten-year survivorship of primary total hip arthroplasty in patients 30 years of
age or younger.
AB - Aims: For this retrospective cohort study, patients aged <= 30 years (very young)
who underwent total hip arthroplasty (THA) were compared with patients aged >= 60
years (elderly) to evaluate the rate of revision arthroplasty, implant survival,
the indications for revision, the complications, and the patient-reported
outcomes. Patients and Methods: We retrospectively reviewed all patients who
underwent primary THA between January 2000 and May 2015 from our institutional
database. A total of 145 very young and 1359 elderly patients were reviewed. The
mean follow-up was 5.3 years (1 to 18). Logistic generalized estimating equations
were used to compare characteristics and the revision rate. Survival was
evaluated using Kaplan-Meier curves and hazard rates were created using Cox
regression. Results: The overall revision rate was 11% (16/145) in the very young
and 3.83% (52/1359) in the elderly groups (odds ratio (OR) 2.58, 95% confidence
interval (CI) 1.43 to 4.63). After adjusting for the American Society of
Anesthesiologists (ASA) score, gender, and a history of previous surgery in a
time-to-event model, the risk of revision remained greater in the very young
(adjusted hazard ratio (HR) 2.48, 95% CI 1.34 to 4.58). Survival at ten years was
82% (95% CI, 71 to 89) in the very young and 96% (95% CI, 94 to 97) in the
elderly group (p < 0.001). The very young had a higher rate of revision for
complications related to metal-on-metal (MoM) bearing surfaces (p < 0.001). At
last follow-up, the very young group had higher levels of physical function (p =
0.002), lower levels of mental health (p = 0.001), and similar levels of pain (p
= 0.670) compared with their elderly counterparts. Conclusion: The overall
revision rate was greater in very young THA patients. This was largely explained
by the use of MoM bearings. Young patients with non-MoM bearings had high
survivorship with similar complication profiles to patients aged >= 60 years.
Cite this article: Bone Joint J 2018;100-B:867-74.
PMID- 29954213
TI - Infographic: Fixed- versus mobile-bearing total knee arthroplasty at ten years.
PMID- 29954214
TI - Inconclusive benefit of adjuvant 90Yttrium hydroxyapatite to radiosynovectomy for
diffuse-type tenosynovial giant-cell tumour of the knee.
AB - Aims: Intra-articular 90Yttrium (90Y) is an adjunct to surgical treatment by
synovectomy for patients with diffuse-type tenosynovial giant-cell tumour
(dtTGCT) of the knee, with variable success rates. Clinical information is,
however, sparse and its value remains unclear. We investigated the long-term
outcome of patients who underwent synovectomy with and without adjuvant treatment
with 90Yttrium. Patients and Methods: All patients with dtTGCT of the knee who
underwent synovectomy between 1991 and 2014 were included in the study. Group A
patients underwent synovectomy and an intra-articular injection of 90Yttrium
between six and eight weeks after surgery. Group B patients underwent surgery
alone. Results: There were 34 patients in group A and 22 in group B. Recurrence
of dtTGCT was identified by MRI, which was undertaken in patients with further
symptoms. At a mean follow-up of 7.3 years (2.5 to 25.4), there was residual
disease in 15 patients in group A and 11 in group B (p < 0.363). The mean
Musculoskeletal Tumor Society (MSTS) score at final follow-up was 85% and 83%,
respectively (p < 0.91). Conclusion: There were no significant differences in
outcome between patients treated surgically for dtTGCT of the knee with or
without an adjuvant intra-articular injection of 90Yttrium. We were unable to
provide conclusive evidence of any benefits derived from the adjuvant treatment.
Cite this article: Bone Joint J 2018;100-B:984-8.
PMID- 29954215
TI - The value of quantitative histology in the diagnosis of fracture-related
infection.
AB - Aims: This study aimed to investigate the role of quantitative histological
analysis in the diagnosis of fracture-related infection (FRI). Patients and
Methods: The clinical features, microbiology culture results, and histological
analysis in 156 surgically treated nonunions were used to stratify the likelihood
of associated infection. There were 64 confirmed infected nonunions (one or more
confirmatory criteria: pus, sinus, and bacterial growth in two or more samples),
66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected
nonunions (pathogen identified from a single specimen and no confirmatory
criteria). The histological inflammatory response was assessed by average
neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with
the established diagnosis. Results: Assuming a cut-off of over five neutrophils
per high-power field to diagnose septic nonunion, there was 80% sensitivity and
100% specificity (accuracy 90%). Using a cut-off of no neutrophils seen in any
high-power field to diagnose aseptic nonunion, there was a sensitivity of 85% and
a specificity of 98% (accuracy 92%). Conclusion: Histology can be used in a
bimodal fashion as a diagnostic test for FRI. The presence of more than five
NPs/HPF had a positive predictive value for infected nonunion of 100%, while the
complete absence of any NPs is almost always indicative of an aseptic nonunion
(positive predictive value of 98%). Cite this article: Bone Joint J 2018;100
B:966-72.
PMID- 29954216
TI - Ceramic prosthesis surfaces induce an inflammatory cell response and fibrotic
tissue changes.
AB - Aims: Early evidence has emerged suggesting that ceramic-on-ceramic articulations
induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal
bearings. Therefore, the aim of this study was to investigate the tissue reaction
and cellular response to ceramic total hip arthroplasty (THA) materials in vitro,
as well as the tissue reaction in capsular tissue after revision surgery of
ceramic-on-ceramic THAs. Patients and Methods: We investigated tissue collected
at revision surgery from nine ceramic-on-ceramic articulations. we compared our
findings with tissue obtained from five metal-on-metal THA revisions, four
ceramic-on-polyethylene THAs, and four primary osteoarthritis synovial membranes.
The latter were analyzed to assess the amount of tissue fibrosis that might have
been present at the time of implantation to enable evaluation, in relation to
implantation time, of any subsequent response in the tissues. Results: There was
a significant increase in tissue fibrosis with implantation time for all implant
types tested. Interestingly, the tissue fibrosis in ceramic-on-ceramic THAs was
significantly increased compared with metal-on-metal and ceramic-on-polyethylene.
Additionally, we found ceramic wear particles in the periprosthetic tissue of
ceramic implants. Fibroblasts responded with expression of cytokines when
cultured on alumina-toughened zirconia (ATZ) and zirconia-toughened alumina (ZTA)
ceramic surfaces. This response was more pronounced on ATZ ceramics compared with
ZTA ceramics. The same inflammatory response was observed with peripheral blood
mononuclear cells (PBMCs) cultured on ZTA and ATZ. Conclusion: Our findings
therefore, corroborate the previous findings that ceramic-on-ceramic
periprosthetic revision tissue is fibrous and offer an explanation for this
observation. We detected a long-term inflammatory response of PBMCs and an
inflammatory response of fibroblasts to ATZ and ZTA ceramic. These findings
partially explain the fibrotic tissue change in periprosthetic tissue of ceramic
on-ceramic bearings. Cite this article: Bone Joint J 2018;100-B:882-90.
PMID- 29954217
TI - Robotic-arm assisted total knee arthroplasty is associated with improved early
functional recovery and reduced time to hospital discharge compared with
conventional jig-based total knee arthroplasty.
AB - Aims: The objective of this study was to compare early postoperative functional
outcomes and time to hospital discharge between conventional jig-based total knee
arthroplasty (TKA) and robotic-arm assisted TKA. Patients and Methods: This
prospective cohort study included 40 consecutive patients undergoing conventional
jig-based TKA followed by 40 consecutive patients receiving robotic-arm assisted
TKA. All surgical procedures were performed by a single surgeon using the medial
parapatellar approach with identical implant designs and standardized
postoperative inpatient rehabilitation. Inpatient functional outcomes and time to
hospital discharge were collected in all study patients. Results: There were no
systematic differences in baseline characteristics between the conventional jig
based TKA and robotic-arm assisted TKA treatment groups with respect to age (p =
0.32), gender (p = 0.50), body mass index (p = 0.17), American Society of
Anesthesiologists score (p = 0.88), and preoperative haemoglobin level (p =
0.82). Robotic-arm assisted TKA was associated with reduced postoperative pain (p
< 0.001), decreased analgesia requirements (p < 0.001), decreased reduction in
postoperative haemoglobin levels (p < 0.001), shorter time to straight leg raise
(p < 0.001), decreased number of physiotherapy sessions (p < 0.001) and improved
maximum knee flexion at discharge (p < 0.001) compared with conventional jig
based TKA. Median time to hospital discharge in robotic-arm assisted TKA was 77
hours (interquartile range (IQR) 74 to 81) compared with 105 hours (IQR 98 to
126) in conventional jig-based TKA (p < 0.001). Conclusion: Robotic-arm assisted
TKA was associated with decreased pain, improved early functional recovery and
reduced time to hospital discharge compared with conventional jig-based TKA. Cite
this article: Bone Joint J 2018;100-B:930-7.
PMID- 29954218
TI - Skin crease 'bikini' incision for the direct anterior approach in total hip
arthroplasty.
AB - Aims: The classical longitudinal incision used for the direct anterior approach
(DAA) to the hip does not follow the tension lines of the skin and can lead to
impaired wound healing and poor cosmesis. The purpose of this retrospective study
was to determine the satisfaction with the scar, and functional and radiographic
outcomes comparing the classic longitudinal incision with a modified skin crease
'bikini' when the DAA is used for total hip arthroplasty (THA). Patients and
Methods: A total of 964 patients (51% female; 59% longitudinal, 41% 'bikini')
completed a follow-up questionnaire between two and four years postoperatively,
including the Oxford Hip Score (OHS), the University of North Carolina '4P' scar
scale (UNC4P) and two items for assessing the aesthetic appearance of the scar
and symptoms of numbness. The positioning of the components, rates of heterotopic
ossification (HO) and rates of revision were assessed. Results: The mean OHS was
similar in both groups (p = 0.41). The mean UNC4P total score was slightly better
(p = 0.01) and the proportion of patients who were very satisfied with the
cosmetic aspects of the scar was higher in the 'bikini' group (p < 0.001). The
proportion of patients reporting numbness in the scar was higher in the
longitudinal group (14.5% vs 7.5%, respectively, p < 0.001). The abduction angle
of the acetabular component, the position of the stem and rates of HO did not
differ between the groups. There were no differences in the revision rates of
both groups, being 2.3% in the longitudinal and 1.5% in the 'bikini' group (p =
0.911). Conclusion: We found that a short oblique 'bikini' skin crease incision
is safe when used for the DAA at THA, without compromising the positioning of the
components or increasing the rate of lateral femoral cutaneous nerve
dysaesthesia. Although it leads to a superior scar satisfaction, as it is less
extensile, it should be used after having gained experience with the classic
longitudinal incision. Cite this article: Bone Joint J 2018;100-B:853-61.
PMID- 29954219
TI - The Flaws and Future of Islet Volume Measurements.
AB - When working with isolated islet preparations, measuring the volume of tissue is
not a trivial matter. Islets come in a large range of sizes and are often
contaminated with exocrine tissue. Many factors complicate the procedure, and yet
knowledge of the islet volume is essential for predicting the success of an islet
transplant or comparing experimental groups in the laboratory. In 1990, Ricordi
presented the islet equivalency (IEQ), defined as one IEQ equaling a single
spherical islet of 150 MUm in diameter. The method for estimating IEQ was
developed by visualizing islets in a microscope, estimating their diameter in 50
MUm categories and calculating a total volume for the preparation. Shortly after
its introduction, the IEQ was adopted as the standard method for islet volume
measurements. It has helped to advance research in the field by providing a
useful tool improving the reproducibility of islet research and eventually the
success of clinical islet transplants. However, the accuracy of the IEQ method
has been questioned for years and many alternatives have been proposed, but none
have been able to replace the widespread use of the IEQ. This article reviews the
history of the IEQ, and discusses the benefits and failings of the measurement. A
thorough evaluation of alternatives for estimating islet volume is provided along
with the steps needed to uniformly move to an improved method of islet volume
estimation. The lessons learned from islet researchers may serve as a guide for
other fields of regenerative medicine as cell clusters become a more attractive
therapeutic option.
PMID- 29954220
TI - Mesenchymal Stem Cell-Derived Extracellular Vesicles Improve the Renal
Microvasculature in Metabolic Renovascular Disease in Swine.
AB - BACKGROUND: Extracellular vesicles (EVs) released from mesenchymal stem/stromal
cells (MSCs) mediate their paracrine effect, but their efficacy to protect the
microcirculation of the kidney is unknown. Using a novel swine model of
unilateral renovascular disease (RVD) complicated by metabolic syndrome (MetS),
we tested the hypothesis that EVs would attenuate renal microvascular loss.
METHODS: Four groups of pigs ( n = 7 each) were studied after 16 weeks of diet
induced MetS and RVD (MetS+RVD), MetS+RVD treated 4 weeks earlier with a single
intra-renal delivery of EVs harvested from autologous adipose tissue-derived
MSCs, and Lean and MetS Sham controls. Stenotic-kidney renal blood flow (RBF) and
glomerular filtration rate (GFR) were measured in-vivo (fast CT), whereas EV
characteristics, renal microvascular architecture (micro-CT), and injury pathways
were studied ex-vivo. RESULTS: mRNA sequencing and proteomic analysis revealed
that EVs are packed with several pro-angiogenic genes and proteins, such as
vascular endothelial growth factor. Labeled EVs were detected in the stenotic
kidney 4 weeks after injection internalized by tubular and endothelial cells. EVs
restored renal expression of angiogenic factors and improved cortical
microvascular and peritubular capillary density. Renal apoptosis, oxidative
stress, tubular injury, and fibrosis were also attenuated in EV-treated pigs. RBF
and GFR decreased in MetS+RVD compared with MetS, but normalized in MetS+RVD+EVs.
CONCLUSIONS: Intra-renal delivery of MSC-derived EVs bearing pro-angiogenic
properties restored the renal microcirculation and in turn hemodynamics and
function in chronic experimental MetS+RVD. Our study suggests a novel therapeutic
potential for MSC-derived EVs in restoring renal hemodynamics in experimental
MetS+RVD.
PMID- 29954221
TI - Development of a Simple In Vitro Assay to Assess Digestion of the Extracellular
Matrix of the Human Pancreas by Collagenase Enzyme Blends.
AB - Despite huge advances in the field of islet transplantation over the last two
decades, current islet isolation methods remain suboptimal, with transplantable
yields obtained in less than half of all pancreases processed worldwide.
Successful islet isolation is dependent on the ability of collagenase-based
enzyme blends to digest extracellular matrix components at the islet-exocrine
interface. The limited availability of donor pancreases hinders the use of full
scale islet isolations to characterize pancreas digestion by different enzyme
components or blends, or allow the influence of inter-pancreatic variability
between donors to be explored. We have developed a method that allows multiple
enzyme components to be tested on any one pancreas. Biopsies of 0.5 cm3 were
taken from seven standard (age >=45) and eight young (age <=35) pancreases.
Serial cryosections were treated with Serva collagenase, neutral protease (NP),
or the two enzymes together at clinically relevant concentrations. Following
digestion, insulin and either collagen IV or laminin-alpha5 were detected by
immunofluorescent labeling. Protein loss at the islet-exocrine interface was semi
quantified morphometrically, with reference to a control section. Differential
digestion of the two proteins based on the enzyme components used was seen, with
protein digestion significantly influenced by donor age. Treatment with
collagenase and NP alone was significantly more effective at digesting collagen
IV in the standard donor group, as was the NP mediated digestion of laminin
alpha5. Collagenase alone was not capable of significantly digesting laminin
alpha5 in either donor group. Combining the two enzymes ameliorated the age
related differences in the digestion of both proteins. No significant differences
in protein loss were detected by the method when analyzed by two independent
operators, demonstrating the reproducibility of the assay. The development of
this simple yet reproducible assay has implications for both enzyme batch testing
and identifying inter-donor digestion variability, while utilizing small amounts
of both enzyme and human tissue.
PMID- 29954222
TI - Biotransformation and bioactivation reactions - 2017 literature highlights *.
AB - This annual review is the third one to highlight recent advances in the study and
assessment of biotransformations and bioactivations ( Table 1 ). We followed the
same format as the previous years with selection and authoring each section (see
Baillie et al. 2016 ; Khojasteh et al. 2017 ). We acknowledge that many
universities no longer train students in mechanistic biotransformation studies
reflecting a decline in the investment for those efforts by public funded
granting institutions. We hope this work serves as a resource to appreciate the
knowledge gained each year to understand and hopefully anticipate toxicological
outcomes dependent on biotransformations and bioactivations. This effort itself
also continues to evolve. I am pleased that Drs. Rietjens and Miller have again
contributed to this annual review. We would like to welcome Kaushik Mitra as an
author for this year's issue, and we thank Deepak Dalvie for his contributions to
last year's edition. We have intentionally maintained a balance of authors such
that two come from an academic setting and two come from industry. As always,
please drop us a note if you find this review helpful. We would be pleased to
hear your opinions of our commentary, and we extend an invitation to anyone who
would like to contribute to a future edition of this review.
PMID- 29954223
TI - Designs of Empirical Evaluations of Nonexperimental Methods in Field Settings.
AB - Over the last three decades, a research design has emerged to evaluate the
performance of nonexperimental (NE) designs and design features in field
settings. It is called the within-study comparison (WSC) approach or the design
replication study. In the traditional WSC design, treatment effects from a
randomized experiment are compared to those produced by an NE approach that
shares the same target population. The nonexperiment may be a quasi-experimental
design, such as a regression-discontinuity or an interrupted time-series design,
or an observational study approach that includes matching methods, standard
regression adjustments, and difference-in-differences methods. The goals of the
WSC are to determine whether the nonexperiment can replicate results from a
randomized experiment (which provides the causal benchmark estimate), and the
contexts and conditions under which these methods work in practice. This article
presents a coherent theory of the design and implementation of WSCs for
evaluating NE methods. It introduces and identifies the multiple purposes of
WSCs, required design components, common threats to validity, design variants,
and causal estimands of interest in WSCs. It highlights two general approaches
for empirical evaluations of methods in field settings, WSC designs with
independent and dependent benchmark and NE arms. This article highlights
advantages and disadvantages for each approach, and conditions and contexts under
which each approach is optimal for addressing methodological questions.
PMID- 29954224
TI - Assessing Treatment Effects That Capture Disease Burden in Serious Chronic
Diseases.
AB - Serious and chronic health conditions such as cardiovascular diseases (CVDs) are
posing challenges to the health system. Recently clinical trials in these fields
have focused on composite endpoints that take into account both disease-related
mortality and major disease-related morbidity events. It is the time to the first
component of the composite endpoint experienced by a patient that is the
traditional study endpoint and treatment aims are to delay the time to the first
event and to reduce its frequency. As the name implies, the time-to-first
composite event analysis approach focuses only on the first composite event and
ignores subsequent events. For a chronic disease, this can lead to a substantial
loss of potentially important information. For instance, in chronic heart failure
(HF) studies, the traditional composite endpoint of HF-related hospitalizations
and CVD death will ignore CVD deaths that are preceded by HF-related
hospitalizations. This paper explores the limitations of the traditional time-to
first event approach and discusses the potential value of incorporating all
events. The authors argue that endpoints capturing recurrent event information
can lead to interpretable measures of treatment effect that better reflect
disease burden than traditional time-to-first event endpoints by using the
available information beyond the first event. This paper aims to raise awareness
of the value and potential pitfalls of alternative treatment effect measures to
facilitate meaningful cross-functional conversations among trialists and other
stakeholders such as regulators, payers, and treating physicians who all are
striving to the same goal-to deliver the most effective treatments to patients.
PMID- 29954225
TI - CT-Based Diagnosis of Low Vertebral Bone Mineral Density Is Associated with
Hypercalciuria and Hypocitraturia on Opportunistic Imaging.
AB - INTRODUCTION AND OBJECTIVES: Studies have demonstrated associations between
nephrolithiasis and systemic conditions, including low bone mineral density
(BMD), which may correlate with hypercalciuria in kidney stone formers (KSFs).
Traditionally, low BMD is diagnosed with dual-energy X-ray absorptiometry. As a
noncontrast CT (NCCT) scan is typically part of a stone evaluation, our objective
was to evaluate the association of NCCT-based vertebral BMD with 24-hour urine
parameters in KSF. MATERIALS AND METHODS: This is a retrospective analysis of 99
KSFs who had CT imaging and 24-hour urine studies. For each patient, BMD was
estimated at the L1 vertebral body and CT attenuation measured in HU. A threshold
of 160 HU was chosen to distinguish normal from low BMD. Univariate and
multivariate logistic regression analysis was performed to compare patients with
low and normal BMD. Multivariate linear regression was performed to assess for
variables associated with 24-hour urine parameters. RESULTS: Patients with low
BMD had higher 24-hour urine calcium (219 vs 147 mg/day, p < 0.0001) and larger
stone volume (259 vs 78.4 mm3, p = 0.009). Multivariate analysis demonstrated age
>60 years (odds ratio [OR] 9.3, p < 0.0001) and hypercalciuria (OR 4.34, p =
0.004) correlated with low BMD. Linear regression demonstrated that lower BMD was
associated with higher urinary calcium (beta-coefficient -0.268, p = 0.009) and
lower urinary citrate (beta-coefficient 0.332, p = 0.01). CONCLUSIONS: CT-based
diagnosis of low mineral bone density is associated with derangement in 24-hour
urine calcium and citrate in KSFs, as well as larger stone volumes.
PMID- 29954226
TI - Expression of vitamin D receptors in the superior cervical ganglia of rats.
AB - We investigated the role of vitamin D in the sympathetic nervous system including
the distribution of vitamin D receptors (VDR), 1alpha-hydroxylase and 24
hydroxylase (CYP24) in neuronal subpopulations and satellite glia in the superior
cervical ganglia (SCGs) of rats using immunohistochemistry. VDR immunoreactivity
was observed in the cytoplasm and nucleus of nearly all neurons in the SCG.
Intensity of VDR fluorescence was significantly greater in the cytoplasm of
neuropeptide Y (NPY) negative somata compared to NPY positive neurons.
Immunoreactivity for 1alpha-hydroxylase also was observed in the cytoplasm of all
neurons of the SCG, but the intensity of fluorescence was less in the nuclei. To
the contrary, the immunoreactivity for CYP24 was stronger in the nuclei, although
it was present at lower intensity also in the cytoplasm of neurons. VDR and
1alpha-hydroxylase immunofluorescence was observed in many non-neuron cells,
except satellite glial cells, which exhibited weak CYP24 immunofluorescence.
Expression of VDRs and key metabolizing enzymes indicated the importance of
vitamin D in the autonomic nervous system and the ability of sympathetic neurons
to activate and deactivate vitamin D for its autocrine and paracrine roles.
PMID- 29954227
TI - Factors influencing the properties and the stability of spray-dried Sennae
fructus extracts.
AB - OBJECTIVE: The objective of this study was to characterize the properties of
aqueous Sennae fructus extracts prepared by spray-drying at varying process
conditions. SIGNIFICANCE: From an industrial point of view it is essential to
develop a formulation which has a constant quality over the whole period of its
specified shelf-life. METHOD: Sennae fructus extracts were spray-dried with
different atomizing gas pressures, pump feed rates, and inlet temperatures. The
extracts were analyzed for their physical properties and stored at accelerated
conditions. Sennoside degradation was monitored by HPLC analysis. RESULTS: An
increase of the atomizing gas pressure had the most pronounced influence on the
decrease of moisture content and particle size. An increase of the inlet
temperature led to a decrease of moisture content and particle density, as well
as an increase of smooth particle amount. An increase in the pump feed rate,
increased the moisture content and resulted in stable hollow spheres. The
different conditions also led to smooth or wrinkled particle surfaces, and to
golfball, donut, and shard particle shapes. The chemical stability of the
sennosides differed from each other after storage. Stability-reducing factors
were the moisture content of the samples and their hygroscopicities, as well as
different particle morphologies. These factors were influenced by the inlet
temperature of the spray-drying process. High inlet temperatures led to a
positive influence on dryness and particle morphology and therefore on the
stability of the sennosides. CONCLUSIONS: Variation of the process conditions
affected the resulting particle properties and their storage stability of Sennae
fructus extract.
PMID- 29954228
TI - Effects of xylitol and stevioside on the physical and rheological properties of
gelatin from cod skin.
AB - Jelly and confectionery products are high in sugar and calories. Xylitol and
stevioside are natural low-calorie sweeteners and they can be used as an
alternative; however, their effects on fish gelatin are unknown. The gelatin was
extracted from cod skins and added to xylitol or stevioside (0, 2, 6, 10, 14, and
20% (w/v)) to form gel products. This paper investigated how xylitol and
stevioside affected the physical and rheological behaviors of fish gelatin, such
as color, gel strength, texture profile analysis, storage modulus (G'), loss
modulus (G"), and viscosity. Results showed that the change of color and
viscosity in gel products were similar when various concentrations of xylitol or
stevioside were added to the fish gelatin. But the effects of xylitol/stevioside
on texture profile analysis and G', G" were different, which might due to the
structure variation in xylitol and stevioside. The linear structure of xylitol
resulted in ionic interaction, hydrogen bonding, van der Waals forces, and
hydrophobic association between xylitol and fish gelatin. Therefore, xylitol is a
promising sweetener substitute, which was probably related to its greater
solubility and number of -OH groups.
PMID- 29954229
TI - Responsiveness and predictive validity of the computerized digit vigilance test
in patients with stroke.
AB - PURPOSE: To investigate the responsiveness and predictive validity of the
computerized digit vigilance test (C-DVT) in inpatients receiving rehabilitation
following stroke. METHODS: Forty-nine patients completed the C-DVT and the
Barthel Index (BI) after admission to and before discharge from the
rehabilitation ward. The standardized response mean (SRM) was used to examine the
responsiveness of the C-DVT. We used a paired t-test to determine the statistical
significance of the changes in scores on the C-DVT. We estimated the predictive
validity of the C-DVT with the Pearson correlation coefficient (r) to investigate
the association between the scores of the C-DVT at admission and the scores of
the BI at discharge. RESULTS: Our data showed a small SRM (-0.31) and a
significant difference (paired t-test, p = 0.034) between the C-DVT scores at
admission and discharge. These findings indicate that the C-DVT can appropriately
detect changes in sustained attention. In addition, we found a moderate
association (r = 0.48) between the scores of the C-DVT at admission and the
scores of the BI at discharge, suggesting the sufficient predictive validity of
the C-DVT. CONCLUSIONS: Our results showed that the C-DVT had adequate
responsiveness and sufficient predictive validity in inpatients receiving
rehabilitation following stroke. Implications for rehabilitation The computerized
digit vigilance test (C-DVT) had adequate responsiveness to be an outcome measure
for assessing the sustained attention in inpatients receiving rehabilitation
after stroke. The C-DVT had sufficient predictive validity to predict daily
function in inpatients receiving rehabilitation after stroke.
PMID- 29954230
TI - Is failure to raise concerns about misconduct a breach of integrity? Researchers'
reflections on reporting misconduct.
AB - This article describes and discusses the views of researchers on the significance
of raising concerns about scientific misconduct in their work environment and the
reasons or circumstances that might deter them from doing so. In this exploratory
qualitative research study, we conducted in-depth interviews with 33 researchers
working in life sciences and medicine. They represent three seniority levels and
five universities across Switzerland. A large majority of respondents in this
research study argued that failure to raise concerns about scientific misconduct
compromises research integrity. This is an encouraging result demonstrating that
researchers try to adhere to high ethical standards. However, further interaction
with respondents highlighted that this correct ethical assessment does not lead
researchers to take the consequent action of raising concerns. The factors that
discourage researchers from raising concerns need to be addressed at the level of
research groups, institutions, and by setting a positive precedent which helps
them to believe in the system's ability to investigate concerns raised in a
timely and professional manner. Training of researchers in research integrity
related issues will have limited utility unless it is coupled with the creation
of research culture where raising concerns is a standard practice of scientific
and research activities.
PMID- 29954231
TI - Unmoving and unmoved: experiences and consequences of impaired non-verbal
expressivity in Parkinson's patients and their spouses.
AB - PURPOSE: Hypomimia, or facial masking, is a decrease in voluntary control and
spontaneous movement of the muscles of the face, which may occur in Parkinson's
disease. Little is known about the psychosocial consequences or management of
this symptom. The aim of this study was to provide an initial overview of patient
& spousal experiences of living with an acquired nonverbal expressive impairment
in Parkinson's disease. METHOD: This qualitative study involved a community
sample of individuals with Parkinson's who experienced facial masking, and their
close romantic partners. Nine people who had Parkinson's and nine of their
spouses or partners participated in separate (individual) semi-structured
interviews. RESULTS: A descriptive thematic approach was used to analyze the
interview data. Key themes relevant to rehabilitation included the
misidentification of masking as negative affect, poor symptom recognition, and
unmet health resource needs. CONCLUSIONS: The results indicate masking can have
an adverse impact on close relationships and psychological well-being. This study
presents an initial basis for clinicians working with Parkinson's populations to
recognize of the needs of people who experience masking and better support such
individuals and their families to live satisfying social and emotional lives.
Implications for Rehabilitation People who have Parkinson's and their families
are often unaware facial masking is a symptom of Parkinson's disease. Masking may
be confused with negative affect and become a barrier to satisfying close
relationships. Masking related health resources and support are perceived to be
of poor availability and quality. This qualitative study suggests masking be
considered as an etiology of interpersonal and psychological difficulties in
Parkinson's disease, and encourages better recognition of this unique
population's health education needs.
PMID- 29954232
TI - The methodological application of goal attainment scaling in pediatric
rehabilitation research: a systematic review.
AB - PURPOSE: The objectives of this review article were to (1) describe the
populations and interventions to which Goal Attainment Scaling (GAS) has been
applied in pediatric rehabilitation, (2) summarize the scientific rigor of
published studies utilizing GAS as an outcome measure in pediatric
rehabilitation, and (3) illustrate the responsiveness of GAS following
intervention. MATERIALS AND METHODS: Four electronic databases were searched for
English language, human subject studies. Two reviewers independently extracted
data, graded evidence, and rated study quality. RESULTS: Fifty-two studies
utilizing GAS as an outcome measure within pediatric rehabilitation were
included. A majority of studies were characterized as low-level evidence in the
Sackett hierarchy (Sackett levels IV-V; 33 of 52). Quality appraisal scores for
all reviewed studies ranged from 1-13 points (17 possible points) and averaged
4.71 points. GAS appeared to detect meaningful change in more than 60% of
studies. CONCLUSIONS: GAS is a clinically useful tool for measuring progress
toward goals, but has not been utilized with a high level of methodological rigor
in research. Emphasis on reduced variation in administration and interpretation
will strengthen the utility of GAS for efficacy and program evaluation in future
research. Implications for rehabilitation Goal Attainment Scaling (GAS) can be
used across a diversity of interventions and diagnoses as an outcome measure in
pediatric rehabilitation. Careful consideration should be used in the study
design to standardize administration and scoring of GAS to strengthen the study.
Goal Attainment Scaling is responsive to change, and the tool appears to detect
meaningful change the majority of the time in pediatric rehabilitation.
PMID- 29954233
TI - Preeclampsia and the challenge of early prediction: reality or utopia? State of
art and critical review of literature.
AB - PURPOSE: The challenge to obtain improved predictive tools, able to identify
women destined to develop preeclampsia (PE), is raising the interest of
researchers for the attractive chance to allow for timely initiation of
prophylactic therapy, appropriate antenatal surveillance, and better-targeted
research into preventive interventions. We aimed to gather all the evidence
reported up to now in scientific literature relating to all prediction tests for
PE. MATERIALS AND METHODS: We searched articles on conventional literature
platforms from January 1952 to August 2016, using the terms "preeclampsia,"
"gestational preeclampsia," and "gestational hypertensive disorders" combined
with "predictive test" and "risk assessment." Abstracts/titles identified by the
search were screened by three investigators. RESULTS: The search identified 203
citations, of which 154 potentially relevant after the initial evaluation. Among
these studies, 20 full articles were excluded, therefore, 134 primary studies met
the criteria for inclusion and were analyzed. CONCLUSIONS: Current evidence
suggests that a combination of several features may provide the best predictive
accuracy for the identification of PE. Large-scale, multicenter, multiethnic,
prospective trials are required to propose an ideal combination of markers for
routine screening.
PMID- 29954235
TI - Extracting and Classifying Spatial Muscle Activation Patterns in Forearm Flexor
Muscles Using High-Density Electromyogram Recordings.
AB - The human hand is capable of producing versatile yet precise movements largely
owing to the complex neuromuscular systems that control our finger movement. This
study seeks to quantify the spatial activation patterns of the forearm flexor
muscles during individualized finger flexions. High-density (HD) surface
electromyogram (sEMG) signals of forearm flexor muscles were obtained, and
individual motor units were decomposed from the sEMG. Both macro-level spatial
patterns of EMG activity and micro-level motor unit distributions were used to
systematically characterize the forearm flexor activation patterns. Different
features capturing the spatial patterns were extracted, and the unique patterns
of forearm flexor activation were then quantified using pattern recognition
approaches. We found that the forearm flexor spatial activation during the ring
finger flexion was mostly distinct from other fingers, whereas the activation
patterns of the middle finger were least distinguishable. However, all the
different activation patterns can still be classified in high accuracy (94-100%)
using pattern recognition. Our findings indicate that the partial overlapping of
neural activation can limit accurate identification of specific finger movement
based on limited recordings and sEMG features, and that HD sEMG recordings
capturing detailed spatial activation patterns at both macro- and micro-levels
are needed.
PMID- 29954234
TI - Modified ARCA analogs providing enhanced translational properties of capped
mRNAs.
AB - Nowadays gene manipulation techniques ("DNA therapy") undergo progressive
development and become widely used in industry and medicine. Since new advances
in mRNA technologies are capable for obtaining particles with increased stability
and translational efficiency, RNA become an attractive alternative for
advancement of DNA therapy. For the past years studies have been conducted to
explore different modification in mRNA cap structure and its effect on RNA
properties. Recently we have shown that modification of the cap structure at the
N2 position of 7-methylguanosine leads to an enhancement in translation
inhibition. Currently, we have decided to exploit translational properties of
mRNA capped with the ARCA (anti-reversed cap) analogs modified within N2 position
of purine moiety s. We designed and synthesized three new dinucleotide cap
analogs and investigated them in the rabbit reticulocyte lysate (RRL) and the
human embryonic kidney derived HEK293 cell line, in vitro translational model
systems. The obtained data indicate that, in both translational assays, the cap
analogs synthesized by us when incorporated into mRNA improved its translational
properties compared to the ARCA capped transcripts. Furthermore, the introduced
modifications enhanced stability of the capped transcripts in HEK293 cells, which
become higher compared to that of the transcripts capped with regular cap or with
ARCA. Additionally one of the synthesized cap analogs revealed strong translation
inhibition potency in RRL system, with IC50 value 1.7 uM.
PMID- 29954236
TI - The histone chaperone ASF1 regulates the activation of ATM and DNA-PKcs in
response to DNA double-strand breaks.
AB - The Ataxia-telangiectasia mutated (ATM) kinase and the DNA-dependent protein
kinase catalytic subunit (DNA-PKcs) are activated by DNA double-strand breaks
(DSBs). These DSBs occur in the context of chromatin but how chromatin influences
the activation of these kinases is not known. Here we show that loss of the
replication-dependent chromatin assembly factors ASF1A/B or CAF-1 compromises ATM
activation, while augmenting DNA-PKcs activation, in response to DNA DSBs. Cells
deficient in ASF1A/B or CAF-1 exhibit reduced histone H4 lysine 16 acetylation
(H4K16ac), a histone mark known to promote ATM activation. ASF1A interacts with
the histone acetyl transferase, hMOF that mediates H4K16ac. ASF1A depletion leads
to increased recruitment of DNA-PKcs to DSBs. We propose normal chromatin
assembly and H4K16ac during DNA replication is required to regulate ATM and DNA
PKcs activity in response to the subsequent induction of DNA DSBs.
PMID- 29954237
TI - Corrigendum.
PMID- 29954238
TI - Monitoring dimeric status of IZUMO1 during the acrosome reaction in living
spermatozoon.
AB - The acrosome reaction (AR) is indispensable for successful spermatozoon-oocyte
fusion. Recent studies have indicated that sperm IZUMO1 gradually gathers in the
equatorial segment (EQ), which is the initiation site of sperm-egg fusion, after
the AR. In addition, by examining the binding process of oocytes and Izumo1
expressing cultured cells to reconstitute the early steps of fertilization, we
previously demonstrated that robust IZUMO1-dependent adhesion specifically occurs
at the contact site along with the dimerization of IZUMO1. However, when IZUMO1
dimerizes after the AR in living spermatozoon is unknown. Here, we report
dynamics of IZUMO1 dimerization during the AR in spermatozoa by combining
transgenic mice and time-lapse imaging using a set of bimolecular fluorescence
complementation (BiFC) probes. Surprisingly, dimeric IZUMO1 was already formed at
the acrosomal cap region before the AR and redistributed into the EQ after the
AR. We categorized the translocation of the dimer into two types: Type 1, the
near-simultaneous appearance of BiFC signals with IZUMO1-mCherry; and Type 2, the
delayed formation of dimer in the EQ. Those findings suggest that, before
encountering oocytes, spermatozoa are prepared to boost their affinity with JUNO.
PMID- 29954239
TI - MiR-146a promotes the asymmetric division and inhibits the self-renewal ability
of breast cancer stem-like cells via indirect upregulation of Let-7.
AB - MiR-146a could stimulate tumor growth or block tumor proliferation in systemic
malignancies, referring to the specific downstream targeted gene. However, its
roles in breast cancer stem-like cells (BrCSCs) are barely known. To dig out its
mechanistic functions, we explored the indicative roles of miR-146 in preclinical
study, regardless of the hormone receptor status, and the positive correlation
between miR-146 and better prognosis was proved, as its correlation to Let-7c
was. To uncover the implicated mechanisms, we first identified the suppressive
role of miR-146a in stem cells' renewal, which was achieved by promoting the
asymmetric division of BrCSCs. Let-7c was previously revealed with its
suppressive functions in stem-like cells expansion, and miR-146 was predicated
and successfully proved to bind to and degrade the 3'UTR of LIN28, a maturation
blocker of Let-7 family. Results further showed that miR-146a increased the Let
7c level through degrading LIN28, and LIN28 inhibition is required for miR-146a
induction of asymmetric stem cells' division. Moreover, Let-7 controlled Wnt
signaling pathway activity could be strengthened due to the miR146 inhibition of
H19, later of which was often activated in stem cells group with functional
existence of Wnt signaling. H19 itself in turn formed the positive feedback
regulation with Let-7. Our results suggested the miR-146a/LIN28/Wnt signaling
circle in restraining the symmetric cells division, which was specifically
referred to the controlling of the small circle of Let-7c and H19, and together,
this dual axis could help to prohibit the stem cells expansion.
PMID- 29954240
TI - EGFR activation induced Snail-dependent EMT and myc-dependent PD-L1 in human
salivary adenoid cystic carcinoma cells.
AB - Epithelial-to-mesenchymal transition (EMT) confers cancer cells the ability of
invasion and metastasis. However, how does EMT contribute to evasion of immune
surveillance is unclear, especially in salivary adenoid cystic carcinoma (SACC).
In this study, we investigated the molecular link between EGF-induced EMT and the
immune checkpoint ligand programmed death-ligand 1 (PD-L1) by immunoprecipitation
(IP) and Westernblot analysis. Cell migration and invasion activity was assayed
by transwell assay. Immunohistochemical (IHC) staining analysis was performed for
measurement of EMT markers and PD-L1 expression levels in tumor tissues. We found
that EGF-induced EGFR activation stabilized Snail expression and induced EMT in
SACC. Interestingly, EGFR activation induced simultaneously both EMT and PD-L1 in
SACC. Importantly, knockdown of Snail greatly suppressed EGF-induced EMT, but not
EGF-induced PD-L1 expression; whereas knockdown of c-Myc strongly repressed PD-L1
expression, but not snail expression and EMT. The molecular link is strongly
supported by robust correlations between the EMT markers and PD-L1 expression in
human cancer samples.These results suggest that EGFR activated EMT and PD-L1 via
two distinct mechanisms. EGFR activation induced EMT and PD-L1 expression in
SACC. Snail is required for EGF-induced EMT, but not PD-L1 expression; whereas c
Myc is required for EGFR-mediated PD-L1 upregulation but not EMT. Thus, targeting
activated EGFR may inhibit both EMT and PD-L1, which may potentiate the
therapeutic effect of PD-L1-based immunotherapy, especially in the malignant
subgroups of SACC patients with activated EGFR.
PMID- 29954241
TI - Clinical features of early-stage possible Behcet's disease patients with a
variant-type major organ involvement in Japan.
AB - BACKGROUND: Clinical data of patients with entro-, vasculo-, and neuro-variant
possible Behcet's disease (BD) based on Japanese criteria has not yet
comprehensively reported. METHODS: This ongoing nation-wide registration has been
carried out by the Japanese Ministry of Health, Labour and Welfare. The Ministry
asked physicians who diagnosed a patient with confirmed or possible BD to
register the patient data by filling out a registration form. The Ministry
provided us with the dataset after unlinkable anonymization. We analyzed 2003
2014 database generated from the early stage new cases. RESULTS: Among the 7950
analyzable cases, 694 (8.7%) had variant-type possible BD without satisfying
complete/incomplete criteria. Of the 694 patients, 479, 46, and 169 had entero-,
vasculo-, and neuro-variant possible BD, respectively. Out of these 694 patients,
35 (5.0%) and 154 (22.2%) satisfied the International Study Group criteria and
the International Criteria of BD, respectively. Entero-variant possible patients
rarely (1.8%) had ocular lesions. Patients with vasculo-variant possible BD were
featured by low genital ulceration risk (6.8%) and frequent positive HLA-B51
(60.0%). Neuro-variant possible BD was featured by high median age at
registration (48 year). Vasculo- (69.6%) and neuro-variant (68.6%) BD patients
showed clear male dominance. Epididymitis was very rare among variant-type
possible BD men. CONCLUSION: We analyzed 694 early-stage variant-type possible BD
cases. We believe the data from our study will contribute to further
international discussion regarding BD diagnostic criteria and clarification of
the clinical presentations of the Japanese variant-type possible BD patients.
PMID- 29954242
TI - Uterine artery flow velocity waveform (FVW) type and subednometrial vascularity
in recurrent pregnancy loss.
AB - PURPOSE: To assess the subendometrial and uterine artery blood flow and pattern
of the waveform of the uterine artery in cases of recurrent pregnancy loss
compared with normal controls. SUBJECTS AND METHODS: Fifty women with a history
of two or more successive pregnancy losses were investigated by Doppler
transvaginal ultrasound to assess the subendometrial blood flow resistance index
(RI), type of Doppler waveform of the uterine artery, and uterine artery
pulsatility index (PI) in the mid-luteal phase. Fifty normal women acted as
controls. RESULTS: Subendometrial blood flow RI and uterine artery PI were higher
in cases than controls. The majority of cases of recurrent pregnancy loss had a
waveform pattern of A, or loss of diastolic flow, whereas the controls were
mainly C wave. CONCLUSIONS: Some sort of endometrial and subendometrial ischemia
can be suggested in cases of recurrent pregnancy loss, waveform pattern of
uterine artery changes may be used to monitor changes in vascularity of
endometrium if vascular enhancers are given in such cases.
PMID- 29954243
TI - Evaluation of Meropenem Extended Versus Intermittent Infusion Dosing Protocol in
Critically Ill Patients.
AB - Extended infusion (EI) administration of beta-lactams can improve target
attainment in critically ill patients with altered
pharmacokinetics/pharmacodynamics. To optimize meropenem dosing in patients with
severe sepsis/septic shock, our Antimicrobial Stewardship Program implemented a
EI meropenem (EIM) protocol in an 18-bed Medical Intensive Care Unit in March
2014. In this retrospective study, we compared intensive care unit (ICU)
mortality and clinical response in patients who received meropenem for >=72 hours
administered per EIM protocol of 1 g over 3 hours every 8 hours versus
intermittent infusion (IIM) protocol of 500 mg over 30 minutes every 6 hours.
Age, weight, comorbidities, severity of illness, and vasopressor use were
comparable between groups (EIM protocol n = 52, IIM protocol n = 96). The IIM
protocol group had higher rates of renal dose adjustment at meropenem initiation.
Among 56 identified gram-negative (GN) pathogens, 94% had meropenem minimal
inhibitory concentration <=0.25 mg/L. The ICU mortality was lower (19 vs 37%; P =
.032) and clinical response was higher (83% vs 46%; P < .01) in the EIM protocol
versus IIM protocol group. Total vasopressor days were shorter (2 vs 3 days; P =
.038), and white blood cell normalization rate was higher (87% vs 51%; P < .01)
in the EIM protocol versus IIM protocol group. There was no difference in days of
mechanical ventilation, duration of therapy, and ICU stay. The IIM protocol was
also identified as an independent risk factor associated with ICU mortality
(hazard ratio: 3.653, 95% confidence interval: 1.689-7.981; P = .001) after
adjusting for Sequential Organ Failure Assessment score. In this cohort of
patients with severe sepsis/septic shock and highly susceptible GN pathogens,
there was improved mortality and clinical response in the EIM protocol group.
PMID- 29954244
TI - Direction-Specific Instability Poststroke Is Associated With Deficient Motor
Modules for Balance Control.
AB - Defective muscle coordination for balance recovery may contribute to stroke
survivors' propensity for falling. Thus, we investigated deficits in muscle
coordination for postural control and their association to body sway following
balance perturbations in people with stroke. Specifically, we compared the
automatic postural responses of 8 leg and trunk muscles recorded bilaterally in
unimpaired individuals and those with mild to moderate impairments after
unilateral supratentorial lesions (>6 months). These responses were elicited by
unexpected floor translations in 12 directions. We extracted motor modules (ie,
muscle synergies) for each leg using nonnegative matrix factorization. We also
determined the magnitude of perturbation-induced body sway using a single-link
inverted pendulum model. Whereas the number of motor modules for balance was not
affected by stroke, those formed by muscles with long latency responses were
replaced by atypically structured paretic motor modules (atypical muscle
groupings), which hints at direct cerebral involvement in long-latency feedback
responses. Other paretic motor modules had intact structure but were poorly
recruited, which is indicative of indirect cerebral control of balance.
Importantly, these paretic deficits were strongly associated with postural
instability in the preferred activation direction of the impaired motor modules.
Finally, these deficiencies were heterogeneously distributed across stroke
survivors with lesions in distinct locations, suggesting that different cerebral
substrates may contribute to balance control. In conclusion, muscle coordination
deficits in the paretic limb of stroke survivors result in direction-specific
postural instability, which highlights the importance of targeted interventions
to address patient-specific balance impairments.
PMID- 29954245
TI - Review of 16 cases of aneurysmal bone cyst in the proximal femur treated by
extended curettage and cryosurgery with reconstruction using autogenous
nonvascularized fibula graft.
AB - BACKGROUND: Aneurysmal bone cyst (ABC) is an aggressive benign lesion that may
sometimes be difficult to treat. Lesions that occur in the proximal femur require
to be addressed aggressively because of the high rate of local recurrence and the
risk of fracture. Few articles report the experience of management of ABC in the
proximal femur. This location presents a surgical challenge due to its anatomical
and biomechanical peculiarity. METHODS: We retrospectively reviewed 16 cases with
ABC in the proximal femur that were treated in our institution between 2005 and
2014, utilizing extended curettage and liquid nitrogen as adjuvant therapy and
reconstruction using nonvascularized autogenous fibular strut graft. The mean
follow-up period was 50.5 months. Five cases presented as recurrent cases, while
four cases presented with pathological fractures. RESULTS: The functional score
ranged from 70 to 90 on modified Musculoskeletal Tumor Society score with a mean
score of 81.25, which is considered to be excellent function. Time for graft
incorporation ranged from 10 to 12 weeks. One case got local recurrence, and one
case got early surgical site infection. CONCLUSIONS: Extended curettage and
cryotherapy represent a recommended approach for management of ABC in the
proximal femur with favorable results.
PMID- 29954246
TI - Effects of aging on memory strategies: a validation of the Portuguese version of
the Test of Memory Strategies.
AB - OBJECTIVE: Previous literature has shown that executive functions (EF) are
related to performance in memory tasks. The fact that there are no psychometric
tests that evaluate these two constructs simultaneously led a group of
researchers to develop the Test of Memory Strategies (TSM). Given the potential
importance of this instrument for neuropsychological evaluation, in this study,
we aimed to evaluate the psychometric properties of the TMS in Portuguese sample.
We also examined the effect of aging by exploring profiles of performance on the
TMS, comparing young and elderly healthy subjects. METHOD: Total of 135 healthy
participants were submitted to a neuropsychological assessment and were divided
into four age groups: a group of young adults (25-35 years) and three groups of
older individuals (aged 60-69 years, 70-79 years, and 80 or more years). RESULTS:
Findings supported the reliability of the TMS scores, based on analyses of
internal consistency. As expected, factor analysis of the TMS scores revealed
that the test yielded two factors, one capturing EF and the other memory.
Correlations with classic neuropsychological tests supported convergent and
discriminant validity of the TMS scores. The elderly groups presented more
difficulties in creating and mobilizing memory strategies when compared with a
younger group, after controlling for the influence of education, although both
groups presented increases in performance throughout the five TMS subscales.
CONCLUSIONS: The findings suggest that the TMS is an adequate measure to assess
memory and EF, simultaneously, presenting adequate psychometric properties for a
Portuguese sample.
PMID- 29954248
TI - Guidelines on statistics for researchers using laboratory animals: the
essentials.
AB - There is growing concern that the omnipresence of flawed statistics and the
deficient reproducibility that arises therefrom results in an unethical waste of
animals in research. The present review aims at providing guidelines in
biostatistics for researchers, based on observed frequent mistakes, misuses and
misconceptions as well as on the specificities of animal experimentation. Twelve
recommendations are formulated that cover sampling, sample size optimisation,
choice of statistical tests, understanding p-values and reporting results. The
objective is to expose important statistical issues that one should consider for
the correct design, execution and reporting of experiments.
PMID- 29954249
TI - Executive performance on the preschool executive task assessment in children with
sickle cell anemia and matched controls.
AB - : Executive deficits are commonly reported in children with sickle cell anemia.
Earlier identification of executive deficits would give more scope for
intervention, but this cognitive domain has not been routinely investigated due
to a lack of age-appropriate tasks normed for preschool children. In particular,
information relating to patient performance on an executive task that reflects an
everyday activity in the classroom could provide important insight and practical
recommendations for the classroom teacher at this key developmental juncture as
they enter the academic domain. The performance of 22 children with sickle cell
anemia was compared to 24 matched control children on the Preschool Executive
Task Assessment. Findings reveal that children with sickle cell anemia are
performing poorer than their matched peers on this multi-step assessment. In
particular, children with sickle cell anemia required more structured support to
shift focus after a completed step, as reflected by poorer scores in the
quantitative Sequencing and Completion domains. They also required more support
to stay on task, as seen by poorer ratings in the qualitative Distractibility
domain. ABBREVIATIONS: PETA: Preschool Executive Task Assessment; SCA: Sickle
Cell Anemia; EF: Executive Functioning.
PMID- 29954247
TI - The C-terminal p6 domain of the HIV-1 Pr55Gag precursor is required for specific
binding to the genomic RNA.
AB - The Pr55Gag precursor specifically selects the HIV-1 genomic RNA (gRNA) from a
large excess of cellular and partially or fully spliced viral RNAs and drives the
virus assembly at the plasma membrane. During these processes, the NC domain of
Pr55Gag interacts with the gRNA, while its C-terminal p6 domain binds cellular
and viral factors and orchestrates viral particle release. Gag?p6 is a truncated
form of Pr55Gag lacking the p6 domain usually used as a default surrogate for
wild type Pr55Gag for in vitro analysis. With recent advance in production of
full-length recombinant Pr55Gag, here, we tested whether the p6 domain also
contributes to the RNA binding specificity of Pr55Gag by systematically comparing
binding of Pr55Gag and Gag?p6 to a panel of viral and cellular RNAs.
Unexpectedly, our fluorescence data reveal that the p6 domain is absolutely
required for specific binding of Pr55Gag to the HIV-1 gRNA. Its deletion resulted
not only in a decreased affinity for gRNA, but also in an increased affinity for
spliced viral and cellular RNAs. In contrast Gag?p6 displayed a similar affinity
for all tested RNAs. Removal of the C-terminal His-tag from Pr55Gag and Gag?p6
uniformly increased the Kd values of the RNA-protein complexes by ~ 2.5 fold but
did not affect the binding specificities of these proteins. Altogether, our
results demonstrate a novel role of the p6 domain in the specificity of Pr55Gag
RNA interactions, and strongly suggest that the p6 domain contributes to the
discrimination of HIV-1 gRNA from cellular and spliced viral mRNAs, which is
necessary for its selective encapsidation.
PMID- 29954250
TI - The role of metabolic syndrome factors on cognition using latent variable
modeling: The neurocognitive study on aging.
AB - OBJECTIVE: Although metabolic syndrome (MetS) has been shown to increase the risk
of cognitive decline, it still remains unclear whether the risk is related to
MetS as a whole or its individual factors. The aim of the present study was to
explore whether MetS or its individual factors are associated with a lower
cognitive function in older adults in a Mediterranean population using latent
variable modeling. METHOD: Neurocognitive data from 640 Greek-Cypriot community
dwellers (female 59.1%), aged >=55 years, in good general health, were analyzed.
Assessments of anthropometric, blood pressure, fasting blood glucose, total
cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)
cholesterol, and triglyceride concentrations were carried out to investigate the
relationship between MetS factors and cognitive-linguistic outcomes of language,
executive function, and verbal episodic memory. RESULTS: When the MetS factors
were modeled as a single latent variable, they had small negative effects on
language and executive functions. Significance was not retained after age and
education were controlled for. When individual MetS factors along with age and
education were modeled as predictors, there were moderate negative age effects,
whereas education yielded strong positive effects on all three cognitive
outcomes. Weak significant negative coefficients of body mass index (BMI) and
blood glucose were found for executive functions, and a weak significant positive
effect of BMI was found for memory. Separate analysis by sex resulted in minor
but significant differences. CONCLUSION: BMI and blood glucose predicted
cognitive performance after controlling for age and education, and thus their
proper management should be taken into account for maintaining cognitive health
in aging. Findings also demonstrate the importance of education and age in
studies investigating cardiometabolic risk factors and cognitive function, as
well as the need for further research on the effects of sex.
PMID- 29954253
TI - Two Cases and a Review of Graft-Versus-Host Disease and the Role of Hepatitis C
Treatment in Liver Transplant Patients.
AB - Graft-versus-host disease (GvHD) is a rare but fatal complication after solid
organ transplantation arising in 1% to 2% of cases. We report 2 cases of GvHD
after orthotopic liver transplantation. Both patients had a history of hepatitis
C virus (HCV) infection prior to transplantation. Both cases presented between 1
and 4 months after transplantation with rash, pancytopenia, and/or diarrhea. Our
second case also developed oral and ocular manifestations after liver
transplantation, which are more commonly described after stem cell
transplantation. Diagnosis in both cases was made by clinical presentation in
conjunction with histopathology and flow cytometry. Both patients were treated by
increasing immunosuppression with tacrolimus and high-dose steroids. Response to
treatment differed based on the degree of pancytopenia. Our case report is
distinguished by several factors such as the context of GvHD presentation and the
role of HCV treatment. Diagnosis of GvHD is difficult and often delayed due to
nonspecific presentation that overlaps with other conditions. Furthermore, the
relation between HCV treatment and potential initiation of GvHD in solid organ
transplant patients is unclear.
PMID- 29954252
TI - Comparison of isometric triceps brachii force measurement in different elbow
positions.
AB - PURPOSE: Objective and reliable force measurement is necessary to monitor the
rehabilitation after triceps brachii pathology, injuries, and posterior approach
based surgery. It is unclear at which amount of extension the triceps is best
tested and if comparison to the uninjured sided is reliable. This study aims to
identify the most reliable elbow position at which elbow extension force is
measured using a dynamometer. Furthermore, it aims to compare the extension
strength of the dominant arm with that of the nondominant arm. METHODS: Isometric
elbow extension force of the dominant and nondominant arms of healthy subjects
was measured. The measurements were taken in three sequences per arm in 0, 30,
60, 90, and 120 degrees of flexion. A subgroup repeated the measurements to
analyze test-retest reliability using intraclass correlation. RESULTS: We
included a total of 176 volunteers. The repeated measures analysis of variance
for within-subject effect showed the lowest variation coefficient at 30 degrees
of flexion. Extension forces showed a mean difference of 3.2-6.9 N in advantage
of the dominant arm, resulting in ratios from 1.05 to 1.09. Learning curve
analysis showed that during the first session in dominant and nondominant arms,
less forces were exerted. CONCLUSION: The most reliable isometric triceps brachii
muscle strength measurement was at 30 degrees of flexion of the elbow.
Considering the learning curve, a first tryout session for both arms is
indicated. Then, a second measurement suffices as no further learning curve is
observed.
PMID- 29954251
TI - Functional role of circular RNAs in cancer development and progression.
AB - Circular RNAs (circRNAs) are a large class of endogenously expressed non-coding
RNAs formed by covalently closed loops through back-splicing. High throughput
sequencing technologies have identified thousands of circRNAs with high sequence
conservation and cell type specific expression in eukaryotes. CircRNAs play
multiple important roles in cellular physiology functioning as miRNA sponges,
transcriptional regulators, RBP binding molecules, templates for protein
translation, and immune regulators. In a clinical context, circRNAs expression is
correlated with patient's clinicopathological features in cancers including
breast, liver, gastric, colorectal, and lung cancer. Additionally, distinct
properties of circRNAs, such as high stability, exonuclease resistance, and
existence in body fluids, show promising role for circRNAs as molecular
biomarkers for tumor diagnosis, non-invasive monitoring, prognosis, and
therapeutic intervention. Therefore, it is critical to further understand the
molecular mechanism underlying circRNAs interaction in tumors and the recent
progress of this RNA species in cancer development. In this review, we provide a
detailed description of biological functions, molecular role of circRNAs in
different cancers, and its potential role as biomarkers in a clinical context.
PMID- 29954254
TI - A Preliminary Study: Human Fibroid Stro-1+/CD44+ Stem Cells Isolated From Uterine
Fibroids Demonstrate Decreased DNA Repair and Genomic Integrity Compared to
Adjacent Myometrial Stro-1+/CD44+ Cells.
AB - CONTEXT: Although uterine fibroids (UFs) continue to place a major burden on
female reproductive health, the mechanisms behind their origin remain
undetermined. Normal myometrial stem cells may be transformed into tumor
initiating stem cells, causing UFs, due to unknown causes of somatic mutations in
MED12, found in up to 85% of sporadically formed UFs. It is well established in
other tumor types that defective DNA repair increases the risk of such
tumorigenic somatic mutations, mechanisms not yet studied in UFs. OBJECTIVE: To
examine the putative cause(s) of this stem cell transformation, we analyzed DNA
repair within stem cells from human UFs compared to those from adjacent
myometrium to determine whether DNA repair in fibroid stem cells is compromised.
DESIGN: Human fibroid (F) and adjacent myometrial (Myo) stem cells were isolated
from fresh tissues, and gene expression relating to DNA repair was analyzed.
Fibroid stem cells differentially expressed DNA repair genes related to DNA
double- (DSBs) and single-strand breaks. DNA damage was measured using alkaline
comet assay. Additionally, DNA DSBs were induced in these stem cells and DNA DSB
repair evaluated (1) by determining changes in phosphorylation of DNA DSB-related
proteins and (2) by determining differences in gamma-H2AX foci formation and
relative DNA repair protein RAD50 expression. RESULTS: Overall, F stem cells
demonstrated increased DNA damage and altered DNA repair gene expression and
signaling, suggesting that human F stem cells demonstrate impaired DNA repair.
CONCLUSIONS: Compromised F stem cell DNA repair may contribute to further
mutagenesis and, consequently, further growth and propagation of UF tumors.
PMID- 29954255
TI - Visual Illusions: Nothing to Lose but Your Chains-A Reply to Oliver Braddick.
PMID- 29954256
TI - Compression therapy for uncomplicated varicose veins - Too little for too much?
PMID- 29954257
TI - Combination of Octopus and Periscope Techniques for the Management of Visceral
Branches From Type V Thoracoabdominal Aortic Aneurysm: A Case Report.
AB - PURPOSE:: To describe an endovascular technique combining the octopus and
periscope techniques for the treatment of a patient with type V thoracoabdominal
aortic aneurysm in order to protect the patient's visceral circulation. CASE
REPORT:: An 84-year-old male patient was hospitalized for type V thoracoabdominal
aortic aneurysm involving celiac axis, superior mesenteric artery, and both renal
arteries. The patient's aneurysm was successfully treated by combining the
octopus technique and periscope techniques. The 1-year follow-up computed
tomography angiography showed that the endograft and the branches were patent.
The gutters had thrombosed with no signs of endoleak. No spinal cord ischemia or
impairment of the renal function was observed during the follow-up. CONCLUSIONS::
This case is an example of the successful usage of the combined octopus and
periscope techniques in protecting the renovisceral arteries arising from a type
V thoracoabdominal aortic aneurysm; this combined technique might be applicable
in carefully selected patients.
PMID- 29954258
TI - Effects of Statin Treatment on Outcomes after Traumatic Brain Injury.
AB - Neuroprotective treatments that have shown promise in reducing secondary injury
and improving recovery in animal models of traumatic brain injury (TBI) have not
been found effective to date in humans. One reason may be the delay after injury
in initiating treatment. Statin medications are among the promising
neuroprotective agents in animal models, and their presence in the bloodstream of
many individuals at the time of injury might optimize their clinical impact. This
observational study conducted by a subset of centers participating in the
National Institute on Disability, Independent Living, and Rehabilitation Research
(NIDILRR)-funded TBI Model System program sought to examine the effects of taking
statin medication at the time injury on functional outcomes. Participants >50
years of age were prospectively enrolled during patient rehabilitation.
Demographic data, cardiovascular history, and brain injury history were obtained
through chart abstraction and interview. Prescription medication use in the year
prior to enrollment was determined from a national pharmacy search service.
Propensity scoring was used to create 49 pairs of participants who were well
matched on demographic and clinical attributes but discordant for statin use. The
treated and untreated participants did not differ on initial Glasgow Coma Score,
time until commands were followed, duration of post-traumatic amnesia, or
Functional Independence Measure (FIM) scores at rehabilitation admission,
discharge, or 1 year post-injury, or on acute or rehabilitation hospital lengths
of stay. Evidence of greater and lesser statin compliance was not associated with
outcome. This study did not provide support for a clinically important benefit of
statin use at the time of moderate to severe TBI.
PMID- 29954259
TI - Hypertension Self-Management Perspectives From African American Older Adults.
AB - African Americans are disproportionately impacted by hypertension, suffering
earlier onset and greater severity of the disease, and premature cardiovascular
mortality, than the general population. Managing hypertension is an unending
concern for African American older adults. A better understanding of the self
management preferences of this vulnerable population will lead to the enhanced
design of culturally acceptable interventions. This descriptive study examined
focus group participants' perspectives on engaging in hypertension self
management activities with the goal of developing a co-created intervention. This
study was part of a mixed methods study for which audio- and graphically-recorded
focus groups were conducted with community-dwelling African American older adults
( N = 31) diagnosed with hypertension. The majority of the participants were
women (87%); the mean age was 72 years ( SD = 7.53). Themes derived from data
analyses centered on primary stressors of communication, healthy eating, and
sleep related to blood pressure self-management. Based on these, the researchers
co-created educational interventions.
PMID- 29954260
TI - Overcoming public health risks to staff during the management of waste from
healthcare facilities.
AB - Purpose The management of public health risks is a key focus for the European
Union. One of the key factors that has been shown to pose a public health risk is
that of the management of needles from healthcare facilities. The paper aims to
discuss this issue. Design/methodology/approach Using audits of two case study
hospitals based in northern Italy, this study sought to examine the key factors
that resulted in needle stick injuries amongst staff and suggest measures to
minimise these risks. Findings The number of needle stick injuries was influenced
by various key factors including the time period during the year, the length of
time employed, the location within the site, staff category and working hours.
Practical implications Suggestions for overcoming the risk factors, including
redesigning working patterns, staff training and awareness building, and the use
of safety-engineered devices are outlined. Originality/value This study examined
the incidence of needle stick injuries amongst healthcare staff in two Italian
hospitals, which was lower than in other countries due to various factors,
including recapping of needles not being allowed, the introduction of self
retractable needles and awareness campaigns about the correct disposal procedures
of potentially infectious waste.
PMID- 29954261
TI - Public awareness of adverse drug reaction medical safety.
AB - Purpose The purpose of this paper is to contribute to the literature by assessing
factors that typically engender adverse drug reactions (ADRs) jeopardizing
medical safety. These factors are population knowledge, clarity in disclosure of
the risks inhering ADRs and ADRs incidence. It seeks to minimize negative effect
by early identification of drug reactions. Design/methodology/approach On the one
hand, the study employs a model that shows relationships between various factors,
and on the other hand, ADRs medical safety in the public healthcare sector.
Findings Clarity of consultancy services in public healthcare significantly
impact ADR medical safety. Population and healthcare provider education on ADRs
medical safety are necessities. Implementation of an ADR reporting system in
every healthcare institute is essential. This helps service providers to give a
clear and accurate information to patients. It also makes patients more aware of
consequences of ADRs. Research limitations/implications Time, place and sampling
method are found to be the main study limitations. Researchers should take into
their consideration the significant relationships between the factors and ADRs
medical safety to improve level of awareness in the healthcare public sector.
Practical implications Ways to improve ADR medical safety in healthcare sector
are underscored. Healthcare service providers and professionals need to take into
account the stipulated study factors in order to improve medical safety and
reduce unnecessary medical costs. Originality/value Very few studies have been
conducted on this topic; most of those that have been conducted were undertaken
in western countries. This study assesses the level of healthcare safety in the
country and suggests mechanisms to elevate that level.
PMID- 29954262
TI - The success of strategic planning in health care organizations of Iran.
AB - Purpose Although strategic planning promised to boost organizational performance,
many health care managers found it difficult to implement it successfully. The
purpose of this paper is to investigate the success of strategic planning in
health care organizations of Iran. Design/methodology/approach This descriptive
and cross-sectional study was conducted in 2016 using a valid and reliable
questionnaire completed by 99 health care managers in Tehran province, Iran.
Findings Strategic planning was positively related to organizational performance
including employees' and patients' satisfaction and organizational productivity.
However, strategic planning was moderately successful in enhancing organizational
performance of Iranian health care organizations (score of 2.84 out of 5). The
most and least success was observed in the planning and employee management
constructs of organizational performance. Process management, organizational
culture and customer management constructs had the most effect on the success of
strategic plans in health care organizations. Practical implications Strategic
planning is effective and provides a clear focused direction for health care
organizations. Understanding the success factors of strategic planning would
enable managers to develop more effective methods for developing, implementing
and evaluating strategic plans in health care organizations. Originality/value
This paper highlights the relationship between strategic planning and
organizational performance and offers suggestions on how to develop and implement
strategic plans to achieve higher organizational performance.
PMID- 29954263
TI - Registered nurses' use of computerised decision support in medication reviews.
AB - Purpose The purpose of this paper is to explore the implications of registered
nurses' (RNs) use of a computerized decision support system (CDSS) in medication
reviews. Design/methodology/approach The paper employs a quasi-experimental, one
group pre-test/post-test design with three- and six-month follow-ups subsequent
to the introduction of a CDSS. In total, 11 RNs initiated and prepared a total of
54 medication reviews. The outcome measures were the number of drug-related
problems (DRPs) as reported by the CDSS and the RNs, respectively, the RNs' views
on the CDSS, and changes in the quality of drug treatment. Findings The CDSS
significantly indicated more DRPs than the RNs did, such as potential adverse
drug reactions (ADRs). The RNs detected additional problems, outside the scope of
the CDSS, such as lack of adherence. They considered the CDSS beneficial and
wanted to continue using it. Only minor changes were found in the quality of drug
treatments, with no significant changes in the drug-specific quality indicators
(e.g. inappropriate drugs). However, the use of renally excreted drugs in reduced
renal function decreased. Practical implications The RNs' use of a CDSS in
medication reviews is of value in detecting potential ADRs and interactions. Yet,
in order to have an impact on outcomes in the quality of drug treatment, further
measures are needed. These may involve development of inter-professional
collaboration, such as established procedures for the implementation of
medication reviews, including the use of CDSS. Originality/value This is, to the
best of the authors' knowledge, the first study to explore the implications of
medication reviews, initiated and prepared by RNs who use a CDSS. The paper adds
further insight into the RNs' role in relation to quality of drug treatments.
PMID- 29954264
TI - Implementation of the surgical safety checklist in hospitals of Iran; operating
room personnel's attitude, awareness and acceptance.
AB - Purpose The WHO Surgical Safety Checklist (SSC) has improved patient safety
effectively. Despite the known benefits of applying the checklist before surgery,
its implementation is less than universal in practice. The purpose of this paper
is to determine the operating room personnel's attitude, their awareness and
knowledge of the SSC, and to evaluate staff acceptance of the SSC (including
personal beliefs). Design/methodology/approach This cross-sectional study was
conducted in eight tertiary general hospitals in Tehran, Iran. Some 145 operating
room personnel (surgeons, anaesthetists and nurses) were selected for the study.
Data collection was carried out via a validated questionnaire in three parts
which included socio-demographic, attitude, awareness and acceptance. Data were
then analysed using the Kruskal-Wallis and chi2 statistical test. Findings Out of
the 145 participants in the study, 92 per cent were aware of the existence of the
SSC and 73.9 per cent of them were aware of the objectives of SSC. Overall, the
attitude to SSC was positive. The attitude of surgeons was positive towards the
impact of the SSC on safety and teamwork. Surgeons were significantly more
sensitive to the barriers of SSC application compared to nurses and anaesthetists
( p=0.046). Among the three groups, nurses had the highest level of support for
SSC ( p=0.001). Practical implications Despite high acceptance of the checklist
among staff, there is still a gap in knowledge about when exactly the checklist
should be used. Therefore, involvement of all surgical team members to complete
the checklist process, support of senior managers, on-going education and
training and consideration of the barriers to its implementation are all key
areas that need to be taken into account. Originality/value This is the first
research to examine the operating room personnel's attitude, awareness and
acceptance about SSC in Iranian hospitals. The outcomes of this study provide
documentation and possible justification for effective establishment of SSC in
Iran and other countries.
PMID- 29954265
TI - Structural quality of healthcare facilities in India.
AB - Purpose Although India has a number of health issues, the healthcare facilities
in India are insufficient due to poor quality of care. The purpose of this paper
is to examine the factors affecting the structural quality of healthcare
facilities in India. Design/methodology/approach This study used the medical
facility data from the India Human Development Survey-II, 2011-2012 (ICPSR 36151)
( n=4,218). Logistic regression was conducted to predict structural quality of
healthcare facilities. Findings The results suggest that it is difficult to have
all standard resources available at health care facilities in India.
Surprisingly, having a drinking water source inside the health facility appears
to be an indicator of poor structural quality of health care facilities. Having a
water source inside a health care facility is associated with not having a
separate exam room and not having a sink to wash hands. A higher registration fee
was associated with good structural quality and with having a separate exam room
and having a sink to wash hands. Originality/value This study shows the
complexity of providing quality health care to the poor, particularly in
developing countries. Research on quality of healthcare facilities in India is
needed to improve the health of the population. Little research has been done on
the factors influencing the structural quality of the healthcare facilities in
India. This study is an important contribution to the current knowledge of
structural healthcare facility standards and its influences in India.
PMID- 29954266
TI - Performance evaluation of a coagulation laboratory using Sigma metrics.
AB - Purpose Two-thirds of medical decisions are based on laboratory test results.
Therefore, laboratories should practice strict quality control (QC) measures.
Traditional QC processes may not accurately reflect the magnitude of errors in
clinical laboratories. Six Sigma is a statistical tool which provides opportunity
to assess performance at the highest level of excellence. The purpose of this
paper is to evaluate performance of the coagulation laboratory utilizing Sigma
metrics as the highest level of quality. Design/methodology/approach Quality
indicators of the coagulation laboratory from January 1, 2009, to December 31,
2015, were evaluated. These QIs were categorized into pre-analytical, analytical
and post-analytical. Relative frequencies of errors were calculated and converted
to Sigma scale to determine the extent of control over each process. The Sigma
level of 4 was considered optimal performance. Findings During the study period,
a total of 474,655 specimens were received and 890,535 analyses were performed.
These include 831,760 (93.4 percent) routine and 58,775 (6.6 percent) special
tests. Stat reporting was requested for 166,921 (18.7 percent). Of 7,535,146
total opportunities (sum of the total opportunities for all indicators), a total
of 4,005 errors were detected. There were 2,350 (58.7 percent) pre-analytical, 11
(0.3 percent) analytical and 1,644 (41 percent) post-analytical errors. Average
Sigma value obtained was 4.8 with 12 (80 percent) indicators achieving a Sigma
value of 4. Three (20 percent) low-performance indicators were: unacceptable
proficiency testing (3.8), failure to inform critical results (3.6) and delays in
stat reporting (3.9). Practical implications This study shows that a small number
of errors can decrease Sigma value to below acceptability limits. If clinical
laboratories start using Sigma metrics for monitoring their performance, they can
identify gaps in their performance more readily and hence can improve their
performance and patient safety. Social implications This study provides an
opportunity for the laboratorians to choose and set world-class goals while
assessing their performance. Originality/value To the best of the authors'
knowledge and belief, this study is the first of its kind that has utilized Sigma
metrics as a QC tool for monitoring performance of a coagulation laboratory.
PMID- 29954267
TI - Ensuring quality immediate discharge letters from mental health.
AB - Purpose Immediate discharge letters (IDLs) from the mental health unit at Forth
Valley Royal Hospital are vital in ensuring safe patient transfer to primary
care. The purpose of this paper is to develop a standardised list of information
that should be included in all IDLs, and to assess its use in practice.
Design/methodology/approach Three audit cycles analysed IDLs over two-week
periods for their inclusion of the standardised list. The data were assessed
qualitatively. Findings Baseline measurement showed 48.7 per cent of discharges
had a brief reason for admission, 15.4 per cent included a description of the
patient's progress during inpatient admission, 35.9 per cent had medication
alterations included and 23.1 per cent included follow-up arrangements. Following
a series of interventions, analysis of subsequent IDLs demonstrated that 76.2 per
cent of discharges had a brief reason for admission, 76.2 per cent included a
description of the patient's progress during inpatient admission, 76.2 per cent
had medication alterations included and 71.4 per cent included follow-up
arrangements. Originality/value The standardised list developed will ensure
quality communication and safe patient transfer to primary care; the application
of this list was effective and cost neutral.
PMID- 29954268
TI - Relationship marketing strategy.
AB - Purpose The purpose of this paper is to explore how strategies are put in place
to formulate policies regarding the introduction and implementation of
relationship marketing (RM) in the health sector, and how RM strategies are
designed as part of the curricula for the training of prospective health
professionals in Ghana. Design/methodology/approach Data were gathered using
interviews and documentary review. A purposive sampling technique was used to
recruit policy makers and health educationists in Accra for in-depth interviews.
Qualitative interviews were analysed using framework analysis. Findings The
findings revealed that, currently, there is no policy framework on RM in the
health sector nor included in the curricula of health training institutions in
the country. Research limitations/implications Due to limited time and funding
constraints, the study could not include many policy makers, educationists,
health providers, facilities and regions outside the Greater Accra region of
Ghana. This means that the authors missed out on useful insights from other
relevant policy makers/educationists who would have added to the knowledge that
this study contributes. There were still some areas that this study could not
cover, including the lack of an exploration of the perceptions of health
providers and patients. Practical implications Evidence from the current research
provides the basis for scaling up of a similar study to the whole country to
address the perennial RM or quality of care/patient satisfaction issues
persisting in health facilities in the country. The outcome of this large-scale
study would help to confirm the findings of the current study on the adoption and
incorporation of RM into both policy framework and curricula of health training
institutions in Ghana. The findings would culminate in the preparation and
utilisation of guidelines on RM for client-centred service delivery in the health
sector of the country. Social implications This paper argues that RM orientation
could enable health professionals to improve upon their healthcare service
performance and quality of care so as to enhance patient satisfaction.
Originality/value The study recommends that RM should be adopted by health policy
makers and designers of curricula for health training institutions.
PMID- 29954269
TI - Doctors attitudes towards medication errors at 2002 & 2015.
AB - Purpose The purpose of this paper is to explore the attitudes and beliefs of
doctors towards medication error reporting following 15 years of a national
patient safety agenda. Design/methodology/approach This is a qualitative
descriptive study utilising semi-structured interviews. A group of ten doctors of
different disciplines shared their attitudes and beliefs about medication error
reporting. Using thematic content analysis, findings were reflected upon those
collected by the same author of a similar study 13 years before (2002). Findings
Five key themes were identified: lack of incident feedback, non-user-friendly
incident reporting systems, supportive cultures, electronic prescribing and time
pressures. Despite more positive responses to the benefits of medication error
reporting in 2015 compared to 2002, doctors at both times expressed a reluctance
to use the hospital's incident reporting system, labelling it time consuming and
non-user-friendly. A more supportive environment, however, where error had been
made was thought to exist compared to 2002. The role of the pharmacist was
highlighted as critical in reducing medication error with the introduction of
electronic prescribing being pivotal in 2015. Originality/value To the authors'
knowledge, this is the first study to compare doctors' attitudes on medication
errors following a period of time of increased patient safety awareness. The
results suggest that error reporting today is largely more positive and
organisations are more supportive than in 2002. Despite a change from paper to
electronic methods, there is a continuing need to improve the efficacy of
incident reporting systems and ensure an open, supportive environment for
clinicians.
PMID- 29954270
TI - Factors affecting sentinel events in hospital emergency department: a qualitative
study.
AB - Purpose A sentinel event is an unexpected occurrence resulting in death or
serious physical or psychological injury or the risk thereof. The purpose of this
paper is to investigate the influencing factors of sentinel events in the
emergency department of a military hospital in Tehran to find out some of the
effective solutions. Design/methodology/approach In this qualitative study with
content analysis approach, 20 hospital healthcare personnel participated as
participants from the fields of medicine and nursing. Purposive random sampling
and semi-structured interviews were used for data collection. Atlas.ti software
version 5.2 was used for data analysis. Findings Four themes and 32 subthemes
were identified by numerous revisions and combining the codes. The four main
themes of sentinel events were: causes, incidence barriers, cause prevention
solutions, and barriers' improvement solutions. Moreover, these main factors were
related to these issues: staff and patients' education, communication,
assessment, patients and their companions, employee rights, leadership, care
continuum, human factors, physical environment, information management and
medication use. Some solutions were also suggested according to these factors and
a policy was recommended. Practical implications Hospital managers and
authorities should try to find the main causes of sentinel events by periodical
analysis to find ways to prevent them in the future, using logical and reasonable
solutions. Originality/value This study confirms that strategies to reduce the
sentinel events in emergency departments should focus on empowerment of all
staff.
PMID- 29954271
TI - Supply chain partnership assessment of a diabetes clinic.
AB - Purpose Diabetes is one of the major healthcare challenges in India. The chronic
nature of the disease makes the lifetime cost of the treatment exorbitantly high.
The medicine cost contributes a major size of expense in diabetes management. To
make healthcare available to poorest of the poor, it is imperative to control the
rising cost of diabetes treatment. The earlier research works done in this area
focuses more on inventory management techniques to control the cost of
healthcare. Less interest is shown in the role of better supply chain partnership
(SCP) in reducing the cost of procurement of medicine. The purpose of this paper
is to develop and use the SCP assessment framework for a diabetes clinic. The
approach is generalized enough to be adopted for other similar organization.
Design/methodology/approach This paper adopts self-assessment criteria of the
European Foundation for Quality Management (EFQM) business excellence model for
analysis of SCP in the supply chain of a private diabetes clinic in Varanasi. The
paper uses analytic hierarchy process (AHP) method for calculation of weights of
criteria. Findings The EFQM-based framework can be adopted as easy-to-use tool to
make an objective assessment of the SCP. The proposed model in the study is a
balanced model between enablers and results, which includes multiple assessment
dimensions. The supply chain performance score of the diabetes clinic under study
was found as the Tool Pusher, which means the effort in direction of SCP is not
too good. The organization needs to clearly define the SCP goal and analyze the
results to identify the gap areas. Originality/value The study is first of its
kind and contributes to the literature by providing non-prescriptive and easy-to
use SCP assessment framework, for chronic disease care. The case study approach
provides a procedure for the healthcare organization willing to adopt this
approach.
PMID- 29954272
TI - Implementation of an in-hospital stroke simulation protocol.
AB - Purpose A major component of hospital stroke care involves prompt identification
of stroke in admitted patients. Delays in recognizing stroke symptoms and
initiating treatment for in-hospital stroke can adversely impact patient
outcomes. This quality improvement intervention used simulation together with a
traditional lecture to instruct nurses at a university hospital about a new
stroke protocol being implemented to increase rapid recognition of stroke and
meet Joint Commission National Hospital Inpatient Quality Measures. The paper
aims to discuss these issues. Design/methodology/approach In total, 86 registered
nurses from the neurology and cardiology units attended a lecture and
participated in a simulation scenario with a standardized patient exhibiting
stroke symptoms. Participants completed a ten-item pre-test to measure their
knowledge of stroke care prior to the lecture; they repeated the test pre
simulation and once again post-simulation to evaluate changes in knowledge.
Findings Overall mean stroke knowledge scores increased significantly from pre
lecture to pre-simulation, and from pre-simulation to post-simulation. Simulation
plus lecture was more effective than lecture alone in increasing knowledge about
hospital stroke protocol despite assigned unit (cardiology or neurology), years
of experience, or previous exposure to simulation. Research
limitations/implications All eligible nurses who agreed to participate received
training, making it impossible to compare improvements in knowledge to those who
did not receive the training. Originality/value A diverse array of nursing
professionals and their patients may benefit from simulation training. This
quality improvement intervention provides a feasible model for establishing new
care protocols in a hospital setting.
PMID- 29954273
TI - Enabling continuous learning and quality improvement in health care.
AB - Purpose The purpose of this paper is to examine how the design and implementation
of learning models for performance management can foster continuous learning and
quality improvement within a publicly funded, multi-site community hospital
organization. Design/methodology/approach Niagara Health's patient flow
performance management system, a learning model, was studied over a 20-month
period. A descriptive case study design guided the analysis of qualitative
observational data and its synthesis with organizational learning theory
literature. Emerging from this analysis were four propositions to inform the
implementation of learning models and future research. Findings This performance
management system was observed to enable: ongoing performance-related knowledge
exchange by creating opportunities for routine social interaction; collective
recognition and understanding of practice and performance patterns; relationship
building, learning for improvement, and "higher order" learning through dialogue
facilitated using humble inquiry; and, alignment of quality improvement efforts
to organizational strategic objectives through a multi-level feedback/feed
forward communication structure. Research limitations/implications The single
organization and descriptive study design may limit the generalizability of the
findings and introduce confirmation bias. Future research should more
comprehensively evaluate the impact of learning models on organizational learning
processes and performance outcomes. Practical implications This study offers
novel insight which may inform the design and implementation of learning models
for performance management within and beyond the study site. Originality/value
Few studies have examined the mechanics of performance management systems in
relation to organizational learning theory and research. Broader adoption of
learning models may be key to the development of continuously learning and
improving health systems.
PMID- 29954274
TI - Nursing staff perceptions regarding the clinical audit tool used for relicensing
inspections within eThekwini private hospitals in South Africa.
AB - Purpose The purpose of this paper is to assess nursing staff perceptions
regarding the clinical audit tool used for relicensing inspections within private
hospitals in eThekwini district. Design/methodology/approach An exploratory
sequential mixed method research design was used with a qualitative first phase
involving a total population of 40 nurse managers through purposive sampling.
Nurse managers ( n=24) were interviewed. This was followed by a quantitative
phase in which a structured questionnaire was administered to nurses ( n=270) who
were randomly sampled for the study from ( n=4) hospitals. Documentation review,
a third phase was used to corroborate the findings of the first two phases of the
study. Findings The results of the study showed that the participants perceptions
of the selected private hospitals in eThekwini district is that they have not
fully implemented the approach to practice standards and healthcare audits in
relation to three clinical domains of the National Core Standards and the Batho
Pele principles. These findings were significant and denoted the need for a
standardised clinical audit tool for private hospitals in eThekwini district.
Research limitations/implications This study was confined to an independent group
of hospitals and the findings may not be suitable for generalising across all
private hospitals in eThekwini district. Originality/value These findings led to
the development of a clinical audit tool with measurements representing elements
of care that are critical to the provision of safe, quality health care services.
PMID- 29954275
TI - Quality assurance in segmental neck of femur fractures.
AB - Purpose The purpose of this paper is to report a rare case of segmental neck of
femur fracture (SNoFF) and highlight its quality assurance and governance
implications with respect to national guidelines, care pathways and best practice
tariff. Design/methodology/approach Case report of an SNoFF in a 67-year-old
woman treated at a district general hospital (DGH) was used in this study.
Findings SNoFF required additional implants that delayed the surgery by five
days. The authors were unable to adhere to the British Orthopaedic Association
standards for trauma and Scottish Inter-Collegiate Guidelines Network
recommendations which indicate that all neck of femur fractures (NoFFs) be fixed
within 48 h. Though the patient was discharged without any untoward event and had
an uneventful recovery, this case led us to introspect and learn how best to
avoid such an incident from repeating again. Research limitations/implications
This case led to an overhaul of NoFF and trauma services. The local logistics was
restructured to procure "Trochanteric grip plates" within 24 h to provide
mandated quality of care in an effort towards improving patient
experience/outcomes. Originality/value SNoFF are rare injuries and its diagnosis
is either delayed or missed in at least 20 per cent of the cases on initial
evaluation. The non-availability of additional implants readily on the shelf
coupled with lack of a trauma bed at the tertiary centre resulted in an
unacceptable delay from admission to definitive surgery. The authors recommend
that all DGHs have a mechanism/emergency procurement procedure system in place to
obtain the required instrumentation kits rapidly through a sharing scheme with
regional hospitals or through implant vendor to avoid unacceptable delays to
surgery.
PMID- 29954276
TI - Who reads editorials any more?
PMID- 29954277
TI - Workplace violence prevention standardization using lean principles across a
healthcare network.
AB - Purpose The purpose of this paper is to describe the process used to standardize
a Workplace Violence Prevention Program (WVPP) within a five-hospital healthcare
system in Veterans Health Administration (VHA). Design/methodology/approach A
description of the lean process improvement principles, used to bring the WVPP
into compliance with Occupational Safety and Health Administration (OSHA) and
other agencies through streamlining/standardizing processes. Findings There was
significant standardization in both the threat assessment and education arms of
the WVPP. Compliance with all major US Department of Labor OSHA requirements, as
well as substantial time savings, were realized as part of this process
improvement. Originality/value VHA is leading the way in inter/multidisciplinary
assessment and mitigation of workplace violence, however, there are significant
competing demands on staff time. This first ever use of lean principles to
streamline processes around workplace violence prevention freed up clinician time
for care while improving internal and external customer satisfaction,
representing a major step forward in workplace violence risk mitigation.
PMID- 29954278
TI - Service quality and satisfaction in healthcare sector of Pakistan- the patients'
expectations.
AB - Purpose The purpose of this paper is to assess the influence of patients'
expectations from healthcare service quality on their satisfaction with nursing
in public and private hospitals of Pakistan. Design/methodology/approach Data (
n=456) were collected from three public sector hospitals and three private sector
hospitals of Lahore, the capital of Pakistan's most populous province. Male and
female patients who have experience of both sectors were surveyed using a self
administered questionnaire developed using the original SERVQUAL approach. Data
were analyzed using the statistical techniques and the Laplace criterion.
Findings This paper attempts to explain degree of influences of five service
quality constructs (empathy, responsiveness, tangibility, reliability and
assurance) on Pakistani patients' expectations from the private and public sector
hospitals and thus patient satisfaction. Further, this work can offer several
intuitions into the effect of five constructs of service quality on patients'
expectations of healthcare service quality and patient satisfaction with the
service providers/nursing. The results reveal that the patient satisfaction is
most strongly related to empathy in public sector and to responsiveness in
private sector. Research limitations/implications In light of the previous
studies and the current research findings, the study anticipates no apparently
significant improvement in healthcare sector of Pakistan in near future
considering various factors discussed in the study. The study will also help the
service providers and the policy makers in understanding the deteriorating
situation of the Pakistani healthcare sector and will guide them in identifying
the areas by improving which not only the healthcare service quality in the
country can be improved but also the image of healthcare sector among the masses
and competitiveness of the healthcare sector can be enhanced. Originality/value
The value of the study rests in its critical analysis of the current status of
the healthcare sector of Pakistan with a view to suggest the areas that need to
be worked on by the service providers and policy makers. Also, the study tries to
settle a controversy within Pakistani healthcare literature concerning the
question that who is producing more satisfied patients: private hospitals or
their public counterparts?
PMID- 29954279
TI - Increased serum leptin levels are associated with metabolic syndrome and carotid
intima media thickness in premenopausal systemic lupus erythematosus patients
without clinical atherosclerotic vascular events.
AB - Aim To assess subclinical atherosclerosis and the role of inflammatory mediators,
vascular endothelial cell activation markers and adipocytokines in systemic lupus
erythematosus (SLE) in the presence or absence of metabolic syndrome (MetS).
Methods We studied 66 premenopausal female SLE patients (20 with MetS) and 28
female healthy controls (HCs) without history of cardiovascular disease (CVD).
Subclinical atherosclerosis was screened by measuring carotid intima media
thickness (CIMT). Serum levels of high sensitivity C-reactive protein (hs-CRP),
tumour necrosis factor alpha (TNFalpha), interleukin 6 (IL-6), soluble
intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin, leptin and
visfatin were measured. Results The mean age of MetS+SLE, MetS- and HC were 38.3
+/- 6.7, 32.7 +/- 9.3 and 29.9 +/- 5.6 years, respectively. The mean disease
duration, SLICC (Systemic Lupus International Collaborating Clinics damage index)
and Systemic Lupus Erythematosus Disease Activity Index scores were 74.8 +/- 54.9
months, 0.16 +/- 0.48 and 1.18 +/- 1.5, respectively, and were similar between
MetS+and MetS- SLE patients. CIMT values were higher in both MetS+ and MetS- SLE
patients than HCs ( p < 0.001). sICAM-1 and erythrocyte sedimentation rate levels
were higher in both MetS+ and MetS- SLE patients than HCs ( p < 0.001; p = 0.002,
p = 0.001). The SLE MetS+ group had higher CIMT values than SLE MetS- (right: p =
0.003; left: p = 0.025). Leptin levels and homeostatic model assessment (HOMA)
scores were significantly higher in SLE MetS+ than SLE MetS- ( p = 0.018; p =
0.04). Leptin and CRP levels and body mass index, SLICC and HOMA scores were
correlated with CIMT values (right: p = 0.03, p < 0.001, p < 0.001, p = 0.026 and
p < 0.001, and left: p = 0.028, p = 0.03, p = 0.003, p = 0.002 and p = 0.025).
Conclusions In premenopausal women with SLE without a history of CVD, CIMT values
were increased and related to MetS. Leptin was increased in patients with MetS
and correlated with CIMT values.
PMID- 29954280
TI - Syncope caused by complete heart block and ventricular arrhythmia as early
manifestation of systemic lupus erythematosus in a pregnant patient: a case
report.
AB - Systemic lupus erythematosus (SLE) can affect all heart structures including the
conduction system, with either reversible or permanent derangement. However, only
a few cases of adult SLE and complete atrioventricular (AV) block have been
reported. We describe a young pregnant woman who initially presented with
complete AV block on electrocardiography before the diagnosis of SLE. Syncope
subsequently developed during the postpartum period due to frequent nonsustained
polymorphic ventricular tachycardia, suggesting lupus myocarditis. The
ventricular arrhythmia was successfully treated by intravenous corticosteroids,
lidocaine and implantation of a permanent pacemaker. This may represent the first
report of complete AV block with polymorphic ventricular tachycardia, which was
identified before the other clinical features of SLE fully manifested. SLE should
be considered if a patient presents with complete AV block without other clinical
features. It may warn for early diagnosis and appropriate treatment of SLE
including lupus-related heart disease.
PMID- 29954281
TI - Treating lupus patients with antimalarials: analysis of safety profile in a
single-center cohort.
AB - This longitudinal retrospective study aims at describing the safety profile and
the reasons for discontinuation of antimalarials in patients with systemic lupus
erythematosus (SLE) and discoid lupus erythematosus (DLE), focusing on ocular
toxicity. We analyzed the clinical data of 845 SLE and DLE patients; 59% of them
were taking antimalarials: 1.4% chloroquine (CQ), 88.5% hydroxychloroquine (HCQ)
and 10.1% both. The mean therapy duration was 82.5 +/- 77.4 months. At least one
side effect was reported by 19.4% of patients, leading to temporary or permanent
withdrawal in 9.1% and 10.3% of cases, respectively; 19.3% of patients
experienced side effects with HCQ and 8.6% with CQ. In 55.1% of cases, the
adverse event was mild or moderate. Ophthalmological alterations were reported by
8.5% but were confirmed by the ophthalmological examination in 5.5% of cases.
Retinal alterations were associated with age, disease duration and duration of
the antimalarial therapy, but not to drug dose and comorbidities or lupus
nephritis. This is the largest monocentric longitudinal study confirming the good
safety profile of antimalarials in DLE and SLE patients. The main adverse events
during the therapy were mild or moderate, but maculopathy-reported in a low
percentage of patients-remains the main cause of treatment withdrawal.
PMID- 29954282
TI - Depression and medication nonadherence in childhood-onset systemic lupus
erythematosus.
AB - Objectives Depression and medication nonadherence are important in managing
chronic diseases, but little is known about these factors in childhood-onset
systemic lupus erythematosus (cSLE). The objectives of this cross-sectional study
were to estimate prevalence of depression and medication nonadherence, describe
demographic and disease characteristics associated with depression and medication
nonadherence, and evaluate the association between depression and medication
nonadherence in cSLE patients. Methods Patients with cSLE ( n = 51) completed
validated screening questionnaires to identify depression and medication
nonadherence, Patient Health Questionnaire-9 and Medication Adherence Self-Report
Inventory, respectively. Demographic and disease characteristics were obtained
via chart abstraction, and compared between groups of depression or medication
nonadherence status. A multivariable linear regression model adjusting for
propensity scores was conducted to evaluate the association between depression
and medication nonadherence. Results The prevalence of a positive depression
screen was 58.8%, and seven patients reported suicidal ideation (13.7%). The
prevalence of self-reported medication nonadherence was 19.7%. No statistically
significant differences for demographic and disease characteristics were found
between patients with a positive vs. negative depression screen. Patients
reporting medication nonadherence were more likely to have longer disease
duration (4.8 vs. 2.6 years, p = 0.035). As the severity of depression symptoms
increased, the degree of medication nonadherence also increased (beta = -1.89; p
= 0.011). Conclusions The prevalence of depression and medication nonadherence is
high in cSLE, and these factors have a direct relationship. Interventions that
better recognize and treat depression and increase rates of medication adherence
are needed to improve outcomes in cSLE.
PMID- 29954283
TI - Efficacy of discontinuing risedronate for patients with systemic lupus
erythematosus: a prospective study.
AB - Objective The objective of this study is to investigate the effectiveness of
discontinuation of risedronate for patients with systemic lupus erythematosus
(SLE) treated with glucocorticoid (GC). Methods The participants were patients
with SLE treated with prednisolone (PSL) >= 2 mg/day and risedronate for at least
three years. Lumbar spine and total hip bone mineral density (BMD) measurements
were taken at baseline and 24 and 48 weeks after discontinuation of risedronate,
and bone turnover markers were evaluated at baseline, 12, 24, 36, and 48 weeks.
Results A total of 36 patients were enrolled, 25 of whom discontinued
risedronate. The mean age was 46.8 +/- 11.2 years, and 23 were female. The mean
duration of GC treatment was 14.8 +/- 11.4 years, the mean dose of PSL was 7.8 +/
3.9 mg/day, and the mean duration of risedronate was 5.8 +/- 2.4 years.
Seventeen patients showed decreased lumbar spine BMD at 48 weeks after
discontinuation of risedronate, with a mean lumbar spine lumbar decrease of 1.42%
+/- 3.20% ( p = 0.034); 17 patients (71%) showed a decreased total hip BMD at 48
weeks after discontinuation of risedronate, with a mean total hip BMD decrease of
0.99% +/- 2.10% ( p = 0.021). Serum tartrate-resistant acid phosphatase 5b (TRACP
5b) >= 309 mU/dl at baseline was a risk factor for decreased total hip BMD at 48
weeks compared with serum TRACP-5b < 309 mU/dl (56% vs 0%, p = 0.0098). One
patient developed a clinical fracture of the lumbar spine at 20 weeks.
Conclusions Discontinuation of risedronate treatment in patients with SLE who had
received GC therapy led to decreases in lumbar spine and total hip BMD,
particularly in patients with high baseline serum TRACP-5b levels.
PMID- 29954284
TI - Plasma levels of beta2-microglobulin are associated with atherosclerosis in
patients with systemic lupus erythematosus: a cross-sectional cohort study.
AB - Objective The objective of this paper is to examine the association between
plasma levels of beta2-microglobulin (beta2MG), a protein previously associated
with atherosclerosis, and the presence of carotid plaque (CP) or coronary artery
calcium (CAC) in a cross-sectional cohort study of patients with systemic lupus
erythematosus (SLE). Methods Patients with SLE were enrolled between June 2013
and May 2014. The presence of CP and CAC was assessed with ultrasonography and
computed tomography scan, respectively. The presence of CP or CAC in the SLE
patients was analyzed with respect to plasma levels of beta2MG and renal function
expressed as the estimated glomerular filtration rate (eGFR). Results The study
cohort consisted of 147 patients, 89% women and 95% Caucasians. The median age
was 46 (range: 21-75) years with a median disease duration of 14 years. CP and
CAC was observed in 29 (20%) and 57 (39%) of patients, respectively. CP or CAC
was seen in 62 (42%) patients and was associated with the highest quartile of
plasma beta2MG in patients with eGFR >= 90 ml/min/1.73 m2; OR = 18 (95% CI: 1.7
181). beta2MG adjusted for eGFR was also associated with presence of CP or CAC in
the total cohort. The exclusion of 25 patients with a prior history of
cardiovascular disease did not change the observed associations. Conclusion In
this study, we found significant associations between imaging markers of
atherosclerosis and high plasma levels of plasma beta2MG. These data suggest that
beta2MG is a candidate for further study as a biomarker for atherosclerosis in
SLE.
PMID- 29954285
TI - Beyond comanaged inpatient care to community integration: Factors leading to
surgical delay in hip fractures and their associated outcomes.
AB - PURPOSE: Early surgery for older adults with hip fracture has been shown to
improve outcomes. We aim to study the factors contributing to delay in surgery
(defined as surgery performed more than 48 h after admission) and its associated
outcomes in a tertiary hospital in Singapore with an integrated hip fracture
program. METHODS: This is a prospective cohort study of hip fracture patients
aged more than 60 years over 1 year. We collected data on demographics, premorbid
mobility and functional status, time to surgery, postoperative complications, and
inhospital mortality. Mortality data and functional performance were reviewed at
1 year. RESULTS: High American Society of Anaesthesiologists score independently
predicted delay in surgery (odd ratio (OR) = 9.52, 95% confidence interval (CI):
1.69-53.68). Delayed surgery was significantly associated with longer length of
stay (median 12.8 days with interquartile range (IQR) 9.7-17.6 days vs. 8.35 days
with IQR 5.9-10.9 days, p < 0.01). Surgery within 48 h significantly reduced
functional decline (Modified Barthel Index change -3.89 +/- 17.23 vs. -9.29 +/-
20.30, p = 0.01) and 1-year mortality (3.5% vs. 9.3%, p = 0.03). Surgical delay
was an independent risk factor for early postoperative complications (OR = 3.21,
95% CI: 1.21-8.49), and patients were significantly less likely to return to
premorbid mobility at 1 year (OR = 0.62, 95% CI: 0.39-0.97). CONCLUSIONS: Delayed
hip fracture surgery in older adults is associated with worse short- and long
term outcomes, including early postoperative complications and poorer functional
recovery.
PMID- 29954286
TI - ProBAPred: Inferring protein-protein binding affinity by incorporating protein
sequence and structural features.
AB - Protein-protein binding interaction is the most prevalent biological activity
that mediates a great variety of biological processes. The increasing
availability of experimental data of protein-protein interaction allows a
systematic construction of protein-protein interaction networks, significantly
contributing to a better understanding of protein functions and their roles in
cellular pathways and human diseases. Compared to well-established classification
for protein-protein interactions (PPIs), limited work has been conducted for
estimating protein-protein binding free energy, which can provide informative
real-value regression models for characterizing the protein-protein binding
affinity. In this study, we propose a novel ensemble computational framework,
termed ProBAPred (Protein-protein Binding Affinity Predictor), for quantitative
estimation of protein-protein binding affinity. A large number of sequence and
structural features, including physical-chemical properties, binding energy and
conformation annotations, were collected and calculated from currently available
protein binding complex datasets and the literature. Feature selection based on
the WEKA package was performed to identify and characterize the most informative
and contributing feature subsets. Experiments on the independent test showed that
our ensemble method achieved the lowest Mean Absolute Error (MAE; 1.657[Formula:
see text]kcal/mol) and the second highest correlation coefficient ([Formula: see
text]), compared with the existing methods. The datasets and source codes of
ProBAPred, and the supplementary materials in this study can be downloaded at
http://lightning.med.monash.edu/probapred/ for academic use. We anticipate that
the developed ProBAPred regression models can facilitate computational
characterization and experimental studies of protein-protein binding affinity.
PMID- 29954287
TI - New variable selection strategy for analysis of high-dimensional DNA methylation
data.
AB - In genetic association studies, regularization methods are often used due to
their computational efficiency for analysis of high-dimensional genomic data. DNA
methylation data generated from Infinium HumanMethylation450 BeadChip Kit have a
group structure where an individual gene consists of multiple Cytosine-phosphate
Guanine (CpG) sites. Consequently, group-based regularization can precisely
detect outcome-related CpG sites. Representative examples are sparse group lasso
(SGL) and network-based regularization. The former is powerful when most of the
CpG sites within the same gene are associated with a phenotype outcome. In
contrast, the latter is preferred when only a few of the CpG sites within the
same gene are related to the outcome. In this paper, we propose new variable
selection strategy based on a selection probability that measures selection
frequency of individual variables selected by both SGL and network-based
regularization. In extensive simulation study, we demonstrated that the proposed
strategy can show relatively outstanding selection performance under any
situation, compared with both SGL and network-based regularization. Also, we
applied the proposed strategy to identify differentially methylated CpG sites and
their corresponding genes from ovarian cancer data.
PMID- 29954288
TI - Succinate aggravates NAFLD progression to liver cancer on the onset of obesity:
An in silico model.
AB - The incidence and prevalence of nonalcoholic fatty liver disease (NAFLD) have
been increasing to epidemic proportions around the world. NAFLD, a chronic liver
disease that affects the nondrinkers, is mainly associated with steatohepatitis
and cirrhosis. The progression of NAFLD associated with obesity increases the
risk of liver cancer, a disease with poor outcomes and limited therapeutic
options. In order to investigate the underlying cellular dynamics leading to
NAFLD progression towards cancer on the onset of obesity, we have integrated
human hepatocyte pathway with hypoxia-inducible factor1-[Formula: see text] (HIF1
[Formula: see text]) signaling pathway using state space model based on classical
control theory. Modified Michaelis-Menten equation and mass action law have been
used to define flux vectors of the proposed model. We have incorporated feedback
inhibition/activation and allosteric effects into the simulink-based model. The
values of kinetic constants have been taken from the literature. It is found that
on the onset of obesity, HIF1-[Formula: see text]-induced proteins stabilize
approximately 62 times that in the case of a normal cell. Consequently, the HIF1
[Formula: see text]-induced proteins enhance the enzymatic activities of
hexokinase (HK), phosphofructo kinase (PFK), lactate dehydrogenase (LDH), and
pyruvate dehydrogenase (PDH), which induce Warburg effect promoting an
environment suitable for cancer cells.
PMID- 29954289
TI - Accuracy of thoracic pedicle screw placement using freehand technique and
triggered EMG in adolescent idiopathic scoliosis: Is it different between concave
and convex side?
AB - PURPOSE: To evaluate and compare the accuracy of the placement of thoracic
pedicle screws between concave and convex side curve using freehand technique and
triggered electromyogram (EMG). METHODS: Three-hundred sixty eight thoracic
pedicle screws were included for the evaluation of accuracy from postoperative
computed tomography (CT) scans in 24 patients with adolescent idiopathic
scoliosis with a mean follow-up of 27 months (range 24-58 months). All screws had
stimulation thresholds greater than 6 mA. We divided the screws into two groups:
(1) group A: concave side curve-254 screws (2) group B: convex side curve-114
screws. RESULTS: The mean age at surgery was 12.8 years (range 11-17 years). The
preoperative Cobb angle was 57.5 degrees (range 50-75 degrees ). There were 41
total breaches (medial = 21, lateral = 20, p = 0.66) with an overall incidence of
11.1%. The overall breach rate did not attain statistically significant
difference (group A = 11.8%, group B = 9.6%, p = 0.59). The rate of medial
breaches was also similar for both concave and convex side (group A = 6.1%, group
B = 5.9%, p > 0.05). No postoperative neurological or vascular complications were
noted in both groups. CONCLUSION: Thoracic pedicle screw placement using both
freehand technique and triggered EMG for adolescent idiopathic scoliosis surgery
is safe and reliable. The overall accuracy rate is 88.9% with similar breaches on
the concave and convex side on postoperative CT scans.
PMID- 29954290
TI - Do what you say and say what you are going to do: A preliminary meta-analysis of
client change and sustain talk subtypes in motivational interviewing.
AB - OBJECTIVE: This meta-analysis examines the predictive validity of client change
language subtypes in motivational interviewing (MI) sessions addressing addictive
behavior change. METHOD: A systematic review identified k = 13 primary studies,
contributing 16 MI conditions (N = 1556). The pooled correlation coefficient was
used to assess the significance, direction, and strength of seven language
subtypes (i.e., reason, desire, need, ability, commitment, taking steps, and
other) by three valences (i.e., frequency positive or change talk, frequency
negative or sustain talk, and proportion change talk) and their relationship to
subsequent engagement in addictive behavior. RESULTS: For frequency measures,
more sustain talk related to reason, desire, ability, and other were associated
with more addictive behavior at follow up. Other change talk was associated with
MI outcomes but in an unexpected direction (i.e., more addictive behavior).
Proportion measures showed more proportion change talk-reason and -other
statements were associated with less addictive behavior at follow up. Sensitivity
analyses indicated some heterogeneity and instability of effect sizes, but no
evidence of publication bias. CONCLUSIONS: This preliminary meta-analysis
suggests that aggregate measures of change and sustain talk are comprised of
statement subtypes that are not equally meaningful in predicting outcome
following MI for addictive behavior change.
PMID- 29954291
TI - On Dr Dick Climie and Dr Jack Thomas, and the genesis of chemical-clinical
pharmacology in Australian anaesthesia research.
AB - Pharmacokinetic and pharmacodynamic research is regularly reported in most
contemporary anaesthesia-oriented journals. This sub-specialty area of
pharmacology grew rapidly from the 1960s as various essential concepts and tools
laboratory analysis of drug/metabolite concentrations in biofluids, physiological
signal collection, and methods for analysing/presenting relevant pharmacokinetic
and pharmacodynamic data-started coming together. For Australia, such research
began in Sydney in the mid-1960s with collaboration between anaesthetist Dr C.R.
Climie (1923-2013) at the Royal Hospital for Women and medicinal chemist Dr J.
Thomas OAM (1928-2017), and was achieved through a succession of postgraduate
research student projects in the Department of Pharmacy of The University of
Sydney, initially supervised by Dr Thomas. These consisted of studies concerned
with the systemic absorption and placental transmission of drugs being used in
parturients. By the late 1960s, Sydney anaesthetists Drs G.J. Long and C.A.
Shanks (1936-1998) were also participating, and the projects were becoming more
complex, including studies of the metabolism of local anaesthetics and other
drugs by mothers and neonates. Between the mid-1970s and early-1980s, with
additional anaesthetists, postgraduate research students and their academic
supervisors participating, the projects focussed mainly on the pharmacokinetics
and pharmacodynamics of neuromuscular blocking agents. This form of chemical
clinical-pharmacologically-based anaesthesia-oriented research that started in
Sydney with the collaboration of Drs Climie and Thomas led to many challenging
higher degree projects for pharmaceutical scientists, and access to unprecedented
research capabilities for anaesthetists. Most significantly, it established a
permanent place for multidisciplinary pharmacokinetic- and pharmacodynamic-based
research within Australian academic departments of anaesthesia.
PMID- 29954292
TI - Origin of the word 'anesthesiology': Mathias J. Seifert, MD.
AB - The word 'anesthesiology' was coined in 1902 by Mathias J. Seifert, MD, of
Chicago, Illinois. Seifert was an accomplished musician before he commenced his
medical training. After graduation in 1901 he held academic positions in medicine
and gynaecology before being appointed Professor of Physical Diagnosis and
Anesthesiology at the College of Dentistry, University of Illinois. He was later
appointed Professor of Surgery at the Chicago Hospital College of Medicine.
PMID- 29954293
TI - Professor Ross Holland: The Special Committee Investigating Deaths Under
Anaesthesia (SCIDUA) and his other contributions to anaesthesia.
AB - As a young anaesthetic trainee in 1959 Ross Holland persuaded the Minister of
Health in NSW, Australia, to establish SCIDUA, which by law required compulsory
reporting for all deaths occurring during anaesthesia or up to 24 hours after
cessation of the anaesthetic. The committee was multidisciplinary and, most
importantly, had statutory privilege so that no discussions or findings were able
to be subpoenaed for other legal investigations or case law. Holland was the
foundation secretary of SCIDUA and later Chair. Apart from three years in the
1980s when there were political issues with legal privilege, the committee has
met monthly and still meets. Holland was a major figure in antipodean
anaesthesia, setting up in 1978 the clinical department at Westmead Hospital
Sydney, then in 1987 becoming the foundation Professor to the Department of
Anaesthesiology at the University of Hong Kong, and in 1990 foundation Professor
and Chair, Department of Anaesthesia and Intensive Care at the University of
Newcastle, NSW. Holland had strong historical interests and was responsible for
founding the Society for the Preservation of Artefacts of Surgery and Medicine
(SPASM) and its associated museum. He also served an important term as Dean of
the Faculty of Anaesthetists, Royal Australasian College of Surgeons prior to
that Faculty becoming independent as the Australian and New Zealand College of
Anaesthetists (ANZCA). Professor Holland received many accolades for these
activities during his life, which are noted. It is fitting to recognise his
seminal contributions to patient safety over more than 50 years.
PMID- 29954294
TI - Unusual partnerships: The Corfe-McMurdie anaesthetic inhaler of 1918 and the 2nd
Australian Casualty Clearing Station.
AB - This World War 1 ether/chloroform vaporiser-inhaler was designed by and made for
Captain Anstruther John Corfe by Private Eric Aspinall McMurdie, both of the 2nd
Australian Casualty Clearing Station (ACCS), Australian Army Medical Corps
(AAMC). It has a plaque attached labelled 25 May 1918. It is a perfect example of
the ingenuity forced by the realities of war, and is one of the unique pieces in
the Harry Daly Museum at the Australian Society of Anaesthetists (ASA)
headquarters in Sydney, Australia. While serving in Blendecques, France, Private
McMurdie ingeniously fashioned this vaporiser from discarded items he found on
the battlefield. These included Horlick's Malted Milk bottles, on which he etched
measurements for ether and chloroform, and a spent brass artillery shell, which
made the heating component of the inhaler. The 2nd ACCS triaged and operated on
thousands of troops, and this inhaler is a reflection of the skills and
innovative expertise of the staff of the 2nd ACCS which included X-rays to
localise foreign bodies, and locally made splints and apparatus to treat trench
foot.
PMID- 29954295
TI - Genesis of the College of Intensive Care Medicine of Australia and New Zealand.
AB - In 2009 the College of Intensive Care Medicine (CICM) of Australia and New
Zealand was inaugurated in Melbourne, Australia. This College now regulates the
education, training and accreditation for specialist intensivists for Australia
and New Zealand. CICM origins started in 1975 with the formation of the Section
of Intensive Care of the Faculty of Anaesthetists, Royal Australasian College of
Surgeons (RACS), which moved through intermediary stages as the Faculty of
Intensive Care, Australian and New Zealand College of Anaesthetists (ANZCA) when
that College was formed from the former Faculty of Anaesthetists RACS, and then
the Joint Faculty of Intensive Care Medicine (ANZCA and the Royal Australasian
College of Physicians [RACP]), until becoming completely independent as CICM in
2010. There was a period of about 40-50 years evolution from the first formations
of intensive care units in Australia and New Zealand, and discussions by the
personnel staffing those units amongst themselves and with Members of the Board
of the Faculty of Anaesthetists RACS, to the formation of the Section of
Intensive Care, then through two intermediary Faculties of Intensive Care
Medicine, to the final independent formation of the College of Intensive Care
Medicine of Australia and New Zealand in 2010.
PMID- 29954296
TI - Millikin & Lawley version of John Snow's chloroform inhaler.
PMID- 29954297
TI - John Snow's "On the Inhalation of the Vapour of Ether in Surgical Operations".
PMID- 29954298
TI - Report on the 9th International Symposium on the History of Anesthesia, Boston,
USA: 24-28 October 2017.
PMID- 29954300
TI - Priorities for preventing a concentrated HIV epidemic among Aboriginal and Torres
Strait Islander Australians.
PMID- 29954301
TI - A novel, culturally appropriate approach to weight management in Aboriginal and
Torres Strait Islander people.
PMID- 29954303
TI - My mother, Ngandi.
PMID- 29954302
TI - Regulating consumer use of transcranial direct current stimulation devices.
PMID- 29954304
TI - Reversible pancytopenia caused by severe copper deficiency in a patient with
Wilson disease.
PMID- 29954305
TI - Managing the disconnect between scientific discovery and its translation into
practice.
PMID- 29954306
TI - Acute medicine for busy physicians.
PMID- 29954307
TI - Indigenous health: one gap is closed.
PMID- 29954308
TI - The Medical Journal of Australia endorses the Uluru Statement.
PMID- 29954309
TI - Multimorbidity in Aboriginal and non-Aboriginal people.
PMID- 29954310
TI - Closing the gap in cardiovascular risk for Aboriginal and Torres Strait Islander
Australians.
PMID- 29954311
TI - Multimorbidity among Aboriginal people in New South Wales contributes
significantly to their higher mortality.
AB - OBJECTIVES: To compare the prevalence of multimorbidity and its impact on
mortality among Aboriginal and non-Aboriginal Australians who had been
hospitalised in New South Wales in the previous 10 years. DESIGN, SETTING AND
PARTICIPANTS: Cohort study analysis of linked NSW hospital (Admitted Patient Data
Collection) and mortality data for 5 437 018 New South Wales residents with an
admission to a NSW hospital between 1 March 2003 and 1 March 2013, and alive at 1
March 2013. MAIN OUTCOME MEASURES: Admissions for 30 morbidities during the 10
year study period were identified. The primary outcome was the presence or
absence of multimorbidity during the 10-year lookback period; the secondary
outcome was mortality in the 12 months from 1 March 2013 to 1 March 2014.
RESULTS: 31.5% of Aboriginal patients had at least one morbidity and 16.1% had
two or more, compared with 25.0% and 12.1% of non-Aboriginal patients. After
adjusting for age, sex, and socio-economic status, the prevalence of
multimorbidity among Aboriginal people was 2.59 times that for non-Aboriginal
people (95% CI, 2.55-2.62). The prevalence of multimorbidity was higher among
Aboriginal people in all age groups, in younger age groups because of the higher
prevalence of mental morbidities, and from age 60 because of physical
morbidities. The age-, sex- and socio-economic status-adjusted hazard of one-year
mortality (Aboriginal v non-Aboriginal Australians) was 2.43 (95% CI, 2.24-2.62),
and 1.51 (95% CI, 1.39-1.63) after also adjusting for morbidity count.
CONCLUSIONS: The prevalence of multimorbidity was higher among Aboriginal than
non-Aboriginal patients, and this difference accounted for much of the difference
in mortality between the two groups. Evidence-based interventions for reducing
multimorbidity among Aboriginal and Torres Strait Islander Australians must be a
priority.
PMID- 29954312
TI - Agreement between diagnoses of otitis media by audiologists and otolaryngologists
in Aboriginal Australian children.
AB - OBJECTIVES: To determine the degree of agreement of diagnoses by audiologists and
otolaryngologists of otitis media (OM) in Aboriginal children. DESIGN: Cross
sectional study of agreement between diagnoses. SETTING: Study of Environment on
Aboriginal Resilience and Child Health (SEARCH), a prospective cohort study of
Aboriginal children attending four Aboriginal Community Controlled Health
Services in New South Wales (three metropolitan, one regional) during 2008-2012.
PARTICIPANTS: 1310 of 1669 SEARCH participants (78.5%; mean age, 7.0 years; SD,
4.4 years) were assessed and received a diagnosis from one of five experienced
audiologists. Test results (but not case histories) were forwarded to one of
three otolaryngologists for blinded independent assessment. MAIN OUTCOME
MEASURES: Agreement of OM diagnoses by audiologists and otolaryngologists at ear
and child levels; correctness of audiologist diagnoses (otolaryngologist
diagnosis as reference). RESULTS: Paired diagnoses by audiologists and
otolaryngologists were available for 863 children at the child level and 1775
ears (989 children) at the ear level. Otolaryngologists diagnosed OM in 251
children (29.1%), including 11 (1.3%) with tympanic membrane perforation, and in
396 ears (22.3%), including 12 (0.7%) with perforation. Agreement between
audiologists and otolaryngologists for OM at the ear level was 92.2% (kappa =
0.78; 95% CI, 0.74-0.82), and at the child level 91.7% (kappa = 0.81; 95% CI,
0.77-0.85). No otolaryngologist-diagnosed perforation was missed by audiologists.
Among 1000 children triaged by an audiologist, there would be 45 false positives
and 30 false negatives when compared with assessments by an otolaryngologist,
with no missed perforations. CONCLUSIONS: There was substantial agreement between
audiologists' and otolaryngologists' diagnoses of OM in a high prevalence
population of Aboriginal children. In settings with limited access to
otolaryngologists, audiologists may appropriately triage children and select
those requiring specialist review.
PMID- 29954313
TI - Royal Australian and New Zealand College of Psychiatrists clinical practice
guidelines for mood disorders: major depression summary.
PMID- 29954314
TI - Selecting medical students: we need to assess more than academic excellence.
PMID- 29954315
TI - Brilliant career recognised.
PMID- 29954316
TI - MICOP: Maximal information coefficient-based oscillation prediction to detect
biological rhythms in proteomics data.
AB - BACKGROUND: Circadian rhythms comprise oscillating molecular interactions, the
disruption of the homeostasis of which would cause various disorders. To
understand this phenomenon systematically, an accurate technique to identify
oscillating molecules among omics datasets must be developed; however, this is
still impeded by many difficulties, such as experimental noise and attenuated
amplitude. RESULTS: To address these issues, we developed a new algorithm named
Maximal Information Coefficient-based Oscillation Prediction (MICOP), a sine
curve-matching method. The performance of MICOP in labeling oscillation or non
oscillation was compared with four reported methods using Mathews correlation
coefficient (MCC) values. The numerical experiments were performed with time
series data with (1) mimicking of molecular oscillation decay, (2) high noise and
low sampling frequency and (3) one-cycle data. The first experiment revealed that
MICOP could accurately identify the rhythmicity of decaying molecular oscillation
(MCC > 0.7). The second experiment revealed that MICOP was robust against high
level noise (MCC > 0.8) even upon the use of low-sampling-frequency data. The
third experiment revealed that MICOP could accurately identify the rhythmicity of
noisy one-cycle data (MCC > 0.8). As an application, we utilized MICOP to analyze
time-series proteome data of mouse liver. MICOP identified that novel oscillating
candidates numbered 14 and 30 for C57BL/6 and C57BL/6 J, respectively.
CONCLUSIONS: In this paper, we presented MICOP, which is an MIC-based algorithm,
for predicting periodic patterns in large-scale time-resolved protein expression
profiles. The performance test using artificially generated simulation data
revealed that the performance of MICOP for decaying data was superior to that of
the existing widely used methods. It can reveal novel findings from time-series
data and may contribute to biologically significant results. This study suggests
that MICOP is an ideal approach for detecting and characterizing oscillations in
time-resolved omics data sets.
PMID- 29954317
TI - Establishment and comparison of air-liquid interface culture systems for primary
and immortalized swine tracheal epithelial cells.
AB - BACKGROUND: Air-liquid interface (Ali) systems allow the establishment of a
culture environment more representative of that in vivo than other culture
systems. They are useful for performing mechanistic studies of respiratory
epithelial cells as drug permeation barriers and can be used to study the
interactions between hosts and respiratory pathogens. However, there have been
few studies concerning Ali cultures of primary swine tracheal epithelial cells
(STECs) and an immortalized STEC line, and the differences between these two
systems remain poorly defined. RESULTS: In this study, we established Ali culture
systems for primary STECs and for immortalized STEC line, and we systematically
compared the differentiation capacities and immunological functions of these
systems for the first time. Under Ali culture conditions, immortalized STEC line
and primary STECs could survive for at least forty days, formed tight junctions
and differentiated into stratified cells. They both possessed complete abilities
to produce mucin and inflammatory cytokines and develop cilia. However, in
contrast to primary STECs, which had a heterogeneous morphology, Ali-cultured
immortalized STEC line appeared to be a homogenous population. The formation of
tight junctions in Ali-cultured primary STECs was superior to that in
immortalized STEC line. In addition, cilia in Ali-cultured immortalized STEC line
were more pronounced, but their duration of expression was shorter than in
primary STECs. CONCLUSIONS: Ali-cultured primary STECs and immortalized STEC line
systems possessing complete abilities to undergo ciliary differentiation and
inflammatory cytokine production were established for the first time in this
study, and several differences in morphology and the formation of tight junctions
and cilia were observed between these two systems. These two systems will be
important tools for drug screening studies, as well as for detailed analyses of
the interactions between hosts and respiratory pathogens.
PMID- 29954318
TI - FamPlex: a resource for entity recognition and relationship resolution of human
protein families and complexes in biomedical text mining.
AB - BACKGROUND: For automated reading of scientific publications to extract useful
information about molecular mechanisms it is critical that genes, proteins and
other entities be correctly associated with uniform identifiers, a process known
as named entity linking or "grounding." Correct grounding is essential for
resolving relationships among mined information, curated interaction databases,
and biological datasets. The accuracy of this process is largely dependent on the
availability of machine-readable resources associating synonyms and abbreviations
commonly found in biomedical literature with uniform identifiers. RESULTS: In a
task involving automated reading of ~215,000 articles using the REACH event
extraction software we found that grounding was disproportionately inaccurate for
multi-protein families (e.g., "AKT") and complexes with multiple subunits
(e.g."NF- kappaB"). To address this problem we constructed FamPlex, a manually
curated resource defining protein families and complexes as they are commonly
encountered in biomedical text. In FamPlex the gene-level constituents of
families and complexes are defined in a flexible format allowing for multi-level,
hierarchical membership. To create FamPlex, text strings corresponding to
entities were identified empirically from literature and linked manually to
uniform identifiers; these identifiers were also mapped to equivalent entries in
multiple related databases. FamPlex also includes curated prefix and suffix
patterns that improve named entity recognition and event extraction. Evaluation
of REACH extractions on a test corpus of ~54,000 articles showed that FamPlex
significantly increased grounding accuracy for families and complexes (from 15 to
71%). The hierarchical organization of entities in FamPlex also made it possible
to integrate otherwise unconnected mechanistic information across families,
subfamilies, and individual proteins. Applications of FamPlex to the TRIPS/DRUM
reading system and the Biocreative VI Bioentity Normalization Task dataset
demonstrated the utility of FamPlex in other settings. CONCLUSION: FamPlex is an
effective resource for improving named entity recognition, grounding, and
relationship resolution in automated reading of biomedical text. The content in
FamPlex is available in both tabular and Open Biomedical Ontology formats at
https://github.com/sorgerlab/famplex under the Creative Commons CC0 license and
has been integrated into the TRIPS/DRUM and REACH reading systems.
PMID- 29954319
TI - Characterisation of the cellular and proteomic response of Galleria mellonella
larvae to the development of invasive aspergillosis.
AB - BACKGROUND: Galleria mellonella larvae were infected with conidia of Aspergillus
fumigatus and the cellular and humoral immune responses of larvae to the pathogen
were characterized as invasive aspergillosis developed. RESULTS: At 2 h post
infection there was an increase in hemocyte density to 7.43 +/- 0.50 * 106/ml
from 0.98 +/- 0.08 * 106/ml at 0 h. Hemocytes from larvae immune primed for 6 h
with heat killed A. fumigatus conidia displayed superior anti-fungal activity.
Examination of the spread of the fungus by Cryo-imaging and fluorescent
microscopy revealed dissemination of the fungus through the larvae by 6 h and the
formation of distinct nodules in tissue. By 24 h a range of nodules were visible
at the site of infection and at sites distant from that indicating invasion of
tissue. Proteomic analysis of larvae infected with viable conidia for 6 h
demonstrated an increase in the abundance of gustatory receptor candidate 25 (37
fold), gloverin-like protein (14 fold), cecropin-A (11 fold). At 24 h post
infection gustatory receptor candidate 25 (126 fold), moricin-like peptide D (33
fold) and muscle protein 20-like protein (12 fold) were increased in abundance.
Proteins decreased in abundance included fibrohexamerin (13 fold) and dimeric
dihydrodiol dehydrogenase (8 fold). CONCLUSION: The results presented here
indicate that G. mellonella larvae may be a convenient model for studying the
stages in the development of invasive aspergillosis and may offer an insight into
this process in mammals.
PMID- 29954320
TI - Evaluating the effect of magnesium supplementation and cardiac arrhythmias after
acute coronary syndrome: a systematic review and meta-analysis.
AB - BACKGROUND: Atrial and ventricular cardiac arrhythmias are one of the most common
early complications after cardiac surgery and these serve as a major cause of
mortality and morbidity after cardiac revascularization. We want to evaluate the
effect of magnesium sulfate administration on the incidence of cardiac
arrhythmias after cardiac revascularization by doing this systematic review and
meta-analysis. METHODS: The search performed in several databases (SID, Magiran,
IranDoc, IranMedex, MedLib, PubMed, EmBase, Web of Science, Scopus, the Cochrane
Library and Google Scholar) for published Randomized controlled trials before
December 2017 that have reported the association between Magnesium consumption
and the incidence of cardiac arrhythmias. This relationship measured using odds
ratios (ORs) with a confidence interval of 95% (CIs). Funnel plots and Egger test
used to examine publication bias. STATA (version 11.1) used for all analyses.
RESULTS: Twenty-two studies selected as eligible for this research and included
in the final analysis. The total rate of ventricular arrhythmia was lower in the
group receiving magnesium sulfate than placebo (11.88% versus 24.24%). The same
trend obtained for the total incidence of supraventricular arrhythmia (10.36% in
the magnesium versus 23.91% in the placebo group). In general the present meta
analysis showed that magnesium could decrease ventricular and supraventricular
arrhythmias compared with placebo (OR = 0.32, 95% CI 0.16-0.49; p < 0.001 and OR
= 0.42, 95% CI 0.22-0.65; p < 0.001, respectively). Subgroup analysis showed that
the effect of magnesium on the incidence of cardiac arrhythmias was not affected
by clinical settings and dosage of magnesium. Meta-regression analysis also
showed that there was no significant association between the reduction of
ventricular arrhythmias and sample size. CONCLUSION: The results of this meta
analysis study suggest that magnesium sulfate can be used safely and effectively
and is a cost-effective way in the prevention of many of ventricular and
supraventricular arrhythmias.
PMID- 29954321
TI - Bacille Calmette-Guerin (BCG) spondylitis with adjacent mycotic aortic aneurysm
after intravesical BCG therapy: a case report and literature review.
AB - BACKGROUND: Although intravesical bacille Calmette-Guerin (BCG) therapy is
accepted as an effective treatment for bladder cancer, serious complications may
occur in rare cases. To date, only 4 cases have been reported in which the
patient developed a combination of mycotic aortic aneurysm and BCG spondylitis.
Accurate diagnosis of BCG spondylitis is important because it is an iatrogenic
disease, and its treatment is different from usual tuberculous spondylitis.
However, distinguishing BCG spondylitis from usual tuberculous spondylitis is
very difficult and takes a long time. In this study, we were able to suspect BCG
spondylitis at an early stage from the result of the interferon-gamma release
assay (IGRA). CASE PRESENTATION: We encountered a case of BCG spondylitis with
adjacent mycotic aortic aneurysm after intravesical BCG therapy in a 76-year-old
man. We performed a 2-stage operation to obtain spine stabilization and replace
the aneurysm with a synthetic graft. We started multidrug therapy with
antituberculosis medication, excluding pyrazinamide, because the patient's
history of BCG therapy, negative IGRA, and positive of tuberculosis-polymerase
chain reaction (Tb-PCR) suggested that the pathogenic bacteria of the spondylitis
was BCG. Eventually the bacterial strain was identified as BCG by PCR-based
genomic deletion analysis. CONCLUSIONS: BCG infection should be considered in
patients who have been treated with BCG therapy, even if the treatment was
performed several months to several years previously. In the case of a patient
with a history of BCG therapy, a positive Tb-PCR result and negative IGRA result
probably suggest BCG infections, if the possibility of false-negative IGRA result
can be excluded.
PMID- 29954322
TI - The use of single armed observational data to closing the gap in otherwise
disconnected evidence networks: a network meta-analysis in multiple myeloma.
AB - BACKGROUND: Network meta-analysis (NMA) allows for the estimation of comparative
effectiveness of treatments that have not been studied in head-to-head trials;
however, relative treatment effects for all interventions can only be derived
where available evidence forms a connected network. Head-to-head evidence is
limited in many disease areas, regularly resulting in disconnected evidence
structures where a large number of treatments are available. This is also the
case in the evidence of treatments for relapsed or refractory multiple myeloma.
METHODS: Randomised controlled trials (RCTs) identified in a systematic
literature review form two disconnected evidence networks. Standard Bayesian NMA
models are fitted to obtain estimates of relative effects within each network.
Observational evidence was identified to fill the evidence gap. Single armed
trials are matched to act as each other's control group based on a distance
metric derived from covariate information. Uncertainty resulting from including
this evidence is incorporated by analysing the space of possible matches.
RESULTS: Twenty five randomised controlled trials form two disconnected evidence
networks; 12 single armed observational studies are considered for bridging
between the networks. Five matches are selected to bridge between the networks.
While significant variation in the ranking is observed, daratumumab in
combination with dexamethasone and either lenalidomide or bortezomib, as well as
triple therapy of carfilzomib, ixazomib and elozumatab, in combination with
lenalidomide and dexamethasone, show the highest effects on progression free
survival, on average. CONCLUSIONS: The analysis shows how observational data can
be used to fill gaps in the existing networks of RCT evidence; allowing for the
indirect comparison of a large number of treatments, which could not be compared
otherwise. Additional uncertainty is accounted for by scenario analyses reducing
the risk of over confidence in interpretation of results.
PMID- 29954323
TI - Numerical analysis of the impact of flow rate, heart rate, vessel geometry, and
degree of stenosis on coronary hemodynamic indices.
AB - BACKGROUND: The stenosis of the coronary arteries is usually caused by
atherosclerosis. Hemodynamic significance of patient-specific coronary stenoses
and the risk of its progression may be assessed by comparing the hemodynamic
effects induced by flow disorders. The present study shows how stenosis degree
and variable flow conditions in coronary artery affect the oscillating shear
index, residence time index, pressure drop coefficient and fractional flow
reserve. We assume that changes in the hemodynamic indices in relation to
variable flow conditions and geometries evaluated using the computational fluid
dynamics may be an additional factor for a non-invasive assessment of the
coronary stenosis detected on multi-slice computed tomography. METHODS: The local
parametrised models of basic shapes of the vessels, such as straight section,
bend, and bifurcation as well as the global-patient-specific models of left
coronary artery were used for numerical simulation of flow in virtually
reconstructed stenotic vessels. Calculations were carried out for vessels both
without stenosis, and vessels of 10 to 95% stenosis. The flow rate varied within
the range of 20 to 1000 ml/min, and heart rate frequency within the range of 30
to 210 cycles/min. The computational fluid dynamics based on the finite elements
method verified by the experimental measurements of the velocity profiles was
used to analyse blood flow in the coronary arteries. RESULTS: The results confirm
our preliminary assumptions. There is significant variation in the coronary
hemodynamic indices value caused by disturbed flow through stenosis in relation
to variable flow conditions and geometry of vessels. CONCLUSION: Variations of
selected hemodynamic indexes induced by change of flow rate, heart rate and
vessel geometry, obtained during a non-invasive study, may assist in evaluating
the risk of stenosis progression and in carrying out the assessment of the
hemodynamic significance of coronary stenosis. However, for a more accurate
assessment of the variability of indices and coronary stenosis severity both
local (near the narrowing) and global (in side branches) studies should be used.
PMID- 29954324
TI - Pneumatosis cystoides intestinalis: six case reports and a review of the
literature.
AB - BACKGROUND: Pneumatosis cystoides intestinalis (PCI) is characterized by gas
filled cysts in the intestinal submucosa and subserosa. There are few reports of
PCI occurring in duodenum and rectum. Here we demonstrated four different
endoscopic manifestations of PCI and three cases with intestinal stricture all
were successfully managed by medical conservative treatment. CASE PRESENTATION:
There are 6 cases of PCI with varied causes encountered, in which the etiology,
endoscopic features, treatment methods and prognosis of patients were studied.
One case was idiopathic, while the other one case was caused by exposing to
trichloroethylene (TCE), and the remaining four cases were secondary to diabetes,
emphysema, therioma and diseases of immune system. Of the six patients, all
complained of abdominal distention or diarrhea, three (50%) reported muco-bloody
stools, two (33.3%) complained of abdominal pain. In four other patients, PCI
occurred in the colon, especially the sigmoid colon, while in the other two
patients, it occurred in duodenum and rectum. Endoscopic findings were divided
into bubble-like pattern, grape or beaded circular forms, linear or cobblestone
gas formation and irregular forms. After combination of medicine and endoscopic
treatment, the symptoms of five patients were relieved, while one patient died of
malignant tumors. CONCLUSION: PCI endoscopic manifestations were varied, and
radiology combined with endoscopy can avoid misdiagnosis. The primary bubble-like
pattern can be cured by endoscopic resection, while removal of etiology combined
with drug therapy can resolve majority of secondary cases, thereby avoiding the
adverse risks of surgery.
PMID- 29954325
TI - Identification of differentially expressed genes and pathways in mice exposed to
mixed field neutron/photon radiation.
AB - BACKGROUND: Radiation exposure due to the detonation of an improvised nuclear
device remains a major security concern. Radiation from such a device involves a
combination of photons and neutrons. Although photons will make the greater
contribution to the total dose, neutrons will certainly have an impact on the
severity of the exposure as they have high relative biological effectiveness.
RESULTS: We investigated the gene expression signatures in the blood of mice
exposed to 3 Gy x-rays, 0.75 Gy of neutrons, or to mixed field photon/neutron
with the neutron fraction contributing 5, 15%, or 25% of a total 3 Gy radiation
dose. Gene ontology and pathway analysis revealed that genes involved in protein
ubiquitination pathways were significantly overrepresented in all radiation doses
and qualities. On the other hand, eukaryotic initiation factor 2 (EIF2) signaling
pathway was identified as one of the top 10 ranked canonical pathways in neutron,
but not pure x-ray, exposures. In addition, the related mTOR and regulation of
EIF4/p70S6K pathways were also significantly underrepresented in the exposures
with a neutron component, but not in x-ray radiation. The majority of the changed
genes in these pathways belonged to the ribosome biogenesis and translation
machinery and included several translation initiation factors (e.g. Eif2ak4,
Eif3f), as well as 40S and 60S ribosomal subunits (e.g. Rsp19, Rpl19, Rpl27).
Many of the differentially downregulated ribosomal genes (e.g. RPS19, RPS28) have
been causally associated with human bone marrow failure syndromes and hematologic
malignancies. We also observed downregulation of transfer RNA processes, in the
neutron-only exposure (p < 0.005). Ingenuity Pathway Analysis (p < 0.05) of
differentially expressed genes predicted significantly suppressed activity of the
upstream regulators c-Myc and Mycn, transcription factors known to control
ribosome biogenesis. CONCLUSIONS: We describe the gene expression profile of
mouse blood following exposure to mixed field neutron/photon irradiation. We have
discovered that pathways related to protein translation are significantly
underrepresented in the exposures containing a neutron component. Our results
highlight the significance of neutron exposures that even the smallest percentage
can have profound biological effects that will affect medical management and
treatment decisions in case of a radiological emergency.
PMID- 29954326
TI - The values of applying classification and counts of white blood cells to the
prognostic evaluation of resectable gastric cancers.
AB - BACKGROUND: The classifications and counts of white blood cells (WBCs) have been
proved to be able to be used as prognostic markers in cancer cases. The present
study investigated the potential values of the classifications and counts of WBC,
including lymphocyte (LY), monocyte (MO), neutrophil (NE), eosinophil (EO), and
basophil (BA) in the prognosis of resectable gastric cancers (GCs). METHODS: This
retrospective study recruited 104 resectable GC cases which were pathologically
confirmed. The patients were divided into two groups according to the median pre
treatment values. To evaluate the changes in WBC counts and classification after
treatment, we introduced the concept of post/pre-treatment ratios (<= 1 indicated
count was not increased after therapy, while > 1 suggested increased count).
RESULTS: Pre-treatment NE and total WBC counts were negatively correlated with
overall survival (OS). Surgery significantly decreased the level of NE count, but
increased the level of EO, whereas had no effect on the levels of LY, MO, BAor
total WBC. Adjuvant chemotherapy significantly decreased the level of BA. Whole
course of treatment (surgery combined with adjuvant chemotherapy) had no
significant effect on the counts of LY, MO, NE, EO, BA or total WBC. Post/pre
treatment ratios of LY, MO NE, EO, BA and total WBC levels had no effects on OS.
Univariate analysis indicated that AJCC stage (III) and higher level of pre
treatment total WBC count were prognostic factors affecting OS. Multivariate Cox
regression analysis revealed that AJCC stage (III) and higher level of pre
treatment total WBC count were independent prognostic factors. CONCLUSIONS: Pre
treatment NE count and pre-treatment total WBC count may be potential prognostic
factors for the prognostic evaluation of GCs.
PMID- 29954327
TI - Identification and differential regulation of microRNAs during thyroid hormone
dependent metamorphosis in Microhyla fissipes.
AB - BACKGROUND: Anuran metamorphosis, which is obligatorily initiated and sustained
by thyroid hormone (TH), is a dramatic example of extensive morphological,
biochemical and cellular changes occurring during post-embryonic development.
Thus, it provides an ideal model to understand the actions of the hormone and
molecular mechanisms underlying these developmental and apoptotic processes. In
addition to transcriptional factors, microRNAs (miRNAs) play key roles in diverse
biological processes via post-transcriptional repression of mRNAs. However, the
possible role of miRNAs in anuran metamorphosis is not well understood. Screening
and identification of TH-responding miRNAs are required to reveal the integrated
regulatory mechanisms of TH during metamorphosis. Given the specific role of TRs
during M. fissipes metamorphosis and the characteristics of M. fissipes as an
ideal model, Illumina sequencing technology was employed to get a full scope of
miRNA in M. fissipes metamorphosis treated by T3. RESULTS: Morphological and
histological analysis revealed that 24 h T3 treatment M. fissipes tadpoles
resembled that at the climax of natural metamorphosis. Thus, small RNA libraries
were constructed from control and 24 h T3 treatment groups. A total of 164
conserved miRNAs and 36 predicted novel miRNAs were characterized. Furthermore,
5' first and ninth nucleotides of miRNAs were significantly enriched in U in our
study. In all, 21 miRNAs were differentially expressed between the T3 and control
groups (p < 0.01). A total of 10,206 unigenes were identified as target genes of
these differentially expressed miRNAs. KEGG pathway analysis indicated that the
most overrepresented miRNA target genes were enriched in the "PI3k-Akt signaling
pathway". In addition, a network associated with the TH signaling pathway
provides an opportunity to further understand the complex biological processes
that occur in metamorphosis. CONCLUSIONS: We identified a large number of miRNAs
during M. fissipes metamorphosis, and 21 of them were differentially expressed in
the two groups that represented two different metamorphic stages. These miRNAs
may play important roles during metamorphosis. The study gives us clues for
further studies of the mechanisms of anuran metamorphosis and provides a model to
study the mechanism of TH-affected biological processes in humans.
PMID- 29954328
TI - Cytomegalovirus infection and outcome in immunocompetent patients in the
intensive care unit: a systematic review and meta-analysis.
AB - BACKGROUND: Cytomegalovirus (CMV) infection is common in immunocompetent patients
in intensive care units (ICUs). However, whether CMV infection or CMV
reactivation contributes to mortality of immunocompetent patients remains
unclear. METHODS: A literature search was conducted for relevant studies
published before May 30, 2016. Studies reporting on CMV infection in
immunocompetent patients in ICUs and containing 2 * 2 tables on CMV results and
all-cause mortality were included. RESULTS: Eighteen studies involving 2398
immunocompetent patients admitted to ICUs were included in the meta-analysis. The
overall rate of CMV infection was 27% (95%CI 22-34%, I2 = 89%, n = 2398) and the
CMV reactivation was 31% (95%CI 24-39%, I2 = 74%, n = 666). The odds ratio (OR)
for all-cause mortality among patients with CMV infection, compared with those
without infection, was 2.16 (95%CI 1.70-2.74, I2 = 10%, n = 2239). Moreover, upon
exclusion of studies in which antiviral treatment was possibly or definitely
provided to some patients, the association of mortality rate with CMV infection
was also statistically significant (OR: 1.69, 95%CI 1.01-2.83, I2 = 37%, n =
912,). For CMV seropositive patients, the OR for mortality in patients with CMV
reactivation as compared with patients without CMV reactivation was 1.72 (95%CI
1.04-2.85, I2 = 29%, n = 664). Patients with CMV infection required significantly
longer mechanical ventilation (mean difference (MD): 9 days (95% CI 5-14, I2 =
81%, n = 875)) and longer duration of ICU stay (MD: 12 days (95% CI 7-17, I2 =
70%, n = 949)) than patients without CMV infection. When analysis was limited to
detection in blood, CMV infection without antiviral drug treatment or
reactivation was not significantly associated with higher mortality (OR: 1.69,
95%CI 0.81-3.54, I2 = 52%, n = 722; OR: 1.49, I2 = 63%, n = 469). CONCLUSION:
Critically ill patients without immunosuppression admitted to ICUs show a high
rate of CMV infection. CMV infection during the natural unaltered course or
reactivation in critically ill patients is associated with increased mortality,
but have no effect on mortality when CMV in blood. More studies are needed to
clarify the impact of CMV infection on clinical outcomes in those patients.
PMID- 29954330
TI - Transferring knowledge of bacterial protein interaction networks to predict
pathogen targeted human genes and immune signaling pathways: a case study on M.
tuberculosis.
AB - BACKGROUND: Bacterial invasive infection and host immune response is fundamental
to the understanding of pathogen pathogenesis and the discovery of effective
therapeutic drugs. However, there are very few experimental studies on the
signaling cross-talks between bacteria and human host to date. METHODS: In this
work, taking M. tuberculosis H37Rv (MTB) that is co-evolving with its human host
as an example, we propose a general computational framework that exploits the
known bacterial pathogen protein interaction networks in STRING database to
predict pathogen-host protein interactions and their signaling cross-talks. In
this framework, significant interlogs are derived from the known pathogen protein
interaction networks to train a predictive l2-regularized logistic regression
model. RESULTS: The computational results show that the proposed method achieves
excellent performance of cross validation as well as low predicted positive rates
on the less significant interlogs and non-interlogs, indicating a low risk of
false discovery. We further conduct gene ontology (GO) and pathway enrichment
analyses of the predicted pathogen-host protein interaction networks, which
potentially provides insights into the machinery that M. tuberculosis H37Rv
targets human genes and signaling pathways. In addition, we analyse the pathogen
host protein interactions related to drug resistance, inhibition of which
potentially provides an alternative solution to M. tuberculosis H37Rv drug
resistance. CONCLUSIONS: The proposed machine learning framework has been
verified effective for predicting bacteria-host protein interactions via known
bacterial protein interaction networks. For a vast majority of bacterial
pathogens that lacks experimental studies of bacteria-host protein interactions,
this framework is supposed to achieve a general-purpose applicability. The
predicted protein interaction networks between M. tuberculosis H37Rv and Homo
sapiens, provided in the Additional files, promise to gain applications in the
two fields: (1) providing an alternative solution to drug resistance; (2)
revealing the patterns that M. tuberculosis H37Rv genes target human immune
signaling pathways.
PMID- 29954329
TI - Single SNP- and pathway-based genome-wide association studies for beak deformity
in chickens using high-density 600K SNP arrays.
AB - BACKGROUND: Beak deformity, typically expressed as the crossing of upper and
lower mandibles, is found in several indigenous chicken breeds, including the
Beijing-You chickens studied here. Beak deformity severely impairs the birds'
growth and welfare. Although previous studies shed some light on the genetic
regulation of this complex trait, the genetic basis of this malformation remains
incompletely understood. RESULTS: In this study, single SNP- and pathway-based
genome-wide association studies (GWASs) were performed using ROADTRIPS and SNP
ratio test (SRT), respectively. A total of 48 birds with deformed beaks (case)
and 48 normal birds (control) were genotyped using Affymetrix 600 K HD genotyping
arrays. As a result, 95 individuals and 429,539 SNPs were obtained after quality
control. The P-value was corrected by a Bonferroni adjustment based on linkage
disequilibrium pruning. The single SNP-based association study identified one
associated SNP with 5% genome-wide significance and seven suggestively associated
SNPs. Four high-confidence genes, LOC421892, TDRD3, RET, and STMN1, were
identified as the most promising candidate genes underlying this complex trait in
view of their positions, functions, and overlaps with previous studies. The
pathway-based association study highlighted the association of six pathways with
beak deformity, including the calcium signaling pathway. CONCLUSIONS: Potentially
useful candidate genes and pathways for beak deformity were identified, which
should be the subject of further functional characterization.
PMID- 29954332
TI - Comparison of AIMS65, Glasgow-Blatchford and Rockall scoring approaches in
predicting the risk of in-hospital death among emergency hospitalized patients
with upper gastrointestinal bleeding: a retrospective observational study in
Nanjing, China.
AB - BACKGROUND: This study aims to compare the performance of AIMS65, Glasgow
Blatchford (GBS) and Rockall scores (RS) in predicting the death risk among
emergency-hospitalized patients with upper gastrointestinal bleeding (UGIB) in
regional China. METHODS: A retrospective study was implemented between January
2014 and December 2015. Eligible participants were those who were hospitalized
with UGIB. The outcome variable was in-hospital death, while explanatory
variables were AIMS65, GBS and RS scores. Odds ratios (OR) and 95% confidence
interval (CI) were estimated to assess the association of AIMS65, GBS and RS with
death risk using multivariate logistic regression models. The areas under the
receiver operating characteristics curve (AUC) of three scoring systems were
computed to compare their predictive power. RESULTS: Among 799 UGIB participants,
674 were non-variceal bleeding (NVUGIB) and 125 variceal bleeding (VUGIB)
patients. AIMS65 (OR = 14.72, 95% CI = 6.48, 33.43) and RS (OR = 1.60, 95% CI =
1.20, 2.13) were positively associated with the risk of in-hospital death.
Moreover, AIMS65 (AUC = 0.91, 95% CI = 0.84, 0.98) performed the best in
predicting in-hospital death, followed by RS (AUC = 0.79, 95% CI = 0.72, 0.86)
and GBS (AUC = 0.71, 95% CI = 0.59, 0.83) among overall UGIB participants. AIMS65
was also the best indicator to predict in-hospital death among either NVUGIB
participants (AUC = 0.89, 95% CI = 0.80, 0.98) or VUGIB participants (AUC = 0.94,
95% CI = 0.89, 1.00). CONCLUSIONS: AIMS65, GBS and RS scoring approaches were all
acceptable for predicting in-hospital death among UGIB patients irrespective of
the subtype of UGIB in China. The AIMS65 might be the most powerful predictor.
PMID- 29954331
TI - Once-weekly hemodialysis combined with low-protein and low-salt dietary treatment
as a favorable therapeutic modality for selected patients with end-stage renal
failure: a prospective observational study in Japanese patients.
AB - BACKGROUND: For patients with end-stage renal failure (ESFR), thrice-weekly
hemodialysis is a standard care. Once-weekly hemodialysis combined with low
protein and low-salt dietary treatment (OWHD-DT) have been rarely studied.
Therefore, here, we describe our experience on OWHD-DT, and assess its long-term
effectiveness. METHODS: We instituted OWHD-DT therapy in 112 highly motivated
patients with creatinine clearance below 5.0 mL/min. They received once-weekly
hemodialysis on a diet of 0.6 g/kg/day of protein adjusted for sufficient energy
intake, and less than 6 g/day of salt intake. Serial changes in their clinical,
biochemical and nutritional parameters were prospectively observed, and the
weekly time spent for hospital visits as well as their monthly medical expenses
were compared with 30 age, sex- and disease-matched thrice-weekly hemodialysis
patients. RESULTS: The duration of successfully continued OWHD-DT therapy was
more than 4 years in 11.6% of patients, 3 years in 16.1%, 2 years in 24.1% and 1
year in 51.8%. Time required per week for hospital attendance was 66.7% shorter
and monthly medical expenses were 50.5% lower in the OWHD-DT group than in the
thrice-weekly hemodialysis group (both p < 0.001). Patient survival rates in the
OWHD-DT group were better than those in the Japan Registry (p < 0.001). Serum
urea nitrogen significantly decreased; hemoglobin significantly increased; and
albumin and body mass index were not significantly different from baseline
values. In the OWHD-DT patients, serum albumin at 1 and 2 years after initiation
of therapy was significantly higher compared with prevalent thrice-weekly
hemodialysis patients. Furthermore, residual urine output was significantly
higher in the OWHD-DT patients than in those receiving thrice-weekly hemodialysis
(p < 0.05). Interdialytic weight gain over the course of the entire week between
treatments in patients on OWHD-DT were 0.9 +/- 1.0, 2.0 +/- 1.3, 1.9 +/- 1.2, 1.9
+/- 1.5 and 1.8 +/- 1.0 kg at 1, 6, 12, 18 and 24 months, respectively, though
the weekly weight gain for thrice-weekly hemodialysis group (summed over all 3
treatments) was 8.6 +/- 0.63 kg, p < 0.001. CONCLUSIONS: OWHD-DT may be a
favorable therapeutic modality for selected highly motivated patients with ESRF.
However, this treatment cannot be seen as a general maintenance strategy. TRIAL
REGISTRATION: UMIN000027555 , May 30, 2017 (retrospectively registered).
PMID- 29954334
TI - Adhesive intestinal obstruction increases the risk of intestinal perforation in
peritoneal dialysis patients: a case report.
AB - BACKGROUND: Peritonitis secondary to bowel perforation is a rare and potentially
fatal complication in peritoneal dialysis (PD) patients. However, the early
diagnosis of bowel perforation is difficult in PD patients because the initial
symptoms and signs of bowel perforation are similar to those of PD-associated
peritonitis. Furthermore, the risk of bowel perforation in PD patients is
unclear. Here, we present a case of intestinal perforation located at the site of
adhesive intestinal obstruction in a PD patient. CASE PRESENTATION: A 73-year-old
man on PD presented with progressive worsening of abdominal pain and cloudy
peritoneal fluid. The peritoneal fluid cell count was increased to 980/ml and
peritoneal dialysis-associated peritonitis was diagnosed. Computed tomography
showed local adhesions causing agglomeration of the dilated intestine. He
initially responded to antibiotic treatment; however, his abdominal pain was
rapidly worsened after resumption of oral intake. On hospital day 23, computed
tomography showed loss of contents from the dilated intestine and discharge of
fecal material from the PD tube was noted. Thus, small bowel perforation was
diagnosed, and he underwent ileocecal resection with colostomy creation. As
indicators of EPS was not evident, PD catheter was removed. Since then, he has
been on maintenance of hemodialysis since then. CONCLUSION: The findings of the
present case suggest that adhesive intestinal obstruction in PD patients can
increase the risk of intestinal perforation. Careful monitoring for the early
detection of intestinal perforation is required in such cases.
PMID- 29954333
TI - The effectiveness of shared decision-making followed by positive reinforcement on
physical disability in the long-term follow-up of patients with nonspecific low
back pain in primary care: a clustered randomised controlled trial.
AB - BACKGROUND: Although the recovery of patients suffering from low back pain is
highly context dependent, patient preferences about treatment options are seldom
incorporated into the therapeutic plan. Shared decision-making (SDM) offers a
tool to overcome this deficiency. The reinforcement by the general practitioner
(GP) of a 'shared' chosen therapy might increase patients' expectations of
favourable outcomes and thus contribute to recovery. METHODS: In the Netherlands,
a clustered randomised controlled trial was performed to assess the effectiveness
of shared decision-making followed by positive reinforcement of the chosen
therapy (SDM&PR) on patient-related clinical outcomes. Overall, 68 GPs included
226 patients visiting their GP for a new episode of non-chronic low back pain.
GPs in the intervention group were trained in implementing SDM&PR using a
structured training programme with a focus on patient preferences in reaching
treatment decisions. GPs in the control group provided care as usual. The primary
outcome was the change in physical disability measured with the Roland-Morris
disability questionnaire (RMD) during the six-month follow-up after the first
consultation. Physical disability (RMD), pain, adequate relief, absenteeism and
healthcare consumption at 2, 6, 12 and 26 weeks were secondary outcomes. A
multivariate analysis with a mixed model was used to estimate the differences in
outcomes. RESULTS: Of the patients in the intervention and the control groups, 66
and 62%, respectively, completed the follow-up. Most patients (77%) recovered to
no functional restrictions due to back pain within 26 weeks. No significant
differences in the mean scores for any outcome were observed between intervention
patients and controls during the follow-up, and in multivariate analysis, there
was no significant difference in the main outcome during the six-month follow-up.
Patients in the intervention group reported more involvement in decision-making.
CONCLUSION: This study did not detect any improvement in clinical outcome or in
health care consumption of patients with non-chronic low back pain after the
training of GPs in SDM&PR. The implementation of SDM merely introduces task
oriented communication. The training of the GPs may have been more effective if
it had focused more on patient-oriented communication techniques and on stressing
the expectation of favourable outcomes. TRIAL REGISTRATION: The Netherlands
National Trial Register (NTR) number: NTR1960. The trial was registered in the
NTR on August 20, 2009.
PMID- 29954335
TI - Quorum sensing in thermophiles: prevalence of autoinducer-2 system.
AB - BACKGROUND: Quorum sensing is a mechanism of cell to cell communication that
requires the production and detection of signaling molecules called autoinducers.
Although mesophilic bacteria is known to utilize this for synchronization of
physiological processes such as bioluminescence, virulence, biofilm formation,
motility and cell competency through signaling molecules (acyl homoserine
lactones, AI-1; oligopeptides, peptide based system and furanosyl borate diester,
AI-2), the phenomenon of quorum sensing in thermophiles is largely unknown.
RESULTS: In this study, proteomes of 106 thermophilic eubacteria and 21
thermophilic archaea have been investigated for the above three major quorum
sensing systems to find the existence of quorum sensing in these thermophiles as
there are evidences for the formation of biofilms in hot environments. Our
investigation demonstrated that AI-1 system is absent in thermophiles. Further,
complete peptide based two component systems for quorum sensing was also not
found in any thermophile however the traces for the presence of response
regulators for peptide based system were found in some of them. BLASTp search
using LuxS (AI-2 synthase) protein sequence of Escherichia coli str. K-12 substr.
MG1655 and autoinducer-2 receptors (LuxP of Vibrio harveyi, LsrB of E. coli str.
K-12 substr. MG1655 and RbsB of Aggregatibacter actinomycetemcomitans) as queries
revealed that 17 thermophilic bacteria from phyla Deinococcus- Thermus and
Firmicutes possess complete AI-2 system (LuxS and LsrB and/or RbsB). Out of 106
thermophilic eubacteria 18 from phyla Deinococcus- Thermus, Proteobacteria and
Firmicutes have only LuxS that might function as AI-2 synthesizing protein
whereas, 16 are having only LsrB and/or RbsB which may function as AI-2 receptor
in biofilms. CONCLUSIONS: We anticipate that thermophilic bacteria may use
elements of LsrB and RbsB operon for AI-2 signal transduction and they may use
quorum sensing for purposes like biofilm formation. Nevertheless, thermophiles in
which no known quorum sensing system was found may use some unknown mechanisms as
the mode of communication. Further information regarding quorum sensing will be
explored to develop strategies to disrupt the biofilms of thermophiles.
PMID- 29954337
TI - Development and validation of a heart failure with preserved ejection fraction
cohort using electronic medical records.
AB - BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) comprises
nearly half of prevalent HF, yet is challenging to curate in a large database of
electronic medical records (EMR) since it requires both accurate HF diagnosis and
left ventricular ejection fraction (EF) values to be consistently >=50%. METHODS:
We used the national Veterans Affairs EMR to curate a cohort of HFpEF patients
from 2002 to 2014. EF values were extracted from clinical documents utilizing
natural language processing and an iterative approach was used to refine the
algorithm for verification of clinical HFpEF. The final algorithm utilized the
following inclusion criteria: any International Classification of Diseases-9 (ICD
9) code of HF (428.xx); all recorded EF >=50%; and either B-type natriuretic
peptide (BNP) or aminoterminal pro-BNP (NT-proBNP) values recorded OR diuretic
use within one month of diagnosis of HF. Validation of the algorithm was
performed by 3 independent reviewers doing manual chart review of 100 HFpEF cases
and 100 controls. RESULTS: We established a HFpEF cohort of 80,248 patients (out
of a total 1,155,376 patients with the ICD-9 diagnosis of HF). Mean age was 72
years; 96% were males and 12% were African-Americans. Validation analysis of the
HFpEF algorithm had a sensitivity of 88%, specificity of 96%, positive predictive
value of 96%, and a negative predictive value of 87% to identify HFpEF cases.
CONCLUSION: We developed a sensitive, highly specific algorithm for detecting
HFpEF in a large national database. This approach may be applicable to other
large EMR databases to identify HFpEF patients.
PMID- 29954336
TI - Histological findings to five years after early conversion of kidney transplant
patients from cyclosporine to everolimus: an analysis from the randomized ZEUS
study.
AB - BACKGROUND: Conversion from calcineurin inhibitor (CNI) therapy to everolimus
within 6 months after kidney transplantation improves long-term graft function
but can increase the risk of mild biopsy-proven acute cellular rejection (BPAR).
We performed a post-hoc analysis of histological data from a randomized trial in
order to further analyze histologic information obtained from indication and
protocol biopsies up to 5 years after transplantation. METHODS: Biopsy samples
obtained up to 5 years post-transplant were analyzed from the randomized ZEUS
study, in which kidney transplant patients were randomized at month 4.5 to switch
to everolimus (n = 154) or remain on cyclosporine (CsA)-based immunosuppression
(n = 146). All patients received mycophenolate and steroids. RESULTS: At least
one investigator-initiated biopsy was undertaken in 53 patients in each group
between randomization and year 5, with a mean (SD) of 2.6 (1.7) and 2.2 (1.4)
biopsies per patient in the everolimus and CsA groups, respectively. In the
everolimus and CsA groups, investigator-initiated biopsies showed (i) BPAR in
12.3 and 7.5% (p = 0.182) of patients, respectively, with episodes graded mild in
22/24 and 18/20 cases (ii) CsA toxicity lesions in 4.5 and 10.3% of patients (p =
0.076) (iii) antibody-mediated rejection in 0.6 and 2.7% of patients (p = 0.204),
respectively. CONCLUSIONS: This analysis of histological findings in the ZEUS
study to 5 years after kidney transplantation shows no increase in antibody
mediated rejection under everolimus-based therapy with a lower rate of CNI
related toxicity compared to a conventional CsA-based regimen, and confirms the
preponderance of mild BPAR seen in the main study after the early switch to CsA
free everolimus therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00154310 .
Date of registration: September 12, 2005.
PMID- 29954338
TI - Genome-wide epigenetic variation among ash trees differing in susceptibility to a
fungal disease.
AB - BACKGROUND: European ash trees (Fraxinus excelsior) are currently threatened by
ash dieback (ADB) caused by the fungus Hymenoscyphus fraxineus but a small
percentage of the population possesses natural low susceptibility. The genome of
a European ash tree has recently been sequenced. Here, we present whole genome
DNA methylation data for two F. excelsior genotypes with high susceptibility to
ADB, and two genotypes with low susceptibility, each clonally replicated. We also
include two genotypes of Manchurian ash (F. mandshurica), an ash species which
has co-evolved with H. fraxineus and also has low susceptibility to ADB. RESULTS:
In F. excelsior, we find an average methylation level of 76.2% in the CG context,
52.0% in the CHG context, and 13.9% in the CHH context; similar levels to those
of tomato. We find higher methylation in transposable elements as opposed to non
mobile elements, and high densities of Non-Differentially Methylation Positions
(N-DMPs) in genes with housekeeping functions. Of genes putatively duplicated in
whole genome duplication (WGD) events, an average of 25.9% are differentially
methylated in at least one cytosine context, potentially indicative of unequal
silencing. Variability in methylation patterns exists among clonal replicates,
and this is only slightly less than the variability found between different
genotypes. Of twenty genes previously found to have expression levels associated
with ADB susceptibility, we find only two of these have differential methylation
between high and low susceptibility F. excelsior trees. In addition, we identify
1683 significant Differentially Methylated Regions (DMRs) (q-value< 0.001)
between the high and low susceptibility genotypes of F. excelsior trees, of which
665 remain significant when F. mandshurica samples are added to the low
susceptibility group. CONCLUSIONS: We find a higher frequency of differentially
methylated WGD-derived gene duplicates in ash than other plant species previously
studied. We also identify a set of genes with differential methylation between
genotypes and species with high versus low susceptibility to ADB. This provides
valuable foundational data for future work on the role that epigenetics may play
in gene dosage compensation and susceptibility to ADB in ash.
PMID- 29954339
TI - Risk factors for complications and mortality of percutaneous endoscopic
gastrostomy insertion.
AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a relatively safe
procedure; however, acute and chronic complications of PEG have been reported. We
aimed to determine risk factors associated with complications and 30-day
mortality after PEG, based on 11 years of experience at a single tertiary
hospital. METHODS: In total, 401 patients who underwent first PEG insertion at
the Asan Medical Center, Seoul, Korea, between January 2005 and December 2015
were eligible. Medical records were retrospectively reviewed to determine
clinical characteristics and outcomes of 139 and 262 patients who underwent pull
type and introducer-type PEG, respectively. RESULTS: The median age of the
overall population was 68 years, and the median body mass index was 19.5 kg/m2.
Acute and chronic complications developed in 96 (23.9%) and 105 (26.2%) patients.
Acute ileus and chronic tube obstruction were significantly more frequent in the
introducer-type PEG group (p = 0.033 and 0.001, respectively). The 30-day
mortality rate was 5.0% (median survival: 10.5 days). Multivariate analysis
revealed that underlying malignancy was a predictor of acute complications; age
>= 70 years and diabetes mellitus were predictors of chronic complications. The
median follow-up was 354 days. Neurologic disease and malignancy were the most
common indications for PEG. Neurologic diseases were classified into two groups:
stroke and the other neurologic disease group (including dementia, Parkinson's
disease, neuromuscular disease, and hypoxic brain damage). Multivariate analysis
showed that 30-day mortality was significantly lower in the other neurologic
disease group and higher in patients with platelet count < 100,000/MUL, and C
reactive protein (CRP) >= 5 mg/dL. CONCLUSIONS: PEG is a relatively safe and
feasible procedure, but it was associated with significantly higher early
mortality rate in patients with platelet count < 100,000/MUL or CPR>=5mg/dL, and
lower early mortality rate in neurologic disease group including dementia,
Parkinson's disase, neuromuscular disease, and hypoxic brain damage. In addition,
acute complications in patients with underlying malignancy, and chronic
complications in patients aged >=70 and those with diabetes mellitus should be
considered during and after PEG.
PMID- 29954340
TI - INvestigation on Routine Follow-up in CONgestive HearT FAilure Patients with
Remotely Monitored Implanted Cardioverter Defibrillators SysTems (InContact).
AB - BACKGROUND: In heart failure (HF) patients with implantable cardioverter
defibrillators (ICD) or cardiac resynchronisation therapy defibrillators (CRT-D),
remote monitoring has been shown to result in at least non-inferior outcomes
relative to in-clinic visits. We aimed to provide further evidence for this
effect, and to assess whether adding telephone follow-ups to remote follow-ups
influenced outcomes. METHODS: InContact was a prospective, randomised,
multicentre study. Subjects receiving quarterly automated follow-up only
(telemetry group) were compared to those receiving personal physician contact.
Personal contact patients were further divided into those receiving automated
follow-up plus a telephone call (remote+phone subgroup) or in-clinic visits only.
RESULTS: Two hundred and ten patients underwent randomisation (telemetry n = 102;
personal contact n = 108 [remote+phone: n = 53; visit: n = 55]). Baseline
characteristics were comparable between groups and subgroups. Over 12 months,
34.8% of patients experienced deterioration of their Packer Clinical Composite
Response, with no significant difference between the telemetry group and personal
care (p > 0.999), remote+phone (p = 0.937) or visit (p = 0.940) patients;
predefined non-inferiority criteria were met. Mortality rates (5.2% overall) were
comparable between groups and subgroups (p = 0.832/p = 0.645), as were HF
hospitalisation rates (11.0% overall; p = 0.605/p = 0.851). The proportion of
patients requiring >=1 unscheduled follow-up was nominally higher in telemetry
and remote+phone groups (42.2 and 45.3%) compared to the visit group (29.1%).
Overall, >= 1 ICD therapy was delivered to 15.2% of patients. CONCLUSION: In HF
patients with ICDs/CRT-Ds, quarterly remote follow-up only over 12 months was non
inferior to regular personal contact. Addition of quarterly telephone follow-ups
to remote monitoring does not appear to offer any clinical advantage. TRIAL
REGISTRATION: clinicaltrials.gov: NCT01200381 (retrospectively registered on
September 13th 2010).
PMID- 29954341
TI - TDP-43 as a potential biomarker for amyotrophic lateral sclerosis: a systematic
review and meta-analysis.
AB - BACKGROUND: Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS)
are incurable, progressive and fatal neurodegenerative diseases with patients
variably affected clinically by motor, behavior, and cognitive deficits. The
accumulation of an RNA-binding protein, TDP-43, is the most significant
pathological finding in approximately 95% of ALS cases and 50% of FTD cases, and
discovery of this common pathological signature, together with an increasing
understanding of the shared genetic basis of these disorders, has led to FTD and
ALS being considered as part of a single disease continuum. Given the widespread
aggregation and accumulation of TDP-43 in FTD-ALS spectrum disorder, TDP-43 may
have potential as a biomarker in these diseases. METHODS: We therefore conducted
a systematic review and meta-analysis to evaluate the diagnostic utility of TDP
43 detected in the cerebrospinal fluid (CSF) of patients with FTD-ALS spectrum
disorder. RESULTS: From seven studies, our results demonstrate that patients with
ALS have a statistically significantly higher level of TDP-43 in CSF (effect size
0.64, 95% CI: 0.1-1.19, p = 0.02). CONCLUSIONS: These data suggest promise for
the use of CSF TDP-43 as a biomarker for ALS.
PMID- 29954342
TI - LPG: A four-group probabilistic approach to leveraging pleiotropy in genome-wide
association studies.
AB - BACKGROUND: To date, genome-wide association studies (GWAS) have successfully
identified tens of thousands of genetic variants among a variety of
traits/diseases, shedding light on the genetic architecture of complex disease.
The polygenicity of complex diseases is a widely accepted phenomenon through
which a vast number of risk variants, each with a modest individual effect,
collectively contribute to the heritability of complex diseases. This imposes a
major challenge on fully characterizing the genetic bases of complex diseases. An
immediate implication of polygenicity is that a much larger sample size is
required to detect individual risk variants with weak/moderate effects.
Meanwhile, accumulating evidence suggests that different complex diseases can
share genetic risk variants, a phenomenon known as pleiotropy. RESULTS: In this
study, we propose a statistical framework for Leveraging Pleiotropic effects in
large-scale GWAS data (LPG). LPG utilizes a variational Bayesian expectation
maximization (VBEM) algorithm, making it computationally efficient and scalable
for genome-wide-scale analysis. To demonstrate the advantages of LPG over
existing methods that do not leverage pleiotropy, we conducted extensive
simulation studies and applied LPG to analyze two pairs of disorders (Crohn's
disease and Type 1 diabetes, as well as rheumatoid arthritis and Type 1
diabetes). The results indicate that by levelaging pleiotropy, LPG can improve
the power of prioritization of risk variants and the accuracy of risk prediction.
CONCLUSIONS: Our methodology provides a novel and efficient tool to detect
pleiotropy among GWAS data for multiple traits/diseases collected from different
studies. The software is available at
https://github.com/Shufeyangyi2015310117/LPG .
PMID- 29954343
TI - Autoantibodies against neuronal surface proteins in spontaneous subarachnoid and
intracerebral haemorrhage.
AB - BACKGROUND: Brain autoimmunity has been reported in patients with preceding
infection of the central nervous system by herpesviridae. It has been
hypothesized that neuronal damage releasing antigens might trigger secondary
immune response. The objective of the study was to investigate whether brain
damage due to spontaneous subarachnoid haemorrhage (SAH) or intracerebral
haemorrhage (ICH) induces reactivity against neuronal surface proteins. METHODS:
Patients with spontaneous SAH and ICH, who had cerebrospinal fluid (CSF) and
serum sampling within 2 weeks after disease onset (baseline) and afterwards at
least 10 days later (follow-up), were included. Antibodies against NMDA, GABA-B,
AMPA-1/- 2 receptor, LGI1 and CASPR2 were determined by indirect
immunofluorescence. RESULTS: A total of 43 SAH and 11 ICH patients aged 62 (+/
12) years (65% females) had simultaneous CSF/ serum sampling median 5 and 26.5
days after disease onset. At baseline, all CSF samples were collected via
ventricular drainage, at follow-up 20 (37.0%) patients had CSF collection by
lumbar puncture because ventricular drain had been already removed. All CSF and
serum samples at baseline and follow-up tested negative for antibodies against
NMDA, GABA-B, AMPA-1/- 2 receptor, LGI1 and CASPR2. CONCLUSIONS: Immunoreactivity
against common neuronal surface proteins was not observed within the early
disease course of spontaneous SAH and ICH.
PMID- 29954344
TI - Uptake of hepatitis B vaccination and its determinants among health care workers
in a tertiary health facility in Enugu, South-East, Nigeria.
AB - BACKGROUND: Hepatitis B vaccination is the most effective method of prevention
for hepatitis B virus infection. It is a major public health problem in Nigeria,
and health workers are at increased risk. This study determined the uptake of
hepatitis B vaccination and assessed its determinants among health care workers
(HCWs). METHODS: A hospital-based cross-sectional study was conducted between
July and August, 2016 using self-administered structured questionnaires among
3132 HCWs in University of Nigeria Teaching Hospital, Enugu, South-East, Nigeria.
Data was analysed using SPSS version 22. Binary logistic regression analysis was
used to identify factors that influenced uptake of vaccination. Ethical clearance
was obtained from the Research Ethics Committee of the health facility. RESULTS:
The uptake of hepatitis B vaccination was 14.2% (n = 445). The number of doses
received were: 3 doses (218/3132, 48.9%), 2 doses (71/3132, 16.0%), and one dose
(156/3132, 35.1%). The reasons for non-uptake of vaccination included: cost of
vaccine 48 (10.8%), 'did not believe they could be infected' 28 (6.6%), long
vaccination schedule, and lack of time 150 (35.1%). The Odds for uptake of
hepatitis B vaccination were 22% lower among nurses compared to doctors (AOR =
0.78, 95% CI = 0.54-0.98, P = 0.037). It increased with increasing age (AOR =
1.30, 95% CI = 1.08-1.59, P < 0.001), increasing duration of work in the
hospital (AOR = 1.19, 95% CI = 1.09-1.32, P = 0.032), and was about twice higher
among those that had tertiary education than others that had less education (AOR
= 1.96, 95 CI = 0.76-5.07, P = 0.164). CONCLUSIONS: The uptake of hepatitis B
vaccination was low among HCWs in Enugu, Nigeria. Age, staff category, and
duration of work in the hospital, were independently associated with hepatitis B
vaccination. Provision of adequate hepatitis B surface antigen screening
facilities and vaccination sites where the cost of vaccination is subsidized for
all HCWs is recommended.
PMID- 29954345
TI - Rituximab induction therapy for de novo ANCA associated vasculitis in pregnancy:
a case report.
AB - BACKGROUND: The diagnosis of antineutrophil cytoplasmic antibody (ANCA)
associated vasculitis (AAV) is rare in pregnancy but potentially life
threatening. There are no randomized controlled trials to guide the management of
AAV in pregnancy and fetal safety data remains limited. Rituximab administration,
a treatment for AAV, has been reported in pregnant women with reassuring fetal
outcomes in the oncology and rheumatology literature; however, no published
reports describe its use in AAV. CASE PRESENTATION: We present a case of de novo
myeloperoxidase positive (MPO) AAV diagnosed at 22 weeks gestation. Clinical
presentation included elevated serum creatinine at 177 MUmol/L, hematuria and
nephrotic range proteinuria along with high-titre MPO. Diagnosis was confirmed by
renal biopsy. Patient was treated with methylprednisolone IV followed by oral
prednisone 70 mg daily and Rituximab 650 mg IV weekly for four weeks followed by
azathioprine maintenance therapy and prednisone taper. Delivery occurred at 29
weeks gestation via cesarean section for maternal neurologic symptoms concerning
for preeclampsia. Maternal and fetal CD + 19 cells were depleted at time of
delivery with associated fetal lymphopenia in the absence of infection or other
complications related to Rituximab use. The patient experienced a reduction in
proteinuria and inflammatory markers following Rituximab therapy; however, serum
creatinine increased to 375 MUmol/L by 11 weeks post-partum. CONCLUSION: We
report the first use, to our knowledge, of Rituximab with corticosteroids for
induction therapy of AAV in pregnancy.
PMID- 29954346
TI - The natural course of nonculprit coronary artery lesions; analysis by serial
quantitative coronary angiography.
AB - BACKGROUND: Nonculprit lesions are the major cause of future cardiovascular
events. However, the natural course of nonculprit lesions and angiographic
predictors of plaque progression are not well-studied. The purpose of our study
was to observe the natural course of nonculprit lesions, and to identify
predictors of unanticipated future events and angiographic progression in
nonculprit lesions. METHODS: We analyzed 640 nonculprit lesions with a length of
>=2 mm and luminal narrowing >=30% from 320 patients who had two serial
angiographic follow-ups; 9 to 13 months post-PCI and 24 months post-PCI. The
study endpoints were nonculprit-ischemia driven revascularization (IDR) and the
rate of diameter stenosis (DS) progression. Those with progression of DS >
12%/year were defined as 'rapid progressors'. RESULTS: During the median follow
up period of 737 days, 20 lesions in 20 patients (6.3%) required nonculprit-IDR.
Independent predictors of nonculprit-IDR were diabetes (hazard ratio [HR] 2.93,
95% confidence interval [CI] 1.072-8.007, p = 0.036) and lesion type B2/C (HR
4.017, 95% CI 1.614-9.997, p = 0.003). The presence of one or both of the two
major risk factors was associated with significant DS progression (3.0 +/- 6.8%
vs. 3.5 +/- 6.1% vs. 6.8 +/- 9.9% for lesions with 0, 1 and both risk factors, p
< 0.001). Among the 640 lesions, 38 lesions (5.9%) in 33 patients were rapid
progressors, while risk factors of rapid progressors included lesion type B2/C as
a lesion-related risk factor (HR 1.998, 95% CI 1.006-3.791, p = 0.048) and
diabetes mellitus as a patient-related risk factor (HR 3.725, 95% CI 1.937-7.538,
p < 0.001). Lesions with both risk factors (type B2/C lesions in diabetic
patients) were at the highest risk of rapid progression (odds ratio 3.250, 95% CI
1.451-7.282), compared to type A/B1 lesions in non-diabetic patients. CONCLUSION:
Nonculprit-IDR was not uncommon during the 2-year follow up period in our
population. The major risk factors of nonculprit lesion progression were diabetes
and lesion type B2/C. TRIAL REGISTRATION: Retrospectively registered and approved
by the institutional review board of Seoul National University Hospital (No.:
1801-138-918) on February 2nd, 2018.
PMID- 29954347
TI - DNA sequence-based re-assessment of archived Cronobacter sakazakii strains
isolated from dairy products imported into China between 2005 and 2006.
AB - BACKGROUND: Cronobacter species are associated with severe foodborne infections
in neonates and infants, with particular pathovars associated with specific
clinical presentations. However, before 2008 the genus was regarded as a single
species named Enterobacter sakazakii which was subdivided into 8 phenotypes. This
study re-analyzed, using multi-locus sequence typing (MLST) and whole genome
sequence with single nucleotide polymorphism analysis (WGS-SNP), 52 strains which
had been identified as Enterobacter sakazakii as according to the convention at
the time of isolation. These strains had been isolated from dairy product imports
into China from 9 countries between 2005 and 6. Bioinformatic analysis was then
used to analyze the relatedness and global dissemination of these strains.
RESULT: FusA allele sequencing revealed that 49/52 strains were Cronobacter
sakazakii, while the remaining 3 strains were Escherichia coli, Enterobacter
cloacae, and Franconibacter helveticus. The C. sakazakii strains comprised of 8
sequence types (STs) which included the neonatal pathovars ST1, ST4 and ST12. The
predominant sequence type was ST13 (65.3%, 32/49) which had been isolated from
dairy products imported from 6 countries. WGS-SNP analysis of the 32 C. sakazakii
ST13 strains revealed 5 clusters and 5 unique strains which did not correlate
with the country of product origin. CONCLUSION: The mis-identification of E.
coli, E. cloacae and F. helveticus as Cronobacter spp. reinforces the need to
apply reliable methods to reduce the incidence of false positive and false
negative results which may be of clinical significance. The WGS-SNP analysis
demonstrated that indistinguishable Cronobacter strains within a sequence type
can be unrelated, and may originate from multiple sources. The use of WGS-SNP
analysis to distinguishing of strains within a sequence type has important
relevance for tracing the source of outbreaks due to Cronobacter spp.
PMID- 29954348
TI - "Well, not me, but other women do not register because..."- Barriers to seeking
antenatal care in the context of prevention of mother-to-child transmission of
HIV among Zimbabwean women: a mixed-methods study.
AB - BACKGROUND: While barriers to uptake of antenatal care (ANC) among pregnant women
have been explored, much less is known about how integrating prevention of mother
to-child transmission (PMTCT) programmes within ANC services affects uptake. We
explored barriers to uptake of integrated ANC services in a poor Zimbabwean
community. METHODS: A cross-sectional survey was conducted among post-natal women
at Mbare Clinic, Harare, between September 2010 and February 2011. Collected data
included participant characteristics and ANC uptake. Logistic regression was
conducted to determine factors associated with ANC registration. In-depth
interviews were held with the first 21 survey participants who either did not
register or registered after twenty-four weeks gestation to explore barriers.
Interviews were analysed thematically. RESULTS: Two hundred and ninety-nine
participants (mean age 26.1 years) were surveyed. They came from ultra-poor
households, with mean household income of US$181. Only 229 (76.6%) had registered
for ANC, at a mean gestation of 29.5 weeks. In multivariable analysis, household
income was positively associated with ANC registration, odds ratio (OR) for a $10
increase in household income 1.02 (95% confidence interval, CI, 1.0-1.04), as was
education which interacted with having planned the pregnancy (OR for planned
pregnancy with completed ordinary level education 3.27 (95%CI 1.55-6.70).
Divorced women were less likely to register than married women, OR 0.20 (95%CI
0.07-0.58). In the qualitative study, barriers to either ANC or PMTCT services
limited uptake of integrated services. Women understood the importance of
integrated services for PMTCT purposes and theirs and the babies' health and
appeared unable to admit to barriers which they deemed "stupid/irresponsible",
namely fear of HIV testing and disrespectful treatment by nurses. They
represented these commonly recurring barriers as challenges that "other women"
faced. The major proffered personal barrier was unaffordability of user fees,
which was sometimes compounded by unsupportive husbands who were the
breadwinners. CONCLUSION: Women who delayed/did not register were aware of the
importance of ANC and PMTCT but were either unable to afford or afraid to
register. Addressing the identified challenges will not only be important for
integrated PMTCT/ANC services but will also provide a model for dealing with
challenges as countries scale up 'treat all' approaches.
PMID- 29954349
TI - Cataract surgery combined with micro-incision vitrectomy in patients with
behcet's disease uveitis.
AB - BACKGROUND: This study sought to report the outcomes of a combined cataract
extraction, intraocular lens (IOL) insertion and micro-incision vitrectomy (MIVS)
procedure for the treatment of Behcet uveitis. METHODS: This investigation
involved the retrospective evaluation of a case series of patients with Behcet
uveitis who underwent cataract extraction, IOL insertion and MIVS in a single
surgical session at the same institution between January 2013 and November 2016.
Outcome measures included visual acuity, inflammatory reaction, systemic anti
inflammatory medications, intraocular pressure (IOP) and complications. RESULTS:
Seven eyes of seven patients with a mean age of 39.00 +/- 5.54 years (range, 32
to 48 years) and a mean follow-up duration of 13.57 +/- 5.83 months (range, 6 to
24 months) were studied; five patients with a history of well-controlled uveitis
were included. All patients underwent cataract extraction and IOL implantation
combined with MIVS. All patients received postoperative steroids, which were
slowly tapered during the weeks after surgery. There were no significant
complications related to the surgery. Overall, best-corrected visual acuity
(BCVA) was improved from log MAR (logarithm of the minimum angle of resolution)
1.67 +/- 0.67 preoperatively to log MAR 0.74 +/- 0.35 postoperatively; this
improvement was statistically significant (p < 0.05). All eyes were deemed quiet
at follow-up, and no patients required the escalation of therapy for long-term
uveitis control. CONCLUSIONS: This retrospective series indicates that a
procedure that combines phacoemulsification, IOL implantation and MIVS is a
feasible technique for the removal of cataracts and pathologic vitreous in eyes
with Behcet uveitis. This approach can restore vision without obvious
complications.
PMID- 29954350
TI - Characterizing the demographics of chronic pain patients in the state of Maine
using the Maine all payer claims database.
AB - BACKGROUND: Chronic pain is currently a significant health problem in the United
States. A comprehensive strategy is needed to increase prevention of chronic pain
and to improve care for chronic pain patients. However, development of a
successful strategy relies, in part, on a better understanding of the
demographics and socioeconomics of patients living with chronic pain conditions.
The current study was designed to understand the burden of chronic pain in the
state of Maine by identifying the prevalence of chronic pain and its relationship
with selected demographic and socioeconomic factors in Maine. METHODS: The Maine
All Payer Claims Database (MEAPCD) (2006-2011) was used in the secondary data
analysis to assess the demographic characteristics (such as age, sex, insurance
type, and county of residence) of chronic pain patients in Maine. Chronic pain
patients were identified based on the presence of pre-identified chronic pain
associated ICD-9 code(s) and opioid prescription information. Potential
associations between the prevalence of chronic pain and a number of socioeconomic
factors were determined by comparisons to Maine Census data. RESULTS: More women
in the state were identified as having chronic pain across all counties and all
age groups (> 10 years old). Surprisingly, the majority of chronic pain patients
were identified based on the diagnostic code criteria and not the opioid
prescription criteria. A greater utilization of public health insurance was seen
within the chronic pain patients. At the county level, although neither education
level nor income were associated with the prevalence of chronic pain, these
factors significantly correlated with the usage of public health insurance.
CONCLUSIONS: Further detailed characterization of the chronic pain patient
population in the state of Maine, using multiple data sources, can help design
population-targeted strategies to prevent and manage chronic pain.
PMID- 29954351
TI - Differences in infant feeding practices between Chinese-born and Australian-born
mothers living in Australia: a cross-sectional study.
AB - BACKGROUND: Chinese immigrants are the third largest immigrant group in
Australia. Recent qualitative evidence from Victorian Maternal and Child Health
nurses indicate that infants of Chinese parents commonly have rapid growth
trajectories and that high value is placed on rapid growth and having a fatter
child; with low breastfeeding rates and overfeeding of infant formula. The aim of
this study was to compare infant feeding practices (breastfeeding, infant
formula, other liquids, solids) of Chinese-born and Australian-born mothers
living in Australia. METHODS: Using the Australian National Infant Feeding Survey
dataset (2010-2011), infant feeding data from Chinese-born mothers (n = 602) were
compared with a random sub-sample of Australian-born mothers (n = 602). Group
differences on feeding practices were tested using Chi-square or t-tests and the
effect of ethnicity on infant feeding behaviours assessed using regression.
RESULTS: Compared to infants of Australian-born mothers, infants of Chinese-born
mothers were younger when they first consumed infant formula, water-based drinks
and fruit juice and older when they first ate solid foods (p < 0.05).
Furthermore, infants of Chinese-born mothers were less likely to have ever had
cow's milk (OR: 0.37 95%CI:, 0.18-0.78) and solids (0.41, 0.25-0.68); but were
more likely to have ever had infant formula (2.19, 1.32-3.62), water (2.45, 1.55
3.87), toddler milk (3.39, 1.60-7.18), water-based drinks (e.g. cordial, soft
drink, tea; 2.48, 1.12-5.49), and fruit juice (4.03, 2.50-6.51). Those <=4 months
of age were more likely to have had water-based drinks (7.77, 1.96-30.77) and
fruit juice (3.44, 1.14-10.38) (p < 0.05) compared to infants of Australian-born
mothers. CONCLUSION: Differences in mothers' early infant feeding practices exist
between Chinese-born and Australian-born mothers living in Australia. Better
understanding these ethnically patterned infant feeding practices is important
for identifying key opportunities to promote best nutrition and growth in early
life in different ethnic groups within our population.
PMID- 29954352
TI - Highly suspected primary intraocular lymphoma in a patient with rheumatoid
arthritis treated with etanercept: a case report.
AB - BACKGROUND: To describe a case of highly suspected primary intraocular lymphoma
(PIOL) in a patient using etanercept for the treatment of rheumatoid arthritis.
CASE PRESENTATION: A 50-year-old female patient presented with decreased vision
in her left eye that lasted for a week. She had a 15-year history of seropositive
rheumatoid arthritis (RA), and had been taking weekly etanercept for the
preceding 8 months. Funduscopic examination and SD-OCT showed a swollen ellipsoid
zone (EZ) and a retinal pigment epithelium (RPE) irregularity of the right eye.
We also noted EZ disruption and a RPE irregularity in the left eye. As subretinal
infiltration was aggravated in the right eye after the initial treatment, we
completed a vitrectomy. Vitreous cytology revealed PIOL with positive CD20
immunostaining. She was treated with serial intravitreal methotrexate injections
and systemic chemotherapy. After the treatment, subretinal infiltration and
subRPE deposits were decreased in the right eye with no evidence of recurrence in
either eye. CONCLUSIONS: This case suggests a potential relationship between
immunosuppression with anti-TNFalpha medication, and increased risk for lymphoma,
especially in patients with underlying rheumatologic disorders and especially in
patients with suspected chronic refractory uveitis.
PMID- 29954353
TI - Effects of vitamin D supplementation on the outcomes of patients with pulmonary
tuberculosis: a systematic review and meta-analysis.
AB - BACKGROUND: Vitamin D is involved in the host immune response toward
Mycobacterium tuberculosis. However, the efficacy of vitamin D supplementation on
sputum conversion, clinical response to treatment, adverse events, and mortality
in patients with pulmonary tuberculosis (PTB) remains controversial. We aimed to
clarify the efficacy and safety of vitamin D supplementation in PTB treatment.
METHODS: We searched Medline, Embase, Cochrane Central Register of Controlled
Trials, Web of Science for double-blind, randomized controlled trials of vitamin
D supplementation in patients with PTB that reported sputum conversion, clinical
response to treatment, adverse events, or mortality, published from database
inception to November 26, 2017. This study was registered with PROSPERO, number
CRD42018081236. RESULTS: A total of 1787 patients with active PTB receiving
vitamin D supplementation along with standard anti-tuberculosis regimen were
included in the eight trials with different doses of vitamin D ranging from 1000
IU/day to 600,000 IU/month at different intervals. Primary analysis revealed that
vitamin D supplementation increased the proportion of sputum smear and culture
conversions (OR 1.21, 95%CI 1.05~ 1.39, z = 2.69, P = 0.007; OR 1.22, 95%CI 1.04~
1.43, z = 2.41, P = 0.02), but did not improve the time to sputum smear and
culture conversions (HR 1.07, 95%CI 0.83~ 1.37, z = 0.50, P = 0.62; HR 0.97,
95%CI 0.76~ 1.23, z = 0.29, P = 0.77). In the secondary analysis, vitamin D
improved serum 25(OH)D, plasma calcium concentration, lymphocyte count, and chest
radiograph (MD 103.36, 95%CI 84.20~ 122.53, z = 10.57, P < 0.00001; SMD 0.26,
95%CI 0.15~ 0.37, z = 4.61, P < 0.00001; MD 0.09, 95%CI 0.03~ 0.14, z = 2.94, P =
0.003); MD -0.33, 95% CI -0.57~ - 0.08 z = 2.57, P = 0.01), but had no impact on
adverse events, mortality and other indicators(TB score, BMI, mean mid-upper arm
circumference, weight gain, CRP, ESR, and other blood cells) (P > 0.05).
CONCLUSIONS: Vitamin D supplementation can be considered as a combination therapy
in patients with PTB.
PMID- 29954354
TI - A randomized controlled double-blind clinical trial comparing versus placebo the
effect of an edible algal extract (Ulva Lactuca) on the component of depression
in healthy volunteers with anhedonia.
AB - BACKGROUND: The effects of the seaweed extract were evaluated on the animal model
equivalent of depression compared with a control group treated with the carrier
(spring water) and a reference group treated with Imipramine and showed
significative effect. This clinical trial was intended to confirm in humans the
potential efficacy identified in animals. The primary objective was to compare
against a placebo the effect of Ulva L.L extract in healthy volunteers whose
anhedonia was characterized by a component of depression. METHODS: Single-centre
double-blind randomized placebo-controlled clinical trial on parallel arms of two
groups of 45 subjects. The study could include men or women aged 18 to 65 years
with anhedonia characterized by a Snaith Hamilton Pleasure Scale score (SHAPS) of
>=5 and feeling low morale for at least four weeks characterized by a component
of depression evaluated on the Quick Inventory of Depressive Symptomatology -
Self Report (QIDS-SR). Evaluation criteria: QIDS-SR; Patient Global Improvement
Impression (PGII) and Clinical Global Improvement Impression (CGII). RESULTS: 86
subjects were included in the trial: 42 in the placebo group and 44 Ulva group.
At D84, QIDS-SR significantly decreased more in the Ulva.L.L. group than in the
placebo group (p: 0.0389). This difference is essentially linked to an
improvement of the sleep disorders (p: 0.0219), of the psychomotor consequences
(p: 0.002) and of the nutrition behaviour (p: 0.0694). 90.1% have the feeling of
being improved in the Ulva group vs 72.5% in the placebo group (p: 0.0114) and in
parallel 90.9% of the practitioners have the feeling that the subject has
improved vs 70.8% (p: 0.0214). CONCLUSION: This double-blind randomized placebo
controlled trial shows that daily intake for three months of a water-soluble
extract of Ulva L.L. continues to significantly improve the component of
depression of subjects presenting anhedonia compared with a placebo. TRIAL
REGISTRATION: Trial retrospectively registred on ClinicalTrial.gov under ID:
NCT03545399 Date: 05/22/2018.
PMID- 29954357
TI - Can internal tobacco industry documents be useful for studying the UK alcohol
industry?
AB - BACKGROUND: The release of internal documents now available in the Truth Tobacco
Documents Library has offered important insights into the machinations of tobacco
companies. These documents potentially offer additional insights into the nature
of the alcohol industry, due to co-ownership and collaborative working across
industries. This proof of concept study aims to build on the few examples of
internal tobacco company documents being used to study alcohol industry
activities, to identify the scope of information available on the UK alcohol
industry. METHODS: We identified the principal company names of the major
national brewers, including predecessor company names, until the late 1990s,
contemporaneous to the bulk of the tobacco documents. Using these names as
initial search terms, we searched the Library to identify relevant material.
Documents returned were then analysed for evidence of alcohol industry
connections to the tobacco industry in the UK. RESULTS: We found evidence of
significant relationships between the two industries including previously
unidentified data on co-ownership and cross industry shareholding; informal help
seeking between sectors; collaboration on issues of common interest; and cross
industry ties via third party service providers, membership of common
organisations and participation in shared events and platforms. CONCLUSIONS:
These findings call for further research to analyse in greater depth the
information identified here, and to explore alcohol industry activities and links
with tobacco companies in other national contexts. This preliminary investigation
suggests there is much valuable data available in the Truth Tobacco Documents
Library that can serve to guide research on the alcohol industry.
PMID- 29954356
TI - Incidence of postpartum infection, outcomes and associated risk factors at
Mbarara regional referral hospital in Uganda.
AB - BACKGROUND: There is a paucity of recent prospective data on the incidence of
postpartum infections and associated risk factors in sub-Saharan Africa.
Retrospective studies estimate that puerperal sepsis causes approximately 10% of
maternal deaths in Africa. METHODS: We enrolled 4231 women presenting to a
Ugandan regional referral hospital for delivery or postpartum care into a
prospective cohort and measured vital signs postpartum. Women developing fever (>
38.0 degrees C) or hypothermia (< 36.0 degrees C) underwent symptom
questionnaire, structured physical exam, malaria testing, blood, and urine
cultures. Demographic, treatment, and post-discharge outcomes data were collected
from febrile/hypothermic women and a random sample of 1708 normothermic women.
The primary outcome was in-hospital postpartum infection. Multivariable logistic
regression was used to determine factors independently associated with postpartum
fever/hypothermia and with confirmed infection. RESULTS: Overall, 4176/4231 (99%)
had >=1 temperature measured and 205/4231 (5%) were febrile or hypothermic. An
additional 1708 normothermic women were randomly selected for additional data
collection, for a total sample size of 1913 participants, 1730 (90%) of whom had
complete data. The mean age was 25 years, 214 (12%) were HIV-infected, 874 (51%)
delivered by cesarean and 662 (38%) were primigravidae. Among febrile/hypothermic
participants, 174/205 (85%) underwent full clinical and microbiological
evaluation for infection, and an additional 24 (12%) had a partial evaluation.
Overall, 84/4231 (2%) of participants met criteria for one or more in-hospital
postpartum infections. Endometritis was the most common, identified in 76/193
(39%) of women evaluated clinically. Twenty-five of 175 (14%) participants with
urinalysis and urine culture results met criteria for urinary tract infection.
Bloodstream infection was diagnosed in 5/185 (3%) participants with blood culture
results. Another 5/186 (3%) tested positive for malaria. Cesarean delivery was
independently associated with incident, in-hospital postpartum infection (aOR
3.9, 95% CI 1.5-10.3, P = 0.006), while antenatal clinic attendance was
associated with reduced odds (aOR 0.4, 95% CI 0.2-0.9, P = 0.02). There was no
difference in in-hospital maternal deaths between the febrile/hypothermic (1,
0.5%) and normothermic groups (0, P = 0.11). CONCLUSIONS: Among rural Ugandan
women, postpartum infection incidence was low overall, and cesarean delivery was
independently associated with postpartum infection while antenatal clinic
attendance was protective.
PMID- 29954355
TI - Association between first caesarean delivery and adverse outcomes in subsequent
pregnancy: a retrospective cohort study.
AB - BACKGROUND: Few studies have explored the association between a previous
caesarean section (CS) and adverse perinatal outcomes in a subsequent pregnancy,
especially in women who underwent a non-indicated CS in their first delivery. We
designed this study to compare the perinatal outcomes of a subsequent pregnancy
in women who underwent spontaneous vaginal delivery (SVD) or CS in their first
delivery. METHODS: This retrospective cohort study included women who underwent
singleton deliveries at the International Peace Maternity and Child Health
Hospital from January 2013 to December 2016. Data on the perinatal outcomes of
all the women were extracted from the medical records. Multivariate logistic
regression was conducted to assessed the association between CS in the first
delivery and adverse perinatal outcomes in the subsequent pregnancy. RESULTS: CS
delivery in the subsequent pregnancy was more likely for women who underwent CS
in their first birth than for women with previous SVD (97.3% versus 13.2%). CS in
the first birth was also associated with a significantly increased risk of
adverse outcomes in the subsequent pregnancy, especially in women who underwent a
non-indicated CS. Adverse perinatal outcomes included pregnancy-induced
hypertension [adjusted odds ratio (OR), 95% confidence interval (CI): 2.20, 1.59
3.05], gestational diabetes mellitus (1.82, 1.57-2.11), gestational anaemia
(1.27, 1.05-1.55), placenta previa (3.18, 2.15-4.71), placenta accreta (2.75,
1.75-4.31), and polyhydramnios (2.60, 1.57-4.31) in the mother and preterm
delivery (1.37, 1.06-1.78), low birth weight (3.78, 2.07-6.90), macrosomia (5.04,
3.95-6.44), and neonatal jaundice (1.72, 1.39-2.14) in the baby. CONCLUSIONS: CS
in the first delivery markedly increases the risk of repeated CS and maternal
fetal complications in the subsequent pregnancy, especially in women with a non
indicated CS.
PMID- 29954358
TI - Efficacy after preoperative capecitabine and oxaliplatin (XELOX) versus
docetaxel, oxaliplatin and S1 (DOS) in patients with locally advanced gastric
adenocarcinoma: a propensity score matching analysis.
AB - BACKGROUND: The aim of this study was to compare the efficacies of the XELOX and
DOS regimens as preoperative chemotherapy in patients with locally advanced
gastric cancer. METHODS: All cases of locally advanced gastric cancer treated
with the XELOX or DOS regimen were reviewed retrospectively. Propensity score
matching (PSM) was carried out to reduce selection bias based on age, gender,
location, Lauren type, carcinoembryonic antigen level, clinical tumor stage, and
clinical node stage. RESULTS: From January 2010 to December 2016, 248 patients
were matched; 159 of them received the XELOX regimen and 89 the DOS regimen. The
response rates in the XELOX and DOS groups were 34.5 and 38.1%, respectively (P =
0.823). After four cycles of chemotherapy, 111 patients (69.8%) in the XELOX
group and 65 patients (73.0%) in the DOS group underwent radical surgery (P =
0.485). The median progression-free survival (33.0 months vs. 18.7 months, P =
0.0356) and the median overall survival (43.8 months vs. 29.1 months, P = 0.0003)
were longer for patients who received the DOS regimen than for those who received
the XELOX regimen. The occurrence of grade 3 to 4 toxicity was similar in the two
groups. CONCLUSIONS: For locally advanced gastric cancer patients, the DOS
regimen showed more benefit than the XELOX regimen as preoperative chemotherapy,
without any added toxicity effects.
PMID- 29954359
TI - Evaluation of inhaler technique and achievement and maintenance of mastery of
budesonide/formoterol Spiromax(r) compared with budesonide/formoterol
Turbuhaler(r) in adult patients with asthma: the Easy Low Instruction Over Time
(ELIOT) study.
AB - BACKGROUND: Incorrect inhaler technique is a common cause of poor asthma control.
This two-phase pragmatic study evaluated inhaler technique mastery and
maintenance of mastery with DuoResp(r) (budesonide-formoterol [BF]) Spiromax(r)
compared with Symbicort(r) (BF) Turbuhaler(r) in patients with asthma who were
receiving inhaled corticosteroids/long-acting beta2-agonists. METHODS: In the
initial cross-sectional phase, patients were randomized to a 6-step training
protocol with empty Spiromax and Turbuhaler devices. Patients initially
demonstrating >=1 error with their current device, and then achieving mastery
with both Spiromax and Turbuhaler (absence of healthcare professional [HCP]
observed errors), were eligible for the longitudinal phase. In the longitudinal
phase, patients were randomized to BF Spiromax or BF Turbuhaler. Co-primary
endpoints were the proportions of patients achieving device mastery after three
training steps and maintaining device mastery (defined as the absence of HCP
observed errors after 12 weeks of use). Secondary endpoints included device
preference, handling error frequency, asthma control, and safety. Exploratory
endpoints included assessment of device mastery by an independent external expert
reviewing video recordings of a subset of patients. RESULTS: Four hundred ninety
three patients participated in the cross-sectional phase, and 395 patients in the
longitudinal phase. In the cross-sectional phase, more patients achieved device
mastery after three training steps with Spiromax (94%) versus Turbuhaler (87%)
(odds ratio [OR] 3.77 [95% confidence interval (CI) 2.05-6.95], p < 0.001).
Longitudinal phase data indicated that the odds of maintaining inhaler mastery at
12 weeks were not statistically significantly different (OR 1.26 [95% CI 0.80
1.98], p = 0.316). Asthma control improved in both groups with no significant
difference between groups (OR 0.11 [95% CI -0.09-0.30]). An exploratory analysis
indicated that the odds of maintaining independent expert-verified device mastery
were significantly higher for patients using Spiromax versus Turbuhaler (OR 2.11
[95% CI 1.25-3.54]). CONCLUSIONS: In the cross-sectional phase, a significantly
greater proportion of patients using Spiromax versus Turbuhaler achieved device
mastery; in the longitudinal phase, the proportion of patients maintaining device
mastery with Spiromax versus Turbuhaler was similar. An exploratory independent
expert-verified analysis found Spiromax was associated with higher levels of
device mastery after 12 weeks. Asthma control was improved by treatment with both
BF Spiromax and BF Turbuhaler. TRIAL REGISTRATION: EudraCT 2013-004630-14
(registration date 23 January 2014); NCT02570425 .
PMID- 29954360
TI - Measuring sexual behaviour in Malawi: a triangulation of three data collection
instruments.
AB - BACKGROUND: There is a need for valid approaches to measure sexual interactions
to assess the impact of behavioural interventions and to predict the impact of
behaviour changes. Different methods of asking about sexual behaviour often yield
conflicting answers and men often report higher levels of heterosexual activity
than women. To better understand self-reported sexual behaviour data and how best
to collect it, we analyzed data collected as part of a larger project (ST
IMPACTS) on the social and behavioural impact of introducing community-level HIV
self-testing (HIVST) with counseling (semi-supervised with pre- and generic post
test counseling provided on delivery or collection of test kits) in an urban
Malawian setting. METHODS: Information on sexual behaviour was collected from HIV
self-testers over a three-month period. Three different methods were used:
retrospective face-to-face interviews (FTFI); audio computer assisted self
interviews (ACASI) and a prospective coital diary. Both retrospective instruments
were used before and after the three-month study period. Frequency and cross
tabulation, as well as scatterplots, were used for exploratory analyses. Chi
square tests were used to test for differences in proportions. Spearman's
correlation coefficient was used to explore associations between both continuous
and ordinal variables and Wilcoxon's paired sample and Mann-Whitney test was used
to test for differences in such variables or between variables. RESULTS: There
was reasonable agreement between the two retrospective methods although both
yielded inconsistent answers e.g. with lower reported numbers of life-time sexual
partners at the end than at the beginning of the study period. The diary method
elicited higher reported levels of sex with multiple partners than both
retrospective instruments which may be due to inadequate recall. Over the study
period 37.4% of men and 19.7% of women reported multiple sexual partners using
the diary. There was no clear relationship between reported sexual behaviour and
HIV status (prevalence 9.6%). CONCLUSIONS: Diaries may therefore have higher
validity for sensitive behaviour reporting and thus be the preferred method in
similar African contexts in measuring sexual behaviours.
PMID- 29954361
TI - Prevalence of depression and anxiety among participants with glaucoma in a
population-based cohort study: The Gutenberg Health Study.
AB - BACKGROUND: To investigate the prevalence of depression and anxiety among
subjects with self-reported glaucoma and the association between self-reported
glaucoma and depression respectively anxiety in a European cohort. METHODS: A
study sample of 14,657 participants aged 35 to 74 years was investigated in a
population-based cohort study. All participants reported presence or absence of
glaucoma. Ophthalmological examinations were carried out in all participants and
demographic and disease related information were obtained by interview.
Depression was assessed with the Patient Health Questionnaire (PHQ-9), and
generalized anxiety with the two screening items (GAD-2) of the short form of the
GAD-7 (Generalized Anxiety Disorder-7 Scale). Prevalence of depression and
generalized anxiety were investigated for subjects with and without self-reported
glaucoma. Logistic regression analyses with depression, respectively anxiety as
dependent variable and self-reported glaucoma as independent variable were
conducted and adjusted for socio-demographic factors, systemic comorbidities
(arterial hypertension, myocardial infarction, stroke, diabetes mellitus, chronic
obstructive pulmonary disease, cancer), ocular diseases (cataract, macular
degeneration, corneal diseases, diabetic retinopathy), visual acuity, intraocular
pressure, antiglaucoma eye drops (sympathomimetics, parasympathomimetics,
carbonic anhydrase inhibitors, beta-blockers, prostaglandins) and general health
status. RESULTS: 293 participants (49.5% female) reported having glaucoma.
Prevalence of depression among participants with and without self-reported
glaucoma was 6.6% (95%-CI 4.1-10.3) respectively 7.7% (95%-CI 7.3-8.2), and for
anxiety 5.3% (95%-CI 3.1-8.7) respectively 6.6% (95%-CI 6.2-7.1). Glaucoma was
not associated with depression (Odds ratio 1.10, 95%-CI 0.50-2.38, p = 0.80) or
anxiety (1.48, 95%-CI 0.63-3.30, p = 0.35) after adjustment for socio-demographic
factors, ocular/systemic diseases, ocular parameters, antiglaucoma drugs and
general health status. A restriction to self-reported glaucoma cases either
taking topical antiglaucoma medications or having a history of glaucoma surgery
did not alter the result. CONCLUSIONS: This is the first study analyzing both
depression and anxiety among glaucoma patients in a European cohort. Subjects
with and without self-reported glaucoma had a similar prevalence of depression
and anxiety in our population-based sample. Self-reported glaucoma was not
associated with depression or anxiety. A lack of a burden of depressive symptoms
may result from recruitment from a population-based sample as compared to
previous study groups predominantly recruited from tertiary care hospitals.
PMID- 29954362
TI - Phase II trial of eribulin mesylate as a first- or second-line treatment for
locally advanced or metastatic breast cancer: a multicenter, single-arm trial.
AB - BACKGROUND: Eribulin mesylate is currently indicated as a sequential monotherapy
to be administered after two chemotherapeutic regimens, including anthracycline
and taxane treatments, for treatment of metastatic breast cancer. This open
label, multicenter phase II study was designed to evaluate the efficacy and
safety of eribulin as a first- or second-line treatment for patients with
metastatic breast cancer. METHODS: The primary objective was to determine the
overall response rate. Secondary objectives were to evaluate progression-free
survival and the safety profile. Patients were scheduled to receive eribulin
mesylate 1.4 mg/m2 intravenously on days 1 and 8 of a 21-day cycle. Patients
received the study treatment unless disease progression, unacceptable toxicity,
or a request to discontinue from the patient and/or investigator eventuated.
RESULTS: Between December 2012 and September 2015, 32 patients with metastatic
breast cancer were enrolled at 10 participating clinical institutions in Japan,
and toxicity and response rates were evaluated. The overall response rate was
43.8% (95% confidence interval [CI] 26.5-61.0). The clinical benefit and tumor
control rates were 56.3% (95% CI 39.0-73.5) and 78.1% (95% CI 63.8-92.5),
respectively. Median progression-free survival was 8.3 months (95% CI 7.1-9.4). A
subgroup analysis did not identify any factors affecting the efficacy of
eribulin. The most common adverse events were neutropenia (71.9%), alopecia
(68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy,
eribulin showed sufficient efficacy for metastatic breast cancer compared with
taxane and capecitabine treatment in previous clinical trials. The safety profile
of eribulin was acceptable. CONCLUSIONS: Eribulin may be another option for first
line chemotherapeutic regimens for metastatic breast cancer. TRIAL REGISTRATIONS:
This trial was retrospectively registered at the University Hospital Medical
Information Network (UMIN) Clinical Trial Registry (ID number: UMIN000010334 ).
Date of trial registration: April 1st, 2013.
PMID- 29954363
TI - Real-world health outcomes in adults with moderate-to-severe psoriasis in the
United States: a population study using electronic health records to examine
patient-perceived treatment effectiveness, medication use, and healthcare
resource utilization.
AB - BACKGROUND: Little is known regarding real-world health outcomes data among US
psoriasis patients, but electronic health records (EHR) that collect structured
data at point-of-care may provide opportunities to investigate real-world health
outcomes among psoriasis patients. Our objective was to investigate patient
perceived treatment effectiveness, patterns of medication use (duration,
switching, and/or discontinuation), healthcare resource utilization, and
medication costs using real-world data from psoriasis patients. METHODS: Data for
adults (>=18-years) with a dermatology provider-given diagnosis of psoriasis from
9/2014-9/2015 were obtained from dermatology practices using a widely used US
dermatology-specific EHR containing over 500,000 psoriasis patients. Disease
severity was captured by static physician's global assessment and body surface
area. Patient-perceived treatment effectiveness was assessed by a pre-defined
question. Treatment switching and duration were documented. Reasons for
discontinuations were assessed using pre-defined selections. Healthcare resource
utilization was defined by visit frequency and complexity. RESULTS: From 82,621
patients with psoriasis during the study period, patient-perceived treatment
effectiveness was investigated in 2200 patients. The proportion of patients
reporting "strongly agree" when asked if their treatment was effective was
highest for biologics (73%) and those reporting treatment adherence (55%). In
16,000 patients who received oral systemics and 21,087 patients who received
biologics, median treatment duration was longer for those who received biologics
(160 vs. 113 days, respectively). Treatment switching was less frequent among
patients on systemic monotherapies compared to those on combination therapies.
The most common reason for discontinuing biologics was loss of efficacy; the most
common reason for discontinuing orals was side effects. In 28,754 patients,
higher disease severity was associated with increased healthcare resource
utilization (increased visit frequency and complexity). When compared between
treatment groups (n = 10,454), healthcare resource utilization was highest for
phototherapy. Annual medication costs were higher for biologics ($21,977) than
oral systemics ($3413). CONCLUSIONS: Real-world research using a widely
implemented dermatology EHR provided valuable insights on patient perceived
treatment effectiveness, patterns of medication usage, healthcare resource
utilization, and medication costs for psoriasis patients in the US. This study
and others utilizing EHRs for real-world research may assist clinical and payer
decisions regarding the management of psoriasis.
PMID- 29954364
TI - The impact of FSH receptor polymorphism on time-to-pregnancy: a cross-sectional
single-centre study.
AB - BACKGROUND: Single nucleotide polymorphism of the follicle-stimulating hormone
(FSH) receptor (FSHR) is an important marker of ovarian function. However, its
role in female fecundity remains debatable. The aim of the study to assess the
relationship of FSHR polymorphism of Serine/Serine, Asparagine/Asparagine and
Asparagine/Serine variants directly against the time-to-pregnancy (TTP) in women.
METHODS: Data were collected from 291 consecutive selected post-partum Caucasians
using this criterion: ethnicity, age between 21 and 34-year-old new mothers and,
0-3 days after delivery of newborns in the Klaipeda University Hospital,
Lithuania. Questionnaires on factors associated with conception were given to
patients, and blood samples were collected for genomic DNA extractions as well as
for analysis of follicle-stimulating hormone receptor gene polymorphism. Odds
ratios (OR) and 95% confidence intervals (CI) for time-to-pregnancy were
estimated by multivariate logistic regression. Women with unplanned pregnancies
and those who received assisted reproductive technologies were not included in
the study. RESULTS: After adjustment for other possible factors, increased risk
for time-to-pregnancy of 12 or more months was associated with: Serine/Serine
polymorphism variant (OR = 1.38, 95% CI 1.56-2.71, p = 0.007), age of 30 or more
years (OR = 1.95, 95% CI 1.25-2.71, p = 0.015), gynaecological diseases in the
past (OR = 2.21, 95% CI 1.12-5.74, p = 0.027), prior contraception use (OR =
1.87, 95% CI 1.14-3.64, p = 0.016), and fertility problems in the past (OR =
1.57, 95% CI 1.16-4.76, p = 0.019). CONCLUSION: The results suggest a possible
relationship of FSH receptor gene Serine/Serine variant for the lower possibility
of conception during the first 12 months of planned conception.
PMID- 29954365
TI - Care-physical activity initiatives in the neighbourhood: study protocol for mixed
methods research on participation, effective elements, impact, and funding
methods.
AB - BACKGROUND: In the Netherlands, people with a low socioeconomic status (SES) live
approximately 6 years less and are less engaged in physical activity (PA) than
high SES citizens. This contributes to the persistent health inequalities between
low and high SES citizens. Care-PA initiatives are deemed effective for
stimulating PA and improving health and participation among peoples with a low
SES. In those initiatives, multiple sectors (e.g. sports, health insurers,
municipalities) collaborate to connect primary care and PA at neighbourhood
level. This study focuses on two Dutch municipalities that aim to invest in
Health in All Policies (HiAP) and care-PA initiatives to improve the health of
people with low SES. The aim is to gain insight into (1) the short-term (3
months) and long-term (1 year) outcomes of participating in care-PA initiatives
for low SES citizens in terms of health, quality of life, and societal
participation, (2) the effective elements that contribute to these outcomes, (3)
the direct and perceived societal costs and benefits of care-PA initiatives, and
(4) alternative ways to fund integrated care, prevention, and care-PA initiatives
at neighbourhood level. METHODS: The study will be built on a mixed-methods
design guided by action research to continuously facilitate participatory
processes and practical solutions. To assess outcomes, body measurements and
questionnaires will be used as part of a pre-test/post-test design. Focus groups
and interviews will be conducted to gain an in-depth understanding of outcomes
and action elements. Action elements will be explored by using multiple tools:
concept mapping, the logic model, and capacity mapping. Direct and perceived
societal costs will be measured by administrative data from healthcare insurers
(before-after design) and the effectiveness arena. An alternative funding model
will be identified based on literature study, expert meetings, and municipal
workshops. DISCUSSION: Initiatives addressing multiple factors at different
levels in an integral way are a challenge for evaluation. Multi-methods and tools
are required, and data need to be interpreted comprehensively in order to
contribute to a contextual insight into what works and why in relation to HiAP
and care-PA initiatives.
PMID- 29954366
TI - Subjective well-being, drug attitude, and changes in symptomatology in chronic
schizophrenia patients starting treatment with new-generation antipsychotic
medication.
AB - BACKGROUND: Non-adherence to medication remains a major challenge in the long
term management of patients with schizophrenia. Next to lack of insight into the
illness, adverse effects of antipsychotic drugs, cognitive deficits, poor
therapeutic alliance, reduced quality of life, missing social support, and
negative attitudes toward medication are predictors of non-adherence. This study
examined potential correlations between attitudes toward antipsychotic drug
therapy, subjective well-being, and symptom change in patients with chronic
schizophrenia. METHODS: 30 patients with schizophrenia starting monotherapy with
a new-generation antipsychotic were included into the study. The Drug Attitude
Inventory (DAI) and the Subjective Well-being under Neuroleptic Treatment Scale,
short form (SWN-K), were administered after 2, 4, and 12 weeks of treatment. At
the same points in time and at baseline, psychopathological symptoms were rated
by means of the Positive and Negative Syndrome Scale (PANSS), and functioning was
assessed by means of the Global Assessment of Functioning Scale (GAF).
Antipsychotic induced side effects were evaluated by using the Udvalg for
Kliniske Undersogelser (UKU) Side Effect Rating Scale. RESULTS: Study
participants had a mean age of 37.5 +/- 9.7 years, baseline symptoms were mild.
The PANSS total score improved significantly from baseline to weeks 4 (p = .003)
and 12 (p = .001), respectively. Neither the DAI total score nor the SWN-K total
score changed significantly over the course of time. The severity of symptoms was
not correlated with drug attitude at any time point but was negatively correlated
with wellbeing at weeks 2 (r = -.419, p = .021) and 4 (r = -.441, p = .015).
There was no significant correlation between DAI and SWN-K total scores at any
time point. CONCLUSIONS: Next to showing that the DAI and the SWN-K measure
different aspects of subjective experiences during antipsychotic treatment these
findings emphasize the use of both instruments to optimize adherence to
medication.
PMID- 29954367
TI - Effectiveness of a diabetes prevention program for rural women with prior
gestational diabetes mellitus: study protocol of a multi-site randomized clinical
trial.
AB - BACKGROUND: In China, about 53.4 million women (11%) have type 2 diabetes (T2DM).
Women with prior 2 (GDM) are at a high risk for T2DM. Postpartum lifestyle
interventions have been effective in reducing T2DM for this population, but the
evidence is limited to interventions provided in urban areas, despite the fact
that a higher prevalence of undiagnosed T2DM was found in rural areas in China.
The primary purpose of this proposed study is to examine the effect of a
postpartum intensive lifestyle modification (ILSM) program on physiological
health outcomes (T2DM development, insulin resistance, and weight-related
variables), weight-related health behaviors (dietary intake and physical
activity), and psychosocial outcomes (self-efficacy, perceived stress, social
support, and health-related quality of life) compared to usual care at 3, 6, and
18 months post baseline assessment. The secondary outcomes are to identify
potential mediators and moderators on change of physiological health outcomes.
METHODS/DESIGN: A multi-site randomized clinical trial (RCT) will be conducted to
examine the efficacy of an evidence-based Intensive Lifestyle Modification (ILSM)
program compared with usual care for women with prior GDM living in rural areas
in China. A total sample of 256 participants will be recruited in the study. The
intervention consists of six bi-weekly in-person group sessions, five bi-weekly
telephone consultation sessions, and three monthly telephone consultations to
encourage behavior change. The usual care provided to the control group will
utilize current clinical guideline and recommendations for T2DM prevention.
Outcome measures include physiological variables (OGTT-2 h, HbA1c, weight, and
waist circumference); weight-related health behavioral (dietary intake and
physical activities); and psychosocial variables (self-efficacy and social
support) at 3-, 6- and 18- month after baseline. We will also assess the
potential cost-effectiveness of ILSM (net cost per T2DM case and per DALY
averted) compared with usual care. DISCUSSION: If successful, this ILSM program
can be adapted and used in rural areas as a blueprint for clinical guidelines to
decrease T2DM by improving postpartum GDM care in China. Findings of this study
are expected to make a significant contribution to public health practice and
health policy related to T2DM prevention in China. TRIAL REGISTRATION: Chinese
Clinical Trial Registry, ChiCTR1800015023 . Registered 1 March 2018 -
Retrospectively registered, http://apps.who.int/trialsearch/default.aspx .
PMID- 29954368
TI - Comprehensive transcriptomic analysis of heat shock proteins in the molecular
subtypes of human breast cancer.
AB - BACKGROUND: Heat Shock Proteins (HSPs), a family of genes with key roles in
proteostasis, have been extensively associated with cancer behaviour. However,
the HSP family is quite large and many of its members have not been investigated
in breast cancer (BRCA), particularly in relation with the current molecular BRCA
classification. In this work, we performed a comprehensive transcriptomic study
of the HSP gene family in BRCA patients from both The Cancer Genome Atlas (TCGA)
and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC)
cohorts discriminating the BRCA intrinsic molecular subtypes. METHODS: We
examined gene expression levels of 1097 BRCA tissue samples retrieved from TCGA
and 1981 samples of METABRIC, focusing mainly on the HSP family (95 genes). Data
were stratified according to the PAM50 gene expression (Luminal A, Luminal B,
HER2, Basal, and Normal-like). Transcriptomic analyses include several
statistical approaches: differential gene expression, hierarchical clustering and
survival analysis. RESULTS: Of the 20,531 analysed genes we found that in BRCA
almost 30% presented deregulated expression (19% upregulated and 10%
downregulated), while of the HSP family 25% appeared deregulated (14% upregulated
and 11% downregulated) (|fold change| > 2 comparing BRCA with normal breast
tissues). The study revealed the existence of shared HSP genes deregulated in all
subtypes of BRCA while other HSPs were deregulated in specific subtypes. Many
members of the Chaperonin subfamily were found upregulated while three members
(BBS10, BBS12 and CCTB6) were found downregulated. HSPC subfamily had moderate
increments of transcripts levels. Various genes of the HSP70 subfamily were
upregulated; meanwhile, HSPA12A and HSPA12B appeared strongly downregulated. The
strongest downregulation was observed in several HSPB members except for HSPB1.
DNAJ members showed heterogeneous expression pattern. We found that 23 HSP genes
correlated with overall survival and three HSP-based transcriptional profiles
with impact on disease outcome were recognized. CONCLUSIONS: We identified shared
and specific HSP genes deregulated in BRCA subtypes. This study allowed the
recognition of HSP genes not previously associated with BRCA and/or any cancer
type, and the identification of three clinically relevant clusters based on HSPs
expression patterns with influence on overall survival.
PMID- 29954369
TI - Long-term efficacy of lenvatinib for recurrent papillary thyroid carcinoma after
multimodal treatment and management of complications: a case report.
AB - BACKGROUND: The advent of tyrosine kinase inhibitors (TKIs) has changed the
treatment of RAI refractory, unresectable recurrent differentiated thyroid cancer
(DTC), which was formerly treated with multidisciplinary remedies. CASE
PRESENTATION: Here we describe the case of a 64-year-old woman who underwent
total thyroidectomy with tracheal resection and suffered from a recurrent tumor
in the neck and multiple lung and bone metastases 3 and 11 months, respectively,
after the operation. Multimodal therapies, RI (I-131), EBRT, and taxane-based
chemotherapy were ineffective, and sorafenib was started as a TKI. However,
because of disease progression, sorafenib was replaced by lenvatinib after 9
months. The effect of lenvatinib has continued for more than 1 year and 9 months,
and the patient has well survived. During the treatment period, a tracheal pin
hole fistula suddenly emerged, which was naturally cured by the temporary
cessation of lenvatinib. Adverse events such as hypertension, proteinuria, and
diabetes as innate complications have been successfully managed until the present
according to our institute regulations. CONCLUSIONS: Even where multimodal
treatment was ineffective, lenvatinib was suggested to be an alternative
treatment option for RAI refractory recurrent DTC and patient could have a chance
to be controlled successfully.
PMID- 29954370
TI - A postpartum vaccination promotion intervention using motivational interviewing
techniques improves short-term vaccine coverage: PromoVac study.
AB - BACKGROUND: Due to the increasing number of vaccine-hesitant parents, new
effective immunization promotion strategies need to be developed to improve the
vaccine coverage (VC) of infants. This study aimed to assess the impact of an
educational strategy of vaccination promotion based on motivational interviewing
(MI) techniques targeting parents and delivered at the maternity ward, for the VC
of infants at 3, 5, and 7 months of age. METHODS: An individual educational
information session, administered using MI techniques, regarding immunization of
infants aged 2, 4, and 6 months was (experimental group) or was not (control
group) proposed to parents during the postpartum stay at the maternity ward.
Immunization data were obtained through the Eastern Townships Public Health
registry for infants at 3, 5, and 7 months of age. Absolute VC increases at 3, 5,
and 7 months in the experimental group were calculated and the relative risks
with the respective 95% confidence intervals were computed using univariate
logistic regression with the generalized estimating equations (GEE) procedure.
Multivariate regression using GEE was used to adjust for confounding variables.
RESULTS: In the experimental and control groups, 1140 and 1249 newborns were
included, respectively. A significant increase in VC of 3.2, 4.9, and 7.3% was
observed at 3, 5, and 7 months of age (P < 0.05), respectively. The adjusted
relative risk of the intervention's impact on vaccination status at 7 months of
age was 1.08 (95% confidence interval: 1.03-1.14) (P = 0.002). CONCLUSIONS: An
educational strategy using MI techniques delivered at the maternity ward may be
effective in increasing VC of infants at ages 3, 5, and 7 months. MI could be an
effective tool to overcome vaccine hesitancy.
PMID- 29954371
TI - The role of severity perceptions and beliefs in natural infections in Shanghai
parents' vaccine decision-making: a qualitative study.
AB - BACKGROUND: China has reduced incidence of vaccine-preventable diseases through
its Expanded Program on Immunization (EPI). Vaccines outside of the EPI are not
provided for free by the government, however. This study explored how the stated
importance of different disease and vaccine-related attributes interacted with
beliefs about the immune system of a child to affect Chinese parents' decision to
obtain a non-EPI vaccine. METHODS: Mothers and fathers of young children at
immunization clinics in Shanghai, China, were interviewed about vaccine decision
making and what attributes of a disease were important when making this decision.
An inductive thematic analysis explored their beliefs about disease attributes
and how these related to vaccination decisions. RESULTS: Among the 34 interviews,
severity of the disease-particularly in causing long-term disability-was the most
commonly cited factor influencing a parent's decision to get a vaccine for their
child. Many parents believed that natural infection was preferable to
vaccination, as long as disease was not severe, and many were concerned that
imported vaccines were inadequate for Chinese children's physical constitutions.
All these beliefs could influence the decision to vaccinate. CONCLUSIONS: Many
parents do not appear to understand how and why vaccines can support development
of a healthy immune system. Because severity emerged as parents' overriding
concern when making decisions about vaccines, marketing for a childhood vaccine
could focus on the severe condition that a vaccine can protect against.
PMID- 29954372
TI - Development and evaluating multimarker models for guiding treatment decisions.
AB - BACKGROUND: Despite the growing interest in developing markers for predicting
treatment response and optimizing treatment decisions, an appropriate methodology
to identify, combine and evaluate such markers has been slow to develop. We
propose a step-by-step strategy for analysing data from existing randomised
trials with the aim of identifying a multi-marker model for guiding decisions
about treatment. METHODS: We start with formulating the treatment selection
problem, continue with defining the treatment threshold, prepare a list of
candidate markers, develop the model, apply the model to estimate individual
treatment effects, and evaluate model performance in the study group of patients
who meet the trial eligibility criteria. In this process, we rely on some well
known techniques for multivariable prediction modelling, but focus on predicting
benefit from treatment, rather than outcome itself. We present our approach using
data from a randomised trial in which 808 women with multiple pregnancy were
assigned to cervical pessary or control, to prevent adverse perinatal outcomes.
Overall, cervical pessary did not reduce the risk of adverse perinatal outcomes.
RESULTS: The treatment threshold was zero. We had a preselected list of 5
potential markers and developed a logistic model including the markers, treatment
and all marker-by-treatment interaction terms. The model was well calibrated and
identified 35% (95% confidence interval (CI) 32 to 39%) of the trial participants
as benefitting from pessary insertion. We estimated that the risk of adverse
outcome could be reduced from 13.5 to 8.1% (5.4% risk reduction; 95% CI 2.1 to
8.6%) through model-based selective pessary insertion. The next step is external
validation upon existence of independent trial data. CONCLUSIONS: We suggest
revisiting existing trials data to explore whether differences in treatment
benefit can be explained by differences in baseline characteristics of patients.
This could lead to treatment selection tools which, after validation in
comparable existing trials, can be introduced into clinical practice for guiding
treatment decisions in future patients.
PMID- 29954373
TI - Best practice framework for Patient and Public Involvement (PPI) in collaborative
data analysis of qualitative mental health research: methodology development and
refinement.
AB - BACKGROUND: Patient and Public Involvement (PPI) in mental health research is
increasing, especially in early (pre-funding) stages. PPI is less consistent in
later stages, including in analysing qualitative data. The aims of this study
were to develop a methodology for involving PPI co-researchers in collaboratively
analysing qualitative mental health research data with academic researchers, to
pilot and refine this methodology, and to create a best practice framework for
collaborative data analysis (CDA) of qualitative mental health research. METHODS:
In the context of the RECOLLECT Study of Recovery Colleges, a critical literature
review of collaborative data analysis studies was conducted, to identify
approaches and recommendations for successful CDA. A CDA methodology was
developed and then piloted in RECOLLECT, followed by refinement and development
of a best practice framework. RESULTS: From 10 included publications, four CDA
approaches were identified: (1) consultation, (2) development, (3) application
and (4) development and application of coding framework. Four characteristics of
successful CDA were found: CDA process is co-produced; CDA process is realistic
regarding time and resources; demands of the CDA process are manageable for PPI
co-researchers; and group expectations and dynamics are effectively managed. A
four-meeting CDA process was piloted to co-produce a coding framework based on
qualitative data collected in RECOLLECT and to create a mental health service
user-defined change model relevant to Recovery Colleges. Formal and informal
feedback demonstrated active involvement. The CDA process involved an extra 80
person-days of time (40 from PPI co-researchers, 40 from academic researchers).
The process was refined into a best practice framework comprising Preparation,
CDA and Application phases. CONCLUSIONS: This study has developed a typology of
approaches to collaborative analysis of qualitative data in mental health
research, identified from available evidence the characteristics of successful
involvement, and developed, piloted and refined the first best practice framework
for collaborative analysis of qualitative data. This framework has the potential
to support meaningful PPI in data analysis in the context of qualitative mental
health research studies, a previously neglected yet central part of the research
cycle.
PMID- 29954374
TI - A 12-week evaluation of annatto tocotrienol supplementation for postmenopausal
women: safety, quality of life, body composition, physical activity, and nutrient
intake.
AB - BACKGROUND: Evidence suggests that tocotrienols may benefit bone health in
osteopenic women. However, their safety in this population has never been
investigated. This study was to evaluate the safety of a 12-week supplementation
of annato tocotrienol in postmenopausal osteopenic women, along with effects of
the supplementation on quality of life, body composition, physical activity, and
nutrient intake in this population. METHODS: Eighty nine postmenopausal
osteopenic women were randomly assigned to 3 treatment arms: (1) Placebo (430 mg
olive oil/day), (2) Low tocotrientol (Low TT) (430 mg tocotrienol/day from
DeltaGold 70 containing 300 mg tocotrienol) and (3) High tocotrienol (High TT)
(860 mg tocotrienol/day from DeltaGold 70 containing 600 mg tocotrienol) for 12
weeks. DeltaGold 70 is an extract from annatto seed with 70% tocotrienol
consisting of 90% delta-tocotrienol and 10% gamma-tocotrienol. Safety was
examined by assessing liver enzymes (aspartate aminotransferase, alanine
aminotransferase), alkaline phosphatase, bilirubin, kidney function (blood urea
nitrogen and creatinine), electrolytes, glucose, protein, albumin, and globulin
at 0, 6, and 12 weeks. Serum tocotrienol and tocopherol concentrations were
assessed and pills counted at 0, 6, and 12 weeks. Quality of life, body
composition, physical activity, and dietary macro- and micro-nutrient intake were
evaluated at 0 and 12 weeks. A mixed model of repeated measures ANOVA was applied
for analysis. RESULTS: Eighty seven subjects completed the study. Tocotrienol
supplementation did not affect liver or kidney function parameters throughout the
study. No adverse event due to treatments was reported by the participants.
Tocotrienol supplementation for 6 weeks significantly increased serum delta
tocotrienol level and this high concentration was sustained to the end of study.
There was no difference in serum delta-tocotrienol levels between the Low TT and
the High TT groups. No effects of tocotrienol supplementation were observed on
quality of life, body composition, physical activity, and nutrient intake.
CONCLUSIONS: Annatto-derived tocotrienol up to 600 mg per day for 12 weeks
appeared to be safe in postmenopausal osteopenic women, particularly in terms of
liver and kidney functions. Tocotrienol supplementation for 12 weeks did not
affect body composition, physical activity, quality of life, or intake of macro-
and micro-nutrients in these subjects. TRIAL REGISTRATION: ClinicalTrials.gov
identifier: NCT02058420 . TITLE: Tocotrienols and bone health of postmenopausal
women.
PMID- 29954375
TI - Preoperative controlling nutritional status (CONUT) score as a predictor of long
term outcome after curative resection followed by adjuvant chemotherapy in stage
II-III gastric Cancer.
AB - BACKGROUND: The prognostic value of preoperative controlling nutritional status
(CONUT) has been reported in many malignancies. In present study, we aimed to
clarify the prognostic impact of CONUT in gastric cancer (GC) receiving curative
resection and adjuvant chemotherapy. METHODS: We retrospectively reviewed 697
consecutive patients undergoing curative surgery followed by adjuvant
chemotherapy for Stage II-III GC between November 2000 and September 2012.
Patients were classified into high (>=3) and low (<=2) CONUT groups according to
the receiver operating characteristic (ROC) analysis. RESULTS: Of the included
patients, 217 (31.1%) belonged to the high CONUT group. The high CONUT group had
a significantly lower 5-year cancer-specific survival (CSS) rate than the low
CONUT group (39.3 vs. 55.5%, P < 0.001). High CONUT score was significantly
associated with larger tumor size, more lymph node metastasis, and poorer
nutritional status, including lower body mass index (BMI), higher prognostic
nutritional index (PNI) and the presence of preoperative anemia (all P < 0.05).
Multivariate analysis revealed that CONUT score was an independent prognostic
factor (HR: 1.553; 95% CI: 1.080-2.232; P = 0.017). Of note, in the low PNI
group, CONUT score still effectively stratified CSS (P = 0.016). Furthermore, the
prognostic significance of CONUT score was also maintained when stratified by TNM
stage (all P < 0.05). CONCLUSIONS: CONUT score is considered a useful nutritional
marker for predicting prognosis in stage II-III GC patients undergoing curative
resection and adjuvant chemotherapy, and may help to facilitate the planning of
preoperative nutritional interventions.
PMID- 29954376
TI - The effects of graduate competency-based education and mastery learning on
patient care and return on investment: a narrative review of basic anesthetic
procedures.
AB - BACKGROUND: Despite the widespread implementation of competency-based education,
evidence of ensuing enhanced patient care and cost-benefit remains scarce. This
narrative review uses the Kirkpatrick/Phillips model to investigate the patient
related and organizational effects of graduate competency-based medical education
for five basic anesthetic procedures. METHODS: The MEDLINE, ERIC, CINAHL, and
Embase databases were searched for papers reporting results in
Kirkpatrick/Phillips levels 3-5 from graduate competency-based education for five
basic anesthetic procedures. A gray literature search was conducted by reference
search in Google Scholar. RESULTS: In all, 38 studies were included,
predominantly concerning central venous catheterization. Three studies reported
significant cost-effectiveness by reducing infection rates for central venous
catheterization. Furthermore, the procedural competency, retention of skills and
patient care as evaluated by fewer complications improved in 20 of the reported
studies. CONCLUSION: Evidence suggests that competency-based education with
procedural central venous catheterization courses have positive effects on
patient care and are both cost-effective. However, more rigorously controlled and
reproducible studies are needed. Specifically, future studies could focus on
organizational effects and the possibility of transferability to other medical
specialties and the broader healthcare system.
PMID- 29954377
TI - The impact of psychotic experiences in the early stages of mental health problems
in young people.
AB - BACKGROUND: Anxiety and depressive symptoms and psychotic experiences constitute
common features of emerging mental disorders in young people. Psychotic
experiences and the ultra-high risk (UHR) state for psychosis appear to have a
particular importance for clinical presentation, progression of symptomatology,
quality of life and functioning, but the impact of psychotic experiences in
individuals seeking help at non-UHR services, compared to UHR services, is under
researched. METHODS: Sixty-nine young people (Mage +/- SD at baseline = 20.8 +/-
2.6, range 16-26 years, 48 females) presenting to mental health services were
grouped according to UHR and non-UHR status. They were assessed at baseline for
anxiety and depressive symptoms, psychological distress, psychosocial functioning
and quality of life. They were followed up at three, six, and 12 months. Data
were analysed using mixed linear modelling. RESULTS: UHR individuals reported
higher levels of depressive symptoms and psychological distress, and lower levels
of role functioning and quality of life compared to non-UHR individuals. No
differences were reported for anxiety symptoms or social functioning. Decline in
psychosocial functioning was not associated with clinical deterioration or
reduction of quality of life. CONCLUSIONS: Psychotic experiences appear to be
particularly associated with depressive symptoms and psychological distress,
impaired role functioning and quality of life in help-seeking young people in the
medium-term. It is therefore important to pay special attention to psychotic
experiences in the early stages of mental health problems even if psychotic
symptoms are not the main motivation for help-seeking.
PMID- 29954378
TI - A computational application for multi-skill nurse staffing in hospital units.
AB - BACKGROUND: Approaches to nurse staffing are commonly concerned with determining
the minimum number of care hours according to the illness severity of patients.
However, there is a gap in the literature considering multi-skill and multi-shift
nurse staffing. This study addresses nurse staffing per skill category, at a
strategical decision level, by considering the organization of work in shifts and
coping with variability in demand. METHODS: We developed a method to determine
the nursing staff levels in a hospital, given the required patient assistance.
This method relies on a new mathematical model for complying with the legislation
and guidelines while minimizing salary costs. A spreadsheet-based tool was
developed to embed the model and to allow simulating different scenarios and
evaluating the impact of demand fluctuations, thus supporting decision-making on
staff dimensioning. RESULTS: Experiments were carried out considering real data
from a Brazilian hospital unit. The results obtained by the model support the
current total staff level in the unit under study. However, the distribution of
staff among different skill categories revealed that the current real situation
can be improved. CONCLUSIONS: The method allows the determining of staff level
per shift and skill depending on the mix of patients' illness severity. Hospital
management is offered the possibility of optimizing the staff level using a
spreadsheet, a tool most managers are familiar with. In addition, it is possible
to evaluate the implications of decisions on workforce dimensioning by simulating
different demand scenarios. This tool can be easily adapted to other hospitals,
using local rules and legislation.
PMID- 29954379
TI - Management of financial conflicts of interests in clinical practice guidelines in
Germany: results from the public database GuidelineWatch.
AB - BACKGROUND: The reliability of clinical practice guidelines has been disputed
because guideline panel members are often burdened with financial conflicts of
interest (COI). Current recommendations for COI regulation advise not only
detailed declaration but also active management of conflicts. To continuously
assess COI declaration and management in German guidelines we established the
public database LeitlinienWatch (GuidelineWatch). METHODS: We analyzed all German
guidelines at the highest methodological level (S3) that included recommendations
for pharmacological therapy (n = 67) according to five criteria: declaration and
assessment of COI, composition of the guideline development group, independence
of the coordinators and lead authors, imposed abstentions because of COI and
public external review. Each criterion was assessed using predefined outcome
categories. RESULTS: Most guidelines (76%) contained a detailed declaration of
COI. However, none of the guidelines provided full transparency of COI assessment
results. The guideline group was composed of a majority of participants with COI
in 55% of the guidelines, no guideline was free of participants with COI. Only 9%
of guidelines had coordinators and lead authors without any financial COI. Most
guidelines (70%) did not provide a rule for abstentions for participants with
COI. In 21% of guidelines there was a rule, but abstentions were either not
practiced or not documented, whereas in 7% partial abstentions and in 2% complete
abstentions were documented. Two thirds of the guideline drafts (67%) were not
externally reviewed via a public website. CONCLUSIONS: COI are usually documented
in detail in German guidelines of the highest methodological level. However,
considerable improvement is needed regarding active management of COI, including
recruitment of independent experts for guideline projects, abstention from voting
for participants with COI and external review of the guideline draft. We assume
that the publicly available ratings on GuidelineWatch will improve the handling
of conflicts of interest in guideline development.
PMID- 29954380
TI - Efficacy and safety of the artificial pancreas in the paediatric population with
type 1 diabetes.
AB - BACKGROUND: Type 1 diabetes (DM1) is one of the most common chronic diseases in
childhood and requires life-long insulin therapy and continuous health care
support. An artificial pancreas (AP) or closed-loop system (CLS) have been
developed with the aim of improving metabolic control without increasing the risk
of hypoglycaemia in patients with DM1. As the impact of APs have been studied
mainly in adults, the aim of this review is to evaluate the efficacy and safety
of the AP in the paediatric population with DM1. MAIN BODY: The real advantage of
a CLS compared to last-generation sensor-augmented pumps is the gradual
modulation of basal insulin infusion in response to glycaemic variations (towards
both hyperglycaemia and hypoglycaemia), which has the aim of improving the
proportion of time spent in the target glucose range and reducing the mean
glucose level without increasing the risk of hypoglycaemia. Some recent studies
demonstrated that also in children and adolescents an AP is able to reduce the
frequency of hypoglycaemic events, an important limiting factor in reaching good
metabolic control, particularly overnight. However, the advantages of the AP in
reducing hyperglycaemia, increasing the time spent in the target glycaemic range
and thus reducing glycated haemoglobin are less clear and require more clinical
trials in the paediatric population, in particular in younger children.
CONCLUSIONS: Although the first results from bi-hormonal CLS are promising, long
term, head-to-head studies will have to prove their superiority over insulin-only
approaches. More technological progress, the availability of more fast-acting
insulin, further developments of algorithms that could improve glycaemic control
after meals and physical activity are the most important challenges in reaching
an optimal metabolic control with the use of the AP in children and adolescents.
PMID- 29954381
TI - Psychometric evaluation of the Persian version of the Lymphedema Life Impact
Scale (LLIS, version 1) in breast cancer patients.
AB - BACKGROUND: Despite the high prevalence of lymphedema in Iranian breast cancer
patients, there is no valid instrument for measuring quality of life in this
population. The aim of this study was to assess reliability and validity of the
Persian version of Lymphedema Life Impact Scale (LLIS) in breast cancer patients.
METHODS: Forward-backward procedure was applied to translate The LLIS from
English into Persian. The LLIS is an 18-item measure of physical, psychosocial,
and functional impairments caused by lymphedema. Experts and patients assessed
content and face validity, respectively. Discriminant validity was evaluated by
comparing breast cancer patients with and without lymphedema. Convergent validity
was assessed by comparing LLIS score with SF-36 (functional component) and the
EORTC-QLQ-C30 (functional component). The construct validity also was evaluated
using confirmatory and exploratory factor analyses. Internal consistency was
evaluated by Cronbach's alpha coefficient. Stability was assessed by test-retest
analysis over a one-week interval in 13 patients. RESULTS: In all 446 breast
cancer patients were entered into the study. The content and face validity of
Persian version of LLIS were acceptable and minor corrections were applied in
final version. The questionnaire differentiated well in patients' with and
without lymphedema and not lending support to its discriminant validity.
Confirmatory factor analysis showed a good fit for the data. Cronbach's alpha
coefficient in physical, psychosocial and functional subscales were 0.873, 0.854
and 0.884 respectively. Intra-class correlation coefficient of total score of the
LLIS was 0.96. CONCLUSIONS: The findings of this study suggest a first indication
that reliability and validity of the Persian version of LLIS in patients with
breast cancer induced lymphedema was good. Application of this instrument for
identifying problems of patients with upper extremity lymphedema may be helpful
in designing interventions to improve quality of life.
PMID- 29954382
TI - Establishing the HLS-Q12 short version of the European Health Literacy Survey
Questionnaire: latent trait analyses applying Rasch modelling and confirmatory
factor analysis.
AB - BACKGROUND: The European Health Literacy Survey Questionnaire (HLS-EU-Q47) is
widely used in assessing health literacy (HL). There has been some controversy
whether the comprehensive HLS-EU-Q47 data, reflecting a conceptual model of four
cognitive domains across three health domains (i.e. 12 subscales), fit
unidimensional Rasch models. Still, the HLS-EU-Q47 raw score is commonly
interpreted as a sufficient statistic. Combining Rasch modelling and confirmatory
factor analysis, we reduced the 47 item scale to a parsimonious 12 item scale
that meets the assumptions and requirements of objective measurement while
offering a clinically feasible HL screening tool. This paper aims at (1)
evaluating the psychometric properties of the HLS-EU-Q47 and associated short
versions in a large Norwegian sample, and (2) establishing a short version (HLS
Q12) with sufficient psychometric properties. METHODS: Using computer-assisted
telephone interviews during November 2014, data were collected from 900 randomly
sampled individuals aged 16 and over. The data were analysed using the partial
credit parameterization of the unidimensional polytomous Rasch model (PRM) and
the 'between-item' multidimensional PRM, and by using one-factorial and multi
factorial confirmatory factor analysis (CFA) with categorical variables. RESULTS:
Using likelihood-ratio tests to compare data-model fit for nested models, we
found that the observed HLS-EU-Q47 data were more likely under a 12-dimensional
Rasch model than under a three- or a one-dimensional Rasch model. Several of the
12 theoretically defined subscales suffered from low reliability owing to few
items. Excluding poorly discriminating items, items displaying differential item
functioning and redundant items violating the assumption of local independency, a
parsimonious 12-item HLS-Q12 scale is suggested. The HLS-Q12 displayed acceptable
fit to the unidimensional Rasch model and achieved acceptable goodness-of-fit
indexes using CFA. CONCLUSIONS: Unlike the HLS-EU-Q47 data, the parsimonious 12
item version (HLS-Q12) meets the assumptions and the requirements of objective
measurement while offering clinically feasible screening without applying
advanced psychometric methods on site. To avoid invalid measures of HL using the
HLS-EU-Q47, we suggest using the HLS-Q12. Valid measures are particularly
important in studies aiming to explain the variance in the latent trait HL, and
explore the relation between HL and health outcomes with the purpose of informing
policy makers.
PMID- 29954383
TI - Overweight modifies the association between long-term ambient air pollution and
prehypertension in Chinese adults: the 33 Communities Chinese Health Study.
AB - BACKGROUND: Research regarding the interaction of ambient air pollution and
overweight on prehypertension is scarce. We aimed to test whether overweight
modifies the association between long-term exposure to ambient air pollution and
prehypertension in Chinese adults. METHODS: A total of 16,188 Chinese adults,
aged 18-74 years old, from 33 communities in 3 Northeastern Chinese cities were
evaluated. Three-year average levels of particles with an aerodynamic diameter <=
10 MUm (PM10), sulfur dioxides (SO2), nitrogen dioxides (NO2), and ozone (O3)
were calculated at monitoring stations. Generalized additive models and 2-level
regression analyses were applied. RESULTS: We observed significant interactions
between air pollutants and overweight on prehypertension and blood pressure. The
associations of PM10, SO2, NO2, and O3 with prehypertension were significant
among overweight participants (Prevalence Rate Ratios (PRRs) per interquartile
range (IQR) of air pollutants: 1.14-1.20), but not among normal weight
participants (PRRs: 0.98-1.04). PM10, SO2, and O3 were significantly associated
with systolic blood pressure (SBP), and the magnitudes of these associations were
higher among overweight adults (increases in SBP per IQR of air pollutants: 1.82
4.53 mmHg) than those among normal weight adults (increases in SBP: 0.42-0.61
mmHg). For diastolic blood pressure (DBP), significant associations were mainly
observed in overweight participants (increases in DBP: 0.80-1.63 mmHg). Further
stratified analyses showed that all these interactions were stronger in women,
the older, and participants living in areas with lower income levels or higher
population density. CONCLUSIONS: Being overweight may enhance the effects of
ambient air pollution on prehypertension and blood pressure in Chinese adults.
PMID- 29954385
TI - Rapid guidelines - timely and important guidance needed for setting standards and
best practices.
PMID- 29954384
TI - Inter-rater agreement of the Quality of Life-Alzheimer's Disease (QoL-AD) self
rating and proxy rating scale: secondary analysis of RightTimePlaceCare data.
AB - BACKGROUND: To assess the quality of life of people with dementia, measures are
required for self-rating by the person with dementia, and for proxy rating by
others. The Quality of Life in Alzheimer's Disease scale (QoL-AD) is available in
two versions, QoL-AD-SR (self-rating) and QoL-AD-PR (proxy rating). The aim of
our study was to analyse the inter-rater agreement between self- and proxy
ratings, in terms of both the total score and the items, including an analysis
specific to care setting, and to identify factors associated with this agreement.
METHODS: Cross-sectional QoL-AD data from the 7th Framework European
RightTimePlaceCare study were analysed. A total of 1330 cases were included: n =
854 receiving home care and n = 476 receiving institutional long-term nursing
care. The proxy raters were informal carers (home care) and best-informed
professional carers (institutional long-term nursing care). Inter-rater agreement
was investigated using Bland-Altman plots for the QoL-AD total score and by
weighted kappa statistics for single items. Associations were investigated by
regression analysis. RESULTS: The overall QoL-AD assessment of those with
dementia revealed a mean value of 33.2 points, and the proxy ratings revealed a
mean value of 29.8 points. The Bland-Altman plots revealed a poor agreement
between self- and proxy ratings for the overall sample and for both care
settings. With one exception (item 'Marriage' weighted kappa 0.26), the weighted
kappa values for the single QoL-AD items were below 0.20, indicating poor
agreement. Home care setting, dementia-related behavioural and psychological
symptoms, and the functional status of the person with dementia, along with the
caregiver burden, were associated with the level of agreement. Only the home care
setting was associated with an increase larger than the predefined acceptable
difference between self- and proxy ratings. CONCLUSIONS: Proxy quality of life
ratings from professional and informal carers appear to be lower than the self
ratings of those with dementia. QoL-AD-SR and QoL-AD-PR are therefore not
interchangeable, as the inter-rater agreement differs distinctly. Thus, a proxy
rating should be judged as a complementary perspective for a self-assessment of
quality of life by those with dementia, rather than as a valid substitute.
PMID- 29954387
TI - International conference on Cell Death in Cancer and Toxicology 2018 (CDCT-2018).
AB - The International Conference on Cell Death in Cancer and Toxicology 2018
(February 20-22, 2018) provided an international forum for scientific
collaborations across multiple disciplines in cancer, cell death, and toxicology.
During the three-day symposium, researchers and clinicians shared recent advances
in basic, clinical, and translational research in cancer. Several student poster
abstracts were selected for platform talks and many young investigators
participated in the meeting. Together, this highly interactive meeting showcased
the rapid expansion in biomedical research in India and paved the way for future
meetings on cell death and cancer throughout India.
PMID- 29954386
TI - In renal cell carcinoma the PTEN splice variant PTEN-Delta shows similar function
as the tumor suppressor PTEN itself.
AB - BACKGROUND: Loss of PTEN is involved in tumor progression of several tumor
entities including renal cell carcinoma (RCC). During the translation process
PTEN generates a number of splice variants, including PTEN-Delta. We analyzed the
impact of PTEN-Delta in RCC progression. METHODS: In specimens of RCC patients
the expression of PTEN-Delta and PTEN was quantified. The PTEN expressing RCC
cell line A498 and the PTEN deficient 786-O cell line were stably transfected
with the PTEN-Delta or PTEN transcript. In Caki-1 cells that highly express PTEN
Delta, this isoform was knocked down by siRNA. Cell migration, adhesion,
apoptosis and signaling pathways activities were consequently analyzed in vitro.
RESULTS: Patients with a higher PTEN-Delta expression had a longer lymph node
metastasis free and overall survival. In RCC specimens, the PTEN-Delta expression
correlated with the PTEN expression. PTEN-Delta as well as PTEN induced a reduced
migration when using extracellular matrix (ECM) compounds as chemotaxins. This
effect was confirmed by knockdown of PTEN-Delta, inducing an enhanced migration.
Likewise a decreased adhesion on these ECM components could be shown in PTEN
Delta and PTEN transfected cells. The apoptosis rate was slightly increased by
PTEN-Delta. In a phospho-kinase array and Western blot analyses a consequently
reduced activity of AKT, p38 and JNK could be shown. CONCLUSIONS: We could show
that the PTEN splice variant PTEN-Delta acts similar to PTEN in a tumor
suppressive manner, suggesting synergistic effects of the two isoforms. The
impact of PTEN-Delta in context of tumor progression should thus be taken into
account when generating new therapeutic options targeting PTEN signaling in RCC.
PMID- 29954388
TI - Development and validation of a model for the adoption of structured and
standardised data recording among healthcare professionals.
AB - BACKGROUND: Healthcare professionals provide care to patients and during that
process, record large quantities of data in patient records. Data in an
Electronic Health Record should ideally be recorded once and be reusable within
the care process as well as for secondary purposes. A common approach to realise
this is to let healthcare providers record data in a standardised and structured
way at the point of care. Currently, it is not clear to what extent this
structured and standardised recording has been adopted by healthcare
professionals and what barriers to their adoption exist. Therefore, we developed
and validated a multivariable model to capture the concepts underlying the
adoption of structured and standardised recording among healthcare professionals.
METHODS: Based on separate models from the literature we developed a new
theoretical model describing the underlying concepts of the adoption of
structured and standardised recording. Using a questionnaire built upon this
model we gathered data to perform a summative validation of our model. Validation
was done through partial least squares structural equation modelling (PLS-SEM).
The quality of both levels defined in PLS-SEM analysis, i.e., the measurement
model and the structural model, were assessed on performance measures defined in
literature. RESULTS: The theoretical model we developed consists of 29 concepts
related to information systems as well as organisational factors and personal
beliefs. Based on these concepts, 59 statements with a 5 point Likert-scale
(fully disagree to fully agree) were specified in the questionnaire. We received
3584 responses. The validation shows our model is supported to a large extent by
the questionnaire data. Intention to record in a structured and standardised way
emerged as a significant factor of reported behaviour (beta = 0.305, p < 0.001).
This intention is influenced most by attitude (beta = 0.512, p < 0.001).
CONCLUSIONS: This model can be used to measure the perceived level of adoption of
structured and standardised recording among healthcare professionals and further
improve knowledge on the barriers and facilitators of this adoption.
PMID- 29954389
TI - The burden of war-injury in the Palestinian health care sector in Gaza Strip.
AB - BACKGROUND: War-related injury is a major public health concern, and a leading
cause of mortality, morbidity, and disability globally, particularly in low and
middle-income countries such as Palestine. Little is known about the burden of
war-related injury in the Palestinian context. The objective of this study was to
characterize the incidence and pattern of injuries, associated with war in Gaza
Strip, from July 8 to August 26, 2014. METHODS: This was a descriptive study
based on an injury registry at hospital facilities in the Gaza Strip. A total of
420 victims records from 2014 Gaza war injuries were randomly selected,
proportionate to the size of the study population estimated across five Gaza
governorates. Simple descriptive statistics were calculated to explore the
frequency and percentage distribution of study variables and injury data. A chi
square test (X2) was used. The significance level was derived at p < 0.05. The
data were analyzed by IBM SPSS software, version 23. RESULTS: Males (75.5%) have
experienced more war-related injuries than females (24.5%), constituting a male:
female ratio of 3.1:1. Almost half (49.5%) of the injured victims were of the age
group 20-39, followed by children and adolescents (< 20 years), accounting for
31.4%. More than half of victims were single (53.6%), 44.3% were married and the
rest were widowed or divorced. The overall number of injuries was 6.4 per 1000
population, though it varied among regions. North Gaza reported the highest
number of injuries (9.0) and Rafah the lowest (4.7) per 1000 population. Blast
and explosion were found to be the most common causes of war injuries (72.9%).
The highest proportion of injuries were reported in the upper body. Multiple body
shrapnel wounds and burns (39.3%) were most frequent. Other types of injuries
were multiple organ injury (24.3%), fractures (13.6%), internal organ injury and
bleeding (9.8%), amputation (4.5%), abrasions/lacerations and contusions (4.8%),
vision or hearing loss or both (1.9%) and respiratory problems (1.9%). The
highest percentage of injuries were classified as mild (46.9%), and the rest
ranged from moderate-to-severe. Almost 26% of individuals had sustained
disability, and most of them had physical/motor impairment. CONCLUSION: War
related injuries constitute a major problem to public health discipline and
clinical medicine as well. A better surveillance system using ICD codes, and
development of a comprehensive electronic data network are necessary to make
future research easier and more timely.
PMID- 29954390
TI - Management of intrahepatic splenosis:a case report and review of the literature.
AB - BACKGROUND: Splenosis is the heterotopic autotransplantation and implantation of
splenic tissue after splenic trauma or splenectomy. Considering that splenosis
often occurs in the mesentery, omentum, and peritoneum, intrahepatic splenosis
has seldom been reported. We report a rare case of isolated intrahepatic
splenosis in a 54-year-old man who presented with a liver mass thought to be
hepatocellular carcinoma. CASE PRESENTATION: A 54-year-old man was referred to
our hospital for further evaluation of a liver lesion. The patient was
asymptomatic and had a history of emergent splenectomy after a high-altitude
falling accident. Abdominal contrast-enhanced computed tomography revealed a 4.5
* 3.3 cm lesion that was located in segment IV of the left liver lobe. The lesion
had an inhomogeneous enhancement during the arterial phase and diminished
enhancement during the portal and equilibrium phases. Similar radiological
features were also observed on a contrast magnetic resonance imaging scan.
Partial hepatectomy was performed with the suspicion of hepatocellular carcinoma.
Pathological examination of the liver specimen revealed intrahepatic splenosis.
CONCLUSION: Splenosis should be considered in differential diagnosis of a liver
mass discovered years after splenic trauma or surgery. A proposed scoring system
may be helpful in evaluating the suspicious degree of intrahepatic mass to be
splenosis. Invasive treatments are not recommended for asymptomatic patients,
since the splenosis can provide beneficial immunologic function.
PMID- 29954391
TI - Obstacles to successful treatment of hepatitis C in uninsured patients from a
minority population.
AB - BACKGROUND: Hepatitis C virus (HCV) treatment regimens (DAAs) are well tolerated,
efficacious but costly. Their high cost and restricted availability, raises
concerns about the outcome of treatment in uninsured patients. This study
investigated sustained virologic response (SVR) outcomes in a predominately
uninsured patient population and completion of four steps along the HCV treatment
cascade. METHODS: A retrospective chart review was conducted to characterize the
patient population and analyze covariates to determine association with insurance
status, attainment of SVR and progression through the HCV treatment cascade.
RESULTS: Out of a total of 216 patients, 154 (71%) were uninsured. Approximately
50% of patients (109 of 216 patients) were male and 57% were Hispanic (123 of 216
patients). Sex, race, ethnicity, treatment compliance, and rates of complications
were not associated with insurance status. Insured patients were older (median 60
years vs 57 years, p-value < 0.001) and had higher rates of cirrhosis: 32 out of
62 patients (52%) vs 48 out of 154 patients (31%) (p-value = 0.005). Insured
patients were tested for SVR at similar rates as uninsured patients: 84% (52 of
62 patients) vs 81% (125 of 154 patients), respectively. Of those tested for SVR,
the cure rate for insured patients was 98% (51 out of 52 patients) compared to
97% (121 out of 125 patients) in the uninsured. Out of those who completed
treatment, 177 of 189 (94%) were tested for attainment of SVR. Compliance rates
were significantly different between tested and untested patients: 88% (156 of
177 patients) vs 0% (0 of 12 patients), respectively (p-value < 0.001). However,
insurance status, race ethnicity, cirrhosis, and complications were not
associated with being tested for SVR. CONCLUSIONS: These results demonstrate that
insured and uninsured patients with chronic HCV infection, with access to patient
assistance programs, can be treated and have comparable clinical outcomes. In
addition, testing for SVR remains an important obstacle in completion of the HCV
treatment cascade. Nevertheless, patient assistance programs remove a significant
barrier for treatment access in real-world HCV infected populations.
PMID- 29954393
TI - CaGdt1 plays a compensatory role for the calcium pump CaPmr1 in the regulation of
calcium signaling and cell wall integrity signaling in Candida albicans.
AB - BACKGROUND: Saccharomyces cerevisiae ScGdt1 and mammalian TMEM165 are two members
of the UPF0016 membrane protein family that is likely to form a new group of
Ca2+/H+ antiporter and/or a Mn2+ transporter in the Golgi apparatus. We have
previously shown that Candida albicans CaGDT1 is a functional ortholog of ScGDT1
in the response of S. cerevisiae to calcium stress. However, how CaGdt1 together
with the Golgi calcium pump CaPmr1 regulate calcium homeostasis and cell wall
integrity in this fungal pathogen remains unknown. METHODS: Chemical sensitivity
was tested by dilution assay. Cell survival was examined by measuring colony
forming units and staining with Annexin V-FITC and propidium iodide. Calcium
signaling was examined by expression of downstream target gene CaUTR2, while cell
wall integrity signaling was revealed by detection of phosphorylated Mkc1 and
Cek1. Subcellular localization of CaGdt1 was examined through direct and indirect
immunofluorescent approaches. Transcriptomic analysis was carried out with RNA
sequencing. RESULTS: This study shows that Candida albicans CaGDT1 is also a
functional ortholog of ScGDT1 in the response of S. cerevisiae to cell wall
stress. CaGdt1 is localized in the Golgi apparatus but at distinct sites from
CaPmr1 in C. albicans. Loss of CaGDT1 increases the sensitivity of cell lacking
CaPMR1 to cell wall and ER stresses. Deletion of CaGDT1 and/or CaPMR1 increases
calcium uptake and activates the calcium/calcineurin signaling. Transcriptomic
profiling reveals that core functions shared by CaGdt1 and CaPmr1 are involved in
the regulation of cellular transport of metal ions and amino acids. However,
CaGdt1 has distinct functions from CaPmr1. Chitin synthase gene CHS2 is up
regulated in all three mutants, while CHS3 is only up regulated in the pmr1/pmr1
and the gdt1/gdt1 pmr1/pmr1 mutants. Five genes (DIE2, STT3, OST3, PMT1 and PMT4)
of glycosylation pathway and one gene (SWI4) of the cell wall integrity (CWI)
pathway are upregulated due to deletion of CaGDT1 and/or CaPMR1. Consistently,
deletion of either CaPMR1 or CaGDT1 activates the CaCek1-mediated CWI signaling
in a cell wall stress-independent fashion. Calcineurin function is required for
the integrity of the cell wall and vacuolar compartments of cells lacking both
GDT1 and CaPMR1. CONCLUSIONS: CaPmr1 is the major player in the regulation of
calcium homeostasis and cell wall stress, while CaGdt1 plays a compensatory role
for CaPmr1 in the Golgi compartment in C. albicans.
PMID- 29954392
TI - Children and young people's participation in developing interventions in health
and well-being: a scoping review.
AB - BACKGROUND: Greater interest is being shown in participatory approaches,
especially in research on interventions that concern children and young people's
health and well-being. Although participatory approaches have user involvement in
common, they differ in terms of the explicit guidance on how to actually involve
and engage children and young people in health research. The aim of this scoping
review was to systematically map recent research involving children and young
people in the development of interventions targeting issues of health and well
being. METHODS: An interpretative scoping literature review based on: a
scientific literature search in (health and social science) databases, reference
lists, a manual search in key journals and contact with existing networks was
conducted. A total of 4458 references were identified through the literature
search, of which 41 studies published between 2000 and 2017 were included in the
review. The target population was children and young people under 25 years old.
Level of participation was categorized according to Shier's Pathways to
Participation Model. RESULTS: The review showed that participatory approaches
were most often used in the development of interventions in school settings and
in community and healthcare settings and on issues concerning support in
lifestyle or in managing illness or disease. The level of participation varied
from children and young people taking part just as active informants, through
stages of greater participation both in quantitative and qualitative terms, to
children and young people becoming an active agent involved as a co-researcher
where the research process was shaped by views of a higher level of mutuality.
Most of the studies were categorised at a medium level and only three studies
were judged to involve the children and young people at the highest level.
CONCLUSIONS: This scoping review showed that work remains in enabling children
and young people to influence the development of interventions targeting health
and well-being. In relation to level of sustainability in the interventions, it
is relevant that goals, strategies and processes are formulated by those who can
gain from the interventions. Participatory approaches aiming for a higher level
of participation where children and young people work together with the
researchers in partnerships are thus warranted.
PMID- 29954394
TI - Facilitation of arthroscopic visualization and treatment of meniscal tears using
a stifle joint distractor in the dog.
AB - BACKGROUND: Stifle arthroscopy has been described to have high sensitivity and
specificity in the evaluation of menisci in dogs, particularly for the medial
meniscus. However, the visualization of menisci can be difficult. The use of
femoral distractors in human medicine has been described to simplify demanding
surgical procedures, such as meniscus transplantation. In veterinary medicine,
stifle distraction has been reported to facilitate access to the joint and
visualization of intra-articular structures, but there are no studies reporting
the use of a stifle distraction technique while performing challenging surgical
procedures, such as meniscal suture, in clinical patients. The objective of this
study was to evaluate the feasibility, effectiveness and safety of stifle
distraction to achieve consistent visualization of menisci and to facilitate
performing arthroscopic procedures in clinical patients with stifle disease.
Initial arthroscopic evaluation of the stifle joint was performed without
distraction in the study population consisting of 13 dogs with naturally
occurring stifle disease. The criteria for inclusion was prospectively set as the
observation of a frank disease or anomaly of the menisci that could not be
further treated or clarified without the risk of damaging the joint cartilage due
to the requested manoeuvres. After the first examination, distraction was applied
in order to complete the assessment of menisci. After achieving an accurate
diagnosis, partial meniscectomy or meniscal repair was performed as needed while
maintaining the distraction. RESULTS: Complete visualization and assessment of
menisci were achieved thanks to the use of distraction. This manoeuvre
facilitated access to the required area of the involved meniscus, and meniscal
treatment could be successfully performed without damaging the articular
cartilage. During the follow-up period, no postoperative complication related to
the distraction or to the arthroscopic procedure was observed. CONCLUSIONS:
Stifle joint distraction during arthroscopy in dogs improves visualization of
both menisci, and particularly the caudal horn of the medial meniscus. Despite
being a subjective assessment, it is the authors' opinion that this procedure
also increases the ease of performing challenging procedures like meniscal
suture, as it enlarges the space available to reach the correct working
angulations.
PMID- 29954395
TI - Evaluation of the predictive value of tonsil examination by bacteriological
culture for detecting positive lung colonization status of nursery pigs exposed
to Actinobacillus pleuropneumoniae by experimental aerosol infection.
AB - BACKGROUND: Actinobacillus (A.) pleuropneumoniae is the causative agent of
porcine pleuropneumonia. For control of the disease the detection of sub
clinically infected pigs is of major importance to avoid transmitting of
subclinical infections. One method recommended is the testing of tonsillar
samples for the presence of A. pleuropneumoniae. This is routinely done by PCR
techniques. However, based upon PCR susceptibility testing and monitoring of
resistance development is impossible. Therefore, in this study the informative
values of bacteriological culture of tonsilar samples for the colonisation status
of pigs were tested. In total, 163 German Landrace nursery pigs were
experimentally exposed to A. pleuropneumoniae serotype 7 by aerosol and the rate
of isolation from lung tissue and tonsils and the corresponding degree of lung
lesions were investigated. RESULTS: Overall a significant correlation (p < 0.001)
between degree of clinical disease, degree of lung alterations and degree of A.
pleuropneumoniae isolation from tonsillar and lung tissue after exposure was
detected. Of these animals tested, 74.8% were tested positive in tonsillar and
lung samples, 7.4% remained completely negative and in 4.3% the tonsils were
tested positive despite negative isolation results from lung tissue. In 13.5% of
the pigs A. pleuropneumoniae could be isolated in lung tissue but not in
tonsillar samples. In 36.4% of these animals a heavy colonization of the lungs
and in 40.9% moderate to severe lung alterations were proven. Hence, the
diagnostic sensitivity for the detection of a positive colonization status of the
pigs by bacterial culture examination of tonsillar samples was 84.7%, the
diagnostic specificity was 66.7% and the predictive values were 94.6% (positive)
and 35.3% (negative). The overall sensitivity for A. pleuropneumoniae exposure
was 78.2% (tonsils) and 88.0% (lung tissue). CONCLUSIONS: In conclusion, tonsil
examination alone for the detection of a positive colonization status of pigs
performed might lead to false negative results as lungs might be heavily
colonized despite negative tonsillar isolation results. Therefore culture of
tonsillar samples should not be the sole test for the confirmation of a pigs'
status but used in combination with methods also evaluating the colonization
status of the lower respiratory tract.
PMID- 29954396
TI - Sheep embryonic stem-like cells engrafted into sheep femoral condyle
osteochondral defects: 4-year follow-up.
AB - BACKGROUND: Articular cartilage lacks a regenerative response. Embryonic stem
cells (ESCs) are a source of pluripotent cells for cartilage regeneration. Their
use, however, is associated with a risk of teratoma development, which depends on
multiple factors including the number of engrafted cells and their degree of
histocompatibility with recipients, the immunosuppression of the host and the
site of transplantation. Colonies of sheep embryonic stem-like (ES-like) cells
from in vitro-produced embryos, positive for stage-specific embryonic antigens
(SSEAs), alkaline phosphatase (ALP), Oct 4, Nanog, Sox 2 and Stat 3 gene
expression, and forming embryoid bodies, were pooled in groups of two-three,
embedded in fibrin glue and engrafted into osteochondral defects in the left
medial femoral condyles of 3 allogeneic ewes (ES). Empty defects (ED) and defects
filled with cell-free glue (G) in the condyles of the controlateral stifle joint
served as controls. After euthanasia at 4 years post-engraftment, the regenerated
tissue was evaluated by macroscopic, histological and immunohistochemical
(collagen type II) examinations and fluorescent in situ hybridization (FISH)
assay to prove the ES-like cells origin of the regenerated tissue. RESULTS: No
teratoma occurred in any of the ES samples. No statistically significant
macroscopic or histological differences were observed among the 3 treatment
groups. FISH was positive in all the 3 ES samples. CONCLUSIONS: This in vivo
preclinical study allowed a long-term evaluation of the occurrence of teratoma in
non-immunosuppressed allogeneic adult sheep engrafted with allogeneic ES-like
cells, supporting the safe and reliable application of ES cells in the clinic.
PMID- 29954397
TI - Assessing adolescents' perceived proficiency in critically evaluating nutrition
information.
AB - BACKGROUND: Over the recent past, there has been an increase in nutrition
information available to adolescents from various sources, which resulted into
confusion and misinterpretation of the dietary advice. Results from international
assessment frameworks such as PISA and TIMMS reflect the need for adolescents to
critically appraise health information. While a number of scales measuring the
critical health literacy of individuals exist; very few of these are devoted to
critical nutrition literacy. More so, these scales target individuals with an
advanced level of nutrition education, often gaging their proficiency in
information appraisal in relation to principles of evidence-based medical
research. The purpose of the present study was to examine the psychometric
properties of a newly developed critical nutrition literacy scale (CNL-E)
measuring adolescents' perceived proficiency in 'critically evaluating nutrition
information from various sources'. METHODS: During spring 2015, more than 1600
tenth graders aged 15-16 years from approximately 60 schools in Norway responded
to the five-item questionnaire using an electronic survey system. Applying Rasch
analysis approach, we examined the psychometric properties of the CNL-E scale
employing the RUMM2030 statistical package. To further investigate the
dimensionality of the scale and test the underlying structure, we applied
multidimensional Rasch modelling using the ConQuest 4 software and confirmatory
factor analysis (CFA) using the Lisrel 9.30 software. RESULTS: In our sample, the
CNL-E stood out as a valid, reliable and well-targeted scale with good overall
fit to the partial credit parameterization of the polytomous unidimensional Rasch
model (PCM). All the items were sufficiently statistically independent, had
ordered response categories and showed acceptable individual fit to the PCM. No
item displayed within-item bias or differential item functioning (DIF).
CONCLUSIONS: From the observed CNL-E sum score, it is possible to draw plausible
conclusions about how individuals critically evaluate nutrition information.
Efforts to improve communication of nutrition information could benefit from
applying validated measures such as the CNL-E scale. The CNL-E scale provides
insight into how individuals without an advanced level of nutrition education,
such as adolescents, determine the validity and reliability of nutrition
information from various sources.
PMID- 29954398
TI - Evaluation of a family-oriented antenatal group educational program in rural
Tanzania: a pre-test/post-test study.
AB - BACKGROUND: To increase births attended by skilled birth attendants in Tanzania,
studies have identified the need for involvement of the whole family in pregnancy
and childbirth education. This study aimed to develop, implement, and evaluate a
family-oriented antenatal group educational program to promote healthy pregnancy
and family involvement in rural Tanzania. METHODS: This was a quasi-experimental
1 group pre-test/post-test study with antenatal education provided to pregnant
women and their families in rural Tanzania. Before and after the educational
program, the pre-test/post-test study was conducted using a 34-item Birth
Preparedness Questionnaire. Acceptability of the educational program was
qualitatively assessed. RESULTS: One-hundred and thirty-eight participants (42
pregnant women, 96 family members) attended the educational program, answered the
questionnaire, and participated in the feasibility inquiry. The mean knowledge
scores significantly increased between the pre-test and the post-test, 7.92 and
8.33, respectively (p = 0.001). For both pregnant women and family members, the
educational program improved Family Support (p = 0.001 and p = 0.000) and
Preparation of Money and Food (p = 0.000 and p = 0.000). For family members, the
scores for Birth Preparedness (p = 0.006) and Avoidance of Medical Intervention
(reversed item) (p = 0.002) significantly increased. Despite the educational
program, the score for Home-based Value (reversed item) (p = 0.022) and
References of SBA (p = 0.049) decreased in pregnant women. Through group
discussions, favorable comments about the program and materials were received.
The comments of the husbands reflected their better understanding and
appreciation of their role in supporting their wives during the antenatal period.
CONCLUSIONS: The family-oriented antenatal group educational program has
potential to increase knowledge, birth preparedness, and awareness of the need
for family support among pregnant women and their families in rural Tanzania. As
the contents of the program can be taught easily by reading the picture drama,
lay personnel, such as community health workers or traditional birth attendants,
can use it in villages. Further development of the Birth Preparedness
Questionnaire is necessary to strengthen the involved factors. A larger scale
study with a more robust Birth Preparedness Questionnaire and documentation of
skilled care use is needed for the next step. TRIAL REGISTRATION: No.2013-273-NA
2013-101 . Registered 12 August 2013.
PMID- 29954399
TI - Tackling injustices of occupational lung disease acquired in South African mines:
recent developments and ongoing challenges.
AB - BACKGROUND: South Africa's mineral resources have produced, and continue to
produce, enormous economic wealth; yet decades of colonialism, apartheid, capital
flight, and challenges in the neoliberal post-apartheid era have resulted in high
rates of occupational lung disease and low rates of compensation for ex-miners
and their families. Given growing advocacy and activism of current and former
mine workers, initiatives were launched by the South African government in 2012
to begin to address the legacy of injustice. This study aimed to assess
developments over the last 5 years in providing compensation, quantify shortfalls
and explore underlying challenges. METHODS: Using the database with compensable
disease claims from over 200,000 miners, the medical assessment database of
400,000 health records and the employment database with 1.6 million miners, we
calculated rates of claims, unpaid claims and shortfall in claim filing for each
of the southern African countries with at least 25,000 miners who worked in South
African mines, by disease type and gender. We also conducted interviews in
Johannesburg, Eastern Cape, Lesotho and a local service unit near a mine site,
supplemented by document review and auto-reflection, adopting the lens of a
critical rights-based approach. RESULTS: By the end of 2017, 111,166 miners had
received compensation (of which 55,864 were for permanent lung impairment, and
another 52,473 for tuberculosis), however 107,714 compensable claims remained
unpaid. Many (28.4%) compensable claims are from Mozambique, Lesotho, Swaziland,
Botswana and elsewhere in southern Africa, a large proportion of which have been
longstanding. A myriad of diverse systemic barriers persist, especially for
workers and their families outside South Africa. Calculating predicted burden of
occupational lung disease compared to compensable claims paid suggests a major
shortfall in filing claims in addition to the large burden of still unpaid
claims. CONCLUSION: Despite progress made, our analysis reveals ongoing complex
barriers and illustrates that the considerable underfunding of the systems
required for sustained prevention and social protection (including compensation)
needs urgent attention. With class action suits in the process of settlement, the
globalized mining sector is now beginning to be held accountable. A critical
rights-based approach underlines the importance of ongoing concerted action by
all.
PMID- 29954400
TI - European Union citizens' views on development assistance for developing
countries, during the recent migrant crisis in Europe.
AB - BACKGROUND: Development assistance from governments of high income countries
represents the vast majority of international funding for global health. Recent
stagnation of this important source of funding may affect attainment of major
global health goals. The financial crisis is widely accredited as denting
governments' outlay for development aid, as well as citizen's support for aid.
Europe has also recently experienced record levels of migration; the so called
'European migration crisis'. This study aims to analyse trends in public
attitudes towards development aid in European Union (EU) countries, in the
context of the European migrant crisis. METHODS: Eurobarometer survey data from
2011 (prior to the migrant crisis) and 2015 (at the peak of the crisis) was
analysed for 27 EU countries. The outcome variables related to people's levels of
support to three statements around the importance of supporting people in
developing countries, increasing countries' commitments to aid and willingness to
pay extra for products from developing countries. EU Member States were
categorised as 'arrival' or 'destination' countries in view of migration routes
and numbers of asylum applications per 100,000 population, respectively. Multiple
linear regression analysis was performed, adjusting for countries' economic
status (gross domestic product per capita). RESULTS: In general, support for
development aid has increased from 2011 to 2015, but was largely unaffected by
migration status when applying the regression model. In 2015, the belief that
development assistance is 'very important' was significantly higher in countries
where migrants first arrived compared to other EU Member States, with a trend
towards this association also apparent in 2011. CONCLUSIONS: The positive trends
in public support for development aid are encouraging in an age where economic
hardships at home, as well as the tone of national political discourses and
rising right wing populism appear to suggest otherwise.
PMID- 29954401
TI - Assisting hand function after spinal cord injury with a fabric-based soft robotic
glove.
AB - BACKGROUND: Spinal cord injury is a devastating condition that can dramatically
impact hand motor function. Passive and active assistive devices are becoming
more commonly used to enhance lost hand strength and dexterity. Soft robotics is
an emerging discipline that combines the classical principles of robotics with
soft materials and could provide a new class of active assistive devices. Soft
robotic assistive devices enable a human-robot interaction facilitated by
compliant and light-weight structures. The scope of this work was to demonstrate
that a fabric-based soft robotic glove can effectively assist participants
affected by spinal cord injury in manipulating objects encountered in daily
living. METHODS: The Toronto Rehabilitation Institute Hand Function Test was
administered to 9 participants with C4-C7 spinal cord injuries to assess the
functionality of the soft robotic glove. The test included object manipulation
tasks commonly encountered during activities of daily living (ADL) and lift force
measurements. The test was administered to each participant twice; once without
the assistive glove to provide baseline data and once while wearing the assistive
glove. The object manipulation subtests were evaluated using a linear mixed
model, including interaction effects of variables such as time since injury. The
lift force measures were separately evaluated using the Wilcoxon signed-rank
test. RESULTS: The soft robotic glove improved object manipulation in ADL tasks.
The difference in mean scores between baseline and assisted conditions was
significant across all participants and for all manipulated objects. An
improvement of 33.42 +/- 15.43% relative to the maximal test score indicates that
the glove sufficiently enhances hand function during ADL tasks. Moreover, lift
force also increased when using the assistive soft robotic glove, further
demonstrating the effectiveness of the device in assisting hand function.
CONCLUSIONS: The results gathered in this study validate our fabric-based soft
robotic glove as an effective device to assist hand function in individuals who
have suffered upper limb paralysis following a spinal cord injury.
PMID- 29954402
TI - Identification of anti-SF3B1 autoantibody as a diagnostic marker in patients with
hepatocellular carcinoma.
AB - BACKGROUND: Tumor-associated (TA) autoantibodies, which are generated by the
immune system upon the recognition of abnormal TA antigens, are promising
biomarkers for the early detection of tumors. In order to detect autoantibody
biomarkers effectively, antibody-specific epitopes in the diagnostic test should
maintain the specific conformations that are as close as possible to those
presenting in the body. However, when using patients' serum as a source of TA
autoantibodies the characterization of the autoantibody-specific epitope is not
easy due to the limited amount of patient-derived serum. METHODS: To overcome
these limits, we constructed a B cell hybridoma pool derived from a
hepatocellular carcinoma (HCC) model HBx-transgenic mouse and characterized
autoantibodies derived from them as tumor biomarkers. Their target antigens were
identified by mass spectrometry and the correlations with HCC were examined. With
the assumption that TA autoantibodies generated in the tumor mouse model are
induced in human cancer patients, the enzyme-linked immunosorbent assays (ELISA)
based on the characteristics of mouse TA autoantibodies were developed for the
detection of autoantibody biomarkers in human serum. To mimic natural antigenic
structures, the specific epitopes against autoantibodies were screened from the
phage display cyclic random heptapeptide library, and the streptavidin antigens
fused with the specific epitopes were used as coating antigens. RESULTS: In this
study, one of HCC-associated autoantibodies derived from HBx-transgenic mouse,
XC24, was characterized. Its target antigen was identified as splicing factor 3b
subunit 1 (SF3B1) and the high expression of SF3B1 was confirmed in HCC tissues.
The specific peptide epitopes against XC24 were selected and, among them, XC24p11
cyclic peptide (-CDATPPRLC-) was used as an epitope of anti-SF3B1 autoantibody
ELISA. With this epitope, we could effectively distinguish between serum samples
from HCC patients (n = 102) and healthy subjects (n = 85) with 73.53% sensitivity
and 91.76% specificity (AUC = 0.8731). Moreover, the simultaneous detection of
anti-XC24p11 epitope autoantibody and AFP enhanced the efficiency of HCC
diagnosis with 87.25% sensitivity and 90.59% specificity (AUC = 0.9081).
CONCLUSIONS: ELISA using XC24p11 peptide epitope that reacts against anti-SF3B1
autoantibody can be used as a novel test to enhance the diagnostic efficiency of
HCC.
PMID- 29954403
TI - The cardiac care bridge program: design of a randomized trial of nurse
coordinated transitional care in older hospitalized cardiac patients at high risk
of readmission and mortality.
AB - BACKGROUND: After hospitalization for cardiac disease, older patients are at high
risk of readmission and death. Although geriatric conditions increase this risk,
treatment of older cardiac patients is limited to the management of cardiac
diseases. The aim of this study is to investigate if unplanned hospital
readmission and mortality can be reduced by the Cardiac Care Bridge transitional
care program (CCB program) that integrates case management, disease management
and home-based cardiac rehabilitation. METHODS: In a randomized trial on patient
level, 500 eligible patients >= 70 years and at high risk of readmission and
mortality will be enrolled in six hospitals in the Netherlands. Included patients
will receive a Comprehensive Geriatric Assessment (CGA) at admission.
Randomization with stratified blocks will be used with pre-stratification by
study site and cognitive status based on the Mini-Mental State Examination (15-23
vs >= 24). Patients enrolled in the intervention group will receive a CGA-based
integrated care plan, a face-to-face handover with the community care registered
nurse (CCRN) before discharge and four home visits post-discharge. The CCRNs
collaborate with physical therapists, who will perform home-based cardiac
rehabilitation and with a pharmacist who advices the CCRNs in medication
management The control group will receive care as usual. The primary outcome is
the incidence of first all-cause unplanned readmission or mortality within 6
months post-randomization. Secondary outcomes at three, six and 12 months after
randomization are physical functioning, functional capacity, depression, anxiety,
medication adherence, health-related quality of life, healthcare utilization and
care giver burden. DISCUSSION: This study will provide new knowledge on the
effectiveness of the integration of geriatric and cardiac care. TRIAL
REGISTRATION: NTR6316 . Date of registration: April 6, 2017.
PMID- 29954404
TI - Laparoscopic right-sided colon resection for colon cancer-has the control group
so far been chosen correctly?
AB - BACKGROUND: The treatment strategies for colorectal cancer located in the right
side of the colon have changed dramatically during the last decade. Due to the
introduction of complete mesocolic excision (CME) with central ligation of the
vessels and systematic lymph node dissection, the long-term survival of affected
patients has increased significantly. It has also been proposed that right-sided
colon resection can be performed laparoscopically with the same extent of
resection and equal long-term results. METHODS: A retrospective evaluation of a
prospectively expanded database on right-sided colorectal cancer or adenoma
treated at the University Hospital of Wuerzburg between 2009 and 2016 was
performed. All patients underwent CME. This data was analyzed alone and in
comparison to the published data describing laparoscopic right-sided colon
resection for colon cancer. RESULTS: The database contains 279 patients, who
underwent right-sided colon resection due to colorectal cancer or colorectal
adenoma (255 open; 24 laparoscopic). Operation data (time, length of stay, time
on ICU) was equal or superior to laparoscopy, which is comparable to the
published results. Surprisingly, the surrogate parameter for correct CME (the
number of removed lymph nodes) was significantly higher in the open group. In a
subgroup analysis only including patients who were feasible for laparoscopic
resection and had been operated with an open procedure by an experienced surgeon,
operation time was significantly shorter and the number of removed lymph nodes is
significantly higher in the open group. CONCLUSION: So far, several studies
demonstrate that laparoscopic right-sided colon resection is comparable to open
resection. Our data suggests that a consequent CME during an open operation leads
to significantly more removed lymph nodes than in laparoscopically resected
patients and in several so far published data of open control groups from Europe.
Further prospective randomized trials comparing the long-term outcome are
urgently needed before laparoscopy for right-sided colon resection can be
recommended ubiquitously.
PMID- 29954405
TI - How can collective action between government sectors to prevent child marriage be
operationalized? Evidence from a post-hoc evaluation of an intervention in Jamui,
Bihar and Sawai Madhopur, Rajasthan in India.
AB - BACKGROUND: Although the need for multi-faceted and multi-sectoral approaches to
address the multidimensional issue of child marriage is well-acknowledged, there
is a dearth of documented experience on the process of implementing and managing
such programmes. METHODS: WHO evaluated a district-level, government-led multi
sectoral intervention to address child marriage in Jamui, Bihar and Sawai
Madhopur, Rajasthan, implemented by MAMTA Health Institute for Mother and Child
(MAMTA). We evaluated the intervention's design, implementation, monitoring, and
outputs and identified key challenges and successes. RESULTS: Through actions at
the state and district levels, the intervention succeeded in creating a cascade
effect to stimulate more concerted action at block and village levels, with
tangible intersectoral convergence occurring at the village level. The success
factors we identified included an experienced partner NGO that was committed to
supporting this effort, context-specific design and implementation, and a
flexible and responsive approach. However, despite contributing to informal
coordination between various stakeholders, the intervention did not succeed in
developing a sustained joint-working mechanism at the district level. Shared
ownership for prioritization of child marriage across national- and state-level
sectors was not established, due in part to lack of directives transcending
ministerial/departmental boundaries. Nevertheless, due to its efforts at the
district-level, the intervention was able to enlist leadership from the District
Magistrates and Child Marriage Prohibition Officers, in line with their duties
outlined in the 2006 Prohibition of Child Marriage Act. The challenges we
identified included lack of clear directives and institutional support for
collaboration, obstacles to monitoring, administrative challenges, differing
perspectives on strategy among district leaders, community resistance, and
intervention over-commitment. CONCLUSIONS: The findings of this evaluation reveal
the potential of multi-sectoral approaches to prevent and respond to child
marriage and provide insight into obstacles that affect multi-sectoral
coordination. We point to actions that MAMTA could take to strengthen
collaboration on this and other initiatives. We also recommend further
documentation and evaluation of projects and programmes in this area.
PMID- 29954406
TI - Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer.
AB - The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) plays essential
roles in embryogenesis and carcinogenesis. IGF2BP1 serves as a post
transcriptional fine-tuner regulating the expression of some essential mRNA
targets required for the control of tumor cell proliferation and growth,
invasion, and chemo-resistance, associating with a poor overall survival and
metastasis in various types of human cancers. Therefore, IGF2BP1 has been
traditionally regarded as an oncogene and potential therapeutic target for
cancers. Nevertheless, a few studies have also demonstrated its tumor-suppressive
role. However, the details about the contradictory functions of IGF2BP1 are
unclear. The growing numbers of microRNAs (miRNAs) and long non-coding RNAs
(lncRNAs) have been identified as its direct regulators, during tumor cell
proliferation, growth, and invasion in multiple cancers. Thus, the mechanisms of
post-transcriptional modulation of gene expression mediated by IGF2BP1, miRNAs,
and lncRNAs in determining the fate of the development of tissues and organs, as
well as tumorigenesis, need to be elucidated. In this review, we summarized the
tissue distribution, expression, and roles of IGF2BP1 in embryogenesis and
tumorigenesis, and focused on modulation of the interconnectivity between IGF2BP1
and its targeted mRNAs or non-coding RNAs (ncRNAs). The potential use of
inhibitors of IGF2BP1 and its related pathways in cancer therapy was also
discussed.
PMID- 29954408
TI - The status of licensed pharmacy workforce in Saudi Arabia: a 2030 economic vision
perspective.
AB - BACKGROUND: The economy of Saudi Arabia is currently undergoing a major
transformation which will have an impact on employment in the pharmacy sector.
However, quantitative data characterizing the pharmacy workforce in the Kingdom
are currently not available. Therefore, the aim of this study was to determine
the current status of the licensed pharmacy workforce in the pharmacy field in
Saudi Arabia. METHODS: Descriptive statistics were performed on data from the
Saudi Commission for Health Specialties (SCFHS) as of March 2017. RESULTS: The
labor market for pharmacists in Saudi Arabia is dominated by expatriates. Saudi
nationals constitute less than 20% of the pharmacists employed in the Kingdom.
The underemployment of Saudis is most evident in the largest sectors of the
pharmacy field, namely, private health care establishments, community pharmacies,
and pharmaceutical companies. CONCLUSION: There is an unmet need to train Saudi
citizens as pharmacists and retain them in the workforce. Addressing this issue
should become an important objective in Saudi Arabia's Vision for 2030.
PMID- 29954407
TI - Health literacy - engaging the community in the co-creation of meaningful health
navigation services: a study protocol.
AB - BACKGROUND: A large proportion of patients encounter barriers to access and
navigation in complex healthcare systems. They are unable to obtain information
and services and to take appropriate action to improve their health. Low health
literacy affects the ability of individuals to benefit from health services. Some
social groups are disproportionately affected by low health literacy, including
those with low educational attainment, Aboriginal people, and those on social
assistance. These individuals face significant barriers in self-management of
chronic diseases and in navigating the healthcare system. For these people,
living in a context of deprivation contributes to maintaining disparities in
access to healthcare and services. The objective of this study is to support
knowledge co-construction and knowledge translation in primary care and services
by involving underserved and Aboriginal people in research. METHODS: This study
will integrate participatory health processes and action research to co-create,
with patients, individuals, and community members impacted by health literacy,
practical recommendations or solutions for facilitating navigation of the
healthcare system by patients, individuals, and community members with less than
optimal health literacy on how to best access health services. With this
approach, academics and those for whom the research is intended will collaborate
closely in all stages of the research to identify findings of immediate benefit
to those impacted by health literacy and work together on knowledge translation.
This study, carried out by researchers, community organizations and groups of
people with low health literacy from three different regions of Quebec and
Saskatchewan who can play an expert role in improving health services, will be
conducted in three phases: 1) data collection; 2) data analysis and
interpretation; and, 3) knowledge translation. DISCUSSION: Persons with low
health literacy experience major obstacles in navigating the health system. This
project will therefore contribute to addressing the gap between healthcare
challenges and the needs of underserved patients with multi-morbidity and/or low
health literacy who have complex health-related needs. It will pave the way for
co-creating successful solutions for and with these communities that will
increase their access to health services.
PMID- 29954409
TI - Development and testing of the Measure of Innovation-Specific Implementation
Intentions (MISII) using Rasch measurement theory.
AB - BACKGROUND: Implementation is proposed to be a multiphase, multilevel process.
After a period of exploration, an adoption decision is made, typically at the
upper management or policy level. Nevertheless, movement through each of the
subsequent phases of the implementation process involves clinicians or providers
at the individual level to adopt the innovation and then change their behavior to
use/deliver the innovation. Multiple behavioral change theories propose that
intentions are a critical determinant of implementation behavior. However, there
is a need for the development and testing of pragmatic measures of providers'
intentions to use a specific innovation or evidence-based practice (EBP).
METHODS: Nine items were developed to assess providers' intentions to use a
specific innovation or EBP. Motivational interviewing was the EBP in the study.
Items were administered, as part of larger survey, to 179 providers across 38
substance use disorder treatment (SUDT) programs within five agencies in
California, USA. Rasch analysis was conducted using RUMM2030 software to assess
the items, their overall fit to the Rasch model, the response scale used,
individual item fit, differential item functioning (DIF), and person separation.
RESULTS: Following a stepwise process, the scale was reduced from nine items to
three items to increase the feasibility and acceptability of the scale while
maintaining suitable psychometric properties. The three-item unidimensional scale
showed good person separation (PSI = .872), no disordering of thresholds, and no
evidence of uniform or non-uniform DIF. Rasch analysis supported the viability of
the scale as a measure of implementation intentions. CONCLUSIONS: The Measure of
Innovation-Specific Implementation Intentions (MISII) is a sound measure of
providers' intentions to use a specific innovation or EBP. Future evaluation of
convergent, divergent, and predictive validity are needed. The study also
demonstrates the value of Rasch analysis for testing the psychometric properties
of pragmatic implementation measures.
PMID- 29954410
TI - Prevalence and diversity of Rickettsia species in ectoparasites collected from
small rodents in Lithuania.
AB - BACKGROUND: Rickettsiae are emerging pathogens causing public health problems in
many countries around the world. Rickettsia spp. are found in association with a
wide range of arthropods which feed on different species of animals. However, the
distribution and natural cycle of Rickettsia species and their association with
different arthropod vectors are not fully established. The aim of this study was
to investigate the presence and prevalence of Rickettsia spp. in ticks, mites and
fleas parasitizing different species of small mammals in Lithuania and to
molecularly characterize the Rickettsia spp. obtained from different
ectoparasites. RESULTS: A total of 1261 ectoparasites (596 Ixodes ricinus ticks,
550 mites of five species and 115 fleas of eight species) collected from 238
rodents in Lithuania during 2013-2014 were investigated for the presence of
Rickettsia pathogens. Infection rates were calculated as the maximum likelihood
estimation (MLE) with 95% confidence intervals (CI). The infection rate varied
among ectoparasites and was found highest in fleas 43.5%, followed by I. ricinus
ticks (MLE = 26.5%; 95% CI: 22.2-31.3%) and then mites (MLE = 9.3%; 95% CI: 7.0
12.2%). Sequence analysis of partial gltA and 17kDa genes revealed the presence
of Rickettsia helvetica, R. felis, R. monacensis, Rickettsia sp. and rickettsial
endosymbionts. Four Rickettsia spp. were identified in fleas, while three
Rickettsia spp. were identified in Laelapidae mites and only one (R. helvetica)
in I. ricinus ticks. CONCLUSIONS: To our knowledge, this is the first report of
the occurrence and molecular characterization of Rickettsia spp. in 11 species of
ectoparasites of small rodents in Lithuania. The present data extend the
knowledge on the distribution of Rickettsia spp. and their association with
different arthropod vectors. Prior to our study, R. felis had never been
identified in Lithuania. To our knowledge, this is also the first report of R.
felis in L. agilis and H. microti mites and in Ct. agyrtes and H. talpae fleas,
as well as the first detection of R. monacensis in Ct. agyrtes fleas.
PMID- 29954411
TI - Immunohistochemical expression of epidermal growth factor receptor (EGFR) in
South Asian head and neck squamous cell carcinoma: association with various risk
factors and clinico-pathologic and prognostic parameters.
AB - BACKGROUND: In this study, we intend to determine the immunohistochemical
expression of EGFR in cases of head and neck squamous cell carcinoma and its
association with prognostic clinico-pathologic features. METHODS: A total of 115
cases of head and neck squamous cell carcinoma treated at Liaquat National
Hospital, Karachi, Pakistan, were included in the study. Clinico-pathologic
features, risk factors, and recurrence status of cases were evaluated, and EGFR
immunohistochemistry was performed. RESULTS: In our study, 52 cases (45.2%) of
head and neck SCC were positive and 10 cases (8.7%) were focal positive for EGFR
expression, while 53 cases (46.1%) were negative for EGFR expression. High EGFR
expression (> 70%) was noted in 6.1% (7 cases), while 12.2% (14 cases) and 26.1%
(30 cases) revealed 51-70% and 11-50% EGFR expression respectively. On the basis
of intensity, strong EGFR expression was noted in 13.9% (16 cases) while 16.5%
(19 cases) and 23.5% (27 cases) revealed intermediate and weak EGFR expression
respectively. Significant association of EGFR expression was noted with tumor
stage and disease-free survival. CONCLUSION: We found a significant association
of EGFR expression with tumor stage and disease-free survivals, which are the
most important prognostic factors in head and neck squamous cell carcinoma;
therefore, EGFR expression can help as a prognostic biomarker in head and neck
squamous cell carcinoma. On the other hand, we suggest that molecular studies
should be performed in squamous cell carcinoma of head and neck in our setup to
identify patients that can avail response from anti-EGFR therapy.
PMID- 29954412
TI - Changing patterns of first e-cigarette flavor used and current flavors used by
20,836 adult frequent e-cigarette users in the USA.
AB - BACKGROUND: Understanding the role that flavors play in the population's use of e
cigarettes and the impact that flavored e-cigarette products have on the
population's use of more harmful tobacco products, like conventional cigarettes,
has been identified by the US Food and Drug Administration (FDA) as a public
health research priority. The purpose of the study was to assess the first e
cigarette flavor and current e-cigarette flavors used by a large non
probabilistic sample of adult frequent users of e-cigarettes in the USA and
assess how flavor preferences vary by cigarette smoking status and time since
first e-cigarette purchase. METHODS: An online survey assessed the first e
cigarette flavor and current e-cigarette flavors used by a non-probabilistic
sample of 20,836 adult frequent e-cigarette users in the USA. Differences in e
cigarette flavor preferences between current smokers, former smokers, and never
smokers and trends in the first flavor used across time of e-cigarette use
initiation were assessed. RESULTS: The majority (n = 15,807; 76.4%) of sampled
frequent e-cigarette users had completely substituted e-cigarettes for
conventional cigarettes-"switchers"-and were currently using rechargeable,
refillable vaping devices. Among them, the proportion of first e-cigarette
purchases that were fruit-flavored increased from 17.8% of first purchases made
before 2011 to 33.5% of first purchases made between June 2015 and June 2016.
Tobacco-flavored first purchases almost halved during this time (46.0% pre-2011
to 24.0% between 2015 and 2016). Fruit/fruit beverage (73.9 to 82.9% of sampled
users), dessert/pastry (63.5 to 68.5% of sampled users), and candy, chocolate, or
sweets (48.7 to 53.4% of sampled users) were the most popular currently used e
cigarette flavors. Tobacco and menthol flavors, the two most popular flavors for
initiating e-cigarette use prior to 2013, now rank as the 5th and 6th most
popular currently used e-cigarette flavors, respectively. CONCLUSIONS: Adult
frequent e-cigarette users in the USA who have completely switched from smoking
cigarettes to using e-cigarettes are increasingly likely to have initiated e
cigarette use with non-tobacco flavors and to have transitioned from tobacco to
non-tobacco flavors over time. Restricting access to non-tobacco e-cigarette
flavors may discourage smokers from attempting to switch to e-cigarettes.
PMID- 29954414
TI - Mortality rate of patients with cystic fibrosis on the waiting list and within
one year after lung transplantation: a survey of Italian CF centers.
AB - BACKGROUND: Cystic Fibrosis (CF) Centers are involved in the decisions regarding
the eligibility of CF patients with end-stage lung disease and timing for
inclusion on waiting lists (WL) for lung transplantation (LT). There are
currently no data on the mortality rates of Italian CF patients on WL and during
the first year after LT and we aimed to assess these outcomes by surveying the CF
Centers. METHODS: A survey was sent to Italian CF Centers which were requested to
report the age at which all CF subjects included on the WL between 2010 and 2014
were included on the list, admitted to either standard or urgent LT, or had died
either while on the WL or within the first 3 and 12 months after LT. All outcomes
were recorded by December 31, 2015. RESULTS: Two hundred fifty-nine CF subjects
were included on the WL during the 5-year study period. The mortality rate during
the WL was 19.3% and was not associated with sex, age at inclusion on the WL or
standard or urgent access to LT. 159 (61.4%) subjects underwent LT, 46 (28.9%)
with urgent procedure. Deaths within the first 3 and 12 months after LT were
significantly more prevalent in individuals who underwent urgent LT compared to
those with standard LT (p < 0.01). CONCLUSIONS: The mortality of Italian CF
patients, included in our survey, was about twice that reported by the National
Transplant Center for all LT indications, including CF, during the same time
period and despite the introduction of urgent LT. The latter was associated with
an unfavorable early outcome compared to standard LT.
PMID- 29954413
TI - Quantitative proteomics of acutely-isolated mouse microglia identifies novel
immune Alzheimer's disease-related proteins.
AB - BACKGROUND: Microglia are innate immune cells of the brain that perform
phagocytic and inflammatory functions in disease conditions. Transcriptomic
studies of acutely-isolated microglia have provided novel insights into their
molecular and functional diversity in homeostatic and neurodegenerative disease
states. State-of-the-art mass spectrometry methods can comprehensively
characterize proteomic alterations in microglia in neurodegenerative disorders,
potentially providing novel functionally relevant molecular insights that are not
provided by transcriptomics. However, comprehensive proteomic profiling of adult
primary microglia in neurodegenerative disease conditions has not been performed.
METHODS: We performed quantitative mass spectrometry based proteomic analyses of
purified CD11b+ acutely-isolated microglia from adult (6 mo) mice in normal,
acute neuroinflammatory (LPS-treatment) and chronic neurodegenerative states
(5xFAD model of Alzheimer's disease [AD]). Differential expression analyses were
performed to characterize specific microglial proteomic changes in 5xFAD mice and
identify overlap with LPS-induced pro-inflammatory changes. Our results were also
contrasted with existing proteomic data from wild-type mouse microglia and from
existing microglial transcriptomic data from wild-type and 5xFAD mice.
Neuropathological validation studies of select proteins were performed in human
AD and 5xFAD brains. RESULTS: Of 4133 proteins identified, 187 microglial
proteins were differentially expressed in the 5xFAD mouse model of AD pathology,
including proteins with previously known (Apoe, Clu and Htra1) as well as
previously unreported relevance to AD biology (Cotl1 and Hexb). Proteins
upregulated in 5xFAD microglia shared significant overlap with pro-inflammatory
changes observed in LPS-treated mice. Several proteins increased in human AD
brain were also upregulated by 5xFAD microglia (Abeta peptide, Apoe, Htra1, Cotl1
and Clu). Cotl1 was identified as a novel microglia-specific marker with
increased expression and strong association with AD neuropathology. Apoe protein
was also detected within plaque-associated microglia in which Apoe and Abeta were
highly co-localized, suggesting a role for Apoe in phagocytic clearance of Abeta.
CONCLUSIONS: We report a comprehensive proteomic study of adult mouse microglia
derived from acute neuroinflammation and AD models, representing a valuable
resource to the neuroscience research community. We highlight shared and unique
microglial proteomic changes in acute neuroinflammation aging and AD mouse models
and identify novel roles for microglial proteins in human neurodegeneration.
PMID- 29954415
TI - Multi-center phase II trial of bortezomib and rituximab maintenance combination
therapy in patients with mantle cell lymphoma after consolidative autologous stem
cell transplantation.
AB - BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive and incurable lymphoma.
Standard of care for younger patients with MCL is induction chemotherapy followed
by autologous stem cell transplantation (auto-HCT). Rituximab maintenance after
auto-HCT has been shown to improve progression-free survival (PFS) and overall
survival (OS) in MCL. Bortezomib maintenance therapy has also been shown to be
tolerable and feasible in this setting. However, the combination of bortezomib
and rituximab as maintenance therapy post-auto-HCT has not been studied. METHODS:
We conducted a multicenter, phase II trial of bortezomib given in combination
with rituximab as maintenance in MCL patients after consolidative auto-HCT.
Enrolled patients (n = 23) received bortezomib 1.3 mg/m2 subcutaneously weekly
for 4 weeks every 3 months (up to 24 months) and rituximab 375 mg/m2
intravenously weekly for 4 weeks every 6 months (up to 24 months) for a total
duration of 2 years. The primary study endpoint was disease-free survival (DFS).
RESULTS: With a median follow-up of 35.9 months, the 2-year DFS probability was
90.2% (95% CI 66-97), and 2-year OS was 94.7% (95% CI 68-99). The most frequent
grade 3/4 toxic events were neutropenia (in 74% of patients) and lymphopenia (in
35%). The incidence of peripheral neuropathy was 48% for grade 1, 9% for grade 2,
and 0% for grade 3/4. We also examined the role of quantitative cyclin D1 (CCND1)
mRNA in monitoring minimal residual disease. CONCLUSION: Combined bortezomib and
rituximab as maintenance therapy in MCL patients following auto-HCT is an active
and well-tolerated regimen. TRIAL REGISTRATION: ClinicalTrials.gov NCT01267812 ,
registered Dec 29, 2010.
PMID- 29954416
TI - Common symptoms for a rare disease in a girl with sarcoidosis: a case report.
AB - BACKGROUND: Sarcoidosis in pediatric age is uncommon and challenging diagnosis,
because manifestations can be significantly variable and non-specific since it is
a multisystem disease, and virtually any organ system may be involved. CASE
PRESENTATION: In this report, we describe the case of a 12-year-old girl
presenting with fatigue and weight loss, with a painless hepato-splenomegaly
without additional clinical signs on physical examination. In our patient, once
we had ruled out infections, malignancies and granulomatous diseases of
childhood, we made diagnosis of sarcoidosis, finding suggestive histological
features in two different tissues (liver and lymph nodes) with lung involvement.
CONCLUSIONS: Our case points out that pediatricians should consider sarcoidosis
in the differential diagnosis in case of systemic symptoms, even in absence of
other specific clinical clues, because they represent the most common clinical
manifestations on presentation in children, in order to refer promptly the young
patient to specialist evaluation.
PMID- 29954417
TI - A study on food-medicine continuum among the non-institutionally trained siddha
practitioners of Tiruvallur district, Tamil Nadu, India.
AB - BACKGROUND: Medicinal properties of the food species are one of the poorly
documented and important areas of ethnopharmacology. The present survey
quantitatively documented the medicinal foods prescribed by the non
institutionally trained siddha practitioners of Tiruvallur district of Tamil
Nadu. METHODS: Field work was carried out between December 2014 and April 2017
using a questionnaire. The illnesses mentioned by the informants were grouped as
illness categories on the basis of emic perceptions. Sufficiency of sampling of
this survey was assessed by plotting the cumulative number of UR and Shannon
Wiener's index. The indices such as informant consensus factor (FIC), Index of
Agreement on Remedies (IAR), and Cultural Food Significance Index (CFSI) were
calculated. RESULTS: This study documented 165 medicinal foods used by 82 non
institutionally trained siddha practitioners of Tiruvallur district, and 73.93%
of these preparations were plant based. Among the animal taxa, 82.05% were
represented by fish taxa. The illness category gastrointestinal ailments is the
majorly cited illness category treated with plant-based formulations. The illness
categories viz., gastrointestinal ailments, hemorrhoids, and neural ailments had
high consensus under the group of plant-based medicinal foods. In animal-based
medicinal foods, kapha ailments had gained 23.07% of UR. The illness categories
such as bone fractures, male reproductive ailments, blood ailments, and anabolic
had high FIC values. CONCLUSIONS: Deeper studies on different dietary cultures of
India may help to derive better interpretations on food-medicine continuum. This
study identified some important claims such as the use of citron, pomegranate and
Solanum americanum (gastrointestinal ailments), Abutilon indicum, onions and
elephant foot yam (hemorrhoids), Boerhavia diffusa (urinary ailments), Moringa
oleifera (anemia), Aloe vera (gynecological ailments), Eclipta prostrata (liver
ailments), ivy gourd (diabetes), citron (hypertension), Centella asiatica
(psychological ailments), spade nose shark (lactogogue), reticulate whipray
(wheezing and bronchitis), Katelysia opima (impotence), Indian squid (anemia),
and Indian oil sardine (anabolic). More studies on these claims will help
identify novel functional foods to add to the field of medical nutrition therapy,
with traditional brand identity. Robust studies on the documentation of the
traditional knowledge on marine resources will yield a good database for various
stakeholders and policy makers.
PMID- 29954418
TI - Long-term Staphylococcus aureus decolonization in patients on home parenteral
nutrition: study protocol for a randomized multicenter trial.
AB - BACKGROUND: Patients with long-term intestinal failure are usually treated by
means of home parenteral nutrition (HPN) where they administer their nutritional
formulation intravenously via a central venous access device (mostly a catheter).
This implies that such patients are exposed to a lifelong risk of developing
Staphylococcus aureus bacteremia (SAB). SAB poses a threat to both catheter and
patient survival and may lead to frequent hospitalization and a permanent loss of
vascular access. In other clinical settings, S. aureus carriage eradication has
been proven effective in the prevention of S. aureus infections. Unfortunately,
there is a complete lack of evidence in HPN support on the most effective and
safe S. aureus decolonization strategy in S. aureus carriers. We hypothesized
that long-term S. aureus decolonization in HPN patients can only be effective if
it is aimed at the whole body (nasal and extra-nasal) and is given chronically or
repeatedly on indication. Besides this, we believe that S. aureus carriage among
caregivers, who are in close contact with the patient, are of great importance in
the S. aureus transmission routes. METHODS/DESIGN: The CARRIER trial is a
randomized, open-label, multicenter clinical trial in Dutch and Danish hospitals
that treat patients on HPN. A total of 138 adult HPN patients carrying S. aureus
will be randomly assigned to a search and destroy (SD) strategy, a quick and
short, systemic antibiotic treatment, or a continuous suppression (CS) strategy,
a repeated chronic topical antibiotic treatment. The primary outcome measure is
the proportion of patients in whom S. aureus is totally eradicated during a 1
year period. Secondary outcomes are time to successful eradication, long-term
antimicrobial resistance, adverse events, patient compliance, incidence of (S.
aureus) infections, catheter removals, mortality rates, S. aureus transmission
routes, quality of life, and health care costs. DISCUSSION: The CARRIER trial is
designed to identify the most safe and effective long-term S. aureus carriage
decolonization strategy in HPN patients. This will eventually lead to a better
understanding of long-term S. aureus decolonization treatments in general. The
results of this study will have a great impact on our daily clinical practice,
which eventually may result in less S. aureus-related infections. TRIAL
REGISTRATION: ClinicalTrials.gov; NCT03173053 . Registered on 1 June 2017.
PMID- 29954419
TI - Multilocus sequence typing of clinical Borreliella afzelii strains: population
structure and differential ability to disseminate in humans.
AB - BACKGROUND: Lyme borreliosis in humans results in a range of clinical
manifestations, thought to be partly due to differences in the pathogenicity of
the infecting strain. This study compared European human clinical strains of
Borreliella afzelii (previously named Borrelia afzelii) using multilocus sequence
typing (MLST) to determine their spatial distribution across Europe and to
establish whether there are associations between B. afzelii genotypes and
specific clinical manifestations of Lyme borreliosis. For this purpose, typing
was performed on 63 strains, and data on a further 245 strains were accessed from
the literature. RESULTS: All 308 strains were categorized into 149 sequence types
(STs), 27 of which are described here for the first time. Phylogenetic and
goeBURST analyses showed short evolutionary distances between strains. Although
the main STs differed among the countries with the largest number of strains of
interest (Germany, the Netherlands, France and Slovenia), the B. afzelii clinical
strains were less genetically structured than those previously observed in the
European tick population. Two STs were found significantly more frequently in
strains associated with clinical manifestations involving erythema migrans,
whereas another ST was found significantly more frequently in strains associated
with disseminated manifestations, especially neuroborreliosis. CONCLUSIONS: The
MLST profiles showed low genetic differentiation between B. afzelii strains
isolated from patients with Lyme borreliosis in Europe. Also, clinical data
analysis suggests the existence of lineages with differential dissemination
properties in humans.
PMID- 29954420
TI - Secondary prevention of early-onset sepsis: a less invasive Italian approach for
managing neonates at risk.
AB - Strategies to prevent early-onset sepsis (EOS) have led to a substantial decline
in many countries. However, one of the most controversial topics in neonatology
is the management of asymptomatic full-term and late preterm neonates at risk for
EOS, and guidelines lack substantial consensus regarding this issue. A strategy
for managing neonates, entirely based on serial physical examinations, has been
developed in two Italian regions. This strategy seems safe, while reducing
laboratory tests and unnecessary antibiotics. In the current commentary we
provide area-based data concerning the prevention of EOS in 2 northern Italian
regions, and we detail the results of their strategy for managing healthy
appearing newborns at risk for EOS.
PMID- 29954421
TI - Cerebrovascular accidents associated with hip fractures: morbidity and mortality
5-year survival.
AB - BACKGROUND: Hip fractures are associated with increased cerebrovascular accidents
(CVAs) in the first postoperative year. Long-term follow-up for CVA and mortality
after hip fracture is lacking. The purpose of this study was to identify risk
factors for CVA and follow mortality in hip fractures in a cohort with greater
than 2 years follow-up. METHODS: We compared past medical history of patients
with hip fractures to long-term survival and the occurrence of CVA. Past medical
history, surgical intervention, CVA occurrence, and death were queried from the
electronic medical recorder system. Level of significance was set at p < 0.05
with 95% confidence interval. RESULTS: Two thousand one hundred ninety-five
patients met inclusion criteria. Mean follow-up was 5 years. One hundred ten
(5.01%) patients were diagnosed with post-fracture CVA. Forty-one patients had
CVA in the first year and 55 patients had CVA between 1 to 5 years after surgery.
Among the potential risk factors, hypertension (HTN), atrial fibrillation (AF),
and diabetes mellitus (DM) had the highest odds ratio for CVA (OR = 1.885, p
value = 0.005; OR = 1.79, p value = 0.012; OR = 1.66, p value = 0.012). The
median survival time in patients with CVA was 51.12 +/- 3.76 months compared to
59.60 +/- 0.93 months in patients without CVA (p = 0.033). CONCLUSIONS: HTN, AF,
and DM are significant risk factors for the occurrence of CVA after hip fracture.
The majority of CVAs occur between the first and fifth year postoperatively, and
CVA is a negative prognostic factor for postoperative survival.
PMID- 29954422
TI - Metabolic reprogramming-based characterization of circulating tumor cells in
prostate cancer.
AB - BACKGROUND: Circulating tumor cells (CTCs), an advantageous target of liquid
biopsy, is an important biomarker for the prognosis and monitoring of cancer.
Currently, detection techniques for CTCs are mainly based on the physical and/or
epithelial characteristics of tumor cells. However, biofunctional activity
markers that can indicate the high metastatic capacity of CTCs are lacking.
METHODS: Functional microarray, quantitative real-time polymerase chain reaction,
and Western blot were used on five prostate cancer cell lines with different
metastatic capacities to identify the metastasis-related metabolic genes. The
identified genes were detected in the CTCs of 64 clinical samples using the RNA
in situ hybridization. A multi-criteria weighted model was used to determine the
optimal metabolic markers for the CTCs test. Based on five fluorescent signals
targeting DAPI, CD45, metabolic, epithelial (EpCAM/CKs), and mesenchymal
(Vimentin/Twist) markers, the filtration-enriched CTCs were classified as
GM+CTCs/GM-CTCs (metabolic types) or E-CTCs/H-CTCs/M-CTCs (EMT types).
Correlation analysis and ROC curve were conducted on 54 prostate cancer samples
to evaluate the clinical significance of CTCs subtypes. RESULTS: Eight metastasis
related metabolic genes were identified, including HK2, PDP2, G6PD, PGK1, PHKA1,
PYGL, PDK1, and PKM2. Among them, PGK1 and G6PD were determined as optimal
glucose metabolic (GM) markers for CTCs. GM+CTCs (marked by PGK1/G6PD) were
detectable in 64.8% (35/54) of prostate cancer patients, accounting for 46.5%
(134/288) of total CTCs. An increased GM+CTCs level was associated with advanced
tumor stage and metastasis (P < 0.05). In the discrimination of cancer
metastasis from non-metastasis, GM+CTCs presented a higher AUC of the ROC curve
(0.780) compared with the EMT CTCs subtypes (E-CTCs 0.729, H-CTCs 0.741, and M
CTCs 0.648). A triple tPSA-Gleason-GM+CTCs marker increased the AUC to 0.904,
which was better than that of the tPSA-Gleason-H-CTCs marker (0.874).
CONCLUSIONS: The metabolic marker (PGK1/G6PD) is determined as the indicator for
the biofunctional activity analysis of CTCs, compared with the existing
morphological (EMT) classification on CTCs. The metabolic characterization of
CTCs demonstrates that hypermetabolic GM+CTCs are promising biomarkers for
prostate cancer metastasis.
PMID- 29954423
TI - Contextualization of psychological treatments for government health systems in
low-resource settings: group interpersonal psychotherapy for caregivers of
children with nodding syndrome in Uganda.
AB - BACKGROUND: Evidence for the effectiveness of psychological treatments in low-
and middle-income countries is increasing. However, there is a lack of systematic
approaches to guide implementation in government health systems. The objective of
this study was to address this gap by employing the Replicating Effective
Programs (REP) framework to guide contextualization of a psychological treatment
in the Uganda public health system for caregivers of children affected by nodding
syndrome, a neuropsychiatric disorder endemic to Sub-Saharan Africa associated
with high morbidity and disability. METHODS: To contextualize a psychological
treatment, we followed the four components of the REP framework: pre-conditions,
pre-implementation, implementation, and maintenance and evolution. A three-step
process involved reviewing health services available for nodding syndrome
affected families and current evidence for psychological treatments, qualitative
formative research, and analysis and documentation of implementation activities.
Stakeholders included members of affected communities, health care workers,
therapists, local government leaders, and Ministry of Health officials. Detailed
written, audio, and video documentation of the implementation activities was used
for content analysis. RESULTS: During the pre-condition component of REP, we
selected group interpersonal therapy (IPT-G) because of its feasibility,
acceptability, effectiveness in the local setting, and availability of locally
developed training materials. During the pre-implementation component, we adapted
the training, logistics, and technical assistance strategies in conjunction with
government and stakeholder working groups. Adaptations included content
modification based on qualitative research with caregivers of children with
nodding syndrome. During the implementation component, training was shortened for
feasibility with government health workers. Peer-to-peer supervision was selected
as a sustainable quality assurance method. IPT-G delivered by community health
workers was evaluated for fidelity, patient outcomes, and other process-level
variables. More than 90% of beneficiaries completed the treatment program, which
was effective in reducing caregiver and child mental health problems. With the
Ministry of Health, we conducted preparatory activities for the maintenance and
evolution component for scale-up throughout the country. CONCLUSIONS: The REP
framework provides a systematic approach to guide contextualization of
psychological treatments for delivery in low-resource public health systems.
Specific recommendations are provided for REP's application in global mental
health. TRIAL REGISTRATION: ISRCTN11382067 ; 08/06/2016; retrospectively
registered.
PMID- 29954424
TI - Detection of Plasmodium berghei infected Anopheles stephensi using near-infrared
spectroscopy.
AB - BACKGROUND: The proportion of mosquitoes infected with malaria is an important
entomological metric used to assess the intensity of transmission and the impact
of vector control interventions. Currently, the prevalence of mosquitoes with
salivary gland sporozoites is estimated by dissecting mosquitoes under a
microscope or using molecular methods. These techniques are laborious,
subjective, and require either expensive equipment or training. This study
evaluates the potential of near-infrared spectroscopy (NIRS) to identify
laboratory reared mosquitoes infected with rodent malaria. METHODS: Anopheles
stephensi mosquitoes were reared in the laboratory and fed on Plasmodium berghei
infected blood. After 12 and 21 days post-feeding mosquitoes were killed, scanned
and analysed using NIRS and immediately dissected by microscopy to determine the
number of oocysts on the midgut wall or sporozoites in the salivary glands. A
predictive classification model was used to determine parasite prevalence and
intensity status from spectra. RESULTS: The predictive model correctly classifies
infectious and uninfectious mosquitoes with an overall accuracy of 72%. The false
negative and false positive rates were 30 and 26%, respectively. While NIRS was
able to differentiate between uninfectious and highly infectious mosquitoes,
differentiating between mid-range infectious groups was less accurate. Multiple
scans of the same specimen, with repositioning the mosquito between scans, is
shown to improve accuracy. On a smaller dataset NIRS was unable to predict
whether mosquitoes harboured oocysts. CONCLUSIONS: To our knowledge, we provide
the first evidence that NIRS can differentiate between infectious and
uninfectious mosquitoes. Currently, distinguishing between different intensities
of infection is challenging. The classification model provides a flexible
framework and allows for different error rates to be optimised, enabling the
sensitivity and specificity of the technique to be varied according to
requirements.
PMID- 29954425
TI - Using a meta-narrative literature review and focus groups with key stakeholders
to identify perceived challenges and solutions for generating robust evidence on
the effectiveness of treatments for rare diseases.
AB - INTRODUCTION: For many rare diseases, strong analytic study designs for
evaluating the efficacy and effectiveness of interventions are challenging to
implement because of small, geographically dispersed patient populations and
underlying clinical heterogeneity. The objective of this study was to integrate
perspectives from published literature and key rare disease stakeholders to
better understand the perceived challenges and proposed methodological approaches
to research on clinical interventions for rare diseases. METHODS: We used a meta
narrative literature review and focus group interviews with key rare disease
stakeholders to better understand the perceived challenges in generating and
synthesizing treatment effectiveness evidence, and to describe various research
methods for mitigating these identified challenges. Data from both components of
this study were synthesized narratively according to research paradigms that
emerged from our data. RESULTS: Results from our meta-narrative literature review
and focus group interviews revealed three fundamental challenges in generating
robust treatment effectiveness evidence for rare diseases: i) limitations in
recruiting a sufficient sample size to achieve planned statistical power; ii)
inability to account for clinical heterogeneity and assess treatment effects
across a clinical spectrum; and iii) reliance on short-term, surrogate outcomes
whose clinical relevance is often unclear. We mapped these challenges and
associated solutions to three interrelated research paradigms: i) explanatory
evidence generation; ii) comparative effectiveness/pragmatic evidence generation;
and iii) patient-oriented evidence generation. Within each research paradigm,
numerous criticisms and potential solutions have been described with respect to
overcoming these challenges from a research study design perspective.
CONCLUSIONS: Over time, discussions about clinical research for interventions for
rare diseases have moved beyond methodological approaches to overcome challenges
related to explanatory evidence generation, with increased recognition of the
importance of pragmatic and patient-oriented evidence. Future directions for our
work include developing a framework to expand current evidence synthesis
practices to take into consideration many of the concepts discussed in this
paper.
PMID- 29954426
TI - The pioneer factor activity of c-Myb involves recruitment of p300 and induction
of histone acetylation followed by acetylation-induced chromatin dissociation.
AB - BACKGROUND: The concept of pioneer transcription factors is emerging as an
essential part of the epigenetic regulation, taking place during cell development
and differentiation. However, the precise molecular mechanism underlying pioneer
factor activity remains poorly understood. We recently reported that the
transcription factor c-Myb acts as a pioneer factor in haematopoiesis, and a
point mutation in its DNA binding domain, D152V, is able to abrogate this
function. RESULTS: Here, we show that specific histone modifications, including
H3K27ac, prevent binding of c-Myb to histone tails, representing a novel effect
of histone modifications, namely restricting binding of a pioneer factor to
chromatin. Furthermore, we have taken advantage of the pioneer-defect D152V
mutant to investigate mechanisms of c-Myb's pioneer factor activity. We show that
c-Myb-dependent transcriptional activation of a gene in inaccessible chromatin
relies on c-Myb binding to histones, as well as on c-Myb interacting with the
histone acetyltransferase p300. ChIP assays show that both wild type and the
D152V mutant of c-Myb bind to a selected target gene at its promoter and
enhancer, but only wild-type c-Myb causes opening and activation of the locus.
Enhancement of histone acetylation restores activation of the same gene in the
absence of c-Myb, suggesting that facilitating histone acetylation is a crucial
part of the pioneer factor function of c-Myb. CONCLUSIONS: We suggest a pioneer
factor model in which c-Myb binds to regions of closed chromatin and then
recruits histone acetyltransferases. By binding to histones, c-Myb facilitates
histone acetylation, acting as a cofactor for p300 at c-Myb bound sites. The
resulting H3K27ac leads to chromatin opening and detachment of c-Myb from the
acetylated chromatin. We propose that the latter phenomenon, acetylation-induced
chromatin dissociation, represents a mechanism for controlling the dynamics of
pioneer factor binding to chromatin.
PMID- 29954427
TI - Aorto-left ventricular tunnel with anomalous origin of right coronary artery and
bicuspid aortic valve: a case report.
AB - BACKGROUND: Aorto-left ventricular tunnel (ALVT) is a rare congenital
extracardiac channel that connects the ascending aorta to the left ventricle. To
our knowledge, no case has been thus far reported as ALVT with both anomalous
origin of right coronary artery (AORCA) and bicuspid aortic valve (BAV). CASE
PRESENTATION: We reported a case of a 5-year-old female diagnosed as ALVT with
accompanying AORCA and BAV which had been previously misdiagnosed as aortic
regurgitation (AR) triggered by BAV. Additionally, a special modality of ALVT was
confirmed in this case during the surgery in which the tunnel was formed by the
separation between the roots of two aortic leaflets during the diastolic period.
CONCLUSIONS: ALVT with both AORCA and BAV is clinically uncommon and the aberrant
tunnel in ALVT can be formed by the gap between the roots of two aortic leaflets.
Besides, ALVT with BAV might easily lead to an inaccurate diagnose as aortic
regurgitation caused by BAV. Cardiac surgeons should be alerted for differential
diagnosis of ALVT with BAV and isolated bicuspid aortic valve (BAV) causing
aortic regurgitation (AR).
PMID- 29954428
TI - Spatial and temporal relationships between human and canine visceral
leishmaniases in Belo Horizonte, Minas Gerais, 2006-2013.
AB - BACKGROUND: Visceral leishmaniasis is a serious public health problem in Brazil,
and control of this disease constitutes a major challenge. The purpose of this
study was to assess the existing spatial and temporal relationships between cases
of canine visceral leishmaniasis (CanL) and human visceral leishmaniasis (HVL)
recorded in Belo Horizonte, State of Minas Gerais, from 2006 to 2013. METHODS:
Data provided by the Belo Horizonte Health Services regarding the disease control
routine were analyzed in order to perform a retrospective observational and
ecological study. Information regarding the incidence rate of HVL and canine
seroprevalence was examined in relation to control actions performed atthe 148
coverage areas of healthcare centers for the period between 2006 and 2013. A time
series analysis was performed using the Gretl 1.9.12 software followed by the
assessment of the existing increasing or declining trend and seasonality in the
occurrence of CanL and HVL. Autoregressive integrated moving average (ARIMA)
models were adjusted, intervention analysis was performed, vector autoregressive
models were developed, and Granger causality was used for testing temporal
relationships between variables. The hot spot analysis tool was used for cluster
identification through Getis-OrdGi statistics. The ArcGis for desktop 10.2.1
software was used for spatial analysis. RESULTS: We identified 866 HVL cases in
Belo Horizonte between 2006 and 2013. The mean proportion of canine
seroprevalence (PCP) was 7.31% and the mean proportion of monitored hosts (PMH)
was 6.73%.HVL and PCP showed a decreasing trend, while PMH increased over time
(P<0.05). Vector Autoregressive (VAR) and Granger analysis showed a temporal
relation between CanL and HVL cases. Maps illustrating the spatial distribution
of cases and obituaries of HVL and CanL cases also showed an apparent association
between the occurrence of leishmaniasis in humans, and data about canine cases
recorded in the previous years. CONCLUSIONS: Cases of HVL were preceded by PMH
and PCP cases. Similar results were observed for intraspecific cases (i.e.
between PCP and other canine cases and between HVL and other HVL cases), which
indicated the existence of favorable environmental conditions for the
transmission and spread of L. infantum in Belo Horizonte.
PMID- 29954429
TI - Successful emergent repair of a subacute left ventricular free wall rupture after
acute inferoposterolateral myocardial infarction.
AB - BACKGROUND: Myocardial rupture is an important and catastrophic complication of
acute myocardial infarction. A dramatic form of this complication is a left
ventricular free wall rupture (LVFWR). CASE PRESENTATION: A 70-year-old man with
acute inferoposterolateral myocardial infarction and single-vessel coronary
artery disease underwent emergency percutaneous coronary intervention (PCI). The
circumflex coronary artery was successfully stented with a drug-eluting stent.
Fifty days after PCI the patient experienced progressive fatigue and chest pain
with haemodynamic instability. Transthoracic echocardiography showed a covered
LVFWR of the lateral wall. The patient underwent successful emergent surgical
repair of the LVFWR. CONCLUSIONS: In the current era of swift PCI, mechanical
complications of acute myocardial infarction, such as LVFWR, are rare. The
consequences, however, are haemodynamic deterioration and imminent death. This
rare diagnosis should always be considered when new cardiovascular symptoms or
haemodynamic instability develop after myocardial infarction, even beyond one
month after the initial event. Timely diagnosis and emergency surgery are
required for successful treatment of this devastating complication.
PMID- 29954430
TI - Sustainability issues of commercial non-timber forest product extraction in West
Suriname.
AB - BACKGROUND: Non-timber forest products (NTFPs) have been traded for millennia by
indigenous communities. Current increased demands driven by globalisation,
however, put more pressure on local harvesters and their surrounding ecosystems.
The safeguarding of indigenous access rights to harvesting grounds is needed,
either through communal land titles or collaborative management agreements, both
to secure prior indigenous rights and to minimise further negative ecological
impacts. METHODS: This study was carried out in two indigenous communities in
West Suriname located along the Corentyne River. We assessed the three
economically most important NTFPs for each community. We determined the land
tenure status of harvesting grounds and negative impacts on target species and/or
ecosystem. Ethnobotanical data were collected (n = 53), and semi-structured
interviews were held with hunters and gatherers (n = 13). Local and national maps
were acquired, and their data merged. RESULTS: Results showed that the
communities have no tenure security over their most important harvesting sites.
These collection sites are State owned and some under (active) logging
concession. All of the traded wild animal populations had decreased because of
increased local and non-local commercial interest, especially the stingray
Potamotrygon boesemani (first described in 2008), which was traded for US$250 per
live specimen. The stingray population had become imperilled within months as
local and (inter-) national regulations for this species are non-existent.
CONCLUSIONS: We stress the urgent need for collaborative management agreements
over the harvesting sites between the government of Suriname and the indigenous
communities to prevent further non-local developments and harvesting to disturb
the local economy. An immediate moratorium on the export of P. boesemani is
necessary to prevent the extinction of this endemic stingray.
PMID- 29954431
TI - Reprogramming the murine colon cancer microenvironment using lentivectors
encoding shRNA against IL-10 as a component of a potent DC-based
chemoimmunotherapy.
AB - BACKGROUND: The excessive amounts of immunosuppressive factors present in a tumor
microenvironment (TME) reduce the effectiveness of cancer vaccines. The main
objective of our research was to improve the effectiveness of dendritic cell (DC)
based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and
DCs by application of lentivectors encoding shRNA specific to IL-10 (shIL10 LVs)
in murine colon carcinoma MC38 model. METHODS: The efficacy of shIL10 LVs in
silencing of IL-10 expression was measured both in vitro and in vivo using Real
Time PCR and ELISA assays. In addition, the influence of intratumorally
inoculated lentivectors on MC38 tumor microenvironment was examined using flow
cytometry method. The effect of applied therapeutic schemes was determined by
measurement of tumor growth inhibition and activation state of local and systemic
immune response. RESULTS: We observed that intratumorally inoculated shIL10 LVs
transduced tumor and TME-infiltrating cells and reduced the secretion of IL-10.
Application of shIL10 LVs for three consecutive weeks initiated tumor growth
inhibition, whereas treatment with shIL10 LVs and BMDC/TAg did not enhance the
antitumor effect. However, when pretreatment with CY was introduced to the
proposed scheme, we noticed high MC38 tumor growth inhibition accompanied by
reduction of MDSCs and Tregs in TME, as well as activation of potent local and
systemic Th1-type antitumor response. CONCLUSIONS: The obtained data shows that
remodeling of TME by shIL10 LVs and CY enhances DC activity and supports them
during regeneration and actuation of a potent antitumor response. Therefore,
therapeutic strategies aimed at local IL-10 elimination using lentiviral vectors
should be further investigated in context of combined chemoimmunotherapies.
PMID- 29954432
TI - Signatures of ecological processes in microbial community time series.
AB - BACKGROUND: Growth rates, interactions between community members, stochasticity,
and immigration are important drivers of microbial community dynamics. In
sequencing data analysis, such as network construction and community model
parameterization, we make implicit assumptions about the nature of these drivers
and thereby restrict model outcome. Despite apparent risk of methodological bias,
the validity of the assumptions is rarely tested, as comprehensive procedures are
lacking. Here, we propose a classification scheme to determine the processes that
gave rise to the observed time series and to enable better model selection.
RESULTS: We implemented a three-step classification scheme in R that first
determines whether dependence between successive time steps (temporal structure)
is present in the time series and then assesses with a recently developed
neutrality test whether interactions between species are required for the
dynamics. If the first and second tests confirm the presence of temporal
structure and interactions, then parameters for interaction models are estimated.
To quantify the importance of temporal structure, we compute the noise-type
profile of the community, which ranges from black in case of strong dependency to
white in the absence of any dependency. We applied this scheme to simulated time
series generated with the Dirichlet-multinomial (DM) distribution, Hubbell's
neutral model, the generalized Lotka-Volterra model and its discrete variant (the
Ricker model), and a self-organized instability model, as well as to human stool
microbiota time series. The noise-type profiles for all but DM data clearly
indicated distinctive structures. The neutrality test correctly classified all
but DM and neutral time series as non-neutral. The procedure reliably identified
time series for which interaction inference was suitable. Both tests were
required, as we demonstrated that all structured time series, including those
generated with the neutral model, achieved a moderate to high goodness of fit to
the Ricker model. CONCLUSIONS: We present a fast and robust scheme to classify
community structure and to assess the prevalence of interactions directly from
microbial time series data. The procedure not only serves to determine ecological
drivers of microbial dynamics, but also to guide selection of appropriate
community models for prediction and follow-up analysis.
PMID- 29954433
TI - Multiplexed-tandem PCR (MT-PCR) assay to detect and differentiate
gastrointestinal nematodes of alpacas.
AB - BACKGROUND: Gastrointestinal nematodes (GINs) frequently infect South American
camelids (alpacas and llamas) and cause economic losses due to reduced production
of fiber, meat and/or leather. Our knowledge about the epidemiology and diagnosis
of GINs in llamas and alpacas is limited, and reliable keys for the
identification of the third-stage larvae (L3s) of some common nematodes (such as
Camelostrogylus mentulatus) that infect alpacas and llamas remain undescribed. In
this study, we modified two existing semi-quantitative multiplexed-tandem (MT)
PCR assays, originally developed for the GINs of sheep and cattle, to reliably
detect and differentiate the common genera/species of GINs in the faeces of
alpacas. RESULTS: Following the establishment of the MT-PCR assay using positive
and negative control samples, alpaca faecal samples were tested to validate the
assay to detect and differentiate nematode genera/species, including C.
mentulatus, Cooperia spp., Haemonchus spp., Oesophagostomum spp., Ostertagia
ostertagi, Teladorsagia circumcincta and Trichostrongylus spp. Sequencing of the
MT-PCR products demonstrated specific (100%) amplification of the target nematode
genera/species. Additionally, a comparison of results of the MT-PCR assay and the
morphological identification of adult worms collected from the same 35 alpacas
revealed that there was a good agreement (37-94%) between the two methods.
However, some discrepancies were observed between the results of the MT-PCR assay
and the morphological identification of adult worms. CONCLUSIONS: The MT-PCR
platform is an accurate, sensitive and rapid method for the diagnosis of GINs in
alpacas, and it can be used as a substitute to larval culture to identify common
nematodes in the faeces of alpacas and llamas.
PMID- 29954434
TI - Early versus late intramedullary nailing for traumatic femur fracture management:
meta-analysis.
AB - INTRODUCTION: There is no consensus yet on the impact of timing of femur fracture
(FF) internal fixation on the patient outcomes. This meta-analysis was conducted
to evaluate the contemporary data in patients with traumatic FF undergoing
intramedullary nail fixation (IMN). METHODS: English language literature was
searched with publication limits set from 1994 to 2016 using PubMed, Scopus,
MEDLINE (OVID), EMBASE (OVID), Web of Science, and Cochrane Central Register of
Controlled Trials (CENTRAL). Studies included randomized controlled trials
(RCTs), prospective observational or retrospective cohort studies, and case
control studies comparing early versus late femoral shaft fractures IMN fixation.
Variable times were used across studies to distinguish between early and late
IMN, but 24 h was the most frequently used cutoff. The quality assessment of the
reviewed studies was performed with two instruments. Observational studies were
assessed with the Newcastle-Ottawa Quality Assessment Scale. RCTs were assessed
with the Cochrane Risk of Bias Tool. RESULTS: We have searched 1151 references.
Screening of titles and abstracts eliminated 1098 references. We retrieved 53
articles for full-text screening, 15 of which met study eligibility criteria.
CONCLUSIONS: This meta-analysis addresses the utility of IMN in patients with FF
based on the current evidence; however, the modality and timing to intervene
remain controversial. While we find large pooled effects in favor of early IMN,
for reasons discussed, we have little confidence in the effect estimate.
Moreover, the available data do not fill all the gaps in this regard; therefore,
a tailored algorithm for management of FF would be of value especially in
polytrauma patients.
PMID- 29954435
TI - Host specificity and species diversity of the Ostertagiinae Lopez-Neyra, 1947 in
ruminants: a European perspective.
AB - BACKGROUND: Nematodes of the subfamily Ostertagiinae appear to be rather specific
to a species or family of hosts, but some are observed in a wide variety of
hosts. The nematode Ostertagia leptospicularis draws special attention due to its
presence or absence among the same host species in different European countries.
Therefore, this paper focuses mainly on the host specificity among nematodes of
the subfamily Ostertagiinae. The second aim of this study is to assess the
possibility of treating O. leptospicularis as an Ostertagia species complex.
METHODS: Data were gathered from post-mortem examinations of domestic and wild
ruminants (n = 157), as well as bibliographical references (n = 96), which were
pooled and discussed. The research area was limited to European countries, hence
the studied ostertagiine species are limited to native ones; likewise, the host
species. Special emphasis was placed on the mean abundance values that allowed a
typical host or hosts for each nematode species to be specified. Correspondence
analysis was performed to confirm the stated host specificity. RESULTS: The
analysis revealed that nematodes of this subfamily tend to use ruminants from a
particular subfamily as their principal host. The results indicate that
Ostertagia leptospicularis, similar to Teladorsagia circumcincta, may represent a
potential species complex. This nematode, as the sole member of the subfamily
Ostertagiinae, occurs in almost all representatives of the Bovidae subfamily, as
well as in the Cervidae. CONCLUSIONS: Despite the stated narrow host specificity,
the results obtained may suggest that O. leptospicularis is not strongly
connected to any host or is comparably associated with a very wide and diverse
group of hosts (Cervidae, Bovidae). The Ostertagia complex may have particular
cryptic species or strains typical for any individual host or group of hosts.
Such a conclusion requires further investigations on a wider scale.
PMID- 29954436
TI - Second month sputum smear as a predictor of tuberculosis treatment outcomes in
Brazil.
AB - OBJECTIVE: The value of sputum smear microscopy (SSM) after 2 months of treatment
in the management of pulmonary tuberculosis is controversial. We analysed second
month-SSM conversion as a predictor of treatment success in Brazil. RESULTS:
Overall successful outcome rate was 89.4%. The predictive value of second month
SSM conversion for successful outcomes was 85.2% 72,479/85,118), while the
predictive value of non-conversion for unfavourable outcomes was 26.9%
(2712/10,071). Unfavourable treatment outcomes were twice more likely among
patients who did not convert (adjusted OR = 2.06; 1.97-2.16).
PMID- 29954437
TI - Augmented antitumor activity by olaparib plus AZD1775 in gastric cancer through
disrupting DNA damage repair pathways and DNA damage checkpoint.
AB - BACKGROUND: Targeting poly ADP-ribose polymerase (PARP) has been recently
identified as a promising option against gastric cancer (GC). However, PARP
inhibitors alone achieve limited efficacy. Combination strategies, especially
with homologous recombination (HR) impairment, are of great hope to optimize PARP
inhibitor's efficacy and expand target populations but remains largely unknown.
Herein, we investigated whether a WEE1/ Polo-like kinase 1 (PLK1) dual inhibitor
AZD1775 reported to impair HR augmented anticancer activity of a PARP inhibitor
olaparib and its underlying mechanisms. METHODS: GC cell lines and in vivo
xenografts were employed to determine antitumor activity of PARP inhibitor
combined with WEE1/PLK1 dual inhibitor AZD1775. Western blot, genetic knockdown
by siRNA, flow cytometry, Immunohistochemistry were performed to explore the
underlying mechanisms. RESULTS: AZD1775 dually targeting WEE1/PLK1 enhanced
effects of olaparib on growth inhibition and apoptotic induction in GC cells.
Mechanistic investigations elucidate that WEE1/PLK1 blockade downregulated
several HR-related proteins and caused an accumulation in gammaH2AX. As confirmed
in both GC cell lines and mice bearing GC xenografts, these effects were enhanced
by AZD1775-olaparib combination compared to olaparib alone, suggesting that
disrupting HR-mediated DNA damage repairs (DDR) by WEE1/PLK1 blockade might be
responsible for improved GC cells' response to PARP inhibitors. Given the DNA
damage checkpoint as a primary target of WEE1 inhibition, our data also
demonstrate that AZD1775 abrogated olaparib-activated DNA damage checkpoint
through CDC2 de-phosphorylation, followed by mitotic progression with unrepaired
DNA damage (marked by increased pHH3-stained and gammaH2AX-stained cells,
respectively). CONCLUSIONS: PARP inhibitor olaparib combined with WEE1/PLK1 dual
inhibitor AZD1775 elicited potentiated anticancer activity through disrupting DDR
signaling and the DNA damage checkpoint. It sheds light on the combination
strategy of WEE1/PLK1 dual inhibitors with PARP inhibitors in the treatment of
GC, even in HR-proficient patients.
PMID- 29954438
TI - Epidemiology and economic impact of bovine cysticercosis and taeniosis caused by
Taenia saginata in northeastern Spain (Catalonia).
AB - BACKGROUND: In Catalonia (north-eastern Spain), Taenia saginata has been
described in cattle but its occurrence in humans is unclear. Moreover, whether
cattle acquired the infection in Catalonia or outside Catalonia and its economic
impact have not been investigated. This study aimed to estimate the prevalence
and spatial distribution of bovine cysticercosis in Catalonia (2008-2015), and
the burden from T. saginata upon the animal and human sectors in Catalonia (2013
2015). METHODS: Data on cattle diagnosed with cysticercosis at meat inspection
were collected and analysed. Cattle movement history was used to identify the
most likely place of bovine cysticercosis infection and to investigate its
spatial distribution. Data on taeniosis treatment (niclosamide and praziquantel)
costs and their supply in Catalonia as well as data on patients attending primary
care with diagnosis of taeniosis were collected. The financial impact associated
with T. saginata due to carcasses condemned and frozen, meat inspection and human
taeniosis was estimated. RESULTS: During 2008-2015, between 18 and 107 cattle
were found positive for cysticercosis each year (prevalence at slaughter of
0.010%). Movement history was available for 44% of the infected cattle and in 53%
of them Catalonia was identified as the place where the infection was acquired
with highest probability. Two significant bovine cysticercosis clusters were
detected. The number of patients diagnosed with taeniosis in primary care during
the period 2013-2016 was 41-63/year. The overall economic impact of T. saginata
(2013-2015) amounted to 154,903 ?/year (95% CI: 113,075-196,762). Meat inspection
accounted for 81.9% (95% CI: 75.8-86.2%) of the costs, followed by costs due to
carcass condemnation and freezing (9.4%; 95% CI: 6.9-12.8%), and taeniosis
associated costs (8.7%; 95% CI: 6.7-11.6%). Costs due to freezing and
condemnation of carcasses reached 19,442 ?/year (95% CI: 17,528-21,391) (509
?/lightly infected carcass and 1,140 ?/heavily infected carcass). Taeniosis
associated costs were estimated at 12,848.5 ?/year (237 ?/patient). CONCLUSIONS:
The public health risk of T. saginata in the area seems to be low. The economic
impact due to T. saginata was mainly attributed to meat inspection. The cost due
to carcass condemnation and freezing was limited compared to the revenue of the
beef sector. Developing and implementing risk-based surveillance is needed to
lower the costs of meat inspection. Considering cattle movements might be useful
in the development of such a strategy.
PMID- 29954439
TI - Abundance of clinical variants in exons included in multiple transcripts.
AB - Previous studies showed that the magnitude of selection pressure in constitutive
exons is higher than that in alternatively spliced exons. The intensity of
selection was also shown to be depended on the inclusion level of exons: the
number of transcripts that include an exon. Here, we examined how the difference
in selection pressure influences the patterns of clinical variants in human
exons. Our analysis revealed a positive relationship between exon inclusion level
and the abundance of pathogenic variants. The proportion of pathogenic variants
in the exons that are included in > 10 transcripts was 6.8 times higher than
those in the exons included in only one transcript. This suggests that the
mutations occurring in the exons included in multiple transcripts are more
deleterious than those present in the exons included in one transcript. The
findings of this study highlight that the exon inclusion level could be used to
predict the mutations associated with diseases.
PMID- 29954440
TI - NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through
ERK phosphorylation.
AB - Pruritus is the most common complication of intrathecal morphine; however, its
exact molecular mechanism is unclear, and treatment is challenging. The analgesic
effect of N-methyl-D-aspartate (NMDA) receptor antagonists and the morphine
associated increase in NMDA receptor activation suggest potential role of NMDA
receptor in the spinal itch sensation. Male C57BL/6 mice were given intrathecal
morphine to induce scratching behavior. The effects of NMDA, ketamine, ifenprodil
and U0126 on morphine-induced pruritus and analgesia were evaluated also. The
number of scratching responses was counted for 30 min post-injection to evaluate
pruritus. A warm-water tail immersion assay was conducted before and until 120
min post-injection at 30-min intervals. Percent of maximal possible effect (%MPE)
and area under curve (AUC) were calculated based on tail-flick latency to
evaluate analgesic efficacy. Compared with control treatment, intrathecal
morphine elicited an obvious scratching response and analgesic effect in a dose
dependent manner. Ketamine (1 MUg), ifenprodil (0.1 MUg) and U0126 (0.1 MUg and
1.0 MUg) all significantly attenuated morphine induced scratches. Ifenprodil (0.1
MUg) injection significantly prolonged the analgesic effect of intrathecal
morphine. The ERK1/2 phosphorylation induced by intrathecal morphine was
inhibited by ketamine, ifenprodil and U0126 as well. U0126 inhibited morphine
induced pruritus with no effect on its analgesia. Therefore, intrathecal
coadministration of morphine with NMDA receptor antagonists ketamine and
ifenprodil alleviated morphine-induced scratching. Intrathecal morphine increased
ERK phosphorylation in the lumbar spinal dorsal horn, which may be related with
morphine-induced pruritus, and was counteracted by NMDA receptor antagonists.
PMID- 29954441
TI - INSaFLU: an automated open web-based bioinformatics suite "from-reads" for
influenza whole-genome-sequencing-based surveillance.
AB - BACKGROUND: A new era of flu surveillance has already started based on the
genetic characterization and exploration of influenza virus evolution at whole
genome scale. Although this has been prioritized by national and international
health authorities, the demanded technological transition to whole-genome
sequencing (WGS)-based flu surveillance has been particularly delayed by the lack
of bioinformatics infrastructures and/or expertise to deal with primary next
generation sequencing (NGS) data. RESULTS: We developed and implemented INSaFLU
("INSide the FLU"), which is the first influenza-oriented bioinformatics free web
based suite that deals with primary NGS data (reads) towards the automatic
generation of the output data that are actually the core first-line "genetic
requests" for effective and timely influenza laboratory surveillance (e.g., type
and sub-type, gene and whole-genome consensus sequences, variants' annotation,
alignments and phylogenetic trees). By handling NGS data collected from any
amplicon-based schema, the implemented pipeline enables any laboratory to perform
multi-step software intensive analyses in a user-friendly manner without previous
advanced training in bioinformatics. INSaFLU gives access to user-restricted
sample databases and projects management, being a transparent and flexible tool
specifically designed to automatically update project outputs as more samples are
uploaded. Data integration is thus cumulative and scalable, fitting the need for
a continuous epidemiological surveillance during the flu epidemics. Multiple
outputs are provided in nomenclature-stable and standardized formats that can be
explored in situ or through multiple compatible downstream applications for fine
tuned data analysis. This platform additionally flags samples as "putative mixed
infections" if the population admixture enrolls influenza viruses with clearly
distinct genetic backgrounds, and enriches the traditional "consensus-based"
influenza genetic characterization with relevant data on influenza sub-population
diversification through a depth analysis of intra-patient minor variants. This
dual approach is expected to strengthen our ability not only to detect the
emergence of antigenic and drug resistance variants but also to decode
alternative pathways of influenza evolution and to unveil intricate routes of
transmission. CONCLUSIONS: In summary, INSaFLU supplies public health
laboratories and influenza researchers with an open "one size fits all"
framework, potentiating the operationalization of a harmonized multi-country WGS
based surveillance for influenza virus. INSaFLU can be accessed through
https://insaflu.insa.pt .
PMID- 29954442
TI - Supervillin promotes epithelial-mesenchymal transition and metastasis of
hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38
pathway.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant
tumors in the world and metastasis is the leading cause of death associated with
HCC. Hypoxia triggers the epithelial-mesenchymal transition (EMT) of cancer
cells, which enhances their malignant character and elevates metastatic risk.
Supervillin associates tightly with the membrane and cytoskeleton, promoting cell
motility, invasiveness, and cell survival. However, the roles of supervillin in
HCC metastasis remain unclear. METHODS: Tissue microarray technology was used to
immunohistochemically stain for supervillin antibody in 173 HCC tissue specimens
and expression levels correlated with the clinicopathological variables. Tumor
cell motility and invasiveness, as well as changes in the mRNA expression levels
of genes associated with cancer cell EMT, were investigated. The relationship
between supervillin and Rho GTPases was examined using Co-IP and GST pull-down.
RESULTS: Hypoxia-induced upregulation of supervillin promoted cancer cell
migration and invasion via the activation of the ERK/p38 pathway downstream of
RhoA/ROCK signaling. Furthermore, supervillin regulated the expression of EMT
genes during hypoxia and accelerated the metastasis of HCC in vivo. CONCLUSIONS:
Hypoxia-induced increase in supervillin expression is a significant and
independent predictor of cancer metastasis, which leads to poor survival in HCC
patients. Our results suggest that supervillin may be a candidate prognostic
factor for HCC and a valuable target for therapy.
PMID- 29954443
TI - Empirical optimization of risk thresholds for dengue: an approach towards
entomological management of Aedes mosquitoes based on larval indices in the Kandy
District of Sri Lanka.
AB - BACKGROUND: Larval indices such as Premise Index (PI), Breteau Index (BI) and
Container Index (CI) are widely used to interpret the density of dengue vectors
in surveillance programmes. These indices may be useful for forecasting disease
outbreaks in an area. However, use of the values of these indices as alarm
signals is rarely considered in control programmes. Therefore, the current study
aims to propose threshold values for vector indices based on an empirical
modeling approach for the Kandy District of Sri Lanka. METHODS: Monthly vector
indices, viz PI, BI and CI, for Aedes aegypti and Aedes albopictus, of four
selected dengue high risk Medical Officer of Health (MOH) areas in the Kandy
District from January 2010 to August 2017, were used in the study. Gumbel
frequency analysis was used to calculate the exceedance probability of
quantitative values for each individual larval index within the relevant MOH
area, individually and to set up the threshold values for the entomological
management of dengue vectors. RESULTS: Among the study MOH areas, Akurana
indicated a relatively high density of both Ae. aegypti and Ae. albopictus, while
Gangawata Korale MOH area had the lowest. Based on Ae. aegypti, threshold values
were defined for Kandy as low risk (BIagp > 1.77), risk (BIagp > 3.23), moderate
risk (BIagp > 4.47) and high risk (BIagp > 6.23). In addition, PI > 6.75 was
defined as low risk, while PI > 9.43 and PI>12.82 were defined as moderate and
high risk, respectively as an average. CONCLUSIONS: Threshold values recommended
for Ae. aegypti (primary vector for dengue) along with cut-off values for PI (for
Ae. aegypti and Ae. albopictus), could be suggested as indicators for decision
making in vector control efforts. This may also facilitate the rational use of
financial allocations, technical and human resources for vector control
approaches in Sri Lanka in a fruitful manner.
PMID- 29954444
TI - Differential incidence trends of colon and rectal cancers in Hong Kong: an age
period-cohort analysis.
AB - BACKGROUND: Colorectal cancer has been the second most common cancer among men
and women in Hong Kong since 2012, but the underlying reasons for this increase
remain unclear. We describe the incidence trend for colorectal cancer in Hong
Kong to explore its etiology within this population. METHODS: The temporal trends
in colorectal cancer incidence between 1983 and 2012 were analyzed with joinpoint
regressions by sex, age groups, and anatomic sites among adults using data from
the Hong Kong Cancer Registry. An age-period-cohort analysis was used to evaluate
the effects of age, calendar periods, and birth cohorts on the observed temporal
trends. RESULTS: The incidence of colon cancer among those aged 50 years and
older in both sexes increased steadily from 1983 until the mid-1990s and was
followed by a slight decrease thereafter, whereas the incidence among those aged
20-49 years decreased steadily from 1983 to 2012. In contrast, the incidence of
rectal cancer steadily increased in men and remained stable in women throughout
the study period. Significant period and birth cohort effects were observed for
colon cancer, whereas period effects on the temporal trends were observed for
male rectal cancer. CONCLUSIONS: The incidences of colon and rectal cancers have
exhibited divergent patterns between 1983 and 2012 in Hong Kong, indicating
heterogeneous etiologies between these two types of cancers. Surveillance of the
risk factors related to colon and rectal cancers in the Hong Kong population
should be performed, and the increased rectal cancer incidence in males is worthy
of extra attention.
PMID- 29954445
TI - Non-inflammatory tumor microenvironment of diffuse intrinsic pontine glioma.
AB - Diffuse intrinsic pontine glioma (DIPG) is a universally fatal malignancy of the
childhood central nervous system, with a median overall survival of 9-11 months.
We have previously shown that primary DIPG tissue contains numerous tumor
associated macrophages, and substantial work has demonstrated a significant
pathological role for adult glioma-associated macrophages. However, work over the
past decade has highlighted many molecular and genomic differences between
pediatric and adult high-grade gliomas. Thus, we directly compared inflammatory
characteristics of DIPG and adult glioblastoma (GBM). We found that the leukocyte
(CD45+) compartment in primary DIPG tissue samples is predominantly composed of
CD11b + macrophages, with very few CD3+ T-lymphocytes. In contrast, T-lymphocytes
are more abundant in adult GBM tissue samples. RNA sequencing of macrophages
isolated from primary tumor samples revealed that DIPG- and adult GBM-associated
macrophages both express gene programs related to ECM remodeling and
angiogenesis, but DIPG-associated macrophages express substantially fewer
inflammatory factors than their adult GBM counterparts. Examining the secretome
of glioma cells, we found that patient-derived DIPG cell cultures secrete
markedly fewer cytokines and chemokines than patient-derived adult GBM cultures.
Concordantly, bulk and single-cell RNA sequencing data indicates low to absent
expression of chemokines and cytokines in DIPG. Together, these observations
suggest that the inflammatory milieu of the DIPG tumor microenvironment is
fundamentally different than adult GBM. The low intrinsic inflammatory signature
of DIPG cells may contribute to the lack of lymphocytes and non-inflammatory
phenotype of DIPG-associated microglia/macrophages. Understanding the glioma
subtype-specific inflammatory milieu may inform the design and application of
immunotherapy-based treatments.
PMID- 29954446
TI - The benefit of combinations of oximes for the ability of antidotal treatment to
counteract sarin-induced brain damage in rats.
AB - BACKGROUND: The aim of our study was to compare the ability of two combinations
of oximes (HI-6 + trimedoxime and HI-6 + K203) with atropine to counteract acute
sarin-induced brain damage with the efficacy of antidotal treatment involving
single oxime (HI-6) and atropin using in vivo methods. METHODS: Brain damage and
neuroprotective effects of antidotal treatment were evaluated in rats poisoned
with sarin at a sublethal dose (108 MUg/kg i.m.; 90% LD50) using
histopathological, Fluoro-Jade B and Terminal deoxynucleotidyl transferase dUTP
nick end labeling (TUNEL) analysis 24 h after sarin administration. RESULTS: Both
combinations of oximes reduce the number of rats that died before the end of
experiment compared to non-treated sarin poisoning and sarin poisoning treated
with HI-6 and atropine. In the case of treatment of sarin poisoning with HI-6 in
combination with K203, all rats survived till the end of experiment. HI-6 with
atropine was able to reduce sarin-induced brain damage, however, both
combinations were slightly more effective. CONCLUSIONS: The oxime HI-6 in
combination with K203 and atropine seems to be the most effective. Thus, both
tested oxime combinations bring a small benefit in elimination of acute sarin
induced brain damage compared to single oxime antidotal therapy.
PMID- 29954447
TI - Is the cross-over effect of a unilateral high-intensity leg extension influenced
by the sex of the participants?
AB - BACKGROUND: While performing a unilateral muscle contraction, electrical muscle
activity also arises in the contralateral homologous muscle, muscle group, or
limb. When the muscle contraction induces muscle fatigue, females show not only a
greater resistance than males but also a reduced contralateral muscle activation.
The study aimed at investigating whether, during a high-intensity 30-s unilateral
maximal effort isometric leg extension exercise, the contralateral non-exercising
limb (NEL) knee extensor muscle activation would differ between females and
males. METHODS: Twenty participants, 11 females (23.80 +/- 2.15 years old) and 9
males (26.50 +/- 2.45 years old), performed a unilateral 30-s exercise while
surface electromyography (sEMG) was measured from the vastus lateralis (VL),
vastus medialis (VM), and rectus femoris (RF) on both limbs. The maximal
voluntary contraction (MVC) was measured for both the exercising limb (EL) and
the NEL before (MVC PRE) and after (MVC POST) the 30-s exercise to assess muscle
fatigue. RESULTS: While both females and males exhibited muscle fatigue in the EL
(p = 0.015), females exhibited a lower MVC reduction than males (p = 0.042),
suggesting that females were less fatigued than males. Although no muscle
fatigue, i.e., no MVC force reduction was found in the NEL for either group
before and after the 30-s exercise, the muscle activity of the VL was found to be
of greater magnitude during the MVC POST only for females (p = 0.047) while it
remained unchanged for males. During the 30-s exercise, the force output of the
EL decreased only for males (p = 0.029) while females showed a preservation of
the force output (p > 0.05). The sEMG activity of the NEL during the 30-s
unilateral exercise increased for both groups in all measured muscles (all p
values < 0.03). CONCLUSIONS: Likely, different underlying muscle fatigue
mechanisms occurred in the EL between females and males. Yet, our findings
suggest that the cross-over effect to the NEL during the 30-s exercise occurred
in a similar fashion in both groups. The current study suggests that the
contralateral muscle activation seen with a unilateral exercise is independent of
the sex of individuals. Therefore, unilateral training or rehabilitation-based
protocols would similarly impact females and males.
PMID- 29954448
TI - Increased richness and diversity of the vaginal microbiota and spontaneous
preterm birth.
AB - BACKGROUND: The bacterial community present in the female lower genital tract
plays an important role in maternal and neonatal health. Imbalances in this
microbiota have been associated with negative reproductive outcomes, such as
spontaneous preterm birth (sPTB), but the mechanisms underlying the association
between a disturbed microbiota and sPTB remain poorly understood. An intrauterine
infection ascending from the vagina is thought to be an important contributor to
the onset of preterm labour. Our objective was to characterize the vaginal
microbiota of pregnant women who had sPTB (n = 46) and compare to those of
pregnant women who delivered at term (n = 170). Vaginal swabs were collected from
women at 11-16 weeks of gestational age. Microbiota profiles were created by PCR
amplification and pyrosequencing of the cpn60 universal target region. RESULTS:
Profiles clustered into seven community state types: I (Lactobacillus crispatus
dominated), II (Lactobacillus gasseri dominated), III (Lactobacillus iners
dominated), IVA (Gardnerella vaginalis subgroup B or mix of species), IVC (G.
vaginalis subgroup A dominated), IVD (G. vaginalis subgroup C dominated) and V
(Lactobacillus jensenii dominated). The microbiota of women who experienced
preterm birth (< 37 weeks gestation) had higher richness and diversity and higher
Mollicutes prevalence when compared to those of women who delivered at term. The
two groups did not cluster according to CST, likely because CST assignment is
driven in most cases by the dominance of one particular species, overwhelming the
contributions of more rare taxa. In conclusion, we did not identify a specific
microbial community structure that predicts sPTB, but differences in microbiota
richness, diversity and Mollicutes prevalence were observed between groups.
CONCLUSIONS: Although a causal relationship remains to be determined, our results
confirm previous reports of an association between Mollicutes and sPTB and
further suggest that a more diverse microbiome may be important in the
pathogenesis of some cases.
PMID- 29954449
TI - Long-term weight loss trajectories following participation in a randomised
controlled trial of a weight management programme for men delivered through
professional football clubs: a longitudinal cohort study and economic evaluation.
AB - BACKGROUND: Obesity is a major public health concern requiring innovative
interventions that support people to lose weight and keep it off long term.
However, weight loss maintenance remains a challenge and is under-researched,
particularly in men. The Football Fans in Training (FFIT) programme engages men
in weight management through their interest in football, and encourages them to
incorporate small, incremental physical activity and dietary changes into daily
life to support long-term weight loss maintenance. In 2011/12, a randomised
controlled trial (RCT) of FFIT demonstrated effectiveness and cost-effectiveness
at 12 months. The current study aimed to investigate long-term maintenance of
weight loss, behavioural outcomes and lifetime cost-effectiveness following FFIT.
METHODS: A longitudinal cohort study comprised 3.5-year follow-up of the 747 FFIT
RCT participants. Men aged 35-65 years, BMI >= 28 kg/m2 at RCT baseline who
consented to long-term follow-up (n = 665) were invited to participate: those in
the FFIT Follow Up Intervention group (FFIT-FU-I) undertook FFIT in 2011 during
the RCT; the FFIT Follow Up Comparison group (FFIT-FU-C) undertook FFIT in 2012
under routine (non-research) conditions. The primary outcome was objectively
measured weight loss (from baseline) at 3.5 years. Secondary outcomes included
changes in self-reported physical activity and diet at 3.5 years. Cost
effectiveness was estimated at 3.5 years and over participants' lifetime.
RESULTS: Of 665 men invited, 488 (73%; 65% of the 747 RCT participants) attended
3.5-year measurements. The FFIT-FU-I group sustained a mean weight loss of 2.90
kg (95% CI 1.78, 4.02; p < 0.001) 3.5 years after starting FFIT; 32.2% (75/233)
weighed >=5% less than baseline. The FFIT-FU-C group had lost 2.71 kg (1.65,
3.77; p < 0.001) at the 3.5-year measurements (2.5 years after starting FFIT);
31.8% (81/255) weighed >=5% less than baseline. There were significant sustained
improvements in self-reported physical activity and diet in both groups. The
estimated incremental cost-effectiveness of FFIT was L10,700-L15,300 per QALY
gained at 3.5 years, and L1790-L2200 over participants' lifetime. CONCLUSIONS:
Participation in FFIT under research and routine conditions leads to long-term
weight loss and improvements in physical activity and diet. Investment in FFIT is
likely to be cost-effective as part of obesity management strategies in countries
where football is popular. TRIAL REGISTRATION: ISRCTN32677491 , 20 October 2011.
PMID- 29954450
TI - Prevalence of needle stick injury and its associated factors among nurses working
in public hospitals of Dessie town, Northeast Ethiopia, 2016.
AB - OBJECTIVE: Nurses are exposed to dangerous and deadly blood borne pathogens
through contaminated needle stick injuries. This study was designed to assess
prevalence of needle stick injury and its associated factors among nurses working
in hospitals. Institution-based cross-sectional study design was used among 258
randomly selected nurses. Collected data was entered into Epi-Data version 3.1
and transferred to SPSS Version 20.0 for analysis. The degree of variables were
assessed using adjusted odds ratio and its 95% confidence interval with P value
(< 0.05). RESULTS: Eighty-nine (34.5%) nurses self-reported receiving a needle
stick injury in the previous 12 months. Work experience, working hour, personal
protective, infection prevention guide line utilization and infection prevention
training were significantly associated to needle stick injury. CONCLUSIONS: The
needle stick injury in this study area was prevalent. The contributing factors to
the injury were duration of working hours, experience, use of personal protective
equipment and training.
PMID- 29954451
TI - Tuberculosis co-infection and its associated factors among People living with
HIV/AIDS attending antiretroviral therapy clinic in southern Ethiopia: a facility
based retrospective study.
AB - OBJECTIVE: The study aimed to determine the prevalence and identify determinants
of TB among People living with HIV/AIDS (PLWHAs) through reviewing and analyzing
patient case files from the anti-retro viral treatment (ART) clinic of Yirgalem
General Hospital, southern Ethiopia. RESULTS: Of the total PLWHAs involved in the
study, 51 (36.9%) of them were found to have TB, and of which, 37 (72.5%) were
smear negative cases. The multivariate analysis showed that PLWHA's who are at
WHO clinical stage 3 (AOR = 5.82; 95% CI 1.04-32.30), CD4 level of 200-500
cells/mm3 (AOR = 4.85; 95% CI 1.95-12.05) and < 200 cells/mm3 (AOR = 7.34; 95% CI
2.75-19.58) at ART initiation, and who didn't take INH prophylaxis (AOR = 12.36;
95% CI 4.47-34.14) were significantly associated with TB-HIV co-infection. Rapid
and sensitive diagnostic techniques should be implemented to early detect co
infections, and also INH prophylactic preventive measures should be strengthened
to reduce TB incidence.
PMID- 29954452
TI - Red blood cell indices and anaemia as causative factors for cognitive function
deficits and for Alzheimer's disease.
AB - BACKGROUND: Studies have shown that low haemoglobin and anaemia are associated
with poor cognition, and anaemia is known to be associated with Alzheimer's
disease (AD), but the mechanism of this risk is unknown. Here, we first seek to
confirm the association between cognition and anaemia and secondly, in order to
further understand the mechanism of this association, to estimate the direction
of causation using Mendelian randomisation. METHODS: Two independent cohorts were
used in this analysis: AddNeuroMed, a longitudinal study of 738 subjects
including AD and age-matched controls with blood cell measures, cognitive
assessments and gene expression data from blood; and UK Biobank, a study of
502,649 healthy participants, aged 40-69 years with cognitive test measures and
blood cell indices at baseline. General linear models were calculated using
cognitive function as the outcome with correction for age, sex and education. In
UK Biobank, SNPs with known blood cell measure associations were analysed with
Mendelian randomisation to estimate direction of causality. In AddNeuroMed, gene
expression data was used in pathway enrichment analysis to identify associations
reflecting biological function. RESULTS: Both sample sets evidence a reproducible
association between cognitive performance and mean corpuscular haemoglobin (MCH),
a measure of average mass of haemoglobin per red blood cell. Furthermore, in the
AddNeuroMed cohort, where longitudinal samples were available, we showed a
greater decline in red blood cell indices for AD patients when compared to
controls (p values between 0.05 and 10-6). In the UK Biobank cohort, we found
lower haemoglobin in participants with reduced cognitive function. There was a
significant association for MCH and red blood cell distribution width (RDW, a
measure of cell volume variability) compared to four cognitive function tests
including reaction time and reasoning (p < 0.0001). Using Mendelian
randomisation, we then showed a significant effect of MCH on the verbal-numeric
and numeric traits, implying that anaemia has causative effect on cognitive
performance. CONCLUSIONS: Lower haemoglobin levels in blood are associated to
poor cognitive function and AD. We have used UK Biobank SNP data to determine the
relationship between cognitive testing and haemoglobin measures and suggest that
haemoglobin level and therefore anaemia does have a primary causal impact on
cognitive performance.
PMID- 29954453
TI - Evaluation of bias induced by viral enrichment and random amplification protocols
in metagenomic surveys of saliva DNA viruses.
AB - BACKGROUND: Viruses are key players regulating microbial ecosystems. Exploration
of viral assemblages is now possible thanks to the development of metagenomics,
the most powerful tool available for studying viral ecology and discovering new
viruses. Unfortunately, several sources of bias lead to the misrepresentation of
certain viruses within metagenomics workflows, hindering the shift from merely
descriptive studies towards quantitative comparisons of communities. Therefore,
benchmark studies on virus enrichment and random amplification protocols are
required to better understand the sources of bias. RESULTS: We assessed the bias
introduced by viral enrichment on mock assemblages composed of seven DNA viruses,
and the bias from random amplification methods on human saliva DNA viromes, using
qPCR and deep sequencing, respectively. While iodixanol cushions and 0.45 MUm
filtration preserved the original composition of nuclease-protected viral
genomes, low-force centrifugation and 0.22 MUm filtration removed large viruses.
Comparison of unamplified and randomly amplified saliva viromes revealed that
multiple displacement amplification (MDA) induced stochastic bias from picograms
of DNA template. However, the type of bias shifted to systematic using 1 ng, with
only a marginal influence by amplification time. Systematic bias consisted of
over-amplification of small circular genomes, and under-amplification of those
with extreme GC content, a negative bias that was shared with the PCR-based
sequence-independent, single-primer amplification (SISPA) method. MDA based on
random priming provided by a DNA primase activity slightly outperformed those
based on random hexamers and SISPA, which may reflect differences in ability to
handle sequences with extreme GC content. SISPA viromes showed uneven coverage
profiles, with high coverage peaks in regions with low linguistic sequence
complexity. Despite misrepresentation of certain viruses after random
amplification, ordination plots based on dissimilarities among contig profiles
showed perfect overlapping of related amplified and unamplified saliva viromes
and strong separation from unrelated saliva viromes. This result suggests that
random amplification bias has a minor impact on beta diversity studies.
CONCLUSIONS: Benchmark analyses of mock and natural communities of viruses
improve understanding and mitigate bias in metagenomics surveys. Bias induced by
random amplification methods has only a minor impact on beta diversity studies of
human saliva viromes.
PMID- 29954455
TI - Chondroid lipoma of the neck: a case report.
AB - BACKGROUND: Chondroid lipoma, first described in 1993 by Meis and Enzinger, is a
very rare lipomatous tumor. Because it is a benign tumor, it does not require
radiotherapy, chemotherapy, or extensive resection. However, histologically, it
is often confused with a sarcoma. It is crucial to differentiate chondroid lipoma
from sarcoma to avoid choosing an inappropriate treatment strategy. Although MRI,
radiography, and ultrasound have been used to evaluate chondroid lipomas, imaging
cannot accurately differentiate chondroid lipoma from sarcoma. CASE PRESENTATION:
A 39-year-old man presented to a local clinic with a 1-month history of a
painless mass in his left neck. Results of a needle biopsy suggested an atypical
lipomatous tumor, and the patient was referred to our hospital. Physical
examination revealed a hard and mobile mass in the left neck. Plain X-ray
radiographs showed an absence of calcification in the soft tissue mass. MRI
revealed a well-defined and lobulated mass, and on T1-weighted images, the lesion
showed heterogeneity, with higher signal intensity than that of muscle. On T2
weighted images, the septum had low-signal intensity. On T2-weighted fat
suppressed images, the signal of the mass was completely suppressed. The SUVmax
of the mass on FDG PET was 1.84. An additional needle biopsy was performed, and
on the basis of the results, we arrived at a diagnosis of well-differentiated
liposarcoma. The mass was resected marginally. Macroscopically, the mass was
encapsulated and markedly harder than well-differentiated liposarcoma.
Histologically, the tumor was composed of myxoid and cartilaginous matrix, and
mature fat cells and lipoblast-like cells were present. The final diagnosis was
chondroid lipoma, and no recurrence was observed 1 year after surgery.
CONCLUSIONS: Chondroid lipoma is an extremely rare benign soft tissue tumor that
is often confused with sarcoma. It is very important to differentiate chondroid
lipoma from sarcoma when the SUVmax value of the mass is low, even when biopsy
results suggest that it is a sarcoma.
PMID- 29954454
TI - Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal
barrier function in obese adults but show no synergism when used together as
synbiotics.
AB - BACKGROUND: One way to improve both the ecological performance and functionality
of probiotic bacteria is by combining them with a prebiotic in the form of a
synbiotic. However, the degree to which such synbiotic formulations improve
probiotic strain functionality in humans has not been tested systematically. Our
goal was to use a randomized, double-blind, placebo-controlled, parallel-arm
clinical trial in obese humans to compare the ecological and physiological impact
of the prebiotic galactooligosaccharides (GOS) and the probiotic strains
Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo
selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous
to the human gut) when used on their own or as synbiotic combinations. After 3
weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA
gene sequencing were performed on fecal samples to assess changes in the
microbiota. Intestinal permeability was determined by measuring sugar recovery in
urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure
was also assessed. RESULTS: IVS-1 reached significantly higher cell numbers in
fecal samples than BB-12 (P < 0.01) and, remarkably, its administration induced
an increase in total bifidobacteria that was comparable to that of GOS. Although
GOS showed a clear bifidogenic effect on the resident gut microbiota, both
probiotic strains showed only a non-significant trend of higher fecal cell
numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were
reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P =
0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P =
0.020), indicating improvements in colonic permeability but no synergistic
effects. No changes in markers of endotoxemia were observed. CONCLUSION: This
study demonstrated that "autochthony" of the probiotic strain has a larger effect
on ecological performance than the provision of a prebiotic substrate, likely due
to competitive interactions with members of the resident microbiota. Although the
synbiotic combinations tested in this study did not demonstrate functional
synergism, our findings clearly showed that the pro- and prebiotic components by
themselves improved markers of colonic permeability, providing a rational for
their use in pathologies with an underlying leakiness of the gut.
PMID- 29954456
TI - The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a
post-transcriptional level.
AB - BACKGROUND: The ability of human immunodeficiency virus type 1 (HIV-1) to form a
stable viral reservoir is the major obstacle to an HIV-1 cure and post
transcriptional events contribute to the maintenance of viral latency. RNA
surveillance proteins such as UPF1, UPF2 and SMG6 affect RNA stability and
metabolism. In our previous work, we demonstrated that UPF1 stabilises HIV-1
genomic RNA (vRNA) and enhances its translatability in the cytoplasm. Thus, in
this work we evaluated the influence of RNA surveillance proteins on vRNA
expression and, as a consequence, viral reactivation in cells of the lymphoid
lineage. METHODS: Quantitative fluorescence in situ hybridisation-flow cytometry
(FISH-flow), si/shRNA-mediated depletions and Western blotting were used to
characterise the roles of RNA surveillance proteins on HIV-1 reactivation in a
latently infected model T cell line and primary CD4+ T cells. RESULTS: UPF1 was
found to be a positive regulator of viral reactivation, with a depletion of UPF1
resulting in impaired vRNA expression and viral reactivation. UPF1 overexpression
also modestly enhanced vRNA expression and its ATPase activity and N-terminal
domain were necessary for this effect. UPF2 and SMG6 were found to negatively
influence viral reactivation, both via an interaction with UPF1. UPF1 knockdown
also resulted in reduced vRNA levels and viral gene expression in HIV-1-infected
primary CD4+ T cells. CONCLUSION: Overall, these data suggest that RNA
surveillance proteins affect HIV-1 gene expression at a post-transcriptional
level. An elucidation of the role of vRNA metabolism on the maintenance of HIV-1
persistence can lead to the development of novel curative strategies.
PMID- 29954458
TI - Tension band plating of an anterior tibial stress fracture nonunion in an elite
athlete, initially treated with intramedullary nailing: a case report.
AB - BACKGROUND: Leg pain in athletes is a common condition and is often related to
tibial stress fracture. When non-operative treatment fails, the optimal surgical
treatment is controversial. The aim of this study was to report a case of tension
band plating of an anterior tibial stress fracture nonunion, treated previously
with intramedullary nailing. To the best of our knowledge, this is the first
reported case in which tension band plating was placed without removing the
preexisting intramedullary nail. CASE PRESENTATION: The tibial shaft is a common
location of stress fracture in athletes. Anterior tibial stress fractures are
difficult to manage. When conservative treatment fails, intramedullary nailing is
the mainstay of treatment. However, nonunion is a serious complication. In our
case, a non-united anterior tibial stress fracture, treated with intramedullary
nailing, was addressed with the application of a compression prebended plate over
the nail in a 23-year-old French man of African origin who is an elite football
player. At 3-months postoperatively he was pain free and started light exercises.
At 6-months postoperatively, complete radiologic union of the fracture was
evident. He was symptom free; he resumed at that time a full training program and
he returned to play football at preinjury high competition level. CONCLUSIONS:
Compression plating is a valuable method of treating non-united anterior tibial
stress fractures. We believe that anterior tension band plating is superior to
intramedullary nailing in managing anterior tibial stress fractures, not only
after failure of intramedullary nailing, but also as a first-line surgical
treatment. This technique offers advantages, such as no violation of the extensor
mechanism and risk of anterior knee pain, and directly addresses the underlying
problem of distraction forces acting on the anterior tibial cortex and
compromising fracture healing. Especially in high-level athletes, who cannot
tolerate prolonged inactivity, early surgical intervention of anterior tibial
stress fractures with tension band plating is a reliable option that can
accelerate recovery.
PMID- 29954459
TI - Identification of cyclic hexapeptides natural products with inhibitory potency
against Mycobacterium tuberculosis.
AB - OBJECTIVE: Our aim was to identify natural products with anti-tubercular
activity. RESULTS: A set of ~ 500 purified natural product compounds was screened
for inhibition against the human pathogen Mycobacterium tuberculosis. A series of
cyclic hexapeptides with anti-tubercular activity was identified. Five analogs
from a set of sixteen closely related compounds were active, with minimum
inhibitory concentrations ranging from 2.3 to 8.9 MUM. Eleven structural analogs
had no significant activity (MIC > 20 MUM) demonstrating structure activity
relationship. Sequencing of resistant mutant isolates failed to identify changes
accounting for the resistance phenotype.
PMID- 29954457
TI - Human mesenchymal stem cell-derived extracellular vesicles/estrogen combined
therapy safely ameliorates experimentally induced intrauterine adhesions in a
female rat model.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) have diverse functions in regulating
injury and inflammation through the secretion of extracellular vesicles (EVs).
METHODS: In this study, we investigated the systemic administration of
extracellular vesicles derived from human umbilical cord mesenchymal stem cells
(UCMSCs-EVs) as a therapeutic agent for intrauterine adhesions (IUAs) caused by
endometrial injury. Additionally, we investigated the therapeutic impact of both
UCMSCs-EVs and estrogen either separately or in combination in a rat model. The
inflammation, vascularization, proliferation, and extent of fibrosis were
assessed by a histopathological and immunohistochemical assessment using
transforming growth factor (TGF)-beta as a fibrotic marker and vascular
endothelial growth factor (VEGF) as a vascular marker. Additionally, quantitative
real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression
of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6 (inflammatory
cytokines), CD140b (a marker of endometrial stem cells), and RUNX2 (an
antifibrotic factor). Finally, Western blotting was used to evaluate collagen I
and beta-actin expression. RESULTS: The therapeutic groups treated with either
UCMSCs-EVs alone or combined with estrogen exhibited a significant decrease in
inflammation and fibrosis (TNF-alpha, TGF-beta, IL-1, IL-6, RUNX2, and collagen
I) as well as a significant decrease in vascularization (VEGF) compared with the
untreated rats with IUAs. The most significant results were obtained in animals
with IUAs that received a combined therapy of UCMSCs-EVs and estrogen.
CONCLUSIONS: We conclude that the synergistic action of human UCMSCs-EVs combined
with estrogen provides a highly effective alternative regenerative agent in IUA
treatment.
PMID- 29954460
TI - Facultative methanotrophs are abundant at terrestrial natural gas seeps.
AB - BACKGROUND: Natural gas contains methane and the gaseous alkanes ethane, propane
and butane, which collectively influence atmospheric chemistry and cause global
warming. Methane-oxidising bacteria, methanotrophs, are crucial in mitigating
emissions of methane as they oxidise most of the methane produced in soils and
the subsurface before it reaches the atmosphere. Methanotrophs are usually
obligate, i.e. grow only on methane and not on longer chain alkanes. Bacteria
that grow on the other gaseous alkanes in natural gas such as propane have also
been characterised, but they do not grow on methane. Recently, it was shown that
the facultative methanotroph Methylocella silvestris grew on ethane and propane,
other components of natural gas, in addition to methane. Therefore, we
hypothesised that Methylocella may be prevalent at natural gas seeps and might
play a major role in consuming all components of this potent greenhouse gas
mixture before it is released to the atmosphere. RESULTS: Environments known to
be exposed to biogenic methane emissions or thermogenic natural gas seeps were
surveyed for methanotrophs. 16S rRNA gene amplicon sequencing revealed that
Methylocella were the most abundant methanotrophs in natural gas seep
environments. New Methylocella-specific molecular tools targeting mmoX (encoding
the soluble methane monooxygenase) by PCR and Illumina amplicon sequencing were
designed and used to investigate various sites. Functional gene-based assays
confirmed that Methylocella were present in all of the natural gas seep sites
tested here. This might be due to its ability to use methane and other short
chain alkane components of natural gas. We also observed the abundance of
Methylocella in other environments exposed to biogenic methane, suggesting that
Methylocella has been overlooked in the past as previous ecological studies of
methanotrophs often used pmoA (encoding the alpha subunit of particulate methane
monooxygenase) as a marker gene. CONCLUSION: New biomolecular tools designed in
this study have expanded our ability to detect, and our knowledge of the
environmental distribution of Methylocella, a unique facultative methanotroph.
This study has revealed that Methylocella are particularly abundant at natural
gas seeps and may play a significant role in biogeochemical cycling of gaseous
hydrocarbons.
PMID- 29954461
TI - Use of quantitative PCR to assess the efficacy of albendazole against Necator
americanus and Ascaris spp. in Manufahi District, Timor-Leste.
AB - BACKGROUND: Soil-transmitted helminths (STHs) including Ascaris lumbricoides,
Necator americanus, Ancylostoma spp. and Trichuris trichiura are cause of
significant global morbidity. To mitigate their disease burden, at-risk groups in
endemic regions receive periodic mass drug administration using anthelmintics,
most commonly albendazole and mebendazole. Assessing the efficacy of anthelmintic
drugs is important for confirming that these regimens are working effectively and
that drug resistance has not emerged. In this study we aimed to characterise the
therapeutic efficacy of albendazole against Ascaris spp. and N. americanus in
Timor-Leste, using a quantitative polymerase chain reaction (qPCR) method for
parasite detection and quantification. RESULTS: A total of 314 participants from
8 communities in Timor-Leste provided stool samples before and 10-14 days after
the administration of a single 400 mg dose of albendazole. Helminth infection
status and infection intensity (measured in Ct-values and relative fluorescence
units) were determined using qPCR. Efficacy was determined by examining the cure
rates and infection intensity reduction rates. Albendazole was found to be highly
efficacious against Ascaris spp., with a cure rate of 91.4% (95% CI: 85.9-95.2%)
and infection intensity reduction rate of 95.6% (95% CI: 88.3-100%). The drug was
less efficacious against N. americanus with a cure rate of 58.3% (95% CI: 51.4
64.9%) and infection intensity reduction rate of 88.9% (95% CI: 84.0-97.0%).
CONCLUSIONS: The observed cure rates and infection intensity reduction rates
obtained for Ascaris spp. and to a lower extent N. americanus, demonstrate the
continued efficacy of albendazole against these species and its utility as a mass
chemotherapy agent in Timor-Leste. Furthermore, this study demonstrates the
usefulness of qPCR as a method to measure the efficacy of anthelminthic drugs.
Additional research is necessary to translate Ct-values into eggs per gram in a
systematic way. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials
Registry 12614000680662 (registered 27 June 2014).
PMID- 29954463
TI - Patent ductus arteriosus in preterm infants born before 30 weeks' gestation: high
rate of spontaneous closure after hospital discharge.
AB - : AimThe aim of this study was to determine the spontaneous closure rate of
patent ductus arteriosus at a 2-year follow-up, following failed medical therapy
and beyond initial hospital discharge, and to evaluate in-hospital spontaneous or
pharmacological closure rates.Materials and methodsA retrospective evaluation was
conducted in a cohort of preterm infants admitted to the Neonatal ICU of Ancona
between January, 2004 and June, 2013. Inclusion criteria were gestational age
between 24+0 and 29+6 weeks or birth weight 1.5 mm, a left atrium-to-aorta ratio
>1.4, and/or reversal of end-diastolic flow in the aorta >30% of the anterograde.
First-line treatment was intravenous ibuprofen. Intravenous indomethacin was used
if ibuprofen failed. Surgical ligation was considered in haemodynamically
significant patent ductus arteriosus after medical treatment. RESULTS: A total of
593 infants met the inclusion criteria, and patent ductus arteriosus was
diagnosed in 317 (53.4%). Among them, 283 (89.3%) infants had haemodynamically
significant patent ductus arteriosus, with pharmacological closure achieved in
228 (80.6%) infants and surgical ligation performed in 20 (7.1%). Follow-up at 24
months was available for 39 (81.3%) of 48 infants with patent ductus arteriosus
at the hospital discharge: 36 (92.3%) underwent spontaneous closure, two (5.1%)
underwent surgical ligation, and one (2.6%) had a patent ductus
arteriosus.DiscussionA significant number of patent ductus arteriosus that fail
pharmacological closure undergo spontaneous closure by the age of 2 years. This
information should be taken into account when considering surgery or additional
attempts of pharmacological closure.
PMID- 29954462
TI - New operational taxonomic units of Enterocytozoon in three marsupial species.
AB - BACKGROUND: Enterocytozoon bieneusi is a microsporidian, commonly found in
animals, including humans, in various countries. However, there is scant
information about this microorganism in Australasia. In the present study, we
conducted the first molecular epidemiological investigation of E. bieneusi in
three species of marsupials (Macropus giganteus, Vombatus ursinus and Wallabia
bicolor) living in the catchment regions which supply the city of Melbourne with
drinking water. METHODS: Genomic DNAs were extracted from 1365 individual faecal
deposits from these marsupials, including common wombat (n = 315), eastern grey
kangaroo (n = 647) and swamp wallaby (n = 403) from 11 catchment areas, and then
individually tested using a nested PCR-based sequencing approach employing the
internal transcribed spacer (ITS) and small subunit (SSU) of nuclear ribosomal
DNA as genetic markers. RESULTS: Enterocytozoon bieneusi was detected in 19 of
the 1365 faecal samples (1.39%) from wombat (n = 1), kangaroos (n = 13) and
wallabies (n = 5). The analysis of ITS sequence data revealed a known (designated
NCF2) and four new (MWC_m1 to MWC_m4) genotypes of E. bieneusi. Phylogenetic
analysis of ITS sequence data sets showed that MWC_m1 (from wombat) clustered
with NCF2, whereas genotypes MWC_m2 (kangaroo and wallaby), MWC_m3 (wallaby) and
MWC_m4 (kangaroo) formed a new, divergent clade. Phylogenetic analysis of SSU
sequence data revealed that genotypes MWC_m3 and MWC_m4 formed a clade that was
distinct from E. bieneusi. The genetic distinctiveness of these two genotypes
suggests that they represent a new species of Enterocytozoon. CONCLUSIONS:
Further investigations of Enterocytozoon spp. from macropods and other animals
will assist in clarifying the taxonomy and epidemiology of these species in
Australia and elsewhere, and in assessing the public health risk of
enterocytozoonosis.
PMID- 29954464
TI - Comparison of cognitive functions among frail and prefrail older adults: a
clinical perspective.
AB - : ABSTRACTObjective:To compare cognitive function among frail and prefrail older
adults. DESIGN: Cross-sectional clinical study. PARTICIPANTS: Fifty-one non
institutionalized older individuals participated in this study. MEASUREMENTS:
Cognitive functions were evaluated through Mini-Mental State Examination (Global
Cognition), Digit Span Forward (short-term memory), Digit Span Backward (working
memory), Verbal Fluency Test (semantic memory/executive function). Data were
compared using parametric and non-parametric bivariate tests. Binary logistic
regression was used to test a frailty prediction model. Statistical significance
was defined as p <= 0.01 to compare groups. In the regression model, the p value
was set to be <=0.05. RESULTS: Statistically significant differences were
observed in global cognition, and short-term memory between frail and prefrail
individuals (p <= 0.01). Global cognition explained 14-19% of frailty's model.
CONCLUSION: According to our findings, the evaluation of cognitive functions
among older persons with frailty and prefrailty provides important complementary
information to better manage frailty and its progression.
PMID- 29954466
TI - Antibiotic-induced alterations of the gut microbiota and microbial fermentation
in protein parallel the changes in host nitrogen metabolism of growing pigs.
AB - Gut microbes, especially those in the large intestine, are actively involved in
nutrient metabolism; however, their impact on host nitrogen (N) metabolism
remains largely unknown. This study was designed to investigate the effects of
feeding a cocktail of antibiotics (AGM) (ampicillin, gentamycin and
metronidazole) on intestinal microbiota, N utilization efficiency, and amino acid
(AA) digestibility in cannulated pigs, with the aim of exploring the impact of
gut microbiota on host N metabolism. In total, 16 piglets were surgically fitted
with a simple distal ileal T-cannula and a jugular venous catheter. The pigs were
fed a basal diet without antibiotics (control; CON) or with antibiotics
(antibiotic; ANTI), for 2 weeks. The results showed that feeding AGM did not
affect weight gain or digestive enzyme activity. The antibiotics increased the
concentration of urea N (P<0.05). However, they reduced N utilization, and the
total tract apparent digestibility of isoleucine, methionine, valine, tyrosine
and total AA (P<0.05). Furthermore, the antibiotics increased the terminal ileum
apparent digestibility of CP, phenylalanine, valine, alanine, tyrosine and total
AA (P<0.05). AGM markedly altered the composition of the microbiota in the ileum
and feces, with a reduction in populations of Bifidobacterium, Lactobacillus and
Ruminococcus, and an increase in the abundance of Escherichia coli (P<0.05). The
antibiotics also significantly increased the concentration of cadaverine and
ammonia, both in ileal digesta and feces (P<0.05), suggesting a marked impact on
N metabolism in the intestine. The analyses indicated that the alteration of gut
microbiota was correlated with the apparent digestibility of CP and AA in the
intestine. These findings suggest that the AGM-induced alteration of gut
microbiota may contribute to the change in intestinal N metabolism, and
consequently, N excretion from the body. These results also suggest that
antibiotics could have a significant effect on host N metabolism. The present
study contributes to our understanding of the effects of antibiotics and provides
a rational scientific basis for diet formulation during AGM use.
PMID- 29954465
TI - Functional Brain Alterations Associated With Cognitive Control in Blast-Related
Mild Traumatic Brain Injury.
AB - OBJECTIVES: Research on the cognitive sequelae of mild traumatic brain injury
(mTBI) suggests that, despite generally rapid recovery, difficulties may persist
in the domain of cognitive control. The goal of this study was to examine whether
individuals with chronic blast-related mTBI show behavioral or neural alterations
associated with cognitive control. METHODS: We collected event-related functional
magnetic resonance imaging (fMRI) data during a flanker task in 17 individuals
with blast-related mTBI and 16 individuals with blast-exposure without TBI
(control). RESULTS: Groups did not significantly differ in behavioral measures of
cognitive control. Relative to the control group, the mTBI group showed greater
deactivation of regions associated with the default mode network during the
processing of errors. Additionally, error processing in the mTBI group was
associated with enhanced negative coupling between the default mode network and
the dorsal anterior cingulate cortex as well as the dorsolateral prefrontal
cortex, regions of the salience and central executive networks that are
associated with cognitive control. CONCLUSIONS: These results suggest that
deactivation of default mode network regions and associated enhancements of
connectivity with cognitive control regions may act as a compensatory mechanism
for successful cognitive control task performance in mTBI. (JINS, 2018, 24, 662
672).
PMID- 29954467
TI - Estimates of genetic parameters and genetic trends for growth, reproduction, milk
production and milk composition traits of Awassi sheep.
AB - Genetic parameters and genetic trends for growth, reproduction, milk production
and composition traits were estimated for Syrian (S) and Turkish (T) Awassi sheep
and their crosses maintained at the International Center for Agricultural
Research in the Dry Areas Tal Hadya station, Aleppo, Syria (now in Terbol station
in Lebanon). The data were spread over 9 years. The individual breed additive
effects of T were positive and significant (P0.05) for most growth traits.
Crossing of T with S, however, resulted in desirable and significant (P<0.05)
individual heterosis effects for all the reproduction, milk production and
constituent yields. The heritability (h2) estimates, both direct and maternal,
were low for BW, WW, WG and all reproductive traits indicating major influence of
environmental factors, whereas milk yield and composition had medium values.
Birth weight had moderate genetic correlation with WW and WG. The genetic
correlation between WW and WG was high (0.724+/-0.951). Lambing interval had
large negative genetic correlation with LWB and LWW. However, LI had medium
significant correlations with all the milk production and composition traits.
Larger litter weights at birth had high and negative influence on milk yield of
the dam and its constituents. Genetic changes over years for all traits were non
significant. The lack of genetic change in the studied traits calls for
systematic and organized selection scheme.
PMID- 29954468
TI - Effects of the inclusion of Moringa oleifera seed on rumen fermentation and
methane production in a beef cattle diet using the rumen simulation technique
(Rusitec).
AB - Moringa oleifera seeds are currently being used as a livestock feed across
tropical regions of the world due to its availability and palatability. However,
limited knowledge exists on the effects of the raw seeds on ruminant metabolism.
As such, the rumen stimulation technique was used to evaluate the effects of
substituting increasing concentrations of ground Moringa seeds (0, 100, 200 and
400 g/kg concentrate dry matter (DM)) in the diet on rumen fermentation and
methane production. Two identical, Rusitec apparatuses, each with eight
fermenters were used with the first 8 days used for adaptation and days 9 to 16
used for measurements. Fermenters were fed a total mixed ration with Urochloa
brizantha as the forage. Disappearance of DM, CP, NDF and ADF linearly decreased
(P<0.01) with increasing concentrations of Moringa seeds in the diet. Total
volatile fatty acid production and the acetate to propionate ratio were also
linearly decreased (P<0.01). However, only the 400 g/kg (concentrate DM basis)
treatment differed (P<0.01) from the control. Methane production (%), total
microbial incorporation of 15N and total production of microbial N linearly
decreased (P<0.01) as the inclusion of Moringa seeds increased. Though the
inclusion of Moringa seeds in the diet decreased CH4 production, this arose from
an unfavourable decrease in diet digestibility and rumen fermentation parameters.
PMID- 29954469
TI - Transmission routes of influenza A(H1N1)pdm09: analyses of inflight outbreaks.
AB - Knowledge about the infection transmission routes is significant for developing
effective intervention strategies. We searched the PubMed databases and
identified 10 studies with 14 possible inflight influenza A(H1N1)pdm09 outbreaks.
Considering the different mechanisms of the large-droplet and airborne routes, a
meta-analysis of the outbreak data was carried out to study the difference in
attack rates for passengers within and beyond two rows of the index case(s). We
also explored the relationship between the attack rates and the flight duration
and/or total infectivity of the index case(s). The risk ratios for passengers
seated within and beyond the two rows of the index cases were 1.7 (95% confidence
interval (CI) 0.98-2.84) for syndromic secondary cases and 4.3 (95% CI 1.25
14.54) for laboratory-confirmed secondary cases. Furthermore, with an increase of
the product of the flight duration and the total infectivity of the index cases,
the overall attack rate increased linearly. The study indicates that influenza
A(H1N1)pdm09 may mainly be transmitted via the airborne route during air travel.
A standardised approach for the reporting of such inflight outbreak
investigations would help to provide more convincing evidence for such inflight
transmission events.
PMID- 29954470
TI - Mountain pasturing of rearing stock reduces the culling risk as dairy cows.
AB - Alpine transhumance or droving livestock to mountainous areas during summer
months is highly relevant for Austrian agriculture but also for other countries
in Alpine regions. Access of rearing stock to mountain pastures is often claimed
to be beneficial with respect to health and longevity, but the robust evidence is
scarce. Therefore, its effect was tested by including it in the routine genetic
evaluation data set for longevity. Alpine transhumance records from 2004 to 2013
were used. After several plausibility checks and restriction to animals with sire
and dam known, records of 871 287 dual-purpose Fleckvieh cows sired by 9953 bulls
were available. Data were analysed by means of survival analysis accounting for
the time-dependent fixed effects of region-year-season, relative performance
within herd, change of herd size, and Alpine pasturing of cows, the fixed effects
age at first calving and Alpine pasturing of rearing stock, the random time
dependent effect of herd-year and the random genetic effects of sire and maternal
grandsire. Fleckvieh cows that had access to Alpine pasture during their rearing
period at least once for a minimum of 60 days had functional longevity that was
nearly 2 months prolonged compared with cows that had always stayed on the farms
as calves or heifers. In a more detailed analysis, the lowest relative culling
risk among the significant estimates was observed for cows that had been Alpine
pastured in years 1 and 3; it was about 15% below that of cows that never had
access to mountain grazing. Evidence for the beneficial effect of Alpine
pasturing of rearing stock on the animals' later fitness, indicated by longevity,
could thus be provided.
PMID- 29954471
TI - Genetic parameters for endocrine and traditional fertility traits, hyperketonemia
and milk yield in dairy cattle.
AB - High-yielding cows may suffer from negative energy balance during early
lactation, which can lead to ketosis and delayed ability of returning to
cyclicity after calving. Fast recovery after calving is essential when breeding
for improved fertility. Traditionally used fertility traits, such as the interval
from calving to first insemination (CFI), have low heritabilities and are highly
influenced by management decisions. Herd NavigatorTM management program samples
and analyses milk progesterone and beta-hydroxybutyrate (BHB) automatically
during milking. In this study, the genetic parameters of endocrine fertility
traits (measured from milk progesterone) and hyperketonemia (measured from milk
BHB) in early lactation were evaluated and compared with traditional fertility
traits (CFI, interval from calving to the last insemination and interval from
first to last insemination) and the milk yield in red dairy cattle herds in
Finland. Data included observations from 14 farms from 2014 to 2017. Data were
analyzed with linear animal models using DMU software and analyses were done for
first parity cows. Heritability estimates for traditional fertility traits were
low and varied between 0.03 and 0.07. Estimated heritabilities for endocrine
fertility traits (interval from calving to the first heat (CFH) and commencement
of luteal activity (C-LA)) were higher than for traditional fertility traits
(0.19 to 0.33). Five slightly different hyperketonemia traits divided into two or
three classes were studied. Linear model heritability estimates for
hyperketonemia traits were low, however, when the threshold model was used for
binary traits the estimates became slightly higher (0.07 to 0.15). Genetic
correlation between CFH and C-LA for first parity cows was high (0.97) as
expected since traits are quite similar. Moderate genetic correlations (0.47 to
0.52) were found between the endocrine fertility traits and early lactation milk
yield. Results suggest that the data on endocrine fertility traits measured by
automatic systems is a promising tool for improving fertility, specifically when
more data is available. For hyperketonemia traits, dividing values into three
classes instead of two seemed to work better. Based on the current study and
previous studies, where higher heritabilities have been found for milk BHB traits
than for clinical ketosis, milk BHB traits are a promising indicator trait for
resistance to ketosis and should be studied more. It is important that this kind
of data from automatic devices is made available to recording and breeding
organizations in the future.
PMID- 29954472
TI - Treatment of unilateral vocal fold paralysis with ansa cervicalis to recurrent
nerve anastomosis in a young adolescent: European case report.
AB - BACKGROUND: Laryngeal re-innervation in paediatric unilateral vocal fold
paralysis is a relatively new treatment option, of which there has been little
reported experience in Europe. METHODS: In this European case report of a 13-year
old boy with dysphonia secondary to left-sided unilateral vocal fold paralysis
after cardiac surgery, the patient underwent re-innervation using an ansa
cervicalis to recurrent laryngeal nerve transfer, in combination with fat
augmentation, after 12 years of nerve denervation. Perceptual analysis data, and
acoustic and laryngoscopy recordings were acquired pre-operatively, and at one
and two years post-operatively. RESULTS: The patient's perceptual voice quality
was improved. He experienced subjective improvement and is very satisfied with
the result. As expected, laryngoscopy at one and two years after surgery showed
no physiological mobility of the vocal fold concerned, but improved closure
during phonation was achieved. Electromyography showed evidence of re
innervation. CONCLUSION: Laryngeal re-innervation could be considered as a
treatment option for unilateral vocal fold paralysis in children and adolescents,
even after a long-term delay.
PMID- 29954473
TI - Incidental finding of pulmonary arterial sling during patent ductus arteriosus
surgery in a patient with Mowat-Wilson syndrome.
AB - Mowat-Wilson syndrome is a genetic condition due to a mutation in the ZEB2 gene;
it affects many systems including the cardiovascular system. The pulmonary
arterial sling originates from a failure of development of the proximal portion
of the left sixth aortic arch, resulting in an anomalous left pulmonary artery
origin from the posterior wall of the right pulmonary artery and the left
pulmonary artery crossing to the left lung between the trachea and the
oesophagus. We present a 4-month-old infant with Mowat-Wilson syndrome and left
pulmonary arterial sling, and discuss the association of these two rare
conditions. Pulmonary arterial sling is significantly more frequent in patients
with Mowat-Wilson syndrome than in the general population.
PMID- 29954475
TI - Beyond the dopamine hypothesis of schizophrenia to three neural networks of
psychosis: dopamine, serotonin, and glutamate.
AB - Psychosis is now widely hypothesized to involve neural networks beyond the
classical dopaminergic mesolimbic pathway, including serotonin and glutamate
systems as well.
PMID- 29954474
TI - Human papillomavirus prevalence and clinicopathological associations in
oropharyngeal squamous cell carcinoma in the Lebanese population.
AB - OBJECTIVES: To evaluate for the first time the prevalence of human papillomavirus
in oropharyngeal squamous cell carcinoma in a Middle-Eastern population, and to
determine associations between human papillomavirus profiles and
clinicopathological characteristics. METHODS: A retrospective chart review was
conducted of all patients treated for oropharyngeal squamous cell carcinoma at
the Hotel Dieu de France University Hospital (Beirut, Lebanon) between January
2010 and 2016. Existing formalin-fixed paraffin-embedded tumour samples were
analysed. Human papillomavirus DNA viral load and p16 expression were evaluated
using polymerase chain reaction and immunohistochemistry respectively. RESULTS:
Thirty patients (mean age of 60 years) were included. Twenty-seven per cent of
patients were p16-positive/human papillomavirus DNA positive, 53 per cent were
p16-negative/human papillomavirus DNA negative and 20 per cent were p16
positive/human papillomavirus DNA negative. Human papillomavirus 16 was the most
frequent subtype (75 per cent). Smoking and alcohol consumption were
significantly lower in the human papillomavirus positive group compared to the
human papillomavirus negative group (p = 0.049 and 0.004, respectively).
CONCLUSION: Human papillomavirus rate was lower than reported rates in Western
populations. Possible explanations include differences in social and cultural
behaviours.
PMID- 29954476
TI - Molecular Weight Determination of Aloe Polysaccharides Using Size Exclusion
Chromatography Coupled with Multi-Angle Laser Light Scattering and Refractive
Index Detectors.
AB - Background: Size exclusion chromatography (SEC)/refractive index (RI) were used
to determine molecular weight (MW) and molecular weight distributions (MWD) of
polysaccharides. In aloe product research and quality control, commercially
available pullulan and dextran are most commonly employed as calibration
standards. Significant difference in the MW and MWD were found in literature when
different methods were used. Objectives: This study was to investigate the
traditional methods and more recent technologies used to determine the MW and MWD
of Aloe vera polysaccharides. Methods: In this study, multi-angle laser light
scattering (MALS) detection was studied on three polysaccharides, 1, 2, and 3,
that were isolated and purified from A. vera leaf. The chemical structures of 1-3
were characterized as 1, 4-beta-linked glucomannans by monosaccharide composition
and glycosidic linkage analysis. Absolute MW and root-mean-square radius were
determined by MALS on the isolated aloe polysaccharides. The conditions to obtain
reliable results from MALS measurement were examined. Results: MALS analysis
demonstrates that the 1, 4-beta-linked glucomannan adopt the conformation of
random coils or hard spheres in the analytical environment of a 0.1 M NaCl
solution. Non-size exclusion effects and interactions between polysaccharide
molecules were also observed in some aloe polysaccharides in the current
analysis. The weight-average MW obtained by MALS measurement for 1, 2, and 3 are
55, 129, and 962 kDa, respectively. Comparing the results with SEC/RI calibrated
by pullulan and dextran standards, marked differences in the MWD are found. Both
overestimated the MW of 1 and 2 by factors of 4.4 and 4.2, and 2.4 and 1.6, when
using dextran and pullulan calibration, respectively. Using pullulan calibration
underestimated the MW of 3 by a factor of 3.1, but a similar result was obtained
from dextran calibration compared to MALS measurement. The two isolated aloe
polysaccharides were employed to be broad calibration standards or to be combined
with narrow polydispersity pullulan calibration standards. Several aloe samples
were tested using the different calibration curves, and the determined MWs were
compared with the results obtained by MALS measurement. Conclusions: The results
clearly indicated that until true polysaccharide standards become available MW
and MWD's will be simply relative to the standards employed and the technologies
used.
PMID- 29954477
TI - Efficacy of recombinant human C1 esterase inhibitor across anatomic locations in
acute hereditary angioedema attacks.
AB - BACKGROUND: Hereditary angioedema (HAE) may occur at or spread to multiple
anatomic locations during an acute attack. Recombinant human C1 esterase
inhibitor (rhC1-INH) is approved for treating acute HAE attacks. OBJECTIVE: To
examine the time to the beginning of symptom relief with rhC1-INH by attack
location. METHODS: Data for patients >=12 years of age with an acute HAE attack
who received rhC1-INH 50 IU/kg or placebo were pooled from two double-blind
clinical trials with open-label extensions. The time to the beginning of symptom
relief was defined as the first time point that the visual analog scale severity
score at an attack location decreased by >=20 mm versus baseline, with
persistence. Data were reported as median time values (95% confidence interval
[CI]). RESULTS: For abdominal attacks, the median time to the beginning of
symptom relief was 60.0 minutes (95% CI, 47.0-62.0 minutes; n = 194 attacks) with
rhC1-INH versus 240.0 minutes (95% CI, 45.0-720.0 minutes; n = 15 attacks) with
placebo. The median time to the beginning of symptom relief for peripheral
attacks was 105.0 minutes (95% CI, 90.0-120.0 minutes; n = 169 attacks) with rhC1
INH versus 303.0 minutes (95% CI, 180.0-720.0 minutes; n = 17 attacks) with
placebo. For oro-facial-pharyngeal-laryngeal attacks or urogenital attacks, the
median time to the beginning of symptom relief with rhC1-INH was 64.5 minutes
(95% CI, 60.0-120.0 minutes; n = 36 attacks) and 119.0 minutes (95% CI, 40.0
270.0 minutes; n = 13 attacks), respectively, versus 306.0 minutes (95% CI, 30.0
495.0 minutes; n = 6 attacks) and 320.0 minutes (n = 1 attack) with placebo.
CONCLUSION: In shortening the median time to the beginning of symptom relief of
acute HAE attacks, rhC1-INH 50 IU/kg was efficacious, regardless of attack
location.
PMID- 29954478
TI - Chemical Investigation of Major Constituents in Aloe vera Leaves and Several
Commercial Aloe Juice Powders.
AB - Background: There are a substantial number of papers in the scientific literature
reporting on the chemical composition of the Aloe vera plant. None of these
investigations are truly comprehensive nor address the differences in composition
that occur through processing variations in fresh leaves and commercially
available product forms. Objectives: This work was to analytically examine a
range of these forms and compile the findings. Methods: Fresh A. vera leaves and
a number of commercial aloe juice powders were investigated for their major
chemical constituents. Samples included fresh leaves from China and Mexico, plus
commercial powders from different manufacturers made from different plant parts
and/or manufacturing processes. The test results include moisture, ash, fiber,
protein, lipids, minerals, organic acids, free sugars, and polysaccharides. The
analytical methods employed comprise inductively coupled plasma-optical emission
spectroscopy for minerals, high-performance anion-exchange chromatography
equipped with pulsed amperometric detection for free sugars, HPLC for organic
acids, and size exclusion chromatography (SEC)-multi-angle laser light scattering
(MALS)-differential refractive index (dRI) for polysaccharide analyses. The
absolute MW and MW distribution were determined using MALS measurement. Results:
The major constituents of A. vera fresh leaf are fibers, proteins, organic acids,
minerals, monosaccharides, and polysaccharides, which accounted for 85-95% of the
total composition determined. In the commercial powdered aloe juice samples, four
major components-organic acids, minerals, monosaccharides, and polysaccharides
accounted for 78-84% of the total composition. Apart from the four major
components, products manufactured by ethanol precipitation contained high amounts
of fiber and protein, while the free sugars were removed. In ethanol-precipitated
products, the polysaccharide MW was less affected by manufacturing conditions and
the concentration of aloe polysaccharides was higher than in products made in the
nonethanol manufacturing processes. The overall chemical profiles were found to
be consistent, except for the MW and content of polysaccharides in the commercial
aloe samples analyzed, which were largely dependent on the types of manufacturing
processes employed. Conclusions: This present study provides a comprehensive
investigation of the major chemical composition of A. vera leaf and commercially
derived products. The use of the SEC combined with MALS and differential RI
detectors has proved to be an improved tool for the accurate determination of
polysaccharide MW and contents of the various commercially available A. vera
products in this study.
PMID- 29954479
TI - Ultra-High-Performance Liquid Chromatography-Isotope Dilution Tandem Mass
Spectrometry for the Determination of Phthalate Secondary Metabolites in Human
Serum Based on Solid-Phase Extraction.
AB - >Background: A multitude of biomonitoring analytical methods are applied in
urinary detection, but few are applicable to phthalate metabolites in human
serum, and those that are invariably involve complex operation. Objective: To
develop a novel method for the determination of phthalate monoesters in human
serum using solid-phase extraction (SPE) and ultra-HPLC (UHPLC)-tandem mass
spectrometry for multiple human serum sample determination. Method: Analytes in
serum samples were extracted and purified with a novel SPE cartridge named Prime
HLB and then directly injected and analyzed without eluent redissolution. After
sample extraction and cleanup, 11 phthalate monoesters were separated on a C18
chromatographic column in UHPLC. Among them, mono-isobutyl phthalate and mono-n
butyl phthalate, a pair of isomers, were successfully separated. Results: Lower
LODs of the 11 monoesters in 0.5 mL human serum were in the range of 0.03-3
ng/mL, and lower LOQs accordingly ranged from 0.1 to 10.0 ng/mL. Recoveries from
spiked bovine serum samples were in the range of 95.3-109.9%, and RSDs were 8.0
12.0%. Intra- and inter-day recoveries were in the range of 94.1-115.7%, with
RSDs <13.7%. Conclusions: The proposed method has been proved to be rapid,
simple, accurate, and sensitive, so that it may potentially be used for high
throughput biological monitoring with high efficiency and precision. Highlights:
Sample pretreatment does not require eluent drying and redissolution. Mass losses
of analytes are avoided. Operational procedures are easy and rapid. The method
has proved applicable for 11 phthalate metabolites in multiple human serum sample
determinations.
PMID- 29954480
TI - Detection of 20 Phthalate Esters in Different Kinds of Food Packaging Materials
by GC-MS/MS with Five Internal Standards.
AB - >Background: Phthalate esters (PAEs) are a group of chemical compounds widely
used as plasticizers to increase the flexibility of plastics that are used in the
manufacturing of kitchen utensils and food containers. Objective: In this study,
a simple, rapid, and sensitive method for the determination of 20 PAEs in
different kinds of food packaging materials has been developed. Methods: Samples
injected with five internal standards were extracted with acetonitrile saturated
with n-hexane and then detected by GC-MS/MS without a purification step. Results:
The standard calibration curves were linear for all analytes over the
concentration range of 5-500 MUg/L, and the correlation coefficients ranged from
0.9913 to 0.9999. The LODs and LOQs were in the ranges of 1.7-62.5 and 5.5-208.3
MUg/kg, respectively. The accuracy of this method was evaluated by measuring the
recovery from spiked samples. The recoveries of all 20 phthalates from samples
spiked at three different concentrations were measured, and the recovery was in
the range of 82.1-110.8% and the relative standard deviation range of recovery
result (n = 6) was 0.3-9.7%. Conclusions: The method presented here is simple,
rapid, and sensitive and can be applied to large-scale detection of PAEs in
plastic materials. Highlights: Instead of only one solvent, acetonitrile
saturated with n-hexane was used as the extraction solvent. Samples were
pretreated without a purification step. Five internal standards were used for
quantitative determination.
PMID- 29954481
TI - Simultaneous Extraction and Determination of Preservatives and Antioxidants in
Juice Samples by an Optimized Microextraction Method Using Central Composite
Design and Validated with Accuracy Profile.
AB - >Background: Food additives are widely used in industries. Overall, these
additives have a beneficial role, but if their concentration exceeds certain
limits, they may have an adverse effect on human health. Objective: This study
outlines the determination of benzoic acid (BA), sorbic acid (SA), butylated
hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) in juices using
dispersive liquid-liquid microextraction and HPLC-diode-array detection. Methods:
Different parameters that significantly affect the extraction efficiency were
optimized. The disperser and extraction solvents were acetone and chloroform,
respectively. The other parameters were selected and optimized using two-level
(2k) factorial and central composite designs, respectively. A full method
validation using an accuracy profile for the total measurement error was carried
out. Results: The optimized conditions were 625 MUL acetone, 350 MUL chloroform,
0.85 g NaCl, and pH 2. The validated method demonstrated good linearity with R2
>= 0.99 and good precision with the RSD of repeatability and intermediate
precision at 1.97-10.7% and 2.31-11.9%, respectively. The relative recoveries
were 96.2-105.4%, and the LODs were around 0.03 MUg/mL for all compounds. The
analysis of 41 samples revealed that BA and SA were quantified in 25 and 20
samples, respectively. BHA and BHT were not detected. Conclusions: The proposed
methodology is an appropriate tool to determine important food additives in
juices to ensure their compliance with the food additives legislation.
Highlights: The work has demonstrated that the method can be successfully used in
the simultaneous determination of four food additives in fruit juices.
PMID- 29954482
TI - Formation and Characterization of Protein Corona Around Nanoparticles: A Review.
AB - Recent years have witnessed unprecedented increase in the use of nanoparticles in
various sectors viz. electronics, catalysis, agriculture, textile, cosmetics, bio
medicine, packaging, house-holds and food-associated consumer products. This has
led to the inevitable release of nanoparticles into the environment, which can
have negative impact on living beings. Humans can also be exposed to these
nanoparticles either intentionally or accidently. Nanoparticles can enter in the
human body through food chain, inhalation, open wounds, drugs and intravenous
injections etc. In majority of these cases, the nanoparticles may pass through
the various cell layers, cell sap and finally enter into the blood. Upon
interaction with biological fluid, nanoparticles come in close proximity
particularly to the proteins present in the fluid. The assembly of proteins
surrounding the nanoparticle's surface is called as protein corona and their
complex is known as protein-nanoparticle complex. Formation of protein corona is
a vibrant and driving process, which plays a pivotal role in the functioning of
nanoparticles in biological systems. Moreover, due to interaction of proteins
with nanoparticles, conformational changes may occur in the native structure of
protein, which may lead to change in the functioning of proteins towards its
cellular interaction. The present review provides in-depth knowledge about the
formation of protein corona around nanoparticles and the factors regulating this
process. Further, it discusses various techniques that can be used for the
protein corona analysis and obtaining information about molecular consequences
upon nanoparticle's exposure. Finally, the functional aspects of protein
nanoparticle complex have been discussed in detail. In-depth understanding of
protein-nanoparticles complex can be instrumental to generate well-suited
nanoparticles with desired surface characteristics in the way to biological
application.
PMID- 29954483
TI - Colloidal Nanoparticles for Signal Enhancement in Optical Diagnostic Assays.
AB - The use of nanotechnologies for the development of highly sensitive and
affordable diagnostic assays has significantly improved the ability to detect and
characterize multiple types of biomarkers. Semiconductor and metal nanoparticles
with unique optical properties have been successfully integrated within biomarker
detection schemes for the generation and enhancement of optical signals in label
based and label-free assays. Highly sensitive label-based diagnostics has been
realized particularly via using quantum dots (QDs) as labeling probes. Similarly,
many label-free techniques that are emerging as potential complements to label
based approaches benefit from signal enhancement strategies using e.g., metal
nanoparticles. This review presents a concise overview of recent advances in
diagnostic assays that utilize nanoparticles for the generation and enhancement
of optical signals in fluorescence- and surface plasmon resonance-based
techniques. Advanced diagnostic assays that utilize nanoparticles provide major
improvements in detection sensitivity, which can potentially meet the challenging
requirements of clinical diagnostics.
PMID- 29954484
TI - Nanostructured Metal Tellurides and Their Heterostructures for Thermoelectric
Applications-A Review.
AB - Telluride's and Selenides were assessed whether it is appropriate for
thermoelectric effects. Previous researches showed that researchers strived to
progress the performance of telluride based materials in creating structures
where the entire dimensions are reduced, such as nanowires or thin films. Seebeck
and Peltier coefficient was developed by means of Telluride thermoelectric
devices. Epitaxial growth methods such as molecular beam epitaxy and metal
organic chemical vapor deposition are some of the frequent methods of acquiring
telluride thin films. Thermoelectric nano thin films and nanostructured materials
should have the properties of insulation so that it can be used as energy storage
devices and thermo electric generators. Conduction of electricity is usually
convoyed by reversible and irreversible effects, such as electrical resistance
and thermal conduction which is used to, Peltier refrigerators, generating
electricity, renewable energies and its applications. Telluride films can be used
in thermoelectric applications; these thermoelectric materials are mainly rare
metals such as (Bi), (Te), (Pb) and (Sb). Thermal conductivity, figure of merit
is advantageous factor of these energy storage devices. Thermoelectric cooler,
thermoelectric generators are the powerful sources which can be eligible due to
the use of telluride thin films. The thermal conductivity performance, figure of
merit and Seebeck and Peltier coefficients of diverse materials were conferred.
PMID- 29954486
TI - Mimicking of a Transient Protein Binding in Mammalian Cells Using a
Functionalized Magnetic Nanoparticle.
AB - Identification of binding proteins is essential for uncovering biological
mechanisms of functional small molecules and proteins, but if the binding is
transient it may be quite difficult to find the binding proteins using cell
extracts that is commonly used for target identification methods. Usually sticky
proteins bind to bait molecule first as long as cell extracts are used. In such
cases, it would be very difficult to find transient binding proteins. The best
way to circumvent the non-specific bindings might be putting bait molecules into
living cells and collects the baits after a certain period of incubation time. In
here, we evaluated a new target identification method in living cells with
magnetic nanoparticles. For the proof-of-concept, we reproduced a transient
interaction between peroxisomal proteins and Pex5p, the peroxisome guiding
protein. To that end, carboxyl group-functionalized magnetic nanoparticles were
labeled with peroxisomal targeting signal 1 (PTS1) peptide to mimic peroxisomal
proteins. The PTS1-labeled magnetic nanoparticles translocated into peroxisomes
in the mammalian cells, during which they transiently interacted with Pex5p.
These results were confirmed using a fluorescence microscope and "in cell pull
down" experiments. Conclusively, the transient interaction between peroxisomal
proteins and Pex5p in cells was reproduced with the PTS1-labeled magnetic
nanoparticles in living cells by showing its sequential translocation into
peroxisomes and transient interaction with Pex5p in parallel. This result
indicates that a magnetic nanoparticle can be a useful tool for analyzing dynamic
change of interacting proteins to a functional molecule in living cells depending
on circumstances the cells encounter.
PMID- 29954485
TI - Photo-Induced Heating in Plasmonic Nanoparticles Trapped in Thermo-Sensitive
Liquid Crystals.
AB - Thermo-sensitive liquid crystals may result, for some aspects, good host
materials for plasmonic nanoparticles. In particular they are suitable to study
and measure the temperature variations produced by photo-induced plasmonic joule
effect in the metallic nanoparticles. Combining the properties of liquid crystals
and metallic nanoparticles, allows to measure temperature variations in different
ways by exploiting the optical properties of thermotropic liquid crystals: In a
first attempt, by combining nematic liquid crystals and spherical metallic
nanoparticles, we have predicted and measured temperature changes, under a
suitable (resonant) optical illumination, by measuring the photo-thermal induced
birefringence variation. In a different experiment, we have combined cholesteric
liquid crystals and gold nanorods: Light-induced variations of structural
colorations exhibited by cholesteric liquid crystals has been used as a new
methodology to measure nanoscale heat variation with a very high sensitivity
(0.03 K).
PMID- 29954487
TI - Image of the Micro-Computed Tomography and Atomic-Force Microscopy of Bone in
Osteoporosis Animal Model.
AB - Osteoporosis, a major public health problem, is characterised by a reduction in
and deterioration of bone tissue microarchitecture, with a consequent increase in
bone frailty and susceptibility to fractures. We performed ex vivo micro-computed
tomography (micro-CT) and atomic-force microscopy (AFM) between normal and
surgically ovariectomized animals (OVX). The tibial architecture was investigated
using maximum intensity projection images. Micro-CT analysis of the tibia
metaphysis was used to calculate the trabecular spacing (Tb.Sp). Following OVX
surgery, the rats exhibited increased Tb.Sp. Between the bundles, there are holes
in the fabric with a diameter in the range of 3 to 5 MUm in normal tibia. The
diameter of hole in the osteoporosis tibia is the range of 5 to 10 MUm, and its
area increased than normal tibia. AFM can be used for the inspection of bone
surfaces and offers the possibility of quantification of local geometries, such
as pit size, collagen fibril diameters, or collagen ultrastructure. Our results
suggest that AFM will surely become one of the most important tools in the realm
of medical research for imaging such as bone and tissues.
PMID- 29954488
TI - Glutaryl Polyamidoamine Dendrimer for Overcoming Cisplatin-Resistance of Breast
Cancer Cells.
AB - OBJECTIVE: Cisplatin has limited clinical applications due to drug resistance.
PAMAM dendrimer was chosen as a vehicle to counteract cisplatin-resistance and
its mechanism was assessed. METHODS: Generation 5 Polyamidoamine dendrimer (G5)
was modified by glutaric anhydride (GA) and then conjugated with cisplatin. The
cisplatin release of G5-GA-cisplatin was evaluated at pH 5.5 and pH 7.4. The
cytotoxicity of G5-GA-cisplatin and free cisplatin was compared in cisplatin
resistant breast cancer cell line MCF-7R. The intracellular platinum content of
MCF-7R was determined using ICP-MS. The expression of Ctr1 and ATP7B of MCF-7R
cells was also evaluated. RESULTS: An average of 75 amino groups present in the
G5 PAMAM surface were converted into glutaric acid (G5-GA75) and platinum loading
was 350+/-21 MUg per 1 mg of G5-GA75. G5-Ac75-cisplatin complex exhibited
controlled release of cisplatin at different pH over a period of 96 h. After 96 h
incubation with G5-Ac75-cisplatin, cell viability was 27.47+/-2.53%, 12.18+/
0.65% and 11.62+/-0.84% using platinum concentration of 1 MUg/ml, 3 MUg/ml and 5
MUg/ml, respectively. Meanwhile, 46.33+/-5.06% cells survived even in the high
platinum concentration of 5 MUg/ml after 96 h incubation with free cisplatin. G5
GA75 led to 3-6 times higher cisplatin accumulation than free cisplatin in MCF-7R
cells, because MCF-7R cells exhibited lower Ctr1 expression and higher ATP7B
expression than MCF-7 cells. CONCLUSION: The G5-GA75-cisplatin complex displayed
greater anticancer activity than free cisplatin in the cisplatin-resistant breast
cancer cell line MCF-7R. The low levels of Ctr1 and high levels of ATP7B in MCF
7R caused G5-GA75 to allow the accumulation of cisplatin, which in turn increased
the cytotoxicity. Results indicated that glutaryl G5 PAMAM may be a potential
carrier for cisplatin targeting in breast cancer.
PMID- 29954489
TI - SWNHs (Single-Wall Carbon Nanohorns) Supervises Endoplasmic Reticulum (ER) Stress
in Hepatocellular Carcinoma.
AB - SWNHs can act as a good biocompatible nanomaterials and show potential
application in the field of drug carriers or therapy to influence biological
function on cell. HCC (Hepatocellular carcinoma) is a most common type of
malignant neoplasms in the digestive system. SWNHs have been reported to be able
to induce HepG2 cell apoptosis. In the study, we implant HepG2 cell into nude
mice and observe the effect of SWNHs on these tumor model mice. And then 38
apoptosis proteins were determined using Human Apoptosis Antibody Array kit. The
proteins related to ER stress were examined through immunohistochemical staining
and western blotting assay. Our results indicated that SWNHs did not influence on
tumor in model mice. There were no significant difference expression of the 38
apoptosis proteins in xenograft between the treatment group and control. However,
the proteins related to ER stress were increased. In summary, we identified that
SWNHs was as a stimulator of ER stress to influence the biological function of
hepatoma cells, and may be used as a potential anti-cancer agent in HCC.
PMID- 29954490
TI - BNNT/Fe3O4 System as an Efficient Tool for Magnetohyperthermia Therapy.
AB - Nanostructured materials have been widely studied aiming to biomedical
applications, primarily for the purpose of carrying drugs or molecules of
interest in a selected tissue or organ. In this context, boron nitride nanotubes
(BNNTs), when functionalized with specific moieties, could be useful as
nanovectors for delivery of proteins, drugs, and also RNAi molecules, due to
their capacity to be uptaked by cells. The introduction of magnetic nanoparticles
allows the use of such system as a hyperthermia agent. Thus, once it has been
targeted to tumor areas, it could kill cancer cells by magnetohyperthermia
therapy. In order to study this effect, magnetite nanoparticles were incorporated
into hydroxilated BNNT. The system was characterized by transmission electron
microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD)
and vibrating sample magnetometry (VSM). The results obtained show that magnetite
nanoparticles are linked to the nanotubes. Magnetic measurements show that
coercivity and magnetization were not disturbed after incorporation to the BNNT.
Based on this, a new methodology for in vitro magnetohyperthermia experiments was
developed, aiming to treat each cell group individually preserving its sterility.
The biological assays of the system demonstrate its good cell viability and the
great potential of this nanomaterial as a magnetohyperthermia agent for cancer
treatment.
PMID- 29954491
TI - Neuroregenerative Effects of Electromagnetic Field and Magnetic Nanoparticles on
Spinal Cord Injury in Rats.
AB - The present study aimed to evaluate the effect of iron oxide nanoparticles
(IONPs) along with electromagnetic fields (MF) exposure on spontaneous and
induced axonal sprouting after spinal cord injury (SCI). Adult male Wistar rats
were subjected to spinal cord transection at the T13 segment. The IONP (25
MUg/mL) embedded in 3% agarose gel was implanted at the injury site and
subsequently exposed to MF (50 Hz, 17.96 MUT, 2 hours/day for 5 weeks).
Histological analysis of spinal cord tissue showed a significant increase in the
expression of the growth-associated protein GAP-43 and it was found to be co
localized with neuronal nuclei marker and neurofilaments. The results show
sprouting from mature neurons and axons, significantly less demyelination and
more myelinated fibers were evident at the lesion site. However, no motor or
somatosensory evoked potential response was observed, suggesting lack of long
distance functional connectivity. These findings highlight the therapeutic
potential of IONPs along with MF exposure in promoting neuroregeneration after
SCI.
PMID- 29954492
TI - Cytotoxicity of Graphene Oxide (GO) and Graphene Oxide Conjugated Losartan
Potassium (GO-LP) on Neuroblastoma (NB41A3) Cells.
AB - Despite several advancements in the biomedical sciences, an efficient cancer
therapy still remains a challenge. Nanomedicines have shown potential to overcome
certain roadblocks faced in the existing treatment modalities. Losartan potassium
(LP) which is a known vasodilator also exhibits anti fibrolytic and anti
metastatic properties altogether. Further, also being a potential angiotensin II
type 1 receptor antagonist, it has been well explored for down regulating
tumourogenic biomarkers like VEGF-A (Vascular endothelial growth factor A) and
suppression of neovascularization, making it a suitable drug to target for cancer
treatment. Besides this, it too reflected the stimulation of pro apoptotic
signaling pathways. But due to its lower bioavailability and extensive hepatic
metabolism its therapeutic index reduces down. Thus, the present study is focused
on designing a nano-delivery system using graphene oxide (GO) as a nano-vehicle
and conjugated the LP with it. Then, the successful synthesis of GO and GO-LP
nano conjugates were characterized by high-resolution transmission electron
microscopy, X-ray diffraction, FTIR and UV visible spectroscopy, confirming the
formation of nanosheets. The qualitative morphological evaluation of NB41A3
neuroblastoma cell line treated with bare GO, LP and GO-LP using microscopy and
DAPI staining revealed the inhibitory action of GO-LP nano conjugate on cell
proliferation. Additionally, the cytotoxicity was also estimated using MTT (3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), Nitric oxide (NO)
and Lactate dehydrogenase (LDH) assays. The results show that GO-LP significantly
suppresses the cell viability in comparison to control and bare GO suggesting
that the designed system may express its potential to be used with existing chemo
drugs for the treatment of neural cancers.
PMID- 29954493
TI - Rapid Identification of Mixed Enteropathogenic Bacteria by Means of Au
Nanoparticles@Bacteria Using Portable Raman Spectrometer.
AB - Rapid detection of food-borne pathogens is the most critical and urgent issue
among all the current food safety problems. As enhanced substrate, nanoparticles
are widely used in surface enhanced Raman scattering (SERS) because of unique
optical and physicochemical properties. In this study, Au nanoparticles with
monodisperse and good reproducibility were synthesized by using sodium citrate
reduction method. Applying Au nanoparticles sol as enhanced substrate, a portable
Raman spectrometer had been applied for rapid detection of single and mixture
pathogenic bacterial contamination by SERS. The results indicated that
Escherichia coli, Salmonella typhimirium, Shigella flexner and Staphylococcus
aureus showed specific Raman phenotypes at 600~1700 cm-1. Generally, different
bacteria could be easily and instantly recognized by its Raman phenotypes. The PC
LDA classification model was set up by combined bacterial Raman phenotypes with
the multivariate statistical analysis. With the short-time inoculation, four
enteropathogenic bacteria could be rapidly, precisely, sensitively and
specifically identified. Furthermore, the model also had a good ability to
predict the mixed contamination. This research provides the possibility of rapid
detection in the food and biomedical fields.
PMID- 29954494
TI - Investigation of Functional Graphene/Cypermethrin Pesticide Molecules by Using
Density Functional Theory Calculation.
AB - Graphene has received tremendous interest owing to its excellence excellent in
electrical conductivity and very high specific surface area. In this work,
density functional theory (DFT) is used in order to investigate optical and
electrical properties of functionalized graphene which interacted with
cypermethrin pesticide molecules. The structures of graphene and pesticide were
designed and optimized with M06-2x/6-31G(d,p) method of calculation. Graphene was
functionalized by carboxyl, amine and hydroxyl groups to investigate the
cypermethrin molecules. The binding energy, band spectra, optical properties and
electron distribution of complexes were analyzed. The results reveal that the
functionalized graphene with hydroxyl group can highly improve the interaction
between graphene and cypermethrin with the lowest binding energy.
PMID- 29954495
TI - Enhanced Internalization of Indian Ayurvedic Swarna Bhasma (Gold Nanopowder) for
Effective Interaction with Human Cells.
AB - In the ancient traditional Indian Ayurvedic system of natural healing, gold
nanoparticles (Swarna Bhasma, gold ash) have been used for its therapeutic
benefits as far back as 2500 B.C. Ayurvedic medicinal preparations are complex
mixtures that include many plant-derived products and metals. Bhasmas date as far
back as the 8th century and are made by samskaras (processings), such as shodhana
(purification and potentiation), jarana (roasting), and marana (incineration,
trituration) in the presence of plant products, including juices and concoctions.
Previous studies characterized the physical properties of gold ash, and the
mechanisms of its entry into human cells, but only preliminary data exist on its
toxicity. Before using nanoparticles for therapeutic application, it is extremely
important to study their toxicity and cellular internalization. In the present
study, various imaging techniques were used to investigate Swarna Bhasma's (gold
nanopowder) toxicity in both cancerous and noncancerous cells (HeLa and HFF-1)
and to characterize its spectral properties. The results showed that gold ash
particles had no impact on the cellular viability of both HeLa and HFF-1 cells,
even at high concentrations or long incubation times. Moreover, it was found that
the internalization level of Swarna Bhasma to cells may be improved by mechanical
breaking of the large aggregates into smaller agglomerates. Hyperspectral images
revealed that after breaking, the small agglomerates have different spectral
properties in cells, compared to the original aggregates, suggesting that size of
particles is instrumental for the subcellular interaction with human cells.
PMID- 29954496
TI - Calcium Phosphate Silicate and Calcium Silicate Cements Suppressing Osteoclasts
Activity Through Cytokine Regulation.
AB - Calcium phosphate silicate bone cement (CPSC) can stimulate osteoblast
proliferation and promote osteogenesis, but how CPSC supress osteoclast activity
through cytokine regulation is not clear. In the current study, we synthesized
CPSC by incorporating monocalcium phosphate (MCP) into calcium silicate cement
(CSC), and analyzed the effects of CSC and CPSC on osteoclast survival with MTT.
And we found that both CSC and CPSC medium could decrease osteoclast cell
viability, and flow cytometry further revealed that CSC and CPSC could inhibit
osteoclast activity. To elucidate the underlying mechanism, related gene and
protein level of cytokines that related to osteoclast activity were evaluted. The
results demonstrated that osteoclast activity was inhibited in cells treated with
cement. The effects were associated with a number of cytokines stimulated by
cement. In conclusion, both CSC and CPSC seem to be good substitutes of bone
replacement by inhibiting osteoclast activity; the exact mechanism of how they
promote bone growth, however, needs further investigations.
PMID- 29954497
TI - Wear Mechanism of Artificial Joint Failure Using Wear Debris Analysis.
AB - Aseptic loosening is one of the main failure modes in artificial joints.
Significant information about the aseptic loosening is carried by the wear debris
of the joints. In this paper, the wear debris acquired from the ultrahigh
molecular weight polyethylene (UHMWPE) artificial joints is prepared and a
systematic research is carried out to investigate the wear mechanism of aseptic
loosening using the wear debris analysis. The hip joint simulator was used to
conduct the wear tests of the CoCrMo-UHMWPE artificial joint friction pairs. The
scanning electron microscope (SEM) was employed to analyze the wear debris
profiles. The analysis results demonstrated that the UHMWPE joints mainly
produced the roundness, tuberous, lacerated, sheet, pole-liked and strip wear
debris, and the wear mechanism of the joint aseptic loosening had a close
relationship with the morphology of the debris types. The adhesive wear, fatigue
wear and laceration under alternating stress were the main causes of the joint
failure. Based on the wear debris analysis results, a new diagnosis method using
the radar map fractal representation was proposed to diagnose the failure of the
artificial joints.
PMID- 29954498
TI - Improving the Stability of UV-Cured Materials by the Radical Scavenger Loaded
into Halloysite Nanotubes.
AB - We prepared a new size-stable UV-cured material by loading a radical scavenger, 4
methoxyphenol (MEHQ), into halloysite nanotubes (HNTs) to improve the size
stability of UV-cured products. Loading the MEHQ into halloysite nanotubes was
intended to protect the curing reaction from the typical inhibitive influence of
a radical scavenger. After the curing process, heating treatment was performed on
the cured products to accelerate the release of MEHQ from the halloysite lumen.
The Brunauer-Emmett-Teller tests and transmission electron micrographs showed
that MEHQ was successfully loaded into the halloysite lumen. The
photopolymerization kinetic curves of composites revealed that adding the MEHQ
loaded halloysite nanotubes (HNTs-M) into UV-cured materials enabled faster
photopolymerization rate than adding a simple mixture of HNTs and MEHQ. With MEHQ
loaded in HNTs, the inhibition influence of MEHQ could be reduced. The results of
the size-stability test showed that composites with HNTs-M underwent lower
deformation during daily use than neat cured materials. In particular, the volume
shrinkage of the composites with 8 wt% HNTs-M in daily use was decreased by
51.3%. The results of the release experiment showed that the release rate of MEHQ
could be increased through heating treatment. This method may be used to improve
the size-stability of UV-curable materials in the future.
PMID- 29954499
TI - Fabrication and Characterization of Ti and TiO2 Nanoparticles by Pulsed Wire
Evaporation and Transmission Electron Microscopy.
AB - Ti and TiO2 nano-sized particles were fabricated by pulsed wire evaporation (PWE)
and characterized. The differences in the size and shape distribution according
to the charging voltage, V0 (2.8 to 6.5 kV), were investigated. From the high
resolution transmission electron microscopy (TEM) images, a new phase of face
centered cubic Ti nanoparticles was observed. Electron-energy loss spectroscopy
coupled with high-resolution TEM revealed three phases in TiO2 nanoparticles:
anatase, rutile, and brookite. PWE methods and these observations highlight the
potential of developing novel nanoparticles with unprecedented structures and/or
properties.
PMID- 29954500
TI - Composites of Sulfur-Titania Nanotubes Prepared by a Facile Solution Infiltration
Route as Cathode Material in Lithium-Sulfur Battery.
AB - Achieving high energy density has been the focus of research in rechargeable
batteries. Lithiumsulfur system is attractive due to its high theoretical energy
density (2500 Wh kg-1). The major problem in Li-S system is associated with the
dissolution of lithium polysulfides formed at the cathode during discharge.
Shuttling of polysulfides between the cathode and anode during cycling reduces
the efficiency of cycling. In the present study, TiO2 nanotubes are prepared from
nanoparticles by hydrothermal route. Titania-sulfur composite has been prepared
by infiltrating sulfur solution into the TiO2 nanotubes and studied as a cathode
material in a non-aqueous electrolyte. Cycling behavior of Li-S cells fabricated
using pristine sulfur and TiO2 nanoparticle-sulfur composite is also studied for
comparison. Cells with TiO2 nanotubes exhibit better discharge capacity and
coulombic efficiency than the cells with TiO2 nanoparticles and pristine sulfur.
PMID- 29954501
TI - Fluorescent Sensing Assay for Trinitrotoluene Using Fluorescein Isothiocyanate
Conjugated Mesoporous MCM-41 Particles.
AB - In the present study, Trinitrotoluene (TNT) has been detected by the formation of
Meisenheimer complex using Fluorescein isothiocyanate (FITC) dye loaded
Mesoporous silica particles (MCM-41). FITC dye loaded mesoporous silica particles
(MCM-41/FITC) have been synthesized using (3-Aminopropyl)trimethoxysilane, APTMS
(lambdaex = 490 nm and lambdaem = 512 nm). TNT forms Meisenheimer complex with
the amine group of APTMS present on MCM-41 particles. The loading of FITC in the
pores of MCM-41 particles has been confirmed by different advanced
characterization techniques. The average diameter of mesoporous MCM-41 particles
was found about 130 nm. Pore volume is observed to decrease from 1.06 cm3/g to
0.49 cm3/g after FITC loading. The selective detection of TNT up to 0.1 ppb level
makes MCM-41/FITC particles a potential sensing material for TNT detection.
PMID- 29954502
TI - Morphology Control and Growth Mechanism Study of Quantum-Sized ZnS Nanocrystals
from Single-Source Precursors.
AB - The growing demand of metal sulfides using in various applications has in turn
greatly stimulated basic research to develop novel nanomaterials with controlled
size, shape, phase and desired properties. Specifically, ultrathin ZnS nanowires
with diameter of less than 2 nm have attracted significant interest because of
their considerable promise in sensors, phosphor host materials, photodetectors,
and other devices. A novel method for the synthesis of controlled morphology,
phase and size of ZnS nanocrystals has been developed. Especially, ultrathin ZnS
nanowires with 1.5 nm in diameter were synthesized from single-source precursor
zinc dicarbazoledithiocarbamate using oleylamine as capping ligand and solvent.
Strong quantum confinement effects related to the unique nature of these
ultrathin ZnS nanowires were observed. More importantly, we have presented the
evidence for the assembly of ultra-small ZnS nanoparticles in 1-D polymer-like
structures achieved by oriented attachment mechanism for synthesis of ultrathin
ZnS nanowires.
PMID- 29954503
TI - Magnetic NiFe2O4/Exfoliated Graphite as an Efficient Sorbent for Oils and Organic
Pollutants.
AB - This study aimed to fabricate, characterize and investigate the applicability of
nickel ferrite (NiFe2O4 decorated exfoliated graphite for adsorptive removal of
oils and organic compounds. The exfoliated graphite/NiFe2O4 was synthesized via a
simple two-step process: (i) exfoliation of the lowcost natural graphite flakes
using H2O2 as oxidizing agent and H2SO4 as intercalating agent, (ii) decoration
of magnetic NiFe2O4 using the acid citric-based sol-gel process. The synthesized
exfoliated graphite/NiFe2O4 hybrid was then applied for the sorption of diesel
oil, vegetable oil, gasoline, petroleum ether and tetrahydrofuran. Moreover, the
recyclability of the used materials was investigated using either chemical or
physical extraction method. Properties of the exfoliated graphite/NiFe2O4 hybrid
were analysed using relevant techniques such as Scanning Electron Microscopy
(SEM), Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), and
Vibrating Sample Magnetometry (VSM) and N2 adsorption/desorption measurement.
PMID- 29954504
TI - Core-Shell Fe@SiO2 Nanoparticles Synthesized via Modified Stober Method for High
Activity in Cr(VI) Reduction.
AB - In this paper, Fe@SiO2 nanoparticles (alpha-Fe nanoparticles coated with SiO2
shell) were synthesized at room temperature using the modified Stober method
combined with potassium borohydride (KBH4) reduction process. The present study
depicts the facile synthesis of Fe@SiO2 without the presence of surfactants and
stabilizers. In this experiment, KBH4 acted both as a reducing agent for iron
salt and a catalyst for hydrolysis and polycondensation of
tetraethylorthosilicate (TEOS). The Fe@SiO2 nanoparticles were characterized
using X-ray diffraction method, specific surface area (BET) technique,
transmission electron microscope (TEM), and vibrating sample magnetometer (VSM).
The optimal mass ratio of Fe in the form of anhydrous ferric chloride (FeCl3) and
SiO2) in the form of TEOS was 4:1. alpha-Fe-Fe nanoparticles (size of about 45
nm) were coated with approximately 10 nm thick SiO2 shells. Moreover, Fe/SiO2
(Fe0 nanoparticles supported by silica nanoparticles) was synthesized to compare
the results. Due to the silica shells, Fe cores cannot be oxidized when dipped in
the concentrated sulfuric acid, and hence, the removal of Cr(VI) was not weakened
in the acidic environment.
PMID- 29954505
TI - Negative-Capacitance Fin Field-Effect Transistor Beyond the 7-nm Node.
AB - In this paper, we investigate the negative-capacitance fin field-effect (NC
FinFET) and extend the design beyond the 7-nm technology node. A 7-nm-node NC
FinFET is presented using the Landau-Khalatnikov equation and the physical
equations of a 3D technology computer-aided design simulation. We propose a new
NC-FinFET with double ferroelectric hafnium zircon dioxide layers. This device
exhibits noticeable voltage gains in the sub-threshold region, can decrease
subthreshold swing (SS) effectively, has a wide-ranged uniform SS lower than 60
mV/dec, and can downscale the threshold voltage without increasing the off
current. The static noise margin of the static random access memory using the new
NC-FinFET is simulated and shows good performance with improved SS and threshold
voltage.
PMID- 29954506
TI - Superhydrophobic and Ultraviolet-Blocking Cotton Fabrics Based on TiO2/SiO2
Composite Nanoparticles.
AB - Superhydrophobic and ultraviolet (UV)-blocking cotton fabrics were prepared by
the incorporation of TiO2/SiO2 composite nanoparticles followed by
hydrophobization with hexadecyltrimethoxysilane (HDTMS). The TiO2/SiO2 composite
nanoparticles were synthesized via sol-gel reaction with tetraethyl orthosilicate
(TEOS) as the precursor in the presence of TiO2. As for the resulting products,
characterization by Fourier-transform infrared spectrometry (FTIR), X-ray
diffractometer (XRD) and scanning electron microscope (SEM) were performed
respectively. The hydrophobicity measurement and ultraviolet-blocking property
measurement showed that the obtained cotton fabric had a water contact angle of
159.3 degrees , a water shedding angle of 8 degrees and a large ultraviolet
protection factor (UPF = 115.42) with UVA transmittance of 3.35%. The
introduction of TiO2/SiO2 composite nanostructures onto fibers made the textiles
rougher, which were highly beneficial to the formation of superhydrophobic
surfaces. The high UV absorbance property of TiO2 imparted excellent UV-shielding
property to the treated textiles, and effective blocking of the photoactivity of
TiO2 by SiO2 resulted in the UV-durability of the superhydrophobicity on the
textiles.
PMID- 29954507
TI - Quantum Transition Properties of Quasi Two Dimensional and Electron-Phonon
Interacting System in ZnO and CdS.
AB - We investigated theoretically the quantum optical transition properties of quasi
2-Dimensional Landau splitting system, in ZnO and CdS. We apply the Quantum
Transport theory (QTR) to the system in the confinement of electrons by square
well confinement potential. We use the projected Liouville equation method with
Equilibrium Average Projection Scheme (EAPS). In order to analyze the quantum
transition, we compare the temperature and the magnetic field dependencies of the
QTLW and the QTLS on two transition processes, namely, the phonon emission
transition process and the phonon absorption transition process.
PMID- 29954508
TI - Autogenous Shrinkage Property of High-Performance Multi-Walled Cement-Based
Carbon Nanotubes Composites.
AB - High-performance cement-based materials have been widely used and are sensitized
to early cracks because of high autogenous shrinkage stress. In this study, the
uniformly dispersed MWCNTs were added into high-performance cement-based
materials. The autogenous shrinkage of high-performance cement-based composites
with different contents of MWCNTs was also investigated at the water to cement
ratio of 0.35, 0.30 and 0.25. It was proved that moderate incorporation of MWCNTs
decreased the autogenous shrinkage of cement-based composites. With addition of
0.05 wt.% MWCNTs, the value of autogenous shrinkage was minimal after treatment
for 7 days at the water to cement ratio of 0.35, with depressed percentage of
autogenous shrinkage even reaching 46.74%. The value of autogenous shrinkage
increased significantly decreased water to cement ratio, at the same addition of
MWCNTs. The mechanism for autogenous shrinkage was also explored according to
hydration property, porosity and microstructure of cement-based materials.
PMID- 29954509
TI - An Amperometric Sensor for Thiocholine Based on Cluster-Assembled Zirconia
Modified Electrodes.
AB - Here we report on the fabrication and characterization of cluster-assembled
nanostructured zirconia electrodes for the electrochemical detection of
enzymatically produced thiocholine. Zirconia nanostructures are produced by
Supersonic Cluster Beam Deposition on thin gold films. This technique enables
nanoscale control of the deposited film surface morphology, providing high active
surface area for electrochemical detection of the analyte, along with high double
layer capacitance and suitable charge transfer resistance of the system. The
electrochemical behavior of the electrodes has been characterized in the presence
of the Potassium ferricyanide/Potassium ferrocyanide redox couple and the system
performance showed to be enhanced starting from a thickness of the deposited
layer of 60 nm. The electrochemical response for the oxidation of an enzymatic
product was assessed by means of cyclic voltammetry, electrochemical impedance
spectroscopy and chronoamperometry. The nanostructured zirconia film yields a
good electrochemical detection of thiocholine. The limit of detection for
thiocholine under working potential of 0.810-0.820 V versus reference was found
to be comprised between 0.25 MUM and 1.3 MUM. Nanostructured electrodes,
combining gold and zirconia nanoparticles can be implemented as functional
transducers in biosensing devices, for example based on Acetylcholinesterase for
electrochemical detection of polluting agents.
PMID- 29954510
TI - CdS/ZnS Heterostructured Porous Composite with Enhanced Visible Light
Photocatalysis.
AB - Fabrication of semiconductor composites consisting of multicomponent or
multiphase heterojunctions is a very effective strategy to design highly active
photocatalyst systems. Here we present a facile design to fabricate novel CdS/ZnS
heterostructured porous sheet-like nanocomposite based on a cation-exchanged
hydrothermal procedure. Micro-structural analyses reveal that the product is a
kind of heterostructured composite with porous structure and high crystallinity.
The composite nanosheets exhibited enhanced visible-light photoactivity compared
with pure ZnS or CdS. Among them, sample of Cd0.45Zn0.55S gave the highest
degradation rate of about 99% under visible-light irradiation within 60 min when
10 mg of the sample was added into 50 mL of methyl orange in aqueous solution (10
mg/L). The enhanced photocatalytic activity was presumed to result from the
direct photoinduced interfacial charge transfer (IFCT) from the valence band (VB)
of ZnS to CdS.
PMID- 29954511
TI - Thermoluminescence from Cu Doped Lithium Tetraborate Irradiated with X-ray and
gamma Using 137Cs Radioactive Source.
AB - Lithium tetraborate (Li2B4O7) pellets prepared by using water/solution assisted
method were synthesized and characterized. Copper was used as doping material in
order to enhance the Li2B4O7 thermoluminescent properties. For synthesis heating
temperature parameters were defined at 750 degrees C for 2 hr, followed by 150
degrees C for another 2 hr. The materials were produced at five different Cu
concentrations: 0.02, 0.04, 0.06, 0.08, and 0.1 wt%. The luminescent and
morphological characterizations were performed by X-ray diffraction (XRD),
Scanning electron microscope (SEM), Photoluminescence (PL), and Ultraviolet
visible spectroscopy (UV-Vis). XRD and SEM analysis of intrinsic and doped
materials confirmed the obtained Li2B4O7 structure and show its morphology. XRD
patterns of the Li2B4O7 matched a tetragonal crystal structure. Crystals of
Li2B4O7 of an average size of 50 nm were obtained. The presence of the copper
dopant was confirmed in crystals of Li2B4O7:Cu by SEM-EDS (energy dispersive
spectroscopy X-ray). The emission spectrum of Cu doped Li2B4O7 showed a prominent
peak at 367 nm, while the main UV-Vis absorption was observed from 240 nm to 300
nm due to Cu+ ion 3d10 -> 3d9 4s transitions. The thermoluminescent (TL) response
was studied for both gamma radiation and X-ray. A 661.7 keV gamma radiation using
a 137Cs source at doses of 50, 100, 200, 300, 400 and 500 mGy was applied to
Li2B4O7:Cu (0.1 wt%) pellets. An X-ray source was used at doses of 600, 800 and
1000 mGy to irradiate pellets of Li2B4O7:Cu (0.02, 0.04, 0.06, 0.08 and 0.1 wt%).
A linear TL response was observed for both X-ray and gamma radiation. The kinetic
parameters were calculated using the peak shape method for the Li2B4O7:Cu (0.1
wt%).
PMID- 29954512
TI - One-Step Hydrothermal Synthesis of a New Nanostructure Ti07Ir03O2 for Enhanced
Electrical Conductivity: The Effect of pH on the Formation of Nanostructure.
AB - Non-carbon materials are considered as the promising candidates for carbon-based
catalyst support to increase the durability of proton exchange membrane fuel
cells (PEMFCs). Due to the high stability and good electrical conductivity of
TiO2, M-doped TiO2 (M is transition metals: Mo, Ru, V, W) is an emerging
candidate for Pt nanoparticles support on the cathode side of PEMFCs. In this
research, the synthesis mechanism of Ti0.7Ir0.3O2 nanostructure by the one-step
hydrothermal method at low temperature was studied. We found that by only
controlling the pH of the precursor solution, Ti0.7Ir0.3O2 can be synthesized
with different morphology and phase selection without any formation of mixed
oxides. In particular, Ti0.7Ir0.3O2 nanostructure synthesized at pH = 0 exhibited
concomitant anatase, brookite, and rutile phases. The spherical particles of
diameter 20-40 nm, cubic particles of 30-50 nm in side-length and rod-like
particles with 70 nm in length and 20 nm in diameter represented the anatase,
brookite, and rutile phases respectively. At a pH value of 1 or 2, the majority
of spherical nanoparticles were homogeneous at 15-20 nm in diameter. It was
observed that the electronic conductivity of novel Ti0.7Ir0.3O2 nanostructure was
significantly higher than that of the undoped TiO2. Thus the promising properties
of this new nanostructure open a new path to the much-needed fuel cell
applications.
PMID- 29954513
TI - Nanostructured Ti07Mo03O2 as Efficient Non-Carbon Support for PtRu Catalysts in
Direct Methanol Fuel Cells.
AB - This study was focused on a new strategy by investigating whether the novel
Ti0.7Mo0.3O2 material can be used as a conductive support for PtRu to prevent
carbon corrosion and improve catalyst activity as the novel Ti0.7Mo0.3O2 support
has some functional advantages. The 30 wt% PtRu/Ti0.7Mo0.3O2 catalyst showed the
highest current density at the complete potential, which is approximately 12-fold
and 1.4-fold higher than that of the commercial 20 wt% Pt/C (E-TEK) and 30 wt%
PtRu/C (JM) catalysts, respectively, at 0.6 V (NHE) toward the methanol oxidation
(MOR). Our data suggest that this enhancement is a result of the electronic Pt
structure change upon its synergistic interaction with Ti0.7Mo0.3O2 support and
the improved mass transport kinetics of PtRu/Ti0.7Mo0.3O2 compared to the carbon
support (Pt or PtRu). The PtRu/Ti0.7Mo0.3O2 catalyst exhibited a much higher
stability than carbon-supported catalysts because of the strong metal/support
interactions between the Pt particles and Ti0.7Mo0.3O2, the inherent structural
and chemical stability, and the corrosion resistance of the Ti0.7Mo0.3O2 in
acidic and oxidative environments.
PMID- 29954514
TI - Synthesis of Magnetic CoFe2O4 Nanoparticles and Their Efficient Degradation of
Diclofenac by Activating Persulfate via Formation of Sulfate Radicals.
AB - In this study, magnetic CoFe2O4 nanoparticles were synthesized by hydrothermal
method by using ferric nitrate and cobalt nitrate as raw materials. Subsequently,
physicochemical properties of the resulting CoFe2O4 nanoparticles were
systematically studied by scanning electron microscope, X-ray diffraction, N2
adsorption/desorption, Fourier transformation infrared spectroscopy and Vibration
sample magnetometer measurement. Results indicated that CoFe2O4 nanoparticles
with cubic spinel structure possessed an average diameter of 6.9 nm, specific
surface area of 103.48 m2 . g-1, saturation magnetization of 54.65 A . m2(emu . g
1) and coercivity of 1.76*104 A . m-1. Furthermore, scavenging experiments
revealed that sulfate radicals (.SO-4) was the main active species derived from
persulfates, in which 72.3% of diclofenac could be degraded within 30 min
treatment. This study provides a promising strategy to synthesize versatile
catalyst which would be potentially applied in pharmaceutical wastewater
purification.
PMID- 29954515
TI - In-Situ Template Formation Strategy for the Preparation of Nitrogen Doped Carbon
Nanocage with Graphitic Shell as Electrode Material for Supercapacitor.
AB - Nitrogen doped carbon nanocage with graphitic shell (NGCS) was fabricated through
in-situ solid reaction between calcium acetate and dicyandiamide in an inert
atmosphere followed by acid etching. The role played by the calcium acetate
(Ca(Ac)2) and dicyandiamide (DCD) during the synthesis process is one-stone-two
birds. Calcium acetate plays multiple functions: template agent, graphitization
catalyst, and carbon source. Dicyandiamide can be considered as the nitrogen
sources and the chemical reaction agent that can be reacted with calcium acetate
to form it into CaCN2. The NGCS obtained at 800 degrees C has a specific surface
area of 420 m2/g and nitrogen content of 8.87 at%. The excellent electrochemical
performance can be attributed to the combination effects of porous structure,
nitrogen doping and graphitized nanocage shell of NGCS electrode. The hollow
structure serves as the reservoir for fast electrolyte ion supplement. Nitrogen
groups not only improve the wettability of interfaces between carbon surface and
electrolyte, but also generate extra pseudocapacitance through redox reaction.
The graphitic carbon nanocage shell can enhance the conductivity and facilitates
the fast charge transfer. At a current density of 0.5 A/g, the specific
capacitance of the NGCS-800 electrode is 215 F/g. Furthermore, the NGCS-800
electrode exhibits excellent rate capability (80% capacitance retention at 10
A/g) and outstanding cycling stability (96.89% capacitance retention after 5000
cycles). These intriguing results demonstrate that nitrogen doped carbon with
graphitic shell will be highly promising as electrode materials for
supercapacitors and other energy storage and conversation applications.
PMID- 29954516
TI - Role of Particle-Particle Interaction Towards Effective Interpretation of Z
Average and Particle Size Distributions from Dynamic Light Scattering (DLS)
Analysis.
AB - Despite the widespread utilization of Dynamic Light Scattering (DLS) as an
analytical tool for particle sizing, one of the critical questions raised among
the users is on how to do proper analysis and interpretation of the data
obtained. In view of this, the present work was done to reveal the role of
particle-particle interaction towards the interpretation of Z-average and the
three types of particle size distributions (intensity-weighted, volume-weighted,
and number-weighted) obtained from DLS analysis. Experimental results showed that
Z-average for the weakly-interacting (highly stable) SiO2 particles obtained from
DLS was almost identical to that gained from TEM analysis. Meanwhile, for the
strongly-interacting (non-stable, aggregating) bare Fe3O4 particles, the Z
average obtained from DLS was ~10 times larger than TEM result. In term of
particle size distributions, it was found that all the three types of size
distributions were closely collapsed into a single bell curve for the unimodal
and monodisperse SiO2 particles; while for bare Fe3O4 particles which had been
aggregated into polydisperse structures, the three size distributions exhibited
large variation from each other. This observation implies that choosing the right
size distribution become challenging in the latter case. Additionally, it was
found that the Z-average of bare Fe3O4 particles varied significantly with the
particle concentration used for DLS measurement. Concerning with particle
aggregation kinetic, results from three independent case studies showed that the
intensity-weighted distribution provides more logical and consistent right
shifting as compared to both volume-weighted and number-weighted distributions.
PMID- 29954517
TI - Electrospinning Preparation of La-Doped SnO2 Hollow Nanofibers: An Improvement of
Their Gas Sensing Properties.
AB - SnO2 hollow nanofibers with different amount of La-doped were prepared by
electrostatic spinning method. Their composition, morphology and structure were
characterized by XRD, SEM, BET and XPS respectively and their gas sensing
properties were also investigated. The results showed that the hollow nanofibers
with the molar ratio of tin to La of 7% had the best sensitivity to ammonia of
500 ppm at the temperature of 300 degrees C, and the sensitivity value reached
480, which was 10 times that of pure SnO2. And its response time was also
significantly shortened.
PMID- 29954518
TI - High Efficiency CeO2/CNTs Modified Pt/CNTs Catalysts for Electrochemical
Oxidation of Methanol.
AB - The composite catalysts of CeO2/multi-walled carbon nanotubes (CNTs)-Pt/CNTs were
prepared. Morphologies of the resulting catalysts were characterized by
transmission electron microscopy (TEM) and X-ray diffraction (XRD) techniques.
The results indicated that most of particles have a narrow particle size
distribution, and the size distribution followed the Gaussian distribution. The
electro-catalytic activity of the CeO2 or CeO2/CNTs modified Pt/CNTs catalysts
towards the methanol oxidation reaction was examined by using the cyclic
voltammetry (CV) experiments in H2SO4 containing methanol electrolyte. It is
found that both catalysts of CeO2-Pt/CNTs and CeO2/CNTs-Pt/CNTs exhibited
significantly improved electrochemically active surface area (EAS) and high
catalytic activity toward methanol electro-oxidation, as compared with Pt/CNTs.
Furthermore, the corresponding CO-stripping test showed that the onset potential
and peak maxima in ceria incorporated platinum catalyst were shifted to lower
potentials compared to that of the ceria free platinum system. The effects of the
loading of CeO2 on CNTs on the electrocatalytic activity of the composite
catalysts for methanol oxidation were investigated. We found that the optimal
value of ceria loading on CNTs occurred at 40%.
PMID- 29954519
TI - Study on the Wettability of Ophthalmic Hydrogel Lens Containing Graphene Oxide
Nanoparticles with Wettability Measurement Method.
AB - For manufacturing ophthalmic lens, HEMA, PVP, Bis-GMA, GO nanoparticles and EGDMA
(ethyleneglycol dimethacrylate) were copolymerized in the presence of AIBN as an
initiator. After polymerization, the physical properties such as water content,
refractive index, contact angle of produced hydrogel lenses were measured. As a
result, when GO nanoparticles were added to the Ref. and Ref.-B samples, the
wettability increased due to the hydrogen bonding between the GO and the water
molecules, which were distributed on the surface. In the case of Ref.-P
containing PVP, the probability of hydrogen bonding with the water molecules on
the surface was lowered as hydrogen bonding was induced by the nitrogen of PVP
and the carboxyl group of the GO nanoparticles; thus, the wettability somewhat
decreased. Therefore, GO, which has excellent abrasion resistance, is considered
useful as a material for ophthalmic lenses with excellent wettability and
strength when added to the general hydrogel lens materials other than hydrophilic
materials like PVP.
PMID- 29954520
TI - Synthesis and Light Emitting Properties of Dithieno[3,2-b:2',3'-d]Thiophene (DTT)
Containing Conjugated Polymers for Electroluminescene Devices and Polymer Solar
Cells.
AB - Dithieno[3,2-b:2',3'-d]thiophene (DTT) has emerged as an important building block
in the synthesis of a wide variety of optoelectronic materials. Two new DTT
containing conjugated polymers, poly(dithieno[3,2-b:2',3'-d]thiophenevinylene-alt
9,9-diethylhexyl-2,7-fluorenediyl vinylene) (FLU-DTT) and poly(dithieno[3,2
b:2',3'-d]thiophenevinylene-alt-2-methoxy-5-(2-ethylhexyloxy)-p
phenylenevinylene) (MEH-DTT), were designed and synthesized. The
photoluminescence (PL) spectra of FLU-DTT and MEH-DTT in film exhibit maximum
emission peaks at 538 and 602 nm, respectively. The MEH-DTT polymer film showed
far more red-shifted maximum electroluminescene (EL) emission at 650 nm. The
photovoltaic device was also fabricated using MEH-DTT and PC71BM as active layer
and it showed power conversion efficiency (PCE) for the polymer solar cell (PSC)
as 0.59% under AM 1.5 G (100 mW/cm2) conditions.
PMID- 29954521
TI - Effect of Lanthanum Substitution on Magnetic and Structural Properties of Nickel
Ferrite.
AB - Inverse spinel ferrites have demanded substantial attention in the recent past
owing to their diverse technological deeds by conquering admirably with its
surface, finite size effects and optical properties which has its proficient
applications in photocatalytic degradation, magnetic resonance imaging and
sensors etc. The substituted La3+ ions delay the development of grain growth of
the materials in a meticulous manner compared with that of the pure Ni ferrites.
We tale development of magnetic features in La3+ substituted Ni nano-ferrites
synthesized by co-precipitation technique and then analyzed from the structural
and magnetic perspectives. A credible and thriftily doable co-precipitation
method has been the spotlight of forethought in recent decades to synthesize
these ferrite nanoparticles. Enviable inverse spinel phase has been observed, as
it is essential to modify and optimise its micro structural and magnetic
features. The phase formation and significant properties of Ni1-xLaxFe2O4
ferrites were investigated using XRD, FTIR, TEM, UV-visible, VSM and FT-Raman
techniques. The crystallite size of the as-synthesized nanoparticles were
observed after the substitution of La3+ content in the range of 8 to 15 nm. As
the dopant concentration increases the crytallite size increases and other
changes in crystallographic parameters, as well as the cation distribution also
observed. The TEM micrograph clearly reveals the cubic and the notable
polycrystalline nature. The FTIR measurements carried out in the range of 400
4000 cm-1 elucidates the occurrence of functional groups. The UV-visible spectrum
analysis reveals the optical property of as-synthesized nanoparticle and hence
their band gap was found using Kubelka-Munk plot. The magnetic parameters were
studied by vibrating sample magnetometer and the saturation magnetization of the
ferrites at the room temperature decreases with the reduction in size.
PMID- 29954522
TI - Pore Parameters-Dependent Adsorption Behavior of Volatile Organic Compounds on
Graphene-Based Material.
AB - Mesoporous graphenes (MPGs) with interpenetrating porous networks are
successfully obtained by the pyrolysis of composite gel consisting of graphite
oxide (GO) and the amphiphilic triblock copolymer (Pluronic P123) under Ar
atmosphere, wherein P123 is used as a soft-template. The as-prepared composite
gel is obtained following self-assembly and freeze-drying. The obtained MPGs have
high BET specific surface area (531-746 m2 g-1 and ink-bottle like pores with
three dimensional interconnected network. Furthermore, the specific surface area
and porous parameters such as pore volume, pore size, and pore size distribution
of MPGs can be rationally controlled by regulating the initial mass ratio of P123
to GO. With the increase of P123 ratio, the average mesopore size is decreased
from ~16.4 nm to ~9.5 nm, which is similar to the diameter size of P123 micelles.
Also, the adsorption capacities of MPG-20 for 52 indoor air standard components
(100 MUg mL-1, Supelco) are compared with two different materials, namely
commercial porous polymers (2,6-diphenyleneoxide) and reduced graphene oxide
(RGO). The result shows that MPG-20 has significantly better adsorption capacity
than RGO but also similar or slightly better than commercial porous polymer. The
mesoporous structure and surface chemistry of MPGs were the most important
factors for the enhancement of the adsorption efficiency for volatile organic
compounds.
PMID- 29954523
TI - Novel Hollow NiO@Co3O4 Nanofibers for High-Performance Supercapacitors.
AB - NiO@Co3O4 nanofibers with different mass ratio and different additives were
prepared by electrospinning process. The characterizations of the nanofibers are
investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM) and
transmission electron microscopy (TEM). Electrochemical properties are
characterized by cyclic voltammetry, galvanostatic charge/discharge measurements,
and electrochemical impedance spectroscopy. Results show that the NC-1 nanofibers
are hollow tube and comprised of many NiO and Co3O4 sheets. Furthermore, the NC-1
nanofibers have the highest specific capacitances (788 F.g-1 at the current
density of 5 mA.cm-2) and excellent cyclic performance (decreases 7% of the
initial capacitance after 1000 cycles).
PMID- 29954524
TI - Improvement of Heterojunction Nanomaterials Photoelectrochemical Properties by
Sol-Gel Synthesis and Hydrothermal Reaction.
AB - The ZnO nanorod arrays (NRs)/CuAlO2 laminar crystal thin films (LFs)/Ni
heterojunctions with delafossite structure were prepared by sol-gel synthesis for
LFs and hydrothermal for NRs. X-ray diffraction analysis demonstrates the typical
delafossite structure CuAlO2 and pure ZnO of R-3m space group. Compared with a
traditional CuAlO2/Ni laminar films (LFs) nanostructure, the photocurrent of this
heterojunction nanostructure is significantly increased. Note that a significant
blue-shift of the absorption edge and a favorable forward current to reverse
current ratio at applied voltages of -0.75 to +2 V were observed in this
heterojunction with the increase of Zn2+ ion concentration in the hydrothermal
reaction. Moreover, the photoelectrochemical characteristics recorded under AM
1.5 illumination with 100 mW/cm2 light intensity at 0 V (vs. Ag/AgCl), while the
highest photocurrent density arrive at 3.59 mA/cm2. This study demonstrates that
heterojuction nanostructure, which is easily adapted to other chemical systems,
is a promising technique for improving photoelectro-chemical properties of low
cost solar cells.
PMID- 29954525
TI - Preparation of Conductive Carbon Films from Novolac Resins by Ion Beam
Irradiation and Carbonization.
AB - In this study, thin carbon films with good electrical properties were prepared
using commercial novolac resins by ion beam irradiation and carbonization.
Novolac films were irradiated with ion beams and then carbonized under inert
atmosphere. Based on the FTIR and UV results, the novolac resins were found to be
crosslinked by ion beam irradiation without any additives. The Raman and XRD
results indicate that carbon films with pseudo-graphitic structures were formed
by carbonization of the ion beam irradiated novolac films. The sheet resistance
of the prepared carbon films decreased to 1.35 * 102 Omega/ with an increasing
fluence. The prepared carbon films showed a good electrical conductivity of ~2.34
* 102 S/cm.
PMID- 29954526
TI - Interfacial Reactions Between Graphite and Diethyl Carbonate Solutions Containing
Different Concentrations of Li.
AB - The electrochemical reactions occurring at graphite electrodes in lithium-ion
batteries using diethyl carbonate (DEC) electrolytes containing different
concentrations of LiClO4 (0.85 and 2.82 mol kg-1) were examined. The poor charge
discharge performance of the electrode in the 0.85 mol kg-1 LiClO4 in DEC was
improved considerably when employing 2.82 mol kg-1 LiClO4 in DEC as the
electrolyte. In situ electrochemical atomic force microscopy analysis revealed
that an effective film had formed on the graphite surface after the first
potential cycle when using the more concentrated solution. Charge-discharge
analysis revealed that the nature of the film was significantly different from
that formed in ethylene carbonate-based solutions.
PMID- 29954527
TI - Preparation and Characterization of Ophthalmic Polymer Containing Pyridine Group
and Platinum Nanoparticles with Initiator Behavior Using Photo and Thermal
Polymerization.
AB - To fabricate hydrophilic ophthalmic lenses, HEMA, MMA, and AA were mixed as basic
monomers, and EGDMA, a cross-linking agent, was added to make a basic
combination. To investigate optimal compatibility and conditions of photo
polymerization and thermal polymerization, hydrogel lenses were also fabricated
by using 2H2M and 2D2P as photo initiators and AIBN and AIPH as thermal
initiators. The properties of the lenses were subsequently compared. Each sample
was mixed by adding the additive, 3-hydroxypyridine, at a ratio of 1 to 10% and
stirred for about 30 minutes using a stirrer. When 3-hydroxypyridine was used as
an additive for improving functionality, the water content increased, and the
refractive index decreased. By measuring the optical properties, the UV blocking
effect was shown to have improved more 3-hydroxypyridine was added. Also, when
platinum nanoparticles were used as an additive, they were found to be uniformly
distributed on the produced lens. They did not show a great change in the water
content and refractive index of the lens.
PMID- 29954528
TI - Charge Transport Characteristics of the PEDOT:PSS Interlayer Electrode/Molecule
Physisorbed Contact in Large-Area Molecular Junctions.
AB - Here we studied the effect of electrical contact between the PEDOT:PSS conducting
polymer and the prototype benzenethiol molecules on the charge transport through
the PEDOT:PSS-electrode molecular junctions. For this study, two different
benzenethiol molecules were incorporated into the molecular junctions: 4
methylbenzenethiol (MBT) and 1,4-benzenedithiol (BDT). They have the same
backbone structure but different top end-group. By investigating the MBT and BDT
junctions with the PEDOT:PSS electrode, we demonstrated that the charge transport
characteristics were dominated by distinct electrical contact properties at the
PEDOT:PSS/molecule interface.
PMID- 29954529
TI - Interfacial Modifier Having Julolidine for the Cathode Buffer Layer in PTB
7:PC70BM Based Inverted Organic Photovoltaic Cells.
AB - The julolidine based interfacial modifier (IM-J) for cathode buffer layer
following the "donor-acceptor" design concept with julolidine substituent as an
electron donating moiety was incoporated to improve the surface properties of
ZnO. Simple treatment of metal oxide type cathode buffer materials with organic
interfacial modifier induces the enhanced photovoltaic performance and could
effectively overcome several interfacial problems in inverted organic
photovoltaic cells (I-OPVs). We studied on the coverage of IM-J on ZnO surface
with variation of solution concentrations to reduce charge recombination and
macroscopic phase separation. At the optimum condition, ZnO/IM-J (0.05 w/v%), IM
J significantly decreased the surface tension (46.1 mN/m) and improved surface
morphology (RMS roughness: 0.61 nm). As a result, compared to the unmodified ZnO
based device, the ZnO/IM-J based I-OPVs showed significantly improved power
conversion efficiency (PCE) from 7.41 to 8.07% due to the increased photocurrent
density (Jsc) and fill factor (FF). It is concluded that IM-J is one of the
promising candidates for controlling electronic property of ZnO buffer layer in
inverted organic photovoltaic cells. Also, our interfacial modified system can be
utilized in other optoelectronic devices.
PMID- 29954530
TI - Conductivity Properties of Single-Walled Carbon Nanotubes Upon the Encapsulation
of TTF and TCNQ.
AB - N-type and p-type single-walled carbon nanotubes (SWNTs) were formed via the
encapsulation of tetrathiafulvalene (TTF) and 7,7,8,8-tetracyano-p-quinodimethane
(TCNQ) inside SWNTs, respectively. Raman, near-infrared, and X-ray photoelectron
spectrometer were used to confirm the encapsulation. From measurements of the
current-voltage curves in a vacuum, it was revealed that current of TTF
encapsulated SWNTs decreased and TCNQ-encapsulated SWNTs increased comparing with
that of pristine SWNTs. This was resulted from electron-donating (TTF) and
withdrawing (TCNQ) character into SWNTs.
PMID- 29954531
TI - Blue Phosphorescent Bipyridine-Based Iridium(III) Complex for Vacuum-Deposited
Organic Light-Emitting Diodes.
AB - We have synthesized and characterized a blue phosphorescent iridium(III) complex
(dfpypy)2Ir(tftamp), which contains 2',6'-difluoro-2,3'-bipyridine (dfpypy) as
the main ligand and 4-methyl-2-(3'-trifluoromethyl-1'H-1',2',4'-triazol-5'
yl)pyridine (tftamp) as the ancillary ligand. The photophysical, electrochemical,
and electroluminescent (EL) properties of (dfpypy)2Ir(tftamp) were investigated.
Vacuum-deposited blue and white organic light-emitting diodes (OLEDs) were
fabricated using (dfpypy)2Ir(tftamp) in 1,3-bis(carbazol-9-yl)benzene (mCP) as
the emitting layer. The EL spectrum of (dfpypy)2Ir(tftamp) exhibited emission
maximum at 472 nm with a full-width at half-maximum (FWHM) of 81 nm and
Commission Internationale de L'Eclairage (CIE) coordinates of (0.17, 0.27) at 100
cd . m-2. In addition, white-light-emitting devices were fabricated, which
exhibited CIE coordinates of (0.42, 0.40) and a correlated color temperature
(CCT) of 3,237 K at 1000 cd . m-2, close to the standard warm-white light CIE
coordinates of (0.44, 0.40) and CCT of 3,000 K.
PMID- 29954532
TI - Well-Ordered Domains of 4-Fluorobenzenethiol Self-Assembled Monolayers on Au(111)
Guided by a Displacement Reaction.
AB - Displacement processes of pre-covered cyclohexanethiol (CHT) self-assembled
monolayers (SAMs) by 4-fluorobenzenethiol (4-FBT) on Au(111) were examined as a
function of displacement time by scanning tunneling microscopy (STM) and water
static contact angle (CA) measurements. STM imaging revealed that the adsorption
of 4-FBT on Au(111) in a 1 mM ethanol solution at room temperature for 24 h
generated disordered SAMs, whereas well-ordered 4-FBT SAMs with a (4?6 * ?3)R5
degrees packing structure were formed over the entire Au(111) surfaces via the
displacement of pre-covered CHT SAMs by 4-FBT molecules. The CA measurements also
showed that CA values increase with increasing displacement time, reflecting that
the displacement reaction took place and the resulting SAMs had greater
hydrophobicity compared with CHT SAMs. In this study, we found that the
displacement technique using CHT SAMs as a molecular template is very useful in
obtaining 4-FBT SAMs with a high degree of structural order and large ordered
domains.
PMID- 29954533
TI - Hydrothermal Growth and Electrochemical Performance of Carbon-Coated Porous SnO2
Nanospheres.
AB - The porous SnO2 nanospheres were fabricated by hydrothermal method and then the
carbon layer was coated as a buffer cushion through a facile hydrothermal process
in aqueous D-glucose followed by a subsequent calcination at 500 degrees C in a
nitrogen (N2) atmosphere. The materials were characterized by scanning electron
microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction
(XRD), thermogravimetric analysis and Raman spectra. Based on the experimental
results, the thickness of carbon layer could be well-controlled by hydrothermal
time and D-glucose concentration. The typical as-prepared carbon-coated porous
SnO2 nanospheres show an initial discharge capacity of 711.26 mAhg-1 and a
stabilized capacity at 414 mAhg-1 after 50 cycles. It was shown that the carbon
coated porous SnO2 nanospheres exhibited better electrochemical properties in
terms of high Columbic efficiency and rate performance, which are attributed to
the porous structure and the outer carbon layer.
PMID- 29954534
TI - Influence of Bicationic and Catanionic Surfactants Over the Morphology of
Mesoporous Nanohydroxyapatite.
AB - In the co-precipitation method, the morphology of nano Hydroxyapatite (HAp) is
usually being controlled by parameters like pH, temperature, concentration, and
the ratio of the mixed surfactants. In the present work, effective tailoring of
morphology has been done by exploiting the electrostatic interaction between
surfactants by grouping them as catanionic (Cetrimide and SDS) and bicationic
(Cetrimide and CTAB), with weight ratio of 1:1 and total concentration of 0.28
g/100 ml. The prepared samples were subjected to various characterizations like
FTIR, XRD, FESEM, HRTEM, TGA/DTA, and BET analysis. The results show that the
samples are in HAp phase, nano size and mesoporous in nature. The FESEM images
reveal the fact that the catanionic surfactant enhances the growth of particle
from sphere to hexagonal rod whereas bicationic mixture suppresses the growth and
results in a disk-like HAp. The samples were subjected to AAS test for finding
the Ca2+ ion release rate in SBF and were compared with a commercial
nanocrystalline HAp sample. The Ca2+ ion release test of the samples shows signs
of better bioactivity of disk-like HAp than that of commercial one.
PMID- 29954535
TI - Photoluminescence and Nonlinear Optical Properties of Transition Metal (Ag, Ni,
Mn) Doped ZnO Nanoparticles.
AB - ZnO nanoparticles doped with transition metal (Ag, Ni, Mn) were prepared by using
co-precipitation method. Absorption spectra showed exciton peak for ZnO
nanoparticles at 367 nm and for Ag, Ni, Mn doped ZnO nanoparticles at 328, 354 nm
and 342 nm respectively. Photoluminescence dynamics showed shallow level-trap and
deep-level emission where the intensity of deep-level trap increases with
transition metal doping due to the oxygen deficiency. Nonlinear absorption
measurements showed the two-photon absorption increasing with transition metal
following the trend Ag > Ni > Mn when excited with 532 nm, 30 ps laser pulses.
The transition metal doped and un-doped ZnO nanoparticles can be used as optical
limiters.
PMID- 29954536
TI - Synthesis of Carbon-Encapsulated Iron and Iron Nitride Nanoparticles from
Ferrocene Through Reactive Radio-Frequency Thermal Plasma.
AB - In this paper, carbon-encapsulated nanoparticles of iron and iron nitride were
synthesized using ferrocene by reactive radio-frequency thermal plasma. The
properties of the prepared nano-powders were investigated by TEM, XRD, Raman
spectroscopy and VSM. The samples obtained with zero-nitrogen plasma, contains
the carbon-encapsulated iron nanoparticles. There cores mainly composed of
ferromagnetic alpha-Fe and paramagnetic gamma-Fe, with carbon shell thicknesses
of about 5 nm. The samples synthesized by the plasma with varying nitrogen flow
rates, mainly consists of iron nitride and oxide having spherical and irregular
shape with deteriorated and disappearing carbon shell. Particle size in all
samples were 20-90 nm. Synthesized sample at zero-nitrogen condition showed a
room-temperature saturation magnetization of 19.65 emu/g, with a coercivity of
375.1 Oe. The sample prepared with optimal nitrogen flow rate had a saturation
magnetization of 35.25 emu/g at room temperature, with a coercivity and remanence
of 49.1 Oe and 0.56 emu/g, respectively.
PMID- 29954537
TI - Effect of Laser Beam Dimension on Laser-Assisted Chemical Vapor Deposition of
Silicon Nitride Thin Films.
AB - Laser assisted chemical vapor deposition based on the ultraviolet laser
illuminated in parallel to sample surface has been examined as a useful means to
deposit thin films without sample heating or damage. In this study, we
investigate the effect of enlarged laser beam towards silicon nitride film
deposition on larger sample area, relying on Argon Fluoride excimer laser beam of
193 nm wavelength to induce photolysis in SiH4/NH3 mixture. Advantages and
mechanisms of enlarged beam are presented, and further parametric trends
including the influences of reactant gas and laser parameters, and substrate
temperature are reported.
PMID- 29954538
TI - Enhancing Mechanical Properties of Flexible Graphene/ Cellulose Conductive Paper
by Chemically Modifying Cellulose Fibers.
AB - In recent years, conductive paper made of graphene and cellulose fibers has
triggered a great deal of attention due to its scalable fabrication process, low
cost, and environmentally friendliness. However, poor mechanical properties limit
its commercial applications. In this study, conductive graphene/cellulose paper
with improved elastic modulus and desirable conductivity was achieved by
chemically modifying the surface properties of natural cellulose fibers using
aqueous 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidation system. The effect
of the carboxyl content on the mechanical properties and conductivity of
graphene/cellulose paper was studied in detail. The results showed that the
carboxyl content of cellulose had a significant impact on the mechanical
properties of graphene/cellulose paper. At low carboxyl content (0.42 mmol/g),
the elastic modulus of the graphene/oxidized-cellulose conductive paper achieved
the value of 1572 MPa, which was 27.4% larger than that of cellulose/graphene
conductive paper. Meanwhile, the as-prepared paper exhibited excellent conductive
properties, and its sheet resistance was only 78.57 Omega/sq.
PMID- 29954539
TI - Research on Thermal Conductivity of Electrospun Polyacrilonitrile-Multi-Walled
Carbon Nanotubes Composite Carbon Nanofiber Papers.
AB - In recent decades, the rapid development of nanoscience and nanotechnology has
accelerated materials with high thermal conductivity, such as composite carbon
nanomaterials, since heat removal has become a crucial issue. In this work
polyacrilonitrile (PAN) incorporated with alteration of mass fraction (0.3 wt%,
0.62 wt%, 0.92 wt%, 2.74 wt%) of the multi-walled carbon nanotubes (MWCNTs) were
used to fabricate composite fibers via electrospinning. The stabilizing and
carbonization reactions of composite nanofibers are conducted in tube furnace at
280 degrees C and 1000 degrees C. The structural features of flexible composite
carbon nanofiber papers were characterized under scanning electron microscopy
(SEM), X-ray powder diffraction (XRD) and Raman spectroscopy. Special attention
of composite carbon nanofiber papers is given to cross-plane thermal conductivity
and in-plane thermal conductivity and were measured via Flash Line Analyzer. The
results proved that flexible composite carbon nanofiber papers are promising heat
sink radiator for a variety of applications including flexible optical and
electronic devices.
PMID- 29954540
TI - The Micro-Analysis Estimation of 3D FinFET ICs in High Temperature Operation.
AB - An integrated circuit failure mode in inter metal layer dielectric micro
delamination of the advanced 16 nm FinFET process in high temperature operating
test was investigated and presented by micro-analysis firstly in the paper. With
the smaller size in metal level and device level, the joule heat and temperature
effect inversion (TEI) become the significant concerned point in the new
technology node. Through high temperature operation test, it's verified in the
commercial system-on-chip product combined application processor function. With
series of experimental result and failure analysis, a high temperature caused
functional fail was demonstrated. The localized joule heat was generated from IC
operating current which induced by the voltage and temperature. High temperature
and voltage overstress induced the ICs higher joule heat generated locally which
is a new reliability concern in advanced process layout plan and the power
consideration by circuit design view. For FinFET IC's working conditions (ex:
environmental temperature) and application (ex: high processor usage or high
performance), the whole chip design should be well simulated and estimated before
entering mass production stage. The failure characteristic in this study provides
a hint to reconsider the factor of localized heating in the advanced process
system-on-chip circuit design and layout shrinkage in application.
PMID- 29954541
TI - Synthesis and Electroluminescent Properties of Quinoline-Substituted Anthracene
Derivatives for Organic Light-Emitting Diodes.
AB - In this study, two anthracene derivatives with quinoline moieties were
synthesized. To investigate their electroluminescent (EL) properties,
multilayered OLEDs with the following sequence; indiumtin-oxide (ITO)/N, N'-di(1
naphthyl)-N, N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine (NPB) (20 nm)/Blue emitting
materials (30 nm)/bathophenanthroline (Bphen) (30 nm)/lithium quinolate (Liq) (2
nm)/Al (100 nm) were fabricated using these materials as emitters. Two devices
exhibited EL in blue to sky-blue regions. Especially, a device using 2,3-diphenyl
6-(10-(naphthalen-7-yl)anthracen-9-yl)quinoline (1) as an emitting material
exhibited blue emission with a luminous efficiency, a power efficiency, an
external quantum efficiency, and Commission International de L'Eclairage (CIE)
coordinates of 1.01 cd/A, 0.43 lm/W, 0.80% at 20 mA/cm2, and (0.17, 0.22) at 6.0
V, respectively.
PMID- 29954542
TI - Electric Heating Performance of Pyrolyzed Photoresist Films Prepared by Proton
Irradiation and Pyrolysis.
AB - In this study, pyrolyzed photoresist films (PPFs) were prepared using commercial
SU8 photoresist by proton irradiation and pyrolysis. SU8 thin films were
irradiated with high-energy proton ions and then pyrolyzed in a tube furnace at
1000 degrees C under inert atmosphere. The carbonization yield of the PPFs
increased with an increasing fluence due to the formation of more crosslinked
network structures at a higher fluence. The electrical resistance decreased with
an increasing fluence due to the higher remaining thickness and carbonization
yield at a higher fluence. Therefore, the PPFs prepared at 1 * 1016 ions/cm2
showed the maximum temperature of 150 degrees C at 20 V and a high electric
power efficiency of 1.57 mW/ degrees C.
PMID- 29954543
TI - Effect of Synthesis Time and Composition on Magnetic Properties of FeCo
Nanoparticles by Polyol Method.
AB - This study investigated the effect of synthesis time and composition on magnetic
properties of FeCo nanoparticles. Fe75Co25, Fe66Co34, Fe52Co48 nanoparticles were
synthesized by the polyol method. The saturation magnetization of Fe75 Co25,
Fe66Co34, Fe52Co48 nanoparticles was 178 emu/g, 191 emu/g and 197 emu/g,
respectively. The coercivity of Fe75 Co25, Fe66Co34, Fe52Co48 was 113 Oe, 131 Oe
and 89.2 Oe respectively. The synthesis time of Fe52Co48 nanoparticles was also
varied (2 h and 3 h) to determine the optimal synthesis time. The saturation
magnetization of Fe52Co48 synthesized for 2 h, 3 h was 243 emu/g, 202 emu/g,
respectively. The coercivity of Fe52Co48 synthesized for 2 h and 3 h was 46 Oe
and 111 Oe, respectively. The highest saturation magnetization and lowest
coercivity was obtained using a synthesis time of 2 h. Based on these results, it
was confirmed that Fe52Co48 had the highest saturation magnetization and lowest
coercivity among all of the compositions tested, and optimal synthesis time was 2
h.
PMID- 29954544
TI - Detection of Actin Filament and Cofilin Interaction Change by Actin Filament
Curvature Decreasing.
AB - Actin filament senses mechanical forces and it is transduced into biochemical
signals during many cellular processes. In the disassembling process of actin
filaments, cofilin plays a central role as the actin filament depolymerization.
In this study, we evaluated a quantitative analysis of the actin filament-cofilin
interaction change dependent upon the actin filament curvature decrease using
atomic force microscopy (AFM) and a fabricated wave-like substrate. A wave-like
substrate was fabricated by a maskless photo-lithography of a spin coated film on
a glass substrate, and graphene oxide sheet was used for the decreasing of non
specific interaction between protein and the substrate. By single-molecule force
spectroscopy, we determined rupture force of actin filament-cofilin binding on
the wave-like substrate and a flat substrate. The rupture force of actin filament
cofilin binding at the curvature of -1.35 MUm-1 showed a value approximately 4
times higher than the rupture force at the curvature of -0.15 MUm-1. The present
study will provide the possibility and quantitative evidence that mechanical
stress on cytoskeletal filaments can modulate how they interact with their
binding proteins.
PMID- 29954545
TI - Impact of Plasmonic Parameters on 7-nm Patterning in Plasmonic Computational
Lithography.
AB - For the wavelength reduction to overcome the diffraction limit of the optical
lithography, the surface plasmon lithography (SPL) has lower cost and simpler
system configuration than the extreme ultraviolet (EUV) lithography. In this
paper, for the below 10-nm critical dimension (CD) as one of critical challenges
in the lithography technology, SPL based on the SP interference and metamaterial
in bowtie and hexahedron structures is proposed and demonstrated by using
computer simulations such as the rigorous coupled-wave analysis (RCWA) method and
the finite difference time domain (FDTD) method. For 193-nm wavelength, the
minimum FWHM (the full width at half maximum) of the transverse magnetic (TM)
intensity in xz plane (and yz plane) is 10-nm (and 7-nm) in a bowtie plasmonic
structure. For hexahedron structures, the minimum 30-nm FWHM of TM intensity with
193-nm wavelength is improved to the minimum 16-nm FWHM by using metamaterial and
SP interference.
PMID- 29954546
TI - Effect of Reducing Agent on Preparation and Electroactivity of MnO2/Graphene
Composite Electrode for Capacitors.
AB - Supercapacitor electrodes materials with improved electrochemical properties were
prepared by synthesizing manganese dioxide (MnO2) in an aqueous solution of
graphene having a wide specific surface area and high electrical conductivity.
MnO2/graphene composites were synthesized by reducing potassium permanganate with
three kinds of reducing agent (ethanol, ethylene glycol, DMF). TEM-image
confirmed that the MnO2/graphene composite which was reduced by ethanol had a
small average particle size. Electrochemical properties were characterized by
cyclic voltammetry (CV) and galvanostatic charge-discharge test in 1 M Na2SO4
aqueous electrolyte solution. The MnO2/graphene composite reduced by ethanol
showed higher specific capacitance than the MnO2/graphene composite reduced by
ethylene glycol or DMF. It was concluded that the manganese dioxide reduced by
ethanol having a small average particle size, resulting in a large specific
surface area and low impedance characteristics.
PMID- 29954547
TI - Importance of Effective Surface Smoothness on the Electrical Performance of
Organic Thin-Film Transistors.
AB - We presented further analysis to explain how the surface morphology influence the
mobility of the organic thin film transistors with gate insulator having large
undulated surface (GU-OTFTs) and introduced a new parameter in order to clearly
understand the relation between surface roughness and field-effect mobility. The
average of the slope between two adjacent points on the surface of a gate
insulator, or effective surface smoothness (ES), was closely investigated. A
smooth-contact-pressing (SCP) process affected the surface smoothness of the
P(VDF-TrFE) insulator with a significant change in root-mean-square roughness
(Zrms). It was found that the ES gives better explanation for the variation of
the field-effect mobility of the GU-OTFTs than the Zrms.
PMID- 29954548
TI - Effects of the Methyl Group on the Emission Efficiency of the Red Phosphorescent
Iridium(III) Complexes for OLEDs.
AB - Novel red phosphorescent iridium(III) complexes, namely (MN-Q)2Ir(tmd), (MN
MQ)2Ir(tmd), (PT-P)2Ir(tmd) and (PT-MP)2Ir(tmd) were synthesized for the red
phosphorescent organic lightemitting diodes (phOLEDs). The ligands have sites of
both the electron donor and acceptor in a molecule. The main ligands were
synthesized by the Suzuki coupling reaction, and comprised an electron donor and
an electron acceptor group. Subsequently, the iridium(III) complexes were
synthesized by the Nonoyama reaction and their photochemical luminescence
properties were investigated by ultraviolet-visible and photoluminescence
spectroscopy. The manufactured devices were characterized by current density
voltage-luminance, power efficiency, external quantum efficiency, as well as
their electroluminescence spectra. Finally, the effects of the trifluoromethyl
group on the emission efficiency of the organic light-emitting diodes were
investigated by comparing the energy levels and luminescence efficiency of the
three iridium complexes.
PMID- 29954549
TI - Colloidal Silica Templated Mesoporous Carbons from a Maltose Solution for Use in
Supercapacitor Electrodes.
AB - A series of disordered mesoporous carbons (DMC) are synthesized via the colloidal
silica template method by varying the mass ratio of silica to maltose from 0.4 to
1.4. A gradual improvement in the surface area and porosity of the DMC is
apparent with an increase in the ratio of silica to maltose. The capacitance of
the DMCs tends to increase linearly with their surface area. In particular, the
DMC synthesized at a mass ratio of 1.4 exhibits the largest surface area of 1,152
m2/g and the highest capacitance of 175.4 F/g, comparable to the capacitance of
other porous carbons with large surface areas (>2,000 m2/g). This feature may be
attributed to its unique structural properties, such as the high pore
interconnectivity allowing for easy access of the electrolyte ions. We believe
that a higher capacitive performance can be achieved through further optimization
studies (e.g., searching for better carbon precursors and adjusting the mass
ratio of silica to carbon precursor).
PMID- 29954550
TI - Effects of Silicone Oil on Electrowetting to Actuate a Digital Microfluidic Drop
on Paper.
AB - The effects of an immiscible, lubricating polydimethylsiloxane fluid, referred to
as silicone oil, on the static deformation and on the dynamic motion of a water
drop on paper induced by electrowetting were investigated. The deformation of a
drop on a hydrophobic film of amorphous fluoropolymers top-coated with less
hydrophobic silicone oil was much more predictable, reversible and reproducible
than on the uncoated surface. In the dynamic tribological experiment for a
sliding drop along an inclined surface, a significant decrease in the friction
coefficient, with an unexpected dependency of the contact area, was observed.
Based on the curve fitting analysis, the shear stress and the net friction force
were estimated quantitatively. Because of the tribological effect and the reduced
shear friction force of the oil film, the static and the dynamic electrowetting
states of the water drop were enhanced.
PMID- 29954551
TI - Preparation of Nanoporous Polymer Membranes Utilizing Water Pressure and Solvent
Mixtures.
AB - For the nanopore generation in cellulose acetate (CA), specific solvents
consisting of water and acetone was utilized with water-pressure. Co-solvent
ratio was changed w/w 8/2 to w/w 9/1 (Acetone/H2O) in 10% cellulose acetate
solution. When the water pressure was vertically applied to CA free standing film
with co-solvent, the water flux was observed, meaning the pore generation in
polymer. The water flux of these CA polymer films was investigated depending on
pressures. The polymers obtained from the 9:1 acetone/H2O mixture showed an
improved water flux at 8 bar, which was attributable to the relative decrease in
the water content with respect to acetone. The chemical and physical properties
of the membranes were studied using SEM, FT-IR, porosimetry, and TGA experiments.
PMID- 29954552
TI - Optical and Structural Characteristics of Glancing Angle Deposition Synthesized
Er2O3 Nanowires.
AB - The Er2O3 nanowires (NWs) were synthesized on Si substrate by using glancing
angle deposition technique inside E-beam evaporator. The field-emission gun
scanning electron microscopy (FEG-SEM) images showed perpendicular and highly
porous Er2O3 NWs with average diameter ~50 nm and length ~350 nm. The
crystallinity of the Er2O3 NWs improved with annealing but degraded at higher
temperature annealing at 900 degrees C. Transmission electron microscopy (TEM)
images show the unsymmetrical NW growth and grain size enhancement with
increasing annealing temperature. In addition, two-fold enhanced absorption was
observed for as deposited as compared to the annealed samples. A low intense
photoluminescence was obtained for the as deposited sample as compared to the
annealed samples due to the presence of defects and dangling bonds. The as
deposited Er2O3 NW also showed a hydrophobic surface property with a contact
angle of as high as 107.4 degrees due to the air trapped in between Er2O3 NWs
and oxygen vacancies which turned to hydrophilic surface with contact angle 27
degrees and 25 degrees when annealed at higher temperature of 750 degrees C
and 900 degrees C respectively.
PMID- 29954553
TI - Improvement of the Tribological Properties of a Lithium-Based Grease by Addition
of Graphene.
AB - Graphene with layer number less than seven, prepared by a mechanical exfoliation
method, was used as a friction-reducing additive to a lithium-based grease. The
graphene was characterized via AFM, TEM, and Raman spectroscopy. The as-prepared
graphene had few defects according to the characterization analysis and appeared
to be composed primarily of sheets averaging 1-4 atomic layers. When the graphene
was added to a lithium-based grease, the lubrication and antiwear properties of
the grease were improved, as quantified by friction coefficient and wear scar
measurements. The weld point of the lithium-based grease increased proportionally
with graphene loading. At the maximum graphene loading tested (2 wt%), the weld
point was 1.6 times that of the pure lithium-based grease. Hence the mechanical
properties of the graphene sheets played an important role in improving the
tribological properties of the grease.
PMID- 29954554
TI - Characteristics of Cu2O:Na Thin Films Prepared by DC Magnetron Sputtering Method
at Low Temperature.
AB - In this work, the success of doping Na into Cu2O thin films by reactive DC
magnetron sputtering method at low temperature is described for the first time.
The characteristics of crystal structure, morphology, optical, electrical
properties and binding of elements in Cu2O:Na thin films are carefully
investigated. The Cu2O:Na thin films have exhibited high electronic conductivity
as p-type semiconductor and absorption in visible range. The highest hole
concentration on the order of 1018 cm-3 and the lowest resistivity of 6.726 Omega
. cm according to 6.56% Na impurities in Cu2O:Na lattice are also detected. The
role of Na impurity in Cu2O structure is proposed that based on the changing of
structure and alignment of elements.
PMID- 29954555
TI - Advanced Ti0.7W0.3O2 Nanoparticles Prepared via Solvothermal Process Using
Titanium Tetrachloride and Tungsten Hexachloride as Precursors.
AB - The degradation of Pt-based catalysts is considered as the main barrier to the
commercialization of fuel cells. M-doped TiO2 (M is a transition metal) has been
investigated to improve the stability of electrocatalysts. Recently, W-doped TiO2
materials have been found as a good catalyst support for the photocatalyst
applications but their application in Proton-exchange membrane fuel cell
application has rarely been reported. In addition, the agglomeration of
nanoparticles, which are synthesized from the organic precursor, has been
reported. Here, we report Ti0.7W0.3O2 nanoparticles prepared via a one-step
solvothermal method with inorganic precursors without using surfactants or
stabilizers for restricting nanoparticle agglomeration. The properties of the
material were measured by XRD, TEM, BET, and electronic conductivity. The mean
particle size of ~5 nm, the high specific surface area of 126.471 m2/g and a
moderate electronic conductivity of 0.014 S/cm were obtained for the sample
prepared at 220 degrees C for 4 h. It was observed that using inorganic
precursors to prevent particle agglomeration is more advantageous compared to
organic precursors as mentioned in previous reports.
PMID- 29954556
TI - One-Step Electrodeposition of Nanostructured NiCoOx Films for Highly Efficient
Water Oxidation Reaction.
AB - Nanostructured nickel-cobalt binary oxides (hydroxides) with efficient water
oxidation activity are favorable for water electrolysis. Herein, we successfully
developed a simple and fast anodic electrodeposition route to fabricate amorphous
NiCoOx films on indium tin oxide (ITO) substrate. The crystalline structure,
surface morphology, and surface composition of deposited films were characterized
by X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray
photoelectron spectroscopy (XPS), respectively. The optimized NiCoOx provided a
synergistic effect for efficient water oxidation, with an overpotential of 250 mV
and a low Tafel slope of 48 mV . dec-1. The NiCoOx films also exhibited an
enhanced long-term durability.
PMID- 29954557
TI - Magnetic Nanoparticle-Based Lateral Flow Immunochromatographic Strip as a
Reporter for Rapid Detection of Melamine.
AB - Magnetite nanoparticles (MNPs) Fe3O4 and r-Fe2O3 were surface-modified with
poly(ethylene glycol) (PEG) in order to improve their specificity and
bioactivity. PEG and the anti-MEL monoclonal antibody (mAb) were successfully
immobilized on the surface of MNPs and characterized using FTIR, UV-Vis and TEM
analyses. Surface modification of MNPs-PEG-mAb conjugates of a variety of sizes
and magnetite types was employed to design and prepare labels for use in a
lateral flow immunoassay (LFIA) to test whether the size of the conjugate can
affect the performance of the assay. The results showed that the detection limit
was mainly determined by the size of the MNPs-PEG-mAb conjugate. Under optimized
conditions, a detection limit of 0.4 ppm for melamine was achieved using Fe2O3
PEG-mAb, which was almost 5-fold lower than that of the Fe3O4-PEG-mAb conjugate
(2.2 ppm).
PMID- 29954558
TI - Dichroic Behavior of Gold Nanoparticles Synthesized in Aqueous Solution with
Insufficient Reducing Agent.
AB - The spherical gold nanoparticles (AuNPs) typically are red in solution. However,
in this study, the dichroic and spherical AuNPs were synthesized using a modified
seeding growth method under reducing agent insufficiency in an aqueous solution.
This particular AuNP solution is orange in reflected light and red in transmitted
light. The reflectance curves confirm that the dichroic AuNPs are different from
the classic AuNPs. With particle assembling, the AuNP solution is fainter orange
in reflected light, but purple in transmitted light when the color of classic
spherical AuNP solution is purple in both lights. Furthermore, the aggregated
nanogold solutions were added to HAuCl4 solutions with the addition of an
insufficient amount reducing agent. The solution changed from faint orange to
bright orange in reflected light and from purple to blue in transmitted light. It
indicates that the gold assembling under a reducing agent insufficiency, not the
shape of AuNP, causes the dichroic phenomenon. To the best of our knowing, this
is the first study to report how the AuNP is synthesized, not the shape, affects
the color of the AuNP.
PMID- 29954559
TI - Functionalized Graphene for Mechanical Property Enhancement of Polymer
Composites.
AB - Because of its high strength and high toughness, graphene has been widely used in
mechanical reinforced composites. In general, the mechanical enhancement depends
mainly on the properties of graphene itself and the number of surface chemical
functional groups attached on it. In this paper, we report a method to improve
the mechanical performance of polymer by using a kind of functionalized reduced
graphene oxide (F-RGO), i.e., the F-RGO is prepared by chemical treatment, and
then the F-RGO/polyvinylidene fluoride (PVDF) composite films are obtained by
spin coating. Because the chemical treatment can increase the number of
functional groups on the surface and edge of F-RGO, these functional groups make
the F-RGO sheets strongly coupled with PVDF molecules, so as to achieve the
purpose of mechanical enhancement. The experimental results reveal that the
mechanical properties of the F-RGO/PVDF composite films are improved for 42%
times, when comparing with regular RGO/PVDF composite films.
PMID- 29954560
TI - Improvement of Liquid Crystal Alignment Using Novel Photo-Activators.
AB - Photo-activator is a kind of additive that can improve the anchoring energy by
attacking some of the bonds of polyimide (PI). Photo-activators were synthesized
from the reaction of cyclohexanone oxime with three different anhydrides,
respectively. Each activator generates different active radicals when irradiated.
These fragmented and activated radicals are responsible for the liquid crystal
(LC) alignment of PI film. The reactivity was confirmed through UV-Visible
spectroscopy. All the three photo-activators had characteristic bimodal-shaped
absorption peaks at 270~280 nm. The photofragmentation reactions were completed
within 1 min of UV irradiation, which implies that the activators are highly
reactive to UV light. The short reaction time is very useful for liquid crystal
display (LCD) factory applications. The photo-activator using crotonic anhydride
(CAP) showed the highest surface anchoring energy, of 6.92 * 10-5 J/m2, compared
to that of the other activators and that obtained by rubbing methods; (1.11 * 10
5 J/m2). This result was obtained due to resonance stabilization from the allyl
radicals of CAP. The photo-activator using acetic anhydride (AAP) reached its
maximum anchoring energy in less than 3 min of irradiation, which is the shortest
optimum irradiation time. Considering the fact that this process does not require
additional procedure and time, the photo-activators can be considered an innovate
additive.
PMID- 29954561
TI - Pyridine-, Pyrimidine-, and Triazine-Based Thermally Activated Delayed
Fluorescence Emitters.
AB - Novel thermally activated delayed fluorescence (TADF) materials with pyridine
(Pd), pyrimidine (Pm), and triazine (Trz) as electron acceptors and carbazole
(Cz) as an electron donor (TmCzPd, TmCzPm, and TmCzTrz) were designed, and the
effect of the number of nitrogen (N) atoms with acceptor units was investigated
by comparing their electronic and optical properties for blue organic light
emitting diodes (OLEDs). Using density functional theory (DFT) and time-dependent
DFT calculations, we obtained the electron distributions of the highest occupied
molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), and the
energies of the lowest singlet (S1)and lowest triplet (T1) excited states. The
calculated energy difference (DeltaEST) between the S1 and T1 states of TmCzPm
(0.200 eV) and TmCzTrz (0.186 eV) were smaller than that of TmCzPd (0.395 eV). We
show that TmCzPm would be a suitable blue OLED emitter because it has
sufficiently small DeltaEST values, which is favorable for a reverse intersystem
crossing process from the T1 to S1 states, and an emission wavelength of 473.1 nm
with sufficiently large oscillator strength for fluorescence.
PMID- 29954562
TI - The Effect of Heteroleptic Dual Acceptors on Dye-Sensitized Solar Cells.
AB - A novel carbazole-based organic dye with heteroleptic dual electron acceptors
(cyanoacrylic acid and thieno[3,4-b]pyrazine acid) on each side of a quinoxaline
was designed, and its electronic and optical properties were investigated
theoretically for dye-sensitized solar cells (DSSCs). To gain insight into the
factors responsible for photovoltaic efficiency, density functional theory (DFT)
and time-dependent density functional theory (TD-DFT) calculations of these dyes
were performed. The absorption spectrum of the dyes showed different forms
because of the different energy levels of the molecular orbital (MO) of each dye
and the intramolecular energy transfer (EnT). Considering the overall properties,
the asymmetric organic dye containing the heteroleptic dual acceptors showed a
competitive conversion efficiency, greater red-shift, broader absorption spectra,
and higher molar extinction coefficient compared to a single acceptor in the
conversion efficiency of the DSSCs. These results indicate that heteroleptic dual
acceptors produces good photovoltaic properties for DSSC.
PMID- 29954563
TI - Synthesis and Characterization of Benzodithiophene-4,8-Dione-Based Copolymers for
Polymer Solar Cells.
AB - A novel series of benzodithiophene-4,8-dione (BDD)-based copolymers,
poly[(4,4,9,9-tetrakis(4-hexylphenyl)-4,9-dihydro-s-indacenodithiophene-2,7-diyl)
alt-(1,3-bis(2-ethylhexyl)-5,7-di(thiophene2-yl)benzodithiophene-4,8-dione)] (P1)
and poly[(5,5,11,11-tetrakis(4-hexylphenyl)dithieno[2,3-d: 2',3'-d']-s
indacenodithiophene-3,9-diyl)-alt-(1,3-bis(2-ethylhexyl)-5,7-di(thiophene-2
yl)benzodithiophene-4,8-dione)] (P2), which have the same acceptor moiety but
different donor segments, have been designed and synthesized for use as donor
materials in solution-processable polymer solar cells (PSCs). The optical and
photovoltaic properties of the copolymers were investigated. The band gaps of the
copolymers were in the range 1.91-1.92 eV. Under optimized conditions, the BDD
based polymers showed power conversion efficiencies (PCEs) for the PSCs in the
range 2.52-2.92% under AM 1.5 illumination (100 mW/cm2). Among the copolymers,
P1, which contained an indacenodithiophene donor unit, showed a power conversion
efficiency of 2.92% with a short circuit current of 7.30 mA/cm2, open circuit
voltage of 0.92 V, and a fill factor of 0.43, under AM 1.5 illumination (100
mW/cm2).
PMID- 29954564
TI - Drug Release Behavior of Doxorubicin Hydrochloride-Loaded Poly(L-Lactic
Acid)/Hydroxyapatite/Gelatin by Surface Modification of Hydroxyapatite.
AB - The doxorubicin hydrochloride (DOX)-loaded poly(L-lactic
acid)/hydroxyapatite/gelatin (PLLA/a-HA/gelatin) particle was prepared by
emulsion/solvent evaporation method using CH2Cl2 as a solvent. HA nanoparticles
were prepared via a facile chemical precipitate method and HA nanoparticles were
functionalized by adding aminopropyltriethoxysilane (APTS) under microwave
radiation. The physical and chemical properties of HA and modified HA were
characterized by XRD, TEM, FT-IR, and XPS. Furthermore, the release of DOX from
PLLA/a-HA/gelatin was also estimated. Results indicated that HA was successfully
functionalized via APTS and functionalized HA has primary amino groups on its
surface which improved the surface chemical compatibility between HA and PLLA
matrix. The prepared PLLA/a-HA/gelatin was considered as a drug release carrier
to study sustained release behavior of doxorubicin hydrochloride (DOX). The
PLLA/a-HA/gelatin can effectively prolong the release time of DOX and exhibits a
stable and sustainable drug release which indicates that the PLLA/a-HA/gelatin
nanocomposite material could serve as a potential carrier for novel drug release
system.
PMID- 29954565
TI - Ammonia Borane Promoted Synthesis of Graphene Aerogels as High Efficient Dye
Adsorbent.
AB - Graphene aerogels (GA) hold great promise as a practical adsorbent to remove
contaminants from water thanks to their high specific surface area and stable
chemical properties. In this work, we demonstrated a strategy by introducing
ferrous ions-ammonia borane as a synergistic reducing agent for hydrothermal
reduction of graphene oxide to synthesize high-performance graphene aerogel
adsorbents. Reducing agent system features four aspects: (1) Ferrous ions
themselves as reducing agent, (2) Ferrous ions as catalyst for ammonia borane
decomposition to release hydrogen, (3) Released hydrogen as a secondary reducing
agent, (4) Involved hydrogen gas bubbles facilitating the formation of pores in
GA. As-synthesized GAs exhibited larger specific surface area and smaller pore
diameter than only using ferrous ions as reducing agent, which benefit a lot to
the adsorption and water cleaning. Adsorption experiments showed that as
synthesized GAs was high efficient in the adsorption of both cationic dye
(Rhodamine B) and anionic dye (Orange G) with adsorption capacity as high as
103.6 mg.g-1 and 87.4 mg .g-1, respectively, which is comparable to the most of
state-of-the-art sorbents. The adsorption rate was greatly improved. Besides, the
great adsorption performance was not limited to a certain kind of dye which is
different from that of most dye adsorbents. Furthermore, kinetic investigations
showed the adsorption followed a pseudo-second-order kinetics model, indicating a
chemical adsorption. The adsorption isothermal studies revealed that the
adsorption process was more likely took place in a monolayer manner. Thanks to
the facile synthesis and excellent adsorption performance, the as-prepared GAs
can be potentially applied to the practical water treatment.
PMID- 29954566
TI - Facile Hydrothermal Synthesis of ZnWO4 for Enhanced Photocatalytic Performance.
AB - ZnWO4 with controllable morphology was successfully synthesized via a facile
hydrothermal method. The relationships between the structure, morphology, and
catalytic activity were systemically studied by varying both the hydrothermal
time and pH value. The optimal synthesis conditions for ZnWO4 with superior
catalytic activity were a hydrothermal time of 12 h and a pH value of 10.
Impressively, the highest photocatalytic activity for the degradation of RhB was
91% for 60 min under ultraviolet light. The increased photodegradation
performance was mainly ascribed to the high crystallinity and enlarged surface
area of the optimal ZnWO4.
PMID- 29954567
TI - Synthesis and Characterization of Advanced Nanomaterials: Tin-Doped Indium Oxide
(ITO) and Platinium Deposited on Tin-Doped Indium Oxide (Pt/ITO).
AB - This article describes the synthesis and characterization of tin-doped indium
oxide (ITO) and platinum nanoparticles deposited on ITO. For different
calcination temperatures, the tin-doped indium oxide nanoparticles (ITO NPs) were
synthesized successfully by a nonaqueous sol-gel method with indium
acetylacetonate and tin bis(acetylacetonate) dichloride in oleylamine as the
precursors. The ITO sample that calcinated at 500 degrees C exhibited a
spherical morphology with a narrow range of the particle size distribution (15-20
nm). Moreover, the electrical conductivity of the sample (1.242 S/cm) was higher
than many different non-carbon supports. In addition, 20% platinum nanoparticles
(Pt NPs) were also deposited uniformly on the ITO supports via chemical reduction
process using NaBH4 as the reducing agent. The size of Pt NPs was about 5 nm and
the crystalline structure of ITO supports remained unchanged.
PMID- 29954568
TI - Co3O4 Nanosheets Anchored on SiO2 Nanospheres for Non-Enzymatic Glucose Sensor.
AB - The electrochemical sensing performance is sensitive to the surface area. To
achieve superior performance, we design and anchor Co3O4 nanosheets on the
surface of SiO2 nanospheres via a simple solvothermal method, which possess large
sensing interface and exposed catalytic sites due to the 2D structure and edge
terminated feature. Based on these combined structural advantages, the present
sample is employed as an ideal platform for non-enzymatic glucose sensing and
exhibits high sensitivity, low detection limit, and wide linear range for glucose
electrocatalytic oxidation, enabling it as a promising candidate for enzyme-free
amperometric sensor for glucose determination.
PMID- 29954569
TI - The Temperature Dependences of the Electron-Piezoelectric Potential Phonon
Interacting System of Quasi Two Dimensional System in GaN and ZnS.
AB - We investigated theoretically the temperature dependence of the quantum optical
transition of quasi 2-Dimensional Landau splitting system, in GaN and ZnS. We
apply the Quantum Transport theory (QTR) to the system in the confinement of
electrons by square well confinement potential. We use the projected Liouville
equation method with Equilibrium Average Projection Scheme (EAPS). Through the
analysis of this work, we found the increasing properties of Quantum Transition
Line Shapes (QTLSs) and the Quantum Transition Line Widths (QTLWs) of CdS and GaN
with the temperature we also found that QTLW, gamma(T) of ZnS < gamma(T) of GaN
in gamma = 394 MUm.
PMID- 29954570
TI - A Novel Emulsion-Based Replica Method for the Synthesis of Mesoporous Carbon.
AB - We present a novel approach for the synthesis of large-pore mesoporous carbon
with a highly porous structure, based on an oil/water (O/W) emulsion templating
method. For the formation of oil-in-water emulsions with nanoscale oil droplets,
polyvinylpyrrolidone was used as an emulsifier. Mesoporous carbon materials with
large mesopores were successfully synthesized via a three-step process: (1)
polymerization in the oil-in-water emulsion, (2) filtration, and (3)
carbonization. We confirmed that the pore size of the carbon can be significantly
reduced through a modified O/W emulsion method. The mesoporous carbon materials
prepared without an activation step exhibited an appreciable surface area (705
m2/g) and a noticeable capacitive performance of ~100 F/g at 2.0 A/g. We believe
that the approach presented here can be widely applied to the synthesis of
mesoporous carbon using various carbon sources, and the structural properties of
the mesoporous carbon can be improved through proper optimization.
PMID- 29954571
TI - Delignification, Carbonization Temperature and Carbonization Time Effects on the
Hydrothermal Conversion of Salacca Peel.
AB - Hydrochar from the hydrothermal treatment of biomass is considered as a potential
precursor for activated carbons (AC) which has been widely utilized not only for
adsorbents but also for energy storage application. The advantages of hydrochar
from hydrothermal treatment include its high Oxygenated Functional Group (OFG)
and high porosity. The authors have been working on the biomass conversion for
energy storage application. In our study, salacca peel was used as a biomass
source. In previous research for the preparation of AC, conventional
carbonization and activation methods were used, resulting in a high surface area
of AC. In the current research, the authors investigated the biomass conversion
in hydrothermal conditions. Water at a subcritical condition (with temperatures
of 200, 225 and 250 degrees C and at a pressure of 50 MPa) and carbonization
time of 4, 5 or 6 hours, with or without delignification, were critical in the
research to investigate the conversion of salacca peel into hydrochar. The
produced hydrochar from 225 degrees C, 5 h was chemically activated and compared
to commercially-AC. The hydrochar and AC were then used as electrodes for the
supercapacitor, and capacitance was measured by cyclic voltammetry (CV). The
results showed that the capacitance of hydrochar was higher than that of AC while
ACs from salacca peel exhibited much higher levels of capacitance compared to
commercially-AC.
PMID- 29954572
TI - Supramolecular Adducts of Anionic Porphyrins and a Biocompatible Polyamine:
Effect of Photodamage-on Human Red Blood Cells.
AB - Supramolecular adducts obtained by interaction between the anionic porphyrin meso
tetrakis(4-carboxyphenyl)porphyrin (TPPC) or its zinc(II) derivative (ZnTPPC)
with a biocompatible amino-terminated polypropylene or poly(ethylene oxide)s
(Jeffamines) has been investigated. The interaction with the polymer allows the
stabilization of the porphyrins in their monomeric form under physiological
conditions. The photodynamic properties of the supramolecular adducts were
explored by typical 1O2 indirect detection. Their photodynamic action were
evaluated in vitro using human red blood cells (HRBCs) under different
experimental conditions. The morphology of erythrocytes was investigated by
optical microscopy after incubation with porphyrin compounds and light
irradiation. The images show loss of their normal biconcave profile and an
incoming spiny configuration with blebs evident on their surfaces.
PMID- 29954573
TI - Reduction of Macro-Porous Silica by the Aluminum for Anode Material of Lithium
Ion Batteries: Effect of SiO2/Al Ratio.
AB - Macro-porous silicon, which can be used as an anode material for lithium-ion
batteries (LIBs), was synthesized by the reduction of macro-porous silica, which
had been prepared by template method, using aluminum metal fine powder as the
reducing agent. A TEOS-PMMA (tetra-ethyl-ortho-silicate, poly-methyl-meta
acrylate) mixture solution was used as a precursor to prepare the macro-porous
silica. PMMA was synthesized as spherical type nano-beads using a suspension
polymerization method. Silica gel was formulated by the hydrolysis of TEOS and
macro-sized pores were formed in the silica particles by the decomposition of
PMMA during the thermal treatment at high temperatures. The prepared macro-porous
silica was mixed with aluminum fine powder in methyl alcohol, and then treated at
high temperature under argon-gas conditions for the reduction of silica. The
silica/aluminum ratio was controlled to 0.5, 0.75, 1.0, 1.5 and 2.0, and the
reducing temperature was controlled in the range, 550-700 degrees C. The
formation of silicon was confirmed by X-ray diffraction and X-ray photoelectron
spectroscopy.
PMID- 29954574
TI - Nanoscale Removal of Picosecond Laser Ablation for Polymer.
AB - This paper analytically investigates the picosecond laser ablation of polymer.
Laser-pulsed ablation is a well-established tool for polymer. However the
ablation mechanism of laser processing for polymer has not been thoroughly
understood yet. This study utilized a thermal transport model to analyze the
relationship between the ablation rate and laser fluences. This model considered
the energy balance at the decomposition interface as the ablation mechanisms and
is applied to predict the laser-ablated depth of Acrylonitrile Butadiene
Styrene/PolyVinyl Chloride (ABS/PVC). The calculated variation of the ablation
rate with the logarithm of the laser fluence agrees with the measured data. The
effects of material properties and processing parameters on the ablation depth
per pulse are discussed for picosecond laser processing of ABS/PVC.
PMID- 29954575
TI - Water Absorption and Physicochemical Characterization of Novel Zeolite-PMAA-co
PAAm Nanocomposites.
AB - The growth in global population has caused an increase in the demand for food
production, leading to an increase in the use of agrochemicals. Their overuse
causes serious damage to the environment. In this way, nanocomposite hydrogels
are promising materials for use as carrier vehicles for the controlled release of
agrochemicals, which helps reduce the damage caused by their indiscriminate use.
In this work, a novel hydrogel nanostructure based on carboxymethylcellulose
(CMC) and zeolite with a poly(methacrylic acid)-co-polyacrylamide (PMAA-co-PAAm)
support network was synthesized. The CMC polysaccharide increased the zeolite
stability in the solution. Increasing the concentration of acrylamide (AAm)
monomer improved the mechanical stability of the nanocomposites. FTIR, XRD and TG
results confirmed the presence of zeolite in the PMAA-co-PAAm matrices. In
addition, the zeolite decreased the water absorption of the nanocomposites from
33 +/- 2 g/g to approximately 22 +/- 1 g/g, but increased the thermal stability
of the nanocomposites. However, the reduction in water absorption in saline
solutions was more significant in hydrogels without zeolite. Fertilizer
desorption studies confirmed the controlled release behavior and this trend may
be improved by zeolite structure. Thus, the presence of zeolite increased the
amount of monobasic potassium phosphate (KH2PO4) release from 250 to 275 mg of
fertilizer per gram of hydrogel. Controlling the water absorption and kinetic
properties by adjusting the nanocomposite constituents may increase the
applicability of the composites in agriculture, specifically as carrier vehicles
in the controlled release of agrochemicals.
PMID- 29954576
TI - Effects of Seeding Layer Annealing Temperature on Physical and Morphological
Structure of Ga/F Co-Doped ZnO Nanostructures.
AB - In this work, effects of annealing temperature of seeding layer on structural
properties and morphologies of Ga/F co-doped ZnO nanostructures synthesized by
hydrothermal process were investigated by varying the annealing temperature of
seed layer as 300-500 degrees C. The ZnO seeding layers were deposited onto
cleaned glass substrates by dip-coating technique using zinc acetate dehydrate
(CH3COO)2Zn.2H2O as starting coating precursor. The Ga/F co-doped ZnO
nanostructures were then grown on these seed layers by conventional hydrothermal
process using Zn(NO3)2, NH4F, GaN3O9 and hexamethyltetramine as Zn, F and Ga
sources, respectively. Effect of seed layer annealing temperature on
morphologies, structural and Photoluminescence properties was investigated by X
ray diffraction (XRD), Field emission scanning electron microscope (FE-SEM), and
Photoluminescence spectra, respectively. Variation of annealing temperature of
seed layers can significantly result to the difference in morphological,
structure and shape of the as-synthesized nanostructure products. It is found
that the increase in annealing temperature leads to alternation in their shape
from vertically-aligned nanosheets to nanorods with their average size ranging
from 50 to 200 nm. Furthermore, the luminescence could be ascribed to the
different contributions of the defect emissions, such asthe increase in the
oxygen vacancy (VO) emissionor the decrease of the Zinc vacancy (Vzn). However,
it can be speculated from the photoluminescence that the incorporated Ga and F
substitute into ZnO.
PMID- 29954577
TI - Effect of Metal (Mn, Co, Zn, Ni) Doping on Structural, Optical and Photocatalytic
Properties of TiO2 Nanoparticles Prepared by Sonochemical Method.
AB - Metal-doped TiO2 nanoparticles (Metal = Mn, Co, Zn, Ni) were synthesized by
sonochemical method accompanying post calcination process using metallic nitrates
of manganese, cobalt, zinc, nickel with various metal contents from 0-5 mol% and
titanium isopropoxide as a starting precursors. Sodium hydroxide (NaOH) base was
used as a precipitating agent. The influence of ultrasound operated at 750 W 20
kHz on the crystalline structure of metal-doped TiO2 nanoparticles has been
characterized by X-ray diffraction (XRD) while morphologies and grain size of the
nanoparticles were monitored by field emission scanning electron microscope (FE
SEM). The optical absorptivities and corresponding band gaps were evaluated by
diffuse reflectance spectroscopy (DRS). The performance of photocatalytic
activities of metal-doped TiO2 nanoparticles against aqueous organic dye
Rhodamine B (RhB) under visible light was investigated. The results reveal that
their crystallinity of synthesized metal doped TiO2 nanoparticles is in mixed
phase between anatase, rutile and brookite with calcination temperature at 500
degrees C for 3 h and their crystalline of all samples are shown. The
incorporation of metal dopant on the photocatalytic performance of TiO2 exhibits
a significant enhancement in its photocatalytic activities under visible light
due to the decrease in band gap energy of metal doped TiO2 nanoparticles.
PMID- 29954578
TI - Ta and Ru Seed Layers Effect on the Crystallinity and Wettability of Co60Fe20V20
Films.
AB - The following structures are deposited under the conditions (a) glass/Ru(X
nm)/Co60Fe20V20(5 nm) and (b) glass/Ta(Y nm)/Co60Fe20V20(5 nm) at room
temperature (RT), where X and Y is from 5 nm to 10 nm. X-ray diffraction (XRD)
patterns of glass/Ru(X nm)/Co60Fe20V20(5 nm) and glass/Ta(Y nm)/Co60Fe20V20(5 nm)
reveal a weak crystallization at peak beta-(200) as the thicknesses of Ta
increase from 8 nm to 10 nm, and the patterns indicate an amorphous state as the
thicknesses of all Ru films and Ta thicknesses increase from 5 nm to 7 nm. The
average contact angles of glass/Ru(X nm)/Co60Fe20V20(5 nm) and glass/Ta(Y
nm)/Co60Fe20V20(5 nm) are less than 90 degrees with testing liquids deionized
(DI) water and glycerol. The average contact angle of water on the surface is
nearly 90 degrees, indicating it is hydrophobic. Moreover, the maximum surface
energy of glass/Ru(9 nm)/Co60Fe20V20(5 nm) and glass/Ta(10 nm)/Co60Fe20V20(5 nm)
are 44.5 mJ/m2 and 37.4 mJ/m2, demonstrating that the high surface energy
corresponds to a strong adhesion, which can be combined with a magnetic tunneling
layer of MgO or AlOx and is compatible with other semiconductor processes in
magnetic recording media and photoelectric applications.
PMID- 29954579
TI - A 1T Dynamic Random Access Memory Cell Based on Gated Thyristor with Surrounding
Gate Structure for High Scalability (Journal of Nanoscience and Nanotechnology,
Vol. 18(9), pp. 5919-5924 (2018)).
PMID- 29954580
TI - Differential Effects of Deep Brain Stimulation of the Internal Capsule and the
Striatum on Excessive Grooming in Sapap3 Mutant Mice.
AB - BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for patients
with obsessive-compulsive disorder (OCD) that do not respond to conventional
therapies. Although the precise mechanism of action of DBS remains unknown,
modulation of activity in corticofugal fibers originating in the prefrontal
cortex is thought to underlie its beneficial effects in OCD. METHODS: To gain
more mechanistic insight into DBS in OCD, we used Sapap3 mutant mice. These mice
display excessive self-grooming and increased anxiety, both of which are
responsive to therapeutic drugs used in OCD patients. We selected two clinically
relevant DBS targets through which activity in prefronto-corticofugal fibers may
be modulated: the internal capsule (IC) and the dorsal part of the ventral
striatum (dVS). RESULTS: IC-DBS robustly decreased excessive grooming, whereas
dVS-DBS was on average less effective. Grooming was reduced rapidly after IC-DBS
onset and reinstated upon DBS offset. Only IC-DBS was associated with increased
locomotion. DBS in both targets induced c-Fos expression around the electrode tip
and in different regions of the prefrontal cortex. This prefronto-cortical
activation was more extensive after IC-DBS, but not associated with behavioral
effects. Furthermore, we found that the decline in grooming cannot be attributed
to altered locomotor activity and that anxiety, measured on the elevated plus
maze, was not affected by DBS. CONCLUSIONS: DBS in both the IC and dVS reduces
compulsive grooming in Sapap3 mutant mice. However, IC stimulation was more
effective, but also produced motor activation, even though both DBS targets
modulated activity in a similar set of prefrontal cortical fibers.
PMID- 29954581
TI - The posttraumatic activation of CD4+ T regulatory cells is modulated by TNFR2-
and TLR4-dependent pathways, but not by IL-10.
AB - : Platelets modulate the immune system following injury by interacting with CD4+
T regulatory cells (CD4+ Tregs). The underlying mechanisms remain unsolved. We
hypothesize paracrine interactions via Tumor necrosis factor-alpha (TNFalpha)-,
Toll like receptor-4 (TLR4)-, and Interleukin-10 (IL-10). In the murine burn
injury model, CD4+ Treg activation pathways were selectively addressed using
TNFR2-, TLR4- and IL-10-deficient mice. The CD4+ Treg signalling molecule PKC
theta was analyzed using phospho-flow cytometry to detect rapid cell activation.
Thromboelastometry (ROTEM(r)) was used to assess platelet activation. Injury
induced significant early activation of CD4+ Tregs, disruption of TNFR2 and TLR4
activation pathways resulted in lower activity. The disruption of IL-10 crosstalk
had no significant impact. Selective disruption of paracrine interactions is
associated with changes in posttraumatic hemostasis parameters. TNFR2- and TLR4
dependent pathways modulate the activation of CD4+ Tregs following trauma. In
contrast, we did not observe a role of IL-10 in the posttraumatic activation of
CD4+ Tregs. ONE SENTENCE SUMMARY: TLR4- and TNFR2-dependent mechanisms, but not
IL-10-dependent pathways, modulate the anti-inflammatory response of CD4+ Tregs
following trauma.
PMID- 29954582
TI - Physical injury, health, and well-being: Role of stress perception.
AB - OBJECTIVE: Physical injuries are common occurrences that can have substantial
implications for mental health and well-being. Ample studies indicated that
increased levels of perceived stress is associated with increased prevalence of
general health problems, as well as reduced health-related quality of life. Thus,
the goal of the present study was to examine the long-lasting association between
bodily injuries and general health. In addition, the role of stress perception in
moderating the association between injury and general health was assessed.
METHODS: Two-hundred and forty victims of past injury and 251 non-injured
participants completed a self-report health inventory questionnaire assessing
illness prevalence during the six-month period prior to the study. In addition,
they completed the short-form Medical Outcomes Survey (MOS SF-36) questionnaire
and the Perceived Stress Scale. RESULTS: Victims of past injuries reported higher
incidences of illness, mainly upper respiratory infections and fever, compared to
non-injured participants. In addition, injured participants reported poorer
perceived health status, including reduced general health, physical functioning,
and health beliefs. Perceived stress levels were similar in injured and non
injured participants, however, correlations between perceived stress and self
reported medical outcomes were stronger in injured participants compared to non
injured controls. CONCLUSIONS: Past physical injuries are associated with
increased incidence of general health concerns and poorer health-related well
being. Moreover, injured individuals do not report increased stress perception;
however, when stressed, injured individuals are more affected and health-related
quality of life is reduced. Promoting well-being in individuals who have suffered
a significant injury is, thus, a clinical necessity and a pressing social
priority. This study highlights the role of stress perception in the association
between physical injury and health, and may assist in providing better multi
disciplinary care for the injured.
PMID- 29954583
TI - Vitamin E supplementation in people with cystic fibrosis: A Cochrane review
summary.
PMID- 29954585
TI - Do patients with migraine experience an increased prevalence of falls and fear of
falling? A cross-sectional study.
AB - OBJECTIVE: To assess the prevalence of falls and fear of falling in patients with
migraine compared with controls. DESIGN: Cross-sectional. SETTING: Tertiary
headache clinic. PARTICIPANTS: This study consisted of 105 controls and 105
consecutive patients diagnosed with migraine with aura (MA, n=35), migraine
without aura (MO, n=35) and chronic migraine (CM, n=35). MAIN OUTCOME MEASURES:
Patients were interviewed using a questionnaire containing questions about the
history of falls and impairment in balance, and completed the International Falls
Efficacy Scale (FES-I). Groups were contrasted using Student's t-test and
analysis of variance, and prevalence ratios were estimated. RESULTS: Falls and
self-reported impairment in balance are more prevalent in patients with migraine
(54% and 69%, respectively) than in controls (2% and 2%, respectively). In
particular, patients with CM and MA reported a greater mean number of falls
during the previous year {CM 1.4 [standard deviation (SD) 2.2]; MA 2.2 (SD 2.3)}
compared with patients with MO [0.5 (SD 1.0); P <0.04] and controls [0.05 (SD
0.2); P <0.002]. The prevalence ratio of falls was greater in patients with MA
(7.2; P <0.002) and CM (4.5; P <0.002) compared with controls. Patients with
migraine experienced a high level of concern about falls during their daily
activities compared with controls (29.8 vs 20.1 points in the FES-I
questionnaire; P<0.0001). CONCLUSIONS: The balance impairment of patients with
migraine may have a functional impact. Migraine is associated with risk of
falling, and patients exhibit a higher prevalence of impairment in balance, falls
and fear of falling.
PMID- 29954587
TI - Preventing rural to urban spread of Ebola: lessons from Liberia.
PMID- 29954586
TI - Neuronal, astroglial and locomotor injuries in subchronic copper intoxicated rats
are repaired by curcumin: A possible link with Parkinson's disease.
AB - We aim herein to assess the neurotoxic effects of subchronic Cu-exposition
(0125%) for 6 weeks on dopaminergic and astroglial systems then locomotor
activity in rats as well as the probable therapeutic efficiency of curcumin-I (30
mg/kg B.W.). We found that intoxicated rats showed a significant impairment of
Tyrosine Hydroxylase (TH) within substantia nigra pars compacta (SNc), ventral
tegmental area (VTA) and the striatal outputs together with loss expression of
GFAP in these structures. This was linked with an evident decrease in locomotor
performance. Co-treatment with curcumin-I inverted these damages and exhibited a
significant neuroprotective potential, thus, both TH expression and locomotor
performance was reinstated in intoxicated rats. These results prove a profound
dopaminergic and astroglial damages following subchronic Cu exposition and new
beneficial curative potential of curcumin against subchronic Cu-induced
astroglial and dopaminergic neurotoxicity. Consequently, we suggest that Cu
neurotoxicity may be strengthened in vivo firstly by attacking and weaking the
astroglial system, and curcumin could be prized as a powerful and preventive
target for the neurodegenerative diseases related metal element, especially
Parkinson's disease.
PMID- 29954588
TI - Loop colostomies are safe in anorectal malformations.
AB - AIM OF THE STUDY: Divided colostomy (DC) has been recommended in anorectal
malformations (ARMs) with previously reported advantages of decreasing overflow
into the distal limb and urinary tract infections (UTIs). Skin bridge loop
colostomy (LC) is a technically easier alternative without an increase in these
complications. We report our institutional experience of LC in ARM. METHODS:
Retrospective study (Institution-approved Clinical Audit) reviewing the clinical
records of all patients with ARM undergoing stoma formation in a single UK
tertiary pediatric surgical center (2000-2015). Data collected included type of
ARM, associated anomalies, type and level of colostomy, time to stoma closure,
complications and UTIs. RESULTS: One hundred and eighty-two (95 female) patients
underwent colostomy formation for ARM. The vast majority (171/ 94%) underwent LC;
9 (5%) had a divided colostomy (DC) and 2 (1%) had no available data. The
spectrum of defects in girls included rectovestibular (62/65%), rectovaginal
(4/4%) and cloaca (29/31%). In boys, 71 (82%) had a fistula to the urinary tract
and 16 (18%) presented with a perineal fistula. Urological abnormalities
coexisted in 87 (47.8%) patients. Thirty five (21%) patients developed UTIs.
Among the 19 girls who developed UTI, 8 had rectovestibular fistula and 11 had
cloaca. Of the 16 boys who developed UTI, 14 had a fistula to the urinary tract
and 11 had an independent urological abnormality. The mean time from stoma
formation to stoma closure was 10 (3-52) months. Complications were reported in
22 (12%) LCs. Fifteen patients (9%) developed a stoma prolapse following LC with
10 (6%) requiring surgical revision. CONCLUSIONS: This is the largest reported
series of outcomes following LC for ARM. LC is easier to perform and to close,
requiring minimal surgical access, with comparable complications and outcomes to
those published for DC. TYPE OF STUDY: Retrospective comparative study. LEVEL OF
EVIDENCE: III.
PMID- 29954589
TI - Endopyelotomy versus redo pyeoloplasty for management of failed pyeloplasty in
children: A single center experience.
AB - PURPOSE: We compared endopyelotomy to redo pyeloplasty for the treatment of
failed pyeloplasty in children to identify factors that may have an impact on
outcome and favor one procedure over the other. METHODS: Of 43 patients with
recurrent UPJO, EP was performed in 27 and RP was performed in 16. Age, gender,
side, presentation of secondary UPJO, hospital stay, complications and success
rates were compared. Success was defined as radiographic relief of obstruction as
determined by ultrasound or diuretic renography at latest follow-up. RESULTS:
Mean (Range) patient age was 7.2 years (range 6 months to 17 years) in EP (group
1) while 7.4 (range 6 months to 17 years) in RP (group 2). EP technique consisted
of retrograde cold-knife in 17 patients, retrograde holmium laser in 8 and
antegrade cold-knife in 2. RP was performed in 16 patients. All the patients with
failed EP had a stricture greater than 15 mm. Mean length of the narrowed
ureteral segment was 17.8 mm in the failed EP group vs 10 mm in the successful
group (p < 0.001). Mean Hospital stay was 1 day for the EP group and 5 days for
the RP group (p < 0.001). Mean follow-up was 17 months (range 12 to 43) after EP
and 21 months (12 to 51) after RP. There was no statistical significance between
both groups regarding the postoperative degree of hydronephrosis, parenchymal
thickness, split renal functions and renal drainage. The overall success was
(86%); the success was nonsignificantly higher in RP (93.8%) vs (81.5%) in EP.
CONCLUSION: In selected children, retrograde endopyelotomy is safe and may give
comparable short-term outcomes as open redo pyeloplasty for correction of
secondary UPJO after failed pyeloplasty. Narrowed ureteral segment greater than
15 mm and preoperative grade 4 hydronephrosis were factors significantly
associated with a poor outcome after EP. A LEVEL-OF-EVIDENCE RATING FOR
CLASSIFYING STUDY QUALITY: LEVEL III Retrospective comparative study.
PMID- 29954590
TI - Prevalence of antiphospholipid antibodies in an Australian cohort of patients
with unprovoked venous thromboembolism.
PMID- 29954591
TI - Pilomatrical carcinosarcoma: report of a case with comparative genomic
hybridisation analysis.
PMID- 29954592
TI - Evolution of the modern baboon (Papio hamadryas): A reassessment of the African
Plio-Pleistocene record.
AB - Baboons (Papio hamadryas) are among the most successful extant primates, with a
minimum of six distinctive forms throughout Sub-Saharan Africa. However, their
presence in the fossil record is unclear. Three early fossil taxa are generally
recognized, all from South Africa: Papio izodi, Papio robinsoni and Papio
angusticeps. Because of their derived appearance, P. angusticeps and P. robinsoni
have sometimes been considered subspecies of P. hamadryas and have been used as
biochronological markers for the Plio-Pleistocene hominin sites where they are
found. We reexamined fossil Papio forms from across Africa with an emphasis on
their distinguishing features and distribution. We find that P. robinsoni and P.
angusticeps are distinct from each other in several cranial features, but overlap
extensively in dental size. Contrary to previous assessments, no diagnostic
cranio-mandibular material suggests these two forms co-occur, and dental
variation at each site is comparable to that within P. h. ursinus, suggesting
that only one form is present in each case. P izodi, however, may co-occur with
P. robinsoni, or another Papio form, at Sterkfontein Member 4. P izodi appears
more primitive than P. robinsoni and P. angusticeps. P. robinsoni is slightly
distinct from P. hamadryas subspecies in its combination of features while P.
angusticeps might be included within one of the modern P. hamadryas varieties
(i.e., P. h. angusticeps). No definitive Papio fossils are currently documented
in eastern Africa until the Middle Pleistocene, pointing to southern Africa as
the geographic place of origin for the genus. These results have implications for
Plio-Pleistocene biochronology and baboon evolution.
PMID- 29954594
TI - Changing patterns of patent ductus arteriosus surgical ligation in the United
States.
AB - Optimal management of patent ductus arteriosus (PDA) is unclear. One treatment,
surgical ligation, is associated with adverse outcomes. We reviewed data from the
Kids' Inpatient Database (2000-2012) to determine if PDA ligation rates: (1)
changed over time, (2) varied geographically, or (3) influenced surgical
complication rates. In 2012, 47,900 infants <1500g birth weight were born in the
United States, including 2,800 undergoing PDA ligation (5.9%). Ligation was more
likely in infants <1000g (85.9% vs. 46.2%), and associated with necrotizing
enterocolitis (59.2% vs. 37.5%), BPD (54.6% vs. 15.2%), severe intraventricular
hemorrhage (16.4% vs. 5.3%), and hospital transfer (37.6% vs. 16.4%). Ligation
rates peaked in 2006 at 87.4 per 1000 hospital births, dropping to 58.8 in 2012,
and were consistently higher in Western states. Infants undergoing ligation were
more likely to experience comorbidities. Rates of ligation-associated vocal cord
paralysis increased over time (1.2-3.9%); however, mortality decreased (12.4
6.5%). Thus, PDA ligation has become less frequent, although infants being
ligated are smaller and more medically complex. Despite increase in some
complications, mortality rates improved perhaps reflecting advances in care.
PMID- 29954593
TI - Twenty-first century cervical cancer management: A historical perspective of the
gynecologic oncology group/NRG oncology over the past twenty years.
AB - Since 1970, the Gynecologic Oncology Group (GOG) has been at the forefront of
evaluating and helping to implement ground breaking and paradigm changing
research in the management of cervical cancer. While the most dramatic example of
this impact was a series of clinical trials published in 1999 that evaluated
chemoradiation therapy versus radiation therapy alone for patients with various
clinical scenarios, including both locally advanced as well as post radical
hysterectomy patients, investigation has continued to further refine and improve
therapy. In 2014, based on the results of GOG protocol 240, bevacizumab became
the first approved targeted therapy in a gynecologic cancer in the United States.
Most recently, clinical trial work from the GOG is changing the standard of care
for all clinical scenarios. Finally, an emphasis on survivorship and special
populations are now top priorities.
PMID- 29954595
TI - Perspectives of cardiac rehabilitation staff on strategies used to assess,
monitor and review - a descriptive qualitative study.
AB - BACKGROUND: The mechanisms contributing to the success of cardiac rehabilitation
(CR) are poorly understood and may include assessment, monitoring and review
activities enabled by continuity of care and this is investigated in this study.
OBJECTIVES: To identify active assessment components of CR. METHODS: A
qualitative study using focus groups and individual interviews. CR staff (n = 39)
were recruited via professional association email and network contacts and
organised into major themes. RESULTS: CR staff assessment strategies and timely
actions undertaken provided a sophisticated post-discharge safety net for
patients. Continuity of care enabled detection of adverse health indicators, of
which medication issues were prominent. Interventions were timely and
personalised and therefore likely to impact outcomes, but seldom documented or
reported and thus invisible to audit. CONCLUSION: CR staff assessment and
intervention activities provide an unrecognised safety net of activities enabled
by continuity of care, potentially contributing to the effectiveness of CR.
PMID- 29954596
TI - Comparative analysis of endothelial cell and sub-endothelial cell elastic moduli
in young and aged mice: Role of CD36.
AB - OBJECTIVE: To perform comparative analysis of the role of scavenger receptor CD36
on endothelial vs. sub-endothelial elastic modulus (stiffness) in the aortas of
young and aged mice. APPROACHES AND RESULTS: Elastic moduli of endothelial and
sub-endothelial layers of freshly isolated mouse aortas were quantified using
atomic force microscopy. In young mice (4-6 months old), we found that while
endothelial stiffness is markedly reduced in aortas of CD36-/-mice, as compared
to WT controls, no difference between CD36-/- and WT aortas is observed in the
stiffness of the sub-endothelial layer in denuded arteries. Additionally,
inhibition of myosin phosphorylation also decreases the elastic modulus in the
EC, but not the sub-EC layer in WT mice. Moreover, inhibiting CD36 mediated
uptake of oxLDL in intact WT aortas abrogated oxLDL-induced endothelial
stiffening. Further analysis of aged mice (22-25 months) revealed that aging
resulted not only in significant stiffening of the denuded arteries, as was
previously known, but also a comparable increase in the elastic modulus of the
endothelial layer. Most significantly, this stiffening in the EC layer is
dependent on CD36, whereas the denuded layer is not affected. CONCLUSIONS: Our
results show that the role CD36 in stiffening of cellular components of intact
aortas is endothelial-specific and that genetic deficiency of CD36 protects
against endothelial stiffening in aged mice. Moreover, these data suggest that
endothelial stiffness in intact mouse aortas depends more on the expression of
CD36 than on the stiffness of the sub-endothelial layer.
PMID- 29954597
TI - Influence of forearm orientation on biceps brachii tendon mechanics and elbow
flexor force steadiness.
AB - Achilles tendon mechanics influence plantar flexion force steadiness (FS) and
balance. In the upper limb, elbow flexor FS is greater in supinated and neutral
forearm orientations compared to pronated, with contributions of tendon mechanics
remaining unknown in position-dependent FS. This study investigated whether
distal biceps brachii (BB) tendon mechanics across supinated, neutral and
pronated forearm orientations influence position-dependent FS of the elbow
flexors. Eleven males (23 +/- 3 years) performed submaximal isometric elbow
flexion tasks at low (5, 10% maximal voluntary contraction (MVC)) and high (25,
50, 75% MVC) force levels in supinated, neutral and pronated forearm
orientations. Distal BB tendon elongation and CSA were recorded on ultrasound to
calculate mechanics of tendon stress, strain and stiffness. Relationships between
FS, calculated as coefficient of variation (CV) of force, and tendon mechanics
were evaluated with multiple regressions. Supinated and neutral were ~50%
stronger and ~60% steadier than pronated (p < 0.05). Tendon stress was ~52%
greater in supinated and neutral compared to pronated, tendon strain was ~36%
greater in neutral than pronated (p < 0.05), while tendon stiffness (267.4 +/-
78.9 N/mm) did not differ across orientations (p > 0.05). At low forces, CV of
force was predicted by MVC (r2: 0.52) in supinated, and MVC and stress in neutral
and pronated (r2: 0.65-0.81). At high force levels, CV of force was predicted by
MVC and stress in supinated (r2: 0.49), and MVC in neutral (r2: 0.53). Absolute
strength and tendon mechanics influence the ability of the BB tendon to
distribute forces, and thus are key factors in position-dependent FS.
PMID- 29954599
TI - Effect of Prenatal Laterality Disturbance and Its Accompanying Anomalies on
Survival.
AB - In this retrospective, observational study of fetuses diagnosed with a laterality
disturbance we describe the findings and outcome of fetuses diagnosed between
1980 and 2017 at a tertiary fetal-pediatric cardiology unit. In addition we
sought to identify features which impact on outcome. Left atrial isomerism (LAI)
was diagnosed in 177 babies and right atrial isomerism (RAI) in 100. Major
structural heart disease was present in all cases of RAI and 91% with LAI.
Complete heart block (CHB) was present in 40% of LAI. For surviving live-born
infants a biventricular circulation was feasible in 3% with RAI and 43% with LAI.
The median survival for live-borns with LAI was 13 months (range 0 to 272 months)
and for RAI 19 months (range 0.3 to 292 months). The median postnatal survival
with CHB was 0.2 months (range 0 to 228 months) compared to 44 months with sinus
rhythm (interquartile range 0 to 272 months; p <0.0001). The 5-year survival was
1980 to 1989, RAI 0%, LAI 0%; 1990 to 1999, RAI 62%, LAI 54%; 2000 to 2009, RAI
59%, LAI 53%; 2010 to 2017, RAI 67%, LAI 75% by era. The rate of intrauterine
death remained. Risk factors for death/transplantation for RAI were total
anomalous pulmonary venous drainage, left heart obstruction (hazard ratios 2.7, p
= 0.048; 5.8, p = 0.03) and for LAI: CHB, anomalous pulmonary venous drainage and
right heart obstruction (hazard ratios 11.5, 6.2, 3.8, respectively (p = 0.008, p
= 0.003, p <0.001)). In conclusion, laterality disturbances represent a complex
form of congenital heart disease and although survival is improved, it remains
poor especially in the presence of anomalous pulmonary venous drainage, stenotic
and/or atretic valves, and CHB.
PMID- 29954598
TI - Management of skin, mucosa and joint involvement of Behcet's syndrome: A
systematic review for update of the EULAR recommendations for the management of
Behcet's syndrome.
AB - OBJECTIVES: The aim of this systematic review was to inform the update of
European League Against Rheumatism (EULAR) Recommendations for the management of
Behcet's syndrome (BS), on the evidence for the treatment of skin, mucosa and
joint involvement of BS. METHODS: A systematic literature search, data
extraction, statistical analyses and assessment of the quality of evidence were
performed according to a pre-specified protocol using the PRISMA guidelines.
Studies that assessed the efficacy of an intervention in comparison to an active
comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions,
nodular lesions or arthritis were included. Where possible, risk ratios were
calculated for binary outcomes and mean difference for continuous outcomes.
RESULTS: Among the 3927 references that were screened, 37 were included in the
analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint
involvement. Twenty-one of these studies were randomised controlled trials
(RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide,
etanercept and apremilast showed beneficial results with some differences
according to lesion type and gender. These agents were generally well tolerated
with few adverse events causing withdrawal from the study. CONCLUSIONS: RCTs
comprised more than a half (21/37, 57%) of the sources included in the evidence
synthesis related to skin, mucosa and joint involvement applicable for the EULAR
Recommendations for the management of BS. Differences in the outcome measures
that were used across the included studies often made it difficult to combine and
compare the results.
PMID- 29954600
TI - Comparison of Lipoprotein(a)-Levels in Patients >=70 Years of Age With Versus
Without Aortic Valve Stenosis.
AB - Although lipoprotein(a) (Lp[a]) is linked with aortic valve calcification and
clinical aortic valve stenosis (AVS) in middle-aged cohorts, patients aged >=70
years represent a majority of patients with AVS, in which mechanisms leading to
AVS may differ. We sought to determine whether Lp(a) distinguishes patients >=70
years with and without AVS. We matched 484 patients >=70 years with AVS,
scheduled for transcatheter aortic valve implantation with 484 patients without
AVS by age group and gender. Lp(a) levels were compared in patients with and
without AVS and stratified by presence and absence of clinical coronary artery
disease (CAD) manifestation. A total of 968 patients (mean age 80 +/- 5 years,
48% women) were included. When comparing patients with and without AVS, no
difference in Lp(a) was observed (AVS: 17 [8; 56] mg/dl, no AVS: 18.5 [8.5; 57]
mg/dl, p = 0.56). In contrast, patients with clinical CAD manifestation had
higher Lp(a) levels than those without clinical CAD manifestation (coronary
artery disease: 19 [9; 60] mg/dl, no coronary artery disease 15 [7; 44] mg/dl, p
= 0.0006). In regression analysis, no significant association of Lp(a) with AVS
was observed in unadjusted (OR [95% CI]: 0.98 [0.91 to 1.06], p = 0.59) and risk
factor-adjusted models (0.98 [0.90 to 1.06], p = 0.57). However, Lp(a) was
independently associated with clinical CAD manifestation (unadjusted: 1.14 [1.04
to 1.24], p = 0.003, risk factor adjusted: 1.17 [1.07 to 1.27], p = 0.0006). In
conclusion, in a large cohort of patients >=70 years, Lp(a) was associated with
clinical CAD manifesation, but not with AVS. Our results suggest that in patients
over 70 years, the development of AVS is not influenced by Lp(a).
PMID- 29954601
TI - Usefulness of Tilt Testing and Carotid Sinus Massage for Evaluating Reflex
Syncope.
AB - Thirty years ago Tilt Testing (TT) was described as a tool in the diagnostic work
up of vasovagal syncope; after its initial success, some flaws have become
evident. The concept of hypotensive susceptibility has provided the test a new
relevance, shifting from diagnosis only, to therapeutic management. Carotid Sinus
Massage (CSM) was introduced at the beginning of the XX century; the technique
has evolved over years, whereas the concept of carotid sinus syndrome (CSS) has
remained unchanged and uncontested for more than half a century. Nowadays, CSS is
a matter of debate, with new classifications and criteria coming on the scene.
Recently, a common central etiological mechanism has been hypothesized for reflex
syncope, manifesting as CSS, vasovagal syncope or both. In this context, TT and
CSM acquire an important role in clinical practice, being essential for a
complete diagnosis and treatment. Recalling their historical background, the
present paper illustrates an actual interpretation of TT and CSM.
PMID- 29954602
TI - Corrigendum to 'Histone methyltransferase SETD2 regulates osteosarcoma cell
growth and chemosensitivity by suppressing Wnt/beta-catenin signaling' [Biochem.
Biophys. Res. Commun. Volume 502, Issue 3, 20 July 2018, Pages 382-388].
PMID- 29954603
TI - Corrigendum to "Luciferase of the Japanese syllid polychaete Odontosyllis
undecimdonta" [Biochem. Biophys. Res. Commun. 2018 Jul 20;502(3):318-323].
PMID- 29954605
TI - Delayed Cord Clamping in Infants with Suspected Intrauterine Growth Restriction.
AB - : We evaluated a subset of infants with suspected intrauterine growth restriction
or birth weights small for gestational age enrolled in a study of delayed cord
clamping for preterm infants. Compared with immediate clamping, delayed cord
clamping was associated with no apparent harm and less suspected necrotizing
enterocolitis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00818220 and
NCT01426698.
PMID- 29954604
TI - Respiratory Compliance in Late Preterm Infants (340/7-346/7 Weeks) after
Antenatal Steroid Therapy.
AB - OBJECTIVE: To compare respiratory compliance in late preterm infants (340/7-346/7
weeks) who received antenatal steroids vs matched late preterm infants who did
not receive antenatal steroids. STUDY DESIGN: This was a single-center
prospective cohort study. Patients were matched for birth weight, gestational
age, race, and sex. Respiratory compliance was the primary outcome measured with
the single breath occlusion technique. RESULTS: We studied 25 late preterm
infants treated with antenatal steroids and 25 matched infants who did not
receive antenatal steroids. The treated infants had a significantly increased
respiratory compliance/kg (adjusted 95% CI 0.05, 0.49; P = .016) and fewer
required continuous positive airway pressure (P = .007) or >24 hours of
supplemental oxygen (P = .046). There was no difference in surfactant therapy.
CONCLUSIONS: Respiratory compliance was significantly increased in this cohort of
late preterm infants born at 340/7-346/7 weeks who received antenatal steroids
compared with matched infants who did not receive antenatal steroids. Although
not randomized, these data provide physiologic support for the possible
beneficial effects of antenatal steroids in late preterm infants.
PMID- 29954606
TI - The Effect of Noninvasive High-Frequency Oscillatory Ventilation on Desaturations
and Bradycardia in Very Preterm Infants: A Randomized Crossover Trial.
AB - : Noninvasive high-frequency oscillatory ventilation compared with nasal
continuous positive airway pressure significantly reduced the number of
desaturations and bradycardia in preterm infants. However, noninvasive high
frequency oscillatory ventilation was associated with increased oxygen
requirements and higher heart rates. TRIAL REGISTRATION: Australian and New
Zealand Clinical Trial Registry: ACTRN12616001516471.
PMID- 29954607
TI - Wandering Liver, Wondering Doctors!
PMID- 29954608
TI - Deep Palmar and Plantar Creases in Costello Syndrome.
PMID- 29954609
TI - Population-Based Validation of a Clinical Prediction Model for Congenital
Diaphragmatic Hernias.
AB - OBJECTIVE: To examine the external validity of a well-known congenital
diaphragmatic hernia (CDH) clinical prediction model using a population-based
cohort. STUDY DESIGN: Newborns with CDH born in California between 2007 and 2012
were extracted from the Vital Statistics and Patient Discharge Data Linked Files.
The total CDH risk score was calculated according to the Congenital Diaphragmatic
Hernia Study Group (CDHSG) model using 5 independent predictors: birth weight, 5
minute Apgar, pulmonary hypertension, major cardiac defects, and chromosomal
anomalies. CDHSG model performance on our cohort was validated for discrimination
and calibration. RESULTS: A total of 705 newborns with CDH were extracted from 3
213 822 live births. Newborns with CDH were delivered in 150 different hospitals,
whereas only 28 hospitals performed CDH repairs (1-85 repairs per hospital). The
observed mortality for low-, intermediate-, and high-risk groups were 7.7%,
34.3%, and 54.7%, and predicted mortality for these groups were 4.0%, 23.2%, and
58.5%. The CDHSG model performed well within our cohort with a c-statistic of
0.741 and good calibration. CONCLUSIONS: We successfully validated the CDHSG
prediction model using an external population-based cohort of newborns with CDH
in California. This cohort may be used to investigate hospital volume-outcome
relationships and guide policy development.
PMID- 29954610
TI - Preparation of ionic liquid hybrid melamine-based covalent organic polymer
functionalized polymer monolithic material for the preconcentration of synthetic
phenolic antioxidants.
AB - In this study, a hybrid composite containing melamine-based covalent organic
polymer (MCOP) and ionic liquid (IL) was designed and employed for the
functionalization of polymer monolith. The obtained polymer monolithic material
was confirmed by scanning electron microscopy, Fourier-transformed infrared
spectroscopy, X-ray photoelectron spectroscopy, and thermal gravimetric analysis.
A polymer monolith microextraction (PMME) strategy was established based on the
monolith for the enrichment of synthetic phenolic antioxidants, exhibiting high
sensitivity, good stability and repeatability. Intra-day and inter-day relative
standard deviations were both less than 10%. The developed PMME-HPLC method was
applied to the preconcentration and determination of synthetic phenolic
antioxidants in cosmetic samples and assessed through recovery studies. The
developed polymer monolithic material had great potential as a candidate in the
preconcentration field for PMME.
PMID- 29954611
TI - Chiral gas chromatography of 2,5-diketopiperazines following a ring-opening
derivatization method for complete isomeric separation.
AB - 2,5-Diketopiperazines (DKPs) are widely recognized as chiral molecules with great
potential in medicinal chemistry. Complete separation of DKP stereoisomers is
very important for efficiently investigating the chemical characteristics of
DKPs. The combination of esterification and acylation caused the enantiomers of
cyclo(d-Ala-d-Ala) and cyclo(l-Ala-l-Ala) to ring-open and generate their
dipeptide derivatives. These derivatives were completely separated by chiral gas
chromatography (GC), and the determined isomer ratios were the same as the
original isomer ratios. The derivatization also caused the ring-opening of
cyclo(l-Asp-l-Phe) and cyclo(l-Met-l-Pro), and their derivatives were determined
by the chiral GC method. The present study is the first report of the complete
separation of cis-DKPs using chiral GC. This separation procedure can
substantially contribute to the development of the chemistry of chiral DKPs.
PMID- 29954612
TI - The utility of PHQ-9 and CGI-S in measurement-based care for predicting suicidal
ideation and behaviors.
AB - BACKGROUND: Measurement-based care (MBC) has emerged as an effective strategy for
improving outcomes in patients with mood disorders. Suicide is a particularly
devastating outcome of mood disorders. Using data from a new MBC program from the
National Network of Depression Centers (NNDC), we examined whether capturing a
patient-rated symptom measure, the patient health questionnaire (PHQ-9), along
with a provider-rated global functioning measure, the clinical global impression
scale (CGI-S), improves identification of patients at risk of suicide over using
either measure alone. METHODS: A total of 126 adults with mood disorders from
nine sites in the NNDC completed the PHQ-9 and CGI-S and had at least one
subsequent visit where they completed the Columbia-suicide severity rating scale
(C-SSRS). The PHQ-9 (>=10) and CGI-S (>=4) were dichotomized at commonly accepted
severity thresholds. Associations of the PHQ-9 and CGI-S with suicidal ideation
or behavior were examined using Firth's logistic regression to accommodate small
samples while controlling for age, sex, race, and diagnosis. RESULTS: Patients
who scored higher on only the PHQ-9 or CGI-S were not significantly more likely
to experience subsequent suicidal ideation or behaviors. However, patients who
scored higher on both the PHQ-9 and CGI-S were significantly more likely to
experience suicidal ideation (OR = 4.70, p = 0.0005) and suicidal behaviors (OR =
25.38, p = 0.0003). DISCUSSION: Information from both patient and clinician-rated
measures was better able to identify patients with mood disorders at risk for
suicidal ideation and behaviors. Using both together may help reduce the risk of
suicide by identifying those patients at greatest risk and allowing for more
targeted interventions.
PMID- 29954613
TI - Graphene-like Metal-Free 2D Nanosheets for Cancer Imaging and Theranostics.
AB - The great success of graphene has driven the discovery and development of new 2D
nanomaterials with different optical, electrical, and thermal properties.
Compared with other graphene-like 2D nanomaterials, metal-free 2D nanomaterials
hold great potential in biomedical applications since they exhibit much better
biocompatibility and biosafety. We give an overview of some rapidly emerging
graphene-like metal-free 2D nanomaterials including black phosphorus, hexagonal
boron nitride, and graphitic carbon nitride, as well as 2D organic polymer-based
nanomaterials, and highlight their impressive advances for bioimaging and cancer
theranostics in recent years. The challenges and some thoughts on future
perspectives in this field are also addressed.
PMID- 29954614
TI - Corrigendum re: "The Impact of Prostate Size, Median Lobe, and Prior Benign
Prostatic Hyperplasia Intervention on Robot-Assisted Laparoscopic Prostatectomy:
Technique and Outcomes" [Eur Urol 2011;59:595-603].
PMID- 29954615
TI - The role of trust in public attitudes toward invasive species management on Guam:
A case study.
AB - Public attitudes toward invasive alien species management and trust in managers'
ability to effectively manage non-native species can determine public support for
conservation action. The island of Guam has experienced widespread species loss
and ecosystem transformation due to invasive species, most notably, the brown
treesnake (Boiga irregularis). Despite Guam's long history with invasives and
extensive efforts to eradicate them, we know little about the sociological
context of invasive species and drivers of public support or opposition on the
island. Using focused group discussions, we explore public attitudes toward
invasive species management measures. Respondents were familiar with the common
invasive species on Guam and recognized that they were not native. They expressed
support for management activities, interest in more effective and frequent
management initiatives, and desire to participate directly in conservation
actions. Participants also expressed frustration with government institutions and
lack of confidence in managers' ability to control invasive species. Perceptions
of managers' trustworthiness, communication with managers, and positive personal
experiences with managers were related to positive attitudes about management and
support for existing initiatives, indicating the important role of trust and
engagement for invasive species management.
PMID- 29954616
TI - [Clinical, radiological, pathological features, treatment and follow-up of
periocular and/or orbital amyloidosis: Report of 6 cases and literature review].
AB - PURPOSE: To assess demographic, clinical, radiological, pathological features,
treatment and follow-up of periocular or/and orbital amyloidosis. PATIENTS AND
METHODS: We conducted an observational retrospective monocentric study from
January 2004 to April 2017 in patients diagnosed with histologically proven
periocular or/and orbital amyloidosis. RESULTS: Six patients were included (2
females, 4 males). Mean age was 76.8 years (range 66-88 years). Mean time between
first ophthalmological symptoms and diagnosis was 27 months (range 11-36 months).
The main symptoms were subconjunctival infiltration (6 patients; 100%),
periocular pain or discomfort (4 patients; 66.6%) and subconjunctival hemorrhage
(1 patient; 16.6%). Clinical findings included ptosis (4 patients; 66.6%),
keratitis (3 patients; 50%) leading to corneal perforation in one patient, and
proptosis (3 patients; 50%). One-half of the patients showed bilateral
involvement. AL amyloidosis was identified on immunohistochemistry in 5 patients
(83.3%). One case of B cell marginal zone orbital lymphoma was diagnosed.
Systemic work-up was negative for all patients. Treatment consisted of simple
monitoring (1 patient; 16.6%), surgical debulking (3 patients; 50%), ptosis
surgery (1 patient; 16.6%), eyelid or eyelash malposition surgery (2 patients;
33.3%) and orbital radiation beam therapy (2 patients; 33.3%). Mean follow-up was
14.6 months (range 6-36 months), and no progression nor recurrence were noted.
CONCLUSION: Periocular or/and orbital amyloidosis is rarely encountered.
Diagnosis is based on pathological examination, and immunohistochemistry analysis
should always be performed to guide systemic work-up. Orbital lymphoma and
multiple myeloma should be ruled out if AL amyloidosis is diagnosed. Progression
is slow, and surgery is the mainstay of treatment in symptomatic patients. Long
term multidisciplinary follow-up is advocated.
PMID- 29954617
TI - Corrigendum to "Biouptake, toxicity and biotransformation of triclosan in diatom
Cymbella sp. and the influence of humic acid" [Environ. Pollut. 234 (2018) 231
242].
PMID- 29954618
TI - Functional and histologic effects after implanting pluripotent stem cells in a
murine model with sphincterotomy.
AB - INTRODUCTION AND AIMS: Fecal incontinence is a disabling condition with
devastating consequences for the patients. Medical and surgical options are not
very satisfactory, reason by which regenerative medicine has been considered in
this field. In the present research, we analyzed functional and histologic
effects after implanting pluripotent stem cells (PSCs) in a murine model with
sphincterotomy. MATERIALS AND METHODS: Female Wistar rats were subjected to
sphincterotomy and divided into three groups. Group 1 (control group) was treated
with 300MUL of balanced saline solution and group 2 (late treatment) and group 3
(early treatment) received 50,000 PSCs resuspended in 300MUL of balanced saline
solution. All animals were evaluated through high-resolution anorectal manometry
24hours before and after sphincterotomy and every month for three months.
Finally, the rats were euthanized and histopathologic sections from the anal
canal were obtained. RESULTS: All groups showed a decrease in resting anal
pressure and squeeze anal pressure 24hours after sphincterotomy. At the third
month, higher anal pressures in the groups treated with PSCs were detected.
Regarding the histologic effects, the microscopic architecture was restored and
there was a significant decrease in the inflammatory response in the groups
treated with PSCs. CONCLUSION: PSCs implantation improves anal tone, as well as
histologic structure, presenting better regenerative results when implanted as
early treatment.
PMID- 29954619
TI - New microperforated pure titanium membrane created by laser processing for guided
regeneration of bone.
PMID- 29954620
TI - The wide distribution of an extremely thermoacidophilic microorganism in the
copper mine at ambient temperature and under acidic condition and its
significance in bioleaching of a chalcopyrite concentrate.
AB - Thermoacidophiles can exist in a state of dormancy both in moderate temperatures
and even in cold conditions in heap leaching. Sulphide mineral ores such as
chalcopyrite produce sulfuric acid when exposed to the air and water. The
produced sulfuric acid leads to the decrease of pH and exothermic reactions in
heap leaching causing the temperature to increase up to 55 degrees C and the
activation of thermoacidophilic microorganisms. The aim of the present study was
to isolate indigenous extreme thermoacidophilic microorganisms at ambient
temperature from Sarcheshmeh Copper Complex, to adapt them to the high pulp
density of a chalcopyrite concentrate, and to determine their efficiency in
chalcopyrite bioleaching in order to recover copper. In this study samples were
collected at ambient temperature from Sarcheshmeh Copper Complex in Iran. Mixed
samples were inoculated into the culture medium for enrichment of the
microorganisms. Pure cultures from these enrichments were obtained by subculture
of liquid culture to solid media. Morphological observation was performed under
the scanning electron microscope. Isolates were adapted to 30% (w/v) pulp
density. For the bioleaching test, the experiments were designed with DX7
software. Bioleaching experiments were carried out in Erlenmeyer flasks and a
stirred tank reactor. The highest copper recovery in Erlenmeyer flasks was 39.46%
with pulp 15%, inoculums 20%, size particle 90MUm and 160rpm. The lowest recovery
was 3.81% with pulp 20%, inoculums 20%, size particle 40MUm and 140rpm after 28
days. In the reactor, copper recovery was 32.38%. Bioleaching residues were
analyzed by the X-ray diffraction (XRD) method. The results showed no jarosite
(KFe3(SO4)2(OH)6) had formed in the bioleaching experiments. It seems that the
antagonistic reactions among various species and a great number of planktonic
cells in Erlenmeyer flasks and the stirred tank reactor are the reasons for the
low recovery of copper in our study.
PMID- 29954621
TI - Properdin: A multifaceted molecule involved in inflammation and diseases.
AB - Properdin, the widely known positive regulator of the alternative pathway (AP),
has undergone significant investigation over the last decade to define its
function in inflammation and disease, including its role in arthritis, asthma,
and kidney and cardiovascular diseases. Properdin is a glycoprotein found in
plasma that is mainly produced by leukocytes and can positively regulate AP
activity by stabilizing C3 and C5 convertases and initiating the AP. Promotion of
complement activity by properdin results in changes in the cellular
microenvironment that contribute to innate and adaptive immune responses,
including pro-inflammatory cytokine production, immune cell infiltration, antigen
presenting cell maturation, and tissue damage. The use of properdin-deficient
mouse models and neutralizing antibodies has contributed to the understanding of
the mechanisms by which properdin contributes to promoting or preventing disease
pathology. This review mainly focusses on the multifaceted roles of properdin in
inflammation and diseases, and how understanding these roles is contributing to
the development of new disease therapies.
PMID- 29954622
TI - Ovarioleukodystrophy: Vanishing white matter versus AARS2-related
ovarioleukodystrophy.
PMID- 29954623
TI - Acute myocardial infarction in a patient with a recent diagnosis of Crohn's
disease.
PMID- 29954624
TI - Retinoblastoma: The importance of early diagnosis.
AB - INTRODUCTION: Retinoblastoma is the most frequent malignant intraocular tumour in
childhood, and both its cure and the sequelae arising from it, mainly depend on
an early diagnosis. There is currently no consensus on its diagnostic and
therapeutic management. PATIENTS AND METHODS: A descriptive, retrospective, and
non-randomised study was conducted on a series of cases (39 patients -58 eyes),
treated during the period 2006-2013, in the Regional Reference Centre for Tumours
of the National Health Service Quality Agency. RESULTS: The most frequent
presentation sign is leukocoria (71.8%), followed by strabismus (17.9%). All
cases of bilateral tumour had a germline mutation of the RB1 gene, and 20% had a
family history. Stage E was observed in 55% of the patients, and 90% required
chemotherapy treatment. The eye was maintained in 57% of those who had mild
stages, compared to 43% who maintained it in advanced stages. CONCLUSIONS: This
analysis included 58 eyes. There are no previous studies in our community and
there are few series so numerous throughout the country. Based on non
standardised treatment, the most appropriate is chosen according to the
characteristics of the tumour. The multidisciplinary management, formed by
ophthalmology, paediatric oncology, radiotherapy, and radiophysical oncology, is
fundamental for the selection of the most appropriate treatment. Chemo-reduction,
along with consolidation treatments, offers encouraging results in the control of
these tumours, especially in those of less severity. Enucleation continues to be
the method of choice in the most advanced staging with vitreous involvement, with
the importance of early diagnosis being highlighted.
PMID- 29954625
TI - Is Toxoplasma gondii playing a positive role in multiple sclerosis risk? A
systematic review and meta-analysis.
AB - Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii with a globally
widespread distribution. The aim of this systematic review and meta-analysis was
to characterize the association between T. gondii infection and multiple
sclerosis (MS). The data were systematically collected from the English
electronic databases up to April 2017. The research process resulted in the
identification of five studies related to the subject of interest entailing 669
MS patients and 770 controls. The pooled prevalence rates of T. gondii infection
in the MS patients and controls were estimated as 32.4% (95% CI: 27.4-38.6) and
39.1% (95% CI: 29.1-50.5), respectively. By random effect model, the combined
odds ratio was 0.72 (95% CI: 0.49-1.06) with P = .0961. Although this meta
analysis study showed a lower seroprevalence of T. gondii in the MS patients as
compared with that in the control group, no significant association was found
between toxoplasmosis and MS disease. Further investigations are recommended to
determine the detailed association between MS patients and T. gondii infection.
PMID- 29954627
TI - A student midwife's perspective from Australia.
PMID- 29954626
TI - Toll-like receptors 4, 5, 6 and 7 are constitutively expressed in non-human
primate retinal neurons.
AB - The purpose of this study was to characterize cell-specific expression patterns
of Toll-like receptors (TLR) in non-human primate (NHP) neural retina tissue. TLR
4, 5, 6, and 7 proteins were detected by immunblotting of macaque retina tissue
lysates and quantitative PCR (qPCR) demonstrated TLRs 4-7 mRNA expression.
Immunofluorescence (IF) microscopy detected TLRs 4-7 in multiple cell types in
macaque neural retina including Muller, retinal ganglion cells (RGC), amacrine,
and bipolar cells. These results demonstrate that TLRs 4-7 are constitutively
expressed by neurons in the NHP retina raising the possibility that these cells
could be involved in retinal innate inflammatory responses.
PMID- 29954628
TI - Insulin Dependence Is Associated With Increased Risk of Complications After Upper
Extremity Surgery in Diabetic Patients.
AB - : Diabetes mellitus (DM) is associated with the development of carpal tunnel
syndrome, Dupuytren disease, trigger digits, and limited joint mobility. Despite
descriptions of poorer response to nonsurgical treatment, previous studies have
not shown increased complication rates in diabetic patients after hand surgery.
Few studies, however, differentiate between insulin-dependent (IDDM) and non
insulin-dependent (NIDDM) diabetes mellitus. The purpose of this study was to
evaluate the impact of insulin dependence on the postoperative risk profile of
diabetic patients after hand surgery using a national database. MATERIALS AND
METHODS: The data were obtained through the National Surgical Quality Improvement
Program (NSQIP) database. Patients undergoing surgery from the distal humerus to
the hand, between 2005 and 2015, were identified using 297 distinct Current
Procedural Terminology codes. Thirty-day postoperative complications were
collected and categorized into medical complications, surgical site
complications, and readmission. Surgical complications, medical complications,
and readmissions were compared between patients with NIDDM or IDDM to those
without DM using multivariable logistic regression, adjusting for baseline
patient and operative characteristics. RESULTS: The study cohort included 52,727
patients. Patients with IDDM had a 5.7% overall complication rate compared with
2.3% and 1.5% in NIDDM and nondiabetic patients, respectively. After controlling
for differences in patient and surgical characteristics, patients with IDDM had a
statistically significant increased rate of any complication, surgical site
complications, superficial surgical site infections, and readmission. There was
no significant difference in complication rates between patients with NIDDM and
nondiabetic patients. CONCLUSIONS: Our data demonstrate a greater risk of
complications following hand and upper extremity surgery for patients with IDDM,
specifically surgical site infections. The NIDDM patients did not have an
increased rate of complications relative to nondiabetic patients. These findings
are important for patient risk stratification and may guide further investigation
to decrease complication rates in IDDM patients after upper extremity surgery.
TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.
PMID- 29954629
TI - Contributory behaviors and life satisfaction among Chinese older adults:
Exploring variations by gender and living arrangements.
AB - The rapid population aging taking place in China makes studies tackling
opportunities associated with aging an urgent priority. Based on the productive
aging perspective, this study examines the relationship between contributory
behaviors (i.e., providing economic, housework, and emotional support to adult
children and providing care for grandchildren) and life satisfaction, as well as
how gender and living arrangements modify the relationship. Using data collected
from 809 older adults in Wuhan, China, and applying ordinary least squares
regressions, this study found that engaging in contributory behaviors in general,
and providing emotional support to adult children and caring for grandchildren in
particular, are associated with enhanced life satisfaction. The association
between caring for grandchildren and life satisfaction is only salient for males
but not for females. For living arrangements, the positive association between
engaging in contributory behaviors and life satisfaction is only identified among
older adults living with their spouse and other family members. The positive
association of providing emotional support to adult children with life
satisfaction is significant for older adults living with their spouse only.
Finally, frequently taking care of grandchildren is related positively to life
satisfaction among those living with both spouse and other family members. Our
findings provide empirical evidence suggesting that Chinese older adults are
still very active in providing support to family members and highlight the
beneficial effects of contributory behaviors on individual's life satisfaction.
For policy makers, it is important to continuously promote values of contributing
behaviors to family and take into account the importance of family ties and
family support to older adults when designing new elder care programs.
PMID- 29954630
TI - Prevention of meningococcal disease at mass gatherings: Lessons from the Hajj and
Umrah.
AB - Meningococcal disease is a serious public health threat given the seriousness of
the illness, its disabling sequelae and its potential for epidemic spread. The
disease is a concern during mass gatherings which provide conditions that
facilitate transmission of infectious agents including Neisseria meningitidis.
Implementation of appropriate meningococcal disease preventive measures during at
risk mass gatherings is crucial to prevent illness and outbreaks which may result
in significant morbidity and mortality as well as local and international spread
of the disease. These preventive measures should be informed by comprehensive
risk assessments of the disease at those events and may include the use of
vaccination, chemoprophylaxis and health awareness and educational campaigns,
supported by efficient disease surveillance and response systems. The Hajj and
Umrah religious mass gatherings in the Kingdom of Saudi Arabia are examples of
how the implementation of such preventive measures was successful in reducing the
incidence of meningococcal disease during these events as well as controlling and
preventing outbreaks. Lessons learned from the Hajj and Umrah experience can
inform meningococcal disease preventive strategies for other mass gatherings
worldwide.
PMID- 29954631
TI - Genetic and neuroattenuation phenotypic characteristics and their stabilities of
SA14-14-2 vaccine seed virus.
AB - Japanese encephalitis (JE) live attenuated vaccine SA14-14-2 is the most widely
used JE vaccine in the world. Large-scale clinical trials have demonstrated
satisfactory safety and efficacy profiles. The establishment of genetic and
attenuated neurovirulence characteristics and their stabilities of SA14-14-2
virus are important in relation to vaccine safety in humans. Therefore, several
researchers have studied and analyzed the full-length gene sequences of the SA14
14-2 virus strain. However, sequencing results have shown a significant
difference. Here, we further studied the full-length sequence of three class seed
virus banks of the vaccine as well as two vaccine viruses with different passages
in primary hamster kidney cells, and compared them with our original stored SA14
parent virus (low passage in mouse brain). The full-length gene sequence
determined in this study indicates there were 57 nucleotide and 25 amino acid
substitutions of the SA14-14-2 strain compared to its parental SA14 virus strain.
The full-length sequences of the three class seed bank viruses and the vaccine
virus PHKC8 were completely identical among them, but the working seed virus
passaged in primary hamster kidney cells for 17 generations (PHKC17) had a single
nucleotide change at the 5' NCR. Both KM and ICR mice tested by intracerebral
(i.c.) or subcutaneous (s.c.) routes with the three class seed viruses and
vaccine viruses with >=5.7 lgpfu/mL remained healthy, but all the mice inoculated
with the SA14 parental virus strain died as early as day 5 post-inoculation. The
present study provided new information on the full-length gene sequence and
attenuated neurovirulence of SA14-14-2. They can be used as a reference sequence
for vaccine quality control and surveillance of neurovirulence reversion
following vaccination. Moreover, the present results further demonstrated the
high genetic and phenotypic stabilities of the SA14-14-2 virus, suggesting the
neurovirulence reversion of the vaccine strain will be highly unlikely.
PMID- 29954632
TI - Commercial cannabis consumer products part 1: GC-MS qualitative analysis of
cannabis cannabinoids.
AB - The recent surge in the sale of cannabis-based consumer products in the US
includes foods, candies, beverages, topicals, vapes/eliquids, oral supplements in
various forms, recreational marijuana plants, and plant extracts or preparations.
The wide variety of product and sample types has resulted in a host of new matrix
interferences when conducting qualitative testing for the cannabis cannabinoids
such as cannabidiol and d9-tetrahydrocannabinol. A qualitative GC-MS method is
presented in this work, which uses a commercial 35% silphenylene phase to provide
chromatographic resolution for 11 target cannabinoids as their trimethylsilyl
derivatives (CBD, CBDA, d9THC, THCA, CBN, d8THC, CBG, CBGA, CBDV, THCV, and CBC).
The method uses variants of ethanol- and acetonitrile-based extractants to
successfully minimize or eliminate several types of interferents, and also
provides protocols to address specific interferents such as glycerin and lactose.
Method validation included spike/recovery for five cannabinoids of primary
interest (spiking level 50MUg/g) from a series of edible oils, foods, beverages,
candies, topicals, oral OTC pharmaceuticals, glycerin, and propylene glycol. The
minimum detectable concentration was established as 1.0MUg/g. The method was
applied to about sixty diverse commercial products, as well as to recreational
marijuana plants, plant preparations, hempseed oils, and dronabinol capsules.
PMID- 29954633
TI - A comparison of different surfactants on foam stability in foam sclerotherapy in
vitro.
AB - OBJECTIVE: This article compares the effect of different surfactants on foam
stability and determines the foam decay relationship, so that the suitability of
surfactants in a clinical setting can be evaluated. METHODS: Five different
surfactants were used to prepare sclerosing foam at room temperature using a
liquid:gas ratio of 1:4 in vitro. Foam decay experiments were performed for each
sample using a laboratory-made foaming apparatus, and the process was recorded
using a video camera. The stability indices used included the drainage time,
drainage rate, half-life, foam half-life volume, surfactant stability index, and
foaming index. RESULTS: The sodium morrhuate foam was relatively more stable than
the polidocanol foam, but exhibited weak foaming. After the addition of the
surfactants, the foam half-life was less than 300 seconds. The effect of the
surfactants on the stability of the sodium morrhuate foam was more pronounced.
The surfactant stability indices could be arranged as follows: poloxamer 188 >
Tween 80 > macrogol 4000 > propanediol > lecithin. However, the differences in
the foaming indices were small. CONCLUSIONS: Of the five surfactants tested,
poloxamer 188 has best performance to enhance sclerosing foam stability. The
addition of the surfactants improved the stability of the sclerosing foams. It
was observed that the relationships between the foam half-life and the surfactant
stability index and the surfactant concentration follow the power law.
PMID- 29954634
TI - The Effect of Signed-Out Emergency Department Patients on Resident Productivity.
AB - BACKGROUND: Transitions of care and patient hand-offs between physicians have
important implications for patient care. However, what effect caring for signed
out patients has on providing care to new patients and education is unclear.
OBJECTIVE: We sought to determine whether the number of patients a physician
receives in sign-out affects productivity. METHODS: This was a retrospective
cohort study, conducted at an emergency medicine residency program. A general
estimation equation was constructed to model productivity, defined as new
patients evaluated and relative value units (RVUs) generated per shift, relative
to the number of sign-outs received, and training year. A secondary analysis
evaluated the effect of signed-out patients in observation. RESULTS: We evaluated
19,389 shifts from July 1, 2010 to July 1, 2017. Postgraduate year (PGY)-1
residents without sign-out evaluated 10.3 patients (95% confidence interval [CI]
9.83 to 10.7), generating 31.6 RVUs (95% CI 30.5 to 32.7). Each signed-out
patient was associated with -0.07 new patients (95% CI -0.12 to -0.01), but no
statistically significant decrease in RVUs (95% CI -0.07 to 0.28). PGY-2
residents without sign-out evaluated 13.6 patients (95% CI 12.6 to 14.6),
generating 47.7 RVUs (95% CI 45.1 to 50.3). Each signed-out patient was
associated with -0.25 (95% CI -0.40 to -0.10) new patients, and -0.89 (95% CI
1.22 to -0.55) RVUs. For all residents, observation patients were associated with
more substantial decreases in new patients (-0.40; 95% CI -0.47 to -0.33) and
RVUs (-1.11; 95% CI -1.40 to -0.82). CONCLUSIONS: Overall, sign-out burden is
associated with a small decrease in resident productivity, except for observation
patients. Program faculty should critically examine how signed-out patients are
distributed to address residents' educational needs, throughput, and patient
safety.
PMID- 29954635
TI - Extranasopharyngeal angiofibroma mimicking choanal polyp in patients with chronic
paranasal sinusitis.
AB - Extranasopharyngeal angiofibroma (ENA) is an angiofibroma that occurs in the
extranasopharynx. It shows pathologic findings, such as juvenile angiofibroma
(JNA), which accounts for 0.5% of head and neck mass. However, compared with JNA,
the prevalence, affected site, and clinical characteristics are completely
different, which leads some physicians to classify ENA as a disease different
from JNA. ENA of the nasal turbinate origin are rarely reported in the
literature. In addition, choanal polyp originating from the posterior part of the
nasal turbinate is uncommonly reported. Recently, we encountered two cases of
ENA, which were not diagnosed by intraoperative frozen section examination, but
were histopathologically diagnosed post-operatively. Although we were unable to
diagnose and perform embolization pre-operatively, ENA has been successfully
treated by endoscopic surgery, without profuse bleeding.
PMID- 29954636
TI - Binaural sensitivity to temporal fine structure and lateralization ability in
children with suspected (central) auditory processing disorder.
AB - OBJECTIVE: Previous studies have shown that a subgroup of children with suspected
(central) auditory processing disorder (SusCAPD) have insufficient ability to use
binaural cues to benefit from spatial processing. Thus, they experience
considerable listening difficulties in challenging auditory environments, such as
classrooms. Some researchers have also indicated the probable role of binaural
temporal fine structure (TFS) in the perceptual segregation of target signal from
noise and hence in speech perception in noise. Therefore, in the present study,
in order to further investigate the underlying reason for listening problems
against background noise in this group of children, their performance was
measured using binaural TFS sensitivity test (TFS-LF) as well as behavioral
auditory lateralization in noise test, both of which are based on binaural
temporal cues processing. METHODS: Participants in this analytical study included
91 children with normal hearing and no listening problems and 41 children (9-12
years old) with SusCAPD who found it challenging to understand speech in noise.
Initially, the ability to use binaural TFS was measured at three frequencies
(250, 500 and 750Hz) in both the groups, and the results of preliminary
evaluations were compared between normal children and those with SusCAPD who
participated in the study. Thereafter, the binaural performance of the 16
children with SusCAPD who had higher thresholds than the normal group at all
three frequencies tested in TFS-LF test was examined using the lateralization
test in 7 spatial locations. RESULTS: Total 16 of the 41 children with SusCAPD
who participated in this study (39%) showed poor performance on the TFS-LF test
at all three frequencies, compared to both normal children and other children in
the APD group (p<0.05). Furthermore, children in the APD group with binaural TFS
coding deficits at all three frequencies revealed significant differences in the
lateralization test results compared to normal children (p<0.05). CONCLUSION:
Findings of the current study demonstrated that one of the underlying causes for
the difficulty understanding speech in noisy environments experienced by a
subgroup of children with SusCAPD can be the reduced ability to benefit from
binaural TFS information. This study also showed that a reduced ability to use
binaural TFS cues in the group of children with SusCAPD was accompanied by
reduced binaural processing abilities in the lateralization test which also admit
the presence of binaural temporal processing deficits in this group of children.
PMID- 29954637
TI - [Maternal smoking during pregnancy: A risk factor for respiratory disorders in
children].
AB - Maternal smoking during pregnancy (MSDP) is a well-established risk factor for
negative pregnancy outcomes, but its negative effects on the health of the child
after birth are less well known by both health professionals and the general
public. Large cohort studies over the past 10 years have shown that MSDP is an
independent risk factor for several childhood health problems such as e.g.
obesity and smoking. A large number of recent studies and 3 meta-analyses
demonstrate that MSDP is an independent risk factor of wheezing and asthma of the
child exposed in utero to maternal smoking. MSDP is associated with epigenetic
toxicities the currently most plausible hypothesis to explain the diversity of
its postnatal negative effects. The eradication of MSDP could contribute to the
reduction of health problems in the next generation, including the incidence of
childhood respiratory disorders.
PMID- 29954638
TI - Inflammatory Breast Cancer: What surgeons need to know.
AB - Strict criteria to identify Inflammatory Breast Cancer (IBC) have been made
available - these are based on pathological as well as clinical observations. It
is mandatory to confirm the criteria used in any further report. Scientific
evidence accumulated so far is confusing, and unclear therefore no hard
conclusion can be drawn from the available literature on the management of IBC.
The advent of new medications results into an up-to-date management and different
outcomes. It is mandatory to follow these criteria if reliable guidelines are to
be made available in the next future.
PMID- 29954639
TI - The HPB controversy of the decade: 2007-2017 - Ten years of ALPPS.
AB - Ten years ago the first patient underwent Associating Liver Partition and Portal
Vein Ligation for Staged Hepatectomy (ALPPS). This report aimed to critically
review literature on ALPPS in terms of methods, outcomes, and bias. In total, 237
English papers on ALPPS were identified, 75 (32%) were letters and 43 (18%) case
reports. Forty-nine single-center series reported a median 10 patients, with 0
69% morbidity and 0-50% mortality. The indications for ALPPS were reported in 35%
and 47% reported on modifications. Twenty-three multicenter series included a
median 45 patients. Some reports excluded up to 399 cases. 26% reported on the
indications and 35% on ALPPS modifications. Across journals, variation in
positive and negative conclusions on ALPPS was observed. Ten years of ALPPS have
resulted in diverse publications with a high concern of bias. Although one
randomized study has been published, a more critical approach towards
retrospective methodology is needed to allow pragmatic conclusions for HPB
surgeons.
PMID- 29954640
TI - Moderate coffee intake and cardiovascular health; no grounds for concern.
PMID- 29954641
TI - Vitamin D replacement ameliorates serum lipoprotein functions, adipokine profile
and subclinical atherosclerosis in pre-menopausal women.
AB - BACKGROUND AND AIMS: Low vitamin D (vitD) has been linked to increased
cardiovascular (CV) risk, but the effects of vitD supplementation are not
clarified. We evaluated the impact of vitD normalization on HDL cholesterol
efflux capacity (CEC), which inversely correlates with CV risk, the
proatherogenic serum cholesterol loading capacity (CLC), adipokine profile and
subclinical atherosclerosis. METHODS AND RESULTS: Healthy premenopausal women
with vitD deficiency (n = 31) underwent supplementation. Subclinical
atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave
velocity (PWV) and augmentation index (AIx), measured with standard techniques.
HDL CEC and serum CLC were measured by a radioisotopic and fluorimetric assay,
respectively. Malondialdehyde (MDA) in HDL was quantified by the TBARS assay. Pre
beta HDL was assessed by 2D-electrophoresis. Serum adipokines were measured by
ELISA. VitD replacement restored normal levels of serum 25-hydroxyvitamin D
(25OHD) and significantly improved FMD (+4%; p < 0.001), PWV (-4.1%: p < 0.001)
and AIx (-16.1%; p < 0.001). Total CEC was significantly improved (+19.5%; p =
0.003), with a specific increase in the ABCA1-mediated CEC (+70.8%; p < 0.001).
HDL-MDA slightly but significantly decreased (-9.6%; p = 0.027), while no
difference was detected in pre-beta HDL. No change was observed in aqueous
diffusion nor in the ABCG1-mediated CEC. Serum CLC was significantly reduced (
13.3%; p = 0.026). Levels of adiponectin were increased (+50.6%; p < 0.0001) and
resistin levels were decreased (-24.3%; p < 0.0001). After vitD replacement, an
inverse relationship was found linking the ABCA1-mediated CEC with pre-beta HDL
(r2 = 0.346; p < 0.001) and resistin (r2 = 0.220; p = 0.009). CONCLUSION: Our
data support vitD supplementation for CV risk prevention.
PMID- 29954642
TI - Neuroplastic change of cytoskeleton in inferior colliculus after auditory
deafferentation.
AB - Neural plasticity is a characteristic of the brain that helps it adapt to changes
in sensory input. We hypothesize that auditory deafferentation may induce plastic
changes in the cytoskeleton of the neurons in the inferior colliculus (IC). In
this study, we evaluated the dynamic status of neurofilament (NF) phosphorylation
in the IC after hearing loss. We induced auditory deafferentation via unilateral
or bilateral cochlear ablation in rats, aged 4 weeks. To evaluate cytoskeletal
changes in neurons, we evaluated mRNA fold changes in NF heavy chain expression,
non-phosphorylated NF protein fold changes using SMI-32 antibody, and the ratio
of SMI-32 immunoreactive (SMI-32-ir) neurons to the total neuronal population in
the IC at 4 and 12 weeks after deafness. In the bilateral deafness (BD) group,
the ratios of SMI-32-ir neurons significantly increased at 4 weeks after ablation
in the right and left IC (6.1 +/- 4.4%, 5.0 +/- 3.4%, respectively), compared
with age-matched controls (P < 0.01, P < 0.01). At 12 weeks after ablation, the
ratio of SMI-32 positive neurons was higher (right, 3.4 +/- 2.0%; left, 3.2 +/-
2.3%) than that in the age-matched control group, albeit not significant in the
right and left side (P = 0.38, P = 0.24, respectively). Consistent with the
results of the ratio of SMI-32-ir neurons, SMI-32-ir protein expression was
increased at 4 weeks after BD, and the changes at 12 weeks after bilateral
ablation were not significant in the right or left IC. The age-matched control
fold changes of NF mRNA expression after bilateral deafness were not significant
at 4 and 12 weeks after deafness in right and left IC. Unilateral deafness did
not induce significant change of NF mRNA expression, SMI-32-ir protein
expression, and the ratio of SMI-32-ir neurons in the IC at 4 and 12 weeks after
hearing loss. Bilateral auditory deafferentation induces structural changes in
the neuronal cytoskeleton within the IC, which is prominent at 4 weeks after BD.
The structural remodeling of neurons stabilized at 12 weeks after BD. Unlike BD,
unilateral auditory deafferentation did not affect the dynamic status of NFs in
the IC.
PMID- 29954643
TI - Alterations of mandibular movement patterns after total joint replacement: a case
series of long-term outcomes in patients with total alloplastic temporomandibular
joint reconstructions.
AB - According to recognized guidelines, a total alloplastic replacement may be
indicated to resolve temporomandibular pain and functional limitations in cases
where conservative and less aggressive surgical management strategies have
failed. It is broadly believed that, as a result of the surgical procedure, the
function of the lateral pterygoid muscle is lost and so are the laterotrusive and
protrusive jaw movements. Furthermore, the joint prosthesis design may not be
conducive to lateral and protrusive movements. Using a dynamic stereometry
technique, it was possible to perform a quantitative analysis of kinematics in
TJR patients. The cases of four patients who showed preserved lateral and/or
protrusive motion are presented here. During mouth opening, prosthetic condyle
translation ranged from 3.18mm to 10.09mm and it was also possible to observe
this clinically. It has been suggested that changes in prosthesis design may have
improved postoperative jaw kinematics. Considering the large diversity in
treatment outcomes, it is recommended that the individual prognosis should always
be discussed with the patient prior to surgery.
PMID- 29954644
TI - Pseudotumor cerebri syndrome (PCTS) - Losing sight in patients and doctors with
regards to a growing epidemic.
PMID- 29954645
TI - Community-Engaged Lifestyle Medicine: Building Health Equity Through Preventive
Medicine Residency Training.
AB - Vulnerable populations in the U.S. experience persistent disparities in chronic
disease and associated lifestyle-based risk factors. Because of environmental,
cultural, and health systems barriers affecting vulnerable populations, lifestyle
medicine interventions may miss those at highest risk for chronic disease.
Numerous reports suggest that graduate medical education (GME) inadequately
prepares physicians to promote healthy lifestyles and health equity in vulnerable
groups. General Preventive Medicine/Public Health (GPM/PH), the medical specialty
dedicated to health promotion and disease prevention in populations, can fill
this gap. However, virtually no published reports describe health equity-oriented
GPM/PH residency programs. The authors describe implementation of the novel
Community-Engaged Lifestyle Medicine at the University of Texas Rio Grande Valley
GPM/PH residency program between 2017 and 2018. Community-Engaged Lifestyle
Medicine applies community engagement principles to lifestyle medicine practice,
training residents in multilevel, intersectoral approaches promoting behavior
change and health equity. Community-Engaged Lifestyle Medicine is described in
the context of health equity and the local border community, along with
associated curricular objectives and experiences. In 2017, the authors assessed
first-year Community-Engaged Lifestyle Medicine process outcomes, fidelity to
health equity mechanisms, and feasibility in a GPM/PH residency, by mapping
Community-Engaged Lifestyle Medicine activities to American Council of Graduate
Medical Education and the American College of Lifestyle Medicine competencies.
The Community-Engaged Lifestyle Medicine framework was successfully implemented
in 2017, meets all American Council of Graduate Medical Education competency
domains, and demonstrates fidelity to mechanisms of community engagement, health
equity, and the practice of lifestyle medicine. Community-Engaged Lifestyle
Medicine represents a feasible and valid framework to promote health equity via
GPM/PH and GME training and practice.
PMID- 29954646
TI - Recycling of ferromanganese gas cleaning plant (GCP) sludge by novel
agglomeration.
AB - Ferroalloy industries rely on minerals which are not available in pure form. The
total value chain is very cost intensive and market driven. From mineral and
environment conservation point of view every possible aspect must be explored for
the economic utilisation of waste and low-grade ores. Unlike other metallurgical
processes, Ferro alloys production generates a wide variety of waste rich in
manganese/chrome which has a potential for recycling back. Fine size, high
moisture content and presence of alkalis categorise this material into hazardous
waste and economically non-viable. The challenge is to convert such anthropogenic
material into a suitable feedstock for the furnace. In this article, the results
of smelting trials carried out in electric arc furnace (EAF) using novel extruded
briquettes (BREX) produced from the wastes of ferroalloy plant is discussed. The
briquette produced by this technique exhibit high physical and metallurgical
property and can replace the natural ore as a charge to some extent. Extruded
briquettes (BREX) can be efficiently used as one of the essential charge
component (up to 30% of the ore part of the charge) for the Silicomanganese
smelting thus improving technical and economical parameters of the furnace and
decreasing the self-cost of the Silicomanganese production.
PMID- 29954647
TI - Quantitative analysis of the safety and efficacy of microvascular decompression
for patients with trigeminal neuralgia above and below 65 years of age.
AB - For medically-refractory trigeminal neuralgia (TN), microvascular decompression
(MVD) is the first-line treatment, and has demonstrated the greatest efficacy and
durability. However, due to potential surgical complications, a bias may exist
against performing MVD in elderly patients. We sought to determine through a
quantitative analysis whether MVD in the elderly is a safe and effective
procedure for TN. We completed a Pubmed/SCOPUS literature search up to 12/2016
for eligible studies on MVD for TN. Only research articles with age
stratification of results were included. In this quantitative analysis, we
analyzed the data for the six articles identified in the literature comparing MVD
for a group of patients >=65 years with an elderly group <65 years. A total of
1483 were included. 455 patients were >=65 years (mean 70.8 years, range 65-89
years) and 1028 patients were <65 years (mean 53.4 years, range 19-64 years).
Composite mean follow-up time was 51.6 months for the elderly group, and 55.1
months for the young group. Following MVD, each group had 1 mortality (p = 0.43).
There were 21 serious morbidities in the elderly group (4.62%) and 32 in the
young group (3.11%) (p = 0.11). In addition, 15 patients (1.46%) in the elderly
group and 24 patients (1.62%) in the young group experienced a cerebrospinal
fluid leak (p = 0.23). TN recurrence rates 9.23% in the young group and 13.33% in
the elderly group (p = 0.070). In conclusion, for properly-selected surgical
candidates, MVD should not be ruled out on the basis of age >=65 years.
PMID- 29954648
TI - Parenting Intervention to Improve Nutrition and Physical Activity for
Preschoolers with Type 1 Diabetes: A Feasibility Study.
AB - OBJECTIVE: This study reports the feasibility and acceptability of a healthy
eating and physical-activity-focused behavioral intervention for parents of young
children with type 1 diabetes (T1D). METHODS: Ten parents of young children (age
2-5 years) with T1D enrolled. The intervention included six behavioral sessions
(five by telephone), diabetes nursing consultation, parent coach contact, text
messages, and a study website. Analyses explored feasibility, acceptability, and
preliminary findings. RESULTS: There was evidence of high acceptability (mean
parent satisfaction = 1.11, very satisfied). Although most participants completed
all of the assessments, there were some barriers to data collection devices. The
number of participants within the American Diabetes Association recommended
glycemic range doubled; there was no significant change in hemoglobin A1c, diet,
or physical activity. CONCLUSION: There was evidence of feasibility and
acceptability and initial evidence of change in hypothesized directions. Minor
changes were made for the larger randomized controlled trial.
PMID- 29954649
TI - Association between intrapartum epidural use and maternal postpartum depression
presenting for medical care: a population-based, matched cohort study.
AB - PURPOSE: To evaluate whether intrapartum epidural use is associated with maternal
postpartum depression presenting for medical care. METHODS: Population-based,
matched cohort study including all adult nulliparous women in Ontario, Canada
from 2006 to 2012 without a history of depression, who had a term vaginal
delivery. Seventy covariates including maternal demographics, medical and
psychiatric conditions, prenatal and perinatal complications, and healthcare
utilization were measured. Primary exposure was intrapartum epidural use. Primary
outcome was the onset of depression requiring medical care within 12 months
postpartum; and the secondary outcome was self-harm. RESULTS: A total of 40303
women who received an intrapartum epidural were matched 1:1 on age, year of
cohort entry, and propensity score to an equal number of women who did not
receive an intrapartum epidural. Overall rate of new onset depression presenting
to the healthcare system was 0.88% within 12 months postpartum. Intrapartum
epidural use was not associated with maternal postpartum physician or hospital
visits (adjusted HR 1.05 [95% CI 0.87 to 1.28]) or self-harm (unadjusted HR 0.91
[95% CI 0.57 to 1.48]). CONCLUSIONS: Intrapartum epidural use was not associated
with maternal postpartum depression presenting to the healthcare system in term
nulliparous women who had a vaginal delivery. Further research is needed to
determine if intrapartum epidural use is associated with postpartum depression
among women who don't seek care from a physician.
PMID- 29954650
TI - A review of blood pressure measurement in obese pregnant women.
AB - Blood pressure monitoring is a critical component of antenatal, peripartum and
postnatal care. The accurate detection and treatment of abnormal blood pressure
during pregnancy is essential for the optimisation of maternal and neonatal
outcomes. Increasing maternal obesity in western populations is well documented.
The presence of a large arm circumference in obese pregnant women may lead to
difficult and inaccurate blood pressure measurements. Difficulties measuring
blood pressure in non-pregnant obese patients are well described. In the
literature, the problem is uncommonly mentioned in relation to pregnant patients.
This topic review will discuss the importance and challenges of blood pressure
measurement in pregnancy. The currently available equipment for blood pressure
monitoring in pregnancy will be identified and the process of validating devices
described. The limitations of the current validation protocols in pregnancy will
be highlighted. It is concluded that a pregnancy-specific validation protocol is
required: this would facilitate the introduction of new technology for use in
high-risk pregnant women. More accurate blood pressure measurement has the
potential to improve the diagnosis and management of abnormal blood pressure in
pregnancy and influence maternal and neonatal outcomes.
PMID- 29954651
TI - Bottlenose dolphin (Tursiops truncatus) sperm revisited: Motility, morphology and
ultrastructure of fresh sperm of consecutive ejaculates.
AB - Computer aided sperm analysis systems allow detailed examination of sperm
motility and morphology variables, which are important for the understanding of
the spermatology of a species and the development of assisted reproductive
techniques. Cetacean biology is too complex to study in the wild and data from
captive individuals provide an important alternative for the conservation of
these charismatic animals. The present study evaluates ejaculate and sperm
characteristics, including sperm motility, kinematic variables and quantitative
sperm morphology and ultrastructure, of consecutive ejaculates from Atlantic
bottlenose dolphins (Tursiops truncatus). Sperm concentrations and total and
progressive motilities were greater in the second than the first ejaculate, with
all ejaculates being of very high quality (6.9-1127 * 106/ml sperm concentration,
75% to 91% total motility and 89% to 96% normal sperm). Most sperm in an
ejaculate (>=84%) were highly (VCL>150 MUm/s) and progressively motile with very
few abnormal sperm. The sperm have small heads, a short but very bulky midpiece
and a long tail. Detailed sperm morphometrics using CASA indicated there were
similarities from one ejaculate to the next. The large mitochondria with
extensive cristae mitochondriales are tightly packed in the midpiece resulting in
a large midpiece volume. All the semen and sperm characteristics indicate high
quality sperm and support the assumption that a multimale mating system is
present in T. truncatus.
PMID- 29954652
TI - Assessment of hair metal levels in aluminium plant workers using scalp hair ICP
DRC-MS analysis.
AB - The objective of the present study was to assess the level of aluminium and toxic
metals in hair of workers occupationally exposed to aluminium. 124 employees of
the aluminium plant working in the hydrometallurgical (n = 43) and sintering
units (n = 41), as well as 40 occupationally nonexposed controls were examined.
Hair aluminium (Al), arsenic (As), beryllium (Be), cadmium (Cd), mercury (Hg),
nickel (Ni), lead (Pb), and tin (Sn) content was assessed using inductively
coupled plasma mass spectrometry. The obtained data demonstrate that aluminium
plant workers had significantly higher levels of hair Al (28.8 (15.4-58.6) vs 7.8
(4.3-14.2) MUg/g, p < 0.001), Cd (0.053 (0.032 - 0.095) vs 0.025 (0.014 - 0.043)
MUg/g, p < 0.001) and Pb (0.672 (0.299-1.310) vs 0.322 (0.170 - 0.609) MUg/g, p =
0.012) than the controls, respectively. Further analysis demonstrated that
persons involved in different technological processes were characterized by
distinct hair metal profiles. Hair Al, Be, Cd, Ni, Pb, and Sn levels in men
working in the sintering unit of the aluminium plant exceeded the respective
control values. In turn, workers of the hydrometallurgical unit were
characterized by more than 2-fold higher levels of Al and Cd in hair as compared
to the controls. The results of the present study demonstrate that workers of the
aluminium plant are characterized by increased risk of Al as well as As, Cd, Pb,
and Sn exposure.
PMID- 29954654
TI - Using cognitive interviewing to improve questionnaires: An exemplar study
focusing on individual and condition-specific factors.
AB - Questionnaires are a standard component of quantitative research, but seldom do
researchers consider the importance of item clarity and participant
comprehension. This is particularly true among the often overlooked individual
and condition-specific items which characterize the patient and disease process.
Cognitive interviewing is one approach to assess item clarity and identify how
participants understand and respond to questions. The purpose of this paper is to
describe the process of cognitive interviewing used to identify questions that
are unclear or challenging to answer for a unique population, emerging adults
(age 18-29) with inflammatory bowel disease (IBD). Through cognitive interviewing
four areas were identified as needing improvement among individual and condition
specific items: 1) clarity - describing terms and adding details to item
directions; 2) cognitive recall burden - rewording questions to avoid the need
for mental math, 3) timeframe - adding phrases like 'in the past 2 weeks,' and 4)
question relevance - including items on disease remission. Analysis of these four
areas may guide other researchers working with IBD patients to obtain high
quality data, as well as stimulate questionnaire adaption using cognitive
interviewing with other populations. Cognitive interviewing can be useful when
drafting a new questionnaire or when adapting an established questionnaire; in
either case, it can enhance item clarity and participant comprehension.
PMID- 29954657
TI - ABIM Maintenance of Certification: Options for ACC Members.
PMID- 29954653
TI - Evolution of Salmonella within Hosts.
AB - Within-host evolution has resulted in thousands of variants of Salmonella that
exhibit remarkable diversity in host range and disease outcome, from broad host
range to exquisite host restriction, causing gastroenteritis to disseminated
disease such as typhoid fever. Within-host evolution is a continuing process
driven by genomic variation that occurs during each infection, potentiating
adaptation to a new niche resulting from changes in animal husbandry, the use of
antimicrobials, and emergence of immune compromised populations. We discuss key
advances in our understanding of the evolution of Salmonella within the host,
inferred from (i) the process of host adaptation of Salmonella pathovars in the
past, and (ii) direct observation of the generation of variation and selection of
beneficial traits during single infections.
PMID- 29954658
TI - Cardiovascular Therapies Targeting Left Atrial Appendage.
AB - Left atrial appendage (LAA) closure has evolved as an effective strategy for
stroke prevention in patients with atrial fibrillation who are considered
suitable for oral anticoagulation. There is strong evidence based on randomized
clinical trials with 1 percutaneous device, as well as a large registry
experience with several devices, regarding the safety and efficacy of this
strategy. In addition, there is encouraging data regarding the effect of
epicardial LAA closure on decreasing arrhythmia burden and improvements in
systemic homeostasis by neurohormonal modulation. However, there are several
unresolved issues regarding optimal patient selection, device selection,
management of periprocedural complications including device-related thrombus,
residual leaks, and pericarditis. In this review, we summarize the rationale,
evidence, optimal patient selection, and common challenges encountered with
mechanical LAA exclusion.
PMID- 29954659
TI - Representation of Women in American College of Cardiology/American Heart
Association Guideline Writing Committees.
PMID- 29954660
TI - The Untapped Pharmacopeic Potential of Helminths.
AB - The dramatic rise in immunological disorders that occurs with socioeconomic
development is associated with alterations in microbial colonization and reduced
exposure to helminths. Excretory-secretory (E/S) helminth products contain a
mixture of proteins and low-molecular-weight molecules representing the primary
interface between parasite and host. Research has shown great pharmacopeic
potential for helminth-derived products in animal disease models and even in
clinical trials. Although in its infancy, the translation of worm-derived
products into therapeutics is highly promising. Here, we focus on important key
aspects in the development of immunomodulatory drugs, also highlighting novel
approaches that hold great promise for future development of innovative research
strategies.
PMID- 29954661
TI - Rotator cuff contact pressures at the tendon-implant interface after anatomic
total shoulder arthroplasty using a metal-backed glenoid component.
AB - BACKGROUND: Rotator cuff tears following anatomic total shoulder arthroplasty
increase with duration of follow-up. This study aimed to evaluate contact
pressure between the rotator cuff tendons and prosthesis after anatomic total
shoulder arthroplasty and compare these with the tendon-contact pressures in the
native shoulder. METHODS: Eight entire upper extremities were mounted onto a
testing apparatus, and simulated muscle loading was applied to each rotator cuff
tendon with the shoulder positioned in abduction, internal rotation, and external
rotation. Pressure-sensitive film placed between each tendon and bone was used to
measure the resultant tendon contact pressures. Experiments were repeated after
anatomic total shoulder arthroplasty using standardized implant sizes, and
pressure-sensitive film was used to evaluate tendon-prosthesis contact pressure.
RESULTS: Both joint angle and shoulder joint replacement surgery had significant
effects on the maximum contact pressure measured between the humeral head and all
rotator cuff tendons (P < .05) except the teres minor. The supraspinatus
demonstrated a significantly larger peak tendon contact pressure after surgery at
45 degrees of abduction relative to that in the native shoulder (mean
difference, 0.2 MPa; P = .031), while the subscapularis had a significantly
larger maximum contact pressure at 10 degrees of abduction (mean difference,
0.45 MPa; P = .032) and 90 degrees of abduction (mean difference, 0.80 MPa; P =
.008) postoperatively. CONCLUSION: Anatomic total shoulder arthroplasty results
in significantly larger tendon contact pressures relative to those in the native
shoulder. High tendon contact pressures may ultimately predispose rotator cuff
tendons to postoperative wear-induced damage and tearing.
PMID- 29954662
TI - Environmental and Ecological Effects of Climate Change on Venomous Marine and
Amphibious Species in the Wilderness.
AB - INTRODUCTION: Recent analyses of data show a warming trend in global average air
and sea surface ocean temperatures. The atmosphere and ocean have warmed, the
amounts of snow and ice have diminished, the sea level has risen, and the
concentrations of greenhouse gases have increased. This article will focus on
climate change and projected effects on venomous marine and amphibious creatures
with the potential impact on human health. METHODS: Retrospective analysis of
environmental, ecological, and medical literature with a focus on climate change,
toxinology, and future modeling specific to venomous aquatic and amphibious
creatures. Species included venomous jellyfish, poisonous fish, crown-of-thorns
starfish, sea snakes, and toxic frogs. RESULTS: In several projected scenarios,
rising temperatures, weather extremes, and shifts in seasons will increase
poisonous population numbers, particularly with certain marine creatures like
jellyfish and crown-of-thorns starfish. Habitat expansions by lionfish and sea
snakes are projected to occur. These phenomena, along with increases in human
populations and coastal development will likely increase human-animal encounters.
Other species, particularly amphibious toxic frogs, are declining rapidly due to
their sensitivity to any temperature change or subtle alterations in the
stability of their environment. If temperatures continue to rise to record levels
over the next decades, it is predicted that the populations of these once
plentiful and critically important animals to the aquatic ecosystem will decline
and their geographic distributions will shrink. CONCLUSION: Review of the
literature investigating the effect and forecasts of climate change on venomous
marine and amphibious creatures has demonstrated that temperature extremes and
changes to climatic norms will likely have a dramatic effect on these
toxicological organisms. The effects of climate change on these species through
temperature alteration and rising coastal waters will influence each species
differently and in turn potentially affect commercial industries, travel,
tourism, and human health.
PMID- 29954663
TI - Noncanonical Hippo Signalling in the Regulation of Leukocyte Function.
AB - The mammalian sterile 20-like (MST) kinases are central constituents of the
evolutionary ancient canonical Hippo pathway regulating cell proliferation and
survival. However, perhaps surprisingly, MST1 deficiency in human patients leads
to a severe combined immunodeficiency syndrome with features of autoimmune
disease. In line with this, Mst1-deficient mice exhibit severe defects in
lymphocyte and neutrophil functions as well as disturbed intracellular vesicle
transport. These findings spurred research on the noncanonical functions of MST1
in leukocytes. Here, we summarise the latest findings on this topic and discuss
MST1 as a critical regulator of various leukocyte functions.
PMID- 29954664
TI - Robotic-assisted laparoscopic ureteral re-implant (RALUR): Can post-operative
urinary retention be predicted?
AB - OBJECTIVE: Urinary retention following robotic-assisted laparoscopic extravesical
ureteral reimplantation (RALUR) is proposed to be due to traction or injury of
the pelvic parasympathetic nerve plexus during distal ureteral dissection. Nerve
sparing techniques have been employed to avoid injury to the pelvic plexus,
either directly or indirectly. This single-center study assessed postoperative
urinary retention rates after extravesical RALUR and investigated whether
demographic or operative factors could predict this occurrence. METHODS: All
RALUR cases entered into an Institutional Review Board-approved registry were
retrospectively reviewed, and the rate of postoperative retention was determined.
Postoperative urinary retention was defined as the need for catheterization at
any time in the postoperative period during hospital admission or within 1 week
after the operation. This included acute urinary retention episodes (AUR) as well
as high post-void residuals (>50% of expected bladder capacity). Univariate
analysis was performed to analyze for predictors of postoperative retention.
Factors assessed included age, gender, clinical presentation, bowel bladder
dysfunction (BBD), pre-operative urinary tract infection (UTI), procedure length,
grade of vesicoureteral reflux (VUR), and operative laterality. RESULTS: A total
of 128 patients underwent extravesical RALUR in 179 ureters during the study
period 2012-2016. Male:female ratio was 1:2.6. Median age at surgery was 4 years.
Bilateral RALUR was performed in 52 cases (40.6%), and unilateral in 76 (59.4%).
Urinary retention requiring catheterization occurred in 11 cases (8.59%). Of
these, seven were post-bilateral RALUR, while the remaining four were unilateral.
In seven cases, postoperative retention occurred within 24 h following RALUR. The
remaining four instances occurred within 1 week, despite successful voiding in
the immediate postoperative period. Univariate analysis revealed male gender (P =
0.009) and operating room time (P = 0.029) as predictors of retention. No
association was found with age, weight, BBD, pre-operative UTI, grade of VUR, or
laterality. CONCLUSION: Urinary retention after RALUR was an infrequent
complication. When it did occur, urinary retention appeared to be secondary to
covariates such as male gender and length of surgical time - possibly an
indication of technical difficulty - rather than laterality of repair.
PMID- 29954665
TI - TGF-beta and mesenchymal stromal cells in regenerative medicine, autoimmunity and
cancer.
AB - Multipotent mesenchymal stromal cells (MSCs) represent a promising cell-based
therapy in regenerative medicine and for the treatment of inflammatory/autoimmune
diseases. Importantly, MSCs have emerged as an important contributor to the tumor
stroma with both pro- and anti-tumorigenic effects. However, the successful
translation of MSCs to the clinic and the prevention of their tumorigenic and
metastatic effect require a greater understanding of factors controlling their
proliferation, differentiation, migration and immunomodulation in vitro and in
vivo. The transforming growth factor(TGF)-beta1, 2 and 3 are involved in almost
every aspect of MSC function. The aim of this review is to highlight the roles
that TGF-beta play in the biology and therapeutic applications of MSCs. We will
discuss the how TGF-beta modulate MSC function as well as the paracrine effects
of MSC-derived TGF-beta on other cell types in the context of tissue
regeneration, immune responses and cancer. Finally, taking all these aspects into
consideration we discuss how modulation of TGF-beta signaling/production in MSCs
could be of clinical interest.
PMID- 29954666
TI - Gender differences in cardiovascular risk profiles and diabetes care among adults
with type 2 diabetes in Germany.
PMID- 29954667
TI - Efficacy and adverse effects of sotalol in adults with congenital heart disease.
AB - INTRODUCTION: Adults with congenital heart disease (CHD) are predisposed to
arrhythmias, which can often be refractory to medical therapy. Sotalol is an
attractive alternative antiarrhythmic to amiodarone in this younger patient
population, given the latter's toxicity profile, but it may have proarrhythmic
effects. We therefore aimed to assess the efficacy and safety of sotalol in
adults with CHD. METHODS: We retrospectively assessed our adult CHD database for
all patients >=16 years old, with moderate to highly complex defects, who were
prescribed sotalol between 2000 and 2017. Efficacy in treating the clinical
arrhythmia was assessed as complete, partial or failure. Adverse effects,
including proarrhythmia, were documented. RESULTS: Sotalol was prescribed in 82
of 902 adult CHD patients reviewed (9%). The mean age at sotalol commencement was
31.8 +/- 13.1 years, with a median time on sotalol of 2.8 years. The average
prescribed dose was 122 +/- 51 mg/daily. Sotalol was completely effective in 48%
(n = 39), partially effective in 46% (n = 38) and failed to control the clinical
arrhythmia in 6% (n = 5). Fifteen patients (18%) discontinued sotalol due to a
side effect, most commonly fatigue or dyspnoea. No episodes of torsades de
pointes or sudden cardiac death were observed. Significant bradycardia related to
sotalol occurred in 13% (n = 11, with permanent pacing implemented in 4), and was
associated with Fontan anatomy. CONCLUSIONS: In moderate to highly complex adult
CHD, sotalol was reasonably effective and safe in low doses. Side effects
limiting treatment were typically non-life-threatening, with significant
bradycardia related to sotalol more likely in Fontan patients.
PMID- 29954668
TI - Transseptal or retrograde approach for transcatheter ablation of left sided
accessory pathways: a systematic review and meta-analysis.
AB - BACKGROUND: Transcatheter ablation is the most effective treatment for patients
with symptomatic or high-risk accessory pathways (AP). At present, no clear
recommendations have been issued on the optimal approach for left sided AP
ablation. We performed this meta-analysis to compare the safety and efficacy of
transaortic retrograde versus transseptal approach for left sided AP ablation.
METHODS AND RESULTS: MEDLINE/PubMed and Cochrane database were searched for
pertinent articles from 1990 until 2016. Following inclusion/exclusion criteria
application, 29 studies were selected including 2030 patients (1013 retrograde,
1017 transseptal) from 28 observational single Centre studies and one randomized
trial. Patients approached by transseptal puncture presented a significantly
higher acute success (98% vs. 94%, p = 0.040). The incidence of late recurrences
(p = 0.381) and complications (p = 0.301) did not differ among the two groups,
but the pattern of complications differed: vascular complications were more
frequent with transaortic retrograde approach, while cardiac tamponade was the
main transseptal complication. No difference was noted in terms of procedural
duration and fluoroscopy time (p = 0.230 and p = 0.980, respectively). Meta
regression analysis showed no relation between year of publication and acute
success (p = 0.325) or incidence of complications (p = 0.795); additionally, no
direct relation was found between age and acute success (p = 0.256) or
complications (p = 0.863). CONCLUSIONS: Left sided AP transcatheter ablation is
effective in around 95% of the cases, with a very limited incidence of
complications. Transseptal access provides higher acute success in achieving AP
ablation; late recurrences are rare but observed similarly following both
approaches. Retrograde approach is affected by a relatively high incidence of
vascular complications.
PMID- 29954669
TI - Cardiac protection by moving the mitochondria?
PMID- 29954670
TI - ST2 and left ventricular remodeling after ST-segment elevation myocardial
infarction: A cardiac magnetic resonance study.
AB - BACKGROUND: The association of soluble interleukin-1 receptor-like 1 (ST2) with
left ventricular (LV) remodeling is unclear in patients with a first ST-segment
elevation myocardial infarction (STEMI). The objective of this work was to assess
the relationship between ST2, a marker of inflammation, and cardiac magnetic
resonance (CMR) imaging-derived LV remodeling after a first STEMI. METHODS: We
prospectively evaluated 109 patients with a first STEMI treated with primary
percutaneous coronary intervention who had ST2 assessed 24 h post-reperfusion.
All patients underwent CMR imaging 1 week and 6 months after STEMI. The
independent associations between ST2, LV diastolic and systolic volume indices,
and LV ejection fraction (LVEF) were evaluated by linear mixed models. RESULTS:
The mean age of the sample was 59 +/- 12 years, 85 patients (78%) were male, and
13 (11.9%) had a LVEF <=40%. The median (IQR) of ST2 was 55.3 (38.7-94.1) pg/mL.
At 1-week CMR higher ST2 was related to more infarct size and less myocardial
salvage index (p < 0.01). Overall, after comprehensive multivariable adjustment,
higher baseline ST2 was associated with progressive LV volume indices dilation
and LVEF deterioration (p < 0.05). This effect was stronger in patients with
severe 1-week structural damage, namely those with large infarct size, extensive
microvascular obstruction or LVEF <=40%. CONCLUSIONS: In patients with a first
STEMI treated with primary percutaneous coronary intervention, soluble ST2
predicts dynamic changes in CMR-derived LV volumes and LVEF. Future studies must
assess whether targeting interleukin-1 leads to lower ST2 levels and less LV
remodeling.
PMID- 29954671
TI - Coronary artery microvascular dysfunction: Role of sex and arterial load.
AB - BACKGROUND: The prognosis of cardiovascular disease is worse in women than men,
and coronary microvascular dysfunction explains the excess cardiovascular risk in
women. In addition, age-related increases in pulsatile arterial load are greater
in women than men; and lower arterial compliance has been shown to independently
predict cardiovascular events. However, whether arterial load differentially
affects the coronary microvasculature in men and women remains unknown. We
hypothesized that lower arterial compliance would be associated with coronary
artery microvascular dysfunction in women. METHODS AND RESULTS: 285 subjects (60%
women, age: 61.2 +/- 11.0 yrs) undergoing cardiac 82Rb positron-emission
tomography between 2010 and 2013, with ejection fraction >=50%, no heart failure,
dyspnea, coronary artery disease or regional perfusion defects were included.
Left ventricular microvascular function was assessed by myocardial flow reserve
(MFR). Pulsatile arterial load was estimated by indexed arterial compliance [ACi:
(stroke volume/pulse pressure)/BSA]. Multivariable linear regression evaluated
associations of arterial compliance with myocardial flow reserve after adjustment
for confounders. ACi was lower in women than men [0.39 +/- 0.15 vs. 0.52 +/- 0.28
(mL/mm Hg)/m2, P < 0.0001]. We found that the effect of ACi on MFR differs by
sex: lower ACi was associated with lower MFR in women (beta +/- SE: 0.20 +/-
0.07, P = 0.004) but not in men (0.03 +/- 0.11, P = 0.75). CONCLUSIONS: Lower ACi
was associated with altered coronary microvascular function in women, but not in
men. Our findings highlight low arterial compliance as a potential link between
hypertension, coronary microvascular dysfunction and adverse cardiovascular
events in women.
PMID- 29954672
TI - Authors' response to the letter re: Evidence based treatment for unstable slipped
upper femoral epiphysis: Systematic review and exploratory patient level
analysis.
PMID- 29954673
TI - Not just a matter of pain intensity: Effects of three different conditioning
stimuli on conditioned pain modulation effects.
AB - INTRODUCTION: Heterotopic conditioned pain modulation (CPM) has provided
potentially useful clinical information such as response to medication in
neuropathic pain or the prediction of pain after surgical procedures. Despite
these advances, several methodological aspects of CPM remain to be determined,
such as the impact of the conditioning stimulus (CS) type upon CPM, if its evoked
pain intensity is controlled for [measured on a visual analogue scale (VAS: 0
100mm)]. OBJECTIVES: To explore potential differential effects of CPM using three
distinct CS (having similar evoked-pain intensity) in the same individuals.
METHODS: We conducted a cross-over randomized study in healthy volunteers (HV)
and looked-for differences in the CPM effect evoked by three differing CS [cuff
pressure pain stimulation (CuPS), cold pressor test (CoPT), and thermode-based
cold painful stimulation (TCPS)] on the same test stimulus [(TS)-supra-threshold
heat pain stimulation with a contact-heat thermode). CPM was calculated as a
ratio: [conditioned TS VAS - unconditioned TS VAS]/[unconditioned TS VAS].
Importantly, the range of pain evoked by the unconditioned-TS and by the CS was
controlled for. Also, the unpleasantness evoked by the CS [visual analogue scale
(VAS: 0-100mm)] was measured before the initiation of the conditioned-TS.
RESULTS: Pain intensity VAS of the three unconditioned-TSs were similar between
the three sessions. CPM was significantly different between the three types of CS
(CoPT=-0.43+/-0.29; CuPS=-0.25+/-0.24; and TCPS=-0.23+/-0.35; P=.005): CoPT
induced significantly more robust CPM compared to CuPS (P=.004) and TCPS
(P=.005). CONCLUSIONS: Significantly different intensities of CPM can be evoked
on the same individual according to the nature of the CS, even when controlling
for the intensity of the unconditioned-TS, and the pain evoked by the CS. This
may have implications for the design of future recommendations and may impact the
translation of CPM from the laboratory to clinical practice.
PMID- 29954674
TI - Magnetic Resonance Imaging (MRI) Assessment of Residual Breast Cancer After
Neoadjuvant Chemotherapy: Relevance to Tumor Subtypes and MRI Interpretation
Threshold.
AB - PURPOSE: To investigate the diagnostic performance of magnetic resonance imaging
(MRI) for predicting pathologic complete response after neoadjuvant chemotherapy
(NAC) depending on subtypes of breast cancer using different interpretation
thresholds of MRI negativity. PATIENTS AND METHODS: A total of 353 women with
breast cancer who had undergone NAC were included. Pathologic examination after
complete surgical excision was the reference standard. Tumors were divided into 4
subtypes on the basis of expression of hormone receptor (HR) and human epidermal
growth factor receptor 2 (HER2). Tumor enhancement was assessed on early and late
phases of MRI. MRI negativity was divided into radiologic complete response (rCR,
complete absence of enhancement on both early and late phases) and near-rCR (no
discernible early enhancement but observed late enhancement). RESULTS: Ninety
(25.5%) of 353 patients experienced pathologic complete response. When analyzing
the data of all patients, sensitivity of MRI was higher for rCR versus near-rCR
(97.72% vs. 90.49%, P < .0001), whereas specificity was lower for rCR versus near
rCR (44.44% vs. 72.22%, P < .0001). Accuracy was equivalent (84.14% vs. 85.84%).
In HR-HER2+ tumors, 100% sensitivity and negative predictive value were achieved
by assessing early enhancement only. In HR+HER2- tumors, sensitivity of MRI was
higher for rCR versus near-rCR (96.12% vs. 86.82%, P = .0005). CONCLUSION:
Diagnostic performance of MRI after NAC differs in accordance with the subtypes
and threshold of MRI negativity. MRI assessment with consideration of tumor
subtypes is required, along with standardization of MRI interpretation criteria
in the NAC setting.
PMID- 29954675
TI - IL-17A - A regulator in acute inflammation: Insights from in vitro, in vivo and
in silico studies.
AB - Acute inflammation following sterile injury is both inevitable and necessary to
restore homeostasis and promote tissue repair. However, when excessive,
inflammation can jeopardize the viability of organs and cause detrimental
systemic effects. Identifying key-regulators of the immune cascade induced by
surgery is vital to attenuating excessive inflammation and its subsequent
effects. In this review, we describe the emerging role of IL-17A as a key
regulator in acute inflammation. The role of IL-17A in chronic disease states,
such as rheumatoid arthritis, psoriasis and cancer has been well documented, but
its significance in acute inflammation following surgery, sepsis, or traumatic
injury has not been well studied. We aim to highlight the role of IL-17A in acute
inflammation caused by trauma, liver ischemia, and organ transplantation, as well
as in post-operative surgical infections. Further investigation of the roles of
this cytokine in acute inflammation may stimulate novel therapies or diagnostic
modalities.
PMID- 29954676
TI - Ultrasonic/CT image fusion guidance facilitating percutaneous catheter drainage
in treatment of acute pancreatitis complicated with infected walled-off necrosis.
AB - BACKGROUND: As the firs-line treatment for acute pancreatitis (AP) related
infectious walled-off necrosis (WON), percutaneous catheter drainage (PCD) are
usually accomplished under CT or US guidance, either of which has certain
disadvantages. It is necessary to verify the clinical effects of using US and CT
images fusion as guidance of PCD. METHODS: The total 94 consecutive AP patients
with infected WON from January of 2013 to January of 2017 were included. Among
these patients with infected WON, 48 received PCD under simple US guidance (US
PCD) and 46 under US/CT images fusion guidance (US/CT-PCD). The clinical data
consisting of puncture data, drainage effectiveness indicators, intervention
complications were collected. RESULTS: The demographic characteristics and
disease related characteristics of two groups were comparable. After 48 h of PCD
treatment, the US/CT-PCD group achieved a significantly higher imaging effective
rate, and significantly lower inflammatory response indexes and severity score,
than the US-PCD group (P < 0.05). The US/CT-PCD group required fewer puncture
times and drainage tubes and lower rate of advanced treatment, showing higher
operational success rate than the US-PCD group (P < 0.05). Moreover, the US/CT
PCD group exhibited significantly fewer puncture related complications, lower
hospital stay, intubation time, and hospitalization expenses than the US-PCD
group (P < 0.05). CONCLUSION: PCD treatment under the US/CT images fusion
guidance is a reliable intervention with definite clinical effects for AP
complicated with infected WON.
PMID- 29954677
TI - Wilder Graves Penfield.
PMID- 29954678
TI - A new life after stroke.
PMID- 29954679
TI - Nurses' and physicians' knowledge and skills in non-invasive ventilation:
Equipment and contextual influences.
AB - OBJECTIVES: To assess non-invasive ventilation knowledge and skills among nurses
and physicians in different contexts: equipment and contextual influences.
METHOD: Cross-sectional, descriptive study in 4 intensive care units (ICU) (1
surgical, 3 medical-surgical), 1 postsurgical recovery unit, 2 emergency
departments (ED) and 3 wards, in 4 hospitals (3 university, 1 community) with 407
professionals. A 13-item survey, validated in the setting, was applied (Kappa
index, 0.97 (95% CI [.965-.975]). RESULTS: Nurses (63.7% response); physicians
(39% response). The overall percentage of correct responses was 50%. Scored from
1 to 5, with lower scores reflecting more knowledge, nurses scored 3.27+/-.5 vs
2.62+/-.5 physicians, respectively (mean difference,.65 (95% CI: .48-.82,
P<.001). There were no differences between hospitals or units (P=.07 and P=.09).
A notable percentage of respondents incorrectly identified the patient-ventilator
synchronization strategy as "covering the expiratory port" (intentional leaks)
and pressing the mask against the patient's face (unintentional leaks) (28.2%
ICU, 22.5% ED, 8.3% postoperative resuscitation, 61.5% wards), with no difference
between nurses and physicians (27.9% vs 23.4%, P=.6). Only 50% of nurse
respondents correctly answered a question about measuring mask size and just
11.7% of the nurses knew the "2-finger fit" adjustment. CONCLUSIONS: There was no
difference in nurses' and physicians' knowledge according to the setting studied.
The lack of knowledge regarding NIV therapy depended on training received and
material available. To reduce the existent confusion between intentional and
nonintentional leak, the use of a single type of NIV supply and providing an
appropriate level of training for nurses is recommended.
PMID- 29954680
TI - Comparing Outcomes of Patients With Early-Stage Non-Small-Cell Lung Cancer
Treated With Stereotactic Body Radiotherapy Based on Frailty Status.
AB - INTRODUCTION: Frailty of surgical patients has been associated with worse
outcomes. There is limited literature discussing frailty in patients with lung
cancer treated with stereotactic body radiotherapy (SBRT). This study assesses
the relationship between frailty and overall survival (OS), tumor control, and
toxicity in patients with early-stage non-small-cell lung cancer (NSCLC) treated
with SBRT. PATIENTS AND METHODS: A retrospective review of patients with early
stage NSCLC treated with SBRT at a single institution between February 2009 and
September 2014 was performed. A modified frailty index (mFI) of 8 variables was
created, and patients were categorized as nonfrail (mFI <= 2) and frail (mFI >
2). OS, recurrence-free survival (RFS), local control (LC), regional control, and
distant control (DC) were compared between frail and nonfrail patients by Kaplan
Meier analysis and log-rank tests. Univariate and multivariable analyses were
conducted. RESULTS: One hundred forty cases of early-stage NSCLC were included,
with 49 frail (35.0%) and 91 nonfrail (65.0%) subjects. OS was significantly
lower in frail than nonfrail patients (P = .01) with 3-year OS of 59.3% versus
82.0%. LC and DC were significantly lower in frail than nonfrail patients (LC: P
= .02, 3-year LC of 85.3% vs. 97.0%; DC: P = .03, 3-year DC of 80.6% vs. 93.4%),
as was RFS (P = .01, 3-year RFS of 53.4% vs. 74.5%). Frailty remained a
significant predictor for shorter OS on multivariable analysis (hazard ratio =
1.98; 95% confidence interval, 1.02-3.85; P = .04). CONCLUSION: Frailty is
associated with reduced OS in early-stage NSCLC patients treated with SBRT.
Characterizing frailty using an mFI before treatment could help guide treatment
decision making and patient counseling.
PMID- 29954681
TI - Synthesis and pharmacological evaluation of pyrazolo[4,3-c]quinolinones as high
affinity GABAA-R ligands and potential anxiolytics.
AB - The synthesis, in vitro ligand binding study and in vivo Elevated Plus Maze test
(EPM) of a series of pyrazolo[4,3-c]quinolin-3-ones (PQs) are reported. Multistep
synthesis of PQs started from anilines and diethyl 2-(ethoxymethylene)malonate to
give the quinolin-4-one nucleus, via the Gould-Jacobs reaction. These
quinolinones were transformed to 4-chloroquinolines, which react with aryl
hydrazines affording the final compounds. PQs exhibited different potency in
displacing specific [3H]Flunitrazepam binding from the benzodiazepine binding
site at the gamma-aminobutyric acid receptor (GABAA-R) depending on the
substitution of the pyrazoloquinolone nucleus. PCA helped determine how different
substituents contributed to the differential behavior of the PQs studied.
Compounds with high affinity for the GABAA-R were tested regarding their
anxiolytic properties in Wistar adult male rats using the Elevated Plus Maze
(EPM). Thus, PQs with a p-methoxy phenyl group at N-1 (7b-ii and 7c-ii) displayed
a remarkable anxiolytic activity at low doses (0.5-1.0 mg/kg). Meanwhile, PQs
featuring an unsubstituted phenyl (7b-i) or p-fluoro phenyl group (7b-iii) at the
N-1 showed anxiogenic effects in the EPM test.
PMID- 29954682
TI - Design, synthesis and biological evaluation of nitric oxide releasing derivatives
of dapagliflozin as potential anti-diabetic and anti-thrombotic agents.
AB - The cardiovascular complications were highly prevalent in type 2 diabetes
mellitus (T2DM), even at the early stage of T2DM or the state of intensive
glycemic control. Therefore, there is an urgent need for the intervention of
cardiovascular complications in T2DM. Herein, the new hybrids of NO donor and
SGLT2 inhibitor were design to achieve dual effects of anti-hyperglycemic and
anti-thrombosis. As expected, the preferred hybrid 2 exhibited moderate SGLT2
inhibitory effects and anti-platelet aggregation activities, and its anti
platelet effect mediated by NO was also confirmed in the presence of NO
scavenger. Moreover, compound 2 revealed significantly hypoglycemic effects and
excretion of urinary glucose during an oral glucose tolerance test in mice.
Potent and multifunctional hybrid, such as compound 2, is expected as a potential
candidate for the intervention of cardiovascular complications in T2DM.
PMID- 29954683
TI - Design, synthesis and anticancer evaluation of acridine hydroxamic acid
derivatives as dual Topo and HDAC inhibitors.
AB - Multitarget inhibitors design has generated great interest in cancer treatment.
Based on the synergistic effects of topoisomerase and histone deacetylase
inhibitors, we designed and synthesized a new series of acridine hydroxamic acid
derivatives as potential novel dual Topo and HDAC inhibitors. MTT assays
indicated that all the hybrid compounds displayed good antiproliferative
activities with IC50 values in low micromolar range, among which compound 8c
displayed potent activity against U937 (IC50 = 0.90 MUM). In addition, compound
8c also displayed the best HDAC inhibitory activity, which was several times more
potent than HDAC inhibitor SAHA. Subsequent studies indicated that all the
compounds displayed Topo II inhibition activity at 50 MUM. Moreover, compound 8c
could interact with DNA and induce U937 apoptosis. This study provides a suite of
compounds for further exploration of dual Topo and HDAC inhibitors, and compound
8c can be a new dual Topo and HDAC inhibitory anticancer agent.
PMID- 29954684
TI - DXA-Derived Lean Mass Includes the Fat-Free Component of Adipose Tissue: Impact
on Training-Induced Changes in Body Composition.
PMID- 29954685
TI - Outcome Predictors in Congenital Cardiac Care: No More a Hunch or a Curiosity but
an Ethical and Financial Necessity.
PMID- 29954687
TI - Differences in meconium stained amniotic fluid in an Australian population: A
retrospective study.
AB - BACKGROUND: Meconium stained amniotic fluid commonly occurs postdates ( >40 weeks
gestation) indicating fetal maturity. Previous literature indicates that
different ethnicities mature at different rates. AIM: To compare the rate of
meconium stained amniotic fluid of Australian-born and non-Australian born women.
METHODS: A retrospective correlation study design was implemented, using data
collected in the birth outcomes system at one tertiary hospital. Data was
collected from all women who gave birth to a term (>/=37 weeks gestation),
singleton, liveborn baby between January 1st to December 31st, 2014. Maternal
country of birth was used for comparison. Categorical data was analyzed using Chi
Square test for Independence. Continuous variables were assessed for normality,
and differences were compared using an Independent t-test or a Mann-Whitney U
test. All tests were two-tailed and p<0.05 was considered statistically
significant. RESULTS: 3,041 women were included; 1131 Australian-born and 1910
non-Australian born. Meconium stained amniotic fluid occurred more frequently in
non-Australian born women compared to Australian-born women (23.5% vs. 19.8
p=0.02). Their babies were significantly smaller (Mean=3265g, Standard Deviation
463.8 vs Mean=3442g, Standard Deviation 499.2, p<0.001), with no difference in
gestational length (Mean=39.4, Standard Deviation 1.28 vs Mean=39.5, Standard
Deviation 1.18, p=0.06). Increasing gestational age had the strongest association
with meconium stained amniotic fluid; >/=42 weeks gestation occurring 3.52 (95%
Confidence Interval: 2.00, 6.22, p=<0.001) more than <40 weeks gestation.
CONCLUSION: Maternity health services should record ethnicity and region of birth
to provide individualised care as women born overseas often have poorer perinatal
outcomes when compared to Australian-born women.
PMID- 29954686
TI - Elevated serum vascular endothelial growth factor and development of cardiac
allograft vasculopathy in children.
AB - BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of
retransplantation and death in pediatric heart transplant recipients. Our aim was
to evaluate the association between serum vascular endothelial growth factor-A
(VEGF) and CAV development in the pediatric heart transplant population. METHODS:
In this retrospective study performed at a university hospital, VEGF
concentrations were measured by enzyme-linked immunosorbent assay in banked serum
from pediatric heart transplant recipients undergoing routine cardiac
catheterization. In subjects with CAV (n = 29), samples were obtained at 2 time
points: before CAV diagnosis (pre-CAV) and at the time of initial CAV diagnosis
(CAV). In subjects without CAV (no-CAV, n = 16), only 1 time-point was used. VEGF
concentrations (n = 74) were assayed in duplicate. RESULTS: Serum VEGF is
elevated in pediatric heart transplant recipients before catheter-based diagnosis
of CAV (no-CAV mean: 144.0 +/- 89.05 pg/ml; pre-CAV mean: 316.2 +/- 118.3 pg/ml;
p = 0.0002). Receiver-operating characteristic curve analysis of pre-CAV VEGF
levels demonstrated an area under the curve of 87.7% (p = 0.0002), with a VEGF
level of 226.3 pg/ml predicting CAV development with 77.8% sensitivity and 91.7%
specificity. VEGF is similarly elevated in subjects with angiographically
diagnosed CAV and in those with normal angiography but intravascular ultrasound
(IVUS) evidence of CAV. CONCLUSIONS: The increase in serum VEGF before onset of
detectable CAV is fundamental to its utility as a predictive biomarker and
suggests further investigations of VEGF in the pathogenesis of CAV are warranted
in the pediatric heart transplant population.
PMID- 29954688
TI - Childbirth education in Australia: Have we lost our way?
PMID- 29954689
TI - Attitudes and perceptions of pregnant women towards the use of Anti-Retroviral
Therapy in Nigeria.
AB - BACKGROUND: Mother-to-child transmission of Human Immunodeficiency Virus
continues to be a major problem in Nigeria. Despite several initiatives, the
number of infected pregnant women receiving Anti-Retroviral Therapy to prevent
mother-to-child transmission of the virus remains low in Nigeria. Evidence
suggests that attitudes and perceptions of the pregnant women influence their use
of Anti-Retroviral Therapy. AIM: To understand the attitudes and perceptions of
Human Immunodeficiency Virus infected pregnant women towards the use of Anti
Retroviral Therapy for prevention of mother-to-child transmission in Nigeria.
METHOD: Twenty four Human Immunodeficiency Virus infected pregnant women were
purposively selected from antenatal clinics. Women's attitudes and perceptions
towards the use of Anti-Retroviral Therapy were explored using semi-structured in
depth interviews conducted in May/June 2016. All interviews were recorded,
transcribed and analysed using thematic approach. FINDINGS: Overall, participants
reflected a positive attitude about using Anti-Retroviral Therapy to prevent
mother-to-child transmission and perceived the treatment as beneficial. The main
themes identified included: perceived benefits of Anti-Retroviral Therapy;
barriers to using Anti-Retroviral Therapy; threat from the susceptibility to the
illness and the severity; perceived roles in treatment; and the negative
behaviours of healthcare providers. CONCLUSION: The findings provide useful
insights to inform Nigeria's health policies on Anti-Retroviral Therapy. There is
a need to educate the women on the benefits of the treatment as well as how they
can cope with side effects and the daily regimen of the therapy during pregnancy.
The findings also indicate the need for training healthcare providers on
facilitative patient-provider relationship.
PMID- 29954690
TI - Location of Metastases in Contemporary Prostate Cancer Patients Affects Cancer
Specific Mortality.
AB - PURPOSE: To quantify the prognostic effect of the location of prostate cancer
(PCa) metastases on cancer-specific mortality (CSM) and the rate of other-cause
mortality (OCM) in contemporary newly diagnosed metastatic PCa (mPCa) patients.
PATIENTS AND METHODS: Within the Surveillance Epidemiology and End Results
database (2004-2014), we focused on newly diagnosed mPCa patients. Data were
stratified according to the site of metastases and age group. Cumulative
incidence smoothed plots were generated for CSM and OCM at 5 years after
diagnosis, according to the competing-risks methods. Multivariable competing
risks analyses tested the effect of the location of PCa metastases on CSM.
RESULTS: Among 18,404 patients with mPCa, the majority had exclusively bone
metastases (63.6%). At 5 years, CSM rate was 59.7% and OCM rate was 14%.
According to the location of metastases, CSM rates were 44.5%, 57.9%, 67.1%,
62.7%, 66%, and 76.3% for exclusively lymph node (LN), exclusively bone, bone
plus LN, exclusively visceral, visceral plus LN, and visceral plus LN and bone
disease, respectively. In multivariable competing-risks models, PCa-specific
mortality rate was 1.58-, 1.79-, 1.91-, 2.10-, and 2.47-fold higher in patients
with exclusively bone, bone plus LN, exclusively visceral, visceral plus LN, and
visceral plus bone and LN involvement compared to those with exclusively LN
metastases (all P < .001). CONCLUSION: Patients with concomitant visceral, bone,
and LN metastases have the worst prognosis. Similarly, when either bone or
visceral metastases coexist with concomitant LN metastases, CSM rates are higher
than when no concomitant LN metastases are present.
PMID- 29954691
TI - Black lung is still a threat.
PMID- 29954693
TI - Bictegravir/emtricitabine/tenofovir alafenamide, Ibalizumab, and Ozenoxacin.
PMID- 29954692
TI - Eosinophilic Esophagitis Is a Late Manifestation of the Allergic March.
AB - BACKGROUND: The allergic march describes the natural history of allergic
conditions as they develop during childhood. Eosinophilic esophagitis (EoE) is a
chronic allergic inflammatory disease that can be triggered by specific foods.
Despite its allergic pathophysiology, the epidemiologic relationship between EoE
and established members of the allergic march is unknown. OBJECTIVE: We sought to
determine whether EoE meets epidemiologic criteria for being considered a member
of the allergic march. METHODS: Using a primary care birth cohort of 130,435
children, we determined the natural histories of atopic dermatitis (AD), IgE
mediated food allergy (IgE-FA), asthma, EoE, and allergic rhinitis (AR) in
individual patients. We then performed case-control analyses to establish the
extent that existing allergic conditions influence the rate of subsequent EoE
diagnosis. RESULTS: A total of 139 children developed EoE during the observation
period (prevalence of 0.11%). The peak age of EoE diagnosis was 2.6 years, as
compared with 0.3 years, 1 year, 1.1 years, and 2.1 years for AD, IgE-FA, asthma,
and AR, respectively. The presence of AD (hazard ratio [HR] 3.2, 95% confidence
interval [CI] 2.2-4.6), IgE-FA (HR 9.1, 95% CI 6.5-12.6), and asthma (HR 1.9, 95%
CI 1.3-2.7) was independently and cumulatively associated with subsequent EoE
diagnosis. The presence of AR was associated with subsequent EoE diagnosis (HR
2.8, 95% CI 2.0-3.9), and the presence of EoE was associated with subsequent AR
diagnosis (HR 2.5, 95% CI 1.7-3.5). CONCLUSIONS: Allergic comorbidities are
positively associated with EoE diagnosis. Together, our findings suggest that EoE
is a late manifestation of the allergic march.
PMID- 29954694
TI - To mist or not to mist: An update on the recommendations for live-attenuated
influenza vaccine.
PMID- 29954695
TI - Corrections.
PMID- 29954696
TI - HTA and Its Use in Drug Policies: Singapore.
AB - INTRODUCTION: Singapore has a robust health care system that is well known for
delivering good health outcomes. In the public health care sector, subsidies and
financial assistance are provided for drugs listed on the Standard Drug List and
Medication Assistance Fund. Additional financing mechanisms are also available to
provide further support for patients in need. With new technologies entering the
market at high costs, health technology assessment (HTA) is playing an
increasingly important role to inform their relative value and determine how best
to allocate finite health care resources to ensure long-term sustainability of
the health care system. ROLE OF HTA: National HTA efforts are currently focused
on informing subsidy decision making and improving patient access to cost
effective drugs. The Agency for Care Effectiveness (ACE) was established in 2015
to support the Ministry of Health Drug Advisory Committee make evidence-based
recommendations for the public funding of drugs. Standardized HTA methods and
processes have been developed in line with international best practice to ensure
that ACE's evaluations are conducted in a consistent and robust manner. Since
ACE's establishment, subsidies are now provided earlier within a drug's life
cycle, and value-based pricing has led to more cost-effective prices being
negotiated with companies to improve affordability for patients and the public
health care system. CONCLUSION: To achieve greater impact, Singapore needs to
expand its HTA capacity beyond subsidy decision making and drive appropriate care
in a sustainable manner for future generations.
PMID- 29954697
TI - The relationship of IQ and emotional processing with insula volume in
schizophrenia.
AB - OBJECTIVE: The insula is involved in general and social cognition, in particular
emotion regulation. Aim of this study is to investigate whether insula volume is
associated with Intelligence Quotient (IQ) and emotional processing in
schizophrenia patients versus healthy controls (HC). METHODS: Magnetic resonance
imaging (MRI) brain scans, IQ and emotional processing tests (Benton Facial
Recognition Test [BFRT], Degraded Facial Affect Recognition Task [DFAR],
Emotional Mentalizing Task [EMT]) were administered in 246 subjects (133
schizophrenia patients and 113 controls). First order linear regression analyses
were performed with group as independent variable and IQ/emotional processing
test scores as dependent variables. Second order stepwise linear regression
analyses were performed with IQ/emotional processing test scores as independent
variables (as well as intracranial volumes, age, gender and cannabis abuse) and
right/left insula volumes as dependent ones. A final mediation analysis (Sobel
test) was performed to verify if IQ or emotional processing test scores could
explain the eventual differences in insula volumes between the two groups.
RESULTS: Schizophrenia patients presented lower insula volumes (left: F = 9.72, p
< 0.01; right: F = 10.93, p < 0.01) as compared with healthy controls. Smaller
insula volumes in schizophrenia patients are mediated by lower IQ scores (Sobel
tests: 3.07, p < 0.01 for right insula; 2.72, p < 0.01 for left insula), but not
by impairments in emotion processing. CONCLUSIONS: IQ, but not emotional
processing mediates smaller insula volumes in schizophrenia patients.
PMID- 29954698
TI - Impaired associative inference in the early stage of psychosis.
AB - Relational memory is impaired in chronic schizophrenia. It is unclear if similar
deficits are already present in the early stage of psychosis. We used the
Associative Inference Paradigm to test relational memory ability in the early
stage of a non-affective psychotic disorder. Eighty-two early stage psychosis
patients and 67 healthy control subjects were trained on 3 sets of 30 paired
associates: H-F1 (house paired with face), H-F2 (same house paired with new
face), F3-F4 (two new faces). Subjects who reached 80% recall accuracy of the
paired associates during training were then tested for their ability to recall
the previously seen pairs and solve a novel, inferential pairing F1-F2 (faces
linked through association to same house). Sixty early psychosis patients (73%)
and 67 healthy control subjects (100%) successfully reached the accuracy
threshold (80%) during training and were included in the analysis of relational
memory. The early stage psychosis patients showed less of an associative
inference effect than the healthy controls (pair type by group interaction: F
(1,125) = 5.04, p < 0.05). However, the majority of early psychosis patients
(52%) displayed intact inferential memory, compared to our prior study which
revealed just 16% of chronic schizophrenia patients had intact inferential
memory. Patients in the early stage of psychosis show a relational memory
deficit, although less pronounced than in chronic schizophrenia. Longitudinal
studies are needed to examine the progression of relational memory deficits in
schizophrenia and its associations with clinical, functional, and biological
measures.
PMID- 29954699
TI - Neural correlates of global and specific cognitive deficits in schizophrenia.
AB - Cognitive deficits are a core feature of schizophrenia, but the neural mechanisms
that contribute to these characteristics are not fully understood. This study
investigated whether volume of the dorsal lateral prefrontal cortex (DLPFC),
inferior frontal gyrus (IFG), hippocampus, and white matter were associated with
impairment in specific cognitive domains, including executive functioning,
working memory, verbal memory, verbal fluency, processing speed, versus global
functioning. The multi-site data used in this study was collected from the
Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP), and
consisted of 206 healthy controls and 247 individuals with either schizophrenia
or schizoaffective disorder. The neuroimaging data was segmented based on the
Destrieux atlas in FreeSurfer. Linear regression analyses revealed that global
cognition, executive functioning, working memory, and processing speed were
associated with all brain structures, except the DLPFC was only associated with
executive fucntion. When controlling for the global cognitive deficit, executive
function was trending significance with white matter, but continued to be
associated with the DLPFC and IFG, as did the association between processing
speed and the hippocampus. These findings suggest that volumes of the DLPFC, IFG,
hippocampus, and white matter are associated with the global cognitive impairment
seen in schizophrenia, but some brain structures may also be specifically related
to domain-specific deficits (primarily executive function) over-and-beyond the
global cognitive deficit.
PMID- 29954700
TI - Self-esteem moderates affective and psychotic responses to social stress in
psychosis: A virtual reality study.
AB - BACKGROUND: Higher liability to psychosis is associated with low self-esteem and
increased sensitivity to social stress. Recently, we reported a positive relation
between liability to psychosis and affective and psychotic responses to social
stress. This study investigated how self-esteem moderates paranoia, peak
subjective distress and stress reactivity of people with different psychosis
liability in response to social stressors in virtual reality. METHODS: Ninety
four individuals with lower (41 siblings and 53 controls) and 75 persons with
higher psychosis liability (55 with recent onset psychotic disorder and 20 at
ultra-high risk for psychosis) explored five times a virtual cafe with various
social stressors (crowdedness, ethnic minority status, and hostility). They rated
momentary paranoia (State Social Paranoia Scale) after each experiment and
subjective distress on a visual analogue scale before and after the experiments.
Positive and negative self-esteem were assessed with the Self-Esteem Rating
Scale. RESULTS: Momentary paranoia, peak subjective distress, and reactivity to
social stressors were associated with negative self-esteem, but not positive self
esteem. Effects of both positive and negative self-esteem on psychotic and
affective stress responses, but not stress reactivity, became significantly
stronger when individuals were exposed to more stressful environments. Effects of
self-esteem on momentary paranoia and peak subjective distress did not differ
between the high liability and low liability group. Persons with lower psychosis
liability had a stronger effect of negative self-esteem on stress reactivity than
persons with higher liability. CONCLUSIONS: Positive and negative self-esteem may
play an important role in affective and psychotic responses to social stress.
PMID- 29954701
TI - Improving working memory in schizophrenia: Effects of 1 mA and 2 mA transcranial
direct current stimulation to the left DLPFC.
AB - Deficits in various cognitive processes, such as working memory, are
characteristic for schizophrenia, lowering patients' functioning and quality of
life. Recent research suggests that transcranial direct stimulation (tDCS)
applied to the dorsolateral prefrontal cortex (DLPFC) may be a potential
therapeutic intervention for cognitive deficits in schizophrenia. Here, we
examined the effects of online tDCS to the DLPFC on working memory (WM)
performance in 40 schizophrenia patients in two separate experiments with a
double blind, sham-controlled, cross-over design. Patients underwent single
sessions of active and sham tDCS in a randomized order. Stimulation parameters
were anode F3, cathode right deltoid muscle, 21 min tDCS duration, 1 mA tDCS in
Experiment 1 (N = 20) and 2 mA tDCS in Experiment 2 (N = 20). Primary outcome was
the change in WM performance as measured by a verbal n-back paradigm (1- to 3
back). Irrespective of the stimulation intensity, data analysis showed a
significant higher WM accuracy during active tDCS than during sham tDCS (p =
0.019), but no main effect of stimulation intensity (p = 0.392). Subsequent
separate analyses revealed a significantly improved WM performance only during 1
mA (p = 0.048). TDCS facilitated WM functioning in schizophrenia, with an
advantage of 1 mA over 2 mA. Our results support the notion that tDCS may be a
potential treatment for cognitive deficits in schizophrenia and emphasize the
need for future research on the specific stimulation parameters.
PMID- 29954702
TI - Effects of bilateral prefrontal rTMS on brain activation during social-emotional
evaluation in schizophrenia: A double-blind, randomized, exploratory study.
AB - This exploratory study reports on the effects of Repetitive Transcranial Magnetic
Stimulation (rTMS) on (prefrontal) brain activity changes during ambiguous
emotional evaluation in patients with schizophrenia. Before and after randomly
assigned treatment with active and sham rTMS, patients performed the Wall of
Faces task during fMRI scanning. fMRI analysis showed that rTMS treatment
resulted in reduced activation of striato-fronto-parietal brain areas, while
activation increased compared to baseline after sham. Thus, prefrontal rTMS may
normalize an increased brain response to ambiguous emotional stimuli, but future
studies should confirm these findings.
PMID- 29954703
TI - Schizophrenia is associated with an increased risk of sexually transmitted
infections: A nationwide population-based cohort study in Taiwan.
AB - OBJECTIVES: In Taiwan, there has been a growing emphasis on physical health
screening, health education and improving access to treatment in patients with
schizophrenia (SCZ). However, sexual health needs, including screening and
prevention of sexually transmitted infections (STI), are neglected in this
population. The study aimed to investigate the association between SCZ and the
subsequent incident STI and to examine potential risk factors. METHODS: Using the
National Health Insurance Research Database of Taiwan, 58,948 SCZ patients and
235,784 controls matched by gender and age were enrolled between 2000 and 2010
and followed until the end of 2011. Participants who developed any STI (HIV,
syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis)
during the follow-up period were identified. Cox regression analysis was
performed to examine the risk of STI between SCZ patients and controls. RESULTS:
SCZ patients were predisposed to developing STI (hazard ratio (HR): 1.11, 95%
confidence interval (95% CI): 1.01-1.21) that could be caused by syphilis (HR:
2.58, 95% CI: 2.14-3.10) or possibly HIV (Crude HR: 1.39, 95% CI: 1.04-1.86;
adjusted HR: 1.11, 95% CI: 0.81-1.52). Additionally, this study found that
female, young adults, low-income, living in less urbanized areas, and comorbid
substance abuse were potential risk factors for developing STI. CONCLUSION: This
study shows that SCZ is associated with an increased risk of developing STI,
which has direct implications for the development of targeted prevention
interventions or regular sexual health screening in mental health clinics to
reduce the disproportionate burden of HIV and other STI in SCZ patients.
PMID- 29954704
TI - Sensitivity and specificity of hypoactivations and failure of de-activation in
schizophrenia.
AB - BACKGROUND: Brain functional changes reported in schizophrenia include reduced
prefrontal cortex activation (hypofrontality), increased frontal activation
(hyperfrontality) and failure of de-activation in the medial frontal cortex. The
relative importance of these changes is unestablished. METHODS: A 'discovery'
sample of 32 schizophrenic patients and 32 controls was used to establish regions
of altered activation and de-activation in the patients. The discriminatory power
of these regions was examined using receiver-operator characteristics (ROC)
analysis in two 'test' samples, one of 83 patients with chronic schizophrenia and
83 healthy controls, and the other of 31 first-episode patients and 31 healthy
controls. RESULTS: The discovery sample revealed reduced activation in the
prefrontal cortex and other regions, and failure of de-activation in the medial
frontal cortex. Failure of de-activation had significantly greater power to
distinguish the chronic patients from the healthy controls than hypoactivation.
The pattern was similar in the first-episode patients, where additionally the
discriminatory power of hypoactivation was poor. Controlling for the effects of n
back task performance tended to reduce discriminatory power overall, but this
persisted for failure of de-activation in the chronic test sample. CONCLUSIONS:
Both hypoactivation and failure of de-activation can distinguish patients with
chronic schizophrenia from healthy subjects, but the latter abnormality has more
power. Failure of de-activation cannot be construed simply as a passive
consequence of reduced prefrontal activation in the disorder.
PMID- 29954705
TI - Co-occurrence of heterozygous CREB3L3 and APOA5 nonsense variants and polygenic
risk in a patient with severe hypertriglyceridemia exacerbated by estrogen
administration.
AB - We describe a case of a 36-year-old woman with severe hypertriglyceridemia likely
caused by double heterozygosity of a known pathogenic APOA5 nonsense variant
(p.Q275X) and a novel CREB3L3 nonsense variant (p.C296X) on a background of very
strong polygenic susceptibility. Her clinical course worsened with development of
eruptive xanthomata after oral administration of 2 mg estradiol twice daily for 2
weeks as part of a medical protocol for intrauterine embryo transfer following in
vitro fertilization. Her triglyceride levels decreased to baseline and xanthomata
resolved without treatment after discontinuation of hormonal therapy, which also
resulted in termination of pregnancy. Before undergoing a second embryo transfer
using her natural cycle and no exogenous hormones, the patient started
combination therapy with eicosapentaenoic acid ethyl ester and gemfibrozil,
leading to an ~80% decrease in triglyceride levels. She continued treatment
throughout pregnancy, which progressed to term with the delivery of healthy
twins.
PMID- 29954706
TI - Professional resilience among nurses working in an overcrowded emergency
department in Taiwan.
AB - PURPOSE: Professional resilience has become increasingly important for nurses in
adverse work environments to reduce the negative results and increase the
positive outcomes of stress. This study aimed to explore and understand the
experiences of resilience among nurses in an overcrowded emergency department
(ED) and increase knowledge about what nurses identified as protective factors,
which may be useful for future planning. METHODS: A construction-grounded theory
(CGT) approach was adopted. Purposive sampling and snowball technique were
employed to recruit 13 participants, which proved sufficient to achieve
theoretical saturation. In-depth interviews were conducted and audiotaped.
RESULTS: Doubting work value and maintaining optimism were the 2 main themes in
the core category of seeing and taking work difficulty and responsibility. Nurses
described how their passion for their profession gradually diminished, but they
assessed the situation and took responsibility for their jobs. CONCLUSION: This
study found that nurses retain their compassion, which sustains them in their
work. The issue of ED overcrowding led to pessimism among nurses. However, work
rewards encouraged nurses to adopt a more proactive attitude toward work-related
adversity.
PMID- 29954707
TI - Long-acting injectable antipsychotics for the treatment of schizophrenia in
Spain.
AB - Antipsychotics are an essential component in the treatment of schizophrenia. Long
acting injectable formulations (LAI) arose to improve adherence with the
associated potential of reducing the risk of relapse. The objective of this
article is to analyze the use of LAI antipsychotics in Spain, which is similar to
other European countries but with a predominance of the use of second generation
LAI, to discuss the possible causes of prescribing differences with respect to
other countries (including organizational aspects, attitudes of psychiatrists,
patients and family members, and clinical practice guidelines), and to discuss
their use in acute psychiatric units, first episode, and in children and
adolescents. In our view, while it is necessary to increase existing evidence
regarding the advantages of LAI antipsychotics and the differentiation between
LAI antipsychotics currently available, their use will likely continue to grow
driven by clinical experience.
PMID- 29954708
TI - Correlation between parameters of volumetric capnography and spirometry during a
submaximal exercise protocol on a treadmill in patients with cystic fibrosis and
healthy controls.
AB - INTRODUCTION: Spirometry is the most frequently used test to evaluate the
progression of lung damage in cystic fibrosis (CF). However, there has been low
sensitivity in detecting early lung changes. In this context, our objective was
to identify the correlation between parameters of volumetric capnography (VCap)
and spirometric parameters during a submaximal treadmill exercise test. METHODS:
A cross-sectional and controlled study which included 64 patients with CF (CFG)
and 64 healthy control subjects (CG) was performed. The CFG was from a university
hospital and the CG from local schools. All participants underwent spirometry and
VCap before, during and after the submaximal treadmill exercise test. The main
variable analyzed by VCap was the slope of phase 3 (slope 3), which indicates the
[exhaled carbon dioxide] at the end of expiration, and expresses the
heterogeneity of gas emptying in pulmonary periphery. The correlation analysis
between spirometry and VCap was conducted using the Spearman correlation test,
considering alpha=0.05. RESULTS: The indices analyzed by VCap showed correlation
with parameters of VCap. Slope 3 showed an inverse correlation with forced
expiratory volume in the first second of forced vital capacity (FEV1) in both
groups and at all moments of the submaximal treadmill exercise test. Forced vital
capacity (FVC) and FEV1/FVC ratio showed an inverse correlation with slope 3 only
for CFG. Values of slope 3 corrected by the spontaneous tidal volume (VT) and end
tidal carbon dioxide tension (PetCO2) showed results similar to slope 3 analyzed
separately. CONCLUSION: Parameters of VCap such as slope 3, slope 3/VT and slope
3/PetCO2 correlated with sensitive variables of spirometry such as FEV1, FVC and
FEV1/FVC ratio. For the evaluated variables, there was consistency in the
correlation between the two tests, which may indicate the impact of CF on
pulmonary physiology.
PMID- 29954709
TI - Moral Goodness Is the Essence of Personal Identity.
PMID- 29954710
TI - If You Become Evil, Do You Die?
PMID- 29954711
TI - Comparison of serum lipid profile in type 2 diabetes with and without adequate
diabetes control in Sudanese population in north of Sudan.
AB - BACKGROUND: Diabetes mellitus (DM) is a major health problem in Sudan and is a
leading cause of morbidity and mortality. Dyslipidemia is a major complication of
diabetes and an important risk factor for cardiovascular disease (CVD). The
objective of this study was to determine the prevalence of dyslipidemia and its
co-relation with the glycemic control in individuals with diabetes in River Nile
State, Sudan. METHODS: Individuals with diabetes attended, Naserudin Karamalla
Diabetic (NKDM) Centre, in Atbara teaching hospital during study period, who
volunteered to participate were included. Only those on treatment for DM for at
least one year were included. Venous samples were collected for cholesterol,
triglycerides, HDL, LDL, blood glucose and Glycosylated hemoglobin. Participants
were interviewed using standardized pretested questionnaire to record medical
history and sociodemographic characteristics. Blood pressure, body mass index
(BMI) and waist circumference were measured. RESULTS: A total of 188 individuals
were included. The mean age was 49.5 + 13.9 and (128) 68.1% were females. Most
patients were having DM for at least 3-5 years 69 (36.7%). Poor diabetes control
(HbA1c >7) was recorded in 87.2%, hypercholesterolemia, hypertriglyceridemia and
high LDL were identified in 36.6%, 27.7% and 26.6% respectively. In addition, HDL
was low in 61.2% of patients. CONCLUSION: Low HDL is a prominent feature in two
thirds of individuals with diabetes, while high cholesterol and high triglyceride
were seen in over one quarter.
PMID- 29954712
TI - Lessons Learned From a Feasibility Study Delivered in 2 WIC Sites to Promote
Physical Activity Among Pregnant Latinas.
AB - OBJECTIVE: To assess the feasibility, including demand for and acceptability of a
physical activity (PA) intervention among pregnant Latinas recruited at the
Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).
METHODS: Women <20 weeks gestation and self-reporting <150 minutes of PA/wk were
recruited from 2 WIC locations in Southern California. The 9-wk, promotora-led
intervention included 1-hour sessions and 2 walking groups/wk. RESULTS: WIC was
supportive of recruitment, intervention, and evaluation activities. Of an
estimated pool of 525 women at <20 wks gestation, 141 expressed interest, 108
were screened for eligibility, and 21 were enrolled. Of the 21 who enrolled, 12
completed the postintervention assessment (7 in the participant group and 5 in
the nonparticipant group). CONCLUSIONS AND IMPLICATIONS: Demand and acceptability
will need to be improved before this intervention can be considered feasible,
potentially by extending eligibility and improving access to intervention.
PMID- 29954713
TI - Assessing Physical Activity, Fruit, Vegetable, and Sugar-Sweetened Beverage
Intake Patterns of College Students in Kansas.
AB - OBJECTIVE: To test the effectiveness of a 15-month intervention for reducing
sugar-sweetened beverage (SSB) intake among college students and assess fruit and
vegetable (F/V) intake and physical activity (PA) habits and their relationship
to SSB intake. DESIGN: Randomized, controlled study. PARTICIPANTS: A total of 156
college students (aged 18-24 years) from a Kansas university, mostly female
(72%), white (89%), and freshmen (51%). INTERVENTION: Two-staged intervention
included participants receiving: (1) 3 weekly stage-tailored messages on
healthful behaviors for 10 weeks; and (2) 3 monthly stage-tailored messages and 1
monthly e-mail encouraging a visit to the portal page, after the 3-month physical
assessment. MAIN OUTCOME MEASURE(S): Stages of change for PA and F/V intake, self
reported PA scores, self-reported F/V intake, and SSB intake habits. ANALYSIS:
Generalized linear mixed models and linear regression models were used to test
changes and associations among outcome measures. RESULTS: No significant decrease
occurred in SSB consumption (P > .05) among intervention participants. Both
control and intervention groups recorded low F/V intake and moderate PA scores.
CONCLUSIONS AND IMPLICATIONS: Low F/V intake and high SSB intake evident among
study participants may pose risk for unwanted weight gain and obesity-related
conditions. Furthermore, college campuses can continue to support an environment
conducive for being physically active, while promoting healthy eating behaviors.
PMID- 29954714
TI - Parents Report Competing Priorities Influence Snack Choice in Youth Sports.
AB - OBJECTIVE: To describe parental perceptions of team snacks, factors that motivate
snack choice, and perceptions of healthy snacking guidelines in youth sports.
METHODS: Six in-depth group interviews were conducted among parents (n = 22) of
children aged 4-12 years in 2 Los Angeles County Baseball Little Leagues.
Interviews were audio-recorded, transcribed, and analyzed using thematic
analysis. RESULTS: Parents perceived fruit as the ideal snack; this ideal was
balanced with competing priorities, including children's preferences, cost, time,
and social norms regarding snacks as rewards and team bonding. Although parents
were supportive of promoting healthy snacks, they believed that snacking
guidelines should not be mandated. CONCLUSIONS AND IMPLICATIONS: Developing
messages that align with parents' motivations when choosing snacks could promote
healthier snacking in youth sports. Future studies are warranted to explore
drivers of snacking with a broader sample and to examine how to promote healthy
snacks effectively.
PMID- 29954716
TI - On the Protective Effects of Gene SNPs Against Human Cancer.
PMID- 29954715
TI - Latino Parents' Perceptions of Physical Activity and Healthy Eating: At the
Intersection of Culture, Family, and Health.
AB - OBJECTIVE: To explore Latino parents' perspectives on healthy living and identify
strategies to incorporate in a future child obesity intervention. DESIGN:
Descriptive, qualitative study. SETTING: Participants were recruited from an
emerging Latino community (area with low [ < 5%] yet growing concentrations of
Latinos) in Allegheny County, PA. PARTICIPANTS: Thirty-two parents of preschool
children participated in 5 Spanish-language focus groups. PHENOMENON OF INTEREST:
Parents' perceptions of a healthy lifestyle (ie, physical activity and
nutrition). ANALYSIS: Data were analyzed using the constant comparison method to
identify salient categories, themes, and patterns. RESULTS: Three overarching
themes were identified: (1) Healthy Living: Beyond One's Control; (2) Estamos
Acostumbrados [We Are Used to a Certain Lifestyle]; and (3) Latin American and US
Culture Conflict. In general, parents perceived maintaining a healthy lifestyle
to require enormous effort and that change was difficult given a lack of
knowledge and control. CONCLUSIONS AND IMPLICATIONS: Key intervention approaches
with this population may include a focus on the family environment. Increasing
knowledge, building self-efficacy, and modeling behavior through family recipe
preparation and physical activity breaks may be necessary, as well as an emphasis
on and orientation to community resources to support behavior change and physical
activity and healthy eating habits.
PMID- 29954717
TI - Does physiotherapy prehabilitation improve pre-surgical outcomes and influence
patient expectations prior to knee and hip joint arthroplasty?
AB - INTRODUCTION: Evidence supporting physiotherapy prior to hip or knee replacement
for decreasing pain and improving function pre and post-operatively is equivocal.
This observational cohort study used a mixed-methods approach to investigate
whether 8 weeks of physiotherapy led exercise and education ('prehabilitation')
would change pain and functional outcomes prior to surgery, and if patients'
expectations and satisfaction post-surgery were influenced. METHODS: Participants
awaiting THR or TKR were recruited (n = 75). Fifty two opted into the
'prehabilitation' group while twenty three opted for usual care. The
prehabilitation group included a 45 min exercise and 15 min education session
twice weekly for 8 weeks. All participants completed the WOMAC, NRS, Health
Thermometer, 5xSTS and TUG outcome measures. Data were collected before and after
prehabilitation and 6 weeks after surgery. Qualitative data were collected from
22 participants via telephone interviews and analysed inductively. RESULTS: Both
groups improved post surgery. The prehabilitation group showed statistically
significant improvements in all outcome measures after prehabilitation (pre
surgery). Participants' felt prehabilitation prepared them well for surgery and
influenced expectations post-operatively. Group education talks and the
experience of friends and family appeared highly valued information sources.
CONCLUSION: Prehabilitation improved patients' pain and function before hip or
knee replacement surgery.
PMID- 29954718
TI - Phenotype-modifying Factors in Hypertrophic Cardiomyopathy. Response.
PMID- 29954719
TI - Device to Narrow the Coronary Sinus in Refractory Angina.
PMID- 29954720
TI - Annual Incidence of Confirmed Stent Thrombosis and Clinical Predictors in
Patients With ACS Treated With Ticagrelor or Prasugrel.
AB - INTRODUCTION AND OBJECTIVES: There is little evidence on rates of stent
thrombosis (ST) in patients receiving dual antiplatelet therapy (DAPT) with
ticagrelor or prasugrel. The aim of this study was to analyze the incidence and
predictors of ST after an acute coronary syndrome among patients receiving DAPT
with ticagrelor vs prasugrel. METHODS: We used data from the RENAMI registry
(REgistry of New Antiplatelet therapy in patients with acute Myocardial
Infarction), analyzing a total of 4123 acute coronary syndrome patients
discharged with DAPT with ticagrelor or prasugrel in 11 centers in 6 European
countries. The endpoint was definite ST within the first year. A competitive risk
analysis was carried out using a Fine and Gray regression model, with death being
the competitive event. RESULTS: A total of 2604 patients received DAPT with
ticagrelor and 1519 with prasugrel; ST occurred in 41 patients (1.10%), with a
similar cumulative incidence between ticagrelor (1.21%) and prasugrel (0.90%).
The independent predictors of ST were age (sHR, 1.03; 95%CI, 1.01-1.06), ST
segment elevation (sHR, 2.24; 95%CI, 1.22-4.14), previous myocardial infarction
(sHR, 2.56; 95%CI, 1.19-5.49), and serum creatinine (sHR, 1.29; 95%CI, 1.08
1.54). CONCLUSIONS: Stent thrombosis is infrequent in patients receiving DAPT
with ticagrelor or prasugrel. The variables associated with an increased risk of
ST were advanced age, ST segment elevation, previous myocardial infarction, and
serum creatinine.
PMID- 29954722
TI - Splenic rupture from babesiosis, an emerging concern? A systematic review of
current literature.
AB - Babesiosis is a relatively common tick-borne parasitic infection of erythrocytes
primarily affecting the northeastern United States. Babesiosis' prevalence and
presentation have earned it the monikers "malaria of the northeast" and
"Nantucket fever". Clinical presentation ranges from asymptomatic infection to
severe infection including acute respiratory distress syndrome (ARDS) and
disseminated intravascular coagulopathy (DIC) or death. Since 2008, there have
been a number of reports of splenic rupture in patients with the disease. We seek
to provide a further understanding of this process, with the report of a case of
splenic rupture followed by a systematic review of the current literature. We
found that 87% of splenic rupture secondary to babesiosis occurred in male
patients who are otherwise healthy, with an average of 56 years. Computed
tomography is a reliable mode of diagnosis, and hemoperitoneum is the most common
imaging finding. Patients with splenic rupture due to human babesiosis were
successfully treated by various management strategies, such as conservative non
operative approach, splenic artery embolization, and splenectomy. The modality of
treatment depends on patient's clinical course and hemodynamic stability,
although spleen conserving strategy should be considered first whenever possible.
PMID- 29954721
TI - Procedural, Functional and Prognostic Outcomes Following Recanalization of
Coronary Chronic Total Occlusions. Results of the Iberian Registry.
AB - INTRODUCTION AND OBJECTIVES: There is current controversy regarding the benefits
of percutaneous recanalization (PCI) of chronic total coronary occlusions (CTO).
Our aim was to determine acute and follow-up outcomes in our setting. METHODS:
Two-year prospective registry of consecutive patients undergoing PCI of CTO in 24
centers. RESULTS: A total of 1000 PCIs of CTO were performed in 952 patients.
Most were symptomatic (81.5%), with chronic ischemic heart disease (59.2%).
Previous recanalization attempts had been made in 15%. The mean SYNTAX score was
19.5 +/- 10.6 and J-score was > 2 in 17.3%. A retrograde procedure was performed
in 92 patients (9.2%). The success rate was 74.9% and was higher in patients
without previous attempts (82.2% vs 75.2%; P = .001), those with a J-score <= 2
(80.5% vs 69.5%; P = .002), and in intravascular ultrasound-guided PCI (89.9% vs
76.2%, P = .001), which was an independent predictor of success. In contrast,
severe calcification, length > 20mm, and blunt proximal cap were independent
predictors of failed recanalization. The rate of procedural complications was
7.1%, including perforation (3%), myocardial infarction (1.3%), and death (0.5%).
At 1-year of follow-up, 88.2% of successfully revascularized patients showed
clinical improvement (vs 34.8%, P < .001), which was associated with lower
mortality. At 1-year of follow-up, the mortality rate was 1.5%. CONCLUSIONS:
Compared with other national registries, patients in the Iberian registry
undergoing PCI of a CTO showed similar complexity, success rate, and
complications. Successful recanalization was strongly associated with functional
improvement, which was related to lower mortality.
PMID- 29954723
TI - Association Between Self-Reported and Objective Activity Levels by Demographic
Factors: Ecological Momentary Assessment Study in Children.
AB - BACKGROUND: To address the limitations of the retrospective self-reports of
activity, such as its susceptibility to recall bias, researchers have shifted
toward collecting real-time activity data on mobile devices via ecological
momentary assessment (EMA). Although EMA is becoming increasingly common, it is
not known how EMA self-reports of physical activity and sedentary behaviors
relate to the objective measures of activity or whether there are factors that
may influence the strength of association between these two measures.
Understanding the relationship between EMA and accelerometry can optimize future
instrument selection in studies assessing activity and health outcomes.
OBJECTIVE: The aim of this study was to examine the associations between EMA
reported sports or exercise using the accelerometer-measured moderate-to-vigorous
physical activity (MVPA) and EMA-reported TV, videos, or video games with the
accelerometer-measured sedentary time (ST) in children during matched 2-h windows
and test potential moderators. METHODS: Children (N=192; mean age 9.6 years;
94/192, 49.0% male; 104/192, 54.2% Hispanic; and 73/192, 38.0% overweight or
obese) wore an accelerometer and completed up to 7 EMA prompts per day for 8 days
during nonschool time, reporting on past 2-h sports or exercise and TV, videos,
or video games. Multilevel models were used to assess the relationship between
the accelerometer-measured ST and EMA-reported TV, videos, or video games. Given
the zero-inflated distribution of MVPA, 2-part models were used assess the
relationship between the accelerometer-measured MVPA and EMA-reported sports or
exercise. RESULTS: EMA-reported TV, videos, or video games were associated with a
greater accelerometer-measured ST (beta=7.3, 95% CI 5.5 to 9.0, P<.001). This
relationship was stronger in boys (beta=9.9, 95% CI 7.2 to 12.6, P<.001) than
that in girls (beta=4.9, 95% CI 2.6 to 7.2, P<=.001). EMA-reported sports or
exercise was associated with a greater accelerometer-measured MVPA (zero portion
P<.001; positive portion P<.001). This relationship was stronger on weekends, in
older children, and in non-Hispanic children (zero portion all P values<.001;
positive portion all P values<.001). CONCLUSIONS: EMA reports highly relate to
accelerometer measures. However, the differences in the strength of association
depending on various demographic characteristics suggest that future research
should use both EMA and accelerometers to measure activity to collect
complementary activity data.
PMID- 29954724
TI - Adverse Drug Event Reporting From Clinical Care: Mixed-Methods Analysis for a
Minimum Required Dataset.
AB - BACKGROUND: Patients commonly transition between health care settings, requiring
care providers to transfer medication utilization information. Yet, information
sharing about adverse drug events (ADEs) remains nonstandardized. OBJECTIVE: The
objective of our study was to describe a minimum required dataset for clinicians
to document and communicate ADEs to support clinical decision making and improve
patient safety. METHODS: We used mixed-methods analysis to design a minimum
required dataset for ADE documentation and communication. First, we completed a
systematic review of the existing ADE reporting systems. After synthesizing
reporting concepts and data fields, we conducted fieldwork to inform the design
of a preliminary reporting form. We presented this information to clinician end
user groups to establish a recommended dataset. Finally, we pilot-tested and
refined the dataset in a paper-based format. RESULTS: We evaluated a total of
1782 unique data fields identified in our systematic review that describe the
reporter, patient, ADE, and suspect and concomitant drugs. Of these, clinicians
requested that 26 data fields be integrated into the dataset. Avoiding the need
to report information already available electronically, reliance on prospective
rather than retrospective causality assessments, and omitting fields deemed
irrelevant to clinical care were key considerations. CONCLUSIONS: By attending to
the information needs of clinicians, we developed a standardized dataset for
adverse drug event reporting. This dataset can be used to support communication
between care providers and integrated into electronic systems to improve patient
safety. If anonymized, these standardized data may be used for enhanced
pharmacovigilance and research activities.
PMID- 29954726
TI - Data-Driven Learning in High-Resolution Activity Sampling From Patients With
Bipolar Depression: Mixed-Methods Study.
AB - BACKGROUND: Behavioral activation is a pen and paper-based therapy form for
treating depression. The patient registers their activity hourly, and together
with the therapist, they agree on a plan to change behavior. However, with the
limited clinical personnel, and a growing patient population, new methods are
needed to advance behavioral activation. OBJECTIVE: The objectives of this paper
were to (1) automatically identify behavioral patterns through statistical
analysis of the paper-based activity diaries, and (2) determine whether it is
feasible to move the behavioral activation therapy format to a digital solution.
METHODS: We collected activity diaries from seven patients with bipolar
depression, covering in total 2,480 hours of self-reported activities. A pleasure
score, on a 1-10 rating scale, was reported for each activity. The activities
were digitalized into 6 activity categories, and statistical analyses were
conducted. RESULTS: Across all patients, movement-related activities were
associated with the highest pleasure score followed by social activities. On an
individual level, through a nonparametric Wilcoxon Signed-Rank test, one patient
had a statistically significant larger amount of spare time activities when
feeling bad (z=-2.045, P=.041). Through a within-subject analysis of covariance,
the patients were found to have a better day than the previous, if that previous
day followed their diurnal rhythm (rho=.265, P=.029). Furthermore, a second-order
trend indicated that two hours of daily social activity was optimal for the
patients (beta2=-0.08, t (63)=-1.22, P=.23). CONCLUSIONS: The data-driven
statistical approach was able to find patterns within the behavioral traits that
could assist the therapist in as well as help design future technologies for
behavioral activation.
PMID- 29954725
TI - Tutorial for Using Control Systems Engineering to Optimize Adaptive Mobile Health
Interventions.
AB - BACKGROUND: Adaptive behavioral interventions are individualized interventions
that vary support based on a person's evolving needs. Digital technologies enable
these adaptive interventions to function at scale. Adaptive interventions show
great promise for producing better results compared with static interventions
related to health outcomes. Our central thesis is that adaptive interventions are
more likely to succeed at helping individuals meet and maintain behavioral
targets if its elements can be iteratively improved via data-driven testing (ie,
optimization). Control systems engineering is a discipline focused on decision
making in systems that change over time and has a wealth of methods that could be
useful for optimizing adaptive interventions. OBJECTIVE: The purpose of this
paper was to provide an introductory tutorial on when and what to do when using
control systems engineering for designing and optimizing adaptive mobile health
(mHealth) behavioral interventions. OVERVIEW: We start with a review of the need
for optimization, building on the multiphase optimization strategy (MOST). We
then provide an overview of control systems engineering, followed by attributes
of problems that are well matched to control engineering. Key steps in the
development and optimization of an adaptive intervention from a control
engineering perspective are then summarized, with a focus on why, what, and when
to do subtasks in each step. IMPLICATIONS: Control engineering offers exciting
opportunities for optimizing individualization and adaptation elements of
adaptive interventions. Arguably, the time is now for control systems engineers
and behavioral and health scientists to partner to advance interventions that can
be individualized, adaptive, and scalable. This tutorial should aid in creating
the bridge between these communities.
PMID- 29954727
TI - The Social Effects of Exergames on Older Adults: Systematic Review and Metric
Analysis.
AB - BACKGROUND: Recently, many studies have been conducted to investigate the effects
of exergames on the social well-being of older adults. OBJECTIVE: The aim of this
paper is to synthesize existing studies and provide an overall picture on the
social effects of exergames on older adults. METHODS: A comprehensive literature
search with inclusive criteria was conducted in major social science
bibliographic databases. The characteristics of exergames, participants,
methodology, as well as outcome measurements were extracted from the relevant
studies included in the review. The bibliometric and altmetric outreach of the
included studies were also investigated. RESULTS: A total of 10 studies were
included in the review, with 8 studies having used the Nintendo Wii platform.
Most of the studies recruited healthy older adults from local communities or
senior activity centers. Three groups of social-related outcomes have been
identified, including emotion-related, behavior-related, and attitude-related
outcomes. A metric analysis has shown that the emotion-related and behavior
related outcomes received high attention from both the academic community and
social media platforms. CONCLUSIONS: Overall, the majority of exergame studies
demonstrated promising results for enhanced social well-being, such as reduction
of loneliness, increased social connection, and positive attitudes towards
others. The paper also provided implications for health care researchers and
exergame designers.
PMID- 29954728
TI - Implementation of a Cardiogenic Shock Team and Clinical Outcomes (INOVA-SHOCK
Registry): Observational and Retrospective Study.
AB - BACKGROUND: The development and implementation of a Cardiogenic Shock initiative
focused on increased disease awareness, early multidisciplinary team activation,
rapid initiation of mechanical circulatory support, and hemodynamic-guided
management and improvement of outcomes in cardiogenic shock. OBJECTIVE: The
objectives of this study are (1) to collect retrospective clinical outcomes for
acute decompensated heart failure cardiogenic shock and acute myocardial
infarction cardiogenic shock, and compare current versus historical survival
rates and clinical outcomes; (2) to evaluate Inova Heart and Vascular Institute
site specific outcomes before and after initiation of the Cardiogenic Shock team
on January 1, 2017; (3) to compare outcomes related to early implementation of
mechanical circulatory support and hemodynamic-guided management versus
historical controls; (4) to assess survival to discharge rate in patients
receiving intervention from the designated shock team and (5) create a clinical
archive of Cardiogenic Shock patient characteristics for future analysis and the
support of translational research studies. METHODS: This is an observational,
retrospective, single center study. Retrospective and prospective data will be
collected in patients treated at the Inova Heart and Vascular Institute with
documented cardiogenic shock as a result of acute decompensated heart failure or
acute myocardial infarction. This registry will include data from patients prior
to and after the initiation of the multidisciplinary Cardiogenic Shock team on
January 1, 2017. Clinical outcomes associated with early multidisciplinary team
intervention will be analyzed. In the study group, all patients evaluated for
documented cardiogenic shock (acute decompensated heart failure cardiogenic
shock, acute myocardial infarction cardiogenic shock) treated at the Inova Heart
and Vascular Institute by the Cardiogenic Shock team will be included. An
additional historical Inova Heart and Vascular Institute control group will be
analyzed as a comparator. Means with standard deviations will be reported for
outcomes. For categorical variables, frequencies and percentages will be
presented. For continuous variables, the number of subjects, mean, standard
deviation, minimum, 25th percentile, median, 75th percentile and maximum will be
reported. Reported differences will include standard errors and 95% CI. RESULTS:
Preliminary data analysis for the year 2017 has been completed. Compared to a
baseline 2016 survival rate of 47.0%, from 2017 to 2018, CS survival rates were
increased to 57.9% (58/110) and 81.3% (81/140), respectively (P=.01 for both).
Study data will continue to be collected until December 31, 2018. CONCLUSIONS:
The preliminary results of this study demonstrate that the INOVA SHOCK team
approach to the treatment of Cardiogenic Shock with early team activation, rapid
initiation of mechanical circulatory support, hemodynamic-guided management, and
strict protocol adherence is associated with superior clinical outcomes: survival
to discharge and overall survival when compared to 2015 and 2016 outcomes prior
to Shock team initiation. What may limit the generalization of these results of
this study to other populations are site specific; expertise of the team, strict
algorithm adherence based on the INOVA SHOCK protocol, and staff commitment to
timely team activation. Retrospective clinical outcomes (acute decompensated
heart failure cardiogenic shock, acute myocardial infarction cardiogenic shock)
demonstrated an increase in current survival rates when compared to pre
Cardiogenic Shock team initiation, rapid team activation and diagnosis and timely
utilization of mechanical circulatory support. TRIAL REGISTRATION:
ClinicalTrials.gov NCT03378739; https://clinicaltrials.gov/ct2/show/NCT03378739
(Archived by WebCite at http://www.webcitation.org/701vstDGd).
PMID- 29954730
TI - Abiraterone-Olaparib Combo Aids Men with mCRPC.
AB - Recent findings from a phase II trial suggest that combining the antiandrogen
abiraterone and the PARP inhibitor olaparib significantly improves progression
free survival among patients with metastatic castration-resistant prostate
cancer, regardless of their homologous recombination repair-mutation status.
PMID- 29954729
TI - Important Design Features of Personal Health Records to Improve Medication
Adherence for Patients with Long-Term Conditions: Protocol for a Systematic
Literature Review.
AB - BACKGROUND: The National Health Service (NHS) England spent L15.5 billion on
medication in 2015. More than a third of patients affected by at least one long
term condition do not adhere to their drug regime. Many interventions have been
trialed to improve medication adherence. One promising innovation is the
electronic personal health record. OBJECTIVE: This systematic literature review
aims to identify the important design features of personal health records to
improve medication adherence for patients with long-term conditions. METHODS:
This protocol follows the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses Protocol (PRISMA-P 2015) statement. The following databases will be
searched for relevant articles: PubMed, Science Direct, BioMed Central,
Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of
Systematic Reviews, and the Cochrane Central Register of Controlled Trials.
Studies published in the last fifteen years, in English, will be included if the
participants are adults who were treated outside the hospital, have the ability
to self-administer their medication, and have at least one long-term condition.
The review will exclude commercial or political sources and papers without
references. Papers that research pediatrics, pregnant, or terminally ill patients
will also be excluded, since their medication management is typically more
complex. RESULTS: One reviewer will screen the included studies, extract the
relevant data, and assess the quality of evidence utilizing the Grading of
Recommendations Assessment, Development, and Evaluation system and the risk of
bias using the Cochrane RevMan tool. The second reviewer will assess the quality
of 25% of the included studies to assess interrater agreement. Any disagreement
will be solved by a third reviewer. Only studies of high and moderate quality
will be included for narrative synthesis. CONCLUSIONS: NHS policy assumes that
increasing usage of personal health records by citizens will reduce demand on
health care services. There is limited evidence, however, that the use of health
apps can improve patient outcomes, and, to our knowledge, this is the first
systematic literature review aiming to identify important design features of the
personal health record which may improve medication adherence in the adult
population with long-term conditions. TRIAL REGISTRATION: PROSPERO
CRD42017060542;
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=60542 (Archived
by WebCite at http://www.webcitation.org/6zeuWXxVh). REGISTERED REPORT
IDENTIFIER: RR1-10.2196/9778.
PMID- 29954731
TI - Roche to Buy Balance of Foundation Medicine.
AB - Three years after taking majority control of Foundation Medicine, the Swiss
pharmaceutical company Roche agreed to pay $2.4 billion for the remainder of the
cancer-focused genetic testing company.
PMID- 29954732
TI - No need to hasten death.
PMID- 29954733
TI - Choosing not to pursue active treatment is different from euthanasia.
PMID- 29954734
TI - A traumatic wrist injury.
PMID- 29954735
TI - Upskill doctors to make the most of new medical technologies, report says.
PMID- 29954736
TI - The Sun Solutions Intervention for Operating Engineers: A Randomized Controlled
Trial.
AB - Background: Because Operating Engineers (heavy equipment operators) are outdoor
workers at risk for skin cancer, interventions are needed to promote sun safety.
The objectives were to determine changes in sunscreen use and sunburning among
Operating Engineers randomized to four conditions in the Sun Solutions study: (i)
education only; (ii) education and text message reminders; (ii) education and
mailed sunscreen; and (iv) education, text message reminders, and mailed
sunscreen.Methods: In this randomized controlled trial, Operating Engineers (N =
357) were recruited at required safety training sessions throughout Michigan
during winter/spring of 2012 to 2013 and provided baseline surveys. The four
interventions were delivered over the summer. Postintervention surveys were
collected in the fall (82.1% follow-up).Results: Sunscreen use improved
significantly from baseline to follow-up in all four conditions (P < 0.05),
except sunscreen use among those receiving education and text message reminders
was only marginally significant (P = 0.07). There were significantly greater
increases in sunscreen use in the two conditions that were mailed sunscreen (P <
0.001). There was a significant decrease in the number of reported sunburns from
baseline to follow-up in all four conditions (P < 0.001), but there were no
significant differences in sunburns among the groups. Participant evaluated the
interventions highly with those who received mailed sunscreen rating the
intervention the highest.Conclusions: Providing proper sun-safety education and
minimizing barriers to sunscreen use can increase sunscreen use and decrease
reported sunburns.Impact: The implementation of the Sun Solutions intervention
may be an effective method to modify skin cancer-related behaviors. Cancer
Epidemiol Biomarkers Prev; 27(8); 864-73. (c)2018 AACR.
PMID- 29954737
TI - Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease
and Atrial Fibrillation in the United States.
AB - BACKGROUND: Patients with end-stage kidney disease (ESKD) on dialysis were
excluded from clinical trials of direct oral anticoagulants for atrial
fibrillation (AF). Recent data have raised concerns regarding the safety of
dabigatran and rivaroxaban, but apixaban has not been evaluated despite current
labeling supporting its use in this population. The goal of this study was to
determine patterns of apixaban use and its associated outcomes in dialysis
dependent patients with ESKD and AF. METHODS: We performed a retrospective cohort
study of Medicare beneficiaries included in the United States Renal Data System
(October 2010 to December 2015). Eligible patients were those with ESKD and AF
undergoing dialysis who initiated treatment with an oral anticoagulant. Because
of the small number of dabigatran and rivaroxaban users, outcomes were only
assessed in patients treated with apixaban or warfarin. Apixaban and warfarin
patients were matched (1:3) based on prognostic score. Differences between groups
in survival free of stroke or systemic embolism, major bleeding, gastrointestinal
bleeding, intracranial bleeding, and death were assessed using Kaplan-Meier
analyses. Hazard ratios (HRs) and 95% CIs were derived from Cox regression
analyses. RESULTS: The study population consisted of 25 523 patients (45.7%
women; 68.2+/-11.9 years of age), including 2351 patients on apixaban and 23 172
patients on warfarin. An annual increase in apixaban prescriptions was observed
after its marketing approval at the end of 2012, such that 26.6% of new
anticoagulant prescriptions in 2015 were for apixaban. In matched cohorts, there
was no difference in the risks of stroke/systemic embolism between apixaban and
warfarin (HR, 0.88; 95% CI, 0.69-1.12; P=0.29), but apixaban was associated with
a significantly lower risk of major bleeding (HR, 0.72; 95% CI, 0.59-0.87;
P<0.001). In sensitivity analyses, standard-dose apixaban (5 mg twice a day;
n=1034) was associated with significantly lower risks of stroke/systemic embolism
and death as compared with either reduced-dose apixaban (2.5 mg twice a day;
n=1317; HR, 0.61; 95% CI, 0.37-0.98; P=0.04 for stroke/systemic embolism; HR,
0.64; 95% CI, 0.45-0.92; P=0.01 for death) or warfarin (HR, 0.64; 95% CI, 0.42
0.97; P=0.04 for stroke/systemic embolism; HR, 0.63; 95% CI, 0.46-0.85; P=0.003
for death). CONCLUSIONS: Among patients with ESKD and AF on dialysis, apixaban
use may be associated with a lower risk of major bleeding compared with warfarin,
with a standard 5 mg twice a day dose also associated with reductions in
thromboembolic and mortality risk.
PMID- 29954739
TI - What are you looking at?
PMID- 29954738
TI - Inhibition of SNAT5 Induces Incretin-Responsive State From Incretin-Unresponsive
State in Pancreatic beta-Cells: Study of beta-Cell Spheroid Clusters as a Model.
AB - beta-Cell-beta-cell interactions are required for normal regulation of insulin
secretion. We previously found that formation of spheroid clusters (called K20
SC) from MIN6-K20 clonal beta-cells lacking incretin-induced insulin secretion
(IIIS) under monolayer culture (called K20-MC) drastically induced incretin
responsiveness. Here we investigated the mechanism by which an incretin
unresponsive state transforms to an incretin-responsive state using K20-SC as a
model. Glutamate production by glucose through the malate-aspartate shuttle and
cAMP signaling, both of which are critical for IIIS, were enhanced in K20-SC. SC
formed from beta-cells deficient for aspartate aminotransferase 1, a critical
enzyme in the malate-aspartate shuttle, exhibited reduced IIIS. Expression of the
sodium-coupled neutral amino acid transporter 5 (SNAT5), which is involved in
glutamine transport, was downregulated in K20-SC and pancreatic islets of normal
mice but was upregulated in K20-MC and islets of rodent models of obesity and
diabetes, both of which exhibit impaired IIIS. Inhibition of SNAT5 significantly
increased cellular glutamate content and improved IIIS in islets of these models
and in K20-MC. These results suggest that suppression of SNAT5 activity, which
results in increased glutamate production, and enhancement of cAMP signaling
endows incretin-unresponsive beta-cells with incretin responsiveness.
PMID- 29954740
TI - Lived experience of Silver-Russell syndrome: implications for management during
childhood and into adulthood.
AB - OBJECTIVE: There is limited information on the psychosocial impact of growing up
with Silver-Russell syndrome (SRS), characterised by slow growth in utero leading
to short stature in adulthood. Such information could aid families in making
difficult treatment decisions and guide management strategies for health
professionals. We aimed to explore the lived experience of people with SRS across
the lifespan. DESIGN/SETTING/PATIENTS: In-depth, semi-structured interviews were
conducted between January 2015 and October 2016 with a sample of 15 adults (six
women) with genetically confirmed SRS from the UK. Qualitative interviews were
transcribed and coded to identify similarities and differences: codes were then
grouped to form overarching themes. RESULTS: Four themes were identified from
participant accounts: (1) appearance-related concerns extending beyond height;
(2) strategies to deal with real and perceived threats; (3) women's experiences
of pain, disability and feeling older than their years; and (4) feeling
overlooked in romantic relationships. These themes show that other factors,
beyond short stature, affect patient well-being and indicate a mismatch between
patient need and healthcare provision. CONCLUSIONS: Challenges in SRS during
childhood and adolescence were central to the psychosocial impact of SRS, and
were not limited to height. These challenges, as well as symptoms such as pain
and fatigue for women, have not previously been documented. To help individuals
with SRS develop strategies to manage psychosocial issues, we recommend
clinicians incorporate psychological services as an integral part of
multidisciplinary teams managing individuals with SRS during childhood,
adolescence and adulthood.
PMID- 29954741
TI - "Doing better, but feeling worse": doctors' 70 year relationship with the NHS-an
essay by Nicholas Timmins.
PMID- 29954743
TI - Role model: Deborah Gill.
PMID- 29954742
TI - Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults.
AB - BACKGROUND: The frequency of cardiac rhythm abnormalities and their risk factors
in community-dwelling adults are not well characterized. METHODS: We determined
the frequency of rhythm abnormalities in the UK Biobank, a national prospective
cohort. We tested associations between risk factors and incident rhythm
abnormalities using multivariable proportional hazards regression. RESULTS: Of
502 627 adults (median age, 58 years [interquartile range, 13]; 54.4% women),
2.35% had a baseline rhythm abnormality. The prevalence increased with age with
4.84% of individuals aged 65 to 73 years affected. During 3 368 332 person-years
of follow-up, 15 906 new rhythm abnormalities were detected (4.72 per 1000 person
years; 95% confidence interval [CI]: 4.65-4.80). Atrial fibrillation (3.11 per
1000 person-years; 95% CI: 3.05-3.17), bradyarrhythmias (0.89 per 1000 person
years; 95% CI: 0.86-0.92), and conduction system diseases (1.06 per 1000 person
years; 95% CI: 1.02-1.09) were more common than supraventricular (0.51 per 1000
person-years; 95% CI: 0.48-0.53) and ventricular arrhythmias (0.57 per 1000
person-years; 95% CI: 0.55-0.60). Older age (hazard ratio [HR]: 2.35 per 10-year
increase; 95% CI: 2.29-2.41; P<0.01), male sex (HR: 1.83; 95% CI: 1.76-1.89;
P<0.01), hypertension (HR: 1.49; 95% CI: 1.44-1.54; P<0.01), chronic kidney
disease (HR: 1.95; 95% CI: 1.67-2.27; P<0.01), and heart failure (HR: 1.99; 95%
CI: 1.76-2.26; P<0.01) were associated with new rhythm abnormalities.
CONCLUSIONS: The frequency of rhythm abnormalities in middle-aged to older
community-dwelling adults is substantial. Atrial fibrillation, bradyarrhythmias,
and conduction system diseases account for most rhythm conditions.
PMID- 29954744
TI - Presentation, Clinical Profile, and Prognosis of Young Patients With Myocardial
Infarction With Nonobstructive Coronary Arteries (MINOCA): Results From the VIRGO
Study.
AB - BACKGROUND: We compared the clinical characteristics and outcomes of young
patients with myocardial infarction with nonobstructive coronary arteries
(MINOCA) versus obstructive disease (myocardial infarction due to coronary artery
disease [MI-CAD]) and among patients with MINOCA by sex and subtype. METHODS AND
RESULTS: Between 2008 and 2012, VIRGO (Variation in Recovery: Role of Gender on
Outcomes of Young AMI Patients) prospectively enrolled acute myocardial
infarction patients aged 18 to 55 years in 103 hospitals at a 2:1 ratio of women
to men. Using an angiographically driven taxonomy, we defined patients as having
MI-CAD if there was revascularization or plaque >=50% and as having MINOCA if
there was <50% obstruction or a nonplaque mechanism. Patients who did not have an
angiogram or who received thrombolytics before an angiogram were excluded.
Outcomes included 1- and 12-month mortality and functional (Seattle Angina
Questionnaire [SAQ]) and psychosocial status. Of 2690 patients undergoing
angiography, 2374 (88.4%) had MI-CAD, 299 (11.1%) had MINOCA, and 17 (0.6%)
remained unclassified. Women had 5 times higher odds of having MINOCA than men
(14.9% versus 3.5%; odds ratio: 4.84; 95% confidence interval, 3.29-7.13). MINOCA
patients were more likely to be without traditional cardiac risk factors (8.7%
versus 1.3%; P<0.001) but more predisposed to hypercoaguable states than MI-CAD
patients (3.0% versus 1.3%; P=0.036). Women with MI-CAD were more likely than
those with MINOCA to be menopausal (55.2% versus 41.2%; P<0.001) or to have a
history of gestational diabetes mellitus (16.8% versus 11.0%; P=0.028). The
MINOCA mechanisms varied: a nonplaque mechanism was identified for 75 patients
(25.1%), and their clinical profiles and management also varied. One- and 12
month mortality with MINOCA and MI-CAD was similar (1-month: 1.1% and 1.7%
[P=0.43]; 12-month: 0.6% and 2.3% [P=0.68], respectively), as was adjusted 12
month SAQ quality of life (76.5 versus 73.5, respectively; P=0.06). CONCLUSIONS:
Young patients with MINOCA were more likely women, had a heterogeneous
mechanistic profile, and had clinical outcomes that were comparable to those of
MI-CAD patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
Unique identifier: NCT00597922.
PMID- 29954745
TI - Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): It's Time
to Face Reality!
PMID- 29954748
TI - Risk of Stroke or Death Is Associated With the Timing of Carotid Artery Stenting
for Symptomatic Carotid Stenosis: A Secondary Data Analysis of the German
Statutory Quality Assurance Database.
PMID- 29954747
TI - Metformin and Risk of Hypertension in Taiwanese Patients With Type 2 Diabetes
Mellitus.
AB - BACKGROUND: Whether metformin use may reduce hypertension risk has not been
studied. This study investigated such possibility in patients with type 2
diabetes mellitus. METHODS AND RESULTS: Newly diagnosed patients with type 2
diabetes mellitus during 1999-2005 were enrolled from the reimbursement database
of the Taiwan's National Health Insurance and followed to December 31, 2011.
Hypertension was defined either by a diagnosis or by a diagnosis plus the use of
angiotensin converting enzyme inhibitors/angiotensin receptor blockers and/or
calcium channel blockers. Analyses were conducted in a propensity score matched
pair cohort of 4810 ever users and 4810 never users. Cox proportional hazards
regression model was used to estimate the hazard ratios. Results showed that when
hypertension was defined by a diagnosis, 2261 never users and 1908 ever users
developed hypertension. The overall hazard ratio was 0.724 (0.681-0.769) and the
hazard ratios for the first (<2.0 months), second (2.0-13.0 months) and third
(>13.0 months) tertiles of cumulative duration were 0.820 (0.745-0.903), 0.692
(0.634-0.756), and 0.687 (0.630-0.749), respectively. When cumulative duration of
metformin therapy was treated as a continuous variable, the hazard ratio was
0.991 (0.989-0.994) for every 1-month increment of metformin use. When
hypertension was defined by a diagnosis plus the use of antihypertensive drugs,
the overall hazard ratio was 0.831 (0.771-0.895), the hazard ratios for the
respective tertiles were 0.868 (0.769-0.980), 0.852 (0.767-0.946), and 0.787
(0.709-0.874), and the hazard ratio was 0.994 (0.991-0.997) for every 1-month
increment of metformin use. CONCLUSIONS: A reduced risk of hypertension is
observed in metformin users in a dose-response pattern.
PMID- 29954746
TI - Imaging Cardiovascular Calcification.
PMID- 29954750
TI - Improved CNS exposure to tocilizumab after cerebrospinal fluid compared to
intravenous administration in rhesus macaques.
PMID- 29954749
TI - PPM1D-truncating mutations confer resistance to chemotherapy and sensitivity to
PPM1D inhibition in hematopoietic cells.
AB - Truncating mutations in the terminal exon of protein phosphatase Mg2+/Mn2+ 1D
(PPM1D) have been identified in clonal hematopoiesis and myeloid neoplasms, with
a striking enrichment in patients previously exposed to chemotherapy. In this
study, we demonstrate that truncating PPM1D mutations confer a chemoresistance
phenotype, resulting in the selective expansion of PPM1D-mutant hematopoietic
cells in the presence of chemotherapy in vitro and in vivo. Clustered regularly
interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9
nuclease mutational profiling of PPM1D in the presence of chemotherapy selected
for the same exon 6 mutations identified in patient samples. These exon 6
mutations encode for a truncated protein that displays elevated expression and
activity due to loss of a C-terminal degradation domain. Global phosphoproteomic
profiling revealed altered phosphorylation of target proteins in the presence of
the mutation, highlighting multiple pathways including the DNA damage response
(DDR). In the presence of chemotherapy, PPM1D-mutant cells have an abrogated DDR
resulting in altered cell cycle progression, decreased apoptosis, and reduced
mitochondrial priming. We demonstrate that treatment with an allosteric, small
molecule inhibitor of PPM1D reverts the phosphoproteomic, DDR, apoptotic, and
mitochondrial priming changes observed in PPM1D-mutant cells. Finally, we show
that the inhibitor preferentially kills PPM1D-mutant cells, sensitizes the cells
to chemotherapy, and reverses the chemoresistance phenotype. These results
provide an explanation for the enrichment of truncating PPM1D mutations in the
blood of patients exposed to chemotherapy and in therapy-related myeloid
neoplasms, and demonstrate that PPM1D can be a targeted in the prevention of
clonal expansion of PPM1D-mutant cells and the treatment of PPM1D-mutant disease.
PMID- 29954751
TI - CK1alpha and IRF4 are essential and independent effectors of immunomodulatory
drugs in primary effusion lymphoma.
AB - Primary effusion lymphoma (PEL) is an aggressive cancer with few treatment
options. The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide have
recently been shown to kill PEL cell lines, and lenalidomide is in clinical
trials against PEL. IMiDs bind to the CRL4CRBN E3 ubiquitin ligase complex,
leading to the acquisition of the Ikaros family zinc finger proteins 1 and 3
(IKZF1 and IKZF3), casein kinase 1 alpha (CK1alpha), and zinc finger protein 91
(ZFP91) as neosubstrates. IMiDs are effective against multiple myeloma because of
degradation of IKZF1 and IKZF3 and the consequent loss of interferon regulatory
factor 4 (IRF4) and MYC expression. Lenalidomide is also effective in chromosome
5q deletion-associated myelodysplastic syndrome as a result of degradation of
CK1alpha. An essential IKZF1-IRF4-MYC axis has recently been proposed to underlie
the toxicity of IMiDs in PEL. Here, we further investigate IMiD effectors in PEL
cell lines, based on genome-wide CRISPR/Cas9 screens for essential human genes.
These screens and extensive validation experiments show that, of the 4
neosubstrates, only CK1alpha is essential for the survival of PEL cell lines. In
contrast, IKZF1 and IKZF3 are dispensable, individually or in combination. IRF4
was critical in all 8 PEL cell lines tested, and surprisingly, IMiDs triggered
downregulation of IRF4 expression independently of both IKZF1 and IKZF3.
Reexpression of CK1alpha and/or IRF4 partially rescued PEL cell lines from IMiD
mediated toxicity. In conclusion, IMiD toxicity in PEL cell lines is independent
of IKZF1 and IKZF3 but proceeds through degradation of the neosubstrate CK1alpha
and downregulation of IRF4.
PMID- 29954752
TI - Brown Adipocyte-Specific PPARgamma (Peroxisome Proliferator-Activated Receptor
gamma) Deletion Impairs Perivascular Adipose Tissue Development and Enhances
Atherosclerosis in Mice.
AB - Objective- Perivascular adipose tissue (PVAT) contributes to vascular homeostasis
by producing paracrine factors. Previously, we reported that selective deletion
of PPARgamma (peroxisome proliferator-activated receptor gamma) in vascular
smooth muscle cells resulted in concurrent loss of PVAT and enhanced
atherosclerosis in mice. To address the causal relationship between loss of PVAT
and atherosclerosis, we used BA-PPARgamma-KO (brown adipocyte-specific PPARgamma
knockout) mice. Approach and Results- Deletion of PPARgamma in brown adipocytes
did not affect PPARgamma in white adipocytes or vascular smooth muscle cells or
PPARalpha and PPARdelta expression in brown adipocytes. However, development of
PVAT and interscapular brown adipose tissue was remarkably impaired, associated
with reduced expression of genes encoding lipogenic enzymes in the BA-PPARgamma
KO mice. Thermogenesis in brown adipose tissue was significantly impaired with
reduced expression of thermogenesis genes in brown adipose tissue and
compensatory increase in subcutaneous and gonadal white adipose tissues.
Remarkably, basal expression of inflammatory genes and macrophage infiltration in
PVAT and brown adipose tissue were significantly increased in the BA-PPARgamma-KO
mice. BA-PPARgamma-KO mice were crossbred with ApoE KO (apolipoprotein E
knockout) mice to investigate the development of atherosclerosis. Flow cytometry
analysis confirmed increased systemic and PVAT inflammation. Consequently,
atherosclerotic lesions were significantly increased in mice with impaired PVAT
development, thus indicating that the lack of normal PVAT is sufficient to drive
increased atherosclerosis. Conclusions- PPARgamma is required for functional PVAT
development. PPARgamma deficiency in PVAT, while still expressed in vascular
smooth muscle cell, enhances atherosclerosis and results in vascular and systemic
inflammation, providing new insights on the specific roles of PVAT in
atherosclerosis and cardiovascular disease at large.
PMID- 29954753
TI - Thoracic Aorta Calcification and Noncardiovascular Disease-Related Mortality.
AB - Objective- Arterial calcification is highly correlated with underlying
atherosclerosis. Arterial calcification of the thoracic aorta is evident in many
older individuals at high susceptibility to aging-related diseases and non
cardiovascular disease (CVD)-related mortality. In this study, we evaluated the
association of thoracic aorta calcification (TAC) with non-CVD morbidity and
mortality. Approach and Results- We analyzed data from participants in the Multi
Ethnic Study of Atherosclerosis, a prospective cohort study of subclinical
atherosclerosis, in which participants underwent cardiac computed tomography at
baseline and were followed longitudinally for incident CVD events and non-CVD
events. Using modified proportional hazards models accounting for the competing
risk of CVD death and controlling for demographics, CVD risk factors, coronary
artery calcium, and CVD events, we evaluated whether TAC was independently
associated with non-CVD morbidity and mortality. Among 6765 participants (mean
age, 62 years), 704 non-CVD deaths occurred for a median follow-up of 12.2 years.
Compared with no TAC, the highest tertile of TAC volume was associated with a
higher risk of non-CVD mortality (hazard ratio, 1.56; 95% confidence interval,
1.23-1.97), as well as several non-CVD diagnoses, including hip fracture (2.14;
1.03-4.46), chronic obstructive pulmonary disease (2.06; 1.29-3.29), and
pneumonia (1.79; 1.30-2.45), with magnitudes of association that were larger than
for those of coronary artery calcium. Conclusions- TAC is associated with non-CVD
morbidity and non-CVD mortality, potentially through a pathway that is unrelated
to atherosclerosis. TAC may be a general marker of biological aging and an
indicator of increased risk of non-CVD and death.
PMID- 29954754
TI - Cross-Sectional Associations Between Cardiac Biomarkers, Cognitive Performance,
and Structural Brain Changes Are Modified by Age.
AB - Objective- NT-proBNP (N-terminal pro-B-type natriuretic peptide) and cardiac
troponin T (cTNT) are associated with cognitive performance. Whether this extends
to individuals <60 years of age is unclear. We investigated whether age modified
the associations between NT-proBNP and cTNT and cognitive performance and
structural brain changes. Approach and Results- In 3011 individuals (60+/-8
years; 49% women), NT-proBNP and cTNT, memory, information processing speed and
executive functioning, grey matter (GM) and white matter, and white matter
hyperintensity (WMH) volumes were determined. We used regression, adjusted for
educational level, cardiovascular factors, and lifestyle factors, to test whether
cross-sectional associations between biomarkers and cognitive performance and
structural brain changes were modified by age (<60 versus >=60 years). >=60
years, higher NT-proBNP was associated with lower memory (beta [SD] per 10-fold
higher level [95% confidence interval (CI)], -0.11 [-0.22 to -0.00]), information
processing speed (-0.12 [95% CI, -0.21 to -0.03]), executive functioning (-0.12
[95% CI, -0.22 to -0.03]), and smaller GM (beta [mL] per 10-fold higher level,
6.89 [95% CI, -11.58 to -2.20]). Additionally, higher cTNT was associated with
lower memory (-0.33 [95% CI, -0.53 to -0.12]) and information processing speed (
0.17 [95% CI, -0.3 to -0.01]); with smaller GM (-16.07 [95% CI, -24.90 to -7.24])
and greater WMH (10beta WMH per 10-fold higher level, 0.31 [95% CI, 0.10-0.52]).
<60 years, NT-proBNP and cTNT were not associated with cognitive performance (
Pinteraction, <0.10). In contrast, higher NT-proBNP was associated with smaller
GM (-7.43 [95% CI, -11.70 to -3.16]) and greater WMH (0.13 [95% CI, 0.01-0.25];
Pinteraction,>0.10). Higher cTNT was associated with greater WMH (0.18 [95% CI,
0.01 to 0.37]; Pinteraction,>0.10) but not with GM (0.07 [95% CI, -6.87 to 7.02];
Pinteraction, <0.10). Conclusions- Biomarkers of cardiac injury are continuously
associated with structural brain changes in both older and younger individuals
but with poorer cognitive performance only in older individuals. These findings
stress the continuous nature of the heart-brain axis in the development of
cognitive impairment.
PMID- 29954756
TI - Seven days in medicine: 20-27 June 2018.
PMID- 29954755
TI - High-Density Lipoproteins and Apolipoprotein A-I Improve Stent Biocompatibility.
AB - Revascularization because of coronary artery disease is commonly achieved by
percutaneous coronary intervention with stent deployment. Refinement in
interventional techniques, major improvements in stent design (particularly drug
eluting stents), and adjunctive pharmacotherapy with dual antiplatelet regimens
have led to marked reductions in the overall rates of stent failure. However,
even with the advancements made in the latest generation of drug-eluting stents,
unresolved biological problems persist including delayed re-endothelialization
and neoatherosclerosis, which can promote late expansion of the neointima and
late stent thrombosis. Novel strategies are still needed beyond what is currently
available to specifically address the pathobiological processes that underpin the
residual risk for adverse clinical events. This review focuses on the emerging
evidence that HDL (high-density lipoproteins) and its main apo (apolipoprotein),
apoA-I, exhibit multiple vascular biological functions that are associated with
an improvement in stent biocompatibility. HDL/apoA-I have recently been shown to
inhibit in-stent restenosis in animal models of stenting and suppress smooth
muscle cell proliferation in in vitro studies. Reconstituted HDL also promotes
endothelial cell migration, endothelial progenitor cell mobilization, and re
endothelialization. Furthermore, reconstituted HDL decreases platelet activation
and HDL cholesterol is inversely associated with the risk of thrombosis. Finally,
reconstituted HDL/apoA-I suppresses key inflammatory mechanisms that initiate in
stent neoatherosclerosis and can efflux cholesterol from plaque macrophages, an
important function of HDLs that prevents plaque progression. These unique
multifunctional effects of HDL/apoA-I suggest that, if translated appropriately,
have the potential to improve stent biocompatibility. This may provide an
alternate and more efficacious therapeutic pathway for the translation of HDL.
PMID- 29954757
TI - Mass medicalisation is an iatrogenic catastrophe.
PMID- 29954758
TI - Breast Hormone Concentrations in Random Fine-Needle Aspirates of Healthy Women
Associate with Cytological Atypia and Gene Methylation.
AB - Sex steroid hormones contribute to breast cancer development, but data on
concentrations of these within breast tissue are limited. We performed
simultaneous multiparameter measurement of breast sex steroids, breast epithelial
cytology, and DNA methylation in 119 healthy women (54 pre- and 65
postmenopausal) without a history of breast cancer. Random fine-needle aspiration
(rFNA) of the breast was performed simultaneously with blood collection. Breast
samples were analyzed by LC/MS-MS for estrone, estradiol, progesterone,
androstenedione, and testosterone. Blood samples were assayed for estradiol and
progesterone by immunoassay. Cytomorphology was classified using the Masood
Score, and DNA methylation of eight genes was analyzed using quantitative
multiplexed methylation-specific PCR, and expressed as the cumulative methylation
index (CMI). Serum and breast concentrations of estradiol and progesterone showed
significant correlation (Spearman r = 0.34, Padj = 0.001 and r = 0.69, Padj <
0.0006, respectively). Progesterone concentration was significantly higher in the
premenopausal breast (Padj < 0.0008), and showed a luteal surge. Breast estrone
and estradiol concentrations did not differ significantly by menopause, but
androstenedione concentration was higher in the breasts of postmenopausal women
(P = 0.026 and Padj = 0.208). Breast androgens were significantly correlated with
breast density (Spearman r = 0.27, Padj = 0.02 for testosterone) and CMI
(Spearman r = 0.3, Padj = 0.038 for androstenedione). Our data indicate that
future larger studies of breast steroid hormones along with other parameters are
feasible. Significant associations of breast androgen concentrations with breast
density and gene methylation warrant future study. Cancer Prev Res; 11(9); 557
68. (c)2018 AACR.
PMID- 29954759
TI - Targeting Colon Luminal Lipid Peroxidation Limits Colon Carcinogenesis Associated
with Red Meat Consumption.
AB - Red meat is probably carcinogenic to humans (WHO/IARC class 2A), in part through
heme iron-induced lipoperoxidation. Here, we investigated whether red meat
promotes carcinogenesis in rodents and modulates associated biomarkers in
volunteers, speculating that an antioxidant marinade could suppress these effects
via limitation of the heme induced lipid peroxidation. We gave marinated or non
marinated beef with various degrees of cooking to azoxymethane-initiated rats,
Min mice, and human volunteers (crossover study). Mucin-depleted foci were scored
in rats, adenoma in Min mice. Biomarkers of lipoperoxidation were measured in the
feces and urine of rats, mice, and volunteers. The organoleptic properties of
marinated meat were tested. Fresh beef increased colon carcinogenesis and
lipoperoxidation in rats and mice and lipoperoxidation in humans. Without an
adverse organoleptic effect on meat, marinade normalized peroxidation biomarkers
in rat and mouse feces, reduced peroxidation in human feces and reduced the
number of Mucin-depleted foci in rats and adenoma in female Min mice. This could
lead to protective strategies to decrease the colorectal cancer burden associated
with red meat consumption. Cancer Prev Res; 11(9); 569-80. (c)2018 AACR.
PMID- 29954760
TI - Breast cancer metastasis to the bladder: a literature review.
AB - Given the prevalence of breast cancer and the mortality associated with
metastatic disease, it is imperative for physicians to not only be aware of
common sites but also of rare metastatic destinations such as the bladder. A
postmenopausal woman with a medical history of stage 2 invasive ductal carcinoma,
oestrogen receptor/progesterone receptor positive and human epidermal growth
factor receptor 2 negative, in remission for 9 years, presented to her primary
care physician with concerns of increased urinary urgency, frequency and
incontinence. The patient underwent cystoscopy with biopsy of an area of
granulation tissue. Biopsy revealed adenocarcinoma consistent with breast
primary. The common sites of metastases from breast cancer are lung, bone and
liver. This case is unique where breast cancer was found to metastasise to the
bladder. It is important for physicians to consider further investigation when a
breast cancer survivor develops urinary symptoms even without haematuria.
PMID- 29954761
TI - Disseminated histoplasmosis mimicking relapsed chronic lymphocytic leukaemia.
AB - Histoplasma microconidia when inhaled are presented in antigenic form to T cells,
limiting the extent of infection; however, defects in cellular immunity results
in disseminated disease. Chronic lymphocytic leukaemia (CLL) is a
lymphoproliferative disorder resulting in functionally impaired lymphocytes,
predisposing patients to various opportunistic infections. The author reports a
recently treated patient with CLL presenting with constitutional symptoms
accompanied by hepatosplenomegaly and diffuse adenopathy. Considering the recent
diagnosis and treatment of CLL, initial suspicion was relapsed disease. However,
considering the immune deficiency associated with CLL and its treatment,
infectious aetiologies were strongly considered. Further investigation revealed a
case of disseminated histoplasmosis mimicking CLL in this reported patient.
Considering appropriate diagnosis and timely therapy, the reported patient had
good prognosis despite being diagnosed with disseminated histoplasmosis. This
case highlights consideration of disseminated histoplasmosis in patients
presenting with diffuse adenopathy along with hepatomegaly and/or splenomegaly in
the right clinical setting.
PMID- 29954762
TI - Acute liver failure due to liver parenchymal infiltration with acute myelogenous
leukaemia in a patient with myelodysplastic syndrome.
AB - Liver involvement by acute leukaemia is rare and has a high mortality rate
despite treatment. We report a case of a 66-year-old woman undergoing treatment
for myelodysplastic syndrome with Vidaza (azacitidine) who presented with
abnormal liver function tests. Despite negative serologic testing and
unremarkable abdominal MRI, she continued to have significant elevation in
bilirubin and international normalised ratio and worsening mental status. Liver
biopsy was obtained and consistent with acute myelogenous leukaemia. The patient
had rapid demise due to acute liver failure and was unable to undergo treatment.
PMID- 29954763
TI - Post-transplant erythrocytosis refractory to ACE inhibitors and angiotensin
receptor blockers.
AB - Post-transplant erythrocytosis (PTE) is a condition with elevated haematocrit
(hct) in renal allograft recipients. The mainstay of treatment is ACE inhibitors
(ACEi) or angiotensin II receptor blockers (ARB), but seldom phlebotomy. PTE must
be recognised early to prevent major thromboembolic events. We present a case of
PTE that was refractory to blockade of renin-angiotensin system (RAS) by ACEi and
ARB and required phlebotomy for control of hct. Our review of medical literature
about prevalence and pathophysiology of PTE suggests that approximately 22% of
patients with PTE are refractory to ACEi/ARB treatment. There are four plausible
pathways that appear to play a role in causing PTE: disruption of erythropoietin
regulation, mitogenic effect of the RAS on erythroid lineage, insulin-like growth
factor 1 and androgenic stimulation. Presently, there is no unifying hypothesis
involving these factors, but refractoriness to ACEi/ARB may represent a distinct
subcategory of PTE.
PMID- 29954764
TI - Orbital blowout fracture from nose blowing.
AB - Orbital blowout fractures are nearly always caused by acute trauma. Non-traumatic
cases of orbital blowout fractures have only been rarely described. In this case
study, we discuss an orbital blowout fracture directly caused by nose blowing.
The patient developed unilateral eye swelling and orbital emphysema. It is
important for the clinician to investigate all suspected orbital blowout
fractures with imaging and full ophthalmological examination regardless of a
trauma history. Most cases of orbital emphysema resolve spontaneously, however
one must always exclude compression of the central retinal artery. This may
present as acute loss of vision and/or ophthalmoplegia.
PMID- 29954765
TI - Acute subclavian artery occlusion with associated clavicle fracture managed with
bypass graft alone.
AB - Subclavian artery injury is a rare consequence of clavicle fracture. It most
often results from penetrating trauma but can result from blunt trauma with
adjacent bone fragments causing rupture, pseudoaneurysm, dissection or thrombosis
of the artery. If flow through the subclavian artery is compromised there is a
risk of ipsilateral upper limb ischaemia. Life-threatening haemorrhage may result
in cases of laceration, and cerebral infarction may result from dissection.
Vascular injury in association with clavicle fracture is typically regarded as an
indication for internal fixation of the fracture. We present a case of subclavian
artery thrombosis in association with a comminuted midshaft clavicle fracture
causing limb ischaemia managed by carotid to brachial artery bypass without
internal fracture fixation. The fracture united at 4 weeks and there was no
sustained vascular or neurological impairment at follow-up. We advocate urgent
vascular intervention in subclavian artery injury. There is little discussion in
the literature regarding non-operative management of clavicle fractures with
subclavian artery injury. We suggest that select clavicle fractures with
subclavian artery injury can be safely managed non-operatively.
PMID- 29954766
TI - Early onset necrotising enterocolitis in association with congenital
diaphragmatic hernia in a term baby.
AB - We report a case of a male, term newborn with known left congenital diaphragmatic
hernia (CDH) who presented with circulatory compromise requiring maximal
inotropic support in the first 24 hours of life. Repeat X-ray at 24 hours showed
pneumatosis intestinalis. Emergency laparotomy was performed for suspected
necrotising enterocolitis. The terminal ileum to the sigmoid colon were frankly
necrotic with multiple perforations. Subtotal colectomy was performed. Although
the recovery was protracted, the baby had a favourable outcome with progressive
weight gain on follow-up at 3, 6 and 9 months of age.This case of CDH had a
postnatal systemic instability that was more severe than predicted, and as well
as assessing for persistent pulmonary hypertension of newborn should trigger
immediate suspicion for other organ involvement.
PMID- 29954767
TI - Regressive pyridoxine-induced sensory neuronopathy in a patient with
homocystinuria.
AB - Pyridoxine (vitamin B6) is an essential vitamin playing a crucial role in amino
acid metabolism. Pyridoxine is used for isoniazid side-effects prevention,
pyridoxine-dependent epilepsy treatment and cystathionine beta-synthase
deficiency (homocystinuria) treatment. However, vitamin B6 hypervitaminosis is
neurotoxic and may provoke a progressive sensory neuronopathy (sensory
ganglionopathy), usually when daily uptake is above 50 mg. We describe the case
of a 30-year-old patient with homocystinuria who was treated with pyridoxine 1250
1750 mg/day for 20 years and developed progressive sensory neuropathy with ataxia
and impaired sensation in the extremities. Electrodiagnostic testing demonstrated
non-length-dependent abnormalities of sensory nerve potentials, and sensory
ganglionopathy was diagnosed. Pyridoxine dosage was reduced to 500 mg/day,
resulting in the disappearance of sensory symptoms and ataxia, and the
normalisation of sensory nerve potentials. Our case indicates that pyridoxine
induced sensory ganglionopathy may be reversible, even after prolonged ingestion
of high doses of vitamin B6 for more than 20 years.
PMID- 29954768
TI - Large cell neuroendocrine carcinoma and adenocarcinoma of gallbladder with
concomitant hepatitis C infection.
AB - Neuroendocrinetumour (NET) of the gallbladder is an extremely rare tumour and
with coexisting adenocarcinoma an even rarer occurrence. Mixed NETs have the
tendency to invade the lymph nodes and the hepatic tissue from their high
malignant potential, leading to poor prognosis. Survival rates of the patients
with mixed NET can be improved with wide excision, adjuvant chemotherapy and
radiation. We present a case of 62-year-old woman with history of hepatitis C
infection, a risk factor for both hepatic and extrahepatic gastrointestinal
malignancies. Patient underwent exploratory laparotomy with resection of the
gallbladder and partial hepatectomy. Pathology showed high-grade larger cell
neuroendocrine carcinoma 5*4*3 cm along with two separate lesions found out to be
adenocarcinomas. In our patient, hepatitis C infection can be an inciting factor
for the development of these carcinomas. We will discuss the presentation,
treatment modalities and outcomes with this kind of coexisting tumours.
PMID- 29954769
TI - A case of oligodendroglioma and multiple sclerosis: Occam's razor or Hickam's
dictum?
AB - Tumefactive appearing lesions on brain imaging can cause a diagnostic dilemma. We
report a middle-aged man who presented with right-sided optic neuritis. A brain
MRI showed enhancement of the right optic nerve, and non-enhancing white matter
lesions including a 3 cm right frontal lesion with adjacent gyral expansion.
Cerebrospinal fluid analysis showed five oligoclonal bands not present in serum.
Glatiramer acetate was started for suspected tumefactive multiple sclerosis (MS).
A follow-up brain MRI 6 months later showed persistence of the frontal gyral
expansion. A brain biopsy led to the diagnosis of an oligodendroglioma,
isocitrate dehydrogenase-mutant and 1 p/19q co-deleted (WHO grade II), managed
with surgical resection and radiotherapy. Postoperative brain MRI showed a new
enhancing periventricular lesion, making the choice of optimal disease-modifying
therapy for MS challenging. This case highlights the possibility of coexistence
of MS and oligodendroglioma, and emphasises the importance of a tissue diagnosis
when atypical MS imaging features are present.
PMID- 29954770
TI - Acute COPD exacerbation presenting with pronounced intrabullous haemorrhage and
haemoptysis.
AB - A 54-year-old man with history of chronic obstructive pulmonary disease (COPD)
presented with subacute onset of chest pain, shortness of breath, productive
cough with haemoptysis and night sweats. There were no fever or recent weight
loss reported. The chest radiograph showed right upper lobe bullae with adjacent
opacification and an emphysematous lung. Due to worsening haemoptysis and
persistent chest pain, CT of the chest with contrast was performed, which
revealed moderate to severe emphysema and numerous blood-filled bullae. Cardiac
work-up for chest pain was negative for myocardial ischaemia and for aortic
dissection. Further infectious work-ups for mycobacterial and invasive fungal
infection were negative. The patient was treated for acute COPD exacerbation and
responded well to the antibiotics with the resolution of haemoptysis. Follow-up
CT of the chest revealed the gradual resolution of the haemorrhage, while the
patient remained asymptomatic.
PMID- 29954771
TI - Tip of the iceberg: congenital cataract with pre-existing posterior capsule
defect (PPCD): how vital is the role of ultrasound biomicroscopy?
PMID- 29954772
TI - Abdominal pain leading to incidental finding of polyarteritis nodosa.
PMID- 29954773
TI - Cavum vergae and psychiatric illness: substantive or serendipity?
PMID- 29954774
TI - Rare case of Gordon Holmes syndrome.
AB - Young-onset cerebellar syndromes are quite interesting and challenging for
treating clinicians. While dealing with such cases, a clinician should be aware
of rare possible causes too. We report a rare case of Gordon Holmes syndrome-an
autosomal recessive cerebellar ataxia with endocrinal abnormalities.
PMID- 29954775
TI - 'A snake and a crescent moon in a coronary angiogram'.
PMID- 29954776
TI - STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary
Non-Muscle-Invasive Bladder Cancer.
AB - Purpose: Most bladder cancers are early-stage tumors known as papillary non
muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs
recur locally, and up to 20% of these recurrences progress to muscle invasion.
There is an unmet need for additional biomarkers for stratifying tumors based on
their risk of recurrence and progression. We previously identified STAG2 as among
the most commonly mutated genes in NMIBC and provided initial evidence in a pilot
cohort that STAG2-mutant tumors recurred less frequently than STAG2 wild-type
tumors. Here, we report a STAG2 biomarker validation study using two independent
cohorts of clinically annotated papillary NMIBC tumors from the United States and
Europe.Experimental Design: The value of STAG2 immunostaining for prediction of
recurrence was initially evaluated in a cohort of 82 patients with papillary
NMIBC ("Georgetown cohort"). Next, the value of STAG2 immunostaining for
prediction of progression to muscle invasion was evaluated in a progressor
enriched cohort of 253 patients with papillary NMIBC ("Aarhus cohort").Results:
In the Georgetown cohort, 52% of NMIBC tumors with intact STAG2 expression
recurred, whereas 25% of STAG2-deficient tumors recurred (P = 0.02).
Multivariable analysis identified intact STAG2 expression as an independent
predictor of recurrence (HR = 2.4; P = 0.05). In the progressor-enriched Aarhus
cohort, 38% of tumors with intact STAG2 expression progressed within 5 years,
versus 16% of STAG2-deficient tumors (P < 0.01). Multivariable analysis
identified intact STAG2 expression as an independent predictor of progression (HR
= 1.86; P = 0.05).Conclusions: STAG2 IHC is a simple, binary, new assay for risk
stratification in papillary NMIBC. Clin Cancer Res; 24(17); 4145-53. (c)2018
AACR.
PMID- 29954778
TI - Fill in the Gaps: An Unresponsive 55-Year-Old Man.
PMID- 29954777
TI - Molecular Profiling of Patients with Pancreatic Cancer: Initial Results from the
Know Your Tumor Initiative.
AB - Purpose: To broaden access to and implementation of precision medicine in the
care of patients with pancreatic cancer, the Know Your Tumor (KYT) program was
initiated using a turn-key precision medicine system. Patients undergo
commercially available multiomic profiling to determine molecularly rationalized
clinical trials and off-label therapies.Experimental Design: Tumor samples were
obtained for 640 patients from 287 academic and community practices covering 44
states. College of American Pathologists/Clinical Laboratory Improvement
Amendments-accredited laboratories were used for genomic, proteomic, and
phosphoprotein-based molecular profiling.Results: Tumor samples were adequate for
next-generation sequencing in 96% and IHC in 91% of patients. A tumor board
reviewed the results for every patient and found actionable genomic alterations
in 50% of patients (with 27% highly actionable) and actionable proteomic
alterations (excluding chemopredictive markers) in 5%. Actionable alterations
commonly found were in DNA repair genes (BRCA1/2 or ATM mutations, 8.4%) and cell
cycle genes (CCND1/2/3 or CDK4/6 alterations, 8.1%). A subset of samples was
assessed for actionable phosphoprotein markers. Among patients with highly
actionable biomarkers, those who received matched therapy (n = 17) had a
significantly longer median progression-free survival (PFS) than those who
received unmatched therapy [n = 18; PFS = 4.1 vs. 1.9 months; HR, 0.47; 95%
confidence interval (CI): 0.24-0.94; P adj = 0.03].Conclusions: A comprehensive
precision medicine system can be implemented in community and academic settings,
with highly actionable findings observed in over 25% of pancreatic cancers.
Patients whose tumors have highly actionable alterations and receive matched
therapy demonstrated significantly increased PFS. Our findings support further
prospective evaluation of precision oncology in pancreatic cancer. Clin Cancer
Res; 24(20); 5018-27. (c)2018 AACR.
PMID- 29954779
TI - Commentary.
PMID- 29954780
TI - Commentary.
PMID- 29954781
TI - Negative Anion Gap in a Teenager with Epilepsy.
PMID- 29954782
TI - Nicotiana tabacum, or the Letter "Aleph" with 22 Flowers.
PMID- 29954783
TI - Prevalence and clinical consequences of cytomegalovirus DNA in the aqueous humour
and corneal transplants.
AB - AIM: To determine the prevalence and clinical consequences of cytomegalovirus
(CMV) DNA in the aqueous and corneal tissues obtained at the time of corneal
transplantation to evaluate the diagnostic value of PCR analysis in identifying
patients at risk of postkeratoplasty CMV endotheliitis. METHODS: Thirty patients
who underwent corneal transplantation were included in 2011. The aqueous, excised
recipient corneas and donor corneoscleral rims were analysed by PCR for the
presence of CMV DNA. The medical records of the patients were retrospectively
reviewed and linked with PCR results. RESULTS: CMV DNA was detected in three
(10%) aqueous, eight (26.7%) recipient corneas and six (20.0%) donor corneas
obtained during keratoplasty from the 30 patients. Postoperatively, four
patients, who had CMV DNA in either aqueous (3) or recipient cornea (1), were
diagnosed with CMV endotheliitis based on clinical features and repeat aqueous
tapping for real-time PCR analysis. At the median 60.5 months follow-up, 8
(72.7%), including 4 with postkeratoplasty CMV endotheliitis, of the 11 patients
with CMV positivity in any one sample had graft failure, while 9 (47.3%) of the
19 patients without evidence of CMV DNA experienced graft failure. CONCLUSIONS:
We found a relatively high prevalence of CMV DNA in the aqueous and corneas
obtained during keratoplasty. All the patients who had CMV positivity in aqueous
developed CMV endotheliitis postoperatively and experienced graft failure
eventually. Aqueous tapping at the time of corneal transplantation for PCR
analysis may help to improve the diagnosis and follow-up management of
postkeratoplasty CMV endotheliitis.
PMID- 29954784
TI - Squamous cell carcinoma in the anophthalmic socket: a series of four cases with
HPV-16 profiling.
AB - PURPOSE: To present the clinical and histological features of squamous cell
carcinoma (SCC) in the anophthalmic socket in four adult patients, and to
determine the presence of human papillomavirus infection (HPV). METHODS:
Retrospective case series of four adult patients with SCC of the anophthalmic
socket. P16 immunohistochemistry and HPV testing was carried out in all cases.
The authors report clinical findings, histopathology, management and outcomes for
all four patients with conjunctival SCC. Previously reported cases of
conjunctival SCC in anophthalmic sockets were reviewed. RESULTS: Four adult
patients presented with eyelid lumps, discharge or change in prosthesis fit.
Common examination findings included papillomatous changes, eyelid masses and
epithelial changes. Three out of the four cases (75%) were positive for p16 by
immunohistochemistry and the same cases positive for HPV-16 DNA. All patients
received cryotherapy, topical or intralesional chemotherapy. Two patients
proceeded to exenteration for control of invasive disease. CONCLUSIONS: To the
authors' knowledge, this is the largest series of SCC in the anophthalmic socket
with comprehensive annotation of HPV status. Although socket conjunctiva is
protected from environmental radiation, there is still a risk of neoplastic
transformation in this tissue, thus patient education and regular checking of
sockets by ophthalmologists should be undertaken as a preventative measure. The
potential role of HPV in these tumours warrants further investigation.
PMID- 29954785
TI - Quantitative retinal microvasculature in children using swept-source optical
coherence tomography: the Hong Kong Children Eye Study.
AB - AIMS: To evaluate the distributions of quantitative optical coherence tomography
angiography (OCT-A) metrics and its associated factors in children. METHODS: 1059
children aged 6-8 years were recruited from the Hong Kong Children Eye Study. All
the participants underwent OCT-A with a swept-source OCT. Retinal
microvasculature on superficial capillary plexus was assessed and quantified by a
customised automated image analysis programme. Univariable and multiple linear
regression analyses were performed to determine systemic (body mass index (BMI),
waist circumference, head circumference and blood pressure), demographic and
ocular (axial length (AL), macular thickness and volume, retinal nerve fibre
layer (RNFL) thickness and visual acuity) variables (independent variables)
associated with OCT-A metrics (dependent variables). RESULTS: In multiple linear
regression analyses, enlarged foveal avascular zone area was associated with
female gender (beta=0.110, p<0.001), decreased AL (beta=-0.097, p<0.001) and
decreased central macular thickness (beta=-0.008, p<0.001). Decreased vessel
density was associated with increased BMI (beta=-4.12*10-4, p=0.006), decreased
AL (beta=0.003, p<0.001) and decreased central macular thickness (beta=7.87*10-5,
p=0.001). Increased vessel diameter index was associated with female gender
(beta=0.020, p=0.007) and decreased AL (beta=-0.020, p<0.001). Decreased fractal
dimension was associated with older age (beta=-0.001, p=0.008). There were no
significant correlations between OCT-A metrics with visual acuity, RNFL
thickness, central corneal thickness, waist circumference, head circumference and
blood pressure (all p>0.05). CONCLUSION: Our findings provides new information on
baseline morphology of retinal microvasculature and its associated factors in
school children, which will be useful for interpreting OCT-A metrics and for
identifying and characterising pathological changes in retinal microvasculature.
PMID- 29954787
TI - Happy Birthday NHS.
PMID- 29954786
TI - Prior non-irradiative focal therapies do not compromise the efficacy of delayed
episcleral plaque brachytherapy in retinoblastoma.
AB - BACKGROUND/AIMS: Non-irradiative local therapies have shown promise in delaying
or supplanting external beam radiotherapy (EBRT) and enucleation in patients with
retinoblastoma. We hypothesised that prior focal therapy does not compromise the
efficacy of delayed episcleral plaque brachytherapy (epBRT). METHODS: We
performed an institutional review board-approved medical record review of
patients with retinoblastoma who were treated with I-125 epBRT prior to (primary)
or following chemoreduction (delayed), alone and in combination with non
irradiative focal therapy. Clinical and treatment characteristics were retrieved.
Treatment failure was defined as the need for subsequent EBRT and/or enucleation.
Event-free and ocular survival rates were calculated from the date of plaque
placement. The cumulative incidences (CIs) of treatment failure and enucleation
were compared across strata using Gray's test. RESULTS: We identified 50 patients
with retinoblastoma (54 eyes), who received a total of 56 plaques between January
1986 and December 2010, with a median follow-up of 8.3 years (range, 0.8-21.2
years). The median time from diagnosis to plaque placement was 12.7 months
(range, 0.1-128 months). The CI and 95% CI of treatment failure and enucleation
following epBRT at 5 years was 37%+/-7.2% and42.2%+/-7.3%, respectively. The lack
of prior diode or green laser therapy was predictive of increased risk for
treatment failure (p=0.02 and 0.03). International Classification group C or D
was predictive of decreased time to enucleation (p=0.004). The use of any focal
therapy was not predictive of time to treatment failure (p=0.33). CONCLUSIONS:
The use of non-irradiative focal therapies prior to or following epBRT does not
decrease the time to enucleation or treatment failure.
PMID- 29954788
TI - General practice at the heart of the NHS: now and in the future.
PMID- 29954789
TI - Physician associates in general practice: what is their role?
PMID- 29954790
TI - The future of nursing in primary care.
PMID- 29954791
TI - Quality after the QOF? Before dismantling it, we need a redefined measure of
'quality'.
PMID- 29954792
TI - Written reflection in NHS appraisal: time for an alternative.
PMID- 29954793
TI - Creating a holistic support service for people with vision impairment.
PMID- 29954794
TI - Clinical pharmacists in general practice.
PMID- 29954795
TI - Long-term conditions and the National Diabetes Audit.
PMID- 29954796
TI - Discontinuity of care: is it undermining our response to domestic violence and
abuse?
PMID- 29954797
TI - Diagnosing violence.
PMID- 29954798
TI - Feeling blue, sad, or depressed: how to manage these patients.
PMID- 29954799
TI - Books: Lost Connections: Uncovering the Real Causes of Depression - and the
Unexpected Solutions: Searching for Depression Treatments.
PMID- 29954800
TI - Bad Medicine: The NHS at 70.
PMID- 29954801
TI - The Bromley by Bow Centre: harnessing the power of community.
PMID- 29954802
TI - Using CPRD data for public health research.
PMID- 29954803
TI - Yonder: Doctor emigration, vitiligo, canes, and self-harm pictures on Instagram.
PMID- 29954804
TI - Ten years of MRCGP International South Asia: a beacon of excellence.
PMID- 29954805
TI - Books: With the End in Mind: Dying, Death and Wisdom in an Age of Denial: The
Value of Palliative Care.
PMID- 29954806
TI - Books: Measuring Research: What Everyone Needs to Know: Anyone For Donuts?
PMID- 29954807
TI - Books: If You Want Good Personal Healthcare - See a Vet. Industrialised Humanity:
Why and How We Should Care for One Another? Bringing Humanity Back.
PMID- 29954808
TI - Books: Eleanor Oliphant is Completely Fine: Meaningful Contact.
PMID- 29954809
TI - #GPToo.
PMID- 29954810
TI - The future of the NHS and general practice.
PMID- 29954811
TI - Identifying and treating older patients with malnutrition in primary care: the
MUST screening tool.
PMID- 29954812
TI - Diagnosis and management of spondyloarthritis in the over-16s: NICE guideline.
PMID- 29954813
TI - Alternative drug to prevent postpartum bleeding could save many lives in low
income countries.
PMID- 29954814
TI - Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in
advanced acute lymphoblastic leukemia.
AB - In the phase 3 TOWER study, blinatumomab demonstrated an overall survival benefit
over standard-of-care chemotherapy (SOC) in adults with relapsed or refractory
(r/r) Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic
leukemia (ALL). Nearly all patients in both treatment arms experienced an adverse
event (AE), and the incidence rate of serious AEs was higher for blinatumomab.
However, as treatment exposure differed between the 2 arms, we conducted an
exploratory safety analysis comparing exposure-adjusted event rates (EAERs) of
blinatumomab vs SOC. Analyses were conducted for all patients who received
therapy (safety population). Patients received a median (range) of 2 cycles (1-9)
of blinatumomab (N = 267) vs 1 cycle (1-4) of SOC (N = 109). Grade >=3 AE rates
were generally higher in cycle 1 of blinatumomab than in cycle 2 (76% vs 37%).
After adjusting for time on treatment, EAERs of grade >=3 were significantly
lower for blinatumomab vs SOC overall (10.73 vs 45.27 events per patient-year; P
< .001) and for events of clinical interest, including infections (1.63 vs 6.49
events per patient-year; P < .001), cytopenias (3.64 vs 20.07 events per patient
year; P < .001), and neurologic events (0.38 vs 0.95 events per patient-year; P =
.008). The EAER of grade >=3 cytokine-release syndrome was higher for
blinatumomab than for SOC (0.16 vs 0 events per patient-year; P = .038). These
data further support the role of blinatumomab as an efficacious and well
tolerated treatment option for patients with r/r Ph- ALL. This trial was
registered at www.clinicaltrials.gov as #NCT02013167.
PMID- 29954815
TI - Assessing Corticospinal Tract Asymmetry in Unilateral Polymicrogyria.
AB - BACKGROUND AND PURPOSE: Asymmetry of the corticospinal tract in congenital
lesions is a good prognostic marker for preserved motor function after
hemispherectomy. This study aimed to assess this marker and provide a clinically
feasible approach in selected cases of unilateral polymicrogyria. MATERIALS AND
METHODS: Corticospinal tract asymmetry of 9 patients with unilateral
polymicrogyria substantially affecting the central region was retrospectively
assessed on axial T1WI and DTI. Volumes of the brain stem and thalamus and DTI
parameters of the internal capsule were measured. Two neuroradiologists
independently rated the right-left asymmetry at 4 levels along the corticospinal
tract. DTI tractography was used to determine the motor cortex within
polymicrogyria, with task-based functional MR imaging available in 3/9 cases.
RESULTS: Visual assessment of the brain stem asymmetry showed excellent
correlation with quantitative measures on both T1WI and color-coded DTI maps (P =
.007 and P = .023). Interrater reliability regarding structural and DTI-based
corticospinal tract asymmetry was best at the midbrain (Cohen kappa = 0.77, P =
.018). Three patients underwent functional hemispherectomy with postsurgical
stable motor function, all showing marked corticospinal tract asymmetry
preoperatively. Following the DTI-based corticospinal tract trajectories allowed
identifying the presumed primary motor region within the dysplastic cortex in 9/9
patients, confirmed by functional MR imaging in 3/3 cases. CONCLUSIONS: Visual
assessment of corticospinal tract asymmetry in unilateral polymicrogyria
involving the motor cortex is most reliable with T1WI and color-coded DTI maps at
the level of the midbrain. Pronounced asymmetry predicts preserved motor function
after hemispherectomy. DTI-based tractography can be used as a guidance tool to
the motor cortex within polymicrogyria.
PMID- 29954817
TI - Prognostic Value of the Metabolic and Volumetric Parameters of 11C-Methionine
Positron-Emission Tomography for Gliomas: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Several studies have demonstrated that 11C-methionine positron
emission tomography provides information on prognosis. PURPOSE: We performed a
systematic review and meta-analysis of the prognostic value of the metabolic and
volumetric parameters of 11C-methionine-PET for gliomas. DATA SOURCES: A
systematic search was performed using the following combination of keywords:
"methionine," "PET," "glioma," and "prognosis." STUDY SELECTION: The inclusion
criteria were the use of 11C-methionine-PET as an imaging tool, studies limited
to gliomas, studies including metabolic parameters (tumor-to-normal ratio) and/or
volumetric parameters (metabolic tumor volume), and studies reporting survival
data. The electronic search first identified 181 records, and 14 studies were
selected. DATA ANALYSIS: Event-free survival and overall survival were the
outcome measures of interest. The effect of the tumor-to-normal ratio and
metabolic tumor volume on survival was determined by the effect size of the
hazard ratio. Hazard ratios were extracted directly from each study when provided
or determined by analyzing the Kaplan-Meier curves. DATA SYNTHESIS: The combined
hazard ratios of the tumor-to-normal ratio for event-free survival was 1.74 with
no significance and that of the tumor-to-normal ratio for overall survival was
2.02 with significance. The combined hazard ratio of the metabolic tumor volume
for event-free survival was 2.72 with significance and that of the metabolic
tumor volume for overall survival was 3.50 with significance. LIMITATIONS: The
studies selected were all retrospective, and there were only 4 studies involving
the metabolic tumor volume. CONCLUSIONS: The present meta-analysis of 11C
methionine-PET suggests that the tumor-to-normal ratio for overall survival and
the metabolic tumor volume for event-free survival and overall survival are
significant prognostic factors for patients with gliomas.
PMID- 29954818
TI - Puzzling pieces of chromosome 7 loss or deletion.
PMID- 29954816
TI - Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate
Idiopathic Parkinson Disease.
AB - BACKGROUND AND PURPOSE: Several new MR imaging techniques have shown promising
results in patients with Parkinson disease; however, the comparative diagnostic
values of these measures at the individual level remain unclear. Our aim was to
compare the diagnostic value of MR imaging biomarkers of substantia nigra damage
for distinguishing patients with Parkinson disease from healthy volunteers.
MATERIALS AND METHODS: Thirty-six patients and 20 healthy volunteers were
prospectively included. The MR imaging protocol at 3T included 3D T2-weighted and
T1-weighted neuromelanin-sensitive images, diffusion tensor images, and R2*
mapping. T2* high-resolution images were also acquired at 7T to evaluate the
dorsal nigral hyperintensity sign. Quantitative analysis was performed using ROIs
in the substantia nigra drawn manually around the area of high signal intensity
on neuromelanin-sensitive images and T2-weighted images. Visual analysis of the
substantia nigra neuromelanin-sensitive signal intensity and the dorsolateral
nigral hyperintensity on T2* images was performed. RESULTS: There was a
significant decrease in the neuromelanin-sensitive volume and signal intensity in
patients with Parkinson disease. There was also a significant decrease in
fractional anisotropy and an increase in mean, axial, and radial diffusivity in
the neuromelanin-sensitive substantia nigra at 3T and a decrease in substantia
nigra volume on T2* images. The combination of substantia nigra volume, signal
intensity, and fractional anisotropy in the neuromelanin-sensitive substantia
nigra allowed excellent diagnostic accuracy (0.93). Visual assessment of both
substantia nigra dorsolateral hyperintensity and neuromelanin-sensitive images
had good diagnostic accuracy (0.91 and 0.86, respectively). CONCLUSIONS: The
combination of neuromelanin signal and volume changes with fractional anisotropy
measurements in the substantia nigra showed excellent diagnostic accuracy.
Moreover, the high diagnostic accuracy of visual assessment of substantia nigra
changes using dorsolateral hyperintensity analysis or neuromelanin-sensitive
signal changes indicates that these techniques are promising for clinical
practice.
PMID- 29954820
TI - The microbiome: more than a gut reaction.
PMID- 29954819
TI - Lipid metabolism in terminal erythropoiesis.
PMID- 29954821
TI - "Double-expressor" intravascular large B-cell lymphoma involving the female
genital tract.
PMID- 29954822
TI - Cryoglobulin-induced red blood cell morphologic changes.
PMID- 29954823
TI - Arruda VR, Doshi BS, Samelson-Jones BJ. Novel approaches to hemophilia therapy:
successes and challenges. Blood. 2017;130(21):2251-2256.
PMID- 29954824
TI - 12 Tips to Nephrology Teams Supporting Patients with Advanced Kidney Disease: An
Advocate's Dozen.
PMID- 29954825
TI - Protein Energy Wasting in Hemodialysis Patients.
PMID- 29954826
TI - Emotional Impact of Illness and Care on Patients with Advanced Kidney Disease.
AB - BACKGROUND AND OBJECTIVES: The highly specialized and technologically focused
approach to care inherent to many health systems can adversely affect patients'
emotional experiences of illness, while also obscuring these effects from the
clinician's view. We describe what we learned from patients with advanced kidney
disease about the emotional impact of illness and care. DESIGN, SETTING,
PARTICIPANTS, & MEASUREMENTS: As part of an ongoing study on advance care
planning, we conducted semistructured interviews at the VA Puget Sound Healthcare
System in Seattle, Washington, with 27 patients with advanced kidney disease
between April of 2014 and May of 2016. Of these, ten (37%) were receiving center
hemodialysis, five (19%) were receiving peritoneal dialysis, and 12 (44%) had an
eGFR<=20 ml/min per 1.73 m2 and had not started dialysis. Interviews were
audiotaped, transcribed, and analyzed inductively using grounded theory methods.
RESULTS: We here describe three emergent themes related to patients' emotional
experiences of care and illness: (1) emotional impact of interactions with
individual providers: when providers seemed to lack insight into the patient's
experience of illness and treatment, this could engender a sense of mistrust,
abandonment, isolation, and/or alienation; (2) emotional impact of encounters
with the health care system: just as they could be affected emotionally by
interactions with individual providers, patients could also be affected by how
care was organized, which could similarly lead to feelings of mistrust,
abandonment, isolation, and/or alienation; and (3) emotional impact of meaning
making: patients struggled to make sense of their illness experience, worked to
apportion blame, and were often quick to blame themselves and to assume that
their illness could have been prevented. CONCLUSIONS: Interactions with
individual providers and with the wider health system coupled with patients' own
struggles to make meaning of their illness can take a large emotional toll. A
deeper appreciation of patients' emotional experiences may offer important
opportunities to improve care.
PMID- 29954827
TI - Peak ACL force during jump landing in downhill skiing is less sensitive to
landing height than landing position.
AB - BACKGROUND: Competitive skiers face a high risk of sustaining an ACL injury
during jump landing in downhill skiing. There is a lack of knowledge on how
landing height affects this risk. OBJECTIVES: To evaluate the effect of varied
landing height on peak ACL force during jump landing and to compare the effect of
the landing height with the effect of the landing position varied by the trunk
lean of the skier. METHODS: A 25-degree-of-freedom sagittal plane musculoskeletal
model of an alpine skier, accompanied by a dynamic optimisation framework, was
used to simulate jump landing manoeuvres in downhill skiing. First, a reference
simulation was computed tracking experimental data of competitive downhill skier
performing a jump landing manoeuvre. Second, sensitivity studies were performed
computing 441 landing manoeuvres with perturbed landing height and trunk lean of
the skier, and the corresponding effects on peak ACL force were determined.
RESULTS: The sensitivity studies revealed that peak ACL force increased with jump
height and backward lean of the skier as expected. However, peak ACL was about
eight times more sensitive to the trunk lean of the skier compared with landing
height. The decreased sensitivity of the landing height was based on the lower
effects on the knee muscle forces and the shear component of the knee joint
reaction force. CONCLUSION: Preventive measures are suggested to focus primarily
on avoiding trunk backward lean of the skier, and consequently on proper jump
preparation and technique, and secondarily on strategies to reduce landing height
during jumps.
PMID- 29954828
TI - Comparative effectiveness of treatment options for plantar heel pain: a
systematic review with network meta-analysis.
AB - OBJECTIVE: To evaluate the comparative effectiveness of current treatment options
for plantar heel pain (PHP). DESIGN: Systematic review and network meta-analysis
(NMA). DATA SOURCES: Medline, EMBASE, CINAHL, AMED, PEDro, Cochrane Database, Web
of Science and WHO Clinical Trials Platform were searched from their inception
until January 2018. STUDY SELECTION: Randomised controlled trials (RCTs) of
adults with PHP investigating common treatments (ie, corticosteroid injection,
non-steroidal anti-inflammatory drugs, therapeutic exercise, orthoses and/or
extracorporeal shockwave therapy (ESWT)) compared with each other or a no
treatment, placebo/sham control. DATA EXTRACTION AND ANALYSIS: Data were
extracted and checked for accuracy and completeness by pairs of reviewers.
Primary outcomes were pain and function. Comparative treatment effects were
analysed by random effects NMA in the short term, medium term and long term.
Relative ranking of treatments was assessed by surface under the cumulative
ranking probabilities (0-100 scale). RESULTS: Thirty-one RCTs (total n=2450
patients) were included. There was no evidence of inconsistency detected between
direct and indirect treatment comparisons in the networks, but sparse data led to
frequently wide CIs. Available evidence does not suggest that any of the commonly
used treatments for the management of PHP are better than any other, although
corticosteroid injections, alone or in combination with exercise, and ESWT were
ranked most likely to be effective for the management of short-term, medium-term
and long-term pain or function; placebo/sham/control appeared least likely to be
effective; and exercise appeared to only be beneficial for long-term pain or
function. CONCLUSIONS: Current evidence is equivocal regarding which treatment is
the most effective for the management of PHP. Given limited understanding of long
term effects, there is need for large, methodologically robust multicentre RCTs
investigating and directly comparing commonly used treatments for the management
of PHP. PROSPERO REGISTRATION NUMBER: CRD42016046963.
PMID- 29954829
TI - Src activation by Chk1 promotes actin patch formation and prevents chromatin
bridge breakage in cytokinesis.
AB - In cytokinesis with chromatin bridges, cells delay abscission and retain actin
patches at the intercellular canal to prevent chromosome breakage. In this study,
we show that inhibition of Src, a protein-tyrosine kinase that regulates actin
dynamics, or Chk1 kinase correlates with chromatin breakage and impaired
formation of actin patches but not with abscission in the presence of chromatin
bridges. Chk1 is required for optimal localization and complete activation of
Src. Furthermore, Chk1 phosphorylates human Src at serine 51, and phosphorylated
Src localizes to actin patches, the cell membrane, or the nucleus.
Nonphosphorylatable mutation of S51 to alanine reduces Src catalytic activity and
impairs formation of actin patches, whereas expression of a phosphomimicking Src
S51D protein rescues actin patches and prevents chromatin breakage in Chk1
deficient cells. We propose that Chk1 phosphorylates Src-S51 to fully induce Src
kinase activity and that phosphorylated Src promotes formation of actin patches
and stabilizes chromatin bridges. These results identify proteins that regulate
formation of actin patches in cytokinesis.
PMID- 29954830
TI - The Calcium-Dependent Protease Calpain-1 Links TRPC6 Activity to Podocyte Injury.
AB - BACKGROUND: The hallmark of podocytopathies, such as FSGS, is podocyte injury
resulting in proteinuria. Transient receptor potential channel C6 (TRPC6) is a
calcium-conducting ion channel expressed at the slit diaphragm. TRPC6 gain-of
function mutations and glomerular TRPC6 overexpression are associated with
proteinuria. However, the pathways linking TRPC6 to podocyte injury, which is
characterized by loss of the slit diaphragm protein nephrin, activation of
several intracellular pathways (including calcineurin-NFAT signaling), and
cytoskeletal rearrangement, remain elusive. METHODS: We tested whether the
calcium-dependent protease calpain-1 mediates TRPC6-dependent podocyte injury in
human and experimental FSGS and cultured podocytes. RESULTS: Compared with
kidneys of healthy controls, kidneys of patients with FSGS had increased TRPC6
expression, increased calpain and calcineurin activity, and reduced expression of
the calpain target Talin-1, which links the actin cytoskeleton to integrins and
is critical for podocyte cytoskeletal stability. In a rat model of human FSGS,
increased glomerular and urinary calpain activity associated with reduced Talin-1
abundance, enhanced calcineurin activity, and increased proteinuria. Treatment
with the calpain inhibitor calpeptin prevented these effects. In cultured
podocytes, pharmacologic stimulation of TRPC6-dependent calcium influx increased
calpain-1 and calcineurin activity and reduced Talin-1 expression, and knockdown
of TRPC6 or calpain-1 prevented these effects. CONCLUSIONS: We elucidated a novel
mechanism that links TRPC6 activity to calpain-1 activation and through Talin-1
loss and possibly, calcineurin activation, the podocyte injury characterizing
FSGS. Therefore, calpain-1 and/or TRPC6 inhibition could be future therapeutic
options to treat patients with FSGS or other podocytopathies.
PMID- 29954831
TI - TECH Parenting to Promote Effective Media Management.
PMID- 29954832
TI - Uropathogen Resistance and Antibiotic Prophylaxis: A Meta-analysis.
AB - CONTEXT: Limited data exist regarding uropathogen resistance in randomized
controlled trials of urinary tract infection (UTI) prevention and antibiotic
prophylaxis. OBJECTIVE: To assess the effect of prophylaxis on developing a
multidrug-resistant first recurrent UTI among children with vesicoureteral
reflux. DATA SOURCES: Cochrane Kidney and Transplant Specialized Register through
May 25, 2017. STUDY SELECTION: Randomized controlled trials of patients <=18
years of age with a history of vesicoureteral reflux being treated with
continuous antibiotic prophylaxis compared with no treatment or placebo with
available antibiotic sensitivity profiles. DATA EXTRACTION: Two independent
observers abstracted data and assessed quality and validity per Preferred
Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Adjusted
meta-analyses were performed by using a mixed-effects logistic regression model.
RESULTS: One thousand two hundred and ninety-nine patients contributed 224 UTIs.
Patients treated with prophylaxis were more likely to have a multidrug-resistant
infection (33% vs 6%, P < .001) and were more likely to receive broad-spectrum
antibiotics (68% vs 49%, P = .004). Those receiving prophylaxis had 6.4 times the
odds (95% confidence interval: 2.7-15.6) of developing a multidrug-resistant
infection. One multidrug-resistant infection would develop for every 21 reflux
patients treated with prophylaxis. LIMITATIONS: Variables that may contribute to
resistance such as medication adherence and antibiotic exposure for other
illnesses could not be evaluated. CONCLUSIONS: Prophylaxis increases the risk of
multidrug resistance among recurrent infections. This has important implications
in the risk-benefit assessment of prophylaxis as a management strategy and in the
selection of empirical treatment of breakthrough infections in prophylaxis
patients.
PMID- 29954834
TI - UMATracker: an intuitive image-based tracking platform.
AB - Image-based tracking software are regarded as valuable tools in collective animal
behaviour studies. For such operations, image preprocessing is a prerequisite,
and the users are required to build an appropriate image-processing pipeline for
extracting the shape of animals. Even if the users successfully design an image
processing pipeline, unexpected noise in the video frame may significantly reduce
the tracking accuracy in the tracking step. To address these issues, we propose
UMATracker (Useful Multiple Animal Tracker), which supports flexible image
preprocessing by visual programming, multiple tracking algorithms and a manual
tracking error-correction system. UMATracker employs a visual programming user
interface, wherein the user can intuitively design an image-processing pipeline.
Moreover, the software also enables the user to visualize the effect of image
processing. We implement four different tracking algorithms to enable the users
to choose the most suitable algorithm. In addition, UMATracker provides a manual
correction tool for identifying and correcting tracking errors.
PMID- 29954835
TI - Weakly electric fish distinguish between envelope stimuli arising from different
behavioral contexts.
AB - Understanding how sensory information is processed by the brain in order to give
rise to behavior remains poorly understood in general. Here, we investigated the
behavioral responses of the weakly electric fish Apteronotus albifrons to stimuli
arising from different contexts, by measuring changes in the electric organ
discharge (EOD) frequency. Specifically, we focused on envelopes, which can arise
either because of movement (i.e. motion envelopes) or because of interactions
between the electric fields of three of more fish (i.e. social envelopes).
Overall, we found that the animal's EOD frequency effectively tracked the
detailed time course of both motion and social envelopes. In general, behavioral
sensitivity (i.e. gain) decreased while phase lag increased with increasing
envelope and carrier frequency. However, changes in gain and phase lag as a
function of changes in carrier frequency were more prominent for motion than for
social envelopes in general. Importantly, we compared behavioral responses to
motion and social envelopes with similar characteristics. Although behavioral
sensitivities were similar, we observed an increased response lag for social
envelopes, primarily for low carrier frequencies. Thus, our results imply that
the organism can, based on behavioral responses, distinguish envelope stimuli
resulting from movement from those that instead result from social interactions.
We discuss the implications of our results for neural coding of envelopes and
propose that behavioral responses to motion and social envelopes are mediated by
different neural circuits in the brain.
PMID- 29954833
TI - Yra1-bound RNA-DNA hybrids cause orientation-independent transcription
replication collisions and telomere instability.
AB - R loops are an important source of genome instability, largely due to their
negative impact on replication progression. Yra1/ALY is an abundant RNA-binding
factor conserved from yeast to humans and required for mRNA export, but its
excess causes lethality and genome instability. Here, we show that, in addition
to ssDNA and ssRNA, Yra1 binds RNA-DNA hybrids in vitro and, when artificially
overexpressed, can be recruited to chromatin in an RNA-DNA hybrid-dependent
manner, stabilizing R loops and converting them into replication obstacles in
vivo. Importantly, an excess of Yra1 increases R-loop-mediated genome instability
caused by transcription-replication collisions regardless of whether they are
codirectional or head-on. It also induces telomere shortening in telomerase
negative cells and accelerates senescence, consistent with a defect in telomere
replication. Our results indicate that RNA-DNA hybrids form transiently in cells
regardless of replication and, after stabilization by excess Yra1, compromise
genome integrity, in agreement with a two-step model of R-loop-mediated genome
instability. This work opens new perspectives to understand transcription
associated genome instability in repair-deficient cells, including tumoral cells.
PMID- 29954836
TI - Comprehensive ADP-ribosylome analysis identifies tyrosine as an ADP-ribose
acceptor site.
AB - Despite recent mass spectrometry (MS)-based breakthroughs, comprehensive ADP
ribose (ADPr)-acceptor amino acid identification and ADPr-site localization
remain challenging. Here, we report the establishment of an unbiased, multistep
ADP-ribosylome data analysis workflow that led to the identification of tyrosine
as a novel ARTD1/PARP1-dependent in vivo ADPr-acceptor amino acid. MS analyses of
in vitro ADP-ribosylated proteins confirmed tyrosine as an ADPr-acceptor amino
acid in RPS3A (Y155) and HPF1 (Y238) and demonstrated that trans-modification of
RPS3A is dependent on HPF1. We provide an ADPr-site Localization Spectra Database
(ADPr-LSD), which contains 288 high-quality ADPr-modified peptide spectra, to
serve as ADPr spectral references for correct ADPr-site localizations.
PMID- 29954837
TI - Equilibrium Assays Are Required to Accurately Characterize the Activity Profiles
of Drugs Modulating Gq-Protein-Coupled Receptors.
AB - This paper discusses the process of determining the activity of candidate
molecules targeting Gq-protein activation through G-protein-coupled receptors for
possible therapeutic application with two functional assays; calcium release and
inositol phosphate metabolism [inositol monophosphate (IP1)]. While both are
suitable for detecting ligand activity (screening), differences are seen when
these assays are used to quantitatively measure ligand parameters for therapeutic
activity. Specifically, responses for Gq-related pathways present different and
dissimulating patterns depending on the functional assay used to assess them. To
investigate the impact of functional assays on the accuracy of compound
pharmacological profiles, five exemplar molecules [partial agonist, antagonist,
inverse agonist, positive allosteric modulator (PAM) agonist, and positive beta
PAM] targeting either muscarinic M1 or ghrelin receptors were tested using two
functional assays (calcium release and IP1) and the results were compared with
theoretical pharmacological models. The IP1 assay is an equilibrium assay that is
able to determine the correct (i.e., internally consistent) pharmacological
profiles of all tested compounds. In contrast, the nonequilibrium nature of
calcium assays yields misleading classification of most of the tested compounds.
Our study suggests that the use of an equilibrium assay, such as IP1, is
mandatory for the optimal use of pharmacological models that can both identify
mechanisms of action and also convert descriptive-to-predictive data for
therapeutic systems. Such assays allow the identification of consistent and
simple scales of activity that can guide medicinal chemistry in lead optimization
of candidate molecules for therapeutic use.
PMID- 29954838
TI - Febrile Infant Hospitalizations: When Is the Right Time to Discharge?
PMID- 29954839
TI - Time to Pathogen Detection for Non-ill Versus Ill-Appearing Infants <=60 Days Old
With Bacteremia and Meningitis.
AB - OBJECTIVES: We sought to determine the time to pathogen detection in blood and
cerebrospinal fluid (CSF) for infants <=60 days old with bacteremia and/or
bacterial meningitis and to explore whether time to pathogen detection differed
for non-ill-appearing and ill-appearing infants. METHODS: We included infants
<=60 days old with bacteremia and/or bacterial meningitis evaluated in the
emergency departments of 10 children's hospitals between July 1, 2011, and June
30, 2016. The microbiology laboratories at each site were queried to identify
infants in whom a bacterial pathogen was isolated from blood and/or CSF. Medical
records were then reviewed to confirm the presence of a pathogen and to extract
demographic characteristics, clinical appearance, and the time to pathogen
detection. RESULTS: Among 360 infants with bacteremia, 316 (87.8%) pathogens were
detected within 24 hours and 343 (95.3%) within 36 hours. A lower proportion of
non-ill-appearing infants with bacteremia had a pathogen detected on blood
culture within 24 hours compared with ill-appearing infants (85.0% vs 92.9%,
respectively; P = .03). Among 62 infants with bacterial meningitis, 55 (88.7%)
pathogens were detected within 24 hours and 59 (95.2%) were detected within 36
hours, with no difference based on ill appearance. CONCLUSIONS: Among infants
<=60 days old with bacteremia and/or bacterial meningitis, pathogens were
commonly identified from blood or CSF within 24 and 36 hours. However, clinicians
must weigh the potential for missed bacteremia in non-ill-appearing infants
discharged within 24 hours against the overall low prevalence of infection.
PMID- 29954841
TI - Erratum. Insulin Access and Affordability Working Group: Conclusions and
Recommendations. Diabetes Care 2018;41;1299-1311.
PMID- 29954840
TI - Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder
cancer: a whole-exome sequencing analysis.
AB - OBJECTIVES: Patients with gallbladder carcinoma (GBC) lack effective treatment
methods largely due to the inadequacy of both molecular characterisation and
potential therapeutic targets. We previously uncovered a spectrum of genomic
alterations and identified recurrent mutations in the ErbB pathway in GBC. Here,
we aimed to study recurrent mutations of genes and pathways in a larger cohort of
patients with GBC and investigate the potential mechanisms and clinical
significance of these mutations. DESIGN: We performed whole-exome sequencing
(WES) in 157 patients with GBC. Functional experiments were applied in GBC cell
lines to explore the oncogenic roles of ERBB2/ERBB3 hotspot mutations, their
correlation with PD-L1 expression and the underlying mechanisms. ERBB inhibitors
and a PD-L1 blocker were used to evaluate the anticancer activities in co-culture
systems in vitro and in vivo. RESULTS: WES identified ERBB2 and ERBB3 mutations
at a frequency of 7%-8% in the expanded cohort, and patients with ERBB2/ERBB3
mutations exhibited poorer prognoses. A set of in vitro and in vivo experiments
revealed increased proliferation/migration on ERBB2/ERBB3 mutation. Ectopic
expression of ERBB2/ERBB3 mutants upregulated PD-L1 expression in GBC cells,
effectively suppressed normal T-cell-mediated cytotoxicity in vitro through
activation of the PI3K/Akt signalling pathway and contributed to the growth and
progression of GBC in vivo. Treatment with an ERBB2/ERBB3 inhibitor or a PD-L1
monoclonal antibody reversed these immunosuppressive effects, and combined
therapy revealed promising therapeutic activities. CONCLUSIONS: ERBB2/ERBB3
mutations may serve as useful biomarkers in identifying patients who are
sensitive to ERBB2/ERBB3 inhibitors and PD-L1 monoclonal antibody treatment.
TRIAL REGISTRATION NUMBER: NCT02442414;Pre-results.
PMID- 29954842
TI - Genetic Analysis of Signal Generation by the Rgt2 Glucose Sensor of Saccharomyces
cerevisiae.
AB - The yeast S. cerevisiae senses glucose through Snf3 and Rgt2, transmembrane
proteins that generate an intracellular signal in response to glucose that leads
to inhibition of the Rgt1 transcriptional repressor and consequently to
derepression of HXT genes encoding glucose transporters. Snf3 and Rgt2 are
thought to be glucose receptors because they are similar to glucose transporters.
In contrast to glucose transporters, they have unusually long C-terminal tails
that bind to Mth1 and Std1, paralogous proteins that regulate function of the
Rgt1 transcription factor. We show that the C-terminal tail of Rgt2 is not
responsible for its inability to transport glucose. To gain insight into how the
glucose sensors generate an intracellular signal, we identified RGT2 mutations
that cause constitutive signal generation. Most of the mutations alter
evolutionarily-conserved amino acids in the transmembrane spanning regions of
Rgt2 that are predicted to be involved in maintaining an outward-facing
conformation or to be in the substrate binding site. Our analysis of these
mutations suggests they cause Rgt2 to adopt inward-facing or occluded
conformations that generate the glucose signal. These results support the idea
that Rgt2 and Snf3 are glucose receptors that signal in response to binding of
extracellular glucose and inform the basis of their signaling.
PMID- 29954845
TI - Interaction of the cryptic fragment of myelin basic protein with mitochondrial
voltage-dependent anion-selective channel-1 affects cell energy metabolism.
AB - In demyelinating nervous system disorders, myelin basic protein (MBP), a major
component of the myelin sheath, is proteolyzed and its fragments are released in
the neural environment. Here, we demonstrated that, in contrast with MBP, the
cellular uptake of the cryptic 84-104 epitope (MBP84-104) did not involve the low
density lipoprotein receptor-related protein-1, a scavenger receptor. Our pull
down assay, mass spectrometry and molecular modeling studies suggested that,
similar with many other unfolded and aberrant proteins and peptides, the
internalized MBP84-104 was capable of binding to the voltage-dependent anion
selective channel-1 (VDAC-1), a mitochondrial porin. Molecular modeling suggested
that MBP84-104 directly binds to the N-terminal alpha-helix located midway inside
the 19 beta-blade barrel of VDAC-1. These interactions may have affected the
mitochondrial functions and energy metabolism in multiple cell types. Notably,
MBP84-104 caused neither cell apoptosis nor affected the total cellular ATP
levels, but repressed the aerobic glycolysis (lactic acid fermentation) and
decreased the l-lactate/d-glucose ratio (also termed as the Warburg effect) in
normal and cancer cells. Overall, our findings implied that because of its
interactions with VDAC-1, the cryptic MBP84-104 peptide invoked reprogramming of
the cellular energy metabolism that favored enhanced cellular activity, rather
than apoptotic cell death. We concluded that the released MBP84-104 peptide,
internalized by the cells, contributes to the reprogramming of the energy
generating pathways in multiple cell types.
PMID- 29954843
TI - RAD Sequencing and a Hybrid Antarctic Fur Seal Genome Assembly Reveal Rapidly
Decaying Linkage Disequilibrium, Global Population Structure and Evidence for
Inbreeding.
AB - Recent advances in high throughput sequencing have transformed the study of wild
organisms by facilitating the generation of high quality genome assemblies and
dense genetic marker datasets. These resources have the potential to
significantly advance our understanding of diverse phenomena at the level of
species, populations and individuals, ranging from patterns of synteny through
rates of linkage disequilibrium (LD) decay and population structure to individual
inbreeding. Consequently, we used PacBio sequencing to refine an existing
Antarctic fur seal (Arctocephalus gazella) genome assembly and genotyped 83
individuals from six populations using restriction site associated DNA (RAD)
sequencing. The resulting hybrid genome comprised 6,169 scaffolds with an N50 of
6.21 Mb and provided clear evidence for the conservation of large chromosomal
segments between the fur seal and dog (Canis lupus familiaris). Focusing on the
most extensively sampled population of South Georgia, we found that LD decayed
rapidly, reaching the background level by around 400 kb, consistent with other
vertebrates but at odds with the notion that fur seals experienced a strong
historical bottleneck. We also found evidence for population structuring, with
four main Antarctic island groups being resolved. Finally, appreciable variance
in individual inbreeding could be detected, reflecting the strong polygyny and
site fidelity of the species. Overall, our study contributes important resources
for future genomic studies of fur seals and other pinnipeds while also providing
a clear example of how high throughput sequencing can generate diverse biological
insights at multiple levels of organization.
PMID- 29954844
TI - Complex rearrangements and oncogene amplifications revealed by long-read DNA and
RNA sequencing of a breast cancer cell line.
AB - The SK-BR-3 cell line is one of the most important models for HER2+ breast
cancers, which affect one in five breast cancer patients. SK-BR-3 is known to be
highly rearranged, although much of the variation is in complex and repetitive
regions that may be underreported. Addressing this, we sequenced SK-BR-3 using
long-read single molecule sequencing from Pacific Biosciences and develop one of
the most detailed maps of structural variations (SVs) in a cancer genome
available, with nearly 20,000 variants present, most of which were missed by
short-read sequencing. Surrounding the important ERBB2 oncogene (also known as
HER2), we discover a complex sequence of nested duplications and translocations,
suggesting a punctuated progression. Full-length transcriptome sequencing further
revealed several novel gene fusions within the nested genomic variants. Combining
long-read genome and transcriptome sequencing enables an in-depth analysis of how
SVs disrupt the genome and sheds new light on the complex mechanisms involved in
cancer genome evolution.
PMID- 29954846
TI - Differential Representation of Landmark and Self-Motion Information along the CA1
Radial Axis: Self-Motion Generated Place Fields Shift toward Landmarks during
Septal Inactivation.
AB - Spatial location in the environment can be defined in relation to specific
landmarks or in relation to the global context, and is estimated from both the
sensing of landmarks and the inner sense of cumulated locomotion referred to as
path-integration. The respective contribution of landmark and path-integration to
place-cell activity in the hippocampus is still unclear and complicated by the
fact that the two mechanisms usually overlap. To bias spatial mechanisms toward
landmark or path-integration, we use a treadmill equipped with a long belt on
which male mice run sequentially through a zone enriched and a zone impoverished
in visual-tactile cues. We show that inactivation of the medial septum (MS),
which is known to disrupt the periodic activity of grid cells, impairs mice
ability to anticipate the delivery of a reward in the cue-impoverished zone and
transiently alter the spatial configuration of place fields in the cue
impoverished zone selectively: following MS inactivation, place fields in the cue
impoverished zone progressively shift backward and stabilize near the cues,
resulting in the contraction of the spatial representation around cues; following
MS recovery, the initial spatial representation is progressively restored.
Furthermore, we found that place fields in the cue-rich and cue-impoverished
zones are preferentially generated by cells from the deep and superficial
sublayers of CA1, respectively. These findings demonstrate with mechanistic
insights the contribution of MS to the spread of spatial representations in cue
impoverished zones, and indicate a segregation of landmark-based and path
integration-assisted spatial mechanisms into deep and superficial CA1,
respectively.SIGNIFICANCE STATEMENT Cells encoding a cue-impoverished zone and
the vicinity of landmarks responded differentially to septal inactivation and
resided in distinct sublayers of CA1. These findings provide new insights on
place field mechanisms: septal activity is critical for maintaining the spread of
place fields in cue-impoverished areas, but not for the generation of place
fields; Following MS inactivation, trial-by-trial network modifications by
activity-dependent mechanisms are responsible for the gradual collapse of spatial
representations. Furthermore, the findings suggest parallel coding streams for
landmark and self-motion information. Superficial CA1 cells are better suited for
encoding global position via the assist of path-integration, whereas deep CA1
cells can support spatial memory processes on an object-specific basis.
PMID- 29954847
TI - VIP-immunoreactive interneurons within circuits of the mouse basolateral
amygdala.
AB - In cortical structures, principal cell activity is tightly regulated by different
GABAergic interneurons (INs). In particular, vasoactive intestinal polypeptide
expressing (VIP+) INs innervate preferentially other INs, providing a structural
basis for temporal disinhibition of principal cells. However, relatively little
is known about VIP+ INs in the amygdaloid basolateral complex (BLA). In this
study, we report that VIP+ INs have a variable density in the distinct
subdivisions of the mouse BLA. Based on different anatomical, neurochemical and
electrophysiological criteria, VIP+ INs could be identified as interneuron
selective INs and basket cells expressing CB1 cannabinoid receptors. Whole-cell
recordings of VIP+ interneuron-selective INs revealed 3 different spiking
patterns, which did not associate with the expression of calretinin. Genetic
targeting combined with optogenetics and in vitro recordings allowed us to
identify several types of BLA INs innervated by VIP+ INs, including other
interneuron-selective INs, basket and neurogliaform cells. Moreover, light
stimulation of VIP+ basket cell axon terminals, characterized by CB1 sensitivity,
evoked IPSPs in ~20% of principal neurons. Finally, we show that VIP+ INs receive
a dense innervation from both GABAergic, although only 10% from other VIP+ INs,
and distinct glutamatergic inputs, identified by their expression of different
vesicular glutamate transporters.In conclusion, our study provides a wide-range
analysis of single-cell properties of VIP+ INs in the mouse BLA and of their
intrinsic and extrinsic connectivity. Our results reinforce the knowledge that
VIP+ INs are structurally and functionally heterogeneous and that this
heterogeneity could mediate different roles in amygdala-dependent
functions.Significance statement:We provide the first comprehensive analysis of
the distribution of VIP+ interneurons across the entire mouse BLA, as well as of
their morphological and physiological properties. VIP+ interneurons in the
neocortex preferentially target other interneurons to form a disinhibitory
network that facilitates principal cell firing. Our study is the first to
demonstrate the presence of such a disinhibitory circuitry in the BLA. We
observed structural and functional heterogeneity of these INs and characterized
their input/output connectivity. We also identified several types of BLA
interneurons postsynaptic to VIP+ INs, whose inhibition may provide a temporal
window for principal cell firing and facilitate associative plasticity, e.g. in
fear learning. Disinhibition, thus, is emerging as a general mechanism, not
limited to the neocortex.
PMID- 29954848
TI - Chrna5-expressing neurons in the interpeduncular nucleus mediate aversion primed
by prior stimulation or nicotine exposure.
AB - Genetic studies have shown an association between smoking and variation at the
CHRNA5/A3/B4 gene locus, encoding the alpha5, alpha3 and beta4 nicotinic receptor
subunits. The alpha5 receptor has been specifically implicated because smoking
associated haplotypes contain a coding variant in the CHRNA5 gene. The
Chrna5/a3/b4 locus is conserved in rodents, and the restricted expression of
these subunits suggests neural pathways through which the reinforcing and
aversive properties of nicotine may be mediated. Here we show that in the
interpeduncular nucleus (IP), the site of the highest Chrna5 mRNA expression in
rodents, electrophysiological responses to nicotinic acetylcholine receptor
stimulation are markedly reduced in alpha5 null mice. In this regard, we find IP
neurons differ markedly from their upstream ventral medial habenula cholinergic
partners, which appear unaltered by loss of alpha5. To probe the functional role
of alpha5-containing IP neurons, we used BAC recombineering to generate
transgenic mice expressing Cre-recombinase from the Chrna5 locus. Reporter
expression driven by Chrna5Cre demonstrates that transcription of Chrna5 is
regulated independently from the Chrna3/b4 genes, transcribed on the opposite
strand. Chrna5-expressing IP neurons are GABAergic and project to distant targets
in the mesopontine raphe and tegmentum, rather than forming local circuits.
Optogenetic stimulation of Chrna5-expressing IP neurons failed to elicit physical
manifestations of withdrawal. However, following recent prior stimulation or
exposure to nicotine, IP stimulation becomes aversive. These results using mice
of both sexes support the idea that the risk allele of CHRNA5 may increase the
drive to smoke via loss of IP-mediated nicotine aversion.SIGNIFICANCE
STATEMENTUnderstanding the receptors and neural pathways underlying the
reinforcing and aversive effects of nicotine may suggest new treatments for
tobacco addiction. Part of the individual variability in smoking is associated
with specific forms of the alpha5 nicotinic receptor subunit gene. Here we show
that deletion of the alpha5 subunit in mice markedly reduces the cellular
response to nicotine and acetylcholine in the interpeduncular nucleus (IP).
Stimulation of alpha5-expressing IP neurons using optogenetics is aversive, but
this effect requires priming by recent prior stimulation or exposure to
nicotine.. These results support the idea that the smoking-associated variant of
the alpha5 gene may increase the drive to smoke via loss of IP-mediated nicotine
aversion.
PMID- 29954849
TI - Orbitofrontal Signaling of Future Reward is Associated with Hyperactivity in
Attention-Deficit/Hyperactivity Disorder.
AB - Alterations in motivated behavior are a hallmark of attention
deficit/hyperactivity disorder (ADHD), one of the most common psychiatric
disorders in children and adolescents. The orbitofrontal cortex (OFC) plays a key
role in controlling goal-directed behavior, but the link between OFC dysfunction
and behavioral deficits in ADHD, particularly in adolescence, remains poorly
understood. Here we used advanced high-resolution functional magnetic resonance
imaging (fMRI) of the human OFC in adolescents with ADHD and typically developing
(TD) controls (N = 39, age 12-16, all male except for one female per group) to
study reward-related OFC responses and how they relate to behavioral dysfunction
in ADHD. During fMRI data acquisition, participants performed a simple decision
making task, allowing us to image expectation-related responses to small and
large monetary outcomes. Across all participants, we observed significant signal
increases to large versus small expected rewards in the OFC. These responses were
significantly enhanced in ADHD relative to TD participants. Moreover, stronger
reward-related activity was correlated with individual differences in
hyperactive/impulsive symptoms in the ADHD group, whereas high cognitive ability
was associated with normalized OFC responses. These results provide evidence for
the importance of OFC dysfunctions in the neuropathology of ADHD, highlighting
the role of OFC-dependent goal-directed control mechanisms in this
disorder.SIGNIFICANCE STATEMENT Attention-deficit/hyperactivity disorder (ADHD)
is characterized by alterations in motivated behavior which can be understood as
diminished goal-directed control. The orbitofrontal cortex (OFC) plays a key role
in controlling goal-directed behavior, but its potential contribution to ADHD
symptomatology remains poorly understood. Using high-resolution fMRI, we show
that adolescent ADHD patients display enhanced OFC signaling of future rewards
and that these increased reward-related responses are correlated with the
severity of hyperactivity/impulsivity. These findings suggest that an inability
to adequately evaluate future outcomes may translate into maladaptive behavior in
ADHD patients. They also challenge the idea that dysfunctions in dopaminergic
brain areas are the sole contributor to reward-related symptoms in ADHD and point
to a central contribution of goal-directed control circuits in hyperactivity.
PMID- 29954850
TI - Intranasal wnt3a Attenuates Neuronal Apoptosis through Frz1/PIWIL1a/FOXM1 Pathway
in MCAO Rats.
AB - After ischemic stroke, apoptosis of neurons is a primary factor in determining
outcome. Wnt3a is a naturally occurring protein that has been shown to have
protective effects in the brain for traumatic brain injury. Although wnt3a has
been investigated in the phenomena of neurogenesis, anti-apoptosis, and anti
inflammation, it has never been investigated as a therapy for stroke. We
hypothesized that the potential neuroprotective agent wnt3a would reduce
infarction and improve behavior following ischemic stroke by attenuating neuronal
apoptosis and promoting cell survival through the Frizzled-1/PIWI1a/FOXM1 pathway
in middle cerebral artery occlusion (MCAO) rats. A total of 229 Sprague Dawley
rats were assigned to male, female, and 9-month-old male MCAO or sham groups
followed by reperfusion 2 h after MCAO. Animals assigned to MCAO were either
given wnt3a or its control. To explore the downstream signaling of wnt3a, the
following interventions were given: Frizzled-1 siRNA, PIWI1a siRNA, and PIWI1a
clustered regularly interspaced short palindromic repeats, along with the
appropriate controls. Post-MCAO assessments included neurobehavioral tests,
infarct volume, Western blot, and immunohistochemistry. Endogenous levels of
wnt3a and Frizzled-1/PIWI1a/FOXM1 were lowered after MCAO. The administration of
intranasal wnt3a, 1 h after MCAO, increased PIWIL1a and FOXM1 expression through
Frizzled-1, reducing brain infarction and neurological deficits at 24 and 72 h.
Frizzled-1 and PIWI1a siRNAs reversed the protective effects of wnt3a after MCAO.
Restoration of PIWI1a after knockdown of Frizzled-1 increased FOXM1 survival
protein and reduced cleaved caspase-3 levels. In summary, wnt3a decreases
neuronal apoptosis and improves neurological deficits through Frizzled
1/PIWI1a/FOXM1 pathway after MCAO in rats. Therefore, wnt3a is a novel intranasal
approach to decrease apoptosis after stroke.SIGNIFICANCE STATEMENT Only 5% of
patients receive recombinant tissue plasminogen activator after stroke, and few
qualify for mechanical thrombectomy. No neuroprotective agents have been
successfully translated to promote neuronal survival in stroke. Thus, using a
clinically relevant rat model of stroke, middle cerebral artery occlusion, we
explored a novel intranasal administration of wnt3a. wnt3a naturally occurs in
the body and crosses the blood-brain barrier, supporting the clinically
translatable approach of intranasal administration. Significant neuronal
apoptosis occurs during stroke, and wnt3a shows promise due to its antiapoptotic
effects. We investigated whether wnt3a mediates its poststroke effects via
Frizzled-1 and the impact on its downstream signaling molecules, PIWI1a and
FOXM1, in apoptosis. Elucidating the mechanism of wnt3a will identify additional
pharmacological targets and further understanding of stroke.
PMID- 29954851
TI - "A hierarchy of time scales for discriminating and classifying the temporal shape
of sound in three auditory cortical fields".
AB - Auditory cortex is essential for mammals, including rodents, to detect temporal
"shape" cues in the sound envelope but it remains unclear how different cortical
fields may contribute to this ability (Threlkeld et al, 2008; Malhotra, 2008).
Previously, we found precise spiking patterns provide a potential neural code for
temporal shape cues in the sound envelope in primary (A1) and ventral (VAF) and
caudal suprarhinal (cSRAF) auditory fields of the rat (Lee et al., 2016). Here,
we extend these findings and characterize the time course of the temporally
precise output of auditory cortical neurons in male rats. A pairwise sound
discrimination index and a Naive Bayesian classifier are used to determine how
these spiking patterns could provide brain signals for behavioral discrimination
and classification of sounds. We find response durations and optimal time
constants for discriminating sound envelope shape increase in rank order with: A1
< VAF 0.70). The highest AUC
value (0.932) was produced from a risk model developed for patients with mild
cognitive impairment. CONCLUSION: The predictive ability of existing dementia
risk models is acceptable. Population-specific dementia risk models are necessary
for populations and subpopulations with different characteristics.
PMID- 29954872
TI - Acute EEG spectra characteristics predict thalamic atrophy after severe TBI.
PMID- 29954873
TI - Mutation screening of the KIF5A gene in Chinese patients with amyotrophic lateral
sclerosis.
PMID- 29954874
TI - How important is social support in determining patients' suitability for
transplantation? Results from a National Survey of Transplant Clinicians.
AB - BACKGROUND: National guidelines require programmes use subjective assessments of
social support when determining transplant suitability, despite limited evidence
linking it to outcomes. We examined how transplant providers weigh the importance
of social support for kidney transplantation compared with other factors, and
variation by clinical role and personal beliefs. METHODS: The National survey of
the American Society of Transplant Surgeons and the Society of Transplant Social
Work in 2016. Using a discrete choice approach, respondents compared two
hypothetical patient profiles and selected one for transplantation. Conditional
logistic regression estimated the relative importance of each factor; results
were stratified by clinical role (psychosocial vs medical/surgical providers) and
beliefs (outcomes vs equity). RESULTS: Five hundred and eighy-four transplant
providers completed the survey. Social support was the second most influential
factor among transplant providers. Providers were most likely to choose a
candidate who had social support (OR=1.68, 95% CI 1.50 to 1.86), always adhered
to a medical regimen (OR=1.64, 95% CI 1.46 to 1.88), and had a 15 years life
expectancy with transplant (OR=1.61, 95% CI 1.42 to 1.85). Psychosocial providers
were more influenced by adherence and quality of life compared with
medical/surgical providers, who were more influenced by candidates' life
expectancy with transplant (p<0.05). For providers concerned with avoiding organ
waste, social support was the most influential factor, while it was the least
influential for clinicians concerned with fairness (p<0.05). CONCLUSIONS: Social
support is highly influential in listing decisions and may exacerbate transplant
disparities. Providers' beliefs and reliance on social support in determining
suitability vary considerably, raising concerns about transparency and justice.
PMID- 29954875
TI - In the patient's best interest: appraising social network site information for
surrogate decision making.
AB - This paper will discuss why and how social network sites ought to be used in
surrogate decision making (SDM), with focus on a context like Singapore in which
substituted judgment is incorporated as part of best interest assessment for SDM,
as guided by the Code of Practice for making decisions for those lacking mental
capacity under the Mental Capacity Act (2008). Specifically, the paper will argue
that the Code of Practice already supports an ethical obligation, as part of a
patient-centred care approach, to look for and appraise social network site (SNS)
as a source of information for best interest decision making. As an important
preliminary, the paper will draw on Berg's arguments to support the use of SNS
information as a resource for SDM. It will also supplement her account for how
SNS information ought to be weighed against or considered alongside other
evidence of patient preference or wishes, such as advance directives and
anecdotal accounts by relatives.
PMID- 29954876
TI - Cerebral organoids and consciousness: how far are we willing to go?
PMID- 29954877
TI - Sexual health prevention for incarcerated women: eroticising safe sex during re
entry to the community.
AB - INTRODUCTION: In the USA, incarcerated women are disproportionately affected by
sexually transmitted infections (STIs) including HIV. Transitioning from
incarceration into the community is accompanied by elevated risk behaviours
related to acquisition of STIs, yet few efficacious interventions address sexual
health prevention among incarcerated women. METHODS: We conducted an exploratory
qualitative study with 21 incarcerated women at four women's state prison
facilities in two Northeastern states in the USA. Qualitative data were gathered
from four focus groups to guide future intervention development. Focus group
discussions were guided by a semi-structured protocol exploring perceptions of
sexual health prevention methods, experience with implementing prevention
technologies and protective behaviours, and strategies to overcome challenges in
implementing sexual health prevention behaviours. Focus groups were audio
recorded and transcribed verbatim. Data were analysed using thematic analysis.
RESULTS: Women described challenges in uptake of existing low-cost sexual health
prevention strategies such as condoms. They identified strategies to facilitate
use of prevention tools, and to increase protective behaviours relating to sexual
health during the transition from incarceration to the community. For example,
women described methods for eroticising male and female condoms, including
selecting condoms with novel features, explaining to partners that condoms could
increase sexual pleasure, and incorporating condom application into foreplay
and/or oral sex. CONCLUSION: Incorporating these insights, including how to
eroticise safe sex, can inform the design of future preventive interventions
tailored to meet the urgent sexual health needs of incarcerated women preparing
for reintegration into the community. CLINICAL TRIAL REGISTRATION: NCT01907126.
PMID- 29954878
TI - Factors associated with first-year discontinuation of Implanon in Upper Egypt:
clients' and providers' perspectives.
AB - BACKGROUND: The etonogestrel implant Implanon is a favourable and cost-effective
contraceptive method for women in developing countries, and expansion of its use
represents a priority for the family planning (FP) programme in Egypt. We studied
the factors affecting first-year Implanon discontinuation from clients' and
providers' perspectives. METHODS: We used a mixed quantitative-qualitative
methodology. We conducted a household survey of Implanon clients and three focus
group discussions with FP physicians and directors. RESULTS: We found that 13.5%
of Implanon users discontinued its use in the first year. Survival analysis found
that clients who had previously used Implanon (HR 0.36, 95% CI 0.15 to 0.88) and
whose husbands had secondary or a higher level of education (HR 0.36,95% CI 0.19
to 0.69) were less likely to discontinue Implanon use after the first year, while
clients who experienced side effects of Implanon use were more likely to
discontinue it (HR 3.6,95% CI 1.60 to 8.11). Other causes of discontinuation
which emerged in the qualitative analysis were the unjustified advice for
Implanon removal by non-gynaecologists, due to unrelated users' complaints, and
deficient pre-insertion counselling. CONCLUSIONS: Implanon has a low first-year
discontinuation rate as compared with other contraceptive methods. FP clients
should be given sufficient pre-insertion counselling about side effects of
Implanon and duration of protection. Physicians should offer Implanon mainly to
clients seeking long-term contraception in order to decrease its discontinuation
rate and increase its cost effectiveness.
PMID- 29954879
TI - Extending non-invasive prenatal testing to non-invasive prenatal diagnosis.
PMID- 29954880
TI - Breastfeeding outcomes in European NICUs: impact of parental visiting policies.
AB - OBJECTIVE: The documented benefits of maternal milk for very preterm infants have
raised interest in hospital policies that promote breastfeeding. We investigated
the hypothesis that more liberal parental policies are associated with increased
breastfeeding at discharge from the neonatal unit. DESIGN: Prospective area-based
cohort study. SETTING: Neonatal intensive care units (NICUs) in 19 regions of 11
European countries. PATIENTS: All very preterm infants discharged alive in
participating regions in 2011-2012 after spending >70% of their hospital stay in
the same NICU (n=4407). MAIN OUTCOME MEASURES: We assessed four feeding outcomes
at hospital discharge: any and exclusive maternal milk feeding, independent of
feeding method; any and exclusive direct breastfeeding, defined as sucking at the
breast. We computed a neonatal unit Parental Presence Score (PPS) based on
policies regarding parental visiting in the intensive care area (range 1-10, with
higher values indicating more liberal policies), and we used multivariable
multilevel modified Poisson regression analysis to assess the relation between
unit PPS and outcomes. RESULTS: Policies regarding visiting hours, duration of
visits and possibility for parents to stay during medical rounds and spend the
night in unit differed within and across countries. After adjustment for
potential confounders, infants cared for in units with liberal parental policies
(PPS>=7) were about twofold significantly more likely to be discharged with
exclusive maternal milk feeding and exclusive direct breastfeeding. CONCLUSION:
Unit policies promoting parental presence and involvement in care may increase
the likelihood of successful breastfeeding at discharge for very preterm infants.
PMID- 29954882
TI - T-piece resuscitators: a warning sign.
PMID- 29954881
TI - Epidemiology of infections and antimicrobial use in Greek Neonatal Units.
AB - OBJECTIVE: To describe the epidemiology of neonatal infections and of
antimicrobial use in Greek Neonatal Units (NNUs) in order to develop national,
evidence-based guidelines on empiric antimicrobial use for neonatal sepsis in
Greece. DESIGN: Retrospective analysis of prospectively collected infection
surveillance data from 2012 to 2015, together with a Point Prevalence Survey
(PPS) on antimicrobial use and the collection of data on local empiric
antimicrobial policies. SETTING: 16 NNUs in Greece participating in the neonIN
infection surveillance network PATIENTS: Newborns in participating NNUs who had a
positive blood, cerebrospinal fluid or urine culture and were treated with at
least 5 days of antibiotics. RESULTS: 459 episodes were recorded in 418 infants.
The overall incidence of infection was 50/1000 NNU-admissions. The majority of
episodes were late-onset sepsis (LOS) (413, 90%). Coagulase-negative
Staphylococci (80%) were the most common Gram-positive organisms causing LOS and
Klebsiella spp (39%) the most common Gram-negative. Nearly half (45%) of the
Klebsiella spp were resistant to at least one aminoglycoside. The PPS revealed
that 196 of 484 (40%) neonates were on antimicrobials. The survey revealed wide
variation in empiric antimicrobial policies for LOS. CONCLUSIONS: This is the
largest collection of data on the epidemiology of neonatal infections in Greece
and on neonatal antimicrobial use. It provides the background for the development
of national evidence-based guidelines. Continuous surveillance, the introduction
of antimicrobial stewardship interventions and evidence-based guidelines are
urgently required.
PMID- 29954883
TI - Complete Genome Sequences of a Diverse Group of 13 Propionibacterium acnes
Bacteriophages Isolated from Urban Raw Sewage.
AB - We present complete genome sequences of 13 Propionibacterium acnes phages
isolated from urban raw sewage. They belong to the family Siphoviridae, have
genome sizes of 29,450.6 +/- 256.5 nucleotides and G+C contents of 54.14% +/-
0.22% and contain 42 to 45 coding DNA sequences (CDS). Genomic sequences of 9 of
13 phages were divergent by 6 to 10%, distinguishing them as species.
PMID- 29954884
TI - Whole-Genome Sequence of Salmonella enterica subsp. enterica Serovar Typhimurium
Strain WG49 and Escherichia coli Strain WG5 Used in South Africa for Phage
Detection in Water Samples.
AB - Salmonella enterica subsp. enterica serovar Typhimurium WG49 is widely used for
enumeration of F-specific RNA (F-RNA) coliphages in water. Escherichia coli WG5
is broadly used for the detection and enumeration of somatic coliphages in water
samples. We report here the genome sequences of these bacterial strains used in
South Africa under ISO methods 10705-1 and 10705-2.
PMID- 29954885
TI - Full-Length Genome Sequence of a Sindbis Virus Strain Isolated from Culex
cinereus in 1977 in Bozo, Central African Republic.
AB - We report here the complete genome sequence of a Sindbis virus (SINV) strain,
ArB7761, isolated in 1977 in the Central African Republic. This strain, closely
related to the Babanki virus, belongs to the SINV genotype I clade. However, it
differs from the Egyptian prototype strain AR339 by several indels in the nsP3
gene.
PMID- 29954886
TI - Complete Genome Sequences of Two Chikungunya Viruses Imported into China.
AB - Here, we isolated two chikungunya virus strains (SZ1050 and SZ1239) from patients
infected with chikungunya virus who were returning to China from India and
Indonesia, respectively. Strain SZ1050 was classed in the Indian Ocean lineage,
and strain SZ1239 belonged to the Asian lineage. No A226V mutation in the
envelope protein E1 was found in either strain.
PMID- 29954887
TI - Recovery of Five Complete Influenza A(H1N1)pdm09 Genome Sequences from the 2015
Influenza Outbreak in India by Metagenomic Sequencing.
AB - Five complete (H1N1)pdm09 viral sequences were recovered from hospitalized
individuals during the 2015 influenza outbreak by metagenomic sequencing. Four of
the genomes are from oropharyngeal swabs, and one is from an isolate. All five
sequences belong to an emerging 6B clade. Studying them further is critical for
outbreak preparedness.
PMID- 29954888
TI - High-Quality Genome Sequence of the Root-Knot Nematode Meloidogyne arenaria
Genotype A2-O.
AB - Root-knot nematodes (Meloidogyne spp.) cause serious damage to many crops
globally. We report the high-quality genome sequence of Meloidogyne arenaria
genotype A2-O. The genome assembly of M. arenaria A2-O is composed of 2,224
contigs with an N50 contig length of 204,551 bp and a total assembly length of
284.05 Mb.
PMID- 29954889
TI - Closed Genome Sequence of Clostridium botulinum Strain CFSAN064329 (62A).
AB - Clostridium botulinum is a strictly anaerobic, Gram-positive, spore-forming
bacterium that produces botulinum neurotoxin, a potent and deadly proteinaceous
exotoxin. Clostridium botulinum strain CFSAN064329 (62A) produces an A1
serotype/subtype botulinum neurotoxin and is frequently utilized in food
challenge and detection studies. We report here the closed genome sequence of
Clostridium botulinum strain CFSAN064329 (62A).
PMID- 29954890
TI - Draft Genome Assemblages of 10 Xanthomonas vasicola pv. zeae Strains, Pathogens
Causing Leaf Streak Disease of Maize in South Africa.
AB - Maize bacterial leaf streak disease has spread across maize crops in South Africa
and therefore potentially poses a threat to maize production and food security.
Until recently, this pathogen was identified as a Xanthomonas campestris
pathovar, whereas our South African genomes seem to be more divergent and create
their own subclade.
PMID- 29954891
TI - Whole-Genome Shotgun Sequencing of Three Listeria monocytogenes Strains Isolated
from a Ready-to-Eat Salad-Producing Facility in Switzerland.
AB - Ready-to-eat (RTE) raw foods harbor the risk of transmitting Listeria
monocytogenes from the environment to the consumer. We isolated three strains
from a facility producing RTE salad. These strains were used to perform challenge
tests on different RTE salad products. Here, we present the shotgun genome
sequences of all three of these strains.
PMID- 29954892
TI - Complete Genome Sequence of a Bluetongue Virus Serotype 15 Strain Isolated from
China in 1996.
AB - The full-genome sequence of bluetongue virus serotype 15 (BTV-15) strain
B105/YN/1996 isolated in China was determined for the first time. The virus was
isolated from sentinel cattle in Yunnan Province, China, in 1996. The total size
of the BTV-15 strain B105/YN/1996 genome is 19,161 bp in length. Phylogenetic
analyses demonstrate that it belongs to the major eastern BTV topotype. This work
is the first to document the complete genomic sequence of a BTV-15 strain from
China. The sequence information will help determine the geographic origin of
Chinese BTV-15 and provide data to facilitate future analyses of the genetic
diversity and phylogenetic relationships of BTV strains.
PMID- 29954893
TI - Complete Genome Sequence of Acinetobacter schindleri SGAir0122 Isolated from
Singapore Air.
AB - Acinetobacter schindleri strain SGAir0122 was isolated from tropical air samples
collected in Singapore. The prevalence of nosocomial infection caused by this
Gram-negative bacterium indicates its clinical significance as an opportunistic
human pathogen. Its complete genome consists of one chromosome of 3.105 Mb and a
plasmid of 181 kb.
PMID- 29954894
TI - Complete Genome Sequence of the Novel Virulent Phage PMBT28 with Lytic Activity
against Thermotolerant Salmonella enterica subsp. enterica Serovar Senftenberg
ATCC 43845.
AB - The complete genome sequence of the novel virulent Siphoviridae phage PMBT28,
which may potentially be utilized for the biocontrol of Salmonella spp., is
reported here. The phage was isolated using Salmonella enterica subsp. enterica
serovar Senftenberg ATCC 43845 as a bacterial host. The genome had no significant
sequence similarity to known phage genomes.
PMID- 29954895
TI - Draft Genome Sequence of the Antimicrobial-Producing Strain Paenibacillus elgii
AC13.
AB - A Paenibacillus elgii strain isolated from soil samples from Cerrado, Brazil,
showed antimicrobial activity. Its genome sequence was acquired (GS20 FLX
Titanium 454 platform) and comprises 108 contigs (N50, 198,427 bp) and 6,810
predicted sequences. Here, we shed some light on the antimicrobial genes of the
strain, including a nonribosomal peptide synthetase (NRPS) module identified as
part of a pelgipeptin gene cluster.
PMID- 29954896
TI - Complete Genome Sequencing of Two Equine Influenza A(H3N8) Virus Strains Isolated
in Kazakhstan.
AB - Here, we report the complete genome sequencing of strains
A/equine/Kostanay/9/2012(H3N8) and A/equine/LKZ/9/2012(H3N8) of the equine
influenza virus belonging to Florida sublineage, clade 2. The strains were
isolated in 2012 in the northern and southern regions of Kazakhstan,
respectively.
PMID- 29954897
TI - Draft Genome Sequence of Mycoplasma arginini Strain NGR_2017.
AB - We present the draft genome of Mycoplasma arginini strain NGR_2017. This strain
was recovered in Nigeria from cell culture in 2017. The assembly contains 620,555
bp in 12 contigs. It contains 561 coding sequences, 34 RNAs (29 tRNAs, 4 rRNAs,
and 1 transfer-messenger RNA [tmRNA]), and a >26-kb integrative and conjugative
element.
PMID- 29954898
TI - Complete Genome Sequence of a Tilapia Lake Virus Isolate Obtained from Nile
Tilapia (Oreochromis niloticus).
AB - Since its discovery in 2014, tilapia lake virus (TiLV) has emerged as a
significant cause of mortality in tilapia cultured in Asia, Africa, and South
America. Here, we report the complete genome sequence of a TiLV isolate obtained
during a diagnostic investigation of an ongoing mortality event involving Nile
tilapia cultured in Thailand.
PMID- 29954899
TI - Genome Sequence of Acetomicrobium hydrogeniformans OS1.
AB - Acetomicrobium hydrogeniformans, an obligate anaerobe of the phylum
Synergistetes, was isolated from oil production water. It has the unusual ability
to produce almost 4 molecules H2/molecule glucose. The draft genome of A.
hydrogeniformans OS1 (DSM 22491T) is 2,123,925 bp, with 2,068 coding sequences
and 60 RNA genes.
PMID- 29954900
TI - Complete Genome Sequences of Two T4-Like Escherichia coli Bacteriophages.
AB - Bacteriophages and their proteins have potential applications in biotechnology
for the detection and control of bacterial diseases. Here, we describe the
sequencing and genome annotations of two strictly virulent Escherichia coli
bacteriophages that may be explored for biocontrol strategies and to expand the
understanding of phage-host interactions.
PMID- 29954901
TI - Draft Genome Sequences of Six Skin Isolates of Streptococcus pyogenes.
AB - Whole-genome shotgun sequences and bottom-up assembly of contigs of six skin
isolates of Streptococcus pyogenes, viz, NS88.3 (emm98.1), NS223 (emm91), NS455
(emm52), SS1448 (emm86.2), SS1572 (emm223), and SS1574 (emm224), are presented
here. All contigs were annotated, and the gene arrangements and the inferred
proteins were consistent with a pattern D classification.
PMID- 29954902
TI - Complete Genome Sequence of an Avian Native NDM-1-Producing Salmonella enterica
subsp. enterica Serovar Corvallis Strain.
AB - Carbapenems are an important class of beta-lactams and one of the last options
for treating severe human infections. We present here the complete genome
sequence of avian native carbapenemase-producing Salmonella enterica subsp.
enterica serovar Corvallis strain 12-01738, harboring a blaNDM-1-carrying IncA/C2
plasmid, isolated in 2012 from a wild bird (Milvus migrans) in Germany.
PMID- 29954903
TI - Complete Draft Genome Sequence of an Extended-Spectrum beta-Lactamase-Producing
Citrobacter freundii Strain Recovered from the Intestine of a House Sparrow
(Passer domesticus) in Germany, 2017.
AB - Here, we announce the genome of an extended-spectrum beta-lactamase-producing
Citrobacter freundii strain isolated from the cecum of a house sparrow that was
found dead in Berlin-Lichtenberg, Germany, in 2017. This isolate exhibits
increased MICs for several antimicrobials and a comprehensive set of acquired
resistance determinants potentially involved in horizontal gene transfer.
PMID- 29954904
TI - Draft Genome Sequences of Two Edwardsiella piscicida Strains, JF1307 and JF1411,
Isolated from Diseased Olive Flounder (Paralichthys olivaceus) Cultured in Japan.
AB - Edwardsiella piscicida strains JF1307 and JF1411 were isolated from cultured
olive flounder that were diagnosed as being infected with edwardsiellosis. The
draft genome sequences of the two isolates comprise 3,882,000 bp and 3,827,424 bp
with G+C contents of 59.5% and 59.6%, respectively.
PMID- 29954905
TI - Draft Genome Sequence of Bacillus altitudinis Lc5, a Biocontrol and Plant Growth
Promoting Endophyte Strain Isolated from Indigenous Black Rice of Manipur.
AB - We report here the 3.6-Mb draft genome of Bacillus altitudinis Lc5, a potential
plant growth promoter and an active antagonistic endophyte of black rice. This
genome study will provide better insights into the strain's mechanisms for plant
growth promotion and biocontrol, thus facilitating its application in organic
agriculture.
PMID- 29954906
TI - Draft Genome Sequence of a White Spot Syndrome Virus Isolate Obtained in Ecuador.
AB - White spot syndrome virus (WSSV) is the most devastating viral disease affecting
cultivated shrimp around the world. Currently, there is no reported genetic
information on WSSV affecting Penaeus vannamei in Ecuador. Therefore, we
determined the genome of a WSSV isolate from shrimp and compared it with the
genomes of isolates from other geographical locations.
PMID- 29954907
TI - Draft Genome Sequences of Bifidobacterium Strains Isolated from Dietary
Supplements and Cultured Food Products.
AB - Here, we present the genome sequences of 23 Bifidobacterium isolates from several
commercially available dietary supplements and cultured food products. Strains of
this genus are natural inhabitants of the mammalian mouth, gastrointestinal
tract, and vagina. Some species are considered beneficial to human health.
PMID- 29954908
TI - Draft Genome Sequence of Vibrio harveyi Strain GAN1709, Isolated from Diseased
Greater Amberjack (Seriola dumerili) Farmed in Japan.
AB - Vibrio harveyi strain GAN1709 was isolated from a diseased greater amberjack
farmed in Nomi Bay, Japan. Here, we report the draft genome sequence of this
strain, which comprises 6,265,473 bp, with a G+C content of 44.8%.
PMID- 29954909
TI - Draft Genome Sequence of Phosphate-Solubilizing Chryseobacterium sp. Strain
ISE14, a Biocontrol and Plant Growth-Promoting Rhizobacterium Isolated from
Cucumber.
AB - Chryseobacterium sp. strain ISE14 is a phosphate-solubilizing endophytic
bacterium that exhibits plant growth promotion and biocontrol activities against
Phytophthora blight and anthracnose on pepper. Here, we report the draft genome
sequence of strain ISE14, which contains genes relating to phosphate
solubilization, plant growth promotion, and biocontrol traits.
PMID- 29954910
TI - Genome Sequence of Torulaspora microellipsoides CLIB 830T.
AB - We report here the genome sequence of the ascomycetous yeast Torulaspora
microellipsoides CLIB 830T A reference genome for this species, which has been
found as a donor of genetic material in wine strains of Saccharomyces cerevisiae,
will undoubtedly give clues to our understanding of horizontal transfer
mechanisms between species in the wine environment.
PMID- 29954911
TI - Genome Sequences of Five Lactobacillus sp. Isolates from Traditional Turkish
Sourdough.
AB - A high level of variation in microflora can be observed in profiles of lactic
acid bacteria (LAB) from sourdoughs. Here, we present draft genome sequences of
Lactobacillus reuteri E81, L. reuteri LR5A, L. rhamnosus LR2, L. plantarum PFC
311, and the novel Lactobacillus sp. strain PFC-70, isolated from traditional
Turkish backslopped wheat sourdoughs.
PMID- 29954912
TI - Complete Genome Sequence of Streptomyces sp. Strain BSE7F, a Bali Mangrove
Sediment Actinobacterium with Antimicrobial Activities.
AB - The strain Streptomyces sp. BSE7F, a novel Streptomyces strain isolated from
Indonesian mangrove sediment, displays antimicrobial activities against Gram
positive bacteria, Gram-negative bacteria, and yeast. Bioinformatic analysis of
the genome sequence revealed the occurrence of 22 biosynthetic gene clusters
disclosing the secondary metabolite capacity of strain BSE7F.
PMID- 29954913
TI - Draft Genome Sequence of a Potentially Novel Streptococcus Species Belonging to
the Streptococcus mitis Group.
AB - We report here the draft genome sequence of a Streptococcus species belonging to
the S. mitis group. While a clear species identification cannot be made for the
isolate, it appears that its most recent common ancestor is the species S.
pseudopneumoniae.
PMID- 29954914
TI - Fifty-Six Draft Genome Sequences of 10 Lactobacillus Species from 22 Commercial
Dietary Supplements.
AB - Here, we present the genome sequences of 56 isolates of 10 species of the genus
Lactobacillus that are considered beneficial components of the gut microbiota.
The isolates examined were found in commercially available dietary supplements in
the U.S. market.
PMID- 29954915
TI - Genome Sequence of Staphylococcus aureus Ex1, Isolated from a Patient with Spinal
Osteomyelitis.
AB - Here, we present the genome sequence of Staphylococcus aureus Ex1, isolated in
2015 from a patient with spinal osteomyelitis at the Royal Devon and Exeter
Hospital in the United Kingdom. The availability of the Ex1 genome sequence
provides a resource for studying the basis for spinal infection and horizontal
gene transfer in S. aureus.
PMID- 29954916
TI - Genome Sequence of the Soybean Cyst Nematode (Heterodera glycines) Endosymbiont
"Candidatus Cardinium hertigii" Strain cHgTN10.
AB - In this study, we present the genome sequence of the "Candidatus Cardinium
hertigii" strain cHgTN10, an endosymbiotic bacterium of the plant-parasitic
nematode Heterodera glycines This is the first genome assembly reported for an
endosymbiont directly sequenced from a tylenchid nematode.
PMID- 29954917
TI - Draft Genome Sequences of Chryseobacterium lactis NCTC11390T Isolated from Milk,
Chryseobacterium oncorhynchi 701B-08T from Rainbow Trout, and Chryseobacterium
viscerum 687B-08T from Diseased Fish.
AB - The genus Chryseobacterium, belonging to the family Flavobacteriaceae, contains
Gram-negative, yellow-pigmented, rod-shaped, and non-spore-forming bacterial
species, which may be free living or parasitic. Here, we report draft genome
sequences of type strains of three species of Chryseobacterium containing genes
related to biological control and plant growth promotion.
PMID- 29954918
TI - Complete Genome Sequences of Four Salmonella enterica subsp. enterica Serovar
Senftenberg and Montevideo Isolates Associated with a 2016 Multistate Outbreak in
the United States.
AB - A multistate outbreak of 11 Salmonella infections linked to pistachio nuts
occurred in 2016. In this announcement, we report the complete genome sequences
of four Salmonella enterica subsp. enterica serovar Senftenberg and S. enterica
subsp. enterica serovar Montevideo isolates from pistachios collected during the
2016 outbreak investigation.
PMID- 29954919
TI - Draft Genome Sequences of Two Novel Cellulolytic Streptomyces Strains Isolated
from South African Rhizosphere Soil.
AB - We report here the draft genome sequences of two novel strains of Streptomyces
(NWU339 and NWU49) isolated from South African rhizosphere soils. Both strains
were found to possess strong cellulolytic activity and contain numerous putative
cellulase genes. Both genomes possess benzoate degradation pathways, while NWU49
contains the genomic potential for enediyne biosynthesis.
PMID- 29954920
TI - Systematic review and meta-analysis of interventions aimed at enhancing return to
work for sick-listed workers with common mental disorders, stress-related
disorders, somatoform disorders and personality disorders.
AB - OBJECTIVES: Mental disorders are associated with significant functional
impairment, sickness absence and disability. The consequences of sickness absence
warrant investigation into interventions aimed at enhancing return to work (RTW)
for workers with mental disorders. The present systematic review and meta
analysis aim to synthesise evidence on the effectiveness of interventions aimed
at enhancing RTW in sick-listed workers with mental disorders. METHODS: EconLit,
Embase, PsychInfo, PubMed, Svemed+ and Web of Science were searched for peer
reviewed, randomised or controlled studies assessing employment-related outcomes
of interventions. A meta-analysis was conducted and meta-regressions were
performed to explore prespecified potential sources of heterogeneity between
studies. RESULTS: The literature search yielded 3777 publications of which 42
(n=38 938) were included in the systematic review and 32 (n=9459) had appropriate
data for the meta-analysis. The pooled effect size (95 % CI) was 0.14 (0.07 to
0.22). Meta-regressions revealed that the heterogeneity could not be attributed
to study quality, timing of the intervention or length of the intervention.
However, it could be partly explained by number of components included in the
intervention, if the intervention included contact to the work place and by the
disorder targeted by the intervention. CONCLUSIONS: The results reveal strong
evidence for interventions including contact to the work place and multicomponent
interventions and moderate evidence for interventions including graded RTW. In
addition, the results provide strong evidence for interventions targeting stress
compared with interventions targeting other mental disorders. The findings point
to important implications for policy and design of future interventions.
PMID- 29954921
TI - Evaluation of an ATP-Bioluminescence Rapid Microbial Screening Method for In
Process Biologics.
AB - This study compared an adenosine triphosphate (ATP)-based bioluminescence rapid
microbial method (RMM) with a conventional sterility method for biologics sample
testing. The RMM is based on a comparison of ATP levels in inoculated and
uninoculated microbiological growth medium samples following growth enrichment
incubation. The biologics samples qualified in this study were recombinant
monoclonal antibodies and hybridoma cell culture supernatants. Initially, the lot
to-lot variation in background ATP of these samples posed significant challenges.
Two strategies to increase the signal-to-noise ratio (positive result/background
ATP) were evaluated: enzyme-based signal amplification and reduction of the broth
based noise through broth selection. Following qualification of the RMM for
antibody and cell culture samples, the RMM was also utilized for rapid screening
of several sources of purified water. This ATP-based RMM has proved invaluable in
routine testing of diverse biologics samples at our discovery research site and
plays a key role in the investigation of contaminated samples.LAY ABSTRACT:
Biologics research laboratories routinely conduct sterility testing of products
in development. However, the lengthy turnaround time for detection of microbial
contaminants when using a conventional sterility test is a bottleneck in this
fast-paced environment. This study investigated an adenosine triphosphate-based
bioluminescence rapid microbial method (RMM) for biologics samples, including
monoclonal antibodies and hybridoma cell cultures. The results showed that the
RMM allowed detection of antibody sample contaminants after only three days of
incubation. In addition to being faster than the standard method, the RMM proved
more reliable in detecting contaminants in cell culture samples with antibiotics.
Since its initial evaluation, this RMM has accelerated biologics sterility
testing across multiple projects at our site.
PMID- 29954922
TI - The Boil Test-Strategies for Resistance Determination of Microorganisms.
AB - The terminal sterilization of drugs and devices is the most appropriate means of
assuring patient safety in terms of infection prevention. Adoption of terminal
sterilization processes requires a supporting and thorough program for control
and monitoring of bioburden, especially if a parametric release program of
sterilization is desired. Such a control program should necessarily assess and
evaluate the associated bioburden (primarily spores), which may resist
inactivation and challenge the sterilization cycle. The bioburden resistance can
be evaluated by several means and procedures (e.g., the boil test); however,
these procedures should be designed and implemented taking into consideration the
nature of the spore and spore recovery. This short review describes the
application of moist heat resistance for the terminal sterilization of drugs.LAY
ABSTRACT: The terminal sterilization of drugs and devices is the most appropriate
means of assuring patient safety in terms of infection prevention. Adoption of
terminal sterilization processes requires a supporting and thorough program for
control and monitoring of bioburden, especially if a parametric release program
of sterilization is desired. This short review describes the application of moist
heat resistance for the terminal sterilization of drugs.
PMID- 29954923
TI - Delamination Propensity of Glass Containers for Pharmaceutical Use: A Round Robin
Activity Looking for a Predictive Test.
AB - Delamination, which is the formation of flakes in drug products owing to specific
and localized corrosion of glass vials, is a rare but serious problems, on which
the FDA (U.S. Food and Drug Administration) put a warning to the pharma industry
in 2011. The Technical Committee (TC) TC12 of the International Commission on
Glass (ICG) was created in 2012 with the aim to study the problems related to
pharma packaging. The first task of TC12 was to address the problem of predicting
the propensity of glass vials to delamination, leaving the study of the
mechanism(s) of flake formation as a possible future activity. This paper reports
on the results obtained in a round robin test, which involved all the labs of the
companies represented in the TC.Five types of vials with different expected
delamination propensities were tested using a protocol that includes autoclaving
at 121 degrees C of vials filled with NaCl solution adjusted to pH 8 with NaOH
solution, a coloration test, and ICP-OES determination of Si, B, and Al.Although
there was no flake formation, the results showed that the combination of strong
coloration at the bottom of the vials and high silicon concentration in the
solution is correlated to an observable morphological modification/corrosion of
the inner surface of vials in the bottom region. The test protocol is therefore
useful for checking the quality of the vials with respect to the propensity to
corrosion. Regarding delamination, no direct correlation with the testing results
could be obtained yet. The method allows catching differences in the corrosion
behavior, mainly between sets of vials with comparable surface:volume.LAY
ABSTRACT: The U.S. Food and Drug Administration (FDA) warned the pharma industry
about glass delamination inside primary packaging containers. Delamination is a
type of glass corrosion that produces glass flakes, which could seriously affect
patient health.Fortunately, delamination is a very rare event. On the other hand,
it is very difficult to predict its occurrence. In 2012, the International
Commission on Glass (ICG) created a Technical Committee (TC) on pharma packaging
with the initial goal to study an easy and reliable test for predicting the
propensity of vials to delamination-involving the most important glass vial
producers and pharma companies. This paper reports on the results obtained in a
round robin test on different types of vials with different expected propensities
to delamination. A specific testing protocol was adopted. In none of the vials,
including those with an expected high propensity, glass flakes were observed,
demonstrating that delamination is a rare event. However, the test is able to
predict the occurrence of morphological modification/corrosion of the inner
surface of vials in the bottom region. Therefore, the testing protocol is
proposed as a method to evaluate differences in the corrosion behavior mainly
between sets of vials with comparable surface:volume.
PMID- 29954924
TI - Quantifying the Vial Capping Process: Residual Seal Force and Container Closure
Integrity.
AB - Capping completes the closure of parenteral drug products in the final packaging
container and is critical in maintaining an integral seal to ensure product
quality. Residual seal force (RSF) is considered the sole quantifiable attribute
for measuring seal ?goodness? and potentially enables non-subjective, consistent
setting of cappers across manufacturing sites. However, the consistency and
reliability of RSF measurement and data have been scarcely reported, and the
relationship between RSF and container closure integrity (CCI) remains poorly
understood. Here, we present a large data set generated from a commercial capper
and the results from a laboratory capper of glass vials and rubber stoppers with
aluminum caps. All RSF values exhibited significant variability. We evaluated
three potential sources of variability: the capper, the RSF Tester, and the
components. We determined that the capper and Tester are not main sources.
Dimensional tolerances of the packaging components were the root cause. This
study correlated RSF with CCI (via helium leakage) although CCI is not sensitive
to RSF; CCI was maintained even for loosely capped vials with no measurable RSF.
This was attributed to the stopper?s two sealing surfaces: the valve seal and the
land seal. A methodology capable of differentiating the two seals? functions
demonstrated that vials with only the valve seal always passed leakage testing,
while vials with only the land seal failed CCI at low RSF values. This
observation allows proposal of a low RSF limit that is safe even when the valve
seal is defective. Statistical analysis of commercial capping data, with the
input of sample size, allowed the relationship between RSF?s low limit and an
allowable failing rate to be established. Overall, despite the inherent
variability of RSF, this study shows that it is a feasible parameter for capping
process quantification and demonstrates the potential of RSF measurement in
capper setup.
PMID- 29954925
TI - Lower DHEA-S levels predict disease and worse outcomes in post-menopausal women
with idiopathic, connective tissue disease- and congenital heart disease
associated pulmonary arterial hypertension.
AB - High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are
risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex
hormones are related to PAH in women is unknown.Post-menopausal women aged >=55
years with PAH were matched by age and body mass index to women without
cardiovascular disease. Plasma sex hormone levels were measured by
immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02)
were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were
associated with worse haemodynamics (all p<0.01) and more right ventricular
dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated
with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class
(p=0.004). Each Ln(1 ug.dL-1) decrease in DHEA-S was associated with a doubling
in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels
of E2 were associated with shorter 6MWD (p=0.03) and worse functional class
(p=0.01).High E2 and low DHEA-S levels are associated with the risk and severity
of PAH in post-menopausal women. Hormonal modulation should be studied as a
treatment strategy in PAH.
PMID- 29954926
TI - Obstructive sleep apnoea and exercise functional capacity: time to move?
PMID- 29954927
TI - Beyond oestrogens: towards a broader evaluation of the hormone profile in
pulmonary arterial hypertension.
PMID- 29954929
TI - Daratumumab for relapsed/refractory Philadelphia-positive acute lymphoblastic
leukemia.
PMID- 29954928
TI - Pharmacological modulation of CXCR4 cooperates with BET bromodomain inhibition in
diffuse large B-cell lymphoma.
AB - Constitutive activation of the chemokine receptor CXCR4 has been associated with
tumor progression, invasion, and chemotherapy resistance in different cancer
subtypes. Although the CXCR4 pathway has recently been suggested as an adverse
prognostic marker in diffuse large B-cell lymphoma, its biological relevance in
this disease remains underexplored. In a homogeneous cohort of 52 patient
biopsies, an antibody-based cytokine array showed that tissue levels of CXCL12
correlated with high microvessel density and bone marrow involvement at
diagnosis, supporting a role for CXCL12-CXCR4 axis in disease progression. We
then identified the tetra-amine IQS-01.01RS as a potent inverse agonist of the
receptor, preventing CXCL12-mediated chemotaxis and triggering apoptosis in a
panel of 18 cell lines and primary cultures, with superior mobilizing properties
in vivo than standard agent. IQS-01.01RS activity was associated with
downregulation of p-AKT, p-ERK1/2 and destabilization of MYC, allowing to a
synergistic interaction with the bromodomain and extra-terminal domain inhibitor,
CPI203. In a xenotransplant model of diffuse large B-cell lymphoma, IQS
01.01RS/CPI203 combination decreased tumor burden through MYC and p-AKT
downregulation, and enhanced apoptosis induction. Thus, our results point out an
emerging role of CXCL12-CXCR4 in the pathogenesis of diffuse large B-cell
lymphoma and support the simultaneous targeting of CXCR4 and bromodomain proteins
as a promising, rationale-based strategy for this disease.
PMID- 29954930
TI - Immunomodulatory drugs downregulate IKZF1 leading to expansion of hematopoietic
progenitors with concomitant block of megakaryocytic maturation.
AB - The immunomodulatory drugs, lenalidomide and pomalidomide yield high response
rates in multiple myeloma patients, but are associated with a high rate of
thrombocytopenia and increased risk of secondary hematologic malignancies. Here,
we demonstrate that the immunomodulatory drugs induce self-renewal of
hematopoietic progenitors and upregulate megakaryocytic colonies by inhibiting
apoptosis and increasing proliferation of early megakaryocytic progenitors via
down-regulation of IKZF1. In this process, the immunomodulatory drugs degrade
IKZF1 and subsequently down-regulate its binding partner, GATA1. This results in
the decrease of GATA1 targets such as ZFPM1 and NFE2, leading to expansion of
megakaryocytic progenitors with concomitant inhibition of maturation of
megakaryocytes. The down-regulation of GATA1 further decreases CCND1 and
increases CDKN2A expression. Overexpression of GATA1 abrogated the effects of the
immunomodulatory drugs and restored maturation of megakaryocytic progenitors. Our
data not only provide the mechanism for the immunomodulatory drugs induced
thrombocytopenia but also help to explain the higher risk of secondary
malignancies and long-term cytopenia induced by enhanced cell cycling and
subsequent exhaustion of the stem cell pool.
PMID- 29954931
TI - A phase II/III randomized, multicenter trial of prednisone/sirolimus versus
prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft
versus-host disease: BMT CTN 0801.
AB - Initial therapy of chronic graft-versus-host disease is prednisone +/- a
calcineurin-inhibitor, but most patients respond inadequately. In a randomized,
adaptive, phase II/III, multicenter trial we studied whether prednisone/sirolimus
or prednisone/sirolimus/photopheresis was more effective than
prednisone/sirolimus/calcineurin-inhibitor for treating chronic graft-versus-host
disease in treatment-naive or early inadequate responders. Primary endpoints of
this study were proportions of subjects alive without relapse or secondary
therapy with 6-month complete or partial response in phase II, or with 2-year
complete response in phase III. The prednisone/sirolimus/photopheresis arm closed
prematurely because of slow accrual and the remaining two-drug versus three-drug
study ended in phase II due to statistical futility with 138 evaluable subjects.
The two-drug and three-drug arms did not differ in rates of 6-month complete or
partial response (48.6% versus 50.0%, P=0.87), or 2-year complete response (14.7%
versus 15.5%, P=0.90). Serum creatinine values >1.5 times baseline were less
frequent in the calcineurin-inhibitor-free arm at 2 months (1.5% versus 11.7%,
P=0.025) and 6 months (7.8% versus 24.0%, P=0.016). Higher adjusted Short Form-36
Physical Component Summary and Physical Functioning scores were seen in the two
drug arm at both 2 months (P=0.02 and P=0.04, respectively) and 6 months (P=0.007
and P=0.001, respectively). Failure-free survival and overall survival rates at 2
years were similar for patients in the the two-drug and three-drug arms (48.6%
versus 46.2%, P=0.78; 81.5% versus 74%, P=0.28). Based on similar long-term
outcomes, prednisone/sirolimus is a therapeutic alternative to
prednisone/sirolimus/calcineurin-inhibitor for chronic graft-versus-host disease,
being easier to administer and better tolerated. Clinicaltrials.gov identifier:
NCT01106833.
PMID- 29954932
TI - A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan
prednisone induction followed by single-agent ixazomib maintenance in transplant
ineligible newly diagnosed multiple myeloma.
AB - This phase I/II dose-escalation study investigated the all-oral ixazomib
melphalan-prednisone regimen, followed by single-agent ixazomib maintenance, in
elderly, transplant-ineligible patients with newly diagnosed multiple myeloma.
Primary phase I objectives were to determine the safety and recommended phase II
dose of ixazomib-melphalan-prednisone. The primary phase II objective was to
determine the complete plus very good partial response rate. In phase I, patients
were enrolled to 4 arms investigating weekly or twice-weekly ixazomib (13 28-day
cycles or nine 42-day cycles) plus melphalan-prednisone. In phase II, an
expansion cohort was enrolled at the recommended phase II ixazomib dose. Of the
61 patients enrolled, 26 received the recommended phase II dose (ixazomib 4.0 mg
[days 1, 8, 15] plus melphalan-prednisone 60 mg/m2 [days 1-4], 28-day cycles). Of
the 61 enrolled patients, 36 (13 of 26 in the recommended phase II dose cohort)
received single-agent ixazomib maintenance (days 1, 8, 15; 28-day cycles). In
phase I, 10/38 patients reported dose-limiting toxicities in cycle 1, including
grade 3 and/or 4 neutropenia (n=6) and thrombocytopenia (n=4). Complete plus very
good partial response rate was 48% (48% at recommended phase II dose), including
28% (22%) complete response or better; responses deepened during maintenance in
34% (33%) of evaluable patients. After median follow up of 43.6 months, median
progression-free survival was 22.1 months. Adverse events were mainly hematologic
events, gastrointestinal events, and peripheral neuropathy. This study
demonstrates the feasibility, tolerability, and activity of ixazomib-melphalan
prednisone induction and single-agent ixazomib maintenance in transplant
ineligible newly diagnosed multiple myeloma patients. clinicaltrials.gov
identifier 01335685.
PMID- 29954933
TI - A comprehensive inventory of TLX1 controlled long non-coding RNAs in T-cell acute
lymphoblastic leukemia through polyA+ and total RNA sequencing.
PMID- 29954934
TI - Impact of Sox11 overexpression in Ba/F3 cells.
PMID- 29954935
TI - Acute myeloid leukemia in very old patients.
PMID- 29954936
TI - Reduced tyrosine kinase inhibitor dose is predicted to be as effective as
standard dose in chronic myeloid leukemia: a simulation study based on phase III
trial data.
AB - Continuing tyrosine kinase inhibitor (TKI)-mediated targeting of the BCR-ABL1
oncoprotein is the standard therapy for chronic myeloid leukemia (CML) and allows
for a sustained disease control in the majority of patients. While therapy
cessation for patients appeared as a safe option for about half of those patients
with optimal response, no systematic assessment of long-term TKI dose de
escalation has been made. We use a mathematical model to analyze and consistently
describe biphasic treatment responses from TKI-treated patients from two
independent clinical phase III trials. Scale estimates reveal that drug
efficiency determines the initial response while the long-term behavior is
limited by the rare activation of leukemic stem cells. We use this mathematical
framework to investigate the influence of different dosing regimens on the
treatment outcome. We provide strong evidence to suggest that TKI dose de
escalation (at least 50%) does not lead to a reduction of long-term treatment
efficiency for most patients, who have already achieved sustained remission, and
maintains the secondary decline of BCR-ABL1 levels. We demonstrate that
continuous BCR-ABL1 monitoring provides patient-specific predictions of an
optimal reduced dose without decreasing the anti-leukemic effect on residual
leukemic stem cells. Our results are consistent with the interim results of the
DESTINY trial and provide clinically testable predictions. Our results suggest
that dose-halving should be considered as a long-term treatment option for CML
patients with good response under continuing maintenance therapy with TKIs. We
emphasize the clinical potential of this approach to reduce treatment-related
side-effects and treatment costs.
PMID- 29954937
TI - Relapse of acute myeloid leukemia after allogeneic stem cell transplantation is
associated with gain of WT1 alterations and high mutation load.
PMID- 29954938
TI - Mutational screening of newly diagnosed multiple myeloma patients by deep
targeted sequencing.
PMID- 29954940
TI - MYC protein expression scoring and its impact on the prognosis of aggressive B
cell lymphoma patients.
PMID- 29954939
TI - Multiple faces of succinate beyond metabolism in blood.
AB - Succinate is an essential intermediate of the tricarboxylic acid cycle that
exerts pleiotropic roles beyond metabolism in both physiological and pathological
conditions. Recent evidence obtained in mouse models shows its essential role
regulating blood cell function through various mechanisms that include
pseudohypoxia responses by hypoxia-inducible factor-1alpha activation, post
translational modifications like succinylation, and communication mediated by
succinate receptor 1. Hence, succinate links metabolism to processes like gene
expression and intercellular communication. Interestingly, succinate plays key
dual roles during inflammatory responses, leading to net inflammation or anti
inflammation depending on factors like the cellular context. Here, we further
discuss current suggestions of the possible contribution of succinate to blood
stem cell function and blood formation. Further study will be required in the
future to better understand succinate biology in blood cells. This promising
field may open new avenues to modulate inflammatory responses and to preserve
blood cell homeostasis in the clinical setting.
PMID- 29954941
TI - Alas1 is essential for neutrophil maturation in zebrafish.
AB - Neutrophils play essential roles in innate immunity and are the first responders
to kill foreign micro-organisms, a function that partially depends on their
granule content. The complicated regulatory network of neutrophil development and
maturation remains largely unknown. Here we utilized neutrophil-deficient
zebrafish to identify a novel role of Alas1, a heme biosynthesis pathway enzyme,
in neutrophil development. We showed that Alas1-deficient zebrafish exhibited
proper neutrophil initiation, but further neutrophil maturation was blocked due
to heme deficiency, with lipid storage and granule formation deficiencies, and
loss of heme-dependent granule protein activities. Consequently, Alas1-deficient
zebrafish showed impaired bactericidal ability and augmented inflammatory
responses when challenged with Escherichia coli These findings demonstrate the
important role of Alas1 in regulating neutrophil maturation and physiological
function through the heme. Our study provides an in vivo model of Alas1
deficiency and may be useful to evaluate the progression of heme-related
disorders in order to facilitate the development of drugs and treatment
strategies for these diseases.
PMID- 29954942
TI - Adherence to the Western, Prudent, and Mediterranean dietary patterns and chronic
lymphocytic leukemia in the MCC-Spain study.
AB - Diet is a modifiable risk factor for several neoplasms but evidence for chronic
lymphocytic leukemia (CLL) is sparse. Previous studies examining the association
between single-food items and CLL risk have yielded mixed results, while few
studies have been conducted on overall diet, reporting inconclusive findings.
This study aimed to evaluate the association between adherence to three dietary
patterns and CLL in the multicase-control study (MCC-Spain) study.
Anthropometric, sociodemographic, medical and dietary information was collected
for 369 CLL cases and 1605 controls. Three validated dietary patterns, Western,
Prudent and Mediterranean, were reconstructed in the MCC-Spain data. The
association between adherence to each dietary pattern and CLL was assessed,
overall and by Rai stage, using mixed logistic regression models adjusted for
potential confounders. High adherence to a Western dietary pattern (i.e. high
intake of high-fat dairy products, processed meat, refined grains, sweets,
caloric drinks, and convenience food) was associated with CLL [ORQ4 vs. Q1=1.63
(95%CI 1.11; 2.39); P-trend=0.02; OR 1-SD increase=1.19 (95%CI: 1.03; 1.37)],
independently of Rai stages. No differences in the association were observed
according to sex, Body Mass Index, energy intake, tobacco, physical activity,
working on a farm, or family history of hematologic malignancies. No associations
were observed for Mediterranean and Prudent dietary patterns and CLL. This study
provides the first evidence for an association between a Western dietary pattern
and CLL, suggesting that a proportion of CLL cases could be prevented by
modifying dietary habits. Further research, especially with a prospective design,
is warranted to confirm these findings.
PMID- 29954943
TI - A genetic model to study O-GlcNAc cycling in immortalized mouse embryonic
fibroblasts.
AB - O-GlcNAcylation is an abundant posttranslational protein modification in which
the monosaccharide O-GlcNAc is added to Ser/Thr residues by O-GlcNAc transferase
and removed by O-GlcNAcase. Analyses of O-GlcNAc-mediated signaling and metabolic
phenomena are complicated by factors including unsatisfactory inhibitors and loss
of-function cell lines lacking identical genetic backgrounds. In this work, we
generated immortalized WT, Oga knockout, and Ogt floxed allele (Ogt floxed) mouse
embryonic fibroblast (MEF) cell lines with similar genetic backgrounds. These
lines will facilitate experiments and serve as a platform to study O-GlcNAc
cycling in mammals. As a test paradigm, we used the immortalized MEF lines to
investigate how changes in O-GlcNAcylation affected pathological phosphorylation
of the tau protein. The activity of glycogen synthase kinase 3beta (GSK3beta), a
kinase that phosphorylates tau, decreases when expressed in Oga knockout MEFs
compared with WT cells. Phosphorylation at Thr231 in recombinant, tauopathy
associated tau with a proline-to-leucine mutation at position 301 (P301L) was
altered when expressed in MEFs with altered O-GlcNAc cycling. In aggregate, our
data support that O-GlcNAc cycling indirectly affects tau phosphorylation at
Thr231, but tau phosphorylation was highly variable, even in genetically stable,
immortalized MEF cells. The variable nature of tau phosphorylation observed here
supports the need to use cells akin to those generated here with genetically
defined lesions and similar backgrounds to study complex biological processes.
PMID- 29954944
TI - Mutant p53 regulates enhancer-associated H3K4 monomethylation through
interactions with the methyltransferase MLL4.
AB - Monomethylation of histone H3 lysine 4 (H3K4me1) is enriched at enhancers that
are primed for activation and the levels of this histone mark are frequently
altered in various human cancers. Yet, how alterations in H3K4me1 are established
and the consequences of these epigenetic changes in tumorigenesis are not well
understood. Using ChIP-Seq in human colon cancer cells, we demonstrate that
mutant p53 depletion results in decreased H3K4me1 levels at active enhancers that
reveal a striking colocalization of mutant p53 and the H3K4 monomethyltransferase
MLL4 following chronic tumor necrosis factor alpha (TNFalpha) signaling. We
further reveal that mutant p53 forms physiological associations and direct
interactions with MLL4 and promotes the enhancer binding of MLL4, which is
required for TNFalpha-inducible H3K4me1 and histone H3 lysine 27 acetylation
(H3K27ac) levels, enhancer-derived transcript (eRNA) synthesis, and mutant p53
dependent target gene activation. Complementary in vitro studies with recombinant
chromatin and purified proteins demonstrate that binding of the MLL3/4 complex
and H3K4me1 deposition is enhanced by mutant p53 and p300-mediated acetylation,
which in turn reflects a MLL3/4-dependent enhancement of mutant p53 and p300
dependent transcriptional activation. Collectively, our findings establish a
mechanism in which mutant p53 cooperates with MLL4 to regulate aberrant enhancer
activity and tumor-promoting gene expression in response to chronic immune
signaling.
PMID- 29954945
TI - O-GlcNAcylation reduces proximal tubule protein reabsorption and promotes
proteinuria in spontaneously hypertensive rats.
AB - Hypertensive individuals are at greater risk for developing chronic kidney
disease (CKD). Reducing proteinuria has been suggested as a possible therapeutic
approach to treat CKD. However, the mechanisms underlying the development of
proteinuria in hypertensive conditions are incompletely understood. Cardiac and
vascular dysfunction is associated with changes in the O-GlcNAcylation pathway in
hypertensive models. We hypothesized that O-GlcNAcylation is also involved in
renal damage, especially development of proteinuria, associated with
hypertension. Using the spontaneously hypertensive rat (SHR) model, we observed
higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT),
and O-GlcNAc transferase (OGT) protein expression, which positively correlated
with proteinuria. Interestingly, this was observed in hypertensive, but not pre
hypertensive, rats. Pharmacological inhibition of GFAT decreased renal cortex O
GlcNAcylation, proteinuria, and albuminuria in SHR. Using a proximal tubule cell
line, we observed that increased O-GlcNAcylation reduced megalin surface
expression and albumin endocytosis in vitro, and the effects were correlated in
vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion,
our results demonstrate a new mechanism involved in hypertension-associated
proteinuria.
PMID- 29954946
TI - Pore properties of Orai1 calcium channel dimers and their activation by the STIM1
ER calcium sensor.
AB - Store-operated Ca2+ entry signals are mediated by plasma membrane Orai channels
activated through intermembrane coupling with Ca2+-sensing STIM proteins in the
endoplasmic reticulum (ER). The nature of this elaborate Orai-gating mechanism
has remained enigmatic. Based on the Drosophila Orai structure, mammalian Orai1
channels are hexamers comprising three dimeric subunit pairs. We utilized
concatenated Orai1 dimers to probe the function of key domains within the channel
pore and gating regions. The Orai1-E106Q selectivity-filter mutant, widely
considered a dominant pore blocker, was surprisingly nondominant within
concatenated heterodimers with Orai1-WT. The Orai1-E106Q/WT heterodimer formed
STIM1-activated nonselective cation channels with significantly enlarged apparent
pore diameter. Other Glu-106 substitutions entirely blocked the function of
heterodimers with Orai1-WT. The hydrophobic pore-lining mutation V102C, which
constitutively opens channels, was suppressed by Orai1-WT in the heterodimer. In
contrast, the naturally occurring R91W pore-lining mutation associated with human
immunodeficiency was completely dominant-negative over Orai-WT in heterodimers.
Heterodimers containing the inhibitory K85E mutation extending outward from the
pore helix gave an interesting partial effect on both channel activation and
STIM1 binding, indicating an important allosteric link between the cytosolic
Orai1 domains. The Orai1 C-terminal STIM1-binding domain mutation L273D
powerfully blocked STIM1-induced channel activation. The Orai1-L273D/WT
heterodimer had drastically impaired STIM1-induced channel gating but,
unexpectedly, retained full STIM1 binding. This reveals the critical role of Leu
273 in transducing the STIM1-binding signal into the allosteric conformational
change that initiates channel gating. Overall, our results provide important new
insights into the role of key functional domains that mediate STIM1-induced
gating of the Orai1 channel.
PMID- 29954948
TI - Speaking up about patient safety concerns: the influence of safety management
approaches and climate on nurses' willingness to speak up.
AB - BACKGROUND: Speaking up is important for patient safety, but healthcare
professionals often hesitate to voice their concerns. Direct supervisors have an
important role in influencing speaking up. However, good insight into the
relationship between managers' behaviour and employees' perceptions about whether
speaking up is safe and worthwhile is still lacking. AIM: To explore the
relationships between control-based and commitment-based safety management,
climate for safety, psychological safety and nurses' willingness to speak up.
METHODS: We conducted a cross-sectional survey study, resulting in a sample of
980 nurses and 93 nurse managers working in Dutch clinical hospital wards. To
test our hypotheses, hierarchical regression analyses (at ward level) and
multilevel regression analyses were conducted. RESULTS: Significantly positive
associations were found between nurses' perceptions of control-based safety
management and climate for safety (beta=0.74; p<0.001), and between the perceived
levels of commitment-based management and team psychological safety (beta=0.36;
p<0.01). Furthermore, team psychological safety is found to be positively related
to nurses' speaking up attitudes (B=0.24; t=2.04; p<0.05). The relationship
between nurse-rated commitment-based safety management and nurses' willingness to
speak up is fully mediated by team psychological safety. CONCLUSION: Results
provide initial support that nurses who perceive higher levels of commitment
based safety management feel safer to take interpersonal risks and are more
willing to speak up about patient safety concerns. Furthermore, nurses'
perceptions of control-based safety management are found to be positively related
to a climate for safety, although no association was found with speaking up. Both
control-based and commitment-based management approaches seem to be relevant for
managing patient safety, but when it comes to encouraging speaking up, a
commitment-based safety management approach seems to be most valuable.
PMID- 29954947
TI - Myeloid-derived growth factor is a resident endoplasmic reticulum protein.
AB - Human myeloid-derived growth factor (MYDGF; also known as C19orf10) is named
based on its identification as a secreted monocyte/macrophage-derived mediator of
cardiac repair following myocardial infarction in mice. Homologs of MYDGF,
however, are present in organisms throughout and outside of the animal kingdom,
some of which lack hematopoietic and circulatory systems. Moreover, the UPF0556
protein domain, which defines these homologs, lacks a known structure. As a
result, the functions and properties of MYDGF are unclear. Our current work was
initiated to test whether MYDGF is present in secretory vesicles of eosinophils
as it was recently reported to be abundant in these cells. However, we could not
demonstrate secretion and unexpectedly discovered that MYDGF colocalizes with
P4HB in the nuclear envelope, which comprises the bulk of endoplasmic reticulum
(ER) in eosinophils, and with P4HB and RCAS1 in Golgi. We noted a ubiquitous C
terminal sequence, BXEL (B, basic; X, variable residue; E, Glu; L, Leu), that has
the potential to retain human MYDGF and its homologs in the ER. To test the
functionality of this sequence, we expressed full-length human MYDGF or MYDGF
lacking the C-terminal Glu-Leu residues in monolayers of human embryonic kidney
293 (HEK293) cells. Full-length MYDGF accumulated in cells, whereas truncated
MYDGF appeared in the medium. These observations reveal that MYDGF resides in the
ER and Golgi and provide a new framework for investigating and understanding this
intriguing protein.
PMID- 29954951
TI - SGLT2 inhibition and kidney protection.
AB - Type 2 diabetes mellitus (T2DM) is a growing public health concern worldwide.
Numerous drug classes are available for treatment, however, their efficacy with
regard to diabetes-induced renal and cardiovascular (CV) complications remains
limited. Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) are a new class
of blood glucose lowering medications that block renal glucose reabsorption and
have protective effects on the kidney and the heart. This review focusses on the
effects of SGLT2 inhibitors on the kidney and renal outcome: it briefly outlines
renal glucose handling in diabetes and its role in glomerular hyperfiltration and
renal hypoxia; describes how SGLT2 inhibitors induce an early, reversible
reduction in glomerular filtration rate (GFR) and preserve GFR in the long-term
in patients with T2DM; discusses whether the enhanced active transport in the
renal outer medulla (OM) in response to SGLT2 inhibition is friend or foe;
proposes how the blood pressure lowering and heart failure protective effect of
SGLT2 inhibitors can be preserved in chronic kidney disease (CKD) despite
attenuated antihyperglycemic effects; and examines whether SGLT2 inhibition
enhances the incidence or severity of acute kidney injury (AKI).
PMID- 29954952
TI - Cirrhosis regression: extrahepatic angiogenesis and liver hyperarterialization
persist.
AB - Data on the consequences of cirrhosis regression on portal hypertension and on
splanchnic and systemic hemodynamic are scarce. Previous studies have reported a
decrease in hepatic venous pressure gradient following antiviral treatment in
patients with hepatitis B or C related cirrhosis. However, these studies did not
investigate splanchnic and systemic hemodynamic changes associated with virus
control. To fill this gap in knowledge, in a recent issue of Clinical Science,
Hsu et al. (vol. 132, issue 6, 669-683) used rat models of cirrhosis induced by
thioacetamide and by bile duct ligation and provided a comprehensive analysis of
the effects of cirrhosis regression on splanchnic and systemic hemodynamics. They
observed a significant reduction in portal pressure accompanied by a
normalization of systemic hemodynamic (normal cardiac index and systemic vascular
resistance) and a decrease in intrahepatic vascular resistance. No change in
extrahepatic vascular structures were observed despite normalization of
collateral shunting, meaning that portosystemic collaterals persist but are not
perfused. One intriguing part of their results is the only marginal effect of
cirrhosis regression on liver hyperarterialisation. This result suggests that
changes in splanchnic hemodynamic features induced by cirrhosis remain when
hepatic vascular resistance decreases, raising the hypothesis of an autonomous
mechanism persisting despite regression of intrahepatic vascular resistance.
Microbiota changes and bacterial translocation might account for this effect. In
conclusion cirrhosis regression normalizes systemic hemodynamics, but some
splanchnic hemodynamic changes persist including extrahepatic angiogenesis and
liver hyperarterialization.
PMID- 29954949
TI - The S. pombe mitochondrial transcriptome.
AB - Mitochondrial gene expression is largely controlled through post-transcriptional
processes including mitochondrial RNA (mt-RNA) processing, modification, decay,
and quality control. Defective mitochondrial gene expression results in
mitochondrial oxidative phosphorylation (OXPHOS) deficiency and has been
implicated in human disease. To fully understand mitochondrial transcription and
RNA processing, we performed RNA-seq analyses of mt-RNAs from the fission yeast
Schizosaccharomyces pombe RNA-seq analyses show that the abundance of mt-RNAs
vary greatly. Analysis of data also reveals mt-RNA processing sites including an
unusual RNA cleavage event by mitochondrial tRNA (mt-tRNA) 5'-end processing
enzyme RNase P. Additionally, this analysis reveals previously unknown
mitochondrial transcripts including the rnpB-derived fragment, mitochondrial
small RNAs (mitosRNAs) such as mt-tRNA-derived fragments (mt-tRFs) and mt-tRNA
halves, and mt-tRNAs marked with 3'-CCACCA/CCACC in S. pombe Finally, RNA-seq
reveals that inactivation of trz2 encoding S. pombe mitochondrial tRNA 3'-end
processing enzyme globally impairs mt-tRNA 3'-end processing, inhibits mt-mRNA 5'
end processing, and causes accumulation of unprocessed transcripts, demonstrating
the feasibility of using RNA-seq to examine the protein known or predicted to be
involved in mt-RNA processing in S. pombe Our work uncovers the complexity of a
fungal mitochondrial transcriptome and provides a framework for future studies of
mitochondrial gene expression using S. pombe as a model system.
PMID- 29954953
TI - Correction: Biomarkers of disease can be detected in mice as early as 4 weeks
after initiation of exposure to third-hand smoke levels equivalent to those found
in homes of smokers.
PMID- 29954950
TI - Effects of flanking regions on HDV cotranscriptional folding kinetics.
AB - Hepatitis delta virus (HDV) ribozyme performs the self-cleavage activity through
folding to a double pseudoknot structure. The folding of functional RNA
structures is often coupled with the transcription process. In this work, we
developed a new approach for predicting the cotranscriptional folding kinetics of
RNA secondary structures with pseudoknots. We theoretically studied the
cotranscriptional folding behavior of the 99-nucleotide (nt) HDV sequence, two
upstream flanking sequences, and one downstream flanking sequence. During
transcription, the 99-nt HDV can effectively avoid the trap intermediates and
quickly fold to the cleavage-active state. It is different from its refolding
kinetics, which folds into an intermediate trap state. For all the sequences, the
ribozyme regions (from 1 to 73) all fold to the same structure during
transcription. However, the existence of the 30-nt upstream flanking sequence can
inhibit the ribozyme region folding into the active native state through forming
an alternative helix Alt1 with the segments 70-90. The longer upstream flanking
sequence of 54 nt itself forms a stable hairpin structure, which sequesters the
formation of the Alt1 helix and leads to rapid formation of the cleavage-active
structure. Although the 55-nt downstream flanking sequence could invade the
already folded active structure during transcription by forming a more stable
helix with the ribozyme region, the slow transition rate could keep the structure
in the cleavage-active structure to perform the activity.
PMID- 29954956
TI - News at a glance.
PMID- 29954955
TI - Tomorrow's Earth.
PMID- 29954954
TI - Net-zero emissions energy systems.
AB - Some energy services and industrial processes-such as long-distance freight
transport, air travel, highly reliable electricity, and steel and cement
manufacturing-are particularly difficult to provide without adding carbon dioxide
(CO2) to the atmosphere. Rapidly growing demand for these services, combined with
long lead times for technology development and long lifetimes of energy
infrastructure, make decarbonization of these services both essential and urgent.
We examine barriers and opportunities associated with these difficult-to
decarbonize services and processes, including possible technological solutions
and research and development priorities. A range of existing technologies could
meet future demands for these services and processes without net addition of CO2
to the atmosphere, but their use may depend on a combination of cost reductions
via research and innovation, as well as coordinated deployment and integration of
operations across currently discrete energy industries.
PMID- 29954957
TI - Random number generators go public.
PMID- 29954958
TI - In Nigeria, a battle against plagiarism heats up.
PMID- 29954959
TI - Newborn screening urged for fatal neurological disorder.
PMID- 29954960
TI - See-through solar cells could power offices.
PMID- 29954961
TI - Blood test may predict cancer immunotherapy benefit.
PMID- 29954962
TI - The power of many.
PMID- 29954963
TI - Is cancer a breakdown of multicellularity?
PMID- 29954964
TI - Opening the lab door.
PMID- 29954965
TI - Toward a sustainable materials system.
PMID- 29954966
TI - More friction for polyelectrolyte brushes.
PMID- 29954967
TI - Learning from past climatic changes.
PMID- 29954968
TI - Macrophages stimulate mammary stem cells.
PMID- 29954969
TI - Connecting neuronal circuits for movement.
PMID- 29954970
TI - When the cure kills-CBD limits biodiversity research.
PMID- 29954971
TI - Education for the future.
PMID- 29954972
TI - Second Chern number of a quantum-simulated non-Abelian Yang monopole.
AB - Topological order is often quantified in terms of Chern numbers, each of which
classifies a topological singularity. Here, inspired by concepts from high-energy
physics, we use quantum simulation based on the spin degrees of freedom of atomic
Bose-Einstein condensates to characterize a singularity present in five
dimensional non-Abelian gauge theories-a Yang monopole. We quantify the monopole
in terms of Chern numbers measured on enclosing manifolds: Whereas the well-known
first Chern number vanishes, the second Chern number does not. By displacing the
manifold, we induce and observe a topological transition, where the topology of
the manifold changes to a trivial state.
PMID- 29954973
TI - Multivalent counterions diminish the lubricity of polyelectrolyte brushes.
AB - Polyelectrolyte brushes provide wear protection and lubrication in many
technical, medical, physiological, and biological applications. Wear resistance
and low friction are attributed to counterion osmotic pressure and the hydration
layer surrounding the charged polymer segments. However, the presence of
multivalent counterions in solution can strongly affect the interchain
interactions and structural properties of brush layers. We evaluated the
lubrication properties of polystyrene sulfonate brush layers sliding against each
other in aqueous solutions containing increasing concentrations of counterions.
The presence of multivalent ions (Y3+, Ca2+, Ba2+), even at minute
concentrations, markedly increases the friction forces between brush layers owing
to electrostatic bridging and brush collapse. Our results suggest that the
lubricating properties of polyelectrolyte brushes in multivalent solution are
hindered relative to those in monovalent solution.
PMID- 29954974
TI - Carbonyl catalysis enables a biomimetic asymmetric Mannich reaction.
AB - Chiral amines are widely used as catalysts in asymmetric synthesis to activate
carbonyl groups for alpha-functionalization. Carbonyl catalysis reverses that
strategy by using a carbonyl group to activate a primary amine. Inspired by
biological carbonyl catalysis, which is exemplified by reactions of pyridoxal
dependent enzymes, we developed an N-quaternized pyridoxal catalyst for the
asymmetric Mannich reaction of glycinate with aryl N-diphenylphosphinyl imines.
The catalyst exhibits high activity and stereoselectivity, likely enabled by
enzyme-like cooperative bifunctional activation of the substrates. Our work
demonstrates the catalytic utility of the pyridoxal moiety in asymmetric
catalysis.
PMID- 29954975
TI - Enhanced photovoltage for inverted planar heterojunction perovskite solar cells.
AB - The highest power conversion efficiencies (PCEs) reported for perovskite solar
cells (PSCs) with inverted planar structures are still inferior to those of PSCs
with regular structures, mainly because of lower open-circuit voltages (Voc).
Here we report a strategy to reduce nonradiative recombination for the inverted
devices, based on a simple solution-processed secondary growth technique. This
approach produces a wider bandgap top layer and a more n-type perovskite film,
which mitigates nonradiative recombination, leading to an increase in Voc by up
to 100 millivolts. We achieved a high Voc of 1.21 volts without sacrificing
photocurrent, corresponding to a voltage deficit of 0.41 volts at a bandgap of
1.62 electron volts. This improvement led to a stabilized power output
approaching 21% at the maximum power point.
PMID- 29954976
TI - A method for single-neuron chronic recording from the retina in awake mice.
AB - The retina, which processes visual information and sends it to the brain, is an
excellent model for studying neural circuitry. It has been probed extensively ex
vivo but has been refractory to chronic in vivo electrophysiology. We report a
nonsurgical method to achieve chronically stable in vivo recordings from single
retinal ganglion cells (RGCs) in awake mice. We developed a noncoaxial
intravitreal injection scheme in which injected mesh electronics unrolls inside
the eye and conformally coats the highly curved retina without compromising
normal eye functions. The method allows 16-channel recordings from multiple types
of RGCs with stable responses to visual stimuli for at least 2 weeks, and reveals
circadian rhythms in RGC responses over multiple day/night cycles.
PMID- 29954977
TI - Heterogeneous to homogeneous melting transition visualized with ultrafast
electron diffraction.
AB - The ultrafast laser excitation of matters leads to nonequilibrium states with
complex solid-liquid phase-transition dynamics. We used electron diffraction at
mega-electron volt energies to visualize the ultrafast melting of gold on the
atomic scale length. For energy densities approaching the irreversible melting
regime, we first observed heterogeneous melting on time scales of 100 to 1000
picoseconds, transitioning to homogeneous melting that occurs catastrophically
within 10 to 20 picoseconds at higher energy densities. We showed evidence for
the heterogeneous coexistence of solid and liquid. We determined the ion and
electron temperature evolution and found superheated conditions. Our results
constrain the electron-ion coupling rate, determine the Debye temperature, and
reveal the melting sensitivity to nucleation seeds.
PMID- 29954978
TI - Two-channel model for ultralow thermal conductivity of crystalline Tl3VSe4.
AB - Solids with ultralow thermal conductivity are of great interest as thermal
barrier coatings for insulation or thermoelectrics for energy conversion.
However, the theoretical limits of lattice thermal conductivity (kappa) are
unclear. In typical crystals a phonon picture is valid, whereas lowest kappa
values occur in highly disordered materials where this picture fails and heat is
supposedly carried by random walk among uncorrelated oscillators. Here we
identify a simple crystal, Tl3VSe4, with a calculated phonon kappa [0.16 Watts
per meter-Kelvin (W/m-K)] one-half that of our measured kappa (0.30 W/m-K) at 300
K, approaching disorder kappa values, although Raman spectra, specific heat, and
temperature dependence of kappa reveal typical phonon characteristics. Adding a
transport component based on uncorrelated oscillators explains the measured kappa
and suggests that a two-channel model is necessary for crystals with ultralow
kappa.
PMID- 29954979
TI - The plateau of human mortality: Demography of longevity pioneers.
AB - Theories about biological limits to life span and evolutionary shaping of human
longevity depend on facts about mortality at extreme ages, but these facts have
remained a matter of debate. Do hazard curves typically level out into high
plateaus eventually, as seen in other species, or do exponential increases
persist? In this study, we estimated hazard rates from data on all inhabitants of
Italy aged 105 and older between 2009 and 2015 (born 1896-1910), a total of 3836
documented cases. We observed level hazard curves, which were essentially
constant beyond age 105. Our estimates are free from artifacts of aggregation
that limited earlier studies and provide the best evidence to date for the
existence of extreme-age mortality plateaus in humans.
PMID- 29954980
TI - Predictive modeling of U.S. health care spending in late life.
AB - That one-quarter of Medicare spending in the United States occurs in the last
year of life is commonly interpreted as waste. But this interpretation presumes
knowledge of who will die and when. Here we analyze how spending is distributed
by predicted mortality, based on a machine-learning model of annual mortality
risk built using Medicare claims. Death is highly unpredictable. Less than 5% of
spending is accounted for by individuals with predicted mortality above 50%. The
simple fact that we spend more on the sick-both on those who recover and those
who die-accounts for 30 to 50% of the concentration of spending on the dead. Our
results suggest that spending on the ex post dead does not necessarily mean that
we spend on the ex ante "hopeless."
PMID- 29954982
TI - The cost of a career.
PMID- 29954981
TI - Prevalence-induced concept change in human judgment.
AB - Why do some social problems seem so intractable? In a series of experiments, we
show that people often respond to decreases in the prevalence of a stimulus by
expanding their concept of it. When blue dots became rare, participants began to
see purple dots as blue; when threatening faces became rare, participants began
to see neutral faces as threatening; and when unethical requests became rare,
participants began to see innocuous requests as unethical. This "prevalence
induced concept change" occurred even when participants were forewarned about it
and even when they were instructed and paid to resist it. Social problems may
seem intractable in part because reductions in their prevalence lead people to
see more of them.
PMID- 29954983
TI - Correction: Pressure of academic publishing for medical students: a student's
perspective.
PMID- 29954984
TI - The peculiar health beliefs of the Nacirema.
PMID- 29954985
TI - Global extent of rivers and streams.
AB - The turbulent surfaces of rivers and streams are natural hotspots of
biogeochemical exchange with the atmosphere. At the global scale, the total river
atmosphere flux of trace gasses such as carbon dioxide depends on the proportion
of Earth's surface that is covered by the fluvial network, yet the total surface
area of rivers and streams is poorly constrained. We used a global database of
planform river hydromorphology and a statistical approach to show that global
river and stream surface area at mean annual discharge is 773,000 +/- 79,000
square kilometers (0.58 +/- 0.06%) of Earth's nonglaciated land surface, an area
44 +/- 15% larger than previous spatial estimates. We found that rivers and
streams likely play a greater role in controlling land-atmosphere fluxes than is
currently represented in global carbon budgets.
PMID- 29954986
TI - Structural basis for the recognition of Sonic Hedgehog by human Patched1.
AB - The Hedgehog (Hh) pathway involved in development and regeneration is activated
by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We
report the structures of human Ptch1 alone and in complex with the N-terminal
domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 and 3.6 angstroms,
respectively, as determined by cryo-electron microscopy. Ptch1 comprises two
interacting extracellular domains, ECD1 and ECD2, and 12 transmembrane segments
(TMs), with TMs 2 to 6 constituting the sterol-sensing domain (SSD). Two steroid
shaped densities are resolved in both structures, one enclosed by ECD1/2 and the
other in the membrane-facing cavity of the SSD. Structure-guided mutational
analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. The
structure of a steroid binding-deficient Ptch1 mutant displays pronounced
conformational rearrangements.
PMID- 29954987
TI - Dirac electrons in a dodecagonal graphene quasicrystal.
AB - Quantum states of quasiparticles in solids are dictated by symmetry. We have
experimentally demonstrated quantum states of Dirac electrons in a two
dimensional quasicrystal without translational symmetry. A dodecagonal
quasicrystalline order was realized by epitaxial growth of twisted bilayer
graphene rotated exactly 30 degrees . We grew the graphene quasicrystal up to a
millimeter scale on a silicon carbide surface while maintaining the single
rotation angle over an entire sample and successfully isolated the quasicrystal
from a substrate, demonstrating its structural and chemical stability under
ambient conditions. Multiple Dirac cones replicated with the 12-fold rotational
symmetry were observed in angle-resolved photoemission spectra, which revealed
anomalous strong interlayer coupling with quasi-periodicity. Our study provides a
way to explore physical properties of relativistic fermions with controllable
quasicrystalline orders.
PMID- 29954989
TI - Emergence of coexisting ordered states in active matter systems.
AB - Active systems can produce a far greater variety of ordered patterns than
conventional equilibrium systems. In particular, transitions between disorder and
either polar- or nematically ordered phases have been predicted and observed in
two-dimensional active systems. However, coexistence between phases of different
types of order has not been reported. We demonstrate the emergence of dynamic
coexistence of ordered states with fluctuating nematic and polar symmetry in an
actomyosin motility assay. Combining experiments with agent-based simulations, we
identify sufficiently weak interactions that lack a clear alignment symmetry as a
prerequisite for coexistence. Thus, the symmetry of macroscopic order becomes an
emergent and dynamic property of the active system. These results provide a
pathway by which living systems can express different types of order by using
identical building blocks.
PMID- 29954988
TI - Cryo-EM structure of a mitochondrial calcium uniporter.
AB - Calcium transport plays an important role in regulating mitochondrial physiology
and pathophysiology. The mitochondrial calcium uniporter (MCU) is a calcium
selective ion channel that is the primary mediator for calcium uptake into the
mitochondrial matrix. Here, we present the cryo-electron microscopy structure of
the full-length MCU from Neurospora crassa to an overall resolution of ~3.7
angstroms. Our structure reveals a tetrameric architecture, with the soluble and
transmembrane domains adopting different symmetric arrangements within the
channel. The conserved W-D-Phi-Phi-E-P-V-T-Y sequence motif of MCU pore forms a
selectivity filter comprising two acidic rings separated by one helical turn
along the central axis of the channel pore. The structure combined with
mutagenesis gives insight into the basis of calcium recognition.
PMID- 29954990
TI - Rise of the titans.
PMID- 29954991
TI - 'Tax pharma companies if they fail to act on AMR', says Review chief Lord
O'Neill.
PMID- 29954993
TI - Gove under fire for qualifications' remarks.
PMID- 29954994
TI - Do UK vets need an ethical code of practice?
PMID- 29954998
TI - A milestone towards eliminating rabies.
AB - Mission Rabies has announced that it has educated one million primary school
children in Malawi about the dangers of rabies. Juliette Mouezy reports.
PMID- 29955004
TI - Medicines update.
PMID- 29955005
TI - No news is still good news: well-conducted studies with negative results make for
a stronger evidence base.
PMID- 29955007
TI - Evaluating badger culling policy.
PMID- 29955008
TI - Equine lower airway disease.
PMID- 29955009
TI - Rabbit care.
PMID- 29955010
TI - Sudden deaths in greyhounds due to canine haemorrhagic pneumonia.
PMID- 29955011
TI - Correlation between health and welfare.
PMID- 29955012
TI - Correlation between health and welfare.
PMID- 29955013
TI - Dogs and car boots.
PMID- 29955014
TI - Rabbit medicine CPD.
PMID- 29955015
TI - Rabbit care.
PMID- 29955016
TI - The challenge of 10-minute appointments.
PMID- 29955019
TI - To Understand the Modulatory Effect of Probiotics on Irritable Bowel Syndrome.
PMID- 29955020
TI - Bronchoscopy Using Virtual Navigation and Endobronchial Ultrasonography with a
Guide Sheath (EBUS-GS) with or without Fluoroscopy for Peripheral Pulmonary
Lesions.
AB - OBJECTIVE: Endobronchial ultrasonography and guide sheath (EBUS-GS) technique has
high diagnostic yield in lung nodules. Virtual bronchoscopic navigation (VBN) can
lead bronchoscope to the target bronchi. The aim of this prospective study was to
compare the diagnostic yield of two bronchoscopic procedures: bronchoscopy under
EBUS-GS and VBN with or without x-ray fluoroscopy in small peripheral pulmonary
lesions (PPLs, <=30mm) with apparent CT-bronchus sign. METHODS: 31 patients with
PPLs which had apparent CT-bronchus sign were randomly assigned to the X-ray or
the non-X-ray groups (18 with and 13 without fluoroscopy) between September 1,
2012, and September 30, 2015. A bronchoscope was introduced into the target
bronchus using the VBN system. Sites of specimen sampling were verified using
EBUS-GS with or without fluoroscopy. RESULTS: The overall diagnostic yield was
83.3% in the X-ray and 69.2% in the non-X-ray group. The diagnostic yield of
malignancy was 88.2% and 81.8%, respectively. The duration of the examination and
time elapsed until the first EBUS visualization were similar in the X-ray and the
non-X-ray group (9.0 (5.8-20.) min vs 11.0 (5.3-17.3) min, and 2.5 (1.3-14.2) min
vs 4.1 (1.4-8.1) min, respectively). The fluoroscopy exposure time was 3.7 (2.9
10.56) min. The only adverse event was mild pneumothorax in a patient from the
non-X-ray group, who had consequent TBB under fluoroscopy. CONCLUSIONS: There was
a possibility that VBN-guided EBUS-transbronchial diagnosis without fluoroscopy
might be equivalent to that under fluoroscopy. Further multi-center randomized
study may be desired. (UMIN000008592).
PMID- 29955021
TI - Nontypeable Haemophilus Influenzae Sepsis in a Term Neonate.
AB - We reported a term newborn case of early onset sepsis caused by nontypeable
Haemophilus Influenzae (NTHi) with massive bacterial invasion in the placenta.
Based on the consistent results of maternal placental pathology and neonatal
bacterial culture, we diagnosed this as vertical transmission of NTHi via vaginal
delivery. In general, NTHi infections occur in preterm infants, and our term
infant case is very unusual. In conclusion, clinicians should consider NTHi as a
cause of neonatal sepsis, even in term infants.
PMID- 29955022
TI - A Case of Congenital Complete Atrioventricular Block Treated with Transdermal
Tulobuterol.
AB - Congenital complete atrioventricular block (CCAVB) is a condition in which the
atria and ventricles beat independently of each other. CCAVB cases require
permanent pacemaker implantation until adulthood. Nevertheless, consensus
regarding postnatal medical therapy for bradycardia has not been reached. Here we
report the case of a newborn with CCAVB, whose intractable bradycardia was
successfully treated with transdermal tulobuterol. Tulobuterol is a selective
beta2-adrenoceptor agonist, widely used safely as bronchodilator in children. It
also has positive inotropic and chronotropic effect via beta1-adrenoceptors. We
believe the tulobuterol patch can be used as an optional therapy for CCAVB where
pacemaker implantation is not available.
PMID- 29955023
TI - Modified TALK Score for Japanese Patients with Laryngeal and Hypopharyngeal
Cancers to Predict the Possibility of Laryngeal Preservation by Concurrent
Chemoradiotherapy.
AB - OBJECTIVE: TALK score has been developed as an index for predicting the
possibility of larynx preservation and prognosis of the patients with advanced
laryngeal and hypopharyngeal cancers treated by concurrent chemoradiotherapy
(CCRT). In this study, we validated the original TALK score in our clinical
setting and modified the score for Japanese population. METHODS: The subjects
were 21 patients with laryngeal cancer and 50 patients with hypopharyngeal cancer
who underwent CCRT at Kobe University Hospital between April 2007 and August
2012. Data regarding T stage, serum albumin level just before treatment, maximum
alcohol use, Karnofsky Performance Status (KPS), 3-year overall survival rate and
3-year larynx-preservation rate were collected from medical records. In the
revised TALK score (JTALK), the following scoring criteria were modified to
adjust Japanese population: T stage of the primary tumor (>=T3), serum albumin
level (<3.5 g/dl), maximum alcohol use (>=one 350-ml can of beer/day or an
equivalent amount), and KPS (<80%). RESULTS: The original TALK score was not
significantly associated with the larynx preservation rates or survival rates for
laryngeal cancer or hypopharyngeal cancer. Instead, JTALK score was significantly
associated with the 3-year larynx preservation rates and 3-year survival rates of
the patients with hypopharyngeal and laryngeal cancer. CONCLUSION: These results
indicate that JTALK score could be a useful index for predicting the possibility
of larynx preservation and prognosis of Japanese patients with advanced laryngeal
and hypopharyngeal cancer treated by CCRT.
PMID- 29955024
TI - Essential Role of Sphingosine Kinase 2 in the Regulation of Cargo Contents in the
Exosomes from K562 Cells.
AB - Sphingosine 1-phosphate (S1P) is a bioactive phosphorylated product of
sphingosine catalyzed by sphingosine kinase (SphK) and implicated in diverse
cellular functions including vesicular trafficking. In the present study we have
shown the importance of one of the subtypes of SphK, SphK2, in the regulation of
cargo content in exosomes released from human myeloid leukemia K562 cells. First,
SphK2 has been shown to localize with N-Rh-PE-positive late endosomes in the
cells. Next, siRNA-mediated knockdown of Sphk2 but not SphK1 resulted in a
reduction of cargo content in purified exosomes. The involvement of SphK2 in this
phenomenon was further investigated by pharmacological approaches. When cells
were treated with N,N-dimethylsphingosine (DMS), one of the most frequently used
inhibitors for SphK, cargo contents in purified exosomes were enhanced
unexpectedly. Finally, it has been shown that DMS has a potency to stimulate
SphK2 activity depending on the substrate sphingosine- and the inhibitor-doses as
estimated by in vitro assay systems using a purified SphK2. These findings
suggest that SphK2/S1P signaling plays an important role in the regulation of
cargo content in exosomes in K562 cells.
PMID- 29955025
TI - Maternal gene Ooep may participate in homologous recombination-mediated DNA
double-strand break repair in mouse oocytes.
AB - DNA damage in oocytes can cause infertility and birth defects. DNA double-strand
breaks (DSBs) are highly deleterious and can substantially impair genome
integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant
roles in safeguarding oocyte quantity and quality. However, little is known
regarding the key players of the HR repair pathway in oocytes. Here, we
identified oocyte-specific gene Ooep as a novel key component of the HR repair
pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia
mutated (ATM) kinase activation and Rad51 recombinase(RAD51)focal accumulation at
DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to
apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes
exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving
oocyte quantity and quality by maintaining genome stability. Ooep expression
decreased with the advance of maternal age, suggesting its involvement in
maternal aging.
PMID- 29955026
TI - How many species of Apodemus and Rattus occur in China? A survey based on
mitochondrial cyt b and morphological analyses.
AB - Apodemus (mice) and Rattus (rats) are the top rodent reservoirs for zoonoses in
China, yet little is known about their diversity. We reexamined the alpha
diversity of these two genera based on a new collection of specimens from China
and their cyt b sequences in GenBank. We also tested whether species could be
identified using external and craniodental measurements exclusively. Measurements
from 147 specimens of Apodemus and 236 specimens of Rattus were used for
morphological comparisons. We analysed 74 cyt b sequences of Apodemus and 100 cyt
b sequences of Rattus to facilitate phylogenetic estimations. Results
demonstrated that nine species of Apodemus and seven species of Rattus, plus a
new subspecies of Rattus nitidus, are distributed in China. Principal component
analysis using external and craniodental measurements revealed that measurements
alone could not separate the recognized species. The occurrence of Rattus
pyctoris in China remains uncertain.
PMID- 29955028
TI - Rhinogobius immaculatus, a new species of freshwater goby (Teleostei: Gobiidae)
from the Qiantang River, China.
AB - A new freshwater goby, Rhinogobius immaculatus sp. nov., is described here from
the Qiantang River in China. It is distinguished from all congeners by the
following combination of characters: second dorsal-fin rays I, 7-9; anal-fin rays
I, 6-8; pectoral-fin rays 14-15; longitudinal scales 29-31; transverse scales 7
9; predorsal scales 2-5; vertebrae 27 (rarely 28); preopercular canal absent or
with two pores; a red oblique stripe below eye in males; branchiostegal membrane
mostly reddish-orange, with 3-6 irregular discrete or connected red blotches on
posterior branchiostegal membrane and lower operculum in males; caudal-fin base
with a median black spot; and no black blotch on anterior part of first dorsal
fin in males.
PMID- 29955027
TI - Genomic and transcriptomic analyses reveal selection of genes for puberty in Bama
Xiang pigs.
AB - The Bama Xiang pig (BMX) is a famous early-maturing Chinese indigenous breed with
a two-end black coat. To uncover the genetic basis of the BMX phenotype, we
conducted comparative genomic analyses between BMX and East Asian wild boars and
Laiwu pigs, respectively. Genes under positive selection were enriched in
pathways associated with gonadal hormone and melanin synthesis, consistent with
the phenotypic changes observed during development in BMX pigs. We also performed
differentially expressed gene analysis based on RNA-seq data from pituitary
tissues of BMX and Large White pigs. The CTTNBP2NL, FRS2, KANK4, and KATNAL1
genes were under selection and exhibited expressional changes in the pituitary
tissue, which may affect BMX pig puberty. Our study demonstrated the positive
selection of early maturity in the development of BMX pigs and advances our
knowledge on the role of regulatory elements in puberty evolution in pigs.
PMID- 29955029
TI - Interchange between grooming and infant handling in female Tibetan macaques
(Macaca thibetana).
AB - In some nonhuman primates, infants function as a social tool that can bridge
relationships among group members. Infants are a desired commodity for group
members, and mothers control access to them. The biological market theory
suggests that grooming is widespread and represents a commodity that can be
exchanged for infant handling. As a limited resource, however, the extent to
which infants are interchanged between mothers (females with an infant) and non
mothers (potential handlers, females without an infant) remains unclear. In this
study, we collected behavioral data to investigate the relationship between
grooming and infant handling in free-ranging Tibetan macaques (Macaca thibetana)
at Mt. Huangshan, China. Our results showed that females with infants received
more grooming than females without infants. After her infant was handled, mother
females received more grooming than they did during daily grooming interactions.
However, with the increasing number of infants within the social group, both the
grooming that mothers received and the grooming that non-mothers invested for
handling infants decreased. We also found that non-mothers invested more time in
grooming to gain access to younger infants than older infants. Our results
provide evidence that infants are social commodities for both mother and non
mother females. Mothers use infants for obtain grooming and non-mothers use
grooming to gain access to infants. The current study implies a bidirectional and
complex interchange pattern between grooming and infant handling to compensate
for the dyadic grooming disparity in non-human primates.
PMID- 29955030
TI - Home range variation of two different-sized groups of golden snub-nosed monkeys
(Rhinopithecus roxellana) in Shennongjia, China: implications for feeding
competition.
AB - Knowledge on the home range size of a species or population is important for
understanding its behavioral and social ecology and improving the effectiveness
of conservation strategies. We studied the home range size of two different-sized
groups of golden snub-nosed monkeys (Rhinopithecus roxellana) in Shennongjia,
China. The larger group (236 individuals) had a home range of 22.5 km2 from
September 2007 to July 2008, whereas the smaller group (62 individuals) occupied
a home range of 12.4 km2 from November 2008 to July 2009. Both groups exhibited
considerable seasonal variation in their home range size, which was likely due to
seasonal changes in food availability and distribution. The home range in any
given season (winter, spring, summer, or winter+spring+summer) of the larger
group was larger than that of the smaller group. As the two groups were studied
in the same area, with the confounding effects of food availability thus
minimized, the positive relationship between home range size and group size
suggested that scramble feeding competition increased within the larger group.
PMID- 29955031
TI - Peritoneal Myeloid Sarcoma in a Patient Treated for a Testicular Seminoma.
AB - BACKGROUND Myeloid sarcoma is a rare extramedullary soft tissue neoplasm composed
of myeloblastic cells, usually associated to hematologic tumor disorders and a
poor prognosis. Its diagnosis is very difficult as radiological images are not
specific. Histology and immunohistochemistry are necessary for an accurate
diagnosis. CASE REPORT We report the case of 46-year-old, Caucasian, non-smoker
male, treated in 2014 by orchiectomy and systemic chemotherapy for a stage IIB
testicular seminoma. Considering the rapid increase of lactate dehydrogenase
(LDH) levels without any evident medical reason, a computed tomography/positron
emission tomography (CT/PET) scan was performed and revealing a diffuse, nodular,
peritoneal tumor infiltration associated with multiple mesenteric and mediastinal
adenopathies. Laparoscopy confirmed a diffuse tumor infiltration of the
peritoneum. Histology and immunohistochemistry were consisted with the diagnosis
of a myeloid monoblastic sarcoma. Cytology of bone marrow documented an monocytic
acute myeloid leukemia. The patient started a systemic induction chemotherapy
with high dose cytarabine and idarubicin that was complicated by an infectious
pneumonia and colitis, and a grade IV thrombocytopenia leading to a brain
subdural hemorrhage and quickly to patient's death. CONCLUSIONS We describe a
rare, peritoneal, myeloid sarcoma in a young patient who had been treated by
systemic chemotherapy for testicular seminoma 4 years earlier. The patient was
clinically asymptomatic and presented only elevated LDH levels without any
evident clinical reason. Considering the persistence of this biochemical
abnormality, more investigations were performed leading to a diagnosis of
peritoneal myeloid sarcoma associated with monocytic acute myeloid leukemia,
probably secondary to the past chemotherapy.
PMID- 29955032
TI - Anti-Inflammatory Effect of Atorvastatin on the Kidney Graft of Living Donor
Transplants.
AB - BACKGROUND Recent studies have demonstrated that statins have anti-inflammatory
and immunomodulatory properties, which could be considered beneficial in kidney
transplantations. This study assesses the anti-inflammatory effect of
atorvastatin on the kidney grafts of living donor transplants. MATERIAL AND
METHODS In a randomized clinical trial, kidney donors were divided into 2 groups.
The study group constituted 24 donors who received 40 mg atorvastatin, and 24
donors who received a placebo control, 4 weeks prior to transplantation. Serum C
reactive protein (CRP) levels were measured before and after atorvastatin
administration. CRP and renal function of kidney recipients were measured at
baseline and 1, 6, and 24 hours after transplantation. RESULTS After 4 weeks of
treatment, the CRP level was 5.62+/-3.82 mg/dL in the control group and 3.27+/
0.62 mg/dL in the study group (P=0.007). Upon reperfusion, CRP levels in
recipients at 1 hour were, 5.8+/-3.9 and 3.8+/-1.0 mg/dL, respectively (P=0.04).
Twenty-four hours after the kidney transplantations, serum creatinine levels were
2.5+/-1.5 mg/dL in the study group and 3.7+/-2.4 mg/dL in the control group
(P=0.04). CONCLUSIONS Our study suggests that the use of atorvastatin prior to
allograft procurement of kidney transplant, reduces the acute kidney inflammatory
burden profile, and promotes an improved kidney function recovery following
transplantation.
PMID- 29955033
TI - Therapeutic Antidepressant Potential of NONHSAG045500 in Regulating Serotonin
Transporter in Major Depressive Disorder.
AB - BACKGROUND Major depressive disorder (MDD) is a chronic, life-threatening, highly
disabling disease. Standardized treatment with fewer adverse effects, quick
onset, and long-term maintenance of the effects of brief treatment for MDD is
always being pursued. Long non-coding RNAs (lncRNAs) are highly expressed in the
central nervous system and are involved in the occurrence and development of
neurodegenerative and psychiatric diseases. This study aimed to investigate
whether the overexpression and interference of 3 differentially down-regulated
lncRNAs (NONHSAT142707, NONHSAG045500, and ENST00000517573) in MDD can affect the
expression of central neurotransmitter serotonin (5-hydroxytryptamine)
transporter (SERT) in vitro. MATERIAL AND METHODS First, we synthesized and
validated the effect of 3 lncRNA plasmids and small interfering RNAs (siRNAs);
next, we transfected the plasmids and siRNAs that caused significant
overexpression or interference in SK-N-SH cells, and tested the expression of
SERT by qRT-PCR. RESULTS The results showed that 3 lncRNA plasmids and siRNAs2
caused overexpression and interference, respectively. Only the overexpression of
NONHSAG045500 could significantly inhibit the expression of SERT; interference
with NONHSAG045500 could significantly strengthen the expression of SERT.
CONCLUSIONS This study indicated that the expression of SERT could be regulated
by up-regulating or down-regulating NONHSAG045500 expression and suggested that
NONHSAG045500 could potentially be established as a new therapeutic target of
MDD. Future work may be needed to definitively determine the correlation between
NONHSAG045500 and SERT in vivo.
PMID- 29955034
TI - Development and validation of a new rating scale for perimenopausal depression
the Meno-D.
AB - The menopause transition is a time when women experience an increased risk for
new onset depression, as well as relapse of depression. While there are
overlapping symptoms between major depression and depression during menopause,
differences suggest 'perimenopausal depression' may be a unique subtype of
depression associated with characteristic symptoms. There is currently no
validated scale designed to measure perimenopausal depression. The aim of the
current study was to develop and validate the 'Meno-D', a self-reporting or
clinician rated questionnaire, designed to rate the severity of symptoms of
perimenopausal depression. The development phase of the Meno-D involved
literature review, clinical observation, and focus groups. A 12-item
questionnaire was developed and clinically reviewed for face validity for
content. The Meno-D was administered to women experiencing symptoms of
perimenopausal depression as part of a larger baseline assessment battery.
Validation involved confirmatory factor analysis (CFA). The development of the
Meno-D resulted in 12 items. A total of 93 participants with perimenopausal
depression were involved in the baseline assessments, 82 completed the Meno-D.
Factor analysis identified five sub-scales of the Meno-D "somatic; cognitive;
self; sleep; sexual" with high-internal consistency; discriminant validity and a
good construct and convergent validity. The Meno-D provides a unique tool for
clinicians and researchers to measure the presence of perimenopausal depression.
PMID- 29955035
TI - Identification of strong intron enhancer in the heparanase gene: effect of
functional rs4693608 variant on HPSE enhancer activity in hematological and solid
malignancies.
AB - Heparanase is an endo-beta-glucuronidase that specifically cleaves the saccharide
chains of heparan sulfate (HS) proteoglycans and releases HS-bound cytokines,
chemokines, and bioactive growth-promoting factors. Heparanase plays an important
role in the nucleus as part of an active chromatin complex. Our previous studies
revealed that rs4693608 correlates with heparanase levels and increased risk of
acute and extensive chronic graft vs. host disease (GVHD). Discrepancy between
recipient and donor in this SNP significantly affected the risk of acute GVHD. In
the present study, we analyzed the HPSE gene region, including rs4693608, and
demonstrated that this region exhibits SNPs-dependent enhancer activity. Analysis
of nuclear proteins from normal leukocytes revealed their binding to DNA probe of
both alleles with higher affinity to allele G. All malignant cell lines and
leukemia samples disclosed a shift of the main bands in comparison to normal
leukocytes. At least five additional shifted bands were bound to allele A while
allele G probe was bound to only one main DNA/protein complex. Additional SNPs
rs4693083, rs4693084, and rs4693609 were found in strong linkage disequilibrium
(LD) with rs11099592 (exon 7). Only rs4693084 affected protein binding to DNA in
cell lines and leukemia samples. As a result of the short distance between
rs4693608 and rs4693084, both SNPs may be included in a common DNA/protein
complex. DNA pull-down assay revealed that heparanase is involved in self
regulation by negative feedback in rs4693608-dependent manner. During
carcinogenesis, heparanase self-regulation is discontinued and the helicase-like
transcription factor begins to regulate this enhancer region. Altogether, our
study elucidates conceivable mechanism(s) by which rs4693608 SNP regulates HPSE
gene expression and the associated disease outcome.
PMID- 29955036
TI - Bile acid metabolism and signaling: potential therapeutic target for nonalcoholic
fatty liver disease.
PMID- 29955037
TI - Global pairwise RNA interaction landscapes reveal core features of protein
recognition.
AB - RNA-protein interactions permeate biology. Transcription, translation, and
splicing all hinge on the recognition of structured RNA elements by RNA-binding
proteins. Models of RNA-protein interactions are generally limited to short
linear motifs and structures because of the vast sequence sampling required to
access longer elements. Here, we develop an integrated approach that calculates
global pairwise interaction scores from in vitro selection and high-throughput
sequencing. We examine four RNA-binding proteins of phage, viral, and human
origin. Our approach reveals regulatory motifs, discriminates between regulated
and non-regulated RNAs within their native genomic context, and correctly
predicts the consequence of mutational events on binding activity. We design
binding elements that improve binding activity in cells and infer mutational
pathways that reveal permissive versus disruptive evolutionary trajectories
between regulated motifs. These coupling landscapes are broadly applicable for
the discovery and characterization of protein-RNA recognition at single
nucleotide resolution.
PMID- 29955038
TI - Glutamate as a potential "survival factor" in an in vitro model of neuronal
hypoxia/reoxygenation injury: leading role of the Na+/Ca2+ exchanger.
AB - In brain ischemia, reduction in oxygen and substrates affects mitochondrial
respiratory chain and aerobic metabolism, culminating in ATP production
impairment, ionic imbalance, and cell death. The restoration of blood flow and
reoxygenation are frequently associated with exacerbation of tissue injury,
giving rise to ischemia/reperfusion (I/R) injury. In this setting, the imbalance
of brain bioenergetics induces important metabolic adaptations, including
utilization of alternative energy sources, such as glutamate. Although glutamate
has long been considered as a neurotoxin, it can also be used as intermediary
metabolite for ATP synthesis, and both the Na+/Ca2+ exchanger (NCX) and the Na+
dependent excitatory amino-acid transporters (EAATs) are essential in this
pathway. Here we analyzed the role of NCX in the potential of glutamate to
improve metabolism and survival of neuronal cells subjected to
hypoxia/reoxygenation (H/R). In SH-SY5Y neuroblastoma cells differentiated into a
neuron-like state, H/R produced a significant cell damage, a decrease in ATP
cellular content, and intracellular Ca2+ alterations. Exposure to glutamate at
the onset of the reoxygenation phase attenuated H/R-induced cell damage and
evoked a significant raise in intracellular ATP levels. Furthermore, we found
that in H/R cells NCX reverse-mode activity was reduced, and that glutamate
limited such reduction. All the effects induced by glutamate supplementation were
lost when cells were transfected with small interfering RNA against NCX1 and
EAAT3, suggesting the need of a specific functional interplay between these
proteins for glutamate-induced protection. Collectively, our results revealed the
potential beneficial effect of glutamate in an in vitro model of H/R injury and
focused on the essential role exerted by NCX1. Although preliminary, these
findings could be a starting point to further investigate in in vivo systems such
protective effect in ischemic settings, shedding a new light on the classical
view of glutamate as detrimental factor.
PMID- 29955039
TI - High-throughput analysis of the RNA-induced silencing complex in myotonic
dystrophy type 1 patients identifies the dysregulation of miR-29c and its target
ASB2.
AB - Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by abnormally
expanded stretches of CTG DNA triplets in the DMPK gene, leading to mutated
transcript RNA-toxicity. MicroRNAs (miRNAs) are short non-coding RNAs that, after
maturation, are loaded onto the RISC effector complex that destabilizes target
mRNAs and represses their translation. In DM1 muscle biopsies not only the
expression, but also the intracellular localization of specific miRNAs is
disrupted, leading to the dysregulation of the relevant mRNA targets. To
investigate the functional alterations of the miRNA/target interactions in DM1,
we analyzed by RNA-sequencing the RISC-associated RNAs in skeletal muscle
biopsies derived from DM1 patients and matched controls. The mRNAs found
deregulated in DM1 biopsies were involved in pathways and functions relevant for
the disease, such as energetic metabolism, calcium signaling, muscle contraction
and p53-dependent apoptosis. Bioinformatic analysis of the miRNA/mRNA
interactions based on the RISC enrichment profiles, identified 24 miRNA/mRNA
correlations. Following validation in 21 independent samples, we focused on the
couple miR-29c/ASB2 because of the role of miR-29c in fibrosis (a feature of late
stage DM1 patients) and of ASB2 in the regulation of muscle mass. Luciferase
reporter assay confirmed the direct interaction between miR-29c and ASB2.
Moreover, decreased miR-29c and increased ASB2 levels were verified also in
immortalized myogenic cells and primary fibroblasts, derived from biopsies of DM1
patients and controls. CRISPR/Cas9-mediated deletion of CTG expansions rescued
normal miR-29c and ASB2 levels, indicating a direct link between the mutant
repeats and the miRNA/target expression. In conclusion, functionally relevant
miRNA/mRNA interactions were identified in skeletal muscles of DM1 patients,
highlighting the dysfunction of miR-29c and ASB2.
PMID- 29955040
TI - Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects
GWAS regions to cardiac gene networks.
AB - Long-range chromosomal interactions bring distal regulatory elements and
promoters together to regulate gene expression in biological processes. By
performing promoter capture Hi-C (PCHi-C) on human embryonic stem cell-derived
cardiomyocytes (hESC-CMs), we show that such promoter interactions are a key
mechanism by which enhancers contact their target genes after hESC-CM
differentiation from hESCs. We also show that the promoter interactome of hESC
CMs is associated with expression quantitative trait loci (eQTLs) in cardiac left
ventricular tissue; captures the dynamic process of genome reorganisation after
hESC-CM differentiation; overlaps genome-wide association study (GWAS) regions
associated with heart rate; and identifies new candidate genes in such regions.
These findings indicate that regulatory elements in hESC-CMs identified by our
approach control gene expression involved in ventricular conduction and rhythm of
the heart. The study of promoter interactions in other hESC-derived cell types
may be of utility in functional investigation of GWAS-associated regions.
PMID- 29955041
TI - Direct evidence for hula twist and single-bond rotation photoproducts.
AB - Photoisomerization reactions are quintessential processes driving molecular
machines and motors, govern smart materials, catalytic processes, and
photopharmacology, and lie at the heart of vision, phototaxis, or vitamin
production. Despite this plethora of applications fundamental photoisomerization
mechanisms are not well understood at present. The famous hula-twist motion-a
coupled single and double-bond rotation-was proposed to explain proficient
photoswitching in restricted environments but fast thermal follow-up reactions
hamper identification of primary photo products. Herein we describe an asymmetric
chromophore possessing four geometrically distinct diastereomeric states that do
not interconvert thermally and can be crystallized separately. Employing this
molecular setup direct and unequivocal evidence for the hula-twist photoreaction
and for photoinduced single-bond rotation is obtained. The influences of the
surrounding medium and temperature are quantified and used to favor unusual
photoreactions. Based on our findings molecular engineers will be able to
implement photo control of complex molecular motions more consciously.
PMID- 29955042
TI - Coherent two-dimensional electronic mass spectrometry.
AB - Coherent two-dimensional (2D) optical spectroscopy has revolutionized our ability
to probe many types of couplings and ultrafast dynamics in complex quantum
systems. The dynamics and function of any quantum system strongly depend on
couplings to the environment. Thus, studying coherent interactions for different
environments remains a topic of tremendous interest. Here we introduce coherent
2D electronic mass spectrometry that allows 2D measurements on effusive molecular
beams and thus on quantum systems with minimum system-bath interaction and employ
this to identify the major ionization pathway of 3d Rydberg states in NO2.
Furthermore, we present 2D spectra of multiphoton ionization, disclosing distinct
differences in the nonlinear response functions leading to the ionization
products. We also realize the equivalent of spectrally resolved transient
absorption measurements without the necessity for acquiring weak absorption
changes. Using time-of-flight detection introduces cations as an observable,
enabling the 2D spectroscopic study on isolated systems of photophysical and
photochemical reactions.
PMID- 29955043
TI - Footprints of parasitism in the genome of the parasitic flowering plant Cuscuta
campestris.
AB - A parasitic lifestyle, where plants procure some or all of their nutrients from
other living plants, has evolved independently in many dicotyledonous plant
families and is a major threat for agriculture globally. Nevertheless, no genome
sequence of a parasitic plant has been reported to date. Here we describe the
genome sequence of the parasitic field dodder, Cuscuta campestris. The genome
contains signatures of a fairly recent whole-genome duplication and lacks genes
for pathways superfluous to a parasitic lifestyle. Specifically, genes needed for
high photosynthetic activity are lost, explaining the low photosynthesis rates
displayed by the parasite. Moreover, several genes involved in nutrient uptake
processes from the soil are lost. On the other hand, evidence for horizontal gene
transfer by way of genomic DNA integration from the parasite's hosts is found. We
conclude that the parasitic lifestyle has left characteristic footprints in the
C. campestris genome.
PMID- 29955045
TI - Astrometrically registered maps of H2O and SiO masers toward VX Sagittarii.
AB - The supergiant VX Sagittarii is a strong emitter of both H2O and SiO masers.
However, previous VLBI observations have been performed separately, which makes
it difficult to spatially trace the outward transfer of the material
consecutively. Here we present the astrometrically registered, simultaneous maps
of 22.2 GHz H2O and 43.1/42.8/86.2/129.3 GHz SiO masers toward VX Sagittarii. The
H2O masers detected above the dust-forming layers have an asymmetric
distribution. The multi-transition SiO masers are nearly circular ring,
suggesting spherically symmetric wind within a few stellar radii. These results
provide the clear evidence that the asymmetry in the outflow is enhanced after
the smaller molecular gas clump transform into the inhomogeneous dust layers. The
129.3 GHz maser arises from the outermost region compared to that of
43.1/42.8/86.2 GHz SiO masers. The ring size of the 129.3 GHz maser is maximized
around the optical maximum, suggesting that radiative pumping is dominant.
PMID- 29955044
TI - Quantitative spatial analysis of haematopoiesis-regulating stromal cells in the
bone marrow microenvironment by 3D microscopy.
AB - Sinusoidal endothelial cells and mesenchymal CXCL12-abundant reticular cells are
principal bone marrow stromal components, which critically modulate
haematopoiesis at various levels, including haematopoietic stem cell maintenance.
These stromal subsets are thought to be scarce and function via highly specific
interactions in anatomically confined niches. Yet, knowledge on their abundance,
global distribution and spatial associations remains limited. Using three
dimensional quantitative microscopy we show that sinusoidal endothelial and
mesenchymal reticular subsets are remarkably more abundant than estimated by
conventional flow cytometry. Moreover, both cell types assemble in topologically
complex networks, associate to extracellular matrix and pervade marrow tissues.
Through spatial statistical methods we challenge previous models and demonstrate
that even in the absence of major specific interaction forces, virtually all
tissue-resident cells are invariably in physical contact with, or close proximity
to, mesenchymal reticular and sinusoidal endothelial cells. We further show that
basic structural features of these stromal components are preserved during
ageing.
PMID- 29955046
TI - Go/No-Go task engagement enhances population representation of target stimuli in
primary auditory cortex.
AB - Primary sensory cortices are classically considered to extract and represent
stimulus features, while association and higher-order areas are thought to carry
information about stimulus meaning. Here we show that this information can in
fact be found in the neuronal population code of the primary auditory cortex
(A1). A1 activity was recorded in awake ferrets while they either passively
listened or actively discriminated stimuli in a range of Go/No-Go paradigms, with
different sounds and reinforcements. Population-level dimensionality reduction
techniques reveal that task engagement induces a shift in stimulus encoding from
a sensory to a behaviorally driven representation that specifically enhances the
target stimulus in all paradigms. This shift partly relies on task-engagement
induced changes in spontaneous activity. Altogether, we show that A1 population
activity bears strong similarities to frontal cortex responses. These findings
indicate that primary sensory cortices implement a crucial change in the
structure of population activity to extract task-relevant information during
behavior.
PMID- 29955048
TI - A model for super El Ninos.
AB - Super El Ninos, the strongest and most powerful of El Ninos, impact economies,
societies, and ecosystems disproportionately. Despite their importance, we do not
fully understand how super El Ninos develop their intensity and unique
characteristics. Here, combining observational analyses with simple numerical
simulations, we suggest that eastern Pacific intensified super El Ninos result
from the interaction of an El Nino and a positive Indian Ocean Dipole. Further,
we identify a self-limiting behavior inherent to El Nino Southern Oscillation
(ENSO) dynamics. This behavior-a consequence of the atmospheric Kelvin wave
response that develops to the east of ENSO's convective anomalies-dampens sea
surface temperature (SST) variations in the eastern Pacific, thereby preventing
super El Ninos from developing through tropical Pacific dynamics alone. Our model
explains the features of the large 1972, 1982, and 1997 El Ninos; the large SST
anomalies during the 2015 El Nino, however, were likely enhanced by strong
decadal variability.
PMID- 29955047
TI - Epidermal-specific deletion of TC-PTP promotes UVB-induced epidermal cell
survival through the regulation of Flk-1/JNK signaling.
AB - UVB exposure can contribute to the development of skin cancer by modulating
protein tyrosine kinase (PTK) signaling. It has been suggested that UVB radiation
increases the ligand-dependent activation of PTKs and induces PTP inactivation.
Our recent studies have shown that T-cell protein tyrosine phosphatase (TC-PTP)
attenuates skin carcinogenesis induced by chemical regimens, which indicates its
critical role in the prevention of skin cancer. In the current work, we report
that TC-PTP increases keratinocyte susceptibility to UVB-induced apoptosis via
the downregulation of Flk-1/JNK signaling. We showed that loss of TC-PTP led to
resistance to UVB-induced apoptosis in vivo epidermis. We established
immortalized primary keratinocytes (IPKs) from epidermal-specific TC-PTP
deficient (K14Cre.Ptpn2fl/fl) mice. Immortalized TC-PTP-deficient keratinocytes
(TC-PTP/KO IPKs) showed increased cell survival against UVB-induced apoptosis
which was concomitant with a UVB-mediated increase in Flk-1 phosphorylation,
especially on tyrosine residue 1173. Inhibition of Flk-1 by either its specific
inhibitors or siRNA in TC-PTP/KO IPKs reversed this effect and significantly
increased cell death after UVB irradiation in comparison with untreated TC-PTP/KO
IPKs. Immunoprecipitation analysis using the TC-PTP substrate-trapping mutant
TCPTP-D182A indicated that TC-PTP directly interacts with Flk-1 to
dephosphorylate it and their interaction was stimulated by UVB. Following UVB
mediated Flk-1 activation, the level of JNK phosphorylation was also
significantly increased in TC-PTP/KO IPKs compared to control IPKs. Similar to
our results with Flk-1, treatment of TC-PTP/KO IPKs with the JNK inhibitor
SP600125 significantly increased apoptosis after UVB irradiation, confirming that
the effect of TC-PTP on UVB-mediated apoptosis is regulated by Flk-1/JNK
signaling. Western blot analysis showed that both phosphorylated Flk-1 and
phosphorylated JNK were significantly increased in the epidermis of TC-PTP
deficient mice compared to control mice following UVB. Our results suggest that
TC-PTP plays a protective role against UVB-induced keratinocyte cell damage by
promoting apoptosis via negative regulation of Flk-1/JNK survival signaling.
PMID- 29955049
TI - Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell
production in the aorta.
AB - Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE)
cells via the formation of intra-aortic haematopoietic clusters (IAHCs) in
vertebrate embryos. The molecular events controlling endothelial specification,
endothelial-to-haematopoietic transition (EHT) and IAHC formation, as it occurs
in vivo inside the aorta, are still poorly understood. To gain insight in these
processes, we performed single-cell RNA-sequencing of non-HE cells, HE cells,
cells undergoing EHT, IAHC cells, and whole IAHCs isolated from mouse embryo
aortas. Our analysis identified the genes and transcription factor networks
activated during the endothelial-to-haematopoietic switch and IAHC cell
maturation toward an HSC fate. Our study provides an unprecedented complete
resource to study in depth HSC generation in vivo. It will pave the way for
improving HSC production in vitro to address the growing need for tailor-made
HSCs to treat patients with blood-related disorders.
PMID- 29955050
TI - Parkin regulates NF-kappaB by mediating site-specific ubiquitination of RIPK1.
AB - Parkin (Park2), a RING-between-RING-type E3 ubiquitin ligase, has been implicated
in regulating NF-kappaB. Mutations in Parkin are associated with Parkinson's
disease. Here we investigated the interaction of Parkin with Receptor-interacting
protein kinase 1 (RIPK1) kinase, a key mediator of multiple signaling pathways
activated by TNFR1 including NF-kappaB pathway. We report that Parkin interacts
with RIPK1 and mediates K63 ubiquitination of RIPK1 on K376 in TNFR1-signaling
pathway. The expression of Parkin promotes the recruitment of transforming growth
factor beta (TGF-beta)-activated kinase 1 (TAK1), nuclear factor-kappaB (NF
kappaB) essential molecule (NEMO), Sharpin and A20 in complex I associated with
TNFR1 upon TNFalpha stimulation. Ubiquitination of RIPK1 by Parkin increases the
activation of NF-kappaB and mitogen-activated protein kinases (MAPKs) by
promoting the phosphorylation of inhibitor of kappa B kinase (IKK)alpha/beta and
IkappaBalpha and nuclear translocation of p65. Thus, we conclude that Parkin
modulates the K63 ubiquitination status of RIPK1 to promote the activation of NF
kappaB and MAPKs.
PMID- 29955051
TI - An all-dielectric metasurface as a broadband optical frequency mixer.
AB - A frequency mixer is a nonlinear device that combines electromagnetic waves to
create waves at new frequencies. Mixers are ubiquitous components in modern radio
frequency technology and microwave signal processing. The development of
versatile frequency mixers for optical frequencies remains challenging: such
devices generally rely on weak nonlinear optical processes and, thus, must
satisfy phase-matching conditions. Here we utilize a GaAs-based dielectric
metasurface to demonstrate an optical frequency mixer that concurrently generates
eleven new frequencies spanning the ultraviolet to near-infrared. The even and
odd order nonlinearities of GaAs enable our observation of second-harmonic, third
harmonic, and fourth-harmonic generation, sum-frequency generation, two-photon
absorption-induced photoluminescence, four-wave mixing and six-wave mixing. The
simultaneous occurrence of these seven nonlinear processes is assisted by the
combined effects of strong intrinsic material nonlinearities, enhanced
electromagnetic fields, and relaxed phase-matching requirements. Such
ultracompact optical mixers may enable a plethora of applications in biology,
chemistry, sensing, communications, and quantum optics.
PMID- 29955052
TI - FRET-enhanced photostability allows improved single-molecule tracking of proteins
and protein complexes in live mammalian cells.
AB - A major challenge in single-molecule imaging is tracking the dynamics of proteins
or complexes for long periods of time in the dense environments found in living
cells. Here, we introduce the concept of using FRET to enhance the photophysical
properties of photo-modulatable (PM) fluorophores commonly used in such studies.
By developing novel single-molecule FRET pairs, consisting of a PM donor
fluorophore (either mEos3.2 or PA-JF549) next to a photostable acceptor dye
JF646, we demonstrate that FRET competes with normal photobleaching kinetic
pathways to increase the photostability of both donor fluorophores. This effect
was further enhanced using a triplet-state quencher. Our approach allows us to
significantly improve single-molecule tracking of chromatin-binding proteins in
live mammalian cells. In addition, it provides a novel way to track the
localization and dynamics of protein complexes by labeling one protein with the
PM donor and its interaction partner with the acceptor dye.
PMID- 29955053
TI - Layered liquid crystal elastomer actuators.
AB - Liquid crystalline elastomers (LCEs) are soft, anisotropic materials that exhibit
large shape transformations when subjected to various stimuli. Here we
demonstrate a facile approach to enhance the out-of-plane work capacity of these
materials by an order of magnitude, to nearly 20 J/kg. The enhancement in force
output is enabled by the development of a room temperature polymerizable
composition used both to prepare individual films, organized via directed self
assembly to retain arrays of topological defect profiles, as well as act as an
adhesive to combine the LCE layers. The material actuator is shown to displace a
load >2500* heavier than its own weight nearly 0.5 mm.
PMID- 29955054
TI - The origin and remolding of genomic islands of differentiation in the European
sea bass.
AB - Speciation is a complex process that leads to the progressive establishment of
reproductive isolation barriers between diverging populations. Genome-wide
comparisons between closely related species have revealed the existence of
heterogeneous divergence patterns, dominated by genomic islands of increased
divergence supposed to contain reproductive isolation loci. However, this
divergence landscape only provides a static picture of the dynamic process of
speciation, during which confounding mechanisms unrelated to speciation can
interfere. Here we use haplotype-resolved whole-genome sequences to identify the
mechanisms responsible for the formation of genomic islands between Atlantic and
Mediterranean sea bass lineages. Local ancestry patterns show that genomic
islands first emerged in allopatry through linked selection acting on a
heterogeneous recombination landscape. Then, upon secondary contact, preexisting
islands were strongly remolded by differential introgression, revealing variable
fitness effects among regions involved in reproductive isolation. Interestingly,
we find that divergent regions containing ancient polymorphisms conferred the
strongest resistance to introgression.
PMID- 29955055
TI - Possible nitrogen fertilization of the early Earth Ocean by microbial continental
ecosystems.
AB - While significant efforts have been invested in reconstructing the early
evolution of the Earth's atmosphere-ocean-biosphere biogeochemical nitrogen
cycle, the potential role of an early continental contribution by a terrestrial,
microbial phototrophic biosphere has been largely overlooked. By transposing to
the Archean nitrogen fluxes of modern topsoil communities known as biological
soil crusts (terrestrial analogs of microbial mats), whose ancestors might have
existed as far back as 3.2 Ga ago, we show that they could have impacted the
evolution of the nitrogen cycle early on. We calculate that the net output of
inorganic nitrogen reaching the Precambrian hydrogeological system could have
been of the same order of magnitude as that of modern continents for a range of
inhabited area as small as a few percent of that of present day continents. This
contradicts the assumption that before the Great Oxidation Event, marine and
continental biogeochemical nitrogen cycles were disconnected.
PMID- 29955056
TI - Long-haul optical transmission link using low-noise phase-sensitive amplifiers.
AB - The capacity and reach of long-haul fiber optical communication systems is
limited by in-line amplifier noise and fiber nonlinearities. Phase-sensitive
amplifiers add 6 dB less noise than conventional phase-insensitive amplifiers,
such as erbium-doped fiber amplifiers, and they can provide nonlinearity
mitigation after each span. Realizing a long-haul transmission link with in-line
phase-sensitive amplifiers providing simultaneous low-noise amplification and
nonlinearity mitigation is challenging and to date no such transmission link has
been demonstrated. Here, we demonstrate a multi-channel-compatible and modulation
format-independent long-haul transmission link with in-line phase-sensitive
amplifiers. Compared to a link amplified by conventional erbium-doped fiber
amplifiers, we demonstrate a reach improvement of 5.6 times at optimal launch
powers with the phase-sensitively amplified link operating at a total accumulated
nonlinear phase shift of 6.2 rad. The phase-sensitively amplified link transmits
two data-carrying waves, thus occupying twice the bandwidth and propagating twice
the total power compared to the phase-insensitively amplified link.
PMID- 29955057
TI - Neuromorphic computing with multi-memristive synapses.
AB - Neuromorphic computing has emerged as a promising avenue towards building the
next generation of intelligent computing systems. It has been proposed that
memristive devices, which exhibit history-dependent conductivity modulation,
could efficiently represent the synaptic weights in artificial neural networks.
However, precise modulation of the device conductance over a wide dynamic range,
necessary to maintain high network accuracy, is proving to be challenging. To
address this, we present a multi-memristive synaptic architecture with an
efficient global counter-based arbitration scheme. We focus on phase change
memory devices, develop a comprehensive model and demonstrate via simulations the
effectiveness of the concept for both spiking and non-spiking neural networks.
Moreover, we present experimental results involving over a million phase change
memory devices for unsupervised learning of temporal correlations using a spiking
neural network. The work presents a significant step towards the realization of
large-scale and energy-efficient neuromorphic computing systems.
PMID- 29955058
TI - Inhibition of excessive autophagy and mitophagy mediates neuroprotective effects
of URB597 against chronic cerebral hypoperfusion.
AB - URB597 (URB) has therapeutic potential for treating chronic cerebral
hypoperfusion (CCH)-induced neuronal death. The present study investigated the
protective effects of URB on autopahgy and mitophagy in a CCH model as well as
the underlying mechanisms. The ultrastructural changes were examined by electron
microscopy. The mitochondrial membrane potential was assessed by
immunofluorescence. The expressions of autophagy-related proteins (beclin-1, p62,
and LC3), lysosome-related proteins (CTSD and LAMP1), and mitophagy-related
proteins (BNIP3, cyt C and parkin) were evaluated by western blotting, and the
interaction of beclin-1 and Bcl-2 were determined by immunoprecipitation. CCH
significantly decreased the protein expression of p62, CTSD, and LAMP1 and
increased the protein expression of beclin-1, parkin, and BNIP3, the LC3-II to
LC3-I ratio, and the release of cyt C from mitochondria to cytoplasm.
Furthermore, CCH induced the accumulation of ubiquitinated proteins in PSDs.
However, URB significantly reversed these results. Besides, URB significantly
inhibited the beclin-1 from beclin-1/Bcl-2 complex to whole-cell lysates. The
above results indicate that URB could inhibit impaired autophagy degradation and
the disruption of beclin-1/Bcl-2 complex and subsequently cut off BNIP3-cyt C-
and parkin-required mitophagy, finally preventing the abnormal excessive
autophagy and mitophagy. These findings provide new insights that URB is a
promising agent for therapeutic management of CCH.
PMID- 29955059
TI - Author Correction: TRPV1 SUMOylation regulates nociceptive signaling in models of
inflammatory pain.
AB - In the originally published version of this Article, the affiliation details for
Yan Wang, Yingwei Gao, Qi Deng, Yangbo Wang, Tian Zhou, Yingping Wang, Huiqing
Liu, Ruining Ma, Jinke Cheng and Yong Li incorrectly omitted 'Shanghai Jiao Tong
University'. This has now been corrected in both the PDF and HTML versions of the
Article.' Furthermore, the Supplementary Information file originally associated
with this Article inadvertently omitted Supplementary Figure 9. The error has now
been fixed and the corrected version Supplementary Information PDF is available
to download from the HTML version of the Article.
PMID- 29955060
TI - Influenza.
PMID- 29955061
TI - Glutamic acid-valine-citrulline linkers ensure stability and efficacy of antibody
drug conjugates in mice.
AB - Valine-citrulline linkers are commonly used as enzymatically cleavable linkers
for antibody-drug conjugates. While stable in human plasma, these linkers are
unstable in mouse plasma due to susceptibility to an extracellular
carboxylesterase. This instability often triggers premature release of drugs in
mouse circulation, presenting a molecular design challenge. Here, we report that
an antibody-drug conjugate with glutamic acid-valine-citrulline linkers is
responsive to enzymatic drug release but undergoes almost no premature cleavage
in mice. We demonstrate that this construct exhibits greater treatment efficacy
in mouse tumor models than does a valine-citrulline-based variant. Notably, our
antibody-drug conjugate contains long spacers facilitating the protease access to
the linker moiety, indicating that our linker assures high in vivo stability
despite a high degree of exposure. This technology could add flexibility to
antibody-drug conjugate design and help minimize failure rates in pre-clinical
studies caused by linker instability.
PMID- 29955062
TI - Molecular basis of Tousled-Like Kinase 2 activation.
AB - Tousled-like kinases (TLKs) are required for genome stability and normal
development in numerous organisms and have been implicated in breast cancer and
intellectual disability. In humans, the similar TLK1 and TLK2 interact with each
other and TLK activity enhances ASF1 histone binding and is inhibited by the DNA
damage response, although the molecular mechanisms of TLK regulation remain
unclear. Here we describe the crystal structure of the TLK2 kinase domain. We
show that the coiled-coil domains mediate dimerization and are essential for
activation through ordered autophosphorylation that promotes higher order
oligomers that locally increase TLK2 activity. We show that TLK2 mutations
involved in intellectual disability impair kinase activity, and the docking of
several small-molecule inhibitors of TLK activity suggest that the crystal
structure will be useful for guiding the rationale design of new inhibition
strategies. Together our results provide insights into the structure and
molecular regulation of the TLKs.
PMID- 29955063
TI - Natural selection of a GSK3 determines rice mesocotyl domestication by
coordinating strigolactone and brassinosteroid signaling.
AB - Mesocotyl is the crucial organ for pushing buds out of deep water or soil after
germination in monocots. Deep direct seeding or mechanized dry seeding
cultivation practice requires rice cultivars having long mesocotyl. However, the
mechanisms of mesocotyl elongation and domestication remain unknown. Here, our
genome-wide association study (GWAS) reveals that natural variations of OsGSK2, a
conserved GSK3-like kinase involved in brassinosteroid signaling, determine rice
mesocotyl length variation. Variations in the coding region of OsGSK2 alter its
kinase activity. It is selected for mesocotyl length variation during
domestication. Molecular analyses show that brassinosteroid-promoted mesocotyl
elongation functions by suppressing the phosphorylation of an U-type cyclin, CYC
U2, by OsGSK2. Importantly, the F-box protein D3, a major positive component in
strigolactone signaling, can degrade the OsGSK2-phosphorylated CYC U2 to inhibit
mesocotyl elongation. Together, these results suggest that OsGSK2 is selected to
regulate mesocotyl length by coordinating strigolactone and brassinosteroid
signaling during domestication.
PMID- 29955064
TI - Zero-static power radio-frequency switches based on MoS2 atomristors.
AB - Recently, non-volatile resistance switching or memristor (equivalently,
atomristor in atomic layers) effect was discovered in transitional metal
dichalcogenides (TMD) vertical devices. Owing to the monolayer-thin transport and
high crystalline quality, ON-state resistances below 10 Omega are achievable,
making MoS2 atomristors suitable as energy-efficient radio-frequency (RF)
switches. MoS2 RF switches afford zero-hold voltage, hence, zero-static power
dissipation, overcoming the limitation of transistor and mechanical switches.
Furthermore, MoS2 switches are fully electronic and can be integrated on
arbitrary substrates unlike phase-change RF switches. High-frequency results
reveal that a key figure of merit, the cutoff frequency (fc), is about 10 THz for
sub-MUm2 switches with favorable scaling that can afford fc above 100 THz for
nanoscale devices, exceeding the performance of contemporary switches that suffer
from an area-invariant scaling. These results indicate a new electronic
application of TMDs as non-volatile switches for communication platforms,
including mobile systems, low-power internet-of-things, and THz beam steering.
PMID- 29955065
TI - Designing a magnesium alloy with high strength and high formability.
AB - Although magnesium alloys, as the lightest structural alloys, offer significant
potential for automotive applications, their applications remain limited due to
their poor formability at room temperature. Since the strategies used for
improving formability usually result in a degradation of strength, there are no
high strength magnesium alloys showing good formability. Here we report an alloy
design concept that can simultaneously provide high strength and good
formability. Such designed alloy when subjected to an appropriate processing
technique shows a combination of strength and formability that surpasses those of
the existing magnesium alloys reported so far. The alloy design concept used in
the present study is based on the utilization of alloying elements that can
induce precipitation, as well as maximize the segregation of other texture
controlling alloying elements. Such developed alloy is expected to broaden the
application of Mg alloy sheets, which are now starting to gain acceptance by
automotive industries.
PMID- 29955066
TI - Very large tunneling magnetoresistance in layered magnetic semiconductor CrI3.
AB - Magnetic layered van der Waals crystals are an emerging class of materials giving
access to new physical phenomena, as illustrated by the recent observation of 2D
ferromagnetism in Cr2Ge2Te6 and CrI3. Of particular interest in semiconductors is
the interplay between magnetism and transport, which has remained unexplored.
Here we report magneto-transport measurements on exfoliated CrI3 crystals. We
find that tunneling conduction in the direction perpendicular to the crystalline
planes exhibits a magnetoresistance as large as 10,000%. The evolution of the
magnetoresistance with magnetic field and temperature reveals that the phenomenon
originates from multiple transitions to different magnetic states, whose possible
microscopic nature is discussed on the basis of all existing experimental
observations. This observed dependence of the conductance of a tunnel barrier on
its magnetic state is a phenomenon that demonstrates the presence of a strong
coupling between transport and magnetism in magnetic van der Waals
semiconductors.
PMID- 29955067
TI - Doping-induced structural phase transition in cobalt diselenide enables enhanced
hydrogen evolution catalysis.
AB - Transition metal dichalcogenide materials have been explored extensively as
catalysts to negotiate the hydrogen evolution reaction, but they often run at a
large excess thermodynamic cost. Although activating strategies, such as defects
and composition engineering, have led to remarkable activity gains, there remains
the requirement for better performance that aims for real device applications. We
report here a phosphorus-doping-induced phase transition from cubic to
orthorhombic phases in CoSe2. It has been found that the achieved orthorhombic
CoSe2 with appropriate phosphorus dopant (8 wt%) needs the lowest overpotential
of 104 mV at 10 mA cm-2 in 1 M KOH, with onset potential as small as -31 mV. This
catalyst demonstrates negligible activity decay after 20 h of operation. The
striking catalysis performance can be attributed to the favorable electronic
structure and local coordination environment created by this doping-induced
structural phase transition strategy.
PMID- 29955068
TI - Influenza.
PMID- 29955069
TI - Motion cues tune social influence in shoaling fish.
AB - Social interactions have important consequences for individual fitness.
Collective actions, however, are notoriously context-dependent and identifying
how animals rapidly weigh the actions of others despite environmental uncertainty
remains a fundamental challenge in biology. By exposing zebrafish (Danio rerio)
to virtual fish silhouettes in a maze we isolated how the relative strength of a
visual feature guides individual directional decisions and, subsequently, tunes
social influence. We varied the relative speed and coherency with which a portion
of silhouettes adopted a direction (leader/distractor ratio) and established that
solitary zebrafish display a robust optomotor response to follow leader
silhouettes that moved much faster than their distractors, regardless of stimulus
coherency. Although recruitment time decreased as a power law of zebrafish group
size, individual decision times retained a speed-accuracy trade-off, suggesting a
benefit to smaller group sizes in collective decision-making. Directional
accuracy improved regardless of group size in the presence of the faster moving
leader silhouettes, but without these stimuli zebrafish directional decisions
followed a democratic majority rule. Our results show that a large difference in
movement speeds can guide directional decisions within groups, thereby providing
individuals with a rapid and adaptive means of evaluating social information in
the face of uncertainty.
PMID- 29955071
TI - Evaluating the Contribution of North American Zoos and Aquariums to Endangered
Species Recovery.
AB - The challenge of recovering threatened species necessitates collaboration among
diverse conservation partners. Zoos and aquariums have long partnered with other
conservation organizations and government agencies to help recover species
through a range of in situ and ex situ conservation projects. These efforts tend
to be conducted by individual facilities and for individual species, and thus the
scope and magnitude of these actions at the national level are not well
understood. Here we evaluate the means and extent to which North American zoos
and aquariums contribute to the recovery of species listed under the U.S.
Endangered Species Act (ESA), by synthesizing data from federal recovery plans
for listed species and from annual surveys conducted by the Association of Zoos
and Aquariums. We found that in addition to managing ex situ assurance
populations, zoos frequently conduct conservation research and field-based
population monitoring and assessments. Cooperatively managed populations in zoos
tend to focus on species that are not listed on the ESA or on foreign listings,
and thus it may be beneficial for zoos to manage more native threatened species.
Our results highlight the existing contributions, but also identify additional
opportunities for the zoo community to help recover threatened species.
PMID- 29955070
TI - Excited-state vibrational dynamics toward the polaron in methylammonium lead
iodide perovskite.
AB - Hybrid organic-inorganic perovskites have attractive optoelectronic properties
including exceptional solar cell performance. The improved properties of
perovskites have been attributed to polaronic effects involving stabilization of
localized charge character by structural deformations and polarizations. Here we
examine the Pb-I structural dynamics leading to polaron formation in
methylammonium lead iodide perovskite by transient absorption, time-domain Raman
spectroscopy, and density functional theory. Methylammonium lead iodide
perovskite exhibits excited-state coherent nuclear wave packets oscillating at
~20, ~43, and ~75 cm-1 which involve skeletal bending, in-plane bending, and c
axis stretching of the I-Pb-I bonds, respectively. The amplitudes of these wave
packet motions report on the magnitude of the excited-state structural changes,
in particular, the formation of a bent and elongated octahedral PbI64- geometry.
We have predicted the excited-state geometry and structural changes between the
neutral and polaron states using a normal-mode projection method, which supports
and rationalizes the experimental results. This study reveals the polaron
formation via nuclear dynamics that may be important for efficient charge
separation.
PMID- 29955072
TI - Nanostructure, structural stability, and diffusion characteristics of layered
coatings for heat-assisted magnetic recording head media.
AB - The intense laser heating in heat-assisted magnetic recording (HAMR) has been a
major hindrance to HAMR technology from becoming commercially viable. Thermal
damage of the near-field transducer (NFT) and write pole (WP) embedded in the
trailing edge of the magnetic head due to failure of the protective carbon
overcoat after prolonged heating at an elevated temperature are major obstacles.
Therefore, the main objective of this study was to develop an effective coating
method for HAMR heads. This was accomplished by introducing a new class of
layered coatings consisting of ultrathin amorphous carbon (a-C) overcoat,
adhesion (SiN) layer, and buffer (NiCr or TaOx) layer sequentially deposited onto
Au and FeCo base layers to mimic the layer stacking of NFT and WP elements,
respectively. The structural stability of the a-C overcoats and diffusion
characteristics of each comprising layer under conditions of heating at 350
degrees C for 30 min in an Ar atmosphere were investigated by high-resolution
transmission electron microscopy (HRTEM), scanning transmission electron
microscopy (STEM), and electron energy loss spectroscopy (EELS). For most
stacking configurations the HRTEM/STEM and EELS results generally revealed some
layer intermixing and minute carbon atom rehybridization in the heated a-C
overcoats. The findings of this investigation suggest that further optimization
of the developed layered coatings can provide a viable solution to thermal damage
of HAMR heads.
PMID- 29955073
TI - Prolonged abstinence from cocaine or morphine disrupts separable valuations
during decision conflict.
AB - Neuroeconomic theories propose changes in decision making drive relapse in
recovering drug addicts, resulting in continued drug use despite stated wishes
not to. Such conflict is thought to arise from multiple valuation systems
dependent on separable neural components, yet many neurobiology of addiction
studies employ only simple tests of value. Here, we tested in mice how prolonged
abstinence from different drugs affects behavior in a neuroeconomic foraging task
that reveals multiple tests of value. Abstinence from repeated cocaine and
morphine disrupts separable decision-making processes. Cocaine alters
deliberation-like behavior prior to choosing a preferred though economically
unfavorable offer, while morphine disrupts re-evaluations after rapid initial
decisions. These findings suggest that different drugs have long-lasting effects
precipitating distinct decision-making vulnerabilities. Our approach can guide
future refinement of decision-making behavioral paradigms and highlights how
grossly similar behavioral maladaptations may mask multiple underlying, parallel,
and dissociable processes that treatments for addiction could potentially target.
PMID- 29955074
TI - Lacrimal Canaliculus Imaging Using Optical Coherence Tomography Dacryography.
AB - Lacrimal canaliculus (LC) has a key role in tear drainage, but it is difficult to
evaluate the LC in detail, using the existing examinations. In this study, our
novel LC imaging technique provided the high-resolution images of LC in a non
invasive manner. Three-dimensional images of LC were acquired via the palpebral
conjunctiva from 20 healthy volunteers (20 eyes) and 10 patients with various
lacrimal disorders (10 eyes), using optical coherence tomography (OCT)
dacryography (OCTD). The LC images showed morphological differences between the
vertical and horizontal segments. The function of LC could be evaluated by
measuring the intralumen signal intensity over time after instillation of a
contrast agent (2% rebamipide ophthalmic suspension). OCTD clearly visualised the
blind extremity of the LC in four patients with punctal obstruction, which was
useful for deciding the punctal incision location. In one patient with
canalicular obstruction, contrast agent successfully highlighted the LC that had
become narrow toward the site of obstruction. Significant differences were not
found in the function and morphology of LC between the patients with NLDO and the
healthy subjects. OCTD may be a useful tool for LC imaging, because it
facilitates quantitative and simultaneous evaluation of LC morphology and
function.
PMID- 29955075
TI - HPV infection and bacterial microbiota in the placenta, uterine cervix and oral
mucosa.
AB - We investigated the association between HPV infection and bacterial microbiota
composition in the placenta, uterine cervix and mouth in thirty-nine women. HPV
DNA genotyping of 24 types was conducted using Multimetrix(r). Microbiota
composition was characterized by 16S rRNA gene sequencing. HPV DNA was detected
in 33% of placenta, 23% cervical and 33% oral samples. HPV16 was the most
frequent type in all regions. HPV infection was associated with higher microbiota
richness (p = 0.032) in the mouth but did not influence microbial diversity or
richness in other samples. HPV infection was associated with higher abundance of
Lactobacillaceae (p = 0.0036) and Ureaplasma (LDA score > 4.0, p < 0.05) in the
placenta, Haemophilus (p = 0.00058) and Peptostreptococcus (p = 0.0069) genus in
the cervix and Selenomonas spp. (p = 0.0032) in the mouth compared to HPV
negative samples. These data suggest altered bacterial microbiota composition in
HPV positive placenta, cervix and mouth. Whether the changes in bacterial
microbiota predispose or result from HPV remains to be determined in future
studies.
PMID- 29955076
TI - Non-Linear Self-Heating in Organic Transistors Reaching High Power Densities.
AB - The improvement of the performance of organic thin-film transistors is driven by
novel materials and improved device engineering. Key developments are a
continuous increase of the charge carrier mobility, a scale-down of transistor
dimensions, and the reduction of contact resistance. Furthermore, new transistor
designs such as vertical devices are introduced to benefit from drastically
reduced channel length while keeping the effort for structuring moderate. Here,
we show that a strong electrothermal feedback occurs in organic transistors,
ultimately leading to output characteristics with regions of S-shaped negative
differential resistance. For that purpose, we use an organic permeable-base
transistor (OPBT) with outstanding current densities, where a strong and
reproducible, non-linear electrothermal feedback is revealed. We derive an
analytical description of the temperature dependent current-voltage behavior and
offer a rapid investigation method for material systems, where a temperature
activated conductivity can be observed.
PMID- 29955079
TI - Geodetic evidence for interconnectivity between Aira and Kirishima magmatic
systems, Japan.
AB - It is not known whether clustered or aligned volcanic edifices at the Earth
surface have connected magmatic systems at depth. Previously suggested by
geological records of paired eruptions, volcano interconnectivity still lacks
proper geodetic evidence. Here we use GPS time-series and deformation modeling to
show how Aira caldera and Kirishima, two adjacent volcanic centers in Kagoshima
graben (southern Japan), interacted during Kirishima unrest in 2011. Whereas Aira
caldera had been inflating steadily for two decades, it deflated during the
eruption of Kirishima which started with a large-volume lava extrusion. This
deflation, which cannot be explained by stress changes, is interpreted as the
result of magma withdrawal from the Aira system during the Kirishima
replenishment phase. This study highlights the behavior of connected neighboring
volcanic systems before and after a large eruption, and the importance of taking
into account volcano interactions in eruption probability models.
PMID- 29955078
TI - 7B2 chaperone knockout in APP model mice results in reduced plaque burden.
AB - Impairment of neuronal proteostasis is a hallmark of Alzheimer's and other
neurodegenerative diseases. However, the underlying molecular mechanisms leading
to pathogenic protein aggregation, and the role of secretory chaperone proteins
in this process, are poorly understood. We have previously shown that the neural
and endocrine-specific secretory chaperone 7B2 potently blocks in vitro
fibrillation of Abeta42. To determine whether 7B2 can function as a chaperone in
vivo, we measured plaque formation and performed behavioral assays in 7B2
deficient mice in an hAPPswe/PS1dE9 Alzheimer's model mouse background.
Surprisingly, immunocytochemical analysis of cortical levels of thioflavin S- and
Abeta-reactive plaques showed that APP mice with a partial or complete lack of
7B2 expression exhibited a significantly lower number and burden of thioflavin S
reactive, as well as Abeta-immunoreactive, plaques. However, 7B2 knockout did not
affect total brain levels of either soluble or insoluble Abeta. While hAPP model
mice performed poorly in the Morris water maze, their brain 7B2 levels did not
impact performance. Since 7B2 loss reduced amyloid plaque burden, we conclude
that brain 7B2 can impact Abeta disposition in a manner that facilitates plaque
formation. These results are reminiscent of prior findings in hAPP model mice
lacking the ubiquitous secretory chaperone clusterin.
PMID- 29955077
TI - Inflammatory cytokines and biofilm production sustain Staphylococcus aureus
outgrowth and persistence: a pivotal interplay in the pathogenesis of Atopic
Dermatitis.
AB - Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus
aureus colonization. However, the mechanisms driving this process as well as the
impact of S. aureus in AD pathogenesis are still incompletely understood. In this
study, we analysed the role of biofilm in sustaining S. aureus chronic
persistence and its impact on AD severity. Further we explored whether key
inflammatory cytokines overexpressed in AD might provide a selective advantage to
S. aureus. Results show that the strength of biofilm production by S. aureus
correlated with the severity of the skin lesion, being significantly higher (P <
0.01) in patients with a more severe form of the disease as compared to those
individuals with mild AD. Additionally, interleukin (IL)-beta and interferon
gamma (IFN-gamma), but not interleukin (IL)-6, induced a concentration-dependent
increase of S. aureus growth. This effect was not observed with coagulase
negative staphylococci isolated from the skin of AD patients. These findings
indicate that inflammatory cytokines such as IL1-beta and IFN-gamma, can
selectively promote S. aureus outgrowth, thus subverting the composition of the
healthy skin microbiome. Moreover, biofilm production by S. aureus plays a
relevant role in further supporting chronic colonization and disease severity,
while providing an increased tolerance to antimicrobials.
PMID- 29955080
TI - Reply to 'Increased food supply mitigates ocean acidification effects on
calcification but exacerbates effects on growth'.
AB - In the Brown et al. study 'Increased food supply mitigates ocean acidification
effects on calcification but exacerbates effects on growth' they show
disagreement with the tested hypothesis and data analysis methodology used in our
2016 study. We acknowledge careful criticism and a constructive dialogue are
necessary to progress science and address these issues in this reply.Replying to:
Brown et al. Sci. Rep. 8 (2018); https://doi.org/10.1038/s41598-018-28012-w .
PMID- 29955081
TI - Processing Homophones Interactively: Evidence from eye-movement data.
AB - The question of how to process an ambiguous word in context has been long-studied
in psycholinguistics and the present study examined this question further by
investigating the spoken word recognition processes of Cantonese homophones (a
common type of ambiguous word) in context. Sixty native Cantonese listeners were
recruited to participate in an eye-tracking experiment. Listeners were instructed
to listen carefully to a sentence ending with a Cantonese homophone and then look
at different visual probes (either Chinese characters or line-drawing pictures)
presented on the computer screen simultaneously. Two findings were observed.
First, the results revealed that sentence context exerted an early effect on
homophone processes. Second, visual probes that serve as phonological competitors
only had a weak effect on the spoken word recognition processes. Consistent with
previous studies, the patterns of eye-movement results appeared to support an
interactive processing approach in homophone recognition.
PMID- 29955082
TI - Co-protoporphyrin IX and Sn-protoporphyrin IX inactivate Zika, Chikungunya and
other arboviruses by targeting the viral envelope.
AB - The global situation of diseases transmitted by arthropod-borne viruses such as
Dengue (DENV), Yellow Fever (YFV), Chikungunya (CHIKV) and Zika (ZIKV) viruses is
alarming and treatment of human infection by these arboviruses faces several
challenges. The discovery of broad-spectrum antiviral molecules, able to
inactivate different groups of viruses, is an interesting approach. The viral
envelope is a common structure among arboviruses, being a potential target for
antivirals. Porphyrins are amphipathic molecules able to interact with membranes
and absorb light, being widely used in photodynamic therapy. Previously, we
showed that heme, Co-protoporphyrin IX (CoPPIX) and Sn-protoporphyrin IX (SnPPIX)
directly inactivate DENV and YFV infectious particles. Here we demonstrate that
the antiviral activity of these porphyrins can be broadened to CHIKV, ZIKV,
Mayaro virus, Sindbis virus and Vesicular Stomatitis virus. Porphyrin treatment
causes viral envelope protein loss, affecting viral morphology, adsorption and
entry into target cells. Also, light-stimulation enhanced the SnPPIX activity
against all tested arboviruses. In summary, CoPPIX and SnPPIX were shown to be
efficient broad-spectrum compounds to inactivate medically and veterinary
important viruses.
PMID- 29955083
TI - Evaluation of Performance Parameters of the Disposable Flexible Ureterorenoscope
(LITHOVUE) in Patients with Renal Stones: A Prospective, Observational, Single
arm, Multicenter Study.
AB - We investigated performance parameters of disposable flexible ureterorenoscopy
(LITHOVUE) in patients with renal stones in a prospective, multicenter,
observational study. Sixty two patients who underwent ureterorenoscopic surgery
by LITHOVUE were included. Surgeons using a numerical scale, evaluated the
maneuverability of the scopes and general perceptions of visibility related to
the monitor and irrigation systems. General pain and fatigue scores were
evaluated and compared to existing scopes. Mean patient age was 57.3 years and
stone size was 15.4 mm. Clinical success of overall stone removal was 82.3%.
Complications occurred in 4 cases of the Clavien classification grade I in a
single case and II in 3 cases. Comparative parameters of maneuverability,
perception of the monitor system and perception of the irrigation channel were
2.5, 2.5, and 3.0, respectively. The most favorable evaluation of physical strain
was about 'shoulder fatigue' and 'hand fatigue'. Unfavorable evaluations were
recorded for 'wrist stiffness' and 'thumb fatigue'. Maximal deflection angles of
270 degrees were preserved in 53 cases (85.5%). No pre-stenting procedure and
the longer operative time were significant predictors of poorly-preserved
deflection angles <270 degrees . LITHOVUE showed good maneuverability and
perception scores for the monitor and irrigation systems. LITHOVUE received
favorable evaluations on pain and fatigue scores.
PMID- 29955084
TI - Instability of personal human metabotype is linked to all-cause mortality.
AB - Disruption of metabolic homeostasis is an important factor in many diseases.
Various metabolites have been linked to higher risk of morbidity and all-cause
mortality using metabolomics in large population-based cohorts. In these studies,
baseline metabolite levels were compared across subjects to identify associations
with health outcomes, implying the existence of 'healthy' concentration ranges
that are equally applicable to all individuals. Here, we focused on intra
individual changes in metabolite levels over time and their link to mortality,
potentially allowing more personalized risk assessment. We analysed targeted
metabolomics data for 134 blood metabolites from 1409 participants in the
population-based CARLA cohort at baseline and after four years. Metabotypes of
the majority of participants (59%) were extremely stable over time indicated by
high correlation between the subjects' metabolite profiles at the two time
points. Metabotype instability and, in particular, decrease of valine were
associated with higher risk of all-cause mortality in 7.9 years of follow-up
(hazard ratio (HR) = 1.5(95%CI = 1.0-2.3) and 0.2(95%CI = 0.1-0.3)) after
multifactorial adjustment. Excluding deaths that occurred in the first year after
metabolite profiling showed similar results (HR = 1.8(95%CI = 1.1-2.8)). Lower
metabotype stability was also associated with incident cardiovascular disease (OR
= 1.2(95%CI = 1.0-1.3)). Therefore, changes in the personal metabotype might be a
valuable indicator of pre-clinical disease.
PMID- 29955086
TI - Interleukin-6 determines protein stabilization of DNA methyltransferases and
alters DNA promoter methylation of genes associated with insulin signaling and
angiogenesis.
AB - Individuals with type 2 diabetes (T2D) display vascular insulin resistance and
decreased nitric oxide production leading to vasoconstriction and
atherosclerosis. Soluble factors such as pro-inflammatory molecules, and various
genetic and epigenetic mechanisms have been implicated to induce insulin
resistance in vascular endothelial cells. Epigenetic mechanisms such as altered
promoter DNA methylation have been demonstrated in development and progression of
metabolic disorders and atherosclerosis. However, underlying precise epigenetic
mechanisms regulating cross talk between insulin signaling genes and inflammation
in vascular cells remains to be fully understood. Human endothelial cells when
(a) treated with interleukin-6 (IL-6) and insulin together, (b) pretreated with
IL-6, and (c) under hyperinsulinemic conditions led to a state of vascular
insulin resistance resulting in decreased Akt/eNOS activation and subsequent
stabilization of STAT3 phosphorylation. IL-6 abrogated insulin effects on
angiogenesis in 3D spheroid and matrigel assays. IL-6-induced insulin resistance
was associated with decreased activity of DNA methyltransferase isoforms and
global DNA hypomethylation, which inversely correlated with S-phase of cell
cycle. CpG microarray analysis in IL-6 treated endothelial cells revealed
promoters associated hypo- and hypermethylation of 199 and 98 genes respectively.
Promoter DNA methylation status of genes associated with insulin signaling and
angiogenesis such as RPS6KA2, PIK3R2, FOXD3, EXOC7, MAP3K8, ITPKB, EPHA6, IGF1R,
and FOXC2 were validated by bisulfite DNA sequencing. Concentration and time
dependent analysis revealed that IL-6 reduced DNMT1 and DNMT3B but not DNMT3A
protein levels. Our data indicate a causal link between IL-6-induced changes in
global and promoter-specific DNA methylation, due to reduced DNMT1 and DNMT3B
protein levels leading to altered expression of critical genes involved in
insulin signaling and angiogenesis.
PMID- 29955085
TI - The impact of obesity in cognitive and memory dysfunction in obstructive sleep
apnea syndrome.
AB - OBJECTIVE: Obstructive sleep apnea (OSA), a sleep disorder, results in decreased
daytime alertness and neurocognitive dysfunction. Obesity is considered a major
risk factor for the development and progression of OSA and the resulting
cognitive dysfunction. However, the effect of obesity on neurocognitive
dysfunction in OSA has been rarely investigated. METHODS: Eighty-three patients
with moderate to severe OSA syndrome were recruited in our study. After matching
for education, age, and body mass index (BMI), 40 patients were enrolled into our
study with matched obese (BMI ? 30) and non-obese (BMI < 30) groups. All enrolled
patients completed a polysomnographic study, sleepiness questionnaires, and
attention, cognitive, and memory function tests. RESULTS: Compared to obese OSA
patients, non-obese OSA patients had shorter reaction times in the psychomotor
vigilance task but not the Flanker or Stroop cognitive tasks. Additionally, obese
OSA patients had a reduced capacity for working memory relative to non-obese OSA
patients. CONCLUSIONS: Obesity had a significant effect on OSA patients in our
study, including delayed reaction times in the psychomotor vigilance task and a
decrease in working memory.
PMID- 29955087
TI - miR-137 is a tumor suppressor in endometrial cancer and is repressed by DNA
hypermethylation.
AB - Endometrial cancer is the most common gynecological cancer in the United States.
We wanted to identify epigenetic aberrations involving microRNAs (miRNAs), whose
genes become hypermethylated in endometrial primary tumors. By integrating known
miRNA sequences from the miRNA database (miRBase) with DNA methylation data from
methyl-CpG-capture sequencing, we identified 111 differentially methylated
regions (DMRs) associated with CpG islands (CGIs) and miRNAs. Among them, 22 DMRs
related to 29 miRNAs and within 8 kb of CGIs were hypermethylated in endometrial
tumors but not in normal endometrium. miR-137 was further validated in additional
endometrial primary tumors. Hypermethylation of miR-137 was found in both
endometrioid and serous endometrial cancer (P < 0.01), and it led to the loss of
miR-137 expression. Treating hypermethylated endometrial cancer cells with
epigenetic inhibitors reactivated miR-137. Moreover, genetic overexpression of
miR-137 suppressed cancer cell proliferation and colony formation in vitro. When
transfected cancer cells were implanted into nude mice, the cells that
overexpressed miR-137 grew more slowly and formed smaller tumors (P < 0.05) than
vector transfectants. Histologically, xenograft tumors from cancer cells
expressing miR-137 were less proliferative (P < 0.05), partly due to inhibition
of EZH2 and LSD1 expression (P < 0.01) in both the transfected cancer cells and
tumors. Reporter assays indicated that miR-137 targets EZH2 and LSD1. These
results suggest that miR-137 is a tumor suppressor that is repressed in
endometrial cancer because the promoter of its gene becomes hypermethylated.
PMID- 29955088
TI - Arabidopsis mutants impaired in glutathione biosynthesis exhibit higher
sensitivity towards the glucosinolate hydrolysis product allyl-isothiocyanate.
AB - Upon tissue damage the plant secondary metabolites glucosinolates can generate
various hydrolysis products, including isothiocyanates (ITCs). Their role in
plant defence against insects and pest and their potential health benefits have
been well documented, but our knowledge regarding the endogenous molecular
mechanisms of their effect in plants is limited. Here we investigated the effect
of allyl-isothiocyanate (AITC) on Arabidopsis thaliana mutants impaired in
homeostasis of the low-molecular weight thiol glutathione. We show that
glutathione is important for the AITC-induced physiological responses, since
mutants deficient in glutathione biosynthesis displayed a lower biomass and
higher root growth inhibition than WT seedlings. These mutants were also more
susceptible than WT to another ITC, sulforaphane. Sulforaphane was however more
potent in inhibiting root growth than AITC. Combining AITC with the glutathione
biosynthesis inhibitor L-buthionine-sulfoximine (BSO) led to an even stronger
phenotype than observed for the single treatments. Furthermore, transgenic plants
expressing the redox-sensitive fluorescent biomarker roGFP2 indicated more
oxidative conditions during AITC treatment. Taken together, we provide genetic
evidence that glutathione plays an important role in AITC-induced growth
inhibition, although further studies need to be conducted to reveal the
underlying mechanisms.
PMID- 29955090
TI - Risk factors for dysphagia after a spinal cord injury: a systematic review and
meta-analysis.
AB - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To determine the
risk factors predictive of dysphagia after a spinal cord injury (SCI). SETTING:
None. METHODS: A comprehensive literature search was performed in five scientific
databases for English articles that identified risk factors for dysphagia after a
SCI in adult (>=19 years) individuals. Data extracted included: author name, year
and country of publication, participant demographics, sample size, study design,
method of dysphagia diagnosis, and risk factor percentages. Methodological
quality of studies was assessed using the Newcastle-Ottawa Scale. For identified
risk factors, risk percentages were transformed into risk ratios (RR) with 95%
confidence intervals. Quantitative synthesis was performed for risk factors
reported in two or more studies using restricted maximum-likelihood estimator
random effects models. RESULTS: Eleven studies met inclusion criteria of which
ten studies were of moderate quality (n = 10). Significant risk factors included:
age, injury severity, level of injury, presence of tracheostomy, coughing, voice
quality, bronchoscopy need, pneumonia, mechanical ventilation, nasogastric tubes,
comorbid injury, and a cervical surgery. Results of the quantitative synthesis
indicated that the presence of a tracheostomy posed a threefold greater risk of
the development of dysphagia (RR: 3.67); while, cervical surgery posed a 1.3
times greater risk of the development of dysphagia (RR: 1.30). CONCLUSIONS:
Knowledge of these risk factors can be a resource for clinicians in the early
diagnosis and appropriate medical management of dysphagia post SCI.
PMID- 29955089
TI - Energy expenditure and muscle activity during lying, sitting, standing, and
walking in people with motor-incomplete spinal cord injury.
AB - STUDY DESIGN: Cross-sectional exploratory study. OBJECTIVES: To determine oxygen
uptake (VO2), energy expenditure (EE), and muscle activity (MA) during lying
(rest), sitting, standing, and walking among ambulatory individuals with spinal
cord Injury (SCI) and to compare VO2, EE, and MA between individuals with
different levels of ambulation. SETTING: Rehabilitation institution with a spinal
cord injury unit. METHODS: A total of 22 adults with motor-incomplete SCI, ten in
a low-ambulation group (non-functional or household walker) and 12 in a high
ambulation group (community or normal walker). VO2 was measured using indirect
calorimetry. EE was expressed in metabolic equivalent of task (MET). MA was
measured using a wireless surface electromyography device. RESULTS: Mean VO2 was
3.19 ml/kg/min. During lying and sitting, EE was below 1.5 METs for all
participants. During standing, three participants of the low-ambulation group and
none in the high-ambulation group showed MET values of >1.5. In the walking
condition, all participants showed MET values above 1.5. MA during stance was
higher compared to the sitting condition and significantly higher in the low
ambulation group compared to the high-ambulation group. CONCLUSION: Lying,
supported- and unsupported sitting, without moving, appear to be sedentary
behaviors for ambulatory individuals with a motor-incomplete SCI (MET values of
<1.5 and a lack of MA). Walking, but not standing, is a moderate physical
activity (>1.5 METs), which can be used by all individuals with motor-incomplete
SCI to interrupt sedentary behavior.
PMID- 29955091
TI - Inducible Caspase9-mediated suicide gene for MSC-based cancer gene therapy.
AB - Cellular therapies based on mesenchymal stromal/stem cells (MSC) are promising
strategies in regenerative medicine and oncology. Despite encouraging results,
there is still some level of concerns on inoculating MSC in cancer patients. To
face this issue, one possibility resides in engineering MSC by incorporating a
suicide gene in order to control their fate once infused. Strategies based on
Herpes Simplex Virus Thymidine Kinase (HSV-TK) and the Cytosine Deaminase genes
have been developed and more recently a novel suicide gene, namely, iCasp9, has
been proposed. This approach is based on a variant of human Caspase9 that binds
with high affinity to a synthetic, bioinert small molecule (AP20187) leading to
cell death. Based on this technology so far marginally applied to MSC, we tested
the suitability of iCasp9 suicide strategy in MSC to further increase their
safety. MSC have been transfected by a lentiviral vector carrying iCasp9 gene and
then tested for viability after AP20187 treatment in comparison with mock
transfected cells. Moreover, accounting our anti-tumor approaches based on MSC
expressing potent anti-cancer ligand TNF-Related Apoptosis-Inducing Ligand
(TRAIL), we generated adipose MSC co-expressing iCasp9 and TRAIL successfully
targeting an aggressive sarcoma type. These data show that anti-cancer and
suicide mechanisms can coexist without affecting cells performance and hampering
the tumoricidal activity mediated by TRAIL. In conclusion, this study originally
indicates the suitability of combining a MSC-based anti-cancer gene approach with
iCasp9 demonstrating efficiency and specificity.
PMID- 29955092
TI - SFTA3 - a novel surfactant protein of the ocular surface and its role in corneal
wound healing and tear film surface tension.
AB - The study aimed to characterize the expression and function of SFTA3 at the
ocular surface and in tears. Ocular tissues, conjunctival (HCjE) and human
corneal (HCE) epithelial cell lines as well as tearfilm of patients suffering
from different forms of dry eye disease (DED) were analyzed by means of RT-PCR,
western blot, immunohistochemistry, and ELISA. A possible role of recombinant
SFTA3 in corneal wound healing was investigated performing in vitro scratch
assays. Tear film regulatory properties were analyzed with the spinning drop
method and the regulation of SFTA3 transcripts was studied in HCE and HCjE after
incubation with proinflammatory cytokines as well as typical ocular pathogens by
real-time RT-PCR and ELISA. The results reveal that human ocular tissue as well
as tears of healthy volunteers express SFTA3 whereas tears from patients with DED
showed significantly increased SFTA3 levels. In vitro wounding of HCE cell
cultures that had been treated with recombinant SFTA3 demonstrated a
significantly increased wound closure rate and rSFTA3 reduced the surface tension
of tear fluid. The results indicate that SFTA3 at the ocular surface seemed to be
involved in wound healing and the reduction of surface tension.
PMID- 29955093
TI - Live cell imaging reveals focal adhesions mechanoresponses in mammary epithelial
cells under sustained equibiaxial stress.
AB - Mechanical stimuli play a key role in many cell functions such as proliferation,
differentiation and migration. In the mammary gland, mechanical signals such as
the distension of mammary epithelial cells due to udder filling are proposed to
be directly involved during lactation and involution. However, the evolution of
focal adhesions -specialized multiprotein complexes that mechanically connect
cells with the extracellular matrix- during the mammary gland development, as
well as the influence of the mechanical stimuli involved, remains unclear. Here
we present the use of an equibiaxial stretching device for exerting a sustained
normal strain to mammary epithelial cells while quantitatively assessing cell
responses by fluorescence imaging techniques. Using this approach, we explored
changes in focal adhesion dynamics in HC11 mammary cells in response to a
mechanical sustained stress, which resembles the physiological stimuli. We
studied the relationship between a global stress and focal adhesion
assembly/disassembly, observing an enhanced persistency of focal adhesions under
strain as well as an increase in their size. At a molecular level, we evaluated
the mechanoresponses of vinculin and zyxin, two focal adhesion proteins
postulated as mechanosensors, observing an increment in vinculin molecular
tension and a slower zyxin dynamics while increasing the applied normal strain.
PMID- 29955094
TI - The Open Source GAITOR Suite for Rodent Gait Analysis.
AB - Locomotive changes are often associated with disease or injury, and these changes
can be quantified through gait analysis. Gait analysis has been applied to
preclinical studies, providing quantitative behavioural assessment with a
reasonable clinical analogue. However, available gait analysis technology for
small animals is somewhat limited. Furthermore, technological and analytical
challenges can limit the effectiveness of preclinical gait analysis. The Gait
Analysis Instrumentation and Technology Optimized for Rodents (GAITOR) Suite is
designed to increase the accessibility of preclinical gait analysis to
researchers, facilitating hardware and software customization for broad
applications. Here, the GAITOR Suite's utility is demonstrated in 4 models: a
monoiodoacetate (MIA) injection model of joint pain, a sciatic nerve injury
model, an elbow joint contracture model, and a spinal cord injury model. The
GAITOR Suite identified unique compensatory gait patterns in each model,
demonstrating the software's utility for detecting gait changes in rodent models
of highly disparate injuries and diseases. Robust gait analysis may improve
preclinical model selection, disease sequelae assessment, and evaluation of
potential therapeutics. Our group has provided the GAITOR Suite as an open
resource to the research community at www.GAITOR.org , aiming to promote and
improve the implementation of gait analysis in preclinical rodent models.
PMID- 29955095
TI - Assessment of the effect of climate changes in the Late Pleistocene and Holocene
on niche conservatism of an arvicolid specialist.
AB - Climate change is not only evident, but its implications on biodiversity are
already patent. The scientific community has delved into the limitations and
capabilities of species to face changes in climatic conditions through
experimental studies and, primarily, Species Distribution Models (SDMs).
Nevertheless, the widespread use of SDMs comes with some intrinsic assumptions,
such as niche conservatism, which are not always true. Alternatively, the fossil
record can provide additional data to solve the uncertainties of species'
responses to climate change based on their history. Using a combined
environmental (niche overlap indices) and geographical approach (temporal
transferability of SDMs), we assessed the niche conservatism of Microtus cabrerae
throughout its evolutionary history: the Late Pleistocene and the Holocene. The
set of analyses performed within this timeframe provides a broad view pointing to
a shift in the realized climatic niche of the species. Specifically, M. cabrerae
exhibited a broader niche during glacial times than interglacial times, expanding
towards novel conditions. Hence, the species might have developed an adaptive
ability, as a consequence of mechanisms of local adaptation or natural pressures,
or just be preadapted to cope with the novel environment, due to expansion into
an unfilled portion of the niche. Nevertheless, the more restricted realized
niche during last interglacial times reveals that the species could be close to
its physiological limits.
PMID- 29955096
TI - Increased food supply mitigates ocean acidification effects on calcification but
exacerbates effects on growth.
AB - Because many of the negative effects of ocean acidification on marine life may
result from underlying energetic short-falls associated with increased metabolic
demands, several studies have hypothesized that negative responses to high CO2
could be reduced by energy input. Although this hypothesis was supported by a
recent meta-analysis, we believe that the meta-analytic calculation used was not
appropriate to test the stated hypothesis. Here, we first clarify the hypothesis
put forward, the crux being that the effects of increased food supply and CO2
interact statistically. We then test this hypothesis by examining the available
data in a more appropriate analytical framework. Using factorial meta-analysis,
we confirm that food addition has a positive effect and CO2 has a negative effect
on both growth and calcification. For calcification, food addition did indeed
reduce CO2 impacts. Surprisingly, however, we found that food addition actually
exacerbated the effects of acidification on growth, perhaps due to increased
scope upon which CO2 effects can act in food-replete situations. These
interactive effects were undetectable using a multilevel meta-analytic approach.
Ongoing changes in food supply and carbonate chemistry, coupled with under
described, poorly understood, and potentially surprising interactive outcomes for
these two variables, suggest that the role of food should remain a priority in
ocean acidification research.Arising from: L. Ramajo et al., Sci. Rep. 6: 19374
(2016).
PMID- 29955097
TI - Publisher Correction: TGF-beta concentrations and activity are down-regulated in
the aqueous humor of patients with neovascular age-related macular degeneration.
AB - A correction to this article has been published and is linked from the HTML and
PDF versions of this paper. The error has not been fixed in the paper.
PMID- 29955098
TI - Changes in gene expression in Camelina sativa roots and vegetative tissues in
response to salinity stress.
AB - The response of Camelina sativa to salt stress was examined. Salt reduced shoot,
but not root length. Root and shoot weight were affected by salt, as was
photosynthetic capacity. Salt did not alter micro-element concentration in
shoots, but increased macro-element (Ca and Mg) levels. Gene expression patterns
in shoots indicated that salt stress may have led to shuttling of Na+ from the
cytoplasm to the tonoplast and to an increase in K+ and Ca+2 import into the
cytoplasm. In roots, gene expression patterns indicated that Na+ was exported
from the cytoplasm by the SOS pathway and that K+ was imported in response to
salt. Genes involved in chelation and storage were up-regulated in shoots, while
metal detoxification appeared to involve various export mechanisms in roots. In
shoots, genes involved in secondary metabolism leading to lignin, anthocyanin and
wax production were up-regulated. Partial genome partitioning was observed in
roots and shoots based on the expression of homeologous genes from the three C.
sativa sub-genomes. Sub-genome I and II were involved in the response to salinity
stress to about the same degree, while about 10% more differentially-expressed
genes were associated with sub-genome III.
PMID- 29955100
TI - Normal Mode Splitting in a Moving-Particles-Pumped Mechanical Oscillator: Clamped
Hinged Homogeneous Beam.
AB - The interaction of a mechanical oscillator with the operation actions and
environment fields will give rise to the splitting of normal modes. In this
study, we investigate the normal mode splitting behaviour of a moving-particles
pumped single-span clamped-hinged elastic homogeneous beam based on the proposed
multi-octave modal parametric oscillation model. Numerical experiments show the
entangled and squeezed oscillations of the phase-conjugated waves near the
resonance tongues. Theoretical analysis predicts the occurrence of multiple
simple resonances and the squeezing of the twin waves modal oscillation in the
region with a low speed of movement for the studied system.
PMID- 29955099
TI - Motility and chemotaxis of bacteria-driven microswimmers fabricated using antigen
43-mediated biotin display.
AB - Bacteria-driven biohybrid microswimmers (bacteriabots) combine synthetic cargo
with motile living bacteria that enable propulsion and steering. Although
fabrication and potential use of such bacteriabots have attracted much attention,
existing methods of fabrication require an extensive sample preparation that can
drastically decrease the viability and motility of bacteria. Moreover,
chemotactic behavior of bacteriabots in a liquid medium with chemical gradients
has remained largely unclear. To overcome these shortcomings, we designed
Escherichia coli to autonomously display biotin on its cell surface via the
engineered autotransporter antigen 43 and thus to bind streptavidin-coated cargo.
We show that the cargo attachment to these bacteria is greatly enhanced by
motility and occurs predominantly at the cell poles, which is greatly beneficial
for the fabrication of motile bacteriabots. We further performed a systemic study
to understand and optimize the ability of these bacteriabots to follow chemical
gradients. We demonstrate that the chemotaxis of bacteriabots is primarily
limited by the cargo-dependent reduction of swimming speed and show that the
fabrication of bacteriabots using elongated E. coli cells can be used to overcome
this limitation.
PMID- 29955101
TI - Kinked silicon nanowires-enabled interweaving electrode configuration for lithium
ion batteries.
AB - A tri-dimensional interweaving kinked silicon nanowires (k-SiNWs) assembly, with
a Ni current collector co-integrated, is evaluated as electrode configuration for
lithium ion batteries. The large-scale fabrication of k-SiNWs is based on a
procedure for continuous metal assisted chemical etching of Si, supported by a
chemical peeling step that enables the reuse of the Si substrate. The kinks are
triggered by a simple, repetitive etch-quench sequence in a HF and H2O2-based
etchant. We find that the inter-locking frameworks of k-SiNWs and multi-walled
carbon nanotubes exhibit beneficial mechanical properties with a foam-like
behavior amplified by the kinks and a suitable porosity for a minimal electrode
deformation upon Li insertion. In addition, ionic liquid electrolyte systems
associated with the integrated Ni current collector repress the detrimental
effects related to the Si-Li alloying reaction, enabling high cycling stability
with 80% capacity retention (1695 mAh/gSi) after 100 cycles. Areal capacities of
2.42 mAh/cm2 (1276 mAh/gelectrode) can be achieved at the maximum evaluated
thickness (corresponding to 1.3 mgSi/cm2). This work emphasizes the versatility
of the metal assisted chemical etching for the synthesis of advanced Si
nanostructures for high performance lithium ion battery electrodes.
PMID- 29955102
TI - Detection of small bunches of ions using image charges.
AB - A concept for detection of charged particles in a single fly-by, e.g. within an
ion optical system for deterministic implantation, is presented. It is based on
recording the image charge signal of ions moving through a detector, comprising a
set of cylindrical electrodes. This work describes theoretical and practical
aspects of image charge detection (ICD) and detector design and its application
in the context of real time ion detection. It is shown how false positive
detections are excluded reliably, although the signal-to-noise ratio is far too
low for time-domain analysis. This is achieved by applying a signal threshold
detection scheme in the frequency domain, which - complemented by the development
of specialised low-noise preamplifier electronics - will be the key to developing
single ion image charge detection for deterministic implantation.
PMID- 29955103
TI - Mechanism Underlying Green Discolouration of Myoglobin Induced by Atmospheric
Pressure Plasma.
AB - In this study, we elucidated the mechanism underlying atmospheric pressure plasma
(APP)-induced green discolouration of myoglobin. Green-coloured pigments are
produced upon conversion of myoglobin into sulphmyoglobin, choleglobin,
verdoheme, nitrihemin, or nitrimyoglobin. We exposed myoglobin dissolved in
phosphate buffer to APP for 20 min and found a decrease in a* value (+redness/
greenness) and increase in b* value (+yellowness/-blueness) (P < 0.05). In the
ultraviolet absorption spectrum, myoglobin treated with APP for 20 min showed
absorption peaks at 503 and 630 nm, a spectrum different from that of
sulphmyoglobin or choleglobin. The secondary structure and molecular weight of
myoglobin were unaffected by APP treatment, excluding the possibility of
verdoheme or nitrihemin formation. After APP treatment, nitrite was produced in
myoglobin solution that provided a positive environment for nitrimyoglobin
formation. However, the addition of 0.5% sodium dithionite, a strong reducing
agent, to myoglobin solution resulted in the formation of deoxymyoglobin, which
was subsequently converted to nitrosomyoglobin upon APP treatment to yield a
desirable red colour. Thus, APP-induced green colouration in myoglobin solution
is associated with nitrimyoglobin formation. The addition of the antioxidant
resulted in the production of red colour in myoglobin solution after APP
treatment owing to nitrosomyoglobin formation.
PMID- 29955104
TI - Targeting ARNT to attenuate renal fibrosis.
PMID- 29955105
TI - Genomic characterization of the RH locus detects complex and novel structural
variation in multi-ethnic cohorts.
AB - PURPOSE: Rh antigens can provoke severe alloimmune reactions, particularly in
high-risk transfusion contexts, such as sickle cell disease. Rh antigens are
encoded by the paralogs, RHD and RHCE, located in one of the most complex genetic
loci. Our goal was to characterize RH genetic variation in multi-ethnic cohorts,
with the focus on detecting RH structural variation (SV). METHODS: We customized
analytical methods to estimate paralog-specific copy number from next-generation
sequencing (NGS) data. We applied these methods to clinically characterized
samples, including four World Health Organization (WHO) genotyping references and
1135 Asian and Native American blood donors. Subsequently, we surveyed 1715
African American samples from the Jackson Heart Study. RESULTS: Most samples in
each dataset exhibited SV. SV detection enabled prediction of the immunogenic RhD
and RhC antigens in concordance (>99%) with serological phenotyping. RhC antigen
expression was associated with exon 2 hybrid alleles (RHCE*CE-D(2)-CE).
Clinically relevant exon 4-7 hybrid alleles (RHD*D-CE(4-7)-D) and exon 9 hybrid
alleles (RHCE*CE-D(9)-CE) were prevalent in African Americans. CONCLUSION: This
study shows custom NGS methods can accurately detect RH SV, and that SV is
important to inform prediction of relevant RH alleles. Additionally, this study
provides the first large NGS survey of RH alleles in African Americans.
PMID- 29955106
TI - Addressing the accuracy of direct-to-consumer genetic testing.
PMID- 29955107
TI - LONELINESS, CLOSENESS AND SHARED RESPONSIBILITY IN SUPERVISION.
AB - This paper examines the meaning of stepping in and out of the formal supervisory
roles and allowing relational unbidden experiences in the supervisory space. Such
episodes evolve the supervisory relationship because they help to relieve the
supervisees of their sense of aloneness in bearing a burdensome clinical
responsibility: they change the supervisees' perspective on therapeutic processes
from first person singular to first person plural. Despite their evaluative
function and the professional community that they share with supervisees,
supervisors can facilitate the emergence of these episodes with the widely
accepted practice of imagining therapeutic interactions. Such activity changes
the hierarchy and reduces the tension in the supervisory space, and allows
unbidden relational experiences to emerge. Thus, challenging the supervisory
framework and temporarily stepping out of the formal roles not only strengthens
the supervisees' ethical clinical position but also allows for productive and
creative processes in supervision.
PMID- 29955108
TI - Publisher Correction: Feeling stressed? It might be your T cells.
AB - In the version of this article initially published, the author surname citing the
linked article (Miyama) was incorrect in the seventh and eighth paragraphs. The
correct name is Miyajima.
PMID- 29955109
TI - Author Correction: A gammaherpesvirus provides protection against allergic asthma
by inducing the replacement of resident alveolar macrophages with regulatory
monocytes.
AB - In the version of this article initially published, the accession code for the
RNA-seq data set deposited in the NCBI public repository Sequence Read Archive
was missing from the 'Data availability' subsection of the Methods section. The
accession code is SRP125477.
PMID- 29955110
TI - Publisher Correction: Macrophages: damage control.
AB - In the version of this Research Highlight initially published, the url for the
linked article was incorrect ( https://doi.org/10.1172/JCI90647JCI90647 ). The
correct link is https://doi.org/10.1172/JCI90647 . The error has been corrected
in the HTML and PDF versions of the article.
PMID- 29955112
TI - Response to proposal for a novel cancer drug pricing model.
PMID- 29955111
TI - Interaction between the barley allelochemical compounds gramine and hordenine and
artificial lipid bilayers mimicking the plant plasma membrane.
AB - Some plants affect the development of neighbouring plants by releasing secondary
metabolites into their environment. This phenomenon is known as allelopathy and
is a potential tool for weed management within the framework of sustainable
agriculture. While many studies have investigated the mode of action of various
allelochemicals (molecules emitted by allelopathic plants), little attention has
been paid to their initial contact with the plant plasma membrane (PPM). In this
paper, this key step is explored for two alkaloids, gramine and hordenine, that
are allelochemicals from barley. Using in vitro bioassays, we first showed that
gramine has a greater toxicity than hordenine towards a weed commonly found in
northern countries (Matricaria recutita L.). Then, isothermal titration
calorimetry was used to show that these alkaloids spontaneously interact with
lipid bilayers that mimic the PPM. The greater impact of gramine on the
thermotropic behaviour of lipids compared to hordenine was established by means
of infrared spectroscopy. Finally, the molecular mechanisms of these interactions
were explored with molecular dynamics simulations. The good correlation between
phytotoxicity and the ability to disturb lipid bilayers is discussed. In this
study, biophysical tools were used for the first time to investigate the
interactions of allelochemicals with artificial PPM.
PMID- 29955113
TI - Reply to 'Response to proposal for a novel cancer drug pricing model'.
PMID- 29955114
TI - Synthetic lethal therapies for cancer: what's next after PARP inhibitors?
AB - The genetic concept of synthetic lethality has now been validated clinically
through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP)
inhibitors for the treatment of cancers in individuals with germline loss-of
function mutations in either BRCA1 or BRCA2. Three different PARP inhibitors have
now been approved for the treatment of patients with BRCA-mutant ovarian cancer
and one for those with BRCA-mutant breast cancer; these agents have also shown
promising results in patients with BRCA-mutant prostate cancer. Here, we describe
a number of other synthetic lethal interactions that have been discovered in
cancer. We discuss some of the underlying principles that might increase the
likelihood of clinical efficacy and how new computational and experimental
approaches are now facilitating the discovery and validation of synthetic lethal
interactions. Finally, we make suggestions on possible future directions and
challenges facing researchers in this field.
PMID- 29955115
TI - UGT1A1 polymorphisms associated with prolactin response in risperidone-treated
children and adolescents with autism spectrum disorder.
AB - The aim of this study was to investigate the association of drug-metabolizing
enzyme and transporter (DMET) polymorphisms with the risperidone-induced
prolactin response using an overlapping gene model between serum prolactin level
and hyperprolactinemia in autism spectrum disorder (ASD) patients. Eighty-four
ASD patients who were receiving risperidone for at least 1 month were recruited
and then assigned to either the normal prolactin group or the hyperprolactinemia
group based on their serum prolactin level. The genotype profile of 1936 (1931
single nucleotide polymorphisms (SNPs) and 5 copy number variation (CNVs) drug
metabolism markers was obtained using the Affymetrix DMET Plus GeneChip
microarray platform. Genotypes of SNPs used to test the accuracy of DMET genotype
profiling were determined using TaqMan SNP Genotyping Assay kits. Eighty-four
patients were selected for the allelic association study after microarray
analyses (51 in the normal prolactin group, and 33 in the hyperprolactinemia
group). An overlapping allelic association analysis of both analyses discovered
five DMET SNPs with a suggestive association (P < 0.05) with risperidone-induced
prolactin response. Three UGT1A1 SNPs (UGT1A1*80c.-364C > T, UGT1A1*93 c.-3156G >
A, and UGT1A1 c.-2950A > G, showed a suggestive association with the risperidone
induced prolactin response and found to be in complete linkage disequilibrium (D'
value of 1). In this DMET microarray platform, we found three UGT1A1 variants
with suggestive evidences of association with the risperidone-induced prolactin
response both measured by hyperprolactinemia and by prolactin level. However, due
to the lack of validation studies confirmation and further exploration are needed
in future pharmacogenomic studies.
PMID- 29955116
TI - Management of GERD: Are Potassium-Competitive Acid Blockers Superior to Proton
Pump Inhibitors?
PMID- 29955117
TI - Analyses of Bloody vs. Coffee-Grounds Hematemesis.
PMID- 29955118
TI - Hepatoptosis in a Patient with Alcoholic Hepatitis.
PMID- 29955119
TI - A Closer Look at Platelet Count and Prediction of Bleeding in Cirrhotic Patients.
PMID- 29955120
TI - Author Correction: Recurrent lower respiratory illnesses among young children in
rural Kyrgyzstan: overuse of antibiotics and possible under-diagnosis of asthma.
A qualitative FRESH AIR study.
AB - The original version of this Article contained an error in the spelling of the
author Mette Marie Kristensen, which was incorrectly given as Mette-Marie
Kristensen. The affiliation details for Mette Marie Kristensen were also
incorrect in this Article. This has now been corrected in both the PDF and HTML
versions of this article.
PMID- 29955121
TI - From rock 'n' roll to heavy metal.
PMID- 29955122
TI - Livers from Venus and livers from Mars.
PMID- 29955123
TI - The impact of the Deepwater Horizon blowout on historic shipwreck-associated
sediment microbiomes in the northern Gulf of Mexico.
AB - More than 2,000 historic shipwrecks spanning 500 years of history, rest on the
Gulf of Mexico seafloor. Shipwrecks serve as artificial reefs and hotspots of
biodiversity by providing hard substrate, something rare in deep ocean regions.
The Deepwater Horizon (DWH) spill discharged crude oil into the deep Gulf.
Because of physical, biological, and chemical interactions, DWH oil was deposited
on the seafloor, where historic shipwrecks are present. This study examined
sediment microbiomes at seven historic shipwrecks. Steel-hulled, World War II-era
shipwrecks and wooden-hulled, 19th century shipwrecks within and outside of the
surface oiled area and subsurface plume were examined. Analysis of 16S rRNA
sequence libraries, sediment radiocarbon age data, sedimentation rates, and
hydrocarbons revealed that the German U-boat U-166 and the wooden-hulled sailing
vessel known as the Mardi Gras Wreck, both in the Mississippi Canyon leasing
area, were exposed to deposited oil during a rapid sedimentation event. Impacts
to shipwreck microbiomes included a significant increase in Piscirickettsiaceae
related sequences in surface sediments, and reduced biodiversity relative to
unimpacted sites. This study is the first to address the impact of the spill on
shipwreck-associated microbiomes, and to explore how shipwrecks themselves
influence microbiome diversity in the deep sea.
PMID- 29955124
TI - Enhanced PAPSS2/VCAN sulfation axis is essential for Snail-mediated breast cancer
cell migration and metastasis.
AB - The zinc finger protein Snail is a master regulator of epithelial-mesenchymal
transition (EMT) and a strong inducer of tumor metastasis, yet the signal
cascades triggered by Snail have not been completely revealed. Here, we report
the discovery of the sulfation program that can be induced by Snail in breast
cancer cells, and which plays an essential role in cell migration and metastasis.
Specifically, Snail induces the expression of PAPSS2, a gene that encodes a rate
limiting enzyme in sulfation pathway, and VCAN, a gene that encodes the
chondroitin sulfate proteoglycan Versican in multiple breast cancer cells.
Depletion of PAPSS2 in MCF7 and MDA-MB-231 cells results in reduced cell
migration, while overexpression of PAPSS2 promotes cell migration. Moreover, MDA
MB-231-shPAPSS2 cells display a significantly lower rate of lung metastasis and
lower number of micrometastatic nodules in nude mice, and conversely, MDA-MB-231
PAPSS2 cells increase lung metastasis. Similarly, depletion of VCAN dampens the
cell migration activity induced by Snail or PAPSS2 in MCF 10A cells. Moreover,
PAPSS inhibitor sodium chlorate effectively decreases cell migration induced by
Snail and PAPSS2. More importantly, the expression of Snail, PAPSS2, and VCAN is
positively correlated in breast cancer tissues. Together, these findings are
important for understanding the genetic programs that control tumor metastasis
and may identify previously undetected therapeutic targets to treat metastatic
disease.
PMID- 29955125
TI - FHL3 links cell growth and self-renewal by modulating SOX4 in glioma.
AB - Differentiation status significantly affects the properties of malignant glioma
cells, with non-stem cells inducing tumor enlargement and stem-like cells driving
tumor initiation and treatment resistance. It is not completely understood how
the same protein can have a distinct role in these cell populations. Here, we
report that four and a half LIM domain protein 3 (FHL3) has an inhibitory effect
on proliferation in non-stem glioma cells and a non-proliferative effect in
glioma stem cells (GSCs). In GSCs, we show that FHL3 interacts with the Smad2/3
protein complex at the SOX4 promoter region, inhibits SOX4 transcriptional
activity by recruiting PPM1A phosphatase to Smad2/3, and then suppresses GSC
tumor sphere formation and self-renewal in vitro and in vivo via downregulation
of SOX2 expression. Altogether, these findings highlight the role of FHL3 as a
stemness-suppressor in regulation of the Smad2/3-SOX4-SOX2 axis in glioma.
PMID- 29955126
TI - Location, location, location.
PMID- 29955127
TI - Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating
diabetic foot ulcers healing in rats.
AB - Diabetic ischemic ulcer is an intractable diabetic complication. Angiogenesis is
a critical factor for wound healing in patients with diabetic foot wounds.
Sustained gene delivery could be notably necessary in modulating gene expression
in chronic ulcer healing and might be a promising approach for diabetic foot
ulcers. In the present study, Sprague-Dawley rats were used to establish diabetic
foot ulcer models by streptozotocin and skin biopsy punch. The plasmids
expressing VEGF-A and PDGF-B were prepared and then incorporated with polylactic
co-glycolic acid (PLGA) nanospheres to upregulate genes expression. The aim of
this study was to explore whether the engineered VEGF-A and PDGF-B based plasmid
loaded nanospheres could be upregulated in streptozotocin-induced diabetic rats
and improve the wound healing. The cultured fibroblasts could be effectively
transfected by means of nanosphere/plasmid in vitro. In vivo, the expression of
VEGF-A and PDGF-B was significantly upregulated at full-thickness foot dorsal
skin wounds and the area of ulceration was progressively and significantly
reduced following treatment with nanosphere/plasmid. These results indicated that
combined gene transfer of VEGF-A and PDGF-B could improve reparative processes in
the wounded skin of diabetic rats and nanosphere may be a potential non-viral
vector for gene therapy of the diabetic foot ulcer.
PMID- 29955128
TI - Evidence- and consensus-based recommendations for phlebotomy in polycythemia
vera.
PMID- 29955129
TI - So-called "blast phase" of chronic myelomonocytic leukemia: a plea for uniform
terminology.
PMID- 29955130
TI - LRPAP1 is a frequent proliferation-inducing antigen of BCRs of mantle cell
lymphomas and can be used for specific therapeutic targeting.
AB - The predominant usage of VH4-34 and V3-21 and reports of stereotyped CDR3s
suggest a shared antigenic target of B-cell receptors (BCR) from mantle cell
lymphomas (MCL). To identify the target antigens of MCL-BCRs, BCRs from 21
patients and seven MCL cell lines were recombinantly expressed and used for
antigen screening. The BCRs from 8/21 patients and 2/7 MCL cell lines reacted
specifically with the autoantigen low-density lipoprotein receptor-related
protein-associated protein 1 (LRPAP1). High-titered and light chain-restricted
anti-LRPAP1 serum antibodies were found in MCL patients, but not in controls.
LRPAP1 induced proliferation by BCR pathway activation, while an LRPAP1-ETA'
toxin-conjugate specifically killed MCL cells with LRPAP1-specific BCRs. Our
results suggest a role of LRPAP1 in lymphomagenesis and maintenance of a
considerable proportion of MCL cases by chronic autoantigenic stimulation, likely
evolving from a chronic autoreactive B-cell response. Importantly, LRPAP1 can be
used for a novel therapeutic approach that targets MCL with LRPAP1-reactive BCRs
with high specificity.
PMID- 29955131
TI - Dnmt1 links BCR-ABLp210 to epigenetic tumor stem cell priming in myeloid
leukemia.
PMID- 29955132
TI - An MDS-derived cell line and a series of its sublines serve as an in vitro model
for the leukemic evolution of MDS.
PMID- 29955133
TI - Integrative analysis of oncogenic fusion genes and their functional impact in
colorectal cancer.
AB - BACKGROUND: Fusion genes are good candidates of molecular targets for cancer
therapy. However, there is insufficient research on the clinical implications and
functional characteristics of fusion genes in colorectal cancer (CRC). METHODS:
In this study, we analysed RNA sequencing data of CRC patients (147 tumour and 47
matched normal tissues) to identify oncogenic fusion genes and evaluated their
role in CRC. RESULTS: We validated 24 fusion genes, including novel fusions, by
three algorithms and Sanger sequencing. Fusions from most patients were mutually
exclusive CRC oncogenes and included tumour suppressor gene mutations. Eleven
fusion genes from 13 patients (8.8%) were determined as oncogenic fusion genes by
analysing their gene expression and function. To investigate their oncogenic
impact, we performed proliferation and migration assays of CRC cell lines
expressing fusion genes of GTF3A-CDK8, NAGLU- IKZF3, RNF121- FOLR2, and STRN-ALK.
Overexpression of these fusion genes increased cell proliferation except GTF3A
CDK8. In addition, overexpression of NAGLU-IKZF3 enhanced migration of CRC cells.
We demonstrated that NAGLU-IKZF3, RNF121-FOLR2, and STRN-ALK had tumourigenic
effects in CRC. CONCLUSION: In summary, we identified and characterised oncogenic
fusion genes and their function in CRC, and implicated NAGLU-IKZF3 and RNF121
FOLR2 as novel molecular targets for personalised medicine development.
PMID- 29955134
TI - Characterisation of tumour microvessel density during progression of high-grade
serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study).
AB - BACKGROUND: High-grade serous ovarian cancer (HGSOC) intratumoural vasculature
evolution remains unknown. The study investigated changes in tumour microvessel
density (MVD) in a large cohort of paired primary and recurrent HGSOC tissue
samples and its impact on patients' clinico-pathological outcome. METHODS: A
total of 222 primary (pOC) and recurrent (rOC) intra-patient paired HGSOC were
assessed for immunohistochemical expression of angiogenesis-associated biomarkers
(CD31, to evaluate MVD, and VEGF-A). Expression profiles were compared between
pOCs and rOCs and correlated with patients' data. RESULTS: High intratumoural MVD
and VEGF-A expression were observed in 75.7% (84/111) and 20.7% (23/111) pOCs,
respectively. MVDhigh and VEGF(+) samples were detected in 51.4% (57/111) and
20.7% (23/111) rOCs, respectively. MVDhigh/VEGF(+) co-expression was found in
19.8% (22/111) and 8.1% (9/111) of pOCs and rOCs, respectively (p = 0.02).
Pairwise analysis showed no significant change in MVD (p = 0.935) and VEGF-A (p =
0.121) levels from pOCs to rOCs. MVDhigh pOCs were associated with higher CD3(+)
(p = 0.029) and CD8(+) (p = 0.013) intratumoural effector TILs, while VEGF(+)
samples were most frequently encountered among BRCA-mutated tumours (p = 0.019).
Multivariate analysis showed VEGF and MVD were not independent prognostic factors
for OS. CONCLUSIONS: HGSOC intratumoural vasculature did not undergo significant
changes during disease progression. High concentration of CD31(+) vessels seems
to promote recruitment of effector TILs. The study also provides preliminary
evidence of the correlation between VEGF-positivity and BRCA status.
PMID- 29955135
TI - Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck
squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE
012.
AB - BACKGROUND: Second-line treatment options for advanced head and neck squamous
cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the
safety and the efficacy of pembrolizumab for the treatment of HNSCC after long
term follow-up. METHODS: Multi-centre, non-randomised trial included two HNSCC
cohorts (initial and expansion) in which 192 patients were eligible. Patients
received pembrolizumab 10 mg/kg every 2 weeks (initial cohort; N = 60) or 200 mg
every 3 weeks (expansion cohort; N = 132). Co-primary endpoints were safety and
overall response rate (ORR; RECIST v1.1; central imaging vendor review). RESULTS:
Median follow-up was 9 months (range, 0.2-32). Treatment-related adverse events
(AEs) of any grade and grade 3/4 occurred in 123 (64%) and 24 (13%) patients,
respectively. No deaths were attributed to treatment-related AEs. ORR was 18%
(34/192; 95% CI, 13-24%). Median response duration was not reached (range, 2+ to
30+ months); 85% of responses lasted >=6 months. Overall survival at 12 months
was 38%. CONCLUSIONS: Some patients received 2 years of treatment and the
responses were ongoing for more than 30 months; the durable anti-tumour activity
and tolerable safety profile, observed with long-term follow-up, support the use
of pembrolizumab as a treatment for recurrent/metastatic HNSCC.
PMID- 29955136
TI - A randomised phase II study of second-line XELIRI regimen versus irinotecan
monotherapy in advanced biliary tract cancer patients progressed on gemcitabine
and cisplatin.
AB - BACKGROUND: The majority of advanced biliary tract cancer (ABTC) patients will
progress after gemcitabine and cisplatin (GP) doublet therapy, while the standard
second-line regimen has not been established. We conducted this study to assess
the efficacy and safety of second-line irinotecan and capecitabine (XELIRI)
regimen vs. irinotecan monotherapy in ABTC patients progressed on GP. METHODS:
Sixty-four GP refractory ABTC patients were randomised to either irinotecan 180
mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1-10 of a 14-day
cycle (XELIRI-arm) or single-agent irinotecan 180 mg/m2 on day 1 of a 14-day
cycle (IRI-arm). Treatments were repeated until disease progression or
unacceptable toxicity occurred. RESULTS: A total of 60 patients were included in
the analysis. For XELIRI and IRI-arms, respectively, the median PFS was 3.7 vs.
2.4 months, 9-month survival rate 60.9% vs. 32.0%, median OS 10.1 vs. 7.3 months,
and disease control rate 63.3% vs. 50.0%. The most common grade 3 or 4 toxicities
were leucopaenia and neutropaenia. CONCLUSIONS: This randomised, phase II study
of irinotecan-containing regimens in good PS second-line ABTC patients showed a
clear benefit of XELIRI regimen over irinotecan monotherapy in prolonging PFS,
with acceptable toxicity.
PMID- 29955137
TI - Downregulation of WNT11 is associated with bladder tissue fibrosis in patients
with interstitial cystitis/bladder pain syndrome without Hunner lesion.
AB - This study assessed the functional role of WNT genes and the association between
WNT signalling cascades and fibrosis in interstitial cystitis/bladder pain
syndrome (IC/BPS) patients. Twenty-five patients (3 males, 22 females; mean age
59.7 +/- 10.9 years), included 7 non-Hunner-type IC (NHIC), 18 Hunner-type IC
(HIC), and 5 non-IC (control) groups. The expression of sonic hedgehog, WNT gene
family, and genes previously reported as biomarkers for IC/BPS were examined
using RT-PCR in biopsy specimens from the mucosa and submucosa layer of the
bladder. WNT2B, WNT5A, WNT10A, and WNT11 functions in the urothelium were
evaluated by silencing in an HBlEpC cell line. Pelvic Pain and Urgency/Frequency
Patient Symptom Scale scores, O'Leary-Sant Symptom and Problem Index scores, and
Visual Analogue Scores did not differ between the NHIC and HIC groups. However,
HIC patients had significantly shorter symptom duration (30.9 vs 70.8 months, p =
0.046), higher daily urinary frequency (16.1 versus 8.5 times, p = 0.006), and
smaller bladder capacity (208.6 versus 361.4 ml, p = 0.006) than NHIC patients.
Overall WNT gene expression was lower in NHIC than HIC patients. Bladder
epithelial tissues from HIC patients were characterised by the downregulation of
WNT11. Silencing of WNT11, WNT2B, WNT5A, and WNT10A in HBlEpCs resulted in
fibrotic changes, indicated by fibrotic morphology, increased fibrosis-related
gene expression, and nuclear localisation of phosphorylated SMAD2, and increased
vimentin and fibronectin levels. Downregulation of WNT11 results in fibrotic
changes of bladder epithelial cells and is associated with the pathogenesis and
differential diagnosis of NHIC. Decreased expression of WNT11 is a potential
biomarker for predicting NHIC.
PMID- 29955138
TI - Risk of Infection and Sepsis in Pediatric Patients with Traumatic Brain Injury
Admitted to Hospital Following Major Trauma.
AB - Head injury accounts for 29% of all traumatic deaths in children. Sepsis is
significantly associated with an increased risk of mortality in adult traumatic
brain injury patients. In the pediatric population, this relationship is not well
understood. The objective of this study was to compare the proportion of
pediatric traumatic brain injury (TBI) patients and trauma patients without brain
injury (NTBI) who developed sepsis or any infection during their index hospital
admission. We performed a retrospective study of all trauma patients <18 years of
age, admitted to trauma centres in Alberta, Canada from January 1, 2003 to
December 31, 2012. Patients who died within 24 hrs of trauma (n = 147) and those
with burns as the primary mechanism of injury (n = 53) were excluded. Hospital
admission data for the remaining 2556 patients was analyzed. 1727 TBI patients
and 829 NTBI patients were included. TBI was associated with lower odds of
developing sepsis (OR 0.32 95% CI 0.14-0.77 p = 0.011). TBI was not found to be
independently associated with developing any infectious complication after
adjusting for confounding by Injury Severity Score (OR 1.25 95% CI 0.90-1.74 p =
0.180). These relationships warrant further study.
PMID- 29955139
TI - Methanotrophy across a natural permafrost thaw environment.
AB - The fate of carbon sequestered in permafrost is a key concern for future global
warming as this large carbon stock is rapidly becoming a net methane source due
to widespread thaw. Methane release from permafrost is moderated by
methanotrophs, which oxidise 20-60% of this methane before emission to the
atmosphere. Despite the importance of methanotrophs to carbon cycling, these
microorganisms are under-characterised and have not been studied across a natural
permafrost thaw gradient. Here, we examine methanotroph communities from the
active layer of a permafrost thaw gradient in Stordalen Mire (Abisko, Sweden)
spanning three years, analysing 188 metagenomes and 24 metatranscriptomes paired
with in situ biogeochemical data. Methanotroph community composition and activity
varied significantly as thaw progressed from intact permafrost palsa, to
partially thawed bog and fully thawed fen. Thirteen methanotroph population
genomes were recovered, including two novel genomes belonging to the uncultivated
upland soil cluster alpha (USCalpha) group and a novel potentially methanotrophic
Hyphomicrobiaceae. Combined analysis of porewater delta13C-CH4 isotopes and
methanotroph abundances showed methane oxidation was greatest below the oxic
anoxic interface in the bog. These results detail the direct effect of thaw on
autochthonous methanotroph communities, and their consequent changes in
population structure, activity and methane moderation potential.
PMID- 29955141
TI - Comparison of melanoma gene expression score with histopathology, fluorescence in
situ hybridization, and SNP array for the classification of melanocytic
neoplasms.
AB - While most melanomas can be distinguished from nevi by histopathology, the
histology is ambiguous for some melanocytic tumors, contributing to diagnostic
uncertainty. Therefore molecular assays, including FISH or SNP array, and more
recently a gene expression test (myPath, Myriad Genetics) have been proposed to
aid in the work-up of ambiguous tumors. Two hundred and sixty-eight prospectively
submitted cases were gathered, with the goal of comparing the myPath assay to
morphologic diagnosis in (1) morphologically unequivocal cases (198), and to
morphologic diagnosis and FISH in (2) morphologically ambiguous cases (70).
Melanoma FISH was performed using probes for 6p25, 6q23, 11q13, Cep6, 9p21, and
Cep9 and scored according to established criteria. The myPath assay was scored by
the manufacturer as benign, indeterminate, or malignant. In the unequivocal
group, myPath assay showed 75% agreement with morphologic diagnosis, with 67%
sensitivity and 81% specificity. In the ambiguous group, FISH and myPath showed
69% inter-test agreement. For these cases agreement with histopathologic
interpretation was 84% for FISH and 74% for myPath. Sensitivity and specificity
of FISH was 61 and 100%, 50 and 93% for myPath, respectively. Cases from both
groups in which myPath was discordant with either morphologic diagnosis and/or
FISH (81/268 cases), were submitted for evaluation by two experienced
dermatopathologist and also by SNP-array. SNP-array results correlated better
than FISH, which correlated better than myPath, with the morphologic
interpretation. Our findings document that molecular diagnostics show good
correlation with consensus diagnoses, but discordant results occur, and vary in
level of correlation with consensus interpretations. Studies with long-term
outcomes data within specific ambiguous lesion subsets are required to establish
the accuracy of this test, as each molecular diagnostic technique has limitations
based on both lack of clinical outcomes data in ambiguous melanocytic tumors and
in terms of their sensitivity and specificity in melanocytic lesion subtypes.
PMID- 29955140
TI - Factors influencing bacterial microbiome composition in a wild non-human primate
community in Tai National Park, Cote d'Ivoire.
AB - Microbiomes impact a variety of processes including a host's ability to access
nutrients and maintain health. While host species differences in microbiomes have
been described across ecosystems, little is known about how microbiomes assemble,
particularly in the ecological and social contexts in which they evolved. We
examined gut microbiome composition in nine sympatric wild non-human primate
(NHP) species. Despite sharing an environment and interspecific interactions,
individuals harbored unique and persistent microbiomes influenced by host
species, social group, and parentage, but surprisingly not by social
relationships among members of a social group. We found a branching order of host
species networks constructed using the composition of their microbiomes as
characters, which was incongruent with known NHP phylogenetic relationships, with
chimpanzees (Pan troglodytes verus) sister to colobines, upon which they
regularly prey. In contrast to phylogenetic clustering found in all monkey
microbiomes, chimpanzee microbiomes were unique in that they exhibited patterns
of phylogenetic overdispersion. This reflects unique ecological processes
impacting microbiome composition in chimpanzees and future studies will elucidate
the aspects of chimpanzee ecology, life history, and physiology that explain
their unique microbiome community structure. Our study of contemporaneous
microbiomes of all sympatric diurnal NHP in an ecosystem highlights the diverse
dispersal routes shaping these complex communities.
PMID- 29955142
TI - Thioredoxin-interacting protein is an independent risk stratifier for breast
ductal carcinoma in situ.
AB - Current clinicopathological parameters are useful predictors of breast ductal
carcinoma in situ behavior, but they are insufficient to define high-risk
patients for disease progression precisely. Thioredoxin-interacting protein
(TXNIP) is a key player of oxidative stress. This study aims to evaluate the role
of TXNIP as a predictor of ductal carcinoma in situ progression. Tissue
microarrays from 776 pure ductal carcinoma in situ and 239 mixed ductal carcinoma
in situ and invasive tumors were constructed. All patients were treated at a
single institution with a long-term follow-up and TXNIP expression was assessed
using immunohistochemistry. TXNIP expression was investigated in terms of
associations with clinicopathological and molecular features and patient outcome.
Loss/reduced cytoplasmic expression of TXNIP was associated with features of
aggressiveness including high nuclear grade (p = 1.6 * 10-5), presence of comedo
necrosis (p = 0.001), and estrogen receptor negative (ER-)/HER2- ductal carcinoma
in situ (p = 4.6 * 10-5). Univariate analysis showed an inverse association
between TXNIP expression and outcome in terms of shorter local recurrence-free
survival (p = 0.009). Multivariable analyses showed that independent predictors
of ductal carcinoma in situ recurrence were low TXNIP expression (p = 0.005, HR =
0.51, and 95% CI: 0.32-0.81), larger ductal carcinoma in situ size, and high
nuclear grade. TXNIP functions as a tumor suppressor gene with loss of its
expression associated with ductal carcinoma in situ recurrence. TXNIP can be used
as a potentially useful marker in prognostic stratification of ductal carcinoma
in situ for management decisions.
PMID- 29955144
TI - Validation of a targeted next-generation sequencing approach to detect mismatch
repair deficiency in colorectal adenocarcinoma.
AB - Mismatch repair protein deficiency is a hallmark of cancers associated with Lynch
syndrome and is a biomarker for response to immunotherapy. With the increasing
adoption of cancer next-generation sequencing, there has been a movement to
develop screening approaches that take advantage of the unique mutational
signatures of mismatch repair-deficient tumors. Here, we develop a sequencing
based metric that distinguishes mismatch repair-deficient from mismatch repair
proficient colorectal adenocarcinomas with comparison to immunohistochemical
staining. We find that a single criterion of three or more single base pair
insertion or deletion mutations per megabase sequenced, occurring in
mononucleotide repeat regions of four or more nucleotides, is sufficient to
detect mismatch repair deficiency with 96% sensitivity and 100% specificity in a
training set of 241 cancers and 96% sensitivity and 99% specificity in a
validation set of 436 additional cancers. Using data from the same cohort, we
also find that sequencing information from only three genes-ARID1A, KMT2D, and
SOX9-is sufficient to detect mismatch repair-deficient colorectal adenocarcinomas
with 76% sensitivity and 98% specificity in the validation set. These findings
support the notion that targeted next-generation sequencing already being
performed for clinical or research purposes can also be used to accurately detect
mismatch repair deficiency in colorectal adenocarcinomas.
PMID- 29955143
TI - Refinement of high-risk endometrial cancer classification using DNA damage
response biomarkers: a TransPORTEC initiative.
AB - The TransPORTEC consortium previouslclassified high-risk endometrial cancer
including poor-risk histologies such as clear cells, into four molecular subtypes
"POLE mutated," "microsatellite unstable," "TP53 mutated," and "no specific
molecular profile." We evaluated whether DNA damage response biomarkers could
further refine this high-risk tumors classification, in particular the
heterogeneous "no specific molecular profile" and "TP53 mutated" subsets recently
qualified as poor prognosis in high-risk endometrial cancer. DNA damage response
biomarkers including proteins involved in DNA damage (delta-H2AX), homologous
recombination (RAD51), regulators of error-prone Non Homologous End-Joining (DNA
pk, FANCD2), and PARP-1 were evaluated in 116 high-risk tumors by
immunohistochemistry. CD8 and PD-1 expression by immunochemistry and mutation
analyses were performed previously. Survival outcome were calculated using Kaplan
Meier and Log-rank test. None of the DNA damage response biomarkers alone were
prognostic. However markers were informative within molecular subsets. Among the
"no specific molecular profile" subset, delta-H2AX+ was significantly predictive
of poor disease free survival (Hazard Ratio = 2.56; p = 0.026), and among "TP53
mutated," a DNA-pk+/FANCD2- profile (favouring error-prone Non Homologous End
Joining) predicted worst disease free survival (Hazard Ratio = 4.95; p = 0.009)
resulting in five distinct prognostic subgroups from best to worst prognosis:
group1 "POLE mutated/Microsatellite unstable" > group2 "no specific molecular
profile with no DNA damage" > group3 "TP53 mutated/Non Homologous End-Joining
negative" > group4 "no specific molecular profile with high DNA damage" > group5
"TP53 mutated/Non Homologous End-Joining positive"; p = 0.0002). Actionable
targets were also different among subsets. Group3 had significantly higher
infiltration of PD-1+ immune cells (p = 0.003), segregating with group1. Group2
had frequent PI3K pathway mutations and ER positivity. While group5, with the
worst prognosis, had high DNA damage and PARP-1 expression providing a rationale
for PARP inhibition. Our findings have refined the TransPORTEC prognostic
classification of high-risk endometrial cancer into five distinct subgroups by
integrating DNA damage response biomarkers and identified molecular subtype
specific therapeutic strategies.
PMID- 29955145
TI - Detection of a MicroRNA molecular signature of ultraviolet radiation in the
superficial regions of melanocytic nevi on sun-exposed skin.
AB - How melanocytes transform into melanoma cells remains largely unknown. However,
prolonged ultraviolet radiation exposure is linked with melanoma, and the DNA of
melanomas arising in chronically sun-exposed skin is characterized by an elevated
number of pyrimidine transitions, mainly C>T (predominantly caused by ultraviolet
B), and transversions of GC>TA or AT>CG (caused by ultraviolet A over indirect
mechanisms). Since ultraviolet penetrates mostly only the superficial dermis, we
sought to determine the extent to which superficial and deep melanocytes of nevi
in sun-exposed skin differ in their miRNA expression and consider the changes as
likely secondary to ultraviolet radiation-induced damage. The differentially
expressed miRNAs were analyzed for known potential oncomiRs or linked to
potential oncogenes or tumor suppressors. Superficial and deep melanocytes were
microdissected from the nevi of 14 patients. The suspensions were processed for
hybridization to a ribonucleotide protection system with 2280 total probes,
including 2256 miRNA probes targeting 2083 human miRNAs. A comprehensive analysis
of all human miRNAs registered in miRBase 11.0 was performed using the HTG
Molecular Diagnostic database. Statistical analysis of these data yielded for 14
samples a statistically relevant profile of 39 miRNA species at FDR<0.1 that were
differentially expressed between superficial and deep melanocytes. Ingenuity
Pathway Analysis based on the expression data of these 39 miRNAs suggested the
gene transcripts AR, MDM2, SMAD2/3, and YBX1 as the most probable miRNA targets,
which were validated at the protein level. Our findings suggest that superficial
ultraviolet radiation-damaged melanocytes can be differentiated from deep
melanocytes on the basis of the expression of 39 miRNAs, the most probable gene
transcript and protein targets of which are AR, MDM2, SMAD2/3, and YBX1, with
YBX1 expression validating the best the molecular signature in
immunohistochemical analysis.
PMID- 29955146
TI - Clinicopathologic and molecular features in hairy cell leukemia-variant: single
institutional experience.
AB - Hairy cell leukemia-variant is rare. Only a small number of cases have been
reported in the literature with little cytogenetic or molecular data available.
In this study, we describe the clinicopathologic and genetic features of 23
patients with hairy cell leukemia-variant (16 men and 7 women) with a median age
of 70 years. Most patients had splenomegaly (90%), leukocytosis (77%), and
lymphocytosis (82%); no patients had monocytopenia. Histologically, the bone
marrow biopsy specimens showed a mixed pattern of predominantly interstitial and
lesser intrasinusoidal infiltration by leukemic cells. In bone marrow aspirate
smears most cells had villous cytoplasmic features and a small nucleolus. We
describe unusual sites of hairy cell leukemia-variant involvement in 4 patients,
including brain, omentum, terminal ileum, and skin at the time of initial
presentation. Immunophenotyping showed monotypic B-cells positive for pan B-cell
antigens, CD11c, and CD103, and negative for CD25 and annexin A1. Conventional
cytogenetic or fluorescence in situ hybridization analysis showed deletions of
17p13/TP53 and 11q22/ATM gene in 5/12 (42%) and 2/9 (22%) cases, respectively.
Sequencing of the variable region of IGVH showed mutations (>2% deviation from
germline) in 40% of the cases assessed. MAP2K1 mutation (p.C121S) was seen in 1
of 14 (7%) patients tested. No BRAF V600E mutations were detected. The patients
were treated in a heterogeneous manner, but most often with therapies designed
for classical hairy cell leukemia and the 5-year overall survival was 84%. In
summary, hairy cell leukemia-variant exhibits a heterogeneous spectrum of
clinical, morphologic, immunophenotypic, and genetic features that may overlap
with classic hairy cell leukemia and other hairy cell-like B-cell neoplasms. A
subset of patients can have an aggressive clinical course. In our experience
MAP2K1 mutations are uncommon in this disease.
PMID- 29955148
TI - Assessing colorectal cancer mismatch repair status in the modern era: a survey of
current practices and re-evaluation of the role of microsatellite instability
testing.
AB - Results of DNA mismatch repair testing are used to detect Lynch syndrome and have
prognostic and therapeutic implications among patients with sporadic colorectal
carcinomas. Immunohistochemistry for mismatch repair proteins (MLH1, PMS2, MSH2,
MSH6) and PCR for microsatellite instability are two established methods for
assessing mismatch repair function. Older literature suggested a discordance rate
of approximately 5% between these assays, leading some institutions to perform
dual testing on all cases. Although universal mismatch repair testing is now
recommended by multiple professional organizations, none provide guidelines
regarding preferred assays. We surveyed 96 academic and nonacademic institutions
to assess Lynch syndrome screening practices and evaluated discordance rates
between immunohistochemistry and PCR among 809 colorectal cancers tested in our
own institution. Our survey demonstrated no significant differences between
academic and nonacademic practices with respect to testing strategies. Eighty six
percent performed universal screening, and usually (76%) employed
immunohistochemistry on initial biopsy samples. Only 20% employed PCR; these were
mostly academic practices that used both immunohistochemistry and PCR (p < 0.01
compared with the nonacademic groups). Loss of MLH1/PMS2 staining was often (90%)
followed by either BRAF mutational analysis or MLH1 methylation assays. Only 24%
adhered to WHO recommendations to assign histologic grade based on mismatch
repair status. We found only 3 cases (0.4%) with discordant immunohistochemistry
and PCR results in our own practice: 1 reflected decreased MSH-6 staining in a
neoadjuvantly treated microsatellite stable tumor, 1 MLH1-deficient tumor showed
diminished MLH1/PMS2 in the tumor compared with internal control, and 1 case
reflected an error in the molecular laboratory. Overall, our results showed
extremely low discordance between methods assessing mismatch repair status and
would suggest immunohistochemistry as the preferred single screening test. PCR
can be reserved for cases that show equivocal immunostaining patterns.
PMID- 29955147
TI - Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without
PDGFB fusions.
AB - Dermatofibrosarcoma protuberans is underlined by recurrent collagen type I alpha
1 chain-platelet-derived growth factor B chain (COL1A1-PDGFB) fusions but ~ 4% of
typical dermatofibrosarcoma protuberans remain negative for this translocation in
routine molecular screening. We investigated a series of 21 cases not associated
with the pathognomonic COL1A1-PDGFB fusion on routine fluorescence in situ
hybridization (FISH) testing. All cases displayed morphological and clinical
features consistent with the diagnosis of dermatofibrosarcoma protuberans. RNA
sequencing analysis was successful in 20 cases. The classical COL1A1-PDGFB fusion
was present in 40% of cases (n = 8/20), and subsequently confirmed with a COL1A1
break-apart FISH probe in all but one case (n = 7/8). 55% of cases (n = 11/20)
displayed novel PDGFD rearrangements; PDGFD being fused either to the 5' part of
COL6A3 (2q37.3) (n = 9/11) or EMILIN2 (18p11) (n = 2/11). All rearrangements led
to in-frame fusion transcripts and were confirmed at genomic level by FISH and/or
array-comparative genomic hybridization. PDGFD-rearranged dermatofibrosarcoma
protuberans presented clinical outcomes similar to typical dermatofibrosarcoma
protuberans. Notably, the two EMILIN2-PDGFD cases displayed fibrosarcomatous
transformation and homozygous deletions of CDKN2A at genomic level. We report the
first recurrent molecular variant of dermatofibrosarcoma protuberans involving
PDGFD, which functionally mimic bona fide COL1A1-PDGFB fusions, leading
presumably to a similar autocrine loop-stimulating PDGFRB. This study also
emphasizes that COL1A1-PDGFB fusions can be cytogenetically cryptic on FISH
testing in a subset of cases, thereby representing a diagnostic pitfall that
pathologists should be aware of.
PMID- 29955149
TI - Saccharomyces cerevisiae-like 1 (SEC14L1) is a prognostic factor in breast cancer
associated with lymphovascular invasion.
AB - Lymphovascular invasion is strongly related to breast cancer metastasis. However,
the underlying mechanisms of lymphovascular invasion and its driver molecules in
breast cancer remain to be defined. In this study, we explore differential
expression of genes in large molecularly characterized and clinically annotated
datasets of invasive breast cancer patients (n = 8056) coupled with histological
review and strict definition for lymphovascular invasion status. The METABRIC
series was used to identify genes associated with lymphovascular invasion, as
defined using hematoxylin and eosin staining supplemented by
immunohistochemistry, at the genomic/transcriptomic levels. Saccharomyces
cerevisiae-like 1 (SEC14L1) was identified as one of the most significant genes
associated with lymphovascular invasion. The prognostic significance of SEC14L1
gene copy number and mRNA expression was further investigated in the METABRIC
series and externally validated using the Breast Cancer Gene-Expression Miner
v4.0. Protein expression of SEC14L1 was also assessed using immunohistochemistry
in series of early stage breast cancer using tissue microarrays. SEC14L1 gene
copy number gain was significantly associated with high histological grade and
poor outcome. SEC14L1 mRNA expression showed positive association with higher
grade, lymph node metastasis, and poor outcome. SEC14L1 protein overexpression
was significantly associated with lymphovascular invasion (p < 0.0001), higher
grade (p = 0.011), HER2 positivity (p = 0.036), and shorter survival (p =
0.00075). Our findings specify SEC14L1 as an independent prognostic factor in
breast cancer. Its association, at both transcriptome and protein expression
levels, with lymphovascular invasion and outcome could imply an important role in
tumor progression. A further mechanistic insight into its molecular roles
including potential therapeutic utility is warranted.
PMID- 29955151
TI - Pretreatment and early-treatment cortical thickness is associated with SSRI
treatment response in major depressive disorder.
AB - To date, there are no biomarkers for major depressive disorder (MDD) treatment
response in clinical use. Such biomarkers could allow for individualized
treatment selection, reducing time spent on ineffective treatments and the burden
of MDD. In search of such a biomarker, multisite pretreatment and early-treatment
(1 week into treatment) structural magnetic resonance (MR) images were acquired
from 184 patients with MDD randomized to an 8-week trial of the selective
serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents
a large, multisite, placebo-controlled effort to examine the association between
pretreatment differences or early-treatment changes in cortical thickness and
treatment-specific outcomes. For standardization, a novel, robust site
harmonization procedure was applied to structural measures in a priori regions
(rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle
frontal, and hippocampus), chosen based on previously published reports.
Pretreatment cortical thickness or volume did not significantly associate with
SSRI response. Thickening of the rostral anterior cingulate cortex in the first
week of treatment was associated with better 8-week responses to SSRI (p =
0.010). These findings indicate that frontal lobe structural alterations in the
first week of treatment may be associated with long-term treatment efficacy.
While these associational findings may help to elucidate the specific neural
targets of SSRIs, the predictive accuracy of pretreatment or early-treatment
structural alterations in classifying treatment remitters from nonremitters was
limited to 63.9%. Therefore, in this large sample of adults with MDD, structural
MR imaging measures were not found to be clinically translatable biomarkers of
treatment response to SSRI or placebo.
PMID- 29955152
TI - Publisher Correction: Inference of ecological and social drivers of human brain
size evolution.
AB - In the PDF version of this Letter, Andy Gardner was originally listed as a
corresponding author, instead of Mauricio Gonzalez-Forero. This has been
corrected online.
PMID- 29955153
TI - Publisher Correction: An increase in the 12C + 12C fusion rate from resonances at
astrophysical energies.
AB - In equation (1) of this Letter, the closing bracket was missing; in Extended Data
Fig. 1 and the accompanying legend, 'Phi(pd)' should have been 'Phi2(pd)', and in
the Methods the text "Odd J assignments are uncertain by +/-1." has been added.
These errors have all been corrected online.
PMID- 29955154
TI - Mental template matching is a potential cultural transmission mechanism for New
Caledonian crow tool manufacturing traditions.
AB - Cumulative cultural evolution occurs when social traditions accumulate
improvements over time. In humans cumulative cultural evolution is thought to
depend on a unique suite of cognitive abilities, including teaching, language and
imitation. Tool-making New Caledonian crows show some hallmarks of cumulative
culture; but this claim is contentious, in part because these birds do not appear
to imitate. One alternative hypothesis is that crows' tool designs could be
culturally transmitted through a process of mental template matching. That is,
individuals could use or observe conspecifics' tools, form a mental template of a
particular tool design, and then reproduce this in their own manufacture - a
process analogous to birdsong learning. Here, we provide the first evidence
supporting this hypothesis, by demonstrating that New Caledonian crows have the
cognitive capacity for mental template matching. Using a novel manufacture
paradigm, crows were first trained to drop paper into a vending machine to
retrieve rewards. They later learnt that only items of a particular size (large
or small templates) were rewarded. At test, despite being rewarded at random, and
with no physical templates present, crows manufactured items that were more
similar in size to previously rewarded, than unrewarded, templates. Our results
provide the first evidence that this cognitive ability may underpin the
transmission of New Caledonian crows' natural tool designs.
PMID- 29955150
TI - Inflaming sex differences in mood disorders.
AB - Men and women often experience different symptoms or rates of occurrence for a
variety of mood disorders. Many of the symptoms of mood disorders overlap with
autoimmune disorders, which also have a higher prevalence in women. There is a
growing interest in exploring the immune system to provide biomarkers for
diagnosis of mood disorders, along with new targets for developing treatments.
This review examines known sex differences in the immune system and their
relationship to mood disorders. We focus on immune alterations associated with
unipolar depression, bipolar depression, and anxiety disorders. We describe work
from both basic and clinical research examining potential immune mechanisms
thought to contribute to stress susceptibility and associated mood disorders. We
propose that sex and age are important, intertwined factors that need to be
included in future experimental designs if we are going to harness the power of
the immune system to develop a new wave of treatments for mood disorders.
PMID- 29955155
TI - The role of sentrin-specific protease 2 substrate recognition in TGF-beta-induced
tumorigenesis.
AB - Smad4, a common-mediator of Smads, plays a central role in forming complexes with
receptor-phosphorylated Smads, and then transduces transforming growth factor
(TGF)-beta signals into the nuclei. Although many cellular factors are involved
in TGF-beta induced epithelial-to-mesenchymal transition (EMT) and cell
migration, very little is known with the mechanism of Smad4 regulation on pro
oncogenes response by TGF-beta. Herein, we demonstrate the interaction of Sentrin
specific protease 2 (SENP2) with Smad4 through SENP2 residue 363~400. The same
segment is also important for desumoylation of Smad4, and able to relieve
sumoylation-mediated TGF-beta repression. The SENP2363~400 segment is critical
for TGF-beta-induced cell migration, which is correlated with SENP2363~400
deletion mutant failed to increase matrix metalloproteinase (MMP)-9 and EMT
marker gene expression. Moreover, our results suggest that the interaction and
desumoylation between SENP2 and Smad4 promote cell migration in triple-negative
breast cancer cells. Altogether, our data show how SENP2 regulates its substrate
for desumoylation, and also the role of SENP2 in TGF-beta induced cancer cell
migration.
PMID- 29955156
TI - Optimal integration of actions and their visual effects is based on both online
and prior causality evidence.
AB - The brain needs to identify redundant sensory signals in order to integrate them
optimally. The identification process, referred to as causal inference, depends
on the spatial and temporal correspondence of the incoming sensory signals
('online sensory causality evidence') as well as on prior expectations regarding
their causal relation. We here examine whether the same causal inference process
underlies spatial integration of actions and their visual consequences. We used a
basic cursor-control task for which online sensory causality evidence is provided
by the correlated hand and cursor movements, and prior expectations are formed by
everyday experience of such correlated movements. Participants made out-and-back
movements and subsequently judged the hand or cursor movement endpoints. In one
condition, we omitted the online sensory causality evidence by showing the cursor
only at the movement endpoint. The integration strength was lower than in
conditions where the cursor was visible during the outward movement, but a
substantial level of integration persisted. These findings support the hypothesis
that the binding of actions and their visual consequences is based on the general
mechanism of optimal integration, and they specifically show that such binding
can occur even if it is previous experience only that identifies the action
consequence.
PMID- 29955157
TI - Ingestible biosensors for gastrointestinal diagnosis.
PMID- 29955158
TI - GTP-binding facilitates EB1 recruitment onto microtubules by relieving its auto
inhibition.
AB - Microtubule plus end-binding protein, EB1 is a key regulator of microtubule
dynamics. Auto-inhibitory interaction in EB1 has previously been shown to inhibit
its ability to bind to microtubules and regulate microtubule dynamics. However,
the factors that promote its microtubule regulatory activity by over-coming the
auto-inhibition are less known. Here, we show that GTP plays a critical role in
promoting the microtubule-targeting activity of EB1 by suppressing its auto
inhibition. Our biophysical data demonstrate that GTP binds to EB1 at a distinct
site in its conserved N-terminal domain. Detailed analyses reveal that GTP
binding suppresses the intra-molecular inhibitory interaction between the
globular N-terminus and the C-terminal coiled-coil domain. We further show that
mutation of the GTP-binding site residues in N-terminus weakens the affinity for
GTP, but also for the C-terminus, indicating overlapping binding sites. Confocal
imaging and biochemical analysis reveal that EB1 localization on the microtubules
is significantly increased upon mutations of the GTP-binding site residues. The
results demonstrate a unique role of GTP in facilitating EB1 interaction with the
microtubules by relieving its intra-molecular inhibition. They also implicate
that GTP-binding may regulate the functions of EB1 on the cellular microtubules.
PMID- 29955160
TI - Sample-to-Answer Droplet Magnetofluidic Platform for Point-of-Care Hepatitis C
Viral Load Quantitation.
AB - Gold standard quantitative nucleic acid tests for diagnosis of viral diseases are
currently limited to implementation in laboratories outside of the clinic. An
instrument for conducting nucleic acid testing at the point-of-care (POC) that is
easily operable by the clinician would reduce the required number of visits to
the clinic and improve patient retention for proper treatment. Here we present a
droplet magnetofluidic (DM) platform, which leverages functionalized magnetic
particles to miniaturize and automate laboratory assays for use in the clinic at
the POC. Our novel thermoformed disposable cartridge coupled to a portable
multiaxial magnetofluidic instrument enables real-time PCR assays for
quantitative and sensitive detection of nucleic acids from crude biosamples.
Instead of laborious benchtop sample purification techniques followed by elution
and spiking into PCR buffer, the user simply injects the biosample of interest
into a cartridge with magnetic particles and loads the cartridge into the
instrument. We demonstrate the utility of our platform with hepatitis C virus
(HCV) RNA viral load quantitation from blood serum in approximately 1 hour.
Clinical serum samples (n = 18) were directly processed on cartridges with no
false positives and a limit of detection of 45 IU per 10 ul sample injection.
PMID- 29955159
TI - Unsupervised CT Lung Image Segmentation of a Mycobacterium Tuberculosis Infection
Model.
AB - Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis
that produces pulmonary damage. Radiological imaging is the preferred technique
for the assessment of TB longitudinal course. Computer-assisted identification of
biomarkers eases the work of the radiologist by providing a quantitative
assessment of disease. Lung segmentation is the step before biomarker extraction.
In this study, we present an automatic procedure that enables robust segmentation
of damaged lungs that have lesions attached to the parenchyma and are affected by
respiratory movement artifacts in a Mycobacterium Tuberculosis infection model.
Its main steps are the extraction of the healthy lung tissue and the airway tree
followed by elimination of the fuzzy boundaries. Its performance was compared
with respect to a segmentation obtained using: (1) a semi-automatic tool and (2)
an approach based on fuzzy connectedness. A consensus segmentation resulting from
the majority voting of three experts' annotations was considered our ground
truth. The proposed approach improves the overlap indicators (Dice similarity
coefficient, 94% +/- 4%) and the surface similarity coefficients (Hausdorff
distance, 8.64 mm +/- 7.36 mm) in the majority of the most difficult-to-segment
slices. Results indicate that the refined lung segmentations generated could
facilitate the extraction of meaningful quantitative data on disease burden.
PMID- 29955161
TI - Effect of intranasal oxytocin on the core social symptoms of autism spectrum
disorder: a randomized clinical trial.
AB - Although small-scale studies have described the effects of oxytocin on social
deficits in autism spectrum disorder (ASD), no large-scale study has been
conducted. In this randomized, parallel-group, multicenter, placebo-controlled,
double-blind trial in Japan, 106 ASD individuals (18-48 y.o.) were enrolled
between Jan 2015 and March 2016. Participants were randomly assigned to a 6-week
intranasal oxytocin (48IU/day, n = 53) or placebo (n = 53) group. One-hundred
three participants were analyzed. Since oxytocin reduced the primary endpoint,
Autism Diagnostic Observation Schedule (ADOS) reciprocity, (from 8.5 to 7.7; P <
.001) but placebo also reduced the score (8.3 to 7.2; P < .001), no between-group
difference was found (effect size -0.08; 95% CI, -0.46 to 0.31; P = .69);
however, plasma oxytocin was only elevated from baseline to endpoint in the
oxytocin-group compared with the placebo-group (effect size -1.12; -1.53 to
0.70; P < .0001). Among the secondary endpoints, oxytocin reduced ADOS repetitive
behavior (2.0 to 1.5; P < .0001) compared with placebo (2.0 to 1.8; P = .43)
(effect size 0.44; 0.05 to 0.83; P = .026). In addition, the duration of gaze
fixation on socially relevant regions, another secondary endpoint, was increased
by oxytocin (41.2 to 52.3; P = .03) compared with placebo (45.7 to 40.4; P = .25)
(effect size 0.55; 0.10 to 1.0; P = .018). No significant effects were observed
for the other secondary endpoints. No significant difference in the prevalence of
adverse events was observed between groups, although one participant experienced
temporary gynecomastia during oxytocin administration. Based on the present
findings, we cannot recommend continuous intranasal oxytocin treatment alone at
the current dose and duration for treatment of the core social symptoms of high
functioning ASD in adult men, although this large-scale trial suggests oxytocin's
possibility to treat ASD repetitive behavior.
PMID- 29955162
TI - Endogenous opioid system dysregulation in depression: implications for new
therapeutic approaches.
AB - The United States is in the midst of an opioid addiction and overdose crisis
precipitated and exacerbated by use of prescription opioid medicines. The
majority of opioid prescriptions are dispensed to patients with comorbid mood
disorders including major depressive disorder (MDD). A growing body of research
indicates that the endogenous opioid system is directly involved in the
regulation of mood and is dysregulated in MDD. This involvement of the endogenous
opioid system may underlie the disproportionate use of opioids among patients
with mood disorders. Emerging approaches to address endogenous opioid
dysregulation in MDD may yield novel therapeutics that have a low or absent risk
of abuse and addiction relative to u-opioid agonists. Moreover, agents targeting
the endogenous opioid system would be expected to yield clinical benefits
qualitatively different from conventional monaminergic antidepressants. The
development of safe and effective agents to treat MDD-associated endogenous
opioid dysregulation may represent a distinct and currently underappreciated
means of addressing treatment resistant depression with the potential to
attenuate the on-going opioid crisis.
PMID- 29955163
TI - Molecular windows into the human brain for psychiatric disorders.
AB - Delineating the pathophysiology of psychiatric disorders has been extremely
challenging but technological advances in recent decades have facilitated a
deeper interrogation of molecular processes in the human brain. Initial candidate
gene expression studies of the postmortem brain have evolved into genome wide
profiling of the transcriptome and the epigenome, a critical regulator of gene
expression. Here, we review the potential and challenges of direct molecular
characterization of the postmortem human brain, and provide a brief overview of
recent transcriptional and epigenetic studies with respect to neuropsychiatric
disorders. Such information can now be leveraged and integrated with the growing
number of genome-wide association databases to provide a functional context of
trait-associated genetic variants linked to psychiatric illnesses and related
phenotypes. While it is clear that the field is still developing and challenges
remain to be surmounted, these recent advances nevertheless hold tremendous
promise for delineating the neurobiological underpinnings of mental diseases and
accelerating the development of novel medication strategies.
PMID- 29955164
TI - Autism-specific maternal autoantibodies produce behavioral abnormalities in an
endogenous antigen-driven mouse model of autism.
AB - Immune dysregulation has been noted consistently in individuals with autism
spectrum disorder (ASD) and their families, including the presence of
autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of
children with ASD versus <1% in mothers of typically developing children. Our lab
recently identified the peptide epitope sequences on seven antigenic proteins
targeted by these maternal autoantibodies. Through immunization with these
peptide epitopes, we have successfully created an endogenous, antigen-driven
mouse model that ensures a constant exposure to the salient autoantibodies
throughout gestation in C57BL/6J mice. This exposure more naturally mimics what
is observed in mothers of children with ASD. Male and female offspring were
tested using a comprehensive sequence of behavioral assays, as well as measures
of health and development highly relevant to ASD. We found that MAR-ASD male and
female offspring had significant alterations in development and social
interactions during dyadic play. Although 3-chambered social approach was not
significantly different, fewer social interactions with an estrous female were
noted in the adult male MAR-ASD animals, as well as reduced vocalizations emitted
in response to social cues with robust repetitive self-grooming behaviors
relative to saline treated controls. The generation of MAR-ASD-specific epitope
autoantibodies in female mice prior to breeding created a model that demonstrates
for the first time that ASD-specific antigen-induced maternal autoantibodies
produced alterations in a constellation of ASD-relevant behaviors.
PMID- 29955165
TI - Rediscovering the value of families for psychiatric genetics research.
AB - As it is likely that both common and rare genetic variation are important for
complex disease risk, studies that examine the full range of the allelic
frequency distribution should be utilized to dissect the genetic influences on
mental illness. The rate limiting factor for inferring an association between a
variant and a phenotype is inevitably the total number of copies of the minor
allele captured in the studied sample. For rare variation, with minor allele
frequencies of 0.5% or less, very large samples of unrelated individuals are
necessary to unambiguously associate a locus with an illness. Unfortunately, such
large samples are often cost prohibitive. However, by using alternative analytic
strategies and studying related individuals, particularly those from large
multiplex families, it is possible to reduce the required sample size while
maintaining statistical power. We contend that using whole genome sequence (WGS)
in extended pedigrees provides a cost-effective strategy for psychiatric gene
mapping that complements common variant approaches and WGS in unrelated
individuals. This was our impetus for forming the "Pedigree-Based Whole Genome
Sequencing of Affective and Psychotic Disorders" consortium. In this review, we
provide a rationale for the use of WGS with pedigrees in modern psychiatric
genetics research. We begin with a focused review of the current literature,
followed by a short history of family-based research in psychiatry. Next, we
describe several advantages of pedigrees for WGS research, including power
estimates, methods for studying the environment, and endophenotypes. We conclude
with a brief description of our consortium and its goals.
PMID- 29955166
TI - Treatment strategies for ADHD: an evidence-based guide to select optimal
treatment.
AB - Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing
disorder affecting children, adolescents, and adults. Several treatment
strategies are available that can successfully ameliorate symptoms, ranging from
pharmacological to dietary interventions. Due to the increasing range of
available options, an informed selection or prioritization of treatments is
becoming harder for clinicians. This review aims to provide an evidence-based
appraisal of the literature on ADHD treatment, supplemented by expert opinion on
plausibility. We outline proposed mechanisms of action of established
pharmacologic and non-pharmacologic treatments, and we review targets of novel
treatments. The most relevant evidence supporting efficacy and safety of each
treatment strategy is discussed. We review the individualized features of the
patient that should guide the selection of treatments in a shared decision-making
continuum. We provide guidance for optimizing initiation of treatment and follow
up of patients in clinical settings.
PMID- 29955167
TI - Striatal Rgs4 regulates feeding and susceptibility to diet-induced obesity.
AB - Consumption of high fat, high sugar (western) diets is a major contributor to the
current high levels of obesity. Here, we used a multidisciplinary approach to
gain insight into the molecular mechanisms underlying susceptibility to diet
induced obesity (DIO). Using positron emission tomography (PET), we identified
the dorsal striatum as the brain area most altered in DIO-susceptible rats and
molecular studies within this region highlighted regulator of G-protein signaling
4 (Rgs4) within laser-capture micro-dissected striatonigral (SN) and
striatopallidal (SP) medium spiny neurons (MSNs) as playing a key role. Rgs4 is a
GTPase accelerating enzyme implicated in plasticity mechanisms of SP MSNs, which
are known to regulate feeding and disturbances of which are associated with
obesity. Compared to DIO-resistant rats, DIO-susceptible rats exhibited increased
striatal Rgs4 with mRNA expression levels enriched in SP MSNs. siRNA-mediated
knockdown of striatal Rgs4 in DIO-susceptible rats decreased food intake to
levels comparable to DIO-resistant animals. Finally, we demonstrated that the
human Rgs4 gene locus is associated with increased body weight and obesity
susceptibility phenotypes, and that overweight humans exhibit increased striatal
Rgs4 protein. Our findings highlight a novel role for involvement of Rgs4 in SP
MSNs in feeding and DIO-susceptibility.
PMID- 29955169
TI - Author Correction: Dynamic actuation of glassy polymersomes through isomerization
of a single azobenzene unit at the block copolymer interface.
AB - In the version of this Article originally published, multiple changes to the
"Results and discussion" section were required. In paragraph 1, "(Supplementary
Fig. 1)" should have read "(Fig. 1e-j and Supplementary Fig. 1)"; in the first
sentence of paragraph 3, "(R6G)" should have read "(R6G, Fig. 2i)"; in paragraph
6 in the sentence beginning "Temporal release of hydrophilic...", Supplementary
Fig. 4 should have been cited after "360 nm"; in paragraph 9, in the sentence
beginning "To test this...", "Fig. 4e" should have read "Fig. 4a"; in paragraph
10, in the sentence beginning "When the irradiation...", "(Fig. 4a-d)" should
have read "(Fig. 4d,e)"; in paragraph 11, in the sentence beginning "Pristine
PLA", "P1" should have read "P2"; and in the penultimate paragraph, in the
sentence beginning "Moreover, a control PEG-PLA...", "block copolymer" should
have been followed by (P5); Fig. 4g should have been Fig. 4c; "hydrophobic
azobenzene small molecules" should have been followed by (12); and Fig. 4f should
have been Fig. 4b. Finally, Supplementary Videos 1 and 2 were missing from the
Article. All of these corrections have been made to the online versions.
PMID- 29955168
TI - xMD-miRNA-seq to generate near in vivo miRNA expression estimates in colon
epithelial cells.
AB - Accurate, RNA-seq based, microRNA (miRNA) expression estimates from primary cells
have recently been described. However, this in vitro data is mainly obtained from
cell culture, which is known to alter cell maturity/differentiation status,
significantly changing miRNA levels. What is needed is a robust method to obtain
in vivo miRNA expression values directly from cells. We introduce expression
microdissection miRNA small RNA sequencing (xMD-miRNA-seq), a method to isolate
cells directly from formalin fixed paraffin-embedded (FFPE) tissues. xMD-miRNA
seq is a low-cost, high-throughput, immunohistochemistry-based method to capture
any cell type of interest. As a proof-of-concept, we isolated colon epithelial
cells from two specimens and performed low-input small RNA-seq. We generated up
to 600,000 miRNA reads from the samples. Isolated epithelial cells, had abundant
epithelial-enriched miRNA expression (miR-192; miR-194; miR-200b; miR-200c; miR
215; miR-375) and overall similar miRNA expression patterns to other epithelial
cell populations (colonic enteroids and flow-isolated colon epithelium). xMD
derived epithelial cells were generally not contaminated by other adjacent cells
of the colon as noted by t-SNE analysis. xMD-miRNA-seq allows for simple,
economical, and efficient identification of cell-specific miRNA expression
estimates. Further development will enhance rapid identification of cell-specific
miRNA expression estimates in health and disease for nearly any cell type using
archival FFPE material.
PMID- 29955170
TI - Transmission ratio distortion is frequent in Arabidopsis thaliana controlled
crosses.
AB - The equal probability of transmission of alleles from either parent during sexual
reproduction is a central tenet of genetics and evolutionary biology. Yet, there
are many cases where this rule is violated. The preferential transmission of
alleles or genotypes is termed transmission ratio distortion (TRD). Examples of
TRD have been identified in many species, implying that they are universal, but
the resolution of species-wide studies of TRD are limited. We have performed a
species-wide screen for TRD in over 500 segregating F2 populations of Arabidopsis
thaliana using pooled reduced-representation genome sequencing. TRD was evident
in up to a quarter of surveyed populations. Most populations exhibited distortion
at only one genomic region, with some regions being repeatedly affected in
multiple populations. Our results begin to elucidate the species-level
architecture of biased transmission of genetic material in A. thaliana, and serve
as a springboard for future studies into the biological basis of TRD in this
species.
PMID- 29955171
TI - Adaptive responses along a depth and a latitudinal gradient in the endemic
seagrass Posidonia oceanica.
AB - Seagrass meadows provide important ecosystem services and are critical for the
survival of the associated invertebrate community. However, they are threatened
worldwide by human-driven environmental change. Understanding the seagrasses'
potential for adaptation is critical to assess not only their ability to persist
under future global change scenarios, but also to assess the persistence of the
associated communities. Here we screened a wild population of Posidonia oceanica,
an endemic long-lived seagrass in the Mediterranean Sea, for genes that may be
target of environmental selection, using an outlier and a genome-wide
transcriptome analysis. We identified loci where polymorphism or differential
expression was associated with either a latitudinal or a bathymetric gradient, as
well as with both gradients in an effort to identify loci associated with
temperature and light. We found the candidate genes underlying growth and
immunity to be divergent between populations adapted to different latitudes
and/or depths, providing evidence for local adaptation. Furthermore, we found
evidence of reduced gene flow among populations including adjacent populations.
Reduced gene flow, combined with low sexual recombination, small effective
population size, and long generation time of P. oceanica raises concerns for the
long-term persistence of this species, especially in the face of rapid
environmental change driven by human activities.
PMID- 29955174
TI - Targeting the cytoskeleton in heart failure.
PMID- 29955173
TI - Project MinE: study design and pilot analyses of a large-scale whole-genome
sequencing study in amyotrophic lateral sclerosis.
AB - The most recent genome-wide association study in amyotrophic lateral sclerosis
(ALS) demonstrates a disproportionate contribution from low-frequency variants to
genetic susceptibility to disease. We have therefore begun Project MinE, an
international collaboration that seeks to analyze whole-genome sequence data of
at least 15 000 ALS patients and 7500 controls. Here, we report on the design of
Project MinE and pilot analyses of successfully sequenced 1169 ALS patients and
608 controls drawn from the Netherlands. As has become characteristic of
sequencing studies, we find an abundance of rare genetic variation (minor allele
frequency < 0.1%), the vast majority of which is absent in public datasets.
Principal component analysis reveals local geographical clustering of these
variants within The Netherlands. We use the whole-genome sequence data to explore
the implications of poor geographical matching of cases and controls in a
sequence-based disease study and to investigate how ancestry-matched, externally
sequenced controls can induce false positive associations. Also, we have publicly
released genome-wide minor allele counts in cases and controls, as well as
results from genic burden tests.
PMID- 29955175
TI - An altered CD8+ T cell epitope of insulin prevents type 1 diabetes in humanized
NOD mice.
AB - Autoreactive CD8+ T cells, which play an indispensable role in beta cell
destruction, represent an emerging target for the prevention of type 1 diabetes
(T1D). Altered peptide ligands (APLs) can efficiently induce antigen-specific T
cells anergy, apoptosis or shifts in the immune response. Here, we found that HLA
A*0201-restricted CD8+ T cell responses against a primary beta-cell autoantigen
insulin epitope InsB15-14 were present in both NOD.beta2mnull.HHD NOD mice and
T1D patients. We generated several APL candidates for InsB15-14 by residue
substitution at the p6 position. Only H6F exhibited an inhibitory effect on
mInsB15-14-specific CD8+ T cell responses in vitro. H6F treatment significantly
reduced the T1D incidence, which was accompanied by diminished autoreactive CD8+
T cell responses to mInsB15-14, inhibited infiltration of CD8+ and CD4+ T cells
in the pancreas and reduced pro-inflammatory cytokine production in pancreatic
and splenic T cells in NOD.beta2mnull.HHD mice. Mechanistically, H6F treatment
significantly augmented a tiny portion of CD8+CD25+Foxp3+ T cells in the spleen
and especially in the pancreas. This subset exhibited typical Treg phenotypes and
required peptide-specific restimulation to exert immunosuppressive activity.
Therefore, this APL H6F may be a promising candidate with potential clinical
application value for antigen-specific prevention of T1D.
PMID- 29955172
TI - Primary brain calcification: an international study reporting novel variants and
associated phenotypes.
AB - Primary familial brain calcification (PFBC) is a rare cerebral microvascular
calcifying disorder with a wide spectrum of motor, cognitive, and
neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant
trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and
XPR1. Our study aimed at screening the coding regions of these genes in a series
of 177 unrelated probands that fulfilled the diagnostic criteria for primary
brain calcification regardless of their family history. Sequence variants were
classified as pathogenic, likely pathogenic, or of uncertain significance (VUS),
based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying
either pathogenic or likely pathogenic variants (n = 34, 19.2%) or VUS (n = 11,
6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and
PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were
symptomatic and the most recurrent symptoms were parkinsonism, cognitive
impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic
individuals, respectively), with a wide range of age at onset (from childhood to
81 years). While the pathogenic and likely pathogenic variants identified in this
study can be used for genetic counseling, the VUS will require additional
evidence, such as recurrence in unrelated patients, in order to be classified as
pathogenic.
PMID- 29955176
TI - Subfunctionalization versus neofunctionalization after whole-genome duplication.
PMID- 29955177
TI - Heritable influences on the mind and brain.
PMID- 29955179
TI - Reply to: 'Subfunctionalization versus neofunctionalization after whole-genome
duplication'.
PMID- 29955178
TI - Genome-scale analysis identifies paralog lethality as a vulnerability of
chromosome 1p loss in cancer.
AB - Functional redundancy shared by paralog genes may afford protection against
genetic perturbations, but it can also result in genetic vulnerabilities due to
mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and
CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and
MAGOHB, core members of the splicing-dependent exon junction complex, as top
ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with
hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due
to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context
compromises viability by globally perturbing alternative splicing and RNA
surveillance. Dependency on IPO13, an importin-beta receptor that mediates
nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with
dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies
in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH
and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a
rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p
deletion.
PMID- 29955180
TI - Using an atlas of gene regulation across 44 human tissues to inform complex
disease- and trait-associated variation.
AB - We apply integrative approaches to expression quantitative loci (eQTLs) from 44
tissues from the Genotype-Tissue Expression project and genome-wide association
study data. About 60% of known trait-associated loci are in linkage
disequilibrium with a cis-eQTL, over half of which were not found in previous
large-scale whole blood studies. Applying polygenic analyses to metabolic,
cardiovascular, anthropometric, autoimmune, and neurodegenerative traits, we find
that eQTLs are significantly enriched for trait associations in relevant
pathogenic tissues and explain a substantial proportion of the heritability (40
80%). For most traits, tissue-shared eQTLs underlie a greater proportion of trait
associations, although tissue-specific eQTLs have a greater contribution to some
traits, such as blood pressure. By integrating information from biological
pathways with eQTL target genes and applying a gene-based approach, we validate
previously implicated causal genes and pathways, and propose new variant and gene
associations for several complex traits, which we replicate in the UK BioBank and
BioVU.
PMID- 29955181
TI - Publisher Correction: Molecular subtypes of diffuse large B cell lymphoma are
associated with distinct pathogenic mechanisms and outcomes.
AB - In the version of this article originally published, some text above the "Tri
nucleotide sequence motifs" label in Fig. 2a appeared incorrectly. The text was
garbled and should have appeared as nucleotide codes.Additionally, the labels on
the bars in Fig. 2c were not italicized in the original publication. These are
gene symbols, and they should have been italicized.The colored labels above the
graphs in Fig. 4b were also erroneously not italicized. These labels represent
gene names and loci, and they should have been italicized.
PMID- 29955183
TI - [Analysis of our experience in the diagnosis and treatment of obturator hernia in
a third level hospital].
AB - Hernia pathology accounts for a large percentage of urgent surgical
interventions. Obturator hernia is rare, usually presenting as a picture of acute
intestinal occlusion. The aim of the study is to analyze the experience in a
third level hospital in the diagnosis and treatment of obturator hernia, as well
as to detect those signs that allow an early diagnosis. This is a prospective
observational study, which included patients operated on urgently for obturator
hernia between 2000 and 2016. For the registration of postoperative morbidity,
the Clavien-Dindo classification was used. We identified twelve patients with
intestinal obstruction secondary to obturator hernia. All of them were operated
on urgently. Urgent midline laparotomy was carried out on 59% of them,
infraumbilical laparotomy on 33%, and a posterior inguinal approach was realized
on only one patient (8%). In eight patients (67%) it was necessary to perform
intestinal resection. Repair was performed by polypropylene mesh in six patients
(50%), by plugging in two (17%) and closing with loose stitches in four patients
(33%). Four of them presented postoperative complications, recording a single
exitus secondary to perforation due to intestinal suffering. Obturator hernia is
a rare entity that develops mostly as an occlusive condition in elderly women.
The imaging technique of choice for diagnosis is computed tomography.
Establishing an early diagnosis and urgent surgical treatment is a priority to
reduce associated morbidity and mortality.
PMID- 29955184
TI - [Internal jugular venous valve as a cause of difficult central venous access].
AB - Central venous cannulation is a commonly performed procedure in the hospital
setting, while the internal jugular vein is one of the most frequently used to
perform central venous access. The presence of venous valves in the jugular veins
is a well-known fact, albeit often neglected during central venous cannulation.
However, venous valves can make this procedure difficult, increasing the chance
of developing complications. We report the case of a patient in whom the presence
of a valve in the internal jugular vein did not permit a vascular access to be
obtained through this vessel.
PMID- 29955182
TI - Author Correction: Molecular subtypes of diffuse large B cell lymphoma are
associated with distinct pathogenic mechanisms and outcomes.
AB - In the version of this article originally published, an asterisk was omitted from
Fig. 1a. The asterisk has been added to the figure. Additionally, a "NOTCH2"
label was erroneously included in Fig. 4a. The label has been removed. The errors
have been corrected in the PDF and HTML versions of this article.
PMID- 29955185
TI - The role of nCD64 in the diagnosis of neonatal sepsis in preterm newborns.
AB - BACKGROUND: Diagnosing neonatal sepsis is difficult, particularly in preterm
newborns. A promising method appears to be evaluation of cell surface markers by
flow cytometry. METHODS: This prospective study investigated 217 newborns
suspected of having early- or late-onset neonatal sepsis. In all, flow cytometry
was used to determine the proportion of CD64-positive neutrophils (nCD64). Based
on the clinical course and laboratory test results, newborns were categorized as
having proven, possible, clinical or no neonatal sepsis. Subsequently,
associations between the categories and nCD64 values were analyzed. RESULTS:
There were significant associations between nCD64 values and the development of
sepsis in newborns with both early- or late-onset sepsis. CONCLUSION:
nCD64expression is significantly elevated in preterm newborn with early and late
onset sepsis. The results show that nCD64 is a reliable marker for diagnosing
neonatal sepsis.
PMID- 29955186
TI - Comparison of two modes of long-term ECG monitoring to assess the efficacy of
catheter ablation for paroxysmal atrial fibrillation.
AB - AIMS: Optimal ECG monitoring in detecting recurrences of atrial fibrillation (AF)
or atrial tachycardia (AT) after catheter ablation has not been well established.
The purpose of this prospective study was to compare the utility of daily ECG
monitoring with episodic card recorder (ECR) vs. periodic monitoring with
episodic loop recorder (ELR) for the detection of post-blanking AF/AT recurrences
during early (Months 4-6) and late (Months 7-12) periods after catheter ablation
for paroxysmal AF. METHODS: The study included 105 consecutive patients, who
received ECR for 12 months and were instructed to send at least 2 random ECG
recordings daily with extra-recordings during symptoms. The patients were
simultaneously monitored for one week with ELR at the end of each period (Months
6 and 12). RESULTS: Thirty-one and 12 patients with AF/AT recurrence were
identified by means of ECR and ELR, respectively. In patients with complete and
valid data, ELR technology was inferior to ECR by detecting AF/AT in 5 (31%) of
16 and 5 (26%) of 19 patients with arrhythmia identified by ECR in the early and
late period, respectively. Overall, ELR had a sensitivity of 8/23 (35%) for
detecting AF/AT recurrence. There was no single patient with AF/AT recurrence on
ELR that would not be known from ECR monitoring. Only 2 patients with arrhythmia
recurrence were completely asymptomatic throughout the study period. CONCLUSION:
Daily ECG monitoring with ECR was better than periodic monitoring with ELR in
detecting AF/AT recurrences during the follow-up periods. Entirely asymptomatic
patients with AF/AT recurrences were rare.
PMID- 29955187
TI - The Value of Drug Stability Studies and Their Publication.
PMID- 29955188
TI - ?
PMID- 29955189
TI - Stability of Extemporaneously Compounded Domperidone 5 mg/mL Suspension in Oral
Mix in Plastic and Glass Bottles and Plastic Syringes.
AB - Background: Domperidone liquid for oral administration is not commercially
available in Canada, but is needed for patients who cannot swallow intact
tablets. Objective: To evaluate the stability of domperidone 5 mg/mL suspensions
prepared in Oral Mix vehicle and stored, for up to 91 days, in amber
polyvinylchloride (PVC) bottles, amber glass bottles, or amber polyethylene
terephthalate (PET) bottles at 4 degrees C or 25 degrees C or in polypropylene
oral syringes at 25 degrees C. Methods: Three separate 300-mL batches of
domperidone suspension 5 mg/mL were prepared with Oral Mix vehicle. Fifty
millilitre aliquots of the suspension were stored in 100-mL bottles (amber PVC,
amber glass, or amber PET). Half of the bottles of each type were stored at 25
degrees C and half at 4 degrees C. On study days 0, 1, 2, 4, 7, 10, 14, 21, 28,
35, 42, 49, 63, 77, and 91, domperidone concentration was determined, with a
validated reverse-phase, stability-indicating liquid chromatographic method, in
samples drawn from each type of container stored at each temperature. In
addition, 1.5-mL aliquots of a fourth 100-mL batch of suspension were stored in 3
mL oral syringes at 25 degrees C and were tested on the same study days. Results:
The concentration of domperidone in all study samples remained above 93% of
initial concentration after storage for 91 days. The percent remaining on day 91,
based on fastest degradation rate (as represented by the lower limit of the 95%
confidence interval [CI]), was at least 92.3% for suspensions stored at 4 degrees
C in PVC, glass, and PET bottles. With storage at 25 degrees C, suspensions in
PVC and glass bottles retained more than 90% of initial concentration, whereas
suspensions in PET bottles and plastic syringes retained 88.9% and 88.0% of
initial concentration, respectively. Conclusions: Because suspensions of
domperidone in PET bottles and oral syringes retained less than 90% of their
initial concentration on day 91 (based on the 95% CI), it is suggested that such
suspensions be stored at 4 degrees C or 25 degrees C in any bottle type or
syringe with an assigned beyond-use date not exceeding 75 days.
PMID- 29955191
TI - Implementation of a Pharmacist-Led Inpatient Tobacco Cessation Intervention in a
Rehabilitation Hospital: A Before-and-After Pilot Study.
AB - Background: Inpatient rehabilitation presents a unique opportunity for smoking
interventions, given the typical lengths of stay, the relevance of smoking to the
admission diagnosis of many patients, and the occurrence of nicotine withdrawal
during the hospital stay. Objective: To evaluate the feasibility of implementing
a pharmacist-led version of the Ottawa Model for Smoking Cessation (OMSC) program
at a rehabilitation hospital, using the indicators of reach, effectiveness,
adoption, and implementation. Methods: A before-and-after pilot study was
conducted. Smoking cessation data were collected from 2 cohorts of eligible
smokers identified during 4-month periods before (control) and after
(intervention) implementation of the OMSC program. Control participants received
usual care (i.e., no cessation intervention). Intervention participants received
initial in-hospital smoking cessation support (counselling and nicotine
replacement therapy), inpatient follow-up during the hospital stay, and 3 months
of postdischarge follow-up calls, with all aspects led by hospital pharmacists.
Results: Among all patients admitted to participating inpatient rehabilitation
units during the 2 study periods, smoking prevalence was 7.8% (127/1626). After
exclusions, deaths, and withdrawals, 111 patients were retained for analysis: 55
in the control group and 56 in the intervention group. The overall mean age of
participants was 64.9 (standard deviation [SD] 14.3) years, with a mean smoking
history of 35.0 (SD 24.8) pack-years. There were no significant differences
between groups in terms of baseline characteristics. Self-reported abstinence
rates (determined 3 months after discharge) were higher after compared with
before implementation of the OMSC program: for continuous abstinence, 16/56
(28.6%) versus 9/55 (16.4%), chi2 = 4.462, p = 0.035; for 7-day point prevalence
abstinence, 21/56 (37.5%) versus 10/55 (18.2%), chi2 = 6.807, p = 0.009.
Conclusions: Implementation of the OMSC program at a large rehabilitation
hospital was feasible and led to an increase in 3-month smoking abstinence. This
study provides preliminary evidence to support inclusion of smoking interventions
as part of inpatient rehabilitation care.
PMID- 29955190
TI - Ferric Gluconate Complex in Elderly Hospital Inpatients without Terminal Kidney
Failure.
AB - Background: Anemia is a common health issue for elderly patients. For patients
with iron deficiency who cannot tolerate iron supplementation by the oral route,
the parenteral route may be used. Options for parenteral iron supplementation
include ferric gluconate complex (FGC). Objectives: To evaluate the safety of FGC
in elderly patients without terminal kidney failure and to assess its efficacy in
treating iron-deficiency anemia. Methods: An observational chart review was
conducted at a tertiary care university health centre. Patients included in the
study were 65 years of age or older, had received at least 1 dose of FGC between
January 1, 2014, and December 31, 2015, and had a hemoglobin count of less than
130 g/L (men) or less than 120 g/L (women) at baseline. For each patient, the
observation period began when the first dose of FGC was administered and ended 60
days after the last dose. The main safety outcome (occurrence of any adverse
reaction) was evaluated for every patient, with the efficacy analysis being
limited to patients with a diagnosis of iron-deficiency anemia. Results: A total
of 144 patients were included in the study, of whom 76 had iron-deficiency
anemia. No serious, life-threatening adverse reactions were reported. The most
commonly reported adverse reactions were nausea and vomiting. The mean increase
in hemoglobin count was 13.5 g/L, a statistically significant change from
baseline. Conclusions: These results show that FGC is safe for use in elderly
patients, with very few mild adverse reactions. Use of FGC led to increased
hemoglobin count within 60 days. Of the 3 options for parenteral iron
supplementation available in Canada, iron sucrose has not been studied in elderly
patients, and iron dextran has a higher incidence of anaphylaxis, whereas FGC
appears to be a safe alternative for patients with intolerance to oral iron.
PMID- 29955192
TI - ?
AB - Background: The scientific literature on knowledge translation (KT) is vast and
complex, and most publications concerning health care interventions involve
physicians and nurses. To the authors' knowledge, there have been no literature
reviews on KT and its impact on pharmacy practice. Objective: To determine the
profile of interventions relating to KT in pharmacy practice. Data Sources: The
term "pharmacist" was used to search the web platform Knowledge Translation+
(KT+) to identify pertinent articles published between January 2010 and December
2016. Study Selection and Data Extraction: The main variables analyzed to
determine the profile of KT interventions in pharmacy practice were the study's
research protocol, the geographic location of the intervention, pharmacist roles,
the types of knowledge transferred, and impacts of the interventions. The nature
of pharmacy interventions was coded according to the classification on the Impact
Pharmacie website. Data Synthesis: A total of 114 articles were selected:
systematic reviews (n = 25, 22%), randomized controlled trials (n = 45, 40%),
retrospective studies (n = 21, 18%), prospective studies (n = 13, 11%), and pre
post intervention studies (n = 10, 9%). Most of the studies (74%) were conducted
in a health care institution. The majority of interventions targeted
pharmaceutical care steps, therapeutic educational sessions, and patient
education. There was a lack of methodological rigour during the development of
interventions and in their description. Conclusion: Pharmacists are key
generators of knowledge, and their interventions related to KT are directed
toward patients or other health care professionals. These interventions have
mainly addressed the pharmaceutical care process and interdisciplinary work. The
implementation of initial and continuing education, the management of
information, and the designation of a pharmacist responsible for KT in each
pharmacy department might promote the development of such KT. This concept might
in turn support the design of a coherent pharmacy practice model.
PMID- 29955193
TI - Interaction between Monoamine Oxidase B Inhibitors and Selective Serotonin
Reuptake Inhibitors.
AB - Background: Monoamine oxidase B (MAO-B) inhibitors are used to treat the motor
symptoms of Parkinson disease. Depression is commonly associated with Parkinson
disease, and selective serotonin reuptake inhibitors (SSRIs) are often used for
its management. Tertiary sources warn that the combination of MAO-B inhibitors
and SSRIs can result in increased serotonergic effects, leading to serotonin
syndrome. Objective: To explore the mechanism, clinical significance, and
management of this potential drug interaction through a review of the supporting
evidence. Data Sources: PubMed, MEDLINE (1946 forward), Embase (1947 forward),
PsycINFO (1806 forward), and International Pharmaceutical Abstracts (1970
forward) were searched on February 4, 2017. Study Selection and Data Extraction:
Studies and case reports describing aspects of the potential interaction between
MAO-B inhibitors and SSRIs in patients with Parkinson disease and published in
English were identified by both title and abstract. Data Synthesis: The search
identified 8 studies evaluating the potential interaction between SSRIs and the
MAO-B inhibitors selegiline and rasagiline. The largest, a retrospective cohort
study of 1504 patients with Parkinson disease, found no cases of serotonin
syndrome with coadministration of rasagiline and an SSRI. A survey of 63
investigators in the Parkinson Study Group identified 11 potential cases of
serotonin syndrome among 4568 patients treated with the combination of selegiline
and antidepressants (including SSRIs). In addition, 17 case reports describing
the onset of serotonin syndrome with coadministration of an SSRI and either
selegiline or rasagiline were identified. Following discontinuation or dose
reduction of one or both of the agents, the symptoms of serotonin syndrome
gradually resolved in most cases, with none being fatal. Conclusions: According
to the literature, serotonin syndrome occurs rarely, and the combination of SSRI
and MAO-B inhibitor is well tolerated. Therefore, SSRIs and MAO-B inhibitors can
be coadministered, provided that their recommended doses are not exceeded and the
SSRI dose is kept at the lower end of the therapeutic range. Among the SSRIs,
citalopram and sertraline may be preferred.
PMID- 29955194
TI - Brevundimonas vesicularis Causing Bilateral Pneumosepsis in an Immunocompetent
Adult: A Case Report and Literature Review.
PMID- 29955195
TI - Should Medical Cannabis Administered by Inhalation Be Allowed for Hospitalized
Patients?
PMID- 29955196
TI - Pharmacists' Roles in Critical Care: Environmental Scan of Current Practices in
Canadian Intensive Care Units.
PMID- 29955197
TI - Cotrimoxazole-Induced Tremor.
PMID- 29955198
TI - ?
PMID- 29955199
TI - The Canadian Opioid Crisis: CSHP's Commitment.
PMID- 29955201
TI - Free alpha-Oxiranyl Amino Acids.
PMID- 29955200
TI - Evolutionary Adaptation and Amyloid Formation: Does the Reduced Amyloidogenicity
and Cytotoxicity of Ursine Amylin Contribute to the Metabolic Adaption of Bears
and Polar Bears?
AB - Much of our knowledge of diabetes is derived from studies of rodent models. An
alternative approach explores evolutionary solutions to physiological stress by
studying organisms that face challenging metabolic environments. Polar bears eat
an enormously lipid-rich diet without deleterious metabolic consequences. In
contrast, transgenic rodents expressing the human neuropancreatic polypeptide
hormone amylin develop hyperglycemia and extensive pancreatic islet amyloid when
fed a high fat diet. The process of islet amyloid formation by human amylin
contributes to beta-cell dysfunction and loss of beta-cell mass in type-2
diabetes. We show that ursine amylin is considerably less amyloidogenic and less
toxic to beta-cells than human amylin, consistent with the hypothesis that part
of the adaptation of bears to metabolic challenges might include protection from
islet amyloidosis-induced beta-cell toxicity. Ursine and human amylin differ at
four locations: H18R, S20G, F23L, and S29P. These are interesting from a
biophysical perspective since the S20G mutation accelerates amyloid formation but
the H18R slows it. An H18RS20G double mutant of human amylin behaves similarly to
the H18R mutant, indicating that the substitution at position 18 dominates the
S20G replacement. These data suggest one possible mechanism underpinning the
protection of bears against metabolic challenges and provide insight into the
design of soluble analogs of human amylin.
PMID- 29955202
TI - Addiction medicine and addiction psychiatry in America: Commonalities in the
medical treatment of addiction.
AB - Two competing medical disciplines treat addiction in the United States: addiction
medicine and addiction psychiatry. Addiction medicine seeks recognition from the
American Board of Medical Specialties whereas addiction psychiatry holds this
high-level medical status, a mission that suggests a substantive distinction
between addiction medicine physicians and addiction psychiatrists that does not
exist. As this article shows, leading addiction medicine physicians and addiction
psychiatrists agree on the definition of addiction and that drug treatment is an
"art" which requires a multimethod approach. Despite this extensive accord,
addiction medicine physicians and addiction psychiatrists draw sharp distinctions
between addiction medicine and addiction psychiatry to serve historical,
economic, and professional interests, revealing the importance to both
disciplines of recognition from the American Board of Medical Specialties and
thus jurisdiction over the medical treatment of addiction.
PMID- 29955204
TI - Indirect photopatterning of functionalized organic monolayers via copper
catalyzed "click chemistry".
AB - Solution-based lithographic surface modification of an organic monolayer on a
solid substrate is attained based on selective area photo-reduction of copper
(II) to copper (I) to catalyze the azide-alkyne dipolar cycloaddition "click"
reaction. X-ray photoelectron spectroscopy is used to confirm patterning, and
spectroscopic results are analyzed and supplemented with computational models to
confirm the surface chemistry. It is determined that this surface modification
approach requires irradiation of the solid substrate with all necessary
components present in solution. This method requires only minutes of irradiation
to result in spatial and temporal control of the covalent surface
functionalization of a monolayer and offers the potential for wavelength
tunability that may be desirable in many applications utilizing organic
monolayers.
PMID- 29955203
TI - Large-scale generation and analysis of filamentous fungal DNA barcodes boosts
coverage for kingdom fungi and reveals thresholds for fungal species and higher
taxon delimitation.
AB - Species identification lies at the heart of biodiversity studies that has in
recent years favoured DNA-based approaches. Microbial Biological Resource Centres
are a rich source for diverse and high-quality reference materials in
microbiology, and yet the strains preserved in these biobanks have been exploited
only on a limited scale to generate DNA barcodes. As part of a project funded in
the Netherlands to barcode specimens of major national biobanks, sequences of two
nuclear ribosomal genetic markers, the Internal Transcribed Spaces and 5.8S gene
(ITS) and the D1/D2 domain of the 26S Large Subunit (LSU), were generated as DNA
barcode data for ca. 100 000 fungal strains originally assigned to ca. 17 000
species in the CBS fungal biobank maintained at the Westerdijk Fungal
Biodiversity Institute, Utrecht. Using more than 24 000 DNA barcode sequences of
12 000 ex-type and manually validated filamentous fungal strains of 7 300
accepted species, the optimal identity thresholds to discriminate filamentous
fungal species were predicted as 99.6 % for ITS and 99.8 % for LSU. We showed
that 17 % and 18 % of the species could not be discriminated by the ITS and LSU
genetic markers, respectively. Among them, ~8 % were indistinguishable using both
genetic markers. ITS has been shown to outperform LSU in filamentous fungal
species discrimination with a probability of correct identification of 82 % vs.
77.6 %, and a clustering quality value of 84 % vs. 77.7 %. At higher taxonomic
classifications, LSU has been shown to have a better discriminatory power than
ITS. With a clustering quality value of 80 %, LSU outperformed ITS in identifying
filamentous fungi at the ordinal level. At the generic level, the clustering
quality values produced by both genetic markers were low, indicating the
necessity for taxonomic revisions at genus level and, likely, for applying more
conserved genetic markers or even whole genomes. The taxonomic thresholds
predicted for filamentous fungal identification at the genus, family, order and
class levels were 94.3 %, 88.5 %, 81.2 % and 80.9 % based on ITS barcodes, and
98.2 %, 96.2 %, 94.7 % and 92.7 % based on LSU barcodes. The DNA barcodes used in
this study have been deposited to GenBank and will also be publicly available at
the Westerdijk Institute's website as reference sequences for fungal
identification, marking an unprecedented data release event in global fungal
barcoding efforts to date.
PMID- 29955205
TI - Childcare Type and Quality among Subsidy Recipients with and without Special
Needs.
AB - Low-income children, particularly those with special needs, may have limited
access to high quality early care experiences. Child care subsidies are intended
to increase families' access to quality care, but little is known about subsidy
use by children with special needs. Using a nationally representative sample of
4,000 young children who participated in the Early Childhood Longitudinal Study -
Birth Cohort, we examined the types and quality of childcare received by children
with and without special needs who came from subsidy eligible families. We also
investigated the extent to which subsidy use and child and family
sociodemographic characteristics predicted care type and quality among young
children with special needs who used childcare subsidies at nine months, two
years, and four years. Findings indicated that subsidies increased the use of non
parental care, mainly center-based care, as well as home-based care to a lesser
extent among children with special needs relative to peers without special needs
and relative to peers with special needs who did not use subsidies. However, use
of subsidy did not consistently result in families with children with special
needs accessing higher quality care. Sociodemographic characteristics of
children, families and their context were differentially predictive of type and
quality care. We discuss implications for practice and policy to foster quality
early care and education of young children with special needs who are receiving
subsidies.
PMID- 29955206
TI - The Apolipoprotein E Mimetic Peptide AEM-2 Attenuates Mitochondrial Injury And
Apoptosis In Human THP-1 Macrophages.
AB - Cardiovascular disease, specifically atherosclerosis, is exacerbated by
hypercholesterolemia. Current therapies that target lipid lowering, however, are
not effective in all patients. Apolipoprotein E (apoE) plays an important role in
mediating the clearance of plasma cholesterol and also exerts numerous
cytoprotective responses. Our laboratory has synthesized novel therapeutics that
mimic the ability of apoE to decrease plasma cholesterol. The apoE mimetic
peptide AEM-2 is a dual domain peptide composed of an amphipathic helical region
that binds phospholipids and a positively charged region that mediates the
hepatic clearance of lipoproteins. Administration of AEM-2 to apoE null mice
reduced plasma cholesterol concentration by 80% one hour post-administration.
Since apoE is also known to exert anti-inflammatory effects that are independent
of its ability to lower cholesterol, we tested effects of AEM-2 on
lipopolysaccharide-induced responses in human THP-1 macrophages. Pre-treatment of
THP-1 cells with AEM-2 significantly reduced the LPS-induced secretion of IL-6
and TNFalpha. Since LPS administration is associated with an increase in
mitochondrial injury, we monitored effects of AEM-2 on mitochondrial function.
AEM-2 significantly reduced mitochondrial superoxide formation, prevented the LPS
induced decrease in mitochondrial membrane potential and attenuated the release
of cytochrome c. AEM-2 also inhibited the activities of initiator caspases 8 and
9 and effector caspase 3. The attenuation of apoptosis in AEM-2 treated cells was
associated with an increase in cellular autophagy. These data suggest that AEM-2
attenuates cellular injury in LPS-treated THP-1 macrophages and facilitates the
removal of cellular debris and damaged organelles via induction of autophagy.
PMID- 29955208
TI - Regional differences in dopamine release in the R6/2 mouse caudate putamen.
AB - Huntington's disease (HD) is a fatal neurodegenerative disorder that is
characterized by degeneration of the striatum. Here, fast-scan cyclic voltammetry
at carbon-fiber microelectrodes was used to uncover regional differences in
dopamine (DA) release in the caudate putamen of R6/2 and wild-type control mice.
We found a decreasing ventral-to-dorsal gradient in DA release, evoked by a
single electrical stimulus pulse, in aged R6/2 mice. Moreover, under more intense
stimulation conditions (120 pulses), DA release was significantly attenuated in
the dorsal, but not in the ventral caudate. Autoradiography measurements using
[3H]WIN 35,428 revealed that the overall density of DA transporter (DAT) protein
molecules was significantly less in R6/2 mice compared to WT control mice;
however, quadrants of the caudate putamen were not differentially altered in the
R6/2 mice. These data collectively suggest that DA release in the dorsal caudate
region is more vulnerable with age progression compared to the ventral region.
PMID- 29955209
TI - Taxonomy of the ant genus Carebara Westwood (Formicidae, Myrmicinae) in the
Malagasy Region.
AB - The genus Carebara is revised for the Malagasy region, and based on the
examination of over 10,000 specimens, twenty-three species are recognized. Twenty
one of these are described as new (C. barasp. n., C. berivelosp. n., C. betsisp.
n., C. creoleisp. n., C. demetersp. n., C. dotasp. n., C. haintenysp. n., C.
hiragasysp. n., C. jajobysp. n., C. kabosysp. n., C. lovasp. n., C. mahafalysp.
n., C. malagasysp. n., C. omasisp. n., C. placidasp. n., C. raberisp. n., C.
salegisp. n., C. sampisp. n., C. tanasp. n., C. tananasp. n., C. vazimbasp. n.),
and two are redescribed, C. grandidieri Forel (= C. voeltzkowi Forel n. syn.) and
C. nosindambo Forel. A lectotype is designated for C. nosindambo. C. creoleisp.
n. is known only from Mauritius and Seychelles, C. grandidieri Forel is
distributed in Comoros, Madagascar and Mayotte, and the other twenty-one species
are endemic to Madagascar. Most of the Carebara species recorded in this work are
endemic to a specific habitat (ecoregion), but some of them (C. barasp. n., C.
grandidieri Forel, C. jajobysp. n., C. kabosysp. n., and C. nosindambo Forel) are
widespread within Madagascar across all major habitats. The worker caste of
Carebara can be differentiated from other genera in the Myrmicinae subfamily by
the presence of the following combination of characters: antennae of eight to
eleven segments, with a two-segmented club; anterior clypeal margin without
central isolated seta (rarely present in some species or specimens), and usually
with four distinct setae; mandibles with four to seven teeth (except in one
species from Ghana - C. crigensis with three teeth); and palp formula 2,2 or 1,2.
We report that almost all Carebara species found in the Malagasy region have
intermediates (distinct forms) in the major worker subcaste, with the largest
major workers showing remnants of queen flight sclerites and ocelli. The
widespread presence of intermediates in the major worker subcaste expands the
morphological boundaries of Carebara. We present an overview of the natural
history of Carebara in the Malagasy region, an illustrated key for the
identification of the known Malagasy species of Carebara, as well as high
resolution images and distribution maps. Unique identifiers are used for all
specimens studied, including type material, and the raw data that forms the basis
of this study are available on www.antweb.org (open access).
PMID- 29955207
TI - Nonlinear Optical Methods for Characterization of Molecular Structure and Surface
Chemistry.
AB - The principles, strengths and limitations of several nonlinear optical (NLO)
methods for characterizing biological systems are reviewed. NLO methods encompass
a wide range of approaches that can be used for real-time, in-situ
characterization of biological systems, typically in a label-free mode.
Multiphoton excitation fluorescence (MPEF) is widely used for high-quality
imaging based on electronic transitions, but lacks interface specificity. Second
harmonic generation (SHG) is a parametric process that has all the virtues of the
two-photon version of MPEF, yielding a signal at twice the frequency of the
excitation light, which provides interface specificity. Both SHG and MPEF can
provide images with high structural contrast, but they typically lack molecular
or chemical specificity. Other NLO methods such as coherent anti-Stokes Raman
scattering (CARS) and stimulated Raman scattering (SRS) can provide high
sensitivity imaging with chemical information since Raman active vibrations are
probed. However, CARS and SRS lack interface and surface specificity. A NLO
method that provides both interface/surface specificity as well as molecular
specificity is vibrational sum frequency generation (SFG) spectroscopy. Vibration
modes that are both Raman and IR active are probed in the SFG process, providing
the molecular specificity. SFG, like SHG, is a parametric process, which provides
the interface and surface specificity. SFG is typically done in the reflection
mode from planar samples. This has yielded rich and detailed information about
the molecular structure of biomaterial interfaces and biomolecules interacting
with their surfaces. However, 2-D systems have limitations for understanding the
interactions of biomolecules and interfaces in the 3-D biological environment.
The recent advances made in instrumentation and analysis methods for sum
frequency scattering (SFS) now present the opportunity for SFS to be used to
directly study biological solutions. By detecting the scattering at angles away
from the phase-matched direction even centrosymmetric structures that are
isotropic (e.g., spherical nanoparticles functionalized with self-assembled
monolayers or biomolecules) can be probed. Often a combination of multiple NLO
methods or a combination of a NLO method with other spectroscopic methods is
required to obtain a full understanding of the molecular structure and surface
chemistry of biomaterials and the biomolecules that interact with them. Using the
right combination methods provides a powerful approach for characterizing
biological materials.
PMID- 29955210
TI - Two new species of genus Oecleopsis Emeljanov from China, with descriptions of
female genitalia of five species (Hemiptera, Fulgoromorpha, Cixiidae).
AB - Two new species of genus Oecleopsis Emeljanov, 1971, O. laminatus Zhi & Chen, sp.
n. and O. productus Zhi & Chen, sp. n., and a new record, O. yoshikawai
(Ishihara, 1961), are described and illustrated from China. Female genitalia of
five species within this genus are compared morphologically: O. laminatus Zhi &
Chen, sp. n., O. mori (Matsumura, 1914), O. productus Zhi & Chen, sp. n., O.
sinicus (Jacobi, 1944) and O. yoshikawai (Ishihara, 1961). A key to five Chinese
species based on female genitalia, and a key to all known species of Oecleopsis
based on male genitalia, are provided.
PMID- 29955211
TI - North American Xyleborini north of Mexico: a review and key to genera and species
(Coleoptera, Curculionidae, Scolytinae).
AB - Bark and ambrosia beetles (Scolytinae) are the most successful group of invasive
wood borers worldwide, and the most invasive among them are species in the tribe
Xyleborini. This haplodiploid, highly inbred, fungus-farming group is represented
by 30 non-native species in North America, of which at least five are serious
pests. The few identification resources for Xyleborini that exist are becoming
outdated due to new species arrivals and nomenclatural changes. Here we present a
new comprehensive key to Xyleborini currently known from the continental United
States. Compared to the previous key, the following species have been added to
the North American fauna: Ambrosiodmus minor (Stebbing), Ambrosiophilus nodulosus
(Eggers), Anisandrus maiche Kurentsov, Coptoborus pseudotenuis (Schedl),
Cyclorhipidion fukiense (Eggers), Dryocoetoides reticulatus Atkinson, Dryoxylon
onoharaense (Murayama), Euwallacea interjectus (Blandford), Xyleborinus andrewesi
(Blandford), Xyleborinus artestriatus (Eichhoff), Xyleborinus octiesdentatus
(Murayama), Xyleborus bispinatus Eichhoff, Xyleborus seriatus Blandford,
Xyleborus spinulosus Blandford, and Xylosandrus amputatus (Blandford).
PMID- 29955212
TI - Evidence of hidden diversity and taxonomic conflicts in five stream fishes from
the Eastern Zimbabwe Highlands freshwater ecoregion.
AB - Stream fishes of the Eastern Afromontane region are among the least studied
vertebrates in this region, despite the potential for harbouring cryptic
diversity. The present study examined mitochondrial cytochrome oxidase subunit I
(COI) sequence divergence in 153 specimens of stream fishes belonging to four
genera and three families, [(Amphilius and Zaireichthys (Amphiliidae);
Chiloglanis (Mochokidae); and Hippopotamyrus (Mormyridae)], in the Eastern
Zimbabwe Highlands (EZH) freshwater ecoregion to explore the extent to which the
current taxonomy conceals the ichthyofaunal diversity in the region. The General
Mixed Yule Coalescent (GMYC) species delineation method identified 14 clusters
within five currently recognised 'species' from the EZH ecoregion. Only one of
these clusters represents a named species, while 13 of them represent candidate
or undescribed species. Our results revealed that effective conservation of this
region's unique biota is limited by the incomplete knowledge of taxonomic
diversity and inaccurate mapping of species distribution ranges.
PMID- 29955213
TI - Macrocheles kekensis sp. n., a new macrochelid mite associated with a centoniin
beetle from Hungary (Acari, Mesostigmata).
AB - A new species, Macrocheles kekensissp. n., is described based from three
specimens associated with a cetoniin beetle (Hoplia hungarica Burmeister, 1844).
The new species differs from the other known European macrochelid species in
having 29 pairs of dorsal setae, j1 and z1 short and robust, other dorsal setae
long and pilose, and the absence of apodemes between the genital and ventrianal
shields. This is the 34th Hungarian macrochelid species.
PMID- 29955214
TI - Barsine podbolotskayae sp. n. from Flores Island, Lesser Sunda Archipelago,
Indonesia (Lepidoptera, Erebidae, Arctiinae).
AB - Herein Barsine podbolotskayaesp. n. (Lepidoptera: Erebidae: Arctiinae) is
described from Flores Island, Lesser Sunda Archipelago, Indonesia. This local
endemic species externally resembles Barsine exclusa Butler, 1877 from Sundaland
and the Andaman Islands but differs by marking patterns and male genitalia
structure.
PMID- 29955215
TI - Three new genera of acidocerine water scavenger beetles from tropical South
America (Coleoptera, Hydrophilidae, Acidocerinae).
AB - Recent collecting efforts in the Neotropics have led to the discovery of numerous
new species and lineages of aquatic beetles. Here, three new genera are described
to accommodate fifteen new species of water scavenger beetles of the subfamily
Acidocerinae from northern South America: Crucisternumgen. n. for C. escalerasp.
n. (Venezuela), C. ouboterisp. n. (Guyana, French Guiana, Suriname, Venezuela),
C. queneyisp. n. (French Guiana), C. sinuatussp. n. (Brazil), C. toboganensissp.
n. (Venezuela), C. vanessaesp. n. (Suriname), and C. xingusp. n. (Brazil);
Katasophistesgen. n. for K. charynaesp. n. (Peru), K. cuzcosp. n. (Peru), K.
meridasp. n. (Venezuela) and K. superficialissp. n. (Ecuador); and Nanosaphesgen.
n. for N. castaneussp. n. (Brazil), N. hesperussp. n. (Suriname), N. punctatussp.
n. (Guyana), and N. tricolorsp. n. (Guyana, Suriname). It was also found that the
monotypic Neotropical endemic genus Dieroxenus Spangler, 1979, syn. n. is
congeneric with Chasmogenus Sharp, 1882 resulting in the single new combination
Chasmogenus cremnobates (Spangler, 1979), comb. n.. Katasophistes meridasp. n. is
known exclusively from seepage habitats, while the remaining taxa described
herein are primarily associated with the margins of densely forested streams.
Diagnoses, illustrations, distribution maps, and habitat summaries are provided
for all new genera and species. A key to the genera of Acidocerinae of the New
World is provided.
PMID- 29955216
TI - Georeferenced sighting and specimen occurrence data of the extinct Carolina
Parakeet (Conuropsis carolinensis) from 1564 - 1944.
AB - Background: Despite much present-day attention on recently extinct North American
birds species, little contemporary research has focused on the Carolina parakeet
(Conuropsis carolinesis). While the last captive Carolina parakeet died 100 years
ago this year, the Carolina parakeet was officially declared extinct in 1920, but
they likely persisted in small, isolated populations until at least the 1930s,
and perhaps longer. How this once wide-ranging and plentiful species went extinct
remains a mystery. Here, we present a georeferenced dataset of Carolina parakeet
sightings spanning nearly 400 years by combining both written observations and
specimen data. New information: Because we include both observations and specimen
data, the Carolina parakeet occurrence dataset presented here is the most
comprehensive and rigorous datsetset on this species available. The dataset
includes 861 sightings from 1564 to 1944. Each datapoint includes geographic
coordinates, a measurement of uncertainty, detailed information about each
sighting, and an assessment of the sighting's validity. Given that this species
is so poorly understood, we make these data freely available to facilitate more
research on this colorful and charismatic species.
PMID- 29955217
TI - Importance of Nutrients and Nutrient Metabolism on Human Health.
AB - Nutrition transition, which includes a change from consumption of traditional to
modern diets that feature high-energy density and low nutrient diversity, is
associated with acquired metabolic syndromes. The human diet is comprised of
diverse components which include both nutrients, supplying the raw materials that
drive multiple metabolic processes in every cell of the body, and non-nutrients.
These components and their metabolites can also regulate gene expression and
cellular function via a variety of mechanisms. Some of these components are
beneficial while others have toxic effects. Studies have found that persistent
disturbance of nutrient metabolism and/or energy homeostasis, caused by either
nutrient deficiency or excess, induces cellular stress leading to metabolic
dysregulation and tissue damage, and eventually to development of acquired
metabolic syndromes. It is now evident that metabolism is influenced by extrinsic
factors (e.g., food, xenobiotics, environment), intrinsic factors (e.g., sex,
age, gene variations) as well as host/microbiota interaction, that together
modify the risk for developing various acquired metabolic diseases. It is also
becoming apparent that intake of diets with low-energy density but high in
nutrient diversity may be the key to promoting and maintaining optimal health.
PMID- 29955218
TI - Algal Bloom Expansion Increases Cyanotoxin Risk in Food.
AB - As advances in global transportation infrastructure make it possible for out of
season foods to be available year-round, the need for assessing the risks
associated with the food production and expanded distribution are even more
important. Risks for foodborne illness are associated with contamination by
bacteria, viruses, mold, parasites, natural and synthetic toxins, chemical
residues, and conditions that lead to contamination. An increase in the
popularity of natural alternatives to pharmaceuticals, herbal remedies and the
desire for consuming "super foods" is leading to a change in the dietary patterns
of consumers. Similarly, dietary trends are plentiful, with more consumers
adopting changes with little medical guidance to dietary plans that are supported
by inadequate scientific data. In particular, U.S. consumers are acquiring novel
foods that may not be adequately checked for the presence of marine toxins and
heat stable toxins in dry or minimally processed foods. Some dry foods cultivated
in or processed in regions that may utilize hypoxic agricultural waters high in
cyanobacterial or algal contamination. These may perpetuate increased risks for
chronic liver, kidney, and neurodegenerative disorders due to intoxication from
preventable foodborne agents. Global climate change, which has the effect of
potentially expanding the toxic waters into higher latitudes, forecasts an
increase in the risk of food contamination with toxins.
PMID- 29955219
TI - More of the Gut in the Lung: How Two Microbiomes Meet in ARDS.
AB - In critically ill patients, lung and gut microbiomes undergo profound changes.
Lung microbiome might become enriched with gut-associated microbes as recently
demonstrated in sepsis and acute respiratory distress syndrome (ARDS). It has
been proposed that in these conditions, bacteria from the gut might enter the
lungs via translocation, a process facilitated by increased gut and alveolo
capillary permeability. In patients requiring mechanical ventilation after severe
trauma, lung microbiome enrichment with gut-associated microbes was found to
correlate with the development of ARDS. The lungs in ARDS are increasingly
susceptible to opportunistic infections which can further perpetuate alveolar
inflammation and injury. Undoubtedly, more research on the gut-lung crosstalk in
critically ill patients is needed to identify causal relationships between the
altered microbiome, infections, inflammation, and acute lung injury. With further
insights, this area of investigation could lead to the development of novel,
microbiome-targeted, and immunomodulation strategies with the potential to
improve outcomes of critically ill patients with sepsis, trauma, and ARDS.
PMID- 29955221
TI - History and Perspectives on Nutrition and Hydration at the End of Life.
AB - The question of whether to provide artificial nutrition and hydration (ANH) to a
patient with terminal illness or at end of life has been debated over many years.
Due to the nature of the question and the setting in which it presents,
prospective trials are not feasible, and the health care professional is left to
work with the patient and family to make decisions. This perspectives piece
addresses the issue in a format designed to inform the reader as to the pertinent
considerations around ANH. We briefly review significant historic, religious,
ethical, and legal contributions to this discussion and physiologic
underpinnings. We address the beliefs of patient, family, and health care
providers surrounding this issue. Our goal is to provide a review of the
considerations for health care providers as they address this issue with patients
and families in the course of compassionate care.
PMID- 29955220
TI - Impact of Prebiotics on Poultry Production and Food Safety.
AB - With the phasing out of routine use of antibiotics in animal agriculture,
interest has grown for the need to develop feed supplements that augment
commercial poultry performance and provide food safety benefits. From a food
safety perspective, alternative feed supplements can be broadly categorized as
either agents which reduce or eliminate already colonized foodborne pathogens or
prevent colonization of incoming pathogens. Prebiotics are considered
preventative agents since they select for gastrointestinal microbiota which not
only benefits the host but can serve as a barrier to pathogen colonization. In
poultry, prebiotics can elicit both indirect effects on the bird by shifting the
composition and fermentation patterns of the gastrointestinal microbiota or
directly by influencing host systems such as immune responses. Generation of
short chain fatty acids is believed to be a primary inhibitory mechanism against
pathogens when prebiotics are fermented by gastrointestinal bacteria, but other
mechanisms such as interference with attachment can occur as well. While most of
the impact of the prebiotic is believed to occur in the lower parts of the bird
gastrointestinal tract, particularly the ceca, it is possible that some microbial
hydrolysis could occur in upper sections such as the crop. Development of next
generation sequencing has increased the resolution of identifying
gastrointestinal organisms that are involved in metabolism of prebiotics either
directly or indirectly. Novel sources of non-digestible oligosaccharides such as
cereal grain brans are being explored for potential use in poultry to limit
Salmonella establishment. This review will cover the current applications and
prospects for use of prebiotics in poultry to improve performance and limit
pathogens in the gastrointestinal tract.
PMID- 29955222
TI - Ancient Thali Diet: Gut Microbiota, Immunity, and Health.
AB - Diet provides macronutrients (carbohydrates, proteins, and fats), micronutrients
(vitamins and minerals), and phytochemicals (non-nutrient bioactive compounds).
Emerging evidence suggests that above dietary components can directly impact the
composition and metabolic activity of the mammalian gut microbiota and in turn,
affect both physical and mental health. There is a growing recognition that rise
in chronic disease burden in Western countries may due to progressive loss of
beneficial bacteria and microbial diversity. This perspective explores the
possibility of using Indian thali, an ancient approach to diet that provides both
fiber and different phytochemicals by incorporating a variety of plant foods in
different colors. This variety helps to restore diversity in the gut bacteria and
may potentially prevent or reverse chronic disease, such as colon cancer or type
2 diabetes.
PMID- 29955223
TI - Sugar-Sweetened Beverage Taxes: Industry Response and Tactics.
AB - The consumption of sugary beverages (SBs) has increasingly grown in many
countries and is a significant contributor to the rise in obesity and non
communicable diseases (NCDs). In response, public health officials in multiple
countries have pushed for implementing a tax on SBs in order to reduce their
consumption. Today, many individuals, especially those of lower socioeconomic
status, live in environments in which unhealthy foods and drinks are more
accessible than healthier ones. The beverage industry has greatly contributed to
the formation of these "obesogenic" environments through their extensive
advertising activities and effective marketing strategies. With rising public
awareness of sugar's link to obesity, the industry has heavily invested in
campaigns that seek to shift the blame away from their products and has
aggressively opposed legislative efforts to pass an SB tax. This perspective will
focus on explaining the rationale and necessity of an SB tax by highlighting the
tactics the beverage industry has employed that have contributed to the formation
and maintenance of the present unhealthy food environment.
PMID- 29955224
TI - Food Sustainability in the Context of Human Behavior.
AB - The long-term goal of food sustainability is to produce enough food to maintain
the human population. The intrinsic factors to guarantee a sustainable food
system are a fertile land, water, fertilizers, a stable climate, and energy.
However, as the world population grows, the volume of food needed in the future
will not depend just on these intrinsic factors, but on human choices. This paper
analyzes some of the human actions that may affect the sustainable future of the
food supply chain, including diet, obesity, food miles, food waste, and
genetically modified organisms.
PMID- 29955225
TI - A New Holistic Approach to Diabetes Research: Measuring Metabolism at the
Cellular Level: An Interview with Richard Kibbey, MD, PhD.
PMID- 29955226
TI - A New Knowledge Characteristics Weighting Method Based on Rough Set and Knowledge
Granulation.
AB - The knowledge characteristics weighting plays an extremely important role in
effectively and accurately classifying knowledge. Most of the existing
characteristics weighting methods always rely heavily on the experts' a priori
knowledge, while rough set weighting method does not rely on experts' a priori
knowledge and can meet the need of objectivity. However, the current rough set
weighting methods could not obtain a balanced redundant characteristic set. Too
much redundancy might cause inaccuracy, and less redundancy might cause
ineffectiveness. In this paper, a new method based on rough set and knowledge
granulation theories is proposed to ascertain the characteristics weight.
Experimental results on several UCI data sets demonstrate that the weighting
method can effectively avoid subjective arbitrariness and avoid taking the
nonredundant characteristics as redundant characteristics.
PMID- 29955227
TI - A Composite Model of Wound Segmentation Based on Traditional Methods and Deep
Neural Networks.
AB - Wound segmentation plays an important supporting role in the wound observation
and wound healing. Current methods of image segmentation include those based on
traditional process of image and those based on deep neural networks. The
traditional methods use the artificial image features to complete the task
without large amounts of labeled data. Meanwhile, the methods based on deep
neural networks can extract the image features effectively without the artificial
design, but lots of training data are required. Combined with the advantages of
them, this paper presents a composite model of wound segmentation. The model uses
the skin with wound detection algorithm we designed in the paper to highlight
image features. Then, the preprocessed images are segmented by deep neural
networks. And semantic corrections are applied to the segmentation results at
last. The model shows a good performance in our experiment.
PMID- 29955229
TI - Isocratic Resolution of Fluoroquinolone-Based Antibiotics on the Phenylethyl
Bonded Phase under Nonaqueous Elution: A Consideration of the Separation
Mechanism.
AB - This paper reports the isocratic resolution of 10 fluoroquinolone-based
antibiotics and their precursors on the phenylethyl-bonded phase under the
elution of the nonaqueous mobile phase composed of acetonitrile, methanol, acetic
acid, and triethylamine. Most of the analytes were baseline resolved within 10
minutes. The interaction simulation and Fourier-transform infrared spectroscopy
(FTIR) data indicated that the carbonyl-containing group, a secondary or tertiary
amine of an analyte, was heavily involved in the retention, resulting in
retention with residual silanol groups on the stationary phase. In some cases,
the elution reversal or resolution enhancement of analytes was observed when the
volume of acidic or basic additive in the mobile phase was dominant. However, the
pi-pi complexation interaction between the fluorine-attached phenyl group of the
analyte and the phenylethyl moiety on the stationary phase was not observed.
Consequently, the resolution could not be reproduced either on the other
stationary phase modified with C18, phenyl, or phenylhexyl moiety under the same
chromatographic conditions or under the aqueous elution.
PMID- 29955228
TI - Modern Endoscopic Imaging in Diagnosis and Surveillance of Inflammatory Bowel
Disease Patients.
AB - Endoscopy remains the most important diagnostic and monitoring modality in the
management of inflammatory bowel disease. Advances in imaging have progressively
added new tools into the armamentarium of endoscopists with the goal of more
accurate, sensitive, and accessible visual diagnoses for the benefit of patients
with gastrointestinal diseases. Here, we review the relevant literature regarding
commonly used endoscopic techniques (dye-based and digital chromoendoscopy, high
definition endoscopy, capsule endoscopy, and endosonography), as well as advanced
and experimental technologies (full-spectrum endoscopy, endocytoscopy,
autofluorescence, laser endoscopy, and endomicroscopy, including molecular
imaging), applicable to inflammatory bowel diseases and emerging for
implementation into everyday practice. Additionally, we discuss future directions
and techniques as candidates for a superior inflammation imaging in the diagnosis
and prediction of therapeutic response.
PMID- 29955230
TI - Comparison of the Antimicrobial Efficacy of Various Contact Lens Solutions to
Inhibit the Growth of Pseudomonas aeruginosa and Staphylococcus aureus.
AB - Soft contact lenses provide perfect conditions for the breeding of pathogens. The
study is a prospective, experimental study, conducted to know the antimicrobial
ability of multipurpose contact lens solution against standard strains of
Staphylococcus aureus and Pseudomonas aeruginosa by the stand-alone test. The
test method is based on the procedures in the ISO 14729 standard primary stand
alone test. Three multipurpose contact lens care solutions commercially available
in Mangalore markets, namely, Biotrue (Bausch & Lomb), Opti-Free Replenish
(Alcon), and Aquasoft (Stericon Pharma), were tested for its antimicrobial effect
in the microbiology lab at Kasturba Medical College, Mangalore. According to this
study, the solutions named "Biotrue" and "Aquasoft" met the primary stand-alone
and reached the 3log reduction and 5log reduction criteria in the manufacturer
recommended time, respectively. No conclusion could be drawn for Opti-Free
Replenish since the minimum recommended disinfection time was overnight, whereas
it was noted for 6 hr only, and it should have been experimented further. The
effectiveness of multipurpose solutions varies against different bacterial
species. We have observed that the antimicrobial activity of different solutions
varies with respect to time of incubation, and also there was a marked difference
in the activity of some solutions against S. aureus and P. aeruginosa. So, it is
necessary for the contact lens users to store their lenses in solutions for
longer duration of hours. It is also recommended to use solutions that clear the
ISO 14729 standards for better health conditions of the eye.
PMID- 29955231
TI - Undifferentiated Pleomorphic Sarcoma of Pancreas: A Case Report and Review of the
Literature for the Last Updates.
AB - The most prevalent type of soft tissue sarcoma is undifferentiated pleomorphic
sarcoma (UPS) or previously known as malignant fibrous histiocytoma. It accounts
over 20% of all soft tissue sarcomas and occurs most frequently in the
extremities, trunk, and retroperitoneum. However, it has been rarely observed in
the digestive system. Pancreas sarcoma represents less than 1% of all pancreatic
tumors, and primary UPS of the pancreas is even rarer. It exhibits high
recurrence and poor prognosis. In this case, a 72-year-old woman with a UPS tumor
which was located in the pancreas head and neck without adhesion to the
retroperitoneum will be discussed.
PMID- 29955232
TI - Marrow Adipose Tissue: Its Origin, Function, and Regulation in Bone Remodeling
and Regeneration.
AB - Marrow adipose tissue (MAT) is a unique fat depot in the bone marrow and exhibits
close relationship with hematopoiesis and bone homeostasis. MAT is distinct from
peripheral adipose tissue in respect of its heterogeneous origin, site-specific
distribution, and complex and perplexing function. Though MAT is indicated to
function in hematopoiesis, skeletal remodeling, and energy metabolism, its
explicit characterization still requires further research. In this review, we
highlight recent advancement made in MAT regarding the origin and distribution of
MAT, the local interaction with bone homeostasis and hematopoietic niche, the
systemic endocrine regulation of metabolism, and MAT-based strategies to enhance
bone formation.
PMID- 29955233
TI - Risk Factors for Hemorrhagic and Ischemic Stroke in Sub-Saharan Africa.
AB - Introduction: In sub-Saharan Africa (SSA), there is a significant burden of
ischemic stroke (IS) and hemorrhagic stroke (HS), although data on risk factors
for each type are sparse. In this systematic review we attempt to characterize
the risk factors. Methods: We systematically reviewed (PubMed, EMBASE, WHOLIS,
Google Scholar, Wiley online, and the Cochrane Central Register of Controlled
Trials (CENTRAL)) case-control studies and case series from 1980 to 2016 that
reported risk factors for IS and/or HS in SSA. For each risk factor we calculated
random-effects pooled odds ratios (ORs) for case-control studies and pooled
prevalence estimates for case series. Results. We identified 12 studies,
including 4,387 stroke patients. Pooled analysis showed that patients who had
diabetes (OR = 2.39; 95% CI: 1.14-5.03) and HIV (OR = 2.46 (95% CI: 1.59-3.81)
were at a significantly greater risk of suffering from all stroke types. There
were insufficient data to examine these factors by stroke type. Among case
series, the pooled prevalence of hypertension was higher for HS than for IS
(73.5% versus 62.8%), while diabetes mellitus (DM) and atrial fibrillation (AF)
were more prevalent among IS compared to HS (15.9% versus 10.6% and 9.6% versus
2.3%, respectively). Conclusions: There remain too few data from SSA to reliably
estimate the effect of various factors on the risk of IS and HS. Furthermore, the
vast majority of cases were identified in hospital and so are unlikely to be
representative of the totality of stroke cases in the community.
PMID- 29955234
TI - Efficacy and Safety of Auricular Acupuncture for Cognitive Impairment and
Dementia: A Systematic Review.
AB - Objectives: To analyze the efficacy and safety of auricular acupuncture (AA) in
patients with cognitive impairment and dementia. Methods: Twelve electronic
databases were searched for randomized controlled trials evaluating effects of AA
in patients with cognitive impairment and/or dementia, from their inception to
August 2017. The primary outcome was cognitive function, and secondary outcomes
were self-care ability, quality of life, clinical efficacy rate, and incidences
of adverse events. Results: Nine studies were included, and five involving 677
participants were analyzed quantitatively. Compared with Western medications
(WM), AA had mixed effects on cognitive functions (Mini-Mental State Examination
[MMSE], mean difference [MD] 0.73, 95% confidence interval [CI] -0.02 to 1.48;
Hierarchic Dementia Scale [HDS], MD 2.21, 95% CI 1.09 to 3.33); there was no
significant improvement in the activities of daily living (ADL) score (MD 0.20,
95% CI -3.51 to 3.91) in patients with vascular dementia (VD). Compared to WM, AA
combined with WM showed better clinical efficacy rate (risk ratio [RR] 1.42, 95%
CI 1.06 to 1.91) in patients with VD; there was no significant improvement in
cognitive functions (MMSE, MD 0.97, 95% CI -0.44 to 2.38; Montreal Cognitive
Assessment [MoCA], MD 0.22, 95% CI -1.83 to 2.27) in patients with mild cognitive
impairment (MCI). Compared to herbal medicine (HM), AA plus HM showed significant
improvements in cognitive function (MMSE, MD 1.31, 95% CI 0.13 to 2.49) in
patients with MCI and patients with vascular cognitive impairment, no dementia
(VCIND) and in ADL score (MD -6.70, 95% CI -8.78 to -4.62) in patients with MCI.
No adverse event associated with AA was reported. Conclusion: The evidence
reveals mixed efficacy of AA in patients with cognitive impairment and/or
dementia. However, the results were inconclusive because of the small number and
poor methodological quality of the included studies.
PMID- 29955235
TI - Effects of Chailong Jieyu Pill on Behavior, Monoamine Neurotransmitters, and
Corticosteroid Receptors in a Rat Model of Anxiety Disorder.
AB - Chailong Jieyu Pill (CJP) is composed of Radix Bupleuri, Radix Scutellariae,
Rhizoma Pinelliae Preparata, Radix Codonopsis, Radix Glycyrrhizae preparata,
keel, Concha Ostreae, Concha Margaritifera Usta, Rhizoma Zingiberis Recens, and
Fructus Jujubae. CJP has shown good clinical effects on improving anxiety
disorders. However, as the mechanism underlying such benefits remains unclear,
the aim of this study was to investigate the mechanism of action for CJP on
anxiety-related behaviors in a rat model of anxiety disorder. After establishing
a rat model of anxiety disorder using uncertain empty bottle stimulation, rats
were divided into control, model, citalopram, low-dose CJP, and high-dose CJP
groups. After 1 month of administration, effects of treatments on rat appearance,
body weight, and open-field test scores were observed. In addition, hippocampal
monoamine neurotransmitter (5-hydroxytryptamine, dopamine, and norepinephrine)
contents were measured with an enzyme-linked immunosorbent assay, and mRNA
expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR)
were measured with reverse transcription-polymerase chain reaction. CJP increased
rat weight, and this effect was increased in the high-dose CJP group compared
with the citalopram group (P < 0.05). CJP also elevated open-field test scores
compared with the citalopram group (P < 0.05). While CJP decreased monoamine
neurotransmitter contents in rat hippocampus, the regulatory effect of CJP on 5
hydroxytryptamine was reduced compared with citalopram (P < 0.01). CJP
upregulated GR mRNA expression in both low-dose (P < 0.05) and high-dose (P <
0.01) CJP groups, but only the latter significantly downregulated MR mRNA
expression and showed enhanced effects compared with citalopram (P < 0.05). Thus,
CJP likely exerted its significant antianxiety effect by diminishing monoamine
neurotransmitters and regulating mRNA expression of MR and GR in the hippocampus
of our rat model of anxiety disorder.
PMID- 29955236
TI - Correlation Analysis between Traditional Chinese Medicine Syndromes and
Gastrointestinal Bleeding after Percutaneous Coronary Intervention.
AB - Objective: To explore the characters of traditional Chinese medicine (TCM)
syndromes after percutaneous coronary intervention (PCI) and to provide syndrome
study theoretical evidence for TCM differentiation treatment after PCI through
retrospective study. Methods: Patients with coronary heart disease (CHD) who
underwent PCI in Cardiovascular Intervention Center of Wangjing Hospital during
Dec. 2012 to Dec. 2014 and met the inclusion criteria were enrolled.
Retrospective study was then conducted based on patients' clinical document and
angiography data to explore the distribution pattern of TCM syndromes. Results:
801 patients were recruited in the study. TCM syndromes in descending order of
their incidence were Qi deficiency and blood stasis syndrome, heart blood stasis
syndrome, Qi and Yin deficiency syndrome, phlegm and blood stasis syndrome, Qi
stagnation and blood stasis syndrome, Yang asthenia syndrome, heart and kidney
yin deficiency syndrome to cold congeal, and blood stasis syndrome in a more to
less order. Qi deficiency and blood stasis syndrome was in the most (occurring in
298 patients, 37.20%); Qi and Yin deficiency syndrome occurred in 163 patients
(20.35%); heart blood stasis syndrome was shown in 126 patients (15.73%); phlegm
and blood stasis syndrome was shown in 95 patients (11.86%). Conclusion: Qi
deficiency and blood stasis syndrome was closely associated with post-PCI
bleeding, implying that this syndrome might serve as a powerful predictor of GI
bleeding as well as a potential supplement to the current predicting and scoring
system of bleeding such as CRUSADE.
PMID- 29955237
TI - Total Flavones of Rhododendron simsii Planch Flower Protect against Cerebral
Ischemia-Reperfusion Injury via the Mechanism of Cystathionine-gamma-Lyase
Produced H2S.
AB - Total flavones of Rhododendron simsii Planch flower (TFR) have a significant
protective effect against cerebral ischemia-reperfusion injury. However, its
mechanism is unclear. This study investigated the protection of TFR against
cerebral ischemia-reperfusion injury via cystathionine-gamma-lyase- (CSE-)
produced H2S mechanism. CSE-/- mice and CSE-siRNA-transfected rat were used.
Relaxation of cerebral basilar artery (CBA), H2S, and CSE mRNA were measured. TFR
significantly inhibited cerebral ischemia-reperfusion-induced abnormal
neurological symptom and cerebral infarct in the normal rats and the CSE+/+ mice,
but not in the CSE-/- mice, and the inhibition was markedly attenuated in CSE
siRNA-transfected rat; TFR elicited a significant vasorelaxation in rat CBA, and
the relaxation was markedly attenuated by removal of endothelium or CSE-siRNA
transfection or coapplication of NO synthase inhibitor L-NAME and PGI2 synthase
inhibitor Indo. CSE inhibitor PPG drastically inhibited TFR-evoked vasodilatation
resistant to L-NAME and Indo in endothelium-intact rat CBA. TFR significantly
increased CSE mRNA expression in rat CBA endothelial cells and H2S production in
rat endothelium-intact CBA. The increase of H2S production resistant to L-NAME
and Indo was abolished by PPG. Our data indicate that TFR has a protective effect
against the cerebral ischemia-reperfusion injury via CSE-produced H2S and
endothelial NO and/or PGI2 to relax the cerebral artery.
PMID- 29955238
TI - Bioactivity-Guided Isolation of Neuritogenic Factor from the Seeds of the Gac
Plant (Momordica cochinchinensis).
AB - Nerve growth factor (NGF) is an endogenously produced protein with the capacity
to induce central nervous system (CNS) neuronal differentiation and repair. NGF
signaling involves its binding to tropomyosin-related kinase (Trk) receptors,
internalization, and initiation of phosphorylation cascades which cause
microtubule reorganization and neuronal outgrowth. Because NGF cannot cross the
blood-brain barrier, its therapeutic use is limited. Synthetic peptides that can
act as NGF receptor agonists (NGF mimetics) are known to attenuate
neurodegenerative pathologies in experimental models of Alzheimer's disease and
Parkinson's disease; however, the existence of plant-based NGF mimetics is
uncertain. For this reason, we recently completed a high throughput screening of
over 1100 nutraceuticals (vitamins, herbal plant parts, polyphenolics, teas,
fruits, and vegetables) to identify neuritogenic factor using a PC-12 cell model.
Remarkably we found only one, commonly known as the seed of Gac plant (Momordica
cochinchinensis) (MCS). In the current study, we further investigated this seed
for its neuritogenic effect using bioactivity-guided chemical separations. The
data show no biological neuritogenic activity in any chemical solvent fraction,
where activity was exclusive to the crude protein. MSC crude proteins were then
separated by 1D electrophoresis, where the active neuritogenic activity was
confirmed to have a molecular mass of approximately 17 kDa. Subsequently, the
17kDa band was excised, digested, and run on a UPLC-MS/MS with a Q Exactive
Hybrid Quadrupole-Orbitrap Mass Spectrometer with data evaluated diverse tools
such as X! Tandem, OMS, and K-score algorithms. Proteomic evaluation of the 17kDa
band confirmed evidence for 11S globulin subunit beta, napin, oleosin, Momordica
trypsin inhibitors (TI) MCoTI-I /II, and many isoforms of Two Inhibitor Peptide
Topologies (TIPTOPs). While all peptides identified correspond to the
genus/species, Momordica cochinchinensis and Cucumis Sativus, a significant
limitation of the analysis is the nonexistence of full annotation for the
Momordica cochinchinensis proteome. In conclusion, these findings demonstrate
that there is a stable protein within MCS having a mass of 17kDa with the
capacity to induce neurite outgrowth. Future work will be required to establish
the therapeutic value of the MCS for the treatment of neurodegenerative diseases.
PMID- 29955239
TI - Successful retrograde recanalization of an acute iatrogenic venous graft
occlusion through the previously stented coronary anastomosis in a patient with
non-ST elevation myocardial infarction.
PMID- 29955240
TI - Hepatic epithelioid angiomyolipoma with renal metastasis: radiologic-pathologic
correlation.
AB - Epithelioid angiomyolipoma (EAML) is a rare subtype of angiomyolipomas. Unlike
the conventional angiomyolipomas, EAML often contains minimal fat which usually
precludes prospective diagnosis on imaging. The imaging findings of EAML may
overlap with other benign and malignant hepatic neoplasms. We report a hepatic
epithelioid angiomyolipoma in a 47-year-old female which metastasized to the
right kidney and recurred after resection in the liver. We analyze the imaging
findings of EAML on ultrasound, computed tomography, positron emission tomography
and magnetic resonance imaging. Correlation between the imaging and
histopathologic findings is made. The estimated annual growth and doubling time
of the primary hepatic EAML are calculated. To the best of our knowledge, this is
the first published report of positron emission tomography-computed tomography
findings and annual growth rate for hepatic EAML.
PMID- 29955241
TI - Spontaneous intracranial hypotension complicated by cerebral venous thrombosis.
AB - Spontaneous intracranial hypotension (SIH) is a well-known cause of orthostatic
headache. Although subdural fluid collection is a usual complication of SIH, SIH
as a risk factor for cerebral venous thrombosis (CVT) is not well-known. There
are several mechanisms that could contribute to the development of CVT in SIH.
Herein, we report a case of a 33-year-old woman with SIH complicated by CVT. She
was treated with anticoagulation but did not receive a blood patch for the SIH,
because there was resolution of orthostatic headache with bed rest and sufficient
hydration. Follow-up magnetic resonance imaging showed resolution of the findings
of SIH and CVT. Patients with SIH should be closely observed for any change in
the headache pattern, which might suggest the development of CVT.
PMID- 29955242
TI - Side-to-side bowel anastomosis mimicking intussusception in a 2-year-old child
with Peutz-Jeghers syndrome.
AB - Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited condition
characterized by hamartomatous gastrointestinal polyps, mucocutaneous
pigmentation, and a predisposition for malignancy. Most patients with PJS are
diagnosed in the second or third decade of life, and commonly have
intussusception as a complication. This report describes an unusual case of a 2
year-old male known to have PJS, who had previously developed a small bowel
intussusception caused by a polyp requiring a very short segmental small bowel
resection. The patient remained asymptomatic several months after the surgery and
then presented with acute abdominal discomfort. On abdominal ultrasound, a target
sign measuring 2.7 cm was noted in the left upper quadrant of the abdomen,
suggesting a small bowel-small bowel intussusception. There was no evidence of
intussusception or bowel obstruction otherwise on diagnostic laparoscopy. It was
thought that the previous side-to-side anastomosis had mimicked intussusception
on the ultrasound examination. A repeat abdominal ultrasound was performed 1 week
after the laparoscopy when the patient was asymptomatic. This again demonstrated
a target sign identical in appearance to the previous ultrasound and confirmed
that the side-to side anastomosis had in fact mimicked intussusception. It is
important that the pediatric gastroenterology, radiology, and surgery communities
are aware of this ultrasound finding; it could impact the decision on whether to
operate emergently. To our knowledge this is the first report describing this
unusual scenario in humans.
PMID- 29955243
TI - Spin Relays Enable Efficient Long-Range Heteronuclear Signal Amplification By
Reversible Exchange.
AB - A systematic experimental study is reported on the polarization transfer to
distant spins, which do not directly bind to the polarization transfer complexes
employed in Signal Amplification By Reversible Exchange (SABRE) experiments.
Both, long-range transfer to protons and long-range transfer to heteronuclei i.e.
13C and 15N are examined. Selective destruction of hyperpolarization on 1H, 13C,
and 15N sites is employed, followed by their re-hyperpolarization from
neighboring spins within the molecules of interest (pyridine for 1H studies and
metronidazole-15N2-13C2 for 13C and 15N studies). We conclude that long-range
sites can be efficiently hyperpolarized when a network of spin-1/2 nuclei enables
relayed polarization transfer (i.e. via short-range interactions between sites).
In case of proton SABRE in the milli-Tesla regime, a relay network consisting of
protons only is sufficient. However, in case 13C and 15N are targeted (i.e. via
SABRE in SHield Enables Alignment Transfer to Heteronuclei or SABRE-SHEATH
experiment), the presence of a heteronuclear network (e.g. consisting of 15N)
enables a relay mechanism that is significantly more efficient than the direct
transfer of spin order from para-H2-derived hydrides.
PMID- 29955244
TI - Spin-Lattice Relaxation of Hyperpolarized Metronidazole in Signal Amplification
by Reversible Exchange in Micro-Tesla Fields.
AB - Simultaneous reversible chemical exchange of parahydrogen and to-be
hyperpolarized substrate on metal centers enables spontaneous transfer of spin
order from parahydrogen singlet to nuclear spins of the substrate. When performed
at sub-micro-Tesla magnetic field, this technique of NMR Signal Amplification by
Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE
SHEATH). SABRE-SHEATH has been shown to hyperpolarize nitrogen-15 sites of a wide
range of biologically interesting molecules to a high polarization level (P >
20%) in one minute. Here, we report on a systematic study of 1H, 13C and 15N spin
lattice relaxation (T1) of metronidazole-13C2-15N2 in SABRE-SHEATH
hyperpolarization process. In micro-Tesla range, we find that all 1H, 13C and 15N
spins studied share approximately the same T1 values (ca. 4 s at the conditions
studied) due to mixing of their Zeeman levels, which is consistent with the model
of relayed SABRE-SHEATH effect. These T1 values are significantly lower than
those at higher magnetic (i.e. the Earth's magnetic field and above), which
exceed 3 minutes in some cases. Moreover, these relatively short T1 values
observed below 1 micro-Tesla limit the polarization build-up process of SABRE
SHEATH- thereby, limiting maximum attainable 15N polarization. The relatively
short nature of T1 values observed below 1 micro-Tesla is primarily caused by
intermolecular interactions with quadrupolar iridium centers or dihydride protons
of the employed polarization transfer catalyst, whereas intramolecular spin-spin
interactions with 14N quadrupolar centers have significantly smaller
contribution. The presented experimental results and their analysis will be
beneficial for more rational design of SABRE-SHEATH (i) polarization transfer
catalyst, and (ii) hyperpolarized molecular probes in the context of biomedical
imaging and other applications.
PMID- 29955245
TI - Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease
Progression.
AB - Cholesterol is the only lipid whose absorption in the gastrointestinal tract is
limited by gate-keeping transporters and efflux mechanisms, preventing its rapid
absorption and accumulation in the liver and blood vessels. In this review, I
explored the current data regarding cholesterol accumulation in liver cells and
key mechanisms in cholesterol-induced fatty liver disease associated with the
activation of deleterious hypoxic and nitric oxide signal transduction pathways.
Although nonalcoholic fatty liver disease (NAFLD) affects both obese and nonobese
individuals, the mechanism of NAFLD progression in lean individuals with healthy
metabolism is puzzling. Lean NAFLD individuals exhibit normal metabolic
responses, implying that liver damage is not associated with impaired metabolism
per se and that direct lipotoxic effects are crucial for disease progression.
Several redox and oxidant signaling pathways involving cholesterol are at play in
fatty liver disease development. These include impairment of the mitochondrial
and lysosomal function by cholesterol loading of the inner-cell membranes;
formation of cholesterol crystals and hepatocyte degradation; and crown-like
structures surrounding degrading hepatocytes, activating Kupffer cells, and
evoking inflammation. The current review focuses on the induction of liver
inflammation, fibrosis, and steatosis by free cholesterol via the hypoxia
inducible factor 1alpha (HIF-1alpha), a main oxygen-sensing transcription factor
involved in all stages of NAFLD. Cholesterol loading in hepatocytes can result in
chronic HIF-1alpha activity because of the decreased oxygen availability and
excessive production of nitric oxide and mitochondrial reactive oxygen species.
PMID- 29955248
TI - Intrinsic vulnerability assessment of shallow aquifers of the sedimentary basin
of southwestern Nigeria.
AB - The shallow groundwater of the multi-layered sedimentary basin aquifer of
southwestern Nigeria was assessed based on its intrinsic vulnerability property.
The vulnerability evaluation involves determining the protective cover and
infiltration condition of the unsaturated zone in the basin. This was achieved
using the PI (P stands for protective cover effectiveness of the overlying
lithology and I indicates the degree of infiltration bypass) vulnerability method
of the European vulnerability approach. The PI method specifically measures the
protection cover and the degree to which the protective cover is bypassed.
Intrinsic parameters assessed were the subsoil, lithology, topsoil, recharge and
fracturing for the protective cover. The saturated hydraulic conductivity of
topsoil, infiltration processes and the lateral surface and subsurface flow were
evaluated for the infiltration bypassed. The results show moderate to very low
vulnerability areas. Low vulnerability areas were characterised by lithology with
massive sandstone and limestone, subsoils of sandy loam texture, high slopes and
high depth to water table. The moderate vulnerability areas were characterised by
high rainfall and high recharge, low water table, unconsolidated sandstones and
alluvium lithology. The intrinsic vulnerability properties shown in vulnerability
maps will be a useful tool in planning and monitoring land use activities that
can be of impact in groundwater pollution.
PMID- 29955246
TI - The Electrical Stimulation of the Bed Nucleus of the Stria Terminalis Causes
Oxidative Stress in Skeletal Muscle of Rats.
AB - Recent studies indicate that activation of hypothalamus-pituitary-adrenocortical
axis (HPA) plays the crucial role in stress response, while several lines of
evidence mark the bed nucleus of the stria terminalis (BST) as a major mediator
of the HPA axis responses to stress. The purpose of this study was to investigate
the influence of the corticosterone flux induced by the electrical stimulation of
BST on markers of free radical damage of lipids and proteins and antioxidant
enzyme activity in skeletal muscle of rats. The male Wistar rats were used and
assigned to one of three groups: sham-operated (SHM; n = 6), two-week (ST2; n =
6), and four-week stimulated (ST4; n = 5) groups. Blood, soleus, and extensor
digitorum longus muscles were collected. The chronic, 4-week electrical
stimulation of the BST evokes increased plasma corticosterone concentration,
which resulted in oxidative stress in skeletal muscles. We found higher level of
lipid peroxidation markers, lower level of protein oxidation marker, and elevated
antioxidant enzyme activity in both muscles. Our findings have also potential
implication showing that reaction to the long-term "psychological stress" may
lead to free radical damage of muscle.
PMID- 29955249
TI - Community resilience to floods in the coastal zone for disaster risk reduction.
AB - The northern coast of the Central Java province is considered to be the critical
area of flood path. The area is vulnerable to floods because of incessant rain
and/or sea-level rise, resulting in suffering to people and the deterioration of
the ecosystem. A number of measures have been implemented to manage the problem
of floods, although the results are not noteworthy. It is obvious that
infrastructure capacity for flood control, community awareness and other multiple
factors significantly contribute to averting the problem of flooding in the area.
This study aimed to determine the level of flood-zone vulnerability, the level of
community resilience to floods and the influence of vulnerability aspects on
community resilience. Interviews were conducted to outline the resilience model.
A quantitative method was employed to analyse the data. The results of this study
indicated that the exposure aspect is the greatest variable in describing flood
vulnerability. At the same time, the greatest variables determining community
resilience are damages, followed by losses and personal casualties. Among the
flood vulnerability aspects are the exposure and adaptive capacities that
determine the community resilience of the northern coast of Central Java.
PMID- 29955247
TI - BAG3 Protein Is Involved in Endothelial Cell Response to Phenethyl
Isothiocyanate.
AB - Phenethyl isothiocyanate (PEITC), a cruciferous vegetable-derived compound, is a
versatile cancer chemopreventive agent that displays the ability to inhibit tumor
growth during initiation, promotion, and progression phases in several animal
models of carcinogenesis. In this report, we dissect the cellular events induced
by noncytotoxic concentrations of PEITC in human umbilical vein endothelial cells
(HUVECs). In the early phase, PEITC treatment elicited cells' morphological
changes that comprise reduction in cell volume and modification of actin
organization concomitantly with a rapid activation of the PI3K/Akt pathway.
Downstream to PI3K, PEITC also induces the activity of Rac1 and activation of c
Jun N-terminal kinase (JNK), well-known regulators of actin cytoskeleton
dynamics. Interestingly, PEITC modifications of the actin cytoskeleton were
abrogated by pretreatment with JNK inhibitor, SP600125. JNK signaling led also to
the activation of the c-Jun transcription factor, which is involved in the
upregulation of several genes; among them is the BAG3 protein. This protein, a
member of the BAG family of heat shock protein (Hsp) 70 cochaperones, is able to
sustain survival in different tumor cell lines and neoangiogenesis by directly
regulating the endothelial cell cycle. Furthermore, BAG3 is involved in
maintaining actin folding. Our findings indicate that BAG3 protein expression is
induced in endothelial cells upon exposure to a noncytotoxic concentration of
PEITC and its expression is requested for the recovery of normal cell size and
morphology after the stressful stimuli. This assigns an additional role for BAG3
protein in the endothelial cells after a stress event.
PMID- 29955251
TI - Adaptation measures to sustain indigenous practices and the use of indigenous
knowledge systems to adapt to climate change in Mutoko rural district of
Zimbabwe.
AB - This article examines adaptation measures used to sustain indigenous practices
and the use of indigenous knowledge systems (IKS) to adapt to climate change in
Mutoko rural district of Zimbabwe. Community-based adaptation is able to reduce
the vulnerability as well as improve the resilience of the local people to
climatic variability and change. Subsistence farmers have always adopted adaptive
strategies to some of these changes over the years. As such, the adoption of
indigenous practices will significantly help rural community members to adapt to
climate change. This study employed a qualitative method and an exploratory
design, and the results are derived from 30 purposively selected in-depth
interviews. The study discovered that there are numerous measures used to adapt
to climate change and subsequently to sustain indigenous practices. The study
also found that the community no longer grows maize in large quantities, having
shifted to millet and sorghum in order to adapt to climate change. The community
also provided various strategies to adapt to climate change. These strategies
include mulching, creating large storage houses for produce and creating
temporary walls on riverbanks in order to store water when the rivers dry up.
This study concludes that climate change adaptation measures employed by the
community have significantly helped them to sustain their indigenous practices in
many ways. Also, the use of IKS, through activities such as crop type change from
maize to traditional millet and sorghum (which facilitates traditional lifestyle
and activities), re-establishes the community's indigenous practices since they
are made to observe the practices of yesteryear.
PMID- 29955250
TI - Access to energy sources in the face of climate change: Challenges faced by women
in rural communities.
AB - Access to energy is a challenge to rural communities, especially among women who
are the prime household energy users. This article is based on research carried
out in the Tswapong villages in Botswana where energy sources particularly wood,
are slowly getting depleted while electricity connection costs remain
unaffordable for the poor. The article provides constructivist analysis of
experiences in real-life situations among women. Data were generated through
observations, documents analysis, interviews and focus group discussions. It has
emerged from the research that majority of the respondents use firewood as energy
source. Firewood and gas are mainly used for cooking while electricity is mainly
used for lighting. The demand for firewood has led to firewood commercialisation,
the depletion of preferred firewood tree species and increase in the impact of
climate change. The article recommends economic diversification and subsidies to
empower the majority of the rural poor to connect to the national electric grid
and reduce on firewood dependence. These could be complemented by harnessing of
solar energy and low-cost, energy-saving technologies. Subsidies to enable women
access to energy services would contribute immensely to the decade of Sustainable
Energy for All and to the attainment of the post 2015 sustainable development
goal on energy.
PMID- 29955252
TI - Managing wetlands for disaster risk reduction: A case study of the eastern Free
State, South Africa.
AB - This article investigated the knowledge and practice of a nature-based solution
to reduce disaster risks of drought, veld fires and floods using wetlands in the
eastern Free State, South Africa. A mixed research method approach was used to
collect primary data using three data collection tools, namely questionnaires,
interviews and field observations. Ninety-five wetlands under communal and
private ownership as well as a few in protected areas were sampled, with their
users completing questionnaires. The study showed that communal wetlands were
more degraded, while wetlands in protected areas and in private commercial farms
were in a good ecological state. An extensive literature review reveals that
healthy wetlands are effective buffers in reducing disaster risks such as
drought, veld fires and floods which are recurrent in the study area. Therefore,
through better land-use and management practices, backed by education and
awareness, wetlands could be good instruments to mitigate recurrent natural
hazards in the agriculturally dominated eastern Free State in South Africa.
PMID- 29955253
TI - Social and structural vulnerability as a barrier in HIV and/or AIDS communication
campaigns: Perceptions of undergraduate students at a South African tertiary
institution.
AB - The multicultural nature of a higher academic institution comprising students
from different backgrounds can either negatively or positively influence student
behaviour. Students might engage in high-risk practices, which in turn can make
them vulnerable to HIV infection. Higher academic institutions are then tasked
with finding strategies that can help to reduce this risk and vulnerability to
HIV and/or AIDS. However, there are many issues and barriers, both from the
institution and students, which can impede the success of any communication
strategy. The University of the Free State's main campus was selected for this
study. A sample of 402 students from a total of 17 591 undergraduate students
participated in the study. A structured questionnaire was randomly distributed to
the undergraduate students. The sample was compiled across all faculties, as well
as on campus and off campus. A transact walk on campus with an observation
checklist was also used for triangulation purposes. The observation checklist
helped to collect data on the visibility of male and female condoms in toilet
facilities, and HIV and/or AIDS information on noticeboards, bins, stationery,
billboards, etc. The main finding indicated that students were not knowledgeable
about HIV and/or AIDS campaigns rolled out on campus. To support this, the
observational transact walk results indicated that there were no visible
campaigns on campus. Also, problems with existing communication and
organisational barriers were found not only with the students but also with the
implementation office. This study recommends that the university needs to engage
with the students by identifying the root cause of their vulnerability. The
university should explore and make use of all the available resources for a
successful intervention, thereby building students' resilience in preventing HIV
infection.
PMID- 29955254
TI - Economic migration and the socio-economic impacts on the emigrant's family: A
case of Ward 8, Gweru Rural district, Zimbabwe.
AB - Gweru Rural district in the Midlands province of Zimbabwe has witnessed an
increasing number of outward migrations of breadwinners, leaving behind a
desperate environment for families. This study was motivated by the realisation
that most of the sick left behind, the elderly and children would visit the
health centres unaccompanied, risking taking prescribed drugs incorrectly, thus
further compromising their health. The study sought to establish the socio
economic effects of international migration on family members left behind in ward
8 of Gweru Rural. The study adopted a qualitative case study approach. Focus
group discussions, questionnaires and structured individual interviews were used
to elicit for data. Non-probability sampling design was used because of small
samples available. Convenience and purposive sampling techniques were
particularly used. Data were manually analysed and presented both qualitatively
and quantitatively. The study revealed that international migration particularly
to South Africa, especially by non- professionals, was not yielding the much
expected economic gains; instead it was characterised by more negative social
effects on the emigrant's family. The study recommends that emigrants should
consider migrating with their loved ones and, where it is not feasible, to put in
place sound alternative caregiving arrangements. The study has provided an
insight into international migration and its effects on left-behind families.
However, a more comprehensive and quantitative survey remains critical to delving
deeper into this migration phenomenon, particularly on how both the emigrant and
left-behind spouses handle the issue of conjugal rights.
PMID- 29955255
TI - The political ecology of stakeholder-driven climate change adaptation: Case study
from Ntalale ward, Gwanda district, in Zimbabwe.
AB - Vulnerable rural communities face climate change-related shifts in rainfall
patterns, particularly droughts and floods. The study investigated how Ntalale
ward households in Gwanda district of Zimbabwe interpret climate change and adapt
to its stressors in the context of the Zimbabwean political economy. Focus group
discussions and interviews collected qualitative data. The community has
experienced the following climate change-related risks: droughts, floods,
heatwave and intra-seasonal rainfall variability. Droughts were reported to be
occurring more frequent in the past 25 years as compared to the period before
1991. Ntalale area experienced floods in the 2002-2003 rainy season only.
Respondents generally perceived that the rainy season had changed in the past 5
years, with the season now beginning in December and ending in March. The
households have resorted to shifting cultivation practices, replanting, use of
wetlands in preference to upland fields, changing of seed varieties or crops,
selling of livestock and informal trading as coping strategies. Although non
governmental organisations have assisted the community to set up irrigation
schemes, a few selected community members have benefited from the initiative. The
Ntalale community has experienced four climate change-related risks and
institutions have assisted the community. It is recommended that cooperation
between households and institutions is key in developing stakeholder-driven
adaptation strategies.
PMID- 29955256
TI - Making space for experiential knowledge in climate change adaptation? Insights
from municipal planning officers in Bohol, Philippines.
AB - Climate change is a global phenomenon that has multiple local effects on people
and places. Yet, climate change knowledge often travels uncomfortably across
scales and needs constant re-interpretation as it is applied in different spatial
contexts. This requires the examination of how scientific and local knowledge
about climate change travel across social systems and shape local meanings and
adaptive actions on climate change. Using an interpretive social science analysis
of environmental change, this study investigates development planning as a key
boundary object for handling both kinds of knowledge and explores experiential
knowledge of climate change held by planning officers from the coastal landscape
of the island province of Bohol, Philippines. Drawing upon face-to-face
interviews, mental maps, and planning documents review, main results first
characterise three experiential ways of knowing about climate change across
spaces of lived experiences and spaces of maps and plans. Then, we show how
planners engage with climate change adaptation by combining national, techno
scientific and local, on-the-ground ways of knowing, offering a venue in which
experiential knowledge on climate change is used for building planning
significance and making more grounded accounts of adaptation moving forward in
planning policy and practice.
PMID- 29955257
TI - The effectiveness of community-based rehabilitation as a strategy for improving
quality of life and disaster resilience for children with disability in rural
Zimbabwe.
AB - The study aimed to investigate the effectiveness of the community-based
rehabilitation (CBR) project in Ward 20 of Chipinge in Zimbabwe and ascertain the
positive district changes in the quality of life and disaster resilience of
children with disability. Effectiveness involved examining the role of the
parents of children with disabilities and the general community in the CBR
programme, the extent to which children living with disabilities (CWDs) have been
empowered to live quality life and access basic social services and evaluate
whether local resources and capacities were being utilised. Data were collected
through key informant interviews, document analysis and focus group discussions.
The CBR model borrows heavily from rights-based approaches to development. Its
practical application is problematic because of difficulties in defining issues
such as participation and the ability of developing and poor communities to
generate resources for these programmes. The study found that factors that hinder
the effectives of CBR programmes included continuous dependence on donor funding,
lack of political will by government and local authorities to commit financial
resources towards CBR implementation and unreliable referral systems for access
of services for children with disability. Gaps identified include establishing
appropriate context-specific strategies that suit developing countries. The
government and local authorities should prioritise resource allocation for
marginalised groups such as people with disabilities. Civil society should not be
the major and only source of funding for CBR. Extensive consultations should be
made to adapt the CBR model to the socio-economic context of developing
countries. The referral system for access to services for CWDs should be
strengthened.
PMID- 29955258
TI - Conceptual change of disaster management models: A thematic analysis.
AB - Different models have been proposed for disaster management by researchers and
agencies. Despite their efficiency in some locations, disasters are still a
fundamental challenge in the way of sustainable development. The purpose of this
research is developing a comprehensive conceptual model for disaster management
using thematic analysis. In this regard, first, disaster management models are
collected. In the next stage, the themes of each model are extracted and
categorised in three phases. In the first phase that is descriptive coding,
available elements in each model are extracted as code and the basic themes are
recognised. Then, in the phase of interpretive coding, basic themes are
classified in three categories that are called organising themes (i.e. hazard
assessment, risk management and management actions). In the final phase,
strategic management is selected as the global or overarching theme to integrate
all the other themes. Based on thematic analysis, it can be concluded that
disaster management has three main elements that are the three organising themes.
Therefore, comprehensive model of disaster management should include these three
elements and their sub-basic themes that is called the ideal or criterion type.
Results showed that some scientists have looked at disaster management one
dimensionally (one theme). Even in two-dimensional models, one dimension has
advantage over the other one. While the proposed typology in this study showed
that the comprehensive model should include all the three mentioned elements.
PMID- 29955259
TI - Flooding and poverty: Two interrelated social problems impacting rural
development in Tsholotsho district of Matabeleland North province in Zimbabwe.
AB - Flooding and poverty are the two social problems that have coexisted within the
rural communities of Tsholotsho district. As a result, both problems have
negatively affected and disrupted the everyday pattern of lives of people living
in the district. This study sought to highlight how the two problems combine to
impact human societies. The objectives that the study sought to fulfil were to
establish the impact of flooding on the development of rural communities, to
analyse how poverty manifests itself in rural communities, to analyse the
relationship that exists between flooding and poverty and to suggest ways for
dealing with the two problems. A qualitative research approach, using interviews
and observations, was used to gather data from the research participants. The
study findings were that flooding impeded development through shifting of human
populations, destruction of crops, shelter and livestock. Floods also affected
human capital through causing injuries to members of the community. Poverty
manifested itself in three ways - as a development barrier, a vulnerability
amplifier and a non-discriminatory agent. The study further found that a strong
relationship exists between flooding and poverty because of the fact that
flooding causes or worsens poverty, whereas poverty increases flood
vulnerability. The study concluded that the poor need government assistance to
reconstruct shelter destroyed by floods. Furthermore, programs aimed at improving
livelihoods of the poor are an indispensable imperative. This study informs
policymakers and offers a methodological significance to development and disaster
practitioners. It also adds to the body of literature on flooding and poverty.
PMID- 29955260
TI - Modelling average maximum daily temperature using r largest order statistics: An
application to South African data.
AB - Natural hazards (events that may cause actual disasters) are established in the
literature as major causes of various massive and destructive problems worldwide.
The occurrences of earthquakes, floods and heat waves affect millions of people
through several impacts. These include cases of hospitalisation, loss of lives
and economic challenges. The focus of this study was on the risk reduction of the
disasters that occur because of extremely high temperatures and heat waves.
Modelling average maximum daily temperature (AMDT) guards against the disaster
risk and may also help countries towards preparing for extreme heat. This study
discusses the use of the r largest order statistics approach of extreme value
theory towards modelling AMDT over the period of 11 years, that is, 2000-2010. A
generalised extreme value distribution for r largest order statistics is fitted
to the annual maxima. This is performed in an effort to study the behaviour of
the r largest order statistics. The method of maximum likelihood is used in
estimating the target parameters and the frequency of occurrences of the hottest
days is assessed. The study presents a case study of South Africa in which the
data for the non-winter season (September-April of each year) are used. The
meteorological data used are the AMDT that are collected by the South African
Weather Service and provided by Eskom. The estimation of the shape parameter
reveals evidence of a Weibull class as an appropriate distribution for modelling
AMDT in South Africa. The extreme quantiles for specified return periods are
estimated using the quantile function and the best model is chosen through the
use of the deviance statistic with the support of the graphical diagnostic tools.
The Entropy Difference Test (EDT) is used as a specification test for diagnosing
the fit of the models to the data.
PMID- 29955261
TI - Regional disaster risk management strategies for food security: Probing Southern
African Development Community channels for influencing national policy.
AB - Natural disasters and food insecurity are directly interconnected. Climate change
related hazards such as floods, hurricanes, tsunamis, droughts and other risks
can weaken food security and severely impact agricultural activities.
Consequently, this has an impact on market access, trade, food supply, reduced
income, increased food prices, decreased farm income and employment. Natural
disasters create poverty, which in turn increases the prevalence of food
insecurity and malnutrition. It is clear that disasters put food security at
risk. The poorest people in the community are affected by food insecurity and
disasters; hence, there is a need to be prepared as well as be in a position to
manage disasters. Without serious efforts to address them, the risks of disasters
will become an increasingly serious obstacle to sustainable development and the
achievement of sustainable development goals, particularly goal number 2 'end
hunger, achieve food security and improved nutrition and promote sustainable
agriculture'. In recent years, countries in southern Africa have experienced an
increase in the frequency, magnitude and impact of climate change-related hazards
such as droughts, veld fire, depleting water resources and flood events. This
research aims to reveal Southern African Development Community disaster risk
management strategies for food security to see how they an influence and shape
policy at the national level in southern Africa. Sustainable Livelihood approach
was adopted as the main theoretical framework for the study. The qualitative
Analysis is based largely on data from databases such as national reports,
regional reports and empirical findings on the disaster management-sustainable
development nexus.
PMID- 29955262
TI - Seismic vulnerability assessment to earthquake at urban scale: A case of
Mostaganem city in Algeria.
AB - The focus of this study was the seismic vulnerability assessment of buildings
constituting Mostaganem city in Algeria. Situated 320 km to the west of Algiers,
Mostaganem city encompasses a valuable cultural and architectural built heritage.
The city has suffered several moderate earthquakes in recent years; this has led
to extensive structural damage to old structures, especially unreinforced
historical buildings. This study was divided into two essential steps, the first
step being to establish fragility curves based on a non-linear static pushover
analysis for each typology and height of buildings. Twenty-seven pushover
analyses were performed by means of SAP2000 software (three analyses for each
type of building). The second step was to adopt the US HAZUS software and to
modify it to suit the typical setting and parameters of the city of Mostaganem. A
seismic vulnerability analysis of Mostaganem city was conducted using HAZUS
software after inputting the new parameters of the fragility curves established
within the first step. The results indicated that the number of poor-quality
buildings expected to be totally destroyed under a 5.5 Mw earthquake scenario
could reach more than 28 buildings. Three percent of unreinforced masonry (URM)
buildings were completely damaged and 10% were extensively damaged. Of the
concrete frame buildings, 6% were extensively damaged and 19% were moderately
damaged. According to the built year, 6% of both concrete frame and URM buildings
built before 1980 are estimated to be collapsing. Buildings constructed between
1980 and 1999 are more resistant; 8% of those structures were extensively damaged
and 18% were moderately damaged. Only 10% of buildings constructed after 1999
were moderately damaged. The results also show that the main hospital of the
city, built before 1960, will be extensively damaged during an earthquake of 5.5
Mw. The number of human casualties could reach several hundreds - 10.5% of
residents of URM buildings are injured or dead. Compared with the URM buildings,
concrete frame buildings have lower casualty rates of 1.5% and 0.5% for those
built before and after 1980, respectively. It was concluded that Mostaganem city
belongs to seismic vulnerable zones in Algeria; in this regard, an action plan is
needed for the rehabilitation of old constructions. In addition, the
effectiveness of establishing and introducing new and appropriate fragility
curves was demonstrated.
PMID- 29955263
TI - Climate change and vulnerability discourse by students at a South African
university.
AB - Climate change is expected to pose grave consequences to communities around the
world. It is predicted that many people, mostly in the developing world, will
experience shortages of water and food as well as numerous health-related effects
because of climate change. Therefore, rigorous global action is needed to enable
developing countries to adapt to the effects of climate change. Universities play
a pivotal role in addressing these issues and their impacts through research and
technological innovations. Hence, assessing the extent to which university
students understand climate change and its impacts displays the extent of hope in
mitigating future changes in climatic conditions. This article assesses the
knowledge and understanding of climate change and its impacts by students at an
institution of higher learning in South Africa. This study utilised a
quantitative approach and a descriptive design. The convenience method was used
to obtain participants for the study. Self-administered questionnaires were
utilised in a survey to collect data from the participants. A sample of 90
university students participated in the survey. Data analysis included
descriptive statistics and T-tests. Reliability was measured using the Cronbach's
alpha. The study discovered that university students have low knowledge and
understanding of climate change. As a result, the study concluded that if
students could be well-informed about climate change issues, they could
positively contribute to the development of their communities by crafting smart
climate change mitigation and adaptation skills.
PMID- 29955264
TI - Climate-smart agriculture for sustainable agricultural sectors: The case of
Mooifontein.
AB - Climate change is an environmental phenomenon with the potential to exacerbate
existing disaster risks and cause extensive human, financial and environmental
losses. The Mooifontein agricultural region in South Africa is considered to be a
region vulnerable to climate change-associated risks. These climate risks would
pose a substantial threat to the livelihoods of farmers in the Mooifontein area.
This article aims to explore climate-smart agriculture (CSA) as a resilience
building tool to ensure sustainable agricultural practices. A qualitative
research approach was utilised to gain insights into climate change and the lived
experiences of farmers and agricultural experts in Mooifontein. The findings
revealed that agricultural communities should focus on the identification and
application of adaptation strategies like CSA. The adoption of appropriate CSA
practices will play a vital role in ensuring sustainable livelihoods and improved
community resilience for farming communities in the Mooifontein region.
PMID- 29955265
TI - The contribution of indigenous knowledge to disaster risk reduction activities in
Zimbabwe: A big call to practitioners.
AB - This article examined the contribution of indigenous knowledge to disaster risk
reduction activities in Zimbabwe. The current discourse underrates the use of
indigenous knowledge of communities by practitioners when dealing with
disasters', as the knowledge is often viewed as outdated and primitive. This
study, which was conducted in 2016, sought to examine this problem through
analysing the potential contribution of indigenous knowledge as a useful disaster
risk reduction intervention. Tsholotsho district in Matabeleland, North province
of Zimbabwe, which frequently experiences perennial devastating floods, was used
as a case study. Interviews and researcher observations were used to gather data
from 40 research participants. The findings were that communities understand
weather patterns and could predict imminent flooding after studying trees and
clouds, and the behaviours of certain animal species. Local communities also use
available local resources to put structural measures in place as part of disaster
risk reduction interventions. Despite this important potential, the study found
that the indigenous knowledge of disaster risk reduction of the communities is
often shunned by practitioners. The practitioners claim that indigenous knowledge
lacks documentation, it is not found in all generational classes, it is
contextualised to particular communities and the knowledge cannot be
scientifically validated. The study concluded that both local communities and
disaster risk reduction practitioners can benefit from the indigenous knowledge
of communities. This research has the potential to benefit communities,
policymakers and disaster risk reduction practitioners.
PMID- 29955266
TI - A political economy analysis of decision-making on natural disaster preparedness
in Kenya.
AB - Most deaths from natural disasters occur in low- or middle-income countries;
among them, countries in the Horn of Africa - where Kenya lies. Between September
2015 and September 2016, 23.4 million people in this region faced food insecurity
because of the 2015 El Nino, characterised by floods and droughts. The importance
of effective government decision-making on preparedness and response are critical
to saving lives during such disasters. But this decision-making process occurs in
a political context which is marred by uncertainty with other factors at play.
Yet, good practice requires making investments on a 'no-regrets' basis. This
article looks at the factors influencing Kenya's decision-making process for
natural disasters, the preparedness for the 2015 El Nino as a case study. I
explored what stakeholders understand by 'no-regrets investments' and its
application. I assessed financial allocations by government and donors to
disaster preparedness. Based on key informant interviews, focus group discussions
and financial analyses, this article presents evidence at national and
subnational levels. The findings indicate that in making decisions relating to
preparedness, the government seeks information primarily from sources it trusts -
other government departments, its communities and the media. With no existing
legal frameworks guiding Kenya's disaster preparedness, the coordination of
preparedness is not strong. It appears that there is a lack of political will to
prioritise these frameworks. The no-regrets approach is applied predominantly by
non-state actors. Because there have been 'non-events' in the past, government
has become overcautious in committing resources on a no-regrets basis. Government
allocation to preparedness exceeds donor funding by almost tenfold.
PMID- 29955267
TI - Statistical analysis of annual maximum daily rainfall for Nelspruit and its
environs.
AB - Nelspruit and its environs frequently experience extreme high annual maximum
daily rainfall (AMDR) events resulting in flood hazards. These flood hazards have
caused flood disasters that have resulted in loss of property and lives. The main
objective of this study was to carry out statistical analysis of extreme high
AMDR events that have caused flood hazards, which in turn have caused flood
disasters in Nelspruit and its environs. Empirical continuous probability
distribution functions (ECPDF) and theoretical continuous probability
distribution functions (TCPDF) were applied to carry out the statistical analysis
of the extreme high AMDR events. Annual maximum daily rainfall event of magnitude
100 mm was identified as a threshold. Events > 100 mm were considered as extreme
high events resulting in flood disasters. The results of empirical frequency
analysis showed that the return period of flood disasters was 10 years. The
occurrence probability of flood disaster event at least once in 1, 2, 3, 4 and 5
years was 0.10, 0.19, 0.27, 0.34 and 0.41, respectively. Generalised logistic PDF
was identified as the best-fit theoretical PDF for statistical analysis of the
extreme high AMDR events in Nelspruit and its environs. The results of this study
contributed to the understanding of frequency and magnitude of extreme high AMDR
events that could lead to flood disasters. The results could be applied in
developing flood disaster management strategies in Nelspruit and its environs.
PMID- 29955268
TI - Delineating risk zones and evaluation of shelter centres for flood disaster
management along the Pahang River Basin, Malaysia.
AB - Shelter centres are important locations to safeguard people from helpless
situations and are an integral part of disaster risk reduction (DRR),
particularly for flood DRR. The establishment of shelter centres, and their
design based on scientific assessment, is crucial. Yet, they are very much
related to the geographic location, socio-economic conditions and the livelihoods
of the affected communities. However, many parts of the developing world are
still lagging behind in ensuring such scientific design. Considering the flood
disaster in 2014 that affected the residents living along the Pahang River Basin,
in this study we delineate the communities at risk and evaluate the existing
shelter centres to determine how they reduce people's vulnerability to the risks
associated with rural and urban landscapes. We used spatial analysis tools to
delineate risk zones and to evaluate existing evacuation systems. A flood
disaster risk map was produced to determine which communities are living with
risks. Subsequently, the distribution of shelter centres examined whether they
are able to support people living at the flood risk zones. These centres were
also evaluated using a set of international guidelines for effective disaster
shelters. This reveals that the number of shelter centres is not adequate. The
designation and designing of shelter centres are not being done scientifically.
The maps produced here have a lot of potential to support disaster management
decisions, in particular site selection and the prioritisation of centres. The
study concludes with a set of guidelines and recommendations for structural and
non-structural measures, such as alternative livelihoods and the potential of
ecotourism, which may improve the resilience among flood-affected communities;
and the decision-making process for the overall flood DRR initiatives.
PMID- 29955269
TI - Twenty years of community-based disaster risk reduction experience from a dryland
village in Indonesia.
AB - Academics and practitioners often argue indirectly that all the roads to
community resilience should be paved with community-based disaster risk reduction
(CBDRR) approach. Community-based approach to resilience building has been a
discursive material that appeals many disaster management players including
international donors, non-governmental organisations and high-level government
officials as well as politicians. Some researchers argue that CBDRR is the
foundation of disaster risk governance. Unfortunately, globally, there is lack of
studies on long-term and real-world experience of CBDRR. This article addresses
this research gap by providing insights of CBDRR activities from a village in
eastern Indonesia based on long-term studies. The adoption of CBDRR approach in
Indonesia took place in the late 1990s and the authors have been part of the
early adopters of the framework. Using longitudinal participant observations,
this research combined qualitative and quantitative data collected during 1998
2017. It shows the rise and fall of a community responding to disaster risks over
time. The article further highlights stories of frustrations and celebrations
that surround CBDRR activities implemented by one local community in a dryland
village in eastern Indonesia.
PMID- 29955270
TI - A geographic information system-based approach of flood hazards modelling,
Paschim Medinipur district, West Bengal, India.
AB - From the beginning of civilisation, human beings have preferred living on the
river banks which have been the most vulnerable areas of flood hazards and
consequent disasters. During the monsoon period, in many developing countries of
south-east Asia, flood hazards and disasters have been a serious challenge for
their development. Most of the rivers exceed their normal channel capacity
attaining the flood stage and frequently overflow their banks, causing great
havoc to the life and property of the people. Flooding is a very serious problem
in many districts of West Bengal. The prime concern of delineation of flood-prone
areas is to regulate the land use in the flood-prone areas to restrict damage
potential and also mitigate the negative effects of floods on people and the
economy. In a regulated way, flood-prone areas are required to be developed.
Because, on one hand, it is to be ensured that existing hazard and flood damage
potential do not increase and new developmental works become a step towards
mitigation of disaster risk. In a perspective view, the demarcation and
identification of flood-prone areas of different magnitudes, frequencies and
return periods on a large-scale map seem to have great importance. Satellite
derived flood maps from 2007 to 2016 have been applied to form a flood frequency
map and the same as a group of flood depth maps has been employed to produce the
Flood Damage Map for depth data of flood. Finally, the modelling of flood hazards
has been directed by envisaging amalgamation of Flood Depth and Flood Affected
Frequency. Then the final flood hazard map amalgamated with population and
housing data has been used to ascertain the flood disclosure for these two
components. Flood hazard analysis in the study area revealed that 24% of the
population has been located in high flood hazard zones, where 39% of human
settlements are located in different flood hazard zones.
PMID- 29955271
TI - Urban fire risk control: House design, upgrading and replanning.
AB - Urbanisation leads to house densification, a phenomenon experienced in both
planned and unplanned settlements in cities in developing countries. Such
densification limits fire brigade access into settlements, thereby aggravating
fire disaster risks. In this article, we assess the fire exposure and risks in
residences in informal areas of Mchikichini ward, in Dar es Salaam City,
Tanzania. We rely on interviews of residents and government officials to obtain
background on the occurrence and causes of fire accidents, policy provisions and
regulations, and experiences with fire outbreaks and coping strategies, as well
as on observations and measurements of house transformations, spatial quality and
indoor real life. Our findings suggest that fire risks arise from both
inappropriate structural characteristics and unsound behavioural practices. This
includes unsafe electric practices by residents, poor capacity of residents to
fight fires once started, limited access to structures by firefighting equipment
because of flouting of planning regulations and inadequate awareness of local
government leaders of the magnitude of fire risks. Potential changes to reduce
fire risks in the settlement include the installation of firefighting systems,
restriction of cooking to designated spaces, use of safer cooking energy sources
and lighting means, improvements of vehicle access routes to neighbourhoods,
capacity building at the grass root level and the establishment of community
based fire risk management.
PMID- 29955272
TI - Traditional ecological knowledge and flood risk management: A preliminary case
study of the Rwenzori.
AB - The shift from flood protection to flood risk management, together with recent
arguments on incorporating culture in managing risk, underscores the application
of traditional ecological knowledge (TEK) in managing disasters from flood
hazards. Yet, documentation and incorporation of TEK into practice remains a
challenge. This article contributes to addressing this challenge by exploring the
existence of TEK to flooding in the Rwenzori Mountains, Uganda. Using semi
structured interviews, data were collected from residents of the Nyamwamba
watershed where intense flash floods caused deadly impacts in May 2013. Collected
data were analysed using content, thematic and interpretive analysis techniques.
Results indicate that TEK is exhibited through various traditional ecological
approaches (TEAs). Although endangered, TEAs (conducted through collective action
for a communally accepted end) are framed in three main activities: (1)
assessment and prediction of rainfall and flood by the traditional hydro
meteorologist (diviner) and the traditional rain forecaster (rainmaker); (2) the
mountain cleansing ritual (which act as flood risk awareness platform); and (3)
immunising riverine communities through planting certain indigenous plants, which
improve hydrological systems through their high conservation value for native
ecological diversity. As most TEAs are conducted through collective action, they
represent a platform to understand local capacities and enhance adoption of
measures, and/or a source of knowledge for new measures to address flood risk.
Therefore, full-scale investigations of these TEAs, determining how relevant TEAs
are fine-tuned, and (scientific) measures enculturated based on fine-tuned TEAs
could result in effective flood risk management in various flood hotspots where
TEAs influence action.
PMID- 29955274
TI - An analysis of physical vulnerability to flash floods in the small mountainous
watershed of Aceh Besar Regency, Aceh province, Indonesia.
AB - Vulnerability is a loss rate perceived from elements at risk owing to the impact
of hazards on determined magnitude and frequency. Vulnerability assessment of
elements at risk is a critical component in the risk assessment framework.
Considerable studies regarding flash floods have been conducted, but the depth of
information on vulnerability is still limited. This study presents a model of the
physical vulnerability of buildings caused by the incidence of flash floods,
which is strengthened through intensity of the impact process and loss. This
model used a non-linear regression approach using behavioural data in the form of
the propagation height of the flood. The order-2 polynomial distribution can
represent the relationship between the magnitudes of the best process and loss
rate. The results are the risk assessments of an exposed area in mitigation
strategies.
PMID- 29955273
TI - Managing flood disasters on the built environment in the rural communities of
Zimbabwe: Lessons learnt.
AB - This article is about managing flood disasters affecting the built environment in
the rural communities of Zimbabwe. Using Tsholotsho district in Matabeleland
North province as a case study, the authors argue that flooding has adversely
impacted the built environment through destroying infrastructure. The principal
objectives of this study were to establish the impact of flood disasters on the
built environment, to demarcate factors that perpetuate communities'
vulnerabilities to flooding and to delineate challenges that negate the
management of flood disasters in the built environment. This qualitative study
was based on a purposive sample of 40 participants. Data were collected through
semi-structured interviews and observation methods. The findings were that floods
can damage human shelter, roads, bridges and dams. Locating homesteads near
rivers and dams, using poor-quality construction materials, and lack of flood
warning were found to perpetuate vulnerability to flooding. Poverty and costs of
rebuilding infrastructure, lack of cooperation between the communities and duty
bearers, and failure to use indigenous knowledge were found to be impeding the
management of flood disasters. The study concluded that flood disasters can wipe
out community development gains accumulated over many years. Further, community
vulnerability to flooding in the built environment is socially constructed. The
study posits that addressing the root causes, reducing flood vulnerability and
avoiding risk creation are viable options to development in the built
environment. Lastly, reconstruction following flood disasters is arduous and
gruelling, and not an easy exercise.
PMID- 29955275
TI - Improving disaster risk reduction capacity of District Civil Protection Units in
managing veld fires: A case of Mangwe District in Matabeleland South Province,
Zimbabwe.
AB - This article analysed disaster risk reduction capacity of District Civil
Protection Units (DCPUs) in managing veld fires in Mangwe District of
Matabeleland South Province, Zimbabwe. Veld fires have resulted in unnecessary
material, environmental and economic losses. Communities' livelihoods and
property have been destroyed, and the natural environment depleted. The research
sought to improve disaster risk reduction capacity of DCPUs in managing veld
fires, through new intervention strategies and a new model. The objectives of the
study were to investigate the main causes of veld fires; to analyse their
impacts; to examine the effectiveness of the current intervention strategies; and
to identify challenges in implementing these interventions. Furthermore, the
study sought to recommend new possible intervention strategies. This mainly
qualitative study employed self-administered questionnaires, interviews and focus
group discussions. Questionnaires were used to investigate members of the DCPU's
ideas, views and experiences, interviews solicited perceptions of community
leaders and their subjects, whilst focus-group discussions assisted with
information from members of the District Civil Protection Planning Committee.
Veld fires in the district are mainly caused by human activities, and they are
prevalent during the months of September and October. They affect livelihoods and
the natural environment the most. This study found that DCPUs are not prepared to
manage veld fires and therefore recommended new strategies and adoption of the
community-based disaster risk reduction model. The new strategies include
involving community leaders and members of the communities in DCPUs; regular
training and workshops to members of DCPUs on veld fire management; creation of
fire protection associations; regular campaigns and rehearsal of emergency drills
by the DCPU personnel; the introduction of competitions and incentives in veld
fire management; vigorous public education on the erection of proper fireguards
around homes, cattle pens, crop fields and vegetable gardens; and the imposition
of stiffer penalties for carelessly or deliberately causing veld fires. Policy
makers, governments and stakeholders would benefit from the new intervention
strategies. The community-based disaster risk reduction model would benefit
researchers and disaster risk reduction practitioners.
PMID- 29955276
TI - A call to establish a child-centred disaster management framework in Zimbabwe.
AB - Disasters have increased in intensity and frequency in recent times. However,
disasters do not affect all groups in a society in a similar manner. This
article, based mainly on qualitative desk research and document analysis, aims to
illuminate the specific vulnerability of children to hazards and disasters. The
research showed that owing to their special physiological, psychological,
emotional and economic stature, children are an inherently vulnerable group. The
paper advocates for existing disaster management structures and systems in
Zimbabwe to elevate reduction of disaster risk amongst children within the scope
of child protection, which aims to create a protective environment that shelters
children from any form of harm or abuse. The paper proffers recommendations on
how to design disaster management programmes in Zimbabwe with the needs of
children in mind.
PMID- 29955277
TI - Knowledge apartheid in disaster risk management discourse: Is marrying indigenous
and scientific knowledge the missing link?
AB - Indigenous knowledge (IK) is a key component of disaster risk management (DRM)
and development planning, yet it is often overlooked, with practitioners
preferring to use scientific knowledge. Critics of IK have termed it archaic,
primitive, a constraint to development and inferior to scientific knowledge,
which has contributed to its widespread marginalisation. However, smallholder
farmers in rural Zimbabwe have utilised IK for generations, especially in
predicting rainfall patterns and managing drought conditions, showing that IK can
be a useful tool in DRM. This article presents findings from research on drought
vulnerability and coping conducted in Zimbabwe's Buhera and Chikomba districts in
2009, particularly relating to utilisation of IK in smallholder farming
communities, and argues that unless IK is documented and preserved, its
marginalisation will persist. The research followed a mixed-methods approach
whereby both quantitative and qualitative data were collected and analysed.
Whilst smallholder respondents were randomly selected for household surveys,
snowball sampling was employed for key informant interviews. Respondents
indicated that they utilised some indigenous rainfall pattern predictions gained
from observing and interpreting plant and animal behaviour. Some cultural
practices that were critical to development and utilisation of certain IK were
also threatened with extinction. The article argues for 'marrying' IK and
scientific knowledge, in the hope that the two will offset each other's
weaknesses, resulting in some kind of hybrid knowledge that will be critical for
promoting sustainable agricultural production in Zimbabwe. However, this is not
for disregard the challenges associated with knowledge hybridisation, as these
two types of knowledge are grounded on differing foundations.
PMID- 29955278
TI - Modelling social vulnerability in sub-Saharan West Africa using a geographical
information system.
AB - In recent times, disasters and risk management have gained significant attention,
especially with increasing awareness of the risks and increasing impact of
natural and other hazards especially in the developing world. Vulnerability, the
potential for loss of life or property from disaster, has biophysical or social
dimensions. Social vulnerability relates to societal attributes which has
negative impacts on disaster outcomes. This study sought to develop a spatially
explicit index of social vulnerability, thus addressing the dearth of research in
this area in sub-Saharan Africa. Nineteen variables were identified covering
various aspects. Descriptive analysis of these variables revealed high
heterogeneity across the South West region of Nigeria for both the state and the
local government areas (LGAs). Feature identification using correlation analysis
identified six important variables. Factor analysis identified two dimensions,
namely accessibility and socioeconomic conditions, from this subset. A social
vulnerability index (SoVI) showed that Ondo and Ekiti have more vulnerable LGAs
than other states in the region. About 50% of the LGAs in Osun and Ogun have a
relatively low social vulnerability. Distribution of the SoVI shows that there
are great differences within states as well as across regions. Scores of
population density, disability and poverty have a high margin of error in
relation to mean state scores. The study showed that with a geographical
information system there are opportunities to model social vulnerability and
monitor its evolution and dynamics across the continent.
PMID- 29955279
TI - Artisanal small-scale mining: Potential ecological disaster in Mzingwane
District, Zimbabwe.
AB - Artisanal small-scale mining (ASM) has devastating impacts on the environment,
such as deforestation, over-stripping of overburden, burning of bushes and use of
harmful chemicals like mercury. These environmental impacts are a result of
destructive mining, wasteful mineral extraction and processing practices and
techniques used by the artisanal small-scale miners. This paper explores the
ecological problems caused by ASM in Mzingwane District, Zimbabwe. It seeks to
determine the nature and extent to which the environment has been damaged by the
ASM from a community perspective. Interviews, questionnaires and observations
were used to collect qualitative data. Results indicated that the nature of the
mining activities undertaken by unskilled and under-equipped gold panners in
Mzingwane District is characterised by massive stripping of overburden and
burning of bushes, leading to destruction of large tracts of land and river
systems and general ecosystem disturbance. The research concluded that ASM in
Mzingwane District is an ecological time bomb, stressing the need for appropriate
modifications of the legal and institutional frameworks for promoting sustainable
use of natural resources and mining development in Zimbabwe. Government, through
the Ministry of Small Scale and Medium Enterprises, need to regularise and
formalise all gold mining activities through licensing, giving permanent claims
and operating permits to panners in order to recoup some of the added costs in
the form of taxes. At the local level, the Mzingwane Rural District Council
(MRDC) together with the Environmental Management Agency (EMA) need to design
appropriate environmental education and awareness programmes targeting the local
community and gold panners.
PMID- 29955280
TI - Identifying hydro-meteorological events from precipitation extremes indices and
other sources over northern Namibia, Cuvelai Basin.
AB - Worldwide, more than 40% of all natural hazards and about half of all deaths are
the result of flood disasters. In northern Namibia flood disasters have increased
dramatically over the past half-century, along with associated economic losses
and fatalities. There is a growing concern to identify these extreme
precipitation events that result in many hydro-meteorological disasters. This
study presents an up to date and broad analysis of the trends of hydro
meteorological events using extreme daily precipitation indices, daily
precipitation data from the Grootfontein rainfall station (1917-present),
regionally averaged climatologies from the gauged gridded Climate Research Unit
(CRU) product, archived disasters by global disaster databases, published
disaster events in literature as well as events listed by Mendelsohn, Jarvis and
Robertson (2013) for the data-sparse Cuvelai river basin (CRB). The listed events
that have many missing data gaps were used to reference and validate results
obtained from other sources in this study. A suite of ten climate change extreme
precipitation indices derived from daily precipitation data (Grootfontein
rainfall station), were calculated and analysed. The results in this study
highlighted years that had major hydro-meteorological events during periods where
no data are available. Furthermore, the results underlined decrease in both the
annual precipitation as well as the annual total wet days of precipitation,
whilst it found increases in the longest annual dry spell indicating more extreme
dry seasons. These findings can help to improve flood risk management policies by
providing timely information on historic hydro-meteorological hazard events that
are essential for early warning and forecasting.
PMID- 29955281
TI - When nature frowns: A comprehensive impact assessment of the 2012 Babessi floods
on people's livelihoods in rural Cameroon.
AB - Floods are the most common natural disasters worldwide. Much of the growing
literature on the impact of floods, especially in developed countries, and to a
lesser extent in rural areas of developing countries, concentrates on economic
rather than a comprehensive assessment of combined effects on people's
livelihoods. Holistic floods impact assessments are often done long after the
shock, raising problems of data reliability following long recall periods,
although post-disaster needs assessments when carried out earlier can facilitate
appropriate disaster recovery, relief and reconstruction activities. We applied
the sustainable livelihoods framework as a comprehensive approach to assess the
impacts of the Babessi floods in 2012 on livelihoods in rural (north western
region) of Cameroon 6 weeks after the floods. Using a structured questionnaire,
data was collected from victims before and after the floods, using recall
methods. A matched sample of nonvictims randomly selected from the same village
as the victims was used to assess vulnerability to the floods by household type.
Floods were found to have serious economic, social, human and food security
impacts on victims. Both government and nongovernmental support were jointly
crucial for household recovery. Comparatively observed high levels of recovery
were attributed to the low loss of human lives. The article concludes with the
need for comprehensive approaches to floods impact assessments. The need for
combining formal and informal instruments in post-disaster management in rural
areas is also emphasised.
PMID- 29955282
TI - Vulnerability assessments, identity and spatial scale challenges in disaster-risk
reduction.
AB - Current approaches to vulnerability assessment for disaster-risk reduction (DRR)
commonly apply generalised, a priori determinants of vulnerability to particular
hazards in particular places. Although they may allow for policy-level legibility
at high levels of spatial scale, these approaches suffer from attribution
problems that become more acute as the level of analysis is localised and the
population under investigation experiences greater vulnerability. In this
article, we locate the source of this problem in a spatial scale mismatch between
the essentialist framings of identity behind these generalised determinants of
vulnerability and the intersectional, situational character of identity in the
places where DRR interventions are designed and implemented. Using the
Livelihoods as Intimate Government (LIG) approach to identify and understand
different vulnerabilities to flooding in a community in southern Zambia, we
empirically demonstrate how essentialist framings of identity produce this
mismatch. Further, we illustrate a means of operationalising intersectional,
situational framings of identity to achieve greater and more productive
understandings of hazard vulnerability than available through the application of
general determinants of vulnerability to specific places and cases.
PMID- 29955283
TI - Environmental challenges posed by veld fires in fragile regions: The case of the
Bulilima and Mangwe districts in southern Zimbabwe.
AB - This original research confronted challenges to environmental management and
sustainability posed by veld fires in the Bulilima and Mangwe Districts of
Matabeleland in the South Province in southern Zimbabwe. Veld fires have affected
the fauna and flora, polluted air and water, and destroyed livelihoods. The study
aimed at establishing challenges to environmental sustainability posed by veld
fires, identifying the type of environment upon which veld fires have impacted,
analysing legal issues and other interventions surrounding the control of veld
fires and suggesting new control measures for veld fires. A qualitative research
design and quota sampling were used. The study involved 30 participants. Data was
collected through a questionnaire, an interview guide and participant
observation. Challenges to environmental management and sustainability posed by
veld fires include property damage, reduced soil fertility, destruction of
vegetation, air and water pollution and destruction of wildlife. Most veld fires
are a result of human actions that emanate from the disposal of cigarettes, the
burning of vegetation when preparing fields, the use of fire by hunters, smoking
out bees and the making of fires by motorists along highways. The government
should consider reviewing the current environmental statues. Fireguards should be
wide enough to lessen veld-fire impact. Lastly, veld-fire campaigns and
rehearsals should be run on a regular basis. It is hoped that this work would
make a significant contribution through improving the current thinking about
environmental management and sustainability, thereby benefiting policy makers,
practitioners and stakeholders.
PMID- 29955284
TI - Modelling non-stationary annual maximum flood heights in the lower Limpopo River
basin of Mozambique.
AB - In this article we fit a time-dependent generalised extreme value (GEV)
distribution to annual maximum flood heights at three sites: Chokwe, Sicacate and
Combomune in the lower Limpopo River basin of Mozambique. A GEV distribution is
fitted to six annual maximum time series models at each site, namely: annual
daily maximum (AM1), annual 2-day maximum (AM2), annual 5-day maximum (AM5),
annual 7-day maximum (AM7), annual 10-day maximum (AM10) and annual 30-day
maximum (AM30). Non-stationary time-dependent GEV models with a linear trend in
location and scale parameters are considered in this study. The results show lack
of sufficient evidence to indicate a linear trend in the location parameter at
all three sites. On the other hand, the findings in this study reveal strong
evidence of the existence of a linear trend in the scale parameter at Combomune
and Sicacate, whilst the scale parameter had no significant linear trend at
Chokwe. Further investigation in this study also reveals that the location
parameter at Sicacate can be modelled by a nonlinear quadratic trend; however,
the complexity of the overall model is not worthwhile in fit over a time
homogeneous model. This study shows the importance of extending the time
homogeneous GEV model to incorporate climate change factors such as trend in the
lower Limpopo River basin, particularly in this era of global warming and a
changing climate.
PMID- 29955285
TI - A review of studies on community based early warning systems.
AB - Community-based early warning systems involve community driven collection and
analysis of information that enable warning messages to help a community to react
to a hazard and reduce the resulting loss or harm. Most early warning systems are
designed at the national or global level. Local communities' capacity to predict
weather conditions using indigenous knowledge has been demonstrated in studies
focusing on climate change and agriculture in some African countries. This review
was motivated by successes made in non-disease specific community-based early
warning systems with a view to identify opportunities for developing similar
systems for malaria. This article reviewed the existing community-based early
warning systems documented in literature. The types of disasters that are
addressed by these systems and the methodologies utilised in the development of
the systems were identified. The review showed that most of the documented
community-based early warning systems focus on natural disasters such as floods,
drought, and landslides. Community-based early warning systems for human diseases
are very few, even though such systems exist at national and regional and global
levels. There is a clear gap in terms of community-based malaria early warning
systems. The methodologies for the development of the community-based early
warning systems reviewed mainly derive from the four elements of early warning
systems; namely risk knowledge, monitoring, warning communication and response
capability. The review indicated the need for the development of community based
early warning systems for human diseases.
PMID- 29955286
TI - The Port Alfred floods of 17-23 October 2012: A case of disaster (mis)management?
AB - An intense cut-off low weather system, more commonly known regionally as a 'black
south-easter', caused severe flooding in Port Alfred and the surrounding coastal
areas from 17 to 23 October 2012. Unconfirmed reports of up to 700 mm of rainfall
for the period were recorded. Damage caused by the flooding was estimated at R500
million. Eight deaths were recorded. The poorly maintained and ageing
infrastructure and storm water systems could not withstand the floodwaters, and
as a result, damage was worse than it should have been. Many houses, particularly
in the surrounding townships and informal settlements, were destroyed. Disease
threats arose, including cholera, diarrhoea and influenza. The South African
Weather Service issued weather warnings of severe local flooding in the coastal
areas of the Eastern Cape a few days before the flood event. Unfortunately, there
was a delay in communicating the severe weather warning effectively to the
public, relevant authorities and role-players by local disaster management
officials. In addition, there was poor and ineffective local coordination of
disaster response and relief efforts. This paper examines the 2012 flood event
from both meteorological and disaster management perspectives, using a combined
qualitative and quantitative research approach. Findings point to a critical lack
of coordination amongst the various role-players before, during and after the
disaster. Recommendations for improved proactive and coordinated disaster risk
management and disaster risk reduction for the region are made.
PMID- 29955287
TI - Public health policy in a time of change and disaster in South Africa: 1910-1920.
AB - With the establishment of the Union of South Africa in 1910, the central focus of
the newly appointed government was to alter and consolidate the policies of the
pre-Union colonies that differed materially in many respects and to substitute
them with uniform policies that had to be implemented as a consolidated whole for
the Union. This central focus was applied to a number of policies, notably those
for the black people, immigration, education, labour, national defence and the
development and implementation of railway, mining and agricultural policies.
However, an omission occurred with regard to the consideration of a comprehensive
public health policy by the political parties and the Union Parliament,
consisting of white people only. This article examines this omission during the
first 10 years of the Union of South Africa (1910-1920), during the three 5
yearly general elections (on 15 September 1910, 20 October 1915 and 10 March
1920), and argues that this lack of consideration of a comprehensive public
health policy can be found in the theory of party political responsible
government during unification, which was further developed by Kavanagh, that
party political manifestos act as the guiding force behind the policy matters
that are discussed and decided upon in Parliament. The article confirms that the
reason for not establishing a comprehensive public health policy prior to the
outbreak of the influenza epidemic in 1918 was the incidental and piecemeal
fashion in which expressions on public health appeared in the published party
political manifestos, which in turn influenced the proceedings of Parliament.
This political negligence was, however, quickly overturned by Parliament
immediately after the epidemic, showing the influence of this demographic
disaster on political thinking and action.
PMID- 29955288
TI - Modelling a critical infrastructure-driven spatial database for proactive
disaster management: A developing country context.
AB - The understanding and institutionalisation of the seamless link between urban
critical infrastructure and disaster management has greatly helped the developed
world to establish effective disaster management processes. However, this link is
conspicuously missing in developing countries, where disaster management has been
more reactive than proactive. The consequence of this is typified in poor
response time and uncoordinated ways in which disasters and emergency situations
are handled. As is the case with many Nigerian cities, the challenges of urban
development in the city of Abeokuta have limited the effectiveness of disaster
and emergency first responders and managers. Using geospatial techniques, the
study attempted to design and deploy a spatial database running a web-based
information system to track the characteristics and distribution of critical
infrastructure for effective use during disaster and emergencies, with the
purpose of proactively improving disaster and emergency management processes in
Abeokuta.
PMID- 29955289
TI - Expanding the disaster risk management framework: Measuring the constructed level
of national identity as a factor of political risk.
AB - Political risk is identified as a dominant risk category of disaster risk
management (DRM) which could negatively affect the success of those measures
implemented to reduce disaster risk. Key to political risk is the construct of
national identity which, if poorly constructed, could greatly contribute to
political risk. This article proposed a tool to measure the construct of national
identity and to provide recommendations to strengthen the construct in order to
mitigate the exacerbating influence it may have on political risk and ultimately
on DRM. The design of the measurement tool consisted of a mixed methodological
approach employing both quantitative and qualitative data. The data collection
instruments included a literature review (which is shortly provided in the
previous sections) and an empirical study that utilised data obtained through
structured questionnaires. Although the results of the proposed measuring
instrument did not include a representative sample of all the cultures in South
Africa, the results alluded to different levels for the construction of national
identity among black and white respondents, possibly because of different
ideological expectations among these groups. The results of the study should be
considered as a validation of the measuring tool and not necessarily of the
construct of national identity in South Africa. The measuring tool is thus
promising for future studies to reduce political risk and ultimately disaster
risk.
PMID- 29955290
TI - Onshore preparedness for hazardous chemical marine vessel accidents: A case
study.
AB - Hazardous and noxious substances (HNS) are widely transported in marine vessels
to reach every part of the world. Bulk transportation of hazardous chemicals is
carried out in tank container-carrying cargo ships or in designed vessels.
Ensuring the safety of HNS containers during maritime transportation is
critically important as the accidental release of any substance may be lethal to
the on-board crew and marine environment. A general assumption in maritime
accidents in open ocean is that it will not create any danger to the coastal
population. The case study discussed in this article throws light on the dangers
latent in maritime HNS accidents. An accident involving an HNS-carrying marine
vessel in the Arabian Sea near the coast of Yemen became a safety issue to the
coastal people of Kasargod District of Kerala, India. The ship carried more than
4000 containers, which were lost to the sea in the accident. Six HNS tank
containers were carried by the waves and shored at the populated coast of
Kasargod, more than 650 nautical miles east from the accident spot. The
unanticipated sighting of tank containers in the coast and the response of the
administration to the incident, the hurdles faced by the district administration
in handling the case, the need for engaging national agencies and lessons learned
from the incident are discussed in the article. This case study has proven that
accidents in the open ocean have the potential to put the coastal areas at risk
if the on-board cargo contains hazardous chemicals. Littoral nations, especially
those close to the international waterlines, must include hazardous chemical
spills to their oil spill contingency plans.
PMID- 29955291
TI - Inadequate stakeholder management and its effect on a coherent sinkhole risk
management strategy: The case of the Merafong Local Municipality, South Africa.
AB - The Merafong Local Municipality (MLM) has historically suffered financial and
human losses because of the presence of dolomite and the consequent formation of
sinkholes. There is a great need for the MLM to address the risk posed by
sinkholes to ensure the continued safety of communities. However, as the risk is
so pervasive, the MLM needs to coordinate their risk reduction strategies with a
wide array of stakeholders in the municipality. Efficient stakeholder management
is thus crucial if the sinkhole risk is to be addressed appropriately. This
article reviews the current status of stakeholder management in the MLM as it
pertains to the formulation of a holistic sinkhole risk reduction strategy.
Findings indicate that there are serious deficiencies in the MLM's stakeholder
management relating to key risk management processes such as community
involvement in risk management structures, disaster risk assessment, training and
awareness, and early warning and response. Improved stakeholder management could
be characterised by the following factors: improved two-way communication between
the municipality and community stakeholders, fostering a relationship based upon
trust and equality amongst stakeholders, participation by a wide array of
stakeholder groups affected by the sinkhole risk and a mutual commitment by all
stakeholders to address the risk. These factors could contribute to enhancing
current and future sinkhole risk reduction strategies.
PMID- 29955292
TI - A review of children's participation in disaster risk reduction.
AB - Children are often excluded from disaster risk reduction (DRR) activities, yet
they are one of the most vulnerable groups to disasters. As a result, they
experience physical, psychological and educational vulnerabilities. There is lack
of research on children's participation in DRR and their potential value in
strengthening community resilience has been largely overlooked. Therefore, this
article highlights the existing research and knowledge gap in children's
participation in DRR. It highlights the existing research and knowledge gap by
reviewing literature on the concept of children's participation in DRR. The
article analyses the different ways in which children's participation in DRR has
been conceptualised, and how this has influenced the way children are involved in
DRR. The study will then explore the obstacles to involving children and their
potential contribution in DRR.
PMID- 29955293
TI - Perception-based analysis of climate change effect on forest-based livelihood:
The case of Vhembe District in South Africa.
AB - Forests are vulnerable to climate change and are also major sources of livelihood
for many rural households in Africa. This study examines rural people's
perceptions of climate change impacts on forest-based livelihoods using rural
communities of Vhembe District in South Africa as a case study. The study was
based on the principles of perceived impact-based assessment, and sustainable
livelihoods framework. Using the stratified proportionate random sampling
procedure in combination with weighted Enumeration Area for the selected
communities, 366 households were chosen and interviewed. Data analysis involved
computing frequencies and conducting the Chi-square, binomial tests and binary
logistic regression analysis. The respondents identified erratic rainfall,
extreme temperature, extreme drought and flooding as key climatic events in their
community. But not all identified key climatic events were perceived to
constitute risk to forest products and forest-based livelihood. Only extreme
drought was indicated to constitute risk to availability of forest products. In
addition, the binary logistic regression showed a significant difference (p <
0.05) in the perceived risk of climate change to the availability of essential
forest products across the three municipalities. Hence the need for forest
development initiatives that target vulnerable forest products per community as a
means of enhancing resilience of forest-based livelihood to climate change
impacts in rural community development in South Africa.
PMID- 29955294
TI - Indigenous knowledge for disaster risk reduction: An African perspective.
AB - Indigenous knowledge is valuable knowledge that has helped local communities all
over the world survive for generations. This knowledge originates from the
interaction between members of the community and the environment in which they
live. Although much has been written about indigenous knowledge, its
documentation in the area of disaster risk reduction and climate change in Africa
has been very limited. The wealth of this knowledge has not been well-recognised
in the disaster risk reduction field, as policy-makers still rely on mitigation
strategies based on scientific knowledge. Colonialism and lack of proper
documentation of indigenous knowledge are some of the contributing factors to
this. Ignoring the importance of understanding adaptive strategies of the local
people has led to failed projects. Understanding how local people in Africa have
managed to survive and adapt for generations, before the arrival of Western
education, may be the key to developing sustainable policies to mitigate future
challenges. Literature used in this article, obtained from the books, papers and
publications of various experts in the fields of disaster risk reduction, climate
change, indigenous knowledge and adaptation, highlight the need for more interest
to be shown in indigenous knowledge, especially in the developing country
context. This would lead to better strategies which originate from the community
level but would aim for overall sustainable development in Africa.
PMID- 29955295
TI - Coastal erosion management in Accra: Combining local knowledge and empirical
research.
AB - Coastal erosion along the Accra coast has become a chronic phenomenon that
threatens both life and property. The issue has assumed a centre stage of
national debate in recent times because of its impact on the coastal communities.
Lack of reliable geospatial data hinders effective scientific investigations into
the changing trends in the shoreline position. However, knowledge about coastal
erosion, by the local people, and how far the shoreline has migrated inland over
time is high in the coastal communities in Accra. This opens a new chapter in
coastal erosion research to include local knowledge of the local settlers in
developing sustainable coastal management. This article adopted a scientific
approach to estimate rate of erosion and tested the results against perceived
erosion trend by the local settlers. The study used a 1974 digital topographic
map and 1996 aerial photographs. The end point rate statistical method in DSAS
was used to compute the rates of change. The short-term rate of change for the 22
year period under study was estimated as -0.91 m/annum +/- 0.49 m/annum. It was
revealed that about 79% of the shoreline is eroding, while the remaining 21% is
either stabilised or accreting. It emerged, from semi-structured interviews with
inhabitants in the Accra coastal communities, that an average of about 30 m of
coastal lands are perceived to have been lost to erosion for a period of about 20
years. This translates to a historic rate of change of about 1.5 m/year, which
corroborates the results of the scientific study. Again this study has
established that the local knowledge of the inhabitants, about coastal erosion,
can serve as reliable information under scarcity of scientific data for coastal
erosion analyses in developing countries.
PMID- 29955296
TI - Public and private partnership in disaster risk management.
AB - Private and public partnerships are defended by both guidelines for action and
legal frameworks for disaster risk management. The objective of this study is to
identify a framework for action that allows joint collaborative partnership
between these sectors. The theoretical discussion brings concepts that raise
questions that permeate the possibility of partnership based on the new Sendai
framework, as well as corporate social responsibility in the value, balance and
accountability (VBA) integrative model. The presented framework is compared to
the experience of the tornado which occurred in Brazil in the city of Xanxere
(Santa Catarina) in 2015. We came to the conclusion that partnership advance
results from paradigm shifts in both sectors, on the one hand, with the
development of management mechanisms that clearly define roles and
responsibilities of those involved, and, on the other hand, motivation for
responsible business conduct.
PMID- 29955297
TI - Application of Standardized Precipitation Index to assess meteorological drought
in Bangladesh.
AB - Bangladesh is one of the vulnerable countries of the world for natural disasters.
Drought is one of the common and severe calamities in Bangladesh that causes
immense suffering to people in various ways. The present research has been
carried out to examine the frequency of meteorological droughts in Bangladesh
using the long-term rainfall data of 30 meteorological observatories covering the
period of 1948-2011. The study uses the highly effective Standardized
Precipitation Index (SPI) for drought assessment in Bangladesh. By assessing the
meteorological droughts and the history of meteorological droughts of Bangladesh,
the spatial distributions of meteorological drought indices were also analysed.
The spatial and temporal changes in meteorological drought and changes in
different years based on different SPI month intervals were analysed. The results
indicate that droughts were a normal and recurrent feature and it occurred more
or less all over the country in virtually all climatic regions of the country. As
meteorological drought depends on only rainfall received in an area, anomaly of
rainfall is the main cause of drought. Bangladesh experienced drought in the
years 1950, 1951, 1953, 1954, 1957, 1958, 1960, 1961, 1962, 1963, 1965, 1966,
1967 and 1971 before independence and after independence Bangladesh has
experienced droughts in the years 1972, 1973, 1975, 1979, 1980, 1983, 1985, 1992,
1994, 1995, 2002, 2004, 2006, 2009 and 2011 during the period 1948-2011. The
study indicated that Rajshahi and its surroundings, in the northern regions and
Jessore and its surroundings areas, the island Bhola and surrounding regions, in
the south-west region, were vulnerable. In the Sylhet division, except Srimongal,
the areas were not vulnerable but the eastern southern sides of the districts
Chittagong, Rangamati, Khagrachhari, Bandarban and Teknaf were vulnerable. In the
central regions, the districts of Mymensingh and Faridpur were more vulnerable
than other districts.
PMID- 29955298
TI - Insurance mechanisms for tropical cyclones and droughts in Pacific Small Island
Developing States.
AB - One group of locations significantly affected by climate-related losses and
damage is the Small Island Developing States (SIDS). One mechanism aiming to
reduce such adverse impacts is insurance, with a wide variety of products and
models available. Insurance for climate-related hazards affecting Pacific SIDS
has not been investigated in detail. This article contributes to filling this gap
by exploring how insurance mechanisms might be implemented in the Pacific SIDS
for tropical cyclones and droughts. The study examines opportunities and
constraints or limitations of some existing insurance mechanisms and programmes
as applied to the Pacific SIDS. Eight insurance mechanisms are compared and
discussed regarding the premium cost compared to the gross domestic product per
capita, the amount of payout compared to the damage cost, the reserve and
reinsurance, and the disaster risk reduction incentives. As such, this article
offers a decision-making tool on insurance development for the Pacific SIDS.
Ultimately, implementing disaster insurance for the Pacific SIDS depends on
political will and external technical and financial assistance.
PMID- 29955299
TI - Developing a community-centred malaria early warning system based on indigenous
knowledge: Gwanda District, Zimbabwe.
AB - Malaria continues to be a major public health problem in Sub-Saharan Africa
despite efforts that have been made to prevent and control the disease for many
decades. The knowledge on prediction and occurrence of the disease that
communities acquired over the years has not been seriously considered in control
programmes. This article reports on studies that aimed to integrate indigenous
knowledge systems (IKS) on malaria into the malaria control programme in Gwanda
District, Zimbabwe. The studies were conducted over a 3-year period. Data were
collected using participatory rural appraisals, key informant interviews,
household interviews and workshops in three wards (11, 15 and 18) with the
highest malaria incidence in Gwanda District. Disease livelihoods calendars
produced by the community showed their knowledge on the relationship between
malaria, temperature and rainfall, and thus an understanding of malaria as a
hazard. Volunteer IKS experts willing to record the indigenous environmental
indicators for the occurrence of malaria in the study area were identified by the
communities. Indigenous environmental indicators for the occurrence of malaria
were classified as insects, plant phenology, animals, weather and cosmological
indicators. Plant phenology was emphasised more than the other indicators. A
community-based malaria early warning system model was developed using the
identified IKS indicators in two of the wards using the ward health team as an
entry point to the health system. In the model, data on indicators were collected
at the village level by IKS experts, analysed at ward level by IKS experts and
health workers and relayed to the district health team.
PMID- 29955300
TI - Indigenous practices of environmental sustainability in the Tonga community of
southern Zambia.
AB - Culture plays a significant role in conserving the environment. The purpose of
this study was to explore the measures that have been employed by the Tonga
people of southern Zambia to sustain their local biophysical environment. The
research focussed on investigating the strategies which they use to conserve the
soil, water, animals, medicinal and fruit plants, and rangeland. A qualitative
research design was used in the study. The data were collected through interviews
with elderly Tonga people and herbalists, and through observation and personal
participation in the daily life of the Tongas. The study reveals that selective
harvesting, totemism and taboos, organic farming, crop rotation and
intercropping, sacredness of water sources and traditional authority are the main
instruments of environmental conservation amongst the Tonga. The article
concludes that governments, policymakers and environmentalists need to give the
conservation strategies employed by indigenous people the prominence they deserve
for environmental sustainability.
PMID- 29955301
TI - Assessing the knowledge, attitudes and practices regarding cholera preparedness
and prevention in Ga-Mampuru village, Limpopo, South Africa.
AB - The study assessed the knowledge, attitudes and practices of cholera prevention
and preparedness in Ga-Mampuru village (Limpopo, South Africa). Interviewers
collected data using a two-pronged method, namely a household questionnaire (open
and closed-ended questions) to assess knowledge and attitudes about cholera and
observations to assess practices in the prevention and management of the disease.
Additionally, interviewers took pictures with the respondents' permission. Ninety
six respondents were interviewed. Most respondents (86%) indicated they knew how
cholera was contracted with 84% indicating contaminated water as a source. Ninety
percent of the respondents indicated they knew how to prevent contracting
cholera. All respondents generally knew that cholera could be treated with
medicine received at a health-care facility or worker. Fewer respondents (58%)
had specific knowledge such as the use of rehydration solutions. The respondents'
high level of prevention practices could be biased. Interviewers observed that
many practices were not adhered to, like not washing hands, not using toilet
paper and throwing waste in respondents' yards. Therefore, the community of Ga
Mampuru had not reached a stage of adequate cholera prevention and preparedness
in spite of the fact that they were aware of cholera risks and risk-reduction
measures.
PMID- 29955302
TI - The impact of and responses to flooding in Thulamela Municipality, Limpopo
Province, South Africa.
AB - The frequency of climate-related disasters such as floods is growing due to
environmental and human factors. This paper examines the impact of flooding and
communities' perceptions towards responses to flooding in the cases of Maniini
and Tshilungwi Villages in the Thulamela Municipality in the Limpopo Province of
South Africa. A questionnaire survey was conducted with 60 household respondents
in the two selected villages and then analysed. Key-informant interviews with
community leaders and municipality officials established the key impact of and
responses to the flooding. Secondary data on flooding provided useful historical
trends in the region. Field observations assisted in corroborating information
provided in interviews. The findings indicate that communities are vulnerable to
flood disasters, and these disasters had a significant impact on infrastructure
and the livelihood of the selected communities. An increase in household income
and levels of education as well as access to grants decreased households'
vulnerability in cases of flooding. The responses to flooding by the municipality
were viewed negatively by the community who did not support permanent relocation.
Hence, the article points out the need to strengthen coping mechanisms by local
governments and communities themselves in order to cope with the impact of
flooding.
PMID- 29955303
TI - Flooding and its impacts on Nkondo community in Rundu, Kavango east region of
Namibia, 1950s.
AB - This is a study on flooding and its impact on the Nkondo community in Rundu, in
the Kavango area of Namibia. It draws from archival sources at the National
Archives of Namibia. Whilst archival documents provide an idea of what and how
colonial officials thought of and related to the colonial subjects, they cannot
represent the feelings, beliefs and interpersonal relationships of the ordinary
people. This article thus made use of oral interviewing, not as a means to fill
the gap but as an alternative to exploring memories of former Nkondo residents
about the 1950s flood and its impact. Interviews were carried out in 2004 and
2005 when 14 people were interviewed for the histories of forced removals in
Rundu, but only five are used for this article as they specifically speak to the
story of flooding. Interviewees were chosen through referrals from the headmen of
the surrounding villages of Rundu. Interviewees were asked questions that provide
a chronological representation of a case study of forced relocations in Rundu.
The article is an important historical piece that draws on unique oral-history
regarding flooding and its impact. Furthermore, it is a story about power,
politics and colonial dynamics and forced relocation using flooding as a pretext.
The article indicates how colonial authorities made use of this benevolent excuse
of a natural disaster to compel people to move permanently to new areas so as to
fulfil the colonial administration's political agenda of security and control
over the population. The article indicates that flood-prone communities may fear
relocating permanently due to cultural, social and economic factors. Thus, the
government should not use force to relocate communities but should address
communities' fears and provide them with support in relocated areas.
PMID- 29955304
TI - Post-traumatic stress disorder amongst children aged 8-18 affected by the 2011
northern-Namibia floods.
AB - Extreme flooding in the northern parts of Namibia occurred in 2011, impacting
many school-going children in the region. The rationale for the current research
is to assess post-traumatic stress disorder (PTSD) on school children as a result
of the floods. A self-administered Child Trauma Screening Questionnaire (CTSQ)
with closed-ended questions was administered to 480 children between the ages of
eight and 18 years at their respective schools. The CTSQ consists of five items
assessing re-experiencing and five items assessing hyper-arousal symptoms. The
results show that 55.2% of learners aged 12 and below and 72.8% of learners aged
13 and above reported experiencing symptoms of trauma from the floods 2 years
after the event. These percentages were quite high and are therefore a cause for
concern. Given the magnitude of this problem, it is important for the government
and other stakeholders to provide the necessary psychological and/or emotional
support in the event of future floods or similar disasters.
PMID- 29955305
TI - Some international perspectives on legislation for the management of human
induced safety risks.
AB - Legislation that governs the health and safety of communities near major-hazard
installations in South Africa is largely based on existing legislation that had
been developed in the United Kingdom and other European Union countries. The
latter was developed as a consequence of several major human-induced
technological disasters in Europe. The history of the evolution of health-and
safety legislation for the protection of vulnerable communities in European Union
(EU) countries, France, Malaysia and the USA is explored through a literature
survey. A concise comparison is drawn between EU countries, the USA and South
Africa to obtain an exploratory view of whether current South-African legislation
represents an optimum model for the protection of the health-and-safety of
workers and communities near major-hazard installations. The authors come to the
conclusion that South-African legislation needs revision as was done in the UK in
2011. Specific areas in the legislation that need revision are an overlap between
occupational health and safety and environmental legislation, appropriate land
use planning for the protection of communities near major-hazard installations,
the inclusion of vulnerability studies and the refinement of appropriate decision
making instruments such as risk assessment. This article is the first in a series
that forms part of a broader study aimed at the development of an optimised model
for the regulatory management of human-induced health and safety risks associated
with hazardous installations in South Africa.
PMID- 29955306
TI - Combating HIV and/or AIDS: A challenge to Millennium Development Goals for
disaster managers in the Southern African Development Community.
AB - Disaster management is a process of planning and implementation of measures
involving multiple disciplines and sectors; hence Millennium Development Goals
(MDGs) cannot go unnoticed. Approximately 189 member states agreed to endeavour
to achieve MDGs which should be accomplished by 2015. The purpose of this
research was to establish the primary involvement of the disaster management
fraternity within the Southern African Development Community (SADC) region in
this agreement. SADC countries are the countries with a high prevalence of HIV
and AIDS and they feature on the disaster manager's priority list of hazards,
hence the focus on MDG 6 for this study. Various data gathering tools were
employed and included making use of indicators developed by the United Nations to
review disaster management statutes or civil protection statutes and scholarly
documents on the progress of MDG 6. Structured interviews were carried out with
heads of disaster management centres of SADC countries through the guidance of
MDG 6 indicators. The main findings were that most statutes do acknowledge the
fight against epidemics and most disaster managers are aware of MDG 6 and are
involved in its achievement. It was recommended that disaster managers should be
part of the Post 2015 MDG delegation.
PMID- 29955307
TI - Indigenous food security revival strategies at the village level: The gender
factor implications.
AB - This article is based on an evaluation concerning the practice of the Zunde
raMambo concept (commonly referred to as Zunde) in four of Zimbabwe's 52
districts; (Mangwe, Lupane, Guruve and Hwedza). Zunde is a social security system
providing protection against food shortages to vulnerable families and is
coordinated by chiefs. The Zunde concept identifies with Ndebele and Shona rural
communities in Zimbabwe. Thus, this evaluation sought to determine the relevance
and fulfilment of the Zunde project objectives, namely: efficiency,
effectiveness, impact and sustainability. The revived Zunde practice extends a
long way in reducing food insecurity in vulnerable communities. Although the
concept may be as old as the Zimbabwean culture, it had been abandoned as
communities became urbanised. The Chief's Council of Zimbabwe, in collaboration
with the Nutrition Unit of the Ministry of Health and Child Welfare have
rekindled it. However, to revive this indigenous knowledge practice, there is
need to assess the nature of existing social and economic structures, leadership,
gender roles and the availability of resources such as land, inputs and
implements. This article, which is based on both qualitative and quantitative
data, collected between September 2013 and March 2014, goes on to reflect on
policy issues surrounding disaster risk reduction (DRR) and survival strategies
used by vulnerable communities in rural areas of Zimbabwe. It recommends that the
gender factor approach offers the best means possible to understand peoples'
needs and challenges as well as how these can be satisfied and resolved
respectively.
PMID- 29955308
TI - The timing of agricultural production in hazard-prone areas to prevent losses at
peak-risk periods: A case of Malawi, Madagascar and Mozambique.
AB - Hazard-prone areas in southern Africa experience many natural hazards, which
include cyclones, floods and droughts. The severe climatic conditions of southern
Africa have an especially large impact on the agricultural practices of small
scale farmers. These hazards should be mitigated to ensure more resilient
communities and food security. This study mainly focuses on the timing of
agricultural production in hazard-prone areas to prevent losses at peak-risk
periods by adapting the agricultural cycle. This study focuses on the
agricultural activities of small-scale farmers in Malawi, Madagascar and
Mozambique. A literature review is presented, and a mixed-method research design
were followed to determine the timing of production followed by these small-scale
farmers and its impact on production and food security. Although this study found
that the small-scale farmers generally plant with the first rains, it is
recommended by literature that early planting should be practised to ensure
optimal production. It is also recommended that small-scale farmers should
implement water-management techniques for dry periods, and when farmers practice
late planting, the use of residual-moisture retention should be utilised as a
mitigation measure. This will in effect ensure that the communities are less
vulnerable during peak-risk periods by improving or ensuring food security.
Therefore, adapting the planting and production time in these hazard-prone areas
at peak-risk periods could limit losses and increase communities' resilience.
PMID- 29955309
TI - Climate change, household vulnerability and smart agriculture: The case of two
South African provinces.
AB - The impact of climate-change disasters poses significant challenges for South
Africa, especially for vulnerable rural households. In South Africa, the impact
of climate change at the local level, especially in rural areas, is not well
known. Rural households are generally poor and lack resources to adapt to and
mitigate the impact of climate change, but the extent of their vulnerability is
largely not understood. This study looked at the micro-level impact of climate
change, evaluated household vulnerability and assessed alternative adaptation
strategies in rural areas. The results indicate that climate change will hit crop
yields hard and that households with less capital are most vulnerable. These
households consist of the elderly and households headed by females. Households
that receive remittances or extension services or participate in formal savings
schemes in villages are less vulnerable. The results suggest that households need
to move towards climate-smart agriculture, which combines adaptation, mitigation
and productivity growth.
PMID- 29955310
TI - Community led total sanitation for community based disaster risk reduction: A
case for non-input humanitarian relief.
AB - Sanitation related diseases have become endemic in southern Africa resulting in
increased sanitation and hygiene morbidity and mortality. The region has
experienced 318 400 cases of cholera and diarrhoea outbreaks between 2006 and
2012. There is insufficient financing for sanitation and hygiene activities, as
people lack basic sanitation services, they engage in open defecation, the
primary cause of faecal oral disease transmission. This study investigated
Community Led Total Sanitation (CLTS), subsidy free, community based disaster
risk reduction approach, for open defecation reduction, in four constituencies in
Swaziland. Data collected from households, through a knowledge, attitudes and
practices (KAP) survey illustrated that with appropriate training, involvement of
traditional and community leaders, CLTS minimises open defecation. There is need
of participatory rural appraisal through regular community monitoring and
feedback meetings, as the disgust generated especially for women and youth,
through the meetings, as well as group dynamics, steer the sustained construction
and use of sanitation facilities. Lack of coordination between Non-Governmental
Organisations (NGOs) leads to slow improvement of sanitation coverage, wherein
the same communities are promoting CLTS and others are promoting Subsidy Based
Sanitation Intervention (SBSI) which involves subsidies. It is recommended that
there be coordination between partners for harmonisation of messages and an
integration of the CLTS and SBSI approaches.
PMID- 29955311
TI - The changing climate and human vulnerability in north-central Namibia.
AB - North-central Namibia is more vulnerable to effects of climate change and
variability. Combined effects of environmental degradation, social vulnerability
to poverty and a changing climate will compromise subsistence farming in north
central Namibia (NCN). This will make subsistence and small-scale farmers in the
region more vulnerable to projected changes in the climate system. Thus, the aim
of this article was to examine factors contributing to subsistence farmers'
vulnerability to impacts of climate change. The article further discusses
different aspects of human vulnerability and existing adaptation strategies in
response to impacts of climate related disasters experienced over the past three
to four decades in NCN. Qualitative and quantitative research approaches and
methodology were employed to obtain information from subsistence farmers in north
central Namibia. The sociodemographic characteristics of Ohangwena, Oshana and
Omusati Region reveals high levels of unemployment, high adult and elderly
population and high dependency on agricultural livelihood system. These
indicators help understand levels of household vulnerability. The study concludes
that households interviewed revealed low levels of adaptive capacity due to
exposure to climate risks and combined effects of social, political and cultural
factors. This article provided an understanding that is required to inform the
adaptation pathways relevant for NCN.
PMID- 29955312
TI - Menstrual hygiene - A salient hazard in rural schools: A case of Masvingo
district of Zimbabwe.
AB - Active participation of the girl child in development is hampered by Menstrual
Hygiene Management (MHM) challenges. MHM is an important gender issue and a
critical component in holistic human development. It affects about 25% of the
global population aged between 15 and 49 years. Water, sanitation and hygiene
(WASH) interventions in schools have not prioritised MHM, thus exposing girls and
the entire school community to health related hazards. The study explored
knowledge, attitudes and community practices, and investigated the impact of
religious and cultural beliefs on MHM and how they impact on the girl child in
Masvingo district. The survey was largely qualitative and employed methodologies
of document analysis, Focus Group Discussions (FGD) and structured interviews.
Participants included four churches, 13 NGOs, eight government departments and 40
women. Findings revealed deeply embedded power relations, a culture of silence
around MHM, noninvolvement of men in MHM issues, limited availability in terms of
information, and a girl unfriendly infrastructure, and limited access to
menstrual hygiene products due to poverty and poor management and disposal
practices. Resultant effects ranged from poor class participation, lack of
concentration and constrained interactions with peers and teachers, low self
esteem, anxiety and the general feeling of being discriminated against. Results
confirmed the need for increased awareness initiatives on MHM in a bid to tackle
inherent religious and cultural beliefs that are a barrier to effective holistic
implementation of WASH interventions that empower women and girls. Lobbying
government to provide an appropriate policy framework, education and training,
construction of girl friendly sanitary facilities, exploring and capitalisation
of local production of Reusable Menstrual Pads (RUMPS), more research targeting
children living with disabilities, those living in refugee and makeshift camps
and Orphans and Vulnerable Children (OVC), are some of the recommendations coming
out of the study.
PMID- 29955313
TI - Investigating the knowledge and preparedness of proximal residents to a general
emergency event at the Koeberg Nuclear Power Station.
AB - Ward 23 in the City of Cape Town South Africa is situated within 16 km of Koeberg
Nuclear Power Station (KNPS). Massive investments were made to provide the 13 800
residents of Ward 23 with information on emergency preparedness and evacuation
procedures in case of a general-emergency event at KNPS. However, it is not known
whether these efforts to inform and prepare the proximal residents for a general
emergency have been effective or not. The objective of this study was to
investigate the level of knowledge of and preparedness for an emergency exhibited
by residents of Ward 23. Data was collected through the distribution of semi
structured questionnaires to 204 residents at the study site to ascertain their
views on the provision and accessibility of emergency information and to find out
whether they utilised this information to prepare themselves. The results
revealed that the majority of interviewed residents had very poor knowledge
concerning emergency procedures, and few had made any effort to prepare
themselves. The majority of better-informed and prepared residents tended to
reside closer to KNPS. The poor levels of knowledge and preparedness are
attributed to residents' lack of awareness concerning the availability of
information, misconceptions regarding a nuclear hazard and a general emergency
event or a lack of incentive to inform themselves due to a perceived high sense
of security and the improbability of such an event occurring. To improve resident
knowledge and preparedness, efforts should be made to advertise the availability
and importance of such emergency information and enhance incentives for residents
to inform themselves.
PMID- 29955314
TI - Drivers, scales and contexts of disaster risk: An editorial introduction.
PMID- 29955315
TI - Communal farming, climate change adaptation and the media in Zimbabwe.
AB - Climate change is destroying Zimbabwean communal farmers' agricultural activities
- a source of living for most people. As communal farmers struggle to adapt, the
media is expected to assume a fundamental theoretical role of educating and
informing them about the appropriate adaptation techniques. Located in Umguza
District in Matabeleland North Province, the study explored how communal farmers
created meaning out of climate change media content and its influence on their
agricultural practices from October 2014 to April 2015. In doing so, the study
used the Two-Step Flow theory and Hall's Encoding and Decoding Model. Entrenched
in pragmatism, the study embedded quantitative techniques at different stages.
Multistage sampling combining Simple Random Sampling (SRS), purposive and
systematic sampling techniques was used to identify the 263 households for semi
structured questionnaires, direct observations and in-depth interviews. The
findings were analysed using Statistical Package for the Social Sciences (SPSS),
thematic analysis and pattern matching. The results show that personal
observations; print, broadcast and online media; and opinion leaders were the
main sources of climate change information. The radio was the most used medium in
communicating climate change adaptation though it was the second most accessed
after mobile phones. Conservation Agriculture and planting of drought-resistant
crops were some of the adaptation techniques communicated in the media. When
interacting with media content, communal farmers create their own meaning
influenced by their cultural values, resulting in some adopting, rejecting or
modifying certain adaptation techniques. The study concludes that opinion leaders
are fundamental in communal farmers' interaction with media but their influence
must not be overestimated.
PMID- 29955316
TI - Evaluating farmers' adaptation strategies to climate change: A case study of Kaou
local government area, Tahoua State, Niger Republic.
AB - The study discusses local farmers' strategies of coping with and building
resilience against the negative impact of climate change. Information for the
discussion was from data collected using a set of structured questionnaires from
interviews scheduled with 128 farmers. The questionnaire was based on previous
literature and direct reconnaissance interview with farmers, which culminated in
13 strategies used for the study being reported. For each question, respondents
were asked to choose their best and worst strategies. Thus, the difference
between the best and worst strategies consistent with random utility theory has
been used for the modelling. Results show that semi-transhumance, various
handicrafts making, rural migration, small-scale vegetable production and small
scale river exploitation were the most important strategies identified, whilst
water transport and vending, shifting cultivation, gypsum mining, gathering and
trading of wild fruits and edible plants as well as cattle and sheep fattening
were the least appreciated strategies identified amongst the farmers facing
climate change. These findings are therefore imperative for planning farmers'
capacity-building and resilience against climate change projects to ensure
sustainability in the study area.
PMID- 29955317
TI - Information and communication technologies and gender in climate change and green
economy: Situating women's opportunities and challenges in Zambian policies and
strategies.
AB - Zambia's 2012 report on the United Nations Conference on Sustainable Development
(RIO +20) identifies existing opportunities on the country's transitioning to
green economy. The RIO +20 conference of 2012 has resulted in new momentum in
addressing problems of sustainable development. However, this article argues that
there are practical challenges that require paying attention to, especially those
involving women. The article addressed one key question: To what extent can women
participate in the transitioning process to green economy in Zambia and what
opportunities and challenges exists? The study used document analysis to answer
the above question. National policy documents were reviewed to understand
interventions on environmental management. Whilst going through the documents,
the study used gender analysis frameworks (education, skills, roles in family and
society, access to infrastructure) to bring out qualitative and quantitative
information on women. Using suggested green economy interventions in the
literature as benchmark, qualitative analysis was used to project possible
participation of women in green economy activities and possible challenges to be
faced. The study found that participation of women will be limited despite
existing opportunities because of challenges of access to information and
communication technology infrastructures, low educational levels and skills and
financial constraints. As Zambia undergoes a transitioning process, these
limitations should be addressed in planned green economy policies and
interventions to maximise benefits.
PMID- 29955318
TI - Inclusion of climate change strategies in municipal Integrated Development Plans:
A case from seven municipalities in Limpopo Province, South Africa.
AB - The Intergovernmental Panel on Climate Change (IPCC) has made it clear that
anthropogenic greenhouse gasses are the main cause of observed global warming
that leads to climate change. Climate change is now a global reality. In the
South African political set-up, local municipalities are the structures that are
in direct contact with communities and they draw up Integrated Development Plans
(IDPs), which are reviewed and upgraded annually. The article seeks to
investigate the extent to which climate change adaptation and mitigation
strategies are embedded IDPs in seven vulnerable municipalities in the Limpopo
Province. The article conducted an in-depth content analysis of the IDPs of the
seven municipalities and the results have revealed that these municipalities have
not included adaptation and mitigation strategies adequately in their IDPs
despite being the most vulnerable municipalities in the province. The article
concludes that these municipalities have not as yet institutionalised climate
change in their daily operations, planning and decision making. To this end, the
paper recommends that local municipalities should include climate change
adaptation and mitigation strategies in their IDPs.
PMID- 29955319
TI - The double tragedy of agriculture vulnerability to climate variability in Africa:
How vulnerable is smallholder agriculture to rainfall variability in Ghana?
AB - This article analysed vulnerability of smallholder agriculture to climate
variability, particularly the alternating incidences of drought and heavy
precipitation events in Ghana. Although there is an unmet need for understanding
the linkages between climate change and livelihoods, the urgent need for climate
change adaptation planning (CCAP) in response to climate change makes
vulnerability assessment even more compelling in development research. The data
for analysis were collected from two complementary studies. These included a
regional survey in the Upper West Region and an in-depth study in three selected
communities in the Sissala East District. The results showed that smallholder
agriculture is significantly vulnerable to climate variability in the region and
that three layers of vulnerability can be identified in a ladder of
vulnerability. Firstly, farmers are confronted with the double tragedy of
droughts and heavy precipitation events, which adversely affect both crops and
livestock. Secondly, farmers have to decide on crops for adaptation, but each
option - whether indigenous crops, new early-maturing crops or genetically
modified crops - predisposes farmers to a different set of risks. Finally, the
overall impact is a higher-level vulnerability, namely the risk of total
livelihood failure and food insecurity. The article recommended CCAP and an
endogenous development (ED) approach to addressing agriculture vulnerability to
climate variability within the framework of decentralisation and local governance
in Ghana.
PMID- 29955320
TI - Information and communication technology and climate change adaptation: Evidence
from selected mining companies in South Africa.
AB - The mining sector is a significant contributor to the gross domestic product of
many global economies. Given the increasing trends in climate-induced disasters
and the growing desire to find lasting solutions, information and communication
technology (ICT) has been introduced into the climate change adaptation mix.
Climate change-induced extreme weather events such as flooding, drought,
excessive fog, and cyclones have compounded the environmental challenges faced by
the mining sector. This article presents the adoption of ICT innovation as part
of the adaptation strategies towards reducing the mining sector's vulnerability
and exposure to climate change disaster risks. Document analysis and systematic
literature review were adopted as the methodology. Findings from the study
reflect how ICT intervention orchestrated changes in communication patterns which
are tailored towards the reduction in climate change vulnerability and exposure.
The research concludes with a proposition that ICT intervention must be part of
the bigger and ongoing climate change adaptation agenda in the mining sector.
PMID- 29955321
TI - Is green economy achievable through championing green growth? A local government
experience from Zambia.
AB - The need to enhance environmental sustainability, sustainable development and
growth that takes into account the well-being of the people and nature because of
the increased production and consumption of goods and services is the major
driver to the introduction of green economy in Zambia and countries in southern
Africa. This article examines the extent to which local government in Zambia has
embraced green growth and green economy and critically analyses the concept of
green economy and green growth. This study is based on a review of planning and
policy documents, a household questionnaire survey and interviews with various
institutions, planners and rural development organisations. A number of policies
implemented at the local government level were analysed and reflected upon
irrespective of whether they contain the components of green growth and green
economy and the extent to which they contribute to attaining green economy. The
article argues that the need for economic diversification is important as far as
green economy is concerned. The article recommends the need to invest in research
and development in order to find more carbon-free economic activities. The
conclusion is that local government is key to achieving green growth and green
economy, because it is involved at all levels, from policy formulation to
implementation.
PMID- 29955322
TI - Mainstreaming biodiversity and wildlife management into climate change policy
frameworks in selected east and southern African countries.
AB - The Rio+20 outcomes document, the Future We Want, enshrines green economy as one
of the platforms to attain sustainable development and calls for measures that
seek to address climate change and biodiversity management. This paper audits
climate change policies from selected east and southern African countries to
determine the extent to which climate change legislation mainstreams biodiversity
and wildlife management. A scan of international, continental, regional and
national climate change policies was conducted to assess whether they include
biodiversity and/or wildlife management issues. The key finding is that many
climate change policy-related documents, particularly the National Adaptation
Programme of Actions (NAPAs), address threats to biodiversity and wildlife
resources. However, international policies like the United Nations Framework
Convention on Climate Change and Kyoto Protocol do not address the matter under
deliberation. Regional climate change policies such as the East African
Community, Common Market for Eastern and Southern Africa and African Union
address biodiversity and/or wildlife issues whilst the Southern African
Development Community region does not have a stand-alone policy for climate
change. Progressive countries like Rwanda, Uganda, Tanzania and Zambia have
recently put in place detailed NAPAs which are mainstream responsive strategies
intended to address climate change adaptation in the wildlife sector.
PMID- 29955323
TI - Climate change in semi-arid Malawi: Perceptions, adaptation strategies and water
governance.
AB - Climate change and variability are a threat to sustainable agricultural
production in semi-arid areas of Malawi. Overdependence on subsistence rain-fed
agriculture in these areas calls for the identification of sustainable adaptation
strategies. A study was therefore conducted in Chikwawa, a semi-arid district in
southern Malawi, to: (1) assess community's perception of a changing climate
against empirical evidence, (2) determine their local adaptive measures, (3)
evaluate the potential of irrigated agriculture as an adaptive measure in
household food security and (4) challenges over access to available water
resources. The study employed focus group discussions and key informant
interviews to assess people's perceptions of climate change and variability and
their desired interventions. To validate the people's perceptions, rainfall and
temperature data for the period 1960-2010 were analysed. A participatory complete
randomised experimental design in both rain-fed and dry season-irrigated
conditions was conducted to assess a maize cropping system that would improve
adaptation. The study established persistent declining yields from rain-fed
production in part because of perennial rainfall failure. In response, the
community has shifted its focus to irrigation as an adaptation strategy, which
has in turn triggered water conflicts in the community over the control of the
resource. Water legislation however fails to adequately provide for rules
governing sharing of water resources between various stakeholders. This article
therefore recommends development of an appropriate institutional framework that
forms a strong basis for equitable distribution of water for irrigation in areas
most vulnerable to extreme climate events - including droughts and floods.
PMID- 29955324
TI - The role of communities in sustainable land and forest management: The case of
Nyanga, Zvimba and Guruve districts of Zimbabwe.
AB - Forest benefit analysis is vital in ensuring sustainable community-based natural
resources management. Forest depletion and degradation are key issues in rural
Zimbabwe and strategies to enhance sustainable forest management are continually
sought. This study was carried out to assess the impact of forests on communities
from Nyanga, Guruve and Zvimba districts of Zimbabwe. It is based on a Big
Lottery Fund project implemented by Progressio-UK and Environment Africa. It
focuses on identifying replicable community forest and land management strategies
and the level of benefits accruing to the community. Analysis of change was based
on the Income and Food Security and Forest benefits, which also constitutes the
tools used during the research. The study confirms the high rate of deforestation
and the increased realisation by communities to initiate practical measures aimed
at protecting and sustaining forest and land resources from which they derive
economic and social benefits. The results highlight the value of community
structures (Farmer Field Schools and Environmental Action Groups) as conduits for
natural resource management. The interconnectivity among forests, agricultural
systems and the integral role of people are recognised as key to climate change
adaptation.
PMID- 29955325
TI - The use of and obstacles to social learning in climate change adaptation
initiatives in South Africa.
AB - Global environmental change will have major impacts on ecosystems and human
livelihoods while challenging the adaptive capacity of individuals and
communities. Social learning, an ongoing adaptive process of knowledge
generation, reflection and synthesis, may enhance people's awareness about
climate change and its impacts, with positive outcomes for their adaptive
capacity. The objectives of this study were to assess the prevalence of factors
promoting social learning in climate change adaptation initiatives in South
Africa. An online survey was used to obtain the views of decision makers in
government and non-governmental organisations about the presence of personal
factors and organisational factors that promote social learning. Descriptive
analysis was used to assess these issues. The findings provide some evidence of
social learning in climate change adaptation projects in South Africa, with the
majority of respondents indicating that personal social learning indicators were
present. Mechanisms for improved conflict resolution were, however, less
prevalent. The organisational and governance-related barriers to implementation
also presented significant challenges. Some of the main organisational barriers
were short timeframes for implementing projects, inadequate financial resources,
political interference, shortcomings in governance systems and lack of knowledge
and expertise in organisations. There is a need for organisations to promote
social learning by ensuring that their organisational environment and governance
structures are conducive for their employees to embrace social learning. This
will help contribute to the overall success of climate change adaptation
initiatives.
PMID- 29955326
TI - Sociocultural factors and perceptions associated with voluntary and permanent
relocation of flood victims: A case study of Sekondi-Takoradi Metropolis in
Ghana.
AB - Flooding is a major problem in many developing urban centres in Ghana, including
the Sekondi-Takoradi Metropolis (STM). Residents who are living close to the
Anankwari, Kansawura and Whin rivers in the metropolis often experience flooding
when the rivers overflow their banks, resulting in lives being lost, people being
displaced and properties being destroyed. One durable solution to the flooding
problem is voluntary and permanent relocation of 'vulnerable' residents; but this
form of solution cannot be achieved without a clear understanding of the
sociocultural factors that influence the decision-making process. This study
uniquely investigated the sociocultural and economic factors affecting voluntary
and permanent relocation of flood victims, using Eshiem, Kansawurodo and Whindo
communities as a case study. Employing a mixed cross-sectional design method, 207
heads of households were selected to fill in questionnaires; interviews were
conducted with nine representatives of the traditional councils, and areas
affected by flooding were photographed. The findings show that voluntary and
permanent relocation was overlooked by most flood victims due to perceived
inability to rent new places owing to low incomes, fear of losing income
generating ventures that serve as sources of livelihoods, hope of gaining income
from the oil production within the region and the need for restitution from
government before evacuation. From a sociocultural viewpoint, they felt
uncomfortable with losing ancestral lands and landed properties as well as
breaking long-standing ties with their community folks and other networks. Flood
victims' willingness to stay in the flood-prone communities was also influenced
by duration of stay in the communities and ownership of landed assets. When
considering voluntary and permanent relocation of flood victims as a durable
solution in the future, these sociocultural and economic factors need to be
carefully considered.
PMID- 29955327
TI - Fire disaster preparedness and situational analysis in higher learning
institutions of Tanzania.
AB - Fire disasters are accompanied with devastating impact affecting both lives and
properties. The magnitude of the impacts has been severe in places with low
levels of fire disaster preparedness. A study was conducted in Dar es Salaam,
Tanzania, to investigate the level of fire disaster preparedness considering the
availability and condition of firefighting facilities as well as the knowledge on
fire management among the selected 10 higher learning institutions. Information
for the buildings was obtained from the interviews with the managers of the
buildings and field observations; information on the user's preparedness was
obtained from interviews using structured questionnaire conducted with the users
of the buildings including the visitors. Results from the studied buildings
indicated that 60% of the firefighting facilities were not regularly serviced;
50% stored some hazardous materials; 70% of them had not enough water storage for
firefighting purposes; 60% had no identifiable fire assembly points; and 90% of
the sessions conducted in the buildings involved more than 100 people in a single
venue. Further results indicated that 51% of the respondents were not able to
operate the installed firefighting facilities; 80.7% of the respondents had never
received any training on firefighting and prevention; 95.6% of the respondents
had never participated in any fire drills; and 81.5% of them were not aware of
the fire responder's contacts. General situation indicated that higher learning
institutions are not well prepared to manage fire outbreaks suggesting that plans
to rectify the situation are imperative.
PMID- 29955328
TI - Assessing social vulnerability to drought in South Africa: Policy implication for
drought risk reduction.
AB - The aim of this article was to assess and identify social vulnerability of
communal farmers to drought in the O.R. Tambo district in the Eastern Cape
province of South Africa using a survey data and social vulnerability index
(SoVI). Eleven social vulnerability indicators were identified using Bogardi,
Birkman and Cardona conceptual framework. The result found that an SoVI estimated
for O.R. Tambo district was very high with a Likert scale of 5 for cultural
values and practices, security or safety, social networks, social dependence,
preparedness strategies and psychological stress attributed for the high value of
social vulnerability to drought. Indigenous knowledge and education had an SoVI
value of 2, which was of low vulnerability, contributing positively to resilience
to drought. The study also found that government involvement in drought risk
reduction is limited; as a result, the study recommends that a national,
provincial and district municipalities policy on drought risk reduction and
mitigation should be developed.
PMID- 29955329
TI - Cointegration analysis of vulnerability index and standardised precipitation
index in Mafeteng district, Lesotho.
AB - Given the high poverty levels in Africa, with most countries' economy and
populations' livelihood dependent on rain-fed agriculture, land degradation among
other environmental hazards has proven to be a major threat to economic growth
and food insecurity, respectively. Drought, which is on the increase at the
global level and said to create over 78% of other hazards, has aggravated land
degradation. Dry conditions lessen soil particles cohesion force, thereby
increasing susceptibility of such soils to be lost by wind and water. The current
study aimed at estimating land degradation from drought hazard index,
standardised precipitation index (SPI) over the drought declared district of
Mafeteng Lesotho. Data were provided by Lesotho Meteorological Services for a
period of 30 years (1984-2014). All missing values that existed in the collected
precipitation data were filled with average values of the months with data. The
computation of SPI was performed by using DrinC software in SPI-3 and SPI-Annual
time step. The results revealed a constant condition of land degradation
vulnerability over a 30-year period, implying a continuous loss of soil
fertility, agricultural gross domestic product (GDP), water and bio-energy,
malnutrition and increased poverty levels.
PMID- 29955330
TI - The role of cooperatives in sustaining the livelihoods of rural communities: The
case of rural cooperatives in Shurugwi District, Zimbabwe.
AB - The main focus of the research was to analyse the role of cooperatives in
sustaining the livelihoods of local rural communities in Shurugwi District in
Zimbabwe. Descriptive survey design was used in this mixed method approach to the
study. A questionnaire, interviews and observation methods were employed as the
main research instruments. Purposive sampling technique was adopted and data were
collected from government officials and from members of the six cooperatives in
Shurugwi District. A total of 50 research participants were involved in the
study. It was found that cooperatives were established as a strategy to sustain
livelihoods of rural communities. With the adoption of cooperatives, people in
the rural communities managed to generate employment, boost food production,
empower the marginalised, especially women, and promote social cohesion and
integration, thereby improving their livelihoods and reducing poverty. Most
cooperatives face a number of challenges that include lack of financial support,
poor management and lack of management skills, and lack of competitive markets to
sell their produce. The study recommends that the government and the banking
sector render financial support to cooperatives in rural communities to allow
them to expand and diversify their business operations; constant training on
leadership and management skills is provided to cooperatives' members. There is
also a need for cooperatives, especially those in the agricultural sector, to
form some producer associations so as to easily market their produce. Lastly, the
study recommends that future research should focus on investigating issues that
hinder the growth of the cooperative movement in rural communities of Zimbabwe.
It is hoped that policy-makers, the academia and communities would benefit from
the study.
PMID- 29955331
TI - Cassava production as a climate change adaptation strategy in Chilonga Ward,
Chiredzi District, Zimbabwe.
AB - This study sought to pilot a range of long-term adaptation measures in the
agriculture sector because of climate change shocks. Past droughts in Zimbabwe
have had devastating environmental and socio-economic impacts in rural areas
where livelihoods mainly depend on agriculture. Over the past few years, many
parts of Zimbabwe have been experiencing extreme events. The study sought to
address the following objectives to describe smallholder farmers' knowledge of
climate change variability and change in Chilonga Ward and to explore the
potential of cassava production as a climate change adaptation strategy in
Chiredzi. An assessment of the impact of cassava production on rural livelihoods
as a climate change adaptation strategy was also done. Focus group discussions,
in-depth interviews, desk research and observation were the tools used to collect
data. The results show that cassava has an extensive root system that can
penetrate poor soils which may not support crops like maize. Zimbabwe has to
increase cassava production as its tubers can be value added to produce a range
of products that include livestock feed and porridge.
PMID- 29955332
TI - Climate change: A threat towards achieving 'Sustainable Development Goal number
two' (end hunger, achieve food security and improved nutrition and promote
sustainable agriculture) in South Africa.
AB - This article aims to assess the impacts of climate change towards the achievement
of Sustainable Development Goal number two (SDG 2) as well as examining the
poverty alleviation strategies by subsistence farmers in South Africa. Widespread
hunger and poverty continue to be among the most life-threatening problems
confronting mankind. Available statistics show that global poverty remains a
serious challenge around the world. Across the globe, one in five people lives on
less than $1 a day and one in seven suffers from chronic hunger. Similarly, the
developing world is adversely affected by poverty and hunger. In the sub-Saharan
Africa, research has revealed a higher prevalence of hunger, malnutrition,
poverty and food insecurity. SDG 2 focuses more on eliminating hunger and
promoting sustainable agriculture. The study employed an exploratory design and a
qualitative method. Snowball sampling was used in selecting relevant sources
which led the researchers to other research work on the same field through
keywords and reference lists. The researchers employed discourse analysis to
analyse data. The study discovered that there are numerous potential effects
climate change could have on agriculture. It affects crop growth and quality and
livestock health. Farming practices could also be affected as well as animals
that could be raised in particular climatic areas. The impact of climate change
as well as the susceptibility of poor communities is very immense. The article
concludes that climate change reduces access to drinking water, negatively
affects the health of people and poses a serious threat to food security.
PMID- 29955333
TI - Dynamics of agricultural land and the risk to food insecurity in the Niayes
region of Diamniadio, West Senegal.
AB - Food security is a serious challenge facing West African countries because most
croplands are being degraded. Consequently, agricultural production is being
exceeded by rapid population growth. This study relates the dynamics of
agricultural lands to the level of capacity building for resilience in response
to low productivity and hence to food insecurity in the Niayes region, Senegal,
where lands are presumably suitable for crop production. Factors influencing
changes in surface areas, soil quality and level of resilience were examined
using quantitative and qualitative research methods. Findings showed strong
relationships between a significant decrease (65.25% - 35.54%) in productive
agricultural lands with a range of soil physical and chemical properties (clay to
loamy soil texture; soil pH: 7.0-8.0; soil organic carbon [SOC]: 5.0 g kg-1 -
25.0 g kg-1; effective cations exchangeable capacity [ECEC]: 4.5 Cmol kg-1 - 39.0
Cmol kg-1; cation exchange capacity [CEC]: 8.0 Cmol kg-1 - 34.0 Cmol kg-1) and
food insecurity levels. In the last 5 years, urbanisation and industrialisation
processes have reduced the farmlands by about 26.51% through uncontrolled
construction of buildings and companies, leading to a disappearance of lands.
Such dynamics raises the issue of a risk to food security in a region that
usually provides more than 70% of fruits and vegetables demand for consumption.
These results underline a need for a greater understanding of resilience for a
better management design with a risk prevention plan to ensure food security.
PMID- 29955334
TI - Evaluating the components of social and economic resilience: After two large
earthquake disasters Rudbar 1990 and Bam 2003.
AB - Extensive damages of natural disasters have made resilience a focus of disaster
management plans in order to limit damages. The aim of this study was a
comparative evaluation of social and economic resilience in Bam and Rudbar. This
applied research attempted to quantify and compare different dimensions of social
and economic resilience in Bam and Rudbar with a descriptive-analytical method.
Cochran's formula determined the sample size as 330 households from both cities
(a total of 660 households). The indicators of social and economic resilience
were identified from the literature, and then data were collected through a field
study using questionnaires. Data were analysed using multiple linear regression
and feed-forward multilayer perceptron artificial neural network. Results denoted
that several resilient-related socio-economic features were significantly
different for Bam and Rudbar cities, such as the number of earthquakes
experienced, length of stay in current neighbourhood and mean individual and
household income. Mean social and economic resilience scores were significantly
higher for Rudbar (216.3 +/- 33.4 and 30.6 +/- 7.3) compared to Bam (193 +/- 26.5
and 29.4 +/- 7.07) (p < 0.05). In addition, linear regression indicated that an
increase in education level of the household head, length of stay in current
neighbourhood and household income could result in an increase in social and
economic resilience of the households under study. Neural network analysis
revealed that social capital and employment recovery are the most and least
effective factors, respectively, in both cities. In the population under study,
social component, namely, social capital, was the most important determinant of
resilience.
PMID- 29955335
TI - Urban settlements' vulnerability to flood risks in African cities: A conceptual
framework.
AB - In the recent past, the frequency and gravity of large-scale flood disasters have
increased globally, resulting in casualties, destruction of property and huge
economic loss. The destructive flood disaster devastating Louisiana, USA, is a
recent example. Despite the availability of advanced technological capabilities
for dealing with floods in developed nations, flood disasters continue to become
more rampant and disastrous. Developing countries in Africa such as Benin, Ghana,
Nigeria, Senegal and Sudan have recently experienced severe flooding, leaving a
considerable number of human casualties and thousands displaced. In African
cities, most vulnerable urban residents usually have lesser capacity and fewer
resources to recover from the shocks of disaster as a result of the failure of
governments to build human security for poor African residents. Many scholars
have acknowledged the lack of appropriate vulnerability assessment frameworks and
policies, questioning the efficiency and effectiveness of the tested models in
Africa. The ability to accurately identify, measure and evaluate the various
vulnerabilities of affected people and communities is a right step towards
reducing disaster risk. This article aimed at developing a framework for
assessing urban settlements' vulnerability to flood risks in Africa. The
framework is currently being tested to assess various dimensions of vulnerability
drivers in three urban communities in Ibadan metropolis, the third largest city
in Nigeria, focusing more on flood risk perceptions and behaviour of the risk
bearers. It uses participatory and mixed method approaches to socially construct
vulnerability of populations at risk. This model emanates from the evaluation of
considerable relevant literature and an array of vulnerability assessment
frameworks. It integrates some approaches that are applicable to African cities
in a bid to create a versatile tool to assess, identify and mitigate the effects
of flood disaster risk and reduce urban poor's vulnerability to natural and human
induced hazards.
PMID- 29955336
TI - Vulnerability of human settlements to flood risk in the core area of Ibadan
metropolis, Nigeria.
AB - Flood disasters continue to wreak havoc on the lives of millions of people
worldwide, causing death and massive economic losses. In most African cities,
residents and their assets are among the most vulnerable to flood risks in the
world. The nature and scale of this urban risk are changing because of the
dynamic patterns of land use, unplanned growth and impacts of climate change.
Flood risk is the product of the flood hazards, the vulnerability and exposure of
the people and their physical environment. In order to minimise flood disaster,
there is an urgent need to understand, invest in flood disaster risk reduction
for resilience and to enhance disaster preparedness for an effective response as
articulated in the recent Sendai Framework for Disaster Risk Reduction. This
research utilises a new proposed flood vulnerability assessment framework for
flood risk in a traditional community in the heart of Ibadan metropolis, in the
context of their households' exposure, susceptibility and coping capacity through
a well-designed questionnaire survey. The study uses descriptive and inferential
statistics techniques to provide a detailed understanding of the vulnerability
profiles of the community and the levels of residents' preparedness to mitigate
the flood risk. The results of the statistical analysis show that there is a
significant relationship between residents' flood awareness and having previous
flood experience, but there is no significant association between their awareness
of risk and the level of preparedness for flooding. To minimise exposure and
vulnerability to flood risk, we advocate effective adaptation policies to achieve
disaster risk reduction and resilience on flood risk rather than focusing merely
on reactive measures after disaster strikes.
PMID- 29955337
TI - Chronological trends in maximum and minimum water flows of the Teesta River,
Bangladesh, and its implications.
AB - Bangladesh shares a common border with India in the west, north and east and with
Myanmar in the southeast. These borders cut across 57 rivers that discharge
through Bangladesh into the Bay of Bengal in the south. The upstream courses of
these rivers traverse India, China, Nepal and Bhutan. Transboundary flows are the
important sources of water resources in Bangladesh. Among the 57 transboundary
rivers, the Teesta is the fourth major river in Bangladesh after the Ganges, the
Brahmaputra and the Meghna and Bangladesh occupies about 2071 km2. The Teesta
River floodplain in Bangladesh accounts for 14% of the total cropped area and
9.15 million people of the country. The objective of this study was to
investigate trends in both maximum and minimum water flow at Kaunia and Dalia
stations for the Teesta River and the coping strategies developed by the
communities to adjust with uncertain flood situations. The flow characteristics
of the Teesta were analysed by calculating monthly maximum and minimum water
levels and discharges from 1985 to 2006. Discharge of the Teesta over the last 22
years has been decreasing. Extreme low-flow conditions were likely to occur more
frequently after the implementation of the Gozoldoba Barrage by India. However, a
very sharp decrease in peak flows was also observed albeit unexpected high
discharge in 1988, 1989, 1991, 1997, 1999 and 2004 with some in between April and
October. Onrush of water causes frequent flash floods, whereas decreasing flow
leaves the areas dependent on the Teesta vulnerable to droughts. Both these
extreme situations had a negative impact on the lives and livelihoods of people
dependent on the Teesta. Over the years, people have developed several risk
mitigation strategies to adjust with both natural and anthropogenic flood
situations. This article proposed the concept of 'MAXIN (maximum and minimum)
flows' for river water justice for riparian land.
PMID- 29955338
TI - Quantitative risk analysis using vulnerability indicators to assess food
insecurity in the Niayes agricultural region of West Senegal.
AB - There is an increasing need to develop indicators of vulnerability and adaptive
capacity to determine the robustness of response strategies over time and better
understand the underlying processes. This study aimed to determine levels of risk
of food insecurity using defined vulnerability indicators. For the purpose of
this study, factors influencing food insecurity and different vulnerable
indicators were examined using quantitative and qualitative research methods.
Observations made on the physical environment (using tools for spatial analysis)
and socio-economic surveys conducted with local populations have quantified
vulnerability indicators in the Niayes agricultural region. Application of the
Classification and Regression Tree (CART) model has enabled us to quantify the
level of vulnerability of the zone. The results show that the decrease in
agricultural surface areas is the most discriminant one in this study. The speed
of reduction of the agricultural areas has specially increased between 2009 and
2014, with a loss of 65% of these areas. Therefore, a decision-making system,
centred on the need for reinforcing the resilience of local populations, by
preserving the agricultural vocation of the Niayes region and even in the
Sahelian regions requires support and extension services for the farmers in order
to promote sustainable agricultural practices.
PMID- 29955339
TI - Assessing newly introduced climate change adaptation strategy packages among
rural households: Evidence from Kaou local government area, Tahoua State, Niger
Republic.
AB - This research discusses new strategies developed and introduced by national and
international partners to help farmers in building adaptative capacity against
the negative externalities of climate change. The purpose of this study is to
determine and to assess the most important adaptation strategies introduced by
development partners. Based on the recognition interview with farmers and
synthesis of previous research, 13 strategies were compiled and included in the
study. Thus, an advance in the balanced incomplete block design was used to
design the questionnaire served as data collection tools. For each question,
respondents were asked to choose their best and their worst strategies. Thus, the
difference between the best and worst strategies consistent with random utility
theory was used for the modelling. Results show that herd rebuilding, human
capacity building, introduction of fishing, water and soil conservation
activities, introduction of leafy vegetable such as Moringa oleifera, financial
credit, forage seed marketing and introduction of agriculture inputs were the
most important strategies, while the support to vegetable production, income
generating activities, the use of agricultural improved seed varieties, anti-fire
band making and cereal bank introduction were the least important adaptation
strategies for farmers. These results are therefore essential for the
dissemination of adaptation strategies, thereby stimulating and maintaining
sustainability development actions in the study area.
PMID- 29955340
TI - Collaborative risk governance in informal urban areas: The case of Wallacedene
temporary relocation area.
AB - Community-based disaster risk management (CBDRM) is an emancipatory approach that
aims to empower local communities in reducing their own risks. A community risk
assessment (CRA) is an essential element of CBDRM, incorporating highly
participatory processes of hazard identification and vulnerability analysis. By
incorporating local knowledge and insights, together with those contributed by
other external role players, the nature of local risks can be more accurately
identified, giving consideration to their causal factors, the nature of their
realised impacts or potential effects on a local community and the challenges
posed in addressing them. Reflecting on the process and outcomes of a CRA
conducted in an informal settlement in the Cape Town metropolitan area, this
article describes how one such risk assessment contributed to building local
agency through a process of collaborative engagement. Offered as an example of
possible best practice, it illustrates both the immediate and potentially longer
term benefits to be derived from such a collaborative process, suggesting that a
community-based risk assessment may contribute significantly to building more
resilient communities. It concludes with a consideration of the challenges of
sustaining longer term risk reduction efforts.
PMID- 29955341
TI - Enhancing resilience to landslide disaster risks through rehabilitation of slide
scars by local communities in Mt Elgon, Uganda.
AB - Mass movements are key drivers affecting the utilisation of many farmlands and
consequently the livelihoods in mountains' ecosystems. Numerous expansive
landslide scars can for years remain unusable for crop farming purposes, which is
a major livelihood activity. This article examined the approaches and challenges
faced by local communities in the rehabilitation of landslide-degraded areas in
selected areas of Mt Elgon. Data were collected through field surveys of
purposively selected scars, key informant interviews and focus group discussions
with the local communities. The findings indicate that the local communities have
initiated the rehabilitation of some scars to stabilise the slopes and also
accelerate their quick recovery for beneficial purposes. Community trainings
coupled with awareness and participatory actions during rehabilitation enhance
community preparedness to landslide risks. However, there were noted constraints
including limited resources, incidences of secondary slides, cracks and lack of
adequate knowledge on the existing best practices for the rehabilitation of scars
on deeply weathered soils. Further research should be focussed on generating
relevant knowledge on regeneration rates under different socio-ecological
conditions and for guiding sustainable utilisation of fragile areas.
PMID- 29955342
TI - Social impacts of corruption upon community resilience and poverty.
AB - Corruption at all levels of all societies is a behavioural consequence of power
and greed. With no rulebook, corruption is covert, opportunistic, repetitive and
powerful, reliant upon dominance, fear and unspoken codes: a significant
component of the 'quiet violence'. Descriptions of financial corruption in China,
Italy and Africa lead into a discussion of 'grand', 'political' and 'petty'
corruption. Social consequences are given emphasis but elude analysis; those in
Bangladesh and the Philippines are considered against prerequisites for
resilience. People most dependent upon self-reliance are most prone to its
erosion by exploitation, ubiquitous impediments to prerequisites of resilience -
latent abilities to 'accommodate and recover' and to 'change in order to
survive'. Rarely spoken of to those it does not dominate, for long-term
effectiveness, sustainability and reliability, eradication of corrupt practices
should be prerequisite to initiatives for climate change, poverty reduction,
disaster risk reduction and resilience.
PMID- 29955344
TI - The impact of climate change on food security in South Africa: Current realities
and challenges ahead.
AB - This article aims to examine the impact of climate change on food security in
South Africa. For this purpose, the article adopted a desktop study approach.
Previous studies, reports, surveys and policies on climate change and food
(in)security. From this paper's analysis, climate change presents a high risk to
food security in sub-Saharan countries from crop production to food distribution
and consumption. In light of this, it is found that climate change, particularly
global warming, affects food security through food availability, accessibility,
utilisation and affordability. To mitigate these risks, there is a need for an
integrated policy approach to protect the arable land against global warming. The
argument advanced in this article is that South Africa's ability to adapt and
protect its food items depends on the understanding of risks and the
vulnerability of various food items to climate change. However, this poses a
challenge in developing countries, including South Africa, because such countries
have weak institutions and limited access to technology. Another concern is a
wide gap between the cost of adapting and the necessary financial support from
the government. There is also a need to invest in technologies that will resist
risks on food systems.
PMID- 29955343
TI - Nutritional vulnerability: An assessment of the 2010 feeding food programme in
Mbire district, Zimbabwe, and its impact on pregnant women.
AB - Malnutrition contributes significantly to Zimbabwe's high maternal mortality
rate. The prevalence of malnutrition among vulnerable pregnant women in the Mbire
district of Zimbabwe was studied to establish why they remained vulnerable
despite benefiting from the Vulnerable Group Feeding Programme, a subsidiary of
the World Food Programme. A case study on the demographic characteristics,
nutritional provision of the programme and the vulnerable pregnant women
benefiting from the programme was conducted. One hundred women were purposively
sampled at health centres in the district. A two-stage sampling procedure was
then utilised to select the most food-insecure wards. The two most food-insecure
wards, namely Angwa and Chapoto, were chosen because of their proximity to each
other. A questionnaire was administered to the pregnant women to collect their
demographic information. Practising nurses at the health centres determined the
women's nutritional status and anthropometrics, and they also assessed the food
baskets. Permission to conduct the study was obtained from the relevant
authorities. The results indicated that the food hamper provided by the World
Food Programme was complementary food aid given to all vulnerable members of the
community regardless of the nutritional demands. The supplements that the
pregnant women received were also inadequate to cater for their nutritional needs
or those of the foetuses. It was therefore recommended that the government,
through the Ministry of Health, should make more provisions available for
vulnerable pregnant women in order to reduce the risks facing pregnant women in
the country.
PMID- 29955345
TI - The role of indigenous knowledge in drought risk reduction: A case of communal
farmers in South Africa.
AB - Even though the significance of indigenous knowledge in agriculture is
internationally recognised, the role thereof in disaster risk reduction in South
Africa is not well documented. This article determined the influence of
indigenous knowledge in drought risk reduction in O.R. Tambo district of the
Eastern Cape province (South Africa). Primary data were collected from 87
communal farmers through purposive sampling using a structured questionnaire.
Focus group discussions were also held with the target group (farmers and
extension officers) to gain more information and clarification on indigenous
knowledge. The finding indicated that the majority of respondents (64.4%) relied
on indigenous knowledge in their farming practice and drought risk reduction. Two
thirds (66.7%) of the respondents revealed that indigenous knowledge contributed
to the resilience of farmers towards drought. The respondents unanimously agreed
that indigenous knowledge is losing its significance in farming and drought risk
reduction, because the younger generation did not value it anymore. Lack of
documentation and deterioration of its application by the younger generation were
found to be the main challenge for most respondents. The study concluded that
indigenous knowledge was still an integral part of agricultural practices,
applied drought risk reduction strategies and contributed to resilience against
disasters. Based on the findings, the study recommends that indigenous knowledge
be compiled, documented and published so that all farmers can learn of effective
farming practices, passed on from generation to generation. Community holders of
such information are encouraged to make younger generations aware of the benefits
of indigenous knowledge to promote its usage.
PMID- 29955346
TI - Geographic information systems-based expert system modelling for shoreline
sensitivity to oil spill disaster in Rivers State, Nigeria.
AB - In the absence of adequate and appropriate actions, hazards often result in
disaster. Oil spills across any environment are very hazardous; thus, oil spill
contingency planning is pertinent, supported by Environmental Sensitivity Index
(ESI) mapping. However, a significant data gap exists across many low- and middle
income countries in aspect of environmental monitoring. This study developed a
geographic information system (GIS)-based expert system (ES) for shoreline
sensitivity to oiling. It focused on the biophysical attributes of the shoreline
with Rivers State as a case study. Data on elevation, soil, relative wave
exposure and satellite imageries were collated and used for the development of ES
decision rules within GIS. Results show that about 70% of the shoreline are lined
with swamp forest/mangroves/nympa palm, and 97% have silt and clay as dominant
sediment type. From the ES, six ranks were identified; 61% of the shoreline has a
rank of 9 and 19% has a rank of 3 for shoreline sensitivity. A total of 568 km
out of the 728 km shoreline is highly sensitive (ranks 7-10). There is a clear
indication that the study area is a complex mixture of sensitive environments to
oil spill. GIS-based ES with classification rules for shoreline sensitivity
represents a rapid and flexible framework for automatic ranking of shoreline
sensitivity to oiling. It is expected that this approach would kick-start
sensitivity index mapping which is comprehensive and openly available to support
disaster risk management around the oil producing regions of the country.
PMID- 29955347
TI - Building resilience to food insecurity in rural communities: Evidence from
traditional institutions in Zimbabwe.
AB - Many rural communities that depend on smallholder farming face food insecurity
induced by climate-related disasters. In response, some communities are taking
the initiative to cope and adapt to climate-related disasters. Using case study
material from the Zambezi Valley, Zimbabwe, this article examines how traditional
institutions are enhancing resilience to food insecurity in rural areas. The data
were collected through interviews and focus groups involving traditional leaders,
ward councillors, village civil protection members and villagers selected in the
valley. The findings point to how the Zunde raMambo informal safety net, nhimbe
form of collective work and the practice of share-rearing arrangement to access
draught power help save lives and alleviate food insecurity induced by flood or
drought disasters. The study concludes that the three schemes are evidence of
community reorganisation or change in response to food insecurity. They are a
form of absorptive capacities enabling the community to cope with food
insecurity.
PMID- 29955348
TI - The adaptive capacity of smallholder mixed-farming systems to the impact of
climate change: The case of KwaZulu-Natal in South Africa.
AB - Climate change poses a serious threat to efforts by developing countries to
ensure food security and poverty reduction. The National Development goals of
South Africa envisage the agricultural sector as a key driver for job creation
and economic growth. This article seeks to investigate the adaptive capacity of
the Ncunjane farming community in Msinga, KwaZulu-Natal in response to drought
spells of 2010 and 2014. This article draws on data collected using both
qualitative and quantitative methods in 2011 and later in 2015 with the data
analysed through the Statistical Package for Social Science to determine
significant correlations between variables. Analysis of the vulnerability and
adaptive capacity is performed using conceptual framework. This study found that
both smallholder farmers who engaged in livestock and crop production have
experienced high cattle mortalities and stagnant crop productivity, which in turn
put pressure on already constrained disposable household income because of
increased food costs and agricultural input costs, particularly supplementary
animal feed. Cattle owners were more vulnerable to drought because of poor risk
management and thus became highly dependent on government to provide drought
relief. Application for government drought relief was found not to be effective
in cases of large herds of cattle. Variability of rainfall and prolonged heat
spells has a significant impact on the sustainability of smallholder mixed
farming systems, leaving agriculture as a highly questionable form of livelihood
for rural farming communities such as Msinga. The article recommends strengthened
institutional mechanisms so that stakeholders should play a more meaningful role
within provincial and local agriculture in leveraging government support but
places emphasis on the adoption of innovative strategies that can potentially
yield significantly resilient smallholder mixed-farming systems in the wake of
climate variability.
PMID- 29955349
TI - The relationship between drought and tourist arrivals: A case study of Kruger
National Park, South Africa.
AB - National parks around the world have been recognised as important sources of
nature experiences for both local and international visitors. In South Africa,
national parks are similarly important recreational and nature tourism
attractions. They offer visitors an unparalleled diversity of tourism
opportunities, including game viewing, bush walks and exposure to culture and
history. South African National Parks (SANParks), established in 1926, is one of
the world's leading conservation and scientific research bodies and a leading
agent in maintaining the country's indigenous natural environment. The study aims
to analyse the correlation between drought and the number of tourist arrivals to
the Kruger National Park (KNP). Rainfall data, as well as data on tourist
arrivals at KNP for the period from 1963 to 2015 were obtained from the South
African Weather Services (SAWS) and SANParks, respectively. Rainfall data were
used to determine the drought years at the KNP through computing the Standardised
Precipitation Index (SPI) for various stations around the park. Pearson's
correlation coefficient was used as a statistical measure of the strength of a
linear relationship between drought and tourist arrivals. The results showed that
KNP experienced both negative and positive tourist arrivals, although the former
was the case, tourist arrivals showed an increasing trend. The correlation
relationship showed that 19.36% of the drought years corresponded to a negative
change in tourist arrivals to the park. The results obtained confirm that the
tourism industry is a fragile industry which is prone to environmental, social
and economic state of a region.
PMID- 29955350
TI - Fish farming as an innovative strategy for promoting food security in drought
risk regions of Zimbabwe.
AB - This article examines the implementation of fish farming as an innovative and
economic strategy for promoting food security and dietary diversities among
vulnerable households in drought risk areas of Zimbabwe. The declining climatic
conditions and lack of economic opportunities in Mwenezi district of Zimbabwe
attracted the attention of three non-governmental organisations (NGOs) to
implement fish farming as an innovative mechanism to stimulate food security and
generate employment in the district. The article used a qualitative research
approach that includes semi-structured interviews and secondary data. The
purposive sampling technique was adopted to interview participants in Mwenezi
district who were involved in fish farming to assess and explore the experiences
and benefits they derive from such development projects. Results for the article
revealed that fish farming was well embraced by local communities as it led to
improvements in food security, household income and employment regeneration. The
local government including traditional leadership (Chiefs and Headmen's)
supported the NGO activities as they benefited local communities. The article
concludes that although fish farming was instrumental in regenerating employment,
some participants still fail to participate because of laziness and desire to
maintain dependency syndrome. The article recommends the NGOs to launch awareness
campaigns in rural communities and increase networking with the donor community
which is fundamental in attracting sustainable funding. The government can also
promote fish farming in vulnerable rural communities by providing funding and
capacity building programmes.
PMID- 29946420
TI - Oral aniracetam treatment in C57BL/6J mice without pre-existing cognitive
dysfunction reveals no changes in learning, memory, anxiety or stereotypy.
AB - Background: The piracetam analog, aniracetam, has recently received attention for
its cognition enhancing potential, with minimal reported side effects. Previous
studies report the drug to be effective in both human and non-human models with
pre-existing cognitive dysfunction, but few studies have evaluated its efficacy
in healthy subjects. A previous study performed in our laboratory found no
cognitive enhancing effects of oral aniracetam administration 1-hour prior to
behavioral testing in naive C57BL/6J mice. Methods: The current study aims to
further evaluate this drug by administration of aniracetam 30 minutes prior to
testing in order to optimize any cognitive enhancing effects. In this study, all
naive C57BL/6J mice were tested in tasks of delayed fear conditioning, novel
object recognition, rotarod, open field, elevated plus maze, and marble burying.
Results: Across all tasks, animals in the treatment group failed to show enhanced
learning when compared to controls. Conclusions: These results provide further
evidence suggesting that aniracetam conveys no therapeutic benefit to subjects
without pre-existing cognitive dysfunction.
PMID- 29946421
TI - The unhappy postdoc: a survey based study.
AB - Background: The emerging public discourse about the "broken" postdoc system is
mostly conceptual (with several recent exceptions). The current work offers an
attempt to quantify postdocs' perceptions, goals, and well-being. Methods: A
survey of 190 postdocs in North America. Results: This article first reveals a
surprisingly unhappy postdoc community with low life satisfaction. Second, it
demonstrates how over the course of the fellowship many postdocs lose interest in
the goal of pursuing a tenure track academic position (~20%) or in recommending
the postdoc track to others (~30%). Finally, we find that among a large number of
factors that can enhance life satisfaction for postdocs (e.g., publication
productivity, resources available to them) only one factor stood out as
significant: the degree to which atmosphere in the lab is pleasant and collegial.
Conclusions: Our findings can stimulate policy, managerial, and career
development improvements in the context of the postdoc system.
PMID- 29946422
TI - Simulation and visualization of multiple KEGG pathways using BioNSi.
AB - Motivation: Many biologists are discouraged from using network simulation tools
because these require manual, often tedious network construction. This situation
calls for building new tools or extending existing ones with the ability to
import biological pathways previously deposited in databases and analyze them, in
order to produce novel biological insights at the pathway level. Results: We have
extended a network simulation tool (BioNSi), which now allows merging of multiple
pathways from the KEGG pathway database into a single, coherent network, and
visualizing its properties. Furthermore, the enhanced tool enables loading
experimental expression data into the network and simulating its dynamics under
various biological conditions or perturbations. As a proof of concept, we tested
two sets of published experimental data, one related to inflammatory bowel
disease condition and the other to breast cancer treatment. We predict some of
the major observations obtained following these laboratory experiments, and
provide new insights that may shed additional light on these results. Tool
requirements: Cytoscape 3.x, JAVA 8 Availability: The tool is freely available at
http://bionsi.wix.com/bionsi, where a complete user guide and a step-by-step
manual can also be found.
PMID- 29946431
TI - META-pipe Authorization service.
AB - We describe the design, implementation, and use of the META-pipe Authorization
service. META-pipe is a complete workflow for the analysis of marine metagenomics
data. We will provide META-pipe as a web based data analysis service for ELIXIR
users. We have integrated our Authorization service with the ELIXIR Authorization
and Authentication Infrastructure (AAI) that allows single sign-on to services
across the ELIXIR infrastructure. We use the Authorization service to authorize
access to data on the META-pipe storage system and jobs in the META-pipe job
queue. Our Authorization server was among the first SAML2 service providers that
integrated with ELIXIR AAI. The code is open source at: https://gitlab.com/uit
sfb/AuthService2.
PMID- 29946435
TI - Evaluation of the potential defensive strategy against Influenza A in cell line
models.
AB - Background: Influenza virus can cause both seasonal infections and unpredictable
pandemics. Rapidly evolving avian H5N1 and H7N9 viruses have a potential
pandemic threat for humans. Since avian Influenza can be transmitted by domestic
birds, serving as a key link between wild birds and humans, an effective measure
to control the influenza transmission would be eradication of the infection in
poultry. It is known that the virus penetrates into the cell through binding with
the terminal oligosaccharides - sialic acids (SA) - on the cell surfaces. Removal
of SA might be a potential antiviral strategy. An approach to developing chicken
lines that are resistant to influenza viruses could be the creation of
genetically modified birds. Thus it is necessary to select a gene that provides
defense to influenza. Here we have expressed in cells a range of exogenous
sialidases and estimated their activity and specificity towards SA residues.
Methods: Several bacterial, viral and human sialidases were tested. We adopted
bacterial sialidases from Salmonella and Actinomyces for expression on the cell
surface by fusing catalytic domains with transmembrane domains. We also selected
Influenza A/PuertoRico/8/34/H1N1 neuraminidase and human membrane sialidase (
hNeu3) genes. Lectin binding assay was used for estimation of a alpha (2,3)
sialylation level by fluorescent microscopy and FACS. Results: We compared
sialidases from bacteria, Influenza virus and human. Sialidases from Salmonella
and Influenza A neuraminidase effectively cleaved alpha (2-3)-SA receptors. Viral
neuraminidase demonstrated a higher activity. Sialidases from Actinomyces and
hNeu3 did not show any activity against alpha (2-3) SA under physiological
conditions. Conclusion: Our results demonstrated that sialidases with different
specificity and activity can be selected as genes providing antiviral defence.
Combining chosen sialidases with different activity together with tissue-specific
promoters would provide an optimal level of desialylation. Tissue specific
expression of the sialidases could protect domestic birds from infection.
PMID- 29946437
TI - Successful CRISPR/Cas9 mediated homologous recombination in a chicken cell line.
AB - Background: CRISPR/Cas9 system is becoming the dominant genome editing tool in a
variety of organisms. CRISPR/Cas9 mediated knock out has been demonstrated both
in chicken cell lines and in chicken germ cells that served to generate
genetically modified birds. However, there is limited data about CRISPR/Cas9
dependent homology directed repair (HDR) for avian, even in cell culture. Few
attempts have been made with integrations in safe harbor loci of chicken genome
that induces constitutive expression of the inserted gene. Gene expression under
an endogenous promoter would be more valuable than under a constitutive exogenous
promoter, as it allows the gene expression to be tissue-specific. Methods: Three
gRNAs were chosen to target chicken 3'-untranslated region of GAPDH gene. Cas9
mediated activity in the targeted locus for the gRNAs in DF-1 cells was estimated
by T7E1 assay. To edit the locus, the HDR cassette was added along with
CRISPR/Cas9. The inserted sequence contained eGFP in frame with a GAPDH coding
sequence via P2A and Neomycin resistance gene ( neoR) under cytomegalovirus
promoter. Correct integration of the cassette was confirmed with fluorescent
microscopy, PCR analysis and sequencing. Enrichment of modified cells was done by
G418 selection. Efficiency of integration was assessed with fluorescence
activated cell sorting (FACS). Results: We have established a CRISPR/Cas9 system
to target an endogenous locus and precisely insert a gene under endogenous
control. In our system, we used positive and negative selection to enrich
modified cells and remove cells with undesirable insertions. The efficiency of
CRISPR/Cas9-mediated HDR was increased up to 90% via G418 enrichment. We have
successfully inserted eGFP under control of the chicken GAPDH promoter.
Conclusions: The approach can be used further to insert genes of interest under
control of tissue-specific promoters in primordial germ cells in order to produce
genetically modified birds with useful for biotechnological purposes features.
PMID- 29946439
TI - Blood-derived extracellular proteins as potential biomarkers for the diagnosis of
early ER+ breast cancer and detection of lymph node involvement.
AB - Extracellular vesicles (EV's) are membrane surrounded structures released by
different cell types and are emerging as potential therapeutic and diagnostic
targets in cancer. In the present study, plasma samples derived from 7 patients
with metastatic and non-metastatic ER+ (estrogen receptor positive) breast cancer
(BC) were collected and their respective (EVs) isolated and the protein content
analyzed by mass spectrometry and FunRich analysis. Here we report on the
presence of two putative plasma EV biomarkers (which were absent in healthy
controls samples) that could be used to detect early ER+ breast cancer and for
those with lymph node (LN) involvement However, given the preliminar nature of
the work, further investigation in a larger patient cohort is warranted to
corroborate these findings. If confirmed, these biomarkers could be incorporated
into simple blood test kit for the early detection of those with ER+ breast
cancer and lymph node involvement.
PMID- 29946439
TI - Blood-derived non-extracellular vesicle proteins as potential biomarkers for the
diagnosis of early ER+ breast cancer and detection of lymph node involvement.
AB - Extracellular vesicles (EV's) are membrane surrounded structures released by
different cell types and are emerging as potential therapeutic and diagnostic
targets in cancer. In the present study, plasma samples derived from 7 patients
with metastatic and non-metastatic ER+ (estrogen receptor positive) breast cancer
(BC) were collected and their respective (EVs) isolated and the protein content
analyzed by mass spectrometry and FunRich analysis. Two putative plasma
biomarkers (absent in healthy controls samples) were identified which could be
used to detect early ER+ breast cancer and for those with lymph node (LN)
involvement However, given the current limitations of the EV isolation method
used, it is possible that these biomarkers did not originate from EVs and may
represent blood-derived extracellular proteins. Further work in a larger patient
cohort is warranted to confirm these findings and examine the diagnostic
potential of these biomarkers.
PMID- 29946440
TI - segment_liftover : a Python tool to convert segments between genome assemblies.
AB - The process of assembling a species' reference genome may be performed in a
number of iterations, with subsequent genome assemblies differing in the
coordinates of mapped elements. The conversion of genome coordinates between
different assemblies is required for many integrative and comparative studies.
While currently a number of bioinformatics tools are available to accomplish this
task, most of them are tailored towards the conversion of single genome
coordinates. When converting the boundary positions of segments spanning larger
genome regions, segments may be mapped into smaller sub-segments if the original
segment's continuity is disrupted in the target assembly. Such a conversion may
lead to a relevant degree of data loss in some circumstances such as copy number
variation (CNV) analysis, where the quantitative representation of a genomic
region takes precedence over base-specific accuracy. segment_liftover aims at
continuity-preserving remapping of genome segments between assemblies and
provides features such as approximate locus conversion, automated batch
processing and comprehensive logging to facilitate processing of datasets
containing large numbers of structural genome variation data.
PMID- 29946442
TI - Automation of ReactomeFIViz via CyREST API.
AB - Pathway- and network-based approaches project seemingly unrelated genes onto the
context of pathways and networks, enhancing the analysis power that cannot be
achieved via gene-based approaches. Pathway and network approaches are routinely
applied in large-scale data analysis for cancer and other complicated diseases.
ReactomeFIViz is a Cytoscape app, providing features for researchers to perform
pathway- and network-based data analysis and visualization by leveraging manually
curated Reactome pathways and highly reliable Reactome functional interaction
network. To facilitate adoption of this app in bioinformatics software pipeline
and workflow development, we develop a CyREST API for ReactomeFIViz by exposing
some major features in the app. We describe a use case to demonstrate the use of
this API in a Python-based notebook, and believe the new API will provide the
community a convenient and powerful tool to perform pathway- and network-based
data analysis and visualization using our app in an automatic way.
PMID- 29955361
TI - Initiation, scale-up and outcomes of the Cambodian National MDR-TB programme 2006
2016: hospital and community-based treatment through an NGO-NTP partnership.
AB - Introduction: Prolonged inpatient multidrug-resistant tuberculosis (MDR-TB)
treatment for all patients is not sustainable for high-burden settings, but there
is limited information on community-based treatment programme outcomes for MDR
TB. Methods: The Cambodian Health Committee, a non-governmental organisation
(NGO), launched the Cambodian MDR-TB programme in 2006 in cooperation with the
National Tuberculosis Program (NTP) including a community-based treatment option
as a key programme component. The programme was transferred to NTP oversight in
2011 with NGO clinical management continuing. Patients electing to receive home
based treatment were followed by a dedicated adherence supporter and a
multidisciplinary outpatient team of nurses, physicians and community health
workers. Patients hospitalised for >1 month of treatment (hospital based)
received similar management after discharge. All patients received a standardised
second-line MDR-TB regimen and were provided nutritional and adherence support.
Outcomes were reviewed for patients completing 24 months of treatment and
predictors of treatment success were evaluated using logistic regression.
Results: Of 582 patients with MDR-TB who initiated treatment between September
2006 and June 2016, 20% were HIV coinfected, 288 (49%) initiated community-based
treatment and 294 (51%) received hospital-based treatment. Of 486 patients with
outcomes available, 364 (75%) were cured, 10 (2%) completed, 28 (6%) were lost to
follow-up, 3 (0.6%) failed and 77 (16%) died. There was no difference between
treatment success in community versus hospital-based groups (adjusted OR (aOR)
1.0, p=0.99). HIV infection, older age and body mass index <16 were strongly
associated with decreased treatment success (aOR 0.33, p<0.001; aOR 0.40,
p<0.001; aOR 0.40; p<0.001). Conclusions: Cambodia's NGO-NTP partnership
successfully developed and scaled up a model MDR-TB treatment programme. The
first large-scale MDR-TB programme in Asia with a significant community-based
component, the programme achieved equally high treatment success in patients with
community-based compared with hospital-based initiation of MDR treatment.
PMID- 29955362
TI - British Thoracic Society Guideline for the initial outpatient management of
pulmonary embolism.
AB - The following is a summary of the recommendations and good practice points for
the BTS Guideline for the initial outpatient management of pulmonary embolism.
Please refer to the full guideline for full information about each section.
PMID- 29955363
TI - Impact of the introduction of a universal childhood influenza vaccination
programme on influenza-related admissions to paediatric intensive care units in
England.
AB - Introduction: A universal childhood influenza vaccination programme was
introduced in the UK in September 2013. We examine the impact of the gradual
introduction of this programme on influenza-related paediatric intensive care
unit (PICU) admission rates in England. Methods: We extracted data on all
influenza-related admissions to PICUs in England in resident children aged 0-15
years old between October 2003 and March 2017 from the Paediatric Intensive Care
Audit Network (PICANet) database. We estimated influenza-associated PICU
admission rates per 100 000 children by age group, sex and winter season (October
to March), and used Poisson regression models to estimate incidence rate ratios
(IRRs) in the winter seasons since the introduction of universal childhood
vaccination compared with the two winters before the introduction of the
programme (2011-2013). Results: We identified 929 influenza-related PICU
admissions among 873 children. 48.3% of admissions were among children aged less
than 2 years old. The influenza-associated PICU admission rate was 1.32 per 100
000 children (95% CI 1.23 to 1.40). We identified a significant increase in
influenza PICU admissions in the winters following the introduction of the
universal childhood vaccination programme compared with the winters of 2010/2011
2012/2013 among children aged <5 years old: IRR 1.58 (1.05, 2.37) in children <1
year, 2.71 (1.43, 5.17) in 1 year-olds and 1.98 (1.18, 3.31) in children 2-4
years old. No significant difference was found among children aged 5-15 years.
Conclusion: The universal childhood influenza vaccination has not yet reduced the
influenza-associated burden on PICUs in England during its early phase of
introduction. Monitoring of influenza PICU admission rates needs to continue in
England to assess the long-term impact of universal paediatric influenza
vaccination. Linkage between PICANet and national infection surveillance
databases would better enable such monitoring.
PMID- 29955364
TI - Risk and temporal order of disease diagnosis of comorbidities in patients with
COPD: a population health perspective.
AB - Introduction: Comorbidities in patients with chronic obstructive pulmonary
disease (COPD) generate a major burden on healthcare. Identification of cost
effective strategies aiming at preventing and enhancing management of comorbid
conditions in patients with COPD requires deeper knowledge on epidemiological
patterns and on shared biological pathways explaining co-occurrence of diseases.
Methods: The study assesses the co-occurrence of several chronic conditions in
patients with COPD using two different datasets: Catalan Healthcare Surveillance
System (CHSS) (ES, 1.4 million registries) and Medicare (USA, 13 million
registries). Temporal order of disease diagnosis was analysed in the CHSS
dataset. Results: The results demonstrate higher prevalence of most of the
diseases, as comorbid conditions, in elderly (>65) patients with COPD compared
with non-COPD subjects, an effect observed in both CHSS and Medicare datasets.
Analysis of temporal order of disease diagnosis showed that comorbid conditions
in elderly patients with COPD tend to appear after the diagnosis of the
obstructive disease, rather than before it. Conclusion: The results provide a
population health perspective of the comorbidity challenge in patients with COPD,
indicating the increased risk of developing comorbid conditions in these
patients. The research reinforces the need for novel approaches in the prevention
and management of comorbidities in patients with COPD to effectively reduce the
overall burden of the disease on these patients.
PMID- 29955365
TI - Understanding changes in dyspnoea perception in obstructive lung disease after
mindfulness training.
AB - Introduction: Dyspnoea has been defined as a 'subjective experience of breathing
discomfort that consists of qualitatively distinct sensations that vary in
intensity'. However, the majority of available dyspnoea measures treat it as a
single entity and rely on quantitative methodology. We propose that qualitative
research can enhance our understanding of dyspnoea, in particular, how perception
varies so much among patients with similar disease states. In this paper, we
focus on how a specific type of inner attention-mindfulness-may alter perceptions
of dyspnoea. The aim is to characterise mindfulness attention, which impacts on
perceptions of dyspnoea and relate these to the multidimensional model of
dyspnoea. We explore how an individual can change their perception and therefore
relationship to similar disease states. Method: 22 patients with asthma or
chronic obstructive pulmonary disease were recruited from primary and secondary
care to an 8-week course in mindfulness-based cognitive therapy (MBCT). 12
patients took part in an in-depth qualitative interview 2 months after completing
the MBCT course. Data were recorded, transcribed and then analysed using a
framework approach, drawing on components of the multidimensional model of
dyspnoea (multidimensional dyspnoea profile, MDP). Results: We found that MBCT
training involves developing three types of mindful attention (broad attention,
informative attention and re-directive attention), which impact on perceptions of
the sensory dimension of dyspnoea. MBCT appears to target affective and sensory
perceptions articulated in the MDP model. Conclusion: More research is needed
into how mindfulness-based interventions may mediate the relationship between
affective experience and the sensory perception of dyspnoea symptoms.
PMID- 29955366
TI - Effect of three types of horseshoes and unshod feet on selected non-podal
forelimb kinematic variables measured by an extremity mounted inertial
measurement unit sensor system in sound horses at the trot under conditions of
treadmill and soft geotextile surface exercise.
AB - Therapeutic farriery is part of the management of certain orthopaedic conditions.
Non-podal parameters are important as most horses shod with therapeutic shoes are
expected to perform again and the choice of shoe type may be influenced by the
effects they may have on gait. The aim of this prospective study was to evaluate
the effects of three different shoe designs and unshod front feet on forelimb non
podal kinematic variables using an extremity mounted inertial measurement unit
(IMU) system under conditions of treadmill and overground exercise on a soft
geotextile surface at the trot. Ten sound horses with no underlying orthopaedic
problem were instrumented with eight IMUs at distal radii, tibia and third
metacarpal/tarsal regions. Measurements were performed during four consecutive
days. During the first three days, the three shoe types were randomly selected
per horse and day. On the fourth day, all horses were tested unshod. Data were
collected at the trot on a treadmill, and on a soft geotextile surface.
Specifically designed software and a proprietary algorithm processed the
accelerometer and gyroscope signals to obtain orientation and temporal data to
describe selected kinematic variables predetermined by the system. Repeated
measures analysis of variance (ANOVA) was used to assess differences between shoe
type and surface. The presence of shoes produced significant changes in
spatiotemporal variables which seemed to be related to shoe mass rather than shoe
design as there were no significant differences found between different shoe
types. Shod horses showed a gait characterised by an increased range of motion
(ROM) of the fore limbs. Previously reported effects of the investigated shoes on
podal kinematics do not seem to affect the investigated kinematic variables
indicating perhaps a compensatory effect occurring at some level in the
extremity.
PMID- 29955367
TI - Assessment of transport stress on cattle travelling a long distance (~648 km),
from Jessore (Indian border) to Chittagong, Bangladesh.
AB - The effect of long-distance transport on cattle health has not frequently been
studied in Bangladesh. The current study investigated the health conditions, and
the extent and pattern of cattle injuries, along with haemato-biochemical and
hormonal changes, before and after long-distance transportation (~648 km) from
the market of origin to the market of destination. A total of 100 adult cattle
were selected at the Benapole live cattle market, Bangladesh, for physical
examination before and after transportation. Fifty of these cattle were randomly
selected for additional haemato-biochemical evaluation just before the start of
transportation (0 hour), immediately after arrival at the destination market
(13.8+/-0.9 hours after the start of transportation) and 24 hours after arrival
at the destination market. The external health conditions and injuries were
assessed. Animals were fasting in the vehicle during transportation and provided
only with paddy straw and water before sale at the destination market. Before and
after transportation, the overall frequency of cattle injuries varied
significantly (26 per cent before v 47 per cent after transportation; P<0.001).
Cattle health conditions diverged significantly (such as nasal discharge: 15 per
cent v 28 per cent; P=0.03). The values of haemoglobin (P=0.01), total
erythrocyte count (P=0.001), total leucocyte count (P<0.001), lymphocyte
(P=0.005), neutrophil (P=0.01) and eosinophil (P=0.01) varied significantly. The
values of serum total protein (P=0.006), creatine kinase (P<0.001), triglyceride
(P=0.04), calcium (P=0.003), phosphorus (P<0.001) and alkaline phosphatase
(P=0.04) significantly differed. The overall findings indicate a high degree of
transport stress and poor animal welfare.
PMID- 29955368
TI - Immunosuppressant use and hospitalisations in adult patients with systemic lupus
erythematosus admitted to a tertiary academic medical centre.
AB - Objectives: To describe how immunosuppressant use and hospitalisation patterns
for SLE have evolved by comparing admission statistics at one academic centre
between 2005 and 2013. Methods: We identified admissions for SLE and for all
hospitalised patients by using the hospital electronic database. For adult
patients with SLE, a comprehensive chart review was conducted to identify primary
indications for hospitalisation, in-hospital mortality, mean length of stay and
immunosuppressant use. Results: The number of yearly SLE patient hospitalisations
decreased from 178 to 86 between the two times of observation. Infection was the
most common reason for hospitalisation accounting for 39.9% of hospitalisations
in 2005 versus 31.4% of hospitalisations in 2013 (p=0.29). Lupus flare accounted
for 9.6% of admissions in 2005 versus 8.1% of admissions in 2013 (p=0.72). Seven
patients died during their hospitalisation (3.9% of admissions) in 2005 as
opposed to no inpatient deaths in 2013. Of the 261 admissions between 2010 and
2013, six admissions resulted in death (2.3% of admissions). SLE patient mean
length of hospital stay decreased from 7.6 days to 6.4 days (p=0.36) compared
with all patient length of stay, which decreased from 6 days to 5.8 days.
Corticosteroid use decreased (79.8% to 61.6%, p=0.11) while hydroxychloroquine
(27.0% to 59.3%, p<0.001) use increased over time. Conclusions: The number of
hospitalisations, mortality and length of stay among hospitalised patients with
SLE decreased over time. Infection was the primary reason for inpatient
hospitalisation. Hydroxychloroquine use more than doubled over this same time
period with statistical significance. These pilot data suggest improvements in
SLE hospitalisation outcomes over time, but larger studies are needed to examine
these trends and to understand the relationship between changing medication
prescribing patterns and hospitalisation outcomes in patients with SLE.
PMID- 29955369
TI - Analysis of relationships between 25-hydroxyvitamin D, parathyroid hormone and
cathelicidin with inflammation and cardiovascular risk in subjects with
paediatric systemic lupus erythematosus: an Atherosclerosis Prevention in
Paediatric Lupus Erythematosus (APPLE) study.
AB - Objectives: Previous studies demonstrated associations between reduced serum 25
hydroxyvitamin D (25OHD), inflammation and disease activity in paediatric
systemic lupus erythematosus (pSLE). The goal of this study was to assess
parathyroid hormone (PTH) in its relationship to vitamin D and inflammation, as
well as to better understand the role of human cathelicidin (LL-37) in pSLE.
Methods: Frozen serum samples collected at baseline of the Atherosclerosis
Prevention in Paediatric Lupus Erythematosus (APPLE) study were assayed to
determine 25OHD, PTH and LL-37 levels. Pearson's correlations and Chi2 tests were
used to evaluate the relationships between 25OHD, PTH, LL-37, inflammation,
disease activity and infection using baseline values collected as part of the
APPLE study. Results: 201/221 APPLE participants had serum available for
analysis. Serum 25OHD was inversely associated with serum PTH, but not LL-37.
Serum PTH was not associated with high sensitivity C-reactive protein, carotid
intima media thickness or high-density lipoprotein (HDL) or low-density
lipoprotein (LDL) cholesterol, but was negatively associated with lipoprotein(a)
levels. Despite no association with serum 25OHD, LL-37 was negatively associated
with total cholesterol, HDL and LDL cholesterol and positively associated with
age. There was no significant difference in mean LL-37 levels in participants
with reported infection as an adverse event during the 3-year APPLE study.
Conclusions: Despite links to vitamin D levels in other studies, LL-37 levels
were not associated with baseline serum 25OHD concentrations in paediatric
patients with pSLE. Despite the lack of correlation with 25OHD, LL-37 levels in
this study were associated with cholesterol levels. Some subjects with pSLE have
significantly elevated levels of LL-37 of unknown significance. These exploratory
results addressing the role of LL-37 levels in pSLE appear worthy of future
study.
PMID- 29955371
TI - Correction: Lupus community panel proposals for optimising clinical trials: 2018.
AB - [This corrects the article DOI: 10.1136/lupus-2018-000258.].
PMID- 29955370
TI - TNF-alpha and plasma albumin as biomarkers of disease activity in systemic lupus
erythematosus.
AB - Objectives: Composite criteria/indices are presently used to diagnose and monitor
patients with systemic lupus erythematosus (SLE). Biomarkers for these purposes
would be helpful in clinical practice. We therefore evaluated a large panel of
cytokines and basic laboratory tests and investigated their performance as
discriminators versus controls and as biomarkers of disease activity (DA).
Methods: We examined 437 patients with SLE, fulfilling American College of
Rheumatology-82 criteria, and 322 matched controls. DA was assessed according to
both SLE DA Index 2000 (SLEDAI-2K) and SLE Activity Measure (SLAM). British Isles
Lupus Activity Group (BILAG) was used to assess renal DA. Additionally, 132
patients self-assessed their Global Disease Activity (PtGDA). Mesoscale Discovery
30-plex cytokine assay and routine blood chemistry was performed on fasting EDTA
plasma. Results: Of 26 tested biomarkers, we identified TNF-alpha as the superior
discriminator between patients with SLE and controls (median=4.5 pg/mL, IQR=3.1
6.2 vs median=2.3 pg/mL, IQR=2.0-2.8). The strongest correlations to SLEDAI-2K
and SLAM were obtained with TNF-alpha (Spearman rho (rho)=0.32 and rho=0.34,
respectively), partly driven by the nephritis subgroup, and with p-albumin (rho=
0.33 and rho=-0.31, respectively). P-albumin was decreased and TNF-alpha was
increased in patients with kidney involvement (renal BILAG A/B vs C/D/E, p=4*10
16 and p=6*10-9 respectively). IP-10 was increased in patients with joint
involvement (SLAM item 24>=2 vs <=1, p=0.0005) but did not differ when comparing
patients with active/inactive kidney involvement. The most powerful correlations
to PtGDA was observed with p-albumin (rho=-0.42), IL-6 (rho=0.30) and TNF-alpha
(rho=0.29). Conclusion: TNF-alpha and p-albumin both performed well as
discriminators between patients with SLE and controls and as proxies for DA
according to both rheumatologists' and patients' assessments. In particular,
renal DA was well reflected by TNF-alpha. We propose that the TNF-alpha and p
albumin merit further investigations as clinically useful biomarkers in SLE. We
also observed that the pattern of activated cytokines varies with organ
involvement.
PMID- 29955372
TI - Inconsistent anticipatory postural adjustments (APAs) in rugby players: a source
of injuries?
AB - Background: We are developing since 2010 with Thales and the Federation Francaise
de Rugby (FFR) M-Rex, a new kind of rugby scrum simulator. The study questioned
whether it could improve safety and protect players from injury by using it as a
tool for training/coaching the packs. Aim: To explore the anticipatory postural
adjustments (APAs) during the engagement of the ruck, because these predictive
neck and back muscles contractions protect the spinal cord at the time of
impacts, which is crucial to prevent injuries. Methods: We quantified the
kinematics and the EMG activities in high-level front row players during their
initial engagement, when scrummaging with M-Rex. All studies were performed with
one player interacting with the robot, at first, and then with the three players
acting together. Results: For most of the tested high-level players, the APA
latencies were highly variable from trial to trial even though the engagement
resulted in similar impacts. At time, the onset of the electromyography activity
in the neck and back muscles showed latencies inferior to 50 ms or even close to
zero prior to the impact, which rendered muscle contractions inefficient as APAs.
We were also unable to identify clear muscular synergies underlying the APAs
because of their great variability on a trial-to-trial basis. Finally, the APAs
were not related to the amplitude of the ensuing impact and were asymmetric in
most trials. All these characteristics held true, whether the player was playing
alone or with two other frontline players. Conclusion: Our result suggest that
APAs should be systematically tested in high-level rugby players as well as in
any high-level sport men at risk of neck and back injuries. Because APAs can be
efficiently trained, our study paves the way to design individual position
specific injury prevention programme.
PMID- 29955373
TI - Effects of a 12-week running programme in youth and adults with complex mood
disorders.
AB - Objective: Although numerous studies suggest a salutary effect of exercise on
mood, few studies have explored the effect of exercise in patients with complex
mental illness. Accordingly, we evaluated the impact of running on stress,
anxiety and depression in youth and adults with complex mood disorders including
comorbid diagnoses, cognitive and social impairment and high relapse rates.
Methods: Participants were members of a running group at St Joseph Healthcare
Hamilton's Mood Disorders Program, designed for clients with complex mood
disorders. On a weekly basis, participants completed Cohen's Perceived Stress
Scale, Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI)
questionnaires, providing an opportunity to evaluate the effect of running in
this population. Results: Data collected for 46 participants from April 2012 to
July 2015 indicated a significant decrease in depression (p<0.0001), anxiety
(p<0.0001) and stress (p=0.01) scores. Whereas younger participant age, younger
age at onset of illness and higher perceived levels of friendship with other
running group members (ps<=0.04) were associated with lower end-of-study
depression, anxiety and stress scores, higher attendance was associated with
decreasing BDI and BAI (ps<=0.01) scores over time. Conclusions: Aerobic exercise
in a supportive group setting may improve mood symptoms in youth and adults with
complex mood disorders, and perceived social support may be an important factor
in programme's success. Further research is required to identify specifically the
mechanisms underlying the therapeutic benefits associated with exercise-based
therapy programmes.
PMID- 29955375
TI - Prevention of sports injuries in children at school: a systematic review of
policies.
AB - Background: Participation in sports as a child improves physical and
psychological health. Schools need to promote sport while protecting against
injury. It is not clear whether increasing evidence on injury prevention
generated from professional sport is influencing school sports practices. This
study reviewed policies promoting sport safety in schools to determine whether
exposure to injury risk is recognised and whether evidence based prevention and
management are included. Methods: A search strategy to identify policies for
children aged 4-18 years was applied to electronic databases and grey literature
sources. Safeguarding policies were excluded. Included policies were critically
appraised and synthesised using modified framework analysis. Results: Twenty-six
policies were analysed. Most (57.7%) were from the USA. Ten (38.5%) focused
solely on concussion. Synthesis identified primary, secondary and tertiary injury
prevention measures relating to people (staff, students and parents), systems,
school physical environment and national-level factors. Conclusions: Robust,
evidence-based policies for reducing injury risk in school sports are limited.
Guidelines with the largest evidence base were focused on concussion, with other
school sport guidelines showing limited inclusion of evidence. Where included,
evidence focused on injury management rather than prevention and frequently
applied evidence from adult to children. Guidance was not specific to the child's
age, gender or developmental stage.
PMID- 29955374
TI - Preseason intrinsic risk factors-associated odds estimate the exposure to
proximal lower limb injury throughout the season among professional football
players.
AB - Background/aim: Football players frequently face the occurrence of non-contact
musculoskeletal injuries. The purpose of the study was to verify whether the
evaluation of combined risk factors could produce a score system to determine the
probability of injury in football players during the Brazilian football season.
Methods: Sixty-two male professional soccer players recruited from the first and
second division soccer teams, with ages between 18 and 36 years. Functional
performance evaluations were carried out at the beginning of the preseason which
included strength and jumping tests, history of injuries and characteristics of
athletes. Results and conclusions: The results were grouped and a score/monogram
was constructed.
PMID- 29955376
TI - Dysnatremia among runners in a half marathon performed under warm and humid
conditions.
AB - Background: Dysnatremia has been associated with sports activity, especially long
distance running and endurance sports. High fluid intake is associated with
hyponatremia. This study aims to evaluate dysnatremia and risk factors in half
marathon runners under warm and humid environmental conditions. Methods: A cross
sectional study was performed among randomly selected runners in the 2017 Cali
half marathon. Runners on diuretic therapy or with a known history of kidney
disease were excluded. Participants went through a 2-day assessment. Previous
medical history, training history, body mass index and running history were
determined in the first assessment. Symptoms of dysnatremia and level of fluid
consumption during the race were registered during the second assessment and post
run blood sampling for serum [Na+] was also undertaken. Results: 130 runners were
included in the study. The complete 2-day assessment was performed on 81
participants (62%) that were included in the final analysis. No cases of
hyponatremia were found; instead, there were six cases of asymptomatic
hypernatremia (7.4%). This hypernatremia had a statistically significant
association with lower frequency (p=0.01) and volume of fluid intake during the
race (water: p=0.02, Gatorade: p=0.04). Conclusion: Hyponatremia has been
associated with high fluid intake in races performed under cool weather, such as
the Boston Marathon during spring. In contrast, hypernatremia was found in a half
marathon in warm and humid weather, which was associated with lower volume and
frequency of fluid intake, suggesting that under warm and humid conditions, a
median fluid intake of 900 mL during the race could prevent this event.
PMID- 29955377
TI - Musculoskeletal examination in young athletes and non-athletes: the Finnish
Health Promoting Sports Club (FHPSC) study.
AB - Objectives: To determine the inter-rater repeatability of a musculoskeletal
examination and to compare findings between adolescent athletes and non-athletes
in Finland. Methods: In this cross-sectional study, a musculoskeletal examination
assessing posture, mobility and movement control was carried out by a sports and
exercise medicine physician on 399 athletes aged 14-17 years and 177 non
athletes. Within 2 weeks another sports and exercise medicine physician repeated
the examination for 41 adolescents to test the inter-rater repeatability.
Results: In total, 10 of the 11 tests performed had at least moderate inter-rater
reliability (kappa >=0.4 or percentage agreement >80%). Athletes more often than
non-athletes had one shoulder protruded (8.0% vs 4.0%, OR 2.81, 95% CI 1.16 to
6.81). Forty-six per cent of athletes had good knee control in the two-legged
vertical drop jump test compared with 32% of non-athletes (OR 1.99, 95% CI 1.29
to 3.06). Athletes had better core muscle control with 86.3% being able to remain
in the correct plank position for 30 s compared with 68.6% of non-athletes (OR
2.70, 95% CI 1.67 to 4.36). In the deep squat test, good lumbar spine control was
maintained only by 35.8% of athletes and 38.4% of non-athletes. Conclusion: A
basic musculoskeletal examination is sufficiently reliable to be performed by
trained physicians as a part of a periodic health evaluation. Shortfalls in
mobility, posture and movement control are common in both athletes and non
athletes. These deficits could have been caused by sedentary behaviour,
monotonous training, or both.
PMID- 29955378
TI - Fifth metatarsal stress fracture in elite male football players: an on-field
analysis of plantar loading.
AB - Objective: Evaluate plantar loading during 'on-field' common football movements
in players after fifth metatarsal (MT-5) stress fracture and compare with matched
healthy players. Methods: Fourteen elite male soccer players participated in the
study conducted on a natural grass playing surface using firm ground football
boots. Seven players who had suffered a primary stress fracture (MT-5 group) and
seven matched healthy players (controls, CON) performed three common football
movements while in-shoe plantar loading data were collected. Results: Large
between-group differences exist for maximal vertical force normalised to
bodyweight (Fmax) at the lateral toes (2-5) of the stance leg during a set-piece
kick (MT-5: 0.2+/-0.06 bodyweight (BW), CON: 0.1+/-0.05 BW, effect size (ES) 1.4)
and the curved run where the MT-5 group showed higher Fmax with very large effect
size at the lateral forefoot of the injured (closest to curve) limb when running
a curve to receive a pass (MT-5 injured-CON=0.01 BW, ES 1.5). Small between-group
differences were evident during straight-line running. However, between-limb
analysis of MT-5 group showed significant unloading of the lateral forefoot
region of the involved foot. Conclusions: Elite male football players who have
returned to play after MT-5 stress fracture display significantly higher maximum
plantar force at the lateral forefoot and lateral toes (2-5) compared with
healthy matched control players during two football movements (kick and curved
run) with the magnitude of these differences being very large. These findings may
have important implications for manipulating regional load during rehabilitation
or should a player report lateral forefoot prodromal symptoms.
PMID- 29955379
TI - PD-1/PD-L1 immune checkpoint inhibitors in advanced cervical cancer.
AB - Programmed cell death-1 and programmed cell death ligand-1 (PD-1/PD-L1) blockage
has become an important treatment modality after approval of pembrolizumab and
nivolumab by Food and Drug Administration in advanced cancers. Patients with
metastatic and recurrent cervical cancer have limited treatment options and
usually receive palliative platinum-based chemotherapy without significant
survival benefit. Recent studies provided support for usage of immune checkpoint
inhibitors in advanced cervical cancer. Around 35% of cervical squamous cell
carcinoma (C-SCC) and 17% of adenocarcinomas expressed PD-L1. Human Papilloma
Virus status was also correlated with PD-L1 expression. PD-1/PD-L1 expression in
tumor infiltrating inflammatory cells was higher in cervical cancer in comparison
to endometrial and ovarian adenocarcinomas. In C-SCC diffuse PD-L1 expression as
compared to marginal PD-L1 expression on the interface between tumor and stroma
was a risk factor for poor disease-free and disease-specific survival rates.
Higher numbers of infiltrating regulatory T cells in PD-L1 positive tumors was
associated with better prognosis. The studies performed on other cancer types
revealed PD-L1 tumor heterogeneity and transient marker expression. Drug
resistance to immune checkpoint inhibitors is also a potential problem. Currently
Phase I/II clinical trials evaluating effects of PD-1 therapy are in progress for
cervical carcinoma. Additional studies are required to develop novel biomarkers
and for standard evaluation of PD-L1 testing in order to predict response to
immune checkpoint inhibitors in all cancer types including cervical carcinoma.
PMID- 29955380
TI - Impact of tocilizumab administered intravenously or subcutaneously on patient
reported quality-of-life outcomes in patients with rheumatoid arthritis.
AB - Objective: Randomised controlled trials (RCTs) have shown tocilizumab (TCZ)
administered intravenously or subcutaneously with conventional synthetic disease
modifying antirheumatic drugs (csDMARDs) to be superior to csDMARDs alone for
improving rheumatoid arthritis (RA) disease activity. This study evaluated the
effect of TCZ-intravenous and TCZ-subcutaneous on patient-reported outcomes
(PROs) in three RCT populations. Methods: OPTION (NCT00106548), BREVACTA
(NCT01232569) and SUMMACTA (NCT01194414) were independent RCTs evaluating the
efficacy and safety of TCZ-intravenous and/or TCZ-subcutaneous with csDMARDs in
patients with RA. PROs included patient global assessment, pain, Health
Assessment Questionnaire-Disability Index, Functional Assessment of Chronic
Illness Therapy-Fatigue and Short Form-36. Study outcomes included the
proportions of patients reporting changes from baseline in PRO scores >= minimum
clinically important differences (MCID) and scores >= age and gender-matched
normative values. Results: In OPTION, more patients who received TCZ-intravenous
reported improvements in PROs >=MCID (50%-82% vs 31%-57%) and scores >= normative
values (16%-44% vs 5%-28%) at week 16 compared with placebo. Similarly, a greater
proportion of patients in BREVACTA who received TCZ-subcutaneous reported
improvements >= MCID (54%-73% vs 42%-55%) and scores >= normative values (8%-34%
vs 4%-25%) at week 12 compared with placebo. In SUMMACTA, 61%-84% of patients who
received TCZ-subcutaneous and 64%-84% of those who received TCZ-intravenous
reported improvements >= MCID and 14%-41% and 15%-24%, respectively, scores >=
normative values at week 24. Conclusions: TCZ-intravenous or TCZ-subcutaneous
with csDMARDs resulted in more patients reporting clinically meaningful
improvements and PRO scores >= normative values compared with placebo. These
improvements were similar with TCZ-intravenous and TCZ-subcutaneous.
PMID- 29955381
TI - Long-term use of adalimumab as monotherapy after attainment of low disease
activity with adalimumab plus methotrexate in patients with rheumatoid arthritis.
AB - Objective: To evaluate long-term clinical, functional and radiographic outcomes
in an open-label extension (OLE) study in patients with rheumatoid arthritis (RA)
receiving adalimumab monotherapy or adalimumab+methotrexate following attainment
of low disease activity (LDA) with adalimumab+methotrexate. Methods: Methotrexate
naive patients with early RA were randomised to adalimumab, methotrexate or
adalimumab +methotrexate in a double-blind, 2-year study. Patients who completed
the study and achieved LDA (28-joint Disease Activity Score using C reactive
protein (DAS28(CRP)<3.2) could receive adalimumab monotherapy for up to 8
additional years in the OLE; open-label methotrexate could be added per
investigator's discretion. This post hoc analysis included data up to OLE year 3
(study year 5) from patients receiving adalimumab+methotrexate who achieved LDA
at year 2 followed by adalimumab monotherapy or methotrexate reinitiation. Normal
physical function was defined as Disability Index of the Health Assessment
Questionnaire <0.5 and radiographic non-progression as change in modified total
Sharp score <=0.5. Results: Of 140 patients initiating adalimumab monotherapy, 84
(60%) received adalimumab only (methotrexate non-use) and 56 (40%) reinitiated
methotrexate (methotrexate use) during OLE treatment. Median (IQR) time to first
methotrexate use was 5.1 (0.1-31.4) weeks. Among methotrexate users, 61% retained
LDA, 48% achieved DAS28(CRP) <2.6, 45% had normal physical function and 46% had
no radiographic progression at year 5; for non-users, 63%, 50%, 58% and 50%,
respectively, achieved these milestones. Adverse event rates were similar between
methotrexate non-use and use patients. Conclusions: Adalimumab monotherapy
effectively maintained good clinical, functional and radiographic outcomes for up
to 3 additional years in >=50% of patients who attained LDA after 2 years of
adalimumab+methotrexate therapy. Trial registration number: NCT00195663; Post
results.
PMID- 29955382
TI - Prevalence of degenerative changes and overlap with spondyloarthritis-associated
lesions in the spine of patients from the DESIR cohort.
AB - Objectives: To describe the prevalence of degenerative changes on MRI and
conventional radiographs of the spine in a young population with suspicion of
axial spondyloarthritis (axSpA) and assess whether it is possible to discriminate
between degenerative changes and lesions associated with axSpA. Methods: Whole
spine MRI and cervical and lumbar radiographs of patients >=18 years with chronic
back pain (>=3 months, <=3 years, onset <50 years) were assessed for degeneration
by two readers, and for SpA lesions by two other readers, all blinded for
clinical information and results of the other readers. Degenerative scores were
adjudicated in case of disagreement (by a third reader). Patients fulfilling and
not fulfilling the Assessment of SpondyloArthritis international Society axSpA
criteria were compared for prevalence of degenerative lesions. Scores for
degenerative and SpA lesions were compared, and overlap was defined as the
presence of both types of lesions in a single vertebral unit (VU). Results: In
456/648 (70.4%) patients (46.8% men, mean age 33.6), degenerative lesions were
found with similar percentages in patients with no axSpA and with axSpA (72.4%
and 69.2%, p=0.45). Modic changes were found more often in patients with no axSpA
(29/239, 12.1%) versus patients with axSpA (19/409, 4.6%, p=0.01). Other lesions
were evenly distributed. Overlap was minimal in 19 patients (3.0%) and 32/14 674
(0.2%) VUs for SpA reader 1 and in 23 patients (3.6%) and 34/14 674 VUs (0.2%)
for SpA reader 2. Conclusion: The prevalence of degeneration is high in an early
inflammatory back pain cohort. Discrimination between degeneration and axSpA
lesions is very well possible with little overlap between degenerative and axSpA
readings.
PMID- 29955383
TI - Representativeness of a digitally engaged population and a patient organisation
population with rheumatoid arthritis and their willingness to participate in
research: a cross-sectional study.
AB - Objectives: To describe (1) the representativeness of (a) users of an online
health community (HealthUnlocked.com (HU)) with rheumatoid arthritis (RA) and (b)
paid members of an RA patient organisation, the National Rheumatoid Arthritis
Society (NRAS), compared with the general RA population; and (2) the willingness
of HU users with RA to participate in types of research (surveys, use of an app
or activity tracker, and trials). Methods: A pop-up survey was embedded on HU to
determine the characteristics of users and their willingness to participate in
research. An anonymous data set of NRAS member characteristics was provided by
the NRAS (N=2044). To represent the general RA population, characteristics of
people with RA were identified from the Clinical Practice Research Datalink
(CPRD) (N=20 594). Cross-sectional comparisons were made across the three groups.
Results: Compared with CPRD, HU respondents (n=615) were significantly younger
(49% aged below 55 years compared with 23% of CPRD patients), significantly more
deprived (21% in the most deprived Townsend quintile compared with 12% of CPRD
patients) and had more recent disease, with 62% diagnosed between 2010 and 2016
compared with 37% of CPRD patients. NRAS members were more similar to the CPRD,
but significantly under-represented those aged 75 years or over and over
represented those aged 55-75 years compared with the CPRD. High proportions of HU
users were willing to participate in future research of all types. Conclusions:
NRAS members were broadly representative of the general RA population. HU users
were younger, more deprived and more recently diagnosed. HU users were willing to
participate in most types of research.
PMID- 29955384
TI - Trends in hip fracture in patients with rheumatoid arthritis: results from the
Spanish National Inpatient Registry over a 17-year period (1999-2015). TREND-AR
study.
AB - Purpose: To analyse trends in hip fracture (HF) rates in patients with rheumatoid
arthritis (RA) over an extended time period (17 years). Methods: This
observational retrospective survey was performed by reviewing data from the
National Surveillance System for Hospital Data, which includes more than 98% of
Spanish hospitals. All hospitalisations of patients with RA and HF that were
reported from 1999 to 2015 were analysed. Codes were selected using the Ninth
International Classification of Diseases, Clinical Modification: ICD-9-CM: RA
714.0 to 714.9 and HF 820.0 to 820.3. The crude and age-adjusted incidence rate
of HF was calculated by age and sex strata over the last 17 years. General lineal
models were used to analyse trends. Results: Between 1999 and 2015, 6656 HFs
occurred in patients with RA of all ages (84.25% women, mean age 77.5 and 15.75%
men, mean age 76.37). The age-adjusted osteoporotic HF rate was 221.85/100 000 RA
persons/ year (women 227.97; men 179.06). The HF incidence rate increased yearly
by 3.1% (95% CI 2.1 to 4.0) during the 1999-2015 period (p<0.001) and was more
pronounced in men (3.5% (95% CI 2.1 to 4.9)) than in women (3.1% (95% CI 2.3 to
4.1)). The female to male ratio decreased from 1.54 in 1999 to 1.14 in 2015. The
average length of hospital stays (ALHS) decreased (p<0.001) from 16.76 days (SD
15.3) in 1999 to 10.78 days (SD 7.72) in 2015. Age at the time of hospitalisation
increased (p<0.001) from 75.3 years (SD 9.33) in 1999 to 79.92 years (SD 9.47) in
2015. There was a total of 326 (4.9%) deaths during admission, 247 (4.4%) in
women and 79 (7.5%) in men (p<0.001). Conclusion: In Spain, despite the advances
that have taken place in controlling disease activity and in treating
osteoporosis, the incidence rate of HF increased in both male and female patients
with RA.
PMID- 29955385
TI - Clinical and radiographic course of early undifferentiated arthritis under
treatment is not dependent on the number of joints with erosions at diagnosis:
results from the Swiss prospective observational cohort.
AB - Objective: To analyse whether early arthritis patients who do not fulfil the
American College of Rheumatology/European League Against Rheumatism (ACR/EULAR)
2010 classification criteria for rheumatoid arthritis (RA) have a different
course of the disease dependent on whether they can or cannot be classified as RA
because of radiographic disease (EULAR task force) at diagnosis. Methods: For
this observational study within the Swiss RA cohort SCQM, we included patients
with early undifferentiated arthritis (disease duration <=1 year), who had not
received any previous disease-modifying antirheumatic drugs (DMARDs). 2010
ACR/EULAR criteria negative patients were separated into two groups (radiographic
vs non-radiographic arthritis) depending on whether or not they had radiographic
changes defined as erosive disease by a EULAR task force (>=3 joints with
erosions). The primary outcome measure was the radiographic progression detected
employing the Ratingen erosion score. Health Assessment Questionnaire (HAQ) and
DAS-28 were used as secondary outcome measures. The average observation period
was 4 years. Results: A total of 592 patients were analysed. 240 were not
classifiable as RA by application of the 2010 ACR/EULAR criteria at baseline. In
57 patients, radiographs at the first visit were not available. 133 patients had
radiographic arthritis and 50 non-radiographic arthritis. Treatment was initiated
in all patients with DMARDs, mostly methotrexate. No differences in DAS-28 and
HAQ scores were found during follow-up. The average erosion scores were higher
among patients with initially radiographic arthritis throughout the study. The
progression of erosion scores over time, however, was higher in patients with
initially non-radiographic arthritis with less subsequent radiological
progression (3.3 erosions/year vs 0.4, respectively, p<0.0001). Conclusions: The
clinical and radiographic course of early undifferentiated arthritis under
treatment was not dependent on the presence of erosions in three or more joints
(ie, the definition of radiographic disease by the EULAR task force) at diagnosis
in our cohort.
PMID- 29955386
TI - Polymyalgia rheumatica: an autoinflammatory disorder?
PMID- 29955387
TI - MR signal intensity: staying on the bright side in MR image interpretation.
AB - In 2003, the Nobel Prize for Medicine was awarded for contribution to the
invention of MRI, reflecting the incredible value of MRI for medicine. Since
2003, enormous technical advancements have been made in acquiring MR images.
However, MRI has a complicated, accident-prone dark side; images are not
calibrated and respective images are dependent on all kinds of subjective choices
in the settings of the machine, acquisition technique parameters, reconstruction
techniques, data transmission, filtering and postprocessing techniques. The
bright side is that understanding MR techniques increases opportunities to
unravel characteristics of tissue. In this viewpoint, we summarise the different
subjective choices that can be made to generate MR images and stress the
importance of communication between radiologists and rheumatologists to correctly
interpret images.
PMID- 29955388
TI - Patient-reported outcomes (PROs) versus patient-reported outcome measures (PROMs)
Is there a difference?
PMID- 29955389
TI - The interaction among obesity, Type 2 diabetes mellitus, and periodontitis in
Vietnamese patients.
AB - To examine the relationship between obesity, Type 2 diabetes, and periodontal
disease in Vietnamese patients. The sample included 712 patients aged 18 years or
older who first visited the Institute of Traditional Medicine, Ho Chi Minh City.
All participants completed a questionnaire and underwent anthropometric index
measurements for obesity (height, weight, waist, and hip circumferences) and had
their body fat percentage measured. A full periodontal examination was performed
and a fasting glycemic level was determined. Occurrence and risk of periodontal
outcomes were compared across 3 different measurements of obesity (body mass
index, waist-hip ratio, and body fat percentage). The prevalence of periodontitis
in obese group (37.0%, 36.4%, and 24.6% by body mass index, waist-hip ratio, and
body fat percentage, respectively) or Type 2 diabetic group (50.7%) was
significantly higher than those without these conditions (p < .05). Subjects with
obesity or Type 2 diabetes had significantly greater pocket depth and clinical
attachment loss than those who are not obese or diabetic (p < .001). Multivariate
logistic regression, adjusted for confounding variables, showed that the
likelihood (odds ratio, OR) for periodontitis was highest in the obese and Type 2
diabetic group (OR = 4.24, CI [2.29, 7.86]; OR = 4.06, CI [2.24, 7.36]; and OR =
5.44, CI [2.94, 10.03]), followed by the obese and non-Type 2 diabetic group (OR
= 2.28, CI [1.05, 4.95]; OR = 2.02, CI [1.34, 3.56]), and then the nonobese and
Type 2 diabetic group (OR = 2.20, CI [1.21, 3.98]; OR = 1.99, CI [0.93, 4.24] and
OR = 5.22, CI [2.76, 9.84]) when obesity was defined by body mass index, waist
hip ratio, and body fat percentage, respectively, (p < .05). There was a
significant association between obesity, Type 2 diabetes, or those with both
systemic conditions and periodontitis in Vietnamese patients.
PMID- 29955390
TI - Influence of oral bacteria on adhesion of Streptococcus mutans and Streptococcus
sanguinis to dental materials.
AB - In this study, the effect of bacterial multispecies communities on the adhesion
of Streptococcus mutans and Streptococcus sanguinis to dental restorative
material was investigated. The saliva-coated specimens of zirconia and composite
were incubated with the following combinations: single species, S. mutans or S.
sanguinis; two species, single species combined with other oral streptococci;
multiple species, combination of Actinomyces naeslundii, Fusobacterium nucleatum,
and Prevotella ssp.; and the two-species combinations. The adherent bacteria were
counted after plating of serial dilutions. Effects of material and bacteria on
adhesion of S. mutans and S. sanguinis were evaluated with multiple linear
regression analyses. No significant differences between the materials regarding
the adhesion of S. mutans and S. sanguinis were observed. The adhesion of S.
mutans was negatively influenced by the presence of other streptococci. Enhancing
effects (610.6%) were seen in the presence of Prevotella intermedia. The adhesion
of S. sanguinis decreased in the presence of other bacteria, except F. nucleatum
(increase of 717.4%). Significant inhibitory effects were detected in the
presence of S. mutans and A. naeslundii (reduction of 95.9% and 78.5%,
respectively). The results of this study suggest that adhesion of both types of
streptococci to restorative materials is influenced by various bacterial
interactions.
PMID- 29955391
TI - Effect of ultraviolet light treatment on surface hydrophilicity and human
gingival fibroblast response on nanostructured titanium surfaces.
AB - This study was designed to investigate the effect of nanostructured TiO2 coatings
on human gingival fibroblast and to explore the influence of ultraviolet (UV)
light on surface wettability and cellular response. Ti-6Al-4V titanium alloy
discs (n = 96) were divided into three groups: a sol-gel-derived MetAliveTM (MA)
coating; hydrothermal (HT) coating; and a non-coated (NC) group. Forty-eight
titanium substrates were further treated with UV light for 15 min. The water
contact angles of the substrates were measured using the sessile drop method.
Human gingival fibroblasts were used to evaluate the cell adhesion strength and
cell proliferation on experimental surfaces. The strength of cell adhesion
against enzymatic detachment was studied after 6 hr of adhesion using gentle
trypsinization for 15 min at room temperature. A fluorescence microscope was used
for cell imaging (Zeiss-stereo-lumar-v12), and images were analyzed for cell
counting, and the percentage of detached cells were calculated. The proliferation
of cultured cells up to 10 days was determined according to the cell activity
using Alamar BlueTMassay. The HT group had the lowest contact angle value (31.1
degrees ) followed by MetAliveTM (35.3 degrees ), whereas the NC group had the
highest contact angle (50.3 degrees ). After UV light treatment, all surfaces
become considerably more hydrophilic. There was a significant difference in the
amount of adherent cells between sol-gel and HT groups when compared with the NC
group (p < .05) with detachment percentages of 35.8%, 36.4%, and 70.7%,
respectively. All substrate types showed an increase in cell proliferation rate
until 10 days. It can be concluded that nanostructured titanium oxide implant
surfaces, obtained by sol-gel and HT coating methods, enhance the surface
wettability and improve human gingival fibroblast function in terms of adhesion
and proliferation rate when compared with non-coated surfaces. UV light treatment
clearly enhances the wettability of all titanium surfaces.
PMID- 29955392
TI - Development of an assessment strategy in preclinical fixed prosthodontics course
using virtual assessment software-Part 1.
AB - The purpose of this study was to develop an assessment strategy for preclinical
foxed prosthodontics using a virtual assessment software. This descriptive study
examined 80 collected ivory teeth from previous classes prepared during
preclinical fixed prosthodontics course. Ivory teeth prepared for the complete
cast (tooth no. 46), metal ceramic (teeth nos 24 and 46), and all ceramic (tooth
no. 21) crowns were scanned and superimposed with their respective standard
preparations. Differences between these teeth and standard teeth prepared by
faculty were computed using Compare software to generate comparison percentages.
In addition, average finish line width, average total occlusal convergence,
average axial wall height, and undercut presence/absence were quantified for
student preparations using the software. Software-generated values were then
descriptively compared with faculty assessments. Comparison percentages aligned
with faculty assessments for the amount of occlusal/incisal reduction and finish
line location. The average axial wall height and finish line width calculated by
Compare software were grouped based on their respective faculty assessment
criteria. Software-generated comparison percentages may be used to assess the
amount of occlusal/incisal reduction and finish line location in student
preparations. Additionally, averages extracted from Compare software could be
used to assess student performance for axial wall height and finish line width.
PMID- 29955393
TI - Development of an assessment strategy in preclinical fixed prosthodontics course
using virtual assessment software-Part 2.
AB - The purpose of this study was to evaluate interrater agreement between faculty
and virtual assessments of preparations for complete coverage restorations in
preclinical fixed prosthodontics. Teeth prepared during preclinical fixed
prosthodontics practical exams at the University at Buffalo School of Dental
Medicine were used in this study. Teeth were prepared for fabrication of complete
cast, metal ceramic, and all ceramic crowns. The specimens were digitized using
an intraoral scanner. Then, they were virtually superimposed on the corresponding
standard preparations using Compare software. The software was used to quantify
comparison percentages, average finish line widths, and average axial wall
heights. Two calibrated faculty members assessed preparations for
occlusal/incisal reduction, finish line location, axial wall height, and finish
line width using traditional assessment forms. Cohen's kappa coefficient was used
to measure interrater agreement between faculty and virtual assessments. Kappa
interrater agreement scores ranged between 0.83 and 0.88 for virtually assessed
comparison percentages and sums of faculty-assessed occlusal/incisal reduction
and finish line location. Kappa interrater agreement score ranges were 0.64-0.94
and 0.74-0.89 for comparisons of virtual and faculty assessments for axial wall
height and finish line width, respectively. Virtual assessments are similar to
faculty assessments for occlusal/incisal reduction, finish line location, axial
wall height, and finish line width in fixed prosthodontics and can be used as
equivalent evaluations of student performance for these criteria.
PMID- 29955394
TI - Choroidal Thickness in Chinese Children Aged 8 to 11 Years with Mild and Moderate
Myopia.
AB - Purpose: To investigate macular choroidal thickness (CT), topographical
variation, and associations between subfoveal choroidal thickness (SFCT) and age,
gender, spherical equivalent (SE), and axial length (AL) in Chinese healthy mild
and moderate myopia children aged 8 to 11 years. Methods: One hundred twenty eyes
from 120 healthy children were studied. Children were divided into mild and
moderate myopia groups. AL and CT were evaluated. CTs were measured at the fovea,
and 1 mm, 2 mm, and 3 mm nasal, temporal, superior, and inferior to the fovea.
Results: SFCT was 252.80 +/- 46.95 um in the whole population. AL was shorter in
the mild myopia group (24.18 +/- 0.69 mm) than in the moderate myopia group
(24.97 +/- 0.68 mm, P < 0.001), and SFCT was thicker in the mild myopia group
(262.00 +/- 40.57 um) than in the moderate myopia group (236.00 +/- 55.08 um,
P=0.005). The topographical variation was similar in refraction groups. CTs nasal
to the fovea thinned gradually and were all significantly thinner than SFCT. CTs
in the other three directions gradually thickened and peaked at locations of 2 mm
to the fovea. Then, CTs thinned at 3 mm to the fovea. The thickest choroid is
located temporal to the fovea. There were significant negative correlations
between AL and SFCT in the mild myopia group and the whole population. No other
correlations were found. Conclusions: The topographical variations of choroidal
thickness were similar in mild and moderate myopia groups with the thickest
locations temporal to the fovea. SFCT was relatively stable in children in narrow
range of age and refractive error.
PMID- 29955395
TI - Changes in Hysterectomy Route and Adnexal Removal for Benign Disease in Australia
2001-2015: A National Population-Based Study.
AB - Objective: Hysterectomy rates have fallen over recent years and there remains
debate whether salpingectomy should be performed to reduce the lifetime risk of
ovarian cancer. We examined trends in adnexal removal and route of hysterectomy
in Australia between 2001 and 2015. Methods: Data were obtained from the national
procedural dataset for hysterectomy approach (vaginal, VH; abdominal, AH; and,
laparoscopic, LH) and rates of adnexal removal, as well as endometrial ablation.
The total female population in two age groups ("younger age group," 35 to 54
years, and "older age group," 55 to 74 years) was obtained from the Australian
Bureau of Statistics. Results: The rate of hysterectomy fell in both younger
(61.7 versus 45.2/10000/year, p < 0.005) and older (38.8 versus 33.2/10000/year,
p < 0.005) age groups. In both age groups there were significant decreases in the
incidence rates for VH (by 53% in the younger age group and 29% in the older age
group) and AH (by 53% and 55%, respectively). The rates of LH increased by 153%
in the younger age group and 307% in the older age group. Overall, the proportion
of hysterectomies involving adnexal removal increased (31% versus 65% in the
younger age group, p < 0.005; 44% versus 58% in the older age group, p < 0.005).
The increase occurred almost entirely after 2011. Conclusion: Hysterectomy is
becoming less common, and both vaginal and abdominal hysterectomy are being
replaced by laparoscopic hysterectomy. Removal of the adnexae is now more common
in younger women.
PMID- 29955396
TI - Treatment of Aortic and Iliac Artery Aneurysms with Multilayer Flow Modulator:
Single Centre Experiences.
AB - Objective: Presenting early and midterm results of aortic and iliac artery
aneurysms treated with Multilayer Flow Modulators (MFM). Methods: We
retrospectively reviewed the medical records of 23 patients (19 males and 4
females) who are admitted to our clinic between April of 2014 and February of
2016, diagnosed with thoracoabdominal aortic aneurysm and/or iliac aneurysm, and
treated using MFM. The patients were followed up for the development of potential
clinical presentations for 12 months. Results: MFM implantation was successfully
completed in all the patients. During the process, two patients developed
endoleak and so they were treated with postdilatation that was performed through
balloon intervention, whereby the patients fully recovered. Although a short-term
ischemic cerebrovascular event occurred in one of the patients 36 hours after the
MFM, the patient recuperated without any noticeable neurological sequelae.
Overall, three patients died after the procedure, one of whom died in hospital
three days following the intervention due to acute renal failure, while the
second one lost his life at the end of the first month due to the occlusion of
superior mesenteric and celiac arteries. The third patient died at the end of the
third month due to acute myocardial infarction. The rest of the patients
developed no complications or had no mortality at their 12-month follow-ups.
Conclusion: MFM can be preferred as an alternative approach in the treatment of
aorta and iliac artery aneurysms including major lateral branches. The present
results should be confirmed with additional future studies conducted with larger
patient groups for longer periods.
PMID- 29955397
TI - BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia
Cells and Synergises with Daunorubicin in Causing Cell Death.
AB - S100A8 and S100A9 are both members of the S100 family and have been shown to play
roles in myeloid differentiation, autophagy, apoptosis, and chemotherapy
resistance. In this study we demonstrate that the BET-bromodomain inhibitor JQ1
causes rapid suppression of S100A8 and S100A9 mRNA and protein in a reversible
manner. In addition, we show that JQ1 synergises with daunorubicin in causing AML
cell death. Daunorubicin alone causes a dose- and time-dependent increase in
S100A8 and S100A9 protein levels in AML cell lines which is overcome by
cotreatment with JQ1. This suggests that JQ1 synergises with daunorubicin in
causing apoptosis via suppression of S100A8 and S100A9 levels.
PMID- 29955398
TI - A Complex Cardiac Mass Originating from Interatrial Septum in a Patient with
History of Kidney Cancer: A Case Report and Literature Review.
AB - Cardiac tumors are a rare phenomenon, and most cases are secondary to metastatic
cancers rather than primary tumors. Renal cell carcinoma (RCC) is notorious for
metastasis to cardiac tissue. Tumor thrombus migration to the renal vein and
inferior vena cava happens in up to 10% of patients with RCC. Transitional cell
carcinomas are another form of renal cancer, which may metastasize to the heart
and are associated with widespread metastasis. Here, we report a patient with a
past medical history of metastatic transitional cell cancer of renal pelvis under
treatment with checkpoint inhibitor therapy presenting with shortness of breath.
He had disseminated metastasis to bones, pleural space, lungs, and muscles. A
large mass was found in the interatrial septum with invasion to the right and
left atrium. The mass had a cystic component protruding into the left atrium. He
passed away a few days after presentation.
PMID- 29955399
TI - Successful Treatment of Actinic Keratosis with Kanuka Honey.
AB - Actinic keratoses form as rough, scaly plaques on sun-exposed areas; they can be
an important step in premalignant progression to squamous cell cancer of the
skin. Currently, pharmacological treatments consist of topical immunomodulatory
agents with poor side effect profiles. Use of honey has been common in both
ancient and modern medicine, where it is now a key therapy in the management of
wound healing. In vitro studies show the New Zealand native Kanuka honey to have
immunomodulatory and antimitotic effects, with recent evidence suggesting
efficacy of topical application in a variety of dermatological contexts,
including rosacea and psoriasis. Here, we present a case report of a 66-year-old
gentleman with an actinic keratosis on his hand, which had been present for
years. Regular application of Kanuka honey over three months resulted in
remission immediately following the treatment period with no signs of recurrence
at nine months.
PMID- 29955400
TI - Anti-PD-1 Therapy-Associated Perforating Colitis.
AB - Inhibition of immune checkpoint T cell regulatory molecules by using programmed
cell death protein 1 (PD-1), or its ligand (PDL-1), and cytotoxic T-lymphocyte
associated antigen 4 (CTLA-4) has been increasingly used to treat advanced
malignancies. The immune-related adverse effects associated with these treatments
such as diarrhea, colitis, and CTLA-4 treatment-associated perforating colitis
have been reported. However, anti-PD-1/PD-L1-associated perforating colitis has
rarely been reported. We report a case of colonic perforation in a patient
recently treated with pembrolizumab, a PD-1 inhibitor for metastatic melanoma.
Awareness of anti-PD-1/PD-L1-associated colitis and perforation will facilitate a
timely diagnosis and management as they are increasingly used in oncology.
PMID- 29955401
TI - Endoscopic and Pathologic Resolution of Chronic Nonsteroidal Anti-Inflammatory
Drug-Induced Diaphragm-Like Colonic Strictures and Ulceration.
AB - The chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) has steadily
increased and, as a result, adverse effects have become more common. Isolated
case reports have documented diaphragm-like colonic strictures and ulceration as
the result of NSAID use. We report a unique case of this rare side effect with
documented endoscopic and histologic healing of multiple proximal diaphragm-like
colonic strictures and ulceration months after simple discontinuation of NSAID
therapy.
PMID- 29955402
TI - Hepatic Iron Overload following Liver Transplantation from a C282Y/H63D Compound
Heterozygous Donor.
AB - Hereditary hemochromatosis (HH) is a genetic disease associated with progressive
iron overload, eventually leading in some cases to damage of parenchymal organs,
such as the liver, pancreas, and heart. Although the gene had been identified
(HFE), HH pathogenesis remains to be fully elucidated. We report here, for the
first time, a case of inadvertent transplantation of a liver from a donor with
C282Y/H63D compound heterozygosity into a nonhemochromatotic 19-year-old
Caucasian male recipient with primary sclerosing cholangitis. Progressive iron
overload occurred over 1.5 years, as observed in liver biopsies and iron studies,
after ruling out secondary causes of iron overload. This case strengthens the
hypothesis that the liver, rather than the small intestine, plays a primary role
in the maintenance of iron homeostasis.
PMID- 29955403
TI - Parkinsonism Associated with Pathological 123I-FP-CIT SPECT (DaTSCAN) Results as
the Initial Manifestation of Sporadic Creutzfeldt-Jakob Disease.
AB - Sporadic Creutzfeldt-Jakob disease (sCJD) is a type of progressive, subacute
encephalopathy associated with spongiform degeneration of the central nervous
system. sCJD includes a broad and heterogeneous spectrum of clinical variants,
but extrapyramidal symptoms and signs at disease onset were rarely reported. We
describe a case of unilateral parkinsonism associated with pathological 123I
ioflupane SPECT (DaTSCAN) results as the initial manifestation of M129V subtype
sCJD patient. To the best of our knowledge, only 2 cases of Creutzfeldt-Jakob
disease demonstrating nigrostriatal dopaminergic deficits in vivo using DaTSCAN
have been published in the literature.
PMID- 29955404
TI - Neck-Tongue Syndrome: Viewpoints on Etiology in a Patient with Bilateral
Symptoms.
AB - Neck-Tongue Syndrome is a rare entity, and when it presents in the pediatric age
group, it is usually due to osseous, ligamentous, or nervous anatomic variation.
We present below a case involving a patient whose bilateral symptoms were
intermittently present from the age of five to the age of twenty-one years and
discuss this case in light of the present theories of the anatomic substrate
underlying this syndrome.
PMID- 29955405
TI - Limb Pain as Unusual Presentation of a Parietal Intraparenchymal Bleeding
Associated with Crack Cocaine Use: A Case Report.
AB - Limb pain as a presenting feature of an ischemic or hemorrhagic stroke is
extremely rare. Here we present a case of a 65-year-old male with complaints of
left arm pain and allodynia (specifically light touch to any part of the left arm
produced significant discomfort) who was found to have a right parietal lobe
intraparenchymal bleed after smoking crack cocaine. Acute central pain is mainly
associated with parietal, thalamic, and brainstem lesions. It has been proposed
that acute limb pain from a parietal lobe stroke is due to the disconnection of
the parietal cortex from the thalamus secondary to the interruption of the
pathways between the hemisphere and thalamus/basal ganglia.
PMID- 29955406
TI - Placenta Accreta following Hysteroscopic Lysis of Adhesions Caused by Asherman's
Syndrome: A Case Report and Literature Review.
AB - Asherman's syndrome is defined as partial or complete obstruction of the uterine
cavity primarily caused by intrauterine procedures and infections. Hysteroscopic
adhesiolysis is commonly used to treat Asherman's syndrome. Although the
frequency of placenta accreta is known to increase with pregnancy after
hysteroscopic adhesiolysis, precise data remain unknown. We report a case of
placenta accreta following hysteroscopic lysis of adhesions caused by Asherman's
syndrome and IVF treatment and review the literature on placenta accreta
following hysteroscopic adhesiolysis. It is necessary to consider placenta
accreta as a complication of pregnancies after hysteroscopic adhesiolysis for
Asherman's syndrome, particularly in those conceived using IVF.
PMID- 29955407
TI - EGFR T790M-Positive Lung Adenocarcinoma Metastases to the Pituitary Gland Causing
Adrenal Insufficiency: A Case Report.
AB - A 64-year-old man, with history of micropapillary thyroid cancer and epidermal
growth factor receptor-positive lung adenocarcinoma with no evidence of active
disease for 3 years after chemotherapy and radiation on erlotinib, presented with
fatigue, nausea, lack of appetite, and xeroderma. A screening magnetic resonance
image of the patient's head demonstrated a new bilateral pituitary mass. Initial
evaluation revealed low morning cortisol, and the patient was diagnosed with
adrenal insufficiency. His symptoms rapidly improved with maintenance
glucocorticoids. Soon thereafter, the patient developed an acute visual deficit
secondary to enlargement of the pituitary mass, and biopsy revealed EGFR T790M
positive metastatic lung adenocarcinoma. Hence, we present a rare case of
metastatic lung adenocarcinoma to the pituitary causing secondary adrenal
insufficiency.
PMID- 29955409
TI - Neurotrophic Keratopathy after Trigeminal Nerve Block for Treatment of
Postherpetic Neuralgia.
AB - Purpose: To report a case of persistent corneal epithelial defect that had
occurred after a trigeminal nerve block. Case Presentation: A 75-year-old female
had suffered from postherpetic neuralgia for 8 years. She underwent Gasserian
ganglion block surgery and noticed declining visual acuity in the right eye on
the following day. She presented with severe hyperemia and corneal epithelial
defects in the right eye and experienced remarkable reduction of sensitivity in
the right cornea. She was diagnosed with neurotrophic keratopathy. Ofloxacin eye
ointment and rebamipide ophthalmic suspension ameliorated the corneal epithelial
defects but superficial punctate keratopathy, corneal superficial
neovascularization, and Descemet's fold persisted. Although the epithelial
defects occasionally recurred, the corneal sensation and epithelial defects,
Descemet's fold, and corneal superficial neovascularization all improved around 5
months after trigeminal nerve block. The HRT II Rostock Cornea Module (RCM) could
not detect any corneal subbasal nerve fibers at postoperative 4 months; however,
it could detect them at postoperative 6 months. Conclusions: As the nerve block
effect wore off, the corneal subbasal nerve fibers slowly regenerated. As the
corneal sensation improved, the corneal epithelial defects and superficial
neovascularization also improved. The HRT II RCM appeared useful for observing
loss and regeneration of the corneal subbasal nerve fibers.
PMID- 29955408
TI - Metastatic Melanoma of Uncertain Primary with 5-Year Durable Response after
Conventional Therapy: A Case Report with Literature Review.
AB - A 51-year-old Thai woman presented with bilateral leg edema and painful left
inguinal mass for 6 months. Physical examination revealed matted bilateral
inguinal lymph nodes up to 9 cm in size. Otherwise, physical examinations
including skin were unremarkable. The result of the lymph node incisional biopsy
is consistent with that of metastatic melanoma. The extensive investigation
demonstrated multiple intra-abdominal and inguinal lymph nodes without detectable
primary tumor. Palliative radiation and conventional chemotherapy were
prescribed. The CT scan between treatments showed that the response was stable
disease, but the following CT scan demonstrated a gradual decrease in size from
August 2012 to November 2017 including the lesions outside radiation fields.
Moreover, she developed vitiligo during a follow-up visit. The previous data
reported the median overall survival among the patients who were treated with
conventional chemotherapy ranging from 9.1 to 9.3 months and whose 5-year
survival was less than 10%. This case represented a metastatic melanoma of
unknown primary who achieved a durable response by conventional treatment. The
clinical features including nodal-only disease, vitiligo, and abscopal effect of
radiation were considered to be the favorable factors.
PMID- 29955410
TI - Successful Removal of a Chronic Aspirated Foreign Body after Twelve Years.
AB - Chronic retention of aspirated foreign bodies is rare but can result in indolent
systemic and respiratory symptoms. Bronchoscopy may show features of tissue
reaction to the foreign body, including granulation tissue, endobronchial
stenosis, strictures, edema, and airway distortion. The diagnosis of foreign body
aspiration is often difficult to establish since some patients may not give a
clear history of aspiration or may present late. In addition, patients may be
misdiagnosed with chronic pneumonia, bronchitis, asthma, or malignancy. We
present the case of a 42-year-old male who had a chronically retained piece of an
aluminum beverage container in the left mainstem bronchus for 12 years. Careful
history, radiographic evaluation, and bronchoscopic examination revealed the
foreign body, which was successfully extracted by rigid bronchoscopy.
PMID- 29955411
TI - De Novo Postinfectious Glomerulonephritis Secondary to Nephritogenic Streptococci
as the Cause of Transplant Acute Kidney Injury: A Case Report and Review of the
Literature.
AB - Acute kidney injury is common among kidney transplant recipients. Postinfectious
glomerulonephritis secondary to nephritogenic streptococci is one of the oldest
known etiologies of acute kidney injury in native kidneys but rarely reported
among kidney transplant recipients. This report is of a biopsy-proven case of
acute kidney injury in a renal allograft recipient caused by de novo
poststreptococcal glomerulonephritis.
PMID- 29955412
TI - Bladder Rupture as a Complication of Circumcision following Total Subcoronal
Urethral Ligation.
AB - Circumcision is one of the most commonly performed procedures and generally is
considered a safe and minor surgery. However, serious and catastrophic
complications may sometime occur if adequate attention is not paid to all aspects
of this procedure. Bleeding is the most common early complication of circumcision
and sometimes is controlled by applying sutures. We hereby report a case of
urethral obstruction after deep suturing of the bleeding site performed at a
district center that led to bladder rupture as an exceedingly rare complication
following circumcision.
PMID- 29955413
TI - Extraction of Unerupted Maxillary Canine Teeth in a Maned Wolf (Chrysocyon
brachyurus).
AB - The purpose of this case report is to describe the diagnosis and treatment of
unerupted canine teeth in a maned wolf. After physical examination, complete
blood count, and serum biochemical profile, the animal underwent general
anesthesia and head radiography was performed to confirm the diagnosis. The
treatment consisted of the extraction of both maxillary canine teeth and clinical
and radiographic follow-up of the right mandibular canine tooth.
PMID- 29955414
TI - Cutaneous Disease as Sole Clinical Manifestation of Protothecosis in a Boxer Dog.
AB - Prototheca wickerhamii is ubiquitous, saprophytic achlorophyllous algae that
cause opportunistic infections in the dog and cat and disseminated disease
usually in immunocompromised animals. In this report an uncommon case of canine
cutaneous protothecosis is presented. A 6-year-old female boxer was brought in
with skin lesions that consisted of nodules and generalized footpad
hyperkeratosis, depigmentation, and erosion. Cytology and histopathology showed
pyogranulomatous inflammation along with organisms containing round sporangia
with spherical sporangiospores. PCR and sequencing identified the causal organism
as Prototheca wickerhamii. Therapy applied in this patient with either
fluconazole alone or combination of amphotericin B and itraconazole proved
effective only for footpad lesions but not for skin nodules. Systemic therapy
seems to be ineffective for skin nodules, at least in chronic cases of canine
cutaneous protothecosis. Although canine protothecosis usually presents with the
disseminated form, cutaneous disease as sole clinical manifestation of the
infection may also be witnessed.
PMID- 29955415
TI - Pedicled Instep Flap and Tibial Nerve Reconstruction in a Cynomolgus Monkey
[Macaca fascicularis].
AB - A male cynomolgus monkey experienced extensive soft tissue trauma to the right
caudal calf area. Some weeks after complete healing of the original wounds, the
monkey developed a chronic pressure sore on plantar surface of the heel of its
right foot. A loss of sensitivity in the sole of the foot was hypothesized. The
skin defect was closed by a medial sensate pedicled instep flap followed by
counter transplantation of a full thickness graft from the interdigital webspace.
The integrity of the tibial nerve was revised and reconstructed by means of the
turnover flap technique. Both procedures were successful. This is an uncommon
case in an exotic veterinary patient as it demonstrates a reconstructive skin
flap procedure for the treatment of a chronic, denervated wound in combination
with the successful reconstruction of 2.5 cm gap in the tibial nerve.
PMID- 29955416
TI - Common Arterial Trunk in a 3-Day-Old Alpaca Cria.
AB - A 3-day-old alpaca cria presented for progressive weakness and dyspnea since
birth. Complete bloodwork, thoracic radiographs, and endoscopic examination of
the nasal passages and distal trachea revealed no significant findings.
Echocardiogram and contrast study revealed a single artery overriding a large
ventricular septal defect (VSD). A small atrial septal defect or patent foramen
ovale was also noted. Color flow Doppler and an agitated saline contrast study
revealed bidirectional but primarily right to left flow through the VSD and
bidirectional shunting through the atrial defect. Differential diagnosis based on
echocardiographic findings included common arterial trunk, Tetralogy of Fallot,
and pulmonary atresia with a VSD. Postmortem examination revealed a large common
arterial trunk with a quadricuspid valve overriding a VSD. Additionally, defect
in the atrial septum was determined to be a patent foramen ovale. A single
pulmonary trunk arose from the common arterial trunk and bifurcated to the left
and right pulmonary artery, consistent with a Collet and Edwards' type I common
arterial trunk with aortic predominance. Although uncommon, congenital cardiac
defects should be considered in animals presenting with clinical signs of
hypoxemia, dyspnea, or failure to thrive.
PMID- 29955417
TI - Oestrus ovis L. (Diptera: Oestridae) Induced Nasal Myiasis in a Dog from Northern
Italy.
AB - A companion dog from Milan province (northern Italy), presenting with frequent
and violent sneezing, underwent rhinoscopy, laryngoscopy, and tracheoscopy
procedures. During rhinoscopy, a dipteran larva was isolated from the dog and
identified as first instar larval stage of O. ovis by morphological features.
Reports of O. ovis in domestic carnivores are sporadic and nevertheless this
infestion should be considered as a possible differential diagnosis of rhinitis
in domestic carnivores living in contaminated areas by the fly as consequence of
the presence of sheep and goats. This report described a case of autochthonous
infestion in a dog from an area where O. ovis was not historically present but it
could be affected by a possible expansion of the fly as a consequence of climate
change. This is the first record of Oestrus ovis infestion in a dog in Italy and,
at the same time, the most northerly finding of larvae of sheep bot fly in the
country.
PMID- 29955418
TI - Coinfection with Tritrichomonas foetus and Giardia duodenalis in Two Cats with
Chronic Diarrhea.
AB - A Tritrichomonas foetus and Giardia duodenalis mixed infection was diagnosed in
two Maine Coon cats aged six months. One of them presented a history of chronic
liquid diarrhea and of several unsuccessful treatments. In both cats, G.
duodenalis and trichomonads were detected in fecal smears from freshly voided
feces; the presence of T. foetus was confirmed by a real-time PCR assay. The cats
completely recovered after treatment with ronidazole. In a refrigerated fecal
sample collected from the cat with chronic diarrhea, drop-shaped trichomonad
pseudocysts smaller than G. duodenalis cysts were detected. They appeared
brownish or light-bluish when stained with Lugol's solution or with Giemsa stain,
respectively, and their morphological features were similar to those expressed by
bovine T. foetus pseudocysts in vitro. Existence of pseudocysts even in feline
trichomonads is noteworthy as they could represent a form of protozoan resistance
due to unfavorable conditions whose detection in refrigerated feces can be a
useful clue for clinicians.
PMID- 29955419
TI - Penile Urethral Hypospadias with Two Fistulae and Diverticulum in a Saanen Kid.
AB - Hypospadias is a rare congenital defect reported in most animal species and
humans. This case study reports a hypospadiac case in a goat kid with urethral
diverticulum diagnosed in Sudan for the first time. A 45-day-old male kid was
presented to the Veterinary Teaching Hospital, College of Veterinary Medicine,
Sudan University of Science and Technology (SUST), with a history of an
increasing prescrotal swelling. At presentation in the clinic the kid was bright
and alert and the vital parameters were within the normal physiological range.
Ultrasonography was performed to assess the integrity of the urinary system using
(3.5-5) MHz curvilinear probe and it revealed normal kidneys and a distended
urinary bladder. The kid was referred to surgery and two hypospadiac urinary
fistulae were found. One fistula was sutured and the other was not corrected due
to catheterization failure.
PMID- 29955420
TI - Case Report of Bilateral 3-4 Metatarsal Syndactyly in a Pet Rabbit.
AB - We report the first case of spontaneous syndactyly reported in a pet rabbit.
Syndactyly only caused an atypical gait in the rabbit. The radiological study
revealed bilateral 3rd and 4th metatarsal bones fused in its entire length
preserving normal joint surfaces resembling syndactyly type Ia. The cause of this
congenital malformation was unknown.
PMID- 29955421
TI - Long-Term Outcome of En Bloc Extensive Resection of the Penis and Prepuce
Associated with a Permanent Perineal Urethrostomy in a Gelding Affected by
Squamous Cell Carcinoma.
AB - A 15-year-old gelding was referred for a florid, cauliflower-like ulcerated mass,
enclosing penis and prepuce together with penile urethra showing a malodorous
purulent and blood-stained discharge and larvae infestation. En bloc extensive
resection of the penis and prepuce, without penile retroversion or pexy to
ventral abdomen associated with a permanent perineal urethrostomy, was performed.
Histology of the mass revealed a squamous cell carcinoma of penis and prepuce.
The surgical technique that was adopted is a modified version of that already
described that allows a more proximal resection of the penile body and is a valid
option for treating advanced SCC lesions involving the penis. Early postsurgical
complications (mild strangury, haemorrhage from the urethrostomy site and its
partial dehiscence, and infection of the abdominal wound) were managed with a
medical treatment and resolved within 5 to 12 days. Three years after surgery the
horse is in good body condition and does not show any sign of recurrence or
disorders related to the surgery.
PMID- 29955422
TI - Benign Pigmented Dermal Basal Cell Tumor in a Namibian Cheetah (Acinonyx
jubatus).
AB - A 3.5-year-old wild born cheetah (Acinonyx jubatus), living in a large enclosure
on a private Namibian farm, developed a large exophytic nodular neoplasm in its
skin at the height of the left shoulder blade. We describe the clinical
appearance, the surgical removal, and histological examination of the tumor,
which was diagnosed as a moderately pigmented benign basal cell tumor. A three
year follow-up showed no evidence of recurrence after the surgery. Although
neoplasia is reported in nondomestic felids, only very few concern cheetahs. So
far, no case of basal cell tumor was described in this species.
PMID- 29955423
TI - Perineal Protrusion Secondary to Imperforate Hymen and Hydrocolpos in an 8-Year
Old Spayed Female Dog.
AB - An 8-year-old female spayed Dachshund presented with an acute onset of dysuria,
dyschezia, and painful perineal protrusion. A perineal hernia was ruled out on
digital rectal examination, and blood work was unremarkable. An extremely dilated
vagina was identified on computed tomography, and hydrocolpos was suspected.
Endoscopic vaginal exam confirmed the diagnosis of imperforate hymen. The
membrane was ruptured digitally and remnants were removed endoscopically,
resulting in resolution of clinical signs. Imperforate hymen is a rare congenital
abnormality that can result in extensive fluid accumulation within the vagina and
subsequent compression of local structures or secondary infection. Treatment of
hydrocolpos includes membrane perforation and removal.
PMID- 29955424
TI - Hiccup-Like Response in a Dog Anesthetized with Isoflurane.
AB - An eight-year-old, female intact Golden Retriever underwent magnetic resonance
imaging (MRI) for investigation of urinary and faecal incontinence. Soon after
induction of general anesthesia, tracheal intubation, and isoflurane
administration, hiccup-like movements were evident. These hiccup-like movements
did not respond to hyperventilation and increase of anesthetic. After having
ruled out pulmonary disease, the animal was reanesthetized with a similar
technique; hiccup-like movements reoccurred and did not stop after
discontinuation of isoflurane and commencement of a propofol infusion.
Eventually, a nondepolarizing neuromuscular blocking agent was administered to
stop the hiccup-like response and allow MRI to be performed. This case report
describes the pathophysiology of hiccup-like response and its management in a
dog.
PMID- 29955425
TI - Mycobacterium tuberculosis and Dual M. tuberculosis/M. bovis Infection as the
Cause of Tuberculosis in a Gorilla and a Lioness, Respectively, in Ibadan Zoo,
Nigeria.
AB - Tuberculosis (TB) in zoo animals is an important public health problem in places
where it occurs. This is even very important in countries where there is little
public health awareness about the disease; thus confined animals in the zoo can
be infected directly or indirectly by infected humans and vice versa. In Nigeria,
the problem of TB is a major concern among both humans and cattle. Here, we
present cases of Mycobacterium tuberculosis and M. tuberculosis/M. bovis
infections in a female gorilla and a lioness, respectively, in a zoo in Ibadan,
Nigeria. These cases were confirmed after bacteriological examinations and DNA
from granulomatous lesions of the animals' carcasses were subjected to the Hain
and spoligotyping techniques. Our findings reveal the first documented report of
TB infections in a gorilla and a lioness in zoo animals in Nigeria. The public
health risks of tuberculosis in zoological settings are therefore reemphasized.
PMID- 29955426
TI - Case Report of a Satin Guinea Pig with Fibrous Osteodystrophy That Resembles
Human Pseudohypoparathyroidism.
AB - A case report of a 2-year-old female satin guinea pig with a history of dental
overgrowth and lameness and radiological lesions of fibrous osteodystrophy is
presented. The most relevant clinical findings were bone demineralization, high
level of parathyroid hormone (PTH), normophosphatemia, normal ionized calcium,
and low total thyroxine (tT4) with a normal renal function. Long-term treatment
was based on teeth coronal reduction and maintaining a balanced diet. PTH
measurement was performed with a kit suitable for rats to test 4 different paired
samples of guinea pigs and resulted in similar results for each pair of
measurements. Two kits routinely employed in dogs and cats failed in measuring
PTH in guinea pig serum samples. The ionized calcium, PTH, and tT4 values, not
previously reported in similar cases, were obtained. The determination of tT4
could be useful in the diagnosis of fibrous osteodystrophy in guinea pigs. The
observed findings show similarity with human pseudohypoparathyroidism type Ia, a
disease caused by an inactivating heterozygous mutation of the stimulatory G
protein alpha subunit from the maternal genome that induces multiple hormone
resistance and that courses with a syndrome called Albright hereditary
osteodystrophy. Naturally occurring pseudohypoparathyroidism in animals has been
reported previously only in a ferret.
PMID- 29955427
TI - Treatment of an Esophageal Stricture in a 1-Month-Old Miniature Shetland Colt.
AB - A 1-month-old Miniature Shetland colt was presented to the Burg Muggenhausen
Equine Clinic. Primary complaints were regurgitation of milk, bilateral white
nasal discharge, and weakness. Physical examination, endoscopy of the esophagus,
and contrast radiography led to the diagnosis of an esophageal stricture and
aspiration pneumonia. Surgical treatment by means of an esophagomyotomy was
performed. The foal improved only temporarily and multiple sessions of endoscopic
balloon dilation of the esophagus were performed afterwards. 12 months after the
final treatment the foal was healthy and had no complaints regarding esophageal
function.
PMID- 29955428
TI - Gastric Intussusceptions in a Red Corn Snake (Pantherophis guttatus) Associated
with Cryptosporidiosis.
AB - A 3-year-old female red corn snake (Pantherophis guttatus) was presented for a
three-week history of anorexia and decreased defecations. On physical
examination, a soft midbody intracoelomic swelling was palpated. Transcutaneous
coelomic ultrasound revealed a target-like mass on a transverse section of the
stomach, suggesting the presence of a gastrointestinal intussusception. On
exploratory coeliotomy, a double compounded esophagogastric and gastroduodenal
intussusception was diagnosed and reduced surgically. A gastropexy was also
performed to prevent recurrence. On histopathology, the gastric glandular mucosa
showed moderate to marked proliferation. Diffusely lining the luminal surface of
glandular epithelium and free within the lumen were a myriad of protozoa
consistent with Cryptosporidium sp. A diagnosis of chronic proliferative
gastritis due to Cryptosporidium sp. was made based on these findings.
Intussusceptions are rare in reptiles and are infrequently reported in snakes.
This is the first report of a double compounded intussusception in a nonmammalian
species and the first report of an intussusception involving the stomach in a
snake with gastritis due to Cryptosporidium sp.
PMID- 29955429
TI - Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition.
AB - Glucose-6-phosphate dehydrogenase (G6PD) is an oncoprotein that is overexpressed
in cancer cells to provide the NADPH required for their increased anabolism.
NADPH, sourced from G6PD fuels nucleotide biosynthesis, maintains redox potential
of thioredoxin and glutathione and drives the mevalonate pathway that powers many
of the basic mechanisms by which cancer cells escape host control. G6PD is thus a
target for cancer treatment being addressed by many groups around the world. We
have discovered that systemic inhibition of G6PD by high dose
dehydroepiandrosterone (DHEA) causes a severe autoinflammatory response in dogs,
which does not occur in mice or rats. Since dogs more closely model the human
adrenal androgen system than do common laboratory animals, this finding is
relevant to the design of G6PD-inhibiting drugs for humans. The autoinflammatory
reaction observed closely resembles mevalonate kinase deficiency (MKD), a rare
autosomal recessive disease in humans characterized by recurrent febrile attacks,
arthralgia, skin rash, and aphthous ulcers of mucocutaneous tissues. In a manner
comparable to animal models of MKD, the reconstitution of protein
geranylgeranylation blocked the autoinflammatory reaction caused by systemic G6PD
inhibition. This autoinflammatory response to systemic G6PD inhibition represents
an unexpected result that must be taken into consideration when targeting this
oncoprotein.
PMID- 29955430
TI - Histological and Immunohistochemical Characterization of a Case of Endometriosis
in a Guinea Pig (Cavia tschudii).
AB - Endometriosis is a chronic gynecological disease characterized by the ectopic
proliferation of endometrial tissue outside of the uterine cavity. The
pathogenesis of this disease is still obscure, and Sampson's theory of retrograde
menstruation is still the most widely accepted explanation. Endometriosis in
animals has been so far described not only in baboons and a rhesus macaque but
also in dogs and horses that are nonmenstruating animals. In this article, we
report the histological and immunohistochemical characterization of the first
case of ovarian cystic endometriosis and adenomyosis in a guinea pig. The case
presented supports the hypothesis that endometriosis is a disease not at all
related to the phenomenon of retrograde menstruation but is a consequence of some
alterations in the morphogenesis of the female genital system and therefore it
could be found in any mammal. We suggest considering endometriosis among the
other pathological phenotypes in animals displaying ovarian and uterine
alterations and having a history of difficulties in conceiving.
PMID- 29955431
TI - Injection-Site Sarcoma in a Dog: Clinical and Pathological Findings.
AB - This case report documents the clinical and pathological findings in a dog that
rapidly developed a high-grade sarcoma at the site of multiple vaccinations and
follows the response to surgery and adjunct treatment with toceranib. An 11-year
old female spayed Labrador Retriever presented with dorsocervical subcutaneous
masses at the injection site three weeks after receiving DA2PP-Lepto, Rabies, and
Bordetella vaccinations. A high-grade soft tissue sarcoma was diagnosed
microscopically and immunohistochemistry revealed positive expression of VEGFr,
PDGFr, SCF, and EGFR. Repeat surgical resections and targeted treatment with
toceranib resulted in a stable remission for nearly two years.
PMID- 29955432
TI - Intertarsal Joint Stabilization in a Bateleur Eagle (Terathopius ecaudatus) Using
a Novel Application of a Braided Suture and Titanium Button System.
AB - A 32-year-old adult captive male bateleur eagle (Terathopius ecaudatus) with a
history of laxity, degenerative joint disease, and varus deviation of the distal
left hindlimb for several years was presented for evaluation of left hindlimb
lameness and was diagnosed with chronic subluxation of the left intertarsal
joint. After failing to improve with conservative management and pain medication,
surgical stabilization of the joint was performed using a novel application of a
braided suture and titanium button system. Unsatisfactory clinical improvement
and postsurgical reevaluation indicated that the initial surgical stabilization
was unsuccessful. The surgery was repeated, and the animal showed postsurgical
improvement in intertarsal joint stability, weight-bearing, and lameness for a
period of several years with use and adjustment of chronic pain medications. The
novel surgical technique described in this case report represents an additional
treatment option for management of avian intertarsal joint subluxations.
Presurgical planning should consider the unique anatomic features and variability
of the avian tarsometatarsus to avoid surgical complications.
PMID- 29955433
TI - Novel Treatment of Disseminated Coccidioidomycosis in a Dog with Voriconazole.
AB - A dog with disseminated coccidioidomycosis involving the vertebral, cutaneous,
and pulmonary systems was treated successfully with voriconazole after failing
traditional therapy with fluconazole and terbinafine. This report is the first to
describe the successful management of refractory coccidioidomycosis with
voriconazole in a dog.
PMID- 29955434
TI - Use of the Minimally Invasive Reduction Instrumentation System for Facilitating
Alignment and Reduction When Performing Minimally Invasive Plate Osteosynthesis
in Three Dogs.
AB - The Minimally Invasive Reduction Instrumentation System (MIRIS) was utilized to
facilitate minimally invasive plate osteosynthesis (MIPO) of distal limb
diaphyseal comminuted fractures (2 crural, 1 antebrachial) in three dogs. The
MIRIS facilitated efficient MIPO in all three fractures. Radial and tibial
lengths were restored within 2% of the length of the intact bone and
postoperative frontal and sagittal plane angulation were within 3 degrees of the
normal contralateral limb for each of the fractures. Fixation failed in one of
the tibial fractures when the plates bent a week following surgery. The implants
were removed and the fracture was restabilized via MIPO facilitated by the MIRIS.
Inappropriate implant selection was considered the primary reason for implant
failure. All three fractures achieved union by 10 weeks following surgery. The
dog that underwent revision surgery developed a surgical site infection 5 months
following revision surgery, which necessitated implant removal. All three dogs
had excellent limb function at the time of the final evaluation. This system
resulted in reductions that were near anatomic, with acceptable restoration of
length and alignment and excellent limb function.
PMID- 29955435
TI - Aspergillus Section Nigri-Associated Calcium Oxalate Crystals in an Eurasian
Eagle Owl (Bubo bubo).
AB - An adult male Eurasian eagle owl (Bubo bubo) housed at a wildlife rehabilitation
facility in southern Oregon died after a short period of progressive ill-thrift.
Radiographs taken prior to death demonstrated abnormal radiopaque material in the
coelom and the owl was submitted for postmortem examination. Black pigmented
fungus was noted grossly, particularly in the respiratory tissues, with abundant
oxalate crystal deposition associated with and without hyphal elements
subsequently observed histologically. Aspergillus section Nigri was cultured from
the lesions. Although there have been a few reports of aspergillosis caused by
Aspergillus niger in avian species, the severity and wide tissue distribution of
oxalates in this case are highly unusual.
PMID- 29955436
TI - Enucleation in a Cownose Ray (Rhinoptera bonasus).
AB - Trauma is a common problem in Cownose Ray during mating season in both wild and
captive rays. Enucleation is indicated when there is an ocular trauma. A 5-year
old female Cownose Ray (Rhinoptera bonasus) from Aquaria of Kuala Lumpur
Convention Centre (KLCC) was presented to University Veterinary Hospital (UVH),
Universiti Putra Malaysia, with a complaint of protruding left eye, which
resulted from crushing into artificial coral during mating season. There were a
hyphema in the traumatic left eye, periorbital tissue tear, exposed left eye
socket, and multiple abrasions on both pectoral fins. The Cownose was
anaesthetized and maintained with isoeugenol and on-field emergency enucleation
of the left eye was performed. It was managed medically with postoperative
enrofloxacin, tobramycin ointment, and povidone iodine. No suture breakdown and
secondary infection were observed at day 7 after enucleation during revisit. At
day 24 after enucleation, the Cownose responded well to treatment with excellent
healing progression and no surgical complication was observed.
PMID- 29955437
TI - Hemangiosarcoma in a Dog: Unusual Presentation and Increased Survival Using a
Complementary/Holistic Approach Combined with Metronomic Chemotherapy.
AB - This case report documents the clinical and pathologic findings in a 12-year-old
terrier mix with intraocular and splenic hemangiosarcoma. Pathologic findings in
both the spleen and globe were consistent with hemangiosarcoma with a low mitotic
count. Initial treatment consisted of enucleation and then splenectomy followed
by one cycle of conventional doxorubicin chemotherapy. Due to poor tolerance, a
subsequent treatment regimen consisted of metronomic chemotherapy with
chlorambucil combined with an alternative/complementary regimen of I'm-Yunity
(polysaccharopeptide) and Yunnan Baiyao. Follow-up thoracic radiographs and
abdominal ultrasounds over a period of 24 months showed no evidence of pulmonary,
hepatic, or right atrial metastases, during which time the patient had an
excellent quality of life. However, shortly after achieving two-year survival,
the patient developed new onset seizures unresponsive to anticonvulsant therapy.
Therefore, a decision was made to euthanize the dog given that the most likely
etiology of the seizures was a brain tumor. Overall, this is an exceptional
treatment response given the poor survival statistics of hemangiosarcoma even
with conventional chemotherapy. However, additional clinical pharmacology and
clinical trial data are needed to further support the use of a
complementary/holistic approach in combination with metronomic chemotherapy.
PMID- 29955438
TI - Cocoa Pod Husk Pectin Intended as a Pharmaceutical Excipient Has No Adverse
Effects on Haematological Parameters in Sprague Dawley Rats.
AB - Natural polymer research has recently become the focus of intensive research in
the quest for new enabling excipients for novel drugs in pharmaceutical
formulation for optimal treatment outcomes. Evaluations of some excipients have
shown deleterious haematological effects of varying extents on the safety profile
of these excipients. A 90-day subchronic toxicity study was conducted to evaluate
the influence of cocoa pod husk (CPH) pectin on indicators for haematotoxicity.
Male and female Sprague Dawley rats (SDRs) were fed with CPH pectin in doses up
to 71.4 mg/kg. The effects of CPH pectin on the haematological indices, direct
and total bilirubin, and the spleen were determined. The results indicated that
CPH pectin did not induce any untoward toxic effects on the haematological
indices, bilirubin levels, and the spleen. There were, however, elevations in MCV
at day 30, which was not sustained after the 90 days. The data obtained from this
study did not reveal any remarkable findings of toxicological relevance to the
haematopoietic system.
PMID- 29955439
TI - Antibiotic-loaded nanoparticles targeted to the site of infection enhance
antibacterial efficacy.
AB - Bacterial resistance to antibiotics has made it necessary to resort to
antibiotics that have considerable toxicities. Here, we show that the cyclic 9
amino acid peptide CARGGLKSC (CARG), identified via phage display on
Staphylococcus aureus (S. aureus) bacteria and through in vivo screening in mice
with S. aureus-induced lung infections, increases the antibacterial activity of
CARG-conjugated vancomycin-loaded nanoparticles in S. aureus-infected tissues and
reduces the needed overall systemic dose, minimizing side effects. CARG binds
specifically to S. aureus bacteria but not Pseudomonas bacteria in vitro,
selectively accumulates in S. aureus-infected lungs and skin of mice but not in
non-infected tissue and Pseudomonas-infected tissue, and significantly enhances
the accumulation of intravenously injected vancomycin-loaded porous silicon
nanoparticles bearing the peptide in S. aureus-infected mouse lung tissue. The
targeted nanoparticles more effectively suppress staphylococcal infections in
vivo relative to equivalent doses of untargeted vancomycin nanoparticles or of
free vancomycin. The therapeutic delivery of antibiotic-carrying nanoparticles
bearing peptides targeting infected tissue may help combat difficult-to-treat
infections.
PMID- 29955440
TI - The Relationship between Food Insecurity, Dietary Patterns, and Obesity.
AB - Food insecurity is a major public health concern, and refers to the uncertainty,
lack of, or inability to acquire nutritious food in a safe and socially
acceptable manner. Food insecurity has been associated with obesity and unhealthy
dietary patterns, both of which can have negative health consequences. A review
of the current literature revealed an adverse association between food insecurity
and dietary patterns is well supported. The association between food insecurity
and obesity is strongest for women, with results for men and children being
mixed. Evidence for long-term effects is limited due to a lack of longitudinal
studies. Results from interventional studies have mostly yielded mixed results,
and it is presently unclear how to best help food insecure individuals improve
diet and weight.
PMID- 29955441
TI - Utilization of antipsychotic therapeutic drug monitoring at a state psychiatric
hospital.
AB - Introduction: This study assesses the utilization of antipsychotic therapeutic
drug monitoring (TDM) and describes characteristics of appropriate and
inappropriate TDM at a state psychiatric hospital. Methods: A retrospective,
descriptive review was conducted for antipsychotic TDM completed between December
1, 2009, and June 30, 2011, at a 65-bed adult inpatient extended-care and
forensic state psychiatric hospital. Results: One hundred thirty-three (n = 133)
antipsychotic serum levels were collected from 44 patients during the study
period. Sixty-nine percent (69%) of the TDM were deemed inappropriate, 28% were
appropriate, and 3% could not be designated appropriate or inappropriate owing to
the lack of information regarding steady-state conditions. The primary reason for
inappropriate TDM was lack of documentation with regard to the indication for TDM
(n = 79, 59.3%), the intervention following laboratory analysis (n = 88, 66%), or
both. Appropriate TDM was associated with a lower laboratory cost for
antipsychotic serum level ($48.98 +/- $53.49 versus $72.06 +/- $51.02, P < .05),
lower daily cost of scheduled psychiatric medications ($17.72 +/- $23.03 versus
$32.26 +/- $31.05, P < .05), lower daily cost of total medications ($19.28 +/-
$24.91 versus $33.82 +/- $31.03, P < .05), fewer scheduled psychiatric
medications (2.95 +/- 1.90 versus 4.04 +/- 2.19, P < .01), and fewer total
scheduled medications (5.95 +/- 3.60 versus 7.60 +/- 3.29, P < .05).
Inappropriate TDM led to approximately $6,753 in avoidable laboratory costs over
a 20-month period. Discussion: Therapeutic drug monitoring is a complex process
with many points at which errors may occur. The majority of antipsychotic levels
at this state psychiatric hospital were not documented in a way that was
clinically useful. Inappropriate TDM was associated with increased laboratory and
medication costs.
PMID- 29955442
TI - Pharmacokinetic characteristics of antiepileptic drugs (AEDs).
AB - Antiepileptic drugs (AEDs) are routinely prescribed for the management of a
variety of neurologic and psychiatric conditions, including epilepsy and epilepsy
syndromes. Physiologic changes due to aging, pregnancy, nutritional status, drug
interactions, and diseases (ie, those involving liver and kidney function) can
affect pharmacokinetics of AEDs. This review discusses foundational
pharmacokinetic characteristics of AEDs currently available in the United States,
including clobazam but excluding the other benzodiazepines. Commonalities of
pharmacokinetic properties of AEDs are discussed in detail. Important differences
among AEDs and clinically relevant pharmacokinetic interactions in absorption,
distribution, metabolism, and/or elimination associated with AEDs are
highlighted. In general, newer AEDs have more predictable kinetics and lower
risks for drug interactions. This is because many are minimally or not bound to
serum proteins, are primarily renally cleared or metabolized by non-cytochrome
P450 isoenzymes, and/or have lower potential to induce/inhibit various hepatic
enzyme systems. A clear understanding of the pharmacokinetic properties of
individual AEDs is essential in creating a safe and effective treatment plan for
a patient.
PMID- 29955443
TI - A review of pharmacokinetic and pharmacodynamic interactions with antipsychotics.
AB - Introduction: Antipsychotics are widely used and often in combination with other
drugs, thereby frequently subjected to drug-drug interactions. This review will
provide a summary of potential pharmacokinetic (PK) and pharmacodynamic (PD) drug
interactions associated with antipsychotic drugs. Methods: A literature search
was conducted for clinically significant drug interactions with antipsychotics.
Results: Most common PK drug interactions take place via the cytochrome P450
(CYP) system. PK profiles of first generation antipsychotics are inadequately
studied; nevertheless most common drug interactions involve changes to their
metabolic processes. Interactions with second generation antipsychotics are
somewhat well-established, documented, and give some guidance for therapeutic
treatment interventions. PD interactions occurring at the receptor level result
in additive, synergistic, or antagonistic effects. Discussion: This review
summarizes a collection of relevant literature of significant PK and PD
interactions occurring with antipsychotics. The involvement of multiple CYP
enzymes makes it more difficult to predict the extent of the interaction and
clinicians should take into consideration the timeline when evaluating potential
interactions.
PMID- 29955444
TI - Pharmacogenetics of antiepileptic drugs: A brief review.
AB - The goal of pharmacogenetic research is to assist clinicians in predicting
patient response to medications when genetic variations are identified. The
pharmacogenetic variation of antiepileptic drug response and side effects has
yielded findings that have been included in drug labeling and guidelines. The
goal of this review is to provide a brief overview of the pharmacogenetic
research on antiepileptic drugs. It will focus on findings that have been
included in drug labeling, guidelines, and candidate pharmacogenetic variation.
Overall, several genes have been included in guidelines by national and
international organizations; however, much work is needed to implement and
evaluate their use in clinical settings.
PMID- 29955445
TI - A review of significant pharmacokinetic drug interactions with antidepressants
and their management.
AB - Treatment of depression often requires long-term management with medication.
Practitioners should be aware of potentially significant drug interactions with
the use of antidepressants in order to effectively prevent or manage adverse
events while optimizing patient response to treatment. Most antidepressants are
metabolized by the liver, primarily via the CYP450 system. Pharmacokinetic
profiles of the most recently approved antidepressants are reviewed in addition
to evidence supporting potentially significant interactions. In addition,
pharmacokinetic interactions between multiple antidepressants and other drug
classes, including opiates, antineoplastics, antiepileptics, and antipsychotics,
are discussed. This article provides recommendations for the monitoring and
management of drug interactions. In addition, limitations of the evidence are
reviewed.
PMID- 29955446
TI - Urine drug screens: Considerations for the psychiatric pharmacist.
AB - Introduction: Proper psychiatric evaluation of patients necessitates that the
clinician be vigilant in ruling out secondary causes of symptoms, such as
substance-induced symptoms. Immunoassay-type urine drug screens (UDSs) offer
clinicians rapid drug screen results, ease of use, and inexpensive cost.
Unfortunately, these screens are not without their limitations. This review aims
to outline the nuances and limitations of immunoassay UDSs and to provide the
clinician with information that facilitates more accurate interpretation of UDS
results. Specifically, false positive results associated with psychiatric
medications and the availability and methods for acquisition of commercialized
UDS masking agents will be reviewed. Methods: A literature review was conducted
to identify false positive UDSs associated with psychiatric medications.
References for each article identified were also reviewed. Additionally, a
Google(r) search was conducted to identify commercially available preparations
used to mask UDS results and the methods of acquisition of these products.
Results: A total of 14 articles were identified using PubMed. No articles for
mood stabilizing agents were identified. Entering the phrase how to pass a drug
test into Google(r) search yielded about 12.6 million results, and select
references were reviewed based on relevance and user reviews. Discussion: Several
psychiatric medications are documented as potential sources of false positive
UDSs. Additionally, several agents are available for consumer purchase that may
result in false negative UDSs. The clinician must be vigilant in interpreting
immunoassay UDS results and should utilize more advanced forms of testing as
clinically appropriate.
PMID- 29955447
TI - Pharmacogenomics: A focus on antidepressants and atypical antipsychotics.
AB - The study of pharmacogenomics is rapidly growing, particularly in the field of
mental health. Understanding pharmacogenomic principles can be a challenge for
many clinicians. Most mental health genomic data concentrates on variability
(response, side effects) with antidepressants and atypical antipsychotics.
Current pharmacogenomic practice and research primarily focuses on two areas:
pharmacodynamics and pharmacokinetics. Based on the current literature, genetic
polymorphisms of pharmacodynamics and pharmacokinetics parameters likely
influence medication efficacy, therefore affecting the therapeutic benefit.
Additionally, certain pharmacodynamic and pharmacokinetic polymorphisms have been
linked to an elevated risk of side effects and adverse events with these
medications. In this review, specific pharmacodynamic and pharmacokinetic
polymorphisms related to antidepressants and atypical antipsychotics will be
discussed, as well as the potential clinical effect these genomic abnormalities
have within psychiatric care.
PMID- 29955448
TI - General pharmacokinetic/pharmacodynamic concepts of mood stabilizers in the
treatment of bipolar disorder.
AB - Introduction: Mood stabilizers are the recommended treatment for patients who
receive a diagnosis of bipolar disorder. Because of the necessity of mood
stabilizer treatment in patients with bipolar disorder and the extent of
pharmacokinetic and pharmacodynamic principles involved, the purpose of this
review is to summarize the pharmacokinetic principles of lithium in addition to
the pharmacodynamics of lithium, carbamazepine, lamotrigine, and valproic
acid/valproate. Methods: Practice guidelines, review articles, and clinical
trials were located using online databases PubMed, CINAHL, IDIS, and Medline.
Search terms included at least one of the following: bipolar disorder,
carbamazepine, lamotrigine, lithium, mood stabilizers, pharmacokinetics,
pharmacodynamics, valproate, and valproic acid. Online clinical databases
Dynamed(r) and Lexicomp(r) were also used in the study. Results: Mood stabilizers
collectively possess distinct qualities that are closely regarded before, during,
and after therapeutic initiation. Individual patient characteristics, coupled
with these observed traits, add to the complexity of selecting the most optimal
neurologic agent. Each medication discussed uniquely contributes to both the
maintenance and restoration of overall patient well-being. Discussion:
Introduction of mood stabilizers into drug regimens is often done in the presence
of an array of mitigating factors. Safety and efficacy measures are commonly used
to gauge desired results. Careful monitoring of patients' responses to selected
therapies is paramount for arriving at appropriate clinical outcomes.
PMID- 29955449
TI - Dialectical behavior therapy as treatment for borderline personality disorder.
AB - Dialectical behavior therapy (DBT) is a structured outpatient treatment developed
by Dr Marsha Linehan for the treatment of borderline personality disorder (BPD).
Dialectical behavior therapy is based on cognitive-behavioral principles and is
currently the only empirically supported treatment for BPD. Randomized controlled
trials have shown the efficacy of DBT not only in BPD but also in other
psychiatric disorders, such as substance use disorders, mood disorders,
posttraumatic stress disorder, and eating disorders. Traditional DBT is
structured into 4 components, including skills training group, individual
psychotherapy, telephone consultation, and therapist consultation team. These
components work together to teach behavioral skills that target common symptoms
of BPD, including an unstable sense of self, chaotic relationships, fear of
abandonment, emotional lability, and impulsivity such as self-injurious
behaviors. The skills include mindfulness, interpersonal effectiveness, emotion
regulation, and distress tolerance. Given the often comorbid psychiatric symptoms
with BPD in patients participating in DBT, psychopharmacologic interventions are
oftentimes considered appropriate adjunctive care. This article aims to outline
the basic principles of DBT as well as comment on the role of pharmacotherapy as
adjunctive treatment for the symptoms of BPD.
PMID- 29955450
TI - Psychotropic medication use in hospitalized patients with borderline personality
disorder.
AB - Introduction: Use of medications to treat symptoms of borderline personality
disorder (BPD) is controversial. The purpose of this study was to describe
psychotropic medication use in hospitalized patients with BPD and compare with a
control group. Methods: A retrospective chart review was conducted on
hospitalized patients aged 18-65 years having a diagnosis of BPD and compared
them with a control group of patients with a diagnosis of major depressive
disorder (MDD) without a personality disorder. Patients were excluded from the
BPD group if other personality disorders were recorded. Charts were reviewed for
demographics and psychotropic medication usage both prior to admission and at
discharge. Results: This study included 165 patients (85 in BPD; 80 in MDD).
Prior to admission and upon discharge, patients in the BPD group were prescribed
significantly more psychotropic medications than patients with MDD (3.21 vs 2.10;
P < .001 and 2.87 vs 2.35; P < .05, respectively). Patients in the BPD group were
significantly more likely to be prescribed antipsychotics, mood stabilizers, and
miscellaneous agents compared with the MDD group. On admission, significantly
more BPD patients were prescribed multiple sedative agents (37.6% vs 21.3%; P <
.05), but because of the discontinuation of sedative agents, this difference was
nonsignificant upon discharge. Discussion: This study found increased medication
utilization among patients with BPD. Polypharmacy may increase the risk of side
effects, drug interactions, and drug toxicity for BPD patients. Clinicians need
to carefully evaluate the efficacy and risk of medications prescribed in patients
with BPD.
PMID- 29955451
TI - Review of pharmacologic treatment in cluster A personality disorders.
AB - Introduction: A personality disorder is a pervasive and enduring pattern of
behaviors that impacts an individual's social, occupational, and overall
functioning. Specifically, the cluster A personality disorders include paranoid
personality disorder, schizoid personality disorder, and schizotypal personality
disorder. Patients with cluster A personality disorders tend to be isolative and
avoid relationships. The quality of life may also be reduced in these
individuals, which provokes the question of how to treat patients with these
personality disorders. The purpose of this review is to evaluate the current
literature for pharmacologic treatments for the cluster A personality disorders.
Methods: A Medline/PubMed and Ovid search was conducted to identify literature on
the psychopharmacology of paranoid personality disorder, schizoid personality
disorder, and schizotypal personality disorder. There were no exclusions in terms
of time frame from article publication or country of publication, in order to
provide a comprehensive analysis; however, only articles that contained
information on the cluster A disorders were included. Results: Minimal evidence
regarding pharmacotherapy in paranoid and schizoid personality disorders was
found. Literature was available for pharmacologic treatment of schizotypal
personality disorder. Studies evaluating the use of olanzapine, risperidone,
haloperidol, fluoxetine, and thiothixene did yield beneficial results; however,
treatment with such agents should be considered on a case-by-case basis.
Discussion: Most of the literature analyzed in this review presented theoretical
ideas of what may constitute the neurobiologic factors of personality and what
treatments may address these aspects. Further research is needed to evaluate
specific pharmacologic treatment in the cluster A personality disorders. At this
time, treatment with pharmacologic agents is based on theory rather than
evidence.
PMID- 29955452
TI - Second-generation antipsychotic use in borderline personality disorder: What are
we targeting?
AB - Introduction: Borderline personality disorder (BPD) is a personality disorder
plagued with high rates of psychotropic polypharmacy. Estimates show that second
generation antipsychotics (SGAs) are used in most of these patients; however,
they are being prescribed off label. Methods: A literature review was conducted
via PubMed in search for studies evaluating SGA use in BPD. Results: There are
available data investigating 8 of 11 SGAs and their use in BPD. Of N = 269
potential articles, N = 34 evaluating the use of SGAs in BPD were included.
Discussion: Strong evidence supporting SGAs in BPD is lacking. Potential target
symptoms in which a SGA may be useful include depression, anxiety, anger,
impulsivity, and paranoia/dissociative behavior.
PMID- 29955453
TI - Identification, assessment, and management of pain in patients with advanced
dementia.
AB - Patients with advanced dementia have a high symptom burden at end of life. Many
of those with dementia have reports of symptoms similar to those without
dementia, yet are treated less frequently. Pain is a prevalent symptom that can
be underrecognized because of the ability of the patient to self-report. Several
tools are available to help with the identification of pain, but they should only
be one aspect in the overall assessment. Health care providers must anticipate
this and screen for and treat potential pain. This includes obtaining a self
report, searching for potential causes for pain, observing patient behavior,
gaining proxy reporting of pain, and attempting an appropriate analgesic trial.
It is beneficial for all those involved with a patient's care to screen for pain
because of the potential benefits in decreasing behaviors and subsequent
antipsychotic use.
PMID- 29955454
TI - A consumer-led intervention to improve pharmacists' attitudes toward mental
illness.
AB - Introduction: Individuals with a severe and persistent mental illness often
manage complex medication regimens and would benefit from support and education
from their pharmacist. Past research has shown that community pharmacists have
negative attitudes toward mental illnesses, and these attitudes affect
willingness to provide services to patients with mental illnesses. Consumer-led
interventions have shown benefit to improve student attitudes toward mental
illness. However, there are no known studies showing the benefit of consumer-led
educational programs to improve pharmacist attitudes toward mental illness and
willingness to provide services to those with mental illnesses. The aim of this
study is to determine the effects of a consumer-led continuing education program
on pharmacists' attitudes toward and willingness to provide services to consumers
with mental illnesses. Methods: Fifty pharmacists participated in the program
with 2 parts: discussion on the history of mental health care and consumers
sharing their experiences. Pharmacists completed 1 survey before and after the
program. Surveys asked about pharmacists' attitudes toward mental illness and
willingness to provide services to individuals with schizophrenia compared to
asthma. Data were analyzed using descriptive and paired t tests. Results: Paired
t tests showed a significant decrease in social distance and increase in positive
attitudes and willingness to provide services to patients with mental illnesses
immediately after the program. Discussion: The immediate increase in positive
attitudes and willingness to provide services to consumers with mental illnesses
indicates that consumer-led interventions may be an effective way to improve the
provision of pharmacy services to patients with mental illnesses.
PMID- 29955455
TI - A design and focus group evaluation of dietary choices tools for an underserved
population.
AB - Introduction: Our objective was to develop and evaluate dietary teaching tools
for a select population diagnosed with a severe mental illness and limited
financial ability. Patients with severe mental illnesses face many challenges,
including common health comorbidities of diabetes, high blood pressure, high
cholesterol, and obesity. Cognitive deficits may limit educational programming;
financial resources can affect access to a healthy diet. The Integrated
Multidisciplinary Program of Assertive Community Treatment (IMPACT) program, a
university-based program, provides individualized services to this population.
One focus is healthy nutritional choices. Methods: In Phase One, a clinical
pharmacist and a first-year pharmacy resident created visual aids. These cards
were given to health care providers (HCPs) to be used with IMPACT members. HCPs
were asked to participate in a focus group and provide feedback. Phase Two: Based
on specific focus group feedback, additional resources were created to address
identified nutritional needs. Results: Phase One: Ten cards were created and
distributed to the HCPs. A focus group was conducted. HCPs reported the cards
were useful in opening dietary choices dialogues and were able to give more
specific information on alternative choices. Phase Two: From focus group
feedback, specific cards for disease states, calorie guidelines, and budget
limitations were developed. HCPs immediately utilized them. Discussion: This
pilot project was used to design and create educational cards to facilitate
discussions on healthy or healthier dietary choices. Feedback from the HCPs
participating in the focus group was positive, and they were enthusiastic about
both sets of cards, particularly those pertaining to budget choices.
PMID- 29955456
TI - Suicide prevention in pharmaceutical education: Raising awareness with inspiring
stories.
AB - Suicide rates are high in high-income countries like Canada and the United
States, where 10 to 12 people per 100 000 commit suicide every year. In the
United States, in 2011 there were 73.3 emergency room visits per 100 000 people
for suicide attempts with prescription drugs. The latter were also involved in
13% of completed suicides between 1999 and 2013. In most cases, these drugs were
distributed by members of our profession who could not predict this outcome. This
led us to create an initiative to teach pharmacy students how to prevent suicide.
A literature review and online search were performed to find documentation about
pharmacists' commitment to the cause, but very little information exists. Thus, a
training session was developed for third-year pharmacy students that includes
basic statistics, arguments for involving pharmacists in suicide prevention, role
playing, tools to evaluate suicide risk, thoughtful verbatims of interview
techniques, and case studies. It is delivered during the mental health theme of
the psychiatry course. In 5 years, around 1150 students have participated in the
course, of whom approximately 950 are now practicing pharmacists. This
intervention may have prevented some suicides, although the impact is impossible
to measure. The objective of this paper is to describe the creative process of
designing a suicide prevention training session for pharmacy students, while
inspiring a mental health sensitive readership to this noble cause. This article
does not provide guidelines on how to replicate this initiative, nor does this
article replace proper training on suicide prevention.
PMID- 29955457
TI - Evaluating nursing satisfaction and utilization of the Clinical Institute
Withdrawal Assessment for Alcohol, revised version (CIWA-Ar).
AB - Introduction: The Clinical Institute Withdrawal Assessment for Alcohol, revised
version (CIWA-Ar), developed and validated for research, is used in our inpatient
academic medical center. We sought to assess nursing satisfaction with the scale
itself, training for using the scale, and nursing staff use of the CIWA-Ar.
Methods: A retrospective chart review included all patients with an order for
CIWA-Ar between August 1, 2014, and September 30, 2014. Data collected included
demographics, admitting diagnosis, vital signs, admission blood alcohol level,
lorazepam total daily dose, and CIWA-Ar scores. Nursing staff was sent an
anonymous, 26-question survey in January 2015. The survey collected demographics,
training history, and recommendations for modifications to the CIWA-Ar. Results:
During the 2-month period, 274 patients had orders for CIWA-Ar, with 113
receiving at least one dose of lorazepam. Lorazepam was not given to 21% of
patients when they scored >8 on the CIWA-Ar, whereas 71% of patients received a
dose of lorazepam when they had a CIWA score <8. The survey was sent to 2011
clinical nurses, with 284 responses received (14% response rate). Only 36% of
responding nurses felt adequately trained to administer the CIWA-Ar. Most nurses
preferred on-the-job and online training methods. Discussion: Nursing use of the
CIWA-Ar could be optimized at this institution. Fewer than half of respondents
reported feeling adequately training to administer the CIWA-Ar. Results will be
used to improve training for nursing staff regarding scoring of the CIWA-Ar and
administering lorazepam to treat alcohol withdrawal syndrome.
PMID- 29955458
TI - Benzodiazepine use, misuse, and abuse: A review.
AB - Benzodiazepine (BZD) abuse has reached epidemic levels and results in poor
outcomes, particularly when combined with concomitant central nervous system
depressants. BZDs are abused most commonly in combination with opioids and
alcohol. Emergency department visits and related deaths have soared in recent
years. In the absence of other medications or illicit substances, BZDs are rarely
the sole cause of death. Prescription drug abuse has received more attention in
recent years, yet much remains unknown about BZD abuse. BZDs have low abuse
potential in most of the general population. A subset is at elevated risk of
abuse, especially those with a history of a substance use disorder. Education,
prevention, and identification are vital in reducing BZD abuse.
PMID- 29955459
TI - Buprenorphine/naloxone addiction in a pharmacist as a result of migraine self
treatment.
AB - Objective: A unique case report is presented to demonstrate addiction in a
pharmacist through the use of buprenorphine/naloxone film for the self-prescribed
treatment of migraine headaches. Case Summary: A 35-year-old female hospital
pharmacist was admitted to treatment for opioid use disorder for using
buprenorphine/naloxone film to self-medicate her migraine headaches. After daily
use of sublingual buprenorphine/naloxone, and several failed attempts to
discontinue use, the pharmacist was admitted to a partial hospitalization
treatment program. She was prescribed sumatriptan subcutaneous injection for her
migraines, while maintaining buprenorphine/naloxone abstinence. Upon completion,
the pharmacist transitioned to the aftercare program, where she maintains
sobriety and uses her story to help aid in other patients' recoveries at the
treatment center. Discussion: Addiction and substance abuse affect a substantial
number of health care professionals. Pharmacists are particularly vulnerable to
prescription drug misuse and addiction as a result of their direct access and
vast pharmacologic knowledge. In a 2004 self-report survey of a random sample of
health care providers, 58.7% of pharmacists reported using nonprescribed
prescription drugs at least once in their lifetime. This case is a story of
rehabilitation and recovery of a pharmacist who has a desire to return to the
practice of pharmacy through the use of effective pharmacologic and behavioral
interventions.
PMID- 29955460
TI - Intolerance of sublingual buprenorphine-naloxone during induction in a patient
with end-stage liver disease: A case report.
AB - Introduction: Sublingual buprenorphine is indicated for opioid dependence. It
comes in 2 formulations: a mono buprenorphine product (BUP) and a combination
product containing naloxone (BUP-NAL), which functions as an abuse deterrent.
Sublingual naloxone does not reach clinically significant levels except in cases
of hepatic impairment, where its metabolism can be impaired. Substantial naloxone
accumulation could block the therapeutic effects of buprenorphine. The risk of
hepatic impairment is elevated in the opioid dependence population, and our case
highlights the need for careful evaluation of hepatic function and consideration
of BUP. Case/Results: We report a patient with end-stage liver disease who began
BUP-NAL induction with modest improvement on treatment day 1 followed by
sustained withdrawal after receiving an observed dose on day 2. He returned to
the clinic 2 days after his second successive day of BUP-NAL, vomiting and
complaining of persistent withdrawal. To avoid potential accumulation of
naloxone, the patient was eventually switched to and stabilized on BUP with good
response. Discussion/Conclusion: The clinical course this patient experienced
during induction makes a case that naloxone can accumulate and interfere with the
effectiveness of buprenorphine in the presence of liver dysfunction. Our case
highlights the need for consideration of BUP in circumstances where patient
safety and effective treatment outweigh the risks of prescribing a product with
abuse deterrent properties.
PMID- 29955461
TI - Hospitalizations and emergency room visits after initiation of long-acting
injectable antipsychotics.
AB - Introduction: Long-acting injectable antipsychotics (LAIs) serve as a means to
ensure medication adherence with the intention of improving outcomes for
psychiatric patients. Evidence remains inconclusive regarding the impact of LAIs
on relapses and psychiatric hospitalizations rates. Methods: The primary
objective of this retrospective pre/post study was to determine whether
initiating an LAI in a veteran population with schizophrenia, schizoaffective
disorder, or bipolar disorder is associated with a decrease in the 1-year rate of
psychiatric hospitalizations and emergency room (ER) visits. Results: For the
combined primary endpoint, the 1-year rate of psychiatric hospitalizations and ER
visits for patients with schizophrenia, schizoaffective disorder, or bipolar
disorder was not significantly reduced after initiation of LAIs (n = 50, median
[interquartile range]: 1.5 [1, 3] to 1 [0, 3], P = .055). However, the secondary
endpoint of the 1-year rate of psychiatric hospitalizations was reduced (1 [0, 3]
to 0 [0, 2], P = .026). Additionally, for those who received injections on a
regular basis, the 1-year rate of hospitalizations and ER visits was
significantly reduced (2 [1, 3] to 0 [0, 1.5], P = .009). Discussion: This
retrospective study suggests that the initiation of LAIs is associated with a
reduced rate of psychiatric hospitalizations as well as a reduced rate of
psychiatric hospitalizations and ER visits for those patients who receive
injections on a regular basis.
PMID- 29955462
TI - Using Photovoice to explore patients' experiences with mental health medication:
A pilot study.
AB - Introduction: The objective of this research is to explore and share the
medication experience of those with a mental illness in order to gain
understanding of the patient's medication perceptions as well as the impact of
medication upon patients' lives. Methods: Patients with a mental disorder were
given cameras and asked to capture the experience of "living with my medication."
Using Photovoice methodology, participants reflected on their photos individually
and in focus groups. Conceptual themes were drawn from the data. Results: Five
participants captured an average of 14 photos each. Self-efficacy with mental
illness, mental and physical health connections, and education were the 3 most
prominent themes. Aspects of medications were interwoven within these themes but
were not the primary focus of the participants. Discussion: Medication
experiences of patients with mental illness may encompass much more than the
medications themselves.
PMID- 29955463
TI - Management of migraine headaches in a chronic pain patient: A case report.
AB - Managing migraines complicated with medication overuse headaches and opioid
induced hyperalgesia can be challenging, especially within the geriatric and
chronic pain population. A 65-year-old woman with a degenerative spine condition
and chronic migraine headaches, along with other comorbidities, was admitted to
the geriatric psychiatry unit for extreme mood swings and paranoia. Prior to
admission, she had been taking extended-release morphine sulfate twice daily for
more than a month and was unable to determine triggers to her frequent migraine
headaches. She had a history of medication overuse and severe migraine episodes
within 4 weeks prior to admission. This case report reviews the challenges of
treating a geriatric patient with probable chronic migraines in addition to other
pain conditions and comorbidities.
PMID- 29955464
TI - Implementation and evaluation of a pharmacist-run mental health treatment clinic
via clinical video telehealth.
AB - Introduction: The Veterans Health Administration is extending its mental health
services to reach those in rural areas who find it difficult to travel to a
Veterans Affairs Medical Center (VAMC). This project aimed to outline
implementation of a Pharmacy Mental Health Clinical Video Telehealth (MHCVT)
clinic for veterans. Secondary endpoints were to assess patient satisfaction with
MHCVT, describe the potential benefits of this clinic regarding travel saved, and
summarize no-show rates. Methods: Veterans received mental health disease state
medication management from a mental health clinical pharmacy specialist via
clinical video telehealth (CVT) in place of an in-clinic appointment and were
asked to complete a satisfaction survey after the initial CVT appointment. Data
collected from all veterans enrolled in the CVT clinic from September 8, 2014,
through March 23, 2015 included: patient demographics, service connection
percentage, number of CVT visits, travel miles saved, travel reimbursement, no
show rate, and documentation of medication management therapy. Results: As of
March 23, 2015, there were 22 veterans enrolled in the MHCVT clinic, of whom, 19
completed their appointments. Of the 48 potential encounters, 7 were considered a
no-show (17%). On average veterans saved 34 travel miles per visit with
cumulative savings of 1432.6 miles. Of those who were eligible to receive travel
reimbursement (n = 13), the medical center potentially saved $674.50 in a 7-month
period. Overall clinic satisfaction per survey (n = 14) was 100% (strongly agreed
or agreed). A majority (93%) would recommend the clinic to other veterans.
Conclusions: This project successfully implemented a MHCVT pilot clinic. The
veterans were satisfied with the services. The 41 clinic visits resulted in a
potential cost savings. Expansion of this clinic in the future will expand more
mental health resources to veterans.
PMID- 29955466
TI - Evaluation of the use of electrocardiogram monitoring in patients on psychotropic
medications that have a risk of QT prolongation.
AB - Introduction: Many psychotropic medications carry a risk of prolonging the QT
interval and increasing the risk of developing Torsade de pointes (TdP). The goal
of this study was to evaluate whether patients taking psychotropic agents with a
known risk of TdP are being monitored at a community hospital through the use of
electrocardiograms (EKGs). Methods: This was a retrospective chart review of 100
adult patients-50 from general medicine floors and 50 from psychiatric units-who
were taking at least one psychotropic agent with a known risk of TdP during
hospitalization. Results: The mean number of medications with QT-prolongation
risk administered to the psychiatric and general medicine patients was 4.2 +/-
1.7 and 3.9 +/- 2.0, respectively (P = .7484). Thirty-two of the psychiatric
patients (64%) and 48 of the general medicine patients (96%) received EKGs during
their hospitalization (P < 0.0001). Of those newly starting the target
medications, 58% (18 of 31) of the psychiatric patients and 71% (5 of 7) of the
general medicine patients received a baseline EKG. The difference was not
statistically significant (P = .6807). Overall, 8 patients (8%) had corrected QT
(QTc) intervals >500 ms. Four had repeat EKGs performed, and none had medication
changes made to decrease TdP risk. Discussion: Many inpatients on psychiatric
medications received multiple medications with a risk of TdP, but not all
received monitoring through baseline or repeat EKGs when warranted. Patients with
QTc intervals >500 ms were not appropriately managed to lower their risk of TdP.
Pharmacists thus can help improve the monitoring and management of QT
prolongation.
PMID- 29955465
TI - Evaluation of QTc prolongation and dosage effect with citalopram.
AB - Introduction: Recently, controversy has surrounded a 2011 Food and Drug
Administration warning against using citalopram at doses >40 mg/day due to QTc
prolonging effects. Methods: Patients >=18 years old at the VA North Texas Health
Care System were included in this retrospective review if they had received at
least 1 prescription for a 30-day supply of citalopram between January 1, 2007,
and February 29, 2012, and had a baseline electrocardiogram (ECG) within 1 year
before initiation or dose increase of citalopram and at least 1 repeat ECG within
3 months after citalopram initiation or dose increase. The primary endpoint was
the prevalence of QTc prolongation (QTc interval >=470 ms for men and >=480 ms
for women) after initiation or a dose increase of citalopram. For secondary
objectives, Fisher exact tests were used determine if there was a dose-dependent
difference in prevalence of QTc prolongation among the whole study sample and
among the subgroup of patients >=60 years old. Results: Among the entire study
sample, QTc prolongation was identified in 12 patients (16.4%) after initiation
or a dose increase of citalopram. In the subgroup of patients >=60 years old, QTc
prolongation was identified in 7 patients (21.9%). Prevalence of QTc prolongation
increased with dose in the entire study population (P = .016) and in patients
>=60 years (not significant). Discussion: This retrospective study suggests that
citalopram produces a dose-dependent increase in QTc interval.
PMID- 29955467
TI - Atypical antipsychotics: A review on the prevalence, monitoring, and management
of their metabolic and cardiovascular side effects.
AB - Introduction: Excessive weight gain, glucose intolerance, and dyslipidemia are
well-known physical side effects of the metabolic syndrome commonly associated
with atypical antipsychotic (AAP) treatment. We review these side effects of AAPs
and their monitoring and management strategies. Methods: A literature search was
conducted to identify articles published on the prevalence, monitoring, and
management of cardiometabolic side effects of AAPs. Results: Comparative risk of
AAPs on weight gain, hyperlipidemia, glucose intolerance, and QT interval
corrected for heart rate prolongation varies across the AAPs currently available.
Likewise, pharmacologic and nonpharmacologic options investigated for management
of these side effects, and monitoring those at appropriate intervals, differ
based on the clinical condition and risk factors identified. Discussion: Atypical
antipsychotics in general have little difference among them in short-term
efficacy; however, the prevalence of their physical side effects substantially
distinguishes them. It is of importance that clinicians carefully select AAPs
bearing in mind the presence of risk factors, initiating patients directly on
AAPs with a low risk of cardiometabolic side effects, and monitoring and managing
those side effects at appropriate intervals.
PMID- 29955468
TI - Management of antipsychotic-induced hyperprolactinemia.
AB - Introduction: Antipsychotics represent a large portion of the psychotropics that
may induce hyperprolactinemia. Clinical psychiatric pharmacists must be adept in
stratifying the relative risk of hyperprolactinemia among psychotropics,
identifying patient risk factors, recognizing differential diagnoses, and
recommending therapeutic alternatives and treatment strategies. High-potency,
typical antipsychotics are more likely to elevate prolactin although exceptions
to the rule exist. Methods: A literature search of PubMed and Google Scholar was
performed to identify English language articles on the treatment of antipsychotic
induced hyperprolactinemia in humans. Methodological rigor is summarized for
compiled studies in addition to feasibility and limitations of application to
clinical practice. Results: There is an absence of robust evidence for the
management of antipsychotic-induced hyperprolactinemia. Among the pharmacological
treatments studied, aripiprazole (switching or augmentation) possessed the
strongest evidence. Pharmacological treatments with less evidence encompassed
dose reduction, switching to lower potency antipsychotics, and adding dopamine
agonists. To date, no head-to-head studies have been published on the above
approaches. Discussion: Atypical antipsychotics with low affinity for dopamine
(D2) receptors, such as olanzapine, are logical alternatives for the patient
experiencing drug-induced hyperprolactinemia. When augmentation is clinically
preferred to switching, a viable option is the addition of a full or partial
dopamine agonist, such as bromocriptine or aripiprazole, respectively. Patient
specific risk of psychiatric decompensation and the severity of symptomatic
hyperprolactinemia should be weighed when formulating treatment strategies.
PMID- 29955469
TI - Sexual dysfunction in selective serotonin reuptake inhibitors (SSRIs) and
potential solutions: A narrative literature review.
AB - Sexual dysfunction is an underdiscussed adverse effect to selective serotonin
reuptake inhibitors (SSRIs) and may increase the risk for discontinuation and
nonadherence to antidepressant pharmacotherapy. Given the prevalence of
depression, health care providers should educate patients about SSRI-associated
sexual dysfunction in order to promote patient awareness and medication
adherence. This study evaluated primary literature from 1997 to 2015 to identify
SSRI-related sexual side effects, therapeutic alternatives, and treatment
strategies. The results indicate that paroxetine is associated with the greatest
rate of sexual dysfunction among the SSRIs. Potential alternatives to SSRI
treatment include bupropion, mirtazapine, vilazodone, vortioxetine, and serotonin
norepinephrine reuptake inhibitors. In the event that a subject responds solely
to SSRIs but experiences unwanted sexual side effects, bupropion may be added as
an adjunctive medication. Some limited evidence also suggests that saffron may
reduce some aspects of sexual dysfunction, excluding ability to reach orgasm.
PMID- 29955470
TI - Priapism and renal colic in a patient treated with duloxetine.
AB - Antidepressant medications are associated with a variety of genitourinary and
adverse sexual effects, such as urinary hesitation, priapism, and delayed
ejaculation. Here, we report a case of priapism and renal colic following
initiation of duloxetine in a patient with history of tolerated selective
serotonin reuptake inhibitor treatment. To our knowledge, this represents the
first report of priapism and renal colic associated with duloxetine use. This
case contributes to the current body of evidence describing adverse genitourinary
and sexual effects associated with antidepressant medications.
PMID- 29955471
TI - Drug-induced cognitive impairment: Effect of cardiovascular agents.
AB - Introduction: Cardiovascular agents can be associated with a negative effect on
cognition, especially in older adults, critically ill people, and those with
baseline cognitive impairment. Negative effect on cognition is commonly reported
as uncomplicated acute confusion and delirium and, less commonly, chronic
cognitive changes due to drug-induced depression and/or dementia. Methods: A
literature review of case reports, case series, prospective cohort studies,
clinical trials, and literature reviews were included in this study. Articles
were located using online databases PubMed and Medline using the following
keywords: antiarrhythmic agents, anticholinergic burden, antihypertensive agents,
beta-blockers, cardiovascular agents, cognitive impairment, delirium, cognition,
dementia, depression, digoxin, diuretics, and drug-induced cognitive impairment.
Results: In general, use of all antihypertensives, especially in the case of
polypharmacy or inappropriate dosing, can lead to hypotension and/or bradycardia,
and thus lead to mental/cognitive status change due to decreased cerebral
perfusion. Use of diuretics can be associated with fluid/electrolyte and/or acid
base imbalance, resulting in the onset of confusion and delirium. In addition,
cardiovascular agents with central bioavailability, such digoxin and select
antiarrhythmics, and antihypertensives may carry a risk for cognitive impairment
due to various mechanisms proposed, such as antagonism of central muscarinic
acetylcholine receptors, neurotransmission imbalance in the brain, and disruption
of physiologic function of sodium/potassium ATPase in the neuronal cells.
Discussion: When dealing with an individual who presents with acute, subacute,
and chronic changes in cognitive function, one should perform a thorough
medication history as the first step in order to aid in the identification of
drug-induced cognitive impairment.
PMID- 29955472
TI - Antimicrobial-induced cognitive side effects.
AB - Introduction: Antimicrobial-induced cognitive side effects are often overlooked
or underreported. Literature often reports symptoms of antimicrobial-induced
cognitive impairment under more general blanket terms, such as neuropsychiatric
side effects, neurotoxicity, or drug-induced delirium or encephalopathy. Methods:
A PubMed search using terms including antibiotics, antifungals, antivirals,
antimalarials, side effects, cognitive, neurotoxicity, encephalopathy, and
delirium was conducted. Respectively, symptoms of cognitive impairment were
teased out of the multiple neurologic complications presented for each case and
reported based on antimicrobial class. Articles were excluded if they focused
solely on neuropsychiatric side effects such as seizures, psychosis,
hallucinations, or mood disturbances, were conducted in animals, or involved
antiretroviral medication therapies. Results: Of over 50 case reviews, case
reports, retrospective chart reviews, and prospective cohort studies analyzed, 25
were deemed appropriate for purposes of this review. Common antimicrobial-induced
cognitive side effects for all antimicrobial classes included confusion,
delirium, encephalopathy, and impaired concentration or attention. Recurring risk
factors included, but were not limited to, older age and renal impairment.
Mechanisms of cognitive impairment were relatively specific to each antimicrobial
class. Discussion: Awareness of the potential for antimicrobial-induced cognitive
side effects, including the general time frame of symptom onset and symptom
presentation, is critical in challenging patient cases. This review article aims
to summarize the risk factors, clinical symptoms, mechanisms, and management of
antimicrobial-induced cognitive side effects. Pharmacists can play a key role in
prevention through adjustment of medications for renal or hepatic dysfunction,
avoidance of polypharmacy, and knowledge of critical drug interactions that may
precipitate cognitive decline.
PMID- 29955473
TI - A review on mortality risks associated with antipsychotic use in behavioral and
psychologic symptoms of dementia (BPSD).
AB - Introduction: As the population ages, the prevalence rate of behavioral and
psychologic symptoms of dementia (BPSD) rises, and there appears to be an
increasing need for pharmacologic treatment where nonpharmacologic treatment
would not suffice. Most clinicians are well aware of the increased risks of
cerebrovascular event and mortality from antipsychotic use in older adults with
dementia. Nevertheless, mortality risks reported in various publications still
vary considerably and lack consistency to allow direct comparison between
individual drugs. Methods: A literature search was conducted for primary and
secondary sources of evidence regarding the mortality risks associated with
antipsychotic use in BPSD. Results: Available evidence suggests that
antipsychotics are indeed associated with elevated risks of cerebrovascular
adverse events and mortality. There is also evidence suggestive of a varied risk
among individual agents, and a dose-response as well as a time-response
relationship. Discussion: This review aims to provide an updated overview of the
publications available on mortality data and risks associated with antipsychotic
dose and duration of use. Confounders and limitations are discussed to allow
clinicians to better make judgment calls on assessing risks and benefits when
treating BPSD with an antipsychotic.
PMID- 29955474
TI - Depression in the older adult: What should be considered?
AB - Introduction: The updated American Geriatrics Society (AGS) 2015 Beers Criteria
include the following antidepressant classes as potentially inappropriate
medications to be used with caution in older adults: selective serotonin reuptake
inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic
antidepressants, and mirtazapine. Methods: A search of the medical literature
using PubMed and references included in the AGS 2015 Beers Criteria. Results: The
treatment of depression in the older adult can additionally be complicated by
comorbid conditions, as 80% of older adults have at least 1 comorbid condition
and 50% have at least 2. These considerations limit the pharmacologic treatment
options for depression in older adults. However, the treatment of major
depression should not be overlooked, as it is quite common, with estimates of up
to 5% of older adults in the community and up to 13.5% in older adults who
receive home health care. Discussion: This article reviews treatment
considerations of depression in the older adult, including both available
screening tools and a discussion balancing the need for treatment of depression
in this population with the concerns addressed in the 2015 Beers Criteria.
PMID- 29955475
TI - Introduction to Parkinson disease (PD) and its complications.
AB - Parkinson disease (PD) is a common neurodegenerative disorder in older adults
characterized by motor and nonmotor symptoms and complications. Impulse control
disorders (ICDs), such as pathological gambling, compulsive shopping, compulsive
sexual behavior (hypersexuality), and binge eating disorder, affect 13.6% of the
PD population. Use of dopamine receptor agonists (DRAs) is considered a major
risk factor for ICD development. Amantadine and a high dose of levodopa were
linked to ICDs to a lesser extent than DRAs. Based on the severity of
behavior(s), ICDs can negatively impact social, professional, and familial lives
of patients and their families. Ideally, all PD patients taking DRAs, high doses
of levodopa, and/or amantadine should be routinely asked about or monitored for
ICDs during therapy initiation and continuation. Dose decrease or withdrawal of
the offending agent, primarily DRAs, is usually the most effective first step in
ICD management. Careful dose adjustment with close monitoring is warranted due to
risk for worsening of motor symptoms or emergence of dopamine agonist withdrawal
syndrome (DAWS). About 1/3 of PD patients with ICD who decrease or discontinue
DRA experienced DAWS. The lowest dose of DRA will need to be continued to balance
ICDs and DAWS as it is not alleviated by other dopaminergic or psychotropic
medications. Other therapies with low empiric evidence, such as amantadine,
naloxone, cognitive behavior therapy, deep brain stimulation, and
psychopharmacotherapy showed mixed results for ICD management. It is crucial that
clinicians are familiar with the psychiatric complications of PD, including ICDs,
beyond mere recognition and management of motor symptoms.
PMID- 29955476
TI - Factors to assess depression in homebound older adults.
AB - Introduction: The number of homebound older adults is expected to increase as the
elderly population grows. Many homebound older persons may be at high risk for
depression, which has been associated with adverse health outcomes. The objective
of this study was to identify selected factors that may predict depression in the
homebound older population. Methods: Data from 340 homebound adults, aged 65 and
older who were enrolled in Broward Meals on Wheels and who participated in a
telephone survey were analyzed. Participants were asked to report demographic
information, health status, medication-taking behaviors, mental health, and life
satisfaction. Multiple regression analysis was used to identify predictors of
depressed mood in this sample of older adults. Results: The majority of the
sample (aged 65-95 years; mean, 77 years) were female (76.5%), white (77.1%), and
living alone (52.6%). Multivariate modeling indicated that difficulty remembering
the number of prescribed medications to be taken, feeling groggy after taking
certain medications, poor self-reported health status, taking anxiety
medications, and less satisfaction with life explained 34% (adjusted R2) of the
variance in predicting depressed mood (F = 33.1, df = 5, P < .001). Discussion:
Multiple factors related to medication use were identified that may contribute to
higher levels of depressed mood in homebound older adults. These factors found in
our study may be used to create a screening model to be used by pharmacists to
identify homebound older adults who would benefit from further assessment for
depression.
PMID- 29955477
TI - Quantitative and economic analysis of clinical pharmacist interventions during
rounds in an acute care psychiatric hospital.
AB - Introduction: Clinical pharmacists have become an integral part of
multidisciplinary medical teams, including in the area of psychiatry. Previous
studies have shown that having pharmacists in multidisciplinary medical teams has
led to improved medication use, reduction of adverse drug events, and improved
patient outcomes. The purpose of this study is to conduct a quantitative and
economic analysis of the impact of clinical pharmacist interventions during
hospital rounds in an acute care psychiatric hospital setting. Methods: This is a
retrospective analysis of 200 clinical pharmacist interventions documented
between September 2013 and September 2014. Clinical pharmacist interventions were
classified into several categories and types. Only clinical pharmacist
interventions made during multidisciplinary team rounds were included in the
study. Descriptive statistics were used for the quantitative analysis of clinical
pharmacist interventions. The acceptance rate was calculated. Only the accepted
clinical interventions were included in the economic analysis. Economic outcome
involved an assessment of cost saving and cost avoidance. Results: The most
frequent types of clinical pharmacist interventions were discontinuation of
medications (38.5%), laboratory monitoring (26%), and medication order
modification (13.5%). The most common reason for drug discontinuation was
polypharmacy. Clinical pharmacist interventions were associated with a 92.5%
acceptance rate. Two hundred clinical pharmacist interventions were associated
with $6760.19 medication cost saving and $62 806.67 cost avoidance. Discussion:
Clinical pharmacist interventions during rounds in an acute care psychiatric
hospital setting mostly involve medication order modification and laboratory
monitoring. They are also associated with significant cost saving and cost
avoidance.
PMID- 29955478
TI - Evaluation of adherence in patients prescribed long-acting injectable
antipsychotics: A comparison of biweekly versus monthly administered
neuroleptics.
AB - Background: Long-acting injectable antipsychotics (LAIAs) have been developed to
decrease medication nonadherence. LAIAs are usually given biweekly or monthly,
with the exception of new 3-month and 6-week formulations. There has been no
known evaluation regarding whether the frequency of LAIA formulation affects
adherence. The purpose of this study is to evaluate whether there is a difference
in adherence between LAIAs administered biweekly or monthly. Methods: Eligible
participants were identified from the Louis Stokes Cleveland VA electronic
medical record as having an active prescription for a LAIA between September 1,
2009, and September 1, 2014. Participants were then evaluated using inclusion and
exclusion criteria to determine study entrance. Medication possession ratios
(MPRs) were calculated for each participant to determine adherence for comparison
of objectives. Descriptive statistics and t tests were used to identify
significant differences between groups. Results: There were 128 participants
enrolled based on eligibility criteria. There were no differences in MPRs for
biweekly versus monthly administered LAIAs (0.98 versus 0.97, respectively; P =
.691). No differences in adherence were observed between first- and second
generation LAIAs (0.98 versus 0.98, respectively; P = .975), or for risperidone
LAI versus paliperidone palmitate (0.97 versus 0.99, respectively; P = .269).
Hospitalizations were observed to decrease by 61% after LAIA initiation (P =
.021). Discussion: Based on the findings of this retrospective cohort review,
there was no difference in adherence in patients prescribed biweekly versus
monthly injected LAIAs. Patient preference and response, safety, tolerability,
cost, and availability of follow-up appointments should be other factors to take
into consideration for agent selection.
PMID- 29955479
TI - Impact on length of stay and readmission rates when converting oral to long
acting injectable antipsychotics in schizophrenia or schizoaffective disorder.
AB - Introduction: Nonadherence with oral antipsychotics in patients with
schizophrenia has been associated with symptom relapse and rehospitalizations,
resulting in increased morbidity and health care costs. Long-acting injectable
antipsychotics (LAIAs) are an alternative to enhance adherence and decrease
relapse requiring hospitalization. The objectives of this study are to determine
the impact of LAIAs on reducing length of stay, the rate of annual readmissions,
and the number of failed annual discharges (defined as a readmission in less than
30 days) in patients with schizophrenia or schizoaffective disorder admitted to
an acute inpatient psychiatric unit. Methods: Using the hospital database, 52
patients receiving a diagnosis of schizophrenia or schizoaffective disorders
treated with oral antipsychotics and later transitioned to LAIAs were evaluated
retrospectively. Results: Patients treated with LAIAs did not show a
statistically significant reduction in length of stay compared with their length
of stay on oral antipsychotics. Patients treated with LAIAs experienced a
statistically significant reduction in the rate of annual readmissions and a
reduction in the number of failed annual discharges, although the latter was not
statistically significant (P = .076 when compared to treatment with oral
antipsychotics). Discussion: These findings suggest a potential role for
maintaining patients with a diagnosis of schizophrenia or schizoaffective
disorder on LAIAs to prevent relapse and rehospitalizations. The reduction in the
number of failed annual discharges between the oral versus LAIA group, although
not statistically significant, warrants further investigation to determine the
impact of LAIAs on readmission within 30 days.
PMID- 29955480
TI - Evaluation of clinical pharmacy services within the primary care-mental health
integration model at the Tuscaloosa Veterans Affairs Medical Center.
AB - Introduction: The purpose of this review is to evaluate the direct delivery of
health care to veterans before and after incorporating clinical pharmacy services
within primary care mental health integration (PCMHI) at the Tuscaloosa Veterans
Affairs Medical Center. Prior to establishing the role of the clinical pharmacy
specialist (CPS) within PCMHI, the primary care providers deferred all mental
health assessments to specialty mental health. As the demands of the service grew
exponentially, assistance from clinical pharmacy was critical. Methods: A
randomized, computer-generated list of 114 patients selected for the
retrospective chart review was used to evaluate clinical outcomes in patients
enrolled in the PCMHI clinic 1 year preincorporation and postincorporation of
CPS. Outcome measures included the number of patients discharged from the PCMHI
clinic upon achieving therapeutic goals or discharged to specialty mental health
due to therapeutic failure or adverse drug events with first- and second-line
psychotropic agents. Results: When contrasting the end points, there was a 60%
increase in the number of patients who achieved therapeutic goal and a 32%
decrease in the number of patients discharged to specialty mental health clinic
postincorporation of CPS into PCMHI as compared to preincorporation of CPS (P =
.024). Discussion: The results support the significance of CPS in the PCMHI in
providing pharmacotherapy, patient education, and medication monitoring for
managing psychiatric conditions, such as depression, anxiety, and insomnia. In
addition, patients had greater accessibility to medication and frequent
monitoring and follow-up, ultimately improving patient outcomes.
PMID- 29955481
TI - Glycinergic signaling in the human nervous system: An overview of therapeutic
drug targets and clinical effects.
AB - Glycine and related endogenous compounds (d-serine, d-alanine, sarcosine) serve
critical roles in both excitatory and inhibitory neurotransmission and are
influenced by a multitude of enzymes and transporters, including glycine
transporter 1 and 2 (GlyT1 and GlyT2), d-amino acid oxidase (DAAO), serine
racemase (SRR), alanine-serine-cysteine transporter 1 (Asc-1), and kynurenine
aminotransferase (KAT). MEDLINE, Web of Science, and PsychINFO were searched for
relevant human trials of compounds. Many studies utilizing exogenous
administration of small molecule agonists of the glycineB site of n-methyl-d
aspartate receptor have been studied as have a growing number of glycine
transporter type 1 (GlyT1) inhibitors. The clinical effects of these compounds
are reviewed as are the potential effects of newer novel compounds.
PMID- 29955482
TI - Delta-9-tetrahydrocannabinol and cannabidiol: Separating the chemicals from the
"weed," a pharmacodynamic discussion.
AB - Cannabis is being increasingly used as a medical treatment for a variety of
illnesses. However, the cannabis plant has more than 70 different
phytocannabinoids with potential pharmacologic activity. Two of the most
researched phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and
cannabidiol (CBD). Evidence suggests CBD can decrease some of the psychomimetic
effects of THC. This has led to the development of a new drug, Nabiximols, for
the treatment of moderate to severe spasticity due to multiple sclerosis. A
discussion of evidence supporting proposed pharmacodynamic interplay between CBD
and THC is presented.
PMID- 29955483
TI - Brain-derived neurotrophic factor and schizophrenia.
AB - Schizophrenia is a severe disorder affecting approximately 1% of the population.
Historically, alterations of dopaminergic function were considered the primary
cause of schizophrenia. However, for many patients, drugs that alter dopaminergic
function do not consistently lead to resolution of the symptoms of schizophrenia.
Thus, there is an increased interest in pathophysiologic processes that result in
altered neurodevelopment and plasticity associated with schizophrenia. Brain
derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis,
synaptic plasticity, cognition, and neurotransmission. Genetic polymorphism,
expression, and function of BDNF have been implicated in psychiatric diseases,
including schizophrenia. This review discusses BDNF, its role in neurologic
processes, and the evidence implicating BDNF in schizophrenia.
PMID- 29955484
TI - Medical mimics: Differential diagnostic considerations for psychiatric symptoms.
AB - Patients with underlying medical disease can present to the health care system
with psychiatric symptoms predominating. Identification of an underlying medical
condition masquerading as a psychiatric disorder can be challenging for
clinicians, especially in patients with an existing psychiatric condition. The
term medical mimic or secondary psychosis has been used to describe this clinical
situation. Diagnostic categories from The Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition, that may encompass medical mimics include
substance-induced disorders, which includes medications, and unspecified mental
disorder due to another medical condition in situations where the clinician may
lack needed information for a complete diagnosis. At this time, there is no
single diagnostic test or procedure available to differentiate primary versus
secondary psychosis on the basis of psychopathology presentation alone. When
considering a diagnosis, clinicians should evaluate for the presence of atypical
features uncharacteristic of the psychiatric symptoms observed; this may include
changes in functionality and/or age of onset and symptom presentation severity.
The purpose of this work is to provide a structured clinical framework for
evaluation for medical mimics, identify groups considered to be at highest risk
for medical mimics, and present common syndromic features suggestive of a medical
mimic. Selected case scenarios are used to illustrate key concepts for evaluating
and assessing a patient presenting with acute psychiatric symptomatology to
improve judgment in ruling out potential medical causality.
PMID- 29955485
TI - Anti-NMDA receptor encephalitis: An emerging differential diagnosis in the
psychiatric community.
AB - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a new diagnosis, as
recent as 2007, that develops as a result of autoantibodies to the NMDA receptor.
The clinical manifestations of the disorder include complex psychiatric symptoms,
seizures, movement disorders, cognitive dysfunction, and autonomic instability.
Tumor resection, if present, and immunotherapy are the mainstays of therapy.
Treatment should be initiated early and aggressively as it has been associated
with better patient outcomes. A significant proportion of patients with anti-NMDA
receptor encephalitis initially seek the help of a psychiatrist, highlighting the
importance of its recognition within the mental health community. In an effort to
promote disease awareness, this article will review a patient case and the
pathophysiology, clinical presentation, diagnosis, and management of anti-NMDA
receptor encephalitis.
PMID- 29955486
TI - Acute psychosis secondary to suspected hyperparathyroidism: A case report and
literature review.
AB - Introduction: Hyperparathyroidism begins as a benign disease that is often left
undetected unless the patient presents with severe symptoms. Often, the first
sign of hyperparathyroidism is elevation in serum calcium. Case Description: A 38
year-old man presented with new onset acute psychosis. Laboratory testing
revealed co-occurring untreated hyperparathyroidism. Discussion: A literature
search was performed using PubMed to identify articles published in English with
the following key terms: "hyperparathyroidism," "psychosis," and "hypercalcemia."
A review of findings follows the case report. Despite a thorough literature
review, any pathophysiological explanation for psychiatric manifestations of
hyperparathyroidism remains hypothetical.
PMID- 29955487
TI - Evaluation of the use of low-dose quetiapine and the risk of metabolic
consequences: A retrospective review.
AB - Introduction: Quetiapine fumarate is an atypical antipsychotic approved for the
treatment of schizophrenia, major depressive disorder, and bipolar disorder. Due
to the sedative effects observed at low doses, prescribers use quetiapine to aid
patients with sleep disturbances. Current evidence has established that
quetiapine can cause negative changes in metabolic parameters, but it is unknown
if these consequences also occur at low doses. Due to the use of quetiapine for
sleep, the purpose of this study is to identify if metabolic effects are also a
risk with the use of low-dose quetiapine. Methods: Eligible subjects were
identified through the Veterans Affairs electronic medical records as having an
active prescription for quetiapine from June 30, 2012, through September 1, 2013.
Subjects were then evaluated using inclusion and exclusion criteria for
determination of study entrance. Descriptive statistics and t tests were utilized
to identify clinical and statistical differences in outcomes. Results: A total of
403 subjects were included in the final analysis. The average dose of quetiapine
was 116.8 mg and average duration of therapy was 44 months. Increases were
observed in systolic blood pressure (+1.95 mmHg; P = .036), diastolic blood
pressure (+1.97 mmHg; P = .001), body mass index (+0.52; P = .001), weight (+1.88
kg; P = .002), and fasting blood glucose (+6.71 mg/dL; P = .002). Conversely, a
decrease in total cholesterol (-10.06 mg/dL; P < .001) was recognized.
Discussion: As a result of the findings, there may be negative metabolic
consequences with the use of low-dose quetiapine. Routine prescribing of low
doses for sleep as a first-line medication should be avoided.
PMID- 29955488
TI - Mania possibly linked with bupropion for smoking cessation: A case report.
AB - Bupropion is an antidepressant thought to have a reduced risk of inducing mood
switching as compared to other antidepressants. Minimal information is available
on the induction of mood shifts when used for smoking cessation. This case
describes a 38-year-old female who experienced mania following initiation of
bupropion for smoking cessation. After completion of a thorough literature
search, this appears to be the first case report describing mania induced by
bupropion that was refractory to medications and was resolved with
electroconvulsive therapy. This case highlights the need for clinicians to
perform thorough histories of patients to avoid missing psychiatric history prior
to starting bupropion as well as monitor for changes in mood or behavior after
initiation of therapy.
PMID- 29955489
TI - Metabolic monitoring in children 5 years of age and younger prescribed second
generation antipsychotic medications.
AB - Introduction: The objective of this article was to identify the rates of patients
<=5 years of age who received recommended monitoring before and after second
generation antipsychotic (SGA) initiation and had an SGA metabolic adverse effect
(MAE). Methods: This was a retrospective cohort analysis conducted at Kaiser
Permanente Colorado, an integrated health care delivery system, between January
1, 2002, and June 30, 2011. Commercially insured patients <=5 years of age newly
initiated on an SGA were included. Patients were followed for up to 3 years.
Metabolic monitoring included lipid profile, blood glucose, blood pressure, and
weight measurements. Patient characteristics and outcomes were described using
descriptive statistics. Results: A total of 40 patients were included. Overall, 2
(5.0%) patients received all recommended baseline monitoring, and no (0.0%)
patients received all recommended follow-up monitoring. Weight monitoring was
completed most frequently with rates of completion of 57.5%, 95.0%, 85.0%, and
76.5% at baseline and years 1, 2, and 3, respectively. At least 1 MAE was
identified in 14/40 (35.0%), 5/28 (17.9%), and 2/17 (11.8%) patients during years
1, 2, and 3, respectively. The most frequent MAE identified was weight gain.
Among patients identified with at least 1 MAE, 4/14 (28.6%), 2/5 (40.0%), and 2/2
(100%) received a behavioral intervention during years 1, 2, and 3, respectively.
Discussion: Overall, baseline and follow-up metabolic monitoring were poor.
Future studies should focus on examining barriers to monitoring in order to
improve health care quality.
PMID- 29955490
TI - Topiramate in the treatment of Prader-Willi syndrome: A case report.
AB - Background: Prader-Willi syndrome (PWS), a neurologic disorder caused by a
mutation of chromosome 15, is characterized by such symptoms as hypotonia,
hypogonadism, hyperphagia, cognitive impairment, and difficult behaviors. One of
the most concerning symptoms is hyperphagia, which can lead to uncontrolled
obesity. Obesity is a major cause of increased morbidity and mortality in
patients with PWS; however, diagnosing PWS early in life improves the prognosis.
Case Summary: An 11-year-old African American boy with a past medical history
significant for PWS, attention deficit/hyperactivity disorder, oppositional
defiant disorder, obesity, and asthma was admitted after he became violent and
destructive at his foster home while trying to get food. The patient had a 28-day
stay on the children's crisis intervention unit where quetiapine was discontinued
and he was maintained on clonidine 0.1 mg 3 times daily, hydroxyzine 25 mg in the
morning and 50 mg at bedtime, montelukast 5 mg daily and titrated on
methylphenidate 10 mg in the morning and 5 mg in the afternoon, topiramate 100 mg
twice daily, and aripiprazole 10 mg twice daily. The patient displayed improved
behavior control and less food-related aggression; he denied any side effects of
medications. Discussion: This case demonstrates the positive effects of
topiramate for reducing aggression and demand for food in a child with PWS most
likely due to an increase in satiety. It is hard to definitively attribute the
positive response directly to topiramate. Further research should be conducted to
determine if topiramate is an effective treatment option in these individuals.
PMID- 29955491
TI - Enteral administration of protein supplement and valproate: A potential
pharmacokinetic interaction.
AB - Background: Valproic acid (VPA) and its derivatives are highly protein bound.
Certain highly protein bound medications (eg, phenytoin) have specific
administration instructions for patients on enteral nutrition supplements to
optimize absorption of the medication. Pharmacokinetic interactions between VPA
and enteral nutrition or protein supplements demonstrating impaired absorption
have not been published to date. Case Report: A patient receiving enteral VPA
syrup via percutaneous endoscopic gastrostomy tube experienced a clinically
significant decrease in serum concentration when enteral protein supplement was
initiated. Other sources of interactions were ruled out, and VPA serum
concentration increased when doses were separated from protein supplement by 2
hours. Discussion: This is the first published case of enteral protein
supplementation affecting absorption of enteral VPA. Enteral feeds are known to
interact with other highly protein bound medications, and clinical practice for
these medications may be used to guide administration when an interaction with
VPA is suspected. Conclusion: When using enteral protein supplements
concomitantly with enteral VPA, clinicians may consider separating doses to avoid
potential interaction or impaired absorption.
PMID- 29955492
TI - Valproate serum concentrations in patients with hypoalbuminemia and medical
complications.
AB - Introduction: Valproic acid (VPA) and its derivatives are highly protein bound
with free fraction increasing with dose and serum concentration. Consensus
guidelines regarding dose adjustment for hypoalbuminemia are not available.
Methods: A literature search was performed using PubMed to identify articles with
the following key terms: "valproate," "valproic acid," "protein binding,"
"albumin," and "hypoalbuminemia." We report our findings as well as 5 cases
involving pharmacokinetic impact of hypoalbuminemia on valproate. Results: A
previously published model for normalizing VPA serum concentration for
hypoalbuminemia in patients with epilepsy was compared to results for 5 cases (4
female, 1 male) in which VPA was used for psychiatric illness. Only 1 of the
cases had free serum concentrations in the range that would be expected with the
model. Free concentrations ranged from 22% to 83% with no clear relationship to
other factors (weight, age, serum creatinine, or dose). Female patients with
similar albumin had higher free fractions than the 1 male patient. Discussion:
Due to the variability in pharmacokinetic impact of hypoalbuminemia, it is
important to monitor patients closely for signs of VPA toxicity in cases
involving altered albumin levels. It would be prudent to use free serum VPA
concentrations when patients experience fluctuations in albumin or have
unexpected response to medication.
PMID- 29955493
TI - Ketamine for the treatment of major depressive disorder and bipolar depression: A
review of the literature.
AB - Introduction: Over the past decade, ketamine has been studied for major
depressive disorder and bipolar depression. Ketamine is believed to exert its
antidepressant properties through N-methyl-D-aspartate receptor antagonism.
Methods: Study authors completed a literature review of seven randomized
controlled trials of ketamine usage in major depressive disorder and bipolar
depression. Results: Ketamine demonstrated a statistically significant
improvement over placebo or midazolam in major depressive disorder. Ketamine also
exhibited a statistically significant improvement over placebo in bipolar
depression. Discussion: Ketamine has shown promise in quickly reducing symptoms
in patients with treatment resistant depression and bipolar depression. Using
ketamine may be helpful for patients that have exhausted other therapeutic
options.
PMID- 29955494
TI - Clinical potential of psilocybin as a treatment for mental health conditions.
AB - Psilocybin, a classic hallucinogen, is a chemical produced by more than 100
species of mushrooms worldwide. It has high affinity for several serotonin
receptors, including 5-HT1A, 5-HT2A, and 5-HT2C, located in numerous areas of the
brain, including the cerebral cortex and thalamus. With legislation introduced in
1992, more work is being done to further understand the implications of
psilocybin use in a number of disease states. Certain mental health disease
states and symptoms have been studied, including depressed mood, anxiety
disorders, obsessive-compulsive disorder, alcohol use disorder, and tobacco use
disorder. This article provides an in-depth review of the study design and
results of psilocybin in each of these conditions and discusses the clinical
potential for use.
PMID- 29955495
TI - Evidence for the use of "medical marijuana" in psychiatric and neurologic
disorders.
AB - Introduction: Cannabis is listed as a Schedule I substance under the Controlled
Substances Act of 1970, meaning the US federal government defines it as an
illegal drug that has high potential for abuse and no established medical use;
however, half of the states in the nation have enacted "medical marijuana" (MM)
laws. Clinicians must be aware of the evidence for and against the use of MM in
their patients who may consider using this substance. Methods: A PubMed database
search was performed using the text string: "Cannabis"[Mesh] OR "Marijuana
Abuse"[Mesh] OR "Medical Marijuana"[Mesh] OR "Marijuana Smoking"[Mesh] OR
"cannabi*" OR "tetrahydrocannabinol." The search was further limited to
randomized clinical trial publications in English on human subjects to identify
articles regarding the therapeutic use of phytocannabinoids for psychiatric and
neurologic disorders. Commercially available products (ie, dronabinol, nabilone,
nabiximols) and synthetic cannabinoids were excluded from the review. Results:
Publications were identified that included patients with dementia, multiple
sclerosis, Parkinson disease, Huntington disease, schizophrenia, social anxiety
disorder, depression, tobacco use disorder, and neuropathic pain. Discussion:
There is great variety concerning which medical conditions are approved for
treatment with MM for either palliative or therapeutic benefit, depending on the
state law. It is important to keep an evidence-based approach in mind, even with
substances considered to be illegal under US federal law. Clinicians must weigh
risks and benefits of the use of MM in their patients and should ensure that
patients have tried other treatment modalities with higher levels of evidence for
use when available and appropriate.
PMID- 29955497
TI - Lithium rechallenge after renal transplant.
AB - Mrs B is a 65-year-old, married, white woman with long-standing history of
bipolar disorder type I who achieved mood stability with chronic lithium
treatment. She developed end-stage renal disease, which was suspected to be the
result of chronic lithium exposure in the context of medical comorbidity, and
subsequently required renal transplantation. Following transplantation and
discontinuation of lithium, Mrs B was unable to achieve mood stability with
multiple medication trials and required more than 40 medical and psychiatric
hospitalizations with eventual transition to skilled nursing care. After much
discussion among the psychiatric treatment team, the patient, and her husband,
primary care provider, nephrologist, and renal transplant surgeon, the decision
was made to restart the patient on lithium given her previous treatment success.
The purpose of this case report is to discuss the use of lithium following renal
transplantation. In this case, a multidisciplinary approach was used to assist
the patient in carefully weighing the risks and benefits of her treatment
decisions. The consensus of the patient, her husband, and her providers was that
the benefit of mood stabilization outweighed the potential risks of renal
toxicity. Although treatment with lithium after renal transplant is not a first
line treatment option, this case illustrates that lithium could be considered in
certain cases.
PMID- 29955496
TI - Ayahuasca: An ancient sacrament for treatment of contemporary psychiatric
illness?
AB - Ayahuasca is a traditional psychoactive sacrament that's been used in Amazonian
shamanic rituals for hundreds of years. Ayahuasca is notorious for its
psychedelic properties produced from the combination of monoamine oxidase
inhibitors (MAOIs) found in the Banisteriopsis caapi vine and N-N
dimethyltryptamine from Psychotria viridis or Diplopterys cabrerana. Recently,
ritual use of ayahuasca has increased and garnered attention for its potential in
treating mental illnesses, such as substance use and depressive disorders. Due to
its MAOI properties, there are serious drug interactions that may be of concern
among patients who participate in ayahuasca use. The objectives of this paper are
to describe ayahuasca's pharmacology, potential drug interactions, and clinical
data for its treatment potential in psychiatric illness.
PMID- 29955498
TI - Venous thromboembolism following initiation of atypical antipsychotics in two
geriatric patients.
AB - Background: Although not formally highlighted as a risk factor in current
practice guidelines, several observational studies have reported a possible
association between antipsychotic use and development of venous thromboembolism
(VTE). However, it is unclear to what extent the risk is elevated. Case Report:
Described are 2 cases of VTE following recent initiation of second-generation
antipsychotics in elderly patients. Ms A was a 65-year-old woman with newly
diagnosed bipolar I disorder who was hospitalized for acute mania and psychosis.
She was treated with risperidone along with traditional mood stabilizers and
developed a pulmonary embolism shortly after treatment initiation. Ms B was a 77
year-old woman with newly diagnosed bipolar I disorder who was hospitalized for
depression and psychosis. She was treated with quetiapine and electroconvulsive
therapy and developed a pulmonary embolism and deep vein thrombosis within 2
months of starting treatment. Risk assessment tools were not able to definitively
predict the VTEs that developed in our patients. Conclusion: The association
between antipsychotic medication and VTE has shown the highest risk with atypical
antipsychotics, high dosages, and initiation within the past 3 months. Risk
assessment tools may assist in assessing the risk of VTE in patients on
antipsychotic therapy, although patients who are deemed by these tools to have
minimal risk can still develop a VTE. Discussing VTE risk with patients when
considering antipsychotic usage may help clinicians and patients safely determine
the most appropriate treatment for their psychiatric illnesses while mitigating
potential adverse effects.
PMID- 29955499
TI - Dysphagia with second-generation antipsychotics: A case report and review of the
literature.
AB - Background: All antipsychotics are associated with extrapyramidal symptoms (EPS).
These can present as dysphagia, esophageal dysmotility, or aspiration, all of
which may not be recognized as EPS. Case Report: A 62-year-old with
schizophrenia, prescribed olanzapine 5 mg daily, presented agitated and endorsed
difficulty swallowing. Speech therapy suggested her complaints were related to
either reflux or dysmotility. Esophageal manometry showed her lower esophageal
sphincter was not fully relaxing, and identified an esophagogastric junction
outflow obstruction. Despite therapeutic dilation, oral intake remained poor.
Following an increase in olanzapine, she developed EPS, her dysphagia worsened,
and she was choking on food. Following a switch to aripiprazole her EPS and
appetite improved, and she ceased complaining of dysphagia. Discussion: Dysphagia
has been reported with first- and second-generation antipsychotics. A review of
the second-generation antipsychotic literature identified case reports of
dysphagia with clozapine (n = 5), risperidone (n = 5), olanzapine (n = 2),
quetiapine (n = 2), aripiprazole (n = 1), and paliperidone (n = 1). Postulated
mechanisms of antipsychotic-induced dysphagia include that it may be an
extrapyramidal adverse reaction or related to anticholinergic effects of
antipsychotics. Management of dysphagia includes discontinuing the antipsychotic,
reducing the dose, dividing the dose, or switching to another antipsychotic.
Complications of dysphagia include airway obstruction (eg, choking, asphyxia),
aspiration pneumonia, and weight loss. Additional complications include
dehydration, malnutrition, and nonadherence to oral medications. Conclusion: It
is important to recognize symptoms of dysphagia and esophageal dysmotility in
antipsychotic-treated patients. Intervention is necessary to prevent
complications.
PMID- 29955500
TI - Drug-induced parkinsonism: A case report.
AB - Drug-induced parkinsonism is defined as the appearance of parkinsonism on
treatment with pharmaceutical agents. Symptoms typically manifest within a few
days, and 90% of cases emerge within 3 months. The patient was a 68-year-old
white man with a past psychiatric history significant for bipolar I versus
cyclothymic disorder. The patient presented with pressured speech, flight of
ideas, distractibility, delusions, and disorganized thinking. He was started on
risperidone and, due to a subclinical response, was cross-tapered from
risperidone to olanzapine, and divalproex was started. The patient was then given
paliperidone 234 mg long-acting injection (LAI) and a second loading dose of 156
mg 1 week later. The patient's cognitive and functional status subsequently
declined, all neuroleptics were discontinued, and he was diagnosed with drug
induced parkinsonism. After a complicated hospital course the patient died
approximately 5 months after the administration of paliperidone LAI. Although
there are several confounding factors, due to the temporal relationship of events
it is likely that paliperidone LAI was a contributing factor for the development
of severe parkinsonism. Practitioners should be cognizant of the potential long
term consequences of paliperidone LAI.
PMID- 29955501
TI - A survey of pharmacists' perceptions of the adequacy of their training for
addressing mental health-related medication issues.
AB - Introduction: The purpose of this study was to conduct a survey of North Carolina
pharmacists' perceptions of their pharmacy training in mental health-related
medication issues and how this influenced their perceived ability to address
these issues in the provision of pharmaceutical care to their patients. Methods:
A survey consisting of 17 questions was developed and emailed to licensed
pharmacists in North Carolina. Surveys that were returned were analyzed to see if
conclusions could be made regarding the pharmacists' perceptions about their
mental health-related medication training and its influence on their practice.
Results: A total of 848 pharmacists completed the survey (response rate of 7.9%).
Of the survey participants, 489 (58.2%) reported that pharmacy school training
adequately prepared them to provide basic pharmaceutical care to patients taking
mental health-related medications. However, 350 (41.4%) reported feeling less
comfortable providing medication counseling for mental health-related medications
compared to cardiac medications. Discussion: Despite the volume of prescriptions
that mental health-related medications represent in day-to-day practice, a
significant portion of licensed pharmacists responding to our survey indicate
that the emphasis on mental health in their training may have been inadequate.
PMID- 29955502
TI - Consumer satisfaction with National Alliance on Mental Illness written medicine
information.
AB - Introduction: Written medicine information (WMI) is a collection of facts for a
specific medication, and it helps facilitate patient understanding of medication
therapy. The primary objective of this study was to assess consumer satisfaction
with National Alliance on Mental Illness (NAMI) WMI. A secondary objective was to
assess health care professional satisfaction. Methods: National Alliance on
Mental Illness WMI and surveys were offered to consumers, health care
professionals, and trainees at 3 treatment centers with psychiatric services. All
adults who received medication counseling were eligible for inclusion. Survey
responses were evaluated using descriptive statistics. Results: Most consumers
(82.4%) and providers (74.5%) reported overall satisfaction with NAMI WMI.
Consumers were least satisfied with information on how to manage unwanted
effects, drug-drug interactions, and readability (9.5%, 14.9%, 41.9%
dissatisfaction). Discussion: Evaluation and feedback from consumers and health
care professionals may influence decisions to refine NAMI WMI to meet consumer
needs.
PMID- 29955503
TI - Cardiometabolic management in severe mental illness requiring an atypical
antipsychotic.
AB - Introduction: Cardiometabolic management was evaluated in patients with diabetes
and a severe mental illness that require treatment with an atypical
antipsychotic. Methods: Seventy-four patients with diabetes and a severe mental
illness treated with an atypical antipsychotic from the Fargo Veterans' Affairs
Health Care System were included in this retrospective study. Primary end points
analyzed the change in hemoglobin A1c (Hgb A1c), blood pressure, and low-density
lipoprotein (LDL) cholesterol 12 months prior to and 12 months following the
initiation of an atypical antipsychotic. Secondary end points evaluated changes
specific to clozapine and olanzapine. Additional secondary end points evaluated
the medication management for cardiometabolic disease prior to and following
atypical antipsychotic initiation. Results: In the 12 months following atypical
antipsychotic initiation, there were no statistically significant changes in
metabolic parameters. Mean Hgb A1c increased from 6.9% to 7.2% (P = .47), mean
systolic blood pressure decreased slightly from 132 to 127.8 mm Hg (P = .97),
mean diastolic blood pressure decreased slightly from 79.6 to 76.6 mm Hg (P =
.19), and mean LDL remained unchanged at 104.4 mg/dL (P = .92). Medications to
control cardiometabolic disease increased substantially following atypical
antipsychotic initiation; 35.1%, 39.2%, and 39.2% of patients were started on one
or more new antihyperglycemics, antihypertensives, and statins, respectively.
Discussion: Patients had a significant increase in prescriptions to manage
cardiometabolic disease in the 12 months following initiation of an atypical
antipsychotic. Although medications to manage cardiometabolic disease increased,
the actual metabolic parameters did not significantly change during the same time
period.
PMID- 29955504
TI - D-cycloserine in the treatment of posttraumatic stress disorder.
AB - Introduction: Posttraumatic stress disorder (PTSD) is a common and serious
psychiatric illness. Exposure therapy is a type of cognitive behavioral therapy
that is considered a first-line treatment option for PTSD. D-cycloserine (DCS)
enhances fear extinction/exposure therapy in patients with various anxiety
disorders, presumably via its N-methyl-D-aspartate receptor partial agonist
effects. The aim of this paper is to review the published literature regarding
the efficacy of DCS in the treatment of PTSD. Methods: A literature search for
placebo-controlled trials assessing the use of DCS as the primary study drug in
PTSD was conducted for trials published before June 2015 using PubMed, Ovid
International Pharmaceutical Abstracts, and www.clinicaltrials.gov. The search
terms were variations of "cycloserine" and "posttraumatic stress disorder."
Results: Seven clinical trials were analyzed, including 2 trials comparing DCS
with placebo as add-on treatment to ongoing stable pharmacotherapy and 5 trials
that compared DCS with placebo given prior to exposure therapy. D-cycloserine as
adjunctive therapy showed no benefit in 1 trial and limited benefit in the other.
As an enhancement of exposure therapy, DCS showed beneficial effects in 1 trial,
detrimental effects in 1 trial, and inconclusive effects in 3 trials. Discussion:
Current literature does not adequately support the use of DCS as adjunctive
therapy without psychotherapy, but limitations of the 2 studies that exist make
firm conclusions unfeasible. D-cycloserine might have a role in augmentation of
exposure therapy. Future studies should consider receptor selectivity,
administration time with respect to peak cerebrospinal fluid concentrations,
number of exposure therapy sessions, and dose.
PMID- 29955505
TI - Dosing strategies for switching from oral risperidone to paliperidone palmitate:
Effects on clinical outcomes.
AB - Introduction: There are currently no guidelines for switching patients from oral
risperidone to paliperidone palmitate (Invega Sustenna(r)). Furthermore, the
paliperidone long-acting injectable (LAI) package insert does not recommend
bridging with oral antipsychotics, which may result in inadequate serum
concentrations in patients on >=4 mg/d risperidone. Methods: This study evaluated
the effects of suboptimal dosing and bridging in patients switched from oral
risperidone to paliperidone LAI on hospitalization days, emergency department
(ED)/mental health urgent care visits, and no-shows/cancellations to mental
health appointments. Patients were categorized into optimal or suboptimal dosing
based on their loading and maintenance paliperidone doses. Patients on
risperidone >=4 mg/d were categorized as bridged if they received risperidone for
>=7 days after the first paliperidone injection. Results: There were no
significant differences in outcomes between optimally and suboptimally dosed
patients. There were statistically significant reductions in hospitalization days
in patients who were bridged compared with patients who were not bridged. There
were statistically significant reductions in hospitalization days and ED/mental
health urgent care visits after switching to paliperidone LAI. Discussion: The
results of this study indicate that bridging patients who are on >=4 mg/d
risperidone, when converting to paliperidone LAI, is associated with reductions
in hospitalization days. However, more research is required to determine the
optimal dose and duration of the bridge. The results also indicate that switching
patients from oral risperidone to paliperidone LAI, even if the dose is
suboptimal, is associated with reductions in hospitalization days and ED/mental
health urgent care visits.
PMID- 29955506
TI - Impact of a mental health clinical pharmacist on a primary care mental health
integration team.
AB - Introduction: Primary care mental health integration (PCMHI) teams function to
improve access and quality of integrative physical and mental health (MH) care
through a stepped care treatment approach. The project's primary objective was to
evaluate the impact a PCMHI clinical pharmacist made on treatment outcomes and
interventions. The secondary objective was to assess medication adherence rates.
Methods: An electronic medical record was used to identify PCMHI patient
referrals for medication management during an 8-month period. Patients were
included if they were at least 18 years old and referred for medication
management of depression, anxiety, posttraumatic stress disorder, or alcohol use
disorder. The scores for the Patient Health Questionnaire (PHQ-9), the
Generalized Anxiety Disorder Questionnaire (GAD-7), and the Posttraumatic Stress
Disorder Checklist (PCL-C) were recorded at baseline and weeks 4, 8, and 12
during treatment. Results: The analysis included 50 patients, which resulted in a
total of 156 contacts between July 2014 and March 2015. The mean change in PHQ-9,
GAD-7, and PCL-C scores at week 12 as compared to baseline were a decrease of 10
(95% confidence interval [CI], 6.2-13.8, P < .001), 8 (95% CI, 3.1-12.9, P =
.006), and 14.5 (95% CI, -17.3-46.3, P = .109), respectively. A total of 336
treatment interventions were made, and the overall medication adherence rate was
82.9%. Discussion: Medication management, provided by a clinical pharmacist, was
associated with a statistically and clinically significant improvement on several
MH disorder rating scale scores.
PMID- 29955507
TI - Efficacy of long-acting, injectable versus oral naltrexone for preventing
admissions for alcohol use disorder.
AB - Introduction: Approximately 17 million Americans and 300 000 veterans have an
alcohol use disorder (AUD). Both oral naltrexone (NTX) and long-acting,
injectable naltrexone (LAI NTX) are FDA-approved to treat AUD. LAI NTX is often
reserved for patients with adherence concerns due to considerable differences in
drug cost and administration requirements. To date, there are no randomized
trials comparing efficacy of LAI NTX to oral NTX. This retrospective cohort study
compared clinical outcomes in veterans treated with LAI NTX or oral NTX. Methods:
Health care utilization in veterans at 1 Veterans Affairs facility treated for
AUD with oral NTX and LAI NTX was compared. The primary outcome was 90-day
alcohol-related hospital admissions per patient (ARA90). Secondary outcomes
included 90-day outpatient clinic and emergency department visits and 30-day
alcohol-related admissions (ARA30). Inclusion criteria included first-time
prescription of NTX for AUD from January 1, 2015, through December 1, 2015.
Veterans receiving concurrent acamprosate or disulfiram were excluded. Results:
Seventy-nine patients were included with 65 in the oral NTX group and 14 in the
LAI NTX group. The ARA90 was 0.17 for the oral NTX group and 0.64 for the LAI NTX
group (P = .06). The oral NTX group had significantly fewer ARA30 than the LAI
NTX group (P < .01). Oral NTX also had significantly lower health care
utilization for all other parameters. Discussion: Oral NTX was associated with
lower health care utilization compared to LAI NTX in this veteran population.
This indicates that LAI NTX may not provide additional benefit justifying the
cost. This study had several limitations. Randomized trials comparing efficacy
between oral NTX and LAI NTX are needed.
PMID- 29955508
TI - Mental health pharmacists as interim prescribers.
AB - Introduction: Turnover leading to fluctuations in prescriber availability
presents many challenges, most notably in access to and continuity of care. In
2015, the Veterans Affairs Eastern Colorado Healthcare System (VA ECHCS)
experienced a period of significant mental health prescriber turnover leading to
patient utilization of psychiatric emergency services (PES) for nonemergent
medication management. The resulting increase in volume placed excessive stress
on PES prescribers. Mental health pharmacists have opportunities to provide
interim medication management while patients are between prescribers. Methods:
This study was a retrospective, cohort study of patients unassigned to an
outpatient mental health prescriber due to prescriber turnover, receiving care at
VA ECHCS between October 1, 2015, and February 28, 2016. The primary outcome was
the number of pharmacist interventions performed. Secondary outcomes characterize
the interventions performed and describe the change in the mean monthly volume of
patients presenting to PES. Results: In this veteran population, 152
interventions were performed in 81 unique patients. The most common intervention
was prescription renewals (80%). Interventions most commonly involved
antidepressants (28%), antipsychotics (10%), and mood stabilizers (10%). Before
initiation of the clinic, Denver VA PES experienced a mean of 300 monthly visits.
After clinic implementation, PES visits decreased significantly to a mean of 237
visits per month (P = .041). Discussion: The pharmacist interim prescriber clinic
was associated with a significant decrease in mean number of patients seen per
month in PES. The success of the clinic also contributed to interest by the
mental health service to expand clinical pharmacy services.
PMID- 29955509
TI - A pilot study evaluating the effectiveness of a medicines education group in a
mental health inpatient setting: A UK perspective.
AB - Introduction: It is estimated that up to 50% of medications for long-term
conditions are not taken as prescribed. In mental health conditions, poor
adherence leads to increased relapse, suicide rates, and hospitalizations. It is
recommended that health care professionals aim to elicit and address beliefs and
attitudes about medication, and to understand the patient's experience of taking
them, as these, among other factors, affect adherence rates. This study evaluated
a pilot trial of a medicines group for adult inpatients on an acute mental health
ward. Methods: This study comprises a pilot service evaluation of a medicines
education group through the descriptive analysis of data obtained using a
tailored outcome measure using validated experience and attitude measures. The
medicines education group was designed by a multidisciplinary team and focused on
eliciting perceptual and practical barriers to adherence, lived experience,
psychoeducation, and shared problem solving. The group was run during a period of
3 months and was compared to a baseline data set. Results: In total there were 35
medicine group attendees, there were 3 dropouts, and the outcome measure was
fully completed in 68% of cases, with only 4 refusing, indicating this pilot
evaluation was feasible and acceptable. Descriptive analysis found that on
average, group attendees reported a better understanding of the purpose and side
effects of their medication, and felt more involved in decisions about their
medicines compared with the baseline data set. Discussion: This pilot evaluation
found that running a novel medicines education group, targeting perceptual and
practical barriers to adherence, was acceptable to attendees and feasible to
deliver on an adult psychiatric inpatient unit.
PMID- 29955510
TI - Comparison of readmission data between different categories of antipsychotic
drugs at a state psychiatric hospital in Oregon.
AB - Introduction: This chart review utilizes readmission rates and mean time to
readmission as markers of drug efficacy to compare different categories of long
acting injectable antipsychotics (LAIAs), antipsychotic polypharmacy, and
clozapine to oral antipsychotic monotherapy (OM) at a state psychiatric hospital
in Oregon (Oregon State Hospital). Methods: Charts were reviewed for patients
discharged between October 20, 2011, and September 23, 2015, with a diagnosis of
schizophrenia spectrum or mood disorder. Admission dates, discharge dates, and
discharge antipsychotics were reviewed for each patient dating back to 1991.
Discharge antipsychotics were categorized into groupings of LAIAs, antipsychotic
polypharmacy, and clozapine and compared with OM to assess readmission data
within 1, 3, and 5 years of discharge. The primary end point was readmission
rate, measured as a percentage, and the secondary end point was mean time to
readmission (MTR), measured in days. Results: Of 1088 patients reviewed, there
were 2031 patient discharges associated with antipsychotic agents and 1258
readmissions. Patients discharged on LAIA monotherapy or clozapine generally had
a lower readmission rate, and patients discharged on antipsychotic polypharmacy
generally had a higher readmission rate. Statistical significance for these
findings varied over time frames and subgroup analyses. The most notable finding
for the secondary end point was a significantly shorter MTR for patients
discharged on clozapine for all diagnoses and the subgroup analysis of
schizoaffective disorder. Discussion: These results are only a reflection of the
patient population at this hospital, and additional reviews at other facilities
with different patient characteristics could clarify applicability to other
patient populations.
PMID- 29955511
TI - Outcomes of mental health pharmacist-managed electronic consults at a Veterans
Affairs health care system.
AB - Introduction: The demand for mental health services has increased as more
veterans have been diagnosed with-and sought care for-one or more mental health
conditions. Within the South Texas Veterans Health Care System (STVHCS),
providers may submit electronic consults (e-consults) to mental health clinical
pharmacy specialists for medication review and recommendations. These consults
aim to manage veterans with uncomplicated mental health conditions in primary
care, making specialty mental health providers more available for those who need
such services. Pharmacists have improved outcomes and access to care for
conditions such as diabetes and hypertension, but currently, there is limited
evidence demonstrating the impact of pharmacists in mental health. Methods: This
quality improvement project assessed the effectiveness of the e-consult service.
Information was collected through a retrospective chart review of STVHCS veterans
with the corresponding consult note placed in their chart from May 2014 through
December 2015. Numbers of recommendations implemented and veterans maintained in
primary care were analyzed as markers of effectiveness. Time and cost savings
were secondarily explored. Results: A total of 361 consults were submitted for
353 unique patients. Of the 322 patients included in analyses, a total of 301
unique patients (93.5%) were maintained in primary care for at least 3 months. Of
the 21 not maintained in primary care, 15 recommendations were implemented; of
those maintained in primary care, 271 recommendations were implemented.
Discussion: This service improves mental health care-and patient access-by
promoting successful management and maintenance of less complicated patients in
primary care.
PMID- 29955512
TI - Early detection of an atypical presentation of neuroleptic malignant syndrome: A
case report.
AB - Neuroleptic malignant syndrome (NMS), which is considered a neurologic emergency,
is believed to be caused by exposure to dopamine antagonist or withdrawal from a
dopamine agonist. This article reports a case of suspected atypical NMS in a
patient following rapid conversion of ziprasidone to risperidone without
titration. While the initial presentation did not fully meet the Diagnostic and
Statistical Manual of Mental Disorders, 5th edition, diagnostic features, a
sequential treatment strategy was initiated and the patient appropriately
responded to antipsychotic cessation in addition to combination therapy with
dantrolene and bromocriptine. Neuroleptic malignant syndrome diagnostic criteria,
treatment, and prognosis are discussed.
PMID- 29955513
TI - Melatonin supplementation for the prevention of hospital-associated delirium.
AB - Characterized by acute alterations in cognition or consciousness, delirium is a
transient neuropsychiatric syndrome that develops in a large percentage of
hospitalized patients. Delirium is a robust predictor of increased morbidity,
mortality, and health care costs, especially when diagnosed in the critical care
setting. Although the exact pathogenesis behind delirium has yet to be defined,
disturbances in the sleep-wake cycle are a core feature. Currently, no
pharmacologic interventions are recommended for delirium prophylaxis. Due to the
role of melatonin in regulating the sleep-wake cycle, its use in delirium has
been investigated in recent years. Objective data has shown altered serum levels
of melatonin and its precursor, tryptophan, in patients with delirium, further
suggesting a correlation between melatonin and delirium. This article examines
the available evidence and discusses considerations surrounding melatonin
supplementation for the prevention of hospital-associated delirium.
PMID- 29955514
TI - Essential oil of lavender in anxiety disorders: Ready for prime time?
AB - Anxiety disorders are some of the most common psychiatric disorders, with
potentially debilitating consequences on individual function. Existing
pharmacotherapies for anxiety disorders are limited by delay to therapeutic
effect, dependence, tolerance, withdrawal, and abuse potential. Therefore, safe
and evidence-based complementary or alternative therapies may be important allies
in the care of patients with anxiety disorders. Essential oils are lipophilic and
concentrated botanical extracts that exhibit many properties of drugs, although
they are not Food and Drug Administration approved and have limitations
characteristic of herbal preparations. Lavender essential oil has an extensive
anecdotal history of anxiolytic benefit that has recently been supported by
clinical efficacy studies. The 2 primary terpenoid constituents of lavender
essential oil, linalool and linalyl acetate, may produce an anxiolytic effect in
combination via inhibition of voltage-gated calcium channels, reduction of 5HT1A
receptor activity, and increased parasympathetic tone. The objectives of this
article are to provide a brief overview of lavender oil in aromatherapy, explore
variability in the constituents of lavender oil, summarize its pharmacology and
safety profile, as well as describe its body of research that has been conducted
for anxiety.
PMID- 29955515
TI - Psychiatric symptoms and synthetic cannabinoid use: Information for clinicians.
AB - Background: Limited treatment information is available when patients present with
psychotic symptoms secondary to synthetic cannabinoid (SC) use. Symptoms
associated with use are often indistinguishable from those encountered with a
primary mental illness and also include aggression, confusion, and anxiety. For
these patients, clinicians rely on physical presentation, symptom(s) onset, and
episode duration when evaluating patients. Patient History: An adult man was
involuntarily admitted to inpatient status secondary to reports of bizarre
behaviors that included paranoia and psychomotor agitation. Because of the
severity of the symptoms, he was unable to participate in the admission
assessment. On day 2, he reported having smoked a substance provided by a friend.
In addition, he admitted to previous SC use on 3 occasions, with each occasion
resulting in an involuntary admission to inpatient status. The course of this
admission was unremarkable. Conclusions: A brief overview of psychiatric signs
and symptoms of SC use and information to help clinicians are included. The
presentation of psychotic symptoms secondary to SC may be consistent with those
of psychosis or other substances of abuse. Because of the variability in the
symptoms produced by SC use, clinicians are encouraged to consider SC use in the
diagnostic evaluation.
PMID- 29955516
TI - Treatment-emergent hypomania possibly associated with over-the-counter
supplements.
AB - The use of complementary and alternative medicine (CAM) is gaining popularity in
the Western world. Among the general public, CAM is often perceived to be
associated with less stigma, fewer adverse effects, and may be more affordable. A
number of patients utilize CAM for the treatment of depression; however, as there
is limited scientific evidence, the safety profile of these supplements are
largely unknown. In this case, a 42-year-old man developed hypomania
approximately 1 week after S-adenosylmethionine (SAMe) and 5-hydroxytryptophan (5
HTP) therapy was initiated for depression. The combination of SAMe and 5-HTP can
potentially induce hypomanic episodes.
PMID- 29955517
TI - Clinical pearls of gender-affirming hormone therapy in transgender patients.
AB - Despite the growing visibility of transgender individuals in the mainstream
media, this population still encounters discrimination as well as many barriers
to receiving appropriate care. Of note, not all medical providers are familiar
with gender-affirming hormone treatment for transgender patients. Gender
affirming hormone treatment is used in transgender patients to reduce
characteristics of their natal sex and induce those of their desired sex.
Pharmacists have a potential role to make a positive impact by providing
information regarding gender-affirming hormone treatment. This article aims to
give an overview of the medications used in gender-affirming hormone treatment,
the desired effects caused by these medications, the expected timeline to
achieving these effects, and to provide information as to where these treatment
guidelines can be found.
PMID- 29955518
TI - The current status of transgender health education in doctor of pharmacy
curricula in North America.
AB - Doctor of pharmacy programs across the country strive to prepare culturally
competent pharmacy professionals who are trained to provide compassionate and
evidence-based care to a variety of patients. Within the Accreditation Council
for Pharmacy Education 2016 Standards and Key Elements for the Doctor of Pharmacy
Degree, pharmacy schools are charged with the task of developing professionals
who can identify and diminish health care disparities. Transgender persons
represent one of the most underrepresented and underserved communities within the
modern health care system, yet very little information is available for training
future pharmacists to care for the transgender community. A literature search
using the MeSH terms transgender persons or trans-sexualism and pharmacy
education was conducted, and it revealed 1 article published by Parkhill and
colleagues in the American Journal of Pharmacy Education. A Google(r) search of
the phrase "transgender education in pharmacy school" was conducted and produced
1 additional published article as well as an online transgender education program
launched in November 2016. The following commentary outlines the current
literature and practices that involve integration of transgender health education
into pharmacy schools in North America and a discussion on areas for future
study.
PMID- 29955519
TI - Psychiatric admission in adolescent transgender patients: A case series.
AB - Gender dysphoria is defined as a marked incongruence between one's natal gender
and gender identity that causes significant distress. It may be present in
children but often fades prior to puberty. Gender dysphoria is more likely to
persist into adulthood when present in adolescents. Due to the common occurrence
of psychiatric comorbidities, gender dysphoria is a contributing factor leading
to outpatient and inpatient psychiatric care in children and adolescents. There
is currently limited available literature on psychiatric hospitalization and
management in transgender adolescents. A PubMed search revealed no case reports
regarding psychiatric admission for transgender adolescents with comorbid
anxiety, depression, or suicidal ideation. Due to the lack of literature related
to psychiatric management of transgender adolescent patients, this case series
briefly describes the past medical history, pharmacotherapy, and discharge
diagnoses of 5 transgender adolescents admitted to an inpatient psychiatry unit.
In this case series, 4 of the 5 patients identified as female to male and ages
ranged from 13 to 17 years. All patients had a history of depressive symptoms
with suicidal ideation as the key factor prompting admission. All patients were
managed on psychotropic pharmacotherapy, and 3 of the 5 patients were on
pharmacotherapy related to gender transition. Anxiety, depression, and suicidal
ideation were common comorbidities leading to psychiatric hospitalization of
adolescent transgender patients in various stages of gender transitioning in this
case series.
PMID- 29955520
TI - Approach to the provision of transgender health care in a veteran population.
AB - Transgender patients often experience health disparities, including higher rates
of psychiatric comorbidity, tobacco and substance use disorders, higher suicide
risk, and reduced access and initiation of medical and mental health services. In
2011, the Department of Veterans Affairs (VA) health care system released a
directive outlining the provision of transgender health care services. Since
2011, the number of transgender veterans seeking services has increased. To
address these health care disparities and ensure competent comprehensive medical
and mental health care for this population, an interprofessional team
collaborated to develop the first formalized Transgender Healthcare Clinic at the
VA Loma Linda Medical Center. The team consisted of an endocrinologist, primary
care provider, clinical pharmacist, psychologist, and social worker. Each member
of the team plays a key role in the management of mental and medical health care
for transgender veterans. After implementation of the Transgender Healthcare
Clinic and its respective model for appointments, access to gender transition
related health care has improved and expanded. Although the role of the clinical
pharmacist is well established in this clinic, the addition of a psychiatric
pharmacist to the transgender health care team could improve patient care through
the integration of an expert understanding of behavioral and pharmacologic
aspects facing transgender individuals. The psychiatric pharmacist is trained
with the unique skill set required to address these concerns and facilitate the
optimal management of co-occurring mental illnesses commonly seen in this patient
population. Further research focusing on the integration of psychiatric
pharmacists into transgender health care teams is needed.
PMID- 29955521
TI - Student pharmacists' social distancing toward people with mental illness.
AB - Introduction: Findings from previous studies indicated patients with mental
illness feel pharmacists do not provide appropriate care. In addition, many
patients with mental illness report not having a strong relationship with their
pharmacist. The objective of this study was to determine the level of social
distance of student pharmacists toward patients with mental illness. Methods:
Student pharmacists completed an anonymous survey. Data were collected using the
Bogardus Social Distance Scale (SDS). Level and correlates of social distancing
were examined. Results: Incomplete surveys were excluded, resulting in 334
completed surveys. A total of 276 students (83%) had an SDS score >=14,
indicating social distancing. There was no statistical difference noted in social
distancing between students and year of training (P = .482). The greatest social
distancing was in relation to trusting someone with mental illness to "care for
their child," where less than 1 in 5 students (17%) were willing to do this. Most
students (88%) were willing to work or be neighbors with someone with mental
illness, indicating less social distancing in these domains. Regression analysis
indicated a significant change in sum score with knowing someone or having a
first-degree relative with mental illness. Discussion: Results indicate social
distancing is prominent among pharmacy students. Results may be used in the
future to help identify solutions for improving social distancing and increasing
pharmacy student interaction to patients with mental illness. Further training
related to mental illness may assist with decreasing social distancing among
pharmacy students.
PMID- 29955522
TI - Student engagement and perceptions of stigmatizing views in a mental health
focused collegiate organization.
AB - Introduction: While often unintentional, stigma associated with mental health
remains prevalent among health care professionals and is implicated in treatment
disparities between patients with and without mental disorders. Pharmacists and
pharmacy students have also been previously described as prone to discomfort
interacting with this population. The purpose of this study was to evaluate
stigma, student involvement in mental health activities, and student interest in
psychiatric pharmacy. Methods: An anonymous, voluntary online survey was open to
all student chapters in a mental health-focused professional organization. Sixty
five students from 19 chapters participated in the survey after consent was
obtained. Stigma and social distance survey items were adapted from previously
validated instruments. Descriptive statistics were used and correlations were
investigated using Spearman rank correlation. Results: Results indicated that
students had overall low stigma but more negative views related to disclosure of
one's own illness or to more personal interactions. Level of involvement was
unrelated to level of stigma, and perceived impact by nonleadership activities
was associated with lower stigma (P = .016). Shadowing pharmacists and community
service were frequently reported as most influential on student perceptions of
mental health (23% and 26%, respectively). Discussion: Students involved in a
mental health-focused organization had overall positive perceptions toward mental
illness. Student engagement in specific opportunities at any level may be more
influential than total number of activities participated in. Students have a
strong interest in pursuing extracurricular activities in mental health and
perceive interactions with patient contact as the most influential on their
attitudes.
PMID- 29955524
TI - Graphic representation of pharmacology: Development of an alternative model.
AB - Introduction: Providing clinicians with an easy to grasp and understandable
representation of pharmacology is important to allow optimal clinical decisions
to be made. Two of the most clinically relevant dimensions are receptor binding
affinity and functional activity. The binding affinity for an agonist is
described by the dissociation constant (KA ), and an antagonist by the inhibition
constant (Ki ). Functionally, medications can act as superagonists, agonists,
partial agonists, antagonists, partial inverse agonists, or inverse agonists at
several receptor sites, transporters, or ion channels. Comprehending the
differences between agents is complicated by the number and types of binding
sites. Methods: Binding and functional data are obtained from primary literature,
product labels, human cloned receptor binding, and other sources. Binding
affinities are converted into ratios relative to the putative primary receptor
for that category of agent. Antipsychotic binding is referenced to dopamine type
2 long (D2L) receptor binding. Binding affinity ratios (BARs) generate a 6-spoked
diagram, with D2L as the hub. The most avidly bound sites are the spokes, and the
disk diameter represents the BAR. Where functional data are available, they are
shown as a pie chart shading the binding site's disk. Results: Binding and
function diagrams are shown for the antipsychotics where binding data are
available and are compared to previous methods of pharmacologic comparisons of
antipsychotics. Discussion: Use of graphic models of psychotropic pharmacology
improves clinician comprehension and may serve as an aid to improve rational
therapeutics and patient outcomes.
PMID- 29955523
TI - Effects of a psychiatric clinical rotation on pharmacy students' attitudes toward
mental illness and the provision of pharmaceutical care to the mentally ill.
AB - Introduction: Previous studies have found ineffectiveness of psychiatric clinical
rotations to change pharmacy students' attitudes toward mental illness, but those
studies had various limitations that cast doubt on this conclusion. Methods:
Pharmacy students who participated in a psychiatric clinical rotation over a 2
year time frame were invited to complete a survey at the beginning and end of
their rotation. The survey included scales that measured attitudes toward
dangerousness, social distance, stigmatization, suicide prevention, and provision
of pharmaceutical care. Results: Forty-one (100%) students participated in the
study. Statistically significant positive changes in total scale scores from pre
rotation to post-rotation were seen in the areas of stigmatization toward
patients with schizophrenia (P = .02), attitudes toward suicide prevention (P =
.05), and provision of pharmaceutical care services to patients with
schizophrenia (P < .00001) and depression (P = .0006). There were no
statistically significant changes on the total scores of the other scales, but
there was a moderate improvement in stigmatization toward patients with
depression. Discussion: Pharmacy students' participation in a psychiatric
clinical rotation failed to have a major impact on their social distance from
mentally ill patients. Findings were mixed in regards to stigmatization of
mentally ill patients. However, pharmacy students' attitudes toward suicide
prevention and providing pharmaceutical care services to mentally ill patients
were significantly improved by participation in a psychiatric clinical rotation.
Preceptors in the clinical setting should consider including educational
techniques that address pharmacy students' attitudes toward mental illness, as
improvement in such attitudes may further enhance their willingness to provide
pharmaceutical care services.
PMID- 29955525
TI - Brexpiprazole: A review of a new treatment option for schizophrenia and major
depressive disorder.
AB - Brexpiprazole is an atypical antipsychotic that works as a partial agonist at
serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at
serotonin 5-hydroxytryptamine2A. It has US Food and Drug Administration approval
for monotherapy treatment of schizophrenia and adjunctive treatment to
antidepressants for major depressive disorder. Two phase-3 clinical trials
demonstrated efficacy and relatively fair tolerability with regard to adverse
effects for each indication. Akathisia was frequently reported in the major
depressive disorder trials but less so in the schizophrenia trials. Significant
increases in body weight and triglycerides were seen across all studies.
Brexpiprazole appears to be a viable option for treating an acute exacerbation of
schizophrenia requiring hospitalization or adjunctive treatment of major
depressive disorder in patients who showed an inadequate response to 1 to 3
antidepressants. Further clinical trials are warranted to determine the long-term
efficacy of brexpiprazole, and comparison trials would be beneficial to establish
its place in therapy.
PMID- 29955526
TI - What's new in multiple sclerosis?
AB - Introduction: Multiple sclerosis (MS) is a chronic disease state that affects and
disables many people each year. The most common clinical presentation is
relapsing-remitting MS (RRMS). In the past 7 years, new medications have been
approved for the treatment of RRMS, thereby providing more treatment options for
patients and providers. The purpose of this article is to provide an update on
medications for the treatment of MS that have been approved since January 2010.
Methods: A review was performed utilizing CenterWatch to search for medications
approved by the US Food and Drug Administration for the treatment of RRMS between
January 2010 and April 2017. The package inserts of medications indicated for
RRMS were analyzed, and key points were summarized. PubMed and EBSCOhost were
utilized to identify articles relevant to RRMS background and treatment. Results:
Seven medications with varying mechanisms of action have been approved to treat
RRMS since 2010. Pharmacotherapy options include oral and injectable
formulations. Efficacy across the agents is comparable, and each agent has safety
data from clinical trials. The safety profile varies between oral and injectable
agents, but potential adverse effects are important to consider before
initiation. Therapeutic selection is based on patient preference, dosing
(frequency and route), and safety considerations. Discussion: Multiple
therapeutic options are available for the treatment of RRMS. Health care
practitioners should be cognizant of the adverse effects, dosing route, and
frequency in order to optimally tailor therapy to meet individual patient needs.
PMID- 29955527
TI - Review of cariprazine in management of psychiatric illness.
AB - Schizophrenia and bipolar disorder are severe and debilitating psychiatric
disorders. Despite the availability of numerous antipsychotic drugs, many
patients still experience poor outcomes and treatment-limiting adverse side
effects. Cariprazine is a novel antipsychotic with unique pharmacodynamic and
pharmacokinetic properties. It is both a dopamine type 2 and dopamine type 3
partial agonist with 2 equipotent metabolites, desmethyl cariprazine and
didesmethyl cariprazine, of which didesmethyl cariprazine has a half-life of 1 to
3 weeks. The objective of this article is to review the literature regarding
efficacy and tolerability of cariprazine in the management of psychiatric
disorders to determine its current place in therapy.
PMID- 29955528
TI - Pimavanserin (NuplazidTM) for the treatment of Parkinson disease psychosis: A
review of the literature.
AB - Introduction: Pimavanserin (NuplazidTM) is an atypical antipsychotic currently
indicated for the treatment of hallucinations and delusions associated with
Parkinson disease psychosis. The antipsychotic effects of this new agent are
believed to occur via selective inverse agonist activity at serotonin 5-HT2a
receptors. Methods: Study authors completed a literature review of 2 published
randomized controlled trials of pimavanserin for the treatment of Parkinson
disease psychosis. The Food and Drug Administration Briefing Document by the
Psychopharmacologic Drugs Advisory Committee for the review of pimavanserin dated
March 29, 2016, was reviewed for additional information on 2 unpublished trials.
Results: Pimavanserin has demonstrated no worsening of motor symptoms of
Parkinson disease, but only 1 of 4 trials has shown consistent statistically
significant improvements in psychotic symptoms compared with placebo. Discussion:
Options for the treatment of Parkinson disease psychosis are limited. The
selective receptor profile of pimavanserin offers advantages for tolerability.
Further studies are warranted to better provide clinicians and patients with
information regarding the clinical utility of this agent.
PMID- 29955529
TI - Three clinical pearls in the treatment of patients with seizures and comorbid
psychiatric disorders.
AB - A strong association exists between epilepsy and psychiatric comorbidities,
especially depression, anxiety, attention deficit disorders, and psychosis. The
impact of psychotropic medications in lowering seizure threshold both directly
and indirectly, hypersensitivity reactions to antiepileptic and other
psychotropic medications, and how antiepileptic drugs affect psychiatric
disorders are explored through three patient cases. Ultimately, in selecting an
appropriate psychotropic medication for an individual with epilepsy and
psychiatric comorbidities, it is important to consider the clinical and quality
of-life impacts that a particular medication will have on that individual.
PMID- 29955531
TI - Medication management of bipolar disorder during the reproductive years.
AB - The management of bipolar disorder during reproductive years is a challenge to
both patient and clinician. The rapidly changing landscape of medical literature,
newly available medications, and implementation of the Pregnancy and Lactation
Labeling Final Rule by the Food and Drug Administration can be dizzying. This
article serves as a brief, practical guide on the use of medications for the
treatment of bipolar disorder before, during, and immediately after pregnancy.
Special focus is devoted to the risk-benefit analysis of using potentially
teratogenic medications during pregnancy. Availability and appropriateness of
various contraceptive methods and folic acid supplementation in combination with
mood stabilizers is also addressed. Every clinician managing bipolar disorder in
adult women should be knowledgeable of family planning resources and what to do
in the setting of unintended pregnancy.
PMID- 29955530
TI - Management of serious cardiac adverse effects of antipsychotic medications.
AB - The use of antipsychotic medications has now expanded to multiple mental health
conditions beyond schizophrenia. This has increased the overall population
exposure to these medications, which have been associated with both metabolic
changes and adverse cardiovascular effects. QTc prolongation, torsades de
pointes, sudden cardiac death, myocarditis, and cardiomyopathy are all very real
concerns that clinicians face on a regular basis. One must take these risks into
consideration when selecting antipsychotic therapy and also when determining
whether therapeutic changes and adjustments are necessary. This review examines a
number of cardiac-associated concerns, the role that antipsychotics may play in
contributing to these adverse events, and suggested management interventions.
PMID- 29955532
TI - Treatment of psychotic symptoms in patients with Parkinson disease.
AB - Persistent psychotic symptoms will develop in up to 60% of patients with
Parkinson disease (PD). The initial approach to the management of PD psychosis
(PDP) begins with addressing concurrent systemic conditions associated with
psychotic behavior, such as delirium, medical conditions (eg, infections),
psychiatric disorders (eg, major depression with psychotic symptoms, mania,
schizophrenia), and substance misuse or withdrawal. A review of current
medications is recommended, and medications that may trigger psychotic symptoms
should be eliminated. If possible, antiparkinson medications should be reduced to
the minimum therapeutic dose or discontinued in a sequential manner. Generally,
dose reduction or discontinuation of anticholinergics is attempted first,
followed by that of monoamine oxidase B inhibitors, amantadine, dopamine
agonists, catechol-O-methyltransferase inhibitors, and lastly carbidopa/levodopa.
The aim of antiparkinson medication dose reduction is to achieve a balance
between improving drug-related psychotic symptoms and not significantly worsening
the motor symptoms of PD. If additional measures are needed for chronic PDP
treatment, the use of second-generation antipsychotics, such as clozapine,
pimavanserin, or quetiapine, must be considered. The first-generation
antipsychotics (eg, fluphenazine, haloperidol) are not recommended. In the
patient with comorbid dementia, the addition of a cholinesterase inhibitor might
also be beneficial for PDP. The choice of agent is based on patient-specific
parameters, potential benefit, and side effects.
PMID- 29955533
TI - Evaluation of buprenorphine/naloxone dose and use of sedating supportive
medication on treatment outcomes in veterans with opioid use disorder.
AB - Introduction: This retrospective cohort study evaluated effects of
buprenorphine/naloxone dose and concomitant use of selected sedating medications
on treatment outcomes in patients with opioid use disorder. Methods: Patients
enrolled in the buprenorphine/naloxone clinic at the study institution from 2009
until April 2013 were included. There were no exclusion criteria. Part 1 assessed
treatment failure within 6 months and time to treatment failure with
buprenorphine doses >8 mg and <=8 mg. Part 2 assessed for treatment failure
within 6 months and time to treatment failure with use of selected sedating
medications. Sedating medications were cyproheptadine, hydroxyzine, quetiapine,
and trazodone. Treatment failure was defined as documentation of illicit opioid
use per patient report, urine drug screen showing opioid use, or patient lost to
follow-up. Results: There were 132 patients included in this study, but 163
separate encounters due to multiple enrollments. Treatment failure was
experienced within 6 months 51 times a patient was prescribed <=8 mg (66.2%) and
26 times a patient was prescribed >8 mg (33.8%) (P = .0005). Average time to
treatment failure was 5.1 months with <=8 mg and 8.4 months with >8 mg. The 48%
of patients who received sedating medications did not demonstrate any significant
differences in treatment response at 6 months (P = .2746) or time to treatment
failure (P = .2209). Discussion: Doses of buprenorphine/naloxone >8 mg
demonstrated better treatment response and prolonged time to treatment failure.
Concomitant sedating medications did not have a statistically significant effect
on treatment response or time to treatment failure.
PMID- 29955534
TI - A retrospective chart review of opioid represcribing following nonfatal overdose
at a Veterans Affairs hospital.
AB - Introduction: Opioid-related overdoses have risen despite extensive media
coverage and apparent awareness of this public health crisis. Emergency
department visits related to opioid use nearly tripled from 2004 to 2011.
Patients with mental illness are more likely to be prescribed opioids and have
higher rates of overdose. This retrospective chart review sought to determine if
opioid represcribing occurred after patients were treated for a nonfatal opioid
overdose (NFO) at a Veterans Affairs hospital. Methods: Patients who experienced
an NFO between 2009 and 2013 were included and charts reviewed until January 1,
2016. Review of the electronic medical record (EMR) was performed to determine if
and when opioids were again prescribed after NFO. Results: Fifty-six veterans met
the inclusion criteria. A new opioid prescription was issued to 82% of patients
within 3 months following the index NFO date. The average daily morphine
equivalent dose prescribed before (122 mg) and after (120 mg) NFO did not differ.
A subsequent opioid overdose event occurred in 25% of patients, and there was 1
fatal event. Only 1 patient had medication overdose on the problem list of their
EMR. Discussion: Despite experiencing NFO, veterans continued to be prescribed
opioids without significant changes in the drug or dose; some experienced
repeated overdose events, possibly due to poor communication and documentation of
NFO. Pharmacists can play a key role in clinical interventions and education of
patients and prescribers.
PMID- 29955535
TI - Implementation and results of a symptom-triggered opioid withdrawal protocol at a
Veterans Affairs medical center.
AB - Introduction: The Chillicothe Veterans Affairs Medical Center serves veterans
from southern Ohio, Kentucky, and West Virginia, where the rates of non-medical
opioid use are some of the highest in the nation. Prior to this project, there
was not a standardized practice for the treatment of veterans undergoing opioid
withdrawal at the facility. In May 2015, a symptom-triggered protocol was
initiated to improve the quality of care and decrease the length of
detoxification for veterans treated at the Chillicothe Veterans Affairs Medical
Center. Methods: This paper reflects a 2-phase project that took place from
August 2014 through June 2016. Phase 1 focused on the development of a symptom
triggered opioid withdrawal protocol using the Clinical Opiate Withdrawal Scale
for assessment and buprenorphine/naloxone or clonidine for treatment. Phase 2 was
a retrospective cohort analysis comparing outcomes between group 1, before
protocol initiation; group 2, after protocol initiation with clonidine; and group
3, after protocol initiation with buprenorphine/naloxone. The primary outcome
assessed was length of detoxification (in days). Secondary outcomes included
length of hospitalization (in days) for the index admission, outpatient substance
abuse treatment program participation rates, and opioid sobriety rates at 3
months after detoxification. Results: A statistically significant reduction in
the duration of detoxification days was detected after protocol initiation in
veterans who received buprenorphine/naloxone or clonidine in accordance with the
protocol. Discussion: This retrospective quality analysis supports the use of a
symptom-triggered opioid withdrawal protocol using the Clinical Opiate Withdrawal
Scale for assessment and clonidine or buprenorphine/naloxone for detoxification
treatment.
PMID- 29955536
TI - Successful bystander-administered intranasal naloxone reversal of opioid overdose
between two veterans: A case report.
AB - Opioid overdose-related morbidity and mortality remain one of the most pressing
public health crises. Overdose education and naloxone distribution have emerged
as an effective initiative for mitigating overdose deaths. This case highlights
areas of patient education essential to optimizing treatment outcome when using a
naloxone reversal kit. The patient is a 46-year-old white male with a past
medical history significant for opioid use disorder, alcohol use disorder,
stimulant use disorder, sedative-hypnotic use disorder, and posttraumatic stress
disorder. The patient received an intranasal naloxone kit during residential
substance abuse treatment. Five months later, the patient requested a new kit and
was asked about the disposition of his previous kit. The patient recounted how he
was telephoned to pick up an unconscious friend (and fellow veteran) from a
nonresidential location. Upon arrival, the patient recognized opioid products
near his friend and took steps to reverse the suspected opioid overdose with his
2 mg/2 mL naloxone intranasal kit. The reversal was successful, but many critical
rescue response steps were omitted. This case report may guide future changes to
educating patients on appropriate responses to opioid overdoses with naloxone. A
PubMed search located one other case report of successful naloxone reversal of
opioid overdose in the veteran population, which involved fentanyl sold as
heroin. In our case report, a veteran successfully used his naloxone kit to
reverse a suspected opioid overdose in another veteran, but he incompletely
provided the rescue response. This experience may influence content changes for
future overdose education and naloxone distribution training.
PMID- 29955537
TI - Assessment of pharmacists' self-reported preparedness to provide pharmacotherapy
services to individuals with psychiatric disorders.
AB - Introduction: The purpose of this study was to compare pharmacists' level of
training and/or experience in psychiatric pharmacy to (1) their self-perceived
preparedness to provide pharmacotherapy services to individuals with psychiatric
disorders and (2) barriers to providing pharmacotherapy services to individuals
with psychiatric disorders. Methods: This study used data from an Internet-based
questionnaire. Respondents were divided into 2 groups: group A completed the
Arizona Pharmacy Association's Psychiatric Certificate Program, and/or was board
certified in psychiatric pharmacy, and/or was a member of the College of
Psychiatric and Neurologic Pharmacists, and/or had completed a psychiatric
pharmacy residency; group B had no specialized training and/or experience in
psychiatric pharmacy. A Mann-Whitney U test was used to compare the scaled
responses for each group. Results: Compared with pharmacists without training
and/or experience in psychiatry (N = 235), respondents with specialized training
and/or experience in psychiatric pharmacy (N = 38) reported more frequent
interactions with patients with psychiatric disorders and provided more
counseling and drug information, monitoring for adverse drug reactions, screening
for treatment issues, and both pharmacologic and nonpharmacologic treatment
recommendations (P < .05). Pharmacists trained in psychiatry reported being more
prepared to provide all pharmacotherapy services (P < .003), except in addressing
nonadherence, utilizing online resources, and providing pharmacotherapy services
to patients with attention deficit hyperactivity disorder. They reported fewer
barriers to providing pharmacotherapy services (P < .005), except for time to
provide services, having a private consultation area, and reimbursement for
patient care activities. Discussion: This study found that responding pharmacists
without psychiatric training/experience may need additional education and
training after graduation and that they perceive more barriers in providing
services to the population with psychiatric disorders.
PMID- 29955539
TI - Surveys of substance use disorders education in US pharmacy programs.
AB - Introduction: Substance use disorders (SUDs) are a significant US health problem
affecting roughly 20 million Americans, but there continues to be limited access
to SUD treatment and inadequate addiction medicine training. Therefore, it is
important to understand how SUD education is being delivered to US health
professionals, including pharmacists. Methods: A recent survey of US pharmacy
programs' neuropsychiatry curricula was evaluated to identify any progress made
toward increasing SUD education since the last national survey in 2004 and
determine any remaining gaps between what is currently being taught and American
Association of Colleges of Pharmacy (AACP) curricular guidelines for SUD
education updated in 2010. A survey of psychiatric pharmacists, regarding what
they thought should be taught, was also evaluated and compared with the 2010 AACP
curricular guidelines. Results: Our survey of US pharmacy programs demonstrated
that 94% of programs reported teaching SUD content in 2014-15, which has
increased from 81% reported in a survey study from 2004. There was also an
increase for average hours of SUD didactic instruction, which increased from 2.2
hours in 2004 to 2.7 hours in 2015. The majority of members (84%) recommended at
least 2 hours of SUD instruction, and 27% recommended teaching >=4 hours.
Discussion: There was an overall increase in SUD instruction, but the average
hours taught still falls short of 2010 AACP curricular guideline recommendation
suggesting >=4 hours. Furthermore, a majority of the psychiatric pharmacists we
surveyed did not agree with the AACP curricular guideline recommendation because
only 27% of members recommended >=4 hours of SUD instruction, and the average
hours recommended was only 2.7 hours.
PMID- 29955538
TI - Survey highlights the need to expand offerings of introductory pharmacy practice
experiences in psychiatry and neurology: Benefits and example experiences.
AB - Introduction: Introductory pharmacy practice experiences (IPPEs) are 1
requirement schools and colleges of pharmacy must fulfill to meet accreditation
standards. The purpose of this manuscript is to report existing IPPEs in
psychiatry and neurology across the United States. Methods: Two separate
electronic surveys were administered to individual College of Psychiatric and
Neurologic Pharmacists members with board certification in psychiatric pharmacy
with an academic affiliation and academic institutions in the 2014-15 academic
year to assess the neuropsychiatric curriculum in pharmacy programs. Results
focusing on IPPEs were summarized using descriptive statistics. Results: Academic
institutional data reveal only 37.3% offered IPPEs in psychiatry, and 6.7%
offered neurology. The number of available IPPEs is low even if a program offered
an available rotation. The majority of College of Psychiatric and Neurologic
Pharmacists member respondents (69.9%) did not offer IPPEs in psychiatry in the
2014-15 academic year, and none offered an IPPE in neurology. More than half of
individual respondents feel their institution should increase IPPEs in psychiatry
and neurology in order to enhance their curriculum. Discussion: To expand IPPE
availability, pharmacy programs should increase early exposure of pharmacy
students to patients with psychiatric and neurologic conditions. Longitudinal
experiences may allow students to engage in hands-on experiences, which may
impact future career aspirations and reduce stigma. Current example IPPEs at the
authors' institutions are included to stimulate discussion and action among
readers on how IPPEs in these practice areas may be developed. Implementation of
IPPEs in psychiatry and neurology is needed for students to gain experience
working with these patients.
PMID- 29955540
TI - Cases in Psychiatry: A description of a multi-campus elective course for pharmacy
students.
AB - Cases in Psychiatry was a multi-campus elective course aimed to expand psychiatry
knowledge beyond the required course curriculum. The format of the class included
didactic course work, small group discussion of patient cases and article
evaluation, submission of written notes, debates, and script concordance test
questions delivered via a live online platform. Based on student assessment and
feedback at the end of the course, the elective course was determined to meet the
prespecified course objectives.
PMID- 29955541
TI - Outcomes comparison of long-acting injectable antipsychotic initiation in
treatment-naive veterans in the inpatient versus outpatient setting.
AB - Introduction: Long-acting injectable (LAI) antipsychotics have become an integral
component in the treatment of schizophrenia and other psychotic disorders. Long
acting injectables may be initiated in either the inpatient or outpatient
setting; however, there have been no studies to evaluate whether LAI treatment
initiation setting impacts patient outcomes. This study sought to assess whether
outcomes, specifically psychiatric hospitalization rates, time to
hospitalization, and adherence with injections, differed between patients started
on LAIs in the inpatient versus outpatient setting. Methods: The electronic
medical records of all veterans prescribed an LAI at the McGuire Veterans Affairs
Medical Center from September 2009 through September 2014 were reviewed in this
retrospective study. Veterans met inclusion criteria if they were prescribed an
LAI during the study period and were excluded if they had received an LAI prior
to September 2009 or if the LAI was started at an outside facility. Patients were
separated into treatment groups according to initiation location. The primary
outcomes included psychiatric hospitalization rates and time to hospitalization.
The secondary outcome measured the proportion of LAI injections received.
Results: Fifty-five LAI treatment-naive veterans were included in this study. No
statistically significant differences were found in psychiatric hospitalization
rates, time to hospitalization, or proportion of LAI injections received when
comparing the inpatient and outpatient treatment initiation groups. Discussion:
Psychiatric hospitalization rates, time to hospitalization, and adherence to LAIs
did not differ between the inpatient and outpatient treatment groups, suggesting
that treatment initiation location does not have an effect on patient outcomes.
PMID- 29955542
TI - Evaluation of provider response to positive depression screenings and physician
attitudes on integrating psychiatric pharmacist services in primary care
settings.
AB - Introduction: The aim of this study was to identify potential gaps in the
management of depression and assess the perceptions of primary care providers
(PCPs) toward integrating psychiatric pharmacists into primary care settings.
Method: This was a retrospective chart review of patients >=18 years of age seen
in primary care clinics in Los Angeles County with a documented annual health
screening (AHS) between January 1, 2015, through December 31, 2015. Primary
outcomes were number and percentage of patients screened for depression with
patient health questionnaire (PHQ) assessments, positive depression screenings,
and interventions made for positive depression screenings. Secondary outcomes
were PCPs' perceptions on management of depression, use of AHS, and roles for
psychiatric pharmacists through evaluation of provider survey. Results: Of the
patients who received an AHS (n = 6797), 63% received PHQ assessments. Of 145
individuals with a positive PHQ-2, 69% had a positive PHQ-9. Greater than 50% of
individuals with a positive PHQ-9 had no preexisting depression diagnosis.
Seventy-six percent of individuals with a positive PHQ-9 and 78% with reported
suicide ideation had no documented intervention. The majority of providers
reported there is a role for psychiatric pharmacists in primary care. Discussion:
Gaps in the management of depression were identified. Although depression
screenings were performed for the majority of individuals receiving an AHS, no
documented interventions were made for most of those individuals who screened
positive for depression. Primary care clinics could benefit from psychiatric
pharmacist involvement in depression screening and follow-up processes.
PMID- 29955543
TI - Diuretics: A possible keystone in upholding cognitive health.
AB - Introduction: Dementia encompasses diseases of progressive memory loss and
neurological alterations, including Alzheimer disease. Hypertension is one risk
factor proposed for development of Alzheimer disease. The objective is to
evaluate the current literature for use of diuretics in the prevention of
dementia. Methods: Literature was not considered if published before January 1,
2000, or after May 31, 2015. PubMed was used to locate sources. Four search terms
were used to find data: Alzheimer disease, antihypertensive agents, diuretics,
and dementia. Results: Four studies of efficacy of diuretic usage in the
prevention against dementia met criteria. Potassium-sparing diuretics displayed
risk reduction of Alzheimer disease and maintenance of cognitive function. Risk
reduction was demonstrated when used alone (adjusted hazard ratio [aHR] 0.09, 95%
confidence interval [CI] 0.01-0.41) as compared to use of other antihypertensives
without potassium-sparing diuretics (aHR 0.76, 95% CI 0.49-1.15). Other
antihypertensive drug classes did show some benefit, however. Diuretic and
angiotensin receptor blocker users had a lower Alzheimer disease risk versus
those with no antihypertensive use (hazard ratio 0.40, 95% CI 0.26-0.61) and
(hazard ratio 0.37, 95% CI 0.19-0.72), respectively. Additionally, thiazide
diuretics were also shown to reduce Alzheimer risk. Thiazide and potassium
sparing combination significantly reduced risk versus non-antihypertensive users
(aHR 0.63, 95% CI 0.42-0.94). Discussion: Available research demonstrates an
inverse association between diuretic use and the incident rate of dementia.
Specifically, this has been found with thiazide and potassium-sparing diuretics
when used alone or in combination. This review suggests that patients receiving
diuretics for hypertension may receive an added neuroprotective effect.
PMID- 29955544
TI - Outcomes of patient education practices to optimize the safe use of lithium: A
literature review.
AB - Introduction: Lithium is commonly used to treat various psychiatric disorders and
is particularly effective in the maintenance phase of bipolar disorder.
Unfortunately, this drug has a narrow therapeutic index and, if not monitored
regularly, can result in toxicity. Therefore, for lithium to be prescribed
safely, clinicians must ensure that patients are well educated on lithium
toxicity, its prevention, and symptom recognition. This article summarizes
studies that investigated lithium education strategies to help promote the safe
use of lithium. Methods: Four electronic databases were searched using key terms
and subject headings. Reference lists of relevant papers were also reviewed. The
search was limited to literature published in English, without year limits.
Eligible studies examined lithium patient education and the impact on patients'
knowledge of safe lithium use. Results: Of a total of 517 citations that were
retrieved from the electronic database search, 12 were selected for inclusion in
this review. Most of the studies included assessed the effect of lithium
education on various aspects of patients' knowledge, including but not limited
to, lithium toxicity. Of the studies assessing the correlation between lithium
knowledge and lithium levels, most demonstrated a positive correlation between
lithium knowledge and lithium levels that were more stable and within the higher
end of the recommended therapeutic range. Conclusions: Studies evaluating lithium
patient education and its effect on improving the safe use of lithium are
limited. Nevertheless, this literature review highlights that lithium patient
education is critical to promote its safe use.
PMID- 29955545
TI - Overcoming barriers to monitoring patients taking second-generation
antipsychotics.
AB - Introduction: Patients taking second-generation antipsychotics (SGAs) are at
increased risk of developing metabolic syndrome because of the side effect
profiles of these medications. A medication use evaluation (MUE) was conducted
and showed that baseline monitoring rates of metabolic parameters in patients
taking SGAs are low. A pharmacist-run metabolic syndrome monitoring clinic (MSMC)
is available to mental health (MH) outpatients; however, the clinic is underused
by providers. The purpose of this project was to increase baseline metabolic
syndrome monitoring rates in patients taking SGAs by implementing interventions
to overcome barriers to monitoring and to accessing the MSMC. Methods:
Appropriate tools to improve monitoring were obtained, and an electronic consult
for the MSMC was created. A presentation and pamphlet were developed to improve
awareness. Information about free patient transportation was obtained and
distributed. Efficacy was assessed by evaluating patient referrals to the clinic
before and after intervention, comparing baseline monitoring rates after
implementation with the MUE data, and administering an anonymous survey to
outpatient MH providers. Results: There was a 37.5% increase in overall referral
rates to the MSMC after intervention, but only 51.5% of patients attended
appointments as scheduled. Monitoring of vital signs increased, but monitoring of
laboratory parameters decreased. A total of 60% (9 of 15) of providers completed
a survey, of which one third indicated they still forget to refer patients to the
MSMC. Discussion: Overall, baseline metabolic monitoring rates remained low
despite implementing several interventions. Patient and provider outreach is
crucial for initiating and maintaining a successful metabolic monitoring system
for patients taking SGAs.
PMID- 29955546
TI - Evaluation of adherence and persistence with oral versus long-acting injectable
antipsychotics in patients with early psychosis.
AB - Introduction: Despite the theory that long-acting injectable (LAI) antipsychotics
should be more likely to improve adherence, reduce gaps in therapy, and prevent
relapse compared with oral antipsychotics, there is little published evidence on
this issue, specifically in patients with early psychosis. Methods: Patients with
a new diagnosis for a psychotic disorder between July 1, 2013, and August 31,
2014, were retrospectively evaluated during a 12-month duration. The primary
outcomes were adherence and persistence. Adherence was determined by proportion
of days with medication, and persistence was defined as zero gaps in medication
therapy. The secondary outcome was the number of times a psychiatric acute care
service was used. Patients were divided into 3 groups based on their
antipsychotic prescription history: oral only, LAI only, or both formulations at
separate times throughout the study period. Results: Forty-seven patients met
inclusion criteria. The average proportions of days with medication were 32%,
76%, and 75% for the oral, LAI, and both formulations groups, respectively (P <
.001). For medication persistence, there were 32 patients (91%), 3 patients
(75%), and 5 patients (63%) with at least 1 gap in therapy for the oral, LAI, and
both formulations groups, respectively (P = .098). For acute care services, there
was a median number of zero acute care visits for each of the 3 groups (P =
.179). A post hoc subgroup analysis found medication adherence to be
statistically different between the oral and LAI groups. Discussion: Long-acting
injectable antipsychotics were associated with better adherence compared with
oral antipsychotics in patients with early psychosis.
PMID- 29955547
TI - Assessing prescribing practices of clozapine before and after the implementation
of an updated risk evaluation and mitigation strategy.
AB - Introduction: Clozapine is an atypical antipsychotic medication approved for
treatment-resistant schizophrenia and suicidal behavior in schizophrenia or
schizoaffective disorders. Despite its therapeutic efficacy, clozapine is
associated with several adverse effects, including agranulocytosis. In late 2015,
the Food and Drug Administration updated the risk evaluation and mitigation
strategy (REMS) for clozapine with new requirements for monitoring, prescribing,
and dispensing. The purpose of this study was to evaluate clozapine prescribing
practices at a Kentucky state psychiatric hospital before and after the
implementation of the updated REMS program. Methods: The primary outcome of this
study was to evaluate clozapine prescribing practices by identifying the number
of patients on clozapine therapy in the 6 months pre and post updated REMS
implementation. Included in the study were patients at a Kentucky state
psychiatric hospital on clozapine therapy for the 24 months before the updated
REMS implementation and in the 6-month study period after the implementation. The
secondary objective of this study examined psychiatrist comfort level of
prescribing clozapine. Results: Since the implementation of the updated REMS
program, there has been an increased percentage of patients that were prescribed
clozapine at a Kentucky state psychiatric hospital. This increase was not
statistically significant (P = .2610). Discussion: The prescribing practices of
clozapine within this facility did not differ significantly comparing pre- and
post-REMS change in terms of number of patients prescribed clozapine, patient's
dose, and therapy duration. Data from this study contributes to the body of
knowledge evaluating this new standard of practice under the updated REMS.
PMID- 29955548
TI - Assessment of venous thromboembolism risk and initiation of appropriate
prophylaxis in psychiatric patients.
AB - Introduction: Venous thromboembolism (VTE) prophylaxis is not included among the
measures for the Inpatient Psychiatric Facilities Quality Reporting Program.
Evidence suggests that antipsychotic agents may be an independent risk factor for
the development of VTE; therefore, development of a VTE risk stratification tool
would improve the quality and safety of care for the psychiatric inpatient
population. This study aims to develop clinically relevant criteria to assess VTE
risk upon admission to an inpatient psychiatric hospital. Methods: This
retrospective, single-center cohort study enrolled patients in 2 cohorts from an
inpatient psychiatric hospital. Patients in cohort I with new-onset VTE diagnosis
during admission were identified through international classification of diseases
9 and 10 coding. Cohort II consisted of a random sample of 100 patients in a 3
month period. The percentage meeting criteria for prophylaxis in each cohort was
assessed utilizing both the Padua Prediction Score and a modified score. Results:
In cohorts I and II, 66.7% and 14% of patients, respectively, met criteria for
VTE prophylaxis utilizing the modified Padua Prediction Score. One patient
received VTE prophylaxis in each cohort, and the median time to VTE diagnosis in
cohort I was 42 days. In cohort I, the rate of VTE was 0.08% based on estimated
discharges in the 26-month period. This is less than the annual rate of 1% to
2.4% for nursing homes or postacute rehabilitation facilities. Discussion: We
recommend the implementation of clinical decision support to prompt
individualized reassessment of VTE risk when length of stay exceeds 30 days.
PMID- 29955549
TI - Valproic acid-induced hyperammonemia: Incidence, clinical significance, and
treatment management.
AB - Introduction: Valproic acid (VPA)-induced hyperammonemia poses several clinical
challenges in psychiatric medicine. The reported incidence of this adverse effect
varies widely across the literature. Furthermore, practitioners treat
hyperammonemia in asymptomatic patients although studies suggest this practice is
unnecessary. The purpose of this study is to evaluate if patients with VPA
induced hyperammonemia are appropriately identified for treatment based on their
symptom presentation as well as determine the most efficacious treatment approach
for VPA-induced hyperammonemia. Methods: This study was completed at a community
teaching hospital, and patients were retrospectively identified from June 1,
2011, to June 30, 2016, and included if they were admitted to a psychiatric unit,
received at least 1 dose of VPA, and had at least 1 ammonia level drawn during
admission. Hyperammonemia was defined as greater than 47 MUmol/L, and symptomatic
hyperammonemia was defined based on specific symptom presentation. The treatment
modality was successful if the ammonia level was within normal range at
discharge. Results: Of the 357 patients screened, 347 patients met all inclusion
criteria for analysis. The reported incidence of hyperammonemia was found to be
36% with 43.2% of those patients presenting with symptoms. Lactulose initiation
was the most common treatment modality chosen (48.7%). Discontinuation of VPA was
the most effective treatment (56.3% success rate). Discussion: The results
demonstrate that many patients with elevated ammonia levels are asymptomatic and
therefore, based on findings within the literature, may not require treatment.
Although lactulose was found to be the most common treatment initiated, the most
effective was discontinuation of VPA.
PMID- 29955550
TI - Review of pharmacotherapy for smoking cessation in patients with schizophrenia.
AB - Smoking cessation is a chronic issue surrounding individuals with schizophrenia.
It is estimated that up to 90% of patients diagnosed with schizophrenia smoke
cigarettes. The purpose of this article is to provide a nonsystematic review of
the efficacy of smoking cessation interventions as well as to explore the
potential neuropsychiatric adverse effects of these agents in patients with
schizophrenia. Eighteen studies were found and included in the review. Overall,
nicotine replacement therapy, bupropion, and varenicline have all proven their
effectiveness at either promoting smoking abstinence or a significant reduction
in cigarette use.
PMID- 29955551
TI - A review of medical marijuana for the treatment of posttraumatic stress disorder:
Real symptom re-leaf or just high hopes?
AB - Introduction: The incidence of posttraumatic stress disorder (PTSD) is common
within the population and even more so among veterans. Current medication
treatment is limited primarily to antidepressants. Such medicines have shown to
produce low remission rates and may require 9 patients to be treated for 1 to
have a response. Aside from the Veterans Affairs/Department of Defense
guidelines, other guidelines do not recommend pharmacotherapy as a first-line
option, particularly in the veteran population. Marijuana has been evaluated as
an alternative and novel treatment option with 16 states legalizing its use for
PTSD. Methods: A systematic search was conducted to evaluate the evidence for the
use of marijuana for PTSD. Studies for the review were included based on a
literature search from Ovid MEDLINE and Google Scholar. Results: Five studies
were identified that evaluated the use of marijuana for PTSD. One trial was
conducted in Israel and actively used marijuana. Three studies did not use
marijuana in the treatment arm but instead evaluated the effects postuse. A
retrospective chart review from New Mexico relied on patients to recall their
change in PTSD symptoms when using marijuana. Three studies concluded there might
be a benefit, but two discouraged its use. Although the two negative studies show
a statistical difference in worse PTSD outcomes, clinical significance is
unclear. Discussion: Conflicting data exist for the use of marijuana for PTSD;
however, current evidence is limited to anecdotal experiences, case reports, and
observational studies, making it difficult to make clinical recommendations.
PMID- 29955552
TI - Combination of venlafaxine and phentermine/topiramate induced psychosis: A case
report.
AB - Background: Various publications have noted increases in dopamine, specifically
in the mesolimbic region of the brain, to have a direct correlation to psychotic
like symptoms. Venlafaxine, a first-line medication for depression, inhibits the
reuptake of both serotonin and norepinephrine. Additionally, venlafaxine weakly
inhibits the reuptake of dopamine. Phentermine/topiramate (Qsymia(r)),
specifically the phentermine component, functions by blocking the dopamine and
norepinephrine transporter, similar to amphetamine. Case Report: A 40-year-old
Hispanic woman was admitted to the inpatient mental health unit based on reports
of delusional thinking and several attempts of self-harm. Past medical history
was significant for major depressive disorder, posttraumatic stress disorder,
anxiety, irritable bowel syndrome, and migraines. The patient was started on
venlafaxine (75 mg extended-release by mouth once daily) for depression
approximately 1 month prior to admission. Furthermore, the patient was restarted
on a previously prescribed medication, oral phentermine/topiramate for weight
loss, in combination with venlafaxine, approximately 1 week prior to the bizarre
behavior. The patient denied any psychosis or changes in behavior when
medications were taken individually prior to the combination. The patient was
treated with lurasidone (40 mg by mouth daily) with resolution of psychosis.
Discussion: A PubMed search revealed no current literature or case reports on
psychosis induced by the combination of venlafaxine and phentermine/topiramate.
Individual case reports of psychosis in patients on venlafaxine alone and the
phentermine component of phentermine/topiramate alone have been reported.
PMID- 29955553
TI - Effectiveness of a direct-to-consumer written health education program in the
reduction of benzodiazepine and sedative-hypnotic use in an elderly population at
a single Veterans Affairs medical center.
AB - Introduction: The use of benzodiazepines and sedative-hypnotics in the elderly is
associated with a significant risk of delirium, falls, fractures, cognitive
impairment, and motor vehicle accidents. This quality improvement project applies
a direct-to-consumer intervention to an elderly veteran population to reduce the
use of these medications. Methods: Patients aged 75 and older currently taking a
benzodiazepine and/or a sedative-hypnotic were included in the project. Direct-to
consumer education intervention letters were mailed to patients within 30 days of
their next appointment. Their providers were emailed a questionnaire after the
patient's appointment. Providers were asked if the letter prompted a conversation
regarding medication use, whether the provider initiated discussion regarding a
taper, and whether a specific taper plan was developed. Medical records were
reviewed to determine if a reduction in dose or discontinuation occurred.
Results: Fifty-nine direct-to-consumer education letters were mailed to the
patients. Follow-up questionnaires were e-mailed to 44 providers, and 27
providers responded. Twenty-two percent of patients had their benzodiazepine
and/or sedative hypnotic dose reduced or discontinued after their follow-up
appointment. Sixty-seven percent of veterans initiated a conversation with their
provider regarding their medication with 74% of providers discussing dose
reduction. Fifty-six percent of recipients developed a specific taper plan with
their provider. Discussion: The data from this project suggests that direct-to
consumer patient education can reduce the exposure to benzodiazepines and
sedative-hypnotics in an elderly veteran population. More data is needed on
larger populations to further explore the benefit of direct-to-consumer
interventions.
PMID- 29955554
TI - Impact of a clinical pharmacist-managed clinic in primary care mental health
integration at a Veterans Affairs health system.
AB - Introduction: The demand for mental health (MH) services has increased as more
veterans seek MH care. At the South Texas Veterans Health Care System, Primary
Care Mental Health Integration (PCMHI) was developed to manage patients with
uncomplicated MH conditions, including depression, anxiety, or posttraumatic
stress disorder (PTSD), within an interdisciplinary primary care (PC) team that
includes clinical pharmacy specialists (CPSs). Pharmacists have improved outcomes
and access to care for many chronic medical conditions, but limited data
demonstrate the impact of MH pharmacists within PC. Methods: This project
evaluated the impact of a PCMHI CPS clinic on managing patients with recent
antidepressant initiation and CPS clinic intake from September 2015 through
December 2016, including follow-up through January 2017. Markers used to evaluate
effectiveness of the service included the Patient Health Questionnaire-9 scores,
antidepressant medication possession ratio, number of emergency department visits
for MH-related concerns, patient engagement in concurrent psychotherapy, and
referrals to specialty MH providers. Results: A total of 196 unique patients had
intake with the PCMHI CPS in the time specified; 172 of these patients were
included in analyses. There were 155 patients maintained in PC. Average Patient
Health Questionnaire-9 scores decreased from 14.5 to 8.5, with 63 patients (46%)
achieving response and 42 patients (31%) achieving remission. The average
antidepressant medication possession ratio was 0.93 for all included patients.
Discussion: A PCMHI CPS successfully manages and maintains patients with
uncomplicated MH conditions in PC through evidence-based pharmacotherapy, as
evidenced by symptom improvement, medication adherence, and low rate of specialty
MH referrals.
PMID- 29955555
TI - Preliminary evaluation of the efficacy, safety, and costs associated with the
treatment of chronic pain with medical cannabis.
AB - Introduction: Medical cannabis (MC) is commonly claimed to be an effective
treatment for chronic or refractory pain. With interest in MC in the United
States growing, as evidenced by the 29 states and 3 US districts that now have
public MC programs, the need for clinical evidence supporting this claim has
never been greater. Methods: This was a retrospective, mirror-image study that
investigated MC's effectiveness in patients suffering from chronic pain
associated with qualifying conditions for MC in New York State. The primary
outcome was to compare European Quality of Life 5 Dimension Questionnaire (EQ-5D)
and Pain Quality Assessment Scale (PQAS) scores at baseline and 3 months post
therapy. The secondary outcomes included comparisons of monthly analgesic
prescription costs and opioid consumption pre- and post-therapy. Tolerability was
assessed by side effect incidence. Results: This investigation included 29
subjects. Quality of life and pain improved, measured by change in EQ-5D (Pre 36
Post 64, P < .0001) and change in PQAS paroxysmal (Pre 6.76 - Post 2.04, P <
.0001), surface (Pre 4.20 - Post 1.30, P < .0001), deep (Pre 5.87 - Post 2.03, P
< .0001), unpleasant (Pre "miserable" - Post "annoying", P < .0001). Adverse
effects were reported in 10% of subjects. Discussion: After 3 months treatment,
MC improved quality of life, reduced pain and opioid use, and lead to cost
savings. Large randomized clinical trials are warranted to further evaluate the
role of MC in the treatment of chronic pain.
PMID- 29955556
TI - Evaluating psychiatric outcomes associated with direct-acting antiviral treatment
in veterans with hepatitis C infection.
AB - Introduction: Approximately 70% of veterans with hepatitis C virus infection have
at least one psychiatric illness. The advent of direct-acting antiviral (DAA)
therapy provided an alternative to interferon-alpha regimens and revolutionized
treatment, however, the extent of psychiatric effects attributed to these agents
are unclear. The primary objective of this pilot study was to prospectively
analyze psychiatric outcomes, specifically depression, in veterans with hepatitis
C virus infection who are initiated on DAA therapy. Methods: In this single
center, prospective cohort study, psychiatric outcomes were analyzed using
Patient Health Questionnaire assessments at baseline and weeks 4, 8, and 12 of
complete DAA treatment. Outcome analysis were stratified based on specific DAA
therapy and preexisting mental illness (mental health [MH] subjects and non-MH
subjects), with a sub-analysis of major depressive disorder patients. Results:
Analysis included 48 patients, majority males (96%), with a mean age of 59.4
years (+/-8.0). Twenty-four (50%) patients had a preexisting MH diagnosis, with
major depressive disorder being the most common MH diagnosis (50%, n = 12).
Despite a trend toward improvement, no significant changes in questionnaire
scores after 12 weeks of DAA therapy were observed for all patient groups (P >
.05). Neither MH subjects nor non-MH subjects displayed a significant change in
questionnaire scores from baseline to end of treatment (P > .05). No patients
required acute psychiatric interventions during DAA treatment. Discussion:
Treatment with DAA therapy was not associated with psychiatric decompensation.
Data from this pilot study supports the safe utilization of DAA therapy in
hepatitis C virus patients with preexisting MH illness as it appears to be devoid
of depressive and psychiatric side effects.
PMID- 29955557
TI - Antipsychotic discontinuation after the initiation of selective serotonin
reuptake inhibitors therapy for the treatment of behavioral and psychological
symptoms associated with dementia.
AB - Introduction: Antipsychotics are used off label to treat behavioral and
psychological symptoms of dementia (BPSD). Due to the emerging data of selective
serotonin reuptake inhibitors (SSRIs) for treatment of BPSD, clinicians may
choose to use this medication class instead of antipsychotics when pharmacologic
therapy is necessary. The objective of this study was to evaluate the prevalence
of antipsychotic discontinuation 6 months after SSRI initiation for the treatment
of BPSD. Methods: Patients with Alzheimer dementia who were prescribed an
antipsychotic and later prescribed an SSRI for BPSD during January 1, 2009,
through December 30, 2014, were studied. Exclusion criteria included (1) a
dementia diagnosis besides Alzheimer; (2) scheduled benzodiazepines, mood
stabilizers, or non-SSRI antidepressant use during the study period; (3)
diagnoses of bipolar or psychotic disorders; and (4) diagnosis of delirium during
the study period. Patients' age, sex, race, and functional assessment of staging
for Alzheimer disease scores were collected. The names, doses, and stop dates of
SSRIs and antipsychotics were also recorded. Results: Thirty-six patients were
included in the analyses. Overall, antipsychotic use was reduced in 11 patients
(30.6%). Ten patients (27.8%) discontinued the antipsychotic, and 1 additional
patient had a reduction in dose. When comparing specific SSRIs, 8 (72%)
responders were prescribed citalopram, and 15 (60%) nonresponders were prescribed
sertraline. Discussion: Approximately 30% of patients with Alzheimer dementia who
were prescribed antipsychotics for BPSD were able to discontinue the medication
or had a dose reduction after starting SSRI therapy. Most SSRI responders were
prescribed citalopram.
PMID- 29955558
TI - Role of antidepressants in the treatment of adults with anorexia nervosa.
AB - Introduction: Anorexia nervosa (AN) is a severe psychiatric disorder that is
difficult to treat and is associated with frequent relapses and high mortality
rates. Psychiatric symptomatology (eg, depression, anxiety, obsessive-compulsive
disorder/behaviors) are common comorbidities. This review provides current
information about safety and efficacy of antidepressant therapy for management of
AN in adults. Methods: A literature review of randomized controlled trials, open
label studies, and case reports with adults or adults/adolescents was conducted.
PubMed and Medline were searched using anorexia management and treatment,
antidepressants, selective serotonin reuptake inhibitors (SSRIs), fluoxetine,
sertraline, citalopram, and mirtazapine in AN, relapse prevention in AN, and
psychotropic medications in AN. Results: The role and utility of antidepressants
in AN were published in double-blind, placebo-controlled studies; open-label
trials; and a retrospective study. Antidepressants should not be used as sole
therapy for AN although their use for confounding symptomatology makes discerning
efficacy difficult as they are given together with other therapies.
Neurobiological changes due to starvation and AN itself complicate results
interpretation. For safety, tricyclic antidepressants and monoamine oxidase
inhibitors are not recommended, and bupropion is contraindicated. Use of SSRIs
during acute treatment lacks efficacy. Use of SSRIs-primarily fluoxetine and to
some extent citalopram, sertraline, or mirtazapine-may aid in relapse prevention
and improvement of psychiatric symptomatology in weight-restored anorexic
patients. Discussion: Health care professionals should use clinical judgment
regarding fluoxetine or possibly citalopram, sertraline or mirtazapine as
adjunctive treatment to psychotherapy for relapse prevention, improvement of
depressive and anxiety symptoms, and/or obsessive-compulsive behaviors unresolved
with nutritional rehabilitation and psychotherapy.
PMID- 29955559
TI - Antiepileptic drugs and suicide-related outcomes in bipolar disorder: A
descriptive review of published data.
AB - Introduction: In January 2008 the US Food and Drug Administration issued a
warning to healthcare professionals about the potential for an increased risk of
suicidal thinking and behavior associated with antiepileptic drugs (AEDs). Given
that AEDs are important for treating bipolar disorder (BD), a better
understanding of suicide-related events is necessary. Methods: A PubMed search
was performed using the following search terms: anticonvulsant OR valpro* OR
carbamazepine OR lamotrigine OR oxcarbazepine OR topiramate AND bipolar AND
suicid*. The objective was to identify published investigations reporting rate
and/or risk data of suicide-related outcomes in BD patients treated with AED
monotherapy. Results: The search identified 323 reviewable citations, with 13 of
these studies (4.0%) being reviewed. Valproate was studied most often, and
lithium treatment was frequently used as a reference group. Carbamazepine and
lamotrigine had small treatment exposure durations. Suicide attempts and suicide
deaths were studied the most; a few trials investigated suicidal thinking and/or
hospitalizations for suicidal behavior. Suicide attempt rates occurred in the
following order: no treatment > carbamazepine > valproate > lithium, while
suicide death rates were: no treatment > valproate > lithium > carbamazepine. For
valproate, the risk of suicide attempts and suicide death appeared higher than
lithium, but lower than no treatment. Discussion: Investigating suicide-related
events for AEDs in BD is difficult; more data are necessary for valproate,
carbamazepine, and lamotrigine. An improved understanding of AED treatment and
suicide-related events in BD may help pharmacists become more effective at
supporting their patients with BD.
PMID- 29955560
TI - Levocarnitine for valproate-induced hyperammonemia in the psychiatric setting: A
case series and literature review.
AB - Introduction: Hyperammonemia is a potential adverse effect of valproic acid (VPA)
therapy, which is often asymptomatic but can lead to severe, life-threatening
encephalopathy. Carnitine deficiency due to VPA is the proposed mechanism for
hyperammonemia and the development of VPA-induced hyperammonemic encephalopathy
(VHE). Levocarnitine, the active form of carnitine, has been suggested for
treatment and prevention of VHE. Methods: Data was collected by chart review of 3
patients who received oral levocarnitine supplementation in the psychiatric
setting for VPA-induced hyperammonemia. Review of the literature was performed
through June 2017 using the following PubMed search terms: valproate, valproic
acid, hyperammonemia, altered mental status, encephalopathy, and levocarnitine.
Articles were included if they described use of levocarnitine in VPA-treated
patients with psychiatric disorders. Results: One patient developed
encephalopathy with resolution of symptoms after VPA discontinuation. Valproic
acid was restarted with the addition of levocarnitine to prevent VHE
reoccurrence. In the other 2 cases, levocarnitine was started prophylactically in
patients who developed hyperammonemia without emergence of any clinical symptoms.
Ammonia levels were reduced to normal in all cases, and no symptoms consistent
with encephalopathy were reported. The literature search identified 6 additional
cases with 5 of 6 reports supporting use of levocarnitine for decreased ammonia
levels as well as an observational trial. Discussion: This literature review and
case series illustrates successful use of levocarnitine supplementation for
reduction of ammonia levels in the setting of VPA-induced hyperammonemia among
patients with psychiatric disorders. However, clinical significance of ammonia
reduction in asymptomatic patients is difficult to determine.
PMID- 29955561
TI - A case report of guardian-consent forced paliperidone palmitate for behavioral
disturbance due to traumatic brain injury.
AB - Psychosis after traumatic brain injury (TBI) occurs in up to 10% of cases.
Although guideline consensus is lacking regarding drugs of choice for this
condition, current literature points to the use of atypical antipsychotics. This
case describes a 58-year-old male with major neurocognitive disorder due to TBI
with behavioral disturbance that was successfully treated with paliperidone
palmitate. In addition to the off-label use of paliperidone, this case also
explores the use of forced medication as the initial injection was given per
guardian consent. After completion of a literature review, this appears to be the
first case report describing the use of a long-acting antipsychotic for the
treatment of TBI-related psychosis. This case suggests that paliperidone
palmitate may be efficacious for psychosis following TBI; however, further study
is warranted.
PMID- 29955562
TI - Implementation and evaluation of Parkinson disease management in an outpatient
clinical pharmacist-run neurology telephone clinic.
AB - Parkinson disease (PD) is a progressive, debilitating neurodegenerative disease
that often requires complex pharmacologic treatment regimens. Prior to this
clinic, there was no involvement of a clinical pharmacy specialist (CPS) in the
outpatient neurology clinic at the West Palm Beach Veterans Affairs Medical
Center. This was a prospective, quality-improvement project to develop a clinical
pharmacist-run neurology telephone clinic and evaluate pharmacologic and
nonpharmacologic interventions in an effort to improve the quality of care for
patients with PD. Additionally, the CPS conducted medication education groups to
24 patients with PD and their caregivers, if applicable, at this medical center
with the purpose of promoting patient knowledge and medication awareness.
Medication management was performed via telephone rather than face to face. Only
patients with a concomitant mental health diagnosis for which they were receiving
at least one psychotropic medication were included for individual visits due to
the established scope of practice of the CPS being limited to mental health and
primary care medications. Data collection included patient and clinic
demographics as well as pharmacologic and nonpharmacologic interventions made for
patients enrolled from January 6, 2017, through March 31, 2017. A total of 49
pharmacologic and nonpharmacologic interventions were made for 10 patients. We
successfully implemented and evaluated a clinical pharmacist-run neurology
telephone clinic for patients with PD. Expansion of this clinic to patients with
various neurological disorders may improve access to care using an innovative
method of medication management expertise by a CPS.
PMID- 29955563
TI - Cross-kymography analysis to simultaneously quantify the function and morphology
of the archaellum.
AB - In many microorganisms helical structures are important for motility, e.g.,
bacterial flagella and kink propagation in Spiroplasma eriocheiris. Motile
archaea also form a helical-shaped filament called the 'archaellum' that is
functionally equivalent to the bacterial flagellum, but structurally resembles
type IV pili. The archaellum motor consists of 6-8 proteins called fla accessory
genes, and the filament assembly is driven by ATP hydrolysis at catalytic sites
in FlaI. Remarkably, previous research using a dark-field microscopy showed that
right-handed filaments propelled archaeal cells forwards or backwards by
clockwise or counterclockwise rotation, respectively. However, the shape and
rotational rate of the archaellum during swimming remained unclear, due to the
low signal and lack of temporal resolution. Additionally, the structure and the
motor properties of the archaellum and bacterial flagellum have not been
precisely determined during swimming because they move freely in three
dimensional space. Recently, we developed an advanced method called "cross
kymography analysis", which enables us to be a long-term observation and
simultaneously quantify the function and morphology of helical structures using a
total internal reflection fluorescence microscope. In this review, we introduce
the basic idea of this analysis, and summarize the latest information in
structural and functional characterization of the archaellum motor.
PMID- 29955564
TI - Comparison of brain monoamine content in three populations of Lymnaea that
correlates with taste-aversive learning ability.
AB - To find a causal mechanism of learning and memory is a heuristically important
topic in neuroscience. In the pond snail Lymnaea stagnalis, the following
experimental facts have accrued regarding a classical conditioning procedure
known as conditioned taste aversion (CTA): (1) one-day food-deprived Dutch snails
have superior CTA memory formation; (2) the one-day food-deprived snails have a
low monoamine content (e.g., serotonin, dopamine, octopamine) in their central
nervous system (CNS); (3) fed or five-day food-deprived snails have poorer CTA
memory and a higher monoamine content; (4) the Dutch snails form better CTA
memory than the Canadian TC1 strain; and, (5) the F1 cross snails between the
Dutch and Canadian TC1 strains also form poor CTA memory. Here, in one-day food
deprived snails, we measured the monoamine content in the CNSs of the 3
populations. In most instances, the monoamine content of the Dutch strain was
lower than in the other two populations. The F1 cross snails had the highest
monoamine content. A lower monoamine content is correlated with the better CTA
memory formation.
PMID- 29955565
TI - Single-molecular and ensemble-level oscillations of cyanobacterial circadian
clock.
AB - When three cyanobacterial proteins, KaiA, KaiB, and KaiC, are incubated with ATP
in vitro, the phosphorylation level of KaiC hexamers shows stable oscillation
with approximately 24 h period. In order to understand this KaiABC clockwork, we
need to analyze both the macroscopic synchronization of a large number of KaiC
hexamers and the microscopic reactions and structural changes in individual KaiC
molecules. In the present paper, we explain two coarse-grained theoretical
models, the many-molecule (MM) model and the single-molecule (SM) model, to
bridge the gap between macroscopic and microscopic understandings. In the
simulation results with these models, ATP hydrolysis in the CI domain of KaiC
hexamers drives oscillation of individual KaiC hexamers and the ATP hydrolysis is
necessary for synchronizing oscillations of a large number of KaiC hexamers.
Sensitive temperature dependence of the lifetime of the ADP bound state in the CI
domain makes the oscillation period temperature insensitive. ATPase activity is
correlated to the frequency of phosphorylation oscillation in the single molecule
of KaiC hexamer, which should be the origin of the observed ensemble-level
correlation between the ATPase activity and the frequency of phosphorylation
oscillation. Thus, the simulation results with the MM and SM models suggest that
ATP hydrolysis stochastically occurring in each CI domain of individual KaiC
hexamers is a key process for oscillatory behaviors of the ensemble of many KaiC
hexamers.
PMID- 29955566
TI - Arthroscopic Pectoralis Minor Release.
AB - The scapula has long been recognized as a key component in shoulder motion and a
crucial part of the kinetic chain connecting the body's core and upper extremity.
The pectoralis minor (PM) has garnered increasing attention as we better
understand scapular kinematics and its role in shoulder pain and dysfunction.
This is particularly important in patients with scapular dyskinesis and
especially in overhead throwing athletes. The most of these patients achieve
their recovery goals through nonoperative management, stretching, and
strengthening protocols; however, some patients do not respond to nonoperative
modalities. Several studies have recently shown improvement in shoulder motion
and outcome scores after open surgical release of the PM from its scapular
attachment. Arthroscopic release of the PM can be accomplished in the lateral
decubitus position with standard shoulder arthroscopic portals.
PMID- 29955567
TI - Reverse Microfracture of the Hip Acetabulum: A Technique for the Wave Lesion.
AB - The long-term efficacy of the treatment of chondral lesions is very important to
prevent hip osteoarthritis. Microfracture, autologous chondrocyte
transplantation, and direct chondral repair, among others, are techniques that
have shown good results in some cases. We propose a technique to treat wave
lesions through reverse microfracture, with bubble decompression and adherence of
the natural scar from the detached cartilage.
PMID- 29955568
TI - Arthroscopic Bone Graft Procedure Combined With Arthroscopic Subscapularis
Augmentation for Recurrent Anterior Instability With Glenoid Bone Defect.
AB - Glenoid bone loss and capsular deficiency represent critical points of
arthroscopic Bankart repair failures. The purpose of this Technical Note is to
present an all-arthroscopic bone block procedure associated with arthroscopic
subscapularis augmentation for treating glenohumeral instability with glenoid
bone loss and anterior capsulolabral deficiency. Two glenoid tunnels are set up
from the posterior to the anterior side using a dedicated bone block guide, and 4
buttons are used to fix the graft to the glenoid. The subscapularis tenodesis is
performed using a suture tape anchor. This combined arthroscopic technique (bone
block associated with arthroscopic subscapularis augmentation) could be a valid
and safe alternative to the arthroscopic or open Latarjet procedures.
PMID- 29955569
TI - Arthroscopic Massive Rotator Cuff Repair and Techniques for Mobilization.
AB - Massive rotator cuff tears, as classified by size or tendon involvement, are
challenging to repair due to scarring, retraction of the tendons, and difficult
visualization. Left untreated, these injuries can lead to fatty infiltration and
reduced acromiohumeral distance that precludes future repair. The high rate of
failure in these patients often impedes an anatomical repair. However, advanced
mobilization techniques of the supraspinatus help facilitate a reduction of an
otherwise irreparable tear. By performing this repair, more costly procedures may
be avoided, such as a superior capsular reconstruction and reverse total shoulder
arthroplasty. This Technical Note presents our preferred technique of an all
arthroscopic, medialized repair with double interval slides for the treatment of
a massive rotator cuff tear.
PMID- 29955570
TI - Single Portal Technique for Subscapularis Tendon Repair.
AB - The fast and steady development of arthroscopy techniques in the last couple of
decades led to a drastic increase of arthroscopic rotator cuff repairs over the
open procedure. Supraspinatus tears are the most common of all, but the
subscapularis tendon tear is a more common injury than expected. Most of the time
it presents as a partial tear or is associated with a subsequent rotator cuff
tendon injury, especially the supraspinatus. Nowadays, the standard procedure to
repair the subscapularis tendon is performed arthroscopically, even though a real
superior result over the open repair it is yet to be reported. Ideally less
operative time, less scarring, and postoperative pain would be the expected
benefits, but no study has compared the long-term outcome of these 2 procedures
yet. To maximize possible improvements, we would like to present an arthroscopic
technique: a subscapularis tendon repair performed with the aid of an angled
suture passer and using a single anterior working portal.
PMID- 29955571
TI - Frailty in elderly ICU patients in Greece: a prospective, observational study.
AB - Background: Of particular interest is the study of frailty syndrome in older
patients in recent years. This syndrome is characterized by weight loss and
muscle mass, a change in eating habits, movement and endurance, and a decline in
cognitive function. The purpose of the study was the prevalence of frailty
syndrome in subjects aged 65 years who were hospitalized in an intensive care
unit (ICU) in Greece. Methods: This is a prospective, observational study. The
study sample consisted of families or carers of 36 patients over 65 years of age.
The study was conducted in a General Hospital in Greece, over a period of 1 year.
The Clinical Frailty Scale (CFS) and the 5 criterions frailty phenotype were
used. In addition, the severity of the patients with the APACHE II, SAPS II and
SOFA scales was assessed. For the analysis of the data, the SPSS 19 for windows
statistical package was used and more specifically descriptive statistics and
correlations with parametric methods were performed. Results: Thirty-six severely
ill patients aged 65 years and over (22 women, 14 men) were studied. 25% of the
patients had a positive frailty phenotype, 44% were at an early stage, while
30.6% had a frailty negative phenotype. A significant correlation between CFS and
APACHE (P=0.041), age (P=0.033), sex (P=0.049) and ADL mobility index (P=0.001)
was found to be significant. Concerning mortality, 36.1% of patients died in ICU,
11.1% died within the next 6 months and 38.9% were alive. Conclusions: The
findings of the study highlighted the onset of frailty syndrome in ICU patients.
The objective assessment of the frailty syndrome of the seriously ill patient as
well as the prognostic markers provides a clearer picture of its out-of-hospital
condition and contributes to the collection of information on the outcomes of the
in-hospital treatment.
PMID- 29955572
TI - Trends in total ankle arthroplasty and revisions in the Medicare database.
AB - Background: High failure rates and unacceptable patient outcomes have kept total
ankle arthroplasty (TAA) from becoming a favorable treatment option. Modern
prosthetic designs and techniques have improved outcomes and decreased revision
rates. Current literature has not adequately investigated the recent trends in
TAA utilization and revision rate. The purpose of this study was to determine the
trends in TAA utilization and the rate of revision TAA by analyzing a
comprehensive Medicare database for procedures performed between 2005 and 2012.
Methods: A retrospective review of a comprehensive Medicare database within the
PearlDiver Supercomputer application (Warsaw, IN) of the index procedures TAA and
revision TAA was conducted. Patients who underwent TAA and revision TAA were
identified by Current Procedural Terminology (CPT)-27702, 27703, and
International Classification of Disease ninth revision (ICD) codes 81.56, 81.59
respectively. The primary outcomes of this study were annual revision incidence
and TAA annual utilization. Demographic data such as age, gender, and
geographical location of patients were also examined. Results: Within our study
period of 2005-2012 there was a reported total of 7,181 TAAs and 1,431 revision
TAAs which is a revision incidence of 19.928% amongst the Medicare population.
The compound annual growth rate (CAGR) was 16.37% for TAA, 7.74% for revision
TAA, and a mean 7.41% annual revision incidence. Amongst females there were 3,568
TAA and 731 revision TAA compared with 3,336 TAA and 613 revision TAA amongst
males. The greatest amount of TAA and revision TAA were found in the 65-69 age
group followed by the 70-74 age group. Regionally, the highest number of TAA and
revision TAA were found in the South and the lowest in the Northeast.
Conclusions: Our analysis of the Medicare database shows that there is a high
rate of annual growth in TAA utilization (16.37%) and revision TAA (7.74%)
indicating that there is an increased demand for TAA in the Unites States.
However, failed TAA can have serious consequence and revision TAA remains to have
suboptimal results. This study highlights the recent trends in ankle arthroplasty
and serves to increase awareness of this increasingly popular procedure.
PMID- 29955573
TI - Total knee replacement modifies the preoperative tibial torsion angle-similar
results between computer-assisted and standard technique.
AB - Background: Malpositioning of the components in total knee replacement (TKR) can
result in failure or deficient outcomes of the surgical procedure. In the tibial
segment, the rotational position of the tray should reproduce the mechanical axis
without modifying physiological tibial torsion. Methods: A randomised,
prospective study was made of 74 patients subjected TKR involving the standard
technique (38 cases) and navigation surgery (36 cases). A computed tomography
study of the knee and ankle was made before the operation and after arthroplasty
implantation, in order to identify the position of the prosthetic tibial tray in
the transverse axis and the tibial torsion angle. Results: The rotation of the
tibial tray changed from its preoperative to postoperative range, but no
significant differences were found between the navigated and the standard groups.
The presence of preoperative deformities in the frontal plane did not modify the
changes in the rotation of the tibial component. The mean preoperative tibial
torsion angle was 17.76o (SD =10.15) of external rotation, with no significant
differences in relation to the previous frontal deformity. After TKR, the tibial
torsion angle was 15.36o (SD =7.16) (P=0.021). There were no differences in final
tibial torsion between the knees operated upon with the standard instruments and
those subjected to computer-assisted surgery (CAS; P=0.157). Conclusions: TKR
surgery modifies preoperative tibial torsion. Neither mechanical instrumentation
nor navigation surgery precisely reproduces the rotational axis of the leg.
PMID- 29955574
TI - Impact factors of orthopaedic journals between 2010 and 2016: trends and
comparisons with other surgical specialties.
AB - Background: With increased legislative efforts to utilize evidence-based medicine
as a guide for clinical practice, orthopaedists feel increasing pressure to
publish research in higher-quality journals that reach a larger audience. Impact
factor (IF) is used to quantify and rank journal apparent quality, and is the
most standardized method for journal appraisal. In this study, we assessed the
trends for IF among orthopaedic journals and compared these trends to those of
medicine and general surgery journals. Methods: Journal IFs from Journal Citation
Reports (JCR) between the years 2010 to 2016 were obtained and analyzed for
trends. Only journals that were considered primarily orthopaedic journals were
included. The top 10 journals by IF in both internal medicine and surgery were
also included for comparison. Each journal was analyzed by IF, and trends across
time were noted. The differences in mean IF between orthopaedic specialty groups
were analyzed using an independent samples t-test. Results: The mean IF of
orthopaedic increased from 1.4 (range, 0.0-3.9) in 2010 to 1.9 (range, 0.5-5.7)
in 2016. In 2016, the percentage of English journals increased to 87.3% (n=48),
while the percentage of journals published in the United States was 47.3% (n=26).
There was a significant difference between the IF of journals published in
English and those published in other languages (P=0.004). The mean IF of both
general and specialized orthopaedic journals increased from 2010 to 2016, but the
difference was nonsignificant. The mean IF of the top 10 journals in both surgery
and internal medicine also increased from 2010 to 2016, but the increase was also
nonsignificant. Conclusions: Overall, the mean IF for peer-reviewed orthopaedic
journals has increased in the past years, as has the number of journals. English
journals from the United States continue to have the largest impact when compared
to non-English journals and journals from outside the United States. Future
studies should aim to better qualify journal impact, while limiting confounders
such as self-citation.
PMID- 29955575
TI - No association between systemic complement activation and intensive care unit
acquired weakness.
AB - Background: The main risk factors for intensive care unit-acquired weakness (ICU
AW) are sepsis, the systemic inflammatory response syndrome (SIRS) and multiple
organ dysfunction. These risk factors are associated with systemic complement
activation. We hypothesized that critically ill patients who develop ICU-AW have
increased systemic complement activation compared to critically ill patients who
do not develop ICU-AW. Methods: Complement activation products C3b/c, C4b/c and
C5a were measured in plasma of ICU patients with mechanical ventilation for >=48
hours. Samples were collected at admission to the ICU and for 6 consecutive days.
ICU-AW was defined by a mean Medical Research Council (MRC) score <4. We compared
the level of complement activation products between patients who did and who did
not develop ICU-AW. Results: Muscle strength measurements and complement assays
were available in 27 ICU patients, of whom 13 patients developed ICU-AW.
Increased levels of C4b/c were seen in all patients. Neither admission levels,
nor maximum, minimum and mean levels of complement activation products were
different between patients who did and did not develop ICU-AW. Conclusions:
Complement activation is seen in critically ill patients, but is not different
between patients who did and who did not develop ICU-AW.
PMID- 29955576
TI - Atherosclerosis as autoimmune disease.
AB - No attention is usually focused on the possible involvement of immune mechanisms,
particularly of autoimmunity, on the development and progress of atherosclerosis.
The pioneering work occurring almost 50 years ago was overlooked, and the idea of
atherosclerosis as an autoimmune disease only started gaining traction about 10
years ago. Our review discusses the recent findings and offers insights into the
possibility that alterations of the immune system play a significant role in the
development of atherosclerosis.
PMID- 29955577
TI - Esophagectomy with gastric conduit reconstruction for benign disease: extreme but
important.
AB - Esophagectomy is usually performed to resect esophageal cancer. However, there
are numerous other indications for esophagectomy, including Barrett's esophagus
with high-grade dysplasia (HGD) and some benign diseases such as obstruction, end
stage achalasia, esophagus perforation or disruption, benign neoplasm, and severe
caustic injury. For these patients, esophagectomy could relieve their symptom
obviously. However, esophagectomy causes huge trauma, induces quite high
morbidity and mortality, and may decreases patients' quality of life obviously
due to postoperative reflux, dumping, anastomotic stricture and other
complications. Accordingly, the considerations of a surgery must be carefully
deliberated, including the underlying disorder, lesions localization, extent of
disease, and options for esophageal replacement. For patients received
esophagectomy and alimentary tract reconstruction, gastric conduit is the most
common used replacement organ, then colon and jejunum. This review demonstrated
the importance and technical experience of esophagectomy with gastric conduit
reconstruction for benign diseases.
PMID- 29955578
TI - Teeth infection may "shunt" through Fontan in high-altitude conditions.
AB - The Fontan surgery involves the creation a conduit between the inferior vena cava
and the right pulmonary artery. This conduit has a small fenestration that shunts
the blood from right to left in case the pulmonary blood flow is limited; namely,
if the pulmonary vascular resistance (PVR) is increased then the shunt is
increased. Bacteria may bypass the pulmonary circulation and easily get access to
the systemic circulation (bacteremia). We report the case of a patient that
underwent Fontan surgery in 2010 and remained in a high-altitude city for 7
years, during this time he was asymptomatic until 2017 when he developed a brain
abscess due to Streptococcus gordonii, a pathogen of dental plaque. Since high
altitude may raise PVR in response to reduction in the partial pressure of
oxygen, we conclude that the long-term outcome of increased altitude on Fontan
hemodynamics can lead to the shunt of teeth flora and consequently leading to
severe infections.
PMID- 29955579
TI - Exploring heterogeneity in clinical trials with latent class analysis.
AB - Case-mix is common in clinical trials and treatment effect can vary across
different subgroups. Conventionally, a subgroup analysis is performed by dividing
the overall study population by one or two grouping variables. It is usually
impossible to explore complex high-order intersections among confounding
variables. Latent class analysis (LCA) provides a framework to identify latent
classes by observed manifest variables. Distal clinical outcomes and treatment
effect can be different across these classes. This paper provides a step-by-step
tutorial on how to perform LCA with R. A simulated dataset is generated to
illustrate the process. In the example, the classify-analyze approach is employed
to explore the differential treatment effects on distal outcomes across latent
classes.
PMID- 29955580
TI - Estimate risk difference and number needed to treat in survival analysis.
AB - The hazard ratio (HR) is a measure of instantaneous relative risk of an increase
in one unit of the covariate of interest, which is widely reported in clinical
researches involving time-to-event data. However, the measure fails to capture
absolute risk reduction. Other measures such as number needed to treat (NNT) and
risk difference (RD) provide another perspective on the effectiveness of an
intervention, and can facilitate clinical decision making. The article aims to
provide a step-by-step tutorial on how to compute RD and NNT in survival analysis
with R. For simplicity, only one measure (RD or NNT) needs to be illustrated,
because the other measure is a reverse of the illustrated one (NNT=1/RD). An
artificial dataset is composed by using the survsim package. RD and NNT are
estimated with Austin method after fitting a Cox-proportional hazard regression
model. The confidence intervals can be estimated using bootstrap method.
Alternatively, if the standard errors (SEs) of the survival probabilities of the
treated and control group are given, confidence intervals can be estimated using
algebraic calculations. The pseudo-value model provides another method to
estimate RD and NNT. Details of R code and its output are shown and explained in
the main text.
PMID- 29955581
TI - Time-varying covariates and coefficients in Cox regression models.
AB - Time-varying covariance occurs when a covariate changes over time during the
follow-up period. Such variable can be analyzed with the Cox regression model to
estimate its effect on survival time. For this it is essential to organize the
data in a counting process style. In situations when the proportional hazards
assumption of the Cox regression model does not hold, we say that the effect of
the covariate is time-varying. The proportional hazards assumption can be tested
by examining the residuals of the model. The rejection of the null hypothesis
induces the use of time varying coefficient to describe the data. The time
varying coefficient can be described with a step function or a parametric time
function. This article aims to illustrate how to carry out statistical analyses
in the presence of time-varying covariates or coefficients with R.
PMID- 29955582
TI - Subgroup identification in clinical trials: an overview of available methods and
their implementations with R.
AB - Randomized controlled trials (RCTs) usually enroll heterogeneous study
population, and thus it is interesting to identify subgroups of patients for whom
the treatment may be beneficial or harmful. A variety of methods have been
developed to do such kind of post hoc analyses. Conventional generalized linear
model is able to include prognostic variables as a main effect and predictive
variables in an interaction with treatment variable. A statistically significant
and large interaction effect usually indicates potential subgroups that may have
different responses to the treatment. However, the conventional regression method
requires to specify the interaction term, which requires knowledge of predictive
variables or becomes infeasible when there is a large number of feature
variables. The Least Absolute Shrinkage and Selection Operator (LASSO) method
does variable selection by shrinking less clear effects (including interaction
effects) to zero and in this way selects only certain variables and interactions
for the model. There are many tree-based methods for subgroup identification. For
example, model-based recursive partitioning incorporates parametric models such
as generalized linear models into trees. The model incorporated is usually a
simple model with only the treatment as covariate. Predictive and prognostic
variables are found and incorporated automatically via the tree. The present
article gives an overview of these methods and explains how to perform them using
the free software environment for statistical computing R (version 3.3.2). A
simulated dataset is employed for illustrating the performance of these methods.
PMID- 29955583
TI - Antihypertensive drug therapy.
PMID- 29955584
TI - Can pancreatitis be treated by inhibiting Ca2+ signaling?
PMID- 29955585
TI - To repair or to replace: four decades in the making.
PMID- 29955586
TI - Increasing diagnostic yield by RNA-Sequencing in rare disease-bypass hurdles of
interpreting intronic or splice-altering variants.
PMID- 29955587
TI - Inconclusive evidence to support the use of minimally-invasive radiofrequency
denervation against chronic low back pain.
PMID- 29955588
TI - Improving CT screening for lung cancer with a highly predictive risk model.
PMID- 29955589
TI - SUSTAINable management of type 2 diabetes: feasibility of use and safety of
semaglutide.
PMID- 29955590
TI - Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with evolocumab:
powerful low-density lipoprotein cholesterol (LDL-C) lowering and improved
cardiovascular outcomes without an increase in the risk of diabetes mellitus.
PMID- 29955591
TI - Incretin-based therapy and pancreatitis: accumulating evidence and unresolved
questions.
PMID- 29955592
TI - Puzzle over active surveillance for micropapillary thyroid carcinoma.
AB - It is worth distinguishing between the two strategies of management for low risk
micropapillary thyroid cancer (MPTC). Immediate therapy, whereas active
surveillance (AS) entails delivering curative treatment on signs of disease
progression. AS appears to reduce overtreatment in patients with low-risk MPTC
without compromising cancer-specific survival at 10 years. Therefore, AS is an
option for select patients who want to avoid the side-effects inherent to the
different types of immediate treatment. However, inclusion criteria for AS and
the most appropriate method of monitoring patients on AS have not yet been
standardized.
PMID- 29955593
TI - A critical electrocardiographic pattern in the age of cardiac biomarkers.
PMID- 29955594
TI - Histological examination of post-mortem brains of children with nodding syndrome.
PMID- 29955596
TI - Incorrect cell line validation and verification.
PMID- 29955595
TI - Primary melanoma of the testis: myth.
PMID- 29955597
TI - Extending Shelf Life of Indonesian Soft Milk Cheese (Dangke) by Lactoperoxidase
System and Lysozyme.
AB - Dangke, a type of fresh soft cheese made of bovine and buffalo milk, is a
traditional dairy product used in South Sulawesi, Indonesia. It is prepared from
fresh milk using the conventional method, which easily destroys the quality. This
study was conducted to assess whether using lactoperoxidase system and lysozyme
as preservative agents could suppress the growth of bacteria in dangke. The pH
value, total microbial count, and hardness of dangke were determined to measure
the quality. Lactoperoxidase and lysozyme were purified from fresh bovine milk,
and their purity was confirmed using SDS-PAGE. The combination of lactoperoxidase
system and lysozyme was able to remarkably suppress the total microbial count in
dangke from 7.78 +/- 0.67 to 5.30 +/- 0.42 log CFU/ml during 8 h of storage at
room temperature. Preserving dangke in this enzyme combination affected its
hardness, but there was no remarkable change in the pH value. Results of this
study may provide knowledge to utilize a new method to preserve the quality of
dangke.
PMID- 29955598
TI - Biological Effects and Biodistribution of Bufotenine on Mice.
AB - Bufotenine is an alkaloid derived from serotonin, structurally similar to LSD and
psilocin. This molecule is able to inhibit the rabies virus infection in in vitro
and in vivo models, increasing the survival rate of infected animals. Being a
very promising molecule for an incurable disease and because of the fact that
there is no consensus regarding its neurological effects, this study aimed to
evaluate chronic treatment of bufotenine on behavior, pathophysiology, and
pharmacokinetics of mice. Animals were daily treated for 21 consecutive days with
0.63, 1.05, and 2.1 mg/animal/day bufotenine and evaluated by open field test and
physiological parameters during all the experiment. After this period, organs
were collected for histopathological and biodistribution analysis. Animals
treated with bufotenine had mild behavioral alterations compared to the control
group, being dose-response relationship. On the other hand, animals showed normal
physiological functions and no histological alterations in the organs. With high
doses, an inflammatory reaction was observed in the site of injection, but with
no cellular damage. The alkaloid could be found in the heart and kidney with all
doses and in the lungs and brain with higher doses. These results show that the
effective dose, 0.63 mg/day, is safe to be administered in mice, since it did not
cause significant effects on the animals' physiology and on the CNS. Higher doses
were well tolerated, causing only mild behavioral effects. Thus, bufotenine might
be a drug prototype for rabies treatment, an incurable disease.
PMID- 29955599
TI - Using a Somatosensory Controller to Assess Body Size for Size-Specific Dose
Estimates in Computed Tomography.
AB - Computed tomography (CT) has been widely used in the healthcare environment.
Presently, the radiation dose in CT is determined using the size-specific dose
estimate (SSDE). Accurate assessment of individual's body size is essential for
dose estimation. In this study, we integrated a somatosensory controller with a
CT scanner to measure patient's anterior-posterior diameter (APD) and lateral
diameter (LATD) and calculate the corresponding effective diameter (ED). A total
of 108 individuals with an average age of 38.6 years were enrolled in this study.
Microsoft Kinect was used to acquire the depth image of subjects. A grayscale-to
surface height conversion curve was created using acrylic sheets for APD
estimation. The APD, LATD, and ED were measured and compared with the results
obtained using F ruler and CT images. The mean absolute differences for APD,
LATD, and ED between Kinect and F ruler measurements were 5.2%, 1.3%, and 2.5%,
respectively, while those between Kinect and CT measurements were 8.8%, 2.6%, and
5.0%, respectively. Kinect can replace CT or F ruler for real-time body size
measurements. The use of the somatosensory controller has the advantages of
simple, low cost, no radiation, and automatic calculation. It can accurately
estimate patient's APD, LATD, and ED for SSDE.
PMID- 29955600
TI - URG11 Regulates Prostate Cancer Cell Proliferation, Migration, and Invasion.
AB - Upregulated gene 11 (URG11), a new gene upregulated by hepatitis B virus X
protein, is involved in the development and progression of several tumors,
including liver, stomach, lung, and colon cancers. However, the role of URG11 in
prostate cancer remains yet to be elucidated. By determined expression in human
prostate cancer tissues, URG11 was found significantly upregulated and positively
correlated with the severity of prostate cancer, compared with that in benign
prostatic hyperplasia tissues. Further, the mRNA and protein levels of URG11 were
significantly upregulated in human prostate cancer cell lines (DU145, PC3, and
LNCaP), compared with human prostate epithelial cell line (RWPE-1). Moreover, by
the application of siRNA against URG11, the proliferation, migration, and
invasion of prostate cancer cells were markedly inhibited. Genetic knockdown of
URG11 also induced cell cycle arrest at G1/S phase, induced apoptosis, and
decreased the expression level of beta-catenin in prostate cancer cells.
Overexpression of URG11 promoted the expression of beta-catenin, the growth, the
migration, and invasion ability of prostate cancer cells. Taken together, this
study reveals that URG11 is critical for the proliferation, migration, and
invasion in prostate cancer cells, providing the evidence of URG11 to be a novel
potential therapeutic target of prostate cancer.
PMID- 29955601
TI - Adaptation and Validation of the Malay Version of the Osteoarthritis Knee and Hip
Quality of Life Questionnaire among Knee Osteoarthritis Patients.
AB - Objective: To adapt and validate the Malay version of Osteoarthritis Knee and Hip
Quality of Life (OAKHQOL) questionnaire. Design: The OAKHQOL was adapted into
Malay version using forward-backward translation methodology. It was then
validated in a cross-sectional study of 191 patients with knee osteoarthritis
(OA). Patients completed the OAKHQOL and Western Ontario and McMaster
Universities Osteoarthritis Index (WOMAC) questionnaire. Confirmatory analysis,
reliability analysis, and Pearson correlation test were performed. Results: The
new five-factor model of 28 items demonstrated an acceptable level of goodness of
fit (comparative fit index = 0.915, Tucker-Lewis index = 0.905, incremental fit
index = 0.916, chi-squared/degree of freedom = 1.953, and root mean square error
of approximation = 0.071), signifying a fit model. The Cronbach's alpha value and
the composite reliability of each construct ranged from 0.865 to 0.933 and 0.819
to 0.921, respectively. The Pearson correlation coefficient between the OAKHQOL
and the WOMAC showed adequate criterion validity. Known groups validity showed
statistical difference in body mass index in physical activity, mental health,
and pain construct. The pain domain was statistically different between the age
groups. Conclusion: The Malay version OAKHQOL questionnaire is a valid and
reliable instrument to assess health-related quality of life in knee OA patients.
PMID- 29955602
TI - Major Maternal Dietary Patterns during Early Pregnancy and Their Association with
Neonatal Anthropometric Measurement.
AB - Background: Anthropometric measurements of newborn infant are widely assessed as
determinants of maternal nutrition. Although earlier studies have mostly examined
the effects of particular nutrients or foods during gestational period on
neonatal anthropometric measurements, there are few studies regarding the
association of dietary patterns and mentioned measurements. So, the purpose of
the current study was to investigate the association between major maternal
dietary patterns and neonatal anthropometric measurements including body weight,
head circumference, and height. Methods: The current prospective observational
study is based on the data collected from 812 pregnant women. Dietary data was
collected using a validated semiquantitative food frequency questionnaire.
Results: Three identified major dietary patterns according to the results
obtained from the factor loading matrix were (i) "western dietary pattern"; (ii)
"traditional dietary pattern"; (iii) "healthy dietary pattern". Overall, this
study demonstrated a positive significant association between high adherences to
western dietary pattern and chance of having low birth weight infant. However,
such associations were not seen in women taking healthy and traditional dietary
patterns. Conclusion: We found that healthier maternal dietary patterns during
early pregnancy might be associated with lower risk of low birth weight. Further
studies are required to confirm these findings.
PMID- 29955603
TI - The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the
Chronic Heart Failure Risk in the Chinese.
AB - Aim: To investigate the genetic contribution of adenosine A3 receptor (ADORA3)
gene polymorphisms in the pathogenesis of chronic heart failure (CHF). Methods:
Firstly, a case-control study was performed to investigate the association of
ADORA3 polymorphisms with CHF risk. Three hundred northern Chinese Han CHF
patients and 400 ethnicity-matched healthy controls were included. Four
polymorphisms were genotyped. This case-control study was also replicated in 304
CHF patients and 402 controls from southern China. Finally, the functional
variability of positive polymorphism was analyzed using luciferase reporter assay
and real-time PCR. Results: Overall, the rs1544223 was significantly associated
with CHF risk under the dominant model (P = 0.046, OR = 1.662, 95% CI = 1.009
2.738). But it did not affect disease severity. These results were also
consistent in replicated population. In addition, the transcriptional activity
for promoter with the A allele was lower than that with the G allele (n = 3,
4.501 +/- 0.308 versus 0.571 +/- 0.114, P < 0.01) and ADORA3 mRNA levels were
significantly higher in GG homozygotes than subjects carrying GA (n = 6, 0.058 +/
0.01 versus 0.143 +/- 0.068, P = 0.004) or AA genotypes (n = 6, 0.065 +/- 0.01
versus 0.143 +/- 0.068, P = 0.008). Conclusions: Should the findings be validated
by further studies with larger patient samples and in different ethnicities, they
may provide novel insight into the pathogenesis of CHF.
PMID- 29955605
TI - Implementation Process and Impacts of a Participatory HIV Research Project with
Key Populations.
AB - A participatory HIV research project was conducted with sex workers (SW) and men
who have sex with men (MSM) to understand epidemiological HIV dynamics and
associated sociobehavioural factors among these vulnerable groups. We examine the
impact of this project, critically analysing the processes undertaken and
focusing on the advantages and the challenges faced. A partnership was built
through two Community Advisory Boards (CABs) and a Scientific Commission (SC).
Regular meetings, workshops, and focus groups were conducted with CABs, SC, and
partners to assess the processes and outcomes of the project implementation. This
participatory research produced change processes with impacts at different
levels: individuals, community organizations, health professionals, academics,
and policy-makers. Advantages of the participatory process were encountered but
also challenges, evidencing the dynamic and complex nature of each project's
stage. This project showed that participatory research can work as an
intervention. Indeed, it triggered a dynamic and interactive process of knowledge
coproduction and translation into effective community-oriented health actions and
policies. The participatory research reproduced an innovative alliance for HIV
prevention and sexual health promotion responsive to local needs and priorities.
Further efforts are needed to systematize and evaluate the processes and impacts
of participatory health research.
PMID- 29955606
TI - The Detection and Phylogenetic Analysis of Bovine Hepacivirus in China.
AB - Hepacivirus has been identified in cattle in Africa, Europe, and South America.
In this survey of bovine hepacivirus (BovHepV) in 131 serum samples from Chinese
cattle herds using RT-PCR, five of 131 sera were BovHepV positive, with the
infection rate of 3.82%. Phylogenetic analysis based on the partial NS3 coding
sequence showed that the BovHepV of the five positive samples clustered with
other BovHepV but formed a separate branch. The results indicated that these new
BovHepV represent emerging and novel strains. Further investigations are
necessary to determine the epidemiology and viral pathogenesis of these BovHepV
strains, as well as the potential threat to ruminant and livestock workers in
China.
PMID- 29955604
TI - Modeling Renal Disease "On the Fly".
AB - Detoxification is a fundamental function for all living organisms that need to
excrete catabolites and toxins to maintain homeostasis. Kidneys are major organs
of detoxification that maintain water and electrolyte balance to preserve
physiological functions of vertebrates. In insects, the renal function is carried
out by Malpighian tubules and nephrocytes. Due to differences in their
circulation, the renal systems of mammalians and insects differ in their
functional modalities, yet carry out similar biochemical and physiological
functions and share extensive genetic and molecular similarities. Evolutionary
conservation can be leveraged to model specific aspects of the complex mammalian
kidney function in the genetic powerhouse Drosophila melanogaster to study how
genes interact in diseased states. Here, we compare the human and Drosophila
renal systems and present selected fly disease models.
PMID- 29955607
TI - High Vimentin Expression Predicts a Poor Prognosis and Progression in Colorectal
Cancer: A Study with Meta-Analysis and TCGA Database.
AB - The aim of this study was to evaluate the role of vimentin expression in the
prognosis and progression of CRC. Meta-analysis was conducted to investigate the
correlations between vimentin and prognosis and clinicopathological features in
CRC. Literatures were searched by PubMed, Embase, ClinicalKey, CNKI, VIP, and
WanFang databases. The Cancer Genome Atlas (TCGA) database was used to assess the
association of vimentin expression with survival rate in CRC. Eleven reports with
1969 cases were included in the meta-analysis. The results showed that positive
vimentin expression predicted a poor overall survival (OS) in the univariate
analysis (HR: 2.087, 95%CI: 1.660-2.625) and multivariate analysis (HR: 1.633,
95%CI: 1.223-2.181). Vimentin overexpression also conferred worse disease-free
survival (DFS) in the univariate analysis (HR: 2.069, 95%CI: 1.024-4.179) and
multivariate analysis (HR: 2.802, 95%CI: 1.421-5.527). Moreover, upregulated
vimentin is related to lymph node metastasis (OR: 2.288, 95%CI: 1.159-4.517), TNM
stages (OR: 1.957, 95%CI: 1.333-2.873), and N stage (OR: 2.316, 95%CI: 1.482
3.620). Analysis of TCGA database indicated that elevated vimentin predicated a
shorter OS (p=0.033). Our findings reveal that upregulated vimentin contributes
to the progression and poor prognosis of CRC. Vimentin may be a prognostic
biomarker and therapeutic target in patients with CRC.
PMID- 29955608
TI - Clinical Relevance of Bone Density Values from CT Related to Dental Implant
Stability: A Retrospective Study.
AB - Purpose: The majority of the techniques used to assess the primary implant
stability are subjective and empirical and can be used during or after the
surgery. The aim of this study is to evaluate the bone density prior to surgery,
in order to give recommendations to the clinician about the best surgical
technique and the type of implant which is needed. Materials and Methods: A
surgeon operated on 75 patients for 269 implants over the period 2010-2014. He
required a CT to plan the surgery and he documented the type, the diameters, and
the lengths of the implants, the insertion torque, and the ISQ values. At a later
stage another clinician measured bone density and cortical thickness. We
endeavoured to get the most accurate superimposition between the implants placed
by the surgeon and those placed by the clinician. Results: In maxilla ISQ showed
a significant positive correlation with HU values detected for coronal-buccal (r
= 0.302; p = 0.020) and middle-lingual (r = 0.295; p = 0.023). Torque showed a
positive correlation with cortical bone thickness at the middle of the ridge (rho
= 0.196; p = 0.032). Conclusion: It is important to take into consideration the
Hounsfield Units and the cortical thickness as predictive parameters during the
preoperative assessment, with regard to the choice of the implant type as well as
the surgical technique.
PMID- 29955609
TI - Prenatal Diagnosis and Genetic Analysis of a Fetus with Joubert Syndrome.
AB - Objective: To diagnose and explore the genetic cause of Joubert syndrome (JS) in
a fetus. Methods: Prenatal ultrasound and magnetic resonance imaging (MRI)
examinations were performed, and genetic analysis was conducted using targeted
next-generation sequencing (NGS) and Sanger sequencing. Results: Prenatal
ultrasound and MRI examinations showed cerebellar vermis hypoplasia and molar
tooth sign (MTS); hence the fetus was diagnosed with JS. Further genetic analysis
revealed a known missense variant (c.3599C>T, p.A1200V) and a novel missense
variant (c.3857G>A, p.R1286H) in the C5orf42 gene of the fetus. Conclusion: Our
study provides insights into prenatal and early diagnosis of JS and expands the
variation spectrum of C5orf42 gene.
PMID- 29955610
TI - Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma.
AB - The aim of the present study was to determine if the Ki-67 labelling index
reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration
in blood serum of pituitary adenoma patients. The study was conducted in the
Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were
analysed based on magnetic resonance imaging findings. The suprasellar extension
and sphenoid sinus invasion by pituitary adenoma were classified according to
Hardy classification modified by Wilson. Knosp classification system was used to
quantify the invasion of the cavernous sinus. The Ki-67 labelling index was
obtained by immunohistochemical analysis with the monoclonal antibody, and serum
levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA).
Sixty-nine PA tissue samples were investigated. Serum levels of IL-17A were
determined in 60 patients with PA and 64 control subjects. Analysis revealed
statistically significantly higher Ki-67 labelling index in invasive compared to
noninvasive pituitary adenomas. Median serum IL-17A level was higher in the
pituitary adenoma patients than in the control group. Conclusion. IL-17A might be
a significant marker for patients with pituitary adenoma and Ki-67 labelling
index in case of invasive pituitary adenomas.
PMID- 29955612
TI - Chemokine C-C Motif Ligand 4 Gene Polymorphisms Associated with Susceptibility to
Rheumatoid Arthritis.
AB - Chemokine C-C motif ligand 4 (CCL4) gene is a chemokine-encoding gene, and the
polymorphism of CCL4 gene has been shown to predict risk of various diseases. We
want to investigate whether the single nucleotide polymorphisms (SNPs) of the
CCL4 gene can predict the risk of rheumatoid arthritis (RA). Between 2007 and
2015, we recruited 217 patients diagnosed with RA and 371 control participants.
Comparative genotyping of the rs1634507, rs10491121, and rs1719153 SNPs was
performed. When compared with participants with the A/A genotype of rs1719153,
those with the A/T genotype were less likely to develop RA, as were those with
the A/T+T/T genotype. The protective effect of the T-containing genotype was even
more prominent among females. Those with A/T in rs1719153 were 56% less likely to
develop RA compared with females with A/A; a similar protective effect was seen
for females with the A/T+T/T genotype compared with those with A/A. The GTEx
database revealed that patients carrying the T/T genotype had lower levels of
CCL4 gene expression than those carrying the A/A genotype. These results indicate
that the nucleotide T over the rs1719153 is associated with decreased CCL4 gene
expression and decreased risk for RA.
PMID- 29955611
TI - Prognosis and Histological Classification in Elderly Patients with ANCA
Glomerulonephritis: A Registry-Based Cohort Study.
AB - Background: The value of a histologic classification scheme to classify patients
with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN)
into focal, mixed, crescentic, and sclerotic types for predicting risk of end
stage renal disease (ESRD) is well documented. However, the prognostic value of
histological classification specifically in elderly patients (>=70 years) with
ANCA-GN has not previously been investigated. Methods: Patients with biopsy
verified pauci-immune necrotizing glomerulonephritis were identified from the
Norwegian Kidney Biopsy Registry between 1991 and 2012 and those >=70 years of
age at the time of diagnosis and having positive anti-neutrophil cytoplasmic
antibody serology were included in this study. The incidence rate of ESRD and/or
death was determined by linking the study cohort to the Norwegian Renal Registry
and the Population Registry of Norway. The ESRD-free survival and patient
survival were compared between the 4 histological types. Results: Of the 81
patients included, 20 progressed to ESRD and 34 died. The 1-year and 5-year ESRD
free survival varied between histological groups (p = 0.003) as follows: focal,
97% and 97%, respectively; mixed, 70% and 57%; crescentic, 76% and 63%; and
sclerotic, 49% and 49%. Patient survival did not differ significantly between
groups (p = 0.30). Conclusion: Histological classification in elderly patients
with ANCA-GN is useful for predicting ESRD but not survival.
PMID- 29955613
TI - Exogenous Tissue Inhibitor of Metalloproteinase-2 Affects Matrix
Metalloproteinase-2 Expression in Conjunctival Filtering Blebs and Bleb Scarring
in Rats.
AB - Objective: To examine the effect of tissue inhibitor of metalloproteinase-2 (TIMP
2) on conjunctival filtering bleb scarring. Methods: A model of conjunctival
filtering bleb was established whereby rats were injected with saline, blank
adenoviral vector, or adenoviral vector carrying TIMP-2 into the bleb. Filtration
bleb formation and matrix metalloproteinase-2 (MMP-2) expression were examined.
Results: All operated eyes formed obvious elevated blebs on day 1. In the normal
saline group, empty plasmid group, and gene transfection group maintenance time
of filtrating blebs was 5-14, 5-14, and 6-16 days, and average survival time was
8.24, 8.16, and 9.44 days, respectively. MMP-2 expression increased slightly in
the gene transfection group at 3 and 5 days after surgery, reached a peak after
14 days, and then gradually decreased. MMP-2 expression was weakly positive in
the normal conjunctival epithelium, but was hardly detected in the lamina
propria. Seven days after surgery, the epithelium and lamina propria of the
conjunctival filtering bleb exhibited strong positive expression in the empty
plasmid group but only weak expression in the adenovirus group. Conclusion:
Exogenous TIMP-2 interfered with local MMP-2 expression, delaying peak expression
of MMP-2 and slowing the scarring of filtering blebs during wound healing of
subconjunctival tissue.
PMID- 29955614
TI - The Plantaris Muscle Tendon and Its Relationship with the Achilles Tendinopathy.
AB - Purpose: Although the plantaris muscle (PM) is vestigial in humans, it has a
significant clinical role in procedures such as grafting. However, recent reports
suggest its potential involvement in the tendinopathy of the midportion of the
Achilles tendon. The aim of the study is therefore to evaluate morphological
variation of the PM with regard to its potential conflict with the Achilles
tendon. Material and Methods: Classical anatomical dissection was performed on
130 lower limbs (71 right, 59 left) fixed in 10% formalin solution. The
morphology of the PM was assessed regarding the relationship between the course
of the plantaris tendon and the calcaneal tendon. Results: The PM was present in
89.2% of cases. The findings indicate the presence of a new type of PM tendon
insertion in which the tendon is inserted into the tarsal canal flexor
retinaculum, potentially affecting the tendinopathy of the tibialis posterior
muscle. In 26 cases (22.4%), insertion blended with the Achilles tendon (Type
II), which may increase the risk of Achilles tendinopathy. Conclusion: The
anatomical variation of PM tendon morphology may create a potential conflict with
the Achilles tendon and the tibialis posterior tendon, thus increasing the
possibility of tendinopathy.
PMID- 29955615
TI - Markers of Anemia in Children with Type 1 Diabetes.
AB - Aim: The aim of the study was to assess markers of anemia in type 1 diabetes
(T1D) children, compare them to results obtained in the control group, and
estimate their relation to BMI SDS. Methods: 94 (59% ?) T1D children without
other autoimmune disorders, aged 12.5 +/- 4.1 years, T1D duration: 4.2 +/- 3.6
years, HbA1c 7.3 +/- 1.5% (57 +/- 12.6 mmol/mol). Sex- and age-matched controls
(43 children). In all children, anthropometric measurements, the blood count,
iron turnover parameters, and vitamin B12 concentration were taken. Results: T1DM
children had significantly higher red cell distribution width (RDW) (13.6 versus
12.6%; p < 0.001), hepcidin (0.25 versus 0.12 ng/ml; p < 0.001), and vitamin B12
concentrations (459 versus 397 pg/ml; p < 0.01) and lower TIBC (59.09 versus
68.15 MUmol/l; p < 0.001) than in the control group. Logistic regression revealed
that RDW, TIBC (both p < 0.001), and hepcidin (p < 0.05) significantly
differentiated both groups. In T1DM children, BMI SDS negatively correlated with
vitamin B12 (p < 0.01) concentration and mean corpuscular hemoglobin
concentration (p < 0.05) and positively with TIBC (p < 0.01) and HbA1c (p <
0.001). Conclusions: Patients and controls differed especially in terms of RDW
and TIBC. In studied T1DM children, BMI SDS was associated to iron metabolism
parameters and vitamin B12 concentration.
PMID- 29955617
TI - Risk Factors for Viridans Group Streptococcal Bacteremia in Neutropenic and Non
neutropenic Patients: A Single Center Case-Case-Control Study.
AB - Background: Viridans group streptococcal (VGS) bacteremia is common among
neutropenic patients. Although VGS bacteremia occurs in non-neutropenic patients,
risk factors are not well established. We conducted a case-case-control study to
identify risk factors for VGS among neutropenic and non-neutropenic patients.
Methods: Patients with VGS bacteremia between January 2009 and December 2014 in
our 200-bed clinical research hospital were identified using microbiology
records. Neutropenic and non-neutropenic patients at the time of positive culture
were matched 1:1 to controls on the basis of neutrophil count (ANC), ward, and
length of stay. We extracted demographic, laboratory, medication, and other
clinical data from chart reviews. Data were analyzed using McNemar's test,
Wilcoxon signed-rank test, and conditional logistic regression modeling. Results:
Among 101 patients, 63 were neutropenic and 38 non-neutropenic at the time of VGS
bacteremia. In multivariable analysis of neutropenic patients, only lower ANC
predicted VGS bacteremia (odds ratio [OR], 0.16; 95% confidence interval [CI],
0.05-0.59; P = 0.006). Recent use of vancomycin was protective (OR, 0.23; 95% CI,
0.07-0.73; P = 0.013). No clinical factors were associated with VGS in the non
neutropenic cases. Conclusions: Only lower ANC nadir increased the risk for VGS
bacteremia in the neutropenic group, and vancomycin was protective. Other
previously described factors (chemotherapy, radiation, oral conditions) related
to neutropenia were not independently associated with VGS bacteremia. No tested
clinical factors predicted infection in the non-neutropenic group. Our results
suggest that VGS bacteremia should be anticipated when making antimicrobial
choices in profoundly neutropenic patients, and merit further exploration in non
neutropenic patients.
PMID- 29955616
TI - Contractile Protein Expression and Phosphorylation and Contractility of Gastric
Smooth Muscles from Obese Patients and Patients with Obesity and Diabetes.
AB - Ingested food is received, mixed, and ground into chyme by distinct gastric
motility patterns. Diabetes impairs gastric muscle function, but the mechanisms
underlying diabetes-induced gastric muscle dysfunction are unknown. Here, we
compared the expression and phosphorylation of Ca2+ sensitization and contractile
proteins in human gastric muscles from obese nondiabetic and diabetic patients.
We also compared the spontaneous phasic contractions and the contractile
responses evoked by electrical field stimulation of cholinergic motor neurons.
Fundus and antrum muscles were obtained from sleeve gastrectomies and were used
in in vitro myobath contractile studies and for capillary electrophoresis and
immunodetection of gamma-actin, CPI-17, pT38-CPI-17, MYPT1, pT853-MYPT1, pT696
MYPT1, myosin light chain (MYL9), pS19-MYL9, myosin light chain kinase (MYLK),
protein phosphatase-1delta (PP1delta), and Rho-associated kinase (ROCK2). In
diabetic fundus muscles, MYLK, ROCK2, and PP1delta expression was unchanged;
MYPT1 and CPI-17 expression was decreased; and the pT853/MYPT1 and pT38/CPI-17
ratios, but not the pT696/MYPT1 ratio, were increased. Although MYL9 expression
was increased, the pS19/MYL9 ratio was unchanged in diabetic fundus muscles. In
diabetic antrum muscles, MYLK and MYL9 expression was unchanged, but ROCK2, CPI
17, and PP1delta expression was decreased. The pT38/CPI-17 ratio was unchanged,
while the pS19/MYL9, pT853/MYPT1, and pT696/MYPT1 ratios were decreased,
consistent with the reduced ROCK2 expression. The frequencies of spontaneous
phasic contractions from nondiabetic and diabetic gastric fundus and antrum
muscles did not significantly differ from each other, regardless of age, sex, or
diabetic status. The fold increases in the contractions of diabetic fundus and
antrum muscles in response to increased frequencies of electrical field
stimulation were significantly lower compared to nondiabetic fundus and antrum
muscles. The altered contractile responses and the protein expression and
phosphorylation in gastric muscles of obese patients with diabetes illustrate the
importance of understanding how smooth muscle Ca2+ sensitization mechanisms
contribute to gastric motility.
PMID- 29955618
TI - Deaths From Pneumonia-New York City, 1999-2015.
AB - Background: "Pneumonia and influenza" are the third leading cause of death in New
York City. Since 2012, pneumonia and influenza have been the only infectious
diseases listed among the 10 leading causes of death in NYC. Most pneumonia and
influenza deaths in NYC list pneumonia as the underlying cause of death, not
influenza. We therefore analyzed death certificate data for pneumonia in NYC
during 1999-2015. Methods: We calculated annualized pneumonia death rates
(overall and by sociodemographic subgroup) and examined the etiologic agent
listed. Results: There were 41 400 pneumonia deaths during the study period,
corresponding to an annualized age-adjusted death rate of 29.7 per 100 000
population. Approximately 17.5% of pneumonia deaths specified an etiologic agent.
Age-adjusted pneumonia death rate declined over the study period and across each
borough. Males had an annualized age-adjusted pneumonia death rate 1.5 (95%
confidence interval [CI], 1.5-1.5) times that of females. Non-Hispanic blacks had
an annualized age-adjusted pneumonia death rate 1.2 (95% CI, 1.2-1.2) times that
of non-Hispanic whites. The annualized pneumonia death rate increased with age
group above 5-24 years and neighborhood-level poverty. Staten Island had an
annualized age-adjusted pneumonia death rate 1.3 (95% CI, 1.2-1.3) times that of
Manhattan. In the multivariable analysis, pneumonia deaths were more likely to
occur among males, non-Hispanic blacks, persons aged >=65 years, residents of
neighborhoods with higher poverty levels, and in Staten Island. Conclusions:
While the accuracy of death certificates is unknown, investigation is needed to
understand why certain populations are disproportionately recorded as dying from
pneumonia in NYC.
PMID- 29955619
TI - Quantification of Hydrogen Sulfide and Cysteine Excreted by Bacterial Cells.
AB - Bacteria release cysteine to moderate the size of their intracellular pools. They
can also evolve hydrogen sulfide, either through dissimilatory reduction of
oxidized forms of sulfur or through the deliberate or inadvertent degradation of
intracellular cysteine. These processes can have important consequences upon
microbial communities, because excreted cysteine autoxidizes to generate hydrogen
peroxide, and hydrogen sulfide is a potentially toxic species that can block
aerobic respiration by inhibiting cytochrome oxidases. Lead acetate strips can be
used to obtain semiquantitative data of sulfide evolution (Oguri et al., 2012).
Here we describe methods that allow more-quantitative and discriminatory measures
of cysteine and hydrogen sulfide release from bacterial cells. An illustrative
example is provided in which Escherichia coli rapidly evolves both cysteine and
sulfide upon exposure to exogenous cystine (Chonoles Imlay et al., 2015;
Korshunov et al., 2016).
PMID- 29955620
TI - Evaluating Point of Sale Tobacco Marketing Using Behavioral Laboratory Methods.
AB - With passage of the 2009 Family Smoking Prevention and Tobacco Control Act, the
FDA has authority to regulate tobacco advertising. As bans on traditional
advertising venues and promotion of tobacco products have grown, a greater
emphasis has been placed on brand exposure and price promotion in displays of
products at the point-of-sale (POS). POS marketing seeks to influence attitudes
and behavior towards tobacco products using a variety of explicit and implicit
messaging approaches. Behavioral laboratory methods have the potential to provide
the FDA with a strong scientific base for regulatory actions and a model for
testing future manipulations of POS advertisements. We review aspects of POS
marketing that potentially influence smoking behavior, including branding, price
promotions, health claims, the marketing of emerging tobacco products, and
tobacco counter-advertising. We conceptualize how POS marketing potentially
influence individual attention, memory, implicit attitudes, and smoking behavior.
Finally, we describe specific behavioral laboratory methods that can be adapted
to measure the impact of POS marketing on these domains.
PMID- 29955621
TI - Evaluation of bone mineralization in former preterm born children: Phalangeal
quantitative ultrasound cannot replace dual-energy X-ray absorptiometry.
AB - Background: Preterm infants are at risk of impaired bone health in later life.
Dual-energy X-ray absorptiometry-scan (DXA) is the gold standard to determine
bone mineralization. Phalangeal quantitative ultrasound (pQUS) is an alternative
technique that is inexpensive, easy to use and radiation-free. The aim of this
study was to investigate whether both techniques reveal equivalent results.
Materials and methods: Sixty former preterm infants (31 boys; 29 girls) received
a DXA and pQUS at age 9 to 10 years. DXA measured bone mineral content (BMC) and
bone mineral density (BMD) for total body and lumbar spine (L1-4), while pQUS
measured the amplitude dependent speed of sound (AD-SoS) and bone transit time
(BTT) at metacarpals II-IV providing continuous values and Z-scores based on age
and sex. Four statistical methods evaluated the association between both
techniques: Pearson's correlation coefficients, partial correlation coefficients
adjusted for gestational age, height and BMI, Bland-Altman analysis and cross
tabulation. Results: Both techniques showed a statistically significant weak
correlation for continuous values as well as Z-scores (0.291-0.462, p < 0.05).
Boys had significant and relatively high correlations (0.468-0.585, p < 0.05). In
comparison, the correlations for girls were not significant. Correlation
coefficients further decreased while calculating the partial correlations. The
Bland-Altman plots showed poor agreement. Sensitivity ranged from 33% to 92% and
specificity from 16% to 68%. Positive and negative predictive values ranged from
4% to 38% and 82% to 97%, respectively. Conclusions: We found statistically
significant weak correlations and poor agreement between DXA and pQUS
measurements. DXA is not equivalent to pQUS and therefore not replaceable by this
technique in former preterm born children at the age of 9 to 10 years.
PMID- 29955622
TI - Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in
osteoporotic mice via modulating Treg-Th17 cell balance.
AB - Osteoporosis is one of the most important but often neglected bone disease
associated with aging and postmenopausal condition leading to bone loss and
fragility. Probiotics have been associated with various immunomodulatory
properties and have the potential to ameliorate several inflammatory conditions
including osteoporosis. Lactobacillus acidophilus (LA) was selected as probiotic
of choice in our present study due its common availability and established
immunomodulatory properties. In the present study, we report for the first time
that administration of LA in ovariectomized (ovx) mice enhances both trabecular
and cortical bone microarchitecture along with increasing the mineral density and
heterogeneity of bones. This effect of LA administration is due to its
immunomodulatory effect on host immune system. LA thus skews the Treg-Th17 cell
balance by inhibiting osteoclastogenic Th17 cells and promoting anti
osteoclastogenic Treg cells in ovx mice. LA administration also suppressed
expression of osteoclastogenic factors (IL-6, IL-17, TNF-alpha and RANKL) and
increased expression of anti-osteoclastogenic factors (IL-10, IFN-gamma). Taken
together the present study for the first time clearly demonstrates the
therapeutic potential of LA as an osteo-protective agent in enhancing bone health
(via tweaking Treg-Th17 cell balance) in postmenopausal osteoporosis.
PMID- 29955623
TI - Thin bones: Vitamin D and calcium handling after bariatric surgery.
AB - Bariatric surgery has proven to be a valuable treatment option for morbid
obesity. However, these procedures can lead to impaired intestinal absorption of
calcium and vitamin D, thereby challenging calcium homeostasis and possibly
contributing to bone loss leading to an increased fracture risk. Besides calcium
and vitamin D malabsorption, hormonal changes occurring after surgery can also be
the source of observed bone loss. In this review, first, a case report will be
discussed, highlighting the relevance of this topic. Afterwards, changes in bone
density and fracture risk, after the two most performed types of bariatric
surgery, Sleeve Gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB) will be
discussed. In addition, we discuss the putative underlying mechanisms leading to
bone changes based on both preclinical and clinical observations. Nonetheless, it
is clear further research is needed to further elucidate the exact mechanisms of
bone loss following bariatric surgery and subsequently identify potential
treatment options for bone preservation.
PMID- 29955624
TI - Activation of mTORC1 in chondrocytes does not affect proliferation or
differentiation, but causes the resting zone of the growth plate to become
disordered.
AB - There are several pitfalls associated with research based on transgenic mice.
Here, we describe our interpretation and analysis of mTORC1 activation in growth
plate chondrocytes and compare these to a recent publication (Yan et al., Nature
Communications 2016, 7:11151). Both laboratories employed TSC1-floxed mice
crossed with collagen type 2-driven Cre (Col2-Cre), but drew substantially
different conclusions. It was reported that activation of mechanistic target of
rapamycin complex 1 (mTORC1) via Tsc1 ablation promotes the hypertrophy of growth
plate chondrocytes, whereas we observe only disorganization in the resting zone,
with no effect on chondrocyte hypertrophy or proliferation. Here, we present our
data and discuss the differences in comparison to the earlier phenotypic
characterization of TSC1 ablation in cartilage. Importantly, we detect Col2-Cre
activity in non-cartilaginous tissues (including the brain) and discuss it in
relation to other studies reporting non-cartilaginous expression of collagen
alpha(1) II. Altogether, we conclude that mouse phenotypes following genetic
ablation using Col2-Cre should be interpreted with care. We also conclude that
activation of mTORC1 by TSC1 ablation in postnatal chondrocytes with inducible
Col2-Cre (Col2-CreERt) leads to disorganization of the resting zone but causes no
changes in chondrocyte proliferation or differentiation.
PMID- 29955625
TI - The roles of vitamin D and dietary calcium in nutritional rickets.
AB - The etiology and pathogenesis of nutritional rickets are becoming progressively
clearer. Vitamin D deficiency has generally been considered the major or only
player in the pathogenesis of nutritional rickets. However, recent research into
calcium deficiency has now provided clinicians with reasons to investigate and
manage patients with nutritional rickets more appropriately. The important
question when assessing cases of nutritional rickets is: "Is it calcium or
vitamin D deficiency or both that play a major role in the pathogenesis of the
disease?" The case presentation in this review highlights the risk factors,
clinical presentation and pathophysiology of nutritional rickets in a young South
African black child from a semi-urban area in Johannesburg, a city with abundant
sunshine throughout the year.
PMID- 29955626
TI - Decreased osteoprogenitor proliferation precedes attenuation of cancellous bone
formation in ovariectomized rats treated with sclerostin antibody.
AB - Sclerostin antibody (Scl-Ab) stimulates bone formation, which with long-term
treatment, attenuates over time. The cellular and molecular mechanisms
responsible for the attenuation of bone formation are not well understood, but in
aged ovariectomized (OVX) rats, the reduction in vertebral cancellous bone
formation is preceded by a reduction in osteoprogenitor (OP) number and
significant induction of signaling pathways known to suppress mitogenesis and
cell cycle progression in the osteocyte (OCy) (Taylor et al., 2016). To determine
if the reduction in OP number is associated with a decrease in proliferation,
aged OVX rats were administered vehicle or Scl-Ab for 9 or 29 days and implanted
with continuous-delivery 5-bromo-2'-deoxyuridine (BrdU) mini-osmotic pumps 5 days
prior to necropsy. The total number of BrdU-labeled osteoblasts (OB) was
quantified in vertebral cancellous bone to indirectly assess the effects of Scl
Ab treatment on OP proliferation at the time of activation of modeling-based bone
formation at day 9 and at the time of maximal mineralizing surface, initial
decrease in OP number, and transcriptional changes in the OCy at day 29. Compared
with vehicle, Scl-Ab resulted in an increase in the total number of BrdU-positive
OB (+260%) at day 9 that decreased with continued treatment (+50%) at day 29.
These differences in proliferation occurred at time points when the increase in
total OB number was significant and similar in magnitude. These findings suggest
that reduced OP proliferation contributes to the decrease in OP numbers, an
effect that would limit the OB pool and contribute to the attenuation of bone
formation that occurs with long-term Scl-Ab treatment.
PMID- 29955627
TI - Differential time-dependent transcriptional changes in the osteoblast lineage in
cortical bone associated with sclerostin antibody treatment in ovariectomized
rats.
AB - Inhibition of sclerostin with sclerostin antibody (Scl-Ab) results in stimulation
of bone formation on cancellous (Cn), endocortical (Ec), and periosteal (Ps)
surfaces in rodents and non-human primates. With long-term dosing of Scl-Ab, the
increase in bone formation is not sustained, attenuating first on Cn surfaces and
later on Ec and Ps surfaces. In Cn bone, the attenuation in bone formation (self
regulation) is associated with transcriptional changes in the osteocyte (OCy)
that would limit mitogenesis and are sustained with continued dosing. The
expression changes in Cn OCy occur coincident with a decrease in osteoprogenitor
(OP) numbers that may directly or indirectly be a consequence of the
transcriptional changes in the OCy to limit OP proliferation. To characterize the
Scl-Ab-mediated changes in cortical (Ct) bone and compare these changes to Cn
bone, densitometric, histomorphometric, and transcriptional analyses were
performed on femur diaphyses from aged ovariectomized rats. Animals were
administered 50 mg/kg/wk of Scl-Ab or vehicle for up to 6 months (183 days),
followed by a treatment-free period (up to 126 days). Scl-Ab increased Ct mass
and area through day 183, which declined slightly when treatment was
discontinued. Ps and Ec bone formation was sustained through the dosing on both
Ct surfaces, with evidence of a decline in bone formation only at day 183 on the
Ec surface. This is in contrast to Cn bone, where reduced bone formation was
observed after day 29. TaqMan analysis of 60 genes with functional roles in the
bone using mRNA isolated from laser capture micro-dissection samples enriched for
Ec osteoblasts and Ct OCy suggest a pattern of gene expression in Ct bone that
differed from Cn, especially in the OCy, and that corresponded to observed
differences in the timing of phenotypic changes. Notable with Scl-Ab treatment
was a "transcriptional switch" in Ct OCy at day 183, coincident with the initial
decline in bone formation on the endocortex. A consistent sustained increase of
expression for most genes in response to Scl-Ab was observed from day 8 through
day 85 at the times of maximal bone formation on both Ct surfaces; however, at
day 183, this increase was reversed, with expression of these genes generally
returning to control values or decreasing compared to vehicle. Genes exhibiting
this pattern included Wnt inhibitors Sost and Dkk1, though both had been up
regulated until the end of dosing in Cn OCy. Changes in cell cycle genes such as
Cdkn1a and Ndrg1 in Ct OCy suggested up-regulation of p53 signaling, as observed
in Cn OCy; however, unlike in Cn bone, p53 signaling was not associated with
decreased bone formation and was absent at day 183, when bone formation began to
decline on the Ec surface. These data demonstrate involvement of similar
molecular pathways in Ct and Cn bone in response to Scl-Ab but with a different
temporal relationship to bone formation and suggest that the specific mechanism
underlying self-regulation of Scl-Ab-induced bone formation may be different
between Cn and Ct bone.
PMID- 29955629
TI - Denosumab significantly improves lumbar spine bone mineral density more in
treatment-naive than in long-term bisphosphonate-treated patients.
AB - The purpose of our study was to compare the skeletal responses to 3-year
denosumab treatment in bisphosphonate (BP)-naive and long-term BP-treated
patients with postmenopausal osteoporosis. Female patients who were BP treatment
naive (treatment-naive group: 25 cases) or who received long-term BPs (BP pre
treated group: 24 cases) were compared for serum bone alkaline phosphatase (BAP),
tartrate-resistant acid phosphatase (TRACP)-5b, and urinary N-terminal
telopeptide of type I collagen (NTX) at baseline and at 4, 8, 12, 15, 18, 21, 24,
27, 30, 33, and 36 months of denosumab therapy. Lumbar 1-4 (L) spine bone mineral
density (BMD), total hip (H)-BMD, and femoral neck (FN)-BMD values were measured
at baseline and at 4, 8, 12, 18, 24, 30, and 36 months. The percentage changes of
bone turnover markers were significantly decreased throughout the study period by
a larger margin in the treatment-naive group than in the BP pre-treated group. L
BMD, H-BMD, and FN-BMD were all significantly increased in the treatment-naive
and BP pre-treated groups at 36 months (12.9% and 7.5%, 5.9% and 6.0%, and 7.6%
and 4.5%, respectively), compared with pre-treatment levels. There were
significant differences for L-BMD at 12, 24, 30, and 36 months between the
groups. Our findings suggest that the BMD response to denosumab, especially that
of L-BMD, was diminished following BP therapy relative to treatment-naive
patients, thus providing evidence supporting the use of denosumab as a first-line
therapy.
PMID- 29955628
TI - Bisphosphonate-related osteonecrosis of the jaw: a mechanobiology perspective.
AB - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a dramatic
disintegration of the jaw that affects patients treated with bisphosphonates
(BPs) for diseases characterized by bone loss. These diseases are often
metastasizing cancers (like multiple myeloma, breast cancer and prostate cancer
(Aragon-Ching et al., 2009)) as well as osteoporosis. BRONJ is incompletely
understood, although it is believed to arise from a defect in bone remodeling-the
intricate process by which sensory osteocytes signal to osteoclasts and
osteoblasts to resorb and form bone in response to stimuli. Further, tooth
extraction and infection have been overwhelmingly linked to BRONJ (Ikebe, 2013).
Because bone cells are highly networked, the importance of multicellular
interactions and mechanotransduction during the onset of these risk factors
cannot be overstated. As such, this perspective addresses current research on the
effects of BPs, mechanical load and inflammation on bone remodeling and on
development of BRONJ. Our investigation has led us to conclude that improved in
vitro systems capable of adequately recapitulating multicellular communication
and incorporating effects of osteocyte mechanosensing on bone resorption and
formation are needed to elucidate the mechanism(s) by which BRONJ ensues.
PMID- 29955630
TI - Effect of osteoporosis treatment agents on the cortical bone osteocyte
microenvironment in adult estrogen-deficient, osteopenic rats.
AB - Though osteoporosis is a significant cause of disability worldwide, treatment
with pharmacologic agents decreases risk of fragility fracture. Though these
treatments act through the bone remodeling system to improve bone mass, it is
unclear if they alter the response of bone to mechanical loading at the level of
the osteocyte. This pre-clinical study determined the relationship between
microstructural bone tissue properties and osteocyte lacunar size and density to
strain around osteocytes with standard osteoporosis treatment or sequential
therapies. Six-month-old female ovariectomized (OVX) Sprague-Dawley rats were
cycled through various sequences of pharmacological treatments [alendronate
(Aln), raloxifene (Ral) and human parathyroid hormone-1,34 (PTH)] for three month
intervals, over nine months. Linear nanoindentation mapping was used to determine
Young's modulus in perilacunar and bone matrix regions around cortical bone
osteocyte lacunae. Measurements of lacunar diameter and density were completed.
Treatment-related differences in Young's modulus in the perilacunar and bone
matrix regions were not observed. We confirmed previous data that showed that the
bone matrix region was stiffer than the perilacunar matrix region. Whole bone
material properties were correlated to perilacunar matrix stiffness. Finite
element models predicted a range of mechanical strain amplification factors
estimated at the osteocyte across treatment groups. In summary, though the
perilacunar matrix near cortical osteocyte lacuna is not as stiff as bone matrix
further away, osteoporosis treatment agents do not affect the stiffness of bone
tissue near osteocyte lacunae.
PMID- 29955631
TI - Bone histomorphometry in the evaluation of osteomalacia.
AB - With the widespread use of measurement of bone mineral density to detect,
diagnose, and monitor therapy in the management of osteoporosis, bone
histomorphometry has largely been relegated to research settings and academic
pursuits. However, bone density measurement cannot distinguish between
osteoporosis and other metabolic bone disorders such as different types of
osteomalacia, osteitis fibrosa, renal osteodystrophy, hypophosphatasia, and
Paget's disease of bone. Furthermore, bone density test cannot tell us anything
about microarchitecture of bone, tissue level dynamics, bone cellular activity,
bone mineralization and bone remodeling, understanding of which is essential to
make a specific diagnosis of a suspected metabolic bone disease, to evaluate
beneficial (or adverse) effects of various therapies, treatment (medical or
surgical) decisions in hyperparathyroid states. As a research tool, bone
histomorphometry contributed immensely to our understanding of bone biology,
revolutionized the study of the mechanism of actions of various therapies, and
provided crucial understanding of the adverse effects of drugs.
PMID- 29955633
TI - Deletion of Orai1 leads to bone loss aggravated with aging and impairs function
of osteoblast lineage cells.
AB - Osteoblast lineage cells, a group of cells including mesenchymal progenitors,
osteoblasts, and osteocytes, are tightly controlled for differentiation,
proliferation and stage-specific functions in processes of skeletal development,
growth and maintenance. Recently, the plasma membrane calcium channel Orai1 was
highlighted for its role in skeletal development and osteoblast differentiation.
Yet the roles of Orai1 in osteoblast lineage cells at various stages of
maturation have not been investigated. Herein we report the severe bone loss that
occurred in Orai1-/- mice, aggravated by aging, as shown by the microcomputed
tomography (mCT) and bone histomorphometry analysis of 8-week and 12-week old
Orai1-/- mice and sex-matched WT littermates. We also report that Orai1
deficiency affected the differentiation, proliferation, and type I collagen
secretion of primary calvarial osteoblasts, mesenchymal progenitors, and
osteocytes in Orai1-/- mice; specifically, our study revealed a significant
decrease in the expression of osteocytic genes Fgf23, DMP1 and Phex in the
cortical long bone of Orai1-/- mice; a defective cellular and nuclear morphology
of Orai1-/- osteocytes; and defective osteogenic differentiation of Orai1-/-
primary calvarial osteoblasts (pOBs), including a decrease in extracellular
secretion of type I collagen. An increase in the mesenchymal progenitor
population of Orai1-/- bone marrow cells was indicated by a colony forming unit
fibroblasts (CFU-F) assay, and the increased proliferation of Orai1-/- pOBs was
indicated by an MTT assay. Notably, Orai1 deficiency reduced the nuclear
localization and transcription activity of the Nuclear Factor of Activated T-cell
c1 (NFATc1), a calcium-regulated transcription factor, in pOBs. Altogether, our
study demonstrated the crucial role of Orai1 in bone development and maintenance,
via its diverse effects on osteoblast lineage cells from mesenchymal progenitors
to osteocytes.
PMID- 29955632
TI - Vitamin D in the Middle East and North Africa.
AB - Purpose: The Middle East and North Africa (MENA) region registers some of the
lowest serum 25-hydroxyvitamin D [25(OH)D] concentrations, worldwide. We describe
the prevalence and the risk factors for hypovitaminosis D, completed and ongoing
clinical trials, and available guidelines for vitamin D supplementation in this
region. Methods: This review is an update of previous reviews published by our
group in 2013 for observational studies, and in 2015 for randomized controlled
trials (RCTs) from the region. We conducted a comprehensive search in Medline,
PubMed, and Embase, and the Cochrane Library, using MeSH terms and keywords
relevant to vitamin D, vitamin D deficiency, and the MENA region, for the period
2012-2017 for observational studies, and 2015-2017 for RCTs. We included large
cross-sectional studies with at least 100 subjects/study, and RCTs with at least
50 participants per arm. Results: We identified 41 observational studies. The
prevalence of hypovitaminosis D, defined as a 25-hydroxyvitamin D [25(OH)D] level
below the desirable level of 20 ng/ml, ranged between 12-96% in children and
adolescents, and 54-90% in pregnant women. In adults, it ranged between 44 and
96%, and the mean 25(OH)D varied between 11 and 20 ng/ml. In general, significant
predictors of low 25(OH)D levels were female gender, increasing age and body mass
index, veiling, winter season, use of sun screens, lower socioeconomic status,
and higher latitude.We retrieved 14 RCTs comparing supplementation to control or
placebo, published during the period 2015-2017: 2 in children, 8 in adults, and 4
in pregnant women. In children and adolescents, a vitamin D dose of 1000-2000
IU/d was needed to maintain serum 25(OH)D level at target. In adults and pregnant
women, the increment in 25(OH)D level was inversely proportional to the dose,
ranging between 0.9 and 3 ng/ml per 100 IU/d for doses <=2000 IU/d, and between
0.1 and 0.6 ng/ml per 100 IU/d for doses >=3000 IU/d. While the effect of vitamin
D supplementation on glycemic indices is still controversial in adults, vitamin D
supplementation may be protective against gestational diabetes mellitus in
pregnant women. In the only identified study in the elderly, there was no
significant difference between 600 IU/day and 3750 IU/day doses on bone mineral
density. We did not identify any fracture studies.The available vitamin D
guidelines in the region are based on expert opinion, with recommended doses
between 400 and 2000 IU/d, depending on the age category, and country.
Conclusion: Hypovitaminosis D is prevalent in the MENA region, and doses of 1000
2000 IU/d may be necessary to reach a desirable 25(OH)D level of 20 ng/ml.
Studies assessing the effect of such doses of vitamin D on major outcomes, and
confirming their long term safety, are needed.
PMID- 29955634
TI - Autism and heritable bone fragility: A true association?
AB - Objectives: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly
characterised by bone fragility; intelligence is reported to be normal. However,
a minority of children seen also show symptomology consistent with an 'Autism
Spectrum Disorder'. A joint genetics and psychology research study was undertaken
to identify these patients using 'Gold Standard' research tools: Autism
Diagnostic Inventory Revised (ADI-R); Autism Diagnostic Observation Schedule
(ADOS) and undertake genetic analyses in them. Method: A cohort of n = 7 children
with autistic traits and severe/complex OI were recruited to the study. The study
was set-up to explore whether there was a genetic link between bone fragility and
autism in a sub-set of patients with bone fragility identified with autism traits
in our complex/severe OI clinic. This was not set-up as a prevalence study but
rather an exploration of genetics in association with ADI/ADOS confirmed ASD and
bone fragility. ADI& ADOS: Standardised tools were used to confirm autism
diagnosis. ADI and ADOS were completed by the Clinical Psychologist; ADI
comprises a 93 item semi-structured clinical review with a diagnostic algorithm
diagnosing Autism; ADOS is a semi-structured assessment of socialisation,
communication and play/imagination which also provides a diagnostic algorithm.
Exome sequencing: In patients recruited, those that fulfilled research criteria
for diagnosis of autism using above tools were recruited to trio whole exome
sequencing (WES). Results: one patient had compound heterozygous variants in
NBAS; one patient had a variant in NRX1; one patient had a maternally inherited
PLS3 variant; all the other patients in this cohort had pathogenic variants in
COL1A1/COL1A2. Conclusions: Although, not set out as an objective, we were able
to establish that identifying autism had important clinical and social benefits
for patients and their families in ensuring access to services, appropriate
schooling, increased understanding of behaviour and support. Lay summary: It is
important for clinicians looking after children with brittle bone disease, also
referred to as Osteogenesis Imperfecta (OI) to be aware of early features of
developmental delay/autistic traits especially with severe forms of OI as the
emphasis is on their mobility and bone health. Ensuring appropriate assessment
and access to services early-on will enable these patients to achieve their
potential. Further investigations of genomics in bone fragility in relation to
autism are required and dual diagnosis is essential for high quality clinical and
educational provision.
PMID- 29955635
TI - Adults with osteogenesis imperfecta: Clinical characteristics of 151 patients
with a focus on bisphosphonate use and bone density measurements.
AB - An expert center for adults with Osteogenesis Imperfecta (OI) has been founded at
the Isala Hospital in Zwolle, the Netherlands to achieve optimal care for adults
with OI. Clinical data such as patient history, Dual Energy X-ray Absorptiometry
measurements and laboratory findings are collected with patient consent. This
study provides an overview of clinical characteristics of the patients who
visited the clinic during its first 5 years, a total of 151 patients. In this
study, we focus on bisphosphonate use and bone density measurements at time of
presentation at the expert center. As such, insight into the natural history of
OI in adults will be increased. Analysing the data of a large group of adults
with this rare disorder within a national expert center will allow detailed
exploration of the course of OI over time.
PMID- 29955636
TI - Effect of temporal onsets of mechanical loading on bone formation inside a tissue
engineering scaffold combined with cell therapy.
AB - Several approaches to combine bone substitutes with biomolecules, cells or
mechanical loading have been explored as an alternative to the limitation and
risk-related bone auto- and allo-grafts. In particular, human bone progenitor
cells seeded in porous poly(L-lactic acid)/tricalcium phosphate scaffolds have
shown promising results. Furthermore, the application of mechanical loading has
long been known to be a key player in the regulation of bone architecture and
mechanical properties. Several in vivo studies have pointed out the importance of
its temporal offset. When an early mechanical loading was applied a few days
after scaffold implantation, it was ineffective on bone formation, whereas a
delayed mechanical loading of several weeks was beneficial for bone tissue
regeneration. No information is reported to date on the effectiveness of applying
a mechanical loading in vivo on cell-seeded scaffold with respect to bone
formation in a bone site. In our study, we were interested in human bone
progenitor cells due to their low immunogenicity, sensitivity to mechanical
loading and capacity to differentiate into osteogenic human bone progenitor
cells. The latest capacity allowed us to test two different bone cell fates
originating from the same cell type. Therefore, the general aim of this study was
to assess the outcome on bone formation when human bone progenitor cells or pre
differentiated osteogenic human bone progenitor cells are combined with early and
delayed mechanical loading inside bone tissue engineering scaffolds. Scaffolds
without cells, named cell-free scaffold, were used as control. Surprisingly, we
found that (1) the optimal solution for bone formation is the combination of cell
free scaffolds and delayed mechanical loading and that (2) the timing of the
mechanical application is crucial and dependent on the cell type inside the
implanted scaffolds.
PMID- 29955637
TI - The reproducibility of measuring trabecular bone parameters using a commercially
available high-resolution magnetic resonance imaging approach: A pilot study.
AB - Bone imaging is currently the best non-invasive way to assess changes to bone
associated with aging or chronic disease. However, common imaging techniques such
as dual energy x-ray absorptiometry are associated with limitations. Magnetic
resonance imaging (MRI) is a radiation-free technique that can measure bone
microarchitecture. However, published MRI bone assessment protocols use
specialized MRI coils and sequences and therefore have limited transferability
across institutions. We developed a protocol on a Siemens 3 Tesla MRI machine,
using a commercially available coil (Siemens 15 CH knee coil), and manufacturer
supplied sequences to acquire images at the tibia. We tested the reproducibility
of the FSE and the GE Axial sequences and hypothesized that both would generate
reproducible trabecular bone parameters. Eight healthy adults (age 25.5 +/- 5.4
years) completed three measurements of each MRI sequence at the tibia. Each of
the images was processed for 8 different bone parameters (such as volumetric bone
volume fraction). We computed the coefficient of variation (CV) and intraclass
correlation coefficients (ICC) to assess reproducibility and reliability. Both
sequences resulted in trabecular parameters that were reproducible (CV <5% for
most) and reliable (ICC >80% for all). Our study is one of the first to report
that a commercially available MRI protocol can result in reproducible data, and
is significant as MRI may be an accessible method to measure bone
microarchitecture in clinical or research environments. This technique requires
further testing, including validation and evaluation in other populations.
PMID- 29955638
TI - Roles of plasminogen in the alterations in bone marrow hematopoietic stem cells
during bone repair.
AB - We previously revealed that stromal cell-derived factor-1 (SDF-1) is involved in
the changes in the number of bone marrow stem cells during the bone repair
process in mice. Moreover, we reported that plasminogen (Plg) deficiency delays
bone repair and the accumulation of macrophages at the site of bone damage in
mice. We investigated the roles of Plg in the changes in bone marrow stem cells
during bone repair. We analyzed the numbers of hematopoietic stem cells (HSC) and
mesenchymal stem cells (MSCs) within bone marrow from Plg-deficient and wild-type
mice after a femoral bone injury using flow cytometric analysis. Plg deficiency
significantly blunted a decrease in the number of HSCs after bone injury in mice,
although it did not affect an increase in the number of MSCs. Plg deficiency
significantly blunted the number of SDF-1- and Osterix- or SDF-1- and alkaline
phosphatase-double-positive cells in the endosteum around the lesion as well as
matrix metalloprotainase-9 (MMP-9) activity and mRNA levels of SDF-1 and
transforming growth factor-beta (TGF-beta) elevated by bone injury. TGF-beta
signaling inhibition significantly blunted a decrease in the number of HSCs after
bone injury. The present study showed that Plg is critical for the changes in
bone marrow HSCs through MMP-9, TGF-beta, and SDF-1 at the damaged site during
bone repair in mice.
PMID- 29955639
TI - Differential effects of high fat diet and diet-induced obesity on skeletal
acquisition in female C57BL/6J vs. FVB/NJ Mice.
AB - The effects of obesity on bone metabolism are complex, and may be mediated by
consumption of a high fat diet and/or by obesity-induced metabolic dysregulation.
To test the hypothesis that both high fat (HF) diet and diet-induced metabolic
disease independently decrease skeletal acquisition, we compared effects of HF
diet on bone mass and microarchitecture in two mouse strains: diet-induced
obesity (DIO)-susceptible C57BL/6J (B6) and DIO-resistant FVB/NJ (FVB). At 3 wks
of age we weaned 120 female FVB and B6 mice onto normal (N, 10% Kcal/fat) or HF
diet (45% Kcal/fat) and euthanized them at 6, 12 and 20 weeks of age (N =
10/grp). Outcomes included body mass; percent fat and whole-body bone mineral
density (WBBMD, g/cm2) via DXA; cortical and trabecular bone architecture at the
midshaft and distal femur via MUCT; and marrow adiposity via histomorphometry. In
FVB HF, body mass, percent body fat, WBBMD and marrow adiposity did not differ
vs. N, but trabecular bone mass was lower at 6 wks of age only (p < 0.05),
cortical bone geometric properties were lower at 12 wks only, and bone strength
was lower at 20 wks of age only in HF vs. N (p < 0.05). In contrast, B6 HF had
higher body mass, percent body fat, and leptin vs. N. B6 HF also had higher WBBMD
(p < 0.05) at 9 and 12 wks of age but lower distal femur trabecular bone mass at
12 wks of age, and lower body mass-adjusted cortical bone properties at 20 wks of
age compared to N (p < 0.05). Marrow adiposity was also markedly higher in B6 HF
vs. N. Overall, HF diet negatively affected bone mass in both strains, but was
more deleterious to trabecular bone microarchitecture and marrow adiposity in B6
than in FVB mice. These data suggest that in addition to fat consumption itself,
the metabolic response to high fat diet independently alters skeletal acquisition
in obesity.
PMID- 29955640
TI - Skeletal vascular perfusion is altered in chronic kidney disease.
AB - Patients with chronic kidney disease (CKD) are at an alarming risk of
cardiovascular disease and fracture-associated mortality. CKD has been shown to
have negative effects on vascular reactivity and organ perfusion. Although
alterations in bone blood flow are linked to dysregulation of bone remodeling and
mass in multiple conditions, changes to skeletal perfusion in the setting of CKD
have not been explored. The goal of this study was to establish the effect of CKD
on skeletal perfusion in a rat model of CKD. In two experiments with endpoints at
30 and 35 weeks of age, respectively, normal (NL) and Cy/+ (CKD) animals (n =
6/group) underwent in vivo intra-cardiac fluorescent microsphere injection to
assess bone tissue perfusion. These two separate time points aimed to describe
skeletal perfusion at 30 and 35 weeks based on previous studies demonstrating
significant progression of hyperparthyroid bone disease during this timeframe.
CKD animals had blood urea nitrogen (BUN) levels significantly higher than NL at
both 30 and 35 weeks. At 30 weeks, perfusion was significantly higher in the
femoral cortex (+259%, p < 0.05) but not in the tibial cortex (+140%, p = 0.11)
of CKD animals relative to NL littermates. Isolated tibial marrow perfusion at 30
weeks showed a trend toward being higher (+183%, p = 0.08) in CKD. At 35 weeks,
perfusion was significantly higher in both the femoral cortex (+173%, p < 0.05)
and the tibial cortex (+241%, p < 0.05) in CKD animals when compared to their
normal littermates. Isolated tibial marrow perfusion (-57%, p <0.05) and
vertebral body perfusion (-71%, p <0.05) were lower in CKD animals. The current
study demonstrates two novel findings regarding bone perfusion in an animal model
of high turnover CKD. First, cortical bone perfusion in CKD animals is higher
than in normal animals. Second, alterations in bone marrow perfision differed
among the stages of CKD and were distinct from perfusion to the cortical bone.
Determining whether these changes in bone perfusion are drivers, propagators, or
consequences of skeletal deterioration in CKD will necessitate further work.
PMID- 29955641
TI - A methodology for the generation and non-destructive characterisation of
transverse fractures in long bones.
AB - Long bone fractures are common and although treatments are highly effective in
most cases, it is challenging to achieve successful repair for groups such as
open and periprosthetic fractures. Previous biomechanical studies of fracture
repair, including computer and experimental models, have simplified the fracture
with a flat geometry or a gap, and there is a need for a more accurate fracture
representation to mimic the situation in-vivo. The aims of this study were to
develop a methodology for generating repeatable transverse fractures in long
bones in-vitro and to characterise the fracture surface using non-invasive
computer tomography (CT) methods. Ten porcine femora were fractured in a custom
built rig under high-rate loading conditions to generate consistent transverse
fractures (angle to femoral axis < 30 degrees). The bones were imaged using high
resolution peripheral quantitative CT (HR-pQCT). A method was developed to
extract the roughness and form profiles of the fracture surface from the image
data using custom code and Guassian filters. The method was tested and validated
using artificially generated waveforms. The results revealed that the smoothing
algorithm used in the script was robust but the optimum kernel size has to be
considered.
PMID- 29955642
TI - Bone development in growing female mice fed calcium and vitamin D at lower levels
than is present in the AIN-93G reference diet.
AB - Background: The AIN-93G reference (REF) diet is used to allow the comparison
within and between studies of different research groups but its levels of vitamin
D (vit D) and calcium (Ca) may be higher than required for healthy bone structure
and bone mineral density (BMD). Objective: To determine if lower dietary levels
of Ca (3.5, 3 or 2.5 g Ca/kg diet) at 1 of 2 levels of vit D (100 or 400 IU/kg
diet) supports similar development of bone structure and BMD compared to AIN-93G
reference (REF) diet in female CD-1 mice at 2 and 4 months of age. Methods:
Within a trial, weanling female mice (n = 12-15/group) were randomized to 1 of 4
diets until necropsy at 4 months of age: Trial 1: 100 IU vit D/kg + 3.5, 3 or 2.5
g Ca/kg diet or 1000 IU vit D/kg + 5 g Ca/kg diet (REF); and Trial 2: 400 IU vit
D/kg + 3.5, 3 or 2.5 g Ca/kg diet or 1000 IU vit D/kg + 5 g/kg diet (REF). At age
2 and 4 months, in vivo bone structure and BMD were assessed using micro-computed
tomography (MUCT) at the proximal and midpoint tibia. At age 4 months, lumbar
vertebra 4 (L4) and mandible structure were analyzed ex vivo, femur strength at
midpoint and neck was assessed and serum 25(OH)D3 and PTH were quantified.
Results: For Trial 1 (100 IU vit D/kg), there were no differences in tibia
structure at age 2 and 4 months nor L4 or mandible structure or femur strength at
the midpoint or neck at 4 months of age despite lower serum 25(OH)D3 among all
groups compared to REF. For Trial 2 (400 IU vit D/kg), mice fed 2.5 g Ca/kg diet
had lower (p < 0.05) Ct.Ar/Tt.Ar and Ct.Th at the tibia midpoint compared to REF.
Furthermore, Ct.Th. was greater in REF and 3.5 g Ca/kg diet compared to 2.5 g
Ca/kg diet at age 2 but not 4 months of age. At L4, BV/TV was lower (p < 0.05) in
the 3 g Ca/kg diet group compared to REF at age 4 months. There were no
differences among groups for serum 25(OH)D3 or femur strength at the midpoint or
neck. Serum PTH was not elevated compared to REF in either Trial. Conclusion:
Lowering both dietary vit D (100 IU/kg) and Ca (2.5 g/kg) in AIN-93G diet did not
result in differences in bone development of female CD-1 mice at early adulthood.
Translational relevance of bone studies conducted using the AIN-93G diet may be
affected by its high vit D and Ca content.
PMID- 29955643
TI - Evaluation of the long-term skeletal effect induced by teratogen 5-aza
2'deoxycytidine on offspring of high (C3H/HeJ) and low (C57BL/6J) bone mass
phenotype mice.
AB - The long term skeletal effects of antenatal exposure to teratogen 5-deoxy-2'
cytidine (5-AZA) were studied using two inbred strains, C3H/HeJ (C3H, with
inherently stronger bones) and C57Bl/6J (C57, with weaker bones). We previously
reported that in-utero exposure to 5-AZA resulted in loss of bone quality in 3-
and 6-mo-old C3H offspring. In this study, we further examined whether the long
term effects of an acute teratogenic exposure are still evident in older mice.
Bone phenotypes of 12 mo-old mice exposed to a single injection of 5-AZA on day
10 of their mother's pregnancy were evaluated by micro-computed tomography and
compared to the untreated controls. The main observation of this study is that 5
AZA-induced loss of bone length was registered in 12-mo-old C57 and C3H males. As
expected, we did not find differences in the 3rd lumbar vertebra since in-utero
exposure to 5-AZA was shown to affect the limb buds but not the axial skeleton.
Trajectory of changes in bone phenotypes from ages 3 mo through 6 mo to 12 mo was
also compared; 5-AZA-exposed C57 males had consistently lower femoral length and
trabecular BMD than age-matched controls. In summary, by characterizing teratogen
exposed C57 and C3H mice, we further confirmed that the adaptive response to
antenatal insults continue into mid-life of the mice as well as there is a sex
specificity of these responses.
PMID- 29955644
TI - 10 years of 25-hydroxyvitamin-D testing by LC-MS/MS-trends in vitamin-D
deficiency and sufficiency.
AB - In early 2000's vitamin-D deficiency was shown to be prevalent in several
countries including the United States (US). Studies exploring the role of vitamin
D metabolism in diverse disease pathways generated an increased demand for
vitamin-D supplementation and an immense public interest in measurement of
vitamin-D metabolite levels. In this report, we review the role of vitamin-D
metabolism in disease processes, clinical utility of measuring vitamin-D
metabolites including 25-hydroxyvitamin-D (25(OH)D), 1,25-dihydroxyvitamin-D and
24,25-dihydroxyvitamin-D and discuss vitamin-D assay methodologies including
immunoassays and liquid chromatography mass spectrometry (LC-MS/MS) assays. We
also provide examples of vitamin-D toxicity and insight into the trends in serum
25(OH)D levels in the US population based on 10 years of data from on serum
25(OH)D values from ~5,000,000 patients who were tested at the Mayo Medical
Laboratories between February 2007-February 2017.
PMID- 29955646
TI - Severe recalcitrant morbilliform eruption from dual immune checkpoint blockade.
PMID- 29955645
TI - Metabolomics-based profiles predictive of low bone mass in menopausal women.
AB - Osteoporosis is a skeletal disorder characterized by compromised bone strength
and increased risk of fracture. Low bone mass and/or pre-existing bone fragility
fractures serve as diagnostic criteria in deciding when to start medication for
osteoporosis. Although osteoporosis is a metabolic disorder, metabolic markers to
predict reduced bone mass are unknown. Here, we show serum metabolomics profiles
of women grouped as pre-menopausal with normal bone mineral density (BMD) (normal
estrogen and normal BMD; NN), post-menopausal with normal BMD (low estrogen and
normal BMD; LN) or post-menopausal with low BMD (low estrogen and low BMD; LL)
using comprehensive metabolomics analysis. To do so, we enrolled healthy
volunteer and osteoporosis patient female subjects, surveyed them with a
questionnaire, measured their BMD, and then undertook a comprehensive
metabolomics analysis of sera of the three groups named above. We identified 24
metabolites whose levels differed significantly between NN/LN and NN/LL groups,
as well as 18 or 10 metabolites whose levels differed significantly between NN/LN
and LN/LL, or LN/LL and NN/LN groups, respectively. Our data shows metabolomics
changes represent useful markers to predict estrogen deficiency and/or bone loss.
PMID- 29955647
TI - Immediate-type infliximab infusion reaction presenting as purpura.
PMID- 29955648
TI - Person-centered care for older people with dementia in the acute hospital.
AB - Introduction: Patients with dementia (PWDs) are often subjected to enforced
dependency and experience functional decline and emotional distress during
hospital stay. Person-centered care (PCC) with specialized psychosocial
interventions, minimally obtrusive medical care, and physical restraints-free
practice holds potential to improve patient outcomes. We evaluate the
effectiveness of an acute hospital dementia unit (Care for Acute Mentally Infirm
Elders [CAMIE]) that adopts a PCC protocol. Methods: Prospective naturalistic
cohort study whereby PWDs in the CAMIE unit (n = 170) were compared with a
control group in usual care wards (n = 60) over 6 months. Assessments included
patient demographics, dementia type and stage, comorbidities (Charlson's
Comorbidity Index), acute illness severity, Well-Being, Ill-Being, functional
status (Modified Barthel Index), agitation levels (Pittsburgh Agitation Scale),
and quality of life (EuroQoL), assessed on admission and discharge. Multivariate
analysis of covariance examined the effect of CAMIE versus usual care on pre-post
outcomes. Results: CAMIE patients showed statistically significant greater gains
in Modified Barthel Index function and Well-Being, decreased Ill-Being and
agitation, and greater improvement in EuroQoL index score (effect size: Delta =
0.18) after adjusting for baseline differences that translated to a quality
adjusted life years gain of 0.045, assuming stability over 3 months. Estimating
added cost of CAMIE stay over usual care at SGD 1500 (USD 1040) for average
length of stay of 15 days per patient, the incremental cost-effectiveness ratio
fell within the threshold for cost-effectiveness at USD 23,111. Discussion: PCC
for PWDs in acute hospitals not only improves clinical outcomes for patients but
is also cost-effective. The results support the adoption of PCC on a wider scale
for better care of PWDs.
PMID- 29955649
TI - Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's
disease.
AB - Introduction: We assessed the feasibility and cognitive effects of a ketogenic
diet (KD) in participants with Alzheimer's disease. Methods: The Ketogenic Diet
Retention and Feasibility Trial featured a 3-month, medium-chain triglyceride
supplemented KD followed by a 1-month washout in clinical dementia rating (CDR)
0.5, 1, and 2 participants. We obtained urine acetoacetate, serum beta
hydroxybutyrate, food record, and safety data. We administered the Alzheimer's
Disease Assessment Scale-cognitive subscale and Mini-Mental State Examination
before the KD, and following the intervention and washout. Results: We enrolled
seven CDR 0.5, four CDR 1, and four CDR 2 participants. One CDR 0.5 and all CDR 2
participants withdrew citing caregiver burden. The 10 completers achieved
ketosis. Most adverse events were medium-chain triglyceride-related. Among the
completers, the mean of the Alzheimer's Disease Assessment Scale-cognitive
subscale score improved by 4.1 points during the diet (P = .02) and reverted to
baseline after the washout. Discussion: This pilot trial justifies KD studies in
mild Alzheimer's disease.
PMID- 29955650
TI - Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics, and
pharmacokinetics in the APP/PS1 mouse.
AB - Introduction: Translational inhibition of amyloid precursor protein (APP) by
Posiphen has been shown to reduce APP and its fragments in cell culture, animal
models, and mildly cognitively impaired patients, making it a promising drug
candidate for the treatment of Alzheimer's disease. Methods: We used a mouse
model of Alzheimer's disease (APP/presenilin-1) to examine Posiphen's efficacy,
pharmacodynamics, and pharmacokinetics. Results: Posiphen treatment normalized
impairments in spatial working memory, contextual fear learning, and synaptic
function in APP/presenilin-1 mice, without affecting their visual acuity, motor
skills, or motivation and without affecting wild-type mice. Posiphen had a
prolonged effect in reducing APP and all related peptides for at least 9 hours
after the last dose. Its concentration was higher in the brain than in plasma,
and the most abundant metabolite was N8-norPosiphen. Discussion: This is the
first study demonstrating the therapeutic efficacy of inhibiting the translation
of APP and its fragments in an Alzheimer's disease model.
PMID- 29955651
TI - A simulation study comparing slope model with mixed-model repeated measure to
assess cognitive data in clinical trials of Alzheimer's disease.
AB - Introduction: In clinical trials of Alzheimer's disease, a mixed-model repeated
measure approach often serves as the primary analysis when evaluating disease
progression; a slope model may be secondary. Methods: Longitudinal change from
baseline (14-item version of Alzheimer's Disease Assessment Scale-Cognitive
Subscale) was simulated for treatment/placebo from multivariate normal
distributions with the variance-covariance matrix estimated from solanezumab
trial data. Type I error, power, and bias were based on 18-month treatment
contrast. Sample sizes included 500 and 1000 patients/arm. Results: The slope
model was more powerful in most scenarios. Mixed-model repeated measure was
relatively unbiased in parameter estimation. The slope model yielded unbiased
estimates whenever the underlying trajectory was not detectably different from
linear. Both methods led to similar type I error. Discussion: In clinical trials
of Alzheimer's disease, mixed-model repeated measure analysis with relaxed
assumptions on disease progression seems to be preferred. The slope model might
be more powerful if the trajectory has little departure from linearity.
PMID- 29955652
TI - Neuroprotective effect of a new photobiomodulation technique against Abeta25-35
peptide-induced toxicity in mice: Novel hypothesis for therapeutic approach of
Alzheimer's disease suggested.
AB - Introduction: Photobiomodulation was assessed as a novel treatment of Alzheimer's
disease (AD) by the use of a new device RGn500 combining photonic and magnetic
emissions in a mouse model of AD. Methods: Following the injection of amyloid
beta 25-35 peptide in male Swiss mice, RGn500 was applied once a day for 7 days
either on the top of the head or the center of abdomen or both. Results: RGn500
daily application for 10 min produced a neuroprotective effect on the neurotoxic
effects of amyloid beta 25-35 peptide injection when this type of
photobiomodulation was applied both on the head and on the abdomen. Protection
was demonstrated by memory restoration and on the normalization of key markers of
AD (amyloid beta 1-42, pTau), oxidative stress (lipid peroxidation), apoptosis
(Bax/Bcl2) and neuroinflammation. Discussion: RGn500 displays therapeutic
efficacy similar to other pharmacological approaches evaluated in this model of
AD.
PMID- 29955654
TI - Efficacy and safety of the compound Chinese medicine SaiLuoTong in vascular
dementia: A randomized clinical trial.
AB - Introduction: No licensed medications are available to treat vascular dementia
(VaD). Methods: Patients were randomly assigned to experimental groups
(SaiLuoTong [SLT] 360 or 240 mg for groups A and B for 52 weeks, respectively) or
placebo group (SLT 360 mg and 240 mg for group C only from weeks 27 to 52,
respectively). Results: Three hundred twenty-five patients were included in final
analysis. At week 26, the difference in VaD Assessment Scale-cognitive subscale
scores was 2.67 (95% confidence interval, 1.54 to 3.81) for groups A versus C,
and 2.48 (1.34 to 3.62) for groups B versus C (both P < .0001). However, at week
52, no difference was observed among the groups on the VaD Assessment Scale
cognitive subscale (P = .062) because of the emerging efficacy of SLT in placebo
beginning at week 27. Discussion: This study suggests that SLT is effective for
treatment of VaD, and this compound Chinese medicine may represent a better
choice to treat VaD.
PMID- 29955653
TI - Measuring cognition and function in the preclinical stage of Alzheimer's disease.
AB - The Alzheimer's Association's Research Roundtable met in November 2016 to explore
how best to measure changes in cognition and function in the preclinical stage of
Alzheimer's disease. This review will cover the tools and instruments currently
available to identify populations for prevention trials, and measure subtle
disease progression in the earliest stages of Alzheimer's disease, and will
include discussions of suitable cognitive, behavioral, functional, composite, and
biological endpoints for prevention trials. Current prevention trials are
reviewed including TOMMOROW, Alzheimer's Prevention Initiative Autosomal Dominant
Alzheimer's Disease Trial, the Alzheimer's Prevention Initiative Generation
Study, and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's to compare
current approaches and tools that are being developed.
PMID- 29955655
TI - Virtual reality-based cognitive-motor training for middle-aged adults at high
Alzheimer's disease risk: A randomized controlled trial.
AB - Introduction: Ubiquity of Alzheimer's disease (AD) coupled with relatively
ineffectual pharmacologic treatments has spurred interest in nonpharmacologic
lifestyle interventions for prevention or risk reduction. However, evidence of
neuroplasticity notwithstanding, there are few scientifically rigorous,
ecologically relevant brain training studies focused on building cognitive
reserve in middle age to protect against cognitive decline. This pilot study will
examine the ability of virtual reality (VR) cognitive training to improve
cognition and cerebral blood flow (CBF) in middle-aged individuals at high AD
risk due to parental history. Methods: The design is an assessor-blind, parallel
group, randomized controlled trial of VR cognitive-motor training in middle-aged
adults with AD family history. The experimental group will be trained with
adaptive "real-world" VR tasks targeting sustained and selective attention,
working memory, covert rule deduction, and planning, while walking on a
treadmill. One active control group will perform the VR tasks without treadmill
walking; another will walk on a treadmill while watching scientific documentaries
(nonspecific cognitive stimulation). A passive (waitlist) control group will not
receive training. Training sessions will be 45 minutes, twice/week for 12 weeks.
Primary outcomes are global cognition and CBF (from arterial spin labeling [ASL])
at baseline, immediately after training (training gain), and 3 months post
training (maintenance gain). We aim to recruit 125 participants, including 20
passive controls and 35 in the other groups. Discussion: Current pharmacologic
therapies are for symptomatic AD patients, whereas nonpharmacologic training is
administrable before symptom onset. Emerging evidence suggests that cognitive
training improves cognitive function. However, a more ecologically valid
cognitive-motor VR setting that better mimics complex daily activities may
augment transfer of trained skills. VR training has benefited clinical cohorts,
but benefit in asymptomatic high-risk individuals is unknown. If effective, this
trial may help define a prophylactic regimen for AD, adaptable for home-based
application in high-risk individuals.
PMID- 29955656
TI - Donepezil may reduce the risk of comorbidities in patients with Alzheimer's
disease: A large-scale matched case-control analysis in Japan.
AB - Introduction: Few studies have focused on the association between donepezil and
physical comorbid conditions in Alzheimer's disease patients. Methods: We
investigated the association between donepezil prescription and the occurrences
of comorbidities in Alzheimer's disease patients, by using an electronic medical
records database which contains case-based information on approximately three
million patients from more than 60 hospitals across Japan. Results: Nine thousand
seven hundred forty-nine patients had at least one diagnosis of Alzheimer's
disease between 2001 and 2015. To test the robustness of the results, we used a
risk set sampling method, and the matched cohorts based on age, sex, comorbidity
level, and duration of illness consisted of 1406 cases and an equal number of
controls. From the multivariate logistic regression analysis adjusted for
covariance, less occurrence of physical comorbidities was associated with
donepezil prescription in the matched cohort. Discussion: Although the mechanisms
are unknown, donepezil may have positive effects on both cognition and physical
status.
PMID- 29955657
TI - "Text It" program to track falls in patients with Alzheimer's disease and
dementia.
AB - Introduction: Falls are a significant problem among older adults with Alzheimer's
disease, leading to high rates of fracture, hospitalization, and death. Tracking
falls in older adults, particularly those with cognitive impairment, is a
clinical and research challenge. Methods: This prospective pilot study evaluated
the feasibility of a text message program to track falls among patients with
dementia. We also compared this technique with the calendar method of fall data
collection. Results: There was a 96% completion rate of text messaging and 100%
of calendars; however, the text-gathered data were more accurate. Discussion: A
text-messaging platform to track falls shows promise in cognitively impaired
individuals.
PMID- 29955658
TI - Wishes and preferences for an online lifestyle program for brain health-A mixed
methods study.
AB - Introduction: Individuals with subjective cognitive decline (SCD) are at
increased risk of Alzheimer's disease and could benefit from a prevention
strategy targeting lifestyle factors. Making a program available through the
Internet gives a widespread reach at low cost, but suboptimal adherence is a
major threat to effectiveness. As a first step in developing an online lifestyle
program (OLP), we aimed to identify factors that are barriers and/or facilitators
for the use of an OLP in individuals with SCD in three European countries.
Methods: As part of the Euro-SCD project, SCD subjects were recruited at memory
clinics in the Netherlands, Germany, and Spain. We combined quantitative and
qualitative methods, using a mixed methods approach. We conducted an online 18
item survey on the preferences of SCD patients for an OLP (N = 238). In addition,
we held semi-structured interviews (N = 22) to gain in-depth understanding of
factors acting as a facilitator and/or barrier for intended use of an OLP. Audio
recordings were transcribed verbatim. Content analysis was performed. Results:
One hundred seventy-six individuals completed the survey (response rate 74%).
Almost all participants regularly use the Internet (97%). Participants reported
trustworthiness (93%), user-friendliness (91%), and up-to-date information (88%)
as main facilitators, whereas having contact with other users (26%), needing an
account (21%), and assignments (16%) were reported as barriers. Barriers differed
slightly between countries, but facilitators were largely similar. In-depth
interviews revealed that both program characteristics (e.g., trustworthiness,
user-friendliness, and personalization) and personal factors (e.g., expectancy to
receive negative feedback) are likely to influence the intended use of an OLP.
Discussion: Involving users provided in-depth understanding of factors associated
with the intended use of an OLP for brain health. Both program characteristics
and personal factors are likely to influence the use of an OLP. Based on this
input from the end-users, we will develop an OLP for individuals with SCD.
PMID- 29955660
TI - Discontinuation and nonpublication of interventional clinical trials conducted in
patients with mild cognitive impairment and Alzheimer's disease.
AB - Introduction: Discontinuation and nonpublication of interventional clinical
trials represents a waste of already scarce resources. We sought to identify the
prevalence of discontinuation and nonpublication of interventional clinical
trials conducted in patients afflicted by mild cognitive impairment and
Alzheimer's disease. Methods: We conducted a retrospective, cross-sectional study
on mild cognitive impairment and Alzheimer's disease-based interventional
clinical trials in ClinicalTrials.gov dating back to 1995. The analyzed data
included trial phase, intervention type, enrollment, and funding sources.
Fisher's exact and chi2 tests were used to determine any potential associations
between trial characteristics and completion. Results: A total of 744 studies
were identified, of which 502 (67%) were industry-sponsored ones. A total of 127
(17%) were discontinued prematurely. Of the 617 completed trials, 450 (73%) were
not published, representing approximately 66,655 participants who incurred the
risks of trial participation without subsequently contributing to the medical
literature. Similarly, there were 18,246 patients from unpublished, discontinued
trials. Of the 744 trials examined, 247 publications from 167 trials could be
identified via PubMed/MEDLINE and EMBASE searches. Most notably, the odds of
nonpublication among industry-sponsored trials were more than 75% higher than
those in studies funded by academia (odds ratio = 1.78; 95% confidence interval,
1.14-2.78; P = .01). Furthermore, industry-sponsored trials had a 50% greater
odds of study discontinuation compared with trials funded by academia (odds ratio
= 1.50; 95% confidence interval, 1.04-2.16; P = .03). Discussion: The
nonpublication of many trials and preliminary results of trials that are
discontinued early dilutes the quality and decreases the comprehensive nature of
the medical literature. This occurs in both industry and academia. Publication of
inconclusive or negative results ensures that all research activities, regardless
of outcome, contribute to global medical knowledge.
PMID- 29955659
TI - The Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease
Trial: A study of crenezumab versus placebo in preclinical PSEN1 E280A mutation
carriers to evaluate efficacy and safety in the treatment of autosomal-dominant
Alzheimer's disease, including a placebo-treated noncarrier cohort.
AB - Introduction: Autosomal-dominant Alzheimer's disease (ADAD) represents a crucial
population for identifying prevention strategies that might modify disease course
for cognitively unimpaired individuals at high imminent risk for developing
symptoms due to Alzheimer's disease (AD), that is, who have "preclinical" AD.
Crenezumab is an antiamyloid monoclonal antibody that binds monomeric and
aggregated forms of amyloid beta, with highest affinity for oligomers; it is in
development for early stages of sporadic AD and for ADAD. Methods: This is a
prospective, randomized, double-blind, placebo-controlled phase 2 study of the
efficacy of crenezumab versus placebo in asymptomatic PSEN1 E280A mutation
carriers from family kindreds with ADAD in Colombia. Participants were randomized
to receive either crenezumab or placebo for 260 weeks. The study was designed to
enroll a planned total of 300 participants, including 200 preclinical mutation
carriers (approximately 100 treatment, 100 placebo) and an additional control
group of mutation noncarriers from the same family kindreds included to mask
mutation carrier status (100 placebo only). The primary outcome is change in the
Alzheimer's Prevention Initiative ADAD Composite Cognitive Test Score from
baseline to week 260. Secondary outcomes include time to progression to mild
cognitive impairment due to AD or dementia due to AD; changes in dementia
severity, memory, and overall neurocognitive functioning; and changes in amyloid
positron emission tomography, fluorodeoxyglucose-positron emission tomography,
magnetic resonance imaging volumes, and cerebrospinal fluid levels of beta
amyloid, tau, and p-tau. Safety and tolerability are assessed. Results: Two
hundred fifty-two participants were enrolled between December 2013 and February
2017. Discussion: We describe the first large-scale, potentially label-enabling
clinical trial of a preclinical treatment for ADAD. Results from this trial will
inform on the efficacy of crenezumab for delaying onset of, slowing decline in,
or preventing cognitive impairment in individuals with preclinical ADAD and will
foster an improved understanding of AD biomarkers and their relationship to
clinical outcomes.
PMID- 29955661
TI - Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease.
AB - Introduction: We evaluated the selective M1 muscarinic positive allosteric
modulator, MK-7622, as adjunctive cognitive enhancing therapy in individuals with
Alzheimer's disease. Methods: A randomized, double-blind, proof-of-concept trial
was performed. Participants with mild-to-moderate Alzheimer's disease, being
treated with an acetylcholinesterase inhibitor, were randomized 1:1 to 45 mg of
MK-7622 or placebo for 24 weeks. Endpoints included the mean change from baseline
in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at 12
weeks and Alzheimer's Disease Cooperative Study-Activities of Daily Living
Inventory at 24 weeks. Results: Two hundred forty participants were randomized.
The trial was stopped for futility after meeting prospectively defined stopping
criteria. MK-7622 did not improve cognition at 12 weeks (group difference in ADAS
Cog11: 0.18 [95% confidence interval: -1.0 to 1.3]) or function at 24 weeks
(group difference in Alzheimer's Disease Cooperative Study-Activities of Daily
Living Inventory: 0.06 [95% confidence interval: -2.4 to 2.5]). More participants
taking MK-7622 discontinued study medication because of adverse events than those
taking placebo (16% vs 6%) and who experienced cholinergically related adverse
events (21% vs 8%). Discussion: MK-7622 (45 mg) does not improve cognition or
function when used as adjunctive therapy in mild-to-moderate Alzheimer's disease.
PMID- 29955662
TI - Lifestyle and neurodegeneration in midlife as expressed on functional magnetic
resonance imaging: A systematic review.
AB - Introduction: Lifestyle factors may influence brain health in midlife. Functional
magnetic resonance imaging is a widely used tool to investigate early changes in
brain health, including neurodegeneration. In this systematic review, we evaluate
the relationship between lifestyle factors and neurodegeneration in midlife, as
expressed using functional magnetic resonance imaging. Methods: We searched
MEDLINE, EMBASE, and PsycINFO combining subject headings and free text terms
adapted for each database. Articles were screened, and their quality was assessed
independently by two reviewers before final inclusion in the review. Results: We
screened 4116 studies and included 29 in the review. Seven lifestyle factors,
such as alcohol, cognitive training, excessive internet use, fasting, physical
training, smoking, and substance misuse, were identified in this review.
Discussion: Cognitive and physical trainings appear to be associated with a
neuroprotective effect, whereas alcohol misuse, smoking, and substance misuse
appear to be associated with neurodegeneration. Further research is required into
the effects of excessive internet use and fasting.
PMID- 29955663
TI - Alzheimer's disease drug development pipeline: 2018.
AB - Introduction: Treatments for Alzheimer's disease (AD) are needed due to the
growing number of individuals with preclinical, prodromal, and dementia forms of
AD. Drug development for AD therapies can be examined by inspecting the drug
development pipeline as represented on clinicaltrials.gov. Methods:
Clinicaltrials.gov was assessed as of January 30, 2018 to determine AD therapies
represented in phase I, phase II, and phase III. Results: There are 112 agents in
the current AD treatment pipeline. There are 26 agents in 35 trials in phase III,
63 agents in 75 trials in phase II, and 23 agents in 25 trials in phase I. A
review of the mechanisms of actions of the agents in the pipeline shows that 63%
are disease-modifying therapies, 22% are symptomatic cognitive enhancers, and 12%
are symptomatic agents addressing neuropsychiatric and behavioral changes. Trials
in phase III are larger and longer than phase II or phase I trials, particularly
those involving disease-modifying agents. Comparison with the 2017 pipeline shows
that there are four new agents in phase III, 14 in phase II, and eight in phase
I. Inspection of the use of biomarkers as revealed on clinicaltrials.gov shows
that amyloid biomarkers are used as entry criterion in 14 phase III disease
modifying agent trials and 17 disease-modifying agent trials in phase II. Twenty
one trials of disease-modifying agents in phase II did not require biomarker
confirmation for AD at trial entry. Discussion: The AD drug development pipeline
is slightly larger in 2018 than in 2017. Trials increasingly include preclinical
and prodromal populations. There is an increase in nonamyloid mechanisms of
action for drugs in earlier phases of drug development. Biomarkers are
increasingly used in AD drug development but are not used uniformly for AD
diagnosis confirmation.
PMID- 29955664
TI - Established amyloid-beta pathology is unaffected by chronic treatment with the
selective serotonin reuptake inhibitor paroxetine.
AB - Introduction: Treatment with selective serotonin reuptake inhibitors has been
suggested to mitigate amyloid-beta (Abeta) pathology in Alzheimer's disease, in
addition to an antidepressant mechanism of action. Methods: We investigated
whether chronic treatment with paroxetine, a selective serotonin reuptake
inhibitor, mitigates Abeta pathology in plaque-bearing double-transgenic amyloid
precursor protein (APP)swe/presenilin 1 (PS1)DeltaE9 mutants. In addition, we
addressed whether serotonin depletion affects Abeta pathology. Treatments were
assessed by measurement of serotonin transporter occupancy and high-performance
liquid chromatography. The effect of paroxetine on Abeta pathology was evaluated
by stereological plaque load estimation and Abeta42/Abeta40 ratio by enzyme
linked immunosorbent assay. Results: Contrary to our hypothesis, paroxetine
therapy did not mitigate Abeta pathology, and depletion of brain serotonin did
not exacerbate Abeta pathology. However, chronic paroxetine therapy increased
mortality in APPswe/PS1DeltaE9 transgenic mice. Discussion: Our results question
the ability of selective serotonin reuptake inhibitor therapy to ameliorate
established Abeta pathology. The severe adverse effect of paroxetine may
discourage its use for disease-modifying purposes in Alzheimer's disease.
PMID- 29955666
TI - Digital technologies as biomarkers, clinical outcomes assessment, and recruitment
tools in Alzheimer's disease clinical trials.
AB - Digital technology is transforming the development of drugs for Alzheimer's
disease and was the topic of the Alzheimer's Association's Research Roundtable on
its May 23-24, 2017 meeting. Research indicates that wearable devices and
unobtrusive passive sensors that enable the collection of frequent or continuous,
objective, and multidimensional data during daily activities may capture subtle
changes in cognition and functional capacity long before the onset of dementia.
The potential to exploit these technologies to improve clinical trials as both
recruitment and retention tools as well as for potential end points was
discussed. The implications for the collection and use of large amounts of data,
lessons learned from other related disease areas, ethical concerns raised by
these new technologies, and regulatory issues were also covered in the meeting.
Finally, the challenges and opportunities of these new technologies for future
use were discussed.
PMID- 29955667
TI - From information to follow-up: Ethical recommendations to facilitate the
disclosure of amyloid PET scan results in a research setting.
AB - In the field of Alzheimer's disease research, the use of biomarkers such as
amyloid positron emission tomography (PET) has become widespread over a
relatively brief period of time. There is an increasing tendency in research
studies and trials to switch from no disclosure under any condition toward a
qualified disclosure of individual research results, such as amyloid PET scan
results. This perspective article aims to evaluate the possible need for a
modification of the available recommendations on amyloid PET scan disclosure,
based on recent empirical evidence obtained within the field of amyloid PET. This
article also applies the International Guideline for Good Clinical Practice to
the field of amyloid PET disclosure. Hence, we propose several recommendations to
facilitate amyloid PET disclosure while minimizing possible risks of amyloid
disclosure in a research context.
PMID- 29955665
TI - Neural correlates of episodic memory in the Memento cohort.
AB - Introduction: The free and cued selective reminding test is used to identify
memory deficits in mild cognitive impairment and demented patients. It allows
assessing three processes: encoding, storage, and recollection of verbal episodic
memory. Methods: We investigated the neural correlates of these three memory
processes in a large cohort study. The Memento cohort enrolled 2323 outpatients
presenting either with subjective cognitive decline or mild cognitive impairment
who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose
positron emission tomography evaluations. Results: Encoding was associated with a
network including parietal and temporal cortices; storage was mainly associated
with entorhinal and parahippocampal regions, bilaterally; retrieval was
associated with a widespread network encompassing frontal regions. Discussion:
The neural correlates of episodic memory processes can be assessed in large and
standardized cohorts of patients at risk for Alzheimer's disease. Their relation
to pathophysiological markers of Alzheimer's disease remains to be studied.
PMID- 29955669
TI - Building medical knowledge from real world registries: The case of heart failure.
PMID- 29955668
TI - Utilisation of real-world data from heart failure registries in OECD countries -
A systematic review.
AB - Background: Heart failure represents a major public health issue that impacts 26
million people globally. Currently, real-world data represents a key instrument
for providing the verification of both internal and external validity, yet there
is still a lack of understanding regarding its scope in complementing evidence of
treatments for heart failure. This study aims to increase understanding of the
utilisation of real-word data from heart failure registries in Organisation for
Economic Co-operation and Development (OECD) countries. Method: This was a
systematic review of existing observational studies from heart failure registries
in 35 OECD member countries. Studies from 2000 to March 2017 were identified
through electronic databases (MEDLINE (Ovid), EMBASE, Web of Science Core
Collection, CINAHL (Ebsco), Cochrane CENTRAL) and appraised according to
eligibility criteria. Results: Two-hundred and two studies met the inclusion
criteria, in which the majority were published from 2013 to 2016. All 202 studies
were observational, among which 98% were cohort studies (198). The median sample
size of all studies was 5152 (2417 to 32,890) and median study period 55 months
(33.0 to 72.0). Swedish heart failure registry had the most publications (24,
12%). Conclusion: Since 2000 there has been an upward trend in the number of
published observational studies on heart failure registries in OECD countries
with increasingly diverse outcomes and advanced statistical methods to improve
their validity and reliability. This indicates that the utilisation of real-world
data has experienced a significant upsurge in complementing the findings of
clinical trials for improved research of heart failure treatments.
PMID- 29955670
TI - Can cystatin C-based estimated glomerular filtration rate help to guide
individualized risk factor modification programs?
PMID- 29955671
TI - Implementing STEADI in Academic Primary Care to Address Older Adult Fall Risk.
AB - Background and Objectives: Falls are the leading cause of injury-related deaths
in older adults. Objectives include describing implementation of the Centers for
Disease Control and Prevention's Stopping Elderly Accidents, Deaths, and Injuries
(STEADI) initiative to help primary care providers (PCPs) identify and manage
fall risk, and comparing a 12-item and a 3-item fall screening questionnaire.
Design and Methods: We systematically incorporated STEADI into routine patient
care via team training, electronic health record tools, and tailored clinic
workflow. A retrospective chart review of patients aged 65 and older who received
STEADI measured fall screening rates, provider compliance with STEADI (high-risk
patients), results from the 12-item questionnaire (Stay Independent), and
comparison with a 3-item subset of this questionnaire (three key questions).
Results: Eighteen of 24 providers (75%) participated, screening 773 (64%)
patients over 6 months; 170 (22%) were high-risk. Of these, 109 (64%) received
STEADI interventions (gait, vision, and feet assessment, orthostatic blood
pressure measurement, vitamin D, and medication review). Providers intervened on
85% with gait impairment, 97% with orthostatic hypotension, 82% with vision
impairment, 90% taking inadequate vitamin D, 75% with foot issues, and 22% on
high-risk medications. Using three key questions compared to the full Stay
Independent questionnaire decreased screening burden, but increased the number of
high-risk patients. Discussion and Implications: We successfully implemented
STEADI, screening two-thirds of eligible patients. Most high-risk patients
received recommended assessments and interventions, except medication reduction.
Falls remain a substantial public health challenge. Systematic implementation of
STEADI could help clinical teams reduce older patient fall risks.
PMID- 29955672
TI - Latent topics resonance in scientific literature and commentaries: evidences from
natural language processing approach.
AB - Resonance is generally used as a metaphor to describe the manner how the
information from different sources is combined. Although it is an attractive and
fundamental phenomenon in human behavior studies, most studies observed semantic
resonances in well-controlled experimental settings at word level. To make up the
missing link between word and document level resonances, we devoted our
contributions to topic resonances in a novel and natural setting: academic
commentaries. Ninety-three academic commentaries from ninety-three authors, along
with their references and original papers, are analyzed by a latent Dirichlet
allocation based natural language processing approach. This approach can
decompose a corpus written and read by an author into several topics with
different weights, which can reveal the phenomena ignored at word or document
level. We found that (1) topic resonances commonly exist between commenters'
fundamental input and output topics; (2) output words are re-allocated by
commenters to echo salient input topics; (3) commenters are more prone to
associate references which focus on the non-dominant input topics; and (4) topic
resonance can even be predicted by a Hebbian-like model which matches the
aforementioned findings. These findings will continue to enrich our understanding
on the relationship among probe, feedback and context.
PMID- 29955673
TI - Ulnar artery aneurysm and hypothenar hammer syndrome.
PMID- 29955674
TI - Current Developments in Nutrition: A New Journal Designed for the Open-Access
Era.
PMID- 29955675
TI - Osteoclast Differentiation is Downregulated by Select Polyphenolic Fractions from
Dried Plum via Suppression of MAPKs and Nfatc1 in Mouse C57BL/6 Primary Bone
Marrow Cells.
AB - Background: Clinical and preclinical studies have shown that dietary
supplementation with dried plum improves bone health. These osteoprotective
effects are a result, in part, of the antiresorptive properties of the fruit,
which appear to be mediated by its polyphenolic compounds. Objective: This study
was designed to determine if certain fractions of the polyphenolic compounds in
dried plums are responsible for the antiresorptive effects and whether they alter
mitogen-activated protein kinase (MAPK) and calcium signaling, which are
essential to osteoclast differentiation and activity, under normal and
inflammatory conditions. Methods: Six polyphenolic fractions were derived from
the total polyphenolic extract of dried plum based on solubility. Initial
screening, with the use of the Raw 264.7 monocyte and macrophage cell line,
showed that 3 fractions had the most marked capacity to downregulate osteoclast
differentiation. This response was confirmed in 2 of the fractions by using
primary bone marrow-derived cultures and in all subsequent experiments to
determine how osteoclast differentiation and function were altered with a focus
on these 2 fractions in primary cultures. Data were analyzed by using ANOVA
followed by post hoc analyses. Results: Both of the polyphenol fractions
decreased osteoclast differentiation and activity coincident with downregulating
nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1
(Nfatc1), which is required for osteoclast differentiation. Calcium signaling,
essential for the auto-amplification of Nfatc1, was suppressed by the
polyphenolic fractions under normal conditions as indicated by suppressed mRNA
expression of costimulatory receptors osteoclast-associated receptor (Oscar),
signaling regulatory protein beta1 (Sirpb1), and triggering receptor expressed on
myeloid cells 2 (Trem2). In contrast, in the presence of tumor necrosis factor
alpha (TNF-alpha), only Sirpb1 was downregulated. In addition to calcium
signaling, phosphorylation of extracellular signal-regulated kinase (Erk) and p38
MAPK, involved in the expression and activation of Nfatc1, was also suppressed by
the polyphenolic fractions. Conclusion: These results show that certain types of
polyphenolic compounds from dried plum downregulate calcium and MAPK signaling,
resulting in suppression of Nfatc1 expression, which ultimately decreases
osteoclast formation and activity.
PMID- 29955676
TI - Prevalence and Factors Associated with Food Insecurity in the Context of the
Economic Crisis in Brazil.
AB - Background: The Brazilian economy has been officially in recession since 2014.
Since then, there has been an increase in the unemployment rate, cost of food,
and cuts in the budgets of social programs, among other situations that may
interfere with the food security of the population. Objectives: The aims of this
study were to identify the prevalence of and factors associated with food
insecurity (FI) in Alagoas, one of the poorest states in Brazil, and to discuss
the results in the context of the national economic crisis. Methods: This was a
cross-sectional study in a probabilistic sample of 3366 families. FI was
identified on the basis of the Brazilian Food Insecurity Measurement. The
associations with independent variables that achieved P < 0.2 (by chi-square
test) in the crude analysis were submitted to multivariable analysis. Results:
The observed prevalence of FI was 58.3% (33.1%, 17.9%, and 7.3% for mild,
moderate, and severe FI, respectively), which is considerably higher than the
34.6% found in 2013 by the Brazilian Institute of Geography and Statistics before
the worsening of the economic crisis. The factors independently associated with
FI in this study included the following: female head of household, head of the
family having no income, female head of household being overweight, >=4 family
members, <=4 rooms in the house, household income less than the minimum wage,
family belonging to the lower economic classes (D or E), using the Bolsa Familia
program, residing in a nonmasonry house, or not residing in their own house.
Conclusions: The prevalence of FI in Alagoas is very high, and considering
previous studies, there was a marked increase in FI during the Brazilian economic
crisis. All associated factors are related to the greater social vulnerability of
the family. The present data point to the need to strengthen public policies for
health promotion, education, employment, and income and to ensure the human right
to adequate food, with the aim of reducing social vulnerability within the family
in a sustainable way. In addition, this study contributes to the understanding of
how national conditions can influence household-level FI.
PMID- 29955677
TI - Long-Term Treatment of Overweight and Obesity with Polyglucosamine (PG L112):
Randomized Study Compared with Placebo in Subjects after Caloric Restriction.
AB - Background: Short-term treatment of overweight and obesity with polyglucosamine
(PG) was found to be more effective than placebo and orlistat in double-blind
clinical studies. Objective: The aim of the study was to compare the efficacy of
long-term (12-mo) treatment of weight loss with PG and placebo (PL). Methods:
This was a double-blind randomized study in 100 participants of both sexes with a
body mass index (in kg/m2) >30 to <35. One group of 50 participants was treated
for 1 y with PG at 1.6 g/d and a similar group received PL. PG is a combination
of low-molecular-weight chitosan with organic acids. Participants were instructed
to reduce their caloric intake by 10% and increase the physical activity level by
9 metabolic equivalent task hours/wk. Dietary compliance was checked every 3 mo
by using a weekly questionnaire [food intake assessment (FIA)] based on 25
different food servings. Body weight (BW), waist circumference (WC), blood
pressure (BP), glucose, lipids, and high-sensitivity C-reactive protein (hs-CRP)
were also monitored. Results: Ninety-seven participants completed the study (49
in the PG group, 48 in the PL group). The decrease in calories was similar in
both groups, as was the change in number of food servings (P > 0.05, ANOVA).
Decreases in BW and WC were 8.0 kg and 10.2 cm, respectively, in the PL group,
whereas they were 12.1 kg and 13.3 cm in the PG group (P < 0.001, ANOVA). The
decrease in BP, plasma lipids, glucose, and hs-CRP was more evident in the group
treated with PG (P < 0.05, ANOVA). The intake of lipids was found to correlate
directly with hs-CRP, with the exception of extra-virgin olive oil. Conclusions:
PG was found to be more effective than PL in reducing BW, WC, glucose, BP, plasma
lipids, and hs-CRP in moderately obese individuals undergoing a 10% caloric
reduction and a slight increase in physical activity. Dietary monitoring with the
use of an FIA was an effective tool in supporting dietary compliance. This trial
was registered at clinicaltrials.gov as U111111292405 (WHO).
PMID- 29955678
TI - Photographic Methods for Measuring Packaged Food and Beverage Products in
Supermarkets.
AB - Background: The global obesity pandemic and rates of nutrition-related
noncommunicable diseases (NCDs) have increased worldwide, especially in the Latin
American and Caribbean region. In an attempt to control this obesity epidemic,
the Chilean government has established a comprehensive set of regulatory actions,
including beverage taxation, warning labels on foods, and marketing restrictions
to children. To improve the effectiveness of actions to prevent obesity, a better
understanding of the food environment is needed. Objective: We developed and
standardized photographic methods to assess and monitor packaged food and
beverage products in supermarkets. Methods: A standardized protocol and food
categorization system was used to guide photo collection and data management of
photos taken between February and April 2015 in 11 supermarkets, consisting of 5
different supermarket chains, from high- (n = 6) and lower-middle (n = 5)-income
neighborhoods in Santiago, Chile. Photos (n = ~50,000) from nearly 10,000 unique
food products from high- and lower-middle-income neighborhoods were used for this
study. Results: We developed standardized methods to use photographs to assess
and monitor the food environment. A food categorization scheme is essential to
guiding the data collection process. Substantial time and human resources are
required to assess packaged food and beverage products in supermarkets. Because
the number of photos per food product is variable, the organization of the
photographs according to the food categorization system, before data entry, is
imperative for easy access during data entry and analysis. We identified the
information necessary for a photographic registry, which, with the food
categorization system, is critical to create unique identifiers that are linked
to each food product and its photos. Conclusions: To adequately monitor food
environments, standardized methods for food photo collection and management are
essential. The information collected on food package photos to monitor food
environments is important for guiding and evaluating actions in the context of
the ongoing obesity and NCD epidemics.
PMID- 29955679
TI - Long-Term Dose-Response Condensed Tannin Supplementation Does Not Affect Iron
Status or Bioavailability.
AB - Background: Repeated phytic acid consumption leads to iron absorption adaptation
but, to the best of our knowledge, the impact of repeated tannin consumption has
not yet been established. Salivary proline-rich proteins (PRPs) may improve iron
absorption by precipitating tannins. Objectives: This study aimed to determine
the effect of long-term, dose-response condensed tannin supplementation on iron
bioavailability and status and to assess the effect of salivary proteins on iron
bioavailability during prolonged condensed tannin consumption. A secondary
objective was to assess astringency as a potential marker for adaptation to
tannins and iron bioavailability. Methods: Eleven nonanemic women were enrolled
in a double-blind 3-dose crossover trial. Three (1.5, 0.25, or 0.03 g) condensed
tannin supplements were consumed 3 times/d for 4 wk in random order, with 2-wk
washouts in between. Meal challenges were employed before and after
supplementation to assess iron bioavailability, iron status, salivary PRP
changes, and astringency. Results: Tannin supplementation in any dose did not
change iron bioavailability at any dose (P > 0.82) from weeks 0 to 4. Hemoglobin
(P = 0.126) and serum ferritin (P = 0.83) were unchanged by tannin dose from
weeks 0 to 4. There were significant correlations among tannin supplementation
and iron bioavailability, basic proline-rich proteins (bPRPs) (r = 0.366, P =
0.003), and cystatin production (r = 0.27, P = 0.03). Astringency ratings did not
change significantly within or between tannin doses (P > 0.126), but there were
negative relations among bPRP (r < -0.32, P < 0.21), cystatin production (r <
0.2, P < 0.28), and astringency ratings. Conclusions: Condensed tannin
consumption did not affect iron bioavailability or status regardless of the
supplementation period in premenopausal nonanemic women. Correlation analyses
suggest that bPRPs and cystatins are associated with improved iron
bioavailability and that lower ratings of astringency may predict improved iron
absorption with repeated tannin consumption.
PMID- 29955680
TI - Co-construction and Evaluation of a Prevention Program for Improving the
Nutritional Quality of Food Purchases at No Additional Cost in a
Socioeconomically Disadvantaged Population.
AB - Background: Food prices influence food choices. Purchasing foods with higher
nutritional quality for their price may help improve the diet quality of
socioeconomically disadvantaged individuals. Objective: This study aimed to
describe the co-construction and evaluation of the Opticourses prevention
program, which promotes healthy eating among participants in socioeconomically
deprived situations by improving the nutritional quality of their household food
purchases with no additional cost. Methods: Individuals were recruited in poor
districts of Marseille, France. The intervention and evaluation tools and
protocols were co-constructed with 96 individuals. Then, 93 adults willing to
participate in a standardized intervention comprising 5 participative workshops
on diet and budget were enrolled. Impact on food purchases was estimated with
experimental economics: 2-d experimental food purchase intents were observed at
baseline and endline for workshop participants (WPs, n = 35) and controls (n =
23), with the use of monetary incentives to limit social-desirability bias.
Changes in food and nutrient content and energy cost (expressed in ?/2000 kcal)
of experimental purchases were assessed. Results: The co-constructed
participative workshops included playful activities around food purchase
practices and the nutritional quality, taste, and price of foods. Experimental
purchases contained a large amount of energy at baseline for both WPs and
controls (5114 and 4523 kcal ? d-1 ? person-1, respectively). For WPs only, the
mean energy content decreased between baseline and endline (-1729 kcal ? d-1 ?
person-1; P < 0.01; medium effect size: Cohen's d = 0.5), and the percentage of
energy from free sugars and from foods high in fat, sugar, and salt also
decreased (both P < 0.05 and medium effect sizes), whereas energy cost remained
unchanged. No significant changes between baseline and endline were observed for
the controls. Conclusions: After the intervention, the energy content of
participants' experimental purchases was closer to their needs, suggesting that
the workshops helped them plan and rationalize their food purchases better. The
nutritional quality of the experimental purchases increased but energy cost did
not, showing that the co-constructed Opticourses prevention program can favorably
change food purchasing behaviors of socioeconomically disadvantaged individuals
with no additional cost. This trial was registered at clinicaltrials.gov as
NCT02383875.
PMID- 29955681
TI - Association of Pasta Consumption with Diet Quality and Nutrients of Public Health
Concern in Adults: National Health and Nutrition Examination Survey 2009-2012.
AB - Background: Pasta is a commonly consumed food in the United States; however,
little is known about pasta consumption and nutrient intake and diet quality.
Objective: This study examined the association between pasta consumption and diet
quality. Methods: This was a cross-sectional data analysis of 10,697 US adults
from the NHANES 2009-2012, a nationally representative survey. The main outcome
measures were diet quality as assessed by the Healthy Eating Index-2010 (HEI
2010), nutrient intakes, and dietary patterns. Cluster analysis was used among
pasta consumers to characterize dietary patterns. Regression analyses determined
differences between groups. Results: Overall mean diet quality was similar
between pasta consumers and nonconsumers. However, consumers of "pasta, noodles"
had 5.6% higher HEI-2010 scores; HEI-2010 scores were 7.9% lower in those who ate
"macaroni and cheese." Consumers of pasta, "pasta, noodles," and "pasta mixed
dishes, excluding macaroni and cheese" ("pasta mixed dishes") had higher dietary
fiber intakes by 11.0-13.6% (range: 1.89-2.35 g/d). Consumption of "pasta mixed
dishes" was associated with a 5% increase in both potassium and sodium intakes
(~150 and 190 mg/d, respectively). Cluster analyses identified pasta-eating
patterns that are associated with both increased and decreased diet quality
compared with nonconsumers. Conclusions: Different dietary patterns exist with
regard to pasta consumption. These pasta patterns contribute in different ways to
diet quality and intakes of fiber, sodium, and potassium. Therefore, it is
critical to separate types of pasta and pasta dishes before relating to dietary
intakes.
PMID- 29955683
TI - The Nutritional Status of HIV-Infected US Adults.
AB - Background: Nutrition is critical to HIV mortality and morbidity. Improved
treatment modalities have increased life expectancy of HIV-infected individuals.
More than 1 million US adults are living with HIV, but little is known about
their nutritional status. Objective: We aimed to characterize the nutritional
status of those living with HIV with the use of the NHANES 2003-2014. Methods:
The NHANES is a nationally representative, cross-sectional survey of the US
population and includes a household interview, medical examination, and two 24-h
dietary recalls; survey weights are applied to make the data nationally
representative. HIV antibodies were ascertained initially by immunoassay and
confirmed with Western blot. NHANES 2003-2014 data were analyzed for HIV-positive
(n = 87) and HIV-negative (n = 15,868) US adults (aged 19-49 y). Body mass index
(BMI), waist circumference, dietary intakes, and nutritional biomarkers were
estimated and compared by HIV status, stratified by sex. Results: HIV-infected
men and women had higher serum protein, lower serum albumin, and lower serum
folate than did non-HIV-infected adults. HIV-positive women had significantly
higher BMI, prevalence of overweight or obesity, and waist circumference risk and
substantially lower serum 25-hydroxyvitamin D concentrations (44 compared with 65
nmol/L) than did HIV-negative women. When compared with HIV-negative women, HIV
positive women had lower intakes of some key nutrients such as fiber, vitamin E,
vitamin K, magnesium, and potassium but had higher intakes of protein and niacin.
Conclusions: The NHANES data suggest that HIV infection is associated with poorer
markers of some nutritional status indicators; however, the US population
prevalence of HIV is <0.5%. Given the small sample size, not only in this study
but also in the United States, much more targeted research is needed to better
understand the multitude of factors that influence the nutritional status among
those living with HIV in the United States, especially among women.
PMID- 29955682
TI - The Nutrient and Metabolite Profile of 3 Complementary Legume Foods with
Potential to Improve Gut Health in Rural Malawian Children.
AB - Background: Environmental enteric dysfunction (EED), frequently seen in rural
Malawian children, causes chronic inflammation and increases the risk of
stunting. Legumes may be beneficial for improving nutrition and reducing the risk
of developing EED in weaning children. Objective: The objectives of this study
were to determine the nutritional value, verify the food safety, and identify
metabolite profiles of 3 legume-based complementary foods: common bean (CB),
cowpea (CP), and traditional corn-soy blend (CSB). Methods: Foods were prepared
by using local ingredients and analyzed for nutrient composition with the use of
Association of Official Analytical Chemists (AOAC) standards (950.46, 991.43,
992.15, 996.06, and 991.36) for macro- and micronutrient proximate analysis. Food
safety analysis was conducted in accordance with the Environmental Protection
Agency (7471B) and AOAC (2008.02) standards. The metabolite composition of foods
was determined with nontargeted ultra-performance LC-tandem mass spectrometry
metabolomics. Results: All foods provided similar energy; CB and CP foods
contained higher protein and dietary fiber contents than did the CSB food. Iron
and zinc were highest in the CSB and CP foods, whereas CB and CP foods contained
higher amounts of magnesium, phosphorus, and potassium. A total of 652 distinct
metabolites were identified across the 3 foods, and 23, 14, and 36 metabolites
were specific to the CSB, CB, and CP foods, respectively. Among the potential
dietary biomarkers of intake to distinguish legume foods were pipecolic acid and
oleanolic acid for CB; arabinose and serotonin for CSB; and quercetin and alpha-
and gamma-tocopherol acid for CP. No heavy metals were detected, and aflatoxin
was measured only in the CSB (5.2 parts per billion). Conclusions: Legumes in the
diet provide a rich source of protein, dietary fiber, essential micronutrients,
and phytochemicals that may reduce EED. These food metabolite analyses identified
potential dietary biomarkers of legume intake for stool, urine, and blood
detection that can be used in future studies to assess the relation between the
distinct legumes consumed and health outcomes. This trial was registered at
clinicaltrials.gov as NCT02472262 and NCT02472301.
PMID- 29955685
TI - Assessment of the Nutrition Care Process in US Hospitals Using a Web-Based Tool
Demonstrates the Need for Quality Improvement in Malnutrition Diagnosis and
Discharge Care.
AB - Background: Malnutrition in hospitalized patients is a pervasive problem in the
United States. To our knowledge, although malnutrition has been acknowledged as a
concern for >40 y, it has not yet been well addressed with a systematic, process
improvement approach. Objectives: We aimed to characterize the current nutrition
care process in US hospitals to establish a baseline for improvements. We also
aimed to demonstrate the application of a web-based quality improvement tool as a
simple approach to address malnutrition in hospitalized patients. Methods: We
established a web-based tool to measure and assess nutrition care practices from
hospital electronic medical records. Individual institutions self-selected to
participate and were assigned a unique identifier to input data. Aggregated
patient data from registered institutions were assessed. Data from all
institutions were combined and are presented as the totals for each variable.
Results: Of 243 registered users, 97 provided data and 150 reports were included
in the analysis, resulting in a total of 107,106 patients. Almost all patients
(89.98%) were screened for malnutrition risk within 24 h of admission, and ~30%
were at risk for malnutrition. Of those at risk, ~65% received a registered
dietitian nutritionist consultation or an order for an oral nutrition supplement.
The rate of malnutrition diagnosis for those at risk was ~14%, and <10% of
patients received a recommendation or prescription for an oral nutrition
supplement at discharge. Conclusions: Malnutrition remains an issue for
hospitalized patients, particularly the gap between those screened as at risk and
those diagnosed with malnutrition. Moreover, discharge recommendations for
patients who are screened as at risk for malnutrition are also lacking. These
data demonstrate that a web-based quality improvement tool could be used to
capture the nutrition care practice at an institution level to provide directed
approaches for addressing hospital malnutrition and improving care of patients at
risk for malnutrition.
PMID- 29955686
TI - For Low-Income Americans, Living <=1 Mile (<=1.6 km) from the Nearest Supermarket
Is Not Associated with Self-Reported Household Food Security.
AB - Background: Motivated by concern over lack of access to nutritious food in low
income neighborhoods, healthy food financing initiatives have encouraged the
introduction of new supermarkets. Extensive research on the association between
the food retail environment and nutrition outcomes has shown mixed results. There
has been less research specifically on food security outcomes. Objective: We
assessed the association between multiple food environment measures and food
security for low-income US households. Methods: By using the USDA's nationally
representative 2012-2013 Food Acquisition and Purchase Survey (FoodAPS; n = 4826
households), which provides unique information about neighborhood- and household
level food retailer access, we quantified cross-sectional associations between
food environment characteristics and household-level outcomes, with and without
regression controls. Logistic regression analysis was used for binary household
food security outcomes. Results: Most households bypassed the nearest retailer to
select a primary retailer farther from home. For low-income households, distance
to the nearest supermarket and to the primary retailer was not associated with
food security. In comparison to shopping with households' own automobile, the
odds of being food secure were lower for households that used another automobile
(OR: 0.59; 95% CI: 0.38, 0.90) or other transportation (OR: 0.32; 95% CI: 0.17,
0.61) to reach the primary retailer. Conclusions: Having a closest supermarket
<=1 mile from home was not associated with household food security. In contrast,
the mode of transportation used to access the primary retailer was associated
with household food security. In future research, it may be valuable to not only
focus on the distance to the nearest supermarket but to investigate the qualities
of the food retail environment at distances >1 mile that are most strongly
associated with food security outcomes.
PMID- 29955684
TI - The Relation between Polyphenols and Body Composition in US Hispanics/Latinos:
Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Study of Latinos Nutrition and Physical Activity Assessment Study (SOLNAS).
AB - Background: Polyphenols offer high antioxidant potential that may protect against
chronic diseases. Epidemiologic evidence documenting their influence on body
composition and obesity risk is limited, particularly among Hispanics/Latinos who
are disproportionately prone to obesity. Objectives: The aims of this study were
to evaluate cross-sectional associations of urinary polyphenols with body mass
index (BMI) and body fat percentage (%BF) in a diverse Hispanic/Latino population
and to assess the reliability of polyphenol measurements. Methods: Participants
were 442 adults from the Study of Latinos/Nutrition and Physical Activity
Assessment Study (SOLNAS) aged 18-74 y. Doubly labeled water was used as an
objective recovery biomarker of energy. Polyphenol excretion from 24-h urine
samples was assessed. Measures were repeated in a subsample (n = 90) to provide a
reliability measure. Anthropometric measures were obtained by trained personnel,
and %BF was measured by 18O dilution. Linear regression models were used to
evaluate multivariable associations between body composition and polyphenols.
Spearman correlation coefficients between BMI and %BF with polyphenols and
intraclass correlation coefficients (ICCs) between polyphenol measures were
computed. Results: A weak correlation was observed for resveratrol and %BF (r =
0.11, P = 0.02). In multivariable-adjusted regression models, weak inverse
associations were observed for resveratrol and urolithin A with %BF [beta +/- SE:
-0.010 +/- 0.004 (P = 0.007) and -0.004 +/- 0.002 (P = 0.03), respectively]. For
every 50% increase in these urinary polyphenols, there was a 1% and 0.4% decrease
in %BF. Urolithin A was inversely associated with BMI (beta +/- SE: -0.004 +/-
0.002; P = 0.02) and with 5% lower odds of obesity in models not adjusted for
total energy expenditure (TEE; OR: 0.95; 95% CI: 0.91, 0.99; P = 0.02). For every
50% increase in urolithin A, there was a 0.4-unit decrease in BMI. Associations
were attenuated after adjustment for TEE. Reliability study findings were
indicative of weak to moderate correlations (ICCs: 0.11-0.65), representing a
degree of within-person variation in polyphenol biomarkers. Conclusions: Although
associations were weak, resveratrol and urolithin A were inversely associated
with obesity. Repeated polyphenol urine measures could clarify their long-term
impact on body adiposity.
PMID- 29955687
TI - Enriching the Starter Diet in n-3 Polyunsaturated Fatty Acids Reduces Adipocyte
Size in Broiler Chicks.
AB - Epidemiologic studies associate perinatal intake of eicosapentaenoic acid (EPA,
20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) with reduced adiposity in
children, suggesting that these fatty acids may alter adipose tissue development.
The objective of this study was to determine whether enriching the perinatal diet
in EPA and DHA reduces fat deposition in young chicks. Cobb 500 broiler chicks
were fed isocaloric diets containing fat (8% wt:wt) from fish oil (FO), lard,
canola oil, or flaxseed oil from 7 to 30 d of age. Adiposity (abdominal fat pad
weight/body weight) at 30 d was not significantly affected by diet, but FO
significantly reduced adipocyte size, increasing the abundance of small
adipocytes. Plasma nonesterified fatty acid concentrations suggest that reduced
adipocyte size was due, in part, to enhanced mobilization of fatty acids from
adipose tissue. Our work indicates that dietary EPA and DHA effectively reduce
the size of developing adipocytes in juveniles, which may limit adipose
deposition and provide metabolic benefits.
PMID- 29955688
TI - Skeletal Muscle Acute and Chronic Metabolic Response to Essential Amino Acid
Supplementation in Hypertriglyceridemic Older Adults.
AB - Background: Supplementation with essential amino acids (EAAs) + arginine is a
promising nutritional approach to decrease plasma triglyceride (TG)
concentrations, which are an independent risk factor for ischemic heart disease.
Objective: The objective of this study was to examine the effects of 8 wk of EAA
supplementation on skeletal muscle basal metabolite concentrations and changes in
metabolic response to acute EAA intake, with an emphasis on mitochondrial
metabolism, in adults with elevated TGs to better understand the mechanisms of
lowering plasma TGs. Methods: Older adults with elevated plasma TG concentrations
were given 22 g EAAs to ingest acutely before and after an 8-wk EAA
supplementation period. Skeletal muscle biopsy samples were collected before and
after acute EAA intake, both pre- and postsupplementation (4 biopsy samples), and
targeted metabolomic analyses of organic acids and acylcarnitines were conducted
on the specimens. Results: Acute EAA intake resulted in increased skeletal muscle
acylcarnitine concentrations associated with oxidative catabolism of the
supplement components, with the largest increases found in acylcarnitines of
branched-chain amino acid oxidative catabolism, including isovaleryl-carnitine
(2200%) and 2-methylbutyryl-carnitine (2400%). The chronic EAA supplementation
resulted in a 19% decrease in plasma TGs along with accumulation of long-chain
acylcarnitines myristoyl- (90%) and stearoyl- (120%) carnitine in skeletal muscle
and increases in succinyl-carnitine (250%) and the late-stage tricarboxylic acid
cycle intermediates fumarate (44%) and malate (110%). Conclusions:
Supplementation with EAAs shows promise as an approach for moderate reduction in
plasma TGs. Changes in skeletal muscle metabolites suggest incomplete fatty acid
oxidation and increased anaplerosis, which suggests a potential bottleneck in
fatty acid metabolism.
PMID- 29955689
TI - The Impact of Policies to Reduce trans Fat Consumption: A Systematic Review of
the Evidence.
AB - Background: The consumption of industrially produced trans fatty acids (TFAs) has
been associated with an increased risk of heart disease. In recognition of this,
countries, states, and cities worldwide have implemented TFA policies aimed at
reducing their availability in the food supply. Objective: This article aims to
provide an update of the evidence of the effectiveness of policies aimed at
reducing TFAs in the food supply. Methods: A systematic review of the literature
from 2013 onward was conducted, building on a previously published review that
examined the evidence of the impact of TFA policies worldwide from 2000 to 2012.
Studies that were 1) empirical, 2) examined a TFA policy, and 3) examined the
effect of the policy on TFA amounts and availability pre- and post-policy
intervention were included. Modeling studies examining the impact of TFA policies
on cardiovascular, equity, and economic outcomes were also included. Results: A
total of 18 articles from the updated search were combined with 14 articles from
the previous review (total = 32 articles). All types of TFA policies led to their
reduction; however, trans fat bans had a larger impact (TFAs virtually
eliminated) than did voluntary (range: 20-38% reduction in TFA intakes) or
labeling (range: 30-74% reduction in TFA intakes, plasma serum, or breast-milk
concentrations) approaches to reducing TFA amounts in the food supply. Product
reformulation to reduce TFAs had variable effects on saturated fatty acid (SFA)
contents in these foods; however, the combined amount of TFAs and SFAs declined
in most products. Overall, the modeling studies indicated that TFA bans would
reduce heart disease risk, benefit socioeconomically disadvantaged populations
the most, and be cost-saving. Conclusions: Policies aimed at reducing TFAs in the
food supply are effective and will likely reduce the burden of diet-related
disease, particularly among the most vulnerable socioeconomic groups. Although
all policy approaches lead to reductions in TFAs in foods, TFA bans are likely
the most effective, economical, and equitable policy approach to reducing TFAs in
the food supply.
PMID- 29955691
TI - Development of a Dichotomous Indicator for Population-Level Assessment of Dietary
Diversity in Women of Reproductive Age.
AB - Background: Dietary diversity is a key element of diet quality, but diets of
women of reproductive age (WRA; aged 15-49 y) in resource-poor settings are often
deficient in a range of micronutrients. Previous work showed associations between
simple food-group diversity indicators (FGIs) and micronutrient adequacy among
WRA. For operational and advocacy purposes, however, there is strong demand for a
dichotomous indicator reflecting an acceptable level of dietary diversity.
Objective: The aim of the study was to develop a dichotomous indicator of dietary
diversity in WRA. Methods: We performed a secondary analysis of 9 data sets
containing quantitative dietary data from WRA in resource-poor settings (total n
= 4166). From the raw dietary data, we calculated an individual "mean probability
of adequacy" (MPA) across 11 micronutrients. Several candidate FGIs were
constructed. Indicator performance in predicting an MPA >0.60 was assessed within
each data set by using receiver-operating characteristic analysis and sensitivity
and specificity analysis at various FGI cutoffs. The analysis was performed
separately for nonpregnant and nonlactating (NPNL) women and for lactating women.
Results: We identified 2 "best candidate" dichotomous indicators on the basis of
9- or 10-point food-group scores (FGI-9 and FGI-10) with a cutoff of >=5 food
groups. Both were significantly correlated to MPA in each site (P < 0.001). Areas
under the curve were moderate, ranging from 0.62 to 0.82 among NPNL women and
from 0.56 to 0.90 among lactating women. Comparisons of results slightly favored
FGI-10 for all women. Conclusions: When resource-intensive dietary methods are
not feasible, a simple dichotomous indicator based on a cutoff of >=5 of 10
defined food groups reflects "minimum dietary diversity for women of reproductive
age." According to the conclusions of a consensus meeting of experts, this
indicator is well suited for population-level assessment, advocacy, and possibly
also for tracking of change in dietary diversity across time.
PMID- 29955690
TI - Healthy Dietary Patterns for Preventing Cardiometabolic Disease: The Role of
Plant-Based Foods and Animal Products.
AB - Diets rich in plant foods are increasingly recommended to lower the risk of
cardiometabolic diseases because of strong evidence that fruit, vegetables,
legumes, whole grains, nuts, and seeds are protective. Although some animal
products, such as unprocessed lean red meat, poultry, eggs, and dairy products,
are recommended in dietary patterns to prevent cardiometabolic diseases, many
health professionals advocate for exclusively plant-based dietary patterns. The
aim of this article was to review recent evidence on the relative contributions
of plant-based foods and animal products to a healthy dietary pattern. Secondary
aims were to discuss current consumption patterns and adherence to dietary
recommendations. Epidemiologic evidence suggests that a higher intake of plant
based foods is associated with a lower risk of cardiometabolic disease, whereas a
higher meat intake increases the risk of cardiometabolic disease and the
replacement of small quantities of animal protein with plant protein is
associated with lower risk. Randomized controlled studies show that nutrient
dense diets containing animal protein, including some unprocessed lean meats,
improve cardiovascular disease risk factors. Therefore, it is likely that the
consumption of animal products, at recommended amounts, in the context of a
dietary pattern that meets recommendations for fruit, vegetables, whole grains,
nuts, seeds, and legumes, and does not exceed recommendations for added sugar,
sodium, and saturated fat, may not increase cardiometabolic risk. Currently,
adherence to these recommendations is suboptimal. Therefore, rather than debating
the merits of healthy dietary patterns that are exclusively plant-based or that
include animal sources in recommended amounts, the focus should be on improving
overall eating patterns to align with dietary guidelines. Registered
Dietitian/Nutritionists (RDNs) have the requisite nutrition expertise to
facilitate change at the individual and population levels to promote adherence to
healthy dietary patterns. Importantly, advocacy activities are urgently needed to
create a healthier food environment, and all health professionals, including
RDNs, must play a role.
PMID- 29955692
TI - Examination of Protein Quantity and Protein Distribution across the Day on Ad
Libitum Carbohydrate and Fat Intake in Overweight Women.
AB - Background: The effects of meal-specific protein quantity and protein
distribution throughout the day on daily food intake are relatively unknown.
Objectives: The aims were to test 1) whether the consumption of higher-protein
(HP) compared with normal-protein (NP) meals consumed at each eating occasion
reduce free-living, daily carbohydrate and fat intakes in overweight women during
energy balance conditions and 2) whether the distribution of protein consumed
throughout the day affects food intake outcomes. Methods: Seventeen women [mean
+/- SEM age: 33 +/- 1 y; body mass index (in kg/m2): 27.8 +/- 0.1] completed the
following tightly controlled, crossover design study. Participants were provided
with and randomly consumed three 6-d eucaloric diets containing NP or HP (15% or
25% of energy as protein, respectively). The protein content within the NP diet
used an even distribution pattern (EVEN; 21 +/- 1 g protein/meal) throughout the
day, whereas the protein contents within the HP diets used either EVEN (35 +/- 1
g protein/meal) or an uneven distribution pattern (UNEVEN; 19 +/- 1 g
protein/breakfast, 26 +/- 1 g protein/lunch, 63 g protein/dinner). On day 7 of
each diet, the participants were asked to consume the diet-specific absolute
protein quantity (in grams) at each eating occasion but were provided with a
surplus of carbohydrate- and fat-rich foods to consume, ad libitum, during each
eating occasion. Results: Eating more protein (HP compared with NP) or evenly
distributing protein throughout the day (HP-EVEN compared with HP-UNEVEN) did not
reduce the consumption of ad libitum fat- and carbohydrate-rich foods throughout
the day (NP-EVEN: 2850 +/- 240 kcal/d; HP-EVEN: 2910 +/- 240 kcal/d; HP-UNEVEN:
3160 +/- 200 kcal/d). Despite the lack of differences in daily energy intake, the
breakfast meal within the HP-EVEN diet led to lower ad libitum carbohydrate and
fat intakes than the breakfast meals in the NP-EVEN and HP-UNEVEN diet conditions
(P < 0.05). Conclusion: Providing 30 g protein/meal at each eating occasion
throughout the day did not influence free-living, daily intake of highly
palatable, carbohydrate- and fat-rich foods in overweight women. This trial was
registered at clinicaltrials.gov as NCT02614729.
PMID- 29955693
TI - The Impact of Tannin Consumption on Iron Bioavailability and Status: A Narrative
Review.
AB - Iron deficiency remains a global health issue, and antinutritional factors, such
as tannins, are often cited as contributors to the high prevalence of deficiency.
Despite this, tannin-rich diets may have potential beneficial cardiovascular and
cancer-fighting properties because of the antioxidant activity of tannins.
Furthermore, epidemiologic studies and long-term trials involving participants
who consumed diets rich in antinutritional factors, particularly tannins,
conflict with single-meal bioavailability studies. The purpose of this narrative
review is to determine the effect of tannins on iron bioavailability and status
and establish whether adaptation to tannins reduces the antinutritional effects
of tannins over time. We also aimed to compare tannins used in iron studies.
Common themes related to iron bioavailability and iron status with tannin
consumption were collected and collated for summary and synthesis based on models
and subjects used. Overall, there was dissonance between iron bioavailability and
status in studies. Single-meal studies with hydrolyzable and oligomeric catechin
and epicatechin tannins (tea and tannic acid) generally support reductions in
bioavailability related to tannin consumption but not consumption of condensed
tannin, which are more commonly found in food. Long-term animal model,
epidemiologic, and multimeal studies generally do not support changes in iron
status related to tannin intake. Studies suggest that long-term tannin
consumption may impact iron status in a different manner than single-meal studies
or bioavailability iron models predict. Furthermore, iron bioavailability studies
that use condensed tannins, which are more commonly consumed, may better predict
mealtime iron bioavailability. More research is needed to develop representative
antinutritional iron studies and investigate mechanisms underlying the adaptation
to tannins and other antinutritional factors that occur over time.
PMID- 29955694
TI - Indexes for Assessing Adherence to a Mediterranean Diet from Data Measured
through Brief Questionnaires: Issues Raised from the Analysis of a Greek
Population Study.
AB - Background: Adherence to a Mediterranean diet (MD) has been quantified through
various indexes that rely on full-length questionnaires, but their application in
data collected with brief questionnaires has not been systematically
investigated. Objective: We aimed to evaluate the ability of the commonly used MD
score (MDS) to classify individuals according to their adherence to an MD when
applied to data collected with brief questionnaires. Methods: We assessed the
diet of 200 participants from a Greek national health survey with the use of 2
instruments: 1) a validated, detailed food-frequency questionnaire (FFQ)
estimating grams per day of intake of individual foods and 2) a selection of 19
questions from the Baseline Nutrition Credits4Health (BNC4H) electronic platform
questionnaire that assessed servings with subjective serving sizes. We calculated
the MDS_FFQ (referent) and MDS_BNC4H indexes from each questionnaire and
estimated their correlation and the percentage of study participants who were
ranked in an identical tertile in both indexes. We repeated the analyses for 2
additional indexes defined with criteria different from the MDS [Mediterranean
Diet Index (MDI)_BNC4H and Mediterranean Diet Assessment Score (MEDAS)_ BNC4H].
Results: Spearman correlation coefficients for the MDS_FFQ were 0.31 with the
MDS_BNC4H, 0.24 with the MDI_BNC4H, and 0.23 with the MEDAS_BNC4H. The proportion
of participants ranked into the same adherence level as the referent MDS_FFQ was
50% for the MDS_BNC4H (weighted kappa = 0.27) and lower for the other indexes.
The use of medians as cutoffs (as in the MDS_FFQ) had low discriminative ability
when applied to servings per day (MDS_BNC4H) in some MDS components, leading to
comparability problems in the range of values between the 2 indexes. Conclusions:
Our findings highlight certain issues that need to be considered when applying
pre-existing MD indexes in settings with different dietary assessments. Given the
widespread use of electronic platforms for dietary assessment, our results may
offer further insight into designing brief, simplified questionnaires that aim to
estimate MD adherence with easily quantifiable scores.
PMID- 29955695
TI - Decreased Appetite after High-Intensity Exercise Correlates with Increased Plasma
Interleukin-6 in Normal-Weight and Overweight/Obese Boys.
AB - Background: High-intensity exercise (HIEX) suppresses appetite in adults and is
thought to be mediated by appetite-regulating hormones. However, the effects of
HIEX-induced inflammatory and stress biomarkers on appetite control and body
weight have not been reported in children or adults. Objective: The objective of
this study was to describe the effects of acute HIEX at 70% peak oxygen
consumption (VO2peak) on postexercise appetite and selective biomarkers of
inflammation, stress, and appetite regulatory hormones in normal-weight (NW) and
in overweight/obese boys. Methods: NW (n = 11) and overweight/obese (n = 11) boys
aged 10-18 y were randomly assigned in a crossover design to either rest or HIEX.
Visual analog scale appetite ratings and plasma biomarkers of appetite,
inflammation, stress, and glucose control were measured after HIEX or rest.
Results: Appetite increased from baseline to 110 min (P < 0.001), but was lower
after HIEX (P = 0.04), with no difference between body weight groups. HIEX also
resulted in lower active ghrelin (P < 0.001) and increased interleukin-6 (IL-6; P
< 0.001), tumor necrosis factor-alpha (P < 0.001), and cortisol (P < 0.001)
concentrations, independent of body weight. It increased blood glucose (P =
0.002) and insulin (P = 0.028) concentrations in NW but not overweight and obese
boys. Leptin, glucagon-like peptide 1, peptide tyrosine tyrosine, C-reactive
protein, and cortisol were not affected by HIEX. An inverse correlation was found
between IL-6 and appetite (r = -0.379; P = 0.012), but not any other biomarkers.
Conclusions: HIEX resulted in reduced appetite that correlated with an increase
in IL-6 in both NW and overweight/obese boys. However, although a role for IL-6
in the response can be suggested, the suppression of appetite was potentially
mediated by the decrease in active ghrelin and/or increase in cortisol. This
trial was registered at clinicaltrials.gov as NCT02619461.
PMID- 29955696
TI - Usual Consumption of Specific Dairy Foods Is Associated with Breast Cancer in the
Roswell Park Cancer Institute Data Bank and BioRepository.
AB - Background: Dairy foods are complex mixtures which include nutrients and non
nutrient substances that could potentially influence cancer etiology, including
breast cancer. Objective: The purpose of this study was to examine associations
between the types and quantity of dairy foods consumed and the risk of breast
cancer among women participating in the Roswell Park Cancer Institute Data Bank
and BioRepository (DBBR) between 2003 and 2014. Methods: Archived clinical and
questionnaire data were obtained from the DBBR from 1941 women diagnosed with
breast cancer between December 2003 and October 2014, and 1237 control
participants. Intakes of dairy foods were queried with a self-administered food
frequency questionnaire and grouped into monthly intakes of total dairy, milk,
yogurt, low-fat cheese, other cheese, and sweet dairy. ORs and 95% CIs were
estimated with unconditional logistic regression adjusting for age, race, body
mass index, menopausal status, energy intake, type of milk usually consumed,
cigarette smoking status, and family history of breast cancer. Results: Total
dairy intakes were associated with a non-significant 15% reduction in breast
cancer risk (P = 0.11). Higher intakes of yogurt were associated with reduced
risk of breast cancer (OR: 0.61; 95% CI: 0.46, 0.82) and higher intakes of
American, cheddar, and cream cheeses were associated with a marginally
significant increased risk (OR: 1.53; 95% CI: 0.99, 2.34; P = 0.05). Associations
with dairy foods were mixed when stratified by estrogen receptor (ER) status, and
in general reflected those of overall breast cancer. However, we observed
positive associations between milk intake and risk of ER- breast cancer (OR:
1.58; 95% CI: 1.05, 2.37) and inverse associations between sweet dairy and ER+
breast cancer (OR: 0.52; 95% CI: 0.29, 0.95). Conclusions: Specific dairy foods
may contribute to breast cancer risk in women, although the risk varies by source
of dairy. Future studies are warranted to confirm the protective potential of
yogurt in this type of cancer.
PMID- 29955697
TI - Realistic Test-Meal Protocols Lead to Blunted Postprandial Lipemia but Similar
Inflammatory Responses Compared with a Standard High-Fat Meal.
AB - Background: A substantial increase in triglycerides (TGs) after a meal is
associated with an increased risk of cardiovascular disease. Most studies
investigating the effects of a meal on TGs have not used meals that reflect
typical consumption. Objective: The objective of this study was to compare the TG
and inflammatory responses of true-to-life meals, containing moderate fat and
energy contents, with a high-fat, high-energy, low-carbohydrate meal (HFM)
typically used to test TG responses. Methods: Nine healthy, insufficiently active
men [mean +/- SD age: 25.1 +/- 6.7 y; body mass index (in kg/m2): 25.8 +/- 7.0;
<150 min moderate- to vigorous-intensity physical activity/wk] completed 3 meal
trials in random order: an HFM (17 kcal/kg, 60% fat), a moderate-fat meal (MFM;
8.5 kcal/kg, 30% fat), and a biphasic meal (BPM), in which participants consumed
the full MFM at baseline and 3 h postmeal. Blood samples were collected via an
indwelling catheter at baseline and hourly for 6 h. Results: Peak blood TGs were
significantly greater (P = 0.003) after the HFM (285.2 +/- 169.7 mg/dL) than
after the MFM (156.0 +/- 98.7 mg/dL), but the BPM (198.3 +/- 182.8 mg/dL) was not
significantly different from the HFM (P = 0.06) or the MFM (P = 0.99). Total area
under the curve for TGs was greater after the HFM (1348.8 +/- 783.7 mg/dL * 6 h)
than after the MFM (765.8 +/- 486.8 mg/dL * 6 h; P = 0.0005) and the BPM (951.8
+/- 787.7 mg/dL * 6 h; P = 0.03), although the MFM and BPM were not significantly
different (P = 0.72). There was a significant time-by-meal interaction for
interferon gamma, but not for interleukins 6, 8, or 10. Conclusion: These
findings in insufficiently active, healthy young men suggest that the large TG
response after HFMs in previous studies may not reflect the metabolic state of
many individuals in daily life.
PMID- 29955698
TI - Tricaprylin Alone Increases Plasma Ketone Response More Than Coconut Oil or Other
Medium-Chain Triglycerides: An Acute Crossover Study in Healthy Adults.
AB - Background: Ketones are the brain's main alternative fuel to glucose. Dietary
medium-chain triglyceride (MCT) supplements increase plasma ketones, but their
ketogenic efficacy relative to coconut oil (CO) is not clear. Objective: The aim
was to compare the acute ketogenic effects of the following test oils in healthy
adults: coconut oil [CO; 3% tricaprylin (C8), 5% tricaprin (C10)], classical MCT
oil (C8-C10; 55% C8, 35% C10), C8 (>95% C8), C10 (>95% C10), or CO mixed 50:50
with C8-C10 or C8. Methods: In a crossover design, 9 participants with mean +/-
SD ages 34 +/- 12 y received two 20-mL doses of the test oils prepared as an
emulsion in 250 mL lactose-free skim milk. During the control (CTL) test,
participants received only the milk vehicle. The first test dose was taken with
breakfast and the second was taken at noon but without lunch. Blood was sampled
every 30 min over 8 h for plasma acetoacetate and beta-hydroxybutyrate (beta-HB)
analysis. Results: C8 was the most ketogenic test oil with a day-long mean +/-
SEM of +295 +/- 155 umol/L above the CTL. C8 alone induced the highest plasma
ketones expressed as the areas under the curve (AUCs) for 0-4 and 4-8 h (780 +/-
426 umol ? h/L and 1876 +/- 772 umol ? h/L, respectively); these values were 813%
and 870% higher than CTL values (P < 0.01). CO plasma ketones peaked at +200
umol/L, or 25% of the C8 ketone peak. The acetoacetate-to-beta-HB ratio increased
56% more after CO than after C8 after both doses. Conclusions: In healthy adults,
C8 alone had the highest net ketogenic effect over 8 h, but induced only half the
increase in the acetoacetate-to-beta-HB ratio compared with CO. Optimizing the
type of MCT may help in developing ketogenic supplements designed to counteract
deteriorating brain glucose uptake associated with aging. This trial was
registered at clinicaltrials.gov as NCT 02679222.
PMID- 29955699
TI - Animal-Protein Intake Is Associated with Insulin Resistance in Adventist Health
Study 2 (AHS-2) Calibration Substudy Participants: A Cross-Sectional Analysis.
AB - Background: High intakes of total and animal protein are associated with the risk
of type 2 diabetes (T2D). The influence of protein type on insulin resistance, a
key precursor of T2D, has not been extensively studied. Objective: The aim of
this study was to determine the associations between dietary total, animal, and
plant protein intakes as well as the animal-to-plant protein (AP) intake ratio
with insulin resistance in middle-aged and older adults. Methods: This was a
cross-sectional analysis in 548 participants (mean +/- SD age: 66.2 +/- 13.7 y)
from the calibration substudy of the AHS-2 (Adventist Health Study 2) cohort.
Participants consumed diets with a low AP intake ratio. Dietary intakes of total
and particular types of protein were calculated from six 24-h dietary recalls.
Participants completed a self-administered questionnaire on demographic,
lifestyle, health, diet intake, and physical activity characteristics.
Anthropometric variables including weight, height, and waist circumference were
measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was
calculated by using fasting serum glucose and insulin. Multiple linear regression
models were used to test the relations between total and specific protein intakes
with insulin resistance. Results: The ranges of dietary intakes of animal and
plant protein and the AP intake ratio were 0.4-87.4 and 14.0-79.2 g/d and 0.02
4.43, respectively. Dietary intakes per 10-g/d increments of total protein (beta:
0.11; 95% CI: 0.02, 0.21) and animal protein (beta: 0.11; 95% CI: 0.01, 0.20) and
the AP intake ratio (beta: 1.82; 95% CI: 0.80, 2.84) were positively related to
HOMA-IR. Plant protein was not significantly related to insulin resistance.
Conclusion: Total and animal protein intakes and the AP intake ratio were
positively associated with HOMA-IR in adults with relatively a low intake of
animal protein and a high consumption of plant protein.
PMID- 29955700
TI - The MFFAPP Tanzania Efficacy Study Protocol: Newly Formulated, Extruded,
Fortified Blended Foods for Food Aid.
AB - Fortified blended foods (FBFs) are micronutrient-fortified blends of milled
cereals and pulses that represent the most commonly distributed micronutrient
fortified food aid. FBFs have been criticized due to lack of efficacy in treating
undernutrition, and it has also been suggested that alternative commodities, such
as sorghum and cowpea, be investigated instead of corn and soybean. The
Micronutrient Fortified Food Aid Pilot Project (MFFAPP) Tanzania efficacy study
was the culmination of economic, processing, sensory, and nutrition FBF research
and development. MFFAPP Tanzania was a 20-wk, partially randomized cluster design
conducted between February and July 2016 that enrolled children aged 6-53 mo in
the Mara region of Tanzania with weight-for-height z scores >-3 and hemoglobin
concentrations <10.3 mg/dL. The intervention was complementary feeding of newly
formulated, extruded FBFs (white sorghum cowpea variety 1, white sorghum-cowpea
variety 2, red sorghum-cowpea, white sorghum-soy blend, and corn-soy blend 14)
compared with Corn Soy Blend Plus (CSB+), a current US Agency for International
Development-distributed corn-soy blend, and a no-FBF-receiving control. Screened
participants (n = 2050) were stratified by age group (6-23 and 24-53 mo) and
allocated to 1 of 7 FBF clusters provided biweekly. Biochemical and
anthropometric data were measured every 10 wk at weeks 0, 10, and 20. The primary
objectives of this study were to determine whether newly formulated, extruded
corn-, soy-, sorghum-, and cowpea-based FBFs result in equivalent vitamin A or
iron outcomes compared with CSB+. Changes in anthropometric outcomes were also
examined. Results from the MFFAPP Tanzania Efficacy Study will inform food aid
producers and distributers about whether extruded sorghum- and cowpea-based FBFs
are viable options for improving the health of the undernourished. This trial was
registered at clinicaltrials.gov as NCT02847962.
PMID- 29955701
TI - Diabetes-Specific Food Insecurity Is Associated with Impaired Heart Rate
Variability Independent of Glycemic Control: Exploratory Findings among Latinos
with Type 2 Diabetes.
AB - Background: Food insecurity (FI), diabetes prevalence, and poor diabetes outcomes
all disproportionately affect Latinos in the United States. Heart rate
variability (HRV) reflects autonomic tone, is associated with glycemic control,
and predicts mortality in type 2 diabetes. It is unknown whether FI is related to
HRV and, if so, whether glycemic control accounts for this association.
Objective: This exploratory cross-sectional study examined FI and HRV among US
Latinos with type 2 diabetes. Methods: Participants reported demographic
characteristics, socioeconomic status, and FI, including the 6-item USDA food
security module and a 1-item measure of diabetes-specific food security.
Participants wore an ambulatory electrocardiogram monitor for 24 h. In the time
domain, HRV was assessed with the SD of the R-R interval (SDNN). In the frequency
domain, the power spectrum was integrated over 3 frequency bands-very low
frequency (VLF), low frequency (LF), and high frequency (HF)-and then natural log
transformed. Unadjusted ANOVA and ANCOVA adjusted for age, sex, glycated
hemoglobin (HbA1c), and indicators of socioeconomic status compared food security
groups on HRV. Results: Participants' mean +/- SD age was 59.7 +/- 10.9 y, and
73% were women. Of the 94 participants, 63 reported FI according to the USDA food
security module and 46 reported FI according to the diabetes-specific measure.
Mean +/- SD HbA1c was 8.6% +/- 1.7% and was marginally higher among those
reporting diabetes-specific FI than those reporting diabetes-specific food
security. Participants who reported diabetes-specific FI had lower SDNN, VLF, LF,
and HF HRV with effect sizes in the small-to-medium range. Differences remained
significant even after controlling for age, sex, socioeconomic hardship, and
HbA1c. The 6-item USDA food security module was not associated with HRV.
Conclusions: Diabetes-specific FI may be a unique risk factor for poor health
outcomes among US Latinos. Efforts to address FI could benefit diabetes outcomes.
PMID- 29955702
TI - Dietary Patterns Derived by Reduced Rank Regression Are Inversely Associated with
Type 2 Diabetes Risk across 5 Ethnic Groups in the Multiethnic Cohort.
AB - Background: Reduced rank regression (RRR) is an approach to identify dietary
patterns associated with biochemical markers and risk of type 2 diabetes (T2D).
Objective: We aimed to derive dietary patterns associated with adiponectin,
leptin, C-reactive protein (CRP), and triglycerides (TGs) and to examine the
prospective associations of these patterns with T2D risk in 5 ethnic/racial
groups with differences in T2D rates. Methods: The Multiethnic Cohort (MEC)
included 215,831 African-American, Japanese-American, Latino, Native Hawaiian,
and white adults living in Hawaii and California who completed a validated
quantitative food-frequency questionnaire in 1993-1996. T2D status was based on
self-report with confirmation by administrative data. Serum CRP and TGs and
plasma adiponectin and leptin were measured ~10 y after baseline in a subset (n =
10,008) of participants. RRR was applied to dietary data and biomarker
information of 10,008 MEC participants in the combined population and in each
ethnic/racial group. RRR-derived dietary patterns, simplified by removal of foods
that were not found to be important, were subsequently evaluated for association
with T2D risk in 155,316 cohort members (8687 incident T2D cases diagnosed by
2010) by using Cox proportional hazards regression. Results: Combining
ethnic/racial groups, we identified a dietary pattern low in processed and red
meat, sugar-sweetened beverages, diet soft drinks, and white rice and high in
whole grains, fruit, yellow-orange vegetables, green vegetables, and low-fat
dairy that was inversely associated with CRP, TGs, and leptin and positively
related to adiponectin. Comparing extreme tertiles, the dietary pattern predicted
a 16-28% significantly lower T2D risk in the combined study population and also
separately in African Americans, Japanese Americans, Latinos, Native Hawaiians,
and whites. Ethnicity-specific derived patterns varied only modestly from the
overall pattern and resulted in comparable associations with T2D. Conclusion:
This identified dietary pattern may lower T2D risk through its impact on
adipokines, by lowering chronic inflammation and dyslipidemia across 5
ethnic/racial groups.
PMID- 29955703
TI - Genistein Prevents BRCA1 CpG Methylation and Proliferation in Human Breast Cancer
Cells with Activated Aromatic Hydrocarbon Receptor.
AB - Background: Previous studies have suggested a causative role for agonists of the
aromatic hydrocarbon receptor (AhR) in the etiology of breast cancer 1, early
onset (BRCA-1)-silenced breast tumors, for which prospects for treatment remain
poor. Objectives: We investigated the regulation of BRCA1 by the soy isoflavone
genistein (GEN) in human estrogen receptor alpha (ERalpha)-positive Michigan
Cancer Foundation-7 (MCF-7) and ERalpha-negative sporadic University of Arizona
Cell Culture-3199 (UACC-3199) breast cancer cells, respectively, with inducible
and constitutively active AhR. Methods: In MCF-7 cells, we analyzed the dose- and
time-dependent effects of GEN and (-)-epigallocatechin-3-gallate (EGCG) control,
selected as prototype dietary DNA methyltransferase (DNMT) inhibitors, on BRCA-1
expression after AhR activation with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
and in TCDD-washout experiments. We compared the effects of GEN and EGCG on BRCA1
cytosine-phosphate-guanine (CpG) methylation and cell proliferation. Controls for
DNA methylation and proliferation were changes in expression of DNMT-1, cyclin
D1, and p53, respectively. In UACC-3199 cells, we compared the effects of GEN and
alpha-naphthoflavone (alphaNF; 7,8-benzoflavone), a synthetic flavone and AhR
antagonist, on BRCA1 expression and CpG methylation, cyclin D1, and cell growth.
Finally, we examined the effects of GEN and alphaNF on BRCA1, AhR-inducible
cytochrome P450 (CYP)-1A1 (CYP1A1) and CYP1B1, and AhR mRNA expression. Results:
In MCF-7 cells, GEN exerted dose- and time-dependent preventative effects against
TCDD-dependent downregulation of BRCA-1. After TCDD washout, GEN rescued BRCA-1
protein expression while reducing DNMT-1 and cyclin D1. GEN and EGCG reduced
BRCA1 CpG methylation and cell proliferation associated with increased p53. In
UACC-3199 cells, GEN reduced BRCA1 and estrogen receptor-1 (ESR1) CpG
methylation, cyclin D1, and cell growth while inducing BRCA-1 and CYP1A1.
Conclusions: Results suggest preventative effects for GEN and EGCG against BRCA1
CpG methylation and downregulation in ERalpha-positive breast cancer cells with
activated AhR. GEN and flavone antagonists of AhR may be useful for reactivation
of BRCA1 and ERalpha via CpG demethylation in ERalpha-negative breast cancer
cells harboring constitutively active AhR.
PMID- 29955704
TI - Associations between Parenting Style and Parent and Toddler Mealtime Behaviors.
AB - Background: By the time a child is 24 mo old, 50% of parents report experiencing
picky eating behaviors with their child. These behaviors include consuming an
inadequate dietary variety, eating the same foods repeatedly, and an
unwillingness to try either new or familiar foods. Previous research has
established relations with regard to the impact of parent feeding strategies on
child mealtime behaviors and how parent feeding strategies are influenced by
parenting style; however, to our knowledge, no studies have investigated whether
there is an association between parenting style and perceived child mealtime
behaviors specifically related to picky eating. Objective: The purpose of this
study was to investigate whether a relation exists between general parenting
style and both parent feeding strategies and perceived picky eater and non-picky
eater (NPE) behaviors. Methods: Parents of 2- to 5-y-old children (n = 525)
completed 2 online surveys: 1) the Mealtime Assessment Survey, which measures the
frequency of parent and child mealtime behaviors, and 2) the Parenting Styles and
Dimensions Questionnaire, which measures authoritative, authoritarian, and
permissive parenting styles. Spearman's correlation analysis was conducted to
determine the relations between parenting style and mealtime behavior. Results:
Positive correlations were found between an authoritative parenting style and NPE
behaviors, as well as parent mealtime strategies that promote positive eating
habits. Authoritarian and permissive parenting styles were positively correlated
with child behaviors associated with picky eating and parent mealtime strategies
that can negatively influence child feeding. Conclusions: These findings suggest
that a relation exists between general parenting style and both parent and child
mealtime behaviors; however, the directionality of the relation remains unknown.
The positive correlations seen within the authoritative parenting style with
regard to NPE behaviors suggest the use of authoritative feeding methods to
overcome feeding difficulties.
PMID- 29955705
TI - Multiple Vitamin K Forms Exist in Dairy Foods.
AB - Background: The plant-based form of vitamin K (phylloquinone, vitamin K-1) has
been well quantified in the US diet. Menaquinones (vitamin K-2) are another class
of vitamin K compounds that differ from phylloquinone in the length and
saturation of their side chain, but they have not been well characterized in
foods. Objectives: The objectives of this study were to 1) quantify phylloquinone
and the different forms of menaquinones [menaquinone (MK) 4-MK13] in milk,
yogurt, Greek yogurt, creams, and cheeses and 2) compare the menaquinone contents
of full-fat, reduced-fat, and nonfat dairy products. Methods: All dairy samples
were either obtained from the USDA National Food and Nutrient Analysis Program or
purchased from retail outlets. Phylloquinone and menaquinone concentrations in
these dairy products were quantified by mass spectrometry technology. Results:
Full-fat dairy products contained appreciable amounts of menaquinones, primarily
in the forms of MK9, MK10, and MK11. We also measured modest amounts of
phylloquinone, MK4, MK8, and MK12 in these products. In contrast, there was
little MK5-7 or MK13 detected in the majority of dairy products. The total
vitamin K contents of soft cheese, blue cheese, semi-soft cheese, and hard cheese
were (means +/- SEMs): 506 +/- 63, 440 +/- 41, 289 +/- 38, and 282 +/- 5.0 ug/100
g, respectively. Nonfermented cheeses, such as processed cheese, contained lower
amounts of vitamin K (98 +/- 11 ug/100 g). Reduced-fat or fat-free dairy products
contained ~5-22% of the vitamin K found in full-fat equivalents. For example,
total vitamin K contents of full-fat milk (4% fat), 2%-fat milk, 1%-fat milk, and
nonfat milk were 38.1 +/- 8.6, 19.4 +/- 7.7, 12.9 +/- 2.0, and 7.7 +/- 2.9 ug/100
g, respectively. Conclusions: To the best of our knowledge, this is the first
report of menaquinone contents of US dairy products. Findings indicate that the
amount of vitamin K contents in dairy products is high and proportional to the
fat content of the product.
PMID- 29955706
TI - Annatto Tocotrienol Attenuates NLRP3 Inflammasome Activation in Macrophages.
AB - Accumulating evidence suggests that aberrant innate immunity is closely linked to
metabolic diseases, including type 2 diabetes. In particular, activation of the
NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and
subsequent secretion of interleukin 1beta (IL-1beta) are critical determinants
that precipitate disease progression. The seeds of annatto (Bixa orellana L.)
contain tocotrienols (T3s), mostly (>90%) in the delta form (deltaT3). The aim of
this study was to determine whether annatto T3 is effective in attenuating NLRP3
inflammasome activation in macrophages. Our results showed that annatto deltaT3
significantly attenuated NLRP3 inflammasome by decreasing IL-1beta reporter
activity, IL-1beta secretion, and caspase-1 cleavage against lipopolysaccharide
(LPS) followed by nigericin stimulation. With regard to mechanism, annatto
deltaT3 1) reduced LPS-mediated priming of the inflammasome and 2) dampened
reactive oxygen species production, the second signal required for assembly of
the NLRP3 inflammasome in macrophages. Our work suggests that annatto deltaT3 may
hold therapeutic potential for delaying the onset of NLRP3 inflammasome
associated chronic metabolic diseases.
PMID- 29955707
TI - Ingesting a Combined Carbohydrate and Essential Amino Acid Supplement Compared to
a Non-Nutritive Placebo Blunts Mitochondrial Biogenesis-Related Gene Expression
after Aerobic Exercise.
AB - Background: Whether load carriage (LC), an endurance exercise mode composed of
the aerobic component of traditional endurance exercise [e.g., cycle ergometry
(CE)] and contractile forces characteristic of resistive-type exercise, modulates
acute mitochondrial adaptive responses to endurance exercise and supplemental
nutrition [carbohydrate + essential amino acids (CHO+EAA)] is not known.
Objective: The aim of this study was to examine the effects of LC and CE, with or
without CHO+EAA supplementation, on acute markers of mitochondrial biogenesis.
Methods: Twenty-five adults performed 90 min of metabolically matched LC
(treadmill walking, wearing a vest equal to 30% of body mass) or CE exercise
during which CHO+EAA (46 g carbohydrate and 10 g essential amino acids) or non
nutritive control (CON) drinks were consumed. Muscle biopsy samples were
collected at rest (pre-exercise), post-exercise, and after 3 h of recovery to
assess citrate synthase activity and the expression of mRNA (reverse
transcriptase-quantitative polymerase chain reaction) and protein (Western blot).
Results: Citrate synthase and phosphorylated p38 mitogen-activated protein kinase
(p38 MAPK)Thr180/Tyr182 were elevated postexercise compared with pre-exercise
(time main effect, P < 0.05). Peroxisome proliferator-activated gamma-receptor
coactivator 1alpha (PGC-1alpha) expression was highest after recovery for CE
compared with LC (exercise-by-time effect, P < 0.05). Sirtuin 1 (SIRT1)
expression postexercise was higher for CON than for CHO+EAA treatments (drink-by
time, P < 0.05). Tumor suppressor p53 (p53), mitochondrial transcription factor A
(TFAM), and cytochrome c oxidase subunit IV (COXIV) expression was greater for
CON than for CHO+EAA treatments (drink main effect, P < 0.05). PGC-1alpha and p53
expressions were positively associated (P < 0.05) with TFAM (r = 0.629 and 0.736,
respectively) and COXIV (r = 0.465 and 0.461, respectively) expressions.
Conclusions: Acute mitochondrial adaptive responses to endurance exercise appear
to be largely driven by exogenous nutrition availability. Although CE upregulated
PGC-1alpha expression to a greater extent than LC, downstream signaling was the
same between modes, suggesting that LC, in large part, elicits the same acute
mitochondrial response as traditional, non-weight-bearing endurance exercise.
This trial was registered at clinicaltrials.gov as NCT01714479.
PMID- 29955708
TI - Toward a Better Understanding of Adherence to Micronutrient Powders: Generating
Theories to Guide Program Design and Evaluation Based on a Review of Published
Results.
AB - Background: The Global Alliance for Improved Nutrition is conducting theory
driven process evaluations of micronutrient powder (MNP) programs. Objective: The
aim was to generate preliminary theories about factors affecting adherence to
recommendations with regard to point-of-use fortification of foods with MNPs.
Methods: A literature search was conducted to identify documents with content
related to adherence to MNPs as an intervention provided at home to children 6-59
mo of age. Thirty-five studies and 6 program descriptions were identified. We
used thematic analyses to generate a comprehensive list of factors that could
influence adherence, followed by content analysis to quantify the results. We
developed a Program Impact Pathway to concretize the points at which the factors
identified affect the process of adherence. Results: In the set of documents
reviewed (n = 41), the most influential factors, measured by number of documents
reporting the factor having effect, were 1) caregivers' perception of positive
changes as a result of MNP use (n = 14), 2) caregivers' perceived child
acceptance of food with MNPs (n = 12), and 3) caregivers' forgetfulness (n = 11).
Behavior change communication channels (n = 13) and messages (n = 12) were the
most frequently reported program design features influencing caregiver knowledge
and subsequent adherence. Administration regimen (n = 10), which may be related
to caregivers' capacity to remember to give MNPs, was also a frequently cited
program design feature affecting adherence. Conclusions: The preponderance of
knowledge and perception factors may reflect an underlying theoretical bias among
researchers as to what they measure. To achieve programs that support greater
adherence, we need to adopt a cultural-ecological perspective to inform program
design in order to address a broader set of determinants. Studies that assess
progress across the impact pathway, particularly from adherence to biological
outcomes, would also provide guidance for evaluation studies, particularly when
time or other constraints limit the potential to measure biological outcomes.
PMID- 29955709
TI - Adherence to Canada's Food Guide Recommendations during Pregnancy: Nutritional
Epidemiology and Public Health.
AB - Background: In Canada, pregnant women are typically referred to Canada's Food
Guide (CFG), a set of national dietary recommendations designed to promote
adequate nutrient intake. Pregnant women are also advised to gain weight within
the Institute of Medicine guidelines, which differ by prepregnancy body mass
index (BMI). However, CFG recommendations do not account for prepregnancy BMI and
provide no guidance on "less healthy" (LH) foods. Objective: The aim of this
study was to score women's diets according to adherence to CFG recommendations
and consumption of LH foods and to examine differences between these diet scores
by prepregnancy BMI. Methods: Participants enrolled in the APrON (Alberta
Pregnancy Outcomes and Nutrition) prospective cohort study completed a 24-h
recall in their second trimester (n = 1630). A score was created on the basis of
each daily dietary CFG recommendation met, ranging from 0 to 9. The distribution
of consumption (grams per day) of 8 LH food groups was given a score of 0 (none)
or 1, 2, or 3 (representing the lowest, middle, or highest tertiles,
respectively) and summed giving a total LH score of 0-24. Results: There were few
differences in CFG recommendations met by prepregnancy BMI status, although fewer
women who were overweight or obese prepregnancy met the specific recommendation
to consume 7-8 servings of fruit or vegetables/d than did those who were under-
or normal weight (47% and 41% compared with 50% and 54%, respectively). Although
differences were small, women who were obese prepregnancy had lower CFG scores
(beta = -0.28; 95% CI:-0.53, -0.02) and higher LH scores (beta = 0.45; 95% CI:
0.04, 0.86) than did those who were normal weight. Conclusion: The study results
suggest that more attention may need to be paid to individualized counseling on
dietary recommendations that take account of prepregnancy BMI.
PMID- 29955710
TI - Lessons and Challenges from a 6-Month Randomized Pilot Study of Daily Ethanol
Consumption: Research Methodology and Study Design.
AB - Background: Observational studies and crossover feeding studies suggest that
moderate alcohol use may benefit cardiovascular risk, but we know of no long-term
randomized trials that have tested this hypothesis. Objective: We evaluated the
feasibility of an efficacy study of daily ethanol use in a 6-mo randomized pilot
study in adults at higher cardiovascular risk. Methods: In a double-blind,
randomized, controlled parallel-design trial, we screened 67 adults aged >=55 y
and randomly assigned 45 participants to consume 150 mL of an artificially
sweetened beverage with or without 10% grain alcohol daily for 6 mo. Participants
were asked to consume no other alcohol and returned monthly to receive the
beverage and undergo measurement of HDL cholesterol, liver function tests, and
complete blood counts. Results: Of the 45 randomly assigned participants, 39
completed the trial; the primary reason cited for attrition was inconvenience.
None of the participants reported problem drinking or developed any serious
adverse events or abnormal biochemical findings. However, we observed no
differences in concentrations of HDL cholesterol, HDL lipoprotein subclasses,
aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase,
mean corpuscular volume, or adiponectin between the alcohol and control arms,
suggesting that adherence was poor. Every participant accurately identified their
assigned beverage, most with great certainty. Conclusions: In this parallel
design pilot study of daily alcohol use, we observed none of the expected changes
in markers of alcohol intake, which suggests poor adherence to this pure alcohol
intervention. Our results suggest that long-term trials of alcohol consumption,
if they are conducted in light drinkers similar to these, must use pragmatic
designs for maximal feasibility. This study was registered at clinicaltrials.gov
as NCT01377727.
PMID- 29955711
TI - Food Security and the 2015-2030 Sustainable Development Goals: From Human to
Planetary Health: Perspectives and Opinions.
AB - Food security exists when "all people, at all times have physical and economic
access to sufficient, safe and nutritious food that meets their dietary needs and
food preferences for an active and healthy life"
(http://www.fao.org/wfs/index_en.htm). Close to 800 million individuals do not
have access to enough food, >2 billion individuals experience key micronutrient
deficiencies, and ~60% of individuals in low-income countries are food insecure.
Food insecurity negatively affects human physical, social, emotional, and
cognitive development throughout the life course and is a major social and
environmental disruptor with serious repercussions for planetary health (i.e.,
the health of human civilization and the state of the natural systems on which it
depends). Food security is related to all of the United Nations Sustainable
Development Goals (SDGs). Improved food security governance based on sound,
equitable, and sustainable food systems that benefit from modern information and
sustainable and equitable agricultural technologies is essential for countries to
meet the SDGs.
PMID- 29955712
TI - Research Priorities for Studies Linking Intake of Low-Calorie Sweeteners and
Potentially Related Health Outcomes: Research Methodology and Study Design.
AB - Background: In a world of finite research funding, efforts to prioritize future
research topics are increasingly necessary. Objective: The aim of this study was
to identify and prioritize the direction of future research in the broad area of
low-calorie sweetener (LCS) intake and potentially related health outcomes by
using a novel method that incorporates evidence mapping in the Agency for
Healthcare Research and Quality's Future Research Needs (FRN) process. Methods: A
diverse expert stakeholder panel was convened and engaged to identify research
gaps and prioritize future research needs. An independent research team hosted a
number of interactive webinars and elicited feedback through surveys and
individual interviews with the stakeholder panel, which included policymakers,
lay audience members, health providers, a research funder, individuals with food
industry experience, and researchers of several different specialties. Results:
The stakeholder panel generated and ranked a list of 18 FRN questions across 5
broad research areas. Overall, stakeholder panel members unanimously agreed that
the research questions that will have the largest public health impact are those
that address outcomes related to body weight, appetite, and dietary intake.
Although the LCSs included in this FRN project have all been Generally Recognized
as Safe by the FDA or approved as food additives, the recurrent concerns and
confusions with regard to the "safety" of LCSs by consumers underscore the
importance of communicating the science to the general public. Conclusion: Our
project provides evidence that engaging a diverse expert stakeholder panel is an
effective method of translating gaps in nutrition research into prioritized areas
of future research.
PMID- 29955713
TI - Emulsification Increases the Acute Ketogenic Effect and Bioavailability of Medium
Chain Triglycerides in Humans: Protein, Carbohydrate, and Fat Metabolism.
AB - Background: Lower-brain glucose uptake is commonly present before the onset of
cognitive deterioration associated with aging and may increase the risk of
Alzheimer disease. Ketones are the brain's main alternative energy substrate to
glucose. Medium-chain triglycerides (MCTs) are rapidly beta-oxidized and are
ketogenic but also have gastrointestinal side effects. We assessed whether MCT
emulsification into a lactose-free skim-milk matrix [emulsified MCTs (MCT-Es)]
would improve ketogenesis, reduce side effects, or both compared with the same
oral dose of MCTs consumed without emulsification [nonemulsified MCTs (MCT-NEs)].
Objectives: Our aims were to show that, in healthy adults, MCT-Es will induce
higher ketonemia and have fewer side effects than MCT-NEs and the effects of MCT
NEs and MCT-Es on ketogenesis and plasma medium-chain fatty acids (MCFAs) will be
dose-dependent. Methods: Using a metabolic study day protocol, 10 healthy adults
were each given 3 separate doses (10, 20, or 30 g) of MCT-NEs or MCT-Es with a
standard breakfast or no treatment [control (CTL)]. Blood samples were taken
every 30 min for 4 h to measure plasma ketones (beta-hydroxybutyrate and
acetoacetate), octanoate, decanoate, and other metabolites. Participants
completed a side-effects questionnaire at the end of each study day. Results:
Compared with CTL, MCT-NEs increased ketogenesis by 2-fold with no significant
differences between doses. MCT-Es increased total plasma ketones by 2- to 4-fold
in a dose-dependent manner. Compared with MCT-NEs, MCT-Es increased plasma MCFA
bioavailability (F) by 2- to 3-fold and decreased the number of side effects by
~50%. Conclusions: Emulsification increased the ketogenic effect and decreased
side effects in a dose-dependent manner for single doses of MCTs <=30 g under
matching conditions. Further investigation is needed to establish whether
emulsification could sustain ketogenesis and minimize side effects and therefore
be used as a treatment to change brain ketone availability over a prolonged
period of time. This trial was registered at clinicaltrials.gov as NCT02409927.
PMID- 29955714
TI - The Decline in Vitamin Research Funding: A Missed Opportunity?
AB - Background: The National Nutrition Research Roadmap has called for support of
greater collaborative, interdisciplinary research for multiple areas of nutrition
research. However, a substantial reduction in federal funding makes responding to
these calls challenging. Objectives: The objectives of this study were to examine
temporal trends in research funding and to discuss the potential consequences of
these trends. Methods: We searched the NIH RePORTER database to identify NIH
research grants and USASpending to identify National Science Foundation and USDA
research grants awarded from 1992 to 2015. We focused on those that pertained to
vitamin research. For the years 2000 to 2015, we examined funding trends for
different vitamins, including vitamins A, B (one-carbon B-vitamins were
considered separately from other B-vitamins), C, D, E, and K. Results: From 1992
to 2015, total federal research spending increased from ~$14 to $45 billion (2016
US dollars). Although vitamin research spending increased from ~$89 to $95
million, the proportion of grants awarded for vitamin research declined by more
than two-thirds, from 0.65% in 1992 to 0.2% in 2015. Federal agencies awarded
6035 vitamin research grants over the time period, with vitamin A associated with
the most research projects per year on average (n = 115) and vitamin K the fewest
(n = 8). Vitamin D research projects were associated with the greatest average
yearly project value ($34.8 million). Conclusions: Vitamin research has faced a
disproportionate decline in research funding from 1992 to 2015. Insufficient
federal research funding streams risk stalling progress in vitamin research and
leaving important advancements unrealized.
PMID- 29955715
TI - Trends in Cruciferous Vegetable Consumption and Associations with Breast Cancer
Risk: A Case-Control Study.
AB - Background: The chemopreventive activities of cruciferous vegetables were
recognized in the early 1990s, followed by a growth of evidence in various cancer
models, including breast cancer. To our knowledge, no studies have examined
whether consumption of cruciferous vegetables has changed accordingly, and what
impact, if any, on breast cancer risk may have resulted. Objective: The time
trend in cruciferous vegetable intake was investigated between 1982 and 1998, and
its associations with breast cancer risk were examined. Methods: In a hospital
based case-control study in 1491 patients with breast cancer and 1482 controls,
loess curves were constructed to describe the relation between median consumption
of cruciferous vegetables and year of admission. ORs and 95% CIs were calculated
with unconditional logistic regression, adjusting for age, year of admission,
family income, body mass index, cigarette smoking, age at menarche, parity, age
at first birth, family history of breast cancer, hormone replacement therapy, and
total meat intake. Results: Consumption patterns differed between cases and
controls. A slow but steady increase in cruciferous vegetable intake was observed
in the cases, although among controls, cruciferous vegetable consumption
increased from 1982 to 1987, reached a plateau during 1988-1992, and then
declined from 1993 to 1998. Accordingly, although an overall inverse association
with breast cancer risk was observed for cruciferous vegetable intake (highest
compared with lowest quartile-OR: 0.68; 95% CI: 0.55, 0.86; P-trend = 0.0006),
the inverse association tended to be more pronounced within more recent-year
strata, with an OR of 0.52 (95% CI: 0.33, 0.83) for 1993-1998 compared with an OR
of 0.89 (95% CI: 0.64, 1.23) for 1982-1987. Conclusions: The consumption of
cruciferous vegetables increased during the past 2 decades, showing different
trends in cases and controls. The subtle but sustained increase in cruciferous
vegetable intake reported by the cases could influence association studies with
breast cancer risk.
PMID- 29955716
TI - Phosphorus Supplementation Mitigated Food Intake and Growth of Rats Fed a Low
Protein Diet.
AB - Background: Low protein intake is associated with various negative health
outcomes at any life stage. When diets do not contain sufficient protein,
phosphorus availability is compromised because proteins are the major sources of
phosphorus. However, whether mineral phosphorus supplementation mitigates this
problem is unknown, to our knowledge. Objective: Our goal was to determine the
impact of dietary phosphorus supplementation on food intake, weight gain, energy
efficiency, body composition, blood metabolites, and liver histology in rats fed
a low-protein diet for 9 wk. Methods: Forty-nine 6-wk-old male Sprague-Dawley
rats were randomly allocated to 5 groups and consumed 5 isocaloric diets ad
libitum that varied only in protein (egg white) and phosphorus concentrations for
9 wk. The control group received a 20% protein diet with 0.3% P (NP-0.3P). The 4
other groups were fed a low-protein (10%) diet with a phosphorus concentration of
0.015%, 0.056%, 0.1%, or 0.3% (LP-0.3P). The rats' weight, body and liver
composition, and plasma biomarkers were then assessed. Results: The addition of
phosphorus to the low-protein diet significantly increased food intake, weight
gain, and energy efficiency, which were similar among the groups that received
0.3% P (LP-0.3P and NP-0.3P) regardless of dietary protein content. In addition,
phosphorus supplementation of low-protein diets reduced plasma urea nitrogen and
increased total body protein content (defatted). Changes in food intake and
efficiency, body weight and composition, and plasma urea concentration were
highly pronounced at a dietary phosphorus content <0.1%, which may represent a
critical threshold. Conclusions: The addition of phosphorus to low-protein diets
improved growth measures in rats, mainly as a result of enhanced energy
efficiency. A dietary phosphorus concentration of 0.3% mitigated detrimental
effects of low-protein diets on growth parameters.
PMID- 29955717
TI - Effects of Dairy Consumption on Body Composition and Bone Properties in Youth: A
Systematic Review.
AB - Background: According to previous reviews, there is no clear evidence on the
effects of dairy consumption on body composition and bone properties in pediatric
populations. There is a need for further assessment of existing findings and the
methodologic quality of studies before summarizing the evidence. Objective: The
aim of the study was to assess the quality, methodologies, and substantive
findings of randomized controlled trials (RCTs) that examined the effects of
dairy consumption on body size, body composition, and bone properties in children
and adolescents. Methods: After searching PubMed and Google Scholar up to
December 2016, 15 RCTs were retained and included in this systematic review for
further analysis. The quality of the included studies was assessed via the Jadad
scale; detailed methodologic and statistical characteristics were evaluated, and
the main findings were summarized. Results: The effects of dairy consumption were
found to be significant for bone structure and nonsignificant for body size and
composition. Eight of the 11 RCTs that assessed bone found significant effects (P
< 0.05) for bone mineral content and bone mineral density (BMD), with an average
8% increase in BMD after 16 mo of dairy consumption. Conversely, significant
effects (P < 0.05) were found only in 2 of the 14 RCTs that focused on body size
(i.e., height and weight) and in only 1 of the 11 RCTs that focused on body
composition (i.e., lean mass). Conclusions: The systematic consumption of dairy
products may benefit bone structure and development, but it does not appear to
affect body composition or body size in children and adolescents. On the basis of
the Jadad scale, the methodologic quality of the 15 RCTs was rated as good
overall. However, there were methodologic disparities and limitations that may
have led to nonsignificant results, particularly for body size and composition.
Future RCTs designed to address these limitations are warranted.
PMID- 29955718
TI - Bacteria and Bioactivity in Holder Pasteurized and Shelf-Stable Human Milk
Products.
AB - Background: Historically, Holder pasteurization has been used to pasteurize donor
human milk available in a hospital setting. There is extensive research that
provides an overview of the impact of Holder pasteurization on bioactive
components of human milk. A shelf-stable (SS) human milk product, created using
retort processing, recently became available; however, to our knowledge, little
has been published about the effect of retort processing on human milk.
Objective: We aimed to assess the ability of retort processing to eliminate
bacteria and to quantify the difference in lysozyme and secretory immunoglobulin
A (sIgA) activity between Holder pasteurized (HP) and SS human milk. Methods:
Milk samples from 60 mothers were pooled. From this pool, 36 samples were taken:
12 samples were kept raw, 12 samples were HP, and 12 samples were retort
processed to create an SS product. All samples were analyzed for total aerobic
bacteria, coliform bacteria, Bacillus cereus, sIgA activity, and lysozyme
activity. Raw samples served as the control. Results: One raw sample and 3 HP
samples contained B. cereus at the time of culture. There were no detectable
bacteria in SS samples at the time of culture. Raw samples had significantly
greater lysozyme and sIgA activity than HP and SS samples (P < 0.0001). HP
samples retained significantly more lysozyme and sIgA activity (54% and 87%,
respectively) than SS samples (0% and 11%, respectively). Conclusions: Human milk
processed using Holder pasteurization should continue to be screened for the
presence of B. cereus. Clinicians should be aware of the differences in the
retention of lysozyme and sIgA activity in HP and SS products when making feeding
decisions for medically fragile or immunocompromised infants to ensure that
patients are receiving the maximum immune protection.
PMID- 29955719
TI - Quinoa Seed Lowers Serum Triglycerides in Overweight and Obese Subjects: A Dose
Response Randomized Controlled Clinical Trial.
AB - Background: Quinoa (Chenopodium quinoa) is a pseudo-cereal originally cultivated
in the Andean region. The popularity of its seeds has increased in recent years
due to the claims of health benefits and superfood qualities. Studies to date on
the health benefits of quinoa have been restricted to animal models, and the
results provide weak to moderate evidence to support improved plasma lipid
profiles. Clinical trials in humans to examine the claims of health benefits of
quinoa are limited to a few prospective studies and one randomized trial carried
out in postmenopausal women. To our knowledge, no studies have been conducted in
the general population. Objective: The objective of this randomized clinical
trial was to investigate the effect of different quinoa doses (25 and 50 g/d) on
body composition, serum lipids and hormones, and nutrient intakes in overweight
and obese humans. Methods: This was a dose-response randomized, controlled,
single-blind trial with a parallel design (1 control and 2 treatment groups) that
compared the effect of 25 and 50 g quinoa/d in 50 overweight and obese
participants over a 12-wk intervention period. Results: Body composition,
nutrient intake, and total, LDL, and HDL cholesterol were not significantly
altered by quinoa consumption (P > 0.05). Mean serum triglyceride (TG)
concentration was reduced significantly in the 50-g quinoa group from 1.14 to
0.72 mmol/L at 12 wk (P < 0.05). The prevalence of metabolic syndrome (MetS) was
also reduced in this group by 70%. No significant changes in TGs were observed in
the control and 25-g quinoa groups. The prevalence of MetS was reduced by 40%
(from n = 7 at baseline to n = 4 at 12 wk) in the 25-g group. Conclusions: The
consumption of 50 g quinoa/d lowers serum TGs in overweight and obese
participants and reduces the prevalence of MetS. This trial was registered at
clinicaltrials.gov as UTN U1111-1175-470.
PMID- 29955720
TI - Multiple Reaction Monitoring Profiling to Assess Compliance with an Almond
Consumption Intervention.
AB - Background: Almonds are extremely rich sources of lipids and flavonoids, and
their consumption is associated with several health benefits. However, there are
no analytical methods available to document compliance with prescribed or self
reported chronic almond consumption. Objective: The aim was to use an analytical
approach that identifies metabolic profiles associated with long-term almond
consumption to ascertain compliance with prescribed consumption. Methods: A
multiple reaction monitoring (MRM)-profiling strategy was designed to isolate
metabolic changes in erythrocytes after 12 wk of almond consumption. MRM
profiling data acquisition and analysis involve performing separate discovery and
screening steps to detect molecular features related to metabolic changes between
experimental groups. Samples used for this research were erythrocytes recovered
at baseline, after 12 wk of almond consumption (W12-almond group), and after 12
wk of a nut-free diet (W12-control group). For the MRM-profiling discovery step,
representative samples (pools) of erythrocytes from individuals of all groups
were interrogated by precursor ion and neutral loss scan experiments on the basis
of previous knowledge of chemical functional groups present in the samples. The
outputs of the discovery phase were methods used for the MRM-profiling screening
phase to interrogate individual samples on the basis of fast-MRM measurements. In
addition, we screened the literature for flavonoids identified in almond skins
and included them for individual sample screening. Results: Of the 254 m/z values
monitored, 5 ratios and combinations of specific ions with receiver operating
characteristic curve AUCs >0.89 provided a sensitivity of 74.2% and a specificity
of 90% for blind samples presented in the model. Eight of the 31 participants
(25.8%) in the W12-almond group and 3 of the 30 (10%) participants in the W12
control group were misclassified by all 5 ratios. Ratios and combinations of
specific transitions were mainly related to membrane lipids. Conclusion: The
misclassifications observed as a result of ratio performance evaluation may
indicate noncompliance as supported by the dietary intake data. The parent trial
was registered at www.clinicaltrials.gov as NCT02360787.
PMID- 29955721
TI - Iron, Oxidative Stress, and Delta9 Stearoyl-CoenzymeA Desaturase Index
(C16:1/C16:0): An Analysis Applying the National Health and Nutrition Examination
Survey 2003-04.
AB - Background: Stearoyl-coenzyme A desaturase (SCD) is a key enzyme in fatty acid
metabolism, and elevated SCD activity is associated with multiple adverse health
outcomes. Diet, hormone levels, and environmental exposures are potential factors
affecting SCD activity. Less is known about the relationship between
micronutrients, including iron, and SCD activity. Objective: The aim of this
study was to investigate the association between serum ferritin level, a
biomarker of circulating iron levels, and the Delta9 desaturase index
(C16:1/C16:0), a biomarker of estimated SCD activity, among women in the United
States. Methods: The association between serum ferritin and the Delta9 desaturase
index was assessed in a cross-sectional study of 447 female participants, aged 20
49 y, from NHANES 2003-2004. The multivariate analyses were performed utilizing
generalized linear modeling, adjusting for potential confounders. Mediation of
the relationship between serum ferritin and Delta9 desaturase index by gamma
glutamyltranspeptidase (GGT), a biomarker of oxidative stress, was also assessed.
Results: Increased ferritin was significantly associated with a higher Delta9
desaturase index. Adjusting for waist circumference, age, race, and cotinine
levels, an interquartile range increase in serum ferritin corresponded to 3.92%
(95% CI: 0.88%, 7.05%) higher Delta9 desaturase index. GGT, the biomarker used to
measure oxidative stress level, did not appear to mediate the association between
ferritin and Delta9 desaturase index. After stratifying by pregnancy status,
these associations were limited to nonpregnant individuals. Conclusions: Elevated
SCD activity may be associated with increased iron storage inside the human body;
the association did not appear to be mediated via oxidative stress, as estimated
by GGT levels.
PMID- 29955722
TI - Addition of Exogenous gamma-Glutamyl Hydrolase Eliminates the Need for Lengthy
Incubation of Whole-Blood Lysate for Quantitation of Folate Vitamers by High
Performance Liquid Chromatography-Tandem Mass Spectrometry.
AB - Background: Measurement of folate monoglutamates by HPLC-tandem mass spectrometry
(HPLC-MS/MS) in whole-blood lysate (WBL) requires lengthy incubation before
analysis, risking degradation of labile folate vitamers. Objective: We explored
whether the addition of a commercially available recombinant exogenous gamma
glutamyl hydrolase (exoGGH) enzyme reduced the required incubation time of WBL
for measurement of folate as monoglutamates. Methods: For conventional
deglutamylation of polyglutamates, WBL was incubated for 4 h at 37 degrees C.
Alternatively, we added exoGGH to WBL at varying concentrations (1-10 ug/mL) and
incubation times (0-90 min). We also investigated modifications to the sample
diluent (pH, ascorbic acid compared with sodium ascorbate, and ascorbate
concentration). Finally, we tested the effect of the enzyme in different sample
types: WBL from frozen whole blood compared with frozen WBL or with frozen washed
RBCs. Samples (n <= 15/experiment) were analyzed by HPLC-MS/MS for 6 folate
monoglutamates and 5-methyltetrahydrofolate diglutamate. Results: Optimal
deconjugation of folate polyglutamates was achieved by using 1% ascorbic acid and
5 ug enzyme/mL WBL, requiring <=30 min incubation time to achieve complete folate
recovery as monoglutamates. This treatment resulted in similar folate
concentrations as conventional deglutamylation (4 h at 37 degrees C). The exoGGH
enzyme was effective in samples stored frozen as whole blood and as WBL. However,
the extended thaw time of whole blood resulted in 5-methyltetrahydrofolate loss
and unacceptable changes to the non-methyl folate concentration. Total folate
(with exoGGH) measured in washed RBCs was ~15% lower than RBC folate calculated
from WBL concentrations (conventional deglutamylation). Conclusions: The use of
exoGGH minimized incubation time and thus may avoid degradative losses of labile
folate forms during sample preparation. The lower folate results in washed RBCs
may be due to inadequate packing of RBCs, among other unidentified factors. A
larger study is required to confirm the lack of differences in folate
concentrations determined with and without the use of exoGGH.
PMID- 29955723
TI - Diet Soda and Sugar-Sweetened Soda Consumption in Relation to Incident Diabetes
in the Northern Manhattan Study.
AB - Background: Artificially (diet) and sugar-sweetened (regular) soda consumption
have been associated with an increased risk of diabetes, but the literature on
diet soda is inconsistent and the mechanisms unclear. Objective: We examined the
relation between diet soda and regular soda consumption with the risk of incident
diabetes in a longitudinal multiethnic population-based cohort. Methods: The
study population included 2019 participants (mean +/- SD age: 69 +/- 10 y; 64%
women; 23% white, 22% black, 53% Hispanic) in the Northern Manhattan Study who
were free of diabetes and stroke at baseline. Soda consumption was assessed by a
food-frequency questionnaire at baseline and examined continuously and
categorically (<1/mo: sugar-sweetened = 908, diet = 1615; 1/mo-6/wk: sugar
sweetened = 830, diet = 298; daily: sugar-sweetened = 281, diet = 106). Weibull
regression models were used to estimate the associations between soda consumption
and incident diabetes, adjusting for demographics and vascular risk factors
including body mass index (BMI) and calorie consumption. Results: During a mean
+/- SD follow-up of 11 +/- 5 y, 368 participants developed diabetes. Sugar
sweetened soda was positively associated with incident diabetes (per soda per day
HR = 1.15, 95% CI: 1.02, 1.31). The observed association between diet soda and
elevated risk of diabetes was largely explained by BMI at the time of diet
assessment, though the association remained strong and independent of BMI among
those who were overweight or obese (daily compared to <1/mo: HR = 1.63, 95% CI:
1.04, 2.55). Conclusions: This study supports the importance of sugar-sweetened
beverage consumption in the diabetes epidemic. However, the results support
previous studies suggesting that switching to artificially sweetened diet
beverages may not lower the risk of diabetes, as diet soda consumption cannot be
ruled out as an independent diabetes risk factor.
PMID- 29955724
TI - Web-Based Recruitment and Survey Methodology to Maximize Response Rates from
Followers of Popular Diets: the Adhering to Dietary Approaches for Personal Taste
(ADAPT) Feasibility Survey.
AB - Background: Although there is interest in popular diets such as vegan and
vegetarian, Paleo, and other "whole food" diets, existing cohort studies lack
data for these subgroups. The use of electronic data capture and Web-based
surveys in nutrition research may be valuable for future studies by allowing
targeting of specific dietary subgroups. Objective: The aim was to perform a
Feasibility Survey (FS) to assess the practicality of Web-based research methods
to gather data and to maximize response rates among followers of popular diets.
Methods: The FS was an open, voluntary, 15-min survey conducted over 8 wk in the
summer of 2015. Recruitment targeted self-identified followers of popular diets
from a convenience sample, offering no incentives, via social media and e
newsletters shared by recruitment partners. Feasibility was assessed by number of
responses, survey completion rate, distribution of diets, geographic location,
and willingness to participate in future research. Results: A total of 14,003
surveys were initiated; 13,787 individuals consented, and 9726 completed the
survey (71% of consented). The numbers of unique visitors to the questionnaire
site, view rate, and participation rate were not captured. Among respondents with
complete demographic data, 83% were female and 93% were white. Diet designations
were collapsed into the following groups: whole-food, plant-based (25%); vegan
and raw vegan (19%); Paleo (14%); try to eat healthy (11%); vegetarian and
pescatarian (9%); whole food (8%); Weston A Price (5%); and low-carbohydrate (low
carb) (4%). Forced-response, multiple-choice questions produced the highest
response rates (0-2% selected "prefer not to answer"). The percentage who were
willing to complete future online questionnaires was 86%, diet recall was 93%,
and food diary was 75%; the percentages willing to provide a finger-stick blood
sample, venipuncture blood sample, urine sample, and stool sample were 60%, 44%,
58%, and 42%, respectively. Conclusions: This survey suggests that recruiting
followers of popular diets is feasible with the use of Web-based methods. The
unbalanced sample with respect to sex and race/ethnicity could be corrected with
specific recruitment strategies using targeted online marketing techniques.
PMID- 29955725
TI - Dietary Uridine Decreases Tumorigenesis in the ApcMin/+ Model of Intestinal
Cancer.
AB - Background: Dietary deoxyuridine and uridine have been shown to have opposing
effects on neural tube defect (NTD) incidence in the serine
hydroxymethyltransferase 1 (Shmt1+/- ) mouse model of folate-responsive NTDs,
which are mediated by changes in de novo thymidylate biosynthesis. Alterations in
folate-mediated one-carbon metabolism that protect against NTDs increased cancer
risk in some studies. Objective: This study examined the effects of the dietary
pyrimidine nucleosides uridine, thymidine, or deoxyuridine on intestinal
tumorigenesis in the ApcMin/+ mouse model [a mouse model lacking one copy of the
adenomatosis polypsis coli (APC) gene] of spontaneous intestinal tumor formation.
This study also evaluated the effects of uridine and deoxyuridine in culture
medium on antifolate efficacy in Caco-2 and HeLa cell lines. Methods: ApcMin/+
male mice (n = 10-14/group) were fed folate-deficient diets containing uridine,
thymidine, or deoxyuridine from weaning until 17 wk of age. Total intestinal
tumors were analyzed and biomarkers of folate status and metabolism were
measured, including plasma folate concentrations, colon uracil content, and SHMT1
concentrations. Results: ApcMin/+ mice fed dietary uridine showed a 50% reduction
in total intestinal tumors, but neither dietary deoxyuridine nor thymidine
affected tumorigenesis. Dietary nucleoside supplementation also increased plasma
folate concentrations in ApcMin/+ mice, as has been observed in the Shmt1+/-
mouse model. Neither uridine nor deoxyuridine in culture media affected
antifolate efficacy in either HeLa or Caco-2 cell lines. Conclusions: Dietary
uridine, which is teratogenic in mice, decreases intestinal tumor formation in
the ApcMin/+ mouse model. Dietary uridine mimics the effect of the common
methylene tetrahydrofolate reductase (MTHFR) C677T variant in protecting against
colorectal cancer, while contributing to the risk of NTDs.
PMID- 29955726
TI - Higher n-6:n-3 Fatty Acid Intake Is Associated with Decreased Cardiometabolic
Risk Factors in a Racially Diverse Sample of Children.
AB - Background: Accumulating evidence implicates diet quality in childhood as playing
a significant role in adult cardiometabolic health. Polyunsaturated fatty acids
(PUFAs) of the n-6 (omega-6) and n-3 (omega-3) series contribute unique
protective effects against cardiometabolic disease. As such, the ratio between n
6 and n-3 PUFAs is a dietary metric of interest in the early life span, although
an optimum intake ratio has yet to be determined. Objective: This cross-sectional
study assesses relations between the ratio of total n-6:n-3 PUFA intake and
cardiometabolic risk factors in a racially diverse sample of children (n = 191)
from the Admixture Mapping of Ethnic and Racial Insulin Complex Outcomes
(AMERICO) study. Methods: Outcome measures included waist circumference, lipid
concentrations, fasting glucose, and two 24-h dietary recalls from boys and girls
aged 7-12 y who self-reported as European American (n = 81), African American (n
= 55), or Hispanic American (n = 55). Linear regression analyses were used to
assess associations between predictors of interest and outcomes after adjusting
for covariates. Results: PUFA intake reflected in the n-6:n-3 ratio was inversely
associated with concentrations of total and LDL cholesterol [beta +/- SE: -0.359
+/- 0.107 (P = 0.001) and -0.189 +/- 0.069 (P = 0.007), respectively].
Exploratory analyses showed that the intake of total n-6 PUFAs was not
significantly predictive of any cardiometabolic risk factor assessed, whereas
total n-3 PUFA intake was positively associated with concentrations of HDL
cholesterol (beta +/- SE: 0.114 +/- 0.042; P = 0.007). Conclusions: Results
suggest that the effect of n-6 and n-3 PUFA intake reflected in the ratio may be
largely driven by n-3 PUFAs in reducing 2 lipid cardiometabolic risk factors
among this multiethnic cohort of children. Until an ideal intake ratio is
determined, nutritional counseling should focus on meeting recommended levels of
both n-3 and n-6 PUFAs in order to establish beneficial childhood dietary
patterns that may positively influence adult cardiometabolic health.
PMID- 29955727
TI - Maternal Dietary Choline Status Influences Brain Gray and White Matter
Development in Young Pigs.
AB - Background: Choline is an essential nutrient that is pivotal to proper brain
development. Research in animal models suggests that perinatal choline deficiency
influences neuron development in the hippocampus and cortex, yet these
observations require invasive techniques. Objective: This study aimed to
characterize the effects of perinatal choline deficiency on gray and white matter
development with the use of noninvasive neuroimaging techniques in young pigs.
Methods: During the last 64 d of the 114-d gestation period Yorkshire sows were
provided with a choline-sufficient (CS) or choline-deficient (CD) diet, analyzed
to contain 1214 mg or 483 mg total choline/kg diet, respectively. Upon farrowing,
pigs (Sus scrofa domesticus) were allowed colostrum consumption for <=48 h, were
further stratified into postnatal treatment groups, and were provided either CS
or CD milk replacers, analyzed to contain 1591 or 518 mg total choline/kg diet,
respectively, for 28 d. At 30 d of age, pigs were subjected to MRI procedures to
assess brain development. Gray and white matter development was assessed through
voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) to assess
the effects of prenatal and postnatal dietary choline status. Results: VBM
analysis indicated that prenatally CS pigs exhibited increased (P < 0.01) gray
matter in the left and right cortex compared with prenatally CD pigs. Analysis of
white matter indicated that prenatally CS pigs exhibited increased (P < 0.01)
white matter in the internal capsule, putamen-globus pallidus, and right cortex
compared with prenatally CD pigs. No postnatal effects (P > 0.05) of choline
status were noted for VBM analyses of gray and white matter. TBSS also showed no
significant effects (P > 0.05) of prenatal or postnatal choline status for
diffusion values along white matter tracts. Conclusions: Observations from this
study suggest that prenatal choline deficiency results in altered cortical gray
matter and reduced white matter in the internal capsule and putamen of young
pigs. With the use of noninvasive neuroimaging techniques, results from our study
indicate that prenatal choline deficiency greatly alters gray and white matter
development in pigs, thereby providing a translational assessment that may be
used in clinical populations.
PMID- 29955728
TI - Narrative Review of Culinary Interventions with Children in Schools to Promote
Healthy Eating: Directions for Future Research and Practice.
AB - Policymakers, scientists, and food and nutrition practitioners suggest that there
is a societal decline in culinary skills, which is predictive of poor dietary
habits contributing to childhood obesity. A narrative review was conducted to
critically evaluate culinary skill interventions for children ages 5-12 y in
schools to identify specific programs and programmatic factors associated with
improvement in the quality of diet, body mass index (BMI), and positive changes
in psychosocial variables. The culinary interventions were implemented in urban
and rural areas in the United States, Australia, and England. PubMed and Medline,
the Cochrane database, and a hand-search of publications identified 131 articles;
6 articles were selected for further examination on the basis of the inclusion
criteria. Study designs included 1 randomized controlled trial and 5 quasi
experimental studies. Three interventions were grounded in behavioral theory, of
which 2 incorporated the Social Cognitive Theory framework. The target population
and setting included children and early adolescents in schools. The study
methodology primarily included cooking classes combined with nutrition education
lessons, parent and community components, gardening classes, tasting sessions,
school lunchroom components, trips to a farmers market, or visits to a
restaurant. Qualitative evaluations of the programs indicated positive findings
in terms of program appeal and improvement in cooking skills and healthy eating.
Quantitative analysis indicated improvement in food preferences, cooking skills,
cooking self-efficacy, cooking behavioral intentions, food-preparation frequency,
knowledge, healthy dietary intake, BMI, and blood pressure. The findings from
this review support a positive relation between culinary interventions with
children in schools and improvement in cooking skills, consumption of a healthy
diet, and positive changes in anthropometric assessments. This review also
suggests that integration with the academic curriculum and school lunch program
may be potential avenues to explore for improving the longevity and success of
the cooking programs. Further research should emphasize rigorous methodologic
standards, develop theory-based standardized frameworks, and evaluate long-term
effects of culinary interventions.
PMID- 29955729
TI - Capturing Changes in HIV-Infected Breastfeeding Mothers' Cognitive Processes from
Before Delivery to 5 Months Postpartum: An Application of the Pile-Sorting
Technique in Haiti.
AB - Background: The cognitive processes involved in individuals' perceptions and
prioritization of information, and how these change with experience or exposure
to interventions, are rarely examined in the evaluation of nutrition
interventions. Exclusive breastfeeding counseling is a common infant and young
child feeding intervention and is used to promote HIV-free survival in the
prevention of mother-to-child transmission programs. However, it is often
designed without adequate attention to the changes in mothers' perceptions over
the course of their early breastfeeding experiences. Objective: The aim of this
study was to identify HIV-infected breastfeeding mothers' cognitive structure
(their organization of messages and ideas) of infant feeding messages and to
characterize whether their cognitive organization of infant feeding messages
changed from pregnancy through the first 5 mo postpartum. Methods: With the use
of semistructured interviews and the cognitive mapping technique of pile sorting,
we interviewed 30 HIV-infected breastfeeding mothers in Port-au-Prince, Haiti. We
asked them to sort and rate 18 infant feeding messages 3 times (during pregnancy,
0- to 1-mo postpartum, and 3- to 5-mo postpartum). We analyzed their responses by
using multidimensional scaling, property fitting, and partition analyses.
Results: At all 3 visits, we found consistency in women's cognitive mapping of
messages. For example, mothers consistently differentiated messages pertinent for
exclusive breastfeeding compared with those that pertained to other practices.
However, subtle variations in mothers' cognition over time were also evident,
particularly at 0- to 1-mo postpartum, when message proximity was tightly
clustered compared with the earlier and later periods. Conclusions: We conclude
that mothers share a common cognitive organization of infant feeding messages and
that this organization changes over time. Attention to variations in cognition
can support context-sensitive, patient-centered counseling by practitioners and
improve the effectiveness of nutrition interventions. Pile sorting is an
efficient, systematic technique to examine cognitive processes related to health
and nutrition.
PMID- 29955730
TI - Scaling Up Breastfeeding Programs in Mexico: Lessons Learned from the Becoming
Breastfeeding Friendly Initiative.
AB - Background: Given the magnitude of the health and economic burden of inadequate
breastfeeding practices in Mexico, there is an urgency to improve breastfeeding
practices to increase the health and well-being of children and mothers. The
Becoming Breastfeeding Friendly (BBF) Toolbox was recently developed to guide
countries in assessing their readiness to and progress with scale-up of
breastfeeding protection, promotion, and support and to develop policy
recommendations to high-level decision makers. Objective: The aim of this study
was to document the BBF process in Mexico, which led to evidence-based
recommendations for policymakers to improve breastfeeding protection, promotion,
and support in the country. Methods: We followed the BBF methodology. First, a
group of experts, with the use of scientific and gray literature, face-to-face
interviews, and their own experience, analyzed and assigned a score to each of
the 8 gears from the BBF index and identified scaling-up gaps on the basis of the
Breastfeeding Gear Model. Then, we developed and presented evidence-based
recommendations to improve breastfeeding protection, promotion, and support.
Results: Mexico's BBF score was 1.4 out of a maximum total of 3 points, which
indicates that there is a low to moderate scaling-up environment to protect,
promote, and support breastfeeding. None of the gears were rated as
"outstanding," and the legislation and policies gear was the only one rated as
strong. Conclusions: The BBF initiative is a useful tool for assessing the
environment for breastfeeding. The Mexican environment for breastfeeding is weak.
On the basis of these results, it is strongly recommended to raise national
awareness on breastfeeding, incorporate the Code of Marketing of Breastmilk
Substitutes in the Mexican legislations, extend maternity leave to 6 mo, and
strengthen evidence-based advocacy and hence the political will that is needed to
secure stable funding and resources for a successful national strategy for the
protection, promotion, and support of breastfeeding in Mexico.
PMID- 29955731
TI - Effect of a High-Protein, High-Fiber Beverage Preload on Subjective Appetite
Ratings and Subsequent Ad Libitum Energy Intake in Overweight Men and Women: A
Randomized, Double-Blind Placebo-Controlled, Crossover Study.
AB - Background: Dietary protein and fiber have been shown to independently improve
subjective measures of appetite control. Objective: The aim of this study was to
determine the acute effects of a high-protein, high-fiber (HP/HFb) beverage taken
as a preload compared with an isocaloric lower-protein, lower-fiber (LP/LFb)
placebo beverage on subjective appetite ratings and subsequent energy intake at
an ad libitum meal in healthy adults. Methods: A total of 50 overweight/obese men
and women [n = 25 men, 25 women; age 30 +/- 2 y; body mass index (BMI) 29.6 +/-
0.3 kg/m2] received a 160 kcal HP/HFb beverage containing 17 g protein and 6 g
fiber on one occasion and an isocaloric LP/LFb placebo beverage containing 1 g
protein and 3 g fiber on another occasion in a randomized, double-blind,
crossover design. Thirty min after consumption of the beverage preload, an ad
libitum pizza meal was provided to be consumed over a 30-min period. Visual
analog scales (VAS) were used to assess subjective appetite ratings throughout
the testing period. The Revised Restraint Scale (RRS) was used to classify
participants as restrained or unrestrained eaters. Results: HP/HFb led to greater
reductions in postprandial desire to eat and hunger compared with LP/LFb (both, P
< 0.05) but did not significantly affect postprandial fullness or prospective
food consumption. Subsequent meal energy intake tended to be lower after HP/HFb
compared with LP/LFb (P = 0.09). A subanalysis showed lower energy intake after
HP/HFb in older participants (>=25 y) compared with LP/LFb, which was not
observed in the younger participants (<25 y). Conclusions: Compared with LP/LFb,
a HP/HFb beverage preload reduced hunger, desire to eat, and tended to reduce
subsequent food intake. Dietary restraint and age appear to influence subsequent
energy intake and should be taken into account when designing nutrition
interventions for weight reduction and/or maintenance. This trial was registered
at clinicaltrials.gov as NCT02979717.
PMID- 29955732
TI - Multi-laboratory validation of a Delta9-tetrahydrocannabinol LC-MS/MS test kit
designed for quantifying THC and marijuana metabolites in blood.
AB - Marijuana legalization has increased the demand for testing of Delta9
tetrahydrocannabinol (THC) and THC metabolites. The THC ToxBox(r) test kit (THC
ToxBox(r)) is commercially available and supports high-throughput LC-MS/MS
analytical methods designed to quantify low levels of THC and THC metabolites in
blood. The purpose of this study is to determine if this new test kit meets the
rigors of laboratory accreditation and produces equivalent results across six
states- and locally-funded laboratories. Each laboratory followed internal method
validation procedures established for their clinical (CLIA) or international
(ISO17025) accreditation program. Test performance indicators included accuracy,
precision, measurement of uncertainty, calibration models, reportable range,
sensitivity, specificity, carryover, interference, ion suppression/enhancement
and analyte stability. Analytes and interferents were resolved within the 6-min
analytical runtime, and the 48-well plate pre-manufactured with calibrators,
second source quality control material, and internal standards at precise
concentrations allowed for simple and consistent sample preparation in less than
one hour. Every laboratory successfully validated test kit procedures for
forensic use. Differences in sensitivity were generally associated with the use
of older equipment. Statistical analysis of results spanning reportable ranges
show that laboratories with different instrument platforms produce equivalent
results at levels sufficiently low enough to support per se limit testing of THC
and THC metabolites (1-5 ng/mL). THC ToxBox(r) represents a viable option for
state- and locally-funded laboratories charged with investigating impaired
driving cases involving marijuana use.
PMID- 29955734
TI - Chaperone-like food components: from basic concepts to food applications.
AB - The significance of chaperones in preventing protein aggregation including
amyloid fibril formation has been extensively documented in the biological field,
but there is limited research on the potential effect of chaperone-like molecules
on food protein functionality and food quality. This review is intended to extend
the potential of chaperone and chaperone-like molecules in the prevention of food
protein aggregation and amyloid fibril formation. The common features of
chaperone molecules responsible for suppressing aggregation and amyloid fibril
formation are firstly presented. Then, the function and applicability of
chaperone and chaperone-like molecules in food products, in particular high
protein beverages where aggregation and fibril formation are undesirable, are
extensively discussed. Protein aggregation in high-protein beverages can be
prevented by chaperone or chaperone-like components, such as caseins, heme
containing proteins, specific peptide fragments, phospholipids and polyphenols.
The diversity of chaperone-like components and mechanisms might provide the
flexibility in taking advantage of their potential applications in different food
products.
PMID- 29955735
TI - Correction: Food-grade monoglyceride oil foams: the effect of tempering on
foamability, foam stability and rheological properties.
AB - Correction for 'Food-grade monoglyceride oil foams: the effect of tempering on
foamability, foam stability and rheological properties' by Robbe Heymans et al.,
Food Funct., 2018, DOI: 10.1039/c8fo00536b.
PMID- 29955733
TI - A Convergent Approach for a Deep Converting Lignin-First Biorefinery Rendering
High-Energy-Density Drop-in Fuels.
AB - Herein, a lignin-centered convergent approach to produce either aliphatic or
aromatic bio-hydrocarbons is introduced. First, poplar or spruce wood was
deconstructed by a lignin-first biorefining process, a technique based on the
early-stage catalytic conversion of lignin, yielding lignin oils along with
cellulosic pulps. Next, the lignin oils were catalytically upgraded in the
presence of a phosphidated Ni/SiO2 catalyst under H2 pressure. Notably,
selectivity toward aliphatics or aromatics can simply be adjusted by changes in
H2 pressure and temperature. The process renders two distinct main cuts of
branched hydrocarbons (gasoline: C6-C10, and kerosene/diesel: C14-C20). As the
approach is H2-intensive, we examined the utilization of pulp as an H2 source via
gasification. For several biomass sources, the H2 obtainable by gasification
stoichiometrically meets the H2 demand of the deep converting lignin-first
biorefinery, making this concept plausible for the production of high-energy
density drop-in biofuels.
PMID- 29955736
TI - X-Ray scattering and physicochemical studies of trialkylamine/carboxylic acid
mixtures: nanoscale structure in pseudoprotic ionic liquids and related
solutions.
AB - We report the results of X-ray scattering, physical, and spectroscopic
measurements on a series of water-saturated trialkylamine/carboxylic acid
mixtures. The results demonstrate the existence of well-defined nanoscale
structures in bulk liquid mixtures at specific acid : amine ratios. These
structures are analogous to those observed in ionic liquids but are driven by the
formation of a hydrogen-bonded network rather than via inter-ion Coulomb forces.
The results of the physical components of this study are closely analogous to
prior observations on anhydrous, low molecular weight acid/amine mixtures, but
this is to our knowledge the first time these observations have been augmented by
the use of X-ray scattering. The results therefore bridge the gap between early
work on amine/acid mixtures and recent studies of protic and pseudoprotic ionic
liquids.
PMID- 29955737
TI - Dynamical resonances in chemical reactions.
AB - The transition state is a key concept in the field of chemistry and is important
in the study of chemical kinetics and reaction dynamics. Chemical reactions in
the gas phase are essentially molecular scattering processes, which are quantum
mechanical in nature. Thus probing and understanding detailed quantum structure
in the transition state region of chemical reactions, such as reactive
resonances, is a central topic in this field. In this article, we focus on recent
progress in the study of resonances in elementary bimolecular reactions using
state-of-the-art transition state spectroscopy methods: high-resolution
photoelectron spectroscopy and quantum state specific backward scattering
spectroscopy. The experimental results are compared with high-level quantum
dynamics calculations based on highly accurate potential energy surfaces. The
dynamics of reactive resonances are also interpreted based on scattering
wavefunctions obtained by time-dependent wavepacket calculations. Here, we review
many systems that illustrate how reactive resonances can strongly influence the
dynamics of elementary chemical reactions.
PMID- 29955738
TI - Dissociative electron attachment induced ring opening in five-membered
heterocyclic compounds.
AB - Five-membered heterocyclic structures, which exist widely in biological systems
and play an active role in various biochemical processes, have been studied
extensively from a fundamental perspective. Here, the fragmentation patterns of
isoxazole, a representative five-membered heterocycle, upon dissociative electron
attachment (DEA) were examined carefully by comparing isoxazole's products with
those of its methylated derivatives. It was found that the most dominant DEA
pathway occurs through the loss of hydrogen at C(3), which leads to ring opening
by O-N bond cleavage at an energy of ~1.5 eV. The ring opening was investigated
further for DEA to other related five-membered ring compounds, i.e., oxazole and
thiazole. The DEA-induced hydrogen loss was much less pronounced or quenched
completely in these two compounds and simultaneous ring-opening behavior was not
detected. This observation is of special interest to applied fields, for example,
the pharmaceutical industry, because several drugs that contain isoxazole
substructures exhibit extensive ring opening during biotransformation.
PMID- 29955739
TI - A dual-analyte probe: hypoxia activated nitric oxide detection with
phototriggered drug release ability.
AB - A new strategy for the detection of hypoxia and NO succeeded by photocontrolled
delivery of an anticancer agent has been demonstrated. The developed system is
able to produce distinct responses (dual channel) upon interaction with hypoxia
and NO. This probe can also release anticancer drugs upon photoirradiation acting
potentially as both a dual-analyte imaging agent and a prodrug.
PMID- 29955740
TI - Effects of substituents on luminescent efficiency of stable triaryl methyl
radicals.
AB - A series of perchlorotriphenyl methyl (PTM) and tris(2,4,6-trichlorophenyl)methyl
(TTM) radical derivatives were synthesized. The factors affecting the
photoluminescence quantum yields (PLQYs) of pi-radicals were studied
systematically for the first time through comparing the photophysical properties
of the synthesized PTM and TTM radicals. The room-temperature PLQY of a PTM
radical derivative achieves to be 56.6%, which is the highest value among the
organic near-infrared materials with peak wavelength over 650 nm. The
photostabilities of the radicals was significantly enhanced via incorporation of
substituent groups. The molecular rigidity, electron donating ability of the
donor and dihedral angle between D-A system were found to be the potential
factors to affect the luminescent efficiency of the open-shell molecules.
PMID- 29955741
TI - Total synthesis and structural revision of an isopanepoxydone analog isolated
from Lentinus strigellus.
AB - Asymmetric total synthesis of compound 1, as a proposed molecular structure of a
natural product, in 11 steps is described. The inconsistency of the
characterization data between our synthesized sample and the natural product
prompted us to propose a different molecular structure as compound 2 and
accordingly accomplish total synthesis in 9 steps and confirm the structural
revision of this natural product. Both total syntheses feature highly regio- and
diastereoselective epoxidation, Stille cross-coupling and cross-metathesis.
PMID- 29955742
TI - Electronic structure and rovibrational predissociation of the 21Pi state in KLi.
AB - Adiabatic potential energy curves of the 31Sigma+, 33Sigma+, 21Pi and 23Pi states
correlating for large internuclear distance with the K(4s) + Li(2p) atomic
asymptote were calculated. Very good agreement between the calculated and the
experimental curve of the 21Pi state allowed for a reliable description of the
dissociation process through a small (~20 cm-1 for J = 0) potential energy
barrier. The barrier supports several rovibrational quasi-bound states and
explicit time evolution of these states via the time-dependent nuclear
Schrodinger equation, showed that the state populations decay exponentially in
time. We were able to precisely describe the time-dependent dissociation process
of several rovibrational levels and found that our calculated spectrum match very
well with the assigned experimental spectrum. Moreover, our approach is able to
predict the positions of previously unassigned lines, particularly in the case of
their low intensity.
PMID- 29955743
TI - Fitting electron density as a physically sound basis for the development of
interatomic potentials of complex alloys.
AB - The development of new interatomic potentials to model metallic systems is a
difficult task, due in part to the dependence between the parameters that
describe the electron density and the short-range interactions. Parameter search
methods are prone to false convergence. To solve this problem, we have developed
a methodology for obtaining the electron density parameters independently of the
short-range interactions, so that physically sound parameters can be obtained to
describe the electron density, after which the short-range parameters can be
fitted, thus reducing the complexity of the process and yielding better
interatomic potentials. With the new method we can develop self-consistent,
accurate force fields, using solely calculations, without the need to fit to
experimental data. Density functional theory calculations are used to compute the
observables with which the potential is fit. We applied the method to a Ni-based
Inconel 625 superalloy (IN625), modelled here as Ni, Cr, Mo and Fe solid solution
alloys. The capability of the force fields developed using this new method is
validated, by comparing the structural and thermo-elastic properties predicted
with the force fields, with the corresponding experimental data, both for single
crystals and polycrystalline alloys.
PMID- 29955744
TI - Preparation of polynuclear NHC complexes by post-synthetic modification of half
sandwich rhodium and iridium complexes bearing C-azolato ligands.
AB - A series of bimetallic and trimetallic complexes has been prepared by N
alkylation of mononuclear half-sandwich rhodium and iridium di-NHC complexes
featuring bidentate chelate ligands composed of a classical NHC and a C-azolato
donor. The shape and the separation between metal centers in the obtained
complexes are highly dependent on the alkylating agent used. While the
polynuclear complexes were formed as diastereomeric mixtures according to NMR
spectroscopy, X-ray diffraction analysis revealed their remarkable preference to
crystallize as meso compounds. The reactivity of the bimetallic, olefin-bridged
complexes in electrophilic addition reactions has been investigated.
PMID- 29955745
TI - An elusive thermal [2 + 2] cycloaddition driven by visible light photocatalysis:
tapping into strain to access C2-symmetric tricyclic rings.
AB - A mild and operationally simple methodology is reported for the synthesis of
cyclobutane rings imbedded within a C2-symmetric tricyclic framework. The method
uses visible light and an iridium-based photocatalyst to drive the oft-stated
"forbidden" thermal [2 + 2] cycloaddition of cycloheptenes and analogs.
Importantly, it generates cyclobutane with four new stereocenters with excellent
stereoselectivity, and perfect regioselectivity. The reaction is propelled
forward when the photocatalyst absorbs a visible light photon, which transfers
this energy to the cycloheptene. Key to success is, upon excitation to the
triplet via sensitization from the photocatalyst, the double bond isomerizes to
give the transient, highly strained, trans-cycloheptene. The trans-cycloheptene
undergoes a strain relieving thermal, intermolecular [pi2s + pi2a] cycloaddition
with another cis-cycloheptene. X-ray analysis reveals that the major product is
the head-to-head, C2-symmetric all trans-cyclobutane. Additionally, a dramatic
display structural complexity enhancement is observed with the use of chiral
cycloheptenols possessing one stereocenter, which results in the formation of
cyclobutanes with six contiguous stereocenters with good to excellent
diastereocontrol, and can be used to isolate single stereoisomers of
stereochemically complex cyclobutanes in good yield.
PMID- 29955746
TI - K2TeP2O8: a new telluro-phosphate with a pentagonal Te-P-O layer structure.
AB - A new telluro-phosphate K2TeP2O8 was synthesized by a high temperature solution
method. It crystallizes in the orthorhombic space group P21212 and features a
[TeP2O8]2- layer structure, which is the first layer structure built by Te-O and
P-O groups among the telluro-phosphates. More interestingly, the layer structure
in K2TeP2O8 is nearly pentagonal. First-principles theoretical calculations
suggest that K2TeP2O8 possesses a large birefringence compared to phosphates.
Furthermore, IR spectra, UV-vis-NIR diffuse reflectance spectroscopy data,
thermal behavior, and electronic structure calculations were studied.
PMID- 29955747
TI - Increased intake of vitamin B12, folate, and omega-3 fatty acids to improve
cognitive performance in offspring born to rats with induced hypertension during
pregnancy.
AB - Vitamin B12, folic acid, and docosahexaenoic acid levels are reported to be
altered in women with preeclampsia. This study examined the effect of the above
nutrients on brain neurotrophins and on the cognitive performance in adult
offspring in a pregnancy-induced hypertension rat model. Pregnant dams were
assigned to control, PIH-induced, and PIH-induced supplemented with vitamin B12,
folate, omega-3 fatty acids, and the combined supplementation of vitamin B12,
folate, and omega-3 fatty acids groups. In the PIH group, brain-derived
neurotrophic factor levels (BDNF) were lower in the offspring at birth, while the
adult offspring showed lower levels of docosahexaenoic acid (DHA) in the
hippocampus and BDNF (p < 0.05 for both) in the cortex as compared to in the
control group. They also demonstrated higher (p < 0.05) escape latency in the
Morris water maze test and performed a greater (p < 0.01 for all) number of
errors in the Radial eight-arm maze test. A combined supplementation of vitamin
B12, folic acid, and omega-3 fatty acids improved the levels of LCPUFA,
neurotrophins, and cognition. A maternal diet consisting of high levels of
folate, vitamin B12, and DHA reduced the risk for cognitive disorders in the
adult offspring in an animal model of pregnancy-induced hypertension.
PMID- 29955748
TI - Pseudorotaxanes in the gas phase: structure and energetics of protonated
dibenzylamine-crown ether complexes.
AB - We observe UV spectra of protonated dibenzylamine (dBAMH+) and its complexes with
15-crown-5 (dBAMH+-15C5), 18-crown-6 (dBAMH+-18C6), and 24-crown-8 (dBAMH+-24C8)
under cold (~10 K) gas-phase conditions by UV photodissociation (UVPD) and UV-UV
hole-burning (HB) spectroscopy. The UVPD spectrum of the dBAMH+-15C5 complex
shows an extensive low-frequency progression, which originates from a unique
conformation of the dBAMH+ part with benzene rings facing closely to each other,
while UVPD and calculation results suggest open conformations of the dBAMH+ part
for dBAMH+-18C6 and dBAMH+-24C8. UV-UV HB spectra of the dBAMH+-24C8 complex
indicate that there exist at least two conformers; multiple conformations can
contribute to high stability of dBAMH+-24C8 pseudorotaxane due to
"conformational" entropic effects. The UVPD experiment indicates that the
dissociation probability of dBAMH+-24C8 into dBAMH+ and 24C8 is substantially
smaller than that of dBAMH+-15C5 and dBAMH+-18C6, which can be related to the
barrier height in the dissociation process. The energetics of the dBAMH+-24C8
complex is investigated experimentally with NMR spectroscopy and theoretically
with the global reaction route mapping (GRRM) method. An energy barrier of ~60 kJ
mol-1 is present in the pseudorotaxane formation in solution, whereas there is no
barrier in the gas phase. In the course of the photodissociation, excited dBAMH+
24C8 complexes can be trapped at many local minima corresponding to multiple
conformations. This can result in effective dissipation of internal energy into
degrees of freedom not correlated to the dissociation and decrease the
dissociation probability for the dBAMH+-24C8 complex in the gas phase. The energy
barrier for the pseudorotaxane formation in solution originates not simply from
the slippage process but rather from solvent effects on the dBAMH+-24C8 complex.
PMID- 29955749
TI - Different scenarios of dynamic coupling in glassy colloidal mixtures.
AB - Colloidal mixtures represent a versatile model system to study transport in
complex environments. They allow for a systematic variation of the control
parameters, namely size ratio, total volume fraction and composition. We study
the effects of these parameters on the dynamics of dense suspensions using
molecular dynamics simulations and differential dynamic microscopy experiments.
We investigate the motion of small particles through the matrix of large
particles as well as the motion of large particles. A particular focus is on the
coupling of the collective dynamics of small and large particles and on the
different mechanisms leading to this coupling. For large size ratios, of about 1
: 5, and an increasing fraction of small particles, the dynamics of the two
species become increasingly coupled and reflect the structure of the large
particles. This is attributed to the dominant effect of the large particles on
the motion of the small particles, which is mediated by the increasing crowding
of the small particles. Furthermore, for moderate size ratios of about 1 : 3 and
sufficiently high fractions of small particles, mixed cages are formed and hence
the dynamics are also strongly coupled. Again, the coupling becomes weaker as the
fraction of small particles is decreased. In this case, however, the collective
intermediate scattering function of the small particles shows a logarithmic decay
corresponding to a broad range of relaxation times.
PMID- 29955750
TI - Controllable transformation between 3D and 2D perovskites through cation
exchange.
AB - A facile post-synthesis cation exchange approach has been employed to
controllably tune the optical and structural properties of colloidal perovskite
nanocrystals (NCs). These optical changes are attributed to the structural
transformation of perovskite NCs from three-dimensional (3D) to two-dimensional
(2D) layered crystalline forms and vice versa.
PMID- 29955751
TI - Size and crystallinity control of two-dimensional porous cobalt oxalate thin
sheets: tuning surface structure with enhanced performance for aqueous asymmetric
supercapacitors.
AB - With excellent layered structures, abundant pores and a high specific surface
area, two-dimensional (2D) porous nanostructured materials have been demonstrated
to show great potential in supercapacitors. At present, it is highly desirable
but remains challenging to prepare different sizes and crystallinity of 2D porous
thin sheets so as to further improve the performance of supercapacitors. Herein,
2D porous cobalt-oxalate (Co-OA) thin sheets with different sizes and
crystallinity assembled by interconnected nanosheet array frameworks have been
successfully synthesized, using cobalt nitrate hexahydrate as a cobalt source and
oxalic acid dihydrate as a ligand, through a simple hydrothermal strategy at 220
degrees C for different reaction times. The as-prepared sample at 220 degrees C
for 20 h, has a high area specific capacitance (1.631 F cm-2 at the current
density of 1.2 mA cm-2), good rate capability (80.6% retention upon increasing
the current density from 1.2 to 12 mA cm-2) and excellent cycling performance
(1.5% attenuation at 6.0 mA cm-2 for 2000 cycles). In addition, one aqueous
asymmetric supercapacitor (ASC) is constructed based on the sample synthesised at
220 degrees C for 20 h as positive electrodes and activated carbon (AC) as
negative electrodes. This ASC effectively provides a maximum energy density of
17.675 Wh kg-1 at 900 W kg-1, still maintaining 8.25 Wh kg-1 at 9000 W kg-1,
which demonstrates it may be a promising candidate in energy storage for
supercapacitors. It is worth emphasizing that this strategy could be extended to
fabricate other materials with different sizes and crystallinity.
PMID- 29955752
TI - Origins of possible synergistic effects in the interactions between metal atoms
and MoS2/graphene heterostructures for battery applications.
AB - The interactions between metals and two-dimensional materials, in particular, the
adsorption energies, strongly determine the performances of rechargeable
batteries. Previously, it has been demonstrated that heterostructures of two
dimensional (2D) materials can lead to enhanced metal adsorptions, which were
ascribed to the existence of 'synergistic' effects amongst metal atoms and two
different 2D materials. However, further investigations are still required to
reveal the physical mechanisms behind the contribution of these possible
'synergistic' effects for metal intercalations in 2D heterostructures. Here, we
selected MoS2/graphene as a prototypical system, and we examined the adsorption
and intercalation thermochemistry of monovalent atoms (Li, Na and K) and
multivalent atoms (Mg, Ca and Al) using density-functional theory (DFT)
calculations. The synergistic effects arising from charge polarizations in these
systems were quantified using the three-body interaction energy terms. Our
results show strong system dependencies whereby the interactions between the Mg
or Ca atom with the MoS2/graphene heterostructures might exhibit cooperative
bindings. Nevertheless, metal adsorptions on top of the graphene surface were all
found to be anti-cooperative in this case. Our results suggest that enhancement
of metal adsorptions using 2D heterostructures is predominantly driven by
increasing dispersion interactions due to increases in the interaction surface
areas.
PMID- 29955753
TI - Spontaneous separation of on-surface synthesized tris-helicenes into two
dimensional homochiral domains.
AB - The on-surface Ullmann coupling of 2,3-dibromo[4]helicene molecules is studied on
Au(111) and Cu(111) surfaces. Bis-helicene and tris-helicene are identified with
scanning tunnelling microscopy and X-ray photoelectron spectroscopy as reaction
products. The produced star-shaped tris-helicenes self-assemble on Au(111)
spontaneously into large homochiral domains.
PMID- 29955754
TI - A fluorometric skin-interfaced microfluidic device and smartphone imaging module
for in situ quantitative analysis of sweat chemistry.
AB - The rich composition of solutes and metabolites in sweat and its relative ease of
collection upon excretion from skin pores make this class of biofluid an
attractive candidate for point of care analysis. Wearable technologies that
combine electrochemical sensors with conventional or emerging semiconductor
device technologies offer valuable capabilities in sweat sensing, but they are
limited to assays that support amperometric, potentiometric, and colorimetric
analyses. Here, we present a complementary approach that exploits fluorometric
sensing modalities integrated into a soft, skin-interfaced microfluidic system
which, when paired with a simple smartphone-based imaging module, allows for in
situ measurement of important biomarkers in sweat. A network array of
microchannels and a collection of microreservoirs pre-filled with fluorescent
probes that selectively react with target analytes in sweat (e.g. probes), enable
quantitative, rapid analysis. Field studies on human subjects demonstrate the
ability to measure the concentrations of chloride, sodium and zinc in sweat, with
accuracy that matches that of conventional laboratory techniques. The results
highlight the versatility of advanced fluorescent-based imaging modalities in
body-worn sweat microfluidics platforms, and they suggest some practical
potential for these ideas.
PMID- 29955755
TI - Decision Tree Model vs Traditional Measures to Identify Patterns of Sun
Protective Behaviors and Sun Sensitivity Associated With Sunburn.
AB - Importance: Understanding patterns of sun-protective behaviors and their
association with sunburn can provide important insight into measurement
approaches and intervention targets. Objective: To assess whether decision-based
modeling can be used to identify patterns of sun-protective behaviors associated
with the likelihood of sunburn and to compare the predictive value of this method
with traditional (ie, composite score) measurement approaches. Design, Setting,
and Participants: This cross-sectional study used a nationally representative
sample of 31 162 US adults from the 2015 National Health Interview Survey,
consisting of household interviews conducted in person and completed by telephone
when necessary. Participants included civilian noninstitutionalized US adults.
Data were collected from January 1 through December 31, 2015. Main Outcomes and
Measures: The associations among sun sensitivity, multiple sun-protective
behaviors (ie, using sunscreen, seeking shade, wearing a hat, and wearing
protective clothing), and sunburn were examined using a chi2 automatic
interaction detection method for decision tree analysis. Results were compared
with a composite score approach. Results: In our study population of 28 558
respondents with complete data (54.1% women; mean [SD] age, 49.0 [18.0] years),
20 patterns of sun protection were identified. Among 15 992 sun-sensitive
individuals, those who used only sunscreen had the highest likelihood of sunburn
(62.4%). The group with the lowest likelihood of sunburn did not report using
sunscreen but engaged in the other 3 protective behaviors (24.3% likelihood of
sunburn). Among 12 566 non-sun-sensitive individuals, those who engaged in all 4
protective behaviors had the lowest likelihood of sunburn (6.6%). The highest
likelihood of sunburn was among those who only reported sunscreen use (26.2%).
The decision tree model and the composite score approach correctly classified a
similar number of cases; however, the decision tree model was superior in
classifying cases with sunburn (44.3% correctly classified in the decision tree
vs 25.9% with the composite score). Conclusions and Relevance: This innovative
application of a decision tree analytic approach demonstrates the interactive and
sometimes counterintuitive effects of multiple sun-protective behaviors on
likelihood of sunburn. These data show where traditional measurement approaches
of behavior may fall short and highlight the importance of linking behavior to a
clinically relevant outcome. Given the scope of those affected and enormous
associated health care costs, improving efforts in skin cancer prevention has the
potential for a significant effect on public health.
PMID- 29955756
TI - Association of Heparin-Induced Thrombocytopenia With Bacterial Infection in
Trauma Patients.
PMID- 29955757
TI - Clinical and Laboratory Markers Associated With Relapse in Cutaneous
Polyarteritis Nodosa.
AB - Importance: In cutaneous polyarteritis nodosa (CPAN), less aggressive treatments
can be selected, because CPAN is not associated with life-threatening or
progressive outcomes. Although patients with a recurrent clinical course may
require additional immunosuppressive therapies, no pretreatment factors
associated with a worse prognosis in CPAN have been reported. Objective: To
identify clinical or laboratory markers associated with relapse of CPAN. Design,
Setting, and Participants: This retrospective case series was performed at a
dermatology clinic of a tertiary referral center in Okayama, Japan, from October
1, 2001, through April 30, 2017. Of 30 patients identified with CPAN, the 21 with
histopathologic evidence of disease were eligible and enrolled in the study. Main
Outcomes and Measures: The medical database was examined for sex, age at
diagnosis, affected anatomical sites, type and extent of skin lesion, laboratory
data, initial therapies, duration of follow-up, and current status. Relapse was
defined as the first reoccurrence or new onset of cutaneous disease that required
further escalation of treatment with prednisolone at a dosage of greater than 20
mg/d and/or add-on use of immunosuppressant therapy, more than 6 months after
initial treatment. The pretreatment factors were statistically evaluated between
the groups without and with relapse. Results: The 21 patients included 5 males
and 16 females with a median age of 49 years (range, 11-74 years) at diagnosis.
The median follow-up was 42 months (range, 8-374 months). Pretreatment cutaneous
ulcer was significantly associated with relapse between the 2 groups (0 of 11 in
the nonrelapse group vs 4 of 10 in the relapse group; chi21 = 4.67; P < .05). In
the laboratory test results, significantly higher mean (SD) values were observed
in the relapse group for C-reactive protein level (0.23 [2.00] vs 6.03 [3.10]
mg/dL; standard error of the mean [SEM], 3.40 mg/dL; 95% CI, 0.01-10.8 mg/dL; P =
.01), absolute neutrophil count (ANC) (3.4 * 103/MUL [1.1 * 103/MUL] vs 6.0 *
103/MUL [3.2 * 103/MUL]; SEM, 2.9 * 103/MUL; 95% CI, 1.9 * 103/MUL to 14.6 *
103/MUL; P = .001), neutrophil-to-lymphocyte ratio (1.4 [0.8] vs 2.8 [0.9]; SEM,
1.2; 95% CI, 1.1-4.9; P = .002), and systemic immune-inflammation index (5.1 *
105 [3.9 * 105] vs 11.7 * 105 [7.7 * 105]; SEM, 7.3 * 105; 95% CI, 3.3 * 105 to
31.1 * 105; P = .007). The estimated 2-year cumulative relapse rate was
significantly high in the patients with blood ANC of greater than 4.9 * 103/MUL
compared with 4.9 * 103/MUL or less (9 of 10 [90%] vs 2 of 11 [18%]; 95% CI, 6%
72%). Conclusions and Relevance: Pretreatment status of cutaneous ulcer, the
serum C-reactive protein level, the blood ANC, the neutrophil-to-lymphocyte
ratio, and the systemic immune-inflammation index are associated with a worse
prognosis in CPAN.
PMID- 29955758
TI - Bladder Extirpation vs Preservation: The Treatment Debate.
PMID- 29955759
TI - The Pathogenesis of Choanal Atresia.
PMID- 29955760
TI - Continued Poor Survival in Metastatic Uveal Melanoma: Implications for Molecular
Prognostication, Surveillance Imaging, Adjuvant Therapy, and Clinical Trials.
PMID- 29955761
TI - Right Lower Quadrant Pain With Melena.
PMID- 29955762
TI - The Cognitive Reserve Should Be Controlled When Using Neuroimaging to Assess
Relapse in Major Depressive Disorder-Reply.
PMID- 29955763
TI - A Middle-aged Woman With Vision Loss and Cecocentral Scotoma.
PMID- 29955765
TI - Age and Treatment of Nonmelanoma Skin Cancer.
PMID- 29955764
TI - A Network-based Zoning for Parallel Whole-Cell Simulation.
AB - Motivation: In Computational Cell Biology, whole-cell modeling and simulation is
an absolute requirement to analyze and explore the cell of an organism. Despite
few individual efforts on modeling, the prime obstacle hindering its development
and progress is its compute-intensive nature. Towards this end, little knowledge
is available on how to reduce the enormous computational overhead and which
computational systems will be of use. Results: In this article, we present a
network-based zoning approach that could potentially be utilized in the
parallelization of whole-cell simulations. Firstly, we construct the protein
protein interaction graph of the whole-cell of an organism using experimental
data from various sources. Based on protein interaction information, we predict
protein locality and allocate confidence score to the interactions accordingly.
We then identify the modules of strictly localized interacting proteins by
performing interaction graph clustering based on the confidence score of the
interactions. By applying this method to Escherichia coli K12, we identified 188
spatially localized clusters. After a thorough Gene Ontology-based analysis, we
proved that the clusters are also in functional proximity. We then conducted
Principal Coordinates Analysis to predict the spatial distribution of the
clusters in the simulation space. Our automated computational techniques can
partition the entire simulation space (cell) into simulation sub-cells. Each of
these sub-cells can be simulated on separate computing units of the High
Performance Computing (HPC) systems. We benchmarked our method using proteins.
However, our method can be extended easily to add other cellular components like
DNA, RNA, and metabolites. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29955766
TI - Cutavirus Infection in Primary Cutaneous B- and T-Cell Lymphoma.
PMID- 29955767
TI - Orchid colonization: multiple parallel dispersal events and mosaic genetic
structure in Dactylorhiza majalis ssp. lapponica on the Baltic island of Gotland.
AB - Background and Aims: The island of Gotland in the Baltic Sea has had no contact
with surrounding continental areas since the withdrawal of the Weichselian ice
sheet at approx. 17 ka BP. Plants present on Gotland must have arrived by long
distance dispersal, so populations are expected to exhibit reduced levels of
genetic diversity compared with populations on surrounding mainlands. However,
orchids have very small seeds, which appear well adapted to long-distance
dispersal, and they should therefore be less affected than other plant species by
colonization bottlenecks. The aim of this study was to analyse the genetic
structure of orchids colonizing isolated islands, using the marsh orchid
Dactylorhiza majalis ssp. lapponica as a case study. Methods: More than 500
samples from 27 populations were analysed for 15 plastid and eight nuclear marker
loci. Population diversity and differentiation patterns were compared for nuclear
and plastid marker systems and analysed in relation to geographical location. Key
Results: We found high genetic diversity but no clear geographical structure of
genetic differentiation between populations on Gotland. However, the between
population differentiation in plastid and nuclear markers were correlated and the
greatest diversity was found at sites at comparatively high elevations, which
were the first to emerge above the water after the Ice Age. Conclusions: The
regional population on Gotland has been established by a minimum of four
dispersal events from continental regions. Subsequent gene flow between sites has
not yet homogenized the differentiation pattern originating from initial
colonization. We conclude that long-distance seed dispersal in orchids has a
strong impact on structuring genetic diversity during periods of expansion and
colonization, but contributes less to gene flow between populations once a stable
population structure has been achieved.
PMID- 29955768
TI - Targeting Tropomyosin Receptor Kinase in Cutaneous CYLD Defective Tumors With
Pegcantratinib: The TRAC Randomized Clinical Trial.
AB - Importance: There are no medical interventions for the orphan disease CYLD
cutaneous syndrome (CCS). Transcriptomic profiling of CCS skin tumors previously
highlighted tropomyosin receptor kinases (TRKs) as candidate therapeutic targets.
Objective: To investigate if topical targeting of TRK with an existing topical
TRK inhibitor, pegcantratinib, 0.5% (wt/wt), is safe and efficacious in CCS.
Design, Setting, and Participants: A phase 1b open-label safety study, followed
by a phase 2a within-patient randomized (by tumor), double-blind, placebo
controlled trial (the Tropomyosin Receptor Antagonism in Cylindromatosis [TRAC]
trial). The setting was a single-center trial based at a tertiary dermatogenetics
referral center for CCS (Royal Victoria Infirmary, Newcastle, United Kingdom).
Patients who had germline mutations in CYLD or who satisfied clinical diagnostic
criteria for CCS were recruited between March 1, 2015, and July 1, 2016.
Interventions: In phase 1b, patients with CCS applied pegcantratinib for 4 weeks
to a single skin tumor. In phase 2a, allocation of tumors was to either receive
active treatment on the right side and placebo on the left side (arm A) or active
treatment on the left side and placebo on the right side (arm B). Patients were
eligible if they had 10 small skin tumors, with 5 matched lesions on each body
side; patients were randomized to receive active treatment (pegcantratinib) to
one body side and placebo to the other side once daily for 12 weeks. Main
Outcomes and Measures: The primary outcome measure was the number of tumors
meeting the criteria for response in a prespecified critical number of
pegcantratinib-treated tumors. Secondary clinical outcome measures included an
assessment for safety of application, pain in early tumors, and compliance with
the trial protocol. Results: In phase 1b, 8 female patients with a median age of
60 years (age range, 41-80 years) were recruited and completed the study. None of
the participants experienced any adverse treatment site reactions. Three patients
reported reduced pain in treated tumors. In phase 2a (15 patients [13 female;
median age, 51 years], with 150 tumors), 2 tumors treated with pegcantratinib
achieved the primary outcome measure of response compared with 6 tumors treated
with placebo. The primary prespecified number of responses was not met. The
incidence of adverse events was low. Conclusions and Relevance: In this study,
pegcantratinib, 0.5% (wt/wt), applied once daily appeared to be well tolerated
and to penetrate the tumor tissue; however, the low tumor drug concentrations
demonstrated are likely to account for the lack of response. Dose-escalation
studies to assess the maximal tolerated dose may be beneficial in future studies
of CCS. Trial Registration: isrctn.org Identifier: ISRCTN75715723.
PMID- 29955770
TI - Hybrid correction of highly noisy long reads using a variable-order de Bruijn
graph.
AB - Motivation: The recent rise of long read sequencing technologies such as Pacific
Biosciences and Oxford Nanopore allows to solve assembly problems for larger and
more complex genomes than what allowed short reads technologies. However, these
long reads are very noisy, reaching an error rate of around 10 to 15% for Pacific
Biosciences, and up to 30% for Oxford Nanopore. The error correction problem has
been tackled by either self-correcting the long reads, or using complementary
short reads in a hybrid approach. However, even though sequencing technologies
promise to lower the error rate of the long reads below 10%, it is still higher
in practice, and correcting such noisy long reads remains an issue. Results: We
present HG-CoLoR, a hybrid error correction method that focuses on a seed-and
extend approach based on the alignment of the short reads to the long reads,
followed by the traversal of a variable-order de Bruijn graph, built from the
short reads. Our experiments show that HG-CoLoR manages to efficiently correct
highly noisy long reads that display an error rate as high as 44%. When compared
to other state-of-the-art long read error correction methods, our experiments
also show that HG-CoLoR provides the best trade-off between runtime and quality
of the results, and is the only method able to efficiently scale to eukaryotic
genomes. Availability and implementation: HG-CoLoR is implemented is C++,
supported on Linux platforms and freely available at
https://github.com/morispi/HG-CoLoR. Supplementary information: Supplementary
data are available at Bioinformatics online.
PMID- 29955769
TI - Cardiovascular Risk Factors, Depression, and Alcohol Consumption During
Joblessness and During Recessions Among Young Adults in CARDIA.
AB - Research has shown that recessions are associated with lower cardiovascular
mortality, but unemployed individuals have a higher risk of cardiovascular
disease (CVD) or death. We used data from 8 consecutive examinations (1985-2011)
of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, modeled
in fixed-effect panel regressions, to investigate simultaneously the associations
of CVD risk factors with the employment status of individuals and the
macroeconomic conditions prevalent in the state where the individual lives. We
found that unemployed individuals had lower levels of blood pressure, high
density lipoprotein cholesterol, and physical activity, and they had
significantly higher depression scores, but they were similar to their
counterparts in smoking status, alcohol consumption, low-density lipoprotein
cholesterol levels, body mass index, and waist circumference. A 1-percentage
point higher unemployment rate at the state level was associated with lower
systolic (-0.41 mm Hg, 95% CI: -0.65, -0.17) and diastolic (-0.19, 95% CI: -0.39,
0.01) blood pressure, higher physical activity levels, higher depressive symptom
scores, lower waist circumference, and less smoking. We conclude that levels of
CVD risk factors tend to improve during recessions, but mental health tends to
deteriorate. Unemployed individuals are significantly more depressed, and they
likely have lower levels of physical activity and high-density lipoprotein
cholesterol.
PMID- 29955771
TI - Aerosol Dispersal Patterns and Resulting Effects on Tribolium confusum
(Coleoptera: Tenebrionidae) Adults.
AB - Aerosol application of insecticides as part of an integrated pest management
program is becoming more widely adopted in food facilities such as flour mills.
However, the method of application and the complex structural features within a
facility can impact how insecticide particles travel and settle on surfaces and
therefore impact the consistency in efficacy obtained. Here we investigated how
the location from which an aerosol insecticide is released impacts the spatial
pattern of aerosol deposition, using efficacy against Tribolium confusum
Jacquelin du Val (Coleoptera: Tenebrionidae), the confused flour beetle, as a
model insects. Concrete bioassay arenas containing T. confusum adults and flour
were exposed to two commercial aerosol formulations, pyrethrin + pyriproxyfen and
pyrethrin + methoprene, and observed for initial adult knockdown and subsequent
mortality. Aerosols were applied from one of three static locations or a fourth
application comprised of multiple aerosol release points. The aerosol release
position had a significant effect on T. confusum adult knockdown and mortality;
both ranged from 0 to 100% depending on bioassay arena location. The multiple
aerosol release positions tended to have more bioassay arenas with higher
knockdown and mortality, and had a more consistent impact across all arena
locations, yet there were still areas on the mill floor where little adult beetle
efficacy was observed. The effect of each aerosol on T. confusum adults is a
culmination of how the aerosol was applied, the distance the aerosol particles
traveled, and the complexity of a milling facility.
PMID- 29955772
TI - Strengthening the Case for the Role of Thrombophilia in Calciphylaxis.
PMID- 29955773
TI - Age and Treatment of Nonmelanoma Skin Cancer.
PMID- 29955774
TI - Database Selection and Heterogeneity-More Details, More Credibility.
PMID- 29955775
TI - Benefits and Harms of the Centers for Medicare & Medicaid Services Ruling on Next
Generation Sequencing.
PMID- 29955776
TI - Nuclear Circulating Tumor Cell Androgen Receptor Variant 7 in Castration
Resistant Prostate Cancer: The Devil Is in the Detail.
PMID- 29955777
TI - Age and Treatment of Nonmelanoma Skin Cancer.
PMID- 29955778
TI - The Objective of Local Therapy in Oligometastatic Cancer Is a Moving Target.
PMID- 29955779
TI - Treating the Eyes to Help the Brain: The Association Between Visual and Cognitive
Function.
PMID- 29955780
TI - Comparing Survival Outcomes and Costs Associated With Radical Cystectomy and
Trimodal Therapy for Older Adults With Muscle-Invasive Bladder Cancer.
AB - Importance: Radical cystectomy is the guidelines-recommended treatment of muscle
invasive bladder cancer, but a resurgence of trimodal therapy has occurred.
Limited comparative data are available on outcomes and costs attributable to
these 2 treatments. Objective: To compare the survival outcomes and costs between
trimodal therapy and radical cystectomy in older adults with muscle-invasive
bladder cancer. Design, Setting, and Participants: This population-based cohort
study used data from the Surveillance, Epidemiology, and End Results-Medicare
linked database. A total of 3200 older adults (aged >=66 years) with clinical
stage T2 to T4a bladder cancer diagnosed from January 1, 2002, to December 31,
2011, and with claims data available through December 31, 2013, were included in
the analysis. Patients who received radical cystectomy underwent either only
surgery or surgery in combination with radiotherapy or chemotherapy. Patients who
received trimodal therapy underwent transurethral resection of the bladder
followed by radiotherapy and chemotherapy. Propensity score matching by
sociodemographic and clinical characteristics was used. Data analysis was
performed from August 1, 2017, to March 11, 2018. Main Outcomes and Measures:
Overall survival and cancer-specific survival were evaluated using the Cox
proportional hazards regression model and the Fine and Gray competing risk model.
All Medicare health care costs for inpatient, outpatient, and physician services
within 30, 90, and 180 days of treatment were compared. The total amount spent
nationwide was estimated, using 180-day medical costs between treatments, by the
total number of new cases of muscle-invasive bladder cancer in the United States
in 2011. Results: Of the 3200 patients who met the inclusion criteria, 2048
(64.0%) were men and 1152 (36.0%) were women, with a mean (SD) age of 75.8 (6.0)
years. After propensity score matching, 687 patients (21.5%) underwent trimodal
therapy and 687 patients (21.5%) underwent radical cystectomy. Patients who
underwent trimodal therapy had significantly decreased overall survival (hazard
ratio [HR], 1.49; 95% CI, 1.31-1.69) and cancer-specific survival (HR, 1.55; 95%
CI, 1.32-1.83). No differences in costs at 30 days were observed between trimodal
therapy ($15 233 in 2002 vs $18 743 in 2011) and radical cystectomy ($17 990 in
2002 vs $21 738 in 2011). However, median total costs were significantly higher
with trimodal therapy than with radical cystectomy at 90 days ($80 174 vs $69
181; median difference, $8964; Hodges-Lehmann 95% CI, $3848-$14 079) and at 180
days ($179 891 vs $107 017; median difference, $63 771; Hodges-Lehmann 95% CI,
$55 512-$72 029). Extrapolating these figures to the total US population revealed
$335 million in excess spending for trimodal therapy compared with the less
costly radical cystectomy ($492 million) for patients who received a muscle
invasive bladder cancer diagnosis in 2011. Conclusions and Relevance: Trimodal
therapy was associated with significantly decreased overall survival and cancer
specific survival as well as $335 million in excess spending in 2011. These
findings have important health policy implications regarding the appropriate use
of high value-based care among older adults with invasive bladder cancer who are
candidates for either radical cystectomy or trimodal therapy.
PMID- 29955781
TI - Association of Midlife Cardiorespiratory Fitness With Incident Depression and
Cardiovascular Death After Depression in Later Life.
AB - Importance: Cardiorespiratory fitness (hereinafter referred to as fitness) as
estimated by exercise testing is a modifiable risk factor independently
associated with chronic diseases, cardiovascular disease (CVD) events, and
mortality, but the association of fitness at midlife with incidence of later-life
depression and the risk of CVD mortality after a depression diagnosis is unknown.
Objective: To determine whether fitness measured in midlife would be inversely
associated with later-life CVD mortality with antecedent depression. Design,
Setting, and Participants: This retrospective cohort study at a single-center,
community-based preventive medicine clinic was performed as part of the Cooper
Center Longitudinal Study. Data were collected from January 13, 1971, through
December 31, 2009, and analyzed from October 6, 2015, through August 14, 2017.
Participants included generally healthy men and women who presented for
preventive medicine examinations at midlife and who were eligible for Medicare
from 1999 to 2010. Those with a self-reported history of depression, myocardial
infarction, or stroke at examination were excluded. Exposures: Objective midlife
fitness estimated from results of treadmill exercise testing. Main Outcomes and
Measures: Depression diagnosis from Medicare claims files using established
algorithms and CVD mortality from National Death Index records. Results: A total
of 17 989 participants (80.2% men) with a mean (SD) age of 50.0 (8.7) years were
included. After 117 218 person-years of Medicare follow-up, 2701 depression
diagnoses, 610 deaths due to CVD without prior depression, and 231 deaths due to
CVD after depression were observed. A high level of fitness in midlife was
associated with a 16% lower risk of depression (hazard ratio [HR], 0.84; 95% CI,
0.74-0.95) compared with a low level of fitness. A high fitness level was also
associated with a 61% lower risk of death due to CVD without depression (HR,
0.39; 95% CI, 0.31-0.48) compared with a low level of fitness. After a diagnosis
of depression, a high fitness level was associated with a 56% lower risk of death
due to CVD (HR, 0.44; 95% CI, 0.31-0.64) compared with a low fitness level.
Conclusions and Relevance: Midlife fitness is associated with a lower risk of
later-life depression, CVD mortality, and CVD mortality after incident later-life
depression. These findings suggest the importance of midlife fitness in primary
prevention of depression and subsequent CVD mortality in older age and should
encourage physicians to consider fitness and physical activity in promoting
healthy aging.
PMID- 29955782
TI - Perceived Facial Distortions in Selfies Are Explained by Viewing Habits-Reply.
PMID- 29955783
TI - Intraoperative Measurement of the Anatomic Features of the Lower Lateral
Cartilage and Nasal Tip Shape of the Asian Nose.
PMID- 29955784
TI - Transitions in JAMA Psychiatry.
PMID- 29955785
TI - Age-related decline in antibiotic prescribing for uncomplicated respiratory tract
infections in primary care in England following the introduction of a national
financial incentive (the Quality Premium) for health commissioners to reduce use
of antibiotics in the community: an interrupted time series analysis.
AB - Objectives: To assess the impact of the 2015/16 NHS England Quality Premium
(which provided a financial incentive for Clinical Commissioning Groups to reduce
antibiotic prescribing in primary care) on antibiotic prescribing by General
Practitioners (GPs) for respiratory tract infections (RTIs). Methods: Interrupted
time series analysis using monthly patient-level consultation and prescribing
data obtained from the Clinical Practice Research Datalink (CPRD) between April
2011 and March 2017. The study population comprised patients consulting a GP who
were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in
patients (both aggregate and stratified by age) with a recorded diagnosis of
uncomplicated RTI, before and after the implementation of the Quality Premium.
Results: Prescribing rates decreased over the 6 year study period, with evident
seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing
(equating to 14.65 prescriptions per 1000 RTI consultations) (P < 0.05) in April
2015, coinciding with the introduction of the Quality Premium. This reduction was
sustained, such that after 2 years there was a 3% decrease in prescribing
relative to that expected had the pre-intervention trend continued. There was
also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic
prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the
greatest decline with a 6% relative change 2 years after the intervention. Of the
RTI indications studied, the greatest reductions in antibiotic prescribing were
seen for patients with sore throats. Conclusions: Community prescribing of
antibiotics for RTIs significantly decreased following the introduction of the
Quality Premium, with the greatest reduction seen in younger patients.
PMID- 29955786
TI - Association of the Video Head Impulse Test With Improvement of Dynamic Balance
and Fall Risk in Patients With Dizziness.
AB - Importance: It is important to know whether recovery of the vestibuloocular
reflex (VOR) as measured by the video head impulse test (vHIT) is associated with
the recovery of dynamic balance. It is also critical to know how much change in
VOR gain is clinically relevant for establishing the recovery of dynamic balance.
Objectives: To investigate the association between improved VOR gain as measured
by the vHIT and improved dynamic balance (reduced fall risk) as measured by the
dynamic gait index (DGI) and to calculate the minimal clinically important
difference of VOR gain. Design, Setting, and Participants: This retrospective
case series study was performed at a tertiary referral center at the Johns
Hopkins University School of Medicine. Thirty-eight consecutive patients with
subacute or chronic dizziness from January 1, 2014, through May 31, 2017, who
visited the vestibular physical therapy clinic were included in the study.
Interventions: Each patient was evaluated with room light and video-infrared
oculomotor examination, vHIT, and balance testing before and after vestibular
physical therapy. Main Outcomes and Measures: Gain of the lesioned VOR and score
on the DGI. Results: Among the 38 patients (25 women [66%]; mean [SD] age, 65
[14] years), the mean (SD) initial lesioned VOR gain was 0.66 (0.23) and initial
DGI score was 16 (3). No correlation was found between initial VOR gain and
initial DGI score (r = -0.04; 95% CI, -0.35 to 0.28). At follow-up, 15 patients
(39%) had an improved VOR gain and 30 (79%) had an improved DGI score, which was
correlated (r = 0.49; 95% CI, 0.20-0.69). In those 15 patients with improved VOR
gain, 14 (93%) had improvement of DGI score. In the 23 patients without
improvement of VOR gain, 16 (70%) still showed improvement in their DGI score.
When using VOR gain to estimate improvement of DGI, the minimal clinically
important difference of VOR gain was -0.06. Conclusions and Relevance: The change
of VOR gain in the vHIT was moderately associated with the change of DGI score.
Improved VOR gain was associated with a high probability of improved dynamic
balance. However, in most of the patients whose VOR gains did not improve,
balance improvement occurred putatively through sensory reweighting strategies.
PMID- 29955787
TI - Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant
7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant
Prostate Cancer.
AB - Importance: A blood test to determine whether to treat patients with metastatic
castration-resistant prostate cancer (mCRPC) with an androgen receptor signaling
(ARS) inhibitor or taxane is an unmet medical need. Objective: To determine
whether a validated assay for the nuclear-localized androgen receptor splice
variant 7 (AR-V7) protein in circulating tumor cells can determine differential
overall survival among patients with mCRPC treated with taxanes vs ARS
inhibitors. Design, Setting, and Participants: This blinded correlative study
conducted from December 31, 2012, to September 1, 2016, included 142 patients
with histologically confirmed mCRPC and who were treated at Memorial Sloan
Kettering Cancer Center, The Royal Marsden, or the London Health Sciences Centre.
Blood samples were obtained prior to administration of ARS inhibitors or taxanes
as a second-line or greater systemic therapy for progressing mCRPC. Main Outcomes
and Measures: Overall survival after treatment with an ARS inhibitor or taxane in
relation to pretherapy AR-V7 status. Results: Among the 142 patients in the study
(mean [SD] age, 69.5 [9.6] years), 70 were designated as high risk by
conventional prognostic factors. In this high-risk group, patients positive for
AR-V7 who were treated with taxanes had superior overall survival relative to
those treated with ARS inhibitors (median overall survival, 14.3 vs 7.3 months;
hazard ratio, 0.62; 95% CI, 0.28-1.39; P = .25). Patients negative for AR-V7 who
were treated with ARS inhibitors had superior overall survival relative to those
treated with taxanes (median overall survival, 19.8 vs 12.8 months; hazard ratio,
1.67; 95% CI, 1.00-2.81; P = .05). Conclusions and Relevance: This study suggests
that nuclear-localized AR-V7 protein in circulating tumor cells can identify
patients who may live longer with taxane chemotherapy vs ARS inhibitor treatment.
PMID- 29955788
TI - "I'll Have What He's Having..." and Other Restrictions in Communicative
Participation.
PMID- 29955789
TI - The impact of luteal serum progesterone levels on live birth rates-a prospective
study of 602 IVF/ICSI cycles.
AB - STUDY QUESTION: Is the chance of a live birth following IVF treatment and fresh
embryo transfer affected by early and mid-luteal serum progesterone (P4) levels?
SUMMARY ANSWER: Low as well as high serum P4 levels in the early and mid-luteal
phase reduce the chance of a live birth following IVF treatment with fresh embryo
transfer. WHAT IS KNOWN ALREADY: Data from non-human studies and studies of
frozen-thawed embryo transfer cycles indicate that low as well as high P4 levels
during the mid-luteal phase decrease the chance of pregnancy. The altered P4
pattern may disrupt the endometrial maturation leading to asynchrony between
embryonic development and endometrial receptivity, thereby, compromising
implantation and early development of pregnancy. STUDY DESIGN, SIZE, DURATION:
Prospective multicenter cohort study of 602 women undergoing IVF treatment.
Patients were recruited from four Danish public Fertility Centers from May 2014
to June 2017. The study population was unselected, thus, representing a normal
everyday patient cohort. Patients were treated in a long GnRH-agonist protocol or
a GnRH-antagonist protocol and triggered for final oocyte maturation with either
hCG or a GnRH-agonist. The same vaginal luteal support regimen was applied in all
patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum P4 levels from the
early or mid-luteal phase were correlated to positive hCG and live birth rates
(delivery > gestational week 20). Patients were divided into four P4 groups based
on raw data of P4 serum levels and reproductive outcomes during early luteal
phase (P4<60 nmol/l, P4 60-100 nmol/l, P4 101-400 nmol/l and P4>400 nmol/l) and
during mid-luteal phase (P4<150 nmol/l, P4 150-250 nmol/l, P4 251-400 nmol/l and
P4>400 nmol/l). MAIN RESULTS AND THE ROLE OF CHANCE: The optimal chance of
pregnancy was achieved with serum P4 levels of 60-100 nmol/l in the early luteal
phase whereas the optimal P4 level during the mid-luteal phase was 150-250
nmol/l. Below, but most distinctly above these levels, the chance of pregnancy
was consistently reduced. With an early luteal P4 level of 60-100 nmol/l, the
chance of a positive hCG-test was 73%, 95% CI: [59, 84] following cleavage stage
embryo transfer. In contrast, with P4 levels >400 nmol/l, the chance of a
positive hCG-test was significantly reduced to 35%, 95% CI: [17, 57], thus, an
absolute risk difference of -38%, P = 0.01. A similar negative association
between early luteal P4 and live birth rate was found, although it did not reach
statistical significance. During the mid-luteal phase, a P4 level of 150-250
nmol/l resulted in an optimal chance of live birth: 54%, 95% CI: [37, 70]
compared to 38%, 95% CI: [20, 60] with a P4 level >400 nmol/l, thus, an absolute
risk difference of -16%, P = 0.14. All estimates were adjusted for maternal age,
maternal BMI, study site, final follicle count and late follicular P4 levels.
LIMITATIONS, REASONS FOR CAUTION: This study is the first to explore the possible
upper and lower thresholds for luteal P4 following IVF treatment and fresh embryo
transfer, and the optimal P4 ranges found in this study should be corroborated in
future clinical trials. Furthermore, the P4 thresholds in this study only apply
to fresh IVF cycles, using vaginal luteal phase support, as the optimal P4 level
in cycles using intramuscular P4 may be different. WIDER IMPLICATIONS OF THE
FINDINGS: Future studies are necessary to explore whether additional exogenous
luteal P4 supplementation in the low P4 group could increase the chance of a live
birth following fresh embryo transfer, and whether patients with luteal P4 levels
>400 nmol/l would benefit from segmentation followed by subsequent transfer in
frozen/thawed cycles. TRIAL REGISTRATION NUMBER: NCT02129998
(Clinicaltrials.gov). STUDY FUNDING/COMPETING INTEREST(S): L.H.T. received an
unrestricted grant from Ferring Pharmaceuticals, Denmark, to support this study.
P.H. received unrestricted research grants from MSD, Merck, Gedeon Richter and
Ferring Pharmaceuticals outside of this work as well as honoraria for lectures
from MSD, Merck and Gedeon Richter outside of this work. U.K. received honoraria
for lectures from MSD and Ferring Pharmaceuticals outside of this work. C.A.
received unrestricted research grants from MSD, IBSA, and Ferring Pharmaceuticals
outside of this work as well as honoraria for lectures from MSD and IBSA. H.O.E.
and B.B.P. received an unrestricted research grant from Gedeon Richter outside of
this work. K.E., L.B., D.P. and B.H. have no conflict of interest. Furthermore,
grants from 'The Health Research Fund of Central Denmark Region', 'The Research
Foundation of the Hospital of Central Jutland', 'The Research Foundation of A.P.
Moller', 'The Research Foundation of Aase & Ejnar Danielsen', 'The Research
Foundation of Dagmar Marshall', 'The Research Foundation of Dir. Jacob Madsen &
Hustru Olga Madsen', 'The Research Foundation of Fam. Hede Nielsen' and 'The
Danish Medical Research Grant' supported conducting this study. The providers of
funding were neither involved in the conduction of the study nor in the writing
of the scientific report.
PMID- 29955790
TI - The Cognitive Reserve Should Be Controlled When Using Neuroimaging to Assess
Relapse in Major Depressive Disorder.
PMID- 29955791
TI - The Objective of Local Therapy in Oligometastatic Cancer Is a Moving Target
Reply.
PMID- 29955792
TI - Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive
Metastatic Breast Cancer: A Phase 1b Clinical Trial.
AB - Importance: Treatment options for patients with disease progression after
treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1) are
limited. Tucatinib is an oral, potent, human epidermal growth factor receptor 2
(HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel
treatment for ERBB2/HER2-positive breast cancer. Objective: To determine the
maximum tolerated dosage of tucatinib in combination with T-DM1 in the treatment
of patients with ERBB2/HER2-positive metastatic breast cancer with and without
brain metastases. Design, Setting, and Participants: In this phase 1b open-label,
multicenter, clinical trial, 57 participants enrolled between January 22, 2014,
and June 22, 2015, were 18 years of age or older with ERBB2/HER2-positive
metastatic breast cancer previously treated with trastuzumab and a taxane. Data
were analyzed between January and March 2018. Interventions: Tucatinib 300 mg or
350 mg administered orally twice per day for 21 days and T-DM1 3.6 mg/kg
administered intravenously once every 21 days. Main Outcomes and Measures: Safety
assessments, pharmacokinetics, and response were assessed using RECIST 1.1 every
2 cycles for 6 cycles, followed by every 3 cycles. Results: Fifty-seven T-DM1
naive patients (median [IQR] 51 [44.0-63.0] years of age) who had undergone a
median of 2 earlier HER2 therapies (range, 1-3) were treated. The tucatinib
maximum tolerated dosage was determined to be 300 mg administered twice per day
with dose-limiting toxic reactions seen at 350 mg twice per day. Pharmacokinetic
analysis showed that there was no drug-drug interaction with T-DM1. Adverse
events seen among the 50 patients treated at the maximum tolerated dosage
regardless of causality included nausea (36 patients; 72%), diarrhea (30
patients; 60%), fatigue (28 patients; 56%), epistaxis (22 patients; 44%),
headache (22 patients; 44%), vomiting (21 patients; 42%), constipation (21
patients; 42%), and decreased appetite (20 patients; 40%); the majority of
adverse events were grade 1 or 2. Tucatinib-related toxic reactions that were
grade 3 and above included thrombocytopenia (7 patients; 14%) and hepatic
transaminitis (6 patients; 12%). Conclusions and Relevance: In this study,
tucatinib in combination with T-DM1 appeared to have acceptable toxicity and to
show preliminary antitumor activity among heavily pretreated patients with
ERBB2/HER2-positive metastatic breast cancer with and without brain metastases.
Trial Registration: ClinicalTrials.gov Identifier: NCT01983501.
PMID- 29955794
TI - Database Selection and Heterogeneity-More Details, More Credibility-Reply.
PMID- 29955793
TI - Association of MGMT Promoter Methylation Status With Survival Outcomes in
Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An
Analysis From the NRG Oncology/RTOG 0424 Trial.
AB - Importance: The initial report of NRG Oncology/Radiation Therapy Oncology Group
(RTOG) 0424 demonstrated a 3-year overall survival benefit with the addition of
temozolomide to radiotherapy compared with a historical control. However, an
important end point of the trial-evaluation of the association between O6
methylgaunine-DNA-methyltransferase (MGMT) promoter methylation and survival
outcomes-was not previously reported. Objective: To examine the proportion of
patients in NRG Oncology/RTOG 0424 with MGMT promoter methylation and its
association with survival outcomes. Design, Setting, and Participants: Specimens
collected were analyzed after trial completion to determine MGMT promoter
methylation and IDH1/2 status and the association between MGMT status and
survival outcomes. A model derived from logistic regression (MGMT-STP27) was used
to calculate MGMT promoter methylation status. Univariate and multivariable
analyses were performed using the Cox proportional hazards regression model to
determine the association of MGMT status with survival outcomes. Patient
pretreatment characteristics were included as covariates in multivariable
analyses. Main Outcomes and Measures: Progression-free survival (PFS) and overall
survival (OS). Results: Of all 129 eligible patients in NRG Oncology/RTOG 0424,
75 (58.1%) had MGMT status available (median age, 48 years; age range, 20-76
years; 42 [56.0%] male): 57 (76.0%) methylated and 18 (24.0%) unmethylated. A
total of 13 unmethylated patients (72.2%) had astrocytoma as opposed to
oligoastrocytoma or oligodendroglioma, whereas 23 methylated patients (40.4%) had
astrocytoma. On univariate analyses, an unmethylated MGMT promoter was
significantly associated with worse OS (hazard ratio [HR], 3.52; 95% CI, 1.64
7.56; P < .001) and PFS (HR, 3.06; 95% CI, 1.55-6.04; P < .001). The statistical
significances were maintained in multimarker multivariable analyses, including
IDH1/2 status for both OS (HR, 2.70; 95% CI, 1.02-7.14; P = .045) and PFS (HR,
2.74; 95% CI, 1.19-6.33; P = .02). Conclusions and Relevance: In this study, MGMT
promoter methylation was an independent prognostic biomarker of high-risk, low
grade glioma treated with temozolomide and radiotherapy. This is the first study,
to our knowledge, to validate the prognostic importance of MGMT promoter
methylation in patients with grade II glioma treated with combined radiotherapy
and temozolomide and highlights its potential prognostic value beyond IDH1/2
mutation status. Trial Registration: ClinicalTrials.gov Identifier: NCT00114140.
PMID- 29955796
TI - Preferred Clinician Communication About Stopping Cancer Screening Among Older US
Adults: Results From a National Survey.
PMID- 29955795
TI - Determination of Free 25(OH)D Concentrations and Their Relationships to Total
25(OH)D in Multiple Clinical Populations.
AB - Context: The optimal measure of vitamin D status is unknown. Objective: To
directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations
and relationships to total 25(OH)D in a clinically diverse sample of humans.
Design: Cross-sectional analysis. Setting: Seven academic sites. Patients: A
total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n =
714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79).
Interventions: Merge research data on circulating free 25(OH)D (directly-measured
immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D
binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin,
creatinine, intact parathyroid hormone, and DBP haplotype. Main outcome measures:
Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc
comparisons) and relationships between free and total 25(OH)D (mixed-effects
modeling incorporating clinical condition, DBP haplotype with sex, race,
estimated glomerular filtration rate (eGFR), body mass index (BMI), and other
covariates). Results: Free 25(OH)D was 4.7 +/- 1.8 pg/mL (mean +/- SD) in healthy
persons and 4.3 +/- 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and
0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients,
respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 +/- 3.0
pg/mL; P < 0.0033) and nursing home residents (7.9 +/- 2.1 pg/mL; P < 0.0033)
than in other groups and differed between whites and blacks (P < 0.0033) and
between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships
between free and total 25(OH)D identified clinical conditions (patients with
cirrhosis > nursing home residents > patients with prediabetes > outpatients >
pregnant women) and BMI (lesser effect) as covariates affecting relationships but
not eGFR, sex, race, or DBP haplotype. Conclusions: Total 25(OH)D, health
condition, race, and DBP haplotype affected free 25(OH)D, but only health
conditions and BMI affected relationships between total and free 25(OH)D.
Clinical importance of free 25(OH)D needs to be established in studies assessing
outcomes.
PMID- 29955797
TI - Survival Rates in Patients After Treatment for Metastasis From Uveal Melanoma.
AB - Importance: Despite high rates of local tumor control in patients who are treated
for uveal melanoma, most patients will eventually die of metastasis. When
metastasis develops, the liver is involved in most cases, and hepatic metastases
are particularly refractory to treatment. Finding effective treatments has been
challenging. A comparison of survival rates in patients who were treated for
metastasis over approximately 30 years may offer insights into progress that has
been made in prolonging survival. Objective: To compare survival after treatment
for metastasis in a cohort of patients who were treated for uveal melanoma at the
Massachusetts Eye and Ear Infirmary (MEE) during an approximately 30-year period
with an earlier analysis to determine if there was meaningful improvement in
survival rates after treatment for metastasis. Design, Setting, and Participants:
This review included patients (n = 661) who received a diagnosis of metastasis
from uveal melanoma who were identified from a cohort of 3063 patients treated at
MEE between January 1982 and December 2009 and followed up through December 2011.
They were compared with findings from a previous study of patients treated
between 1975 and 1987. Main Outcomes and Measures: Survival rates in patients who
received treatment for metastasis were compared with those who did not receive
treatment. The differences in survival rates were compared with an earlier
analysis that was completed at MEE. A comparison of patients with hepatic
metastases and extrahepatic metastases was also completed. Kaplan-Meier analysis
was used to calculate survival rates and the log rank test was used to test for
statistically significant differences between the groups. Results: Of 620
patients with race information available, 615 (97.3%) were white; the mean (SD)
age of patients was 59.71 (13.23) years and 307 (47.3%) were women. The median
time from the initial treatment of the tumor to metastasis was 3.45 years
(interquartile range [IQR], 2.0-5.57). Overall, the median survival time was poor
(3.9 months [IQR, 1.6-10.1]). Patients who received treatment fared better than
those who did not receive treatment (median survival after metastasis diagnosis,
6.3 months [IQR, 2.96-14.41] vs 1.7 months [IQR, 0.66-3.5]). This finding was
similar to that of our earlier study in which median survival was 5.2 months and
2 months for treated and untreated patients, respectively. Conclusions and
Relevance: These findings suggest that advances in treatments that lead to
clinically meaningful improvements in survival times have not been realized.
Similar survival rates in patients who were treated for metastasis were observed
in this recent analysis compared with our earlier study. Adjuvant therapies that
are initiated at the time of melanoma diagnosis may be the most effective way to
prolong survival.
PMID- 29955798
TI - Strengthening the Case for the Role of Thrombophilia in Calciphylaxis.
PMID- 29955799
TI - "Is There a Doctor on the Plane?"
PMID- 29955801
TI - Characteristics and Outcomes of Surgical Patients With Solid Cancers Admitted to
the Intensive Care Unit.
AB - Importance: Within the surgical population admitted to intensive care units
(ICUs), cancer is a common condition. However, clinicians can be reluctant to
admit patients with cancer to ICUs owing to concerns about survival. Objective:
To compare the clinical characteristics and outcomes of surgical patients with
and without cancer who are admitted to ICUs. Design, Setting, and Participants:
An observational retrospective cohort study using ICU audit records linked to
hospitalization discharge summaries, cancer registrations, and death records of
all 16 general adult ICUs in the West of Scotland was conducted. All 25 017
surgical ICU admissions between January 1, 2000, and December 31, 2011, were
included, and data analysis was conducted during that time. Exposures: Patients
were dichotomized based on a diagnosis of a solid malignant tumor as determined
by its documentation in the Scottish Cancer Registry within the 2 years prior to
ICU admission. Main Outcomes and Measures: Intensive care unit patients with
cancer were compared with ICU patients without cancer in terms of patient
characteristics (age, sex, severity of illness, reason for admission, and organ
support) and survival (ICU, hospital, 6 months, and 4 years). Results: Within the
25 017 surgical ICU patients, 13 684 (54.7%) were male, the median (interquartile
range [IQR]) age was 64 (50-74), and 5462 (21.8%) had an underlying solid tumor
diagnosis. Patients with cancer were older (median [IQR] age, 68 [60-76] vs 62
[45-74] years; P < .001) with a higher proportion of elective hospitalizations
(60.5% vs 19.8%; P < .001), similar Acute Physiology and Chronic Health
Evaluation II scores (median for both, 17), but lower use of multiorgan support
(57.9% vs 66.7%; P < .001). Intensive care unit and hospital mortality were lower
for the cancer group, at 12.2% (95% CI, 11.3%-13.1%) vs 16.8% (95% CI, 16.3%
17.4%) (P < .001) and 22.9% (95% CI, 21.8%-24.1%) vs 28.1% (27.4%-28.7%) (P <
.001). Patients with cancer had an adjusted odds ratio for hospital mortality of
1.09 (95% CI, 1.00-1.19). By 6 months, mortality in the cancer group was higher
than that in the noncancer group at 31.3% compared with 28.2% (P < .001). Four
years after ICU admission, mortality for those with and without cancer was 60.9%
vs 39.7% (P < .001) respectively. Conclusions and Relevance: Cancer is a common
diagnosis among surgical ICU patients and this study suggests that initial
outcomes compare favorably with those of ICU patients with other conditions.
Consideration that a diagnosis of cancer should not preclude admission to the ICU
in patients with surgical disease is suggested.
PMID- 29955802
TI - Pitavastatin Upregulates Nitric Oxide Synthases in the Kidney of Spontaneously
Hypertensive Rats and Wistar-Kyoto Rats.
AB - BACKGROUND: Clinical trials show potent renoprotective effects of pitavastatin
(PTV), although the precise mechanism for these renoprotective effects is not
fully clarified. The aim of this study was to examine the antihypertensive and
renoprotective effects of PTV, focusing on the nitric oxide (NO) system. METHODS:
Male, 6-week-old, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats
(WKY) were randomized to receive vehicle or PTV (2 mg/kg bodyweight) for 8 weeks.
Blood pressure and urinary albumin excretion were measured every 2 weeks. After 8
weeks, plasma biochemical parameters and renal histology were examined. NO
synthase isoform (neuronal, nNOS; inducible, iNOS; and endothelial, eNOS)
expression and eNOS phosphorylation were examined by western blotting. RESULTS:
PTV attenuated hypertension and albuminuria development in SHR. PTV decreased
glomerular desmin expression and medullary interstitial fibrosis in SHR. PTV
tended to increase plasma NO in both strains but significantly increased urinary
NO excretion only in WKY. PTV significantly increased nNOS and eNOS expression,
enhanced eNOS phosphorylation at serine1177, and inhibited eNOS phosphorylation
at threonine495 in the kidney of both strains. CONCLUSIONS: PTV treatment led to
increased renal NOS expression and upregulated eNOS activity in both SHR and WKY.
The antihypertensive and renoprotective effects of PTV may be related to
upregulation of the NO system.
PMID- 29955800
TI - Enteroendocrine profile of alpha-transducin and alpha-gustducin immunoreactive
cells in the chicken (Gallus domesticus) gastrointestinal tract.
AB - The enteroendocrine profile and distribution patterns of the taste signaling
molecules, alpha-gustducin (Galphagust) and alpha-transducin (Galphatran) protein
subunits, were studied in the gastrointestinal (GI) tract of the chicken (Gallus
domesticus) using double labeling immunohistochemistry. Galphatran or Galphagust
immunoreactivity was observed in enteroendocrine cells (EEC) expressing different
peptides throughout the entire GI tract with different density. In the
proventriculus tubular gland, Galphatran or Galphagust/gastrin (GAS)
immunoreactive (-IR) cells were more abundant than Galphatran/or Galphagust
containing glucagon-like peptide-1 (GLP-1) or peptide YY (PYY), whereas only few
Galphatran or Galphagust cells co-stored ghrelin (GHR) or 5-hydroxytryptamine (5
HT). In the pyloric mucosa, many Galphatran or Galphagust-IR cells co-expressed
GAS or GHR, with less Galphatran or Galphagust cells containing GLP-1, PYY, or 5
HT. In the small intestine, a considerable subset of Galphatran or Galphagust-IR
cells co-expressed 5-HT in the villi of the duodenum and ileum, PYY in the villi
of the jejunum, CCK or GLP-1 in the villi of the ileum, and GHR in the duodenum
crypts. In the large intestine, many Galphatran or Galphagust-IR cells contained
5-HT or GLP-1 in the villi of the rectum, whereas some Galphatran/Galphagust-IR
cells co-expressed PYY- or CCK-, and few Galphatran/Galphagust-IR cells were
positive for GHR-IR. In the cecum, several Galphatran or Galphagust-IR cells were
IR for 5-HT. Finally, many Galphatran/Galphagust cells containing 5-HT were
observed in the villi and crypts of the cloaca, whereas there were few Galphatran
or Galphagust/CCK-IR cells. The demonstration that Galpha-subunits are expressed
in the chicken GI enteroendocrine system supports the involvement of taste
signaling machinery in the chicken chemosensing processes.
PMID- 29955803
TI - Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant
Major Depression in US Veterans: A Randomized Clinical Trial.
AB - Importance: Treatment-resistant major depression (TRMD) in veterans is a major
clinical challenge given the high risk for suicidality in these patients.
Repetitive transcranial magnetic stimulation (rTMS) offers the potential for a
novel treatment modality for these veterans. Objective: To determine the efficacy
of rTMS in the treatment of TRMD in veterans. Design, Setting, and Participants:
A double-blind, sham-controlled randomized clinical trial was conducted from
September 1, 2012, to December 31, 2016, in 9 Veterans Affairs medical centers. A
total of 164 veterans with TRD participated. Interventions: Participants were
randomized to either left prefrontal rTMS treatment (10 Hz, 120% motor threshold,
4000 pulses/session) or to sham (control) rTMS treatment for up to 30 treatment
sessions. Main Outcomes and Measures: The primary dependent measure of the
intention-to-treat analysis was remission rate (Hamilton Rating Scale for
Depression score <=10, indicating that depression is in remission and not a
clinically significant burden), and secondary analyses were conducted on other
indices of posttraumatic stress disorder, depression, hopelessness, suicidality,
and quality of life. Results: The 164 participants had a mean (SD) age of 55.2
(12.4) years, 132 (80.5%) were men, and 126 (76.8%) were of white race. Of these,
81 were randomized to receive active rTMS and 83 to receive sham. For the primary
analysis of remission, there was no significant effect of treatment (odds ratio,
1.16; 95% CI, 0.59-2.26; P = .67). At the end of the acute treatment phase, 33 of
81 (40.7%) of those in the active treatment group achieved remission of
depressive symptoms compared with 31 of 83 (37.4%) of those in the sham treatment
group. Overall, 64 of 164 (39.0%) of the participants achieved remission.
Conclusions and Relevance: A total of 39.0% of the veterans who participated in
this trial experienced clinically significant improvement resulting in remission
of depressive symptoms; however, there was no evidence of difference in remission
rates between the active and sham treatments. These findings may reflect the
importance of close clinical surveillance, rigorous monitoring of concomitant
medication, and regular interaction with clinic staff in bringing about
significant improvement in this treatment-resistant population. Trial
Registration: ClinicalTrials.gov Identifier: NCT01191333.
PMID- 29955804
TI - SLIDE - a web-based tool for interactive visualization of large-scale -omics
data.
AB - Summary: Data visualization is often regarded as a post hoc step for verifying
statistically significant results in the analysis of high-throughput data sets.
This common practice leaves a large amount of raw data behind, from which more
information can be extracted. However, existing solutions do not provide
capabilities to explore large-scale raw datasets using biologically sensible
queries, nor do they allow user interaction based real-time customization of
graphics. To address these drawbacks, we have designed an open-source, web-based
tool called Systems-Level Interactive Data Exploration, or SLIDE to visualize
large-scale -omics data interactively. SLIDE's interface makes it easier for
scientists to explore quantitative expression data in multiple resolutions in a
single screen. Availability: SLIDE is publicly available under BSD license both
as an online version as well as a stand-alone version at
https://github.com/soumitag/SLIDE. Supplementary information: Supplementary
Information are available at Bioinformatics online.
PMID- 29955805
TI - Longitudinal Associations Between Visual Impairment and Cognitive Functioning:
The Salisbury Eye Evaluation Study.
AB - Importance: Worsening vision and declining cognitive functioning are common
conditions among elderly individuals. Understanding the association between them
could be beneficial in mitigating age-related cognitive changes. Objective: To
evaluate the longitudinal associations between visual impairment and cognitive
function over time in a population-based study of older US adults. Design,
Setting, and Participants: Prospective longitudinal population-based study of
older adults in the greater Salisbury area in Maryland. Overall, 2520 community
residing adults aged 65 to 84 years were assessed at baseline between September
1993 and August 1995 (round 1) and 2 (round 2), 6 (round 3), and 8 (round 4)
years later. Main Outcomes and Measures: Visual acuity (VA) was measured using
Early Treatment Diabetic Retinopathy Study charts, and cognitive status was
assessed using the Mini-Mental State Examination (MMSE). Results: Of 2520
individuals, the mean (SD) age was 73.5 (5.1) years, 1458 (58%) were women, and
666 (26%) were black. There were 2240 (89%), 1504 (61%), and 1250 (50%)
participants in the second, third, and fourth round of study, respectively, with
more than half of the loss being due to death. Both VA and MMSE score worsened
over time. The mean biannual decline of VA was 0.022 logMAR (approximately 1 line
during 8 years; 95% CI, 0.018-0.026), and the mean biannual worsening of MMSE
score was -0.59 (95% CI, -0.64 to -0.54; both P < .001). Worse baseline VA was
associated with worse baseline MMSE score (r = -0.226; 95% CI, -0.291 to -0.16; P
< .001). The rate of worsening VA was associated with the rate of declining MMSE
score (r = -0.139; 95% CI, -0.261 to -0.017; P = .03). Cross-lagged models
indicated VA in the previous round was associated with MMSE score in the
subsequent round (beta = -0.995, P < .001), and MMSE score in the previous round
was associated with VA in the following round (beta = -0.003, P < .001). However,
the standardized effect size of VA on MMSE score (beta = -0.074; SE, 0.015; P <
.001) is larger relative to the reverse effect (beta = -0.038; SE, 0.013; P <
.001), demonstrating VA is likely the driving force in these dynamic
associations. Conclusions and Relevance: In a population-based sample of older US
adults, visual impairment measured at distance is associated with declining
cognitive function both cross-sectionally and longitudinally over time with
worsening vision having a stronger association with declining cognition than the
reverse. Worsening vision in older adults may be adversely associated with future
cognitive functioning. Maintaining good vision may be an important interventional
strategy for mitigating age-related cognitive declines.
PMID- 29955806
TI - The Limits and Hazards of Clinical Equipoise on Cardiology Study Design and
Conduct.
PMID- 29955807
TI - What's the Best Way to Treat Normal-Weight People With Metabolic Abnormalities?
PMID- 29955808
TI - Perceived Facial Distortions in Selfies Are Explained by Viewing Habits.
PMID- 29955809
TI - Dyspnea and Edema in a Woman With Antiphospholipid Syndrome.
PMID- 29955811
TI - Assessing the Competence of Aging Physicians Who Are Young at Heart.
PMID- 29955810
TI - Can E-Cigarettes and Pharmaceutical Aids Increase Smoking Cessation and Reduce
Cigarette Consumption? Findings From a Nationally Representative Cohort of
American Smokers.
AB - Many smokers believe that electronic nicotine delivery systems (ENDS) and
pharmaceutical cessation aids can help them quit smoking or reduce cigarette
consumption, but the evidence for e-cigarettes to aid quitting is limited.
Examining 3,093 quit attempters in the nationally representative US Population
Assessment of Tobacco and Health (PATH) Study, using data from 2013-2015, we
evaluated the influence of ENDS and pharmaceutical cessation aids on persistent
abstinence (>=30 days) from cigarettes and reduced cigarette consumption, using
propensity score matching to balance comparison groups on potential confounders
and multiple imputation to handle missing data. At PATH Wave 2, 25.2% of quit
attempters reported using ENDS to quit during the previous year, making it the
most popular cessation aid in 2014-2015. More quit attempters were persistently
cigarette abstinent than were persistently tobacco abstinent (15.5% (standard
error, 0.8) vs. 9.6% (standard error, 0.6)). Using ENDS to quit cigarettes
increased the probability of persistent cigarette abstinence at Wave 2 (risk
difference (RD) = 6%, 95% confidence interval (CI): 2, 10), but using approved
pharmaceutical aids did not (for varenicline, RD = 2%, 95% CI: -6, 13; for
bupropion, RD = 4%, 95% CI: -6, 17; for nicotine replacement therapy, RD = -3%,
95% CI: -8, 2). Among quit attempters who relapsed, ENDS did not reduce the
average daily cigarette consumption (cigarettes per day, -0.18, 95% CI: -1.87,
1.51).
PMID- 29955813
TI - Correction of Units of Measure in a Table and the Text.
PMID- 29955812
TI - What Can We Learn From Voluntary Bundled Payment Programs?
PMID- 29955814
TI - The Search for Treatments for Veterans With Major Depression: Of Paramount
Importance, yet Still Elusive.
PMID- 29955815
TI - Ants on Clerodendrum infortunatum: Disentangling Effects of Larceny and
Herbivory.
AB - Nectar larcenists extract nectar from flowers without pollinating them. A
reasonable expectation is that any form of nectar larceny should have a
detrimental effect on the plant's reproductive success. However, studies reveal
an entire range of effects, from highly negative to highly positive. This
variation in effect may be partly explained by additional, unmeasured, effects of
nectar larcenists on plants. In a study system where two ant species Tapinoma
melanocephalum (Fabr.) (Hymenoptera: Formicidae) and Trichomyrmex destructor
(Jerd.) (Hymenoptera: Formicidae) act as nectar larcenists, we examined the
effect of larceny on the female reproductive success of Clerodendrum infortunatum
Gaertn. (Lamiales: Lamiaceae) in rain forest fragments of the Western Ghats,
India. This was done through a combination of field observations and a series of
field experiments looking at the effects of excluding ants from inflorescences.
We found that T. destructor reduces fruit set considerably. Rather than this
being a consequence of nectar larceny, however, our experiments show that the
negative effect arises instead from the herbivorous behavior of the ant. At a
population level, both ant species prefer edges over interiors of forest patches,
spatially concentrating the interaction zone to forest edges. Simultaneously
considering multiple ecological interactions and disentangling their relative
contributions might explain the large variation across species in the observed
effect of larceny. The overall population effect of nectar larceny and herbivory
is likely to depend on the spatial structuring of plants and ants.
PMID- 29955816
TI - Recommended Protocols for Instrumental Assessment of Voice: American Speech
Language-Hearing Association Expert Panel to Develop a Protocol for Instrumental
Assessment of Vocal Function.
AB - Purpose: The aim of this study was to recommend protocols for instrumental
assessment of voice production in the areas of laryngeal endoscopic imaging,
acoustic analyses, and aerodynamic procedures, which will (a) improve the
evidence for voice assessment measures, (b) enable valid comparisons of
assessment results within and across clients and facilities, and (c) facilitate
the evaluation of treatment efficacy. Method: Existing evidence was combined with
expert consensus in areas with a lack of evidence. In addition, a survey of
clinicians and a peer review of an initial version of the protocol via VoiceServe
and the American Speech-Language-Hearing Association's Special Interest Group 3
(Voice and Voice Disorders) Community were used to create the recommendations for
the final protocols. Results: The protocols include recommendations regarding
technical specifications for data acquisition, voice and speech tasks, analysis
methods, and reporting of results for instrumental evaluation of voice production
in the areas of laryngeal endoscopic imaging, acoustics, and aerodynamics.
Conclusion: The recommended protocols for instrumental assessment of voice using
laryngeal endoscopic imaging, acoustic, and aerodynamic methods will enable
clinicians and researchers to collect a uniform set of valid and reliable
measures that can be compared across assessments, clients, and facilities.
PMID- 29955817
TI - Interleukin-1 inhibition and ischaemic stroke: has the time for a major outcomes
trial arrived?
PMID- 29955818
TI - LncmiRSRN: identification and analysis of long non-coding RNA related miRNA
sponge regulatory network in human cancer.
AB - Motivation: MicroRNAs (miRNAs) are small non-coding RNAs with the length of ~22
nucleotides. miRNAs are involved in many biological processes including cancers.
Recent studies show that long non-coding RNAs (lncRNAs) are emerging as miRNA
sponges, playing important roles in cancer physiology and development. Despite
accumulating appreciation of the importance of lncRNAs, the study of their
complex functions is still in its preliminary stage. Based on the hypothesis of
competing endogenous RNAs (ceRNAs), several computational methods have been
proposed for investigating the competitive relationships between lncRNAs and
miRNA target messenger RNAs (mRNAs). However, when the mRNAs are released from
the control of miRNAs, it remains largely unknown as to how the sponge lncRNAs
influence the expression levels of the endogenous miRNA targets. Results: We
propose a novel method to construct lncRNA related miRNA sponge regulatory
networks (LncmiRSRNs) by integrating matched lncRNA and mRNA expression profiles
with clinical information and putative miRNA-target interactions. Using the
method, we have constructed the LncmiRSRNs for 4 human cancers (glioblastoma
multiforme, lung cancer, ovarian cancer and prostate cancer). Based on the
networks, we discover that after being released from miRNA control, the target
mRNAs are normally up-regulated by the sponge lncRNAs, and only a fraction of
sponge lncRNA-mRNA regulatory relationships and hub lncRNAs are shared by the 4
cancers. Moreover, most sponge lncRNA-mRNA regulatory relationships show a
rewired mode between different cancers, and a minority of sponge lncRNA-mRNA
regulatory relationships conserved (appearing) in different cancers may act as a
common pivot across cancers. Besides, differential and conserved hub lncRNAs may
act as potential cancer drivers to influence the cancerous state in cancers.
Functional enrichment and survival analysis indicate that the identified
differential and conserved LncmiRSRN network modules work as functional units in
biological processes, and can distinguish metastasis risks of cancers. Our
analysis demonstrates the potential of integrating expression profiles, clinical
information and miRNA-target interactions for investigating lncRNA regulatory
mechanism. Availability: LncmiRSRN is freely available
(https://github.com/zhangjunpeng411/LncmiRSRN). Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29955819
TI - Potential Policy Approaches to Address Diet-Related Diseases.
PMID- 29955820
TI - Caregiver oral rehydration solution fluid monitoring charts versus standard care
for the management of some dehydration among Kenyan children: a randomized
controlled trial.
AB - Background: Diarrhoea is a major cause of child mortality. Although oral
rehydration solution (ORS) is an efficacious intervention for correcting
dehydration, inadequate monitoring may limit its effectiveness in routine
settings. We evaluated the effect of using a caregiver-administered chart to
monitor oral fluid therapy on hydration status among children with some
dehydration. Methods: An open-label randomized controlled trial was conducted
among children 2-59 months of age. ORS fluid monitoring charts were given to
caregivers in the intervention arm to record the hourly intake of ORS. ORS was
administered without charting in the control arm. The primary outcome was
dehydration defined by the presence of clinical signs of some dehydration, severe
dehydration or shock assessed 4 h after initiation of treatment. We also assessed
the acceptability of the charts among caregivers. Results: We evaluated 252
patients for the primary endpoint. Among those who received the intervention,
7/122 (5.7%) were still dehydrated following 4 h of ORS administration vs 20/130
(15.4%) in the control group (risk ratio 0.37 [95% confidence interval 0.16
0.85]). Caregivers in the intervention arm reported positive experiences using
the fluid charts. Conclusions: The use of fluid monitoring charts reduced the
frequency of dehydration and was well accepted by caregivers, representing a
promising innovation for the management of diarrhoea and dehydration in resource
limited settings.
PMID- 29955821
TI - MetaboAnalystR: an R package for flexible and reproducible analysis of
metabolomics data.
AB - Summary: The MetaboAnalyst web application has been widely used for metabolomics
data analysis and interpretation. Despite its user-friendliness, the web
interface has presented its inherent limitations (especially for advanced users)
with regard to flexibility in creating customized workflow, support for
reproducible analysis, and capacity in dealing with large data. To address these
limitations, we have developed a companion R package (MetaboAnalystR) based on
the R code base of the web server. The package has been thoroughly tested to
ensure that the same R commands will produce identical results from both
interfaces. MetaboAnalystR complements the MetaboAnalyst web server to facilitate
transparent, flexible and reproducible analysis of metabolomics data.
Availability: MetaboAnalystR is freely available from https://github.com/xia
lab/MetaboAnalystR. Supplementary information: Supplementary data are available
at Bioinformatics online.
PMID- 29955822
TI - Assessment of a Density-Based Action Threshold for Suppression of Sugarcane
Aphids, (Hemiptera: Aphididae), in the Southern High Plains.
AB - In the High Plains, sugarcane aphid, Melanaphis sacchari Zehntner (Hemiptera:
Aphididae), colonize grain sorghum, Sorghum bicolor (L) Moench (Cyperales:
Poaceae), when it is in reproductive stages and aphid populations increase
rapidly. Sugarcane aphid management recommendations based on aphid densities have
been implemented in southern United States, but have not been assessed in the
High Plains. Therefore, the goal of this work was to validate whether these
guidelines can provide effective suppression of the aphids and improve yield. In
a 2-y field experiment, sorghum susceptible (DKS44-20) and resistant (DKS37-07)
to sugarcane aphids, with and without insecticide (clothianidin) seed treatments,
was exposed to natural aphid infestations and treated with a foliar insecticide
(flupyradifurone) once sugarcane aphid densities exceeded 50 per leaf. Further,
to assess the effects of these tactics on sorghum yield, data were collected from
plots that were not treated at the threshold. In both years, foliar insecticide
applied at the density-based threshold decreased aphid numbers across sorghum
hybrids with and without seed treatments and aphid densities remained below
threshold for the remainder of the season. Yield of sorghum depended on sugarcane
aphid pressure-when their densities were high (2016), the resistant hybrid with
and without the foliar spray outperformed the unsprayed susceptible hybrid, while
the susceptible hybrid had higher yields than resistant hybrid when sugarcane
aphid pressure was low (2017). Outcomes of this work support the notion that a
well-timed foliar application can alleviated losses in yield in sorghum in the
Texas Panhandle and potentially other regions of the High Plains.
PMID- 29955823
TI - Age and Treatment of Nonmelanoma Skin Cancer-Reply.
PMID- 29955825
TI - Corrigendum.
PMID- 29955824
TI - Evaluation of Linguistic Markers of Word-Finding Difficulty and Cognition in
Parkinson's Disease.
AB - Purpose: Early cognitive symptoms such as word-finding difficulty (WFD) in daily
conversation are common in Parkinson's disease (PD), but studies have been
limited by a lack of feasible, quantitative measures. Linguistic analysis,
focused on pauses in speech, may yield markers of impairment of cognition and
communication in PD. The objective of this study was to evaluate the relationship
of linguistic markers in semistructured speech to WFD symptoms and cognitive
function in PD. Method: Speech recordings of description of the Cookie Theft
picture in 53 patients with PD without dementia and 23 elderly controls were
analyzed with Praat software. Montreal Cognitive Assessment (MoCA; Nasreddine et
al., 2005), category naming fluency, and confrontation naming tests were
administered. Questionnaires rating WFD symptoms and cognitive instrumental
activities of daily living were completed. We determined the relationships
between (a) pause length and location, (b) MoCA score, and (c) WFD symptoms,
using Pearson's correlations and multivariate regression models. Results:
Compared with controls, patients with PD had more pauses within utterances as
well as fewer words per minute and a lower percentage of well-formed sentences.
Pauses within utterances differed significantly between PD-mild cognitive
impairment and normal cognition (p < .001). Words per minute and percentage of
well-formed sentences were predictive of MoCA in multivariate regression models.
Pauses before verbs were associated with patient-reported severity of WFD
symptoms (p = .006). Conclusions: Linguistic markers including pauses within
utterances distinguish patients with PD with mild cognitive symptoms from elderly
controls. These markers are associated with global cognitive function before the
onset of dementia. Pauses before verbs and grammatical markers may index early
cognitive symptoms such as WFD that may interfere with functional communication.
Supplemental Material: https://doi.org/10.23641/asha.6615401.
PMID- 29955826
TI - Associations of Combined Genetic and Lifestyle Risks With Incident Cardiovascular
Disease and Diabetes in the UK Biobank Study.
AB - Importance: Genetic and lifestyle factors both contribute to the risk of
developing cardiovascular disease, but whether poor health behaviors are
associated with similar increases in risk among individuals with low,
intermediate, or high genetic risk is unknown. Objective: To investigate the
association of combined health behaviors and factors within genetic risk groups
with coronary artery disease, atrial fibrillation, stroke, hypertension, and type
2 diabetes as well as to investigate the interactions between genetic risk and
lifestyle. Design, Setting, and Participants: The UK Biobank cohort study
includes more than 500 000 participants aged 40 to 70 years who were recruited
from 22 assessment centers across the United Kingdom from 2006 to 2010. A total
of 339 003 unrelated individuals of white British descent with available genotype
and matching genetic data and reported sex were included in this study from the
UK Biobank population-based sample. Individuals were included in the analyses of
1 or more new-onset diseases. Data were analyzed from April 2006 to March 2015.
Main Outcomes and Measures: Risks of new-onset cardiovascular disease and
diabetes associated with genetic risk and combined health behaviors and factors.
Genetic risk was categorized as low (quintile 1), intermediate (quintiles 2-4),
or high (quintile 5). Within each genetic risk group, the risks of incident
events associated with ideal, intermediate, or poor combined health behaviors and
factors were investigated and compared with low genetic risk and ideal lifestyle.
Results: Of 339 003 individuals, 181 702 (53.6%) were female, and the mean (SD)
age was 56.86 (7.99) years. During follow-up, 9771 of 325 133 participants (3.0%)
developed coronary artery disease, 7095 of 333 637 (2.1%) developed atrial
fibrillation, 3145 of 332 971 (0.9%) developed stroke, 11 358 of 234 651 (4.8%)
developed hypertension, and 4379 of 322 014 (1.4%) developed diabetes. Genetic
risk and lifestyle were independent predictors of incident events, and there were
no interactions for any outcome. Compared with ideal lifestyle in the low genetic
risk group, poor lifestyle was associated with a hazard ratio of up to 4.54 (95%
CI, 3.72-5.54) for coronary artery disease, 5.41 (95% CI, 4.29-6.81) for atrial
fibrillation, 4.68 (95% CI, 3.85-5.69) for hypertension, 2.26 (95% CI, 1.63-3.14)
for stroke, and 15.46 (95% CI, 10.82-22.08) for diabetes in the high genetic risk
group. Conclusions and Relevance: In this large contemporary population, genetic
composition and combined health behaviors and factors had a log-additive effect
on the risk of developing cardiovascular disease. The relative effects of poor
lifestyle were comparable between genetic risk groups. Behavioral lifestyle
changes should be encouraged for all through comprehensive, multifactorial
approaches, although high-risk individuals may be selected based on the genetic
risk.
PMID- 29955827
TI - A Bayesian Approach to Understanding Sex Differences in Tuberculosis Disease
Burden.
AB - Globally, men have a higher epidemiologic burden of tuberculosis (incidence,
prevalence, mortality) than women do, possibly due to differences in disease
incidence, treatment initiation, self-cure, and/or untreated-tuberculosis
mortality rates. Using a simple, sex-stratified compartmental model, we employed
a Bayesian approach to explore which factors most likely explain men's higher
burden. We applied the model to smear-positive pulmonary tuberculosis in Vietnam
(2006-2007) and Malawi (2013-2014). Posterior estimates were consistent with sex
specific prevalence and notifications in both countries. Results supported higher
incidence in men and showed that both sexes faced longer durations of untreated
disease than estimated by self-reports. Prior untreated disease durations were
revised upward 8- to 24-fold, to 2.2 (95% credible interval: 1.7, 2.9) years for
men in Vietnam and 2.8 (1.8, 4.1) years for men in Malawi, approximately a year
longer than for women in each country. Results imply that substantial sex
differences in tuberculosis burden are almost solely attributable to men's
disadvantages in disease incidence and untreated disease duration. The latter,
for which self-reports provide a poor proxy, implies inadequate coverage of case
finding strategies. These results highlight an urgent need for better
understanding of gender-related barriers faced by men and support the systematic
targeting of men for screening.
PMID- 29955828
TI - Predictors of Varenicline Adherence among Cancer Patients Treated for Tobacco
Dependence and its Association with Smoking Cessation.
AB - Introduction: The degree to which smokers adhere to pharmacotherapy predicts
treatment success. The development of interventions to increase adherence
requires identification of predictors of treatment adherence, particularly among
specific clinical populations. Methods: Using data from a 12-week open-label
phase of a clinical trial of varenicline for tobacco dependence among cancer
patients (N=207), we examined: 1) the relationship between self-reported
varenicline adherence and verified smoking cessation; and 2) demographic and
disease-related variables, and early changes in cognition, affect, withdrawal,
the reinforcing effects of smoking, and medication side effects, as correlates of
varenicline adherence. Results: At the end of 12 weeks, 35% of the sample had
quit smoking and 52% reported taking >80% of varenicline. Varenicline adherence
was associated with cessation (p <.001): 58% of participants who were adherent
had quit smoking, vs. 11% of those who were not. Participants who experienced
early reductions in depressed mood and satisfaction from smoking, and experienced
an increase in the toxic effects of smoking, showed greater varenicline adherence
(p's <.05); the relationship between greater adherence and improved cognition,
reduced craving, and reduced sleep problems and vomiting approached significance
(p's <.10). Conclusions: Among cancer patients treated for tobacco dependence
with varenicline, adherence is associated with smoking cessation. Initial changes
in depressed mood and the reinforcing effects of smoking are predictive of
adherence. Implications: The benefits of varenicline for treating tobacco
dependence among cancer patients may depend upon boosting adherence by addressing
early signs of depression and reducing the reinforcing dimensions of cigarettes.
PMID- 29955829
TI - "Do I Sound Straight?": Acoustic Correlates of Actual and Perceived Sexual
Orientation and Masculinity/Femininity in Men's Speech.
AB - Purpose: This study aims to give an integrative answer on which speech
stereotypes exist toward German gay and straight men, whether and how acoustic
correlates of actual and perceived sexual orientation are connected, and how this
relates to masculinity/femininity. Hence, it tests speech stereotype accuracy in
the context of sexual orientation. Method: Twenty-five gay and 26 straight German
speakers provided data for a fine-grained psychological self-assessment (e.g.,
masculinity/femininity) and explicit speech stereotypes. They were recorded for
an extensive set of read and spontaneous speech samples using microphones and
nasometry. Recordings were analyzed for a variety of acoustic parameters (e.g.,
fundamental frequency and nasalance). Seventy-four listeners categorized speakers
as gay or straight on the basis of the same sentence. Results: Most relevant
explicitly expressed speech stereotypes encompass voice pitch, nasality,
chromaticity, and smoothness. Demonstrating implicit stereotypes, speakers were
perceived as sounding straighter, the lower their median f0, center of gravity in
/s/, and mean F2. However, based on actual sexual orientation, straight men only
showed lower mean F1 than gay men. Additionally, we found evidence that actual
masculinity/femininity and the degree of sexual orientation were reflected in gay
and straight men's speech. Conclusion: Implicit and explicit speech stereotypes
about gay and straight men do not contain a kernel of truth, and differences
within groups are more important than differences between them. Supplemental
Material: https://doi.org/10.23641/asha.6484001.
PMID- 29955830
TI - Trophoblast plugs: impact on utero-placental haemodynamics and spiral artery
remodelling.
AB - STUDY QUESTION: How does trophoblast plugging impact utero-placental
haemodynamics? SUMMARY ANSWER: Physiological trophoblast plug structures are
dense enough to restrict flow of oxygenated blood to the intervillous space (IVS)
in the first trimester, and result in a shear stress environment upstream of the
plugs that promotes spiral artery remodelling. WHAT IS KNOWN ALREADY: Trophoblast
plugging of the uterine spiral arteries is thought to be the dominant factor
restricting the flow of oxygenated maternal blood to the placenta in the first
trimester of pregnancy. However, the extent of plugging, the timing of plug break
up, and the impact of plug structure on pregnancy outcomes is debated. STUDY
DESIGN, SIZE, DURATION: A computational model of the uterine radial and spiral
arteries, incorporating arteriovenous anastomoses was developed. The model was
parameterized with our own histological data and previous literature descriptions
of the dimensions of the spiral arteries, and the structural properties
(porosity) of trophoblast plugs. PARTICIPANTS/MATERIALS, SETTING, METHODS:
Structural data were acquired from the literature, and supplemented by images of
the spiral arteries acquired by standard thin-section 2D immunohistochemistry,
and whole mount immunohistochemistry imaged in 3D by micro-CT. Computational
models were solved using Matlab software, via custom written scripts. MAIN
RESULTS AND THE ROLE OF CHANCE: We confirm that physiological lengths (>0.1 mm)
and porosities (0.2-0.6) of trophoblast plugs are sufficient to restrict the flow
of oxygenated maternal blood flow to the placental surface. Trophoblast plugs
also have important haemodynamic consequences upstream in the spiral arteries by
generating shear stress conditions of <2 dyne/cm2 that promote trophoblast
induced spiral artery remodelling. Structural changes in plugs as they dislodge
are likely to result in rapid increases in blood flow to the IVS, and it is
likely at this stage of gestation that the major source of resistance in the
utero-placental circulation transitions from the spiral arteries to the radial
arteries, which then act as a the 'rate-limiting' step to IVS flow. LIMITATIONS,
REASONS FOR CAUTION: Structural descriptions of the spiral arteries, radial
arteries and trophoblast plugs largely rely on 2D histological sections, or
historical measurements. Increased focus on quantitatively assessing the 3D
structure of the uterine arteries using more modern imaging technologies in the
future will strengthen model predictions. WIDER IMPLICATIONS OF THE FINDINGS: Our
work suggests that trophoblast plugs play a previously under-appreciated role in
regulating spiral artery remodelling in the first trimester of human pregnancy.
This creates the possibility that inadequate trophoblast plugging in the first
trimester may contribute to the inadequate artery remodelling observed in
pregnancy pathologies such as pre-eclampsia. The incorporation of arteriovenous
anastomoses in our model highlights the important influence that shunted blood
can play in utero-placental haemodynamics, and together with the emerging role of
radial arteries in regulating blood flow to the placenta, the influence of
arteriovenous anastomoses on radial artery haemodynamics in normal and
pathological pregnancies warrants further investigation. STUDY FUNDING/COMPETING
INTEREST(S): This research was supported by a Royal Society of New Zealand
Marsden Fund award (13-UOA-032). A.R.C. is supported by a Royal Society of New
Zealand Rutherford Discovery Fellowship (14-UOA-019). R.S. was supported by a
Gravida (National Centre for Growth and Development) postgraduate scholarship.
The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
PMID- 29955831
TI - Lower serum beta-2 microglobulin levels are associated with worse survival in
incident peritoneal dialysis patients.
AB - Background: There is a general consensus that elevated serum beta-2 microglobulin
(B2M) levels measured at a single time-point are significantly associated with
mortality in patients on maintenance dialysis. To date, the majority of prior
studies that have examined B2M-associated mortality have been conducted in
prevalent hemodialysis patients with little residual renal function (RRF).
However, studies in incident peritoneal dialysis (PD) patients are lacking.
Moreover, changes in serum B2M levels over time have not been considered in this
population. Methods: We examined the association of time-updated and baseline
serum B2M levels with mortality in a 10-year cohort of 725 incident PD patients
who were maintained on dialysis between January 2006 and December 2011 using Cox
proportional hazards regression analyses. Patients were categorized into tertiles
according to B2M levels. Results: During a median follow-up of 38 (interquartile
range 23-64) months, 258 (35.4%) deaths occurred, including 106 (14.6%) and 86
(11.9%) deaths from cardiovascular and infectious causes, respectively. The
lowest B2M tertile was associated with a higher risk of all-cause and infectious
mortality compared with the middle tertile: the hazard ratios (95% confidence
interval) for all-cause deaths were 2.12 (1.38-3.26) and 2.20 (0.96-5.05) in time
varying analyses and 1.52 (1.07-2.17) and 2.41 (1.19-4.88) in baseline analyses.
Subgroup analyses showed that this association was particularly observed in
females, older patients, those with comorbidities such as diabetes, a lower body
mass index, lower albumin levels or those with higher RRF (all P for interactions
<0.05). Conclusions: In incident PD patients, lower B2M levels were independently
associated with overall and infectious mortality. These associations can be
potentially modified by malnutrition, inflammation and RRF.
PMID- 29955832
TI - Performance, behavior, and health of male broilers and laying hens of 2 dual
purpose chicken genotypes.
AB - Dual-purpose chicken where both sexes are reared together, before males are
separated for final fattening, while females are kept for an entire laying
period, may provide an economic alternative under certain production and
marketing conditions. Two genotypes, purebred Bresse-Gauloise (PURE, n = 300) and
crossbred Bresse-Gauloise * New Hampshire (CROSS, n = 300), were compared. One
day-old mixed-sex chicken were raised for 12 wk under floor husbandry conditions
on a broiler diet. Thereafter, males were transferred to a mobile chicken house
with free-range access. Males were slaughtered at weekly intervals from 12th to
19th wk of age. Hens were kept for 1 laying period in a mobile house. Growth
performance, feed consumption, carcass, meat quality, health and welfare traits
were measured in both sexes. In females layers' performance, egg quality and
behavior were recorded, too. At 12 wk, males of PURE reached a live weight of
2,075 g and CROSS of 1,865 g (P < 0.05), while at 16 wk both weighed more than
2,500 g (P > 0.05). Dressing percentage increased with slaughter age and was
above 68% in both genotypes when slaughtered at 18 to 19 wk of age. Proportion of
legs, breast, and wings was 34.3, 16.0, and 11.0% in PURE and 34.7, 15.5, and
12.1% in CROSS (P > 0.05). Laying performance was 54.5% in PURE and 54.2% in
CROSS (P > 0.05). Egg breaking strength decreased during the laying period, but
remained above 30 N. Feed conversion was 3.4 kg feed/kg egg. On average, 25% of
the animals stayed outdoors during daytime (P > 0.05). Keel bone deformations
were observed in 10% and breast blisters in 20% of the hens. Under the specific
conditions of marketing products with added value, performances resulted in an
overall economic benefit, which was higher for PURE than CROSS. The use of dual
purpose chicken to avoid the killing of 1-d-old chicken and mobile housing may
substantiate premium prices in such a system.
PMID- 29955833
TI - Usefulness of thoraco-abdominal computed tomography angiography in coronary
artery bypass patients.
AB - : OBJECTIVES: Computed tomography (CT) angiography has been widely used for
evaluating cardiovascular structures in cardiac surgical patients. The aims of
this study were to assess the prevalence of incidental findings (IF) from
preoperative thoraco-abdominal multidetector CT (MDCT) angiography, to evaluate
their clinical significance, and to elucidate predisposing factors for IF in
patients undergoing coronary artery bypass grafting (CABG). METHODS: Of the 456
patients who underwent isolated CABG between 2014 and 2016, 443 patients (97.1%)
underwent preoperative thoraco-abdominal MDCT angiography. The medical records of
patients were retrospectively reviewed, and all significant IFs that influenced
perioperative management and required additional intervention or follow-up were
analysed. RESULTS: Two hundred and ninety-two IFs having clinical significance
and affecting perioperative management were observed in 208 patients (47.0%); 231
atherosclerotic IFs in 176 patients and other 61 miscellaneous IFs in 61
patients. Twenty-nine patients had both atherosclerotic and miscellaneous IFs
with significance. A multivariable analysis demonstrated that advanced age,
chronic renal failure, recent acute myocardial infarction, and left ventricular
dysfunction were predisposing factors for IFs with significance. An additional
usefulness of MDCT angiography was evaluation of the internal thoracic artery and
the iliofemoral artery in patients whose internal thoracic artery was not
evaluated during coronary angiography (n = 119; 26.9%) and who received
perioperative peripheral mechanical circulatory support (n = 33; 7.4%),
respectively. CONCLUSIONS: Considering the high prevalence of IFs with
significance in approximately half of the patients and the additional usefulness
in one-third of the patients who underwent CABG, we recommend thoraco-abdominal
MDCT angiography for preoperative evaluation, especially in elderly patients and
those who have chronic renal failure or left ventricular dysfunction.
PMID- 29955834
TI - Guideline for Management of Pediatric Gastroesophageal Reflux.
PMID- 29955835
TI - Safety and Efficacy of Ferric Carboxymaltose in the Treatment of Iron Deficiency
Anaemia in Patients with Inflammatory Bowel Disease, in Routine Daily Practice.
AB - Introduction: Iron deficiency and iron deficiency anaemia are common
complications in inflammatory bowel disease [IBD] patients. Anaemia in IBD is
attributable to chronic blood loss and/or impaired iron intake and absorption.
International guidelines recommend intravenous iron supplementation in IBD
patients, since oral supplements are frequently poorly tolerated and can
exacerbate inflammation. Intravenous ferric carboxymaltose [FCM; Ferinject(r) 50
mg ferric iron[III]/mL suspension] was approved in Europe in 2007 for correction
of iron deficiency, and can be administered in single 15-min infusions of up to
1000 mg. Methods: A prospective non-interventional post-marketing study was
performed in 101 centres in Germany to assess the efficacy, tolerability, and
convenience of Ferinject(r) in clinical practice in a large cohort of IBD
patients. Primary endpoints were haemoglobin [Hb] normalisation or increase >=2
g/dL [responders], and normalisation of serum ferritin [s-ferritin] and
transferrin saturation. Adverse events [AEs], clinical signs/symptoms, and
disease activity indices were also analysed. Results: In all, 224 subjects (127
Crohn's disease [CD]; 97 ulcerative colitis [UC]) were treated. Mean total iron
dose was 1139 mg [range: 100 mg-4800 mg], with 76.7% of doses between 500 mg and
2000 mg; 63.3% of patients responded, and no adverse drug reactions or drug
attributed serious adverse events [SAEs] or deaths occurred. Mean increases of Hb
[10.0 to 12.3 g/dL], ferritin [52 MUg/L to 103 MUg/L], transferrin saturation
[TSAT, 15% to 25%], and s-iron [6.1 to 12.4 MUmol/L] were significant [p =
0.0001]. Clinical scores and quality of life improved due to the amelioration of
anaemia symptoms. Conclusions: Ferinject(r)-therapy was proven to be effective
and safe in a large cohort of patients with IBD-associated anaemia in routine
practice. Rapid, high-dose application is convenient for physicians and reduces
patients' time lost from work.
PMID- 29955836
TI - Quality of Life impact of a Recombinant Zoster Vaccine in adults >=50 Years of
Age.
AB - Background: To determine the efficacy of a recombinant zoster vaccine (RZV) in
reducing the herpes zoster (HZ) burden of illness, HZ burden of interference with
activities of daily living (ADLs) and HZ impact on quality of life (QoL).
Methods: The assessments were integrated in two Phase III trials, ZOE-50
(NCT01165177) and ZOE-70 (NCT01165229). HZ burden of illness and HZ burden of
interference with ADLs were assessed by the Zoster Brief Pain Inventory (ZBPI)
instrument; QoL by the EuroQol-5 Dimension (EQ-5D) utility index and the SF-36
health survey. We report the ZOE-50 results and a pooled analysis of subjects
>=70 years of age from the trials combined. Results: The estimated vaccine
efficacy (VE) in reducing HZ burden of illness as well as HZ burden of
interference was >90% in both the ZOE-50 and the pooled ZOE-70 analysis. In
confirmed HZ cases, RZV reduced the maximal ZBPI worst-pain score in the pooled
ZOE-70 analysis (p=0.032) and the maximal ZBPI average-pain scores in both the
ZOE-50 (p=0.049) and the pooled ZOE-70 analysis (p=0.043). In breakthrough HZ
cases, trends for diminished loss of QoL compared to placebo-recipient HZ cases
were observed, with differences up to 0.14 on the EQ-5D index at time points
during the four weeks following HZ onset. Conclusions: RZV reduced the HZ burden
of illness significantly, particularly due to its very high VE in preventing HZ.
For breakthrough HZ cases, the results suggest that RZV mitigated severity of HZ
related pain, burden of interference with ADLs and recipients' utility loss.
PMID- 29955837
TI - Are heterozygous carriers for hereditary fructose intolerance predisposed to
metabolic disturbances when exposed to fructose?
AB - Background: High fructose intake causes hepatic insulin resistance and increases
postprandial blood glucose, lactate, triglyceride, and uric acid concentrations.
Uric acid may contribute to insulin resistance and dyslipidemia in the general
population. In patients with hereditary fructose intolerance, fructose
consumption is associated with acute hypoglycemia, renal tubular acidosis, and
hyperuricemia. Objective: We investigated whether asymptomatic carriers for
hereditary fructose intolerance (HFI) would have a higher sensitivity to adverse
effects of fructose than would the general population. Design: Eight subjects
heterozygous for HFI (hHFI; 4 men, 4 women) and 8 control subjects received a low
fructose diet for 7 d and on the eighth day ingested a test meal, calculated to
provide 25% of the basal energy requirement, containing 13C-labeled fructose
(0.35 g/kg), glucose (0.35 g/kg), protein (0.21 g/kg), and lipid (0.22 g/kg).
Glucose rate of appearance (GRa, calculated with [6,6-2H2]glucose), fructose, net
carbohydrate, and lipid oxidation, and plasma triglyceride, uric acid, and
lactate concentrations were monitored over 6 h postprandially. Results:
Postprandial GRa, fructose, net carbohydrate, and lipid oxidation, and plasma
lactate and triglyceride concentrations were not significantly different between
the 2 groups. Postprandial plasma uric acid increased by 7.2% compared with
fasting values in hHFI subjects (P < 0.01), but not in control subjects (-1.1%,
ns). Conclusions: Heterozygous carriers of hereditary fructose intolerance had no
significant alteration of postprandial fructose metabolism compared with control
subjects. They did, however, show a postprandial increase in plasma uric acid
concentration that was not observed in control subjects in responses to ingestion
of a modest amount of fructose. This trial was registered at the US Clinical
Trials Registry as NCT02979106.
PMID- 29955839
TI - Management of Ventricular Arrhythmias and Sudden Cardiac Death Risk Associated
With Cardiac Channelopathies.
PMID- 29955838
TI - Higher spermidine intake is linked to lower mortality: a prospective population
based study.
AB - Background: Spermidine administration is linked to increased survival in several
animal models. Objective: The aim of this study was to test the potential
association between spermidine content in diet and mortality in humans. Design:
This prospective community-based cohort study included 829 participants aged 45
84 y, 49.9% of whom were male. Diet was assessed by repeated dietitian
administered validated food-frequency questionnaires (2540 assessments) in 1995,
2000, 2005, and 2010. During follow-up between 1995 and 2015, 341 deaths
occurred. Results: All-cause mortality (deaths per 1000 person-years) decreased
across thirds of increasing spermidine intake from 40.5 (95% CI: 36.1, 44.7) to
23.7 (95% CI: 20.0, 27.0) and 15.1 (95% CI: 12.6, 17.8), corresponding to an age
, sex- and caloric intake-adjusted 20-y cumulative mortality incidence of 0.48
(95% CI: 0.45, 0.51), 0.41 (95% CI: 0.38, 0.45), and 0.38 (95% CI: 0.34, 0.41),
respectively. The age-, sex- and caloric ratio-adjusted HR for all-cause death
per 1-SD higher spermidine intake was 0.74 (95% CI: 0.66, 0.83; P < 0.001).
Further adjustment for lifestyle factors, established predictors of mortality,
and other dietary features yielded an HR of 0.76 (95% CI: 0.67, 0.86; P < 0.001).
The association was consistent in subgroups, robust against unmeasured
confounding, and independently validated in the Salzburg Atherosclerosis
Prevention Program in Subjects at High Individual Risk (SAPHIR) Study (age-, sex
, and caloric ratio-adjusted HR per 1-SD higher spermidine intake: 0.71; 95% CI:
0.53, 0.95; P = 0.019). The difference in mortality risk between the top and
bottom third of spermidine intakes was similar to that associated with a 5.7-y
(95% CI: 3.6, 8.1 y) younger age. Conclusion: Our findings lend epidemiologic
support to the concept that nutrition rich in spermidine is linked to increased
survival in humans. This trial was registered at www.clinicaltrials.gov as
NCT03378843.
PMID- 29955840
TI - Unmasking the impact of Rictor in cancer: novel insights of mTORC2 complex.
AB - Genomic alterations affecting components of the mechanistic target of rapamycin
(mTOR) pathway are found rather frequently in cancers, suggesting that aberrant
pathway activity is implicated in oncogenesis of different tumor types. mTOR
functions as the core catalytic kinase of two distinct complexes, mTOR complex 1
(mTORC1) and 2 (mTORC2), which control numerous vital cellular processes. There
is growing evidence indicating that Rictor, an essential subunit of the mTORC2
complex, is inappropriately overexpressed across numerous cancer types and this
is associated with poor survival. To date, the candidate mechanisms responsible
for aberrant Rictor expression described in cancer are two: i) gene amplification
and ii) epigenetic regulation, mainly by microRNAs. Moreover, different mTOR
independent Rictor-containing complexes with oncogenic role have been documented,
revealing alternative routes of Rictor-driven tumorigenesis, but simultaneously,
paving the way for identifying novel biomarkers and therapeutic targets. Here, we
review the main preclinical and clinical data regarding the role of Rictor in
carcinogenesis and metastatic behavior as well as the potentiality of its
alteration as a target.
PMID- 29955841
TI - Speech and Communicative Participation in Patients With Facial Paralysis.
AB - Importance: Problems with speech in patients with facial paralysis are frequently
noted by both clinicians and the patients themselves, but limited research exists
describing how facial paralysis affects verbal communication. Objective: To
assess the influence of facial paralysis on communicative participation. Design,
Setting, and Participants: A nationwide online survey of 160 adults with
unilateral facial paralysis was conducted from March 1 to June 1, 2017. To assess
communicative participation, respondents completed the Communicative
Participation Item Bank (CPIB) Short Form questionnaire and the Facial
Clinimetric Evaluation (FaCE) Scale. Main Outcomes and Measures: The CPIB Short
Form and the correlation between the CPIB Short Form and FaCE Scale. In the CPIB,
the level of interference in communication is rated on a 4-point Likert scale
(where not at all = 3, a little = 2, quite a bit = 1, and very much = 0). Total
scores for the 10 items range from 0 (worst) to 30 (best). The FaCE Scale is a 15
item instrument that produces an overall score ranging from 0 (worst) to 100
(best), with higher scores representing better function and higher quality of
life. Results: Of the 160 respondents, 145 (90.6%) were women and 15 were men
(mean [SD] age, 45.1 [12.6] years). Most respondents reported having facial
paralysis for more than 3 years. Causes of facial paralysis included Bell palsy
(86 [53.8%]), tumor (41 [25.6%]), and other causes (33 [20.6%]), including
infection, trauma, congenital defects, and surgical complications. The mean (SD)
score on the CPIB Short Form was 0.16 (0.88) logits (range, -2.58 to 2.10
logits). The mean (SD) score of the FaCE Scale was 40.92 (16.05) (range, 0-83.3).
Significant correlations were observed between the CPIB Short Form and overall
FaCE Scale scores, as well as the Social Function, Oral Function, Facial Comfort,
and Eye Comfort subdomains of the FaCE Scale, but not with the Facial Movement
subdomain. Conclusions and Relevance: Patients with facial paralysis in this
study sample reported restrictions in communicative participation that were
comparable with restrictions experienced by patients with other known
communicative disorders, such as laryngectomy and head and neck cancer. We
believe that communicative participation represents a unique domain of
dysfunction and can help quantify the outcome of facial paralysis and provide an
additional frame of reference when assessing treatment outcomes.
PMID- 29955843
TI - Intracardiac cement embolism resulting in tricuspid regurgitation.
AB - Bone cement leakage is a common complication after percutaneous kyphoplasty. In
rare cases, leakage into the venous system occurs, which can be life-threatening,
especially when it embolizes the heart. Here, we present a case of cement
embolization of the right ventricle with tricuspid valve involvement. A 69-year
old woman with an asymptomatic severe tricuspid valve regurgitation was referred
to our department. She had a history of balloon kyphoplasty because of
osteoporotic collapsed vertebrae in 2010. Echocardiography showed a foreign body
attached to the right ventricle, prolapsing into the right atrium and causing a
severe tricuspid valve regurgitation. The foreign body was surgically removed,
and the tricuspid valve was replaced with a biological valve. The foreign body
was analysed by scanning electron microscopy and element analysis. Zirconium was
identified within the foreign body, which is an additive in bone cement used in
orthopaedic surgery. Intracardiac cement embolism following percutaneous
kyphoplasty is a rare but life-threatening complication. Here, we present a case
of tricuspid valve destruction caused by the long-term presence of an
intracardiac foreign body, specifically a cement embolus.
PMID- 29955842
TI - The transcription-coupled DNA repair-initiating protein CSB promotes XRCC1
recruitment to oxidative DNA damage.
AB - Transcription-coupled nucleotide excision repair factor Cockayne syndrome protein
B (CSB) was suggested to function in the repair of oxidative DNA damage. However
thus far, no clear role for CSB in base excision repair (BER), the dedicated
pathway to remove abundant oxidative DNA damage, could be established. Using live
cell imaging with a laser-assisted procedure to locally induce 8-oxo-7,8
dihydroguanine (8-oxoG) lesions, we previously showed that CSB is recruited to
these lesions in a transcription-dependent but NER-independent fashion. Here we
showed that recruitment of the preferred 8-oxoG-glycosylase 1 (OGG1) is
independent of CSB or active transcription. In contrast, recruitment of the BER
scaffolding protein, X-ray repair cross-complementing protein 1 (XRCC1), to 8
oxoG lesions is stimulated by CSB and transcription. Remarkably, recruitment of
XRCC1 to BER-unrelated single strand breaks (SSBs) does not require CSB or
transcription. Together, our results suggest a specific transcription-dependent
role for CSB in recruiting XRCC1 to BER-generated SSBs, whereas XRCC1 recruitment
to SSBs generated independently of BER relies predominantly on PARP activation.
Based on our results, we propose a model in which CSB plays a role in
facilitating BER progression at transcribed genes, probably to allow XRCC1
recruitment to BER-intermediates masked by RNA polymerase II complexes stalled at
these intermediates.
PMID- 29955844
TI - Neuronal Responses to a Postural Dual-Task With Differential Attentional
Prioritizations: Compensatory Resource Allocation With Healthy Aging.
AB - Objectives: Restricted central processing in older adults prevents optimization
of a dual task with a flexible prioritization strategy. This study investigated
the neural mechanisms of task-priority in young and older adults when performing
a posture-motor dual-task. Method: Sixteen healthy young and 16 older adults
performed a force-matching task on a mobile-platform under posture-focus (PF) and
supraposture-focus (SF) conditions. The platform movement, force-matching
performance, and event-related potentials in the preparatory period were
recorded. Results: For the elders, the postural stability and force-matching
accuracy using the PF strategy were inferior to those using the SF strategy;
whereas, the dual-task performances of the young adults were less affected by the
prioritization. Only the elders exhibited the P1 wave, with the PF strategy
associated with a smaller P1 and larger P1 than the SF strategy in the
sensorimotor-parietal and right frontotemporal areas, respectively. The PF
strategy also led to a larger P2 wave in the right frontotemporal area of elders,
but a greater P2 wave in the sensorimotor-parietal area of young adults.
Discussion: For both prioritization strategies, older adults entailed a longer
preparatory process than younger adults. Dual-task performance of older adults
was more vulnerable to PF strategy, underlying compensatory resource allocation
in the preparatory period for resolution of dual-task interference due to
degenerated frontal function.
PMID- 29955845
TI - Predictors of Renal Function and Calcifications in Primary Hyperparathyroidism: A
Nested Case-Control Study.
AB - Context: Some patients with primary hyperparathyroidism (PHPT) develop renal
calcifications. Investigation of urinary and nonurinary risk factors are
essential. Objective: We aimed to study the prevalence and potential biochemical
predictors of renal calcifications. Design: Nested case-control study. Setting:
University hospital. Participants: We identified 792 patients with PHPT from 2005
to 2015. We used biochemical data to validate the diagnosis of PHPT. Main Outcome
Measures: The prevalence of renal calcifications defined as nephrolithiasis or
nephrocalcinosis assessed by a routine CT scan at the time of diagnosis. Results:
A total of 792 patients with PHPT were identified among whom 617 patients (78%)
had a CT scan preformed. We found a prevalence of renal calcifications of 23%,
equally frequent between sexes. A total of 76 patients (12%) had nephrolithiasis
and 75 patients (12%) had nephrocalcinosis where 7 patients (1%) had both
nephrolithiasis and nephrocalcinosis. Compared with patients without renal
calcifications, patients with renal calcifications had significantly higher
levels of ionized calcium, parathyroid hormone, and 24-hour calcium excretion
(Pall < 0.01). Patients with nephrocalcinosis had higher plasma levels of
phosphate and a higher calcium-phosphate product compared with patients with
nephrolithiasis (Pall < 0.05). Impaired renal function (estimated glomerular
filtration rate <60 mL/min) was observed in 12% of patients. However, no
differences in renal function were observed between those with and without renal
calcifications. Conclusion: Renal calcifications are frequent in patients with
PHPT and are associated with the severity of the disease. Impaired renal function
is also common in PHPT, but renal function was not associated with renal
calcifications.
PMID- 29955847
TI - Leptin Regulation of Cancer Stem Cells in Breast and Gynecologic Cancer.
AB - It is well established that obesity increases the incidence and worsens the
prognosis of women's cancer. For breast cancer, women with obesity exhibit more
than a twofold increase in the odds of being diagnosed with cancer, with a
greater risk of advanced stage at diagnosis, and <=40% greater risk of recurrence
and death than their normal-weight counterparts. These findings are similar in
gynecologic cancers, where women who are obese with a body mass index (BMI) >40
kg/m2 have up to six times greater risk of developing endometrial cancer and a
9.2% increase in mortality with every 10% increase in BMI. Likewise, patients
with obesity exhibit a twofold higher risk of premenopausal ovarian cancer, and
patients who are obese with advanced stage ovarian cancer have shown a shorter
time to recurrence and poorer overall survival. Obesity is accompanied by changes
in expression of adipose factors that act on local tissues and systemically. Once
obesity was recognized as a factor in cancer incidence and progression, the
adipose cytokine (adipokine) leptin became the focus of intense investigation as
a putative link, with nearly 3000 publications on the topic. Leptin has been
shown to increase cell proliferation, inhibit apoptosis, promote angiogenesis,
and increase therapeutic resistance. These characteristics are associated with a
subset of cells in both liquid and solid tumors known as cancer stem cells
(CSCs), or tumor initiating cells. We will review the literature discussing
leptin's role in breast and gynecologic cancer, focusing on its role in CSCs, and
consider goals for targeting future therapy in this arena to disrupt tumor
initiation and progression in women's cancer.
PMID- 29955846
TI - The evolution of donation after circulatory death renal transplantation: a decade
of experience.
AB - Background: This study compared long-term outcomes of renal transplantation from
donors following donation after circulatory death (DCD) with those following
donation after brain death (DBD) from one of the largest centres in the UK.
Method: Recipients of renal transplants from deceased donors between 2002 and
2014 were identified from a prospectively maintained database. Outcomes were
compared between DCD (468) and DBD (905) donors and between standard criteria
donors (SCDs) and extended criteria donors (ECDs). Results: Graft survival (GS)
and patient survival (PS) from DCD and DBD donors were comparable up to 10 years
(GS: 61 versus 55%, P = 0.780; PS: 78 versus 71%, P = 0.285, respectively). Graft
function was comparable after 3 months. GS and function were worse in the ECD
groups, with no difference between EC-DBD and EC-DCD. PS in the ECD groups was
worse than the SCD groups and PS in the EC-DCD group was worse than in the EC-DBD
group. DCD donors were an independent risk factor for delayed graft function.
Post-operative complications and EC-DCD donation were independent risk factors
for reduced GS and PS. Conclusion: This study supports the use of DCD renal
grafts with comparable long-term survival and function to DBD grafts. The use of
EC-DCD grafts is justified in selected recipients and provides acceptable
function and survival advantages over dialysis.
PMID- 29955848
TI - Suitability of Pollen from Different Plant Species as Alternative Food Sources
for Neoseiulus californicus (Acari: Phytoseiidae) in Comparison with a Natural
Prey.
AB - Alternative foods such as pollen may help predators to maintain their populations
even when their prey is scarce or absent. In order to develop an appropriate
spider mite management strategy using Neoseiulus californicus McGregor and
optimize laboratory rearing, its biological parameters on four types of pollen
(cedar, pistachio, pear, and apricot) were determined and compared on Tetranychus
urticae Koch. Our results indicated that the developmental times of females and
males varied from 6.06 to 7.32, and 6.00 to 7.15 d, respectively. The highest
fecundity was obtained on pistachio pollen, followed by apricot pollen and T.
urticae. Feeding on cedar pollen caused the lowest fecundity. In contrast to T.
urticae and pistachio pollen, which resulted in the highest intrinsic and finite
rates of increase, feeding on cedar pollen produced the lowest value. Pistachio
and apricot pollen appear to have the highest nutritional value. From an
ecological perspective, in the presence of pistachio pollen, a more rapid
population increase of N. californicus could be expected, when the prey is scarce
or absent in greenhouses or fields. This may provide valuable information for the
design of a comprehensive program for conservation and/or mass production of N.
californicus to control T. urticae and other pests.
PMID- 29955849
TI - Application of net reclassification index to non-nested and point-based risk
prediction models: a review.
AB - Much of medical risk prediction involves externally derived prediction equations,
nomograms, and point-based risk scores. These settings are vulnerable to
misleading findings of incremental value based on versions of the net
reclassification index (NRI) in common use. By applying non-nested models and
point-based risk scores in the setting of stroke risk prediction in patients with
atrial fibrillation (AF), we demonstrate current recommendations for presentation
and interpretation of the NRI. We emphasize pitfalls that are likely to occur
with point-based risk scores that are easy to neglect when statistical
methodology is focused on continuous models. In order to make appropriate
decisions about risk prediction and personalized medicine, physicians,
researchers, and policy makers need to understand the strengths and limitations
of the NRI.
PMID- 29955850
TI - Incidence of Lyme Disease Diagnosis in a Maryland Medicaid Population, 2004-2011.
AB - The epidemiology of Lyme disease has been examined utilizing insurance claims
from privately insured individuals; however, it is unknown whether reported
patterns vary among the publicly insured. We examined trends in incidence rates
of first Lyme disease diagnosis among 384,652 Maryland Medicaid recipients
enrolled from July 2004 to June 2011. Age-, sex-, county-, season-, and year
specific incidence rates were calculated, and mixed-effects multiple logistic
regression models were used to study the relationship between Lyme disease
diagnosis and these variables. The incidence rate in our sample was 97.65 cases
per 100,000 person-years (95% confidence interval (CI): 91.53, 104.06), and there
was a 13% average annual increase in the odds of a Lyme disease diagnosis (odds
ratio = 1.13, 95% CI: 1.09, 1.17; P < 0.001). Incidence rates for males and
females were not significantly different, though males were significantly more
likely to be diagnosed during high-season months (relative risk (RR) = 1.24, 95%
CI: 1.06, 1.44) and less likely to be diagnosed during low-season months (RR =
0.63, 95% CI: 0.46, 0.87) than females. Additionally, adults were significantly
more likely than children to be diagnosed during low-season months (RR = 1.59,
95% CI: 1.19, 2.12). While relatively rare in this study sample, Lyme disease
diagnoses do occur in a Medicaid population in a Lyme-endemic state.
PMID- 29955851
TI - Antiviral treatment for outpatient use during an influenza pandemic: a decision
tree model of outcomes averted and cost-effectiveness.
AB - Background: Many countries have acquired antiviral stockpiles for pandemic
influenza mitigation and a significant part of the stockpile may be focussed
towards community-based treatment. Methods: We developed a spreadsheet-based,
decision tree model to assess outcomes averted and cost-effectiveness of
antiviral treatment for outpatient use from the perspective of the healthcare
payer in the UK. We defined five pandemic scenarios-one based on the 2009 A(H1N1)
pandemic and four hypothetical scenarios varying in measures of transmissibility
and severity. Results: Community-based antiviral treatment was estimated to avert
14-23% of hospitalizations in an overall population of 62.28 million. Higher
proportions of averted outcomes were seen in patients with high-risk conditions,
when compared to non-high-risk patients. We found that antiviral treatment was
cost-saving across pandemic scenarios for high-risk population groups, and cost
saving for the overall population in higher severity influenza pandemics.
Antiviral effectiveness had the greatest influence on both the number of
hospitalizations averted and on cost-effectiveness. Conclusions: This analysis
shows that across pandemic scenarios, antiviral treatment can be cost-saving for
population groups at high risk of influenza-related complications.
PMID- 29955853
TI - Erratum to Clinoptilolite in Dextran Sulphate Sodium-Induced Murine Colitis:
Efficacy and Safety of a Microparticulate Preparation.
PMID- 29955852
TI - Efficacy of Ebola Glycoprotein-Specific Equine Polyclonal Antibody Product
Against Lethal Ebola Virus Infection in Guinea Pigs.
AB - Background: Filoviruses including Ebola, Sudan, and other species are emerging
zoonotic pathogens representing a significant public health concern with high
outbreak potential, and they remain a potential bioterrorism-related threat. We
have developed a despeciated equine Ebola polyclonal antibody (E-EIG)
postexposure treatment against Ebola virus (EBOV) and evaluated its efficacy in
the guinea pig model of EBOV infection. Methods: Guinea pigs were infected with
guinea pig-adapted EBOV (Mayinga strain) and treated with various dose levels of
E-EIG (20-100 mg/kg) twice daily for 6 days starting at 24 h postinfection. The E
EIG was also assessed for neutralization activity against related filoviruses
including EBOV strains Mayinga, Kikwit, and Makona and the Bundibugyo and Tai
Forest ebolavirus species. Results: Treatment with E-EIG conferred 83% to 100%
protection in guinea pigs. The results demonstrated a comparable neutralization
activity (range, 1:512-1:896) of E-EIG against all tested strains, suggesting the
potential for cross-protection with the polyclonal antibody therapeutic.
Conclusions: This study showed that equine-derived polyclonal antibodies are
efficacious against lethal EBOV disease in a relevant animal model. Furthermore,
the studies support the utility of the equine antibody platform for the rapid
production of a therapeutic product in the event of an outbreak by a filovirus or
other zoonotic pathogen.
PMID- 29955854
TI - Iron Deficiency Anemia in Patients Undergoing Extracorporeal Photopheresis for
Cutaneous T-Cell Lymphoma.
AB - Objective: To describe the indicidence and severity of iron deficiency anemia
(IDA) in patients who have received extracorporeal photopheresis (ECP) treatment
of cutaneous T-cell lymphoma (CTCL). Methods: We performed a retrospective study
during a 9-year period of patients with CTCL who were treated with ECP. ECP was
performed with UVAR XTS and CELLEX (Therakos Inc). IDA was defined by a drop in
hemoglobin (Hb), mean cell volume (MCV), and increased red blood cell
distribution width (RDW). Results: We identified a total of 36 patients; 1
patient was excluded due to severe anemia. In 35 patients, initial hemoglobin
values ranged from 9.8 g per dL to 15.9 g per dL, and patients received 4 to 327
ECP treatments. In all, 28 patients showed decreases in Hb of 0.8 g per dL to 6 g
per dL during treatments. Conclusion: Chronic ECP led to IDA in 28 of 35 patients
with CTCL. IDA occurs due to blood loss when ECP equipment does not return full
blood volume to patients.
PMID- 29955855
TI - Commentary on: Integrated Forehead and Temporal Augmentation Using 3D Printing
Assisted Methyl Methacrylate Implants.
PMID- 29955856
TI - KATP Channel Blockade as a Novel Antiarrhythmic Strategy: Evolving From Tachy to
Brady Therapy.
PMID- 29955857
TI - Association of Cataract Surgery With Traffic Crashes.
AB - Importance: Cataracts are the most common cause of impaired vision worldwide and
may increase a driver's risk of a serious traffic crash. The potential benefits
of cataract surgery for reducing a patient's subsequent risk of traffic crash are
uncertain. Objective: To conduct a comprehensive longitudinal analysis testing
whether cataract surgery is associated with a reduction in serious traffic
crashes where the patient was the driver. Design, Setting, and Participants:
Population-based individual-patient self-matching exposure-crossover design in
Ontario, Canada, between April 1, 2006, and March 31, 2016. Consecutive patients
65 years and older undergoing cataract surgery (n = 559 546). Interventions:
First eye cataract extraction surgery (most patients received second eye soon
after). Main Outcomes and Measures: Emergency department visit for a traffic
crash as a driver. Results: Of the 559 546 patients, mean (SD) age was 76 (6)
years, 58% were women (n = 326 065), and 86% lived in a city (n = 481 847). A
total of 4680 traffic crashes (2.36 per 1000 patient-years) accrued during the
3.5-year baseline interval and 1200 traffic crashes (2.14 per 1000 patient-years)
during the 1-year subsequent interval, representing 0.22 fewer crashes per 1000
patient-years following cataract surgery (odds ratio [OR], 0.91; 95% CI, 0.84
0.97; P = .004). The relative reduction included patients with diverse
characteristics. No significant reduction was observed in other outcomes, such as
traffic crashes where the patient was a passenger (OR, 1.03; 95% CI, 0.96-1.12)
or pedestrian (OR, 1.02; 95% CI, 0.88-1.17), nor in other unrelated serious
medical emergencies. Patients with younger age (OR, 1.27; 95% CI, 1.13-1.14),
male sex (OR, 1.64; 95% CI, 1.46-1.85), a history of crash (baseline OR, 2.79;
95% CI, 1.94-4.02; induction OR, 4.26; 95% CI, 2.01-9.03), more emergency visits
(OR, 1.34; 95% CI, 1.19-1.52), and frequent outpatient physician visits (OR,
1.17; 95% CI, 1.01-1.36) had higher risk of subsequent traffic crashes
(multivariable model). Conclusions and Relevance: This study suggests that
cataract surgery is associated with a modest decrease in a patient's subsequent
risk of a serious traffic crash as a driver, which has potential implications for
mortality, morbidity, and costs to society.
PMID- 29955859
TI - A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious
Diseases: 2018 Update by the Infectious Diseases Society of America and the
American Society for Microbiology.
AB - The critical nature of the microbiology laboratory in infectious disease
diagnosis calls for a close, positive working relationship between the
physician/advanced practice provider and the microbiologists who provide enormous
value to the healthcare team. This document, developed by experts in laboratory
and adult and pediatric clinical medicine, provides information on which tests
are valuable and in which contexts, and on tests that add little or no value for
diagnostic decisions. This document presents a system-based approach rather than
specimen-based approach, and includes bloodstream and cardiovascular system
infections, central nervous system infections, ocular infections, soft tissue
infections of the head and neck, upper and lower respiratory infections,
infections of the gastrointestinal tract, intra-abdominal infections, bone and
joint infections, urinary tract infections, genital infections, and other skin
and soft tissue infections; or into etiologic agent groups, including arthropod
borne infections, viral syndromes, and blood and tissue parasite infections. Each
section contains introductory concepts, a summary of key points, and detailed
tables that list suspected agents; the most reliable tests to order; the samples
(and volumes) to collect in order of preference; specimen transport devices,
procedures, times, and temperatures; and detailed notes on specific issues
regarding the test methods, such as when tests are likely to require a
specialized laboratory or have prolonged turnaround times. In addition, the
pediatric needs of specimen management are also emphasized. There is intentional
redundancy among the tables and sections, as many agents and assay choices
overlap. The document is intended to serve as a guidance for physicians in
choosing tests that will aid them to quickly and accurately diagnose infectious
diseases in their patients.
PMID- 29955858
TI - An Autonomic Network: Synchrony Between Slow Rhythms of Pulse and Brain Resting
State Is Associated with Personality and Emotions.
AB - The sympathetic system's role in modulating vasculature and its influence on
emotions and personality led us to test the hypothesis that interactions between
brain resting-state networks (RSNs) and pulse amplitude (indexing sympathetic
activity) would be associated with emotions and personality. In 203 participants,
we characterized RSN spatiotemporal characteristics, and phase-amplitude
associations of RSN fluctuations with pulse and respiratory recordings. We found
that RSNs are spatially reproducible within participants and were temporally
associated with low frequencies (LFs < 0.1 Hz) in physiological signals. LF
fluctuations in pulse amplitude were not related to cardiac electrical activity
and preceded LF fluctuations in RSNs, while LF respiratory amplitude fluctuations
followed LF fluctuations in RSNs. LF phase dispersion (PD) (lack of synchrony)
between RSNs and pulse (PDpulse) (not respiratory) correlated with the common
variability in measures of personality and emotions, with more synchrony being
associated with more positive temperamental characteristics. Voxel-level PDpulse
mapping revealed an "autonomic brain network," including sensory cortices and
dorsal attention stream, with significant interactions with peripheral signals.
Here, we uncover associations between pulse signal amplitude (presumably of
sympathetic origin) and brain resting state, suggesting that interactions between
central and autonomic nervous systems are important for characterizing
personality and emotions.
PMID- 29955860
TI - Rice H2A.Z negatively regulates genes responsive to nutrient starvation but
promotes expression of key housekeeping genes.
AB - The H2A.Z histone variant plays a role in the modulation of environmental
responses, but the nature of the associated mechanisms remains enigmatic. We
investigated global H2A.Z deposition and transcriptomic changes in rice (Oryza
sativa) upon exposure to phosphate (Pi) deficiency and in response to RNAi
knockdown of OsARP6, which encodes a key component of the H2A.Z exchange complex.
Both Pi deficiency and OsARP6-knockdown resulted in similar, profound effects on
global H2A.Z distribution. H2A.Z in the gene body of stress-responsive genes was
negatively correlated with gene expression, and this was more apparent in
response to Pi deficiency. In contrast, the role of H2A.Z at the transcription
start site (TSS) was more context dependent, acting as a repressor of some stress
responsive genes, but an activator of some genes with housekeeping functions.
This was especially evident upon OsARP6-knockdown, which resulted in down
regulation of a number of genes linked to chloroplast function that contained
decreases in H2A.Z at the TSS. Consistently, OsARP6-RNAi plants exhibited lower
chlorophyll content relative to the wild-type. Our results demonstrate that gene
body-localized H2A.Z plays a prominent role in repressing stress-responsive genes
under non-inductive conditions, whereas H2A.Z at the TSS functions as a positive
or negative regulator of transcription.
PMID- 29955861
TI - Reasons for Proficiency Testing Failures in Routine Chemistry Analysis in China.
AB - Objective: To understand the reasons for proficiency testing (PT) failures,
toward the goal of continuous improvement of laboratory services. Methods:
Laboratories participating in PT of routine chemistry testing provided by the
National Center for Clinical Laboratories (NCCL) of China were given 3 schemes
for handling PT failures in 2016. If they had unsatisfactory PT performance, they
were notified and requested to investigate failure errors and submit data
regarding those errors. Results: Failure types were distributed as follows, per
error group: Clerical, 10.2%; Methodological, 16.2%; Equipment, 23.6%; Technical,
37.4%; PT Evaluation, 0.5%; Unexplained, 11.5%; and Other, 0.7%. Reasons unique
to the PT process accounted for 15.6% of all reasons. Corrective actions mainly
included correcting calibration, maintaining or changing equipment, strengthening
reagent management, rewriting procedures, and retraining staff members.
Conclusions: The causes for PT failures relate mainly to laboratory problems, not
to the PT process itself. Therefore, PT sponsored by the NCCL is an effective
evaluation tool for laboratory performance. Also, laboratories should strive to
improve analytical performance.
PMID- 29955863
TI - Decreased Serum 25-Hydroxyvitamin D in Aging Male Mice Is Associated With Reduced
Hepatic Cyp2r1 Abundance.
AB - The prevalence of vitamin D deficiency, as determined by circulating levels of 25
hydroxycalciferol [25(OH)D], is greater in older individuals compared with the
young. To examine the hypothesis that altered production or inactivation of
25(OH)D contributes to lower circulating levels of 25(OH)D, we measured the serum
levels of parent vitamin D3 (cholecalciferol) and 25(OH)D. We also determined the
relative abundance of transcripts encoding hepatic CYP2R1 and CYP27B1, the
principal 25-hydroxylases, transcripts encoding enzymes that degrade 25(OH)D in
the liver (Cyp3A11) and kidney (Cyp24A1) and transcripts encoding megalin and
cubilin, proteins critical to vitamin D resorption in the kidney in mice at three
different ages. We observed a significant decline in the relative abundance of
Cyp2R1 in the liver with aging (one-way ANOVA, P = 0.0077). Concurrent with the
decrease in mRNA, a significant decline in hepatic CYP2R1 protein (one-way ANOVA
for trend, P = 0.007) and 25(OH)D (one-way ANOVA for trend, P = 0.002) and in the
ratio of 25(OH)D3 to cholecalciferol (one-way ANOVA, P = 0.0003). By contrast,
levels of the transcripts encoding Cyp3a11, Cyp24a1, and Cyp27b1 megalin and
cubilin were unchanged with aging. A significant positive correlation was found
between Cyp2r1 mRNA and 25(OH)D, and a stronger correlation was found between
Cyp2r1 mRNA and the ratio of 25(OH)D3 to cholecalciferol. These results indicate
that decreased expression of CYP2R1 contributes to the reduced serum levels of
25(OH)D in aging.
PMID- 29955862
TI - Duplication of hsp-110 Is Implicated in Differential Success of Globodera Species
under Climate Change.
AB - Managing the emergence and spread of crop pests and pathogens is essential for
global food security. Understanding how organisms have adapted to their native
climate is key to predicting the impact of climate change. The potato cyst
nematodes Globodera pallida and G. rostochiensis are economically important plant
pathogens that cause yield losses of up to 50% in potato. The two species have
different thermal optima that may relate to differences in the altitude of their
regions of origin in the Andes. Here, we demonstrate that juveniles of G. pallida
are less able to recover from heat stress than those of G. rostochiensis. Genome
wide analysis revealed that while both Globodera species respond to heat stress
by induction of various protective heat-inducible genes, G. pallida experiences
heat stress at lower temperatures. We use C. elegans as a model to demonstrate
the dependence of the heat stress response on expression of Heat Shock Factor-1
(HSF-1). Moreover, we show that hsp-110 is induced by heat stress in G.
rostochiensis, but not in the less thermotolerant G. pallida. Sequence analysis
revealed that this gene and its promoter was duplicated in G. rostochiensis and
acquired thermoregulatory properties. We show that hsp-110 is required for
recovery from acute thermal stress in both C. elegans and in G. rostochiensis.
Our findings point towards an underlying molecular mechanism that allows the
differential expansion of one species relative to another closely related species
under current climate change scenarios. Similar mechanisms may be true of other
invertebrate species with pest status.
PMID- 29955864
TI - Association Between the Oligomeric Status of p53 and Clinical Outcomes in Li
Fraumeni Syndrome.
AB - Li-Fraumeni syndrome (LFS) is a rare hereditary cancer disorder with highly
variable clinical outcomes that results from germline mutations in the TP53 gene.
Here we report that the quaternary structure of p53 is an important factor
affecting cellular functions and the clinical outcomes of LFS patients (n = 87).
Specifically, carriers of monomeric p53 mutants (n = 56) exhibited complete
penetrance, with a 2.11-fold greater risk of cancer-related death (95% confidence
interval [CI] = 1.07 to 4.30) and a statistically significantly lower median
survival age as compared with carriers of multimeric (dimeric or tetrameric, n =
31) p53 mutants (33 years, 95% CI = 30 to 50, vs 51 years, 95% CI = 40 to NA,
respectively, two-sided P = .03), who presented incomplete penetrance. Cellular
functional assays using p53-null H1299 cells expressing clinically relevant p53
mutants confirmed that the cellular effects observed upon loss of p53
oligomerization are associated with clinical outcomes of LFS patients. The
association between p53 oligomeric state and clinical phenotype suggests that
TP53 mutations are not all equivalent and supports the implementation of new
genotype-adapted guidelines for the management of LFS patients with TP53
mutations in the oligomerization domain.
PMID- 29955866
TI - Reasons for Opioid Discontinuation and Unintended Consequences Following Opioid
Discontinuation Within the TOPCARE Trial.
AB - Objective: To identify reasons for opioid discontinuation and post
discontinuation outcomes among patients in the Transforming Opioid Prescribing in
Primary Care (TOPCARE) study. Design: In TOPCARE, an intervention to improve
adherence to opioid prescribing guidelines, randomized intervention primary care
providers (PCPs) received nurse care manager support, an electronic registry,
academic detailing, and electronic tools, and control PCPs received electronic
tools only. Setting: Four Boston safety net primary care practices. Subjects:
Patients in both TOPCARE study arms who discontinued opioid therapy during the
trial. Methods: Through chart review, we examined the reason for discontinuation
and post-discontinuation outcomes: one or more PCP visits, one or more pain
related emergency department (ED) visits, evidence of opioid use disorder (OUD),
and referral for OUD treatment. Results: Opioid discontinuations occurred in
83/586 (14.2%) intervention and 42/399 (10.5%) control patients (P = 0.09). Among
patients who discontinued opioids, 81 (65%) discontinued for misuse, with no
difference by group (P = 0.38). Aberrancy in monitoring (e.g., discordant urine
drug test results) was the most common type of misuse prompting discontinuation
(occurring in (51/83 [61%] of intervention patients vs 19/42 [45%, P = 0.08] of
control patients). Intervention patients who discontinued opioids had less PCP
follow-up (65% vs 88%, P < 0.01) compared with control patients. We found no
differences between groups for pain-related ED visits, evidence of OUD, or OUD
treatment referral following discontinuation. Conclusions: The decreased follow
up among TOPCARE intervention patients who discontinued opioids highlights the
need to understand unintended consequences of involuntary opioid discontinuations
resulting from interventions to reduce opioid risk.
PMID- 29955867
TI - Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus.
AB - Context: Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4
monoclonal antibody used in cancer immunotherapy. It targets the programmed cell
death-1 (PD-1) receptor, which is important in maintaining self-tolerance.
However, immune checkpoint blockade is associated with a risk for immune-related
adverse events (irAEs) potentially affecting the endocrine organs. Type 1
diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Evidence Acquisition: Systematic search of four databases (MEDLINE, Embase, Web
of Science, and Cochrane Library) using the search terms "diabetes" or
"ketoacidosis" and "pembrolizumab," "nivolumab," "PD-1 inhibitor," or
"immunotherapy." Included were articles published in English between 1 January
2012 and 1 January 2018. The search was supplemented by bibliographic searches of
the complete reference lists of all included papers. Evidence Synthesis: We
provide an overview of all published cases (n = 42) of PD-1 inhibitor-induced
type 1 diabetes mellitus to date, including a well-characterized case of islet
cell antibody and glutamic acid decarboxylase antibody-positive diabetes
mellitus, in a patient with a diabetes-prone HLA genotype. She presented with
diabetic ketoacidosis during pembrolizumab therapy for a metastatic uveal
melanoma. Furthermore, we discuss potential pathogenic mechanisms, clinical
presentation, prognostic markers (beta-cell antibodies and HLA type), treatment,
and a screening protocol. Conclusions: Because the use of immunotherapy will
increase, it is essential that all clinicians are aware of diabetic ketoacidosis
as a rare and life-threatening side effect of immunotherapy. Blood glucose
monitoring during anti-PD-1 therapy is necessary.
PMID- 29955865
TI - Global Study of Social Odor Awareness.
AB - Olfaction plays an important role in human social communication, including
multiple domains in which people often rely on their sense of smell in the social
context. The importance of the sense of smell and its role can however vary inter
individually and culturally. Despite the growing body of literature on
differences in olfactory performance or hedonic preferences across the globe, the
aspects of a given culture as well as culturally universal individual differences
affecting odor awareness in human social life remain unknown. Here, we conducted
a large-scale analysis of data collected from 10 794 participants from 52 study
sites from 44 countries all over the world. The aim of our research was to
explore the potential individual and country-level correlates of odor awareness
in the social context. The results show that the individual characteristics were
more strongly related than country-level factors to self-reported odor awareness
in different social contexts. A model including individual-level predictors
(gender, age, material situation, education, and preferred social distance)
provided a relatively good fit to the data, but adding country-level predictors
(Human Development Index, population density, and average temperature) did not
improve model parameters. Although there were some cross-cultural differences in
social odor awareness, the main differentiating role was played by the individual
differences. This suggests that people living in different cultures and different
climate conditions may still share some similar patterns of odor awareness if
they share other individual-level characteristics.
PMID- 29955868
TI - Comment on: Hydroxychloroquine-induced retinal toxicity in an asymptomatic
patient.
PMID- 29955869
TI - Sodium intake and blood pressure in children and adolescents: a systematic review
and meta-analysis of experimental and observational studies.
AB - Background: High sodium intake is a cause of elevated blood pressure in adults.
In children and adolescents, less evidence is available and findings are
equivocal. We systematically reviewed the evidence from experimental and
observational studies on the association between sodium intake and blood pressure
in children and adolescents. Methods: A systematic search of the Medline, Embase,
CINAHL and CENTRAL databases up to March 2017 was conducted and supplemented by a
manual search of bibliographies and unpublished studies. Experimental and
observational studies involving children or adolescents between 0 and 18 years of
age were included. Random-effects meta-analyses were performed by pooling data
across all studies, separately for experimental and observational studies, and
restricting to studies with sodium intake and blood pressure measurement methods
of high quality. Subgroup meta-analyses, sensitivity analyses and meta
regressions were conducted to investigate sources of heterogeneity and
confounding. The dose-response relationship was also investigated. Results: Of
the 6572 publications identified, 85 studies (14 experimental; 71 observational,
including 60 cross-sectional, 6 cohort and 5 case-control studies) with 58 531
participants were included. In experimental studies, sodium reduction
interventions decreased systolic blood pressure by 0.6 mm Hg [95% confidence
interval (CI): 0.5, 0.8] and diastolic blood pressure by 1.2 mm Hg (95% CI: 0.4,
1.9). The meta-analysis of 18 experimental and observational studies (including
3406 participants) with sodium intake and blood pressure measurement methods of
high quality showed that, for every additional gram of sodium intake per day,
systolic blood pressure increased by 0.8 mm Hg (95% CI: 0.4, 1.3) and diastolic
blood pressure by 0.7 mm Hg (95% CI: 0.0, 1.4). The association was stronger
among children with overweight and with low potassium intake. A quasi-linear
relationship was found between sodium intake and blood pressure. Conclusions:
Sodium intake is positively associated with blood pressure in children and
adolescents, with consistent findings in experimental and observational studies.
Since blood pressure tracks across the life course, our findings support the
reduction of sodium intake during childhood and adolescence to lower blood
pressure and prevent the development of hypertension.
PMID- 29955870
TI - Is it time to reconsider the role of irinotecan for the treatment of high-grade
gliomas?
PMID- 29955871
TI - Quality of care for cardiovascular disease prevention in rheumatoid arthritis:
compliance with hyperlipidemia screening guidelines.
AB - Objective: To evaluate compliance with hyperlipidaemia screening guidelines for
cardiovascular disease prevention in RA compared with the general population.
Methods: We conducted a longitudinal study of a population-based RA cohort
including all prevalent cases in British Columbia between 1996 and 2006, followed
up until 2010, with matched general population controls. Using administrative
data, we measured compliance with general population guidelines (testing lipids
every 5 years for women ?50 and men ?40), after excluding individuals with
previous diabetes, coronary artery disease or hyperlipidaemia. Compliance was
measured as the proportion of 5-year eligibility periods with one or more lipid
test. Compliance rates in RA and controls were compared by Chi-square test. Odds
ratio (95% CI) of compliance in RA (vs controls) was estimated using generalized
estimating equation models, adjusting for age and sex. Mean compliance rate per
patient was also calculated and compared using Mann-Whitney U test. Results:
Analyses included 5587 RA individuals and 5613 controls, contributing 6993 and
7208 5-year eligibility periods, respectively. Lipids were measured in 56.6 and
59.5% of eligibility periods in RA and controls, respectively [adjusted odds
ratio (95% CI): 0.97 (0.90, 1.06)]. Screening improved over time in RA relative
to the general population, but remained suboptimal even after 2003, at 65.8%.
Mean (s.d.) compliance rate per patient was 56.6 (47.2)% for RA and 59.5 (46.6)%
for controls. Family physicians ordered almost all the lipid tests. Conclusion:
Compliance with general population guidelines for hyperlipidaemia screening in RA
was poor and did not differ from the general population, despite a higher risk of
cardiovascular diseases.
PMID- 29955872
TI - Regulating Alternative Healing in France, and the Problem of 'Non-Medicine'.
AB - This article explores the ambiguities of the legal system that, in France,
regulates 'alternative healing', and determines the boundaries of legitimate
medical care. While the law suggests that the delivery of therapeutic care should
be the monopoly of biomedically-trained professionals, alternative healers
operate very widely, and very openly, in France. They practice, however, on the
verge of (il)legality, often organising their activities, individually and
collectively, so as to limit the likelihood of state intervention. This creates a
high degree of precarity for both practitioners and, crucially, for patients.
Efforts to change the system are being deployed, but while healers themselves
have increasingly organised to seek recognition by the state, alternative healing
occupies an uncertain policy space: they are not fully constituted as a social
and policy matter by the state, and occupy a liminal position between medicine
and spirituality that "unsettles" republican ideals of scientific rationality,
and of secularism. This article explores some of those tensions, at the crossroad
between law, science, and medicine. It reflects on why tensions seem to persist
around the regulatory questions at stake, and suggests that ways forward may
depend on moving away from science as a sole arbiter in drawing boundaries of
legitimate and illegitimate care in regulation.
PMID- 29955874
TI - Good training, systems and funding, not good luck: what hematologists and
oncologists believe would make it easier for them to refer their cancer patients
to psychosocial care.
AB - Rates of referral of patients to psychosocial services are low in most cancer
treatment centers, while rates of distress are high. The purpose of this study is
to identify clinicians' barriers to referring cancer patients to psychosocial
services and strategies that could increase rates of referral. A purposive
sampling method ensured data were gathered in two large public teaching hospitals
from seven oncologists and five hematologists with varying levels of experience,
of whom five were female. Data were collected using semistructured interviews
guided by the Capability, Opportunity, Motivation and Behavior model (Michie S,
Atkins L, West R. The Behaviour Change Wheel: A Guide to Designing Interventions.
United Kingdom: Silverback Publishing; 2014.). This helped us to identify
modifiable variables associated with referral likelihood and associated evidence
based strategies using the Behavior Change Wheel. Data were analyzed using
Thematic Analysis. Barriers relating to capability, opportunity, and motivation
to refer to psychosocial services were identified, including lack of knowledge of
available services, how to refer to them, and the types of patients who would
benefit. Other barriers included the following: lack of time to discuss and
refer, convoluted referral pathways, long waiting times, and fear of patient
reluctance due to stigma. Respondents identified numerous strategies for
overcoming barriers, including training on referral best practice, role-plays,
the provision of lists of services with referral and contact details, and
increasing service capacity via additional funding. Findings inform the
development of acceptable, evidence-based strategies, to improve rates of
referral to psychosocial services by oncologists and hematologists. Without
implementation, a substantial number of people affected by cancer will continue
to suffer from potentially treatable distress.
PMID- 29955873
TI - Evolution on the Biophysical Fitness Landscape of an RNA Virus.
AB - Viral evolutionary pathways are determined by the fitness landscape, which maps
viral genotype to fitness. However, a quantitative description of the landscape
and the evolutionary forces on it remain elusive. Here, we apply a biophysical
fitness model based on capsid folding stability and antibody binding affinity to
predict the evolutionary pathway of norovirus escaping a neutralizing antibody.
The model is validated by experimental evolution in bulk culture and in a drop
based microfluidics that propagates millions of independent small viral
subpopulations. We demonstrate that along the axis of binding affinity, selection
for escape variants and drift due to random mutations have the same direction, an
atypical case in evolution. However, along folding stability, selection and drift
are opposing forces whose balance is tuned by viral population size. Our results
demonstrate that predictable epistatic tradeoffs between molecular traits of
viral proteins shape viral evolution.
PMID- 29955875
TI - Defining malaria risk: it is not only about epidemiology but also about
perception and risk threshold of travellers and policy makers.
PMID- 29955877
TI - The risk of alopecia areata and other related autoimmune diseases in patients
with sleep disorders: a Korean population-based retrospective cohort study.
AB - Study Objectives: The aim of our study was to investigate the risk of alopecia
areata occurrence in patients with sleep disorders. Methods: This study was a
retrospective cohort study based on the National Health Insurance Service
National Sample Cohort database of patients with a sleep disorder, along with age
and sex-matched control subjects from 2003 to 2013. The hazard ratio (HR) of
alopecia areata was compared between the patients with sleep disorders and
control subjects adjusting comorbid diseases which could affect the incidence of
alopecia areata. We also compared the prevalence of comorbid diseases in the
patients with sleep disorders and control subjects. Results: Among the 25,800
patients with sleep disorders and the 129,000 control subjects, patients with
sleep disorders were at a significantly increased risk for alopecia areata when
compared with control subjects (adjusted HR 1.651 [95% CI 1.382-1.974]),
especially in younger age groups (0-24 and 25-44 years). In a multivariate
logistic analysis, sleep disorders were not only associated with alopecia areata
(OR 1.913 [95% CI 1.717-2.171]), but also with other comorbid diseases, including
solid-organ cancers (OR 1.099 [95% CI 1.049-1.151]), Graves' disease (OR 1.717
[95% CI 1.562-1.886]), Hashimoto thyroiditis (OR 1.641 [95% CI 1.413-1.905]),
vitiligo (OR 1.539 [95% CI 1.236-1.917]), and rheumatoid arthritis (OR 1.886 [95%
CI 1.780-1.998]). Conclusions: This study demonstrated that sleep disorder is an
independent risk factor for alopecia areata, especially in individuals under the
age of 45 years old.
PMID- 29955876
TI - MBNL splicing activity depends on RNA binding site structural context.
AB - Muscleblind-like (MBNL) proteins are conserved RNA-binding factors involved in
alternative splicing (AS) regulation during development. While AS is controlled
by distribution of MBNL paralogs and isoforms, the affinity of these proteins for
specific RNA-binding regions and their location within transcripts, it is
currently unclear how RNA structure impacts MBNL-mediated AS regulation. Here, we
defined the RNA structural determinants affecting MBNL-dependent AS activity
using both cellular and biochemical assays. While enhanced inclusion of MBNL
regulated alternative exons is controlled by the arrangement and number of MBNL
binding sites within unstructured RNA, when these sites are embedded in a RNA
hairpin MBNL binds preferentially to one side of stem region. Surprisingly,
binding of MBNL proteins to RNA targets did not entirely correlate with AS
efficiency. Moreover, comparison of MBNL proteins revealed structure-dependent
competitive behavior between the paralogs. Our results showed that the structure
of targeted RNAs is a prevalent component of the mechanism of alternative
splicing regulation by MBNLs.
PMID- 29955878
TI - Characterization of a new semi-dominant dwarf allele of SLR1 and its potential
application in hybrid rice breeding.
AB - The widespread introduction of semi-dwarf1 (sd1), also known as the 'Green
Revolution' gene, has dramatically increased rice yield. However, the extensive
use of limited sources of dwarf genes may cause 'bottleneck' effects in breeding
new rice varieties. Alternative dwarf germplasms are quite urgent for rice
breeding. Here, we characterized a new allele of the rice Slr1-d mutant, Slr1-d6,
which reduced plant height by 37%, a much milder allele for dwarfism. Slr-d6 was
still responsive to gibberellin (GA) to a reduced extent. The mutation site in
Slr1-d6 was less conserved in the TVHYNP domain, leading to the specific semi
dominant dwarf phenotype. Expression of SLR1 and five key GA biosynthetic genes
was disturbed in Slr1-d6, and the interaction between Slr1-d6 and GID1 was
decreased. In the genetic background of cultivar 9311 with sd1 eliminated, Slr1
d6 homozygous plants were ~70 cm tall. Moreover, Slr1-d6 heterozygous plants were
equivalent in height to the standard sd1 semi-dwarf 9311, but with a 25% yield
increase, showing its potential application in hybrid rice breeding.
PMID- 29955879
TI - Long-Term Care Residents' Geriatric Syndromes at Admission and Disablement over
Time: An Observational Cohort Study.
AB - Background: Disablement occurs when people lose their ability to perform
activities of daily living (ADLs) like bathing and dressing, and is measured as
the rate of increasing disability over time. We examined whether balance
impairment, cognitive impairment or pain among residents at admission to long
term care homes were predictive of their rate of disablement over the subsequent
two years. Methods: Linked administrative databases were used to conduct a
longitudinal cohort study of 12,334 residents admitted to 633 long-term care
(LTC) homes between April 1st 2011 and March 31st 2012, in Ontario, Canada.
Residents received an admission assessment of disability upon admission to LTC
using the RAI-MDS 2.0 ADL long-form score (ADL LFS, range 0 - 28) and at least
two subsequent disability assessments. Multivariable regression models estimated
the adjusted association between balance impairment, cognitive impairment and
pain present at admission and residents' subsequent disablement over two years.
Results: This population sample of newly admitted Ontario long-term care
residents had a median disability score of 13 (IQR= 7, 19) at admission. Greater
balance impairment and cognitive impairment at admission were significantly
associated with faster resident disablement over two years in adjusted models,
while daily pain was not. Conclusions: Balance impairment and cognitive
impairment among newly admitted LTCH residents are associated with increased rate
of disablement over the following two years. Further research should examine the
mechanisms driving this association and identify whether they are amenable to
intervention.
PMID- 29955880
TI - Bird-like propagating brain activity in anesthetized Nile crocodiles.
AB - Study Objectives: The changes in electroencephalogram (EEG) activity that
characterize sleep and its sub-states-slow-wave sleep (SWS) and rapid eye
movement (REM) sleep-are similar in mammals and birds. SWS is characterized by
EEG slow waves resulting from the synchronous alternation of neuronal membrane
potentials between hyperpolarized down-states with neuronal quiescence and
depolarized up-states associated with action potentials. By contrast, studies of
non-avian reptiles report the presence of high-voltage sharp waves (HShW) during
sleep. How HShW relate to EEG phenomena occurring during mammalian and avian
sleep is unclear. We investigated the spatiotemporal patterns of
electrophysiological phenomena in Nile crocodiles (Crocodylus niloticus)
anesthetized with isoflurane to determine whether they share similar
spatiotemporal patterns to mammalian and avian slow waves. Methods: Recordings of
anesthetized crocodiles were made using 64-channel penetrating arrays with
electrodes arranged in an 8 * 8 equally spaced grid. The arrays were placed in
the dorsal ventricular ridge (DVR), a region implicated in the genesis of HShW.
Various aspects of the spatiotemporal distribution of recorded signals were
investigated. Results: Recorded signals revealed the presence of HShW resembling
those reported in earlier studies of naturally sleeping reptiles. HShW propagated
in complex and variable patterns across the DVR. Conclusions: We demonstrate that
HShW within the DVR propagate in complex patterns similar to those observed for
avian slow waves recorded from homologous brain regions. Consequently, sleep with
HShW may represent an ancestral form of SWS, characterized by up-states occurring
less often and for a shorter duration than in mammals and birds.
PMID- 29955881
TI - Reidentification and antifungal susceptibility profile of Candida guilliermondii
and Candida famata clinical isolates from a culture collection in Argentina.
AB - The aim of this work was to reidentify strains previously identified as Candida
guilliermondii and Candida famata by conventional phenotypic methods conserved in
a culture collection from Argentina using ribosomal DNA sequencing, ACT1 gene
sequencing, and matrix-assisted laser desorption ionization - time of flight mass
spectrometry (MALDI-TOF MS). In addition, we performed antifungal susceptibility
tests of eight antifungal drugs commonly used in clinical treatment. We
identified 68 isolates belonging to the Candida guilliermondii species complex
(59 C. guilliermondii, 8 C. fermentati, and 1 Candida carpophila), 16 isolates
belonging to the Candida famata species complex (8 C. famata, 6 Debaryomyces
nepalensis, 1 Debaryomyces fabryi, and 1 Debaryomyces tyrocola). Although
sequencing of ITS region was able to identify C. guilliermondii and D. nepalensis
isolates, sequencing of ACT1 gene seems to be the most appropriate technique for
differentiation between C. fermentati and C. carpophila and between members of
the C. famata species complex others than D. nepalensis. MALDI-TOF MS has a good
potential for the identification of these yeasts, particularly in clinical
laboratories since is a rapid and easy to perform technique. Here, we report the
first isolation of D. tyrocola from a human patient and the first isolation of D.
nepalensis from lungs and blood of human patients. Finally, correct
identification and determination of antifungal susceptibility of those closely
related species could be a useful tool for clinicians to choose the most
effective antifungal treatment.
PMID- 29955882
TI - Factors Associated With Participation in Cardiac Episode Payments Included in
Medicare's Bundled Payments for Care Improvement Initiative.
AB - Importance: Medicare's Bundled Payments for Care Improvement (BPCI) is a
voluntary pilot program evaluating bundled payments for several common
cardiovascular conditions. Evaluating the external validity of this program is
important for understanding the effects of bundled payments on cardiovascular
care. Objective: To determine whether participants in BPCI cardiovascular bundles
are representative of US acute care hospitals and identify factors associated
with participation. Design, Setting, and Participants: Retrospective cross
sectional study of hospitals participating in BPCI model 2 bundles for acute
myocardial infarction (AMI), congestive heart failure (CHF), coronary artery
bypass graft, and percutaneous coronary intervention and nonparticipating control
hospitals (October 2013 to January 2017). The BPCI participants were identified
using data from the Centers for Medicare and Medicaid Services, and controls were
identified using the 2013 American Hospital Association's Survey of US Hospitals.
Hospital structural characteristics and clinical performance data were obtained
from the American Heart Association survey and Centers for Medicare and Medicaid
Services. One hundred fifty-nine hospitals participating in BPCI model 2 cardiac
bundles and 1240 nonparticipating control hospitals were compared, and a
multivariable logistic regression was estimated to identify predictors of BPCI
participation. Exposures: Bundled payments. Main Outcomes and Measures: Hospital
level structural characteristics and 30-day risk-adjusted readmission and
mortality rates for AMI and CHF. Results: Compared with nonparticipants, BPCI
participants were larger, more likely to be privately owned or teaching
hospitals, had lower Medicaid bed day ratios (ratio of Medicaid inpatient days to
total inpatient days: 17.0 vs 19.3; P < .001), and were less likely to be safety
net hospitals (2.5% vs 12.3%; P < .001). The BPCI participants had higher AMI and
CHF discharge volumes, were more likely to have cardiac intensive care units and
catheterization laboratories, and had lower risk-standardized 30-day mortality
rates for AMI (13.7% vs 16.6%; P = .001) and CHF (11.3 vs 12.4; P = .005). In
multivariable analysis, larger hospital size and access to a cardiac
catheterization laboratory were positively associated with participation. Being a
safety net hospital was negatively associated with participation (odds ratio,
0.3; 95% CI, 0.1-0.7; P = .001). Conclusions and Relevance: Hospitals
participating in BPCI model 2 cardiac bundles differed in significant ways from
nonparticipating hospitals. The BPCI outcomes may therefore have limited external
validity, particularly among small and safety net hospitals with limited clinical
cardiac services.
PMID- 29955884
TI - Return to work after occupational and non-occupational lower extremity
amputation.
AB - Background: Factors impacting on return to work (RTW) after lower extremity
amputation are important in occupational rehabilitation. Aims: Our objective was
to compare RTW in patients who had traumatic work-related amputation with
amputations from other causes. Methods: A retrospective cohort study was
conducted with participants employed at the time of amputation and at least 1
year post-discharge from amputee rehabilitation. The primary outcome measure was
RTW. Results: One hundred and forty-seven amputees were included with 69%
returning to work. Amputation reason did not impact on RTW (odds ratio [OR] 1.83,
P = non-significant). Trans-femoral amputees were less likely to RTW (OR 0.22, P
< 0.05). Years since amputation (OR 1.20, P = 0.001) and Reintegration to Normal
Living Index (OR 1.05, P < 0.001) were predictive of RTW after adjusting for
other covariates. Conclusions: Amputation aetiology did not impact on RTW. Years
since amputation, level of amputation and Return to Normal Living Index were
associated with RTW which may be important to consider in RTW prognosis and
planning.
PMID- 29955883
TI - Antenna proton sensitivity determines photosynthetic light harvesting strategy.
AB - Photoprotective non-photochemical quenching (NPQ) represents an effective way to
dissipate the light energy absorbed in excess by most phototrophs. It is often
claimed that NPQ formation/relaxation kinetics are determined by xanthophyll
composition. We, however, found that, for the alveolate alga Chromera velia, this
is not the case. In the present paper, we investigated the reasons for the
constitutive high rate of quenching displayed by the alga by comparing its light
harvesting strategies with those of a model phototroph, the land plant Spinacia
oleracea. Experimental results and in silico studies support the idea that fast
quenching is due not to xanthophylls, but to intrinsic properties of the Chromera
light harvesting complex (CLH) protein, related to amino acid composition and
protein folding. The pKa for CLH quenching was shifted by 0.5 units to a higher
pH compared with higher plant antennas (light harvesting complex II; LHCII). We
conclude that, whilst higher plant LHCIIs are better suited for light harvesting,
CLHs are 'natural quenchers' ready to switch into a dissipative state. We propose
that organisms with antenna proteins intrinsically more sensitive to protons,
such as C. velia, carry a relatively high concentration of violaxanthin to
improve their light harvesting. In contrast, higher plants need less violaxanthin
per chlorophyll because LHCII proteins are more efficient light harvesters and
instead require co-factors such as zeaxanthin and PsbS to accelerate and enhance
quenching.
PMID- 29955885
TI - Wellness coaches in intervention delivery: pediatric asthma as an example.
AB - Asthma is the most common chronic illness among children, and parental
psychosocial stress is a well-documented mediator of poor pediatric asthma
outcomes. However, few interventions have targeted parental stress as a means for
improving child asthma outcomes. The purpose of the study is to describe the
feasibility and acceptability of the use of wellness coaches in a parent-focused
stress management intervention in pediatric asthma. Data on the feasibility of
wellness coach recruitment and training, intervention delivery and fidelity, and
acceptability are provided from a randomized controlled trial intervention group
sample of 107 African American parents of children aged 4-12 years (M = 6.6
years) with persistent asthma. Implementation of intervention strategies is
described. Two wellness coaches were recruited and trained, and they conducted
the four-session intervention for the study. The majority (79%) of possible
intervention sessions were completed. The fidelity ratings of coach
implementation of the intervention were high and indicated that 92%-95% of target
intervention content was covered during the sessions. Participants reported high
acceptability of working with the wellness coaches. Use of wellness coaches in a
parent-focused stress management pediatric asthma intervention was feasible and
acceptable. Using wellness coaches for parent interventions may be applicable
across other pediatric conditions and has the potential to change clinical
practice.
PMID- 29955886
TI - Evaluation of the Taking Texas Tobacco Free Workplace Program within behavioral
health centers.
AB - Despite the health benefits of tobacco control and cessation initiatives, tobacco
users with behavioral health disorders (BHDs) have less access to evidence-based
tobacco dependence treatment. Academic-community partnerships can help guide the
translation of tobacco-related research findings and evidence-based guidelines
into real-world applications. Through a comprehensive, evidence-based,
multilevel, and multicomponent program, Taking Texas Tobacco Free (TTTF)
facilitated the implementation of tobacco-free workplaces at 18 local mental
health authorities in Texas, comprising over 250 individual community behavioral
health centers. Compared with preprogram implementation, key accomplishments
postimplementation include: (1) educated over 5,000 employees (nonclinical staff
and providers) on the hazards of tobacco use and benefits of quitting,
particularly among people with BHD; providers were additionally trained on the
use of evidence based practices (EBPs; i.e. 5A's model, use of pharmacotherapy)
to identify and treat tobacco use among people with BHD; (2) providers'
significant increase in conducting tobacco-use assessments and using EBPs; (3)
significant decrease in nonclinical staff tobacco use; (4) increase in quit
attempts among consumers as evidenced by the demand for nicotine replacement
therapy; and (5) reach to over 115,000 community members through outreach and
education about the benefits of quitting tobacco use and maintaining a healthy
lifestyle. TTTF demonstrated that the implementation of a comprehensive tobacco
free workplace program in behavioral health settings is feasible and beneficial,
facilitating the capacity building of healthcare professionals and enhancing
their resulting engagement in EBPs, and promoting healthier lifestyles among
employees, consumers, and community members as a whole.
PMID- 29955887
TI - Marburg and Ravn Viruses Fail to Cause Disease in the Domestic Ferret (Mustela
putorius furo).
AB - The domestic ferret was recently described as a uniformly lethal model for 3
species of Ebolavirus. More importantly, this new model utilizes nonadapted wild
type Ebolaviruses. Here, in a proof-of-concept study, we infected ferrets with
different variants of the closely related Marburg and Ravn viruses using
different doses and routes of exposure. Although ferrets produced a neutralizing
humoral response to challenge, we did not observe disease or viremia in any
animal. The lack of disease in ferrets underscores the notion that differential
mechanisms to immunity among filoviruses exist and may provide a model to better
understand how differences contribute to disease.
PMID- 29955888
TI - Human aging and longevity are characterized by high levels of mitokines.
AB - Mitochondrial stress elicits the production of stress response molecules
indicated as mitokines, including FGF21, GDF15 and Humanin (HN). Many diseases
are characterized by progressive mitochondrial dysfunction with alterations of
mitokine secretion. It is still controversial whether healthy aging and extreme
longevity are accompanied by altered production of mitokines. We analyzed FGF21,
HN and GDF15 plasma levels in 693 subjects aged from 21 to 113 years, and the
association of these mitokines with parameters of health status. FGF21, HN and
GDF15 resulted increased in old age, with the highest levels found in
centenarians. These molecules are associated with worsened parameters (such as
handgrip strength, insulin sensitivity, total triglycerides), particularly in 70
year-old persons, and their levels are inversely correlated with survival in the
oldest subjects. Considering the positive biological effect of these molecules,
our results can be interpreted in the framework of the hormetic paradigm as an
attempt of the cells/tissues to cope with a stress that can have beneficial or
detrimental effects depending on its intensity. Finally, persons with Down
Syndrome (characterized by accelerated aging) have higher levels of GDF15 and HN
with respect to their siblings, suggesting that these molecules, especially
GDF15, could be considered markers of biological age.
PMID- 29955889
TI - Web-based versus in-person methods for training lay community health advisors to
implement health promotion workshops: participant outcomes from a cluster
randomized trial.
AB - Project HEAL (Health through Early Awareness and Learning) is an implementation
trial that compared two methods of training lay peer community health advisors
(CHAs)-in-person ("Traditional") versus web-based ("Technology")-to conduct a
series of three evidence-based cancer educational workshops in African American
churches. This analysis reports on participant outcomes from Project HEAL.
Fifteen churches were randomized to the two CHA training methods and the
intervention impact was examined over 24 months. This study was conducted in
Prince George's County, MD, and enrolled 375 church members age 40-75.
Participants reported on knowledge and screening behaviors for breast, prostate,
and colorectal cancer. Overall, cancer knowledge in all areas increased during
the study period (p < .001). There were significant increases in digital rectal
exam (p < .05), fecal occult blood test (p < .001), and colonoscopy (p < .01) at
24 months; however, this did not differ by study group. Mammography maintenance
(56% overall) was evidenced by women reporting multiple mammograms within the
study period. Participants attending all three workshops were more likely to
report a fecal occult blood test or colonoscopy at 24 months (p < .05) than those
who attended only one. These findings suggest that lay individuals can receive
web-based training to successfully implement an evidence-based health promotion
intervention that results in participant-level outcomes comparable with (a)
people trained using the traditional classroom method and (b) previous efficacy
trials. Findings have implications for resources and use of technology to
increase widespread dissemination of evidence-based health promotion
interventions through training lay persons in community settings.
PMID- 29955890
TI - Active periodic electrograms in remote monitoring of pacemaker recipients: the
PREMS study.
AB - Aims: Remote monitoring (RM) is considered as a standard of care for pacemaker
recipients. Remote monitoring systems provide calendar-based intracardiac
electrogram recordings (IEGM) only with the current pacemaker settings (passive
IEGM). PREMS (Pacemaker Remote Electrogram Monitoring Study), an observational,
multicentre trial, prospectively evaluated the clinical value of an active IEGM
(aIEGM), including three 10-s sections (passive IEGM, encouraged sensing, and
encouraged pacing), compared to other RM data and to its passive IEGM section.
Secondary objectives included the added value of the aIEGM to fully assess the
sensing and pacing functions of each lead. Methods and results: Patients were
enrolled within 3 months after pacemaker implantation and followed until the
first transmitted aIEGM, which was analysed together with all other RM data. In
total, 567 patients were enrolled (79 +/- 9 years, 62% men, 19% single-chamber,
and 81% dual-chamber pacemakers). Of 547 aIEGMs transmitted in 547 patients, 161
[29.4%; 95% confidence interval (95% CI) 25.6-33.3%] indicated at least one
anomaly non-detectable with certainty-or at all-on other RM data, including
atrial arrhythmia, extrasystoles, undersensing, oversensing, and loss of capture.
In 21.7% of cases the detected events deserved a corrective action. The sensing
and pacing function of each lead could be fully assessed in 77.3% of aIEGM (95%
CI 72.6-82.0%) vs. 15.5% (95% CI 11.4-19.6%) when considering only the passive
IEGM section (P < 0.001). Conclusion: An active IEGM improves the clinical value
of remote pacemaker follow-up. Furthermore, compared to a passive IEGM, the aIEGM
increases the capability to fully assess remotely the sensing and pacing
functions.
PMID- 29955891
TI - Human Biomarkers of Outcome Following Rift Valley Fever Virus Infection.
AB - Rift Valley fever virus is an arbovirus found in Africa and the Middle East. Most
infected individuals experience a mild self-limiting illness; however, some
develop severe disease including hepatitis, hemorrhagic fever, or encephalitis.
The biological reasons for these marked differences in disease manifestation are
unknown. In this study, we evaluate 32 biomarkers in serum of 26 patients from an
outbreak that occurred in Saudi Arabia in 2000-2001. Eleven biomarkers correlated
with viral RNA. Thirteen biomarkers were associated with a fatal outcome. No
associations of biomarkers and hemorrhage or central nervous system disease were
identified in this cohort.
PMID- 29955893
TI - Synthesis-dependent repair of Cpf1-induced double strand DNA breaks enables
targeted gene replacement in rice.
AB - The recently developed CRISPR (clustered regularly interspaced short palindromic
repeats)/Cpf1 system expands the range of genome editing and is emerging as an
alternative powerful tool for both plant functional genomics and crop
improvement. Cpf1-CRISPR RNA (crRNA) produces double strand DNA breaks (DSBs)
with long 5'-protruding ends, which may facilitate the pairing and insertion of
repair templates through homology-directed repair (HDR) for targeted gene
replacement and introduction of the desired DNA elements at specific gene loci
for crop improvement. However, the potential mechanism underlying HDR of DSBs
generated by Cpf1-crRNA remains to be investigated, and the inherent low
efficiency of HDR and poor availability of exogenous donor DNA as repair
templates strongly impede the use of HDR for precise genome editing in crop
plants. Here, we provide evidence of synthesis-dependent repair of Cpf1-induced
DSBs, which enables us precisely to replace the wild-type ALS gene with the
intended mutant version that carries two discrete point mutations conferring
herbicide resistance to rice plants. Our observation that the donor repair
template (DRT) with only the left homologous arm is sufficient for precise
targeted allele replacement offers a better understanding of the mechanism
underlying HDR in plants, and greatly simplifies the design of DRTs for precision
genome editing in crop improvement.
PMID- 29955892
TI - How to create state-of-the-art genetic model systems: strategies for optimal
CRISPR-mediated genome editing.
AB - Model systems with defined genetic modifications are powerful tools for basic
research and translational disease modelling. Fortunately, generating state-of
the-art genetic model systems is becoming more accessible to non-geneticists due
to advances in genome editing technologies. As a consequence, solely relying on
(transient) overexpression of (mutant) effector proteins is no longer recommended
since scientific standards increasingly demand genetic modification of endogenous
loci. In this review, we provide up-to-date guidelines with respect to homology
directed repair (HDR)-mediated editing of mammalian model systems, aimed at
assisting researchers in designing an efficient genome editing strategy.
PMID- 29955895
TI - High-Dimensional Immunology for Schizophrenia Research: A Short Perspective.
AB - There is evidence that many diseases are accompanied by immunological
perturbations and even when the perturbations are not directly pathogenic, they
can provide correlative signatures of pathology that can be useful
diagnostically. For example, the neuromuscular disease, multiple sclerosis, has a
pathophysiology that is immunologically mediated, evinced by the use of
increasingly sophisticated immunosuppression therapy and by animal studies in
which many of the symptoms can be reproduced by breaking immunological tolerance
to myelin basic protein. By contrast, immunological correlates exist for other
diseases, such as schizophrenia, but it is not clear which, if any, are
causative. The problem is compounded in that genome-wide association studies have
shown strong genetic correlation between schizophrenia and bipolar disorder,
moderate correlation with schizophrenia and major depressive disease, and low
correlation with autism spectrum disorders, yet schizophrenia and autism spectrum
disorders share immunological signatures. This example illustrates the problem of
ferreting out specific, and hopefully causal, immunological correlates with
schizophrenia that differentiate it from genetically or immunologically related
psychiatric disorders. Fortunately, recent advances in systems immunology provide
potent tools to tackle this problem. This review will illustrate these tools by
recent examples and sketch out possible pathways to use them for identification
of schizophrenia-specific immunological correlates.
PMID- 29955894
TI - KAP1 facilitates reinstatement of heterochromatin after DNA replication.
AB - During cell division, maintenance of chromatin features from the parental genome
requires their proper establishment on its newly synthetized copy. The loss of
epigenetic marks within heterochromatin, typically enriched in repetitive
elements, endangers genome stability and permits chromosomal rearrangements via
recombination. However, how histone modifications associated with heterochromatin
are maintained across mitosis remains poorly understood. KAP1 is known to act as
a scaffold for a repressor complex that mediates local heterochromatin formation,
and was previously demonstrated to play an important role during DNA repair.
Accordingly, we investigated a putative role for this protein in the replication
of heterochromatic regions. We first found that KAP1 associates with several DNA
replication factors including PCNA, MCM3 and MCM6. We then observed that these
interactions are promoted by KAP1 phosphorylation on serine 473 during S phase.
Finally, we could demonstrate that KAP1 forms a complex with PCNA and the histone
lysine methyltransferase Suv39h1 to reinstate heterochromatin after DNA
replication.
PMID- 29955896
TI - Inherited Metabolic Disorders: Implications for the Obstetrician-Gynecologist.
AB - Importance: Inherited metabolic disorders, or inborn errors of metabolism, can
result in significant morbidity and mortality. Advances in genetic testing,
including newborn screening and prenatal carrier screening, continue to increase
awareness and highlight the importance of these conditions. Increasingly, women
born with these conditions are surviving to adulthood, and many become pregnant.
The practicing obstetrician-gynecologist should be familiar with the most common
and the most relevant inherited metabolic disorders affecting women. Objective:
The objective of this review is to define inherited metabolic disorders that have
relevance to the obstetrician-gynecologist. We discuss the diagnosis,
presentation, epidemiology, and special concerns to the obstetrician-gynecologist
managing patients affected by these conditions. Evidence Acquisition: A MEDLINE
search of "inherited metabolic disorders" and "inborn errors of metabolism" and
specific conditions reported in the review was performed. Results: The evidence
cited in this review includes 8 case reports or case series, 4 text books, 1
systematic review, 1 American College of Obstetricians and Gynecologists
committee opinion, and 18 additional peer-reviewed journal articles that were
original research or expert opinion summaries. Conclusions and Relevance:
Inherited metabolic disorders manifest in diverse ways that have clinical
implications for the obstetrician-gynecologist. Knowledge of these disorders and
their pathophysiology and genetic basis can improve care provided for women
affected by this diverse group of conditions. It is critical to assemble a
multidisciplinary team of providers to optimize care for patients with inherited
metabolic disorders.
PMID- 29955897
TI - Preterm Premature Rupture of Membranes: A Review of 3 National Guidelines.
AB - Importance: Preterm premature rupture of membranes (PPROM) is a major cause of
perinatal mortality and morbidity. Objective: The aim of this study was to
compare recommendations from published national guidelines for pregnancies
complicated with PPROM. Evidence Acquisition: A descriptive review of 3 national
guidelines on PPROM was performed: the Royal College of Obstetricians and
Gynaecologists on "Preterm Prelabour Rupture of Membranes," the American College
of Obstetricians and Gynecologists on "Premature Rupture of Membranes," and the
Society of Obstetricians and Gynaecologists of Canada on "Antibiotic Therapy in
Preterm Premature Rupture of the Membranes." Guidelines were compared in the
diagnosis and management of PPROM. Recommendations and strength of evidence were
reviewed based on each guideline's method of reporting. The references were
compared with regard to their total number, total number of randomized controlled
trials, Cochrane reviews, and systematic reviews/meta-analyses cited. Results:
The variations stated on the guidelines reflect the heterogeneity of the
literature contributing to the guidelines and challenges of diagnosing and
managing cases of PPROM. Conclusions: An improved international guideline may
improve safety and outcomes in pregnant women with PPROM.
PMID- 29955898
TI - Correlated Selection on Amino Acid Deletion and Replacement in Mammalian Protein
Sequences.
AB - A low ratio of nonsynonymous and synonymous substitution rates (dN/dS) at a codon
is an indicator of functional constraint caused by purifying selection.
Intuitively, the functional constraint would also be expected to prevent such a
codon from being deleted. However, to the best of our knowledge, the correlation
between the rates of deletion and substitution has never actually been estimated.
Here, we use 8595 protein-coding region sequences from nine mammalian species to
examine the relationship between deletion rate and dN/dS. We find significant
positive correlations at the levels of both sites and genes. We compared our data
against controls consisting of simulated coding sequences evolving along
identical phylogenetic trees, where deletions occur independently of
substitutions. A much weaker correlation was found in the corresponding simulated
sequences, probably caused by alignment errors. In the real data, the
correlations cannot be explained by alignment errors. Separate investigations on
nonsynonymous (dN) and synonymous (dS) substitution rates indicate that the
correlation is most likely due to a similarity in patterns of selection rather
than in mutation rates.
PMID- 29955899
TI - 5-HT3 antagonists decrease discounting rate without affecting sensitivity to
reward magnitude in the delay discounting task in mice.
AB - RATIONALE: Impulsive choice has often been evaluated in rodents according to the
proportion of choices for the delayed large magnitude reinforcer (%large choice)
in a delay-discounting task (DDT). However, because %large choice is influenced
by both sensitivity to reinforcer magnitude and sensitivity to delayed
reinforcement (i.e., discounting rate), distinctively evaluating such discounting
parameters represents a critical issue demanding methods to determine each
parameter in rats. The serotonin (5-HT) system is well known to be involved in
impulsive choice; nevertheless, only a few studies have distinguished discounting
parameters and investigated how 5-HT modulators affect discounting rate.
OBJECTIVE: Here, we performed a discounting parameter analysis in mice and
examined the effects of various 5-HT modulators on discounting rate. METHODS: We
set up DDTs with different delay schedules to determine which schedule could
address delay-discounting rates in mice. We examined the effect of the following
drugs on impulsive choice: a 5-HT reuptake inhibitor (paroxetine), a 5-HT1A
receptor agonist (8-OH-DPAT), and two 5-HT3 receptor antagonists (granisetron and
ondansetron). RESULTS: Mice showed typical delay discounting at the shorter delay
schedules (up to 4 s delay). The %large choice under shorter, but not longer,
schedules followed an exponential function and allowed us to derive discounting
rates. We selected a DDT with a 4-s delay schedule for further experiments.
Granisetron and ondansetron, but not paroxetine or 8-OH-DPAT, decreased
discounting rates without affecting sensitivity to reinforcer magnitude.
CONCLUSION: We found that a method to calculate discounting rates in rats is also
applicable to mouse models. We also provided evidence that 5-HT3 antagonism
controls impulsive choice in mice.
PMID- 29955900
TI - Baseline prepulse inhibition of the startle reflex predicts the sensitivity to
the conditioned rewarding effects of cocaine in male and female mice.
AB - RATIONALE: Prepulse inhibition (PPI) of the startle reflex is a model of pre
attentional inhibitory function. The dopamine baseline in the nucleus accumbens
plays a key role in PPI regulation as well as in the rewarding effects of
cocaine. OBJECTIVES: The aim of this study was to evaluate the predictive ability
of PPI to identify the more vulnerable mice of both sexes to the conditioned
rewarding effects of cocaine. METHODS: Male and female OF1 mice were first tested
in the PPI paradigm to classify them as high or low PPI. Afterwards, they were
evaluated in the conditioned place preference (CPP) paradigm induced by cocaine
(1, 6 and 12 mg/kg). Moreover, the D1R and D2R protein expressions in the
striatum of high and low PPI animals were analysed by Western blot. RESULTS: Only
high-PPI mice acquired CPP induced by low doses of cocaine (1 and 6 mg/kg), while
the low-PPI mice needed a higher dose of cocaine (12 mg/kg) to acquire the CPP,
but once mice were conditioned, males did not extinguish the conditioned
preference and females reinstated the preference with lower doses of cocaine than
their control counterparts. Low-PPI animals, especially females, showed higher
basal levels of D2R than those with a higher PPI. CONCLUSIONS: Low-PPI mice
presented a lower sensitivity to the conditioned rewarding effects of cocaine,
but once they were conditioned with a higher dose, they displayed a stronger,
perseverant conditioned preference. The predictive capacity of PPI to detect the
more vulnerable mice to the conditioned effects of cocaine is discussed.
PMID- 29955901
TI - Trimetazidine protects against myocardial ischemia/reperfusion injury by
inhibiting excessive autophagy.
AB - : Trimetazidine (TMZ) has been demonstrated to have protective effects against
myocardial ischemia/reperfusion (MI/R) injury. In the present study, we
investigated the effects and the underlying mechanisms of TMZ on autophagy during
MI/R in vivo and in vitro. In the in vivo study, an animal model of MI/R was
induced by coronary occlusion. TMZ (20 mg/kg/day) protected the rat hearts from
MI/R-induced heart failure by increasing ejection fraction and fractional
shortening and decreasing end-systolic volume, end-diastolic volume, left
ventricular (LV) internal diameter at systole, and LV internal diameter at
diastole; it alleviated myocardial injury and oxidative stress by decreasing LDH,
creatine kinase MB isoenzyme, ROS, and MDA levels and increasing SOD and
glutathione peroxidase levels in plasma. TMZ also reduced myocardial infarct size
and apoptosis. Moreover, TMZ markedly inhibited MI/R-induced autophagy by
decreasing the protein and messenger RNA levels of LC3-II, Beclin1, ATG5, and
ATG7 and the number of autophagosomes and by involving the AKT/mTOR pathway.
Further, in the in vitro experiments, H9c2 cells were incubated with TMZ (40 MUM)
to explore the direct effects of TMZ following exposure to hypoxia and
reoxygenation (H/R). TMZ increased cell viability and the concentration of
intracellular SOD and inhibited H/R-induced cell apoptosis and ROS production.
Moreover, TMZ decreased the number of autophagosomes and autophagy-related
protein expression; it also upregulated p-AKT and p-mTOR expression. In addition,
TMZ augmented Bcl-2 protein expression and diminished Bax protein expression, the
Bax/Bcl-2 rate, and cleaved caspase-3 level. However, these effects on H9c2 cells
were notably abolished by the PI3K inhibitor LY294002. In conclusion, our results
showed that TMZ inhibited I/R-induced excessive autophagy and apoptosis, which
was, at least partly, mediated by activating the AKT/mTOR pathway. KEY MESSAGES:
TMZ improved cardiac function, alleviated myocardial injury and oxidative stress,
and reduced the myocardial infarct area and apoptosis. TMZ inhibited MI/R-induced
myocardial autophagy, H/R-induced H9c2 cell apoptosis, and autophagy flux. The
effect of TMZ on autophagy was repressed by LY294002. TMZ protected against MI/R
injury by inhibiting excessive autophagy via activating the AKT/mTOR pathway.
PMID- 29955903
TI - Radiographic appearance and clinical significance of fidget spinner ingestions.
AB - BACKGROUND: According to anecdotal press reports, there have been medically
significant ingestions of fidget spinner toys, including ingestions that required
endoscopic intervention. Fidget spinners have been marketed to improve attention
and have been suggested as a therapeutic alternative to medications in children
with attention deficit hyperactivity disorder (ADHD). OBJECTIVE: To describe the
radiographic appearance and features of ingested fidget spinner components. To
evaluate clinical significance via rates of endoscopic intervention, incidence in
patients on ADHD medications, and mean age compared to other accidental foreign
body ingestions. MATERIALS AND METHODS: A nested retrospective case control study
analyzed pediatric accidental foreign body ingestions identified via electronic
medical record search between March 1, 2017, and Feb. 28, 2018. Radiographic
identifiability, component type and maximum diameter of ingested fidget spinner
components were described. A nested cohort of non-fidget spinner ingestions
between May 1 and Aug. 31, 2017, was compared with the fidget spinner ingestions
for rates of endoscopic intervention (a), concomitant use of ADHD medication (b)
and mean age (c) using the Fisher exact test (a and b) and independent samples t
test (c). RESULTS: There were 1,095 unintentional foreign body ingestions. Ten
were ingested fidget spinner component ingestions. Eight of the 10 ingested
components were radiographically identifiable. Compared with the nested cohort of
non-fidget spinner ingestions, fidget spinner ingestions were more likely to
undergo endoscopic intervention (P=0.009, 5/10 fidget spinner ingestions vs.
54/383 other ingestions). Fidget spinner patients were more likely to be on ADHD
medication (P=0.011, 2/10 fidget spinners vs. 5/383 other). Fidget spinner mean
patient age was significantly older than other ingestions (P=0.015, mean: 7.1
years fidget spinner ingestions vs. 4.0 years for other ingestions). CONCLUSION:
Compared with other foreign body ingestions, patients who ingested fidget spinner
components were more likely to undergo endoscopic intervention, had a higher rate
of ADHD medication use and were older. Familiarity with the radiographic
appearance of ingested fidget spinner components is important for patient
management.
PMID- 29955904
TI - Lung and airway shape in neuroendocrine cell hyperplasia of infancy.
AB - BACKGROUND: Neuroendocrine cell hyperplasia of infancy (NEHI) is a rare lung
disease associated with significant air trapping. Although chest CT is crucial in
establishing a diagnosis, CT and biopsy findings do not reveal airway
abnormalities to explain the air trapping. OBJECTIVE: We compared lung and airway
morphology obtained from chest CT scans in children with NEHI and control
children. In the children with NEHI, we explored relationships between lung and
airway shape and lung function. MATERIALS AND METHODS: We performed a
retrospective review of children with NEHI who underwent clinical chest CT. We
identified control children of similar size and age. We created lung masks and
airway skeletons using semi-automated software and compared them using
statistical shape modeling methods. Then we calculated a logistic regression
model using lung and airway shape to differentiate NEHI from controls, and we
compared shape model parameters to lung function measurements. RESULTS: Airway
and lung shapes were statistically different between children with NEHI and
controls. We noted a broad lung apex in the children with NEHI and a
significantly increased apical anterior-posterior lung diameter. A logistic
regression model including lung shape was 90% accurate in differentiating
children with NEHI from controls. Correlation coefficients were significant
between lung function values and lung and airway shape. CONCLUSION: Lung and
airway shapes were different between children with NEHI and control children in
this cohort. Children with NEHI had an increased anteroposterior diameter of
their lungs that might be useful in the diagnostic criteria.
PMID- 29955902
TI - Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model
exposed to rotenone.
AB - To date, most in vitro toxicity testing has focused on acute effects of compounds
at high concentrations. This testing strategy does not reflect real-life
exposures, which might contribute to long-term disease outcome. We used a 3D
human dopaminergic in vitro LUHMES cell line model to determine whether effects
of short-term rotenone exposure (100 nM, 24 h) are permanent or reversible. A
decrease in complex I activity, ATP, mitochondrial diameter, and neurite
outgrowth were observed acutely. After compound removal, complex I activity was
still inhibited; however, ATP levels were increased, cells were electrically
active and aggregates restored neurite outgrowth integrity and mitochondrial
morphology. We identified significant transcriptomic changes after 24 h which
were not present 7 days after wash-out. Our results suggest that testing short
term exposures in vitro may capture many acute effects which cells can overcome,
missing adaptive processes, and long-term mechanisms. In addition, to study
cellular resilience, cells were re-exposed to rotenone after wash-out and
recovery period. Pre-exposed cells maintained higher metabolic activity than
controls and presented a different expression pattern in genes previously shown
to be altered by rotenone. NEF2L2, ATF4, and EAAC1 were downregulated upon single
hit on day 14, but unchanged in pre-exposed aggregates. DAT and CASP3 were only
altered after re-exposure to rotenone, while TYMS and MLF1IP were downregulated
in both single-exposed and pre-exposed aggregates. In summary, our study shows
that a human cell-based 3D model can be used to assess cellular adaptation,
resilience, and long-term mechanisms relevant to neurodegenerative research.
PMID- 29955905
TI - Inhibition of SRC family kinases facilitates anti-CTLA4 immunotherapy in head and
neck squamous cell carcinoma.
AB - The immune system plays a critical role in the establishment, development, and
progression of head and neck squamous cell carcinoma (HNSCC). As treatment with
single-immune checkpoint agent results in a lower response rate in patients, it
is important to investigate new strategies to maintain favorable anti-tumor
immune response. Herein, the combination immunotherapeutic value of CTLA4
blockade and SFKs inhibition was assessed in transgenic HNSCC mouse model. Our
present work showed that tumor growth was not entirely controlled when HNSCC
model mice were administered anti-CTLA4 chemotherapeutic treatment. Moreover, it
was observed that Src family kinases (SFKs) were hyper-activated and lack of anti
tumor immune responses following anti-CTLA4 chemotherapeutic treatment. We
hypothesized that activation of SFKs is a mechanism of anti-CTLA4 immunotherapy
resistance. We, therefore, carried out combined drug therapy using anti-CTLA4
mAbs and an SFKs' inhibitor, dasatinib. As expected, dasatinib and anti-CTLA4
synergistically inhibited tumor growth in Tgfbr1/Pten 2cKO mice. Furthermore,
dasatinib and anti-CTLA4 combined to reduce the number of myeloid-derived
suppressor cells and Tregs, increasing the CD8+ T cell-to-Tregs ratio. We also
found that combining dasatinib with anti-CTLA4 therapy significantly attenuated
the expression of p-STAT3Y705 and Ki67 in tumoral environment. These results
suggest that combination therapy with SFKs inhibitors may be a useful therapeutic
approach to increase the efficacy of anti-CTLA4 immunotherapy in HNSCC.
PMID- 29955906
TI - [Why do we need cardiac arrest centers?]
AB - In patients with out-of-hospital cardiac arrest (OHCA) and return of spontaneous
circulation (ROSC) following cardiopulmonary resuscitation (CPR), the prognosis
is influenced by various factors. In the prehospital setting, the duration of
ischemia from the time of onset of cardiac arrest to the beginning of effective
resuscitation measures is by far the most critical and determining factor for
outcome. This interval can be shortened by an increase in the rate of lay CPR
measures. With respect to intrahospital follow-up care, a number of structural
factors have a relevant influence on prognosis. According to the literature, case
volume, size of the hospital and the number of post-OHCA patients treated per
year also have a large influence on the further prognosis. The crucial factor
here is the availability and permanent readiness of a catheterization laboratory
with the possibility of an immediate coronary intervention. In OHCA patients with
ST-segment elevation myocardial infarction (STEMI), the time passed until the
reopening of the occluded infarcted vessel is of paramount importance for
survival. The 24/7 around the clock availability of a catheterization laboratory
is therefore one of the indispensable prerequisites for a cardiac arrest center
(CAC). In addition, a number of technical, structural, and organizational
arrangements must be implemented in the CAC clinics in order to fulfil the
requirements for such a center. The certification of CACs is currently being
implemented by the German Resuscitation Council (GRC) and the German Society of
Cardiology (DGK). As an important aim the GRC and the medical societies involved
are hoping to avoid misallocation of post-OHCA patients to the nearest hospital,
which may not be a suitable center for the treatment of these patients. Future
studies will show whether CACs can indeed comprehensively improve the prognosis
of OHCA patients following successful prehospital resuscitation.
PMID- 29955907
TI - Heart failure with mid-range ejection fraction and with preserved ejection
fraction.
AB - The annual "heart report" published by the German Heart Foundation (Deutsche
Herzstiftung) in December 2017 indicates that heart failure (ICD I50) remains the
number one diagnosis of in-hospital-treated patients throughout Germany. For some
time, the clinical diagnosis of heart failure has been verified by
echocardiographic parameters as well as cardiac biomarkers that assist the
clinician to rule in or rule out the presence of a failing heart, when used
wisely. By introducing the term "heart failure with mid-range ejection fraction"
(HFmrEF), the 2016 European Society of Cardiology (ESC) heart failure guidelines
established a third heart failure entity, which was not necessarily seen as an
improvement by the heart failure community. Nevertheless, half of all patients
suffering from heart failure are now classified as having HFmrEF or heart failure
with preserved ejection fraction (HFpEF), but the etiology and treatment options
differ substantially. To elucidate this issue, the current review aims to
highlight the key findings published to date. This should minimize the confusion
that may have been generated by the new term "HFmrEF".
PMID- 29955908
TI - Bone metabolism, density, and geometry in postmenopausal women with vitamin D
insufficiency: a cross-sectional comparison of the effects of elevated
parathyroid levels.
AB - : Increased levels of parathyroid hormone (PTH) may have adverse effects on bone
health. In a cross-sectional design, we investigated this hypothesis among 102
postmenopausal vitamin D insufficient women. Elevated PTH was associated with
altered bone geometry, decreased bone mineral density in the spine, and increased
bone turnover. INTRODUCTION: In vitamin D insufficiency, elevated parathyroid
hormone (PTH) levels may contribute to adverse effect on bone. We assessed
effects of PTH responses to vitamin D insufficiency on bone metabolism, density,
and geometry. METHODS: Using a cross-sectional design, we investigated 102
healthy postmenopausal women with low 25-hydroxy-vitamin D (< 50 nmol/L) levels,
who had either secondary hyperparathyroidism with elevated PTH levels (> 6.9
pmol/L, N = 51) or normal PTH levels (N = 51). Bone mineral density (BMD) and
bone geometry were assessed by Dual-Energy X-ray absorptiometry (DXA),
quantitative computed tomography (QCT) and high-resolution peripheral QCT
(HRpQCT) scans. Bone metabolism was assessed by biochemistry including bone
turnover markers. RESULTS: Levels of 25(OH)D were 38 (IQR 31-45) nmol/L with no
differences between groups. PTH levels were 8.5 (IQR 7.5-9.5) in women with SHPT
and 5.2 (4.4-6.6) pmol/L in women with normal PTH (p < 0.001). BMI and eGFR did
not differ between groups. SHPT was associated with lower total- and trabecular
bone area, lower cortical perimeter, and increased cortical area in tibia and
radius. SHPT was associated with a lower weight-adjusted BMD at the lumbar spine
(p < 0.05). High compared to normal PTH levels were associated with significantly
lower plasma levels of 1,25(OH)2D, phosphate, but higher levels of osteocalcin
and borderline higher levels of CTx. PTH correlated to osteocalcin and CTx.
CONCLUSIONS: High PTH levels are associated with altered bone geometry, increased
bone turnover, and reduced BMD at the spine. Whether an increased cortical
thickness with a lower trabecular volume is an effect of PTH or not needs further
elucidations.
PMID- 29955909
TI - Developing confidence in basic prescribing skills during medical school: a
longitudinal questionnaire study investigating the effects of a modified clinical
pharmacology course.
AB - PURPOSE: To investigate if increased focus on pharmacotherapy during medical
school can increase students' confidence in basic prescribing skills, that is,
performing medication reviews and writing medication discharge summaries.
METHODS: In 2016, the clinical pharmacology course in medical school in
Gothenburg, Sweden, was modified to facilitate the students' acquisition of
prescribing skills, with (i) clarified learning outcomes; (ii) supply of a list
of common drugs for self-completion; (iii) instructions to practice medication
reviews/discharge summaries during the ward-based education; and (iv) a
concluding compulsory seminar where the students were to present prescribing
related experiences from their ward-based attendance. Questionnaires were
administered to students participating in the course before (2016; n = 101) and
after (2017; n = 137) implementation of the modifications. Students were asked to
grade their agreement from 1 (totally disagree) to 5 (totally agree) on
statements related to their perceived confidence in basic prescribing skills.
RESULTS: In all, 195 students returned the questionnaire (response rate 82%;
median age 24 years; 68% female). Confidence was rated higher after the
modifications were implemented, both regarding medication reviews and medication
discharge summaries, after vs. before 3.6 +/- 1.2 vs. 3.2 +/- 1.0 (P = 0.024),
and 4.3 +/- 0.9 vs. 3.9 +/- 1.1 (P = 0.008), respectively. The adjusted odds for
being confident in performing these tasks were 1.49/1.36 times greater after the
course modifications (P = 0.047/0.019). Perceived confidence in performing
medication reviews/summary reports was positively correlated with numbers
performed (P < 0.0001). CONCLUSIONS: Modifications of the clinical pharmacology
course during medical school, focusing on students' training in pharmacotherapy,
was associated with increased confidence of this core skill for a physician.
PMID- 29955910
TI - Detecting intertrochanteric hip fractures with orthopedist-level accuracy using a
deep convolutional neural network.
AB - OBJECTIVE: To compare performances in diagnosing intertrochanteric hip fractures
from proximal femoral radiographs between a convolutional neural network and
orthopedic surgeons. MATERIALS AND METHODS: In total, 1773 patients were enrolled
in this study. Hip plain radiographs from these patients were cropped to display
only proximal fractured and non-fractured femurs. Images showing pseudarthrosis
after femoral neck fracture and those showing artificial objects were excluded.
This yielded a total of 3346 hip images (1773 fractured and 1573 non-fractured
hip images) that were used to compare performances between the convolutional
neural network and five orthopedic surgeons. RESULTS: The convolutional neural
network and orthopedic surgeons had accuracies of 95.5% (95% CI = 93.1-97.6) and
92.2% (95% CI = 89.2-94.9), sensitivities of 93.9% (95% CI = 90.1-97.1) and 88.3%
(95% CI = 83.3-92.8), and specificities of 97.4% (95% CI = 94.5-99.4) and 96.8%
(95% CI = 95.1-98.4), respectively. CONCLUSIONS: The performance of the
convolutional neural network exceeded that of orthopedic surgeons in detecting
intertrochanteric hip fractures from proximal femoral radiographs under limited
conditions. The convolutional neural network has a significant potential to be a
useful tool for screening for fractures on plain radiographs, especially in the
emergency room, where orthopedic surgeons are not readily available.
PMID- 29955911
TI - [Erratum to: How should urologists perform implantation of subcutaneous central
venous port systems? A single center experience of 347 cases].
PMID- 29955913
TI - Transcatheter Arterial Embolization for Postoperative Bleeding Following
Abdominal Surgery.
AB - PURPOSE: We aimed to estimate the usefulness of transcatheter arterial
embolization (TAE) in patients with postoperative abdominal hemorrhage and to
evaluate the effects of pancreatic fistula on clinical outcomes and angiographic
findings. MATERIALS AND METHODS: We enrolled 22 patients (20 males and 2 females;
mean age 63 years; range 25-86 years), who underwent transarterial angiography
for postoperative hemorrhage after abdominal surgery. This group corresponded to
28 procedures. Technical and clinical success rates were calculated, and clinical
findings and outcomes were compared between patients with and without a
pancreatic fistula. RESULTS: Pre-interventional CT was performed in all patients
before first angiography, and the location of the bleeding was identified in all
but one patient. Active arterial bleeding, identified by extravasation of
contrast agent (n = 12), pseudoaneurysm formation (n = 12), and arterial wall
irregularity (n = 2) were detected in 28 angiographic procedures, and
embolization was performed in 26 instances. Various embolization techniques such
as isolation, packing, embolization, and stentgraft implantation were performed.
The technical and clinical success rates were 96% (25/26 procedures) and 82%
(18/22 patients), respectively. In hemodynamically unstable patients (shock
index: heart rate/systolic blood pressure > 1), a 92% (12/13 cases) technical
success rate was achieved. There were no significant differences in any evaluated
parameters between patients with and without pancreatic fistula. CONCLUSION: TAE
is a safe and effective for treating postoperative hemorrhage even in patients
with hemodynamic instability and pancreatic fistula. Additionally, pre
interventional CT is useful for effective, consecutive interventions.
PMID- 29955914
TI - Biomarker in cardiology : DGK welcomes ESC Munich 2018.
AB - Biomarkers have become essential tools for diagnosis and risk stratification in
cardiology. This update provides an overview on the development and clinical
application of selected biomarkers with a focus on cardiac troponins (cTn). We
will specifically indicate the contribution of members of the German Cardiac
Society to the field both in test development and evaluation as well as
application in clinical care settings. Furthermore, we briefly touch on the
development of novel biomarkers and expanded applications in personalized
medicine and as companion diagnostics.
PMID- 29955915
TI - Patent foramen ovale closure for patients excluded from the randomized
cryptogenic stroke trials.
PMID- 29955916
TI - Patent foramen ovale closure for patients excluded from the randomized
cryptogenic stroke trials: response to letter by Zaman et al.
PMID- 29955917
TI - [Acrally emphasized papules-a case report].
AB - Syringotropic mycosis fungoides (STMF) is an extremely rare form of cutaneous T
cell lymphoma with 51 published cases so far. Clinically STMF is manifested
similarly to folliculotropic mycosis fungoides (MF), whereby the course of STMF
is much milder. Histopathologically, it shows a prominent tropism of the T-cell
lymphocytic infiltrate for the eccrine epithelium. We report the case of a 65
year-old woman with multiple small papules on the feet, shinbones and back.
PMID- 29955919
TI - Endoscopic intact removal of medium-size- or multiple bladder stones with the use
of transvesical laparoendoscopic single-site surgery.
AB - OBJECTIVES: To determine the feasibility and safety of performing transvesical
laparoendoscopic single-site surgery (T-LESS) in patients with medium-size, hard
stones or multiple stones with high burden. METHODS: In this case series study,
12 patients (11 males and one female) with a mean age of 66.8 years were operated
on from February 2016 to May 2017 due to bladder calculi, using the T-LESS
approach with a single-port device (Tri-Port + , Olympus, Germany). Indications
for this procedure were hard, medium-size, solitary stones after previous
unsuccessful endoscopic lithotripsy or the presence of multiple high-burden
stones. In two patients, additional procedures (diverticulectomy or a ureterocele
incision) were performed simultaneously. RESULTS: All stones were removed intact.
No serious complications were observed. The mean operative time was 46 min and
the postoperative hospital stay was 22 h. The mean diameter of the largest stone
and the mean stone volume of each case were 24 mm and 11 cm3, respectively. At
the mean follow-up time of 15 months, there was significant improvement of the
symptoms. CONCLUSIONS: The T-LESS technique is an efficient, safe and minimally
invasive procedure for intact bladder stone removal in selected patients. The
method avoids the risk of urethral injury. Nevertheless, further investigation is
needed to assess the wider applicability of the procedure.
PMID- 29955918
TI - Chitosan oligosaccharides affect xanthone and VOC biosynthesis in Hypericum
perforatum root cultures and enhance the antifungal activity of root extracts.
AB - KEY MESSAGE: Water-soluble chitosan oligosaccharides (COS) affect xanthone and
volatile organic compound content, as well as antifungal activity against human
pathogenic fungi of extracts obtained from Hypericum perforatum root cultures.
Several studies have demonstrated the elicitor power of chitosan on xanthone
biosynthesis in root cultures of H. perforatum. One of the major limitations to
the use of chitosan, both for basic and applied research, is the need to use
acidified water for solubilization. To overcome this problem, the elicitor effect
of water-soluble COS on the biosynthesis of both xanthones and volatile organic
compounds (VOCs) was evaluated in the present study. The analysis of xanthones
and VOCs was performed by HPLC and GC-MS headspace analysis. The obtained results
showed that COS are very effective in enhancing xanthone biosynthesis. With 400
mg L-1 COS, a xanthone content of about 30 mg g-1 DW was obtained. The antifungal
activity of extracts obtained with 400 mg L-1 COS was the highest, with MIC50 of
32 ug mL-1 against Candida albicans and 32-64 ug mL-1 against dermatophytes,
depending on the microorganism. Histochemical investigations suggested the
accumulation of isoprenoids in the secretory ducts of H. perforatum roots. The
presence of monoterpenes and sesquiterpenes was confirmed by the headspace
analysis. Other volatile hydrocarbons have been identified. The biosynthesis of
most VOCs showed significant changes in response to COS, suggesting their
involvement in plant-fungus interactions.
PMID- 29955923
TI - Low-dose corticosteroids and septic shock resolution: implications for randomized
trial design?
PMID- 29955924
TI - Increasing evidence-based interventions in patients with acute infections in a
resource-limited setting: a before-and-after feasibility trial in Gitwe, Rwanda.
AB - OBJECTIVE: To evaluate whether a focused education program and implementation of
a treatment bundle increases the rate of early evidence-based interventions in
patients with acute infections. DESIGN: Single-center, prospective, before-and
after feasibility trial. SETTING: Emergency department of a sub-Saharan African
district hospital. PATIENTS: Patients > 28 days of life admitted to the study
hospital for an acute infection. INTERVENTIONS: The trial had three phases (each
of 4 months). Interventions took place during the second (educational program
followed by implementation of the treatment bundle) and third (provision of
resources to implement treatment bundle) phases. MEASUREMENTS AND MAIN RESULTS:
Demographic, clinical, and laboratory data were collected at study enrollment;
24, 48, and 72 h after hospital admission; and at discharge. A total of 1594
patients were enrolled (pre-intervention, n = 661; intervention I, n = 531;
intervention II, n = 402). The rate of early evidence-based interventions per
patient during Intervention Phase I was greater than during the pre-intervention
phase (74 +/- 17 vs. 79 +/- 15%, p < 0.001). No difference was detected when data
were compared between Intervention Phases I and II (79 +/- 15 vs. 80 +/- 15%, p =
0.58). No differences in the incidence of blood transfusion (pre-intervention,
6%; intervention I, 7%; intervention II, 7%) or severe adverse events in the
first 24 h (allergic reactions: pre-intervention, 0.2%; intervention I, 0%;
intervention II, 0%; respiratory failure: pre-intervention, 2%; intervention I,
2%; intervention II, 2%; acute renal failure: pre-intervention, 2%; intervention
I, 2%; intervention II, 1%) were observed. CONCLUSIONS: Our results indicate that
a focused education program and implementation of an infection treatment bundle
in clinical practice increased the rate of early evidence-based interventions in
patients with acute infections (mostly malaria) admitted to a sub-Saharan African
district hospital. Provision of material resources did not further increase this
rate. While no safety issues were detected, this could be related to the very low
disease severity of the enrolled patient population (
http://www.clinicaltrials.gov : NCT02697513).
PMID- 29955925
TI - Spongiibacterium fuscum sp. nov., a marine Flavobacteriaceae isolated from the
hard coral Galaxea fascicularis.
AB - A novel marine bacterium, designated 04OKA-3-218T, was isolated from the hard
coral Galaxea fascicularis L. collected in Japan. The strain was dark-brown
pigmented, Gram-negative, strictly aerobic, curved-rod-shaped and non-motile.
Phylogenetic analysis based on the 16S rRNA gene sequence showed the affiliation
of the isolate with members of the family Flavobacteriaceae of the phylum
Bacteroidetes, with the highest sequence similarity (95.2%) to Spongiibacterium
pacificum SW169T. The DNA G+C content was 42.9 mol%; MK-6 was the major
menaquinone; with iso-C17:0 3-OH (28.8%), iso-C15:0 (26.8%) and iso-C15:1 H
and/or C13:0 3-OH (21.2%) as the main (> 10%) cellular fatty acids. The major
polar lipid profile consisted of phosphatidylethanolamine, two unidentified
aminolipids, two unidentified phosphoaminolipids and three unidentified lipids.
On the basis of distinct phylogenetic and phenotypic evidences, the strain
represents a novel species of the genus Spongiibacterium, for which the name
Spongiibacterium fuscum sp. nov. is proposed. The type strain of S. fuscum sp.
nov. is 04OKA-3-218T (= KCTC 62504T = NBRC 113248T).
PMID- 29955926
TI - Biofilm and planktonic bacterial communities in a drinking water distribution
system supplied with untreated groundwater.
AB - It is known that both disinfection and water quality can influence the bacterial
communities in a drinking water distribution system (DWDS). Here, we hypothesized
that bacterial communities in a DWDS with untreated groundwater with no prior
purification and disinfection might differ from those in a DWDS with disinfected
surface water. The present study applied Illumina MiSeq sequencing to investigate
biofilm and planktonic bacterial communities in a DWDS fed with untreated
groundwater (receiving no prior purification and disinfection). Considerable
differences in bacterial richness (Chao1 richness estimator: 389-745 for water
and 392-485 for biofilm), diversity (Shannon diversity index: 2.70-3.77 for water
and 2.53-3.66 for biofilm) and community structure existed among both DWDS waters
and biofilms. Biofilm and planktonic bacterial communities had distinct
structures. The service time of DWDS could affect biofilm bacterial richness,
diversity and community structure. Moreover, planktonic bacterial diversity and
community structure might be influenced by NO2- concentration, while planktonic
bacterial richness was related to NO3- concentration. Proteobacteria dominated in
both biofilm and planktonic bacterial communities. Higher concentrations of NO2-
favored the deltaproteobacterial proportion, but lowered the gammaproteobacterial
proportion in drinking water. Overall, our study indicates that bacterial
communities in a DWDS could be influenced by a variety of factors, such as
habitats (water or biofilm), DWDS service time, and water chemistry.
PMID- 29955927
TI - The subjective components of the Disease Activity Score 28-joints (DAS28) in
rheumatoid arthritis patients and coexisting fibromyalgia.
AB - To determine the contribution of fibromyalgia (FM) to the subjective components
of the Disease Activity Score 28-joints (DAS28) in patients with rheumatoid
arthritis (RA), and to analyse the discriminatory performance of the derived
DAS28 patient-reported components (DAS28-P) to identify patients with
fibromyalgic RA. Consecutive RA patients underwent clinical and clinimetric
assessment. The DAS28-P index was derived from the components of the DAS28 scores
by rearranging the DAS28-ESR formula. Patients were distinguished by the presence
of FM. Student parametric t tests or Mann-Whitney non-parametric U tests were
used to determine any between-group differences. Receiver operating
characteristic (ROC) curve analysis was used to test the ability of the DAS28-P
index to distinguish patients with RA and those with fibromyalgic RA. The study
involved 292 RA patients (80.5% females, mean age 63 years) with a mean disease
duration of 11.6 +/- 8.5 years. Forty-three patients (14.7%) had concomitant FM,
and significantly higher tender joint count (p < 0.001), pain numerical rating
scale, global health status (p = 0.007), and DAS28 scores (p = 0.006) than those
without FM. The DAS28-P values were also significantly higher in the patients
with FM (0.68 +/- 0.09 vs 0.58 +/- 0.06; p < 0.001). The discriminatory power of
the DAS28-P was very good (area under the ROC of 0.858, optimal cut-off value of
0.631). The presence of FM strongly influences the DAS28 results. The assessment
of patient-reported components to the DAS28 through the DAS28-P can be a useful
way to identify patients with fibromyalgic RA.
PMID- 29955930
TI - Increased knee laxity with hamstring tendon autograft compared to patellar tendon
autograft: a cohort study of 5462 patients with primary anterior cruciate
ligament reconstruction.
AB - PURPOSE: To compare anterior knee laxity and patient-reported outcome measures
(PROMs) between anterior cruciate ligament reconstruction (ACLR) performed with
bone-patellar tendon-bone (BPTB) and hamstring tendon (HT) autografts and,
moreover, to study any correlation between postoperative anterior knee laxity and
PROMs. METHODS: Patients who underwent primary ACLR at Capio Artro Clinic,
Stockholm, Sweden, from January 2000 to October 2015, were identified in our
local database. Instrumented laxity measurements and PROMs were reviewed. The KT
1000 arthrometer, with an anterior tibial load of 134-N, was used to evaluate
knee laxity preoperatively and at the 6-month follow-up. The Lysholm score was
collected preoperatively and at 6 months postoperatively. The Knee injury and
Osteoarthritis Outcome Score (KOOS) was collected preoperatively and at the 1
year follow-up. RESULTS: A total of 5462 primary ACLRs, 692 BPTBs and 4770 HT
autografts were included in the study. All the patients showed a significant
reduction in knee laxity from preoperatively to postoperatively (BPTB group: from
3.8 +/- 2.6 to 1.2 +/- 2.1 mm; HT group: from 3.6 +/- 3.1 to 1.8 +/- 2.2 mm; P <
0.001 for both). The HT group showed a significantly increased postoperative knee
laxity compared with the BPTB group (1.8 +/- 2.2 vs 1.2 +/- 2.1 mm; P < 0.001).
The mean anterior tibial translation (ATT) reduction from preoperative to
postoperative was significantly larger for the BPTB graft compared with the HT
graft (2.7 +/- 2.2 vs 1.7 +/- 2.6 mm; P < 0.001). A significantly higher rate of
"surgical failures", defined as a postoperative side-to-side (STS) difference > 5
mm, was found in the HT group compared with the BPTB group at follow-up (4.3 vs
2.4%; P < 0.001). A significantly larger improvement was found in the HT group
compared with the BPTB group for the KOOS Pain (9.5 vs 8.0; P = 0.02), Activities
of Daily Living (7.2 vs 5.7; P = 0.006), Sports (24.2 vs 15.3; P < 0.001) and
Quality of Life (25.8 vs 22.1; P = 0.001) subscales. No significant difference
regarding the mean improvement in the Lysholm knee score was found between the
two grafts (BPTB group: 14.5, HT group: 14.0; n.s.). No correlation between
postoperative anterior knee laxity and PROMs was found in either graft group.
CONCLUSION: Primary ACLR performed with HT autograft resulted in greater
postoperative anterior knee laxity and significantly more surgical failures (STS
> 5 mm) compared with BPTB autograft. The BPTB autograft showed a larger anterior
knee laxity reduction (ATT reduction) in conjunction with primary ACLR. The HT
autograft led to a significantly larger improvement in four of five KOOS
subscales from preoperatively to the 1-year follow-up, compared with BPTB
autograft. There was no association between postoperative anterior knee laxity
and PROMs for either graft. The findings of the present study provide clinicians
with valuable information regarding differences in knee laxity and subjective
knee function between BPTB and HT autograft after primary ACLR. The use of BPTB
autograft should be considered for patients with high knee stability demands.
LEVEL OF EVIDENCE: Retrospective cohort study, Level III.
PMID- 29955931
TI - Arthroscopic anterior inferior iliac spine decompression does not alter
postoperative muscle strength.
AB - PURPOSE: The purpose of this study was to assess the additional effect of
anterior inferior iliac spine (AIIS) decompression on knee extensor and hip
flexor strength and compare functional outcomes after arthroscopic FAI correction
with and without AIIS decompression. METHODS: Sixty patients who underwent
arthroscopic FAI correction surgery were divided into two groups matched for AIIS
morphology: 31 patients who underwent arthroscopic FAI surgery only (without AIIS
decompression) (FAI group) (AIIS Type I; n = 5, Type II; n = 26, Type III; n = 0)
and 29 patients who underwent arthroscopic FAI surgery with AIIS decompression
(AIIS group) (AIIS Type I; n = 5, Type II; n = 24, Type III; n = 0). Knee
extensor and hip flexor strength were evaluated preoperatively and at 6 months
after surgery. Patient-reported outcome (PRO) scores using the modified Harris
hip score (MHHS), the nonarthritic hip score (NAHS) and iHOT-12 were obtained
preoperatively and at 6 months after surgery. RESULTS: In the AIIS group, there
was no significant difference between knee extensor strength pre- and
postoperatively (n.s.). In the AIIS group, hip flexor strength was significantly
improved postoperatively compared to preoperative measures (p < 0.05). In the FAI
group, there were no significant improvements regarding muscle strength (n.s.).
While there were no significant differences of preoperative and postoperative
MHHS and NAHS between both groups (MHHS; n.s., NAHS; n.s.), the mean
postoperative iHOT-12 in the FAI group was inferior to that in the AIIS group. (p
< 0.01). The revision surgery rate for the AIIS group was significantly lower
compared with that in the FAI group (p < 0.05). CONCLUSION: Anterior inferior
iliac spine decompression, as a part of an arthroscopic FAI corrective procedure,
had a lower revision surgery rate and did not compromise knee extensor and hip
flexor strength, and it improved clinical outcomes comparable to FAI correction
without AIIS decompression. AIIS decompression for FAI correction improved
postoperative PRO scores without altering the muscle strength of hip flexor and
knee extensor. LEVEL OF EVIDENCE: III.
PMID- 29955929
TI - The lack of standardized outcome measures following lower extremity injury in
elite soccer: a systematic review.
AB - PURPOSE: Sport-specific, performance-based outcomes are increasingly used to
improve evaluation of treatment efficacy in elite athletes; however, its usage in
elite soccer may be limited. The purpose of this investigation is to (1) assess
current outcome reporting in elite soccer; (2) identify any variability in
reporting of outcomes; and (3) determine how sport-specific performance-based
outcomes are utilized to assess treatment efficacy in elite soccer. METHODS: A
systematic review of the Pubmed, MEDLINE, and Embase, Scopus, SportDiscus, CINAHL
and HealthSource: Nursing databases was performed without limitation on
publication year. Inclusion criteria were (1) reporting of outcomes after a (2)
lower extremity injury in (3) elite soccer players. The study's population, type
of injury, return to play, as well as functional, objective, and sport-specific
performance-based outcomes were extracted from each article. The methodological
index for nonrandomized studies was used for quality assessment. RESULTS: Twenty
one studies were selected after application of the inclusion and exclusion
criteria. Objective outcomes were reported by 6 (29%) studies, and 6 (29%)
employed patient-reported outcomes. The visual analog scale, Lysholm, and Tegner
scores were the most common patient-reported outcomes (PROs). Return to play was
reported by 18 (86%) studies, and only 2 (10%) utilized sport-specific
performance-based outcomes. Despite the majority of studies reporting return to
play, variation was seen in the definitions, and 15 (71%) studies reported the
activity level of the players at final follow-up. CONCLUSION: Assessment of
treatment efficacy is limited in elite athletes, and PROs lack the sensitivity to
identify residual performance deficits after an injury. Although performance
based measures are available at the elite level, these outcomes were seldom used
for evaluation of treatment efficacy. CLINICAL RELEVANCE: When treating elite
soccer players, patient-reported outcome measures lack the sensitivity to detect
changes in patient function, thus performance-based metrics may be more
efficacious in assessing return from injury in these patients. LEVEL OF EVIDENCE:
IV.
PMID- 29955932
TI - Vitamin C demand is increased after total knee arthroplasty: a double-blind
placebo-controlled-randomized study.
AB - PURPOSE: This study was designed to determine whether perioperative
supplementation of vitamin C (VC) improves range of motion (ROM) and reduces the
risk of arthrofibrosis (AF) following total knee arthroplasty (TKA). METHODS:
Ninety-five patients undergoing TKA were randomized to either oral VC (1000 mg
daily) or placebo for 50 days (48 VC group, 47 placebo group). The effect of VC
supplementation was tested on ROM, AF, WOMAC, FJS-12, and VC plasma
concentrations (VCc). VCc were analyzed in both patient groups before surgery, 4
and 7 days after surgery. RESULTS: ROM at 1 year was not different between study
groups. The prevalence of AF was 5 of 48 (10.4%) in the VC group compared to 11
of 47 (23.4%) in the placebo group (p = 0.09). VCc decreased post-operatively in
the placebo group (49-12 umol/l on day 7, p < 0.001), but not in the VC group (53
57 umol/l). Patients with a perioperative drop of VCc >= 30 umol/l developed
significantly more AF at 1 year compared to patients with a VCc drop of < 30
umol/l (p = 0.007). CONCLUSIONS: TKA results in VC depletion. Perioperative VC
supplementation prevents VCc drop in most patients undergoing TKA and may lower
the incidence of AF. The clinical relevance of this study is that VC
supplementation seems to be a cheap and safe adjunct to improve functional
outcome after TKA. LEVEL OF EVIDENCE: I. TRIAL REGISTRY: The study was registered
at the ISRCTN registry with study ID ISRCTN40250576.
PMID- 29955933
TI - [Suture techniques for TFCC].
AB - Traumatic ruptures of the triangular fibrocartilaginous complex (TFCC) may cause
ulnar-sided wrist pain. These ruptures frequently lead to instability of the
distal radioulnar joint (DRUJ) because the ulnoradial ligaments, which are
interwoven with the TFCC, are avulsed from the fovea of the ulnar head or-very
rarely-from the radius. Conservative treatment may be sufficient, and some
instability may be tolerated over time. In the case of persistent pain, operative
repair by reattachment of the TFCC and, thereby, the ligaments to the previously
debrided bone in the fovea is effective in reestablishing a stable, pain free
DRUJ. Several arthroscopic and open repair techniques have been described in the
last years. Contraindications such as the ulna-plus-situation or instability due
to even minor degrees of malunion after fractures of the forearm bones must be
kept in mind.An overview is given of the pathological anatomy, diagnosis,
indications and suturing techniques.
PMID- 29955934
TI - Futility of attempts to detect and quantify beta cells by PET imaging in the
pancreas: why it is time to abandon the approach.
AB - In this commentary, we describe the limitations of positron emission tomography
(PET) in visualising and characterising beta cell mass in the native pancreas in
healthy individuals and those diagnosed with diabetes. Imaging with PET requires
a large mass of targeted cells or other structures in the range of approximately
8-10 cm3. Since islets occupy only 1% of the pancreatic volume and are dispersed
throughout the organ, it is our view that uptake of PET tracers, including
[18F]fluoropropyl-(+)-dihydrotetrabenazine, in islets cannot be successfully
detected by current imaging modalities. Therefore, we dispute the feasibility of
PET imaging for the detection of loss of beta cells in the native pancreas in
individuals with diabetes. However, we believe this novel approach can be
successfully employed to visualise beta cell mass in individuals with
hyperinsulinism and transplanted islets.
PMID- 29955935
TI - Engineered commensal bacteria prevent systemic inflammation-induced memory
impairment and amyloidogenesis via producing GLP-1.
AB - The anti-obesity drug GLP-1 has been proven to have an impact on central nervous
system, while its extremely short half-life greatly limited its use. In this
study, our group constructed two engineering strains MG1363-pMG36e-GLP-1 and
VNP20009-pLIVE-GLP-1 to continuously express GLP-1, and supplementation of these
strains, especially MG1363-pMG36e-GLP-1, had significantly restored the spatial
learning and memory impairment of mice caused by LPS (p < 0.05), suppressed glia
activation and Abeta accumulation, and downregulated inflammatory expressions of
COX-2, TLR-4, TNF-a, and IL-1beta. In addition, MG1363-pMG36e-GLP-1 had
significantly blocked the translocation of NF-kappaB signal and inhibited the
phosphorylation of redox-sensitive cytoplasmic signalings of MAPKs and PI3K/AKT.
These data suggest that MG1363-pMG36e-GLP-1 could be used as a safe and effective
nonabsorbed oral treatment for neuroinflammation-related diseases such as
Alzheimer's disease (AD).
PMID- 29955936
TI - Evaluation of the prebiotic potential of arabinoxylans extracted from wheat
distillers' dried grains with solubles (DDGS) and in-process samples.
AB - Distillers' dried grains with solubles (DDGS) is a low-value agro-industrial by
product, rich in arabinoxylans (AX), which is produced by commercial distillery
and bioethanol plants. In a first approach, we investigated the prebiotic
potential of four fractions comprising arabinoxylan oligosaccharides (AXOS) and
xylooligosaccharides (XOS) obtained by enzymatic hydrolysis of AX fractions
derived from DDGS and wet solids (in-process sample of DDGS production process).
Anaerobic batch cultures in controlled pH conditions were used to test the
prebiotic activity of the samples. Results did not show significant differences
between the enzymatic treatments used, and all AXOS/XOS were extensively
fermented after 24 h. In addition, significant increases (P < 0.05) in
Bifidobacterium and total short-chain fatty acids (SCFAs) were observed after 24
h of fermentation. Finally, DDGS-derived hydrolysates were separated on an
anionic semi-preparative column to prepare AXOS/XOS fractions with degree of
polymerisation (DP) greater than 3. Bifidogenic activity and an increase of SCFAs
were again observed after 24 h of fermentation, although this time, the
selectivity was higher and the fermentation slower, suggesting that the
fermentation of this substrate could take place (at least partially) in the
distal part of the colon with highly desirable beneficial effects.
PMID- 29955937
TI - Duplex real-time PCR assay for the simultaneous detection of Caliciopsis pinea
and Fusarium circinatum in pine samples.
AB - Fusarium circinatum and Caliciopsis pinea are the causal agents of Pitch canker
and Caliciopsis canker, respectively. These diseases affect pines and other
conifers both in Europe and North America. The two pathogens cause similar
bleeding cankers, especially at the early stage of colonization. Symptoms closely
resembling those due to F. circinatum can be instead associated with C. pinea.
Since F. circinatum is a quarantine organism, subjected to provisional emergency
measures, its report immediately causes serious economic implications, while C.
pinea, even if now emerging, is not regulated in the EU nor in the USA. For this
reason, a reliable and accurate diagnostic tool able to distinguish between the
two organisms was considered a priority. In this study, we developed and
standardized a duplex real-time PCR assay allowing the simultaneous recognition
of C. pinea and F. circinatum DNA in pine tissue in a reasonably short time and
for amounts as small as 0.06 pg/MUl. The molecular assay is, therefore, able to
detect the infection even before symptoms have fully developed. The test was
challenged with a very large set of strains (110 different isolates) collected in
different regions of the world and host trees, and gave reliable results. The
high efficiency of this method suggests its use as a standard diagnostic tool
during phytosanitary controls. In addition, the duplex real-time PCR assay
presented here is the first DNA-based method designed to detect C. pinea, which
is becoming an increasing threat to pine stands both in North America and in
Europe.
PMID- 29955938
TI - Hypophosphatemia as a Predictor of Organ-Specific Complications Following
Gastrointestinal Surgery: Analysis of 8034 Patients.
AB - BACKGROUND: Organ-specific complications (OSC) remain serious potential sequela
of gastrointestinal surgery. Hypophosphatemia correlates with poor outcomes and
may be a harbinger of OSC after gastrointestinal surgery. Our goal was to
describe and evaluate the relationship between postoperative phosphate levels and
OSC. METHODS: Consecutive patients who underwent pancreatic, colorectal, or
gastric resections were analyzed. OSC were defined as those resulting from the
failure of at least one anastomosis performed during the primary resection,
manifesting as an anastomotic leak, fistula, and/or intra-abdominal abscess.
Postoperative serum phosphate levels and other recognized OSC risk factors were
compared among patients who did and did not develop OSC. RESULTS: A total of 8034
patients who underwent pancreatic (n = 397), colorectal (n = 5808), or gastric (n
= 1829) resections were included in the study. In each resection group, the
majority of patients experienced hypophosphatemia postresection with the nadir on
postoperative day (POD) 2, and the subgroups that developed OSC exhibited lower
phosphate levels on POD3-7. On multivariate analysis, lower phosphate level on
POD3 remained significantly associated with OSC following pancreatic resection
[median (interquartile range) mmol/L, 0.65 (0.53-0.76) vs. 0.71 (0.61-0.84), p =
0.045] and colorectal resection [0.71 (0.61-0.87) vs. 0.77 (0.65-0.94), p =
0.006], and lower phosphate level on POD4 remained associated with OSC following
gastric resection [0.87 (0.74-1.03) vs. 0.96 (0.81-1.13), p = 0.049]. CONCLUSION:
This study identified a consistent trajectory of serum phosphate levels following
3 different gastrointestinal operations and association between early
postoperative phosphate levels and OSC. Persistent lower phosphate levels should
raise the level of concern for evolving postoperative leak and may lead to
earlier radiographic evaluation and treatment.
PMID- 29955939
TI - Fetal brain MRI in Apert syndrome: early in vivo detection of temporal lobe
malformation.
PMID- 29955940
TI - A comprehensive review of the clivus: anatomy, embryology, variants, pathology,
and surgical approaches.
AB - INTRODUCTION: The clivus is a bony structure formed by the fusion of the
basioccipital and basispheniod bone at the sphenooccipital synchondrosis. This
downward sloping structure from the dorsum sellae to the foramen magnum is
derived from mesoderm and ectoderm properties. METHODS: This comprehensive review
of the clivus will discuss its basic anatomy, embryology, pathological findings,
and surgical implications. The clivus is an endochondral bone, formed under two
processes; first, a cartilaginous base is developed, and it is secondly
reabsorbed and replaced with bone. Knowledge of its embryological structure and
growth of development will clarify the pathogenesis of anatomical variants and
pathological findings of the clivus. CONCLUSIONS: Understanding the anatomy
including proximity to anatomical structures, adjacent neurovasculature
properties, and anatomical variants will aid neurosurgeons in their surgical
management when treating pathological findings around the clivus.
PMID- 29955941
TI - Transcranial Doppler in pediatric emergency and intensive care unit: a case
series and literature review.
AB - PURPOSE: Transcranial Doppler (TCD) has been used for more than 30 years in
clinical practice. Although adult intensive care is relatively well covered,
pediatric cases are still underrepresented. We intend to review a series of
pediatric cases where TCD was determinant in clinical decisions and a literature
review on this topic. METHODS: We describe cases with different pathologies where
TCD had an important role in clinical management of the patients. We discuss TCD
utility and potential role both in the emergency department and the intensive
care unit. RESULTS: Five patients with different neurologic insults are
presented. TCD was useful in the identification of intracranial hypertension in
traumatic brain injury, hydrocephalus and central nervous system infection;
identification of decreased cerebral perfusion pressure in hypovolemic shock and
the diagnosis of impending cerebral circulatory arrest in a child with
meningococcal septicemia. We discuss how TCD can be used in emergency and
intensive care settings, reviewing relevant literature and our own experience.
CONCLUSIONS: Non-invasive testing using TCD can aid clinical decisions. More
widespread use of this technique will allow for better care of children with
neurologic insults.
PMID- 29955942
TI - Topical vancomycin for surgical prophylaxis in non-instrumented pediatric spinal
surgeries.
AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine if topical
vancomycin irrigation reduces the incidence of post-operative surgical site
infections following pediatric spinal procedures. Surgical site infections (SSIs)
following spinal procedures performed in pediatric patients represent a serious
complication. Prophylactic use of topical vancomycin prior to closure has been
shown to be effective in reducing incidence of SSIs in adult spinal procedures.
Non-instrumented cases make up the majority of spinal procedures in pediatric
patients, and the efficacy of prophylactic topical vancomycin in these procedures
has not previously been reported. METHODS: This retrospective study reviewed all
non-instrumented spinal procedures performed over a period from 05/2014-12/2016
for topical vancomycin use, surgical site infections, and clinical variables
associated with SSI. Topical vancomycin was utilized as infection prophylaxis,
and applied as a liquid solution within the wound prior to closure. RESULTS:
Ninety-five consecutive, non-instrumented, pediatric spinal surgeries were
completed between 01/2015 and 12/2016, of which the last 68 utilized topical
vancomycin. There was a 11.1% SSI rate in the non-topical vancomycin cohort
versus 0% in the topical vancomycin cohort (P = 0.005). The number needed to
treat was 9. There were no significant differences in risk factors for SSI
between cohorts. There were no complications associated topical vancomycin use.
CONCLUSIONS: Routine topical vancomycin administration during closure of non
instrumented spinal procedures can be a safe and effective tool for reducing SSIs
in the pediatric neurosurgical population.
PMID- 29955943
TI - Drug-to-drug interactions of tyrosine kinase inhibitors in chronic myeloid
leukemia patients. Is it a real problem?
AB - With tyrosine kinase inhibitors (TKI), chronic myeloid leukemia (CML) patients
are achieving similar rates of survival to the general population and some
treatment aspects such as adherence and drug-to-drug interactions (DDI) are
becoming increasingly important. Our aim was to investigate the frequency and
real clinical consequences of DDI between TKI and concurrent medications in CML.
We performed a retrospective multicenter study including 105 patients receiving
134 TKI treatments. Sixty-three patients (60%) had at least one potential DDI.
The mean number of concomitant medications was 4.8 (0-19). The mean number of DDI
by TKI treatment was 1.2 (0-8); it increased with the number of concomitant
medications and age in a significant manner. A total of 159 DDI were detected,
involving 55 different drugs. The most common drug classes involved were proton
pump inhibitors, statins, and antidepressants. A DDI-related clinical effect
(toxicity and/or lack of efficacy) was suspected during the common course of
patient follow-up in only five patients (4.7%). This number increased to 20% when
data were centrally reviewed. Most of the adverse events (AE) attributed to DDIs
were mild. The most common were diarrhea, vomiting, edema, cramps, and
transaminitis. Nilotinib and dasatinib showed a tendency towards a higher risk of
DDI compared with imatinib. There were no significant differences in AE frequency
or in treatment response between patients with or without DDI. Due to their
frequency, and their potential to cause clinically relevant effects, DDI are an
important aspect of CML management.
PMID- 29955944
TI - In contrast to high CD49d, low CXCR4 expression indicates the dependency of
chronic lymphocytic leukemia (CLL) cells on the microenvironment.
AB - CD49d and CXCR4 are key determinants of interactions between chronic lymphocytic
leukemia (CLL) tumor cells and their microenvironment. In this study, we
investigated the effect of CD49d and CXCR4 expressions on survival of CLL cells.
Primary CLL cells were cultured with CD49d ligand, VCAM-1, or bone marrow stromal
cells (BMSCs); then, apoptosis and immunophenotype analyses were performed. VCAM
1 treatment could not induce direct apoptosis protection or immunophenotype
change on the CD49d-expressing CLL cells, but resulted in actin reorganization.
The BMSC-induced apoptosis protection was independent from the presence of CD49d
expression of CLL cells, but showed an inverse correlation with their CXCR4
expression level. We suppose that CD49d contributes to enhanced survival of
leukemic cells by mediating migration to the protective microenvironment, not by
direct prevention of apoptosis. Moreover, CLL cells with low CXCR4 expression
represent a subpopulation that is more dependent on the microenvironmental
stimuli for survival, and show increased "death by neglect" when separated from
the supportive niche.
PMID- 29955945
TI - Association of gout with osteoporotic fractures.
AB - PURPOSE: Previous studies have shown that serum uric acid levels and inflammation
are associated with bone mineral density. Gout, a disease characterized by
hyperuricemia and inflammation, contributes to the risk of osteoporotic
fractures. However, this association is controversial. Therefore, this study
investigated whether gout in older people (age > 55 years) is associated with
osteoporotic fracture risk. METHODS: This population-based, cross-sectional study
included 2674 participants (147 cases of gout and 388 fractures). Standardized
and self-administered questionnaires were employed and physical examinations,
blood tests, and bone mineral density examinations were performed; multivariate
adjusted logistic regression models were used to evaluate associations between
gout and osteoporotic fracture risk. RESULTS: The data were adjusted for age;
smoking status; alcohol status; physical activity; body mass index; waist
circumference; hypertension; cardiovascular events; diabetes mellitus; rheumatoid
arthritis; serum levels of total cholesterol (TC), triglycerides, and high- and
low-density lipids; and T-scores. We found a significant association between gout
and osteoporotic fracture risk in women (odds ratio [OR], 2.00; 95% confidence
interval [CI], 1.12-3.56; P = 0.019), but no such association in men (OR, 1.30;
95% CI, 0.58-2.88; P = 0.525). Further stratified analyses showed a significant
association between gout and osteoporotic fracture risk in women without
rheumatic arthritis and in those with high TC levels or with osteoporosis (all, P
< 0.05). CONCLUSIONS: In older Chinese adults, gout is significantly associated
with the risk of osteoporotic fractures in women, especially those without
rheumatic arthritis and in those with high TC levels or with osteoporosis.
PMID- 29955946
TI - Functional outcomes after the Sauve-Kapandji procedure for distal radio-ulnar
post-traumatic instability: a case-control comparison of three different
operative methods of stabilization of the ulnar stump.
AB - PURPOSE: This study was performed to elucidate the cause of proximal ulnar stump
pain by comparing the clinical results and radiographic changes among three
treatment groups involving different Sauve-Kapandji procedures. METHODS: Thirty
seven patients (38 wrists) with distal radioulnar joint disorders followed up for
>= six months post-operatively were investigated. Patients were treated by one of
three Sauve-Kapandji procedures. In group A (13 wrists), the original Sauve
Kapandji procedure was performed. Groups B (13 wrists) and C (12 wrists) involved
different modified Sauve-Kapandji procedures with stabilization of the proximal
ulnar stump using the extensor carpi ulnaris tendon. At the final examination, we
evaluated wrist pain, proximal ulnar stump pain, the ranges of forearm
pronation/supination, grip strength, the grip strength ratio between the affected
and unaffected sides, and the clinical evaluation score. Standard posteroanterior
and lateral radiographs during rest and during maximal gripping were taken for
each patient at the final examination, and radiographic parameters were measured.
RESULTS: Although significant differences in the frequency of ulnar stump pain
were observed between group A and group B or C, no significant differences in
wrist pain or the clinical evaluation score were observed. Moreover, no
differences in the radiographic changes were noted among the three procedures.
CONCLUSION: These findings suggest that proximal ulnar stump pain may be caused
not by radial or dorsal deviation of the proximal ulnar stump but by other
dynamic factors.
PMID- 29955947
TI - Statistical analysis for obtaining optimum number of CT scanners in patient dose
surveys for determining national diagnostic reference levels.
AB - OBJECTIVES: To statistically determine an 'optimum number of CT scanners' for
obtaining 'diagnostic reference levels' (DRLs) in CT examinations as close as
possible to 'ideal DRLs' when all available CT scanners are considered. METHODS:
First, six 'ideal DRLs' (CTDIVol and DLP) were determined for head, chest and
abdomen/pelvis examinations by using patient-dose survey data of 100 CT scanners
of different models in Tehran. Then, a 'random sampling method' was applied to
different percent fractions of patient dose data of 100 CT scanners. The percent
differences (PD) of the DRLs obtained from 'ideal DRLs' and their coefficients of
variation (CVs) were calculated. The 'optimum number of CT scanners' determined
met those of 'ideal DRL' criteria; i.e. precision (CV <= 10%) and accuracy (PD <=
10%). RESULTS: 'Optimum number of CT scanners' for determining DRLs as close as
possible to 'ideal DRLs', fulfilling the stated criteria, is 43 instead of using
100. CONCLUSION: 'Optimum number of CT scanners' for obtaining DRLs as close as
possible to 'ideal DRLs' was determined. This optimum number can be effectively
applied in patient-dose survey situations with limited resources in a time- and
cost-effective manner. KEY POINTS: * Ideal DRLs were determined by a CT patient
dose survey applied to available scanners. * 'Optimum number of CT scanners'
statistically determined for DRLs is 43%. * Optimum number can be used for DRLs
as if 'ideal DRLs' were determined by all scanners.
PMID- 29955948
TI - Combined hepatocellular cholangiocarcinoma: LI-RADS v2017 categorisation for
differential diagnosis and prognostication on gadoxetic acid-enhanced MR imaging.
AB - OBJECTIVES: To investigate the performance of the Liver Imaging Reporting and
Data System (LI-RADS) v2017 for combined hepatocellular cholangiocarcinoma (cHCC
CCA) in the differential diagnosis from hepatocellular carcinoma (HCC) and
prediction of prognosis on gadoxetic acid-enhanced MRI (Gd-EOB-MRI). METHODS:
Patients at high risk of HCC with pathologically confirmed cHCC-CCAs (n = 70) and
a matched control of HCCs (n = 70) who had undergone Gd-EOB-MRI were included. LI
RADS category was assigned for each lesion by two radiologists. Imaging features
and surgical outcomes were compared between cHCC-CCAs of LR-M and LR-5/4 using
the chi2 test or Fisher's exact test. Recurrence-free survival (RFS) was
estimated using Kaplan-Meier survival curves and compared using the log-rank
test. RESULTS: cHCC-CCAs and HCCs were categorised as LR-M, LR-5/4 and LR-TIV in
61.4% (43/70), 37.1% (26/70) and 1.4% (1/70) and 10.0% (7/70), 88.6% (62/70) and
1.4% (1/70), respectively. cHCC-CCAs of LR-5/4, in comparison to LR-M, showed
significantly higher frequencies of major HCC features: arterial hyperenhancement
(96.2% (25/26) vs. 58.1% (25/43), p = 0.001), washout appearance (80.8% (21/26)
vs. 48.8% (21/43), p = 0.011) and enhancing capsule (34.6% (9/26) vs. 11.6%
(5/43), p = 0.031). After curative surgery, patients with cHCC-CCAs of LR-M
showed a higher early recurrence rate (<= 6 months) than did those with LR-5/4
(27.8% (10/36) vs. 4.8% (1/21), p = 0.041), whereas no significant difference was
observed in RFS (log-rank p = 0.084). CONCLUSIONS: By using LI-RADS on Gd-EOB
MRI, a substantial proportion of cHCC-CCAs can be categorised as non-LR-M. In
addition, cHCC-CCAs mimicking HCCs on imaging (LR-5/4) may indicate better
surgical outcomes with regard to early recurrence than those of LR-M. KEY POINTS:
* cHCC-CCAs can be categorised as either LR-M or non-LR-M on Gd-EOB-MRI. * cHCC
CCAs of LR-5/4 frequently demonstrate major HCC imaging features. * LI-RADS
categorisation may provide prognostic information after surgery in cHCC-CCAs.
PMID- 29955949
TI - Is the epicardial adipose tissue area on non-ECG gated low-dose chest CT useful
for predicting coronary atherosclerosis in an asymptomatic population considered
for lung cancer screening?
AB - OBJECTS: The purpose was to determine whether the epicardial adipose tissue (EAT)
area on low-dose chest CT (LDCT) could be used to predict coronary
atherosclerosis in an asymptomatic population considered for lung cancer
screening. METHODS: Subjects aged 55-80 years with smoking history who underwent
both LDCT and coronary CT angiography (CCTA) were retrospectively enrolled.
Correlation between the EAT volume in CCTA and EAT area in LDCT was evaluated.
Coronary risk factors including the body surface area (BSA) indexed EAT area were
compared between coronary plaque negative and positive groups. Significant
factors for predicting coronary atherosclerosis were analyzed with logistic
regression analysis. Receiver-operating characteristic curve analysis was
performed to determine the cutoff value. RESULTS: A total of 438 subjects were
enrolled, including 299 subjects with coronary atherosclerosis. There was a good
correlation between the EAT volume in CCTA and EAT area in LDCT (rho = 0.712, p <
0.001). There were significant differences in age, systolic blood pressure, all
BSA indexed EAT area, sex, and hypertension between plaque negative and positive
groups. In multivariate logistic regression for the BSA indexed EAT area in LDCT
at the RCA level, sex (OR: 11.168, 95% CI: 2.107-59.201, p = 0.005), systolic
blood pressure (OR: 1.021, 95% CI: 1.005-1.036, p = 0.009), hypertension (OR:
1.723, 95% CI: 1.103-2.753, p = 0.017), and EAT area (OR: 1.273, 95% CI: 1.154
1.405, p < 0.001) were significant. The area under the curve of the BSA indexed
EAT area in LDCT at the RCA level for coronary atherosclerosis was 0.657, and the
cut-off value was 7.66 cm2/m2. CONCLUSION: The EAT area in LDCT could be used to
predict coronary atherosclerosis in an asymptomatic population considered for
lung cancer screening. KEY POINTS: * To quantify EAT, the EAT area in LDCT can be
used instead of the EAT volume in CCTA. * The EAT area measured in LDCT can be
used as a predictor of coronary artery disease. * The extensive CAD group tended
to have a greater EAT area than the non-extensive CAD group.
PMID- 29955950
TI - The insulin receptor is differentially expressed in somatic and visceral primary
sensory neurons.
AB - Recent studies demonstrated the expression of the insulin receptor (InsR) and its
functional interaction with the transient receptor potential vanilloid type 1
receptor (TRPV1) in primary sensory neurons (PSNs). The present study was
undertaken to reveal the target-specific expression of the InsR and its co
localization with the TRPV1 in rat PSNs. We assessed the localization of the InsR
and its co-localization with the TRPV1 in PSNs retrogradely labelled with biotin
conjugated wheat germ agglutinin injected into the dorsal hind paw skin, the
gastrocnemius muscle, the pancreas and the urinary bladder wall. The largest
proportions of retrogradely labelled InsR-immunoreactive neurons were identified
among PSNs serving the pancreas (~ 54%) and the urinary bladder (~ 53%). The
proportions of retrogradely labelled InsR-immunoreactive neurons innervating the
dorsal hind paw skin and the gastrocnemius muscle amounted to ~ 22 and ~ 21%.
TRPV1-immunoreactive neurons amounted to ~ 63, ~ 62, ~ 67 and ~ 65% of
retrogradely labelled cutaneous, muscle, pancreatic and urinary bladder PSNs,
respectively. Co-localization of the TRPV1 with the InsR was observed in ~ 16, ~
15, ~ 29 and ~ 30% of retrogradely labelled cutaneous, muscle, pancreatic and
urinary bladder PSNs. These quantitative immunohistochemical data demonstrate a
preponderance of InsR-immunoreactivity among PSNs, which innervate visceral
targets. The present findings suggest that visceral spinal PSNs are more likely
to be exposed to the modulatory effects of insulin on sensory functions,
including neurotrophic, nociceptive and inflammatory processes.
PMID- 29955951
TI - Mesenchymal stromal cell-derived extracellular vesicles: regenerative and
immunomodulatory effects and potential applications in sepsis.
AB - Mesenchymal stromal (stem) cells (MSCs) have multipotent differentiation capacity
and exist in nearly all forms of post-natal organs and tissues. The
immunosuppressive and anti-inflammatory properties of MSCs have made them an
ideal candidate in the treatment of diseases, such as sepsis, in which
inflammation plays a critical role. One of the key mechanisms of MSCs appears to
derive from their paracrine activity. Recent studies have demonstrated that MSC
derived extracellular vesicles (MSC-EVs) are at least partially responsible for
the paracrine effect. MSC-EVs transfer molecules (such as proteins/peptides,
mRNA, microRNA and lipids) with immunoregulatory properties to recipient cells.
MSC-EVs have been shown to mimic MSCs in alleviating sepsis and may serve as an
alternative to whole cell therapy. Compared with MSCs, MSC-EVs may offer specific
advantages due to lower immunogenicity and higher safety profile. The first two
sections of the review discuss the preclinical and clinical findings of MSCs in
sepsis. Next, we review the characteristics of EVs and MSC-EVs. Then, we
summarize the mechanisms of MSC-EVs, including tissue regeneration and
immunomodulation. Finally, our review presents the evidences that MSC-EVs are
effective in treating models of sepsis. In conclusion, MSC-EVs may have the
potential to become a novel therapeutic strategy for sepsis.
PMID- 29955952
TI - Efficacy of GnRH agonist trigger in women having history of follicular
endometrial asynchrony with clomiphene/IUI cycles in unexplained infertility.
AB - PURPOSE: An alternative option to human chorionic gonadotropin (hCG) is GnRH
agonist (GnRH-a) for ovulation trigger in intrauterine insemination (IUI) cycles.
This study aims to compare the efficacy of GnRH-a with hCG in women with history
of follicular-endometrial asynchrony after clomiphene in IUI cycles. METHODS:
This prospective observational study recruited 631 women with unexplained
infertility and follicular-endometrial asynchrony (follicle >= 18 mm, endometrial
thickness (ET) < 7 mm) in previous two failed clomiphene/IUI cycles. Overall 27
patients with synchronized follicular-endometrial relationship and 49 women with
persistent ET < 7 mm and/or follicle > 26 mm were excluded. Remaining women (n =
555) were divided into two groups: Group A (n = 285) received GnRH-a and Group B
(n = 270) received hCG ovulation trigger. Finally, 513 patients, who underwent
IUI, were analysed. RESULTS: Cancellation due to luteinized unruptured follicle
was more in hCG group (P = 0.01). Higher clinical pregnancies (10.33 vs. 4.96%, P
= 0.03) and live birth rates (8.86 vs. 4.13%, P = 0.03) were noted with GnRH-a
trigger. Miscarriage rate was comparable in both the groups (10.71 and 16.67% in
Group A and Group B, respectively). CONCLUSION: In unexplained infertility, GnRH
agonist is an useful alternative for triggering ovulation in women with
follicular-endometrial asynchrony following clomiphene induction.
PMID- 29955953
TI - Tongue Shape Dynamics in Swallowing Using Sagittal Ultrasound.
AB - Ultrasound imaging is simple, repeatable, gives real-time feedback, and its
dynamic soft tissue imaging may make it superior to other modalities for
swallowing research. We tested this hypothesis and measured certain spatial and
dynamic aspects of the swallowing to investigate its efficacy. Eleven healthy
adults wearing a headset to stabilize the probe participated in the study. Both
thickened and thin liquids were used, and liquid bolus volumes of 10 and 25 ml
were administered to the subjects by using a cup. The tongue's surface was traced
as a spline superimposed on a fan-shaped measurement space for every image from
the time at which the tongue blade started moving up toward the palate at the
start of swallowing to the time when the entire tongue was in contact with the
palate. To measure depression depth, the distance (in mm) was measured along each
radial fan line from the location at which the tongue's surface spline
intersected the fan line to the point where the hard palate intersected the fan
line at each timepoint. There were differences between individual participants in
the imageability of the swallow, and so we defined quantitatively "measureable"
and "unmeasurable" types. The most common type was measureable, in which we could
find a clear bolus depression in the cupped tongue's surface. Indeed, with 10 ml
of thin liquids, we were able to find and measure the depression depth for all
participants. The average maximum radial distance from the palate to the tongue's
surface was 20.9 mm (median) (IQR: 4.3 mm) for swallowing 10 ml of thin liquid
compared to 24.6 mm (IQR: 3.3 mm) for 25 ml of thin liquid swallow (p < 0.001).
We conclude that it is possible to use ultrasound imaging of the tongue to
capture spatial aspects of swallowing.
PMID- 29955954
TI - Egg white hydrolysate and peptide reverse insulin resistance associated with
tumor necrosis factor-alpha (TNF-alpha) stimulated mitogen-activated protein
kinase (MAPK) pathway in skeletal muscle cells.
AB - PURPOSE: Excessive formation of tumor necrosis factor-alpha (TNF-alpha), a pro
inflammatory cytokine, has been implicated in the development of insulin
resistance in obesity and type-2 diabetes. In skeletal muscle, chronic exposure
to TNF-alpha impairs insulin-stimulated glucose uptake and insulin signaling. The
aim of this study is to investigate the effects of enzymatic egg white
hydrolysate (EWH) and its responsible peptide, IRW, on TNF-alpha-induced insulin
resistance and the underlying molecular mechanisms using rat skeletal muscle
cells (L6 cells). METHODS: Insulin resistance was induced by treating L6 cells
with 5 ng/ml TNF-alpha for 24 h. Effects of EWH and IRW on glucose uptake were
detected by glucose uptake assay, glucose transporter 4 (GLUT4) translocation by
immunofluorescence, and western blot, while insulin-signaling pathway and mitogen
activated protein kinase (MAPK) pathway were investigated using western blot.
RESULTS: Adding both EWH and IRW significantly improved glucose uptake in TNF
alpha-treated cells, increased activation of insulin receptor substrate (IRS-1)
tyrosine residue and protein kinase B (Akt), whereas decreased activation of IRS
1 serine residue. In addition, TNF-alpha-induced activation of p38-mitogen
activated protein kinase (p38) and c-Jun N-terminal kinases (JNK) 1/2 were
decreased by either EWH or IRW treatment. CONCLUSION: EWH and IRW improve
impaired insulin sensitivity by down-regulating the activation of p38 and JNK1/2
in TNF-alpha-treated skeletal muscle cells.
PMID- 29955955
TI - [Lupus nephritis].
AB - Lupus nephritis (LN) is a common major organ manifestation of systemic lupus
erythematosus (SLE) and causes significantly increased morbidity and mortality.
Thus, all patients with SLE should be regularly screened for LN. While new onset
glomerular hematuria or proteinuria are suggestive for LN, a kidney biopsy is the
gold standard for diagnosis and classification. The treatment of LN comprises
strict blood pressure control and administration of hydroxychloroquine.
Aggressive forms of LN require additional treatment with immunosuppressive
induction therapy followed by a maintenance phase for several years. Given the
high rate of disease recurrence, life-long follow-up control in specialized
centers is necessary. Despite optimal care a significant proportion of patients
still develop chronic kidney failure. Better disease activity markers as well as
more potent and specific therapeutic agents are thus urgently needed.
PMID- 29955956
TI - Rechallenge with oxaliplatin and peripheral neuropathy in colorectal cancer
patients.
AB - BACKGROUND: Oxaliplatin (OXA) is a cornerstone in the treatment of colorectal
cancer (CRC). Retreatment with OXA is frequently considered as salvage treatment.
OXA-induced neuropathy (OIN) is the most frequent and feared long-term side
effect. PATIENTS AND METHODS: CRC patients receiving at least twice OXA-based
chemotherapy lines at our institution between June 2000 and July 2016 were
reviewed. The aim of this study was to investigate whether retreatment with OXA
increases the risk of developing new or worsening previous neuropathy. OIN was
assessed by National Cancer Institute-Common Toxicity Criteria for Adverse Events
(NCI), Total Neuropathy Score(c) (TNS) and nerve-conduction studies. RESULTS: 106
patients were included in the analysis. Median age at OXA-based retreatment was
61.5 (20-83) years. After the first OXA-based chemotherapy treatment, 63.4% of
patients developed OIN, 30.7 and 8.9% grades 2 and 3, respectively, after a
median of 11 (1-17) cycles. After 30 (11-90) months of median to retreatment with
a median of 8 (1-14) OXA cycles, 39.6, 22.6, and 0% of patients developed grade
1, 2, and 3 OIN, respectively. Worsening of the previous OIN was observed in one
third (31.1%) of all patients. OXA-cumulative dose was independently associated
with greater risk of worsening OIN (p < 0.001). Non-significant trend towards
higher TNSc(c) scores after retreatment was observed [5 (0-11) vs 6 (3-13), p =
0.083]. CONCLUSION: Retreatment with OXA in CRC patients is a feasible option
even in patients who previously developed moderate or severe OIN. One-third of
patients' OIN was worsened by retreatment. Neurological monitoring should be
considered.
PMID- 29955958
TI - Tapping ahead of time: its association with timing variability.
AB - Researchers have puzzled over the phenomenon in sensorimotor timing that people
tend to tap ahead of time. When synchronizing movements (e.g., finger taps) with
an external sequence (e.g., a metronome), humans typically tap tens of
milliseconds before event onsets, producing the elusive negative asynchrony.
Here, we present 24 metronome-tapping data sets from 8 experiments with different
experimental settings, showing that less negative asynchrony is associated with
lower tapping variability. Further analyses reveal that this negative mean-SD
correlation of asynchrony is likely to be observed for sequence types appropriate
for synchronization, as indicated by the statistically negative lag 1
autocorrelation of inter-response intervals. The reported findings indicate an
association between negative asynchrony and timing variability.
PMID- 29955957
TI - De novo variants in GREB1L are associated with non-syndromic inner ear
malformations and deafness.
AB - Congenital inner ear malformations affecting both the osseous and membranous
labyrinth can have a devastating impact on hearing and language development. With
the exception of an enlarged vestibular aqueduct, non-syndromic inner ear
malformations are rare, and their underlying molecular biology has thus far
remained understudied. To identify molecular factors that might be important in
the developing inner ear, we adopted a family-based trio exome sequencing
approach in young unrelated subjects with severe inner ear malformations. We
identified two previously unreported de novo loss-of-function variants in GREB1L
[c.4368G>T;p.(Glu1410fs) and c.982C>T;p.(Arg328*)] in two affected subjects with
absent cochleae and eighth cranial nerve malformations. The cochlear aplasia in
these affected subjects suggests that a developmental arrest or problem at a very
early stage of inner ear development exists, e.g., during the otic pit formation.
Craniofacial Greb1l RNA expression peaks in mice during this time frame (E8.5).
It also peaks in the developing inner ear during E13-E16, after which it
decreases in adulthood. The crucial function of Greb1l in craniofacial
development is also evidenced in knockout mice, which develop severe craniofacial
abnormalities. In addition, we show that Greb1l-/- zebrafish exhibit a loss of
abnormal sensory epithelia innervation. An important role for Greb1l in sensory
epithelia innervation development is supported by the eighth cranial nerve
deficiencies seen in both affected subjects. In conclusion, we demonstrate that
GREB1L is a key player in early inner ear and eighth cranial nerve development.
Abnormalities in cochleovestibular anatomy can provide challenges for cochlear
implantation. Combining a molecular diagnosis with imaging techniques might aid
the development of individually tailored therapeutic interventions in the future.
PMID- 29955959
TI - Optimizing SGLT inhibitor treatment for diabetes with chronic kidney diseases.
AB - Diabetes induces glomerular hyperfiltration, affects kidney function, and may
lead to chronic kidney diseases. A novel therapeutic treatment for diabetic
patients targets the sodium-glucose cotransporter isoform 2 (SGLT2) in the
kidney. SGLT2 inhibitors enhance urinary glucose, [Formula: see text] and fluid
excretion and lower hyperglycemia in diabetes by inhibiting [Formula: see text]
and glucose reabsorption along the proximal convoluted tubule. A goal of this
study is to predict the effects of SGLT2 inhibitors in diabetic patients with and
without chronic kidney diseases. To that end, we applied computational rat kidney
models to assess how SGLT2 inhibition affects renal solute transport and
metabolism when nephron population are normal or reduced (the latter simulates
chronic kidney disease). The model predicts that SGLT2 inhibition induces
glucosuria and natriuresis, with those effects enhanced in a remnant kidney. The
model also predicts that the [Formula: see text] transport load and thus oxygen
consumption of the S3 segment are increased under SGLT2 inhibition, a consequence
that may increase the risk of hypoxia for that segment. To protect the vulnerable
S3 segment, we explore dual SGLT2/SGLT1 inhibition and seek to determine the
optimal combination that would yield sufficient urinary glucose excretion while
limiting the metabolic load on the S3 segment. The model predicts that the
optimal combination of SGLT2/SGLT1 inhibition lowers the oxygen requirements of
key tubular segments, but decreases urine flow and [Formula: see text] excretion;
the latter effect may limit the cardiovascular protection of the treatment.
PMID- 29955960
TI - Combined mechanisms of neural firing rate homeostasis.
AB - Spikes in the membrane potential of neurons comprise the currency of information
processing in the brain. The ability of neurons to convert any information
present across their multiple inputs into a significant modification to the
pattern of their emitted spikes depends on the rate at which they emit spikes. If
the mean rate is near the neuron's maximum, or if the rate is near zero, then
changes in the inputs have minimal impact on the neuron's firing rate. Therefore,
a neuron needs to control its mean rate. Protocols that either dramatically
increase or decrease a neuron's firing rate lead to multiple compensatory changes
that return the neuron's mean rate toward its prior value. In this primer, first
as a summary of our previous work (Cannon and Miller in J Neurophysiol
116(5):2004-2022, 2016; Cannon and Miller in J Math Neurosci 7(1):1, 2017), we
describe the advantages and disadvantages of having more than one such control
mechanism responding to the neuron's firing rate. We suggest how problems of two,
coexisting, potentially competing mechanisms can be overcome. Key requirements
are: (1) the control be of a distribution of values, which the controlled
variable achieves over a fast timescale compared to the timescale of the control
system; (2) at least one of the control mechanisms be nonlinear; and (3) the two
control systems are satisfied by a stable distribution or range of values that
can be achieved by the variable. We show examples of functional control systems,
including the previously studied integral feedback controller and new simulations
of a "bang-bang" controller, that allow for compensation when inputs to the
system change. Finally, we present new results describing how the underlying
signal processing pathways would produce mechanisms of dual control, as opposed
to a single mechanism with two outputs, and compare the responses of these
systems to changes of input statistics.
PMID- 29955961
TI - A case series of patients change in mobility following a hip fracture.
AB - INTRODUCTION: Hip fractures are common in the elderly population. It is currently
believed that patients can expect to lose a level of mobility following a hip
fracture. The aim of this study was to compare the pre- and post-treatment
mobility of patients treated in our institution who had suffered a fracture neck
of femur and identify the factors that could predict pre-operatively those
patients who would suffer a deterioration in mobility after treatment. METHODS:
Patients admitted to a large UK teaching hospital with a surgically treated neck
of femur fracture were included between 2 April 2011 and 31 March 2014. Patient's
mobility was assessed on admission and at 1 year following surgery. RESULTS:
There were a total of 615 patients alive at 1 year. There were 142 males and 473
females with a mean age of 82.1 (range 47-100). On admission, 338 (55.0%)
mobilised independently 52.2% had no change in their pre-fracture mobility at 1
year following their treatment. Age, a lower AMTS, a higher ASA and living in
residential care were significant risk factors for not regaining their pre
fracture mobility. Sex and type of fracture were not associated with change in
mobility. CONCLUSION: It is commonly stated that patients lose one level of
mobility following a hip fracture. This case series demonstrates that over 50% of
patients can expect to have the same level of mobility at 1 year post-surgery as
they did previously.
PMID- 29955962
TI - Surgical technique: about a new total and isoelastic wrist implant
(Prosthelast(r)).
AB - This study describes a new total wrist implant (Prosthelast(r)) designed to
reduce the risk of distal migration of the carpal component. The Prosthelast(r)
implant consists in a one-block radial implant replacing the metaphysis and the
articular surface fixed to a radial elastic centromedullar wire and a carpal
component in titanium with an articular condylar surface in polyethylene. We
operated on five patients (three male patients and two female patients) and
followed them up for 12 months on average. Two of the patients presented with
rheumatoid arthritis of the wrist, and an ulnar osteotomy (Darrach procedure) was
carried out at the same time of the arthroplasty. All clinical variables improved
postoperatively (Quick DASH score, pain score, range of motion) except from wrist
flexion which was reduced. No patients underwent revision surgery. Two patients
presented with a periprosthetic radiolucent loosening around the radial
component, but no implant migration was observed. Overall, the preliminary
results of our case series show that the new Prosthelast(r) implant presents
comparable short-term results to those described in the literature. We will
follow up the patients to verify that long-term results are as satisfactory as
the short-term results.
PMID- 29955964
TI - Sandwich electrochemical thrombin assay using a glassy carbon electrode modified
with nitrogen- and sulfur-doped graphene oxide and gold nanoparticles.
AB - Graphene oxide doped with nitrogen and sulfur was decorated with gold
nanoparticles (AuNP-SN-GO) and applied as a substrate to modify a glassy carbon
electrode (GCE). An aptamer against the model protein thrombin was self-assembled
on the modified GCE which then was exposed to thrombin. Following aptamer
thrombin interaction, biotin-labeled DNA and aptamer 2 are immobilized on another
AuNP-SN-GO hybrid and then are reacted with the thrombin/AuNP-SN-GO/GCE to form a
sandwich. The enzyme label horseradish peroxidase (HRP) was then attached to the
electrode by biotin-avidin interaction. HRP catalyzes the oxidation of
hydroquinone by hydrogen peroxide. This generates a strong electrochemical signal
that increases linearly with the logarithm of thrombin concentration in the range
from 1.0 * 10-13 M to 1.0 * 10-8 M with a detection limit of 2.5 * 10-14 M (S/N =
3). The assay is highly selective. It provides a promising strategy for signal
amplification. In our perception, it has a large potential for sensitive and
selective detection of analytes for which appropriate aptamers are available.
Graphic abstract A sandwich-type electrochemical aptasensor is fabricated for
detection of thrombin using a glassy carbon electrode modified with nitrogen- and
sulfur-doped graphene oxide and gold nanoparticles.
PMID- 29955963
TI - Biomechanical approach for the assessment of contacts with deformable objects.
AB - Forensic and biomechanical assessment in case of blunt force trauma can be a
challenging task especially when deformable striking objects are used.
Evaluations solely based on empirical knowledge can lead to misjudgments. Semi
quantitative and quantitative investigations give the forensic assessment a
scientific basis comprising experimental and calculation methods. Based on a real
case where a car wheel was used as a striking object, our work presents a simple
test setup for contact force estimation in head contacts with deformable contact
partners. Our approach combines experimental measurements using a single
accelerometer and calculations applying the conservation of linear momentum and
Newton's second law. Both experimental and calculation results are discussed in
terms of validity, reproducibility, and plausibility. With regard to our case, we
can conclude that the injury pattern without skull fractures does not confound
multiple strikes with a wheel. Skull fractures and potential fatal injuries had
not to be expected assuming a head-carcass contact in case of a non-supported
head. The approach presented can be applied to any case where deformable or
uncommon blunt objects are used.
PMID- 29955965
TI - Immunoreactivity patterns of tight junction proteins are useful for differential
diagnosis of human salivary gland tumors.
AB - The expression pattern of tight junction proteins (TJPs) varies among organs and
tumor types. In this study, we examined the immunoreactivity of claudin (CLDN)-1,
-4, and -7, and JAM-A in salivary gland tumors (SGTs) by histological types and
cell types to estimate their usefulness as differential diagnostic markers.
Immunoreactivity of CLDN1 was higher in ductal epithelium cells of SGTs than in
non-tumor tissues. Conversely, immunoreactivity of CLDN1 was significantly
decreased in basal/myoepithelium cells of SGTs compared with that in non-tumor
tissues. There was no significant difference between the immunoreactivity of
CLDN1 in benign tumors and that in malignant tumors. Immunoreactivity of CLDN4,
CLDN7, and JAM-A in ductal epithelium cells was higher in many SGTs than in non
tumor tissues. There was a difference depending on the histological type of SGT
in immunoreactivity of CLDN4, CLDN7, and JAM-A in basaloid/myoepithelial cells.
It was possible to classify SGTs by a hierarchical clustering using
immunoreactivity of TJPs. The results suggest that an immunohistochemical marker
panel including these TJPs may be useful for differential diagnosis of SGTs and
that CLDN1 is associated with tumorigenesis of SGTs.
PMID- 29955966
TI - Comparative differentiation analysis of distinct oral tissue-derived cells in
response to osteogenic stimulation.
AB - BACKGROUND: Mixed cell populations from oral tissues may be superior to pure stem
cells for regenerative approaches. Therefore, the aim of the present study was to
explore the osteogenic potential of mixed cells derived from oral connective
tissues compared to alveolar osteoblasts. MATERIALS AND METHODS: Primary cells
were isolated from the alveolar bone, periodontal ligament and gingiva. Following
characterization by colony formation, growth capacity and flow cytometry, all
cells were subjected to osteogenic differentiation induction and screened for a
large panel of osteogenic markers using western blots, qPCR arrays, and matrix
mineralization and alkaline phosphatase quantification. RESULTS: Non-induced
mixed cells from gingiva showed higher colony formation efficiency but decreased
proliferation compared to non-induced periodontal mixed cells, while both
entities revealed similar surface markers tested in this setup. Following
osteogenic induction, all cell populations individually expressed receptors with
distinctively activated downstream effectors. Gene expression of induced
periodontal mixed cells was similar to alveolar osteoblasts, but was differently
modulated in gingival mixed cells. The latter failed to achieve osteogenic
differentiation in terms of matrix mineralization and alkaline phosphatase
activity, which was well observed in periodontal mixed cells and osteoblasts.
CONCLUSION: Mixed cells from periodontal ligament but not from gingiva feature an
inherent osteogenic capacity in vitro. From these results, it can be concluded
that periodontal cells do not require further stem cell enrichment in order to
qualify for bone regeneration. CLINICAL RELEVANCE: Our data contribute to the
development of novel cell-based therapies using mixed cells from the periodontal
ligament in regenerative periodontics.
PMID- 29955967
TI - Preconcentration of Pb(II) by using Mg(II)-doped NiFe2O4 nanoparticles as a
magnetic solid phase extraction agent.
AB - Magnesium(II)-doped nickel ferrite (Mg-NiFe2O4) nanoparticles are introduced as a
new adsorbent for magnetic solid phase extraction of lead(II) ions from aqueous
solutions. The structure and morphology of the adsorbent was characterized by
FTIR, X-ray diffraction and scanning electron microscopy. The effects of pH
value, amount of adsorbent, type, concentration and volume of the eluent and
adsorption/desorption time on the extraction efficiency were studied. Following
elution with hydrochloric acid, Pb(II) ions were quantified by flame atomic
absorption spectrometry. Under optimized conditions, the calibration graph is
linear in the 0.5-125 ng mL-1 Pb(II) ion concentration range. Other figures of
merit include (a) a 0.2 ng mL-1 limit of detection, (b) an enrichment factor of
200, (c) an intra-day relative standard deviation (for n = 6 at 50 ng mL-1) of
1.6%, and (d) an inter-day precision of 3.8%. The method was validated by the
analysis of the certified reference material, NIST SRM 1566b. It was successfully
applied to the determination of Pb(II) ion in spiked water samples, industrial
wastewater and acidic lead battery waters. Graphical abstract Schematic of the
synthesis of Mg(II)-doped NiFeO4 nanoparticles and their application as a
magnetic sorbent for solid-phase extraction of a Pb(II) ions prior to
determination by flame atomic absorption spectrometry (FAAS).
PMID- 29955968
TI - SPECT/CT-guided lymph drainage mapping for the planning of unilateral elective
nodal irradiation in head and neck squamous cell carcinoma.
AB - PURPOSE: To investigate the feasibility of lymph drainage mapping (LDM) using
SPECT/CT to help select head and neck cancer (HNSCC) patients for unilateral
elective neck irradiation (ENI). Patients with lateralized HNSCC treated with
radiotherapy routinely undergo bilateral ENI, despite the incidence of
contralateral regional failure being relatively low even after unilateral ENI. We
hypothesized that patients with a lateralized tumor without visible lymph
drainage to the contralateral neck have an extremely low risk of contralateral
involved nodes. Excluding the contralateral neck from elective irradiation will
reduce radiation-induced toxicity and improve quality-of-life. METHODS: Fifty
five patients with lateralized cT1-3N0-2bM0 HNSCC not crossing the midline
underwent LDM. Radiolabeled 99mTc-nanocolloid was injected in 4-5 depots around
and in the primary tumor. Lymph drainage patterns were visualized using planar
scintigraphy and SPECT/CT after 4 h. We report on the incidence of contralateral
drainage, the location of draining areas, and the size of underlying nodes.
RESULTS: Lymphatic drainage was successfully visualized in 54 patients (98%). In
11 patients (20%) with visible contralateral drainage, 14 draining areas (16
nodes; median volume 0.50 cc, diameter 8.0 mm) were identified. Neck levels with
contralateral drainage were level II (88%), III (25%), and IV (13%).
Contralateral drainage was significantly higher in T3 compared to T1-2 tumors (45
and 14%, respectively, P = 0.035). CONCLUSION: SPECT/CT-guided LDM is feasible
and can be used to guide unilateral ENI in HNSCC patients in prospective studies.
In addition, the anatomical confidence in visualization of contralateral drainage
indicates a potential for ENI limited to draining levels alone.
PMID- 29955970
TI - Risk of neurological injury in posterior bone block surgery for recurrent
glenohumeral instability: a cadaveric study.
AB - INTRODUCTION: Recurrent posterior glenohumeral instability poses a challenge for
treatment. Bone block procedures have been advocated in cases where a bony defect
is present. However, these techniques are not free of complications due to the
proximity of neurovascular structures. The aim of this study is to measure the
distance to the axillary and suprascapular nerves at the different steps of the
procedure. MATERIALS AND METHODS: Ten frozen human cadavers were used. The bone
graft was prepared and placed on the posterior aspect of the glenoid, where it
was fixed with two K-wires in different positions: parallel to the articular
surface and with 20 degrees of medial angulation. The distance from the entry
and exit points of the K-wires to the axillary and suprascapular nerves was
measured. RESULTS: At the exit point, mean distance from the superior K-wire to
the axillary nerve was 4.4 mm in the neutral position and 14.4 mm when medially
angulated (p = 0.01) and 2.6 mm and 11.5 mm, respectively, for the inferior K
wire (p < 0.01). No differences were found at the entry point (p = 0.7 and p =
0.3). For the suprascapular nerve, mean distance to the entry point of the
superior K-wire was significantly greater when it was inserted with 20 degrees
of medial angulation than when placed in neutral position (p = 0.04). No
differences were found for the inferior K-wire (p = 0.35). CONCLUSION: Posterior
bone block surgery should be performed taking into consideration the possibility
of axillary nerve injury anteriorly at the exit point of the K-wires. Wire and
screw insertion parallel to the glenoid articular surface may reduce the risk,
while increased wire or screw medial angulation with respect to the glenoid
surface may heighten risk. LEVEL OF EVIDENCE: Not applicable (cadaveric study).
PMID- 29955969
TI - Physeal bar resection using a patient-specific guide with intramedullary
endoscopic assistance for partial physeal arrest of the distal radius.
AB - The partial physeal arrest of the distal radius could result in progressive
deformities and functional problems of the wrist. Despite being the most
preferred surgical intervention, physeal bar resection (Langenskiold procedure)
is technically demanding. This manuscript aims to illustrate the technical tricks
and present an illustrative case of premature physeal arrest of the distal radius
managed with a novel method for the Langenskiold procedure, involving complete
removal of the bar using a patient-specific guide in combination with an
intramedullary endoscopy technique that facilitated direct observation.
PMID- 29955971
TI - Leishmanicidal activity of alpha-bisabolol from Tunisian chamomile essential oil.
AB - According to the World Health Organization, leishmaniasis is considered as a
major neglected tropical disease causing an enormous impact on global public
health. Available treatments were complicated due to the high resistance,
toxicity, and high cost. Therefore, the search for novel sources of anti
leishmania agents is an urgent need. In the present study, an in vitro evaluation
of the leishmanicidal activity of the essential oil of Tunisian chamomile
(Matricaria recutita L.) was carried out. Chamomile essential oil exhibits a good
activity on promastigotes forms of L. amazonensis and L. infantum with a low
inhibitory concentration at 50% (IC50) (10.8 +/- 1.4 and 10.4 +/- 0.6 MUg/mL,
respectively). Bio-guided fractionation was developed and led to the
identification of (-)-alpha-bisabolol as the most active molecule with low IC50
(16.0 +/- 1.2 and 9.5 +/- 0.1 MUg/mL for L. amazonensis and L. infantum,
respectively). This isolated sesquiterpene alcohol was studied for its activity
on amastigotes forms (IC50 = 5.9 +/- 1.2 and 4.8 +/- 1.3 MUg/mL, respectively)
and its cytotoxicity (selectivity indexes (SI) were 5.4 and 6.6, respectively).
The obtained results showed that (-)-alpha-bisabolol was able to activate a
programmed cell death process in the promastigote stage of the parasite. It
causes phosphatidylserine externalization and membrane damage. Moreover, it
decreases the mitochondrial membrane potential and total ATP levels. These
results highlight the potential use of (-)-alpha-bisabolol against both L.
amazonensis and L. infantum, and further studies should be undertaken to
establish it as novel leishmanicidal therapeutic agents.
PMID- 29955972
TI - Comparison of the horizontal diameter to a modeled area of traction in eyes with
vitreomacular traction: is the diameter close enough to the truth?
AB - PURPOSE: In daily practice, vitreomacular traction (VMT) is described by the
horizontal diameter of its attachment site implying a regular round shape of VMT.
We investigated the deviation from this circular area of vitreous traction in
patients with VMT. METHODS: A retrospective analysis of optical coherence
tomography (OCT) scans was performed. The area of vitreomacular attachment was
determined using six radial OCT scans (Ameasured). The assumed circular area of
traction was calculated based on measuring the maximal horizontal diameter for
comparison (Acircular). RESULTS: Thirty-seven eyes of 37 patients with pure VMT
were included. Patients' mean age was 72.8 +/- 8.2 years. Mean horizontal VMT
diameter was 400.8 +/- 230.5 MUm (median 361 MUm; range 44-991 MUm). While there
was no difference between mean areas of traction for Acircular and Ameasured (P =
0.93), the individual difference (|Acircular - Ameasured|) was 0.042 (+/- 0.044)
mm2 in mean or relative 73.0% (+/- 135.8%). A difference of >= 30% of Ameasured
to Acircular was found in 16 eyes (43.2%) and >= 100% in 7 eyes (18.9%),
respectively. CONCLUSION: Vitreous attachment sites possess an irregular non
circular shape in a significant number of eyes with VMT. Consequently, the area
of traction appears inaccurately described by its horizontal VMT diameter alone.
As the area of traction is important for therapeutic recommendation, our results
emphasize the need for a more precise description of the area of traction in eyes
with VMT.
PMID- 29955973
TI - Regional alterations of cerebral [18F]FDG metabolism in the chronic unpredictable
mild stress- and the repeated corticosterone depression model in rats.
AB - Preclinical research has been indispensable in the exploration of the
neurological basis of major depressive disorder (MDD). The present study aimed to
examine effects on regional brain activity of two frequently used depression
models, the chronic unpredictable mild stress (CUMS)- and the chronic
corticosterone (CORT) depression model. The CUMS and CORT depression model were
induced by exposing male Long-Evans rats to a 4-week procedure of unpredictable
mild stressors or a 3-week procedure of chronic corticosterone, respectively.
Positron emission tomography with [18F]FDG was performed to determine alterations
in regional brain activity. In addition, depressive- and anxiety-like behaviour
was assessed via the forced swim test and the open field test, respectively. The
chronic CORT administration, but not the CUMS model, significantly induced
depressive-like behaviour and elevated plasma corticosterone levels. Compared to
control, induction of the CORT depression model resulted in a significantly
reduced glucose consumption in the insular cortex and the striatum, and a
significantly elevated consumption in the cerebellum and the midbrain. Induction
of the CUMS model replicated the findings with respect to the activity in the
striatum region, and cerebellum, but missed significance in the insular cortex
and the midbrain. Based on the alterations in behaviour and regional [18F]FDG
uptake, a superior face validity and construct validity can be observed after
induction of depression via chronic CORT injections, compared to the used CUMS
paradigm.
PMID- 29955974
TI - Development of Breast Cancer Choices: a decision support tool for young women
with breast cancer deciding whether to have genetic testing for BRCA1/2
mutations.
AB - PURPOSE: To develop a decision support tool for young women with breast cancer
considering genetic testing for BRCA1/2 mutations soon after cancer diagnosis.
METHODS: A four-stage iterative development process was employed; stage 1,
literature review exploring the availability and efficacy of empirically tested
decision support tools; stage 2, in-depth interviews with 29 young women (< 50
years) recently diagnosed with breast cancer, exploring information requirements
and experiences of genetic testing decision making; stage 3, three focus groups
(N = 21) exploring preferences for information presentation and prioritisation of
content; stage 4, think-aloud interviews to refine the prototype (N = 16).
RESULTS: Participants wanted information regarding the pros and cons of testing,
the testing process and implications for their family, presented in a way that
allowed them to choose the level of detail they required. They preferred the term
'altered gene', valued a medical word definition function and warnings before
accessing sensitive information. CONCLUSION: Participants valued the decision
support tool, the accessibility of the information and its clinical endorsement.
The decision support tool has considerable clinical utility as an adjunct to
genetic counselling or for use in busy oncology clinics where formal genetic
counselling may be unavailable.
PMID- 29955975
TI - Ambivalence over emotional expression and physical functioning and limitations:
mediating and moderating effects of PTSD symptoms and acculturation among Chinese
breast cancer survivors.
AB - OBJECTIVE: The psychosocial correlates of physical functioning and limitations
are not well-known among Chinese breast cancer survivors. Previous research
suggests a link between ambivalence over emotional expression (AEE) and physical
functioning. The current study built upon this research by examining post
traumatic stress symptoms (PTSS) as a mechanism. Further, we also examined the
moderating effects of mainstream cultural orientation. To this end, we tested
study hypotheses using moderated mediation models. METHODS: Participants were 96
Chinese-speaking breast cancer survivors in the USA. Participants were diagnosed
within the past five years with stages 0-III breast cancer. Participants
completed questionnaires related to AEE, PTSS, SF-36 physical functioning, and
role limitations due to physical health subscales, and acculturation. RESULTS:
Results from moderated mediation models provided support for study hypotheses.
AEE was positively related to overall PTSS and its three subscales (i.e., re
experiencing symptoms, avoidance, and arousal). Further, PTSS and the three
subscales were negatively related to physical functioning and positively related
to role limitations due to physical health. The indirect effects of AEE on
physical functioning and role limitations due to physical health through PTSS and
the three subscales were significant. Moderated mediation models showed that the
indirect effects of AEE on physical functioning through PTSS and the re
experiencing subscale were stronger for those high, compared to low, in
mainstream culture orientation. CONCLUSION: Those with high AEE experience had
worse physical functioning and greater role limitations due to increased PTSS.
However, the indirect effects were stronger for those who endorse greater
mainstream culture. Implications for results suggest that interventions aimed at
addressing AEE and PTSS may help alleviate physical health problems especially
those high in mainstream culture orientation.
PMID- 29955976
TI - On the effect of the thermostat in non-equilibrium molecular dynamics
simulations.
AB - The numerical investigation of the statics and dynamics of systems in non
equilibrium in general, and under shear flow in particular, has become more and
more common. However, not all the numerical methods developed to simulate
equilibrium systems can be successfully adapted to out-of-equilibrium cases. This
is especially true for thermostats. Indeed, even though thermostats developed to
work under equilibrium conditions sometimes display good agreement with rheology
experiments, their performance rapidly degrades beyond weak dissipation and small
shear rates. Here we focus on gauging the relative performances of three
thermostats, Langevin, dissipative particle dynamics, and Bussi-Donadio
Parrinello under varying parameters and external conditions. We compare their
effectiveness by looking at different observables and clearly demonstrate that
choosing the right thermostat (and its parameters) requires a careful evaluation
of, at least, temperature, density and velocity profiles. We also show that small
modifications of the Langevin and DPD thermostats greatly enhance their
performance in a wide range of parameters.
PMID- 29955977
TI - Spatio-temporal release of NGF and GDNF from multi-layered nanofibrous
bicomponent electrospun scaffolds.
AB - Scaffolds capable of providing dual neurotrophic factor (NTF) delivery with
different release kinetics, spatial delivery of NTFs at different loci and
topographical guidance are promising for enhanced peripheral nerve regeneration.
In this study, we have designed and fabricated multi-layered aligned-fiber
scaffolds through combining emulsion electrospinning, sequential electrospinning
and high-speed electrospinning (HS-ES) to modulate the release behavior of glial
cell line-derived growth factor(GDNF) and nerve growth factor (NGF). GDNF and NGF
were incorporated into poly(lactic-co-glycolic acid) (PLGA) fibers and poly(D,L
lactic acid) (PDLLA) fibers, respectively. Aligned fibers were obtained in each
layer of multi-layered scaffolds and relatively thick tri-layered and tetra
layered scaffolds with controlled layer thickness were obtained. Their
morphology, structure, properties, and the in vitro release of growth factors
were examined. Dual and spatio-temporal release of GDNF and NGF with different
release kinetics from multi-layered scaffolds was successfully demonstrated. High
separation efficiency by PDLLA fibrous barrier layer for spatial neurotrophic
factor delivery from both tri-layered scaffolds and tetra-layered scaffolds was
achieved.
PMID- 29955978
TI - Carbon and nitrogen mineralization in Vertisol as mediated by type and placement
method of residue.
AB - Selection of appropriate residue application method is essential for better use
of biomass for soil and environmental health improvement. A laboratory incubation
experiment was conducted for 75 days to investigate C and N mineralization of
residues of soybean (Glycine max L.), chickpea (Cicer arietinum L.), maize (Zea
mays L.), and wheat (Triticum aestivum L.) placed on the soil surface and
incorporated into the soil. The residue of soybean and chickpea had a greater
decomposition rate than that of maize and wheat, despite of their placements.
Higher rate of decomposition of the residue of soybean and chickpea was recorded
when it was kept on the soil surface while soil incorporation of residue of wheat
and maize resulted in faster decomposition. Therefore, these findings could be
used as guidelines for management of crop residue application in farmland to
improve soil and environmental quality.
PMID- 29955979
TI - Improvement in the photoelectric conversion efficiency for the flexible fibrous
dye-sensitized solar cells.
AB - A dye-sensitized and flexible TiO2 fiber with multilayer structure was prepared
by using brush method as the photoanode in the efficient flexible fibrous dye
sensitized solar cells (FFDSSCs) to avoid electronic recombination and improve
the electronic capture efficiency. The composite Pt counter electrode,
preparation from the surface modification of the electrodeposited Pt wire by
using a simple one-step thermal decomposition approach of H2PtCl6 isopropanol and
n-butyl alcohol (volume ratio = 1:1) solution, provided a significant improvement
in electrocatalytic activity, which was confirmed by extensive electrochemical
tests. The FFDSSC assembled with the fiber-shaped TiO2 photoanode and the
composite Pt counter electrode achieves an enhanced photoelectric conversion
efficiency of 6.35%, higher than that of the FFDSSC with monolayer fibrous TiO2
photoanode and electrodeposited Pt wire counter electrode. More importantly, the
photoelectric conversion efficiency of 6.35% is comparable to that of the FFDSSC
based on the pure Pt wire counter electrode (6.32%). The FFDSSC with high
elasticity, flexibility, and stretchability can adapt to complex mechanical
deformations, which is of great significance for the development of wearable
electronics in the future.
PMID- 29955980
TI - Assessment of geospatial and hydrochemical interactions of groundwater quality,
southwestern Nigeria.
AB - Groundwater pollution resulting from anthropogenic activities and poor effluent
management is on the rise in Nigeria. Hence, groundwater used for domestic
purposes is questionable and therefore calls for scientific scrutiny.
Investigation of hydrochemical interactions and quality of groundwater resource
is essential in order to monitor and identify sources of water pollutants. As a
result, groundwater samples were collected from 21 locations in Abeokuta South,
Nigeria and analyzed for physicochemical parameters using standard methods.
Results obtained were subjected to hydrochemical and geospatial analyses. Water
quality parameters investigated exhibited wide variations from location to
location. Fe2+, Mg2+, SO42-, Cl-, total hardness (TH), Mn, Na+, NO3-, SiO2, and
alkalinity exhibited the highest levels of variation with coefficients of
variation of 131.3, 92.8, 83.9, 76.7, 65.9, 64.3, 57.6, 57.2, 57.0, and 52.5,
respectively. The average pH value was 6.76 with 71% of the water samples being
slightly acidic. Na2+, Mg2+, Fe2+, and EC contents exhibited the most violation
of drinking water standards with percent violations of 100, 52.4, 47.6, and
47.6%, respectively. Parameters, such as Mn, Ca2+, NO3-, and CO32-, were within
the WHO guideline values for drinking water in all the samples. The highest level
of significant correlation was found to exist between Na+ and Cl- (r = 0.84,
alpha = 0.01). Six principal components, which explained 83.5% of the variation
in water quality, were extracted with the first (34.1%) and second components
(15.7%) representing the influence of mineral dissolution and anthropogenic
practices, respectively, on the hydrochemistry of the area. Four hydrochemical
clusters were identified with distinctly partitioned water quality. Further
analysis revealed that 38, 29, 24, and 9% of the samples were the Na-K-HCO3, Na-K
Cl-SO4, Ca-Mg-HCO3, and Ca-Mg-Cl-SO4 types, respectively. Anthropogenic
activities are increasing threat to groundwater quality in the study location and
therefore call for urgent attention. There is also a need for routine monitoring
of groundwater in Abeokuta.
PMID- 29955981
TI - Update on Inclusion Body Myositis.
AB - PURPOSE OF REVIEW: While sporadic inclusion body myositis (sIBM) is the most
common acquired muscle disease after age 50, the pathogenesis of this disease is
still poorly understood. In this review, we discuss our current state of
knowledge in sIBM and provide an update on our current understanding of its
pathophysiology and management. RECENT FINDINGS: Lines of evidence in support of
an inflammatory pathogenesis include inflammatory infiltrates in the target
organ, NFkappaB activation, cytokine response, MHC I upregulation, and cN1A
antibody. Refractoriness to immunotherapies has led to suggestion of a
degenerative pathophysiology. Evidence for impaired protein homeostasis with
misfolding burden is coupled with findings of endoplasmic reticulum stress,
proteasome dysfunction, and mitochondrial lesion. Recent treatment trials have
focused more on correcting the degenerative process or muscle growth rather than
controlling the inflammation. There has been growing evidence toward degeneration
as the primary process in sIBM. This is consistent with the refractory nature of
this disease. Improving our understanding of this disease pathogenesis will
propel efforts to find an effective therapy.
PMID- 29955982
TI - Soil carbon and nitrogen accumulation in residential lawns of the Salt Lake
Valley, Utah.
AB - Urban lawn ecosystems are widespread across the United States, with fertilization
rates commonly exceeding plant nitrogen (N) uptake rates. While urban soils have
been shown to accumulate C and N over time, the long-term balance of N inputs and
losses from lawn soils remains largely uncertain. We sampled residential lawn
soils aged 7-100 years in the Salt Lake City metropolitan area as a means of
inferring changes in total nitrogen (TN) content, organic carbon (OC) content,
C:N ratio, and delta15N of bulk soil over time. Core-integrated (0-40 cm) TN and
OC stocks increased linearly by 2.39 g N m-2 year-1 and 29.8 g OC m-2 year-1 over
the 100-year chronosequence. TN and OC percent were also negatively correlated
with elevation. Multiple linear regression models including housing age and
elevation as covariates, explained 68 and 62% of variability in TN and OC stocks
respectively. delta15N increased with housing age, soil depth, and clay content,
suggesting N removal over time, especially in poorly drained soils. We quantified
potential hydrologic and gaseous N losses over time by comparing observed N
accumulation to different historic fertilization scenarios. Modeling and isotopic
results suggest that, while soil N has accumulated over time, the majority of N
added to lawns in the Salt Lake Valley over 50 years of fertilization was likely
lost from surface soils via denitrification or leaching.
PMID- 29955983
TI - Stable isotope ecology of black rhinos (Diceros bicornis) in Kenya.
AB - Stable isotope and elemental ratios in hair are influenced by the environment,
including both climate and geology. Stable carbon isotopes can be used to give
estimates of the C4/CAM fraction of diets of herbivorous mammals; stable nitrogen
isotopes are related to the local water deficit; strontium isotopes are
determined by the local geology. We studied hair from rhinos in Kenya to
determine spatial patterns in delta13C, delta15N, and 87Sr/86Sr ratios. The
samples of rhino hair were collected during Kenya Wildlife Service translocation
or veterinary activities. delta13C values showed diets dominated by C3 foods, but
in some regions the diet, at least seasonally, contained significant quantities
(i.e., > ca. 20%) of C4/CAM foods. delta15N values were related to water deficit,
with higher delta15N values in regions with high water deficit. 87Sr/86Sr isotope
ratios were found to be related to the local geological substrate suggesting that
87Sr/86Sr isotope ratios are provisionally useful for determining the origins of
illegal wildlife materials in Kenya and elsewhere in Africa.
PMID- 29955984
TI - Applying the principles of isotope analysis in plant and animal ecology to
forensic science in the Americas.
AB - The heart of forensic science is application of the scientific method and
analytical approaches to answer questions central to solving a crime: Who, What,
When, Where, and How. Forensic practitioners use fundamentals of chemistry and
physics to examine evidence and infer its origin. In this regard, ecological
researchers have had a significant impact on forensic science through the
development and application of a specialized measurement technique-isotope
analysis-for examining evidence. Here, we review the utility of isotope analysis
in forensic settings from an ecological perspective, concentrating on work from
the Americas completed within the last three decades. Our primary focus is on
combining plant and animal physiological models with isotope analyses for source
inference. Examples of the forensic application of isotopes-including stable
isotopes, radiogenic isotopes, and radioisotopes-span from cotton used in
counterfeit bills to anthrax shipped through the U.S. Postal Service and from
beer adulterated with cheap adjuncts to human remains discovered in shallow
graves. Recent methodological developments and the generation of isotope
landscapes, or isoscapes, for data interpretation promise that isotope analysis
will be a useful tool in ecological and forensic studies for decades to come.
PMID- 29955985
TI - Dew-induced transpiration suppression impacts the water and isotope balances of
Colocasia leaves.
AB - Foliar uptake of water from the surface of leaves is common when rainfall is
scarce and non-meteoric water such as dew or fog is more abundant. However, many
species in more mesic environments have hydrophobic leaves that do not allow the
plant to uptake water. Unlike foliar uptake, all species can benefit from dew- or
fog-induced transpiration suppression, but despite its ubiquity, transpiration
suppression has so far never been quantified. Here, we investigate the effect of
dew-induced transpiration suppression on the water balance and the isotope
composition of leaves via a series of experiments. Characteristically,
hydrophobic leaves of a tropical plant, Colocasia esculenta, are misted with
isotopically enriched water to reproduce dew deposition. This species does not
uptake water from the surface of its leaves. We measure leaf water isotopes and
water potential and find that misted leaves exhibit a higher water potential and
a more depleted water isotope composition than dry leaves, suggesting a ~ 30%
decrease in transpiration rate compared to control leaves. We propose three
possible mechanisms governing the interaction of water droplets with leaf energy
balance: increase in albedo from the presence of dew droplets, decrease in leaf
temperature from the evaporation of dew, and local decrease in vapor pressure
deficit. Comparing previous studies on foliar uptake to our results, we conclude
that transpiration suppression has an effect of similar amplitude, yet opposite
sign to foliar uptake on leaf water isotopes.
PMID- 29955986
TI - Distinctions in heterotrophic and autotrophic-based metabolism as recorded in the
hydrogen and carbon isotope ratios of normal alkanes.
AB - The hydrogen isotope values of n-alkanes (delta2Hn-alkane) reflect a plant's
water source and water relations, while the carbon isotope values (delta13Cn
alkane) relate to a plant's carbon metabolism and response to environmental
conditions. However, the isotopic dynamics of the transition from heterotrophic
to autotrophic metabolism during foliar development on delta2Hn-alkane and
delta13Cn-alkane remain unclear. Here, we monitored delta2Hn-alkane and delta13Cn
alkane across a growing season from Betula occidentalis, Populus angustifolia,
and Acer negundo. In addition, we compiled delta2H values of atmospheric vapor,
leaf water, xylem water, and stream water as well as delta13C values of bulk leaf
tissue (delta13Cbulk). We found delta2Hn-alkane and delta13Cn-alkane varied with
leaf development and indicated that the majority of wax development occurred
during the initial growing season. The patterns in delta2Hn-alkane were broadly
consistent between species and with previous studies; however, each species had a
unique final delta2Hn-alkane value. The delta13Cbulk for all species demonstrated
a characteristic 13C-enrichment during the initial growing season, followed by
13C-depletion, while delta13Cn-alkane did not exhibit a consistent trend between
the species. These delta13C data suggested a decoupling of the isotopic inputs
between n-alkanes and photosynthetic leaf tissue. When coupled with delta2Hn
alkane, these data suggested that the precursor compounds utilized in initial
production of n-alkanes might be variable and possibly indicated that the stored
precursors used for initial leaf tissue and wax production originated from
different sources. Nonetheless, these data indicated that the isotopic signatures
of n-alkanes relate to a mixture of precursors, but only during a distinct period
of leaf ontogeny.
PMID- 29955987
TI - Inferring the source of evaporated waters using stable H and O isotopes.
AB - Stable isotope ratios of H and O are widely used to identify the source of water,
e.g., in aquifers, river runoff, soils, plant xylem, and plant-based beverages.
In situations where the sampled water is partially evaporated, its isotope values
will have evolved along an evaporation line (EL) in delta2H/delta18O space, and
back-correction along the EL to its intersection with a meteoric water line (MWL)
has been used to estimate the source water's isotope ratios. Here, we review the
theory underlying isotopic estimation of source water for evaporated samples
(iSWE). We note potential for bias from a commonly used regression-based approach
for EL slope estimation and suggest that a model-based approach may be preferable
if assumptions of the regression approach are not valid. We then introduce a
mathematical framework that eliminates the need to explicitly estimate the EL-MWL
intersection, simplifying iSWE analysis and facilitating more rigorous
uncertainty estimation. We apply this approach to data from the US EPA's 2007
National Lakes Assessment. We find that data for most lakes are consistent with a
water source similar to annual runoff, estimated from monthly precipitation and
evaporation within the lake basin. Strong evidence for both summer- and winter
biased sources exists, however, with winter bias pervasive in most snow-prone
regions. The new analytical framework should improve the rigor of iSWE in
ecohydrology and related sciences, and our initial results from US lakes suggest
that previous interpretations of lakes as unbiased isotope integrators may only
be valid in certain climate regimes.
PMID- 29955988
TI - Arctic plant ecophysiology and water source utilization in response to altered
snow: isotopic (delta18O and delta2H) evidence for meltwater subsidies to
deciduous shrubs.
AB - Warming-linked woody shrub expansion in the Arctic has critical consequences for
ecosystem processes and climate feedbacks. The snow-shrub interaction model has
been widely implicated in observed Arctic shrub increases, yet equivocal
experimental results regarding nutrient-related components of this model have
highlighted the need for a consideration of the increased meltwater predicted in
expanding shrub stands. We used a 22-year snow manipulation experiment to
simultaneously address the unexplored role of snow meltwater in arctic plant
ecophysiology and nutrient-related components of the snow-shrub hypothesis. We
coupled measurements of leaf-level gas exchange and leaf tissue chemistry (%N and
delta13C) with an analysis of stable isotopes (delta18O and delta2H) in soil
water, precipitation, and stem water. In deeper snow areas photosynthesis,
conductance, and leaf N increased and delta13C values decreased in the deciduous
shrubs, Betula nana and Salix pulchra, and the graminoid, Eriophorum vaginatum,
with the strongest treatment effects observed in deciduous shrubs, consistent
with predictions of the snow-shrub hypothesis. We also found that deciduous
shrubs, especially S. pulchra, obtained much of their water from snow melt early
in the growing season (40-50%), more than either E. vaginatum or the evergreen
shrub, Rhododendron tomentosum (Ledum palustre). This result provides the basis
for adding a meltwater-focused feedback loop to the snow-shrub interaction model
of shrub expansion in the Arctic. Our results highlight the critical role of
winter snow in the ecophysiology of Arctic plants, particularly deciduous shrubs,
and underline the importance of understanding how global warming will affect the
Arctic winter snowpack.
PMID- 29955989
TI - Assessing the interplay between canopy energy balance and photosynthesis with
cellulose delta18O: large-scale patterns and independent ground-truthing.
AB - There are few whole-canopy or ecosystem scale assessments of the interplay
between canopy temperature and photosynthesis across both spatial and temporal
scales. The stable oxygen isotope ratio (delta18O) of plant cellulose can be used
to resolve a photosynthesis-weighted estimate of canopy temperature, but the
method requires independent confirmation. We compare isotope-resolved canopy
temperatures derived from multi-year homogenization of tree cellulose delta18O to
canopy-air temperatures weighted by gross primary productivity (GPP) at multiple
sites, ranging from warm temperate to boreal and subalpine forests. We also
perform a sensitivity analysis for isotope-resolved canopy temperatures that
showed errors in plant source water delta18O lead to the largest errors in canopy
temperature estimation. The relationship between isotope-resolved canopy
temperatures and GPP-weighted air temperatures was highly significant across
sites (p < 0.0001, R2 = 0.82), thus offering confirmation of the isotope
approach. The previously observed temperature invariance from temperate to boreal
biomes was confirmed, but the greater elevation of canopy temperature above air
temperature in the boreal forest was not. Based on the current analysis, we
conclude that canopy temperatures in the boreal forest are as warm as those in
temperate systems because day-time-growing-season air temperatures are similarly
warm.
PMID- 29955990
TI - Leaf stable isotopes suggest shared ancestry is an important driver of functional
diversity.
AB - Plant physiological strategies of carbon (C) and nitrogen (N) uptake and
metabolism are often regarded as outcomes of environmental selection. This is
likely true, but the role of evolutionary history may also be important in
shaping patterns of functional diversity. Here, we used leaf C and N stable
isotope ratios (delta13C, delta15N) as integrators of physiological processes to
assess the relative roles of phylogenetic history and environment in a diverse
group of Ericaceae species native to North America. We found strong phylogenetic
signal in both leaf delta13C and delta15N, suggesting that close relatives have
similar physiological strategies. The signal of phylogeny was generally stronger
than that of the local environment. However, within some specialized environments
(e.g., wetlands, sandy soils), we found environmental effects and/or niche
conservatism. Phylogenetic signal in delta13C appears to be most closely related
to the constraints on metabolic demand and supply of C, and delta15N appears to
be most strongly related to mycorrhizal associations within the family.
PMID- 29955991
TI - Seasonal controls on ecosystem-scale CO2 and energy exchange in a Sonoran Desert
characterized by the saguaro cactus (Carnegiea gigantea).
AB - Episodic precipitation pulses are important for driving biological activity in
desert ecosystems. The pattern of precipitation, including the size of rain
events and the duration of time between events, can influence ecosystem net CO2
exchange (NEE) by shifting the balance between ecosystem photosynthesis and
respiration. Our objective was to measure the response of NEE and its major
components, to seasonal variation in precipitation and other environmental
conditions. The study was conducted at a site, where 40-60% of annual
precipitation comes from the North American Monsoon that typically brings rain in
July-September, a time period when temperatures are near the seasonal peak. The
results were compared to a model of the expected responses of NEE to seasonal
changes in precipitation and temperature. We measured NEE using the eddy
covariance technique during September 2015-August 2016. The ecosystem showed
large (fivefold) seasonal variation in maximum photosynthesis and ecosystem
respiration rate at 10 degrees C that corresponded to seasonal variation in
precipitation and temperature. Ecosystem respiratory activity exceeded
photosynthetic activity, so the ecosystem was a net source of CO2 to the
atmosphere during June-October, a period that included monsoon rain inputs. Only
during the winter months (November-March) did photosynthesis exceed respiration,
resulting in net ecosystem carbon sequestration. The ecosystem recorded a net
loss of 10 g C m-2 year-1, which was likely caused by below normal annual
precipitation during the study. Our results illustrated the important interaction
between seasonal variation in precipitation and temperature in controlling the
ecosystem carbon budget.
PMID- 29955994
TI - Preface: Honoring the career of Professor James R. Ehleringer.
PMID- 29955993
TI - Does sexual dimorphism predispose dioecious riparian trees to sex ratio
imbalances under climate change?
AB - Environmental changes have resulted in significant declines in native riparian
forests that are comprised largely of dioecious tree taxa, including boxelder and
iconic cottonwood/willow gallery forests. Dioecious species may be especially
vulnerable to the effects of climate change given that they often exhibit skewed
sex ratios that are reinforced by physiological and morphological specialization
of each sex to specific microhabitats. A comprehensive data synthesis suggests
that male individuals of boxelder and cottonwood taxa have a higher
representation on dry microhabitats than females and are less physiologically
sensitive to increased aridity than co-occurring females. Consequently, extreme
male-biased sex ratios are possible under future climate conditions that could
reduce population fitness below a sustainable threshold. Riparian willows, on the
other hand, generally do not express obvious sexual dimorphism in habitat
preference or physiological sensitivity to aridity. Thus, it is unclear whether
climate change will impact population structure of willows in ways that parallel
other dioecious riparian tree taxa. Future riparian tree restoration programs
should aim to maintain future sex ratio balance that maximizes population fitness
under projected hydro-climatological conditions. Recent advances in genomics will
likely provide the critical tools for early sex determination in pre-reproductive
trees across riparian tree species such that sex ratio balance could be targeted
during initial stages of restoration, along with adaptations for drought
tolerance and other key traits that are essential for survival under future
conditions.
PMID- 29955992
TI - Some like it hot: the physiological ecology of C4 plant evolution.
AB - The evolution of C4 photosynthesis requires an intermediate phase where
photorespiratory glycine produced in the mesophyll cells must flow to the
vascular sheath cells for metabolism by glycine decarboxylase. This glycine flux
concentrates photorespired CO2 within the sheath cells, allowing it to be
efficiently refixed by sheath Rubisco. A modest C4 biochemical cycle is then
upregulated, possibly to support the refixation of photorespired ammonia in
sheath cells, with subsequent increases in C4 metabolism providing incremental
benefits until an optimized C4 pathway is established. 'Why' C4 photosynthesis
evolved is largely explained by ancestral C3 species exploiting photorespiratory
CO2 to improve carbon gain and thus enhance fitness. While photorespiration
depresses C3 performance, it produces a resource (photorespired CO2) that can be
exploited to build an evolutionary bridge to C4 photosynthesis. 'Where' C4
evolved is indicated by the habitat of species branching near C3-to-C4
transitions on phylogenetic trees. Consistent with the photorespiratory bridge
hypothesis, transitional species show that the large majority of > 60 C4 lineages
arose in hot, dry, and/or saline regions where photorespiratory potential is
high. 'When' C4 evolved has been clarified by molecular clock analyses using
phylogenetic data, coupled with isotopic signatures from fossils. Nearly all C4
lineages arose after 25 Ma when atmospheric CO2 levels had fallen to near current
values. This reduction in CO2, coupled with persistent high temperature at low-to
mid-latitudes, met a precondition where photorespiration was elevated, thus
facilitating the evolutionary selection pressure that led to C4 photosynthesis.
PMID- 29955995
TI - Millennial-scale tree-ring isotope chronologies from coast redwoods provide
insights on controls over California hydroclimate variability.
AB - To understand drivers of hydroclimate variability in north-coastal California, we
obtained tree cross-sections from eleven coastal redwoods (mean age of 1232 years
old) from the northern half of the species range. Tree rings from eight trees
were cross-dated and sampled at sub-annual resolution for carbon isotope
discrimination (Delta13C) and oxygen isotope composition (delta18O). Tree-ring
Delta13C and delta18O, compared to modern climate data, demonstrate these signals
primarily record summertime hydroclimate variability-primarily through variables
associated with evaporative conditions and/or precipitation. Our 1100-year stable
isotope chronologies showed that north-coastal California did not undergo the
megadroughts observed elsewhere in California and the western United States. This
result implicates extended periods of low winter precipitation, rather than
growing season evaporation, as the primary driver of previous megadroughts across
California and neighboring regions. Compared to cool conditions prevailing over
the Northern Hemisphere during the Little Ice age (1301-1875 of the common era,
CE), the frequency of isotopic events of a certain magnitude was greater during
periods with warmer Northern Hemisphere temperatures such as the Medieval Climate
Anomaly (900-1300 CE) and the modern period (1876 to present). This association
between tree-ring isotopic variability and long-term shifts in temperatures is
consistent with the expected patterns in mid-latitude hydroclimate variability
expected from arctic amplification (i.e., shifts in equator-to-pole temperature
differences that modify jet stream speed and amplitude) or amplified quasi
resonant wave activity (i.e., wave-patterns in high-altitude winds that become
"trapped" within a certain pattern, thereby producing a longer-duration periods
of drought or wetness) across mid-latitudes during the boreal summer.
PMID- 29955996
TI - Ecophysiological plasticity of Amazonian trees to long-term drought.
AB - Episodic multi-year droughts fundamentally alter the dynamics, functioning, and
structure of Amazonian forests. However, the capacity of individual plant species
to withstand intense drought regimes remains unclear. Here, we evaluated
ecophysiological responses from a forest community where we sampled 83 woody
plant species during 5 years of experimental drought (throughfall exclusion) in
an eastern Amazonian terra firme forest. Overall, the experimental drought
resulted in shifts of some, but not all, leaf traits related to photosynthetic
carbon uptake and intrinsic water-use efficiency. Leaf delta13C values increased
by 2-30/00 within the canopy, consistent with increased diffusional constraints
on photosynthesis. Decreased leaf C:N ratios were also observed, consistent with
lower investments in leaf structure. However, no statistically significant
treatment effects on leaf nitrogen content were observed, consistent with a lack
of acclimation in photosynthetic capacity or increased production of nitrogen
based secondary metabolites. The results of our study provide evidence of robust
acclimation potential to drought intensification in the diverse flora of an
Amazonian forest community. The results reveals considerable ability of several
species to respond to intense drought and challenge commonly held perspectives
that this flora has attained limited adaptive plasticity because of a long
evolutionary history in a favorable and stable climate.
PMID- 29955997
TI - Interactions between rising CO2 and temperature drive accelerated flowering in
model plants under changing conditions of the last century.
AB - Past studies have shown that flowering times have accelerated over the last
century. These responses are often attributed to rising temperature, although
short-term field experiments with warming treatments have under-estimated
accelerations in flowering time that have been observed in long-term field
surveys. Thus, there appears to be a missing factor(s) for explaining accelerated
flowering over the last century. Rising atmospheric CO2 concentration ([CO2]) is
a possible candidate, and its contributions to affecting flowering time over
historic periods are not well understood. This is likely because rising [CO2] is
confounded with temperature in the field and preindustrial [CO2] studies are
relatively rare. To address this, we tested the individual and interactive
effects of rising [CO2] and temperature between preindustrial and modern periods
on flowering time in the model system, Arabidopsis thaliana. We used a variety of
genotypes originating from diverse locations, allowing us to test intraspecific
responses to last-century climate change. We found that accelerated flowering
time between the full-preindustrial and full-modern treatments was mainly driven
by an interaction between rising [CO2] and temperature, rather than through the
individual effects of either factor in isolation. Furthermore, accelerated
flowering time was driven by enhanced plant growth rates and not through changes
in plant size at flowering. Thus, the interaction between rising [CO2] and
temperature may be key for explaining large accelerations in flowering times that
have been observed over the last century and that could not be explained by
rising temperature alone.
PMID- 29955998
TI - A tale of ENSO, PDO, and increasing aridity impacts on drought-deciduous shrubs
in the Death Valley region.
AB - Germination, establishment, phenology, and death among three drought-deciduous
shrubs were influenced by ENSO/PDO and precipitation, based on 37 years of annual
surveys. Encelia farinosa forms near monospecific stands on slopes, whereas E.
frutescens and Ambrosia salsola dominate wash habitats. All shrubs exhibited
phenological coherence. While germination, establishment, and mortality patterns
were similar among wash species, these dynamics contrasted with E. farinosa on
slopes. Germination was associated with El Nino years. Slope plant establishment
was dependent on precipitation in the subsequent year, but not evidently so in
wash species. Major mortality events were episodic, with Encelia mortality just
as likely to occur in years with below or above average precipitation. In both
Encelia species, mortality was associated with transitions to a cold PDO phase.
In E. frutescens this response was more rapid, whereas in E. farinosa mortality
lagged 1 year, resulting in contrasting slope-wash mortality patterns. 50% of
newly established shrubs died within 5, 5, and 18 years for E. frutescens, E.
farinosa, and A. salsola, respectively. The 90% mortality ages were 26 years for
E. frutescens, 24 years for E. farinosa, and 51 years for A. salsola. While
maximum life expectancies are unknown, estimated maximum life expectancies were
56, 66, and 86 years for E. frutescens, E. farinosa, and A. salsola,
respectively. Overall, as the climate has become more arid over the past four
decades, the populations in both slope and wash habitats have exhibited similar
responses: reduced shrub abundances and reduced total supportable leaf areas.
PMID- 29955999
TI - Revision strategy and follow-up for implant failure in a case of combined
anterior and posterior reconstruction after three-level en bloc vertebral body
replacement and replacement of the aorta for chondrosarcoma of the thoracic
spine.
AB - OBJECTIVE: In 2013, we reported a case of combined anterior and posterior
reconstruction after three-level en bloc vertebral body replacement and
replacement of the aorta for chondrosarcoma of the thoracic spine. Eight years
after, we observed an implant failure and now report on revision strategy and 2
year follow-up (f/u) after revision. METHODS: We report about the 2-year f/u of
the same now 51-year-old gravedigger who needed to undergo revision surgery after
implant failure. We did a combined anterior and posterior correction vertebral
interbody fusion by (1) removal of broken screws in Th9 and L2, removal of broken
titanium bars, correction of kyphosis, enhancement of the vertebral interbody
fusion from Th8 to L4 using monoaxial titanium screws and cancellous bone
transplantation and (2) removal of the broken plate and the loose cage,
implantation of a novel expandable PEEK cage from Th11 to L1 and anterior
stabilization from Th9/10 to L2/3, as well as autologous and allogeneic
cancellous bone transplantation. RESULTS: Two years after revision surgery, the
patient presented fully reintegrated without any complains. No painkillers needed
to be taken. Pain was reported with 2 out of 10 on the VAS. CONCLUSION: Both
procedures offer a good primary stabilization with excellent pain reduction and
good return to life. Limited information on long-term survivors is known.
Therefore, the theoretical advantage of a biological solution needs to be checked
in the long-term f/u for consistency.
PMID- 29956000
TI - Reoperation of decompression alone or decompression plus fusion surgeries for
degenerative lumbar diseases: a systematic review.
AB - PURPOSE: The objective of this paper was to compare the reoperation rates, timing
and causes between decompression alone and decompression plus fusion surgeries
for degenerative lumbar diseases through a systematic review of the published
data. METHODS: A search of the literature was conducted on PubMed/MEDLINE, EMBASE
and the Cochrane Collaboration Library. Reports that included reoperations after
decompression alone and/or decompression plus fusion surgeries were selected
using designed eligibility criteria. Comparative analysis of reoperation rates,
timing and causes between the two surgeries was conducted. RESULTS: Thirty-two
retrospective and three prospective studies were selected from 6401 papers of the
literature search. The analysis of data reported in these studies revealed that
both surgeries resulted in similar reoperation rates after the primary surgery.
However, majority of reoperations following the fusion surgeries were due to
adjacent-segment diseases, and following the decompression alone surgeries were
due to the same-segment diseases. Reoperation rates were not found to decrease in
patients operated more recently than those operated in early times. CONCLUSIONS:
Reoperation rates were similar following decompression alone or plus fusion
surgeries for degenerative lumbar diseases. However, different underlying major
causes exist between the two surgeries. There is no evidence showing that the
reoperation rate has a trend to decline with newer surgical techniques used. The
exact mechanisms of reoperation after both surgeries are still unclear. Further
researches are necessary to investigate the mechanisms of reoperation for
improvement of surgical techniques that aim to delay or prevent reoperation after
lumbar surgery. These slides can be retrieved under Electronic Supplementary
Material.
PMID- 29956001
TI - The Management of Lower Urinary Tract Dysfunction in Multiple Sclerosis.
AB - PURPOSE OF REVIEW: Multiple sclerosis (MS) is the most frequent neuroinflammatory
disease of the central nervous system and is commonly associated with lower
urinary tract (LUT) dysfunction. As a consequence, health-related quality of life
is often impaired and the upper urinary tract might be at risk for damage. The
aim of this review is to give an overview of current treatment options for LUT
dysfunction in patients with MS. RECENT FINDINGS: The treatment is tailored to
the type of dysfunction-storage or voiding dysfunction-beginning with
conservative treatment options and ending with invasive therapies and surgery.
Additionally, alternative options, e.g., different intravesical therapies or
cannabinoids, have been evaluated in recent years with promising results. Current
available therapies offer different possible treatments for LUT dysfunction in
patients with MS. They address either voiding or storage dysfunction and
therefore ameliorate LUT symptoms improve quality of life and protect the upper
urinary tract.
PMID- 29956002
TI - Laparoscopic ventral rectopexy in patients with fecal incontinence associated
with rectoanal intussusception: prospective evaluation of clinical, physiological
and morphological changes.
AB - BACKGROUND: Physiological changes after laparoscopic ventral rectopexy (LVR) in
patients with rectoanal intussusception (RAI) remain unclear. This study was
undertaken to evaluate physiological and morphological changes after LVR for RAI,
and to study clinical outcomes following LVR with special reference to fecal
incontinence (FI). METHODS: The study was conducted on patients who had LVR for
RAI between February 2012 and December 2016 at our institution Patients with RAI
and FI were included in the study. Patients with RAI and obstructed defecation
and those with RAI and neurologic FI were not included. The patients had
anorectal manometry preoperatively, and 3, 6, and 12 months postoperatively.
Defecography was performed before and 6 months after the procedure. FI was
evaluated using the Fecal Incontinence Severity Index (FISI). RESULTS: There were
34 patients (median age 77 years (range 60-93) years). Thirty-two patients (94%)
were female and the median number of vaginal deliveries was 2 (range 0-5).
Neither maximum resting pressure nor maximum squeeze pressure increased
postoperatively. There was an overall increase in both defecatory desire volume
(median preoperative 75 ml vs. 90 ml at 12 months; p = 0.002) and maximum
tolerated volume (median preoperative 145 ml vs.175 ml at 12 months; p = 0.002).
Postoperatively, RAI was eliminated in all patients but one, although 13 had
residual rectorectal intussusception found at defecography. There was an overall
reduction in both rectocele size (median preop 29 mm vs. postop 10 mm; p = 0.008)
and pelvic floor descent (median preop 26 mm vs. postop 20 mm; p = 0.005). Twelve
months after surgery, a reduction of at least 50% was observed in the FISI score
for 31 incontinent patients (91%). CONCLUSIONS: LVR for RAI produced adequate
improvement of FI, and successful anatomical correction of RAI was confirmed by
postoperative proctography. Postoperative increase in the rectal volume may have
a positive effect on continence.
PMID- 29956003
TI - Transanal total mesorectal excision (taTME) in a single-surgeon setting:
refinements of the technique during the learning phase.
AB - BACKGROUND: Transanal total mesorectal excision (taTME) is a safe and effective
technique. We have progressively developed a systematic approach in the single
surgeon setting. The aim of this study was to compare our early vs late single
surgeon taTME experience as well as present the technical and logistical
modifications that were crucial to achieve successful implementation of a taTME
program. METHODS: Review of prospectively collected data on 27 patients who had
taTME in June 2015-September 2016 (early cohort) was included and compared with
43 patients who underwent taTME in October 2016-September 2017 (late cohort).
Procedures were performed by a single-surgeon team at Health Sciences North
(Sudbury, Ontario, Canada). Inclusion criteria were T1-3 or downstaged T4 mid-
and low-rectal lesions. Cases of non-neoplastic disease were excluded. Outcomes
assessed included mesorectal integrity, margin status, operative time,
complications, morbidity, length of stay and 30-day readmission. RESULTS: A total
of 70 cases were included. Patients were divided into early (27 patients, 14
males; mean age 60.74 +/- 9.77 years) and late (43 patients, 29 males; mean age
63.48 +/- 10.85 years) cohorts. During the early phase, procedural modifications
including regular takedown of the splenic flexure, intra-corporeal division of
the mesentery, liberal use of a Pfannenstiel incision for extraction, abundant
washing of the surgical field and regular use of the ICG technology were
progressively introduced. There was no mortality nor statistically significant
difference between the early and late cohort in terms of morbidity (33.3 vs 39.4%
p = 0.727), anastomotic leak (14.8 vs 4.6% p = 0.19), operating time (5.05 +/-
1.26 vs 4.96 +/- 1.14 h p = 0.755), length of stay (4.0 +/- 2.54 vs 4.81 +/- 3.63
days p = 0.394) and CRM negative margin (96.3 vs. 97.7% p = 0.999), and no
incomplete specimens were obtained on either cohort. CONCLUSIONS: This study
confirms the safety and effectiveness of single-surgeon implementation of taTME
technique. Technical challenges experienced in this setting were not obstacles
for further refinement and to establish a tendency towards better outcomes.
Overcoming technical challenges is possible, familiarity with taTME is slow yet
progressive, and improvement tends to occur with experience.
PMID- 29956004
TI - HCV-negative mixed cryoglobulinemia and kidney involvement: in-depth review on
physiopathological and histological bases.
AB - Type II mixed cryoglobulinemia without evidence of HCV infection but rather with
renal involvement has been occasionally described. The pathogenesis of
cryoglobulinemic kidney disease is most likely related to immune complex
deposition including cryoglobulins, and cryoaggregation after cold exposure could
play a pivotal role in clinical expression of cryoglobulinemia. In these cases,
acute kidney injury and proteinuria remain the most frequent clinical expression
of a cryoglobulinemic glomerulonephritis. Type II cryoglobulinemia with the
laboratory finding of both monoclonal and polyclonal cryoglobulins is the most
prevalent bio-humoral pattern among HCV-negative phenotypes with renal
involvement, while type III cryoglobulinemia with polyclonal Ig is rare.
Histological data in renal biopsies support the hypothesis that regardless of the
HCV status cryoglobulinemia vasculitis share the same frequent pathological
finding of membranoproliferative glomerulonephritides, but other histological
patterns have also been observed in a minority of cases. In HCV-negative mixed
cryoglobulinaemia, the paraneoplastic origin of the immune dysfunction should be
ruled out and sporadic cases have been reported, while there is no cumulative
evidence on the prevalence of these tumour-associated manifestations. Moving from
the classification criteria and the etiopathogenesis of mixed cryoglobulinaemia,
we provide a comprehensive review of the literature on the appearance of the
disease with kidney injury in association with malignancies or autoimmune
disorders without HCV coexistence.
PMID- 29956005
TI - Comprehensive genetic testing in children with a clinical diagnosis of ARPKD
identifies phenocopies.
AB - BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is genetically
one of the least heterogeneous ciliopathies, resulting primarily from mutations
of PKHD1. Nevertheless, 13-20% of patients diagnosed with ARPKD are found not to
carry PKHD1 mutations by sequencing. Here, we assess whether PKHD1 copy number
variations or second locus mutations explain these cases. METHODS: Thirty-six
unrelated patients with the clinical diagnosis of ARPKD were screened for PKHD1
point mutations and copy number variations. Patients without biallelic mutations
were re-evaluated and screened for second locus mutations targeted by the
phenotype, followed, if negative, by clinical exome sequencing. RESULTS: Twenty
eight patients (78%) carried PKHD1 point mutations, three of whom on only one
allele. Two of the three patients harbored in trans either a duplication of exons
33-35 or a large deletion involving exons 1-55. All eight patients without PKHD1
mutations (22%) harbored mutations in other genes (PKD1 (n = 2), HNF1B (n = 3),
NPHP1, TMEM67, PKD1/TSC2). Perinatal respiratory failure, a kidney length > +4SD
and early-onset hypertension increase the likelihood of PKHD1-associated ARPKD. A
patient compound heterozygous for a second and a last exon truncating PKHD1
mutation (p.Gly4013Alafs*25) presented with a moderate phenotype, indicating that
fibrocystin is partially functional in the absence of its C-terminal 62 amino
acids. CONCLUSIONS: We found all ARPKD cases without PKHD1 point mutations to be
phenocopies, and none to be explained by biallelic PKHD1 copy number variations.
Screening for copy number variations is recommended in patients with a
heterozygous point mutation.
PMID- 29956006
TI - Clinical experience with the use of ferric citrate as a phosphate binder in
pediatric dialysis patients.
AB - BACKGROUND: Ferric citrate, an iron-based phosphate binder, has been shown to
improve both hyperphosphatemia and iron deficiency in adult chronic kidney
disease patients, but its use in the pediatric dialysis population has not been
described. METHODS: This is a retrospective analysis of 11 unselected pediatric
dialysis patients who received ferric citrate as a phosphate binder between 2015
and 2017. Time-averaged laboratory values were compared pre- and post-ferric
citrate initiation using the Wilcoxon signed-rank test. RESULTS: The median age
of this cohort was 13 years old (range 4-17 years old). Five patients were on
hemodialysis, and six patients were on peritoneal dialysis. The median duration
of ferric citrate therapy was 214 days (range 39-654 days), with a median time
averaged ferric citrate dose of 3.5 tablets per day (range 1.5-8.4 tablets per
day). Compared to the pre-ferric citrate period, ferric citrate treatment was
associated with decreased serum phosphate (6.5 to 5.2 mg/dl, p = 0.014),
decreased phosphate age-related standard deviation score (SDS) (2.3 to 0.9, p =
0.019), increased transferrin saturation (26 to 34%, p = 0.049), increased
ferritin (107 to 230 ng/ml, p = 0.074), and maintenance of hematocrit.
CONCLUSIONS: In pediatric dialysis patients, ferric citrate may be able to
concurrently lower phosphate levels and treat iron deficiency. However, larger
studies are needed to further evaluate safety and efficacy in the pediatric
chronic kidney disease population.
PMID- 29956007
TI - An Efficient Mutual Authentication Framework for Healthcare System in Cloud
Computing.
AB - The increasing role of Telecare Medicine Information Systems (TMIS) makes its
accessibility for patients to explore medical treatment, accumulate and approach
medical data through internet connectivity. Security and privacy preservation is
necessary for medical data of the patient in TMIS because of the very perceptive
purpose. Recently, Mohit et al.'s proposed a mutual authentication protocol for
TMIS in the cloud computing environment. In this work, we reviewed their protocol
and found that it is not secure against stolen verifier attack, many logged in
patient attack, patient anonymity, impersonation attack, and fails to protect
session key. For enhancement of security level, we proposed a new mutual
authentication protocol for the similar environment. The presented framework is
also more capable in terms of computation cost. In addition, the security
evaluation of the protocol protects resilience of all possible security
attributes, and we also explored formal security evaluation based on random
oracle model. The performance of the proposed protocol is much better in
comparison to the existing protocol.
PMID- 29956008
TI - Sudomotor function testing by electrochemical skin conductance: does it really
measure sudomotor function?
AB - OBJECTIVE: Electrochemical skin conductance (ESC) is a non-invasive test of sweat
function developed as a potential marker of small fiber neuropathy. Here we
systematically review the evolution of this device and the data obtained from
studies of ESC across different diseases. METHODS: Electronic databases,
including MEDLINE, and Google Scholar were searched through to February 2018. The
search strategy included the following terms: "electrochemical skin conductance,"
"EZSCAN," and "Sudoscan." The data values provided by each paper were extracted,
where available, and input into tabular and figure data for direct comparison.
RESULTS: Thirty-seven studies were included this systematic review. ESC did not
change by age or gender, and there was significant variability in ESC values
between diseases, some of which exceeded control values. Longitudinal studies of
disease demonstrated changes in ESC that were not biologically plausible. Of the
37 studies assessed, 25 received support from the device manufacturer. The
extracted data did not agree with other published normative values. Prior studies
do not support claims that ESC is a measure of small fiber sensory function or
autonomic function. CONCLUSIONS: Although many papers report significant
differences in ESC values between disease and control subjects, the compiled data
assessed in this review raises questions about the technique. Many of the
published results violate biologic plausibility. A single funding source with a
vested interest in the study outcomes has supported most of the studies.
Normative values are inconsistent across publications, and large combined data
sets do not support a high sensitivity and specificity. Finally, there is
insufficient evidence supporting the claim that Sudoscan tests sudomotor or
sensory nerve fiber function.
PMID- 29956009
TI - Rescue procedure for left main bronchus obstruction after patent ductus
arteriosus clipping: a case report.
AB - BACKGROUND: Obstruction of the left main bronchus is a rare but life-threatening
complication following the closure of patent ductus arteriosus by surgical clips.
We report a successful rescue procedure for this complication in a premature
infant. CASE PRESENTATION: A 24-week gestational age premature girl weighing 903
g underwent surgical clipping for patent ductus arteriosus at the age of 24 days
after birth. Bronchoscopy revealed the left main bronchus obstruction due to the
clip compression at 6 h later after the surgery. The patient underwent a rescue
re-exploration for this serious complication. New clips were applied to both the
intrapericardial and the aortic ends of the patent ductus arteriosus
respectively. And then the previous clips, compressing the left main bronchus,
were gently removed from the ductus without ductus injury through a re
thoracotomy. CONCLUSIONS: Surgeons should be aware of the possible complication
and take care not to place patent ductus arteriosus clips obliquely toward the
bronchus.
PMID- 29956010
TI - Touch Surgery: a Twenty-First Century Platform for Surgical Training.
AB - This manuscript reviews Touch Surgery, a novel online platform geared towards
innovating professional training for surgical procedures. In other industries,
such as aviation, simulation has already been shown to reduce costs and improve
outcomes in crisis (JETS 3(4):348-352, 2010). Studies involving simulation-based
learning in healthcare similarly indicate the potential for reducing errors
through skill acquisition and cognitive retention (Int J Oral Maxillofac Surg
46:211, 2017). Cohort studies have shown improved performance among simulator
trained medical students in comparison to those with traditional ward training
(Med Teach 9:53-57, 1987). With this front in mind, Touch Surgery is paving its
way for implementation within the surgical realm. The simulations in this
application are numerous and come from over 14 different specialties. This review
details the purpose and features of the application-to include its two distinct
modules-while providing reviews based on its user functionality and application
in medical training. Given the revolutionary shift to simulation-based learning,
platforms like Touch Surgery must now meet the demands of surgical training in
the twenty-first century.
PMID- 29956011
TI - Expression of Gastric Markers Is Associated with Malignant Potential of
Nonampullary Duodenal Adenocarcinoma.
AB - BACKGROUND: Sporadic nonampullary duodenal epithelial tumors (NADETs) are
uncommon, and thus their clinicopathological features have not been fully
assessed. AIMS: In this study, we have analyzed a series of early sporadic
NADETs, focusing on various immunohistological features. METHODS: We conducted a
multicenter retrospective analysis of 68 patients with endoscopically resected
sporadic NADETs. Associations between immunohistological features and
clinicopathological features were statistically analyzed. RESULTS: The 68
patients consisted of 46 men (68%) and 22 women (32%) with a mean age of 60.7 +/-
12.2 years (range 37-85 years). The 68 tumors were composed of 39 adenomas (57%)
and 29 early-stage adenocarcinomas (43%). Duodenal adenocarcinomas were larger in
size than adenomas and had papillary architecture in their pathological diagnosis
with statistical significance. Duodenal adenocarcinomas also demonstrated a
significantly higher expression of gastric markers (MUC5AC and MUC6) and a higher
MIB-1 index. Duodenal adenomas were contrastively apt to express intestinal
markers (MUC2, CDX1 and CDX2). Of the 68 cases analyzed, there were only 3 tumors
positive for p53 staining, all of which were adenocarcinoma. When 7 submucosal
invasive cancers and 21 intramucosal cancers were compared, submucosal invasion
was positively associated with expression of MUC5AC. Also, submucosal invasion
showed strong association with double-positivity of MUC5AC and MUC6. CONCLUSIONS:
Our results indicate that immunohistochemical evaluation is useful for predicting
malignant potential of NADETs, especially focusing on the expression of
gastrointestinal markers.
PMID- 29956012
TI - Improved dissipation kinetic model to estimate permissible pre-harvest residue
levels of pesticides in apples.
AB - Prediction of residual concentrations of applied pesticides during the pre
harvest period may be required to ensure the safety of agricultural products. In
this study, time-dependent dissipation trends of carbaryl (CB), kresoxim-methyl
(KM), flubendiamide (FB), flufenoxuron (FN), bitertanol (BT), and
chlorantraniliprole (CN) applied to apples at recommended and threefold greater
doses were modeled to estimate pre-harvest residue limit concentrations (CPHRL)
indicating permissible pesticide concentrations during the pre-harvest period.
Double-exponential (DE) model results best fit the dissipation trends of all
tested pesticides (correlation coefficients of 0.91-0.99) compared to zero-,
first-, and second-order models. Among the pesticides examined, CB half-lives in
apples of 2.9 and 6.6 days were the shortest, while those of FN (21.1-32.7 days)
were the longest. The CPHRL values for each pesticide in apples were estimated
with DE model parameter values and could be used to determine harvest dates for
safe apples with pesticide concentrations below their maximum residue limits.
Application of the DE model for CPHRL calculation provides more accurate
information for farmers to produce agricultural products safe from pesticide
residues.
PMID- 29956013
TI - Enhanced osteoinductive capacity and decreased variability by enrichment of
demineralized bone matrix with a bone protein extract.
AB - Osteoinductive capacity of demineralized bone matrix (DBM) is sometimes
insufficient or shows high variability between different batches of DBM. Here, we
tried to improve its osteoinductive activity by alkali-urea or trypsin treatment
but this strategy was unsuccessful. Then, we tested the enrichment of DBM with a
bone protein extract (BPE) containing osteogenic growth factors comparing two
sources: cortical bone powder and DBM. The osteoinductive capacity (alkaline
phosphatase activity) of the obtained BPEs was evaluated in vitro in C2C12 cells.
Specific protein levels present in the different BPE was determined by enzyme
linked immunosorbent assay or by a multiplex assay. BPE from cortical bone powder
showed a lack of osteoinductive effect, in agreement with the low content on
osteoinductive factors. In contrast, BPE from DBM showed osteoinductive activity
but also high variability among donors. Thus, we decided to enrich DBM with BPE
obtained from a pool of DBM from different donors. Following this strategy, we
achieved increased osteoinductive activity and lower variability among donors. In
conclusion, the use of a BPE obtained from a pool of demineralized bone to enrich
DBM could be used to increase its osteoinductive effect and normalize the
differences between donors.
PMID- 29956014
TI - A Survey of Data Mining and Deep Learning in Bioinformatics.
AB - The fields of medicine science and health informatics have made great progress
recently and have led to in-depth analytics that is demanded by generation,
collection and accumulation of massive data. Meanwhile, we are entering a new
period where novel technologies are starting to analyze and explore knowledge
from tremendous amount of data, bringing limitless potential for information
growth. One fact that cannot be ignored is that the techniques of machine
learning and deep learning applications play a more significant role in the
success of bioinformatics exploration from biological data point of view, and a
linkage is emphasized and established to bridge these two data analytics
techniques and bioinformatics in both industry and academia. This survey
concentrates on the review of recent researches using data mining and deep
learning approaches for analyzing the specific domain knowledge of
bioinformatics. The authors give a brief but pithy summarization of numerous data
mining algorithms used for preprocessing, classification and clustering as well
as various optimized neural network architectures in deep learning methods, and
their advantages and disadvantages in the practical applications are also
discussed and compared in terms of their industrial usage. It is believed that in
this review paper, valuable insights are provided for those who are dedicated to
start using data analytics methods in bioinformatics.
PMID- 29956015
TI - Impact of five different medial patellofemoral ligament-reconstruction strategies
and three different graft pre-tensioning states on the mean patellofemoral
contact pressure: a biomechanical study on human cadaver knees.
AB - BACKGROUND: The medial patellofemoral ligament (MPFL) is the main stabiliser of
the patella and thus mostly reconstructed in the surgical treatment of
patellofemoral dislocation. The aims of this study were to gain a better
understanding of the influence of altered MPFL graft-fixation locations and
different graft pre-tensions on patellofemoral contact pressure. METHODS: Six
human cadaveric knee joints were placed in a six-degree-of-freedom knee
simulator. Mean PFCP (mPFCP) was evaluated in knee flexion of 0, 30 and 90
degrees using a calibrated pressure-measurement system. After data assessment of
the native knee joint, five MPFL reconstruction conditions were conducted:
Anatomical double bundle; non-anatomical proximal patellar; non-anatomical distal
patellar; non-anatomical proximal femoral; non-anatomical ventral femoral. The
gracilis graft was fixed at a defined knee flexion of 30 degrees and pre
tensioned to 2, 10 and 20 N. RESULTS: Kruskal-Wallis testing resulted in no mPFCP
differences between the native and anatomical reconstruction states. Comparing
the native and anatomical reconstruction states with the non-anatomical
reconstruction states, no difference in the mPFCP both in knee extension (0
degrees ) (p>0.366) and in 30 degrees knee flexion (p>0.349) was found. At 90
degrees knee flexion, the following differences were identified: compared to the
native knee state, the mPFCP increased after non-anatomical proximal femoral and
non-anatomical ventral femoral reconstruction by 257% (p=0.04) and 292%
(p=0.016), respectively. Compared to the anatomical reconstruction state, the
mPFCP increased after non-anatomical proximal femoral reconstruction by 199%
(p=0.042). DISCUSSION AND CONCLUSIONS: With respect to all study findings and to
restore a physiological PFCP, we recommend using the anatomical footprints for
MPFL reconstruction and a moderate graft pretensioning of 2-10 N.
PMID- 29956016
TI - The Parents' Self-Stigma Scale: Development, Factor Analysis, Reliability, and
Validity.
AB - For parents of children with a mental health disorder, self-stigma can negatively
impact their self-esteem and empowerment. Although measures of self-stigma exist,
these have not been created in consultation with parents of children with a
mental health disorder. Thus, the aim of this study was to construct a new scale
based on parents' experiences and developed in partnership with parents through
participatory action research (PAR). Draft items that reflect parents' self
stigmas were drawn from qualitative research. A PAR group further developed these
items for conceptual and experiential representativeness, and wording suitability
and interpretability. With data from 424 parents of children with a mental health
disorder, factor analyses indicated three factors: self-blame, self-shame, and
bad-parent self-beliefs. These factors were negatively correlated with self
esteem and empowerment. Internal consistencies were acceptable. In sum, parent
self-stigma is best operationalised as including self-blame, self-shame, and bad
parent self-beliefs. A valid, PAR-informed measure is provided to promote
consistent, authentic, and sensitive measurement of these components.
PMID- 29956017
TI - Heparin impairs angiogenic signaling and compensatory lung growth after left
pneumonectomy.
AB - Children with hypoplastic lung diseases, such as congenital diaphragmatic hernia,
can require life support via extracorporeal membrane oxygenation and systemic
anticoagulation, usually in the form of heparin. The role of heparin in
angiogenesis and organ growth is inconclusive, with conflicting data reported in
the literature. This study aimed to investigate the effects of heparin on lung
growth in a model of compensatory lung growth (CLG). Compared to the absence of
heparin, treatment with heparin decreased the vascular endothelial growth factor
(VEGF)-mediated activation of VEGFR2 and mitogenic effect on human lung
microvascular endothelial cells in vitro. Compared to non-heparinized controls,
heparinized mice demonstrated impaired pulmonary mechanics, decreased respiratory
volumes and flows, and reduced activity levels after left pneumonectomy. They
also had lower lung volume, pulmonary septal surface area and alveolar density on
morphometric analyses. Lungs of heparinized mice displayed decreased
phosphorylation of VEGFR2 compared to the control group, with consequential
downstream reduction in markers of cellular proliferation and survival. The use
of bivalirudin, an alternative anticoagulant that does not interact with VEGF,
preserved lung growth and pulmonary mechanics. These results demonstrated that
heparin impairs CLG by reducing VEGFR2 activation. These findings raise concern
for the clinical use of heparin in the setting of organ growth or regeneration.
PMID- 29956018
TI - Regulation of angiogenesis by microRNAs in cardiovascular diseases.
AB - Non-coding RNAs are functional RNA molecules comprising the majority of human
transcriptome. Only about 1.5% of the human genome is transcribed into messenger
RNAs (mRNA) that are translated into proteins. Among the non-coding RNAs, miRNAs
are extensively studied and miR targets in endothelial cells, perivascular cells,
and angiogenic signaling are relatively well defined. MicroRNAs not only regulate
transcripts in situ but also function as paracrine mediators in affecting
angiogenesis at distant sites. Exosomal miRs are implicated in modulating
endothelial cell function and angiogenesis. Thus miRs have been shown to affect
tissue microenvironment in a multitude of ways. A comprehensive analysis of the
role of miRs in modulation of angiogenesis and their impact on cardiovascular
diseases is presented in this review.
PMID- 29956019
TI - Sclerostin and parathyroid hormone responses to acute whole-body vibration and
resistance exercise in young women.
AB - Whole-body vibration (WBV) has been shown to improve bone mineral density, and
muscle strength and power. No studies to date have examined sclerostin and
parathyroid hormone (PTH) responses to WBV combined with resistance exercise
(RE). This randomized crossover study compared acute serum sclerostin and PTH
responses to RE and WBV + RE in young women (n = 9) taking oral contraceptives.
Participants were exposed to 5 1-min bouts of vibration (20 Hz, 3.38 peak-peak
displacement, separated by 1 min of rest) before high intensity resistance
exercise. Fasting blood samples were obtained before (PRE), immediately after WBV
(POSTWBV), immediately post RE (IP) and 30 min post RE (30P). Pre-exercise
sclerostin and PTH levels were not significantly different between conditions.
Sclerostin levels significantly (p < 0.05) increased from PRE to IP for the WBV +
RE condition, then decreased back to the pre-exercise level. PTH significantly
decreased from PRE to 30P (p < 0.05) and IP to 30P (p < 0.01) for both
conditions. Correcting for hemoconcentration eliminated the significant
sclerostin responses, but the significant decrease in PTH remained (p < 0.05).
There were no significant relationships found between sclerostin and PTH. In
conclusion, sclerostin concentrations increased in response to the WBV + RE
condition, which may have been mediated by plasma volume shifts. There was no
transient PTH increase, but it showed a large decrease at 30P for both
conditions. Based on these findings, the addition of WBV exposures prior to high
intensity RE did not alter sclerostin and PTH responses to RE in young women.
PMID- 29956020
TI - Incidence of four major types of osteoporotic fragility fractures among elderly
individuals in Sado, Japan, in 2015.
AB - The aim of this study was to survey the incidence of osteoporotic fragility
fractures, which include vertebral, hip, distal radius, and proximal humerus
fractures, in patients >= 50 years of age, from 2004 to 2015, in Sado City,
Japan. We examined temporal changes in the incidence of these fractures from 2010
through 2015. The incidence of vertebral (p < 0.001) and radius fractures (p =
0.001) was lower in 2015 than in 2010, with only the incidence of hip fracture (p
= 0.013) being lower in 2015 than in 2004. With regard to age-specific
incidences, there was a sharp increase in vertebral and hip fractures among the
segment of the population 70-89 years old, with no remarkable change in the
incidence of radial and humeral fractures. Pre-existing vertebral fractures were
identified in 69.6% of patients with a hip fracture, 35.6% of patients with a
distal radius fracture, and 55% of patients with a humeral fracture. Among
patients with pre-existing vertebral fractures, 42.5% had a single fracture,
whereas 57.5% had 2 or more fractures. The proportion of patients on anti
osteoporotic agents before the occurrence of fractures increased to 14.5% in
2015, compared to 4% in 2004 and 7.6% in 2010. We speculate that the increase in
the use of anti-osteoporotic agents is the main reason for the declining
incidence of fractures. Therefore, considering the sharp increase in hip and
vertebral fractures among individuals in their mid-1970s and older, judicious use
of anti-osteoporotic agents among these individuals could be useful for lowering
the occurrence of these fractures.
PMID- 29956021
TI - Factors associated with low trabecular bone scores in patients with end-stage
kidney disease.
AB - The trabecular bone score (TBS) is a textural index that indirectly assesses bone
trabecular microarchitecture using lumbar spine images obtained by dual-energy X
ray absorptiometry (DXA). This study compared the TBS of patients with end-stage
kidney disease (ESKD) with that of matched controls to identify risk factors
associated with a low TBS. TBS and bone mineral density (BMD) were assessed in
ESKD patients (n = 76) and age- and sex-matched control subjects (n = 76) using
DXA. The TBS of both groups was then compared, and risk factors associated with a
low TBS (defined as <= 1.31) were evaluated. The mean TBS in the ESKD group was
significantly lower than that in the control group (1.34 +/- 0.15 vs. 1.43 +/-
0.08, respectively; p < 0.001). More subjects in the ESKD group had a low TBS
[34.2% (ESRD) vs. 5.3% (controls); p < 0.001]. The TBS was negatively correlated
with age, alkaline phosphatase and C-reactive protein levels, and dialysis
vintage, and positively correlated with BMD at the lumbar spine, femoral neck,
and hip. Multivariate analysis identified lower estimated glomerular filtration
rate and increased C-reactive protein levels as being significantly associated
with a low TBS. In conclusion, ESKD patients had abnormal bone microarchitecture
(as assessed by the TBS). The TBS was positively correlated with BMD. Renal
function and inflammatory marker levels were independently associated with a low
TBS. Thus, TBS may be a useful clinical tool for assessing cancellous bone
connectivity in ESKD patients.
PMID- 29956022
TI - Echocardiographic features of PFOs and paradoxical embolism: a complicated
puzzle.
AB - Patent foramen ovale (PFO) is a residual, oblique, slit or tunnel like
communication in the atrial septum that persists into adulthood. It is usually an
incidental finding with no clinical repercussions. Nevertheless, recent evidence
supports the association between the presence of a PFO and a number of clinical
conditions, most notably cryptogenic stroke (CS). There is enough evidence that
paradoxical embolism is a mechanism which can explain this association. Patient
characteristics and certain echocardiography-derived anatomical and hemodynamic
features of PFO provide great assistance in estimating the probability of
paradoxical embolism. In this review, we initially describe PFO embryology and
anatomy. We extensively present the available data on clinical, anatomical and
hemodynamic features of PFOs which have been correlated with increased likelihood
of paradoxical embolism and recent evidence of therapeutic management.
PMID- 29956023
TI - Genetic approach towards a vaccine against malaria.
AB - Malaria is a major concern for international health authorities. Millions of
people contract it every year in the world due to a parasite of the Plasmodium
genus. Due to the complexity of the parasite biology and genetics, there is
currently no vaccine against the disease. However, due to the great resistance
both to the medicines and to the insecticides used to combat the disease, it has
become essential to obtain a vaccine as the necessary tool to prevent
transmission and eliminate the disease. The bibliometric data indicate that
interest in vaccines has been growing steadily since the 1980s. But nowadays, a
powerful tool is used: the Plasmodium genome. This allows us to improve the fight
against the disease. Knowing the sequences of the genes that favor the appearance
of drug resistance, or those that encode for proteins with greater antigenic
response, is a tool that can become fundamental. This article reviews the state
of the art on vaccines and genetics, in the fight against malaria, and analyzes
the fixed photo that the worldwide research on the disease poses.
PMID- 29956024
TI - Extremely and pandrug-resistant bacteria extra-deaths: myth or reality?
AB - In 2009, the European Centre for Disease Prevention and Control (ECDC) estimated
that multidrug-resistant (MDR) bacterial infections were responsible for 25,000
extra-deaths per year. In 2015, another report estimated that 12,500 extra-deaths
were attributable to MDR bacteria every year in France. Recently, the United
Nations claimed that resistance to antimicrobials was a global scourge,
forecasting 10 million deaths in 2050. Surprisingly, our antibiotic resistance
surveillance system in Marseille, France, did not allowed us to observe similar
trends. We herein compared our data on extremely drug-resistant (XDR)/pandrug
resistant (PDR) patient extra-deaths to evaluations and predictions from these
reports. First, we retrospectively collect and analyze antibiotic resistance data
produced by our settings between November 2009 and March 2015 to look for 30-day
deaths attributable to XDR/PDR strains belonging to 11 bacterial species/genus.
In parallel, we performed a PubMed literature search to look for articles
published prior to July 2016 and describing human deaths due to PDR strains.
Overall, 35,723 patients were infected by at least one bacterial species/genus of
interest and 85 by XDR/PDR strains. Of these patients, only one death was
attributable to a XDR bacterial infection in a patient with strong comorbidities
and two consecutive septic shocks. Our literature review shows that only four
articles described human deaths due to PDR bacteria. All together, these data
allowed us to conclude that there is a large discrepancy between the real count
of deaths attributable to XDR/PDR bacteria and alarmist predictions.
PMID- 29956026
TI - Multiple clinical features of Huntington's disease correlate with mutant HTT gene
CAG repeat lengths and neurodegeneration.
AB - Huntington's disease (HD) is a fatal neurodegenerative disease caused by mutant
HTT gene expansions of CAG triplet repeat numbers that are inherited in an
autosomal dominant manner. HD patients display multiple clinical features that
are correlated with HTT CAG repeat numbers that include age of disease onset,
motor dysfunction, cognitive deficits, compromised daily living capacity, and
brain neurodegeneration. It is important to understand the significant
relationships of the multiple HD clinical deficits correlated with the number of
mutant HTT CAG expansions that are the genetic basis for HD disabilities.
Therefore, this review highlights the significant correlations of the HD clinical
features of age of onset, motor and cognitive disabilities, decline in living
capabilities, weight loss, risk of death, and brain neurodegeneration with
respect to their associations with CAG repeat lengths of the HTT gene.
Quantitative HTT gene expression patterns analyzed in normal adult human brain
regions demonstrated its distribution in areas known to undergo neurodegeneration
in HD, as well as in other brain regions. Future investigation of the
relationships of the spectrum of clinical HD features with mutant HTT molecular
mechanisms will be important to gain understanding of how mutant CAG expansions
of the HTT gene result in the devastating disabilities of HD patients.
PMID- 29956025
TI - The effects of anodal tDCS over the supplementary motor area on gait initiation
in Parkinson's disease with freezing of gait: a pilot study.
AB - OBJECTIVE: We investigated if anodal transcranial direct current stimulation (A
tDCS), applied over the supplementary motor areas (SMAs), could improve gait
initiation in Parkinson's disease (PD) with freezing of gait (FOG). METHODS: In
this double-blinded cross-over pilot study, ten PD with FOG underwent two
stimulation sessions: A-tDCS (1 mA, 10 min) and sham stimulation. Eight blocks of
gait initiation were collected per session: (1) pre-tDCS, with acoustic cueing;
(2) pre-tDCS, self-initiated (no cue); and (3-8) post-tDCS, self-initiated. Gait
initiation kinetics were analyzed with two-way repeated measures ANOVAs for the
effects of A-tDCS. RESULTS: A-tDCS did not significantly improve the magnitude or
timing of anticipatory postural adjustments or the execution of the first step
during self-initiated gait compared with baseline measures (p > .13). The lack of
significant change was not due to an inability to generate functional APAs since
external cueing markedly improved gait initiation (p < .01). CONCLUSIONS: A
single dose of A-tDCS over the SMAs did not improve self-initiated gait in PD and
FOG. Alternative approaches using a different dose or cortical target are worthy
of exploration since individuals demonstrated the capacity to improve.
SIGNIFICANCE: Neuromodulation strategies tailored to facilitate SMA activity may
be ineffective for the treatment of gait initiation impairment in people with PD
and FOG.
PMID- 29956027
TI - Prospective study of relevance of 123I-MIBG myocardial scintigraphy and clonidine
GH test to distinguish Parkinson's disease and multiple system atrophy.
AB - BACKGROUND: 123I-MIBG myocardial scintigraphy and clonidine growth hormone test
(CGH test) may help to distinguish multiple system atrophy (MSA) from Parkinson's
disease (PD). Their relevance in the first-stage parkinsonism of uncertain
etiology is unknown. METHODS: Patients experiencing parkinsonism of ambiguous
etiology were clinically classified into the PD group or the MSA group as initial
clinical diagnosis (ICD). Then, CGH test and myocardial scintigraphy were
performed. Clinical assessment was repeated throughout the disease course until
the final clinical diagnosis (FCD) could be established according to the criteria
of PD and MSA, respectively. RESULTS: Twenty-five patients with uncertain
diagnosis were included (15 MSA and 10 PD as ICD). At the end of a 6-year follow
up, FCD was MSA in 11/25 patients and PD in 14/25. The CGH test and the
scintigraphy showed a sensitivity of 82%, and a specificity of 71 and 93%,
respectively, for the diagnosis of MSA. The combination of a normal scintigraphy
(i.e., with myocardial MIBG uptake) with genitourinary dysfunction was the most
relevant test to diagnose MSA, whereas an abnormal scintigraphy with a levodopa
response of > 30% or an abnormal scintigraphy with the absence of OH was the most
relevant combinations to diagnose PD. All these combinations had an accuracy
superior than 90% and a specificity of 100%. CONCLUSION: Combinations of
myocardial scintigraphy with genitourinary dysfunction, levodopa response of >
30%, or orthostatic hypotension could be of interest for the distinction between
PD and MSA when the clinical diagnosis remains ambiguous at the first stage of
the disease.
PMID- 29956029
TI - Utilisation of an operative difficulty grading scale for laparoscopic
cholecystectomy.
AB - BACKGROUND: A reliable system for grading operative difficulty of laparoscopic
cholecystectomy would standardise description of findings and reporting of
outcomes. The aim of this study was to validate a difficulty grading system
(Nassar scale), testing its applicability and consistency in two large
prospective datasets. METHODS: Patient and disease-related variables and 30-day
outcomes were identified in two prospective cholecystectomy databases: the multi
centre prospective cohort of 8820 patients from the recent CholeS Study and the
single-surgeon series containing 4089 patients. Operative data and patient
outcomes were correlated with Nassar operative difficultly scale, using Kendall's
tau for dichotomous variables, or Jonckheere-Terpstra tests for continuous
variables. A ROC curve analysis was performed, to quantify the predictive
accuracy of the scale for each outcome, with continuous outcomes dichotomised,
prior to analysis. RESULTS: A higher operative difficulty grade was consistently
associated with worse outcomes for the patients in both the reference and CholeS
cohorts. The median length of stay increased from 0 to 4 days, and the 30-day
complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to
4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found
to be most strongly associated with conversion to open and 30-day mortality
(AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar
operative difficultly scale was found to be a significant independent predictor
of operative duration, conversion to open surgery, 30-day complications and 30
day reintervention (all p < 0.001). CONCLUSION: We have shown that an operative
difficulty scale can standardise the description of operative findings by
multiple grades of surgeons to facilitate audit, training assessment and
research. It provides a tool for reporting operative findings, disease severity
and technical difficulty and can be utilised in future research to reliably
compare outcomes according to case mix and intra-operative difficulty.
PMID- 29956028
TI - Robotic-assisted versus laparoscopic cholecystectomy for benign gallbladder
diseases: a systematic review and meta-analysis.
AB - BACKGROUND: Robotic surgery, an emerging technology, has some potential
advantages in many complicated endoscopic procedures compared with laparoscopic
surgery. But robot-assisted cholecystectomy (RAC) is still a controversial issue
on its comparative merit compared with conventional laparoscopic cholecystectomy
(LC). The aim of this study was to evaluate the safety and efficacy of RAC
compared with LC for benign gallbladder disease. METHODS: A systematic literature
search was conducted using the PubMed, EMBASE, and Cochrane Library databases
(from their inception to December 2017) to obtain comparative studies assessing
the safety and efficacy between RAC and LC. The quality of the literature was
assessed, and the data analyzed using R software, random effects models were
applied. RESULTS: Twenty-six studies, including 5 RCTs and 21 NRCSs (3
prospective plus 18 retrospective), were included. A total of 4004 patients were
included, of which 1833 patients (46%) underwent RAC and 2171 patients (54%)
underwent LC. No significant differences were found in intraoperative
complications, postoperative complications, readmission rate, hospital stay,
estimated blood loss, and conversion rate between RAC and LC groups. However, RAC
was related to longer operative time compared with LC (MD = 12.04 min, 95% CI
7.26-16.82) in RCT group, which was consistent with NRCS group; RAC also had a
higher rate of incisional hernia in NRCS group (RR = 3.06, 95% CI 1.42-6.57), and
one RCT reported that RAC was similar to LC (RR = 7.00, 95% CI 0.38-129.84).
CONCLUSIONS: The RAC was not found to be more effective or safer than LC for
benign gallbladder diseases, which indicated that RAC is a developing procedure
instead of replacing LC at once. Given the higher costs, the current evidence is
in favor of LC in cholecystectomy.
PMID- 29956030
TI - Perioperative outcomes of laparoscopic pancreaticoduodenectomy for benign and
borderline malignant periampullary disease compared to open
pancreaticoduodenectomy.
AB - PURPOSE: The objective of this study was to compare perioperative outcomes
between laparoscopic pancreaticoduodenectomy (LPD) and open
pancreaticoduodenectomy (OPD) for benign and borderline malignant periampullary
diseases. METHODS: Of 107 pancreaticoduodenectomy cases for non-malignant
diseases from March 1993 to July 2017, 76 patients underwent OPD and 31 patients
received LPD. To adjust for baseline differences and selection bias, operative
outcomes and complications were compared after propensity score matching (PSM).
RESULTS: After 1:1 PSM, well-matched 31 patients in each group were evaluated. As
a result, significant differences were observed between two groups in some
aspects: mean operative time (LPD 426.8 +/- 98.58 vs. OPD 355.03 +/- 100.0 min, p
= 0.031), estimated blood loss (LPD 477.42 +/- 374.80 vs. OPD 800.00 +/- 531.35
ml, p = 0.008), and postoperative hospital stay (LPD 14.74 +/- 5.40 vs. OPD 23.81
+/- 11.63 days, p < 0.001). The average visual analogue scores for pain observed
from patients in LPD group on postoperative day (POD) 1 (4.23 +/- 1.83 vs. 5.55
+/- 2.50, p = 0.021) and POD 3 (3.32 +/- 1.66 vs. 5.26 +/- 2.76, p = 0.002) were
significantly less than those from patients in OPD group, as well. There were no
significant differences between groups about major complications including the
rate of postoperative pancreatic fistula. CONCLUSIONS: LPD is a safe procedure
and provides less postoperative pain and the shortening length of
hospitalization. LPD may serve the feasible alternative approach for benign and
borderline malignant periampullary disease.
PMID- 29956031
TI - Ischemic gastropathy after distal pancreatectomy with en bloc celiac axis
resection for pancreatic body cancer.
AB - PURPOSE: Risk factors of ischemic gastropathy (IG) following distal
pancreatectomy with en bloc celiac axis resection (DP-CAR) remain unclear.
METHODS: Fifty consecutive patients with pancreatic cancer who underwent DP-CAR
were retrospectively reviewed for possible risk factors for IG. This study was
registered on the UMIN Clinical Trials Registry (UMIN 000028732). RESULTS:
Complications higher than grade 3 were observed in 21 patients (42%) and
mortality in 4 (8%). Left gastric artery (LGA) resection (P = 0.046) and a
combination of left inferior phrenic artery (IPA) with LGA resection (P = 0.012)
were risk factors of IG, and an elevated creatine kinase (CK) value >= 1005 IU/L
(P = 0.025) was associated with IG. Among prognostic factors, IG (OR, 5.997; 95%
CI, 1.543-23.309; P = 0.010), completion of adjuvant chemotherapy (OR, 0.282; 95%
CI, 0.121-0.654; P = 0.003), longer operative time (OR, 2.261; 95% CI, 1.084
4.714; P = 0.030), and higher age (OR, 2.212; 95% CI, 1.081-4.524; P = 0.030)
remained independent predictors of survival. Comparison at 2 and 3 months
postoperatively showed nutritional values were higher in patients who underwent
LGA-preserving DP-CAR than those with LGA-resecting DP-CAR: total protein (7.17
+/- 0.56 vs 6.65 +/- 0.66 g/dl, P = 0.007), albumin (4.04 +/- 0.45 vs 3.43 +/-
0.43 g/dl, P < 0.001), and total cholesterol (162.3 +/- 34.7 vs 141.6 +/- 27.2
mg/dl, P = 0.044). CONCLUSIONS: The poorer prognosis in patients who undergo DP
CAR may be related to more advanced tumors. A combination of left IPA and LGA
resection was a significant risk factor for IG. IG, completion of adjuvant
chemotherapy, longer operative time, and higher age remain good independent
predictors of survival.
PMID- 29956032
TI - Segment 5 parenchymal sparing in extended left hepatectomy with respect to venous
outflow-is it a feasible procedure?
AB - BACKGROUND: Segment 5 (S5) sparing liver resection for cases that require an
anatomic left trisectionectomy has not been reported yet. The authors intended to
verify the outcome of S5-sparing extended left hepatectomy (ELH) in respect to
venous outflow. METHODS: All adult patients who underwent S5-sparing ELH between
2012 and 2017 in authors' institute have been enrolled in this study. S5-sparring
ELH was defined as resection of S2, S3, S4, and S8 with or without S1. The
surgery planning was based on the images from two-dimensional triphasic computed
tomography and/or magnetic resonance imaging. A three-dimensional image
reconstruction and liver volumetric study were performed retrospectively.
RESULTS: Out of 177 cases of major hepatic resection, only seven non-hilar
cholangiocarcinoma patients underwent ELH during the study period. S5-sparing ELH
was performed to five patients, in whom no tumor involvement in S5. The venous
outflow of S5 has been maintained intraoperative, and S5 congestion has not been
observed in all patients. Tailored management of the S5 venous outflow ensured an
increase in functional remnant liver volume by 52.8% (range, 25.6 to 66.9%) by
sparing of S5. A negative resection margin was achieved in all patients. One
patient had postoperative bile leak requiring reoperation. No posthepatectomy
liver failure (PHLF) has been observed. CONCLUSION: S5-sparing ELH is technically
feasible. Under the tailored management of S5 venous outflow, the functional
future liver remnant can be increased. Further studies with larger sample size
are needed to evaluate which circumstances the liver segment 5 could be preserved
without venous reconstruction during the left extended hepatectomy.
PMID- 29956033
TI - A Review on the Electrochemically Self-organized Titania Nanotube Arrays:
Synthesis, Modifications, and Biomedical Applications.
AB - Titania nanotubes grown by anodic oxidation have intrigued the material science
community by its many unique and potential properties, and the synthesis of
technology is merging to its mature stage. The present review will focus on TiO2
nanotubes grown by self-organized electrochemical anodization from Ti metal
substrate, which critically highlights the synthesis of this type of self
organized titania nanotube layers and the means to influence the size, shape, the
degree of order, and crystallized phases via adjusting the anodization parameters
and the subsequent thermal annealing. The relationship between dimensions and
properties of the anodic TiO2 nanotube arrays will be presented. The latest
progress and significance of the research on formation mechanism of anodic TiO2
nanotubes are briefly discussed. Besides, we will show the most promising
applications reported recently in biomedical directions and modifications carried
out by doping, surface modification, and thermal annealing toward improving the
properties of anodically formed TiO2 nanotubes. At last, some unsolved issues and
possible future directions of this field are indicated.
PMID- 29956034
TI - Combined habit reversal training and exposure response prevention in a group
setting compared to individual training: a randomized controlled clinical trial.
AB - Chronic tic disorders may have a huge influence on quality of life. Habit
reversal training (HRT) and exposure response prevention (ERP) are effective
treatments. In a blinded assessed, open trial, this study evaluates the
effectiveness of a newly developed Scandinavian tic treating manual designed to
treat adolescents with a chronic tic disorder, combining HRT and ERP. The study
compared the efficacy of treatment based on the same manual delivered either
individually or in groups. The study was an open randomized controlled clinical
trial in which adolescents were randomized to either individual or group therapy.
Both therapies included nine sessions. The parents were offered group-based
psycho-education. The exclusion criteria were chosen to design a study that would
be close to clinical practice. This is the first Scandinavian study that examines
the effectiveness of a treatment manual combining HRT and ERP delivered in an
individual and group setting. The study showed a significant reduction of the
Total Tic score on the Yale Global Tic Severity Scale both in the individual
(effect size 1.21) and group setting (effect size 1.38). A total of 66.7% of
participants were considered responders. There was no statistical significant
difference between the individual and group setting apart from the functional
impairment score. The reductions were comparable with those shown in other
studies. The participants applied both HRT and ERP, and the majority (36/59)
reported an increased post-treatment experience of control. The newly designed
Scandinavian manual was equally effective in the individual and group setting
with effect sizes comparable with those shown in other studies.
PMID- 29956035
TI - Cluster analysis describes constellations of cardiac anomalies presenting in
spinal anomaly patients.
AB - BACKGROUND: Cardiac anomalies are prevalent in patients with bony spinal
anomalies. Prior studies evaluating incidences of bony congenital anomalies of
the spine are limited. The Kids' Inpatient Database (KID) yields national
discharge estimates of rare pediatric conditions like congenital disorders. This
study utilized cluster analysis to study patterns of concurrent vertebral
anomalies, anal atresia, cardiac malformations, trachea-esophageal fistula, renal
dysplasia, and limb anomalies (VACTERL anomalies) co-occurring in patients with
spinal congenital anomalies. METHODS: Retrospective review of KID 2003-2012. KID
supplied hospital- and year-adjusted weights allowed for incidence assessment of
bony spinal anomalies and cardiac, gastrointestinal, urinary anomalies of
VACTERL. K-means clustering assessed relationships between most frequent
anomalies within bony spinal anomaly discharges; k set to n - 1(n = first
incidence of significant drop/little gain in sum of square errors within
clusters). RESULTS: There were 12,039,432 KID patients 0-20 years. Incidence per
100,000 discharges: 2.5 congenital fusion of spine, 10.4 hemivertebra, 7.0
missing vertebra. The most common anomalies co-occurring with bony vertebral
malformations were atrial septal defect (ASD 12.3%), large intestinal atresia
(LIA 11.8%), and patent ductus arteriosus (PDA 10.4%). Top congenital cardiac
anomalies in vertebral anomaly patients were ASD, PDA, and ventricular septal
defect (VSD); all three anomalies co-occur at 6.6% rate in this vertebral anomaly
population. Cluster analysis revealed that of bony anomaly discharges, 55.9% of
those with PDA had ASD, 34.2% with VSD had PDA, 22.9% with LIA had ASD, 37.2%
with ureter obstruction had LIA, and 35.5% with renal dysplasia had LIA.
CONCLUSIONS: In vertebral anomaly patients, the most common co-occurring
congenital anomalies were cardiac, renal, and gastrointestinal. Top congenital
cardiac anomalies in vertebral anomaly patients were ASD, PDA, and VSD. VACTERL
patients with vertebral anomalies commonly presented alongside cardiac and renal
anomalies.
PMID- 29956037
TI - Abstracts of the Total Body PET conference 2018 : Ghent, Belgium. 30 June - 2
July 2018.
PMID- 29956036
TI - Morin Attenuates Neurochemical Changes and Increased Oxidative/Nitrergic Stress
in Brains of Mice Exposed to Ketamine: Prevention and Reversal of Schizophrenia
Like Symptoms.
AB - Previous studies have revealed that morin (MOR), a neuroactive bioflavonoid, with
proven psychotropic and neuroprotective properties reduced schizophrenic-like
behaviors in mice. This study further evaluated the ability of MOR to prevent and
reverse ketamine-induced schizophrenic-like behaviors and the underlying
neurochemical changes and increased oxidative/nitrergic stress in mice. In the
preventive protocol, mice received intraperitoneal injection of MOR (100 mg/kg),
reference antipsychotic drugs [haloperidol (1 mg/kg), risperidone (0.5 mg/kg)],
or saline daily for 14 consecutive days prior to i.p. injection of ketamine (KET)
(20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the
animals received KET or saline for 14 days prior to MOR, haloperidol,
risperidone, or saline treatments. Schizophrenic-like behaviors: positive (open
field test), negative (social-interaction test) and cognitive (Y-maze test)
symptoms were evaluated. Thereafter, the brain levels of dopamine, glutamate, 5
hydroxytryptamine and acetyl-cholinesterase, as well as biomarkers of
oxidative/nitrergic stress were measured in the striatum, prefrontal-cortex (PFC)
and hippocampus (HC). Morin prevented and reversed KET-induced hyperlocomotion,
social and cognitive deficits. Also, MOR or risperidone attenuated altered
dopaminergic, glutamatergic, 5-hydroxytryptaminergic and cholinergic
neurotransmissions in brain region-dependent manner. The increased
malondialdehyde and nitrite levels accompanied by decreased glutathione
concentrations in the striatum, PFC and HC in KET-treated mice were significantly
attenuated by MOR or risperidone. Taken together, these findings suggest that the
anti-schizophrenic-like activity of MOR may be mediated via mechanisms related to
attenuation of neurochemical changes and oxidative/nitrergic alterations in mice.
PMID- 29956038
TI - 4-Amino-2,3-dihydro-1lambda6-isothiazole-1,1-dioxides and their chemical
properties evaluation.
AB - The reactivity of the 4-amino-2,3-dihydro-1H-1lambda6-isothiazole-1,1-dioxide
(beta-amino-gamma-sultam) framework has not been studied sufficiently. Here we
describe the chemical properties of this heterocyclic system toward electrophiles
on spiranic and non-spiranic substrates. A variety of C-electrophiles (acetic
anhydride, benzoyl chloride, DMFDMA, 4,4-dimethoxybutan-2-one) and heteroatom
electrophiles (bromine, nitrosyl acetate) have been explored. Both the C-5 and 4
amino positions of the beta-amino-gamma-sultam system are able to undergo
electrophilic reactions. Heteroatom electrophiles attack the C-5 position,
whereas carbo-electrophiles affect the amino group. beta-Amino-gamma-sultams also
were used as starting compounds for the synthesis of 6- or 7-substituted 1lambda6
isothiazolo[4,5-b]pyridine-1,1-dioxides through condensation reaction and
palladium-catalyzed oxidative coupling.
PMID- 29956040
TI - Mass spectrometric characterization of siderophores produced by Pseudomonas
taiwanensis VLB120 assisted by stable isotope labeling of nitrogen source.
AB - The structures of three previously unknown siderophores produced by the
fluorescent, biotechnologically relevant Pseudomonas taiwanensis (P. taiwanensis)
VLB120 bacteria were elucidated by means of hydrophilic interaction liquid
chromatography (HILIC) hyphenated to high-resolution tandem mass spectrometry
(HRMS/MS). They could be verified as iron(III)- and aluminum(III) complexes as
well as the protonated molecules of the siderophores formed by in-source
fragmentation. The siderophores were separated according to their different acyl
side chains and additionally according their central ions. One of the
siderophores was identified as pyoverdine with a malic acid (hydroxy succinic
acid) amide side chain and a peptide moiety consisting of Orn-Asp-OHAsn-Thr
AcOHOrn-Ser-cOHOrn. The other analytes were assigned to an azotobactin with the
identical peptide chain linked to the characteristic chromophoric unit and a
pyoverdine with a variation in the amino acid sequence. Proline is directly
linked to the pyoverdine chromophore instead of ornithine. Acidic and enzymatic
hydrolyses were carried out to analyze the individual amino acids. Beside OHAsn,
each amino acid of the peptide part was identified by HILIC-HRMS and comparison
to authentic standards. Additionally, 15N-labeled cellular supernatants were
analyzed by means of HRMS/MS. The results of the MS/MS experiments complemented
by accurate mass data facilitated elucidation of the structures studied in this
work and provided further confirmation of the three recently described
pyoverdines of P. taiwanensis VLB120 (Baune et al. in Biometals 30:589-597, 2017.
https://doi.org/10.1007/s10534-017-0029-7 ).
PMID- 29956039
TI - Molecular mechanism of SRP-dependent light-harvesting protein transport to the
thylakoid membrane in plants.
AB - The light-harvesting chlorophyll a/b binding proteins (LHCP) belong to a large
family of membrane proteins. They form the antenna complexes of photosystem I and
II and function in light absorption and transfer of the excitation energy to the
photosystems. As nuclear-encoded proteins, the LHCPs are imported into the
chloroplast and further targeted to their final destination-the thylakoid
membrane. Due to their hydrophobicity, the formation of the so-called 'transit
complex' in the stroma is important to prevent their aggregation in this aqueous
environment. The posttranslational LHCP targeting mechanism is well regulated
through the interaction of various soluble and membrane-associated protein
components and includes several steps: the binding of the LHCP to the
heterodimeric cpSRP43/cpSRP54 complex to form the soluble transit complex; the
docking of the transit complex to the SRP receptor cpFtsY and the Alb3
translocase at the membrane followed by the release and integration of the LHCP
into the thylakoid membrane in a GTP-dependent manner. This review summarizes the
molecular mechanisms and dynamics behind the posttranslational LHCP targeting to
the thylakoid membrane of Arabidopsis thaliana.
PMID- 29956041
TI - Utilizing the Quantitative Electroencephalograph (qEEG) to Objectively Document
the Nature and Severity of Concussions in Junior Hockey Players: A Pilot
Investigation.
AB - Concussions represent a major concern for hockey teams. During one winter season,
all players on two Junior Hockey Teams were assessed in order to establish an
incidence baseline for concussions. The qEEG was utilized as it measures the
probability of concussion and its severity. The SCL 90-R and CNS questionnaire
were used to provide insight into various aspects of cognitive functioning.
Results indicated that of the players assessed (N = 46) approximately two-thirds
(N = 32) tested positive for concussions. A minority of the concussions were
assessed as mild (N = 13), while 19 were assessed as moderately severe. The most
common sites indicated as injured were F8 and T6 (right side of head) and O1 and
O2 (back of head) and F7 (left front of head). A comparison of the questionnaire
results to expected behavioural issues are discussed. This appears to be one of
the first studies of junior hockey players using an objective measure of study
(qEEG).
PMID- 29956043
TI - Correction to: Transition from tube feeding to oral feeding: experience in a
tertiary care paediatric cardiology unit.
AB - The original version of this article inadvertently used early drafts of Figs. 1
and 2. The correct figures are shown here. The original article has been
corrected.
PMID- 29956042
TI - Improvement in Left Ventricular Function with Intracoronary Mesenchymal Stem Cell
Therapy in a Patient with Anterior Wall ST-Segment Elevation Myocardial
Infarction.
AB - BACKGROUND/AIMS: The progression and development of congestive heart failure is
still considered a large problem despite the existence of revascularization
therapies and optimal, state-of-the-art medical services. An acute myocardial
infarction (AMI) is a major cause of congestive heart failure, so researchers are
investigating techniques to complement primary percutaneous coronary intervention
(PCI) or thrombolytic therapy to prevent congestive heart failure after AMI.
METHODS: Twenty-six patients with successful PCI for acute ST-segment elevation
anterior wall myocardial infarction were assigned to either a control group (n =
12) or a bone marrow mesenchymal stem cells (BM-MSC) group (n = 14). The control
group received optimum post-infarction treatment, and the BMSC group received
intracoronary delivery of autologous BMSC at 1 month after PCI with the optimum
medical treatment. The primary endpoint was a left ventricular ejection fraction
(LVEF) change from baseline to 4-month follow-up, as determined via myocardial
single-photon emission computed tomography (SPECT). RESULTS: The global LVEF at
baseline (determined 3.5 +/- 1.5 days after PCI) was 35.4 +/- 3.0% in the control
group and 33.6 +/- 4.7% in the BM-MSC group. BMSC transfer enhanced left
ventricular systolic function primarily in anterior wall myocardial segments
adjacent to the LAD infarcted area. Four months later, via SPECT, global LVEF had
increased by 4.8 +/- 1.9% in the control group and 8.8 +/- 2.9% in the BM-MSC
group (p = 0.031). The cell transfer did not increase the risk of adverse
clinical events, in-stent restenosis, or proarrhythmic effects. The
echocardiographic evaluation also revealed a significant increase in the LVEF
value from baseline to the 4-month (9.0 +/- 4.7 and 5.3 +/- 2.6%, p = 0.023) and
12-month (9.9 +/- 5.2% and 6.5 +/- 2.7%, p = 0.048) follow-up in the BM-MSC group
but not in the control group. CONCLUSIONS: Intracoronary administration of
autologous BM-MSC was tolerable and safe with significant improvement in LVEF at
4-month (SPECT and echocardiography result) and 12-month (echocardiography result
only) follow-up in patients with anterior AMI.
PMID- 29956044
TI - Biosynthesis of D-lactic acid from lignocellulosic biomass.
AB - D-lactic acid is a versatile and important industrial chemical that can be
applied in the synthesis of thermal-resistant poly-lactic acid. Biosynthesis of D
lactic acid can be achieved by a variety of microorganisms, including lactic acid
bacteria, yeast, and fungi; however, the final product yield, optical purity, and
the utilization of both glucose and xylose are restricted. Consequently,
engineered microbial systems are essential to attain high titer, productivity,
and complete utilization of sugars. Herein, we critically evaluate the promising
wild-type microorganisms, as well as genetically modified microorganisms to
produce enantiomerically pure D-lactic acid, particularly from renewable
lignocellulosic biomass. In addition, innovative bioreactor operation, metabolic
flux analysis, and recent genetic engineering methods for targeted microbial D
lactic acid synthesis will be discussed.
PMID- 29956045
TI - Effects of Ethnic Identity on the Relationship Between Mental Health and
Perceived Discrimination Among Ethnic Return Migrants: The Case of Korean Chinese
Return-Migrated to South Korea.
AB - This study examined the relationship among mental health, perceived
discrimination and ethnic identity among Korean Chinese (Joseonjok) who have
return-migrated to South Korea. A survey was conducted with 399 Joseonjok adults
(>= 19 years) residing in the capital city Seoul or nearby. Depression was
measured using the (self-report) Center for Epidemiologic Studies Depression
Scale-Korean (CES-D-K) version (n = 292, mean age = 42.6, female = 56.5%).
Perceived discrimination and ethnic identity were assessed with single-item
questions. The mean CES-D-K total score was 9.3 (SD = 8.4) and 20.6% had clinical
depression (cut-off score: 16). Perceived discrimination was positively
associated with CES-D-K scores (regression coefficient = 2.09, p = 0.04). This
association was stronger in those identifying themselves more strongly as
'Korean' than 'Chinese'. Discrimination by 'co-ethnic hosts' can have a greater
impact on mental health among those ethnic return migrants with a stronger ethnic
identity. More efforts are needed to help them better integrate into South Korean
society.
PMID- 29956046
TI - Olfactory Sensory Neurons of the Asian Longhorned Beetle, Anoplophora
glabripennis, Specifically Responsive to its two Aggregation-Sex Pheromone
Components.
AB - We performed single-sensillum recordings from male and female antennae of the
Asian longhorned beetle, Anoplophora glabripennis, that included as stimuli the
two components of this species' aggregation-sex pheromone in addition to various
general odorants. We compared the aggregation-sex-pheromone-component responses
of olfactory sensory neurons (OSNs) to those of OSNs that responded to a variety
of plant-related odorants. In the smooth-tipped, tapered, trichoid sensilla on
the most distal antennal flagellomeres nos. 10 or 11 of both males and females,
we found OSNs with high-amplitude action potentials that were tuned to the
aldehyde and alcohol pheromone components and that did not respond to various
plant-related volatiles. Because this OSN type responded to both the alcohol and
aldehyde components it cannot be considered to be specifically tuned to either
component. These large-spiking OSNs were co-compartmentalized in these sensilla
with a second, smaller-spiking OSN responding to plant-related volatiles such as
geraniol, citronellal, limonene, 1-octanol, nerol and citral. The large-spiking
OSNs thus appear to be a type that will be involved in aggregation-sex pheromone
pathways targeting a specific glomerulus in the antennal lobe and in generating
pheromone-related behavioral responses in A. glabripennis. In other sensilla
located in these distal antennal flagellomeres as well as those located more
proximally, i.e., mid-length along the antenna on flagellomere nos. 4-7, we found
OSNs in blunt-tipped basiconic sensilla that were responsive to other plant
related volatiles, especially the terpenoids, (E,E)-alpha farnesene, (E)-beta
farnesene, beta-caryophyllene, and eugenol. Some of these terpenoids have been
implicated in improving attraction to pheromone-baited traps. Some of these same
OSNs responded additionally to either of the two sex pheromone components, but
because these OSNs also responded to some of the above plant volatiles as shown
by cross-adaptation experiments, these OSNs will not be the types that convey sex
pheromone-specific information to the antennal lobe.
PMID- 29956048
TI - A risk score to predict postoperative complications after lobectomy in elderly
lung cancer patients.
AB - OBJECTIVE: In elderly patients with lung cancer, the presumed fear of
postoperative complications has resulted in the delivery of limited resection.
Surgical decision-making for such patients would become easier if clinicians
could predict who is at high risk of postoperative complications. The purpose of
this study is to propose a scoring system to predict the risk of postoperative
complications for elderly patients with lung cancer. METHODS: We reviewed
patients aged 75 years or older who underwent lobectomy for lung cancer at a
single hospital (n = 199). A multivariable logistic regression model was utilized
to determine risk factors for postoperative complications. RESULTS: Six risk
factors for postoperative complications were identified, and we derived a risk
score by assigning weights to these factors based on their odds ratios, as
follows: Risk score = 7 * (performance status of 2) + 6 * (coronary artery
disease) + 3 * (a history of cerebrovascular accident) + 2 * (restrictive
ventilatory impairment) + 1 * (male sex) + 1 * (interstitial pneumonia). The
postoperative complication rates in patients with risk scores of 0, 1-2, 3-5, 6
8, and 9-14 were 19, 29, 56, 68, and 90%, respectively. CONCLUSIONS: The proposed
risk score was able to predict the incidence of postoperative complications. The
risk score can be used to identify high-risk patients and to select proper
treatment strategies.
PMID- 29956047
TI - An overview of inborn errors of metabolism manifesting with primary adrenal
insufficiency.
AB - Primary adrenal insufficiency (PAI) results from an inability to produce adequate
amounts of steroid hormones from the adrenal cortex. The most common causes of
PAI are autoimmune adrenalitis (Addison's disease), infectious diseases,
adrenalectomy, neoplasia, medications, and various rare genetic syndromes and
inborn errors of metabolism that typically present in childhood although late
onset presentations are becoming increasingly recognized. The prevalence of PAI
in Western countries is approximately 140 cases per million, with an incidence of
4 per 1,000,000 per year. Several pitfalls in the genetic diagnosis of patients
with PAI exist. In this review, we provide an in-depth discussion and overview on
the inborn errors of metabolism manifesting with PAI, including genetic
diagnosis, genotype-phenotype relationships and counseling of patients and their
families with a focus on various enzymatic deficiencies of steroidogenesis.
PMID- 29956050
TI - CT findings of fungal pneumonia with emphasis on aspergillosis.
AB - Fungal pneumonias are increasingly common in the population of immunosuppressed
patients. The diagnosis of fungal pneumonias represents a challenge for
clinicians, and the morbidity and mortality of these infections are high in
immunocompromised patients. CT findings may be nonspecific; however, in the
appropriate clinical setting, they may suggest and even help establish the
specific diagnosis. This article provides an overview about the CT findings and
possible differential diagnosis of the most common pulmonary fungal infections.
PMID- 29956049
TI - Morphometrical and biomechanical analyses of a stentless bioprosthetic valve: an
implication to avoid potential primary tissue failure.
AB - OBJECTIVES: Stentless bioprosthetic valves provide hemodynamic advantages over
stented valves as well as excellent durability. However, some primary tissue
failures in bioprostheses have been reported. This study was conducted to
evaluate the morphometrical and biomechanical properties of the stentless
Medtronic FreestyleTM aortic root bioprosthesis, to identify any arising problem
areas, and to speculate on a potential solution. METHODS: The three-dimensional
heterogeneity of the stentless bioprosthesis wall was investigated using computed
tomography. The ascending aorta and the right, left, and non-coronary sinuses of
Valsalva were resected and examined by an indentation test to evaluate their
biomechanical properties. RESULTS: The non-coronary sinus of Valsalva was
significantly thinner than the right sinus of Valsalva (p < 0.01). Young's
modulus, calculated as an indicator of elasticity, was significantly greater at
the non-coronary sinus of Valsalva (430.7 +/- 374.2 kPa) than at either the left
(190.6 +/- 70.6 kPa, p < 0.01) or right sinuses of Valsalva (240.0 +/- 56.5 kPa,
p < 0.05). CONCLUSIONS: Based on the morphometrical and biomechanical analyses of
the stentless bioprosthesis, we demonstrated that there are differences in wall
thickness and elasticity between each sinus of Valsalva. These differences
suggest that the non-coronary sinus of Valsalva is the most vulnerable and at
greater risk of tissue failure. The exclusion of the non-coronary sinus of
Valsalva may be beneficial to mitigate the long-term risks of tissue failure in
the stentless bioprosthesis.
PMID- 29956051
TI - Sleep disorders in Cimarosa's "The Secret Marriage".
PMID- 29956052
TI - Religiosity and Subjective Well-Being of the Central and Eastern European's
Elderly Population.
AB - The paper examines the relation between religiosity and cognitive appraisal of
the subjective well-being of the Central and Eastern European's elderly
population. The first part of the paper is dedicated to examining of the
scientific literature. In the second part, the authors explore the data basis
corresponding to the 6th wave of World Value Survey. The authors use the
heterogeneous correlation and the multi-linear regression analysis in order to
explain the relation between religiosity and subjective well-being of the old
aged. Our results suggest that in the case of the Central Eastern European
elderly satisfaction with life is mostly influenced by health and income. It is
likely that for Central and Eastern European's elders religious practices do not
sufficiently influence their life satisfaction.
PMID- 29956053
TI - Putting the Spirit into Culturally Responsive Public Health: Explaining Mass
Fainting in Cambodia.
AB - The study explores the cultural and religious meaning behind episodes of mass
fainting sweeping through garment factories in Cambodia. An ethnographic study
was conducted at 20 garment factories in Kandal, Preah Sihanouk, Kampong Cham,
Kampong Speu, Takeo, and Kampong Chhnang provinces. Informants were 50 women who
fainted or possessed and their families, factory and clinic staff, and monks.
Informants described their views on the causes of the mass fainting. Based on the
informants' views, the seeds were sown when factories were built on former Khmer
Rouge killing fields, when local guardian spirits were disrespected and when the
factories were not inaugurated with the proper rituals. We found that an
inauspicious death, a conflict leading to violation of a vow, or culturally
inappropriate interventions by management explained what triggered the episodes.
The results show that people believe that mass faintings occur in parallel with
tensions between the workers and the foreign owners of the factories and tensions
between the human and spiritual owners of the land. The study has implications
for the development of culturally responsive public health interventions in mass
group phenomena.
PMID- 29956054
TI - Religiousness and Diseases in Europe: Findings from SHARE.
AB - Recent research in religiousness and health suggests that epidemiological forces
can have opposed effects. Here we examine two forms of religiousness and their
association with disease. We performed a cross-sectional study of 23,864 people
aged 50+ included in wave 1 (2004-2005) of the Survey of Health, Ageing and
Retirement in Europe and a longitudinal study including people from wave 1, who
were followed up during 11 years. Results suggested that taking part in a
religious organization was associated with lower odds of heart attack (OR 0.74,
95% CI 0.60, 0.90), stroke (OR 0.68, 95% CI 0.50, 0.95), and diabetes (OR 0.72,
95% CI 0.58, 0.90) and longitudinally associated with lower odds of cancer (OR
0.78, 95% CI 0.60, 1.00). Conversely, praying was longitudinally associated with
higher odds of heart attack (OR 1.27, 95% CI 1.10, 1.48) and high cholesterol (OR
1.12, 95% CI 1.00, 1.26). The most religious people had lower odds of stroke,
diabetes, and cancer than other respondents, and in the longitudinal model,
people who only prayed had higher odds of heart attack than non-religious people.
Our findings lend support to the hypothesis that restful religiousness (praying,
taking part in a religious organization, and being religiously educated) was
associated with lower odds of some diseases, whereas little evidence was present
that crisis religiousness (praying only) was associated with higher odds of
disease.
PMID- 29956055
TI - Cabozantinib-induced serum creatine kinase elevation and musculoskeletal
complaints.
AB - Cabozantinib is a multikinase inhibitor approved for the treatment of metastatic
medullary thyroid cancer and advanced renal cell carcinoma (RCC) in patients who
have received prior anti-angiogenic therapy. While associations between serum
creatine kinase (CK) elevations and other tyrosine kinase inhibitors used for the
treatment of solid malignancies have been previously reported, we report a case
of cabozantinib-associated CK elevation that was associated with musculoskeletal
complaints by an RCC patient. Nine days following initiation of cabozantinib, the
patient reported muscle cramps and serum CK had increased from levels 12 months
earlier that were within normal limits to a grade 1 elevation of 244 units/L.
Despite a dose reduction, her CK continued to rise over the next 2 months,
leading to a peak CK of 914 units/L. Due to this grade 3 elevation, cabozantinib
was permanently discontinued, and her CK subsequently returned to a grade 1
elevation within one week and then to baseline within 3 weeks. The temporal
relationship between drug exposure and CK increase strongly suggests causality.
To the authors' knowledge, this is the first reported case of CK elevation
attributed to cabozantinib, but cabozantinib-induced CK elevations could be under
reported, and providers should monitor for musculoskeletal complaints during
cabozantinib therapy.
PMID- 29956056
TI - Oral Metronomic Vinorelbine (OMV) in elderly or pretreated patients with advanced
non small cell lung cancer: outcome and pharmacokinetics in the real world.
AB - Background Oral metronomic therapy (OMV) is particularly suitable for palliative
care, and schedules adapted for unfit patients are advisable. This study
investigated the effects of oral vinorelbine given every other day without
interruption and its pharmacokinetic profile in patients with advanced lung
cancer. Materials and Methods Ninety-two patients received OMV at doses of 20, 30
or 50 mg. Toxic events, clinical benefit and overall survival were analysed.
Blood pharmacokinetics were evaluated in 82 patients. Results Median treatment
duration and overall survival were 15 (range 1.3-144) and 32.3 weeks,
respectively; fourty-eight (60%) patients experienced clinical benefit. Outcomes
were unrelated to previous therapies, age, histology or comorbidities. Toxicity
was associated with higher blood concentrations of the drug. Pharmacokinetics
were stable for up to two years, and were not influenced by treatment line or
age. Conclusions OMV produced non-negligible survival in patients and also showed
stable long-term blood concentrations. The schedule of 20-30 mg every other day
without interruption gave good tolerability and clinical benefit.
PMID- 29956057
TI - Impact of fluid challenge increase in cardiac output on the relationship between
systemic and cerebral hemodynamics in severe sepsis compared to brain injury and
controls.
AB - BACKGROUND: Cognitive dysfunction and delirium after ICU are frequent and may
partially result from brain ischemia episodes. We hypothesized that systemic
inflammation (severe sepsis or septic shock) modifies the control of brain
circulation and the relation between systemic and cerebral hemodynamic after a
positive response to fluid challenge (FC). METHODS: Three groups of patients were
studied if they increased stroke volume (SV) > 10% after 250 or 500 ml of
crystalloids: control group: patients free of comorbidity anesthetized for
orthopedic surgery; sepsis group: patients with severe sepsis or septic shock
(classic definition); brain injury (BI) group: trauma brain jury or hemorrhagic
stroke with no detectable systemic inflammation. The measurements before and
after FC were mean arterial blood pressure (MAP) (radial catheter); SV and
cardiac output (CO; transesophageal Doppler); bilateral middle cerebral artery
(MCAv) velocity with peak systolic (PSV) and end diastolic (EDV) values
(transcranial Doppler); end-tidal CO2. The role of MAP increase was investigated
by an arbitrarily threshold increase of 5%, called responder in CO and MAP (RR).
The remaining patients were call responders in CO and non-responders in MAP
(RnR). Nonparametric tests were used for statistical analysis. RESULTS: Among the
86 screened patients, 66 have completed the protocol: 17 in control group; 38 in
sepsis group; and 11 in BI group. All patients increased SV > 10% after FC. Only
the sepsis group increased MAP [+ 12 (2-25%), p < 0.05] with a significant
increase in PSV and EDV [(17 (3-30)% and 17 (12-42)%, respectively (p < 0.05)],
which did not change in the two other groups. The septic RR or RnR had similar
variations in MCAv after FC. The baseline MAP < or > baseline median MAP had
similar MCAv. CONCLUSIONS: After a FC-induced increase in SV, MCAv (PSV and EDV)
increased only in septic group, mostly independently from MAP increase and from
baseline MAP level. Cerebral perfusion becomes passively dependent on systemic
blood flow, suggesting a modification of the control of cerebrovascular tone in
sepsis-induced systemic inflammation. This information has been considered in the
clinical management of septic patients.
PMID- 29956058
TI - Blockchain-Based Data Preservation System for Medical Data.
AB - Medical care has become an indispensable part of people's lives, with a dramatic
increase in the volume of medical data (e.g., diagnosis certificates and medical
records). Medical data, however, is easily stolen, tampered with, or even
completely deleted. If the above occurs, medical data cannot be recorded or
retrieved in a reliable manner, resulting in delay treatment progress, even
endanger the patient's life. In this paper, we propose a novel blockchain-based
data preservation system (DPS) for medical data. To provide a reliable storage
solution to ensure the primitiveness and verifiability of stored data while
preserving privacy for users, we leverage the blockchain framework. With the
proposed DPS, users can preserve important data in perpetuity, and the
originality of the data can be verified if tampering is suspected. In addition,
we use prudent data storage strategies and a variety of cryptographic algorithms
to guarantee user privacy; e.g., an adversary is unable to read the plain text
even if the data are stolen. We implement a prototype of the DPS based on the
real world blockchain-based platform Ethereum. Performance evaluation results
demonstrate the effectiveness and efficiency of the proposed system.
PMID- 29956059
TI - Can a Brief Telephone Intervention for Problem Gambling Help to Reduce Co
existing Depression? A Three-Year Prospective Study in New Zealand.
AB - Problematic gambling and depression commonly co-exist, with limited research
indicating that depression and/or psychological distress appear to reduce with
brief interventions for problem gambling. The present study was designed to
examine the effect, over 36 months, of a brief problem gambling intervention on
depression in a population of people seeking help for gambling issues. One
hundred and thirty-one participants were recruited from adult (18+ years) gambler
callers to the New Zealand national gambling helpline. They received a manualised
version of the helpline's brief intervention, and were assessed at baseline, 12
and 36 months. Overall, problem gambling severity reduced from a score of 17
(using the Problem Gambling Severity Index) at baseline to a score of 7.5 at 36
months. The percentage of participants with depression reduced from 74% at
baseline to 41% at 36 months. For both problem gambling and depression, the
greatest reduction was in the first 12 months. Multiple logistic regression
analyses at baseline showed an association between problem gambling and
depression. Repeated measures logistic regression indicated that reduced problem
gambling severity reduced depression and that there was no independent time
effect taking place (i.e. the decreased depression was not due to natural
recovery). Thus a single brief telephone intervention for problem gambling
substantially reduced the prevalence of depression. This has clinical and public
health implications with a benefit being that people with depression and co
existing gambling problems may not necessarily need additional treatment for
depression if they receive treatment for their gambling issues.
PMID- 29956060
TI - Effectiveness of irrigation strategies on the removal of the smear layer from
root canal dentin.
AB - The aim of this study was to evaluate the removal of the smear layer by some
commonly used (needle-and-syringe irrigation, sonic activation, ultrasonically
activated irrigation) and new root canal irrigation strategies (negative pressure
irrigation and polymer rotary file) using a novel approach by comparing pre- and
post-experimental images. Prepared root canals (n = 50) were subjected to a split
tooth model and divided into 5 groups (n = 10): (1) needle-and-syringe irrigation
(control); (2) sonic activation (SA); (3) negative pressure irrigation with
continuous warm activated irrigation and evacuation (CWA); (4) polymer finishing
file (FF); (5) ultrasonically activated irrigation (UAI). Smear layer scores and
percentage of open dentinal tubules (%ODT) were evaluated by 2 examiners before
and after irrigation procedures, from the middle and apical thirds of the root
canal, on scanning electron microscopic images. Data were analysed using Kruskal
Wallis and post hoc tests at P = 0.05. Needle-and-syringe irrigation (control)
showed no significant difference (both smear score and %ODT) compared to the pre
experimental value (P > 0.05). All other groups showed lower smear scores and
higher %ODT, compared to the control (P < 0.05). The lowest smear score and
highest %ODT were observed in the CWA group, which was significantly different
from all other groups (P < 0.05). SA group showed significantly higher smear
scores and lower %ODT than FF or UAI (P < 0.05). CWA showed superior removal of
smear layer in the middle and apical thirds of the root canal compared to the
other irrigation strategies.
PMID- 29956061
TI - Towards Secure and Privacy-Preserving Data Sharing in e-Health Systems via
Consortium Blockchain.
AB - Electronic health record sharing can help to improve the accuracy of diagnosis,
where security and privacy preservation are critical issues in the systems. In
recent years, blockchain has been proposed to be a promising solution to achieve
personal health information (PHI) sharing with security and privacy preservation
due to its advantages of immutability. This work proposes a blockchain-based
secure and privacy-preserving PHI sharing (BSPP) scheme for diagnosis
improvements in e-Health systems. Firstly, two kinds of blockchains, private
blockchain and consortium blockchain, are constructed by devising their data
structures, and consensus mechanisms. The private blockchain is responsible for
storing the PHI while the consortium blockchain keeps records of the secure
indexes of the PHI. In order to achieve data security, access control, privacy
preservation and secure search, all the data including the PHI, keywords and the
patients' identity are public key encrypted with keyword search. Furthermore, the
block generators are required to provide proof of conformance for adding new
blocks to the blockchains, which guarantees the system availability. Security
analysis demonstrates that the proposed protocol can meet with the security
goals. Furthermor, we implement the proposed scheme on JUICE to evaluate the
performance.
PMID- 29956062
TI - Thermal analysis of the dentine tubule under hot and cold stimuli using fluid
structure interaction simulation.
AB - The objective of this study is to compare the thermal stress changes in the tooth
microstructures and the hydrodynamic changes of the dental fluid under hot and
cold stimuli. The dimension of the microstructures of eleven cats' teeth was
measured by scanning electron microscopy, and the changes in thermal stress
during cold and hot stimulation were calculated by 3D fluid-structure interaction
modeling. Evaluation of results, following data validation, indicated that the
maximum velocities in cold and hot stimuli were - 410.2 +/- 17.6 and + 205.1 +/-
8.7 um/s, respectively. The corresponding data for maximum thermal stress were -
20.27 +/- 0.79 and + 10.13 +/- 0.24 cmHg, respectively. The thermal stress caused
by cold stimulus could influence almost 2.9 times faster than that caused by hot
stimulus, and the durability of the thermal stress caused by hot stimulus was 71%
greater than that by cold stimulus under similar conditions. The maximum stress
was on the tip of the odontoblast, while the stress in lateral walls of the
odontoblast and terminal fibril was very weak. There is hence a higher
possibility of pain transmission with activation of stress-sensitive ion channels
at the tip of the odontoblast. The maximum thermal stress resulted from the cold
stimulus is double that produced by the hot stimulus. There is a higher
possibility of pain transmission in the lateral walls of the odontoblast and
terminal fibril by releasing mediators during the cold stimulation than the hot
stimulation. These two reasons can be associated with a greater pain sensation
due to intake of cold liquids.
PMID- 29956063
TI - Change in staff anesthesiologists' opinions of an Anesthesia Information
Management System (AIMS).
AB - Following introduction of an Anesthesia Information Management System (AIMS) at a
tertiary care, academic health sciences centre, a quality assurance initiative
was conducted to assess staff opinions of the AIMS using a previously published,
anonymous survey tool at 1 and 5 years following AIMS introduction. At 5 years
compared to 1 year after implementation of AIMS, the majority (18 of 24, 75%) of
responses to the survey questions had a statistically significant change (P <
0.05) in the proportion of respondents favoring AIMS compared to the 1 year
survey. Domains noted to be more favorable 5 years compared to 1 year after AIMS
introduction included patient safety in the Operating Rooms and Post-Anesthesia
Care Unit, quality of handover and overall documentation, and communication
amongst healthcare workers. The ideal time period at which to assess AIMS after
introduction is not clear.
PMID- 29956064
TI - Orphan Nuclear Receptors in Colorectal Cancer.
AB - Colorectal cancer is one of the most common cancers worldwide, with an overall
increased incidence annually. Despite improvements in treatment and surveillance,
almost 50% develop recurrent and/or distant disease. Unknown cellular processes
are the fundamental cause for treatment failure and metastatic disease. The
interplay of chronic inflammation and carcinogenesis is well established. Recent
work has highlighted the role of nuclear receptors and co-regulators in the
inflammation to carcinogenesis process. Orphan nuclear receptors have been shown
to be involved in numerous cellular processes, including both at a
transcriptional and a non-genomic level. There is a significant emphasis to
identify ligands that will interact and modify these nuclear receptors, with the
long-term aim of developing novel pharmaceutical therapies. The identification of
orphan nuclear receptor ligands will also help increase our current understanding
of their role in cellular signaling, by enabling manipulation of these receptors.
This review aims to provide a brief overview of some key orphan nuclear receptors
which may be involved in colorectal cancer.
PMID- 29956065
TI - NOAC in "real world" patients with atrial fibrillation in Italy: results from the
ISPAF-2 (Indagine Sicoa Paziente Con Fibrillazione Atriale) survey study.
AB - In the past few years, new oral anticoagulants (NOACs) targeting directly a
single activated clotting factor, have been developed for the treatment of non
valvular atrial fibrillation (AF), which are currently recommended as first-line
therapy in AF. The aim of this study is to provide an overall picture on the
extent to which oral anticoagulation (OAC) with NOACs correspond to actually
prescribed OAC therapy in an unselected, real world, population of consecutive
patients with AF in Italy. Compliance with the therapy and quality of life were
also assessed. A 50 cardiology unit network located in different geographic areas
of Italy enrolled a total of 1742 consecutive outpatients with AF (54.6% males,
45.4% females, mean age 72.5 years). NOACs were prescribed in 56.1% patients and
VKA in 43.9% (P < 0.0001). NOACs were significantly more prescribed than VKA in
patients with high thrombo-embolic risk score (i.e., CHA2DS2-VASc > 2) (78.2 vs
67.3%, P < 0.0001), but also patients at low risk (i.e., CHA2DS2-VASc < 1 and HAS
BLED < 3) were still under OAC therapy with either NOACs (27%) or VKA (73%).
Adherence to therapy (Morisky test) was greater in patients taking NOACs as was
the quality of life. The ISPAF-2 study shows that in an Italian population of
real-world patients with AF the prescription of OAC according to current
guidelines and stroke-risk scoring system is rather high although it still needs
to be improved. Contrary to recommendations, in a high proportion of low-risk
patients, anticoagulation therapy, with either NOACs and VKA is still prescribed,
and this exposes patients to unjustified risks.
PMID- 29956066
TI - Increased High Molecular Weight FGF2 in Endocrine-Resistant Breast Cancer.
AB - Endocrine resistance may develop as a consequence of enhanced growth factor
signaling. Fibroblast growth factor 2 (FGF2) consists of a low and several high
molecular weight forms (HMW-FGF2). We previously demonstrated that antiprogestin
resistant mammary carcinomas display lower levels of progesterone receptor A
isoforms (PRA) than B isoforms (PRB). Our aim was to evaluate the role of FGF2
isoforms in breast cancer progression. We evaluated FGF2 expression, cell
proliferation, and pathway activation in models with different PRA/PRB ratios. We
performed lentiviral infections of different FGF2 isoforms using the human
hormone-responsive T47D-YA cells, engineered to only express PRA, and evaluated
tumor growth, metastatic dissemination, and endocrine responsiveness. We assessed
FGF2 expression and localization in 81 human breast cancer samples. Antiprogestin
resistant experimental mammary carcinomas with low PRA/PRB ratios and T47D-YB
cells, which only express PRB, displayed higher levels of HMW-FGF2 than
responsive variants. HMW-FGF2 overexpression in T47D-YA cells induced increased
tumor growth, lung metastasis, and antiprogestin resistance compared to control
tumors. In human breast carcinomas categorized by their PRA/PRB ratio, we found
nuclear FGF2 expression in 55.6% of tumor cells. No differences were found
between nuclear FGF2 expression and Ki67 proliferation index, tumor stage, or
tumor grade. In low-grade tumor samples, moderate to high nuclear FGF2 levels
were associated to carcinomas with low PRA/PRB ratio. In conclusion, we show that
HMW-FGF2 isoforms are PRB targets which confer endocrine resistance and are
localized in the nuclei of breast cancer samples. Hence, targeting intracellular
FGF2 may contribute to overcome tumor progression.
PMID- 29956067
TI - IL-1beta Enhances Wnt Signal by Inhibiting DKK1.
AB - Aberrant endochondral bone formation in the physis is a unique bone lesion in
neonatal-onset multisystem inflammatory disease (NOMID), also called chronic
infantile neurologic cutaneous articular (CINCA), the most severe of the
cryopyrin-associated periodic syndrome (CAPS) diseases, which are interleukin
1beta (IL-1beta)-related monogenic autoinflammatory diseases. The wingless (Wnt)
pathway plays an important role in osteoblast differentiation. In this study, we
explored the potential role of IL-1beta on the expression of WNT genes and the
Wnt antagonist Dickkopf-1 (DKK1). The expression of WNT and DKK1 in fibroblast
like synoviocytes (FLS), which are articular resident cells, was quantified by
quantitative PCR and enzyme-linked immunosorbent assay. Additionally, we used T
cell factor (TCF) reporter assays to evaluate the activity of the canonical Wnt
signal pathway in the presence or absence of the supernatant of cultured FLS
treated with or without IL-1beta and IL-6. Anti-DKK1 antibodies were used to
neutralize DKK1. The expression of both canonical and non-canonical WNT genes as
well as DKK1 was observed in FLS. The supernatant of cultured FLS suppressed the
luciferase activity of the TCF reporter, and this effect was reduced by its pre
treatment with an anti-DKK1 antibody. Both IL-1beta and IL-6 significantly
reduced DKK1 production. Furthermore, the supernatant of FLS cultured with IL
1beta or IL-6 showed a reduced inhibitory effect on Wnt signaling, compared with
the supernatant of untreated FLS. These data suggest that IL-1beta, like IL-6,
dampens DKK1 production, and thereby promotes Wnt signal activation. Therefore,
increased levels of IL-1beta may contribute to the dysregulation of endochondral
ossification in NOMID/CINCA.
PMID- 29956068
TI - Interleukin-37 Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis
in Mice.
AB - Pulmonary fibrosis is a disease with chronic inflammation and excessive collagen
deposition for which there is no effective treatments. Interleukin (IL)-37 is a
newly identified anti-inflammatory cytokine but its role in pulmonary fibrosis
remains unclear. In this study, we investigated the effect of IL-37 on bleomycin
induced pulmonary fibrosis in mice. A lentivirus expressing IL-37 was
administered intranasally to bleomycin-induced C57BL/6 mice. We found that IL-37
improved the survival of mice and reduced the body weight loss of mice caused by
bleomycin. Furthermore, IL-37 significantly attenuated pulmonary inflammatory
infiltration and collagen deposition and decreased the hydroxyproline content in
bleomycin-treated mice. Finally, IL-37 treatment inhibited the expression of
monocyte chemoattractant protein-1, IL-6, and tumor necrosis factor-alpha, but
increased the expression of interferon-gamma in lung tissues from bleomycin
challenged mice. Taken together, these results suggest that in vivo expression of
IL-37 is useful in preventing pulmonary fibrosis induced by bleomycin and
provides a possible therapeutic approach to pulmonary fibrosis diseases.
PMID- 29956070
TI - Partial Depletion of Regulatory T Cells Enhances Host Inflammatory Response
Against Acute Pseudomonas aeruginosa Infection After Sepsis.
AB - Immune dysfunction contributes to secondary infection and worse outcomes in
sepsis. Regulatory T cells (Tregs) have been implicated in sepsis-induced
immunosuppression. Nevertheless, the role of Tregs in secondary infection after
sepsis remains to be determined. In the present study, a two-hit model which
mimics clinical conditions was used and the potential role of Tregs in secondary
Pseudomonas aeruginosa infection post-sepsis was investigated. Results showed
that mice were susceptible to secondary P. aeruginosa infection 3 days, but not 7
days, post-cecal ligation and puncture (CLP). The levels of IL-17A, IL-1beta, and
IL-6 remained low in CLP mice after P. aeruginosa infection, while the levels of
IL-10 increased significantly. Additionally, increased number of Tregs in both
lung and spleen was observed in "two-hit" mice. Injection with PC61 (anti-CD25)
mAb reduced the number of Tregs by 50% in spleen and 60% in lung of septic mice.
This partial depletion of Tregs elevated IL-17A, IL-1beta, and IL-6 production
and decreased IL-10 levels in septic mice with P. aeruginosa infection, leading
to lower bacterial load, attenuation of lung injury, and improvement of survival.
The present findings demonstrate that Tregs play a crucial role in secondary P.
aeruginosa infection after sepsis by modulating the inflammatory response.
PMID- 29956069
TI - Mechanisms of Hemolysis During Sepsis.
AB - Cell-free hemoglobin is increasingly playing a more central role in the
pathogenesis of sepsis being proved to be a potent predictor of patient's
outcome. It is crucial, hence, to further investigate the mechanisms of sepsis
induced hemolysis with the aim of deriving possible therapeutic principles.
Herein, we collected the most important previously known triggers of hemolysis
during sepsis, which are (1) transfusion reactions and complement activation, (2)
disseminated intravascular coagulation, (3) capillary stopped-flow, (4)
restriction of glucose to red blood cells, (5) changes in red blood cell membrane
properties, (6) hemolytic pathogens, and (7) red blood cell apoptosis. Graphical
Abstract ?.
PMID- 29956071
TI - PI3K/AKT and CD40L Signaling Regulate Platelet Activation and Endothelial Cell
Damage in Sepsis.
AB - Platelets contribute to inflammation and their activation has been suggested as
versatile effectors of sepsis. Activation of platelets promotes secretion of
CD40L that induces sepsis and multiple organ dysfunction syndrome (MODS).
However, the mechanisms regulate platelet-derived CD40L are not fully understood.
Activation of PI3K/Akt pathway has been reported as a key component of sepsis,
whereas the role of PI3K/Akt pathway in platelet-derived CD40L is unknown. In
this study, we identified PI3K/Akt pathway as a key regulator of CD40L secretion
by platelets. Significantly, inhibition of PI3K/Akt pathway by Ly294002
attenuated platelet activation and CD40L production. Moreover, PI3K/Akt pathway
blocking suppresses vascular endothelial cells in vivo. Furthermore, the
expression of biomarkers that represent the severity of sepsis, such as ICAM-1,
VCAM-1, and E-selectin, was also suppressed by Ly294002. Altogether, our results
confirm the pivotal role of PI3K/Akt pathway in sepsis and its inhibition might
be a potential therapeutic target.
PMID- 29956072
TI - Measuring Activation in Parents of Youth with Emotional and Behavioral Disorders.
AB - For parents of youth with emotional and behavioral disorders, activation, or
having the knowledge, skills, and confidence to access and engage in appropriate
services for their children, is important for managing their child's mental
health care. The Parent Activation Measure (PAM) was modified to create the
Parent Patient Activation Measure-Mental Health (P-PAM-MH) to measure activation
as part of a randomized controlled trial of a peer parent support intervention
for parents of youth with emotional and behavioral problems. Results from this
study provide initial support for use of the P-PAM-MH as a measure of activation
in this population and for the reliability and validity of the measure.
Implications of the findings from this study for research and practice in
behavioral health are discussed.
PMID- 29956073
TI - iTRAQ-based proteomic analysis of DMH-induced colorectal cancer in mice reveals
the expressions of beta-catenin, decorin, septin-7, and S100A10 expression in 53
cases of human hereditary polyposis colorectal cancer.
AB - PURPOSE: The aim of this study is to explore the roles of beta-catenin, decorin,
septin-7, and S100A10 expression in colorectal cancer development. METHODS:
Twenty-five BALB/c mice were divided into five groups; four groups were
administrated N,N-dimethylhydrazine for 0, 10, 15, and 20 weeks, and one group
was administrated normal saline for 20 weeks. The colons were collected for
histopathological analysis. Protein samples prepared from the frozen colon
tissues of mice treated with N,N-dimethylhydrazine for the different time points
were evaluated using the isobaric tags for relative and absolute quantification
(iTRAQ) labeling technique coupled with the 2D liquid chromatography-tandem mass
spectrometry analysis. Based on the proteomic analysis results,
immunohistochemical staining of beta-catenin, decorin, septin-7, and S100A10 was
performed in paraffin-embedded mice colorectal tissue, and 53 cases of human
hereditary polyposis colorectal cancer samples. RESULTS: Colorectal cancer was
observed in mice treated with N,N-dimethylhydrazine for 20 weeks, and adenomas
were observed in mice subjected to the 10-, and 15-week treatments. Seventy-two
differentially expressed proteins were involved in the development of cancer as
per the iTRAQ and spectrometry analysis. In normal epithelium, adenoma, and
cancer from human hereditary polyposis colorectal cancer, S100A10 expression (c2
= 100.989, P = 0.000) was highest in cancer, whereas decorin (c2 = 12.852, P =
0.002) and septin-7 (c2 = 66.519, P = 0.002) expressions were highest in the
normal epithelium, which was confirmed via immunohistochemical staining.
CONCLUSIONS: The subcellular localization of beta-catenin and decorin, septin-7,
and S100A10 expressions are associated with the development of colorectal cancer
in mice after N,N-dimethylhydrazine treatment and in human hereditary polyposis
colorectal cancers.
PMID- 29956074
TI - Outcomes of early-stage breast cancer patients treated with sequential
anthracyclines-taxanes in relationship to relative dosing intensity: a secondary
analysis of a randomized controlled trial.
AB - PURPOSE: To assess the impact of relative dosing intensity (RDI) on the outcomes
of breast cancer patients referred for adjuvant anthracycline-taxane
chemotherapy. METHODS: This is a secondary analysis of the outcomes of patients
in the comparator arm of the BCIRG005 study who received adjuvant
adriamycin/cyclophosphamide (AC)-docetaxel regimen. Overall survival was assessed
according to RDI through Kaplan-Meier analysis. Univariate and multivariate
analyses of parameters affecting overall survival were then conducted through Cox
regression analysis. RESULTS: Kaplan-Meier analysis of overall survival according
to RDI for the AC-docetaxel regimen (< 90 vs. >= 90%) was conducted and it showed
that RDI < 90% is associated with worse overall survival (P = 0.006). In
univariate Cox regression analysis, the following parameters significantly
affected overall survival (P < 0.05): age, T stage, lymph node ratio, hormone
receptor status, and grade of the disease and RDI for AC-docetaxel regimen. When
these factors were included in multivariate analysis, the following factors were
associated with worse overall survival: age less than 40 years (P < 0.0001),
greater T stage (P < 0.0001), greater lymph node ratio (P < 0.0001), negative
hormone receptor status (P = 0.001), high grade (P < 0.0001) and RDI <= 90% (P =
0.015). Formal interaction testing between RDI and hormone receptor status has a
non-significant P value (P = 0.794). CONCLUSION: Lower RDI for the whole
anthracycline-taxane protocol is associated with worse patient survival. Every
effort should be exercised to avoid unnecessary dose reductions and/or
interruptions among early breast cancer patients receiving adjuvant anthracycline
taxane chemotherapy.
PMID- 29956075
TI - Prevalence and Predictors of Invasive Fungal Infections in Children with
Persistent Febrile Neutropenia Treated for Acute Leukemia - A Prospective Study.
AB - OBJECTIVE: To ascertain the prevalence of invasive fungal infections (IFI),
predictors of IFI, identify etiological species and outcome (mortality/discharge)
in persistent febrile neutropenia in children with acute leukemia. METHODS: It
was a prospective, observational study conducted from January 2013 through June
2014 in a tertiary care centre in New Delhi. Children between 1 and 12 y of age,
on chemotherapy for acute leukemia with persistent febrile neutropenia (> 96 h)
were enrolled. These children were not on any antifungal prophylaxis. Diagnosis
of IFI was based on European Organization for Research and Treatment of Cancer
and Mycoses Study Group (EORTC/MSG) criteria. Prevalence and outcome was reported
in mean +/- 95% CI form and etiological species were presented in the form of the
frequency distribution. RESULTS: Three hundred nineteen episodes involving 187
children of febrile neutropenia were screened and 74 were enrolled. Prevalence of
IFI was 22.97% (13.99-34.21). Positive cases were further classified into proven
3(17.6%), probable 11(64.8%) and possible 3(17.6%) according to EORTC/MSG
criteria. On multivariate analysis, abnormal CXR and clinical sinusitis were
important predictors of IFI. Most common fungi isolated was Aspergillus sp.
followed by Candida sp. Mortality rate was 9.45% (3.89-18.52). CONCLUSIONS: Thus,
prevalence of IFI is very high in children with persistent febrile neutropenia
who are not on antifungal prophylaxis. Abnormal chest x- ray and clinical
sinusitis are important predictors of IFI.
PMID- 29956076
TI - Shoot shovel and sanction yourself: Self-policing as a response to wolf poaching
among Swedish hunters.
AB - Self-policing is essential for addressing wildlife-related crime where illegal
activity is extremely diffuse, and limited resources are available for monitoring
and enforcement. Emerging research on self-policing suggest key drivers including
economics, folk traditions, and socio-political resistance. We build on this
research with a case study evaluating potential drivers of self-policing illegal
wolf killing among Swedish hunting teams. Swedish hunters marginally leaned
toward considering illegal hunting of wolves an expression of resistance (10.30
out of a possible 17 on a resistance scale) and strongly believed outsiders had
undue influence over hunting (15.79 out of a possible 21 on an influence scale).
Most (73%) Swedish hunters stated they would report illegal wolf killing to
authorities, but 20% stated they would handle the infractions through internal
sanctions. Viewing illegal hunting of wolves as a form of political resistance,
viewing wolf management as being controlled locally, and perceived prevalence of
illegal wolf killing among hunting acquaintances were positive predictors of
preferring internal sanctions to address illegal wolf killing over reporting the
crimes. Resistance and perceived prevalence of wolf killing also predicted
preferring no action to address illegal wolf killing. These results suggest that
a counterpublic of marginalized ruralism may promote forms of self-policing that
rely on internal censure for illegal wolf killing rather than using formal legal
channels. Similarly, folk traditions within this counterpublic (e.g., perceptions
of prevalence of illegal wolf killing) shape if and how internal sanctions are
advocated. Re-engaging marginalized hunting groups and emphasizing the rarity of
illegal wolf killing may promote wolf conservation, both in Sweden and in other
democratic regimes.
PMID- 29956077
TI - Context Matters: Revisiting the First Step of the 'Sequence of Prevention' of
Sports Injuries.
AB - It is possible to prevent sports injuries. Unfortunately, the demonstrated
efficacy and effectiveness of injury prevention approaches are not translated
into lasting real-world effects. Contemporary views in sports medicine and injury
prevention suggest that sports injuries are 'complex' phenomena. If the problem
we aim to prevent is complex, then the first step in the 'sequence of prevention'
that defines the 'injury problem' already needs to have considered this. The
purpose of this paper is to revisit the first step of the 'sequence of
prevention', and to explore new perspectives that acknowledge the complexity of
the sports injury problem. First, this paper provides a retrospective of the
'sequence of prevention', acknowledging contemporary views on sports injuries and
their prevention. Thereafter, from the perspective of the socioecological model,
we demonstrate the need for taking into account the complex nature of sports
injuries in the first step. Finally, we propose an alternative approach to
explore and understand injury context through qualitative research methods. A
better understanding of the injury problem in context will guide more context
sensitive studies, thus providing a new perspective for sports injury prevention
research.
PMID- 29956078
TI - Severe Congenital Neutropenia associated with SRP54 mutation in 22q11.2 Deletion
Syndrome: Hematopoietic Stem Cell Transplantation Results in Correction of
Neutropenia with Adequate Immune Reconstitution.
PMID- 29956079
TI - The Treatment of Inflammatory Bowel Disease in Patients with Selected Primary
Immunodeficiencies.
AB - The gastrointestinal tract is heavily populated with innate and adaptive immune
cells that have an active role in preservation of mucosal homeostasis and
prevention of inflammation. Inflammatory bowel diseases are thought to result
from dysregulated immune function that is influenced by genetic background,
environmental triggers, and microbiome changes. While most inflammatory bowel
disease patients present in adolescent years or adulthood, in a minority of
cases, the disease develops early in life, and in some of these young patients, a
monogenic disease causing intestinal inflammation can be identified. Many of
these conditions result from mutations in immune-mediated genes and can present
with or without concomitant recurrent infections. In this review, we will discuss
the treatment of patients with selected primary immunodeficiencies and
inflammatory bowel diseases. We will focus on five conditions resulting from
mutations in IL10/IL10 receptor, NADPH oxidase complex, XIAP, LRBA, and CTLA-4.
PMID- 29956080
TI - Histology and Transcriptome Profiles of the Mammary Gland across Critical Windows
of Development in Sprague Dawley Rats.
AB - Breast development occurs through well-defined stages representing 'windows of
susceptibility' to adverse environmental exposures that potentially modify breast
cancer risk. Systematic characterization of morphology and transcriptome during
normal breast development lays the foundation of our understanding of cancer
etiology. We examined mammary glands in female Sprague Dawley rats across six
developmental stages - pre-pubertal, peri-pubertal, pubertal, lactation, adult
parous and adult nulliparous. We investigated histology by Hematoxylin and Eosin
and Mallory's Trichrome stain, proliferative and apoptotic rate by
immunohistochemistry and whole-transcriptome by microarrays. We identified
differentially expressed genes between adjacent developmental stages by linear
models, underlying pathways by gene ontology analysis and gene networks and hubs
active across developmental stages by coexpression network analysis. Mammary
gland development was associated with large-scale changes in the transcriptome;
particularly from pre-pubertal to peri-pubertal period and the lactation period
were characterized by distinct patterns of gene expression with unique biological
functions such as immune processes during pre-pubertal development and
cholesterol biosynthesis during lactation. These changes were reflective of the
shift in mammary gland histology, from a rudimentary organ during early stages to
a secretory organ during lactation followed by regression with age. Hub genes
within mammary gene networks included metabolic genes such as Pparg during the
pre-pubertal stage and tight junction-related genes claudins and occludins in
lactating mammary glands. Transcriptome profile paired with histology enhanced
our understanding of mammary development, which is fundamental in understanding
the etiologic mechanism of breast cancer, especially pertaining to windows of
susceptibility to environmental exposures that may alter breast cancer risk.
PMID- 29956083
TI - The Association Between Fraternal Birth Order and Anal-Erotic Roles of Men Who
Have Sex with Men.
AB - The fraternal birth order effect (FBOE) describes the phenomenon that homosexual
men tend to have a greater number of older brothers than do heterosexual men. The
FBOE is a marker for an innate, biological predisposition for androphilia in
genotypic males. The FBOE has been studied since the 1930s and is the most
consistent biodemographic correlate of sexual orientation in men. This study
sought to determine whether the FBOE applies equally to all men who have sex with
men (MSM), or disproportionately to MSM whose anal intercourse behavior is
predominantly receptive (Bottoms). Participants included 243 North American adult
MSM who responded to advertisements posted on a Web site and other electronic
media associated with the GALA festival, a quadrennial gathering of gay and
lesbian choruses. Each was asked whether his anal intercourse behavior during the
preceding year was predominantly receptive, predominantly penetrative, or about
equally receptive and penetrative. Those who indicated their behavior was
predominantly receptive were coded "Bottoms"; all others were coded "Not
Bottoms." Participants were also surveyed as to their sibship composition.
Bottoms had a significantly greater mean number of older brothers than did Not
Bottoms. There was no significant difference with respect to older or younger
sisters or younger brothers. Further, the older sibling sex ratio (OSSR) for the
Bottom cohort, but not for the Not-Bottom cohort, was significantly higher than
the expected OSSR for the general male population (OSSR = No. older brothers/No.
older sisters * 100; expected OSSR for general population = 106). Thus, late
fraternal birth order was correlated with receptive anal-erotic behavior among
MSM.
PMID- 29956082
TI - Targeting transcription factors in acute myeloid leukemia.
AB - Transcription factors recognize and bind to consensus sequence elements that are
specific for each transcription factor, and the transcription factors then
regulate downstream gene expression. In the bone marrow, transcription factors,
such as C/EBPalpha, PU.1, and RUNX1, control essential genes to maintain the
normal hematopoietic system. Dysregulation of transcription factors caused by
gene mutations, chromosomal aberrations, or aberrant expression can lead to
cancer, including acute myeloid leukemia. In the past, transcription factors were
not considered "druggable" targets. However, a better understanding of the
pathology of malignant tumors and mechanisms of transcriptional regulation has
enabled us to develop novel therapeutic strategies that target transcription
factors. In this review, we focus on transcription factors that play important
roles in leukemogenesis and current efforts and prospects in the development of
transcriptional therapy. We believe that such a therapeutic approach will benefit
patients with cancers that involve acute myeloid leukemia in the near future.
PMID- 29956081
TI - p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the
FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts.
AB - Reactive oxygen species (ROS) control forkhead box O (FOXO) transcription factor
activity by influencing their nuclear translocation. However, knowledge of the
ROS cellular source(s) involved herein remains scarce. Recently, we have shown
p47phox-dependent activation of ROS-producing NADPH oxidase (NOX) at the nuclear
pore in H9c2 rat cardiomyoblasts in response to ischemia. This localizes NOX
perfectly to affect protein nuclear translocation, including that of
transcription factors. In the current study, involvement of p47phox-dependent
production of ROS in the nuclear translocation of FOXO1 was analyzed in H9c2
cells following 4 h of metabolic inhibition (MI), which mimics the effects of
ischemia. Nuclear translocation of FOXO1 was determined by quantitative digital
imaging fluorescence and western blot analysis. Subsequently, the effect of
inhibiting p47phox-dependent ROS production by short hairpin RNA (shRNA)
transfection on FOXO1 translocation was analyzed by digital-imaging microscopy.
MI induced a significant translocation of FOXO1 into the nucleus. Transfection
with p47phox-shRNA successfully knocked-down p47phox expression, reduced nuclear
nitrotyrosine production, an indirect marker for ROS production, and inhibited
the nuclear translocation of FOXO1 following MI. With these results, we show for
the first time that nuclear import of FOXO1 induced by MI in H9c2 depends
critically on p47phox-mediated ROS production.
PMID- 29956084
TI - Everolimus shortens survival of newly diagnosed glioblastoma patients.
PMID- 29956085
TI - Correction to: Overview of therapeutic plasma exchange in pediatric neurology: a
single-center experience.
AB - Unfortunately, the immediate following sentences were incorrectly published in
Material and Method section of the original article.
PMID- 29956086
TI - Correction to: The effect of CA1 dopaminergic system on amnesia induced by
harmane in mice.
AB - Unfortunately, the second author name was incorrectly published in the original
article. The complete correct name should read as follows.
PMID- 29956087
TI - Patient-Reported Symptoms Over 48 Weeks Among Participants in Randomized, Double
Blind, Phase III Non-inferiority Trials of Adults with HIV on Co-formulated
Bictegravir, Emtricitabine, and Tenofovir Alafenamide versus Co-formulated
Abacavir, Dolutegravir, and Lamivudine.
AB - BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended for
first-line antiretroviral therapy in combination with two nucleos(t)ide reverse
transcriptase inhibitors. Co-formulated bictegravir, emtricitabine, and tenofovir
alafenamide (B/F/TAF), a novel, INSTI-based regimen, is currently approved in the
US and EU for the treatment of HIV-1 infection and recommended as first-line
treatment in current guidelines. In our current analysis, we aimed to determine
changes in patient-reported symptoms over time among HIV-1-infected adults who
initiated or switched to B/F/TAF versus another INSTI-based regimen, co
formulated abacavir, dolutegravir, and lamivudine (ABC/DTG/3TC). METHODS: A
planned secondary analysis of patient-reported outcomes was conducted for two
double-blind, randomized, phase III studies in HIV-1-infected adults comparing
B/F/TAF with ABC/DTG/3TC: one in treatment-naive individuals (GS-US-380-1489,
ClinicalTrials.gov NCT02607930) and the other in virologically suppressed
participants (GS-US-380-1844, ClinicalTrials.gov NCT02603120). In both studies,
the HIV symptoms distress module (HIV-SI) was administered at baseline (BL) and
weeks 4, 12, and 48. Responses to each of the 20 items were dichotomized as
bothersome or not bothersome. Treatment differences were assessed using
unadjusted and adjusted logistic regression models (adjusted for BL HIV-SI count,
age, sex, BL Veterans Aging Cohort Study [VACS] Index, medical history of serious
mental illness, BL Short Form [SF]-36 Physical Component Summary [PCS], BL SF-36
Mental Component Summary [MCS], and, for virologically suppressed participants
only, years since HIV diagnosis). We conducted longitudinal modeling of
bothersome symptoms using a generalized mixed model including treatment, time,
time-by-treatment, and additional covariates from the adjusted logistic
regression model as described above. The Pittsburgh Sleep Quality Index (PSQI)
was administered at the same frequency as the HIV-SI, and the total score was
dichotomized as good or poor sleep quality. Similar models to those used for HIV
SI were applied, using BL sleep quality and BL SF-36 MCS as covariates.
Statistical significance was assessed using p < 0.05. RESULTS: Across both
studies, bothersome symptoms were reported by fewer participants on B/F/TAF than
those on ABC/DTG/3TC. In treatment-naive adults, fatigue/loss of energy,
nausea/vomiting, dizzy/lightheadedness, and difficulty sleeping were reported
significantly less with B/F/TAF at two or more time points. Fatigue and nausea
were also significantly less common for those receiving B/F/TAF in longitudinal
models. In virologically suppressed participants, nausea/vomiting,
sad/down/depressed, nervous/anxious, and poor sleep quality (from the PSQI) were
reported significantly less with B/F/TAF at two or more time points, as well as
in longitudinal models. CONCLUSIONS: B/F/TAF was associated with lower prevalence
of bothersome symptoms than ABC/DTG/3TC in both treatment-naive and virologically
suppressed adults.
PMID- 29956090
TI - Present status and future of ultrasonic quantitative diagnostic techniques.
PMID- 29956088
TI - Postmortem Brain, Cerebrospinal Fluid, and Blood Neurotrophic Factor Levels in
Alzheimer's Disease: A Systematic Review and Meta-Analysis.
AB - Accumulating evidence suggest that aberrations of neurotrophic factors are
involved in the etiology and pathogenesis of Alzheimer's disease (AD), but
clinical data were inconsistent. Therefore, a meta-analysis on neurotrophic
factor levels in AD is necessary. We performed a systematic review of blood, CSF,
and post-mortem brain neurotrophic factor levels in patients with AD compared
with controls and quantitatively summarized the clinical data in blood and CSF
with a meta-analytical technique. A systematic search of PubMed and Web of
Science identified 98 articles in this study (with samples more than 9000).
Random effects meta-analysis demonstrated that peripheral blood BDNF levels were
significantly decreased in AD patients compared with controls. However, blood
NGF, IGF, and VEGF did not show significant differences between cases and
controls. In CSF, random effects meta-analysis showed significantly deceased BDNF
and increased NGF levels in patients with AD, whereas IGF and VEGF did not show
significant differences between the AD group and control group. In addition, 23
post-mortem studies were included in the systematic review. Although data from
post-mortem brains were not always consistent across studies, most studies
suggested decreased BDNF and increased (pro)NGF levels in hippocampus and
neocortex of patients with AD. These results provide strong clinical evidence
that AD is accompanied by an aberrant neurotrophin profile, and future
investigations into neurotrophins as biomarkers (especially CSF BDNF and NGF) and
therapeutic targets for AD may be warranted.
PMID- 29956089
TI - Nesfatin-1 Improve Spatial Memory Impairment Following Transient Global Cerebral
Ischemia/Reperfusion via Inhibiting Microglial and Caspase-3 Activation.
AB - Nesfatin-1, a recently discovered peptide, is involved in important functions
such as food intake regulation and energy homeostasis. Previous studies have
demonstrated that it has protective effects following myocardial injury and also
protects dopaminergic cells against neurotoxicity with the anti-inflammatory and
anti-apoptotic mechanisms. In this study, we aimed to assay the neuroprotective
effects of Nesfatin-1 after brain ischemia/reperfusion. Twenty-eight male Wistar
rats were randomly selected and allocated in the form of four groups (sham,
Nesfatin-1, ischemia, ischemia+Nesfatin-1). Ischemia was created by obstruction
couple common carotid arteries in 20-min period. Saline as a vehicle and Nesfatin
1 (20 MUg/kg, intraperitoneally) were injected at the time of reperfusion.
Spatial memory performances were evaluated by the Morris water maze. The level of
protein expression was determined by immunohistochemical and immunofluorescence
staining. Nesfatin-1 significantly reduced caspase-3 (P < 0.01) and microglial
activation (P < 0.01) and improved spatial memory impairments (P < 0.05) induced
by brain ischemia. Nesfatin-1 has significant neuroprotective effects and can be
introduced as a therapeutic agent against cerebral ischemia-induced injuries.
PMID- 29956091
TI - Breast Cancer Litigation in the 21st Century.
AB - BACKGROUND: Approximately 15% of general surgeons practicing in the United States
face a medical malpractice lawsuit each year. This study aimed to determine the
reasons for litigation for breast cancer care during the past 17 years by
reviewing a public legal database. METHODS: The LexisNexis legal database was
queried using a comprehensive list of terms related to breast cancer, identifying
all cases from 2000 to 2017. Data were abstracted, and descriptive analyses were
performed. RESULTS: The study identified 264 cases of litigation pertaining to
breast cancer care. Delay in breast cancer diagnosis was the most common reason
for litigation (n = 156, 59.1%), followed by improperly performed procedures (n =
26, 9.8%). The medical specialties most frequently named in lawsuits as primary
defendants were radiology (n = 76, 28.8%), general surgery (n = 74, 28%), and
primary care (n = 52, 19.7%). The verdict favored the defendant in 145 cases
(54.9%) and the plantiff in 60 cases (22.7%). In 59 cases (22.3%), a settlement
was reached out of court. The median plaintiff verdict payouts ($1,485,000) were
greater than the settlement payouts ($862,500) (p = 0.04). CONCLUSION: Failure to
diagnose breast cancer in a timely manner was the most common reason for
litigation related to breast cancer care in the United States. General surgery
was the second most common specialty named in the malpractice cases studied. Most
cases were decided in favor of the defendant, but when the plaintiff received a
payout, the amount often was substantial. Identifying the most common reasons for
litigation may help decrease this rate and improve the patient experience.
PMID- 29956092
TI - Regional Variation in Performance for Commission on Cancer Breast Quality
Measures and Impact on Overall Survival.
AB - BACKGROUND: Adherence to quality measures has become an important indicator of
cancer center performance for high-quality cancer care. We examined regional
variation in performance for Commission on Cancer breast quality measures and its
impact on overall survival (OS) for those measures that have been shown to impact
OS. METHODS: Six breast quality measures were analyzed using the National Cancer
Data Base from 2014 to 2015, and a multivariable model was used to assess
performance for each measure by region. Kaplan-Meier and Cox proportional hazard
models were used to examine OS between high- and low-performing centers from 2007
to 2012. RESULTS: Overall, 305,391 women had surgery at 1322 institutions in nine
US regions; 90.8% underwent needle biopsy (range 86.0-92.6% between regions, p <
0.01), 69.8% had breast-conserving surgery (BCS) for stage 0-II cancer (60.9
79.3%, p < 0.01), 85.2% aged < 70 years had radiation therapy (RT) after BCS
(79.6-90.8%, p < 0.01), 78.3% of women with four or more positive nodes had post
mastectomy RT (70.9-84.5%, p < 0.01), 90.9% with hormone receptor (HR)-positive
stage IB-III cancer had hormone therapy (83.7-95.1%, p < 0.01), and 89.4% aged <
70 years with HR-negative stage IB-III cancer had chemotherapy (87.6-91.4%, p <
0.01). Multivariate analyses adjusted for patient and facility factors found that
region was the only consistent predictor of non-compliance across measures. With
median 65-month follow-up, there was no difference in OS between high- and low
performing centers for the three measures that have been shown to impact OS.
CONCLUSIONS: There is significant regional variation in performance on the breast
quality measures but this variation did not impact OS. Targeted efforts in
certain areas of the country may help improve performance on these measures.
PMID- 29956093
TI - Intraoperative Injection of 99m-Tc Sulfur Colloid for Sentinel Lymph Node Biopsy:
Can the Preoperative Injection Procedure be Eliminated?
AB - BACKGROUND: Sentinel lymph node biopsy (SLNB) historically involves a separate
appointment in the Radiology Department to undergo injection of the radiocolloid
tracer (RT) the day of, or prior to, surgery, which can lead to disruptions in
scheduling. Furthermore, the patient must endure an additional procedure. In a
pilot study, intraoperative injection of the RT was previously shown to be
equally as effective as preoperative injection. This study evaluates the efficacy
of this method in a large cohort and examines factors associated with failure of
the RT to reach the axilla. METHODS: A retrospective review of patients who
underwent SLNB between June 2010 and June 2017 was performed. All patients were
injected immediately following intubation with sulfur colloid and blue dye,
unless contraindicated. Operative records were reviewed to determine whether
sentinel nodes were identified and if gamma counts were detected. Patient and
tumor characteristics were examined to identify factors related to failed RT
uptake in the axilla. RESULTS: In 7 years, 453 SLNBs were performed, with
sentinel nodes being detected in 447 (98.7%) of these SLNBs. In the six cases
where no nodes were detected, all had a prior ipsilateral axillary procedure.
Sentinel nodes were undetectable with the gamma probe in 16 (3.5%) cases; a prior
axillary procedure was the only statistically significant independent variable
associated with this failure. CONCLUSION: Intraoperative injection of the RT is
highly effective in the detection of sentinel nodes in clinically node-negative
breast cancer patients. Eliminating the need for a preoperative injection of RT
can avoid scheduling conflicts and decrease patient morbidity.
PMID- 29956094
TI - Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers.
AB - BACKGROUND: Molecular alterations impact tumor prognosis and response to
treatment. This study was designed to identify transcriptomic and epigenomic
signatures of breast cancer (BC) tumors from patients with any prior malignancy.
METHODS: RNA-sequencing and genome-wide DNA methylation profiles from BCs were
generated in the Cancer Genome Atlas project. Patients with secondary breast
cancer (SBC) were separated by histological subtype and matched to primary breast
cancer controls to create two independent cohorts of invasive ductal (IDC, n =
36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes,
as well as differentially methylated genomic regions, were integrated to identify
epigenetically regulated abnormal gene pathways in SBCs. RESULTS: Differentially
expressed genes were identified in IDC SBCs (n = 727) and in ILC SBCs (n = 261;
Wilcoxon's test; P < 0.05). In IDC SBCs, 105 genes were upregulated and
hypomethylated, including an estrogen receptor gene, and 73 genes were
downregulated and hypermethylated, including genes involved in antigen
presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC
SBCs, however, only 17 genes were synchronously hypomethylated and upregulated,
whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene
expression signatures closely corresponded with each histological subtype with
only 1.51% of genes overlapping between the two histological subtypes.
CONCLUSIONS: Differential gene expression and DNA methylation signatures are seen
in both IDC and ILC SBCs, including genes that are relevant to tumor growth and
proliferation. Differences in gene expression signatures corresponding with each
histological subtype emphasize the importance of disease subtype-specific
evaluations of molecular alterations.
PMID- 29956095
TI - Predicting Non-sentinel Lymph Node Metastases in Patients with a Positive
Sentinel Lymph Node After Neoadjuvant Chemotherapy.
AB - BACKGROUND: The standard of care for breast cancer patients treated with
neoadjuvant chemotherapy (NAC) who have a positive sentinel lymph node (+SLN)
after NAC is completion axillary lymph node dissection (ALND). This study aimed
to develop a nomogram to predict additional nodal disease in patients with +SLN
after NAC. METHODS: The study reviewed patients 18 years of age or older who had
invasive breast cancer treated with NAC followed by SLN surgery with +SLN and
ALND between 2006 and 2017 at the authors' institution. Factors predictive of
positive non-SLNs were analyzed using uni- and multivariable logistic regression.
RESULTS: The study identified 120 patients with +SLN after NAC and ALND. Of these
patients, 30.8% were clinically node-negative (cN-), and 69.2% were clinically
node-positive (cN+) before NAC. Tumor biology was human epidermal growth factor
receptor 2-positive (HER2+) for 20%, hormone receptor-positive (HR+)/HER2- for
66.7%, and triple-negative breast cancer (TNBC) for 13.3% of the patients.
Additional nodal disease was found on ALND for 63.3% of the patients. In the
univariate analysis, the factors predictive of positive non-SLNs were biologic
subtype (TNBC and HR+/HER2- vs HER2+; p < 0.001), higher grade (p = 0.047),
higher pT category (p = 0.02), SLN extranodal extension (p = 0.03), larger SLN
metastasis size (p < 0.001), and higher number of +SLNs (p = 0.02). The factors
significant in the multivariable analysis included number of +SLNs, grade 3 vs
grade 1 or 2, HER2+ versus HER2-, cN+ versus cN-, and larger SLN metastasis size.
The resulting model showed excellent discrimination (area under the curve, 0.82;
95% confidence interval, 0.74-0.90) and good calibration (p = 0.54, Hosmer
Lemeshow). CONCLUSION: A clinical prediction model incorporating biologic
subtype, grade, clinical node status, size of the largest SLN metastasis, and
number of +SLNs can help physicians and patients estimate the likelihood of
additional nodal disease and may be useful for guiding decision making regarding
axillary management.
PMID- 29956097
TI - Correction to: Backbone and side-chain chemical shift assignments of the kringle
domain of human receptor tyrosine kinase-like orphan receptor 1 (ROR1).
AB - The authors would like to include an additional institution to their affiliation
which was initially not included in the original publication of the article.
PMID- 29956096
TI - A case of a maintenance hemodialysis patient with autosomal dominant polycystic
kidney disease who underwent living donor liver transplantation alone due to
refractory liver cyst infection.
AB - Liver cysts are observed in 83% of cases of autosomal dominant polycystic kidney
disease (ADPKD). Although not as prevalent as renal cyst infection, liver cyst
infection is a serious complication that is sometimes difficult to treat. We
report the case of a maintenance hemodialysis patient with ADPKD who received a
living donor liver transplantation alone (LDLTA) due to refractory liver cyst
infection. The patient was a 67-year-old Japanese man who developed fever and
right-side abdominal pain, and liver cyst infection was suspected. Treatment with
multiple antibiotics was ineffective. Many liver cysts were observed on magnetic
resonance imaging scans and a cyst in liver segment S6, which produced the
strongest signal variation, was drained. The fever subsided temporarily, but
multiple infected liver cysts were observed on follow-up imaging examination; 4
months later, hepatectomy and LDLTA were performed. Although LDLTA due to
refractory liver cyst infection in maintenance hemodialysis patients with ADPKD
is risky and should be carefully considered, it may be the only effective
treatment.
PMID- 29956098
TI - Is the prevalence of orthorexia nervosa in an Australian university population
6.5%?
AB - PURPOSE: To survey Australian adults at a Sydney university about: their
tendencies towards the proposed health food eating disorder, orthorexia nervosa
(and to estimate the prevalence of this condition), their eating behaviours, and
their body image. METHODS: A pilot, cross-sectional and descriptive online survey
was conducted on staff and students at the University of New South Wales, Sydney.
The primary outcome was the score on the most commonly used and validated measure
of orthorexic behaviours, the ORTO-15. The point prevalence of orthorexia nervosa
was estimated using the ORTO-15 cut-off score of < 35. Other outcomes were the
Eating Attitudes Test-26 and the Body Shape Questionnaire-34. RESULTS: In the
sample of 92 Australian adults recruited at a university, there was a point
prevalence rate for orthorexia nervosa of 21% when using the ORTO-15 cut-off
value of < 35. If criteria A and B of proposed diagnostic criteria for the
condition were also taken into consideration (i.e. someone with orthorexia
nervosa would display disordered healthy eating tendencies; as well as were:
underweight, or had marked concern with their body shape, or had significant
impairment of functioning in work life or social life), the true prevalence rate
could be considered to be 6.5%. CONCLUSIONS: Using the ORTO-15 tool alone may
overestimate the true prevalence of orthorexia nervosa. Further research into the
accurate diagnosis and treatment of orthorexia nervosa is needed. LEVEL OF
EVIDENCE: Level V, descriptive study.
PMID- 29956099
TI - Relationship of para- and perirenal fat and epicardial fat with metabolic
parameters in overweight and obese subjects.
AB - BACKGROUND: The accumulation of visceral body fat, has been shown to be
associated with higher risk of metabolic and cardiovascular disease. This study
was addressed to examine whether para- and perirenal fat thickness and epicardial
fat thickness were correlated with anthropometric- and cardiometabolic risk
factors. METHODS: A cohort of 102 uncomplicated overweight and obese patients was
examined. BMI, waist circumference, blood pressure, fasting insulin, glucose,
triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol serum levels,
and insulin resistance (assessed by HOMAIR) were measured. Para- and perirenal
fat thickness (PUFT) and epicardial fat thickness (EUFT) were measured by
ultrasounds. RESULTS: PUFT was positively correlated with BMI (p < 0.001), waist
circumference (p < 0.001), insulin (p < 0.001), HOMAIR (p < 0.001), triglycerides
(p < 0.05), systolic (p < 0.05) and diastolic (p < 0.05) blood pressure, and
negatively correlated with HDL-cholesterol (p < 0.01). EUFT was positively
associated with age (p < 0.01), BMI (p < 0.001), waist circumference (p < 0.001),
systolic (p < 0.01) and diastolic (p < 0.001) blood pressure, and LDL-cholesterol
(p < 0.05). A multivariate analysis by multiple linear regression was performed,
and the final model showed a direct association of waist circumference with both
PUFT and EUFT, a correlation of PUFT with HOMAIR (positive) and HDL-cholesterol
(negative), and a direct association of EUFT (both long axis and short axis) with
LDL-cholesterol. All these correlations were independent of other anthropometric,
metabolic and hemodynamic parameters. CONCLUSIONS: This study shows that
accumulation of central fat in apparently healthy overweight and obese subjects
is associated to a simultaneous increase of pararenal, perirenal and epicardial
fat. Moreover, it shows that only para- and perirenal fat is independently
associated to insulin resistance and lower HDL-cholesterol, and only epicardial
fat is independently associated to higher LDL cholesterol. Level of evidence
Level V, cross-sectional descriptive study.
PMID- 29956101
TI - Understanding the Delusion of Theft.
AB - The elderly with dementing illness often present with psychotic symptoms such as
delusions, but the thematic content of delusions in the elderly differs from that
of delusions expressed by younger individuals, and can be pathognomonic of early
dementia. The aim of this paper is to review the recent literature on the
delusion of theft, the most prevalent delusion in the elderly, in order to arrive
at a deeper understanding of its sources and to identify successful therapeutic
approaches. The literature from 2000 to the present was searched on the Google
Scholar database using relevant search terms. Several older classical papers were
also referenced. Understanding the origins of the delusion of theft - multiple
losses, attempts at attributing such losses to an outside source, attempts at
reliving a happier past - helps in devising responses that are comforting to the
patient. The distress that often accompanies the delusion of having been robbed
can be decreased by nursing home improvements in the handling of personal
possessions, by the correction of sensory deficits, and by the provision of
activities that distract from loneliness. Attention to stimuli that trigger the
delusion helps to limit its occurrence. Medications may help, but can sometimes
make matters worse. Understanding that delusional thinking can arise from sensory
and cognitive deficits is critical to empathic caregiving and also to the
lessening of caregiver burden.
PMID- 29956100
TI - Cardiac and skeletal muscle effects of electrical weapons : A review of human and
animal studies.
AB - Conducted Electrical Weapons (CEWs) are being used as the preferred non-lethal
force option for police and special forces worldwide. This new technology
challenges an exposed opponent similarly to the way they would be challenged by
physical exercise combined with emotional stress. While adrenergic and metabolic
effects have been meta-analyzed and reviewed, there has been no systematic review
of the effects of CEWs on skeletal and cardiac muscle. A systematic and careful
search of the MedLine database was performed to find publications describing
pathophysiological cardiac and skeletal muscle effects of CEWs. For skeletal
muscle effects, we analyzed all publications providing changes in creatine
kinase, myoglobin and potassium. For cardiac effects, we analyzed reported
troponin changes and arrhythmias related to short dart-to-heart-distances.
Conducted electrical weapons satisfy all relevant electrical safety standards and
there are, to date, no proven electrocution incidents caused by CEWs. A potential
cardiovascular risk has been recognized by some of the experimental animal data.
The effects on the heart appear to be limited to instances when there is a short
dart-to-heart-distance. The effect on the skeletal muscle system appears to be
negligible. A responsible use of a CEW on a healthy adult, within the guidelines
proposed by the manufacturer, does not imply a significant health risk for that
healthy adult.
PMID- 29956102
TI - Abnormal dynamics of functional connectivity density in children with benign
epilepsy with centrotemporal spikes.
AB - Converging evidence has shown the link between benign epilepsy with
centrotemporal spikes (BECTS) and abnormal functional connectivity among distant
brain regions. However, prior research in BECTS has not examined the dynamic
changes in functional connectivity as networks form. We combined functional
connectivity density (FCD) mapping and sliding windows correlation analyses, to
fully capture the functional dynamics in patients with respect to the presence of
interictal epileptic discharges (IEDs). Resting-state fMRI was performed in 43
BECTS patients and 28 healthy controls (HC). Patients were further classified
into two subgroups, namely, IED (n = 20) and non-IED (n = 23) depending on the
simultaneous EEG-fMRI recordings. The global dynamic FCD (dFCD) was measured
using sliding window correlation. Then we quantified dFCD variability using their
standard deviation. Compared with HC, patients with and without IEDs both showed
invariable dFCD (decreased) among the orbital fontal cortex, anterior cingulate
cortex and striatum, as well as variable dFCD (increased) in the posterior
default mode network (P < 0.05, AlphaSim corrected). Correlation analysis
indicated that the variable dFCD in precuneus was related to seizure onset age (P
< 0.05, uncorrected). BECTS with IEDs showed variable dFCD in regions related to
the typical seizure semiology. The abnormal patterns of fluctuating FCD in BECTS
suggest that both active and chronic epileptic state may contribute to altered
dynamics of functional connectivity associated with cognitive disturbances and
developmental alterations. These findings highlight the importance of considering
fluctuating dynamic neural communication among brain systems to deepen our
understanding of epilepsy diseases.
PMID- 29956103
TI - Patient experience with upper airway stimulation in the treatment of obstructive
sleep apnea.
AB - OBJECTIVE: Selective upper airway stimulation (sUAS) is a new treatment modality
for patients with obstructive sleep apnea (OSA) and continuous positive airway
pressure (CPAP) failure. The aim of this study was to analyze therapy adherence
and to structure patient experience reports. METHODS: Patients from two German
implantation centers were included. Besides demographic and OSA characteristics
of that cohort, patients answered a questionnaire on subjective sensation of the
stimulation, use of different functions, side effects, and an inventory for the
description of the attitude towards sUAS. The use of the sUAS was evaluated as a
read-out of the implanted system. RESULTS: The overall apnea-hypopnea-index (AHI)
of that 102 assessed patients reduced from initially 32.8/h to 12.6/h at the last
available assessment. The responder rate was 75%. There was an objective therapy
usage of 5.7 h and subjective reports of 6.8 nights per week. The attitude
resulted in strong agreement towards the statement "UAS reduces the problems
caused by my sleep apnea". Information on sensing the stimulation and usage
habits could be gathered such as that stimulation is only sensed by 67.9% of the
patients upon waking in the morning and that 73.6% of the patients do not change
the voltage in general. CONCLUSION: This investigation on the sUAS therapy
revealed a high adherence to the therapy. The AHI or daytime sleepiness do not
have obvious influence on adherence. Patients expressed a positive attitude
towards sUAS. These patient reports upon stimulation experiences are of great
help to consult candidates for sUAS in future.
PMID- 29956104
TI - Improved follow-up by peripheral arterial tonometry in CPAP-treated patients with
obstructive sleep apnea and persistent excessive daytime sleepiness.
AB - BACKGROUND: OSA-patients with persistent excessive daytime sleepiness (EDS)
despite CPAP treatment are challenging in daily clinical life. To rule out
residual sleep-disordered breathing (SDB), CPAP device-derived data are used in
outpatient setting. In case of no pathological finding, a more intensive work-up
with is necessary. 6-channel portable monitoring (6Ch-PM) is frequently used to
exclude residual SDB. Peripheral arterial tonometry (PAT), as embodied in the
WatchPAT device, represents an alternative technique for detecting SDB based on
changes in autonomic tone. We wanted to investigate whether PAT might be a useful
tool to improve diagnostic work-up in this specific patient group by better
identifying residual SDB due to insufficient CPAP-adjustment. METHODS: Forty-nine
OSA patients (39 male, 10 female) with sufficient CPAP treatment according to
device-derived data were consecutively recruited. EDS was assessed by Epworth
Sleepiness Scale (ESS). All patients underwent home-based CPAP therapy control by
6Ch-PM and portable monitoring using PAT technology on two consecutive nights. A
sequence of both types of monitoring was randomized to prevent possible first
night effect bias. RESULTS: Twelve out of 49 patients showed persistent EDS
according to ESS (ESS > 10 points). 6Ch-PM showed a residually increased AHI
under CPAP-treatment in 2 of those 12 subjects (positive predictive value, PPV =
16.7%). PAT-PM revealed 5 patients of those 12 with residual SDB (PPV = 41.7%).
CONCLUSION: PAT could detect significantly more residual SDB under CPAP treatment
than 6Ch-PM. Diagnostic work-up of CPAP-treated OSA patients with persistent EDS
might be optimized, as insufficient pressure level adjustments could be
recognized more precisely in time, possibly preventing more resource-consuming
procedures, and potentially increased morbidity. CLINICAL TRIAL REGISTRATION:
DRKS00007705.
PMID- 29956106
TI - Loss and Regain of Weight After Laparoscopic Sleeve Gastrectomy According to
Preoperative BMI : Late Results of a Prospective Study (78-138 months) with 93%
of Follow-Up.
AB - INTRODUCTION: The long-term results in sleeve gastrectomy (SG) have been reported
in few publications. None of them has evaluated the importance of preoperative
BMI (kg/m2) in the final results. OBJECTIVE: To determine the loss and regain of
weight after SG, determining the influence of preoperative BMI in final results.
MATERIAL AND METHODS: This prospective study included all patients operated
between 2006 and 2010. Exclusion criteria corresponded to patients with Barrett's
esophagus, type 2 diabetes, and hiatal hernia greater than 3 cm. Patients were
followed and controlled "face to face" by the main author. RESULTS: From 109
original patients included in this study, 102 (93.5%) completed the late follow
up. Patients were divided into four groups: (a) I-29 patients with BMI 32.1-34.9;
(b) II-56 patients with BMI 35-39.9; (c) III-20 patients with BMI 40-49.9; and
(d) IV-4 patients with BMI > 50. There was a significant decrease in the BMI 12
to 24 months after surgery. At the late control, patients in groups III and IV
regained weight in 85 and 100%, respectively. Patients in groups I and II had 3.6
and 38% of weight regain. CONCLUSION: The changes in weight after SG are directly
related to preoperative BMI: the higher this value, the higher the percentage of
failure and weight regain late after surgery. Besides, laparoscopic SG seems to
be an adequate operation at late control in terms of loose of weight after
surgery in patients with a BMI less than 40 kg/m2 before surgery.
PMID- 29956107
TI - Initial Assessment of Mucosal Capture and Leak Pressure After Gastrointestinal
Stapling in a Porcine Model.
AB - BACKGROUND: Anastomotic leak is a leading cause of morbidity and mortality in
gastrointestinal surgery. The serosal aspect of staple lines is commonly observed
for integrity, but the mucosal surface and state of mucosa after firing is less
often inspected. We sought to assess the degree of mucosal capture when using
stapling devices and determine whether incomplete capture influences staple line
integrity. METHODS: Porcine ileum was transected in vivo and staple lines were
collected and rated for degree of mucosal capture on a 5-point scale from 1
(mucosa mainly captured on both sides) to 5 (majority of mucosa not captured).
Mucosal capture was also assessed in ex vivo staple lines, and fluid leakage
pressure and location of first leak was assessed. Stapling devices studied were
Echelon Flex GST with 60-mm blue (GST60B) and green (GST60G) cartridges, and
Medtronic EndoGIA Universal with Tri-Staple TechnologyTM with 60 mm medium
(EGIA60AMT) reloads (purple). RESULTS: GST60B and GST60G staple lines produced
significantly better mucosal capture scores than the EGIA60AMT staple lines (p <
0.001, in all tests). Compared to EGIA60AMT, leak pressures were 39% higher for
GST60B (p < 0.001) and 23% higher for GST60G (p = 0.022). Initial staple line
leak site was associated with incomplete mucosal capture 78% of the time.
CONCLUSIONS: There are differences in degree of mucosal capture between
commercial staplers, and the devices that produce better mucosal capture had
significantly higher leak pressures. Further research is needed to determine the
significance of these findings on staple line healing throughout the
postoperative period.
PMID- 29956105
TI - Clinical Research on Alzheimer's Disease: Progress and Perspectives.
AB - Alzheimer's disease (AD), the most common type of dementia, is becoming a major
challenge for global health and social care. However, the current understanding
of AD pathogenesis is limited, and no early diagnosis and disease-modifying
therapy are currently available. During the past year, significant progress has
been made in clinical research on the diagnosis, prevention, and treatment of AD.
In this review, we summarize the latest achievements, including diagnostic
biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials
targeting amyloid-beta (Abeta), tau, and neurotransmitters, early intervention,
and primary prevention and systemic intervention approaches, and provide novel
perspectives for further efforts to understand and cure the disease.
PMID- 29956108
TI - Does Bismuth Subgallate Affect Smell and Stool Character? A Randomized Double
Blinded Placebo-Controlled Trial of Bismuth Subgallate on Loop Duodenal Switch
Patients with Complaints of Smelly Stools and Diarrhea.
AB - BACKGROUND: Loop duodenal switch (LDS) can result in fat and starch
malabsorption. In a small percentage of patients, a relevant qualitative and
quantitative change in stools happens usually characterized by steatorrhea-like
diarrhea. Bismuth subgallate (BS) has been marketed as a way to eliminate the
odor associated with flatulence and bowel movements. The objective of this study
is to see the efficacy and effect of BS on the quality of life (QOL) in patients
undergoing LDS. METHODS: A prospective, randomized, double-blinded, placebo
controlled, crossover study was designed. Thirty-six patients who reported flatus
and/or stool odor changes and have completed at least 6 months post-LDS were
included. Patients participated in two treatment periods, each lasting for 1
week, separated by 1-week washout. Patients received 200 mg BS, 2 capsules per
meal, or placebo for 1 week each. The Gastrointestinal Quality of Life Index
(GIQLI) questionnaire was used to compare the QOL before the initiation of the
therapy and after each treatment completion. RESULTS: Of 36 patients, 5 patients
were lost to follow-up and 2 were withdrawn from the study. And 29 patients were
included for final analysis. GIQLI scores obtained with BS treatment completion
were significantly higher both overall (P = 0.007) and in the digestive domain (P
< 0.001) than those obtained before the treatment. GIQLI scores obtained from the
other domains were also higher compared to the pre-treatment as well as placebo
treatment but not statistically significant. CONCLUSION: In our double-blinded
trial, treatment with BS after LDS statistically improves GIQLI score and
steatorrhea-like symptoms.
PMID- 29956109
TI - Consequences of different types of informal caregiving for mental, self-rated,
and physical health: longitudinal findings from the German Ageing Survey.
AB - PURPOSE: This study aims at extending current knowledge on consequences of
informal caregiving by analyzing the influence of different caregiving types on
mental, physical, and self-rated health longitudinally. METHODS: Data from wave
2008, 2011, and 2014 of the nationally representative German Ageing Survey were
used, drawing on 16,412 observations aged 40-95 years in fixed effects (FE)
regression analyses. Three informal caregiving types (helping around the house,
looking after someone, nursing care services), which we used as explanatory
variables and four health outcomes (depressive symptoms, self-rated health,
pulmonary function, and morbidity), were assessed with structured interviews and
written questionnaires. FE regression analysis was used for our calculations.
RESULTS: Results revealed that none of the caregiving types was significantly
associated with pulmonary function or morbidity. However, helping around the
house and looking after someone were significantly associated with increased
depressive symptoms. Additionally, all three types of informal caregiving were
significantly associated with decreased self-rated health. CONCLUSION: The
results of this study indicate that the impact of care on health differs. First,
it differs in dependence on the health outcome focused; only mental and self
rated health are negatively associated with care. Second, the impact depends on
the caregiving type performed. This knowledge might help to develop support
options which are specific to the caregiving type and the health aspects in order
to reduce negative health consequences.
PMID- 29956110
TI - Maltodextrin and Gum Arabic-Based Microencapsulation Methods for Anthocyanin
Preservation in Jucara Palm (Euterpe edulis Martius) Fruit Pulp.
AB - The jucara fruits (Euterpe edulis Martius), native to the Atlantic Forest, are
rich in anthocyanins. To preserve the anthocyanins in jucara fruit pulp, this
study aimed to evaluate the effectiveness of microencapsulation by spray drying
and freeze drying with maltodextrin (dextrose equivalent 16.5 to 19.5) and gum
arabic in different proportions. The obtained microparticles were characterized
by quantifying the total polyphenol and anthocyanin contents, by performing
differential scanning calorimetry, thermogravimetry, and infrared spectroscopy
and by using scanning electron microscopy to analyze the morphology of the
particles. The total amount of polyphenols in the fruit pulp was 750 +/- 16.7 mg
GAE/100 g of the freeze-dried sample. The total anthocyanins in the fruit pulp
was 181.25 +/- 5.36 (mg/100 g). The microparticles were formed by employing
maltodextrin and gum arabic in a 1:1 proportion as the polymeric matrix; the
mixtures of pulp and polymeric matrix were prepared in proportions of 2:3 and
2:1, preserving up to 83.69% of the anthocyanin content. Lyophilization of the
2:1 mixture resulted in an anthocyanin content of 116.89 +/- 4.43 (mg/100 g),
whereas lyophilization of the 2:3 mixture resulted in 151.68 +/- 1.39 (mg/100 g)
anthocyanin content, which did not differ from the value obtained by spray drying
the 2:3 mixture (150.76 +/- 5.79 (mg/100 g)). Thermal analyses showed that the
microparticles obtained by freeze drying at a ratio of 2:3 presented greater
resistance to degradation with increasing temperature. The incorporation of the
pulp in the polymeric matrix was demonstrated by IR analyses. Microparticles
obtained by freeze drying showed the formation of various-sized flakes, whereas
those obtained by spray drying were spherical in shape. Microencapsulation is a
possible alternative for improving the stability of the anthocyanins in this
fruit.
PMID- 29956111
TI - Ferrari Corporate Wellness Program: Results of a Pilot Analysis and the "Drag"
Impact in the Workplace.
AB - INTRODUCTION: Preventive strategies based on advice and interventions on
lifestyle habits represent the most powerful resource available to reduce the
burden of cardiovascular (CV) diseases. Workplace represents an unmissable
context for lifestyle changes at population level. AIM: To evaluate the mid-term
efficacy of a corporate wellness program in a cohort of healthy and physically
active employees of the Ferrari car manufacturer. METHODS: A corporate wellness
program, named "Ferrari Formula Benessere", was proposed to adult individuals
working in a Ferrari car company at Maranello, Modena (Italy). Employees who
voluntarily agreed to the program received healthy nutritional advice and were
trained three times a week (60 min per session), and periodically re-evaluated
during a 4-year follow-up period. RESULTS: Among the 719 Ferrari employees that
joined the program, 168 (23%) subjects (88.5% males, age 30.8 +/- 5.9 years) were
considered the most active participants, based on a self-administered
standardized questionnaire, and included in the study. A relevant improvement of
several CV risk factors (body mass index, total and LDL cholesterol,
triglycerides, blood pressure) and cardio-respiratory fitness parameters
(estimated VO2max, Wattpeak, METs) was observed compared to baseline values.
Furthermore, it was recorded a clear "drag effect" towards non-participating and
sedentary peers, resulting in a 90% adherence increase over the years.
CONCLUSIONS: The "Ferrari Formula Benessere" corporate wellness project proved to
be effective in improving CV risk profile and cardio-respiratory fitness in a
population of already physically active employees.
PMID- 29956112
TI - Prevalence and Clinical Correlates of Left Ventricular Hypertrophy in Black
Africans.
AB - INTRODUCTION: African-Americans present higher prevalence of left ventricular
hypertrophy (LVH) when compared with white populations. However, there is a lack
of information about the prevalence and determinants of LVH in black individuals
living in Africa. METHODS: A cross-sectional study was performed with a non
probabilistic sample comprised of 609 University workers from Angola/Africa,
describing the prevalence of LVH and the determinants of left ventricular mass.
Echocardiographic measurements were performed and left ventricular mass was
indexed to body surface area. Systolic and diastolic blood pressures were
measured, along with anthropometric and clinical variables. RESULTS: Chamber
diameter and wall thickness were higher in men compared to women. Additionally,
LVM was higher in men (114.2 +/- 36 vs 98.4 +/- 31.9, P < 0.001), and the overall
prevalence of LVH in black Angolans was 41.1%, which tended to be higher in women
(44.5 vs 37.4%, P = 0.096). In men, systolic blood pressure and BMI were
independently associated with LVM, while age, systolic blood pressure and waist
circumference were associated with LVM in women. CONCLUSIONS: In summary, blood
pressure levels were the main determinants of LVH in black Africans, although
different anthropometric variables showed mild influence in LVM. Our data
suggests that LVH prevalence and determinants in black Africans are similar to
that reported for African-Americans.
PMID- 29956113
TI - Expansion and diversification of the gibberellin receptor GIBBERELLIN INSENSITIVE
DWARF1 (GID1) family in land plants.
AB - KEY MESSAGE: Here we uncover the major evolutionary events shaping the evolution
of the GID1 family of gibberellin receptors in land plants at the sequence,
structure and gene expression levels. Gibberellic acid (gibberellin, GA) controls
key developmental processes in the life cycle of land plants. By interacting with
the GIBBERELLIN INSENSITIVE DWARF1 (GID1) receptor, GA regulates the expression
of a wide range of genes through different pathways. Here we report the
systematic identification and classification of GID1s in 54 plants genomes,
encompassing from bryophytes and lycophytes, to several monocots and eudicots. We
investigated the evolutionary relationship of GID1s using a comparative genomics
framework and found strong support for a previously proposed phylogenetic
classification of this family in land plants. We identified lineage-specific
expansions of particular subfamilies (i.e. GID1ac and GID1b) in different eudicot
lineages (e.g. GID1b in legumes). Further, we found both, shared and divergent
structural features between GID1ac and GID1b subgroups in eudicots that provide
mechanistic insights on their functions. Gene expression data from several
species show that at least one GID1 gene is expressed in every sampled tissue,
with a strong bias of GID1b expression towards underground tissues and dry legume
seeds (which typically have low GA levels). Taken together, our results indicate
that GID1ac retained canonical GA signaling roles, whereas GID1b specialized in
conditions of low GA concentrations. We propose that this functional
specialization occurred initially at the gene expression level and was later fine
tuned by mutations that conferred greater GA affinity to GID1b, including a Phe
residue in the GA-binding pocket. Finally, we discuss the importance of our
findings to understand the diversification of GA perception mechanisms in land
plants.
PMID- 29956115
TI - The Synergistic Impact of Sexual Stigma and Psychosocial Well-Being on HIV
Testing: A Mixed-Methods Study Among Nigerian Men who have Sex with Men.
AB - Although sexual stigma has been linked to decreased HIV testing among men who
have sex with men (MSM), mechanisms for this association are unclear. We
evaluated the role of psychosocial well-being in connecting sexual stigma and HIV
testing using an explanatory sequential mixed methods analysis of 25 qualitative
and 1480 quantitative interviews with MSM enrolled in a prospective cohort study
in Nigeria from March/2013-February/2016. Utilizing structural equation modeling,
we found a synergistic negative association between sexual stigma and suicidal
ideation on HIV testing. Qualitatively, prior stigma experiences often generated
psychological distress and perceptions of feeling unsafe, which decreased
willingness to seek services at general health facilities. MSM reported feeling
safe at the MSM-friendly study clinic but still described a need for psychosocial
support services. Addressing stigma and unmet mental health needs among Nigerian
MSM has the potential to improve HIV testing uptake.
PMID- 29956114
TI - The chromatin remodeler ZmCHB101 impacts expression of osmotic stress-responsive
genes in maize.
AB - KEY MESSAGE: The maize chromatin remodeler ZmCHB101 plays an essential role in
the osmotic stress response. ZmCHB101 controls nucleosome densities around
transcription start sites of essential stress-responsive genes. Drought and
osmotic stresses are recurring conditions that severely constrain crop
production. Evidence accumulated in the model plant Arabidopsis thaliana suggests
that core components of SWI/SNF chromatin remodeling complexes play essential
roles in abiotic stress responses. However, how maize SWI/SNF chromatin
remodeling complexes function in osmotic and drought stress responses remains
unknown. Here we show that ZmCHB101, a homolog of A. thaliana SWI3D in maize,
plays essential roles in osmotic and dehydration stress responses. ZmCHB101-RNA
interference (RNAi) transgenic plants displayed osmotic, salt and drought stress
sensitive phenotypes. Genome-wide RNA-sequencing analysis revealed that ZmCHB101
impacts the transcriptional expression landscape of osmotic stress-responsive
genes. Intriguingly, ZmCHB101 controls nucleosome densities around transcription
start sites of essential stress-responsive genes. Furthermore, we identified that
ZmCHB101 associates with RNA polymerase II (RNAPII) in vivo and is a prerequisite
for the proper occupancy of RNAPII on the proximal regions of transcription start
sites of stress-response genes. Taken together, our findings suggest that
ZmCHB101 affects gene expression by remodeling chromatin states and controls
RNAPII occupancies in maize under osmotic stress.
PMID- 29956117
TI - Extracorporeal Cardiopulmonary Resuscitation After Diphenhydramine Ingestion.
AB - INTRODUCTION: Diphenhydramine is a widely used first-generation histamine (H1)
antagonist that can be obtained without prescription in many countries. Massive
ingestions can result in severe toxicity and even death. We describe a case of
diphenhydramine overdose leading to cardiac arrest, cardiopulmonary resuscitation
(CPR), and extracorporeal membrane oxygenation (ECMO) cannulation for refractory
ventricular fibrillation, a process we refer to as extracorporeal cardiopulmonary
resuscitation (ECPR). CASE REPORT: Responding to a call for altered mental
status, emergency medical service (EMS) personnel found an unconscious and
seizing 17-year-old male. He had reportedly developed generalized tonic-clonic
seizures and dysrhythmias after ingesting approximately 800 25-mg diphenhydramine
tablets. He was transferred to our pediatric intensive care unit (PICU) after
stabilization at a local emergency center. After approximately 7 hours of
clinical stability and normalization of cardiac rhythm, electrolytes, and
acidosis, he developed renewed seizure activity and accelerated ventricular
rhythm leading to hemodynamic collapse and cardiac arrest. He was cannulated for
veno-arterial extracorporeal membrane oxygenation (VAECMO) with CPR in progress.
A pharmacobezoar located in his stomach was presumed to be the cause of his
biphasic clinical deterioration. After 5 days, the patient was successfully
weaned from ECMO support. Ten days later, his convalescence continued in the step
down unit and was discharged with good functional outcome. DISCUSSION:
Significant ingestion of anticholinergic substances is often fatal. This case
describes a favorable outcome after ECPR and aggressive supportive management
following a large intentional overdose of diphenhydramine.
PMID- 29956116
TI - The Role of Religious Service Attendance, Psychosocial and Behavioral
Determinants of Antiretroviral Therapy (ART) Adherence: Results from HPTN 063
Cohort Study.
AB - Early and sustained antiretroviral therapy (ART) adherence can suppress the HIV
virus in individuals and reduce onward transmission of HIV in the population.
Religiosity has been associated with better HIV clinical outcomes. Data are from
a longitudinal, observational study of 749 HIV-infected individuals from Brazil,
Zambia, and Thailand (HPTN 063). Ordered logistic regression assessed whether
religious service attendance was associated with ART adherence (self-reported and
plasma HIV-RNA) and moderated the association between alcohol problems and ART
adherence. In each country, > 80% of participants reported high self-reported ART
adherence (good/very good/excellent). Religious service attendance exceeded 85%
but was statistically unrelated to adherence. In combined-country models, (p =
0.03) as alcohol problems increased, the probability of high self-reported ART
adherence, as well as viral-load, became weaker at higher compared to low service
attendance frequency. Future studies should evaluate spirituality variables and
replicate the moderation analyses between religious attendance and alcohol
problems.
PMID- 29956118
TI - Near-Infrared Spatially Resolved Spectroscopy as an Indirect Technique to Assess
Brown Adipose Tissue in Young Women.
AB - PURPOSE: Near-infrared spectroscopy (NIRS) has recently been proposed as an
indirect technique to assess brown adipose tissue (BAT) in young men. NIRS arises
as a novel technique to avoid the limitations of the "gold-standard" 2-deoxy-2
[18F]fluoro-D-glucose ([18F]DG) positron emission tomography combined with X-ray
computed tomography (PET/CT). The aim of this study was to examine the
association between near-infrared spatially resolved spectroscopy (NIRSRS)
parameters and BAT volume and activity estimated by [18F]DG-PET/CT in 18 young
healthy women. PROCEDURES: NIRSRS parameters [tissue saturation index and
concentrations of total haemoglobin, oxy-haemoglobin, and deoxy-haemoglobin] were
continuously measured in the supraclavicular and forearm regions, in both warm
and cold (2 h of personalised cold exposure) conditions. Then, the NIRSRS data
were analysed as an average of 5 min in 4 different periods: (i) warm period as
the baseline record, (ii) cold period I, (iii) cold period II, and (iv) cold
period III. The data were then correlated with BAT volume and activity (SUVmean
and SUVpeak) estimated by [18F]DG-PET/CT. RESULTS: There was no association
between the NIRSRS parameters in the supraclavicular region in warm conditions
(no previous cold exposure) and BAT volume and activity (P > 0.05). Similarly,
the cold-induced changes of the NIRSRS parameters in the supraclavicular region
were not associated with BAT volume and activity (P > 0.05). CONCLUSIONS: NIRSRS
does not seem to be a valid technique to indirectly assess BAT in young healthy
women. Further research is needed to validate this technique against other
methods such as PET/CT using different radiotracers or magnetic resonance
imaging.
PMID- 29956119
TI - Quantitative Analysis of Heterogeneous [18F]FDG Static (SUV) vs. Patlak (Ki)
Whole-body PET Imaging Using Different Segmentation Methods: a Simulation Study.
AB - PURPOSE: Whole-body (WB) dynamic positron emission tomography (PET) enables
imaging of highly quantitative physiological uptake parameters beyond the
standardized uptake value (SUV). We present a novel dynamic WB anthropomorphic
PET simulation framework to assess the potential of 2-deoxy-2-[18F]fluoro-D
glucose ([18F]FDG) net uptake rate constant (Ki) imaging in characterizing tumor
heterogeneity. PROCEDURES: Validated heterogeneous [18F]FDG tumor kinetics were
modeled within the XCAT phantom (ground truth). Thereafter, static (SUV) and
dynamic PET data were simulated and reconstructed, followed by indirect WB Patlak
Ki imaging. Subsequently, we compared the methods of affinity propagation (AP)
and automatic segmentation with active contour (MASAC) to evaluate the impact of
tumor delineation. Finally, we extracted the metabolically active tumor volume
(MATV), Dice similarity coefficient (DSC), and the intratumoral heterogeneity
metrics of the area under the cumulative intensity histogram curve (CIHAUC),
homogeneity, entropy, dissimilarity, high-intensity emphasis (HIE), and zone
percentage (ZP), along with the target-to-background (TBR) and contrast-to-noise
ratios (CNR). RESULTS: Ki images presented higher TBR but lower CNR compared to
SUV. In contrast to MASAC, AP segmentation resulted in smaller bias for MATV and
DSC scores in Ki compared to SUV images. All metrics, except for ZP, were
significantly different in AP segmentation between SUV and Ki images, with
significant correlation observed for MATV, homogeneity, dissimilarity, and
entropy. With MASAC segmentation, CIHAUC, homogeneity, and dissimilarity were
significantly different between SUV and Ki images, with all metrics, except for
HIE and ZP, being significantly correlated. In ground truth images, increased
heterogeneity was observed with Ki compared to SUV, with a high correlation for
all metrics. CONCLUSIONS: A novel simulation framework was developed for the
assessment of the quantitative benefits of WB Patlak PET on realistic
heterogeneous tumor models. Quantitative analysis showed that WB Ki imaging may
provide enhanced TBR and facilitate lesion segmentation and quantification beyond
the SUV capabilities.
PMID- 29956120
TI - Smartphones, Sensors, and Machine Learning to Advance Real-Time Prediction and
Interventions for Suicide Prevention: a Review of Current Progress and Next
Steps.
AB - PURPOSE OF REVIEW: As rates of suicide continue to rise, there is urgent need for
innovative approaches to better understand, predict, and care for those at high
risk of suicide. Numerous mobile and sensor technology solutions have already
been proposed, are in development, or are already available today. This review
seeks to assess their clinical evidence and help the reader understand the
current state of the field. RECENT FINDINGS: Advances in smartphone sensing,
machine learning methods, and mobile apps directed towards reducing suicide offer
promising evidence; however, most of these innovative approaches are still
nascent. Further replication and validation of preliminary results is needed.
Whereas numerous promising mobile and sensor technology based solutions for real
time understanding, predicting, and caring for those at highest risk of suicide
are being studied today, their clinical utility remains largely unproven.
However, given both the rapid pace and vast scale of current research efforts, we
expect clinicians will soon see useful and impactful digital tools for this space
within the next 2 to 5 years.
PMID- 29956122
TI - Flavihumibacter profundi sp. nov., isolated from eutrophic freshwater sediment.
AB - A Gram-stain-positive, aerobic, non-motile, non-spore-forming, and rod-shaped
bacterium, designated strain CHu64-6-1T, was isolated from a 67-cm-long sediment
core collected from the Daechung Reservoir at a water depth of 17-m in Daejeon,
Republic of Korea. Comparative 16S rRNA gene sequence studies placed the new
isolate in the class Sphingobacteriia, and the isolate is notably most closely
related to Flavihumibacter sediminis CJ663T (98.1% similarity), Flavihumibacter
solisilvae 3-3T (97.8%), Flavihumibacter petaseus T41T (97.5%), Flavihumibacter
cheonanensis WS16T (97.4%), and Flavihumibacter stibioxidans YS-17T (97.2%). The
cells of strain CHu64-6-1T formed yellow colonies on R2A agar and contained MK-7
as the only menaquinone, phosphatidylethanolamine, an unidentified phospholipid,
and two unidentified aminolipids as the major polar lipids, and C15:0 iso, C17:0
iso 3-OH, C15:1 iso G, and C16:1omega5c as the major fatty acids (> 5%). The DNA
G + C content of the genome was determined to be 46.5 mol%. The DNA-DNA
hybridization values of strain CHu64-6-1T with F. sediminis CJ663T, F. solisilvae
3-3T, F. petaseus T41T, F. cheonanensis WS16T, and F. stibioxidans YS-17T were
12.4-33.2%. Based on the combined genotypic and phenotypic data, we propose that
strain CHu64-6-1T represents a novel species of the genus Flavihumibacter, for
which the name Flavihumibacter profundi sp. nov. is proposed. The type strain is
CHu64-6-1T (= KCTC 62290T = CCTCC AB 2018060T).
PMID- 29956123
TI - Hymenobacter jeollabukensis sp. nov., isolated from soil.
AB - A Gram-stain-negative, non-motile, rod-shaped, aerobic bacterial strain,
designated 1-3-3-8T, was isolated from soil and characterized taxonomically using
a polyphasic approach. Comparative 16S rRNA gene sequence analysis showed that
strain 1-3-3-8T belongs to the family Cytophagaceae of phylum Bacteroidetes and
is most closely related to Hymenobacter paludis KBP-30T (96.8% similarity),
Hymenobacter ocellatus Myx2105T (96.8%), Hymenobacter coalescens WW84T (95.6%),
and Hymenobacter deserti ZLB-3T (95.4%). The G + C content of the genomic DNA of
strain 1-3-3-8T was 63.6 mol%. The isolate contained C15:0 iso (28.4%), summed
feature 4 (C17:1 anteiso B/C17:1 iso I; 18.9%), and C15:0 anteiso (17.6%) as
major fatty acids, MK-7 as the predominant respiratory quinone, and sym
homospermidine as the predominant polyamine. The major polar lipids were
phosphatidylethanolamine and an unidentified lipid. The phenotypic and
chemotaxonomic data supported the affiliation of strain 1-3-3-8T with the genus
Hymenobacter. The DNA-DNA relatedness between strain 1-3-3-8T and H. paludis KCTC
32237T and H. ocellatus DSM 11117T were 24.5 and 27.4% respectively, clearly
showing that the isolate is not related to them at the species level. Overall,
the novel strain could be differentiated from its phylogenetic neighbors on the
basis of several phenotypic, genotypic, and chemotaxonomic features. Therefore,
strain 1-3-3-8T represents a novel species of the genus Hymenobacter, for which
the name Hymenobacter jeollabukensis sp. nov. has been proposed. The type strain
is 1-3-3-8T (= KCTC 52741T = JCM 32192T).
PMID- 29956121
TI - Identification of an enhancer region within the TP63/LEPREL1 locus containing
genetic variants associated with bladder cancer risk.
AB - PURPOSE: Genome-wide association studies (GWAS) have led to the identification of
a bladder cancer susceptibility variant (rs710521) in a non-coding intergenic
region between the TP63 and LEPREL1 genes on chromosome 3q28, suggesting a role
in the transcriptional regulation of these genes. In this study, we aimed to
functionally characterize the 3q28 bladder cancer risk locus. METHODS: Fine
mapping was performed by focusing on the region surrounding rs710521, and
variants were prioritized for further experiments using ENCODE regulatory data.
The enhancer activity of the identified region was evaluated using dual
luciferase assays. CRISPR/Cas9-mediated deletion of the enhancer region was
performed and the effect of this deletion on cell proliferation and gene
expression levels was evaluated using CellTiter-Glo and RT-qPCR, respectively.
RESULTS: Fine-mapping of the GWAS signal region led to the identification of
twenty SNPs that showed a stronger association with bladder cancer risk than
rs710521. Using publicly available data on regulatory elements and sequences, an
enhancer region containing the bladder cancer risk variants was identified.
Through reporter assays, we found that the presence of the enhancer region
significantly increased DeltaNTP63 promoter activity in bladder cancer-derived
cell lines. CRISPR/Cas9-mediated deletion of the enhancer region reduced the
viability of bladder cancer cells by decreasing the expression of DeltaNTP63 and
p63 target genes. CONCLUSIONS: Taken together, our data show that bladder cancer
risk-associated variants on chromosome 3q28 are located in an active enhancer
region. Further characterization of the allele-specific activity of the
identified enhancer and its target genes may lead to the identification of novel
signaling pathways involved in bladder carcinogenesis.
PMID- 29956124
TI - Antifungal activity of 3-acetylbenzamide produced by actinomycete WA23-4-4 from
the intestinal tract of Periplaneta americana.
AB - Actinomycetes are well-known for producing numerous bioactive secondary
metabolites. In this study, primary screening by antifungal activity assay found
one actinomycete strain WA23-4-4 isolated from the intestinal tract of
Periplaneta americana that exhibited broad spectrum antifungal activity. 16S rDNA
gene analysis of strain WA23-4-4 revealed close similarity to Streptomyces
nogalater (AB045886) with 86.6% sequence similarity. Strain WA23-4-4 was
considered as a novel Streptomyces and the 16s rDNA sequence has been submitted
to GenBank (accession no. KX291006). The maximum antifungal activity of WA23-4-4
was achieved when culture conditions were optimized to pH 8.0, with 12% inoculum
concentration and 210 ml ISP2 medium, which remained stable between the 5th and
the 9th day. 3-Acetyl benzoyl amide was isolated by ethyl acetate extraction of
WA23-4-4 fermentation broth, and its molecular formula was determined as C9H9NO2
based on MS, IR, 1H, and 13C NMR analyses. The compound showed significant
antifungal activity against Candida albicans ATCC 10231 (MIC: 31.25 MUg/ml) and
Aspergillus niger ATCC 16404 (MIC: 31.25 MUg/ml). However, the compound had
higher MIC values against Trichophyton rubrum ATCC 60836 (MIC: 500 MUg/ml) and
Aspergillus fumigatus ATCC 96918 (MIC: 1,000 MUg/ml). SEM analysis showed damage
to the cell membrane of Candida albicans ATCC 10231 and to the mycelium of
Aspergillus niger ATCC 16404 after being treatment with 3-acetyl benzoyl amide.
In conclusion, this is the first time that 3-acetyl benzoyl amide has been
identified from an actinomycete and this compound exhibited antifungal activity
against Candida albicans ATCC 10231 and Aspergillus niger ATCC 16404.
PMID- 29956125
TI - Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in
CNS function with and without injury.
AB - The mammalian central nervous system (CNS) is considered an immune privileged
system as it is separated from the periphery by the blood brain barrier (BBB).
Yet, immune functions have been postulated to heavily influence the functional
state of the CNS, especially after injury or during neurodegeneration. There is
controversy regarding whether adaptive immune responses are beneficial or
detrimental to CNS injury repair. In this study, we utilized immunocompromised
SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor
function, electrophysiology, histochemistry, and performed unbiased RNA
sequencing. SCID mice displayed improved CNS functional recovery compared to WT
mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal
cord transcriptomes revealed that SCID mice had reduced expression of immune
function-related genes and heightened expression of neural transmission-related
genes after SCI, which was confirmed by immunohistochemical analysis and was
consistent with better functional recovery. Transcriptomic analyses also
indicated heightened expression of neurotransmission-related genes before injury
in SCID mice, suggesting that a steady state of immune-deficiency potentially led
to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated
worse performance in Morris water maze test. Taken together, not only reduced
inflammation after injury but also dampened steady-state immune function without
injury heightened the neurotransmission program, resulting in better or worse
behavioral outcomes respectively. This study revealed the intricate relationship
between immune and nervous systems, raising the possibility for therapeutic
manipulation of neural function via immune modulation.
PMID- 29956126
TI - Health correlates, addictive behaviors, and peer victimization among adolescents
in China.
AB - BACKGROUND: Peer victimization has been recognized as a common social problem
affecting children and adolescents in all parts of the world. This study aims to
examine the prevalence of different types of peer victimization and to evaluate
the associations between peer victimization and health correlates. METHODS: Using
a large population sample of 18,341 adolescents aged 15-17 years from 6 cities in
China, this study estimated the prevalence of different types of peer
victimization, addictive behaviors, and health-related variables with self
administrated questionnaires. A three-phase logistical regression analysis was
conducted to investigate the associations between peer victimization and
addictive behaviors as well as health-related factors among adolescents. RESULTS:
A total of 42.9% of the surveyed Chinese adolescents have been bullied by peers,
with boys reporting higher rate on overt victimization (36.9%) and girls on
relational forms (33.9%). School environment (34.7%) was the most frequent scene
of peer violence, followed by neighborhood, family, and internet. Addictive
behaviors except substance abuse were found related to higher possibility of peer
victimization (aOR 1.21-1.73, P < 0.001). Peer victimization was significantly
associated with more depressive symptoms, post-traumatic stress disorder
symptoms, and suicide ideation and deliberate self-harm (aOR 1.05-2.27, P <
0.001), and poorer self-esteem and health-related quality of life (aOR 0.95-0.97,
P < 0.001). CONCLUSION: Possible explanations of the associations found in this
study are discussed and implications for future services are raised.
PMID- 29956127
TI - Barriers Faced by the Health Workers to Deliver Maternal Care Services and Their
Perceptions of the Factors Preventing Their Clients from Receiving the Services:
A Qualitative Study in South Sudan.
AB - Objective The study objective was to explore challenges and barriers confronted
by maternal and child healthcare providers to deliver adequate quality health
services to women during antenatal care visits, facility delivery and post
delivery care. Methods We conducted 18 in-depth-interviews with maternal and
child health professionals including midwives/nurses, trained traditional birth
attendants (TBAs), gynecologists, and pediatricians in three public health
facilities in Juba, South Sudan. We purposively selected these health
professionals to obtain insights into service delivery processes. We analyzed the
data using thematic analysis. Results Limited support from the heath system, such
as poor management and coordination of staff, lack of medical equipment and
supplies and lack of utilities such as electricity and water supply were major
barriers to provision of health services. In addition, lack of supervision and
training opportunity, low salary and absence of other forms of non-financial
incentives were major elements of health workers' de-motivation and low
performance. Furthermore, security instability as a result of political and armed
conflicts further impact services delivery. Conclusions for Practice This study
highlighted the urgent need for improving maternal and child healthcare services
such as availability of medical supplies, equipment and utilities. The necessity
of equal training opportunities for maternal and child healthcare workers at
different levels were also stressed. Assurance of safety of health workers,
especially at night, is essential for providing of delivery services.
PMID- 29956128
TI - Inequality and Innovation: Barriers and Facilitators to 17P Administration to
Prevent Preterm Birth among Medicaid Participants.
AB - Objectives Strategies to prevent preterm birth are limited. 17 Alpha
Hydroxyprogesterone Caproate (17P) injections have been shown to be effective,
but the intervention is under-used. This mixed methods study investigates
barriers and facilitators to 17P administration among Medicaid and CHIP
participants enrolled in Strong Start for Mothers and Newborns, a federal preterm
birth prevention program. Methods Twenty-seven awardees with more than 200 sites
in 30 states, the District of Columbia, and Puerto Rico enrolled approximately
46,000 women in Strong Start from 2013 to 2016. Participant data, including data
on preterm birth and 17P, was collected for each woman. Intensive interviews (n =
211) conducted with Strong Start program staff and providers (n = 314) included
questions about 17P provision. Results Of women whose data included a valid
response regarding 17P initiation, 3919 had a prior preterm birth and current
singleton pregnancy; 14.95% received 17P. Barriers to 17P administration include
late entry to prenatal care, administrative burden of preauthorization, cost
risks to providers, limits in scope of practice for non-physician providers, and
social barriers among participants. Facilitators for provision include
streamlined work flows and the option of home administration. Conclusions for
Practice A universal insurance authorization process could mitigate many barriers
to 17P use. Providers need continuing education regarding the effectiveness of
17P, and expanding scope of practice for non-physician prenatal care providers
would increase access. Targeted program interventions can help to overcome social
barriers Medicaid participants face in accessing care. Streamlined work processes
and the option of home health services are two effective program-based
facilitators for providing 17P to a Medicaid population.
PMID- 29956129
TI - Socioeconomic Position and Reproduction: Findings from the Australian
Longitudinal Study on Women's Health.
AB - OBJECTIVE: To investigate the association of socioeconomic position (SEP) with
reproductive outcomes among Australian women. METHODS: Data from the Australian
Longitudinal Study on Women's Health's (population-based cohort study) 1973-1978
cohort were used (N = 6899, aged 37-42 years in 2015). The association of SEP
(childhood and own, multiple indicators) with age at first birth, birth-to
pregnancy (BTP) intervals and total number of children was analysed using
multinomial logistic regression. RESULTS: 14% of women had their first birth aged
< 24 years. 29% of multiparous women had a BTP interval within the WHO
recommendation (18-27 months). Women with a low SEP had increased odds of a first
birth < 24 years: low (OR 7.0: 95% C.I. 5.3, 9.3) or intermediate education (OR
3.8: 2.8, 5.1); living in rural (OR 1.8: 1.5, 2.2) or remote (OR 2.1: 1.7, 2.7)
areas; who found it sometimes (OR 1.8: 1.5, 2.2) or always difficult (OR 2.0:
1.6, 2.7) to manage on their income; and did not know their parent's education
(OR 4.5: 3.2, 6.4). Low SEP was associated with having a much longer than
recommended BTP interval. CONCLUSION: As the first Australian study describing
social differences in reproductive characteristics, these findings provide a base
for reducing social inequalities in reproduction. Assisting adequate BTP spacing
is important, particularly for women with existing elevated risks due to social
disadvantage; including having a first birth < 24 years of age and a longer than
recommended BTP interval. This includes reviewing services/access to postnatal
support, free family planning/contraception clinics, and improved family
policies.
PMID- 29956130
TI - QModeling: a Multiplatform, Easy-to-Use and Open-Source Toolbox for PET Kinetic
Analysis.
AB - Kinetic modeling is at the basis of most quantification methods for dynamic PET
data. Specific software is required for it, and a free and easy-to-use kinetic
analysis toolbox can facilitate routine work for clinical research. The relevance
of kinetic modeling for neuroimaging encourages its incorporation into image
processing pipelines like those of SPM, also providing preprocessing flexibility
to match the needs of users. The aim of this work was to develop such a toolbox:
QModeling. It implements four widely-used reference-region models: Simplified
Reference Tissue Model (SRTM), Simplified Reference Tissue Model 2 (SRTM2),
Patlak Reference and Logan Reference. A preliminary validation was also
performed: The obtained parameters were compared with the gold standard provided
by PMOD, the most commonly-used software in this field. Execution speed was also
compared, for time-activity curve (TAC) estimation, model fitting and image
generation. QModeling has a simple interface, which guides the user through the
analysis: Loading data, obtaining TACs, preprocessing the model for pre
evaluation, generating parametric images and visualizing them. Relative
differences between QModeling and PMOD in the parameter values are almost always
below 10-8. The SRTM2 algorithm yields relative differences from 10-3 to 10-5
when [Formula: see text] is not fixed, since different, validated methods are
used to fit this parameter. The new toolbox works efficiently, with execution
times of the same order as those of PMOD. Therefore, QModeling allows applying
reference-region models with reliable results in efficient computation times. It
is free, flexible, multiplatform, easy-to-use and open-source, and it can be
easily expanded with new models.
PMID- 29956131
TI - Using Deep Learning Algorithms to Automatically Identify the Brain MRI Contrast:
Implications for Managing Large Databases.
AB - Neuroimaging science has seen a recent explosion in dataset size driving the need
to develop database management with efficient processing pipelines. Multi-center
neuroimaging databases consistently receive magnetic resonance imaging (MRI) data
with unlabeled or incorrectly labeled contrast. There is a need to automatically
identify the contrast of MRI scans to save database-managing facilities valuable
resources spent by trained technicians required for visual inspection. We
developed a deep learning (DL) algorithm with convolution neural network
architecture to automatically infer the contrast of MRI scans based on the image
intensity of multiple slices. For comparison, we developed a random forest (RF)
algorithm to automatically infer the contrast of MRI scans based on acquisition
parameters. The DL algorithm was able to automatically identify the MRI contrast
of an unseen dataset with <0.2% error rate. The RF algorithm was able to identify
the MRI contrast of the same dataset with 1.74% error rate. Our analysis showed
that reduced dataset sizes caused the DL algorithm to lose generalizability.
Finally, we developed a confidence measure, which made it possible to detect,
with 100% specificity, all MRI volumes that were misclassified by the DL
algorithm. This confidence measure can be used to alert the user on the need to
inspect the small fraction of MRI volumes that are prone to misclassification.
Our study introduces a practical solution for automatically identifying the MRI
contrast. Furthermore, it demonstrates the powerful combination of convolution
neural networks and DL for analyzing large MRI datasets.
PMID- 29956132
TI - Serum Arginase II level can be a novel indicator for erectile dysfunction in
patients with vasculogenic erectile dysfunction: a comparative study.
AB - PURPOSE: The purpose of the study was to compare serum level of Arginase II in
patients with vasculogenic erectile dysfunction (ED) versus healthy controls and
to assess if its level is affected by severity of ED. METHODS: This is a
prospective study that compared Arginase II in 40 patients with ED versus 40
healthy controls. Patients were excluded if they had any pelvic trauma or pelvic
surgery, hormonal disorders, Peyronie's disease, smoking, drug addiction or
systemic illnesses. ED was evaluated by the validated Arabic version of the
abbreviated five-item form of the international index of erectile function (IIEF
5). Serum arginase II level was assayed using ELIZA. Mann-Whitney, Kruskal-Wallis
and Chi-square tests and Spearman correlation were used as appropriate and
confirmed by logistic regression model. RESULTS: 22 (55%) patients had DM. 15
(37.5%), 7 (17%), 6 (15%) and 12 (30%) patients suffered from severe, moderate,
mild to moderate and mild ED, respectively. The level of serum Arginase II was
significantly higher in patients than controls (p < 0.001) and confirmed by
multivariate logistic regression analysis. It also correlated significantly with
age (r2 = 0.22; p < 0.001) and IIEF-5 score (r2 = 0.8; p < 0.001). Serum Arginase
II increased significantly with more severe ED (p < 0.001). Arginase II was also
significantly higher in diabetic patients (p < 0.001). CONCLUSION: Serum level of
Arginase II is significantly higher in patients with vasculogenic ED compared to
healthy controls. It correlates significantly with age and IIEF-5 and was
significantly affected by the severity of ED.
PMID- 29956133
TI - Quantifying the medication burden of kidney transplant recipients in the first
year post-transplantation.
AB - Background Kidney transplantation is an effective treatment, but it is not a
cure. Since the risk of graft rejection and the presence of comorbid conditions
remain for a lifetime, medications are necessary. Objective To examine the
prescription medication burden of adult kidney transplant recipients from 3- to
12-months post-transplantation. Setting All five adult kidney transplant units in
Victoria, Australia. Method As part of a larger intervention study, we conducted
a retrospective review of prescription refill records and medical records
containing the history of medication changes of 64 participants who completed the
study. The complexity of the medication management was studied, and we looked at
the burden of maintaining the medications supply. Outcome measures Pill burden,
administration frequency, dose changes frequency, immunosuppressive medication
changes, the estimated out-of-pocket costs of medications and frequency of
pharmacy visits. Results At 3 months, the average daily pill burden was 22 (SD =
9) whilst at 12 months, it was 23 (SD = 10). Some participants required long-term
prophylaxis of fungal infections up to 4 times a day whilst those with diabetes
had to manage up to 4 insulin doses a day. The average out-of-pocket cost per
person and the frequency of pharmacy visits at 6, 9 and 12 months post
transplantation remained relatively unchanged. Conclusion The medication regimen
prescribed for kidney transplant recipients is complex and for most patients, it
did not simplify over time post transplantation. Strategies are needed to support
patients in managing the complexity of their medication regimen following kidney
transplantation.
PMID- 29956134
TI - Outcomes of warfarin therapy managed by pharmacists via hospital anticoagulation
clinic versus online anticoagulation clinic.
AB - Background In response to the recognized difficulty in the management of patients
on anticoagulation therapy, anticoagulation management services were developed in
both hospital anticoagulation clinics (HACs) and an online anticoagulation clinic
(OAC) by a pharmacist. Objective To compare monitoring outcomes and complications
of warfarin therapy managed by pharmacists via hospital or on-line. Setting The
anticoagulation clinic of Fujian Medical University Union Hospital, China. Method
A retrospective, observational cohort study was used to compare patients managed
via hospital to those managed o-line between December 2015 and 2016. The primary
outcome was the percentage of time in the therapeutic range (TTR). The secondary
outcomes were the incidence rates of hemorrhagic events, thrombotic events and
extreme international normalized ratio (INR) values. Results A total of 152
patients were evaluated; 70 patients managed in a HAC were compared to 82
patients managed via an OAC. There were no significant differences in the TTR
(78.9 vs. 74.0%, P = 0.393) and adverse events [major bleeding events (0 vs.
1.2%, P = 1.000), minor bleeding events (10.0 vs. 9.8%, P = 0.960),
thromboembolic events (0 vs. 0%, P = 1.000), warfarin-related emergency visits
(2.9 vs. 3.7%, P = 1.000)], warfarin-related hospital admissions (0 vs. 1.2%, P =
1.000), and the incidence of subtherapeutic (3.0 vs. 3.8%, P = 0.148), and
extreme total (8.4 vs. 5.8%, P = 0.135), between the groups managed via HAC and
OAC. Patients managed in the HAC were more stable on warfarin, with a higher
percentage of INR values within the target therapeutic range (80.2 vs. 71.9%, P =
0.005) and a lower incidence of supratherapeutic INR values (8.4 vs. 18.5%, P =
0.001) compared to patients managed via OAC. Conclusion The management of oral
anticoagulation therapy on-line yielded similar clinical outcomes compared to
that achieved by management via the hospital, although the incidence of supra
therapeutic INR values was increased.
PMID- 29956135
TI - Esophageal perforation: a research review of the anti-infective treatment.
AB - Background Esophageal perforation is a complex disease state and often difficult
to diagnose due to the variability in patient presentation. The chosen anti
infective treatment and duration of anti-infective therapy that patients with
esophageal perforation receive has been inconsistent. Choice of anti-infective
treatment and duration of therapy may also be highly variable from institution to
institution, and can even vary by provider. To our knowledge, there has not been
a publication reviewing esophageal perforation with a specific focus on
pharmacologic management. Aim of the review The aim of this study is to summarize
pertinent research articles focused on the anti-infective treatment of adult
patients diagnosed with esophageal perforation. Method Pubmed electronic database
was utilized to search for articles meeting pre-defined criteria. Articles were
included in this review if they discussed at least 1 of the following 3 criteria:
choice of anti-infective treatment regimen, duration of anti-infective therapy,
or identification of organisms growing from cultures associated with the
esophageal perforation. Results Seventy-seven articles included information
related to our research question. No randomized-controlled trials were identified
and only 7 identified articles reported all 3 criteria of interest. Conclusion
Review of the literature from 1979 to 2017 reveals the need for high quality
evidence related to anti-infective treatment in patients diagnosed with
esophageal perforation.
PMID- 29956136
TI - Production of Gas-Phase Uranium Fluoroanions Via Solubilization of Uranium Oxides
in the [1-Ethyl-3-Methylimidazolium]+[F(HF)2.3]- Ionic Liquid.
AB - A new methodology for gas-phase uranium ion formation is described in which UO2
is dissolved in neat N-ethyl,N'-methylimidazolium fluorohydrogenate ionic liquid
[EMIm+][F(HF)2.3-], yielding a blue-green solution. The solution was diluted with
acetonitrile and then analyzed by electrospray ionization mass spectrometry. UF6-
(a U(V) species) was observed at m/z = 352, and other than cluster ions derived
from the ionic liquid, nothing else was observed. When the sample was analyzed
using infusion desorption chemical ionization, UF6- was the base peak, and it was
accompanied by a less intense UF5- that most likely was formed by elimination of
a fluorine radical from UF6-. Formation of UF6- required dissolution of UO2
followed by or concurrent with oxidation of uranium from the + 4 to the + 5 state
and finally formation of the fluorouranate. Dissolution of UO3 produced a bright
yellow solution indicative of a U(VI) species; however, electrospray ionization
did not produce abundant U-containing ions. The abundant UF6- provides a vehicle
for accurate measurement of uranium isotopic abundances free from interference
from minor isotopes of other elements and a convenient ion synthesis route that
is needed gas-phase structure and reactivity studies like infrared multiphoton
dissociation and ion-molecule dissociation and condensation reactions. The
reactive fluorohydrogenate ionic liquid may also enable conversion of uranium in
oxidic matrices into uranium fluorides that slowly oxidize to uranyl fluoride
under ambient conditions, liberating the metal for facile measurement of isotope
ratios without extensive chemical separations. Graphical abstract ?.
PMID- 29956137
TI - A new opportunity: metabolism and neuropsychiatric disorders.
PMID- 29956138
TI - Correction to: Effects of Dendrimer-Like Biopolymers on Physical Stability of
Amorphous Solid Dispersions and Drug Permeability Across Caco-2 Cell Monolayers.
AB - During the production process, an editorial error occurred where the label
numbering for the first two tables were inadvertently switched. The original
article has been corrected.
PMID- 29956139
TI - A Fungal Protease Model to Interrogate Allergic Lung Immunity.
AB - Allergic airway diseases (asthma and chronic rhinosinusitis) are among the most
common of all human diseases in heavily industrialized societies. Animal models
of asthma have provided remarkable insight into allergic disease pathogenesis and
will continue to drive the discovery of new therapeutic insights. We provide in
this chapter a detailed protocol for inducing allergic immunity in the lungs of
mice using a purified fungal protease and include related protocols for assessing
immune endpoints.
PMID- 29956140
TI - Use of the Litomosoides sigmodontis Infection Model of Filariasis to Study Type 2
Immunity.
AB - Helminth parasites infect over 2 billion people worldwide resulting in huge
global health and economic burden. Helminths typically stimulate Type 2 immune
responses and excel at manipulating or suppressing host-immune responses
resulting in chronic infections that can last for years to decades. Alongside the
importance for the development of helminth treatments and vaccines, studying
helminth immunity has unraveled many fundamental aspects of Type 2 immunity and
immune regulation with implications for the treatment of autoimmunity and Type 2
mediated diseases, such as allergies. Here we describe the maintenance and use of
Litomosoides sigmodontis, a murine model for studying host-parasite interactions,
Type 2 immunity, and vaccines to tissue-dwelling filarial nematodes, which in
humans cause lymphatic filariasis (e.g., Brugia malayi) and onchocerciasis
(Onchocerca volvulus).
PMID- 29956141
TI - Production of Hymenolepis diminuta in the Laboratory: An Old Research Tool with
New Clinical Applications.
AB - Hymenolepis diminuta, the rat tapeworm, was first described in 1819 by Rudolphi
and was studied extensively in several laboratories during the mid to latter part
of the twentieth century. More recently, the primary use of the organism had been
for educational purposes. The organisms require an intermediate insect host to
complete their life cycle, making them non-transmissible to other rats or to
humans under typical laboratory or educational environments. The organisms
effectively colonize rats, but not humans or mice, and are easily maintained in
laboratory. They are, with exceedingly rare exceptions, benign (e.g.,
nonparasitic) in humans, mice, and laboratory rats. Although the benign character
of the helminth makes it ideal for educational purposes, the fact that no
pathology is associated with colonization has led to decreased interest in the H.
diminuta as a model for modern research where efforts are largely motivated by
interests in medicine and health. However, more recently work with the "biota
alteration" model of inflammatory disease has established that reintroduction of
helminths into Western society, a practice often referred to as "helminthic
therapy," is potentially a way of lowering inflammation without compromising
immune function. For this effort, the lack of pathology and benign nature of the
organism makes H. diminuta an ideal subject for study. In this chapter, we
describe production of H. diminuta using laboratory rats and introduction of the
organisms into laboratory mice as a model for their effects in humans.
PMID- 29956142
TI - A Mouse Model of Peanut Allergy Induced by Sensitization Through the
Gastrointestinal Tract.
AB - Animal models of disease enable the study of the pathology, biomarkers, and
treatments for the disease being studied. These models become particularly useful
in the study of diseases, such as peanut allergy, that currently have no FDA
approved therapy options. Here, we describe a mouse model of peanut allergy using
a peanut extract and cholera toxin that can be applied to both BALB/c and C3H/HeJ
mouse strains. Sensitization is induced through the gastrointestinal tract
resulting in elevated levels of peanut-specific IgE and anaphylaxis upon
challenge with peanut proteins. This model has been used to study the cells and
molecules involved in the development of peanut allergy and to evaluate novel
immunotherapy approaches and the underlying mechanisms of immunotherapy.
Potential utilities of this model are numerous and may include studies on
microbial influences on peanut allergy and discovery of biomarkers of
anaphylaxis.
PMID- 29956143
TI - Induction and Characterization of the Allergic Eye Disease Mouse Model.
AB - Ocular IgE-associated allergy ranges from mild disease (seasonal and perennial
allergic conjunctivitis) to more chronic/severe and vision-threatening forms
(atopic and vernal keratoconjunctivitis). Whereas mild forms of disease have been
studied extensively, less is known about the more chronic forms. Our lab has
helped to address this knowledge gap by developing and characterizing an allergen
induced, chronic/severe, IgE-associated model of ocular allergy referred to as
the severe allergic eye disease (AED) model. It is distinct from previously
described models that mimic the more mild forms, referred to in the literature as
the allergic conjunctivitis (AC) model. The purpose of this method article is to
detail the protocol to induce and characterize the AED model and directly compare
these mice to the mild AC model. Troubleshooting and implications are also
discussed.
PMID- 29956144
TI - Isolation and Purification of Epithelial and Endothelial Cells from Mouse Lung.
AB - It is well established that responses to inhaled environmental agents are
controlled by the coordinated actions by multiple immune cell types, including
macrophages, dendritic cells, and lymphocytes. Recent evidence indicates that
some structural cells can also contribute to the initiation and propagation of
immune responses. For example, airway epithelial cells can promote eosinophilic
inflammation in response to allergen inhalation. Much remains to be learned,
however, regarding how each of these cell types interact with the others, and how
these interactions shape immune responses to inhaled agents. Such studies have
been hampered by the lack of reliable methods to isolate multiple and distinct
populations of cells from the same tissue sample. Consequently, investigators
have had to choose between using different protocols to isolate different
populations of cells from different animals and accept that for some populations,
cell yields can be very low. To overcome these difficulties, we have developed a
convenient and practical method to isolate and purify subpopulations of
epithelial and endothelial cells from mouse lung. Here, we describe these methods
in detail.
PMID- 29956145
TI - In Vitro and In Vivo IgE-/Antigen-Mediated Mast Cell Activation.
AB - Mast cells (MCs) are major effectors of IgE-mediated allergic reactions because
of their unique peripheral location and their powerful capacity to release
prestored and de novo-synthesized inflammatory mediators into the circulation
upon activation. In view of the growing incidence of allergy worldwide, there is
much interest in developing novel strategies to block or temper IgE-mediated MC
activation and its pathological consequences. For these studies, standard assays
to measure IgE-mediated MC degranulation and mediator release are required. Here,
we present detailed procedures to assess in vitro and in vivo MC release of
prestored as well as recently synthesized mediators following IgE-/antigen
mediated activation.
PMID- 29956146
TI - The Use of Human and Mouse Mast Cell and Basophil Cultures to Assess Type 2
Inflammation.
AB - Mast cells and basophils are important innate immune cells involved in resistance
to parasitic infection and are critical orchestrators of allergic disease. The
relative ease with which they are cultured from mouse or human tissues allows one
to work with primary cells that maintain a differentiated and functional
phenotype. In this chapter, we describe the methods by which mouse mast cells and
basophils can be cultured from bone marrow. We also provide methods for isolating
and expanding mouse peritoneal mast cells and human skin mast cells.
PMID- 29956148
TI - Determination of the Fate and Function of Innate Lymphoid Cells Following
Adoptive Transfer of Innate Lymphoid Cell Precursors.
AB - Innate lymphoid cells are a heterogeneous family of tissue-resident and
circulating lymphocytes that play an important role in host immunity. Recent
studies have profiled the developmental pathways of mature ILCs and have
identified ILC progenitors in the bone marrow through the use of transcription
factor reporter mice. Here we describe methodology to identify and isolate bone
marrow CHILP and ILC2 progenitor (ILC2P) cells based on cell surface marker
expression for adoptive transfer into lymphopenic mice to track the fate of
developing ILCs.
PMID- 29956147
TI - Isolation and Identification of Group 2 Innate Lymphoid Cells in Settings of Type
2 Inflammation.
AB - The recent discovery of innate lymphoid cells (ILCs), a major source of canonical
T cell cytokines, has prompted significant interest into understanding the role
of these novel cells in immune responses. Unlike T cells, ILCs lack antigen
receptors, instead receiving activation from locally derived tissue signals.
Group 2 ILCs (ILC2s), which express the genes encoding GATA-3, interleukin (IL)
4, IL-5, IL-9, and IL-13, are distributed throughout nonlymphoid tissues.
Although ILC2s lack antigen receptors, there are considerable similarities that
they share with their Th2 cell counterparts, including receptors, secreted
signals, and key transcription factors. Here we describe a method of isolating
ILC2s for analysis from peripheral tissues of the mouse. The approach consists of
digesting and mechanically dissociating harvested organs followed by staining
with fluorescently labeled antibodies for flow cytometry or cell sorting. We
suggest panels of antibodies for each tissue that can be used as positive and
negative markers to selectively separate ILC2s from other cells, and we
demonstrate marker specificity with example cells from a "cytokine reporter"
mouse strain.
PMID- 29956149
TI - Characterization of Thymic Development of Natural Killer T Cell Subsets by
Multiparameter Flow Cytometry.
AB - Natural killer T (NKT) cells are a subset of alphabeta T cells that recognize
lipid antigens presented by the nonclassical MHC molecule CD1d. Although
numerically small, these cells have been shown to play an important role in the
regulation of multiple immune responses, including microbial infection,
autoimmunity, and cancer. Even in the steady state, cytokine production by NKT
cells influences the basal status and function of other immune cells, including
dendritic cells and CD8 T cells. To fully understand their biology and harness
them in the clinic, it is imperative to dissect the molecular mechanisms involved
in the acquisition of their functionality. Unlike conventional alphabeta T cells,
NKT cells acquire their effector function during development in the thymus. At
this time, precursors commit to one of three functionally different effector
lineages: NKT1, NKT2, and NKT17. These subsets are characterized by the secretion
of different cytokines upon antigenic stimulation and by the expression of the
master transcription factors Tbet, promyelocytic leukemia zinc finger (PLZF), and
retinoic orphan receptor gamma t (RORgammat). Here we describe a multicolor flow
cytometry protocol to identify NKT cell subsets and interrogate the progression
of NKT precursors through their development in the thymus.
PMID- 29956150
TI - Characterization of Mouse gammadelta T Cell Subsets in the Setting of Type-2
Immunity.
AB - Accumulating evidence indicates that gammadelta T cells are a critical component
of type-2 immunity. However, the role of these cells in type-2 immune responses
seems to be divergent. gammadelta T cells are heterogeneous lymphocytes that can
be further divided into TCR-Vgamma/delta definable subsets. Different subsets
have distinct and sometimes opposite function during immune responses. In this
chapter, we describe the detailed protocol for characterization of gammadelta T
cell subsets in a mouse model of ovalbumin (OVA)/alum-induced type-2 immunity.
Our protocol includes identifying gammadelta T cell subsets by flow cytometry,
functionally inactivating individual subsets in vivo, purifying gammadelta T cell
subsets, and using adoptive cell transfer to explore the role of individual
subsets in OVA/alum-induced IgE responses.
PMID- 29956151
TI - The Identification of Allergen-Derived T Cell Epitopes.
AB - Type I allergy is a disease primarily mediated by immunoglobulin E (IgE) and T
helper type 2 (Th2) cells. The role of Th2 and other T cell subsets in the
pathology of allergic disease as well as induction of tolerance has become an
area of intense research over the last decades. Studying allergen-specific T
cells to gain a better understanding of their contribution to allergic pathology
and how they are modulated by allergen-specific immunotherapy requires knowledge
of the allergens targeted by these cells. Identification of T cell epitopes in
allergy can be achieved by a variety of methods. In this chapter, we will focus
on a technique named FluoroSpot, which relies on the detection of cytokines
secreted by T cells in response to stimulation with an antigen (allergen), such
as timothy grass (TG) extract or an allergen-derived peptide, for which the cell
is specific. We will describe how to overcome the challenge of detecting rare, TG
specific, T cells that occur at low frequency in the blood by using an in vitro
expansion culture and subsequent mapping of the precise T cell epitope using
FluoroSpot.
PMID- 29956152
TI - Generation of Allergen-Specific Tetramers for a Murine Model of Airway
Inflammation.
AB - The identification and analysis of allergen-specific CD4+ T cells is critical for
understanding how these cells contribute to atopic disease and how to subvert
their behavior through immune therapy. The advent of fluorescently labeled
soluble tetramers of peptide:MHCII complexes (pMHCII tetramers) has provided
investigators with an invaluable means to achieve this goal. Although pMHCII
tetramers were first developed over two decades ago, their widespread use has
been limited by the technical difficulty of generating these reagents. However,
the adoption of various technical innovations from several labs over time has
contributed greatly to the increased success in tetramer generation today. Here,
we describe a comprehensive protocol for generating pMHCII tetramers using as an
example a Derp1:I-Ab tetramer used to study allergen-specific CD4+ T cell
responses in murine models of airway inflammation and allergic disease.
PMID- 29956153
TI - The Generation and Use of Allergen-Specific TCR Transgenic Animals.
AB - The generation of allergen-specific TCR transgenic animals allows for the
characterization of allergen-specific T-cell responses in vivo and in vitro and
is a powerful tool to study adaptive immunity to allergens. Here we describe an
approach starting from the isolation of antigen-specific T-cell hybridomas and
using PCR, flow cytometric, and co-culture methods to obtain antigen-specific MHC
class II-restricted CD4+ TCR transgenic mice on the Rag2-/- background.
PMID- 29956154
TI - Using Cytokine Reporter Mice to Visualize Type-2 Immunity In Vivo.
AB - Type-2 cytokine production plays a critical role in the context of type 2
immunity and allergic inflammation. Interleukin-4 (IL-4) and IL-13 are key
modulators of the cell-mediated and humoral immune hallmarks most commonly
associated with type-2 immune responses. However, production of these cytokines
by lymphocytes and their tissue localization has been difficult to detect in
vivo. As such, the field has relied heavily on ex vivo restimulation and in vitro
differentiation assays to understand type-2 cytokine biology. Although these
studies have greatly informed our understanding of type-2 cytokine regulation, it
is becoming increasingly clear that the data does not always provide a true
accounting of the complexity of type-2 immune cell biology in vivo. Described
below is a protocol used to detect IL-4-competent and protein-producing cells in
the lung and lymph nodes of mice after infection with a helminth. Importantly,
this protocol has also been used to successfully identify reporter expression and
cell function in vivo using various other cytokine-reporter systems.
PMID- 29956155
TI - Live Imaging of IL-4-Expressing T Follicular Helper Cells in Explanted Lymph
Nodes.
AB - The generation of class-switched, high-affinity, antibody-producing B cells plays
a critical role in the establishment of type 2 immunity to intestinal helminths
as well as in the pathogenesis of allergy and asthma. The generation of these
high-affinity, antibody-producing B cells occurs in germinal centers (GC) and
relies on interactions with follicular dendritic cells (FDCs) and T follicular
helper (Tfh) cells. One critical mediator produced by Tfh cells in GCs is
interleukin-4 (IL-4). Tfh-derived IL-4 drives class switching to type 2 antibody
isotypes IgE and IgG1 and is required for high-affinity IgG1 production. In vivo
detection of IL-4-expressing Tfh cells is required to better understand the role
of these cells during the GC response. Detection of IL-4-expressing cells has
been greatly improved by the generation of the IL-44get reporter mice, which read
out IL-4 expression as green fluorescent protein (GFP). Much has been learned
from these mice with regard to type 2 immunity using flow cytometry and
immunohistochemistry. However, these methods do not allow the study of cellular
behavior and interactions in real time. In contrast, multi-photon microscopy
allows for deep tissue imaging and tracking of multiple cell types in intact
tissues over time. Here, we describe a protocol for in vivo detection of IL-4
expressing Tfh cells in an explanted popliteal lymph node by multi-photon
microscopy. The dynamics of Tfh cell motility and their interactions with FDC
networks in the GCs were analyzed.
PMID- 29956156
TI - Imaging Precision-Cut Lung Slices to Visualize Leukocyte Localization and
Trafficking.
AB - Pulmonary dendritic cells (DCs) are potent antigen-presenting cells that can
activate both naive and memory/effector T cells. However, very little is known of
how movements and localization of DCs contribute to these events. To study this,
we have developed new procedures that combine precision-cut lung slices with cell
staining using fluorescently tagged antibodies to detect individual cell types.
In this chapter, we describe these methods in detail and show how they can be
used to study the localization of not only DCs but also other leukocytes of
interest, as well as structural cells within the lung.
PMID- 29956157
TI - Study of IgE-Producing B Cells Using the Verigem Fluorescent Reporter Mouse.
AB - Immunoglobulin E (IgE) is the least abundant antibody isotype in mammalians, yet
it plays a critical role in allergy and asthma. IgE-producing (IgE+) B cells are
rare and difficult to detect, which have hindered progress to understand their
generation and differentiation. Recently developed new fluorescent IgE reporter
mice have enabled better understanding of the biology of IgE+ B cells. We here
describe the usage of the Verigem IgE reporter mouse to study IgE+ B cells and
plasma cells by flow cytometry and microscopy.
PMID- 29956158
TI - Chromatin Preparation from Murine Eosinophils for Genome-Wide Analyses.
AB - Dynamic gene expression is a major mechanism that directs hematopoietic lineage
commitment and differentiation. Recent advances have revealed an association
between chromatin signatures and functional genetic sequences such that these
chromatin signatures can be used to predict regulatory elements such as enhancers
that may direct lineage differentiation. Our understanding of the genetic
elements that regulate eosinophil development is very limited, likely due to the
technical challenges in working with a rare complex cell. Herein, we describe
protocols to sort mature eosinophils from the bone marrow of mice and to prepare
chromatin that can be used for ChIP studies for genome-wide mapping of histone
marks and transcription factors in mature eosinophils. Comprehensive epigenomic
profiling during critical stages in eosinophil development will ultimately aid in
defining the gene regulatory networks necessary to regulate eosinophil
production.
PMID- 29956159
TI - A Sensitive and Integrated Approach to Profile Messenger RNA from Samples with
Low Cell Numbers.
AB - Transcriptomic profiling by RNA sequencing (RNA-Seq) represents the preferred
approach to measure genome-wide gene expression for understanding cellular
function, tissue development, disease pathogenesis, as well as to identify
potential biomarkers and therapeutic targets. For samples with small cell
numbers, multiple methods have been described to increase the efficiency of
library preparation and to reduce hands-on time and costs. This chapter reviews
our approach, which combines flow cytometry and the most recent high-resolution
techniques to perform RNA-Seq for samples with low cell numbers as well as for
single-cell samples. Our approach reduces technical variability while increasing
sensitivity and efficiency. Thus, it is well-suited for large-scale gene
expression profiling studies with limited samples for basic and clinical studies.
PMID- 29956160
TI - An Integrated and Semiautomated Microscaled Approach to Profile Cis-Regulatory
Elements by Histone Modification ChIP-Seq for Large-Scale Epigenetic Studies.
AB - Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) is the preferred
approach to map histone modifications and identify cis-regulatory DNA elements
throughout the genome. Multiple methods have been described to increase the
efficiency of library preparation and to reduce hands-on time as well as costs.
This review describes detailed steps to perform cell fixation, chromatin
shearing, immunoprecipitation, and sequencing library preparation for a batch of
48-96 samples with small cell numbers. The protocol implements a semiautomated
platform to reduce technical variability and improve signal-to-noise ratio as
well as reduce hands-on time, thus allowing large-scale epigenetic studies of
clinical samples with limited cell numbers.
PMID- 29956161
TI - Library Preparation for ATAC-Sequencing of Mouse CD4+ T Cells Isolated from the
Lung and Lymph Nodes After Helminth Infection.
AB - Although conventional methods such as MNase-seq, DNase-seq, and ChIP-seq have
been used effectively to assess chromatin and locus accessibility at the genome
level, these techniques generally require large numbers of input cells. As such,
much of what we understand in terms of epigenetic regulation and locus
accessibility in CD4+ T cell subsets comes from in vitro culture systems, which
allow for the production of large numbers of polarized T cells. However,
obtaining such numbers directly ex vivo from tissues of individual mice is
difficult. Here we describe a method combining cytokine reporter mice and Assay
for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq)
to identify genome wide locus accessibility in a small number of cytokine
expressing CD4+ T cells. This method takes you from cell isolation to library
generation and quality control to query. Because the Il4 and Ifng loci are
reciprocally regulated in polarized CD4+ T cell subsets (Th1 vs. Th2), we
investigated the ability of this approach to identify transposase integration in
both IL-4- and IFN-gamma-expressing CD4+ T cells isolated directly from the lung
and lymph nodes after helminth infection.
PMID- 29956163
TI - The Use of Biodegradable Nanoparticles for Tolerogenic Therapy of Allergic
Inflammation.
AB - Antigen-specific tolerance is the ultimate aim of treatment of allergic diseases.
Here, we describe methods for the use of biodegradable nanoparticles to safely
induce tolerance for the prevention and treatment of allergic inflammation in
mice. Antigen is either conjugated to the surface of carboxylated poly(lactide-co
glycolide) (PLG) or encapsulated within PLG nanoparticles, and the resulting
antigen-associated nanoparticles are then washed prior to intravenous injection
to inhibit antigen-specific allergic immune responses.
PMID- 29956164
TI - Assessing the Mouse Intestinal Microbiota in Settings of Type-2 Immune Responses.
AB - The microbial communities that reside within the mammalian host play important
roles in the development of a robust host immune system. With the advent of
sequencing technology and barcoding strategy of the bacterial 16S ribosomal RNA
(rRNA) gene, microbiota studies are becoming more economical but also more
important in many immunology studies. Here, we described a representative study
protocol to characterize how the microbiota changes during an intestinal helminth
infection, with emphasis on subtle aspects of the experimental design that are
critical for data interpretation.
PMID- 29956162
TI - Identification of Functionally Relevant microRNAs in the Regulation of Allergic
Inflammation.
AB - Transgenic methods to manipulate CD4 T lymphocytes in vivo via forced expression
of TCR transgenes and targeted "knockout" of individual genes by Cre-lox
technology are fundamental to modern immunology. However, efforts to scale up
functional analysis by modifying expression of larger numbers of genes in T cells
ex vivo have proven surprisingly difficult. Early RNA interference experiments
achieved successful small RNA transfection by using very high concentrations of
short-interfering RNA (siRNA) [1], but primary T cells are generally resistant to
standard electroporation, cationic liposome-, and calcium phosphate-mediated
transfection methods. Moreover, although viral vectors can successfully introduce
DNA fragments of varying length, expression of these constructs in primary T
cells is low efficiency and the subcloning process laborious. In this context,
the relatively recent discovery of dozens of highly expressed microRNAs (miRNAs)
in the immune system provides both an opportunity and a new challenge [2, 3]. How
can we query the miRNAome of a cell to assign particular roles to individual
miRNAs? Here, we describe an optimized technique for efficient and reproducible
transfection of primary mouse CD4 T cells in vitro with synthetic miRNA mimics.
PMID- 29956165
TI - The Use of CRISPR-Cas9 Technology to Reveal Important Aspects of Human Airway
Biology.
AB - The CRISPR-Cas9 technology is a powerful tool that enables site-specific genome
modification (gene editing) and is increasingly used in research to generate gene
knockout or knock-in in a variety of cells and organisms. This chapter provides a
brief overview of this technology and describes a general methodology applicable
to human airway biology research.
PMID- 29956166
TI - A Consistent Method to Identify and Isolate Mononuclear Phagocytes from Human
Lung and Lymph Nodes.
AB - Mononuclear phagocytes (MP) consist of macrophages, dendritic cells (DCs), and
monocytes. In all organs, including the lung, there are multiple subtypes within
these categories. The existence of all these cell types suggest that there is a
clear division of labor and delicate balance between the MPs under steady state
and inflammatory conditions. Although great strides have been made to understand
MPs in the mouse lung, and human blood, little is known about the MPs that exist
in the human lung and lung-draining lymph nodes (LNs), and even less is known
about their functional roles, studies of which will require a large number of
sorted cells. We have comprehensively examined cell surface markers previously
used in a variety of organs to identify human pulmonary MPs. In the lung, we
consistently identify five extravascular pulmonary MPs and three LN MPs. These
MPs were present in over 100 lungs regardless of age or gender. Notably, the
human blood CD141+ DCs, as described in the literature, were not observed in non
diseased lungs or their draining LNs. In the lung and draining LNs, expression of
CD141 was only observed on HLADR+ CD11c+ CD14+ extravascular monocytes (often
confused in the LN as resident DCs based on the level of HLADR expression and
mouse LN data). In the human lung and LNs there are at least two DC subtypes
expressing HLADR, DEC205 and CD1c, along with circulating monocytes that behave
as either antigen-presenting cells or macrophages. Furthermore, we demonstrate
how to distinguish between alveolar macrophages and interstitial macrophage
subtypes. It still remains unclear how the human pulmonary MPs identified here
align with mouse MPs. Clearly, we are now past the stage of cell surface marker
characterization, and future studies will need to move toward understanding what
these cell types are and how they function. Our hope is that the strategy
described here can help the pulmonary community take this next step.
PMID- 29956167
TI - Organoid Cultures for Assessing Intestinal Epithelial Differentiation and
Function in Response to Type-2 Inflammation.
AB - During helminth infection of the gastrointestinal tract, a complex Type-2
inflammatory response involving immunological and mucosal components is mounted
to clear the infection and reestablish a physiologically normal state. This
response is characterized by the secretion of key interleukins, which impact
epithelial lineage allocation and drive tuft and goblet cell hyperplasia to lead
to eventual clearance of parasitic organisms. While there have been advances
toward understanding Type-2 inflammatory responses in the intestine, detailed
cellular and molecular mechanisms of epithelial responses to general inflammation
and specific inflammatory cytokines remain to be explored. Intestinal organoids
represent a physiologically relevant in vitro model to study how Type-2
inflammation impacts stem cell maintenance and differentiation and offer a new
approach for investigators to test compounds that modulate mechanisms involved in
worm clearance. The methods described in this chapter include: (1) intestinal
crypt and single cell isolation; (2) organoid culture and cytokine treatment, as
well as methods for downstream organoid analyses; (3) gene expression analysis by
qRT-PCR; (4) protein analysis by western blot, immunohistochemistry, and
florescence-activated cell sorting; and (5) organoid self-renewal by serial
passaging.
PMID- 29956168
TI - Utilization of Air-Liquid Interface Cultures as an In Vitro Model to Assess
Primary Airway Epithelial Cell Responses to the Type 2 Cytokine Interleukin-13.
AB - The airway epithelium lines the respiratory tract and provides the primary
protective barrier against inhalational insults including toxic environmental
substances and microorganisms. The airway epithelium also plays a critical role
in regulating airway immune responses. The airway epithelial response to the type
2 cytokine, interleukin-13 (IL-13), is critical to airway inflammation, mucus
production, and airway hyperresponsiveness present in asthma. Relevant primary
cell models of the human airway epithelium are needed to investigate the biology
of IL-13-mediated airway epithelial effects. Here, we describe the generation of
a differentiated mucociliary human airway epithelium using an in vitro air-liquid
interface (ALI) culture model system. We also describe methods to stimulate this
culture model with IL-13 and harvest cells and biomolecules to interrogate
cellular and molecular aspects of the airway epithelial IL-13 response.
PMID- 29956169
TI - Challenges in Developing Protein Secretion Assays at a Single-Cell Level.
AB - In addition to direct physical interactions between/among cells, the secretion of
humoral factors from living cells is a critical process for cell-cell
communications. A well-known extracellular signaling event is mediated by immune
cell cytokines/chemokines. Because cell-cell communication is crucial in immune
cell sociology, protein secretion assays first attracted a broad range of
immunology interests. Now that we have entered an era of systems biology, cell
cell interactions mediated by secreted molecules should be revisited to
understand the dynamics and homeostasis of the cell society as a whole. Of more
importance, recent advances in detection and microfluidics technologies enable us
to monitor protein secretion in real time rather than as a snapshot from the
past, which gives us an opportunity to more deeply understand the logic of
mammalian cell sociology. This chapter reviews the recent progress in and future
direction of protein secretion assays, particularly from a mammalian cell
sociology viewpoint.
PMID- 29956170
TI - Mastering the Computational Challenges of Elispot Plate Evaluation.
AB - Much has been written about Elispot and how to optimally run the assay for a wide
variety of applications. But only a limited number of articles exist addressing
the analysis step, the plate evaluation. Comparing that fact with the vast amount
of analysis advise available for other single cell immune assay, for example,
intracellular cytokine staining, the overall impression may be that Elispot
evaluation is just simple enough to not require extensive elaboration and
guidance. At first thought this appears reasonable because how difficult can it
be counting colored spots on a white background. In addition, automated Elispot
readers were already introduced more than 20 years ago (Herr et al., J Immunol
Methods 203, 141-152, 1997), easing the strenuous load of manual counting and
providing means to decrease the subjectivity in Elispot analysis. Just shortly
thereafter however, the first report was published about the subjectivity and
operator-dependency of plate evaluation even when using automated reader systems
(Janetzki et al., J Immunol Methods 291, 175-183, 2004). Later, the plate
evaluation was identified as a main factor causing variability in Elispot
results, triggering the inclusion of recommendations on handling of artifacts and
the audits of plate reading results in the Initial Elispot Harmonization
guidelines (Janetzki et al., Cancer Immunol Immunother 57, 303-315, 2008; Britten
et al., Cancer Immunol Immunother 57, 289-302, 2008). In follow-up, a large
international study with 75 laboratories was conducted to address the current
approaches taken to evaluate Elispot plates and to establish consensus guidelines
for plate evaluation (Janetzki et al., Nat Protoc 10, 1098-1115, 2015). This
article addresses the special challenges of plate evaluation, gives explanations
for unusual observation, and provides overall recommendations on how to work
through the labyrinth of available algorithms and reader settings to obtain
reliable Elispot data.
PMID- 29956171
TI - Essential Controls for ELISpot Assay.
AB - Nonspecific staining in ELISpot assay is a major obstacle in accurate
quantification of experimental data. The appearance of nonspecific spots may be
caused by different factors including cell- and immunoassay-related issues. In
our study, we have shown that nonspecific spots can result from either cells or
their debris sticking to the membranes in ELISpot plates, as well as by
impurities in wash buffers and precipitation of aggregated detection antibodies.
Although there is a growing interest in using Fluorospot assays allowing for
simultaneous detection of multiple cell-secreted proteins, it appears that these
fluorescence assays are more susceptible to developing nonspecific profiles
resembling specific spots. In this chapter, we outline necessary ELISpot controls
that need to be employed to tell the difference between bona fide spots vs.
stained artifacts.
PMID- 29956172
TI - Automatic Search of Spots and Color Classification in ELISPOT Assay.
AB - Accuracy of spot detection and classification plays a critical role in the
analysis of ELISPOT data. Differences in staining intensities of spots and their
morphological variations make it difficult developing a reliable software
application. An image recognition method allowing the automatic detection and
classification of round objects (spots) on ELISPOT images independently of the
registration conditions was developed. The emphasis is done on objects of
elliptical shape, which is typical for a wide range of spots. It can be analyzed
by both monochrome and a dual-color version of our software. The method of
subdivision of objects into groups is also described which is based on color
attributes of spots.
PMID- 29956173
TI - Four Color ImmunoSpot(r) Assays for Identification of Effector T-Cell Lineages.
AB - Single color IFN-gamma ELISPOT assays have evolved as a highly sensitive T cell
immune monitoring platform. By detecting individual T cells that secrete IFN
gamma in response to antigen exposure, these assays permit the measurement of the
frequency of antigen-specific T cells among white blood cells. These assays
therefore are well suited to assess clonal expansions, that is, whether a (Th1) T
cell response has been induced to an antigen in a test subject. Single color IFN
gamma ELISPOT assays are not suited, however, to provide information on the
Th2/Th17 quality of the T cell response, nor do they provide insights into the
differentiation state of CD8 cells. Recently it has been established that co
expression profiles of IL-2, TNF-alpha, and granzyme B along with IFN-gamma
permit to identify CD8 cell subpopulations. Naive CD8 cells, central CD8 memory
cells, CD8 terminal effector cells, polyfunctional CD8 cells, stem-cell like CD8
memory cells, dysfunctional- and senescent CD8 cells all differ in the extent
they produce these molecules upon antigen re-encounter. We therefore have
developed, and introduce here, a four color T cell ELISPOT assay in which the co
expression levels of IFN-gamma, IL-2, TNF-alpha, and granzyme B can be
established for individual antigen-specific CD8 cells, thereby identifying the
activation/differentiation state of these cells.
PMID- 29956174
TI - Detection of Cross-Reactive B Cells Using the FluoroSpot Assay.
AB - B cell ELISpot enables a sensitive analysis of antigen-specific B cells at the
single cell level but is limited to the analysis of reactivity with a single
antigen. By reversing the B cell ELISpot and using anti-IgG capture antibodies
instead of coated antigen, the specificity of antibodies secreted by B cells can
be defined using soluble tagged antigen for detection. When combining this
approach with fluorescent detection of the antigen in a B cell FluoroSpot assay,
reactivity with multiple antigens can be defined. In the protocol described
herein, splenocytes from a mouse immunized with an antigen were analyzed for
their reactivity with the antigen used for immunization and for cross-reactivity
with a different but structurally related antigen. Using this assay, we found
that at least 15% of the B cells displayed detectable cross-reactivity. B cell
FluoroSpot utilizing multiple antigens provides a tool for a single-cell analysis
of B cell cross-reactivity, for example, with variable and polymorphic antigens
found in various pathogens; or analysis of other types of immune responses where
analysis of cross-reactivity is of interest. It is also possible to
simultaneously analyze B cell reactivity to completely different antigens.
PMID- 29956175
TI - Multiplex ImmunoSpot(r) Assays for the Study of Functional B Cell Subpopulations.
AB - B cells mediate humoral immunity by producing antibody molecules, but they also
participate in innate and acquired immune functions via the secretion of effector
molecules such as cytokines, chemokines, and granzyme. B cell subpopulations
releasing such effector molecules have been implicated in immunobiology and a
number of diseases.Unlike antigen-specific T cells that can be identified by
multimer staining, and then counter-stained to define T cell subpopulations,
antigen-specific B cells cannot be detected by flow cytometry. Staining antigen
specific B cells with labeled antigen, in large, has been unsuccessful. Instead,
antigen-specific B cells can be and are commonly studied by ELISPOT. In the
ELISPOT approach, the B cell is identified via the antibody that it secretes
being captured on a membrane by the antigen itself. Should it be feasible to
measure simultaneously antibody production and the secretion of other secretory B
cell products, it would then be possible to identify B cell subpopulations that
co-express effector molecules. Here we introduce multiplex ELISPOT assays in
which measurements of antibody secretion are combined with the detection of
Granzyme B, IL-6, IL-10, IFN-gamma, and TNF-alpha. Such multiplex assays will
help define effector B cell subpopulations, as well as the understanding of their
role in health and disease.
PMID- 29956176
TI - Detecting all Immunoglobulin Classes and Subclasses in a Multiplex 7 Color
ImmunoSpot(r) Assay.
AB - Antibody molecules in peripheral blood have a relatively short half-life of
roughly 20 days, and therefore their persistence in the serum depends on
continuous replenishment by plasma cells. Serum antibody titers are thus indirect
and unreliable indicators of immunological memory. In contrast, memory B cells
persist in peripheral blood for decades, and enumerating these cells provides
direct evidence of having developed an immune response to a given antigen.
ELISPOT is an ideal research tool for enumerating antigen-specific memory B
cells. Traditionally, B cell ELISPOT assays have been performed for detecting a
single class of immunoglobulin (Ig), using a single colorimetric substrate. For
comprehensive monitoring of B cell memory, however, all immunoglobulin classes
and subclasses need to be assessed. Thus, seven single color assays would need to
be performed to measure the numbers of antigen-specific B cells producing IgM,
IgA, IgE, IgG1, IgG2, IgG3, and IgG4. We report here the development of a
multiplex seven color B cell ImmunoSpot(r) assay in which the number of antigen
specific B cells can be established simultaneously for all major antibody classes
and subclasses, requiring the PBMC, antigen, and labor corresponding to a single
color assay.
PMID- 29956177
TI - Multiplexing T- and B-Cell FLUOROSPOT Assays: Experimental Validation of the
Multi-Color ImmunoSpot(r) Software Based on Center of Mass Distance Algorithm.
AB - Over the past decade, ELISPOT has become a highly implemented mainstream assay in
immunological research, immune monitoring, and vaccine development. Unique single
cell resolution along with high throughput potential sets ELISPOT apart from flow
cytometry, ELISA, microarray- and bead-based multiplex assays. The necessity to
unambiguously identify individual T and B cells that do, or do not co-express
certain analytes, including polyfunctional cytokine producing T cells has
stimulated the development of multi-color ELISPOT assays. The success of these
assays has also been driven by limited sample/cell availability and resource
constraints with reagents and labor. There are few commercially available test
kits and instruments available at present for multi-color FLUOROSPOT. Beyond
commercial descriptions of competing systems, little is known about their
accuracy in experimental settings detecting individual cells that secrete
multiple analytes vs. random overlays of spots. Here, we present a theoretical
and experimental validation study for three and four color T- and B-cell
FLUOROSPOT data analysis. The ImmunoSpot(r) Fluoro-XTM analysis system we used
includes an automatic image acquisition unit that generates individual color
images free of spectral overlaps and multi-color spot counting software based on
the maximal allowed distance between centers of spots of different colors or
Center of Mass Distance (COMD). Using four color B-cell FLUOROSPOT for IgM, IgA,
IgG1, IgG3; and three/four color T-cell FLUOROSPOT for IL-2, IFN-gamma, TNF
alpha, and GzB, in serial dilution experiments, we demonstrate the validity and
accuracy of Fluoro-XTM multi-color spot counting algorithms. Statistical
predictions based on the Poisson spatial distribution, coupled with scrambled
image counting, permit objective correction of true multi-color spot counts to
exclude randomly overlaid spots.
PMID- 29956178
TI - Multi-Color FLUOROSPOT Counting Using ImmunoSpot(r) Fluoro-XTM Suite.
AB - Multi-color FLUOROSPOT assays for simultaneous detection of several T-cell
cytokines and/or classes/sub-classes of immunoglobulins secreted by B cells have
recently become a major new avenue of development of ELISPOT technology. Advances
in assay techniques and the availability of commercial test kits stimulated
development of multi-color FLUOROSPOT data analysis platforms. The ImmunoSpot(r)
Fluoro-XTM Software Suite was developed by CTL as an integrated data acquisition,
analysis, and management solution for automated high-throughput processing of
multi-color T- and B-cell FLUOROSPOT assay plates. The Fluoro-XTM software
counting module is based on SmartSpotTM/AutoGateTM technologies and utilizes
CTL's Center of Mass Distance algorithm for the detection of multi-color spots.
The Fluoro-XTM software provides an objective, user error-free means for
analyzing multi-color FLUOROSPOT data. An integrated quality control module, with
optional GLP and CFR Part 11 compliant package and role-based security, enables
data validation, review, and approval with complete audit trails. The extensive
multi-format data output and presentation capabilities of the Fluoro-XTM software
allow further analysis of FLUOROSPOT data using any commercial flow cytometry
software and facilitate the generation of professional reports and presentation.
In this article, we present a detailed step-by-step workflow for the analysis of
a human four-color IFN-gamma, IL-2, TNF-alpha, and GzB antigen-specific T-cell
assay using the Fluoro-X Software Suite.
PMID- 29956179
TI - B-Cell ELISpot Assay to Quantify Antigen-Specific Antibody-Secreting Cells in
Human Peripheral Blood Mononuclear Cells.
AB - Peripheral blood is commonly used to assess the cellular and humoral immune
responses in clinical studies. It is a convenient sample to collect for
immunological research as compared to the surgically excised and biopsied
lymphoid specimens. To determine the functional status of immune system from
peripheral blood, the enzyme-linked immunospot (ELISpot) assay is a popular
method of choice owing to its high sensitivity, great accuracy, and easy
performance. The ELISpot allows detection and quantification of cellular
functionality at the single-cell level. Therefore, ELISpot assay is commonly
applied to detect cytokines and cytotoxic granules released from T cells as well
as to measure antibodies secreted from B cells. Because the ELISpot assay has
been increasingly used for evaluation of the vaccine efficacy in clinical trials,
standardization and reproducibility are crucial to minimize assay variability
amongst samples from different sources. Here we introduce methods to isolate
human peripheral blood mononuclear cells (PBMCs) for quantification of the
antigen-specific antibody-secreting cells using the ELISpot assay.
PMID- 29956180
TI - Identification of Novel Mycobacterial Targets for Murine CD4+ T-Cells by IFNgamma
ELISPOT.
AB - Enzyme-linked immunospot (ELISPOT) is an assay used to detect secretion of
cytokines from immune cells. The resolution and sensitivity of ELISPOT allow for
the detection of rare T cell specificities and small quantities of molecules
produced by individual cells. In this chapter, we describe an epitope screening
method that uses CD4+ T cell ELISPOT assays to identify specific novel
mycobacterial antigens as potential vaccine candidates. In order to screen a
large number of candidate epitopes simultaneously, pools of predicted MHC class
II peptides were used to identify mycobacterial specific CD4+ T cells. Using this
method, we identified novel mycobacterial antigens as vaccine candidates.
PMID- 29956181
TI - ELISPOT-Based "Multi-Color FluoroSpot" to Study Type-Specific and Cross-Reactive
Responses in Memory B Cells after Dengue and Zika Virus Infections.
AB - Co-circulation and re-emergence of antigenically related viruses such as dengue
(DENV), Zika (ZIKV), and yellow fever (YF) in the Americas has brought a sense of
urgency in the field to further define the genesis and to more fully describe the
immune response. The recent explosive epidemics of Zika in the Americas and the
co-circulation of ZIKV with the phylogenetically similar DENV has raised
important questions and concerns regarding the role of cross-reactive immunity in
protection and potential enhancement of severity of subsequent ZIKV or DENV
infections in pre-immune individuals and the safety of vaccines against both
viruses in endemic populations. Antibodies are a critical part of the immune
response for clearing flavivirus infections, but the role of pre-existing
antibodies in protection or enhancement of subsequent infection and disease with
closely related viral species and strains is still not fully understood. We have
developed a novel Multi-Color FluoroSpot (MCF) assay based on our ELISPOT-derived
assay, previously designated the Quad-color FluoroSpot (QCF), in order to study
the development of type-specific versus cross-reactive responses within the B
cell pool of Zika virus (ZIKV)- and/or dengue virus (DENV)-infected patients. The
QCF is based on a panel of four fluorescent Qdots, each conjugated to a
monoclonal antibody specific to one of the four DENV serotypes; now we have
included a fifth color (Qdot) for ZIKV to enable analysis of the specificity
versus cross-reactivity of B cell populations at a single-cell level for all four
DENV serotypes and ZIKV. This novel assay allows us to analyze unique human
samples from long-term studies of dengue and Zika in Nicaragua to investigate the
nature of B cell/antibody responses and their role in pathogenesis and/or
protection in secondary flavivirus infections and could have important
implications for vaccine development for Zika and dengue.
PMID- 29956182
TI - Cultured ELISpot Assay to Investigate Dengue Virus Specific T-Cell Responses.
AB - The cultured Enzyme-Linked ImmunoSpot (ELISpot) assay is a functional T cell
assay, which is commonly used to assess virus-specific T cell responses. The use
of an in vitro expansion step before the ELISpot distinguishes such "cultured"
ELISpots from "ex vivo" ELISpots. Cultured ELISpots have the advantage that lower
frequency responses can be analyzed compared to ex vivo ELISpots, but do carry
the associated potential distortions of the expansion phase. Cultured ELISpot
assays are of value to determine silent and symptomatic transmission of the
Dengue virus (DENV) in the community and to identify the correlates of a DENV
specific protective immune response. We have evaluated T cell responses to the
DENV using cultured ELISpot assays with serotype-specific T cell epitopes to
determine past infecting dengue virus (DENV) serotypes. The peptides used in this
assay do not cross react with the Japanese encephalitis virus nor other
flaviviruses. Therefore, this assay is likely to be useful in determining the
past infecting DENV serotype in immune-epidemiological studies and in dengue
vaccine trials.
PMID- 29956183
TI - Ex Vivo ELISpot Assay to Investigate Dengue Virus Specific T-Cell Responses.
AB - Enzyme-Linked ImmunoSpot (ELISpot) assay is a functional T cell assay which is
commonly used to assess virus-specific T cell responses. We have used ex vivo
ELISpot responses to investigate the role of dengue virus (DENV) specific T cells
in acute dengue infection, to evaluate their role in possible disease
pathogenesis and protection. We have also used ex vivo IFNgamma ELISpot assays to
determine the functionality of T cell responses in those who were previously
naturally infected with dengue and we have determined the frequency of DENV
specific memory T cells responses in relation to past clinical disease severity.
We have also evaluated ELISpot supernatants to study multiple cytokines produced
by DENV-specific T cells, in instances where there are fewer numbers of cells
available for multiple assays. ELISpot assays are likely to be helpful in large
scale dengue vaccine trials to assess the immunogenicity of the vaccines.
PMID- 29956184
TI - Ex Vivo ELISpot Assay to Investigate iNKT Cell Responses in Acute Dengue
Infection.
AB - T cell receptors of the invariant Natural Killer T (iNKT) cells are downregulated
with antigen stimulation. Therefore, identification of this cell population with
flow cytometry in functionality studies is challenging. iNKT cells are known to
produce both Th1 and Th2 cytokines immediately upon antigen stimulation.
Therefore, we have used an ELISpot assay to determine the production of IFN-gamma
and IL-4 after stimulation with KRN7000, which has shown to bind to CD1d
molecules and activate iNKTs in a similar fashion as alpha-GalCer. In this study,
we observed that peripheral iNKT cells in patients with acute dengue show
distinct production of IFN-gamma, but not IL-4 with KRN7000 stimulation.
PMID- 29956185
TI - Dendritic Cell-Based ELISpot Assay for Assessing T-Cell IFN-gamma Responses in
Human Peripheral Blood Mononuclear Cells to Dengue Envelope Proteins.
AB - Dengue envelope (E) protein is a dominant antigen for vaccine development and E
based vaccines have shown partial or full protection against live-virus challenge
in non-human primates. Generally, T cell responses can be investigated with
peptides. However, hundreds of over-lapping peptides need to be synthesized to
cover the whole sequence of a protein, which brings the cost up to a much higher
level than purchasing a protein. We have developed an enzyme-linked immunospot
(ELISpot) assay that uses intact E proteins instead of peptides for assessing IFN
gamma (IFN-gamma) responses. The assay relies on professional antigen presenting
cells, dendritic cells, to process and present the E proteins to stimulate T
cells.Peripheral blood mononuclear cells (PBMCs) from dengue-exposed and naive
subjects were selected for the assay development. IFN-gamma production ranged
from 53 to 513 spot forming units (SFUs) and 0-45 SFUs per million PBMCs in
dengue-exposed and naive subject groups, respectively. The assay allowed
quantification of E-specific IFN-gamma secreting memory T cells in subjects 9
years after exposure to a live-attenuated virus vaccine and live-virus challenge.
Our results suggest that the dendritic cell-based IFN-gamma assay is a useful
tool for assessing immunological memory for clinical research.
PMID- 29956186
TI - Utilization of Feline ELISpot to Evaluate the Immunogenicity of a T Cell-Based
FIV MAP Vaccine.
AB - The prototype and the commercial dual-subtype feline immunodeficiency virus (FIV)
vaccines conferred protection against homologous FIV strains as well as
heterologous FIV strains from the vaccine subtypes with closely related envelope
(Env) sequences. Such protection was mediated by the FIV neutralizing antibodies
(NAbs) induced by the vaccines. Remarkably, both prototype and commercial FIV
vaccines also conferred protection against heterologous FIV subtypes with highly
divergent Env sequences from the vaccine strains. Such protection was not
mediated by the vaccine-induced NAbs but was mediated by a potent FIV-specific T
cell immunity generated by the vaccines (Aranyos et al., Vaccine 34: 1480-1488,
2016). The protective epitopes on the FIV vaccine antigen were identified using
feline interleukin-2 (IL-2) and interferon-gamma (IFNgamma) ELISpot assays with
overlapping FIV peptide stimulation of the peripheral blood mononuclear cells
(PBMC) from cats immunized with prototype FIV vaccine. Two of the protective FIV
peptide epitopes were identified on FIV p24 protein and another two protective
peptide epitopes were found on FIV reverse transcriptase. In the current study,
the multiple antigenic peptides (MAPs) of the four protective FIV peptides were
combined with an adjuvant as the FIV MAP vaccine. The laboratory cats were
immunized with the MAP vaccine to evaluate whether significant levels of vaccine
specific cytokine responses can be generated to the FIV MAPs and their peptides
at post-second and post-third vaccinations. The PBMC from vaccinated cats and non
vaccinated control cats were tested for IL-2, IFNgamma, and IL-10 ELISpot
responses to the FIV MAPs and peptides. These results were compared to the
results from CD4+ and CD8+ T-cell proliferation to the FIV MAPs and peptides.
Current study demonstrates that IL-2 and IFNgamma ELISpot responses can be used
to detect memory responses of the T cells from vaccinated cats after the second
and third vaccinations.
PMID- 29956187
TI - Detection and Quantification of Influenza A/H1N1 Virus-Specific Memory B Cells in
Human PBMCs Using ELISpot Assay.
AB - Immune response following subsequent encounter of viruses (and vaccines) relies
largely on the pool and frequencies of antigen-specific memory B cells. In
addition to antibody titers, the reliable measurement of these cells in human
blood (peripheral blood mononuclear cells/PBMCs or purified B cells) provides
valuable information on the preparedness of the adaptive immune system to respond
to infection or vaccines, and potentially supports the discovery of new
quantitative correlates of protection. The Mayo Clinic Vaccine Research Group has
developed and optimized a high-throughput ELISPOT-based assay for the
quantification of influenza A/H1N1 virus-specific memory B cells in human PBMCs.
Here, we present the materials and detailed methodology for using this assay on
cryopreserved cells for the measurement of recall humoral immunity readiness
(antigen-specific memory B cell frequencies) after influenza vaccination. This
assay could be readily adapted to other influenza virus strains and other
respiratory viruses and vaccines for use in systems biology and larger population
based studies.
PMID- 29956188
TI - Towards a Full Automation of the ELISpot Assay for Safe and Parallelized
Immunomonitoring.
AB - The ELISpot assay, as a sensitive and specific method, enables the detection of
cytokines for immunological purposes and in vaccine development. Here we describe
the successful transfer of the manual procedure to a commercially available
automated liquid handling platform, based on the work described in Neubauer et
al. (Cytotechnology 69:57-73, 2017). Different kinds of technical issues (dead
volume reduction, instrumental handling limitations, liquid class improvement)
have been solved and biological effects (reagents concentration, selectivity
tests, dispensing way, etc.) have been controlled during the implementation
process. At the end a maximum of 6% mean delta difference and a lower mean
dispersion than the manual assay were reached as well as a turnaround time of
four to six times higher than the manual process.
PMID- 29956189
TI - One-Carbon Metabolism and Lipid Metabolism in DOHaD.
AB - The predisposing factors to lifestyle-associated diseases are established in the
early period of life with underlying gene-environment interaction. Epigenetics is
a chemical modification-based genetic mechanism that is affected by various
nutritional factors. One-carbon metabolism is a metabolic system associated with
methyl residue that is supplied from folic acid. Therefore, from the epigenetic
point of view, proper intake of folic acid is important for pregnant women not
only to prevent congenital abnormalities such as neural tube defect but also to
prevent various adult disorders of the offspring. Dyslipidemia is an important
risk factor of coronary heart disease, and epidemiological studies on Dutch
winter famine, Jewish holocaust survivors, and Chinese famine suggested that
prenatal malnutrition was associated with the dyslipidemia. Recent animal studies
revealed that malnutrition in utero causes an epigenetic change in the Pparalpha
gene, which accelerates the activity of delta-6 desaturase and delta-5
desaturase, that potentially induces dyslipidemia in adulthood. It has been known
that overnutrition also increased the risk of cardiovascular diseases. Recent
animal studies revealed that high-fat diet increased DNA methylation in the
promoter region of delta-6 desaturase gene (Fads 2) that downregulates the gene
expression in the arterial smooth muscle, which potentially contributes to
cardiovascular diseases. Taken together, either insufficient or excessive
nutrition alters epigenetic modification of genes that encodes enzymes associated
with lipid metabolism. This altered epigenetic state persists during one's
lifetime, which is potentially involved in noncommunicable diseases in adulthood.
PMID- 29956190
TI - Novel Models of Epigenetic Gene Regulation in the Nutritional Environment.
AB - Epigenetic memories are acquired information included in the chromatin or DNA
such as methylation and histone modifications. Recent studies suggest that
epigenetic memories determine the types of differentiated cells in each tissue.
Moreover, the development of metabolic diseases induced by environmental factors
during development is controlled by epigenetic regulation rather than the genetic
regulation such as DNA sequence-dependent transcriptional regulation. In general,
the demethylation of CpG islands induces histone acetylation, associated changes
from heterochromatin to euchromatin, and enhances transcriptional activation.
Under the classical model of epigenetics, these changes are induced by the
binding of transcriptional factors to cis-elements located on promoter/enhancer
regions and the associated binding of histone acetyl-transferase and the
transcription initiation complex. This model is dependent on epigenetics in the
promoter/enhancer region and is used to explain the induction of genes by
lipophilic nutrients such as vitamin A, vitamin D, and unsaturated fatty acid
metabolites. However, recent studies have demonstrated that epigenetics in the
gene body (transcribed region) also regulate transcription. This novel model
postulates that histone acetylation and bromodomain-containing protein 4, which
contains two bromodomains to bind acetylated histones, on the gene body enhance
transcriptional elongation. Gene expression alterations induced by carbohydrate
signals and changes to energy balance in the body accompanied by the intake of
major nutrients are also regulated by this model. In this section, we introduce
these epigenetic regulations and their relationship with nutrient intake and
discuss the link between epigenetic regulation and the development of metabolic
diseases.
PMID- 29956191
TI - Epigenetic Switching and Neonatal Nutritional Environment.
AB - The hepatic metabolic function changes sequentially during early life in mammals
to adapt to the drastic changes in the nutritional environment. Accordingly,
hepatic fatty acid beta-oxidation is activated after birth to produce energy from
breast milk lipids. De novo lipogenesis is induced upon the onset of oral intake,
when the major nutritional source switches to carbohydrate. However, how a
particular metabolic pathway is activated during the liver maturation is poorly
understood. We found that the expression of glycerol-3-phosphate acyltransferase
1 (GPAT1), a rate-limiting enzyme of de novo hepatic lipogenesis, is
epigenetically regulated in the mouse liver by DNA methylation. In the neonatal
liver, DNA methylation of the GPAT1 gene (Gpam) promoter, which is likely to be
induced by DNA methyltransferase (Dnmt) 3b, inhibited the recruitment of sterol
regulatory element-binding protein-1c (SREBP-1c), whereas in the adult, decreased
DNA methylation resulted in active chromatin conformation, allowing the
recruitment of SREBP-1c. Maternal nutritional environment affects the DNA
methylation status in the Gpam promoter, GPAT1 expression, and triglyceride
content in the liver of the offspring. We also found DNA demethylation and
increased mRNA expression of the fatty acid beta-oxidation genes in the postnatal
mouse liver. The DNA demethylation is specifically induced in the lactation
period. Analysis of mice deficient in the nuclear receptor peroxisome
proliferator-activated receptor alpha (PPARalpha) and maternal administration of
a PPARalpha ligand during the gestation and lactation periods reveals that the
DNA demethylation is PPARalpha-dependent. These findings indicate the gene- and
lifestage-specific DNA demethylation of a particular metabolic pathway in the
neonatal liver to adapt the marked changes in nutritional environment in early
life.
PMID- 29956192
TI - Developmental Origins of Nonalcoholic Fatty Liver Disease (NAFLD).
AB - Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic
syndrome. Its prevalence is currently increasing not only in developed obese
countries but also in developing countries. Recent findings from human cohorts
and animal studies suggest that a nutritional imbalance in the early critical
period is causatively associated with the incidence of NAFLD in later life. Based
on the current theory of the developmental origins of health and disease (DOHaD),
undernourishment and overnourishment in utero are both hypothesized to prime the
predisposition for hepatic fat storage. Current knowledge on the developmental
origins of NAFLD is introduced in this chapter.
PMID- 29956193
TI - Fetal Origins of Hypertension.
AB - Hypertension is a common noncommunicable disease. According to the World Health
Organization, 1.13 billion people were suffering from hypertension in the year
2015. High blood pressure, hypertension, has a multifactorial etiology. Arterial
atherosclerotic changes, systolic or diastolic dysfunction of the heart, and
other noncardiac factors are involved. Epidemiological evidence has revealed that
perinatal growth disturbance elevates the prevalence of hypertension. However,
the specific effects of developmental disturbances on the pathological process of
hypertension are poorly understood. Recently, it has become apparent that the
perinatal period plays many essential roles in cardiovascular development. In
this chapter, we focus on the perinatal development of the cardiovascular system,
especially in murine models. Individual organs, blood, blood vessels, and the
heart show unique growth characteristics during this period. We also introduce
evidence from related clinical studies regarding the developmental origins of
hypertension. Finally, evidence from several animal models is presented to reveal
the effects of developmental disturbance or stress on arterial pathology.
Improving our understanding of both developmental events and the results of
clinical studies will give fresh insight into the fetal origins of hypertension.
PMID- 29956194
TI - Involvement of Noncoding RNAs in Stress-Related Neuropsychiatric Diseases Caused
by DOHaD Theory : ncRNAs and DOHaD-Induced Neuropsychiatric Diseases.
AB - According to the DOHaD theory, low birth weight is a risk factor for various
noncommunicable chronic diseases that develop later in life. Noncoding RNAs
(ncRNAs), including miRNAs, siRNAs, piRNAs, and lncRNAs, are functional RNA
molecules that are transcribed from DNA but that are not translated into
proteins. In general, miRNAs, siRNAs, and piRNAs function to regulate gene
expression at the transcriptional and posttranscriptional levels. Studying ncRNAs
has provided opportunities for new diagnosis and therapeutic knowledge in the
endocrinological and metabolic fields as well as cancer biology. In this review,
we focus on the roles of miRNAs and lncRNAs in the pathophysiology of stress
related neuropsychiatric diseases, which show abnormal blood hormone levels due
to loss of feedback control and/or decreased sensitivity. Numerous recent studies
have begun to unveil the importance of ncRNAs in regulation of stress-related
hormone levels and functions. We summarize the involvement of abnormal ncRNA
expression in the development of stress-related neuropsychiatric diseases based
on the DOHaD theory.
PMID- 29956195
TI - Placental Development and Nutritional Environment.
AB - The placenta is considered to have developed recently in mammalian evolution.
While the fundamental function of the placenta, i.e., providing nutrients and
oxygen to the fetus and receiving waste products, is the same in all mammals, the
morphology of the placenta varies substantially in a species-dependent manner.
Therefore, considerable interest exists in understanding placental development
and function in mammals from a molecular biological viewpoint. Numerous recent
studies have shown that various environmental factors before and during
pregnancy, including nutrition, affect placental formation and function and that
alterations in placental formation and function can influence the developing
fetus and the offspring after birth. To date, the relationship between nutrition
and the placenta has been investigated in several species, various model
organisms, and humans. In this chapter, we discuss the current knowledge of the
placenta and the epigenome and then highlight the effects of nutrition during
pregnancy on the placenta and the fetus and on the offspring after birth.
PMID- 29956197
TI - Preemptive Epigenetic Medicine Based on Fetal Programming.
AB - The developmental origins of health and disease (DOHaD) refers to the concept
that environmental stress during pregnancy alters the programmed fetal
development and subsequently causes disorders, such as cardiovascular and
metabolic diseases, in adulthood. Epigenetics is a gene regulation mechanism that
does not depend on DNA sequence but on chemical modifications of DNA. Several
lines of evidence suggest that environmental stress in the fetal period alters
the epigenetic state of genes, leading to permanent gene dysregulation, which may
be associated with disorders that emerge after birth. Such stresses include
malnutrition, which may be associated with type 2 diabetes, and mental stress,
which may be associated with neurodevelopmental disorders. It has also been
demonstrated that environmental stress-induced epigenetic alterations can be
transmitted to the next generation via disease phenotypes. However, since
epigenetic modification is an internal system based on attachment and detachment
of chemical residues on a DNA sequence, it is reversible and potentially
treatable. In fact, recent studies demonstrated that some drugs and early
interventions are effective at preventing epigenetic disorders. Therefore,
preventive and preemptive medicine is possible for disorders caused by
alterations in programming during fetal and early periods.
PMID- 29956196
TI - Risk of Neurodevelopmental Disease by Paternal Aging: A Possible Influence of
Epigenetic Alteration in Sperm.
AB - Sincethe theory of DOHaD has been thrown in the spotlight, most attention has
focused on environmental effects of the uterus on developing embryos/fetuses.
However, the ontogenesis traces back to gametogenesis. Compared to oogenesis,
spermatogenesis goes through far more cell divisions and is therefore more prone
to genetic variation and epigenetic alterations. This article will mainly discuss
recent findings about the effects of the advanced paternal age on the next
generation, in relation to the onset of psychiatric disorders such as autism
spectrum disorder. We would like to advocate for further exploration on the DOHaD
theory in a wider view.
PMID- 29956198
TI - Prognostic Impact of Extracapsular Lymph Node Invasion on Survival in Non-small
Cell Lung Cancer: A Systematic Review and Meta-analysis.
AB - The extracapsular tumor extension (ECE) of nodal metastasis is an important
prognostic factor in different types of malignancies. However, there is a lack of
recent data in patients with non-small-cell lung cancer (NSCLC). In addition, the
TNM staging system does not include ECE status as a prognostic factor. This
systematic review and meta-analysis has been conducted to summarize and pool
existing data to determine the prognostic role of ECE in patients with lymph node
positive NSCLC. Two authors performed an independent search in PubMed using a
predefined keyword list, without language restrictions with publication date
since 1990. Prospective or retrospective studies reporting data on prognostic
parameters in subjects with NSCLC with positive ECE or with only intracapsular
lymph node metastasis were retrieved. Data were summarized using risk ratios (RR)
for the survival with 95% confidence intervals (CI). The data was analyzed using
Mix 2 (ref: Bax L: MIX 2.0 - Professional software for meta-analysis in Excel.
Version 2.015. BiostatXL, 2016. https://www.meta-analysis-made-easy.com ). There
2,105 studies were reviewed. Five studies covering a total of 828 subjects met
the inclusion criteria and were included in the meta-analysis. Two hundred and
ninety-eight (35.9%) patients were categorized as ECE+, of whom 54 (18.1%)
survived at the end of follow-up. In the ECE-negative group, 257 patients (48.4%)
survived by the end of follow-up. Thus, ECE status is associated with a
significantly decreased survival rate: pooled RR 0.45 (95% CI 0.35-0.59), Q (4) =
4.06, P value = 0.39, and I 2 = 68.00% (95 CI 0.00-79.55%). In conclusion, ECE
has a significant impact on survival in NSCLC patients and should be considered
in diagnostic and therapeutic decisions in addition to the current TNM staging.
Postoperative radiotherapy may be an option in ECE-positive pN1 NSCLC patients.
PMID- 29956199
TI - Effects of Low-Level Laser Therapy in Autism Spectrum Disorder.
AB - The study examined the efficacy of low-level laser therapy, a form of
photobiomodulation, for the treatment of irritability associated with autistic
spectrum disorder in children and adolescents aged 5-17 years. Twenty-one of the
40 participants received eight 5-min procedures administered to the base of the
skull and temporal areas across a 4-week period (test, i.e., active treatment
participants). All the participants were evaluated with the Aberrant Behavior
Checklist (ABC), with the global scale and five subscales
(irritability/agitation, lethargy/social withdrawal, stereotypic behavior,
hyperactivity/noncompliance, and inappropriate speech), and the Clinical Global
Impressions (CGI) Scale including a severity-of-illness scale (CGI-S) and a
global improvement/change scale (CGI-C). The evaluation took place at baseline,
week 2 (interim), week 4 (endpoint), and week 8 (post-procedure) of the study.
The adjusted mean difference in the baseline to study endpoint change in the ABC
irritability subscale score between test and placebo participants was -15.17 in
favor of the test procedure group. ANCOVA analysis found this difference to be
statistically significant (F = 99.34, p < 0.0001) compared to the baseline ABC
irritability subscale score. The study found that low-level laser therapy could
be an effective tool for reducing irritability and other symptoms and behaviors
associated with the autistic spectrum disorder in children and adolescents, with
positive changes maintained and augmented over time.
PMID- 29956200
TI - Virological Situation in Poland in the 2016/2017 Epidemic Season Based on
Sentinel Data.
AB - The influenza Sentinel surveillance system is a source of valuable data about the
dynamics of epidemic seasons in Poland. During the epidemic season 2016/2017,
more than 1,000 samples were examined, of which 48% were positive for influenza
diagnosis. The predominance of influenza A/H3N2/ was confirmed. Influenza B
viruses were noted in only 1% of the samples tested. After the analysis in age
groups, the highest number of positive samples was observed in the group of 26-44
years. Infections caused by influenza-like viruses were confirmed only in 3% of
cases. The Sentinel surveillance system makes it possible to evaluate the spread
of the influenza virus in each epidemic season.
PMID- 29956201
TI - Low-dose radiation cancer risk hypothesis may lead to 'radiophobia'-driven
imaging avoidance?
PMID- 29956203
TI - Epidemiology and Etiologic Associations of Non-alcoholic Fatty Liver Disease and
Associated HCC.
AB - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver
disease in the world and will soon become the number one cause of hepatocellular
carcinoma (HCC), liver transplantation and liver-related mortality. The disease
often occurs in the setting of metabolic conditions such as obesity and type II
diabetes mellitus. These same metabolic drivers are also risk factors for NAFLD
associated HCC which can occur even in the absence of cirrhosis or advanced
fibrosis and appears to be phenotypically different to HCCs arising from other
chronic liver diseases. The frequencies of liver-related events and HCC among
NAFLD patients is low, especially when compared to cardiovascular disease and
extrahepatic malignancies. However, the large denominator of total patients
affected with NAFLD means that these events will impose an enormous clinical and
economic burden on our society. Moreover, this burden is expected to rise further
in the future. Therefore, the global NAFLD epidemic has arrived at our doorstep
and demands our attention.
PMID- 29956202
TI - Introduction.
AB - Obesity is fast becoming a major disorder for mankind. Numerous lifestyle factors
play a role in the rising obesity epidemic, including changes in the diet and the
lack of physical activity. Unfortunately, more than two-thirds of the adult
population in developed countries is considered overweight and more than a third
of them are obese. In addition to the well-publicized association of obesity with
type II diabetes and cardiovascular diseases, emerging evidence indicates that
obesity represents a major risk factor for fatty liver diseases and fatty liver
disease-associated hepatocellular carcinoma (HCC).
PMID- 29956204
TI - Pathogenesis of NASH: How Metabolic Complications of Overnutrition Favour
Lipotoxicity and Pro-Inflammatory Fatty Liver Disease.
AB - Overnutrition, usually with obesity and genetic predisposition, lead to insulin
resistance, which is an invariable accompaniment of nonalcoholic fatty liver
disease (NAFLD). The associated metabolic abnormalities, pre- or established
diabetes, hypertension and atherogenic dyslipidemia (clustered as metabolic
syndrome) tend to be worse for nonalcoholic steatohepatitis (NASH), revealing it
as part of a continuum of metabolic pathogenesis. The origins of hepatocellular
injury and lobular inflammation which distinguish NASH from simple steatosis have
intrigued investigators, but it is now widely accepted that NASH results from
liver lipotoxicity. The key issue is not the quantity of liver fat but the
type(s) of lipid molecules that accumulate, and how they are "packaged" to avoid
subcellular injury. Possible lipotoxic mediators include free (unesterified)
cholesterol, saturated free fatty acids, diacylglycerols, lysophosphatidyl
choline, sphingolipids and ceramide. Lipid droplets are intracellular storage
organelles for non-structural lipid whose regulation is influenced by genetic
polymorphisms, such as PNPLA3. Cells unable to sequester chemically reactive
lipid molecules undergo mitochondrial injury, endoplasmic reticulum (ER) stress
and autophagy, all processes of interest for NASH pathogenesis. Lipotoxicity
kills hepatocytes by apoptosis, a highly regulated, non-inflammatory form of cell
death, but also by necrosis, necroptosis and pyroptosis; the latter involve
mitochondrial injury, oxidative stress, activation of c-Jun N-terminal kinase
(JNK) and release of danger-associated molecular patterns (DAMPs). DAMPs
stimulate innate immunity by binding pattern recognition receptors, such as Toll
like receptor 4 (TLR4) and the NOD-like receptor protein 3 (NLRP3) inflammasome,
which release a cascade of pro-inflammatory chemokines and cytokines. Thus,
lipotoxic hepatocellular injury attracts inflammatory cells, particularly
activated macrophages which surround ballooned hepatocytes as crown-like
structures. In both experimental and human NASH, livers contain cholesterol
crystals which are a second signal for NLRP3 activation; this causes interleukin
(IL)-1beta and IL18 secretion to attract and activate macrophages and
neutrophils. Injured hepatocytes also liberate plasma membrane-derived
extracellular vesicles; these have been shown to circulate in NASH and to be pro
inflammatory. The way metabolic dysfunction leads to lipotoxicity, innate immune
responses and the resultant pattern of cellular inflammation in the liver are
likely also relevant to hepatic fibrogenesis and hepatocarcinogenesis.
Pinpointing the key molecules involved pharmacologically should eventually lead
to effective pharmacotherapy against NASH.
PMID- 29956205
TI - Chemokines and Chemokine Receptors in the Development of NAFLD.
AB - Chemokines are chemo-attractants for leukocyte trafficking, growth, and
activation in injured and inflammatory tissues. The chemokine system is comprised
of 50 chemokine ligands and 20 cognate chemokine receptors. In the context of
liver diseases, leukocytes, hepatocytes, hepatic stellate cells, endothelial
cells, and vascular smooth muscle cells are capable of producing chemokines.
Chemokine receptors are typically expressed in various leukocyte subsets. Given
that inflammation is a critical factor for the transition from simple steatosis
to non-alcoholic steatohepatitis (NASH), and fibrosis, the chemokine system may
play a prominent role in the pathogenesis of non-alcoholic fatty liver disease
(NAFLD). Indeed, accumulating evidence shows elevated expression of chemokines
and their receptors in the livers of obese patients with advanced steatosis and
NASH. This chapter will discuss the underlying molecular mechanisms and the
therapeutic potential of the chemokine systems in the pathogenesis of NAFLD.
Among chemokines, we will highlight CCL2, CCL5, CXCL8-10, CX3CL1, and CXCL16 as
pivotal mediators in the development of steatosis, NASH, and fibrosis.
PMID- 29956206
TI - NAFLD Related-HCC: The Relationship with Metabolic Disorders.
AB - Obesity increases death rates of all cancers including non-alcoholic fatty liver
disease (NAFLD)-related hepatocellular carcinoma (NAFLD-HCC). NAFLD is considered
as hepatic manifestation of metabolic syndrome and is a multi-system disease.
Recent prevalence studies have intensively reported the association of obesity,
metabolic risk factors and HCC incidence and mortality. Mechanistic studies
suggested that immune response, PI3K/AKT/mTOR/PTEN pathway, mitochondrial
dysfunction and genetic alterations are important mediators in the progression of
NAFLD-HCC from metabolic disorder. In this book chapter, we attempt to collate
current research on NAFLD-HCC that lead to our understandings on how metabolic
disorders may intersect with cancer development. We also discussed the prevention
options of NAFLD-HCC in view of obesity and metabolic disorder. These studies
have extended our knowledge on the complicated mechanism of NAFLD and HCC, and
provided the prevention options of NAFLD-HCC in patients with obesity and
metabolic diseases.
PMID- 29956207
TI - Hepatocellular Carcinoma in Obesity: Finding a Needle in the Haystack?
AB - Obesity has been implicated in the development of hepatocellular carcinoma (HCC),
one of the most common malignancies worldwide with an increasing incidence in the
United States. Obesity and associated metabolic disorders such as type II
diabetes and the metabolic syndrome are key factors in the development of
nonalcoholic fatty liver disease (NAFLD) and promote several molecular mechanisms
that may contribute to hepatocarcinogenesis. The vast majority of HCC occur in
cirrhotic livers, but a subgroup of patients may develop HCC in non-advanced
NAFLD. While the incidence rate for noncirrhotic HCC is low, the population
attributable fraction is still significant due to the extraordinary prevalence of
obesity-associated liver disease. This is a challenge since HCC surveillance
cannot be provided to the large population of non-advanced NAFLD in a cost
efficient way and requires enhanced risk stratification strategies. Recent
advances may offer new clinical, laboratory, and genetic biomarkers and help us
meet this important public health need.
PMID- 29956208
TI - Dysregulated Epigenetic Modifications in the Pathogenesis of NAFLD-HCC.
AB - The pathogenesis of NAFLD is multi-faceted and mechanisms underlying the
progression from simple steatosis to NASH have not been fully deciphered. The
emerging field of epigenetics, an inheritable phenomenon capable of changing gene
expression without altering DNA sequence, unveils a new perspective on the
development of NAFLD and subsequent progression to HCC. In fact, numerous studies
have highlighted the potential involvement of unhealthy daily habits such as
physical inactivity and over-nutrition in the onset and development of NAFLD
through epigenetic mechanisms. This chapter will discuss several epigenetic
modulations including DNA methylation, histone modifications, functions of non
coding RNAs as well as RNA methylation implicated in the pathogenesis of NAFLD
HCC. On the basis of currently wealthy knowledge of DNA epigenetics, the rapidly
growing field of RNA epigenetics will certainly drive forward a new avenue of
research direction shedding light on the advancement of better diagnostics,
prognostics and therapeutics in the coming era of precision medicine.
PMID- 29956209
TI - The Influence of Gut Microbial Metabolism on the Development and Progression of
Non-alcoholic Fatty Liver Disease.
AB - Non-alcoholic fatty liver disease (NAFLD) is defined as the presence of excess
fat in the liver parenchyma in the absence of excess alcohol consumption and
overt inflammation. It has also been described as the hepatic manifestation of
metabolic syndrome (Than NN, Newsome PN, Atherosclerosis. 239:192-202, 2015). The
incidence of NAFLD has been reported to be 43-60% in diabetics, ~90% in patients
with hyperlipidemia and 91% in morbidly obese patients (Than NN, Newsome PN,
Atherosclerosis. 239:192-202, 2015, Machado M, Marques-Vidal P, Cortez-Pinto H, J
Hepatol, 45:600-606, 2006, Vernon G, Baranova A, Younossi ZM, Aliment Pharmacol
Ther, 34:274-285, 2011). The risk factors that have been associated with the
development of NAFLD include male gender, increasing age, obesity, insulin
resistance, diabetes and hyperlipidemia (Attar BM, Van Thiel DH, Sci World J,
2013:481893, 2013, Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E,
Gastaldelli A, Forum Nutr, 5:1544-1460, 2013). All of these risk factors have
been linked to alterations of the gut microbiota, ie., gut dysbiosis (He X, Ji G,
Jia W, Li H, Int J Mol Sci, 17:300, 2016). However, it must be pointed out that
the prevalence of NAFLD in normal weight individuals without metabolic risk
factors is ~16% (Than NN, Newsome PN, Atherosclerosis. 239:192-202, 2015). This
fact has led some investigators to hypothesize that the gut microbiota can impact
lipid metabolism in the liver independently of obesity-related metabolic factors
(Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold g, et al., Gut,
65:330 339, 2016) (Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua
C, et al., Gut, 62:1787-1794, 2013). In this chapter, we will explore the effect
of the gut microbiota on hepatic lipid metabolism and how this affects the
development of NAFLD.
PMID- 29956210
TI - Microbiota, Obesity and NAFLD.
AB - Non-alcoholic fatty liver disease (NAFLD) is an increasingly important cause of
chronic liver disease globally. Similar to metabolic syndrome and obesity, NAFLD
is associated with alternations in the gut microbiota and its related biological
pathways. While the exact pathophysiology of NAFLD remains largely unknown,
changes in intestinal inflammation, gut permeability, energy harvest, anaerobic
fermentation and insulin resistance have been described. In this chapter, we
review the relationship between the gut microbiota, obesity and NAFLD, and
highlight potential ways to modify the gut microbiota to help managing NAFLD
patients.
PMID- 29956211
TI - Autophagy, NAFLD and NAFLD-Related HCC.
AB - Non-alcoholic fatty liver disease (NAFLD) will become a dominant cause of
hepatocellular carcinoma (HCC) in the coming decade. Whereas the exact molecular
mechanisms underlying the progression from simple steatosis, through
steatohepatitis, to HCC remains largely unclear, emerging evidence has supported
a central role of defective autophagy in the pathogenesis of NAFLD and its
complications. Autophagy not only regulates lipid metabolism and insulin
resistance, but also protects hepatocytes from injury and cell death.
Nevertheless, in inflammation and tumorigenesis, the role of autophagy is more
paradoxical. In NAFLD, defective hepatic autophagy occurs at multiple levels
through numerous mechanisms and is causally linked to NAFLD-related HCC. In this
chapter, we summarize the regulation and function of autophagy in NAFLD and
highlight recent identification of potential pharmacological agents for restoring
autophagic flux in NAFLD.
PMID- 29956212
TI - Animal Models of Non-alcoholic Fatty Liver Diseases and Its Associated Liver
Cancer.
AB - Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases, which
include simple liver steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis
and hepatocellular carcinoma (HCC). It is a burgeoning health problem worldwide
in line with the trend towards unhealthy diet and increased prevalence of obesity
and type 2 diabetes mellitus (T2DM). Many animal models that illustrate both the
histology and pathology of human NAFLD have been established. It is important to
choose an animal model that best conforms to the aim of the study. This chapter
presents a critical analysis of the histopathology and pathogenesis of NAFLD and
the most commonly used and recently developed animal models of hepatic steatosis,
NASH and NAFLD-induced hepatocellular carcinoma (NAFLD-HCC). The main mechanisms
involved in the experimental pathogenesis of NAFLD in various animal models were
also discussed. This chapter also includes a brief summary of recent therapeutic
targets found using animal models. Although current animal models provide
important guidance in understanding the pathogenesis and development of NAFLD,
future study is essential to develop more precise models that better mimic the
disease spectrum for both improved mechanistic understanding and identification
of novel therapeutic options.
PMID- 29956213
TI - Current Prevention and Treatment Options for NAFLD.
AB - Non-alcoholic fatty liver disease (NAFLD) is now the most common chronic liver
disease worldwide and the second leading indication for liver transplantation and
the third leading cause of hepatocellular carcinoma (HCC) in the United States.
This chapter focuses on the prevention and management of NAFLD. Healthy lifestyle
is the cornerstone for the prevention and management of NAFLD and should be
recommended to every patient at risk or having established NAFLD. Despite the
high prevalence of NAFLD, it should be recognized that the majority of patients
will not develop liver-related complications; cardiovascular disease remains the
leading cause of death in NAFLD patients. Until further data are available,
pharmacological treatment should be restricted to selected patients with
confirmed non-alcoholic steatohepatitis. As some agents with primarily anti
fibrotic effect are currently being tested in NAFLD patients, significant
fibrosis and cirrhosis may become additional indications for treatment in the
future. Because of the surgical morbidity, currently bariatric surgery should
only be performed in patients with morbid obesity, although the long-term impact
of bariatric surgery on the histology of NAFLD is favorable.
PMID- 29956214
TI - Circulating insulin-like peptide 5 levels and its association with metabolic and
hormonal parameters in women with polycystic ovary syndrome.
AB - PURPOSE: Insulin-like peptide 5 (INSL5) is a gut peptide hormone that is a member
of relaxin/insulin superfamily. Growing evidence implicates the crucial role of
the peptide in some metabolisms including food intake, glucose homeostasis and
reproductive system. Polycystic ovary syndrome (PCOS) is involved in both
reproductive and metabolic issues. The aim of the study was determination of
circulating levels of INSL5 alteration in women with PCOS and evaluation of the
relationship between INSL5 and hormonal-metabolic parameters as well as carotid
intima media thickness (cIMT). METHODS: A total of 164 subjects were recruited in
this cross-sectional study (82 women with PCOS and 82 age- and BMI-matched
controls). Circulating INSL5 levels were assessed via ELISA method. High
resolution B-mode ultrasound was used to measure cIMT. The hormonal and metabolic
parameters of the recruited subjects were determined. RESULTS: Circulating INSL5
levels were significantly elevated in women with PCOS compared to controls (27.63
+/- 7.74 vs. 19.90 +/- 5.85 ng/ml, P < 0.001). The mean values of INSL5 were
significantly higher in overweight subjects compared to lean weight subjects in
both groups. The women with PCOS having insulin resistance have increased INSL5
compared to those of PCOS subjects without insulin resistance. INSL5 is
associated with insulin resistance, BMI, luteinizing hormone and free androgen
index. Multivariate logistic regression analyses revealed that the odds ratio for
having PCOS in the highest tertile of INSL5 was higher than in the lowest
tertile. CONCLUSIONS: PCOS subjects exhibited an elevation in circulating INSL5
levels along with a link between INSL5 level induction and metabolic-hormonal
parameters.
PMID- 29956215
TI - Pharmacokinetics of Tramadol and Celecoxib in Japanese and Caucasian Subjects
Following Administration of Co-Crystal of Tramadol-Celecoxib (CTC): A Randomised,
Open-Label Study.
AB - BACKGROUND AND OBJECTIVES: Co-Crystal of Tramadol-Celecoxib (CTC) is a first-in
class active pharmaceutical ingredient (API-API) co-crystal of rac-tramadol.HCl
and celecoxib in a 1:1 molecular ratio (100 mg CTC: 44 mg rac-tramadol.HCl and 56
mg celecoxib). Tramadol and celecoxib pharmacokinetics are modified after CTC
administration versus administration of reference products. This randomised, open
label, crossover, phase 1 study assessed CTC pharmacokinetics, dose
proportionality, safety and tolerability in Japanese and Caucasian subjects.
METHODS: CTC (100, 150 and 200 mg) was administered orally to healthy
Japanese/Caucasian subjects. Tramadol, O-desmethyltramadol and celecoxib plasma
concentrations were determined pre-dose and up to 48 h post-dose. Maximum
observed plasma concentration (Cmax), and area under the plasma concentration
time curve from dosing to last measurable concentration (AUCt) and from dosing
extrapolated to infinity (AUCinfinity) were evaluated. Dose proportionality was
assessed in a dose-adjusted bioavailability analysis of variance and in a power
model. Inter-cohort comparability of pharmacokinetic exposure was confirmed if
the ratio (Japanese cohort/Caucasian cohort) of geometric least-squares means and
corresponding 90% confidence intervals were 80-125%. Post hoc weight-adjusted
comparability analyses were performed. Safety was assessed throughout. RESULTS:
Sixty subjects (21 males/9 females per cohort) were randomised; 57 completed the
study. Cohorts were age and BMI matched; there were expected inter-cohort weight
differences. Exposure to each analyte increased in both cohorts with increasing
CTC dose. Tramadol's pharmacokinetic exposure was comparable between cohorts
after adjusting for body weight; the pharmacokinetic exposure of O
desmethyltramadol and celecoxib was increased in Japanese subjects. CONCLUSIONS:
Differences in pharmacokinetics were not sufficient to suggest that CTC dose
adjustment is required in Japanese subjects. CLINICAL TRIAL REGISTRATION:
EudraCT: 2015-003071-29.
PMID- 29956216
TI - Nonparametric dynamical model of cardiorespiratory responses at the onset and
offset of treadmill exercises.
AB - This paper applies a nonparametric modelling method with kernel-based
regularization to estimate the carbon dioxide production during jogging
exercises. The kernel selection and regularization strategies have been
discussed; several commonly used kernels are compared regarding the goodness-of
fit, sensitivity, and stability. Based on that, the most appropriate kernel is
then selected for the construction of the regularization term. Both the onset and
offset of the jogging exercises are investigated. We compare the identified
nonparametric models, which include both impulse response models and step
response models for the two periods, as well as the relationship between oxygen
consumption and carbon dioxide production. The result statistically indicates
that the steady-state gain of the carbon dioxide production in the onset of
exercise is bigger than that in the offset while the response time of both onset
and offset are similar. Compared with oxygen consumption, the response speed of
carbon dioxide production is slightly slower in both onset and offset period
while its steady-state gains are similar for both periods. The effectiveness of
the kernel-based method for the dynamic modelling of cardiorespiratory response
to exercise is also well demonstrated. Graphical Abstract Comparison between VO2
and VCO2 during onset and offset of exercise.
PMID- 29956217
TI - Gabapentin and Pregabalin and Risk of Atrial Fibrillation in the Elderly: A
Population-Based Cohort Study in an Electronic Prescription Database.
AB - INTRODUCTION: Gabapentin and pregabalin are widely prescribed to elderly people,
but data on their pharmacokinetics, safety, and efficacy in this population are
scarce. Neurological adverse effects are common. Atrial fibrillation (AF)
associated with their use has been described in several case reports and case
series, but the incidence is unknown. OBJECTIVE: The aim of this study was to
assess the association between exposure to gabapentin or pregabalin and AF in the
elderly. METHODS: Patients >= 65 years of age starting treatment with either
gabapentin or pregabalin between January 1 and March 31, 2015, free of
cardiovascular disease, and who did not receive the alternate study medications
were studied. They were compared with patients who initiated treatment with an
analgesic opiate or with alprazolam or diazepam. The two primary outcome
variables were a first claim of an oral anticoagulant plus an antiarrhythmic drug
(OAC + AA), or of an oral anticoagulant or an antiplatelet agent plus an
antiarrhythmic drug (OAC/APA + AA), in the 3 months after treatment initiation.
RESULTS: Compared with opiate analgesics, both gabapentin and pregabalin were
associated with an increased risk of initiating OAC/APA + AA. The incidence was 6
of 668 (9.0 per 1000 patients) with gabapentin, versus 12 of 3889 (3.1 per 1000)
with opiates, relative risk (RR) 2.91 (95% confidence interval [CI] 1.10-7.73),
and for pregabalin it was 6 of 698 (8.6 per 1000) RR 2.79 (95% CI 1.05-7.40). The
comparison with alprazolam/diazepam gave similar results. The risks did not vary
by age, sex, or co-treatment with NSAIDs, and they increased with dose.
CONCLUSION: In elderly patients free of cardiovascular disease, an association
between new exposure to gabapentin or pregabalin and initiating treatment for AF
was found. These results should be confirmed in other studies.
PMID- 29956218
TI - Role of Serotonin Transporter in Antidepressant-Induced Diabetes Mellitus: A
Pharmacoepidemiological-Pharmacodynamic Study in VigiBase(r).
AB - BACKGROUND: The association between antidepressant exposure and type 2 diabetes
mellitus is still debated. Moreover, the pharmacological mechanisms remain
unknown. OBJECTIVE: The objective of this study was to investigate this putative
relationship with the role of antidepressant pharmacological targets using the
'pharmacoepidemiological-pharmacodynamic' method. METHODS: First, we performed
case/non-case analyses in VigiBase(r) (the World Health Organization
international database of suspected adverse drug reactions) to examine a signal
of increased type 2 diabetes reporting (expressed as the reporting odds ratio and
its 95% confidence interval) for antidepressants in general; examine and rank
type 2 diabetes signals between the different pharmacological classes of
antidepressants and the different antidepressants (58 in total). Second, we
performed linear regression analyses to explore the association between the type
2 diabetes signal ranked between antidepressants and their binding affinities for
nine targets (serotonin, norepinephrine, dopamine transporters, 5-HT2C serotonin,
D2 dopamine, alpha1, alpha2 adrenergic, M3 muscarinic and H1 histamine
receptors). RESULTS: A significant type 2 diabetes signal was found for
antidepressants in general, three classes of antidepressants (tricyclic
antidepressants, serotonin reuptake inhibitors and "other" antidepressants) and
15 individual antidepressants in particular. Among the antidepressants, three
serotonin reuptake inhibitors [escitalopram (adjusted reporting odds ratio 1.15
[1.07-1.25]), paroxetine (1.15 [1.07-1.23]), sertraline (1.23 [1.17-1.31])] and
three "other" antidepressants [duloxetine (1.15 [1.07-1.23]), trazodone (1.20
[1.09-1.32]), venlafaxine (1.15 [1.08-1.23])] were the antidepressants most
frequently reported with type 2 diabetes. We found a significant correlation
between the type 2 diabetes signal and serotonin transporter affinity (slope =
0.14 [0.06-0.23], p = 0.003, R2 = 0.43) but not the other targets. CONCLUSION:
The present study suggests a potential role for serotonin transporter in
antidepressant-induced type 2 diabetes.
PMID- 29956219
TI - Authors' Response to Silverman and Colleagues' Comment on "Review of Case
Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid
Dependence".
PMID- 29956220
TI - Comment on "Review of Case Narratives from Fatal Overdoses Associated with
Injectable Naltrexone for Opioid Dependence".
PMID- 29956221
TI - Characterization and development of EST-SSR markers to study the genetic
diversity and populations analysis of Jerusalem artichoke (Helianthus tuberosus
L.).
AB - In recent years, Jerusalem artichoke has received widespread attention as a novel
source of sugar, biofuel, and animal feed. Currently, only few gDNA-SSRs derived
from sunflower were verified in the Jerusalem artichoke; therefore, it is
particularly important to develop SSR primer markers that belonged to Jerusalem
artichoke resources. Using EST data to develop EST-SSR markers is simple and
effective. In order to understand the general characteristics of SSR markers in
Jerusalem artichoke EST sequences and accelerate the use of SSR markers in
Jerusalem artichoke research. This study used 40,370 sequenced unigene fragments
and MISA software to identify SSR loci. The 48 pairs of EST-SSR primers assessed
for the identification of 45 varieties of Jerusalem artichoke. Cluster, genetic
diversity parameters and AMOVA analysis was conducted using the genetic
similarity coefficient, revealing genetic differences between 48 genetic
material. A total of 1204 SSR loci were identified with 13 different types of
repeats, distributed among 1020 EST sequences, of which trinucleotide repeats
were the most common, accounting for 38.21% of the total SSR loci. Among the 44
repeat motifs, AG/CT, AAG/CTT, and ATC/ATG motifs had the highest frequencies,
accounting for 22.45, 14.71, and 7.84% of all motifs, respectively. From these
sequences, 48 pairs of EST-SSR primers were designed, and 22 primer pairs for
loci with high polymorphism were selected to analyze the genetic diversity of 45
Jerusalem artichoke germplasm sources. The results indicated that the variation
range of the effective number of alleles for 22 primers ranged between 1.7502 and
4.5660. The Shannon's information index ranged between 0.6200 and 1.6423. The
variation range of PIC ranged between 0.3121 and 0.6662 with an average of
0.5184. Cluster analysis was conducted using the genetic similarity coefficient,
revealing significant genetic differences between Asian and European genetic
material. Cluster analysis revealed a relationship between the genotypes and
geographic origins of the Jerusalem artichoke. The results of AMOVA as well as
the genetic identity and genetic distance in the Jerusalem artichoke population
showed that there presented certain genetic heterogeneity in Jerusalem artichoke
genetic structure of 45 samples from seven different geographic populations. The
Jerusalem artichoke EST-SSR marker system established in this study provides an
effective molecular marker system for future research focused on Jerusalem
artichoke genetic diversity and the breeding of new varieties.
PMID- 29956222
TI - Association between STAT4 polymorphisms and risk of primary biliary cholangitis:
a meta-analysis.
AB - Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. Several
studies reported that SATA4 (signal transducer and activator of transcription 4)
polymorphisms were significantly associated with PBC susceptibility. In order to
derive a more comprehensive estimation of the association between STAT4 and PBC
risk, this meta-analysis was conducted. Thirteen eligible studies from 8 articles
with a total number of 11,310 cases and 27,844 controls were included in this
meta-analysis. Pooled odds ratios (OR) and 95% confidence intervals (CI) were
estimated with fixed effects model or random effects model. The results showed
statistically significant association between polymorphisms of rs7574865,
rs3024921, rs6752770, rs7601754 and rs10168266 in STAT4 and PBC risk under the
allelic effect model (rs7574865, T vs. G, OR = 1.24, 95% CI 1.14-1.35; rs3024921,
T vs. A, OR = 1.65, 95% CI 1.44-1.91; rs6752770, G vs. A, OR = 1.24, 95% CI 1.11
1.39; rs7601754, A vs. G, OR = 1.35, 95% CI 1.17-1.55; and rs10168266, T vs. C,
OR = 1.31, 95% CI 1.22-1.41). Furthermore, the rs7574865 polymorphism was
significantly associated with PBC risk under all genotype genetic models
(dominant effect model: TT + TG vs. GG, OR = 1.43, 95% CI 1.19-1.71; recessive
effect: TT vs. TG + GG, OR = 1.40, 95% CI 1.24-1.58; and co-dominant effect: TT
vs. GG, OR = 1.67, 95% CI 1.37-2.02). The sensitivity analysis by omitting one
study at a time showed that the results were stable. No publication bias was
indicated from both Begg's test and Egger's weighted regression. This meta
analysis suggested that polymorphisms of rs7574865, rs3024921, rs6752770,
rs7601754 and rs10168266 in STAT4 were significantly associated with the risk of
PBC.
PMID- 29956223
TI - High-Resolution Atomic Force Microscopy Imaging of Nucleic Acids.
AB - Exploring the limits of spatial resolution has been a constant in the history of
atomic force microscopy imaging. Since its invention in 1986, the AFM has beaten
the barrier of resolution continuously, thanks to technical developments,
miniaturization of tips, and implementation of new imaging modes. The double
helix structure of DNA has been always at the horizon of resolution. Today, this
milestone has been reached, not only imaging DNA but also its close relative
double-stranded RNA. Here, we provide a comprehensive description of the methods
employed and the steps required to image the helical periodicity of these two
nucleic acids with the sample immersed in a buffer solution.
PMID- 29956224
TI - Two Ligand Binding Sites in Serotonin Transporter Revealed by Nanopharmacological
Force Sensing.
AB - The number of ligand binding sites in neurotransmitter-sodium symporters has been
determined by crystal structure analysis and molecular pharmacology with
controversial results. Here, we designed molecular tools to measure the
interaction forces between the serotonin transporter (SERT) and S-citalopram on
the single-molecule level by means of atomic force microscopy. Force spectroscopy
allows for the extraction of dynamic information under physiological conditions
which is inaccessible via X-ray crystallography. Two populations of distinctly
different binding strength between S-citalopram and SERT were demonstrated in Na+
containing buffer. In Li+-containing buffer, SERT showed merely low-force
interactions, whereas the vestibular mutant SERT-G402H only displayed the high
force population. These observations provide physical evidence for the existence
of two different binding sites in SERT when tested under near-physiological
conditions.
PMID- 29956225
TI - AFM-Based Single-Molecule Force Spectroscopy of Proteins.
AB - Single-molecule force spectroscopy by AFM (AFM-SMFS) is an experimental
methodology that allows unequivocal sensitivity and control for investigating and
manipulating the mechanical properties of single molecules. The past 20 years of
AFM-SMFS has provided numerous breakthroughs in the understanding of the
mechanical properties and force-induced structural rearrangements of sugars, DNA,
and proteins. Here, we focus on the application of AFM-SMFS to study proteins,
since AFM-SMFS has succeeded in providing abundant information about protein
folding pathways, kinetics, interactions, and misfolding. In this chapter we
describe the experimental procedures for conducting a SMFS-AFM experiment
including purification of protein samples, setup and calibration of the AFM
instrumentation, and the thorough and unbiased analysis of resulting AFM data.
PMID- 29956226
TI - High-Resolution AFM-Based Force Spectroscopy.
AB - Atomic force microscopy (AFM)-based force spectroscopy is a powerful technique
which has seen significant enhancements in both force and time resolution in
recent years. This chapter details two AFM cantilever modification procedures
that yield high force precision over different temporal bandwidths. Specifically,
it explains a fairly straightforward method to achieve sub-pN force precision and
stability at low frequencies (<50 Hz) by removing the metal coatings from a
commercially available cantilever. A more involved procedure utilizing a focused
ion beam milling machine is required to maintain high force precision at enhanced
bandwidths. Both modification methods allow site-specific attachment of
biomolecules onto the apex area of the tips for force spectroscopy. The chapter
concludes with a comparative demonstration using the two cantilever modification
methods to study a lipid-protein interaction.
PMID- 29956227
TI - Polymer Nanoarray Approach for the Characterization of Biomolecular Interactions.
AB - Pair-wise interactions at the single-molecule level can be done with nanoprobing
techniques, such as AFM force spectroscopy, optical tweezers, and magnetic
tweezers. These techniques can be used to probe interactions between well
characterized assemblies of biomolecules, such as monomer-dimer, dimer-dimer, and
trimer-monomer. An important step of these techniques is the proper assembly of
dimers, trimers, and higher oligomers to enable the interactions to be probed. We
have developed a novel approach in which a defined number of peptides are
assembled along a flexible polymeric molecule that serves as a linear matrix,
termed as flexible nanoarray (FNA). The construct is synthesized with the use of
phosphoramidite chemistry (PA), in which non-nucleoside PA spacers and standard
oligonucleotide synthesis are used to grow the polymeric chain with the desired
length. The reactive sites are incorporated during FNA synthesis. As a result,
the FNA polymer contains a set of predesigned reactive sites to which the
peptides are covalently conjugated. We describe the protocol for the synthesis of
FNA and the application of this methodology to measure the molecular interactions
between amyloid peptides of monomer-monomer, monomer-dimer, and dimer-dimer.
PMID- 29956228
TI - Measuring Single-Molecule Twist and Torque in Multiplexed Magnetic Tweezers.
AB - Magnetic tweezers permit application of precisely calibrated stretching forces to
nucleic acid molecules tethered between a surface and superparamagnetic beads. In
addition, magnetic tweezers can control the tethers' twist. Here, we focus on
recent extensions of the technique that expand the capabilities of conventional
magnetic tweezers by enabling direct measurements of single-molecule torque and
twist. Magnetic torque tweezers (MTT) still control the DNA or RNA tether's
twist, but directly measure molecular torque by monitoring changes in the
equilibrium rotation angle upon overwinding and underwinding of the tether. In
freely orbiting magnetic tweezers (FOMT), one end of the tether is allowed to
rotate freely, while still applying stretching forces and monitoring rotation
angle. Both MTT and FOMT have provided unique insights into the mechanical
properties, structural transitions, and interactions of DNA and RNA. Here, we
provide step-by-step protocols to carry out FOMT and MTT measurements. In
particular, we focus on multiplexed measurements, i.e., measurements that record
data for multiple nucleic acid tethers at the same time, to improve statistics
and to facilitate the observation of rare events.
PMID- 29956229
TI - AFM-Based Characterization of Electrical Properties of Materials.
AB - Capabilities of atomic force microscopy (AFM) for characterization of local
electrical properties of materials are presented in this chapter. At the
beginning the probe-sample force interactions, which are employed for detection
of surface topography and materials properties, are described theoretically in
their application in different AFM modes and electrical techniques. The
electrical techniques, which are based on detection of electrostatic probe-sample
forces, are outlined in AFM contact and oscillatory resonant modes. The basic
features of the detection of surface potential and capacitance gradients are
explained. The applications of these techniques are illustrated on metals,
surfactant compounds, semiconductors, and different polymers. Practical
recommendations on use of the AFM-based electrical methods and the related
challenges are given in the last section.
PMID- 29956230
TI - Supported Lipid Bilayers for Atomic Force Microscopy Studies.
AB - Nanoimaging methods, atomic force microscopy (AFM) in particular, are widely used
to study the interaction of biological molecules with the supported lipid bilayer
(SLB), which itself is a traditional model for cellular membranes. Success in
these studies is based on the availability of a stable SLB for the required
observation period, which can extend several hours. The application of AFM
requires that the SLB have a smooth morphology, thus enabling visualization of
proteins and other molecules on its surface. Herein, we describe protocols for
SLB assembly by using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and
1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS) on a mica support. Our
methodology enables us to assemble defect-free POPC and POPS SLBs that remain
stable for at least 8 h. The application of such smooth and stable surfaces is
illustrated by monitoring of the on-surface aggregation of amyloid proteins with
the use of time-lapse AFM.
PMID- 29956231
TI - Quantifying Small Molecule Binding Interactions with DNA Nanostructures.
AB - DNA nanostructures and hybrid DNA-protein materials are attractive solutions to
many applications in biotechnology and material science because of their
controllable molecule-level features. Critical to a complete description and
characterization of these technologies is the quantification of binding affinity
between DNA nanostructures and small molecules relevant to the application at
hand. This protocols chapter described a series of experimental and in silico
analyses that can be used to described and quantify ligand binding interactions
between DNA nanostructures (DNA DX tiles), short double stranded DNA fragments,
and arbitrary small molecules. The described methods include microscale
thermophoresis, ligand completion assays, circular dichroism spectroscopy, and
AutoDock simulations. The protocols use organophosphates and model chemical nerve
agents as examples, but the methods described here are broadly applicable.
PMID- 29956232
TI - Optimum Substrates for Imaging Biological Molecules with High-Speed Atomic Force
Microscopy.
AB - Recent progresses in high-speed atomic force microscopy (HS-AFM) have enabled us
to directly visualize dynamic processes of various proteins in liquid conditions.
One of the key factors leading to successful HS-AFM observations is the selection
of an appropriate substrate depending on molecules to be observed. For the HS-AFM
imaging, a target molecule must be absorbed on a substrate by controlling its
orientation without impairing the dynamics or physiological function of the
molecule. In this chapter, we describe protocols for preparation of substrates
that have been used for HS-AFM and then introduce observation examples on dynamic
processes of biological molecules.
PMID- 29956233
TI - High-Resolution and High-Speed Atomic Force Microscope Imaging.
AB - The advent of high-speed atomic force microscopy (HS-AFM) over the recent years
has opened up new horizons for the study of structure, function and dynamics of
biological molecules. HS-AFM is capable of 1000 times faster imaging than
conventional AFM. This circumstance uniquely enables the observation of the
dynamics of all the molecules present in the imaging area. Over the last 10
years, the HS-AFM has gone from a prototype-state technology that only a few labs
in the world had access to (including ours) to an established commercialized
technology that is present in tens of labs around the world. In this protocol
chapter we share with the readers our practical know-how on high resolution HS
AFM imaging.
PMID- 29956234
TI - High-Speed Atomic Force Microscopy of Individual Amyloidogenic Protein
Assemblies.
AB - High-speed atomic force microscopy (HS-AFM) with high spatiotemporal resolution
allows for the video imaging of the conformational changes of individual
molecules in an observation area in liquid at nanometer-scale spatial resolution.
This method verifies the molecular mechanism and reveals the structural dynamics
of relevant biomolecules for various biological phenomena. Here, we describe the
methods for HS-AFM observation and the analysis of the structural dynamics of
individual amyloidogenic protein assemblies using amyloid beta 1-42 as an
example.
PMID- 29956235
TI - Direct Observation of Dynamic Movement of DNA Molecules in DNA Origami Imaged
Using High-Speed AFM.
AB - The visualization of biomolecules is a straightforward way to elucidate the
physical properties of molecules and their reaction processes. Atomic force
microscopy (AFM) enables the direct imaging of biomolecules under physiological
conditions at nanometer-scale spatial resolution. Because AFM visualizes all
molecules in a scanning area, an observation scaffold is required for the target
specific imaging of molecules in the dynamic state. The DNA origami technology
allows the precise placement of target molecules in a designed nanostructure, and
the detection of the molecules at the single-molecule level. DNA origami is
applied for visualizing the detailed motions of molecules using high-speed AFM
(HS-AFM), which enables the analysis of the dynamic movement of biomolecules in a
subsecond time resolution. Here, we describe the combination of the DNA origami
system with HS-AFM for the imaging of DNA structural changes controlled by
photoresponsive molecules. The hybridization and dehybridization of
photoresponsive oligonucleotides were visualized directly using this observation
system. These target-oriented observation systems should contribute to the
detailed analysis of biomolecules in real time with molecular resolution.
PMID- 29956236
TI - Assembly of Centromere Chromatin for Characterization by High-Speed Time-Lapse
Atomic Force Microscopy.
AB - Atomic force microscopy (AFM) is an imaging technique that enables single
molecule characterization of biological systems at nanometer resolution. Imaging
in ambient conditions can provide details of the conformational states and
interactions of a population of molecules which is well complemented by single
molecule imaging of the systems dynamics using time-lapse AFM imaging, in which
images are capture at rates of 10-15 frames per second in an aqueous buffer. Here
we describe the assembly and preparation of nucleosomes containing centromere
protein A (CENP-A) for AFM imaging in both static and time-lapse modes. The AFM
imaging and data analysis techniques described enable characterization of the
extent of DNA wrapping around the histone core and time-resolved visualization of
the systems intrinsic dynamic behaviors.
PMID- 29956237
TI - High-Speed Force Spectroscopy for Single Protein Unfolding.
AB - Single-molecule force spectroscopy (SMFS) measurements allow for quantification
of the molecular forces required to unfold individual protein domains. Atomic
force microscopy (AFM) is one of the long-established techniques for force
spectroscopy (FS). Although FS at conventional AFM pulling rates provides
valuable information on protein unfolding, in order to get a more complete
picture of the mechanism, explore new regimes, and combine and compare
experiments with simulations, we need higher pulling rates and MUs-time
resolution, now accessible via high-speed force spectroscopy (HS-FS). In this
chapter, we provide a step-by-step protocol of HS-FS including sample
preparation, measurements and analysis of the acquired data using HS-AFM with an
illustrative example on unfolding of a well-studied concatamer made of eight
repeats of the titin I91 domain.
PMID- 29956238
TI - Probing RNA-Protein Interactions with Single-Molecule Pull-Down Assays.
AB - Recent advances in single-molecule techniques allow for dynamic observations of
the interactions between various protein assemblies and RNA molecules with high
spatiotemporal resolution. However, it remains challenging to obtain functional
eukaryotic protein complexes and cost-effective fluorescently labeled RNAs to
study their interactions at the single-molecule level. Here, we describe
protocols combining single-molecule fluorescence with various protein complex
pull-down techniques to determine the function of RNA-interacting protein
complexes of interest. We provide step-by-step guidance for using novel single
molecule techniques including RNA labeling, protein complexes purification, and
single-molecule imaging. As a proof-of-concept of the utility of our single
molecule approaches, we show how human Dicer and its cofactor TRBP orchestrate
the biogenesis of microRNA in real time. These single-molecule pull-down and
fluorescence assays provide sub-second time resolution and can be applied to
various ribonucleoprotein complexes that are essential for cellular processes.
PMID- 29956239
TI - Preparing Frozen-Hydrated Protein-Nucleic Acid Assemblies for High-Resolution
Cryo-EM Imaging.
AB - High-resolution image acquisition and structure determination by cryo-electron
microscopy is becoming increasingly streamlined. Preparing electron-microscopy
grids of suitable quality remains, however, a critical bottleneck. Strategies to
achieve particle monodispersity, optimal sample concentration and suitable ice
thickness can vary from specimen to specimen. In this book chapter we describe
our protocols for negative-stain grid and cryo-grid preparation, which we apply
to studying protein-nucleic acid complexes.
PMID- 29956240
TI - Probing Chromatin Structure with Magnetic Tweezers.
AB - Magnetic tweezers form a unique tool to study the topology and mechanical
properties of chromatin fibers. Chromatin is a complex of DNA and proteins that
folds the DNA in such a way that meter-long stretches of DNA fit into the micron
sized cell nucleus. Moreover, it regulates accessibility of the genome to the
cellular replication, transcription, and repair machinery. However, the structure
and mechanisms that govern chromatin folding remain poorly understood, despite
recent spectacular improvements in high-resolution imaging techniques. Single
molecule force spectroscopy techniques can directly measure both the extension of
individual chromatin fragments with nanometer accuracy and the forces involved in
the (un)folding of single chromatin fibers. Here, we report detailed methods that
allow one to successfully prepare in vitro reconstituted chromatin fibers for use
in magnetic tweezers-based force spectroscopy. The higher-order structure of
different chromatin fibers can be inferred from fitting a statistical mechanics
model to the force-extension data. These methods for quantifying chromatin
folding can be extended to study many other processes involving chromatin, such
as the epigenetic regulation of transcription.
PMID- 29956241
TI - Single-Molecule and Ensemble Methods to Probe Initial Stages of RNP Granule
Assembly.
AB - Ribonucleoprotein (RNP) granules are membraneless organelles, consisting of high
local concentrations of RNA and proteins bearing intrinsically disordered regions
(IDRs). They are formed by liquid-liquid phase separation (LLPS). In
neurodegenerative diseases such as ALS, mutations in granule proteins such as FUS
and TDP-43 accelerate abnormal liquid to solid transition of RNP granules,
leading to formation of fiber-like structures. Methods to study granules must be
carefully selected based on the stage of granule's life. Here we describe a
strategic combination of single-molecule biophysical and ensemble biochemical
techniques that may be employed to extract insightful information about early
stages of RNP granule formation. Protein-RNA interaction and stoichiometry of the
complex in the early soluble stage of RNP assembly can be probed by single
molecule FRET (smFRET) assay and electrophoretic mobility shift assay (EMSA),
respectively. RNP-RNP interaction that likely contributes to RNP nucleation can
be reported on by a smFRET-based RNA annealing assay. The next stage in the
assembly pathway, that is, phase separation from diffused to liquid-like
droplets, may be monitored by a phase separation assay. Finally, RNP granules
isolated from mammalian cells can be investigated using a unique single-molecule
pull-down (SiMPull) assay.
PMID- 29956242
TI - Correlative Atomic Force and Single-Molecule Fluorescence Microscopy of
Nucleoprotein Complexes.
AB - Correlative imaging by fluorescence and atomic force microscopy provides a
versatile tool to extract orthogonal information on structurally heterogeneous
biomolecular assemblies. In this chapter, we describe an integrated setup for
correlative fluorescence and force microscopy. We present factors influencing
data quality, as well as step-by-step protocols for sample preparation, data
acquisition, and data processing that yield nanoscale topographic resolution,
high image registration accuracy, and single-fluorophore sensitivity. We
demonstrate the capabilities of the approach through simultaneous
characterization of mesoscale geometry and composition in a multipart
nucleoprotein complex.
PMID- 29956243
TI - Sensing the Ultrastructure of Bacterial Surfaces and Their Molecular Binding
Forces Using AFM.
AB - In this protocol, we provide a detailed step-by-step bacterial surface imaging
and molecular analysis procedure. With SPM (scanning probe microscopy)-based
dynamic force microscopy (DFM) imaging, we achieved a so far unprecedented
resolution of ~1 nm on the outer surface layer of Tannerella forsythia and
monitored the production of curli fibers on Escherichia coli in physiological
conditions. Moreover, using these immobilization methods, single-molecule force
spectroscopy experiments were conducted on living bacterial cells.
PMID- 29956244
TI - Nanoscale Visualization of Bacterial Microcompartments Using Atomic Force
Microscopy.
AB - Bacterial microcompartments (BMCs) are polyhedral protein organelles in many
prokaryotes, playing significant roles in metabolic enhancement. Due to their
self-assembly and modularity nature, BMCs have gained increased interest in
recent years, with the intent of constructing new nanobioreactors and scaffolding
to promote cellular metabolisms and molecule delivery. In this chapter, we
describe the technique of atomic force microscopy (AFM) as a method to study the
self-assembly dynamics and physical properties of BMCs. We focus on the sample
preparation, the measurement procedure, and the data analysis for high-speed AFM
imaging and nanoindentation-based spectroscopy, which were used to determine the
assembly dynamics of BMC shell proteins and the nanomechanics of intact BMC
structures, respectively. The described methods could be applied to the study of
other types of self-assembling biological organelles.
PMID- 29956245
TI - Time-Resolved Imaging of Bacterial Surfaces Using Atomic Force Microscopy.
AB - Time-resolved atomic force microscopy (AFM) offers countless new modes by which
to study bacterial cell physiology on relevant time scales, from mere
milliseconds to hours and days on end. In addition, time-lapse AFM acts as a
complementary tool to optical fluorescence microscopy (OFM), for which the
combination offers a correlative link between the physical manifestation of
bacterial phenotypes and molecular mechanisms obeying those principles. Herein we
describe the essential materials and methods necessary for conducting time
resolved AFM and dual AFM/OFM experiments on bacteria.
PMID- 29956246
TI - Probing Bacterial Adhesion at the Single-Molecule and Single-Cell Levels by AFM
Based Force Spectroscopy.
AB - Functionalization of AFM probes with biomolecules or microorganisms allows for a
better understanding of the interaction mechanisms driving microbial adhesion.
Here we describe the most commonly used protocols to graft molecules and bacteria
to AFM cantilevers. The bioprobes obtained that way enable to measure forces down
to the single-cell and single-molecule levels.
PMID- 29956247
TI - Fluorescence Correlation Spectroscopy on Genomic DNA in Living Cells.
AB - Fluorescence correlation spectroscopy (FCS) is a powerful technique used to
measure diffusion, fluctuations, and other transport processes in biomolecular
systems. It is, however, prone to artifacts and subject to considerable
experimental difficulties when applied to living cells. In this chapter, we
provide protocols to conduct quantitative FCS measurements on DNA inside living
eukaryotic and prokaryotic cells. We discuss sample preparation, dye selection
and characterization, FCS data acquisition, and data analysis, including a method
to com pensate for photobleaching to obtain quantitatively meaningful spectra.
PMID- 29956248
TI - Three-Dimensional Tracking of Quantum Dot-Conjugated Molecules in Living Cells.
AB - Here, we describe protocols for three-dimensional tracking of single quantum dot
conjugated molecules with nanometer accuracy in living cells using conventional
fluorescence microscopy. The technique exploits out-of-focus images of single
emitters combined with an automated pattern-recognition open-source software that
fits the images with proper model functions to extract the emitter coordinates.
We describe protocols for targeting quantum dots to both membrane components and
cytosolic proteins.
PMID- 29956249
TI - AFM Indentation Analysis of Cells to Study Cell Mechanics and Pericellular Coat.
AB - Atomic force microscopy (AFM) indentation analysis of cells is a unique method of
measuring stiffness of the cell body and physical properties of its pericellular
coat. These cell parameters correlate with cells of abnormality and diseases.
Viable biological cells can be studied with this method directly in a culture
dish with no special preparation. Here we describe a step-by-step method to
analyze the AFM force-indentation curves to derive cell mechanics (the modulus of
elasticity of the cell body) and the parameters of the pericellular coat (density
and the thickness of the coat layer). Technical details, potential difficulties,
and points of special attention are described.
PMID- 29956250
TI - Imaging of Soft and Biological Samples Using AFM Ringing Mode.
AB - Ringing mode of atomic force microscopy (AFM) enables imaging the surfaces of
biological samples, cells, tissue, biopolymers, etc. to obtain unique
information, such as the size of molecules pulled by the AFM probe from the
sample surface, heights of the sample at different load forces, etc. (up to eight
different imaging channels can be recorded simultaneously, which is in addition
to five channels already available in other rival modes). The imaging can be done
in both air (gases) and liquid (buffers). In addition, the images obtained in
ringing mode do not have several common artifacts and can be collected up to 20*
faster compared to the rival imaging modes. Here we describe a step-by-step
approach to collect images in ringing mode applied to biological and soft
materials in general. Technical details, potential difficulties, and points of
special attention are described.
PMID- 29956251
TI - Probing Single Virus Binding Sites on Living Mammalian Cells Using AFM.
AB - In the last years, atomic force microscopy (AFM)-based approaches have evolved
into a powerful multiparametric tool that allows biological samples ranging from
single receptors to membranes and tissues to be probed. Force-distance curve
based AFM (FD-based AFM) nowadays enables to image living cells at high
resolution and simultaneously localize and characterize specific ligand-receptor
binding events. In this chapter, we present how FD-based AFM permits to
investigate virus binding to living mammalian cells and quantify the kinetic and
thermodynamic parameters that describe the free-energy landscape of the single
virus-receptor-mediated binding. Using a model virus, we probed the specific
interaction with cells expressing its cognate receptor and measured the affinity
of the interaction. Furthermore, we observed that the virus rapidly established
specific multivalent interactions and found that each bond formed in sequence
strengthens the attachment of the virus to the cell.
PMID- 29956253
TI - Methods for Atomic Force Microscopy of Biological and Living Specimens.
AB - Two main precautions must be taken into account to obtain high-resolution
morphological and nanomechanical characterization of biological specimens with an
atomic force microscope: the tip-sample interaction and the sample-substrate
adhesion. In this chapter we discuss the necessary steps for a correct
preparation of three types of biological samples: erythrocytes, bacteria, and
osteoblasts. The main goal is to deliver reproducible protocols to produce good
cellular adhesion and minimizing the morphological alterations of the specimens.
PMID- 29956252
TI - Applications of Atomic Force Microscopy for Adhesion Force Measurements in
Mechanotransduction.
AB - Adhesive interactions between living cells or ligand-receptor interactions can be
studied at the molecular level using atomic force microscopy (AFM). Adhesion
force measurements are performed with functionalized AFM probes. In order to
measure single ligand-receptor interactions, a cantilever with a pyramidal tip is
functionalized with a bio-recognized ligand (e.g., extracellular matrix protein).
The ligand-functionalized probe is then brought into contact with a cell in
culture to investigate adhesion between the respective probe-bound ligand and
endogenously expressed cell surface receptors (e.g., integrins or other adhesion
receptor). For experiments designed to examine cell-cell adhesions, a single cell
is attached to a tipless cantilever which is then brought into contact with other
cultured cells. Force curves are recorded to determine the forces necessary to
rupture discrete adhesions between the probe-bound ligand and receptor, or to
determine total adhesion force at cell-cell contacts. Here, we describe the
procedures for measuring adhesions between (a) fibronectin and alpha5beta1
integrin, and (b) breast cancer cells and bone marrow endothelial cells.
PMID- 29956254
TI - Single Molecule Imaging in Live Embryos Using Lattice Light-Sheet Microscopy.
AB - In the past decade, live-cell single molecule imaging studies have provided
unique insights on how DNA-binding molecules such as transcription factors
explore the nuclear environment to search for and bind to their targets. However,
due to technological limitations, single molecule experiments in living specimens
have largely been limited to monolayer cell cultures. Lattice light-sheet
microscopy overcomes these limitations and has now enabled single molecule
imaging within thicker specimens such as embryos. Here we describe a general
procedure to perform single molecule imaging in living Drosophila melanogaster
embryos using lattice light-sheet microscopy. This protocol allows direct
observation of both transcription factor diffusion and binding dynamics. Finally,
we illustrate how this Drosophila protocol can be extended to other thick samples
using single molecule imaging in live mouse embryos as an example.
PMID- 29956255
TI - Silver Filler Pre-embedding to Enhance Resolution and Contrast in
Multidimensional SEM: A Nanoscale Imaging Study on Liver Tissue.
AB - Contemporarily, serial block-face scanning electron microscopy (SBF-SEM) has
emerged as an immensely powerful nanoscopic imaging technique, capable of
generating large-volume three-dimensional information on a variety of biological
specimens in a semiautomated manner. Despite the plethora of insights and
advantages provided by SBF-SEM, a major challenge inherent to the technique is
that of electron charging, which ultimately reduces attainable resolution and
detracts from overall image quality. In this chapter, we describe a pre-embedding
approach that involves infiltration of tissue with a highly conductive silver
filler suspension following primary fixation. Such an approach is demonstrated to
improve overall sample conductivity, resulting in the minimization of charging
under high-vacuum conditions and an improvement in lateral resolution and image
contrast. The strength of this sample preparation approach for SBF-SEM is
illustrated on liver tissue.
PMID- 29956256
TI - Nanoscale Dynamics and Energetics of Proteins and Protein-Nucleic Acid Complexes
in Classical Molecular Dynamics Simulations.
AB - The present article describes techniques for classical simulations of proteins
and protein-nucleic acid complexes, revealing their dynamics and protein
substrate binding energies. The approach is based on classical atomistic
molecular dynamics (MD) simulations of the experimentally determined structures
of the complexes. MD simulations can provide dynamics of complexes in realistic
solvents on microsecond timescales, and the free energy methods are able to
provide Gibbs free energies of binding of substrates, such as nucleic acids, to
proteins. The chapter describes methodologies for the preparation of computer
models of biomolecular complexes and free energy perturbation methodology for
evaluating Gibbs free energies of binding. The applications are illustrated with
examples of snapshots of proteins and their complexes with nucleic acids, as well
as the precise Gibbs free energies of binding.
PMID- 29956257
TI - Pollution levels and risk assessment of perfluoroalkyl acids (PFAAs) in beef
muscle and liver from southern Xinjiang.
AB - The presence of perfluoroalkyl acids (PFAAs) in animal foods is worldwide, and
their fate and spatial distribution in Xinjiang are not well understood. In this
study, beef muscle and liver collected from five major cities in southern
Xinjiang were analyzed (n = 70) for 13 PFAAs using an ion-pairing method combined
with HPLC-MS/MS. Overall, PFAA contamination was widespread, exceeding 50% of
samples with concentrations ranged from below the limits of detection to 6.118
ng/g. Perfluorooctane sulfonate, perfluorooctanoic acid, and perfluoroundecanoic
acid were the predominant PFAAs of ten detected compounds, with maximum
concentrations in Korla liver samples of 2.543, 0.856, and 1.386 ng/g,
respectively. When comparing the five cities, the highest levels and detection
frequencies were observed in samples from Korla (muscle, 0.013 ng/g; liver, 3.336
ng/g), followed by Yanqi, Akesu, Kashgar, and Hotan. The different pollution
patterns and distribution profiles of PFAAs among cities were significantly
related to local economy and geographical conditions. In addition, the dietary
intake assessments for PFAAs showed that samples originating from Korla had the
greatest impact on human health, but the total hazard ratio was 0.814 * 10-3,
which is far less than 1, indicating that consumption of beef muscle and liver
poses no immediate harm to local residents.
PMID- 29956258
TI - Surface modification of sludge-derived carbon by phosphoric acid as new
electrocatalyst for degradation of acetophenone.
AB - Sludge-derived carbons (SCs) were modified by different acids and used as
electrocatalyst for electrochemical oxidation degradation of acetophenone. The
results showed that SC treated with phosphoric acid (H3PO4-SC) exhibited the
highest catalytic activity. The degradation efficiency of acetophenone reached
87.0%, and TOC removal was 72.3% under the conditions of 100 mg L-1 acetophenone,
90 mA cm-2, and 180 min reaction time. The element content and chemical state of
H3PO4-SC were measured by XRF, XRD, TGA, FTIR, and Mossbauer spectra, and the
results indicated that ferric iron and phosphate on the surface of H3PO4-SC might
play the main role in acetophenone degradation. The carbonyl-13C-labeled
acetophenone was first used to investigate the degradation of acetophenone in
electrochemical oxidation by NMR.
PMID- 29956259
TI - Di-metal-doped sulfur resisting perovskite catalysts for highly efficient H2-SCR
of NO.
AB - Lanthanide perovskite catalysts doped with limited palladium (to improve
activity) and cerium (to improve sulfur resistance) were prepared using sol-gel
method. In different B sites, lanthanide perovskites were studied at harsh
conditions for H2 selective catalytic reduction of NO. The activity sequence was
as follows: LaCeMnPd > LaCeCoPd > LaCeFePd. LaCeMnPd had a high NO conversion of
96.6% at only 150 degrees C. And it also had a surprising SO2 resistance in
different SO2 concentrations. After cutting out SO2, NO conversion recovered
rapidly to its original level, indicating that the slight deactivation was
reversible. In addition, the effect of gas hourly space velocity, H2/NO ratio,
O2, and SO2 concentration was studied. And XRD, energy-dispersive X-ray, SEM,
XPS, H2-temperature programmed reduction, and NH3-temperature programmed
desorption were performed to characterize the catalysts. Graphical abstract ?.
PMID- 29956260
TI - Utilization of rice husk to enhance calcium oxide-based sorbent prepared from
waste cockle shells for cyclic CO2 capture in high-temperature condition.
AB - The CO2 capture capacity and cyclic stability of calcium oxide (CaO) prepared
from cockle shells (CS) were enhanced by incorporating rice husk (RH) and binder
through wet-mixing method. The cyclic reaction of calcination and carbonation was
demonstrated using thermal gravimetric analyzer (TGA) which the calcination was
performed in a pure N2 environment at 850 degrees C for 20 min and carbonation
at 650 degrees C for 30 min in 20 vol% of CO2 in N2. The analysis using x-ray
fluorescence (XRF) identified silica (Si) as the major elements in the sorbents.
The RH-added sorbents also contained several types of metal elements such as
which was a key factor to minimize the sintering of the sorbent during the cyclic
reaction and contributed to higher CO2 capture capacity. The presence of various
morphologies also associated with the improvement of the synthesized sorbents
performance. The highest initial CO2 capture capacity was exhibited by CS+10%RH
sorbent, which was 12% higher than the RH-free sorbent (CS). However, sorbents
with the higher RH loading amount such as 40 and 50 wt% were preferred to
maintain high capture capacity when the sorbents were regenerated and extended to
the cyclic reaction. The sorbents also demonstrated the lowest average sorption
decay, which suggested the most stable sorbent for cyclic-reaction. Once
regenerated, the capture capacity of the RH-added sorbent was further increased
by 12% when clay was added into the sorbent. Overall, the metal elements in RH
and clay were possibly the key factor that enhances the performance of CaO
prepared from CS, particularly for cyclic CO2 capture. Graphical abstract Cyclic
calcination and carbonation reaction.
PMID- 29956261
TI - The influence of solid-liquid coefficient in the fate of pharmaceuticals and
personal care products in aerobic wastewater treatment.
AB - Wastewater treatment plants (WWTPs) are considered to be a source of
environmental contamination by micropollutants, especially from pharmaceuticals
and personal care products (PCPs). The pathway of those compounds during sewage
treatment has been investigated, but data from real-scale WWTPs is still missing
(for example, the values of the solid-liquid coefficient (Kd) during treatment).
This paper uses the Kd values for some pharmaceuticals and PCPs (fenofibrate,
gemfibrozil, propranolol, metoprolol, salicylic acid, acetylsalicylic acid,
ibuprofen, diclofenac, naproxen, fenoprofen, caffeine, triclosan, methylparaben,
ethylparaben, propylparaben, butylparaben, and benzylparaben) to describe the
micropollutants' behavior in the treatment process. In order to attain this data,
an aerobic wastewater treatment plant located in Brazil was studied. Six
samplings were carried out and a mass balance was performed, associating the
concentrations of the micropollutants in the liquid phase with the solid phase
(sludge and suspended solids). Of all the compounds analyzed, caffeine was the
most biodegradable pollutant, as almost 98% of its mass was biodegraded. In
contrast, triclosan had the highest load in sludge (median of 163.0 mg day-1) and
adsorbed in SS (median of 0.593 mg day-1) at the output. Summing up, each
micropollutant had a specific way to be removed during wastewater treatment.
PMID- 29956263
TI - Monitoring Progressive Multiple Sclerosis with Novel Imaging Techniques.
AB - Imaging markers for monitoring disease progression in progressive multiple
sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease
evolution and to test effective treatments in clinical trials. Advanced imaging
techniques that have the advantage of metrics with increased sensitivity to short
term tissue changes and increased specificity to the structural abnormalities
characteristic of PMS have recently been applied in clinical trials of PMS. In
this review, we (1) provide an overview of the pathological features of PMS, (2)
summarize the findings of research and clinical trials conducted in PMS which
have applied conventional and advanced magnetic resonance imaging techniques and
(3) discuss recent advancements and future perspectives in monitoring PMS with
imaging techniques.
PMID- 29956264
TI - The roles of order, distance, and interstitial items in temporal visual
statistical learning.
AB - Humans are adept at learning regularities in a visual environment, even without
explicit cues to structure and in the absence of instruction-this has been termed
"visual statistical learning" (VSL). The nature of the representations resulting
from VSL are still poorly understood. In five experiments, we examined the
specificity of temporal VSL representations. In Experiments 1A, 1B, and 2, we
compared recognition rates of triplets and all embedded pairs to chance. Robust
learning of all structures was evident, and even pairs of non-adjacent items in a
sequentially presented triplet (AC extracted from a triplet composed of ABC) were
recognized at above-chance levels. In Experiment 3, we asked whether people could
recognize rearranged pairs to examine the flexibility of learned representations.
Recognition of all possible orders of target triplets and pairs was significantly
higher than chance, and there were no differences between canonical orderings and
their corresponding randomized orderings, suggesting that learners were not
dependent upon originally experienced stimulus orderings to recognize co
occurrence. Experiment 4 demonstrates the essential role of an interstitial item
in VSL representations. By comparing the learning of quadruplet sets (e.g., ABCD)
and triplet sets (e.g., ABC), we found learning of AC and BD in ABCD (quadruplet)
sets were better than the learning of AC in ABC (triplet) sets. This pattern of
results might result from the critical role of interstitial items in statistical
learning. In short, our work supports the idea of generalized representation in
VSL and provides evidence about how this representation is structured.
PMID- 29956265
TI - A Brief Overview of Progranulin in Health and Disease.
AB - The purpose of this brief overview of the progranulin protein is to provide a
sense of the range and extent of the roles of progranulin in normal physiology
and pathology. Progranulin has received attention due to its role in
neurodegeneration, where mutation of a single copy of GRN, the gene encoding
progranulin, results in frontotemporal dementia, whereas viral delivery of
progranulin to the brains of mice exhibiting Parkinson's or Alzheimer's disease
phenotypes inhibits the progression of the neurodegenerative phenotypes. Of equal
importance, progranulin protects tissues against the harmful effects of poorly
controlled inflammation and promotes tissue regeneration after injury at a
multitude of sites throughout the body. Progranulin is overexpressed by many
types of cancer and contributes to their progression. Given suitable analytical
methods and model systems, progranulin offers a wealth of research possibilities.
PMID- 29956266
TI - Chromatographic Methods for the Purification of Granulin Peptides.
AB - Progranulin is composed of seven repeating cysteine-rich granulin domains. In
some cells and tissues, the progranulin is fragmented by proteolysis to generate
the granulin modules as individual peptides, which are collectively referred to
as granulins. These peptides are often biologically active, but the activity need
not be identical to that of the parental progranulin from which they are derived.
Thus, some granulin peptides stimulate cell proliferation, as does progranulin
itself, while other granulin peptides suppress proliferation. Similarly, some
granulin peptides promote inflammation even though progranulin itself suppresses
inflammation. Investigating the structural and biological properties of granulin
peptides is challenging. Here we discuss methods that employ reversed-phase high
performance liquid chromatography (RP-HPLC) and in some instances size-exclusion
high-performance liquid chromatography (SE-HPLC) to isolate granulin peptides
from tissues, in particular those that are rich in inflammatory cells such as
neutrophils, bone marrow, or hematopoietic organs of teleost fish.
PMID- 29956267
TI - Methods for Expression and Purification of Biologically Active Recombinant
Progranulin.
AB - Purifying progranulin may be useful in a variety of situations, for example,
after it has been mutated or otherwise modified or when working with a species
for which commercially produced progranulin is unavailable. A method to express
and purify human progranulin is presented. Progranulin is transiently expressed
in mammalian cells and isolated from their conditioned medium before purification
by reversed-phase high-performance liquid chromatography (RP-HPLC). Human
progranulin is used as an example, but the protocol can be applied to any other
progranulin protein. Modifications of the expression-purification strategy for
metabolic labeling of progranulin and analytical systems based on heparin
affinity chromatography are presented.
PMID- 29956268
TI - Large-Scale Generation of Recombinant Granulin Peptides in E. coli.
AB - Generating milligram quantities of correctly folded granulin molecules with
properly formed disulfide bonds and biologically relevant activities may
represent a considerable challenge. Here I describe a protocol for obtaining well
folded human granulins A, C, and F by expressing them as thioredoxin fusion
proteins in Origami (DE3) Escherichia coli cells promoting disulfide bond
formation in the cytoplasm environment. The thioredoxin tag is removed by
proteolytic cleavage with enterokinase and granulins which are purified by
reversed-phase HPLC. Well-folded disulfide species display lower retention time
than misfolded species and therefore can be readily purified.
PMID- 29956262
TI - Polychlorinated biphenyls (PCBs) as sentinels for the elucidation of Arctic
environmental change processes: a comprehensive review combined with ArcRisk
project results.
AB - Polychlorinated biphenyls (PCBs) can be used as chemical sentinels for the
assessment of anthropogenic influences on Arctic environmental change. We present
an overview of studies on PCBs in the Arctic and combine these with the findings
from ArcRisk-a major European Union-funded project aimed at examining the effects
of climate change on the transport of contaminants to and their behaviour of in
the Arctic-to provide a case study on the behaviour and impact of PCBs over time
in the Arctic. PCBs in the Arctic have shown declining trends in the environment
over the last few decades. Atmospheric long-range transport from secondary and
primary sources is the major input of PCBs to the Arctic region. Modelling of the
atmospheric PCB composition and behaviour showed some increases in environmental
concentrations in a warmer Arctic, but the general decline in PCB levels is still
the most prominent feature. 'Within-Arctic' processing of PCBs will be affected
by climate change-related processes such as changing wet deposition. These in
turn will influence biological exposure and uptake of PCBs. The pan-Arctic rivers
draining large Arctic/sub-Arctic catchments provide a significant source of PCBs
to the Arctic Ocean, although changes in hydrology/sediment transport combined
with a changing marine environment remain areas of uncertainty with regard to PCB
fate. Indirect effects of climate change on human exposure, such as a changing
diet will influence and possibly reduce PCB exposure for indigenous peoples. Body
burdens of PCBs have declined since the 1980s and are predicted to decline
further.
PMID- 29956269
TI - Nuclear Magnetic Resonance Spectroscopy in Analysis of Granulin Three-Dimensional
Structure and Cysteine Bridging.
AB - Granulin (GRN) structural motif represents a ladderlike stack of beta-hairpins
reinforced with six parallel disulfide bridges. When GRNs are produced in a
recombinant protein expression host (e.g., in bacteria) or via chemical
synthesis, the formation of disulfide bridges from thiols undergoing uncontrolled
oxidation may be random. As a consequence, the resulting protein could be a
mixture of a large number of disulfide species. Incorrectly folded GRNs may
behave abnormally in bioassays; therefore isolation and identification of
properly structured, chemically homogenous GRN peptides is very important for
biological relevance of the GRN effects observed in the tests. Protein nuclear
magnetic resonance (NMR) spectroscopy is an excellent tool for identification and
characterization of well-structured GRN disulfide species produced in an
Escherichia coli expression system. At first, GRN disulfide species are crudely
separated by reversed-phase HPLC chromatography. Obtained fractions are screened
by 1D (one-dimensional) proton NMR for the presence of well-folded GRN species.
The well-folded GRNs are 15N-labeled and purified, and NMR is used to determine
their three-dimensional structure and assign disulfide pairing patterns.
Additionally, NMR characterization of model peptides derived from the GRN amino
acid sequences can help resolve ambiguities in disulfide bond assignment. This
approach was first successfully used to obtain biologically active human GRNs,
but it can be easily expanded to GRN peptides from other species and/or generated
by other methods.
PMID- 29956270
TI - Data Mining: Applying the AD&FTD Mutation Database to Progranulin.
AB - The online AD&FTD Mutation Database ( http://www.molgen.vib-ua.be/FTDmutations )
was conceived to meet the needs of a comprehensive knowledge base of genetic
variations in genes associated with monogenic forms of Alzheimer's disease (AD)
and frontotemporal dementia (FTD). Today, the AD&FTD Mutation Database provides
curated, referenced information of 764 genetic variants in APP, PSEN1, and PSEN2
associated with AD and GRN, C9orf72, TBK1, MAPT, VCP, CHMP2B, TARDBP, and FUS
associated with FTD and related diseases. In addition, the database stores
demographic and clinicogenetic data of 1646 dementia families associated with
these mutations. In FTD, the granulin (GRN) gene has the highest number of
different mutations (79/231 = 34%) and the second highest number of associated
FTD families after C9orf72. In addition to the detailed mutation and patient
information, summary reports in tabular and graphical formats can be consulted.
Further, all variants can be uploaded to the human genome browser for custom
designed analyses.
PMID- 29956271
TI - Measurement of Circulating Progranulin (PGRN/GP88/GEP) by Enzyme-Linked
Immunosorbent Assay and Application in Human Diseases.
AB - The enzyme-linked immunosorbent assay (ELISA) is a well-established methodology
for detection of analytes in various biological fluids. The assay described
herein has been validated for the detection of PGRN/GP88/GEP in blood (serum/
plasma), urine and cerebrospinal fluid (CSF), and synovial fluid and may also be
used for breast milk, ductal lavage, nipple aspirates, and saliva. The ability to
measure circulating levels of PGRN/GP88/GEP has proven to have clinical utility
for several human diseases such as cancer where changes of PGRN/GP88/GEP can be
determined as a mean to monitor disease status or response to therapy. In the
case of frontotemporal dementia (FTD), the ability to measure PGRN/GP88/GEP
levels in plasma and cerebrospinal fluid may be useful in distinguishing PGRN
mutation carriers among FTD populations at large. The assay used is a sandwich
ELISA where a highly specific antihuman PGRN/GP88/GEP monoclonal antibody is
employed as a capture antibody coated on 96-well microplates. After contact with
serum (or other bodily fluid), unbound material is washed away before application
of another PGRN/GP88/GEP detecting antibody which in turn is detected by a
horseradish peroxidase (HRP) conjugated antibody. After further washing to remove
all unbound HRP, a substrate (TMB) is added, and after approximately 6 min, a
color is developed and can be read as optical density at 620 nm (or 450 nm if
using HCL as a stop solution) in a microplate reader. The test described herein
is capable of measuring very low levels of PGRN/GP88/GEP such as 0.2 ng/mL as
found in CSF of certain FTD patients. Additionally, we have demonstrated the
potential clinical utility of measuring the changes of PGRN/GP88/GEP blood levels
in cancer patients undergoing therapy.
PMID- 29956272
TI - Immunohistochemical Detection of Progranulin (PGRN/GP88/GEP) in Tumor Tissues as
a Cancer Prognostic Biomarker.
AB - Immunohistochemistry is a well characterized and robust staining technique for
the identification and localization of proteins in biological tissues. The
following methodology describes the process for identifying progranulin
(PGRN/GP88/GEP) in the cellular cytoplasm of target tissues such as tumor
biopsies. Such tissue is collected from cancer patients and stabilized using
formalin-fixed paraffin embedding after which 4-5 MUm sections of the tissue are
mounted on positively charged microscope slides. After deparaffinization using
ethanol, the tissue is processed through an antigen retrieval process using
citric acid at pH 6.4. A monoclonal antibody (Clone AG03) against human
PGRN/GP88/GEP is then contacted with the tissue before a horseradish peroxidase
(HRP) conjugated antibody is employed to detect AG03 bound to PGRN/GP88/GEP.
Subsequent application of the HRP substrate results in color generation. Using a
light microscope, a trained user can "score" the percentage of cells stained and
intensity of such staining. Scoring ranges from 0 (no staining) to 3+ (strong
cytoplasmic staining in >10% tumor cells). When scoring is correlated to patient
outcome, we have demonstrated that a patient with tumor PGRN/GP88/GEP staining of
"3+" has a fivefold increased risk of disease recurrence within 5 years.
PMID- 29956273
TI - Analysis of Progranulin-Mediated Akt and MAPK Activation.
AB - Progranulin has emerged in recent years as an important regulator of various
biological functions including cell proliferation, wound healing, motility, and
protection from apoptosis. Progranulin is also critical for transformation as
established in several cancer models.Progranulin biological responses elicit
through the activation of the Akt and MAPK pathways, which are critical for
progranulin downstream signaling.In this chapter various experimental approaches
aiming at detecting progranulin-mediated Akt and MAPK activation will be
discussed.
PMID- 29956274
TI - Mouse Monoclonal Antibodies Against Progranulin (PGRN/GEP) as Therapeutics in
Preclinical Cancer Models.
AB - The use of monoclonal antibody (mAb) has become a unique means of targeted
therapy for human cancers. mAb-based therapies have shown survival benefits by
applying alone or in combination with chemotherapeutics. Being a humanized
biomolecule with exquisite target specificity, mAb demonstrated effects in a
relatively lower dose range with limited off-target harm to the patients.
Nowadays, novel targets involved in tumorigenic mechanisms and biomarkers
expressed exclusively on cancer cell surface are being constantly discovered. The
potential effects of their specific mAb could be investigated in the preclinical
cancer model. In this chapter, we outlined our experimental procedures in
determining the feasibility of novel mAb in the preclinical cancer model, with an
example of progranulin (PGRN/GEP) mAb against hepatocellular carcinoma (HCC)
tumor in mouse model. This chapter included the establishment of subcutaneous and
orthotopic HCC tumor in mouse model, the injection of the mouse monoclonal
antibody in combination with cytotoxic chemotherapeutics, the assessment of tumor
development, and the analyses of the molecular changes of the tumor cells.
PMID- 29956275
TI - Methods to Analyze the Role of Progranulin (PGRN/GEP) on Cancer Stem Cell
Features.
AB - Emerging evidence suggests that tumors are hierarchically organized with a
distinct subpopulation called cancer stem cells (CSCs) lying at the apex of the
hierarchy. These cells are not only responsible for tumor initiation and
progression but also endowed with stem cell properties, including self-renewal,
chemoresistance, and tumor initiation. Although existing therapies can initially
eliminate the bulk population of tumor, the stem cell properties of CSCs enable
them to survive and repopulate the tumor, resulting in disease relapse. Recently,
our group has shown that progranulin (PGRN/GEP) defined a hepatic cancer stem
cell subpopulation in hepatocellular carcinoma. This subpopulation demonstrated
enhanced ability for colony and spheroid formation, chemoresistance, and tumor
initiation. In this chapter, we describe the methods used to isolate the
progranulin+ subpopulation and analyze their CSC properties.
PMID- 29956276
TI - Methods to Study the Role of Progranulin in the Tumor Microenvironment.
AB - Accurate measurement of progranulin (PGRN) in the circulation and in the tumor
microenvironment is essential for understanding its role in cancer progression
and metastasis. This chapter describes a number of approaches to measure the
transcription level of the GRN gene and to detect and analyze PGRN expression in
cancer cells and in the local environment of the tumor, in mouse and human
samples. These validated protocols are utilized to investigate the functional
role of PGRN in cancer. Finally, we discuss strategies to investigate the
functions of PGRN in tumors using genetically modified mouse models and gene
silencing techniques.
PMID- 29956277
TI - Methods to Investigate the Molecular Basis of Progranulin Action on Neurons In
Vivo Using Caenorhabditis elegans.
AB - The C. elegans nematode is a powerful genetic tool for the study of aging,
developmental biology, and neurodegenerative diseases. They are a small and
simple model, but its well-known genome and presence of many human orthologs has
made it an ideal model to study the effects of PGRN in vivo. Here, we will
describe the protocols used by our laboratory to study how PGRN affects C.
elegans neuronal morphology and locomotion behavior through the use of a loss-of
function model of the nematode otholog of the GRN gene, pgrn-1. Although these
protocols have been used by us to specifically study the pgrn-1 gene, the
experiments are applicable to any of the animal's genes.
PMID- 29956278
TI - The Use of Caenorhabditis elegans to Study Progranulin in the Regulation of
Programmed Cell Death and Stress Response.
AB - The nematode Caenorhabditis elegans (C. elegans) has proven to be a powerful
model organism for the study of many biological processes, with major
implications for human health and disease. As progranulin is a pleiotropic,
secreted protein with both cell autonomous and non-autonomous roles, a
multicellular organism such as C. elegans is ideal for the investigation of its
normal function and pathological effects. The C. elegans genome contains a
progranulin-like gene known as pgrn-1. The nematode pgrn-1 encodes a protein with
three cysteine-rich granulin domains, compared to the seven and a half granulins
in the human protein. We have shown that C. elegans mutants lacking pgrn-1 appear
grossly normal, but exhibit accelerated apoptotic cell engulfment as well as a
stress resistance phenotype (Kao et al., Proc Natl Acad Sci U S A 108:4441-4446,
2011; Judy et al., PLoS Genet 9:e1003714, 2013). In addition, the roles of
individual granulins can also be dissected in C. elegans (Salazar et al., J
Neurosci 35:9315-9328, 2015). Here, we describe methods for studying apoptosis
and stress response in C. elegans.
PMID- 29956279
TI - Application of Zebrafish and Knockdown Technology to Define Progranulin Neuronal
Function.
AB - The zebrafish (Danio rerio), a small tropical fish, has become a powerful model
for the study of early vertebrate development, human diseases, and drug
screening. Zebrafish provides large numbers of optically clear embryos, and its
development is very rapid. Overexpression or under-expression of proteins can be
effectively achieved by microinjection of mRNA or morpholino antisense
oligonucleotides (MOs), respectively, into developing embryos at the 1-2 cell
stage. The function of a particular protein can be revealed by correlating gene
expression patterns with the phenotypes observed from over- or under-expression.
We defined the expression pattern of zebrafish progranulin A (zfPGRN-A), an
orthologue to the single human PGRN by whole-mount in situ hybridization (ISH)
and immunofluorescence (IF). The MO-mediated knockdown of zfPGRN-A expression
generated embryos that display abnormal motor neuron development resulting in
touch-evoked swimming deficits.
PMID- 29956280
TI - Methods to Investigate the Molecular Basis of Progranulin Actions on Brain and
Behavior In Vivo Using Knockout Mice.
AB - Currently one of the few molecules that equally excites a neuroscientist, a
cancer biologist, an immunologist, and a developmental biologist is progranulin
(GRN/Grn)-a pluripotent growth factor that plays key roles in cell survival,
proliferation, development, tissue regeneration, inflammation, wound healing, and
angiogenesis. However, the molecular pathways associated with GRN signaling
involved in these varied physiological processes are not understood. Gene
inactivation has been considered as one of the best methods to delineate the
biological role of a protein, and gene targeting is a direct means to disrupt a
gene's open reading frame and block its expression, for instance, in a mouse.
Such a gene knockout animal model also served as an in vivo disease model where
loss of gene or its function is thought to be the primary disease mechanism, as
is the case with progranulin loss of function in frontotemporal lobar
degeneration (FTLD). It is estimated that up to half of the cases of familial,
dominant FTLD might be due to GRN haploinsufficiency. To understand the molecular
pathways associated with GRN loss, constitutive and conditional progranulin
knockout (Grn-/-) mice have also been constructed in several laboratories,
including ours. These mice show several disease-characteristic features and
suggest that continued studies on the Grn-/- mice would be instructive in the
understanding of complex GRN biology in health and disease.
PMID- 29956281
TI - Methods to Investigate the Protection Against Neurodegenerative Disorders
Provided by Progranulin Gene Transfer in the Brain.
AB - Progranulin (PGRN) is a multifunctional protein that is widely expressed
throughout the brain, where it has been shown to be a critical regulator of CNS
inflammation (Ahmed et al., J Neuroinflammation 4:7, 2007; Yin et al., J Exp Med
207:117-128, 2010; Martens et al., J Clin Investig 122:3955-3959; Inestrosa and
Arenas). PGRN functions as an autocrine neuronal growth factor, important for
long-term neuronal survival (Ahmed et al., J Neuroinflammation 4:7, 2007; Nat Rev
Neurosci 11:77-86, 2009). Together, these critical roles in the CNS suggest that
enhancing PGRN expression may provide neuronal support and protection for
neurodegenerative disorders, such as Parkinson's disease (PD). Here, we describe
the application of PGRN gene transfer using in vivo delivery of lentiviral
expression vectors in a rodent model of PD.
PMID- 29956282
TI - The Interaction Between Progranulin with Sortilin and the Lysosome.
AB - Accumulating evidence suggests that progranulin is essential for proper lysosomal
function. Progranulin is a lysosomal resident protein and sortilin has been
demonstrated to be the lysosomal trafficking receptor for progranulin. Here we
describe the methods used to study the interaction between progranulin and
sortilin, as well as the critical role of sortilin in mediating the lysosomal
delivery of progranulin.
PMID- 29956283
TI - Methods to Study the Role of Progranulin in Preimplantation Mouse Embryo
Development.
AB - Progranulin is a 67-88 kDa glycoprotein, also known as acrogranin, PC-cell
derived growth factor, granulin-epithelin precursor, and proepithelin. This
protein is present in a variety of mouse, rat, and human tissues. Progranulin,
which is a growth factor, mediates cell cycle progression and cell migration in
normal and pathological conditions. In several types of cancers, progranulin
expression is upregulated, whereas function-interfering mutations in the granulin
gene in humans have been linked to a subset of heritable cases of frontotemporal
lobar degeneration. Also, progranulin has important effects on mouse
preimplantation embryo development in vitro, including regulation of the
appearance of the epithelium in the developing mouse blastocyst and growth of
trophectoderm. Furthermore, progranulin promotes mouse blastocyst hatching,
adhesion, and outgrowth in vitro. In this chapter, we describe some of the
techniques that may be useful in the study of progranulin in embryo development.
PMID- 29956284
TI - Establishment of a Modified Collagen-Induced Arthritis Mouse Model to Investigate
the Anti-inflammatory Activity of Progranulin in Inflammatory Arthritis.
AB - Progranulin (PGRN) was found to play an anti-inflammatory and protective role in
both inflammatory and degenerative arthritis (Tang et al., Science 332:478-484,
2011; Zhao et al., Ann Rheum Dis 74:2244-2253, 2015). We recently published a
visualized protocol to demonstrate a surgically-induced mouse model for examining
the protective role of PGRN in degenerative osteoarthritis (Zhao et al., J Vis
Exp:e50924, 2014). Herein we describe a modified collagen-induced arthritis (CIA)
mouse model to investigate the anti-inflammatory activity of PGRN in inflammatory
arthritis. CIA model is the most commonly used autoimmune model of inflammatory
arthritis which shares both immunological and pathological features with human
rheumatoid arthritis. Autoimmune inflammatory arthritis is induced by
immunization with an emulsion of complete Freund's adjuvant and chicken type II
collagen (CII) using a modified procedure in PGRN deficient mice and control
littermates. Using the protocol described here, the investigator should be able
to reproducibly induce a high incidence of CIA in PGRN deficient mice and also
learn how to critically evaluate the severity and incidence of this disease
model.
PMID- 29956285
TI - Methods for Studying the Function of Progranulin in Atherosclerosis Using Both
Knockout Mice Models and In Vitro Studies.
AB - Progranulin (PGRN) has been reported to be associated with cell proliferation,
cell growth, wound healing, and inflammation. PGRN mutations are known to be
related to dementia. However, the association between PGRN and atherosclerosis
remains to be elucidated. Therefore, we generated PGRN-/-ApoE-/- mice to analyze
the effect of PGRN on the development of atherosclerosis.
PMID- 29956286
TI - Methods to Investigate the Roles of Progranulin in Angiogenesis Using In Vitro
Strategies and Transgenic Mouse Models.
AB - Endothelial cells activate the expression of progranulin during angiogenesis.
Here we discuss methods to investigate progranulin activity on endothelial cells
in vitro and on aortic explants. We then discuss methods to generate transgenic
mice in which progranulin expression is targeted to endothelial cells. These mice
can be used to study the influence of progranulin on angiogenesis during
development in vivo. The transgenic strategy summarized here could be readily
adapted to investigate the roles of progranulin in other cell types and tissues
by use of appropriate targeting vectors to drive the expression of progranulin in
the cell type of choice.
PMID- 29956287
TI - Historical and Clinical Perspectives on Chromosomal Translocations.
AB - Chromosomal translocations, rearrangements involving the exchange of segments
between chromosomes, were documented in humans in 1959. The first accurately
reported clinical phenotype resulting from a translocation was that of Down
syndrome. In a small percentage of Down syndrome cases, an extra 21q is provided
by a Robertsonian translocation chromosome, either occurring de novo or inherited
from a phenotypically normal parent with the translocation chromosome and a
balanced genome of 45 chromosomes. Balanced translocations, including both
Robertsonian and reciprocal translocations, are typically benign, but meiosis in
germ cells with balanced translocations may result in meiotic arrest and
subsequent infertility, or in unbalanced gametes, with attendant risks of
miscarriage and unbalanced progeny. Most reciprocal translocations are unique. A
few to several percent of translocations disrupt haploinsufficient genes or their
regulatory regions and result in clinical phenotypes. Balanced translocations
from patients with clinical phenotypes have been valuable in mapping disease
genes and in illuminating cis-regulatory regions. Mapping of discordant mate
pairs from long-insert, low-pass genome sequencing now permits efficient and cost
effective discovery and nucleotide-level resolution of rearrangement breakpoints,
information that is absolutely necessary for interpreting the etiology of
clinical phenotypes in patients with rearrangements. Pathogenic translocations
and other balanced chromosomal rearrangements constitute a class of typically
highly penetrant mutation that is cryptic to both clinical microarray and exome
sequencing. A significant proportion of rearrangements include additional
complexity that is not visible by conventional karyotype analysis. Some
proportion of patients with negative findings on exome/genome sequencing and
clinical microarray will be found to have etiologic balanced rearrangements only
discoverable by genome sequencing with analysis pipelines optimized to recover
rearrangement breakpoints.
PMID- 29956288
TI - Induction of Chromosomal Translocations with CRISPR-Cas9 and Other Nucleases:
Understanding the Repair Mechanisms That Give Rise to Translocations.
AB - Chromosomal translocations are associated with several tumor types, including
hematopoietic malignancies, sarcomas, and solid tumors of epithelial origin, due
to their activation of a proto-oncogene or generation of a novel fusion protein
with oncogenic potential. In many cases, the availability of suitable human
models has been lacking because of the difficulty in recapitulating precise
expression of the fusion protein or other reasons. Further, understanding how
translocations form mechanistically has been a goal, as it may suggest ways to
prevent their occurrence. Chromosomal translocations arise when DNA ends from
double-strand breaks (DSBs) on two heterologous chromosomes are improperly
joined. This review provides a summary of DSB repair mechanisms and their
contribution to translocation formation, the various programmable nuclease
platforms that have been used to generate translocations, and the successes that
have been achieved in this area.
PMID- 29956289
TI - Dynamics of Double-Strand Breaks: Implications for the Formation of Chromosome
Translocations.
AB - Illegitimate joining of chromosome breaks can lead to the formation of chromosome
translocations, a catastrophic type of genome rearrangements that often plays key
roles in tumorigenesis. Emerging evidence suggests that the mobility of broken
DNA loci can be an important determinant in partner search and clustering of
individual breaks, events that can influence translocation frequency. We
summarize here the recent literature on the mechanisms that regulate chromatin
movement, focusing on studies exploring the motion properties of double-strand
breaks in the context of chromatin, the functional consequences for DNA repair,
and the formation of chromosome fusions.
PMID- 29956290
TI - The CRISPR/Cas9 System as a Tool to Engineer Chromosomal Translocation In Vivo.
AB - The CRISPR/Cas9 system has emerged as a powerful tool to edit the genome. Among
many applications, the system generates the exciting possibility of engineering
small and large portions of chromosomes to induce a variety of structural
alterations such as deletions, inversions, insertions and inter-chromosomal
translocations. Furthermore, the availability of viral vectors that express Cas9
has been critical to deliver the CRISPR/Cas9 system directly in vivo to induce
chromosomal rearrangements. This review provides an overview of the state-of-the
art CRISPR/Cas9 technology to model a variety of rearrangements in vivo in animal
models.
PMID- 29956291
TI - Generation of Genomic Alteration from Cytidine Deamination.
AB - The sources of genome instability can be attributed to many extra- and exo-
cellular factors accompanying various biological processes. In leukemia and
lymphomas, the collateral effect of programmed DNA alterations during immune
diversification is the major source of genome instability. Cytidine deamination
from cytidine (C) to uridine (U) at immunoglobulin (Ig) gene loci is required for
initiation of antibody diversification, while the same process also contributes
to recurrent translocation or mutations outside of Ig loci in lymphocyte-origin
tumors. Furthermore, genome sequencing of cancer cells from many tissue origins
revealed a significant enrichment of cytidine deaminase mutagenesis signature in
human cancers. Thus, cytidine deamination, which can intensively happen in an
enzyme-dependent fashion at specific genomic regions, is a widespread genome
instability source across many tumor types. AID/APOBEC superfamily proteins are
the main single-stranded DNA deaminases in eukaryotes, which play vital roles in
adaptive and innate immunity. Their deamination products can be channeled into
mutations, insertions and deletions (indels), clusters of mutations called
kaetagis, or chromosomal rearrangements/translocations. Here, we review the
generation of genome instability from AID/APOBEC-dependent cytidine deamination
with emphasis on the most studied enzyme, AID.
PMID- 29956292
TI - The Role for the DSB Response Pathway in Regulating Chromosome Translocations.
AB - In response to DNA double strand breaks (DSB), mammalian cells activate the DNA
Damage Response (DDR), a network of factors that coordinate their detection,
signaling and repair. Central to this network is the ATM kinase and its
substrates at chromatin surrounding DSBs H2AX, MDC1 and 53BP1. In humans,
germline inactivation of ATM causes Ataxia Telangiectasia (A-T), an autosomal
recessive syndrome of increased proneness to hematological malignancies driven by
clonal chromosomal translocations. Studies of cancers arising in A-T patients and
in genetically engineered mouse models (GEMM) deficient for ATM and its
substrates have revealed complex, multilayered roles for ATM in translocation
suppression and identified functional redundancies between ATM and its substrates
in this context. "Programmed" DSBs at antigen receptor loci in developing
lymphocytes employ ubiquitous DDR factors for signaling and repair and have been
particularly useful for mechanistic studies because they are region-specific and
can be monitored in vitro and in vivo. In this context, murine thymocytes
deficient for ATM recapitulate the molecular events that lead to transformation
in T cells from A-T patients and provide a widely used model to study the
mechanisms that suppress RAG recombinase-dependent translocations. Similarly,
analyses of the fate of Activation induced Cytidine Deaminase (AID)-dependent
DSBs during mature B cell Class Switch Recombination (CSR) have defined the
genetic requirements for end-joining and translocation suppression in this
setting. Moreover, a unique role for 53BP1 in the promotion of synapsis of
distant DSBs has emerged from these studies.
PMID- 29956293
TI - Telomeres and Chromosomal Translocations : There's a Ligase at the End of the
Translocation.
AB - Chromosomal translocations are now well understood to not only constitute
signature molecular markers for certain human cancers but often also to be
causative in the genesis of that tumor. Despite the obvious importance of such
events, the molecular mechanism of chromosomal translocations in human cells
remains poorly understood. Part of the explanation for this dearth of knowledge
is due to the complexity of the reaction and the need to archaeologically work
backwards from the final product (a translocation) to the original unrearranged
chromosomes to infer mechanism. Although not definitive, these studies have
indicated that the aberrant usage of endogenous DNA repair pathways likely lies
at the heart of the problem. An equally obfuscating aspect of this field,
however, has also originated from the unfortunate species-specific differences
that appear to exist in the relevant model systems that have been utilized to
investigate this process. Specifically, yeast and murine systems (which are often
used by basic science investigators) rely on different DNA repair pathways to
promote chromosomal translocations than human somatic cells. In this chapter, we
will review some of the basic concepts of chromosomal translocations and the DNA
repair systems thought to be responsible for their genesis with an emphasis on
underscoring the differences between other species and human cells. In addition,
we will focus on a specific subset of translocations that involve the very end of
a chromosome (a telomere). A better understanding of the relationship between DNA
repair pathways and chromosomal translocations is guaranteed to lead to improved
therapeutic treatments for cancer.
PMID- 29956294
TI - 3D Genome Organization Influences the Chromosome Translocation Pattern.
AB - Recent imaging, molecular, and computational modeling studies have greatly
enhanced our knowledge of how eukaryotic chromosomes are folded in the nuclear
space. This work has begun to reveal how 3D genome structure contributes to
various DNA-mediated metabolic activities such as replication, transcription,
recombination, and repair. Failure of proper DNA repair can lead to the
chromosomal translocations observed in human cancers and other diseases.
Questions about the role of 3D genome structure in translocation mechanisms have
interested scientists for decades. Recent applications of imaging and Chromosome
Conformation Capture approaches have clarified the influence of proximal
positioning of chromosomal domains and gene loci on the formation of chromosomal
translocations. These approaches have revealed the importance of 3D genome
structure not only in translocation partner selection, but also in repair
efficiency, likelihood of DNA damage, and the biological implications of
translocations. This chapter focuses on our current understanding of the role of
3D genome structure in chromosome translocation formation and its potential
implications in disease outcome.
PMID- 29956295
TI - The Role of Chromosome Deletions in Human Cancers.
AB - Chromosome deletions are a hallmark of human cancers. These chromosome
abnormalities have been observed for over than a century and frequently
associated with poor prognosis. However, their functions and potential underlying
mechanisms remain elusive until recently. Recent technique breakthroughs,
including cancer genomics, high throughput library screening and genome editing,
opened a new era in the mechanistic studying of chromosome deletions in human
cancer. In this chapter, we will focus on the latest studies on the functions of
chromosome deletions in human cancers, especially hematopoietic malignancies and
try to persuade the readers that these chromosome alterations could play
significant roles in the genesis and drug responses of human cancers.
PMID- 29956296
TI - Processing-Challenges Generated by Clusters of DNA Double-Strand Breaks Underpin
Increased Effectiveness of High-LET Radiation and Chromothripsis.
AB - Whereas most endogenous and exogenous DNA damaging agents typically generate
lesions that are relatively isolated and can be repaired easily, ionizing
radiation (IR) also induces clustered lesions causing DNA double strand breaks
(DSBs). Moreover, forms of IR characterized by high linear energy transfer (LET)
induce not only isolated DSBs but also DSB clusters - multiple DSBs in close
proximity -that pose increased risks for the cell. DSB clusters can destabilize
chromatin locally and compromise processing of individual DSBs within the
cluster. Since the discovery of chromothripsis, a phenomenon whereby multiple
DSBs locally generated by a catastrophic event causes genomic rearrangements that
feed carcinogenesis, DSB clusters receive increased attention also in the field
of cancer. While formation of DSB clusters after exposure to high LET is a direct
and inherent consequence of the spatial distribution of the constituting energy
deposition events, also called track structure, the sources of local genomic
shattering underpinning chromothripsis are under investigation. Notably, many
consequences of DSB clusters in the affected genome reflect processing by
pathways that have evolved to repair DSBs, but which operate with widely
different degrees of fidelity. The molecular underpinnings and the basis of the
underlying repair pathway choices that ultimately lead to the observed
consequences from DSB clusters remain unknown. We developed a tractable model of
DSB clustering that allows direct analysis in cells of the consequences of
certain configurations of DSB clusters. We outline the rationale for the
development of this model and describe its key characteristics. We summarize
results suggesting that DSB clusters compromise the first-line DSB-processing
pathways of c-NHEJ and HRR, increasing as a consequence the contribution of alt
EJ, which has high propensity of generating chromosomal rearrangements. The
results suggest a mechanism for the increased toxicity of high LET radiation and
the extensive genomic rearrangements associated with chromothripsis.
PMID- 29956298
TI - Altered myelination in the Niemann-Pick type C1 mutant mouse.
AB - Niemann-Pick type C1 (NPC1) disease is a lysosomal storage disorder caused by
mutation of Npc1 or Npc2 gene, resulting in various progressive pathological
features. Myelin defection is a major pathological problem in Npc1 mutant mice;
however, impairment of myelin proteins in the developing brain is still
incompletely understood. In this study, we showed that the expression of myelin
genes and proteins is strongly inhibited from postnatal day 35 onwards including
reduced myelin basic protein (MBP) expression in the brain. Furthermore,
myelination characterized by MBP immunohistochemistry was strongly perturbed in
the forebrain, moderately in the midbrain and cerebellum, and slightly in the
hindbrain. Our results demonstrate that mutation of the Npc1 gene is sufficient
to cause severe and progressive defects in myelination in the mouse brain.
PMID- 29956297
TI - Technology Informatics Guiding Education Reform - TIGER.
AB - BACKGROUND: While health informatics recommendations on competencies and
education serve as highly desirable corridors for designing curricula and
courses, they cannot show how the content should be situated in a specific and
local context. Therefore, global and local perspectives need to be reconciled in
a common framework. OBJECTIVES: The primary aim of this study is therefore to
empirically define and validate a framework of globally accepted core competency
areas in health informatics and to enrich this framework with exemplar
information derived from local educational settings. METHODS: To this end, (i) a
survey was deployed and yielded insights from 43 nursing experts from 21
countries worldwide to measure the relevance of the core competency areas, (ii) a
workshop at the International Nursing Informatics Conference (NI2016) held in
June 2016 to provide information about the validation and clustering of these
areas and (iii) exemplar case studies were compiled to match these findings with
the practice. The survey was designed based on a comprehensive compilation of
competencies from the international literature in medical and health informatics.
RESULTS: The resulting recommendation framework consists of 24 core competency
areas in health informatics defined for five major nursing roles. These areas
were clustered in the domains "data, information, knowledge", "information
exchange and information sharing", "ethical and legal issues", "systems life
cycle management", "management" and "biostatistics and medical technology", all
of which showed high reliability values. The core competency areas were ranked by
relevance and validated by a different group of experts. Exemplar case studies
from Brazil, Germany, New Zealand, Taiwan/China, United Kingdom (Scotland) and
the United States of America expanded on the competencies described in the core
competency areas. CONCLUSIONS: This international recommendation framework for
competencies in health informatics directed at nurses provides a grid of
knowledge for teachers and learner alike that is instantiated with knowledge
about informatics competencies, professional roles, priorities and practical,
local experience. It also provides a methodology for developing frameworks for
other professions/disciplines. Finally, this framework lays the foundation of
cross-country learning in health informatics education for nurses and other
health professionals.
PMID- 29956299
TI - Foetal goitrous hypothyroidism - easy to recognise, difficult to treat. Is
combined intra-amniotic and intravenous L-thyroxine therapy an option?
AB - INTRODUCTION: Foetal hypothyroidism negatively impacts somatic and neurological
child development and can be the cause of serious obstetric and perinatal
complications. We present a rare case of a large foetal dyshormonogenetic goitre,
causing foetal neck hyperexten-sion, oesophageal compression, and cardiac high
output failure. MATERIAL AND METHODS: A foetal goitre complicated by cardiomegaly
and polyhydramnios was diagnosed at 23 weeks of gestation (WG) on a routine
ultrasonographic (US) assessment in a healthy nullipara. Foetal blood sampling
was performed and a severe foetal hypothyroid-ism was diagnosed. Treatment was
undertaken with an intra-amniotic followed by combined intra-amniotic and
intravenous injections of L-thyroxine (L-T4). A total of 11 doses of L-T4 were
administered between 24-37 WG to the foetus. RESULTS: A complete regression of
foetal goitre, cardiomegaly, and polyhydramnios was observed. At 38 WG the
patient delivered vagi-nally a male infant with mild hypothyroidism and no signs
of goitre or cardiomegaly on postnatal US. Neurological development of the one
year old baby is normal. CONCLUSIONS: The effective diminishing of serum TSH
concentration and goitre size was reached after combined intra-amniotic and in
travenous L-T4 injections were given. L-T4 requirement in the foetus is equal to
or above 15 MUg/kg daily and should be given in weekly intervals due to its rapid
metabolism by the foetus and by placental type 3 deiodinase. Intra-amniotic L-T4
administration may be inef-fective when a large goitre indisposes amniotic fluid
swallowing by the foetus, so then the combined L-T4 injections into the umbilical
vein and intra-amniotically in experienced hands seems to be a reasonable and
effective option.
PMID- 29956300
TI - Maternal mortality in Italy: Results and perspectives of record-linkage analysis.
AB - INTRODUCTION: Accurate estimates and reliable classification of maternal deaths
are imperative steps in the chain of actions targeted at reducing avoidable
maternal mortality. The aims of this study were to estimate the maternal
mortality ratio (MMR) in 10 Italian regions covering 77% of total national births
and to identify the most suitable approach to classify the causes of death.
MATERIAL AND METHODS: Deaths during and within 1 year after pregnancy have been
identified through linkage between death registry and hospital discharge
database. Regional and national data sources from 2006 to 2012 were used. The MMR
has been estimated and deaths were classified as direct or indirect and according
to their primary causes. RESULTS: A total of 277 maternal deaths within 42 days
after pregnancy were identified: 149 direct, 102 indirect causes and 26
unclassified-resulting in a MMR of 9.18 per 100 000 live births. The under
reporting rate of official MMR figures in the participating regions is 60.3%.
Hemorrhage (MMR 1.92), hypertensive disorders of pregnancy and cardiac diseases
(MMR 1.06) were the leading causes of deaths occurring within 42 days after
pregnancy, whereas malignancy (39%) and violent deaths (17%) were the most
frequent of the 543 late maternal deaths. CONCLUSIONS: Record-linkage is an
efficient and reliable method to estimate maternal mortality and to identify
causes of maternal deaths. Both the indirect/direct and the classification by
primary cause have a role in countries where direct deaths exceed indirect
maternal mortality. Building upon linkage data, confidential enquiries further
increase the likelihood of reducing maternal mortality.
PMID- 29956301
TI - Benign paroxysmal torticollis of infancy does not lead to neurological sequelae.
AB - AIM: To elucidate the natural course of benign paroxysmal torticollis, the
relationship of this disorder to migraine and other paroxysmal diseases, and to
analyse candidate genes. METHOD: This was a case series of children with benign
paroxysmal torticollis of infancy (BPTI) diagnosed from 1998 to 2005, at Astrid
Lindgren Children's Hospital, Stockholm, Sweden. A neurological examination and a
formalized motor assessment were performed from 2005 to 2007. At a second follow
up, in 2014 to 2015, the children and their parents were interviewed and
candidate genes analysed. RESULTS: The mean age of the eight females and three
males included in the second follow-up was 13 years 9 months (SD 2y 2mo). All
motor assessments were normal. Five had developed migraine, abdominal migraine,
and/or cyclic vomiting. Prophylactic treatment or migraine-specific medication
during attacks were not needed. No paroxysmal tonic upgaze, benign paroxysmal
vertigo, epilepsy, episodic ataxia, or paroxysmal dyskinesia was reported. Rare
genetic variants in CACNA1A and ATP1A2 were found in two children. Five had a
family history of migraine. INTERPRETATION: BPTI is transient and does not lead
to neurological sequelae. Most children afflicted experience either a mild
migraine or no paroxysmal disorder at all in their adolescence. Genetic variants
in candidate genes were few, indicating potential genetic heterogeneity. WHAT
THIS PAPER ADDS: After resolution of their benign paroxysmal torticollis of
infancy (BPTI), children display no gross motor delay. Most adolescents who
previously had BPTI have not developed migraine. No mutations in candidate genes,
known to cause hemiplegic migraine, were found. Associated symptoms are often
lacking during episodes of torticollis.
PMID- 29956302
TI - Strategies to reduce global maternal mortality requires political will and
investment in grassroots level-healthcare workers.
PMID- 29956303
TI - An explanation for the mysterious distribution of melanin in human skin: a rare
example of asymmetric (melanin) organelle distribution during mitosis of basal
layer progenitor keratinocytes.
AB - BACKGROUND: Melanin is synthesized by melanocytes in the basal layer of the
epidermis. When transferred to surrounding keratinocytes melanin is the key
ultraviolet radiation-protective biopolymer responsible for skin pigmentation.
Most melanin is observable in the proliferative basal layer of the epidermis and
only sparsely distributed in the stratifying/differentiating epidermis. The
latter has been explained as 'melanin degradation' in suprabasal layers.
OBJECTIVES: To re-evaluate the currently accepted basis for melanin distribution
in human epidermis and to discover whether this pattern is altered after a
regenerative stimulus. METHODS: Normal epidermis of adult human skin, at rest and
after tape-stripping, was analysed by a range of (immuno)histochemical and high
resolution microscopy techniques. In vitro models of melanin granule uptake by
human keratinocytes were attempted. RESULTS: We propose a different fate for
melanin in the human epidermis. Our evidence indicates that the bulk of melanin
is inherited only by the nondifferentiating daughter cell postmitosis in
progenitor keratinocytes via asymmetric organelle inheritance. Moreover, this
preferred pattern of melanin distribution can switch to a symmetric or equal
daughter cell inheritance mode under conditions of stress, including
regeneration. CONCLUSIONS: In this preliminary report, we provide a plausible and
histologically supported explanation for how human skin pigmentation is
efficiently organized in the epidermis. Steady-state epidermis pigmentation may
involve much less redox-sensitive melanogenesis than previously thought, and at
least some premade melanin may be available for reuse. The epidermal melanin unit
may be an excellent example with which to study organelle distribution via
asymmetric or symmetric inheritance in response to microenvironment and tissue
demands.
PMID- 29956305
TI - It is time to start taking tobacco seriously as a risk factor for psychosis: self
medication cannot explain the association.
PMID- 29956304
TI - Otolith development in wild populations of stickleback: Jones & Hynes method does
not apply to most populations.
AB - This paper critiques Jones & Hynes (1950) findings by analysing sequential
samples of otoliths from three wild populations of Gasterosteus aculeatus from
North Uist, Scotland and Nottingham, England. Contrary to Jones & Hynes (1950),
but coincident with the finding of later researchers, our results showed that no
true translucent ring formed in the otolith of G. aculeatus during their first
summer. The first translucent ring was probably starting to be formed by the end
of summer and was completed by the end of their first winter. There was no second
opaque ring in the otoliths of G. aculeatus before they passed their first
winter. The second opaque ring was just starting to appear by early April of the
second year in the southern population i.e. Nottingham, but later, by May, in the
northern populations i.e. North Uist. Formation of the opaque ring in G.
aculeatus mostly occurs in spring and summer, with younger fish starting earlier.
In contrast, the formation of translucent rings is mostly during autumn and
winter, but can be more widespread through the year, possibly as a result of
reproductive investment.
PMID- 29956306
TI - Is it time for a more nuanced view on self-admission to in-patient treatment in
psychiatry?
PMID- 29956307
TI - Investigations of pupillary responses in depression.
PMID- 29956309
TI - The Scottish invasion of pink salmon in 2017.
PMID- 29956308
TI - Association of the whale shark Rhincodon typus with the cannonball jellyfish
Stomolophus meleagris.
AB - This study describes the first record of the whale shark Rhincodon typus
association with the cannonball jellyfish Stomolophus meleagris in the Gulf of
California, Mexico. Whale sharks were observed swimming and feeding among swarms
of jellyfish, suggesting competition and predatory behaviour given the overlap in
food preferences between both species. This finding is relevant because of the
species-wide distribution and the importance of these interactions, which should
be considered in conservation strategies of R. typus and management of cannonball
jellyfish fisheries.
PMID- 29956310
TI - Paediatric pain management: knowledge, attitudes, barriers and facilitators among
nurses - integrative review.
AB - AIMS: To identify and synthesize evidence regarding the knowledge and attitudes
of nurses, and barriers and facilitators to effective pain assessment and
management in infants and children. BACKGROUND: Pain among children is a common
experience. Relief from pain is a fundamental human right, yet hospitalized
children continue to experience unrelieved pain. Provision of effective pain
management is an integral part of the nurse's role. METHODS: Guided by Whittemore
& Knafl's five-stage framework, primary peer-reviewed studies published in
English between 2000 and 2018 were searched using CINAHL, PubMed, ProQuest,
PsycINFO and Scopus. The initial search yielded 292 papers. Twenty-seven papers
were included in this review: quantitative (n = 18), qualitative (n = 5) and
mixed-methods (n = 4). RESULTS: Findings showed that nurses internationally have
poor knowledge and attitudes of basic pain assessment and management principles.
Barriers to effective pain management include the absence of pain education and
assessment tools, parents' reluctance to report pain and insufficient
prescription of analgesia by physicians. Facilitators for the effective
management of pain include parental participation in care, trusting and
respectful relationships between nurses and children, and adequate nurse-patient
ratios. CONCLUSION: The review findings suggest a need to improve education for
nurses, doctors and the patients' family in relation to paediatric pain
management, communication and interprofessional collaborations. There is a need
to maximize facilitators and overcome barriers, such as those identified in this
review, to ensure the quality of paediatric pain management. IMPLICATIONS FOR
NURSING AND HEALTH POLICY: Nursing and health policy should mandate the
prioritization of paediatric pain management and the clinical roles and
responsibilities of the interdisciplinary team members. Undergraduate,
postgraduate and in-service education for nurses and other health professionals
should also address paediatric pain management. In-service education on
paediatric pain management should be compulsory for all health professionals
caring for children.
PMID- 29956311
TI - The pink salmon invasion: a Norwegian perspective.
PMID- 29956312
TI - Oust the louse: leaping behaviour removes sea lice from wild juvenile sockeye
salmon Oncorhynchus nerka.
AB - We conducted a manipulative field experiment to determine whether the leaping
behaviour of wild juvenile sockeye salmon Oncorhynchus nerka dislodges
ectoparasitic sea lice Caligus clemensi and Lepeophtheirus salmonis by comparing
sea-lice abundances between O. nerka juveniles prevented from leaping and
juveniles allowed to leap at a natural frequency. Juvenile O. nerka allowed to
leap had consistently fewer sea lice after the experiment than fish that were
prevented from leaping. Combined with past research, these results imply
potential costs due to parasitism and indicate that the leaping behaviour of
juvenile O. nerka does, in fact, dislodge sea lice.
PMID- 29956313
TI - Parasite communities of the white seabream Diplodus sargus sargus in the marine
protected area of Medes Islands, north-west Mediterranean Sea.
AB - Marine protected areas are considered a useful tool to preserve and recover the
biodiversity of ecosystems. It is suggested that fisheries not only affect
populations of target and bycatch species but also their parasite communities.
Parasites can indicate fishery effects on host species and also on the whole
local community, but the effects of fisheries and protection measures on parasite
communities are relatively unknown. This study analyses parasite communities of
the white seabream Diplodus sargus sargus in order to assess potential effects
exerted by protection measures within and by fisheries outside a reserve in the
western Mediterranean Sea. This small scale analysis offered the opportunity to
study different degrees of fishery effects on parasite infracommunities, without
considering climatic effects as an additional factor. Parasite infracommunities
of fishes from the no-take zone (NTZ) differed in their composition and structure
compared with areas completely or partially open to fisheries. The detected
spatial differences in the infracommunities derived from generalist parasites and
varied slightly between transmission strategies. Monoxenous parasites were richer
and more diverse in both fished areas, but more abundant in the no-take, whereas
richness and abundance of heteroxenous parasites were higher for the NTZ. In
addition to host body size as one factor explaining these spatial variations,
differences within parasite infracommunities between the areas may also be linked
to increased host densities and habitat quality since the implementation of the
NTZ and its protection measures.
PMID- 29956314
TI - Is psoriasis a risk factor of angiography-proven coronary artery disease?
PMID- 29956315
TI - The beach-spawning California grunion Leuresthes tenuis eats and digests
conspecific eggs.
AB - Apparent egg cannibalism was investigated in the beach-spawning California
grunion Leuresthes tenuis. Three hypotheses were tested to determine whether L.
tenuis regularly consumes and efficiently digests conspecific eggs. First,
examination of the gut contents of adults collected at four spawning sites over
two seasons showed that the intestines of most fish from all the sites (57-87%, n
>= 30, each site) contained L. tenuis eggs. The two other hypotheses focused on
digestion of the eggs. First, the force required to crush cannibalized eggs was
significantly less than that for uncannibalized eggs (fertilized or
unfertilized), indicating that ingestion weakens the egg chorions. Second,
conspecific eggs fed to fish held in the laboratory visibly degraded as they
passed through the gut. The eggs lost c. half of their protein content and about
two-thirds of their lipid content as they passed from proximal to distal regions
of the gut, indicating that digestion occurred. Digestive enzyme activities of
the gut further confirmed that L. tenuis can break down the contents of ingested
eggs. Trypsin activity decreased and aminopeptidase activity increased
posteriorly along the gut, whereas amylase and lipase activities exhibited less
clear patterns by gut region. As far as is known, this study is the first to show
that L. tenuis is an egg cannibal.
PMID- 29956316
TI - Effects of elevated temperature on osmoregulation and stress responses in
Atlantic salmon Salmo salar smolts in fresh water and seawater.
AB - Smolting in Atlantic salmon Salmo salar is a critical life-history stage that is
preparatory for downstream migration and entry to seawater that is regulated by
abiotic variables including photoperiod and temperature. The present study was
undertaken to determine the interaction of temperature and salinity on salinity
tolerance, gill osmoregulatory proteins and cellular and endocrine stress in S.
salar smolts. Fish were exposed to rapid changes in temperature (from 14 to 17,
20 and 24 degrees C) in fresh water (FW) and seawater (SW), with and without
prior acclimation and sampled after 2 and 8 days. Fish exposed simultaneously to
SW and 24 degrees C experienced 100% mortality, whereas no mortality occurred in
any of the other groups. The highest temperature also resulted in poor ion
regulation in SW with or without prior SW acclimation, whereas no substantial
effect was observed in FW. Gill Na+ -K+ -ATPase (NKA) activity increased in SW
fish compared to FW fish and decreased with high temperature in both FW and SW.
Gill Nkaalpha1a abundance was high in FW and Nkaalpha1b and Na+ -K+ -2Cl-
cotransporter high in SW, but all three were lower at the highest temperature.
Gill Hsp70 levels were elevated in FW and SW at the highest temperature and
increased with increasing temperature 2 days following direct transfer to SW.
Plasma cortisol levels were elevated in SW at the highest temperature. Our
results indicate that there is an important interaction of salinity and elevated
temperature on osmoregulatory performance and the cellular stress response in S.
salar, with an apparent threshold for osmoregulatory failure in SW above 20
degrees C.
PMID- 29956317
TI - Genetic population structure of the convict surgeonfish Acanthurus triostegus: a
phylogeographic reassessment across its range.
AB - This study investigates the genetic population structure and connectivity of
Acanthurus triostegus in five Indo-Pacific biogeographic regions (western and
eastern Indian Ocean, western, central and eastern Pacific Ocean), using a
mitochondrial DNA marker spanning the ATPase8 and ATPase6 gene regions. In order
to assess the phylogeography and genetic population structure of A. triostegus
across its range, 35 individuals were sampled from five localities in the western
Indian Ocean and complemented with 227 sequences from two previous studies.
Results from the overall analysis of molecular variance (AMOVA) without a priori
grouping showed evidence of significant differentiation in the Indo-Pacific, with
25 (8.3%) out of 300 pairwise PhiST comparisons being significant. However, the
hierarchical AMOVA grouping of Indian and Pacific Ocean populations failed to
support the vicariance hypothesis, showing a lack of a genetic break between the
two ocean basins. Instead, the correlation between pairwise PhiST values and
geographic distance showed that dispersal of A. triostegus in the Indo-Pacific
Ocean follows an isolation-by-distance model. Three haplogroups could be deduced
from the haplotype network and phylogenetic tree, with haplogroup 1 and 2
dominating the Indian and the Pacific Ocean, respectively, while haplogroup 3
exclusively occurring in the Hawaiian Archipelago of the central Pacific Ocean.
PMID- 29956318
TI - A comparison of two techniques for induction of anaesthesia with target
controlled infusion of propofol.
AB - Induction of anaesthesia with target-controlled infusion of propofol may be
achieved by stepwise increases in effect-site concentration until the patient
loses consciousness (titration method), or by setting a high effect-site
concentration target and observing the calculated effect-site concentration at
loss of consciousness (standard method). When the estimated effect-site
concentration at loss of consciousness is accurate, the difference between effect
site concentration at loss of consciousness and at recovery of consciousness
should be small. This prospective, randomised, controlled trial was designed to
compare this difference (effect-site concentration at loss of consciousness -
effect-site concentration at recovery of consciousness) associated with the two
techniques. Sixty-seven healthy patients undergoing elective hemithyroidectomy
were recruited. Induction of anaesthesia was achieved using effect-site target
controlled infusion with the modified Marsh model and ke0 of 1.2 min-1 . The
median (IQR [range]) difference between effect-site concentration at loss of
consciousness and recovery of consciousness was significantly lower in patients
in the titration group at 1.2 (0.8-1.5 [0.1-2.9]) MUg.ml-1 compared with the
standard group 2.1 (1.9-2.6 [0.2-3.6] MUg.ml-1 ; p < 0.0001). There was a
positive correlation between effect-site concentration at loss of, and recovery
of, consciousness (R = 0.41, p = 0.016) in the titration group, which was not
seen in the standard group (R = -0.15, p = 0.44). In conclusion, using the
modified Marsh pharmacokinetic model, the titration method for target-controlled
infusion propofol at induction of anaesthesia allows closer matching of propofol
concentration to depth of anaesthesia than the standard method.
PMID- 29956319
TI - Molecular diet analysis reveals predator-prey community dynamics and
environmental factors affecting predation of larval lake sturgeon Acipenser
fulvescens in a natural system.
AB - This study utilized molecular tools to quantify the prevalence of predation
during the vulnerable drifting larval life-history stage of lake sturgeon
Acipenser fulvescens. How predators, the co-distributed prey community and
abiotic environmental conditions (e.g., stream substrata) affected predation
levels was quantified. Nightly D-frame drift net surveys were used to estimate
the biomass of A. fulvescens and co-distributed prey. Gastrointestinal diet
samples (n = 1,140) from 28 species of potential fish predators were collected
during electrofishing surveys. Sampling was conducted for 17 days across 2015 and
2016. Based on DNA barcode analysis using sturgeon-specific mtDNA cytochrome
oxidase I primers, A. fulvescens DNA was detected in 73 of 1,140 diet samples
(6.40%) from 16 of the 28 predator species examined. A logistic regression model
was used to analyse the effects of biotic and abiotic variables associated with
the likelihood a predator had consumed larval A. fulvescens. Increasing lunar
illumination and biomass of larval A. fulvescens increased predation rates on
larval A. fulvescens. Higher discharge and greater biomass and proportions of
alternative prey decreased predation rates of larval A. fulvescens. Predation
rates were slightly higher in habitats with sand substrata. Most predator species
preyed upon larval A. fulvescens at similar rates. The study revealed
considerably higher incidence of predation on larval A. fulvescens than previous
studies had documented using traditional morphological diet analysis. Co
distributed prey and abiotic environmental variables that affected the predation
rates of a species of regional conservation concern can inform future management
actions.
PMID- 29956320
TI - Power mobility for children: a survey study of American and Canadian therapists'
perspectives and practices.
AB - AIM: To explore the views and practices of paediatric occupational therapists and
physical therapists in Canada and the USA regarding the implementation of power
mobility for children with mobility limitations. METHOD: This descriptive study
utilized a web-based survey that included questions pertaining to therapists'
decisions to trial and use power mobility, agreement or disagreement with
statements developed from published practice considerations regarding power
mobility, and the frequency of performing tasks related to power mobility
prescription and training. RESULTS: Most respondents reported that child
characteristics (e.g. cognition, safety awareness) were important factors in
decision-making about power mobility, whereas other child characteristics (e.g.
communication abilities, age) were not as important. Family resources and home
accessibility were also not considered important. The average age at which
respondents considered power mobility for children was 2 years 3 months. The
majority of respondents agreed with statements developed from published practice
considerations and most frequently performed various power mobility tasks twice a
year or less. INTERPRETATION: Although most respondents appeared to have positive
views regarding power mobility, few appeared to actively perform power mobility
tasks in their practice. Resources to support therapists in the early
introduction of power mobility may be beneficial. WHAT THIS PAPER ADDS:
Occupational and physical therapists positively view early introduction of power
mobility for children with mobility limitations. Few therapists actively provide
early power mobility experiences. Power mobility training and monitoring power
mobility devices are important therapist roles.
PMID- 29956322
TI - Aerial and aquatic visual acuity of the grey bichir Polypterus senegalus, as
estimated by optokinetic response.
AB - The present study assessed the aerial and aquatic visual abilities of juvenile
grey bichir Polypterus senegalus, fish capable of terrestrial locomotion, by
measuring the optokinetic response to stimuli of varying speed and spatial
frequency. In water, fish tracked slow-moving (2 degrees s-1 ) stimuli
moderately well and fast-moving stimuli very poorly. Spatial acuity was very low
compared with many other species, with maximum response observed at 0.05-0.075
stimulus cycles per degree of visual arc; however, it should be noted that adult
fish, with their larger eyes, are likely to have somewhat improved spatial
acuity. Low spatial acuity and limited stimulus tracking ability might be
expected in a nocturnal ambush predator such as P. senegalus, where gaze
stabilization may be less crucial and other sensory inputs may have greater
importance in perception of the environment. In air, spatial and temporal acuity
were both poorer by every measure, but some visual ability persisted. As the eye
shows no anatomical specialization for aerial vision, poor vision was expected;
however, the large decrease in saccade velocity observed in air trials was
unexpected. Stimulus parameters typically have little effect on the
characteristics of the saccade, so this finding may suggest that the function of
the reflex system itself could be compromised in the aerial vision of some fishes
capable of terrestrial locomotion.
PMID- 29956321
TI - Spawning-stock characteristics and migration of a lake-bound population of the
endangered Macquarie perch Macquaria australasica.
AB - The intrapopulation variability in the size and age structure of the spawning
stock and migration of the threatened Macquarie perch Macquaria australasica in
Lake Dartmouth was investigated between 2008 and 2016. Sampling centred on the
core reproductive period (October-December) when mature fish migrate from the
lake into riverine habitat to spawn. Spawning fish were predominantly large,
spanning a broad age structure, with a high proportion of fish (25%) aged 15-30
years. The overall median size of spawning fish did not change for males or
females during the 9 year study period. The size of the smaller mature male fish
did change in some years suggesting a small proportion of male M. australasica
matured at age 1+ and 2+. Acoustic telemetry employed over 3 years showed that M.
australasica were most likely to be in the spawning reach from October to mid
December, migrated to this reach annually and moved large distances throughout
the lake all year, with no evidence for any spatial structuring. Mature fish
sometimes occupied the spawning reach for several months after the core
reproductive period, which increased their vulnerability to recreational fishing.
Males tagged in the lake were seldom recorded in the spawning reach, presumably
because a high proportion had not yet entered the spawning stock despite their
size suggesting maturity. Maintaining a broad age and size-structure of the
spawning stock of long-lived iteroparous fish species is crucial for recruitment
stability and population persistence. Overexploitation of the spawning stock has
probably contributed to previous population declines in the lake as well as the
collapse of other M. australasica populations in south-eastern Australia.
PMID- 29956323
TI - Characterization, tissue distribution of apela and periprandial, fasting and
refeeding changes of apela mRNA in Siberian sturgeon Acipenser baerii.
AB - Apela identified from zebrafish Danio rerio for the first time in 2013 is a novel
endogenous peptide ligand for the apelin receptor. To study the role of apela in
regulating fish feeding, the complementary (c) DNA sequence of apela of Siberian
sturgeon Acipenser baerii was cloned for the first time. The apela cDNA fragment
of 836 bp was obtained by cloning. The open reading frame (ORF) of apela was 165
bp encoding a 54 amino acid, including 22 amino acids signal peptide and two
proteolytic sites. Phylogenetic tree analysis showed that A. baerii apela was
clustered with mammalian and amphibian sequences. A. baerii apela messeger (m)RNA
was widely distributed in 11 tissues related to feeding, with high expressions in
brain, oesophagus and stomach, especially in the brain. The level of apela mRNA
in brain increased significantly after feeding. On the first day of fasting,
apela expression in brain was significantly lower than that of the fed group, but
after fasting for 3-15 days, the expression of apela in A. baerii brain was
significantly higher than that in the fed group. After refeeding apela mRNA
expression was obviously reduced. These results suggest that apela plays a
bidirectional role in feeding regulation of A. baerii, which may serve as a short
term satiation factor and a long-term hunger factor.
PMID- 29956325
TI - Reproductive biology of the tiger pleco Panaqolus tankei (Loricariidae) in a
lentic system of the Amazon Basin.
AB - This study presents the first information on the reproduction of the recently
described tiger pleco Panaqolus tankei, from Lake Bolonha in the north-eastern
Amazon Basin. This loricariid has a long reproductive period, fractionated
spawning and low fecundity (on average, female gonads contained 37 oocytes), a
total length (LT ) at first maturity of 47.4 mm for females and 54.1 mm LT for
males. Correlation of the condition factor and gonado-somatic index with
environmental variables suggests that turbidity favours P. tankei reproduction in
this environment.
PMID- 29956324
TI - The choroid plexus sodium-bicarbonate cotransporter NBCe2 regulates mouse
cerebrospinal fluid pH.
AB - KEY POINTS: Normal pH is crucial for proper functioning of the brain, and
disorders increasing the level of CO2 in the blood lead to a decrease in brain
pH. CO2 can easily cross the barriers of the brain and will activate
chemoreceptors leading to an increased exhalation of CO2 . The low pH, however,
is harmful and bases such as HCO3 - are imported across the brain barriers in
order to normalize brain pH. We show that the HCO3 - transporter NBCe2 in the
choroid plexus of the blood-cerebrospinal fluid barrier is absolutely necessary
for normalizing CSF pH during high levels of CO2 . This discovery represents a
significant step in understanding the molecular mechanisms behind regulation of
CSF pH during acid-base disturbances, such as chronic lung disease. ABSTRACT: The
choroid plexus epithelium (CPE) is located in the brain ventricles where it
produces the majority of the cerebrospinal fluid (CSF). The hypothesis that
normal brain function is sustained by CPE-mediated CSF pH regulation by extrusion
of acid-base equivalents was tested by determining the contribution of the
electrogenic Na+ -HCO3 - cotransporter NBCe2 to CSF pH regulation. A novel strain
of NBCe2 (Slc4a5) knockout (KO) mice was generated and validated. The base
extrusion rate after intracellular alkalization was reduced by 77% in NBCe2 KO
mouse CPE cells compared to control mice. NBCe2 KO mice and mice with CPE
targeted NBCe2 siRNA knockdown displayed a reduction in CSF pH recovery during
hypercapnia-induced acidosis of approximately 85% and 90%, respectively, compared
to control mice. NBCe2 KO did not affect baseline respiration rate or tidal
volume, and the NBCe2 KO and wild-type (WT) mice displayed similar ventilatory
responses to 5% CO2 exposure. NBCe2 KO mice were not protected against
pharmacological or heating-induced seizure development. In conclusion, we
establish the concept that the CPE is involved in the regulation of CSF pH by
demonstrating that NBCe2 is necessary for proper CSF pH recovery after
hypercapnia-induced acidosis.
PMID- 29956327
TI - Decoding the gene coexpression network underlying the ability of Gevuina avellana
to live in diverse light conditions.
AB - Gevuina avellana (Proteaceae) is a typical tree from the South American temperate
rainforest. Although this species mostly regenerates in shaded understories, it
exhibits an exceptional ecological breadth, being able to live under a wide range
of light conditions. Here we studied the genetic basis that underlies
physiological acclimation of the photosynthetic responses of G. avellana under
contrasting light conditions. We analyzed carbon assimilation and light energy
used for photochemical processes in plants acclimated to contrasting light
conditions. Also, we used a transcriptional profile of leaf primordia from G.
avellana saplings growing under different light environments in their natural
habitat, to identify the gene coexpression network underpinning photosynthetic
performance and light-related processes. The photosynthetic parameters revealed
optimal performance regardless of light conditions. Strikingly, the mechanism
involved in dissipation of excess light energy showed no significant differences
between high- and low-light-acclimated plants. The gene coexpression network
defined a community structure consistent with the photochemical responses,
including genes involved mainly in assembly and functioning of photosystems,
photoprotection, and retrograde signaling. This ecophysiological genomics
approach improves our understanding of the intraspecific variability that allows
G. avellana to have optimal photochemical and photoprotective mechanisms in the
diverse light habitats it encounters in nature.
PMID- 29956326
TI - Psychopharmacological effects and safety of styryl-2-pyrones and dihydrostyryl-2
pyrones-rich fraction from Polygala sabulosa: absence of withdrawal syndrome and
tolerance to anxiolytic-like and anticonvulsant effects.
AB - OBJECTIVES: To investigate whether mice develop tolerance to the anxiolytic-like
and anticonvulsant effects of subchronic treatment with EA (the styryl-2-pyrones
and dihydrostyryl-2-pyrones-rich fraction of Polygala sabulosa), as well as any
withdrawal symptoms after abrupt discontinuation; to compare the effects of EA
with those of diazepam (DZP) on withdrawal-induced anxiety; and to evaluate the
toxicity of EA according to OECD guidelines. METHODS: Male or female mice were
acutely or subchronically treated with EA or DZP, and their tolerance to
anxiolytic (evaluated in the elevated plus maze, EPM) and anticonvulsant effects
(measured against pentylenetetrazole (PTZ)-induced convulsions) were
investigated. Other groups received EA or DZP for 28 days followed by withdrawal,
being the anxiety-like behaviour evaluated in the EPM. KEY FINDINGS: Both acute
and subchronic treatments with EA induced an anxiolytic effect in the EPM. The
anticonvulsant activity of DZP, but not EA, was reduced by protracted treatment.
EA withdrawal retained the anxiolytic profile, while DZP withdrawal induced
anxiogenesis. EA counteracted the anxiogenic-like actions of DZP withdrawal. EA
has low toxicity as it did not cause any changes in the biochemical,
haematological and histopathological markers. CONCLUSIONS: EA avoids the
development of tolerance to its anxiolytic-like and anticonvulsant actions, and
does not promote withdrawal syndrome. EA does not cause relevant toxic effects in
rodents.
PMID- 29956328
TI - A novel formulation of zolpidem for direct nose-to-brain delivery: synthesis,
encapsulation and intranasal administration to mice.
AB - OBJECTIVES: Anxiolytic drug zolpidem was incorporated into the microcontainers
based on mesoporous calcium carbonate particles modified by diethylaminoethyl
dextran/hyaluronic acid shell. The release of zolpidem in saline solution and in
polymer film modelling nasal mucosa was investigated. The anxiolytic effect of
zolpidem upon intranasal administration of microcontainers and free medicine was
determined by in vivo experiments on mice. METHODS: The structures of all
compounds during zolpidem synthesis were established using nuclear magnetic
resonance spectroscopy. The loading efficacy and release kinetics of zolpidem
were analysed by spectrophotometry. Surface morphology of formulation was
investigated by scanning electron microscopy. To determine the effect of zolpidem
loaded containers administration by the intranasal route in vivo experiments was
carried out applying the open field test. KEY FINDINGS: Nasal administration of
zolpidem in the form of the microcontainers based on mesoporous calcium carbonate
particles modified by diethylaminoethyl-dextran/hyaluronic acid shell has a
pronounced anxiolytic effect on the behaviour of the animals in the open field
test. CONCLUSIONS: The polyelectrolyte shell deposited together with zolpidem
enhances the loading efficacy of the microcontainers. In vivo experiments on mice
demonstrate increase in anxiolytic effect of zolpidem in microcontainers compared
with upon intranasal administration of free medicine.
PMID- 29956329
TI - Reconsidering pectoral girdle and fin morphology in Anguillidae (Elopomorpha:
Anguilliformes).
AB - The morphology of the pectoral girdle and fin of Anguillidae is reconsidered via
the inclusion of skeletal components that have previously been unassessed. For
example, the pectoral girdle and fin in Anguilla were erroneously reported to
lack a scapular bone, a cartilaginous scapulocoracoid plate and a cartilaginous
propterygium. The pectoral morphology of Anguilla is also compared with the
closely related genus Nemichthys, including additional data on the anatomy of
this eel family.
PMID- 29956330
TI - Food for thought: formulating away the food effect - a PEARRL review.
AB - OBJECTIVES: Co-ingestion of oral dosage forms with meals can cause substantial
changes in bioavailability relative to the fasted state. Food-mediated effects on
bioavailability can have significant consequences in drug development, regulatory
and clinical settings. To date, the primary focus of research has focused on the
ability to mechanistically understand the causes and predict the occurrence of
these effects. KEY FINDINGS: The current review describes the mechanisms
underpinning the occurrence of food effects, sheds new insights on the relative
frequency for newly licensed medicines and describes the various methods by which
they can be overcome. Analysis of oral medicines licensed by either the EMA or
FDA since 2010 revealed that over 40% display significant food effects. Due to
altered bioavailability, these medicines are often required to be dosed, rather
restrictively, in either the fed or the fasted state, which can hinder clinical
usefulness. SUMMARY: There are clinical and commercial advantages to predicting
the presence of food effects early in the drug development process, in order to
mitigate this risk of variable food effect bioavailability. Formulation
approaches aimed at reducing variable food-dependent bioavailability, through the
use of bio-enabling formulations, are an essential tool in addressing this
challenge and the latest state of the art in this field are summarised here.
PMID- 29956331
TI - Antifungal mechanism of action of Schinus lentiscifolius Marchand essential oil
and its synergistic effect in vitro with terbinafine and ciclopirox against
dermatophytes.
AB - OBJECTIVES: The aim of this study was to evaluate the antifungal, antichemotactic
and antioxidant activities of Schinus lentiscifolius essential oil, as well as
its combined effect with terbinafine and ciclopirox, against dermatophytes.
METHODS: Essential oil was analysed by GC-MS. The antifungal activity and the
mechanism of action were determined by broth microdilution, sorbitol and
ergosterol assays, as well as scanning electron microscopy. The checkerboard
method was used for evaluating the interactions with commercial antifungal
agents. The antioxidant and antichemotactic activities were measured using the
DPPH and the modified Boyden chamber methods, respectively. KEY FINDINGS:
Chemical analysis revealed the presence of 33 compounds, the primary ones being
gamma-eudesmol (12.8%) and elemol (10.5%). The oil exhibited 97.4% of
antichemotactic activity and 37.9% of antioxidant activity. Antifungal screening
showed effect against dermatophytes with minimum inhibitory concentration values
of 125 and 250 MUg/ml. Regarding the mechanisms of action, the assays showed that
the oil can act on the fungal cell wall and membrane. Synergistic interactions
were observed using the combination with antifungals, primarily terbinafine.
CONCLUSIONS: Schinus lentiscifolius essential oil acted as a chemosensitizer of
the fungal cell to the drug, resulting in an improvement in the antifungal
effect. Therefore, this combination can be considered as an alternative for the
topical treatment of dermatophytosis.
PMID- 29956332
TI - Revealing mechanisms of salinity tissue tolerance in succulent halophytes: A case
study for Carpobrotus rossi.
AB - Efforts to breed salt tolerant crops could benefit from investigating previously
unexplored traits. One of them is a tissue succulency. In this work, we have
undertaken an electrophysiological and biochemical comparison of properties of
mesophyll and storage parenchyma leaf tissues of a succulent halophyte species
Carpobrotus rosii ("pigface"). We show that storage parenchyma cells of C. rossii
act as Na+ sink and possessed both higher Na+ sequestration (298 vs. 215 mM NaCl
in mesophyll) and better K+ retention ability. The latter traits was determined
by the higher rate of H+ -ATPase operation and higher nonenzymatic antioxidant
activity in this tissue. Na+ uptake in both tissues was insensitive to either
Gd3+ or elevated Ca2+ ruling out involvement of nonselective cation channels as a
major path for Na+ entry. Patch-clamp experiments have revealed that Caprobrotus
plants were capable to downregulate activity of fast vacuolar channels when
exposed to saline environment; this ability was higher in the storage parenchyma
cells compared with mesophyll. Also, storage parenchyma cells have constitutively
lower number of open slow vacuolar channels, whereas in mesophyll, this
suppression was inducible by salt. Taken together, these results provide a
mechanistic basis for efficient Na+ sequestration in the succulent leaf tissues.
PMID- 29956333
TI - The southernmost records of Brotula barbata (Bloch & Schneider 1801)
(Ophidiiformes: Ophidiidae) in the western Atlantic Ocean.
AB - The present study reports the occurrence of the bearded brotula, Brotula barbata,
in four different localities off southern Brazil. These records extend the
species' known distribution limit southwards, beyond Rio de Janeiro, to the state
of Rio Grande do Sul (30 degrees 50' S). Morphometric and meristic data for the
specimens reported herein are provided and discussed.
PMID- 29956334
TI - Internal breast dosimetry in mammography: Monte Carlo validation in homogeneous
and anthropomorphic breast phantoms with a clinical mammography system.
AB - PURPOSE: To validate Monte Carlo (MC)-based breast dosimetry estimations using
both a homogeneous and a 3D anthropomorphic breast phantom under polyenergetic
irradiation for internal breast dosimetry purposes. METHODS: Experimental
measurements were performed with a clinical digital mammography system (Mammomat
Inspiration, Siemens Healthcare), using the x-ray spectrum selected by the
automatic exposure control and a tube current-exposure time product of 360 mAs. A
homogeneous 50% glandular breast phantom and a 3D anthropomorphic breast phantom
were used to investigate the dose at different depths (range 0-4 cm with 1 cm
steps) for the homogeneous case and at a depth of 2.25 cm for the anthropomorphic
case. Local dose deposition was measured using thermoluminescent dosimeters
(TLD), metal oxide semiconductor field-effect transistor dosimeters (MOSFET), and
GafChromicTM films. A Geant4-based MC simulation was modified to match the
clinical experimental setup. Thirty sensitive volumes (3.2 * 3.2 * 0.38 mm3 ) on
the axial-phantom plane were included at each depth in the simulation to
characterize the internal dose variation and compare it to the experimental TLD
and MOSFET measurements. The experimental 2D dose maps obtained with the
GafChromicTM films were compared to the simulated 2D dose distributions. RESULTS:
Due to the energy dependence of the dosimeters and due to x-ray beam hardening,
dosimeters based on these three technologies have to be calibrated at each depth
of the phantom. As expected, the dose was found to decrease with increasing
phantom depth, with the reduction being ~93% after 4 cm for the homogeneous
breast phantom. The 2D dose map showed nonuniformities in the dose distribution
in the axial plane of the phantom. The mean combined standard uncertainty
increased with phantom depth by up to 5.3% for TLD, 6.3% for MOSFET, and 9.6% for
GafChromicTM film. In the case of a heterogeneous phantom, the dosimeters are
able to detect local dose gradient variations. In particular, GafChromicTM film
showed local dose variations of about 46% at the boundaries of two materials.
CONCLUSIONS: Results showed a good agreement between experimental measurements
(with TLD and MOSFET) and MC data for both homogeneous and anthropomorphic breast
phantoms. Larger discrepancies are found when comparing the GafChromicTM dose
values to the MC results due to the inherent less precise nature of the former.
MC validations in a heterogeneous background at the level of local dose
deposition and in absolute terms play a fundamental role in the development of an
accurate method to estimate radiation dose. The potential introduction of a
breast dosimetry model involving a nonhomogeneous glandular/adipose tissue
composition makes the validation of internal dose distributions estimates
crucial.
PMID- 29956335
TI - Toward in vivo dosimetry in external beam radiotherapy using x-ray acoustic
computed tomography: A soft-tissue phantom study validation.
AB - PURPOSE: To study, using phantoms made from biological tissues, the feasibility
and practical challenges of monitoring the position of the radiation beam and the
deposited dose by x-ray acoustic computed tomography (XACT) during external beam
radiotherapy delivery. MATERIAL AND METHODS: A prototype XACT system with a
single immersion ultrasound transducer, which was positioned around the target
sample driven by a motor-controlled rotation stage, was used to acquire the x-ray
acoustic (XA) signals produced by a medical linear accelerator (Linac) to form an
XACT image of the irradiated phantom. To investigate the feasibility of XACT in
tracking the position of radiation dose, a large piece of veal liver with
embedded fat tissue was imaged and beam misalignments were measured. Next, we
explored the sensitivity of XACT in monitoring and quantifying the delivered
dose, in which a block of porcine gel was embedded with equally spaced lard
cylinders and imaged. The doses on the lard cylinders modulated by physical
wedges were quantified from the XACT image and were verified by comparison to
measurements from radiochromic films as the gold standard. Then, to simulate how
XACT can perform in a targeted tissue in the human body, a porcine gel phantom
with lard cylinders covered by different materials (bone, muscle, and air gap,
respectively) was also imaged. RESULTS: The reconstructed XACT images of the
phantoms show congruence with the boundaries of the beam field and the interfaces
between the different tissue materials. The beam displacement from the target was
tracked properly by the reconstructed XACT images. An intensity difference as
small as 2.9% in delivered dose region can be measured from XACT images P = 0.02.
The intensities of XACT images were highly correlated to the film measurements
with an R2 better than 0.986. The expected variances of dose delivered to
different target regions as a result of the difference in attenuation were
successfully captured by the XACT images. CONCLUSIONS: This study validated the
feasibility of XACT in accurately obtaining relative dose maps of tissue
mimicking phantoms. XACT offers a practical method for verifying the beam
position against the target and quantifying the relative dose delivered to the
target during external beam radiotherapy.
PMID- 29956336
TI - From plant cell wall metabolism and plasticity to cell wall biotechnology.
PMID- 29956337
TI - 'Saying no to organ donation': an empirical typology of reluctance and rejection.
AB - In Germany, as well as in other countries, organ shortages are usually explained
by a relative unwillingness to donate among a population which is assumed to be
caused by a lack of information and mistrust of the system. As we can see in the
data of our qualitative research (focus groups and interviews), lack of
information or mistrust are not the only reasons for people to be reluctant to
agree to the donation of their organs after death. In fact we can identify four
positions: (1) information deficit; (2) mistrust; (3) no killing; and (4) bodily
integrity. The first and second are the two prominent explanations in the public
discourse about low donation rates. The third and the fourth instead have neither
been adequately articulated nor been discussed as a proper argument. Therefore,
by means of sociology of critique, we discuss their contribution to the discourse
as comprehensible reasons for reluctance and present them as credible positions
of criticism: These two positions illuminate fundamental and universal values of
the inviolability of the person and human dignity. Thus, both positions are
consistent and morally justifiable and should be addressed with sensitivity.
PMID- 29956338
TI - In vitro methods to assess drug precipitation in the fasted small intestine - a
PEARRL review.
AB - OBJECTIVES: Drug precipitation in vivo poses a significant challenge for the
pharmaceutical industry. During the drug development process, the impact of drug
supersaturation or precipitation on the in vivo behaviour of drug products is
evaluated with in vitro techniques. This review focuses on the small and full
scale in vitro methods to assess drug precipitation in the fasted small
intestine. KEY FINDINGS: Many methods have been developed in an attempt to
evaluate drug precipitation in the fasted state, with varying degrees of
complexity and scale. In early stages of drug development, when drug quantities
are typically limited, small-scale tests facilitate an early evaluation of the
potential precipitation risk in vivo and allow rapid screening of prototype
formulations. At later stages of formulation development, full-scale methods are
necessary to predict the behaviour of formulations at clinically relevant doses.
Multicompartment models allow the evaluation of drug precipitation after transfer
from stomach to the upper small intestine. Optimisation of available
biopharmaceutics tools for evaluating precipitation in the fasted small intestine
is crucial for accelerating the development of novel breakthrough medicines and
reducing the development costs. SUMMARY: Despite the progress from compendial
quality control dissolution methods, further work is required to validate the
usefulness of proposed setups and to increase their biorelevance, particularly in
simulating the absorption of drug along the intestinal lumen. Coupling results
from in vitro testing with physiologically based pharmacokinetic modelling holds
significant promise and requires further evaluation.
PMID- 29956339
TI - 'Who does this patient belong to?' boundary work and the re/making of (NSTEMI)
heart attack patients.
AB - This ethnography within ten English and Welsh hospitals explores the significance
of boundary work and the impacts of this work on the quality of care experienced
by heart attack patients who have suspected non-ST segment elevation myocardial
infarction (NSTEMI) /non-ST elevation acute coronary syndrome. Beginning with the
initial identification and prioritisation of patients, boundary work informed
negotiations over responsibility for patients, their transfer and admission to
different wards, and their access to specific domains in order to receive
diagnostic tests and treatment. In order to navigate boundaries successfully and
for their clinical needs to be more easily recognised by staff, a patient needed
to become a stable boundary object. Ongoing uncertainty in fixing their clinical
classification, was a key reason why many NSTEMI patients faltered as boundary
objects. Viewing NSTEMI patients as boundary objects helps to articulate the
critical and ongoing process of classification and categorisation in the creation
and maintenance of boundary objects. We show the essential, but hidden, role of
boundary actors in making and re-making patients into boundary objects. Physical
location was critical and the parallel processes of exclusion and restriction of
boundary object status can lead to marginalisation of some patients and
inequalities of care (A virtual abstract of this paper can be viewed at:
https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA).
PMID- 29956340
TI - Beyond the reactive-proactive dichotomy: Rage, revenge, reward, and recreational
aggression predict early high school bully and bully/victim status.
AB - The role of reactive and proactive aggression in school bullying perpetration
remains unclear. In this study, we explore the predictive value of an expanded
model of aggression motives based on the Quadripartite Violence Typology (QVT),
which distinguishes between motivational valence (appetitive or aversive) and
recruitment of deliberative self-control to derive four classes of motives: Rage,
Revenge, Reward, and Recreation. With a sample of 1,802 students from grades 7-9,
we assessed aggression motives via self-report, along with self-report of
bullying perpetration and victimization, which were used to assign students into
categories of Pure Bully, Bully/Victim (B/V), Pure Victim, and Uninvolved. Two
structural models were computed to examine the relationship between these four
categories of bullying involvement and aggression motives, using conservative and
liberal bullying cutoffs. As predicted, B/V status was more strongly related to
Rage and Revenge motives. However, B/Vs had higher scores than Pure Bullies for
almost all aggression motives, including Recreation. We discuss the implications
of addressing Revenge and Recreation, as well as Reward and Rage (which map most
clearly to proactive and reactive aggression, respectively) aggression motives,
for bullying prevention and intervention strategies, especially among adolescents
for whom extant bullying prevention strategies may be ineffective or
counterproductive.
PMID- 29956341
TI - The transformative role of interaction rituals within therapeutic communities.
AB - Mental health settings are fraught with emotion as clients address difficult life
experiences and relational patterns. Clients spend a substantial amount of time
together outside of structured therapy, but little is known about how these
moments are potentially therapeutic, especially as sites of emotional change. We
draw on interaction ritual chain theory to explore how negative emotions in
situations outside of formal therapy can be transformed into positive emotions
and facilitate personal change. The research is based upon a narrative
ethnography of two therapeutic communities for individuals with a diagnosis of
personality disorder. Despite the presence of negative transient emotions in
these rituals, clients experienced positive feelings of solidarity and belonging,
and the majority of clients reported increased feelings of confidence and
positive change. Conversely, dynamics between clients showed clients were not
always supportive of one another and at times, could exclude others, resulting in
isolation and alienation. We argue interactions that generate feelings of
inclusion or exclusion over time are a key component in whether clients gain
positive or negative emotional feeling and experience personal change.
PMID- 29956342
TI - The enduring legacy of black lung: environmental health and contested illness in
Appalachia.
AB - Over the past twenty years there has been a deadly resurgence of coal workers'
pneumoconiosis (CWP), commonly known as black lung disease. While increased
prevalence of the disease is alarming, these data only capture cases where CWP
has been officially recognised. We argue that many more cases of the disease are
going unreported. Drawing from contested environmental illness literature, we
examine issues surrounding diagnostic uncertainty and medical surveillance. We
draw from qualitative data on black lung that includes in-depth interviews,
observation and document analysis. Findings indicate ongoing ambiguity and
contestation over diagnosis of the disease, ranging from clinical and legal
debates to concerted efforts to limit official recognition. While health
screenings are currently available to miners, our results indicate low
participation rates based on disincentives for early detection, logistical
problems, and economic fears. Miners fear workplace discrimination and
retaliation for participation in black lung screening programmes. Implications
for public health policy and future research are discussed.
PMID- 29956343
TI - Untargeted UPLC-Q/TOF-MS-based metabolomics and inductively coupled plasma
optical emission spectroscopic analysis reveal differences in the quality of
ginger from two provinces in Zambia.
AB - OBJECTIVES: This study sought to investigate the differences in the quality of
dried ginger samples obtained from two places in Zambia, Lusaka and Copperbelt in
terms of their secondary metabolite differences and heavy metals content.
METHODS: Ten and eight batches of dried ginger obtained, respectively, from
Lusaka and Copperbelt were analysed using untargeted Q/TOF-MS-based metabolomics
and inductively coupled plasma optical emission spectroscopy (ICP-OES). KEY
FINDINGS: The metabolomics approach yielded 11 differential metabolites that
clearly discriminated between the samples from the two locations. Eight were
found to be more abundant in the samples from Lusaka while three were present in
greater amounts in the samples from Copperbelt. The results of the heavy metal
content analysis for four selected elements, Cd, Pb, As and Cu, showed that the
samples from Copperbelt recorded higher levels. However, all samples contained
levels of the toxic metals, Cd and Pb above permissible limits, making them
unwholesome for human consumption. CONCLUSIONS: The outcome of the heavy metal
content analysis led us to speculate that abiotic stress as a result of these
metals experienced by the ginger rhizomes during cultivation could have
contributed to the metabolites abundance differences. Further studies are,
however, recommended to verify this hypothesis.
PMID- 29956344
TI - Body mass index, facial width-to-height ratio, and perceived formidability in
female Ultimate Fighting Championship (UFC) fighters.
AB - Both facial width-to-height ratio (fWHR) and body mass index (BMI) have been
associated with aggressive behavior in women but how they influence perception of
their potential threat remain unclear. Here, we assessed the effects of fWHR and
BMI on perceived formidability from faces of 42 female Ultimate Fighting
Championship (UFC) fighters. In study 1, BMI, but not fWHR, positively predicted
participants' ratings of aggressiveness and fighting ability from facial
photographs. In study 2, both high fWHR and high BMI composite faces were rated
as more aggressive, tougher, and more likely to win a fight than low fWHR and low
BMI composite faces, respectively. Further analyses revealed that the high BMI
composite face was rated as more aggressive and tougher than the high fWHR
composite face. Taken together, these results suggest that compared to fWHR, BMI
may be a more salient cue to women's formidability.
PMID- 29956345
TI - Impacts of variants of uncertain significance on parental perceptions of children
after prenatal chromosome microarray testing.
AB - OBJECTIVE: There are concerns regarding the potential harms in receipt of
prenatal chromosome microarray (CMA) results, particularly variants of uncertain
significance (VUS). We examined the influence that the return of genomic results
had on parental well-being and perceptions of children's development. METHODS:
Parents (n = 138) of 83 children who underwent prenatal chromosomal microarray
testing completed questionnaires assessing perception of children's development,
parent-child attachment, parental mood, parenting competence, martial
satisfaction, satisfaction with the decision to undergo testing, and attitudes
about genetics at age 12 and/or 36 months. Responses were compared between
parents who received normal/likely benign results and VUS results. RESULTS:
Compared to normal/likely benign results, parents who received VUS results rated
their child as less competent on the BITSEA scale at 12 (beta = -1.65, P = .04)
though not 36 months (P = .43). There were no differences in parent mood, marital
satisfaction, or parenting competence. At 36 months, parents in the VUS group
reported less satisfaction with their decision to undergo genetic testing (beta =
1.51, P = .02). CONCLUSION: Chromosome microarray VUS results have limited impact
on parental well-being and perception of children's development. However, the
initial diminished perception of child competency and later dissatisfaction with
genomic testing indicate the need to assist parents in coping with ambiguous
results.
PMID- 29956346
TI - Congenital diaphragmatic hernia has a better prognosis when associated with a
hernia sac.
AB - OBJECTIVE: To evaluate neonatal mortality and morbidity up to 6 months in
neonates with congenital diaphragmatic hernia (CDH) with or without a hernia sac.
METHODS: Seventy-two cases of isolated CDH were included in a retrospective
single-center study between January 2010 and December 2016. Hernia sac was
defined at the time of surgery or at postmortem examination if the neonate died
before surgery. RESULTS: Seventeen newborns (23.6%) had a hernia sac. Survival at
6 months was significantly greater for isolated CDH with a hernia sac: 100%
versus 63.6% (P = .003). High-frequency oscillatory ventilation was used
significantly more in the no hernia sac group (P = .04). At surgery, the need for
patch repair was significantly lower in the hernia sac group: 12% versus 50% (P =
.005). The prenatal observed/expected lung-to-head ratio was significantly higher
in the hernia sac group than in the no hernia sac group: 49.7% versus 38.6% (P <
.05). CONCLUSION: The presence of a hernia sac in CDH is associated with better
outcome, especially survival at 6 months. If the presence of a hernia sac is
recognized as a particular entity, which carries a good prognosis, it is
necessary to be able to diagnose it prenatally, especially in the era of prenatal
fetal surgery.
PMID- 29956347
TI - Echocardiographic predictors of neonatal illness severity in fetuses with
critical left heart obstruction with intact or restrictive atrial septum.
AB - BACKGROUND: Neonates with critical left heart obstruction and intact atrial
septum (IAS) or restrictive atrial septum (RAS) are at risk for hypoxia within
hours of birth and remain a group at high risk for mortality. METHODS: Prenatally
diagnosed fetuses with critical left heart obstruction and IAS or RAS with follow
up from January 1, 2005, to February 14, 2017, were included. Primary outcome was
a composite measure of severe neonatal illness (pH < 7.15, venous pH < 7.10,
bicarbonate < 16 mmol/L, lactic acid > 5 mmol/L, or median oxygen saturation <
60% within 2 hours of birth). RESULTS: Of 68 live born fetuses, 52 (76.5%) had
hypoplastic left heart syndrome, 14 (20.5%) had critical aortic stenosis, and two
(3%) had complex anatomy with mitral stenosis/atresia. There were 27 (39.7%)
fetuses with IAS and 41 (60.3%) with RAS. Severe neonatal illness was present in
36 (52.9%). The strongest discriminators for severe neonatal illness were a
pulmonary vein A:R VTI <= 2.7 (P < 0.001, AUC 0.93) and larger pulmonary vein
diameter (P = 0.025, AUC 0.77). A:R VTI <= 2.7 predicted death or transplant (log
rank P = 0.03). CONCLUSIONS: In neonates with hypoplastic left heart syndrome and
IAS or RAS, A:R VTI <= 2.7 is predictive of severe neonatal instability. This
threshold can help guide resource planning, delivery management, and improve
fetal intervention criteria.
PMID- 29956348
TI - Rare autosomal trisomies: Important and not so rare.
AB - OBJECTIVE: Noninvasive prenatal testing (NIPT) can assess chromosomes other than
13, 18, 21, X and Y. These rare autosomal trisomies (RATs) can adversely affect
pregnancy outcome. METHODS: A prospective study of NIPT using the Illumina
sequencing platform assessing all chromosomes were reported for further
management. RESULTS: There were 28 RATs identified in 23 388 samples (one in
835), the most common being trisomy 7 (n = 6), followed by trisomy 16 (n = 4) and
trisomy 22 (n = 3). Abnormal outcomes occurred in 16 cases: miscarriage (n = 6),
true fetal mosaicism (n = 5), and fetal structural anomaly on ultrasound (n = 5).
Growth restriction was seen in eight cases and correlated with very low-pregnancy
associated plasma protein-A levels. Two of the 17 live born babies had a
structural anomaly, and one had a phenotype similar to mosaic trisomy 16 despite
a normal microarray result. CONCLUSION: Rare autosomal trisomies are not rare and
often associated with poor obstetric outcomes. They should be discussed with the
clinician to guide management. Pregnancy outcomes varied by chromosome being
generally favourable for some (eg, trisomy 7) and poor for others (eg, trisomy
22). In the presence of a RAT, pregnancy-associated plasma protein-A is
predictive of placental dysfunction and fetal growth restriction.
PMID- 29956349
TI - Are high- and low-molecular-weight sensitizing agents associated with different
clinical phenotypes of occupational asthma?
AB - BACKGROUND: High-molecular-weight (HMW) proteins and low-molecular-weight (LMW)
chemicals can cause occupational asthma (OA) although few studies have thoroughly
compared the clinical, physiological, and inflammatory patterns associated with
these different types of agents. The aim of this study was to determine whether
OA induced by HMW and LMW agents shows distinct phenotypic profiles. METHODS:
Clinical and functional characteristics, and markers of airway inflammation were
analyzed in an international, multicenter, retrospective cohort of subjects with
OA ascertained by a positive inhalation challenge response to HMW (n = 544) and
LMW (n = 635) agents. RESULTS: Multivariate logistic regression analysis showed
significant associations between OA caused by HMW agents and work-related
rhinitis (OR [95% CI]: 4.79 [3.28-7.12]), conjunctivitis (2.13 [1.52-2.98]),
atopy (1.49 [1.09-2.05]), and early asthmatic reactions (2.86 [1.98-4.16]). By
contrast, OA due to LMW agents was associated with chest tightness at work (2.22
[1.59-3.03]), daily sputum (1.69 [1.19-2.38]), and late asthmatic reactions (1.52
[1.09-2.08]). Furthermore, OA caused by HMW agents showed a higher risk of
airflow limitation (1.76 [1.07-2.91]), whereas OA due to LMW agents exhibited a
higher risk of severe exacerbations (1.32 [1.01-1.69]). There were no differences
between the two types of agents in the baseline sputum inflammatory profiles, but
OA caused by HMW agents showed higher baseline blood eosinophilia and a greater
postchallenge increase in fractional nitric oxide. CONCLUSION: This large cohort
study describes distinct phenotypic profiles in OA caused by HMW and LMW agents.
There is a need to further explore differences in underlying pathophysiological
pathways and outcome after environmental interventions.
PMID- 29956351
TI - Giant aneurysmal benign fibrous histiocytoma (dermatofibroma).
AB - Aneurysmal benign fibrous histiocytomas are variants of dermatofibromas. These
benign blood-filled lesions can mimic malignancies due to their rapid and
recurrent growth. Our patient is a 42-year-old Caucasian female with a past
medical history of morbid obesity, diabetes, and hypertension, who presented with
a mass on her left shoulder for 5 years' duration. The mass oozed occasionally
and would appear to regress but then recur replaced with progressively larger
masses. Upon inspection, the patient had a large pedunculated exophytic mass with
vascularity. The mass was surgically removed under general anesthesia via wide
local excision. Grossly, the excised skin was purple-tinged with an underlying
fungating solid mass measuring 8.5 cm. Serial sections revealed a hemorrhagic,
spongy, and granular cut surface. Histologically, the epidermis was hyperplastic,
with underlying hyaline collagen bundles. The remainder of the mass was
chronically inflamed and composed of spindled histiocytes, hemosiderin-laden
macrophages, and blood-filled spaces lacking an endothelial lining. There was
focal pleomorphism but no significant atypia. Immunohistochemical stains were
strongly positive for vimentin and negative for CD31, CD34, and desmin. The
overall architecture and immunophenotype are consistent with the diagnosis of
aneurysmal benign fibrous histiocytoma.
PMID- 29956350
TI - Panobinostat in combination with rituximab in heavily pretreated diffuse large B
cell lymphoma: Results of a phase II study.
AB - This is a phase II study of panobinostat, an oral pan-HDAC inhibitor, combined
with rituximab in patients with relapsed diffuse large B cell lymphoma.
Panobinostat was administered orally 3 times a week every other week on a 28-day
cycle. Rituximab was administered weekly during the first cycle, then on Day 1 of
cycles 2 to 6. Patients without disease progression after 6 cycles continued
panobinostat monotherapy for up to 6 additional cycles in the absence of disease
progression. Eighteen eligible subjects were enrolled, and 18 were evaluable for
response. The overall response rate was 11% (90% CI [2%-34%]) with 2 subjects
having a partial response. The duration of response in these subjects was 51 and
60 days. Five additional subjects had stable disease with 3 subjects having tumor
reduction between 27 and 44%, not meeting criteria for partial response. One
subject with stable disease remained on therapy a total of 12 cycles. The most
common toxicities while on study were thrombocytopenia (14 patients, 78%);
fatigue (11, 61%); anemia (10, 56%); diarrhea (8, 44%); and nausea, lymphopenia,
anorexia, and hypophosphatemia (5 each, 28% of patients), the majority of which
was grade 2 or less. These data indicate that the combination of panobinostat
with rituximab is able to induce responses in a limited number of subjects with
relapsed diffuse large B cell lymphoma.
PMID- 29956352
TI - Stereotype content and morality: How competence and warmth arise from morally
significant interactions.
AB - Stereotypes about many groups fall along two dimensions, one relating to
agency/competence and the other morality/warmth. This paper integrates research
and theory on stereotype contents and mind perception to explore how stereotypes
of competence and warmth are linked to perceptions of moral agency and patiency.
Competence identifies the moral agent, and warmth both identifies the moral
patient and describes the moral valence of the interaction. In two experimental
tests, a simple animated film showing circles and squares interacting in various
ways elicited predicted competence and warmth stereotypes that tracked perceived
moral valence. Integrating stereotype contents and mind perception literatures
offers new ways to think about the origins, functions, and dynamics between
dimensions of stereotype content.
PMID- 29956353
TI - DNA methylation assay based on pyrosequencing for determination of smoking
status.
AB - The goal of this study was to utilize pyrosequencing to identify CpG sites
indicative of tobacco smoking using DNA sequences surrounding ten frequently
reported smoking-related CpGs. Initially, six genetic loci were investigated
including AHRR, 2q37, 6p21.33, GFI1, F2RL3, and MYO1G in order to detect novel
CpG sites associated with tobacco smoking. The methylation data revealed a set of
23 consecutive CpG sites in blood (Chr5:373,115-Chr5:373,653) that were
significantly hypomethylated in current smokers. In addition, 10 of these 23 CpGs
were also significantly hypomethylated in the saliva of current smokers. The most
significant CpG sites were located at Chr5:373,490 in blood and Chr5:373,476 in
saliva with a decrease in methylation in current smokers of 42.3% and 21.3%
respectively. In the model-building steps of this study, a quick 4-CpG assay was
developed. The assay consisted of the top ranked CpG sites in blood and saliva.
The assay was applied in a leave-one-out approach to test its ability to infer an
individual's self-identified history of smoking habits. A multinomial logistic
regression model (MLR) containing all 4 CpG sites gave the most accurate results
in blood and saliva. In blood, the model correctly predicted 90.0% of current
smokers, 66.7% of former smokers, and 84.9% of never smokers. In addition, the
MLR model correctly predicted 86.9% of current smokers, 54.5% of former smokers,
and 77.8% of never smokers in saliva. These results demonstrate that this
pyrosequencing-based assay can provide an effective tool for identifying
individuals who smoke tobacco, particularly when using epigenetic markers in
blood.
PMID- 29956354
TI - Concomitant use of sorafenib with ombitasvir/paritaprevir/ritonavir and
dasabuvir: Effectiveness and safety in clinical practice.
AB - WHAT IS KNOWN AND OBJECTIVE: No studies have evaluated the use of sorafenib with
the direct-acting antiviral ombitasvir/paritaprevir/ritonavir and dasabuvir
(OBV/PTV/r+DSV). CASE SUMMARY: Three hepatitis C virus genotype 1b-infected
patients with well-preserved liver function were included in this prospective
case series. The patients were taking sorafenib for advanced hepatocellular
carcinoma and received OBV/PTV/r+DSV for 12 weeks. One patient discontinued
sorafenib while concomitant treatment due to grade 2 fatigue and muscular pain.
The other two patients reported only grade 1 adverse effects. Sustained virologic
response at 24 weeks was achieved, and no tumour recurrences were found. WHAT IS
NEW AND CONCLUSION: The concurrent use of OBV/PTV/r+DSV with sorafenib was
considered safe and effective.
PMID- 29956355
TI - Candida catenulata Candidaemia and Possible Endocarditis in a Cirrhotic Patient
Successfully De-escalated to Oral Fluconazole.
AB - WHAT IS KNOWN AND OBJECTIVE: Candida catenulata is a fungus commonly found in
Australian cheeses. C. catenulata has been identified as the causative pathogen
for one report of onychomycosis and one report of candidaemia. CASE DESCRIPTION:
A 37-year-old male underwent surgery for an incarcerated umbilical hernia repair
and bowel obstruction and presented with severe abdominal pain and ascitic fluid
draining from the surgical site. C. catenulata was isolated in blood cultures.
The patient was treated with antifungal therapy for approximately 6 weeks. WHAT
IS NEW AND CONCLUSION: To our knowledge, this is the first case describing
successful treatment of possible fungal endocarditis caused by C. catenulata.
PMID- 29956357
TI - The effect of body weight on intravenous diltiazem in patients with atrial
fibrillation with rapid ventricular response.
AB - WHAT IS KNOWN AND OBJECTIVES: To assess the effect of body weight on the total
dose of intravenous (IV) diltiazem needed to reach goal heart rate (HR) for
atrial fibrillation (Afib) with rapid ventricular response (RVR) in the emergency
department (ED) setting. METHODS: A single-center retrospective cohort was
ascertained using electronic medical record data from January 2013 to December
2016. Inclusion criteria consisted of new onset Afib with RVR, receipt of IV
diltiazem in the ED, and age >=18 years old. The primary outcome was the total
dose of diltiazem needed to reach goal HR <100, stratified by patients who were
<100 kg and those >=100 kg. The secondary outcome was the total time required to
reach goal HR. Demographic, clinical and medication-related data were collected,
including selected safety endpoints. RESULTS AND DISCUSSION: A total of 328
patients were included. Patients required a mean of 30.1 mg (+/-24.6) of
diltiazem and 2.3 hours (+/-2.9) to reach goal HR. The total dose of diltiazem
was similar for patients <100 kg and >=100 kg (28.7 vs 34.3 mg; P = .068) as was
the time to reach goal HR (2.3 vs 2.3 hours; P = .949), respectively. No
differences were noted in incidence of hypotension, bradycardia or need for
additional rate control agents. WHAT IS NEW AND CONCLUSION: No difference in the
total amount of diltiazem or time to reach goal HR was found in patients
according to body weight stratification.
PMID- 29956356
TI - A five-CpG DNA methylation score to predict metastatic-lethal outcomes in men
treated with radical prostatectomy for localized prostate cancer.
AB - BACKGROUND: Prognostic biomarkers for localized prostate cancer (PCa) could
improve personalized medicine. Our group previously identified a panel of
differentially methylated CpGs in primary tumor tissue that predict disease
aggressiveness, and here we further validate these biomarkers. METHODS:
Pyrosequencing was used to assess CpG methylation of eight biomarkers previously
identified using the HumanMethylation450 array; CpGs with strongly correlated (r
>0.70) results were considered technically validated. Logistic regression
incorporating the validated CpGs and Gleason sum was used to define and lock a
final model to stratify men with metastatic-lethal versus non-recurrent PCa in a
training dataset. Coefficients from the final model were then used to construct a
DNA methylation score, which was evaluated by logistic regression and Receiver
Operating Characteristic (ROC) curve analyses in an independent testing dataset.
RESULTS: Five CpGs were technically validated and all were retained (P < 0.05) in
the final model. The 5-CpG and Gleason sum coefficients were used to calculate a
methylation score, which was higher in men with metastatic-lethal progression (P
= 6.8 * 10-6 ) in the testing dataset. For each unit increase in the score there
was a four-fold increase in risk of metastatic-lethal events (odds ratio, OR =
4.0, 95%CI = 1.8-14.3). At 95% specificity, sensitivity was 74% for the score
compared to 53% for Gleason sum alone. The score demonstrated better prediction
performance (AUC = 0.91; pAUC = 0.037) compared to Gleason sum alone (AUC = 0.87;
pAUC = 0.025). CONCLUSIONS: The DNA methylation score improved upon Gleason sum
for predicting metastatic-lethal progression and holds promise for risk
stratification of men with aggressive tumors. This prognostic score warrants
further evaluation as a tool for improving patient outcomes.
PMID- 29956358
TI - Sustained Deterioration of Hepatic Oxygenation After Nafamostat Mesilate-Induced
Anaphylactic Shock During Hemodiafiltration.
PMID- 29956359
TI - Recent Achievements in Bone and Skin Tissue Engineering in Iran.
PMID- 29956360
TI - Are there health benefits of being unionized in late career? A longitudinal
approach using HRS.
AB - OBJECTIVE: To assess whether unionization prevents deterioration in self-reported
health and depressive symptoms in late career transitions. METHODS: Data come
from the Health and Retirement Study (N = 6475). The change in self-perceived
health (SPH) and depressive symptoms (CESD) between wave 11 and wave 12 is
explained using an interaction effect between change in professional status from
wave 10 to wave 11 and unionization in wave 10. RESULTS: The odds of being
affected by a negative change in CESD when unionized are lower for unionized
workers remaining in full-time job (OR:0.73, CI95%:0.58;0.89), unionized full
time workers moving to part-time work (OR:0.66, CI95%:0.46;0.93) and unionized
full-time workers moving to part-retirement (OR:0.40, CI95%:0.34;0.47) compared
to non-unionized workers. The same conclusion is made for the change in SPH but
with odds ratios closer to 1. CONCLUSION: The reasons for the associations found
in this paper need to be explored in further research.
PMID- 29956361
TI - Cardiac resynchronization therapy resulting from atrial pacing: An unusual case
of intraventricular conduction delay.
AB - Cardiac resynchronization therapy device implantation is complicated by a
significant rate of failure to place a left ventricular lead via the coronary
sinus. The present case describes one such failure ironically leading to
resynchronization. The patient's QRS narrowing subsequent to postimplant atrial
pacing alone suggests that bradycardia-dependent phase 4 block was the indirect
but exclusive cause of the patient's intraventricular conduction delay. Thus,
phase 4 block should be considered when atrial pacing at a faster rate resolves a
wide QRS interval.
PMID- 29956362
TI - Meta-analysis evaluating resting laryngeal endoscopy as a diagnostic tool for
recurrent laryngeal neuropathy in the equine athlete.
AB - BACKGROUND: Resting endoscopy has commonly been used as a method to predict
laryngeal function at exercise. OBJECTIVES: To perform a meta-analysis to
determine the sensitivity and specificity of resting laryngeal endoscopy to
predict clinical recurrent laryngeal neuropathy at exercise. STUDY DESIGN: Meta
analysis. METHODS: Manuscripts were included if data were available for both
resting and exercising airway function on all or a subset of horses. Normal
resting endoscopy was defined as laryngeal grades 1 or 2 on a 4-/7-point scale or
1, 2 or 3 on a 5-point scale and normal dynamic endoscopy as a dynamic laryngeal
grade A. RESULTS: Twelve studies including 1827 horses were evaluated. A small
proportion of horses with grade 1 or grade 2 laryngeal function at rest, 3.5 and
11.9%, respectively, were identified as having abnormal laryngeal function at
exercise. Within the horses with grade 3 laryngeal function at rest, 16% were
classified as grade A, 26.4% as grade B and 57.6% as grade C at exercise.
Worsening subgrades within resting grade 3 demonstrated an increasing proportion
of complete or partial paralysis at exercise. The sensitivity and specificity of
resting endoscopy was 74.4 and 95.1%, respectively, and the positive and negative
predictive values were 85.6 and 90.5% respectively. MAIN LIMITATIONS: Use of two
separate grading systems for evaluating resting laryngeal function. Other forms
of dynamic airway collapse were not evaluated. CONCLUSIONS: Resting endoscopy is
sensitive and highly specific for predicting laryngeal function at exercise.
Dynamic endoscopy is important to assess multiple causes of airway collapse.
PMID- 29956363
TI - Squamous cell carcinomas in linear epidermal naevi.
PMID- 29956365
TI - Properties of composite time to first event versus joint marginal analyses of
multiple outcomes.
AB - Many clinical studies (eg, cardiovascular outcome trials) investigate the effect
of an intervention on multiple event time outcomes. The most common method of
analysis is a so-called "composite" analysis of a composite outcome defined as
the time to the first component event. Other approaches have been proposed,
including the win ratio (or win difference) for ordered outcomes and the
application of the Wei-Lachin test. Herein, we assess the influence of the
marginal and joint distributions of the component events, and their correlation
structures, on the operating characteristics of these methods for the analysis of
multiple events. The operating characteristics are investigated using a bivariate
exponential model with a shared frailty, under which these properties are
obtained in closed form. While the composite time-to-first-event analysis
provides an unbiased test of the hypothesis of equality of the distribution of
the time to first event, we show that it can provide a biased test of the joint
null hypothesis of equal marginal hazards when the correlation of event times
differs between groups. The same applies to the win ratio. However, the operating
characteristics of the Wei-Lachin or other tests of the joint equality of the
marginal hazards are unaffected. Furthermore, when the correlations are equal,
the Wei-Lachin test is more powerful to detect a difference in marginal hazards
than the composite analysis test. Careful consideration of the properties of the
various methods for analysis of composite outcome measures are in order before
adopting one as primary analysis in a clinical study.
PMID- 29956364
TI - Availability of cookies during an academic course session affects evaluation of
teaching.
AB - OBJECTIVES: Results from end-of-course student evaluations of teaching (SETs) are
taken seriously by faculties and form part of a decision base for the recruitment
of academic staff, the distribution of funds and changes to curricula. However,
there is some doubt as to whether these evaluation instruments accurately measure
the quality of course content, teaching and knowledge transfer. We investigated
whether the provision of chocolate cookies as a content-unrelated intervention
influences SET results. METHODS: We performed a randomised controlled trial in
the setting of a curricular emergency medicine course. Participants were 118
third-year medical students. Participants were randomly allocated into 20 groups,
10 of which had free access to 500 g of chocolate cookies during an emergency
medicine course session (cookie group) and 10 of which did not (control group).
All groups were taught by the same teachers. Educational content and course
material were the same for both groups. After the course, all students were asked
to complete a 38-question evaluation form. RESULTS: A total of 112 students
completed the evaluation form. The cookie group evaluated teachers significantly
better than the control group (113.4 +/- 4.9 versus 109.2 +/- 7.3; p = 0.001,
effect size 0.68). Course material was considered better (10.1 +/- 2.3 versus 8.4
+/- 2.8; p = 0.001, effect size 0.66) and summation scores evaluating the course
overall were significantly higher (224.5 +/- 12.5 versus 217.2 +/- 16.1; p =
0.008, effect size 0.51) in the cookie group. CONCLUSIONS: The provision of
chocolate cookies had a significant effect on course evaluation. These findings
question the validity of SETs and their use in making widespread decisions within
a faculty.
PMID- 29956366
TI - Active zone structure-function relationships at the neuromuscular junction.
AB - The impact of presynaptic transmitter release site organization on synaptic
function has been a vibrant area of research for synaptic physiologists. Because
there is a highly nonlinear relationship between presynaptic calcium influx and
subsequent neurotransmitter release at synapses, the organization and density of
calcium sources (voltage-gated calcium channels [VGCCs]) relative to calcium
sensors located on synaptic vesicles is predicted to play a major role in shaping
the dynamics of neurotransmitter release at a synapse. Here we review the history
of structure-function studies within transmitter release sites at the
neuromuscular junction across three model preparations in an effort to discern
the relationship between VGCC organization and synaptic function, and whether
that organizational structure imparts evolutionary advantages for each species.
PMID- 29956367
TI - Brummer-dependent lipid mobilization regulates starvation resistance in
Nilaparvata lugens.
AB - Energy homeostasis is an essential characteristic of all organisms, requiring
fluctuation in energy accumulation, mobilization, and exchange with the external
environment. In insects, energy mobilization is under control of the lipase
brummer (bmm), which regulates nutritional status by hydrolyzing the ester bonds
in triacylglycerol (TAG). In the present study, we investigated the role of bmm
in the lipid mobilization and starvation resistance in the brown planthopper
(BPH; Nilaparvata lugens), which is economically one of the most important rice
pests in Asia. A severe decrease in TAG and glyceride contents was observed in
the starved BPHs, while there was a partial rescue after refeeding. The
starvation condition caused a significant increase in the expression levels of
Nlbmm, and supplement of food after starvation dramatically reduced the Nlbmm
expression. Sucrose rescue after starvation significantly suppressed the
expression of Nlbmm, while caused an accumulation of TAG and glyceride. Knockdown
of Nlbmm by double-stranded RNA treatment extended the lifespan to starvation,
whereas it increased the level of TAG and glyceride in the BPHs. The decreased
lipolysis rate by dsNlbmm-treated BPHs eventually resulted in increase of
starvation resistance. These data demonstrated that the regulation of energy
homeostasis by Nlbmm affects starvation resistance, probably through lipid
mobilization control in N. lugens.
PMID- 29956368
TI - Functional dentition and associated factors in Brazilian elderly people: A
multilevel generalised structural equation modelling approach.
AB - INTRODUCTION: The objective of the present study was to evaluate the association
of socioeconomic status (SES) as a latent variable on oral health-related quality
of life (OHRQoL) using four definitions of functional dentition (FD) for elderly
people. METHODS: Four sets of multilevel generalised structural equation models
(GSEM) were used: (i) WHO Functional Dentition (FDWHO); (ii) Well-distributed
teeth (WDT); (iii) FDclass5 ; and (iv) FDclass6 . The indirect effects of SES on
OHRQoL were measured in 5951 elderly participants in the Sao Paulo Oral Health
2015 (SBSP-15) survey. The latent variable (OHRQoL) was extracted from the Oral
Impacts on Daily Performances questionnaire, and GSEM was used to estimate the
direction of association among the variables. RESULTS: SES was directly and
strongly associated with FDWHO (Total effects [SC] = 0.56, P < .001); WDT (Total
Effects [SC] = 0.55, P < .001); FDclass5 (Total effects [SC] = 0.07, P < .001);
and FDclass6 (Total effects [SC] = 0.05, P = .001). All FD outcomes mediate
effects of SES on OHRQoL (P < .05). SES had a direct effect on happiness which,
in turn, had a direct effect on OHRQoL ([SC] = 0.05, P < .001). CONCLUSIONS: All
definitions of FD were good at mediating the effects of SES on OHRQoL, showing
the importance of occlusal and periodontal statuses of elderly individuals.
PMID- 29956369
TI - Salivary hypofunction: An update on therapeutic strategies.
AB - OBJECTIVE: To perform a literature review addressing the therapeutic strategies
for salivary hypofunction. BACKGROUND: Qualitative and quantitative salivary
dysfunctions predispose to changes in the oral mucosa and teeth, cause impairment
to oral functions and negative impact on quality of life. MATERIALS AND METHODS:
A MEDLINE/PubMed search was conducted using the terms "Xerostomia" AND, "Saliva
Artificial" OR, "Citric Acid," "Malic Acid," "Chewing Gum," "Acupuncture" OR,
"Pilocarpine" OR, "Bethanechol" OR, "Cevimeline" OR, "Hyperbaric Oxygen Therapy"
OR, "Stem Cell Therapy" OR "Genetic Therapy" and their Mesh Terms. RESULTS: We
selected 25 clinical trials investigating the effects of salivary substitutes,
chewing gum, malic and citric acids, pilocarpine, cevimeline, bethanechol,
acupuncture, hyperbaric oxygen therapy and regenerative therapies on salivary
hypofunction. In most studies, the number of participants was low and the follow
up times short. The therapeutic modalities were classified according to the level
of evidence on salivary dysfunction. CONCLUSIONS: Pilocarpine and cevimeline had
the strongest evidence of beneficial effect on salivary hypofunction. Citric and
malic acids increase salivary flow but also increase the risk of erosion and
dental caries. There are no controlled clinical trials supporting the efficacy of
acupuncture, stem cell therapy and gene therapy on salivary dysfunction, although
clinical observations suggest a promising effect. There is no evidence supporting
salivary substitutes, chewing gum, bethanechol or hyperbaric oxygen on the
treatment of salivary hypofunction.
PMID- 29956370
TI - When should iron supplementation in dialysis patients be avoided, minimized or
withdrawn?
AB - Parenteral iron is used to restore the body's iron pool before and during
erythropoiesis-stimulating agent (ESA) therapy; together these agents form the
backbone of anemia management in end-stage renal disease (ESRD) patients
undergoing hemodialysis. ESRD patients receiving chronic intravenous iron
products, which exceed their blood loss are exposed to an increased risk of
positive iron balance. Measurement of the liver iron concentration (LIC) reflects
total body iron stores in patients with secondary hemosiderosis and genetic
hemochromatosis. Recent studies of LIC in hemodialysis patients, measured by
quantitative MRI and magnetic susceptometry, have demonstrated a high risk of
iron overload in dialysis patients treated with IV iron products at doses
advocated by current anemia management guidelines for dialysis patients. Liver
iron overload causes increased production of hepcidin and elevated plasma levels,
which can activate macrophages of atherosclerotic plaques. This mechanism may
explain the results of 3 long-term epidemiological studies which showed the
association of excessive IV iron doses with increased risk of cardiovascular
morbidity and mortality among hemodialysis patients. A more physiological
approach of iron therapy in ESRD is needed. Peritoneal dialysis patients,
hemodialysis patients infected with hepatitis C virus, and hemodialysis patients
with ferritin above 1000 MUg/L without a concomitant inflammatory state, all
require specific and cautious iron management. Two recent studies have shown that
most hemodialysis patients will benefit from lower maintenance IV iron dosages;
their results are applicable to American hemodialysis patients. Novel
pharmacometric and economic approaches to iron therapy and anemia management are
emerging which are designed to lessen the potential side effects of excessive IV
iron while maintaining hemoglobin stability without an increase in ESA dosing.
PMID- 29956371
TI - Social health insurance vs private health insurance in China: Revisit crowd-out
effect based on a multiple mediation analysis.
AB - Plenty of scholars have studied social health insurance and private health
insurance in different economies, and many concentrate on crowd-out effect.
Different results have been presented due to various data choices and empirical
methodologies, but few of them have revealed the transaction mechanism. We study
this issue based on updated Chinese provincial panel data from 2002 to 2014 and
improved methods. We focus on how the crowd-out effect happens through 3 channels
saving, demographic factor, and medical expenditure using multiple mediator
models. Besides, we apply Panel VAR model to study magnitude of the impact these
3 channels contribute, corporately and respectively. Results clearly show that
social health insurance has crowd-out effect in penetration but crowd-in effect
in density caused by different mediation variables. In addition, the 3 channels
have shown lasting and dynamic influences on the crowd-out (in) effect. Finally,
our paper provides the anti-crowd-out solutions from both perspectives according
to our empirical analyses. For social health insurance system, it is necessary to
improve the efficiency and fairness of the funds. For the private health
insurance companies, insurance products innovation and privilege policy should be
made to decrease the negative impact of saving and medical service overuse.
PMID- 29956372
TI - Level of interobserver variability estimation as a valuable tool: assessment of
tumour budding in colon cancer.
AB - AIMS: Tumour budding is considered to be a good marker for progression and
prognosis in colorectal carcinomas. A uniform classification system has been
established recently. The natural element of uncertainty in the practice of human
medicine is also exhibited in the assessment of tumour budding. We tested the
hypothesis that interobserver variability can be estimated during the assessment
process and investigated its potential clinical implication. METHODS AND RESULTS:
Six investigators with different levels of experience could perceive different
levels of difficulty (LOD) and estimated different levels of interobserver
variability (LOIV) (Li1, lower than average; Li2, average; Li3, higher than
average) during the assessment of tumour budding in 244 cases of colon cancer
(pT3/4). In total, the LOIV showed following distribution: Li1: 36.1%, Li2: 43.9%
and Li3: 20.0%. The LOIV was correlated significantly with the LOD given by the
investigator. In total, the agreement rates with the final consensus
classification were: Li1: 93.4%, Li2: 78.5% and Li3: 58.4%. The relative risk of
disagreement with the final consensus classification was more than six times
higher when a case was estimated to have a high rather than a low interobserver
variability. CONCLUSION: Our data show that the investigator can estimate the
interobserver variability during the ongoing rating process in pT3/4 colon
cancer. The LOIV/LOD seems to be a valuable parameter of the assessment quality.
For Li3 cases further measures seem mandatory.
PMID- 29956373
TI - A random forest and simulation approach for scheduling operation rooms: Elective
surgery cancelation in a Chinese hospital urology department.
AB - Many hospitals encounter surgery cancelations for various reasons. We present a
methodology applying data mining and simulation to optimize operating room (OR)
scheduling in a urology department in West China Hospital. To the best of our
knowledge, this is 1 of the first efforts to seek an optimal schedule solution
based on cancelation risk of elective surgeries as well as OR allocation between
elective and nonelective surgeries. First, chi-square test and random forest
prediction modeling were used to predict potential elective surgeries with high
cancelation risk, and the factors, including surgeon, number of days since
admission of patient, first surgery or not, etc., that influence elective surgery
cancelation were identified. Second, a simulation technology was designed to
compare 7 different scheduling strategies. The results demonstrated that for
elective surgery, cancelation rate low surgery first outperformed the others and
increased the productivity of the ORs from 72% to 83%, while for nonelective
surgery performed in a separate OR, there was no improvement because the supply
was greater than necessary at present. However, in total, the selected strategies
led to 7% higher productivity.
PMID- 29956374
TI - Public perception of river fish biodiversity in four European countries.
AB - Public support for biodiversity conservation is shaped by people's values and
their knowledge, beliefs, and attitudes toward the environment. We conducted the
first multinational representative survey of the general public's perceptions of
river fish biodiversity in France, Germany, Norway, and Sweden. For the online
survey, 1000 respondents per country were randomly selected from large panels
following country-specific quotas set on age, gender, and educational level.
Questions covered people's level of knowledge, beliefs, values, and attitudes
toward river fish, environmental threats, and conservation measures. We found
that the public had limited knowledge of freshwater fishes. Two non-native
species, rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinus
fontinalis), were widely perceived as native, whereas native Atlantic salmon
(Salmo salar) was mostly classified as native in Scandinavia and largely as non
native in central Europe. These results suggest an extinction of experience
paralleling the extirpation or decline of salmon stocks in countries such as
Germany and France. Respondents thought pollution was the dominant threat to
riverine fish biodiversity. In reality, habitat loss, dams, and the spread of non
native fishes are equally important. Despite limited biological knowledge,
respondents from all countries held an overwhelmingly proecological worldview,
supported conservation stocking, and appreciated native fishes, although only a
minority interacted with them directly. Differences among the 4 countries related
to several conservation issues. For example, threats to biodiversity stemming
from aquaculture were perceived as more prevalent in Norway compared with the
other 3 countries. Promoting fish conservation based on charismatic species and
use values of fishes may work well in countries with a strong economic and
cultural link to the freshwater environment, such as Norway. In countries where
people rather abstractly care for nature, focusing conservation messaging on
broader ecosystem traits and non-use values of fishes is likely to win more
support.
PMID- 29956375
TI - How might organisational institutionalism support the challenges of the modern
hospice?
AB - The external environment within which UK charitable hospice care operates is
changing. More people are dying with conditions other than cancer; however, this
disease still dominates modern hospice care. Organisational institutionalism
offers a theoretical lens through which to consider the challenges facing the
hospice movement. Concepts such as legitimacy, decoupling,
deinstitutionalisation, and reinstitutionalisation can help hospice leaders
understand the challenges of change and some of the strategies that can be
employed at local and national levels. This paper outlines a number of
environmental and influencing factors driving and impacting change. A model of
institutional change is introduced, explored, and considered from the context of
hospice. When it comes to understanding change, legitimacy is a major concept
introduced to challenge and pose questions for hospices to address. This paper
proposes a model demonstrating a perspective regarding the current structure of
services within hospice organisations. The model argues that only hospice care
for people with cancer is truly institutionalised and that other areas of care
lack comparable legitimacy. It provides 3 directions for hospice in addressing
the challenges faced: (i) decoupling, (ii) deinstitutionalisation then
reinstitutionalisation, and (iii) a new social movement. The paper concludes with
recommendations for future consideration.
PMID- 29956376
TI - High jump demands in professional volleyball-large variability exists between
players and player positions.
AB - Training volume has been associated with jumper's knee in volleyball players, but
jump variability among professionals has not been investigated and individual
jump demands are unknown. The purpose of this study was to examine position
specific jump demands required for training and competition during a professional
volleyball season and to investigate the individual variability associated with
jump load. Jumps performed by 14 professional players during one season of
training and competition were timestamped, individually assigned, and recorded
for jump height. Jump counts, heights, and frequency were analyzed to determine
the specific jump load performed by players at each position during training and
match play. A total of 129 173 jumps were performed during 142 sessions (108
practices, 27 matches, 7 friendly matches). Setters performed the greatest volume
of jumps (121 jumps/training session). Opposites performed more high-intensity
jumps than their teammates (median season jump height: 69% of maximum).
Substantial weekly jump count variability was observed, 18 of 28 weeks included
at least one player with a twofold increase in jump load or a player returning to
volleyball after performing no jumps the previous week. Additionally, each player
had at least 1 week with a twofold increase in jumps. Jump demands are high in
professional volleyball, and performance programs should be tailored to the match
and training demands required at each position. Jump loads are highly variable
substantial week-to-week increases were observed for both the team and individual
players. As a result, monitoring individual jump load seems necessary.
PMID- 29956377
TI - Usefulness of thrombopoietin receptor agonists for persistent clinically relevant
thrombocytopenia after allogeneic stem cell transplantation.
AB - OBJECTIVE AND METHODS: Severe postengraftment thrombocytopenia is a common
complication after allogeneic stem cell transplantation (alloSCT). A few studies
have suggested that the use of thrombopoietin agonists (TPOa) may be useful in
this setting. Our retrospective study is the largest series published to date; we
retrospectively evaluated TPOa efficacy and safety in 20 adult alloSCT recipients
who received TPOa as a compassionate use for clinically relevant
thrombocytopenia. RESULTS: Twelve of 20 patients (60%) responded, with a 180-day
cumulative incidence of successful platelet recovery to >=30 and >=50 * 109 /L of
57% (95% CI: 44%-71%) and 32% (95% CI: 18%-46%), respectively, which were reached
at a median of 28 and 34 days from the start of therapy. Fifty percent of the
responders were able to discontinue the TPOa without recurrence of severe
thrombocytopenia and its associated hemorrhagic complications. No serious adverse
events were reported. Possible variables associated with higher response to TPOa
were as follows: age < 40 years, presence of megakaryocytes in the bone marrow
aspirate, and/or prior response to other hematopoietic growth factors.
CONCLUSION: This study adds further enthusiasm for continued research on the use
of these agents for the treatment of persistent thrombocytopenia in alloSCT
recipients.
PMID- 29956378
TI - Brexit and transplantation does anyone win?
PMID- 29956379
TI - Cytomegalovirus infection and graft rejection as risk factors for pneumocystis
pneumonia in solid organ transplant recipients: A systematic review and meta
analysis.
AB - A growing number of publications have reported the outbreaks of post-transplant
pneumocystis pneumonia (PJP). In most studies, the onset of PJP was beyond 6-12
months of prophylaxis. Cytomegalovirus (CMV) infection and allograft rejection
have been repeatedly reported as probable risk factors for post-transplant PJP.
In this systematic review and meta-analysis, we determined the pooled effect
estimates of these 2 variables as risk factors. Data sources included PUBMED,
MEDLINE-OVID, EMBASE-OVID, Cochrane Library, Networked Digital Library of Theses
and Dissertations, World Health Organization, and Web of Science. We excluded
publications related to hematopoietic stem cell transplantation (HSCT) or Human
Immunodeficiency Virus (HIV) patients. Eventually, 15 studies remained for the
final stage of screening. Cytomegalovirus infection (OR: 3.30, CI 95%: 2.07-5.26,
I2 : 57%, P = 0.006) and allograft rejection (OR:2.36, CI95%: 1.54-3.62, I2:
45.5%, P = 0.05) significantly increased the risk of post-transplant PJP.
Extended prophylaxis targeting recipients with allograft rejection or CMV
infection may reduce the risk of PJP.
PMID- 29956380
TI - CPSE determination and detection of canine prostatic diseases: The importance of
a specific diagnosis.
PMID- 29956381
TI - Flexible Nanoparticles Reach Sterically Obscured Endothelial Targets Inaccessible
to Rigid Nanoparticles.
AB - Molecular targeting of nanoparticle drug carriers promises maximized therapeutic
impact to sites of disease or injury with minimized systemic effects. Precise
targeting demands addressing to subcellular features. Caveolae, invaginations in
cell membranes implicated in transcytosis and inflammatory signaling, are
appealing subcellular targets. Caveolar geometry has been reported to impose a
~50 nm size cutoff on nanocarrier access to plasmalemma vesicle associated
protein (PLVAP), a marker found in caveolae in the lungs. The use of deformable
nanocarriers to overcome that size cutoff is explored in this study. Lysozyme
dextran nanogels (NGs) are synthesized with ~150 or ~300 nm mean diameter. Atomic
force microscopy indicates the NGs deform on complementary surfaces. Quartz
crystal microbalance data indicate that NGs form softer monolayers (~60 kPa) than
polystyrene particles (~8 MPa). NGs deform during flow through microfluidic
channels, and modeling of NG extrusion through porous filters yields sieving
diameters less than 25 nm for NGs with 150 and 300 nm hydrodynamic diameters. NGs
of 150 and 300 nm diameter target PLVAP in mouse lungs while counterpart rigid
polystyrene particles do not. The data in this study indicate a role for
mechanical deformability in targeting large high-payload drug-delivery vehicles
to sterically obscured targets like PLVAP.
PMID- 29956382
TI - Consideration of appropriate clinical applications for cardiac
xenotransplantation.
AB - The field of cardiac xenotransplantation has entered an exciting era due to
recent advances in the field. Although several hurdles remain, the use of rapidly
evolving transgenic technology has the potential to address current allogeneic
donor pool constraints and mechanical circulatory system device limitations. The
success of xenotransplantation will undoubtedly be dependent on specific patient
selection criteria. Defining these particular indications for xenotransplantation
is important as we approach the possibility of clinical applications.
PMID- 29956383
TI - Participation in organized sports is associated with decreased likelihood of
unhealthy lifestyle habits in adolescents.
AB - Adolescence is a pivotal time for investing in both present and future health.
Thus, it is important to identify arenas for promoting positive adolescent health
behaviors and preventing negative ones. The aim of this study was to investigate
the associations between organized sports participation (OSP) and a broad range
of lifestyle habits in Norwegian adolescents. A comprehensive survey was
completed by 13 269 junior high and high school students in southern Norway.
Multivariable binary logistic regression models, adjusted for gender, age, and
parental education, were used to investigate the associations between OSP and
adolescent substance use, dietary habits, physical activity level, passive vs
active transportation, screen time, and sleep duration. Inverse associations were
found between OSP and adolescent substance use (odds ratio 0.40 [95% confidence
interval 0.30-0.52] to 0.68 [0.61-0.76]), irregular consumption of main meals
(0.58 [0.53-0.63] to 0.78 [0.70-0.89]), high intake of unhealthy food and
beverages (0.55 [0.47-0.65] to 0.86 [0.75-0.98]), low intake of healthy food
items (0.57 [0.51-0.63] to 0.77 [0.70-0.84]), low physical activity level (0.15
[0.14-0.17]), high screen-based activity (0.61 [0.55-0.67]), passive vs active
transportation (summer; 0.79 [0.72-0.86] and winter; 0.84 [0.77-0.92]), and short
sleep duration, during both weekdays (0.57 [0.52-0.63]) and weekends (0.79 [0.69
0.89]). In conclusion, adolescents participating in organized sports had
decreased odds for engaging in several unhealthy lifestyle habits compared with
non-participants, indicating that organized sports may be a relevant setting for
promoting healthy behaviors among adolescents. Future studies are, however,
needed to confirm a possible causal relationship.
PMID- 29956384
TI - Effects of five cryoprotectants on proliferation and differentiation-related gene
expression of frozen-thawed bovine calf testicular tissue.
AB - The cryopreservation of testicular tissue is a potential method for preserving
male fertility. However, the effect of cryopreservation on bovine calf testicular
tissue is scarce. This study investigated the effect of different cryoprotectants
on bovine calf testicular tissue at the molecular level. Testicular tissue from
ten immature bovine calves (6 months) was collected after slaughter and
cryopreserved in an extender containing different concentrations of the following
five cryopreservation solutions (CP): bovine serum albumin (BSA) with 5% dimethyl
sulfoxide (DMSO), trehalose with 5% DMSO, DMSO and glycerol and ethylene glycol
(EG). After 7-day cryopreservation, the expression levels of three spermatogonial
stem cell (SSC)-related genes, octamer-4 (OCT4), KIT ligand (MGF/SCF) and kit
oncogene (C-KIT), were investigated by quantitative PCR (qPCR). The cell
viability was highest for the tissues preserved with 30 mg/ml BSA (77.82% +/-
1.22) and 40 mg/ml trehalose (74.23% +/- 1.16) compared with other groups (p <
0.05), and the level of expression of the three genes was highest with 30 mg/ml
BSA (p < 0.05). Compared with other CPs, the 30 mg/ml BSA and 40 mg/ml trehalose
have the better cryopreserve protection. The 30 mg/ml BSA is the most viable
media for the cryopreservation of testicular tissue from cattle.
PMID- 29956385
TI - Duration of corticosteroid use and long-term outcomes after adult heart
transplantation: A contemporary analysis of the International Society for Heart
and Lung Transplantation Registry.
AB - BACKGROUND: Long-term corticosteroid (CS) maintenance remains an effective option
for immunosuppression following heart transplantation. We used the International
Society for Heart and Lung Transplantation Registry to examine characteristics
and long-term survival among heart transplant recipients with different duration
of CS therapy. METHODS: Primary adult heart recipients transplanted between 2000
and 2008 who survived at least 5 years were categorized into three groups
according to CS use: early withdrawal (<=2 years) (EARLY D/C), late withdrawal
(between 2 and 5 years) (LATE D/C), or long-term use (>5 years) (LONG-TERM).
Recipient and donor characteristics, post-transplant morbidities, and mortality
were compared among groups. Kaplan-Meier was used to estimate survival up to 10
years post-transplant. RESULTS: The study cohort included 8161 recipients (2043
in EARLY D/C; 2031 in LATE D/C; and 4087 in LONG-TERM). LONG-TERM use of CS
decreased over time, from 60% in 2000 to 43% in 2008, while EARLY D/C increased
from 19% to 33%, respectively. Survival at 10 years after transplant was lower
among the LONG-TERM group (73% vs EARLY D/C 82% vs LATE D/C 80%; P < 0.0001).
CONCLUSIONS: In this large multinational cohort, the practice of long-term CS
maintenance was associated with lower long-term survival compared with shorter CS
use.
PMID- 29956386
TI - From Tetraphenylfurans to Ring-Opened (Z)-1,4-Enediones: ACQ Fluorophores versus
AIEgens with Distinct Responses to Mechanical Force and Light.
AB - Two aryl-substituted tetraphenylfurans (TPF-1 and TPF-2) and the corresponding
ring-opened (Z)-1,4-enedione derivatives (TPBD-1 and TPBD-2) have been
successfully synthesized. Although all the molecules adopt propeller-like
configurations, experimental results revealed that the tetraphenylfurans (TPFs)
were aggregation-caused quenching (ACQ) fluorophores whereas the 1,4-enediones
(TPBDs) were aggregation-induced emission (AIE) active. Additionally, the TPFs
and TPBDs exhibited contrasting "turn-on" mechanochromic behavior, with an
unusual blueshift of mechanochromic fluorescence for the TPFs and a remarkable
redshifted mechanochromism for the TPBDs. Both of these solid-state optical
properties were proven to be highly dependent on the mode of molecular packing
and substituent effects. In particular, in addition to the tunability of the
fluorescent properties through aggregation and mechanical force, ground TPF-1 was
found to be efficiently sensitive to light. On the basis of these findings we
constructed a smart film with ground TPF-1 and demonstrated its utility in data
encryption and decryption well controlled by UV light. Therefore, this work not
only provides an insight into the mechanism of AIE as well as mechanochromic
effects, but also paves the way towards the development of multifunctional
stimuli-responsive materials and devices.
PMID- 29956387
TI - Modulation of seminal plasma content in extended semen improves the quality
attributes of ram spermatozoa following liquid preservation at 3-5 degrees C.
AB - Seminal plasma (SP) is known to induce motility and capacitation in spermatozoa
curtailing their lifespan when preserved. Hence, this study was conducted to
examine the effects of removal of SP from sperm surface prior to liquid
preservation either by high dilution (1/15) or by washing and the poststorage
treatment with SP (15% and 25%, v/v) on the quality attributes of liquid
preserved ram semen. Over the period of storage, the rapid motility (66.0% and
71.1% vs. 58.3%), straightness (87.1% and 82.1% vs. 79.4%), average path velocity
(152.3 and 152.0 um/s vs. 133.3 um/s) and the straight-line velocity (131.3 and
127.8 um/s vs. 108.5 um/s) were significantly (p < 0.05) higher in both the high
dilution and wash groups as compared to the control (1/3 dilution). The
functional membrane integrity (82.3% vs. 77.2%) and noncapacitated sperm count
(65.0% vs. 58.7%) were also significantly (p < 0.05) higher in the high-dilution
and wash groups, respectively, as compared to the control. The poststorage
treatment of sperm with SP significantly (p < 0.05) increased the functional
membrane integrity (70.1% vs. 53.8%) and most of the motility attributes as
compared to the control (without SP). In conclusion, both the removal of SP prior
to liquid preservation and poststorage treatment with SP significantly improved
the quality attributes of ram spermatozoa.
PMID- 29956388
TI - A rational and clinical echocardiographic approach to the severe neurologic
injury.
PMID- 29956389
TI - Quality of life after pelvic exenteration for gynecologic cancer: Findings from a
qualitative study.
AB - OBJECTIVE: Pelvic exenteration (PE) in carefully selected gynecologic cancer
patients has a 5-year survival rate as high as 60%. Thus, there is a growing
number of PE survivors dealing with the effects of this radical surgery. The
current study sought to explore women's physical, psychological, and social
quality of life (QOL) after PE. METHODS: Fourteen women who had undergone PE for
recurrent gynecologic cancer at least 1 year previously completed semistructured
qualitative interviews designed to elicit expectations and experiences of QOL
following PE. Thematic analysis was used to code transcripts for both a priori
and emergent themes. RESULTS: Themes included PE versus palliative care,
preparedness, persistent symptoms, the not so normal new normal, new rules of
social engagement, support, emotional diversity, and bouncing back through
adaptive coping. Key differences with previous studies include the explicit
acknowledgement of the need for palliative care, the chronic nature of multiple,
seemingly unaddressed physical symptoms in survivorship, and the predominance of
positive psychological symptoms. While a minority expressed emotional distress
and regret for undergoing PE, most articulated a sense of resilience gained
through a variety of adaptive coping strategies. CONCLUSIONS: Findings underscore
the persistent physical, psychological, and social effects of PE on QOL and the
need for comprehensive, multidisciplinary patient care before and long after
surgery. Findings should promote development of a best practice clinical pathway
for the care and education of women who undergo PE with curative intent for
gynecologic cancer.
PMID- 29956390
TI - Canine cryptorchidism: An update.
AB - This review article is aimed at providing an update on canine cryptorchidism
based on the research studies published in this area over the last 26 years.
Although a majority of these research studies were directed at investigating the
genetic and molecular basis of cryptorchidism, the mechanisms underlying this
problem in dogs are still not clear. Future studies using advanced genomic and
molecular approaches and including a larger number of dogs of multiple breeds are
required to further our understanding of canine cryptorchidism. Diagnosis and
treatment of cryptorchidism in dogs have not received much attention. Research
advancements include investigation of ultrasonography and anti-Mullerian hormone
assay as potential diagnostic methods. Advancements in treatment include the use
of laparoscopic-assisted cryptorchidectomy. Based on the available literature,
this method appears to be the best for removal of abdominal cryptorchid testes
from dogs. However, future studies that compare laparoscopic-assisted
cryptorchidectomy with the traditional approaches are required for a more
conclusive determination of the best method for cryptorchidectomy in dogs.
PMID- 29956391
TI - Social support and breast cancer screening in rural Appalachia.
AB - PURPOSE: Women in the Appalachian region have a high mortality rate attributable
to cancer in spite of lower incidence of cancer compared with the general US
population. Empirical evidence suggests that social support influences cancer
outcomes, including adherence to screening guidelines and treatment
recommendations. The purpose of this study is to examine the impact of social
support on breast cancer screening patterns in a sample of rural Appalachian
women. METHODS: This paper reports the results of analyses of baseline cross
sectional data on breast cancer screening collected during a community-based
group-randomized trial. We used the 2010 National Health Institute Survey
questionnaires and the Medical Outcomes Study Social Support Survey to assess
screening behavior and perceived social support, respectively. Data were analyzed
using ANCOVA and ANOVA to assess the mean social support on breast cancer
screening patterns (frequently, irregularly, and rarely/never) and relevant
sociodemographic variables. FINDINGS: Of the eligible participant records
analyzed (N = 289), 50% were married, 36% were employed, 20% attended college,
40% had no mammogram in 6 years, and 20% never had mammograms. Overall social
support score was high at 73.1 (SD = 18.2). Association between breast cancer
screening patterns and social support scores was not statistically significant at
alpha < 0.05 (P value = 0.09). CONCLUSIONS: Although social support as it
measured in this study does not show significant associations with screening
patterns, it is important to understand how social network structures may
influence screening patterns. Familial and social roles/responsibilities that
result in reported social support may also be the barrier to cancer screening and
other prevention health behaviors.
PMID- 29956392
TI - Enhancing clinical practice in the management of distress: The Therapeutic
Practices for Distress Management (TPDM) project.
AB - OBJECTIVE: The Therapeutic Practices for Distress Management (TPDM) project was
carried out to support clinicians in integrating recommendations from four
clinical practice guidelines (CPGs) in routine care at five Pan Canadian cancer
care sites. METHODS: Using a concurrent, mixed-method study design and knowledge
translation (KT) activities, this project included two phases: phase I-a
baseline/preparation phase and phase II-an intervention phase plus evaluation.
The intervention phase (the focus of this report) included a one-year education
and supervision program (24 hours in virtual class; 12-hour group supervision).
Primary outcomes were knowledge and self-efficacy in practicing CPGs as measured
by a Knowledge and Self-Efficacy Survey (KSES). A secondary outcome was observer
rated performances with standardized patients (objective structured clinical
exams). Participants included 80 (90%) nurses, and 9 (10%) social workers (N =
89). RESULTS: The TPDM program was effective in accomplishing change in
knowledge, self-efficacy, and performance. All measures demonstrated significant
change pre and post module, with evidence of increasing knowledge (P < .01) and
confidence (P < .01) over time. Further, there was evidence of a shift in
barriers and enablers to practicing in alignment with the CPGs. CONCLUSIONS: A
tailored education program using case-based learning and supervision over time
improves knowledge and practice among front line clinicians. The findings have
implications for quality improvement in cancer care.
PMID- 29956393
TI - Suicide rates among patients with cancers of the digestive system.
AB - OBJECTIVE: Previous studies have suggested that suicide rates are elevated among
cancer patients relative to the general population. In this analysis, we
comprehensively evaluated characteristics associated with higher suicide rates
among patients with cancers of the digestive system. METHODS: Using the United
States Surveillance, Epidemiology, and End Results database, we identified all
patients diagnosed with digestive system cancers during 2000 to 2014. Patients
were classified as having died of suicide if their cause of death in
Surveillance, Epidemiology, and End Results was listed as "suicide and self
inflicted injury." Suicide rates were compared to age-, sex-, and race-adjusted
rates in the general population. RESULTS: A total of 881 suicides were identified
among 856 293 patients diagnosed with digestive system cancers. The suicide rate
in this population was 32.8 per 100 000 person-years and was nearly twice that in
the general population (standardized mortality ratio [SMR] = 1.91; 95% CI, 1.79
2.04). Suicide rates were significantly elevated for all cancer sites but were
highest for esophageal (SMR = 5.03), pancreatic (SMR = 5.28), stomach (SMR =
2.84), and liver (SMR = 2.14) cancers. Standardized mortality ratios for suicide
were highest within the first 5 years of diagnosis and increased with age at
diagnosis for all sites except colon and stomach. CONCLUSIONS: Patients with
cancers of the digestive system have a higher incidence of suicide than the
general population. Suicide rates among esophageal and pancreatic cancer patients
are more than 5 times general population rates. The involvement of psychiatrists
and other mental health professionals may be a critical component of cancer care
for these high-risk patient subgroups.
PMID- 29956394
TI - Electrochemical recognition of taurine biomarker in unprocessed human plasma
samples using silver nanoparticlebased nanocomposite: A new platform for early
stage diagnosis of neurodegenerative diseases of the nervous system.
AB - The rapid and accurate determination of the level of taurine biomarker in various
tissues and body fluids can be of great interest in the early diagnosis of
several important pathologies and diseases. In the present study, an innovative
electrochemical interface for quantitation of taurine based on ternary signal
amplification strategy was fabricated. In this work, silver nanoparticles were
electrodeposited onto green and biocompatible nanocomposite containing alpha
cyclodextrin as conductive matrix. Therefore, a double layer film based on alpha
cyclodextrin and silver nanoparticles was exploited to develop a highly sensitive
electrochemical sensor for detection of taurine. Fully electrochemical
methodology was used to prepare a transducer on a glassy carbon electrode which
provided a high surface area towards sensitive detection of taurine biomarker.
The surface morphology of electrode surface was characterized by high-resolution
field emission scanning electron microscope (FE-SEM). The proposed sensing
platform provides a simple tool for taurine detection. The calibration curve for
taurine concentration was linear in 0.7 nM to 0.1 mM with low limit of
quantification of 0.7 nM. The practical analytical utility of the modified
electrode was illustrated by determination of taurine in unprocessed human plasma
samples with recovery of 90.8% to 104%.
PMID- 29956397
TI - Engineering the Future of Silk Materials through Advanced Manufacturing.
AB - Silk is a natural fiber renowned for its outstanding mechanical properties that
have enabled the manufacturing of ultralight and ultrastrong textiles. Recent
advances in silk processing and manufacturing have underpinned a re
interpretation of silk from textiles to technological materials. Here, it is
argued that silk materials-optimized by selective pressure to work in the
environment at the biotic-abiotic interface-can be harnessed by human micro- and
nanomanufacturing technology to impart new functionalities and opportunities. A
critical overview of recent progress in silk technology is presented with
emphasis on high-tech applications enabled by recent innovations in multilevel
modifications, multiscale manufacturing, and multimodal characterization of silk
materials. These advances have enabled successful demonstrations of silk
materials across several disciplines, including tissue engineering, drug
delivery, implantable medical devices, and biodissolvable/degradable devices.
PMID- 29956396
TI - PROMIS and legacy measures compared in a supportive care intervention for breast
cancer patients and caregivers: Experience from a randomized trial.
AB - OBJECTIVE: Accurate and efficient measurement of patient-reported outcomes is key
in cancer symptom management trials. The newer Patient Reported Outcomes
Measurement Information System (PROMIS) and previously developed measures of
similar conceptual content (legacy) are available to measure symptoms and
functioning. This report compares the performance of two sets of measures, PROMIS
and legacy, in a recently completed trial of a supportive care intervention that
enrolled breast cancer patients and their friend or family caregivers. METHODS:
Patient-caregiver dyads (N = 256) were randomized to either reflexology delivered
by caregivers or usual care control. Post-intervention, PROMIS and legacy
measures of symptoms and functioning were analyzed in relation to trial arm,
while adjusting for baseline values. Responsiveness of the two sets of measures
was assessed using effect sizes and P-values for the effect of trial arm on
patients' and caregivers' symptom and functioning outcomes. RESULTS: Similar
conclusions about intervention effects were found using PROMIS and legacy
measures for pain, fatigue, sleep, anxiety, physical, and social functioning.
Different conclusions were obtained for patient and caregiver depression: legacy
measures indicated the efficacy of reflexology, while PROMIS depression measure
did not. CONCLUSION: Evidence of similar responsiveness supports the use of
either set of measures for symptoms and functioning in clinical and general
populations. Differences between PROMIS and legacy measures of depression need to
be considered when choosing instruments for use in trials of supportive care
interventions and in clinical practice.
PMID- 29956395
TI - Concurrence of autophagy with apoptosis in alveolar epithelial cells contributes
to chronic pulmonary toxicity induced by methamphetamine.
AB - OBJECTIVES: Methamphetamine (MA) abuse evokes pulmonary toxicity. The aim of our
study is to investigate if autophagy is induced by MA and if autophagy-initiated
apoptosis in alveolar epithelial cells is involved in MA-induced chronic
pulmonary toxicity. MATERIALS AND METHODS: The rats in Control group and MA group
were tested by Doppler and HE staining. The alveolar epithelial cells were
treated with MA, following by western blot, RT-PCR and immunofluorescence assay.
RESULTS: Chronic exposure to MA resulted in lower growth ratio of weight and in
higher heart rate and peak blood flow velocity of the main pulmonary artery of
rats. MA induced infiltration of inflammatory cells in lungs, more compact lung
parenchyma, thickened alveolar septum and reduction in the number of alveolar
sacs. In alveolar epithelial cells, the autophagy marker LC3 and per cent of
cells containing LC3-positive autophagosome were significantly increased. MA dose
dependently suppressed the phosphorylation of mTOR to inactivate mTOR, elicited
autophagy regulatory proteins LC3 and Beclin-1, accelerated the transformation
from LC3 I to LC3 II and initiated apoptosis by decreasing Bcl-2 and increasing
Bax, Bax/Bcl-2 and cleaved Caspase 3. The above results suggest that sustained
autophagy was induced by long-term exposure to MA and that the increased Beclin-1
autophagy initiated apoptosis in alveolar epithelial cells. CONCLUSIONS:
Concurrence of autophagy with apoptosis in alveolar epithelial cells contributes
to chronic pulmonary toxicity induced by MA.
PMID- 29956398
TI - Intensity-dependent effects of aerobic training on pressure pain threshold in
overweight men: A randomized trial.
AB - PURPOSE: To investigate the chronic and acute effects of high-intensity interval
training (HIIT) and moderate-intensity continuous training (MICT) on pressure
pain thresholds (PPT) in overweight men. METHODS: Twenty-eight participants
performed stationary cycling exercise three times per week for 6 weeks.
Participants were randomly allocated to HIIT (10 * 1-min intervals at 90% peak
heart rate) or MICT (30 min at 65-75% peak heart rate). PPTs were assessed over
the rectus femoris, tibialis anterior and upper trapezius before and after the 6
week training programme (chronic effect) as well as before and after the first,
middle and final exercise sessions (acute effect). RESULTS: For chronic exercise,
PPTs increased more after MICT compared to HIIT over the rectus femoris (p =
0.009, effect size r = 0.54) and tibialis anterior (p = 0.012, r = 0.54), but not
the trapezius (p = 0.399, r = 0.29). The effect of acute exercise on PPT was more
varied and ranged from moderate hypoalgesia to moderate hyperalgesia. Overall,
however, there was no consistent change in PPT after acute exercise for HIIT or
MICT (p >= 0.231, r >= -0.31 and <=0.31). CONCLUSION: Six weeks of MICT cycling
(chronic exercise) increased PPT for the lower body, but not upper body, in
overweight men, whereas HIIT did not provide any hypoalgesic effect for chronic
exercise. The acute effect of exercise on PPT was highly variable and negligible
overall. SIGNIFICANCE: This study shows that aerobic training increases pressure
pain threshold in pain-free adults. This effect was observed only for MICT over
exercised muscles, implying intensity- and site-specific effects of exercise
training on pain threshold.
PMID- 29956399
TI - Impact of frequency of internet use on development of brain structures and verbal
intelligence: Longitudinal analyses.
AB - Excessive internet use is shown to be cross sectionally associated with lower
cognitive functioning and reduced volume of several brain areas. However, the
effects of daily internet use on the development of verbal intelligence and brain
structures have not been investigated. Here, we cross sectionally examined the
effects of the frequency of internet use on regional gray/white matter volume
(rGMV/rWMV) and verbal intelligence as well as their longitudinal changes after
3.0 +/- 0.3 (standard deviation) years in a large sample of children recruited
from the general population (mean age, 11.2 +/- 3.1 years; range, 5.7-18.4
years). Although there were no significant associations in cross sectional
analyses, a higher frequency of internet use was found to be associated with
decrease of verbal intelligence and smaller increase in rGMV and rWMV of
widespread brain areas after a few years in longitudinal analyses. These areas
involve areas related to language processing, attention and executive functions,
emotion, and reward. In conclusion, frequent internet use is directly or
indirectly associated with decrease of verbal intelligence and development to
smaller gray matter volume at later stages.
PMID- 29956401
TI - Can cancer-related cognitive impairment be considered in isolation from other
cancer-related symptoms?
PMID- 29956400
TI - Neural specialization of phonological and semantic processing in young children.
AB - This study aimed to examine early specialization of brain regions for
phonological and semantic processing of spoken language in young children. Thirty
five typically developing children aged from 5 to 6 years performed auditory
phonological (same sound judgment) and semantic (related meaning judgment) word
level tasks. Using functional magnetic resonance imaging, we examined
specialization within the language network, by conducting three levels of
analysis. First, we directly compared activation between tasks and found a
greater sound judgment as compared to meaning judgment activation in left
superior temporal gyrus (STG) and supramarginal gyrus. In contrast, greater
meaning judgment as compared to sound judgment task activation was found in left
middle temporal gyrus (MTG). Second, we examined the brain-behavior correlations
and found that phonological skill was correlated with the task difference in
activation in left superior temporal sulcus, whereas semantic skill was
correlated with the task difference in activation in left MTG. Third, we compared
between two experimental conditions within each task and found a parametric
effect in left STG for the sound judgment task, and a parametric effect in left
MTG for the meaning judgment task. The results of this study indicate that, by
the age of 5-6 years, typically developing children already show some
specialization of temporo-parietal brain regions for phonological and semantic
processes. However, there were no task differences in the left inferior frontal
gyrus suggesting that the frontal cortex may not yet be specialized in this age
range, which is consistent with the delayed maturation of the frontal cortex.
PMID- 29956402
TI - Canine meningiomas treated with three-dimensional conformal radiation therapy
require magnetic resonance imaging to avoid a geographic miss.
AB - Exact target volume definition is an essential prerequisite for modern
radiotherapy treatment planning. Contouring the gross tumor volume of brain
tumors on computed tomography (CT) images coregistered with magnetic resonance
images is standard practice in human medicine. In this retrospective study,
including only cases with an imaging diagnosis of meningioma, we hypothesized
that the gross tumor volume contoured from the contrast-enhanced magnetic
resonance imaging (MRI) (gross tumor volume-MRI) is larger when compared to the
gross tumor volume contoured using contrast-enhanced CT (gross tumor volume-CT).
A total of 22 dogs were included in the study. Interestingly, there was a
significant statistical difference between the gross tumor volume-CT and the
gross tumor volume-MRI (P = 0.001). The gross tumor volume-MRI was larger than
the gross tumor volume-CT in all, but two cases. The mean ratio between gross
tumor volume-MRI and gross tumor volume-CT was 1.43 (range 0.84-4.00). The mean
overlap between gross tumor volume-CT and gross tumor volume-MRI was 68% (range
22-86%), while a mean of 26% of the composite gross tumor volume was defined only
by MRI (range 4-76%) and a mean of 6% only by CT (range 0-22%). These findings
suggest that CT and MRI are complementary modalities in radiation planning of
meningiomas and their composite volume should be used to avoid geographical miss
of neoplastic tissue. When the MRI is not available for planning, a margin of 0.3
cm around the gross tumor volume-CT could reduce the probability of a
geographical miss. However, such numerical correction cannot be applied to the
clinical practice until it is validated in a properly designed treatment planning
study.
PMID- 29956403
TI - Increased fMRI activity correlations in autobiographical memory versus resting
states.
AB - Autobiographical memory retrieval is associated with activity of a distributed
network that is similar to the default-mode network (DMN) identified via activity
correlations measured during rest. We tested whether activity correlations could
be used to identify the autobiographical network during extended bouts of
retrieval. Global-correlativity analysis identified regions with activity
correlation differences between autobiographical-retrieval and resting states.
Increased correlations were identified for retrieval versus resting states within
a distributed network that included regions prototypical for autobiographical
memory. This network segregated into two subnetworks comprised of regions related
to memory versus cognitive control, suggesting greater functional segregation
during autobiographical retrieval than rest. DMN regions were important drivers
of these effects, with increased correlations between DMN and non-DMN regions and
segregation of the DMN into distinct subnetworks during retrieval. Thus, the
autobiographical network can be robustly identified via activity correlations and
retrieval is associated with network functional organization distinct from rest.
PMID- 29956404
TI - Determinants of slowed conduction in premature ventricular beats induced during
programmed stimulations in perfused guinea-pig heart.
AB - NEW FINDINGS: What is the central question of this study? Is the slowed
conduction upon premature ventricular activations during clinical
electrophysiological testing attributable to the prolonged activation latency, or
increased impulse propagation time, or both? What is the main finding and its
importance? Prolonged activation latency at the stimulation site is the critical
determinant of conduction slowing and associated changes in the ventricular
response intervals in premature beats initiated during phase 3 repolarization in
perfused guinea-pig heart. These relations are likely to have an effect on
arrhythmia induction and termination independently of the presence of ventricular
conduction defects or the proximity of the stimulation site to the re-entrant
circuit. ABSTRACT: During cardiac electrophysiological testing, slowed conduction
upon premature ventricular activation can limit the delivery of the closely
coupled impulses from the stimulation site to the region of tachycardia origin.
In order to examine the contributing factors, in this study, cardiac conduction
intervals and refractory periods were determined from left ventricular (LV) and
the right ventricular (RV) monophasic action potential recordings obtained in
perfused guinea-pig hearts. A premature activation induced immediately after the
termination of the refractory period was associated with conduction slowing. The
latter was primarily accounted for by the markedly increased (+54%) activation
latency at the LV stimulation site, with only negligible changes (+12%) noted in
the LV-to-RV delay. The prolonged activation latency was acting to limit the
shortest interval at which two successive action potentials can be induced in the
LV and RV chambers. The prolongation of the activation latency in premature beats
was accentuated upon an increase in the stimulating current intensity, or during
hypokalaemia. This change was related to the reduced ratio of the refractory
period to the action potential duration, which allowed extrastimulus capture to
occur earlier during phase 3 repolarization. Flecainide, a Na+ channel blocker,
prolonged both the activation latency and the LV-to-RV delay, without changing
their relative contributions to conduction slowing. In summary, these findings
suggest that the activation latency is the critical determinant of conduction
slowing and associated changes in the ventricular response intervals upon
extrastimulus application during phase 3 of the action potential.
PMID- 29956405
TI - Language network measures at rest indicate individual differences in naming
decline after anterior temporal lobe resection.
AB - While anterior temporal lobe (ATL) resection is an effective treatment for
temporal lobe epilepsy, surgery on the dominant hemisphere is associated with
variable decline in confrontation naming. Accurate prediction of naming
impairment is critical to inform clinical decision making, and while there has
been some degree of success using task-based functional MRI (fMRI) paradigms,
there remains a growing interest in the predictive utility of resting-state
connectivity as it allows for relatively shorter scans with low task demands. Our
objective was to assess the relationship between measures of preoperative resting
state connectivity and postoperative naming change in patients following left ATL
resection. We compared the resting language network connectivity of each patient
to a normative healthy control template using a novel measure called "matrix
similarity," and found that patients with more abnormal global language-network
connectivity-particularly of regions spared from surgery-showed greater
postoperative naming decline than those with normative patterns of connectivity.
When we interrogated the degree centrality of to-be-resected regions in a more
targeted approach of the pathological temporal lobe, we found that greater
functional integration of those regions with the rest of the language network at
rest was related to greater decline in naming following surgery. Finally, we
found that matrix similarity was a better predictor of postoperative outcome than
degree within to-be-resected regions, network clustering, modularity, and
language task fMRI laterality. We provide some of the first evidence that using
this novel measure, a relatively short preoperative resting scan can be exploited
to inform naming ability following ATL resection.
PMID- 29956406
TI - Influence of new hire transition workload on insomnia in nurses.
AB - AIMS: In this study, we investigated the relationship of the prevalence and
incidence of insomnia with the new hire transition workload in nurses. METHODS:
This retrospective study used the clinical diagnosis data of the entire nursing
population in Taiwan for 2005 to 2008, drawn from the National Health Insurance
Research Database. Adjusted logistic regression and Cox regression models were
used to separately analyse factors related to the prevalence and incidence of
insomnia. RESULTS: During this period, the prevalence of insomnia increased,
whereas its incidence remained stable. After adjustment for demographic variables
in the logistic regression models, the higher prevalence of insomnia was
associated with a longer employment duration and a higher new hire ratio. In the
Cox regression models, a higher incidence of insomnia was associated with a
shorter employment duration and a higher new hire ratio. Nurses with a longer
employment duration had a higher prevalence, but lower incidence, of insomnia. A
higher new hire ratio was associated with a higher prevalence and incidence of
insomnia. CONCLUSION: To mitigate the risk of insomnia, we suggest that
additional support should be provided to non-new nurses to assist them in the new
hire transition.
PMID- 29956407
TI - Removal of retained products of conception showing marked vascularity without
uterine artery embolization: Two case reports.
AB - Retained products of conception with marked vascularity can cause massive
postabortal or post-partum bleeding. Uterine artery embolization is effective for
uterus preservation but does not assure fertility preservation. Thus, the optimal
treatment for retained products of conception with marked vascularity is
uncertain. Here, we report two cases of retained products of conception with
marked vascularity: one early abortion and one hydatidiform mole, which were
successfully resolved by dilation and removal of the retained products, without
uterine artery embolization. We pretreated the cervical dilation using two or
more laminaria tents and named this technique the 'maximum laminaria procedure'.
We observed that the vascularity disappeared just after the laminaria tents were
removed, and subsequently, we could remove the retained products with minimal
bleeding, without uterine artery embolization. This protocol might become a
standard treatment for retained products of conception with marked vascularity.
PMID- 29956408
TI - Deregulation of the Notch pathway as a common road in viral carcinogenesis.
AB - The Notch pathway is a conserved signaling pathway and a form of direct cell-cell
communication related to many biological processes during development and
adulthood. Deregulation of the Notch pathway is involved in many diseases,
including cancer. Almost 20% of all cancer cases have an infectious etiology,
with viruses responsible for at least 1.5 million new cancer cases per year.
Seven groups of viruses have been classified as oncogenic: hepatitis B and C
viruses (HBV and HCV respectively), Epstein-Barr virus (EBV), Kaposi sarcoma
associated herpesvirus (KSHV), human T lymphotropic virus (HTLV-1), human
papillomavirus (HPV), and Merkel cell polyomavirus (MCPyV). These viruses share
the ability to manipulate a variety of cell pathways that are critical in
proliferation and differentiation, leading to malignant transformation. Viral
proteins interact directly or indirectly with different members of the Notch
pathway, altering their normal function. This review focuses exclusively on the
direct interactions of viral oncoproteins with Notch elements, providing a deeper
understanding of the dual behavior of the Notch pathway as activator or
suppressor of neoplasia in virus-related cancers.
PMID- 29956409
TI - Developmental competence of eggs produced by rainbow trout Doubled Haploids (DHs)
and generation of the clonal lines.
AB - Poor quality eggs produced by the fully homozygous doubled haploids (DHs) may
impair generation of clonal lines in fish species. In the present research,
gynogenetic development of rainbow trout (Oncorhynchus mykiss) was induced in
eggs originated from the DH females. Eggs were activated with the UV-irradiated
grayling (Thymallus thymallus) spermatozoa and subjected to the high hydrostatic
pressure (HHP) shock to provide diploid clonal individuals. Only two of four DH
females produced eggs that were successfully activated by the irradiated
spermatozoa and subsequently developed into the gynogenetic embryos. Survival
rates of rainbow trout from the clonal lines equalled 21.5% and 19.8% during
embryogenesis and decreased after hatching to 18.6% and 14.9%, respectively. Some
of the dead rainbow trout clones collected between hatching and swim-up stage
were emaciated and exhibited spinal deformities including scoliosis. Provided
results confirmed limited developmental competences of eggs produced by rainbow
trout DH females. Clonal rainbow trout developing in such eggs exhibited reduced
survival and increased frequency of the body abnormalities.
PMID- 29956410
TI - Nonlinear neuroplasticity corresponding to sports experience: A voxel-based
morphometry and resting-state functional connectivity study.
AB - We aimed to investigate the structural neuroplasticity associated with different
levels of sports experience and its effect on the corresponding resting-state
functional circuitry. We recruited 18 skilled baseball batters (SB), 19
intermediate baseball batters (IB), and 17 healthy controls (HC), and used
magnetic resonance imaging methods to compare their regional gray-matter volume
(GMV) and seed-based resting-state functional connectivity (rsFC). Our results
revealed that a quadratic function could better depict intergroup differences in
regional GMV than a linear function. In particular, the IB showed lower or higher
regional GMV than the other two groups. The difference in GMV in the
supplementary motor area and areas belonging to the ventral stream, including the
middle temporal gyrus and middle temporal pole, might be possibly related to
baseball-specific motor and perceptual experience, such as inhibitory action
control and pitch identification. On the other hand, the stronger rsFC seeded
from the right middle temporal pole to the default mode network, particularly in
the precuneus, in the SB and IB relative to that in the HC might be possibly
associated with the theory of mind, such as deciding whether to swing or not
against the pitcher by detecting the spatial information of pitches. In
conclusion, our three-group design enabled the capture of the unique and
transient changes that occur during the intermediate phase of expertise
development. Our findings indicated that structural and functional brain changes
do not necessarily linearly increase as a function of experience as previously
suggested by the literature.
PMID- 29956411
TI - Effects of repeated conditioning pain modulation in healthy volunteers.
AB - BACKGROUND: Conditioned pain modulation (CPM) may be impaired in chronic pain
patients compared with healthy subjects. The CPM-effect is the difference between
pain sensitivity assessments (test-stimuli) with and without a painful
conditioning stimulus. CPM has been extensively explored but effects of repeated
CPM-effects and differences between repeated CPM assessments and comparable
control conditions are less studied. METHODS: In 20 healthy men, four 5-min bouts
with a test-stimulus in the beginning and midway were applied by cuff-algometry
to the dominant leg. The 2nd test-stimulus in each bout was conditioned in
parallel by a painful cuff pressure on the contralateral leg. A control-session
was performed without conditioning. The conditioning intensity was 70% of the
pressure-pain tolerance threshold (PTT) assessed at baseline. Pain detection
threshold (PDT) was extracted from test-stimuli. CPM/Control-effects were
calculated as second minus first test-stimulus, and netCPM-effects were
calculated as the difference between CPM-effects and Control-effects. RESULTS:
Pain detection threshold increased in all four bouts (p < 0.02) compared to the
unconditioned test-stimulus and compared to the 2nd test-stimulus in bout1, bout3
and bout4 of the control-session (p < 0.04). In the control-session, the 1st test
stimulus PDT increased from bout1 to bout2, bout3 and bout4 (p < 0.03). The
netCPM-effect increased progressively over the four bouts (p = 0.03). CONCLUSION:
Conditioned pain modulation-effects were maintained over four consecutive bouts
and in the control-session repeated pain thresholds assessments habituated more
than in the CPM-session leading to an increase in netCPM-effect over the four
bouts. SIGNIFICANCE: Conditioning pain modulation can be assessed in 5-min
intervals by cuff algometry with a fixed conditioning stimulus. Without applying
conditioning stimuli the pain sensitivity of test-stimuli habituated. As a
consequence, it can be speculated that the conditioning stimulus may negate the
temporal habituation effects during repeated sessions, whereas this may not be
the case for unconditioned stimuli. Applying both conditioned and unconditioned
repeated test-stimuli may be a way to assess different parts of the pain
modulatory system, and a model for measuring a netCPM-effect, which could
indicate a balance between habituation and sensitization, is proposed.
PMID- 29956412
TI - The consequence of cerebral small vessel disease: Linking brain atrophy to motor
impairment in the elderly.
AB - In the elderly, brain structural deficits and gait disturbances due to cerebral
small vessel disease (CSVD) have been well demonstrated. The relationships among
CSVD, brain atrophy, and motor impairment, however, are far from conclusive.
Particularly, the effect of CSVD on subcortical nuclear atrophy, motor
performance of upper extremities, and associating patterns between brain atrophy
and motor impairment remains largely unknown. To address these gaps, this study
recruited 770 community-dwelling subjects (35-82 years of age), including both
CSVD and non-CSVD individuals. For each subject, four motor tests involving upper
and lower extremities were completed. High-resolution structural MRI was applied
to extract gray matter (GM) volume, white matter volume, cortical thickness,
surface area, and subcortical nuclear (caudate, putamen, pallidum, and thalamus)
volumes. The results showed worse motor performance of lower extremities but
relatively preserved performance of upper extremities in the CSVD group.
Intriguingly, there was a significant association between the worse performance
of upper extremities and atrophy of whole-brain GM and pallidum in the CSVD group
but not in the non-CSVD group. In addition, mediation analysis confirmed a
functional CSVD-to-"brain atrophy"-to-"motor impairment" pathway, that is, a
mediating role of thalamic atrophy in the CSVD effect on walking speed in the
elderly, indicating that CSVD impairs walking performance through damaging the
integrity of the thalamus in aging populations. These findings provide important
insight into the functional consequences of CSVD and highlight the importance of
evaluating upper extremities functions and exploring their brain mechanisms in
CSVD populations during aging.
PMID- 29956413
TI - Weight stigmatisation in antiobesity campaigns: The role of images.
AB - ISSUE ADDRESSED: Antiobesity campaigns may inadvertently stigmatise individuals
with obesity via the use of images that portray negative obesity stereotypes.
This study investigated the impact of images on weight stigma using mock
antiobesity campaigns featuring different types of images. METHODS: Participants
(N = 240) were randomly assigned to one of four campaign conditions:
stereotypical images, counter-stereotypical images, neutral images, or no images.
All four conditions used the same nonstigmatising message text. Participants
indicated their attitudes towards being in social situations (desired social
distance) with the target featured in the images, or individuals with obesity (no
images), rated the target or individuals with obesity on various traits, and
indicated to what extent the campaign was motivating and stigmatising. RESULTS:
Analysis of variance revealed that the stereotypical images were rated as the
most stigmatising and were also associated with higher negative and lower
positive trait ratings of the target and more desired social distance from the
target. Neutral images generally produced the least weight stigma. CONCLUSION: It
is important to consider the impact of antiobesity campaign images that depict
common obesity stereotypes. Developing, testing and disseminating nonstigmatising
campaigns is important to reduce stigma and better engage individuals with
antiobesity public health messages. SO WHAT?: Weight stigma has negative
consequences for physical and psychological health, which may undermine obesity
intervention efforts. Stereotypical images that blame individuals for their
weight reinforce obesity stigma and are likely to be in-effective in increasing
healthier behaviour and reducing obesity. The development of effective
antiobesity campaigns should be a public health priority.
PMID- 29956414
TI - Treatment effect estimators for count data models.
AB - In this paper, we consider a switching regression model with count data outcomes,
where the possible outcome differs across two alternate states and individuals
endogenously select one of the states. We assume lognormal latent heterogeneity.
Building on the switching regression model, we derive estimators of various
treatment effects: the average treatment effect, the average treatment effect on
the treated, the local average treatment effect, and the marginal treatment
effect. We illustrate an application that examines the effects of public
insurance on the number of doctor visits using the data employed by previous
studies.
PMID- 29956415
TI - Between a rock and hard place: fever and inflammation in intracerebral
hemorrhage.
PMID- 29956416
TI - Bed rest with and without hospitalization in multiple pregnancy for improving
perinatal outcomes.
PMID- 29956417
TI - Rasagiline, an inhibitor of MAO-B, decreases colonic motility through elevating
colonic dopamine content.
AB - BACKGROUND: Dopamine (DA) is a negative modulator of gut motility. Monoamine
oxidase-B (MAO-B) is an important metabolic enzyme degrading DA. Rasagiline, an
irreversible MAO-B inhibitor, is used to treat Parkinson's disease because of its
neuroprotective effect and increasing central DA. However, it is unclear whether
MAO-B exists in the colon and rasagiline increases colonic DA, thereby affecting
colonic motility. METHODS: Immunohistochemistry, western blotting, enzyme
activity assay, colonic motility recording, gut transit test, and high
performance liquid chromatography-electrochemical detection were employed in this
study. KEY RESULTS: Monoamine oxidase-B was distributed in the colonic muscular
layers including neurons and glias of rat and human. When oral treatment of rats
with rasagiline for 4 weeks, in vitro colonic motility was significantly reduced,
but it was greatly reversed by SCH-23390, an antagonist of DA D1 receptor. The
rasagiline-treated rats also manifested decreased MAO-B activity and increased DA
content in the colonic muscular layer, but no alterations were detected in the
protein expressions of D1 and D2 receptors, and MAO-A and MAO-B, as well as in
the content of 5-hydroxytryptamine and noradrenaline. Moreover, acute
administration of rasagiline did not affect the colonic motility in vitro and the
colonic DA level in rats, although MAO-B activity was significantly inhibited.
CONCLUSIONS & INFERENCES: Monoamine oxidase-B is abundant in the colonic muscular
layer including myenteric plexus of rat and human. Long-term administration of
rasagiline can increase colonic DA thereby inhibiting colonic motility,
suggesting that colonic MAO-B could be a potential drug target for colonic
dysmotility.
PMID- 29956418
TI - The "Biology-First" Hypothesis: Functional disorders may begin and end with
biology-A scoping review.
AB - While it is generally accepted that gastrointestinal infections can cause
functional disturbances in the upper and lower gastrointestinal tract-known as
postinfectious irritable bowel syndrome (PI-IBS) and functional dyspepsia (PI-FD)
it has still not been widely recognized that such an infection can also initiate
functional non-intestinal diseases, and that non-intestinal infections can
provoke both intestinal and non-intestinal functional disturbances. We conducted
a scoping review of the respective literature and-on the basis of these data
hypothesize that medically unexplained functional symptoms and syndromes
following an infection may have a biological (genetic, endocrine,
microbiological) origin, and that psychological and social factors, which may
contribute to the disease "phenotype," are secondary to this biological cause. If
this holds true, then the search for psychological and social theories and
factors to explain why one patient develops a chronic functional disorder while
another does not is-at least for postinfectious states-misleading and detracts
from exploring and identifying the true origins of these essentially biological
disorders. The biopsychosocial model may, as the term implies, always begin with
biology, also for functional (somatoform) disorders.
PMID- 29956419
TI - Escherichia coli Nissle 1917 restores epithelial permeability alterations induced
by irritable bowel syndrome mediators.
AB - BACKGROUND: Intestinal permeability is altered in a subgroup of irritable bowel
syndrome (IBS) patients and may contribute to symptom development. The aim of
this study was to evaluate the in vitro effect of the probiotic Escherichia coli
Nissle 1917 (EcN) on Caco-2 permeability alterations induced by mediators
released by IBS mucosal biopsies compared to asymptomatic controls (AC). METHODS:
Caco-2 cells were used as an in vitro model of intestinal permeability. Seven AC
and 28 well-phenotyped IBS (9 IBS-D, 8 IBS-C, and 11 IBS-M) patients were
enrolled. Mucosal mediators spontaneously released (SUP) by IBS and AC biopsies
were collected. Two concentrations of EcN (108 and 106 ) were applied to Caco-2
with or without SUP or SLIGRL (a protease-activated receptor-2 activating
peptide), tumor necrosis factor-alpha, and interferon-gamma. Paracellular
permeability was assessed by evaluating the flow of sulfonic-acid conjugated to
fluorescein through Caco-2 monolayer. KEY RESULTS: EcN 108 significantly
reinforced Caco-2 monolayer compared to cells incubated with medium alone. IBS
SUP induced a significant increase in paracellular permeability compared to AC
SUP, independently of IBS bowel habit. EcN 108 induced a significant recovery of
permeability rate compared to IBS SUP. Permeability increase induced by IBS SUP
significantly correlated with severity and frequency of abdominal pain and
abdominal distension. The co-incubation of EcN and IBS SUP abolished the above
significant correlations. CONCLUSIONS AND INFERENCES: EcN reinforces the
integrity of Caco-2 monolayer and reverts the increase of permeability induced by
mediators released by IBS biopsies. Future studies should investigate EcN
therapeutic potentials in IBS.
PMID- 29956420
TI - Effect of inducible nitric oxide synthase and neuropeptide Y in plasma and
placentas from intrahepatic cholestasis of pregnancy.
AB - AIM: To analyze inducible nitric oxide synthase (iNOS) and neuropeptide Y (NPY)
expression in maternal plasma and placentas of human with intrahepatic
cholestasis of pregnancy (ICP). METHODS: The plasma and placentas were collected
from 35 women with normal pregnancies and 33 women with ICP. Enzyme-linked
immunosorbent assays were used to investigate maternal plasma iNOS and NPY
levels. The mRNA levels and cell-specific localization of iNOS and NPY were
determined by quantitative PCR, Western Blotting and immunohistochemical analysis
in placentas. RESULTS: In human placentas, it revealed iNOS and NPY were mainly
localized in syncytiotrophoblast, cytotrophoblastin and vascular endothelium
cells using immunohistochemistry analysis. iNOS protein and mRNA expression in
ICP maternal plasma and placental tissue were significantly lower than in control
groups (P <0.01). In maternal plasma and placentas tissue from ICP patients, a
marked up-regulation of NPY protein and mRNA expression were observed (P <0.01).
CONCLUSION: iNOS and NPY may play a role in the effect of maternal cholestasis on
the placenta. The down-regulation of iNOS and up-regulation of NPY in ICP may
influence the blood flow of the utero-placental-fetal unit, which may play a
significant role in poor fetoplacental vascular perfusion, acute hypoxia and
adverse pregnancy outcomes.
PMID- 29956421
TI - Optimization of goose breast meat tenderness by rapid ultrasound treatment using
response surface methodology and artificial neural network.
AB - The aim of this study was to develop a prediction model on tenderization of goose
breast meat by response surface methodology (RSM) and artificial neural network
(ANN). The experiments were operated on the basis of a three-level, three
variable (ultrasound power, ultrasound time, and storage time) Box-Behnken
experimental design. Under RSM and ANN optimum conditions, experimental Meullenet
Owens razor shear (MORS) of meat (1862.6 g and 1869.9 g) was in reasonable
agreement with predicted one. Nevertheless, better prediction capability of ANN
was proved by higher R2 (0.996) and lower absolute average deviation = 4.257)
compared to those for RSM (0.852 and 16.534), respectively. These results
revealed that ANN was more accurate and much better than RSM model for the
optimization of tenderness of meat. The optimum conditions of ultrasound power,
ultrasound time, and storage time given by ANN were 812 W, 24.5 min and 25.7 hr,
respectively. Under the optimized condition, the cooking loss of meat
significantly decreased by ultrasound treatment compared with untreated meat.
Lower cooking loss and MORS at the optimal condition were beneficial to meet the
satisfaction of consumer and producers for meat factory.
PMID- 29956422
TI - Milk compositional changes of Laoshan goat milk from partum up to 261 days
postpartum.
AB - Despite the global increasing demand for goat milk, no data exist on the nutrient
potential of Laoshan goat milk and limited information exists on its composition
according to lactation period. In this study, the measured indicators, including
dry matter, protein, immunoglobulin, lactoferrin, fat, ash, lactose, calcium,
titratable acidity and pH from partum to 261 days postpartum of Laoshan goat
milk, followed the same law of change. There was a significant difference over
the first 5 days postpartum, after which no significant difference was observed
until days 225 postpartum. However, days 255 postpartum was like a turning point,
after which their values showed either an increasing or decreasing trend. We
concluded that the colostrum for Laoshan dairy goat was considered from days 1 to
5 postpartum and after 5 days it was as transitioned to milk when all measured
parameters were according to the normal ranges as described in this study. This
work provided updated information on the current nutritive characteristics of
Laoshan goat milk, which may be of importance in the fields of milk production,
food technology, and nutritional mutual replenishment.
PMID- 29956423
TI - Comparative study of transobturator sling with and without concomitant prolapse
surgery for female urodynamic stress incontinence.
AB - AIM: To demonstrate the clinical and urodynamic outcomes of transobturator sling
(TOT) with or without concomitant prolapse surgery for the treatment of
urodynamic stress incontinence (USI). METHODS: We recruited 143 consecutive
patients diagnosed with USI, who received outside-in TOT in a university
hospital. Preoperative and postoperative examinations were implemented using
structured urogynecological questionnaires, pelvic organ prolapse quantification
examination and urodynamic testing. Patient demographics, surgical and urodynamic
results were compared between TOT with and without concomitant prolapse surgery.
RESULTS: The mean follow-up was 30.1 months (range 12-57). Postoperative stress
urinary incontinence (SUI) occurred in 10 (7%) patients at 3 months and 10 (7%)
patients at 12 months postoperatively. There was no significant difference in
prevalence of postoperative SUI between groups of TOT only and TOT combined with
pelvic surgery. Preoperative urodynamic results demonstrated that TOT only (n =
96) had a higher maximal flow rate and a lower residual urine amount when
compared to TOT combined with pelvic surgery (n = 47). A significant decrease in
maximal urethral closure pressure (MUCP) was found in 119 patients who received
postoperative urodynamic examination. In comparison with preoperative urodynamic
data, postoperative urodynamic results showed a significant decrease in MUCP in
the TOT combined with prolapse surgery group, but no significant urodynamic
changes in the group of TOT only. CONCLUSION: Both TOT and TOT combined with
prolapse surgery can be effective in correcting SUI in patients with USI 12
months postoperatively, with significant changes in MUCP.
PMID- 29956424
TI - One MRI-compatible tDCS session attenuates ventromedial cortical perfusion when
exposed to verbal criticism: The role of perceived criticism.
AB - Transcranial direct current stimulation (tDCS) is a potential treatment strategy
for mood and anxiety disorders, but how this application may influence emotional
processes, and whether this is related to individual characteristics, is not well
understood. It has been proposed that perceived criticism (PC) may represent a
vulnerability factor for the development of such mental illnesses. To decipher
whether neural mechanisms of action of tDCS potentially differ depending on PC
status (low vs. high), we evaluated mood and brain perfusion before and after
applying MRI-compatible tDCS, and after participants were exposed to verbal
criticism in the scanner. Experimental design 30 healthy nondepressed females
were included in a sham-controlled crossover MRI-compatible tDCS study. Brain
perfusion was measured by means of arterial spin labeling (ASL) before and after
tDCS applied to the left dorsolateral prefrontal cortex (DLPFC), and after
hearing criticism. Before the experiment, all participants provided a rating of
PC in their closest environment. Principal observations at the behavioral level,
criticism made participants angrier. This was unrelated to the active or sham
stimulation. After being criticized, females scoring high on PC had significantly
decreased brain perfusion in the pregenual anterior cingulate cortex (pgACC) and
medioprefrontal cortex (mPFC), after active tDCS but not sham. The decrease in
pgACC/mPFC perfusion points to a significant impact of tDCS in brain areas
related to stress responses and self-referential processes, especially in females
scoring high on PC, which has been shown to be related to vulnerability for mood
and anxiety disorders.
PMID- 29956425
TI - Guidelines to the guidelines.
PMID- 29956426
TI - Cost and cost-effectiveness of transitioning to universal initiation of lifelong
antiretroviral therapy for all HIV-positive pregnant and breastfeeding women in
Swaziland.
AB - OBJECTIVES: To assess the costs and cost-effectiveness of transitioning from
antiretroviral therapy (ART) initiation based on CD4 cell count and WHO clinical
staging ('Option A') to universal ART ('Option B+') for all HIV-infected pregnant
and breastfeeding women in Swaziland. METHODS: We measured the total costs of
prevention of mother-to-child HIV transmission (PMTCT) service delivery at public
sector facilities with empirical cost data collected at three points in time:
once under Option A and again twice after transition to the Option B+ approach.
The cost per woman treated per month includes recurrent costs (personnel,
overheads, medication and diagnostic tests) and capital costs (buildings,
furniture, start-up costs and training). Cost-effectiveness was estimated from
the health services perspective as the cost per woman retained in care through 6
months postpartum. This analysis is nested within a larger stepped-wedge
evaluation, which demonstrated a 26% increase in maternal retention after the
transition to Option B+. RESULTS: Across the five sites, the total cost for PMTCT
during the study period (from August 2013 to October 2015, in 2015 US$) was
$868,426 for Option B+ and $680 508 for Option A. The cost per woman treated per
month was $183 for a woman on ART under Option B+, and $127 and $118 for a woman
on ART and zidovudine (AZT), respectively, under Option A. The weighted average
cost per woman treated on Option B+ was $826 compared to $525 under Option A. The
main cost drivers were the start-up costs, additional training provided and staff
time spent on PMTCT tasks for Option B+. The incremental cost-effectiveness ratio
was estimated at $912 for every additional mother retained in care through six
months postpartum. CONCLUSIONS: The cost and cost-effectiveness outcomes from
this study indicate that there is a robust economic case for pursuing the Option
B+ approach in Swaziland and similar settings such as South Africa. Furthermore,
these costs can be used to aid decision making and budgeting, for similar
settings transitioning to test and treat strategy.
PMID- 29956427
TI - Late-onset and young-onset relapsing-remitting multiple sclerosis: evidence from
a retrospective long-term follow-up study.
AB - BACKGROUND AND PURPOSE: Late-onset multiple sclerosis (MS) has a prevalence of
about 10-20% in natural history MS studies. Few data have been published about
the long-term disease trajectory in the cohort of late-onset relapsing-remitting
MS (LORRMS). The aim of this study was to identify the risk factors for reaching
an Expanded Disability Status Scale (EDSS) score of 6.0 in LORRMS (onset at >40
years of age) and young-onset relapsing-remitting MS (YORRMS) (onset between 18
and 40 years of age). METHODS: Clinical and radiological [magnetic resonance
imaging (MRI) of the brain] follow-up data were collected. Disability was
assessed by EDSS score. A Cox proportional hazards model was used to evaluate the
demographic and clinical predictors of reaching an EDSS score of 6.0 in the two
cohorts. RESULTS: A total of 671 patients with relapsing-remitting MS were
enrolled, 143 (21.3%) with LORRMS and 528 (78.7%) with YORRMS. In LORRMS, age at
onset was 47.8 +/- 5.3 (mean +/- SD) years and duration of follow-up was 120.7 +/
52.7 months. In YORRMS, age at onset was 27 +/- 2.7 years and duration of follow
up was 149.9 +/- 92.7 months. The survival curve analyses showed a higher
probability of reaching an EDSS score of 6.0 for LORRMS in a shorter time
(months) than for YORRMS (94.2 vs. 103.2 months; log-rank 8.8; P < 0.05). On MRI,
YORRMS showed more brain inflammatory features than LORRMS. In the multivariate
Cox model, age at onset [Exp(B) value, 6.5; 95% confidence interval, 1.9-22.6; P
< 0.001] and male gender [Exp(B) value, 1.7; 95% confidence interval, 1.0-2.8; P
< 0.05] were the strongest predictors of reaching an EDSS score of 6.0.
CONCLUSIONS: The male population with LORRMS reached severe disability faster
than those with YORRMS, even when YORRMS showed more brain inflammatory features
on MRI.
PMID- 29956428
TI - Patterns of occurrence of dengue and chikungunya, and spatial distribution of
mosquito vector Aedes albopictus in Swabi district, Pakistan.
AB - OBJECTIVE: Two principal vector species, Aedes aegypti and Aedes albopictus, are
known for transmission of dengue (DEN) and chikungunya (CHK) in Pakistan. We
aimed to investigate their spatial and temporal distribution. METHODS AND
RESULTS: The Maximum Entropy algorithm revealed current climatic suitability of
A. albopictus by highlighting variables contributing to its spatial distribution:
Land use cover was the most important environmental factor (63.1%) followed by
elevation-normalised difference vegetation index (10.9%), NDVI (8.5%) and annual
precipitation (7.9%). As per Normalized Difference Vegetation Index values, the
vector's presence was highly likely in areas with little vegetation such as built
up spaces or uncultivated fields, and in areas with sparse vegetation such as
grasslands and cultivated fields. Temperature variables showed differing effects
on vector ecology with annual temperature being the most important. Logistic
regression models showed that presence of the vector, build-up and distance to
roads contributed significantly to the distribution of both DEN and CHIK.
CONCLUSION: In Swabi, the mean temperatures of warmest and driest quarters are
more important in the spatial distribution of A. albopictus than mean
temperatures of the wettest and coldest quarters. Finally, disease modelling
reflects a high probability for both DEN and CHIK in the same regions over a huge
area.
PMID- 29956429
TI - Large-sized pedunculated and polypoidal angiomyofibroblastoma of the vulva: A
case report and literature review.
AB - Angiomyofibroblastoma (AMF) represents a rare, benign mesenchymal tumor with a
predilection for the vulvovaginal region, which may be misdiagnosed as aggressive
angiomyxoma (AAM). Herein, we report a case of a 20-year-old nulliparous Chinese
woman with a unique pedunculated and polypoidal mass, which had been developing
within the previous 6 months in the left labium majus, exhibiting the AAM
clinical impression but diagnosed as AMF. The mass measured 18 * 10 * 6 cm, and
contained diffuse ulcerated areas and purulent discharge. A complete excision of
the mass was performed. There was no subsequent evidence of recurrence, according
to a 13-month follow-up. As a rare benign vulvovaginal tumor, AMF can present on
patients of an early reproductive age with rapidly growing, polypoidal pattern.
The whole exon sequencing analysis revealed the genomic alterations, which may
contribute to the occurrence of AMF.
PMID- 29956430
TI - Catalytic Enantioselective Synthesis of alpha-Chiral Azaheteroaryl Ethylamines by
Asymmetric Protonation.
AB - The direct enantioselective synthesis of chiral azaheteroaryl ethylamines from
vinyl-substituted N-heterocycles and anilines is reported. A chiral phosphoric
acid (CPA) catalyst promotes dearomatizing aza-Michael addition to give a
prochiral exocyclic aryl enamine, which undergoes asymmetric protonation upon
rearomatization. The reaction accommodates a broad range of N-heterocycles,
nucleophiles, and substituents on the prochiral centre, generating the products
in high enantioselectivity. DFT studies support a facile nucleophilic addition
based on catalyst-induced LUMO lowering, with site-selective, rate-limiting,
intramolecular asymmetric proton transfer from the ion-paired prochiral
intermediate.
PMID- 29956431
TI - Validity and reliability of methods to microscopically detect and quantify
malaria parasitaemia.
AB - OBJECTIVES: The recommended microscopy method by WHO to quantify malaria
parasitaemia yields inaccurate results when individual leucocyte (WBC) counts
deviate from 8000 leucocytes/MUl. A method avoiding WBC count assumptions is the
Lambarene method (LAMBA). Thus, this study compared validity and reliability of
the LAMBA and the WHO method. METHODS: Three methods for counting parasitaemia
were applied in parallel in a blinded assessment: the LAMBA, the WHO method using
a standard factor of 8000 leucocytes/MUl ['simple WHO method' (sWHO)] and the WHO
method using measured WBC counts ['accurate WHO method' (aWHO)]. Validity was
assessed by comparing LAMBA and sWHO to the gold standard measurement of aWHO.
Reliability was ascertained by computation of intraclass correlation coefficients
(ICCs). RESULTS: 787 malaria-positive thick smears were analysed. Parasitaemia as
determined by LAMBA and sWHO increasingly deviated from aWHO the more patients'
WBCs diverged from 8000/MUl. Equations of linear regression models assessing
method deviation in percent from gold standard as function of WBC count were y =
0.00608x (95% CI -0.00693 to -0.00524) + 47.8 for LAMBA and y = -0.0125x (95% CI
0.01253 to -0.01247) + 100.1 for sWHO. Comparison of regression slopes showed
that the deviation was twice as high for sWHO as for LAMBA (P < 0.001). ICCs were
excellent (>90%) for both methods. CONCLUSIONS: The LAMBA has higher validity
than the sWHO and may therefore be preferable in resource-limited settings
without access to routine WBC-evaluation.
PMID- 29956432
TI - Warm-, hot- and pain-related neural activities depending on baseline skin
temperatures.
AB - BACKGROUND: This study investigated the characteristics of temperature-related
evoked neural activities to baseline skin temperatures on target and adjacent
sites using contact heat evoked potentials (CHEPs). METHODS: Contact heat evoked
potentials were recorded from 12 normal subjects during three stimuli: target
temperatures for "warm", "hot" and "pain" were set at 41, 46 and 51 degrees C,
respectively. The baseline temperature was separately set at 30, 35 and 40
degrees C under all conditions, and a heat pulse was delivered over the right
forearm at 41 degrees C under the warm condition, at 46 degrees C under the hot
condition and at 51 degrees C under the pain condition. RESULTS: The N2-P2
amplitude was significantly larger at the 40 degrees C baseline than at the 30
and 35 degrees C baselines during the pain condition, whereas no significant
differences were observed during the hot and warm conditions. In addition, the
effects of an interference warm stimulation to adjacent sites were examined;
however, no significant effects were observed. CONCLUSIONS: These results suggest
that the priming effects of temperature on CHEPs were only observed under the
pain condition, indicating the specificity of thermal pain, as well as a
difference in the neural mechanisms responsible for thermal noxious and innocuous
processing in human brains. SIGNIFICANCE: This study using CHEPs shows the
importance of baseline and target skin temperatures to investigate the
characteristics of temperature-related neural activities. This measure may
contribute to understanding of warm-, hot-, and pain-related neural activities in
human brains.
PMID- 29956433
TI - Rhodium-Catalyzed Intermolecular trans-Disilylation of Alkynones with Unactivated
Disilanes.
AB - Disilylation of alkynes could provide rapid entry to synthetically useful 1,2
bissilyl-alkenes, but is currently limited to activated disilanes reacting in an
intramolecular fashion. Reported herein is an efficient rhodium(I)-catalyzed
intermolecular disilylation of a wide array of alkynones with unactivated
disilanes. Importantly, this reaction produces exclusively trans-disilylation
products, selectivity that has been rarely reported. These disilylation products
were transformed into interesting pentacyclic vinyl silane ethers, among other
additional synthetic manipulations. Mechanistic studies uncovered that the
unactivated disilanes underwent facile Si-Si activation and crossover under the
reaction conditions.
PMID- 29956434
TI - Premaquick(c) versus modified Bishop score for preinduction cervical assessment
at term: A double-blind randomized trial.
AB - AIM: To test whether Premaquick biomarkers were superior to modified Bishop score
for preinduction cervical assessment at term. METHODS: A multicenter, double
blind randomized clinical trial in 151 nulliparous, cephalic presenting and
singleton pregnancies was conducted. The cervix was considered 'ripe' when at
least two out of three Premaquick biomarkers are positive or a Bishop score of
>=6. Main outcome measures were proportion of women who were administered or had
additional prostaglandin E1 analogue (PGE1) as a preinduction agent and incidence
of uterine rupture. The trial was registered in PACTR registry with approval
number PACTR201604001592143. Analysis was performed by intention-to-treat
principle. RESULTS: The need for initial PGE1 analogue (77.6% vs 98.7%, risk
ratio [RR] =0.47, 95% confidence intervals [95% CI] =0.38-0.59, P < 0.001) and
additional PGE1 analogue for cervical ripening after one insertion (44.7% vs
68.0%, RR = 0.63, 95% CI = 0.46-0.86, P = 0.004) was significantly lower in
Premaquick group. There was no significant difference in incidence of uterine
rupture (0% vs 1.4%, RR = 0.000, P = 0.324); however, the frequency of transition
to labor was statistically higher in Premaquick group (44.7% vs 22.7%, RR = 1.59,
95% CI = 1.17-2.15, P = 0.004). Interval from start of induction to any type of
delivery, need for oxytocin augmentation, vaginal delivery, number of women with
cesarean section for failed induction and number of infants admitted to neonatal
intensive care unit were similar between the two groups (P > 0.05). CONCLUSION:
Preinduction cervical assessment with Premaquick was significantly associated
with higher frequency of transition to labor and reduced need for PGE1 analogue
when compared to modified Bishop score. Further similar trials in other settings
are necessary to strengthen or refute this observation.
PMID- 29956435
TI - Superselective microcoil embolization of the vasa recta of sigmoid artery for
hemorrhaging after laparoscopic adnexectomy for corpus luteum hematoma with
severe adhesion.
AB - A 44-year-old multipara woman was referred because of the sudden onset of left
lower abdominal pain. Corpus luteum hematoma was suspected and conservatively
managed. Two days later, due to worsening of abdominal symptoms, emergency
laparoscopic surgery was performed. Severe pelvic adhesion around the left ovary
forming corpus luteum hematoma was identified. After adhesiolysis, which was
complicated by massive bleeding, left adnexectomy was performed. Hemostasis was
achieved by the coagulation of bleeding vessels, followed by spraying fibrin glue
with the placement of oxidized cellulose cotton for bleeding oozing from
dissected surface. Two hours after surgery, emergency computed tomography
performed due to the development of hemodynamic instability demonstrated
extravasation from the versa recta of the sigmoid artery. After the confirmation
of hemorrhaging, superselective catheterization to the bleeding vessel followed
by embolization by platinum microcoils were performed. Hemodynamic stability was
immediately achieved, and the postoperative course was uneventful without
manifestation of bowel ischemia.
PMID- 29956437
TI - Predictive validity of the R-URICA.
AB - OBJECTIVES: Measuring client motivation to change, and then using information
from that assessment to plan and conduct treatment, has been of great interest to
therapists. Researchers have modified a measure of motivation to change to
develop the R-URICA (Tambling & Johnson, 2012, Fam. J., 20, 59). DESIGN: This
manuscript presents the results of an exploration of the validity of the R-URICA
in a sample of individuals in couple therapy. Sample included 581 couples from a
treatment-as-usual sample of counselling clinic clients. This study presents the
results of inquiry into the ways in which scores on the R-URICA are modified over
time in therapy, an indicator of the predictive validity of the instrument.
MEASURES: R-URICA, RDAS. RESULTS: Results indicated that scores on the Action
Subscale of the R-URICA change over time, indicating that therapy positively
impacts this aspect of motivation to change. Results also suggested that the
aspects of the R-URICA are related to where couples present for couple therapy
and changes in dyadic adjustment in couple therapy. PRACTITIONER POINTS:
Practitioners should inquire about motivation to change at the outset of therapy.
Further, practitioners should be sensitive to differences in motivation to change
among families or couples as not all clients may be equally motivated.
Practitioners may wish to devote time to engagement of male partners in therapy
as males are more variable in their motivation to change and seem to impact
outcomes. Practitioners may wish to consider the use of the R-URICA as an
alternative measure of motivation to change in therapy.
PMID- 29956438
TI - Proton Spin-Lattice Relaxation in Organic Molecular Solids: Polymorphism and the
Dependence on Sample Preparation.
AB - We report solid-state nuclear magnetic resonance 1 H spin-lattice relaxation,
single-crystal X-ray diffraction, powder X-ray diffraction, field emission
scanning electron microscopy, and differential scanning calorimetry in solid
samples of 2-ethylanthracene (EA) and 2-ethylanthraquinone (EAQ) that have been
physically purified in different ways from the same commercial starting
compounds. The solid-state 1 H spin-lattice relaxation is always non-exponential
at high temperatures as expected when CH3 rotation is responsible for the
relaxation. The 1 H spin-lattice relaxation experiments are very sensitive to the
"several-molecule" (clusters) structure of these van der Waals molecular solids.
In the three differently prepared samples of EAQ, the relaxation also becomes
very non-exponential at low temperatures. This is very unusual and the decay of
the nuclear magnetization can be fitted with both a stretched exponential and a
double exponential. This unusual result correlates with the powder X-ray
diffractometry results and suggests that the anomalous relaxation is due to
crystallites of two (or more) different polymorphs (concomitant polymorphism).
PMID- 29956439
TI - Changes of leukocyte counts and expression of pro- and anti-inflammatory
cytokines in peripheral leukocytes in periparturient dairy cows with retained
fetal membranes.
AB - In dairy cows, retained fetal membranes (RFM) affect reproductive performance.
The aim of this study was to examine the leukocyte counts and the gene expression
of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), IL-8,
and IL-10 in polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear
cells (PBMCs) in cows with (n = 5) or without (n = 5) RFM during the peripartum
period. The lymphocyte counts in RFM cows were higher than those in control cows
throughout the experiment (p < .05). The expression of IL-8 in PMNs of control
cows was higher (p < .05) compared with that of RFM cows postpartum. In cows with
RFM, IL-1beta expression was higher (p < .05) in PMNs at 6 weeks postpartum
whereas the expression of IL-1beta was lower (p < .05) in PBMCs at 4 weeks
postpartum. The expression of IL-10 in PBMCs of control cows was higher (p < .05)
than that of RFM cows at 2 weeks prepartum and 4 weeks postpartum. Taken
together, our data indicate that changes of gene expression of pro- and anti
inflammatory cytokines in RFM cows might be associated with the delayed placental
separation and development of uterine inflammation in RFM cows.
PMID- 29956440
TI - The effects of recombinant human epidermal growth factor containing ointment on
wound healing and post inflammatory hyperpigmentation prevention after fractional
ablative skin resurfacing: A split-face randomized controlled study.
AB - BACKGROUND: Epidermal growth factor (EGF) is one of the important peptides in
wound healing process. The effects of EGF have been increasingly studied in
various types of ulcers. However, data on postablative laser resurfacing wound is
still limited. OBJECTIVES: To evaluate the effects of the topical EGF ointment on
wound healing process and postinflammatory hyperpigmentation (PIH) prevention
after fractional ablative laser resurfacing. MATERIALS AND METHODS: This is a
randomized split-face study. Nineteen healthy subjects were enrolled and
completed follow up protocol. Patients received single treatment of fractional
carbon dioxide laser on both cheeks. After randomization, each patient was
assigned to apply one side of the face with topical EGF ointment and another side
with petrolatum. Wound healing was evaluated by duration of scab shedding,
duration of postlaser erythema, erythema index, and transepidermal water loss on
the daily follow up period of seven days after treatment. PIH was evaluated at 2,
3 weeks and 1, 2 months follow up by photographs and melanin index. RESULTS: Most
of patients were female with Fitzpatrick skin phototype III to V. Comparing with
control (petrolatum), EGF treated side showed no significant difference in
duration of scab shedding, duration of postlaser erythema, erythema index, and
transepidermal water loss (P-value = .58, .22, .78, and .51, respectively).
Incidence of PIH was 52.6% on EGF side and 57.9% on petrolatum side, however, it
was not statistically different (P = .56). The melanin index was also not
different as well (P = .96). CONCLUSION: Topical EGF might provide significant
wound healing stimulation for chronic wound more than acute wound. Further
studies, especially in post laser wound or other cosmetic purposes are needed.
PMID- 29956441
TI - Participation in decision-making about medication: A qualitative analysis of
medication adherence.
AB - Rates of relapse in BD are high with medication nonadherence identified as an
important contributor to relapse. Psychopharmacology remains a key component to
the treatment of BD; therefore, increased understanding of medication use and
ways to promote greater adherence is essential. The aim of the study was to
identify how participants with BD experience taking prescribed medication.
Participants had BD I or BD II, were users of specialist mental health services,
aged 18-64 years, euthymic, mildly hypomanic or depressed, and on any combination
of medication. Exclusion criteria were minimal. A semistructured interview was
completed exploring patients' views of BD and factors influencing adherence based
on the Subjective Experience of Medication Interview. An inductive thematic
analysis was used to identify themes. The study participants (n = 36) had
predominantly bipolar I (78%) and were female (69%), and of New Zealand European
ethnicity (67%) with 14% Maori. The mean age was 41 years (SD: 12.0). Findings
from the thematic analysis generated three themes: Learning about the clinical
meaning of having BD, Understanding how to use medication, and Understanding what
works for me. The qualitative nature of our study limits the generalizability of
our findings to a broader population of individuals with BD. The participants
developed confidence in being in charge of their BD through a process of learning
about BD and medication and understanding what this meant for them. The findings
support greater emphasis on collaborative approaches that recognize the expertise
of the individual with BD and the clinician.
PMID- 29956442
TI - An online self-test added to colorectal cancer screening can increase the
effectiveness of familial cancer risk assessment without increasing distress.
AB - AIM: Most people who are at increased familial colorectal cancer (FCRC) risk are
not identified, despite the need for enhanced surveillance colonoscopy for
effective CRC prevention. An online self-test may enhance this identification. We
assessed whether taking an online self-test to identify increased FCRC risk
increases anxiety, distress or CRC risk perception in population-based CRC
screening. METHOD: After the precolonoscopy consultation, patients who had a
positive immunohistochemical occult faecal blood test (iFOBT+) in population
based CRC screening were invited by email to take an online self-test at home
which returned details of family history. Anxiety (STAI-DY), distress (HADS) and
CRC risk perception were assessed immediately before and after taking the online
self-test and 2 weeks later. RESULTS: Of 250 participants invited, 177 (71%)
completed the online self-test and psychological questionnaires and 153 (61%)
completed questionnaires 2 weeks later. The median age was 65 years (range 61
75). The FCRC risk was increased in 17 participants (9.6%). Of these, 12 (6.8%)
had a highly increased FCRC risk and may benefit from germline genetic testing
for Lynch syndrome. In 7 of 17 participants (40%) the self-test obtained novel
information on family history. Anxiety and distress levels were, and remained,
below a clinically relevant level. Perception of CRC risk remained unchanged.
Most participants (83%) would recommend the online self-test to others.
CONCLUSION: Of those with a iFOBT+, 9.6% had a previously unidentified
increasedFCRC risk and require an enhanced surveillance colonoscopy instead of
iFOBT. As screening for this risk did not increase anxiety or distress, and was
highly acceptable, we recommend adding the online self-test to population-based
CRC screening.
PMID- 29956436
TI - Investigating polygenic burden in age at disease onset in bipolar disorder:
Findings from an international multicentric study.
AB - OBJECTIVES: Bipolar disorder (BD) with early disease onset is associated with an
unfavorable clinical outcome and constitutes a clinically and biologically
homogenous subgroup within the heterogeneous BD spectrum. Previous studies have
found an accumulation of early age at onset (AAO) in BD families and have
therefore hypothesized that there is a larger genetic contribution to the early
onset cases than to late onset BD. To investigate the genetic background of this
subphenotype, we evaluated whether an increased polygenic burden of BD- and
schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in
BD patients. METHODS: A total of 1995 BD type 1 patients from the Consortium of
Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped
and their BD and SCZ polygenic risk scores (PRSs) were calculated using the
summary statistics of the Psychiatric Genomics Consortium as a training data set.
AAO was either separated into onset groups of clinical interest (childhood and
adolescence [<=18 years] vs adulthood [>18 years]) or considered as a continuous
measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with
regression models. RESULTS: BD- and SCZ-PRSs were not significantly associated
with age at disease onset. Results remained the same when analyses were
stratified by site of recruitment. CONCLUSIONS: The current study is the largest
conducted so far to investigate the association between the cumulative BD and SCZ
polygenic risk and AAO in BD patients. The reported negative results suggest that
such a polygenic influence, if there is any, is not large, and highlight the
importance of conducting further, larger scale studies to obtain more information
on the genetic architecture of this clinically relevant phenotype.
PMID- 29956443
TI - Phenotypic and functional characterization of tumor-derived endothelial cells
isolated from primary human hepatocellular carcinoma.
AB - AIMS: Tumor endothelial cells (TECs) have been investigated using human tumor
xenografts in mice models. In order to provide pure human TECs for the updating
of clinical anti-angiogenic cancer therapy, in the present study we established a
protocol of purification of TECs derived from clinical hepatocellular carcinoma
(HCC) and revealed the TEC features by in vitro and in vivo assays. METHODS: We
isolated TECs from fresh surgical resections of HCC by magnetic-activated cell
sorting and purified by flow cytometry sorting upon CD31 expression, referred to
as ECDHCCs. Next, we identified cultured ECDHCCs by morphology, phenotype,
genotype, and functional assays. RESULTS: The ECDHCCs appeared as Weibel-Palade
bodies under electron microscopy. They expressed endothelial markers, such as
CD31, CD105, and vascular endothelial growth factor receptor 2, and expressed the
genes that are associated with pro-angiogenesis, especially vascular endothelial
growth factor, epiregulin, and programmed cell death 10. Functionally, ECDHCCs
were capable of tube formation, wound healing, and Transwell migration in vitro.
These in vitro behaviors were validated by in vivo Matrigel plug assay in mice.
Finally, comparison of ECDHCC with the Hep-G2 liver cancer cell line showed there
was no similarity of phenotype or function between these two types of cells.
CONCLUSIONS: Tumor endothelial cells derived from human HCC can be isolated and
purified from clinical samples by flow cytometer. They have the endothelial
phenotype and morphologic features and are capable of tube formation and
migration. This study provides a useful model for researchers to study tumor
angiogenesis and screening of candidate targets.
PMID- 29956445
TI - Does winter supplementary feeding affect deer damage in a forest ecosystem? A
field test in areas with different levels of deer pressure.
AB - BACKGROUND: Supplementary feeding is a widespread but controversial practice in
game management. While many studies have been conducted on this issue, there is
limited empirical evidence on how feeding affects damage caused by wildlife. In
this context, the present study focused on the effect of artificial winter
feeding on tree damage in three mountain regions in Poland. RESULTS: The presence
of additional winter food did not increase tree damage caused by deer in any
region, as expected. Moreover, we observed that additional feeding mitigated
forest damage in one region, where the highest level of deer impact had occurred.
However, in this mountain region, the most important factor was elevation, which
was used to classify additional feeding practice as efficient or inefficient. In
the two other study regions, we did not observe any effect of supplementary
feeding. CONCLUSIONS: Additional winter supplementary feeding can reduce damage
caused by deer in forest stands, but only in areas with high deer pressure.
Moreover, feeders should be situated in locations > 600 m above sea level in our
study area. (c) 2018 Society of Chemical Industry.
PMID- 29956444
TI - Tuning the endothelial response: differential release of exocytic cargos from
Weibel-Palade bodies.
AB - : Essentials Endothelial activation initiates multiple processes, including
hemostasis and inflammation. The molecules that contribute to these processes are
co-stored in secretory granules. How can the cells control release of granule
content to allow differentiated responses? Selected agonists recruit an
exocytosis-linked actin ring to boost release of a subset of cargo. SUMMARY:
Background Endothelial cells harbor specialized storage organelles, Weibel-Palade
bodies (WPBs). Exocytosis of WPB content into the vascular lumen initiates
primary hemostasis, mediated by von Willebrand factor (VWF), and inflammation,
mediated by several proteins including P-selectin. During full fusion, secretion
of this large hemostatic protein and smaller pro-inflammatory proteins are
thought to be inextricably linked. Objective To determine if secretagogue
dependent differential release of WPB cargo occurs, and whether this is mediated
by the formation of an actomyosin ring during exocytosis. Methods We used VWF
string analysis, leukocyte rolling assays, ELISA, spinning disk confocal
microscopy, high-throughput confocal microscopy and inhibitor and siRNA
treatments to demonstrate the existence of cellular machinery that allows
differential release of WPB cargo proteins. Results Inhibition of the actomyosin
ring differentially effects two processes regulated by WPB exocytosis; it
perturbs VWF string formation but has no effect on leukocyte rolling. The
efficiency of ring recruitment correlates with VWF release; the ratio of release
of VWF to small cargoes decreases when ring recruitment is inhibited. The
recruitment of the actin ring is time dependent (fusion events occurring directly
after stimulation are less likely to initiate hemostasis than later events) and
is activated by protein kinase C (PKC) isoforms. Conclusions Secretagogues
differentially recruit the actomyosin ring, thus demonstrating one mechanism by
which the prothrombotic effect of endothelial activation can be modulated. This
potentially limits thrombosis whilst permitting a normal inflammatory response.
These results have implications for the assessment of WPB fusion, cargo-content
release and the treatment of patients with von Willebrand disease.
PMID- 29956446
TI - Securely collecting multidimensional health information from patients with
rheumatoid arthritis using smart device technology: Beneficial effect for
physicians and patients.
AB - AIM: A challenge to the medical care of patients with rheumatoid arthritis (RA)
is the management of the wide variety of information, including medication
history and disease status, obtained from multiple sources to inform treatment
decisions. To address this important clinical issue, we developed a data
management system, based on smart device technology, and evaluated the benefit of
this information to medical experts in helping them to form an impression of
patients' health and disease, and treatment status before examination. METHODS:
Fifty-seven patients with RA input relevant information about their condition and
responses to a self-report health assessment questionnaire into a smart device
template before their scheduled examination. The efficacy of the system was
assessed as a decrease in examination time at each visit, and the correlation
between the self-reported Multi-Dimensional Health Assessment Questionnaire and
the 28-joint Disease Activity Score 28-joint count erythrocyte sedimentation rate
(DAS28-ESR), which was used as a gold standard. RESULTS: Examination duration was
reduced in most patients at each visit. During the study, there were no
limitations for patients with poor eyesight or severe arthropathy in using the
system. In fact, the majority of patients found the smart technology to be easier
to use than hand-written questionnaires and health forms, regardless of age and
disease activity. CONCLUSIONS: Our findings support the use of smart technology
to provide accurate patient-specific data and to streamline the process of
medical care for patients with RA.
PMID- 29956447
TI - Continuous dynamic gesture spotting algorithm based on Dempster-Shafer Theory in
the augmented reality human computer interaction.
AB - BACKGROUND: Human-computer interaction (HCI) is an important feature of augmented
reality (AR) technology. The naturalness is the inevitable trend of HCI. Gesture
is the most natural and frequently used body auxiliary interaction mode in daily
interactions except for language. However, there are often meaningless,
subconscious gesture intervals between the two adjacent dynamic gestures. So,
continuous dynamic gesture spotting is the premise and basis of dynamic gesture
recognition, but there is no mature and unified algorithm to solve this problem.
AIMS: In order to realize the natural HCI based on gesture recognition entirely,
a general AR application development platform is presented in this paper.
METHODS: According to the position and pose tracking data of the user's hand, the
dynamic gesture spotting algorithm based on evidence theory is proposed. Firstly,
Through analysis of the speed change of hand motion during the dynamic gestures,
three knowledge rules are summed up. Then, accurate dynamic gesture spotting is
realized with the application of evidence reasoning. Moreover, this algorithm
first detects the starting point of gesture in the rising trend of hand motion
speed, eliminates the delay between spotting and recognition, and thus ensures
real-time performance. Finally, the algorithm is verified in several AR
applications developed on the platform. RESULTS: There are two main experimental
results. First, there are six users participating in the dynamic gesture spotting
experiment, and the gesture spotting accuracy can meet the demand. Second, The
accuracy of recognition after spotting is higher than that of the simultaneous
recognition and spotting. CONCLUSION: So, It can be concluded that the proposed
continuous dynamic gesture spotting algorithm based on Dempster-Shafer theory can
extract almost all the effective dynamic gestures in the HCI of our AR platform,
and on this basis, it can effectively improve the accuracy of the subsequent
dynamic gesture recognition.
PMID- 29956449
TI - Evaluation of dependent variable, time effect, covariates, and covariation
structure in concentration-QTc modeling: A simulation study.
AB - The revised ICH E14 Question and Answer (R3) document issued in December 2015
enables pharmaceutical companies to use concentration-QTc (C-QTc) modeling as the
primary analysis for assessing QTc prolongation risk of new drugs. A new approach
by including the time effect into the current C-QTc model is introduced. Through
a simulation study, we evaluated performances of different C-QTc modeling with
different dependent variables, covariates, and covariance structures. This
simulation study shows that C-QTc models with DeltaQTc being dependent variable
without time effect inflate false negative rate and that fitting C-QTc models
with different dependent variables, covariates, and covariance structures impacts
the control of false negative and false positive rates. Appropriate C-QTc
modeling strategies with good control of false negative rate and false positive
rate are recommended.
PMID- 29956448
TI - Tracking neural crest cell cycle progression in vivo.
AB - Analysis of cell cycle entry/exit and progression can provide fundamental
insights into stem cell propagation, maintenance, and differentiation. The neural
crest is a unique stem cell population in vertebrate embryos that undergoes long
distance collective migration and differentiation into a wide variety of
derivatives. Using traditional techniques such as immunohistochemistry to track
cell cycle changes in such a dynamic population is challenging, as static time
points provide an incomplete spatiotemporal picture. In contrast, the
fluorescent, ubiquitination-based cell cycle indicator (Fucci) system provides in
vivo readouts of cell cycle progression and has been previously adapted for use
in zebrafish. The most commonly used Fucci systems are ubiquitously expressed,
making tracking of a specific cell population challenging. Therefore, we
generated a transgenic zebrafish line, Tg(-4.9sox10:mAG-gmnn(1/100)-2A-mCherry
cdt1(1/190)), in which the Fucci system is specifically expressed in delaminating
and migrating neural crest cells. Here, we demonstrate validation of this new
tool and its use in live high-resolution tracking of cell cycle progression in
the neural crest and derivative populations.
PMID- 29956450
TI - Design, synthesis, and insecticidal activity evaluation of novel 4-(N, N
diarylmethylamines)furan-2(5H)-one derivatives as potential acetylcholine
receptor insecticides.
AB - BACKGROUND: Flupyradifurone is a member of a novel class of insecticides that
possess excellent insecticidal activities. Halogen-containing phenyl groups are
important and indispensable structural components of many pesticides. However,
replacement of the difluoromethyl group of flupyradifurone with halogen
containing phenyl groups has not been reported. Hence, a series of novel
butenolide derivatives containing phenyl groups were synthesized and bioassayed
to discover novel compounds with excellent insecticidal activities. RESULTS: Some
target molecules exhibited good insecticidal activities against Aphis craccivora.
Among the title compounds, 4cc showed the best insecticidal activities with an
50% lethal concentration (LC50 ) value of 1.72 MUg mL-1 , which is superior to
that of pymetrozine (LC50 = 6.86 MUg mL-1 ). Molecular docking indicated that
4cc lacks oxidative metabolism by CYP6CM1 and metabolic resistance with
imidacloprid. Furthermore, label-free quantitative proteomic analysis indicated
that 4cc may be a potential acetylcholine receptor insecticide that acts on the
nicotinic acetylcholine receptor. Compound 4cc also decreased the capability for
oxidative metabolism, which further supported the molecular docking results.
CONCLUSION: This work can be used to further investigate the mechanism underlying
the insecticidal activity of butenolide derivatives and develop potential novel
butenolide insecticides. (c) 2018 Society of Chemical Industry.
PMID- 29956452
TI - Sex differences in brain structure among adolescents with bipolar disorder.
AB - OBJECTIVES: Bipolar disorder (BD) is twice as prevalent amongst female as amongst
male adolescents. Thus far, little is known regarding the neurostructural
substrates underlying this disparity. We therefore examined sex differences in
neurostructural magnetic resonane imaging (MRI) phenotypes amongst adolescents
with BD. METHODS: T1-weighted structural MRI was acquired from 44 BD (25 female
[F] and 19 male [M]) and 58 (28 F and 30 M) healthy control (HC) adolescents (13
21 years old). Whole-brain and region-of-interest (ROI) analyses examined
structural volume and cortical thickness using FreeSurfer. ROIs included the
ventrolateral prefrontal cortex (vlPFC), anterior cingulate cortex (ACC),
amygdala and hippocampus. General linear models evaluated sex-by-diagnosis
interactions, controlling for age and intracranial volume. RESULTS: Whole-brain
analysis revealed sex-by-diagnosis interactions in the left supramarginal gyrus
(SMG) (P = .02, eta2 = 0.02) and right inferior parietal lobule (IPL) volumes (P
= .04, eta2 = 0.01). Sex differences in HCs were found in the SMG (M > F) and
IPL (F > M). In BD, sex differences were reversed and of smaller magnitude in the
SMG (M < F) and of greater magnitude in the IPL (F > M), driven by trends towards
smaller SMG and IPL in BD vs HC male participants (P = .05 and .14). Whole-brain
analyses for cortical thickness, and ROI analyses for volume and cortical
thickness, were not significant. CONCLUSIONS: Normative sex differences may be
disrupted in adolescent BD in the SMG and IPL, heteromodal association network
hubs responsible for higher order integration of cognitive and emotional
processing. Unexpectedly, these findings may inform our understanding of aberrant
brain structure in adolescent BD male patients, rather than female patients.
Future work should focus on replication, as well as the impact of puberty status
and sex hormones on measures of brain structure and function.
PMID- 29956451
TI - The family of 14-3-3 proteins and specifically 14-3-3sigma are up-regulated
during the development of renal pathologies.
AB - Chronic kidney disease, the end result of most renal and some systemic diseases,
is a common condition where renal function is compromised due to fibrosis. During
renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic
reticulum (ER) is up-regulated in tubular epithelial cells (TECs) both in vitro
and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led
to the identification of the family of 14-3-3 proteins as key proteins
overexpressed as well. Furthermore, an increased expression in the majority of 14
3-3 family members was observed in 3 different animal models of renal
pathologies: the unilateral ureteric obstruction, the nephrotoxic serum
administration and the ischaemia-reperfusion. In all these models, the 14-3
3sigma isoform (also known as stratifin) was predominantly overexpressed. As in
all these models ischaemia is a common denominator, we showed that the ischaemia
induced transcription factor HIF1alpha is specifically associated with the
promoter region of the 14-3-3sigma gene. Finally, we evaluated the expression of
the family of 14-3-3 proteins and specifically 14-3-3sigma in biopsies from IgA
nephropathy and membranous nephropathy patients. These results propose an
involvement of 14-3-3sigma in renal pathology and provide evidence for the first
time that hypoxia may be responsible for its altered expression.
PMID- 29956453
TI - Decision-making in drug development using a composite definition of success.
AB - Evidence-based quantitative methodologies have been proposed to inform decision
making in drug development, such as metrics to make go/no-go decisions or
predictions of success, identified with statistical significance of future
clinical trials. While these methodologies appropriately address some critical
questions on the potential of a drug, they either consider the past evidence
without predicting the outcome of the future trials or focus only on efficacy,
failing to account for the multifaceted aspects of a successful drug development.
As quantitative benefit-risk assessments could enhance decision-making, we
propose a more comprehensive approach using a composite definition of success
based not only on the statistical significance of the treatment effect on the
primary endpoint but also on its clinical relevance and on a favorable benefit
risk balance in the next pivotal studies. For one drug, we can thus study several
development strategies before starting the pivotal trials by comparing their
predictive probability of success. The predictions are based on the available
evidence from the previous trials, to which new hypotheses on the future
development could be added. The resulting predictive probability of composite
success provides a useful summary to support the discussions of the decision
makers. We present a fictive, but realistic, example in major depressive disorder
inspired by a real decision-making case.
PMID- 29956454
TI - Automated data mining of a plan-check database and example application.
AB - PURPOSE: The aim of this work was to present the development and example
application of an automated data mining software platform that preforms bulk
analysis of results and patient data passing through the 3D plan and delivery QA
system, Mobius3D. METHODS: Python, matlab, and Java were used to create an
interface that reads JavaScript Object Notation (JSON) created for every approved
Mobius3D pre-treatment plan-check. The aforementioned JSON files contain all the
information for every pre-treatment QA check performed by Mobius3D, including all
3D dose, CT, structure set information, as well as all plan information and
patient demographics. Two Graphical User Interfaces (GUIs) were created, the
first is called Mobius3D-Database (M3D-DB) and presents the check results in both
filterable tabular and graphical form. These data are presented for all patients
and includes mean dose differences, 90% coverage, 3D gamma pass rate percentages,
treatment sites, machine, beam energy, Multi-Leaf Collimator (MLC) mode,
treatment planning system (TPS), plan names, approvers, dates and times. Group
statistics and statistical process control levels are then calculated based on
filter settings. The second GUI, called Mobius3D organ at risk (M3DOAR), analyzes
dose-volume histogram data for all patients and all Organs-at-Risk (OAR). The
design of the software is such that all treatment parameters and treatment site
information are able to be filtered and sorted with the results, plots, and
statistics updated. RESULTS: The M3D-DB software can summarize and filter large
numbers of plan-checks from Mobius3D. The M3DOAR software is also able to analyze
large amounts of dose-volume data for patient groups which may prove useful in
clinical trials, where OAR doses for large numbers of patients can be compared
and correlated. Target DVHs can also be analyzed en mass. CONCLUSIONS: This work
demonstrates a method to extract the large amount of treatment data for every
patient that is stored by Mobius3D but not easily accessible. With scripting, it
is possible to mine this data for research and clinical trials as well as patient
and TPS QA.
PMID- 29956455
TI - Survivorship care for early-stage colorectal cancer: a national survey of general
surgeons and colorectal surgeons.
AB - AIM: Few data are available on the optimal long-term care of early-stage
colorectal cancer survivors, termed survivorship care. We aimed to investigate
current practice in the management of patients following treatment for early
stage colorectal cancer. METHOD: We performed an internet survey of members of
the American Society for Colon and Rectal Surgeons about several aspects of long
term care, including allocation of clinician responsibility, challenges with
transitions to primary care physicians (PCPs), long-term care plan provision and
recommended surgical follow-up duration. RESULTS: Overall, 251 surgeons
responded. Surgeons reported taking primary responsibility for managing adverse
surgical effects (93.2%) and surveillance testing (imaging and laboratories
68.6%, endoscopy 82.4%). Barriers to PCP handoffs included patient preference for
surgical follow-up (endorsed by 76.6%) and inadequate communication with PCPs
(endorsed by 36.9%). Approximately one-third of surgeons routinely provide
survivorship care plans to PCPs; surgeons who received formal survivorship
training were more likely to do so compared to those without such training (OR
3.29, 95% CI 1.57, 6.92). Although only 20.4% of surgeons follow their patients
beyond 5 years, individuals in practice longer were more likely to continue long
term follow-up than those with <= 10 years of experience. CONCLUSIONS: This is
the largest survey of surgeons regarding long-term management for early-stage
colorectal cancer and highlights the potential for improved coordination with
PCPs and increased implementation of survivorship care plans.
PMID- 29956456
TI - The relation of atypical antipsychotic use and stress with weight in individuals
at clinical high risk for psychosis.
AB - Atypical antipsychotics (AT) and stress are related to weight gain in individuals
with severe mental illness. This cross-sectional study examines AT use, stressful
life events, and baseline weight in a sample of youth at clinical high risk for
psychosis. Results showed that dependent and desirable life events moderated the
relationship between AT use and weight after controlling for demographic factors
and selective serotonin reuptake inhibitor antidepressant (AD) use. The relation
of AD and weight was explored as a secondary analysis and showed no relation
between AD use and weight. Further, stress did not moderate the relationship
between AD medication and weight after controlling for antipsychotic use. Results
suggest that stress exposure may exacerbate the relationship between ATs and
increased weight in clinical high-risk populations. Findings have implications
for the development of interventions to address psychosocial factors that worsen
or buffer the adverse effects of antipsychotic medication on weight.
PMID- 29956457
TI - Lipopolysaccharide enhances ADAR2 which drives Hirschsprung's disease by
impairing miR-142-3p biogenesis.
AB - Researches over the past decade suggest that lipopolysaccharide is a dominant
driver of gastrointestinal motility and could damage the enteric neuron of rat or
porcine. However, it remains poorly defined whether LPS participates in
Hirschsprung's disease (HSCR). Here, we discovered that LPS increased in HSCR
tissues. Furthermore, LPS treatment suppressed the proliferation and
differentiation of neural precursor cells (NPCs) or proliferation and migration
of human 293T cells. ADAR2 (adenosine deaminase acting on RNA2)-mediated post
transcriptional adenosine-to-inosine RNA editing promotes cancer progression. We
show that increased LPS activates ADAR2 and subsequently regulates the A-to-I RNA
editing which suppresses the miR-142 expression. RNA sequencing combined with qRT
PCR suggested that ADAR2 restrain cell migration and proliferation via pri-miR
142 editing and STAU1 up-regulation. In conclusion, the findings illustrate that
LPS participates in HSCR through the LPS-ADAR2-miR-142-STAU1 axis.
PMID- 29956459
TI - Genetic interaction between DNA replication and the Notch signaling pathway.
AB - The Notch pathway is a widely conserved cell signaling system found in most
metazoans. In Caenorhabditis elegans, GLP-1/Notch signaling is required for
developmental cell fate decisions in multiple contexts. A recent report provides
a potential link between DNA replication and Notch-dependent proliferation in the
C. elegans germline.
PMID- 29956458
TI - Determinants of dietary practices during pregnancy: A longitudinal qualitative
study in Niger.
AB - Undernutrition is associated with maternal morbidity and poor pregnancy outcomes.
This qualitative study seeks to understand the multilevel factors influencing
maternal dietary practices in Niger, including the impact of pregnancy illnesses
on diet. Criterion-based, purposive sampling was used to select pregnant women
and household members from 24 villages in a rural district of the Maradi Region
in south-central Niger. Semistructured interviews (n = 153) and focus group
discussions (n = 38) explored 4 primary themes: (a) perceptions of ideal diet
during pregnancy, (b) barriers to consuming the ideal diet, (c) coping strategies
including dietary responses related to pregnancy illnesses, and (d) changes in
perceptions from early to late pregnancy. Longitudinal data collection allowed
for repeated interviews of pregnant women to document changes in dietary
practices throughout pregnancy. Transcripts were coded using an inductive
approach informed by grounded theory methodology. Participants categorized foods
into 4 primary dietary taxonomies when discussing ideal maternal diets but cited
constraints related to accessibility and availability impeding routine
consumption of these foods. Perceptions of "modern," urban foods as healthy,
coupled with key structural barriers such as food costs, were identified.
Maternal morbidity influenced food consumption, as women reported reducing food
intake early in pregnancy in response to illness episodes. Although awareness of
optimal foods for supporting healthy pregnancies was moderately high, some
misconceptions were observed and multilevel barriers to food security restricted
opportunities for consuming these foods. Nutrition-specific and nutrition
sensitive interventions could improve access and availability of acceptable foods
for supporting increased dietary intake during pregnancy.
PMID- 29956460
TI - Mechanisms of enhanced antiglioma efficacy of polysorbate 80-modified paclitaxel
loaded PLGA nanoparticles by focused ultrasound.
AB - The presence of blood-brain barrier (BBB) greatly limits the availability of
drugs and their efficacy against glioma. Focused ultrasound (FUS) can induce
transient and local BBB opening for enhanced drug delivery. Here, we developed
polysorbate 80-modified paclitaxel-loaded PLGA nanoparticles (PS-80-PTX-NPs,
PPNP) and examined the enhanced local delivery into the brain for glioma
treatment by combining with FUS. Our result showed PPNP had good stability, fast
drug release rate and significant toxicity to glioma cells. Combined with FUS,
PPNP showed a stronger BBB permeation efficiency both in the in vitro and in vivo
BBB models. Mechanism studies revealed the disrupted tight junction, reduced P
glycoprotein expression and ApoE-dependent PS-80 permeation collectively
contribute to the enhanced drug delivery, resulting in significantly stronger
antitumour efficacy and longer survival time in the tumour-bearing mice. Our
study provided a new strategy to efficiently and locally deliver drugs into the
brain to treat glioma.
PMID- 29956462
TI - Determination of inorganic cations in biological fluids using a hybrid capillary
electrophoresis device coupled with contactless conductivity detection.
AB - We describe the assembly of a hybrid electrophoresis device that contains fused
silica capillaries interconnected to a microfabricated interface in a cross
format for the determination of inorganic cations in biological samples. The
sample transport in the proposed hybrid device was performed under gated
injection mode and the separations were monitored with a capacitively coupled
contactless conductivity detector. The capillary extremities were inserted into
polypropylene tubes to create solution reservoirs. Sensing electrodes were
produced using stainless-steel hypodermic needles previously cut with 2.0 mm
length. The running composition and injection time were optimized and the best
results were found using 50 mmol/L lactic acid, 20 mmol/L histidine and 3 mmol/L
18-crown-6 ether, and an electrokinetic injection time of 15 s. The separation of
six inorganic cations was achieved with baseline resolution, and efficiencies
were between 9.1 * 103 and 5.4 * 104 plates/m. The proposed hybrid device was
explored for determining the concentration levels of inorganic cations in urine,
saliva, and tear samples, employing Li+ as an internal standard. The achieved
results were in good agreement with the data reported in the literature. The
reliability of the proposed method ranged from 93 to 98%, thus suggesting
satisfactory accuracy for bioanalytical applications.
PMID- 29956464
TI - On top: Another great year for Acta Physiologica.
PMID- 29956463
TI - Independent evaluation of the effectiveness of IsoCal in improving image center
accuracy on Varian TrueBeam and Clinac machines.
AB - Modern medical linear accelerators (linacs) are often equipped with image
guidance systems that are capable of megavolt (MV), kilovolt (kV), planar, or
volumetric imaging. On Varian TrueBeam linacs, the isocenter accuracies of the
imaging systems are calibrated with a procedure named IsoCal. On Clinac series
linacs from Varian, installation of IsoCal is optional and the effects of IsoCal
on the imaging systems can be turned on or off after the IsoCal procedure is
performed. In this study, we report on the effectiveness of IsoCal in improving
the coincidence of the image centers with the radiation isocenter, using an
independent Winston-Lutz (WL) method to locate the radiation isocenter. A ball
bearing phantom was imaged with 2D MV, 2D kV, and cone beam computed radiography
systems on two TrueBeam and two Clinac machines. Using the same phantom, digital
WL tests with 16 combinations of gantry and collimator angles were performed to
locate the radiation isocenter. The offsets between the IsoCal-calibrated image
centers and the WL radiation isocenter were found to be within 0.4 mm on the four
linacs in this study. When IsoCal was turned off, the maximal offsets of the
image centers were greater than 1.0 mm on the two Clinac machines. The method
developed in this study can be used as a vendor-independent quality assurance
tool to assess the isocentricity of the image centers and radiation central axes.
PMID- 29956465
TI - Vegetating erosive cutaneous lesions and pyogenic granuloma in the course of
mucous membrane pemphigoid: a case report and review of literature.
AB - Mucous membrane pemphigoid (MMP) is a group of chronic autoimmune sub-epithelial
blistering disorders, which mostly affect the oral mucosa and the conjunctiva.
MMP is very diverse in terms of both the clinical and immunological features (IgG
and IgA autoantibodies may react with different antigens). MMP can be induced by
infections and medication, including ophthalmologic medication, which may lead to
the development of eye lesions. In contrast, a vegetating variant of MMP is
extremely rare. Here, we report an MMP case that demonstrated unusual clinical
features, that is, pyogenic granulomas on the conjunctivae and extensive
vegetating erosions on the skin of intertriginous regions. All these lesions were
considered to be induced by unconventional medication containing arsenic.
PMID- 29956467
TI - Surgical treatment and strategy in patients with multiple pressure sores.
AB - Pressure sores remain a common health problem, particularly among the physically
limited or bedridden elderly, and can cause significant morbidity and mortality.
This study aimed to present our surgical treatment and strategy for patients with
multiple pressure sores. Between January 2010 and December 2016, 18 patients were
enrolled. After adequate debridement, pressure sores were managed based on our
treatment protocol. Patients' age, aetiology, defect size and location, flap
reconstruction, outcome, and follow-up period were reviewed. A total of 10 men
and 8 women (average age, 82.3 years) with a mean follow-up period of 28.3 months
(6-72 months) were included. The mean defect area was 63.7 cm2 . The most common
aetiology of the bedridden state was cerebrovascular accident (38.89%), and the
most frequent sores were trochanteric pressure sores (53.57%). The average
operative time and blood loss were 105.5 minutes and 100.8 mL, respectively. No
haemodynamic variation or blood transfusion was noted during the surgery. The
complication rate for each sore was 10.7%, including late recurrence. In
conclusion, treating pressure ulcers requires careful patient education,
intensive multidisciplinary optimisation, and meticulous wound care, and our
treatment protocol ensures a shorter surgery time, less bleeding, and low
complication rate.
PMID- 29956466
TI - Nanofiber-Based Multi-Tubular Conduits with a Honeycomb Structure for Potential
Application in Peripheral Nerve Repair.
AB - Peripheral nerve injury is a large-scale problem and it is a great challenge to
repair the long lesion in a thick nerve. The design of a multi-tubular conduit
with a honeycomb structure by mimicking the anatomy of a peripheral nerve for the
potential repair of large defects in thick nerves has been reported. A bilayer
mat of electrospun nanofibers is rolled up to form a single tube, with the inner
and outer layers comprised aligned and random nanofibers, respectively. Seven
such tubes are then assembled into a hexagonal array and encased within the lumen
of a larger tube to form the multi-tubular conduit. By introducing an adhesive to
the regions between the tubes, the conduit is robust enough for handling during
surgery. The seeded bone marrow stem cells (BMSCs) are able to proliferate in all
the tubes with even circumferential and longitudinal distributions. Under
chemical induction, the BMSCs are transdifferentiated into Schwann-like cells in
all the tubes. While the cellular version holds great promise for peripheral
nerve repair, the multi-tubular conduit can also be used to investigate the
fundamental aspects involved in the development of peripheral nervous system and
migration of cells.
PMID- 29956468
TI - Lipoedema is not lymphoedema: A review of current literature.
AB - Lipoedema is a rare painful disorder of the adipose tissue. It essentially
affects females and is often misdiagnosed as lymphoedema or obesity. It is
globally misdiagnosed or underdiagnosed, and the literature is lacking
appropriate guidance to assist clinicians towards this diagnosis. However, the
need to recognise this disorder as a unique entity has important implications to
establish proper treatment and, therefore, its tremendous effect on patients.
Early diagnosis and treatment can turn these patients' lives upside down. The aim
of this review is to focus on the clinical guidance, differential diagnosis, and
management strategies. In addition, other aspects of lipoedema, including
epidemiology and pathogenesis, are also being discussed here. Lipoedema is
distinct from obesity and distinct from lymphoedema, although it might progress
to involve the venous and lymphatic system (venolipedema or lympholipedema or
both). Late diagnosis can leave the patient debilitated. Management of lipoedema
includes weight loss, control of oedema, complex decongestive physiotherapy,
liposuction, and laser-assisted lipolysis. However; there are increasing reports
on tumescent liposuction as the preferred surgical option with long-lasting
results. The role of more randomised controlled studies to further explore the
management of this clinical entity remains promising.
PMID- 29956461
TI - The regulatory role of microRNAs in angiogenesis-related diseases.
AB - MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a
post-transcriptional level via either the degradation or translational repression
of a target mRNA. They play an irreplaceable role in angiogenesis by regulating
the proliferation, differentiation, apoptosis, migration and tube formation of
angiogenesis-related cells, which are indispensable for multitudinous
physiological and pathological processes, especially for the occurrence and
development of vascular diseases. Imbalance between the regulation of miRNAs and
angiogenesis may cause many diseases such as cancer, cardiovascular disease,
aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic
microvascular complication. Therefore, it is important to explore the essential
role of miRNAs in angiogenesis, which might help to uncover new and effective
therapeutic strategies for vascular diseases. This review focuses on the
interactions between miRNAs and angiogenesis, and miRNA-based biomarkers in the
diagnosis, treatment and prognosis of angiogenesis-related diseases, providing an
update on the understanding of the clinical value of miRNAs in targeting
angiogenesis.
PMID- 29956469
TI - New application of purse string suture in skin cancer surgery.
AB - Closure of large wounds may require full-thickness skin grafts, but their use is
burdened by donor tissue availability and morbidity; the use of the purse string
technique is an elegant way to overcome this problem. The study highlights the
gain in terms of graft donor site morbidity and oncological radicality. The study
included a group of 47 patients who underwent surgical excision for skin cancer
and whose wounds were covered using a purse string suture and a skin graft.
Radius of the defect left was measured after the lesion's excision and after the
purse string suture. Thereafter, the difference between the initial defect area
and the area after purse string suture was calculated. Initial defects ranged
from 3.85 to 61.5 cm2 . After skin graft, the purse string suture ranged between
2.2 and 40 cm2 (mean area = 14 cm2 ). Gained area before the graft measured from
1.3 to 21.5 cm2 (mean gained area = 7.1 cm2 ). Average reduction was 33%. The
technique allows a reduction of the size of the area to be grafted and the skin
graft donor area, thus increasing the possibility of the feasibility of full
thickness grafts. In addition, it allows an optimal observation both of the area
of tumour excision and margins during follow-up controls.
PMID- 29956470
TI - Determination of variation in complete blood cell count parameters with storage
conditions in a laboratory hub system, rural Eastern Uganda.
PMID- 29956471
TI - An intra-individual surgical wound comparison shows that octenidine-based
hydrogel wound dressing ameliorates scar appearance following abdominoplasty.
AB - Hypertrophic scar formation because of surgical procedures is associated with
higher levels of pain, a lower quality of life, and poor cosmetic outcome and
requires more resources in follow-up management. An octenidine-based hydrogel has
been shown to modulate immunological function in an in vitro wound model,
suggesting an improved scar formation. In this prospective, randomised, observer
blinded, and intra-patient-controlled study, 45 patients who underwent
abdominoplasty or mastectomy with transverse rectus abdominis muscle (TRAM) flap
reconstruction were given both a standard postoperative wound dressing on one
wound side and an octenidine-based hydrogel with transparent film dressing,
covered with standard postoperative dressing on the other side. Four instances of
hypertrophia were reported in the gel side versus 12 in the standard dressing
side. Visual Analogue Scale (VAS) pain scores taken during postoperative dressing
changes showed reduced scores on the gel side at all time points. Vancouver Scar
Scale (VSS) scores showed improvement in the gel side at 3, 6, and 12 months
postoperatively. Skin distensibility measured using a cutometer showed
significantly improved measures in gel-treated wounds, similar to measures of
healthy skin. Trans-epidermal water loss (TEWL), measured using a tewameter,
showed improved values on the gel side soon after surgery, with both the control
and the gel side normalising after approximately 6 months. The octenidine-based
wound dressing demonstrates improved wound healing associated with a lower
incidence of hypertrophic scar formation.
PMID- 29956472
TI - Thrombopoietin receptor agonists in hereditary thrombocytopenias.
AB - Hereditary thrombocytopenias (HTPs) constitute a heterogeneous group of diseases
characterized by a reduction in platelet count and a potential bleeding risk. As
a result of advances in diagnostic methods, HTPs are increasingly being
identified, and appear to be less rare than previously thought. Most HTPs do not
have effective treatments, except for platelet transfusion when bleeding occurs
and in preparation for procedures associated with a risk of bleeding. Preliminary
clinical evidence suggests that thrombopoietin receptor agonists (TPO-RAs) with
an established use in the treatment of certain acquired thrombocytopenias are
well tolerated and provide clinical benefits in patients with some forms of HTP.
These drugs may therefore be considered for the treatment of HTPs in clinical
practice. However, caution and close monitoring are recommended, owing to the
absence of long-term safety data and the potential risks posed by prolonged bone
marrow stimulation in certain HTPs. In this review, we summarize the available
clinical data on TPO-RAs in the treatment of HTPs, and discuss their use in
patients with these disorders. We believe that TPO-RAs will play a major role in
the treatment of HTPs, particularly myosin heavy chain 9-related disease, Wiskott
Aldrich syndrome, X-linked thrombocytopenia, and thrombocytopenia caused by THPO
mutations.
PMID- 29956473
TI - Monitoring minimal residual disease by ddPCR in acute lymphoblastic leukemia
associated with the FGFR1 gene rearrangement.
PMID- 29956474
TI - Role of Bone Morphogenetic Protein 2 Polymorphisms in Bone Mineral Density after
the Start of Treatment with Atorvastatin.
PMID- 29956476
TI - Ultrastable Potassium Storage Performance Realized by Highly Effective Solid
Electrolyte Interphase Layer.
AB - Potassium ion-batteries (PIBs) have attracted tremendous attention recently due
to the abundance of potassium resources and the low standard electrode potential
of potassium. Particularly, the solid-electrolyte interphase (SEI) in the anode
of PIBs plays a vital role in battery security and battery cycling performance
due to the highly reactive potassium. However, the SEI in the anode for PIBs with
traditional electrolytes is mainly composed of organic compositions, which are
highly reactive with air and water, resulting in inferior cycle performance and
safety hazards. Herein, a highly stable and effective inorganic SEI layer in the
anode is formed with optimized electrolyte. As expected, the PIBs exhibit an
ultralong cycle performance over 14 000 cycles at 2000 mA g-1 and an ultrahigh
average coulombic efficiency over 99.9%.
PMID- 29956475
TI - Deoxycholic acid activates epidermal growth factor receptor and promotes
intestinal carcinogenesis by ADAM17-dependent ligand release.
AB - High fat diet is implicated in the elevated deoxycholic acid (DCA) in the
intestine and correlated with increased colon cancer risk. However, the potential
mechanisms of intestinal carcinogenesis by DCA remain unclarified. Here, we
investigated the carcinogenic effects and mechanisms of DCA using the intestinal
tumour cells and Apcmin/+ mice model. We found that DCA could activate epidermal
growth factor receptor (EGFR) and promote the release of EGFR ligand amphiregulin
(AREG), but not HB-EGF or TGF-alpha in intestinal tumour cells. Moreover, ADAM-17
was required in DCA-induced promotion of shedding of AREG and activation of
EGFR/Akt signalling pathway. DCA significantly increased the multiplicity of
intestinal tumours and accelerated adenoma-carcinoma sequence in Apcmin/+ mice.
ADAM-17/EGFR signalling axis was also activated in intestinal tumours of DCA
treated Apcmin/+ mice, whereas no significant change occurred in tumour adjacent
tissues after DCA exposure. Conclusively, DCA activated EGFR and promoted
intestinal carcinogenesis by ADAM17-dependent ligand release.
PMID- 29956477
TI - Banff Lung Report: Current knowledge and future research perspectives for
diagnosis and treatment of pulmonary antibody-mediated rejection (AMR).
AB - The Lung session of the 2017 14th Banff Foundation for Allograft Pathology
Conference, Barcelona focused on the multiple aspects of antibody-mediated
rejection (AMR) in lung transplantation. Multidimensional approaches for AMR
diagnosis, including classification, histological and immunohistochemical
analysis, and donor- specific antibody (DSA) characterization with their current
strengths and limitations were reviewed in view of recent research. The group
also discussed the role of tissue gene expression analysis in the context of
unmet needs in lung transplantation. The current best practice for monitoring of
AMR and the therapeutic approach are summarized and highlighted in this report.
The working group reached consensus of the major gaps in current knowledge and
focused on the unanswered questions regarding pulmonary AMR. An important outcome
of the meeting was agreement on the need for future collaborative research
projects to address these gaps in the field of lung transplantation.
PMID- 29956478
TI - In Vitro Screening of Six Protein Kinase Inhibitors for Time-Dependent Inhibition
of CYP2C8 and CYP3A4: Possible Implications with regard to Drug-Drug
Interactions.
AB - Several protein kinase inhibitors have been reported to affect cytochrome P450
(CYP) 3A by time-dependent inhibition. Herein, we tested a set of six kinase
inhibitors for time-dependent inhibition of CYP2C8 and CYP3A4 in human liver
microsomes. Dovitinib, midostaurin and nintedanib exhibited an increased
inhibition of CYP3A4 after a 30-min. pre-incubation with NADPH, as compared to no
pre-incubation (IC50 shift >1.5). Masitinib, trametinib and vatalanib did not
affect CYP2C8 or CYP3A4 by time-dependent inhibition (IC50 shift <1.5). The
inhibitory mechanism of CYP3A4 by midostaurin and nintedanib, but not by
dovitinib, was consistent with irreversible mechanism-based inhibition. The
maximal inactivation rate (kinact ) and inhibitor concentration that supports
half-maximal rate of inactivation (KI ) values of midostaurin and nintedanib were
0.052 1/min. and 2.72 MUM, and 0.025 1/min. and 17.3 MUM, respectively. According
to static predictions, inactivation of CYP3A4 by nintedanib was unlikely to cause
drug-drug interactions with clinically used doses of nintedanib, whereas
midostaurin was predicted to increase the plasma exposure to CYP3A4-dependent
substrates several fold. Furthermore, based on reversible inhibition, masitinib
and vatalanib were predicted to increase the plasma exposure to sensitive CYP2C8
and CYP3A4 substrates by >=2-fold. In summary, our data identify midostaurin and
nintedanib as time-dependent inhibitors of CYP3A4 and detect a risk of drug-drug
interactions between vatalanib and CYP2C8 substrates, and between masitinib,
midostaurin and vatalanib and CYP3A4 substrates. The liability of kinase
inhibitors to affect CYP enzymes by time-dependent inhibition may have long-term
consequences, in terms of drug-drug interactions and toxicities.
PMID- 29956479
TI - Association between different types of comorbidity and disease burden in patients
with diabetes.
AB - BACKGROUND: This study examined the association between different types of
comorbidities and the quality of diabetes care, health-related quality of life
(HRQoL), and total health care expenditure. METHODS: Adult patients with diabetes
were identified from the 2011 to 2013 Medical Expenditure Panel Survey, a
nationally representative survey of the civilian non-institutionalized US
population. Twenty different chronic conditions were captured and categorized as:
(i) diabetes only; (ii) diabetes plus concordant (diabetes-related) comorbidity
only; and (iii) diabetes plus one or more discordant (non-diabetes-related)
comorbidities. Disease burden outcomes included the process of diabetes care (eye
and foot examinations, HbA1c and cholesterol tests, influenza vaccination),
HRQoL, and total health care expenditure. Multivariable models were used to
examine associations between the type of comorbidity and outcomes. RESULTS: A
sample of 8292 patients with diabetes was identified, of which 11.4% had diabetes
only, 40.5% had concordant comorbidity only, and 48.1% reported one or more
discordant comorbidities. Patients with diabetes and either type of comorbidity
received better quality of diabetes care than those without a comorbidity.
However, patients with discordant comorbidity showed significantly lower HRQoL
measures and higher health care expenditure than those with concordant
comorbidity. Adjusted total mean annual expenditure was US$4891, $6326, and $9210
for those with diabetes only and those with diabetes with one concordant or one
discordant comorbidity, respectively. CONCLUSIONS: Higher disease burden in
patients with diabetes was associated with discordant rather than concordant
comorbidity. Future interventional studies evaluating patient-centered care
models addressing different types of comorbidity are necessary to better manage
these complex patients.
PMID- 29956480
TI - Graphene-coated magnetic-sheet solid-phase extraction followed by high
performance liquid chromatography with fluorescence detection for the
determination of aflatoxins B1 , B2 , G1 , and G2 in soy-based samples.
AB - A new method named graphene-coated magnetic-sheet solid-phase extraction based on
a magnetic three-dimensional graphene sorbent was developed for the extraction of
aflatoxins prior to high-performance liquid chromatography with fluorescence
detection. The use of a perforated magnetic-sheet for fixing the magnetic
nanoparticles is a new feature of the method. Hence, the adsorbent particles can
be separated from sample solution without using an external magnetic field. This
made the procedure very simple and easy to operate so that all steps of the
extraction process (sample loading, washing, and desorption) were carried out
continuously using two lab-made syringe pumps. The factors affecting the
performance of extraction procedure such as the extraction solvent, adsorbent
dose, sample loading flow rate, ionic strength, pH, and desorption parameters
were investigated and optimized. Under the optimal conditions, the obtained
enrichment factors and limits of detection were in the range of 205-236 and 0.09
0.15 MUg/kg, respectively. The relative standard deviations were <3.4 and 7.5%
for the intraday (n = 6) and interday (n = 4) precisions, respectively. The
developed method was successfully applied to determine aflatoxins B1 , B2 , G1 ,
and G2 in different soy-based food samples.
PMID- 29956481
TI - Integration of "Omics" Strategies for Biomarkers Discovery and for the
Elucidation of Molecular Mechanisms Underlying Brugada Syndrome.
AB - PURPOSE: The Brugada syndrome (BrS) is a severe inherited cardiac disorder. Given
the high genetic and phenotypic heterogeneity of this disease, three different
"omics" approaches are integrated in a synergic way to elucidate the molecular
mechanisms underlying the pathophysiology of BrS as well as for identifying
reliable diagnostic/prognostic markers. EXPERIMENTAL DESIGN: The profiling of
plasma Proteome and MiRNome is perfomed in a cohort of Brugada patients that were
preliminary subjected to genomic analysis to assess a peculiar gene mutation
profile. RESULTS: The integrated analysis of "omics" data unveiled a cooperative
activity of mutated genes, deregulated miRNAs and proteins in orchestrating
transcriptional and post-translational events that are critical determining
factors for the development of the Brugada pattern. CONCLUSIONS AND CLINICAL
RELEVANCE: This study provides the basis to shed light on the specific molecular
fingerprints underlying BrS development and to gain further insights on the
pathogenesis of this life-threatening cardiac disease.
PMID- 29956482
TI - Maternal Apolipoprotein B100 Serum Levels are Diminished in Pregnancies with
Intrauterine Growth Restriction and Differentiate from Controls.
AB - PURPOSE: Intrauterine growth restriction, a major cause of fetal morbidity and
mortality, is defined as a condition in which the fetus does not reach its
genetically given growth potential. Screening for intrauterine growth restriction
biomarkers in the mother's blood would be of great help for optimal pregnancy
management and timing of delivery as well as for identifying fetuses requiring
further surveillance during their infancies. EXPERIMENTAL DESIGN: A multiplexing
serological assay based on liquid chromatography-multiple-reaction-monitoring
mass spectrometry is applied for distinguishing serum samples of pregnant women.
RESULTS: Assessment of concentrations of apolipoproteins and of proteins that
belong to the lipid transport system is performed with maternal serum samples,
consuming only 10 MUL of serum per multiplex assay from each patient. Of all
investigated proteins the serum concentrations of apolipoprotein B100 shows the
greatest power for discriminating intrauterine growth restriction from control
samples, reaching areas under curves above 0.85 in receiver-operator
characteristics analyses. CONCLUSIONS: These results indicate the potential of
liquid chromatography-multiple-reaction-monitoring mass spectrometry to become of
clinical importance in the future for intrauterine growth restriction risk
assessment based on maternal apolipoprotein B100 serum levels.
PMID- 29956483
TI - Synthesis of Hierarchical 4H/fcc Ru Nanotubes for Highly Efficient Hydrogen
Evolution in Alkaline Media.
AB - Hierarchical metal nanostructures containing 1D nanobuilding blocks have
stimulated great interest due to their abundant active sites for catalysis.
Herein, hierarchical 4H/face-centered cubic (fcc) Ru nanotubes (NTs) are
synthesized by a hard template-mediated method, in which 4H/fcc Au nanowires
(NWs) serve as sacrificial templates which are then etched by copper ions (Cu2+ )
in dimethylformamide. The obtained hierarchical 4H/fcc Ru NTs contain ultrathin
Ru shells (5-9 atomic layers) and tiny Ru nanorods with length of 4.2 +/- 1.1 nm
and diameter of 2.2 +/- 0.5 nm vertically decorated on the surface of Ru shells.
As an electrocatalyst for the hydrogen evolution reaction in alkaline media, the
hierarchical 4H/fcc Ru NTs exhibit excellent electrocatalytic performance, which
is better than 4H/fcc Au-Ru NWs, commercial Pt/C, Ru/C, and most of the reported
electrocatalysts.
PMID- 29956484
TI - Comment on internal cyclopexy for complicated traumatic cyclodialysis cleft.
PMID- 29956485
TI - Sevoflurane Impairs Insulin Secretion and Tissue-Specific Glucose Uptake In Vivo.
AB - The use of anaesthetics severely influences substrate metabolism. This poses
challenges for patients in clinical settings and for the use of animals in
diabetes research. Sevoflurane can affect regulation of glucose homoeostasis at
several steps, but the tissue-specific response remains to be determined. The aim
of the study was to investigate the pharmacological effect of sevoflurane
anaesthesia on glucose homoeostasis during hyperinsulinaemic clamp conditions,
the gold standard method for assessment of whole-body insulin sensitivity.
Conscious mice (n = 6) and mice under sevoflurane anaesthesia (n = 8) underwent a
hyperinsulinaemic clamp where constant infusion of insulin and donor blood was
administered during variable glucose infusion to maintain isoglycaemia. 2-[1-14
C]-deoxy-D-glucose was infused to determine tissue-specific uptake of glucose in
adipose tissue, heart, brain and skeletal muscle. Sevoflurane anaesthesia
severely impaired insulin-stimulated whole-body glucose uptake demonstrated by a
50% lower glucose infusion rate (GIR). This was associated with decreased glucose
uptake in brain, soleus, triceps and gastrocnemius muscles in sevoflurane
anaesthetized mice compared to conscious mice. Plasma-free fatty acids (FFA), a
potent inducer of insulin resistance, increased by 42% in mice during sevoflurane
anaesthesia. In addition, insulin secretion from pancreatic beta-cell was lower
in fasted, anaesthetized mice. Sevoflurane anaesthesia impairs insulin secretion,
induces insulin resistance in mice and reduces glucose uptake in non-insulin
sensitive tissue like the brain. The underlying mechanisms may involve
sevoflurane-induced mobilization of FFA.
PMID- 29956486
TI - Prioritising references for systematic reviews with RobotAnalyst: A user study.
AB - Screening references is a time-consuming step necessary for systematic reviews
and guideline development. Previous studies have shown that human effort can be
reduced by using machine learning software to prioritise large reference
collections such that most of the relevant references are identified before
screening is completed. We describe and evaluate RobotAnalyst, a Web-based
software system that combines text-mining and machine learning algorithms for
organising references by their content and actively prioritising them based on a
relevancy classification model trained and updated throughout the process. We
report an evaluation over 22 reference collections (most are related to public
health topics) screened using RobotAnalyst with a total of 43 610 abstract-level
decisions. The number of references that needed to be screened to identify 95% of
the abstract-level inclusions for the evidence review was reduced on 19 of the 22
collections. Significant gains over random sampling were achieved for all reviews
conducted with active prioritisation, as compared with only two of five when
prioritisation was not used. RobotAnalyst's descriptive clustering and topic
modelling functionalities were also evaluated by public health analysts.
Descriptive clustering provided more coherent organisation than topic modelling,
and the content of the clusters was apparent to the users across a varying number
of clusters. This is the first large-scale study using technology-assisted
screening to perform new reviews, and the positive results provide empirical
evidence that RobotAnalyst can accelerate the identification of relevant studies.
The results also highlight the issue of user complacency and the need for a
stopping criterion to realise the work savings.
PMID- 29956487
TI - A Biotinylated and Endoplasmic Reticulum-Targeted Glutathione-Responsive Zinc(II)
Phthalocyanine for Targeted Photodynamic Therapy.
AB - A biotinylated glutathione (GSH)-responsive zinc(II) phthalocyanine has been
prepared and characterized. With a 2,4-dinitrobenzenesulfonyl moiety, its
fluorescence emission and singlet oxygen generation were silenced in its intact
state. Upon exposure to high concentration of GSH, its photosensitizing
properties were restored in phosphate buffered saline and inside tumor cells. It
also showed preferential uptake on HepG2 human hepatocarcinoma cells (with higher
biotin receptor expression) rather than Chinese hamster ovary (CHO) cells (with
lower biotin receptor expression). Upon irradiation, it caused photocytotoxicity
with an IC50 value down to 0.1 MUm on HepG2 cells. Moreover, it can localize in
the endoplasmic reticulum (ER), causing ER stress after light irradiation.
PMID- 29956488
TI - Zinc-Coordinated Nitrogen-Codoped Graphene as an Efficient Catalyst for Selective
Electrochemical Reduction of CO2 to CO.
AB - Electrochemical reduction of CO2 to value-added chemicals by using renewable
electricity offers a promising strategy to deal with rising CO2 emission and the
energy crisis. Single-site zinc-coordinated nitrogen-codoped graphene (Zn-N-G)
catalyzes the electrochemical reduction of CO2 to CO. The Zn-N-G catalyst
exhibits excellent intrinsic activity toward CO2 reduction, reaching a faradaic
efficiency of 91 % for CO production at a low overpotential of 0.39 V. X-ray
absorption fine structure and X-ray photoelectron spectroscopy both confirm the
presence of isolated Zn-Nx moieties, which act as the key active sites for CO
formation. DFT calculations reveal the origin of enhanced activity for CO2
reduction on Zn-N-G catalysts. This work provide further understanding of the
active centers on transition metal-nitrogen-carbon (M-N-C) catalysts for
electrochemical reduction of CO2 to CO.
PMID- 29956489
TI - Underdocumentation of Obesity by Medical Residents Highlights Challenges to
Effective Obesity Care.
AB - OBJECTIVE: The goal of this study was to determine attitudes and practices of
physicians in training with respect to the evaluation and treatment of obesity.
METHODS: Resident-generated admission and discharge notes of all 1,765 general
medicine hospital admissions during 4 nonconsecutive months were analyzed, and
any references to weight, obesity, BMI, adiposity, and body fat were identified.
The full general resident cohort was then surveyed for perceptions and behaviors
related to obesity. RESULTS: Obesity was considered a highly important medical
issue by 98.5% of residents; 90% correctly identified a class II obesity Stunkard
phenotype, and 80% accurately calculated a BMI given height and weight in metric
units. Residents overestimated inpatient obesity prevalence (estimate = 75%;
actual = 35%) and the rate of obesity recording in the hospital admission note
(estimate = 94%; actual = 49.5%). A BMI or current weight in the admission note
or discharge summary was reported in none of the 1,765 patient records, and only
6% of the patients with obesity had obesity noted in either the inpatient
admission or discharge assessment or plan. CONCLUSIONS: Though residents
recognize obesity and its clinical implications, it is underreported in the
assessment of inpatients. This low level of documenting obesity and its impact on
clinical care planning underscores a missed opportunity to establish appropriate
referrals and initiate treatment at a clinically opportune time.
PMID- 29956490
TI - Systematic investigations of novel validity parameters in urine drug testing and
prevalence of urine adulteration in a two-year cohort.
AB - Urinalysis is well established for drug screening. Various methods of urine
adulteration such as dilution, addition of oxidative/reductive chemicals or
detergents, and handing over urine-like fluids are used to circumvent a positive
screen. Validity parameters such as determination of pH, gravidity, urine
temperature, or testing for oxidative/reductive chemicals are therefore used to
uncover adulterated urine specimens. However, synthetic urine ("fake urine") has
nowadays been used for manipulations, leading to inconspicuous results with
common validity test systems. Therefore, the aims of the study were (a) to
evaluate additional validity parameters, (b) to evaluate the prevalence of urine
adulteration, (c) to identify adulteration markers in purchased fake urine
samples. Urine samples (n = 550) submitted for drug abstinence testing were
analyzed by a standard urine liquid chromatography-tandem mass spectrometry (LC
MS/MS) screening approach using library-assisted identification of 10 different
endogenous biomolecules. The detection rates of biomolecules in authentic samples
were phenylalanine (93.4%), tryptophan (97.1%), propionyl-carnitine (67.1%),
butyryl-carnitine (99.6%), isovaleryl-carnitine (92.8%), hexanoyl-carnitine
(91.0%), heptanoyl-carnitine (97.1%), octanoyl-carnitine (98.9%), and
indoleacetylglutamine (98,2%). Phenylacetylglutamine was detected in each
authentic sample. Based on the detection rates and measured creatinine levels,
six manipulated samples were identified in this study. In two cases, fake urine
was handed over, one time fake urine was most likely used for dilution. Once
dilution with other fluids was used as adulteration method, while in another
sample a detergent solution was handed over. Additionaly, one sample contained
reactive chemicals. All fake urine samples were additionally identified by the
detection of unique polyglycole patterns, which were observed in purchased fake
urine samples.
PMID- 29956491
TI - Addressing the unique needs of adolescent mothers in the fight against HIV.
PMID- 29956492
TI - Biofabrication of a novel leukocyte-fibrin-platelet membrane as a cells and
growth factors delivery platform for tissue engineering applications.
AB - Autologous platelet-rich hemocomponents have emerged as potential biologic tools
for regenerative purpose, but their therapeutic efficacy still remains
controversial. This work represents the characterization study of an innovative
autologous leukocyte-fibrin-platelet membrane (LFPm), which we prepared according
to a novel protocol involving multiple cycles of apheresis. The high content in
fibrinogen gave to our hemocomponent the appearance of a manipulable and
suturable membrane with high elasticity and deformation capacity. Moreover, being
highly enriched with platelets, leukocytes, and monocytes/macrophages, the LFPm
sustained the local release of bioactive molecules (platelet derived growth
factor, vascular endothelial growth factor, interleukin-10, and tumour necrosis
factor alpha). In parallel, the evaluation of stemness potential highlighted also
that the LFPm contained cells expressing pluripotency and multipotency markers
both at the messenger ribonucleic acid (NANOG, SOX2, THY1, NT5E, and ENG) and
surface-protein level (CD44high /CD73+ /CD34+ /CD117+ /CD31+ ). Finally,
biodegradation analysis interestingly showed a good stability of the membrane for
at least 3 weeks in vitro and 1 week in vivo. In both cases, biodegradation was
associated with progressive exposure of fibrin scaffold, loss/migration of
cellular elements, and release of growth factors. Overall, collected evidence
could shed some light on the regenerative effect that LFPms may exert after the
autologous implant on a defect site.
PMID- 29956494
TI - Inward Glucose Transfer Accounts for Insulin-Dependent Increase in Brain Glucose
Metabolism Associated with Diet-Induced Obesity.
AB - OBJECTIVE: There is a general agreement that there are changes in brain
metabolism in insulin-resistant individuals during conditions of
hyperinsulinemia. However, the impact on obesity is unclear, and the metabolic
constants underlying these modifications are unknown. The aim of this study was
to evaluate these changes in a large animal model of diet-induced obesity.
METHODS: Twenty adult miniature pigs were fed with either an obesogenic diet or a
regular diet for 5 months. At that time, fat deposition was evaluated using
computed tomography scanning, and 18 fluorodeoxyglucose positron emission
tomography images were acquired dynamically both in the fasted state and during a
euglycemic-hyperinsulinemic clamp. Glucose uptake rates and pixel-wise modeled
brain volumes were calculated together with brain connectivity. RESULTS: Whole
body insulin sensitivity was reduced by more than 50% in the obesity group.
During insulin stimulation, whole-brain insulin-induced increased glucose uptake
was unaltered in lean animals but increased markedly in the animals with obesity.
The increased glucose uptake reflected an increase in the inward transfer without
changes in phosphorylation or outward brain transport. Connectivity was increased
in the animals with obesity CONCLUSIONS: Diet-induced obesity is associated with
an increase in insulin-stimulated brain glucose uptake as a consequence of a
larger inward transfer. These changes occurred together with an increased
connectivity in reference to regions associated with memory recollection.
PMID- 29956493
TI - Outcome of 449 adult patients with rhabdomyosarcoma: an observational
ambispective nationwide study.
AB - Five-year overall survival (OS) of localized RMS exceeds 70% in children (<18)
but is very poor in adult patients. We analyzed the outcome and prognostic
factors (PF) of a national series of adult patients with RMS in a large study.
The study population consisted of two different cohorts: a retrospective cohort
(157 adult patients treated in 13 reference centers between 05/1981 and 02/2010)
and the prospective cohort (292 patients with RMS diagnosed and treated between
01/2010 and 12/2014 in France) included in the NetSarc database. A descriptive
analysis of patients' characteristics and prognostic factors was conducted on
both series which were compared. In the retrospective series, histological
subtypes were embryonal (E-RMS) for 21% of patients, alveolar (A-RMS) for 35% of
patients, and "adult-type" P-RMS (pleomorphic, spindle cell RMS, not otherwise
specified) (P) for 44% patients. This distribution significantly differed in the
prospective cohort: A-RMS: 18%; E-RMS: 17%; and P-RMS 65%. With a median follow
up of 8.5 years, 5-year OS for localized RMS and advanced RMS (with nodes and/or
metastases) was 43% and 5%, respectively, (P < 0.0001), and median OS was 51, 33,
and 16 months for E-RMS, A-RMS, and P-RMS, respectively, in the retrospective
cohort. The median OS was less than 40 months for the prospective nationwide
cohort for the entire population. In a multivariate analysis of the retrospective
study, independent prognostic factors for OS were A-RMS, R0 resection, and
adjuvant radiotherapy (RT). For localized RMS, age and use of pediatric
chemotherapy (CT) regimen are independent prognostic factors. Adult patients with
RMS have a poorer overall survival than pediatric patients, and survival varies
considerably across histological subtypes.
PMID- 29956495
TI - Weight and Shape Concern Impacts Weight Gain Prevention in the SNAP Trial:
Implications for Tailoring Intervention Delivery.
AB - OBJECTIVE: The Study of Novel Approaches to Weight Gain Prevention (SNAP) trial
demonstrated that two self-regulatory interventions prevented weight gain in
young adults. Weight and shape concern (WSC) at baseline was evaluated as a
moderator of weight outcomes at 24 months. METHODS: Young adults (n = 599) were
randomized to self-regulation with small changes (to create 200 kcal/day
deficit), self-regulation with large changes (to facilitate preemptive weight
loss of 5-10 lb), or self-guided control. WSC was assessed by using one item from
the Eating Disorders Assessment. ANOVA was used to examine whether the
association between baseline level of WSC and percent weight change over 24
months differed across treatment conditions. RESULTS: Approximately 22% of
participants reported high WSC (37% moderate; 41% low). WSC and treatment
condition interacted to influence weight change at 24 months (P = 0.03).
Individuals with high WSC gained weight in the large changes group (WSC least
squares means +/- SE, high: + 0.73% +/- 1.19%; moderate: -2.74% +/- 0.84%; low:
2.41% +/- 0.79%). The small changes condition was particularly effective for
those with high WSC (high WSC: -2.49% +/- 1.16%; moderate: -0.60% +/- 0.88%; low:
-0.71% +/- 0.80%). WSC did not impact weight change among control participants.
CONCLUSIONS: Individuals with high WSC may benefit from a small-changes approach
to weight gain prevention. These findings indicate WSC may be used to match
individuals to weight gain prevention treatment conditions.
PMID- 29956496
TI - In memoriam: Professor David Cooper (1949 to 2018).
PMID- 29956498
TI - Case of chronic pain after laparoscopic percutaneous extraperitoneal closure in
an adolescent girl with inguinal hernia in which open repair was effective.
AB - Chronic pain after laparoscopic percutaneous extraperitoneal closure is very
rare. Here, we report a case of chronic pain after laparoscopic percutaneous
extraperitoneal closure in an adolescent patient with inguinal hernia who
underwent open repair. A 15-year-old girl was diagnosed with a left indirect
inguinal hernia, and laparoscopic percutaneous extraperitoneal closure was
performed. However, 6 months later, after strenuous exercise, she developed
localized pain around the hernia site. Her pain was well controlled by internal
treatment but failed to completely resolve. The pain type was somatic, Tinel's
sign was negative, and there was no recurrence of the inguinal hernia. Because
she strongly wished to undergo surgery, the Potts procedure with removal of the
ligature and excision of the round ligament was performed. Her pain improved
after surgery, and further medical treatment was not required. The Potts
procedure may be an effective treatment for chronic pain such as in this case.
PMID- 29956497
TI - Weight Perception, Weight Stigma Concerns, and Overeating.
AB - OBJECTIVE: Perceiving one's own weight status as being overweight is a likely
motivation for weight loss. However, self-perceived overweight status has also
been found to be associated with overeating and weight gain. This study examined
whether weight stigma concerns explain why individuals who perceive their weight
status as overweight are at increased risk of overeating. METHODS: We conducted
two survey studies of United States adults (N = 1,236) in which we assessed
whether weight stigma concerns explain the cross-sectional relationship between
perceived overweight and overeating tendencies. RESULTS: Across two studies, the
cross-sectional relationship between perceived overweight and overeating
tendencies was in part explained by weight stigma concerns. Participants who
perceived their weight as "overweight" reported greater weight stigma concerns
than participants who perceived their weight as "about right," and this explained
23.3% (Study 1) to 58.6% (Study 2) of the variance in the relationship between
perceived overweight and overeating tendencies. CONCLUSIONS: Weight stigma
concerns may explain why perceiving one's own weight status as overweight is
associated with an increased tendency to overeat.
PMID- 29956499
TI - Long-term results of transurethral endoscopic excision using the holmium laser
for urethral perforation of synthetic slings.
AB - OBJECTIVE: This study reports on the long-term results of transurethral
endoscopic excision using the Holmium laser (TEEH) for large urethral perforation
(UP; defined as involving one-quarter or more of the urethral circumference) from
synthetic slings. METHODS: Charts of women treated with TEEH for large UP were
reviewed. TEEH was performed using a 365-MUm laser fiber passed inside an open
ended ureteral catheter positioned in a holmium laser enucleation of the prostate
(HoLEP) sheath to stabilize the laser fiber. Data extracted included patient
demographics, clinical presentations, surgical details, postoperative functional
outcomes and complications, and any secondary repairs. RESULTS: From 2011 to
2016, 12 women underwent TEEH. The mean interval between sling placement and
first TEEH was 47 months (range 10-161 months). The types of slings included
transvaginal tape (n = 2), transobturator tape (n = 4), mini-invasive (n = 4),
and Solyx (1), or were not specified (n = 1). The mean number of TEEH procedures
was 1.6 (range 1-3), and the mean length of initial treatment was 40 min (range
15-79 min), with subsequent treatments <30 min. Mean follow-up time was 43 months
(range 14-70). Resolution of UP by TEEH alone was achieved in 6 patients, with 2
requiring multiple TEEH. Six patients underwent secondary vaginal mesh sling
excision alone or with an associated repair including 2 small distal
urethrovaginal fistulas. CONCLUSION: TEEH is a minimally invasive procedure that
can avoid a more complex initial urethral reconstruction and should be considered
for treating large UP. Secondary repairs for residual small UP or associated
lower urinary tract symptomatology may be necessary and patients should be
counseled accordingly.
PMID- 29956501
TI - CD4+ and CD8+ T-Cell-Specific DNA Cytosine Methylation Differences Associated
With Obesity.
AB - OBJECTIVE: Lifestyle factors associated with obesity may alter epigenome
regulated gene expression. Most studies examining epigenetic changes in obesity
have analyzed DNA 5'-methylcytosine (5mC) in whole blood, representing a weighted
average of several distantly related and regulated leukocyte classes. To examine
leukocyte-specific differences associated with obesity, a pilot study examining
5mC in three distinct leukocyte types isolated from peripheral blood of women
with normal weight and obesity was conducted. METHODS: CD4+ T cells, CD8+ T
cells, and CD16+ neutrophils were reiteratively isolated from blood, and 5mC
levels were measured across >450,000 CG sites. RESULTS: Nineteen CG sites were
differentially methylated between women with obesity and with normal weight in
CD4+ cells, 16 CG sites in CD8+ cells, and 0 CG sites in CD16+ neutrophils (q <
0.05). There were no common differentially methylated sites between the T-cell
types. The amount of visceral adipose tissue was strongly associated with the
methylation level of 79 CG sites in CD4+ cells, including 4 CG sites in CLSTN1's
promoter, which, this study shows, may regulate its expression. CONCLUSIONS: The
methylomes of various leukocytes respond differently to obesity and levels of
visceral adipose tissue. Highly significant differentially methylated sites in
CD4+ and CD8+ cells in women with obesity that have apparent biological relevance
to obesity were identified.
PMID- 29956503
TI - The Effects of If-Then Plans on Weight Loss: Results of the McGill CHIP Healthy
Weight Program Randomized Controlled Trial.
AB - OBJECTIVE: The NIH-developed Diabetes Prevention Program (DPP) is successful in
achieving clinically significant weight loss in individuals with
overweight/obesity when delivered one-on-one. The group-based DPP is less
effective, with average weight losses of only 3.5%. The objective of this study
was to increase weight loss outcomes of the group-based DPP by integrating habit
formation tools (i.e., if-then plans). This two-arm randomized controlled trial
tested the efficacy of the habit formation-enhanced group-based DPP compared with
the standard group-based DPP on changes in body weight (primary outcome). This
study presents the 3- and 12-month results of this 24-month trial. METHODS: A
total of 208 participants were randomly assigned to the standard or enhanced DPP,
and 172 participated. Participants were men and women with overweight/obesity who
self-reported less than 200 min/wk of exercise. RESULTS: Both groups achieved
high weight losses at 3 (5.76%) and 12 (9.98%) months, with no differences
between groups (chi2 < 1). Both groups improved in blood pressure and physical
activity. CONCLUSIONS: If-then plans did not result in higher weight loss. Both
program versions resulted in higher weight loss than the group-based DPP. This
may suggest that cognitive behavioral therapy skills of the coaches (clinical
psychology doctoral students) was a key factor in treatment outcome.
PMID- 29956502
TI - Stanniocalcin 2 expression is associated with a favourable outcome in male breast
cancer.
AB - Breast cancer can occur in either gender; however, it is rare in men, accounting
for <1% of diagnosed cases. In a previous transcriptomic screen of male breast
cancer (MBC) and female breast cancer (FBC) occurrences, we observed that
Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was
to confirm the expression of STC2 in MBC and to investigate whether this had an
impact on patient prognosis. Following an earlier transcriptomic screen, STC2
gene expression was confirmed by RT-qPCR in matched MBC and FBC samples as well
as in tumour-associated fibroblasts derived from each gender. Subsequently, STC2
protein expression was examined immunohistochemically in tissue microarrays
containing 477 MBC cases. Cumulative survival probabilities were calculated using
the Kaplan-Meier method and multivariate survival analysis was performed using
the Cox hazard model. Gender-specific STC2 gene expression showed a 5.6-fold
upregulation of STC2 transcripts in MBC, also supported by data deposited in
OncomineTM. STC2 protein expression was a positive prognostic factor for disease
free survival (DFS; Log-rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017,
HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall
survival (Log-rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59;
stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for
patient age at diagnosis, node staging, tumour size, ER, and PR status revealed
that total STC2 expression as well as expression in tumour cells was an
independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p =
0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in
MBC where it is an independent prognostic factor for DFS.
PMID- 29956504
TI - The Improved Delivery to Breast Cancer Based on a Novel Nanocarrier Modified with
High-Affinity Peptides Discovered by Phage Display.
AB - Ligand-targeted nanosystems have the potential to realize site-specific tumor
therapy and alleviate unwanted side effects of many chemotherapeutic agents, and
one of the most key issues seems to be the construction of an effective
nanocarrier. Based on different processes of phage display techniques, 38 cell
binding peptides and 32 cell-internalizing peptides are discovered. Four of these
ligand peptides [FIPFDPMSMRWE (FIP), NASSFPTNSRWA (NAS), GLHTSATNLYLH (GLH), and
ALAVAPSRWWNE (ALA), respectively] exhibit high affinity to MCF7 human breast
cancer cells. Among them, NAS and ALA are reported for the first time, whose
affinities are 20.6 and 76.3 times that of the random peptide control,
respectively. Both NAS and ALA modifications to doxorubicin-loaded lipid
nanosytems [LP(DOX)] show stronger tumor inhibition, longer animal survival time,
and less body weight loss, compared to unmodified or control peptide modified
nanosystems, on an MCF7 tumor-bearing mouse model. In conclusion, the cell
binding peptide NAS and cell-internalizing peptide ALA can be used for ligand
targeted delivery of antitumor drugs. It seems that the in vivo antitumor effect
of these ligand-targeted nanosystems is closely related to their ligand-cell
affinity, but fairly tolerant of the ligand types.
PMID- 29956500
TI - A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by
inducing low immune response.
AB - The major histocompatibility complex (MHC) is most closely associated with
nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has
proven challenging for the discovery of causal MHC loci or genes. We conducted a
targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage
replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent.
Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status
in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter
assay and chromatin immunoprecipitation (ChIP) were used to assess the
transcription factor binding site. We discovered that a novel SNP rs117565607_A
at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 * 10
19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue
samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found
the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was
lower than TT. According to computational prediction, rs117565607 locus was a
binding site for the transcription factor Yin Yang 1 (YY1). We observed that the
luciferase activity of YY1 which is binding to the A allele of rs117565607 was
suppressed. ChIP data showed that YY1 was binding with T not A allele.
Significance analysis of microarray suggested that TRIM26 downregulation was
related to low immune response in NPC. We have identified a novel gene TRIM26 and
a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional
process and established a new functional link between TRIM26 downregulation and
low immune response in NPC.
PMID- 29956505
TI - Introduction to the special issue-Developmental plasticity in reptiles:
Physiological mechanisms and ecological consequences.
AB - Scientific interest in developmental plasticity spans many disciplines, and
research on reptiles has provided many insights into this field. We highlight
these contributions, review the field's history, and introduce the special issue
on this topic .
PMID- 29956506
TI - In-vivo Raman spectroscopy: from basics to applications.
AB - For more than two decades, Raman spectroscopy has found widespread use in
biological and medical applications. The instrumentation and the statistical
evaluation procedures have matured, enabling the lengthy transition from ex-vivo
demonstration to in-vivo examinations. This transition goes hand-in-hand with
many technological developments and tightly bound requirements for a successful
implementation in a clinical environment, which are often difficult to assess for
novice scientists in the field. This review outlines the required instrumentation
and instrumentation parameters, designs, and developments of fiber optic probes
for the in-vivo applications in a clinical setting. It aims at providing an
overview of contemporary technology and clinical trials and attempts to identify
future developments necessary to bring the emerging technology to the clinical
end users. A comprehensive overview of in-vivo applications of fiber optic Raman
probes to characterize different tissue and disease types is also given.
PMID- 29956507
TI - Photodynamic therapy with chlorin-based photosensitizer at 405 nm: numerical,
morphological, and clinical study.
AB - Employment of chlorin-based photosensitizers (PSs) provides additional advantages
to photodynamic therapy (PDT) due to absorption peak around 405 nm allowing for
superficial impact and efficient antimicrobial therapy. We report on the
morphological and clinical study of the efficiency of PDT at 405 nm employing
chlorin-based PS. Numerical studies demonstrated difference in the distribution
of absorbed dose at 405 nm in comparison with traditionally employed wavelength
of 660 nm and difference in the in-depth absorbed dose distribution for skin and
mucous tissues. Morphological study was performed at the inner surface of rabbit
ear with histological examinations at different periods after PDT procedure.
Animal study revealed tissue reaction to PDT consisting in edema manifested most
in 3 days after the procedure and neoangiogenesis. OCT diagnostics was confirmed
by histological examination. Clinical study included antimicrobial PDT of pharynx
chronic inflammatory diseases. It revealed no side effects or complications of
the PDT procedure. Pharyngoscopy indicated reduction of inflammatory
manifestations, and, in particular cases, hypervascularization was observed.
Morphological changes were also detected in the course of monitoring, which are
in agreement with pharyngoscopy results. Microbiologic study after PDT revealed
no pathogenic bacteria; however, in particular cases, saprophytic flora was
detected.
PMID- 29956509
TI - [In process].
PMID- 29956508
TI - Automatic measurement of global retinal circulation in fluorescein angiography.
AB - Examination of the retinal circulation in patients with retinal diseases is a
clinical routine for ophthalmologists. In the present work, an automatic method
is proposed for measuring the global retinal circulation in fluorescein
angiography (FA). First, the perfusion region in FA images is segmented using a
multiscale line detector. Then, the time evolution of the perfusion area is
modeled using damped least-squares regression. Based on the perfusion area
profile, some circulation parameters are defined to describe quantitatively the
global retinal circulation. The effectiveness of the proposed method is tested
using our own and public datasets, with reasonable results and satisfactory
accuracy compared with manual measurement. The proposed method has good computing
efficiency and thus has potential to be used in clinical practice for evaluation
of global retinal circulation.
PMID- 29956510
TI - Bipolar disorder: clinical overview.
AB - Bipolar disorder is a severe psychiatric disorder, characterized by depressive,
manic and mixed episodes. The illness affects about 1-2 % of the population.
Bipolar I disorders affect both genders equally, whereas bipolar II disorders
seem to occur more frequently in women. The classification of the different
subtypes of bipolar disorders is done depending on the severity and frequency of
the episodes. Other subtypes beside bipolar I and bipolar II disorder are rapid
cycling (more than 4 episodes of mania, depression, hypomania or mixed state in
one year) and cyclothymia (hypomanic and subdepressive symptoms over a two year
period). Besides a thorough psychiatric and neurological examination, further
clinical tests should be performed in order to exclude differential diagnosis
(psychiatric as well as neurological and somatic diseases). The course of the
illness is often negatively affected by the high frequency of psychiatric and
somatic comorbidities. After all the prognosis of bipolar disorder is depending
on the individual course of the illness. Notably comorbidities and psychotic
symptoms seem to have a negative influence on the prognosis.
PMID- 29956511
TI - Basic data for bipolar disorders: genetics, neurobiology and pharmacology.
AB - Bipolar disorders are quite common (lifetime prevalence 1-2 %) and have a
substantial genetic risk (total heritability about 80 %). However, the
contribution of individual genes to the total genetic risk is very small.
Accordingly, no specific genes are known which show a larger contribution.
Nevertheless, many of the known genes involved encode for proteins important for
neural plasticity, mitochondrial function, dopaminergic neurotransmission and
calcium channels. Similarly, the few data about neurobiological alterations in
the brains of bipolar patients also point into the same direction. However, these
observations are not very specific. A possible exception might be mitochondrial
dysfunction seen in bipolar patients, which could integrate several of the other
findings into one concept. The pharmacology of the drugs used to treat bipolar
disorders is also not pointing to one common mechanism of action. While the
mechanisms of action of antidepressants and antipsychotics probably are not
different from the mechanisms relevant to treat depression and schizophrenia, the
mechanisms of the anticonvulsants used in bipolar disorders (valproic acid,
carbamazepine, lamotrigine) are probably different from their mechanism of action
as anticonvulsant drugs. More likely, these drugs improve neuronal plasticity
similarly to lithium and antidepressants.
PMID- 29956512
TI - [In process].
PMID- 29956513
TI - A patient with acute mania after discontinuation of lithium.
AB - The abrupt discontinuation of lithium in patients with bipolar disease puts the
patient at a high risk for a relapse. Lithium is a drug with a narrow therapeutic
index. Intoxications might occur during the treatment. The individual risk
benefit-ratio should be discussed with the patient before starting lithium.
Atypical antipsychotics are an alternative to lithium in the treatment of bipolar
disease. Several guidelines recommend the use of atypical antipsychotics in a
long acting (depot) formulation in bipolar patients (off label use). The long
acting (depot) formulations offer the benefit that during a hypomanic or a
beginning manic episode, the drug can not easily be discontinued. During the
phase of early signs of a beginning manic episode the patients tend not to see
the need to take any medication (lack of insight into illness) which leads to non
adherence that puts the patient at a high risk for a manic episode. If lithium is
prescribed, special counselling is needed, especially about fluid intake and
potential drug interactions (NSAIDS, ACE-inhibitors, diuretics).
PMID- 29956514
TI - [In process].
PMID- 29956515
TI - [In process].
PMID- 29956516
TI - [In process].
PMID- 29956517
TI - [In process].
PMID- 29956518
TI - [In process].
PMID- 29956519
TI - [In process].
PMID- 29956520
TI - [In process].
PMID- 29956521
TI - [In proces].
PMID- 29956522
TI - Outpatient palliative care - a multiprofessional challenge.
AB - Life-threatening illness and the dying of a person presents a complex and
particularly burdensome challenge for the person affected as well as for their
relatives. This also applies to the professionals involved in caring and
supporting the terminally ill patient. For this reason, palliative care has
become a pioneer of a networked multi-professional and multi-perspective thinking
and acting. In hardly any other medical field so many different professional
groups and specialized disciplines work together in such an intensive manner. The
rapid supply of drugs is an essential part of the specialized outpatient
palliative care concept (SAPV). This cooperation is exemplified in this article.
PMID- 29956523
TI - Care of terminally ill patients and palliative sedation.
AB - Caring of very sick and dying people at home during their last phase in life
presents a maximum challenge for patients, their family, relatives and the
palliative care team. Dying stages occur differently in each patient and the
palliative care team must react accordingly. Despite all monitoring and
sufficient treatment for the patient, symptoms can create a highly stressful
situation. After careful consideration in these cases, a palliative sedation can
be considered. Guidelines of German and European societies describe indications,
as well as the implementation. A highly complex casuistics demonstrates
possibilities and limits of palliative sedation
PMID- 29956525
TI - [In process].
PMID- 29956524
TI - Pharmacists as part of an outpatient palliative care team.
AB - Pharmacists are an integral factor in palliative medical care, especially in the
context of specialised outpatient palliative care (in Germany "SAPV"). As part of
a multi professional team, pharmacists take care of patients especially in
complex supply situations. The drug therapy is always checked for side-effects
and interactions, and the medication is adjusted to application methods which are
still possible (e. g. subcutaneous administration or administration via gastro
intestinal probes). A 24/7 supply of urgently needed medicines needs to be
ensured and clinical nutrition must be suited to the real needs of the patient.
Prompt aseptic manufacturing of analgesic pumps and the supply of medical devices
is a priority of regional specialised pharmacies, whilst the basic support can be
provided by all pharmacies who wish to engage in this ethically demanding field.
PMID- 29956526
TI - Diabetes Stewardship - Pharmaceutical care of adolescents with type 1 diabetes
mellitus provided by community pharmacists.
AB - Diabetes mellitus Type 1 is one of the most common diseases in childhood. Severe,
secondary diseases like hypertension or blindness are results of micro- and
macrovascular complications caused by insufficient glycaemic control. Especially
adolescent patients with type 1 diabetes have a lower adherence rate. The DIADEMA
trial proved that community pharmacist in collaboration with diabetologists and
diabetes advisors can have a positive impact on the therapy of adolescents with
type 1 diabetes. This article highlights and explains which components of the
pharmacist intervention caused the preferable adjustments and improved the
insulin therapy of the patients.
PMID- 29956527
TI - Pharmaceutical care of an adolescent with type 1 diabetes.
AB - This article describes the pharmaceutical care of an adolescent with type 1
diabetes mellitus, who took part in the DIADEMA study. Diabetes was diagnosed for
three years and his baseline HbA1c-value was 9.3 %. In the DIADEMA study
adolescents received pharmaceutical care provided by community pharmacists in
addition to usual care provided by diabetologists and diabetes educators.
Patients in the intervention group received monthly scheduled visits with the
community pharmacists and on-demand telephone calls. Fundamental contents of the
pharmacist?s interventions were in particular self-monitoring of blood glucose,
prevention of acute and long-term diabetes complications and conscientious
consumption of alcohol. Furthermore difficulties in individual insulin therapy
and current life conditions were addressed.
PMID- 29956528
TI - [In process].
PMID- 29956529
TI - [In process].
PMID- 29956530
TI - [In process].
PMID- 29956533
TI - [In process].
PMID- 29956532
TI - [In process]
PMID- 29956531
TI - [In process].
PMID- 29956534
TI - Solution-Phase Synthesis of Platinum Nanoparticle-Decorated Metal-Organic
Framework Hybrid Nanomaterials as Biomimetic Nanoenzymes for Biosensing
Applications.
AB - The synthesis of nanomaterials with specific properties and functions as
biomimetic nanoenzymes has attracted extensive attention in the past decades due
to their great potential to substitute natural enzymes. Herein, a facile and
simple method for the preparation of platinum nanoparticle (PtNP)-decorated two
dimensional metal-organic framework (MOF) nanocomposites was developed. A ligand
with heme-like structure, Fe(III) tetra(4-carboxyphenyl)porphine chloride
(TCPP(Fe)), was applied to synthesize MOF nanosheets (denoted as Cu-TCPP(Fe)
nanosheets) in high yield. Ultrathin Cu-TCPP(Fe) nanosheets with thickness less
than 10 nm were used as a novel template for the growth of ultrasmall and uniform
PtNPs. Significantly, the obtained hybrid nanomaterials (PtNPs/Cu-TCPP(Fe) hybrid
nanosheets) exhibit enhanced peroxidase-like activity compared to PtNPs, Cu
TCPP(Fe) nanosheets, and the physical mixture of both due to the synergistic
effect. On account of the excellent peroxidase-like activity of PtNPs/Cu-TCPP(Fe)
hybrid nanosheets, we established a colorimetric method for sensitive and rapid
detection of hydrogen peroxide. Furthermore, by combining with glucose oxidase, a
cascade colorimetric method was established to further detect glucose with
excellent sensitivity and selectivity.
PMID- 29956535
TI - Porous Graphene-Confined Fe-K as Highly Efficient Catalyst for CO2 Direct
Hydrogenation to Light Olefins.
AB - We devised iron-based catalysts with honeycomb-structured graphene (HSG) as the
support and potassium as the promoter for CO2 direct hydrogenation to light
olefins (CO2-FTO). Over the optimal FeK1.5/HSG catalyst, the iron time yield of
light olefins amounted to 73 MUmolCO2 gFe-1 s-1 with high selectivity of 59%. No
obvious deactivation occurred within 120 h on stream. The excellent catalytic
performance is attributed to the confinement effect of the porous HSG on the
sintering of the active sites and the promotion effect of potassium on the
activation of inert CO2 and the formation of iron carbide active for CO2-FTO.
PMID- 29956536
TI - Electrochemical Evaluation of the Number of Au Atoms in Polymeric Gold Thiolates
by Single Particle Collisions.
AB - Polymeric gold thiolates, [Au(I)SR] n, are common synthetic intermediate
precursors of gold nanoclusters and larger nanoparticles. The size and dispersity
of the precursors strongly influence the properties of the synthesis products.
Evaluating the size of the precursors is not straightforward because they are
irregularly shaped (nonspherical) and hard to isolate from solution. Herein, we
propose an effective method for determining the number of Au atoms in polymeric
thiolate particles from current transients resulting from single precursor
collisions, where individual [Au(I)SR] n species are electrochemically reduced at
the collector ultramicroelectrode. The developed approach can lead to a better
control over the mean size and dispersity of colloidal metal nanoclusters and
nanoparticles.
PMID- 29956537
TI - A Polymer Dots-Based Photoelectrochemical pH Sensor: Simplicity, High
Sensitivity, and Broad-Range pH Measurement.
AB - This work reported the photoelectrochemical (PEC) pH sensor for sensitive and
broad-range pH measurement on the basis of semiconducting polymer dots (Pdots).
The sensor was fabricated by immobilizing Pdots onto the surface of indium tin
oxide (ITO). Experimental results revealed that the carboxylic acid groups of
Pdots were sensitive to pH variation, which could result in conformational
changes and further diffusion of carriers. Besides, different pH value could
change the redox properties of the Pdots, and the photocurrent response was hence
altered by the carriers produced on the Pdots. Further results demonstrated that
the developed sensor exhibited variable photocurrent sensitively by responding to
different pH values. This pH sensor is of high sensitivity, stability, and
reversibility, which provides a bright prospect for future pH measurements in the
bioanalytical field.
PMID- 29956538
TI - Facile Two-Step Strategy for the Construction of a Mechanically Stable Three
Dimensional Superhydrophobic Structure for Continuous Oil-Water Separation.
AB - It has been a big challenge to separate oil slicks from oil-polluted water
sources efficiently and in an environmentally friendly way. Three-dimensional
(3D) hydrophobic and superoleophilic materials have great potential in water
separation continually. In this study, we developed a facile two-step strategy
for fixing functionalized nanoparticles on 3D complex macroscopic surfaces. By
using commercial glue to immobilize different types of nanoparticles on the
surfaces of various 3D objects, superhydrophobic copper foam, cotton wool, and
polyurethane (PU) sponge with strong stability and excellent performance were
prepared. Owing to flexible fixing with the glue, the prepared PU sponge remained
superhydrophobic after 950 mechanical compression cycles, 250 cycles of
absorption/squeezing, or soaking in n-dodecane for 60 h. The prepared PU sponge
was applied to the rapid absorption of clean oil on a water surface, and the
feasibility of separating mixed oil through capillary separation of cavernous
bodies was examined. Furthermore, the method for loading nanoparticles onto a 3D
structure can be used with many self-cleaning, flexible electrodes and catalysts.
PMID- 29956539
TI - Unusual Reduction Mechanism of Copper in Cysteine-Rich Environment.
AB - Copper-cysteine interactions play an important role in Biology and herein we used
the copper-substituted rubredoxin (Cu-Rd) from Desulfovibrio gigas to gain
further insights into the copper-cysteine redox chemistry. EPR spectroscopy
results are consistent with Cu-Rd harboring a CuII center in a sulfur-rich
coordination, in a distorted tetrahedral structure ( g?,? = 2.183 and 2.032 and
A?,? = 76.4 * 10-4 and 12 * 10-4 cm-1). In Cu-Rd, two oxidation states at Cu
center (CuII and CuI) are associated with Cys oxidation-reduction, alternating in
the redox cycle, as pointed by electrochemical studies that suggest internal
geometry rearrangements associated with the electron transfer processes. The
midpoint potential of [CuI(S-Cys)2(Cys-S-S-Cys)]/[CuII(S-Cys)4] redox couple was
found to be -0.15 V vs NHE showing a large separation of cathodic and anodic
peaks potential (Delta Ep = 0.575 V). Interestingly, sulfur-rich CuII-Rd is
highly stable under argon in dark conditions, which is thermodynamically
unfavorable to Cu-thiol autoreduction. The reduction of copper and concomitant
oxidation of Cys can both undergo two possible pathways: oxidative as well as
photochemical. Under O2, CuII plays the role of the electron carrier from one Cys
to O2 followed by internal geometry rearrangement at the Cu site, which
facilitates reduction at Cu-center to yield CuI(S-Cys)2(Cys-S-S-Cys).
Photoinduced (irradiated at lambdaex = 280 nm) reduction of the CuII center is
observed by UV-visible photolysis (above 300 nm all bands disappeared) and
tryptophan fluorescence (~335 nm peak enhanced) experiments. In both pathways,
geometry reorganization plays an important role in copper reduction yielding an
energetically compatible donor-acceptor system. This model system provides
unusual stability and redox chemistry rather than the universal Cu-thiol auto
redox chemistry in cysteine-rich copper complexes.
PMID- 29956540
TI - Less-Lead Control toward Highly Efficient Formamidinium-Based Perovskite Light
Emitting Diodes.
AB - A formamidinium (FA)-based perovskite is an ideal option for the potential
efficient light-emitting diode (LED) in view of its high tolerance factor closer
to 1. In this work, FA cation-based perovskite nanocrystals FA0.8Cs0.2Pb xBr3 ( x
= 1.0, 0.8, 0.7, and 0.6) are fabricated with stoichiometric modification. The
adoption of less-lead precursor is confirmed to be a feasible and effective
approach in inhibiting nonradiative recombination by diminishing the presence of
uncoordinated metallic Pb atoms. Note that the subsequent devices require the
optimized lead ratio for an optimum behavior, a clear influence of Pb ratio on a
perovskite LED has been established. No surprisingly, the less-lead perovskites
exert positive roles on the perovskite LED performance, not only in terms of
efficiency but also in stability. With an optimized composition
FA0.8Cs0.2Pb0.7Br3, the perovskite LED displays the prominent performance with a
current efficiency of 28.61 cd A-1, about 11-fold improvement than the previous
best record of pure FA-based perovskite. Additionally, the perovskite device
degradation can be mitigated under operating conditions by properly altering
precursor stoichiometry, which can be attributed to the hydrogen reaction under
moisture-induced ambient. The stoichiometric optimization of the metal Pb in the
perovskite is an important strategy on the road to the further development of
perovskite LEDs.
PMID- 29956541
TI - Bronsted Basicity in Metal-Organic Framework-808 and Its Application in Base-Free
Catalysis.
AB - The Bronsted basicity in activated metal-organic framework-808 (hereinafter
denoted as MOF-808a) was confirmed by the analyses of CO2-TPD-MS, in situ DRIFTS,
and acid-base titration. MOF-808a exhibited efficient recyclable catalytic
activities for Heck coupling and oxidation of alcohol as a one-pot tandem
reaction in base-free catalysis. It is the first evidence of the Bronsted
basicity in zirconium metal-organic frameworks (Zr-MOFs) and gave rise to a new
opportunity to extend the catalytic application of Zr-MOFs.
PMID- 29956542
TI - [2 + 2 + 2]-Cycloaddition Reactions Using Immobilized Alkynes. A Proof of Concept
for an Integral Use of the Outcoming Products in Solid-Phase Synthetic
Methodologies.
AB - The transition-metal-catalyzed [2 + 2 + 2]-cycloaddition of alkynes has become a
powerful atom-economical strategy for aromatic ring construction. Unfortunately,
the control of the stereo-, regio-, and chemoselectivity of these processes is
usually challenging, and these reactions can potentially lead to complex unuseful
mixtures. While solid-phase chemistry has proven to be a successful tool for
decreasing the number of cycloadducts formed and for facilitating the
purification step, an integral use of the outcoming products in this complex
reaction is described herein. By using an immobilized monoalkyne, the transition
metal-catalyzed [2 + 2 + 2]-cycloaddition with soluble 1,6-diyne-esters led to
the simultaneous preparation of soluble and solid-supported phthalides, showing a
new way to benefit from solid-phase synthetic methodologies.
PMID- 29956543
TI - Molecular Dynamics and Quantum Chemical Approach for the Estimation of an
Intramolecular Hydrogen Bond Strength in Okadaic Acid.
AB - We have evaluated the strength of intramolecular hydrogen bond in a protein based
on molecular dynamics and quantum chemical calculation. To estimate the
intramolecular hydrogen bond strength in okadaic acid (OA), we analyzed the
influence of solvent and protonation states on the hydrogen bond and the entire
structure. We performed molecular dynamics calculation and analyzed the strength
of the hydrogen bond by measuring bond length and bond angle. The stable
structure differs depending on the kind of solvent used and the protonation state
of OA. Using the mean interaction energy from the quantum chemical calculation,
hydrogen bond length and angle were investigated against bond energy. Although
dielectric constant slightly depends on bond energy, the estimation of the
intramolecular hydrogen bond strength in OA is possible even in a protein
environment. The Coulomb interaction between OA and surrounding arginine produced
a more negatively charged O1 in OA. The hydrogen bond energy in the deprotonated
state is larger than that in the protonated state.
PMID- 29956544
TI - Substantial Impact of Charge on Electrochemical Reactions of Two-Dimensional
Materials.
AB - Two-dimensional (2D) materials have attracted great interest in catalyzing
electrochemical reactions such as water splitting, oxygen reduction, and carbon
dioxide reduction. Quantum mechanical simulations have been extensively employed
to study the catalytic mechanisms. These calculations typically assume that the
catalyst is charge neutral for computational simplicity; however, in reality, the
catalyst is usually charged to match its Fermi level with the applied electrode
potential. These contradictions urge an evaluation of the charge effects. Here,
using the example of hydrogen adsorption on the common 2D electrocatalysts (N
doped graphene and MoS2) and 3D metal catalysts, and employing the grand
canonical density functional theory, we show that the charge on 2D materials can
have a much stronger impact on the electrochemical reaction than the charge on 3D
metals (the reaction energy can differ by >1 eV after including the charge
effects). This arises from the charge-induced change in the occupation of
electronic states, which is more significant for 2D materials due to their
limited density of states. Our work provides a fundamental understanding of the
charge effects in 2D materials, calls for re-evaluation of the previously
suggested mechanisms by including the overlooked charge effects, and offers
practical guidelines for designing 2D catalysts.
PMID- 29956545
TI - TCFH-NMI: Direct Access to N-Acyl Imidazoliums for Challenging Amide Bond
Formations.
AB - Challenging couplings of hindered carboxylic acids with non-nucleophilic amines
to form amide bonds can be accomplished in high yields, and in many cases, with
complete retention of the adjacent stereogenic centers using the combination of
N, N, N', N'-tetramethylchloroformamidinium hexafluorophosphate (TCFH) and N
methylimidazole (NMI). This method allows for in situ generation of highly
reactive acyl imidazolium ions, which have been demonstrated to be intermediates
in the reaction. The reagent delivers high reactivity similar to acid chlorides
with the ease of use of modern uronium reagents.
PMID- 29956546
TI - Modus operandi of COMPASS/MLL epigenetic writers in the mammalian genome.
PMID- 29956547
TI - Time- and sex-dependent associations between prenatal alcohol exposure and
placental global DNA methylation.
AB - AIM: Epigenetic changes, in particular in the placenta, may mediate the effects
of prenatal alcohol exposure (PAE) on children's health. We examined the
relationship between PAE patterns, based on dose and timing, and placental global
DNA methylation. METHODS: Using linear regression analysis, we examined the
association between different PAE categories and placental global DNA methylation
(n = 187), using the proxy measure of Alu-interspersed repeats. RESULTS:
Following adjustment for important covariates, we found no evidence of an
association between PAE and placental global DNA methylation overall. However,
when stratifying by newborn sex, PAE throughout pregnancy was associated with
higher placental global DNA methylation (1.5%; p = 0.01) of male newborns.
CONCLUSION: PAE may have sex-specific effects on placental global DNA methylation
if alcohol is consumed throughout pregnancy.
PMID- 29956549
TI - Are we doing enough to tackle preventable causes of cancer: an interview with
Professor Linda Bauld.
AB - Linda Bauld speaks to Roshaine Wijayatunga, Managing Commissioning Editor. Linda
Bauld is Professor of Health Policy, Director of the Institute of Social
Marketing and Dean of Research Impact at the University of Stirling. She also
holds the CRUK/BUPA Chair in Behavioral Research for Cancer Prevention at Cancer
Research UK and is Deputy Director of the UK Center for Tobacco and Alcohol
Studies, a UKCRC Center for Public Health Excellence covering 13 Universities.
She is a behavioral scientist with a particular interest in interventions,
services and policies that can prevent chronic disease including cancer. She is a
former scientific advisor to the UK government on Tobacco Control, President of
the Society for Research on Nicotine and Tobacco, Europe and a Fellow of the
Royal College of Physicians of Edinburgh.
PMID- 29956548
TI - Clinical features and psychological aspects of the decision-making process in
stage I testicular germ cell tumors.
AB - Testicular germ cell tumors (TGCTs) are the most prevalent malignancies in young
Caucasian men. Clinical stage I (CSI) TGCTs present the highest cure rate and
treatment options after orchiectomy depend on histology and risk factors.
Nevertheless, the management of CSI TGCTs is controversial due to the
availability of multiple treatments and the lack of randomized trials. An
integrated multidisciplinary approach that includes clinicians (surgeons,
radiotherapists and oncologists) and psychologists is crucial to maximize the
patients' compliance and must be acknowledged with appropriate tools. The aim of
our work is to review the oncological and psychological aspects of the decision
making process, discussing the fundamental role of the patient involvement in the
personalized management of CSI TGCTs.
PMID- 29956550
TI - How to choose medicinally more valuable yogurt products for the prevention of
heart disease and colorectal cancer.
PMID- 29956551
TI - Another brick in the wall: The impact of ticagrelor use on the incidence of
stroke in a large registry.
PMID- 29956552
TI - PAIN(S) relievers for medicinal chemists: how computational methods can assist in
hit evaluation.
PMID- 29956553
TI - Editor's presentation.
PMID- 29956554
TI - Left atrial thrombus resolution in non-valvular atrial fibrillation or flutter:
Biomarker substudy results from a prospective study with rivaroxaban (X-TRA).
AB - BACKGROUND: Non-vitamin K antagonist oral anticoagulants including rivaroxaban
are widely used for stroke prevention in patients with atrial fibrillation (AF).
We investigated the relationship between plasma biomarkers (indicative of
thrombogenesis, fibrinolysis and inflammation) and left atrial thrombus
resolution after rivaroxaban treatment. METHODS: This was an ancillary analysis
of the X-TRA study, which was a prospective interventional study evaluating the
use of rivaroxaban for left atrial/left atrial appendage (LA/LAA) thrombus
resolution in AF patients. We assessed various biomarkers of
thrombogenesis/fibrinolysis [D-dimer, plasminogen activator inhibitor-1 (PAI-1),
prothrombin fragment 1 + 2 (F1,2), thrombin-antithrombin (TAT) complexes, von
Willebrand factor (vWF)] and inflammation [high-sensitivity interleukin-6 (hsIL
6), and high-sensitivity C-reactive protein (hsCRP)], measured at baseline and
after 6 weeks' of rivaroxaban treatment. RESULTS: There were significant
decreases in the mean levels of hsCRP, D-dimer, vWF, and TAT from baseline to end
of treatment with rivaroxaban. Although none of the thrombogenesis/fibrinolysis
biomarkers showed a significant relationship with thrombus resolution, high
inflammatory biomarkers at baseline were significantly associated with an
increased chance of the thrombus being completely resolved (hsIL-6) or
reduced/resolved (hsCRP). CONCLUSIONS: Biomarkers of inflammation are
significantly associated with LA/LAA thrombus outcomes in AF patients
prospectively treated with rivaroxaban.
PMID- 29956555
TI - Phylogenetic analysis and genetic structure of the seahorse, Hippocampus fuscus
from the Arabian and Red Sea based on mitochondrial DNA sequences.
AB - The unique body morphology and specialized life history traits make seahorses
excellent flagship species for many issues in marine conservation and biological
evolution. In this study, the complete mitochondrial genome of Hippocampus fuscus
was determined. Phylogenetic analyses showed that H. fuscus had a close genetic
relationship to Hippocampus reidi, which give us a new insight into the
speciation and dispersal among seahorse genus. A total of 843 base pairs of
cytochrome b (Cytb) gene and a 646 base pairs of cytochrome oxidase I (COI) gene
were obtained from 36 H. fuscus and 26 H. reidi from three populations.
Population genetic analysis revealed a relatively high genetic diversity across
the populations of H. fuscus compared with H. reidi. Neighbour-joining (NJ) tree
of COI and Cytb gene sequences showed that H. fuscus haplotypes formed one
cluster. The result of median-joining network of haplotypes based on COI and Cytb
indicated a lack of structure in populations of H. fuscus. This study addressed
the information about the evolution history and genetic structure of an Arabian
seahorse H. fuscus, which provides insight into the genetic conservation and
sustainable management for this species.
PMID- 29956557
TI - Effectiveness and feasibility of Socratic feedback to increase awareness of
deficits in patients with acquired brain injury: Four single-case experimental
design (SCED) studies.
AB - OBJECTIVE: To investigate the effectiveness and feasibility of a Socratic
feedback programme to improve awareness of deficits in patients with acquired
brain injury (ABI). SETTING: Rehabilitation centre. PARTICIPANTS: Four patients
with ABI with awareness problems. DESIGN: A series of single-case experimental
design studies with random intervention starting points (A-B + maintenance
design). MAIN MEASURES: Rate of trainer-feedback and self-control behaviour on
everyday tasks, patient competency rating scale (PCRS), self-regulating skills
interview (SRSI), hospital anxiety and depression scale. RESULTS: All patients
needed less trainer feedback, the change was significant in 3 out of 4. One
patient increased in overt self-corrective behaviour. SRSI performance increased
in all patients (medium to strong effect size), and PCRS performance increased in
two patients (medium and strong effect size). Mood and anxiety levels were
elevated in one patient at the beginning of the training and decreased to normal
levels at the end of the training. The feasibility of the programme was scored 9
out of 10. CONCLUSIONS: The Socratic feedback method is a promising intervention
for improving awareness of deficits in patients with ABI. Controlled studies with
larger populations are needed to draw more solid conclusions about the effect of
this method.
PMID- 29956556
TI - Comparison of conventional and advanced in vitro models in the toxicity testing
of nanoparticles.
AB - Humans are exposed to a wide variety of nanoparticles (NPs) present in the
environment, in consumer, health and medical products, and in food. Conventional
cytotoxicity testing compared to animal testing is less expensive, faster and
avoids ethical problems at the expense of a lower predictive value. New cellular
models and exposure conditions have been developed to overcome the limitations of
conventional cell culture and obtain more predictive data. The use of three
dimensional culture, co-culture and inclusion of mechanical stimulation can
provide physiologically more relevant culture conditions. These systems are
particularly relevant for oral, respiratory and intravenous exposure to NPs and
it may be assumed that physiologically relevant application of the NPs can
improve the predictive value of in vitro testing. Various groups have used
advanced culture and exposure systems, but few direct comparisons between data
from conventional cultures and from advanced systems exist. In silico models may
present another option to predict human health risk by NPs without using animal
studies. In the absence of validation, the question whether these alternative
models provide more predictive data than conventional testing remains elusive.
PMID- 29956558
TI - Advance care planning: A systematic review about experiences of patients with a
life-threatening or life-limiting illness.
AB - BACKGROUND: Advance care planning is seen as an important strategy to improve end
of-life communication and the quality of life of patients and their relatives.
However, the frequency of advance care planning conversations in practice remains
low. In-depth understanding of patients' experiences with advance care planning
might provide clues to optimise its value to patients and improve implementation.
AIM: To synthesise and describe the research findings on the experiences with
advance care planning of patients with a life-threatening or life-limiting
illness. DESIGN: A systematic literature review, using an iterative search
strategy. A thematic synthesis was conducted and was supported by NVivo 11. DATA
SOURCES: The search was performed in MEDLINE, Embase, PsycINFO and CINAHL on 7
November 2016. RESULTS: Of the 3555 articles found, 20 were included. We
identified three themes in patients' experiences with advance care planning.
'Ambivalence' refers to patients simultaneously experiencing benefits from
advance care planning as well as unpleasant feelings. 'Readiness' for advance
care planning is a necessary prerequisite for taking up its benefits but can also
be promoted by the process of advance care planning itself. 'Openness' refers to
patients' need to feel comfortable in being open about their preferences for
future care towards relevant others. CONCLUSION: Although participation in
advance care planning can be accompanied by unpleasant feelings, many patients
reported benefits of advance care planning as well. This suggests a need for
advance care planning to be personalised in a form which is both feasible and
relevant at moments suitable for the individual patient.
PMID- 29956560
TI - Highly stable gold nanoparticles green-synthesized by upcycling cartilage waste
extract from yellow-nose skate (Dipturus chilensis) and evaluation of its
cytotoxicity, haemocompatibility and antioxidant activity.
AB - Skate (Dipturus chilensis) cartilage extract was utilized as a green reducing
agent for the synthesis of spherical gold nanoparticles with an average size of
16.7 +/- 0.2 nm. The gold nanoparticle solution showed a surface plasmon
resonance at 543 nm with a wine-red colour. A strong X-ray diffraction pattern
and clear lattice structure in high-resolution transmission electron microscopy
indicated a face-centred cubic structure of the gold nanoparticles. The gold
nanoparticles retained excellent colloidal stability. Gold nanoparticles showed
strong antioxidant activity in terms of 2,2-diphenyl-1-picrylhydrazyl radical
scavenging activity. In vitro cytotoxicity was observed for seven cancer cells
assessed by the water-soluble tetrazolium assay. Among the seven cancer cells,
the highest cytotoxicity was observed for MDA-MB-231 (human breast adenocarcinoma
cell) followed by HeLa (human epithelial cervix adenocarcinoma cell) and lastly
by HT-29 (human colorectal adenocarcinoma cell). Furthermore, gold nanoparticles
showed excellent haemocompatibility, indicating the possibility of their use as a
future nanomedicine. These results strongly suggest that gold nanoparticles green
synthesized by upcycling skate cartilage waste extract will be valuable carriers
or vehicles for the delivery of drugs or bioactive molecules, such as anti-cancer
agents, for the treatment of cancers.
PMID- 29956559
TI - The influence of oxygen delivery during cardiopulmonary bypass on the incidence
of delirium in CABG patients; a retrospective study.
AB - INTRODUCTION:: Postoperative delirium is the most common neurological
complication of cardiac surgery. Hypoxia has been shown to increase the risk of
postoperative delirium. The possibility to continuously monitor oxygen delivery
(DO2) during cardiopulmonary bypass (CPB) offers an adequate approximation of the
oxygen status in a patient. This study investigates the role of oxygen delivery
during cardiopulmonary bypass in the incidence of postoperative delirium.
METHODS:: Three hundred and fifty-seven adult patients who underwent normothermic
coronary artery bypass grafting (CABG) surgery were included in this
retrospective study. The nadir indexed DO2 (DO2i) value on bypass, the total time
under the critical DO2i level and the area under the curve (AUC) for critical
DO2i were determined. Delirium was identified by the postoperative administration
of haloperidol. RESULTS:: The mean nadir DO2i significantly differed, comparing
the group of patients with postoperative delirium to the group without.
Multivariate analysis only identified age, pre-existing cognitive impairment,
preoperative kidney dysfunction and cross-clamp time as independent risk factors
for delirium. The results also indicated that patients of older age were more
sensitive to a declined DO2i. CONCLUSION:: A low DO2i during cardiopulmonary
bypass is significantly associated with the incidence of postoperative delirium
in CABG patients. However, the role of DO2 as an independent predictor of
delirium could not be proven.
PMID- 29956561
TI - Physiotherapy practice in pulmonary hypertension: physiotherapist and patient
perspectives.
AB - Pulmonary hypertension (PH) is a life-limiting disease affecting circulation to
the lungs. The primary symptom of PH is breathlessness, yet research has shown
that patients with PH can exercise safely and can benefit from exercise to
improve exercise capacity and maintain quality of life. This study aimed to
investigate the nature of physiotherapy delivered to patients with PH in the UK.
This was a two-phase sequential, exploratory, mixed-methods study. Interviews
were conducted with seven lead physiotherapists at specialist pulmonary
hypertension centers and three patients. Survey data came from 63
physiotherapists caring for patients with PH in specialist and non-specialist
settings. The findings from the two phases were triangulated and analyzed.
Findings showed that physiotherapists and patients see the benefit and potential
of physical activity for patients with PH to maintain functional wellbeing.
However, current physiotherapy provision focuses on acute inpatient care and
planning for discharge and is not therefore aligned with research evidence and
clinical guidelines. In the absence of inpatient rehabilitation facilities,
physiotherapists will occasionally access existing community services, e.g.
pulmonary rehabilitation; however, specialist knowledge of this rare condition
can be lacking in local services. There is aspiration among physiotherapists and
patients for a new approach which supports patients from diagnosis with PH to end
of life. This includes promoting and delivering rehabilitation and exercise
interventions to achieve better health outcomes, in line with patient needs.
Treatment would be commissioned and delivered within existing national health
systems with physiotherapists developing strategies for health improvement.
PMID- 29956562
TI - Neuro-oncology perspective of treatment options in metastatic breast cancer.
AB - Breast cancer (BC) is a heterogeneous disease. Different subtypes of BC exhibit a
peculiar natural history, metastatic potential and outcome. Stereotactic
radiosurgery is the most used treatment for brain metastases (BM), while surgery
is reserved for large and symptomatic lesions. Whole-brain radiotherapy is
employed in multiple BM not amendable to radiosurgery or surgery, and it is not
employed any more following local treatments of a limited number of BM. A
critical issue is the distinction from pseudoprogression or radionecrosis, and
tumor regrowth. Considering the increase of long-term survivors after combined or
novel treatments for BM, cognitive dysfunctions following whole-brain
radiotherapy represent an issue of utmost importance. Neuroprotective drugs and
innovative radiotherapy techniques are being investigated to reduce this risk of
cognitive sequelae. Leptomeningeal disease represents a devastating complication,
either alone or in association to BM, thus targeted therapies are employed in
HER2-positive BC brain and leptomeningeal metastases.
PMID- 29956563
TI - Unique static discharge events on two CentriMag(r) (2nd Gen) ECMO patients
causing console failure.
AB - The use of ECMO for cardiovascular support continues to increase in the United
States and around the world. It is not a benign endeavor as serious complications
may occur. We present our experience of two second generation CentriMag(r)
(Abbott formerly Thoratec Inc.) console failures that occurred while transporting
the patients to other areas of the hospital. In each incident, the patients were
immediately placed on back-up units and the transport continued. No patient
complications could be attributed to the failures. An investigation by Abbott
engineers traced the failure to a static build-up and discharge caused by a non
manufacturer-approved metal rod that was utilized to mount the external monitor.
The static discharge caused a disruption of electrical continuity between the
control system and the motor, stopping the motor as well as the monitoring
system. Removal of the mounting rod prevented replication of the situation in the
lab. We have removed the rod from our clinical units and have not experienced any
other pump failures.
PMID- 29956564
TI - Development and psychometric properties of the Self-efficacy for Mindfulness
Meditation Practice scale.
AB - This study aimed to develop a self-efficacy measure for mindfulness meditation
practice (Self-efficacy for Mindfulness Meditation Practice scale). The scale was
developed through a process of expert consensus, cognitive interviewing, and
evaluation among 199 mindfulness meditation practitioners who completed an online
survey. The 9-item Self-efficacy for Mindfulness Meditation Practice scale was
unidimensional with three subconstructs of attention, compassion, and emotion.
The omega hierarchical coefficient for the total scale was 0.78, and test-retest
reliability was intraclass correlation coefficient = 0.85 (95% confidence
interval: 0.80, 0.89). This study provides preliminary evidence that Self
Efficacy for Mindfulness Meditation Practice scale is a reliable and valid
measure of self-efficacy for mindfulness meditation practice.
PMID- 29956565
TI - Estimating the osteolysis-free life of a total hip prosthesis depending on the
linear wear rate and head size.
AB - We present a model to estimate the osteolysis-free life of total hip
arthroplasty, depending on linear wear rate and femoral head size. An estimate of
the radiologic osteolysis threshold was calculated, which was based on volumetric
wear. The osteolysis-free life of the cup was estimated from the quotient of the
osteolysis threshold and volumetric wear rate, which was calculated from the
linear wear rate. The impact of the direction of linear wear was determined by
sensitivity analysis. From our review, we calculated a weighted mean polyethylene
volume of approximately 670 mm3 as osteolysis threshold. Osteolysis-free life of
less than 20 years was estimated for linear wear rates of 50 um/year for head
sizes of 32 mm or more, or for linear wear rates of 100 um/year for any head
size. For head sizes of 36 and 40 mm with a linear wear rate of 50 um/year, the
osteolysis-free period is estimated to be only 14.10 and 11.42 years,
respectively. Sensitivity analysis showed reasonably robust results. With the aim
of osteolysis-free life of more than 20 years, our study presents a viable model
to determine maximum possible head size for articulations. Osteolysis-free period
for 36 and 40 mm head sizes are far too low for conventional polyethylenes. As
the threshold wear volume for highly crosslinked polyethylene is, as of yet,
unknown, more research is warranted before our model can be generalized to XLPE.
PMID- 29956566
TI - Association of five genetic variations in DNMT1 and DNMT3A with gastric cancer in
a Chinese population.
AB - AIM: To determine whether genetic variations in DNMT1 and DNMT3A could be
associated with gastric cancer risk. MATERIALS & METHODS: A total of 466 patients
and 452 healthy controls were enrolled in this study. Genotypes were examined by
using the Sequenom MassARRAY platform. RESULTS: No significant differences in the
distribution frequencies were observed between the groups. However, subgroup
analysis revealed that, in the group aged <=60 years, DNMT3A rs13420827 was
associated with reduced gastric cancer risk, and that carrier of GC/GG genotype
was associated with reduced risk of gastric cancer with low differentiation or at
the T3-T4 stage. CONCLUSION: This study suggests that five genetic variations of
interest in DNMT1 and DNMT3A are not associated with the presence of gastric
cancer, but that rs13420827 may contribute to the gastric cancer risk for those
younger individuals, the risk of which may be influenced by the characteristics
of tumor.
PMID- 29956567
TI - Effect of inflow cannula side-hole number on drainage flow characteristics: flow
dynamic analysis using numerical simulation.
AB - BACKGROUND:: Venous drainage in cardiopulmonary bypass is a very important factor
for safe cardiac surgery. However, the ideal shape of venous drainage cannula has
not been determined. In the present study, we evaluated the effect of side-hole
number under fixed total area and venous drainage flow to elucidate the effect of
increasing the side-hole numbers. METHOD:: Computed simulation of venous drainage
was performed. Cannulas were divided into six models: an end-hole model (EH) and
models containing four (4SH), six (6SH), eight (8SH), 10 (10SH) or 12 side-holes
(12SH). Total orifice area of the side-holes was fixed to 120 mm2 on each side
hole cannula. The end-hole orifice area was 36.3 mm2. The total area of the side
holes was kept constant when the number of side-holes was increased. RESULT:: The
mean venous drainage flow rate of the EH, 4SH, 6SH, 8SH, 10SH and 12SH was 2.57,
2.52, 2.51, 2.50, 2.49, 2.41 L/min, respectively. The mean flow rate decreased in
accordance with the increased number of side-holes. CONCLUSION:: We speculate
that flow separation at the most proximal site of the side-hole induces
stagnation of flow and induces energy loss. This flow separation may hamper the
main stream from the end-hole inlet, which is most effective with low shear
stress. The EH cannula was associated with the best flow rate and flow profile.
However, by increasing side-hole numbers, flow separation occurs on each side
hole, resulting in more energy loss than the EH cannula and flow rate reduction.
PMID- 29956568
TI - Patient empowerment, what does it mean for adults in the advanced stages of a
life-limiting illness: A systematic review using critical interpretive synthesis.
AB - BACKGROUND: Patient empowerment, defined as 'a process through which people gain
greater control over decisions and actions affecting their health' (World Health
Organization) is a key theme within global health and social care strategies. The
benefits of incorporating empowerment strategies in care are well documented, but
little is known about their application or impact for patients with advanced,
life-limiting illness(s). AIM: To identify and synthesise the international
evidence on patient empowerment for adults with advanced, life-limiting
illness(s). DESIGN: Systematic review (PROSPERO no. 46113) with critical
interpretive synthesis methodology. DATA SOURCES: Five databases (MEDLINE,
Embase, CINHAL, PsycINFO and Cochrane) were searched from inception to March
2018. Grey literature and reference list/citation searches of included papers
were undertaken. INCLUSION CRITERIA: empirical research involving patients with
advanced life-limiting illness including descriptions of, or references to,
patient empowerment within the study results. RESULTS: In all, 13 papers met
inclusion criteria. Two qualitative studies explored patient empowerment as a
study objective. Six papers evaluated interventions, referencing patient
empowerment as an incidental outcome. The following themes were identified from
the interpretive synthesis: self-identity, personalised knowledge in theory and
practice, negotiating personal and healthcare relationships, acknowledgement of
terminal illness, and navigating continued losses. CONCLUSION: There are features
of empowerment, for patients with advanced life-limiting illness distinct to
those of other patient groups. Greater efforts should be made to progress the
empowerment of patients nearing the end of their lives. We propose that the
identified themes may provide a useful starting point to guide the assessment of
existing or planned services and inform future research.
PMID- 29956569
TI - Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of
cerebral infarction.
AB - Cerebral infarction is with poorer prognosis and high rates of mortality. After
cerebral infarction, the promoting angiogenesis can accelerate the recovery of
neurological function. Long non-coding RNA (LncRNA) maternally expressed gene 3
(Meg3) was overexpressed in cerebral infarction area and the knockdown of Meg3
promotes neovascularization and improves nerve function. In this study, we
fabricated a nano-polymer wrapped Meg3 short hairpin RNA (ShRNA) plasmid to
knockdown Meg3 and conjugated with OX26 antibody (MPO) to realize the brain
targeting for the treatment of cerebral infarction. The MPO particle size was 103
+/- 11 nm (PDI = 0.27) detected by dynamic light scattering (DLS) and the zeta
potential of MPO was -32 mV. MPO achieved brain microvascular endothelial cell
(BMEC) targeting and enhanced endothelial cells migration (p < .05), and tube
formation (p < .05) in vitro. MPO realized brain tissue target, reduced the
volume of cerebral infarction (p < .05) detected by TTC staining, increased
capillary density through the HE staining and increased cerebral cortex micro
vessel through immunofluorescence method in vivo. The angiogenesis associated
genes Vegfa, and Vegfr2 were upregulated after the treatment of MPO, compared
with Meg3 or control plasmid treated group. This study suggested that MPO could
achieve brain target and significantly promoted angiogenesis and became a new
treatment method for cerebral infarction.
PMID- 29956570
TI - Physostigmine is superior to non-antidote therapy in the management of
antimuscarinic delirium: a prospective study from a regional poison center.
AB - CONTEXT: Poison centers (PCs) frequently manage patients with antimuscarinic
delirium. However, controversy surrounds the antidotal use of physostigmine for
its treatment. The aim of this study was to prospectively investigate
physostigmine versus non-antidote therapy for the management of antimuscarinic
delirium in a single regional PC. METHODS: This was a prospective observational
analysis of patients diagnosed with antimuscarinic delirium and treated in
consultation with a regional PC. Certified Specialists in Poison Information
(CSPIs) use a clinical guideline to recommend the use of physostigmine. Using a
previously derived altered mental status score, we quantified the rate of
delirium improvement with physostigmine compared to non-antidote therapy two
hours after initial patient identification. We also recorded adverse events
(defined a priori as bradycardia, vomiting, seizures) and resource utilization
(intubation and physical restraint). RESULTS: We identified 245 patients and
included 154 in the analysis. The most common exposure classes were
antihistamines (68%), analgesics (19%), and antipsychotics (19%). CSPIs
recommended physostigmine in 81% (125) of cases and the treatment team
administered it in 37% (57) of these. We observed delirium control in 79% of
patients who received physostigmine versus 36% of those who did not. The odds of
delirium control were six times greater for patients receiving physostigmine than
for patients treated with non-antidote therapy (OR 6.6). Adverse events were rare
and did not differ significantly between the groups. Physostigmine was not
associated with changes in the incidence of intubation or restraint. CONCLUSIONS:
This study provides further evidence of both the safety and efficacy of
physostigmine in the treatment of antimuscarinic delirium.
PMID- 29956572
TI - General practitioners' and nurses' views on medication reviews and potentially
inappropriate medicines in elderly patients - a qualitative study of reports by
educating pharmacists.
AB - OBJECTIVE: The aim with this study was to understand more about how general
practitioners (GPs) and nurses in primary care experience their work with
medication reviews in elderly patients. DESIGN: This qualitative study was nested
within a cluster randomised trial and analysed narrative and unstructured diaries
written by two pharmacists who performed academic detailing, i.e. educational
outreach visits in primary care. The educational sessions dealt with potentially
inappropriate medicines, and stimulated interprofessional dialogue in relation to
medication reviews. The purpose of the diaries was to document and structure the
pedagogical process of academic detailing and contained quotes from 194 GP and
113 nurse participants in the sessions, and the pharmacists' reflections. The
data was explored using thematic analysis. SETTING: Thirty-three primary care
practices in Stockholm, Sweden. SUBJECTS: GPs and nurses working in primary care.
MAIN OUTCOME MEASURES: Thematic descriptions of academic detailing by
pharmacists. RESULTS: Five themes were identified: 1) Complexity in 3 'P':
patients, pharmacotherapy, and primary care; 2) What, when, who? Clash between
GPs' and nurses' experiences and guidelines; 3) Real-world problems and less-than
ideal solutions; 4) Eureka? Experiences with different steps during a medication
review; and 5) Threats to GP autonomy. CONCLUSION: GPs and nurses should
participate in the construction and release of guidelines in order to increase
their usability in clinical practice. Future research should analyse if
alternative strategies such as condensed medical reviews and feedback on
prescribing are easier to implement in primary care. Key points Complex
medication reviews have been introduced on a large scale in Swedish primary care,
but knowledge on GPs' and nurses' views on such reviews is lacking. In the
context of primary care alternative strategies such as condensed medication
reviews and feedback on prescribing may be more applicable than medication
reviews according to guidelines. GPs and nurses should make contributions to the
development of guidelines on medication reviews in order to increase their
usability in clinical practice.
PMID- 29956571
TI - Autophagic reliance promotes metabolic reprogramming in oncogenic KRAS-driven
tumorigenesis.
AB - Defects in basal autophagy limit the nutrient supply from recycling of
intracellular constituents. Despite our understanding of the prosurvival role of
macroautophagy/autophagy, how nutrient deprivation, caused by compromised
autophagy, affects oncogenic KRAS-driven tumor progression is poorly understood.
Here, we demonstrate that conditional impairment of the autophagy gene Atg5 (atg5
KO) extends the survival of KRASG12V-driven tumor-bearing mice by 38%. atg5-KO
tumors spread more slowly during late tumorigenesis, despite a faster onset. atg5
KO tumor cells displayed reduced mitochondrial function and increased
mitochondrial fragmentation. Metabolite profiles indicated a deficiency in the
nonessential amino acid asparagine despite a compensatory overexpression of ASNS
(asparagine synthetase), key enzyme for de novo asparagine synthesis. Inhibition
of either autophagy or ASNS reduced KRASG12V-driven tumor cell proliferation,
migration, and invasion, which was rescued by asparagine supplementation or
knockdown of MFF (mitochondrial fission factor). Finally, these observations were
reflected in human cancer-derived data, linking ASNS overexpression with poor
clinical outcome in multiple cancers. Together, our data document a widespread
yet specific asparagine homeostasis control by autophagy and ASNS, highlighting
the previously unrecognized role of autophagy in suppressing the metabolic
barriers of low asparagine and excessive mitochondrial fragmentation to permit
malignant KRAS-driven tumor progression.
PMID- 29956574
TI - The use of a gene expression signature and connectivity map to repurpose drugs
for bipolar disorder.
AB - OBJECTIVES: To create a gene expression signature (GES) to represent the
biological effects of a combination of known drugs for bipolar disorder (BD) on
cultured human neuronal cells (NT2-N) and rat brains, which also has evidence of
differential expression in individuals with BD. To use the GES to identify new
drugs for BD using Connectivity Map (CMap). METHODS: NT2-N (n = 20) cells and
rats (n = 8) were treated with a BD drug combination (lithium, valproate,
quetiapine and lamotrigine) or vehicle for 24 and 6 h, respectively. Following
next-generation sequencing, the differential expression of genes was assessed
using edgeR in R. The derived GES was compared to differentially expressed genes
in post-mortem brains of individuals with BD. The GES was then used in CMap
analysis to identify similarly acting drugs. RESULTS: A total of 88 genes showed
evidence of differential expression in response to the drug combination in both
models, and therefore comprised the GES. Six of these genes showed evidence of
differential expression in post-mortem brains of individuals with BD. CMap
analysis identified 10 compounds (camptothecin, chlorambucil, flupenthixol,
valdecoxib, rescinnamine, GW-8510, cinnarizine, lomustine, mifepristone and
nimesulide) acting similarly to the BD drug combination. CONCLUSIONS: This study
shows that GES and CMap can be used as tools to repurpose drugs for BD.
PMID- 29956573
TI - A pilot investigation into the effects of acute normobaric hypoxia, high altitude
exposure and exercise on serum angiotensin-converting enzyme, aldosterone and
cortisol.
AB - INTRODUCTION: Aldosterone decreases at high altitude (HA) but the effect of
hypoxia on angiotensin-converting enzyme (ACE), a key step in the renin
angiotensin-aldosterone system, is unclear. METHODS: We investigated the effects
of exercise and acute normobaric hypoxia (NH, ~11.0% FiO2) on nine participants
and six controls undertaking the same exercise at sea level (SL). NH exposure
lasted 5 hours with 90 minutes of submaximal treadmill walking. Blood samples for
aldosterone, ACE and cortisol were taken throughout exposure and at rest during a
trek to HA (5140 m) in eight separate participants. RESULTS: There was no
difference in cortisol or aldosterone between groups pre-exercise. Aldosterone
rose with exercise to a greater extent at SL than in NH (post-exercise: 700 +/-
325 versus 335 +/- 238 pmol/L, mean +/- SD, p = 0.044). Conversely, cortisol rose
to a greater extent in NH (post-exercise: 734 +/- 165 versus 344 +/- 159 nmol/L,
mean +/- SD, p = 0.001). There were no differences in ACE activity. During the
trek to HA, resting aldosterone and cortisol reduced with no change in ACE.
CONCLUSIONS: Acute NH subdues the exercise-associated rise in aldosteroe but
stimulates cortisol, whereas prolonged exposure at HA reduces both resting
aldosterone and cortisol. As ACE activity was unchanged in both environments,
this is not the mechanism underlying the fall in aldosterone.
PMID- 29956575
TI - Immunohistochemical analysis and comparison of napsin A, TTF1, SPA and CK7
expression in primary lung adenocarcinoma.
AB - We investigated the expression of napsin A, TTF1, SPA and CK7 in primary lung
adenocarcinoma (ADC) and compared antibody specificity and sensitivity. We used
immunohistochemistry (IHC) using antibodies directed against napsin A, TTF1, SPA,
and CK7 on cancer tissue from 454 patients diagnosed with lung cancer. In primary
lung ADC, napsin A exhibited a sensitivity of 87.25% and specificity of 95.02%,
TTF1 exhibited a sensitivity of 80.72% and specificity of 90.48%, SPA exhibited a
sensitivity of 60.46% and specificity of 94.87% and CK7 exhibited a sensitivity
of 100% and specificity of 80.31%. The order of sensitivity of the four
indicators was CK7 > napsin A > TTF1 > SPA, and the order of specificity was
napsin A > SPA > TTF1 > CK7. We can select effective indicators for diagnostic
and differential diagnostic purposes based on differences in sensitivity and
specificity.
PMID- 29956576
TI - Impact of cannabis legalization on treatment and research priorities for cannabis
use disorder.
AB - An increasing proportion of the world has legalized cannabis for medicinal or
recreational use. The legalization trend appears to be continuing. These changes
in the legislative landscape may have important health, treatment, and research
implications. This review discusses public health outcomes that may be impacted
by increases in cannabis availability and use. It additionally considers
potential research and treatment priorities in the face of widespread cannabis
legalization.
PMID- 29956577
TI - Levels and patterns of genetic variation in Japanese whiting (Sillago japonica)
based on mitochondrial DNA control region.
AB - Japanese whiting (Sillago japonica) is a commercially important demersal fish
distributed along the coasts of East Asia and becomes recently an aquaculture
species. Despite its commercial importance, the levels and patterns of population
genetic variation remain poorly understood. In this study, 346 specimens were
collected from 14 localities along the coastal waters of China, Korea and Japan
and their genetic variation was analyzed with mtDNA control region (D-loop)
sequences. A total of 131 polymorphic sites were detected which determined 294
haplotypes. A pattern with high levels of haplotype diversity (h = 0.999 +/-
0.001) and nucleotide diversity (l = 0.030 +/- 0.015) was detected in the
examined range. Analyses of analysis of molecular variance (AMOVA) and Fst showed
that no significant genetic differentiation existed among China, Korea and Japan
populations, excepting for the populations between Ise Bay (IBP) sample and the
other ones. Minimum spanning tree (MST), neutrality tests, mismatch distribution
and Bayesian skyline analyses indicated that the species along coastline of
China, Korea and Japan have experienced population expansions originated in its
most recent history at about 106-423 kya during the late Pleistocene glaciations
and deglaciations periods.
PMID- 29956578
TI - Renal Function Salvage After Delayed Endovascular Revascularization of Acute
Renal Artery Occlusion in Patients With Fenestrated-Branched Endovascular
Aneurysm Repair or Visceral Debranching.
AB - PURPOSE: To analyze the renal function and outcome after delayed (>6 hours)
endovascular revascularization of acute renal artery occlusion (RAO) in patients
with fenestrated-branched endovascular aneurysm repairs (EVARs) or open visceral
debranching. METHODS: A single-center retrospective analysis was conducted
involving 7 patients (mean age 61 years, range 49-72; 5 women) with 9 RAOs
treated with endovascular revascularization between December 2014 and March 2017.
Three patients had a solitary kidney with chronic renal insufficiency; 1 patient
had bilateral occlusions as the acute event. Initial aortic surgery included 5
branched and 1 fenestrated EVAR as well as 1 open visceral debranching operation.
Revascularization of the RAO was performed using aspiration thrombectomy, local
lysis therapy, and stent-graft relining. The median time between initial aortic
surgery and RAO was 10 months (range 0.5-17). RESULTS: Median renal ischemic time
to revascularization was 24 hours (range 7-168). Technical success was 100%, with
1 procedure-related access complication. Temporary dialysis dependency occurred
in 4 patients. Mean in-hospital stay was 17 days (range 7-32) with 1
postoperative death at day 10 due to cardiac arrest of unknown cause. Mean follow
up was 10.3 months (range 1.5-27) in 5 of 6 discharged patients. During follow
up, 1 reintervention for recurrent occlusion was performed. At follow-up imaging,
all renal arteries were patent. No permanent dialysis dependency occurred.
CONCLUSION: Renal function can be salvaged by delayed revascularization for RAO
with prolonged renal ischemia. The endovascular approach with aspiration
thrombectomy, local lysis, and stent-graft relining is a feasible technique for
revascularization after RAO in patients with fenestrated-branched EVAR or open
visceral debranching.
PMID- 29956579
TI - 3D MicroCT spatial and temporal characterization of thoracic aorta perivascular
adipose tissue and plaque volumes in the ApoE-/- mouse model.
AB - Perivascular adipose tissue (PVAT) influences vascular function and pathology. We
present a protocol using micro-computed tomography (microCT), a novel imaging
technique typically used for hard biological tissue, to characterize the temporal
and spatial development of aorta PVAT and luminal plaque soft tissue.
Apolipoprotein E deficient (ApoE) and C57Bl/6J (control) mice were fed a high fat
western diet up to 30 weeks. 3D microCT reconstructions were used to quantify: 1)
vascular wall volume, a surrogate measure of remodeling, was greater in ApoE, 2)
aorta PVAT volume was reduced in ApoE, 3) plaque volumes increased over time in
ApoE, 4) plaque development co-localized with luminal ostia, origins of branching
arteries, which traveled through areas of greatest PVAT volume, 5) qualitatively,
the same arteries showed evidence of increased tortuosity in ApoE. This study
reflects the potential of microCT analyses to assess vascular wall, PVAT and
arterial trajectory modifications in relevant animal models. Abbreviations: PVAT:
perivascular adipose tissue; ApoE: apolipoprotein E deficient mouse strain;
Control: C57Bl/6J mouse strain; PTA: 0.3% phosphotungstic acid; microCT: micro
computed tomography; CV: cardiovascular; CVD: cardiovascular disease; IQR:
interquartile range; PPARgamma: peroxisome proliferator activated receptor -
gamma; VV: vasa vasorum; 3D: three dimensional.
PMID- 29956580
TI - Treating pancreatic cancer: more antioxidants more problems?
PMID- 29956581
TI - Nurse Practitioners as Disruptive Innovators in Palliative Medicine.
AB - As the population ages, the corresponding rise in people living with life
limiting illnesses will lead to a greater need for clinician experts in
palliative medicine. There are not enough physicians available to care for the
growing number of patients, however. We believe that nurse practitioners are well
positioned to meet this demand. In this paper, we will use the concept of
disruptive innovations to provide support for our belief that nurse practitioners
can, and should, take a larger role in palliative medicine. First, we will
describe how 2 general types of business models-solution shops and value-adding
processes-can be applied to health care in general and palliative medicine
specifically. Second, we will describe the concept of disruptive innovations.
Finally, we will use these business models to explain how nurse practitioners are
particularly well suited to disrupt the current business model of palliative
medicine, thereby allowing more patients with life-limiting illness to receive
the high-quality care they need.
PMID- 29956582
TI - Chronic inflammatory pain induced GABAergic synaptic plasticity in the adult
mouse anterior cingulate cortex.
AB - Background Chronic pain is a persistent unpleasant sensation that produces
pathological synaptic plasticity in the central nervous system. Both human
imaging study and animal studies consistently demonstrate that the anterior
cingulate cortex is a critical cortical area for nociceptive and chronic pain
processing. Thus far, the mechanisms of excitatory synaptic transmission and
plasticity have been well characterized in the anterior cingulate cortex for
various models of chronic pain. By contrast, the potential contribution of
inhibitory synaptic transmission in the anterior cingulate cortex, in models of
chronic pain, is not fully understood. Methods Chronic inflammation was induced
by complete Freund adjuvant into the adult mice left hindpaw. We performed in
vitro whole-cell patch-clamp recordings from layer II/III pyramidal neurons in
two to three days after the complete Freund adjuvant injection and examined if
the model could cause plastic changes, including transient and tonic type A gamma
aminobutyric acid (GABAA) receptor-mediated inhibitory synaptic transmission, in
the anterior cingulate cortex. We analyzed miniature/spontaneous inhibitory
postsynaptic currents, GABAA receptor-mediated tonic currents, and evoked
inhibitory postsynaptic currents. Finally, we studied if GABAergic transmission
related proteins in the presynapse and postsynapse of the anterior cingulate
cortex were altered. Results The complete Freund adjuvant model reduced the
frequency of both miniature and spontaneous inhibitory postsynaptic currents
compared with control group. By contrast, the average amplitude of these currents
was not changed between two groups. Additionally, the complete Freund adjuvant
model did not change GABAA receptor-mediated tonic currents nor the set of evoked
inhibitory postsynaptic currents when compared with control group. Importantly,
protein expression of vesicular GABA transporter was reduced within the
presynpase of the anterior cingulate cortex in complete Freund adjuvant model. In
contrast, the complete Freund adjuvant model did not change the protein levels of
GABAA receptors subunits such as alpha1, alpha5, beta2, gamma2, and delta.
Conclusion Our results suggest that the induction phase of inflammatory pain
involves spontaneous GABAergic plasticity at presynaptic terminals of the
anterior cingulate cortex.
PMID- 29956584
TI - Examining the effectiveness of the Cultural Formulation Interview with young
children: A clinical illustration.
AB - After years of extensive research, the Cultural Formulation Interview (CFI) was
released in the fifth edition of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-5). Similar to its predecessor, the Outline of the Cultural
Formulation (OCF), the CFI aims to refine the psychiatric assessment process by
systematically examining cultural factors. However, in contrast to the OCF which
employs open-ended questions, the CFI uses a semi-structured interview format.
Unfortunately, children and adolescents have only been included in a handful of
OCF and CFI studies, which raises questions about their applicability with youth,
particularly young children (11 years or younger). In this article, we start
examining the usefulness of the CFI with young children and propose
recommendations to enhance its benefits by suggesting the development of a
supplementary module specifically designed for young children. These ideas are
illustrated with the assessment of a 6-year-old boy of Somali descent.
PMID- 29956583
TI - Inhibition of renin-angiotensin axis reduces the risk of thrombus formation in
the left atrial appendage in patients with hypertension complicated by atrial
fibrillation.
AB - AIMS: We examined whether the use of a renin-angiotensin-aldosterone system (RAS)
inhibitor plays a role in protecting against left atrial appendage thrombus
(LAAT) in patients with hypertension complicated by atrial fibrillation (AF).
METHODS: Two observational studies were conducted on patients with diagnoses of
hypertension and AF, who were categorized into RAS inhibitor user or nonuser
groups. Demographic characteristics, clinical characteristics, echocardiographic
parameters and hemostatic markers were examined and the occurrence of LAAT during
follow-up were recorded. RESULTS: In the first study ( n = 131), LA peak systolic
strain and LAA emptying flow velocity (LAA eV) were significantly increased in
patients on RAS inhibitors compared with the nonuser group ( p < 0.05). Lower D
dimer and fibrinogen levels were observed in patients on RAS inhibitors ( p <
0.05). In the second study ( n = 99), 25.9% ( n = 11) of patients on RAS
inhibitors developed LAAT, compared with 46.7% ( n = 21) in the nonuser group ( p
< 0.05). After controlling for risk factors related to LAAT, use of RAS
inhibitors remained associated with a significantly lower risk of developing LAAT
(HR, 0.406; 95% CI, 0.191-0.862; p = 0.019). CONCLUSIONS: RAS inhibitors use was
associated with a significant reduction in the risk of LAAT in patients with
hypertension and AF.
PMID- 29956585
TI - Nuclear factor kappa B regulated monocyte chemoattractant protein-1/chemokine CC
motif receptor-2 expressing in spinal cord contributes to the maintenance of
cancer-induced bone pain in rats.
AB - BACKGROUND: Chemokine, monocyte chemoattractant protein-1 (MCP-1), is a potential
factor to cause cancer-induced bone pain (CIBP). NF-kappaB signaling is very
important in mediating the expression of chemokines and may have a role in CIBP.
However, the mechanism is still unclear. This study investigates the role of NF
kappaB in CIBP by regulating MCP-1/chemokine CC motif receptor-2 (CCR2) signaling
pathway. METHODS: A rat CIBP model was established by injecting Walker-256 cells
into the tibia medullary cavity. Nine days later, animals were intrathecally
administrated with MCP-1 neutralizing antibody, CCR2 antagonist (RS504393), or NF
kB inhibitor (BAY11-7081). Mechanical paw withdrawal threshold was used to assess
pain behavior and sciatic functional index, and radiographic images were adopted
to evaluate the damage of nerve and bone. The spinal cords were harvested for
Western blot and quantitative reverse transcription polymerase chain reaction.
The distribution of MCP-1, CCR2, and NF-kB was detected by double
immunofluorescent staining. RESULTS: CIBP caused remarkable bone destruction,
injury of sciatic and femoral nerve, and persistent (>15 days) mechanical
allodynia in rats. Tumor cell inoculation upregulate MCP-1 and NF-kB in activated
neurons as well as CCR2 in neurons and microglia of the spinal cord. MCP-1
antibody, RS504393, and BAY11-7081 partially reversed CIBP-induced mechanical
allodynia, and CIBP regulated the expression levels of pro-inflammatory
cytokines, tumor necrosis factor-alpha and interferon-gamma, and anti
inflammatory cytokine, interleukin 4, and BAY11-7081 lowered CIBP-induced MCP-1
and CCR2 expressions in a dose-dependent manner. CONCLUSION: In conclusion, NF-kB
signaling pathway regulates the expressions of MCP-1/CCR2-induced inflammatory
factors in the spinal cord of CIBP rats.
PMID- 29956586
TI - Nonmuscle myosin II isoforms interact with sodium channel alpha subunits.
AB - Sodium channels play pivotal roles in health and diseases due to their ability to
control cellular excitability. The pore-forming alpha-subunits (sodium channel
alpha subunits) of the voltage-sensitive channels (i.e., Nav1.1-1.9) and the
nonvoltage-dependent channel (i.e., Nax) share a common structural motif and
selectivity for sodium ions. We hypothesized that the actin-based nonmuscle
myosin II motor proteins, nonmuscle myosin heavy chain-IIA/myh9, and nonmuscle
myosin heavy chain-IIB/myh10 might interact with sodium channel alpha subunits to
play an important role in their transport, trafficking, and/or function.
Immunochemical and electrophysiological assays were conducted using rodent
nervous (brain and dorsal root ganglia) tissues and ND7/23 cells coexpressing Nav
subunits and recombinant myosins. Immunoprecipitation of myh9 and myh10 from
rodent brain tissues led to the coimmunoprecipitation of Nax, Nav1.2, and Nav1.3
subunits, but not Nav1.1 and Nav1.6 subunits, expressed there. Similarly,
immunoprecipitation of myh9 and myh10 from rodent dorsal root ganglia tissues led
to the coimmunoprecipitation of Nav1.7 and Nav1.8 subunits, but not Nav1.9
subunits, expressed there. The functional implication of one of these
interactions was assessed by coexpressing myh10 along with Nav1.8 subunits in
ND7/23 cells. Myh10 overexpression led to three-fold increase ( P < 0.01) in the
current density of Nav1.8 channels expressed in ND7/23 cells. Myh10 coexpression
also hyperpolarized voltage-dependent activation and steady-state fast
inactivation of Nav1.8 channels. In addition, coexpression of myh10 reduced ( P <
0.01) the offset of fast inactivation and the amplitude of the ramp currents of
Nav1.8 channels. These results indicate that nonmuscle myosin heavy chain-IIs
interact with sodium channel alpha subunits subunits in an isoform-dependent
manner and influence their functional properties.
PMID- 29956587
TI - Therapeutic potential of Pak1 inhibition for pain associated with cutaneous burn
injury.
AB - Painful burn injuries are among the most debilitating form of trauma, globally
ranking in the top 15 leading causes of chronic disease burden. Despite its
prevalence, however, chronic pain after burn injury is under-studied. We
previously demonstrated the contribution of the Rac1-signaling pathway in several
models of neuropathic pain, including burn injury. However, Rac1 belongs to a
class of GTPases with low therapeutic utility due to their complex intracellular
dynamics. To further understand the mechanistic underpinnings of burn-induced
neuropathic pain, we performed a longitudinal study to address the hypothesis
that inhibition of the downstream effector of Rac1, Pak1, will improve pain
outcome following a second-degree burn injury. Substantial evidence has
identified Pak1 as promising a clinical target in cognitive dysfunction and is
required for dendritic spine dysgenesis associated with many neurological
diseases. In our burn injury model, mice exhibited significant tactile allodynia
and heat hyperalgesia and dendritic spine dysgenesis in the dorsal horn. Activity
dependent expression of c-fos also increased in dorsal horn neurons, an indicator
of elevated central nociceptive activity. To inhibit Pak1, we repurposed an FDA
approved inhibitor, romidepsin. Treatment with romidepsin decreased dendritic
spine dysgenesis, reduced c-fos expression, and rescued pain thresholds. Drug
discontinuation resulted in a relapse of cellular correlates of pain and in lower
pain thresholds in behavioral tests. Taken together, our findings identify Pak1
signaling as a potential molecular target for therapeutic intervention in
traumatic burn-induced neuropathic pain.
PMID- 29956588
TI - MiR-125b blocks Bax/Cytochrome C/Caspase-3 apoptotic signaling pathway in rat
models of cerebral ischemia-reperfusion injury by targeting p53.
AB - OBJECTIVE: To explore the potential effect of miR-125b on p53-mediated
regulation of Bax/Cytochrome C/Caspase-3 apoptotic signaling pathway in rats with
cerebral ischemia-reperfusion (CIR) injury. METHODS: Sprague-Dawley (SD) rats
were used to conduct CIR injury and injected with miR-125b mimic/inhibitor or p53
inhibitor (Pifithrin-alpha, PFT-alpha). Dual-luciferase reporter gene assay was
used to analyze the targeting relationship between miR-125b and p53. Longa
scoring and Triphenyl tetrazolinm chloride (TTC) staining were used to test the
neurologic function and determine infarct size, respectively. Hematoxylin-eosin
(HE) and Nissl's stainings were conducted to observe the morphology of cortical
neurons. Neuronal nuclei (NeuN) expression was detected by immunohistochemical
staining. QRT-PCR was performed to detect the expressions of miR-125b and p53.
TUNEL staining and Western blotting was used to determine neuronal apoptosis and
expressions of Bax/Cytochrome C/Caspase-3 signaling pathway-related proteins,
respectively. RESULTS: Our results showed that miR-125b could directly target
p53. As observed, overexpression of miR-125b could obviously reduce the
neurological score, infarct size, and brain water content after CIR in rats,
which also improved the morphology of cortical neurons, increased the number of
neurons, reduced neuronal apoptosis, and inhibited the expressions of
Bax/Cytochrome C/Caspase-3 pathway. Moreover,the similar results were observed in
rats with CIR after injected with PFT-alpha. But no significant differences in
each index were found in CIR group and CIR + anti-miR-125b + PFT-alpha group.
CONCLUSION: MiR-125b exerts protective effects on CIR injury through inhibition
of Bax/Cytochrome C/Caspase-3signaling pathway via targeting p53, which is likely
to be a promising treatment for CIR. ABBREVIATIONS: 3'-UTR: 3-untranslated
region; CIR: cerebral ischemia-reperfusion; CIS: cerebral ischemic stroke; PFT
alpha: Pifithrin-alpha; PVDF: polyvinylidene fluoride; SD: Sprague-Dawley; TBST:
tris buffered saline with tween. TTC staining: Triphenyl tetrazolinm chloride
staining; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick
end labeling.
PMID- 29956589
TI - Coherent Coding of Enhanced Interaural Cues Improves Sound Localization in Noise
With Bilateral Cochlear Implants.
AB - Bilateral cochlear implant (BCI) users only have very limited spatial hearing
abilities. Speech coding strategies transmit interaural level differences (ILDs)
but in a distorted manner. Interaural time difference (ITD) information
transmission is even more limited. With these cues, most BCI users can coarsely
localize a single source in quiet, but performance quickly declines in the
presence of other sound. This proof-of-concept study presents a novel signal
processing algorithm specific for BCIs, with the aim to improve sound
localization in noise. The core part of the BCI algorithm duplicates a monophonic
electrode pulse pattern and applies quasistationary natural or artificial ITDs or
ILDs based on the estimated direction of the dominant source. Three experiments
were conducted to evaluate different algorithm variants: Experiment 1 tested if
ITD transmission alone enables BCI subjects to lateralize speech. Results showed
that six out of nine BCI subjects were able to lateralize intelligible speech in
quiet solely based on ITDs. Experiments 2 and 3 assessed azimuthal angle
discrimination in noise with natural or modified ILDs and ITDs. Angle
discrimination for frontal locations was possible with all variants, including
the pure ITD case, but for lateral reference angles, it was only possible with a
linearized ILD mapping. Speech intelligibility in noise, limitations, and
challenges of this interaural cue transmission approach are discussed alongside
suggestions for modifying and further improving the BCI algorithm.
PMID- 29956590
TI - Do Hearing Aids Address Real-World Hearing Difficulties for Adults With Mild
Hearing Impairment? Results From a Pilot Study Using Ecological Momentary
Assessment.
AB - Current approaches to the measurement of hearing aid benefit typically use
clinical or laboratory-based speech perception tests or retrospective self-report
surveys. However, when assessing hearing aid outcomes in adults with mild hearing
impairment, the traditional outcome measures may not be sufficiently sensitive.
An alternative to these techniques are approaches that capture data about real
world experiences as they are experienced, such as ecological momentary
assessment. This single-subject experimental design pilot study investigated the
feasibility of using ecological momentary assessment in assessing whether hearing
aids make a difference to the real-world listening experiences of adults with
mild hearing impairment. Ten participants with an average age of 70 years and no
previous amplification experience answered survey questions on their listening
experiences over a 4-week period (1 week without hearing aids, 2 weeks with
hearing aids, and 1 week without hearing aids). A total of 860 surveys were
collected. Participants reported significantly better speech understanding and
less listening effort during the 2-week trial with hearing aids compared to
baseline conditions. In addition, they reported that they were significantly less
hampered by their hearing difficulties and had greater enjoyment of listening
events with wearing hearing aids. Individual variation in hearing aid benefit was
evident. This pilot study showed that ecological momentary assessment has
potential to quantify self-reported aided benefit for individuals with mild
hearing impairment fitted with hearing aids. This research also highlighted that
a real-world approach is needed to explore individualized outcomes and provide
different insights to standardized questionnaires.
PMID- 29956591
TI - Efficacy of a Hearing Aid Noise Reduction Function.
AB - Noise reduction systems have been implemented in hearing aids to improve signal
to-noise ratio and listening comfort. The aim of this study was to evaluate the
efficacy of hearing aid noise reduction for Mandarin speakers. The results showed
a significant improvement in acceptable noise levels and speech reception
thresholds with noise reduction turned on. Sound quality ratings also suggested
that most listeners preferred having noise reduction turned on for listening
effort, listening comfort, speech clarity, and overall sound quality. These
results suggest that the noise reduction system used in this study might improve
sentence perception in steady-state noise, noise tolerance, and sound quality,
although not all listeners preferred aggressive noise reduction. However, due to
large interindividual variation, clinical application of the results should be on
an individual basis.
PMID- 29956592
TI - Infarct location is associated with quality of life after mild ischemic stroke.
AB - Background In patients with mild ischemic stroke, small but eloquent infarcts may
have devastating effects, particularly on health-related quality of life. Aim
This study investigates the association between acute infarct location and three
month health-related quality of life in patients with mild ischemic stroke.
Methods We evaluated consecutively enrolled patients from a single center between
August 2012 and July 2013. Our primary outcome at three months was impairment in
any health-related quality of life domain (upper extremity, lower extremity,
executive function, and general concerns) defined by a T-score <45. We analyzed
the association between acute infarct locations and impaired health-related
quality of life at three months in univariate and multivariable analysis. Results
Among 229 patients (mean age 64.9 years, 55% male, 29.7% black, and median
initial NIHSS score 1), impaired health-related quality of life was noted in 84
(36.2%) patients at three months. In univariate analysis, patients with
subcortical infarcts (56.0% vs. 39.3%, p = 0.02) and brainstem infarcts (21.4%
vs. 10.3%, p = 0.02) were more likely to have impaired health-related quality of
life. In multivariable analysis, patients with subcortical and/or brainstem
infarcts had increased odds of impaired health-related quality of life (adjusted
OR 2.54, 95% CI 1.29-5.01, p = 0.01). Conclusions After mild ischemic stroke,
subcortical and brainstem infarct locations predict impairment in health-related
quality of life.
PMID- 29956593
TI - Sexual health interventions for young people in state care: a systematic review.
AB - OBJECTIVES: To describe evaluated sexual health interventions for young people in
state care and provide an assessment of the quality of and evidence for these
interventions. METHODS: A systematic review of sexual health interventions for
young people in state care was conducted. Randomised controlled trials and quasi
experimental designs were eligible, 2051 records were screened, 412 full-text
studies retrieved, and 12 publications with low-to-moderate risk of bias
included. RESULTS: Due to substantial heterogeneity in study populations,
settings, intervention approaches, outcomes and measures, standard summary
measures for intervention outcomes was not used. Instead, data were synthesised
across studies and presented narratively. CONCLUSION: Without making
recommendations, the result suggests that group-based educational interventions
in general increase knowledge, attitudes and behaviour compared with standard
care. However, these findings need to be further investigated, with a special
emphasis on cultural context and the involvement of young people.
PMID- 29956594
TI - Influence of improvement or worsening of glucose tolerance on risk of stroke in
persons with impaired glucose tolerance.
AB - BACKGROUND AND AIM: We sought to determine the effect of regression to normal
glucose tolerance (NGT) or progression to diabetes in early years of impaired
glucose tolerance (IGT) on subsequent risk of stroke. METHODS: In 1986, 576
adults aged 25 years and older with impaired glucose tolerance in Da Qing, China,
were randomly assigned by clinic to control, diet, exercise, or diet plus
exercise intervention groups for a six-year period. Subsequently participants
received medical care in their local clinics. We tracked participants for
additional 17 years to ascertain stroke events and other outcomes. RESULTS: At
the end of 6-year intervention trial follow-up, 272 (50.2%) had progressed to
diabetes, 169 (31.2%) regressed to normal glucose tolerance, and 101 (18.6%)
remained impaired glucose tolerance. During the subsequent 17-year follow-up, 173
(31.9%) developed a stroke, 26.7% of normal glucose tolerances, 30.7% of impaired
glucose tolerances, and 36.1% of those with diabetes. After controlling for age,
sex, baseline blood pressure, smoking, total cholesterol, previous cardiovascular
disease and intervention group, those who developed diabetes in the first six
years had a higher incidence of stroke than those who reverted to normal glucose
tolerance (HR = 1.49, 95% CI 1.01-2.19, p = 0.04), whereas for those who remained
impaired glucose tolerance compared to those who regressed to normal glucose
tolerance the HR was 1.25 (95% CI 0.80-1.93; p = 0.30). A 1-mmol/L increase in
both fasting and 2-h post-load plasma glucose from entry to end of the six-year
trial was significantly associated with a higher risk of development of stroke in
the subsequent 17 years, respectively (HR = 1.07, 95% CI 1.03-1.11, p < 0.0001
for fasting glucose, HR = 1.05, 95% CI 1.02-1.09, p = 0.007 for 2-h post-load
plasma glucose). CONCLUSIONS: Among Chinese adults with impaired glucose
tolerance, early progression to diabetes predicted a higher risk of stroke,
compared those who regressed to normal glucose tolerance.
PMID- 29956595
TI - Ethnic inequalities in child and adolescent health in the Scandinavian welfare
states: The role of parental socioeconomic status - a systematic review.
AB - AIMS: Adult non-Western immigrants in Scandinavia tend to be worse off in terms
of health than native-born populations, which cannot be fully ascribed to their
often lower socioeconomic status (SES). This review examines if differences in
health status are also present between non-Western immigrant and majority
children in Denmark, Norway and Sweden, and if SES explains the differences.
METHODS: Following PRISMA guidelines, relevant Scandinavian peer-reviewed
quantitative publications since 1990 were identified through a systematic search
of PubMed, EMBASE, Scopus, Web of Science and SveMed. Of 1197 identified
publications, 27 remained relevant after applying inclusion criteria: 3 Danish, 6
Norwegian and 18 Swedish studies. RESULTS: Non-western immigrant children had
overall poorer outcomes compared with ethnic majority children in Denmark, Norway
and Sweden in health issues covered by the included studies: diabetes, obesity,
oral and mental health, and well-being. However, in diabetes, obesity and mental
health, non-Western immigrant children from certain countries and regions, and
descendants of non-Western immigrants had similar/more favourable outcomes than
majority children. In mental health and well-being, ethnic inequalities were
strongly associated with SES, while for diabetes, obesity and oral health,
differences remained significant after adjusting for SES. CONCLUSIONS: Overall
poorer health outcomes in non-Western immigrant compared with majority children
in Scandinavia cannot be fully explained by SES. Evidence points to additional
mechanisms at individual, household, societal or policy levels, including reasons
for migration, culture and societal discrimination. Finally, methodological
issues may influence study outcomes, e.g. heterogeneity of populations studied
and socioeconomic variables included.
PMID- 29956596
TI - Responding to Richard: Celebrity and (mis)representation of science.
AB - Drawing on 48 in-depth interviews conducted with biologists and physicists at
universities in the United Kingdom, this study examines scientists' perceptions
of the role celebrity scientists play in socially contentious public debates. We
examine Richard Dawkins' involvement in public debates related to the
relationship between science and religion as a case to analyze scientists'
perceptions of the role celebrity scientists play in the public sphere and the
implications of celebrity science for the practice of science communication.
Findings show that Dawkins' proponents view the celebrity scientist as a
provocateur who asserts the cultural authority of science in the public sphere.
Critics, who include both religious and nonreligious scientists, argue that
Dawkins misrepresents science and scientists and reject his approach to public
engagement. Scientists emphasize promotion of science over the scientist,
diplomacy over derision, and dialogue over ideological extremism.
PMID- 29956597
TI - Children with post-stroke epilepsy have poorer outcomes one year after stroke.
AB - Background Epilepsy is a common complication of pediatric stroke. Aim In this
study, we aim to measure the association between epilepsy and neurologic outcome
after childhood arterial ischemic stroke. Methods Prospective cohort study of
children (29 days-19 years) enrolled after an acute arterial ischemic stroke at
21 international pediatric stroke centers and followed to identify epilepsy. One
year post-stroke, outcomes were scored using the examination-based Pediatric
Stroke Outcome Measure (range = 0-10); higher values reflect greater disability.
Ordinal logistic regression was used to measure the association of Pediatric
Stroke Outcome Measure scores (categorized as 0-1, 1.5-3, 3.5-6, 6.5-10) with
epilepsy. Results Investigators enrolled 86 children (median age = 6.1 years,
interquartile range (IQR) = 1.4-12.2 years) with acute stroke. At 1 year, 18/80
(23%) remained on an anticonvulsant including 8/80 (10%) with epilepsy. Among the
70 with Pediatric Stroke Outcome Measure scored, the median was 0.5 (IQR = 0-1.5)
for children without epilepsy ( n = 63), and 6 (IQR = 0.5-10) for children with
epilepsy ( n = 7). In univariable analyses, poorer 1-year outcome was associated
with middle cerebral artery stroke, cortical infarcts, hemorrhagic
transformation, hospital disposition not to home, and epilepsy. In multivariable
analysis, middle cerebral artery stroke (odds ratio (OR) = 4.9, 95% confidence
intervals (CI) = 1.1-21.3) and epilepsy (OR = 24.1, CI = 1.5-380) remained
associated with poorer outcome. Conclusions Children who developed epilepsy
during the first year post-stroke had poorer neurologic outcomes than those
without epilepsy.
PMID- 29956598
TI - Baseline NIH Stroke Scale is an inferior predictor of functional outcome in the
era of acute stroke intervention.
AB - Background and aims Baseline National Institutes of Health Stroke Scale (NIHSS)
scores have frequently been used for prognostication after ischemic stroke. With
the increasing utilization of acute stroke interventions, we aimed to determine
whether baseline NIHSS scores are still able to reliably predict post-stroke
functional outcome. Methods We retrospectively analyzed prospectively collected
data from a high-volume tertiary-care center. We tested strength of association
between NIHSS scores at baseline and 24 h with discharge NIHSS using Spearman
correlation, and diagnostic accuracy of NIHSS scores in predicting favorable
outcome at three months (defined as modified Rankin Scale 0-2) using receiver
operating characteristic curve analysis with area under the curve. Results There
were 1183 patients in our cohort, with median baseline NIHSS 8 (IQR 3-17), 24-h
NIHSS 4 (IQR 1-11), and discharge NIHSS 2 (IQR 1-8). Correlation with discharge
NIHSS was r = 0.60 for baseline NIHSS and r = 0.88 for 24-h NIHSS. Of all
patients with follow-up data, 425/1037 (41%) had favorable functional outcome at
three months. Receiver operating characteristic curve analysis for predicting
favorable outcome showed area under the curve 0.698 (95% CI 0.664-0.732) for
baseline NIHSS, 0.800 (95% CI 0.772-0.827) for 24-h NIHSS, and 0.819 (95% CI
0.793-0.845) for discharge NIHSS; 24 h and discharge NIHSS maintained robust
predictive accuracy for patients receiving mechanical thrombectomy (AUC 0.846,
95% CI 0.798-0.895; AUC 0.873, 95% CI 0.832-0.914, respectively), while accuracy
for baseline NIHSS decreased (AUC 0.635, 95% CI 0.566-0.704). Conclusion Baseline
NIHSS scores are inferior to 24 h and discharge scores in predicting post-stroke
functional outcomes, especially in patients receiving mechanical thrombectomy.
PMID- 29956599
TI - To RAPIDly DEFUSE the stroke at DAWN: What is the key imaging?
PMID- 29956602
TI - Abstracts for Research and Audit Presentations.
PMID- 29956601
TI - The Royal Medico-Chirurgical Society of Glasgow (RMCSG) abstracts.
PMID- 29956604
TI - Editorial: The Real Impact of Target Therapy in Cancer Patients: Between Hope and
Reality.
PMID- 29956605
TI - Subtle Changes Due to Mutations in the GGDEF Domain Result in Loss of Biofilm
Forming Activity in the VC0395_0300 Protein from Vibrio cholerae, but No Major
Change in the Overall Structure.
AB - BACKGROUND: Cyclic-di-GMP (c-di-GMP) is a ubiquitous secondary messenger molecule
in bacteria synthesized by diguanylate cyclases. This universal messenger
regulates diverse cellular functions in bacteria at the transcriptional,
translational and posttranslational levels. The cellular functions regulated by c
di-GMP include cell motility, cell cycle progression, virulence, biofilm
formation, antibiotic production and other unknown functions. The VC0395_0300
protein from the chromosome I of the Vibrio cholerae classical strain O395,
serotype O1 has been established to be a diguanylate cyclase with a necessary
role in biofilm formation. OBJECTIVE: Mutations in the central position of the
GGEEF active site of VC0395_0300 protein have been created by site-directed
mutagenesis. The conditions for maximum production of mutated protein have been
optimized. While there is a significant loss-of-biofilm-forming activity in the
mutants, the basis for the same needed an investigation at the structural level.
METHODS: Subsequently, the mutant proteins have been characterized using
spectrofluorimetry and circular dichroism spectroscopy. RESULTS: While the
unfolding pattern of the mutant proteins shows some changes with respect to the
wild type, the overall structure of the protein does not show significant changes
due to the mutagenesis, despite the absence of biofilm formation in the mutants.
CONCLUSION: This led us to conclude that whatever changes that occur in the
mutated proteins, do not disturb the GGEEF domain architecture, but are
restricted to the local architecture, and are hence, subtle in nature.
PMID- 29956606
TI - Potential Uses of Venom Proteins in Treatment of HIV.
AB - BACKGROUND: For about 30 years Human Immunodeficiency Virus (HIV) has been a
significant social and health issue. It has been a perilous opponent in the human
contest against HIV. At the end of 2015 there were 26.7 million people worldwide
who were affected by the Human Immunodeficiency Virus (HIV) and this number is
expected to increase. Unfortunately, currently there are no vaccines available
for prevention and control of HIV. The global burden of HIV articulates the need
for anti-HIV therapeutic factors. Venom toxins are commonly prescribed for
treatment of various medical disorders. Honey Bee venom has recently been proven
to be safe and maybe therapeutic in a specified dose. This therapeutic effect is
due to the uptake of melittin by HIV infected cells which leads to decreased HIV
gene expression and replication. Similarly, Scorpion venom acts as a therapeutic
agent against HIV. Snake venoms have antiviral activity against defense
mechanisms of viruses. CONCLUSION: Antiretroviral therapy is promising in the
fight against HIV because it limits viral replication. It has the potential to
reduce the passage of HIV-1 and to limit the viral load in infected people. This
review aims to shed light on an infectious potential of active constituents of
bee, scorpion and snake venom articulated in many recent studies.
PMID- 29956607
TI - Phosphodiesterases (PDEs) from Snake Venoms: Therapeutic Applications.
AB - BACKGROUND: Snake venom, a highly poisonous and active venomous snake's
secretion, is a complex mixture of inorganic cations, carbohydrates, lipids,
proteins, peptides, toxins and hydrolytic enzymes of importance including
Phosphodiesterases (PDEs). These snake venom hydrolytic enzymes interfere in
different physiological processes. Snake venom PDEs have several roles to
metabolize extracellular nucleotides and to regulate nucleotide based
intercellular signalling mechanisms including platelet aggregation, which can
lead to death and debilitation in cardiac arrest and strokes in patients having
cerebro-vascular and cardiovascular diseases, hypertension and atherosclerosis
which is the primary cause of life-threatening diseases such as, stroke and
myocardial- infarction. CONCLUSION: PDEs are used to synthesize modified
oligonucleotides, which are useful in potential therapeutic applications.
Characterization of PDEs from different snake venoms has potential in identifying
new anticoagulants that target specific active sites, which leads to the
treatment of haemostatic disorders. Here, we review the snake venom PDEs
potential therapeutic activity against platelet aggregation which could provide
ideal platforms to design drugs for treatment or to fight against unwanted clots
formation.
PMID- 29956608
TI - Hyaluronidases: A Therapeutic Enzyme.
AB - BACKGROUND: Hyaluronidase is the most important enzyme found in the interstitial
matrix, effectively degrading the hyaluronic acid. Hyaluronidases are extensively
found in the venom of various animals such as snake, scorpion, spider and others.
Up till now five venom hyaluronidases are identified with a defined three
dimensional structure. These enzymes are involved in different biochemical,
physiological and pathological conditions like degradation of hyaluronic acid,
embryogenesis, transmembrane diffusion of drugs and toxins, inflammatory and
allergic response to antigens, healing of wounds, bacterial meningitis,
bacteremia and pneumonia. These enzymes are used as an adjuvant therapy in cancer
and to expedite the dispersion and absorption of drugs as well as to reduce the
tissue edema. and to reduce the progression of metastatic breast cancer as well
as used in ophthalmological procedures in combination with local anesthetics,
reduction of dermatological aging, regulation of hyaluronan, as a spreading
factor and with numerous clinical applications. CONCLUSION: In this review an
attempt was made to summarize the physiological, adjuvaent and therapeutic
significance of hyaluronidase enzymes from different animal sources.
PMID- 29956609
TI - Could flavonoids compete with synthetic azoles in diminishing Candida albicans
infections?
AB - Flavonoids are polyphenolic compounds with already confirmed various health
benefits. This review will shed light on flavonoids as potential antifungals in
Candida albicans infections. C. albicans is opportunistic pathogen able to cause
serious health issues due to numerous virulence factors amplifying its
pathogenicity. One of the most important virulence factors is Candida ability to
form biofilms which are highly resistant to treatment with antifungal drugs;
making diminishing of this pathogen even more challenging. This review will focus
on current knowledge on individual flavonoid compounds potential to deal with C.
albicans, with special turn on antibiofilm potential and insight into the mode of
action. Majority of the commercial drugs for treatment of candidiasis belong to
azole class, so the activity of flavonoids will be compared with the activity of
newly synthetized azole compounds, as well as with azole drugs that are already
on the market. This literature review will provide pros and cons for pushing
future research towards exploring novel synthetic azoles or further examination
of wide pallet of natural flavonoids.
PMID- 29956610
TI - Impact of natural dietary agents on multiple myeloma prevention and treatment:
molecular insights and potential for clinical translation.
AB - Chemoprevention is based on the use of non-toxic, pharmacologically active agents
to prevent tumor progression. In this regard, natural dietary agents have been
described by the most recent literature as promising tools for controlling onset
and progression of malignancies. Extensive research has been so far performed to
shed light on the effects of natural products on tumor growth and survival,
disclosing the most relevant signal transduction pathways targeted by such
compounds. Overall, anti-inflammatory, anti-oxidant and cytotoxic effects of
dietary agents on tumor cells are supported either by results from
epidemiological or animal studies, and even by clinical trials. Multiple myeloma
is a hematologic malignancy characterized by abnormal proliferation of bone
marrow plasma cells and subsequent hypercalcemia, renal dysfunction, anemia, or
bone disease, which remains incurable despite novel emerging therapeutic
strategies. Notably, increasing evidence supports the capability of dietary
natural compounds to antagonize multiple myeloma growth in preclinical models of
human multiple myeloma, underscoring their potential as candidate anti-cancer
agents. In this review, we aim at summarizing findings on the anti-tumor activity
of dietary natural products, focusing on their molecular mechanisms, which
include inhibition of oncogenic signal transduction pathways and/or epigenetic
modulating effects, along with their potential clinical applications against
multiple myeloma and its related bone disease.
PMID- 29956611
TI - Electrophysiological characteristics of the migraine brain: current knowledge and
perspectives.
AB - BACKGROUND: Despite pain being its most prominent feature, migraine is primarily
a disorder of sensory processing. Electrophysiology-based research in the field
has consistently developed over the last fifty years. OBJECTIVE: To summarize the
current knowledge on the electrophysiological characteristics of the migraine
brain, and discuss perspectives. METHODS: We critically reviewed the literature
on the topic to present and discuss articles selected on the basis of their
significance and/or novelty. Results Physiologic fluctuations within time,
between-subject differences, and methodological issues account as major
limitations of electrophysiological research in migraine. Nonetheless, several
abnormalities revealed through different approaches have been described in the
literature. Altogether, these results are compatible with an abnormal state of
sensory processing. PERSPECTIVES: The greatest contribution of
electrophysiological testing in the future will most probably be the
characterization of sub-groups of migraine patients sharing specific
electrophysiological traits. This should serve as strategy towards personalized
migraine treatments. Incorporation of novel methods of analysis would be
worthwhile.
PMID- 29956612
TI - Development and Application of Computational Methods in Phage Display Technology.
AB - BACKGROUND: Phage display is a powerful and versatile technology for the
identification of peptide ligands binding to multiple targets, which has been
successfully employed in various fields, such as diagnostics and therapeutics,
drug-delivery and material science. The integration of next generation sequencing
technology with phage display makes this methodology more productive. With the
widespread use of this technique and the fast accumulation of phage display data,
databases for these data and computational methods have become an indispensable
part in this community. This review aims to summarize and discuss recent progress
in the development and application of computational methods in the field of phage
display. METHODS: We undertook a comprehensive search of bioinformatics resources
and computational methods for phage display data via Google Scholar and PubMed.
The methods and tools were further divided into different categories according to
their uses. RESULTS: We described seven special or relevant databases for phage
display data, which provided an evidence-based source for phage display
researchers to clean their biopanning results. These databases can identify and
report possible target-unrelated peptides (TUPs), thereby excluding false
positive data from peptides obtained from phage display screening experiments.
More than 20 computational methods for analyzing biopanning data were also
reviewed. These methods were classified into computational methods for reporting
TUPs, for predicting epitopes and for analyzing next generation phage display
data. CONCLUSION: The current bioinformatics archives, methods and tools reviewed
here have benefitted the biopanning community. To develop better or new
computational tools, some promising directions are also discussed.
PMID- 29956613
TI - Cancer-associated cachexia, reactive oxygen species, and nutrition therapy.
AB - Cancer-related cachexia (CAC) is a syndrome occurring in many cancer patients,
with a detrimental effect on their survival. Recent reports have outlined that
the syndrome may be partly explained by the deleterious and pro-inflammatory
action of reactive oxygen species (ROS). This review focuses on nutrients that
theoretically could counteract the oxidative stress in tumor cells, fundamentally
due to their antioxidant activity. The preclinical and clinical results obtained
with the nutritional elements selenium, melatonin, taurine, carnosine, coenzyme
Q10 (ubiquinone), and omega-3 polyunsaturated fatty acids (PUFA's) are
discussed in the light of the pathophysiology of CAC. This should indicate that
they are viable candidates for the treatment of CAC, with the ultimate goal to
promote patient survival. Combination therapy with diet modification added to the
novel pharmaceutical agent ghrelin, a hormone with anti-inflammatory properties,
represents a promising concept.
PMID- 29956614
TI - Latest Updates in Dengue Fever Therapeutics: Natural, Marine, and Synthetic
Drugs.
AB - In this paper, we review the history of Dengue, the mechanism of infection, the
molecular characteristics and components of Dengue, the mechanism of entry to the
target cells, cyclization of the genome and replication process, as well as
translation of the proteins for virus assembly. The major emphasis of this work
is on natural products and plant extracts, which were used for as palliative or
adjuvant treatment of Dengue. This review article also summarizes latest findings
in regards to the marine products as effective drugs to target different symptoms
of Dengue. Furthermore, an update on synthetic drugs for treating Dengue is
provided in this review. As a novel alternative, we describe monoclonal antibody
therapy for Dengue management and treatment.
PMID- 29956615
TI - Roles of Cyclooxygenase, Prostaglandin E2 and EP Receptors in Mucosal Protection
and Ulcer Healing in the Gastrointestinal Tract.
AB - Endogenous prostaglandins (PGs), produced from arachidonic acid by the two
isoforms of cyclooxygenase (COX), play a pivotal role in maintaining mucosal
integrity by modulating various functions of the gastrointestinal (GI) tract, and
PGE2 is most effective in these actions. The PGE2 receptor is classified into 4
specific G-protein coupled subtypes, EP1-EP4, and their distribution accounts for
the multiple effects of this prostanoid. PGE2 prevents acid-reflux esophagitis
and indomethacin-induced gastric lesions through EP1 receptors, while endogenous
PGs protect the stomach against cold restraint stress mediated by mainly PGI2/IP
receptors and partly EP4 receptors. PGE2 also exhibits a protective effect
against acid-induced duodenal damage and indomethacin-induced small intestinal
lesions mediated by EP3/EP4 receptors; these effects in the stomach, duodenum, or
small intestine are associated functionally with inhibition of gastric
contraction (EP1), stimulation of duodenal HCO3 - secretion (EP3/EP4), or
suppression of bacterial invasion due to the inhibition of intestinal motility
(EP4) as well as stimulation of mucus secretion (EP3/EP4), respectively. PGE2
also prevents ischemiainduced enteritis and dextran sulfate sodium-induced
colitis mediated by EP4 receptors, and the protective mechanisms may be related
to the stimulation of mucus secretion and the down-regulation of immune response,
respectively. Furthermore, PGE2 shows a healing-promoting effect on gastric
ulcers and small intestinal lesions through the up-regulated expression of
vascular endothelial growth factor (VEGF) and stimulation of angiogenesis via the
activation of EP4 receptors. Finally, COX-1 is mainly responsible for the
production of endogenous PGs involved in mucosal protection, while COX-2 is
mainly responsible for those involved in the healing of gastric ulcers or small
intestinal lesions. These findings contribute to future development of new
strategies for the treatment of GI diseases.
PMID- 29956616
TI - Process Analytical Technology for Crystallization of Active Pharmaceutical
Ingredients.
AB - BACKGROUND: Pharmaceutical industry is witnessing increased pressure to introduce
innovative and efficient processes for manufacturing Active Pharmaceutical
Ingredients (APIs) in order to be competitive as well as to meet the stringent
product quality requirements set by regulatory authorities. Crystallization with
its ability to engineer the final product to the desired qualities such as
purity, polymorphic form, particle size and shape is one of the most important
steps involved in the manufacturing of APIs. Therefore, development of
crystallization processes with better understanding of process parameters and
their impact on quality of APIs and subsequently the drug products assume great
significance for the pharmaceutical industry. METHODS: This review paper focuses
on the application of PAT tools, an integral part of Quality by Design (QbD)
approach, for better understanding, control, and design of crystallization
processes in the manufacturing of APIs. RESULTS: Firstly, various steps involved
in the drug development process are introduced briefly with emphasis on
crystallization as one of the most important steps in manufacturing of drug
products. Secondly, Critical Quality Attributes (CQAs) of drug products, their
dependence on material attributes of APIs and role of crystallization in
manipulating material attributes of APIs has been discussed. Finally, application
of PAT tools such as advanced process analyzers for continuous monitoring,
chemometric methods for multivariate data analysis, and control strategy for APIs
crystallization processes has been reviewed along with some examples. CONCLUSION:
Application of PAT in crystallization of APIs facilitates development of robust
processes that works within the design space to produce the drug products of
consistent quality. Furthermore, it opens up the opportunities for continuous
improvement of the process by generating knowledge base of existing processes.
PMID- 29956617
TI - Exploring the Benefits of Cellular Models to Uncover Bioactive Polyphenols for
Neurodegeneration.
AB - Our society is currently experiencing increased lifespan; one of the top causes
for the high incidence of neurodegenerative disorders. The lack of effective
treatments delaying or blocking disease progression has encouraged the active
search for novel therapies. Many evidences support the protective role of
phytochemicals in the prevention of neurodegenerative diseases, particularly
(poly)phenols. In this review, we described the use of cellular-based models of
neurodegenerative diseases and the benefits of their use as potent tools in the
search for bioactive molecules, particularly (poly)phenols. Studies to assess the
biological activity of (poly)phenols involve experimentation with in vitro and in
vivo systems. In vitro systems are a useful tool as a first approach to test the
underlined molecular mechanisms of candidate molecules. They can provide valuable
information about biological activity, which can be then used to design animal
and human intervention studies.
PMID- 29956618
TI - Metabolism of Peptide Drugs and Strategies to Improve their Metabolic Stability.
AB - BACKGROUND: Despite the therapeutic use of peptides is limited because of their
metabolism in vivo, there are no systematic reviews explaining degradation of
peptides by peptidases. This review summarizes peptidases present in the tissues
and metabolic characteristics of peptides, and provides recent strategies for
improving the metabolic stability of peptides. METHOD: We reviewed a number of
peptidases including their functional groups, tissue localization and cleavage
specificity. Given the broad distribution of peptidases in the body, several
tissues, such as the liver, kidney, lung, blood, nasal epithelial cells, placenta
and skin, have the capacity to metabolize peptides. We compared the metabolic
characteristics of peptides in these tissues and then summarized strategies for
improving peptide stability. RESULTS: In addition to the primary organs including
liver, kidney, gastrointestinal tract and blood involved in peptide metabolism,
other organs such as the lung, skin, placenta and nasal mucosa may also play a
role in peptide degradation. At present, the main measures to improve the
stability of the peptide include N- and/or C-terminal modification or
substitution, D-amino acid or unnatural amino acid substitution, cyclization,
backbone modification, nanoparticle formulations and increased molecular mass.
CONCLUSION: This review summarized the key in vivo peptidases and their tissue
distribution characteristics, and presented strategies to improve the metabolic
stability and bioavailability of peptide drugs. These viewpoints will benefit the
further development and utilization of peptide drugs.
PMID- 29956619
TI - Current Designs of Polymer Blends in Solid Dispersions for Improving Drug
Bioavailability.
AB - BACKGROUND: Ternary solid dispersions have been demonstrated to be an effective
strategy in the improvement of drug absorption and bioavailability. METHOD: The
applications of the combination of hydrophilic polymers with the potential of
hydrophobic polymer incorporation at moderate concentrations have been discussed
in recent publications. RESULTS: In this paper, the general review of this
specific type of solid dispersion will be provided with comprehensive
understanding of polymer blends of either hydrophilic or hydrophobic polymers. A
detailed description of miscible polymers has been developed in recent studies.
In addition to dissolution rate improvement, the role of second polymers in
crystal growth inhibition and in maintaining the amorphous state will be
mentioned. CONCLUSION: We also present a summary of characterization techniques
commonly used to evaluate solid dispersion and polymer miscibility.
PMID- 29956620
TI - Total Sleep Duration and Risk of Type 2 Diabetes: Evidence-Based On Clinical and
Epidemiological Studies.
AB - BACKGROUND: Increasing incidences of type 2 diabetes make it necessary to have a
better understanding of the risk factors for its prediction. Taking a note of
resilience in risk factors, dynamics of the emerging factors other than
traditional ones are showing a great interest in recent years which imprints a
significant contribution in the occurrence of diabetes. Of different factors,
sleep duration was acknowledged as a most common risk factor for diabetes.
METHODS: Adhering to the state of information available, studies recruited
between 2010- 2016 a total of seven prospective studies including systematic
review and meta-analysis were used to establish the relationship between sleep
duration and type 2 diabetes. Studies were identified from Medline and Scopus.
Studies included in this review was considered based on the different aspects
such as maximum follow-up period, number of participants, including both sexes
along with similar reference criteria of sleep duration. RESULTS: With U-shaped
association between sleep duration and the onset of diabetes, both short and long
term sleep duration was found contributing to the development of type 2 diabetes.
Additionally, studies on the sex-related difference and pervasiveness of diabetes
have also reported a profound relationship between short and long sleep hours and
risk of developing type 2 diabetes. CONCLUSION: Our study supports other studies
on the relationship between total sleep duration and the risk of developing type
2 diabetes. This review emphasizes the importance of total sleep duration, sleep
quality as a risk marker in monitoring type 2 diabetes.
PMID- 29956621
TI - The Pharmacogenomics of Asthma beyond its Endotypes.
AB - Asthma is a heterogeneous disease that consists of different phenotypes and
endotypes, driven by different mechanistic pathways. An increasing number of
genetic loci and single-nucleotide polymorphisms have been associated with
therapeutic responses to asthma drugs. The purpose of this review is to focus on
certain susceptibility genes, gene variants and typical therapeutic drugs of the
glucocorticoid, leukotriene, histamine, and beta2-adrenergic receptor pathways
related to asthma. Pharmacogenomics can help us better understand the genetic
basis of drug responses and better define new therapeutic targets to improve
treatment effectiveness.
PMID- 29956622
TI - Diverse Therapeutic Potential of Nitidine, A Comprehensive Review.
AB - BACKGROUND: Nitidine is a bioactive plant benzophenanthridine alkaloid isolated
from the root of Zanthoxylum nitidum. Since its discovery in 1959, literature
revealed marked anticancer, neuroprotective, antimalarial, anti-HIV, analgesic,
anti-inflammatory and antifungal activities. However, its clinical status is not
defined yet. METHODS: Various scientific search engines were used for the
available literature All the peer-reviewed journals were considered in this
review. MOE (molecular operating environment) ligand-based pharmacophores
features of nitidine were also studied to determine the various targeted sites in
the molecule. RESULTS: The search revealed an outstanding therapeutic potential
in terms of various pharmacological effects of the molecule. MOE (Molecular
Operating Environment) ligand-based pharmacophores features of nitidine showed
that it has got multiple bioactive functional sites that implicate its
sensitivity towards several receptors protein and therefore could be a useful
lead compound. Despite having an outstanding therapeutic potential, it is not
subjected to clinical trial yet, probably, due to host toxicity and being a
quaternary salt, charged at all body pH values, and therefore, absorption through
the gastro-intestinal-tract could be an issue. CONCLUSION: The issues can be
resolved while applying latest pharmaceutical technologies, synthesizing its
derivatives and subsequent clinical studies and thus could lead to the discovery
of new clinically effective molecule(s).
PMID- 29956623
TI - Genetic Polymorphism on the Pharmacokinetics and Pharmacodynamics of Platelet
derived Growth Factor Receptor (PDGFR) Kinase Inhibitors.
AB - Platelet-derived Growth Factor Receptor (PDGFR) is one of the families of
Receptor Tyrosine Kinases (RTKs), which have attracted increasing attention as a
potential target of antitumor therapy in cancer. PDGFR family members consist of
PDGFR-alpha, PDGFR-beta, CSF-1R, KIT and FLT3. Tyrosine Kinase Inhibitors (TKIs)
are a kind of small molecule inhibitors targeting RTKs. TKIs prevent and block
vital pathways by targeting signaling molecules which are necessary for cell
survival. At present, about 11 kinds of TKIs targeting PDGFR family members have
been approved for the treatment of diseases like chronic myelogenous leukemia
(CML), gastrointestinal stromal tumors (GIST), renal cell carcinoma (RCC), etc.
This review focuses on 11 PDGFR kinase inhibitors, including imatinib, sunitinib,
regorafenib, sorafenib, pazopanib, axitinib, dasatinib, nilotinib, lenvatinib,
cabozantinib and ponatinib. This article also provides an overview of: (1)
general information on PDGFR kinase inhibitors; (2) pharmacokinetic parameters of
PDGFR kinase inhibitors; (3) metabolic enzymes and transporters of PDGFR kinase
inhibitors; (4) main drug interactions of PDGFR kinase inhibitors; (5) adverse
events of PDGFR kinase inhibitors; and (6) genetic polymorphism on
pharmacokinetics and pharmacodynamics of PDGFR kinase inhibitors.
PMID- 29956624
TI - Relevance of Breast Cancer Resistance Protein to Brain Distribution and Central
Acting Drugs: A Pharmacokinetic Perspective.
AB - BACKGROUND: Breast Cancer Resistance Protein (BCRP, also known as ABCG2) is
gaining momentum as a key transporter that restricts the permeability of a large
number of therapeutic agents through the Blood-brain Barrier (BBB). BCRP is
highly expressed in the apical membranes of epithelial cells of the small and
large intestine, renal proximal tubules and canalicular membrane of hepatocytes,
determining the gastrointestinal absorption and biodisposition of its substrates.
It is also expressed in the luminal surface of endothelial cells of the BBB and
Bloodspinal Cord Barrier (BSCB), where it undoubtedly limits the entry of a wide
range of therapeutics into the CNS, potentially contributing to the therapeutic
failure of CNS-acting drugs. METHODS: As the U.S. Food and Drug Administration
and the European Medicines Agency recommend pre-clinical evaluation and clinical
assessment of BCRP-mediated drug-drug interactions, compounds that are currently
recognized as BCRP substrates, inhibitors or inducers will be addressed, focusing
on their pharmacokinetic behaviour in plasma and brain. RESULTS: Recent studies
indicated a strong BCRP expression in the microvasculature of the BBB in brain
tumors, hypothesizing that this phenomenon critically influences the penetration
of drugs in these tumors and potentially contributes to the failure of antitumor
therapy. BCRP expression in brain tissue from patients or animal models of
neurological and neurodegenerative diseases has also been investigated, and the
role of BCRP and its implications for novel therapeutic interventions was also
herein demonstrated. CONCLUSIONS: The clinical significance of BCRP in drugs
disposition is currently undeniable.
PMID- 29956625
TI - Luteolin Regulates Macrophage Polarization via the PI3K/Akt Pathway to Inhibit
the Apoptosis Stimulated by Angiotensin II.
AB - BACKGROUND: The aim of this study was to investigate anti-apoptotic effects of
luteolin on angiotensin II-stimulated murine peritoneal macrophages and to
explore its mechanisms. METHODS AND RESULTS: The viability and cytotoxicity of
murine peritoneal macrophages were assessed using the Cell Counting Kit-8 assay
and measuring lactate dehydrogenase levels, respectively. Apoptotic rates were
determined using Annexin V/propidium iodide staining. Protein expression was
examined by western blotting, and markers of macrophage phenotypes were analyzed
by flow cytometry and ELISA. Luteolin decreased the apoptotic rate of angiotensin
II-stimulated macrophages. This effect was associated with increased Bcl-2 and
caspase-3 levels as well as decreased Bax and cleaved caspase-3 levels.
Additionally, luteolin reduced the expression of M1 macrophage phenotype markers
(IL-6, TNF-alpha, iNOS, CD16/32) and increased the expression of M2 macrophage
phenotype markers (Dectin-1, IL-10, Arg-1, CD206). Moreover, luteolin blocked Akt
phosphorylation on residues 308 and 473, which were up-regulated in presence of
angiotensin II. The effects of luteolin were similar to those of LY294002, a
specific PI3K/Akt pathway inhibitor. CONCLUSIONS: These results indicated that
luteolin has anti-apoptotic effects on angiotensin II-stimulated macrophages via
macrophage polarization, which might be associated with PI3K/Akt signaling.
PMID- 29956626
TI - Biotechnological Approaches for the Production of Pharmaceutically Important
Compound: Plumbagin.
AB - BACKGROUND: Increased demand for compounds that are derived from natural source
are gaining more and more importance. Plumbagin is a plant naphthoquinone which
is present in several families, including Iridaceae, Plumbaginaceae, Ebenceae,
Drosophyllaceae, Nepenthaceae and Droseraceae. Plumbagin possesses high
therapeutic efficacy and minimal side effects. It has various pharmaceutical
activities which include anticancer, antibacterial, anti-inflammatory,
antioxidant, antifungal, neuroprotective and hypolipidemic activities. In natural
habitat, production of plumbagin is low due to species variations and
environmental changes, considering importance of this bioactive compound,
alternative techniques for its enhanced production needs to be devised. In the
present review, various production techniques and scale-up strategies for
plumbagin production are discussed. OBJECTIVES: Aim of this review is to provide
an insight into the chemistry of plumbagin, its pharmaceutical activities,
perspective of cell suspension culture, root culture, hairy root culture and
scale up strategies for its production. METHODOLOGY: All the data compiled and
presented here were obtained from various E-resources like Pubmed, Science
Direct, and Google Scholar up to February 2018. RESULT: This review comprises
isolation, extraction and quantification method for plumbagin, its pharmaceutical
activities, various tissue culture production techniques and scale-up strategies
for enhanced production. CONCLUSION: Plumbagin is an important phytocompound
which shows potential towards treatments of various diseases. Demand for the
production of plumbagin continuously increasing worldwide due to its
pharmacological properties. To fulfil commercial demand of plumbagin alternative
technologies need to be investigated. Biotechnological approaches like cell
suspension culture, root suspension culture and hairy root culture are
alternative techniques for plumbagin production. These techniques provide
continuous supply of bioactive compounds. However, research on various aspects of
tissue culture production techniques is in preparatory stage and requires culture
and process optimization for development of a commercially practical process.
PMID- 29956627
TI - Pharmacological Effects and Chemical Constituents of Bupleurum.
AB - Radix Bupleuri is commonly used in traditional Chinese medicine for thousands of
years with confirmed curative effects. Except for medicine, it is also used in
healthy food, and cosmetics for its specifc activities. Therefore, the chemical
constituents, mainly including flavonoids, lignins, Phenyl propanol derivatives,
triterpenoid saponins, and volatile oils, and pharmacological effects have been
well studied by many scholars in recent years and a comprehensive and systematic
review on chemical constituents and pharmacological effects of Radix Bupleuri is
indispensable. This paper aims at reviewing the chemical components and
pharmacological effects of Radix Bupleuri in recent years through searching for
the literatures both at home and abroad. Our results show that diverse
pharmacological effects and more than 281components have been isolated from Radix
Bupleuri, including 15 flavonoids, 430 lignins, 12 Phenyl propanol derivatives,
66 triterpenoid saponins, and 158 volatile oils, which could lay a foundation for
the further application of Radix Bupleuri.
PMID- 29956628
TI - Interactions of vascular endothelial growth factor and p53 with miR-195 in
thyroid carcinoma: possible therapeutic targets in aggressive thyroid cancers.
AB - BACKGROUND: The clinical pathological features as well as the cellular mechanisms
of miR-195 have not been investigated in thyroid carcinoma. OBJECTIVE: The aim of
this study is to identify the interactions of vascular endothelial growth factor
(VEGF), p53 and miR-195 in thyroid carcinoma. The clinical and pathological
features of miR-195 were also investigated. METHOD: The expression levels of miR
195 were identified in 123 primary thyroid carcinomas, 40 lymph nodes with
metastatic papillary thyroid carcinomas and seven non-neoplastic thyroid tissues
(controls) as well as two thyroid carcinoma cell lines, B-CPAP (from
metastasizing human papillary thyroid carcinoma) and MB-1 (from anaplastic
thyroid carcinoma), by the real-time polymerase chain reaction. Using Western
blot and immunofluorescence, the effects of exogenous miR-195 on VEGF-A and p53
protein expression levels were examined. Then, cell cycle and apoptosis assays
were performed to evaluate the roles of miR-195 in cell cycle progression and
apoptosis. RESULTS: The expression of miR-195 was downregulated in majority of
the papillary thyroid carcinoma tissue as well as in cells. Introduction of
exogenous miR-195 resulted in downregulation of VEGF-A and upregulation of p53
protein expressions. Upregulation of miR-195 in thyroid carcinoma cells resulted
in cell cycle arrest. Moreover, we demonstrated that miR-195 inhibits cell cycle
progression by induction of apoptosis in the thyroid carcinoma cells. CONCLUSION:
Our findings showed for the first time that miR-195 acts as a tumour suppressor
and regulates cell cycle progression and apoptosis by targeting VEGF-A and p53 in
thyroid carcinoma. The current study exhibited that miR-195 might represent a
potential therapeutic target for patients with thyroid carcinomas having
aggressive clinical behaviour.
PMID- 29956629
TI - Challenges and opportunities from basic cancer biology for nanomedicine for
targeted drug delivery.
AB - BACKGROUND: Effective cancer therapy is still a great challenge for modern
medical research due to the complex underlying mechanisms of tumorigenesis and
tumor metastasis, and the limitations commonly associated with currently used
cancer therapeutic options. Nanotechnology has been implemented in cancer
therapeutics with immense potential for improving cancer treatment. OBJECTIVES:
Through information about the recent advances regarding cancer hallmarks, we
could comprehensively understand the pharmacological effects and explore the
mechanisms of the interaction between the nanomaterials, which could provide
opportunities to develop mechanism-based nanomedicine to treat human cancers
through. METHODS: We collected related information and data from articles.
RESULTS: In this review, we discussed the characteristics of cancer including
tumor angiogenesis, abnormalities in tumor blood vessels, uncontrolled cell
proliferation markers, multidrug resistance, tumor metastasis, cancer cell
metabolism, and tumor immune system that provide opportunities and challenges for
nanomedicine to be directed to specific cancer cells and portray the progress
that has been accomplished in application of nanotechnology for cancer treatment.
CONCLUSION: The information presented in this review can provide useful
references for further studies on developing effective nanomedicine for treatment
of cancer.
PMID- 29956630
TI - Formulation, pharmacokinetic evaluation and cytotoxicity of an enhanced
penetration paclitaxel nanosuspension.
AB - BACKGROUND: Improving poorly soluble drugs into druggability was a major problem
faced by pharmaceutists. Nanosuspension can improve the druggability of insoluble
drugs by improving the solubility, chemical stability and reducing the use of
additives, which provided a new approach for the development and application of
the insoluble drugs formulation. Paclitaxel (PTX) is a well-known BCS class IV
drug with poor solubility and permeability. Also, many studies have proved that
paclitaxel is a substrate of the membrane-bound drug efflux pump P-glycoprotein
(P-gp), therefore it often shows limited efficacy against the resistant tumors
and oral absorption or uptake. OBJECTIVE: To manufacture an enhanced-penetration
PTX nanosuspension (PTX-Nanos), and evaluate the physicochemical property,
pharmacokinetics and tissue distribution in vivo and cytotoxic effect in vitro.
METHOD: PTX-Nanos were prepared by microprecipitation-high pressure
homogenization, with a good biocompatibility amphiphilic block copolymer poly(L
phenylalanine)-b-poly(L-aspartic acid) (PPA-PAA) as stabilizer. RESULTS: The PTX
Nanos had a sustained-dissolution manner and could be effectively reduce plasma
peak concentration and extend plasma circulating time as compared to PTX
injection, markedly passively target to the MPS-related organs, such as liver and
spleen. This unique property might enhance treatment of cancer in these tissues
and reduce the side effects in other normal tissues. Moreover, the hybrid
stabilizers could enhance penetration of PTX in PTX-Nanos to multidrug resistance
cells. CONCLUSION: To sum up, our results showed that the optimal formula could
improve the solubility of PTX and the stability of the product. The PTX-Nanos
developed in this research would be a promising delivery platform in cancer
treatment.
PMID- 29956631
TI - Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic
Seizures and Epileptogenesis.
AB - A burgeoning literature documents the confluence of ovarian steroids and central
serotonergic systems in the injuction of epileptic seizures and epileptogenesis.
Estrogen administration in animals reduces neuronal death from seizures by up
regulation of the prosurvival molecule i.e. Bcl-2, anti-oxidant potential and
protection of NPY interneurons. Serotonin modulates epileptiform activity in
either direction i.e administration of 5-HT agonists or reuptake inhibitors leads
to activation of 5-HT3 and 5-HT1A receptors tending to impede focal and
generalized seizures, while depletion of brain 5-HT along with destruction of
serotonergic terminals leads to expanded neuronal excitability hence abatement of
seizure threshold in experimental animal models. Serotonergic neurotransmission
is influenced by the organizational activity of steroid hormones in growing brain
and the actuation effects of steroids which come in adulthood. It is further
established that ovarian steroids bring induction of dendritic spine
proliferation on serotonin neurons thus thawing a profound effect on serotonergic
transmission. This review features 5-HT1A and 5-HT3 receptors as potential
targets for ameliorating seizure induced neurodegeneration and recurrent
hypersynchronous neuronal activity. Indeed 5-HT3 receptors mediate cross talk
between estrogenic and serotonergic pathways, and could well be exploited for
combinatorial drug therapy against epileptogenesis.
PMID- 29956632
TI - Role of estradiol in the expression of genes involved in serotonin
neurotransmission: Implications for female depression.
AB - BACKGROUND: In women, changes in estrogen levels may increase incidence and/or
symptomatology of depression and affect the response to antidepressant
treatments. Estrogen therapy in females may provide some mood benefits as a
single treatment, or might augment clinical response to antidepressants that
inhibit serotonin reuptake. OBJECTIVE: We analyzed the mechanisms of estradiol
action involved in the regulation of gene expression that modulate serotonin
neurotransmission implicated in depression. METHOD: Publications were identified
by a literature search on PubMed. RESULTS: The participation of estradiol in
depression may include regulation of the expression of tryptophan hydroxylase-2,
monoamine oxidase A and B, serotonin transporter and serotonin-1A receptor. This
effect is mediated by estradiol binding to intracellular estrogen receptor that
interacts with estrogen response elements in the promoter sequences of tryptophan
hydroxylase-2, serotonin transporter and monoamine oxidase-B. In addition to
directly binding deoxyribonucleic acid, estrogen receptor can tether to other
transcription factors, including activator protein 1, specificity protein 1,
CCAAT/enhancer binding protein beta and nuclear factor kappa B to regulate gene
promoters that lack estrogen response elements, such as monoamine oxidase-A and
serotonin 1A receptor. CONCLUSION: Estradiol increases tryptophan hydroxylase-2
and serotonin transporter expression and decreases the expression of serotonin 1A
receptor and monoamine oxidase A and B through the interaction with its
intracellular receptors. The understanding of molecular mechanisms of estradiol
regulation on the protein expression that modulates serotonin neurotransmission
will be helpful for development of new and more effective treatment for women
with depression.
PMID- 29956633
TI - Statins and elderly: from clinical trials to daily practice.
AB - Elderly patients represent a rising social problem, due to the exponential growth
of persons in these age groups and their atherothrombotic burden. The management
of this population still raises several challenges, requiring a balance between
elevated cardiovascular risk, clinical complexity, frailty and co-morbidities.
Statins represent a main pillar in cardiovascular prevention, lowering serum
cholesterol and reducing mortality and ischemic events, especially in high-risk
patients. Yet, elderly patients have often been excluded from major clinical
trials of statins, thus limiting the experience with these drugs in advanced age.
Moreover, important barriers to the use of statins in the elderly exist due to
potential risks attributed to altered metabolism, comorbidities, polypharmacy and
drug-drug interactions and financial constraints. This situation has led to a
"statin paradox", since high-risk elderly patients that would most benefit from
the use of statins, may be undertreated with these drugs in real life. The vague
indications provided by guidelines mean that this issue is still debated,
especially regarding primary prevention. Nevertheless, the benefits in outcome
offered by statins cannot be neglected. Efforts should be made in order to focus
on the importance of statin use in the elderly and to provide clinicians with
adequate tools for case by case decisions.
PMID- 29956634
TI - Association of serum homocysteine level and lung involvement in systemic
sclerosis.
AB - BACKGROUND: Systemic sclerosis (SSc) is a disorder of connective tissue affecting
the skin and internal organs, characterized by fibrotic changes of peripheral and
visceral architecture. OBJECTIVE: We investigated the correlation between serum
concentration of homocysteine and interstitial lung involvement in SSc patients.
METHOD: Fifty nine patients with SSc (53 females and 6 males) with a mean age of
43.34 years (range: 17-76 years) were enrolled. Patients were divided into case
(33 patients) and control (26 patients) groups based on the presence or absence
of interstitial lung involvement (abnormal pulmonary function test and chest High
resolution computed tomography). Group cases comprised the patients with lung
involvement (36 cases). We also divided the patients into diffuse cutaneous
(dcSSc) type (39 case) and limited cutaneous (lcSSc) type (20 case). Serum
homocysteine, vitamin B12, and folate levels were measured. RESULTS: Mean serum
homocysteine level in the all study population was13.74+/-6.03MUmol/L.
Homocysteine level was not significantly different between the case and control
groups (mean serum homocysteine level in the cases was 13.44+/-5.48MUmol/L and in
the controls it was 14.24+/-7.89MUmol/L). Mean serum homocysteine level in the
dcSSc type and lcSSc type was 13.8564+/-6.66MUmol/L and 13.68+/-6.66MUmol/L,
respectively, but this difference was not significant between the two types of
SSc. CONCLUSION: This study manifested that serum homocysteine level did not
differ between the scleroderma type; also, we found no statistically significant
correlation between the serum homocysteine level and interstitial lung
involvement in SSc patients. It seems that the serum level of homocystein has a
minor role in the lung involvement of SSc patients or its effects are modified by
other factor.
PMID- 29956635
TI - Lead molecule prediction and characterization for designing MERS-CoV 3C-like
protease inhibitors: an in silico approach.
AB - BACKGROUND: 3C-like protease also called the main protease is an essential enzyme
for the completion of the life cycle of Middle East Respiratory Syndrome
Coronavirus. In our study we predicted compounds which are capable of inhibiting
3C-like protease,and thus inhibit the lifecycle of Middle East Respiratory
Syndrome Coronavirus using in silico methods. METHODS: Lead like compounds and
drug molecules which are capable of inhibiting 3C-like protease was identified by
structure-based virtual screening and ligand-based virtual screening method.
Further, the compounds was validated through absorption, distribution, metabolism
and excretion filtering. RESULTS: Based on binding energy, ADME properties, and
toxicology analysis, we finally selected 3 compounds from structure-based virtual
screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy
7.12, -7.1 and -7.08 Kcal/mol respectively and 5 compounds from ligand-based
virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324)
having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively.
All these compounds have good ADME profile and reduced toxicity. Among eight
compounds, one is soluble in water and remaining 7 compounds are highly soluble
in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among
the 5 compounds from structure-based virtual screening, 2 compounds showed
leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes,
no blood-brain barrier permeability and no toxic structure in medicinal chemistry
profile. All the compounds are not a substrate of P-glycoprotein. CONCLUSION: Our
predicted compounds may be capable of inhibiting 3C-like protease but need some
further validation in wet lab.
PMID- 29956636
TI - Application of Electrospinning Strategy on Cartilage Tissue Engineering.
AB - Cartilage, constituted with a relatively hypocellular structure and lacking of
neural and vascular connections, is not a well self-repairing tissue. Cartilage
tissue engineering involving bulk of biomaterials has been put forward as a
strategy for articular cartilage lesions. The most complicated issue for
cartilage repairing is to simulate the highly hierarchical structure,
extracellular matrix (ECM) composition and even mechanical features.
Electrospinning can produce flexible, dense fibrous membranes with moderate
mechanical properties and biological features with different constitution of
polymer, orientation, diameter and morphology of fibers, or cooperation forms
with other strategies. In our review, four classes are mentioned for cartilage
tissue engineering and kinds of biomaterials to be utilized.
PMID- 29956638
TI - Design, Graph Theoretical Analysis and Insilico Modeling of Dunaliella bardawil
Biomass Encapsulated N-Succinyl Chitosan Nanoparticles for Enhanced Anticancer
Activity.
AB - PURPOSE: To investigate N-succinyl chitosan nanoparticles (NSC NPs) encapsulation
with Dunaliella bardawil (D. bardawil) biomass for high utilization enhanced
effectiveness and least side effects for anticancer activity. METHODS: The
potential bioactive compounds from D. bardawil biomass was encapsulate NSC NPs by
ionotropic gelation method and to characterize its molecular shape, particle
size, stability and polydispersity index using FTIR, XRD, SEM, TEM and Zetasize
Nano analyzer. Signaling pathway analysis, molecular docking study and in vitro
anticancer screening were performed on chosen H-Ras P21, 721P and liver cancer
cell lines (HepG2) respectively. RESULTS: The D. bardawil biomass majorly
contains 6 bioactive compounds such as beta-carotene, lutein, zeaxanthin,
phytoene, canthaxanthin, and phytofluene were identified by LC-MS. The D.
bardawil biomass encapsulated NSC NPs showed an average particle size of 80+/-5.6
nm in spherical shape, crystalline nature, zeta potential of -32+/-2.7 mV and
polydispersity index of 0.51+/-0.02. Interestingly, the identified target using
graph theoretical signaling pathway analysis and molecular docking study showed
strong interaction of NSC NPs in binding pockets of H-Ras P21 protooncogene. At
50ug/mL, NPs displayed 95.60% cytotoxicity in HepG2 cell line. The apoptotic cell
cycle analysis showed cell death for 24 h and 48 h representing 13.13% and 47.04%
respectively. CONCLUSION: The highly cross-linked, biocompatible, biodegradable,
nontoxic NSC NPs promising carrier for delivery of bioactive molecules present in
the D. bardawil biomass was found to be actively involved in deregulation of
cellular growth in targeted cancer cells. Thus active NPs serve as a novel
nanodrug to enhance the controlled; site specific drug delivery in the management
of cancer.
PMID- 29956637
TI - CS5931, A Novel Marine Polypeptide, Inhibits Migration and Invasion of Cancer
Cells Via Interacting with Enolase 1.
AB - BACKGROUND: CS5931, a novel marine peptide, was extracted and purified from the
sea squirt Ciona savignyi. Our previous studies showed that recombinant CS5931
can significantly inhibit tumor growth both in vitro and in vivo. However, its
molecular targets have not been elucidated. METHODS: The target of the
recombinant CS5931 was identified by pull-down/SDS-PAGE/MS approaches and
confirmed by Western blot and surface plasmon resonance analysis. Transwell
experiments were used to detect whether the recombinant CS5931 inhibited cancer
migration and invasion via enolase 1. Dot blotting analysis was used to detect
the effect of CS5931 on the interaction of enolase 1 and plasminogen, as well as
enolase 1 and uPA/uPAR. RESULTS: Enolase 1 was identified as the molecular target
interacting with the recombinant CS5931. Transwell experiment showed that the
recombinant CS5931 was able to inhibit migration and invasion of HCT116 cells and
enolase 1 overexpression reversed the effects of the recombinant CS5931 on
migration and invasion of cancer cells. Dot blotting analysis revealed that the
recombinant CS5931 interfered with the interaction among enolase 1 and
plasminogen as well as enolase 1 and uPA/uPAR. CONCLUSION: Our present study
showed that the recombinant CS5931 could inhibit tumor invasion and matastasis
via interacting with enolase 1, suggesting that the new marine polypeptide CS5931
possesses the potential to be developed as a novel anticancer agent.
PMID- 29956639
TI - Albendazole and treatment of hydatid cyst, review of literature.
AB - Human hydatid cyst or cystic echinococcosis is a life-threatening zoonotic
disease that occurs in most countries worldwide and is recognized as a major
public health problem. Following, ingestion of Echinococcus granulosus eggs,
hydatid cysts which is the larval stage of the worm are formed mostly in liver
and lungs, and occasionally in other organs of human. The usual treatment for
hydatid cyst is open surgery. One of the problems, following surgery is the
recurrence. In the last decades albendazole has been used for the treatment of
hydatid cyst. This drug may be used alone or jointly with surgical procedures.
However, its efficacy has not been well documented. Thus, in this work, the
treatment of hydatid cyst with albendazole in different investigations including
case studies, clinical trials in human and experimental works in animals has been
reviewed. According to findings of this review, it can be concluded that
treatment of hydatid cyst with albendazole may be associated with prevention from
recurrence and reduction of the size and death of the hydatid cysts.
PMID- 29956641
TI - Anti-biofilm activity against Gram-positive bacteria by biologically synthesized
silver nanoparticles using Curcuma longa.
AB - OBJECTIVE: To assess the biofilm inhibition activity of biosynthesized silver
nanoparticles (AgNPs) using Curcuma longa. METHODS: Characterizations of these
biogenic nanoparticles were done by UV-Vis spectroscopy, TEM, EDX and
nanoparticles tracking analyzer. Antibiofilm activity of AgNPs against S. aureus
and S. pneumoniae was carried out by 96 well plate method. Further the combined
effect of AgNPs with the antibiotic was studied against S. aureus and S.
pneumoniae. RESULTS: UV-spectroscopic analysis showed a surface plasmon resonance
peak at 415nm. Shape of AgNPs is spherical with average size of 20-40 nm while
the elemental silver was confirmed by EDX analysis. These biosynthesized AgNPs
have anti-biofilm activity against S. aureus and S. pneumoniae. Furthermore, the
combined effect of AgNPs with antibiotic, showed enhanced anti-biofilm activity
against both the strains under study. CONCLUSION: C.longa mediated AgNPs showed
potent antibiofilm activity.
PMID- 29956640
TI - Final Outcome of 223Ra-therapy and the Role of 18F-fluoride-PET in Response
Evaluation in Metastatic Castration-resistant Prostate Cancer-A Single
Institution Experience.
AB - BACKGROUND: 223Ra was the first therapeutic alpha-emitting radionuclide
registered for clinical practice. This radionuclide is targeting actively bone
forming cells, and it is approved for treating metastatic skeletal disease in
prostate cancer. 18F-PET is used to detect skeletal metastatic disease based on
osteoblastic activity. The aim of this study was to analyze, if 18F-PET can be
used assessing the results of 223Ra therapy, and to report final median overall
survival in a total of 773 therapy cycles. METHODS: A 161 men with castration
resistant prostate cancer were included in a single institution study (Protocol#:
PA14-0848) and they received a total of 773 223Ra therapy cycles. RESULTS: The
median overall survival (95% CI) was 12.4 (9.1, 16.1) months in patient
population. Interim Na18F-PET imaging was applied in 14 patients at baseline,
after 3 cycles and after 6 cycles. TLF10 (skeletal disease burden at SUV-values
>10 on Na18F -PET) were calculated in all these PET studies, and there was no
significant association between change in TLF10 after 3 cycles and TLF10 after 6
cycles (p=0.20). CONCLUSION: From these results, we conclude that interim imaging
does not help in assessing the final outcome of 223Ra therapy. The survival
benefit of 223Ra therapy alone is more than a year in a high-risk group of
advanced prostate cancer.
PMID- 29956642
TI - Identification of the Incapacitated Patient in Mass Casualty Events: An
Exploration of Challenges, Solutions, and Barriers.
AB - Increasing scrutiny of the role and actions of emergency responders in the
aftermath of mass casualty events has led to improvements and advances in terms
of treatment and care. However, despite these improvements, the authors have
identified a growing concern relating to the identification of incapacitated
patients and those unable to provide any identifying details, such as pediatric
patients. The use of visual identification and the reliance on personal effects
within the vicinity of a victim, either living or deceased, has resulted in
mistaken identification in a number of major international incidents. The purpose
of this article is to consider whether commonly used scientific methods for
identification of the deceased could and should be broadened to include victims
who are incapacitated and unable to confirm their own identity. The medicolegal
questions that may arise when applying identification methods established for
deceased patients to the living casualty will also be examined. (Disaster Med
Public Health Preparedness. 2018;page 1 of 7).
PMID- 29956643
TI - Pain management practices surrounding lumbar punctures in children: A survey of
Canadian emergency physicians - CORRIGENDUM.
PMID- 29956644
TI - Fear of Falling in Older Adults with Diabetes Mellitus: The IMIAS Study.
AB - ABSTRACTSeveral determinants of developing fear of falling (FoF) overlap with the
consequences of diabetes mellitus (DM). We compared the prevalence and severity
of FoF in older adults with and without DM and identified which FoF determinants
contribute to FoF severity in older adults with DM. We used Canadian baseline
data from the International Mobility in Aging Study (IMIAS) which identified 141
older adults with DM (DM-group;age:68.88+/-2.80years) and 620 without DM (noDM
group;age:68.81+/-2.68years). FoF was quantified with Falls Efficacy Scale
International (FES-I). FoF determinants were evaluated in demographic/health
related, physical, psychological, and social domains. High concern of FoF was
more prevalent and of higher severity in 10/16 FES-I activities in the DM-group
compared to the noDM-group. Higher FoF severity in the DM-group was associated
with poor physical performance, being female, fall history, and clinical
depressive symptoms. Protocols developed for screening and interventions may
reduce FoF severity in this population.
PMID- 29956645
TI - Topography of hemispheric white matter pathology in ten cases of neuronal
intermediate filament inclusion disease.
AB - AIMS: To characterize the topography of white matter pathology in neuronal
intermediate filament inclusion disease (NIFID), a rare subtype of frontotemporal
lobar degeneration (FTLD) with "fused in sarcoma" (FUS)-immunoreactive
inclusions. MATERIAL AND METHODS: Fiber tracts from frontal and temporal lobes of
10 cases of NIFID. METHOD: Spatial patterns of the vacuolation, glial cell
nuclei, and glial inclusions (GI) were studied across cortical fiber tracts from
each case. RESULTS: Vacuoles and glial cells in NIFID were distributed either in
regularly-distributed clusters or in large diffuse clusters contrasting with
typical control cases in which smaller clusters of glial cells were surrounded by
more compact clusters of vacuoles. Axonal varicosities and GI were also observed
in the precentral gyrus (PCG) of 4 NIFID cases. Depending on region, the
densities of glial cells and vacuoles were either positively or negatively
spatially correlated, but there were no spatial correlations between the
densities of the GI and either the vacuoles or glial cells. Spatial patterns in
white matter were similar to those reported in adjacent gray matter. CONCLUSION:
1) Pathological changes across the white matter in NIFID are topographically
distributed, 2) there is a correlation between the development of vacuolation and
gliosis, and 3) white matter and gray matter pathologies are closely related.?.
PMID- 29956646
TI - HADHB mutations cause infantile-onset axonal Charcot-Marie-Tooth disease: A
report of two cases.
AB - Mitochondrial trifunctional protein deficiency (MTPD) is a rare disorder caused
by mutations in the HADHA and HADHB genes. Here, we report on two Han Chinese
patients with HADHB mutation-associated infantile axonal Charcot-Marie-Tooth
disease (IACMT). Both patients were unrelated. Case 1 was a 19-year-old man, and
case 2 was a 5-year-old boy. Both had delayed motor development and slowly
progressing distal muscle weakness with areflexia and foot deformities. The
electrophysiology findings were compatible with axonal polyneuropathy in both
patients. Blood tandem mass spectrometry showed increased concentrations of
multiple acylcarnitines. Nerve biopsies showed axonal neuropathy with a moderate
loss of myelinated fibers. Gene analysis identified two compound heterozygous
mutations (c.184A>G/c.340A>G and c.488G>A/c.1175C>T, respectively) in the HADHB
gene. The c.488G>A mutation was novel. This study broadens the phenotype of MTPD
and suggests that the genetic testing of patients suffering from IACMT should
include the HADHB gene.?.
PMID- 29956647
TI - Delayed inflammatory leukoencephalopathy after gastric bypass surgery.
AB - We describe an unusual leukoencephalopathy in a female who developed global
language and memory difficulties as well as diffuse FLAIR lesions in the cerebral
white matter (WM) ~ 30 months after bariatric surgery. She had no detectable
nutritional deficiency. She died suddenly due to cardiovascular disease. The
cerebral WM revealed perivascular T-cell infiltrations and strong
immunoreactivity for the amyloid precursor protein limited to axons, without
signs of myelin or neuronal injury. Unexplained WM lesions have been reported in
post-bariatric-surgery patients. Our findings suggest that altered immunity and
axonal dysfunction could be responsible for leukoencephalopathy in some patients
undergoing bariatric procedures.?.
PMID- 29956648
TI - A randomized, open-label, crossover study evaluating bioequivalence of two N
acetylcysteine 2% oral solution formulations in healthy subjects?.
AB - OBJECTIVE: N-acetylcysteine is a mucolytic agent used to treat bronchopulmonary
diseases associated with airway mucus hypersecretion. The bioequivalence of a new
oral N-acetylcysteine 2% formulation was evaluated relative to an appropriate
reference product. MATERIALS AND METHODS: This open-label, randomized, crossover
study assessed the bioequivalence of a new N-acetylcysteine 2% oral solution
compared to an approved reference N-acetylcysteine 2% oral solution in healthy
subjects in terms of pharmacokinetics, including area under the plasma
concentration vs. time curve of N-acetylcysteine plasma concentrations from time
0 to the last measurable sampling time point and the maximum postdose
concentration. Bioequivalence was concluded if the 90% confidence intervals for
the ratio of the geometric means of the two pharmacokinetic parameters with
baseline correction were entirely within the range of 80 - 125%. RESULTS: 46
participants were randomized. The ratios of the geometric means for the test vs.
reference treatment, with baseline correction, were 1.0961 (90% confidence
interval: 1.0228, 1.1746) for area under the plasma concentration curve of test N
acetylcysteine plasma concentrations and 1.0938 (90% confidence interval: 1.0142,
1.1796) for maximum postdose concentration; both were within the predefined range
to demonstrate bioequivalence. Most treatment-emergent adverse events were mild
or moderate and not considered study drug related. CONCLUSION: The new N
acetylcysteine 2% oral solution was found to be bioequivalent to the marketed
reference formulation. Treatments were generally safe and well tolerated.?.
PMID- 29956649
TI - Vitamin D and cinacalcet are associated with increased survival in peritoneal
dialysis but not with residual renal function preservation?.
AB - BACKGROUND: Active vitamin D and cinacalcet, a treatment for secondary
hyperparathyroidism and also with potential anti-inflammatory properties, have
been associated with lower risk of death among dialysis patients. Vitamin D has
also been described to decrease proteinuria in CKD patients. This study aims to
assess the relationship of vitamin D and cinacalcet with survival and residual
renal function preservation among peritoneal dialysis patients. MATERIALS AND
METHODS: In a retrospective peritoneal dialysis cohort of 581 subjects, we
assessed if vitamin D and cinacalcet therapy are associated with increased risk
of death and residual renal function loss using Kaplan-Meier analysis and Cox
proportional hazard analysis. RESULTS: Vitamin D treatment was associated with a
56% reduction in the risk of death (HR 0.44, 95% CI 0.28 - 0.67) and cinacalcet
also with a 54% lower risk of death (HR 0.46, 95% CI 0.31 - 0.69) in multivariate
models adjusting for each other. Hyperphosphatemia (> 6 mg/dL) was associated
with an 85% increase in mortality (HR 1.85, 95% CI 1.30 - 2.65). Neither vitamin
D (HR 1.04, 95% CI 0.45 - 2.39) nor cinacalcet (HR 0.74, 95% CI 0.45 - 1.20) were
associated with a lower risk of anuria. CONCLUSION: Vitamin D and cinacalcet
therapy was associated with a lower risk of death but not anuria, beyond other
known risk factors among peritoneal dialysis patients.?.
PMID- 29956650
TI - ?
PMID- 29956651
TI - [An history of the CRISPR-Cas systems discovery].
AB - From 1987 and during the following 20 years, a few research teams exploring
bacteria and archea genome sequences uncover the prokaryotic adaptative immune
system made of the CRISPR sequence and associated cas genes. First believed to be
similar to the eukaryote RNA interference system, CRISPR-Cas turned out to be
unique and of an amazing genetic complexity. The comparative studies of CRISPR
arrays and of cas, and later of microbiotes metagenomes allowed to propose an
evolution scenario for these systems. The results demonstrate the importance of a
naturalistic approach, without a priori, for the understanding of living
organisms.
PMID- 29956652
TI - [Why so rare if so essentiel: the determinants of the sparse distribution of
CRISPR-Cas systems in bacterial genomes].
AB - CRISPR-Cas (Cluster of Regularly Interspaced Short Palindromic Repeats) systems
confer bacteria and archaea an adaptative immunity against phages and other
invading genetic elements playing an important role in bacterial evolution.
However, despite the protection they generate and high rate of horizontal
transfer, less than 50% of bacterial genomes harbor a CRISPR-Cas system. As a
comparison, 90% of archaea encode a CRISPR-Cas system and a bacterial genome
codes for two restriction modification systems on average. This review describes
CRISPR-Cas systems distribution in bacterial genomes and then details the
different hypotheses put forward to explain the relative scarcity of CRISPR-Cas
systems. More specifically, phage escape mechanisms, ecological factors such as
phage diversity and abundance and intrinsic costs, such as maintenance or
autoimmunity, are discussed. Overall, a better understanding of the downsides of
encoding CRISPR-Cas systems is essential to explain their evolutionary dynamics
and their relative success in different environments and clades.
PMID- 29956653
TI - [CRISPR-Cas systems as weapons against pathogenic bacteria].
AB - CRISPR-Cas systems (Clustered Regularly Interspaced Short Palindromic Repeats)
are the adaptive immune system of bacteria and archaea. They target foreign
genetic elements thanks to small RNAs able to guide Cas nucleases to destroy
them. These nucleases can be reprogrammed to target chromosomal sequences rather
than invasive genetic elements. Whereas targeting the genome of eukaryotic cells
enables the efficient genesis of mutations, DNA breaks induced by Cas nucleases
are lethal in bacteria. This property can be used in the development of novel
antimicrobial strategies. CRISPR-Cas systems can be delivered to target bacteria
using bacteriophage capsids in order to specifically eliminate bacteria carrying
antibiotic resistance genes or virulence factors. These technologies enable the
development of novel tools based on CRISPR-Cas systems to specifically eliminate
pathogenic bacteria and precisely modify the composition of various microbiomes.
PMID- 29956654
TI - [High-throughput approaches to study cis-regulating elements].
AB - Gene expression in higher eukaryotes is regulated through the involvement of
transcription start site (TSS)-proximal (promoters) and -distal (enhancers)
regulatory elements. Enhancer elements play an essential role during development
and cell differentiation, while genetic alterations in these elements are a major
cause of human disease. Here, we discuss recent advances in high-throughput
approaches to identify and characterize enhancer elements, from the well
established massively parallel reporter assays to the recent clustered regularly
interspaced short palindromic repeats (CRISPR)/Cas9-based technologies. We
discuss how these approaches contribute toward a better understanding of enhancer
function in normal and pathological conditions.
PMID- 29956655
TI - ?
PMID- 29956656
TI - ?
PMID- 29956657
TI - ?
PMID- 29956658
TI - ?
PMID- 29956659
TI - ?
PMID- 29956660
TI - ?
PMID- 29956661
TI - Safety of a novel modular cage for transforaminal lumbar interbody fusion -
clinical cohort study in 20 patients with degenerative disc disease.
AB - INTRODUCTION: Transforaminal lumbar interbody fusion (TLIF) is used to
reconstruct disc height and reduce degenerative deformity in spinal fusion.
Patients with osteoporosis are at high risk of TLIF cage subsidence; possibly due
to the relatively small footprint compared to anterior interbody devices.
Recently, modular TLIF cage with an integral rail and slot system was developed
to reduce cage subsidence and allow early rehabilitation. OBJECTIVE: To study the
safety of a modular TLIF device in patients with degenerative disc disorders
(DDD) with regard to surgical complications, non-union, and subsidence. METHODS:
Patients with DDD treated with a modular TLIF cage (Polyetheretherketone (PEEK),
VTI interfuse S) were analysed retrospectively with one-year follow-up. Lumbar
sagittal parameters were collected preoperatively, postoperatively and at one
year follow-up. Cage subsidence, fusion rate, screw loosening and proportion of
endplate coverage were assessed in computed tomography scan. RESULTS: 20 patients
(age 66 +/- 10 years, 65% female, BMI 28 +/- 5 kg/m2) with a total of 37 fusion
levels were included. 15 patients had degenerative spondylosis and 5 patients had
degenerative scoliosis. The cages covered >60% of the vertebral body diameters.
Lumbar lordosis angle and segmental disc angle increased from 45.2 +/- 14.5 and
7.3 +/- 3.6 to 52.7 +/- 9.1 and 10.5 +/- 3.5 (p = 0.029 and 0.0002)
postoperatively for each parameter respectively without loss of correction at one
year follow up. One case of deep postoperative infection occurred (5%). No cage
subsidence occurred. No non-union or screw loosening occurred. CONCLUSIONS: The
modular TLIF cage was safe with regard to subsidence and union-rate. It restored
and maintained lumbar lordosis angle, segmental disc angle and disc height, which
can be attributed to the large footprint of this modular cage.
PMID- 29956662
TI - Arthroscopic excision of intra-articular sub-periosteal osteoid osteoma of elbow:
a case report.
AB - We are presenting a unique case of a sub-periosteal osteoid osteoma involving
coronoid fossa in a 25-year-old male. He was symptomatic for 2 years and his
presentation mimicked mono-articular inflammatory arthritis. His plain
radiographs were normal and the computed tomogram confirmed features of a sub
periosteal osteoid osteoma. He was treated with arthroscopic excision of the
lesion. Pain relief was noticed immediately after the surgery and maintained at
latest follow up of 1 year.
PMID- 29956663
TI - Short-term complication rate following orthopedic surgery in a tertiary care
center in Argentina.
AB - INTRODUCTION: Registration of adverse events following orthopedic surgery has a
critical role in patient safety and has received increasing attention. The
purpose of this study was to determine the prevalence and severity of
postoperative complications in the department of orthopedic unit in a tertiary
hospital. METHODS: A retrospective review from the postoperative complication
registry of a cohort of consecutive patients operated in the department of
orthopedic surgery from May 2015 to June 2016 was performed. Short-term
complications (3 months after surgery), age gender, types of surgery (elective,
scheduled urgency, non-scheduled urgency, and emergency), operative time,
surgical start time (morning, afternoon or evening), American Society of
Anesthesiologists score and surgeon's experience were assessed. Complications
were classified based on their severity according to Dindo-Clavien system: Grade
I complications do not require alterations in the postoperative course or
additional treatment; Grade II complications require pharmacological treatment;
Grade III require surgical, endoscopic, or radiological interventions without
(IIIa) or with (IIIb) general anesthesia; Grade IV are life-threatening with
single (IVa) or multi-organ (IVb) dysfunction(s), and require ICU management; and
Grade V result in death of the patient. Complications were further classified in
minor (Dindo I, II, IIIa) and major (Dindo IIIb, IVa, IVb and V), according to
clinical severity. RESULTS: 1960 surgeries were performed. The overall 90-day
complication rate was 12.7% (249/1960). Twenty-three complications (9.2 %) were
type I, 159 (63.8%) type II, 9 (3.6%) type IIIa, 42 (16.8%) type IIIb, 7 (2.8%)
type IVa and 9 (3.6%) were grade V according to Dindo-Clavien classification
(DCC). The most frequent complication was anemia that required blood transfusion
(27%) followed by wound infection (15.6%) and urinary tract infection (6%).
DISCUSSION: The overall complication rate after orthopedic surgery in our
department was 12.7%. The implementation of the DCC following orthopedic surgery
was an important tool to measure the standard of care.
PMID- 29956665
TI - Independent factors contributing to the daytime and nighttime asthmatic cough
refractory to inhaled corticosteroids.
AB - BACKGROUND: Cough is a common feature of asthma, which is often resistant to
inhaled corticosteroids (ICS). The pathophysiology involved in such
refractoriness may be different between the daytime and nighttime asthmatic
cough. We sought to identify factors contributing to the daytime and nighttime
asthmatic cough refractory to ICS treatment. METHODS: Sixty-seven patients with
asthma solely or predominantly presenting with chronic cough were prospectively
enrolled from April 2012 to December 2014. At baseline and 12 weeks after ICS
treatment, capsaicin cough threshold (C2, C5) and methacholine airway sensitivity
and reactivity were examined. Cough visual analogue scales (VAS) and numeric
scores were used to evaluate daytime and nighttime cough symptoms separately. The
Japanese version of Leicester Cough Questionnaire was also completed. When either
cough VAS or numeric scores showed an improvement of >=50% or >=2 points,
patients were considered responders to ICS treatment. RESULTS: Fifty-five
patients were eligible for evaluation. Subjective cough indices significantly
improved at 12 weeks after ICS treatment (p < 0.001). Multivariate analysis
revealed that lower C2 significantly contributed to the residual daytime cough (p
= 0.04). Meanwhile, methacholine hyperreactivity and lower IgE levels were
predictors of the nighttime residual cough (p = 0.002, and p = 0.03,
respectively). CONCLUSIONS: Heightened cough sensitivity is an independent factor
of the daytime asthmatic cough refractory to ICS. In contrast, airway reactivity
and less-allergic nature contribute to the nighttime cough refractory to ICS.
PMID- 29956666
TI - Prevalence of drugs as triggers of exacerbations in chronic urticaria.
AB - BACKGROUND AND OBJECTIVE: Many patients with chronic spontaneous urticaria (CSU)
identify different drugs as triggers of their symptoms and often make
restrictions without enough information. Objective: To estimate the clinical
impact of the drugs most frequently reported as suspects of CSU exacerbations by
patients. METHODS: All subjects were questioned about their clinical history of
urticaria and drug reactions. Drug challenge tests were performed on each patient
with the suspicious drugs. A group of healthy subjects were included as control
to evaluate the prevalence of self-reported drug reactions. RESULTS: 245 patients
with CSU and 127 healthy subjects were included. 92 (37.5%) patients and 30
(23,6%) subjects in the control group reported at least one adverse drug
reaction. Non-steroidal anti-inflammatory drugs (NSAIDs) (27.7%) and Beta-lactams
(9.4%) were the most common drugs reported by CSU group and the control group,
respectively. Positive results of challenge tests were lower than self-reports in
CSU (13%) and the control group (0.7%). CONCLUSIONS: Self-report is usually not
enough to determine a drug reaction. Drug reactions to NSAIDs and beta-lactams
are higher among patients with CSU than in subjects without urticaria. Drug
challenge tests should be offered early during medical evaluation to avoid
unnecessary restrictions.
PMID- 29956664
TI - A novel source of arterial valve cells linked to bicuspid aortic valve without
raphe in mice.
AB - Abnormalities of the arterial valve leaflets, predominantly bicuspid aortic
valve, are the commonest congenital malformations. Although many studies have
investigated the development of the arterial valves, it has been assumed that, as
with the atrioventricular valves, endocardial to mesenchymal transition (EndMT)
is the predominant mechanism. We show that arterial is distinctly different from
atrioventricular valve formation. Whilst the four septal valve leaflets are
dominated by NCC and EndMT-derived cells, the intercalated leaflets differentiate
directly from Tnnt2-Cre+/Isl1+ progenitors in the outflow wall, via a Notch-Jag
dependent mechanism. Further, when this novel group of progenitors are disrupted,
development of the intercalated leaflets is disrupted, resulting in leaflet
dysplasia and bicuspid valves without raphe, most commonly affecting the aortic
valve. This study thus overturns the dogma that heart valves are formed
principally by EndMT, identifies a new source of valve interstitial cells, and
provides a novel mechanism for causation of bicuspid aortic valves without raphe.
PMID- 29956667
TI - Exercise preconditioning attenuates atrophic mediators and preserves muscle mass
in acute sepsis.
AB - Sepsis is an inflammatory condition that causes a severe and rapid loss of body
proteins, especially skeletal muscles. The ubiquitin-proteasome system plays a
major role in skeletal muscle proteolysis. Understanding the effects of exercise
preconditioning on septic-induced ubiquitin-proteasome activation plays a pivotal
role in planning rehabilitation strategies for patients who are susceptible for
developing cachexia. In this study, we applied mild preconditioning exercises in
the form of treadmill running for adult mice for a period of two weeks, before
they were injected with lipopolysaccharide to induce sepsis. Our results show
that the body weight and cross-sectional area (CSA) of muscle fibers were
preserved in the pre-exercised mice. The main finding in our study was that pre
exercised mice maintained a low level of tumor necrosis factor-alpha in the
gastrocnemius muscle, which resulted in a down-regulated profile of main atrophic
mediators: p38, FOXO3A, and multi-ubiquitin proteins. By these findings, we
conclude that a mild program of preconditioning exercises can prevent atrophy and
preserve muscle mass in acute sepsis. This provides further evidence to the
importance of rehabilitation planning in acute illness.
PMID- 29956668
TI - H2S attenuates acute lung inflammation induced by administration of
lipopolysaccharide in adult male rats.
AB - . Hydrogen sulfide (H2S) is gasotransmitter which plays an important role in
human physiology. In this study, we aimed to check the effect of H2S treatment on
acute lung inflammation (ALI). Thirty-six adult male albino rats were used and
divided into: control group, ALI group which was intraperitoneally (i.p.)
injected with lipopolysaccharide (LPS) at a dose of 5 mg/kg body weight, ALI
group treated by the H2S donor; sodium hydrosulfide (NaHS) at a dose of 10 mg/kg
body weight i.p. and ALI group treated by i.p. injection of 80 mg/kg body weight
DL- propargylglycine (PAG) which is an inhibitor of endogenous H2S synthesis.
Serum was obtained to determine interleukin-6 (IL-6) levels. Lipid peroxides and
total antioxidant capacity (TAC) levels were measured in lung. Lung
histopathology and expression of inducible nitric oxide synthase (iNOS) were also
done. Results showed that NaHS improved lung inflammation through its inhibitory
effect on iNOS expression, decreasing the levels of IL-6 and lipid peroxides and
increasing TAC levels. But, ALI was exacerbated with PAG administration. In
conclusion, the results proved that H2S has a protective effect against LPS
induced ALI due to its anti-nitrative, anti-oxidant and anti-inflammatory
properties.
PMID- 29956669
TI - Deterministic approximation of stochastic spatially explicit model of actin
myosin interaction in discrete filament lattice.
AB - One of commonly used approaches of biophysical modeling of muscle contractile
apparatus is spatially explicit discrete lattice models in Monte Carlo
simulation. Such models allow to reproduce structural features and actin-myosin
interaction in the muscle contractile system more accurately. Limitation of such
models is their low computational efficiency and stochasticity under certain
circumstances. This work introduces deterministic approximation of stochastic
model that considers a pair of rigid contractile filaments interaction.
Approximation background is discreetness of spacing between cross-bridges and
binding sites. Due to this property cross-bridges can be divided into discrete
groups with the same strain, and considered statistically using the set of
ordinary differential equations. Deterministic model is more computationally
efficient, operates with average values. Within the given approach isotonic
contraction was simulated. A comparison with Monte Carlo simulation demonstrates
that approximation reproduces results for stochastic model with large number of
cross-bridges. Also within the deterministic model a mechanism and essential
conditions for oscillations appearance in isotonic transient response, relations
of their parameters with geometrical ones of filaments lattice were examined,
theoretical and experimental results were compared. The proposed approach can
also be applied to approximation of continuous Huxley-based models solutions.
Advantage over existing numerical methods is their greater numerical stability.
PMID- 29956670
TI - Involvement of calcium regulating ion channels in contractility of human isolated
urinary bladder.
AB - This study specified the role of several key calcium-operating ion channels in
contraction/relaxation of human detrusor muscle as possible target for overactive
bladder (OAB) treatment. Detrusor samples, obtained from 18 males (average age
61.5 +/- 5.9 years), were investigated by organ tissue bath method with following
agents: diltiazem for L-type voltage-gated calcium channels; 3-fluropyridine-4
carboxylic acid (FPCA) for Orai-STIM channels; SKF 96365-hydrochloride for
transient receptor potential (TRP) channels, T-type channels and Orai-STIM
channels; 2- aminoethoxydiphenyl borate (2-APB) for inositol-triphosphate
receptors (IP3Rs) and Orai-STIM channels. Oxybutynin and mirabegron were tested
under the same conditions as controls. Mirabegron, 2-APB and FPCA exhibited the
best suppressive effect on carbachol-induced detrusor contractility. As expressed
by area under the contractile curve (AUCC), 2-APB, FPCA and mirabegron have
similar AUCC: 1.79, 1.73, 1.73. The highest AUCC was 3.64 for diltiazem+SKF,
followed by 3.21 for diltiazem, 3.16 for SKF and 2.94 for oxybutynin. The lowest
median amplitude and contraction variability is for 2-APB followed by mirabegron
and FPCA. There were significant differences between: 2-APB/FPCA vs.: ditiazem,
diltiazem+SKF and SKF. Summary of results suggested the principal role of IP3Rs,
Orai-STIM coupling and large-conductance calcium-activated potassium channels in
detrusor contraction and pointed on Orai-STIM channels as possible targets for
OAB pharmacotherapy.
PMID- 29956671
TI - Asthma exacerbation by aspirin and chemical additives: use of a nucleotide
template model to investigate potential mechanisms.
AB - Aspirin exacerbated asthma (AEA) affects approximately 10% of the asthmatic
population. Clinical studies with a focus on abnormalities in arachidonate
metabolism do not adequately account for susceptibility. Other pharmacological
targets of aspirin receive less attention. Further investigation is required to
elucidate mechanisms, improve on diagnosis and treatment. This study employs a
molecular modeling approach, based on use of a nucleotide template, to
standardise and compare molecular structures of compounds known to induce or
prevent asthma. Results identify relative molecular similarity within the
structures of drugs and cell mediators relevant to AEA and intolerance reactions.
The investigated compounds provide equivalent fits to ligand structures for GABA,
glycine, NMDA and nicotinic receptors. Chloride and ligand-gated ion channels are
a common link between agents responsible for the induction and control of AEA.
The methodology is applicable to compounds responsible for chemical-induced
intolerance reactions..
PMID- 29956672
TI - Effect of melatonin on the behaviour of rats with continuous light-induced
hypertension.
AB - This study investigated whether continuous light exposure (CLE) results in
behavioural disturbances in rats and whether melatonin can modify these potential
changes. Four groups of 3-month-old Wistar rats were treated as follows for six
weeks: control, melatonin, CLE, and CLE with melatonin. CLE increased systolic
blood pressure and melatonin reduced it. No changes in behavioural patterns by
CLE were observed. In the controls, melatonin reduced both exploration and
locomotion but these parameters remained uninfluenced in the CLE. We conclude
that melatonin exerted a different impact on behaviour in controls and in the CLE
group.
PMID- 29956674
TI - Defect physics in complex energy materials.
AB - Understanding the physics of structurally and chemically complex transition-metal
oxide and polyanionic materials such as those used for battery electrodes is
challenging, even at the level of pristine compounds. Yet these materials are
also prone to and their properties and performance are strongly affected or even
determined by crystallographic point defects. In this review, we highlight recent
advances in the study of defects and doping in such materials using first
principles calculations. The emphasis is on describing a theoretical and
computational approach that has the ability to predict defect landscapes under
various synthesis conditions, provide guidelines for defect characterization and
defect-controlled synthesis, uncover the mechanisms for electronic and ionic
conduction and electrochemical extraction and (re-)insertion, and provide an
understanding of the effects of doping. Though applied to battery materials here,
the approach is general and applicable to any materials in which the defect
physics plays a role or drives the properties of interest. Thus, this work is
intended as an in-depth review of defect physics in particular classes of
materials, but also as a methodological template for the understanding and design
of complex functional materials.
PMID- 29956673
TI - Reshaping acetylated peptide selectivity between human BET Brd2 bromodomains BD-I
and BD-II in glioblastoma by rationally grafting secondary anchor residues.
AB - Selective inhibition of BET Brd2 BD-I and BD-II bromodomains is expected to
elicit subtle pharmacological difference in anti-glioblastoma therapy. Here,
structural basis and energetic property underlying the selective interaction of
acetylated peptide ligands with Brd2 BD-I and BD-II were investigated in detail
using molecular simulation and computational analysis. It is revealed that the
acetyl-lysine is, as expected, a primary anchor residue that confers affinity and
stability to bromodomain-peptide binding, while few secondary anchor residues
flanking the acetyl-lysine determine specificity and selectivity of peptide
interaction with different bromodomains. We also demonstrated that peptide
selectivity can be totally reversed by only grafting the secondary anchor
residues from one to another. As an instance, fluorescence-based assays showed
that the Stat3-derived acetylated peptide Stat3_K87 possesses a high affinity to
BD-II (KdBD-II = 9.7 MUM) and a strong selectivity for BD-II over BD-I (S = 0.21
fold). Grafting the three secondary anchor residues Lys8, Gly11 and Gly13 of a BD
I-over-BD-II selective H4 N-terminal peptide to the corresponding residue
positions of Stat3_K87, which results in a grafted counterpart Stat3(KGG)_K87,
can completely change the peptide selectivity from the BD-II-over-BD-I (S = 0.21
fold) of Stat3_K87 to the BD-I-over-BD-II (S = 2.5-fold) of Stat3(KGG)_K87.
PMID- 29956675
TI - STORM without enzymatic oxygen scavenging for correlative atomic force and
fluorescence superresolution microscopy.
AB - Superresolution microscopy based on localisation is usually performed in a buffer
containing enzymatic oxygen scavenger, which facilitates reversible
photoswitching of the dye molecules. This makes correlative fluorescence
localisation and atomic force microscopy (AFM) challenging, because enzymatic
oxygen scavenging interferes with the AFM cantilevers. Here we report on the
blinking kinetics of a new red cyanine dye, iFluor-647, which is similar to the
Alexa-647 dye commonly used for superresolution microscopy, but with brightness
and blinking properties which are superior to Alexa-647 in a buffer without
enzymatic oxygen scavenger. We measure the blinking behaviour of iFluor-647 in
buffers with and without enzymatic oxygen scavenger with different thiol
concentrations. We then apply this dye for correlative localisation and atomic
force microscopy in a buffer without enzymatic oxygen scavenger, which allows
acquisition of AFM and superresolution images without buffer change.
PMID- 29956676
TI - Simultaneous orthogonal plane cine imaging with balanced steady-state free
precession contrast using k-t GRAPPA.
AB - The goal of this study is to present a framework that allows cine images in
orthogonal planes to be reconstructed simultaneously using slice-interleaved
acquisitions and k-t GRAPPA. Slice-interleaved acquisitions can be interpreted as
an undersampled k-t space in which data are desired at skipped frames. Local
spatiotemporal correlations can be exploited to interpolate the skipped data to
reconstruct images in orthogonal slice groups simultaneously. An in vivo
experiment was performed in which interleaved sagittal and coronal balanced
steady-state free-precession data were acquired in the abdomens of volunteers
breathing normally. k-t GRAPPA weights were calculated from separate calibration
scans and applied to the slice-interleaved data. The images from the interpolated
frames have a similar contrast to the acquired frames, and the use of k-t GRAPPA
improved the anatomical alignment between the orthogonal images in the presence
of motion. The k-t GRAPPA reconstruction of slice-interleaved data is a promising
method for obtaining cine images of orthogonal slices simultaneously with
arbitrary contrast.
PMID- 29956677
TI - Enhanced coupling of broadband light into amorphous silicon via periodic
nanoplasmonic arrays.
AB - Achieving enhanced coupling of solar radiation over the full range of the silicon
absorption spectrum up to the bandgap is essential for increased efficiency of
solar cells, especially thin film versions. While many designs for enhancing
trapping of radiation have been explored, detailed measurements of light
scattering inside silicon cells is still lacking. Here, we demonstrate
experimentally and computationally that plasmonic-assisted localized and
traveling modes can efficiently couple red and infrared radiation into ultrathin
amorphous silicon (a-Si) layers. Utilizing patterned periodic arrays of aluminum
nanostructures on thin a-Si, we perform specular and diffuse reflectivity and
transmission measurements over a broad spectrum. Based on these results, we are
able to separate parasitic absorption in aluminum plasmonic arrays from enhanced
light absorption in the 200 nm thick amorphous silicon layer, as compared to a
blank silicon layer. We discover a very efficient near-infrared a-Si absorption
mechanism that occurs at the transition from the radiative to evanescent
diffractive coupling, analogous to earlier surface-enhanced infrared studies.
These results represent a direct demonstration of enhanced radiation coupling
into silicon due to large angle scattering and show a path forward to improved
ultrathin solar cell efficiency.
PMID- 29956678
TI - Growth kinetics of Kr nano structures encapsulated by graphene.
AB - Graphene can acquire salient properties by the intercalated nano structures, and
to functionalize the graphene as designed, understanding the growth kinetics of
the nano structures is a prerequisite. In that regards, Kr atoms are selectively
intercalated just below the surface graphene of C(0001) by the incidence of low
energy Kr ions. The growth kinetics of the encapsulated Kr nano structures is
investigated by both scanning tunneling microscopy and molecular dynamics
simulations. The intercalation proceeds via defect sites, such as surface
vacancies. At room temperature, the thermal diffusion of intercalated Kr is
almost frustrated by the strain field of the encapsulating graphene layers, and
the growth of Kr nano structures proceeds via the transient mobility of both the
intercalating Kr atoms and previously intercalated Kr atoms that are mobilized by
collision with the incident Kr ions. At the elevated temperatures where thermal
diffusion becomes effective, some Kr nano structures disappear, releasing
pressurized Kr atoms, while others coalesce to form blisters via the delamination
of the adjacent graphene. Some of the larger blisters explode to leave craters of
varying depths at the surface. In contrast to growth on the substrate, the growth
of each encapsulated nano structure depends significantly on extrinsic variables,
such as surface vacancies and local topography around the nano structure, that
affect the Kr diffusion and limit the maximal Kr pressure.
PMID- 29956679
TI - Enhanced fluorescence for in situ temperature mapping of photothermally heated
aluminum nanoparticles enabled by a plasmonic grating substrate.
AB - In situ dynamic temperature mapping of photothermally heated aluminum
nanoparticles (Al NPs) embedded in a fluoropolymer (THV) is achieved using
fluorescent dye (rhodamine 6G). A plasmonic grating substrate enhances the dye
fluorescence intensity by a factor of seven over a glass substrate, to enable
image capture rates of 500 frames per second. Further, the fluorescence intensity
is linearly related to temperature and reversible. Photothermal heating of
embedded Al NPs using a 2380 W cm-2 incident flux produced an Al NP heating rate
of 1.2 * 104 degrees C s-1. Localized Al NP motion was also observed and
attributed to thermal expansion and melting of the polymer. Multiphysics
simulation provided agreement with experimental observations, bolstering
confidence in the technique. The plasmonic grating platforms were shown to
significantly improve both fluorescence intensity and the photothermal heating of
Al compared to glass substrates, opening a new path for fast and high-resolution
in situ temperature mapping.
PMID- 29956680
TI - Localized atrophy with surrounding hair growth in a case of alopecia areata
treated with intralesional steroids, using a needle-less injector.
PMID- 29956681
TI - Novel mutations in SASH1 associated with dyschromatosis universalis hereditaria.
PMID- 29956682
TI - Evaluation of efficacy and safety of intralesional bleomycin in the treatment of
common warts: Results of a pilot study.
AB - Background: This study evaluated the efficacy and safety of intralesional
bleomycin in the treatment of common warts in 50 (32 men, 18 women) patients aged
between 14 and 80 (mean +/- SD, 28.5 +/- 13.27) years. Methods: The warts were
present over dorsal hands, feet, palms, soles and periungual skin for 1 month to
10 years. They were infiltrated with bleomycin (1 mg/ml) till blanching. The
total cumulative dose did not exceed 2 mg in one session. The treatment was
repeated after paring of eschar at 2 weeks in case there was no or partial
response. The patients were reviewed at 4, 12 and 24 weeks for cure, adverse
effects or recurrences and outcome satisfaction levels. Results: Complete cure
without recurrence occurred in 40 (80%) patients and partial response occurred in
7 (14%) patients at the end of the 24-week study period. Three patients did not
complete follow-up. No major systemic or local adverse effects other than
injection site pain for 2-3 days were noted. All cured patients were very
satisfied (Likert scale 5). Conclusion: Intralesional bleomycin appears to be an
effective and safe treatment for common warts including palmoplantar and
periungual warts. It carries the advantage of low dose, no significant adverse
effects and high patient satisfaction. Small number of patients, lack of a
control group, comparing different bleomycin concentrations and a short follow-up
are a few limitations of this study. Better designed studies are warranted for
this useful treatment modality.
PMID- 29956683
TI - Hair casts and nits - differentiating using dermoscopy.
PMID- 29956684
TI - The novel long noncoding RNA LOC283070 is involved in the transition of LNCaP
cells into androgen-independent cells via its interaction with PHB2.
AB - We sought to investigate the underlying mechanism of action of the long noncoding
RNA (lncRNA) LOC283070 in the development of androgen independence in prostate
cancer. The interactions between LOC283070 and target proteins were investigated
by RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays.
Subcellular fractionation and quantitative reverse transcription-polymerase chain
reaction (qRT-PCR) were used to detect the subcellular localization of LOC283070.
Western blotting was performed to detect the expression of prohibitin 2 (PHB2).
Luciferase activity assays were performed to evaluate the effects of LOC283070
and PHB2 on the androgen receptor (AR) signaling pathway. A methyl thiazolyl
tetrazolium (MTT) assay and a growth curve assay were used to test cell
viability. Flow cytometry was performed to analyze cell cycles. A transwell assay
was employed to test cell migration. We identified PHB2 as an interaction partner
of LOC283070 in the pull-down and RIP experiments. Furthermore, we confirmed that
the enrichment of LOC283070 with PHB2 in androgen-independent LNCaP (LNCaP-AI)
cells was much greater than that in LNCaP cells. Moreover, the expression of PHB2
was not significantly different between the two cell lines, and the expression of
LOC283070 in the nuclei of the LNCaP-AI cells was significantly greater than that
in the LNCaP cells. In vitro data revealed that PHB2 overexpression significantly
inhibited AR activity and cell proliferation and migration and induced
accumulation of prostate cancer cells in G0/G1 phase. Moreover, the
overexpression of LOC283070 fully abrogated the effects of PHB2 overexpression.
In conclusion, we found that LOC283070 can bind to PHB2 located in the nucleus
and inhibit its effect, and this is one of the mechanisms by which LOC283070 is
involved in the transition of LNCaP cells into androgen-independent cells.
PMID- 29956685
TI - Nitrosative stress in human spermatozoa causes cell death characterized by
induction of mitochondrial permeability transition-driven necrosis.
AB - Peroxynitrite is a highly reactive nitrogen species and a potent inducer of
apoptosis and necrosis in somatic cells. Peroxynitrite-induced nitrosative stress
has emerged as a major cause of impaired sperm function; however, its ability to
trigger cell death has not been described in human spermatozoa. The objective
here was to characterize biochemical and morphological features of cell death
induced by peroxynitrite-mediated nitrosative stress in human spermatozoa. For
this, spermatozoa were incubated with and without (untreated control) 3
morpholinosydnonimine (SIN-1), in order to generate peroxynitrite. Sperm
viability, mitochondrial permeability transition (MPT), externalization of
phosphatidylserine, DNA oxidation and fragmentation, caspase activation, tyrosine
nitration, and sperm ultrastructure were analyzed. The results showed that at 24
h of incubation with SIN-1, the sperm viability was significantly reduced
compared to untreated control (P < 0.001). Furthermore, the MPT was induced (P <
0.01) and increment in DNA oxidation (P < 0.01), DNA fragmentation (P < 0.01),
tyrosine nitration (P < 0.0001) and ultrastructural damage were observed when
compared to untreated control. Caspase activation was not evidenced, and although
phosphatidylserine externalization increased compared to untreated control (P <
0.001), this process was observed in <10% of the cells and the gradual loss of
viability was not characterized by an important increase in this parameter. In
conclusion, peroxynitrite-mediated nitrosative stress induces the regulated
variant of cell death known as MPT-driven necrosis in human spermatozoa. This
study provides a new insight into the pathophysiology of nitrosative stress in
human spermatozoa and opens up a new focus for developing specific therapeutic
strategies to better preserve sperm viability or to avoid cell death.
PMID- 29956686
TI - Risk of prostate cancer in men with spinal cord injury: A systematic review and
meta-analysis.
AB - A lower risk of prostate cancer has been reported in men with spinal cord injury
(SCI) as compared to that observed in able-bodied subjects. As injury-related
consequences can have opposite effects on prostate pathophysiology, this meta
analysis aimed to (1) establish the existence/quantify the extent of decreased
prostate cancer risk following SCI and (2) find out if there is any statistically
significant difference in prostate-specific antigen (PSA) levels between SCI and
able-bodied subjects. MEDLINE, Cochrane Library, Scopus, CINAHL, and
ScienceDirect databases were used. Only studies reporting a prostate cancer
diagnosis and/or PSA levels following SCI and in able-bodied controls were
included. Five studies provided information about prostate cancer on 35 293
subjects with SCI and 158 140 controls. Six studies were included in PSA analysis
which reported information on 391 men with SCI and 1921 controls. Pooled
estimates indicated that SCI reduced the prostate cancer risk by approximately
50% as compared to controls, whereas differences in PSA levels were not
statistically significant. Funnel plots suggested the presence of publication
bias only in PSA analysis. Between-study heterogeneity was established and when,
according to meta-regression models, analysis was restricted to studies including
men with mean age over 55 years, prostate cancer risk in SCI decreased up to
65.0% than that in controls with no heterogeneity (P = 0.33, I2 = 9%). In
conclusion, in men over 55 years old, SCI decreases the prostate cancer risk up
to 65.0% than that in controls. The large between-study heterogeneity on PSA
confirms its poor reliability as a screening tool for prostate cancer in SCI.
PMID- 29956687
TI - Unpaired sex chromosomes in metaphase I human spermatocytes locally modify
autosomal bivalents positioning.
PMID- 29956688
TI - Nonalcoholic fatty liver disease burden - Saudi Arabia and United Arab Emirates,
2017-2030.
AB - Background/Aim: Due to epidemic levels of obesity and type 2 diabetes mellitus
(DM), nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic
steatohepatitis (NASH) will be driving factors in liver disease burden in the
coming years in Saudi Arabia and United Arab Emirates (UAE). Materials and
Methods: Models were used to estimate NAFLD and NASH disease progression,
primarily based on changes in adult prevalence rates of adult obesity and DM. The
published estimates and expert interviews were used to build and validate the
model projections. Results: In both countries, the prevalence of NAFLD increased
through 2030 parallel to projected increases in the prevalence of obesity and DM.
By 2030, there were an estimated 12,534,000 NAFLD cases in Saudi Arabia and
372,000 cases in UAE. Increases in NASH cases were relatively greater than the
NAFLD cases due to aging of the population and disease progression. Likewise,
prevalent cases of compensated cirrhosis and advanced liver disease are projected
to at least double by 2030, while annual incident liver deaths increase in both
countries to 4800 deaths in Saudi Arabia and 140 deaths in UAE. Conclusions:
Continued high rates of adult obesity and DM, in combination with aging
populations, suggest that advanced liver disease and mortality attributable to
NAFLD/NASH will increase across both countries. Reducing the growth of the NAFLD
population, along with potential therapeutic options, will be needed to reduce
liver disease burden.
PMID- 29956689
TI - Association of coagulopathy with the risk of bleeding after invasive procedures
in liver cirrhosis.
AB - Background/Aim: Bleeding risk among patients with acute or chronic liver disease
after invasive procedures is a common concern in clinical practice. This
retrospective study aimed to explore whether the presence of coagulopathy
increased the risk of major bleeding after invasive procedures in cirrhosis.
Patients and Methods: A total of 874 cirrhotic patients underwent invasive
procedures. Coagulopathy was defined as international normalized ratio (INR)
>=1.5 and/or platelets (PLTs) <=50 * 109/L. Severe thrombocytopenia was defined
as PLTs <= 50 * 109/L. Invasive procedures, major bleeding after invasive
procedures, and in-hospital deaths were recorded. Results: In all, 296 patients
(33.9%) had coagulopathy. Major bleeding after invasive procedures occurred in 21
patients (2.4%). Major bleeding after invasive procedures was more frequent in
patients with coagulopathy than those without coagulopathy (4.1% vs 1.6%, P =
0.023). Major bleeding after invasive procedures was more frequent in patients
with severe thrombocytopenia than those without severe thrombocytopenia (4.9% vs
1.6%, P = 0.008). Incidence of major bleeding after invasive procedures was not
significantly different between patients with INR >= 1.5 and INR < 1.5 (4.5% vs
2.0%, P = 0.065). Patients with INR >=1.5 had a significantly higher in-hospital
mortality than those with INR < 1.5 (6.4% vs 1.3%, P < 0.001). Conclusion: Severe
thrombocytopenia significantly increased the risk of major bleeding after
invasive procedures in cirrhosis. INR >= 1.5 significantly increased in-hospital
mortality.
PMID- 29956690
TI - Genetic susceptibility for celiac disease is highly prevalent in the Saudi
population.
AB - Background/Aim: To determine the frequency of celiac disease (CD)-predisposing
human leukocyte antigen (HLA)-DQ genotypes in the Saudi population, where the
prevalence of CD is 1.5% as recently reported in a mass screening study. Patients
and Methods: In a cross-sectional population-based study, a total of 192 randomly
selected healthy school children (97 females, mean age 10.5 +/- 2.2 years, all
negative for tissue transglutaminase-IgA) were typed for D QA1 and D QB1 genes by
polymerase chain reaction sequence-specific oligonucleotide probes. Results: Of
the 192 children, 52.7% carried the high-risk CD-associated HLA-DQ molecules:
homozygous DQ2.5 ( 2.6%), DQ2.5/DQ2.2 ( 4.7%), heterozygous DQ2.5 ( 28.15%),
homozygous DQ8 ( 4.2%), DQ8/DQ2.2 ( 3.6%), and double dose DQ2.2 ( 9.4%). Low
risk CD-associated HLA-DQ molecules (single dose DQ2.2 and heterozygous DQ8)
constituted 3.6% and 9.4%, respectively. Among the very low-risk groups,
individuals lacking alleles that contribute to DQ2/DQ8 variants (33.5%), 13.5%
carried only one of the alleles of the high-risk HLA-DQ2.5 heterodimer called
"half-heterodimer" (HLA-DQA1*05 in 12% and HLA-DQB1* 02 in 1.5%), and 20.8%
lacked all the susceptible alleles (DQX.x). Gender distribution was not
significantly different among the CD-risk groups. Conclusion: We report one of
the highest frequencies of CD-predisposing HLA-DQ genotypes among healthy general
populations (52.7%) worldwide, which might partly explain the high prevalence of
CD in the Saudi community.
PMID- 29956691
TI - Trends in Mortality and Morbidity in Infants Under 500 Grams Birthweight:
Observations from Our Neonatal Intensive Care Unit (NICU).
AB - BACKGROUND In our previous study, some changes were presented in obstetric care
and we studied the morbidity and mortality trends of infants with <500 grams
birth weight. Several neonatal protocol changes occurred during the study period.
The aim of this study was to analyze the changes in mortality and morbidity of
premature infants in light of changing neonatal protocols. MATERIAL AND METHODS
We performed a retrospective study of premature infants with <500 grams birth
weight, born at our department between 2006 and 2015. We divided the study period
into two 5-year epochs and compared mortality and morbidity rates. We calculated
the duration of mechanical ventilation and non-invasive respiratory support, and
also investigated the potential impact of the differences in clinical practice.
RESULTS The survival rate was 30.8% during first epoch, which was significantly
lower than the 70.4% survival rate during second epoch. There was no difference
in the rate of complications between the 2 epochs. The total number of ventilator
and non-invasive ventilation days was significantly lower in the second epoch.
CONCLUSIONS We found significant differences in survival rates but no change in
the incidence of morbidities between the 2 epochs. Therefore, although the number
of neonates surviving with morbidities has increased, so did the number of those
with intact survival. The increased survival of infants born with <500 grams
birth weight is not associated with increased rate of morbidities. Protocol
changes may have contributed to these findings; however, in a retrospective study
it is not possible to separate the impact of individual changes.
PMID- 29956692
TI - [Cultural differences in the food preferences of school population].
AB - OBJECTIVE: The combination of cultures can affect the feeding of the native
population and immigrant, influencing the school population. The objective of
this study was to analyze the habits and eating habits of schoolchildren and the
relationships with their cultural environment. METHODS: A cross-sectional
descriptive study of a representative sample of 325 parents and students of
primary school of an Almeria population was conducted. For the analysis of the
qualitative variables Chi square was applied and for the quantitative ones, U of
Mann-Whitney and Kruskal-Wallis was applied. RESULTS: The results showed a higher
preference for vegetables in girls (42.22%) than in boys (30.34%). In
schoolchildren who did not go to the school canteen, vegetable consumption was
higher (pieces of vegetable Me=2,15), preference for dairy products 94.4% and
fish 89.8%. Although 45.6% of children, whose parents came from North Africa,
reported not having tasted pork, 29.4% were satisfied with this type of food. We
observed a higher consumption of fruits and vegetables in children whose parents
came from North Africa (pieces of fruit Me=3,42 and pieces of vegetable Me=2,38,
respectively). CONCLUSIONS: Through this study we observed a higher consumption
of vegetables and higher preferences for dairy and fish in schoolchildren who did
not go to the school canteen. Likewise, it was possible to observe an incipient
change in the food patterns of the population from North Africa influenced by
culture of the native population, referring to the consumption of pork. In
general, the results showed a greater variety of consumption, in the children of
foreign parents.
PMID- 29956693
TI - Revealing the spatial distribution of chemical species within latent fingermarks
using vibrational spectroscopy.
AB - Latent fingermarks are an important form of crime-scene trace evidence and their
usefulness may be increased by a greater understanding of the effect of chemical
distribution within fingermarks on the sensitivity and robustness of fingermark
detection methods. Specifically, the relative abundance and micro-distribution of
sebaceous (lipophilic) and eccrine (hydrophilic) material in fingermarks have
long been debated in the field, yet direct visualisation of relative abundance
and micro-distribution was rarely achieved. Such a visualisation is nonetheless
essential to provide explanations for the variation in reproducibility or
robustness of latent fingermark detection with existing methods, and to identify
new strategies to increase detection capabilities. In this investigation, we have
used SR-ATR-FTIR and confocal Raman microscopy to probe the spatial micro
distribution of the sebaceous and eccrine chemical components within latent
fingermarks, deposited on non-porous surfaces. It was determined that fingermarks
exhibit a complex spatial distribution, influenced by the ratio of lipophilic to
aqueous components, and to a first approximation resemble a water-in-oil or oil
in-water emulsion. Detection of a substantial lipid component in "eccrine
enriched fingermarks" (wherein hands are washed to remove lipids) is noteworthy,
as it provides a potential explanation for several scenarios of unexpected
fingermark detection using methods previously thought unsuitable for "eccrine
deposits". Furthermore, the pronounced distribution of lipids observed in natural
fingermark deposits was intriguing and agrees with recent discussion in this
research field that natural fingermarks contain a much higher lipid content than
previously thought.
PMID- 29956694
TI - Selective radiolabelling with 68Ga under mild conditions: a route towards a
porphyrin PET/PDT theranostic agent.
AB - A theranostic conjugate for use as a positron emission tomography (PET)
radiotracer and as a photosensitiser for photodynamic therapy (PDT) has been
synthesised. A water-soluble porphyrin was coupled with the bifunctional chelate,
H4Dpaa.ga. This conjugate is capable of rapid 68Ga complexation under
physiological conditions; with 93% and 80% radiochemical yields achieved, at pH
4.5 and pH 7.4 respectively, in 15 min at 25 degrees C. Photocytotoxicity was
evaluated on HT-29 cells and showed the conjugate was capable of >50% cell death
at 50 MUM upon irradiation with light, while causing minimal toxicity in the
absence of light (>95% cell survival).
PMID- 29956695
TI - Orthogonal reactivity of Ni(i)/Pd(0) dual catalysts for Ullmann C-C cross
coupling: theoretical insight.
AB - Dual catalysis has become a desirable alternative because of the synergetic
effect of two distinct catalysts, but little is known about the mechanism of dual
catalysis and its effect on the high reactivity and selectivity. Here, a novel
Ullmann C-C cross-coupling of bromobenzene and 4-methoxyphenyltriflate via
nickel/palladium dual catalysis has been investigated using density functional
theory. The orthogonal reactivity of NiI/Pd0 combination is the precondition and
foundation of achieving such a Ullmann cross-coupling reaction. In the present
dual catalysis, the NiI complex acts as the primary catalyst, while the Pd0
catalyst plays a decisive role in the cross-selectivity.
PMID- 29956696
TI - Prediction and understanding of AIE effect by quantum mechanics-aided machine
learning algorithm.
AB - Significant effort has been devoted to the research of aggregation-induced
emission (AIE); however, the discovery of new AIE materials is driven mainly by
laborious trial-and-error. In this study, taking triphenylamine (TPA)-based
luminophores as an example, we propose an efficient machine-learning scheme for
predicting AIE-activity based on quantum mechanics.
PMID- 29956697
TI - On the possibility of an Eley-Rideal mechanism for ammonia synthesis on Mn6N5+x
(x = 1)-(111) surfaces.
AB - Recently we reported an Eley-Rideal/Mars-van Krevelen mechanism for ammonia
synthesis on cobalt molybdenum nitride (Co3Mo3N). In this mechanism hydrogenation
of activated dinitrogen occurs directly from the gas phase in a low barrier step
forming a hydrazinylidene intermediate [double bond, length as m-dash]NNH2. In
this paper we study whether such a mechanism of ammonia synthesis could occur on
the (111) surface of another metal nitride, Mn6N5+x (x = 1), as this would
explain the low-T ammonia synthesis activity of Co3Mo3N. We find that although N2
adsorbs more strongly than H2 on the (111) surface, having also examined the
(110) and the (100) surface, N2 is not significantly activated when adsorbed in
an end-on configuration. The hydrogenation reactions via an Eley-Rideal mechanism
are all high barrier processes (>182 kJ mol-1) and therefore an Eley-Rideal
mechanism for ammonia synthesis is predicted to not occur on this material unless
there are high temperatures. Our study indicates that the fact that an Eley
Rideal/Mars-van Krevelen mechanism occurs on Co3Mo3N is a result of the stronger
activation of dinitrogen at nitrogen vacancies when dinitrogen is adsorbed in an
end-on configuration.
PMID- 29956698
TI - Understanding the non-covalent interaction mediated modulations on the electronic
structure of quasi-zero-dimensional graphene nanoflakes.
AB - In recent years, magnetic or electric field induced modulations on the electronic
environment of single molecular systems are common practice. In this particular
study, we have instigated the possibility of controlling the electronic and spin
dependent properties of hydrogen-terminated graphene fragments, so-called
graphene nanoflakes (GNF), using weak non-covalent interactions as the external
stimuli. The topological frustration in the graphene fragment appreciated the
compelling electronic behavior of the system. This leads to some unorthodox spin
distribution in the system and it is possible to synchronize this electronic
perturbation switching through a non-covalent interaction. These findings
institute a new avenue for sculpting such donor-acceptor composites as self
regulated spintronic devices in next generation electronics.
PMID- 29956699
TI - An interdigitated electrode with dense carbon nanotube forests on conductive
supports for electrochemical biosensors.
AB - A highly sensitive interdigitated electrode (IDE) with vertically aligned dense
carbon nanotube forests directly grown on conductive supports was demonstrated by
combining UV lithography and a low temperature chemical vapor deposition process
(470 degrees C). The cyclic voltammetry (CV) measurements of K4[Fe(CN)6] showed
that the redox current of the IDE with CNT forests (CNTF-IDE) reached the steady
state much more quickly compared to that of conventional gold IDE (Au-IDE). The
performance of the CNTF-IDE largely depended on the geometry of the electrodes
(e.g. width and gap). With the optimum three-dimensional electrode structure, the
anodic current was amplified by a factor of ~18 and ~67 in the CV and the
chronoamperometry measurements, respectively. The collection efficiency, defined
as the ratio of the cathodic current to the anodic current at steady state, was
improved up to 97.3%. The selective detection of dopamine (DA) under the
coexistence of l-ascorbic acid with high concentration (100 MUM) was achieved
with a linear range of 100 nM-100 MUM, a sensitivity of 14.3 mA mol-1 L, and a
limit of detection (LOD, S/N = 3) of 42 nM. Compared to the conventional carbon
electrodes, the CNTF-IDE showed superior anti-fouling property, which is of
significant importance for practical applications, with a negligible shift of the
half-wave potential (DeltaE1/2 < 1.4 mV) for repeated CV measurements of DA at
high concentration (100 MUM).
PMID- 29956700
TI - Phase stability, electronic structures and elastic properties of (U,Np)O2 and
(Th,Np)O2 mixed oxides.
AB - Mixing enthalpies (DeltaHmix) of U1-xNpxO2 and Th1-xNpxO2 solid solutions are
derived from atomic scale simulations based on density functional theory (DFT)
employing the generalised gradient approximation corrected with an effective
Hubbard parameter (Ueff). The variation of structural and electronic properties
of UO2 and NpO2 with collinear ferromagnetic (FM), collinear anti-ferromagnetic
(AFM) and non-collinear anti-ferromagnetic arrangements of the uranium and
neptunium magnetic moments are investigated while ramping up Ueff from 0 eV to 4
eV (the Ueff-ramping method). A combination of the Ueff-ramping method to treat
the presence of metastable magnetic states and special-quasirandom structures
(SQS) for the random distribution of Np atoms in UO2 and ThO2 is employed to
calculate DeltaHmix of U1-xNpxO2 and Th1-xNpxO2 mixed oxides (MOX). The effect of
collinear FM and AFM ordering is also considered in determining the DeltaHmix.
The calculated DeltaHmix of Th1-xNpxO2 MOX were positive compared to the end
members and nearly symmetric around x = 0.5 and DeltaHmix of the AFM
configuration were higher compared to the FM configuration maximum by 0.19 kJ mol
1. The DeltaHmix of U1-xNpxO2 MOX were negative up to U0.50Np0.50O2 with a
maximum value of -1.21 kJ mol-1 for U0.4375Np0.5625O2 whereas Np-rich (U,Np)O2
MOX compositions exhibited DeltaHmix close to zero. Values of DeltaHmix for
(Th,Np)O2 are consistent with a simple miscibility-gap phase diagram while those
for (U,Np)O2 suggest more complex behaviour. Nevertheless, lattice parameter
variation with composition still follows a Vegard's law relationship. Finally,
single crystal elastic constants of pure oxides and MOX are reported. The linear
elasticity models describe the mixing energies to within an accuracy of
approximately 1 kJ mol-1 for the U1-xNpxO2 and Th1-xNpxO2 MOX systems.
PMID- 29956701
TI - A viable strategy for screening the effects of glycan heterogeneity on target
organ adhesion and biodistribution in live mice.
AB - This work represents the first broad study of testing diverse heterogenous
glycoconjugates (7 different glycoalbumins) for their differential in vivo
binding (11 different cancer cell types) in both cell- and animal-based studies.
As a result, various changes in biodistribution, excretion, and even tumor
adhesion were observed.
PMID- 29956702
TI - Loss of water from protonated polyglycines: interconversion and dissociation of
the product imidazolone ions.
AB - Collision-induced dissociation of isotopically labelled protonated pentaglycine
produced two abundant [b5]+ ions, the products of the loss of water from the
first and second amide groups, labelled [b5]+I and [b5]+II. IRMPD spectroscopy
and DFT calculations show that these two [b5]+ ions feature N1-protonated 3,5
dihydro-4H-imidazol-4-one structures. 15N-Labelling established that some
interconversion occurs between these two ions but dissociations are preferred.
For both ions, DFT calculations show that the barrier to interconversion is
slightly higher than those to dissociation. Dehydration of protonated hexaglycine
produced three imidazolone ions. Ions [b6]+I and [b6]+II exhibit analogous CID
spectra to those from [b5]+I and [b5]+II; however, the spectrum of the [b6]+III
ion was dramatically different, showing losses predominantly of a further water
molecule or cleavage of the second amide bond to give the glycyloxazolone (a
deprotonated [b2]+ ion, labelled GlyGlyox (114 Da)) from the N-terminus.
Protonated polyglycines [Glyn + H]+, where n = 7-9, all readily lose at least one
water molecule. The corresponding [bn]+ ions lose either a further water
molecule, an oxazolone from the N-terminus or a truncated peptide from the C
terminus. The number of amino acid residues in the latter two eliminated neutral
molecules provides insight into the location of the imidazolone in the peptide
chain and which oxygen was lost in the initial dehydration reaction. From this
analysis, it appears that water loss from the longer protonated polyglycines is
predominantly from the central residues.
PMID- 29956703
TI - Detection of exogenous substances in latent fingermarks by silver-assisted LDI
imaging MS: perspectives in forensic sciences.
AB - For over one hundred years, the fingerprint has reigned as one of the most
trusted pieces of forensic evidence for suspect identification. In the last few
decades, the modernization of chemical analysis technologies led scientists to
explore new possibilities to further analyse fingermarks sampled from a crime
scene. Indeed, the detection of chemicals a suspect has been in contact with
before or during the crime can provide valuable insights into criminal
investigations. In this regard, imaging mass spectrometry (IMS) has shown to be a
powerful tool for the analysis of fingermarks by combining suspect identification
and the detection of numerous endogenous and exogenous compounds. A novel
approach developed in our laboratory, silver-assisted laser desorption ionization
(AgLDI), was adopted to allow for the chemical analysis of latent fingermarks
left on nonconductive surfaces (such as paper, cardboard, plastic and forensic
lifting tape) with a time-of-flight mass spectrometer. In this study, we continue
to evaluate the potential of AgLDI IMS to provide circumstantial evidence by
detecting exogenous substances. We first demonstrate that owner-specific chemical
signatures can be recovered from fingermarks based on the presence of several
cosmetics and personal care products. We then show the possibility of detecting
and imaging fingermarks containing three common illicit drugs, namely
tetrahydrocannabinol, cocaine and heroin. Finally, we demonstrate that the
methodology also allows us to successfully image bloody fingermarks after
appropriate forensic enhancement treatments. Overall, we believe that AgLDI IMS
has significant potential that could positively contribute to forensic
investigations.
PMID- 29956704
TI - Cu(ii)-tBu-PHOX catalyzed enantioselective malonate addition onto 3-hydroxy 2
oxindoles: application in the synthesis of dimeric pyrroloindoline alkaloids.
AB - An efficient Cu(ii)-PHOX-catalyzed malonate addition onto 3-hydroxy 3-indolyl-2
oxindoles is envisioned to afford excellent enantioselectivities (up to >99% ee)
in high chemical yields. Detailed characterization techniques including X-ray,
NMR, CV and EPR experiments suggest that a Cu(ii)-complex is involved as an
active species in this process. Applying this strategy, an advanced intermediate
of cyclotryptamine alkaloids has been synthesized in few steps for a general
approach to bis-cyclotryptamine alkaloids.
PMID- 29956705
TI - Reviving lithium cobalt oxide-based lithium secondary batteries-toward a higher
energy density.
AB - By breaking through the energy density limits step-by-step, the use of lithium
cobalt oxide-based Li-ion batteries (LCO-based LIBs) has led to the unprecedented
success of consumer electronics over the past 27 years. Recently, strong demands
for the quick renewal of the properties of electronic products every so often
have resulted in smarter, larger screened, more lightweight devices with longer
standby times that have pushed the energy density of LCO-based LIBs nearly to
their limit. As a result, with the aim of achieving a higher energy density and
lifting the upper cut-off voltage of LCO above 4.45 V (vs. Li/Li+), the
development of LCO-based all-solid-state lithium batteries (ASSLBs) with a Li
metal anode and LCO-based full cells with high-performance anodes have become
urgent scientific and technological requirements. This review summarizes the key
challenges of synthesizing LCO-based LBs with a higher energy density from the
perspectives of structure and interface stability, and gives an account of
effective modification strategies in view of the electrodes, liquid electrolytes,
binders, separators, solid electrolytes and LCO-based full cells. The improvement
mechanisms of these modification strategies and the controversy over them are
also analyzed critically. Moreover, some perspectives regarding the remaining
challenges for LCO-based LBs towards a higher energy density and possible future
research focuses are also presented.
PMID- 29956706
TI - Stimulating intra- and intermolecular charge transfer and nonlinear optical
response for biphenalenyl biradicaloid dimer under an external electric field.
AB - An interesting biphenalenyl biradicaloid (IDPL) dimer consisting of both-middle
superimposed phenalenyls and both-end nonsuperimposed phenalenyls has been
synthesized, and has attracted intensive research interest due to its intra- and
intermolecular interactions and semiconductive characteristics. It is significant
that under regulation of the external electric field the directional charge
transfer (CT) can produce attractive properties. In the present work, the
structure and electronic properties of the IDPL dimer under an external electric
field (along the horizontal Fx or the vertical Fz directions) are explored, and
the following properties determined: (i) as the horizontal Fx increases, the
intramolecular CT becomes larger, which induces the intermolecular CT of the IDPL
dimer. (ii) In contrast, as the vertical Fz increases, the large intermolecular
CT gives rise to the intramolecular CT of the IDPL dimer. (iii) More importantly,
the external electric field effectively regulates and controls the first
hyperpolarizability (betatot) of the IDPL dimer. Compared with the vertical Fz,
the horizontal Fx induces a larger first hyperpolarizability (betatot = 5.48 *
105 a.u.). Furthermore, the application of a uniform external electric field
(Fx,y,z) to the IDPL dimer was investigated to define the external electric field
direction of the material application. The betatot values were increased with
increasing of the uniform Fx,y,z. Our study provides an effective strategy for
developing high-performance NLO materials by tuning the external electric field,
and could be of significance for application in switch devices.
PMID- 29956707
TI - Lasso peptides: chemical approaches and structural elucidation.
AB - The discovery and development of novel constrained peptides that combine the
advantages of therapeutic proteins with those of small molecules has partially
prompted the re-emergence of peptides as therapeutics. In this regard, lasso
peptides are characterized by both the selectivity and potency of larger protein
biologics but with no or low immunogenicity, and the stability and
bioavailability of small molecules. Moreover, the diverse functionality of lasso
peptides and their extraordinary stability against chemical, thermal and
proteolytic degradation make them attractive candidates for drug discovery.
However, the chemical synthesis of lasso peptides remains a challenge due to the
difficulty in building and maintaining their threaded structure. From a
therapeutic point of view, these small and constrained structures would provide a
new paradigm in drug discovery.
PMID- 29956708
TI - Palladium-catalyzed selective synthesis of 3,4-dihydroquinazolines from electron
rich arylamines, electron-poor arylamines and glyoxalates.
AB - A simple palladium-catalyzed selective synthesis of structurally diverse 3,4
dihydroquinazolines from electron-rich arylamines, electron-poor arylamines and
glyoxalates has been developed under mild conditions. This reaction is carried
out in a tandem manner constituted by the condensation of arylamines and
glyoxalates, the selective Diels-Alder cycloaddition and oxidation processes, in
which 4-nitrothiophenol was used as the key ligand.
PMID- 29956709
TI - Crystalline, room-temperature stable phosphine-SO2 adducts: generation of sulfur
monoxide from sulfur dioxide.
AB - The particularly basic phosphines 1a-c readily form isolable, zwitterionic Lewis
base adducts with SO2 that were fully characterized including by X-ray
diffraction studies. Computational and reactivity studies show that these adducts
readily release SO at room temperature driven by the formation of the
corresponding phosphine oxides.
PMID- 29956710
TI - Confinement of H2O and EtOH to enhance CO2 capture in MIL-53(Al)-TDC.
AB - EtOH sorption properties were investigated in MIL-53(Al)-TDC and found a strong
interaction between EtOH and the MOF material (DeltaHads = 69.6 kJ mol-1). CO2
capture was enhanced upon confining small amounts of H2O. Upon confining small
amounts of EtOH however, the CO2 uptake was not improved. The difference in CO2
uptake with EtOH and H2O was rationalised using computational calculations. The
analysis of the quantum theory of atoms in molecules (QTAIM) showed a covalent
interaction between a MOF model and confined molecules (EtOH and H2O), and no
difference in the hydrogen bonds between confined molecules and CO2.
PMID- 29956711
TI - Thymus pulegioides L. as a rich source of antioxidant, anti-proliferative and
neuroprotective phenolic compounds.
AB - The potential of Thymus pulegioides L. as an alternative and valuable source of
functional ingredients has been assessed. For this purpose, the phenolic
constituent profiles and the antioxidant, anti-proliferative, neuroprotective,
anti-aging and anti-diabetic activities of both T. pulegioides aqueous decoctions
(AD) and hydro-ethanolic extracts (HE) were studied and compared for the first
time. Rosmarinic acid was the main phenolic compound, accounting for 35.2% or
47.8% of total identified phenols in AD or HE, respectively (58.5 and 151.9 mg g
1 extract). Furthermore, large amounts of luteolin-O-hexuronide (AD: 39.9 +/- 2.5
mg g-1, HE: 60.8 +/- 7.0 mg g-1), eriodictyol-O-hexuronide (AD: 19.9 +/- 2.5 mg g
1, HE: 26.8 +/- 7.0 mg g-1) and chrysoeriol hexoside (AD: 23.5 +/- 0.7 mg g-1,
HE: 16.0 +/- 0.7 mg g-1) were found. Both extracts showed significant in vitro
antioxidant activity and anti-proliferative activity against Caco-2 cells (IC50
82.25 MUg mL-1 and 105.44 MUg mL-1, AD and HE, respectively), and reduced
hepatotoxicity (HepG2 cells). In general, both T. pulegioides extracts showed
poor anti-diabetic activity, moderate anti-aging effects and high neuroprotective
activity with both AD and HE extracts, at 0.5 mg mL-1, showing 80% inhibition of
the acetylcholinesterase activity and 94% inhibition of the tyrosinase activity.
The present study highlights the important potential of this herb as a functional
food ingredient.
PMID- 29956713
TI - Strain-specific properties of Lactobacillus plantarum for prevention of
Salmonella infection.
AB - Salmonella is a common food-borne pathogen; since lactobacilli show great
potential for protecting against Salmonella infections, they are used as dietary
supplements in functional foods. The aim of this study is to investigate the
strain-specific properties and the involved mechanisms of action of Lactobacillus
plantarum towards prevention of Salmonella infection. Mice were pretreated with
mixed strains or single strain of Lactobacillus plantarum for 10 d prior to
infection with Salmonella typhimurium SL1344, and the survival rates showed that
lactobacilli exhibited strain-specific properties for preventing Salmonella
infection. Then, in vitro and in vivo studies were carried out to investigate the
involved mechanism of the strain-specific properties. The results showed that
different Lactobacillus plantarum strains had different effects on inhibiting
Salmonella growth, thus preventing adhesion to and invasion of epithelial cells
by pathogens and enhancing immune responses. The present study demonstrated
strain-specific properties of probiotics to prevent Salmonella infection and
elucidated their underlying mechanisms.
PMID- 29956712
TI - A synthetic biological quantum optical system.
AB - In strong plasmon-exciton coupling, a surface plasmon mode is coupled to an array
of localized emitters to yield new hybrid light-matter states (plexcitons), whose
properties may in principle be controlled via modification of the arrangement of
emitters. We show that plasmon modes are strongly coupled to synthetic light
harvesting maquette proteins, and that the coupling can be controlled via
alteration of the protein structure. For maquettes with a single chlorin binding
site, the exciton energy (2.06 +/- 0.07 eV) is close to the expected energy of
the Qy transition. However, for maquettes containing two chlorin binding sites
that are collinear in the field direction, an exciton energy of 2.20 +/- 0.01 eV
is obtained, intermediate between the energies of the Qx and Qy transitions of
the chlorin. This observation is attributed to strong coupling of the LSPR to an
H-dimer state not observed under weak coupling.
PMID- 29956714
TI - Secondary Cutaneous Epstein-Barr Virus-associated Diffuse Large B-cell Lymphoma
with Hodgkin/Reed-Sternberg-like Cells in a Patient with Angioimmunoblastic T
cell Lymphoma.
PMID- 29956715
TI - Eccrine Porocarcinoma of the Skin is Rising in Incidence in the East of England.
PMID- 29956716
TI - Effects of Film Dressings on Itch Hypersensitivity Using Murine Dry Skin Models.
PMID- 29956717
TI - Chlamydiales Bacterial Sequences in Lesional and Healthy Skin of Patients with
Parapsoriasis.
PMID- 29956718
TI - A Case of Ankyloblepharon-ectodermal Defects-cleft Lip/palate-syndrome with
Choanal Atresia and Skin Erosions: Phenotypic Variability of TP63-related
Disorders.
PMID- 29956719
TI - Exposure to EGF and 17beta-estradiol irreversibly affects the proliferation and
transformation of MCF7 cells but is not sufficient to promote tumor growth in a
xenograft mouse model upon withdrawal of exposure.
AB - Epidermal growth factor (EGF) and estrogen are potent regulators of breast
tumorigenesis. Their short-term actions on human breast epithelial cells have
been investigated extensively. However, the consequence of a long-term exposure
to EGF and estrogen remains to be fully elucidated. The present study examined
the effects of long-term exposure to EGF and 17beta-estradiol on the
proliferation, transformation, expression of markers of stemness, and
tumorigenesis of MCF7 human breast adenocarcinoma cells. Exposure to EGF and/or
17beta-estradiol irreversibly enhanced the proliferation rate of MCF7 cells, even
following withdrawal. However, in a mouse xenograft experiment, no significant
difference in tumor volume was observed between tumors derived from cells exposed
to EGF, 17beta-estradiol or EGF + 17beta-estradiol. Immunohistochemistry
performed on tumors derived from 17beta-estradiol-exposed cells revealed reduced
cell proliferation and vessel scores, according to the results obtained using
Ki67 and von Willebrand factor staining, respectively. The EGF- and/or 17beta
estradiol-treated cells exhibited an increased ratio of cluster of
differentiation (CD)44+/CD24- cells and enhanced ability to form mammospheres.
Furthermore, the long-term exposure of MCF7 cells to EGF and 17beta-estradiol
altered their responsiveness to short-term stimulatory or inhibitory treatments
with EGF, 17beta-estradiol, transforming growth factor-beta1 (TGFbeta1), Iressa
and SB431542. Therefore, the findings indicated that sustained exposure of MCF7
cells to EGF and/or 17beta-estradiol resulted in enhanced cell proliferation and
mammosphere formation, an increased ratio of CD44+/CD24- cells, and altered
responses to short-term treatments with EGF, 17beta-estradiol, TGFbeta1, and
drugs inhibiting these signaling pathways. However, this sustained exposure was
not sufficient to affect tumor take or volume in a xenograft mouse model.
PMID- 29956720
TI - Characteristics of circular RNA expression in lung tissues from mice with hypoxia
induced pulmonary hypertension.
AB - Pulmonary hypertension (PH) is a life-threatening lung disease, characterized by
an increase in pulmonary arterial pressure caused by vasoconstriction and
vascular remodeling. The pathogenesis of PH is not fully understood, and there is
a lack of potential biomarkers for the diagnosis and treatment of patients with
PH. Non-coding RNAs with a characteristic covalently closed loop structure,
termed circular RNAs (circRNAs), are present in a number of pulmonary diseases.
To the best of our knowledge, the present study is the first to use microarray
analysis to determine the expression profile of circRNAs in lung tissues from
mice with hypoxia-induced PH. In total, 23 significantly upregulated and 41
significantly downregulated circRNAs were identified. Of these, 12 differentially
expressed circRNAs were selected for further validation using reverse
transcription-quantitative polymerase chain reaction. Putative microRNAs (miRNAs)
that bind to the dysregulated circRNAs were predicted. Subsequently,
bioinformatics tools were used to construct circRNA-miRNA-mRNA networks for the
two most promising circRNAs, namely mmu_circRNA_004592 and mmu_circRNA_018351.
Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of target
genes of the dysregulated circRNAs revealed that these dysregulated circRNAs may
serve an important role in the pathogenesis of hypoxia-induced PH. Therefore,
these dysregulated circRNAs are candidate diagnostic biomarkers and potential
therapeutic targets for PH.
PMID- 29956721
TI - TERT promoter hypermethylation is associated with poor prognosis in
adrenocortical carcinoma.
AB - Telomere maintenance, most commonly achieved by telomerase activation through
induction of the telomerase reverse transcriptase (TERT) gene, is required for
cell immortalization, a hallmark of cancer. Adrenocortical carcinoma (ACC) is an
endocrine tumor for which TERT promoter mutations and telomerase activation have
been reported. The present study assessed alterations of the TERT gene locus and
telomere length in relation to clinical characteristics in ACC. In total, 38
cases of ACC with known TERT promoter mutational status were included. TERT
promoter methylation densities were assessed by pyrosequencing, and TERT copy
numbers and telomere length were determined by quantitative polymerase chain
reaction analysis, followed by comparison of the mRNA expression of TERT and
clinical parameters. The ACC tissue samples showed increased TERT copy numbers,
compared with normal adrenal tissue (NAT) samples (P=0.001). Mutually exclusive
TERT copy number gains or promoter mutation were present in 70% of the ACC
samples. The ACC tissues exhibited higher levels of CpG promoter methylation of
all eight CpG sites investigated within the -578 to -541 bp (Region A), compared
with the NATs (P=0.001). High methylation density at this region was associated
with metastatic disease and/or relapse, poor survival rates and higher European
Network for the Study of Adrenal Tumor stage (P<0.05). The mRNA expression of
TERT was inversely correlated with methylation density at -162 to -100 bp (Region
B). Correlation was observed between relative telomere length and the gene
expression of TERT. It was concluded that epigenetic alterations of the TERT
promoter are frequent and associated with advanced disease and poorer clinical
outcome in ACC.
PMID- 29956722
TI - A novel scoring system for acute myeloid leukemia risk assessment based on the
expression levels of six genes.
AB - Acute myeloid leukemia (AML) is the most common type of acute leukemia and is a
heterogeneous clonal disorder. At present, the pathogenesis of AML and potential
methods to effectively prevent AML have become areas of interest in research. In
the present study, two messenger ribonucleic acid sequencing datasets of patients
with AML were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus
databases. The differentially expressed genes (DEGs) of the poor and good
prognosis groups were screened using the Linear Models for Microarray Data
package, and the prognosis-related genes were screened using univariate Cox
regression analysis. A total of 206 significant DEGs were identified. Following
univariate and multivariate Cox regression analysis, 14 genes significantly
associated with prognosis were screened and six of these genes, including
triggering receptor expressed on myeloid cells 2 (TREML2), cysteine-glutamate
transporter (SLC7A11), NACHT, LRR, and PYD domains-containing protein 2 (NLRP2),
DNA damage-inducible transcript 4 protein (DDIT4), lymphocyte-specific protein 1
(LSP1) and C-type lectin domain family 11 member A (CLEC11A), were used to
construct model equations for risk assessment. The prognostic scoring system was
used to evaluate risk for each patient, and the results showed that patients in
the low-risk group had a longer survival time, compared with those in the high
risk group (P=9.59e-06 for the training dataset and P=0.00543 for the validation
dataset). A total of eight main Kyoto Encyclopedia of Genes and Genomes pathways
were identified, the top three of which were hematopoietic cell lineage, focal
adhesion, and regulation of actin cytoskeleton. Taken together, the results
showed that the scoring system established in the present study was credible and
that the six genes were identified, which were significantly associated with the
risk assessment of AML, offer potential as prognostic biomarkers. These findings
may provide clues for further clarifying the pathogenesis of AML.
PMID- 29956723
TI - Regulatory effects of the long non-coding RNA RP11-543N12.1 and microRNA-324-3p
axis on the neuronal apoptosis induced by the inflammatory reactions of
microglia.
AB - The present study aimed to examine how the long non-coding RNA (lncRNA) RP11
543N12.1 interacted with microRNA (miR)-324-3p to modify microglials (MIs)
induced neuroblastoma cell apoptosis, which may pose benefits to the treatment of
Alzhemier's disease (AD). The cell model of AD was established by treating SH
SY5Y cells with amyloid beta (Abeta)25-35, and MI were acquired using primary
cell culture technology. The lncRNAs that were differentially expressed between
SH-SY5Y and control cells were screened through a microarray assay and confirmed
via polymerase chain reaction. In addition, overexpression of RP11-543N12.1 and
miR-324-3p was established by transfection of SH-SY5Y cells with pcDNA3.1(+)-RP11
543N12.1 and miR-324-3p mimics, respectively, while downregulation of RP11
543N12.1 and miR-324-3p was achieved by transfection with RP11-543N12.1-small
interfering RNA (siRNA) and miR-324-3p inhibitor, respectively. The interaction
between RP11-543N12.1 and miR-324-3p was confirmed with a dual-luciferase
reporter gene assay. The results revealed that the expression levels of total and
phosphorylated tau in SH-SY5Y cells were significantly elevated following Abeta25
35 treatment (P<0.05), and RP11-543N12.1 was found to be differentially expressed
between the control and Abeta25-35-treated cells (P<0.05). Furthermore, the
targeted association of RP11-543N12.1 and miR-324-3p was predicted based on
miRDB4.0 and PITA databases, and then validated via the dual-luciferase reporter
gene assay. SH-SY5Y cells transfected with siRNA or inhibitor, and treated with
Abeta25-35 displayed cellular survival and apoptosis that were similar to the
normal levels (P<0.05). Finally, co-culture of MI and SH-SY5Y cells transfected
with RP11-543N12.1-siRNA/miR-324-3p inhibitor significantly enhanced cell
apoptosis (P<0.05). In conclusion, RP11-543N12.1 targeted miR-324-3p to suppress
proliferation and promote apoptosis in the AD cell model, suggesting that RP11
543N12.1 and miR-324-3p may be potential biomarkers and therapeutic targets for
AD.
PMID- 29956725
TI - Kushui Rose (R. Setate x R. Rugosa) decoction exerts antitumor effects in C.
elegans by downregulating Ras/MAPK pathway and resisting oxidative stress.
AB - Kushui rose (R. Setate x R. Rugosa) (KR) is a traditional Chinese medicine proven
to be a potent antioxidant, and used for thousands of years. Approximately 30% of
all human cancers relevant to mutational activated Ras, and over-activated Ras
are accompanied by increased accumulation of reactive oxygen species (ROS). Thus,
one way of developing anticancer drugs is to reduce ROS accumulation. Therefore,
KR was predicted to have potential to combat over-activated Ras-related cancer.
C. elegans with let-60(gf)/ras mutant, which exhibited tumor-like symptoms of the
multivulva phenotype, was employed to determine the effect of KR on Ras/MAPK
pathway. Other strains of worms and H2DCF-DA dye were also applied to study the
antioxidant stress capacity of KR. This study was aimed to determine whether KR
has a potential effect on combat over-activated Ras-related cancer through
resistance to oxidative stress. Our results showed that Kushui rose decoction
(KRD) has potent antioxidant activity in vitro, and can inhibit over-activated
Ras in vivo. Further, KRD significantly suppressed over-activated Ras/MAPK
pathway by regulating oxidative stress-related proteins, such as forkhead
transcription factor (DAF-16), glutathione S-transferase-4 (GST-4), superoxide
dismutases (SODs) and heat shock protein-16.2 (HSP-16.2). However, essential oil
and hydrosol of KR had no effect on over-activated Ras. Thus these results
reminded us that people usually soak rose in hot water to prepare 'rose tea' as
an effective way for health care. Thus, KRD was demonstrated to be a potential
drug candidate for combating over-activated Ras-related cancer as an antioxidant.
PMID- 29956724
TI - Effect of ABT-888 on the apoptosis, motility and invasiveness of BRAFi-resistant
melanoma cells.
AB - Melanoma is a molecularly heterogeneous disease with many genetic mutations and
altered signaling pathways. Activating mutations in the BRAF oncogene are
observed in approximately 50% of cutaneous melanomas and the use of BRAF
inhibitor (BRAFi) compounds has been reported to improve the outcome of patients
with BRAF-mutated metastatic melanoma. However, the majority of these patients
develop resistance within 6-8 months following the initiation of BRAFi treatment.
In this study, we examined the possible use of the poly(ADP-ribose) polymerase 1
(PARP1) inhibitor, ABT-888 (veliparib), as a novel molecule that may be
successfully employed in the treatment of BRAFi-resistant melanoma cells.
Sensitive and resistant to BRAFi dabrafenib A375 cells were exposed to increasing
concentrations of ABT-888. Cell viability and apoptosis were assessed by MTT
assay and Annexin V-FITC analysis, respectively. The cell migratory and invasive
ability was investigated using the xCELLigence technology and Boyden chamber
assays, respectively. ABT-888 was found to reduce cell viability and exhibited
pro-apoptotic activity in melanoma cell lines, independently from the BRAF/NRAS
mutation status, in a dose-dependent manner, with the maximal effect being
reached in the 25-50 uM concentration range. Moreover, ABT-888 promoted apoptosis
in both the sensitive and resistant A375 cells, suggesting that ABT-888 may be
useful in the treatment of BRAFi-resistant subsets of melanoma cells. Finally, in
accordance with the involvement of PARP1 in actin cytoskeletal machinery, we
found that the cytoskeletal organization, motility and invasive capability of
both the A375 and A375R cells decreased upon exposure to 5 uM ABT-888 for 24 h.
On the whole, the findings of this study highlight the pivotal role of PARP1 in
the migration and invasion of melanoma cells, suggesting that ABT-888 may indeed
be effective, not only as a pro-apoptotic drug for use in the treatment of BRAFi
resistant melanoma cells, but also in suppressing their migratory and invasive
activities.
PMID- 29956726
TI - Curcumin attenuates resistance to irinotecan via induction of apoptosis of cancer
stem cells in chemoresistant colon cancer cells.
AB - Resistance to conventional chemotherapeutic agents, including irinotecan (CPT
11), 5-fluorouracil and capecitabine is a major cause for therapeutic failure in
patients with colorectal cancer (CRC). Increasing evidence has demonstrated that
cancer cells exhibiting stem cell-like characteristics are associated with the
development of resistance to chemotherapeutic agents. As a plant polyphenol,
curcumin has been demonstrated to have the ability to ameliorate resistance of
CRC to chemotherapeutic agents, but the associations among curcumin, cancer stem
cells (CSCs) and chemoresistance of CRC remain unclear. The present study
established a CPT-11-resistant colon cancer cell line, LoVo/CPT-11 cells, and
detected the expression levels of CSC identification markers [cluster of
differentiation (CD)44, CD133, epithelial cell adhesion molecule (EpCAM) and
CD24] in parental cells and CPT-11-resistant cells. It was revealed that the
expression levels of the colon CSC markers in LoVo/CPT-11 cells were
significantly higher compared those in parental cells at the mRNA and protein
level. The effect of curcumin on the chemoresistance to CPT-11 and the expression
levels of CSC identification markers in LoVo/CPT-11 cells separately treated with
curcumin and CPT-11 were further investigated. The results revealed that curcumin
significantly attenuated chemoresistance to CPT-11, and treatment with curcumin
resulted in a significant reduction of the expression levels of CSC
identification markers. Furthermore, a tumor sphere formation assay was used to
enrich colon CSCs from LoVo/CPT-11 cells, and demonstrated that curcumin
efficiently diminished the traits of colon CSCs, as evidenced by the inability to
form tumor spheres, the reduction in the expression of CSC identification
markers, and apoptosis-induced effects on sphere-forming cells treated with
curcumin alone or in combination with CPT-11. Altogether, the present data
demonstrated that curcumin attenuated resistance to chemotherapeutic drugs
through induction of apoptosis of CSCs among colon cancer cells. These findings
may provide novel evidence for the therapeutic application of curcumin in CRC
intervention.
PMID- 29956727
TI - Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via
CIP2A/PP2A/ERK signaling in prostate cancer.
AB - Polyphyllin I (PPI) is a natural compound extracted from the rhizomes of Paris
polyphylla and has been used to treat fevers and headaches in China. In the
present study, the antitumor activity of PPI in prostate cancer (PC) cells was
evaluated. At low doses, PPI decreased proliferation, invasion and epithelial
mesenchymal transition (EMT) in PC cells. PPI decreased the expression of matrix
metalloproteinase 7 (MMP7), an enzyme that is critical for tumor metastasis. PPI
also decreased the expression of Snail and vimentin, which are EMT-associated
factors. Additionally, PPI suppressed AP-1 transcriptional activity and AP-1
binding to the MMP7 and vimentin promoters. The results demonstrated that PPI
downregulated the phosphorylation of extracellular signaling-related kinase
(ERK), which is upstream modulator of AP-1. The results of the present study
demonstrated that PPI may inhibit the cancerous inhibitor of protein phosphatase
2A (CIP2A)/protein phosphatase 2A (PP2A)/ERK axis, downregulate the expression of
MMP7, vimentin, and Snail, and suppress tumor invasion and EMT. A PC xenograft
mouse model was employed and the results revealed that PPI may decrease tumor
growth and weight. Additionally, PPI may inhibit proliferating cell nuclear
antigen expression and CIP2A/PP2A/ERK signaling pathway in PPI-treated tumors.
Therefore, the results of the present study suggest that PPI may suppress the
growth, invasion and EMT of PC cells via inhibition of CIP2A/PP2A/ERK signaling
axis. As a result, PPI may be a novel target for the treatment of PC.
PMID- 29956728
TI - Detection of dysregulated competing endogenous RNA modules associated with clear
cell kidney carcinoma.
AB - Recent evidence has suggested that competitive endogenous RNAs (ceRNAs) are
important regulatory molecules in clear cell kidney carcinoma (KIRC) and their
dysregulation may contribute to cancer pathogenesis. However, the critical roles
of dysregulated ceRNAs in KIRC remain unknown. In the present study, a KIRC
dysregulated ceRNA-ceRNA network (KDCCNet) was constructed based on the 'ceRNA
hypothesis' by integrating microRNA regulation and expression profiles in
cancerous and normal tissues. Two dysregulated patterns of ceRNAs interaction
(gain and loss) exist in KDCCNet. The two modules, which are 95% loss
interactions and 97% gain interactions, were demonstrated to be able to
distinguish normal samples from cancer samples. Two long non-coding (lnc)-RNAs
(glucuronidase beta pseudogene 11 and LIFR antisense RNA 1) demonstrated
significant associations with KIRC prognosis. The present study of the KDCCNet
revealed a novel biological mechanism for KIRC and provides novel lncRNAs as
candidate prognostic biomarkers.
PMID- 29956729
TI - Pyroptosis, a novel mechanism implicated in cataracts.
AB - An understanding of the mechanism of cataract formation may reduce its burden on
medical care worldwide. It is established that pyroptosis is associated with
oxidative stress, one of the causes of cataracts, and may provide novel
therapeutic targets for the treatment of cataracts. The present study therefore
investigated the role of pyroptosis in cataract formation. SRA01/04 human lens
epithelium cells (HLECs) were treated with H2O2 and cell viability was assessed
by an MTT assay. Pyroptosis in HLECs was examined by TUNEL staining, and the
expression of caspase-1 and interleukin (IL)-1beta was determined using reverse
transcription-quantitative polymerase chain reaction (RT-qPCR), western blot
analysis and immunostaining. A caspase-1 inhibitor was used to investigate the
effects of caspase-1 downregulation. In addition, the expression of caspase-1 and
IL-1beta in lens anterior capsule tissue samples from patients with cataracts and
normal controls was also analyzed by immunostaining, RT-qPCR and western blot
analysis. The results demonstrated that pyroptosis in H2O2-treated HLECs, and the
mRNA and protein expression of caspase-1 and IL-1beta, was significantly
increased compared with control cells. Furthermore, caspase-1 and IL-1beta
expression was significantly increased in cataract tissue samples compared with
normal controls. When HLECs were cotreated with a caspase-1 inhibitor and 100 uM
H2O2, caspase-1 and IL-1beta expression were decreased compared with the 100 uM
H2O2-only group. In conclusion, the results of the present study demonstrate that
pyroptosis may have a role in cataract formation, and the caspase-1 and IL-1beta
pathways may be involved in this pathological process. Pyroptosis appears to be a
promising target in the prevention of cataract formation.
PMID- 29956731
TI - Quercetin-3-methyl ether suppresses human breast cancer stem cell formation by
inhibiting the Notch1 and PI3K/Akt signaling pathways.
AB - Breast cancer is a leading cause of mortality among women with cancer worldwide.
Quercetin-3-methyl ether, a natural compound occurring in various plants, has
been indicated to have potent anticancer activity. Breast cancer cell growth and
survival were examined by CCK-8 and colony formation assay, whilst cell cycle and
apoptosis were determined by flow cytometry. Cell invasion and migration were
assessed by wound-healing assay and Transwell assay. Cancer stem cell formation
was analyzed by mammosphere formation assay and related signaling pathways were
detected by western blotting. In the present study, it was observed that
treatment with quercetin-3-methyl ether significantly inhibited cell growth,
induced apoptosis and cell cycle arrest at the G2-M phase, and suppressed
invasion and migration in human breast cancer cells, including the triple
negative MDAMB-231 cell line, and the estrogen receptor-positive/progesterone
receptor-positive/human epidermal growth factor receptor 2-negative MCF-7 and
T47D cell lines. This compound also markedly suppressed the epithelial
mesenchymal transition process as evidenced by the upregulated expression of E
cadherin, and the concomitant downregulated expression of vimentin and MMP-2.
Furthermore, it was demonstrated that quercetin-3-methyl ether treatment
inhibited mammosphere formation and the expression of the stemness-related genes,
SRY-box 2 and Nanog. Mechanistically, this compound decreased the expression of
Notch1, and induced the phosphorylation of phosphoinositide 3-kinase (PI3K) and
Akt. It also attenuated the human insulin growth factor 1-induced phosphorylation
of PI3K, Akt and glycogen synthase kinase beta. Additionally, the combination of
quercetin-3-methyl ether and a secretase inhibitor (DAPT) exhibited additive
suppression of the expression of Notch1, PI3K, Akt and mammalian target of
rapamycin and a more marked inhibitory effect on cell proliferation and colony
formation compared with either drug alone. Treatment with quercetin-3-methyl
ether alone markedly suppressed the levels of tri-methyl histone H3 (Lys27), but
had no effect on the expression of enhancer of zeste homolog 2. Overall, these
findings indicated that quercein-3-methyl ether may be a potential therapeutic
compound for the treatment of triple negative and hormone-sensitive breast
cancer.
PMID- 29956730
TI - High COX-2 expression contributes to a poor prognosis through the inhibition of
chemotherapy-induced senescence in nasopharyngeal carcinoma.
AB - Resistance to radiotherapy and chemotherapy currently represents one of the major
reasons for therapeutic failure in nasopharyngeal carcinoma (NPC). However, the
mechanisms underlying resistance to chemotherapy in NPC remain unclear. In this
study, cell counting assay, cell cycle assay and senescence associated beta
galactosidase activity were performed to evaluate cell growth, proliferation and
senescence, respectively. We found that the aberrant expression of cyclooxygenase
2 (COX-2) was associated with a poor outcome and recurrance in patients with NPC.
In NPC cells, COX-2 overexpression increased cell proliferation, inhibited
cellular senescence and resulted in chemoresistance, while the knockdown of COX-2
reduced cell proliferation, promoted cellular senescence and overcame
chemoresistance. Furthermore, fibroblasts from COX-2 knockout mice exhibited
cellular senescence, particularly when treated with chemotherapeutic agents.
Mechanistically, COX-2 interacted with p53 protein and inhibited cellular
senescence, which resulted in chemotherapeutic resistance. On the whole, these
findings indicate that COX-2 may play a critical role in chemotherapeutic
resistance in NPC via the inhibition of chemotherapy-induced senescence via the
inactivation of p53. This study provides experimental evidence for the
preclinical value of increasing chemotherapy-induced senescence by targeting COX
2 as an effective antitumor treatment in patients with recurrent NPC.
PMID- 29956732
TI - Single-walled carbon nanohorn aggregates promotes mitochondrial dysfunction
induced apoptosis in hepatoblastoma cells by targeting SIRT3.
AB - Single-walled carbon nanohorns (SWNHs) can accumulate in a variety of cell types
or tissues and exert biological effects, which have been demonstrated to induce
apoptosis in hepatoblastoma cells. However, the role and molecular mechanisms of
SWNHs remain unclear. The mitochondrion is an important subcellular structure and
may contribute to apoptosis that is induced by SWNHs in hepatoblastoma cells. To
address this question, the mitochondrial function of HepG2 or L02 cells that were
treated with SWNHs was examined. The results indicated that SWNHs were able to
decrease the mitochondrial membrane potential and suppress the activity of the
Na+/K+-ATPase. Secondly, HepG2 cells and L02 cells were treated with SWNHs in
vivo and in vitro. The expression of mitochondrial-associated proteins [acyl-CoA
synthetase short chain family member 1, Bax, cytochrome C (CYT-C), sodium channel
epithelial 1alpha subunit, sirtuin 3 (SIRT3) and voltage-dependent anion channel
1] was analyzed by western blotting and immunohistochemical staining. The results
revealed that SWNH treatment was able to alter the expression of multiple
mitochondrial apoptotic pathway-associated proteins in HepG2 cells. SWNH
treatment was able upregulate the expression of SIRT3, CYT-C and VDAC1 and
downregulate the expression of AceCS2, but it had a more stable effect on SIRT3.
However, similar findings were not observed in L02 cells. Therefore, the data
from the present study indicated that SWNHs might be used as a safe anticancer
agent, where it is able to trigger mitochondrial dysfunction-induced apoptosis by
upregulating SIRT3 expression in HepG2 cells.
PMID- 29956733
TI - GDF-15 prevents LPS and D-galactosamine-induced inflammation and acute liver
injury in mice.
AB - Growth differentiation factor-15 (GDF-15) is a transforming growth factor (TGF)
beta superfamily member with a poorly characterized biological activity,
speculated to be implicated in several diseases. The present study aimed to
determine whether GDF-15 participates in sepsis-induced acute liver injury in
mice. Lipopolysaccharide (LPS) and D-galactosamine (D-GalN) were administered to
mice to induce acute liver injury. Survival of mice, histological changes in
liver tissue, and levels of inflammatory biomarkers in serum and liver tissue
were evaluated following treatment with GDF-15. The underlying mechanism was
investigated by western blotting, ELISA, flow cytometry, and reverse
transcription-quantitative polymerase chain reaction using Kupffer cells. The
results demonstrated that GDF-15 prevented LPS/D-GalN-induced death, increase in
inflammatory cell infiltration and serum alanine aminotransferase and aspartate
aminotransferase activities. In addition, GDF-15 treatment reduced the production
of hepatic malondialdehyde and myeloperoxidase, and attenuated the increase of
interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-1beta expression in
serum and liver tissue, accompanied by inducible nitric oxide synthase (iNOS)
inactivation in the liver. Similar changes in the expression of inflammatory
cytokines, IL-6, TNF-alpha and IL-1beta, and iNOS activation were observed in the
Kupffer cells. Further mechanistic experiments revealed that GDF-15 effectively
protected against LPS-induced nuclear factor (NF)-kappaB pathway activation by
regulating TGFbeta-activated kinase 1 (TAK1) phosphorylation in Kupffer cells. In
conclusion, GDF-15 reduced the activation of pro-inflammatory factors, and
prevented LPS-induced liver injury, most likely by disrupting TAK1
phosphorylation, and consequently inhibiting the activation of the NF-kappaB
pathway in the liver.
PMID- 29956734
TI - MicroRNA-26a protects vascular smooth muscle cells against H2O2-induced injury
through activation of the PTEN/AKT/mTOR pathway.
AB - Abdominal aortic aneurysm (AAA) is a common disease, which is characterized by
the apoptosis of vascular smooth muscle cells (VSMCs). In previous years,
microRNAs (miRNAs) have been associated with AAA and functionally implicated in
the pathogenesis of this disease. However, the role of miRNAs in the apoptosis of
VSMCs remains to be fully elucidated. The present study aimed to elucidate the
role and mechanism of miRNAs in protecting against hydrogen peroxide (H2O2)
induced apoptosis in VSMCs. The expression of miRNAs in peripheral blood from
patients diagnosed with AAA was analyzed using a microarray and reverse
transcription polymerase chain reaction. A VSMC injury model induced by H2O2 was
used to determine the potential role of miR-26a against cell injury. Cell
viability, cell apoptosis and reactive oxygen species (ROS) generation were
determined by a CCK8 assay, flow cytometry and a 2',7'-DCF diacetate assay,
respectively. It was observed that miRNA (miR)-26a (miR-26a-1-5p) was
significantly downregulated in peripheral blood samples from patients with AAA.
It was revealed that H2O2 treatment dose-dependently inhibited cell viability,
enhanced apoptosis and induced the production of ROS, which indicated the success
of the model establishment. It was also observed that miR-26a was downregulated
in the VSMCs following H2O2 stimulation. The upregulation of miR-26a attenuated
H2O2-induced cell injury, as evidenced by the enhancement of cell viability, and
inhibition of the activity of caspase-3, apoptosis and ROS production. In
addition, phosphatase and tensin homolog (PTEN), a well-known regulator of the
AKT/mammalian target of rapamycin (mTOR) pathway, was found to be a direct target
of miR-26a in the VSMCs and this was validated using a luciferase reporter assay.
Overexpression of PTEN by pcDNA-PTEN plasmids markedly eliminated the protective
effects of the overexpression of miR-26a on H2O2-induced cell injury. Finally, it
was found that miR-26a mediated its anti-apoptotic action by reactivation of the
AKT/mTOR pathway, as demonstrated by the upregulation of phosphorylated (p-)AKT
and p-mTOR, and the Akt inhibitor API-2 reversing the protective effects on VSMCs
mediated by miR-26a. These results indicated that miR-26a protected VSMCs against
H2O2-induced injury through activation of the PTEN/AKT/mTOR pathway, and miR-26a
may be considered as a potential prognostic biomarker and therapeutic target in
the treatment of AAA.
PMID- 29956735
TI - KRAB zinc-finger protein 382 regulates epithelial-mesenchymal transition and
functions as a tumor suppressor, but is silenced by CpG methylation in gastric
cancer.
AB - Several studies have recently reported that KRAB zinc finger protein 382 (ZNF382)
is downregulated in multiple carcinoma types due to promoter methylation. The
exact role of ZNF382 in gastric carcinogenesis, however, remains elusive. In this
study, we investigated the alterations and functions of ZNF382 in the
pathogenesis of gastric cancer (GC). Semi-quantitative reverse transcription
polymerase chain reaction (RT-PCR), quantitative (real-time) PCR (qPCR) and
immunohistochemistry were carried out to detect the expression patterns of ZNF382
in GC cell lines and gastric tissue samples. Furthermore, its methylation status
in GC cell lines, tumor tissues and adjacent non-tumor tissues was detected by
methylation-specific PCR (MSP). We observed that ZNF382 was silenced due to
promoter methylation in MKN45 and SGC7901 cell lines, and that its silencing
could be reversed with 5-aza-2'-deoxycytidine, indicating that its downregulation
in GC is due to promoter methylation. In addition, the ectopic expression of
ZNF382 significantly inhibited gastric tumor cell clonogenicity, proliferation,
migration and epithelial-mesenchymal transition (EMT) through the induction of
apoptosis. ZNF382 expression downregulated the expression of SNAIL, Vimentin,
Twist, NOTCH1, NOTCH2, NOTCH3, NOTCH4, HES-1, JAG1, matrix metalloproteinase
(MMP)2 and MMP11, as well as that of the stem cell markers, NANOG, octamer
binding transcription factor 4 (OCT4) and SOX2. ZNF382 also upregulated the
expression of E-cadherin. On the whole, the findings of this study suggest that
ZNF382 functions as a tumor suppressor in GC cells, but is frequently methylated
in both GC cell lines and primary gastric tumors. ZNF382 can reverse the EMT
process in GC cells through NOTCH signaling. Our findings further illustrate the
molecular pathogenesis of GC and establish potential biomarkers for this type of
cancer.
PMID- 29956736
TI - Reversal of the Warburg effect with DCA in PDGF-treated human PASMC is
potentiated by pyruvate dehydrogenase kinase-1 inhibition mediated through
blocking Akt/GSK-3beta signalling.
AB - There is accumulating evidence indicating that the growth inhibitory effect of
dichloroacetate (DCA) on pulmonary arterial smooth muscle cells (PASMCs) may be
associated with the reversal of the Warburg effect and initiation of the
mitochondria-dependent apoptotic pathway. Previous studies indicated that
platelet-derived growth factor (PDGF) promoted the Warburg effect and resulted in
apoptotic resistance of PASMCs, which was attributed to activation of the
phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signalling pathway.
However, the mechanism underlying the pro-apoptotic effect of DCA on PDGF-treated
PASMCs has not been thoroughly elucidated, and the effect of the Akt/glycogen
synthase kinase-3beta (GSK-3beta) pathway inhibition concomitant with the effect
of DCA on PASMC proliferation remains unclear. The growth of human PASMCs and the
lactate concentration in extracellular medium of PASMCs were detected by Cell
Counting Kit-8 assays and a Lactate Colorimetric Assay kit, respectively. Cell
apoptosis was evaluated by fluorescence activated cell sorting. The mitochondrial
membrane potential (DeltaPsim) was assessed with 5,5',6,6'-tetrachloro-1,1',3,3'
tetraethylbenzimidazol-carbocyanine iodide assays. The expression levels of
phosphorylated Akt and GSK-3beta, pyruvate dehydrogenase, cleaved caspase-3,
pyruvate dehydrogenase kinase-1 (PDK-1), hypoxia inducible factor-1alpha (HIF
1alpha) and hexokinase-2 (HK-2) were measured with western blot analysis.
Confocal analyses were employed to determine HK-2 co-localisation with the
mitochondria. The results indicated that DCA inhibited human PASMC proliferation
in a dose-dependent manner. DCA at 10 mM promoted apoptosis and the upregulation
of activated caspase-3 in PASMCs pre-treated with 20 ng/ml PDGF-homeodimer BB
(BB). Treatment with 5 uM LY294002 produced minimal anti-proliferative effects on
human PASMCs and barely induced cellular apoptosis and caspase-3 activation.
However, co-administration of 10 mM DCA with LY294002 significantly decreased the
cell proliferation index and induced cell apoptosis and caspase-3 activation. The
combined administration of LY294002 with DCA significantly decreased lactate
concentration, promoted the depolarisation of the DeltaPsim and repressed HIF
1alpha upregulation and HK-2 activation in PASMCs treated with PDGF, which was
attributed to the potentiation of DCA-induced PDK-1 inhibition by LY294002 via
blockade of the Akt/GSK-3beta/HIF-1alpha signalling pathway. In conclusion,
inhibition of the Akt/GSK-3beta pathway improved the pro-apoptotic effect of DCA
on human PASMCs, which may be attributed to a reversal of the Warburg effect by
blocking the mutual interaction between HIF-1alpha and PDK-1, consequently
downregulating HK-2. Therefore, combinatory treatment with DCA and PI3K
inhibitors may represent a novel therapeutic strategy for the reversal of
apoptosis resistance exhibited by PASMCs as a result of mitochondrial
bioenergetic abnormalities, as well as the treatment of pulmonary vascular
remodelling in pulmonary arterial hypertension.
PMID- 29956737
TI - MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis
via downregulating HMGB1.
AB - The downregulation of microRNA (miR)-381 has been detected in various diseases.
The present study aimed to investigate the effects, and underlying mechanisms of
miR-381 on inflammation and macrophage infiltration in polymyositis (PM). A mouse
model of experimental autoimmune myositis (EAM) was generated in this study.
Hematoxylin and eosin staining was conducted to detect the inflammation of muscle
tissues. In addition, ELISA and immunohistochemistry were performed to determine
the expression levels of associated factors, and reverse transcription
quantitative polymerase chain reaction and western blotting were used to detect
the expression levels of related mRNAs and proteins. A luciferase activity assay
was used to confirm the binding of miR-381 and high mobility group box 1 (HMGB1)
3' untranslated region. Transwell assays were also performed to assess the
migratory ability of macrophages. The results demonstrated that serum creatine
kinase (s-CK), HMGB1 and cluster of differentiation (CD)163 expression in
patients with PM were increased compared within healthy controls. Conversely, the
expression levels of miR-381 were downregulated in patients with PM. Furthermore,
high HMGB1 expression was associated with poor survival rate in patients with PM.
In the mouse studies, muscle inflammation and CD163 expression were decreased in
the anti-IL-17 and anti-HMGB1 groups, compared with in the EAM model group. The
expression levels of s-CK, HMGB1, IL-17 and intercellular adhesion molecule
(ICAM)-1 were also downregulated in response to anti-IL-17 and anti-HMGB1. These
findings indicated that HMGB1 was closely associated with inflammatory responses.
In addition, the present study indicated that transfection of macrophages with
miR-381 mimics reduced the migration of inflammatory macrophages, and the
expression levels of HMGB1, IL-17 and ICAM-1. Conversely, miR-381 inhibition
exerted the opposite effects. The effects of miR-381 inhibitors were reversed by
HMGB1 small interfering RNA. In conclusion, miR-381 may reduce inflammation and
the infiltration of macrophages; these effects were closely associated with the
downregulation of HMGB1.
PMID- 29956739
TI - MicroRNA-494 acts as a tumor suppressor in pancreatic cancer, inhibiting
epithelial-mesenchymal transition, migration and invasion by binding to SDC1.
AB - Pancreatic cancer (PC) is the fourth most common cause of cancer-related
mortality in the industrialized world. Emerging evidence indicates that a variety
of microRNAs (miRNAs or miRs) are involved in the development of PC. The aim of
the present study was to elucidate the mechanisms through which miR-494 affects
the epithelial-mesenchymal transition (EMT) and invasion of PC cells by binding
to syndecan 1 (SDC1). PC tissues and pancreatitis tissues were collected, and the
regulatory effects of miR-494 on SDC1 were validated using bioinformatics
analysis and a dual-luciferase report gene assay. The cell line with the highest
SDC1 expression was selected for use in the following experiments. The role of
miR-494 in EMT was assessed by measuring the expression of SDC1, E-cadherin and
vimentin. Cell proliferation was assessed using a cell counting kit (CCK)-8
assay, migration was measured using a scratch test, invasion was assessed with a
Transwell assay and apoptosis was detected by flow cytometry. Finally, a
xenograft tumor model was constructed in nude mice to observe tumor growth in
vivo. We found that SDC1 protein expression was significantly higher in the PC
tissues. SDC1 was verified as a target gene of miR-494. The SW1990 cell line was
selected for use in further experiments as it had the lowest miR-494 expression
and the highest SDC1 expression. Our results also demonstrated that miR-494
overexpression and SDC1 silencing significantly decreased the mRNA and protein
expression of SDC1 and vimentin in SW1990 cells, while it increased E-cadherin
expression and apoptosis, and inhibited cell growth, migration, invasion and
tumor growth. On the whole, the findings of this study demonstrated that miR-494
is able to downregulate SDC1 expression, thereby inhibiting the progression of
PC. These findings reveal a novel mechanism through which miR-494 affects the
development of PC and may thus provide a basis for the application of miR-494 in
pancreatic oncology.
PMID- 29956738
TI - Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF
kappaB/COX-2 signaling pathways by targeting leucine 281 and leucine 25 in
IKKbeta in renal cell carcinoma.
AB - Parthenolide (PTL) is a sesquiterpene lactone compound obtained from Tanacetum
parthenium (feverfew) and inhibits the activation of nuclear factor (NF)-kappaB.
Epoxymicheliolide (EMCL) is a compound which is structurally related to PTL;
however, EMCL is more stable under acidic and alkaline conditions. As a
biologically active molecule, the detailed mechanism by which EMCL inhibits tumor
activity remains to be elucidated. The present study evaluated the effect of EMCL
on renal cell carcinoma (RCC) cells and identified the underlying mechanisms. It
was found that treatment with EMCL significantly inhibited the proliferation of
RCC cells in vitro and increased the induction of apoptosis by activating the
mitochondria- and caspase-dependent pathway. Simultaneously, EMCL suppressed cell
invasion and metastasis by inhibiting epithelial-mesenchymal transition, as
observed in a microfluidic chip assay. Furthermore, using immunofluorescence
analysis, an electrophoretic mobility shift assay and a dual-luciferase reporter
assay, it was shown that treatment with EMCL significantly suppressed the
expression of cyclooxygenase-2 by inhibiting the translocation of NF-kappaB
p50/p65 and the activity of NF-kappaB. Collectively, the results indicated that
EMCL suppressed tumor growth by inhibiting the activation of NF-kappaB and
suggested that EMCL may be a novel anticancer agent in the treatment of RCC.
PMID- 29956740
TI - Sox2 promotes tumor aggressiveness and epithelial-mesenchymal transition in
tongue squamous cell carcinoma.
AB - Tongue squamous cell carcinoma (TSCC) is highly malignant and poorly
differentiated, resulting in a high frequency of local recurrence and distant
metastases. Sox2 (Sry-box2), an important factor in embryonic development and
cell differentiation, has been shown to associate with malignant phenotypes and
epithelial-mesenchymal transition (EMT) progression in numerous types of human
tumors. However, the clinical relevance and molecular mechanisms of Sox2 in TSCC
remain unclear. In the present study, the expression levels of Sox2 were assessed
in 61 pairs of TSCC samples and corresponding adjacent non-cancerous tissues
using immunohistochemical methods. Associations between Sox2 expression and
clinicopathological features were evaluated. Furthermore, Sox2 was overexpressed
and inhibited using full-length Sox2 cDNA and short hairpin RNA (shRNA)
transfection in UM2 and Cal27 cell lines, respectively. The malignant phenotypes
were assessed by plate clone formation assays, wound-healing assays and Transwell
assays. EMT markers (E-cadherin, vimentin, Twist, Slug and Snail) and beta
catenin were detected by reverse transcription-polymerase chain reaction and
western blot analysis following the alterations of Sox2 expression. The results
indicated that Sox2 expression was markedly upregulated in TSCC samples and was
significantly associated with tumor growth (pT stage), cell differentiation,
lymphatic metastasis (pN stage) and clinical stage (pTNM stage). Cal27-shRNA-Sox2
cells not only exhibited a decreased capacity for cell proliferation, but also
suppressed cell migration and invasion, and an attenuated colony formation
capacity. By contrast, UM2-Sox2 cells exhibited accelerated cell malignant
phenotypes and EMT progression. Moreover, when the expression of Sox2 was
decreased by shRNA transduction, beta-catenin expression was attenuated. An
opposing phenomenon was observed in UM2-Sox2 cells. In conclusion, this study
suggests that Sox2 expression serves a role in TSCC malignant phenotypes and EMT
progression, and that beta-catenin may act as a modulated factor in this
progression.
PMID- 29956741
TI - Prolonged survival of patients with colorectal cancer is associated with a higher
regucalcin gene expression: Overexpression of regucalcin suppresses the growth of
human colorectal carcinoma cells in vitro.
AB - Regucalcin plays a crucial role as a regulator of transcriptional signaling
activity, and its decreased expression or activity may contribute to the
promotion of human carcinogenesis. A higher regucalcin expression in the tumor
tissues has been demonstrated to prolong the survival of patients with various
types of cancer, including pancreatic cancer, breast cancer, liver cancer and
lung adenocarcinoma. The involvement of regucalcin in human colorectal cancer was
investigated in the current study. Regucalcin gene expression and the survival
data of 62 patients with colorectal cancer were obtained though the Gene
Expression Omnibus (GEO) database (GSE12945) for outcome analysis. The data of
gene expression revealed that the prolonged survival of patients with colorectal
cancer was associated with a higher regucalcin gene expression in tumor tissues.
The overexpression of regucalcin suppressed colony formation and proliferation,
and induced the death of human colorectal carcinoma RKO cells cultured in a
medium containing fetal bovine serum in vitro. Mechanistically, the
overexpression of regucalcin induced the G1 and G2/M phase cell cycle arrest of
the RKO cells through the suppression of multiple signaling pathways, including
Ras, Akt, mitogen-activated protein (MAP) kinase and SAPK/JNK. Of note, the
overexpression of regucalcin induced an increase in the levels of the tumor
suppressors, p53 and Rb, and the cell cycle inhibitor, p21. Moreover, the levels
of the transcription factors, c-fos, c-jun, nuclear factor (NF)-kappaB p65, beta
catenin and signal transducer and activator of transcription 3 (Stat3), were
suppressed by the overexpression of regucalcin. On the whole, the findings of
this study suggest that regucalcin plays a crucial role as a suppressor in human
colorectal cancer, and that the suppressed expression of the regucalcin gene may
predispose patients to the promotion of colorectal cancer. The overexpression of
regucalcin by gene delivery may thus prove to be a novel therapeutic strategy for
colorectal cancer.
PMID- 29956742
TI - Identification of cisplatin sensitizers through high-throughput combinatorial
screening.
AB - cis-Diamminedichloroplatinum/cisplatin (CDDP) is a major drug used in cancer
chemotherapy; however, the toxic side-effects and development of drug resistance
represent major challenges to the clinical use of CDDP. The aim of the present
study was to identify effective drug combination regimens through high-throughput
drug screening that can enhance the efficacy of CDDP, and to investigate the
underlying mechanisms. A cell-based high-throughput screening methodology was
implemented, using a library of 1,280 Food and Drug Administration (FDA)-approved
drugs, to identify clinical compounds that act synergistically with CDDP. Our
study identified two compounds, namely potassium antimony tartrate and topotecan,
that significantly enhanced the sensitivity of colorectal and non-small cell lung
cancer cells to CDDP. The synergistic action of both compounds with CDDP was
confirmed by further quantitative analyses. Topotecan is a topoisomerase-1
inhibitor that has previously been shown to enhance the clinical response and
overall patient survival when combined with CDDP by a yet unclear mechanism. We
demonstrated that the combination of topotecan with CDDP significantly inhibited
colony formation ability and increased the apoptosis of several cancer cell
lines. Mechanistic analyses revealed that topotecan enhanced CDDP-induced DNA
damage and inhibited the repair of DNA strand breaks, without affecting the
cellular platinum content. Overall, the findings of this study demonstrated that
the use of the FDA-approved drug panel in high-throughput screening is an
effective method for identifying effective therapeutic regimens that are
clinically relevant, and may have high feasibility for translation into clinical
practice.
PMID- 29956743
TI - Prostaglandin EP2 receptor: Novel therapeutic target for human cancers (Review).
AB - Prostaglandin E2 (PGE2) receptor 2 subtype (EP2), which is a metabolite of
arachidonic acid that binds with and regulates cellular responses to PGE2, is
associated with numerous physiological and pathological events in a wide range of
tissues. As a stimulatory G protein-coupled receptor, PGE2-induced EP2 activation
can activate adenylate cyclase, leading to increased cytoplasmic cAMP levels and
activation of protein kinase A. The EP2 receptor can also activate the glycogen
synthase kinase 3beta and beta-catenin pathways. The present study aimed to
review the roles of the EP2 receptor in tumor development, including immunity,
chronic inflammation, angiogenesis, metastasis and multidrug resistance.
Furthermore, the involvement of the EP2 receptor signaling pathway in cancer was
discussed. Understanding the role and mechanisms of action of the EP2 receptor,
and its importance in targeted therapy, may help identify novel methods to
improve management of numerous types of cancer.
PMID- 29956744
TI - Protective effect of morin on myocardial ischemia-reperfusion injury in rats.
AB - Morin, a natural flavonol, exhibits antioxidative, anti-inflammatory and anti
apoptotic effects in various pathological and physiological processes. However,
whether morin exerts a protective effect on myocardial ischemia-reperfusion
injury (MIRI) is unknown. The present study aimed to determine the effect of
morin on MIRI in cultured cardiomyocytes and isolated rat hearts, and to
additionally explore the underlying mechanism. The effect of morin on the
viability, lactate dehydrogenase (LDH) activity and apoptosis of H9c2
cardiomyocytes subjected to hypoxia/reoxygenation, and cardiac function and
infarct size of rat hearts following ischemia/reperfusion in an animal model were
measured. Furthermore, the mitochondrial permeability transition pore (MPTP)
opening, mitochondrial membrane potential (DeltaPsim), and the change in the
expression levels of B-cell lymphoma 2 (Bcl2)-associated X protein (Bax), Bcl-2
and mitochondrial apoptosis-associated proteins following MPTP opening were also
detected. The results indicated that morin treatment significantly increased cell
viability, decreased LDH activity and cell apoptosis, improved the recovery of
cardiac function and decreased the myocardial infarct size. Furthermore, morin
treatment markedly inhibited MPTP opening, prevented the decrease of DeltaPsim,
and decreased the expression of cytochrome c, apoptotic protease activating
factor-1, caspase-9, caspase-3 and the Bax/Bcl-2 ratio. However, these beneficial
effects were reversed by treatment with atractyloside, an MPTP opener. The
present study demonstrated that morin may prevent MIRI by inhibiting MPTP opening
and revealed the possible mechanism of the cardioprotection of morin and its
acting target. It also provided an important theoretical basis for the research
on drug interventions for MIRI in clinical applications.
PMID- 29956745
TI - Silencing Ubc9 expression suppresses osteosarcoma tumorigenesis and enhances
chemosensitivity to HSV-TK/GCV by regulating connexin 43 SUMOylation.
AB - The ability of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV)
systems to kill tumor cells is partially dependent on the integrity of gap
junction intercellular communication (GJIC) of targeted tumor cells. Recent
studies have suggested that connexin 43 (Cx43), which serves a role in gap
junction-mediated intercellular communication, is regulated by small ubiquitin
like modifiers (SUMOs). However, the roles of these post-translational
modifications remain to be elucidated. The present study demonstrated
overexpression of SUMO-conjugating enzyme Ubc9 (Ubc9) protein in osteosarcoma.
Silencing Ubc9 by siRNA inhibited osteosarcoma cell proliferation and migration,
and significantly increased the sensitivity of cells to HSV-TK/GCV systems both
in vitro and in vivo. Further experimentation demonstrated that silencing Ubc9
induced decoupling of SUMO1 from Cx43, generating increased free Cx43 levels,
which is important for reconstructing GJIC and recovering cellular functions. In
conclusion, the present study revealed a novel method for the effective
restoration of GJIC in osteosarcoma cells, which may increase their sensitivity
to conventional chemotherapy.
PMID- 29956746
TI - Liposomal paclitaxel induces fewer hematopoietic and cardiovascular complications
than bioequivalent doses of Taxol.
AB - Paclitaxel (PTX) exhibits potent antineoplastic activity against various human
malignancies; however, clinical application must overcome the inherent
hydrophobicity of this molecule. The commercialized Taxol formulation utilizes
Cremophor EL (CrEL)/ethanol as a solvent to stabilize and dispense PTX in an
aqueous solution. However, adverse CrEL-induced hypersensitivity reactions have
been reported in ~30% of recipients, and 40% of patients receiving premedication
may also experience this adverse effect. Therefore, the development of a CrEL
free delivery system is crucial, in order to fully exploit the therapeutic
efficacy of PTX. In the present study, a novel liposomal PTX (lipo-PTX)
formulation was optimized with regards to encapsulation rate and long-term
stability, arriving at a molar constituent ratio of soybean
phosphatidylcholine:cholesterol:N-(carbonyl-methoxy-poly-ethylene glycol 2000)
1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt:PTX at 95:2:1:2.
Comparable doses of lipo-PTX and Taxol were bioequivalent in terms of therapeutic
efficacy in xenograft tumor models. However, the systemic side effects, including
hematopoietic toxicity, acute hypersensitivity reactions and cardiac
irregularities, were significantly reduced in lipo-PTX-treated mice compared with
those infused with reference formulations of PTX. In conclusion, the present
study reported that lipo-PTX exhibited a higher therapeutic index than clinical
PTX formulations.
PMID- 29956747
TI - miRNA-145 inhibits myocardial infarction-induced apoptosis through autophagy via
Akt3/mTOR signaling pathway in vitro and in vivo.
AB - The present study investigated the effects of micro (mi)RNA-145 on acute
myocardial infarction (AMI) and the potential underlying mechanism. A total of 6
AMI and 6 normal rat tissues were investigated for the present study. It was
demonstrated that miRNA-145 expression was downregulated in the AMI rat model,
compared with the control group. Downregulation of miRNA-145 increased cardiac
cell apoptosis, suppressed phosphorylated (p)-RAC-gamma serine/threonine-protein
kinase (Akt3) and p-mechanistic target of rapamycin (mTOR) protein expression
levels and suppressed autophagy in an in vitro model of AMI. However,
overexpression of miRNA-145 decreased cardiac cell apoptosis, induced p-Akt3 and
p-mTOR protein expression and promoted autophagy in the in vitro model of AMI.
The inhibition of Akt3 (GSK2110183, 1 nM) decreased the effect of the miRNA-145
upregulation on cell apoptosis in the in vitro model of AMI. Chloroquine
diphosphate (5 uM) inhibited the regulatory effect of miRNA-145 upregulation on
autophagy to adjust cell apoptosis, in the in vitro model of AMI. The results of
the present study demonstrate that miRNA-145 inhibits myocardial infarction
induced apoptosis via autophagy associated with the Akt3/mTOR signaling pathway
in vivo and in vitro.
PMID- 29956748
TI - AQP4-knockout alleviates the lipopolysaccharide-induced inflammatory response in
astrocytes via SPHK1/MAPK/AKT signaling.
AB - To date, aquaporin-4 (AQP4) has been considered as a critical contributor to
neuroinflammation, but little is known about the underlying mechanism. Previous
studies have shown that a critical enzyme involved in the sphingomyelin cycle,
sphingosine kinase 1 (SPHK1), is implicated in inflammatory processes and
contributes to chronic neuroinflammation. The present study investigated the role
of AQP4 in proinflammatory cytokine release from astrocytes, with an emphasis on
the SPHK1/mitogen-activated protein kinase (MAPK)/protein kinase B (AKT) pathway.
Using primary cultures isolated from AQP4+/+ and AQP4-/- embryos, the production
of tumor necrosis factor-alpha (TNF-alpha)/interleukin-6 (IL-6) from astrocytes
challenged by lipopolysaccharide (LPS) was compared. The results showed increased
secretion of TNF-alpha/IL-6 in the two groups following LPS treatment, but a
significantly lower level was observed in the AQP4-/- group compared with that in
the AQP4+/+ group. Although upregulation of SPHK1 was detected in the two
genotypes, only a mild increase in SPHK1 was found in the AQP4-/- genotype. The
phosphorylation of MAPK/AKT was also confirmed to be attenuated in the AQP4-/-
group, suggesting decreased MAPK/AKT signaling over time in AQP4-/- astrocytes.
Overall, the study findings demonstrated that AQP4 deficiency alleviates
proinflammatory cytokine release from astrocytes, in association with the
SPHK1/MAPK/AKT pathway. This data improves our understanding of AQP4 in
neuroinflammatory events, highlighting a novel profile of SPHK1 as a potential
target for the treatment of CNS inflammation.
PMID- 29956749
TI - Modulation of the tumor microenvironment by intratumoral administration of IMO
2125, a novel TLR9 agonist, for cancer immunotherapy.
AB - The objective of cancer immunotherapy is to prime the host's immune system to
recognize and attack malignant tumor cells. IMO-2125, a Toll-like receptor 9
(TLR9) agonist, exhibited potent antitumor effects in the murine syngeneic A20
lymphoma and the CT26 colon carcinoma models. IMO-2125 exhibited superior A20
antitumor activity when injected intratumorally (i.t.) compared with equivalent
subcutaneous doses. In mice bearing dual CT26 grafts, the i.t. injection of right
flank tumors elicited infiltration of cluster of differentiation (CD)3+ T
lymphocytes into tumors, resulting in the regression of injected and uninjected
left flank tumors. Depletion of CD8+, but not CD4+, T-cells abrogated the IMO
2125-mediated antitumor response, suggesting that CD8+ lymphocytes are required
for the antitumor activity. In mice harboring right flank CT26 and left flank
beta-galactosidase (beta-gal)-expressing CT26.CL25 grafts, the i.t.
administration of IMO-2125 to the CT26 graft resulted in potent and dose
dependent antitumor activity against the two grafts. Splenic T-cells isolated
from these mice responded to AH1 antigen (present in the two tumors) and beta-gal
antigen (present only in CT26.CL25) in an interferon gamma enzyme-linked
immunospot assay, suggesting the clonal expansion of T-cells directed against
antigens from the two tumors. Mice with ablated CT26 tumors by previous IMO-2125
treatment rejected re-implanted CT26 tumor cells, but not A20 tumor cells,
demonstrating that the initial IMO-2125 treatment created a long-lived tumor
specific immune memory of CT26 antigens. A quantitative increase in CD3+ T
lymphocytes in injected A20 tumors and an upregulation of selected checkpoint
genes, including indoleamine 2,3-dioxygenase (IDO)-1, IDO-2, programmed cell
death protein-1 (PD-1); programmed cell death protein ligand 1 (PD-L1),
carcinoembryonic antigen-related cell adhesion molecule 1, tumor necrosis factor
receptor superfamily member 4 (OX40), OX40 ligand, T-cell immunoglobulin and
mucin-domain-containing 3 protein, lymphocyte-activation gene 3, cytotoxic T
lymphocyte-associated protein 4, were observed following IMO-2125 treatment. IMO
2125 also increased immune checkpoint gene expression in injected and uninjected
contralateral CT26 tumors, suggesting that the co-administration of anti-CTLA-4,
anti-PD-1 or anti-PD-L1 therapies with IMO-2125 may provide additional
therapeutic efficacy.
PMID- 29956750
TI - Long non-coding RNA 00152 functions as a competing endogenous RNA to regulate
NRP1 expression by sponging with miRNA-206 in colorectal cancer.
AB - Colorectal cancer (CRC) is the third most common type of cancer; however, the
molecular mechanisms underlying colorectal tumor metastasis and growth remain
elusive. Recently, accumulating evidence has indicated that long non-coding RNAs
(lncRNAs) play a critical role in CRC progression and metastasis; however, the
biological role and clinical significance of lncRNA 00152 (lnc00152) in CRC
remains largely unknown. Thus, in this study, lnc00152 expression was measured in
80 human CRC tissue samples, 40 non-cancerous tissue samples, and 3 CRC cell
lines (SW480, SW620 and LoVo) using RT-qPCR. We examined the effects of lnc00152
on CRC cells following transfection with lnc00152 overexpression plasmid or
respective siRNA in vitro and in vivo. Luciferase assays revealed the mechanism
driving competitive endogenous RNA (ceRNA). We identified that lnc00152 was
aberrantly overexpressed in colorectal tumors and cancer cells and that lnc00152
was modulated by miRNA-206. lnc00152 overexpression enhanced the proliferative
and invasive ability of CRC cells in vitro, promoted tumor growth in vivo, and
was associated with the shorter overall survival of patients with CRC. In
addition, lnc00152 overexpression promoted epithelial-mesenchymal transition
(EMT) and increased neuropilin-1 (NRP1) expression in the CRC cells. By contrast,
lnc00152 silencing exerted a counteractive effect. Collectively, these findings
demonstrate the critical role of lnc00152 in tumor growth and progression in CRC,
and identify a novel therapeutic target associated with CRC development and
progression.
PMID- 29956751
TI - Psoriasin overexpression confers drug resistance to cisplatin by activating ERK
in gastric cancer.
AB - Psoriasin, a member of the S100 multigenic family, which is aberrantly expressed
in a variety of human tumors, is considered as an attractive molecular target for
cancer treatment. The present study aimed to characterize the role of psoriasin
in gastric cancer (GC), the associated pathways through which it contributes to
cancer development and progression, and the effect of psoriasin on cellular
response to pre-operative chemotherapy in patients with GC. Expression of
psoriasin mRNA and protein were analyzed using quantitative polymerase chain
reaction and immunohistochemistry of gastric cancer cohorts, respectively.
Gastric cancer cell models with differential expression of psoriasin were
generated using stable cell lines that overexpressed psoriasin. The in vitro
biological functions of the cells in response to psoriasin overexpression and to
chemotherapeutic agents were assessed using various cell-based assays. Psoriasin
was overexpressed in patients with advanced GC, and high psoriasin levels led to
poor clinical outcomes. Increasing psoriasin expression in GC cell lines promoted
cell proliferation, migration and invasion in vitro. Furthermore, psoriasin
overexpression caused alterations in the levels of epithelial-mesenchymal
transition-associated proteins, and activated the extracellular signal-regulated
kinase signaling pathway. Additionally, higher levels of psoriasin expression
were significantly associated a lack of response to neoadjuvant chemotherapy in
patients with GC. Psoriasin overexpression tended to decrease the sensitivity of
GC cells to cisplatin, potentially by inhibiting apoptosis or increasing the S
phase population. Taken together, these results indicate that psoriasin may be a
promising therapeutic target for GC treatment, and a potential molecular marker
to predict patient response to pre-operative chemotherapy.
PMID- 29956752
TI - MicroRNA-326 inhibits endometrial fibrosis by regulating TGF-beta1/Smad3 pathway
in intrauterine adhesions.
AB - Intrauterine adhesion (IUA), characterized by endometrial fibrosis, may lead to
infertility and recurrent pregnancy loss. At present, there is no ideal therapy
for IUA. Recent findings have revealed that microRNAs (miRNAs) have a decisive
role in the regulation of fibrosis. The aim of the present study was to
investigate the molecular mechanism of miRNAs in endometrial fibrosis. The
present study compared the expression profiles of miRNAs between endometrial
tissues from patients with IUA and normal endometrial tissues using microarray
analysis. Validation of miR-326 level in endometrial tissues was performed using
reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
Subsequently, the effects of miR-326 on fibrotic markers including alpha-smooth
muscle actin (alpha-SMA), collagen type I alpha 1 chain (COL1A1), transforming
growth factor-beta1 (TGF-beta1) and fibronectin (FN), were evaluated in
endometrial tissues and endometrial stromal cells (ESCs) from patients with IUA.
Additional bioinformatics analysis, luciferase reporter assays, RT-qPCR and
western blotting were performed to identify target genes. Additionally, the
expression levels of TGF-beta1, p-Smad3 and Smad3 were quantified to determine
whether the anti-fibrotic role of miR-326 was associated with the activity of the
TGF-beta1/Smad3 signaling pathway. The present study determined that miR-326 was
downregulated in endometrial tissues from patients with IUA and miR-326 levels
were inversely correlated with the expression of TGF-beta1, alpha-SMA, COL1A1 and
FN. Additional findings revealed that overexpression of miR-326 inhibited
endometrial fibrosis by downregulating these pro-fibrotic genes. TGF-beta1, an
important pro-fibrogenic mediator, was identified as a direct target of miR-326.
Additionally, overexpression of miR-326 blocked the activation of the TGF
beta1/SMAD family member 3 (Smad3) signaling pathway by suppressing the
expression of TGF-beta1 in ESCs from patients with IUA. The findings of the
present study indicated that miR-326 inhibited endometrial fibrosis by
suppressing the TGF-beta1/Smad3 signaling pathway, suggesting that miR-326 may be
a prognostic biomarker and therapeutic target for IUA.
PMID- 29956753
TI - Tristetraprolin activation by resveratrol inhibits the proliferation and
metastasis of colorectal cancer cells.
AB - Resveratrol (RSV) is a polyphenolic compound that naturally occurs in grapes,
peanuts and berries. Considerable research has been conducted to determine the
benefits of RSV against various human cancer types. Tristetraprolin (TTP) is an
AU-rich element-binding protein that regulates mRNA stability and has decreased
expression in human cancer. The present study investigated the biological effect
of RSV on TTP gene regulation in colon cancer cells. RSV inhibited the
proliferation and invasion/metastasis of HCT116 and SNU81 colon cancer cells.
Furthermore, RSV induced a dose-dependent increase in TTP expression in HCT116
and SNU81 cells. The microarray experiment revealed that RSV significantly
increased TTP expression by downregulating E2F transcription factor 1 (E2F1), a
downstream target gene of TTP and regulated genes associated with inflammation,
cell proliferation, cell death, angiogenesis and metastasis. Although TTP
silencing inhibited TTP mRNA expression, the expression was subsequently restored
by RSV. Small interfering RNA-induced TTP inhibition attenuated the effects of
RSV on cell growth. In addition, RSV induced the mRNA-decaying activity of TTP
and inhibited the relative luciferase activity of baculoviral IAP repeat
containing 3 (cIAP2), large tumor suppressor kinase 2 (LATS2), E2F1, and lin-28
homolog A (Lin28) in HCT116 and SNU81 cells. Therefore, RSV enhanced the
inhibitory activity of TTP in HCT116 and SNU81 cells by negatively regulating
cIAP2, E2F1, LATS2, and Lin28 expression. In conclusion, RSV suppressed the
proliferation and invasion/metastasis of colon cancer cells by activating TTP.
PMID- 29956754
TI - Urinary C-X-C motif chemokine 13 is a noninvasive biomarker of antibody-mediated
renal allograft rejection.
AB - Noninvasive monitoring methods of immune status are preferred by transplant
recipients. The present study investigated whether urinary C-X-C motif chemokine
13 (CXCL13) had the potential to reflect ongoing immune processes within renal
allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a
total of 146 renal allograft recipients and 40 healthy controls at scheduled
intervals and at the time of the indicated or protocol biopsy. The results of the
present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal
transplants compared with in those with acute tubular necrosis (ATN; P=0.001),
chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001),
which was associated with a good diagnostic performance for AR [area under the
curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients
with AR were also higher than that of patients with graft dysfunction but no
rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished
between acute antibody-mediated rejection (ABMR) and acute cellular rejection,
with an AUC of 0.856. Furthermore, patients with steroid-resistant AR exhibited
significantly increased urinary CXCL13/Cr levels than patients with reversible AR
(P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first
month of transplant were predictive of graft function at 3 and 6 months (P=0.044
and P=0.04, respectively). Collectively, the findings of the present study
indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable
for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr
levels predicted a poor response to steroid treatment and compromised graft
function.
PMID- 29956755
TI - MicroRNA expression profiles identify biomarkers for predicting the response to
chemoradiotherapy in rectal cancer.
AB - Neoadjuvant chemoradiotherapy (nCRT) following surgery significantly improves the
survival rate of patients with rectal cancer. However, nCRT is associated with
significant adverse symptoms and high medical costs. Therefore, it is important
to investigate potential biomarkers for the prediction of the response to nCRT in
patients with rectal cancer. The present study identified candidate biomarkers
for predicting a complete response (CR) to nCRT in patients with rectal cancer
and investigated the associated mechanisms. Microarray data (accession no.
GSE29298) was downloaded from the Gene Expression Omnibus database.
Differentially expressed microRNAs (miRNAs/miR) were screened between the
pathological CR (pCR) group and no pCR (incomplete response) group. miRNA target
genes were predicted using the miRWalk 2.0 online tool and subjected to Kyoto
Encyclopedia of Genes and Genomes pathway enrichment analysis. Furthermore, a
miRNA co-regulatory network was constructed and disease-associated genes were
predicted. The results demonstrated that a total of 36 upregulated and 5
downregulated miRNAs were identified between the two groups. Among these
differentially expressed miRNAs, miR-548c-5p, miR-548d-5p and miR-663a were
significantly associated with a CR to nCRT. The co-regulatory network and pathway
analysis indicated that miR-548c-5p and miR-548d-5p may function together through
stem cell pluripotency and ubiquitin-mediated proteolysis signaling pathways.
Furthermore, the prediction of disease-associated genes demonstrated that miR
548c-5p/miR-548d-5p and miR-663a may regulate genes associated with rectal
cancer, including mutated in colorectal cancers (MCC) and adenomatous polyposis
coli (APC), and colorectal neoplasms, including interleukin-6 signal transducer
(IL6ST), cell cycle checkpoint kinase 2 (CHEK2), marker of proliferation Ki-67
(MKI67), cadherin 7 (CDH7), calreticulin (CALR) and transforming growth factor
beta1 (TGFB1). Therefore, miR-548c-5p, miR-548d-5p and miR-663a are promising
candidate biomarkers for predicting a CR to nCRT. miR-548c-5p/miR-548d-5p may be
associated with a CR by regulating IL6ST, CHEK2, MKI67 and MCC. In addition, it
may function through the pluripotency of stem cells and ubiquitin-mediated
proteolysis signaling pathways. miR-663a may be associated with a CR to nCRT by
targeting CDH7, CALR, APC and TGFbeta1. Thus, the miRNA biomarkers investigated
in the present study may represent novel therapeutic targets for the prediction
and eventual improvement of the response to nCRT in patients with rectal cancer.
PMID- 29956756
TI - ZIC1 acts a tumor suppressor in breast cancer by targeting survivin.
AB - In this study, we aimed to identify the tumor suppressive roles of zinc finger of
the cerebellum 1 (ZIC1) in patients with malignant breast neoplasms and to
examine the association between ZIC1 and survivin expression. For this purpose,
140 invasive breast cancer specimens, 1,075 RNA breast cancer samples from The
Cancer Genome Atlas (TCGA), 6 human breast cancer cell lines and MCF-10A normal
breast epithelial cells were selected in order to compare the expression level of
ZIC1 with that of survivin via immunohistochemistry and western blot analysis.
Subsequently, the MDA-MB-231 and SK-BR3 cells with a lower ZIC1 expression were
transfected with rLV-Zic1-PGK-Puro lentivirus or rLV-ZsGreen-PGK-Puro lentivirus
in order to observe any alterations in cell proliferation and apoptosis through
MTT assay, colony formation assay, mitochondrial membrane potential assay and
flow cytometric analysis, and to analyze the modulation of molecular mechanisms
by western blot analysis. In addition, xenograft mouse models were constructed to
explore the role of ZIC1 in the growth of implanted tumors. The results revealed
that ZIC1 negatively correlated with survivin in tumors and cells, and a higher
ZIC1 RNA expression indicated a better overall survival in the 1,075 TCGA RNA
breast cancer samples. In vitro, the overexpression of ZIC1 inhibited cell
proliferation, reduced mitochondrial membrane potential and promoted the
apoptosis of the MDA-MB-231 and SK-BR3 breast cancer cells by inactivating the
Akt/mTOR/P70S6K pathway, suppressing survivin expression, modulating the cell
cycle, releasing cytochrome c (Cyto-c) into the cytosol and activating caspase
proteins. In vivo, an elevated ZIC1 expression suppressed the growth of implanted
tumors and downregulated survivin expression in tumors. On the whole, the
findings of this study demonstrate that ZIC1 plays a tumor suppressive role in
breast cancer, by targeting surviving, significantly downregulating its
expression.
PMID- 29956758
TI - [Corrigendum] Differences in atrial fibrillation-associated proteins between the
left and right atrial appendages from patients with rheumatic mitral valve
disease: A comparative proteomic analysis.
AB - Subsequently to the publication of this article, the authors have realized that
an address affiliation associated with certain of the authors had been omitted.
The authors' affiliation information should have appeared as follows (the omitted
address affiliation is featured in bold): Hai Liu1-3*, Guangxian Chen1,2*,
Hongsheng Zheng4*, Han Qin1,2, Mengya Liang1,2, Kangni Feng1,2 and Zhongkai Wu1,2
1Second Department of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen
University; 2Key Laboratory on Assisted Circulation, Ministry of Health,
Guangzhou, Guangdong 510080; 3Third Department of Cardiac Surgery, First
Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052; 4Department
of Cardiac Surgery, Henan Provincial Chest Hospital, Zhengzhou, Henan 450008,
P.R. China. *Contributed equally. The authors regret this error in the
affiliations, and apologize for any inconvenience caused. [the original article
was published in the Molecular Medicine Reports 14: 4232-4242, 2016; DOI:
10.3892/mmr.2016.5776].
PMID- 29956757
TI - lncRNA-ATB functions as a competing endogenous RNA to promote YAP1 by sponging
miR-590-5p in malignant melanoma.
AB - The critical long non-coding RNAs (lncRNAs) involved in the carcinogenesis and
progression of malignant melanoma (MM) have not been fully investigated. In the
present study, it was identified that lncRNA activated by transforming growth
factor-beta (lncRNA-ATB) was upregulated in MM tissues and cells compared with
benign nevus cells and human melanocytes, via comparative lncRNA screening from
Gene Expression Omnibus datasets and reverse transcription-quantitative
polymerase chain reaction analysis. Furthermore, lncRNA-ATB promoted the cell
proliferation, cell migration, and cell invasion of MM cells in vitro, and tumor
growth in vivo. It was additionally identified that lncRNA-ATB attenuated cell
cycle arrest and inhibited cellular apoptosis in MM cells. Finally, it was
demonstrated that lncRNA-ATB functions as a competing endogenous RNA (ceRNA) to
enhance Yes associated protein 1 expression by competitively sponging microRNA
miR-590-5p in MM cells. In conclusion, the present study revealed the expression
and roles of lncRNA-ATB in MM, and indicated that lncRNA-ATB functions as a ceRNA
to promote MM proliferation and invasion by sponging miR-590-5p.
PMID- 29956759
TI - Embelin inhibits abdominal aortic aneurysm through decreasing IL-6-induced STAT3
and NF-kappaB inactivation.
AB - The aim of the present study was to investigate the effect of embelin on
abdominal aortic aneurysm (AAA). AAA model mice were induced by chronic infusion
of 1,000 ng/kg/min Angiotensin II. AAA model mice were treated with 25, 50 or 100
mg/kg embelin for 28 days. Embelin inhibited tumor necrosis factor-alpha,
interleukin (IL)-1beta, IL-6, IL-18 and malondialdehyde (MDA) level activities,
increased superoxide dismutase, glutathione (GSH) and GSH peroxidase level
activities and inhibited MDA level activities in AAA mice Embelin suppressed the
secretion of matrix metalloproteinase-9 protein expression, monocyte
chemoattractant protein-2 activity and epithelial neutrophil-activating peptide
expression levels in AAA mice. Embelin suppressed phosphorylated-signal
transducer and activator of transcription (STAT) 3, phosphorylated-p38 mitogen
activated protein kinase and nuclear factor (NF)-kappaB protein expression in AAA
mice. These findings indicate that embelin inhibits AAA through decreasing IL-6
induced STAT3, and NF-kappaB inactivation.
PMID- 29956760
TI - Identification of a noncoding RNA-mediated gene pair-based regulatory module in
Alzheimer's disease.
AB - Alzheimer's disease (AD) is the most common type of neurological disorder that
results from brain cell death; however, not all brain regions are simultaneously
affected to the same extent. Despite single biomarkers for AD having been
determined on a genome-wide scale, the differential co-expression in gene pairs
between regions and interactions with other types of cellular molecules,
particularly non-coding (nc)RNAs, are often overlooked in studies investigating
the underlying mechanisms associated with AD. In the present study, based on
1,548 samples obtained from a cohort of 90 patients with AD spanning 19 brain
regions, a gene-pair based method was established for the classification of 19
brain regions into seven different groups, including marked disparate groupings
of six single regions and a cluster of another 13 regions as revealed by
principal component analysis (PCA). To further investigate the different
underlying mechanisms associated with each group, five highly interconnected
functional modules of the protein-protein interaction network were demonstrated
to characterize the seven region groups containing six single groups and 13
clustered regions based on 4,731 gene-pairs. Genes in two of the functional
modules exhibited a strong association with pathways associated with the nervous
system, including cholinergic synapses, circadian entrainment and dopaminergic
synapses. Notably, following integration of these two modules with a ncRNA
mediated network, one module demonstrated a strong association with micro
(mi)RNAs, which were revealed to interact with numerous long non-coding (lnc)RNAs
associated with AD, such as metastasis associated lung adenocarcinoma transcript
1 and taurine upregulated 1. This suggested that mRNAs and lncRNAs may represent
competing endogenous RNAs for binding with miRNAs. Thus, these results indicated
that the ncRNA-mediated gene regulatory module detected by the established gene
pair-based method may further the understanding of underlying mechanisms
associated with AD as well as aid the development of novel therapeutic strategies
for the treatment of patients with AD.
PMID- 29956761
TI - Aclidinium bromide inhibits the growth and metastasis of gastric cancer MKN-28
cells via the PI3K signaling pathway.
AB - The present study investigated the effect and underling mechanisms of aclidinium
bromide, a novel, inhaled long-acting muscarinic antagonist, on the development
of gastric cancer. Human gastric cancer MKN-28 cells, as a model in vitro, were
treated with aclidinium bromide and dimethyl sulfoxide. Cell Counting Kit-8
assay, transwell assay and flow cytometry were used to assess cell proliferation,
invasion/migration and apoptosis, respectively. In addition, western blotting was
performed to determine the relative expression of proteins associated with
apoptosis and the phosphatidylinositol-3-kinase (PI3K) signaling pathway. Optical
density values of MKN-28 cells were decreased in a time- and dose-dependent
manner in the aclidinium bromide treated group. Matrigel invasion analysis
demonstrated the number of invasive cells were significantly decreased in the
aclidinium bromide-treated group when compared with the control group.
Furthermore, aclidinium bromide led to the marked reduction of the number of MKN
28 cells passing though the microwells of the transwell chamber. The expression
levels of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) decreased, and the
expression of pro-apoptotic proteins active Caspase3 and Bcl-2-associated X
protein increased concurrently following aclidinium bromide stimulation using
western blotting. The phosphorylation of protein kinase B and mechanistic target
of rapamycin were significantly inhibited in MKN-28 cells treated with aclidinium
bromide; and the activity of the downstream proteins such as p70S6K and Cyclin D1
were also significantly decreased. In conclusion, aclidinium bromide could
inhibit gastric cancer cell proliferation and metastasis, which may be associated
with the enhancement of apoptosis induced by the PI3K signaling pathway.
PMID- 29956763
TI - Polymorphism rs7521584 in miR-429 is associated with the severity of atrophic
gastritis in patients with Helicobacter pylori infection.
AB - The aim of the present study was to investigate an association of genetic
polymorphism (rs7521584) located in miR-200a-200b-429 cluster, which has tumor
suppressor and pro-inflammatory function, with the development of gastric mucosal
atrophy and metaplasia as a pre-malignant condition. Gastric mucosa samples were
obtained from the antrum of 393 patients with no malignancies. The rs7521584
genotype was determined using the polymerase chain reaction-single-strand
conformation polymorphism analysis method. The degree of gastritis was assessed
histologically in all subjects and serum levels of pepsinogen (PG) I/II were
quantified in 123 out of 393 patients. Patients with an atrophy score >=1 and
metaplasia score >=1 were classified into the atrophic gastritis group (AG
group). The rs7521584 TT genotype was significantly associated with the
development of atrophic gastritis [odds ratio (OR), 2.41; 95% confidence interval
(CI), 1.10-5.25; P=0.027), particularly in patients with H. pylori infection (OR,
3.31; 95% CI, 1.35-8.12; P=0.0089). In addition, in patients younger than 60
years of age, this genotype was associated with atrophic gastritis (OR, 3.15; 95%
CI 1.03-9.61; P=0.044)]. In patients with H. pylori infection, the metaplasia
score was significantly higher in the TT homozygote compared with the GG+GT
genotype. In the rs7521584 TT homozygote, serum PG I/II ratio was significantly
reduced with increasing age (P=0.0084). No significant trend was identified
between the GG+GT genotype and age. The results of the current study indicated
that the rs7521584 minor allele homozygote was associated with the development of
chronic gastritis under the influence of H. pylori-induced inflammation,
particularly with the severity of metaplastic alterations.
PMID- 29956762
TI - Recombinant club cell protein 16 (CC16) ameliorates cigarette smoke-induced lung
inflammation in a murine disease model of COPD.
AB - Club cell protein (CC16) is expressed primarily by club cells possesses anti
inflammatory properties and is located in the bronchiolar epithelium. Previous
studies have demonstrated that CC16 deficiency is associated with the progression
of chronic obstructive pulmonary disease (COPD). In the present study, the
therapeutic effects of recombinant rat CC16 protein in mice with COPD were
examined and the underlying mechanisms investigated. A total of 30 adult male
C57/BL6 mice were randomly divided into three groups (10 mice/group). A mouse
COPD model was generated by exposing 20 mice to cigarette smoke (CS) for 24
weeks. A total of 10 mice were treated intranasally with rCC16 (2.5 ug/g body
weight) and control mice were exposed to normal room air. Results indicated that
rCC16 treatment ameliorated pathological damage in the lungs and reduced the
production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8,
which were induced by CS exposure. After rCC16 administration, endogenous CC16
was upregulated and the body weight of COPD mice was increased, whereas the
opposite was observed in CS-exposed mice. Additionally, rCC16 treatment inhibited
the DNA binding of NF-kappaB/p65 in lung tissues and reduced nuclear
translocation of NF-kappaB/p65 in BALF and epithelial cells. Moreover, rCC16
treatment lead to a decrease in the total number of BALF cells, including
macrophages, which was elevated in COPD mice. In conclusion, the present results
demonstrate that rCC16 has therapeutic effects on COPD by downregulating pro
inflammatory factors via the NF-kappaB pathway.
PMID- 29956764
TI - Protective effect of KLF15 on vascular endothelial dysfunction induced by TNF
alpha.
AB - Atherosclerosis (AS) is a cardiovascular disease with a relatively high incidence
rate. Kruppel-like factor 15 (KLF15) has a role in numerous pathological
processes, including nephropathy, abnormal glucose metabolism and myocardial
injury. The aim of the present study was to investigate the function of KLF15 in
vascular endothelial dysfunction. MTT analyses, nitric oxide (NO) detection and
cell adhesion detection kits were used to investigate the viability and adhesion
of, and quantity of NO released by Eahy926 cells induced by tumor necrosis factor
(TNF)-alpha, respectively. Reverse transcription-quantitative polymerase chain
reaction and western blot analyses were performed to determine the expression
levels of KLF15, endothelial nitric oxide synthase, monocyte chemoattractant
protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), transforming
growth factor-beta1 (TGF-beta1), phosphorylated (p-)transcription factor p65
(p65) and nuclear factor erythroid 2-related factor 2 (Nrf2). The results of the
present study demonstrated that TNF-alpha was able to induce vascular endothelial
dysfunction in Eahy926 cells at an optimum concentration of 10 ng/ml.
Overexpression of KLF15 markedly enhanced cell viability in addition to the
quantity of released NO of TNF-alpha-induced Eahy926 cells, and increased the
expression levels of eNOS and Nrf2. Furthermore, overexpression of KLF15 markedly
suppressed the rate of cellular adhesion, and downregulated levels of MCP-1, ICAM
1, TGF-beta1 and p-p65 in TNF-alpha induced Eahy926 cells. In conclusion, the
results of the present study suggested that overexpression of KLF15 in Eahy926
cells exhibited a protective effect against TNF-alpha induced dysfunction via
activation of Nrf2 signaling and inhibition of nuclear factor kappaB signaling.
PMID- 29956765
TI - Application of 460 nm visible light for the elimination of Candida albicans in
vitro and in vivo.
AB - The aim of the present study was to investigate the eradicating effects of 460 nm
blue light (BL) on Candida albicans in vitro and in C. albicans-infected skin
wounds in a mouse model. In the present study, the antifungal effects of
irradiation with BL on C. albicans in vitro and in vivo were investigated. C.
albicans colonies and cell numbers were investigated using the spread plate
method and flow cytometry respectively following treatment with BL irradiation.
In order to determine whether BL can eradicate C. albicans cells within biofilms,
an in vitro C. albicans biofilm model was established, and the effect of BL was
subsequently investigated using a confocal laser scanning microscope and a
Live/Dead staining kit. Furthermore, a mouse skin wound infection model infected
with C. albicans was established. Wound healing rates and histological
examinations were determined 0, 3, 7, 10 and 14 days post-wounding. The results
revealed that C. albicans was eradicated by BL in a dose-dependent manner, with a
minimum fluence of 60 J/cm2. Irradiation with BL almost completely eradicated C.
albicans when the light fluence was 240 J/cm2. C. albicans inside biofilms was
also eradicated and biofilms were destroyed following BL irradiation at 240
J/cm2. In addition, BL was revealed to significantly suppress C. albicans
infection in vivo. Irradiation with BL promoted the wound healing of C. albicans
infected-skin wounds in a mouse model. In conclusion, the results of the present
study demonstrated that 460 nm BL may eradicate planktonic and biofilm C.
albicans in vitro, and represents a novel therapeutic strategy for the treatment
of C. albicans infections in vivo.
PMID- 29956766
TI - CNOT1 is involved in TTP-mediated ICAM-1 and IL-8 mRNA decay.
AB - Subunit 1 is the scaffold protein of the carbon catabolite repressor protein 4
(CCR4)-negative on TATA (NOT) complex (CNOT1). In our previous study, it was
reported that tristetraprolin (TTP) could recruit subunit 7 of the CCR4-NOT
complex (CNOT7) to induce the degradation of intercellular adhesion molecule-1
(ICAM-1) and interleukin-8 (IL-8) mRNA in human pulmonary microvascular
endothelial cells (HPMECs). It was additionally demonstrated that TTP, CNOT7 and
CNOT1 formed a complex in HPMECs. However, whether CNOT1 is involved in TTP
mediated ICAM-1 and IL-8 mRNA decay remains unclear. The present study
demonstrated that CNOT1 knockdown improved ICAM-1 and IL-8 mRNA stabilization and
protein expression levels. The immunofluorescence results demonstrated that
CNOT1, CNOT7 and TTP are co-localized in the cytoplasm. CNOT1 silencing abolished
CNOT7 and TTP coimmunoprecipitation. However, CNOT7 silencing did not influence
CNOT1 and TTP coimmunoprecipitation, and TTP silencing additionally did not
influence CNOT1 and CNOT7 coimmunoprecipitation. These results together with the
authors' previous study, have identified that CNOT1 provides a platform for the
recruitment of TTP and CNOT7, and is involved in TTP-mediated ICAM-1 and IL-8
mRNA decay.
PMID- 29956767
TI - Resveratrol improves neurological outcome and neuroinflammation following spinal
cord injury through enhancing autophagy involving the AMPK/mTOR pathway.
AB - Resveratrol, a natural phenolic compound, provides neuroprotective effects,
however, the specific mechanisms of action remain to be elucidated. The purpose
of the present study was to examine the neuroprotective effect of resveratrol on
spinal cord injury (SCI) and the potential molecular mechanisms of action. A rat
model of SCI was induced using Allen's method, and resveratrol (100 mg/kg) was
intraperitoneally injected 1 day following surgery. The recovery of neurological
function was assessed using the Basso, Beattie, Bresnahan scoring system and an
inclined plane test. The concentrations of pro- and anti-inflammatory factors
were measured using ELISA. The expression and location of autophagy markers were
measured using western blot and immunofluorescence analyses. The results
suggested that resveratrol administration resulted in functional improvement of
locomotor activity and reduced neuroinflammation following the induction of SCI.
In addition, autophagy was activated following SCI, as demonstrated by the
significantly increased ratio of microtubule-associated protein light chain 3
(LC3)-II/LC3-I and expression of Beclin-1 in the injured spinal cord. Of note,
the enhancement of phosphorylated (p)-AMP-activated protein kinase (AMPK) and the
reduction of p-mammalian target of rapamycin (mTOR) following SCI indicated that
the SCI-induced activation of autophagy was associated with the AMPK/mTOR
signaling pathway. Resveratrol treatment further enhanced the activation of
autophagy via the AMPK/mTOR pathway following SCI. By contrast, the autophagic
inhibitor, 3-methyladenine, partially inhibited the neuroprotective effects of
resveratrol treatment. Together, these findings suggested that resveratrol
promoted functional recovery and inhibited neuroinflammation through the
activation of autophagy mediated by the AMPK/mTOR pathway following SCI.
PMID- 29956768
TI - JAG1 loss-of-function mutations contributed to Alagille syndrome in two Chinese
families.
AB - Alagille syndrome (ALGS) is primarily caused by jagged1 (JAG1) mutations, 70% of
which are protein-truncating mutations. However, no mutation hotspots have been
discovered, and the pathogenic mechanism is not fully understood. The aim of the
present study was to analyze two protein-truncating JAG1 mutations detected in
three Chinese ALGS patients. Mutation c.1261delT (p.Cys421Valfs) was identified
in one patient with hepatic damage, xanthomas, facial abnormalities and
cardiovascular defects, which was inherited from his father. The other mutation,
c.1382_1383delAC (p.Asp461Glyfs), carried by a pair of monozygotic twins with
hepatic damage, facial abnormalities and cardiovascular defects, was de novo.
Biological experiments were performed to study the characteristics and function
of these mutations. The p.Cys421Valfs and p.Asp461Glyfs mutant proteins appeared
to be truncated in western blotting using anti-Flag bound to the N-terminus of
JAG1. The RBP-Jkappa-responsive reporter gene assay was used to investigate the
ability of mutant JAG1 proteins to activate the Notch signaling pathway. The
mutant proteins had a lower luciferase activity than the wild-type, indicating
impaired transcriptional activation ability. Western blotting using soluble JAG1
from the culture medium revealed that the expression levels of the mutant
proteins were lower than that of the wild-type, suggesting that less mutant JAG1
protein underwent proteolytic cleavage than the wild-type. In conclusion, these
two loss-of-function JAG1 mutations may be associated with ALGS manifestations in
these patients.
PMID- 29956769
TI - Thymosin beta4 promotes endothelial progenitor cell angiogenesis via a vascular
endothelial growth factor-dependent mechanism.
AB - Endothelial progenitor cells (EPCs) are a promising cell source for tissue repair
and regeneration, predominantly through angiogenesis promotion. Paracrine
functions serve a pivotal role in EPC-mediated angiogenesis, which may be
impaired by various cardiovascular risk factors. Therefore, it is important to
identify a solution that optimizes the paracrine function of EPCs. Thymosin beta4
(Tbeta4) is a peptide with the potential to promote tissue regeneration and wound
healing. A previous study demonstrated that Tbeta4 enhances the EPC-mediated
angiogenesis of the ischemic myocardium. In the present study, whether Tbeta4
improved angiogenesis by enhancing the paracrine effects of EPCs was
investigated. A tube formation assay was used to assess the effect of
angiogenesis, and the paracrine effects were measured using an ELISA kit. The
results indicated that Tbeta4 improved the paracrine effects of EPCs, evidenced
by an increase in the expression of vascular endothelial growth factor (VEGF).
EPC-conditioned medium (EPC-CM) significantly promoted human umbilical vein
endothelial cell angiogenesis in vitro, which was further enhanced by
pretreatment with Tbeta4. The effect of Tbeta4 pretreated EPC-CM on angiogenesis
was abolished by VEGF neutralizing antibody in vitro, indicating that increased
VEGF secretion had a pivotal role in Tbeta4-mediated EPC angiogenesis.
Furthermore, transplantation of EPCs pretreated with Tbeta4 into infarcted rat
hearts resulted in significantly higher VEGF expression in the border zone,
compared with EPC transplantation alone. To further investigate whether the
Akt/eNOS pathway was involved in Tbeta4-induced VEGF secretion in EPCs, the
expression levels of VEGF in EPC-CM were significantly decreased following
knockdown of Akt or eNOS by small interfering RNA transfection. In conclusion,
Tbeta4 significantly increased angiogenesis by enhancing the paracrine effects of
EPCs, evidenced by the increased expression of VEGF. The RAC-alpha
serine/threonine-protein kinase/endothelial nitric oxide synthase signal
transduction pathway was involved in the regulation of Tbeta4-induced VEGF
secretion in EPCs. Further studies are required to investigate the long-term
prognosis of patients with coronary heart disease following Tbeta4-pretreated EPC
transplantation.
PMID- 29956770
TI - Serum glycine dehydrogenase is associated with increased risk of lung cancer and
promotes malignant transformation by regulating DNA methyltransferases
expression.
AB - Identification of novel risk factors that are critical to the initiation of lung
cancer will be key for its prevention. Recently, it has been reported that
glycine dehydrogenase (GLDC) can drive the formation of lung cancer initiating
cells. However, there have been no perspective studies on the association between
circulating GLDC and lung cancer until now. To identify whether serum GLDC is a
risk factor for lung cancer, the present study conducted a nested case-control
study within a Chinese cohort. Using ELISAs, serum GLDC was measured in 300 case
subjects, who were subsequently diagnosed with lung cancer during follow-up, and
in 600 matched healthy controls. The results revealed that serum GLDC was
associated with increased lung cancer risk [odds ratio=1.48; 95% confidence
intervals (1.01-2.04)]. Spearman correlation was employed to analyze the
associations between age, body mass index, years of smoking and the serum
concentration of GLDC. It was demonstrated that years of smoking was associated
with serum GLDC (spearman's correlation, rho=0.81) in patients with lung cancer.
However, the association was attenuated in the serum of matched controls
(rho=0.48). In addition, overexpression of GLDC protein contributed to malignant
transformation and inhibited microRNA (miR)-29 family expression in normal human
bronchial epithelial (NHBE) cells. Aberrant methylation of tumor suppressive gene
(TSG) is an early event in the development of lung cancer, which is controlled by
DNA methyltransferases (DNMTs). The present study demonstrated that GLDC promoted
the expression of DNMT proteins; however, the miR-29 family inhibited their
expression in NHBE cells. Thus, it was concluded that elevated serum GLDC may
increase lung cancer risk, and that smoking, GLDC, the miR-29 family and DNMT
signaling pathways may serve an important role in early malignant transformation
during the development of lung cancer.
PMID- 29956771
TI - Association study of frameshift and splice variant polymorphisms with risk of
idiopathic recurrent pregnancy loss.
AB - Recurrent pregnancy loss (RPL) is defined as >=2 consecutive pregnancy losses,
and can be caused by various factors, including genetics, chromosomal
abnormalities, thrombophilia, immune disorders, nutritional factors,
environmental factors, psychological stress or maternal infections; however, as
many as 50% of RPL cases are idiopathic. In the present study, the role of
genetic polymorphisms in RPL was investigated. Four gene polymorphisms were
selected by whole exome sequencing, including membrane spanning 4-domains A14
(MS4A14)D>I (rs3217518), solute carrier family 2 member 7 (SLC2A7)D>I
(rs60746313), pregnancy specific beta-1-glycoprotein 9 (PSG9)C>T (rs3746297) and
ATP binding cassette subfamily B member 5 (ABCB5)C>G (rs17143187), and the aim
was to investigate their association with RPL in Korean women. Genotyping was
performed using polymerase chain reaction-restriction fragment length
polymorphism assay. Allele combination analysis revealed that the four-allele
combination I-D-T-G, (MS4A14/SLC2A7/PSG9/ABCB5) was associated with a decreased
risk for RPL. Interaction analysis demonstrated that the following genotypes:
MS4A14 DI+II, SLC2A DI+II and ABCB 5 CG+GG, were associated with a prothrombin
time >=12 sec and with RPL risk. It may be concluded that the four gene
polymorphisms do not affect RPL individually, but are associated with RPL when in
combination with other genes or blood coagulation factors. Notably, the MS4A14 I
allele, with a prothrombin time >=12 sec, may be a potential biomarker for
diagnosis, prevention and prognosis of RPL.
PMID- 29956772
TI - LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by
regulating the miR-4310/LGR5/Wnt/beta-catenin signaling pathway.
AB - Previous studies have indicated that overexpression of long noncoding RNA cancer
susceptibility 15 (CASC15) may promote tumor development and progression in
gastric cancer and hepatocellular carcinoma. However, the function of CASC15 in
colon cancer remains unknown. In the present study, the expression of CASC15 was
upregulated in colon cancer tissues and its expression was correlated with
clinical Tumor-Node-Metastasis stage and tumor metastasis. In addition, knockdown
of CASC15 significantly inhibited the proliferation, migration and invasion of
colon cancer cells in vitro and in vivo. Following mechanistic experiments,
CASC15 was observed to act as a sponge to suppress microRNA (miR)-4310 that
targeted LGR5. Through the inhibition of miR-4310, CASC15 promoted leucine-rich
repeat-containing G-protein coupled receptor 5 (LGR5) expression and consequently
activated the Wnt/beta-catenin signaling pathway. The results revealed that the
inhibition of the Wnt/beta-catenin signaling pathway in CASC15-overexpressing
colon cancer cells suppressed cellular proliferation, migration and invasion.
Collectively, these results demonstrated that CASC15 promoted colon cancer growth
and metastasis through the activation of the Wnt/beta-catenin signaling pathway
in a miR-4310/LGR5 dependent manner. Thus, the present study suggested that
CASC15 may be a therapeutic target for colon cancer treatment.
PMID- 29956773
TI - Protective properties of spliced X box binding protein 1 in ozone-induced spinal
cord neuronal death.
AB - Administration of ozone (O3) is often used in the treatment of low back pain.
Administration of O3 can, however, cause neurotoxicity in spinal cord neurons via
induction of endoplasmic reticulum (ER) calcium (Ca2+) release and activation of
the Ca2+/calmodulin-dependent protein kinase II (CaMKII)/mitogen-activated
protein kinase (MAPK) pathway. The aim of the current study was to confirm
whether administration of O3 causes ER stress and if the consequential
overexpression of adenovirus-mediated spliced X box binding protein 1 (XBP1s),
which is the effector of ER stress and a crucial transcriptional factor gene in
charge of cell survival, has a protective effect on spinal cord neurons after O3
exposure. To address this aim, the expression of GRP78, an ER chaperone and
signaling regulator, and the expression of XBP1s in rat primary spinal cord
neurons that underwent O3 exposure were investigated. Primary neurons exposed to
O3 exhibited increased GRP78 and XBP1s expression levels. Interestingly, the
effect of decreased neuron viability was blocked when cells were pretreated with
Adv-XBP1s. Moreover, overexpression of XBP1s suppressed cell death caused by O3
exposure. These results suggest that overexpression of activated XBP1s protects
against neuronal cell death following O3 exposure and that activation of the
XBP1s pathway may offer a preventative way for prophylactic treatment of spinal
cord neurons exposed to O3.
PMID- 29956774
TI - Whole-exome sequencing analysis of products of conception identifies novel
mutations associated with missed abortion.
AB - Missed abortion (MA) refers to a pregnancy in which there is fetal demise without
outside intervention, and additionally no uterine activity that may expel the
product of conception (POC) prior to 20 weeks of gestation. Chromosomal
abnormalities are the primary cause of MA and single gene defects in the POC may
additionally be associated with MA; however, few studies have been conducted on
the identification of mutations by whole-exome sequencing. In the present study,
19 unrelated MA POCs were collected and whole-exome sequencing was performed on
the POC. Bioinformatics analysis was performed on sequence variants from a list
of 286 selected candidate genes that were associated with early embryonic
lethality and MA. A total of 36 sequence variants in 32 genes potentially
associated with MA were identified in 15 out of 19 patients. Gene Ontology
analysis suggested that these genes were enriched in biological processes in
early embryonic development, including 'chordate embryonic development', 'cell
proliferation' and 'forebrain development'. Further strict in silico
bioinformatics analysis predicted that the LIM domain-binding protein 1
(c.662C>T; p.S221L) variant was a highly pathogenic variant. In conclusion, the
results of the present study provide researchers and clinicians with a better
understanding of the etiology and molecular mechanism of human embryonic
lethality and MA.
PMID- 29956775
TI - Identification of open chromosomal regions and key genes in prostate cancer via
integrated analysis of DNase-seq and RNA-seq data.
AB - Prostate cancer is a type of adenocarcinoma arising from the peripheral zone of
the prostate gland, and metastasized prostate cancer is incurable with the
current available therapies. The present study aimed to identify open chromosomal
regions and differentially expressed genes (DEGs) associated with prostate cancer
development. The DNase sequencing data (GSE33216) and RNA sequencing data
(GSE22260) were downloaded from the Gene Expression Omnibus database. DNase I
hypersensitive sites were detected and analyzed. Subsequently, DEGs were
identified and their potential functions were enriched. Finally, upstream
regulatory elements of DEGs were predicted. In LNCaP cells, following androgen
receptor activation, 244 upregulated and 486 downregulated open chromosomal
regions were identified. However, only 1% of the open chromosomal regions were
dynamically altered. The 41 genes with upregulated open chromosomal signals
within their promoter regions were primarily enriched in biological processes.
Additionally, 211 upregulated and 150 downregulated DEGs were identified in
prostate cancer, including eight transcription factors (TFs). Finally, nine
regulatory elements associated with prostate cancer were predicted. In
particular, inhibitor of DNA binding 1 HLH protein (ID1) was the only
significantly upregulated TF which exhibited motif enrichment in the promoter
regions of upregulated genes. CCCTC-binding factor (CTCF) and ELK1 ETS
transcription factor (ELK1), enriched in the open promoter regions of
downregulated genes, were potential upstream regulatory elements. Furthermore,
reverse transcription-quantitative polymerase chain reaction analysis confirmed
that ID1 expression was significantly upregulated in LNCaP cells and 5alpha
dihydrotestosterone (DHT)-treated LNCaP cells compared with that in BPH1 cells,
while CTCF and ELK1 expression was significantly downregulated in LNCaP cells and
DHT-treated LNCaP cells. In conclusion, ID1, CTCF and ELK1 may be associated with
prostate cancer, and may be potential therapeutic targets for the treatment of
this disease.
PMID- 29956776
TI - Captopril inhibits calpain-mediated apoptosis of myocardial cells in diabetic
rats and improves cardiac function.
AB - To explore the effects of captopril on calpain-mediated apoptosis of myocardial
cells and cardiac function in diabetic rats, 30 adult male Sprague-Dawley rats
were randomly divided into three groups: Negative control (NC group), untreated
diabetic rats (DM group) and diabetic rats treated with captopril (Cap group).
Diabetes was induced by streptozotocin injection. Captopril was intragastrically
administered at a daily dose of 50 mg/kg for 12 weeks; the NC and DM groups
received an equivalent volume of saline. After 12 weeks of treatment, left
ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure
(LVDEP), maximal rate of left ventricular pressure increase (+dp/dtmax), maximal
rate of left ventricular pressure decrease (-dp/dtmax) and left ventricular mass
index (LVMI) were measured. The levels of calpain-1, calpain-2, B-cell lymphoma
(Bcl)-2, Bcl-2 associated protein X (Bax) and total caspase-3 were detected in
cardiac tissue by western blot analysis. The apoptotic index (AI) was assessed
with a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
assay. The ultrastructure of cardiac tissue was determined by transmission
electron microscopy. Compared with the NC group, LVDEP and LVMI were increased,
whereas LVSP, +dp/dtmax and -dp/dtmax were decreased in the DM group. In the Cap
group, LVDEP and LVMI were decreased, whereas LVSP, +dp/dtmax and -dp/dtmax were
increased compared with the DM group. Bcl-2 protein expression was decreased,
whereas the levels of calpain-1, calpain-2, Bax and total caspase-3 protein were
increased in the DM group, compared with the NC group. Cap treatment increased
Bcl-2 protein expression and decreased calpain-1, calpain-2, Bax and total
caspase-3 protein expression compared with the DM group. Additionally, the AI was
increased in the DM group compared with the NC group, and decreased in the Cap
group compared with the DM group. Furthermore, ultrastructural examination
demonstrated that myocardial cell injury was reduced in the Cap group compared
with the DM group. Therefore, captopril improved myocardial structure and
ventricular function, by inhibiting calpain-1 and calpain-2 activation,
increasing Bcl-2 expression, reducing Bax expression and subsequently inhibiting
caspase-3-dependent apoptosis.
PMID- 29956777
TI - The antioxidant, aged garlic extract, exerts cytotoxic effects on wild-type and
multidrug-resistant human cancer cells by altering mitochondrial permeability.
AB - Aged garlic extract (AGE) has been shown to possess therapeutic properties in
cancer; however its mechanisms of action are unclear. In this study, we
demonstrate by MTT assay that AGE exerts an anti-proliferative effect on a panel
of both sensitive and multidrug-resistant (MDR) human cancer cell lines and
enhances the effects of hyperthermia (42C) on M14 melanoma cells. The evaluation
of the mitochondrial activity in whole cancer cells treated with AGE, performed
by cytofluorimetric analysis in the presence of the lipophilic cationic
fluorochrome JC-1, revealed the occurrence of dose-dependent mitochondrial
membrane depolarization. Membrane potential was measured by the TPP+ selective
electrode. In order to shed light on its mechanisms of action, the effects of AGE
on isolated rat liver mitochondria were also examined. In this regard, AGE
induced a mitochondrial membrane hyperpolarization of approximately 15 mV through
a mechanism that was similar to that observed with the ionophores, nigericin or
salinomycin, by activating an exchange between endogenous K+ with exogenous H+.
The prolonged incubation of the mitochondria with AGE induced depolarization and
matrix swelling, indicative of mitochondrial permeability transition induction
that, however, occurs through a different mechanism from the well-known one. In
particular, the transition pore opening induced by AGE was due to the
rearrangement of the mitochondrial membranes following the increased activity of
the K+/H+ exchanger. On the whole, the findings of this study indicate that AGE
exerts cytotoxic effects on cancer cells by altering mitochondrial permeability.
In particular, AGE in the mitochondria activates K+/H+ exchanger, causes
oxidative stress and induces mitochondrial permeability transition (MPT).
PMID- 29956778
TI - Identification of differentially expressed genes associated with asthma in
children based on the bioanalysis of the regulatory network.
AB - Asthma, the most common chronic respiratory tract disease in children, is
characterized by allergy, recurring airway obstruction and bronchospasm. The aim
of the present study was to screen critical differentially expressed genes (DEGs)
involved in asthma in children. Gene expression in different tissues was compared
between asthmatic children and healthy control subjects in order to identify DEGs
associated with asthma. Protein-protein interaction (PPI) networks were
constructed for the DEGs and weighted gene co-expression network analysis methods
were used to further determine the functional modules associated with DEGs in
different tissue samples. In addition, the gene co-expression network was
constructed. Gene Ontology function analysis and pathway analysis were conducted
to identify critical DEGs. The results identified numerous DEGs from the
different tissue samples, including 1,662 DEGs from nasal-epithelium tissue
samples, 572 DEGs from peripheral blood (PB) samples and 146 DEGs from PB
mononuclear cells samples. In the PPI network, F-box only protein 6 (FBXO6),
histone deacetylase 1 (HDAC1) and amyloid beta precursor protein (APP) were hub
genes and served an important role in the process of asthma. In addition,
proliferating cell nuclear antigen (PCNA), integrin alpha-4 (ITGA4), catenin
alpha-1 (CTNNA1), nuclear factor-kappaB1 (NF-kappaB1) and mechanistic target of
rapamycin (MTOR) may be critical DEGs involved in the progression of asthma in
children. These results suggested that FBXO6, HDAC1 and APP may interact with
PCNA, ITGA4, CTNNA1, NF-kappaB1 and mTOR in the progression of asthma in
children.
PMID- 29956779
TI - Effect of survivin downregulation by simvastatin on the growth and invasion of
salivary adenoid cystic carcinoma.
AB - Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, is
been used in the clinic due to its pleiotropic effects, such as breast cancer,
prostate cancer, pancreatic cancer. Simvastatin has recently been demonstrated to
serve a potential role in the prophylaxis and therapeutics of a number of human
cancers. The majority of reports concerning simvastatin treatment in the majority
of human cancers have demonstrated that survivin is significantly decreased as a
result and has been implicated in tumorigenesis. However, only a limited number
of studies have investigated the use of simvastatin for the treatment of salivary
gland adenoid cystic carcinoma (SACC). Therefore, this agent is a candidate for
further investigation. The aim of the present study was to investigate the
effects of simvastatin on the proliferation, invasion and apoptosis of the human
salivary adenoid cystic carcinoma cell line, SACC-83, as well as survivin
expression in the cells. The Cell Counting kit-8 assay results revealed that
simvastatin inhibited the proliferation of SACC-83 cells in a dose-dependent (10
to 50 uM) and time-dependent (24 to 48 h) manner when compared with the untreated
cells. Flow cytometry analysis indicated that simvastatin increased the
percentage of cells in early and late apoptosis. Invasion assays revealed that
simvastatin treatment inhibited the invasiveness of SACC-83 cells in a dose
dependent manner. In addition, simvastatin downregulated survivin expression in
SACC-83 cells. In conclusion, simvastatin significantly inhibited the
proliferation and invasion of SACC-83 cells, induced apoptosis, and reduced the
expression of survivin, which suggests that simvastatin may be a novel target for
SACC therapy.
PMID- 29956780
TI - HBx gene transfection affects the cycle of primary renal tubular epithelial cells
through regulating cyclin expression.
AB - Hepatitis B virus X protein (HBx) has been previously demonstrated to be
associated with the regulation of cell proliferation; however, the exact
mechanisms underlying this effect remain unclear. The present study aimed to
investigate the regulatory mechanism of HBx on the cycle progression of primary
renal tubular epithelial cells. Primary renal tubular epithelial cells of Sprague
Dawley (SD) rats were separated and cultured. The morphology of cultured cells
was characterized by immunohistochemical analysis and the results demonstrated
that primary renal tubular epithelial cells with the expected morphology and
distribution were successfully separated and cultured from SD rats. HBx gene
pcDNA3.1/myc vector and empty vector were constructed and transfected into cells
as HBx and empty groups, respectively. Following transfection, the mRNA and
protein levels of HBx, cyclin A, cyclin D1 and cyclin E in cells were determined
by reverse transcription-quantitative polymerase chain reaction and western blot
analysis, respectively. The results demonstrated that following HBx gene
transfection, the mRNA and protein levels of HBx, cyclin A, cyclin D1 and cyclin
E in cells were significantly upregulated, compared with the empty control group
(P<0.05). Furthermore, cell apoptosis and the cell cycle were evaluated by
Annexin V-fluorescein isothiocyanate/propidium iodide staining and flow
cytometry. HBx gene transfection significantly inhibited the cell apoptosis
(P<0.05), promoted cell cycle progression from the G1 to S phase and arrested the
cell cycle in the S phase. Therefore, the results of the present study indicated
that HBx gene transfection may regulate the apoptosis and cell cycle of primary
renal tubular epithelial cells by affecting the expression of cyclins. The
results of the present study may improve the understanding of pathogenesis
associated with HBV-associated glomerulonephritis, and may also provide insight
and theoretical support for the future design and development of drugs for the
treatment of hepatitis B virus.
PMID- 29956781
TI - Hydrogen-rich solution against myocardial injury and aquaporin expression via the
PI3K/Akt signaling pathway during cardiopulmonary bypass in rats.
AB - Myocardial ischemia, hypoxia and reperfusion injury are induced by aortic
occlusion, cardiac arrest and resuscitation during cardiopulmonary bypass (CPB),
which can severely affect cardiac function. The aim of the present study was to
investigate the effects of hydrogen-rich solution (HRS) and aquaporin (AQP) on
cardiopulmonary bypass (CPB)-induced myocardial injury, and determine the
mechanism of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)
signaling pathway. Sprague Dawley rats were divided into a sham operation group,
a CPB surgery group and a HRS group. A CPB model was established, and the
hemodynamic parameters were determined at the termination of CPB. The myocardial
tissues were observed by hematoxylin and eosin, and Masson staining. The levels
of myocardial injury markers [adult cardiac troponin I (cTnI), lactate
dehydrogenase (LDH), creatine kinase MB (CK-MB) and brain natriuretic peptide
(BNP)], inflammatory factors [interleukin (IL)-1beta, IL-6 and tumor necrosis
factor-alpha (TNF-alpha)] and oxidative stress indicators [superoxide dismutase
(SOD), malondialdehyde (MDA) and myeloperoxidase (MPO)] were determined by ELISA.
Furthermore, H9C2 cells were treated with HRS following hypoxia/reoxygenation.
Cell viability and cell apoptosis were investigated. The expression of apoptosis
regulator Bcl-2 (Bcl-2), apoptosis regulator Bax (Bax), caspase 3, AQP-1, AQP-4,
phosphorylated (p)-Akt, heme oxygenase 1 (HO-1) and nuclear factor erythroid 2
related factor 2 (Nrf2) were investigated using western blotting and quantitative
polymerase chain reaction of tissues and cells. Following CPB, myocardial cell
arrangement was disordered, myocardial injury markers (cTnI, LDH, CK-MB and BNP),
inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and MDA levels were
significantly increased compared with the sham group; whereas the SOD levels were
significantly downregulated following CPB compared with the sham group. HRS
attenuated myocardial injury, reduced the expression levels of cTnI, LDH, CK-MB,
BNP, IL-1beta, IL-6, TNF-alpha, MDA and MPO, and increased SOD release. Levels of
Bcl-2, AQP-1, AQP-4, p-Akt, HO-1 and Nrf2 were significantly increased following
HRS; whereas Bax and caspase-3 expression levels were significantly reduced
following CPB. HRS treatment significantly increased the viability of myocardial
cells, reduced the rate of myocardial cell apoptosis and the release of MDA and
LDH compared with the CPB group. A PI3K inhibitor (LY294002) was revealed to
reverse the protective effect of HRS treatment. HRS was demonstrated to attenuate
CPB-induced myocardial injury, suppress AQP-1 and AQP-4 expression following CPB
treatment and protect myocardial cells via the PI3K/Akt signaling pathway.
PMID- 29956782
TI - C5a aggravates dysfunction of the articular cartilage and synovial fluid in rats
with knee joint immobilization.
AB - Degenerative alterations in articular cartilage are involved in the pathogenesis
of osteoarthritis. The present study aimed to evaluate the role of complement
component 5a (C5a) in osteoarthritic alterations in the articular cartilage and
synovialis via a joint immobilization (IM) rat model. Rats were assigned to three
groups: Control, IM and IM+anti-C5a antibody (IM+anti-C5a) groups. A terminal
deoxynucleotidyl transferase dUTP nick end labeling assay and hematoxylin and
eosin staining were used to evaluate the morphological alterations in the
articular cartilage and synovialis. Reverse transcription-quantitative polymerase
chain reaction (RT-qPCR) analysis, immunohistochemical analysis and western
blotting were used to evaluate C5a expression in the articular cartilage and
synovialis. An ELISA was used to evaluate C5a-induced alterations in interleukin
(IL)-1beta, IL-17A and tumor necrosis factor (TNF)-alpha levels in the serum and
joint fluid. The results demonstrated that knee joint immobilization induced
destruction of knee joint synovial fluid and cartilage in the IM and IM+anti-C5a
antibody groups. Immobilization significantly increased the expression levels of
C5a in serum and joint fluid in the IM group. Immunohistochemistry, western
blotting and RT-qPCR analysis illustrated markedly increased expression of C5a in
the IM group. Immobilization markedly increased the IL-1beta, IL-17A and TNF
alpha expression levels in the serum and joint fluid in the IM group. Anti-C5a
was able to decrease immobilization-induced alterations in morphology and
cytokines compared with the IM group. The expression of C5a was increased in
synoviocytes and joint cartilage in the IM model. Pro-inflammatory cytokines,
including TNF-alpha and IL-1beta were released in the activated synoviocytes via
the induction of C5a, suggesting that C5a serves an important role in joint
inflammatory processes.
PMID- 29956783
TI - Next-generation sequencing-based detection of EGFR, KRAS, BRAF, NRAS, PIK3CA, Her
2 and TP53 mutations in patients with non-small cell lung cancer.
AB - In recent years, the incidence of non-small cell lung cancer (NSCLC) has become
the highest lethal rate of cancer worldwide. Molecular assays of EGFR, KRAS,
BRAF, NRAS, PIK3CA and Her-2 are widely used to guide individualized treatment in
NSCLC patients. Somatic mutations in 112 NSCLC patients, including 7 oncogenic
driver genes, were detected by Iontorrent personal genome machine (PGM). Sanger
sequencing was used to test and verify the results of PGM. Apart from uncommon
mutations of EGFR, 101 NSCLC specimens were tested by droplet digital PCR
(ddPCR). According to NGS results, mutations were detected in EGFR (58/112,
51.79% of tumors), KRAS (10/112, 8.93%), BRAF (2/112, 1.79%), NRAS (2/112,
1.79%), Her-2 (2/112, 1.79%), PIK3CA (6/112, 5.36%) and TP53 (31/112, 27.69%).
There were 27 samples without any somatic mutations in all genes while 24 samples
harboured mutations in two or more genes. A total of 61 samples had one or more
mutations in a single gene. All alterations of 7 genes were presented and the
overall detection rate of NGS and Sanger sequencing was determined to be 51.79%
(58/112) and 37.50% (42/112), respectively (chi2=5.88, P=0.015). Compared with
Sanger sequencing, the total sensitivity and specificity of NGS assays was 95.24%
(40/42) and 77.14% (54/70), respectively. The overall detection rate of NGS and
ddPCR was 45.54% (46/101) and 47.52% (48/101), respectively (chi2=0.000598,
P=0.98). Compared with ddPCR, the overall sensitivity and specificity of NGS
assays was 95.83% (46/48) and 98.11% (52/53), respectively. The findings
indicated that the positive mutation rate of EGFR tested by NGS was significantly
lower than that by Sanger sequencing, but the difference between ddPCR and NGS
was not statistically significant. The high degree of agreement of reportable
variants is proposed in both NGS and ddPCR analysis, suggesting the performance
of NGS assays in routine clinical detection may be useful in determining the
treatment decisions in NSCLC patients.
PMID- 29956784
TI - Antitumor effects of Xi Huang pills on MDA-MB-231 cells in vitro and in vivo.
AB - The management of patients with triple-negative breast cancer is challenging due
to the lack of effective therapeutic options, aggressive behavior and relatively
poor prognosis. Xi Huang pills (XHP) are a well-known traditional Chinese
medicine that demonstrate anticancer activities. The aim of the present study was
to investigate the antitumor effects of XHP on MDA-MB-231 cells in vitro and in
vivo, and its potential underlying molecular mechanisms. In the present study, an
MTT assay was used to evaluate the antiproliferative activity of XHP on MDA-MB
231 cells. In order to investigate the effects further, cell cycle distribution,
apoptosis and mitochondrial membrane potential assays were performed, as well as
western blot analyses. In addition, a tumor xenograft model was employed to
investigate the effects of XHP in vivo. The results of the MTT assay demonstrated
that the viability of MDA-MB-231 cells was markedly inhibited by XHP in a dose-
and time-dependent manner. The inhibitory effect of XHP on the viability of MDA
MB-231 cells was greater when compared with MCF-10A cells. An increase in
apoptosis and loss of mitochondrial membrane potential was observed following 4,
8 and 12 mg/ml XHP treatment of MDA-MB-231 cells. The protein expression levels
of cleaved caspase-3 were increased by 1.62-, 2.13- and 2.19-fold, respectively,
when compared with the untreated controls, whereas no effects on the expression
of B-cell lymphoma 2 (Bcl-2) or Bcl-2-associated X protein (Bax) were observed.
The results of the cell cycle distribution assay analysis demonstrated that XHP
treatment arrested cells at the G2/M phase. In addition, XHP treatment decreased
the expression of cyclin A and increased the expression of p21Cip1. In vivo
experiments revealed that XHP inhibited the growth of MDA-MB-231 xenograft tumors
without body weight loss, and demonstrated similar effects on the protein
expression levels of cleaved caspase 3, cyclin A and p21Cip1 as observed in
vitro. In conclusion, the viability of MDA-MB-231 cells was inhibited by XHP in a
dose-dependent, time-dependent and cell-selective manner in vitro, and the
potential underlying mechanisms may involve apoptosis and cell cycle arrest at
the G2/M phase. XHP may induce apoptosis in MDA-MB-231 cells via the intrinsic
pathway, which does not involve the Bcl-2/Bax ratio. G2/M phase arrest may have
been due to the integrated action of decreased cyclin A expression and increased
p21Cip1 expression. In addition, XHP inhibited the growth of xenograft tumors in
the absence of body weight loss in vivo.
PMID- 29956785
TI - BM-MSCs protect against liver ischemia/reperfusion injury via HO-1 mediated
autophagy.
AB - Ischemia/reperfusion (I/R) injury is considered to be a contributing factor in
liver injury following major hepatic resection or liver transplantation. Bone
marrow mesenchymal stem cells (BM-MSCs) have the potential to protect against
liver I/R injury; however, the precise mechanisms have not been completely
elucidated. Autophagy serves an important role in protecting against various
injuries, including I/R injury. The present study aimed to determine the role of
autophagy and its potential regulatory mechanism in BM-MSC-mediated protection
against liver I/R injury in rats. The results demonstrated that BM-MSCs mitigated
I/R injury and enhanced autophagy in vivo. In addition, inhibition of autophagy
by 3-methyladenine reversed the positive effects of BM-MSCs. Furthermore, heme
oxygenase-1 (HO-1) expression was promoted by BM-MSCs. Using zinc protoporphyrin
IX to inhibit HO-1 demonstrated that HO-1 was important for the promotion of
autophagy. In conclusion, the present study revealed that BM-MSCs protected
against liver I/R injury via the promotion of HO-1-mediated autophagy.
PMID- 29956786
TI - A novel three-miRNA signature predicts survival in cholangiocarcinoma based on
RNA-Seq data.
AB - Accumulating evidence illustrates that many microRNAs (miRNAs) are abnormally
expressed in cholangiocarcinoma and play important roles in tumorigenesis, tumor
progression and metastasis. These miRNAs may serve as prognostic biomarkers and
potential therapeutic targets. The aim of the present study was to identify the
differentially expressed miRNAs in cholangiocarcinoma tissues vs. normal tissues
by analyzing high-throughput data derived from The Cancer Genome Atlas (TCGA)
database. Furthermore, we evaluated the prognostic performance of the
differentially expressed miRNAs and developed a novel three-miRNA signature which
predicted survival in cholangiocarcinoma patients. According to the cut-off
criteria of P<0.01 and |log2FC|>1.0, a total of 100 miRNAs (54 upregulated and 46
downregulated) were found to be differentially expressed and some of them were
significantly associated with clinical features. Of the above 100 miRNAs, we
obtained three miRNAs (miR-10b, miR-22 and miR-551b) which were markedly related
to patient overall survival (OS). Subsequently, a novel three-miRNA signature was
established and validated to be effective to predict survival. The results
demonstrated that the survival rate, as well as the survival time of patients
were obviously enhanced in relation to a lower miRNA signature index. Univariate
and multivariate Cox regression analyses revealed that the three-miRNA signature
was an independent prognostic factor in cholangiocarcinoma. The reliability of
the three-miRNA signature was validated by an independent cohort from Gene
Expression Omnibus (GEO). Furthermore, the functional enrichment analysis
emphasized that the target genes of the aforementioned miRNAs may be involved in
a variety of pathways and processes associated with cancer. Finally, these three
miRNAs were detected for verification of expression using RT-qPCR, and miR-551b
was selected for the verification of biological functions in cholangiocarcinoma
cells. The results revealed that overexpression of miR-551b decreased cancer cell
proliferation and promoted apoptosis. Collectively, the results of the present
study indicated that a specific three-miRNA signature could be considered as an
alternative prognostic marker in cholangiocarcinoma.
PMID- 29956787
TI - Hydrogen peroxide inhibits the growth of lung cancer cells via the induction of
cell death and G1-phase arrest.
AB - Hydrogen peroxide (H2O2) is frequently applied to cultured cells to induce
oxidative stress. The present study investigated the molecular and cellular
effects of exogenous H2O2 on Calu-6 and A549 lung cancer cells. Based on MTT
assays, H2O2 inhibited the growth of Calu-6 and A549 cells with IC50 values of
~50 and 100 uM at 24 h, respectively. Cells treated with H2O2 demonstrated a
considerable G1-phase arrest of the cell cycle. H2O2 dose-dependently augmented
the numbers of dead (trypan blue-positive) and Annexin V-FITC-stained cells in
these cells, which was accompanied by the reduction of Bcl-2 and pro-caspase-3
levels, as well as the upregulation of caspase-3 and -8 activities. In addition,
H2O2 triggered the failure of mitochondrial membrane potential (MMP; DeltaPsim).
However, relatively higher doses of H2O2 did not raise the percentages of sub-G1
cells in these cell lines. All the tested caspase inhibitors (Z-VAD for pan
caspases, Z-DEVD for caspase-3, Z-IETD for caspase-8 and Z-LEHD for caspase-9)
decreased the percentages of sub-G1 and Annexin V-FITC-stained cells in the H2O2
treated Calu-6 and A549 cells. However, caspase inhibitors did not significantly
prevent the loss of MMP (DeltaPsim) in H2O2-treated lung cancer cells. In
conclusion, H2O2 inhibited the growth of Calu-6 and A549 lung cancer cells
through cell death and G1-phase arrest. H2O2-induced cell death resulted from
necrosis, as well as caspase-dependent apoptosis.
PMID- 29956788
TI - Comparison of target volume and clinical effects of four radiotherapy plans for
acute lymphoblastic leukemia prior to hematopoietic stem cell transplantation.
AB - The present study aimed to investigate the variations in target volume, clinical
reaction and transplantation effects of helical tomotherapy (HT)-total body
irradiation (TBI), HT-total marrow and lymphatic irradiation (TMLI), intensity
modulated radiotherapy (IMRT)-TBI and IMRT-TMLI within patients with acute
lymphoblastic leukemia (ALL). A total of 18 patients with ALL were treated with
the four aforementioned radiotherapy plans prior to hematopoietic stem cell
transplantation. A planned prescribed dose of 12 Gy/6 Frequency was administered
to determine planning target volume (PTV). Dosimetry evaluation indexes in PTV
and organs at risk were analyzed. Comparison of clinical untoward effects and the
results of transplantation among the four plans were performed. The conformity
index of HT plans was significantly increased compared with those in IMRT plans.
The mean dose (D) to the lung and volume ratio of target volume occupied by 5 Gy
(V5) in TMLI plans were lower compared with TBI plans. Doses to organs were
controlled within the normal range. Dmax, Dmean and V5 of bilateral lungs and
Dmax and Dmean of bilateral crystalline lens in IMRT plans were significantly
higher compared with HT plans. There were no significant differences in untoward
effects among the four plans. Subsequent to symptomatic treatments with
antiemetic, antidiarrheal and fluid infusion, untoward effects improved, and all
patients demonstrated tolerance to these therapies. A total of six patients
treated with HT-TBI revealed complete and successful transplantation; however,
one patient following transplantation suffered from severe rejection and had
succumbed to mortality due to severe infection. Patients treated with HT-TMLI,
IMRT-TBI and IMRT-TMLI completed successful transplantation and no rejection
responses were observed. Conformity of HT plans are higher than that of IMRT
plans. The four radiotherapy plans exhibit similar clinical untoward effects and
the same transplantation success rate. HT-TMLI is more feasible in dosimetry
compared with HT-TBI, IMRT-TBI and IMRT-TMLI, which require further long-term
observation.
PMID- 29956789
TI - TIMP-3 suppresses the proliferation and migration of SMCs from the aortic neck of
atherosclerotic AAA in rabbits, via decreased MMP-2 and MMP-9 activity, and
reduced TNF-alpha expression.
AB - The present study investigated the role of tissue inhibitor of matrix
metalloproteinase-3 (TIMP-3) in regulating the proliferation, migration,
apoptosis and activity of matrix metalloproteinase (MMP)-2 and -9, during the
development of an atherosclerotic abdominal artery aneurysm (AAA). Experiments
were conducted using rabbit AAA neck (NA) smooth muscle cells (SMCs), to
investigate the potential for TIMP-3 to be used as a novel stent coating in
preventing aortic dilation adjacent to the AAA. The atherosclerotic AAA model was
induced in New Zealand white rabbits via a 6-week high-cholesterol diet, followed
by incubation of the targeted aortic region with elastase. SMCs were isolated
from the aorta adjacent to the aneurysm 30 days after AAA model induction, and
stimulated with 3, 10, 30 or 100 ng/ml TIMP-3. Cell proliferation was
investigated using Cell Counting Kit-8 reagent, migration was examined using a
Boyden chamber assay and apoptotic rate was analyzed using the Annexin V
fluorescein isothiocyanate Apoptosis Detection kit. Gelatin zymography and ELISA
were used to measure the activity of MMP-2 and MMP-9, and the expression of tumor
necrosis factor-alpha (TNF-alpha), respectively. Analysis of cell proliferation
indicated that 10, 30 and 100 ng/ml TIMP-3 reduced cell viability. Cell migration
was decreased by 10, 30 and 100 ng/ml TIMP-3. MMP-2 activity was inhibited by 10,
30 and 100 ng/ml TIMP-3, and MMP-9 activity was suppressed by 30 and 100 ng/ml
TIMP-3. The protein levels of secreted TNF-alpha were reduced by 10, 30 and 100
ng/ml TIMP-3. The present study demonstrated the ability of 30 and 100 ng/ml TIMP
3 to attenuate migration and proliferation, and to inhibit the activity of MMP-2,
MMP-9 and TNF-alpha secretion of NA SMCs. In conclusion, TIMP-3 may be considered
a potential therapeutic drug for use in a novel drug-eluting stent, to attenuate
the progressive dilation of the aortic NA.
PMID- 29956791
TI - The close association between IL-12Rbeta2 and p38MAPK, and higher expression in
the early stages of NSCLC, indicates a good prognosis for survival.
AB - Interleukin-12 receptor (IL-12R) and p38 mitogen-activated protein kinase
(p38MAPK) serve an important role in non-small cell lung cancer (NSCLC). It has
previously been suggested that IL-12Rbeta2 may be involved in key regulatory
pathways and interacts with the p38MAPK signaling pathway. The present study
aimed to elucidate the possible association and roles of IL-12Rbeta2 and p38MAPK
in NSCLC. The protein expression levels of IL-12Rbeta2 and p38MAPK were measured
in 230 NSCLC tissue samples by immunohistochemistry (IHC) and western blot
analyses. In addition, an immunofluorescence assay was used to observe the
expression levels of these proteins in A549 and H358 cells. The associations
between IL-12Rbeta2, p38MAPK and clinical characteristics, were evaluated by
Pearson chi2 and Spearman correlation tests. Kaplan-Meier plots (log-rank test)
and Cox proportional hazard models were used to analyze overall survival (OS).
Compared with in benign pulmonary tissues, the expression levels of IL-12Rbeta2
and p38MAPK were not demonstrated to be significantly different in I+II
pathological tumor-node-metastasis (pTNM) stage NSCLC tissues; however, reduced
expression was detected in III+IV pTNM stage NSCLC tissues. Analysis of the
association between advanced stage pTNM and the expression of both proteins
demonstrated a significantly decreased Allred score (both P<0.0001), which was
confirmed by IHC and western blot analyses. The IHC results demonstrated a
significant correlation between IL-12Rbeta2 and p38MAPK expression (r=0.415,
P=0.0143). By analyzing IL-12Rbeta2, p38MAPK expression and clinical
characteristics, it was identified that IL-12Rbeta2 was significantly associated
with gender (P=0.0168), age (P=0.0341), histological type (P<0.0001) and pTNM
stage (P<0.0001). p38MAPK demonstrated a strong association with gender
(P=0.0082) and pTNM stage (P<0.0001). The results of a Kaplan-Meier analysis
indicated that positive IL-12Rbeta2 and p38MAPK expression was associated with
increased OS compared with negative protein expression. The Cox proportional
hazard models revealed that IL-12Rbeta2 and p38MAPK predicted a long OS. To the
best of our knowledge, the present study is the first to reveal a close
association between IL-12Rbeta2 and p38MAPK, and their possible function in NSCLC
progression. It further demonstrated that expression of both proteins was lower
with advanced pTNM staging, whereas a high expression of both proteins was
associated with improved prognosis in NSCLC.
PMID- 29956790
TI - Effects of isomaltulose on insulin resistance and metabolites in patients with
non-alcoholic fatty liver disease: A metabolomic analysis.
AB - Insulin resistance is associated with a poor prognosis in non-alcoholic fatty
liver disease (NAFLD) patients. Isomaltulose, a naturally-occurring disaccharide,
is reported to improve glucose and lipid metabolisms in obese patients. The
present study aimed to investigate the effects of isomaltulose on insulin
resistance and various metabolites in NAFLD patients. Five male patients with
NAFLD consumed 20 g isomaltulose or sucrose (control). Changes in insulin
resistance and metabolites were evaluated by alterations of serum C-peptide
immunoreactivity (CPR) and metabolomic analysis from baseline to 15 min after the
administration, respectively. There was no significant difference in changes of
blood glucose level; however, the CPR level was significantly decreased in the
Isomaltulose group compared to the control group (0.94+/-0.89 vs. -0.12+/-0.31,
P=0.0216). In a metabolomic analysis, a significant alteration was seen in 52
metabolites between the control and Isomaltulose groups. In particular, the
taurodeoxycholic acid level significantly increased approximately 12.5-fold, and
the arachidonic acid level significantly decreased approximately 0.01-fold.
Together, it present study demonstrated that isomaltulose improved insulin
resistance in NAFLD patients. It was also revealed that isomaltulose affects
taurodeoxycholic acid and arachidonic acid. Thus, isomaltulose may have a
beneficial effect on insulin resistance through alterations of bile acid and
fatty acid metabolisms in NAFLD patients.
PMID- 29956793
TI - Thymoquinone inhibits metastatic phenotype and epithelial-mesenchymal transition
in renal cell carcinoma by regulating the LKB1/AMPK signaling pathway.
AB - Thymoquinone, isolated from the seeds of Nigella sativa, has exhibited antitumor
properties in a variety of cancer types. However, few studies have investigated
the effect of thymoquinone (TQ) on migration and invasion in renal cell carcinoma
(RCC). In the present study, our results confirmed that TQ significantly
inhibited the migration and invasion of the human RCC 769-P and 786-O cell lines,
as demonstrated by wound healing and Transwell assays. Additionally, TQ
upregulated the expression of E-cadherin and downregulated the expression of
Snail, ZEB1 and vimentin at the mRNA and protein levels in a concentration
dependent manner. Subsequently, the phosphorylation levels of liver kinase B1
(LKB1) and AMP-activated protein kinase (AMPK) were increased upon TQ treatment.
To further validate the role of LKB1/AMPK signaling, we revealed that TQ-mediated
increase of E-cadherin level and reduction of Snail level could be further
enhanced by LKB1 overexpression. Furthermore, co-treatment with the AMPK
inhibitor Compound C attenuated the anti-metastatic effect of TQ on RCC and
partially abrogated the high expression of E-cadherin and the low expression of
Snail mediated by TQ. In contrast, the AMPK activator AICAR demonstrated the
opposite effect. Collectively, the present study revealed that TQ could markedly
suppress the metastatic phenotype and reverse the epithelial-mesenchymal
transition in RCC by regulating the LKB1/AMPK signaling pathway, indicating that
TQ may be a potential therapeutic candidate against RCC.
PMID- 29956792
TI - DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric
cancer.
AB - Dual-specificity phosphatase-1 (DUSP1) is an oncogene that is associated with
cancer progression following drug resistance. In order to investigate the
potential relationship between DUSP1 and apatinib resistance in gastric cancer
cells, we preformed many assays to study this problem. DUSP1 gene was detected by
RT-qPCR assay, proteins in MAPK pathway were quantified by western blot assay,
and CCK-8 assay, flow cytometry and Hoechest 33342 stain were performed to detect
the resistance of cells, cell cycles and apoptosis, respectively.
Immunohistochemical staining was used to discover the expression of DUSP1 protein
in patients' tumor or paratumor tissues. It was found that apatinib (Apa)
resistant gastric cancer (GC) cells showed increased expression of DUSP1, whereas
the knockdown of DUSP1 in resistant cells resensitized these cells to Apa. The
restored sensitivity to Apa was the result of inactivation of mitogen-activated
protein kinase (MAPK) signaling and the induction of apoptosis. The in vitro use
of Apa in combination with a DUSP1 inhibitor, triptolide, exerted significant
effects on inhibiting the expression of DUSP1, growth inhibition, and apoptosis
via the inactivation of MAPK signaling. In patients who did not undergo
chemotherapy or targeted therapy, the expression of DUSP1 in adjacent tissues was
higher when compared with that observed in tumor tissues. In addition, the
expression of DUSP1 was higher in the early stages of GC than in the advanced
stages. The expression of DUSP1 in tumor tissues was not associated with the
survival rate of the patients. Therefore, increased expression of DUSP1 may be
responsible for Apa resistance, and DUSP1 may serve as a biomarker for Apa
efficacy. In conclusion, inducing the downregulation of DUSP1 may be a promising
strategy to overcome Apa resistance.
PMID- 29956794
TI - Discovery of rafoxanide as a dual CDK4/6 inhibitor for the treatment of skin
cancer.
AB - Since cyclin-dependent kinases 4/6 (CDK4/6) play pivotal roles in cell cycle
regulation and are overexpressed in human skin cancers, CDK4/6 inhibitors are
potentially effective drugs for skin cancer. In the present study, we present a
mixed computational and experimental study attempting to repurpose approved small
molecule drugs as dual CDK4/6 inhibitors for skin cancer treatment. We performed
structure-based virtual screening using the docking software idock, targeting an
ensemble of CDK4/6 structures. We identified and selected nine compounds with
significant predicted scores, and evaluated their cytotoxic effects in vitro in
A375 and A431 human skin cancer cell lines. Rafoxanide was found to exhibit the
highest cytotoxic effects (IC50: 1.09 uM for A375 and 1.31 uM for A431 cells).
Consistent with the expected properties of CDK4/6 inhibitors, rafoxanide
significantly increased the G1 phase population. Notably, we revealed that
rafoxanide specifically decreased the expression of CDK4/6, cyclin D,
retinoblastoma protein (Rb) and the phosphorylation of CDK4/6 and Rb.
Furthermore, the anticancer effect of rafoxanide was demonstrated in vivo in
BALB/C nude mice subcutaneously xenografted with human skin cancer A375 cells.
Rafoxanide (40 mg/kg, i.p.) exhibited significant antitumor activity, comparable
to that of oxaliplatin (5 mg/kg, i.p.). The combined administration of rafoxanide
and oxaliplatin produced a synergistic therapeutic effect. To the best of our
knowledge, the present study is the first to indicate that rafoxanide inhibits
CDK4/6 activity and is a potential candidate drug for the treatment of human skin
cancer.
PMID- 29956795
TI - Genome-wide profiling of lncRNA expression patterns in patients with acute
promyelocytic leukemia with differentiation therapy.
AB - Long non-coding RNAs (lncRNAs) are crucial factors in acute promyelocytic
leukemia (APL) cell differentiation. However, their expression patterns and
regulatory functions during all-trans-retinoic acid (ATRA)-induced APL
differentiation remain to be fully elucidated. The profile of dysregulated
lncRNAs between three bone marrow (BM) samples from patients with APL post
induction and three BM samples from untreated matched controls was examined with
the Human Transcriptome Array 2.0. The dysregulated lncRNA expression of an
additional 27 APL BM samples was validated by reverse transcription-quantitative
polymerase chain reaction (RT-qPCR) analysis. The lncRNA functions were predicted
through co-expressed messenger RNA (mRNA) annotations. Co-expressed lncRNA-mRNA
networks were constructed to analyze the functional pathways. In total, 825
lncRNAs and 1,218 mRNAs were dysregulated in the treated APL BM group, compared
with the untreated APL BM group. The expression of 10 selected lncRNAs was
verified by RT-qPCR analysis. During APL differentiation, NONHSAT076891 was the
most upregulated lncRNA, whereas TCONS_00022632-XLOC_010933 was the most
downregulated. Functional analysis revealed that several lncRNAs may exert
activities in biological pathways associated with ATRA-induced APL
differentiation through cis and/or trans regulation of mRNAs. The findings of the
present study assist in explaining the contributions of lncRNAs in APL myeloid
differentiation and improve current knowledge on the potential mechanisms
regarding dysregulated lncRNA expression in ATRA-induced APL differentiation.
PMID- 29956796
TI - Label-free quantitative proteomics and bioinformatics analyses of alcoholic liver
disease in a chronic and binge mouse model.
AB - As a significant cause of mortality and morbidity, alcoholic liver disease (ALD)
has been widely investigated. However, little is known about the underlying
metabolic mechanisms involved in the complicated pathological processes of ALD.
The present study used label-free quantitative proteomics and bioinformatics
analyses to investigate the differentially expressed proteins (DEPs) and their
functions in the livers of alcohol-feed (AF) and control pair-feed (PF) mice. As
a result, 87 upregulated DEPs and 133 downregulated DEPs were identified in AF
liver tissues compared with PF livers. Gene ontology and Kyoto encyclopedia of
genes and genomes bioinformatics analyses demonstrated that the DEPs were
significantly enriched in 'protein binding', 'metabolism', 'signal conduction'
and 'immune response'. The expression of several core proteins including thyroid
hormone receptor interactor 12 (TRIP12), NADH dehydrogenase (ubiquinone)1 alpha
subcomplex, assembly factor 3 (NDUFAF3) and guanine monophosphate synthetase
(GMPS) was validated by reverse transcription-quantitative polymerase chain
reaction (RT-qPCR) in a larger series of samples. The RT-qPCR results confirmed
that TRIP12, NDUFAF3 and GMPS genes were significantly differentially expressed
in between the AF and PF samples. These results extend our understanding of the
molecular mechanisms underlying the occurrence and development of ALD. The
present study indicated that the majority of DEPs serve vital roles in multiple
metabolic pathways and this extends our knowledge of the molecular mechanisms
involved in the occurrence and progression of ALD.
PMID- 29956797
TI - Ursolic acid elicits intrinsic apoptotic machinery by downregulating the
phosphorylation of AKT/BAD signaling in human cisplatin-resistant oral cancer CAR
cells.
AB - Oral squamous cell carcinoma (OSCC) is a type of cancer with high morbidity and
mortality rates worldwide; it also demonstrates chemotherapeutic resistance.
Triterpenoid ursolic acid has been shown to exhibit various biological activities
and anticancer effects in several preclinical studies. In our previous study,
human cisplatin-resistant oral cancer CAR cells were established, and the present
study aimed to further examine the effects of ursolic acid on CAR cells. The
results revealed that ursolic acid inhibited CAR cell viability, as determined
using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
Ursolic acid-induced cell death was mediated through a caspase-dependent pathway,
determined with the pan-caspase inhibitor, z-VAD-fmk. Ursolic acid also increased
the activities of caspase-3 and caspase-9 in CAR cells, determined by a
colorimetric assay. Specifically, the production of reactive oxygen species and
loss of mitochondrial membrane potential, detected by flow cytometry, were
observed in the ursolic acid-treated CAR cells. The apoptosis-associated
signaling showed that ursolic acid decreased the phosphorylation of AKT (Ser473)
and B-cell lymphoma 2 (Bcl-2)-associated agonist of cell death (BAD; Ser136), and
the protein levels of Bcl-2 and Bcl-extra large (Bcl-xL), and increased the
expression of BAD and Bcl-2-associated X (Bax) protein in CAR cells. In summary,
the results supported the potential application of ursolic acid against drug
resistant oral carcinoma and to improve oral anticancer efficacy in the near
future.
PMID- 29956798
TI - Intraperitoneal oxaliplatin administration inhibits the tumor immunosuppressive
microenvironment in an abdominal implantation model of colon cancer.
AB - Recent studies have demonstrated that some chemotherapeutic drugs can enhance
antitumor immunity by eliminating and inactivating immunosuppressive cells.
Oxaliplatin (OXP) induces immunogenic cell death by increasing the immunogenicity
of cancer cells. However, the effects of OXP on the tumor immunosuppressive
microenvironment remain unclear. The aim of the present study was to evaluate the
antitumor activity of OXP by intraperitoneal (i.p.) administration in an
abdominal implantation model of colon cancer and tested the tumor immune
microenvironment to observe whether OXP affects the local immune inhibitory cell
populations. Abdominal metastasis models were established by inoculation of CT26
cells. The antitumor efficacy of OXP and the tumor immune microenvironment were
evaluated. The tumors and spleens of mice were harvested for flow cytometric
analysis. Cluster of differentiation (CD)-8+CD69+ T cells, regulatory T cells
(Tregs), CD11b+F4/80high macrophages and myeloid-derived suppressor cells (MDSCs)
were evaluated by flow cytometric analysis. In vivo i.p. administration of OXP
inhibited tumor growth in the abdominal metastasis model. Furthermore, OXP was
observed to increase tumor-infiltrating activated CD8+ T cells in tumors,
decrease CD11b+F4/80high macrophages in tumors and decrease MDSCs in the spleen.
These results suggested that i.p. administration of OXP alone may inhibit tumor
cell growth and induce the antitumor immunostimulatory microenvironment by
eliminating immunosuppressive cells.
PMID- 29956799
TI - Effects of constrained dynamic loading, CKIP-1 gene knockout and combination
stimulations on bone loss caused by mechanical unloading.
AB - Mechanical stimulation plays an important role in maintaining the growth and
normal function of the skeletal system. Mechanical unloading occurs, for example,
in astronauts spending long periods of time in space or in patients on prolonged
bed rest, and causes a rapid loss of bone mass. Casein kinase 2-interacting
protein-1 (CKIP-1) is a novel negative bone regulation factor that has been
demonstrated to reduce bone loss and enhance bone formation. The aim of this
study was to investigate the effect of constrained dynamic loading (Loading) in
combination with CKIP-1 gene knockout (KO) on unloading-induced bone loss in tail
suspension mice. The blood serum metabolism index [alkaline phosphatase (ALP)
activity and osteocalcin (OCN) levels], tibia mechanical behavior (including bone
trabecular microstructure parameters and tibia biomechanical properties),
osteoblast-related gene expression [ALP, OCN, collagen I and bone morphogenetic
protein-2 and osteoprotegerin (OPG)] and osteoclast-related gene expression
[receptor activators of NF-kB ligand (RANKL)] were measured. The results
demonstrated that mice experienced a loss of bone mass after four weeks of tail
suspension compared with a wild type group. The mechanical properties,
microarchitecture and mRNA expression were significantly increased in mice after
Loading + KO treatment (P<0.05). Furthermore, compared with loading or KO alone,
the ratio of OPG/RANKL was increased in the combined treatment group. The
combined effect of Loading + KO was greater than that observed with loading or KO
alone (P<0.05). The present study demonstrates that Loading + KO can counter
unloading-induced bone loss, and combining the two treatments has an additive
effect. These results indicate that combined therapy could be a novel strategy
for the clinical treatment of disuse osteoporosis associated with space travel or
bed rest.
PMID- 29956800
TI - Interaction with adipocytes induces lung adenocarcinoma A549 cell migration and
tumor growth.
AB - Adipocytes have been demonstrated to promote the progression of various tumors
through modulation of cancer cell metabolism. However, their role in lung cancer
progression remains undetermined. In the present study, adipocytes and lung
adenocarcinoma A549 cells were cultured in a Transwell co-culture system. Cancer
cells were additionally cultured in conditioned medium, obtained from adipocytes
or co-cultured cells. A MTT and colony formation assay were performed to assess
A549 cell proliferation. The expression of epithelial-mesenchymal transition
protein markers E-cadherin and vimentin were measured by western blotting. A549
cell migration and invasion was determined with wound healing, Transwell and
Matrigel assays. Oil Red-O staining was used to evaluate intracellular lipid
content. Colorimetric assays were utilized to detect free fatty acid, glucose
uptake, lactate production and triglyceride content in cells. The results
revealed a reciprocal interaction between adipocytes and A549 cells, which
significantly enhanced A549 cell proliferation and metastasis; whereas, the
expression of E-cadherin was decreased and vimentin was increased in A549 cells.
Additionally, A549 cells exhibited metabolic reprogramming in vitro following co
culture with adipocytes. It was demonstrated that lipid droplets accumulation,
glucose consumption and lactate production increased in tumor cells exposed to
adipocytes. Furthermore, adipocytes co-cultured with A549 cells exhibited a
decrease in the number and size of lipid droplets, a decrease in the
intracellular triglyceride content and a significant increase in the release of
free fatty acids. These findings highlighted the crucial role of adipocytes in
the modulation of lung adenocarcinoma A549 cell metabolism and suggested the
involvement of adipocytes in lung cancer progression.
PMID- 29956801
TI - Tanshinone IIA improves hypoxic ischemic encephalopathy through TLR-4-mediated NF
kappaB signal pathway.
AB - Hypoxic ischemic encephalopathy (HIE) is the most common brain injury following
hypoxia and/or ischemia caused by various factors during the perinatal period,
resulting in detrimental neurological deficits in the nervous system. Tanshinone
IIA (Tan-IIA) is a potential agent for the treatment of cardiovascular and
cerebrovascular diseases. In this study, the efficacy of Tan-IIA was investigated
in a newborn mouse model of HIE. The dynamic mechanism of Tan-IIA was also
investigated in the central nervous system of neonate mice. Intravenous injection
of Tan-IIA (5 mg/kg) was administered and changes in oxidative stress,
inflammation and apoptosis-associated proteins in neurons. Histology and
immunohistochemistry was used to determine infarct volume and the number of
damaged neurons by Fluoro-Jade C staining. The effects of Tan-IIA on mice with
HIE were evaluated by body weight, brain water content, neurobehavioral tests and
blood-brain barrier permeability. The results demonstrated that the apoptosis
rate was decreased following Tan-IIA administration. Expression levels of pro
apoptotic proteins, caspase-3 and caspase-9 and P53 were downregulated.
Expression of Bcl-2 anti-apoptotic proteins was upregulated by Tan-IIA treatment
in neuro. Results also found that Tan-IIA treatment decreased production of
inflammatory cytokines such as interleukin-1, tumor necrosis factor-alpha, C-X-C
motif chemokine 10, and chemokine (C-C motif) ligand 12. Oxidative stress was
also reduced by Tan-IIA in neurons, as determined by the expression levels of
superoxide dismutase, glutathione and catalase, and the production of reactive
oxygen species. The results demonstrated that Tan-IIA treatment reduced the
infarct volume and the number of damaged neurons. Furthermore, body weight, brain
water content and blood-brain barrier permeability were markedly improved by Tan
IIA treatment of newborn mice following HIE. Furthermore, the results indicated
that Tan-IIA decreased Toll-like receptor-4 (TLR-4) and nuclear factor-kappaB (NF
kappaB) expression in neurons. TLR-4 treatment of neuronal cell in vitro addition
stimulated NF-kappaB activity, and further enhanced the production of
inflammatory cytokines and oxidative stress levels in neurons. In conclusion,
these results suggest that Tan-IIA treatment is beneficial for improvement of HIE
through TLR-4-mediated NF-kappaB signaling.
PMID- 29956803
TI - Ophiopogonin B suppresses the metastasis and angiogenesis of A549 cells in vitro
and in vivo by inhibiting the EphA2/Akt signaling pathway.
AB - Lung adenocarcinoma is the most common metastatic cancer, and is associated with
high patient mortality. Therefore, investigation of anti-metastatic treatments
for lung adenocarcinoma is crucial. Ophiopogonin B (OP-B) is a bioactive
component of Radix Ophiopogon Japonicus, which is often used in Chinese
traditional medicine to treat pulmonary disease. Screening of transcriptome and
digital gene expression (DGE) profiling data in NSCLC cell lines showed that OP-B
regulated the epithelial-mesenchymal transition (EMT) pathway in A549 cells.
Further results showed that 10 umol/l OP-B downregulated EphA2 expression and
phosphorylation (Ser897) in A549 cells but upregulated them in NCI-H460 cells.
Meanwhile, the Ras/ERK pathway was unaffected in A549 cells and stimulated in NCI
H460 cells. More importantly, detection of the EMT pathway showed that OP-B
treatment increased the epithelial markers ZO-1 and E-cadherin and decreased the
expression of the mesenchymal marker N-cadherin and the transcriptional
repressors Snail, Slug and ZEB1. Furthermore, through Transwell migration and
scratch wound healing assays, we found that 10 umol/l OP-B significantly reduced
the invasion and migration of A549 cells. In vivo, we found that 75 mg/kg OP-B
inhibited A549 cell metastasis in a pulmonary metastasis nude mouse model. In
addition, we also found that 10 umol/l OP-B significantly inhibited tube
formation in EA.hy926 cells. The expression of VEGFR2 and Tie-2, the
phosphorylation of Akt (S473) and PLC (S1248), and the levels of EphA2 and
phosphorylated EphA2 (S897) were all inhibited by OP-B in this cell line. In
vivo, using a Matrigel plug assay, we found that OP-B inhibited angiogenesis and
the hemoglobin content of A549 transplanted tumors. Taken together, OP-B
inhibited the metastasis and angiogenesis of A549 cells by inhibiting EphA2/Akt
and the corresponding pathway. The investigation gives new recognition to the
anticancer mechanism of OP-B in NSCLC and this compound is a promising inhibitor
of metastasis and angiogenesis of lung adenocarcinoma cells.
PMID- 29956802
TI - Inhibition of autophagy enhanced cobalt chloride-induced apoptosis in rat
alveolar type II epithelial cells.
AB - Hypoxia is a type of cellular stress that may result in apoptosis and autophagy.
The molecular mechanisms underlying the association between autophagy and
apoptosis remain unclear, particularly in hypoxic conditions. Transmission
electron microscope, AO-PI staining, flow cytometry and western blot were used to
examine the crosstalk between autophagy and apoptosis in hypoxic conditions. Rat
alveolar type II epithelial RLE-6TN cells were cultured in a long-term hypoxic
environment established by cobalt (II) chloride. It was demonstrated that
autophagy and apoptosis occurred in RLE-6TN cells under hypoxic conditions.
Treatment of RLE-6TN cells with the autophagy inhibitor 3-methyladenine increased
the generation of reactive oxygen species, mitochondrial damage and hypoxia
induced apoptosis. The expression of caspases, particularly caspase-9, increased
and may have participated in these processes. The data indicated that the
inhibition of autophagy enhanced apoptosis through the mitochondria-mediated
intrinsic pathway. These findings provide important insight into the molecular
mechanism of autophagy and apoptosis crosstalk. This may provide new insights
into pulmonary disease surveillance, diagnosis and treatment.
PMID- 29956804
TI - Metformin suppresses the invasive ability of pancreatic cancer cells by blocking
autocrine TGF-beta1 signaling.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive neoplasm with a 5
year survival rate of <8%. Metformin, the most widely used antidiabetic drug in
the world, has been shown to exert anticancer activities in epidemiological and
animal studies. Our previous studies revealed that metformin suppressed
desmoplasia in PDAC by reducing TGF-beta1 production in cancer cells. The aim of
the present study was to investigate the effects of metformin on invasion and
epithelial-mesenchymal transition (EMT) in pancreatic cancer and to reveal the
underlying mechanisms. In the present study, we revealed that metformin
suppressed migration, invasion and EMT changes in pancreatic cancer cells.
Furthermore, metformin reduced TGF-beta1 production and Smad2/3 phosphorylation
in pancreatic cancer cells. In addition, treatment with recombinant TGF-beta1
recovered the metformin-mediated invasion inhibition and EMT changes. Treatment
with metformin also suppressed tumor growth, invasion and EMT in LSL-KrasG12D/+,
Trp53fl/+and Pdx1-Cre (KPC) transgenic mice that harbor spontaneous pancreatic
cancer. Collectively, our study revealed a new possible mechanism for the
antitumor effects of metformin via autocrine TGF-beta1/Smad2/3 signaling in PDAC.
PMID- 29956805
TI - Tumor-penetrating peptide fused EGFR single-domain antibody enhances radiation
responses following EGFR inhibition in gastric cancer.
AB - Radiotherapy has been the primary method for the local control of several types
of unresectable tumor, including gastric cancer. Patients with gastric cancer
frequently express high levels of epidermal growth factor receptor (EGFR), which
have been found to increase following radiotherapy treatment. This provides a
basis for the combination of antibodies targeting EGFR and radiotherapy. In our
previous study, a protein (anti-EGFR-iRGD) with bispecific targets and high
permeability was constructed, and its effects on inhibiting the proliferation of
gastric cancer cells was investigated. In the present study, the capacity of anti
EGFR-iRGD to modulate a radiation response was investigated and the specific
mechanisms underlying these interactions were evaluated in gastric cancer cell
lines and xenografts exhibiting high levels of EGFR. The radioenhancement of anti
EGFR-iRGD was associated with inhibited radiation-induced upregulation of EGFR,
inhibited cell proliferation and promotion of cell apoptosis. In addition, anti
EGFR-iRGD appeared to permeate more into the tumor tissue following radiation.
These findings indicated that the recombinant protein anti-EGFR-iRGD was a
selective and effective radiosensitizer in EGFR-overexpressing gastric cancer
cells and xenografts. These results further suggested that anti-EGFR-iRGD is a
potential superior EGFR-targeted therapy combined with radiotherapy. Overall, the
present study suggested that anti-EGFR-iRGD may be a promising candidate for
preclinical and clinical use.
PMID- 29956806
TI - Decreased expression of TROAP suppresses cellular proliferation, migration and
invasion in gastric cancer.
AB - Trophinin associated protein (TROAP) is a cytoplasmic protein required for
spindle assembly and cell invasion; however, its biological function in cancer
remains to be elucidated. In the present study, by analyzing three independent
datasets from the Oncomine database, it was identified that TROAP mRNA expression
was upregulated in gastric cancer (GC) tissues compared with normal counterparts.
Furthermore, elevated expression of TROAP was associated with poor survival in
patients with GC, as predicted using Kaplan-Meier analysis. TROAP was knocked
down to verify its functional role in gastric cancer cell lines, SGC-7901 and
MGC80-3. MTT assay was used to analyze cell proliferation. Cell cycle
progression, and migration and invasion were determined using flow cytometry and
Transwell assay, respectively. In vitro experiments demonstrated that knockdown
of TROAP significantly suppressed cell proliferation, G1 to S cell cycle
transition, and the migration and invasion ability of GC cells. The results of
the present study suggest that TROAP is overexpressed in GC and serves an
oncogenic role in gastric cancer by affecting cell proliferation and invasion.
PMID- 29956807
TI - S100B promotes chemoresistance in ovarian cancer stem cells by regulating p53.
AB - Chemoresistance is one of the most important causes of ovarian cancer-related
deaths. Recently, cancer stem cells (CSCs) have been recognized as the source of
chemoresistance in ovarian cancer. However, the underlying mechanisms that
regulate the chemoresistance of ovarian CSCs (OCSCs) remain unclear. The aim of
the present study was to investigate the roles of S100B in the regulation of OCSC
chemoresistance, which provides a novel therapeutic target. We observed high
expression of S100B in CD133+ OCSCs derived from ovarian cancer cell lines and
primary tumors and in cisplatin-resistant patient samples. Then, we determined
that S100B knockdown promoted the apoptosis of OCSCs after treatment with
different concentrations of cisplatin. The underlying mechanism of S100B-mediated
chemoresistance in OCSCs may be through p53 inhibition. Furthermore, drug
resistance genes, including MDR1 and MRP1, were involved in the process of S100B
mediated OCSC chemoresistance. In conclusion, our results elucidated the
importance of S100B in the maintenance of OCSC chemoresistance, which may provide
a promising therapeutic target for ovarian cancer.
PMID- 29956808
TI - Inhibition of RAD54B suppresses proliferation and promotes apoptosis in hepatoma
cells.
AB - RAD54 homolog B is a central motor protein of homologous recombination (HR),
which plays an important role in the development and evolution of human cancer.
Recent studies have indicated that RAD54B is aberrantly expressed in a variety of
cancers and exhibits numerous biological functions, including participating in
the repair of DNA double strand breaks. However, the expression and function of
RAD54B in liver cancer have not yet been reported. The aim of the present study
was to investigate the expression of RAD54B and elucidate its role in liver
cancer cell lines by inhibiting RAD54B using a lentivirus-mediated shRNA
interference system. We also assessed the effect of RAD54B on cell proliferation,
colony formation, cell cycle distribution and cell apoptosis in BEL-7404 and SMMC
7721 cell lines using shRAD54B or shCtrl transfection. Furthermore, we analyzed
the relationship between the expression of RAD54B protein, as measured by
immunohistochemical staining, and the prognosis of patients with hepatoma. We
found that RAD54B was highly expressed in liver cancer cell lines compared with
the normal hepatic cell line LO2. Similarly, positive expression of RAD54B, which
is associated with poor prognosis, was also observed in 52/83 samples of liver
cancer tissue. Additionally, RAD54B downregulation significantly inhibited cell
proliferation and colony formation, while also inducing G1/S cell cycle arrest
and apoptosis in BEL-7404 and SMMC-7721 cells. These results indicated that
RAD54B has oncogenic properties, and may be a potential treatment target for
liver cancer patients.
PMID- 29956809
TI - Adiponectin inhibits migration and invasion by reversing epithelial-mesenchymal
transition in non-small cell lung carcinoma.
AB - Adiponectin is the most abundant adipokine in the tumor microenvironment. The
role of this protein in tumor progression, however, remains controversial. In the
present study, we aimed to investigate the effects of adiponectin on the
abilities of migration and invasion in non-small cell lung carcinoma (NSCLC).
Using NSCLC cell lines, we examined the effects of adiponectin on cell migration
and invasion using Transwell assays. Expression of epithelial-mesenchymal
transition markers was examined via microscopy and western blotting. We also
performed a knockdown of Twist, AdipoR1 and AdipoR2 in NSCLC cells with siRNAs.
The addition of adiponectin to NSCLC cells inhibited both the migration and
invasion abilities. Furthermore, we found that NSCLC cells displayed increased
epithelial marker expression and downregulation of mesenchymal marker expression
following adiponectin administration. Twist AdipoR1 and AdipoR2 knockdown
reversed the inhibitory effects of adiponectin on migration and invasion in NSCLC
and epithelial-mesenchymal transition. Exogenous adiponectin significantly
impaired the migratory and invasive capacities of NSCLC cells through reversal of
EMT, suggesting that adiponectin may be a novel promising therapeutic approach
against NSCLC.
PMID- 29956810
TI - Impact of sex, body mass index and initial pathologic diagnosis age on the
incidence and prognosis of different types of cancer.
AB - Cancer represents a significant challenge for humankind, as early diagnosis and
treatment are difficult to achieve. To systemically investigate the effect of
sex, body mass index (BMI) and age on cancer incidence and prognosis, the data
from 14,504 cases of cancer were downloaded from The Cancer Genome Atlas (TCGA).
BMI was used to categorize each person as underweight, normal weight, overweight
or obese. Two- and five-year survival rates were applied to estimate the
prognosis for each cancer type. All data were statistically analyzed. We
identified that males were more susceptible to lung, liver and skin cancer when
compared with females, whereas females were more susceptible to thyroid, breast
and adrenal cortex cancer. High BMI (>25) was positively associated with the
occurrence of cancer, although patients with high BMI at the time of initial
diagnosis had higher two/five-year survival rates. The survival rates for cancer
were positively correlated with the age at initial pathologic diagnosis. Some
types of cancer were associated with particularly young ages of onset, including
adrenocortical carcinoma, cervical and endocervical cancers, brain lower grade
glioma, pheochromocytoma and paraganglioma, testicular germ cell tumors and
thyroid carcinoma. Hence, the early diagnosis and prognosis for these cancers
need to be improved. In conclusion, sex, BMI and age are associated with the
incidence and survival rates for cancers. These results could be used to
supplement precision and personalized medicine.
PMID- 29956811
TI - miR-195-5p regulates multi-drug resistance of gastric cancer cells via targeting
ZNF139.
AB - Gastric cancer (GC) is one of the most common malignant tumors with a high
mortality rate. Reversing the multi-drug resistance (MDR) of GC offers the
potential for significant enhancement of the effect of chemotherapy and
improvement of prognosis. Aberrant microRNA expression can attribute to the
pathogenesis of GC. However, the effects of microRNA (miR)-195-5p on the MDR of
GC cells remains to be fully elucidated. In the present study, the effect of miR
195-5p in regulating the MDR of GC cells was investigated. Reverse transcription
quantitative-polymerase chain reaction was used to analyze the levels of miR-195
5p in GC cells. Western blot analysis was performed to analyze the protein levels
of ZNF139, P-gp, BCL-2 and MRP1. The chemosensitivity of GC cells was determined
by MTT. The results showed that the expression of miR-195-5p was decreased in
poorly differentiated GC tissues with a higher chemosensitivity. The
overexpression of miR-195-5p promoted the chemosensitivity of GC cells.
Bioinformatics analysis indicated that Zing finger 139 (ZNF139) was a target of
miR-195-5p. miR-195-5p negatively regulated the expression of ZNF139 by binding
to its 3'-untranslated region. The silencing of ZNF139 promoted the
chemosensitivity of GC cells, and the downregulation of ZNF139 reversed the
effect of miR-195-5p inhibitor on the chemosensitivity of GC cells. In
conclusion, miR-195-5p regulated the MDR of GC cells via targeting ZNF139.
PMID- 29956813
TI - Downregulation of TRIM58 expression is associated with a poor patient outcome and
enhances colorectal cancer cell invasion.
AB - TRIM58 is a member of the tripartite motif protein (TRIM) family of E3 ubiquitin
ligases. Aberrant gene methylation of TRIM58 has been reported in liver and lung
cancer and indicates a poor patient prognosis. However, the expression level and
functional role of TRIM58 in colorectal cancer (CRC) have yet to be elucidated.
In the present study, we found that TRIM58 expression was significantly
suppressed in human CRC and was inversely correlated with CRC progression.
Additionally, overall survival was significantly reduced in patients with low
TRIM58 expression in CRC tumors. In vitro studies demonstrated that ectopic
TRIM58 overexpression strongly inhibited CRC cell invasion but had minimal
effects on cell proliferation, colonization and migration. Furthermore, TRIM58
suppression enhanced the expression of epithelial-to-mesenchymal transition (EMT)
and matrix metalloproteinase (MMP) genes. Thus, our findings suggest that TRIM58
is a potential prognostic marker of CRC and functions as a tumor-suppressor gene
via inhibition of cancer cell invasion through EMT and MMP activation.
PMID- 29956812
TI - Parathyroid hormone 1-34 inhibits senescence in rat nucleus pulposus cells by
activating autophagy via the m-TOR pathway.
AB - Osteoporosis is closely associated with intervertebral disc degeneration. While
parathyroid hormone (PTH) 1-34, which is an established drug used to
treatosteoporosis, is thought to inhibit the disc degeneration associated with
osteoporosis, the precise mechanism involved remains unclear. In the present
study, primary Sprague-Dawley rat nucleus pulposus cells (NPCs) were cultured,
phenotyped and then treated with dexamethasone (DXM) for 48 h. Cell area analysis
and beta-galactosidase staining were used to investigate the effect of DXM on the
senescence of NPCs. In addition, the protein levels of LC3-II, Beclin-1, P62, p
mTOR and p-p70S6k were determined by western blotting and analyzing the
regulatory effect of PTH upon autophagy and the mTOR signaling pathway in cells
treated with DXM. Following autophagic inhibition induced by ATG5 siRNA
transfection, the regulatory effect of PTH on senescence in NPCs were
investigated in addition to the potential role of autophagy. As the concentration
of DXM increased, the size of the NPCs was significantly enlarged and the
proportion of cells with positive beta-galactosidase staining increased
significantly (P<0.05). In terms of protein expression, PTH treatment led to an
increase in LC3-II and Beclin-1 proteins, a reduction in P62 protein, and
inhibited p-mTOR and p-p70S6k protein expression in DXM-treated NPCs (P<0.05).
PTH attenuated the effect of DXM according to the cell size and percentage of
beta-galactosidase-positive cells. However, the inhibition of autophagy via ATG5
siRNA transfection reversed the protective effect of PTH on cell senescence
(P<0.05). Collectively, the present findings suggest that PTH may inhibit the
senescence of NPCs induced by DXM by activating autophagy via the mTOR pathway.
PMID- 29956815
TI - Upregulation of the Kank1 gene inhibits human lung cancer progression in vitro
and in vivo.
AB - Kank1, an important member of the Kank gene family, plays an important role in
the development of many malignant tumors. As a brand new tumor-suppressor gene,
the expression of Kank1 gene has been revealed to be downregulated or absent in
many malignant tumors. However, there is no study concerning the specific role of
Kank1 in the development and progression of lung cancer. In the present study, we
found that the Kankl gene was significantly downregulated in human lung cancer
and lung cancer cells. When the Kankl gene was upregulated, we found that the
proliferation of lung cancer cells was significantly inhibited, the cells were
arrested in the G0/G1 phase, the apoptosis of cells was observed, the expression
of the caspase family of genes was altered with mainly the activation of caspase
3 and -9, and Bcl-2/Bax ratio was significantly imbalanced. In addition, we also
found that upregulation of the Kankl gene resulted in the inhibition of tumor
cell invasion and metastasis. Concurrently, in vivo nude mice experiments also
confirmed that upregulation of Kank1 expression led to reduced tumor formation in
nude mice and significantly reduced tumor volume. These results revealed that
upregulation of the Kankl gene inhibited the progression of lung cancer both in
vitro and in vivo, and its mechanism was closely related to cell apoptosis as
well as tumor invasion and metastasis.
PMID- 29956814
TI - E-cadherin is downregulated by microenvironmental changes in pancreatic cancer
and induces EMT.
AB - The aim of the present study was to research the effect of microenvironmental
change on epithelial-mesenchymal transition (EMT) in pancreatic cancer cells and
to determine the correlation between E-cadherin expression and the prognosis of
pancreatic cancer patients. We established hypoxic, serum-deficient and TGF-beta
induced microenvironment models of pancreatic cancer cells and studied the
changes in the mRNA and protein expression of EMT-related molecules, E-cadherin
and vimentin, using western blot analysis and real-time PCR. Furthermore,
immunohistochemistry was used to investigate E-cadherin expression in pancreatic
cancer tissues, and survival analysis and COX regression analysis were conducted.
In pancreatic cancer cells under hypoxic, serum-starved and TGF-beta-induced
microenvironments, E-cadherin protein and mRNA levels were significantly
decreased (P<0.05), while vimentin protein and mRNA expression levels were
significantly increased (P<0.05). The results of immunohistochemistry showed that
the protein level of E-cadherin in pancreatic cancer tissues was positively
correlated with overall survival (P<0.01). The results of Cox regression analysis
showed that E-cadherin was an independent prognostic factor in pancreatic cancer.
In conclusion, E-cadherin expression was significantly decreased by
microenvironment changes, and this decrease induced EMT in pancreatic cancer
cells. E-cadherin is an independent prognostic marker in pancreatic cancer
patients.
PMID- 29956816
TI - The role of "after washing imaging" in evaluation of tear drainage system by
dacryoscintigraphy.
AB - BACKGROUND: The aim of this study was to evaluate the efficacy of "after washing"
imaging in interpretation of dacryoscintigraphy as a functional imaging technique
used in evaluation of tearing problems. MATERIALS AND METHODS: 300 nasolacrimal
systems were studied. 100 MUCi of technetium-99m sodium pertechnetate as drops of
activity (10 MUL) were placed into the inferior fornix of each eye. Dynamic
images were obtained for 15 minutes in the sitting position. "After washing"
phase was done by placing a drop (10 MUL) of normal saline in each eye and
external ocular massage for an additional 10 minutes. The imaging patterns for
each eye in the first dynamic phase and after washing phase were recorded,
separately. RESULTS: First dynamic phase demonstrated a sensitivity of 97.4% and
specificity of 22.6%. After washing phase showed a sensitivity of 91.2% and
specificity 75.5%. After washing test, the obstruction pattern changed to "patent
nasolacrimal duct" or "further progression" of the radiotracer to the
nasolacrimal duct in the 25.1% and 24.4% of the nasolacrimal systems,
respectively. CONCLUSIONS: After washing imaging is a useful method in
dacryoscintigraphy which can improve the specificity of scan for diagnosis of
lacrimal duct obstruction. It can also improve the localization of obstruction
level in the lacrimal systems.
PMID- 29956817
TI - Value of planar lymphoscintigraphy (PL) versus SPECT/CT in evaluation of sentinel
lymph node in trunk melanoma - one center, large series retrospective study.
AB - BACKGROUND: Localization and histopathological examination of sentinel lymph node
is a standard of melanoma treatment. The first stage of identification of the SLN
is the preoperative lymphoscintigraphy. The aim of this study was to assess and
compare diagnostic value of planar lymphoscintigraphy and SPECT/CT in sentinel
lymph node biopsy procedure performed in patients with cutaneous trunk melanoma.
MATERIAL AND METHODS: Between 2015 and 2016, patients with trunk melanoma (N =
255, F/M 95/160), aged from 17 to 88 after an excisional biopsy, with primary
tumor >= pT1b (AJCC 2009, median Breslow thickness 2.0 ?+/- 3.13) were included
in the study. In all the patients PL was followed by SPECT/CT 1-3 hours after
injection of 99mTc- colloid particles, and SLNB was performed the next day.
RESULTS: SPECT-CT revealed 78 (18.6%) SLN more than PL, and in 40 patients showed
additional lymph drainage regions leading to surgical adjustments. In 18 patients
(7.1%) SPECT-CT revealed SLN not visible in the PL (false-negative PL) and in 22
patients (8.6%), foci of uptake interpreted in PL as hot SLNs were found to be
non-nodal sites of uptake when assessed on SPECT/CT (false positive PL). SPECT-CT
vs. PL mismatch was observed in 31 patients (12.2%) and was the most common in
patients with primary lesions located in the anterior inferior medial region
(75%). CONCLUSIONS: Results of the presented study indicates the high diagnostic
value of SPECT-CT in assessment of SLNs and proved that SPECT-CT increases the
sensitivity and accuracy of SLN identification as compared to PL even in very
experienced hands.
PMID- 29956818
TI - Simultaneous breast cancer and DLBCL lymphoma - role of PET/CT examination with
18F-FDG and 18F-FES.
AB - Breast cancer is the most common cancer in women in the western world. The
estrogen receptor (ER) is expressed in two thirds of newly diagnosed breast
cancers, so hormonal treatment is performed only in the receptor positive
patients. The most successful ER imaging radiopharmaceutical in PET techniques is
16alpha-[18F]-flouro-17beta-estradiol (18F-FES). The diffuse large B cell
lymphoma (DLBCL) is one of the most common NHL, however, non-Hodgkin lymphoma
constitutes only 4% of all primary cancers in women. The typical staging of
disease is done using 18-fluorodeoksyglukose (18F-FDG) PET/CT.
PMID- 29956819
TI - Neutrophils as myeloid-derived suppressor cells.
AB - Neutrophils form the first line of defence against invading pathogens, such as
bacteria and fungi, as part of the innate immune response. Recently, neutrophils
have also been discovered as repressors of adaptive immune responses. Under
certain conditions, such as cancer and severe injury, an expansion of immature
and mature neutrophils has been observed to induce suppression of T-cell
proliferation. These suppressing cells are known as so-called myeloid-derived
suppressor cells (MDSCs), a heterogeneous population of granulocytic-MDSCs and
monocytic-MDSCs. Initially, MDSCs were believed to be a specific immature type of
myeloid immune cell released from the bone marrow, but mature neutrophils have
also been proposed to have suppressive capacity. However, granulocytic-MDSCs show
a similar morphology and expression of cell surface markers as mature
neutrophils. The only characteristic that discriminates granulocytic (g)-MDSCs
from mature neutrophils is their suppressive capacity, raising the question
whether human g-MDSCs and neutrophils are actually different cell types or
whether they are one plastic cell type that can functionally polarize from
microbial killers to immunosuppressor cells, depending on local conditions. In
this review, we will focus on the MDSC activity of circulating mature
neutrophils.
PMID- 29956820
TI - Increased rate of lumbar spondylolisthesis in rheumatoid arthritis: A case
control study.
AB - OBJECTIVE: The aim of this study was to compare the prevalence of lumbar
spondylolisthesis (SPL) in patients suffering from low back pain (LBP) with or
without rheumatoid arthritis (RA) and to identify potential factors associated
with SPL in patients with RA. METHODS: We performed a case-control study. Cases
and control patients had chronic LBP (more than 4 weeks). Patient with RA
fulfilled the 2010 ACR/EULAR criteria. The main outcome was the presence of
lumbar SPL on lumbar X-ray. The prevalence of SPL between RA and control patients
was compared using chi-squared test. Potential factors associated with SPL in
patients with RA were investigated by univariate and multivariate analysis,
estimating odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A
total of 67 cases and 83 controls were included. Median [interquartile range] age
of patients with RA was 60.0 years [51.0-72.0]; 80.6% were females; and 92.5% and
83.6% were positive for anti-citrullinated protein antibodies (ACPAs) or
rheumatoid factor, respectively. Mean RA disease duration was 11.2 +/- 8.7 years.
SPL was more frequent in patients with RA than controls (41.8% versus 18.1%, P =
0.001). Adjusted to gender, RA was associated with increased prevalence of SPL
(OR 3.15 [95% CI 1.48-6.70], P = 0.003). Among patients with RA, SPL was mainly
Grade 1 (85.7%). Multivariate analysis revealed SPL is associated with increased
age in patients with RA (OR 1.06 [1.02-1.11], P = 0.004). CONCLUSION: In a
population of patients with chronic LBP, the prevalence of lumbar SPL was higher
with than without RA. SPL might be explained by synovitis of lumbar facet joints.
PMID- 29956821
TI - Anatomic description of the palmaris longus muscle and report of variant nerve
supply in the white-footed tamarin (Saguinus leucopus Gunther, 1876).
AB - The gross anatomy of the palmaris longus muscle in 12 specimens of Saguinus
leucopus was studied by dissection. This muscle was constant and unipennate,
originated in the medial epicondyle of the humerus; inserted onto flexor
retinaculum and palmar aponeurosis; and innerved by the median nerve, and in one
case, together with the ulnar nerve. This is the first report of double
innervation for this muscle in primates.
PMID- 29956822
TI - Construction and usability of community health nursing database in rural north
eastern Thailand.
AB - INTRODUCTIONS: Digitization could be incorporated in rural areas of resource-poor
countries because information gathered by nurses working on-site could be better
used. BACKGROUND: For effective management of community health information, the
usage and maintenance of digital records are important. Digitization of
information provides essential information for informing health policy. AIM: To
develop a sustainable database to effectively collect and manage community health
information and nursing practice. METHODS: This study used a mixed method design.
Phase 1 involved the development of a database system through repeated systematic
focus group discussions with community health nurses. Phase 2 involved a
practical trial examination of the developed system with both objective and
subjective evaluations. RESULTS: A nursing database system was developed with
templates designed for the major health problems of communities. The templates
were composed of multiple-choice items and a free-text field that allowed records
to be more detailed than handwritten records and maintained in standardized
formats. This enables accumulation of data that were less likely to be influenced
by the variance of ability in each nurse. DISCUSSION AND CONCLUSION: A
multifaceted evaluation of the database system suggested that it could improve
the efficiency of information management and contribute to the improvement of
nursing care quality through standardization of the recording pattern.
IMPLICATIONS FOR NURSING AND HEALTH POLICY: The nursing database will enable high
quality information storage that will potentially better inform health and
healthcare policies as well as enable visualization of data concerning nursing
care challenges and activities within the relevant communities. This information
is essential for policy development and implementation in areas of human and
fiscal resource allocations and meeting training/education needs.
PMID- 29956824
TI - Terminal 13p deletion in squirrel monkey (Saimiri sciureus) with differentiated
phenotype.
AB - BACKGROUND: The taxonomic classification of squirrel monkeys is often
controversial issue offering many different information. The classification of
captive animals is difficult due to the phenotypic similarities between the
presented species, which is observed mainly in coat coloration. METHODS: The
objective of this study was to analyze the chromosome pattern of one squirrel
monkey with off standard physical characteristics, which is kept in the
Laboratory Animals Breeding Center in Rio de Janeiro State, Brazil, and try to
establish some correlations. Chromosomes were obtained using lymphocyte culture
technique. RESULTS AND CONCLUSIONS: Evaluation of G bands showed a terminal
deletion in one chromosome of pair 13. The association of the results found with
the different phenotypic characteristics led us to classify it as a Saimiri
sciureus specimen with a structural chromosomal change, possibly allowing the
expression of hemizygous alleles.
PMID- 29956823
TI - Impact of patatin-like phospholipase domain containing 3 rs738409 G/G genotype on
hepatic decompensation and mortality in patients with portal hypertension.
AB - BACKGROUND: The rs738409 C>G p.I148M variant in the patatin-like phospholipase
domain containing 3 (PNPLA3)-gene promotes triglyceride accumulation in
hepatocytes and hepatic stellate cell activation and has previously been linked
to hepatic steatosis/liver fibrosis. AIM: To investigate its impact on hepatic
decompensation and (liver-related) mortality in patients who had already
developed portal hypertension. Moreover, we assessed its link with hepatic
steatosis as evaluated by controlled attenuation parameter. METHODS: We performed
a retrospective analysis in prospectively characterised patients with viral
hepatitis/fatty liver disease-induced portal hypertension (hepatic venous
pressure gradient [HVPG] >= 6 mm Hg) diagnosed at the Medical University of
Vienna who underwent HVPG measurement (until 2013; n = 372; longitudinal study)
or simultaneous HVPG and controlled attenuation parameter measurement (2014-2017;
n = 153; cross-sectional study). RESULTS: While survival was similar between
PNPLA3-C/C and -C/G patients, we observed substantially increased mortality in
PNPLA3-G/G patients. PNPLA3-G/G had no impact on mortality in the subgroup of
patients with viral hepatitis; however, we observed a strong independent
association between PNPLA3-G/G and hepatic decompensation (adjusted
subdistribution hazard ratio [aSHR]: 2.1, 95% confidence interval [95% CI]: 1.1
4; P = 0.024) as well as mortality (overall: aSHR: 2.2, 95% CI: 1.22-3.98; P =
0.009; liver-related: aSHR: 2.2, 95% CI: 1.08-4.46; P = 0.029) in patients with
fatty liver disease. Interestingly, even in the subgroup of patients who had
already progressed to clinically significant portal hypertension (HVPG >= 10 mm
Hg), PNPLA3-G/G substantially increased mortality (aSHR: 2.33, 95% CI: 1.27-4.29;
P = 0.006). PNPLA3-genotype had no influence on controlled attenuation parameter
or the prevalence of values >=248 dB/m. CONCLUSION: PNPLA3-G/G-genotype seems to
double the risks of hepatic decompensation and (liver-related) mortality in
patients with portal hypertension due to fatty liver disease. Further studies are
warranted to investigate potential underlying pathophysiological mechanisms
unrelated to hepatic steatosis.
PMID- 29956825
TI - Case management effectiveness for managing chronic illnesses in Korea: a
systematic review.
AB - BACKGROUND: Case management has been adopted in Korea and been recognized as a
promising care-coordination method that lowers costs and improves quality of
care. However, the effectiveness of case management among individuals with
chronic illnesses who reside in the community has yet to be established. AIM:
This systematic review identifies and synthesizes recent evidence of case
management's effectiveness in managing chronic illnesses among adults in Korea.
METHODS: The methodology of this systematic review was guided by the Cochrane
processes and PRISMA statements. A search of multiple bibliographic databases to
identify studies of case management in the populations of Koreans adult with
chronic illnesses was conducted. Studies that met the inclusion criteria were
published in English or Korean. Nine empirical peer-reviewed studies published
between 2008 and 2016 were selected for review. RESULTS: The retrieved studies
show that case management programmes in Korea for adults with chronic illness in
the community were led by nurses. There was strong evidence that nurse-led case
management was effective in improving psychobehavioural and objective clinical
outcomes; however, results for health services utilization outcomes were mixed.
CONCLUSION: In future, research with rigorous study designs and large sample size
in multiple settings are needed to further assess the effectiveness of case
management in Korea. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse-led case
management would be of support in the care of chronic illnesses not only in Korea
but also in Asian countries which share standard practice of case management with
Korea. Nursing leaders should allocate resources to sponsor educational resources
and practical strategies for evidence-based case management.
PMID- 29956826
TI - Acid suppression medications reduce risk of oesophageal adenocarcinoma in
Barrett's oesophagus: a nested case-control study in US male veterans.
AB - BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists
(H2RAs) may reduce the risk of oesophageal adenocarcinoma (OAC) in Barrett's
oesophagus; however, current epidemiologic studies are inconclusive. AIM: To
evaluate the independent effects of PPIs and H2RAs on risk of OAC in patients
with Barrett's oesophagus. METHODS: We conducted a nested case-control study of
male veterans diagnosed with Barrett's oesophagus. Cases with incident OAC were
matched by incidence density sampling on birth year and Barrett's diagnosis date
to controls with Barrett's oesophagus who did not develop OAC. We identified
prescription medication usage 1 year prior to Barrett's oesophagus diagnosis to 3
months prior to the OAC diagnosis. Odds ratios (OR) and 95% CI were estimated
using conditional logistic regression. RESULTS: Compared with 798 controls, the
300 cases were less likely to use PPIs (90.0% vs 94.5%, P = 0.01) and H2RAs
(19.7% vs 25.7%, P = 0.04). In the multivariable model including the use of
statins, H2RAs, aspirin and nonsteroidal anti-inflammatory drugs, PPI use was
associated with 41% lower risk of OAC (OR 0.59, 95% CI 0.35-0.99). While risk
reduction of OAC was stronger for high-dose PPIs (omeprazole daily dose >40 mg,
adjusted OR 0.11, 95% 0.04-0.36), we did not find a dose-response relationship
with PPI duration (P trend = 0.45). Likewise, H2RA use was independently
associated with 30% lower risk of OAC (OR 0.70, 95% CI 0.50-0.99). CONCLUSION:
Use of PPIs and H2RAs among patients with Barrett's oesophagus are associated
with lower risk of OAC. Further clinical trials are needed to confirm this
possible chemopreventive effect.
PMID- 29956827
TI - A baseline tool for predicting response to peginterferon alfa-2a in HBeAg
positive patients with chronic hepatitis B.
AB - BACKGROUND: Peginterferon induces off-treatment responses in approximately one
third of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis
B. AIM: To develop an easy-to-use baseline prediction score to identify hepatitis
B virus (HBV) genotype B-/C-infected HBeAg-positive Asian patients likely to
respond to peginterferon alfa-2a. METHODS: Generalised additive models, multiple
logistic regression (MLR) analysis and internal validation methods were applied
to data from 647 HBeAg-positive patients from China, Hong Kong and Taiwan to
develop a scoring system to predict response 24 weeks after completing a 48-week
course of peginterferon alfa-2a. RESULTS: Five baseline factors (age, sex,
alanine aminotransferase ratio, hepatitis B surface antigen (HBsAg) level and HBV
DNA level) were retained in the final MLR for HBeAg seroconversion and used to
develop a scoring system from 0 to 7. Among patients with scores of 0-1, 2-3, 4
or >=5, HBeAg seroconversion was achieved in 6.4% (6/94), 23.0% (61/265), 36.4%
(67/184) and 54.8% (57/104), respectively, and a combined response (HBeAg
seroconversion plus HBV DNA <2000 IU/mL) in 5.3% (5/94), 12.8% (34/265), 25.0%
(46/184) and 36.5% (38/104), respectively. Among patients with scores of 0-1, 2
3, 4 or >=5, 57.0% (53/93), 12.3% (31/253), 3.4% (6/178) and 1.0% (1/100) had
HBsAg >=20 000 IU/mL at treatment Week 12; only 3/91 (3.3%) with HBsAg >=20 000
IU/mL experienced a combined response at 24 weeks post-treatment (negative
predictive value = 97% [88/91]). CONCLUSION: A pre-treatment scoring system using
readily available baseline characteristics identifies HBeAg-positive Asian
patients likely to experience sustained HBeAg seroconversion after treatment with
peginterferon alfa-2a.
PMID- 29956828
TI - In vivo assay of the potential gadolinium-induced toxicity for sensory hair cells
using a zebrafish animal model.
AB - Recently, intratympanic injection of gadolinium-based contrast agent (GdC) is
growing in use to visualize the endolymphatic hydrops. Although GdC has been
quite safely used over 20 years through intravenous injection, the biological
influence of GdC on sensory hair cells needs to be thoroughly assessed for wider
clinical application of it through intratympanic injection. In this in vivo
experimental study, the summated number of sensory hair cells (SO1, SO2, O1 and
OC1 neuromasts) showed a steep decrease in the group exposed to 10% and 20% GdC
(35.7 +/- 7.3, 15.09 +/- 10.82, respectively, P < .01) compared with the control
group (47.18 +/- 2.30). An increase in apoptosis was also observed in the group
exposed to 20% gadolinium (7.20 +/- 5.56), as compared with the control group
(0.08 +/- 0.72) or the group exposed to 10% gadolinium (3.48 +/- 3.32). A
significant reduction in the viable cytoplasmic mitochondria was observed in
embryos exposed to 20% GdC (369 +/- 124 MUm2 , P = .01) as compared with control
embryos (447 +/- 118 MUm2 ) or embryos exposed to 10% GdC (420 +/- 108 MUm2 ).
GdC administration did not impact peripheral neural structures. GdC caused a
significant reduction in sensory hair cell counts in response to high
concentrations along with increased apoptosis and mitochondrial damage. However,
it may not be likely that GdC will lead to hair cell toxicity, as the estimated
concentration in the inner ear after clinically tried intratympanic injection is
far more diluted than the non-toxic concentration (0.625%) that was tested in
this study.
PMID- 29956829
TI - Emerging role of dental professionals in collaboration with medical personnel in
disaster relief following the 2016 Kumamoto earthquakes: implications for the
expanding scope of dental practice.
PMID- 29956830
TI - Comparing the New and Existing Hypotheses on Energy Metabolism and Longevity.
PMID- 29956831
TI - Visceral leishmaniasis in an infant gorilla (Gorilla gorilla gorilla): Clinical
signs, diagnosis, and successful treatment with single-dose liposomal
amphotericin B.
AB - A 2-year-old captive gorilla (Gorilla gorilla gorilla) was diagnosed with
visceral leishmaniasis in Brazil, and treated with a single dose of liposomal
amphotericin B, which resulted in clinical cure. This is the first report of
visceral leishmaniasis in gorillas, and the first reported liposomal amphotericin
B treatment in great apes.
PMID- 29956832
TI - Simultaneous determination of eight components in Angelica sinensis based on
UHPLC-ESI-MS/MS method for quality evaluation.
AB - A method employing ultra-high performance liquid chromatography-tandem mass
spectrometry (UHPLC-MS/MS) for determination of eight components including
ferulic acid, senkyunolide A, butylphthalide, ligustilide, butylidenephalide,
senkyunolide I, senkyunolide H and levistolide A in Angelica sinensis was
established. The separation was carried out using a Waters ACQUITY UHPLC BEH C18
column with gradient elution with 0.1% formic acid aqueous and acetonitrile at a
flow rate of 0.4 mL/min. Good linearity was attained with R2 of 0.9983-0.9998 in
wide concentration ranges. The method had limit of detection (LOD) and
quantitation (LOQ) in the range of 0.42-6.98 ng/mL and 1.39-23.28 ng/mL,
respectively. Intra- and inter-day precisions varied with relative standard
deviations (RSDs) from 0.33% to 0.88% and 0.37% to 1.04%, respectively. Moreover,
the average recoveries were in a satisfactory range of 92.7%-102.1% with RSDs of
less than 3.60%. Finally, the method was successfully applied to analyze 19
batches of A. sinensis samples grown in Min County, Gansu province, China, as
well as that collected in other regions. The findings indicated that the
established method is reliable and may thus be applied as a powerful tool for
qualitative and quantitative analysis of components in A. sinensis, which has its
implications in quality control of A. sinensis.
PMID- 29956833
TI - Reproductive cycling in adult baboons (Papio species) that were intrauterine
growth restricted at birth implies normal fertility but increased psychosocial
stress.
AB - We investigated menstrual cycles in intrauterine growth restricted (IUGR, 7-10
years, n = 8) and age-matched control (n = 10) baboons. Cycle duration and plasma
anti-Mullerian hormone were similar. IUGR spent more days per cycle swollen and
had elevated early morning fasted serum cortisol, suggesting normal fertility in
the presence of increased psychosocial stress.
PMID- 29956834
TI - Unusual findings on infantile cortical hyperostosis: A case report.
AB - BACKGROUND: Caffey's disease is a rare syndrome, usually self-limiting, affecting
newborn and young infants. On radiological exams, the cortical hyperostosis is
always present, associated or not to soft tissue swelling. Other radiographic
presentations are described as lytic areas. AIM: This article has the objective
to relate computed tomography (CT) findings of Caffey's disease, where lytic
lesion on mandibular angle was the principal radiological manifestation. METHODS
AND RESULTS: Three-dimensional reconstructions were performed to demonstrate the
initial aspect and the healing process. CONCLUSION: This report shows unusual
radiological characteristics of Caffey's disease on CT and its progressive
resolution.
PMID- 29956835
TI - Improved estimates of net primary production, growth, and standing crop of
Macrocystis pyrifera in Southern California.
AB - The giant kelp Macrocystis pyrifera forms subtidal forests on shallow reefs in
temperate regions of the world. It is one of the fastest-growing multicellular
autotrophs on Earth and its high productivity supports diverse marine food webs.
In 2008, we published a method for estimating biomass and net primary production
(NPP) of giant kelp along with five years of data, to provide a more integrated
measure of NPP than those yielded by previous methods. Our method combines
monthly field measurements of standing crop and loss rates with a model of kelp
biomass dynamics to estimate instantaneous mass-specific growth rates and NPP for
each season of each year. We have since improved our approach to account for
several previously unresolved sources of biomass loss. These improvements have
led to a near doubling of our prior estimates of growth and NPP. At our site with
the most persistent stand of giant kelp, NPP averages ~5.2 kg dry mass.m-2 .yr-1
and results from the rapid growth (~3.5% per d) of a relatively small standing
biomass (~0.4 kg dry mass/m2 on average) that turns over ~12 times annually. Here
we provide revised estimates of seasonal biomass, growth, and NPP for the five
years covered by our previous publication (2002-2006), along with more than a
decade of additional data (2007-2017). We also present updated relationships for
predicting giant kelp biomass and NPP from much more easily obtained measurements
of frond density. These data can be used to understand the mechanisms that drive
variation in giant kelp NPP at a wide range of temporal scales. No copyright or
proprietary restrictions are associated with the use of this data set other than
citation of this Data Paper.
PMID- 29956836
TI - Plant growth promoting bacteria associated with corm of Crocus sativus during
three growth stages.
AB - Corm, being a unit of reproduction and storage, plays an indispensable role in
the life cycle of Crocus sativus (saffron). This study deals with the screening
of bacteria isolated from cormosphere (area surrounding the corm sheath) of C.
sativus during three growth stages for biofertilizer and biocontrol property. Out
of 1000 protease producing bacteria isolated from the cormosphere (soil adhering
corm sheath in analogy to rhizosphere), three plant growth promoting (PGP)
Bacilli namely Bacillus thuringiensis DC1, B. megaterium VC3 and B.
amyloliquefaciens DC8 were selected based on multiple and maximum PGP traits
along with corm rot pathogen antagonism. To evaluate in vivo efficacy of the
consortia, pot trials were conducted and a significant increase in number and
length of both, shoot and root were observed. Further, the disease incidence in
test corms was reduced by threefold as compared to control and the number of
daughter corms produced in pot trials was also increased. Since corm is a unit of
reproduction/propagation, increase in its number is of major significance. This
is the first report on isolation and characterization of Plant growth promoting
bacteria from any cormosphere.
PMID- 29956838
TI - Nucleotide-binding and oligomerization domain (NOD)-like receptors in teleost
fish: Current knowledge and future perspectives.
AB - Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are a
group of intracellular pathogen recognition receptors (PRRs) that play key roles
in pathogen recognition and subsequent activation of innate immune signalling
pathways. Expressions of several NLR subfamily members, including NOD1, NOD2, NLR
C3, NLR-C5 and NLR-X1 have been reported in many different teleost fish species.
These receptors are activated by a variety of ligands, including
lipopolysaccharides (LPS), peptidoglycans (PGN) and polyinosinic-polycytidylic
acid [Poly(I:C)]. Synthetic dsRNA and bacterial or viral infections are known to
stimulate these receptors both in vitro and in vivo. In this review, we focus on
the identification, expression and function of teleost NLRs in response to
bacterial or viral pathogens. Additionally, NLR ligand specificity and signalling
pathways involved in the recognition of bacterial or viral stimuli are also
summarized. This review focuses on current knowledge in this area and provides
future perspectives regarding topics in need of additional investigation.
Understanding the response of innate immune system to bacterial or viral
infections in diverse species could inform the development of more effective
therapies and vaccines.
PMID- 29956837
TI - Heat-inactivated Mycobacterium bovis protects zebrafish against mycobacteriosis.
AB - Control of mycobacterial infection constitutes a priority for human and animal
health worldwide. However, effective vaccines are needed for the control of human
and animal tuberculosis (TB). Adult zebrafish have become a useful model for
studying the pathophysiology of mycobacterial infection and for the development
of novel interventions for TB control and prevention. Recently, parenteral and
oral immunization with the heat-inactivated Mycobacterium bovis vaccine (M. bovis
IV) protected wild boar against TB. The objectives of this study were to provide
additional support for the role of M. bovis IV in TB control using the zebrafish
model and to conduct the first trial with this vaccine for the control of fish
mycobacteriosis. The results showed that M. bovis IV protected zebrafish against
mycobacteriosis caused by low and high infection doses of Mycobacterium marinum
and provided evidence suggesting that the protective mechanism elicited by M.
bovis IV in zebrafish as in other species is based on the activation of the
innate immune response through the C3 pathway, with a role for the regulatory
protein Akr2 in this process. These results encourage the use of M. bovis IV for
TB control in different species.
PMID- 29956839
TI - Kin recognition in rice (Oryza sativa) lines.
AB - Kin recognition is an important mediator of interactions within individuals of a
species. Despite increasing evidence of kin recognition in natural plant
populations, relatively little is known about kin recognition in crop species
where numerous cultivars have been generated by artificial selection. We
identified rice (Oryza sativa) cultivars with the ability for kin recognition
from two sets of indica-inbred and indica-hybrid lines at different levels of
genetic relatedness. We then assessed this ability among kin and nonkin and
tested potential mechanisms in a series of controlled experiments and field
trails. Rice cultivars with the ability for kin recognition were capable of
detecting the presence of kin and nonkin and responded to them by altering root
behavior and biomass allocation, particularly for grain yield. Furthermore, we
assessed the role of root exudates and found a root-secreted nitrogen-rich
allantoin component to be responsible for kin recognition in rice lines. Kin
recognition in rice lines mediated by root exudates occurs in a cultivar
dependent manner. Rice cultivars with the ability for kin recognition may
increase grain yield in the presence of kin. Such an improvement of grain yield
by kin recognition of cultivar mixtures offers many implications and applications
in rice production.
PMID- 29956840
TI - MicroRNA-645 promotes metastasis of osteosarcoma via targeting tumor suppressor
NM23 nucleoside diphosphate kinase 2.
AB - Osteosarcoma is the most common non-hematological primary bony malignancy in
children and young adults with tumor metastasis being a common event at
diagnosis. Understanding the pathogenesis of metastatic osteosarcoma may help
identify potential therapeutic targets. In this study, we found that the level of
microRNA-645 (miR-645) in osteosarcoma tumor tissues was significantly increased
compared with their paired non-tumorous tissues, and was associated with
histologic grade, TNM staging, lymph metastasis and distant metastasis. Knockdown
of miR-645 caused a remarkable inhibition of migration of osteosarcoma U2OS
cells. Furthermore, miR-645 inhibited NME2 (nucleoside diphosphate kinase 2)
expression through directly binding to its 3' untranslated region. In human
osteosarcoma tissues, we also found that NME2 was significantly decreased in
tumor tissues, and its level was negatively correlated with miR-645. In addition,
silencing NME2 attenuated the decreased cell migration by knockdown of miR-645,
suggesting that it was involved in the miR-645 induced cell migration of
osteosarcoma cells. Taken together, we found that miR-645 was up-regulated in
osteosarcoma tissues and could promote osteosarcoma cell migration through
directly inhibiting the tumor suppressor NME2. Our data provide novel insight
into the role of miR-645 in osteosarcoma and indicate that miR-645 might be a
potential therapeutic target of osteosarcoma.
PMID- 29956841
TI - Changes in perceived oral health in a longitudinal population-based study.
AB - OBJECTIVES: The aim was to examine whether the changes in different measures of
perceived oral health (POH) were similar and related to each other over 11 years
in the Finnish adult population in a longitudinal setting. Perceived oral health
was measured by means of subjective oral health (SOH), self-assessed treatment
need (STN), and oral health-related quality of life (OHRQoL). METHODS: The data
were collected as part of the nationally representative Health 2000 and Health
2011 (BRIF 8901) surveys on Finnish adults born in 1981 or earlier. SOH and STN
were measured using single items and OHRQoL using the 14-item Oral Health Impact
Profile (OHIP-14). The changes in STN and OHRQoL were reported by age group and
by gender. Age groups (born in 1971 or later, in 1956-1970, in 1946-1955, or in
1945 or earlier) were based on access to subsidized oral health care. General
linear mixed models for changes in perceived oral health variables were
conducted. RESULTS: Subjective oral health and oral health-related quality of
life with impacts occurring occasionally, fairly often, or very often (OFoVo)
showed similar results and remained good or improved in the majority of the
participants. Self-assessed treatment need in the population showed less
consistent results. Subjective oral health was good in the adult population.
About half of the participants, regardless of age and gender, reported self
assessed treatment need in both years, showing a decrease among women and an
increase in the youngest group. Perceived oral health improved significantly in
the two oldest age groups regardless of the measure. The general linear mixed
model revealed that changes in all three perceived oral health variables were
related even when adjusted for age and gender. CONCLUSION: Multiple perceived
oral health measures might be useful for service planning, as the changes in the
three separate measures used in this longitudinal study were various and thus
measured different aspects of perceived oral health. Research including both self
perceived and clinical indicators is needed to understand need for care as a
whole.
PMID- 29956842
TI - Nonsyndromic orofacial clefts among Jews and non-Jews born in 13 hospitals in
Israel during 1993-2005.
AB - OBJECTIVES: Orofacial clefts are one of the most common birth malformations and
represent a significant public health economic expenditure. The purpose of this
investigation was to study the epidemiology of orofacial clefts in newborns from
1993 to 2005 in Israel. In addition, a comparison of data from the National Birth
Defects Registry (NBDR) and Hospital records will be made. METHODS: A
retrospective data review of reports to the Israeli NBDR on infants with
orofacial clefts in comparison with records reviewed at 13 major hospitals,
accounting for 60% of all births in Israel. RESULTS: Of 1334 newborns found to be
with orofacial clefts all over Israel between 1993 and 2005, 1015 were reported
to the NBDR and 319 were unreported but retrieved from hospital files. During
this period, of the 976 578 live births found in the 13 participating hospitals,
there were 866 newborns with orofacial clefts. Of those, 684 (79%) were
nonsyndromic orofacial clefts and 182 (21%) had additional syndromes. The
prevalence of nonsyndromic orofacial clefts was 7/10 000 live births, lower than
reported outside Israel. Only 65% of orofacial clefts retrieved from the 13
hospitals were reported to the NBDR. A significantly higher orofacial cleft
prevalence was found among non-Jews than Jews (11 and 6 of 10 000 live births,
respectively), (P < .00 001). CL/P was found more frequently than isolated cleft
palate (CP). More males had orofacial clefts than females, mostly unilateral with
left side predominance. CONCLUSIONS: The prevalence of nonsyndromic orofacial
clefts was found to be 7/10 000 live births. The higher orofacial cleft
prevalence among non-Jews may be explained by the high prevalence of
consanguinity and deprived maternal nutritional status in this population.
PMID- 29956844
TI - Acute electrophysiologic effects of the polyphenols resveratrol and piceatannol
in rabbit atria.
AB - The natural polyphenol resveratrol and its analogue piceatannol have various
beneficial effects including antiarrhythmic properties. The aim of the present
study was to examine potential electrophysiologic effects in an experimental
whole-heart model of atrial fibrillation (AF). Simultaneous infusion of
resveratrol (50MUM) or piceatannol (10MUM) in rabbit hearts resulted in an
increase of atrial refractory period. Both agents induced a significant slowing
of atrial conduction and of intrinsic heart rate. In both groups, a trend towards
a reduction of AF and a regularization of AF was observed. This article is
protected by copyright. All rights reserved.
PMID- 29956843
TI - Ephenidine, diphenidine, and methoxphenidine complications reported to the French
Addictovigilance Network.
AB - Ephenidine, diphenidine, and methoxphenidine belong to the family of
diarylethylamines that are psychoactive substances derived from lefetamine (N, N
di-methyl-1,2-diphenylethylamine, also called L-SPA). These dissociative
anesthetic compounds act as potent and selective N-methyl-d-aspartate receptor
antagonists and were recently classified as narcotic drugs in France. The
available data suggest a significant risk of psychic and somatic complications.
To obtain more information, this retrospective study analyzed all spontaneous
notifications of serious cases of ephenidine, diphenidine, and methoxphenidine
abuse collected by the French Addictovigilance Network from 2012 to 2016 and
classified them as proven, probable, and possible. For each case, age, sex,
concomitantly ingested substances, pattern of abuse of psychoactive drugs, and
related complications (scored using the poisoning severity score) were collected.
Eighteen cases were identified (one in 2013, five in 2015, and 12 in 2016) in 16
men (median age: 31.5 years [IQR 25-75% 27-34]). Ephenidine, diphenidine, and
methoxphenidine were involved in four, seven, and 11 cases, respectively. No case
was considered proven, 16 cases were considered possible, and two probable due to
polysubstance abuse (co-ingestion of other new psychoactive substances). The
reported clinical complications were minor in five cases, moderate in six cases,
and serious in four cases, and included psychiatric, neurologic, and
cardiovascular problems. This analysis indicates that the number of reported
cases progressively increased from 2012 to 2016 and mainly concerned
methoxphenidine. The addictive potential of these substances seems highly
probable; but further investigations are needed to limit their harmful effects.
PMID- 29956846
TI - Tungsten Borides: On the Reaction of Tungsten with Boron(III) Bromide.
AB - The crucible-free reaction between heated tungsten wires and gaseous boron
tribromide yields different tungsten borides. The experiments were carried out at
various reaction temperatures and times, revealing the formation of W2 B, WB and
WB2 phases. The underlying reactions were analyzed by using thermodynamic model
calculations. The stability of the gaseous tungsten bromides was evaluated using
quantum chemical methods. While the developed synthesis of phase-pure borides is
only possible to a limited extent, it offers a potential route for a formation of
protective coatings with high chemical and thermal resistance.
PMID- 29956845
TI - Can bone marrow cellularity help in predicting prognosis in myelodysplastic
syndromes?
AB - OBJECTIVES: To ascertain the relevance of bone marrow cellularity (BMC) to the
interpretation of blast percentage (blast%) in MDS prognostication. METHODS: We
compared survival prediction based on blast% adjusted to different levels of
cellularity, compared to the survival based on the original IPSS-R blast%
grouping. RESULTS: We analyzed 355 consecutive MDS patients. Cellularity, in and
of itself or its interaction with blast%, was not associated with overall
survival (OS). In a small subset of patients with a hypercellular marrow (15%; n
= 26), dismal prognosis was observed at lower levels of blast%. For these cases
OS was similar to higher IPSS-R blast groups. For example, within the
Intermediate group (blast% 5%-10%), those with a hypercellular marrow and >6%
blasts had an OS of 10 m similar to 16 m in the High (blast% 10%-19%) blast
group. These changes did not translate into a significant improvement in overall
prognostic power of a cellularity-adjusted IPSS-R (C index 0.71 vs. 0.70).
CONCLUSION: Adjusting blast% to cellularity did not improve prognostication.
However, within IPSS-R-defined blast groups, a small subset of patients with
relatively higher blast% and hypercellularity may have a worse prognosis than
expected.
PMID- 29956847
TI - Anti-TNF-alpha therapy modulates mTORC1 signalling in hidradenitis suppurativa.
PMID- 29956848
TI - SMYD1 is the underlying gene for the AnWj-negative blood group phenotype.
AB - BACKGROUND: AnWj is a high-incidence blood group antigen associated with three
clinical disorders: lymphoid malignancies, immunologic disorders, and autoimmune
hemolytic anemia. The aim of this study was to determine the genetic basis of an
inherited AnWj-negative phenotype. METHODS: We identified a consanguineous family
with two AnWj-negative siblings and 4 additional AnWj-negative individuals
without known familial relationship to the index family. We performed exome
sequencing in search for rare homozygous variants shared by the two AnWj-negative
siblings of the index family and searched for these variants in the four non
related AnWj-negative individuals. RESULTS: Exome sequencing revealed seven
candidate genes that showed complete segregation in the index family and for
which the two AnWj-negative siblings were homozygous. However, the four
additional non-related AnWj-negative subjects were homozygous for only one of
these variants, rs114851602 (R320Q) in the SMYD1 gene. Considering the frequency
of the minor allele, the chance of randomly finding 4 consecutive such
individuals is 2.56 * 10-18 . CONCLUSION: We present genetic and statistical
evidence that the R320Q substitution in SMYD1 underlies an inherited form of the
AnWj-negative blood group phenotype. The mechanism by which the mutation leads to
this phenotype remains to be determined.
PMID- 29956849
TI - Stereocontrolled Photoinduced Electron Transfer in Metal-Fullerene Hybrids.
AB - Photoinduced electron transfer in transition-metal complexes linked to a
fullerene moiety is of increasing interest. Recently, several stereoisomers of an
Ir-complex exhibiting configurational stability at metal center, which does not
undergo epimerization have been synthesized (Angew. Chem. Int. Ed. 2017, 56,
2136). The presence of multiple electron donor and acceptor sites located at
opposite ends with respect to the metallic center creates the prerequisites for
the formation of entirely different charge transfer (CT) states. Here we report
the results of quantum mechanical calculations and detailed analysis of excited
state properties for all stereoisomers of the junction. We found that the
stereoisomers demonstrate clearly different CT properties by photoexcitation. The
found photo-stereospecific effects can be used to design new hybrids with a
different type of photoinduced CT state, exhibiting dissimilar activity in
photocatalysis.
PMID- 29956850
TI - Predictors of plate extrusion in oromandibular free flap reconstruction.
AB - OBJECTIVES: Plate extrusions after free tissue transfer for mandibular
reconstruction can be problematic and generally require revision surgery. Our
objective was to assess the predictors of plate extrusion and compare outcomes
between fibular free flaps (FFF), lateral border scapular flaps (LBSF), and
scapular tip free flaps (STFF). METHODS: Retrospective review of consecutive
patients who underwent osseous free tissue reconstruction of the mandible (2008
2014) at Victoria Hospital, London, Ontario. Patient demographics and treatment
related information were collected. RESULTS: We identified 134 procedures and 27
(20.2%) plate extrusions (21/61 FFF, 3/49 STFF, and 3/24 LBSF). Freedom from
extrusion after 2 years was significantly associated with the use of FFF (P =
.003, HR 6.09 1.82-20.44), performing 1 osteotomy (P = .03, HR 2.61 1.08-6.31),
and anterior mandibular defects (P = .01, HR 2.66 1.25-5.66) in the univariate
model. FFF's were employed more frequently in younger patients, with 2.4 mm
plates, more anterior defects, and with a greater number of osteotomies (P <
.001). However, after controlling for these variables in multivariate analyses
the use of a FFF was the only significant predictor of extrusion at 2 years (P =
.006, HR 3.68 1.46-9.28). CONCLUSIONS: At our institution, use of the STFF
predicts mandibular defects that are less prone to developing plate extrusion and
FFF tended to be used more frequently in anterior defects with osteotomies.
However, after controlling for these factors use of the FFF appeared to have
higher rates of extrusion than scapular flaps. Further prospective studies
controlling for defect variables are needed to elucidate the risk factors for
plate extrusion.
PMID- 29956851
TI - Fifty years of osteochondrosis.
PMID- 29956852
TI - Tooth loss is a complex measure of oral disease: Determinants and methodological
considerations.
AB - OBJECTIVES: Counts of missing teeth or measures of incident tooth loss are
gaining attention as a simple way to measure dental status in large population
studies. We explore the meaning of these metrics and how missing teeth might
influence other measures of dental status. METHODS: An observational study was
performed in 2 contrasting adult populations. In total, 62 522 adult participants
were available with clinically assessed caries and periodontal indices from the
Swedish arm of the Gene-Lifestyle Interactions and Dental Endpoints Study (GLIDE)
and the Korea National Health and Nutrition Examination Survey (KNHANES) in the
Republic of Korea. Longitudinal measures of tooth loss were available for 28 244
participants in GLIDE with median follow-up of 10.6 years. RESULTS: In
longitudinal analysis, hazard for tooth loss was associated with baseline dental
status (previous tooth loss, periodontal status and caries status) and socio
demographic variables (age, smoking status and highest educational level).
Analysis of cross-sectional data suggested that indices of caries exposure were
not independent of periodontal status. The strength and direction of association
varied between groups, even for measures specifically intended to avoid measuring
tooth loss. Individuals with impaired periodontal health (community periodontal
index [CPI] 3 or higher in any sextant) had higher standardized decayed and
filled surfaces (DFS; number of DFS divided by total number of tooth surfaces) in
GLIDE (incidence risk ratio [IRR] 1.05 [95% CI: 1.04, 1.07], but lower
standardized DFS in KNHANES (IRR: 0.95 [0.92, 0.98]) than individuals with better
periodontal health (CPI <3 in all sextants). CONCLUSIONS: Incident tooth loss is
a complex measure of dental disease, with multiple determinants. The relative
importance of dental caries and periodontal disease as drivers of tooth loss
differs between age groups. Measures of dental caries exposure are associated
with periodontal status in the studied populations, and these associations can be
population-specific. Consideration of the study-specific properties of these
metrics may be required for valid inference in large population studies.
PMID- 29956853
TI - Chemical Kinetics of Radiolabelling Reactions.
AB - The application of chemical kinetics is one of the most powerful and versatile
tools for investigating reaction mechanisms in complex mixtures. Kinetic studies
are commonplace in traditional synthetic chemistry but are seldom used in
radiopharmaceutical sciences. When deriving standard reaction rate laws, the
focus is normally placed on calculating the chemical concentration of different
species over time. In radiopharmaceutical synthesis, the desired product is one
of the radioactive components of the mixture. Reaction conditions are optimised
to obtain the radioactive product in the highest activity yield. When short-lived
radionuclides are used, radioactive decay during the reaction window means that
the maximum activity yield does not necessarily coincide with the chemical or
decay-corrected radiochemical yields. To account for this difference in the
kinetic models, it is shown how standard integrated rate laws can be modified to
incorporate the contribution from radioactive decay. An example is then presented
to show how radiochemical kinetics can be used to model complex systems, like [18
F]FDG radiosynthesis, that involve parallel or competing reactions at the
different chemical scales of the radionuclide and substrate. Increased knowledge
of reaction rates, and a more wide-spread application of radiochemical kinetics,
can facilitate the development of new radiolabelling reactions. Accurate
identification of maximum activity yields using kinetic models also has the
potential to improve the optimisation and radiochemical efficiency of all current
and future radiopharmaceutical syntheses.
PMID- 29956854
TI - Great Barrier Reef recovery through multiple interventions.
AB - The decline of coral cover on Australia's Great Barrier Reef (GBR) has largely
been attributed to the cumulative pressures of tropical cyclones, temperature
induced coral bleaching, and predation by crown-of-thorns starfish (CoTS). In
such a complex system, the effectiveness of any management intervention will
become apparent only over decadal time scales. Systems modeling approaches are
therefore essential to formulating and testing alternative management strategies.
For a network of reefs, we developed a metacommunity model that incorporated the
cumulative pressures of tropical cyclones, coral bleaching, predation, and
competition between corals. We then tested the response of coral cover to
management interventions including catchment restoration to reduce discharge onto
the reef during cyclone-induced flood events and enhanced protection of trophic
networks supporting predation of CoTS. Model results showed good agreement with
long-term monitoring of the GBR, including cyclical outbreaks of CoTS driven by
predator-prey dynamics on the network of reefs. Testing of intervention
strategies showed that catchment restoration would likely improve coral cover.
However, strategies that combined catchment restoration with enhanced CoTS
predation were far more effective than catchment restoration alone.
PMID- 29956855
TI - Pulmonary arterial hypertension in patient treated for multiple sclerosis with 4
aminopyridine.
AB - 4-Aminopyridine (4-AP) is a recent treatment indicated to improve walking in
patient with multiple sclerosis. We report the first case of pulmonary arterial
hypertension (PAH) that we attribute to the use of 4-AP. A 64-year-old woman with
multiple sclerosis presented with dyspnea. After excluding other secondary causes
of pulmonary hypertension, a diagnosis of severe PAH due to 4-AP was made based
on right heart catheterization. History revealed that the dyspnea began with the
initiation of 4-AP. After discontinuation of 4-AP therapy and initiation of
ambrisentan and tadalafil, dyspnea and pulmonary arterial pressure have improved
significantly and one specific PAH treatment was stopped. 4-AP is an outward
rectifying potassium channel blocker with a vasoconstrictor effect in animal's
pulmonary artery. According to the chronological sequence of events, the lack of
other etiology, and its pharmacological plausibility, 4-AP is highly suspected to
have induced our patient's PAH.
PMID- 29956856
TI - Cellular and epigenetic changes induced by heat stress in bovine preimplantation
embryos.
AB - Exposure of the preimplantation embryo to heat stress triggers a series of
cellular, molecular, and adaptive changes preventing a normal embryonic
development. Heat stress disrupts the embryo cytoskeleton, intracellular calcium
levels, mitochondrial function, and induces apoptosis. Moreover, heat stress can
act indirectly through induction of reactive oxygen species (ROS), leading to a
variety of cellular damage. Embryonic resistance to heat shock is determined by
factors such as genotype, developmental stage, apoptosis, redox status, and
regulatory molecules. The early embryo is very susceptible to heat stress; it
acquires resistance to elevated temperature as development advances. One of the
mechanisms involved in the developmental acquisition of thermotolerance is heat
induced apoptosis, which acts as a quality control mechanism to remove damaged
blastomeres allowing the embryo to survive after stress. Although embryos at >8
cell stage can activate the apoptotic cascade as an adaptive response to stress,
embryos at the two-cell stage are resistant to proapoptotic signals. This lack of
apoptotic response has been associated to mitochondrial resistance to
depolarization and epigenetic regulations, such as DNA methylation and histone
deacetylation. Even though the cellular mechanisms triggered by heat stress have
been studied, very little attention has been paid to the vulnerability of the
epigenome to drastic temperature changes during the preimplantation period.
Therefore, this review aims to characterize the effects of elevated temperature
on the bovine embryo, especially addresissing developmental, cellular, and
epigenetic alterations triggered in response to temperature.
PMID- 29956857
TI - Raspberry bodies and hyaline globules with positive napsin A immunoexpression are
useful features in diagnosing clear cell carcinoma of the female genital tract in
cytology samples.
PMID- 29956858
TI - " La cuisson? A point s'il vous plait! ": Medium or well done?
PMID- 29956859
TI - Factors associated with referral offer and acceptance following supportive care
problem identification in a comprehensive cancer service.
AB - To improve understanding of the triage process following distress and problem
identification and the factors associated with offer and acceptance of supportive
care referrals. Review of patient records/charts at a metropolitan hospital in
Melbourne, Australia. Data were collected on problem identifications from 1/1/13
to 30/6/14, including patient demographics, disease and treatment information,
responses to the NCCN Distress Thermometer (DT) and Problem Checklist (PC),
whether referrals to supportive care services were offered and accepted/declined.
Logistic regressions examined factors associated with referral offer and
acceptance. Of patients completing the DT/PC, 50.1% reported a high level of
distress. Overall, 61% of patients were offered referral(s), with the majority
(71%) being accepted. Referrals were more likely to be offered to patients with a
greater number of problems (Odds Ratio[OR] = 1.18, 95%CI = 1.12-1.25) and higher
distress (OR = 1.68, 95%CI = 1.07-2.64). Referrals were more likely to be
accepted by patients with a greater number of problems (OR = 1.12, 95%CI = 1.06
1.19) and lower distress (OR = 0.58, 95%CI = 0.34-1.00). The type of problem
experienced by the patient was strongly related to the type of referral they were
offered. At a large metropolitan hospital with in-house supportive care services,
simple problem identification with the DT/PC enabled triage to services that
reflected patients' needs. The findings suggest that clear referral pathways and
an organisational emphasis on supportive care may facilitate service use.
PMID- 29956860
TI - Assessment of patient understanding of their medicines: interviews with community
dwelling older Australians.
AB - OBJECTIVE: To identify patterns of medication load, client's care team,
coordination of healthcare and clients' understanding of their medications.
METHODS: Face-to-face interviews were conducted with community-dwelling older
Australians between June and August 2017 in three community pharmacies in
Adelaide, South Australia. KEY FINDINGS: Forty interviews were conducted. On
average, participants were taking 7.53 medicines with 77.5% using five or more
regularly. Lack of collaboration between healthcare professionals, need for
increased communication between prescribers and increased patient education on
medicines, were highlighted. This study demonstrates that polypharmacy and
inappropriate prescribing are occurring within the community pharmacy setting,
but shows insight into how these concerns can be overcome, by implementing
pharmacist-led services such as non-dispensing pharmacists in community
pharmacies. CONCLUSION: Careful consideration when prescribing and effective
communication are required to minimise risks associated with polypharmacy in this
population.
PMID- 29956862
TI - Graft-versus-host disease-like erythroderma: a manifestation of thymoma
associated multiorgan autoimmunity.
PMID- 29956861
TI - Swallow strength training exercise for elderly: A health maintenance need.
AB - BACKGROUND: Recent studies have shown high prevalence of oropharyngeal dysphagia
associated with frailty- and age-related muscle weakness. Strength training
exercises have been advocated for locomotive health maintenance in the elderly
and have shown positive outcomes. As muscles involved in oropharyngeal phase of
swallowing are also comprised of striated muscles, the aim of this study was to
determine biomechanical effect of a novel resistance exercise program, Swallowing
Against Laryngeal Restriction (SALR), on pharyngeal phase swallowing in the
healthy elderly. METHODS: A total of 28 volunteers (75 + 7 years; 17 females)
with no complaint of dysphagia were studied using video fluoroscopy before and
after 6 weeks of the swallow strength training exercise. Eighteen of these
volunteers also underwent high-resolution pharyngeal manometry non-concurrent
with fluoroscopy. Ten additional volunteers (81 + 6 years; 9 females) were
studied by videofluoroscopy before and after 6 weeks of a sham exercise. KEY
RESULTS: Swallow resistance exercise but not the sham exercise resulted in a
significant increase in maximum upper esophageal sphincter opening (P < .01),
superior and anterior laryngeal excursion (P < .01) as well as posterior
pharyngeal wall thickness (P < .01). Resistance exercise but not sham exercise
also resulted in a significant increase in deglutitive pharyngeal contractile
integral (P < .01). CONCLUSIONS & INFERENCES: Strength training of muscles
involved in the pharyngeal phase of swallowing using the swallowing against
laryngeal restriction technique is feasible and significantly improves key
physiologic features of the pharyngeal phase of swallowing. These findings
provide the basis for consideration of developing an exercise-based swallow
health maintenance program for the elderly swallow health maintenance program for
the elderly.
PMID- 29956864
TI - Stage T3b prostate cancer diagnosed by seminal vesicle biopsy and treated with
neoadjuvant hormone therapy, permanent brachytherapy and external beam
radiotherapy.
AB - OBJECTIVES: To report the long-term results of prostate brachytherapy followed by
external beam radiotherapy (EBRT) in men with a positive seminal vesicle biopsy
(+SVB). PATIENTS AND METHODS: In all, 1081 men with localised prostate cancer
were treated with permanent brachytherapy, of which 615 had staging SVB and 53
(9.4%) were positive. Higher stage, Gleason score and PSA level were associated
with a +SVB (P < 0.001). Patients with +SVB and negative laparoscopic pelvic
lymph node dissection, bone and CT scans had 3 months of androgen-deprivation
therapy (ADT) followed by 103 Pd implant to the prostate (dose 100 Gy) and
proximal SVs, and 2 months later 45 Gy EBRT. ADT was continued for a median of 6
months (total ADT 9 months). The mean (range) follow-up was 9 (5-22) years.
RESULTS: Biochemical freedom from failure (computed by the Phoenix definition),
freedom from metastasis, and cause-specific survival (CSS) for patients with a
negative SVB (-SVB) vs +SVB at 15 years, was 76.3% vs 60.6% (P = 0.001), 95.4% vs
78.2% (P < 0.001), and 95% vs 70.4% (P < 0.001), respectively. Prostate cancer
death occurred in 45 of 590 (7.6%) men with a -SVB vs eight of 25 (32%) with a
+SVB (odds ratio 5.7, 95% confidence interval 2.35-13.9, P < 0.001). Cox
proportion hazard rates (HRs) demonstrated Gleason score (P < 0.001, HR 1.9),
stage (P = 0.010, HR 1.42), RT dose (P = 0.013, HR 0.991), and +SVB (P = 0.001,
HR 4.48), as significantly associated with CSS. CONCLUSIONS: Men with a +SVB have
inferior CSS compared to those with a -SVB. However, a strategy that included a
SVB in high-risk patients and implantation of the SVs in men undergoing combined
therapy still yields favourable long-term results.
PMID- 29956865
TI - Macrophages are a source of IL-17 in the human placenta.
AB - PROBLEM: To determine if placental macrophages (Hofbauer cells) can synthesize
and secrete cytokines of the IL-17 family throughout pregnancy and to reveal the
patterns of cytokine expression in early and late gestation. METHODS OF STUDY:
Macrophages were isolated from the first-trimester and term placental villous
tissues from normal pregnancies. Basal and stimulated intracellular production of
IL-17A, IL-17E, IL-17F as well as IL-17A secretion was quantified by flow
cytometry and cytometric bead array, respectively. The expression of IL-17 and IL
23 receptors was determined on the surface of the placental macrophages by flow
cytometry after antibody staining. RESULTS: In early and late gestation, a
substantial proportion of the placental macrophages synthesized IL-17A and IL
17F, but not IL-17E, as determined by intracellular staining of the cytokines.
Neither the intracellular production nor the secretion of IL-17 was significantly
affected by LPS stimulation and spontaneous labour. The level of secretion
decreased slightly but significantly at term. The IL-23 receptor was absent on
the surface of cells, whereas variable expression of the IL-17 receptor was
observed. CONCLUSION: Placental macrophages constitutively produced IL-17 at
different gestational ages and represent thus a source of this cytokine in the
human placenta. Patterns of the cytokine and receptor expression suggest that
this cell population may participate in non-immune processes and contribute to
the regulation of placental development and function.
PMID- 29956866
TI - Utilizing state-of-the-art "omics" technology and bioinformatics to identify new
biological mechanisms and biomarkers for coronary artery disease.
AB - Identification of the four standard modifiable cardiovascular risk factors
(SMuRFs)-diabetes mellitus, hyperlipidaemia, hypertension, and cigarette smoking
has allowed the development of risk scores. These have been used in conjunction
with primary and secondary prevention strategies targeting SMuRFs to reduce the
burden of CAD. Recent studies show that up to 25% of ACS patients do not have any
SMuRFs. Thus, SMuRFs do not explain the entire burden of CAD. There appears to be
variation at the individual level rendering some individuals relatively
susceptible or resilient to developing atherosclerosis. Important disease
pathways remain to be discovered, and there is renewed enthusiasm to discover
novel biomarkers, biological mechanisms, and therapeutic targets for
atherosclerosis. Two broad approaches are being taken: traditional approaches
investigating known candidate pathways and unbiased omics approaches. We review
recent progress in the field and discuss opportunities made possible by
technological and data science advances. Developments in network analytics and
machine learning algorithms used in conjunction with large-scale multi-omic
platforms have the potential to uncover biological networks that may not have
been identifiable using traditional approaches. These approaches are useful for
both biomedical research and precision medicine strategies.
PMID- 29956867
TI - Perirenal fat surface area as a risk factor for perioperative difficulties and 30
day postoperative complications in elective colon cancer surgery.
AB - AIM: Visceral obesity is associated with perioperative and postoperative
complications in colorectal surgery. We aimed to investigate the association
between the perirenal fat surface area (PRF) and postoperative complications.
METHOD: Data on 610 patients undergoing curative, elective colon cancer resection
between 2006 and 2016 at Stockholm South General Hospital were retrieved from a
local quality register. We assessed perioperative and postoperative outcomes
using a multinomial regression model adjusted for age, sex, American Society of
Anesthesiologists classification and surgical approach (open/laparoscopy) in
relation to PRF. RESULTS: PRF could be measured in 605 patients; the median area
was 24 cm2 . Patients with PRF >= 40 cm2 had longer operation time (median 223 vs
184 min), more intra-operative bleeding (250 vs 125 ml), reoperations (11% vs
6%), surgical complications (27% vs 13%) and nonsurgical infectious complications
(16% vs 9%) than patients with PRF < 40 cm2 , but there were no differences in
the need for intensive care or duration of hospital stay. The multivariate
analyses revealed an increased risk of any complication [OR 1.68 (95% CI 1.1
2.6)], which was even more pronounced for moderate complications [Clavien-Dindo
II, OR 2.14 (CI 1.2-2.4]; Clavien-Dindo III, OR 2.35 (CI 1.0-5.5)] in patients
with PRF >= 40 vs < 40 cm2 . The absolute risk of complications was similar in
men and women with PRF >= 40 cm2 . CONCLUSION: PRF, an easily measured indirect
marker of visceral obesity, was associated with overall and moderate
complications in men and women and could serve as a useful tool in the assessment
of preoperative risk.
PMID- 29956868
TI - Plant community response to switchgrass (Panicum virgatum) population source in
establishing prairies.
AB - Ecological restoration and revegetation efforts entail the translocation of
native plant populations. Risks associated with these efforts include failure of
translocated populations to establish or, conversely, such strong establishment
that they excessively dominate the recipient community. The role that selective
breeding plays in mediating these risks is unclear but of increasing importance
as efforts to restore and establish multifunctional grasslands also increase. In
a three-year, spatially replicated study, we seeded experimental prairie
communities with either domesticated (cultivar) or undomesticated strains of
Panicum virgatum (switchgrass), a North American C4 species under development as
a biomass crop. We evaluated the composition, performance, and diversity of the
recipient plant communities and compared the performance of cultivar and
undomesticated switchgrass in those communities. We found little evidence that
switchgrass population source affected community response. Switchgrass cultivars
modestly exceeded undomesticated strains with respect to stand establishment,
third-year stand density, and aboveground biomass; effect size and significance
differed among sites. Our results suggest that including cultivars in ecological
restorations and multifunctional grasslands may enhance success of switchgrass
establishment with little risk of impairing the composition or diversity of plant
communities for up to three years, as reflected in the measures used here.
However, the incorporation of undomesticated switchgrass into multifunctional
grasslands may enhance landscape-scale genetic variation and mitigate risks
associated with gene flow between translocated and local wild switchgrass
populations; more research on these dynamics is needed.
PMID- 29956869
TI - Stem cell characteristics and the therapeutic potential of amniotic epithelial
cells.
AB - Multiple stem cell types can be isolated from the human placenta. Recent advances
in stem cell biology have revealed that human amniotic epithelial cells (hAECs)
are one of the perinatal stem cells which possess embryonic stem cell-like
differentiation capability and adult stem cell-like immunomodulatory properties.
Unlike other types of placental stem cells, hAECs are derived from pluripotent
epiblasts and maintain multilineage differentiation potential throughout
gestation. Similar to mesenchymal stem cells, hAECs are also able to modulate the
local immune response. These, and other properties, make hAECs attractive for
cellular therapy. This review article summarizes current knowledge of stem cell
characteristics and immunomodulatory properties of amniotic epithelial cells and
aims to advance our understanding towards the goal of novel therapy development.
PMID- 29956870
TI - Satisfaction rate at 1-year follow-up in patients treated with penile implants:
data from the multicentre prospective registry INSIST-ED.
AB - OBJECTIVES: To investigate scores and predictors of patient satisfaction at 1
year after penile prosthesis implantation (PPI) using the validated Quality of
Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire. PATIENTS AND
METHODS: Analyses were performed for 142 patients prospectively included in the
national multicentre registry Italian Nationwide Systematic Inventarization of
Surgical Treatment for Erectile Dysfunction (INSIST-ED), which provided 1-year
follow-up data. Postoperative patient satisfaction was assessed using the
validated QoLSPP tool. Linear logistic regression analyses assessed predictors of
QoLSPP total and single domain scores, including age at surgery, erectile
dysfunction aetiology, type of prosthesis, surgical approach, surgeon experience
and complications. Locally weighted regression methods were used to explore the
relationship between surgeon experience and QoLSPP scores. RESULTS: Overall, high
median functional, relational, social, personal and total QoLSPP scores were
reported at 1 year after PPI. Patients implanted with hydraulic devices had
higher functional (23 vs 21.5; P = 0.01) and total scores (68 vs 65.5; P = 0.03)
than those with a malleable prosthesis. Surgeon experience emerged as the only
independent predictor of higher satisfaction scores, depicting a non-linear
association with both QoLSPP total and single domain scores (all P < 0.03). Data
suggested that the higher the number of procedures per year, the greater the
satisfaction scores, reaching a plateau after l5 procedures/year. CONCLUSIONS:
This study reports high functional and patient satisfaction scores at 1 year
after PPI surgery using a dedicated tool for the first time. Better outcomes
should be expected for patients treated by surgeons with greater experience.
PMID- 29956871
TI - Expression analysis of extracellular microRNA in bronchoalveolar lavage fluid
from patients with pulmonary sarcoidosis.
AB - BACKGROUND AND OBJECTIVE: MicroRNA (miRNA) are transcriptional regulators
implicated in pulmonary sarcoidosis and packaged in extracellular vesicles (EV)
during cellular communication. We characterized EV and investigated miRNA
expression in bronchoalveolar lavage (BAL) fluid from sarcoidosis patients.
METHODS: EV were characterized for size(s) using dynamic light scattering and
transmission electron microscopy (TEM) analysis and protein markers by
immunoblotting. Twelve extracellular and 5 cellular miRNA were investigated in
BAL from 16 chest X-ray stage-I (CXR-I) and 17 CXR stage-II (CXR-II) sarcoidosis
patients. Associations between miRNA and disease characteristics (extrapulmonary
involvement, pulmonary function and BAL cell profile) were statistically
analysed. RESULTS: BAL from sarcoidosis patients contained exosomes and
microvesicles (MV) as EV. In these EV, expression of miR-146a (P = 0.007), miR
150 (P = 0.003) and BAL cellular miR-21 (P = 0.01) was increased in CXR-II
compared with CXR-I. Other detected EV (miR-21 and miR-26a) and cellular (miR-31,
miR-129-3p, miR-146a and miR-452) miRNA were not differentially expressed. The
investigated miRNA did not reflect extrapulmonary involvement, but EV miR-146a
and miR-150 were negatively correlated with pulmonary function (miR-146a with
vital capacity (VC; Spearman's correlation coefficient (rs ), P = -0.657, 0.007),
percent predicted forced expiratory volume in 1 s (FEV1 ; -0.662, 0.006) and FEV1
/forced vital capacity (FVC) ratio (-0.649, 0.008); miR-150 correlated negatively
with VC (-0.584, 0.019) and FEV1 /FVC ratio (-0.746, 0.001) in CXR-II cases).
CONCLUSION: Our data provide evidence that exosomes and microvesicles as
extracellular vesicles are present in the bronchoalveolar space of sarcoidosis
patients and they differentially express EV miRNA (miR-146a and miR-150), the
expression of which correlates negatively with pulmonary function indices. The
significance of these findings for disease pathophysiology and clinical course
require further investigation.
PMID- 29956872
TI - Level of readiness of chronic pain patients to practise active self-care.
AB - BACKGROUND: Given the limited alleviation of chronic pain with pharmacological
treatments, various nonpharmacological and self-care approaches are often
proposed that require patients' motivation. OBJECTIVE: To evaluate the level of
readiness (LOR) to practise different types of active self-care among chronic
pain patients. METHOD: A quantitative cross-sectional survey was conducted among
all chronic pain patients seeking care at the Pain Center of an academic hospital
from June 2013 to March 2015. Sociodemographic data, pain characteristics,
treatments and the LOR to practise active self-care were investigated. RESULTS:
Among the 1524 eligible patients, 639 (41.9%) were included. The median pain
duration was 8.5 years (interquartile range = 7.5). Two-thirds (63.7%) of the
patients reported high pain-related disability, and 64.6% had used opioids during
the previous six months. Most patients had a high (44.1%) or moderate (24.6%) LOR
to practise active self-care. Multivariable multinomial regression analysis
showed that independent factors associated with a high LOR were a higher level of
education (relative risk ratio (RRR) = 3.42, 95% confidence interval (CI): 1.90
6.13, p < 0.001), unemployed status due to medical condition (RRR = 2.92, 95% CI:
1.30-6.56, p = 0.009), the use of dietary supplements 'against pain' (RRR = 2.77,
95% CI: 1.52-5.04, p = 0.001) and neuropathic pain characteristics (RRR = 1.80,
95% CI: 1.40-3.12, p = 0.036). Older age was a factor predicting a lower LOR (RRR
= 0.97, 95% CI: 0.94-0.99, p = 0.039). Long-term chronic pain, severe pain
related disability and the presence of a mood disorder were not associated with a
lower LOR. CONCLUSION: Most chronic pain patients, including those severely
affected, indicated their readiness to practise active self-care methods.
SIGNIFICANCE: Most chronic pain patients, even those severely affected, appeared
to be ready to practise active self-care therapies and we believe that further
studies are needed to investigate their impact on pain and quality of life.
PMID- 29956873
TI - Guilt among husband caregivers of Chinese women with breast cancer: The roles of
male gender-role norm, caregiving burden and coping processes.
AB - Caregiver guilt (i.e., feeling of inadequacy in providing care to patients) is
commonly experienced and studied among husbands of breast cancer survivors in
Western countries. However, little is known about the psychosocial correlates of
caregiver guilt in their Chinese counterparts. A total of 176 husbands of Chinese
breast cancer survivors completed a cross-sectional survey in Weifang, Shandong
province, China. As expected, hierarchical regression results showed that higher
caregiving burden was associated with higher levels of caregiver guilt. However,
for those who had stronger endorsement of the "Masculinity strength" gender-role
norm, higher seeking social support from spouse was associated with higher guilt;
for those with higher levels of marital satisfaction, higher protective buffering
(i.e., hiding of concerns and negative emotions to protect others) was associated
with lower caregiver guilt. Western assumptions on the harm of protective
buffering and the benefits of support seeking as well as related supportive
evidence among Western populations do not directly apply to the Chinese culture,
which should be brought awareness to research and practice. Practitioners should
consider the cultural background of the caregivers and should not simply
encourage support seeking and discourage protective buffering.
PMID- 29956874
TI - Reliability of arterial stiffness indices at rest and following a single bout of
moderate-intensity exercise in older adults.
AB - Short-term changes in arterial stiffness with exercise are proposed to better
reflect vascular impairments than resting measures alone and are suggested as a
prognostic indicator of cardiovascular risk in older adults. Arterial stiffness
indices are reliable at rest, but the time-course and reliability of postexercise
changes in arterial stiffness in older adults are unknown. The precision of
postexercise changes in arterial stiffness should be determined prior to their
use in large prospective trials. This study assessed the between-day reliability
of the changes in pulse wave velocity (PWV), augmentation index (AIx75) and
reflection magnitude (RM) following an exercise bout in older adults. Ten older
adults (71 +/- 5 years) were tested on three separate days, 7 days apart. PWV,
AIx75 and RM were assessed at rest, immediately post and at 20, 40 and 60 min
during recovery after moderate-intensity cycling. Intraclass correlation
coefficient (ICC) and reliability coefficient (RC) were used to assess the
relative and absolute reliability of arterial stiffness responses. PWV increased,
and RM decreased immediately after exercise (P<0.05), and returned to baseline
during recovery. AIx decreased during recovery (P<0.001). Resting ICC values were
0.91 (PWV), 0.72 (AIx75) and 0.40 (RM). Reliability of the immediate changes
following exercise was high for PWV (ICC:0.87, RC:1.9 m s-1 ) and moderate for
AIx75 (ICC:0.64, RC:7%) and RM (ICC:0.59, RC:9%). Reliability of the postexercise
responses was similar to that at rest for all measures of arterial stiffness.
These findings indicate that postexercise changes in arterial stiffness indices
are reliable in healthy older adults and supports further investigation of the
prognostic value of these responses.
PMID- 29956875
TI - Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes.
AB - BACKGROUND: Whether metformin may reduce hepatocellular carcinoma (HCC) risk
requires confirmation. METHODS: Type 2 diabetes patients newly diagnosed during
1999-2005 and with 2 or more prescriptions of antidiabetic drugs were enrolled
from the Taiwan's National Health Insurance database. A total of 173 917 ever
users and 21 900 never-users of metformin were identified (unmatched cohort). A
1:1 matched-pair cohort of 21 900 ever-users and 21 900 never-users based on a
propensity score (PS) was created. Hazard ratios were estimated by Cox regression
incorporated with the inverse probability of treatment weighting using the PS. In
addition, interactions with aspirin and statin were evaluated. RESULTS: In the
unmatched cohort, 619 never-users and 2642 ever-users developed HCC, with a
respective incidence of 668.0 and 330.7 per 100 000 person-years and an overall
hazard ratio of 0.49 (95% confidence interval: 0.45-0.54). The hazard ratios for
the first (<25.7 months), second (25.7-56.9 months) and third (>56.9 months)
tertile of cumulative duration of metformin therapy were 0.89 (0.81-0.98), 0.50
(0.46-0.56) and 0.23 (0.21-0.26) respectively. Analyses of the matched cohort
showed an overall hazard ratio of 0.76 (0.67-0.85), and the hazard ratios for the
respective tertiles were 1.39 (1.19-1.62), 0.77 (0.65-0.91) and 0.37 (0.30-0.45).
Aspirin and statin were observed to have a significant interaction with
metformin. CONCLUSIONS: Metformin was associated with a reduced risk of HCC in a
dose-response pattern. Users of both metformin and aspirin or metformin and
statin had the lowest risk.
PMID- 29956876
TI - Embedding 1D Conducting Channels into 3D Isoporous Polymer Films for High
Performance Humidity Sensing.
AB - Isoporous block copolymer (BCP) films have received exponential interest as
highly selective membranes, stemming from their unique morphological features,
but their applications in functional devices remain to be realized. Now single
walled carbon nanotubes (CNTs) were efficiently incorporated into isoporous block
copolymer films for chemiresistive sensing at room temperature. Leveraging the
efficient charge extraction ability of CNTs together with nanochannel arrays
aligned perpendicular to the surface of the films, an ultrafast response time of
0.3 s was achieved for humidity detection with a sensor response of about 800 on
changing humidity from 10 % to 95 %. Furthermore, the sensor also responds to
various organic vapors, underscoring its promising detection capability.
PMID- 29956878
TI - Recognition of Complex Core-Fucosylated N-Glycans by a Mini Lectin.
AB - The mini fungal lectin PhoSL was recombinantly produced and characterized.
Despite a length of only 40 amino acids, PhoSL exclusively recognizes N-glycans
with alpha1,6-linked fucose. Core fucosylation influences the intrinsic
properties and bioactivities of mammalian N-glycoproteins and its level is linked
to various cancers. Thus, PhoSL serves as a promising tool for glycoprofiling.
Without structural precedence, the crystal structure was solved using the zinc
anomalous signal, and revealed an interlaced trimer creating a novel protein fold
termed beta-prism III. Three biantennary core-fucosylated N-glycan azides of 8 to
12 sugars were cocrystallized with PhoSL. The resulting highly resolved
structures gave a detailed view on how the exclusive recognition of alpha1,6
fucosylated N-glycans by such a small protein occurs. This work also provided a
protein consensus motif for the observed specificity as well as a glimpse into N
glycan flexibility upon binding.
PMID- 29956877
TI - Regiospecific N-Arylation of Aliphatic Amines under Mild and Metal-Free Reaction
Conditions.
AB - A transition metal-free N-arylation of primary and secondary amines with
diaryliodonium salts is presented. Both acyclic and cyclic amines are well
tolerated, providing a large set of N-alkyl anilines. The methodology is
unprecedented among metal-free methods in terms of amine scope, the ability to
transfer both electron-withdrawing and electron-donating aryl groups, and
efficient use of resources, as excess substrate or reagents are not required.
PMID- 29956880
TI - Application of Claisen Rearrangement and Olefin Metathesis in Organic Synthesis.
AB - Several new synthetic methods to diverse polycycles and heterocycles on the basis
of [3,3]-sigmatropic rearrangement and ring-closing metathesis as key steps are
summarized. In this regard, Claisen, aza-Claisen, and Overman rearrangements are
used in combination with other popular reactions such as ring-closing metathesis,
Suzuki coupling, Diels-Alder reaction, and retro-Diels-Alder reaction. To this
end, we prepared polycycles (e.g., cyclophanes, cage molecules), heterocycles
(e.g., oxepins, azapins), carbocycles, and spirocycles with the use of the above
protocol.
PMID- 29956881
TI - Modular One-Step Three-Component Synthesis of Tetrahydroisoquinolines Using a
Catellani Strategy.
AB - Reported is a modular one-step three-component synthesis of
tetrahydroisoquinolines using a Catellani strategy. This process exploits
aziridines as the alkylating reagents, through palladium/norbornene cooperative
catalysis, to enable a Catellani/Heck/aza-Michael addition cascade. This mild,
chemoselective, and scalable protocol has broad substrate scope (43 examples, up
to 90 % yield). The most striking feature of this protocol is the excellent
regioselectivity and diastereoselectivity observed for 2-alkyl- and 2-aryl
substituted aziridines to access 1,3-cis-substituted and 1,4-cis-substituted
tetrahydroisoquinolines, respectively. Moreover, this is a versatile process with
high step and atom economy.
PMID- 29956879
TI - The factors associated with impulse control behaviors in Parkinson's disease: A 2
year longitudinal retrospective cohort study.
AB - INTRODUCTION: Impulse control behaviors (ICBs) are impulsive-compulsive behaviors
often associated with dopamine replacement therapy in Parkinson's disease (PD).
Although remission can occur in ICB, only four reports on the ratio of remission
and the persistence of ICB have been published, and the associated factors with
ICB remission or persistence have been little known. Therefore, we conducted a
longitudinal assessment of the remission, persistence, and development of ICB and
those associated factors in patients with PD. METHODS: We retrospectively
investigated a PD database at Aomori Prefectural Central Hospital, Japan. One
hundred and forty-eight patients with PD who could be followed up for 2 years
were enrolled. ICB was assessed using the Questionnaire for Impulsive-Compulsive
Disorders in Parkinson's disease. Motor severity (Hoehn and Yahr scale and United
Parkinson's Disease Rating Scale), cognitive function (Mini-Mental State
Examination), and other clinical variables (sex, age, onset age, disease
duration, olfactory dysfunction, and dyskinesia) and medications used to treat PD
were assessed. Univariate analyses were performed. RESULTS: Seven patients were
excluded because of the exclusion criteria, and 141 patients were analyzed.
Thirty patients (21.3%) had ICB at baseline, and these patients also had
significantly higher use of pergolide. The ICB remission rate was 60%, the ICB
persistence ratio was 40%, and the ICB development ratio was 12.6% over 2 years.
Statistically, younger age and pergolide use were associated with ICB
persistence. Being male, having dyskinesia, and rotigotine, entacapone,
zonisamide, and istradefylline use were associated with ICB development.
CONCLUSION: This study suggests that younger age and pergolide use may be the new
associated factors with ICB persistence and that entacapone, zonisamide, and
istradefylline use may be associated with the development of ICB. Drug profiles
and medication practices in Japan may explain the association of these factors
with ICB.
PMID- 29956882
TI - Sex-based differences in antiretroviral therapy initiation, switching and
treatment interruptions: global overview from the International Epidemiologic
Databases to Evaluate AIDS (IeDEA).
AB - INTRODUCTION: In 2015, the World Health Organization recommended that all HIV
infected individuals consider ART initiation as soon as possible after diagnosis.
Sex differences in choice of initial ART regimen, indications for switching, time
to switching and choice of second-line regimens have not been well described. The
aims of this study were to describe first-line ART and CD4 count at ART
initiation by sex, calendar year and region, and to analyse time to change or
interruption in first-line ART, according to sex in each region. METHODS:
Participating cohorts included: Southern, East and West Africa (IeDEA-Africa),
North America (NA-ACCORD), Caribbean, Central/South America (CCASAnet) and Asia
Pacific including Australia (IeDEA Asia-Pacific). The primary outcomes analysed
for each region and according to sex were choice of initial ART, time to
switching and time to discontinuation of the first-line regimen. RESULTS AND
DISCUSSION: The combined cohort data set comprised of 715,252 participants across
seven regions from low- to high-income settings. The median CD4 count at
treatment initiation was lower in men compared with women in nearly all regions
and time periods. Women from North America and Southern Africa were more likely
to switch ART compared to men (p < 0.001) with approximately 90% of women
reporting a major change after 10 years in North America. Overall, after 8 years
on ART, >50% of HIV- positive men and women from Southern Africa, East Africa,
South and Central America remained on their original regimen. Men were more
likely to have a treatment interruption compared with women in low- and middle
income countries from the Asia/Pacific region (p < 0.001) as were men from
Southern Africa (p < 0.001). Greater than 75% of men and women did not report a
treatment interruption after 10 years on ART from all regions except North
America and Southern Africa. CONCLUSIONS: There are regional variations in the
ART regimen commenced at baseline and rates of major change and treatment
interruption according to sex. Some of this is likely to reflect changes in local
and international antiretroviral guideline recommendations but other sex-specific
factors such as pregnancy may contribute to these differences.
PMID- 29956883
TI - Baseline Plasma Cell Gene Signature Predicts Improvement in Systemic Sclerosis
Skin Scores Following Treatment With Inebilizumab (MEDI-551) and Correlates With
Disease Activity in Systemic Lupus Erythematosus and Chronic Obstructive
Pulmonary Disease.
AB - OBJECTIVE: B cells impact the progression of systemic sclerosis (SSc;
scleroderma) through multiple pathogenic mechanisms. CD19 inhibition in mice
reduced skin thickness, collagen production, and autoantibody levels, consistent
with CD19 expression on plasma cells (PCs), the source of antibody production. PC
depletion could effectively reduce collagen deposition and inflammation in SSc;
therefore, we investigated the effects of PC depletion on SSc disease activity.
METHODS: A PC gene signature was evaluated in SSc skin biopsy samples in 2 phase
I clinical trials. We assessed microarray data from tissue from public studies of
chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis
(IPF), dermatomyositis (DM), systemic lupus erythematosus (SLE), and atopic
dermatitis, as well as blood from a phase IIb clinical trial in SLE. RESULTS: The
PC signature was elevated in SSc skin specimens compared to healthy donor skin (P
= 2.28 * 10-6 ) and correlated with the baseline modified Rodnan skin thickness
score (MRSS) (r = 0.64, P = 0.0004). Patients with a high PC signature at
baseline showed greater improvement in the MRSS (mean +/- SD change 35 +/- 16%; P
= 6.30 * 10-4 ) following anti-CD19 treatment with inebilizumab (MEDI-551) than
did patients with a low PC signature at baseline (mean +/- SD change 8 +/- 12%; P
= 0.104). The PC signature was overexpressed in tissue from patients with SLE,
DM, COPD, interstitial lung disease, and IPF relative to controls (all fold
change >2; P < 0.001). The PC signature also differed significantly between SLE
patients with mild-to-moderate disease and those with severe disease (SLE Disease
Activity Index cutoff at 10) (fold change 1.44; P = 3.90 * 10-3 ) and correlated
significantly with the degree of emphysema in COPD (r = 0.53, P = 7.55 * 10-8 ).
CONCLUSION: Our results support the notion that PCs have a role in the
pathogenesis of SSc and other autoimmune or pulmonary indications. An elevated
pretreatment PC signature was associated with increased benefit from MEDI-551 in
SSc.
PMID- 29956885
TI - Discovery of a New Class of Inhibitors of Vaccinia Virus Based on (-)-Borneol
from Abies sibirica and (+)-Camphor.
AB - A series of the bornyl ester/amide derivatives with N-containing heterocycles
were designed and synthesized as vaccinia virus (VV) inhibitors. Bioassay results
showed that among the designed compounds, derivatives 6, 13, 14, 34, 36 and 37
showed the best inhibitory activity against VV with the IC50 values of 12.9,
17.9, 3.4, 2.5, 12.5 and 7.5 MUm, respectively, and good cytotoxicity. The
primary structure-activity relationship (SAR) study suggested that the
combination of a saturated N-heterocycle, such as morpholine or 4
methylpiperidine, and a 1,7,7-trimethylbicyclo[2.2.1]heptane scaffold was
favorable for antiviral activity.
PMID- 29956884
TI - Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world
results from an expanded access programme.
AB - OBJECTIVE: To report the safety and efficacy results of patients enrolled in the
Italian Nivolumab Renal Cell Cancer Expanded Access Programme. PATIENTS AND
METHODS: Patients with metastatic renal cell cancer (mRCC) previously treated
with agents targeting the vascular endothelial growth factor pathway were
eligible to receive nivolumab 3 mg/kg once every 2 weeks. Patients included in
the analysis had received >=1 dose of nivolumab and were monitored for adverse
events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0.
RESULTS: A total of 389 patients were enrolled between July 2015 and April 2016,
of whom 18% were aged >=75 years, 6.7% had non-clear cell RCC, 49.6% had bone and
8.2% brain metastases, and 79% had received >=2 previous lines of therapy. The
most common any-grade treatment-related AEs were fatigue (13%) and rash (9%).
Twenty-two patients (5.7%) discontinued treatment because of AEs. There were no
treatment-related deaths. The objective response rate was 23.1%. At a median
follow-up of 12 months, the median progression-free survival was 4.5 months (95%
confidence interval 3.7-6.2) and the 12-month overall survival rate was 63%.
Similar survival rates were reported among patients with non-clear-cell
histology, elderly patients, those with bone and/or brain metastases, and those
who had received prior first-line sunitinib or pazopanib, or prior everolimus.
CONCLUSION: The safety and efficacy observed were consistent with those reported
in the pivotal Checkmate 025 trial. Results in patients with non-clear-cell mRCC
who were elderly, pretreated with everolimus, and had bone and/or brain
metastases encourage the use of nivolumab in these categories of patients.
PMID- 29956886
TI - Cardiovascular Benefits of Phenol-Enriched Virgin Olive Oils: New Insights from
the Virgin Olive Oil and HDL Functionality (VOHF) Study.
AB - SCOPE: The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF)
study and other related studies on the effect of phenol-enriched virgin olive oil
(VOO) supplementation on cardiovascular disease are integrated in the present
work. METHODS AND RESULTS: VOHF assessed whether VOOs, enriched with their own
phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and
functionality of HDL. In this randomized, double-blind, crossover, and controlled
trial, 33 hypercholesterolemic subjects received a control VOO (80 mg kg-1 ),
FVOO (500 mg kg-1 ), and FVOOT (500 mg kg-1 ; 1:1) for 3 weeks. Both functional
VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat
soluble antioxidants, improving HDL subclasses distribution, reducing the
lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes,
protecting DNA from oxidation, ameliorating endothelial function, and increasing
fecal microbial metabolic activity. Additional cardioprotective benefits were
observed according to phenol source and content in the phenol-enriched VOOs.
These insights support the beneficial effects of OO and PC from different
sources. CONCLUSION: Novel therapeutic strategies should increase HDL-cholesterol
levels and enhance HDL functionality. The tailoring of phenol-enriched VOOs is an
interesting and useful strategy for enhancing the functional quality of HDL, and
thus, it can be used as a complementary tool for the management of
hypercholesterolemic individuals.
PMID- 29956887
TI - Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and
[1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors.
AB - 2-(1-{4-[(4-Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide (3) was
exploited as a starting material for the synthesis of two novel series of 5
arylazo-2-hydrazonothiazoles 6a - 6j and 2-hydrazono[1,3,4]thiadiazoles 10a -
10d, incorporating sulfonamide group, through its reactions with appropriate
hydrazonoyl halides. The structures of the newly synthesized products were
confirmed by spectral and elemental analyses. Also, the antimicrobial,
anticancer, and DHFR inhibition potency for two series of thiazoles and
[1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and
SAR analysis.
PMID- 29956888
TI - Peroxisome-targeted Supramolecular Nanoprobes Assembled with Pyrene-labelled
Peptide Amphiphiles.
AB - Despite the versatile metabolic functions of peroxisomes such as lipid synthesis
and fatty acid oxidation and their relevance to genetically inherited diseases,
namely, peroxisome biogenesis disorders and peroxisomal enzyme deficiency, there
is not much research on peroxisome-targeting therapeutics. Herein we present
supramolecular nanostructured probes based on the self-assembly of peptide
amphiphiles (PAs) having peroxisome-targeting ability in mammalian cells. The PA
was designed to include the peroxisome-targeting tripeptide (SKL) and a
fluorescent dye (pyrene). It was revealed that the presence of the SKL-appended
carboxyl terminal group of PA, the extent of alpha-helical nature of the peptide
block, and the fibrillar morphology of nano-assemblies affected the targeting
efficiency of PA supramolecular nanoprobe. The simple modification of PAs by the
peroxisome-targeting strength prediction showed an enhanced peroxisome
specificity, as expected. This work provides important insights into designing
subcellular organelle-targeting nanoparticles for next-generation nanomedicines.
PMID- 29956889
TI - Auto-Crosslinked Rigid Foams Derived from Biorefinery Byproducts.
AB - A new macroporous foam-like material is presented based on autocross-linking
humins, an industrial biorefinery byproduct. Humins foams are obtained by a
simple heating process, without any pretreatment and with high control of
morphology, porosity, and carbon content. Untreated humins have been
characterized by GC, ultra-performance liquid chromatography (UPLC), elemental
analysis, and FTIR, whereas the mechanism of foaming was elucidated by a
combination of thermal and rheological analyses. A preliminary screening of
conditions was conducted to identify the parameters controlling this foaming
process. A foam was produced in a controlled way with open and/or closed cells
with cell diameters between 0.2 and 3.5 mm. Humins foams were characterized by
Raman spectroscopy, FTIR, SEM, nitrogen adsorption, pycnometry, and mechanical
tests. The results show that, based on humins, it is possible to obtain porous
materials with controlled architectures and a range of parameters that can be
tailored, depending on the foreseen applications.
PMID- 29956890
TI - A realist qualitative study to explore how low-income pregnant women use Healthy
Start food vouchers.
AB - Healthy Start is the UK government's food voucher programme for low-income
pregnant women and young children. It was introduced in 2006, but the impact of
the programme on nutritional outcomes remains understudied. This study sought to
explore potential outcomes of the Healthy Start programme (including intended and
unintended outcomes) and develop explanations for how and why these outcomes
might occur. A realist review preceded this study, in which programme theories
were developed and tested using existing evidence. This qualitative study aimed
to further refine and consolidate the programme theories from the realist review
while remaining open to new and emerging theories (or hypotheses) about how low
income pregnant women use Healthy Start vouchers. Semistructured interviews were
conducted with 11 low-income women from North West England, who received Healthy
Start vouchers during pregnancy. A realist logic of analysis was applied to
generate clear and transparent linkages between outcomes and explanations. The
findings suggested that some women used the vouchers to improve their diets
during pregnancy (intended outcome), whereas some women were diverted towards
alternative or unintended outcomes. Women's circumstances, values, beliefs, and
motivations influenced how they perceived and responded to the vouchers. This
paper presents four evidence-based programme theories to explain four contrasting
(and potentially overlapping) outcomes: dietary improvements (theory refined from
review), shared benefits (new theory), financial assistance (theory refined from
review), and stockpiling formula (new theory). It considers how the Healthy Start
programme could be improved, to increase the possibilities for low-income women
to experience the intended outcome of dietary improvements.
PMID- 29956891
TI - Chemical Composition, Cytotoxic and Antibacterial Activities of Essential Oils of
Cultivated Clones of Juniperus communis and Wild Juniperus Species.
AB - Needles of seven cultivated clones (C1 - C7) of Juniperus communis at lower
altitude and three wild Juniperus species (J. communis, J. recurva and J. indica)
at higher altitudes were investigated comparatively for their essential oils
(EOs) yields, chemical composition, cytotoxic and antibacterial activities. The
EOs yields varied from 0.26 to 0.56% (v/w) among samples. Sixty-one volatile
components were identified by gas chromatography-mass spectrometry (GC/MS) and
quantified using gas chromatography GC (FID) representing 82.5 - 95.7% of the
total oil. Monoterpene hydrocarbons (49.1 - 82.8%) dominated in all samples
(alpha-pinene, limonene and sabinene as major components). Principal component
analysis (PCA) of GC data revealed that wild and cultivated Juniperus species are
highly distinct due to variation in chemical composition. J. communis (wild
species) displayed cytotoxicity against SiHa (human cervical cancer), A549 (human
lung carcinoma) and A431 (human skin carcinoma) cells (66.4 +/- 2.2%, 74.4 +/-
1.4% and 57.4 +/- 4.0%), respectively, at 200 MUg/ml. EOs exhibited better
antibacterial activity against Gram-positive bacteria than against Gram-negative
bacteria with the highest zone of inhibition against Staphylococcus aureus MTCC
96 (19.2 +/- 0.7) by clone-7. As per the conclusion of the findings, EOs of clone
2, clone-5 and clone-7 can be suggested to the growers of lower altitude, as
there is more possibility of uses of these EOs in food and medicinal
preparations.
PMID- 29956892
TI - Surrogate-based visualization and sensitivity analysis of coronary stent
performance: A study on the influence of geometric design.
AB - The main goal of this numerical study is to assess the impact of geometric design
perturbations on the performance of a representative coronary stent platform. In
this context, first, a design parameterization model was defined for the stent
under study. After, a set of metrics characterizing stent performance, namely,
vessel injury, radial recoil, bending resistance, longitudinal resistance, radial
strength, the risk of fracture, prolapse index, and dogboning were evaluated
within the context of a finite element analysis. Afterwards, accurate surrogate
models were developed, using the efficient global optimization algorithm, as
predictive tools in the execution of tasks that normally require a high number of
model evaluations, such as global sensitivity analysis and visualization. In the
end, the dependence of the output response surfaces on the geometric parameters
was mechanically interpreted, which allowed us to understand the complex
interplay that exists between the considered design variables and the defined
performance metrics.
PMID- 29956893
TI - Exploration of predictive metabolic factors for gestational diabetes mellitus in
Japanese women using metabolomic analysis.
AB - AIMS/INTRODUCTION: We aimed to explore novel predictive markers for gestational
diabetes mellitus using metabolomic analysis in pregnant Japanese women.
MATERIALS AND METHODS: We carried out a case-control study with a cohort of
participants enrolled during the first or early second trimester in the Center of
Chiba Unit of the Japan Environment and Children's Study. Participants were
classified as either gestational diabetes mellitus cases or matched controls
based on age, body mass index and parity. Metabolite levels of their serum and
urine obtained randomly before the diagnosis of gestational diabetes mellitus
were analyzed using hydrophilic interaction chromatography tandem mass
spectrometry. Orthogonal projections to latent structures discriminant analysis
was carried out to investigate metabolome profiles for the different groups.
Metabolites with a variable importance in projection value of >1.5 were
identified as potential markers. RESULTS: In total, 242 participants were
enrolled in the study, of which 121 were cases. The R2X, R2Y and Q2 parameters
for the discrimination ability of the resulting models were 0.388, 0.492 and 0.45
for serum, and 0.454, 0.674 and 0.483 for urine, respectively. We finally
identified three metabolites in serum and 20 in urine as potential biomarkers.
Glutamine in serum and ethanolamine and 1,3-diphosphoglycerate in urine showed
>0.8 area under the receiver operating characteristic curves. CONCLUSIONS: The
present study identified serum and urine metabolites that are possible predictive
markers of subsequent gestational diabetes mellitus in Japanese women. Further
studies are required to elucidate their efficacy.
PMID- 29956894
TI - Mental fatigue and impaired cognitive function after an acquired brain injury.
AB - OBJECTIVE: Mental fatigue is a common subjective symptom following an acquired
brain injury. In many cases, this is long-lasting with a considerable negative
impact on work, studies, social activities, and quality of life. No objective
test for mental fatigue exists today. The aim of this study was to investigate
whether mental fatigue can be objectively measured. MATERIALS AND METHODS: This
study included 32 controls with no mental fatigue and 42 well-rehabilitated
participants who suffered from long-term mental fatigue following stroke,
traumatic brain injury, encephalitis or meningitis, and late effects after brain
tumor. Attention, processing speed and working memory were assessed using a test
and retest design following a demanding reading exercise. RESULTS: Significant
interactions were found for tests measuring processing speed, working memory, and
attention. The control group improved at the second test, while those who
suffered from mental fatigue did not. CONCLUSIONS: This study indicates impaired
cognitive performance over time after cognitive activity for individuals
suffering from mental fatigue after an acquired brain injury.
PMID- 29956895
TI - Gualoupi (Pericarpium Trichosanthis) injection in combination with convention
therapy for the treatment of angina pectoris: a Meta-analysis.
AB - OBJECTIVE: To use a Meta-analysis to review the efficacy and safety of Gualoupi
(Pericarpium Trichosanthis)injection (PTI) in the treatment of angina pectoris.
METHODS: We searched the available literature up to January 2015 using Chinese
National KnowledgeInfrastructure (CNKI), Chinese Scientific Journal Database
(VIP), the Wanfang database, PubMed andother English language databases to
identify randomized controlled trials of PTI for the treatment ofangina pectoris.
Two reviewers independently retrieved and extracted the information. Software
ReviewManager 5.3 was used for statistics analysis. RESULTS: Fourteen studies
involving 1621 patients were identified. Compared with conventional therapyalone
or conventional therapy plus other Traditional Chinese Injections (TCMIs), PTI
plus conventionaltherapy significantly improved clinical efficacy [odds ratio
(OR) = 3.56, 95% confidence interval(CI) (2.65, 4.77)] (based on 14 studies),
electrocardiograph efficacy [OR = 3.20, 95% CI (2.26, 4.51)](based on 7 studies),
and efficacy for Traditional Chinese Medicine Syndromes [OR = 3.13, 95% CI(1.43,
6.89)] (based on 3 studies). Moreover, compared with conventional therapy alone
or conventionaltherapy plus other TCMIs, PTI plus conventional therapy
significantly decreased the levels ofplasma viscosity [mean difference (MD) = -
0.47, 95% CI (- 0.76, - 0.17)] (based on 3 studies), andplasma low-density
lipoprotein [MD = -0.94, 95% CI (-1.57, -0.30)] (based on 3 studies). Eleven
studiesreported some mild adverse reactions, and no serious adverse drug
reactions were observed. CONCLUSION: PTI was found to be effective and safe for
the treatment of angina pectoris. This studyhad certain limitations; thus, more
rigorously designed, multi-center, randomized controlled trialsin larger
populations should be performed to support this observation.
PMID- 29956897
TI - Sini decoction as an adjuvant therapy for angina pectoris: a systematic review of
randomized controlled trials.
AB - OBJECTIVE: To systematically assess the effects and safety of Sini decoction as
an adjuvant therapyfor patients with angina pectoris. METHODS: We searched
PubMed, Excerpt Medica Database, the Cochrane library, Wanfang Database,China
National Knowledge Infrastructure Database, China Science and Technology Journal
Databasefrom the date of its inception until August 1, in 2014. Available
literatures were selected accordingto the inclusion criteria. Two reviewers
finished data extraction, checked the data and assessed themethodological quality
of studies, independently. The Review Manage Software 5.1.0 was used for
dataanalysis. RESULTS: Six trials involving 453 participants were eligible. None
of the trials reported the mortalitydue to angina pectoris. The secondary
outcomes showed that Sini decoction, together with nitroglycerinwhen necessary,
may have some effects on reducing the number of angina attacks and theamount of
nitroglycerin. But in terms of reducing the duration of angina and improvement of
electrocardiogram,there were no statistical differences between Sini decoction
group and isosorbide dinitrategroup. Only one reported that no adverse events
were found. CONCLUSION: Based on this systematic review, Sini decoction can
reduce the dosage of nitroglycerin,when compared with isosorbide dinitrate group.
And there were no enough evidence in the papersto draw any conclusions for the
safety of Sini decoction.
PMID- 29956896
TI - Role of Pneumocystis jirovecii in patients with different pulmonary underlying
condition using a nested-PCR.
AB - OBJECTIVE: The prevalence of Pneumocystis jirovecii colonization and its role in
pulmonary disease remains unclear. PCR methods have shown an improved sensitivity
in the detection of this fungus. It has been suggested that the PCR results be
combined with another test such as IFA to create a diagnostic algorithm. METHODS:
A multiplex nested-PCR procedure with a 16S rRNA gene as the internal
amplification control was evaluated to determine the role of P. jirovecii in
pulmonary disease. RESULTS: A 20% of the 199 bronchoalveolar lavage samples were
PCR-positive, 13.5% samples were PCR-inhibited, and the rate of Pneumocystis
colonisation was 6.4%. The sensitivity, specificity, positive predictive value
and negative predictive value of the nested-PCR were 100%, 93%, 70% and 100%,
respectively. The sensitivity of the nested-PCR was higher than the current "gold
standard" immunofluorescence assay (IFA) (p< 0.0001). PCR-negative and PCR
positive patients did not show any clinical or radiological differences in the
medical variables studied. CONCLUSIONS: PCR could help the diagnosis of
Pneumocystis pulmonary disease given the high negative predictive value of the
technique. P. jirovecii DNA can frequently be detected in healthy population, so
the analysis of the patient medical history is critical to make the correct
clinical decision.
PMID- 29956898
TI - Effect of Guizhi Gancao Longgu Muli Tang on sleep disturbances in menopausal
women.
AB - OBJECTIVE: To evaluate the effect of Guizhi Gancao Longgu Muli Tang (GGLMT), a
decoction preparedwith herbal medicine of Traditional Chinese Medicine, on sleep
disturbances in women withmenopause. METHODS: Totally 162 participants were
recruited for the treatment of sleep difficulty from February,2012 to December,
2014. Decoction of 200 mL was taken by every participant twice daily in half
anhour after lunch and dinner during two weeks. Sleep quality was assessed by
Pittsburg sleep quality index (PSQI) and menopausal symptoms and quality of life
were evaluated by the menopauserating scale (MRS) and the Chinese version of
World Health Organization quality of life-BREF at the finalfellow-up in the
fourth weekend after beginning. RESULTS: The average scores of PSQI had reduced
from (13.82 +/- 4.97) to (8.14 +/- 3.19), 95% CI(- 4.87, - 3.05) after 2-week
GGLMT treatment in the fourth week. GGLMT improved symptoms in patientswith more
severe conditions (MRS >= 16). Three adverse drug reaction, mouth ulcer,
constipation,and folliculitis, might be related with GGLMT and disappeared after
withdrawals of the treatment. CONCLUSION: For menopausal women suffering from
chronic sleep disturbances, our findings suggestthat two weeks treatment of GGLMT
was safe and effective.
PMID- 29956899
TI - Effects of Yishengukang decoction on expression of bone-specific alkaline
phosphatase, carboxyterminal propeptide of type I procollagen,and carboxyterminal
cross-linked telepeptide of type I collagen in malignant tumor patients with bone
metastasis.
AB - OBJECTIVE: To investigate the effect of Yishengukang decoction on the expression
of the metabolic bone markers, bone-specific alkaline phosphatase (BAP),
carboxyterminal propeptide of type I procollagen (PICP), and arboxyterminal cross
linked telepeptide of type I collagen (ICTP), in cancer patients with bone
metastasis. METHODS: Patients (n = 180) were divided into three groups: (a) bone
metastasis patients treatedwith Yishengukang and pamidronate disodium injection
(treatment group, n = 60); (b) bone metastasispatients treated with pamidronate
disodium injection alone (control group, n = 60); (c) cancer patientswithout
metastatic bone lesion (non-bone metastasis group, n = 60). Serum levels of the
metabolicmarkers BAP, PICP, and ICTP were detected by enzyme-linked immunosorbent
assay pre- and post-therapy. RESULTS: A significant decrease in serum BAP level
was observed in the treatment group comparedwith the control group. However there
were no significant differences in serum levels of PICP and ICTPbefore or after
treatment compared with the control group. CONCLUSION: Yishengukang decoction
combined with pamidronate disodium injection reduced serumBAP level to a greater
extent that pamidronate disodium injection alone. Furthermore, the
combinedtherapy was more beneficial in regulating imbalanced bone metabolism
after bone metastasis,and may represent the molecular mechanism underpinning the
effects of Yishengukang decoction.
PMID- 29956900
TI - Evaluation of Antinociceptive and Anti-inflammatory Activity of Phytosterol
Present in Chloroform Extract of Phyllanthus Maderaspatensis.
AB - Inflammation and pain is a common cause of medical consultation which generally
occurs when a tissue isinjured. In recent scenario, attention has been paid for
screening new drugs with analgesic activity from plantsources, to reduce or treat
pain with less adverse effects than allopathic drugs. The objectives of
thisresearch work was to evaluate the antinociceptive and anti-inflammatory
activity of phytosterol present inchloroform extract of Phyllanthus
maderaspatensis (CEPM) through carrageenan-induced hind paw oedemaand hot plate
method in male wistar rats. The test groups received CEPM (suspended in
1%caboxymethylcellulose, CMC) at doses 400 mg/kg, p.o.; the reference group
received indomethacin (10 mg/kg, in 1% CMC, p.o.) as positive control and the
negative control animals received the vehicle only (1%CMC, 10 mL/kg, p.o.). Oral
administration of CEPM or indomethacin showed significant (P<0.001) effect inthe
reduction of the paw oedema induced by 0.1 mL of 1% carrageenan (in 1% CMC)
solution into the subplantarregion. CEPM showed the highest inhibition 71.42% at
3rd hr. CEPM extract and pentazocinsignificantly (P<0.001) increases the basal
reaction time when compare to control group. The present studydemonstrates the
potential anti-inflammatory and analgesic effect of the CEPM which supports the
claims by the traditional medicine practitioners.
PMID- 29956901
TI - Effects of Shengjiangxiexin decoction on irinotecan-induced toxicity in patients
with UGT1A1*28 and UGT1A1*6 polymorphisms.
AB - OBJECTIVE: To evaluate the efficacy of Shengjiangxiexin decoction (SXD), prepared
with a formulafrom Traditional Chinese Medicine (TCM), in reducing irinotecan
induced hematological and gastrointestinaltoxicities in patients with UDP
glucuronosyltransferase (UGT)1A1*28 and UGT1A1*6 polymorphisms. METHODS: This
clinical trial included 115 patients receiving irinotecan combined with 5
fluorouracilplus l-leucovorin (FOLFIRI) treatment. All patients consented to
UGT1A1*28 and *6 gene polymorphismdetection prior to chemotherapy. SXD were
administered from 1 day prior to chemotherapy to6 day post chemotherapy.
Chemotherapy induced adverse reactions (neutropenia, diarrhea, nausea,vomiting,
anorexia and infection) were recorded, and short-term effect of chemotherapy was
evaluated regularly. RESULTS: A total of 50 patients had *1/*1 wild genotype, 58
patients had single allele variants withgenotype *1/*6 or *1/*28 , and 7 patients
had two alleles variants with genotype *6/*6, *28/*28 or *6/* 28. In *1/*6 or
*1/*28 patients (high risk group), 9 patients (15.5% ) developed I-II grade
diarrheaand no patient developed severe diarrhea; neutropenia occurred in 19
patients (32.8%) and only 3 patients(8.6% ) developed sever neutropenia. There
were no significant differences in any toxic effects(neutropenia, diarrhea,
nausea, vomiting, anorexia or infection) between *6 or *28 variant patients(high
risk group) and wild type patients. No sever toxicity was found in high risk two
alleles variantspatients (*6/*6, *6/*28 or *28/*28). No significant differences
were observed between UGT1A1*6/*28polymorphisms and clinical response of
chemotherapy. CONCLUSION: SXD could significantly reduce irinotecan-induced
hematological and gastrointestinaltoxicities in UGT1A1*28 or *6 variant patients
(high risk group), while this treatment didn't affect clinicalresponse of
chemotherapy.
PMID- 29956902
TI - Perceptions of Medical Teachers on the Faculty Development Programme.
AB - Background: Medical Council of India (MCI) insists on the training of Medical
Teachers in Medical Education Technologies (MET). The need for such a training is
debated by many teachers. Hence this study is taken up to analyse its benefits.
Subjects and Methods: Seven batches of medical teachers from a private Medical
College Hospital underwent a three day training in the basics of MET, as per the
guidelines of MCI. Pretest and post test for evaluation and feedback on
usefullness were obtained from the participants. Results & Discussion: The
results analysed with the statistical Graphpad Prism6 software showed
asignificantly high post test marks 7.09/10+/-1.395 (mean+/-SD) compared to the
pretest marks 2.184/10+/-1.019. (P value < 0.0001). Feedback in the Likertscale
format from more than 95% of the participants also pronounced the usefulness of
the programme. Conclusion: The statistically significant post test marks and the
Feedback (Likertscale) from the participants vouch for the necessity of the
training.
PMID- 29956903
TI - Effect of electro-acupuncture combined with psychological intervention on mental
symptoms and P50 of auditory evoked potentialin patients with internet addiction
disorder.
AB - OBJECTIVE: To observe the therapeutic effects of electro-acupuncture (EA)
combined with psychologicalintervention on the symptom of somzatization or
obsession and mental symptom of depressionor anxiety and P50 of Auditory Evoked
Potential (AEP) on internet addiction disorder (IAD). METHODS: One hundred and
twenty cases of IAD ere randomly divided into an EA group, a psycho-intervention
(PI) group and a comprehensive therapy (EA plus PI) group. Patients in the EA
groupwere treated with EA. Patients in the PI group were treated with cognition
and behavior therapy. Patientsin the EA plus PI group were treated with electro
acupuncture plus psychological intervention.Scores of IAD, scores of the symptom
checklist 90 (SCL-90), latency and amplitude of P50 of AEPwere measured before
and after treatment. RESULTS: The scores of IAD after treatment significantly
decreased in all groups (P < 0.05), and the scores of IAD in the EA plus PI group
were significantly lower than those in the other two groups (P < 0.05). The
scores of SCL-90 assembled and each factor after treatment in the EA plus PI
group significantly decreased (P < 0.05). After treatment in the EA plus PI
group, the amplitude distance of S1P50and S2P50 (S1-S2) significantly increased
(P < 0.05). CONCLUSION: EA combined with PI could relieve the mental symptoms of
IAD patients, and themechanism is possibly related to the increase of cerebrum
sense perception gating function.
PMID- 29956904
TI - Acute Effect of Electromagnetic Waves Emitted from Mobile Phone on Visual Evoked
Potential in Adult Male : A Preliminary Study.
AB - Electromagnetic waves (EMW) emitted from mobile phone (MP) may cause variety of
ocular effects, e.g.,cataract, corneal edema and lacrimation of eyes. Currently
very little information is available on acute effectsof EMW emitted from MP on
human visual system. So, study was planned to see the effects of EMWemitted from
MP on visual evoked potential (VEP). This study was conducted in 9 healthy male
subjectsin the age group of 20 40 years with history of exposure to MP for around
1 hour/day for the last 3-9 years.After explaining the whole procedure to the
subject, written consent was taken. Recording was done on RMSEMG EP MK-2 machine,
using 10/20 system of electrode placement. The electrodes were placed at
Cz(active electrode), O1-O2 (reference electrodes) and Fz (ground electrode). In
dark room, subject was madeto sit 1 meter away from screen of TV (275/350 mm
size). The black and white checks of 16/16 mm size(subtending an angle of 32
minutes of an arc) were generated on the monitor by an electronic
patterngenerator. The contrast between black and white checks was 67%. The checks
were made to reverse at arate of 1 Hz and 100 responses were recorded. The
subject was instructed to fix on small dot at its centerwith one eye; and the
other eye was closed with hand. Waves of VEP were recorded before and
afterexposure to MP kept near to right ear (as right ear was found to be dominant
ear, used by subjects to hearthe MP, so right eye was near to MP and had more
exposure compare to left eye) for 10 min. Statisticalanalysis was done by student
't' test. After exposure to MP in left eye, there was significant
increase(P<0.001) in latency of P100 wave without affecting the latency of other
waves. Although amplitude of P100-N 75 waves was reduced but not statistically
significant. But in right eye, after exposure to MP, latency ofN75 (P<0.001),
P100 (P<0.05) and N145 (P<0.001) waves were increased without any alteration in
amplitude ofP100 - P75 waves. Effect on right eye was slightly different. This
study suggests that EMW emitted from MP may affect the VEP.
PMID- 29956905
TI - Guasha improves the rating of perceived exertion scale score and reduces heart
rate variability in male weightlifters: a randomized controlledtrial.
AB - OBJECTIVE: To evaluate the effects of Guasha therapy on the rating of perceived
exertion (RPE) scalescore, and heart rate variability (HRV). METHODS: A
randomized controlled trial of Guasha (skin scraping) was compared with a
shamscraping group and control group. Sixteen sessions within an 8-week period
were completed. Sixty-fivemale weightlifters who had undergone normal
weightlifting training for a mean of 5 years beforestudy commencement were
recruited. The RPE scale score of "snatch", "clean and jerk" maneuvers(85% of one
repetition maximum), and HRV were measured before and after the intervention.
RESULTS: The RPE scale score for snatch, clean and jerk were reduced
significantly after intervention inthe Guasha group and sham group. However,
there was a significant difference in the low frequency(LF) domain and LF/high
frequency (HF) ratio (P < 0.05): the LF domain decreased, and the LF/HF ratio
decreased. CONCLUSION: Guasha could be used to reduce the RPE scale score, and
increase the response to HRV.Guasha could be considered as an alternative to some
types of recovery from sports training.
PMID- 29956906
TI - Protective effect of essential oil of Pistacia atlantica Desf. on peptic ulcer:
role of alpha-pinene.
AB - OBJECTIVE: To evaluate the efficacy of Pistacia atlantica Desf. oleoresin
essential oil on peptic ulcer(PU) and its antibacterial effect on metronidazole
resistant Helicobacter pylori, as well as chemical composition of the essential
oil. METHODS: The essential oil was standardized using gas chromatography mass
spectrometry (GC/MS) analysis. Acute toxicity of the essential oil was assessed
in animal model. In vitro anti-Helicobacterpylori activity was performed through
disc diffusion and minimum inhibitory concentration method.For gastroprotective
assay, rats received Pistacia atlantica Desf. essential oil (25, 50 and 100 mg/kg
orally) 1 h before induction of ulcer by ethanol. Macroscopic (ulcer index and
protection rate) andmicroscopic examination were performed. RESULTS: The GC/MS
analysis of the essential oil led to the identification of twenty constituents
andalpha-pinene is predominant constituent. The essential oil was safe up to 2000
mg/kg. All Helicobacter pyloristrains were susceptible to the essential oil and
the MIC ranged from 275 to 1100 MUg/mL. The ulcerindex for treated groups was
significantly reduced compared to control (P < 0.001) with EC(50) value of12.32
mg/kg. In microscopic examination, Pistacia atlantica attenuated destruction and
necrosis of gastric tissue. CONCLUSION: Current study exhibited protective effect
of standardized Pistacia atlantica essential oilagainst ethanol-induced gastric
ulcer and its antibacterial activity on Helicobacter pylori. alpha-pinenemight be
the responsible agent.
PMID- 29956907
TI - Electrochemically Controlled Solid Electrolyte Interphase Layers Enable Superior
Li-S Batteries.
AB - Lithium-sulfur (Li-S) batteries suffer from shuttle reactions during
electrochemical cycling, which cause the loss of active material sulfur from
sulfur-carbon cathodes, and simultaneously incur the corrosion and degradation of
the lithium metal anode by forming passivation layers on its surface. These
unwanted reactions therefore lead to the fast failure of batteries. The
preservation of the highly reactive lithium metal anode in sulfur-containing
electrolytes has been one of the main challenges for Li-S batteries. In this
study, we systematically controlled and optimized the formation of a smooth and
uniform solid electrolyte interphase (SEI) layer through electrochemical
pretreatment of the Li metal anode under controlled current densities. A distinct
improvement of battery performance in terms of specific capacity and power
capability was achieved in charge-discharge cycling for Li-S cells with
pretreated Li anodes compared to pristine untreated ones. Importantly, at a
higher power density (1 C rate, 3 mA cm-2), the Li-S cells with pretreated Li
anodes protected by a controlled elastomer (Li-Protected-by-Elastomer, LPE)) show
the suppression of the Li dendrite growth and exhibit 3-4 times higher specific
capacity than the untreated ones after 100 electrochemical cycles. The formation
of such a controlled uniform SEI was confirmed, and its surface chemistry,
morphology, and electrochemical properties were characterized by X-ray
photoelectron spectroscopy, focused-ion beam cross sectioning, and scanning
electron microscopy. Adequate pretreatment current density and time are critical
in order to form a continuous and uniform SEI, along with good Li-ion transport
property.
PMID- 29956908
TI - Tuning of the Topochemical Polymerization of Diacetylenes Based on an Odd/Even
Effect of the Peripheral Alkyl Chain: Thermochromic Reversibility in a Thin Film
and a Single-Component Ink for a Fountain Pen.
AB - The topochemical polymerization of diacetylenes (DAs) is closely related to the
length of their alkyl chain. DA monomers have two types of alkyl chain side
groups: the inner alkyl chain and the outer alkyl chain, that is, the peripheral
alkyl chain. Herein, we designed and synthesized a series of DA monomers that
possess bis-amide linkages with different peripheral alkyl chains ( n = 6-9; DA1
DA4). The peripheral alkyl chain length of these DA monomers exhibits an odd/even
effect on topochemical polymerization. The polymerization of DAs was achieved
only when n is an odd number, whereas no polymerization occurred when n is an
even number. The odd/even effect on the topochemical polymerization was also
investigated using ab initio density functional theory calculations. The
thermochromic reversibility of polydiacetylenes (PDAs) was investigated using UV
vis absorption spectroscopy at temperatures ranging from 20 to 60 degrees C.
Monomer DA2 was used as a single-component ink solution in a fountain pen that
can be transformed into thermochromic letters on conventional paper. Furthermore,
a PDA-embedded polyethylene oxide film was included to monitor the thermochromic
reversibility and was found to exhibit excellent thermochromic reversibility
between 20 and 100 degrees C and stability, enabling storage for a few months
without deformation. Finally, a green-colored patterned polymer film is readily
obtained by a subtractive color (blue and yellow) mixing method and exhibits high
thermochromic reversibility at temperatures between 20 and 100 degrees C.
PMID- 29956909
TI - Effects of Stiff Film Pattern Geometry on Surface Buckling Instabilities of
Elastic Bilayers.
AB - Buckling instabilities-such as wrinkling and creasing-of micropatterned elastic
surfaces play important roles in applications, including flexible electronics and
microfluidics. In many cases, the spatial dimensions associated with the imposed
pattern can compete with the natural length scale of the surface instabilities
(e.g., the wrinkle wavelength), leading to a rich array of surface buckling
behaviors. In this paper, we consider elastic bilayers consisting of a spatially
patterned stiff film supported on a continuous and planar soft substrate. Through
a combination of experimental and computational analyses, we find that three
surface instability modes-wrinkling, Euler buckling, and rigid rotation-are
observed for the stiff material patterns, depending on the in-plane dimensions of
the film compared to the natural wrinkle wavelength, while the intervening soft
regions undergo a creasing instability. The interplay between these instabilities
leads to a variety of surface structures as a function of the pattern geometry
and applied compressive strain, in many cases yielding contact between
neighboring stiff material elements because of the formation of creases in the
gaps between them.
PMID- 29956910
TI - Role of Surface Phenolic-OH Groups in N-Rich Porous Organic Polymers for
Enhancing the CO2 Uptake and CO2/N2 Selectivity: Experimental and Computational
Studies.
AB - Design and successful synthesis of phenolic-OH and amine-functionalized porous
organic polymers as adsorbent for postcombustion CO2 uptake from flue gas
mixtures along with high CO2/N2 selectivity is a very demanding research area in
the context of developing a suitable adsorbent to mitigate greenhouse gases.
Herein, we report three triazine-based porous organic polymers TrzPOP-1, -2, and
3 through the polycondensation of two triazine rings containing tetraamine and
three dialdehydes. These porous organic polymers possess high Brunauer-Emmett
Teller (BET) surface areas of 995, 868, and 772 m2 g-1, respectively. Out of the
three materials, TrzPOP-2 and TrzPOP-3 contain additional phenolic-OH groups
along with triazine moiety and secondary amine linkages. At 273 K, TrzPOP-1, -2,
and -3 displayed CO2 uptake capacities of 6.19, 7.51, and 8.54 mmol g-1,
respectively, up to 1 bar pressure, which are considerably high among all porous
polymers reported till date. Despite the lower BET surface area, TrzPOP-2 and
TrzPOP-3 containing phenolic-OH groups showed higher CO2 uptakes. To understand
the CO2 adsorption mechanism, we have further performed the quantum chemical
studies to analyze noncovalent interactions between CO2 molecules and different
polar functionalities present in these porous polymers. TrzPOP-1, -2, and -3 have
the capability of selective CO2 uptake over that of N2 at 273 K with the
selectivity of 61:1, 117:1, and 142:1 by using the initial slope comparing
method, along with 108.4, 140.6, and 167.4 by using ideal adsorbed solution
theory (IAST) method, respectively. On the other hand, at 298 K, the calculated
CO2/N2 selectivities in the initial slope comparing method for TrzPOP-1, -2, and
3 are 27:1, 72:1, and 96:1, whereas those using IAST method are 42.1, 75.7, and
94.5, respectively. Cost effective and scalable synthesis of these porous
polymeric materials reported herein for selective CO2 capture has a very
promising future for environmental clean-up.
PMID- 29956911
TI - Doping-Free Complementary Logic Gates Enabled by Two-Dimensional Polarity
Controllable Transistors.
AB - Atomically thin two-dimensional (2D) materials belonging to transition metal
dichalcogenides, due to their physical and electrical properties, are an
exceptional vector for the exploration of next-generation semiconductor devices.
Among them, due to the possibility of ambipolar conduction, tungsten diselenide
(WSe2) provides a platform for the efficient implementation of polarity
controllable transistors. These transistors use an additional gate, named
polarity gate, that, due to the electrostatic doping of the Schottky junctions,
provides a device-level dynamic control of their polarity, that is, n- or p-type.
Here, we experimentally demonstrate a complete doping-free standard cell library
realized on WSe2 without the use of either chemical or physical doping. We show a
functionally complete family of complementary logic gates (INV, NAND, NOR, 2
input XOR, 3-input XOR, and MAJ) and, due to the reconfigurable capabilities of
the single devices, achieve the realization of highly expressive logic gates,
such as exclusive-OR (XOR) and majority (MAJ), with fewer transistors than
possible in conventional complementary metal-oxide-semiconductor logic. Our work
shows a path to enable doping-free low-power electronics on 2D semiconductors,
going beyond the concept of unipolar physically doped devices, while suggesting a
road to achieve higher computational densities in two-dimensional electronics.
PMID- 29956912
TI - Graphene Oxide-Assisted Accumulation and Layer-by-Layer Assembly of Antibacterial
Peptide for Sustained Release Applications.
AB - Fabrication of antibacterial materials with sustained release of active
components is of great importance for long-term antibacterial applications.
Graphene oxide (GO) has been found to be an excellent carrier for accumulating
the antibacterial peptide of G(IIKK)4I-NH2 and mediating its loading into the
layer-by-layer (LBL) films for sustained release applications. G(IIKK)4I-NH2
takes random coiled conformation in monomeric state below 0.17 mM but self
assembles into supramolecular aggregates with alpha-helical secondary structure
at higher concentrations. It can bind onto GO surface in both monomeric and
aggregate states to form stable GO@G(IIKK)4I-NH2 composites. Upon binding, the
local amphiphilic environment of GO surface induces a conformational transition
of G(IIKK)4I-NH2 monomers from random coils to alpha-helix. The aggregate binding
enhances the loading amount greatly. GO (1 mg) can load as high as 1.7 mg of
peptide at saturation. This enables the GO@G(IIKK)4I-NH2 composites to serve as
reservoirs for sustained release of active G(IIKK)4I-NH2 monomers. Moreover,
G(IIKK)4I-NH2 itself shows low efficiency in LBL assembly, whereas the
GO@G(IIKK)4I-NH2 composites are ideal LBL assembling units with highly enhanced
loading efficiency of G(IIKK)4I-NH2. The LBL films involving degradable poly(beta
amino esters) can realize sustained release of G(IIKK)4I-NH2 for bacteria killing
in a well-controlled manner. This study demonstrates an efficient strategy for
fabrication of long-durable antibacterial materials and surface coatings by using
GO as the carrier for drug accumulation and loading.
PMID- 29956914
TI - Native Mass Spectrometry, Ion Mobility, and Collision-Induced Unfolding for
Conformational Characterization of IgG4 Monoclonal Antibodies.
AB - Although the majority of FDA and EMA approved therapeutic monoclonal antibodies
(mAbs) are IgG1, the number of IgG4-based formats reaching the market is
increasing. IgG4 differs from other mAb isotypes by its specificity to form half
mAbs that recombine into bispecific (bsAbs) molecules, through a process termed
fab-arm exchange (FAE). We report here the complementarity of native mass
spectrometry (MS), ion mobility (IM), and collision-induced unfolding (CIU)
experiments for the structural characterization of members of the IgG4 subfamily
(wild-type (wt), hinge-stabilized (hs, S228P mutation), and the resulting bsAb
IgG4s). Native MS allows confirming/invalidating the occurrence of FAE as a
function of these different types of IgG4. While IM-MS was unable to distinguish
iso-cross-section IgG4 species, CIU experiments provide unique specific
structural signatures of each individual IgG4 based on their specific unfolding
pathways. Common CIU features of IgG4 formats include the observation of three
conformational states and two transitions. In addition, CIU experiments
demonstrated that S228P mutation stabilizes gas phase conformations of hsIgG4, in
agreement with increased stability related to more rigid hinge regions. CIU
patterns also appear to be more informative than IM-MS for bsAb structural
characterization, unfolding signature of the bsAb being intermediate to the ones
of the former parent wt-IgG4s, highlighting that bsAb CIU profiles keep the
memory of their origins. Altogether, our results demonstrate that CIU patterns
can serve as mAb specific structural signatures and are mature to be included in
MS-based analytical workflows for conformational/structural characterization of
mAb formats in early development phases and for multiple attribute monitoring.
PMID- 29956913
TI - High-Performance Cable-Type Flexible Rechargeable Zn Battery Based on MnO2@CNT
Fiber Microelectrode.
AB - Nowadays, linear-shaped batteries have received increasing attentions because the
unique one-dimensional architecture offers an omni-directional flexibility. We
developed a cable-type flexible rechargeable Zn microbattery based on a
microscale MnO2@carbon nanotube fiberlike composite cathode and Zn wire anode.
The Zn-MnO2 cable microbattery exhibits a large specific capacity, good rate
performance, and cyclic stability. The capacity of Zn-MnO2 cable batteries are
322 and 290 mAh/g based on MnO2 with aqueous and gel polymer electrolyte,
corresponding to the specific energy of 437 and 360 Wh/kg, respectively. Besides,
the Zn-MnO2 cable battery shows excellent flexibility, which can be folded into
arbitrary shapes without sacrificing electrochemical performance. Furthermore, we
studied electrochemical properties of Zn-MnO2 cable microbatteries with different
Zn salt electrolytes, such as Zn salt with small anions (ZnSO4 or ZnCl2, etc.)
and Zn salt with bulky anions (Zn(CF3SO3)2, etc.). With the merits of impressive
electrochemical performance and flexibility, this first flexible rechargeable Zn
MnO2 cable-like battery presents a new approach to develop high-performance power
sources for portable and wearable electronics.
PMID- 29956915
TI - Correction to Nanocrystalline Titanium Metal-Organic Frameworks for Highly
Efficient and Flexible Perovskite Solar Cells.
PMID- 29956916
TI - 1064 nm Dispersive Raman Microspectroscopy and Optical Trapping of Pharmaceutical
Aerosols.
AB - Raman spectroscopy is a powerful tool for investigating chemical composition.
Coupling Raman spectroscopy with optical microscopy (Raman microspectroscopy) and
optical trapping (Raman tweezers) allows microscopic length scales and, hence,
femtolitre volumes to be probed. Raman microspectroscopy typically uses
UV/visible excitation lasers, but many samples, including organic molecules and
complex tissue samples, fluoresce strongly at these wavelengths. Here we report
the development and application of dispersive Raman microspectroscopy designed
around a near-infrared continuous wave 1064 nm excitation light source. We
analyze microparticles (1-5 MUm diameter) composed of polystyrene latex and from
three real-world pressurized metered dose inhalers (pMDIs) used in the treatment
of asthma: salmeterol xinafoate (Serevent), salbutamol sulfate (Salamol), and
ciclesonide (Alvesco). For the first time, single particles are captured,
optically levitated, and analyzed using the same 1064 nm laser, which permits a
convenient nondestructive chemical analysis of the true aerosol phase. We show
that particles exhibiting overwhelming fluorescence using a visible laser (514.5
nm) can be successfully analyzed with 1064 nm excitation, irrespective of sample
composition and irradiation time. Spectra are acquired rapidly (1-5 min) with a
wavelength resolution of 2 nm over a wide wavenumber range (500-3100 cm-1). This
is despite the microscopic sample size and low Raman scattering efficiency at
1064 nm. Spectra of individual pMDI particles compare well to bulk samples, and
the Serevent pMDI delivers the thermodynamically preferred crystal form of
salmeterol xinafoate. 1064 nm dispersive Raman microspectroscopy is a promising
technique that could see diverse applications for samples where fluorescence-free
characterization is required with high spatial resolution.
PMID- 29956917
TI - DARK Classics in Chemical Neuroscience: Psilocybin.
AB - Psilocybin is found in a family of mushrooms commonly known as "magic mushrooms"
that have been used throughout history to induce hallucinations. In the late
1950s Albert Hofmann, of Sandoz Laboratories, identified and synthesized the
psychoactive compounds psilocybin and psilocin which are found in psilocybe
mushrooms. Psilocybin was marketed by Sandoz as Indocybin for basic
psychopharmacological and therapeutic clinical research. Psilocybin saw a rapid
rise in popularity during the 1960s and was classed as a Schedule I drug in 1970.
This led to a significant decrease in psilocybin research. Recently, however,
preliminary studies with psilocybin have shown promise as potential for the
treatment of obsessive compulsive disorder, alcohol addiction, tobacco addiction,
and major depressive disorder, and the treatment of depression in terminally ill
cancer patients. This review describes in detail the synthesis, metabolism,
pharmacology, adverse drug reactions, and importance of psilocybin to
neuroscience in the past and present.
PMID- 29956918
TI - All-in-One Compact Architecture toward Wearable All-Solid-State, High-Volumetric
Energy-Density Supercapacitors.
AB - High-performance flexible energy storage devices are an important prerequisite to
the utilization of various advanced wearable electronics, such as healthcare
sensors and smart textiles. In this work, we design a wearable all-solid-state,
all-in-one asymmetric supercapacitor by integrating current collectors, a
separator, and negative and positive electrodes into a thin, flexible, and porous
polyamide nanofiber film. The positive and negative electrodes are, respectively,
electrodeposited onto each side of the carbon nanotube-modified porous polyamide
nanofiber film to form the integrated and compact asymmetric cell. The all-in-one
thin-film asymmetric supercapacitor is binder-, additive-, and metal current
collector-free, which can effectively decrease the cost, simplify the assembly
procedures, and increase the energy density. The assembled flexible all-in-one
asymmetric supercapacitor with a compact structure shows high gravimetric and
volumetric specific capacitances of 70 F g-1 and 3.1 F cm-3 under a current
density of 0.5 A g-1 in a neutral polyvinyl alcohol/LiCl gel electrolyte,
respectively. Additionally, the all-in-one asymmetric cell displays a favorable
volumetric energy density of 1.1 W h L-3, which is among the highest compared
with other reported flexible solid-state supercapacitors. Notably, multiple cell
units can be integrated in one piece of polyamide nanofiber film and connected in
series to satisfy the need of high output voltage.
PMID- 29956919
TI - UV-Raman Spectroscopic Identification of Fungal Spores Important for Respiratory
Diseases.
AB - Fungal spores are one of several environmental factors responsible for causing
respiratory diseases like asthma, chronic obstructive pulmonary disease (COPD),
and aspergillosis. These spores also are able to trigger exacerbations during
chronic forms of disease. Different fungal spores may contain different allergens
and mycotoxins, therefore the health hazards are varying between the species.
Thus, it is highly important quickly to identify the composition of fungal spores
in the air. In this study, UV-Raman spectroscopy with an excitation wavelength of
244 nm was applied to investigate eight different fungal species implicated in
respiratory diseases worldwide. Here, we demonstrate that darkly colored spores
can be directly examined, and UV-Raman spectroscopy provides the information
sufficient for classifying fungal spores. Classification models on the genus,
species, and strain levels were built using a combination of principal component
analysis and linear discriminant analysis followed by evaluation with leave-one
batch-out-cross-validation. At the genus level an accuracy of 97.5% was achieved,
whereas on the species level four different Aspergillus species were classified
with 100% accuracy. Finally, classifying three strains of Aspergillus fumigatus
an accuracy of 89.4% was reached. These results demonstrate that UV-Raman
spectroscopy in combination with innovative chemometrics allows for fast
identification of fungal spores and can be a potential alternative to currently
used time-consuming cultivation.
PMID- 29956920
TI - Size-Dependent Physical and Electrochemical Properties of Two-Dimensional MXene
Flakes.
AB - Two-dimensional (2D) particles, including transition metal carbides (MXenes),
often exhibit large lateral-size polydispersity in delaminated colloidal
solutions. This heterogeneity results in challenges when conducting fundamental
studies, such as investigating correlations between properties and the 2D flake
size. To resolve this challenge, we have developed solution-processable
techniques to control and sort 2D titanium carbide (Ti3C2T x) MXene flakes after
synthesis based on sonication and density gradient centrifugation, respectively.
By tuning the sonication conditions, Ti3C2T x flakes with varied lateral sizes,
ranging from 0.1 to ~5 MUm, can be obtained. Furthermore, density gradient
centrifugation was used to sort Ti3C2T x flakes with different lateral sizes into
more monodisperse fractions. These processing techniques allow for the
characterization of size-dependent optical and electronic properties by measuring
the absorption spectra and film conductivity, respectively. Additionally, by
testing the material as electrochemical capacitor electrodes, we show the Ti3C2T
x flake-size dependence of electrochemical performance. Ti3C2T x films made of
flakes with lateral sizes of ~1 MUm showed the best capacitance of 290 F/g at 2
mV/s and rate performance with 200 F/g at 1000 mV/s. The work provides a general
methodology which can be followed to control the size of MXenes and other 2D
materials for a variety of applications and fundamental size-dependent studies.
PMID- 29956921
TI - Double Dehydrogenation of Primary Amines to Nitriles by a Ruthenium Complex
Featuring Pyrazole Functionality.
AB - A ruthenium(II) complex bearing a naphthyridine-functionalized pyrazole ligand
catalyzes oxidant-free and acceptorless selective double dehydrogenation of
primary amines to nitriles at moderate temperature. The role of the proton
responsive entity on the ligand scaffold is demonstrated by control experiments,
including the use of a N-methylated pyrazole analogue. DFT calculations reveal
intricate hydride and proton transfers to achieve the overall elimination of 2
equiv of H2.
PMID- 29956922
TI - X-ray-Induced Photoreduction of Hg(II) in Aqueous Frozen Solution Yields Nearly
Monatomic Hg(0).
AB - We use X-ray-induced photochemistry, which is well known to cause changes in a
number of systems, to reduce Hg(II) to Hg(0) in frozen aqueous solution with
added glycerol maintained at 10 K. X-ray absorption spectroscopy was used to
monitor the extent of the reaction and to characterize the species. An analysis
of the extended X-ray absorption fine structure (EXAFS) of the photochemical
product indicated a nearly monatomic Hg(0) species bound only by long, weak bonds
to oxygens at ~3.5 A. The results of the EXAFS analysis agree quantitatively with
the results of density functional theory calculations using the meta-GGA
approximation with the M11-L functional. This is the first structural
characterization of nearly monatomic Hg(0) bound by hard ligands similar to those
expected in aqueous environmental systems. We conclude that Hg(0) is expected to
exist in solution as a nearly monatomic entity.
PMID- 29956923
TI - A Yeast Three Hybrid Assay for Metabolic Engineering of Tetracycline Derivatives.
AB - Metabolic engineering stands to transform the discovery and production of a wide
range of chemicals, but metabolic engineering currently demands considerable
resource investments that restrict commercial application. To facilitate the
applicability of metabolic engineering, general high-throughput and readily
implemented technologies are needed to assay vast libraries of strains producing
desirable chemicals. Toward this end, we describe here the development of a yeast
three hybrid (Y3H) assay as a general, high-throughput, versatile and readily
implemented approach for the detection of target molecule biosynthesis. Our
system detects target molecule biosynthesis through a change in reporter gene
transcription that results from the binding of the target molecule to a modular
protein receptor. We demonstrate the use of the Y3H assay for detecting the
biosynthesis of tetracyclines, a major class of antibiotics, based on the
interaction between tetracyclines and the tetracycline repressor protein (TetR).
Various tetracycline derivatives can be detected using our assay, whose
versatility enables its use both as a screen and a selection to match the needs
and instrumentation of a wide range of end users. We demonstrate the
applicability of the Y3H assay to metabolic engineering by differentiating
between producer and nonproducer strains of the natural product tetracycline TAN
1612. The Y3H assay is superior to state-of-the-art HPLC-MS methods in throughput
and limit of detection of tetracycline derivatives. Finally, our establishment of
the Y3H assay for detecting the biosynthesis of a tetracycline supports the
generality of the Y3H assay for detecting the biosynthesis of many other target
molecules.
PMID- 29956924
TI - On-Surface Reactions in the Growth of High-Quality CdSe Nanocrystals in Nonpolar
Solutions.
AB - On-surface reaction mechanisms during the growth of high-quality CdSe
nanocrystals are studied quantitatively and systematically by introducing a
cyclic growth scheme. Prior to the repeating growth cycles, presynthesized CdSe
QD seeds from a conventional scheme are reacted with an activated Se precursor,
which is found to include three elementary steps and generate Se-terminated CdSe
QDs. The cyclic growth in amine-octadecene solution includes two repeating half
reactions. The first half-reaction is between cadmium carboxylates in the bulk
solution and the Se-terminated QDs, and the other is between the Se precursor in
the bulk solution and the Cd-terminated QDs generated by the first half-reaction.
While two elementary steps in the Se-surface half-reaction can be quantitatively
treated as parallel kinetics, two elementary steps for the Cd-surface half
reaction must be treated as consecutive steps. These elementary steps are found
to possess substantially different reaction rates as well as activation energies.
Results indicate that, in the growth of compound semiconductor nanocrystals with
metal carboxylates as cationic precursor (or ligands), the elementary step
between activated anionic precursors in the bulk solution and the cationic sites
on the surface of nanocrystals would be the rate-limiting step. This rate
limiting step should be the one that causes nucleation (or formation of small
clusters by solution reactions) to be substantially faster than the corresponding
growth through on-surface reactions.
PMID- 29956925
TI - Elucidating Allosteric Communications in Proteins with Difference Contact Network
Analysis.
AB - A difference contact network analysis (dCNA) method is developed for delineating
allosteric mechanisms in proteins. The new method addresses limitations of
conventional network analysis methods and is particularly suitable for allosteric
systems undergoing large-amplitude conformational changes during function. Tests
show that dCNA works well for proteins of varying sizes and functions. The design
of dCNA is general enough to facilitate analyses of diverse dynamic data
generated by molecular dynamics, crystallography, or nuclear magnetic resonance.
PMID- 29956926
TI - Defect Engineering for High-Performance n-Type PbSe Thermoelectrics.
AB - Introducing structural defects such as vacancies, nanoprecipitates, and
dislocations is a proven means of reducing lattice thermal conductivity. However,
these defects tend to be detrimental to carrier mobility. Consequently, the
overall effects for enhancing ZT are often compromised. Indeed, developing
strategies allowing for strong phonon scattering and high carrier mobility at the
same time is a prime task in thermoelectrics. Here we present a high-performance
thermoelectric system of Pb0.95(Sb0.033?0.017)Se1- yTe y (? = vacancy; y = 0-0.4)
embedded with unique defect architecture. Given the mean free paths of phonons
and electrons, we rationally integrate multiple defects that involve point
defects, vacancy-driven dense dislocations, and Te-induced nanoprecipitates with
different sizes and mass fluctuations. They collectively scatter thermal phonons
in a wide range of frequencies to give lattice thermal conductivity of ~0.4 W m-1
K-1, which approaches to the amorphous limit. Remarkably, Te alloying increases a
density of nanoprecipitates that affect mobility negligibly and impede phonons
significantly, and it also decreases a density of dislocations that scatter both
electrons and phonons heavily. As y is increased to 0.4, electron mobility is
enhanced and lattice thermal conductivity is decreased simultaneously. As a
result, Pb0.95(Sb0.033?0.017)Se0.6Te0.4 exhibits the highest ZT ~ 1.5 at 823 K,
which is attributed to the markedly enhanced power factor and reduced lattice
thermal conductivity, in comparison with a ZT ~ 0.9 for Pb0.95(Sb0.033?0.017)Se
that contains heavy dislocations only. These results highlight the potential of
defect engineering to modulate electrical and thermal transport properties
independently. We also reveal the defect formation mechanisms for dislocations
and nanoprecipitates embedded in Pb0.95(Sb0.033?0.017)Se0.6Te0.4 by atomic
resolution spherical aberration-corrected scanning transmission electron
microscopy.
PMID- 29956927
TI - Conductive Leaflike Cobalt Metal-Organic Framework Nanoarray on Carbon Cloth as a
Flexible and Versatile Anode toward Both Electrocatalytic Glucose and Water
Oxidation.
AB - Transition metal-organic frameworks (MOFs), on account of their unique inherent
properties of large pore volume, high specific surface area, tunable pores, and
good catalytic activity, have been highly regarded as superior catalysts recently
for water electrolysis, supercapacitors, batteries, sensors, and so on. Herein,
we report on a cobalt MOF phase with 3D well-aligned nanosheets array
architecture on carbon cloth (Co-MOF NS/CC), fabricated by a facile ambient
liquid-phase deposition, could serve as a self-standing Janus catalytic electrode
toward both glucose and water oxidation. It shows good glucose-sensing
performance with low determination limit and large detection range. Also, it
exhibits high water-oxidation efficiency with low overpotential and good
durability. This work demonstrates the potential of utilizing transition-metal
based well-aligned MOF nanoarrays for electrocatalytic oxidation.
PMID- 29956928
TI - Small Molecule Driven Stabilization of Promoter G-Quadruplexes and
Transcriptional Regulation of c-MYC.
AB - G-quadruplexes have been considered attractive therapeutic targets for the
development of anticancer agents. We herein report synthesis of a series of
carbazole derivatives by employing modular one-pot Cu(I) catalyzed cycloaddition.
These carbazole derivatives are easily synthesizable, soluble in aqueous media,
and able to strongly interact with quadruplexes. FRET based melting assay and
fluorescence titration experiments suggest that a carbazole derivative, Cz-1,
preferentially binds c-MYC quadruplex DNA over other investigated quadruplex and
duplex DNAs. The biological studies revealed that Cz-1 inhibits cancer cell
proliferation by inducing apoptosis. Moreover, Cz-1 inhibits the expression of c
MYC at transcriptional as well as translational levels. Exon-specific-assay
confirms that the downregulation of MYC expression is mainly driven by the
binding of Cz-1 with the promoter G-quadruplex structures. Immunocytochemistry,
using quadruplex binding antibody BG4, further suggests that Cz-1 induces and
stabilizes G-quadruplexes in a cellular system.
PMID- 29956929
TI - Simplifying G Protein-Coupled Receptor Isolation with a Calcium-Dependent
Fragment Complementation Affinity System.
AB - The process of isolating recombinant G protein-coupled receptors from membrane
preparations is challenging because the process requires solubilization in
detergent micelles and multistep affinity chromatography protocols.
Solubilization buffers contain high concentrations of salts, detergents, and
glycerol that create stringent conditions necessary to stabilize the receptor but
in which affinity chromatography resins perform poorly, and these resins also
require the addition of eluting agents that complicate downstream assays. To
simplify this process we have developed a high affinity fragment complementation
molecular switch as a highly specific system for receptor capture in
solubilization buffer with a calcium chelation-based elution step releasing
functional protein in a simple buffer. Here we describe in detail the design,
methodology, interpretation, and limitations of this novel affinity
chromatography system in the isolation and purification of the cannabinoid G
protein-coupled receptor CB2, in comparison with commercially available systems.
This powerful tool may be applied to any recombinant membrane bound protein and
can be further optimized to enhance the yield and purity of the most challenging
protein targets for study.
PMID- 29956930
TI - Puzzle of the Intramolecular Hydrogen Bond of Dibenzoylmethane Resolved by
Molecular Dynamics Simulations.
AB - The enol form of dibenzoylmethane has been the subject of many experimental and
theoretical studies, yet the symmetry and the spectral response of the OHO
intramolecular hydrogen bond remains mysterious due to conflicting assignments.
In order to qualitatively understand the complex proton dynamics, it is necessary
to probe the neighborhood of stationary points on the potential energy landscape.
Here, we employ density functional theory-based molecular dynamics (DFT-MD)
simulations to sample the coupling between the intermolecular proton transfer and
all other molecular modes. To account for the quantum nature of the proton
motion, we employ the path integral formalism within the DFT-MD simulations. Our
results reveal that the hydrogen-bonded proton is delocalized between two oxygen
atoms with sightly higher probability to be observed in the asymmetric than the
symmetric position. The simulated infrared spectrum is found to be in a
reasonably good agreement with the experimental spectrum. The computed nuOH band
is remarkably broad and centered around 2640 cm-1. The origin of the discrepancy
between the simulated and experimental intensities of the nuOH band is discussed.
PMID- 29956931
TI - Co-Catalyzed Synthesis of N-Sulfonylcarboxamides from Carboxylic Acids and
Sulfonyl Azides.
AB - A Co-catalyzed effective synthesis of N-sulfonylcarboxamides from the reaction of
carboxylic acids and organic azides in the presence of isocyanide has been
developed. The protocol has the advantages of short time, low temperature, and
being oxidant-free, which provides a new and simple approach for the synthesis of
N-sulfonylcarboxamides in good to excellent yields with a broad substrate scope.
PMID- 29956933
TI - Asymmetric Construction of Bispiro[oxindole-pyrrolidine-rhodanine]s via
Squaramide-Catalyzed Domino Michael/Mannich [3 + 2] Cycloaddition of Rhodanine
Derivatives with N-(2,2,2-Trifluoroethyl)isatin Ketimines.
AB - Squaramide-catalyzed asymmetric domino Michael/Mannich [3 + 2] cycloaddition
reaction between rhodanine derivatives and N-(2,2,2-trifluoroethyl)isatin
ketimines has been developed to synthesize various bispiro[oxindole-pyrrolidine
rhodanine]s with good to excellent yields (up to 99%) and excellent
stereoselectivities (up to >99% ee and >99:1 dr). The biologically active
rhodanine, oxindole, and pyrrolidine moieties were embedded in these novel
bispirocyclic products, which will provide some support for the enrichment of
chiral heterocyclic compound databases with potential medical value.
PMID- 29956932
TI - CO Release from N,C,S-Pincer Iron(III) Carbonyl Complexes Induced by Visible-to
NIR Light Irradiation: Mechanistic Insight into Effects of Axial Phosphorus
Ligands.
AB - Light-induced CO release from newly synthesized N,C,S-pincer iron(III) carbonyl
complexes with two phosphorus ligands- trans-[Fe(L-kappa3 N,C,S)(CO)(PR2R')2]PF6
([1]PF6, R = Me, R' = Ph; [2]PF6, R = R' = Me; [3]PF6, R = R' = OEt)-were
investigated. All the iron(III) carbonyl complexes were stable in solution and
showed light-inducible CO release under ambient conditions. Studies on the
wavelength dependence of photoreaction revealed that the phosphite complex [3]PF6
exhibited the most extended photosensitivity including all visible and a part of
near-IR light (390-800 nm wavelengths). The phosphine complexes [1]PF6 and [2]PF6
showed sensitivity to only the higher-energy region of visible light (390-450
nm). Quantum-chemical calculations and spectroscopic data suggested that all
complexes [1]PF6-[3]PF6 have dpi-dpi excitation modes to depopulate Fe
C(carbonyl) bonding and potentially induce the CO release by irradiation of light
in the near-IR region, although moderately weakened Fe-C(carbonyl) bonding due to
stronger pi-backbonding by the phosphite ligand rendered the excitation effective
on the CO release exclusively in [3]PF6.
PMID- 29956934
TI - Guest-Induced Switchable Breathing Behavior in a Flexible Metal-Organic Framework
with Pronounced Negative Gas Pressure.
AB - Flexible metal-organic frameworks (MOFs) have attracted great interest for their
dynamically structural transformability in response to external stimuli. Herein,
we report a switchable "breathing" or "gate-opening" behavior associated with the
phase transformation between a narrow pore (np) and a large pore (lp) in a
flexible pillared-layered MOF, denoted as MOF-1 as, which is also confirmed by
SCXRD and PXRD. The desolvated phase (MOF-1 des) features a unique stepwise
adsorption isotherm for N2 coupled with a pronounced negative gas adsorption
pressure. For comparison, however, no appreciable CO2 adsorption and gate-opening
phenomenon with stepwise sorption can be observed. Furthermore, the polar
micropore walls decorated with thiophene groups in MOF-1 des reveals the
selective sorption of toluene over benzene and p-xylene associated with self
structural adjustment in spite of the markedly similar physicochemical properties
of these vapor molecules.
PMID- 29956936
TI - Nickel-Catalyzed Intramolecular Arylcyanation for the Synthesis of 3,3
Disubstituted Oxindoles.
AB - A nickel-catalyzed arylcyanation reaction for the synthesis of 3,3-disubstituted
oxindoles has been developed. This method features a bench-stable precatalyst
system and serves as an economical alternative to the existing palladium
catalyzed arylcyanations described to date. A wide scope of oxindole products
were accessible in moderate to good yields, and the rich chemistry of the newly
installed nitrile functional group was demonstrated in the synthesis of various
oxindole derivatives.
PMID- 29956935
TI - Multistates and Polyamorphism in Phase-Change K2Sb8Se13.
AB - The phase-change (PC) materials in the majority of optical data storage media in
use today exhibit a fast, reversible crystal -> amorphous phase transition that
allows them to be switched between on (1) and off (0) binary states. Solid-state
inorganic materials with this property are relatively common, but those
exhibiting an amorphous -> amorphous transition called polyamorphism are
exceptionally rare. K2Sb8Se13 (KSS) reported here is the first example of a
material that has both amorphous -> amorphous polyamorphic transition and
amorphous -> crystal transition at easily accessible temperatures (227 and 263
degrees C, respectively). The transitions are associated with the atomic
coordinative preferences of the atoms, and all three states of K2Sb8Se13 are
stable in air at 25 degrees C and 1 atm. All three states of K2Sb8Se13 exhibit
distinct optical bandgaps, Eg = 1.25, 1.0, and 0.74 eV, for the amorphous-II,
amorphous-I, and crystalline versions, respectively. The room-temperature
electrical conductivity increases by more than 2 orders of magnitude from
amorphous-I to -II and by another 2 orders of magnitude from amorphous-II to the
crystalline state. This extraordinary behavior suggests that a new class of
materials exist which could provide multistate level systems to enable higher
order computing logic circuits, reconfigurable logic devices, and optical
switches.
PMID- 29956937
TI - Synthesis of Vinyl Cyclopropanes via Anion Relay Cyclization.
AB - A method where an allyl alcohol is formed from a Tsuji-Trost allylation between a
vinyl epoxide and an acyl containing nucleophile is described. Subsequently, a
retro-Claisen condensation is utilized as a means of through-space anion relay.
The anion relay results in the formation of a reactive carbanion and
simultaneously activates an allylic alcohol toward intramolecular Tsuji-Trost
cyclopropanation. Hence, in one pot, Tsuji-Trost allylation, retro-Claisen
activation, and Tsuji-Trost cyclopropanation are combined to access synthetically
useful vinyl cyclopropanes from vinyl epoxides using a mild and operationally
simple procedure.
PMID- 29956938
TI - Correction to "Tryptic Peptides Bearing C-Terminal Dimethyllysine Need to Be
Considered during the Analysis of Lysine Dimethylation in Proteomic Study".
PMID- 29956939
TI - Synthesis of the Halichondrin C1-C15 Fragment from a Halaven C27-C35 Byproduct:
Stereospecific Intramolecular Kishi Reduction.
AB - A byproduct from a Halaven C27-C35 manufacturing process was transformed into a
crystalline halichondrin C1-C15 building block by employing a stereospecific
intramolecular Kishi reduction as the key step.
PMID- 29956940
TI - Merging Visible-Light Photocatalysis and Transition-Metal Catalysis in Three
Component Alkyl-Fluorination of Olefins with a Fluoride Ion.
AB - The light-induced, Ru-catalyzed three-component alkyl-fluorination of olefins
under mild reaction conditions is reported. This carbofluorination reaction
features a wide substrate scope and good functional group tolerance. A key
advantage of this photoredox reaction is the use of nucleophilic fluoride and
generic alkyl groups. Late-stage functionalizations are achieved, and a copper
assisted oxidative quenching mechanism is proposed based on the mechanistic
studies.
PMID- 29956941
TI - Copper-Catalyzed Silylation of C(sp3)-H Bonds Adjacent to Amide Nitrogen Atoms.
AB - A copper-catalyzed C-Si bond formation between N-halogenated amides and Si-B
reagents is described. This oxidative coupling enables the silylation of C(sp3)-H
bonds alpha to an amide nitrogen atom. The utility of the new method is
demonstrated for sulfonamides, and N-chlorination with tBuOCl and C-H silylation
employing CuSCN/4,4'-dimethoxy-2,2'-bipyridine as catalyst can be performed
without purification of the N-Cl intermediate.
PMID- 29956942
TI - Hydrated Phospholipid Polymer Gel-Like Layer for Increased Durability of
Orthopedic Bearing Surfaces.
AB - Recently, traditional strategies for manipulating orthopedic bearing substrates
have attempted to improve their wear resistance by adjusting polyethylene
substrate through cross-linking and antioxidant blending. However, further
research is required on the substrate, as well as the surface focused on the
structure and role of articular cartilage. We therefore develop an orthopedic
bearing surface comprising a nanometer-scale hydrated gel-like layer by grafting
highly hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine), with the aim
of mimicking the lubrication mechanism of articular cartilage, and investigate
its surface characteristics, bulk characteristics, and behavior under load
bearing conditions upon accelerated aging. Neither the hydrophilicity nor
lubricity of the gel-like surface was influenced by accelerated aging; instead,
high stability was revealed, even under strong oxidation conditions. The
characteristics of the hydrated gel-like surface potentiated the wear resistance
of the cross-linked polyethylene liner, irrespective of accelerated aging. These
results suggest that the hydrated gel-like surface enhances the longevity of
cross-linked polyethylene bearings even under load-bearing conditions.
Furthermore, the inflection point on the time series of wear can be a suitable
indicator of the durability of the life-long protectant. In conclusion, the
hydrated gel-like surface can positively increase orthopedic implant durability.
PMID- 29956943
TI - Correction to Copper-Promoted 6- endo-trig Cyclization of beta,gamma-Unsaturated
Hydrazones for the Synthesis of 1,6-Dihydropyridazines.
PMID- 29956944
TI - Disruption of Current Filaments and Isotropization of the Magnetic Field in
Counterstreaming Plasmas.
AB - We study the stability of current filaments produced by the Weibel, or current
filamentation, instability in weakly magnetized counterstreaming plasmas. It is
shown that a resonance exists between the current-carrying ions and a
longitudinal drift-kink mode that strongly deforms and eventually breaks the
current filaments. Analytical estimates of the wavelength, growth rate, and
saturation level of the resonant mode are derived and validated by three
dimensional particle-in-cell simulations. Furthermore, self-consistent
simulations of counterstreaming plasmas indicate that this drift-kink mode is
dominant in the slow down of the flows and in the isotropization of the magnetic
field, playing an important role in the formation of collisionless shocks.
PMID- 29956945
TI - Jet Topics: Disentangling Quarks and Gluons at Colliders.
AB - We introduce jet topics: a framework to identify underlying classes of jets from
collider data. Because of a close mathematical relationship between distributions
of observables in jets and emergent themes in sets of documents, we can apply
recent techniques in "topic modeling" to extract jet topics from the data with
minimal or no input from simulation or theory. As a proof of concept with parton
shower samples, we apply jet topics to determine separate quark and gluon jet
distributions for constituent multiplicity. We also determine separate quark and
gluon rapidity spectra from a mixed Z-plus-jet sample. While jet topics are
defined directly from hadron-level multidifferential cross sections, one can also
predict jet topics from first-principles theoretical calculations, with potential
implications for how to define quark and gluon jets beyond leading-logarithmic
accuracy. These investigations suggest that jet topics will be useful for
extracting underlying jet distributions and fractions in a wide range of contexts
at the Large Hadron Collider.
PMID- 29956946
TI - Kuramoto Model for Excitation-Inhibition-Based Oscillations.
AB - The Kuramoto model (KM) is a theoretical paradigm for investigating the emergence
of rhythmic activity in large populations of oscillators. A remarkable example of
rhythmogenesis is the feedback loop between excitatory (E) and inhibitory (I)
cells in large neuronal networks. Yet, although the EI-feedback mechanism plays a
central role in the generation of brain oscillations, it remains unexplored
whether the KM has enough biological realism to describe it. Here we derive a two
population KM that fully accounts for the onset of EI-based neuronal rhythms and
that, as the original KM, is analytically solvable to a large extent. Our results
provide a powerful theoretical tool for the analysis of large-scale neuronal
oscillations.
PMID- 29956947
TI - Experimental Evidence of Accelerated Seismic Release without Critical Failure in
Acoustic Emissions of Compressed Nanoporous Materials.
AB - The total energy of acoustic emission (AE) events in externally stressed
materials diverges when approaching macroscopic failure. Numerical and conceptual
models explain this accelerated seismic release (ASR) as the approach to a
critical point that coincides with ultimate failure. Here, we report ASR during
soft uniaxial compression of three silica-based (SiO_{2}) nanoporous materials.
Instead of a singular critical point, the distribution of AE energies is
stationary, and variations in the activity rate are sufficient to explain the
presence of multiple periods of ASR leading to distinct brittle failure events.
We propose that critical failure is suppressed in the AE statistics by mechanisms
of transient hardening. Some of the critical exponents estimated from the
experiments are compatible with mean field models, while others are still open to
interpretation in terms of the solution of frictional and fracture avalanche
models.
PMID- 29956948
TI - Differential Activity-Driven Instabilities in Biphasic Active Matter.
AB - Active stresses can cause instabilities in contractile gels and living tissues.
Here we provide a generic hydrodynamic theory that treats these systems as a
mixture of two phases of varying activity and different mechanical properties. We
find that differential activity between the phases causes a uniform mixture to
undergo a demixing instability. We follow the nonlinear evolution of the
instability and characterize a phase diagram of the resulting patterns. Our study
complements other instability mechanisms in mixtures driven by differential
adhesion, differential diffusion, differential growth, and differential motion.
PMID- 29956949
TI - Exploring the Function Space of Deep-Learning Machines.
AB - The function space of deep-learning machines is investigated by studying growth
in the entropy of functions of a given error with respect to a reference
function, realized by a deep-learning machine. Using physics-inspired methods we
study both sparsely and densely connected architectures to discover a layerwise
convergence of candidate functions, marked by a corresponding reduction in
entropy when approaching the reference function, gain insight into the importance
of having a large number of layers, and observe phase transitions as the error
increases.
PMID- 29956950
TI - Hysteresis Relation between Turbulence and Temperature Modulation during the Heat
Pulse Propagation into a Magnetic Island in DIII-D.
AB - The hysteresis relation between turbulence and temperature modulation during the
heat pulse propagation into a magnetic island is studied for the first time in
toroidal plasmas. Lissajous curves of the density fluctuation (n[over ~]/n) and
the electron temperature (T_{e}) modulation show that the (n[over ~]/n)
propagation is faster than the heat pulse propagation near the O point of the
magnetic island. This faster n[over ~]/n propagation is experimental evidence of
the turbulence spreading from the X point to the O point of the magnetic island.
PMID- 29956951
TI - Probing the Interface of a Phase-Separated State in a Repulsive Bose-Fermi
Mixture.
AB - We probe the interface between a phase-separated Bose-Fermi mixture consisting of
a small Bose-Einstein condensate of ^{41}K residing in a large Fermi sea of
^{6}Li. We quantify the residual spatial overlap between the two components by
measuring three-body recombination losses for variable strength of the
interspecies repulsion. A comparison with a numerical mean-field model highlights
the importance of the kinetic energy term for the condensed bosons in maintaining
the thin interface far into the phase-separated regime. Our results demonstrate a
corresponding smoothing of the phase transition in a system of finite size.
PMID- 29956952
TI - Quantum State Engineering of a Hubbard System with Ultracold Fermions.
AB - Accessing new regimes in quantum simulation requires the development of new
techniques for quantum state preparation. We demonstrate the quantum state
engineering of a strongly correlated many-body state of the two-component
repulsive Fermi-Hubbard model on a square lattice. Our scheme makes use of an
ultralow entropy doublon band insulator created through entropy redistribution.
After isolating the band insulator, we change the underlying potential to expand
it into a half-filled system. The final many-body state realized shows strong
antiferromagnetic correlations and a temperature below the exchange energy. We
observe an increase in entropy, which we find is likely caused by the many-body
physics in the last step of the scheme. This technique is promising for low
temperature studies of cold-atom-based lattice models.
PMID- 29956953
TI - Light Localization in Local Isomorphism Classes of Quasicrystals.
AB - We study a continuum of photonic quasicrystal heterostructures derived from local
isomorphism (LI) classes of pentagonal quasicrystal tilings. These tilings are
obtained by direct projection from a five-dimensional hypercubic lattice. We
demonstrate that, with the sole exception of the Penrose LI class, all other LI
classes result in degenerate, effectively localized states, with precisely
predictable and tunable properties (frequencies, frequency splittings, and
densities). We show that localization and tunability are related to a
mathematical property of the pattern known as "restorability," i.e., whether the
tiling can be uniquely specified given only a set of rules that fix all allowed
clusters smaller than some bound.
PMID- 29956954
TI - Exact Confirmation of 1D Nonlinear Fluctuating Hydrodynamics for a Two-Species
Exclusion Process.
AB - We consider current statistics for a two-species exclusion process of particles
hopping in opposite directions on a one-dimensional lattice. We derive an exact
formula for the Green's function as well as for a joint current distribution of
the model, and study its long time behavior. For a step-type initial condition,
we show that the limiting distribution is a product of the Gaussian and the
Gaussian unitary ensemble Tracy-Widom distributions. This is the first analytic
confirmation for a multicomponent system of a prediction from the recently
proposed nonlinear fluctuating hydrodynamics for one-dimensional systems.
PMID- 29956955
TI - Floquet Engineering of Optical Solenoids and Quantized Charge Pumping along
Tailored Paths in Two-Dimensional Chern Insulators.
AB - The insertion of a local magnetic flux, as the one created by a thin solenoid,
plays an important role in gedanken experiments of quantum Hall physics. By
combining Floquet engineering of artificial magnetic fields with the ability of
single-site addressing in quantum gas microscopes, we propose a scheme for the
realization of such local solenoid-type magnetic fields in optical lattices. We
show that it can be employed to manipulate and probe elementary excitations of a
topological Chern insulator. This includes quantized adiabatic charge pumping
along tailored paths inside the bulk, as well as the controlled population of
edge modes.
PMID- 29956957
TI - X-Ray Sum Frequency Diffraction for Direct Imaging of Ultrafast Electron
Dynamics.
AB - X-ray diffraction from molecules in the ground state produces an image of their
charge density, and time-resolved x-ray diffraction can thus monitor the motion
of the nuclei. However, the density change of excited valence electrons upon
optical excitation can barely be monitored with regular diffraction techniques
due to the overwhelming background contribution of the core electrons. We present
a nonlinear x-ray technique made possible by novel free electron laser sources,
which provides a spatial electron density image of valence electron excitations.
The technique, sum frequency generation carried out with a visible pump and a
broadband x-ray diffraction pulse, yields snapshots of the transition charge
densities, which represent the electron density variations upon optical
excitation. The technique is illustrated by ab initio simulations of transition
charge density imaging for the optically induced electronic dynamics in a donor
or acceptor substituted stilbene.
PMID- 29956958
TI - Universality and Quantum Criticality of the One-Dimensional Spinor Bose Gas.
AB - We investigate the universal thermodynamics of the two-component one-dimensional
Bose gas with contact interactions in the vicinity of the quantum critical point
separating the vacuum and the ferromagnetic liquid regime. We find that the
quantum critical region belongs to the universality class of the spin-degenerate
impenetrable particle gas which, surprisingly, is very different from the single
component case and identify its boundaries with the peaks of the specific heat.
In addition, we show that the compressibility Wilson ratio, which quantifies the
relative strength of thermal and quantum fluctuations, serves as a good
discriminator of the quantum regimes near the quantum critical point. Remarkably,
in the Tonks-Girardeau regime, the universal contact develops a pronounced
minimum, reflected in a counterintuitive narrowing of the momentum distribution
as we increase the temperature. This momentum reconstruction, also present at low
and intermediate momenta, signals the transition from the ferromagnetic to the
spin-incoherent Luttinger liquid phase and can be detected in current experiments
with ultracold atomic gases in optical lattices.
PMID- 29956956
TI - Limits on Light Weakly Interacting Massive Particles from the First 102.8 kg*day
Data of the CDEX-10 Experiment.
AB - We report the first results of a light weakly interacting massive particles
(WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array
immersed in liquid nitrogen at the China Jinping Underground Laboratory with a
physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved
limits of 8*10^{-42} and 3*10^{-36} cm^{2} at a 90% confidence level on spin
independent and spin-dependent WIMP-nucleon cross sections, respectively, at a
WIMP mass (m_{chi}) of 5 GeV/c^{2} are achieved. The lower reach of m_{chi} is
extended to 2 GeV/c^{2}.
PMID- 29956959
TI - Nanomechanical Characterization of the Kondo Charge Dynamics in a Carbon
Nanotube.
AB - Using the transversal vibration resonance of a suspended carbon nanotube as a
charge detector for its embedded quantum dot, we investigate the case of strong
Kondo correlations between a quantum dot and its leads. We demonstrate that even
when large Kondo conductance is carried at odd electron number, the charging
behavior remains similar between odd and even quantum dot occupations. While the
Kondo conductance is caused by higher order processes, a sequential tunneling
only model can describe the time-averaged charge. The gate potentials of the
maximum current and fastest charge increase display a characteristic relative
shift, which is suppressed at increased temperature. These observations agree
very well with models for Kondo-correlated quantum dots.
PMID- 29956960
TI - Strong Coupling Nature of the Excitonic Insulator State in Ta_{2}NiSe_{5}.
AB - We analyze the measured optical conductivity spectra using the density-functional
theory-based electronic structure calculation and density-matrix renormalization
group calculation of an effective model. We show that, in contrast to a
conventional description, the Bose-Einstein condensation of preformed excitons
occurs in Ta_{2}NiSe_{5}, despite the fact that a noninteracting band structure
is a band-overlap semimetal rather than a small band-gap semiconductor. The
system above the transition temperature is therefore not a semimetal but rather a
state of preformed excitons with a finite band gap. A novel insulator state
caused by the strong electron-hole attraction is thus established in a real
material.
PMID- 29956961
TI - Glassy Phonon Heralds a Strain Glass State in a Shape Memory Alloy.
AB - Shape memory strain glasses are frustrated ferroelastic materials with glasslike
slow relaxation and nanodomains. It is possible to change a NiCoMnIn Heusler
alloy from a martensitically transforming alloy to a nontransforming strain glass
by annealing, but minimal differences are evident in the short- or long-range
order above the transition temperature-although there is a structural relaxation
and a 0.18% lattice expansion in the annealed sample. Using neutron scattering we
find glasslike phonon damping in the strain glass but not the transforming alloy
at temperatures well above the transition. Damping occurs in the mode with
displacements matching the martensitic transformation. With support from first
principles calculations, we argue that the strain glass originates not with
transformation strain pinning but with a disruption of the underlying electronic
instability when disorder resonance states cross the Fermi level.
PMID- 29956962
TI - Finite Density Condensation and Scattering Data: A Study in phi^{4} Lattice Field
Theory.
AB - We study the quantum field theory of a charged phi^{4} field in lattice
regularization at finite density and low temperature in 2 and 4 dimensions with
the goal of analyzing the connection of condensation phenomena to scattering data
in a nonperturbative way. The sign problem of the theory at nonzero chemical
potential MU is overcome by using a worldline representation for the Monte Carlo
simulation. At low temperature we study the particle number as a function of MU
and observe the steps for 1-, 2-, and 3-particle condensation. We determine the
corresponding critical values MU_{n}^{crit}, n=1, 2, 3 and analyze their
dependence on the spatial extent L of the lattice. Linear combinations of the
MU_{n}^{crit} give the interaction energies in the 2- and 3-particle sectors and
their dependence on L is related to scattering data by Luscher's formula and its
generalizations to three particles. For two dimensions we determine the
scattering phase shift and for four dimensions the scattering length. We cross
check our results with a determination of the mass and the 2- and 3-particle
energies from conventional 2-, 4-, and 6-point correlators at zero chemical
potential. The letter demonstrates that the physics of condensation at finite
density and low temperature is closely related to scattering data of a quantum
field theory.
PMID- 29956963
TI - Controlling Surface Plasmons Through Covariant Transformation of the Spin
Dependent Geometric Phase Between Curved Metamaterials.
AB - General relativity uses curved space-time to describe accelerating frames. The
movement of particles in different curved space-times can be regarded as
equivalent physical processes based on the covariant transformation between
different frames. In this Letter, we use one-dimensional curved metamaterials to
mimic accelerating particles in curved space-times. The different curved shapes
of structures are used to mimic different accelerating frames. The different
geometric phases along the structure are used to mimic different movements in the
frame. Using the covariant principle of general relativity, we can obtain
equivalent nanostructures based on space-time transformations, such as the
Lorentz transformation and conformal transformation. In this way, many covariant
structures can be found that produce the same surface plasmon fields when excited
by spin photons. A new kind of accelerating beam, the Rindler beam, is obtained
based on the Rindler metric in gravity. Very large effective indices can be
obtained in such systems based on geometric-phase gradient. This general
covariant design method can be extended to many other optical media.
PMID- 29956964
TI - Holographic QCD in the Veneziano Limit at a Finite Magnetic Field and Chemical
Potential.
AB - We investigate QCD-like gauge theories at strong coupling at a finite magnetic
field B, temperature T, and quark chemical potential MU using the improved
holographic QCD model, including the full backreaction of the quarks in the
plasma. In addition to the phase diagram, we study the behavior of the quark
condensate as a function of T, B, and MU and discuss the fate of (inverse)
magnetic catalysis at a finite MU. In particular, we observe that inverse
magnetic catalysis exists only for small values of the chemical potential. The
speed of sound in this holographic quark-gluon plasma exhibits interesting
dependence on the thermodynamic parameters.
PMID- 29956965
TI - Nonlocal and Nonlinear Surface Plasmon Polaritons and Optical Spatial Solitons
Induced by the Thermocapillary Effect.
AB - We study the propagation of surface plasmon polaritons (SPPs) on a metal surface
which hosts a thin film of a liquid dielectric. The Ohmic losses that are
inherently present due to the coupling of SPPs to conductors' electron plasma,
induce temperature gradients and fluid deformation driven by the thermocapillary
effect, which lead to a nonlinear and nonlocal change of the effective dielectric
constant. The latter extends beyond the regions of highest optical intensity and
constitutes a novel thermally self-induced mechanism that affects the propagation
of the SPPs. We derive the nonlinear and nonlocal Schrodinger equation that
describes propagation of low intensity SPP beams, and show analytically and
numerically that it supports a novel optical spatial soliton excitation.
PMID- 29956966
TI - Extreme Small-Scale Clustering of Droplets in Turbulence Driven by Hydrodynamic
Interactions.
AB - We perform three-dimensional particle tracking measurements on droplets in a
turbulent airflow. The droplets display the well-known preferential concentration
of inertial particles, with an additional extreme clustering at the smallest
scales. We explain this additional clustering phenomenon theoretically based on a
Stokes-flow description of two spheres including their mutual hydrodynamic
interaction and a perturbative small-inertia expansion.
PMID- 29956967
TI - Reversible Aggregation and Colloidal Cluster Morphology: The Importance of the
Extended Law of Corresponding States.
AB - Cluster morphology of spherical particles interacting with a short-range
attraction has been extensively studied due to its relevance to many
applications, such as the large-scale structure in amorphous materials, phase
separation, protein aggregation, and organelle formation in cells. Although it
was widely accepted that the range of the attraction solely controls the fractal
dimension of clusters, recent experimental results challenged this concept by
also showing the importance of the strength of attraction. Using Monte Carlo
simulations, we conclusively demonstrate that it is possible to reduce the
dependence of the cluster morphology to a single variable, namely, the reduced
second virial coefficient, B_{2}^{*}, linking the local properties of colloidal
systems to the extended law of corresponding states. Furthermore, the cluster
size distribution exhibits two well-defined regimes: one identified for small
clusters, whose fractal dimension, d_{f}, does not depend on the details of the
attraction, i.e., small clusters have the same d_{f}, and another related to
large clusters, whose morphology depends exclusively on B_{2}^{*}, i.e., d_{f} of
large aggregates follows a master curve, which is only a function of B_{2}^{*}.
This physical scenario is confirmed with the reanalysis of experimental results
on colloidal-polymer mixtures.
PMID- 29956969
TI - Latent Space Purification via Neural Density Operators.
AB - Machine learning is actively being explored for its potential to design,
validate, and even hybridize with near-term quantum devices. A central question
is whether neural networks can provide a tractable representation of a given
quantum state of interest. When true, stochastic neural networks can be employed
for many unsupervised tasks, including generative modeling and state tomography.
However, to be applicable for real experiments, such methods must be able to
encode quantum mixed states. Here, we parametrize a density matrix based on a
restricted Boltzmann machine that is capable of purifying a mixed state through
auxiliary degrees of freedom embedded in the latent space of its hidden units. We
implement the algorithm numerically and use it to perform tomography on some
typical states of entangled photons, achieving fidelities competitive with
standard techniques.
PMID- 29956970
TI - Electromagnetic Helicity in Complex Media.
AB - Optical helicity density is usually discussed for monochromatic electromagnetic
fields in free space. It plays an important role in the interaction with chiral
molecules or nanoparticles. Here we introduce the optical helicity density in a
dispersive isotropic medium. Our definition is consistent with biorthogonal
Maxwell electromagnetism in optical media and the Brillouin energy density as
well as with the recently introduced canonical momentum and spin of light in
dispersive media. We consider a number of examples, including electromagnetic
waves in dielectrics, negative-index materials, and metals, as well as
interactions of light in a medium with chiral and magnetoelectric molecules.
PMID- 29956968
TI - Fusion Energy Output Greater than the Kinetic Energy of an Imploding Shell at the
National Ignition Facility.
AB - A series of cryogenic, layered deuterium-tritium (DT) implosions have produced,
for the first time, fusion energy output twice the peak kinetic energy of the
imploding shell. These experiments at the National Ignition Facility utilized
high density carbon ablators with a three-shock laser pulse (1.5 MJ in 7.5 ns) to
irradiate low gas-filled (0.3 mg/cc of helium) bare depleted uranium hohlraums,
resulting in a peak hohlraum radiative temperature ~290 eV. The imploding shell,
composed of the nonablated high density carbon and the DT cryogenic layer, is,
thus, driven to velocity on the order of 380 km/s resulting in a peak kinetic
energy of ~21 kJ, which once stagnated produced a total DT neutron yield of
1.9*10^{16} (shot N170827) corresponding to an output fusion energy of 54 kJ.
Time dependent low mode asymmetries that limited further progress of implosions
have now been controlled, leading to an increased compression of the hot spot. It
resulted in hot spot areal density (rhor~0.3 g/cm^{2}) and stagnation pressure
(~360 Gbar) never before achieved in a laboratory experiment.
PMID- 29956971
TI - Z_{N} Berry Phases in Symmetry Protected Topological Phases.
AB - We show that the Z_{N} Berry phase (Berry phase quantized into 2pi/N) provides a
useful tool to characterize symmetry protected topological phases with
correlation that can be directly computed through numerics of a relatively small
system size. The Z_{N} Berry phase is defined in a N-1-dimensional parameter
space of local gauge twists, which we call the "synthetic Brillouin zone," and an
appropriate choice of an integration path consistent with the symmetry of the
system ensures exact quantization of the Berry phase. We demonstrate the
usefulness of the Z_{N} Berry phase by studying two 1D models of bosons, SU(3)
and SU(4) Affleck-Kennedy-Lieb-Tasaki models, where topological phase transitions
are captured by Z_{3} and Z_{4} Berry phases, respectively. We find that the
exact quantization of the Z_{N} Berry phase at the topological transitions arises
from a gapless band structure (e.g., Dirac cones or nodal lines) in the synthetic
Brillouin zone.
PMID- 29956972
TI - Experimental Machine Learning of Quantum States.
AB - Quantum information technologies provide promising applications in communication
and computation, while machine learning has become a powerful technique for
extracting meaningful structures in "big data." A crossover between quantum
information and machine learning represents a new interdisciplinary area
stimulating progress in both fields. Traditionally, a quantum state is
characterized by quantum-state tomography, which is a resource-consuming process
when scaled up. Here we experimentally demonstrate a machine-learning approach to
construct a quantum-state classifier for identifying the separability of quantum
states. We show that it is possible to experimentally train an artificial neural
network to efficiently learn and classify quantum states, without the need of
obtaining the full information of the states. We also show how adding a hidden
layer of neurons to the neural network can significantly boost the performance of
the state classifier. These results shed new light on how classification of
quantum states can be achieved with limited resources, and represent a step
towards machine-learning-based applications in quantum information processing.
PMID- 29956973
TI - Persistence of Perfect Packing in Twisted Bundles of Elastic Filaments.
AB - It is generally understood that geometric frustration prevents maximal hexagonal
packings in uniform filament bundles upon twist. We demonstrate that a hexagonal
packed elastic filament bundle can preserve its order over a wide range of twist
due to a subtle counteraction of geometric expansion with elastic contraction.
Using x-ray scanning and by locating each filament in the bundle, we show the
remarkable persistence of order even as the twist is increased well above 360
degrees , by measuring the spatial correlation function across the bundle cross
section. We introduce a model which analyzes the combined effects of elasticity
including filament stretching and radial and hoop compression necessary to
explain this generic preservation of order observed with Hookean filaments.
PMID- 29956974
TI - Erratum: Investigating Neutron Polarizabilities through Compton Scattering on
^{3}He [Phys. Rev. Lett. 98, 232303 (2007)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.98.232303.
PMID- 29956975
TI - Spin Subdiffusion in the Disordered Hubbard Chain.
AB - We derive and study an effective spin model that explains the anomalous spin
dynamics in the one-dimensional Hubbard model with strong potential disorder.
Assuming that charges are localized, we show that spins are delocalized and their
subdiffusive transport originates from a singular random distribution of spin
exchange interactions. The exponent relevant for the subdiffusion is determined
by the Anderson localization length and the density of the electrons. Although
the analytical derivations are valid for low particle density, numerical results
for the full model reveal a qualitative agreement up to half filling.
PMID- 29956976
TI - Topological Triply Degenerate Points Induced by Spin-Tensor-Momentum Couplings.
AB - The recent discovery of triply degenerate points (TDPs) in topological materials
has opened a new perspective toward the realization of novel quasiparticles
without counterparts in quantum field theory. The emergence of such protected
nodes is often attributed to spin-vector-momentum couplings. We show that the
interplay between spin-tensor- and spin-vector-momentum couplings can induce
three types of TDPs, classified by different monopole charges (C=+/-2, +/-1, 0).
A Zeeman field can lift them into Weyl points with distinct numbers and charges.
Different TDPs of the same type are connected by intriguing Fermi arcs at
surfaces, and transitions between different types are accompanied by level
crossings along high-symmetry lines. We further propose an experimental scheme to
realize such TDPs in cold-atom optical lattices. Our results provide a framework
for studying spin-tensor-momentum coupling-induced TDPs and other exotic
quasiparticles.
PMID- 29956977
TI - Gravitational Waves from Binary Mergers of Subsolar Mass Dark Black Holes.
AB - We explore the possible spectrum of binary mergers of subsolar mass black holes
formed out of dark matter particles interacting via a dark electromagnetism. We
estimate the properties of these dark black holes by assuming that their
formation process is parallel to Population-III star formation, except that dark
molecular cooling can yield a smaller opacity limit. We estimate the binary
coalescence rates for the Advanced LIGO and Einstein telescope, and find that
scenarios compatible with all current constraints could produce dark black holes
at rates high enough for detection by Advanced LIGO.
PMID- 29956978
TI - Collective Lamb Shift of a Nanoscale Atomic Vapor Layer within a Sapphire Cavity.
AB - We measure the near-resonant transmission of light through a dense medium of
potassium vapor confined in a cell with nanometer thickness in order to
investigate the origin and validity of the collective Lamb shift. A complete
model including the multiple reflections in the nanocell reproduces accurately
the observed line shape. It allows the extraction of a density-dependent shift
and width of the bulk atomic medium resonance, deconvolved from the cavity
effect. We observe an additional, unexpected dependence of the shift with the
thickness of the medium. This extra dependence demands further experimental and
theoretical investigations.
PMID- 29956979
TI - What Drives Metal-Surface Step Bunching in Graphene Chemical Vapor Deposition?
AB - Compressive strain relaxation of a chemical vapor deposition (CVD) grown graphene
overlayer has been considered to be the main driving force behind metal surface
step bunching (SB) in CVD graphene growth. Here, by combining theoretical studies
with experimental observations, we prove that the SB can occur even in the
absence of a compressive strain, is enabled by the rapid diffusion of metal
adatoms beneath the graphene and is driven by the release of the bending energy
of the graphene overlayer in the vicinity of steps. Based on this new
understanding, we explain a number of experimental observations such as the
temperature dependence of SB, and how SB depends on the thickness of the graphene
film. This study also shows that SB is a general phenomenon that can occur in all
substrates covered by films of two-dimensional (2D) materials.
PMID- 29956980
TI - Generalization of Turbulent Pair Dispersion to Large Initial Separations.
AB - We present a generalization of turbulent pair dispersion to large initial
separations (etagammapi^{+}pi^{-} Decay Dynamics.
AB - Using a low background data sample of 9.7*10^{5} J/psi->gammaeta^{'}, eta^{'}
>gammapi^{+}pi^{-} events, which are 2 orders of magnitude larger than those from
the previous experiments, recorded with the BESIII detector at BEPCII, the decay
dynamics of eta^{'}->gammapi^{+}pi^{-} are studied with both model-dependent and
model-independent approaches. The contributions of omega and the rho(770)-omega
interference are observed for the first time in the decays eta^{'}
>gammapi^{+}pi^{-} in both approaches. Additionally, a contribution from the box
anomaly or the rho(1450) resonance is required in the model-dependent approach,
while the process specific part of the decay amplitude is determined in the model
independent approach.
PMID- 29956992
TI - Chaotic-Integrable Transition in the Sachdev-Ye-Kitaev Model.
AB - Quantum chaos is one of the distinctive features of the Sachdev-Ye-Kitaev (SYK)
model, N Majorana fermions in 0+1 dimensions with infinite-range two-body
interactions, which is attracting a lot of interest as a toy model for
holography. Here we show analytically and numerically that a generalized SYK
model with an additional one-body infinite-range random interaction, which is a
relevant perturbation in the infrared, is still quantum chaotic and retains most
of its holographic features for a fixed value of the perturbation and
sufficiently high temperature. However, a chaotic-integrable transition,
characterized by the vanishing of the Lyapunov exponent and spectral correlations
given by Poisson statistics, occurs at a temperature that depends on the strength
of the perturbation. We speculate about the gravity dual of this transition.
PMID- 29956991
TI - Totally Destructive Many-Particle Interference.
AB - In a general, multimode scattering setup, we show how the permutation symmetry of
a many-particle input state determines those scattering unitaries that exhibit
strictly suppressed many-particle transition events. We formulate purely
algebraic suppression laws that identify these events and show that the many
particle interference at their origin is robust under weak disorder and imperfect
indistinguishability of the interfering particles. Finally, we demonstrate that
all suppression laws so far described in the literature are embedded in the
general framework that we here introduce.
PMID- 29956986
TI - Measurement of the Effective Weak Mixing Angle in pp[over -]->Z/gamma^{*}
>l^{+}l^{-} Events.
AB - We present a measurement of the effective weak mixing angle parameter
sin^{2}theta_{eff}^{l} in pp[over -]->Z/gamma^{*}->MU^{+}MU^{-} events at a
center-of-mass energy of 1.96 TeV, collected by the D0 detector at the Fermilab
Tevatron Collider and corresponding to 8.6 fb^{-1} of integrated luminosity. The
measured value of sin^{2}theta_{eff}^{l}[MUMU]=0.23016+/-0.00064 is further
combined with the result from the D0 measurement in pp[over -]->Z/gamma^{*}
>e^{+}e^{-} events, resulting in sin^{2}theta_{eff}^{l}[comb]=0.23095+/-0.00040.
This combined result is the most precise measurement from a single experiment at
a hadron collider and is the most precise determination using the coupling of the
Z/gamma^{*} to light quarks.
PMID- 29956994
TI - Symmetry Transition Preserving Chirality in QCD: A Versatile Random Matrix Model.
AB - We consider a random matrix model which interpolates between the chiral Gaussian
unitary ensemble and the Gaussian unitary ensemble while preserving chiral
symmetry. This ensemble describes flavor symmetry breaking for staggered fermions
in 3D QCD as well as in 4D QCD at high temperature or in 3D QCD at a finite
isospin chemical potential. Our model is an Osborn-type two-matrix model which is
equivalent to the elliptic ensemble but we consider the singular value statistics
rather than the complex eigenvalue statistics. We report on exact results for the
partition function and the microscopic level density of the Dirac operator in the
epsilon regime of QCD. We compare these analytical results with Monte Carlo
simulations of the matrix model.
PMID- 29956993
TI - Origins of Extreme Liquid Repellency on Structured, Flat, and Lubricated
Hydrophobic Surfaces.
AB - There are currently three main classes of liquid-repellent surfaces: micro- or
nanostructured superhydrophobic surfaces, flat surfaces grafted with "liquidlike"
polymer brushes, and lubricated surfaces. Despite recent progress, the
mechanistic explanation for the differences in droplet behavior on such surfaces
is still under debate. Here, we measure the dissipative force acting on a droplet
moving on representatives of these surfaces at different velocities U=0.01-1
mm/s using a cantilever force sensor with submicronewton accuracy and correlate
it to the contact line dynamics observed using optical interferometry at high
spatial (micron) and temporal (<0.1 s) resolutions. We find that the dissipative
force-due to very different physical mechanisms at the contact line-is
independent of velocity on superhydrophobic surfaces but depends nonlinearly on
velocity for flat and lubricated surfaces. The techniques and insights presented
here will inform future work on liquid-repellent surfaces and enable their
rational design.
PMID- 29956996
TI - Practical Unitary Simulator for Non-Markovian Complex Processes.
AB - Stochastic processes are as ubiquitous throughout the quantitative sciences as
they are notorious for being difficult to simulate and predict. In this Letter,
we propose a unitary quantum simulator for discrete-time stochastic processes
which requires less internal memory than any classical analogue throughout the
simulation. The simulator's internal memory requirements equal those of the best
previous quantum models. However, in contrast to previous models, it only
requires a (small) finite-dimensional Hilbert space. Moreover, since the
simulator operates unitarily throughout, it avoids any unnecessary information
loss. We provide a stepwise construction for simulators for a large class of
stochastic processes hence directly opening the possibility for experimental
implementations with current platforms for quantum computation. The results are
illustrated for an example process.
PMID- 29956999
TI - Sensing Coherent Dynamics of Electronic Spin Clusters in Solids.
AB - We observe coherent spin exchange between identical electronic spins in the solid
state, a key step towards full quantum control of electronic spin registers in
room temperature solids. In a diamond substrate, a single nitrogen vacancy (NV)
center coherently couples to two adjacent S=1/2 dark electron spins via the
magnetic dipolar interaction. We quantify NV-electron and electron-electron
couplings via detailed spectroscopy, with good agreement to a model of strongly
interacting spins. The electron-electron coupling enables an observation of
coherent flip-flop dynamics between electronic spins in the solid state, which
occur conditionally on the state of the NV. Finally, as a demonstration of
coherent control, we selectively couple and transfer polarization between the NV
and the pair of electron spins. Our observations enable the realization of fast
quantum gate operations and quantum state transfer in a scalable, room
temperature, quantum processor.
PMID- 29956998
TI - Fragility of Charge Order Near an Antiferromagnetic Quantum Critical Point.
AB - We investigate the interplay between charge order and superconductivity near an
antiferromagnetic quantum critical point using sign-problem-free Quantum Monte
Carlo simulations. We establish that, when the electronic dispersion is particle
hole symmetric, the system has an emergent SU(2) symmetry that implies a
degeneracy between d-wave superconductivity and charge order with d-wave form
factor. Deviations from particle-hole symmetry, however, rapidly lift this
degeneracy, despite the fact that the SU(2) symmetry is preserved at low
energies. As a result, we find a strong suppression of charge order caused by the
competing, leading superconducting instability. Across the antiferromagnetic
phase transition, we also observe a shift in the charge order wave vector from
diagonal to axial. We discuss the implications of our results to the universal
phase diagram of antiferromagnetic quantum-critical metals and to the elucidation
of the charge order experimentally observed in the cuprates.
PMID- 29957000
TI - Universal Features of Metastable State Energies in Cellular Matter.
AB - Mechanical equilibrium states of cellular matter are overwhelmingly metastable
and separated from each other by topology changes. Using theory and simulations,
it is shown that for a wide class of energy functionals in 2D, including those
describing tissue cell layers, local energy differences between neighboring
metastable states as well as global energy differences between initial states and
ground states are governed by simple, universal relations. Knowledge of
instantaneous length of an edge undergoing a T1 transition is sufficient to
predict local energy changes, while the initial edge length distribution yields a
successful prediction for the global energy difference. An analytical
understanding of the model parameters is provided.
PMID- 29956997
TI - Atomic Source of Single Photons in the Telecom Band.
AB - Single atoms and atomlike defects in solids are ideal quantum light sources and
memories for quantum networks. However, most atomic transitions are in the
ultraviolet-visible portion of the electromagnetic spectrum, where propagation
losses in optical fibers are prohibitively large. Here, we observe for the first
time the emission of single photons from a single Er^{3+} ion in a solid-state
host, whose optical transition at 1.5 MUm is in the telecom band, allowing for
low-loss propagation in optical fiber. This is enabled by integrating Er^{3+}
ions with silicon nanophotonic structures, which results in an enhancement of the
photon emission rate by a factor of more than 650. Dozens of distinct ions can be
addressed in a single device, and the splitting of the lines in a magnetic field
confirms that the optical transitions are coupled to the electronic spin of the
Er^{3+} ions. These results are a significant step towards long-distance quantum
networks and deterministic quantum logic for photons based on a scalable silicon
nanophotonics architecture.
PMID- 29957001
TI - Machine Learning Detection of Bell Nonlocality in Quantum Many-Body Systems.
AB - Machine learning, the core of artificial intelligence and big data science, is
one of today's most rapidly growing interdisciplinary fields. Recently, machine
learning tools and techniques have been adopted to tackle intricate quantum many
body problems. In this Letter, we introduce machine learning techniques to the
detection of quantum nonlocality in many-body systems, with a focus on the
restricted-Boltzmann-machine (RBM) architecture. Using reinforcement learning, we
demonstrate that RBM is capable of finding the maximum quantum violations of
multipartite Bell inequalities with given measurement settings. Our results build
a novel bridge between computer-science-based machine learning and quantum many
body nonlocality, which will benefit future studies in both areas.
PMID- 29957002
TI - Testing the Universality of Free Fall towards Dark Matter with Radio Pulsars.
AB - The violation of the weak equivalence principle (EP) in the gravitational field
of Earth, described by the Eotvos parameter eta_{?}, was recently constrained to
the level |eta_{?}|?10^{-14} by the MICROSCOPE space mission. The Eotvos
parameter eta_{DM}, pertaining to the differential couplings of dark matter (DM)
and ordinary matter, was only tested to the level |eta_{DM}|?10^{-5} by the Eot
Wash group and lunar laser ranging. This test is limited by the EP-violating
driving force in the solar neighborhood that is determined by the galactic
distribution of DM. Here we propose a novel celestial experiment using the
orbital dynamics from radio timing of binary pulsars, and obtain a competing
limit on eta_{DM} from a neutron-star-white-dwarf (NS-WD) system, PSR J1713+0747.
The result benefits from the large material difference between the NS and the WD
and the large gravitational binding energy of the NS. If we can discover a binary
pulsar within ~10 pc of the galactic center, where the driving force is much
larger in the expected DM spike, precision timing will improve the test of the
universality of free fall towards DM and constrain various proposed couplings of
DM to the standard model by several orders of magnitude. Such a test probes the
hypothesis that gravity is the only long-range interaction between DM and
ordinary matter.
PMID- 29957003
TI - Indistinguishability of Elementary Systems as a Resource for Quantum Information
Processing.
AB - Typical elements of quantum networks are made by identical systems, which are the
basic particles constituting a resource for quantum information processing.
Whether the indistinguishability due to particle identity is an exploitable
quantum resource remains an open issue. Here we study independently prepared
identical particles showing that, when they spatially overlap, an operational
entanglement exists that can be made manifest by means of separated localized
measurements. We prove this entanglement is physical in that it can be directly
exploited to activate quantum information protocols, such as teleportation. These
results establish that particle indistinguishability is a utilizable quantum
feature and open the way to new quantum-enhanced applications.
PMID- 29957004
TI - Valley Physics in Non-Hermitian Artificial Acoustic Boron Nitride.
AB - The valley can serve as a new degree of freedom in the manipulation of particles
or waves in condensed matter physics, whereas systems containing combinations of
gain and loss elements constitute rich building units that can mimic non
Hermitian properties. By introducing gain and loss in artificial acoustic boron
nitride, we show that the acoustic valley states and the valley-projected edge
states display exotic behaviors in that they sustain either attenuated or
amplified wave propagation. Our findings show how non-Hermiticity introduces a
mechanism in tuning topological protected valley transports, which may have
significance in advanced wave control for sensing and communication applications.
PMID- 29957005
TI - Polarization-Resolved Study of High Harmonics from Bulk Semiconductors.
AB - The polarization property of high harmonics from gallium selenide is investigated
using linearly polarized midinfrared laser pulses. With a high electric field,
the perpendicular polarization component of the odd harmonics emerges, which is
not present with a low electric field and cannot be explained by the perturbative
nonlinear optics. A two-dimensional single-band model is developed to show that
the anisotropic curvature of an energy band of solids, which is pronounced in an
outer part of the Brillouin zone, induces the generation of the perpendicular odd
harmonics. This model is validated by three-dimensional quantum mechanical
simulations, which reproduce the orientation dependence of the odd-order
harmonics. The quantum mechanical simulations also reveal that the odd- and even
order harmonics are produced predominantly by the intraband current and interband
polarization, respectively. These experimental and theoretical demonstrations
clearly show a strong link between the band structure of a solid and the
polarization property of the odd-order harmonics.
PMID- 29957006
TI - First-Principles Approach to Model Electrochemical Reactions: Understanding the
Fundamental Mechanisms behind Mg Corrosion.
AB - Combining concepts of semiconductor physics and corrosion science, we develop a
novel approach that allows us to perform ab initio calculations under controlled
potentiostat conditions for electrochemical systems. The proposed approach can be
straightforwardly applied in standard density functional theory codes. To
demonstrate the performance and the opportunities opened by this approach, we
study the chemical reactions that take place during initial corrosion at the
water-Mg interface under anodic polarization. Based on this insight, we derive an
atomistic model that explains the origin of the anodic hydrogen evolution.
PMID- 29957007
TI - Inverse Interscale Transport of the Reynolds Shear Stress in Plane Couette
Turbulence.
AB - Interscale interaction between small-scale structures near the wall and large
scale structures away from the wall plays an increasingly important role with
increasing Reynolds number in wall-bounded turbulence. While the top-down
influence from the large- to small-scale structures is well known, it has been
unclear whether the small scales near the wall also affect the large scales away
from the wall. In this Letter we show that the small-scale near-wall structures
indeed play a role to maintain the large-scale structures away from the wall, by
showing that the Reynolds shear stress is transferred from small to large scales
throughout the channel. This is in contrast to the turbulent kinetic energy
transport which is from large to small scales. Such an "inverse" interscale
transport of the Reynolds shear stress eventually supports the turbulent energy
production at large scales.
PMID- 29957008
TI - Observation of Anomalous Meissner Screening in Cu/Nb and Cu/Nb/Co Thin Films.
AB - We have observed the spatial distribution of magnetic flux in Nb, Cu/Nb, and
Cu/Nb/Co thin films using muon-spin rotation. In an isolated 50-nm-thick Nb film,
we find a weak flux expulsion (Meissner effect) which becomes significantly
enhanced when adding an adjacent 40 nm layer of Cu. The added Cu layer exhibits a
Meissner effect (due to induced superconducting pairs) and is at least as
effective as the Nb to expel flux. These results are confirmed by theoretical
calculations using the quasiclassical Green's function formalism. An unexpected
further significant enhancement of the flux expulsion is observed when adding a
thin (2.4 nm) ferromagnetic Co layer to the bottom side of the Nb. This observed
cooperation between superconductivity and ferromagnetism, by an unknown
mechanism, forms a key ingredient for developing superconducting spintronics.
PMID- 29957009
TI - Quantum Anomaly and Thermodynamics of One-Dimensional Fermions with Three-Body
Interactions.
AB - We show that a system of three species of one-dimensional fermions, with an
attractive three-body contact interaction, features a scale anomaly directly
related to the anomaly of two-dimensional fermions with two-body contact forces.
We show, furthermore, that those two cases (and their multispecies
generalizations) are the only nonrelativistic systems with contact interactions
that display a scale anomaly. While the two-dimensional case is well known and
has been under study both experimentally and theoretically for years, the one
dimensional case presented here has remained unexplored. For the latter, we
calculate the impact of the anomaly on the equation of state, which appears
through the generalization of Tan's contact for three-body forces, and determine
the pressure at finite temperature. In addition, we show that the third-order
virial coefficient is proportional to the second-order coefficient of the two
dimensional two-body case.
PMID- 29957010
TI - Toward Heisenberg-Limited Rabi Spectroscopy.
AB - The use of entangled states was shown to improve the fundamental limits of
spectroscopy to beyond the standard-quantum limit. Here, rather than probing the
free evolution of the phase of an entangled state with respect to a local
oscillator, we probe the evolution of an initially separable two-atom register
under an Ising spin Hamiltonian with a transverse field. The resulting correlated
spin-rotation spectrum is twice as narrow as that of an uncorrelated rotation. We
implement this ideally Heisenberg-limited Rabi spectroscopy scheme on the optical
clock electric-quadrupole transition of ^{88}Sr^{+} using a two-ion crystal. We
further show that depending on the initial state, correlated rotation can occur
in two orthogonal subspaces of the full Hilbert space, yielding entanglement
enhanced spectroscopy of either the average transition frequency of the two ions
or their difference from the mean frequency. The use of correlated spin rotations
can potentially lead to new paths for clock stability improvement.
PMID- 29957011
TI - Evidence for Electronically Driven Ferroelectricity in a Strongly Correlated
Dimerized BEDT-TTF Molecular Conductor.
AB - By applying measurements of the dielectric constants and relative length changes
to the dimerized molecular conductor kappa-(BEDT-TTF)_{2}Hg(SCN)_{2}Cl, we
provide evidence for order-disorder type electronic ferroelectricity that is
driven by the charge order within the (BEDT-TTF)_{2} dimers and stabilized by a
coupling to the anions. According to our density functional theory calculations,
this material is characterized by a moderate strength of dimerization. This
system thus bridges the gap between strongly dimerized materials, often
approximated as dimer-Mott systems at 1/2 filling, and nondimerized or weakly
dimerized systems at 1/4 filling, exhibiting a charge order. Our results indicate
that intradimer charge degrees of freedom are of particular importance in
correlated kappa-(BEDT-TTF)_{2}X salts and can create novel states, such as
electronically driven multiferroicity or charge-order-induced quasi-one
dimensional spin liquids.
PMID- 29957012
TI - Hysteretic Percolation from Locally Optimal Individual Decisions.
AB - The emergence of large-scale connectivity underlies the proper functioning of
many networked systems, ranging from social networks and technological
infrastructure to global trade networks. Percolation theory characterizes network
formation following stochastic local rules, while optimization models of network
formation assume a single controlling authority or one global objective function.
In socioeconomic networks, however, network formation is often driven by
individual, locally optimal decisions. How such decisions impact connectivity is
only poorly understood to date. Here, we study how large-scale connectivity
emerges from decisions made by rational agents that individually minimize costs
for satisfying their demand. We establish that the solution of the resulting
nonlinear optimization model is exactly given by the final state of a local
percolation process. This allows us to systematically analyze how locally optimal
decisions on the microlevel define the structure of networks on the macroscopic
scale.
PMID- 29957013
TI - Order Out of Chaos: Slowly Reversing Mean Flows Emerge from Turbulently Generated
Internal Waves.
AB - We demonstrate via direct numerical simulations that a periodic, oscillating mean
flow spontaneously develops from turbulently generated internal waves. We
consider a minimal physical model where the fluid self-organizes in a convective
layer adjacent to a stably stratified one. Internal waves are excited by
turbulent convective motions, then nonlinearly interact to produce a mean flow
reversing on timescales much longer than the waves' period. Our results
demonstrate for the first time that the three-scale dynamics due to convection,
waves, and mean flow is generic and hence can occur in many astrophysical and
geophysical fluids. We discuss efforts to reproduce the mean flow in reduced
models, where the turbulence is bypassed. We demonstrate that wave intermittency,
resulting from the chaotic nature of convection, plays a key role in the mean
flow dynamics, which thus cannot be captured using only second-order statistics
of the turbulent motions.
PMID- 29957014
TI - Light-Enhanced Spin Fluctuations and d-Wave Superconductivity at a Phase
Boundary.
AB - Time-domain techniques have shown the potential of photomanipulating existing
orders and inducing new states of matter in strongly correlated materials. Using
time-resolved exact diagonalization, we perform numerical studies of pump
dynamics in a Mott-Peierls system with competing charge and spin density waves. A
light-enhanced d-wave superconductivity is observed when the system resides near
a quantum phase boundary. By examining the evolution of spin, charge, and
superconducting susceptibilities, we show that a subdominant state in equilibrium
can be stabilized by photomanipulating the charge order to allow
superconductivity to appear and dominate. This work provides an interpretation of
light-induced superconductivity from the perspective of order competition and
offers a promising approach for designing novel emergent states out of
equilibrium.
PMID- 29957016
TI - Inhibition of Programmed Necrosis Limits Infarct Size through Altered
Mitochondrial and Immune Responses in the Aged Female Rat Heart.
AB - Both advancing age and estrogen loss exacerbate acute myocardial infarction (AMI)
in the female heart. However, the mechanistic underpinnings of age-related
differences in cell death following ischemia/reperfusion (I/R) injury in females
and reductions in cardioprotective reserve capacity remains largely unexplored.
The aim of this study was to determine the efficacy of programmed necrosis
inhibition on infarct size reduction and preservation of LV function following
I/R injury with female aging. F344 rats were ovariectomized (OVX) at 15 mo and
studied at 24 mo (MO OVX) vs adult ovary-intact (6 mo). Following in vivo
coronary artery ligation (CAL; 55 min I and 2 or 6 hr R), Necrostatin-1 (nec-1;
3.5 mg/kg or 5.7 mg/kg) delivered upon R, significantly reduced infarct size by
37% and improved LV function in MO OVX (p<0.01). While age-associated elevations
in cyclophilin D and mitochondrial acetylation (p<0.001) were unaffected by nec
1, profound reductions in IL-1, IL-6, TNFalpha (p<0.05) and cardiac immune cell
infiltration were observed in MO OVX but not adult. We conclude that chronic
inflammation and postmenopausal estrogen-deficiency conspire to exacerbate AMI
through a mechanism involving exaggerated mitochondrial-mediated programmed
necrosis through receptor interacting protein 1 (RIP1) signaling. Modulatory
effects of PN inhibition on proinflammatory cytokine production following I/R
reveal a potentially important mechanistic target to restore and preserve cardiac
function in the ovariectomized aged female heart.
PMID- 29957015
TI - Voltage-gated Ca2+ channel activity modulates smooth muscle cell calcium waves in
hamster cremaster arterioles.
AB - Cremaster muscle arteriolar smooth muscle cells (SMCs) display inositol 1,4,5
trisphosphate receptor-dependent Ca2+ waves that contribute to global myoplasmic
Ca2+ concentration and myogenic tone. However, the contribution made by voltage
gated Ca2+ channels (VGCCs) to arteriolar SMC Ca2+ waves is unknown. We tested
the hypothesis that VGCC activity modulates SMC Ca2+ waves in pressurized (80
cmH2O/59 mmHg, 34 degrees C) hamster cremaster muscle arterioles loaded with Fluo
4 and imaged by confocal microscopy. Removal of extracellular Ca2+ dilated
arterioles (32 +/- 3 to 45 +/- 3 MUm, n = 15, P < 0.05) and inhibited the
occurrence, amplitude, and frequency of Ca2+ waves ( n = 15, P < 0.05),
indicating dependence of Ca2+ waves on Ca2+ influx. Blockade of VGCCs with
nifedipine (1 MUM) or diltiazem (10 MUM) or deactivation of VGCCs by
hyperpolarization of smooth muscle with the K+ channel agonist cromakalim (10
MUM) produced similar inhibition of Ca2+ waves ( P < 0.05). Conversely,
depolarization of SMCs with the K+ channel blocker tetraethylammonium (1 mM)
constricted arterioles from 26 +/- 3 to 14 +/- 2 MUm ( n = 11, P < 0.05) and
increased wave occurrence (9 +/- 3 to 16 +/- 3 waves/SMC), amplitude (1.6 +/-
0.07 to 1.9 +/- 0.1), and frequency (0.5 +/- 0.1 to 0.9 +/- 0.2 Hz, n = 10, P <
0.05), effects that were blocked by nifedipine (1 MUM, P < 0.05). Similarly, the
VGCC agonist Bay K8644 (5 nM) constricted arterioles from 14 +/- 1 to 8 +/- 1 MUm
and increased wave occurrence (3 +/- 1 to 10 +/- 1 waves/SMC) and frequency (0.2
+/- 0.1 to 0.6 +/- 0.1 Hz, n = 6, P < 0.05), effects that were unaltered by
ryanodine (50 MUM, n = 6, P > 0.05). These data support the hypothesis that Ca2+
waves in arteriolar SMCs depend, in part, on the activity of VGCCs. NEW &
NOTEWORTHY Arterioles that control blood flow to and within skeletal muscle
depend on Ca2+ influx through voltage-gated Ca2+ channels and release of Ca2+
from internal stores through inositol 1,4,5-trisphosphate receptors in the form
of Ca2+ waves to maintain pressure-induced smooth muscle tone.
PMID- 29957017
TI - Antifibrotic cardioprotection of berberine via downregulating myocardial IGF-1
receptor-regulated MMP-2/MMP-9 expression in diabetic rats.
AB - Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the
occurrence of diastolic dysfunction. Our previous studies have shown that
berberine, a natural alkaloid, attenuates cardiac ischemia-reperfusion injury in
diabetic rats. The aim of present study was to investigate the effects of long
term berberine treatment on cardiac remodeling in diabetic rats and the
underlying mechanisms. Diabetic rats induced by low-dose streptozotocin injection
combined with 8 wk of high-fat diet displayed significant cardiac matrix collagen
deposition and dysfunction, whereas berberine administration (200 mg.kg-1.day-1,
gavage 4 wk) significantly ameliorated cardiac fibrosis and dysfunction and
reduced cardiac IGF-1 receptor (IGF-1R) expression in diabetic rats.
Interestingly, IGF-1R expression was upregulated in cardiac fibroblasts isolated
from diabetic hearts or cultured in high-glucose conditions (30 mM). High glucose
treatment or IGF-1R overexpression increased matrix metalloproteinase (MMP)-2/MMP
9 expression, alpha-smooth muscle actin (alpha-SMA), and collagen type I
expression in cardiac fibroblasts. In contrast, berberine treatment significantly
inhibited IGF-1R expression and exerted an antifibrotic effect in high glucose
cultured cardiac fibroblasts, as manifested by decreased MMP-2/MMP-9, alpha-SMA,
and collagen type I expression, whereas IGF-1R siRNA plus berberine treatment did
not further enhance this antifibrotic effect compared with berberine treatment
alone. Taken together, long-term berberine treatment ameliorates cardiac fibrosis
and dysfunction by downregulating IGF-1R expression in cardiac fibroblasts and
subsequently reducing MMP-2/MMP-9, alpha-SMA, and collagen type I expression in
diabetic hearts. The findings suggest the therapeutic potential of berberine for
diabetic cardiomyopathy associated with cardiac fibrosis. NEW & NOTEWORTHY
Berberine downregulated IGF-1 receptor expression and matrix metalloproteinase
2/matrix metalloproteinase-9 levels in cardiac fibroblasts and thus inhibited
fibroblast differentiation and collagen overproduction in diabetic hearts,
suggesting a novel mechanism for antifibrotic cardioprotection of berberine in
type 2 diabetes.
PMID- 29957018
TI - Salubrinal Enhances Doxorubicin Sensitivity in Human Cholangiocarcinoma Cells
Through Promoting DNA Damage.
AB - Cholangiocarcinoma (CCA) is a highly malignant and aggressive tumor of the bile
duct that arises from epithelial cells. Chemotherapy is an important treatment
strategy for CCA patients, but its efficacy remains limited due to drug
resistance. Salubrinal, an inhibitor of eukaryotic translation initiation factor
2 alpha (eIF2alpha), has been reported to affect antitumor activities in cancer
chemotherapy. In this study, the authors investigated the effect of salubrinal on
the chemosensitivity of doxorubicin in CCA cells. They showed that doxorubicin
induces CCA cell death in a dose- and time-dependent manner. Doxorubicin triggers
reactive oxygen species (ROS) generation and induces DNA damage in CCA cells. In
addition, ROS inhibitor N-acetylcysteine (NAC) pretreatment inhibits doxorubicin
induced CCA cell death. Importantly, these data demonstrate a synergistic death
induction effect contributed by the combination of salubrinal and doxorubicin in
CCA cells. It is notable that salubrinal promotes doxorubicin-induced ROS
production and DNA damage in CCA cells. Taken together, these data suggest that
salubrinal enhances the sensitivity of doxorubicin in CCA cells through promoting
ROS-mediated DNA damage.
PMID- 29957019
TI - Arthroscopically Repaired Bucket-Handle Meniscus Tears: Patient Demographics,
Postoperative Outcomes, and a Comparison of Success and Failure Cases.
AB - Objective To define patient demographics, preoperative, and intraoperative
surgical variables associated with successful or failed repair of bucket-handle
meniscal tears. Design All patients who underwent arthroscopic repair of a bucket
handle meniscus tear at a single institution between May 2011 and July 2016 with
minimum 6-month follow-up were retrospectively identified. Patient demographic,
preoperative (including imaging), and operative variables were collected and
evaluated. A Kaplan-Meier curve was generated to demonstrate meniscus repair
survivorship. Results In total, 75 patients (78 knees) with an average age of
26.53 +/- 10.67 years met inclusion criteria. The average follow-up was 23.41 +/-
16.43 months. Fifteen knees (19.2%) suffered re-tear of the repaired meniscus at
an average 12.24 +/- 9.50 months postoperatively. Survival analysis demonstrated
93.6% survival at 6 months, 84.6% survival at 1 year, 78.4% survival at 2 years,
and 69.9% survival at 3 years. There was significant improvement from baseline to
time of final follow-up in all patient-reported outcome ( P < 0.05) except Marx
score ( P = 0.933) and SF-12 Mental Subscale ( P = 0.807). The absence of other
knee pathology (including ligament tear, contralateral compartment meniscal tear,
or cartilage lesions) noted intraoperatively was the only variable significantly
associated with repair failure ( P = 0.024). Concurrent anterior cruciate
ligament reconstruction (vs. no concurrent anterior cruciate ligament
reconstruction) trended toward significance ( P = 0.059) as a factor associated
with successful repair. Conclusions With the exception of the absence of other
knee pathology (including ligament tear, contralateral compartment meniscal tear,
or cartilage lesions) noted intraoperatively, no other variables were
significantly associated with re-tear. The results are relatively durable with
84.6% survival at 1 year. Surgeons should attempt meniscal repair when presented
with a bucket-handle tear.
PMID- 29957020
TI - Failure to Replicate the Effects of the High-Probability Instructional Sequence
on Feeding in Children With Autism and Food Selectivity.
AB - Behavioral intervention has positive effects on feeding problems of children with
autism and food selectivity (FS), and researchers have evaluated a variety of
specific behavioral interventions. Confidence in the effects of some specific
interventions on feeding such as the high-probability instructional sequence
(HPS) is limited by a lack of replication. Therefore, we assessed the generality
of the HPS by replicating the intervention in children with autism and FS.
Contrary to prior research, the HPS did not improve feeding responses for three
consecutive children enrolled in the study. We discuss the results in relation to
publishing failures to replicate without experimental control in applied behavior
analysis research.
PMID- 29957021
TI - Getting to the heart of myofibroblast differentiation-implications for scleraxis
in ECM remodeling and therapeutic targeting.
PMID- 29957023
TI - No Benefit of Diaphragm Pacing in Upper Motor Neuron-Dominant Forms of
Amyotrophic Lateral Sclerosis.
PMID- 29957022
TI - New roles of aldosterone and mineralocorticoid receptors in cardiovascular
disease: translational and sex-specific effects.
AB - Recent advances in the field of mineralocorticoid receptor (MR) and its ligand
aldosterone expanded the role of this hormone and its receptor far beyond their
initial function as a regulator of Na+ and K+ homeostasis in epithelial cells.
The symposium "New Roles of Aldosterone and Mineralocorticoid Receptors in
Cardiovascular Disease: Translational and Sex-Specific Effects" presented at the
38th World Congress of the International Union of Physiological Sciences (Rio de
Janeiro, Brazil) highlighted the contribution of extrarenal MRs to cardiovascular
disease. This symposium showcased how MRs expressed in endothelial, vascular
smooth muscle, and immune cells plays a critical role in the development of
vascular disease associated with aging, obesity, and chronic aldosterone
stimulation and demonstrated that MR antagonism prevents the acute renal
dysfunction and tubular injury induced by ischemia-reperfusion injury. It was
also shown that the adipocyte-derived hormone leptin is a new direct regulator of
aldosterone secretion and that leptin-mediated aldosterone production is a major
contributor to obesity-associated hypertension in women. Sex differences in the
role of aldosterone and of endothelial MR in the cardiovascular outcomes of
obesity were highlighted. This review summarizes these important emerging
concepts regarding the contribution of aldosterone and cell-specific MR to
cardiovascular disease in male and female subjects and further supports sex
specific benefits of MR antagonist drugs to be tested in additional populations.
PMID- 29957024
TI - Effect of Catalase or Alpha Lipoic Acid Supplementation in the Vitrification
Solution of Ovine Ovarian Tissue.
AB - AIM: The present study evaluates the effect of different concentrations of
antioxidants (catalase - CAT and alpha lipoic acid - ALA) on the follicular
activation and morphology, DNA damage, ROS production, and mitochondrial activity
in vitrified sheep ovarian tissue. METHODS: This experiment was divided into two
steps. First, ovarian fragments were distributed into the following treatments:
fresh tissue or control (CTR), incubation (INC), vitrification without
antioxidant (VWA), with CAT (10, 20, or 40 IU mL-1) or ALA (25, 50, or 100 MUM mL
1). After vitrification/warming, the fragments were additionally incubated for 24
hours and evaluated for morphology and follicular activation, as well as reactive
oxygen species (ROS) levels in the culture medium. For the second step, other
ovarian fragments were submitted to CTR, VWA, CAT40, and ALA100. After
vitrification/warming, the fragments were incubated for 24 hours and evaluated by
cell density of ovarian stroma, DNA damage, and mitochondrial and intracellular
ROS levels. RESULTS: The percentage of morphologically normal follicles in
vitrified ovarian tissue in the presence of ALA in all concentrations did not
differ (p > 0.05) from fresh tissue or CTRs. The percentage of activated
follicles was higher in ALA100 MUM mL-1 than those observed for the treatments
INC, CAT (40 IU mL-1), or ALA (25 or 50 MUM mL-1). The use of CAT affected (p <
0.05) the density of stromal cells (40 IU mL-1), ROS levels (10 and 20 IU mL-1),
as well as DNA damage revealed by (c)H2AX (40 IU mL-1). CONCLUSIONS: Although 100
MUM/mL of ALA did not alter intracellular ROS, this concentration reduced the
levels of ROS in the culture medium, preserved both the follicular morphology, as
well as the mitochondrial activity, promoted follicle activation, and protected
the follicles from DNA damage.
PMID- 29957025
TI - LATCH Score as a Predictor of Exclusive Breastfeeding at 6 Weeks Postpartum: A
Prospective Cohort Study.
AB - INTRODUCTION: Assessment of breastfeeding efficiency by objective means is
essential to increase the success of breastfeeding. AIMS AND OBJECTIVES: To study
the utility of LATCH score in predicting exclusive breastfeeding rates at 6 weeks
postpartum along with an optimum cutoff between January 2016 and June 2016.
MATERIALS AND METHODS: One hundred mother-infant dyads born of vaginal delivery
with gestational age >=37 weeks and singleton births were included with LATCH
scores assessed at birth and 48 hours/discharge and followed up at 6 weeks
postpartum. RESULTS: Sixty-two of 100 (62%) infants were exclusively
breastfeeding at 6 weeks. Mean LATCH scores at birth (7.17 +/- 1.13 versus 4.26
+/- 1.7, p = <0.0001) and 48 hours/discharge (9.22 +/- 1.01 versus 5.78 +/- 1.29,
p = <0.0001) were higher in mothers who were breastfeeding at 6 weeks. LATCH
score >=6 at birth had a sensitivity 93.5% and specificity 65.78% and these
mothers were 5.92 times more likely to be breastfeeding at 6 weeks. LATCH score
>=8 at 48 hours/discharge had a sensitivity 93.55% and specificity 92.1% with
these mothers being 9.28 times more likely to be breastfeeding at 6 weeks
postpartum. Receiver operating characteristic (ROC) for LATCH score at birth and
exclusive breastfeeding (EBF) at 6 weeks had an area under curve (AUC) 0.915
(cutoff >=5.5 sensitivity 93.5%, false positive rate-34.2%). ROC for LATCH score
at 48 hours/discharge and EBF 6 weeks had an AUC 0.979 (cutoff >=7.5 sensitivity
93.5%, false positive rate-7.9%). CONCLUSION: LATCH represents a simple, cost
effective tool capable of predicting breastfeeding as early as in the first 24
hours of life, especially in resource-limited settings.
PMID- 29957027
TI - Exploration of drug-response mechanism by integrating genetics and epigenetics
across cancers.
AB - AIM: To discover CpG island methylator phenotype (CIMP) as a predictor for cancer
drug-response mechanism. MATERIALS & METHODS: CIMP classification of 966 cancer
cell lines was determined according to identified copy number alteration and
differential methylation by DNA methylation profiles. CIMP-related drugs were
analyzed by analysis of variance. Tissue-cell-drug networks were developed to
predict drug response of individual samples. RESULTS & CONCLUSION: One hundred
and thirty-six copy number gain and 142 copy number loss cell lines were
classified into CIMP-high and CIMP-low groups, meanwhile 9 and 24 CIMP-associated
drugs were identified, respectively. Specially, breast invasive carcinoma samples
primarily composed by HCC1419 were predicted to be sensitive to GSK690693. The
study provides guidance for drug response in cancer therapy through genome-wide
DNA methylation.
PMID- 29957026
TI - Novel Application of 32P Brachytherapy: Treatment of Angiolymphoid Hyperplasia
with Eosinophilia in the Right Auricle with 8-Year Follow-Up.
AB - BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a distinctive
benign vascular disease that can be challenging to treat due to inconsistent
results for various treatment modalities such as surgical excision,
corticosteroids, radiotherapy, laser therapy, and other therapies, so novel
approaches are needed to improve treatment outcomes. MATERIALS AND METHODS: ALHE
on the right auricle of a 54-year-old Chinese woman underwent brachytherapy using
32P simple drug membranes for five times. The 32P brachytherapy involving simple
drug membranes of brachytherapy began by diluting a 32P solution with 0.9% NaCl
solution to produce a radioactivity of 69.2-74.7 MBq/mL(1.87-2.02 mCi/mL). The
drug membranes were removed between 48 and 72h after application. There were
intervals ranging from 65 to 72d between the membrane application periods, and
the last treatment was in June 2010. RESULTS: After the 32P brachytherapy, follow
up results over the course of 8 years were promising. The regional symptoms
disappeared, the right preauricular swelling decreased, the subcutaneous nodules
decreased in size, the exudate disappeared, and the skin appearance improved.
CONCLUSIONS: This case indicated that 32P brachytherapy may represent a novel
ALHE treatment method that produces a favorable long-term outcome.
PMID- 29957028
TI - Cellular target engagement: a new paradigm in drug discovery.
PMID- 29957029
TI - The Combining Effects of Cell-Free Circulating Tumor DNA of Breast Tumor to the
Noninvasive Prenatal Testing Results: A Simulating Investigation.
AB - Massively parallel sequencing of circulating fetal DNA in the plasma of pregnant
women is a common method for noninvasive prenatal testing (NIPT) of fetal trisomy
13, 18, and 21. However, circulating DNA is not restricted to pregnant women,
with increased levels of plasma DNA also frequently detected in the plasma of
cancer patients. Among pregnant women whose NIPT results were inconsistent with
the fetal karyotype, a small number of patients have subsequently been diagnosed
with a previously undetected malignancy. However, the extent to which circulating
tumor DNA (ctDNA) affects the results of NIPT is still unclear. We examined serum
from 50 nonpregnant women with breast tumors by NIPT. These samples were then
added to serum containing trisomy 13, 18, and 21 fetal DNA to figure out the
extent to which maternal tumors can interrupt NIPT results in pregnant women with
breast tumors. Concentrations of cell-free DNA (cfDNA) were higher in both
pregnant women and breast tumor patients, relative to nonpregnant healthy
controls. Among the 50 samples evaluated, 3 produced false positive NIPT results
for trisomy 13, 18, or 21, indicating that genomic copy number variations (CNVs)
had occurred. Simulation testing also showed that ctDNA can increase the standard
deviation of the associated z-scores, which lower absolute z-scores by decreasing
the proportion of circulating fetal DNA relative to total DNA. Of the 50 samples
tested, 9 fell within the equivocal range and 8 produced false negative results
for trisomy 13, 18, or 21. Data presented here show for the first time that ctDNA
is able to affect NIPT results in two ways. First, ctDNA can lead to false
positive results due to the detection of genomic CNVs in tumor DNA.
Alternatively, ctDNA can increase the likelihood of a false negative by
decreasing the proportion of circulating fetal DNA in serum.
PMID- 29957031
TI - Determining the Transcription Rates Yielding Steady-State Production of mRNA in
the Lac Genetic Switch of Escherichia coli.
AB - To elucidate the regulatory dynamics of the gene expression activation and
inactivation, an in silico biochemical model of the lac circuit in Escherichia
coli was used to evaluate the transcription rates that yield the steady-state
mRNA production in active and inactive states of the lac circuit. This result can
be used in synthetic biology applications to understand the limits of the genetic
synthesis. Since most genetic networks involve many interconnected components
with positive and negative feedback control, intuitive understanding of their
dynamics is often difficult to obtain. Although the kinetic model of the lac
circuit considered involves only a single positive feedback, the developed
computational framework can be used to evaluate supported ranges of other
reaction rates in genetic circuits with more complex regulatory networks. More
specifically, the inducible lac gene switch in E. coli is regulated by unbinding
and binding of the inducer-repressor complexes to or from the DNA operator to
switch the gene expression on and off. The dependency of mRNA production at
steady state on different transcription rates and the repressor complexes has
been studied by computer simulations in the Lattice Microbe software. Provided
that the lac circuit is in active state, the transcription rate is independent of
the inducer-repressor complexes present in the cell. In inactive state, the
transcription rate is dependent on the specific inducer-repressor complex bound
to the operator that inactivates the gene expression. We found that the repressor
complex with the largest affinity to the operator yields the smallest range of
the feasible transcription rates to yield the steady state while the lac circuit
is in inactive state. In contrast, the steady state in active state can be
obtained for any value of the transcription rate.
PMID- 29957032
TI - A Power-Performance Perspective to Multiobjective Electroencephalogram Feature
Selection on Heterogeneous Parallel Platforms.
AB - This article provides an insight on the power-performance issues related with the
CPU-GPU (Central Processing Unit-Graphics Processing Unit) parallel
implementations of problems that frequently appear in the context of applications
on bioinformatics and biomedical engineering. More specifically, we analyze the
power-performance behavior of an evolutionary parallel multiobjective
electroencephalogram feature selection procedure that evolves subpopulations of
solutions with time-demanding fitness evaluation. The procedure has been
implemented in OpenMP to dynamically distribute either subpopulations or
individuals among devices, and uses OpenCL to evaluate the fitness of the
individuals. The development of parallel codes usually implies to maximize the
code efficiency, thus optimizing the achieved speedups. To follow the same trend,
this article extends and provides a more complete analysis of our previous works
about the power-performance characteristics in heterogeneous CPU-GPU platforms
considering different operation frequencies and evolutionary parameters, such as
distribution of individuals, etc. This way, different experimental configurations
of the proposed procedure have been evaluated and compared with respect to a
master-worker approach, not only in runtime but also considering energy
consumption. The experimental results show that lower operating frequencies does
not necessarily mean lower energy consumptions since energy is the product of
power and time. Thus, we have observed that parallel processing not only reduces
the runtime, but also the energy consumed by the application despite a higher
instantaneous power. Particularly, the workload distribution among both CPU and
GPU cores provides the best runtime and very low energy consumption compared with
the values achieved by the same alternatives executed by only CPU threads.
PMID- 29957030
TI - DNA methylation of imprinted genes in Mexican-American newborn children with
prenatal phthalate exposure.
AB - AIM: Imprinted genes exhibit expression in a parent-of-origin-dependent manner
and are critical for child development. Recent limited evidence suggests that
prenatal exposure to phthalates, ubiquitous endocrine disruptors, can affect
their epigenetic dysregulation. MATERIALS & METHODS: We quantified DNA
methylation of nine imprinted gene differentially methylated regions by
pyrosequencing in 296 cord blood DNA samples in a Mexican-American cohort. Fetal
exposure was estimated by phthalate metabolite concentrations in maternal urine
samples during pregnancy. RESULTS: Several differentially methylated regions of
imprinted genes were associated with high molecular weight phthalates. The most
consistent, positive, and false discovery rate significant associations were
observed for MEG3. CONCLUSION: Phthalate exposure in utero may affect methylation
status of imprinted genes in newborn children.
PMID- 29957034
TI - Is Bucolic Life Bad for Chronic Obstructive Pulmonary Disease?
PMID- 29957033
TI - Signature Gene Identification of Cancer Occurrence and Pattern Recognition.
AB - To identify signature genes for the pathogenesis of cancer, which provides a
theoretical support for prevention and early diagnosis of cancer. The pattern
recognition method was used to analyze the genome-wide gene expression data,
which was collected from the The Cancer Genome Atlas (TCGA) database. For the
transcription of invasive breast carcinoma, lung adenocarcinoma, lung squamous
cell carcinoma, colon adenocarcinoma, renal clear-cell carcinoma, thyroid
carcinoma, and hepatocellular carcinoma of the seven cancers, the signature genes
were selected by means of a combination of statistical methods, such as
correlation, t-test, confidence interval, etc. Modeling by artificial neural
network model, the accuracy can be as high as 98% for the TCGA data and as high
as 92% for the Gene Expression Omnibus (GEO) independent data, the recognition
accuracy of stage I is more than 95%, which is higher compared with the previous
study. The common genes emerging in five cancers were obtained from the signature
genes of seven cancers, PID1, and SPTBN2. At the same time, we obtain three
common pathways of cancer by using Kyoto Encyclopedia of Genes and Genomes'
pathway analysis. A functional analysis of the pathways shows their close
relationship at the level of gene regulation, which indicted that the identified
signature genes play an important role in the pathogenesis of cancer and is very
important for understanding the pathogenesis of cancer and the early diagnosis.
PMID- 29957035
TI - Rare Cause of Respiratory Failure: A Twist in the Tale.
PMID- 29957036
TI - Unclassifiable Interstitial Lung Disease: Time to Shrink the Black Box.
PMID- 29957037
TI - Is It Time to Move on from Identifying Risk Factors for 30-Day Chronic
Obstructive Pulmonary Disease Readmission? A Call for Risk Prediction Tools.
PMID- 29957039
TI - Successful Deployment of Two Balloon-Expandable Stents Using an In-Stent
Bifurcating Approach.
PMID- 29957038
TI - Chronic Obstructive Pulmonary Disease Education in Pulmonary Rehabilitation. An
Official American Thoracic Society/Thoracic Society of Australia and New
Zealand/Canadian Thoracic Society/British Thoracic Society Workshop Report.
AB - According to the 2013 American Thoracic Society/European Respiratory Society
statement on pulmonary rehabilitation (PR), education to promote effective self
management is a cornerstone of this intervention. Despite education's stature
within PR, there is currently limited evidence supporting its overall efficacy,
and minimal evidence guiding its optimal design and delivery. This workshop was
convened to focus on the current state of education in PR for patients with
chronic obstructive pulmonary disease, who are the most common people referred to
PR. The workshop explored the learning needs and limitations of patients
participating in PR, promising design features (from work done outside of PR)
that may inform our approach to education, and professional development of PR
healthcare educators. Areas identified as needing development include: 1) outcome
assessment for the educational component; 2) screening patients for conditions
that will impede the learning process (anxiety, depression, cognitive deficits
and health literacy issues); 3) tailoring content and optimizing delivery of the
educational component; and 4) training PR professionals in their roles as
educators. By necessity, the workshop conclusions are painted in broad strokes.
However, with ongoing interest in improving quality through individualized
patient assessment, educational design innovations, and scientific scrutiny
comparable to that given to exercise training, the educational component of PR
may achieve effective self-management, leading to successful behavior change and
enhancement in health.
PMID- 29957040
TI - Boosting Clinical Decision-making: Machine Learning for Intensive Care Unit
Discharge.
PMID- 29957041
TI - Bilateral Lung Masses and Dyspnea in a Young Woman.
PMID- 29957042
TI - Perioperative Use of a Hybrid Closed Loop System in an Obese Patient With Type 1
Diabetes Undergoing Metabolic Surgery: Insights Into Changes in Insulin Delivery
and Sensitivity.
PMID- 29957043
TI - Indoor Air Quality Problems at Home, School, and Work.
PMID- 29957044
TI - Tetraiodothyroacetic acid (tetrac), integrin alphavbeta3 and disabling of immune
checkpoint defense.
PMID- 29957045
TI - Improving the utility of molecular scaffolds for medicinal and computational
chemistry.
PMID- 29957047
TI - Reply to: Reduced IFN-gamma in Patients with Pulmonary Nontuberculous
Mycobacterial Disease: Potentially Multiple Causes.
PMID- 29957048
TI - Unraveling the Mysteries of the Asthmatic Airway Epithelium.
PMID- 29957049
TI - Let's Talk about Sex: A Novel Mechanism by Which Estrogen Receptor beta Limits
Hypoxia-Inducible Factor Expression in Pulmonary Endothelial Cells.
PMID- 29957051
TI - July Highlights/Papers by Junior Investigators/NIH News.
PMID- 29957050
TI - Recombinant IFN-beta for Postseptic Acute Lung Injury-What's the Mechanism?
PMID- 29957052
TI - Reduced IFN-gamma in Patients with Pulmonary Nontuberculous Mycobacterial
Disease: Potentially Multiple Causes.
PMID- 29957053
TI - Platelets: Pivotal Player in Primary Sensitization to Allergen?
PMID- 29957054
TI - MMP28 in Idiopathic Pulmonary Fibrosis: Beyond the Extracellular Matrix.
PMID- 29957055
TI - Diet-induced beta-cell insulin resistance results in reversible loss of
functional beta-cell mass.
AB - Although convincing in genetic models, the relevance of beta-cell insulin
resistance in diet-induced type 2 diabetes (T2DM) remains unclear. Exemplified by
diabetes-prone, male, C57B1/6J mice being fed different combinations of Western
style diet, we show that beta-cell insulin resistance occurs early during T2DM
progression and is due to a combination of lipotoxicity and increased beta-cell
workload. Within 8 wk of being fed a high-fat, high-sucrose diet, mice became
obese, developed impaired insulin and glucose tolerances, and displayed
noncompensatory insulin release, due, at least in part, to reduced expression of
syntaxin-1A. Through reporter islets transplanted to the anterior chamber of the
eye, we demonstrated a concomitant loss of functional beta-cell mass. When mice
were changed from diabetogenic diet to normal chow diet, the diabetes phenotype
was reversed, suggesting a remarkable plasticity of functional beta-cell mass in
the early phase of T2DM development. Our data reinforce the relevance of diet
composition as an environmental factor determining different routes of diabetes
progression in a given genetic background. Employing the in vivo reporter islet
monitoring approach will allow researchers to define key times in the dynamics of
reversible loss of functional beta-cell mass and, thus, to investigate the
underlying, molecular mechanisms involved in the progression toward T2DM
manifestation.-Paschen, M., Moede, T., Valladolid-Acebes, I., Leibiger, B.,
Moruzzi, N., Jacob, S., Garcia-Prieto, C. F., Brismar, K., Leibiger, I. B.,
Berggren, P.-O. Diet-induced beta-cell insulin resistance results in reversible
loss of functional beta-cell mass.
PMID- 29957056
TI - Classic SRY-box protein SOX7 functions as a tumor suppressor regulating WNT
signaling and is methylated in renal cell carcinoma.
AB - SOX7 (SRY-related high mobility group box 7), a high mobility group protein, is
reported to be down-regulated in several cancer types, which indicates an
important role in tumorigenesis; however, its biologic role in renal cell
carcinoma (RCC) pathogenesis remains unknown. We studied the alterations and
functions of SOX7 in RCC. We detected its broad expression in multiple human
normal tissues, including kidney, but frequent down-regulation in RCC cell lines
and primary tumors. Promoter CpG methylation seems to directly mediate SOX7
silencing in RCC cells, which could be reversed by demethylation treatment. SOX7
methylation was detected in primary RCC tumors, but rarely in normal kidney
tissues. Restoration of SOX7 in silenced 786-O and A498 RCC cell lines inhibited
their cell growth by inducing G0/G1 arrest, whereas SOX7 knockdown promoted RCC
cell proliferation. We also found that SOX7 silencing resulted in the activation
of WNT signaling and the induction of epithelial to mesenchymal transition. In
conclusion, the current study demonstrates that SOX7 is frequently inactivated by
promoter CpG methylation in RCC and functions as a tumor suppressor by regulating
WNT signaling.-Wang, L., Fan, Y., Zhang, L., Li, L., Kuang, G., Luo, C., Li, C.,
Xiang, T., Tao, Q., Zhang, Q., Ying, J. Classic SRY-box protein SOX7 functions as
a tumor suppressor regulating WNT signaling and is methylated in renal cell
carcinoma.
PMID- 29957057
TI - ZBED6 negatively regulates insulin production, neuronal differentiation, and cell
aggregation in MIN6 cells.
AB - Zinc finger BED domain containing protein 6 ( Zbed6) has evolved from a
domesticated DNA transposon and encodes a transcription factor unique to
placental mammals. The aim of the present study was to investigate further the
role of ZBED6 in insulin-producing cells, using mouse MIN6 cells, and to evaluate
the effects of Zbed6 knockdown on basal beta-cell functions, such as morphology,
transcriptional regulation, insulin content, and release. Zbed6-silenced cells
and controls were characterized with a range of methods, including RNA
sequencing, chromatin immunoprecipitation sequencing, insulin content and
release, subplasma membrane Ca2+ measurements, cAMP determination, and
morphologic studies. More than 700 genes showed differential expression in
response to Zbed6 knockdown, which was paralleled by increased capacity to
generate cAMP, as well as by augmented sub-plasmalemmal calcium concentration and
insulin secretion in response to glucose stimulation. We identified >4000
putative ZBED6-binding sites in the MIN6 genome, with an enrichment of ZBED6
sites at upregulated genes, such as the beta-cell transcription factors v-maf
musculoaponeurotic fibrosarcoma oncogene homolog A and Nk6 homeobox 1. We also
observed altered morphology/growth patterns, as indicated by increased cell
clustering, and in the appearance of axon-like Neurofilament, medium polypeptide
and tubulin beta 3, class III-positive protrusions. We conclude that ZBED6 acts
as a transcriptional regulator in MIN6 cells and that its activity suppresses
insulin production, cell aggregation, and neuronal-like differentiation.-Wang,
X., Jiang, L., Wallerman, O., Younis, S., Yu, Q., Klaesson, A., Tengholm, A.,
Welsh, N., Andersson, L. ZBED6 negatively regulates insulin production, neuronal
differentiation, and cell aggregation in MIN6 cells.
PMID- 29957058
TI - Chemotherapy-generated cell debris stimulates colon carcinoma tumor growth via
osteopontin.
AB - Colon cancer recurrence after therapy, such as 5-fluorouracil (5-FU), remains a
challenge in the clinical setting. Chemotherapy reduces tumor burden by inducing
cell death; however, the resulting dead tumor cells, or debris, may paradoxically
stimulate angiogenesis, inflammation, and tumor growth. Here, we demonstrate that
5-FU-generated colon carcinoma debris stimulates the growth of a subthreshold
inoculum of living tumor cells in subcutaneous and orthotopic models. Debris
triggered the release of osteopontin (OPN) by tumor cells and host macrophages.
Both coinjection of debris and systemic treatment with 5-FU increased plasma OPN
levels in tumor-bearing mice. RNA expression levels of secreted phosphoprotein 1,
the gene that encodes OPN, correlate with poor prognosis in patients with
colorectal cancer and are elevated in chemotherapy-treated patients who
experience tumor recurrence vs. no recurrence. Pharmacologic and genetic ablation
of OPN inhibited debris-stimulated tumor growth. Systemic treatment with a
combination of a neutralizing OPN antibody and 5-FU dramatically inhibited tumor
growth. These results demonstrate a novel mechanism of tumor progression mediated
by OPN released in response to chemotherapy-generated tumor cell debris.
Neutralization of debris-stimulated OPN represents a potential therapeutic
strategy to overcome the inherent limitation of cytotoxic therapies as a result
of the generation of cell debris.-Chang, J., Bhasin, S. S., Bielenberg, D. R.,
Sukhatme, V. P., Bhasin, M., Huang, S., Kieran, M. W., Panigrahy, D. Chemotherapy
generated cell debris stimulates colon carcinoma tumor growth via osteopontin.
PMID- 29957059
TI - Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis
in cardiometabolic disorders.
AB - The disruption of systemic immune homeostasis is a key mediator in the
progression of cardiometabolic diseases (CMDs). We aimed to extend knowledge
regarding the clinical relevance of CMD-associated variation of circulating
mucosal-associated invariant T (MAIT) cell abundance and to explore underlying
cellular mechanisms. We analyzed cross-sectional data from 439 participants of
the Metagenomics in Cardiometabolic Diseases (MetaCardis) study, stratified into
6 groups: healthy control subjects and patients with metabolic syndrome (MS),
obesity, type 2 diabetes mellitus (T2DM), and coronary artery disease (CAD)
without, or with congestive heart failure (CAD-CHF). Blood MAIT cell frequency
was significantly decreased in all CMD groups, including early (MS) and later
(CAD and CAD-CHF) stages of disease progression. Reduced MAIT cell abundance was
associated with increased glycosylated hemoglobin, inflammation markers, and
deterioration of cardiac function. Glucose dose dependently promoted MAIT cell
apoptosis in vitro, independently of anti-CD3 and cytokine-mediated activation.
This outcome suggests the prominence of metabolic over an antigenic or cytokine
rich environment to promote MAIT cell reduction in patients with CMD. In summary,
all stages of CMDs are characterized by reduced circulating MAIT cells.
Chronically elevated blood glucose levels could contribute to this decline. These
data extend the pathologic relevance of MAIT cell loss and suggest that MAIT cell
abundance may serve as an indicator of cardiometabolic health.-Touch, S.,
Assmann, K. E., Aron-Wisnewsky, J., Marquet, F., Rouault, C., Fradet, M., Mosbah,
H., MetaCardis Consortium, Isnard, R., Helft, G., Lehuen, A., Poitou, C.,
Clement, K., Andre, S. Mucosal-associated invariant T (MAIT) cells are depleted
and prone to apoptosis in cardiometabolic disorders.
PMID- 29957060
TI - Transcriptional signatures for coupled predictions of stage II and III colorectal
cancer metastasis and fluorouracil-based adjuvant chemotherapy benefit.
AB - The current study suggests that the identification of predictive signatures of
fluorouracil (5-FU) response for stage II and III colorectal cancer (CRC) could
be confounded by chemotherapy-irrelevant low relapse risk. Using the samples of
patients with stage II and III CRC who were treated with curative surgery only,
we identified a signature with which to predict chemotherapy-irrelevant relapse
risk for patients after curative surgery. By applying this signature to the
samples of patients with stage II and III CRC who were treated with 5-FU-based
adjuvant chemotherapy (ACT) after surgery, we predicted the relapse risk if
treated with surgery only. From high-risk samples, we further identified another
signature with which to predict therapeutic benefit from 5-FU-based ACT. On the
basis of the relative expression orderings of gene pairs, a postsurgery relapse
risk signature that consisted of 44 gene pairs was developed and verified in 3
independent data sets. A 5-FU therapeutic benefit signature that consisted of 4
gene pairs was then developed to predict the response of 5-FU-based ACT for those
patients with high relapse risk after curative surgery. The signature was
verified in 4 independent datasets. For patients with stage II and III CRC, the
coupled signatures can first identify patients with high relapse risk after
curative surgery, then predict therapeutic benefit from 5-FU-based ACT.-Song, K.,
Guo, Y., Wang, X., Cai, H., Zheng, W., Li, N., Song, X., Ao, L., Guo, Z., Zhao,
W. Transcriptional signatures for coupled predictions of stage II and III
colorectal cancer metastasis and fluorouracil-based adjuvant chemotherapy
benefit.
PMID- 29957061
TI - Novel non-canonical regulation of soluble VEGF/VEGFR2 signaling by
mechanosensitive ion channel TRPV4.
AB - VEGF signaling via VEGF receptor-2 (VEGFR2) is a major regulator of endothelial
cell (EC) functions, including angiogenesis. Although most studies of
angiogenesis focus on soluble VEGF signaling, mechanical signaling also plays a
critical role. Here, we examined the consequence of disruption of mechanical
signaling on soluble signaling pathways. Specifically, we observed that small
interfering RNA (siRNA) knockdown of a mechanosensitive ion channel, transient
receptor potential vanilloid 4 (TRPV4), significantly reduced perinuclear (Golgi)
VEGFR2 in human ECs with a concomitant increase in phosphorylation at Y1175 and
membrane translocation. TRPV4 knockout (KO) ECs exhibited increased plasma
membrane localization of phospho-VEGFR2 compared with normal ECs. The knockdown
also increased phospho-VEGFR2 in whole cell lysates and membrane fractions
compared with control siRNA-treated cells. siRNA knockdown of TRPV4 enhanced
nuclear localization of mechanosensitive transcription factors, yes-associated
protein/transcriptional coactivator with PDZ-binding motif via rho kinase, which
were shown to increase VEGFR2 trafficking to the plasma membrane. Furthermore,
TRPV4 deletion/knockdown enhanced VEGF-mediated migration in vitro and increased
expression of VEGFR2 in vivo in the vasculature of TRPV4 KO tumors compared with
wild-type tumors. Our results thus show that TRPV4 channels regulate VEGFR2
trafficking and activation to identify novel cross-talk between mechanical
(TRPV4) and soluble (VEGF) signaling that controls EC migration and angiogenesis.
Kanugula, A. K., Adapala, R. K., Midha, P., Cappelli, H. C., Meszaros, J. G.,
Paruchuri, S., Chilian, W. M., Thodeti, C. K., Novel non-canonical regulation of
soluble VEGF/VEGFR2 signaling by mechanosensitive ion channel TRPV4.
PMID- 29957062
TI - LRRC8A is essential for swelling-activated chloride current and for regulatory
volume decrease in astrocytes.
AB - Consolidated evidence indicates that astroglial cells are critical in the
homeostatic regulation of cellular volume by means of ion channels and aquaporin
4. Volume-regulated anion channel (VRAC) is the chloride channel that is
activated upon cell swelling and critically contributes to cell volume regulation
in astrocytes. The molecular identity of VRAC has been recently defined,
revealing that it belongs to the leucine-rich repeat-containing 8 (LRRC8) protein
family. However, there is a lack of evidence demonstrating that LRRC8A underpins
VRAC currents in astrocyte. Nonetheless, direct evidence of the role of LRRC8A in
astrocytic regulatory volume decrease remains to be proved. Here, we aim to
bridge this gap in knowledge by combining RNA interference specific for LRRC8A
with patch-clamp analyses and a water-permeability assay. We demonstrated that
LRRC8A molecular expression is essential for swelling-activated chloride current
via VRAC in primary-cultured cortical astrocytes. The knockdown of LRRC8A with a
specific short interference RNA abolished the recovery of the cell volume after
swelling induced by hypotonic challenge. In addition, immunoblotting,
immunofluorescence, confocal imaging, and immunogold electron microscopy
demonstrated that LRRC8A is expressed in the plasma membrane of primary cortical
astrocytes and in situ in astrocytes at the perivascular interface with
endothelial cells. Collectively, our results suggest that LRRC8A is an essential
subunit of VRAC and a key factor for astroglial volume homeostasis.-Formaggio,
F., Saracino, E., Mola, M. G., Rao, S. B., Amiry-Moghaddam, M., Muccini, M.,
Zamboni, R., Nicchia, G. P., Caprini, M., Benfenati, V. LRRC8A is essential for
swelling-activated chloride current and for regulatory volume decrease in
astrocytes.
PMID- 29957063
TI - Synthesis and suggestion of a new nanometric gold(III) melatonin drug complex: an
interesting model for testicular protection.
AB - AIM: Melatonin (MLT) is a major hormone secreted by the pineal gland. In this
study, a gold(III) MLT (Au+3/MLT) complex has been synthesized and investigating
its protective effects against testicular damage. METHODOLOGY: The structural
features of the complex were investigated. For biological assessment, 30 male
rats were divided into three groups for 30 days. The first control group, the
second received MLT and the third received Au+3/MLT complex. RESULTS: The
Au+3/MLT complex was found to be nonelectrolytic with formula
(Au[MLT]2[Cl][H2O]). The ligand is monodentate and adopt square-planar geometry.
Its particles range in diameter from 35 to 100 nm. MLT affords slight oxidative
stress protection. The Au+3/MLT complex significantly decreases TNF-alpha and IL
1beta levels but elevates antioxidant enzyme capacities, reducing lipid
peroxidation markers and improving testicular histological structure. CONCLUSION:
The Au+3/MLT complex improves the anti-inflammatory actions of MLT, exhibits
potent antioxidant activity and enhances reproductive capacity.
PMID- 29957064
TI - Additive Effects of Intermittent Hypobaric Hypoxia and Endurance Training on
Bodyweight, Food Intake, and Oxygen Consumption in Rats.
AB - Cabrera-Aguilera, Ignacio, David Rizo-Roca, Elisa A. Marques, Garoa Santocildes,
Teresa Pages, Gines Viscor, Antonio A. Ascensao, Jose Magalhaes, and Joan Ramon
Torrella. Additive effects of intermittent hypobaric hypoxia and endurance
training on bodyweight, food intake, and oxygen consumption in rats. High Alt Med
Biol. 19:278-285, 2018.-We used an animal model to elucidate the effects of an
intermittent hypobaric hypoxia (IHH) and endurance exercise training (EET)
protocol on bodyweight (BW), food and water intake, and oxygen consumption.
Twenty-eight young adult male rats were divided into four groups: normoxic
sedentary (NS), normoxic exercised (NE), hypoxic sedentary (HS), and hypoxic
exercised (HE). Normoxic groups were maintained at an atmospheric pressure
equivalent to sea level, whereas the IHH protocol consisted of 5 hours per day
for 33 days at a simulated altitude of 6000 m. Exercised groups ran in normobaric
conditions on a treadmill for 1 hour/day for 5 weeks at a speed of 25 m/min. At
the end of the protocol, both hypoxic groups showed significant decreases in BW
from the ninth day of exposure, reaching final 10% (HS) to 14.5% (HE) differences
when compared with NS. NE rats also showed a significant weight reduction after
the 19th day, with a decrease of 7.4%. The BW of hypoxic animals was related to
significant hypophagia elicited by IHH exposure (from 8% to 12%). In contrast,
EET had no effect on food ingestion. Total water intake was not affected by
hypoxia but was significantly increased by exercise. An analysis of oxygen
consumption at rest (mL O2/[kg.min]) revealed two findings: a significant
decrease in both hypoxic groups after the protocol (HS, 21.7 +/- 0.70 vs. 19.1 +/
0.78 and HE, 22.8 +/- 0.80 vs. 17.1 +/- 0.90) and a significant difference at
the end of the protocol between NE (21.3 +/- 0.77) and HE (17.1 +/- 0.90). These
results demonstrate that IHH and EET had an additive effect on BW loss, providing
evidence that rats underwent a metabolic adaptation through a reduction in oxygen
consumption measured under normoxic conditions. These data suggest that the
combination of IHH and EET could serve as an alternative treatment for the
management of overweight and obesity.
PMID- 29957065
TI - Co-inhibition as a strategic therapeutic approach to overcome rifampin resistance
in tuberculosis therapy: atomistic insights.
AB - AIM: Amid the current global challenge of antimicrobial resistance, RNA
polymerase remains a paramount therapeutic target for tuberculosis. Dual binding
of rifampin (RIF) and a novel compound, DAAP1, demonstrated the suppression of
RIF resistance. However, a paucity of data elucidating the structural mechanism
of action of this synergistic interaction prevails. Methodology & results:
Molecular dynamic simulations unraveled the synergistic inhibitory
characteristics of DAAP1 and RIF. Co-binding induced a stable protein, increased
the degree of compactness of binding site residues around RIF and subsequently an
improved binding affinity toward RIF. CONCLUSION: Findings established the
structural mechanism by which DAAP1 stabilizes Mycobacterium tuberculosis RNA
polymerase, thus possibly suppressing RIF resistance. This study will assist
toward the design of novel inhibitors combating drug resistance in tuberculosis.
PMID- 29957066
TI - Is High Altitude a Risk Factor in Development of Herpes Zoster?
AB - : Singh, G.K., Mahendra Singh Deora, Rajan Grewal, A. Kushwaha, and Sukhmeet
Minhas. Is high altitude a risk factor in development of herpes zoster? High Alt
Med Biol. 19:244-248, 2018. BACKGROUND: Old age immune-compromised states are
known to increase the risk of herpes zoster (HZ). The aim of this study was to
find out whether arrival into high altitude poses a risk for the development of
HZ in lowlanders. METHODS: A retrospective study of 173 cases of HZ was carried
out between January 1, 2005 and December 31, 2010 in people working at high
altitude areas of Leh. Data of lowlander people working at high altitude were
compared with that of high altitude native and similar group of people working at
plains during the same period. RESULTS: HZ constitutes 2.36% (95% confidence
interval [CI], 2.04-2.73) of total skin outpatient department cases at a hospital
at high altitude, whereas it was 0.23% (95% CI, 0.18-0.29) at a tertiary hospital
at plains. In lowlanders working at high altitude, frequency of herpers zoster
varied between 2.63% and 3.59% with mean of 3.07%. Frequency of HZ in persons
presenting to a tertiary dermatological center at plains varied from 0.19% to
0.26% (mean of 0.23%). Presence of high altitude posed a risk of almost seven
times in developing HZ in comparison with its absence with odds ratio of 7.21 and
95% CI varying from 5.42 to 9.60. This result was statistically very significant
with p value <0.0001. CONCLUSIONS: Lowlanders working at high altitude are at
high risk to develop HZ in comparison with persons working at plains. However, a
large population-based study is required to investigate and establish the same.
PMID- 29957067
TI - Targeted Next Generation Sequencing Revealed Novel PRPF31 Mutations in Autosomal
Dominant Retinitis Pigmentosa.
AB - BACKGROUND: Retinitis pigmentosa (RP) is a rare type of inherited retinal
dystrophy that can result in progressive vision loss. Molecular diagnosis of RP
is challenging due to phenotypic and genotypic heterogeneities. AIMS: This study
aimed to identify the pathogenic mutations in two Chinese families with autosomal
dominant RP (adRP) and in a patient with sporadic RP. MATERIALS AND METHODS:
Peripheral blood DNA samples were obtained from the participants. Targeted next
generation sequencing (NGS) was applied to identify mutations in these patients.
For pathogenic mutation analyses, stringent NGS data analyses and segregation
analyses were applied. Primers were designed to validate the identified mutations
by Sanger sequencing analyses. RESULTS: A novel heterozygous insertion frameshift
mutation c.1226_1227insA, p.T410Dfs*65, and a novel heterozygous stopgain
mutation c.1015C>T, p.Q339* were identified in PRPF31. A known c.527 + 3A>G
splicing mutation was identified in one of the adRP-074 families. All mutations
were found to co-segregate with the disease, and none of these mutations were
detected in 500 control samples. CONCLUSIONS: Our data identified two new
autosomal dominant mutations in PRPF31, expanding the mutational spectrum of this
gene.
PMID- 29957068
TI - Identification of some benzoxazepines as anticancer agents inducing cancer cell
apoptosis.
AB - AIM: Using cytotoxic agents with apoptosis induction may represent one of new
strategies for cancer treatment to overcome the increased resistance of the
disease. METHODOLOGY: Two series of benzo[f][1,4]oxazepine-3,5(2H,4H)-diones
(compounds 5, 6a-f) and 3-phenylbenzo[f][1,4]oxazepin-5(4H)-ones (compounds 10,
11a-f) were synthesized and screened for their cytotoxicity against leukemia K
562 and breast T-47D cancer cell lines as well as normal fibroblasts WI-38.
RESULTS: The tested compounds revealed good cytotoxicity and selectivity toward
cancer cell lines relative to the normal cells, especially compounds 6f, 10 and
11e, f. These compounds were screened for cell cycle disturbance and apoptosis
induction. They were found to cause PreG1 apoptosis and complete cell growth
arrest at G2/M. They induce apoptosis via caspase-3 and Bax activation and
downregulation of Bcl2. CONCLUSION: benzo[f][1,4]oxazepine represents a scaffold
for further optimization to obtain promising anticancer agents.
PMID- 29957069
TI - Associations Between TP53 and MDM2 Polymorphisms and the Follicle-Stimulating
Hormone/Luteinizing Hormone Ratio in Infertile Women.
AB - AIMS: This is a follow-up study based on the results of our previous article, to
further explore the effect of the TP53 codon 72 (rs1042522) and MDM2 SNP309
(rs2279744) polymorphisms on basal follicle-stimulating hormone (FSH)/luteinizing
hormone (LH) ratios in infertility women. MATERIALS AND METHODS: The distribution
of two genetic polymorphisms (rs1042522 and rs2279744) and basal FSH/LH ratios
were tested and analyzed in 1051 in vitro fertilization (IVF) patients at a
university-affiliated hospital. RESULTS: The TP53 codon 72 polymorphism had a
significant association with the FSH/LH ratio (group I: FSH/LH <2.3 and group II:
FSH/LH >=2.3) (C/C vs. G/G: odds ratio [OR] = 1.69, 95% confidence interval [CI]:
1.07-2.65, p = 0.02; G/C vs. G/G: OR = 1.86, 95% CI: 1.25-2.77, p = 0.002). In a
stratification analysis, C allele carriers and the C/C genotype showed a strong
association with positive clinical pregnancy outcomes after IVF compared with G
allele carriers and the G/G genotype in the recessive, dominant, and allelic
genetic models in group I (C/C vs. G/G: OR = 1.84, 95% CI: 1.25-2.69, p = 0.01;
C/C vs. G carrier: OR = 1.52, 95% CI: 1.12-2.07, p = 0.01; C carrier vs. G/G: OR
= 1.46, 95% CI: 1.07-2.01, p = 0.02; C allele vs. G allele: OR = 1.34, 95% CI:
1.11-1.62, p = 0.003), no significant associations by stratification were
observed for group II. No associations were found between MDM2 SNP309 and either
of two groups. CONCLUSION: The TP53 codon 72 polymorphism is associated with
FSH/LH ratios, suggesting that it is a potential predictive genetic marker of IVF
outcome in patients younger than 35 years of age with baseline FSH levels below
10 IU/L and who have an FSH/LH ratio <2.3.
PMID- 29957070
TI - Antitubercular and anti-inflammatory properties screening of natural products
from Plectranthus species.
AB - AIM: Confirm the use of Plectanthus spp. plants in traditional medicine,
particularly as anti-inflammatory and anti-infective agents. MATERIALS & METHODS:
Compounds previously isolated from Plectranthus spp. were studied for their anti
inflammatory activity using the SNAP assay and RAW 264.7 cells, by the
quantification of nitric oxide. An halimane diterpene and its derivatives were
tested in infected macrophages with M. tuberculosis H37Rv, using CFU counts
assay, at their minimum inhibitory concentration values. Results: The isolated
compounds tested at noncytotoxic concentrations, did not reveal nitric oxide
scavenging in the S-nitroso-N-acetylpenicillamine and the cellular assays. On the
other hand, promising results were obtained regarding one semisynthetic halimane
derivative (11R*,13E)-halima-5,13-diene-11,15-diol), previously prepared (2.1 *
105 CFU/mL), with an effect similar to the antitubercular drugs ethambutol (2.0 *
105 CFU/mL) and isoniazid (1.2 * 105 CFU/mL). CONCLUSION: The present report
demonstrates the relevance of Plectranthus spp. in medicinal chemistry drug
development for TB and other infective respiratory complaints. Also, this work
suggests that further studies involving other inflammatory mediators are needed
to validate the anti-inflammatory use of these medicinal plants.
PMID- 29957072
TI - The importance of science communication in cancer research: an interview with
Martin Christlieb.
AB - I trained as a chemist, studying for a PhD at the University of Cambridge. After
I left Cambridge, I undertook postdoctoral appointments at Stanford and Oxford.
These appointments led me into metal chemistry, initially using the metals as
reagents, and finally using metal atoms as the key atom in a series of compounds
designed to be radiolabeled markers of tumor hypoxia for positron emission
tomography (PET) imaging. Finally I made the move to oncology to give my
compounds a chance to be tested in a more biological setting. I am now the public
engagement manager in the Department of Oncology at the University of Oxford,
where I look for opportunities to discuss our science with school students, adult
audiences and people who have been touched by cancer. During my spare time, I am
the Adventure Training Officer for Thames Valley RAF Air Cadets, where I work to
provide opportunities to allow young people to experience hill walking, climbing,
paddlesport, and trail cycling. I am a keen hill walker myself and recently, made
it to 6000 m in the Himalayas.
PMID- 29957071
TI - Association of the Interleukin-6 rs1800795 Polymorphism with Type 2 Diabetes
Mellitus in the Population of the Island of Crete, Greece.
AB - BACKGROUND: Interleukin 6 (IL-6), a proinflammatory cytokine, is elevated in
patients with type 2 diabetes (T2D), and is considered an independent predictor
of T2D. IL-6 single-nucleotide polymorphisms (SNPs) have been associated with
higher levels of IL-6. This study investigated the role of an IL-6 gene
polymorphism and its possible association to T2D in the genetically homogeneous
Greek population of the island of Crete. MATERIALS AND METHODS: A total of 144
patients with T2D and 180 controls, all Cretans, selected from the Diabetes
Clinic and the Department of Internal Medicine at the University Hospital of
Heraklion, Crete, Greece, were genotyped for the IL-6 -174G>C (rs1800795) SNP by
the restriction fragment length polymorphism method. RESULTS: The G/C genotype
and the minor allele C of the IL-6 rs1800795 SNP were more common in individuals
with T2D than controls (p = 0.004, odds ratio [OR] = 1.98, 95% confidence
interval [CI]: 1.24-3.18 and p = 0.011, OR = 1.59, 95% CI: 1.11-2.26,
respectively). CONCLUSION: An association of the rs1800795 SNP of the IL-6 gene
with T2D has been detected for the first time in Cretans. The present results, in
combination with those presented previously from different ethnic/racial
populations, highlight the necessity of comparative studies among different
ethnic/racial populations to detect genetic characteristics and associations with
T2D.
PMID- 29957073
TI - Eye function and physiology following a 161-km foot race.
AB - Significant visual impairment occurs in a small percentage of ultramarathon
participants and is thought to be due to corneal edema. Yet, the usual effects of
prolonged exercise on the eye have not been previously reported. Eight study
volunteers who completed the 161-km Western States Endurance Run underwent pre
race and post-race binocular and monocular visual acuity, intraocular pressure,
and corneal thickness measurements. None was symptomatic with visual impairment
during the race and they demonstrated no changes from pre-race to post-race in
visual acuity (p = 0.11-0.95 for right, left and combined), intraocular pressure
(p = 0.11-0.43 for the both eyes) and corneal thickness (p = 0.30-0.99 for both
eyes at three corneal areas). We conclude that there is no evidence that
ultramarathon running has an acute effect on eye function or physiology when the
runner has no symptoms or findings of visual impairment.
PMID- 29957074
TI - Impact of fibrates on circulating cystatin C levels: a systematic review and meta
analysis of clinical trials.
AB - AIMS: To assess the effect of fibrates on circulating cystatin C levels. MATERIAL
AND METHODS: Clinical studies evaluating the effect of a fibrate on circulating
cystatin C levels were searched in PubMed-Medline, SCOPUS, Web of Science, and
Google Scholar databases. A random-effect model and generic inverse variance
method were used for quantitative data synthesis, sensitivity analysis conducted
using the leave-one-out method, and weighted random-effects meta-regression
performed to evaluate potential confounders on cystatin C levels. RESULTS: This
meta-analysis of data from nine published studies (16 treatment arms) involved a
total of 2195 subjects. In a single-arm analysis of clinical trials (without
control group; eight studies comprising 14 treatment arms), fibrate therapy
increased circulating cystatin C concentrations (WMD: 0.07 mg/dL, 95% CI: 0.04,
0.10, p < .001; I2 = 82.66%). When the analysis was restricted to randomized
controlled trials (four studies comprising six treatment arms), again elevation
of circulating cystatin C levels was observed (WMD: 0.06 mg/L, 95% CI: 0.03,
0.09, p < .001; I2 = 42.98%). Elevated cystatin C levels were only seen with
fenofibrate and not with other fibrates. CONCLUSIONS: The results suggest that
fenofibrate treatment adversely affects cystatin C levels and might partially
explain the limited efficacy of fenofibrate in reducing cardiovascular events.
Key message Fenofibrate treatment adversely affects cystatin C levels and might
partially explain the limited efficacy of fenofibrate in reducing cardiovascular
events.
PMID- 29957075
TI - Proposal of an Extended Taxonomy of Serious Games for Health Rehabilitation.
AB - OBJECTIVE: Serious Games is a field of research that has evolved substantially
with valuable contributions to many application domains and areas. Patients often
consider traditional rehabilitation approaches to be repetitive and boring,
making it difficult for them to maintain their ongoing interest and assure the
completion of the treatment program. Since the publication of our first taxonomy
of Serious Games for Health Rehabilitation (SGHR), many studies have been
published with game prototypes in this area. Based on literature review, our goal
is to propose an updated taxonomy taking into account the works, updates, and
innovations in game criteria that have been researched since our first
publication in 2010. In addition, we aim to present the validation mechanism used
for the proposed extended taxonomy. MATERIALS AND METHODS: Based on a literature
review in the area and on the analysis of the contributions made by other
researchers, we propose an extended taxonomy for SGHR. For validating the
taxonomy proposal, a questionnaire was designed to use on a survey among experts
in the area. RESULTS: An extended taxonomy for SGHR was proposed. As we have
identified that, in general, and besides the mechanisms associated with the
adoption of a given taxonomy, there were no reported validation mechanisms for
the proposals, we designed a mechanism to validate our proposal. The mechanism
uses a questionnaire addressed to a sample of researchers and professionals with
experience and expertise in domains of knowledge interrelated with SGHR, such as
Computer Graphics, Game Design, Interaction Design, Computer Programming, and
Health Rehabilitation. CONCLUSION: The extended taxonomy proposal for health
rehabilitation serious games provides the research community with a tool to fully
characterize serious games. The mechanism designed for validating the taxonomy
proposal is another contribution of this work.
PMID- 29957076
TI - Triptorelin depot for the treatment of children 2 years and older with central
precocious puberty.
AB - INTRODUCTION: Triptorelin depot is largely used to treat central precocious
puberty (CPP) in children. Areas covered: This review updates triptorelin depot
treatment of CPP, focusing on trials that compared 3.75 mg/28 day treated and
untreated children till the adult height (AH). Efficacy of the new 11.25 mg/90
days or 22.5 mg/6 month formulations in suppressing pituitary-gonadal axis in
short-term trials is also addressed. Short- and long-term safety was summarized.
Expert commentary: Long experience on triptorelin depot use in children with CPP
is available. Outcome differences on AH are reported; they may be due to
heterogenicity of treated patients; some items remain to be optimized. No long
term-adverse events on reproductive function are reported; additional studies
would clarify if CPP per se or triptorelin depot administration may increase
hyperandrogenism and/or polycystic ovary syndrome risk in adulthood. The
quarterly formulation seems to be able to suppress pituitary-gonadal axis and
pubertal development and to determine similar end-results as monthly formulation,
but additional trials are needed. Few data are available for the 22.5 mg/6 month
formulation. Triptorelin depot treatment of CPP should be restricted to tertiary
pediatric endocrinology centers, considering that some uncertainties still exist
and that rare but serious adverse events may occur.
PMID- 29957077
TI - Factors influencing degree of hearing loss at presentation, hearing aid choice,
and usage in first time hearing aid users in Singapore.
AB - OBJECTIVE: To examine the factors associated with late presentation at first
hearing aid (HA) fitting, HA choice and usage among users in Singapore. DESIGN:
Retrospective cross-sectional study. STUDY SAMPLE: 1068 subjects issued with HAs
at a tertiary hospital from 2001 to 2013. RESULTS: Half of the subjects presented
with more severe (>55 dB) hearing loss (HL) in their better ear. In multivariable
analysis, older age, Malay ethnicity, conductive and mixed HL, and combination
type of HL were associated with more severe HL at first presentation. Over 70% of
subjects were older than 65 years. Worse pure tone audiometry (PTA) thresholds of
the better ear, gradual onset and sensorineural HL were associated with older age
presentation. For unilaterally fitted subjects, PTA thresholds were the only
determinant of having the better ear aided. Better PTA thresholds, younger age
and sensorineural HL were associated with choosing in ear compared to behind the
ear HAs. Younger age and worse PTA of the better ear were associated with >=4 h
of daily HA usage. CONCLUSIONS: Age, ethnicity and type of HL were important
determinants for more severe HL at first HA fitting. Older patients and those
with better hearing were less likely to use their HAs regularly.
PMID- 29957078
TI - Self-image after bariatric surgery and its relationship to gender, excess skin
and health-related quality of life.
AB - INTRODUCTION: There is limited knowledge about self-image in relation to excess
skin after bariatric surgery. The aim of this study was therefore to explore self
image after massive weight loss and its relationship to gender, weight loss,
discomfort regarding excess skin and health-related quality of life. METHODS:
Eighteen months after obesity surgery, 131 patients filled in questionnaires
about self-image (Som jag ser mig sjalv), excess skin (Sahlgrenska Excess Skin
Questionnaire, SESQ) and quality of life (EQ-5D and SF-36). In addition, maximal
ptosis was measured on their abdomen, arms and thighs. RESULTS: There were no
differences in self-image or quality of life between the genders. Participants
who scored low discomfort on SESQ had a significantly better overall self-image,
in all subscales, compared to those with high discomfort scores (p < .05). They
also had a significantly higher quality of life on the EQ-5D VAS (p = .045).
Correlations were low, if any, between self-image, excess skin, quality of life
and ptosis. There were moderate correlations between the SESQ score and the self
image subscore 'physical well-being', and in self-image and quality-of-life
scores. CONCLUSIONS: Self-image is lower among those who experience a high degree
of discomfort of excess skin after bariatric surgery. Its correlation to weight
loss, measured excess skin and quality of life is weak.
PMID- 29957079
TI - The perceived needs-access gap for health services among persons with
disabilities in a rural area within South Africa.
AB - PURPOSE: Health should be a universal phenomenon. However, little is known about
the relationship between disability status and health issues - particularly in
rural areas. This study looks at health issues of persons with disabilities in
Madwaleni, a rural impoverished area in South Africa in 2011, and compares them
to persons with no disabilities. MATERIALS AND METHODS: Standardized
questionnaires were used in the survey to assess disability and health status.
The sample comprised of 773 individuals - 322 persons with disability and 451
comparisons (without disability) - covering 527 households. Children under the
age of five were excluded from the sample. We used purposive sampling. RESULTS
AND CONCLUSION: This study found that persons with disabilities have poorer
reported health outcomes than persons with no disabilities. There is also an
association between disability severity and mental health issues as assessed by
the GHQ-12. A significantly higher percentage of persons with disability did not
get health care when needed. Persons with disabilities also have less favorable
attitudes toward competence of health care workers. This study has shown greater
health needs and less satisfaction with services, which strongly indicates
insufficient access for persons with disabilities in a rural impoverished are
within South Africa. Implications for rehabilitation Persons with disabilities in
rural South Africa have poorer reported health outcomes. Persons with
disabilities have less favorable attitudes towards competence of health care
workers in rural South Africa. Better access to health care for persons with
disabilities is needed in rural South Africa.
PMID- 29957080
TI - The psychometric properties of the toe tap test in people with stroke.
AB - OBJECTIVES: To investigate the: (i) inter-rater and test-retest reliability of
the toe tap test for people with stroke, (ii) the convergent validity of toe tap
test counts with stroke-specific impairments, (iii) minimum detectable change in
toe tap test counts, (iv) toe tap test cutoff counts which best discriminating
the performance between stroke survivors and healthy controls. DESIGN: Cross
sectional study. SETTING: University-based rehabilitation center. PARTICIPANTS:
Thirty-seven people with stroke and 35 healthy controls. MAIN OUTCOME MEASURES:
The toe tap test was administered along with the Fugl-Meyer lower extremity
assessment, muscle strength of ankle dorsiflexors and plantarflexors, five times
sit-to-stand test, Berg Balance Scale, limit of stability test, timed up and go
test, and Community Integration Measures questionnaire. RESULTS: Excellent inter
rater and test-retest reliabilities (intraclass correlation coefficient = 0.868
0.995 on the affected side) were found. A minimal detectable change of 8.7 counts
and a cutoff score of 21 counts was found on the affected side, while 12.6 counts
and 25 counts were found on the unaffected side, respectively. Toe tap test
counts on the affected side were significantly associated with Fugl-Meyer lower
extremity assessment scores, ankle muscle strength, Berg Balance Scale scores and
timed up and go test times. CONCLUSIONS: Toe tap test count on the affected side
is a simple and reliable tool for assessing ankle control in people with stroke.
Implications for rehabilitation Toe Tap Test counts have excellent intra-rater,
inter-rater, and test-retest reliabilities in people with stroke. Toe Tap Test
counts on the affected side were significantly associated with Fugl-Meyer
Assessment of Lower Extremity scores, ankle muscle strength, Berg Balance Scale
scores, and timed Up and Go test completion times. The 95% Minimal Detectable
Change for the Toe Tap Test counts was 8.7 counts of the affected side and 12.6
of the unaffected side. Toe Tap Test counts of 21 on the affected side and 25 on
the unaffected side (sensitivity 70.3-83.3%; specificity 71.4-85.7%) was found to
be the most representative for discriminating performance of Toe Tap Test in
chronic stroke survivors and healthy older adults. Toe Tap Test is a simple and
reliable tool for assessing ankle control in people with stroke.
PMID- 29957081
TI - Anticancer agent ABT-737 possesses anti-atopic dermatitis activity via blockade
of caspase-1 in atopic dermatitis in vitro and in vivo models.
AB - OBJECTIVE: Previous studies reported that depletion of Bcl-2 has a protective
effect against allergic diseases. Furthermore, recently our study showed that
anticancer drug has antiallergic inflammatory effect. An anticancer agent ABT-737
is an inhibitor of Bcl-2 and has an anti-inflammatory effect. However, the
antiallergic inflammatory activity of ABT-737 is still unknown. Here, we aimed to
explore the anti-atopic dermatitis (AD) activity and the mechanism of ABT-737 in
AD models. MATERIALS AND METHODS: HaCaT cells were used for in vitro experiments.
To evaluate the effect of ABT-737 in vivo model, BalB/c mice were orally
administered ABT-737 for 6 weeks in 2,4-dinitrofluorobenzene (DNFB)-induced AD
like murine model. Major assays were enzyme-linked immunosorbent assay, reverse
transcription-PCR, caspase-1 assay, histamine assay, and H&E staining. RESULTS:
ABT-737 significantly decreased thymic stromal lymphopoietin (TSLP) secretion and
caspase-1 activity in activated HaCaT cells. In DNFB-induced AD mice, oral
administration of ABT-737 alleviated clinical severity and scratching behavior.
ABT-737 decreased levels of AD-related biomarkers including IgE, histamine, TSLP,
and inflammatory cytokines. In addition, ABT significantly reduced caspase-1
activity in skin lesions of AD mice. DISCUSSION AND CONCLUSIONS: ABT-737 elicited
an anti-AD activity via suppression of caspase-1 activation in AD in vitro and in
vivo models. Therefore, this study provides important information regarding the
use of anticancer drugs for controlling allergic inflammatory diseases.
PMID- 29957082
TI - Serious Games for Children with Chronic Diseases: A Systematic Review.
AB - OBJECTIVE: The purpose of this study was to systematically review the literature
to assess if serious games impact health outcomes for children less than 18 years
of age with chronic diseases. Additionally, the impact of self-efficacy,
adherence, knowledge, use of theory, parent involvement, and study quality was
also examined. MATERIALS AND METHODS: Searches were conducted in databases EBSCO,
PubMed, and Web of Science between June and August 2016. Randomized controlled
trials using a serious game as an intervention, for participants under 18 years
of age, to improve their chronic disease were included. RESULTS: Data were
extracted by two independent researchers, including: Title, author, and
publication year; chronic disease; game description; number and age of
participants; intervention duration; significant findings; parent involvement;
theory; and study quality. Any disagreements were tackled and consensus was
achieved. Eighteen studies were included in the review. The areas of health
addressed included cerebral palsy, asthma, diabetes, developmental coordination
disorders, and vision disorders. In these articles, eight health outcome
variables were measured, including: lung function, glycemic control, hospital
visits, motor proficiency, and visual acuity. Psychosocial variables that were
assessed included self-efficacy and knowledge. Two articles included parents in
the intervention, and three articles used theory. Six studies had significant
health outcome finding, and four studies found a significant change in one
psychosocial variable. CONCLUSION: This review demonstrates the potential for
games to improve health outcomes of young individuals. However, the mixed results
suggest that more serious game interventions need to be better designed and
rigorously tested to support their impact on improving health outcomes.
PMID- 29957083
TI - How to predict response to anti-tumour necrosis factor agents in inflammatory
bowel disease.
AB - INTRODUCTION: Anti-tumor necrosis factor (TNF) agents have changed the
therapeutic approach to inflammatory bowel disease (IBD). However, a considerable
proportion of patients either do not primarily respond or lose response to
treatment. Despite the long-standing experience in the use of these drugs, still
there is the need of identifying the possible predictors of efficacy. Areas
covered: We critically review the current knowledge on predictors of response to
anti-TNF therapy - both those available in clinical practice and those still
under investigation. Multiple factors are involved in treatment success,
including disease phenotype and severity, adherence to medications, and
pharmacogenomic, pharmacokinetic, and immunologic factors. Literature search was
conducted in PubMed using keywords 'inflammatory bowel disease,' 'Crohn's
disease,' and 'ulcerative colitis,' matched with 'antitumor necrosis factor,'
'biologic therapy,' 'clinical response,' 'predictors,' and 'efficacy,' Relevant
articles were selected for review. Expert commentary: While the role of several
factors in clinical practice is clearly established, other investigational
markers have been proposed, mostly in small studies, yet for many of them little
external validation exists. Therapeutic drug monitoring is emerging as a pivotal
strategy to guide decisions in clinical practice. In the near future, novel
markers could improve our ability to direct treatment and personalize therapy.
PMID- 29957084
TI - Chronic abdominal pain in irritable bowel syndrome - current and future
therapies.
AB - INTRODUCTION: Irritable bowel syndrome (IBS) is a functional gut disorder that
typically manifests in early adult years. One of the two major symptoms of the
disease is chronic, visceral pain. The patients report pain as the most
distressing symptom with the greatest impact on quality of life, challenging both
to patients and healthcare providers. Areas covered: This review focuses on the
pathophysiology of abdominal pain in IBS and describes current treatment
possibilities. It also covers latest findings that may lead to novel
pharmacological options in IBS pain management. Expert commentary: Pain is the
main contributor to severity in IBS. Seeking pain alleviation is the most common
reason that IBS sufferers consult with their physicians. Not all patients report
being satisfied with available treatments for pain in IBS and there is a pressing
need to find new, more efficient therapies for this syndrome.
PMID- 29957085
TI - A Systematic Review of Bacterial Foodborne Outbreaks Related to Red Meat and Meat
Products.
AB - Our investigation focused on foodborne outbreaks related to meat and meat
products, published in peer-reviewed journals in the period 1980-2015. Most of
the outbreaks, investigated in this study, were caused by Escherichia coli and
Salmonella, causing 33 and 21 outbreaks, respectively, mostly in Europe and the
United States. In the E. coli outbreaks, the total number of reported cases was
1966, of which 1543 were laboratory confirmed. The number of cases requiring
hospitalization was 476, of whom 233 cases had a hemolytic-uremic syndrome (HUS),
and the reported deaths were 32. All of the E. coli outbreaks, except four, were
caused by serovar O157:H7. The other four outbreaks were caused by the following
serovars: O111:H8, O26:H11, O111, and O103:H25. Fresh processed meat products
were the category most frequently implicated. In the Salmonella outbreaks, the
total number of all reported cases was 2279, of whom 1891 were laboratory
confirmed. The number of reported cases requiring hospitalization was 94, and
seven were reported dead. Regarding Salmonella, eight serovars caused those
outbreaks. The most common serovar causing Salmonella-related outbreaks was
Salmonella Typhimurium. The food category most frequently implicated in those
outbreaks was raw-cured fermented sausages. Other organisms linked to meat
associated outbreaks, but less frequently reported, were Staphylococcus aureus,
Bacillus cereus, Clostridium perfringens, Clostridium botulinum, and Listeria
monocytogenes. Issues of the burden of outbreaks, the challenges of comparing
global outbreaks, food attribution, and how the meat industry works to meet
consumer demands while maintaining food safety are discussed.
PMID- 29957087
TI - Do Internet Users Lead a Healthier Lifestyle?
AB - Internet use has spread rapidly worldwide in recent years, but the proportion of
older people who use it remains low in Taiwan. Meanwhile, due to population aging
in the country, chronic diseases have become more prevalent among older people.
This study explores the link between exposure to the Internet and adoption of a
healthy lifestyle among the middle-aged and elderly people. Data are drawn from
the Topic on Health of the 2011 Taiwan Social Change Survey. We use the logistic
regression as the baseline model and apply the propensity-score weighting method
to identify the effect of Internet use on exercising, vegetable and fruit eating,
betel nut chewing, smoking, and heavy drinking. Our results show that people aged
40 years and older who use the Internet regularly are more likely to adopt an
overall healthy lifestyle. The findings suggest that the Internet is a good
channel to enhance people's health investment.
PMID- 29957088
TI - Genome of Serratia nematodiphila MB307 offers unique insights into its diverse
traits.
AB - A pigment-producing species of Serratia was isolated from the rhizosphere of a
heavy metal resistant Cannabis sativa plant growing in effluent-affected soil of
Hattar Industrial Estate, Haripur, Pakistan. Here, we report the genome sequence
of this bacterium, which has been identified as Serratia nematodiphila on the
basis of whole genome comparison using the OrthoANI classification scheme. The
bacterium exhibited diverse traits, including plant growth promotion,
antimicrobial, bioremediation, and pollutant tolerance capabilities including
metal tolerance, azo dye degradation, ibuprofen degradation, etc. Plant growth
promoting exoenzyme production as well as phosphate solubilisation properties
were observed. Genes for phosphate solubilisation, siderophore production, and
chitin destruction were identified in addition to other industrially important
enzymes like nitrilase and lipase. Secondary metabolite producing apparatus for
high value chemicals in the whole genome was also analysed. The number of
antibiotic resistance genes was then profiled in silico, through a match with
Antibiotic Resistant Gene and CAR database. This is the first report of a S.
nematodiphila genome from a polluted environment. This could significantly
contribute to the understanding of pollution tolerance, antibiotic resistance,
association with nematodes, production of bio-pesticide, and their role in plant
growth promotion.
PMID- 29957086
TI - What do people know about fertility? A systematic review on fertility awareness
and its associated factors.
AB - INTRODUCTION: Recent evidence indicates that reproductive-age people have
inadequate fertility awareness (FA) concerning fertility, infertility risk
factors, and consequences of delaying childbearing. However, no study has tried
to summarize these studies and to clarify the variables associated with FA,
namely the role of gender, age, education, and reproductive status on FA.
METHODS: A literature search up to February 2017 was conducted using the EBSCO,
Web of Science, Scielo, and Scopus electronic databases with combinations of
keywords and MeSH terms (e.g. 'awareness' OR 'health knowledge, attitudes,
practice' AND 'fertility'; 'fertile period'; 'assisted reprod*'). RESULTS:
Seventy-one articles met the eligibility criteria and were included. The main
results showed that participants report low-to-moderate FA. Higher levels of FA
were shown by women, highly educated individuals, people who reported
difficulties with conceiving, and those who had planned their pregnancies. Having
or desiring to have children was not related to FA level. An inconsistent
association between study participant age and FA was observed, with some studies
indicating that older participants had higher FA, but others found an opposite
result or did not find any association. CONCLUSION: The current findings suggest
that interventions to increase FA are warranted, especially those targeting men,
people with low education, and in family planning settings. Interventions and
campaigns should be customized to meet individuals' needs regarding FA. Because
of the high heterogeneity regarding the assessment of FA, these conclusions must
be interpreted with caution.
PMID- 29957089
TI - Games for Health: The Tale of a Curious Student's Wish.
PMID- 29957090
TI - 'J' brachioplasty technique in massive weight loss patients.
AB - Upper extremity body reshaping is a very frequent surgical procedure in massive
weight loss patients. Many surgeons have presented different patterns of
brachioplasty skin excision and a variety of adjunctive techniques, each of them
claiming improvements in scar aesthetic, arm shape or overall safety of the
procedure. In this pape,r we want to illustrate our personal brachioplasty
technique for massive weight loss patients. Our incision design named 'J'
Brachioplasty is described. Between March 2013 and March 2016, a retrospective
study of patients with massive weight loss and clinical diagnosis of brachial
ptosis undergoing surgical reconstruction with 'J' brachioplasty was performed.
All patients were treated according to a standard surgical procedure described in
detail in the paper. The presence of axillary and thoracic skin excess was also
recorded for every subject, as well as clinical and surgical postoperative
complications. A total number of 73 Caucasian underwent J-shaped brachioplasty.
Our technique allowed us to treat both arm and thoracic skin excess with a single
skin incision. Among our casuistic we had only two cases of postoperative
bleeding and four cases of partial wound dehiscence due to tension. Seroma was
reported only in one (female) patient. Despite the recent introduction our
technique has proven to reach good results in massive weight loss patients.
PMID- 29957091
TI - Is Curcumin a Possibility to Treat Inflammatory Bowel Diseases?
AB - The inflammatory bowel diseases (IBDs) are mainly represented by Crohn's disease
and Ulcerative colitis that are characterized by chronic and relapsing
inflammatory processes of the gastrointestinal system. Curcuma longa L. is a
plant with several medicinal properties, including anti-inflammatory effects, and
curcumin is the most important compound derived from its rhizomes. As curcumin
has remarkable anti-inflammatory actions, the aim of this work is to review the
potential use of this compound in IBD patients. We consulted MEDLINE
(PubMed/PMC), and the literature search was performed with the following
combinations of terms "Inflammatory Bowel Diseases" and "Curcumin," "Crohn's
Disease" and "Curcumin," "Ulcerative colitis" and "Curcumin." The inclusion
criteria were articles that showed original studies with human models and the
exclusion criteria were not full-text articles, articles not in English, poster
presentations, letters, editorials, and articles not available. Curcumin
interacts with receptors, growth and transcription factors, cytokines, enzymes,
and genes leading to inhibitory effects on cyclooxygenase-1, tumor necrosis
factor-alpha, interferon-gamma, inducible nitric oxide synthase, transcriptional
nuclear factor kappa B, and many other molecules associated with inflammatory
processes. These molecules are critical factors in the positive regulation of
inflammatory cytokines in inflammatory diseases, suggesting that curcumin may be
considered as a new therapeutic agent for patients with IBD. Curcumin is a
natural anti-inflammatory agent that represents an attractive, safe and
inexpensive alternative for the treatment of IBD. Nevertheless, it is necessary
to know the efficient and safe dose and consider its poor absorption.
PMID- 29957092
TI - Human Papillomavirus Vaccination Initiation Among Sexual Orientation Identity and
Racial/Ethnic Subgroups of Black and White U.S. Women and Girls: An
Intersectional Analysis.
AB - INTRODUCTION: Human papillomavirus (HPV) vaccination, which is recommended for
U.S. women and girls aged 11-26 years, effectively prevents cervical cancer.
Researchers have identified HPV vaccination disparities among groups of women and
girls defined in relation to sexual orientation identity or race/ethnicity.
However, no study has used an intersectional approach to ascertain HPV vaccine
uptake among sexual orientation identity and racial/ethnic subgroups of U.S.
women and girls. METHODS: Using 2011-2015 National Survey of Family Growth data,
we used multivariable logistic regression to estimate differences in the odds of
HPV vaccination initiation (i.e., >= one dose) across sexual orientation identity
and racial/ethnic subgroups of black and white U.S. women aged 15-24 years (N =
2,413), adjusting for demographic factors. We also assessed whether socioeconomic
and health care factors helped explain observed disparities. RESULTS: The overall
prevalence of HPV vaccination initiation was 47.7%. Compared to white
heterosexual women, black lesbians (odds ratio [OR] = 0.16; 95% confidence
interval [95% CI]: 0.06-0.46) had the lowest adjusted odds of HPV vaccination
initiation, followed by white lesbians (OR = 0.33; 95% CI: 0.13-0.82) and black
heterosexual women (OR = 0.63; 0.47-0.85). Including socioeconomic factors in the
model only slightly attenuated the HPV vaccination initiation odds ratios for
black lesbians (OR = 0.19; 95% CI: 0.06-0.56), white lesbians (OR = 0.37; 95% CI:
0.15-0.90), and black heterosexual women (OR = 0.70; 95% CI: 0.52-0.93) compared
to white heterosexual women. Adding health care factors only slightly
additionally attenuated the odds ratio comparing black lesbians and white
heterosexual women (OR = 0.21; 95% CI: 0.07-0.67). CONCLUSIONS: Our findings
identified black lesbians as a particularly underserved subgroup and suggest that
sexual orientation identity and race/ethnicity may have a compounding effect on
HPV vaccination initiation among black and white U.S. women and girls. Evidence
based interventions that are adapted to the specific needs and experiences of
black lesbians and other multiply marginalized groups are needed to promote
equity in HPV-related outcomes.
PMID- 29957093
TI - Religiosity and Health: A Holistic Biopsychosocial Perspective.
AB - The resurgence of interest in the influence of religion and spirituality on
health is examined within the context of the holistic paradigm and historical
connection between nursing and spirituality. While nursing and spirituality often
intersect with end-of-life considerations, this article presents findings from
studies that demonstrate that religious involvement favors health and longevity
across the life course. Examples include protective associations with stress,
depression, self-rated health, and infant birth weight. Theoretical and empirical
explanations for this relationship are offered, such as social and psychological
resources and healthy behaviors. The effects of religion on biological
functioning, including allostatic load and telomere length, are also discussed,
although this area is understudied. Considerations for the "dark-side" of
religious involvement are also offered. Suggestions for nurses wishing to protect
and promote the health of their patients using a holistic approach include
expanding knowledge of research on religion and health and advocating for
patients' spiritual needs by conducting a comprehensive spiritual assessment in
primary, secondary, and tertiary clinical settings.
PMID- 29957094
TI - Expanding Palliative Medicine across Care Settings: One Health System Experience.
AB - BACKGROUND: The success of our hospital-based Palliative Care program stimulated
requests to duplicate the program across the health system continuum of care.
OBJECTIVE: To develop a model of care focused on a high-need, high-cost
population that could be implemented across all care settings, including
hospitals and patients' homes. METHODS: To fiscally support program expansion
from hospital to home, we conducted a retrospective cost analysis for home-based
Palliative Care (HBPC)-enrolled patients with continuous claims months before
program enrollment through date of death. The HBPC enrollees were evaluated
against a cohort group of CMS (Centers for Medicare & Medicaid Service) and
Medicare Advantage patients who did not participate in the HBPC program (n =
3135). Twenty-one months of claims leading up to the date of death were evaluated
for both populations. The analysis was designed to test whether Palliative Care
patients demonstrated less overall claims expense and service utilization in the
same periods as patients without Palliative Care. Claim months were grouped into
three-month clusters for evaluation and statistical testing of per member per
month utilization and cost. RESULTS: Overall, HBPC patients demonstrated
significantly less service utilization and cost in the months leading up to
death. Cost differences were primarily driven by clear cost divergence in the
last three months of life [$9,843 (PC) vs. $27,530 (C)]. Our program grew from a
hospital-based program to include the establishment of a home-based program.
CONCLUSION: Palliative Care programs can successfully expand outside hospital
walls to serve a high need/high-cost patient population.
PMID- 29957096
TI - Patterns of Palliative Care Pharmacist Interventions and Outcomes as Part of
Inpatient Palliative Care Consult Service.
AB - INTRODUCTION: Palliative care uses a team approach, including physicians, nurses,
social workers, chaplains, and pharmacists. The pharmacist's role within
palliative care teams is increasing and initial favorable outcomes have been
reported. METHODS: This retrospective study evaluated adult hospitalized patients
seen by a part-time palliative care specialist pharmacist as part of the
palliative care consultation team at an academic health system during a 15-month
period between September 1, 2015, and March 30, 2017. Our study's objective is to
identify patterns of an inpatient palliative care pharmacist's interventions and
outcomes and evaluate the impact of pharmacist involvement on patient hospital
length of stay (LOS), length from admission to palliative care consult (LTC), and
time from consult to discharge or death (CTD). RESULTS: The palliative care
pharmacist was on service 35% of the time and saw 26.4% of the patient seen by
the palliative care team (n = 341 out of 1293). Each patient received an average
of 3.5 interventions with an average of 4.1 documented outcomes. The most common
interventions were optimizing palliative medication regimen and providing
education; most common outcomes were implementation of a change in palliative
medication regimen and education of healthcare professionals. Overall, patients
seen by the palliative care pharmacist were younger (p < 0.05), more likely to be
female (p < 0.05), and more likely to have a primary palliative consultation
reason listed as "pain" (p < 0.005). LOS, LTC, and CTD were significantly longer
for patients seen by palliative care pharmacist. CONCLUSION: Pharmacist
interventions and outcomes were predominantly related to optimizing symptoms by
changes in medication regimen and education of healthcare professionals. A
subanalysis of patients with known date of first pharmacist visit found
significantly improved LOS, LTC, and CTD for patients with early access to
palliative pharmacy (in addition to the other members of the palliative team)
compared to those without early access.
PMID- 29957095
TI - Concordance between Goals of Care and Treatment Decisions for Persons with
Dementia.
AB - BACKGROUND: Nursing home (NH) residents with dementia experience high rates of
intensive treatment near the end of life. Limited research examines whether
treatment is concordant with goals of care (GOC). OBJECTIVES: We analyzed data
from the GOC trial to describe family decision makers' preferred GOC and
perceptions of goal-concordant care for NH residents with late-stage dementia We
compared subsequent treatment orders when families chose a primary goal of
comfort versus other goals. DESIGN: We performed a secondary analysis of data
from baseline and 9-month family decision-maker interviews and chart reviews.
SETTING AND PARTICIPANTS: A total of 302 dyads of NH residents and family
decision makers in 22 North Carolina NHs were enrolled. MEASUREMENTS: In baseline
and follow-up interviews, families reported on their and NH staff's primary GOC,
and perceived prognosis and goal-concordant care. Chart reviews provided data on
treatment orders, hospital transfers, and hospice, which were compared after
selection of a primary goal of comfort versus other goals. RESULTS: Family chose
comfort as the primary goal for 66% of residents at baseline, and for nearly 80%
by 9 months or death. At baseline, 49% perceived concordance with NH staff on the
primary goal, and 69% at follow-up. In multivariate models, choice of comfort as
the primary goal, versus other goals, was associated with half as many hospital
transfers (0.11 vs. 0.25/90 person-days, confidence interval [-0.2 to -0.01]),
but not with hospice or treatment orders. CONCLUSIONS: Most families chose
comfort as the primary GOC. Further research is needed to translate this
preference into comfort-focused treatment plans for late-stage dementia.
Clinicaltrials.gov : NCT01565642 (3/26/12).
PMID- 29957097
TI - Life Program: Pilot Testing a Palliative Psychology Group Intervention.
AB - BACKGROUND: Psychosocial interventions for palliative care populations,
individuals with life-limiting illness, improve distress; however, less is known
about these interventions among military Veterans. OBJECTIVES: This quality
improvement project evaluated a palliative psychology group intervention to
reduce depression, anxiety, and stress among Veterans with advanced life-limiting
illness. METHODS: Veterans receiving palliative care at a mid-Atlantic VA
healthcare system were referred by a mental health provider. The group
intervention was delivered face-to-face in six to eight weekly sessions, with
groups of four to eight participants. The intervention (Life Program), was a
hybrid of cognitive-behavioral therapy and acceptance and commitment therapy that
targeted: personal values, mindfulness, and psychological flexibility. A single
arm pre-post-test design was used to assess depression, anxiety, and stress, and
satisfaction with the intervention. RESULTS: Seventy-five percent (39/52) of all
Veterans who were contacted expressed interest and agreed to participate.
Seventeen of 39 enrolled Veterans completed all sessions. The mean age of
participants who completed the program was 63.06 (standard deviation = 8.47).
Most participants were male (88%), Caucasian (58%), and had a cancer diagnosis
(65%). Mean pre-post reductions in depression (18.82 vs. 13.20), anxiety (16.59
vs. 14.59), stress (19.18 vs. 13.88), and psychological inflexibility were
observed. Mean differences in symptom severity were clinically meaningful.
Barriers to feasibility included transportation issues and illness burden.
CONCLUSIONS: Veterans who completed all sessions of a palliative psychology group
intervention had reductions in depression, anxiety, and stress. Estimates of the
treatment effects may be inflated using completer data alone. Further research is
needed to inform ways to improve program engagement and adherence and examine
efficacy in Veterans with advanced life-limiting illness.
PMID- 29957098
TI - The Role of Gender, Child Maltreatment, Alcohol Expectancies, and Personality
Pathology on Relationship Violence Among Undergraduates.
AB - Male ( n = 1,104) and female ( n = 1,337) college students' self-report surveys
on childhood maltreatment, alcohol expectancies, and narcissistic personality
traits are examined to determine their associations with relationship violence.
Intimate partner violence was measured using the violence subscales of the
revised Conflict Tactics. Because we were interested in the effects of gender and
because z tests of the correlations and t tests of means indicated men and women
differed significantly on several variables, ordinary least squares regression
models were run separately for men and women. Results suggest there are both
gender similarities and differences. Relationship violence was associated with
child sexual abuse for both men and women, whereas high scores on negative
alcohol expectancies and vulnerable narcissism, and low scores on grandiose
narcissism, were significantly associated with violence for men only. In
addition, z tests revealed the regression coefficients for child sexual abuse and
negative alcohol expectancies were significantly different for men and women.
Child sexual abuse and alcohol expectancies had stronger associations with men's
than women's violent behavior. In addition, the models explained a greater amount
of variance in men's than in women's behavior. Policy implications of the
research will be discussed.
PMID- 29957099
TI - Acute Effects of Dried Apple Consumption on Metabolic and Cognitive Responses in
Healthy Individuals.
AB - The objective of this study was to assess the potential of dried apple to
regulate acute blood glucose, insulin, satiety, and total plasma antioxidant
levels, and to explore the effect of dried apple on cognitive responses. Twenty
one healthy, normal-weight subjects completed the study which used a randomized
crossover design with repeated measures. After a fast of 10 h, a standardized
serving size of either dried apple or muffins was consumed. Blood glucose,
insulin, and antioxidant concentrations were measured at 0, 15, 30, 45, 60, 90,
and 120 min postprandial, and satiety was assessed every 15 min for 2 h.
Cognitive tests were administered before and 2 h after consumption of the test
food. The dried apple had significantly higher phenolic content and antioxidant
activities than the muffin (P <= .05). Consumption of the dried apples produced
significantly lower glucose concentrations at 30- (P <= .01; 95% CI [2.93
16.64]), 45- (P <= .02; 95% CI [2.41-17.88]), 60- (P <= .02; 95% CI [2.10
14.56]), and 120-min (P <= .01; 95% CI [8.16-16.80]) time points, and
significantly lower (P <= .03; 95% CI [0.60-8.70]) insulin concentrations at a 15
min time point than the muffins but offered little consistent differences in
antioxidant status, satiety, and cognitive function. These findings suggested
that the intake of dried apples could reduce postprandial blood glucose and
potentially increase the effectiveness of insulin responses in healthy
individuals but offered little consistent differences in antioxidant status,
satiety, and cognitive function.
PMID- 29957100
TI - Defining Provider-Prioritized Domains of Quality in Pediatric Home-Based Hospice
and Palliative Care: A Study of the Ohio Pediatric Palliative Care and End-of
Life Network.
AB - BACKGROUND: In 2017, the Ohio Pediatric Palliative Care and End-of-Life Network
(OPPEN) published nine domains of high-quality care for pediatric home-based
hospice and palliative care (HBHPC). Eight domains established by the National
Consensus Project (NCP) were validated for pediatric HBHPC, and a ninth domain of
"Continuity and Coordination of Care" was added. OBJECTIVE: The aim of this study
was to establish definition criteria for each of these domains. DESIGN AND
SETTING: Using a modified Delphi technique, providers from the OPPEN were
surveyed regarding definitions drawn from the NCP domain criteria. For the ninth
domain, new definition criteria were generated de novo based on qualitative
responses. RESULTS: Definition criteria were established for the nine domains of
quality in HBHPC previously identified. In the course of analysis, Bereavement
Care was established as a 10th domain of quality, and definition criteria
generated. CONCLUSIONS: This is the first study to define domains of quality for
pediatric HBHPC, and the second to leverage the infrastructure of a pediatric HPC
statewide consortium toward this work. Future studies are needed to establish
parent and patient-prioritized domains of quality in pediatric HBHPC, and to map
indicators validated in pediatrics to these domains.
PMID- 29957101
TI - Efficacy and Safety of Estradiol Valerate/Dienogest for the Management of Heavy
Menstrual Bleeding: A Multicenter, Double-Blind, Randomized, Placebo-Controlled,
Phase III Clinical Trial.
AB - BACKGROUND: To investigate the efficacy and safety of estradiol valerate
(EV)/dienogest (DNG) for the management of heavy menstrual bleeding (HMB) in
Asian and non-Asian women desiring contraception. MATERIALS AND METHODS: In this
multicenter, double-blind, phase III study, women were randomized 2:1 to receive
EV/DNG or placebo tablets daily for seven 28-day cycles. The primary endpoint was
the absolute change in menstrual blood loss (MBL) volume between the run-in and
efficacy phases (90 days each). Secondary endpoints included the proportion of
women with successful treatment (i.e., no episodes of MBL >=80 mL and a decrease
of <50% in MBL), percent change in MBL from the run-in phase, and change in
hemoglobin and serum ferritin levels. Adverse events (AEs) were monitored
throughout the study. RESULTS: Of the 341 women (mean age 34.7 +/- 7.7 years; 309
Asians, 32 non-Asians) randomized, 270 completed the study. Mean reduction in MBL
volume from run-in phase was significantly greater with EV/DNG than placebo
(366.75 mL vs. 149.14 mL; p < 0.0001), with ~52% and 12% of women, respectively,
experiencing successful treatment. Percent decrease in MBL volume from the run-in
phase was significantly greater with EV/DNG than placebo (63.5% vs. 24.8%; p <
0.0001). Hemoglobin and serum ferritin levels were increased with EV/DNG compared
with placebo. Study drug-related AEs were reported in 16.3% and 8.2% of women
with EV/DNG and placebo, respectively, none of which were of severe intensity.
CONCLUSIONS: EV/DNG may be a safe and effective option in the treatment of HMB in
Asian and non-Asian women who desire contraception.
PMID- 29957102
TI - Why Should Clinicians Be Concerned About Prescribing Compounded Hormones for
Menopausal Women?
PMID- 29957103
TI - Characterization of Clinical Vancomycin-Resistant Enterococcus faecium Isolated
in Eastern Hungary.
AB - OBJECTIVES: The aim of our study was to characterize and elicit the genetic
relatedness of emerging vancomycin-resistant enterococci (VRE) isolated between
2012 and 2015 at a teaching hospital in Debrecen, Hungary. RESULTS: Altogether 43
nonduplicate vancomycin-resistant Enterococcus faecium (VREfm) clinical isolates
were obtained. Matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry was used for species identification. Isolates showed 100% resistance
to ampicillin and ciprofloxacin while 81.4% were resistant to gentamicin. PCR
analysis revealed the presence of VanB in 40 and VanA in 3 isolates. Among ace,
agg, and esp virulence genes only esp was found in seven cases. Modified
microtiter-plate test showed 13 weak and 4 moderate biofilm producer isolates.
Pulsed-field gel electrophoresis revealed nine pulsotypes. According to
multilocus sequence typing all of the tested isolates belonged to clonal complex
17 (CC17). CONCLUSIONS: We report on the alarming emergence of multidrug
resistant VREfm belonging to CC17 at a tertiary hospital in Eastern Hungary. This
is the first report of sequence types 412 and 364 from this region. Although
outbreak did not occur the increasing prevalence of VREfm is of concern and
dissemination must be prevented with proper infection control measures and
regular VRE screening.
PMID- 29957104
TI - Pomegranate Juice Increases Sirtuin1 Protein in Peripheral Blood Mononuclear Cell
from Patients with Type 2 Diabetes: A Randomized Placebo Controlled Clinical
Trial.
AB - BACKGROUND: Few studies have examined anti-inflammatory effects of pomegranate
juice (PJ). The present study aimed to evaluate the effect of PJ on nuclear
factor kappa B (NF-kappaB) p65 and sirtuin1 in peripheral blood mononuclear cell
(PBMC), and plasma vascular inflammation biomarkers. METHODS: Patients with type
2 diabetes were randomly assigned to either the PJ (n = 22) or the placebo group
(n = 22). The patients in the PJ group received 250 mL of PJ daily for 12 weeks,
whereas the placebo group received corresponding control beverages of similar
color and energy content. At baseline and at the end of week 12, fasting plasma
concentrations of soluble intercellular adhesion molecule type 1 (sICAM-1),
soluble vascular cell adhesion molecule type 1 (sVCAM-1), and soluble E-selectin
(sE-selectin) were measured. NF-kappaB p65 and SIRT1 were measured in the PBMC.
RESULTS: Plasma sE-selectin concentration decreased significantly in the PJ group
at the end of week 12 compared to baseline (P < 0.001 for treatment effect), and
the reduction was significant in comparison with the placebo group (P < 0.05 for
treatment effect). There were no significant differences between the two groups
in plasma sICAM-1 and sVCAM-1. At the end of the study, compared with the placebo
group, NF-kappaB p65 in PBMC was significantly lower (P < 0.01 for treatment
effect) and SIRT1 was significantly higher (P < 0.0001 for treatment effect) in
the PJ group. CONCLUSION: This study supports the PJ consumption as a food with
potential benefits in individuals with type 2 diabetes as evidenced by
improvements in NF-kappaB and SIRT1 levels in PBMC of study participants.
PMID- 29957105
TI - Altered Gut Microbiota: A Link Between Diet and the Metabolic Syndrome.
AB - Diet with increased intake of energy-rich foods has long been implicated in the
etiology of metabolic syndrome. In recent years, an increasing body of evidence
has emerged that suggests that the intestinal microbial flora or "gut microbiota"
may play a crucial role in the development of metabolic syndrome and associated
disorders. Studies on animals and humans have shown that diet-induced changes in
gut microbiota may be causally involved in the pathogenesis of metabolic
syndrome. This article reviews the available evidence from studies on animal
models and humans with or without metabolic syndrome that have investigated the
impact of diet on intestinal microbial composition and activity on the metabolic
syndrome. The underlying mechanisms or pathways that link diet and altered gut
microbiota to the development of metabolic syndrome are discussed with special
emphasis on gut microbiota-induced changes in intestinal short-chain fatty acids,
metabolic endotoxemia, low-grade systemic inflammation, and innate immune system
activation and their inter-relationships to metabolic syndrome.
PMID- 29957106
TI - Depression and Prostate Cancer: Examining Comorbidity and Male-Specific Symptoms.
AB - Depression in men with prostate cancer is a significant and complex issue that
can challenge clinicians' diagnostic efforts. The objective of the current study
was to evaluate prototypic and male-specific depression symptoms and suicidal
ideation in men with a diagnosis of prostate cancer relative to those with and
without comorbidity. The Patient Health Questionnaire-9 (PHQ-9) and Male
Depression Risk Scale-22 (MDRS-22) were completed online along with demographic
and background variables by 100 men with a diagnosis of prostate cancer ( n = 54
prostatectomy, n = 33 receiving active treatment). Hierarchical logistic
regression was used to examine recent (past 2 weeks) suicide ideation. Over one
third of the sample (38%) reported a comorbidity, and this group had
significantly higher total depression scores on the PHQ-9 (Cohen's d = 0.65),
MDRS-22 emotion suppression ( d = 0.35), and drug use subscales ( d = 0.38)
compared to respondents without comorbidity. A total of 14% reported recent
suicidal ideation, of which 71.4% of cases were identified by the PHQ-9
"moderate" cut-off, and 85.7% of cases were identified by the MDRS-22 "elevated"
cut-off. After control variables, MDRS-22 subscales accounted for 45.1% of
variance in recent suicidal ideation. While limited by the exclusive use of self
report data, findings point to the potential benefits of evaluating male-specific
symptoms as part of depression and suicide risk screening in men with prostate
cancer and the need to be mindful of the heightened risk for depression among men
with prostate cancer who have comorbidity.
PMID- 29957107
TI - Estimating a Preference-Based Single Index Measuring the Quality-of-Life Impact
of Self-Management for Diabetes.
AB - OBJECTIVE: Self-management is becoming increasingly important in diabetes but is
neglected in conventional preference-based measures. The objective of this paper
was to generate health state utility values for a novel classification system
measuring the quality-of-life impact of self-management for diabetes, which can
be used to generate quality-adjusted life years (QALYs). METHODS: A large online
survey was conducted using a discrete choice experiment (DCE), with duration as
an additional attribute, on members of the UK general population ( n = 1,493) to
elicit values for health (social limitations, mood, vitality, hypoglycaemia) and
non-health (stress, hassle, control, support) aspects of self-management in
diabetes. The data were modelled using a conditional fixed-effects logit model
and utility estimates were anchored on the one to zero (full health to dead)
scale. RESULTS: The model produced significant and consistent coefficients, with
one logical inconsistency and 3 insignificant coefficients for the milder levels
of some attributes. The anchored utilities ranged from 1 for the best state to
0.029 for the worst state (meaning worse than dead) defined by the classification
system. CONCLUSION: The results presented here can potentially be used to
generate utility values capturing the day to day impact of interventions in
diabetes on both health and self-management. These utility values can potentially
be used to generate QALYs for economic models of the cost-effectiveness of
interventions in diabetes.
PMID- 29957108
TI - Letter to the Editor. Cafeteria approach to management of trigeminal neuralgia:
stereotactic radiosurgery as a preferred option.
PMID- 29957109
TI - A sustained systemic inflammatory response syndrome is associated with shunt
dependent hydrocephalus after aneurysmal subarachnoid hemorrhage.
AB - OBJECTIVE The authors sought to evaluate whether a sustained systemic
inflammatory response was associated with shunt-dependent hydrocephalus following
aneurysmal subarachnoid hemorrhage. METHODS A retrospective analysis of 193
consecutive patients with aneurysmal subarachnoid hemorrhage was performed.
Management of hydrocephalus followed a stepwise algorithm to determine the need
for external CSF drainage and subsequent shunt placement. Systemic inflammatory
response syndrome (SIRS) data were collected for all patients during the first 7
days of hospitalization. Patients who met the SIRS criteria every day for the
first 7 days of hospitalization were considered as having a sustained SIRS.
Univariate and multivariate regression analyses were used to determine predictors
of shunt dependence. RESULTS Sixteen percent of patients required shunt
placement. Sustained SIRS was observed in 35% of shunt-dependent patients
compared to 14% in non-shunt-dependent patients (p = 0.004). On multivariate
logistic regression, female sex (OR 0.35, 95% CI 0.142-0.885), moderate to severe
vasospasm (OR 3.78, 95% CI 1.333-10.745), acute hydrocephalus (OR 21.39, 95% CI
2.260-202.417), and sustained SIRS (OR 2.94, 95% CI 1.125-7.689) were
significantly associated with shunt dependence after aneurysmal subarachnoid
hemorrhage. Receiver operating characteristic analysis revealed an area under the
curve of 0.83 for the final regression model. CONCLUSIONS Sustained SIRS was a
predictor of shunt-dependent hydrocephalus following aneurysmal subarachnoid
hemorrhage even after adjustment for potential confounding variables in a
multivariate logistic regression model.
PMID- 29957110
TI - The oculomotor-tentorial triangle. Part 2: a microsurgical workspace for vascular
lesions in the crural and ambient cisterns.
AB - OBJECTIVE Pathology in the region of the basilar quadrifurcation, anterolateral
midbrain, medial tentorium, and interpeduncular and ambient cisterns may be
accessed anteriorly via an orbitozygomatic (OZ) craniotomy. In Part 1 of this
series, the authors explored the anatomy of the oculomotor-tentorial triangle
(OTT). In Part 2, the versatility of the OTT as a surgical workspace for treating
vascular pathology is demonstrated. METHODS Sixty patients with 61 vascular
pathologies treated within or via the OTT from 1998 to 2017 by the senior author
were retrospectively reviewed. Patients were grouped together based on
pathology/surgical procedure and included 1) aneurysms (n = 19); 2) posterior
cerebral artery (PCA)/superior cerebellar artery (SCA) bypasses (n = 24); 3)
brainstem cavernous malformations (CMs; n = 14); and 4) tentorial region dural
arteriovenous fistulas (dAVFs; n = 4). The majority of patients were approached
via an OZ craniotomy, wide sylvian fissure split, and temporal lobe mobilization
to widen the OTT. RESULTS Aneurysm locations included the P1-P2 junction (n = 7),
P2A segment (n = 9), P2/3 (n = 2), and basilar quadrification (n = 1). Aneurysm
treatments included clip reconstruction (n = 12), wrapping (n = 3), proximal
occlusion (n = 2), and trapping with (n = 1) or without (n = 1) bypass.
Pathologies in the bypass group included vertebrobasilar insufficiency (VBI; n =
3) and aneurysms of the basilar trunk (n = 13), basilar apex (n = 4), P1 PCA (n =
2), and s1 SCA (n = 2). Bypasses included M2 middle cerebral artery (MCA)-radial
artery graft (RAG)-P2 PCA (n = 8), M2 MCA-saphenous vein graft (SVG)-P2 PCA (n =
3), superficial temporal artery (STA)-P2 PCA (n = 5) or STA-s1 SCA (n = 3), s1
SCA-P2 PCA (n = 1), V3 vertebral artery (VA)-RAG-s1 SCA (n = 1), V3 VA-SVG-P2 PCA
(n = 1), anterior temporal artery-s1 SCA (n = 1), and external carotid artery
(ECA)-SVG-s1 SCA (n = 1). CMs were located in the midbrain (n = 10) or
pontomesencephalic junction (n = 4). dAVFs drained into the tentorial, superior
petrosal, cavernous, and sphenobasal sinuses. High rates of aneurysm occlusion
(79%), bypass patency (100%), complete CM resection (86%), and dAVF obliteration
(100%) were obtained. The overall rate of permanent oculomotor nerve palsy was
8.3%. The majority of patients in the aneurysm (94%), CM (93%), and dAVF (100%)
groups had stable or improved modified Rankin Scale scores. CONCLUSIONS The OTT
is an important anatomical triangle and surgical workspace for vascular lesions
in and around the crural and ambient cisterns. The OTT can be used to approach a
wide variety of vascular pathologies in the region of the basilar quadrifurcation
and anterolateral midbrain.
PMID- 29957111
TI - The oculomotor-tentorial triangle. Part 1: microsurgical anatomy and techniques
to enhance exposure.
AB - OBJECTIVE Access to the ventrolateral pontomesencephalic area may be required for
resecting cavernous malformations, performing revascularization of the upper
posterior circulation, and treating vascular lesions such as aneurysms. However,
such access is challenging because of nearby eloquent structures. Commonly used
corridors to this surgical area include the optico-carotid, supracarotid, and
carotid-oculomotor triangles. However, the window lateral to the oculomotor nerve
can also be used and has not been studied. The authors describe the anatomical
window formed between the oculomotor nerve and the medial tentorial edge (the
oculomotor-tentorial triangle [OTT]) to the ventrolateral pontomesencephalic
area, and assess techniques to expand it. METHODS Four cadaveric heads (8 sides)
underwent orbitozygomatic craniotomy. The OTT was exposed via a pretemporal
approach. The contents of the OTT were determined and their anatomical features
were recorded. Also, dimensions of the brainstem surface exposed lateral and
inferior to the oculomotor nerve were measured. Measurements were repeated after
completing a transcavernous approach (TcA), and after resection of temporal lobe
uncus (UnR). RESULTS The s1 segment and proximal s2 segment of the superior
cerebellar artery (SCA) and P2A segment of the posterior cerebral artery (PCA)
were the main contents of the OTT, with average exposed lengths of 6.4 +/- 1.3 mm
and 5.5 +/- 1.6 mm for the SCA and PCA, respectively. The exposed length of the
SCA increased to 9.6 +/- 2.7 mm after TcA (p = 0.002), and reached 11.6 +/- 2.4
mm following UnR (p = 0.004). The exposed PCA length increased to 6.2 +/- 1.6 mm
after TcA (p = 0.04), and reached 10.4 +/- 1.8 mm following UnR (p < 0.001). The
brainstem surface was exposed 7.1 +/- 0.5 mm inferior and 5.6 +/- 0.9 mm lateral
to the oculomotor nerve initially. The exposure inferior to the oculomotor nerve
increased to 9.3 +/- 1.7 mm after TcA (p = 0.003), and to 9.9 +/- 2.5 mm after
UnR (p = 0.21). The exposure lateral to the oculomotor nerve increased to 8.0 +/-
1.7 mm after TcA (p = 0.001), and to 10.4 +/- 2.4 mm after UnR (p = 0.002).
CONCLUSIONS The OTT is an anatomical window that provides generous access to the
upper ventrolateral pontomesencephalic area, s1- and s2-SCA, and P2A-PCA. This
window may be efficiently used to address various pathologies in the region and
is considerably expandable by TcA and/or UnR.
PMID- 29957112
TI - Flow diversion and microvascular plug occlusion for the treatment of a complex
unruptured basilar/superior cerebellar artery aneurysm: case report.
AB - The authors present the unusual case of a complex unruptured basilar artery
terminus (BAT) aneurysm in a 42-year-old symptomatic female patient presenting
with symptoms of mass effect. Due to the fusiform incorporation of both the BAT
and left superior cerebellar artery (SCA) origin, simple surgical or endovascular
treatment options were not feasible in this case. A 2-staged (combined
deconstructive/reconstructive) procedure was successfully performed: first
occluding the left SCA with a Pipeline embolization device (PED) coupled to a
microvascular plug (MVP) in the absence of antiplatelet coverage, followed by
reconstruction of the BAT by deploying a second PED from the right SCA into the
basilar trunk. Six-month follow-up angiography confirmed uneventful aneurysm
occlusion. The patient recovered well from her neurological symptoms. This case
report illustrates the successful use of a combined staged
deconstructive/reconstructive endovascular approach utilizing 2 endoluminal
tools, PED and MVP, to reconstruct the BAT and occlude a complex aneurysm.
PMID- 29957113
TI - Possible involvement of pericytes in intraplaque hemorrhage of carotid artery
stenosis.
AB - OBJECTIVE Intraplaque hemorrhage (IPH) is most often caused by the rupture of
neovessels; however, the factors of intraplaque neovessel vulnerability remain
unclear. In this study, the authors focused on pericytes and aimed to investigate
the relationship between IPH and pericytes. METHODS The authors retrospectively
analyzed the medical records of all patients with carotid artery stenoses who had
undergone carotid endarterectomy at their hospitals between August 2008 and March
2016. Patients with carotid plaques that could be evaluated histopathologically
were eligible for study inclusion. Intraplaque hemorrhage was analyzed using
glycophorin A staining, and patients were divided into the following 2 groups
based on the extent of granular staining: high IPH (positive staining area > 10%)
and low IPH (positive staining area <= 10%). In addition, intraplaque neovessels
were immunohistochemically evaluated using antibodies to CD34 as an endothelial
cell marker or antibodies to NG2 and CD146 as pericyte markers. The relationship
between IPH and pathology for intraplaque neovessels was investigated. RESULTS
Seventy of 126 consecutive carotid stenoses were excluded due to the lack of a
specimen for histopathological evaluation; therefore, 53 patients with 56 carotid
artery stenoses were eligible for study inclusion. Among the 56 stenoses, 37
lesions had high IPH and 19 had low IPH. The number of CD34-positive neovessels
was equivalent between the two groups. However, the densities of NG2- and CD146
positive neovessels were significantly lower in the high IPH group than in the
low IPH group (5.7 +/- 0.5 vs. 17.1 +/- 2.4, p < 0.0001; 6.6 +/- 0.8 vs. 18.4 +/-
2.5, p < 0.0001, respectively). CONCLUSIONS Plaques with high IPH are associated
with fewer pericytes in the intraplaque neovessels. This finding may help in the
development of novel therapeutic strategies targeting pericytes.
PMID- 29957114
TI - Letter to the Editor. Transcranial MRgFUS for movement disorder: toward a wider
and affordable employment for functional neurosurgery through 1.5-T MRI?
PMID- 29957115
TI - A football helmet prototype that reduces linear and rotational acceleration with
the addition of an outer shell.
AB - OBJECTIVE Amid the public health controversy surrounding American football, a
helmet that can reduce linear and rotational acceleration has the potential to
decrease forces transmitted to the brain. The authors hypothesized that a
football helmet with an outer shell would reduce both linear and rotational
acceleration. The authors' objectives were to 1) determine an optimal material
for a shock-absorbing outer shell and 2) examine the ability of an outer shell to
reduce linear and/or rotational acceleration. METHODS A laboratory-based
investigation was undertaken using an extra-large Riddell Revolution football
helmet. Two materials (Dow Corning Dilatant Compound and Sorbothane) were
selected for their non-Newtonian properties (changes in viscosity with shear
stress) to develop an outer shell. External pads were attached securely to the
helmet at 3 locations: the front boss, the side, and the back. The helmet was
impacted 5 times per location at 6 m/sec with pneumatic ram testing. Two-sample t
tests were used to evaluate linear/rotational acceleration differences between a
helmet with and a helmet without the outer shell. RESULTS Sorbothane was superior
to the Dow Corning compound in force reduction and recovered from impact without
permanent deformation. Of 5 different grades, 70-duro (a unit of hardness
measured with a durometer) Sorbothane was found to have the greatest energy
dissipation and stiffness, and it was chosen as the optimal outer-shell material.
The helmet prototype with the outer shell reduced linear acceleration by 5.8%
(from 75.4 g to 71.1 g; p < 0.001) and 10.8% (from 89.5 g to 79.8 g; p = 0.033)
at the side and front boss locations, respectively, and reduced rotational
acceleration by 49.8% (from 9312.8 rad/sec2 to 4671.7 rad/sed2; p < 0.001) at the
front boss location. CONCLUSIONS Sorbothane (70 duro) was chosen as the optimal
outer-shell material. In the outer-shell prototype helmet, the results
demonstrated a 5%-10% reduction in linear acceleration at the side and front boss
locations, and a 50% reduction in rotational acceleration at the front boss
location. Given the paucity of publicly reported helmet-design literature and the
importance of rotational acceleration in head injuries, the substantial reduction
seen in rotational acceleration with this outer-shell prototype holds the
potential for future helmet-design improvements.
PMID- 29957116
TI - Epidemiology of ruptured brain arteriovenous malformation: a National Cohort
Study in Korea.
AB - OBJECTIVE Brain arteriovenous malformation (BAVM) is a rare cerebrovascular
disease that causes intracranial hemorrhage. Although several reports have
demonstrated the epidemiological features of BAVM in Western countries, no
epidemiological investigations regarding BAVM have been reported in Korea. The
authors aimed to investigate the national epidemiology of ruptured BAVM in a
Korean population. METHODS The authors used data from the National Health
Insurance Service-National Sample Cohort (NHIS-NSC). The original cohort included
approximately 1 million individuals (2% of the Korean population) with 12-year
claim data (2002-2013). To construct an initial cohort for investigation, the
authors selected 1,016,820 registered individuals in 2005. Subjects with a
history of cerebrovascular disease (code I6xx) and BAVM (Q282) between 2002 and
2004 were washed-out to identify incident cases. During the 9-year follow-up
(2005-2013), the incidence of BAVM was calculated using the earliest date of
diagnosis of ruptured or unruptured BAVM. Direct standardization was applied to
the crude incidence. Mortality and disability were evaluated using registration
data. Related diagnostic procedures were also analyzed. RESULTS A total of
8,802,696 person-years of observation were noted. During observation, 308
patients were diagnosed with a ruptured BAVM. The crude incidence of ruptured
BAVM was 3.5 per 100,000 person-years. There was no sex difference in incidence.
The mortality rate for patients with a ruptured BAVM 1 month after diagnosis was
12.7%. At 1-year and 5-year follow-up examinations, mortality rates were 17.2%
and 22.1%, respectively. Severe disability-free survival rates of patients with
ruptured AVMs were 75.3% and 69.8% at 1-year and 5-year follow-up, respectively.
CONCLUSIONS The standardized incidence of ruptured BAVMs was 3.6 per 100,000
person-years in Korea. Ruptured BAVMs resulted in high mortality and disability
rates.
PMID- 29957117
TI - Letter to the Editor. Is the serum glucose/potassium ratio a reliable prognostic
factor for aneurysmal SAH?
PMID- 29957118
TI - Antimicrobial Peptides: Features, Action, and Their Resistance Mechanisms in
Bacteria.
AB - In recent years, because of increased resistance to conventional antimicrobials,
many researchers have started to study the synthesis of new antibiotics to
control the disease-causing effects of infectious pathogens. Antimicrobial
peptides (AMPs) are among the newest antibiotics; these peptides are integral
compounds in all kinds of organisms and play a significant role in microbial
ecology, and critically contribute to the innate immunity of organisms by
destroying invading microorganisms. Moreover, AMPs may encourage cells to produce
chemokines, stimulate angiogenesis, accelerate wound healing, and influence
programmed cell death in multicellular organisms. Bacteria differ in their
inherent susceptibility and resistance mechanisms to these peptides when
responding to the antimicrobial effects of AMPs. Generally, the development of
AMP resistance mechanisms is driven by direct competition between bacterial
species, and host and pathogen interactions. Several studies have shown diverse
mechanisms of bacterial resistance to AMPs, for example, some bacteria produce
proteases and trapping proteins; some modify cell surface charge, change membrane
fluidity, and activate efflux pumps; and some species make use of biofilms and
exopolymers, and develop sensing systems by selective gene expression. A closer
understanding of bacterial resistance mechanisms may help in developing novel
therapeutic approaches for the treatment of infections caused by pathogenic
organisms that are successful in developing extensive resistance to AMPs. Based
on these observations, this review discusses the properties of AMPs, their
targeting mechanisms, and bacterial resistance mechanisms against AMPs.
PMID- 29957119
TI - Laparoscopic Excision of an Obstructing Soave Cuff in Hirschsprung's Disease.
AB - BACKGROUND: The Soave pull-through for Hirschsprung's disease leaves a muscular
cuff of aganglionosis surrounding the pull-through. In some patients, this cuff
can extrinsically compress the pull-through, leading to chronic enterocolitis and
failure to thrive. We describe a novel technique for managing the Soave cuff as
an alternative to a complete redo pull-through. PROCEDURE: A laparoscopic
excision of the intraperitoneal portion of the Soave cuff is performed, taking
care to avoid injury to bladder, vas deferens, or vagina. The extraperitoneal
portion of the cuff, adjacent to the bladder/vagina, is left in place. The
excision is tailored to eliminate the obstruction and minimize injury to
surrounding structures. Diverting colostomy is not necessary and patients are
discharged the next day. RESULTS: Three patients successfully underwent excision
without any operative complications and without the need for a colostomy. They
had resolution of their chronic enterocolitis. CONCLUSION: In patients with an
obstructing Soave cuff, a laparoscopic excision should be considered as a
surgical option. We found that the procedure can be effective, with little
morbidity.
PMID- 29957120
TI - Folate conjugated vs PEGylated phytosomal casein nanocarriers for codelivery of
fungal- and herbal-derived anticancer drugs.
AB - AIM: Monascin and ankaflavin, the major fractions of the fungal-derived monascus
yellow pigments, were incorporated with the herbal drug, resveratrol (RSV) within
the core of folate-conjugated casein micelles (FA-CAS MCs, F1) for active
targeting. PEGylated RSV-phospholipid complex bilayer enveloping casein-loaded
micelles (PEGPC-CAS MCs) were also developed as passive-targeted nanosystem.
RESULTS: FA- and PEGPC-CAS MCs demonstrated a proper size with monomodal
distribution, sustained drug release profiles and good hemocompatibility. The
coloaded MCs showed superior cytotoxicity to MCF-7 breast cancer cells compared
with free drugs. Both nanosystems exerted excellent in vivo antitumor efficacy in
breast cancer bearing mice with PEGylated MCs showing comparable tumor regression
to folate-conjugated MCs. CONCLUSION: Evergreen nanoplatforms coloaded with
monascus yellow pigments and RSV were effective for breast cancer treatment.
PMID- 29957121
TI - Sesame Oil and an Aqueous Extract Derived from Sesame Oil Enhance Regression of
Preexisting Atherosclerotic Lesions in Low-Density Lipoprotein Receptor Knockout
Mice.
AB - Diet and exercise are recommended both as a prophylactic and as a therapeutic
approach for patients with established coronary artery disease. We previously
reported that sesame oil (SESO) and its aqueous extract (SOAE) showed
antiatherosclerotic and anti-inflammatory properties. We also observed that genes
involved in reverse cholesterol transport (RCT) might be activated. In this
study, we tested whether post-treatment with SESO or SOAE would reduce
preexisting atherosclerosis by enhancing RCT. Female low-density lipoprotein
receptor knockout (LDL-R-/-) mice were fed an atherogenic diet for 3 months,
followed by post-treatment with either control or SESO or SOAE for 1 month.
Plasma lipids and atherosclerotic lesions were quantified at the end of the
study. RNA was extracted from the aortic tissues and used for real-time
polymerase chain reaction analysis. SESO and SOAE post-treatment significantly
reduced atherosclerotic lesions in LDL-R-/- mice compared to controls. No
significant change in plasma cholesterol, triglyceride, or LDL cholesterol levels
was observed. Aortic gene analysis showed that the SESO/SOAE post-treatment
reduced inflammatory gene expression and induced genes involved in cholesterol
metabolism and RCT. This is the first study that demonstrates that post-treatment
with SESO and SOAE could be an effective treatment for preexisting
atherosclerosis and inflammation. The study also may suggest that reducing
inflammation might be conducive to an accelerated regression of lesions.
PMID- 29957122
TI - Peripheral Lymphocytes, Obesity, and Metabolic Syndrome in Young Adults: An
Immunometabolism Study.
AB - BACKGROUND: Obesity is characterized by a low-intensity chronic inflammatory
process in which immune system cells interact in a complex network, which affects
systemic metabolic processes. This raises interest in analyzing possible changes
in the proportions of immune system cells in individuals with obesity with and
without metabolic syndrome (MS), in relation to their body composition. METHODS:
Circulating cells were analyzed with flow cytometry in young adults: monocytes,
granulocytes, lymphocytes (T, B, and natural killer [NK]), TCD4+CD62-, TCD8+CD28
, and naive and memory cells of TCD3+ and TCD4+. Body composition was obtained by
bioelectrical impedance analysis and dual-energy X-ray absorptiometry, and
metabolic parameters. RESULTS: A total of 169 persons were evaluated: 20%
presented normal body mass index (BMI); 49% was overweight, and 31% had obesity;
28% had MS. It was observed that with an increase in BMI and visceral adipose
tissue increase (VATI), body composition and biochemical variables were
negatively altered. With regard to cell subpopulations, total lymphocytes
increased and granulocytes and NK lymphocytes decreased in patients with MS and
VATI. Memory cells increased with BMI and VATI. In individuals with MS,
monocytes, and NK lymphocytes comprised a negative association with VAT, fat
mass, and skeletal muscle mass (SMM). In individuals with MS and VATI, a negative
correlation was observed between monocytes and SMM. CONCLUSIONS: Significant
changes were detected in the subpopulations of lymphocytes, suggesting that
weight gain, SMM, and VAT accumulation gave rise to immunological changes at the
peripheral level, and the presence of increased memory cells could be related to
low-intensity chronic inflammation.
PMID- 29957123
TI - Pediatric Heart Transplantation Long-Term Survival in Different Age and
Diagnostic Groups: Analysis of a National Database.
AB - BACKGROUND: The purpose of this study was to evaluate differences in long-term
survival without the influence of early mortality, and to identify factors
associated with one-year conditional ten-year survival after heart
transplantation (HTx) across different age and diagnostic groups. METHODS: Organ
Procurement and Transplant Network data from January 1990 to December 2005 were
used. Cohort was divided according to age (infants [<1 year], children [>1-10
years], and adolescents [11-18 years]) and diagnosis (cardiomyopathy and
congenital heart disease [CHD]). Factors associated with one-year conditional ten
year survival were identified using multivariable logistic regression and using a
case-control design. RESULTS: One-year conditional ten-year survivors included
1,790 patients compared to 1,114 patients who died after the first posttransplant
year and within ten years of transplant with a median follow-up of 4.8 years.
Predictors of one-year conditional ten-year survival for infants were recipient's
Caucasian race (odds ratio [OR]: 1.9, 95% confidence interval [CI]: 1.3-2.7) and
donor-recipient weight ratio (OR: 0.8, 95% CI: 0.6-1); for children: Caucasian
race (OR: 1.6, 95% CI: 1.2-2.1), retransplantation (OR: 0.4, 95% CI: 0.2-0.6),
and transplantation after the year 2000 (OR: 1.5, 95% CI: 1.1-2.1); for
adolescents only Caucasian race (OR: 2.5, 95% CI: 1.9-2.3). In both CHD and
cardiomyopathy, adolescents had worse survival compared to infants and children.
There was an era effect with improved survival after 2000. Male gender was a
predictor of survival in cardiomyopathy group. CONCLUSION: Predictors of one-year
conditional ten-year survival varied among groups. These data and analyses
provide important information that may be useful to clinicians, particularly when
counseling patients and families regarding expectations of survival after
pediatric HTx.
PMID- 29957124
TI - Racial/Ethnic and Socioeconomic Disparities in Total Knee Arthroplasty 30- and 90
Day Readmissions: A Multi-Payer and Multistate Analysis, 2007-2014.
AB - Previous studies have addressed racial/ethnic and socioeconomic disparities in
total knee arthroplasty (TKA) within the Medicare population. However, there is
limited research examining these disparities across racial/ethnic and
socioeconomic groups in the general population. This study used administrative
data from the State Inpatient Databases from the Healthcare Cost and Utilization
Project for the years 2007-2014 from California (2007-2011 only), Florida, New
York, and Maryland (2012-2014 only). In all, 739,857 TKA readmission-eligible
patients aged >=8 years were included in the analysis. Black patients and
patients with Medicaid had a higher likelihood of 30- and 90-day readmissions
compared to white patients and patients with private insurance, respectively.
Patients living in higher median income areas and patients treated at higher
volume hospitals had lower likelihoods of 30- and 90-day readmissions compared to
patients in the lowest median income quartile and patients treated at the lowest
volume hospitals, respectively. These results confirmed racial/ethnic and
socioeconomic disparities in TKA readmissions across 4 geographically diverse
states, identified public insurance status as the salient factor across
subpopulations, and raise awareness of the existence of these disparities outside
of the Medicare population.
PMID- 29957125
TI - Role of androgens in energy metabolism affecting on body composition, metabolic
syndrome, type 2 diabetes, cardiovascular disease, and longevity: lessons from a
meta-analysis and rodent studies.
AB - Testosterone is a sex hormone produced by testicular Leydig cells in males. Blood
testosterone concentrations increase at three time-periods in male life-fetal,
neonatal (which can be separated into newborn and infant periods), and pubertal
stages. After peaking in the early 20s, the blood bioactive testosterone level
declines by 1-2% each year. It is increasingly apparent that a low testosterone
level impairs general physical and mental health in men. Here, this review
summarizes recent systematic reviews and meta-analyses of epidemiological studies
in males (including cross-sectional, longitudinal, and androgen deprivation
studies, and randomized controlled testosterone replacement trials) in relation
to testosterone and obesity, body composition, metabolic syndrome, type 2
diabetes, cardiovascular disease, and longevity. Furthermore, underlying
mechanisms are discussed using data from rodent studies involving castration or
androgen receptor knockout. This review provides an update understanding of the
role of testosterone in energy metabolism. Abbreviations AR: androgen receptor;
CV: cardiovascular; FDA: US Food and Drug Administration; HFD: high-fat diet; KO:
knockout; MetS: metabolic syndrome; RCT: randomized controlled trial; SHBG: sex
hormone binding globulin; SRMA: systematic review and meta-analysis; TRT:
testosterone replacement therapy; T2DM:type 2 diabetes mellitus.
PMID- 29957126
TI - Establishing a local coalition for addressing social determinants of hypertension
in Quibdo (Colombia): a description and reflection on the process.
AB - One-fourth of the adult population of Colombia is estimated to have hypertension.
However, there has been relatively little attention to participatory approaches
that address the social determinants of hypertension at the local level in
Colombia. Early stages of a coalition for addressing hypertension in Quibdo
(Colombia) included a stakeholder analysis and engagement of local organizations.
This was followed by defining mutual goals, agreement of rules for decision
making, and refining a shared vision. Based on a unified understanding of factors
influencing hypertension risk, 12 organizations joined the local coalition. They
developed an action plan for preventing hypertension and eliminating social
disparities in its distribution. Lessons learned during this process suggest
that, in marginalized urban areas of middle- and low-income countries, particular
attention should be paid, at early implementation stages of coalition, to context
specific challenges and opportunities, coalition membership and structure,
reframing health, and strengthening capacity.
PMID- 29957127
TI - Health Care System Factors Associated with Transition Preparation in Youth with
Special Health Care Needs.
AB - The aim of this study was to assess: (1) the proportion of youth with special
health care needs (YSHCN) with adequate transition preparation, (2) whether
transition preparation differs by individual, condition-related and health care
system-related factors, and (3) whether specific components of the medical home
are associated with adequate transition preparation. The authors conducted a
cross-sectional analysis of the 2009-2010 National Survey of Children with
Special Health Care Needs, which surveyed a nationally representative sample of
17,114 parents of YSHCN ages 12 to 18 years. Adequate transition preparation was
based on positive responses to questions about transition to an adult provider,
changing health care needs, maintaining insurance coverage, and if providers
encouraged YSHCN to take responsibility for health care needs. Weighted
descriptive, bivariate and multivariate analyses were conducted to determine the
association between patient and health care system factors and adequate
transition preparation. Overall, 32.1% of YSHCN had adequate transition
preparation. Older age, female sex, income <=400% of the poverty level, lack of
medical complexity, and having shared decision making, family-centered care, and
effective care coordination were associated with increased odds of transition
preparation. The majority of YSHCN do not receive adequate transition preparation
and younger, male adolescents with medical complexity were less likely to receive
transition preparation. Different patterns of disparities were identified for
each subcomponent measure of transition preparation, which may help target at
risk populations for specific services. Efforts to improve transition preparation
should leverage specific components of the medical home including care
coordination, shared decision making, and family-centered care.
PMID- 29957128
TI - Prevalence and Characteristics of Sequence Type 131 Escherichia coli Isolated
from Children with Bacteremia in 2000-2015.
AB - Escherichia coli sequence type (ST) 131 has emerged as a higher virulent and
multidrug-resistant pathogen worldwide. This study aimed to identify the
prevalence and characteristics of E. coli ST131 isolated from Korean children
with bacteremia at a single center for 16 years. We retrospectively reviewed
culture-proven E. coli bacteremia cases of children aged <=18 years between 2000
and 2015. E. coli isolates were analyzed using multilocus sequence typing, fimH
typing, and CTX-M typing. Among 177 children with E. coli bacteremia, a total of
21 (11.9%) ST131 isolates and 37 (20.9%) extended spectrum beta-lactamase (ESBL)
producing E. coli were identified. Nineteen (90.5%) isolates of ST131 E. coli had
the fimH gene, of which three were assigned to subclone H30. There was a
significant difference in prevalence of ESBL production between ST131 (n = 8,
38.1%) and non-ST131 (n = 29, 18.6%) isolates (p = 0.039). Five ESBL-producing
ST131 E. coli isolates had the blaCTX-M gene: two carried blaCTX-M-14, two
carried blaCTX-M-15, and one carried both blaCTX-M-14 and blaCTX-M-15. ST131
isolates had higher resistance rates to piperacillin/tazobactam (38.5% vs.
10.0%), cefotaxime (38.1% vs. 16.7%), amikacin (23.8% vs. 1.9%), and gentamicin
(52.4% vs. 28.8%) than non-ST131 isolates (p < 0.05, for all). There were no
significant differences in the rate of shock and mortality between patients
infected with ST131 (16.7% and 5.6%) and non-ST131 isolates (24.2% and 9.8%).
Prevalence of ST131 E. coli causing bacteremia in children was not different from
that in adults or that causing urinary tract infection in children in Korea.
However, because ST131 clones are more likely to be ESBL producing and more
resistant to empirical antibiotics used in sepsis than are non-ST131 clones,
surveillance for the prevalence of ST131 and its drug resistance should be
continued.
PMID- 29957129
TI - Switchable Adhesion Actuator for Amphibious Climbing Soft Robot.
AB - Climbing soft robots are of tremendous interest in both science and engineering
due to their potential applications in intelligent surveillance, inspection,
maintenance, and detection under environments away from the ground. The challenge
lies in the design of a fast, robust, switchable adhesion actuator to easily
attach and detach the vertical surfaces. Here, we propose a new design of
pneumatic-actuated bioinspired soft adhesion actuator working both on ground and
under water. It is composed of extremely soft bilayer structures with an embedded
spiral pneumatic channel resting on top of a base layer with a cavity. Rather
than the traditional way of directly pumping air out of the cavity for suction in
hard polymer-based adhesion actuator, we inflate air into the top spiral channel
to deform into a stable 3D dome shape for achieving negative pressure in the
cavity. The characterization of the maximum shear adhesion force of the proposed
soft adhesion actuator shows strong and rapid reversible adhesion on multiple
types of smooth and semi-smooth surfaces. Based on the switchable adhesion
actuator, we design and fabricate a novel load-carrying amphibious climbing soft
robot (ACSR) by combining with a soft bending actuator. We demonstrate that it
can operate on a wide range of foreign horizontal and vertical surfaces including
dry, wet, slippery, smooth, and semi-smooth ones on ground and also under water
with certain load-carrying capability. We show that the vertical climbing speed
can reach about 286 mm/min (1.6 body length/min) while carrying over 200 g object
(over 5 times the weight of ACSR itself) during climbing on ground and under
water. This research could largely push the boundaries of soft robot capabilities
and multifunctionality in window cleaning and underwater inspection under harsh
environment.
PMID- 29957130
TI - Cuff Pressure Algometry in Patients with Chronic Pain as Guidance for
Circumferential Tissue Compression for Wearable Soft Exoskeletons: A Systematic
Review.
AB - In this article, we report on a systematic review of the literature on pressure
pain thresholds induced and assessed by computerized cuff pressure algometry
(CPA). The motivation for this review is to provide design guidance on pressure
levels for wearable soft exoskeletons and similar wearable robotics devices. In
our review, we focus on CPA studies of patients who are candidates for wearable
soft exoskeletons, as pain-related physiological mechanisms reportedly differ
significantly between healthy subjects and patients with chronic pain. The
results indicate that circumferential limb compression in patients most likely
becomes painful at ~10-18 kPa and can become unbearable even below 25 kPa. The
corresponding ranges for healthy control subjects are 20-42 kPa (painful limits)
and 34-84 kPa (unbearable levels). In addition, the increase of pain with time
tends to be significantly higher, and the adaptation to pain significantly lower,
than in healthy subjects. The results of this review provide guidance to
designers of wearable robotics for populations with chronic pain regarding rates
and magnitudes of tissue compression that may be unacceptable to users.
PMID- 29957131
TI - Soft Biomimetic Fish Robot Made of Dielectric Elastomer Actuators.
AB - This article presents the design, fabrication, and characterization of a soft
biomimetic robotic fish based on dielectric elastomer actuators (DEAs) that swims
by body and/or caudal fin (BCF) propulsion. BCF is a promising locomotion
mechanism that potentially offers swimming at higher speeds and acceleration
rates, and efficient locomotion. The robot consists of laminated silicone layers
wherein two DEAs are used in an antagonistic configuration, generating undulating
fish-like motion. The design of the robot is guided by a mathematical model based
on the Euler-Bernoulli beam theory and takes account of the nonuniform geometry
of the robot and of the hydrodynamic effect of water. The modeling results were
compared with the experimental results obtained from the fish robot with a total
length of 150 mm, a thickness of 0.75 mm, and weight of 4.4 g. We observed that
the frequency peaks in the measured thrust force produced by the robot are
similar to the natural frequencies computed by the model. The peak swimming speed
of the robot was 37.2 mm/s (0.25 body length/s) at 0.75 Hz. We also observed that
the modal shape of the robot at this frequency corresponds to the first natural
mode. The swimming of the robot resembles real fish and displays a Strouhal
number very close to those of living fish. These results suggest the high
potential of DEA-based underwater robots relying on BCF propulsion, and
applicability of our design and fabrication methods.
PMID- 29957132
TI - Risk biomarkers enable precision in public health.
AB - Precision medicine uses biomarkers to diagnose disease. However, they can also be
used to measure risk of disease. Thus, biomarkers herald a new addition to public
health - Precision Public Health. We examine the implications. Risk biomarkers
are identified by analyzing population cohorts. They constitute risk factors in
mathematical 'Disease Risk Models'. The risk may be fixed as in a genetic
biomarker or variable as in some protein biomarkers. They help monitor current
risk of disease in an individual, thereby aiding efforts to reduce risk. In the
UK, the NHS Health Check system is a universal system for assessing risk and for
risk reduction. The system can now make use of modern biomarkers once appropriate
infrastructure and governance are in place.
PMID- 29956995
TI - Search for Physics Beyond the Standard Model in Events with High-Momentum Higgs
Bosons and Missing Transverse Momentum in Proton-Proton Collisions at 13 TeV.
AB - A search for physics beyond the standard model in events with one or more high
momentum Higgs bosons, H, decaying to pairs of b quarks in association with
missing transverse momentum is presented. The data, corresponding to an
integrated luminosity of 35.9 fb^{-1}, were collected with the CMS detector at
the LHC in proton-proton collisions at the center-of-mass energy sqrt[s]=13 TeV.
The analysis utilizes a new b quark tagging technique based on jet substructure
to identify jets from H->bb[over -]. Events are categorized by the multiplicity
of H-tagged jets, jet mass, and the missing transverse momentum. No significant
deviation from standard model expectations is observed. In the context of
supersymmetry (SUSY), limits on the cross sections of pair-produced gluinos are
set, assuming that gluinos decay to quark pairs, H (or Z), and the lightest SUSY
particle, LSP, through an intermediate next-to-lightest SUSY particle, NLSP. With
large mass splitting between the NLSP and LSP, and 100% NLSP branching fraction
to H, the lower limit on the gluino mass is found to be 2010 GeV.
PMID- 29957133
TI - Analysis of cysteine protease inhibitor gene (BmCPI) promoter activity in
silkworms using bac-to-bac baculovirus systems.
AB - A cysteine protease inhibitor of Bombyx mori (BmCPI) plays an important role in
pupation, molting, and dissociation of tissues. The present study identified and
analyzed the BmCPI promoter region to better understand its functional regulatory
mechanisms. Eight promoter fragments of different lengths were analyzed using an
improved Bac-to-Bac expression system. Luciferase activities were investigated
both in BmE cells and larval organisms after infection with the Bac-to-Bac
system, and similar changes in activity were observed in both models. Strong
activity was detected in the longest promoter (2005 bp, -1969 to +36), and
activity changed significantly with truncation of promoter length. An
electrophoretic mobility shift assay showed that the promoter region from -32 to
+6 bp played a critical role in activating the downstream gene promoter element,
where some potential elements were also predicted by informatics tools. The
findings offer a basic reference for the mechanism of transcriptional regulation
of BmCPI.
PMID- 29957137
TI - Smoking Behaviors in Arab Americans: Acculturation and Health Beliefs.
AB - INTRODUCTION: Arab Americans are a growing population in the United States. In
the 2011 American Community Survey, the U.S. Census Bureau reported there were
close to 1.8 million Arab Americans living within the United States, a 47%
increase in population size from 2000. According to the Arab American Institute,
currently, that estimate has grown to approximately 3.7 million. They have high
rates of smoking and low rates of smoking cessation. In this study, the
researchers investigated factors influencing desire to quit smoking among Arab
Americans, and their association with acculturation and health beliefs.
METHODOLOGY: Cross-sectional descriptive study investigating smoking behaviors
and factors influencing the desire to quit smoking among adult Arab American.
Data were collected to measure tobacco use, nicotine dependence, desire to quit
smoking, acculturation, and health beliefs. RESULTS: The sample ( N = 96) was 55%
female, mean age of 44 years (+/-14.79). The desire to quit smoking was
positively associated with perceived severity (p < .05) and susceptibility to
cancer (p < .05), perceived benefits of quitting smoking ( p < .01); and
negatively associated with smoking barriers (addiction barriers p < .05, external
barriers p = .27, internal barriers p < .05), and nicotine dependence (p < .05).
Being female, having a lower level of nicotine dependence, and a higher
perception of cancer severity predicted higher desire to quit smoking ( p < .01).
DISCUSSION: Smoking cessation intervention studies need to target appropriate
health beliefs, especially the high risk of cancer caused by smoking among Arab
Americans.
PMID- 29957134
TI - Impaired Angiogenic Supportive Capacity and Altered Gene Expression Profile of
Resident CD146+ Mesenchymal Stromal Cells Isolated from Hyperoxia-Injured
Neonatal Rat Lungs.
AB - Bronchopulmonary dysplasia (BPD), the most common complication of extreme preterm
birth, can be caused by oxygen-related lung injury and is characterized by
impaired alveolar and vascular development. Mesenchymal stromal cells (MSCs) have
lung protective effects. Conversely, BPD is associated with increased MSCs in
tracheal aspirates. We hypothesized that endogenous lung (L-)MSCs are perturbed
in a well-established oxygen-induced rat model mimicking BPD features. Rat pups
were exposed to 21% or 95% oxygen from birth to postnatal day 10. On day 12,
CD146+ L-MSCs were isolated and characterized according to the International
Society for Cellular Therapy criteria. Epithelial and vascular repair potential
were tested by scratch assay and endothelial network formation, respectively,
immune function by mixed lymphocyte reaction assay. Microarray analysis was
performed using the Affymetrix GeneChip and gene set enrichment analysis
software. CD146+ L-MSCs isolated from rat pups exposed to hyperoxia had decreased
CD73 expression and inhibited lung endothelial network formation. CD146+ L-MSCs
indiscriminately promoted epithelial wound healing and limited T cell
proliferation. Expression of potent antiangiogenic genes of the axonal guidance
cue and CDC42 pathways was increased after in vivo hyperoxia, whereas genes of
the anti-inflammatory Janus kinase (JAK)/signal transducer and activator of
transcription (STAT) and lung/vascular growth-promoting fibroblast growth factor
(FGF) pathways were decreased. In conclusion, in vivo hyperoxia exposure alters
the proangiogenic effects and FGF expression of L-MSCs. In addition, decreased
CD73 and JAK/STAT expression suggests decreased immune function. L-MSC function
may be perturbed and contribute to BPD pathogenesis. These findings may lead to
improvements in manufacturing exogenous MSCs with superior repair capabilities.
PMID- 29957141
TI - Intraventricular recurrence of a craniopharyngioma: case report.
AB - Craniopharyngiomas frequently recur locally or less commonly along the path of
prior resection. Ectopic recurrence is rare, although cases are reported along
the neuraxis spanning from the subgaleal space down to the S1 nerve root. This
case reports on a girl with a history of craniopharyngioma first resected at 23
months of age with two local suprasellar recurrences managed with repeat
craniotomy and external beam radiation therapy. At age 14 she complained of
worsening headaches and brain MRI demonstrated an enhancing 1.2-cm cystic lesion
in the posterior body of the left lateral ventricle. Pathology following
endoscopic resection of the lesion was consistent with an adamantinomatous
craniopharyngioma. This case report serves to describe the first reported
recurrence of a craniopharyngioma in the lateral ventricle and emphasizes the
need for a high index of suspicion along with long-term follow-up of patients
with a history of craniopharyngioma.
PMID- 29957139
TI - A Case of Severe Lumbar Necrotizing Soft Tissue Infection from an Ileal Pouch
Fistula.
AB - BACKGROUND: Necrotizing soft tissue infection (NSTI) is a rapidly progressive
infection characterized by tissue necrosis, septic shock, and is associated with
a high risk of death. Key aspects of successful treatment include early
recognition and emergent surgical source control. Necrotizing soft tissue
infection may occur from a range of etiologies but may also occur rarely from
gastrointestinal routes. We report a case of severe lumbar NSTI arising from an
ileal pouch fistula in a patient with inflammatory bowel disease. We report a
case of a 62-year-old male with a history of ulcerative colitis and restorative
proctocolectomy who presented with a severe NSTI of the lumbar region. METHODS:
Our operative approach focused on debridement of infected necrotic tissue and
abscess drainage to achieve source control. We elected to forego a transabdominal
approach during the initial operation given that source control but not source
elimination was deemed the initial priority. RESULTS: The patient subsequently
underwent a diverting ileostomy and pouch salvage. After a prolonged hospital
course, the patient recovered well. CONCLUSIONS: Fistulization from the
gastrointestinal tract is a rare but potential source of NSTI. It is not
necessary to address the fistula during the initial operation but should be done
promptly after the patient stabilizes. Prompt surgical debridement of infected
soft tissue as source control remains the cornerstone of the index operation.
PMID- 29957138
TI - Early Onset Prosthetic Valve Endocarditis: Experience at a Cardiothoracic
Surgical Hospital, 2006-2016.
AB - BACKGROUND: Early onset prosthetic valve endocarditis (EO-PVE) is an serious
complication associated with heart valve replacement surgery. OBJECTIVES: To
describe the epidemiologic, clinical, and laboratory profile of patients with EO
PVE in a cardiac surgical hospital. PATIENTS AND METHODS: A retrospective
analysis of an endocarditis database, implemented prospectively, with a post hoc
study driven by analysis of cases of adults with definite endocarditis occurring
up to 12 months after heart valve surgery. RESULTS: We identified 26 cases in
2,496 surgeries in the period 2006-2016. The average annual incidence was 1.04%.
The median time between valve replacement and the diagnosis of EO-PVE was 33 days
(interquartile range [IQR] 19.25-118.75). Biologic and mechanical prostheses were
affected in 53.8% and 46.2%, respectively. Rheumatic disease was present in 57.7%
of patients. The most common causative pathogens were Staphylococcus epidermidis
(23.1%). No Staphylococcus aureus infection was reported. Complications were
present in 73.1% of cases, including embolism (65.4%), acute renal failure
(38.5%), and heart failure (23.1%). The mortality rate at 30 days and 12 months
was 3.8% and 34.6%, respectively. CONCLUSIONS: In our cohort EO-PVE was an
serious complication of heart valve replacement with a high morbidity and
mortality, despite its low frequency.
PMID- 29957136
TI - Effect of Spatone Supplement on Endurance Capacity and Inflammatory Cytokines in
a Rapid Weight Control Program in University Wrestlers: A Pilot Study.
AB - In this pilot study, we investigated the effect of spatone, a naturally occurring
mineral water supplement, on endurance capacity and inflammatory cytokines in
wrestlers undergoing a rapid weight control program. Nine amateur university
wrestlers participated and were randomly divided into placebo- and spatone
treated groups. The study used a crossover design, including a 4-week washout
period. The rapid weight control program was focused on body weight loss, while
maintaining their athletic performance (muscular strength and cardiovascular
endurance). The initial body weight was 87.19 +/- 2.45 kg in the spatone-treated
group and 86.60 +/- 3.01 kg in the placebo group. After the rapid weight control
program, the body weight decreased to 83.56 +/- 2.71 kg (4.21% decrease) in the
spatone-treated group and 82.95 +/- 2.97 kg (4.16% decrease) in the placebo
group. However, there were no significant differences in body weight or body
composition between placebo- and spatone-treated groups. Endurance capacity
improved significantly in terms of VO2max and lactate accumulation after spatone
supplement. The interleukin (IL)-10, tumor necrosis factor (TNF)-alpha, and IL-6
concentrations were not altered with spatone treatment or placebo in the rapid
weight-loss condition; however, a positive relationship (R = 0.643, P = .023) was
observed between the change in IL-6 and VO2max. Thus, our results are consistent
with prior studies in that spatone supplementation could protect against iron
loss induced by intense training, considering that spatone affects the modulation
of inflammatory cytokines and exercise capacity. These preliminary results serve
to facilitate the planning for the nutritional application of spatone with their
exercise program for wrestlers.
PMID- 29957140
TI - Secondary overtriage of pediatric neurosurgical trauma at a Level I pediatric
trauma center.
AB - The authors looked at all of the pediatric patients with a head injury who were
transferred from other hospitals to their own over 12 years and tried to identify
factors that would allow patients to stay closer to home at their local hospitals
and not be transferred. Many patients with isolated, nondisplaced skull fractures
or negative CT imaging likely could have avoided transfer. While hospitals should
be cautious, this may help families stay closer to home.
PMID- 29957135
TI - Serological Survey of Getah Virus in Domestic Animals in Yunnan Province, China.
AB - We detected neutralizing antibodies of Getah virus (GETV) in serum specimens of
domestic animals collected from Yunnan Province in China. Antibodies were
detected in serum specimens of chicken, duck, dairy cattle, pig, and beef cattle.
The positive rate of antibodies in pig and beef cattle was high (46-72%), with
titers of 1:640-1:2560. These results suggest that there may be a large number of
host animals for GETV in the local area. It is important to improve the
monitoring of the incidence of GETV infection in domestic animals, in particular
among pigs and beef cattle, by surveillance for animal illness and testing of
sick animals.
PMID- 29957143
TI - Retraction of: Hair Iodine for Human Iodine Status Assessment, Thyroid
24(6);2014:1018-1026; DOI: 10.1089/thy.2012.0499.
PMID- 29957142
TI - Temporal response profiles of serum ubiquitin C-terminal hydrolase-L1 and the 145
kDa alpha II-spectrin breakdown product after severe traumatic brain injury in
children.
AB - OBJECTIVE: Traumatic brain injury (TBI) is the leading cause of acquired
disability among children. Brain injury biomarkers may serve as useful diagnostic
and prognostic indicators for TBI. Levels of ubiquitin C-terminal hydrolase-L1
(UCH-L1) and the 145-kDa alpha II-spectrin breakdown product (SBDP-145) correlate
with outcome in adults after severe TBI. The authors conducted a pilot study of
these biomarkers in children after severe TBI to inform future research exploring
their utility in this population. METHODS: The levels of UCH-L1 and SBDP-145 were
measured in serum, and UCH-L1 in CSF from pediatric patients after severe TBI
over 5 days after injury. Both biomarkers were also measured in age-matched
control serum and CSF. RESULTS: Adequate numbers of samples were obtained in
serum, but not CSF, to assess biomarker temporal response profiles. Using
patients with samples from all time points, UCH-L1 levels increased rapidly and
transiently, peaking at 12 hours after injury. SBDP-145 levels showed a more
gradual and sustained response, peaking at 48 hours. The median serum UCH-L1
concentration was greater in patients with TBI than in controls (median [IQR] =
361 [187, 1330] vs 147 [50, 241] pg/ml, respectively; p < 0.001). Receiver
operating characteristic (ROC) analysis revealed an AUC of 0.77. Similarly, serum
SBDP-145 was greater in children with TBI than in controls (median [IQR] = 172
[124, 257] vs 69 [40, 99] pg/ml, respectively; p < 0.001), with an ROC AUC of
0.85. When only time points of peak levels were used for ROC analysis, the
discriminability of each serum biomarker increased (AUC for UCH-L1 at 12 hours =
1.0 and for SBDP-145 at 48 hours = 0.91). Serum and CSF UCH-L1 levels correlated
well in patients with TBI (r = 0.70, p < 0.001). CONCLUSIONS: Findings from this
exploratory study reveal robust increases of UCH-L1 and SBDP-145 in serum and UCH
L1 in CSF obtained from children after severe TBI. In addition, important
temporal profile differences were found between these biomarkers that can help
guide optimal time point selection for future investigations of their potential
to characterize injury or predict outcomes after pediatric TBI.
PMID- 29957144
TI - Areca nut trade, globalisation and its health impact: perspectives from India and
South-east Asia.
AB - AIM: Areca nut (AN) is consumed globally by 600 million people, and 10%-20% of
the world population uses betel quid, a preparation containing areca nut. India
and other South-east Asian countries are the largest consumers of AN in the
world. The aim of this article is to review the economic impact and oral health
effects of the consumption of AN. It will also discuss the role of dentists and
auxiliary healthcare providers for increasing public awareness and the need for a
strong public health policy. METHOD: To address the concerned area, PubMed,
Scopus and Google Scholar databases were explored from the year 1965 until 2017.
Studies focusing on various aspects of AN only, and articles published in English
were included. Anecdotal reports, case reports and unpublished data were
excluded. RESULTS AND DISCUSSION: This narrative review suggests India is the
world's largest producer of AN along with the largest AN consuming population
followed by other South-east Asian countries. AN chewing causes oral submucous
fibrosis (OSF) and it is most commonly observed in people of India and South-east
Asia. AN use is associated with various social and unsocial aspects. Dentists and
dental auxiliaries can increase the knowledge and awareness of a health issue
(OSF) among the target audience as well as the detrimental effects of AN chewing.
CONCLUSION: There is a need for more aggressive public health measures and
dentists and dental auxiliaries should be employed to bring awareness to the
general public regarding AN use.
PMID- 29957145
TI - Minimally invasive posterior cervical foraminotomy with tubes to prevent
undesired fusion: a long-term follow-up study.
AB - OBJECTIVE: The objective of this study was to compare anterior cervical
discectomy and fusion (ACDF) and minimally invasive posterior cervical
foraminotomy (MI-PCF) with tubes for the treatment of cervical radiculopathy in
terms of the 1) overall revision proportion, 2) index and adjacent level revision
rates, and 3) functional outcome scores. METHODS: The authors retrospectively
reviewed the records of consecutive patients who had undergone ACDF or MI-PCF at
a single institution between 2009 and 2014. Patients treated for cervical
radiculopathy without myelopathy and with a minimum 2-year follow-up were
compared according to the procedure performed for their pathology. Primary
outcome measures included the overall rate of revision with fusion and overall
revision proportion as well as the rate of index and adjacent level revisions per
year. Secondarily, self-reported outcome measures-Neck Disability Index (NDI) and
visual analog scale (VAS) for arm (VASa) and neck (VASn) pain-at the preoperative
and postoperative evaluations were analyzed. Standard binomial and categorical
comparative analyses were performed. RESULTS: Forty-nine consecutive patients
were treated with MI-PCF, and 210 consecutive patients were treated with ACDF.
The mean follow-up for the MI-PCF cohort was 42.9 +/- 6.6 months (mean +/- SD)
and for the ACDF cohort was 44.9 +/- 10.3 months. There was no difference in the
overall revision proportion between the two cohorts (4 [8.2%] of 49 MI-PCF vs. 12
[5.7%] of 210 ACDF, p = 0.5137). There was no difference in the revision rate per
level per year (3.1 vs. 1.7, respectively, p = 0.464). Moreover, there was no
difference in the revision rate per level per year at the index level (1.8 vs.
0.7, respectively, p = 0.4657) or at an adjacent level (1.3 vs. 1.1, p = 0.9056).
Neither was there a difference between the cohorts as regards the change from
preoperative to final postoperative functional outcome scores (NDI, VASa, VASn).
CONCLUSIONS: Minimally invasive PCF for the treatment of cervical radiculopathy
demonstrates rates of revision at the index and adjacent levels similar to those
following ACDF. In order to confirm the positive efficacy and cost analysis
findings in this study, future studies need to extend the follow-up and show that
the rate of revision with fusion does not increase substantially over time.
PMID- 29957146
TI - Posterior percutaneous full-endoscopic cervical discectomy under local anesthesia
for cervical radiculopathy due to soft-disc herniation: a preliminary clinical
study.
AB - The authors describe the outcomes of 25 patients, the procedure's surgical steps,
and the potential advantages of using the posterior percutaneous full-endoscopic
cervical discectomy under local anesthesia. They believe this technique may be a
new alternative in the treatment of selected patients with cervical radiculopathy
due to soft-disc herniation.
PMID- 29957147
TI - The five-repetition sit-to-stand test: evaluation of a simple and objective tool
for the assessment of degenerative pathologies of the lumbar spine.
AB - OBJECTIVE: Recently, objective functional tests have generated interest since
they can supplement an objective dimension to clinical assessment. The five
repetition sit-to-stand (5R-STS) test is a quick and objective tool that tests
movements frequently used in everyday life. The aim of this prospective study was
to evaluate the validity and reliability of the 5R-STS test in patients with
degenerative pathologies of the lumbar spine. METHODS: Patients and healthy
volunteers completed the standardized 5R-STS, Roland-Morris Disability
Questionnaire (RMDQ), Oswestry Disability Index (ODI), visual analog scale (VAS)
for back and leg pain, and EQ-5D for health-related quality of life (HRQOL). To
assess convergent validity, the 5R-STS test times were correlated with these
questionnaires. RESULTS: Overall, 157 patients and 80 volunteers were enrolled.
Direct correlation with RMDQ (r = 0.49), ODI (r = 0.44), and VAS for back pain (r
= 0.31) and indirect correlation with the EQ-5D index (r = -0.41) were observed
(p < 0.001). The 5R-STS test showed no correlation with VAS for leg pain and EQ
5D VAS (p > 0.05). In 119 individuals, the 5R-STS test demonstrated excellent
test-retest reliability with an intraclass correlation coefficient of 0.98. The
upper limit of normal, distinguishing patients with and without objective
functional impairment, was identified as 10.35 seconds. A severity stratification
classified patients with test times of 10.5-15.2, 15.3-22.0, or greater than 22.0
seconds as having mild, moderate, or severe functional impairment, respectively.
CONCLUSIONS: The 5R-STS test is a simple and effective tool to describe objective
functional impairment. A patient able to perform the test in 10.4 seconds can be
considered to have no relevant objective functional impairment. Clinical trial
registration no.: NCT03303300 (clinicaltrials.gov).
PMID- 29957149
TI - Benevolent Sexism and Mate Preferences: Why Do Women Prefer Benevolent Men
Despite Recognizing That They Can Be Undermining?
AB - Benevolent sexism (BS) has detrimental effects on women, yet women prefer men
with BS attitudes over those without. The predominant explanation for this
paradox is that women respond to the superficially positive appearance of BS
without being aware of its subtly harmful effects. We propose an alternative
explanation drawn from evolutionary and sociocultural theories on mate
preferences: Women find BS men attractive because BS attitudes and behaviors
signal that a man is willing to invest. Five studies showed that women prefer men
with BS attitudes (Studies 1a, 1b, and 3) and behaviors (Studies 2a and 2b),
especially in mating contexts, because BS mates are perceived as willing to
invest (protect, provide, and commit). Women preferred BS men despite also
perceiving them as patronizing and undermining. These findings extend
understanding of women's motives for endorsing BS and suggest that women prefer
BS men despite having awareness of the harmful consequences.
PMID- 29957148
TI - Congenital Brucellosis: A Systematic Review of the Literature.
AB - BACKGROUND: Knowledge of the spectrum of presentations and the outcome of
congenital brucellosis should expedite diagnosis and improve prognostication.
METHODS: A systematic review of literature of cases of congenital brucellosis was
performed on October 10, 2017 (registered as PROSPERO CRD42017072061). RESULTS: A
case seen by the authors was added to the review, yielding 44 reported cases of
which 22 (50%) were from Turkey, Saudi Arabia, or Kuwait. For cases with the
gestational age reported, 23 of 37 (62%) were preterm. The species was Brucella
melitensis in 35 cases, Brucella abortus in 3 cases and not documented in 6
cases. The diagnosis was based on a positive blood culture from the first day of
life in 20 cases (45%). Presentation was usually typical for a bacteremic infant
of that GA, but two infants were asymptomatic at diagnosis. There were two
recurrences and seven deaths (six in preterm infants), but the role of Brucella
infection in the deaths was not clear. CONCLUSION: Brucellosis remains a concern
in endemic countries, adversely affecting pregnancy and very rarely causing
neonatal infection. Prematurity appeared to be the prime cause of death in
neonates with congenital brucellosis.
PMID- 29957150
TI - The Impact of Telemedicine on Teamwork and Workload in Pediatric Resuscitation: A
Simulation-Based, Randomized Controlled Study.
AB - BACKGROUND: Telemedicine provides access to specialty care to critically ill
patients from a geographic distance. The effects of using telemedicine on (1)
teamwork and communication (TC), (2) task workload during resuscitation, and (3)
the processes of critical care have not been well described. OBJECTIVES: To
evaluate the impact of telemedicine on (1) TC, (2) task workload during a
resuscitation, and (3) the processes of critical care during a simulated
pediatric resuscitation. METHODS: Prospective single-center randomized trial.
Teams of two physicians (senior and junior resident) and two standardized
confederate nurses were randomized to either telemedicine (telepresent senior
physician team leader) or usual care (both physicians in the room) during a
simulated infant resuscitation. Simulations were video recorded and assessed for
teamwork, workload, and processes of care using the Simulated Team Assessment
Tool (STAT), the NASA Task Load Index (NASA-TLX) tool, and time between onset of
ventricular fibrillation and defibrillation, respectively. RESULTS: Twenty teams
participated. There was no difference in teamwork between the groups (mean STAT
score 72% vs. 69%; p = 0.383); however, there was a significantly greater
workload in the telemedicine group (mean TLX score 56% vs. 48%, p = 0.020). Using
linear regression, no difference was found in time-to-defibrillation between
groups (p = 0.671), but higher teamwork scores predicted faster time to
defibrillation (p = 0.020). CONCLUSIONS: In this simulation-based study, a
telepresent team leader was associated with increased team workload compared to
usual care. However, no differences were noted in teamwork and processes of care
metrics.
PMID- 29957151
TI - Perceptions of a Peer Modeling Workplace Physical Activity Intervention for
Women.
AB - A workplace physical activity (PA) study tested a novel use of peers to deliver
the intervention. Peer models provided vicarious experience for living physically
active lifestyles to a group of inactive women. The purpose of this study was to
describe participants' perceptions of the peer modeling intervention. Nine women
from the intervention group ( n = 26) participated in a 90-minute focus group.
Qualitative description using thematic analysis was used to identify themes from
the focus group transcript. Two themes about the intervention were "I am left
wanting more" and "focus on food." Two themes about the peer models were "real
people" and "it is doable." Focus group participants perceived the peer modeling
PA intervention favorably; however, they desired more attention to healthy eating
and more time with peer models. Replication of the study accounting for themes
identified by focus group participants is needed to strengthen the peer modeling
intervention.
PMID- 29957152
TI - The Use of Chitosan-Coated Membrane Vesicles for Immunization Against Salmonid
Rickettsial Septicemia in an Adult Zebrafish Model.
AB - The introduction of fish vaccination has had a tremendous impact on the
aquaculture industry by providing an important measurement in regard to disease
control. Infectious diseases caused by intracellular pathogens do, however,
remain an unsolved problem for the industry. This is in many cases directly
connected to the inability of vaccines to evoke a cellular immunity needed for
long-term protection. Thus, there is a need for new and improved vaccines and
adjuvants able to induce a strong humoral and cellular immune response. We have
previously shown that membrane vesicles (MVs) from the intracellular fish
pathogen Piscirickettsia salmonis are able to induce a protective response in
adult zebrafish, but the incorporation of an adjuvant has not been evaluated. In
this study, we report the use of chitosan as an adjuvant in combination with the
P. salmonis-derived MVs for improved immunization against P. salmonis. Both free
chitosan and chitosan-coated MVs (cMVs) were injected into adult zebrafish and
their efficacy evaluated. The cMVs provided a significant protection (p < 0.05),
while a small but nonsignificant reduction in mortalities was registered for fish
injected with free chitosan. Both free chitosan and the cMVs were shown to induce
an increased immune gene expression of CD 4, CD 8, MHC I, Mpeg1.1, TNFalpha, IL
1beta, IL-10, and IL-6, but to a higher degree in the cMV group. Taken together,
the results indicate a potential use of chitosan-coated MVs for vaccination, and
that zebrafish is a promising model for aquaculture-relevant studies.
PMID- 29957153
TI - Divergent Chromosome Evolution in Hypostominae Tribes (Siluriformes:
Loricariidae): Correlation of Chromosomal Data with Morphological and Molecular
Phylogenies.
AB - Hypostominae is the largest subfamily of Loricariidae, and is widely distributed
throughout the Neotropic. In the present article, we analyze three Loricariidae
species that were considered part of Hypostominae, from three different tribes,
to discuss chromosome evolution in this fish group and to review the existent
data for the subfamily. Rhinelepis aspera had 54 chromosomes (20m + 26sm+8st),
whereas Pterygoplichthys ambrosettii and Megalancistrus parananus had 52
chromosomes, with 16m+24sm+8st+4a and 18m+24sm+10st, respectively. The
karyological data were compared with existent phylogenetic hypotheses, indicating
a common ancestor with 2n = 52 chromosomes for the Acanthicus, Hemiancistrus, and
Peckoltia clades, as well as for Hypostomini. Shared recurrent characteristics of
the tribes are discussed, as well as peculiarities of genera Ancistrus and
Hypostomus. We propose that the occurrence of fragile sites demonstrated for
Ancistrus facilitated chromosomal rearrangements that decreased the proportion of
metacentric/submetacentric chromosomes and the diploid number in many species
from this genus. Although Hypostominae is usually considered a subfamily with
derived chromosome features, our revision shows that this is valid only for
Hypostomini and Ancistrini, which have a divergent chromosome evolution from
other tribes that seems to conserve plesiomorphic features.
PMID- 29957155
TI - Utilizing Patient-Specific Factors to Predict Costs in Home-Based Medicare Part B
Outpatient Physical Therapy.
AB - The US health care system faces rising costs related to population aging, among
other factors. One aspect of the high costs related to aging is Medicare
outpatient therapy expenditures, which in 2010 totaled $5.642B for ~4.7 million
beneficiaries. Given the magnitude of these costs and the need to maximize value,
this study developed and tested a predictive model of outpatient therapy costs.
Retrospective analysis was performed on electronic medical record data from
October 31, 2014-September 30, 2016 for 15,468 Medicare cases treated by physical
therapists associated with a large, national rehabilitation provider. The
analysis was a multiple linear regression of cost per case by 27 predictor
variables: age group, sex, recent hospitalization, community vs. facility
residence, the 10 states served, time from admission to initial evaluation,
initial functional limitation reporting level, functional limitation reporting
category, and 9 chronic conditions. The model was designed to be predictive and
includes only variables available at the start of a case. The model was
statistically significant (P < .0001) but explained only 7.4% of the variance in
cost. Of the predictor variables, 16 had statistically significant effects. Those
most highly predictive included state in which service was provided (8 of the 16
effects), and 3 variables indicating physical functioning at initial evaluation
(initial functional limitation category and level, and residence in community vs.
facility). There is need for more research focusing on the effects of specific
types of treatment, and also for a more proactive model for outpatient therapy
reimbursement that emphasizes prevention as well as treatment.
PMID- 29957154
TI - Epidemiology and management of foodborne nematodiasis in the European Union,
systematic review 2000-2016.
AB - BACKGROUND: Foodborne nematodiasis are caused by the ingestion of food
contaminated by helminths. In Europe, these diseases are present in all
countries. OBJECTIVES: To review the available data on epidemiology and
management of foodborne nematodiasis in the European Union, detect any trends and
determine the possible causes of the observed changes. METHODS: A review of
available literature published between 2000 and 2016 was conducted. RESULTS: Out
of 1523 cases described in the literature, 1493 cases were autochthonous and 30
cases were imported. The detected parasites were Toxocara spp (34.7%), Ascaris
lumbricoides (27.1%), Trichinella spp (21.9%), Anisakis spp (15.5%) and
Angiostrongylus cantonensis (0.8%). CONCLUSIONS: Foodborne nematodiasis remains a
public health challenge for the European Union. Autochthonous cases of
nematodiasis present the greatest health risk within the European Union.
Foodborne nematodes due to lack of hygiene in food processing are diseases that
can be avoided by increasing.
PMID- 29957156
TI - Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults and
adolescents-a life-threatening disease: analysis of 133 cases from a single
center.
AB - OBJECTIVES: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis is
the most common type of infection-associated HLH. Previous studies were focused
on pediatric EBV-HLH patients, therefore there lack of adult data. METHOD: We
performed a retrospective analysis of 133 EBV-HLH patients (>=14 years old) in
Beijing Friendship Hospital from March 2009 to April 2016 to evaluate the
clinical manifestation and the effects and prognosis of existing regimens of EBV
HLH in adult and adolescents. RESULTS: Of these patients, 91 male and 42 female
cases had a median age of 26 (14-77) years. EBV-DNA load on admission was at a
median of 6.6E + 05 IU/ml. The one-year mortality of these patients was 78%. 112
patients received the HLH-94/04 regimen as the initial treatment, 52 patients
(46.43%) had response. Of the 6 patients who received the L-DEP regimen as the
initial treatment, 5 patients (83.33%) had response. The rest 15 patients
received initial treatment without etoposide, 5 cases achieved PR. 69 refractory
or relapsed patients received DEP or L-DEP regimen, 55 (79.71%) cases had
response. In addition, who received the L-DEP regimen, with the overall response
rate significantly higher than the DEP regimen (88.37% VS 65.38%, P = 0.031). 36
out of 133 EBV-HLH patients eventually received allo-HSCT, with the overall
survival rate of 52.78%. In summary, EBV-HLH is a highly lethal disease.
CONCLUSION: DEP/L-DEP was a good salvage treatment. L-DEP might be a more
effective first-line initial regimen than HLH-94/04 regimen for EBV-HLH. Finally,
allo-HSCT is an effective radical treatment for EBV-HLH.
PMID- 29957157
TI - Kidney Donation From a Patient Who Underwent Endovascular Aneurysm Repair.
AB - Organ shortage is the greatest challenge facing the field of organ
transplantation in Korea. There are no reports of patients who have undergone
endovascular aneurysm repair being considered as kidney donors. We successfully
performed kidney transplant procedures in a 62-year-old man and a 57-year-old man
using kidneys recovered from a 67-year-old female brain-dead donor who underwent
endovascular aneurysm repair 6 months before organ retrieval. To the best of our
knowledge, this is the first report of transplants performed with organs from a
donor who previously underwent endovascular aneurysm repair.
PMID- 29957158
TI - Comparison of Resection and Liver Transplant in Treatment of Hepatocellular
Carcinoma.
AB - OBJECTIVES: Hepatic resection and liver transplant are regarded as 2 potentially
curative treatments for hepatocellular carcinoma. Here, we compared both options
in patients with hepatocellular carcinoma secondary to cirrhosis seen at a single
center over 12 years. MATERIALS AND METHODS: We evaluated early complications and
survival of patients with hepatocellular carcinoma treated with liver transplant
(57 patients) or hepatic resection (36 patients) at our center between 1998 and
2010. RESULTS: The 34-month mean follow-up period was similar for both treatment
groups. The liver transplant group had a longer hospital stay than the hepatic
resection group (P ? .001). Patients with Child-Turcotte-Pugh A stage were
treated by hepatic resection more than by liver transplant (P ? .001),with Child
Turcotte-Pugh B stage patients treated by liver transplant more than by hepatic
resection (P = .03). All patients with Child-Turcotte-Pugh C stage had liver
transplant. Both treatment groups had similar postoperative complications and
early postoperative mortality rates, but liver transplant resulted in longer
overall (P = .001) and higher event-free (P = .001) survival than hepatic
resection. Among the liver transplant group, 57.8% of patients met the Milan
criteria. Patients who met Milan criteria were treated by liver transplant
statistically more than hepatic resection, and these patients had longer overall
survival (P = .01) and higher event-free survival (P ? .001) than patients who
had hepatic resection. Hepatocellular carcinoma recurrence rates were higher
after hepatic resection (P = .232). CONCLUSIONS: In patients with hepatocellular
carcinoma, hospital stay was longer after liver transplant, but morbidity and
mortality rates for liver transplant versus hepatic resection were similar.
However, overall and event-free survival rates were better after liver transplant
than after hepatic resection. These results suggest that liver transplant should
be considered as the primary treatment option for patients with hepatocellular
carcinoma secondary to cirrhosis.
PMID- 29957159
TI - Extracorporeal Membrane Oxygenation Therapy-Assisted Cardiopulmonary
Resuscitation and Successful Bridging to Cardiac Retransplant for Cardiac
Allograft Vasculopathy.
AB - Extracorporeal membrane oxygenation therapy is being used increasingly in
different areas. It has become an indispensable assistant to clinicians for
hypoxic pulmonary disorders, cardiogenic shock, resuscitation, and during cardiac
surgery. In this case report, we describe a patient who is bridged to successful
cardiac retransplant under extracorporeal membrane oxygenation therapy support
after extracorporeal membrane oxygenation therapy-assisted cardiopulmonary
resuscitation.
PMID- 29957160
TI - Multifocal Soft Tissue Cryptococcosis in a Renal Transplant Recipient: The
Importance of Suspecting Atypical Pathogens in the Immunocompromised Host.
AB - Cryptococcal infection has been documented in 2.8% of solid-organ transplant
recipients, with the median time to disease onset being 21 months. Renal
transplant recipients account for the majority of cases. Most patients present
with central nervous system or disseminated disease, with only a minority having
cutaneous manifestations. We present the case of a 47-year-old female renal
transplant recipient who presented with refractory acute cellulitis 7 months
after transplant. She had received thymoglobulin induction and was on a
maintenance immunosuppressive regimen of tacrolimus, mycophenolic acid, and
prednisone (5 mg/d). She did not respond to broad-spectrum antibacterial therapy
for presumed bacterial cellulitis. Skin and soft tissue biopsies subsequently
showed the presence of yeast; Cryptococcus neoformans was recovered in culture.
Blood cultures, chest radiography, and cerebrospinal fluid sampling were
negative, which resulted in a diagnosis of multifocal soft tissue cryptococcosis,
a form of disseminated disease. Serum cryptococcal antigen testing was strongly
positive (>= 1:2560). The patient's immunosuppression was reduced, and she
received treatment with liposomal amphotericin B and flucytosine for 2 weeks,
which resulted in symptomatic improvement. This was followed by 1 year of
consolidation and subsequent maintenance therapy with fluconazole. This case
should increase awareness of the broader differential diagnosis of soft tissue
infection in immunocompromised patients. Her case mimicked bacterial cellulitis,
which delayed administration of effective therapy. Although our patient was
initially diagnosed via biopsy, early clinical suspicion and serum cryptococcal
antigen testing can lead to the correct diagnosis more rapidly. As transplant
patients return to their community providers, heightened vigilance for unusual
infections and presentations is warranted. The possibility of a cryptococcal
cause for acute soft tissue infection should be considered, even in the absence
of pulmonary or central nervous system involvement.
PMID- 29957161
TI - Cissus quadrangularis-Induced Thrombocytopenia in a Renal Allograft Recipient.
AB - An elderly male renal allograft recipient presented with thrombocytopenia. He had
a kidney transplant for diabetic kidney disease and was on azathioprine and
prednisolone. He had taken Cissus quadrangularis capsules for backache. A bone
marrow aspiration to evaluate the cause of thrombocytopenia showed megakaryocyte
hyperplasia, suggesting peripheral destruction. Repeat platelet counts after
stopping Cissus quadrangularis showed normal levels.
PMID- 29957162
TI - Kaposi Varicelliform Eruption Associated With Chickenpox in a Liver Transplant
Recipient.
AB - A 43-year-old male patient developed varicella virus (chickenpox) 4 months after
receiving a liver transplant. Within 5 days of complete recovery, he presented
with widespread cutaneous vesicular eruptions involving the face, back, abdomen,
and upper extremities. Tzanck smear showed ground glass inclusions in the nuclei
of multinucleated giant cells, suggestive of viral pathology. The patient was
subsequently diagnosed with Kaposi varicelliform eruption, a rare dermatologic
emergency. He was treated with high-dose intravenous acyclovir and fully
recovered.
PMID- 29957164
TI - ROCK Y-27632 Inhibitor, Ascorbic Acid, and Trehalose Increase Survival of Human
Wharton Jelly Mesenchymal Stem Cells After Cryopreservation.
AB - OBJECTIVES: Wharton jelly mesenchymal stem cells are good candidates for
application in different aspects of regenerative medicine, and their long-time
banking is important. In this study, the effects of trehalose, ascorbic acid, and
Y-27632 on proliferation and survival rate of these cells after cryopreservation
were investigated. MATERIALS AND METHODS: Mesenchymal stem cells were isolated
from human umbilical cord Wharton jelly and frozen using a slow-rate cooling
process. Different concentrations of trehalose (35, 75, and 125 mM), ascorbic
acid (0.06, 0.125, 0.25, and 0.5 mM), and Y-27632 (10 MUM) were used to treat
culture medium and/or to supplement freezing medium. Assessment of cell viability
after thawing was performed using Trypan blue staining, and MTT assay was
performed to measure the cell proliferation rate. RESULTS: We observed
significantly increased postthaw viability, increased cell proliferation, and
decreased doubling time of cells when 75 mM trehalose, 0.25 and 0.5 mM ascorbic
acid, and 10 mM Y-27632 were used. In addition, increased viability,
proliferation, and attachment were observed after 24 hours of pretreatment with
these cryoprotective agents and when they were added to conventional freezing
medium. CONCLUSIONS: The use of different cryoprotective agents in culture and
freezing media could be useful for long-term storage of Wharton jelly mesenchymal
stem cells.
PMID- 29957163
TI - Detection of Hepatis C Virus-Related Immunologic Markers and Their Impact on
Outcomes of Living-Donor Kidney Transplant Recipients.
AB - OBJECTIVES: Liver disease is an important cause of morbidity and mortality among
recipients of transplanted organs. In addition to the liver, hepatitis C virus
infection has a significant prevalence among recipients of kidney transplant and
is related to worse graft and recipient survival as the kidney is an important
component of the hepatitis C virus clinical syndrome. MATERIALS AND METHODS: This
retrospective single center study included 336 patients with end-stage renal
disease who received a kidney transplant at the Mansoura Urology and Nephrology
Center from January 1992 to December 1995. Of 336 patients, 63 were excluded, and
the remaining 273 patients were divided into 3 groups: viremic active (72
patients), viremic inactive (108 patients), and nonviremic (93 patients).
Division of patients was based on hepatitis C virus RNA complement level (C3
and/or C4 consumption), circulating cryoglobulins, and rheumatoid factor
detection. RESULTS: Our study showed insignificant differences regarding patient
characteristics and demographic data among the study groups but significantly
higher incidence of transaminitis in viremic (active and inactive) patients.
Nonsignificant differences were found regarding proteinuria among the 3 groups,
including among those who had levels in either nephrotic or nonnephrotic ranges.
Biopsy-proven acute rejection episodes among the 3 groups of recipients were
statistically comparable, with significantly higher frequency of chronic
rejection episodes among viremic active patients. Nonviremic recipients had
significantly lower serum creatinine levels than viremic (active and inactive)
recipients. Patient and graft survival results were comparable among the groups.
CONCLUSIONS: Presence of hepatitis C virus immunologic markers does not have a
significant effect on patient and graft survival; however, it may be a clue for
long-term incidence of chronic rejection.
PMID- 29957165
TI - Patient Sex in the Setting of Liver Transplant in Alcoholic Liver Disease.
AB - OBJECTIVES: The aim of this study was to analyze alcoholic cirrhosis in women who
were to undergo liver transplant, including their biochemical and clinical
characteristics, main complications, survival rates, and main causes of death
compared with men with alcoholic cirrhosis. MATERIALS AND METHODS: Our study
included 400 patients with alcoholic cirrhosis, which we divided according to sex
and viral infections. Biochemical parameters and the presence and degree of
ascites and encephalopathy, liver function status, and liver rejection and
survival rates were analyzed from 1 to 10 years and the main cause of death at 10
years. RESULTS: Patients with nonviral alcoholic cirrhosis and liver transplant
had significantly better survival rates (84.1%) at 1 year versus those with viral
alcoholic cirrhosis (74.5%; P = .036). Men with nonviral alcoholic cirrhosis
(14%) and women with hepatitis C virus (29%) had the lowest short-term survival
rates. In long-term survival analysis, the lowest rate was observed in women with
nonviral alcoholic cirrhosis (26.1%), and the highest rate was observed in women
with hepatitis C virus (42.9%). Liver graft failure was one of the main causes of
death in male patients (19.5%). CONCLUSIONS: Women with alcoholic cirrhosis
showed a higher rate of ascites and encephalopathy but lower liver graft
rejection than men with alcoholic cirrhosis. Survival rates were similar between
men and women, although slightly lower in women who had hepatitis C virus.
PMID- 29957166
TI - Helminth community and host dynamics in northern bobwhites from the Rolling
Plains Ecoregion, U.S.A.
AB - One hundred and sixty-one northern bobwhites (Colinus virginianus; hereafter
'bobwhite') were examined from the Rolling Plains ecoregion of Texas and western
Oklahoma from 2011 to 2013. Complete necropsies yielded 13 species, of which two
are new host (Gongylonema phasianella) and region (Eucoleus contortus) records
and three (Dispharynx nasuta, Tetrameres pattersoni and Oxyspirura petrowi) are
known to cause morbidity and mortality. Of the species found, Aulonocephalus
pennula commonly occurred, Oxyspirura petrowi was intermediate in prevalence, and
the remaining species were rare. Species richness was similar compared to studies
from the southeastern U.S., but higher than studies from the same region. In
addition, 12 of the 13 species were heteroxenous helminths, supporting the theory
that heteroxenous helminths in semi-arid regions are more successful than
monoxenous helminths. Prevalence and abundance of A. pennula and O. petrowi were
higher in adult bobwhites than in juveniles. Abundance of A. pennula and O.
petrowi was higher at southern locations compared to northern locations in the
study area. Our study is the first to provide a current assessment of the
bobwhite helminth community across the Rolling Plains ecoregion of the U.S.
PMID- 29957167
TI - Young adult mental health and functional outcomes among individuals with
remitted, persistent and late-onset ADHD.
AB - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is associated with
mental health problems and functional impairment across many domains. However,
how the longitudinal course of ADHD affects later functioning remains
unclear.AimsWe aimed to disentangle how ADHD developmental patterns are
associated with young adult functioning. METHOD: The Environmental Risk (E-Risk)
Longitudinal Twin Study is a population-based cohort of 2232 twins born in
England and Wales in 1994-1995. We assessed ADHD in childhood at ages 5, 7, 10
and 12 years and in young adulthood at age 18 years. We examined three
developmental patterns of ADHD from childhood to young adulthood - remitted,
persistent and late-onset ADHD - and compared these groups with one another and
with non-ADHD controls on functioning at age 18 years. We additionally tested
whether group differences were attributable to childhood IQ, childhood conduct
disorder or familial factors shared between twins. RESULTS: Compared with
individuals without ADHD, those with remitted ADHD showed poorer physical health
and socioeconomic outcomes in young adulthood. Individuals with persistent or
late-onset ADHD showed poorer functioning across all domains, including mental
health, substance misuse, psychosocial, physical health and socioeconomic
outcomes. Overall, these associations were not explained by childhood IQ,
childhood conduct disorder or shared familial factors. CONCLUSIONS: Long-term
associations of childhood ADHD with adverse physical health and socioeconomic
outcomes underscore the need for early intervention. Young adult ADHD showed
stronger associations with poorer mental health, substance misuse and
psychosocial outcomes, emphasising the importance of identifying and treating
adults with ADHD.Declaration of interestNone.
PMID- 29957168
TI - Paenibacillus elymi sp. nov., isolated from the rhizosphere of Elymus
tsukushiensis, a plant native to the Dokdo Islands, Republic of Korea.
AB - Strain KUDC6143T was isolated from the rhizosphere of Elymus tsukushiensis, a
plant native to the Dokdo Islands, Republic of Korea. Cells of this bacterial
strain were Gram-positive, endospore-forming, motile and rod-shaped. The strain
was capable of growth at a temperature of 25-45 degrees C and at a pH of 6.0
12.0; it showed an optimal growth at a temperature of 30 degrees C and at a pH
of 7.0. In addition, it grew on a tryptic soy agar and in a tryptic soy broth
containing less than 4.0 % NaCl (w/v). The cell length ranged from 2.0 to 2.7 um.
KUDC6143T was catalase-negative and oxidase-positive, and it hydrolysed starch
but not casein. Its genomic G+C content was 50.3 mol%. Its major fatty acids were
anteiso-C15 : 0, C16 : 0, and iso-C16 : 0. Phylogenetic analysis, based on the
16S rRNA gene sequences, showed that KUDC6143T belonged to the genus
Paenibacillus, with the most closely related type strain being Paenibacillus
pinihumi S23T (97.8 %). Based on its phenotypic characteristics, phylogenetic
data and genetic data, strain KUDC6143T should be considered as representing a
novel species of the genus Paenibacillus, for which we propose the name
Paenibacillus elymi sp. nov. The type strain is KUDC6143T (=KCTC 33853T=DSM
106581T).
PMID- 29957169
TI - Symbiotic and non-symbiotic Paraburkholderia isolated from South African Lebeckia
ambigua root nodules and the description of Paraburkholderia fynbosensis sp. nov.
AB - Nine Gram-negative, rod-shaped bacteria were isolated from Lebeckia ambigua root
nodules. All strains were able to nodulate and fix nitrogen with Lebeckia ambigua
apart from WSM4178T, WSM4181 and WSM4182. Based on the 16S rRNA gene phylogeny,
all strains were closely related to Paraburkholderia species (98.4-99.9 %),
belonging to the Betaproteobacteria class and Burkholderiaceae family. According
to 16S rRNA gene phylogeny the closest relative for WSM4174-WSM4177 and WSM4179
WSM4180 was Paraburkholderia tuberum(99.80-99.86 %), for WSM4178T was
Paraburkholderia caledonica (98.42 %) and for WSM4181-WSM4182 was
Paraburkholderia graminis (99.79 %). Analysis of the gyrB and recA housekeeping
genes supported the assignment of WSM4181-WSM4182 to P. graminis and the other
investigated strains could be assigned to the genus Paraburkholderia. The results
of DNA-DNA hybridization, physiological and biochemical tests allowed genotypic
and phenotypic differentiation of WSM4178T from the closest validly published
Paraburkholderia species. However, WSM4174-WSM4177 and WSM4179-WSM4180 could not
reliably be distinguished from its closest neighbour and therefore complete
genome comparison was performed between WSM4176 and P. tuberum STM678T which gave
ANI values of 96-97 %. Chemotaxonomic data, including fatty acid profiles and
quinone data supported the assignment of the strains to the genus
Paraburkholderia. On the basis of genotypic and phenotypic data one novel
species, Paraburkholderiafynbosensis sp. nov. (WSM4178T=LMG 27177T=HAMBI 3356T),
is proposed and the isolation of P. tuberum and P. graminis from root nodules of
Lebeckia ambigua is reported.
PMID- 29957170
TI - A novel regulatory factor affecting the transcription of methionine biosynthesis
genes in Escherichia coli experiencing sustained nitrogen starvation.
AB - The initial adaptive transcriptional response to nitrogen (N) starvation in
Escherichia coli involves large-scale alterations to the transcriptome mediated
by the transcriptional activator, NtrC. One of these NtrC-activated genes is
yeaG, which encodes a conserved bacterial kinase. Although it is known that YeaG
is required for optimal survival under sustained N starvation, the molecular
basis by which YeaG benefits N starved E. coli remains elusive. By combining
transcriptomics with targeted metabolomics analyses, we demonstrate that the
methionine biosynthesis pathway becomes transcriptionally dysregulated in
DeltayeaG bacteria experiencing sustained N starvation. It appears the ability of
MetJ, the master transcriptional repressor of methionine biosynthesis genes, to
effectively repress transcription of genes under its control is compromised in
DeltayeaG bacteria under sustained N starvation, resulting in transcriptional
derepression of MetJ-regulated genes. Although the aberrant biosynthesis does not
appear to be a contributing factor for the compromised viability of DeltayeaG
bacteria experiencing sustained N starvation, this study identifies YeaG as a
novel regulatory factor in E. coli affecting the transcription of methionine
biosynthesis genes under sustained N starvation.
PMID- 29957171
TI - Edaphobacter flagellatus sp. nov. and Edaphobacter bradus sp. nov., two
acidobacteria isolated from forest soil.
AB - Two aerobic and obligately acidophilic bacteria, designated HZ411T and 4MSH08T,
were isolated from the forest soil of Dinghushan Biosphere Reserve, Guangdong
Province, PR China (23 degrees 10' N, 112 degrees 31' E). These two strains
were Gram-stain-negative short rods that multiplied by binary division. HZ411T
was motile, with a single polar flagellum, but 4MSH08T was non-motile. The
results of the 16S rRNA gene sequence analysis indicated that these two strains
formed a common clade with members of the genusEdaphobacterin subdivision 1 of
the phylum Acidobacteria but they each occupied a unique position in the genus.
HZ411T and 4MSH08T had a 16S rRNA gene sequence similarity of 96.2 % between each
other and the highest sequence similarity of 97.7 and 96.9 % to Edaphobacter
modestusJbg-1T and Edaphobacter aggregansWbg-1T, respectively. The DNA-DNA
hybridization rate between HZ411T and E. modestusJbg-1T was 22.7 %. The DNA G+C
contents of HZ411T and 4MSH08T were 57.7 and 59.3 %, respectively. HZ411T and
4MSH08T had similar major (>10 %) fatty acids with very high percentages of iso
C15 : 0 and C16 : 1omega7c, and similar major polar lipid profiles (both
contained a phosphatidylethanolamine, phosphatidyldimethylethanolamine and
glycolipid and several unidentified aminolipids and polar lipids). On the basis
of these physiological, phylogenetic and chemotaxonomic data, we suggest that
HZ411T and 4MSH08T represent two novel species of the genus Edaphobacter, for
which the names Edaphobacter flagellatus HZ411T (=GDMCC 1.1193=LMG 30085) and
Edaphobacter bradus 4MSH08T (=GDMCC 1.1317=KCTC 62475) are proposed.
PMID- 29957173
TI - Piscinibacter caeni sp. nov., isolated from activated sludge.
AB - A yellowish-pigmented bacterial strain, designated as MQ-18T, was isolated from a
sample of activated sludge collected from a pharmaceutical factory in Zhejiang,
China. The strain was characterized through a polyphasic taxonomy approach. 16S
rRNA gene sequence analysis demonstrated that strain MQ-18T showed high
similarities to Piscinibacter defluvii SH-1T (99.7 %) and Piscinibacter aquaticus
IMCC1728T (98.4 %), thereby suggesting that it belongs to the genus
Piscinibacter. The DNA-DNA relatedness values of this strain to strains SH-1T and
IMCC1728T were only 35.4 and 33.3 %, respectively. Cells of MQ-18T were Gram
negative, aerobic, motile, rod-shaped and non-spore forming. This strain
exhibited growth at 25-37 degrees C (optimum: 30 degrees C) in the presence of
0-3.0 % (w/v) NaCl (optimum, 0 % NaCl) and at pH 5.0-8.0 (pH 7.0). The
predominant fatty acids were C12 : 0 (5.5 %), C16 : 0 (33.7 %), summed feature 3
(C16 : 1omega7c and/or C16 : 1omega6c; 38.5 %), and summed feature 4 (anteiso-C17
: 1 B and/or iso C17 : 1 I; 11.6 %). The main quinone type was ubiquinone-8, and
the major polyamines were cadaverine and putrescine. The major polar lipid
profile consisted of diphosphatidylglycerol, phosphatidylglycerol and
phosphatidylethanolamine. The DNA G+C content was 70.1 mol%. On the basis of its
phylogenetic, phenotypic and physiological characteristics, strain MQ-18T is
considered to represent a novel species of the genus Piscinibacter, for which the
name Piscinibacter caeni sp. nov. is proposed. The type strain is MQ-18T (CCTCC
AB 2017223T=JCM 32138T).
PMID- 29957172
TI - ASC acts in a caspase-1-independent manner to worsen acute pneumonia caused by
Pseudomonas aeruginosa.
AB - PURPOSE: Pseudomonas aeruginosa expresses a type III secretion system (T3SS) that
activates the host inflammasome-mediated immune response. We examined the role of
inflammasome activation in severe infection outcomes. METHODS: We infected
C57BL/6 (B6) mice lacking inflammasome components ASC or caspase-1/11 with a
highly virulent strain of P. aeruginosa, PSE9, using a mouse model of pneumonia.
We evaluated inflammasome activation in vitro by infecting bone marrow-derived
macrophages (BMDMs) with PSE9 and measuring cell death and release of
inflammasome-dependent cytokines IL-18 and IL-1beta. A bioluminescent reporter
assay was used to detect activity of caspase-1 and caspase-3/7 in BMDMs from B6
and ASC-deficient mice.Results/Key Findings. ASC-/- mice exhibited significantly
improved survival relative to caspase-1/11-/- mice and B6 mice, demonstrating
that ASC and caspase-1/11 play differential roles in P. aeruginosa infection. We
found that ASC-/- BMDMs exhibited significantly reduced cell death relative to B6
BMDMs, while caspase-1/11-/- BMDMs were resistant to cell death. IL-18 and IL
1beta were both detected from supernatants of infected B6 BMDMs, but cytokine
release was abrogated in both ASC-/- and caspase-1/11-/- BMDMs. We detected a 2.5
fold increase in the activation of caspase-3/7 in PSE9-infected B6 BMDMs, but no
increase in infected ASC-/- BMDMs. Cell death, cytokine release and caspase-3/7
activity were dependent on a functional T3SS. CONCLUSIONS: Collectively, these
results are consistent with a model whereby the T3SS apparatus of P. aeruginosa
activates the caspase-1-dependent inflammasome and caspase-3/7 through an ASC
dependent mechanism. This activation may have implications for the outcomes of P.
aeruginosa infections.
PMID- 29957174
TI - Rhodococcus electrodiphilus sp. nov., a marine electro active actinobacterium
isolated from coral reef.
AB - An electrogenic bacterium was isolated from a marine coral, designated as strain
JC435T and its taxonomic status examined by using a polyphasic approach. Results
from the 16S rRNA gene sequence study showed that the isolate belonged to the
genus Rhodococcus and formed a cluster with Rhodococcus ruber KCTC 9806T (99.5 %
16S rRNA gene sequence similarity) and Rhodococcus aetherivorans JCM 14343T (99.3
%), respectively. Genome relatedness based on DNA-DNA hybridization to the type
strains of closest-related species was less than 30 % and the DeltaTm of >7
degrees C, suggesting that strain represents a new species of the genus
Rhodococcus. The major fatty acids were C16 : 0, C18 : 1omega9c, C18 : 010-methyl
and C16 : 1omega6c and/or C16 : 1omega7c. The polar lipids of strain JC435T were
diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
phosphatidylinositol mannoside, phosphatidylinositol, three unknown phospholipids
and an unknown amino lipid. The major isoprenoid quinone was MK-8(H2), with 8 %
of MK-7(H2) and 2 % of MK-9(H2) as minor components. Whole-cell hydrolysates
contained meso-diaminopimelic acid, arabinose and galactose as the diagnostic
diamino acid and sugars. Mycolic acids were detected. The genomic DNA G+C content
of strain JC435T was 69.8 mol%. On the basis of phylogenetic genotypic,
physiological and chemotaxonomic analysis, strain JC435T is considered to
represent a novel species of the genus Rhodococcus for which the name
Rhodococcuselectrodiphilus sp. nov. is proposed. The type strain is JC435T (=KCTC
39856T=LMG 29881T=MCC 3659T).
PMID- 29957175
TI - Antimicrobial resistance profiles of Shigella dysenteriae isolated from
travellers returning to the UK, 2004-2017.
AB - PURPOSE: Antimicrobial resistance (AMR) profiles of 754 strains of Shigella
dysenteriae isolated between 2004 and 2017 from UK travellers reporting symptoms
of gastrointestinal (GI) disease were reviewed to look for evidence of emerging
AMR associated with travellers' diarrhoea. METHODOLOGY: A travel history was
provided for 72.7 % (548/754) of cases, of which 90.9 % (498/548) reported travel
outside the UK within 7 days of onset of symptoms, and 9.1 % (50/498) reported no
travel in that time frame. During the course of this study, whole genome
sequencing (WGS) was implemented for GI disease surveillance, and we compared
phenotypic AMR profiles with those derived from WGS data (n=133).Results/Key
findings. The phenotypic and genotypic AMR results correlated well, with 90.1 %
(121/133) isolates having concordant results to 10 classes of antimicrobials.
Resistance to the first-line drugs commonly used in the treatment of shigellosis
was observed throughout the study (ampicillin, 54.1%; chloramphenicol, 33.7 %;
sulphonamides, 76.0 %; trimethoprim, 80.0%). Between 2004 and 2017, resistance to
all classes of antimicrobials (except the phenicols) increased. The proportion of
isolates exhibiting reduced susceptibility to ciprofloxacin increased from 3.8 %
in 2004 to 75.7 % in 2017, and this was significantly associated with cases
reporting travel to Asia compared to Africa (P<0.001). Of the 201 sequenced
isolates, 3.0 % (20/201) had either blaCTX-M-15 or blaCMY-4. CONCLUSIONS:
Increasing MDR, along with resistance to the fluroquinolones and the third
generation cephalosporins, in Shigella dysenteriae causing travellers' diarrhoea
provides further evidence for the need to regulatethe use of antimicrobial agents
and continuous monitoring of emerging AMR.
PMID- 29957176
TI - Corrigendum: Molecular characterization of serogroup 19 Streptococcus pneumoniae
in the Czech Republic in the post-vaccine era.
PMID- 29957178
TI - Predictive regulation and human design.
AB - Organisms evolving toward greater complexity were selected across aeons to use
energy and resources efficiently. Efficiency depended on prediction at every
stage: first a clock to predict the planet's statistical regularities; then a
brain to predict bodily needs and compute commands that dynamically adjust the
flows of energy and nutrients. Predictive regulation (allostasis) frugally
matches resources to needs and thus forms a core principle of our design. Humans,
reaching a pinnacle of cognitive complexity, eventually produced a device (the
steam engine) that converted thermal energy to work and were suddenly awash in
resources. Today boundless consumption in many nations challenges all our
regulatory mechanisms, causing obesity, diabetes, drug addiction and their
sequelae. So far we have sought technical solutions, such as drugs, to treat
complex circuits for metabolism, appetites and mood. Here I argue for a different
approach which starts by asking: why does our regulatory system, which evolution
tuned for small satisfactions, now constantly demand 'more'?
PMID- 29957179
TI - Correction: Lovastatin fails to improve motor performance and survival in methyl
CpG-binding protein2-null mice.
PMID- 29957177
TI - Epidermal LysM receptor ensures robust symbiotic signalling in Lotus japonicus.
AB - Recognition of Nod factors by LysM receptors is crucial for nitrogen-fixing
symbiosis in most legumes. The large families of LysM receptors in legumes
suggest concerted functions, yet only NFR1 and NFR5 and their closest homologs
are known to be required. Here we show that an epidermal LysM receptor (NFRe),
ensures robust signalling in L. japonicus. Mutants of Nfre react to Nod factors
with increased calcium spiking interval, reduced transcriptional response and
fewer nodules in the presence of rhizobia. NFRe has an active kinase capable of
phosphorylating NFR5, which in turn, controls NFRe downstream signalling. Our
findings provide evidence for a more complex Nod factor signalling mechanism than
previously anticipated. The spatio-temporal interplay between Nfre and Nfr1, and
their divergent signalling through distinct kinases suggests the presence of an
NFRe-mediated idling state keeping the epidermal cells of the expanding root
system attuned to rhizobia.
PMID- 29957180
TI - Division of labor in bacteria.
AB - The emergence of subpopulations that perform distinct metabolic roles has been
observed in populations of genetically identical bacteria.
PMID- 29957181
TI - Dentistry at a crossroads.
PMID- 29957182
TI - Letters.
PMID- 29957183
TI - Author's response.
PMID- 29957184
TI - Correction.
PMID- 29957186
TI - Should I be calling in sick?: Some ethical considerations on self-care.
PMID- 29957185
TI - Periodontitis in US Adults: National Health and Nutrition Examination Survey 2009
2014.
AB - BACKGROUND: This report presents weighted average estimates of the prevalence of
periodontitis in the adult US population during the 6 years 2009-2014 and
highlights key findings of a national periodontitis surveillance project.
METHODS: Estimates were derived for dentate adults 30 years or older from the
civilian noninstitutionalized population whose periodontitis status was assessed
by means of a full-mouth periodontal examination at 6 sites per tooth on all non
third molar teeth. Results are reported according to a standard format by
applying the Centers for Disease Control and Prevention/American Academy of
Periodontology periodontitis case definitions for surveillance, as well as
various thresholds of clinical attachment loss and periodontal probing depth.
RESULTS: An estimated 42% of dentate US adults 30 years or older had
periodontitis, with 7.8% having severe periodontitis. Overall, 3.3% of all
periodontally probed sites (9.1% of all teeth) had periodontal probing depth of 4
millimeters or greater, and 19.0% of sites (37.1% of teeth) had clinical
attachment loss of 3 mm or greater. Severe periodontitis was most prevalent among
adults 65 years or older, Mexican Americans, non-Hispanic blacks, and smokers.
CONCLUSIONS: This nationally representative study shows that periodontitis is a
highly prevalent oral disease among US adults. PRACTICAL IMPLICATIONS: Dental
practitioners should be aware of the high prevalence of periodontitis in US
adults and may provide preventive care and counselling for periodontitis. General
dentists who encounter patients with periodontitis may refer these patients to
see a periodontist for specialty care.
PMID- 29957187
TI - Keeping an eye on your gums.
PMID- 29957188
TI - Comparative study of acute and mid-term complications with leadless and
transvenous cardiac pacemakers.
AB - BACKGROUND: Leadless cardiac pacemakers (LCPs) aim to mitigate lead- and pocket
related complications seen with transvenous pacemakers (TVPs). OBJECTIVE: The
purpose of this study was to compare complications between the LCP cohort from
the LEADLESS Pacemaker IDE Study (Leadless II) trial and a propensity score
matched real-world TVP cohort. METHODS: The multicenter LEADLESS II trial
evaluated the safety and efficacy of the Nanostim LCP (Abbott, Abbott Park, IL)
using structured follow-up, with serious adverse device effects independently
adjudicated. TVP data were obtained from Truven Health MarketScan claims
databases for patients implanted with single-chamber TVPs between April 1, 2010
and March 31, 2014 and more than 1 year of preimplant enrollment data.
Comorbidities and complications were identified via International Classification
of Diseases, Ninth Revision and Current Procedural Terminology codes. Short-term
(<=1 months) and mid-term (>1-18 months) complications were compared between the
LCP cohort and a propensity score-matched subset of the TVP cohort. RESULTS:
Among 718 patients with LCPs (mean age 75.6 +/- 11.9 years; 62% men) and 1436
patients with TVPs (mean age 76.1 +/- 12.3 years; 63% men), patients with LCPs
experienced fewer complications (hazard ratio 0.44; 95% confidence interval 0.32
0.60; P < .001), including short-term (5.8% vs 9.4%; P = .01) and mid-term (0.56%
vs 4.9%; P < .001) events. In the short-term time frame, patients with LCPs had
more pericardial effusions (1.53% vs 0.35%; P = .005); similar rates of vascular
events (1.11% vs 0.42%; P = .085), dislodgments (0.97% vs 1.39%; P = .54), and
generator complications (0.70% vs 0.28%; P = .17); and no thoracic trauma
compared to patients with TVPs (rate of thoracic trauma 3.27%). In short- and mid
term time frames, TVP events absent from the LCP group included lead-related,
pocket-related, and infectious complications. CONCLUSION: Patients with LCPs
experienced fewer overall short- and mid-term complications, including infectious
and lead- and pocket-related events, but more pericardial effusions, which were
uncommon but serious.
PMID- 29957189
TI - A change from atrial fibrillation into a wide QRS tachycardia in a 69-year-old
man.
PMID- 29957190
TI - Our Professional Staff-Celebrating a Century of the AAOMS.
PMID- 29957191
TI - Advances in Imaging Over 100 Years: The Impact on Oral and Maxillofacial Surgery.
PMID- 29957192
TI - Validation of Exercise Capacity as a Surrogate Endpoint in Exercise-Based
Rehabilitation for Heart Failure: A Meta-Analysis of Randomized Controlled
Trials.
AB - OBJECTIVES: This study sought to validate exercise capacity (EC) as a surrogate
for mortality, hospitalization, and health-related quality of life (HRQOL).
BACKGROUND: EC is often used as a primary outcome in exercise-based cardiac
rehabilitation (CR) trials of heart failure (HF) via direct cardiorespiratory
assessment of maximum oxygen uptake (Vo2peak) or through submaximal tests, such
as the 6-min walk test (6MWT). METHODS: After a systematic review, 31 randomized
trials of exercise-based CR compared with no exercise control (4,784 HF patients)
were included. Outcomes were pooled using random effects meta-analyses, and
inverse variance weighted linear regression equations were fitted to estimate the
relationship between the CR on EC and all-cause mortality, hospitalization, and
HRQOL. Spearman correlation coefficient (rho), R2 at trial level, and surrogate
threshold effect (STE) were calculated. STE represents the intercept of the
prediction band of the regression line with null effect on the final outcome.
RESULTS: Exercise-based CR is associated with positive effects on EC measured
through Vo2peak (+3.10 ml/kg/min; 95% confidence interval [CI]: 2.01 to 4.20) or
6MWT (+41.15 m; 95% CI: 16.68 to 65.63) compared to control. The analyses showed
a low level of association between improvements in EC (Vo2peak or 6MWT) and
mortality and hospitalization. Moderate levels of correlation between EC with
HRQOL were seen (e.g., R2 <52%; |rho| < 0.72). Estimated STE was an increase of 5
ml/kg/min for Vo2peak and 80 m for 6MWT to predict a significant improvement in
HRQOL. CONCLUSIONS: The study results indicate that EC is a poor surrogate
endpoint for mortality and hospitalization but has moderate validity as a
surrogate for HRQOL. Further research is needed to confirm these findings across
other HF interventions.
PMID- 29957193
TI - What Is Your Quest?
PMID- 29957195
TI - Cardiovascular Drug Pricing: Less Innovation for More Access?
PMID- 29957194
TI - The Hospital Readmissions Reduction Program: Evidence for Harm.
PMID- 29957196
TI - Finding a Balance Between Quality and Quantity of Data in Acute Heart Failure.
PMID- 29957197
TI - Reply: Finding a Balance Between Quality and Quantity of Data in Acute Heart
Failure.
PMID- 29957198
TI - Correction.
PMID- 29957199
TI - Mitotic live-cell imaging at different timescales.
AB - Mitosis is a highly dynamic and choreographed process in which chromosomes are
captured by the mitotic spindle and physically segregated into the two daughter
cells to ensure faithful transmission of the genetic material. Live-cell
fluorescence microscopy enables these dynamics to be analyzed over diverse
temporal scales. Here we present the methodologies to study chromosome
segregation at three timescales: we first show how automated tracking of
kinetochores enables investigation of mitotic spindle and chromosome dynamics in
the seconds-to-minutes timescale; next we highlight how new DNA live dyes allow
the study of chromosome segregation over a period of several hours in any cell
line; finally, we demonstrate how image sequences acquired over several days can
reveal the fate of whole cell populations over several consecutive cell
divisions.
PMID- 29957200
TI - Choosing the right microscope to image mitosis in zebrafish embryos: A practical
guide.
AB - Tissue growth and organismal development require orchestrated cell proliferation.
To understand how cell division guides development, it is important to explore
mitosis at the tissue-wide, cellular, and subcellular scale. At the tissue level
this includes determining a tissue's mitotic index, at the cellular level the
tracing of cell lineages, and at the subcellular level the characterization of
intracellular components. These different tasks can be addressed by different
imaging approaches (e.g., laser-scanning confocal, spinning disk confocal, and
light-sheet fluorescence microscopy). Here, we summarize three protocols for
exploring different facets of mitosis in developing zebrafish embryos. Zebrafish
embryos are transparent and their rapid external development greatly facilitates
the study of cellular processes and developmental dynamics using microscopy. A
critical step in all imaging studies of mitosis in development is to choose the
most suitable microscope for each scientific question. This choice is important
in order to ensure a balance between the required temporal and spatial resolution
and minimal phototoxicity that could otherwise perturb the process of interest.
The use of different microscopy techniques, best suited for the purpose of each
experiment, thus permits to generate a comprehensive and unbiased view on how
mitosis influences development.
PMID- 29957201
TI - Advanced microscopy methods for bioimaging of mitotic microtubules in plants.
AB - Mitotic cell division in plants is a dynamic process playing a key role in plant
morphogenesis, growth, and development. Since progress of mitosis is highly
sensitive to external stresses, documentation of mitotic cell division in living
plants requires fast and gentle live-cell imaging microscopy methods and suitable
sample preparation procedures. This chapter describes, both theoretically and
practically, currently used advanced microscopy methods for the live-cell
visualization of the entire process of plant mitosis. These methods include
microscopy modalities based on spinning disk, Airyscan confocal laser scanning,
structured illumination, and light-sheet bioimaging of tissues or whole plant
organs with diverse spatiotemporal resolution. Examples are provided from studies
of mitotic cell division using microtubule molecular markers in the model plant
Arabidopsis thaliana, and from deep imaging of mitotic microtubules in robust
plant samples, such as legume crop species Medicago sativa.
PMID- 29957202
TI - Microsurgery and microinjection techniques in mitosis research.
AB - The use of microtechnique for studying cell division is well established (Begg &
Ellis, 1979; Wadsworth, 1999; Zhang & Nicklas, 1999). The advantage of
microinjection in cell division research is the timed delivery of a
macromolecules at a particular stage of mitosis (for example, pre- vs
postanaphase), which can circumvent the spindle assembly checkpoint (Hinchcliffe
et al., 2016). Micromanipulation can be used to remove whole organelles, such as
the centrosome or nucleus and examine the effects on cell division (Hinchcliffe
et al., 2001; Hornick et al., 2011). The focus of this chapter is on methods for
microinjection and micromanipulation of cultured mammalian cells. We describe
pulling and shaping microneedles, as well as the imaging chambers we use. We also
provide information on cell culture conditions, and imaging techniques used for
our long-term observation studies, which allow cells to be followed on the order
of several days.
PMID- 29957203
TI - Analyzing the micromechanics of the cell division apparatus.
AB - Cell division involves mechanical processes, such as chromosome transport and
centrosome separation. Quantitative micromanipulation-based approaches have been
central to dissecting the forces driving these processes. We highlight two
biophysical assays that can be employed for such analyses. First, an in vitro
"mini-spindle" assay is described that can be used to examine the collective
mechanics of mitotic motor proteins cross-linking two microtubules. In the
spindle, motor proteins (e.g., kinesin-5, kinesin-14, and dynein) can localize to
overlapping microtubules that slide relative to each other, work as an ensemble,
and equilibrate between cytoplasm and the microtubules. The "mini-spindle" assay
can recapitulate these features and allows measurements of forces generated
between adjacent microtubules and their dependence on filament orientation,
sliding speed, overlap length, and motor protein density. Second, we describe a
force-calibrated microneedle-based "whole-spindle" micromechanics assay.
Microneedle-based micromanipulation can be a useful technique to examine cellular
scale mechanics, but its use has been restricted by the difficulty in getting
probes to penetrate the plasma membrane without disrupting cell physiology. As
detailed here, the use of cell-free extracts prepared from metaphase-arrested
Xenopus eggs can address this limitation. These micromanipulation studies also
benefit from the use of frozen stocks of Xenopus egg extract. Together, these
approaches can be used to decipher how micromechanics and biochemical activities
ensure successful cell division.
PMID- 29957204
TI - Optogenetic reversible knocksideways, laser ablation, and photoactivation on the
mitotic spindle in human cells.
AB - At the onset of mitosis, cells assemble the mitotic spindle, a dynamic
micromachine made of microtubules and associated proteins. Although most of these
proteins have been identified, it is still unknown how their collective behavior
drives spindle formation and function. Over the last decade, RNA interference has
been the main tool for revealing the role of spindle proteins. However, the
effects of this method are evident only after a longer time period, leading to
difficulties in the interpretation of phenotypes. Optogenetics is a novel
technology that enables fast, reversible, and precise control of protein activity
by utilization of light. In this chapter, we present an optogenetic knocksideways
method for rapid and reversible translocation of proteins from the mitotic
spindle to mitochondria using blue light. Furthermore, we discuss other optical
approaches, such as laser ablation of microtubule bundles in the spindle and
creation of reference marks on the bundles by photoactivation of photoactivatable
GFP. Finally, we show how different optical perturbations can be combined in
order to acquire deeper understanding of the mechanics of mitosis.
PMID- 29957205
TI - Live imaging of C. elegans oocytes and early embryos.
AB - Caenorhabditis elegans is a self-fertilizing hermaphroditic worm. A single C.
elegans worm therefore produces both male and female gametes that fuse to
generate embryos. While sperm production stops at the end of the C. elegans
larval development, oocytes are continuously generated and fertilized during the
entire reproductive life of the adult worm. The molecular and cellular mechanisms
involved in gametogenesis and the early embryonic divisions are highly conserved
between worms and humans; thus C. elegans is a powerful model to study meiotic
and mitotic cell divisions in a metazoan system. Additionally, the optical
transparency of the worm combined with the ease of the genome-editing methods can
be used to easily follow the subcellular behavior of any fluorescently tagged
protein of interest using light microscopy approaches. Here we describe two
methods for preparing live samples to study oocyte meiotic and early embryonic
mitotic divisions by confocal microscopy in C. elegans.
PMID- 29957206
TI - Combining microscopy and biochemistry to study meiotic spindle assembly in
Drosophila oocytes.
AB - Studies using Drosophila have played pivotal roles in advancing our understanding
of molecular mechanisms of mitosis throughout the past decades, due to the short
generation time and advanced genetic research of this organism. Drosophila is
also an excellent model to study female meiosis in oocytes. Pathways such as the
acentrosomal assembly of the meiotic spindle in oocytes are conserved from fly to
humans. Collecting and manipulating large Drosophila oocytes for microscopy and
biochemistry are both time and cost efficient, offering advantages over mouse or
human oocytes. Therefore, Drosophila oocytes serve as an excellent platform for
molecular studies of female meiosis using a combination of genetics, microscopy,
and biochemistry. Here we describe key methods to observe the formation of the
meiotic spindle either in fixed or in live oocytes. Moreover, biochemical methods
are described to identify protein-protein interactions in vivo.
PMID- 29957208
TI - Live-cell microscopy of meiosis in spermatocytes.
AB - For the analysis of the molecular mechanisms underlying mammalian meiosis, the
establishment of a transient gene expression system for meiocytes has been long
awaited. We have established an efficient in vivo electroporation method for live
mouse testis and demonstrate short-term transgene expression in spermatocytes. By
expressing specific marker proteins fused with GFP, this technique is applicable
not only to fixed cell observations after transgene expression but also to live
imaging to dissect dynamic cellular events in live spermatocytes. The protocol is
also adapted to the dissection of mutant phenotypes with defective chromosome
movement during meiotic prophase I, as well as a phenotype rescue assay by
expressing functional cDNAs in mutant testes.
PMID- 29957207
TI - Methods to study meiosis in insect spermatocytes.
AB - This chapter covers methods that are useful for the in vitro culture and live
cell study of insect spermatocytes in general and of crane-fly spermatocytes in
particular. The merits of crane-fly spermatocytes are detailed in the
Introduction section. In the following sections, step-by-step instructions are
given for optimizing visualization of meiotic events taking place within living
spermatocytes by employing microaspiration to flatten cells and then in
subsequent operations to manipulate them via microinjection. Emphasis is on the
attributes of ionophoretic injection as a way of introducing fluorescently
conjugated proteins into the cytoplasm of flattened spermatocytes. In the last
section of this chapter, the presentation of pressure injection is an alternative
for delivering cell permeable probes into the interstitial space surrounding
spermatocytes within in vitro preparations.
PMID- 29957209
TI - Live imaging of cell division in preimplantation mouse embryos using inverted
light-sheet microscopy.
AB - Systematic studies of cell divisions at the beginning of mammalian life are of
fundamental importance for our understanding of embryonic development and
fertility. However, in the past the challenges of in vitro embryo culture and the
embryo's pronounced light sensitivity have precluded a detailed investigation of
preimplantation cell divisions. This protocol is based on recent technological
breakthroughs in inverted light microscopy tailored for mouse embryology. Due to
its reduced light dose, and therefore low phototoxicity, as well as higher
acquisition speed, light-sheet microscopy allows extended 3D time-lapse imaging
of early embryonic development with very high spatial and temporal resolution.
This imaging approach enables imaging of key subcellular structures during the
critical cell cycles from the zygote up to the blastocyst stage, with a
resolution that allows automatic computational tracking and quantitative analysis
of the dynamics of mitotic organelles.
PMID- 29957210
TI - Correlating light microscopy with serial block face scanning electron microscopy
to study mitotic spindle architecture.
AB - The mitotic spindle is a complex structure that coordinates the accurate
segregation of chromosomes during cell division. To understand how the mitotic
spindle operates at the molecular level, high resolution imaging is needed.
Serial block face-scanning electron microscopy (SBF-SEM) is a technique that can
be used to visualize the ultrastructure of entire cells, including components of
the mitotic spindle such as microtubules, kinetochores, centrosomes, and
chromosomes. Although transmission electron microscopy (TEM) has higher
resolution, the reconstruction of large volumes using TEM and tomography is labor
intensive, whereas SBF-SEM takes only days to process, image, and segment
samples. SBF-SEM fills the resolution gap between light microscopy (LM) and TEM.
When combined with LM, SBF-SEM provides a platform where dynamic cellular events
can be selected and imaged at high resolution. Here we outline methods to use
correlation and SBF-SEM to study mitotic spindle architecture in 3D with high
resolution.
PMID- 29957211
TI - Correlated light and electron microscopy of cell division in large marine
oocytes, eggs, and embryos.
AB - The rapid and synchronous divisions of large and transparent oocytes, eggs, and
embryos of marine species are exceptionally well suited for microscopic
observation. Consequently, these cells have been models for cell division
research since its beginnings and contributed some of its first and most
fundamental discoveries. While large size and rapid transitions render these
cells ideal specimens for light microscopy, the same features constitute a
challenge for electron microscopy. Here, we describe example protocols from our
work on starfish oocyte meiosis, where we overcome these challenges by using live
imaging of fluorescently labeled structures in combination with correlated
electron microscopy. In this work, we demonstrate how: (i) to capture a rapid,
transient event in time and (ii) to localize a small structure within the large
oocyte. These techniques are applicable with minor modifications to oocytes and
embryos of other species and, possibly, to other cell types.
PMID- 29957212
TI - A microscopy-based approach for studying meiosis in live and fixed human oocytes.
AB - Human eggs frequently carry an incorrect number of chromosomes, which is a
leading cause of pregnancy loss and congenital disorders. The origins of high
aneuploidy rates in human eggs have remained largely unclear. This is due to two
main reasons: first, the availability of human eggs is limited so that studies of
fixed human eggs typically involve very small numbers and limited
quantifications. Second, methods for studying meiosis in live human eggs have
been missing. The ever rising prevalence of Assisted Reproductive Technologies
has facilitated a recent breakthrough in the field. The mechanistic basis of
meiosis in humans can now be examined directly in live eggs. Here, we present a
robust method for culturing human eggs in vitro and describe how meiotic
processes in human eggs can be studied in real time using fluorescent reporters.
We further describe methods for the in-depth analysis of immunolabeled eggs by
super-resolution light microscopy.
PMID- 29957213
TI - Superresolution imaging of the synaptonemal complex.
AB - This chapter describes how two different superresolution microscopy techniques,
namely, structured illumination microscopy and direct stochastic optical
reconstruction microscopy, can be used to analyze the molecular architecture of
the synaptonemal complex. The experimental protocols provided allow the
construction of precise localization maps for different synaptonemal complex
proteins.
PMID- 29957214
TI - Cryo-electron tomography of SYCP3 fibers under native conditions.
AB - The synaptonemal complex (SC) forms during the early stages of meiotic prophase
I, when it mediates the pairing of homologous chromosomes. Despite the crucial
role of the SC in chromosome synapsis and genetic recombination, the molecular
details of its function are still unclear. High-resolution information on the
structure of SC proteins would be very valuable to elucidate the molecular basis
of their function in meiosis. Here we show how cryo-electron tomography and
subtomographic averaging can be usefully applied to provide insights into the
structure of the helical SYCP3 protein in its filamentous state. The
establishment of such method should prove of use for structural studies of other
SC proteins, such as SYCP1 and the TEX12-SYCE2 complex, which can form
physiologically relevant filamentous assemblies, and ultimately for the
structural analysis of the SC.
PMID- 29957215
TI - Quantification of three-dimensional spindle architecture.
AB - Mitotic and meiotic spindles are microtubule-based structures to faithfully
segregate chromosomes. Electron tomography is currently the method of choice to
analyze the three-dimensional (3D) architecture of both types of spindles. Over
the years, we have developed methods and software for automatic segmentation and
stitching of microtubules in serial sections for large-scale reconstructions. 3D
reconstruction of microtubules, however, is only the first step toward biological
insight. The second step is the analysis of the structural data to derive
measurable spindle properties. Here, we present a comprehensive set of techniques
to quantify spindle parameters. These techniques provide quantitative analyses of
specific microtubule classes and are applicable to a variety of tomographic
reconstructions of spindles from different organisms.
PMID- 29957216
TI - Quantitative live and super-resolution microscopy of mitotic chromosomes.
PMID- 29957217
TI - Live imaging of cell division in 3D stem-cell organoid cultures.
AB - Examining cell behavior in its correct tissue context is a major challenge in
cell biology. The recent development of mammalian stem cell-based organoid
cultures offers exciting opportunities to visualize dynamic cellular events in a
3D tissue-like setting. We describe here an approach for live imaging of cell
division processes in intestinal organoid cultures derived from human and mouse
adult stem cells. These approaches can be extended to the analysis of cellular
events in diseased tissue, such as patient-derived tumor organoids.
PMID- 29957218
TI - Preface.
PMID- 29957219
TI - Acute Cardiac Effects of Severe Pre-Eclampsia.
AB - BACKGROUND: Pre-eclampsia with severe features (PEC) is a pregnancy-specific
syndrome characterized by severe hypertension and end-organ dysfunction, and is
associated with short-term adverse cardiovascular events, including heart
failure, pulmonary edema, and stroke. OBJECTIVES: The authors aimed to
characterize the short-term echocardiographic, clinical, and laboratory changes
in women with PEC, focusing on right ventricular (RV) systolic pressure (RVSP)
and echocardiographic-derived diastolic, systolic, and speckle tracking
parameters. METHODS: In this prospective observational study, the authors
recruited 63 women with PEC and 36 pregnant control patients. RESULTS: The PEC
cohort had higher RVSP (31.0 +/- 7.9 mm Hg vs. 22.5 +/- 6.1 mm Hg; p < 0.001) and
decreased global RV longitudinal systolic strain (RVLSS) (-19.6 +/- 3.2% vs.
23.8 +/- 2.9% [p < 0.0001]) when compared with the control cohort. For left-sided
cardiac parameters, there were differences (p < 0.001) in mitral septal e'
velocity (9.6 +/- 2.4 cm/s vs. 11.6 +/- 1.9 cm/s), septal E/e' ratio (10.8 +/-
2.8 vs. 7.4 +/- 1.6), left atrial area size (20.1 +/- 3.8 cm2 vs. 17.3 +/- 2.9
cm2), and posterior and septal wall thickness (median [interquartile range]: 1.0
cm [0.9 to 1.1 cm] vs. 0.8 cm [0.7 to 0.9 cm], and 1.0 cm [0.8 to 1.2 cm] vs. 0.8
cm [0.7 to 0.9 cm]). Eight women (12.7%) with PEC had grade II diastolic
dysfunction, and 6 women (9.5%) had peripartum pulmonary edema. CONCLUSIONS:
Women with PEC have higher RVSP, higher rates of abnormal diastolic function,
decreased global RVLSS, increased left-sided chamber remodeling, and higher rates
of peripartum pulmonary edema, when compared with healthy pregnant women.
PMID- 29957220
TI - Pre-Eclampsia: A Twilight Zone Between Health and Cardiovascular Disease?
PMID- 29957221
TI - Anti-Inflammatory Effects on Atherosclerotic Lesions Induced by CXCR4-Directed
Endoradiotherapy.
PMID- 29957222
TI - There Is a Place for Digoxin: We Think So!
PMID- 29957223
TI - Reference for Serum Digoxin Concentration Should Be Redefined Now.
PMID- 29957224
TI - Reply: Digoxin Use in Atrial Fibrillation: Minimizing and Refining its Use When
Still Needed.
PMID- 29957225
TI - Digital Defenses for Hacked Hearts: Why Software Patching Can Save Lives.
PMID- 29957226
TI - Reply: Cyberattacks and Cardiac Devices: Firmware Patches Are Not Vaccinations!
PMID- 29957227
TI - Risk of Myocardial Infarction in Anticoagulated Patients With Atrial
Fibrillation.
AB - BACKGROUND: Evidence is conflicting as to the efficacy of direct oral
anticoagulation (DOAC) and vitamin K antagonist (VKA) for prevention of
myocardial infarction (MI). OBJECTIVES: This study aimed to investigate the risk
of MI associated with the use of apixaban, dabigatran, rivaroxaban, and VKA in
patients with atrial fibrillation. METHODS: Patients with atrial fibrillation
were identified using Danish health care registers and stratified by initial oral
anticoagulant treatment. Standardized absolute 1-year risks were estimated based
on Cox regression for hazard rates of MI hospitalizations and mortality. Reported
were absolute risks separately for the oral anticoagulation treatments and
standardized to the characteristics of the study population. RESULTS: Of the
31,739 patients included (median age, 74 years; 47% females), the standardized 1
year risk of MI for VKA was 1.6% (95% confidence interval [CI]: 1.3 to 1.8),
apixaban was 1.2% (95% CI: 0.9 to 1.4), dabigatran was 1.2% (95% CI: 1.0 to 1.5),
and rivaroxaban was 1.1% (95% CI: 0.8 to 1.3). No significant risk differences
were observed in the standardized 1-year risks of MI among the DOACs: dabigatran
versus apixaban (0.04%; 95% CI: -0.3 to 0.4), rivaroxaban versus apixaban (0.1%;
95% CI: -0.4 to 0.3), and rivaroxaban versus dabigatran (-0.1%; 95% CI: -0.5 to
0.2). The risk differences for DOACs versus VKA were all significant: -0.4% (95%
CI: -0.7 to -0.1) for apixaban, -0.4% (95% CI: -0.7 to -0.03) for dabigatran, and
-0.5% (95% CI: -0.8 to -0.2) for rivaroxaban. CONCLUSIONS: No significant risk
differences of MI were found in the direct comparisons of DOACs, and DOACs were
all associated with a significant risk reduction of MI compared with VKA.
PMID- 29957228
TI - Direct Oral Anticoagulants and Myocardial Infarction: The Dust Is Settling.
PMID- 29957230
TI - Adding Troponin to the Puzzle of Heart Failure With Preserved Ejection Fraction:
Marker or Mediator?
PMID- 29957229
TI - Myocardial Injury and Cardiac Reserve in Patients With Heart Failure and
Preserved Ejection Fraction.
AB - BACKGROUND: Cardiac reserve is depressed in patients with heart failure and
preserved ejection fraction (HFpEF). The mechanisms causing this are poorly
understood. OBJECTIVES: The authors hypothesized that myocardial injury might
contribute to the hemodynamic derangements and cardiac reserve limitations that
are present in HFpEF. Markers of cardiomyocyte injury, central hemodynamics,
ventricular function, and determinants of cardiac oxygen supply-demand balance
were measured. METHODS: Subjects with HFpEF (n = 38) and control subjects without
heart failure (n = 20) underwent cardiac catheterization, echocardiography, and
expired gas analysis at rest and during exercise. Central venous blood was
sampled to measure plasma high-sensitivity troponin T levels as an index of
cardiomyocyte injury. RESULTS: Compared with control subjects, troponins were
more than 2-fold higher in subjects with HFpEF at rest and during exercise (p <
0.0001). Troponin levels were directly correlated with left ventricular (LV)
filling pressures (r = 0.52; p < 0.0001) and diastolic dysfunction (r = -0.43; p
= 0.002). Although myocardial oxygen demand was similar, myocardial oxygen supply
was depressed in HFpEF, particularly during exercise (coronary perfusion pressure
time integral; 44 +/- 9 mm Hg * s * min-1 * l * dl-1 vs. 30 +/- 9 mm Hg * s * min
1 * l * dl-1; p < 0.0001), and reduced indices of supply were correlated with
greater myocyte injury during exercise (r = -0.44; p = 0.0008). Elevation in
troponin with exercise was directly correlated with an inability to augment LV
diastolic (r = -0.40; p = 0.02) and systolic reserve (r = -0.57; p = 0.0003),
greater increases in LV filling pressures (r = 0.55; p < 0.0001), blunted cardiac
output response (r = -0.44; p = 0.002), and more severely depressed aerobic
capacity in HFpEF. CONCLUSIONS: Limitations in LV functional reserve and the
hemodynamic derangements that develop secondary to these limitations during
exercise in HFpEF are correlated with the severity of cardiac injury, assessed by
plasma levels of troponin T. Further study is warranted to determine the
mechanisms causing myocyte injury in HFpEF and the potential role of ischemia,
and to identify and test novel interventions targeted to these mechanisms. (EXEC
[Study of Exercise and Heart Function in Patients With Heart Failure and
Pulmonary Vascular Disease]; NCT01418248).
PMID- 29957231
TI - Macrophage CD31 Signaling in Dissecting Aortic Aneurysm.
AB - BACKGROUND: The authors recently found that a CD31 agonist peptide reaches
macrophages in injured aortas and exerts beneficial effects on apolipoprotein E
knockout (Apo E-/-) mice subjected to angiotensin (Ang) II infusion, a model of
experimental acute aortic dissection and intramural hematoma (ADIM). OBJECTIVES:
The purpose of this study was to evaluate the therapeutic potential of a drug
suitable agonist peptide in experimental ADIM. METHODS: P8RI, a retro-inverso
sequence of the best candidate identified by functional in vitro screening of a
peptide library, passed an absorption, distribution, metabolism, excretion and
toxicology analysis. Apo E-/- mice (male, 28-week-old) implanted with Ang II
releasing pumps received P8RI (2.5 mg/kg/day) or vehicle from day 14 (n =
10/group). Leukocytes were analyzed by flow cytometry. Healing features of human
and mouse dissected aortic segments were assessed by histology and
immunofluorescence. The effect of CD31 on macrophages was evaluated using cells
from CD31-/- mice and P8RI, in vitro. RESULTS: Human and experimental ADIM were
characterized by the infiltration of proinflammatory macrophages. The absence of
CD31 enhanced the proinflammatory polarization of macrophages, whereas the CD31
agonist P8RI favored reparative macrophages both in vitro and in vivo. The
administration of P8RI after the occurrence of ADIM prevented aneurysmal
transformation by promoting the resolution of intramural hematoma and the
production of collagen in dissected aortas in vivo, associated with enrichment of
M2 macrophages at the site of injury. CONCLUSIONS: CD31 signaling promotes the
switching of proinflammatory macrophages to the reparative phenotype and favors
the healing of experimental dissected aortas. Treatment with a drug-suitable CD31
agonist may facilitate the clinical management of ADIM.
PMID- 29957232
TI - Biologically-Based Therapies for Aortic Diseases: Why the Long Lag in
Translation?
PMID- 29957234
TI - CRISPRed Cardiomyocytes to Decrypt Variants of Uncertain Significance.
PMID- 29957233
TI - Genome Editing of Induced Pluripotent Stem Cells to Decipher Cardiac
Channelopathy Variant.
AB - BACKGROUND: The long QT syndrome (LQTS) is an arrhythmogenic disorder of QT
interval prolongation that predisposes patients to life-threatening ventricular
arrhythmias such as Torsades de pointes and sudden cardiac death. Clinical
genetic testing has emerged as the standard of care to identify genetic variants
in patients suspected of having LQTS. However, these results are often confounded
by the discovery of variants of uncertain significance (VUS), for which there is
insufficient evidence of pathogenicity. OBJECTIVES: The purpose of this study was
to demonstrate that genome editing of patient-specific induced pluripotent stem
cells (iPSCs) can be a valuable approach to delineate the pathogenicity of VUS in
cardiac channelopathy. METHODS: Peripheral blood mononuclear cells were isolated
from a carrier with a novel missense variant (T983I) in the KCNH2 (LQT2) gene and
an unrelated healthy control subject. iPSCs were generated using an integration
free Sendai virus and differentiated to iPSC-derived cardiomyocytes (CMs).
RESULTS: Whole-cell patch clamp recordings revealed significant prolongation of
the action potential duration (APD) and reduced rapidly activating delayed
rectifier K+ current (IKr) density in VUS iPSC-CMs compared with healthy control
iPSC-CMs. ICA-105574, a potent IKr activator, enhanced IKr magnitude and restored
normal action potential duration in VUS iPSC-CMs. Notably, VUS iPSC-CMs exhibited
greater propensity to proarrhythmia than healthy control cells in response to
high-risk torsadogenic drugs (dofetilide, ibutilide, and azimilide), suggesting a
compromised repolarization reserve. Finally, the selective correction of the
causal variant in iPSC-CMs using CRISPR/Cas9 gene editing (isogenic control)
normalized the aberrant cellular phenotype, whereas the introduction of the
homozygous variant in healthy control cells recapitulated hallmark features of
the LQTS disorder. CONCLUSIONS: The results suggest that the KCNH2T983I VUS may
be classified as potentially pathogenic.
PMID- 29957235
TI - Cardiovascular Diseases in India Compared With the United States.
AB - This review describes trends in the burden of cardiovascular diseases (CVDs) and
risk factors in India compared with the United States; provides potential
explanations for these differences; and describes strategies to improve
cardiovascular health behaviors, systems, and policies in India. The prevalence
of CVD in India has risen over the past 2 decades due to population growth,
aging, and a stable age-adjusted CVD mortality rate. Over the same time period,
the United States has experienced an overall decline in age-adjusted CVD
mortality, although the trend has begun to plateau. These improvements in CVD
mortality in the United States are largely due to favorable population-level risk
factor trends, specifically with regard to tobacco use, cholesterol, and blood
pressure, although improvements in secondary prevention and acute care have also
contributed. To realize similar gains in reducing premature death and disability
from CVD, India needs to implement population-level policies while strengthening
and integrating its local, regional, and national health systems. Achieving
universal health coverage that includes financial risk protection should remain a
goal to help all Indians realize their right to health.
PMID- 29957237
TI - Is Preoperative Maintenance of the Curve of Spee Associated With an Increase of
Facial Height in Class II Short Face Orthognathic Patients? A Never Answered
Dogmatic Question.
AB - PURPOSE: To determine the association of maintaining the curve of Spee (COS)
before surgery with post-treatment facial height in patients with Class II short
face syndrome undergoing combined orthodontic and orthognathic treatment.
MATERIALS AND METHODS: In this retrospective cohort study, the clinical and
radiologic data of all patients with Class II short face syndrome who underwent
combined orthodontic and orthognathic treatment were reviewed. The primary
outcome variables were 1) preoperative COS and 2) post-treatment facial height.
Depth of the COS and skeletal and soft tissue relations were measured on digital
lateral cephalometric radiographs. Descriptive and bivariate statistics were
performed. RESULTS: The sample was composed of 20 patients. Statistical analysis
showed a significant increase of soft tissue facial height after treatment (P <
.02). Preoperative depth of the COS was significantly associated with changes in
sagittal skeletal relations (angle formed by the sella, nasion, and B point
[SNB], correlation [cor] = -0.54, P < .02; angle formed by the A point, nasion,
and B point [ANB], cor = 0.43, P < .06). These changes and changes in overjet
were associated with the post-treatment increase of lower facial height (SNB, cor
= 0.70, P < .001; ANB, cor = -0.69, P < .001; overjet, cor = -0.55, P < .049).
The ratios of upper to lower soft tissue facial height and upper to lower lip
height were improved to near normal values (1.0 and 0.5, respectively) for most
patients. CONCLUSION: In patients with Class II short face orthognathism, the
present study found that maintaining the COS before surgery was associated with
1) an increase of soft tissue facial height and 2) an improvement of the ratio of
upper to lower facial height and the ratio of upper to lower lip height to near
normal values. Moreover, the depth of the COS was correlated with the post
treatment increase of facial height through changes in skeletal relations and was
related to the degree of severity of the mandibular deficiency.
PMID- 29957236
TI - The Role of Nutraceuticals in Statin Intolerant Patients.
AB - Statins are the most common drugs administered for patients with cardiovascular
disease. However, due to statin-associated muscle symptoms, adherence to statin
therapy is challenging in clinical practice. Certain nutraceuticals, such as red
yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and
stanols alone or in combination with each other, as well as with ezetimibe, might
be considered as an alternative or add-on therapy to statins, although there is
still insufficient evidence available with respect to long-term safety and
effectiveness on cardiovascular disease prevention and treatment. These
nutraceuticals could exert significant lipid-lowering activity and might present
multiple non-lipid-lowering actions, including improvement of endothelial
dysfunction and arterial stiffness, as well as anti-inflammatory and
antioxidative properties. The aim of this expert opinion paper is to provide the
first attempt at recommendation on the management of statin intolerance through
the use of nutraceuticals with particular attention on those with effective low
density lipoprotein cholesterol reduction.
PMID- 29957238
TI - In reply.
PMID- 29957239
TI - Remembering an Icon in Office Anesthesia.
PMID- 29957240
TI - Implant-Supported Hybrid Prosthesis for Severe Mandibular Defects: A Sequence of
Treatments From Alveolar Distraction Osteogenesis to Implant Restoration.
AB - PURPOSE: Although a variety of treatment methodologies for the physiological
reconstruction of mandibular defects exist, the use of these methods has often
been fragmented and has focused on partial effects of therapy. This article
describes a sequence of treatments for a severe mandibular defect. PATIENTS AND
METHODS: Two patients with severe hard and soft tissue defects had physiological
function restored in 4 steps, including alveolar distraction osteogenesis,
implant insertion based on a prosthesis, application of dermal matrix membrane in
reconstruction of attachment gingiva, and the use of a hybrid prosthesis designed
via computer-aided design and computer-aided manufacturing, to produce an
adequate bone tissue volume, an adequate amount of attached gingiva, and a
reliable prosthesis. RESULTS: The sequence of treatments successfully achieved
physiological reconstruction. Biological complications around the implants and
mechanical complications in the implants or prostheses did not occur within a 4
year follow-up period. CONCLUSIONS: On the basis of the current 4-year follow-up,
this study shows that a treatment sequence can be predictable and effective for
severe mandibular defects, which suggests that it could be considered a potential
protocol for patients with severe mandibular defects.
PMID- 29957241
TI - Does Mandibular Distraction Change the Laryngoscopy Grade in Infants With Robin
Sequence?
AB - PURPOSE: To review a series of infants with Robin sequence (RS) who underwent
mandibular distraction osteogenesis (MDO) at the authors' institution and
document changes in pre- and postoperative laryngoscopy grades. MATERIALS AND
METHODS: Consecutive patients with RS who underwent MDO from March 2005 to June
2017 were identified. Patients were included if they had a preoperative
polysomnogram confirming obstructive sleep apnea, had failed nonoperative airway
management, had undergone MDO by the senior author (C.M.R.), and had complete
documentation. Patients were excluded if they did not have a laryngoscopy
performed (ie, tracheostomy dependent) or if there was insufficient information
in their medical record. Variables included demographic data, operative
information, and laryngoscopic details at 3 time points: before MDO (T0), at
device removal (T1), and at latest follow-up laryngoscopy (T2). Descriptive
statistics were computed. Significance was set at a P value less than .05.
RESULTS: Twenty-two infants with RS underwent MDO during the study period and 13
of these met criteria for inclusion. Mean age at MDO (T0) was 19.6 +/- 38.8
weeks. Mean ages at device removal (T1) and latest follow-up laryngoscopy (T2)
were 28.2 +/- 41.5 and 62.7 +/- 49.6 weeks, respectively. Three patients had
Stickler syndrome; the others had nonsyndromic RS. Mean apnea-hypopnea index was
23.6 +/- 16.6 preoperatively and 0.3 +/- 0.7 after MDO (P = .011). At T0, a grade
IIb laryngoscopic view was most common (46.1%) and only 3 patients (23.1%) had a
grade I view. At T1, most patients (69.2%) had a grade I view and only 2 (14.4%)
had a grade of IIb or worse (P = .011). At T2, all but 1 patient had a grade I
view. CONCLUSION: In addition to resolving obstructive apnea, MDO is associated
with an improvement in the grade of laryngoscopic view. This could increase
airway safety at home and improve ease of intubation for future operations.
PMID- 29957242
TI - Laser-Assisted Indocyanine Green Imaging for Assessment of Perioperative
Maxillary Perfusion During Le Fort I Osteotomy: A Pilot Study.
AB - PURPOSE: To determine the changes in maxillary perfusion during different stages
of Le Fort I osteotomies as measured by laser-assisted indocyanine green imaging
(LAICGI) and to determine whether various clinical factors affect maxillary
vascular perfusion. MATERIALS AND METHODS: The medical records of those who had
undergone Le Fort I osteotomy with LAICGI at the University of Illinois from 2016
to 2017 were reviewed retrospectively. The maxillary perfusion levels using
LAICGI were measured before induction, after induction, after down fracture,
after segmentalization (for segmental osteotomies), and after wound closure. The
effects of clinical variables, including gender, race, American Society of
Anesthesiologists physical status, type of Le Fort I osteotomy, intraoperative
status of the descending palatine vessels, maxillary movements (anteroposterior,
vertical, transverse), and hemodynamic data (mean arterial blood pressure, heart
rate), were analyzed. RESULTS: Compared with the preoperative baseline values,
the indocyanine green (ICG) levels decreased after down fracture and
mobilization, segmentalization, and wound closure; no statistically significant
differences were found among these 3 points. Segmentalization did not affect the
ICG levels compared with the nonsegmentalized cases. Male gender and the amount
of maxillary impaction were significantly associated statistically with decreased
ICG levels, although the difference was not clinically significant. CONCLUSIONS:
Compared with the baseline levels, maxillary perfusion, as measured by LAICGI,
decreased from down fracture to wound closure. Segmentalization did not appear to
influence maxillary perfusion, although male gender and impaction were associated
with decreased perfusion. Because of its safety and convenience, LAICGI shows
promise as a method of assessing maxillary perfusion in future largescale
prospective studies linking perioperative perfusion to the occurrence of aseptic
necrosis.
PMID- 29957243
TI - Morphologic dysplasia in Myelodysplastic Syndromes: How accurate are
morphologists?
PMID- 29957244
TI - Corrigendum.
PMID- 29957245
TI - Hypoglycaemia in patients with cystic fibrosis- harbinger of poor outcomes or
innocent bystander?
PMID- 29957246
TI - Cognitive profile of children with sickle cell anemia compared to healthy
controls.
AB - OBJECTIVE: To evaluate the cognitive abilities of children and adolescents with
sickle cell anemia diagnosed through neonatal screening and to compare them with
healthy controls, adjusting the results to their socioeconomic status. METHODS:
Cognitive assessment was performed with the Wechsler WISC-III scale in 64
children and adolescents with sickle cell anemia and in 64 controls matched by
gender and age, without the disease and without neurological impairment;
socioeconomic status was measured by the Criterion Brasil. RESULTS: All cognitive
scores were lower in the group of patients. The mean overall IQ, Verbal IQ, and
Performance IQ were, respectively, 90.95 for the group of patients and 113.97 for
the controls (p<0.001); 91.41 for the group of patients and 112.31 for the
controls (p<0.001); 92.34 for the group of patients and 113.38 for the controls
(p<0.001). Scores for processing speed, distraction resistance, and perceptual
organization were also significantly lower in patients. A direct and significant
correlation was detected between socioeconomic status and cognitive scores. In
the multivariate analysis, for the same socioeconomic status, a child with sickle
cell anemia had an average IQ of 21.2 points lower than the mean IQ observed for
the controls (p<0.001), indicating that the disease, adjusted for the
socioeconomic effect, is a strong predictor of the overall IQ. CONCLUSION: The
cognitive impairment of children with sickle cell anemia is severe and manifests
even when the disease effect is adjusted to the socioeconomic status. In the
authors' view, such impairment requires an early preventive approach in order to
avoid this cognitive damage.
PMID- 29957247
TI - Left ventricular assessment in patients with mucopolysaccharidosis using
conventional echocardiography and myocardial deformation by two-dimensional
speckle-tracking method.
AB - OBJECTIVE: Mucopolysaccharidosis is a rare genetic disease characterized by the
intralysosomal deposition of glycosaminoglycans. Cardiovascular impairment is a
common feature. Cardiac signs and symptoms are underestimated due to the disease
involvement in other organs. Enzyme replacement therapy can be used in
mucopolysaccharidosis I, II, IV, and VI. Thus, the knowledge about the use of new
echocardiography tools is relevant to improve the care of this population. This
study aimed to describe left ventricular function assessment by conventional
echocardiography and left ventricular global longitudinal strain analysis and
compare the alterations in patients receiving enzyme replacement therapy and who
had different ages at the start of therapy. METHOD: Outpatient-based descriptive
study. The patients were submitted to conventional echocardiography and left
ventricular global longitudinal strain measurement. RESULTS: Sixteen patients
were evaluated; median age of 14.2 years (SD=5.2 years). Left ventricular
hypertrophy was found in nine patients (56.2%). All patients had preserved left
ventricular systolic function (Simpson and Teichholz). Nine (56.2%) patients
showed alterations in left ventricular global longitudinal strain. The study
showed a positive association between left ventricular hypertrophy and alteration
in the left ventricular global longitudinal strain, and late start of enzyme
replacement therapy and alteration in the left ventricular global longitudinal
strain. CONCLUSION: Echocardiographic alterations in patients with
mucopolysaccharidosis were frequently observed, especially alterations in the
left ventricular geometry and subclinical dysfunction. Patients who had a late
enzyme replacement therapy start showed an association with worse left
ventricular global longitudinal strain values, reinforcing the need for early
diagnosis and treatment. The use of new echocardiographic tools may improve the
follow-up of these patients.
PMID- 29957248
TI - Health self-perception and its association with physical activity and nutritional
status in adolescents.
AB - OBJECTIVE: To evaluate the association between total physical activities,
physical activity in free time and nutritional status with self-perceived health
in adolescents of both genders. METHODS: This is a quantitative study that
integrates the school-based, cross-sectional epidemiological survey with
statewide coverage, whose sample consisted of 6261 adolescents (14-19 years old)
selected by random conglomerate sampling. Data were collected using the Global
School-based Student Health Survey. The chi-squared test (chi2) and the Poisson
regression model with robust variance were used in the data analyses. RESULTS: It
was observed that 27.3% of the adolescents had a negative health self-perception,
which was higher among girls (33.0% vs. 19.0%, p<0.001). After adjusting for
potential confounding factors, it was observed that boys who did not practice
physical activity during free time (PR=1.44, 95% CI: 1.15-1.81) and were
classified as insufficiently active (PR=1.27, 95% CI: 1.04-1.56), as well as
girls who did not practice physical activity during free time (PR=1.15, 95% CI:
1.02-1.29) and were classified as overweight (PR=1.27, 95% CI: 1.01-1.29) had a
greater chance of negative health self-perception. CONCLUSION: Behavioral issues
may have different effects on health self-perception when comparing boys with
girls. Negative health self-perception was associated with nutritional status in
girls and a lower level of physical activity in boys, and the practice of
physical activity in the free time was considered a protective factor against a
negative health self-perception for adolescents of both genders.
PMID- 29957249
TI - Health-related quality of life in adolescents with excess weight.
AB - OBJECTIVE: To identify health-related quality of life in adolescents with excess
weight and associated factors, such as gender, age, and weight categories.
METHOD: A cross-sectional study with collected and secondary data from 276
adolescents aged between 10 and 19 years with overweight and obesity, and whose
parents or guardians authorized their participation. Anthropometric data,
pubertal development, and the PedsQL 4.0 questionnaire were collected for the
health-related quality of life assessment. Categorical data were described as
numbers and percentages. For the description of health-related quality of life
subscales, medians and the 25th and 75th percentiles were used, as well as the
Mann-Whitney test for comparisons between age group, gender, and weight
categories. RESULTS: The median health-related quality of life total score was
78.3 (68.5-87.4). The lowest scale was the "emotional score", 65 (50-80). Higher
health-related quality of life was found in boys in most of the scores (p<0.05),
except for the "school score" (p=0.09). Regarding the age group, the median of
the "physical scores" (p=0.03) and "social score" (p=0.02) were significantly
lower in the group younger than 14 years. When separated according to weight
categories, it was verified that obese adolescents differed significantly in
relation to the "physical score" (p=0.00), "school score" (p=0.04), and "total
score" (p=0.02) of the health-related quality of life. However, there was no
significant difference between the emotional, social, and psychosocial scores.
CONCLUSIONS: Adolescents with overweight and obesity show losses in the health
related quality of life and also between the different domains, when separated by
age, gender, and weight categories.
PMID- 29957250
TI - Increased plasma trimethylamine-N-oxide is associated with incident atrial
fibrillation.
AB - BACKGROUND: Plasma trimethylamine-N-oxide (TMAO) is associated with
cardiovascular disease; however specific relationships with cardiac arrhythmias
are unknown. We evaluated the association between plasma TMAO and incident atrial
fibrillation (AF). METHODS: Risk associations were explored among 3797 patients
with suspected stable angina in the Western Norway Coronary Angiography Cohort
(WECAC) and verified in 3143 elderly participants in the community-based
Hordaland Health Study (HUSK). Information on endpoints was obtained from
nationwide registries. RESULTS: Median follow-up was 7.3 and 10.8 years in the
WECAC and HUSK cohorts, respectively, and 412 (10.9%) and 484 (15.4%) subjects
were registered with incident AF. The age and gender adjusted HRs were 1.16, 95%
CI 1.05-1.28 and 1.10, 95% CI 1.004-1.19 per 1 SD increase in log-transformed
plasma TMAO. Adjusting for hypertension, BMI, smoking, diabetes, or intake of
total choline, a TMAO precursor, did not materially influence the risk
associations. Among patients in WECAC, further extensive adjustment for other AF
risk factors yielded similar results. Adding TMAO to traditional AF risk factors
(age, gender, hypertension, BMI, smoking and diabetes) yielded a continuous net
reclassification improvement of 0.108, 95% CI 0.015-0.202 and 0.139, 95% CI 0.042
0.235. CONCLUSIONS: Plasma TMAO was associated with and improved reclassification
of incident AF in two independent Norwegian cohorts with long-term follow-up. The
relationship was independent of traditional AF risk factors, as well as of
dietary choline intake. Our findings motivate further studies to explore
endogenous metabolic factors influencing the relationship between TMAO and
cardiovascular disease.
PMID- 29957251
TI - Chronic kidney disease, worsening renal function and outcomes in a heart failure
community setting: A UK national study.
AB - BACKGROUND: Routine heart failure (HF) monitoring and management is in the
community but the natural course of worsening renal function (WRF) and its
influence on HF prognosis is unknown. We investigated the influence of routinely
monitored renal decline and related comorbidities on imminent hospitalisation and
death in the HF community population. METHODS: A nested case-control study within
an incident HF cohort (N = 50,114) with 12-years follow-up. WRF over 6-months
before first hospitalisation and 12-months before death was defined by >20%
reduction in estimated glomerular filtration rate (eGFR). Additive interactions
between chronic kidney disease (CKD) and comorbidities were investigated.
RESULTS: Prevalence of CKD (eGFR<60 ml/min/1.73m2) in the HF community was 63%,
which was associated with an 11% increase in hospitalisation and 17% in
mortality. Both risk associations were significantly worse in the presence of
diabetes. Compared to HF patients with eGFR,60-89, there was no or minimal
increase in risk for mild to moderate CKD (eGFR,30-59) for both outcomes.
Adjusted risk estimates for hospitalisation were increased only for severe
CKD(eGFR,15-29); Odds Ratio 1.49 (95%CI;1.36,1.62) and renal failure(eGFR,<15);
3.38(2.67,4.29). The relationship between eGFR and mortality was U-shaped; eGFR,
>=90; 1.32(1.17,1.48), eGFR,15-29; 1.68(1.58,1.79) and eGFR,<15; 3.04(2.71,3.41).
WRF is common and associated with imminent hospitalisation (1.50;1.37,1.64) and
mortality (1.92;1.79,2.06). CONCLUSIONS: In HF, the risk associated with CKD
differs between the community and the acute HF setting. In the community setting,
moderate CKD confers no risk but severe CKD, WRF or CKD with other comorbidities
identifies patients at high risk of imminent hospitalisation and death.
PMID- 29957252
TI - Patient reported outcome in HFpEF: Sex-specific differences in quality of life
and association with outcome.
AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated
with poor quality of life (QoL), or patient reported outcome (PRO). Despite
female predominance in HFpEF, sex-specific differences in PROs remain poorly
studied. We assessed PRO measures and their association with HF-severity and
outcome in HFpEF by sex. METHODS AND RESULTS: In 378 patients with HFpEF from the
KaRen study, EQ-5D-3L(r) and Minnesota Living with Heart Failure Questionnaire(r)
(MLHFQ) were assessed. Characteristics and comorbidities were largely similar in
women (n = 212, 57%) and men. Women expressed worse QoL in EQ-5D-3L(r)(EQ-VAS),
independent of age and HF-severity, mean (SD), 57 (20) vs. 61 (19), p = 0.010.
There was no difference in MLHFQ, 31 (21) vs. 29 (21), p = 0.269. Spearman's
correlations with HF-severity (NYHA-class) were for MLHFQ in women rs 0.37 vs.
men 0.41, p for both <0.001, and for EQ-VAS rs -0.28, p = 0.001 vs. -0.45, p <
0.001. Correlations with natriuretic peptides were for MLHFQ rs 0.21, p = 0.003
in women vs. men 0.27, p < 0.001, and for EQ-VAS rs -0.17 vs. -0.27, p both <
0.001. Associations between PRO and the composite of HF hospitalisation or all
cause death were present in men only, adjusted HR per 5 units increase in MLHFQ
1.06, 95% confidence interval (CI) 1.01-1.11, p = 0.02 and EQ-VAS, HR 0.93, 95%
CI 0.88-0.98, p = 0.010. CONCLUSION: In HFpEF, women had worse general but
similar disease specific QoL compared to men. QoL was more strongly associated
with HF-severity in men, and associated with outcomes only in men. In women with
HFpEF, QoL appears less determined by HF itself and potentially more by other
unknown factors.
PMID- 29957253
TI - Age at start of endurance training is associated with patterns of left
ventricular hypertrophy in middle-aged runners.
AB - BACKGROUND: Left ventricular hypertrophy (LVH) is a physiological adaptation to
long-term endurance training. We investigated the impact of age at start of
endurance training on LV geometry in a cohort of male, middle-aged, non-elite
endurance athletes. METHODS: A total of 121 healthy, normotensive, Caucasian
participants of a 10-mile race were recruited and assessed with an echocardiogram
and a comprehensive interview. Athletes were classified based on patterns of LVH.
RESULTS: Thirty-five athletes (31%) had LVH. Athletes with eccentric LVH (16%)
were significantly younger at start of endurance training compared to athletes
with concentric LVH (15%, 14 +/- 5 years vs. 31 +/- 8 years; P < 0.001). Although
the yearly volume of endurance training was comparable between athletes with
eccentric and concentric LVH, athletes with eccentric LVH had shorter race times.
All athletes with an increased LV end diastolic volume index (LVEDVI; >=74 ml/m2)
started endurance training before or at age 25. CONCLUSIONS: In our cohort of non
elite middle-aged runners, eccentric LVH was found only in athletes with an early
start of endurance training. In case of a mature starting age, endurance training
may, contrary to what is commonly assumed, also lead to concentric LVH. The
consideration of endurance training starting age may lead to a better
understanding of morphological adaptations of the heart.
PMID- 29957254
TI - Targeting HMGB1 ameliorates cardiac fibrosis through restoring TLR2-mediated
autophagy suppression in myocardial fibroblasts.
AB - BACKGROUND: Extracellular high-mobility group box 1 (HMGB1) has been identified
as playing a critical role in the pathogenesis of tissue fibrosis. However, the
underlying mechanism of its involvement in cardiac fibrosis is still not well
defined. Here, we aim to investigate whether toll-like receptor 2 (TLR2)
contributes to the extracellular HMGB1-mediated development and progression of
cardiac fibrosis. METHODS: A mouse model of cardiac fibrosis was induced by
subcutaneous injection of isoproterenol (ISO). Glycyrrhizic acid (GA), an
inhibitor of HMGB1 derived from natural products, was simultaneously administered
by intraperitoneal injection. Echocardiography, H&E and Sirius red staining were
used to evaluate cardiac function and fibrosis. The myocardial expression of
autophagy-associated proteins was examined using immunoblotting. Cardiac
fibroblasts were treated with different concentrations of HMGB1 to examine the
expression levels of alpha-SMA, collagen I and autophagy markers. Interactions of
HMGB1/TLR2 and alpha-SMA/p62 were examined by immunoprecipitation and
immunofluorescence. RESULTS: ISO-treated mice showed characteristic cardiac
fibrosis, increased expression and co-localization of HMGB1 and TLR2, as well as
impaired autophagic signals in myocardial tissues, which could be prevented by
silencing TLR2. Exogenous administration of HMGB1 blocked the autophagic flux in
fibroblasts, which caused extensive accumulation of collagen I and alpha-SMA. In
addition, cardiac fibrosis was alleviated by GA treatment through abrogating the
interaction between HMGB1 and TLR2. CONCLUSIONS: Our study suggests that the
interaction between TLR2 and HMGB1 contributes to the pathogenesis of cardiac
fibrosis via suppressing fibroblast autophagy, and that inhibiting HMGB1 with GA
provides therapeutic benefits for the treatment of fibroproliferative heart
diseases.
PMID- 29957255
TI - Clinical and coronary haemodynamic determinants of recurrent chest pain in
patients without obstructive coronary artery disease - A pilot study.
AB - BACKGROUND: Coronary haemodynamic testing frequently identifies abnormal
pathophysiological parameters in patients with angina and non-obstructed
coronaries on angiography (NoCAD) but the clinical utility of these measures has
received limited attention. OBJECTIVE: This study aims to identify the clinical
and coronary haemodynamic determinants of recurrent chest pain at one month in
patients with NoCAD. METHODS: Patients with angina, NoCAD (<50% stenosis) and
normal LV systolic function underwent invasive coronary haemodynamic testing
involving: (1) angiographic TIMI frame and opacification rate, (2) microvascular
functional measures including coronary flow reserve (CFR) and hyperaemic
microvascular resistance (HMR), (3) coronary endothelial function assessment with
low dose intracoronary acetylcholine (IC-ACh) infusions (0.18 MUg/min & 1.8
MUg/min over 2 min), and (4) Provocative spasm testing with high dose IC-ACh
boluses (25, 50 and 100 MUg). Clinical and health status were assessed at
baseline and one month. RESULTS: In the 49 NoCAD patients (78% female, mean age
of 54 +/- 11) undergoing comprehensive coronary haemodynamic testing, 33 (67%)
continued to experience chest pain at one month. Determinants of recurrent chest
pain on univariate analysis included baseline chest pain status or a HMR > 1.9.
Multivariate logistic regression analysis identified frequent angina at baseline
(OR: 68.9 [4.1, 1165.0], p = 0.003), previous unstable angina admission (OR: 43.9
[3.5, 547.9], p = 0.003) and a HMR > 1.9 (OR: 15.6 [2.1, 114.0], p = 0.007) as
independent predictors of recurrent chest pain. CONCLUSION: In this small pilot
study, an abnormal HMR was the only coronary haemodynamic parameter that was a
determinant of ongoing angina at short-term follow-up.
PMID- 29957256
TI - Reply to "Osteopontin inhibits macrophage cholesterol efflux via NF-kappaB/ABCA1
pathway".
PMID- 29957257
TI - Response to letter from Jiang: The diagnostic value of combined D-dimer with
other indicators in suspected acute aortic dissection patients.
PMID- 29957258
TI - Validation of Endoscore. Reply to Dr Barca.
PMID- 29957259
TI - Natural history and predictors of mortality of patients with Takotsubo syndrome.
AB - BACKGROUND: Takotsubo syndrome is a unique transient cardiomyopathy. The
pathogenesis, management, and long-term prognosis of Takotsubo syndrome are
incompletely understood. The study was designed to evaluate the natural history
and determinants of outcomes in patients with Takotsubo syndrome patients.
METHODS: We analyzed 265 patients in the Mayo Clinic Takotsubo syndrome registry
for clinical presentation, treatment, and long-term outcomes with a focus on
identifying prognostic factors for mortality and recurrence. RESULTS: 95% of
patients were women with a mean age of 70 +/- 11.8 years. Among 257 patients
discharged alive, there were 89 (34.6%) deaths, 18 (6.8%) non-fatal myocardial
infarction, 12 (4.7%) cerebrovascular accidents and 23 (8.9%) re-hospitalization
for heart failure over a mean follow-up of 5.8 +/- 3.6 years. Only 4 (5%)
patients died from cardiac causes. Cancer was the single leading cause of death.
Overall 1-year survival rate was 94.2%. Independent prognostic predictors of
mortality were a history of cancer (HR 2.004, 1.334-3.012, p = 0.004), physical
stress as precipitating factors (HR 1.882, 1.256-2.822, p = 0.012), history of
depression (HR 1.622, 1.085-2.425, p = 0.009) and increased age (HR 1.059, 1.037
1.081, p < 0.001) after multivariate analysis. Beta-blockers and ACE inhibitors
at discharge were not significant predictors. There were 24 (9.1%) recurrences
during follow-up, but there were no significant differences in medical therapy
compared to patients without recurrence. CONCLUSION: The high mortality rate is
related to non-cardiac co-morbidities such as cancer. Additional determinants
include physical stressors, increased age, and history of depression. Use of beta
blockers and ACE inhibitors did not affect development, prognosis or recurrence.
PMID- 29957260
TI - The risk for a first acute coronary syndrome in patients treated with different
types of antidepressants: A population based nested case-control study.
AB - BACKGROUND: Tricyclic antidepressants (TCAs) are still used in 30% of
anxiety/depression cases and have been related to increased cardiovascular risk.
Newer serotonin/norepinephrine reuptake inhibitors (SSRIs/SNRIs) safety remains
conflicting. Our aim was to assess the risk of a first acute coronary syndrome
(ACS) in patients treated by various types of antidepressants. METHODS: Study was
a retrospective nested case-control of 40-80 years old northern-Israeli members
of Clalit Health Services (CHS) during 1.1.2003-31.12.2013. Patients with severe
psychiatric, cardiac or systemic diseases, or pre-enrollment antidepressants were
excluded. Cases that had a first ACS during the study period were matched in 1:30
ratio with controls. The association between antidepressants use and ACS was
tested by adjusted multivariable conditional logistic regression. RESULTS: The
cohort included 535,315 individuals 128,550 of whom met the exclusion/inclusion
criteria. 3391 Cases with first ACS, (incidence rate of 24.6/10,000 person years)
were matched with 88,016 controls. ACS was not associated with use of either
SSRIS/SNRIS or TCAs compared with no antidepressants use. However, treatment by
SSRIS/SNRIS was associated with a 36% decreased risk ACS compared to TCAs, OR =
0. 64, 95%CI (0.43-0.95), p = 0.029. Age 40-64 years, male gender and metabolic
syndrome associated with reduced risk of ACS among SSRIS/SNRIS compared to TCAs
users. CONCLUSION: In this study of patients without prior cardiovascular disease
neither antidepressant group imposed excess risk for ACS, compared to-no
treatment. SSRIs treatment seemed safer compared to TCAs in regard of ACS. This
study probably adds to our confidence of preferring SSRIs over TCAs in patients
without prior cardiovascular disease.
PMID- 29957261
TI - A narrative overview: Have clinical trials of PCI vs medical therapy addressed
the right question?
AB - BACKGROUND: In RCTs about revascularization, the terms "coronary artery disease"
and "ischemic heart disease" are sometimes used interchangeably. This can create
confusion concerning inclusion and exclusion criteria, which may lead to
uncertain results. OBJECTIVE: Our purpose is to investigate whether the study
populations in randomized controlled trials (RCTs) which compared percutaneous
coronary revascularization to medical therapy for stable ischemic heart disease
specifically enrolled patients with demonstrable ischemia, and how many patients
were included in trials with evidence of coronary atherosclerosis but without
evidence of ischemia. METHODS: Trial published data were obtained from ACME I,
ACME II, RITA I, RITA II, MASS I, MASS II, AVERT, ACIP, COURAGE and FAME2.
Published data were used to calculate the number of patients included in the
trials with a negative stress test but significant coronary artery stenosis and
the number of patients excluded from the trials with a positive stress test or
angina, but without significant coronary artery stenosis at the time of
angiography. RESULTS: A total of 196,433 patients were screened between 1998 and
2011. Overall about 30% of patients were excluded if they did not meet the
angiographic criteria, even though the presence of inducible ischemia or angina,
and, about 20% of patients were included without inducible ischemia. CONCLUSION:
RCTs have contributed to the confusion between coronary artery disease and
ischemic heart disease. This may limit the ability to interpret the results and
apply them in practice.
PMID- 29957262
TI - Predictors of poor clinical outcomes in patients with acute myocardial infarction
and non-obstructed coronary arteries (MINOCA).
AB - OBJECTIVE: To assess the characteristics and prognosis of patients with
myocardial infarction and non-obstructed coronary arteries (MINOCA). METHODS:
MINOCA was defined as acute myocardial infarction (AMI) with angiographic
coronary stenosis <50%.Cardiomyopathies and myocarditis were - a priori -
excluded from the study. Stenoses <30% were considered normal coronary arteries
(NCA); stenoses >=30% but <50% were considered mild coronary artery disease
(MCAD). Patients were subdivided in 3 groups: I) NCA (0 vessels; stenosis <30%);
II) 1-2 vessels showing MCAD and III) MCAD in 3 vessels or the left main stem
(LMS). RESULTS: From January 2006 to December 2014, 7935 consecutive AMI patients
were entered into our institutional database;150 (2%) were diagnosed as having
MINOCA. At a median follow-up of 7.1 years the composite end-point
(cardiovascular death, AMI or acute coronary syndrome, heart failure, stroke)
occurred in 23 patients (17.4%). Survival analysis showed no differences between
NCA versus MCAD (p = 0.781). When assessed by distribution of CAD, group III had
a lower event-free survival compared to group I and group II, respectively 54 +/-
14%, 83 +/- 4% and 90 +/- 5% (p = 0.001). In a multivariate model, only 3 vessel
disease or LMS involvement (HR = 23.5, 95% CI 2.59-173.49, P = 0.001) and high C
reactive protein at hospital admission (HR = 1.47, 95% CI 1.06-2.07, P = 0.005)
were significant predictors of the study composite endpoint. CONCLUSIONS: In
patients with MINOCA, the presence of NCA or 1-2 vessel MCAD was associated with
better long-term clinical outcomes compared with patients with MCAD affecting 3
vessels or the LMS. Increased CRP concentrations on hospital admission were also
a marker of worse clinical outcome during follow-up.
PMID- 29957263
TI - Reply to: Cardiac protection by remote ischemic preconditioning in patients with
diabetes status.
PMID- 29957264
TI - Mechanical prosthetic heart valves: Quality of anticoagulation and thromboembolic
risk. The observational multicenter PLECTRUM study.
AB - BACKGROUND: Patients with a mechanical prosthetic heart valve implantation need
to be treated with a vitamin K antagonist (VKA) due to a substantially high risk
of thromboembolism. In this study we report data on patients with mechanical
heart valves (MV), with the aim of evaluating the thromboembolic risk in relation
to the type and site of implantation, quality of anticoagulation and risk factors
associated with thromboembolism. METHODS: Observational retrospective multicenter
study among Centers affiliated to the Italian Federation of Anticoagulation
Clinics (FCSA) on patients with MV implanted after 1990 and followed for the
management of anticoagulation. RESULTS: We analyzed 2357 patients with mechanical
heart valves (55.2% males), followed for 24,081 years. During the follow-up, 164
thromboembolic events (0.67/100 pt-yrs) and 243 major bleedings (1.0/100 pt-yrs)
occurred. The median Time in Therapeutic Range (TTR), calculated in all intended
INR classes, was 60% (IQR 47-74%). The rates of thrombotic events were
significantly higher in patients intended to stay at therapeutic ranges >INR 2.0
3.0. The presence of atrial fibrillation, history of thromboembolism and of
mitral prosthesis were independently associated with thromboembolism. However, a
bad quality of anticoagulation (TTR <47%, 25 degrees percentile of our
population) was not correlated with thromboembolism. CONCLUSIONS: A low rate of
bleeding and thromboembolic events in patients with mechanical heart valves were
found, despite the sub-optimal anticoagulation control. The thromboembolic risk
was not associated with the low TTR.
PMID- 29957265
TI - Remote magnetic navigation facilitates the ablations of frequent ventricular
premature complexes originating from the outflow tract and the valve annulus as
compared to manual control navigation.
AB - OBJECTIVE: The purpose of this study was to assess the role of remote magnetic
navigation (RMN) in the ablation of ventricular premature complexes (VPCs)
arising from outflow tracts (OT) and valve annuli by comparing to manual control
navigation (MCN). METHODS: A total of 152 patients with frequent VPCs were
prospectively enrolled. 64 (42%) patients underwent ablation guided by RMN. Acute
success rate was defined as the complete elimination and non-inducibility of
clinical VPCs during the procedure. RESULTS: Overall, acute success rate of RMN
group was not different from MCN group (87.5% vs 84.1%, p = 0.56). Compared to
MCN group, the fluoroscopic time of OT-VPCs ablation in the RMN group was
significantly reduced by 67% (2.9 +/- 2.3 min vs 8.9 +/- 9.7 min, p = 0.006), and
the ablation applications in successful cases were significantly reduced (11 +/-
7 vs 15 +/- 11, p = 0.018). Compared to MCN, RMN significantly decreased ablation
applications (15 +/- 9 vs 23 +/- 9, p = 0.013) in the acute success rates of
ablating VPCs of valve annulus, and has a trend of a higher success rate for VPCs
arising from tricuspid annulus (10/11 vs 7/12, p = 0.193). No complications
occurred in the RMN group. Three cases of cardiac tamponade and one case of
transient atrioventricular block occurred in the MCN group (p = 0.22). After a
mean follow up of 16.2 months, 2/56 and 3/74 patients had a recurrence of VPCs in
the RMN group and MCN group respectively (p = 0.75). CONCLUSIONS: When compared
to MCN, RMN-guided ablation for VPCs was just as effective and safe, with the
added benefit of reduced fluoroscopic time and fewer ablation applications.
PMID- 29957266
TI - Reasons for home care clients' unplanned Hospital admissions and their
associations with patient characteristics.
AB - BACKGROUND: Unplanned hospitalizations and emergency room visits occur frequently
among home care clients The aim of this study was to identify typical discharge
diagnoses and their associations with patient characteristics among a total of
6812 Finnish home care clients aged >=63 years who were hospitalized within one
year of their first home care assessment. METHODS: A register-based study based
on Resident Assessment Instrument-Home Care (RAI-HC) assessments and nationwide
hospital discharge records. The RAI-HC assessments were linked to the hospital
discharge records of the participants' first unplanned hospitalization.
Univariate and multivariable regression analyses were used to evaluate the
association of RAI-HC determinants with discharge diagnoses. RESULTS: The most
common reason for the first hospitalization was an infectious disease (21%; n =
1446). When hospitalizations were classified according to the main diagnosis,
chronic skin ulcers, functional impairment and daily urinary incontinence were
associated with hospitalization due to infectious diseases; impaired cognitive
capacity, Alzheimer's disease or other dementia and polypharmacy (protective
effect) were associated with hospitalizations due to dementia; age of >=90 years,
congestive heart failure, coronary artery disease and using >=10 drugs with
hospitalizations due to heart diseases; and moderate or strong pain with
hospitalization due to musculoskeletal disorders. Previous falls, female sex and
an earlier hip fracture were associated with injury-related hospitalizations.
Feelings of loneliness increased the odds of hospitalization due to geriatric
symptoms without a specific diagnosis. CONCLUSION: Patient characteristics and
geriatric syndromes identified using RAI-HC predict the reasons for future
hospitalizations among new home care clients.
PMID- 29957267
TI - Expressive suppression and emotional eating in older and younger adults: An
exploratory study.
AB - AIM: A clear gap exists in regard to emotional eating and the effects of affect
and expressive suppression on emotional eating among older individuals. The aim
was to compare the emotional eating patterns of younger and older individuals and
assess the role of expressive suppression in the association between affectivity
and emotional eating in each of the age groups. METHODS: Participants were 210
individuals recruited by means of a convenience sampling, which intentionally
included a wide age range, along with varied socio-economic and education levels.
Participants completed the short version of the Dutch Eating Behavior
Questionnaire, The Positive affect (PA) and Negative Affect (NA) Schedule and the
Courtauld emotional control scale. Data was analyzed for three age groups - young
adults (aged 20-40), middle-aged adults (aged 41-60) and older adults (aged 61
87). RESULTS: Emotional eating was present among all three age groups, but it
gradually decreased with age. The use of expressive suppression increased with
age. Levels of PA and NA did not differ across the age groups and were not
associated with emotional eating, but expressive suppression predicted higher
emotional eating. The association between expressive suppression and emotional
eating was moderated by age: with a stronger association for the younger group, a
moderate association for the middle-aged group and no association for the older
adults. CONCLUSIONS: Emotional eating is present among older adults, although in
lower intensity than younger individuals, and should be identified and treated by
health and mental health practitioners.
PMID- 29957268
TI - Differential clinical features of patients with clinically amyopathic
dermatomyositis who have circulating anti-MDA5 autoantibodies with or without
myositis-associated autoantibodies.
AB - BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies
have been identified as myositis-specific autoantibodies that are often
associated with clinically amyopathic dermatomyositis (CADM) and a poor prognosis
due to rapidly progressive interstitial lung disease (RP-ILD) in East Asian
patients. Besides anti-MDA5 autoantibodies, patients with CADM may have myositis
associated autoantibodies (MAAs), which characterize other connective tissue
diseases such as rheumatoid arthritis and Sjogren's syndrome. However, the
clinical significance of the coexistence of anti-MDA5 autoantibodies and MAAs in
patients with CADM remains unclear. METHODS: We retrospectively analyzed 24
patients with CADM who had anti-MDA5 autoantibodies. Their clinical phenotypes
including laboratory test results, high-resolution lung computed tomography data,
response to therapy, and prognosis were compared between those who were positive
and negative for MAAs, such as antinuclear antibody (ANA), anti-cyclic
citrullinated peptide (CCP), anti-SSA, and anti-SSB antibodies. RESULTS: Among 24
patients, 9 (37.5%) additionally had at least one of the MAAs examined in this
study: 1 patient was positive for ANA, 5 for anti-CCP, 5 for either anti-SSA or
anti-SSB, 1 for anti-cardiolipin, and 1 for anti-Scl-70. Although all anti-MDA5
positive patients with CADM had ILD, the MAA-positive patients showed a lower
risk of developing RP-ILD (p = 0.03), a more favorable response to combination
therapy of corticosteroids and immunosuppressive agents, and a lower mortality
rate than patients with no MAAs (p = 0.03). CONCLUSIONS: Our data suggest that
anti-MDA5-positive patients with CADM who also have MAAs have a better prognosis
than those without MAAs; thus, anti-MDA5 autoantibodies by themselves may not be
strong predictors of worse clinical outcomes in patients with CADM. Coexistent
MAAs could be biomarkers for a favorable prognosis in anti-MDA5-positive patients
with CADM.
PMID- 29957269
TI - Increased mortality among patients with rheumatoid arthritis and COPD: A
population-based study.
AB - OBJECTIVES: Only few studies have addressed the prognostic impact of chronic
obstructive pulmonary disease (COPD) among patients with rheumatoid arthritis
(RA), although both diseases are frequent and smoking is a shared risk factor.
The objectives of the present study were to investigate the burden of COPD among
RA patients and the subsequent mortality. METHODS: We included patients who had a
first-time diagnosis of RA in the Danish National Patient Registry between 2004
and 2016. RA patients with COPD were identified and matched with RA patients
without COPD for year of birth, gender, and age at RA diagnosis. Mortality risks
were assessed using Kaplan-Meier mortality curves. Adjusted hazard rate ratios
(aHRRs) for death were estimated using Cox regression models. RESULTS: The study
population included 31,333 individuals with RA. 3254 of those (10.4%) had a
diagnosis of COPD and were matched to 9706 RA patients without COPD. The
mortality risks in RA patients with COPD and RA patients without COPD were 4.5%
and 1.5% within 2-6 months (aHRR = 3.0, CI 2.3-3.9), and 59.3% and 39.8% within
0.5-10 years (aHRR = 2.1, CI 1.9-2.1). CONCLUSION: Mortality was significantly
increased among RA patients with COPD. The relative mortality risk remained
significantly increased throughout the course of follow up.
PMID- 29957270
TI - Collagen biomarkers and subclinical interstitial lung disease: The Multi-Ethnic
Study of Atherosclerosis.
AB - BACKGROUND: Lung fibrosis is attributed to derangements in extracellular matrix
remodeling, a process driven by collagen turnover. We examined the association of
two collagen biomarkers, carboxy-terminal telopeptide of collagen type I (ICTP)
and amino-terminal propeptide of type III procollagen (PIIINP), with subclinical
interstitial lung disease (ILD) in adults. METHODS: We performed a cross
sectional analysis of 3244 participants age 45-84 years in the Multi-Ethnic Study
of Atherosclerosis. Serum ICTP and PIIINP levels were measured at baseline by
radioimmunoassay. Subclinical ILD was defined as high attenuation areas (HAA) in
the lung fields on baseline cardiac CT scans. Interstitial lung abnormalities
(ILA) were measured in 1082 full-lung CT scans at 9.5 years median follow-up. We
used generalized linear models to examine the associations of collagen biomarkers
with HAA and ILA. RESULTS: Median (IQR) for ICTP was 3.2 MUg/L (2.6-3.9 MUg/L)
and for PIIINP was 5.3 MUg/L (4.5-6.2 MUg/L). In fully adjusted models, each SD
increment in ICTP was associated with a 1.3% increment in HAA (95% CI 0.2-2.4%, p
= 0.02) and each SD increment in PIIINP was associated with a 0.96% increment in
HAA (95% CI 0.06-1.9%, p = 0.04). There was no association between ICTP or PIIINP
and ILA. There was no evidence of effect modification by gender, race, smoking
status or eGFR. CONCLUSIONS: Higher levels of collagen biomarkers are associated
with greater HAA independent of gender, race and smoking status. This suggests
that extracellular matrix remodeling may accompany subclinical ILD prior to the
onset of clinically evident disease.
PMID- 29957271
TI - Pulmonary interstitial glycogenosis - A systematic analysis of new cases.
AB - BACKGROUND: Pulmonary interstitial glycogenosis (PIG) is a rare paediatric
interstitial lung disease of unknown cause. The diagnosis can only be made by
lung biopsy. Less than 100 cases have been reported. Clinical features, treatment
and outcomes have rarely been assessed systematically in decent cohorts of
patients. METHODS: In this retrospective multicentre study, the clinical
presentation, radiologic findings, pattern of lung biopsy, extrapulmonary
comorbidities, treatment and outcome of eleven children with PIG were collected
systematically. RESULTS: 10/11 children presented with respiratory distress
immediatly after birth and 8/11 needed invasive ventilation. In 8/11 children
extrapulmonary comorbidities were present, congenital heart defects being the
most common. 7/11 children received systemic glucocorticoids and of these four
showed a clear favorable response. During a median follow-up of 3.0 years (range
0.42-12.0) one child died, while 10 patients improved. Chest CT-scans showed
ground-glass opacities (7/10), consolidations (6/10), linear opacities (5/10) and
mosaic attenuation (4/10) without uniform pattern. Besides interstitial
thickening related to undifferentiated glycogen positive mesenchymal cells all
tissue samples showed growth abnormalities with reduced alveolarization.
CONCLUSIONS: PIG is associated with alveolar growth abnormalities and has to be
considered in all newborns with unexplained respiratory distress. Apparent
treatment benefit of glucocorticosteroids needs to be evaluated systematically.
PMID- 29957273
TI - The utility of drug reaction assessment trials for inhaled therapies in patients
with chronic lung diseases.
AB - BACKGROUND: Current guidelines recommend a Drug Reaction Assessment (DRA) before
beginning inhaled therapies to assess for bronchoconstriction and tolerability.
There is limited evidence to support this recommendation. METHODS: In this study
we aimed to establish the predictors of successful DRAs in different patient
groups using a cohort of all DRAs performed in adults between 2011 and 2016 at
the Royal Brompton Hospital. Spirometry, age, gender, height, and underlying lung
disease were recorded. A multivariable logistic regression model was constructed
to ascertain variables associated with successful DRAs. RESULTS: There were 1492
DRA trials using hypertonic saline (32%), antimicrobials (63%), or rhDNase (5%).
The majority of patients (94%, n = 1408) passed the DRA. Mean FEV1% predicted was
58.03 (SD 23.36). Female sex, type of inhaled product, and FEV1% predicted were
established as significant predictors for DRA success. An FEV1% predicted > 55%
was associated with greater probability of DRA success (Odds Ratio [OR]: 2.96
(1.80,4.86) p < 0.0001). Those receiving dry powder, inhaled antibiotics were
more likely to pass the DRA compared to nebulised antibiotics (OR: 3.99
(1.38,11.51) p = 0.01)). CONCLUSION: This study classifies distinct patient
groups with varying baseline risks which can be used to predict tolerability when
adding an inhaled product to their management plan. Some "low risk" patients may
in future be able to self-assess their tolerability for inhaled therapies at home
to avoid unneeded hospital monitoring.
PMID- 29957274
TI - EARLY versus MILD Chronic Obstructive Pulmonary Disease (COPD).
AB - Chronic Obstructive Pulmonary Disease (COPD) is very a common, with great
morbidity and mortality, disease. Since the beginning of the disease cannot be
detected with precision and by using only FEV1 to monitor the evolution of the
disease, the Natural History of COPD is rather obscure and sometimes
controversial. Therefore, the terms EARLY COPD and MILD COPD have been used
indistinguishably in the medical literature. In this review we discuss the two
terms trying to clarify some of the definition issues, starting with a synopsis
of the Naturel History of the disease. We recommend to use the term EARLY COPD
for the pre-clinical stage of the disease (stage 0) and the term MILD COPD when
the diagnosis is confirmed by spirometry and FEV1 is above 80% predicted.
However, COPD is a complex disease and spirometric evaluation alone (MILD COPD,
stage I), cannot fully describe the clinical status of the patient. We conclude
that biomarkers to detect the starting point and been able to follow the natural
history of the disease more accurately, beyond FEV, are urgently needed.
PMID- 29957275
TI - Prenatal and postnatal tobacco smoke exposure and risk of severe bronchiolitis
during infancy.
AB - BACKGROUND: Maternal prenatal smoking has adverse effects on the growing fetus
including those of respiratory nature. Although postnatal smoke exposure is a
risk factor for respiratory infections, the effects of prenatal smoking
independent of postnatal smoke exposure are less established. We hypothesized
that both maternal prenatal smoking, and postnatal smoke exposure are risk
factors for severe bronchiolitis during infancy. METHODS: We performed a case
control study of 1353 children born between 1996 and 2011 at a single teaching
hospital. Cases were admitted to the same hospital for bronchiolitis during
infancy. Maternal prenatal smoking was collected from birth records. Postnatal
smoke exposure was collected from review of electronic health records.
Multivariable logistic regression was used to evaluate the independent
associations of the two smoking variables with severe bronchiolitis. RESULTS: 6%
of cases were exposed to maternal prenatal smoking, compared with 4% of controls
(P = 0.10). Postnatal smoke exposure was present in the households of 17% of
cases compared with 3% of controls (P < 0.001). In a multivariable model with
both smoking variables and adjustment for 10 covariates, maternal prenatal
smoking was not a significant risk factor for severe bronchiolitis (adjusted OR =
1.02, 95%CI 0.56-1.84). By contrast, postnatal smoke exposure was associated with
>300% increased odds (adjusted OR 4.19, 95%CI 2.51-6.98). CONCLUSIONS: Although
maternal prenatal smoking has many known adverse effects, it was not associated
with increased odds of severe bronchiolitis in either unadjusted or multivariable
analyses. Postnatal smoke exposure was a consistently strong risk factor. Our
findings support ongoing efforts to decrease infant exposure to ambient smoke.
PMID- 29957272
TI - Macrolide therapy is associated with lower mortality in community-acquired
bacteraemic pneumonia.
AB - BACKGROUND: Community-acquired pneumonia (CAP) has a potential complication of
bacteremia. The objective of this study was to define the clinical outcomes of
patients with CAP and bacteremia treated with and without a macrolide. MATERIALS
AND METHODS: Secondary analysis of the Community-Acquired Pneumonia Organization
database of hospitalized patients with CAP. Patients with a positive blood
culture were categorized based on the presence or absence of a macrolide in their
initial antimicrobial regimen, and severity of their CAP. Outcomes included in
hospital all-cause mortality, 30-day mortality, length of stay, and time to
clinical stability. RESULTS: Among 549 patients with CAP and bacteremia, 247
(45%) were treated with a macrolide and 302 (55%) were not. The primary pathogen
was Streptococcus pneumoniae (74%). Poisson regression with robust error variance
models were used to compare the adjusted effects of each study group on the
outcomes. The unadjusted 30-day mortality was 18.4% in the macrolide group, and
29.6% in the non-macrolide group (adjusted relative risk (aRR)0.81; 95%
confidence interval (CI)0.50-1.33; P = 0.41). Unadjusted in-hospital all-cause
mortality was 7.3% in the macrolide group, and 18.9% in the non-macrolide group
(aRR 0.54, 95% CI 0.30-0.98; P = 0.043). Length of stay and time to clinical
stability were not significantly different. CONCLUSIONS: In-hospital mortality,
but not 30-day mortality, was significantly better in the macrolide group. Our
data support the use of a macrolide in hospitalized patients with CAP and
bacteraemia.
PMID- 29957276
TI - Risk factors for mortality in patients with Pseudomonas aeruginosa pneumonia:
Clinical impact of mucA gene mutation.
AB - OBJECTIVES: Pseudomonas aeruginosa frequently colonizes the lungs of chronic
obstructive pulmonary disease (COPD) patients. Mucoid conversion is a hallmark of
chronic P. aeruginosa infection, which is mediated by mucA gene mutations. The
aim of this study is to identify predictive factors for mortality and the
influence of mucA gene mutation in COPD patients with P. aeruginosa pneumonia.
METHODS: This study assessed 75 COPD patients with P. aeruginosa pneumonia at two
university hospitals. The clinical and laboratory data were collected, and the P.
aeruginosa isolates analyzed for the presence of mucA gene mutations. RESULTS:
MucA gene mutation of P. aeruginosa was an independent predictor of mortality
(odds ratio [OR] 10.43, 95% confidence interval [CI]: 1.53-70.90, p = 0.017). In
addition, the APACHE II score and C-reactive protein/Albumin (CA) ratio were
independent predictive factors for mortality (OR 1.25, 95% CI: 1.07-1.46, p =
0.004; and OR 1.06, 95% CI: 1.02-1.10, p = 0.003, respectively). The optimal
cutoff value of CA ratio for the greatest sensitivity and specificity was
calculated as 31.27 (sensitivity, 85.7%; specificity, 80.3%). CONCLUSIONS: CA
ratio and mucA gene mutation of P. aeruginosa could be used as predictors to
identify poor prognosis in COPD patients with P. aeruginosa pneumonia.
PMID- 29957277
TI - Association between serum 25-hydroxyvitamin D levels and pulmonary function,
among Korean adults, during 2010-2014, by sex, age, and body mass index.
AB - BACKGROUND: This study examined the association between serum 25-hydroxyvitamin D
(25(OH)D) and pulmonary function, among Korean adults, from 2010 to 2014.
METHODS: The data were obtained from the fifth Korea National Health and
Nutrition Examination Survey (KNHANES 5), and the first and second year (2013
2014) of KNHANES 6. The study population comprised 14,378 individuals. The
variable of interest was serum 25(OH)D, and the dependent variable, pulmonary
function. RESULTS: All people with vitamin D levels below 30 ng/ml had lower lung
functions, which was significant in lower forced expiratory volume in the first
second (FEV1) (serum 25(OH)D < 10 ng/ml, 20 to <30 ng/ml: P = .001, 10 to <20
ng/ml: P = 0) and forced vital capacity (FVC) (serum 25(OH)D level <10 ng/ml: P =
.01, 10 to < 20 ng/ml: P = .001, 20 to <30 ng/ml: P = .008). The lower the serum
25(OH)D, the lower the levels of FEV1 in men and this was significant. (serum
25(OH)D < 10 ng/ml: P = .007, 10 to <20 ng/ml: P = .002, 20 to <30 ng/ml: P =
.007). The values of FEV1 and FVC were lower in people aged 50-69 years when
vitamin D was lower than 30 ng/ml which were all significant. Among participants
with BMI values < 23 kg/m2, lower vitamin D levels were significantly associated
with lower pulmonary function. CONCLUSIONS: We found a significant association
between serum 25(OH)D and pulmonary function, and this was related to sex, age
and body mass index.
PMID- 29957278
TI - Within and between day repeatability of the incremental shuttle walking test in
patients with thoracic cancer.
AB - BACKGROUND: Breathlessness is common in patients with thoracic cancer but
difficult to manage. The Incremental Shuttle Walking Test (ISWT) can help assess
new treatments, but its repeatability has not been described in this group. AIM:
To examine within and between day repeatability of the ISWT in this setting.
METHODS: Patients with incurable thoracic cancer were recruited from outpatient
clinics at a University Hospital. Two ISWTs were completed one hour apart on two
consecutive days, with the first test for familiarization purposes only.
Repeatability of distance walked was examined using Bland and Altman plots and
assessed as the single determination (within subject) standard deviation of the
difference between tests and its 95% range. RESULTS: Forty-one patients
participated and completed all tests. Mean (SD) distance walked was 333 (134),
349 (129) and 353 (130) m over the three tests, with the mean difference
significantly different from zero between days (16 m, 95% CI 8-24 m, P = 0.043)
but not within days (5 m, 95% CI -2 to 12 m, P = 0.47). Within and between day
single determination SD and 95% ranges were 30 (-31 to 91) m and 36 (-37 to 109)
m respectively. CONCLUSIONS: These data help inform the design of studies making
use of the ISWT and the interpretation of their findings.
PMID- 29957279
TI - Chinese herbal medicine formula for acute asthma: A multi-center, randomized,
double-blind, proof-of-concept trial.
AB - BACKGROUND: Despite advances in asthma management, exacerbations constitute a
significant health economic burden. OBJECTIVE: To observe the efficacy and safety
of Chinese herbal medicine formula entitled PingchuanYiqi (PCYQ) granule, on
acute asthma and to explore its possible mechanism. MATERIALS AND METHODS: This
proof-of-concept study consisted of a randomized, double-blind, placebo
controlled trial in patients with acute asthma (n = 300). Participants with acute
mild-to-moderate asthma recruited from seven centers in China were randomly
assigned to receive PCYQ or placebo. The primary outcomes were PEF (L/min) and
total asthma symptom scores. Furthermore, a panel of cytokines including serum IL
4, IL-5, IL-6, IL-8, IL-1beta, IL-17A, IFN-alpha, IFN-beta, IFN-gamma, CRP, CCL
5, IP-10, and PGD2 levels was detected using ELISA. RESULTS: The PCYQ (n = 139)
significantly improved the morning PEF on day 4 (349.73 +/- 93.92 vs. 313.56 +/-
92.91 L/min, P = 0.004) and day 7 (360.42 +/- 94.39 vs. 329.52 +/- 95.97 L/min, P
= 0.023), and the evening PEF on day 4 (352.65 +/- 95.47 vs. 320.58 +/- 95.30
L/min, P = 0.012) and day 7 (360.42 +/- 94.39 vs. 336.86 +/- 95.59 L/min, P =
0.029) in comparison with the placebo (n = 143). The PCYQ also improved the
clinical symptoms scores and reduced the puffs of short-acting beta2-agonist (all
P < 0.05). Furthermore, the PCYQ statistically reduced IL-5, IL-8, IL-1beta and
PGD2 in serum. CONCLUSION: The PCYQ as the Chinese herbal medicine formula
significantly improves lung function and symptoms of acute asthma, and reduces
SABA dosage possibly via decrease of inflammatory biomarkers such as IL-5, IL-8,
IL-1beta and PGD2. TRIAL REGISTRATION: ISRCTN61674768 (http://www.isrctn.com/).
PMID- 29957280
TI - Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma.
AB - BACKGROUND: Several animal studies, and one inoculation study in adult asthmatics
have shown that interleukin-33 (IL-33) is a major contributor to type-2
inflammation in acute asthma. However, the link between IL-33 and type-2
inflammation has not been shown in naturally occurring asthma exacerbations.
OBJECTIVES: To determine if airway IL-33 is associated with type-2 inflammation
measured by type-2 cytokines, FeNO and sputum eosinophils in patients presenting
to the Emergency Department with an asthma exacerbations. METHODS: Adult patients
hospitalized due to acute asthma were enrolled. Upper airways were sampled with
nasal swabs and lower airways with induced sputum. Cytokines were measured at
protein level using a Luminex(r) assay and mRNA expression level using droplet
digital-PCR. Airway sampling was repeated four weeks after exacerbation. RESULTS:
At the time of exacerbation, upper airway IL-33 correlated with upper airway IL-5
and IL-13 (R = 0.84, p < 0.01 and R = 0.76, p < 0.01, respectively) and with
lower airway IL-13 (R = 0.49, p = 0.03). Similar associations were observed for
mRNA expression. Lower airway IL-33 positively correlated with lower airway IL-13
(R = 0.84, p < 0.01). IL-13 and IL-33 were positively correlated with FeNO, and
IL-5 with eosinophils. The association between IL-33 and type-2 cytokines were
still present four weeks after exacerbation. CONCLUSION: This is the first study
to demonstrate that airway IL-33 is associated with type-2 cytokines in naturally
occurring asthma exacerbations in adults, providing in vivo evidence supporting
that IL-33 may be driving type-2 inflammation in acute asthma. Thus supporting IL
33 as a potential future drug target due to its role, upstream in the
immunological cascade.
PMID- 29957281
TI - Nationwide use of theophylline among adults-A 20-year Danish drug utilisation
study.
AB - BACKGROUND: Theophylline, a dimethylxanthine, has been used the last 100 years to
treat airway disease. Although it is one of the most widely prescribed medicines
to treat asthma and chronic obstructive pulmonary disease (COPD) throughout the
years, the utilisation patterns are not well-described. METHODS: Using the Danish
Register of Medicinal Products Statistics, we identified adults above 18 years
redeeming one or more prescriptions of theophylline between 1997 up to 2017, with
a 2-year run-in period from 1995 to 1997. Using descriptive statistics, we
reported the development in prevalence, incidence, and a measure of treatment
duration (proportion of patients covered). RESULTS: In total, 55,636 individuals
redeemed 1,066,475 prescriptions of theophylline, 30,619 women (55%) and 25,017
men (45%). The prevalence decreased from 401 per 100,000 individuals in 1997 to
26 per 100,000 individuals in 2016. The incidence rate decreased throughout the
entire study period (105 per 100,000 person-years in 1997 to 5 per 100,000 person
years in 2016). In total, 52% were still current users three months after
theophylline initiation, 33%, 27%, and 23% were current users after 6 months, one
year, and two years. CONCLUSIONS: Although newer and more efficient medicines to
treat asthma and COPD has been developed, theophylline is still prescribed and
used in 2016, but the incidence and prevalence have decreased markedly since
1997.
PMID- 29957282
TI - Acute respiratory events in patients with bronchiectasis-COPD overlap syndrome: A
population-based cohort study.
AB - BACKGROUND: The clinical phenotypes of chronic obstructive pulmonary disease
(COPD) are related to various outcomes. We investigated the risk of acute
respiratory events in patients with bronchiectasis-COPD overlap syndrome (BCOS)
in Taiwan. METHODS: We included 3955 patients who received diagnoses of COPD and
bronchiectasis from 2000 to 2007 from the Taiwan Longitudinal Health Insurance
Database in the BCOS cohort. In the comparison cohort, we included patients with
COPD but without bronchiectasis at a ratio of 4:1, frequency matched by age, sex,
and index year with each patient with BCOS. We followed both cohorts for 5 years
to investigate the incidence and risk of acute respiratory events in the BCOS
cohort relative to the comparison cohort, the incidence rate ratios (IRRs) and
corresponding 95% confidence intervals (CIs) were determined using Poisson
regression models. RESULTS: The BCOS cohort experienced more episodes of acute
respiratory events than did the comparison cohort (16.4 vs 5.52 per 100 person
y). After adjustment for potential covariates, the BCOS cohort had a 2.20-fold
higher risk of pneumonia (adjusted IRR = 2.20, 95% CI = 2.06-2.34), a 3.88-fold
higher risk of acute exacerbation (adjusted IRR = 3.88,95% CI = 3.64-4.13), a
1.74-fold higher risk of acute respiratory failure (adjusted IRR = 1.74,95% CI =
1.47-2.06), and a 1.99-fold higher risk of cardiopulmonary arrest (adjusted IRR =
1.99,95% CI = 1.81-2.20) than did the comparison cohort. CONCLUSION: The patients
with BCOS had a higher risk of acute respiratory events than did COPD patients
without bronchiectasis.
PMID- 29957283
TI - Self-reported task-oriented physical activity: A comparison with objective daily
step count in COPD.
AB - BACKGROUND: Low physical activity (PA) is associated with adverse health outcomes
independent of airflow limitation in COPD. Self-reported assessments are often
limited to global estimates of PA and may not be directly translatable to
patients' goals and motivations. We developed a task-oriented PA checklist and
examined its performance relative to pedometer-assessed daily step count in two
COPD cohorts. METHODS: Task-oriented daily physical activity (DPA) was assessed
in two COPD cohorts using either interviewer-administered recall questionnaire
(DPA-R, Cohort 1, n = 109) or a self-administered diary-format daily checklist
(DPA-C, Cohort 2, n = 175). Daily step count was measured in both cohorts using
the Omron HJ-720 ITC pedometer. Univariate associations between individual DPA
items and [a] cross-sectional and [b] longitudinal change (Cohort 1) in daily
step count were assessed using a Pearson's correlation. Composite scores
comprised of individual DPA items with univariate association p-values <0.1 were
tested for association with daily step count using multivariate models. RESULTS:
Tasks associated with average daily step count in both cohorts included putting
on shoes, showering, washing hair, walking for exercise, the frequency of walks
>10 min, and walking on an incline (Pearson's rho range = 0.14-0.43). A composite
score of these 6 DPA items demonstrated significant associations with baseline
average daily step count in both cohorts (rho = 0.5 & 0.47, Cohorts 1 & 2,
respectively) and longitudinal change in daily step count (rho = 0.46, Cohort 1).
CONCLUSIONS: Self-reported task-oriented assessments complement direct monitoring
and have potential clinical utility in exercise counseling to increase PA among
COPD patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01772082.
PMID- 29957284
TI - Safety of performing transbronchial lung cryobiopsy on hospitalized patients with
interstitial lung disease.
AB - INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) has become a popular option
for tissue diagnosis of interstitial lung disease (ILD), however reports vary
regarding the safety of this procedure. Herein, we evaluate the safety of
transbronchial cryobiopsy in hospitalized patients, comparing adverse events to
outpatient procedures. METHODS AND MEASUREMENTS: This is a single center,
retrospective chart review of all TBLC performed for suspected ILD between
November 2013 and March 2017. Biopsies were performed by a board certified
interventional pulmonologist or interventional pulmonology fellow using a two
scope technique. RESULTS: One hundred fifty-nine cryobiopsies were performed for
the diagnosis of ILD. Rates of adverse events are as follows: pneumothorax 11%,
persistent air leak 1.3%, moderate-severe bleeding 3.8%, ICU transfer within 48 h
3.1%, and all cause 30-day mortality 1.9%. No deaths were attributed to the
procedure. Comparing adverse events between hospitalized patients and
outpatients, rates of pneumothorax were 24% vs 9.9%, persistent air leak 5.9% vs
0.7%, ICU transfer 12% vs 2.1%, and 30-day mortality 5.9% vs 1.4%. However, no
differences were statistically significant. CONCLUSION: Practitioners should
recognize that while cryobiopsies are a high-yield, safe, and cost-effective
alternative to surgical lung biopsy, not all procedures carry the same risk
profiles. Hospitalized patients may have a greater propensity for pneumothorax,
persistent air leak, transfer to the ICU, and 30-day mortality.
PMID- 29957285
TI - Selective upper airway stimulation in older patients.
AB - OBJECTIVE: Selective stimulation of the hypoglossal nerve has proven to be an
effective therapy for patients with obstructive sleep apnea (OSA). The aim of the
study is to investigate the efficacy of selective upper airway stimulation (sUAS)
in older adults. METHODS: All consecutive patients older than 64 years and who
received an implant for sUAS were enrolled. As a control group, an equal number
of patients younger than 65 years with matched apnea hypopnea index (AHI) and
body-mass-index (BMI) were selected. Treatment outcome data were collected
including daytime sleepiness as well as demographics with co-morbidities, BMI,
adverse events and adherence to therapy. RESULTS: 62 patients were included. Both
the control and study group did not differ significantly for AHI, BMI, and
Epworth Sleepiness Scale (ESS) (28.7-28.4/h; 30.1 to 28.4 kg/m2; 14.6 to 12.0
points); but co-morbidities were significantly higher in the study group. Our
data showed no significant difference between the outcomes of study and control
group for AHI, Oxygen desaturation index (ODI) and ESS (6.0-6.0/h; 7.9 to 5.5/h;
5.0 to 7.0 points). Serious adverse events did not occur in both groups and
surgical implantation time did not differ. CONCLUSION: sUAS leads to significant
reductions of AHI, ODI and ESS in older patients. Despite higher age and more co
morbidities, surgical implantation time was not affected. Older patients showed
higher usage of sUAS. Advanced age seems not to be a limiting factor for
treatment outcomes of sUAS, thus indication for this treatment can also be
applied to older people.
PMID- 29957286
TI - Health-related quality of life in Canadians with asthma: A case-control study
using census data.
AB - BACKGROUND: Asthma is a common medical condition that impacts the lives of many
Canadians; yet the health-related quality of life (HRQoL) in persons with asthma
relative to the general population (GP) is poorly studied. In this study, data
from the Canadian Community Health Survey (CCHS) 2013 was used to quantify and
compare the HRQoL of the asthmatic population (AP) and the GP. METHODS: A
representative survey sample of Canadians was taken from the CCHS to compare the
Health Utilities Index Mark 3 (HUI3) scores, a generic HRQoL measure, between the
AP (n = 572) and the GP (n = 6518). The HUI3 multi-attribute utility (MAU) and
the single-attribute utility (SAU) scores between the two sample groups were
studied. The CCHS 2013 dataset was explored as the primary analysis, while the
2012 dataset was used as the confirmatory analysis to verify the consistency of
the results. RESULTS: Clinically important difference was found in the MAU score
between the AP and GP (p < 0.001, Effect size = 0.30). MANOVA on the eight SAU
scores with post-hoc test revealed that the AP had a lower mean score of vision
(p < 0.001, Effect size = 0.36) and pain/disconfort (p < 0.001, Effect size =
0.29). Those findings were consistent with the CCHS 2012 dataset result.
CONCLUSIONS: These results provided evidence that in Canada, having asthma
significantly worsens asthma patients' overall HRQoL and imposes significant
impacts on the patients' vision and pain/discomfort. Therefore, there is room for
improvement in the currently available asthma therapies so patients could achieve
better HRQoL; particular focus should be given to the pain/discomfort and vision
health domains.
PMID- 29957288
TI - Ventilation inhomogeneity and NO and CO diffusing capacity in ex-premature school
children.
AB - AIM: Ex-premature school children show mild-to-moderate airway obstruction and
decreased CO diffusing capacity. Multiple breath nitrogen washout (N2MBW) and NO
diffusing capacity (DLNO) measurements may provide new insight into long-term
pulmonary and vascular impairment in bronchopulmonary dysplasia (BPD). METHODS:
We examined a randomly selected group of 70 ex-premature children (gestational
age <28 weeks or birth weight <1500 g; 42 with and 28 without BPD) and 38 term
born healthy controls of 8-13 years of age. Subjects performed N2MBW (lung
clearance index, LCI; Sacin, and Scond), DLNO (membrane related diffusing
capacity, Dm and pulmonary capillary volume, Vc), Fractional exhaled NO, CO
diffusing capacity, conventional spirometry (FEV1, FVC, FEF25-75) and
plethysmography (RV, TLC). Respiratory symptoms were assessed by questionnaire.
RESULTS: Compared to healthy controls, the BPD group had higher z-scores for lung
clearance index (P = 0.003), Sacin (P = 0.005), lower CO diffusing capacity (P =
0.025), DLNO (P = 0.022), DLNO/VA z-scores (P = 0.025) and a significant larger
proportion had respiratory complaints. Amongst ex-premature children, the BPD
group did not differ from the non-BPD group except for a decreased Dm (P =
0.023). Ex-premature with BPD showed predominantly airway obstruction (FEV1/FVC;
P < 0.0001), signs of hyperinflation (RV/TLC-ratio; P = 0.028), and 25% had a
positive bronchodilator response (>12% in FEV1). CONCLUSION: Ex-premature school
children exhibited relatively mild but significant long-term respiratory symptoms
and pulmonary peripheral impairment judged by N2MBW and DLNO measurements along
with well-known airway obstruction. Larger longitudinal studies are needed to
assess the clinical use of these advanced methods of assessing ventilation
inhomogeneity and DLNO.
PMID- 29957289
TI - Increased poly-beta-hydroxybutyrate production from carbon dioxide in randomly
mutated cells of cyanobacterial strain Synechocystis sp. PCC 6714: Mutant
generation and characterization.
AB - Photosynthetic Poly-beta-hydroxybutyrate (PHB) productivity in cyanobacteria
needs to be increased to make cyanobacterial derived bioplastics economically
feasible and competitive with petroleum-based plastics. In this study, high PHB
yielding mutants of Synechocystis sp. PCC 6714 have been generated by random
mutagenesis, using UV light as a mutagen. The selection of strains was based on
PHB content induced by nitrogen and phosphorus starvation. The fast growing
mutant MT_a24 exhibited more than 2.5-fold higher PHB productivity than that of
the wild-type, attaining values of 37 +/- 4% dry cell weight PHB. The MT_a24 was
characterized for phenotypes, CO2 uptake rate and gene expression levels using
quantitative PCR. Genome sequencing showed that UV mutagenesis treatment resulted
in a point mutation in the ABC-transport complex, phosphate-specific transport
system integral membrane protein A (PstA). The MT_a24 shows potential for
industrial production of PHB and also for carbon capture from the atmosphere or
point sources.
PMID- 29957287
TI - NT-proBNP in stable COPD and future exacerbation risk: Analysis of the SPIROMICS
cohort.
AB - BACKGROUND: High N-terminal pro-brain natriuretic peptide (NT-proBNP) during COPD
exacerbations is associated with worse clinical outcomes. The prognostic value of
NT-proBNP measured during clinical stability has not been well characterized.
METHODS: We studied SPIROMICS participants 40-80 years of age with COPD GOLD
spirometric stages 1-4. The association between baseline NT-proBNP and incident
COPD exacerbations within one year of follow-up was tested using zero-inflated
Poisson regression models adjusted for age, gender, race, body mass index,
current smoking status, smoking history, FEV1 percent predicted, COPD Assessment
Test score, exacerbation history, total lung capacity on chest CT and
cardiovascular disease (any of coronary artery disease, myocardial infarction or
congestive heart failure). RESULTS: Among 1051 participants (mean age 66.1 years,
41.4% women), mean NT-proBNP was 608.9 pg/ml. Subjects in GOLD stage D had the
highest mean NT-proBNP. After one year of follow-up, 268 participants experienced
one or more COPD exacerbations. One standard deviation increase in baseline NT
proBNP was associated with a 13% increase in the risk of incident exacerbations
(incident risk ratio 1.13; 95% CI 1.06-1.19; p < 0.0001). This association was
maintained in participants with and without cardiovascular disease. CONCLUSION:
Baseline NT-proBNP in COPD is an independent predictor of respiratory
exacerbations, even in individuals without overt cardiac disease. The impact of
detection and treatment of early cardiovascular dysfunction on COPD exacerbation
frequency warrants further investigation.
PMID- 29957291
TI - Insights into anaerobic transformation of key dissolved organic matters produced
by thermal hydrolysis sludge pretreatment.
AB - The detailed dissolved organic matters (DOMs) profile by thermal hydrolysis
pretreatment and their transformation during anaerobic digestion (AD) were
investigated. Among the temperature tested, 172 degrees C treatment showed the
best sludge solubilization and the maximum methane production. The study revealed
that high temperature sludge pretreatment mainly improved the release of low
molecular weight (LMW) proteins, LMW neutrals and LMW polysaccharides. Notably,
the effluent from thermal treated sludge digesters contained more DOMs residues.
The predominant residual DOMs were humic substances, LMW proteins and LMW
neutrals. At the molecular level, over 50% of the residual LMW components were
slowly biodegradable or nonbiodegradable steroid-like compounds and aromatics.
Further profiling of the higher MW compounds detected the recalcitrant or
inhibitory compounds, e.g. benzenoids, flavonoids, pyridines and their
derivatives. It is recommended that polishing step should be considered to
further reduce the refractory residues in AD liquor.
PMID- 29957290
TI - The characteristic evolution of soluble microbial product and its effects on
membrane fouling during the development of sponge membrane bioreactor coupled
with fiber bundle anoxic bio-filter for treating saline wastewater.
AB - Membrane fouling mitigation was observed during the development of novel sponge
membrane bioreactor coupled with fiber bundle anoxic bio-filter (AF-MBMBR).
Soluble microbial product (SMP) was found to be positively correlated with
membrane fouling. To further clarify the mechanism of fouling mitigation, the
effects of bio-carriers (sponge and fiber bundles) on characteristics and fouling
potential of SMP were investigated. Characterization of SMP implied that as a
consequence of employing bio-carriers, tyrosine and tryptophan in SMP
significantly decreased, instead relative proportions of humic and fulvic acids
increased. Meanwhile, batch filtration tests demonstrated that fouling potential
of SMP was significantly alleviated, flux decline caused by filtrating SMP
decreased from 84.5% to 60.1%. Further analysis on foulants and filtrate revealed
that proteins performed high adhesion propensity on membrane while humic and
fulvic acids mainly can pass through the membrane; this finding could well
explain the mitigation of SMP fouling potential induced by bio-carriers.
PMID- 29957292
TI - Evaluation of potassium as promoter on anaerobic digestion of saline organic
wastewater.
AB - In this work, the effect of potassium on mesophilic anaerobic digestion (AD) of
saline organic wastewater, which consisted of simulated effluents obtained from
heparin sodium production, was studied. The results showed that the addition of
potassium chloride (KCl) to saline organic wastewater enhanced the AD efficiency.
The optimal dosage was found to be 0.174% when the salt (NaCl) content was 2.0%.
Under this condition, the chemical oxygen demand (COD) removal efficiency,
dehydrogenase activities, and the viability of microorganisms reached 62.7%, 55.7
TF MUL-1, and 78.4%, respectively, which were 115.4%, 77.2%, and 20.3% higher
than those without the addition of potassium chloride. The consumption of
volatile fatty acids (VFAs) was enhanced during the AD process. Moreover, less
humic-like and protein-like residues appeared in the wastewater after AD.
Potassium could maintain the morphology of anaerobic microorganism under high
salinity and showed a long-term effect.
PMID- 29957293
TI - Post-treatment of anaerobic membrane bioreactor (AnMBR) effluent using activated
carbon.
AB - Anaerobic membrane bioreactors (AnMBR) are very effective for wastewater
treatment, however, with the antibiotic ciprofloxacin (CIP) (0-4.7 mg CIP/L) in
the feed their performance decreases, the characteristics of the effluent
changes, and further treatment is needed to recycle or discharge the treated
effluent. Batch experiments using six activated carbons to treat AnMBR effluents
resulting from the treatment of a synthetic wastewater containing ciprofloxacin
were carried out at 35 degrees C. 22-82% COD was removed at a dose of 1 g
activated carbon/L, while size characterization showed the 13.4 kDa and <1 kDa
fractions were the most difficult to adsorb, while CIP was often removed with
high efficiencies of mainly 100%. Significant removal of VFAs also occurred, up
to 100%, and this contributed greatly to COD removal. Nitrogen containing
compounds and phenols showed the highest removal (~100%), whereas other groups
such as esters, alkanes, and alkenes showed lower removal efficiency.
PMID- 29957294
TI - Influence of clay as additive on greenhouse gases emission and maturity
evaluation during chicken manure composting.
AB - To assess the impact of clay as additive on compost maturity and reduction of
greenhouse gases (GHGs) as well as ammonia emission during chicken manure
composting. Six treatments with different dosages of clay (0%, 2%, 4%, 6%, 8% and
10% clay added by dry weight basis of chicken manure and wheat straw) were
designed to conduct an aerobic composting experiment for 50 days. The results
showed that the clay amendment could prolong the thermophilic phase and reduced
the maturity period of composting. In addition, the GHGs (N2O and CH4) and
ammonia emission of clay added treatments were reduced by 25.3-63.4%, 26.01
50.24% and 8.5-70.5%, respectively. But CO2 emission was significantly higher in
10% clay amended treatment. Furthermore, the redundancy analysis showed that C/N
ratio and total organic matter among all physiochemical properties had
significant relationship with GHGs and ammonia emission. Therefore, this study
shown that clay addition can promote maturity, reduced GHGs emission and improve
the quality of product.
PMID- 29957295
TI - Numerical simulation on promoting light/dark cycle frequency to improve
microalgae growth in photobioreactor with serial lantern-shaped draft tube.
AB - Computational fluid dynamics were employed to simulate microalgal cells movement
with enhanced flash-light effects in a gaslift loop-current column
photobioreactor (GLCP) with serial lantern-shaped draft tube (LDT). Clockwise and
anticlockwise vortexes were formed in outer down-flow region of GLCP with LDT.
The radial velocity, axial velocity, and turbulent kinetic energy of microalgal
solution appeared periodical change around the lanterns. The average radial
velocity showed a sixfold improvement from 0.003 m/s to 0.021 m/s, and average
turbulent kinetic energy was enhanced by 18.2% from 22.5 * 10-4 m2/s2 to 26.6 *
10-4 m2/s2, thus increasing light/dark cycle frequency by 54%. The light/dark
cycle frequency increased first and then decreased with an increase of individual
lantern height. The increased lantern number promoted the light/dark cycle
frequency and light time ratio. Microalgal biomass yield in the GLCP with LDT was
improved by 30%, and CO2 fixation peak rate was promoted by 35%.
PMID- 29957296
TI - Up-flow constructed wetland-microbial fuel cell for azo dye, saline, nitrate
remediation and bioelectricity generation: From waste to energy approach.
AB - This study explored the influence of azo dye concentration, salinity (with and
without aeration) and nitrate concentration on bioelectricity generation and
treatment performance in the up-flow constructed wetland-microbial fuel cell
(UFCW-MFC) system. The decolourisation efficiencies were up to 91% for 500 mg/L
of Acid Red 18 (AR18). However, the power density declined with the increment in
azo dye concentration. The results suggest that the combination of salinity and
aeration at an optimum level improved the power performance. The highest power
density achieved was 8.67 mW/m2. The increase of nitrate by 3-fold led to
decrease in decolourisation and power density of the system. The findings
revealed that the electron acceptors (AR18, nitrate and anode) competed at the
anodic region for electrons and the electron transfer pathways would directly
influence the treatment and power performance of UFCW-MFC. The planted UFCW-MFC
significantly outweighed the plant-free control in power performance.
PMID- 29957297
TI - Synaptotagmin-7 controls the size of the reserve and resting pools of synaptic
vesicles in hippocampal neurons.
AB - Continuous neurotransmitter release is subjected to synaptic vesicle
availability, which in turn depends on vesicle recycling and the traffic of
vesicles between pools. We studied the role of Synaptotagmin-7 (Syt-7) in
synaptic vesicle accessibility for release in hippocampal neurons in culture.
Synaptic boutons from Syt-7 knockout (KO) mice displayed normal basal secretion
with no alteration in the RRP size or the probability of release. However,
stronger stimuli revealed an increase in the size of the reserve and resting
vesicle pools in Syt-7 KO boutons compared with WT. These data suggest that Syt-7
plays a significant role in the vesicle pool homeostasis and, consequently, in
the availability of vesicles for synaptic transmission during strong stimulation,
probably, by facilitating advancing synaptic vesicles to the readily releasable
pool.
PMID- 29957298
TI - Finasteride-Nemesis of More Than 1 Urological Cancer?
PMID- 29957299
TI - Depression and survival of glioma patients: A systematic review and meta
analysis.
AB - INTRODUCTION: There is currently a lack of a well-formed consensus regarding the
effects of depression on the survival of glioma patients. A more thorough
understanding of such effects may better highlight the importance of recognizing
depressive symptoms in this patient population and guide treatment plans in the
future. OBJECTIVE: The aim of this meta-analysis was to study the effect of
depression on glioma patients' survival. METHODS: A meta-analysis was conducted
according to the PRISMA guidelines. PubMed, Embase, and Cochrane databases were
searched for studies that reported depression and survival among glioma patients
through 11/06/2016. Both random-effects (RE) and fixed-effect (FE) models were
used to compare survival outcomes in glioma patients with and without depression.
RESULTS: Out of 619 identified articles, six were selected for the meta-analysis.
Using RE model, the various measures for survival outcomes displayed worsened
outcomes for both high and low-grade glioma patients with depression compared to
those without depression. For binary survival outcomes, the overall pooled risk
ratio for survival was 0.70 (95% CI: 0.47, 1.04; 6 studies; I2 = 54.9%, P
heterogeneity = 0.05) for high grade gliomas (HGG) and 0.28 (95% CI: 0.04, 1.78;
I2 = 0%, P-heterogeneity = 1.00; one study) for low grade gliomas (LGG) was. A
sub-group analysis in the HGG group by depression timing (pre- versus post
operative) revealed no differences between depression and survival outcomes (P
interaction = 0.47). For continuous survival outcomes, no statistically
significant difference was found among the high and low-grade glioma groups (P
interaction = 0.31). The standardized mean difference (SMD) in survival outcomes
was -0.56 months (95%CI: -1.13, 0.02; 4 studies, I2 = 89.4%, P-heterogeneity <
0.01) for HGG and -1.69 months (95%CI: -3.26, -0.13; one study; I2 = 0%, P
heterogeneity = 1.00) for LGG. In patients with HGG, the pooled HR of death also
showed a borderline significant increased risk of death among depressive patients
(HR 1.42, 95% CI: 1.00, 2.01). Results using the FE model were not materially
different. CONCLUSIONS: Depression was associated with significantly worsened
survival regardless of time of diagnosis, especially among patients with high
grade glioma.
PMID- 29957300
TI - Naringin protects acrolein-induced pulmonary injuries through modulating
apoptotic signaling and inflammation signaling pathways in mice.
AB - : Acrolein (2-propenal) is ubiquitous in the environment and connections exist
between acrolein exposure and lung cancer risk. Here we investigated the effects
of naringin on acrolein induced-lung injuries in mice. Male C57BL/6 mice were
allocated into four groups: Vehicle group (no acrolein), Naringin only group (80
mg of naringin/kg bw + no acrolein), Acrolein group (ACR group; acrolein), and
Naringin + Acrolein group (NAG+ACR group; 80 mg of naringin/kg bw and acrolein).
The mice were subjected acute acrolein inhalation (10 ppm for 12 h) in an
inhalation chamber and naringin was intraperitoneally administered to the mice
one hour before acrolein exposure. The results demonstrated that, in the NAG+ACR
group, pulmonary injuries (e.g., airspace enlargement, lung inflammation) were
all significantly improved compared to the ACR group. Further, key markers of
MAPK signaling (e.g., p-p38, p-JNK), p53 signaling markers (e.g., p-Chk2, p53),
NF-kappaB signaling axis (e.g., IL-1 beta, TNF-alpha), and oxidative damage
markers (e.g. , GSSG: GSH ratio, oxidative DNA damage) were all effectively
mitigated by the naringin treatment. Naringin provided protection against the
environmental toxicant, acrolein, in mice lung via modulating MAPK, p53, and NF
kappaB signaling pathways and our data may provide significant implications
considering the prevalence of acrolein.
PMID- 29957301
TI - Retraction notice to "Rapamycin induces of protective autophagy in vascular
endothelial cells exposed to oxygen-glucose deprivation" [Brain Res. 1553 (2014)
1-11].
PMID- 29957302
TI - Retraction notice to "Synapse loss regulated by matrix metalloproteinases in
traumatic brain injury is associated with hypoxia-inducible factor-1alpha
expression" [Brain Res. 1268 (2009) 125-134].
PMID- 29957303
TI - Corrigendum to "Minimal detectable change of the Personal and Social Performance
scale in individuals with schizophrenia" [Psychiatry Research 246 (2016) 725
729].
PMID- 29957304
TI - Appearance-related themes in children's animated movies released between 2004 and
2016: A content analysis.
AB - Research suggests that children demonstrate an awareness of cultural messages
regarding appearance; specifically, that thinness is desirable and fatness is
objectionable. In 2004, Herbozo and colleagues published research examining the
content of popular children's movies. This widely cited study has provided the
foundation for various studies examining the impact of media on children. The
purpose of the current study was to extend the findings of Herbozo et al.'s
(2004) research to include more recent movies. Two independent coders viewed the
25 top-grossing U.S. animated feature films since 2004 and indicated the number
of appearance-related themes present in each movie. Movies in the current study
contained significantly more appearance-related themes focused on male
muscularity and the role of personal control related to weight compared to
earlier films. These findings are consistent with cultural trends and demonstrate
the importance of continued examination of children's media influences.
PMID- 29957305
TI - James A. McNamara, Jr.
PMID- 29957306
TI - Authors' response.
PMID- 29957307
TI - Effects of acid etching and calcium chloride immersion on removal torque and bone
cutting ability of orthodontic mini-implants.
AB - INTRODUCTION: The 2-fold purpose of this study was to evaluate the effects of
acid etching and calcium chloride immersion on removal torque and the bone
cutting ability of orthodontic mini-implants (OMIs). METHODS: For the removal
torque part of the study, 3 types of OMIs (titanium alloy) were evaluated in a
rabbit model: OMIs with acid surface etching with and without calcium chloride
immersion (ECG and EG, respectively) and a control group (CG), in which the OMIs
had an untreated, machined surface. We inserted 126 OMIs (42 OMIs per type) into
both tibias of 21 male rabbits (5 months of age) with body weights of 3.0 to 3.5
kg. Removal torque was evaluated after 1, 4, and 7 weeks. To determine the OMIs'
bone-cutting ability, total insertion time to place an OMI 6 mm into artificial
bone was measured (6 OMIs per group). RESULTS: Removal torque values for the EG
(3.97 +/- 0.52 Ncm) and ECG (4.21 +/- 0.44 Ncm) were statistically and
significantly higher than those of the CG (3.02 +/- 0.53 Ncm) 1 week after
implantation (P <0.05). The ECG (6.54 +/- 0.50, 6.61 +/- 0.66 Ncm) showed the
highest removal torque value followed by the EG (5.68 +/- 0.58, 5.89 +/- 0.70
Ncm) and CG (3.43 +/- 0.62, 3.38 +/- 0.54 Ncm) at 4 and 7 weeks after
implantation (P <0.05). Removal torque did not change over time with the CG, but
with the ECG and EG, it was significantly higher in weeks 4 and 7 than in week 1
(P <0.05). Total insertion time was significantly greater for the EG than for the
ECG and CG (P <0.05). CONCLUSIONS: Treating OMIs with a calcium chloride solution
improved the initial bone reaction by preventing contamination of the implant
surface, and increasing the surface roughness of OMIs by acid etching enhanced
their stability without decreasing the bone-cutting ability compared with OMIs
without surface treatment.
PMID- 29957309
TI - Effects of lactoferrin on bone resorption of midpalatal suture during rapid
expansion in rats.
AB - INTRODUCTION: The aim of this study was to investigate the effect of lactoferrin
(LF) on bone resorption of rats' midpalatal sutures during rapid palatal
expansion. METHODS: Sixty male 5-week-old Wistar rats were randomly divided into
3 groups: expansion only (EO), expansion plus LF (E + LF), and sham device
(control). RESULTS: Microcomputed tomography showed that the bone volume/tissue
volume ratio and the relative bone mineral density of the suture bone were
significantly increased in the E + LF group compared with the EO group.
Histochemical staining suggested that the activity of osteoblast-like cells and
the amount of new bone formation were stimulated in the E + LF group whereas the
activity of osteoclasts showed no obvious difference between groups. On the other
hand, the immunohistochemical and the real-time polymerase chain reaction results
showed that the expressions of receptor activator of nuclear factor kappa B
ligand and osteoprotegerin had no significant difference between the EO and E +
LF groups. CONCLUSIONS: These findings demonstrated that LF could stimulate bone
volume and bone density in midpalatal sutures during the suture remodeling
process under tensile force. However, this enhancement effect was not caused by
the reduction of bone resorption.
PMID- 29957311
TI - No prejudices, please.
PMID- 29957310
TI - Conventional surgical-orthodontic approach with double-jaw surgery for a patient
with a skeletal Class III malocclusion: Stability of results 10 years
posttreatment.
AB - This case report presents the treatment of a young man with a skeletal Class III
malocclusion. He was treated with a conventional surgical-orthodontic approach in
which 2 jaw surgeries were performed. The esthetic facial profile, pleasant
smile, appropriate occlusion, and overall good treatment outcome remained stable
10 years after active orthodontic treatment.
PMID- 29957312
TI - Hybrid approach for automatic cephalometric landmark annotation on cone-beam
computed tomography volumes.
AB - INTRODUCTION: Cone-beam computed tomography (CBCT) is commonly used for 3
dimensional (3D) evaluation and treatment planning of patients in orthodontics,
where precision and reproducibility of landmark annotation are required. Manual
landmarking is a time- and effort-consuming task regardless of the practitioner's
experience. We introduce a hybrid algorithm for automatic cephalometric landmark
annotation on CBCT volumes. METHODS: This algorithm is based on a 2-dimensional
holistic search using active shape models in coronal and sagittal related
projections followed by a 3D knowledge-based searching algorithm on subvolumes
for local landmark adjustment. Eighteen landmarks were located on 24 CBCT head
scans from a public dataset. RESULTS: A 2.51-mm mean localization error (SD, 1.60
mm) was achieved when comparing automatic annotations with ground truth.
CONCLUSIONS: The proposed hybrid algorithm shows that a fast initial 2
dimensional landmark search can be useful for a more accurate 3D annotation and
could save computational time compared with a full-volume analysis. Furthermore,
this study shows that full bone structures from CBCT are manageable in a personal
computer for 3D modern cephalometry.
PMID- 29957313
TI - Clinical considerations and potential liability associated with the use of
ionizing radiation in orthodontics.
AB - Ionizing radiation is a known carcinogen. Its damaging effects can be
deterministic or stochastic. Deterministic effects occur only after radiation
exposure thresholds are reached, but stochastic effects are random, and there is
no known threshold below which harmful effects will not occur. Therefore, the use
of ionizing radiation in orthodontic treatment should bring a benefit to the
patient that outweighs the risks. No legally binding statutes, rules, or
regulations provide explicit radiographic prescription protocols for orthodontic
practice. The objective of this article was to discuss guidelines and risk
management strategies for appropriate and defensible use of ionizing radiation in
orthodontics. Guidelines are discussed for radiographic acquisition at different
points along the orthodontic treatment timeline. In addition, risk management
strategies and best practices are presented regarding adequate and defensible
radiographic interpretation. These guidelines are not rigid and do not establish
standards of care; they should be modified as necessary for each patient and each
clinical encounter.
PMID- 29957314
TI - Comparative assessment of treatment efficacy and adverse effects during
nonextraction orthodontic treatment of Class I malocclusion patients with direct
and indirect bonding: A parallel randomized clinical trial.
AB - INTRODUCTION: The objective of this 2-arm parallel trial was to compare the
effects of direct and indirect bonding techniques on the orthodontic treatment
process and outcomes. METHODS: Thirty patients were randomly assigned to undergo
bonding of brackets indirectly (group A, n = 15) or directly (group B, n = 15).
Eligibility criteria included permanent dentition with bilateral Angle Class I
molar and canine relationships, no previous orthodontic treatment, no skeletal
discrepancy, and mild or moderate crowding. The main outcome was the orthodontic
treatment results assessed using the American Board of Orthodontics Objective
Grading System; the secondary outcomes were times taken to perform the laboratory
and clinical steps, total treatment duration, plaque accumulation, formation of
white spot lesions, bond failures, and need for additional archwire bending and
bracket repositioning. The randomization sequence was created using an online
randomization software. The patients were allocated with a 1:1 ratio using a
block size of 4. The sequence generator was contacted by phone for group
assignment after a patient was enrolled for allocation concealment. Blinding was
implemented during the dental cast and radiographic evaluations, data entry, and
data analysis. Patients were evaluated before treatment, and 1, 2, and 6 months
after the start of treatment, and at the end of treatment. RESULTS: All patients
completed the study and were analyzed. There were no dropouts. Marginal ridge
(median difference, -1.000; 95% confidence interval [CI], -2.99 to -0.001; P =
0.03) and total Objective Grading System scores (median difference, -3.999; 95%
CI, -6.000 to -0.005; P = 0.03) were significantly higher in group B than in
group A; other Objective Grading System categories did not differ significantly
between the groups. The clinical time was significantly longer in group B than in
group A (mean difference, -26.51; 95% CI, -29.57 to -23.46; P <0.001), and the
total time was significantly longer in group A than in group B (mean difference,
19.03; 95% CI, 15.32 to 22.74; P <0.001). There were no significant between-group
differences in treatment duration, plaque accumulation, formation of white spot
lesions, bond failure, or need for additional archwire bending or bracket
repositioning. No harms were encountered. CONCLUSIONS: Indirect bonding was
significantly faster than direct bonding in the clinical stage and yielded better
marginal ridge and total scores. Both techniques showed similar rates of plaque
accumulation, formation of white spot lesions, bond failure, and additional
archwire bending and bracket repositioning. REGISTRATION: The trial was not
registered. PROTOCOL: The protocol was not published before trial commencement.
PMID- 29957315
TI - Time for change.
PMID- 29957316
TI - Scoping review of systematic review abstracts about temporomandibular disorders:
Comparison of search years 2004 and 2017.
AB - INTRODUCTION: The purposes of this study were to determine how many systematic
reviews and meta-analyses relating to temporomandibular disorders (TMDs) had been
published as of 2017 compared with those published as of 2004 and then to
summarize the findings, based on an analysis of the abstracts from those studies.
METHODS: A PubMed search was initiated on May 1, 2017. There were 2 separate
searches. The first search was for the topic, "temporomandibular disorders." The
second search was for "temporomandibular disorders and published in the Cochrane
database." The number and the topic category of reviews for 2017 were compared
with those published as of 2004. RESULTS: There were 120 relevant TMD systematic
reviews found in search year 2017: 110 from the PubMed and 10 from the Cochrane
searches. By comparison, there were only 8 TMD systematic reviews published in
2004. The abstracts for all 120 reviews indicated increased roles of genetics and
psychosocial factors in the etiology of TMD. The future of TMD diagnoses appears
to be toward various psychosocial and cellular tests, along with brain
neuroimaging. The reviews on the topic of "treatment" supported conservative,
noninvasive, reversible therapies, with a trend toward more targeted individual
strategies. CONCLUSIONS: There were only 8 TMD systematic reviews published in
2004 compared with 110 in 2017. Overall, the trend has been in the direction of
better diagnostic procedures, more scientific concepts of etiology, and more
conservative treatments for TMD.
PMID- 29957317
TI - Thoughts about "The way it was ...".
PMID- 29957318
TI - Accuracy of clear aligners: A retrospective study of patients who needed
refinement.
AB - INTRODUCTION: The purpose of this study was to determine the accuracy of specific
tooth movements with Invisalign (Align Technology, Santa Clara, Calif). METHODS:
The study sample included 20 Class I adult patients treated with Invisalign; they
completed their first series of aligners and had to have a "refinement" series.
Initial and predicted models were obtained from the initial ClinCheck (Align
Technology). The starting point of the refinement ClinCheck was used to create
the achieved models. Predicted and achieved models were superimposed over the
initial ones on posterior teeth using the 3-dimensional Image Analysis open
source software Slicer CMF. Three hundred ninety-eight teeth were measured for
vertical, horizontal, and rotational movements, and transverse widths were
measured. The amount of predicted tooth movement was compared with the achieved
amount for each movement. RESULTS: Horizontal movements of all incisors seemed to
be accurate, with small (0.20-0.25 mm) or insignificant differences between
predicted and achieved amounts. Vertical movements and particularly intrusions of
maxillary central incisors were found to be less accurate, with a median
difference of 1.5 mm (P <0.001). All achieved rotations were significantly
smaller than those predicted, with the maxillary canines exhibiting the greatest
difference of 3.05 degrees (P <0.001). CONCLUSIONS: The most inaccurate
movements identified in this study were intrusion of the incisors and rotation of
the canines.
PMID- 29957319
TI - The way it really is.
PMID- 29957320
TI - Retrospective evaluation of treatment time and efficiency of a predictable
cantilever system for orthodontic extrusion of impacted maxillary canines.
AB - INTRODUCTION: Orthodontic extrusion of impacted maxillary canines requires
careful biomechanical planning and the use of physiologic force. The aim of this
study was to evaluate the time needed for orthodontic extrusion of impactions of
different severities, using a device that can predictably apply forces under 0.6
N. METHODS: Twenty-two patients who were consecutively treated were selected
retrospectively, and a total of 30 impacted canines were studied. Indexes of
impaction were used to measure severity on pretreatment panoramic radiographs.
Statistical analysis was used to detect interactions between treatment time,
complexity of impaction, age, and sex. RESULTS: Treatment time was highly
dependent on the patient's age; the shortest treatment time was observed in 11-
to 12-year old patients. On the other hand, the severity of impaction had no
effect on treatment time. CONCLUSIONS: Applying physiologic force with the
proposed device resulted in a short treatment time, which depended on the
patient's age more than the impaction complexity. Few complications were
associated with use of this device. Future prospective studies are needed to
replicate these findings and confirm the recommended use of this device.
PMID- 29957321
TI - The sky is not the limit!
PMID- 29957322
TI - Sleep disordered breathing in children seeking orthodontic care.
AB - INTRODUCTION: Our objective was to evaluate the prevalence of high-risk factors
for sleep disordered breathing (SDB) in an orthodontic population of children.
SDB is a spectrum of breathing disorders ranging from primary snoring to
obstructive sleep apnea. METHODS: The sample included 303 healthy children
between the ages of 9 and 17. High risk of SDB was assessed using the Pediatric
Sleep Questionnaire, a validated instrument that consists of 22 questions, and
high risk is defined as positive answers to 33% or more of the questions
answered. Sixteen randomly selected patients repeated the questionnaire 1 month
after the initial survey for reliability. RESULTS: In this sample, high-risk
status on the Pediatric Sleep Questionnaire was not associated with sex, age, or
race. The percentage of patients who were screened as high risk was 7.3% (95%
confidence interval, 4.7%-10.6%). CONCLUSIONS: The results of this study suggest
that approximately 7% of adolescent orthodontic patients may be at a significant
risk for some form of SDB.
PMID- 29957323
TI - Childhood body mass index is associated with early dental development and
eruption in a longitudinal sample from the Iowa Facial Growth Study.
AB - INTRODUCTION: Children with high body mass index (BMI) values have been
demonstrated to have precocious dental development. Research has largely focused
on cross-sectional data sets, leaving an incomplete understanding of the
longitudinal relationship between BMI and dental maturation. METHODS: We used a
pure longitudinal growth series to examine the relationship between dental
development and childhood BMI. Periapical radiographs from 77 children from the
Iowa Growth Study were used to estimate dental development for those with high
BMI values. RESULTS: We confirmed prior studies in finding that children with
higher BMI values were more likely to have advanced dental development for their
ages (P <0.001). BMI at age 4 years was predictive for the timing of dental
development at age 12 (P = 0.052). The precocity of the rate of dental
development accelerated across growth. Overall dental development scores also
correlated with the age of dental eruption for the mandibular canines and first
premolars (P <0.001). CONCLUSIONS: High BMI values at young ages predict advanced
dental development at later times, suggesting a long-term effect of BMI on dental
maturation and implying the need for earlier orthodontic interventions in obese
children. These results corroborate those of previous studies, building further
evidence that relatively early dental eruption is another consequence of
childhood obesity.
PMID- 29957324
TI - What we have to offer.
PMID- 29957325
TI - Impact of altered gingival characteristics on smile esthetics: Laypersons'
perspectives by Q sort methodology.
AB - INTRODUCTION: Smile esthetics includes the white esthetics related to the teeth
and the pink esthetics related to the mucosa. Many surveys have been conducted to
evaluate laypersons' perceptions to altered dental characteristics, but few have
focused on the soft tissue factors. This study was designed to determine the
perceptions of laypeople to variations in soft tissue esthetics during smile.
METHODS: An ideal smile photograph was intentionally altered to produce
variations in gingival inflammation, pigmentation, contour, position of free
gingival margins (with and without recession), zeniths, and interdental papilla.
Sixty-seven images thus produced were rated for attractiveness by 100 laypersons
with the Q sort technique. RESULTS: Variations in interdental papilla (black
triangles) were the most negatively ranked gingival factor by laypersons closely
followed by color changes of the gingiva due to inflammation and pigmentation.
Alteration of gingival contour and gingival zenith had the least impact on smile
esthetics, and changes in the free gingival margin with and without recession
were moderately perceived. Furthermore, laypersons considered unilateral or
asymmetric alterations more unesthetic compared with bilateral or generalized
alterations for factors such as free gingival margin without the recession, and
color changes caused by inflammation and pigmentation. CONCLUSIONS: Laypersons
have considerable negative perception to asymmetric gingival alterations and to
optical color changes caused due to black triangles, inflammation, and
pigmentation of the gingiva. Whereas alteration in gingival contour and zenith
have least impact on smile esthetics.
PMID- 29957326
TI - Lingual mandibular osteonecrosis vs dental impression: A challenging diagnosis.
PMID- 29957327
TI - Three-dimensional evaluation of craniofacial characteristics related to
mandibular asymmetries in skeletal Class I patients.
AB - INTRODUCTION: Our objective was to analyze the characteristics that affect
skeletal Class I adults with mandibular asymmetries using cone-beam computerized
tomography. METHODS: The sample included cone-beam computerized tomography images
of 120 subjects. Asymmetry was determined by the deviation of gnathion from the
midsagittal plane and classified as relative symmetry, moderate asymmetry, or
severe asymmetry. Maxillary and mandibular measurements were made, and the
differences between the contralateral side and the deviated side were evaluated,
as well as the differences between the categories of asymmetry. RESULTS: For
patients with moderate asymmetry, there were significant differences between the
contralateral and deviated sides for some measuments in the transverse and
vertical planes. For those with severe asymmetry, statistically significant
differences were found between the sides for all measurements, except for the
measuments that evaluated the position of the mandibular condyle in the
transverse and sagittal directions. Furthermore, a strong correlation was found
in patients with severe asymmetry, between the deviation of the mandibular dental
midline and the lateral displacement of gnathion. CONCLUSIONS: Patients with
relative symmetry had a bilateral balance, whereas those with moderate and severe
asymmetries showed several skeletal imbalances. A great deviation of the
mandibular dental midline may indicate severe skeletal asymmetry in Class I
adults.
PMID- 29957328
TI - Correlation between midline deviation and condylar position in patients with
Class II malocclusion: A cone-beam computed tomography evaluation.
AB - INTRODUCTION: Midline deviation of the mandible and maxilla can affect
craniofacial growth and occlusion and cause consequences to the temporomandibular
joint. The aim of this study was to evaluate the lateral displacement of the
skeletal and dental midlines in relation to the condyle head position in Class II
patients with cone-beam computed tomography. METHODS: We used 82 cone-beam
computed tomography images. The lateral displacement of the skeletal and dental
midlines considering the 3-dimensional reference plane was analyzed with points
in the maxillary and mandibular central incisors, anterior nasal spine, and
menton. The condyle-fossa relationship, concentric position of the condyles, and
dimensional and positional symmetries between the right and left condyles were
evaluated. RESULTS: There was a statistically significant difference regarding
anterior nasal spine with maxillary central incisor, menton, and mandibular
central incisor points for both sides, and also for maxillary central incisor
menton for the displacement of the left side. We found differences in the
temporomandibular joint for inclination and diameter measurements of the condylar
process. Strong correlations were observed between the maxilla and the condylar
process diameter (right side) and the distance between the geometric centers
(left side), in addition to a strong correlation between the sagittal midline
displacement and the geometric center differences on the right and left sides.
CONCLUSIONS: In patients with Class II malocclusion, lateral displacement of
skeletal and dental midlines in relation to the condyle head position has a
significant correlation with the anteroposterior difference between the geometric
center of the right and left condylar processes.
PMID- 29957329
TI - 3D high resolution imaging for microelectronics: A multi-technique survey on
copper pillars.
AB - In microelectronics, recently developed 3D integration offers the possibility to
stack the dice or wafers vertically instead of putting their different parts next
to one another, in order to save space. As this method becomes of greater
interest, the need for 3D imaging techniques becomes higher. We here report a
study about different 3D characterization techniques applied to copper pillars,
which are used to stack different dice together. Destructive techniques such as
FIB/SEM, FIB/FIB, and PFIB/PFIB slice and view protocols have been assessed, as
well as non-destructive ones, such as laboratory-based and synchrotron-based
computed tomographies. A comparison of those techniques in the specific case of
copper pillars is given, taking into account the constraints linked to the
microelectronics industry, mainly concerning resolution and sample throughput.
Laboratory-based imaging techniques are shown to be relevant in the case of
punctual analyses, while synchrotron based tomographies offer highly resolved
volumes for larger batches of samples.
PMID- 29957330
TI - Multiple strains and polar states in PbZr0.52Ti0.48O3/PbTiO3 superlattices
revealed by aberration-corrected HAADF-STEM imaging.
AB - Tuning multiple strain and polar states of ferroelectrics by using strain
engineering is an essential approach for designing multifunctional electric
devices such as multiple state memories. However, integrating multiple strain
states is still a challenge, and in addition, revealing such strains and the
resultant polar behaviors on the atomic level remains difficult. In this work we
prepare PbZr0.52Ti0.48O3/PbTiO3 (PZT/PTO) superlattices on SrRuO3-buffered
SrTiO3(001) substrates. Aberration-corrected high angle annular dark field
scanning transmission electron microscopy (HAADF-STEM) reveals that the
superlattice is coherent in both c (out-of-plane polar direction) and a (in-plane
polar direction) domains. We find that the strain states of both PZT and PTO in c
and a domains are variant, leading to four special strain states. For example,
the tetragonality for PTO in c and a domains is 1.061 and 1.045, respectively. In
contrast, PZT in c domains displays a tetragonality as giant as 1.107, which
corresponds to 110 uC cm-2 spontaneous polarization, much larger than the bulk
PZT; while PZT in a domains exhibits 1.010 tetragonality with about 70 uC cm-2
polarization. This study reveals a practical way to integrate multiple strain
states and enhanced polarizations in ferroelectric films, which could be used as
multifunctional electric elements.
PMID- 29957331
TI - Interlayer electrical resistivity of rotated graphene layers studied by in-situ
scanning electron microscopy.
AB - Interlayer electrical transport between two-dimensional atomic crystals can be
strongly modulated by the rotational misalignment between them. However, the
experimental study on the interlayer electrical transport between rotated two
dimensional atomic crystals with variable rotation angles is challenging. Here,
an in-situ scanning electron microscopy method is developed to study the
interlayer electrical transport between rotated graphene layers. We employ
nanoprobes installed in a scanning electron microscope to function as both
"fingers" to induce interlayer rotation of a microfabricated metal-graphite-metal
sandwiched island and also electrical probes to measure interlayer electrical
resistivity of the rotated graphene layers. Interlayer electrical resistivity of
the rotated graphene layers is found to increase monotonically by three orders of
magnitude from ~0.1 to ~100 Omega cm when the rotational misalignment angle
increases from 0 degrees to 30 degrees . This phenomenon can be well described
by phonon-mediated electrical transport model. The large-magnitude tunability of
interlayer electrical resistivity by mechanical rotation implies the potential
applications of rotated graphene layers in nanoelectromechanical systems. Our
results also provide a method for studying and tuning interlayer electrical
transport between rotated two-dimensional atomic crystals.
PMID- 29957332
TI - Characterization of Divalent Metal Transporter 1 (DMT1) in Brugia malayi suggests
an intestinal-associated pathway for iron absorption.
AB - Lymphatic filariasis and onchocerciasis are neglected parasitic diseases which
pose a threat to public health in tropical and sub-tropical regions. Strategies
for control and elimination of these diseases by mass drug administration (MDA)
campaigns are designed to reduce symptoms of onchocerciasis and transmission of
both parasites to eventually eliminate the burden on public health. Drugs used
for MDA are predominantly microfilaricidal, and prolonged rounds of treatment are
required for eradication. Understanding parasite biology is crucial to
unravelling the complex processes involved in host-parasite interactions, disease
transmission, parasite immune evasion, and the emergence of drug resistance. In
nematode biology, large gaps still exist in our understanding of iron metabolism,
iron-dependent processes and their regulation. The acquisition of iron from the
host is a crucial determinant of the success of a parasitic infection. Here we
identify a filarial ortholog of Divalent Metal Transporter 1 (DMT1), a member of
a highly conserved family of NRAMP proteins that play an essential role in the
transport of ferrous iron in many species. We cloned and expressed the B. malayi
NRAMP ortholog in the iron-deficient fet3fet4 strain of Saccharomyces cerevisiae,
performed qPCR to estimate stage-specific expression, and localized expression of
this gene by immunohistochemistry. Results from functional iron uptake assays
showed that expression of this gene in the iron transport-deficient yeast strain
significantly rescued growth in low-iron medium. DMT1 was highly expressed in
adult female and male B. malayi and Onchocerca volvulus. Immunolocalization
revealed that DMT1 is expressed in the intestinal brush border, lateral chords,
and reproductive tissues of males and females, areas also inhabited by Wolbachia.
We hypothesize based on our results that DMT1 in B. malayi functions as an iron
transporter. The presence of this transporter in the intestine supports the
hypothesis that iron acquisition by adult females requires oral ingestion and
suggests that the intestine plays a functional role in at least some aspects of
nutrient uptake.
PMID- 29957334
TI - The effects of in utero exposure to the 1918 influenza pandemic on family
formation.
AB - A growing literature ties in utero conditions to life course outcomes, including
education, earnings, and adult health and mortality. A smaller literature has
begun to examine the intergenerational impacts of in utero conditions. A link
between these two literatures-the impacts of in utero conditions on family
formation-has had few examinations but offers a potential set of mechanisms for
the intergenerational reach of early conditions. This paper draws from the 1960
US Decennial Census to examine whether individuals exposed in utero to the
1918/19 influenza pandemic had different family formation patterns than adjacent
unexposed cohorts. The findings suggest small overall effects on marriage rates,
number of children, and several measures of "type" of spouse for men, but
moderate effects for women. For example, women with in utero exposure during
their first trimester marry men with 0.2 fewer years of schooling than those not
exposed. The findings show that exposed individuals have spouses with lower
schooling than unexposed counterparts, this effect is particularly large for
women, and it increases the likelihood of marrying spouses with very low levels
of schooling.
PMID- 29957335
TI - Evolution of quantification methods in oncologic 18F-FDG PET studies.
PMID- 29957333
TI - The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel
from Ixodes scapularis, a tick vector of Lyme disease.
AB - A novel L-glutamate-gated anion channel (IscaGluCl1) has been cloned from the
black-legged tick, Ixodes scapularis, which transmits multiple pathogens
including the agents of Lyme disease and human granulocytic anaplasmosis. When
mRNA encoding IscaGluCl1 was expressed in Xenopus laevis oocytes, we detected
robust 50-400 nA currents in response to 100 MUM L-glutamate. Responses to L
glutamate were concentration-dependent (pEC50 3.64 +/- 0.11). Ibotenate was a
partial agonist on IscaGluCl1. We detected no response to 100 MUM aspartate,
quisqualate, kainate, AMPA or NMDA. Ivermectin at 1 MUM activated IscaGluCl1,
whereas picrotoxinin (pIC50 6.20 +/- 0.04) and the phenylpyrazole fipronil (pIC50
6.90 +/- 0.04) showed concentration-dependent block of the L-glutamate response.
The indole alkaloid okaramine B, isolated from fermentation products of
Penicillium simplicissimum (strain AK40) grown on okara pulp, activated
IscaGluCl1 in a concentration-dependent manner (pEC50 5.43 +/- 0.43) and may
serve as a candidate lead compound for the development of new acaricides.
PMID- 29957336
TI - Analysis of conditions sensitive to primary care in a successful experience of
primary healthcare expansion in Brazil, 1998-2015.
AB - OBJECTIVE: To analyze trends in expansion of coverage of the family health
strategy and hospitalization for conditions sensitive to primary care (CSPC) in a
successful experience of primary healthcare expansion in Brazil. STUDY DESIGN:
Ecological study with data from the Brazilian National Health Information System.
METHODS: CSPC were analyzed between 1998 and 2015 in Rio de Janeiro, Brazil, by
cause groups. Trends, variation, and correlation between indicators in the period
were evaluated. RESULTS: Most of the cause groups showed a reduction in
hospitalization rate, particularly cardiovascular diseases and asthma, but an
increase was seen for obstetric causes. The main causes of hospitalization were
heart failure, cerebrovascular diseases, and bacterial pneumonia. The
contribution of vaccine-preventable diseases, cardiovascular diseases, diabetes,
nutritional deficiencies, and chronic lung diseases to the total number of
hospitalizations was seen to decrease. CONCLUSIONS: Analysis demonstrates that
the family health strategy, as access to the healthcare system, decreases the
majority of CSPC hospitalization rates.
PMID- 29957337
TI - The transmembrane nucleoporin Pom121 ensures efficient HIV-1 pre-integration
complex nuclear import.
AB - HIV-1 hijacks host classical cargo nuclear transportation, or nonclassical
pathways by directly interacting with importin-beta family proteins or
nucleoporins for efficient pre-integration complex (PIC) nuclear import.
Recently, an N-terminal truncated form of nucleoporin Pom121c (601-987 aa) was
reported to inhibit HIV-1 replication. In contrast, we found that HIV-1
replication was significantly decreased in 293T and TZM-b1 cells with siRNA
mediated Pom121 knockdown. Quantitative PCR indicated that viral replication was
impaired at the step of cDNA nuclear import. Furthermore, we found that
karyopherin-beta1 (KPNB1), which belongs to the importin-beta family, interacts
with Pom121 and is involved in Pom121-mediated PIC nuclear import. Rescue
experiment indicated that the FG-repeats and the following alpha-helix in Pom121
are required for its role in HIV-1 PIC nuclear import. Taken together, our
results showed that full-length Pom121 enables efficient PIC nuclear import, and
suggested that this process may rely on KPNB1 dependent classical cargo nuclear
transportation way.
PMID- 29957338
TI - Adventitious viruses persistently infect three commonly used mosquito cell lines.
AB - Mosquito cell lines have been used extensively in research to isolate and
propagate arthropod-borne viruses and understand virus-vector interactions.
Despite their utility as an in vitro tool, these cell lines are poorly defined
and may harbor insect-specific viruses. Accordingly, we screened four commonly
used mosquito cell lines, C6/36 and U4.4 cells from Aedes albopictus, Aag2 cells
from Aedes aegypti, and Hsu cells from Culex quinquefasciatus, for the presence
of adventitious (i.e. exogenous) viruses. All four cell lines stained positive
for double-stranded RNA, indicative of RNA virus replication. We subsequently
identified viruses infecting Aag2, U4.4 and Hsu cell lines using untargeted next
generation sequencing, but not C6/36 cells. PCR confirmation revealed that these
sequences stem from active viral replication and/or integration into the cellular
genome. Our results show that these commonly-used mosquito cell lines are
persistently-infected with several viruses. This finding may be critical to
interpreting data generated in these systems.
PMID- 29957339
TI - Combined and individual strategy of exercise generated preconditioning and low
dose copper nanoparticles serve as superlative approach to ameliorate ISO-induced
myocardial infarction in rats.
AB - BACKGROUND: Myocardial infarction (MI) is a solitary fatal condition with
towering prevalence of mortality worldwide. Our previous study reports that low
dose copper nanoparticles (CuNP) can halt the progression of diabetes-induced
cardiotoxicity as copper has anti-inflammatory, anti-proliferative and anti
oxidant potential. In addition, exercise training has also been considered a
hallmark for cardiac health. METHOD: Cardioprotective potential of CuNP
(1mg/kg/day, po, 4 weeks) and exercise (swimming, 90min, 5days/4 weeks) either
alone or in combination was estimated by measuring the surge in serum
nitrite/nitrate concentration and reduction in creatine kinase MB (CKMB), lactate
dehydrogenase (LDH), cardiac troponin I (cTnI), lipid profile, oxidative stress,
structural abnormalities against isproterenol (ISO)-induced MI. RESULTS: ISO
significantly increased CKMB, LDH, cTnI, lipid alteration, oxidative stress,
structural abnormalities and decrease nitrite/nitrate concentration in serum.
Quantitative estimation of total and phosphorylated Akt(SER-473)/GSK-3b(SER-9)
indicated the significant reduction in pAkt and pGSK-3b in ISO treated animal.
Individual and combined treatment of CuNP and exercise significantly reduce ISO
induced CKMB, cTnI, LDH, and improve nitrite/nitrate concentration and lipid
profile. Attenuation of myocardial oxidative stress and serum TBARS revealed the
associated preconditioning effect of exercise and CuNP against oxidative stress.
Exercise and CuNP also showed the protective potential against structural
abnormalities. However, the cardioprotective effect of individual and combined
strategy of exercise and CuNP was vanished by wortmannin and also avoid the
downregulation of pGSK-3b. CONCLUSION: Low-dose CuNP and exercise training
significantly prevents ISO-induced MI through preconditioning and GSK-3b
inhibition. Ability to upsurge the NO level, lipid profile and reduced oxidative
stress improve the potency of combined strategy.
PMID- 29957340
TI - Cyclophosphamide-modified murine peritoneal macrophages induce CD4+ T
contrasuppressor cells that protect contact sensitivity T effector cells from
suppression.
AB - BACKGROUND: Cyclophosphamide (CY) is one of the most widely used alkylating
agents in the treatment of various cancers and some autoimmune diseases. Numerous
reports suggest that CY exerts immunoregulatory effects. Animal studies have
shown CY affects contact sensitivity (CS) response by depleting CD4+CD25+ T
regulatory cells and CD8+ T suppressor (Ts) cells. In a mouse model of CS, we
previously showed that in vivo treatment with CY shapes the
immunogenic/immunoregulatory balance of peritoneal macrophages. The aim of the
current study is to verify if macrophages (Mf) from CY-treated mice are indeed
able to induce immunoregulatory cells that could protect from suppression.
METHODS: Adoptive cell transfer of CS was used to examine immunomodulating
properties of peritoneal Mf from CY-treated mice. Isolation of peritoneal Mf from
animals that were (Mf-CY) or were not (Mf) treated with CY were cultured to
identify cytokine repertoire. Further, we assessed spleen cell (SPLC) cytokine
production following immunization with trinitrophenyl-conjugated Mf from donors
treated (TNP-Mf-CY) or non-treated (TNP-Mf) with CY. RESULTS: In vitro
experiments identified that Mf-CY produce more IL-6, TNF-alpha and TGF-beta than
naive Mf. Further, immunization with peritoneal TNP-Mf-CY induces CD4+ T
contrasuppressor cells (Tcs) cells that protect CS-effector cells from
suppression. Higher IL-17A secretion was observed from TNP-Mf-CY-treated mouse
SPLC compared to SPLC from TNP-Mf injected mice suggesting that this cytokine
might be important in mediating contrasuppression in this model. CONCLUSIONS: Our
results show that in vivo treatment with CY influences mouse peritoneal Mf to
induce CD4+ Tcs cells that protect CS-effector cells from suppressive signals of
Ts cells.
PMID- 29957341
TI - Anthocyanins and their biosynthetic genes in three novel-colored Rosa rugosa
cultivars and their parents.
AB - The petals of Rosa rugosa are generally pink and purple, never yellow. Although
new varieties of R. rugosa have been bred, no yellow variety has ever been
obtained. Therefore, the use of roses in garden settings has been restricted.
Three R. rugosa hybrid cultivars (R. rugosa 'Miaoyu', 'Rudiepianpian' and
'Jiaomeisanbian') were bred in our laboratory using wild R. rugosa 'Hunchun' as
the female parent and Rosa xanthina as the male parent. The petals of these
cultivars appear yellow, at least in part; thus, these cultivars represent the
first R. rugosa with yellow flowers. To investigate the causes of this yellow
petal color, the petals of these materials were studied at both the physiological
and molecular levels. Anthocyanins are the most important chromogenic substances
in plants. In this study, six types of anthocyanins, cyanidin-3-O-glucoside
(Cy3G), cyanidin-3,5-di-O-glucoside (Cy3G5G), pelargonidin-3-O-glucoside (Pg3G),
pelargonidin-3,5-di-O-glucoside (Pg3G5G), peonidin-3-O-glucoside (Pn3G) and
peonidin-3,5-di-O-glucoside (Pn3G5G), were analyzed in the petals of the new R.
rugosa cultivars and their parents. All of the above anthocyanins were found in
the petals of 'Hunchun', and a small amount of Cy3G5G was present in 'Miaoyu' and
'Jiaomeisanbian', but no anthocyanins were found in R. xanthina or
'Rudiepianpian'. Moreover, the expression levels of seven structural genes
(RrCHS, RrCHI, RrF3H, RrFLS, RrF3'H, RrDFR and RrANS) in the flavonoid
biosynthetic pathway were quantitatively analyzed via qRT-PCR. We concluded that
RrFLS, RrDFR and RrF3'H are the key genes controlling petal color in these
different rose varieties.
PMID- 29957342
TI - 'Concord' grapevine nutritional status and chlorosis rank associated with fungal
and bacterial root zone microbiomes.
AB - Leaf chlorosis in vineyards is associated with reduced crop yields and quality.
While iron (Fe) is understood to play a crucial role in chlorosis, total plant
and soil Fe are not always indicative of chlorosis in grapevines. Physiology of
chlorosis in vineyards has been well-studied, but the soil microbial consequences
of and contributions to chlorosis have received little attention. We used next
generation sequencing (NGS) to examine the bacterial and fungal communities
associated with grapevines demonstrating varying degrees of visual chlorosis
symptoms. Additionally, chemical analyses of soils and grape leaves were used to
explore the influence of plant nutritional status and soil chemistry on microbial
community composition. Finally, factors influencing bacterial community
composition were correlated with predicted bacterial community function. Leaf
tissue magnesium (leaf Mg) concentrations and chlorosis rank were correlated with
bacterial community composition as determined via dbRDA (distance-based
Redundancy Analysis) using Bray-Curtis dissimilarities. Non-metric
multidimensional scaling (NMDS) revealed a significant correlation between fungal
community composition and soil Fe and pH, along with leaf N, Mg, and Ca (mg.kg
1). Chlorosis rank was moderately correlated with KEGG Orthology (KO) terms
associated with nitrogen (N) and carbon (C) metabolism in soils, while leaf Mg
was associated with a spectrum of KO terms including glycosphingolipid
biosynthesis, glycan degradation, transporters, and porphyrin and chlorophyll
metabolism. Additionally, abundance of many bacterial operational taxonomic units
was significantly correlated with leaf Mg, including those from the following
orders: Rhodobacterales, Acidobacteriales, Opitutales, Sphingomonadales,
Burkholderiales, Saprospirales, and Flavobacteriales. Our findings suggest
grapevine chlorosis is interrelated with soil microbial community structure and
function, plant nutrition, and soil chemistry.
PMID- 29957343
TI - Marriage in epilepsy: The impact of the question in knowledge, attitude, and
practice surveys.
AB - BACKGROUND: Knowledge, attitudes, and practice (KAP) questionnaire-based surveys
have captured negative attitudes towards marriage involving people with epilepsy
(PWE). The attitudes may vary according to the nature of the question posed,
whether personal or generic, in addition to many other covariates. METHODS: We
carried out meta-proportion and -regression analyses of epilepsy-related KAP
surveys published between 1970 and 2016 in the medical literature analysis
retrieval system online (MEDLINE) database. RESULTS: The pooled estimate of the
proportion of those responding positively to the marriage question was 0.45 (95%
confidence interval (95%CI): 0.35 to 0.54; I2res = 99.89%). The pooled proportion
of positive responders to a personal question (0.40; 95%CI: 0.35 to 0.46) was
significantly lower than those responding positively to a generic question (0.64;
95%CI: 0.57 to 0.70) (P = 0.001). When modeled individually in regression
analyses, only the continent of origin of the survey (P = 0.001; tau2: 0.06;
I2res: 99.8%; adjusted R2: 11.4%) and subject population type (P = 0.02; tau2:
0.07; I2res: 99.9%; adjusted R2: 4.2%) were associated with the pooled estimate
of positive responders to the question on marriage. CONCLUSIONS: Personal
questions probing the possibility of marriage of self or family members to
someone with epilepsy bring about negative attitudes more often than generic
questions inquiring the marriage-worthiness of PWE.
PMID- 29957344
TI - Foods introduced into Brazil through the border with Argentina and Uruguay:
Pathogen detection and evaluation of hygienic-sanitary quality.
AB - This study aimed to evaluate the presence of pathogens in, and the hygienic
sanitary quality of, commercialized foods of animal origin at the international
border region of Rio Grande do Sul, Brazil. In total, 270 samples of raw and
processed foods of animal origin were collected in Paso de los Libres, Argentina
(n = 65 raw meat, n = 47 dairy products, n = 28 processed meat) and Rivera,
Uruguay (n = 60 raw meat, n = 31 dairy products, n = 29 processed meat), or were
seized by the Brazilian International Agricultural Surveillance System (Brazil
Argentina border) (n = 9 raw meat, n = 1 bush meat). The samples were subjected
to the enumeration of aerobic mesophilic bacteria, enterobacteria, and coagulase
positive staphylococci, and were tested for Salmonella spp., Listeria
monocytogenes, and Escherichia coli O157:H7. The virulence genes for Salmonella
spp. (hilA, invA, spvC, pefA, and sefA), L. monocytogenes (prs, inlA, inlC, and
inlJ) and E. coli O157:H7 (uspA, eae, rfbO157, fliCH7, stx1, stx2, and hlyA) were
investigated using PCR assays. Raw products showed higher counts of aerobic
mesophiles and enterobacteria compared to processed products (P < 0.05). There
were no significant differences in aerobic mesophile or in enterobacterial counts
between identical products according to origin (Argentina vs. Uruguay, P > 0.05).
Escherichia coli O157:H7 was not detected in any of the samples tested.
Salmonella spp. was detected in six (8%) raw products from Argentina. Listeria
monocytogenes was isolated from five (6.66%) raw products originating in
Argentina and 20 (16.66%) raw products from Uruguay. All 52 E. coli isolates
carried the uspA gene, but only one carried the eae gene. The rfbO157, fliCH7,
stx1, stx2, and hlyA genes were not detected. All Salmonella spp. isolates
carried hilA and invA genes, but spvC, pefA, and sefA were not found. All L.
monocytogenes isolates carried the prs gene; however, inlA, inlC, and inlJ genes
were found in 20% of the isolates from Argentina and 95% of those from Uruguay.
To our knowledge, this is the first microbiological study into the hygienic
sanitary quality of animal products in Brazil's land border region. Salmonella
spp. and L. monocytogenes were detected in products of animal origin,
constituting a public health concern and emphasizing the need for an active
surveillance system to reduce the risk of foodborne pathogen introduction into
Brazil.
PMID- 29957345
TI - The effect of the combined use of high pressure treatment and antimicrobial
edible film on the quality of salmon carpaccio.
AB - Fish carpaccio is a ready-to-eat product with a very limited shelf life. In the
present work, the use of high pressure treatment (HP) and/or antimicrobial edible
film was studied in order to improve quality and stability of salmon carpaccio.
In a preliminary part of the work, a film composed of gelatin plus chitosan
incorporating clove essential oil was selected, based on its physicochemical and
antimicrobial properties. Eugenol and beta-caryophyllene, the main volatile
components of the film, migrated to salmon muscle, the release being favored by
HP and storage time. Concurrently, reducing power of the muscle increased,
resulting in prevention of lipid oxidation derived from either HP or refrigerated
storage. HP treatment reduced total microbial counts by 1.5 log cycles from the
onset of storage, whereas the film reduced it by 2 log cycles after 3 days. The
combination of HP and edible film exerted the most intense antimicrobial effect,
total bacterial counts, luminescent bacteria, H2S-producing organisms,
pseudomonads, enterobacteria, and lactic acid bacteria remaining constant or
under detection limit over the whole storage period (11 days). The combined use
of HP treatment and gelatin-chitosan-clove essential oil film is an effective way
of improving quality and stability of salmon carpaccio.
PMID- 29957346
TI - Strategies to enhance fresh produce decontamination using combined treatments of
ultraviolet, washing and disinfectants.
AB - This study investigated the effect of a water-assisted ultraviolet system (WUV;
samples were treated by UV while being immersed in agitated water) on the
inactivation of Salmonella on baby spinach, iceberg lettuce, blueberry, grape
tomato, and baby-cut carrot. The Salmonella inactivation effect of the WUV system
was tested in two scales, and three disinfectants, chlorine, peroxyacetic acid
(PAA) and hydrogen peroxide (H2O2), were tested in combination with the system to
see whether the Salmonella inactivation effect could be enhanced. The fresh
produce samples were dip-inoculated with a Salmonella cocktail to final
concentrations of 4.6-7.6 log CFU/g. To simulate the washing process in the
industry, fresh produce extracts and/or silicon dioxide were added in the wash
water to adjust chemical oxygen demand to ~2000 mg/L and turbidity to >60 NTU. In
general, the decontamination efficacy of WUV treatments followed this order:
Tomato > Carrot > Lettuce ~ Blueberry > Spinach. In the small-scale study, WUV
alone was able to achieve 0.9, 2.6, >3.6, 1.7, and 2.0 log CFU/g reductions of
Salmonella on fresh produce for spinach, lettuce, tomato, blueberry, and carrot,
respectively. For all fresh produce items, WUV combined with PAA could achieve
significantly (P < 0.05) higher Salmonella reduction on fresh produce than
chlorine wash and PAA wash. The WUV treatments combined with chlorine or PAA were
able to keep residual Salmonella in wash water below the detection limit (2
CFU/mL) for almost all the replicates. Similar Salmonella reductions on fresh
produce and in wash water were found in the large-scale study. Considering the
decontamination efficacy on fresh produce, the ability to disinfect the wash
water, and the cost, we recommend chlorine wash for baby spinach, WUV alone for
grape tomato and WUV combined with PAA for iceberg lettuce, blueberry and baby
cut carrot.
PMID- 29957347
TI - DFT investigation on the metabolic mechanisms of theophylline by cytochrome P450
monooxygenase.
AB - Theophylline, one of the most commonly used bronchodilators and respiratory
stimulators for the treatment of acute and chronic asthmatic conditions, can
cause permanent neurological damage through chronic or excessive ingestion. In
this work, DFT calculation was performed to identify the metabolic mechanisms of
theophylline by cytochrome P450 (CYP450) monooxygenase. Two main metabolic
pathways were investigated, namely, N1- (path A) and N3- (path B) demethylations,
which proceeded through N-methyl hydroxylation followed by the decomposition of
the generated carbinolamine species. N-methyl hydroxylation involved a hydrogen
atom transfer (HAT) mechanism, which can be generalized as the N-demethylation
mechanism of xanthine derivatives. The energy gap between the low-spin double
state (LS) and the high-spin quartet state (HS) was low (<1 kcal mol-1),
indicating a two-state reactivity (TSR) mechanism. The generated carbinolamine
species preferred to decompose through the adjacent heteroatom (O6 for path A and
O2 for path B) mediated mechanism. Path B was kinetically more feasible than path
A attributed to its relatively lower activation energy. 1-Methylxanthine
therefore was the energetically favorable metabolite of theophylline. The
observations obtained in the work were in agreement with the experimental
observation, which can offer important implications for further pharmacological
and clinic studies.
PMID- 29957348
TI - The value of clinical and ultrasound features for the diagnosis of infantile
hepatic hemangioma: Comparison with contrast-enhanced CT/MRI.
AB - OBJECTIVES: To investigate the combined use of ultrasound together with clinical
features to differentiate infantile hepatic hemangioma (IHH) from other focal
liver lesions (FLLs) in children and to compare the efficacy of the combined
method to that of CECT/MRI. METHODS: The location, number, size and appearance of
the tumors were evaluated in 45 children with IHH. Another 45 children with FLL
were randomly selected as a control group. Independent factors for predicting IHH
versus FLLs were evaluated. The diagnostic performance of the clinical and
ultrasound features was compared with CECT/MRI. RESULTS: Compared with the
control FLL group, the IHH group had a younger age at diagnosis (P = 0.008),
lower alpha-fetoprotein (AFP) levels (P = 0.000), smaller lesion sizes (P =
0.000), and a higher tumor proportion with a resistance index (RI) of <0.7.
Multiple logistic regression analysis showed that age, size, RI and AFP were
independent factors for predicting IHH. Receiver operating characteristic (ROC)
curve analysis showed that the AUC (area under the curve) of the four combined
independent factors was 0.881 (95% CI: 0.744-0.960), while the AUC for the
CECT/MRI method was 0.905 (95% CI: 0.774-0.973), and the combined AUC for the
independent factors and CECT/MRI was 0.929 (95% CI: 0.805-0.985). There were not
statistically significant among the three AUCs (P > 0.05). CONCLUSIONS: CECT/MRI
was the effective diagnostic indicator for IHH. However, the combined clinical
and ultrasound diagnoses, including age at diagnosis, lesion size, RI and AFP,
can achieve the same effectiveness as CECT/MRI.
PMID- 29957349
TI - Fronto-striatal effective connectivity of working memory in adults with cannabis
use disorder.
AB - Previous working memory (WM) studies found that relative to controls, subjects
with cannabis use disorder (CUD) showed greater brain activation in some regions
(e.g., left [L] and right [R] ventrolateral prefrontal cortex [VLPFC], and L
dorsolateral prefrontal cortex [L-DLPFC]), and lower activation in other regions
(e.g., R-DLPFC). In this study, effective connectivity (EC) analysis was applied
to functional magnetic resonance imaging data acquired from 23 CUD subjects and
23 controls (two groups matched for sociodemographic factors and substance use
history) while performing an n-back WM task with interleaved 2-back and 0-back
periods. A 2-back minus 0-back modulator was defined to measure the modulatory
changes of EC corresponding to the 2-back relative to 0-back conditions. Compared
to the controls, the CUD group showed smaller modulatory change in the R-DLPFC to
L-caudate pathway, and greater modulatory changes in L-DLPFC to L-caudate, R
DLPFC to R-caudate, and R-VLPFC to L-caudate pathways. Based on previous fMRI
studies consistently suggesting that greater brain activations are related to a
compensatory mechanism for cannabis neural effects (less regional brain
activations), the smaller modulatory change in the R-DLPFC to L-caudate EC may be
compensated by the larger modulatory changes in the other prefrontal-striatal ECs
in the CUD individuals.
PMID- 29957350
TI - Heart rate variability analysis in patients with multiple sclerosis.
AB - BACKGROUND: Multiple sclerosis can cause cardiovascular autonomic dysfunction. It
is assumed that is caused by multiple demyelinating plaques localized in the
brain stem and spinal cord. Previous studies have determined this using tilt
table test, heart rate responses to Valsalva maneuver and deep breathing and
heart rate variability analysis with 24 h Holter monitoring. However there is not
a consensus regarding the presence of the relationship between autonomic
dysfunction and severity of multiple sclerosis, type of multiple sclerosis and
expanded disability status scale. The aim of the study is comparison of heart
rate variability between recently diagnosed patients with relapsing-remitting
multiple sclerosis and healthy controls by using 24 h Holter monitoring. Also we
intended to investigate relationship between Expanded Disability Status Scale
score, Multiple Sclerosis Functional Composite scores and cranial and spinal
magnetic resonance imaging findings and hearth rate variability. METHOD: Fifty
one patients with newly diagnosed relapsing-remitting multiple sclerosis and 44
age- and sex-matched healthy controls were compared in this study. Patients with
multiple sclerosis, who were already under immunomodulatory or immunosuppressive
treatment, were excluded from the study. Echocardiography and hearth rate
variability analysis using 24 h period Holter monitoring were performed in all of
the subjects. Echocardiography was used to detect the presence of cardiac
pathology. One multiple sclerosis patient with right ventricular dilatation and
mobile intratrial septum was excluded from the study. All the patients underwent
cranial and cervical spinal magnetic resonance imaging to determine the
relationship between autonomic abnormalities and magnetic resonance imaging.
RESULTS: Our results showed that hearth rate variability values were
significantly lower in patients with multiple sclerosis when compared with
healthy controls: SDNN index (the mean of all the 5 min standard deviations of
normal RR intervals during the 24 h period) (59.80 +/- 17.33 vs. 67.20 +/- 21.28,
p = 0,044), the root-mean-square successive difference (rMSSD) (34.40 +/- 17.50
vs. 38.25 +/- 12.95, p = 0,042), spectral hearth rat variability total power
(3738.84 +/- 2085.51 vs. 4427.44 +/- 1965.71, p = 0,037), spectral hearth rate
variability low frequency (852.03 +/- 450.54 vs. 1011.75 +/- 370.06, p = 0,018).
Ten patients (20%) had brainstem lesion, 25 patients (50%) had cervical lesions
and 10 patients (20%) had thoracic spinal lesions on magnetic resonance imaging.
There was no significant relationship between location of the lesions and heart
rate variability analyses. Also there was no significant relationship between
hearth rate variability values and Expanded Disability Status Scale score,
Multiple Sclerosis Functional Composite scores or number of multiple sclerosis
attack (p > 0,05). CONCLUSION: These findings reveals that our study population
with multiple sclerosis had decreased heart rate variability compared to healthy
controls. This was reflected by dysfunction of both parasympathetic and
sympathetic parameters of hearth rate variability analysis. However, there is no
significant relationship between hearth rate variability analysis and the
findings on cranial, cervical, thoracic spinal magnetic resonance imaging
findings, number of attack, Expanded Disability Status Scale score or Multiple
Sclerosis Functional Composite scores in patients with multiple sclerosis.
PMID- 29957351
TI - Progressive visual function impairment as the predominant symptom of the
transition phase to secondary progressive multiple sclerosis: A case report.
AB - BACKGROUND: No reliable indicators of the transition to the progressive course in
multiple sclerosis (MS) have been identified so far. The main clinical feature of
the progressive phase of MS is usually impairment of walking. Magnetic resonance
imaging and optical coherence tomography have emerged recently as promising tools
to assess increasing neurodegeneration and axonal loss in disease progression in
MS. METHODS: CASE REPORT: RESULTS: We report a case of progressive visual
impairment as the dominant symptom in the transition to secondary progressive MS.
CONCLUSIONS: Impairment of vision, together with walking and cognition, should be
considered to better define the transition from relapsing/remitting to secondary
progressive MS.
PMID- 29957352
TI - Transport mode choice and body mass index: Cross-sectional and longitudinal
evidence from a European-wide study.
AB - BACKGROUND: In the fight against rising overweight and obesity levels, and
unhealthy urban environments, the renaissance of active mobility (cycling and
walking as a transport mode) is encouraging. Transport mode has been shown to be
associated to body mass index (BMI), yet there is limited longitudinal evidence
demonstrating causality. We aimed to associate transport mode and BMI cross
sectionally, but also prospectively in the first ever European-wide longitudinal
study on transport and health. METHODS: Data were from the PASTA project that
recruited adults in seven European cities (Antwerp, Barcelona, London, Oerebro,
Rome, Vienna, Zurich) to complete a series of questionnaires on travel behavior,
physical activity levels, and BMI. To assess the association between transport
mode and BMI as well as change in BMI we performed crude and adjusted linear
mixed-effects modeling for cross-sectional (n = 7380) and longitudinal (n = 2316)
data, respectively. RESULTS: Cross-sectionally, BMI was 0.027 kg/m2 (95%CI 0.015
to 0.040) higher per additional day of car use per month. Inversely, BMI was
0.010 kg/m2 (95%CI -0.020 to -0.0002) lower per additional day of cycling per
month. Changes in BMI were smaller in the longitudinal within-person assessment,
however still statistically significant. BMI decreased in occasional (less than
once per week) and non-cyclists who increased cycling (-0.303 kg/m2, 95%CI -0.530
to -0.077), while frequent (at least once per week) cyclists who stopped cycling
increased their BMI (0.417 kg/m2, 95%CI 0.033 to 0.802). CONCLUSIONS: Our
analyses showed that people lower their BMI when starting or increasing cycling,
demonstrating the health benefits of active mobility.
PMID- 29957353
TI - Estimating household air pollution exposures and health impacts from space
heating in rural China.
AB - Exposure to and the related burden of diseases caused by pollution from solid
fuel cooking, known as household air pollution (HAP), has been incorporated in
the assessment of the Global Burden of Diseases (GBD) project. In contrast, HAP
from space heating using solid fuels, prevalent in countries at middle or high
altitudes, is less studied and missing from the GBD assessment. China is an ideal
example to estimate the bias of exposure and burden of diseases assessment when
space heating is neglected, considering its remarkably changing demands for
heating from the north to the south and a large solid-fuel-dependent rural
population. In this study, based on a meta-analysis of 27 field measurement
studies in rural China, we derive the indoor PM2.5 (fine particulate matter with
an aerodynamic diameter smaller than 2.5 MUm) concentration for both the heating
and non-heating seasons. Combining this dataset with time-activity patterns and
percentage of households using solid fuels, we assess the population-weighted
annual mean exposure to PM2.5 (PWE) and the health impacts associated with HAP in
mainland rural China by county for the year 2010. We find that ignoring heating
impacts leads to an underestimation in PWE estimates by 38 MUg/m3 for the
nationwide rural population (16 to 40 as interquartile range) with substantial
negative bias in northern provinces. Correspondingly, premature deaths and
disability-adjusted life years will be underestimated by approximately 30 * 103
and 60 * 104 in 2010, respectively. Our study poses the need for incorporating
heating effects into HAP risk assessments in China as well as globally.
PMID- 29957354
TI - In vitro assessment of pyrethroid bioaccessibility via particle ingestion.
AB - Due to their intensive use in agricultural and residential pest control, human
exposure to residues of multiple pyrethroids frequently occurs. Pyrethroids have
exceptionally high affinity for solid particles, highlighting the need to
understand human exposure through oral ingestion of contaminated soil or dust
particles. In this study, we used artificial gastrointestinal fluids to measure
the desorption or bioaccessibility of eight current-use pyrethroids in soil and
dust samples. Tenax was further included as a sink in parallel treatments to
simulate the effect of removal due to transfer of pyrethroids to lipid membranes.
The use of 0.4 g of Tenax in 20 mL digestive fluids resulted in rapid and
efficient trapping of pyrethroids, and further, greatly increased
bioaccessibility. In the artificial digestive fluids without Tenax, 6.0-48.0% of
pyrethroids were desorbed over 21 h, and the fractions increased by 1.6-4.1 folds
to 21.5-79.3% with the Tenax sink. Therefore, 6.0-79.3% of soil or dust-borne
pyrethroids may be considered bioavailable upon ingestion. While protein and
sucrose increased the estimated bioaccessibility, co-presence of lipid (vegetable
oil) decreased the bioaccessibility of pyrethroids, likely due to competitive
phase partition. Pyrethroids were also found to be unstable in the artificial
intestinal fluid containing pancreatin, further decreasing the potential
bioaccessibility of pyrethroids on soil or dust particles. The limited
bioaccessibility should be considered to refine the prediction of human exposure
and risk through oral ingestion of pyrethroid residues.
PMID- 29957355
TI - The impact of environmental contamination on the generation of reactive oxygen
and nitrogen species - Consequences for plants and humans.
AB - Environmental contaminants, such as heavy metals, nanomaterials, and pesticides,
induce the formation of reactive oxygen and nitrogen species (RONS). Plants
interact closely with the atmosphere, water, and soil, and consequently RONS
intensely affect their biochemistry. For the past 30 years researchers have
thoroughly examined the role of RONS in plant organisms and oxidative
modifications to cellular components. Hydrogen peroxide, superoxide anion,
nitrogen(II) oxide, and hydroxyl radicals have been found to take part in many
metabolic pathways. In this review the various aspects of the oxidative stress
induced by environmental contamination are described based on an analysis of
literature. The review reinforces the contention that RONS play a dual role, that
is, both a deleterious and a beneficial one, in plants. Environmental
contamination affects human health, also, and so we have additionally described
the impact of RONS on the coupled human - environment system.
PMID- 29957356
TI - Modeling spatial distribution of population for environmental epidemiological
studies: Comparing the exposure estimates using choropleth versus dasymetric
mapping.
AB - Precise population information is critical for identifying more accurate
environmental exposures for air pollution impacts analysis. Basically, there are
two methods for estimating spatial distribution of population, choropleth and
dasymetric mapping. While the choropleth approach accounts for linear
distribution of population over area based on census tract units, the dasymetric
model accounts for a more heterogeneous population density by quantifying the
association between the area-class map data categories and values of the
statistical surface as encoded in the census dataset. Environmental
epidemiological studies have indicated the dasymetric mapping as a more accurate
approach to estimate and characterize population densities in large urban areas.
However, investigations that have attempted to compare the exposure estimates
from choropleth versus dasymetric mapping in environmental health analysis are
still missing. This paper addresses this gap and compares the impact of using
choropleth and dasymetric mapping in different exposure metrics. We compare the
impact of using choropleth and dasymetric mapping in three case studies, defined
here as case study A (relationship between urban structure types and health),
case study B (PM2.5 emissions and human exposure), and case study C (distance
decays of mortality risk related to PM2.5 emitted by traffic along major
highways). These case studies represent previous investigations performed by our
research group where spatial distribution of population was an essential input
for analysis. Our findings indicate that the method used to estimate spatial
distribution of population impacts significantly the exposure estimates. We
observed that the choropleth mapping overestimated exposure for the case study A
and B, while for the case study C the exposure was underestimated by the
choropleth approach. Our findings show that the dasymetric model is a preferred
method for creating spatially-explicit information about population distribution
for health exposure studies. The results presented here can be useful for the
environmental health community to more accurately assess the relationship between
environmental factors and health risks.
PMID- 29957357
TI - Reading strategies of good and poor readers of German with different spelling
abilities.
AB - Reading and spelling abilities are thought to be highly correlated during
development, and orthographic knowledge is assumed to underpin both literacy
skills. Interestingly, recent studies showed that reading and spelling skills can
also dissociate. The current study investigated whether spelling skills
(indicating orthographic knowledge) are associated with the application of
orthographic strategies during reading. We examined eye movements of 137 third-
and fourth-graders who were either good or poor readers with or without a
spelling deficit: 43 children with typical reading and spelling skills, 28 with
isolated spelling deficits, 28 with isolated reading deficits, and 38 with
combined reading and spelling deficits. Although we expected to find reduced
reliance on orthographic reading processes among poor spellers, this was evident
for the group with combined deficits only. Both isolated deficit groups applied
sublexical and lexical processes in a similar amount to typically developing
children. Our findings suggest that reading rests on orthographic strategies even
if lexical representations are poor as indicated by a deficit in spelling skills.
Findings also show that dysfluent reading does not result only from overreliance
on decoding.
PMID- 29957358
TI - Effects of lyotropic anions on thermodynamic stability and dynamics of horse
cytochrome c.
AB - This paper evaluates the effect of various lyotropic anions (chloride, sulfate,
perchlorate, iodide, nitrate, bromide) on the thermodynamic stability and
dynamics of native cytochrome c (Cyt c) at pH 7.0. The results of equilibrium and
kinetic studies revealed that: (i) at low to intermediate concentrations (<= 0.5
M), both chaotropic and kosmotropic anions restrict the dynamics of native
protein, (ii) at relatively higher concentrations (>= 1.0 M), the denaturing
effect of chaotropic anions dominates, which increases the level of structural
fluctuations responsible to unfold the protein according to Hofmeister series
(perchlorate > iodide > nitrate > bromide), and (iii) the lyotropic anions affect
the thermal and global stability of Cyt c according to Hofmeister series. The m
value was determined from DeltaDeltaG vs [Cosolute] plot and was found to be
positive for sulfate and negative for other anions consistent with effect of
lyotopic anions on protein stability according to Hofmeister series.
PMID- 29957359
TI - Bitter melon seed oil increases mitochondrial content in gastrocnemius muscle and
improves running endurance in sedentary C57BL/6J mice.
AB - The alpha-eleostearic acid (alpha-ESA) in bitter melon seed oil (BMSO) is
efficiently converted by the body into rumenic acid. The objective of this study
was to investigate effects of BMSO on skeletal muscle fiber-type switch and
endurance capacity in mice, with or without exercise training. In a 3*2 factorial
design, C57BL/6J mice were fed a 30% high-fat diet composed of soybean oil,
butter or a 1:1 mixture of BMSO and soybean oil, i.e., SB, BT and BM diets,
respectively, and were allocated to be sedentary or undergo exercise (Ex). The Ex
groups received a 15-min training regimen on a motorized treadmill 5 times a
week. After 3-week intervention, endurance capacity was evaluated (total running
time and distance until exhaustion). Mice fed a BM diet had significantly less
body fat, with increased muscle percentage and improved endurance capacity.
Combining sedentary and Ex groups, mice fed a BM diet ran 33% longer and 50%
further than those fed SB, or 25% longer and 36% further than those fed BT
(P<.01). The BM-diet-increased gastrocnemius cytochrome c protein and
mitochondrial DNA content was more prominent in sedentary than in trained mice.
Histochemical staining shows sedentary BM-fed mice had a higher succinate
dehydrogenase activity among groups. Based on a reporter assay, rumenic acid,
rather than alpha-ESA itself, activated PPARdelta ligand binding domain. We
concluded that BMSO improved endurance capacity via stimulation of mitochondrial
biogenesis and function, potentially influencing muscle metabolism and fiber-type
composition in sedentary mice.
PMID- 29957360
TI - Anti-osteoclastic effect of caffeic acid phenethyl ester in murine macrophages
depends upon the suppression of superoxide anion production through the
prevention of an active-Nox1 complex formation.
AB - This study investigated the anti-osteoclastic effect of caffeic acid phenethyl
ester (CAPE) through suppression of Nox1-mediated superoxide anions production.
The multi-nucleated cells were counted and followed by measuring their tartrate
resistant acid phosphatase (TRAP) activity. The superoxide anion production was
determined by using fluorescent probe dihydroethidium (DHE). After one day of
exposure to the receptor activator of nuclear factor-kappaB ligand (RANKL), the
expression of the proteins involved in superoxide anion production was determined
by western blotting. A potent anti-osteoclastic effect of CAPE was observed; the
superoxide anion level reached a maximum value after one day of incubation. CAPE
attenuated the expression of NADPH (nicotinamide adenine dinucleotide phosphate)
oxidase 1 (Nox1) and Rac1, and mitigated the RANKL-induced translocation of
p47phox to the cell membrane. In addition, CAPE suppressed the expression of
nuclear factor-kappa B (NF-kappaB p65), its translocation to the nucleus, and the
activation of NF-kappaB inhibitor (IkappaBalpha) and its kinase (IKKbeta).
Furthermore, CAPE diminished the expression and activation of the c-jun N
terminal kinase (JNK) and the expression of protein-1 activators (AP-1) such as c
Fos and c-Jun. The expression of Nox1 was suppressed by CAPE through the down
regulation of IKKbeta/IkappaBalpha/NF-kappaB and JNK/AP-1 signal pathway. This
study provides evidence that the anti-osteoclastic effect of CAPE depends upon
the attenuated superoxide anion production, which is closely related with
interruption of an active Nox1 complex formation due to the attenuated catalytic
subunit Nox1 expression resulting from suppression of the IKKbeta/IkappaBalpha/NF
kappaB and JNK/AP-1 signaling pathway and the down-regulation of the p47phox
subunit translocation to the cell membrane.
PMID- 29957361
TI - Gamma-tocotrienol attenuates the aberrant lipid mediator production in NLRP3
inflammasome-stimulated macrophages.
AB - The activation of NLRP3 inflammasome in innate immune cells is associated with
enhanced production of pro-inflammatory lipid mediator eicosanoids that play a
crucial role in propagating inflammation. Gamma-tocotrienol (gammaT3) is an
unsaturated vitamin E that has been demonstrated to attenuate NLRP3-inflammasome.
However, the role of gammaT3 in regulating eicosanoid formation is unknown. We
hypothesized that gammaT3 abolishes the eicosanoid production by modulating the
macrophage lipidome. LPS-primed bone marrow-derived macrophages (BMDM) were
stimulated with saturated fatty acids (SFA) along with gammaT3, and the effects
of gammaT3 in modulating macrophage lipidome were quantified by using mass
spectrometry based-shotgun lipidomic approaches. The SFA-mediated inflammasome
activation induced robust changes in lipid species of glycerolipids (GL),
glycerophospholipids (GPL), and sphingolipids in BMDM, which were distinctly
different in the gammaT3-treated BMDM. The gammaT3 treatment caused substantial
decreases of lysophospholipids (LysoPL), diacylglycerol (DAG), and free
arachidonic acid (AA, C20:4), indicating that gammaT3 limits the availability of
AA, the precursor for eicosanoids. This was confirmed by the pulse-chase
experiment using [3H]-AA, and by diminished prostaglandin E2 (PGE2) secretion by
ELISA. Concurrently, gammaT3 inhibited LPS-induced cyclooxygenases 2 (COX2)
induction, further suppressing prostaglandin synthesis. In addition, gammaT3
attenuated ceramide synthesis by transcriptional downregulation of key enzymes
for de novo synthesis. The altered lipid metabolism during inflammation is linked
to reduced ATP production, which was partly rescued by gammaT3. Taken together,
our work revealed that gammaT3 induces distinct modification of the macrophage
lipidome to reduce AA release and corresponding lipid mediator synthesis, leading
to attenuated cellular lipotoxicity.
PMID- 29957362
TI - Effectiveness of cooling therapy (cryotherapy) on leg pain and self-efficacy in
patients with chronic venous disease: A randomized controlled trial.
AB - BACKGROUND: Individuals with chronic venous disease (CVeD) frequently experience
associated leg pain that may influence disease management self-efficacy.
OBJECTIVE: To evaluate the influence of a cooling intervention on leg pain
associated with more severe stages of CVeD and self-efficacy. This was a
secondary aim of the trial. DESIGN: Randomized, blinded, comparator-controlled,
multisite trial. SETTING: Three wound clinics and an academic medical research
center in the United States of America. PARTICIPANTS: 276 participants (54.3%
female, 46.7% male) with stage 4 and 5 CVeD were randomly assigned by computer
generated tables to the cooling intervention group (n = 138) or control group (n
= 138). INTERVENTIONS: Participants received either a cooling (intervention) leg
cuff or placebo cuff (control) to apply topically over the affected skin area.
Both groups performed standard of care including wearing compression wraps and
elevating legs for 30 min during the intervention. Study visits occurred at
baseline, and months 1, 3, 6, and 9. METHODS: Visit measures included: Numeric
Rating Scale (NRS) for short term pain; VEINES-QOL/Sym questionnaire for long
term pain; and, the Self Efficacy for Managing Chronic Disease Scale (SEMCD-6)
for self-efficacy. Data were collected from September 2010 to December 2015 and
analyzed using pooled t-tests, Chi-square tests, and mixed effects models.
Observed 9-month patient retention rates were 94/138 (68.1%) in the intervention
group and 91/138 (65.9%) in the control group. The primary analysis was based on
the intention-to-treat principle. RESULTS: Both the cooling intervention and
control group experienced statistically significant decreases in unadjusted and
adjusted mean NRS pain scores of 1.2 (95% CI: (-1.82, -0.64); p < 0.0001) and 1.8
(95% CI: (-2.31, -1.24); p < 0.0001) respectively from baseline, however, no
statistically significant differences in change scores were observed between
groups. The unadjusted mean VEINES-QOL/Sym pain scores had statistically
significant decreases of 0.9 ((95% CI: (-1.07, -0.62) p < 0.0001 cooling)) and
0.8 (95% CI: (-1.09, -0.55) p < 0.0001 - control) points. When adjusting the
scores for demographic and clinical features, both cooling and control groups
maintained statistically significant decreases (p < 0.001 for both). No
statistically significant differences in change scores were observed between
groups. The unadjusted and adjusted mean self-efficacy scores had no
statistically significant improvements from baseline to month 9 within and
between the cooling and control groups. CONCLUSIONS: Pain was reduced in both
groups while self-efficacy did not change. Findings suggest that strictly
implemented standard of CVeD care in each study group, with or without cooling,
improved pain while there were no effects on self-efficacy.
PMID- 29957363
TI - Tyrosinase inhibition by a rare neolignan: Inhibition kinetics and mechanistic
insights through in vitro and in silico studies.
AB - Neolignans are a large group of polyphenols found in plants and exhibit a wide
range of bioactivities including cytotoxicity, apoptosis inducer, antimalarial
and antifungal effects, acetylcholinesterase, tyrosinase, and alpha-glucosidase
inhibition. In this study we tested acetylcholinesterase (AChE),
butyrylcholinesterase (BuChE), tyrosinase, and alpha-glucosidase inhibitory
effects of a rare neolignan, (-)-4-O-methyldehydrodiconiferyl alcohol 9'-O-beta
glucopyranoside (1) in search for its new pharmaceutical effects. This compound
exhibited good tyrosinase inhibition with an IC50 value of 44.62 +/- 3.99 MUg/mL.
Enzyme kinetics and molecular modelling studies were performed to provide
insights into its tyrosinase inhibition mechanism.
PMID- 29957364
TI - Use of baseline pelvic acceleration during running for classifying response to
muscle strengthening treatment in patellofemoral pain: A preliminary study.
AB - BACKGROUND: Objectively identifying patients at baseline who may not respond well
to a generic muscle strengthening intervention could improve clinical practice by
optimizing treatment strategies. The purpose of this study was to determine
whether pelvic acceleration measures during running, and clinical and demographic
variables could classify patellofemoral pain patients according to their response
to a 6-week hip/core and knee exercise-based rehabilitation protocol. METHODS:
Forty-one individuals with patellofemoral pain participated in a 6-week exercise
intervention program and were sub-grouped into treatment Responders (n = 28) and
Non-responders (n = 13) based on self-reported pain and function measures.
Baseline pelvic acceleration measures were reduced using a principal component
analysis and combined with patient reported outcome measures and demographic
variables in a support vector machine to retrospectively classify patient
treatment response. FINDINGS: The final classification model had 85.4%
classification accuracy, which was significantly better than treatment success
rate, with excellent detection rates for Responders (recall: 96.4%), but 23.1% of
misclassifications among Non-responders (precision: 90.0%). Thus, it resulted in
an F1-score of 0.93 and a Matthews correlation coefficient of 0.69.
INTERPRETATION: Overall, the classifier successfully separated patellofemoral
pain patients into exercise-based treatment Responders and Non-responders based
on a combination of three components of the pelvic accelerations. While this
model requires independent validation, it has the potential for further
development and to be applied in clinical practice and improve treatment
strategies for patellofemoral pain.
PMID- 29957365
TI - It is finally time for adjuvant therapy in melanoma.
AB - Although melanoma is amenable to early detection, there has been no decline in
the mortality rate of this disease and the prognosis of patients with high-risk
primary melanoma or with macroscopic nodal involvement remains poor. The best
option for patients with higher-risk melanoma is to receive effective adjuvant
therapy in order to reduce their chances of recurrence. Multiple systemic
therapeutic agents have been tested as adjuvant therapy for melanoma with durable
benefits seen only with interferon- to date. More recently ipilimumab at the high
dose of 10 mg/kg has shown a significant improvement in terms of Relapse free
survival and Overall survival for stage III melanoma patients but at a
significant cost in terms of immune-related toxicities. More recently, novel
treatment options have emerged. The results from the latest trials with
immunotherapy (PD-1 inhibitors) and molecular targeted therapy (BRAF inhibitor +
MEK inhibitor) have revolutionized the management of adjuvant treatment for
melanoma. As the results from these trials will mature in the next years, a
change in the landscape of adjuvant treatment for melanoma is expected, resulting
in new challenges in treatment decisions such as optimizing patients' selection
through predictive and prognostic biomarkers, and management of treatment related
adverse events, in particular immune related toxicities.
PMID- 29957366
TI - Locally advanced gastro-oesophageal cancer: Recent therapeutic advances and
research directions.
AB - Gastric (GC) and gastro-oesophageal (GOJC) adenocarcinomas are often considered
as a single entity, even though differences exist in epidemiology, clinical
presentation, molecular biology and treatment options. Locally advanced,
resectable disease represents a particularly challenging scenario, as many
critical issues need to be addressed. In both GC and GOJC among Western
countries, systemic chemotherapy demonstrated the greatest benefit when
administered before and after surgery and perioperative chemotherapy has been set
as a standard in this setting. Nonetheless, multiple chemotherapy regimens have
been tested and direct comparisons have been only recently presented. Adjuvant
chemoradiotherapy is an option as well, but several trials have questioned its
role when more effective combination regimens are used. With regards to GOJC,
preoperative chemoradiotherapy is an alternative to perioperative chemotherapy,
as it is associated with higher pathologic responses and a different toxicity
profile: however, a definitive comparison with chemotherapy is ongoing. Herein,
we review the current options for the treatment of resectable GC and GOJC and the
main open questions in the management of these patients, trying to depict an
update of the available algorithms for everyday practice. Moreover, we summarize
the design and preliminary results of the randomized trials in progress that will
hopefully give definitive answers to the most debated issues in the field.
PMID- 29957367
TI - Effect of Diafenthiuron exposure under short and long term experimental
conditions on hematology, serum biochemical profile and elemental composition of
a non-target organism, Labeo rohita.
AB - Diafenthiuron is a thiourea compound that has a novel mode of action as it
inhibits mitochondrial functioning in insect pests. It has been reported in local
newspapers that this pesticide is entering in our fresh water bodies on regular
basis and it is a potential threat for aquatic life. The present study was
designed to determine effect of Diafenthiuron, a commonly used pesticide in
Pakistan, on the hematology, serum biochemical profile and elemental composition
of a non-target organism, Labeo rohita (L. rohita). A sub-lethal dose (0.0075 mg
L-1) of Diafenthiuron was applied under short (2, 4 and 8 days) and long term
(16, 32 and 64 days) experimental conditions. Our results indicated that the
pesticide exposed fish had significantly higher white blood count, lymphocyte,
red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, red cell
distribution width than the control group. However, platelets count, plateletcrit
and platelet distribution width were significantly reduced in Diafenthiuron
treatments than their respective control groups. Concentration of total serum
proteins, albumin, globulin, cholesterol, triglycerides and AST were disturbed in
pesticide exposed treatments compared to control groups. Comparison of elemental
concentrations revealed that calcium, potassium and cadmium concentration varied
significantly when compared between Diafenthiuron treated and untreated L.
rohita. In conclusion, we are reporting that Diafenthiuron can adversely affect
the hematological, serum and elemental concentrations of a non-target organism
like L. rohita and may therefore pose a threat to the food web.
PMID- 29957368
TI - Age of onset and quality of life among males and females with schizophrenia: A
national study.
AB - BACKGROUND: Age of onset is considered central to understanding the course of
schizophrenia, yet little is known regarding its association with quality of life
in general, and specifically among males and females. AIMS: To examine the
association between the age of schizophrenia onset and quality of life, in
general, and among males and females, using data from a national sample and
competing statistical models. METHODS: Participants with a diagnosis of
schizophrenia (N = 1624) completed the Manchester Short Assessment of Quality of
Life (MSA-QoL) and were rated on a parallel measure by their professional
caregivers (N = 578). Multiple regression analysis models were computed for self
appraised quality of life, and mixed models with random intercepts were used for
caregivers. Six competing models were tested for parsimony for each rating
source. Three models without adjustment and three models adjusted for confounding
variables. Sensitivity analyses were conducted for males and females separately.
RESULTS: Age of onset was statistically significantly (P < .05) negatively
associated with self-appraised and caregiver-appraised quality of life on
aggregate and among females. Among males, a significant (P < .01) quadratic
effect of onset age on self-appraised quality of life demonstrated a negative
association up to onset age of 36.67 years, after which the association was
positive. CONCLUSIONS: An earlier age of onset is associated with a better
quality of life in schizophrenia which is tentatively explained by social
decline. Specific trends in psychiatric symptom severity may account for this
association among females while social advantages may account for the particular
results found among males.
PMID- 29957369
TI - Changes in attitude towards LAI antipsychotic maintenance treatment: A two-year
follow-up study.
AB - BACKGROUND: To present real-world evidence on the effects of switching from oral
to long-acting injectable (LAI) antipsychotic maintenance treatment (AMT) in a
sample of clinically stable patients with schizophrenia, with regard to
subjective experience of treatment, attitude towards drug and quality of life.
METHODS: 50 clinically stable adult schizophrenic outpatients were recruited. At
the time of enrolment (T0), all patients were under a stabilized therapy with a
single oral second-generation antipsychotic (SGA) and were switched to the
equivalent maintenance regimen with the long-acting formulation of the same
antipsychotic. 43 patients completed the 24-month prospective, longitudinal, open
label, observational study. Participants were assessed at baseline (T0), after 12
(T1) and 24 months (T2), using psychometric scales (PANSS, YMRS and MDRS) and
patient-reported outcome measures (SWN-K, DAI-10 and SF-36). RESULTS: The switch
to LAI-AMT was associated with a significant clinical improvement at T1 and T2
compared to baseline (T0). All of the psychometric indexes, as well as patients'
subjective experience of treatment (SWN-K), and quality of life (SF-36) showed a
significant improvement after one year of LAI-AMT, with stable results after two
years. Patients' attitude towards drug (DAI-10) increased throughout the follow
up period, with a further improvement during the second year. CONCLUSIONS: The
switch to LAI-AMT may help to address the subjective core of an optimal recovery
in stabilized schizophrenic patients. A sustained improvement in patients'
attitude towards drug may help to achieve patient's compliance. The size of this
study needs to be expanded to produce more solid and generalizable results.
PMID- 29957370
TI - Effectiveness of watchful waiting versus antidepressants for patients diagnosed
of mild to moderate depression in primary care: A 12-month pragmatic clinical
trial (INFAP study).
AB - BACKGROUND: Although mild to moderate major depressive disorder (MDD) is one of
the main reasons for consulting a general practitioner (GP), there is still no
international consensus on the most appropriate therapeutic approach. METHODS:
The aim of this study is to evaluate the clinical effectiveness of watchful
waiting (WW) compared with the use of antidepressants (ADs) for the treatment of
mild to moderate depressive symptoms in 263 primary care (PC) usual-practice
patients in a 12-month pragmatic non-randomised controlled trial. Both
longitudinal and per-protocol analyses were performed, through a multilevel
longitudinal analysis and a sensitivity analysis. RESULTS: We observed a
statistically significant time x treatment interaction in the severity of
depression (Patient Health Questionnaire, PHQ-9) and disability (World Health
Organization Disability Assessment Schedule, WHODAS) in favour of the AD group at
6 months but not at 12 months. The effect size of this difference was small. No
statistically significant differences were observed between groups in severity of
anxiety (Beck Anxiety Inventory, BAI) or health-related quality-of-life (EuroQol
5D, EQ-5D). Sensitivity analysis and per-protocol analysis showed no differences
between the two groups in any of the evaluated scales. CONCLUSIONS: Superiority
of either treatment (WW and AD) was not demonstrated in patients treated for
depression in PC after one year of follow-up.
PMID- 29957371
TI - Burnout in mental health professionals: A systematic review and meta-analysis of
prevalence and determinants.
AB - This study aimed to estimate the level of burnout in mental health professionals
and to identify specific determinants of burnout in this population. A systematic
search of MEDLINE/PubMed, PsychINFO/Ovid, Embase, CINAHL/EBSCO and Web of Science
was conducted for original research published between 1997 and 2017. Sixty-two
studies were identified as meeting the study criteria for the systematic review.
Data on the means, standard deviations, and prevalence of the dimensions of
burnout were extracted from 33 studies and included in the meta-analysis (n =
9409). The overall estimated pooled prevalence for emotional exhaustion was 40%
(CI 31%-48%) for depersonalisation was 22% (CI 15%-29%) and for low levels of
personal accomplishment was 19% (CI 13%-25%). The random effects estimate of the
mean scores on the Maslach Burnout Inventory indicate that the average mental
health professional has high levels of emotional exhaustion [mean 21.11 (95% CI
19.98, 22.24)], moderate levels of depersonalisation [mean 6.76 (95% CI 6.11,
7.42)] but retains reasonable levels of personal accomplishment [mean 34.60 (95%
CI 32.99, 36.21)]. Increasing age was found to be associated with an increased
risk of depersonalisation but also a heightened sense of personal accomplishment.
Work-related factors such as workload and relationships at work, are key
determinants for burnout, while role clarity, a sense of professional autonomy, a
sense of being fairly treated, and access to regular clinical supervision appear
to be protective. Staff working in community mental health teams may be more
vulnerable to burnout than those working in some specialist community teams,
e.g., assertive outreach, crisis teams.
PMID- 29957372
TI - Borderline resectable pancreatic cancer. Challenges and controversies.
AB - Pancreatic cancer is a dismal disease with an increasing incidence. Despite the
majority of patients are not candidates for curative surgery, a subgroup of
patients classified as borderline resectable pancreatic cancer can be selected in
whom a sequential strategy of neoadjuvant therapy followed by surgery can provide
better outcomes. Multidisciplinary approach and surgical pancreatic expertise are
essential for successfully treating these patients. However, the lack of
consensual definitions and therapies make the results of studies very difficult
to interpret and hard to be implemented in some settings. In this article, we
review the challenges of borderline resectable pancreatic cancer, the complexity
of its management and controversies and point out where further research and
international cooperation for a consensus strategy is urgently needed.
PMID- 29957373
TI - Does pelvic radiation increase rectal cancer incidence? - A systematic review and
meta-analysis.
AB - BACKGROUND: One of the late complications associated with radiation therapy (RT)
is a possible increased risk of second cancer. In this systematic review, we
analysed the incidence of rectal cancer following primary pelvic cancer
irradiation. METHODS: A literature search was conducted using the PubMed and
EMBASE libraries. Original articles that reported on secondary rectal cancer
after previous RT for a primary pelvic cancer were included. Sensitivity analyses
were performed by correcting for low number of events, high risk of bias, and
outlying results. RESULTS: A total of 5171 citations were identified during the
literature search, 23 studies were included in the meta-analyses after screening.
A pooled analysis, irrespective of primary tumour location, showed an increased
risk for rectal cancer following RT (N = 403.243) compared with non-irradiated
patients (N = 615.530) with a relative risk (RR) of 1.43 (95% confidence interval
[CI] 1.18-1.72). Organ specific meta-analysis showed an increased risk for rectal
cancer after RT for prostate (RR 1.36, 95%CI 1.10-1.67) and cervical cancer (RR
1.61, 95% CI 1.10-2.35). No relation was seen in ovarian cancer patients. The
modality of RT did not influence the incidence of rectal cancer. CONCLUSIONS:
This review demonstrates an increased risk for second primary rectal cancer in
patients who received RT to the pelvic region. This increased risk was modest and
could not be confirmed for all primary pelvic cancer sites. The present study
does not provide data to change guidelines for surveillance for rectal cancer in
previously irradiated patients.
PMID- 29957374
TI - Suicidal ideation in adult ADHD: Gender difference with a specific
psychopathological profile.
AB - OBJECTIVE: To investigate suicidal ideation (SI) in patients with adult ADHD
(aADHD), and its association with gender and psychopathology. METHODS: Case
control study with 206 participants (patients = 103/healthy controls = 103;
matched on gender, age, and education). SI was assessed by the Beck-I Depression
Inventory. The Conners' Adult ADHD Rating Scale (CAARS) was used to characterize
the ADHD symptom-domains. RESULTS: Compared to controls, the likelihood of SI was
significantly higher in females with ADHD (odds ratio[OR] = 25.0 (95%CI:2.98
200.0); the difference was not significant in males (OR = 2.09 (95%CI:0.75-5.81).
In females, "Problems with Self-Concept" scores on the CAARS showed the closest
association with SI (OR = 5.60,95%CI:2.34-13.41]), while in males it was
"Impulsivity" scores (OR = 3.01,95%CI:1.50-6.06). CONCLUSION: Our findings extend
previously described transdiagnostic associations of specific psychopathological
risk factors to aADHD, including problems with self-concept and impulsivity,
which are robustly associated with suicidality across diagnostic boundaries. In
addition, they indicate that these associations exhibit pronounced gender
specificity in aADHD.
PMID- 29957375
TI - Body trust as a moderator of the association between exercise dependence and
suicidality.
AB - OBJECTIVES: Exercise dependence and interoceptive deficits, particularly low body
trust, have been associated with suicidality. This study tested whether low body
trust predicted current suicidal ideation and past suicide attempts in
individuals exhibiting symptoms of exercise dependence. METHODS: 540 individuals
(55.6% female, mean age 36) recruited via MTurk completed online measures of
exercise dependence, interoception, and history of suicidal ideation and
attempts. RESULTS: Exercise dependence symptoms and low body trust were
associated with suicidal ideation. Body trust moderated the relationship between
exercise dependence symptoms and suicidal ideation. Continuance in exercise
despite adverse consequences and low body trust were associated with past suicide
attempts. CONCLUSIONS: Body trust was associated with suicidal ideation and
suicide attempts in individuals with exercise dependence symptoms, and the
associations strengthened as body trust decreased. The experience of not trusting
one's own body may exacerbate suicide risk in at-risk individuals.
PMID- 29957376
TI - Imaging and spatially resolved quantification of drug distribution in tissues by
mass spectrometry.
AB - Mass spectrometry imaging (MSI) is a powerful label-free technique for
visualizing drug and metabolite distributions in biological tissues. In this
review, we discuss recent developments in MSI and spatial profiling technologies
to visualize and quantify drug distributions in tissues. We also present recent
examples of applications of these technologies for assessing drug distribution
within tissues and individual cells. Finally, we focus on an emerging technique
coupling laser capture microdissection (LCM) to quantitative mass spectrometry,
which combines the respective advantages of imaging and conventional liquid
chromatography mass spectrometry, and thus enables spatially resolved drug
quantification.
PMID- 29957377
TI - Permeability and fluid flow-induced wall shear stress of bone tissue scaffolds:
Computational fluid dynamic analysis using Newtonian and non-Newtonian blood flow
models.
AB - Among the factors that are important in successful bone tissue regeneration
through scaffolds are permeability and fluid flow-induced wall shear stress (WSS)
because of the direct contribution of these factors to cell bioactivities. The
permeability of scaffolds is usually measured using fluids such as water, which
are characterized as Newtonian materials with constant viscosity. However, using
the fluid properties of blood as bases in measuring permeability can lead to more
realistic results given that scaffolds are implanted in the body, where the only
flowing fluid (i.e., blood) is a non-Newtonian fluid. Moreover, the linear
relationship of WSS with fluid viscosity challenges the use of Newtonian fluids
in determining WSS magnitude. With consideration for these issues, we
investigated permeability and WSS through computational fluid dynamics (CFD)
analyses of lattice-based and gyroid scaffold architectures with Newtonian and
non-Newtonian blood flow properties. With reference to geometrical parameters and
the pressure drops derived from the CFD analyses, the permeability levels of the
Newtonian and non-Newtonian models were calculated by exploiting the classic and
modified Darcy's equations, respectively. Results showed that both scaffold
architectures were several times more permeable in the Newtonian blood flow
models than in their non-Newtonian counterparts. Within the scaffolds, the non
Newtonian flow of blood caused almost twice the magnitude of WSS originating from
Newtonian blood flow. These striking discrepancies in permeability and WSS
between the two blood models were due to differences in their viscosity
behaviors.
PMID- 29957378
TI - Projective geometric model for automatic determination of X-ray-emitting source
of a standard radiographic system.
AB - BACKGROUND AND OBJECTIVE: Currently, many orthopedic operations are planned by
analyzing X-rays. The exact position of the focus is needed to calculate the real
size of an object that is represented in conical projection, although in
practice, this position is difficult to determine using current X-ray commercial
systems. In this paper, a new geometric model is proposed in order to determine
accurately, practically, and economically the location of the emitting source of
commercial imaging systems using a single standard X-ray image. METHOD: The
method requires a specific reference locator object to be positioned in the
visual field of radiographic image. Because this object cannot implement ideal
geometric points, but instead works with small spheres, it was necessary to
experimentally validate the proposed methodology. The implemented software that
was developed to validate the model was used in four series of tests. In these
tests, we studied the influence on the final result of: 1. the selection of a
specific set of markers in radiography, 2. the focus position variation in
relation to radiograph and 3. the possible rotated angle of locator object about
Z axis. RESULTS: The results for 164 tests that were performed with this software
showed that the expected error for 99.5% of values ranges with maximum error of [
0.35%, +0.39%], which shows that the model is independent of the design of
locator object and its position and orientation in the radiographic field. The
software used to validate the proposed model has been found useful to verify its
reliability, effectiveness, ease of implementation, and accuracy. CONCLUSIONS:
This model is effective to calculate the precise position of the X-ray focus of
any standard radiographic system accurately.
PMID- 29957379
TI - The spleen as a neuroimmune interface after spinal cord injury.
AB - Traumatic spinal cord injury (SCI) causes widespread damage to neurons, glia and
endothelia located throughout the spinal parenchyma. In response to the injury,
resident and blood-derived leukocytes orchestrate an intraspinal inflammatory
response that propagates secondary neuropathology and also promotes tissue
repair. SCI also negatively affects autonomic control over peripheral immune
organs, notably the spleen. The spleen is the largest secondary lymphoid organ in
mammals, with major roles in blood filtration and host defense. Splenic function
is carefully regulated by neuroendocrine mechanisms that ensure that the immune
responses to infection or injury are proportionate to the initiating stimulus,
and can be terminated when the stimulus is cleared. After SCI, control over the
viscera, including endocrine and lymphoid tissues is lost due to damage to spinal
autonomic (sympathetic) circuitry. This review begins by examining the normal
structure and function of the spleen including patterns of innervation and the
role played by the nervous system in regulating spleen function. We then describe
how after SCI, loss of proper neural control over splenic function leads to
systems-wide neuropathology, immune suppression and autoimmunity. We conclude by
discussing opportunities for targeting the spleen to restore immune homeostasis,
reduce morbidity and mortality, and improve functional recovery after SCI.
PMID- 29957380
TI - Immune cell profiling in the cerebrospinal fluid of patients with primary
angiitis of the central nervous system reflects the heterogeneity of the disease.
AB - Primary angiitis of the central nervous system (PACNS) is a rare and
heterogeneous inflammatory disease of the CNS vasculature with poorly understood
pathophysiology. Comprehensive immune-cell phenotyping revealed increased
frequencies of leukocytes in the cerebrospinal fluid (CSF) of PACNS patients
compared to patients with multiple sclerosis, ischemic stroke, and somatoform
disorders (n = 18 per group). Changes in the intrathecal immune-cell profile were
heterogeneous in PACNS. While proportions of T-cell subsets remained unaltered,
some PACNS patients showed a shift toward NK- or B cells. Intrathecal
immunoglobulin synthesis was observed in a subgroup of PACNS patients with an
increased frequency of antibody producing plasma cells.
PMID- 29957381
TI - HLA-DRB1 polymorphism and susceptibility to multiple sclerosis in the Middle East
North Africa region: A systematic review and meta-analysis.
AB - This meta-analysis explores association of HLA-DRB1 alleles with MS risk in the
Middle-east North Africa (MENA) countries. Divided into two groups of alleles (10
studies, 899 cases/1457 controls) and phenotypes (8 studies, 1,040 cases/1,256
controls), Odds ratios (ORs) of DRB1 distribution in MS subjects were assessed
using Cochrane RevMan software. DRB1*15 demonstrated significant association with
MS in both groups (OR=1.6 and OR=2.51, respectively). In phenotypes, DRB1*03 and
DRB1*04 had predisposing role (OR=1.8 and OR=1.9), while DRB1*07 and DRB1*11 were
protective (OR=0.56 and OR=0.67). Similar but non-significant trends were seen
among alleles, which in sum coincides with a Caucasian-like pattern.
PMID- 29957382
TI - Up-regulation of MU-, delta- and kappa-opioid receptors in concanavalin A
stimulated rat spleen lymphocytes.
AB - Regulation of MU-, delta- and kappa-opioid receptor protein level in spleen
lymphocytes when stimulated by mitogen is not known. To answer the question
whether these cells do express opioid receptor (OR) proteins, primary, fresh rat
spleen lymphocytes were prepared and stimulated for 48 h with mitogenic dose of
Con A. The unstimulated lymphocytes did not express MU- and delta-OR proteins in
detectable amounts, however, stimulation with Con A resulted in appearance of
clearly detectable immunoblot signals of both MU-OR and delta-OR. kappa-OR were
detected already in primary cells and increased 2.4-fold in Con A-stimulated
cells. These results were supported by data obtained by flow cytometry analysis
indicating a dramatic increase in number of MU-, delta- and kappa-OR expressing
cells after mitogen stimulation. The newly synthesized MU-, delta- and kappa-OR
in Con A-stimulated spleen lymphocytes were present in the cells interior and not
functionally mature, at least in terms of their ability to enhance activity of
trimeric G proteins determined by three different protocols of agonist
stimulated, high-affinity [35S]GTPgammaS binding assay. The up-regulation of MU-,
delta- and kappa-OR was associated with specific decrease of their cognate
trimeric G proteins, Gi1alpha/Gi2alpha; the other Galpha and Gbeta subunits were
unchanged. The level of beta-arrestin-1/2 was also decreased in Con A-stimulated
splenocytes. We conclude that up-regulation of OR expression level in spleen
lymphocytes by Con A proceeds in conjunction with down-regulation of their
intracellular signaling partners, Gi1alpha/Gi2alpha proteins and beta-arrestin
1/2. These regulatory proteins are expressed in high amounts already in
unstimulated cells and decreased by mitogen stimulation.
PMID- 29957383
TI - Sildenafil ameliorates EAE by decreasing apoptosis in the spinal cord of C57BL/6
mice.
AB - Apoptosis is one form of cell death that is intimately related to health and
pathological conditions. In most neuroinflammatory and/or neurodegenerative
diseases, apoptosis is associated with disease development and pathology and
inhibition of this process leads to considerable amelioration. It is becoming
evident that apoptosis also participates in the pathogenesis of Multiple
Sclerosis (MS) and its animal model, Experimental Autoimmune Encephalomyelitis
(EAE). Drugs such as Sildenafil, a Phosphodiesterase type 5 Inhibitor (PDE5I),
have proven to be neuroprotective in MS models. However, it is not known whether
Sildenafil is able to modulate cell death, specifically apoptosis, in EAE mice.
Therefore, the aim of this study was to determine the effects of Sildenafil on
extrinsic and intrinsic apoptosis pathways in the spinal cord of C57BL/6 mice
with EAE. TUNEL analysis showed that EAE mice had elevated number of TUNEL+ cells
and that treatment with Sildenafil led to reduced number of dying cells,
indicating that Sildenafil was able to inhibit cell death. We observed that both
extrinsic and intrinsic pathways of apoptosis were governing the dynamics of EAE
progression. We showed that in EAE mice there were increased levels of extrinsic
(Caspase-8, -3, TNF-alpha, FADD) and intrinsic (Caspase-9, Bax and Cytochrome C)
apoptosis markers. Bcl-2, an anti-apoptotic protein, was downregulated in EAE
mice. We also demonstrated that EAE mice had increased levels of non-caspase
mediators of cell survival/cell death (p-IkappaBalpha and p-MAPK-p38). Besides,
EAE mice presented augmented demyelination. Nevertheless, this is the first
research to demonstrate that Sildenafil, when administered concomitant to disease
induction, modulated the expression of pro- and anti-apoptotic proteins of the
extrinsic and intrinsic pathways, as well as diminished the expression of non
caspase mediators and promoted remyelination in the spinal cord, indicating
neuroprotective effects. Thus, the present study demonstrated that Sildenafil
inhibits apoptosis by two distinct, although interconnected, mechanisms: directly
by modulating caspase expression (through extrinsic and intrinsic pathways) and
indirectly by modulating the expression of molecules involved in cell death
and/or cell survival.
PMID- 29957384
TI - Does pregnancy affect women with multiple sclerosis? A prospective study in
Western China.
AB - OBJECTIVES: Pregnancy is considered to be protective for multiple sclerosis (MS)
but little is known about Asian MS women. Our study aimed to investigate whether
pregnancy affects the course of MS and whether MS affects pregnancy in a Chinese
cohort. METHODS: We established a database (2009-2016) of 94 females with MS in
the Department of Neurology at West China Hospital. From this database, we
enrolled females who had been pregnant before or after the clinical onset of MS
and consecutively followed up the patients and their offspring for at least one
year after delivery. We registered their demographic, clinical and pregnancy
related information, as well as the annualized relapse rate (ARR) and Expanded
Disability Status Scale (EDSS) score. RESULTS: We enrolled 55 females with MS and
126 pregnancies. Among them, 14 females had 15 deliveries after MS onset. In
these 15 full-term pregnancies after MS onset, the average ARR decreased from
0.46 +/- 0.52 in the year before pregnancy to 0.07 +/- 0.26 (P = .034) during
pregnancy and no drug exposure were observed during pregnancy. The average EDSS
score at one year after delivery (1.50 +/- 1.72) was higher than that at
conception (0.77 +/- 1.35; P = .045). CONCLUSIONS: The natural history of MS
during pregnancy suggests that full-term pregnancy protects MS females from
relapse. However, the disability of MS females may develop after delivery.
PMID- 29957385
TI - Prevalence of immunological diseases in a Finnish frontotemporal lobar
degeneration cohort with the C9orf72 repeat expansion carriers and non-carriers.
AB - Recent studies have suggested a role for immune dysregulation behind the etiology
of frontotemporal lobar degeneration (FTLD). Here, we have investigated the
prevalence of immunological diseases in FTLD (N = 196) with and without the
C9orf72 repeat expansion, Alzheimer's disease (AD) (N = 193) and not cognitively
impaired (NCI) subjects (N = 92). The prevalence was 16.3% in FTLD, 13.5% in AD
and 15.2% in NCI. Although differences between the groups did not reach
statistical significance, the frequency of immunological diseases was the highest
in FTLD without the C9orf72 expansion (22/117, 18.8%) and the lowest in FTLD with
the expansion (6/56, 10.7%), suggesting that the C9orf72 expansion possibly
influences immunological pathways in FTLD.
PMID- 29957386
TI - Long-term outcomes of varicella zoster virus infection-related myelitis in 10
immunocompetent patients.
AB - OBJECTIVE: To describe the clinical presentation and long-term disease outcomes
of varicella zoster virus (VZV) infection-related myelitis (VZVM) in
immunocompetent patients. METHOD: A series of 10 immunocompetent patients with
VZVM were retrospectively observed and followed (3-96 months). RESULTS: The onset
of myelitis was timed in relation to the appearance of VZV-associated rash (-3 to
50 days). Rash locations included the cervical (5), thoracic (2), and lumbar (3)
dermatomes, whereas myelitis localized to the cervical (6) and thoracic (9)
spinal cord and the medulla (1). Spinal MRI revealed extensive longitudinal
transverse myelitis in nine patients, with multiple segmental lesions (>=2
segments) evident in five patients. Aquaporin-4, myelin oligodendrocyte
glycoprotein, ganglioside Q1b, and ganglioside T1b antibodies were detected in
some patients. Three patients fulfilled the 2015 diagnostic criteria for
neuromyelitis optica spectrum disease, of whom two relapsed. Seven patients were
treated with intravenous antivirals and methylprednisolone, with the remaining
three patients receiving methylprednisolone only. Ongoing immunosuppressive
therapy was provided for two patients who experienced relapses. To date, no
patients have reported VZV reactivation. Over the course of follow-up, the
Expanded Disability Status Scale (EDSS) score deceased from 4.9 to 2.6 on
average. CONCLUSIONS: VZVM runs a relatively benign course in immunocompetent
patients, although relapses can occur depending on patient immune status. A
comprehensive evaluation of patient's autoimmune condition is recommended.
PMID- 29957387
TI - Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and
IL-17 and exerts preventive and therapeutic efficacy in rodent experimental
autoimmune neuritis.
AB - Guillain-Barre syndrome (GBS) is an immune-mediated acute disorder of the
peripheral nervous system. Despite treatment, there is an associated mortality
and severe disability in 9 to 17% of the cases. Decitabine (DAC) is a
hypomethylating drug used in myelodisplastic syndrome, that has been shown to
exert immunomodulatory effects. We have evaluated the effects of DAC in two
rodent models of GBS, the Experimental Allergic Neuritis (EAN). Both prophylactic
and therapeutic treatment with DAC ameliorated the clinical course of EAN,
increasing the numbers of thymic regulatory T cells and reducing the production
of proinflammmatory cytokines. Our data suggest the possible use of decitabine
for the treatment of GBS.
PMID- 29957388
TI - Differences in neuroimmune signalling between male and female patients suffering
from knee osteoarthritis.
AB - The primary aim was to identify cytokines involved in blood borne, neuroimmune
joint-to-CNS signalling in knee osteoarthritis (OA) patients. Monocyte
chemoattractant protein 1 (MCP1) and Interleukin-8 (IL-8) were elevated in the
cerebrospinal fluid (CSF) in patients indicating neuroinflammation. Significant
positive correlations were found for MCP1 across CSF, serum and synovial fluid
(SF), in female, but not male patients. The results revealed sex differences in
neuroimmune signalling and implicated MCP1 in blood borne joint-to-CNS signalling
in female patients. Symptom severity correlated with IL-6 and IL-8 levels in SF,
but was inversely associated with IL-6 and IL-8 levels in CSF, indicating that
neuroinflammation in OA may be an adaptive, possibly neuroprotective mechanism
promoting symptom reduction.
PMID- 29957389
TI - Effects of vitamin D on axonal damage during de- and remyelination in the
cuprizone model.
AB - Vitamin D deficiency is a risk factor for multiple sclerosis and associated with
higher disease activity. The aim of this study was to investigate the effects of
cholecalciferol and calcitriol on axonal damage during de- and remyelination in
the cuprizone model. We found significantly less reduction of neurofilament
immunopositive axons in the high vs. low cholecalciferol group, while high dose
calcitriol, given during remyelination, did not influence axonal regeneration.
Our results indicate that high dose vitamin D could protect against axonal loss
in an experimental model for demyelination, if given before and during the
demyelination.
PMID- 29957390
TI - The intrathecal polyspecific antiviral immune response (MRZ reaction): A
potential cerebrospinal fluid marker for multiple sclerosis diagnosis.
AB - We tested the performance of MRZ-reaction, an intrathecal humoral immune response
against-Measles (M), Rubella (R) and Varicella Zoster (Z) viruses, in multiple
sclerosis (MS) diagnosis. The MRZ-reaction was significantly more positive in MS
than in non-MS group with a specificity of 91.9%. In MS group, the RZ-profile was
the most prevalent and the R-specific antibody-index was correlated to the number
of oligoclonal bands (OCB) in CSF. Interestingly, the MRZ-reaction was detected
in 53% of OCB-negative-MS patients. The MRZ-reaction seems to be a relevant CSF
diagnostic marker of MS disease. The likely relation between its positivity and
the vaccination status deserves to be investigated.
PMID- 29957391
TI - Pioglitazone is superior to quetiapine, clozapine and tamoxifen at alleviating
experimental autoimmune encephalomyelitis in mice.
AB - Recent evidence suggests that clozapine and quetiapine (atypical antipsychotics),
tamoxifen (selective-estrogen receptor modulator) and pioglitazone (PPARgamma
agonist) may improve functional recovery in multiple sclerosis (MS). We have
compared the effectiveness of oral administration of these drugs, beginning at
peak disease, at reducing ascending paralysis, motor deficits and demyelination
in mice subjected to experimental autoimmune encephalomyelitis (EAE). Mice were
immunized with an immunogenic peptide corresponding to amino acids 35-55 of the
myelin oligodendrocyte glycoprotein (MOG35-55) in complete Freund's adjuvant and
injected with pertussis toxin to induce EAE. Unlike clozapine, quetiapine and
tamoxifen, administration of pioglitazone beginning at peak disease decreased
both clinical scores and lumbar white matter loss in EAE mice. Using kinematic
gait analysis, we found that pioglitazone also maintained normal movement of the
hip, knee and ankle joints for at least 44 days after MOG35-55 immunization. This
long-lasting preservation of hindleg joint movements was accompanied by reduced
white matter loss, microglial and macrophage activation and the expression of pro
inflammatory genes in the lumbar spinal cords of EAE mice. These results support
clinical findings that suggest pioglitazone may reduce the progressive loss of
motor function in MS by decreasing inflammation and myelin damage.
PMID- 29957392
TI - Different features between pediatric-onset and adult-onset patients who are
seropositive for MOG-IgG: A multicenter study in South China.
AB - BACKGROUND: Immunoglobulin against myelin oligodendrocyte glycoprotein (MOG-IgG)
is a potential demyelinating disease-associated autoantibody. Whether clinical
features of MOG antibody-associated demyelinating diseases change with age
remains unclear. OBJECT: To investigate the different clinical features between
pediatric-onset and adult-onset MOG-IgG-seropositive patients in a relatively
large cohort. METHODS: A total of 816 consecutive patients with suspected
demyelinating disease were prospectively enrolled from three tertiary academic
centers in South China from February 2016 to December 2016. Sixteen pediatric
onset cases (<=14 years old) and 34 adult-onset cases (>14 years old)
seropositive for MOG-IgG were identified. Differences in clinical features
between the two groups were investigated. RESULTS: There was a significant
difference in the cumulative incidence of first relapse among the two groups (P =
.008). Cerebral symptoms were significantly higher in pediatric-onset patients
than in adult-onset patients, either at disease onset (pediatric-onset group,
10/16(62.5%); adult-onset group, 8/34(23.53%); P = .007) or throughout the course
of disease (pediatric-onset group, 11/16(68.8%); adult-onset group, 10/34(29.4%);
P = .009). Optic nerve symptoms were more common in adult-onset groups, but no
significant difference was found between the two groups. A significantly higher
rate of pediatric-onset patients (9/16, 56.3%) met the acute disseminated
encephalomyelitis criteria compared with adult-onset patients (2/34, 5.9%) (P =
.0003), and isolated optic neuritis was mainly diagnosed in adult-onset patients
(pediatric-onset group, 2/16(12.5%); adult-onset group, 14/34(41.2%); P = .043).
The MOG-IgG titer showed a significant positive correlation with total protein
levels in cerebrospinal fluid, but only in adult-onset patients (r = 0.95; P =
.0004). On magnetic resonance imaging, extensive white matter lesions were
observed in both groups, and the number was much higher in pediatric-onset (7/15,
46.7%) than in adult-onset patients (4/29, 13.8%) (P = .043). At the last follow
up, more pediatric-onset patients (10/16, 62.5%) experienced complete recovery
(EDSS 0.0 at last follow up) compared with adult-onset patients (9/34, 26.5%) (P
= .014). CONCLUSIONS: Distinctive features are present between pediatric-onset
and adult-onset patients with MOG-IgG. Further studies are required to determine
the different underlying pathogenesis of MOG antibody at different ages.
PMID- 29957393
TI - GABAergic malfunction in the anterior cingulate cortex underlying maternal immune
activation-induced social deficits.
AB - Social deficits are one of the major symptoms of psychiatric disorders, including
autism spectrum disorders (ASDs) and schizophrenia. However, the underlying
mechanism remains ill-defined. Here, we focused on the anterior cingulate cortex
(ACC), a brain region that is related to social behaviors, of mice that received
poly(I:C)-induced maternal immune activation. Offspring born from poly(I:C)
treated dams exhibited social deficits in a three-chamber task at juvenile
stages. Using whole-cell patch clamp recordings, we found that layer 2/3
pyramidal cells were hyperactive in acute ACC slices prepared from poly(I:C)
treated mice compared to those from saline-treated mice. The hyperexcitation was
associated with a reduction in inhibitory synapse activity. Local injection of
the GABAA receptor enhancer clonazepam into the ACC of poly(I:C)-treated mice
restored the social behaviors of the mice. These results suggest that the
balanced excitability of ACC neurons is essential for social ability.
PMID- 29957394
TI - Myeloid cell responses after spinal cord injury.
AB - The past decade has revealed much about the complexity of the local inflammatory
response after spinal cord injury (SCI). A major challenge is to distinguish
between microglia and monocyte-derived macrophages (MDMs) to determine their
phenotype and function. Transcriptome studies have revealed microglia-selective
genes but are still limited in scope because many markers are downregulated after
injury. Additionally, new genetic reporter mice are available to study microglia
and MDMs. There is more evidence now for the plasticity and heterogeneity of
microglia and MDMs. We also discuss the role of neutrophils that are the first
peripheral cells to enter the injured CNS.
PMID- 29957395
TI - Place and preference effects on the association between mental health and
internal migration within Great Britain.
AB - Individuals with mental health needs are more likely to migrate than the general
population, but the effects of migration preference and place of residence are
often overlooked. These issues are addressed through the application of a novel
origin and destination multilevel model to survey data. In comparison to those
with good mental health, individuals with poor mental health are more likely to
make undesired moves and this is moderated, but not explained by place of
residence. Implications for understanding the mental health and migration
relationship, and its impact on service provision are then proposed.
PMID- 29957396
TI - Health in changing neighborhoods: A study of the relationship between
gentrification and self-rated health in the state of California.
PMID- 29957397
TI - Urban-rural disparity and urban population growth: A multilevel analysis of under
5 mortality in 30 sub-Saharan African countries.
AB - OBJECTIVES: To assess whether country-level urban population growth is associated
with the magnitude of the urban-rural disparity in under-five mortality (U5M)
using ecologic and multilevel analyses. METHODS: We used data from 2010 to 2015
Demographic and Health Surveys and World Bank data from 30 sub-Saharan African
countries (n = 411,054 women). Country-level linear regressions determined
associations between urban population growth and economic growth between 2005 and
2010 on U5M risk differences. Multilevel logistic regression models were used to
determine the impact of urban population growth on the urban advantage in U5M,
adjusting for child and maternal factors. RESULTS: Countries with greater urban
population growth and low economic growth had greater disparities in U5M between
urban and rural areas. After adjusting for known U5M risk factors in multilevel
analyses, interactions between country-level urban population growth and
urbanicity were identified. CONCLUSIONS: Continued efforts to evaluate and
address disparities in child mortality outcomes in sub-Saharan Africa should
acknowledge urbanicity in context, as well as socioeconomic and geographic
realities of families, mothers and children. Low-resource, demographically
shifting environments require novel strategies to decrease child mortality.
PMID- 29957398
TI - Epidemiology of multiple myeloma in Taiwan, a population based study.
AB - BACKGROUND: Although the incidence of multiple myeloma (MM) in Asia is lower than
in Western countries, it is steadily increasing. However, limited data are
available that describe the epidemiology of MM in Asia. METHODS: We conducted a
retrospective cohort study using the Taiwan National Healthcare Insurance
Research database to estimate the disease burden and clinical characteristics of
patients with MM in Taiwan. All newly diagnosed confirmed MM patients during 2007
2012 were enrolled. Patients were followed up until death or end of the
observation period (December 31, 2013), whichever occurred first. RESULTS: A
total of 2723 newly diagnosed MM patients were included in the cohort analysis,
of whom 58.0% (1578/2723) were men. The average age of MM patients was 67.6
years. At the time of diagnosis, the mean Charlson Comorbidity Index was 1.8,
35.3% of patients had anemia, 18.0% had bone fracture, 16.4% had renal disease
and 17.3% had pneumonia. The crude annual incidence of newly diagnosed MM
increased from 1.74 per 100 000 population in 2007 to 2.27 per 100 000 population
in 2012 (p < 0.0001), and the age-adjusted incidence from 1.41 to 1.59 per 100
000 population (p = 0.01). The use of novel treatments expanded over the study
period. The crude and age-adjusted annual MM mortality rate did not change
significantly over time. Case fatality decreased from 25.5% in 2007 to 19.4% in
2012 (p < 0.0001). CONCLUSION: The age-adjusted incidence of MM in Taiwan
increased by 13% between 2007 and 2012. Despite the introduction of new
treatments, MM remains largely incurable with 19.4% mortality.
PMID- 29957399
TI - Ethanol-induced modulation of GPR55 expression in human monocyte-derived
dendritic cells is accompanied by H4K12 acetylation.
AB - Inflammation supports the progression of alcohol-related organ injury. Recent
research findings have linked ethanol exposure to changes in histone acetylation
and deacetylation in the brain and in peripheral tissues, leading to ethanol
dependence related damage. One of the mechanisms that has been shown to play a
major role during inflammation is the cannabinoid system. Previous research has
demonstrated that ethanol can modulate cannabinoid receptors' functions. Our lab
has shown that the G protein-coupled receptor (GPR55), a novel cannabinoid
receptor, is upregulated in binge drinkers and in cells treated acutely with
ethanol. Additionally, our group has also uncovered that chronic ethanol exposure
leads to an increase in histone modifications, such as acetylation. However, the
regulatory mechanism of GPR55 within the immune system under the influence of
ethanol is poorly understood. Since changes in histone modifications might lead
to changes in gene expression, we hypothesize that the mechanism of ethanol
induced upregulation of GPR55 is linked to epigenetic changes on histone
proteins. Taking into account previous findings from our lab, the goal of the
present study was to determine whether there is any relevant association between
histone hyperacetylation and the regulation of the novel cannabinoid receptor
GPR55 in monocyte-derived dendritic cells (MDDCs) of human origin treated acutely
with ethanol. Therefore, monocytes were isolated from buffy coats and allowed to
differentiate into MDDCs. The cells were treated with ethanol for 24 h,
harvested, fixed, and stained with antibodies against GPR55. As expected, based
on previous findings, confocal microscopy showed that ethanol exposure increases
GPR55 expression. In order to demonstrate the correlation between histone
acetylation and GPR55 expression regulation, the cells were treated with ethanol,
harvested, and then the chromatin was extracted and fractionated for chromatin
immunoprecipitation (ChIP) assay, followed by real-time qPCR for the analysis of
DNA fragments. The results showed an enrichment of the histone modification
H4K12ac in the GPR55 gene of MDDCs treated with ethanol. Furthermore, siRNA
against the histone acetyltransferase Tip60 (responsible for the acetylation of
H4K12) resulted in a downregulation of GPR55. In conjunction, these results
indicate that in the presence of ethanol, the upregulation of GPR55 expression is
accompanied by H4K12 acetylation, which might have a significant effect in the
ability of this innate immune system's cells to cope with cellular stress induced
by ethanol. However, the causality of ethanol regulation of H4K12ac in GPR55
expression changes still lacks further elucidation; therefore, additional
experimental approaches to confirm a significant causality between H4K12
acetylation and ethanol regulation of GPR55 are currently undergoing in our lab.
PMID- 29957400
TI - Secondary cytoreductive surgery - viable treatment option in the management of
platinum-sensitive recurrent ovarian cancer.
AB - OBJECTIVE: This study aimed to evaluate the impact of the secondary cytoreductive
surgery on survival parameters in women with platinum-sensitive recurrent ovarian
cancer who undergone secondary cytoreduction following chemotherapy compared to
women who recieved chemotherapy alone. STUDY DESIGN: In a retrospective study,
data were rewieved from women who were diagnosed and treated with ovarian cancer
and its primary platinum-sensitive recurrence at the University Hospital Brno in
the Czech Republic between November 2009 and March 2016. Out of the total number
of 62 patients with recurrence, 30 women underwent cytoreductive surgery plus
chemotherapy and 32 were treated with chemotherapy alone. The good performance
status expressed by ECOG score 0-1, the single site of recurrence regardless of
platinum-free interval or multiple sites of recurrence but no carcinomatosis and
platinum-free interval >12 months, and no or small-volume ascites (<500 ml) were
considered inclusion criteria for cytoreductive surgery. Women not meeting these
criteria were treated by chemotherapy alone. Descriptive statistics, Kaplan-Meier
survival curves and Log-Rank test were used for statistical estimations. RESULTS:
The analysis confirmed more favorable prognosis in patient group treated with a
combination secondary cytoreduction and chemotherapy. Mean disease-free survival
(DFS) was 49.8 months (95% CI; 33.2-66.3) and mean overall survival (OS) stood at
54.0 months (95% CI; 39.4-68.6) in this patient cohort, while in patient group
treated with chemotherapy alone it was found that mean DFS was 16.6 months (95%
CI; 7.4-25.8) and mean OS stood at 26.2 months (95% CI; 16.6-35.8). When testing
the difference between survival curves, statistically significant differences
were observed in both DFS (p = 0.010) and OS (p = 0.007) rates between two
treatment groups. Age < 60 years at the time of recurrence and zero macroscopic
residual disease after secondary cytoreduction were identified as favorable
prognostic factors for both DFS and OS in a multivariate analysis. CONCLUSION:
Secondary cytoreductive surgery is acceptable as a viable treatment option for
highly selected women with ovarian cancer recurrence. Complete resection is
considered ultimate goal of secondary cytoreduction on condition that the balance
between maximal survival gain and minimal operative morbidity will be kept.
PMID- 29957401
TI - The addition of growth hormone adjuvant therapy to the long down regulation
protocol in poor responders undergoing in vitro fertilization: Randomized control
trial.
AB - OBJECTIVE: to detect the impact of growth hormone (GH) co-treatment to the long
down regulation protocol, on the outcomes of IVF/ICSI cycles in poor responders.
STUDY DESIGN: this parallel open label randomized control trial was conducted in
a university hospital. It included 240 females satisfying the bologna criteria
for poor responders. The enrolled females were randomized into 2 groups: A
(long/GH) receiving GH adjuvant therapy to the long protocol and group B
(control) receiving the long protocol alone. The main outcome measure was the
live birth rate (fresh, frozen and cumulative). RESULTS: GH supplementation
improved the number of collected oocytes (5.4 +/- 1.7 vs. 4.3 +/- 2.1), MII
oocytes (4.1 +/- 2.1 vs. 2.1 +/- 1.4), fertilized oocytes (4.0 +/- 2.2 vs. 2.0 +/
1.2), transferred embryos (2.4 +/- 0.9 vs. 1.6 +/- 1.1) and cryopreserved (0.5
+/- 0.7 vs. 0.2 +/- 0.5). There was no significant difference in the live birth
rate whether fresh (17.5% vs. 14.1%) or cumulative (18.3% vs. 14.7%).
CONCLUSIONS: Further studies are needed to know the true impact of adding GH to
the induction protocols in poor responders, as there was no difference in the
live birth rates between the study groups, indicating a lack of trend toward
benefit from GH supplementation in poor responders. CLINICAL TRIAL REGISTRATION:
NCT02338206.
PMID- 29957402
TI - Potential of Trichoderma koningii to eliminate alachlor in the presence of copper
ions.
AB - The filamentous fungus Trichoderma koningii is capable of fast and effective
eliminate alachlor (90% after 72 h when added separately and 80-60% in the
presence of 1-5 mM of copper). After 168 h over 99% elimination of alachlor
resulted in detoxification and was connected with the mitigation of reactive
oxygen species (ROS) production. Using MS/MS techniques, seven dechlorinated and
hydroxylated metabolites were identified. Cytochrome P450 and laccase participate
in biotransformation of the herbicide by this non-ligninolytic fungus. Laccase
activity is stimulated both by copper and the mixture of copper and alachlor,
which seems to be important for combined pollutants. T. koningii is characterized
by high tolerance to copper (up to 7.5 mM). The metal content in mycelia reached
0.9-7.76 mg in 1 g of dry biomass. Our results suggest that T. koningii strain
seems to be a promising tool for bioremediation of agricultural areas co
contaminated with copper-based fungicides and chloroacetanilide herbicides.
PMID- 29957403
TI - Novel method for in situ investigation into graphene quantum dots effects on the
adsorption of nitrated polycyclic aromatic hydrocarbons by crop leaf surfaces.
AB - Nitrated polycyclic aromatic hydrocarbons (NPAHs) are PAH derivatives with more
toxic effects to ecosystem, and the partitioning of NPAHs in crop system
constitutes the potential exposure to human health through the dietary pathway.
In the present study, a novel method for in situ detection of 9-nitroanthracene
(9-NAnt) and 3-nitrofluoranthene (3-NFla) adsorbed onto the leaf surfaces of
living soybean and maize seedlings was established based on the fiber-optic
fluorimetry combined with graphene quantum dots (GQDs) as a fluorescent probe.
The detection limits for the in situ quantification of the two adsorbed NPAHs
ranged from 0.8 to 1.6 ng/spot (spot represents determination unit, 0.28 cm2 per
spot). Using the novel method, the effects of GQDs on the adsorption of
individual 9-NAnt and 3-NFla by the living soybean and maize leaf surfaces were
in situ investigated. The presence of GQDs altered the adsorption mechanism from
the sole film diffusion to the combination of film diffusion and intra-particle
diffusion, and shortened the time required to achieving adsorption equilibrium by
15.8-21.7%. Significant inter-species and inter-chemical variability existed in
terms of the equilibrated adsorption capacity (qe) with the sequence of soybean >
maize and 3-NFla > 9-NAnt. The occurrence of GQDs enlarged the qe values of 9
NAnt and 3-NFla by 22.8% versus 28.7% for soybean, and 16.2% versus 20.3% for
maize, respectively, which was largely attributed to GQDs-induced expansion to
the surface area for adsorbing NPHAs and the stronger electrostatic interaction
between the -NO2 of NPAH molecules and the functional groups (e.g., -COOH, -OH)
of GQDs outer surfaces. And, the varied enhancement degrees in the order of 3
NFla > 9-NAnt might be explained by the steric effects that resulted in the
easier accessibility of -NO2 of 3-NFla to the outer surface of GQDs. Summarily,
the GQDs increased the retention of NPAHs on crop leaf surfaces, potentially
threatening the crop security.
PMID- 29957404
TI - Quantitative structure-property relationship (QSPR) models for predicting the
physicochemical properties of polychlorinated biphenyls (PCBs) using deep belief
network.
AB - Octanol/water partition coefficient (log P), octanol/air partition coefficient
(log KOA) and bioconcentration factor (log BCF) are important physiochemical
properties of organic substances. Quantitative structure-property relationship
(QSPR) models are a promising alternative method of reducing and replacing
experimental steps in determination of log P, log KOA and log BCF. In the current
study, we propose a new QSPR model based on a deep belief network (DBN) to
predict the physicochemical properties of polychlorinated biphenyls (PCBs). The
prediction accuracy of the proposed model was compared to the results of previous
reported models. The predictive ability of the DBN model, validated with a test
set, is clearly superior to the other models. All results showed that the
proposed model is robust and satisfactory, and can effectively predict the
physiochemical properties of PCBs without highly reliable experimental values.
PMID- 29957405
TI - Adsorption of boron by CA@KH-550@EPH@NMDG (CKEN) with biomass carbonaceous
aerogels as substrate.
AB - This research reports an innovative boron adsorbent of CA@KH-550@EPH@NMDG (CKEN)
via the modification of N-methyl-d-glucosamine (NMDG) on the surface of biomass
carbonaceous aerogel, which is environmentally friendly, economically
inexpensive, has simple preparation process and good regenerability. SEM and FT
IR characterization results indicate that CKEN has a 3D cross-staggered structure
with lots of hydroxyl groups and pore structure, which are beneficial to the
diffusion of boron and the chelation interaction between boron and CKEN. The
adsorption behavior of CKEN for boron was evaluated. Various parameters affecting
adsorption properties, viz., pH, ionic strength, initial concentration of boron,
temperature and contact time were investigated. The adsorption kinetics is fitted
with pseudo-second-order kinetics model better and the adsorption of boron on
CKEN is an exothermic process. The adsorption equilibrium reached within 15 h
with the maximum adsorption amount of 1.42 mmol/g (298 K). Moreover, CKEN also
showed excellent reusability by consecutive five cycles of adsorption-desorption.
It can be used as a potential recyclable adsorbent for efficient enrichment of
boron from aqueous solution.
PMID- 29957406
TI - Room-temperature fabrication of bismuth oxybromide/oxyiodide photocatalyst and
efficient degradation of phenolic pollutants under visible light.
AB - Bismuth oxybromide/oxyiodide (Bi4O5BrxI2-x) photocatalysts were successfully
fabricated using a facile homogeneous precipitation method at room temperature.
The obtained Bi4O5BrxI2-x demonstrated highly enhanced visible-light performances
compared with Bi4O5Br2 and Bi4O5I2. The poducts were characterized by X-ray
diffraction (XRD), UV-vis diffuse reflectance spectra (DRS), X-ray photoelectron
spectroscopy (XPS), scanning electron microscope (SEM), and transmission electron
microscope (TEM). The DRS analysis shows that the band gap structures of
Bi4O5BrxI2-x have been gradually modulated by changing the Br/I molar ratio. The
obtained Bi4O5BrxI2-x samples have exhibited efficient photocatalytic activities
in decomposing resorcinol, o-phenylphenol, and 4-tert-butylphenol. The Br/I molar
ratio has great influence on the activity of the photocatalysts, and
Bi4O5Br0.6I1.4 exhibited the best activity which was about 2.77 and 1.80 times
higher than that of Bi4O5Br2 and Bi4O5I2, respectively. The degradation
intermediates were identified by liquid chromatography-mass spectrometry (LCMS),
and the possible degradation pathway of resorcinol over Bi4O5BrxI2-x
photocatalysts was proposed. The strong visible light absorption, high charge
separation efficiency, and proper band potentials should be responsible for the
excellent activity of Bi4O5BrxI2-x photocatalyst. Trapping experiments using
radical scavengers confirmed the generation of O2-, OH, and h+, but only O2- and
h+ have played the chief role in removing organic pollutants from water.
PMID- 29957407
TI - Effects of pipe material on nitrogen transformation, microbial communities and
functional genes in raw water transportation.
AB - Raw water transportation pipelines are vital in an urban water supply system for
transporting raw water to drinking water treatment plants. This study
investigated the effects of pipe material on nitrogen transformation, microbial
communities and characteristics of related function genes in paint-lined steel
pipe (PLSP) and cement-lined steel pipe (CLSP) raw water model systems. We
established quantitative relationships between specific functional genes and
change rates of nitrogen pollutants, which were verified by field investigation
on nitrogen pollutant transformations in real raw water transportation systems.
The results showed that the CLSP produced higher ammonia nitrogen (NH4+-N)
transformation rates and higher effluent concentrations of nitrate nitrogen (NO3-
N) and dissolved organic nitrogen (DON) than the PLSP. Both pipes achieved high
and stable nitrite nitrogen (NO2--N) and low total nitrogen (TN) removal
efficiency. Nitrification was found to be the dominant process in both model
systems, especially in the CLSP. Characteristics of microbial communities and
nitrogen functional genes, which were analysed by high-throughput pyrosequencing
and quantitative polymerase chain reaction (qPCR), respectively, varied between
the two pipe systems. Nitrogen transformation pathways, identified by path
analysis, were also different between the PLSP and CLSP due to different
microbial community characteristics and synergistic effects of nitrogen
functional genes. In the CLSP, (NH4+-N->NO2--N) with part denitrification, was
the primary transformation pathway of ammonia nitrogen (NH4+-N), while only
ammonia oxidization contributed to NH4+-N transformation in the PLSP. (NO2--N
>NO3--N) was the main pathway involved in NO2--N transformation and NO3--N
accumulation. The TN removal showed complex relationships with nitrification,
denitrification and nitrogen fixation processes. These findings provided
molecular-level insights into nitrogen pollutant transformations during the
transportation of raw water through different types of pipes and technical
support for the selection of raw water pipe materials. In our study area, the
Taihu basin, China, PLSP was better than CLSP for distributing raw water in a
short transportation distance, due to the lower effluent concentrations of DON
and NO3--N and less abundance of microorganisms.
PMID- 29957408
TI - Development of vestibular behaviors in zebrafish.
AB - Most animals orient their bodies with respect to gravity to facilitate locomotion
and perception. The neural circuits responsible for these orienting movements
have long served as a model to address fundamental questions in systems
neuroscience. Though postural control is vital, we know little about development
of either balance reflexes or the neural circuitry that produces them. Recent
work in a genetically and optically accessible vertebrate, the larval zebrafish,
has begun to reveal the mechanisms by which such vestibular behaviors and
circuits come to function. Here we highlight recent work that leverages the
particular advantages of the larval zebrafish to illuminate mechanisms of
postural development, the role of sensation for balance circuit development, and
the organization of developing vestibular circuits. Further, we frame open
questions regarding the developmental mechanisms for functional circuit assembly
and maturation where studying the zebrafish vestibular system is likely to open
new frontiers.
PMID- 29957409
TI - Theoretical studies for the infrared spectra of Ar-CO2 complex: Fundamental and
combination bands.
AB - Two potential energy surfaces (PESs) were constructed for the ground and excited
states of Ar-CO2 complex at the rigid rotor approximation. Besides the notable T
shape structure, two equivalent linear structures were also found on the PES for
the first time. Based on the PESs of ground and excited states, the bound state
calculations were performed to determine the rotational energy levels for the
ground and excited states. In combination of the experimental spectroscopic
parameters of ground state and the differences of rotational energy levels, we
give a theoretical prediction of infrared spectra including one fundamental band
and two combination bands for two isotopomers Ar-12C16O2 and Ar-12C18O2 in the
nu3 region of CO2 monomer. The predicted transition frequencies and spectroscopic
parameters of excited states are in excellent agreement with the available
experimental data, and these results can also be used as a guide to perform the
further investigation for the infrared spectra of combination bands
experimentally.
PMID- 29957411
TI - Molecular structure, spectroscopic, dielectric and thermal study, nonlinear
optical properties, natural bond orbital, HOMO-LUMO and molecular docking
analysis of (C6Cl2O4) (C10H14N2F)2.2H2O.
AB - A new chloranilate compound with 1-(2-fluorophenyl)piperazine has been
synthesized and characterized using spectroscopic methods and X-ray diffraction.
The atomic arrangement can be described by an H-bonded 3D network, formed by
anionic entities, organic cations and H2O molecules linked together via NH...O,
OH...Cl, CH...Cl and CH...O hydrogen bonds. The vibrational absorption bands of
the various characteristic groups of this compound have been identified by
infrared spectroscopy. Moreover, the thermal and dielectric analyses have shown
that the title compound has a phase transition at 393 K. The surface mapped over
the dnorm property, highlights the A?H (AO, C, Cl and F) as the main
intermolecular contacts. On the other hand, the geometry, intermolecular bonds
and harmonic vibrational frequencies of the title molecule have been investigated
using the B3LYP/6-31G (d, p) method. The stability of the structure obtained, as
well as the charge transfer within the molecule, have been confirmed by
determining the energies of the HOMO and LUMO levels and the theoretical gap
energy. Molecular docking studies of the title compound have also been conducted
as part of this study.
PMID- 29957410
TI - Photophysical properties and biological evaluation of a Zinc(II)-5-methyl-1H
pyrazole Schiff base complex.
AB - A new ZnL2 complex containing two molecules of a tridentate Schiff base derived
from 5-methyl-1H-pyrazole (HL) is synthesized and characterized. The
photophysical properties of HL and ZnL2 are disclosed and supported by CAMB3LYP
DFT/TDDFT calculations. It is shown that there is keto-tautomer stabilization
upon excitation with an energetically accessible triplet state in HL, not present
in ZnL2, this explaining the differences found in the emissions of the compounds.
The intrinsic fluorescence of ZnL2 is used as probe for a detailed study of its
binding to human serum albumin. The protein-complex association is
thermodynamically favourable and it is shown by fluorescence quenching and time
resolved analysis that the fluorescence quenching involves a mixed mechanism with
prevalence of static quenching, which corroborates adduct formation at site I,
close to the Trp214 residue. The ability of ZnL2 to bind DNA was also evaluated,
as well as its cytotoxic activity against MCF7 (breast), PC3 (prostate) cancer
cells and hamster V79 fibroblasts. ZnL2 is a moderate DNA intercalator (Kapp =
3.9 * 104 M-1) and depicts a quite low IC50 value at 48 h against MCF7 cells
(IC50 = 530 nM), but much higher for PC3 and V79 cells. The relevance of a more
careful speciation evaluation of ZnL2 and other potential metal-based drugs in
incubation media used in in vitro tests is highlighted.
PMID- 29957412
TI - Influence of different ancillary ligand on the phosphorescent properties of
platinum(II) complexes.
AB - In past two decades, lots of bidentate Pt(II) complexes are developed as
potential organic light emitting diodes due to their simple synthetic process.
The relative low quantum efficiency is one of the major blocks for their
applications. Two new heteroleptic Pt(II) complexes bearing an n-hexyloxy
substituted phenyllepidine-based ligand and either a picolinate (pic) (1) or
acetylacetonate (acac) (2) ancillary ligand are synthesized as orange-red-emitter
by Wawrzinek and coauthors. The quantum efficiency of 2 is much larger than that
of 1 indicating that the variation of ancillary ligand has a great effect on the
performance. Inspired by it, other two new bidentate Pt(II) complexes are
theoretically designed with the same primary ligand along with pyrazolone (pzl)
(3) or N-substituted carbazole (NCaz) (4) ancillary ligand. The phosphorescent
properties are explored by density functional theory (DFT) and time dependent DFT
(TDDFT) methods with the ultimate goal to explore the influence of ancillary
ligand. Moreover, the emission rule is confirmed. Finally, the quantum yield is
estimated according to the radiative rate constant (kr) and nonradiative rate
constant (knr). The smaller knr is the vital item to determine the high quantum
yield.
PMID- 29957413
TI - Adsorption of Celecoxib on B12N12 fullerene: Spectroscopic and DFT/TD-DFT study.
AB - In this study, we evaluated the effect of the Celecoxib (CXB) adsorption on the
electronic and optical properties of B12N12 fullerene by using density functional
theory (DFT) and time-dependent density functional theory (TD-DFT) calculations
with the M06-2X functional and the 6-311+G** basis set. The calculated adsorption
energies of CXB with the B12N12 fullerene was evaluated at T = 298.15 K in the
vacuum and solvent (water) environments with the M06-2X functional. UV absorption
and IR spectra were calculated and studied in order to identify the most
important changes happening as a consequence of interactions between CXB and
B12N12 fullerene. The results revealed that the adsorption of the CXB molecule
from its NH2 head on the B12N12 is more favorable than those of the SO2 and NH
groups in the gas and solvent environments. It is anticipated that the applied
B12N12 fullerene could be suitable as a biomedical carrier for the delivery of
CXB drug.
PMID- 29957414
TI - Random initialisation of the excitation-emission matrix fluorescence spectral
variables in constraint fashion for subsequent multivariate curve resolution
alternating least square analysis on a peculiarly designed calibration set:
Simultaneous sensing of nine polycyclic aromatic hydrocarbons in water samples.
AB - Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and mutagenic in nature
therefore their sensing in water sample is an important analytical task. In the
present work, a novel approach that is based on the random initialisation of the
excitation-emission matrix fluorescence (EEMF) spectral variables in constraint
fashion for subsequent multivariate curve resolution alternating least Square
(MCR-ALS) analysis is introduced for simultaneously sensing the complex dilute
aqueous mixture of PAHs. The usefulness of the proposed analytical approach is
successfully demonstrated by applying it intentionally on a calibration set that
is peculiar in many senses. The peculiarity mainly arises because the designed
(i) the calibration set consist of nine PAHS having significant spectral overlap,
(ii) the concentration of each PAH in different samples are kept constant and
(iii) any two samples differ only in the presence and absence of the PAHs. The
proposed approach is found to make precise and accurate estimation of each of the
nine PAHs without involving any pre-separation. In summary, the proposed approach
provides a simple and cost-effective procedure for simultaneous sensing of
several PAHs in water samples. The proposed approach could be very useful in
developing countries.
PMID- 29957415
TI - Reactivity of CO on Ni4 cluster- effect of spin multiplicity and H doping-A DFT
investigation.
AB - We investigated the reactivity of carbon monoxide on tetrahedral Ni4 clusters at
different spin multiplicity applying density functional theory calculations
considering pure and hybrid functional. The stability of the clusters increases
with the increasing spin multiplicity and doping hydrogen in Ni4 cluster. The
adsorption or binding energy of CO on Ni4 cluster is thermodynamically feasible
process at normal condition whereas dissociation is not feasible. Ab initio
molecular orbital analysis shows the orbital overlaps are observed at bridging
site, three fold sites, and tetra coordinated centre and formation of delta-bond
in the cluster. In NBO analysis, CO binds strongly to the Ni4 cluster not only by
two NiC bond (spd hybrid), but also donor-acceptor delocalization interactions,
for example, sigma type BD(CO) -> BD*(NiC) and BD(NiC) -> BD*(NiC/CO), two pi
type BD(CO) -> LP*(Ni) and several diffuse RY*(C) <- LP(Ni) and pi*(CO) <- LP(Ni)
interactions. Singlet Ni4 cluster shows highest activation energy barrier, 3 eV.
H-doped Ni4 cluster decreases dissociation barrier and favors CH bond formation.
PMID- 29957416
TI - Process bioengineering applied to BTEX degradation in microaerobic treatment
systems.
AB - The effect of different microaeration flow rates and dosing points, and of
effluent recirculation, on microaerobic BTEX degradation in an anaerobic
bioreactor was assessed. Additionally, a sensitivity and recovery analysis for
this system was performed during microaeration failure simulations. Under
anaerobic conditions, BTEX removal efficiencies between 55 and 82% were achieved
depending on the compound, being benzene the most recalcitrant one. Microaeration
(0.5-2.0 mL air min-1) ensured high removal efficiencies (>83%) for all
compounds, and the best results were obtained for the flow rate of 1.0 mL air min
1, particularly for benzene, with a 30% increase in its removal efficiency.
Effluent recirculation showed to be an important factor to improve mass transfer
and, consequently, BTEX removal. Volatilization was negligible even under
microaerobic conditions, suggesting that microbial activity was the main removal
mechanism. Finally, after microaeration shutdown periods, the bioreactor could
recover its prior performance within up to 2 days.
PMID- 29957417
TI - Quantitative assessment of wildfire risk in oil facilities.
AB - Despite frequent occurrence of wildfires around the world, the role of wildfires
has rarely been taken into account in risk assessment of process plants in
wildlands, especially that large inventory of flammable petroleum products in
contact with the heat of wildfire can lead to severe domino effects. We have
developed a dynamic risk assessment framework by integrating available models of
fire spread and domino effect analysis with online maps of wildfire
characteristics such as ignition probability and heat intensity to investigate
the impact of wildfires on oil facilities. The framework is modular, so one can
readily enhance its accuracy by replacing the current techniques with more
sophisticated ones. The application of the methodology is demonstrated on an oil
terminal.
PMID- 29957418
TI - Effects of population density of a village and town system on the transportation
cost for a biomass combined heat and power plant.
AB - Combined heat and power (CHP) generation can meet winter heating demands.
Therefore, biomass CHP plants are more suitable for the development of biomass
energy in village and town systems in cold regions. Transportation cost is one of
the factors that determine operating costs. In this study, potential biomass
energy is estimated based on the distribution of various types of crops. The
locations and service areas of biomass CHP plants are determined using geographic
information system analysis tools based on population distribution and energy
demand data. Equations that contain multiple interference factors are used to
calculate the raw material supply area and transportation cost for a biomass CHP
plant to generate an optimal transportation route within a region. The analysis
results show that biomass CHP plants are only suitable for village and town
systems with a relatively low population density (PD). The curve of the supply
area versus the PD of the village and town system (PDVTS) has an inverse-S shape.
The transportation cost increases exponentially as the PDVTS increases. Biomass
CHP plants can achieve higher efficiency in transportation costs when built in
areas with a PDVTS <= 65 people/km2.
PMID- 29957419
TI - Hazardous aluminum dross characterization and recycling strategies: A critical
review.
AB - By finding appropriate recycling approaches, the volume of wastes, corresponding
disposal cost, and the pollution of environment could be diminished. Also, such
promising approaches can result in the conservation of natural sources and
economic benefits. Aluminum dross as a hazardous solid waste in aluminum
production industries has caused serious environmental and public health
challenges. Various methods have been introduced for management, utilization, and
recycling of the waste. The present review describes, firstly, different types of
aluminum dross, their environmental and health hazards, composition, and
production process and then focuses on the direct and indirect recycling
approaches and recovery strategies.
PMID- 29957420
TI - Deep injection and the potential of biochar to reduce fumigant emissions and
effects on nematode control.
AB - Reducing fumigant emissions is essential for minimizing the environmental impacts
of pre-plant soil fumigation. Low permeability plastic films are effective at
reducing emissions but have high initial purchase, installation, and disposal
costs. The objective of this study was to evaluate if deep fumigant injection and
biochar soil amendments can reduce emissions, improve fumigant distribution in
soil, and provide acceptable control of plant parasitic nematodes. A pre-plant
soil fumigation trial was conducted in a commercial orchard in the San Joaquin
Valley, CA, USA. Treatments included two rates of Telone(r) C-35 (a mixture of
1,3-dichloropropene and chloropicrin) under totally impermeable film or with no
surface seal, two injection depths (45 or 65 cm), and two biochar rates (20 or 40
ton ha-1). Emission rates were generally low due to rain events encountered
during the trial, but data clearly showed that the deep injection enhanced
fumigant delivery to depths below 60 cm and resulted in significantly lower peak
emission compared to the standard injection depth. Biochar applied at 40 ton ha-1
had the lowest emission rates during 1-month monitoring period. Although
variability in nematode survival was high, tarped, deep injection, and biochar
treatment showed lower survival of nematodes at various depths. Increase in
fumigant persistence, especially chloropicrin, was observed in this study, likely
due to the high soil moisture and low temperature. All data indicate that biochar
amendments can help reduce fumigant emissions without reducing nematode control;
however, additional research is needed to optimize treatments, determine the
affordability of various biochar materials, and validate results under a range of
field conditions.
PMID- 29957421
TI - Public perception towards river and water conservation practices: Opportunities
for implementing urban stormwater management practices.
AB - The effectiveness of urban stormwater management practices (SMPs) on local water
quality is dependent on adoption rates reaching a critical mass. While numerous
studies have measured the effectiveness of practices on controlling water
quantity and improving water quality, few have focused on the perspective of the
public. The purpose of this study was to identify individuals' perceptions of
urban SMPs implementation in the public and private realms, and how longitudinal
perceptions about the local river could inform future water resource management.
Through the lens of environmental behavior theories, we performed statistical
analyses on four surveys - 2006, 2009, 2014 and 2016 - administered to urban
residents in the Wabash River watershed in Tippecanoe County, Indiana. Our
findings show that residents' water quality awareness and sense of personal
responsibility increase over the ten years studied. In particular, rain garden
adopters have higher appreciation of the Wabash River and care about how the
river functions than other SMP adopters and non-adopters. In terms of urban SMP
adoption, results indicate that residents are supportive of integrating rain
barrels and rain gardens into public spaces. Perceptions of SMP benefits related
to functional benefits, rather than environmental benefits, are prevalent when
considering implementing SMPs on personal property. In addition, respondents
support reducing stormwater charges for adopters of such practices on private
property. Although cognitive barriers exist in those who have yet to adopt the
practices, including concerns about SMP effectiveness, maintenance, aesthetics,
and risk of bugs and insects, adopters are less likely to perceive such barriers.
This research suggests that making resources (i.e., skills, knowledge, equipment,
funding) more accessible to the public is essential, but not sufficient to
encourage pro-environmental behaviors. Promoting public involvement in watershed
activities, increasing their awareness about how urban SMPs function, and
emphasizing the functional benefits of practices can be effective in motivating
adoption.
PMID- 29957422
TI - Properties of seawater neutralized bauxite residues and changes in chemical,
physical and microbial properties induced by additions of gypsum and organic
matter.
AB - Seawater neutralization is a technique that can be used to treat bauxite residue
prior to its storage but, as yet, no attempts have been made to revegetate it.
Seawater neutralized bauxite residue was found to have a pH1:5 of 9.3 and to be
highly saline (EC1.5 16.5 dS m-1). After leaching pH1:5 rose to 9.7 and the
residue was still highly sodic (ESP = 64-69%). Addition of 1% gypsum, prior to
leaching, arrested this increase in pH while with 5% gypsum addition the pH1:5
was lowered to 8.9. Addition of 5% gypsum also reduced ESP to 38% and increased
watercress germination in the residue from 58% in control treatments to 88%. The
major ions in leachates were Na+ and Cl- and gypsum application increased the
quantities of Na+, Ca2+ and SO42- leached. Addition of 6% biosolids or 6% poultry
manure added exchangeable cations to the mud and lowered ESP by 5-11%.The EC was
2.8-3.7 (mean 3.1) times higher and pH 0.2-0.7 (mean 0.43) units lower in
saturation paste compared with 1:5 soil:water extracts. Addition of amendments
had only small effects on physical properties. While organic C content was
increased more by biosolids than poultry manure addition the reverse was the case
for soluble organic C, microbial biomass C and basal respiration. It was
concluded that although seawater neutralization initially lowers the pH of
bauxite residues it is unlikely to increase the ease with which they can be
revegetated.
PMID- 29957423
TI - Acute whole-body vibration increases reciprocal inhibition.
AB - Based on previous evidence that whole-body vibration (WBV) affects pathways
involved in disynaptic reciprocal inhibition (DRI), the present hypothesis-driven
experiment aimed to assess the acute effects of WBV on DRI and co-contraction.
DRI from ankle dorsiflexors to plantar flexors was investigated during submaximal
dorsiflexion before and after 1 min of WBV. With electromyography, musculus
soleus (SOL) H-reflex depression following a conditioning stimulation of the
peroneal nerve (1.1x motor threshold for the musculus tibialis anterior, TA) was
assessed and co-contraction was calculated. After WBV, DRI was significantly
increased (+4%, p < 0.05). SOL (-13%, p < 0.05) and TA (-6%, p < 0.05) activities
were significantly reduced; co-contraction tended to be diminished (-8%, p =
0.05). Dorsiflexion torque remained unchanged. After WBV, DRI increased during
submaximal isometric contraction in healthy subjects. The simultaneous SOL
relaxation and TA contraction indicate that a more economic movement execution is
of functional significance for WBV application in clinical and athletic
treatment.
PMID- 29957425
TI - Adsorption of nicotine in aqueous solution by a defective graphene oxide.
AB - Extensive concerns have been focused on the emerging contaminants including
nicotine in the aquatic system recently. Graphene oxide (GO) and modified
graphene oxides (GO-COOH and defective GO-COOH) are used as effective adsorbents
to remove nicotine from aqueous solution. The adsorption isotherms and kinetics
of the adsorbents all fit well with Langmuir model and pseudo-second-order model,
respectively. The thermodynamic studies show that the adsorption is an exothermic
and spontaneous process. The influence of pH and ionic solution strength on the
adsorbents is also investigated. The maximum adsorption capacity can be observed
at pH value of ca. 8. The adsorption capacities of nicotine are decreased upon
the increase of sodium ion concentration. Among all the adsorbents, the defective
GO-COOH adsorbents possess the maximum adsorption capacity of nicotine of 196.5
mg g-1 obtained from Langmuir isotherm. In regeneration experiments, the
defective GO-COOH adsorbents can maintain 95.1% of adsorption capacity after five
times of cyclic adsorption-desorption processes. The adsorbents are identified by
Fourier transform infrared, 13C solid-state magic-angle spinning nuclear magnetic
resonance, X-ray photoelectron and Raman spectroscopies to determine the
adsorption mechanisms and structure on the adsorbents. It can be deduced that the
surpassing performance of defective GO-COOH may be ascribed to the unique
adsorption mechanism of defects, the enhanced pi-pi interaction and cation-pi
bonding. The highly-efficient and stable features enable the defective GO-COOH a
promising adsorbent to eliminate nicotine from water.
PMID- 29957424
TI - Variability in coordination patterns in children with developmental coordination
disorder (DCD).
AB - High motor variability is an often-found characteristic of Developmental
Coordination Disorder (DCD). Still, the role of high motor variability in DCD
needs further examination. This study focused on variability in coordination
patterns, which is essential considering that DCD is a coordination disorder. We
examined variability in coordination patterns of the arm over repetitions of
trials in goal-directed reaching movements. This variability was partitioned into
variability that does not affect the index fingertip position (Vucm) and
variability that does affect the index fingertip position (Vort). This study
aimed to increase the understanding of motor variability in DCD by comparing Vucm
and Vort between children with DCD and typically developing (TD) children in a
goal-directed reaching task. Twenty-two children (eleven with DCD) ages 6-11
performed 30 reaching movements. The Uncontrolled Manifold method was used to
quantify Vucm and Vort. Results showed that children with DCD had more Vucm than
TD children while Vort was similar between groups, showing that coordination
patterns in children with DCD are more variable, but interestingly, this higher
variability does not affect performance. This study indicates that high motor
variability in DCD is not necessarily negative. Possible roles of motor
variability in DCD are discussed.
PMID- 29957426
TI - Spatial distribution, bioaccumulation profiles and risk for consumption of edible
bivalves: a comparison among razor clam, Manila clam and cockles in the Venice
Lagoon.
AB - Despite their ecological and economical relevance, a lack of data is still
occurring about the distribution, abundance, bioaccumulation and risks for
consumption of some edible bivalves. The present study has been carried out in
the Venice Lagoon taking into account three bivalve species to investigate i) the
possible relationship among the biological features-distribution, abundance and
bioaccumulation patterns- of razor clams (Solen marginatus Pulteney, 1799),
Manila clams (Ruditapes philippinarum Adams and Reeve, 1850) and lagoon cockles
(Cerastoderma glaucum Poiret, 1789) and the hydrological features, namely
sediment physico-chemical characteristics and contamination; ii) their specific
role as bioindicators of inorganic contamination; iii) the possible risks for
human health associated with the consumption of these edible bivalves. Results
showed that species distribution and abundance, especially for razor clams, was
mainly influenced by environmental conditions and sediment granulometric
composition, above metal(loid) contamination. The contamination patterns were
different among species, as Manila clam generally showed higher bioaccumulation
values for most of the metal(loid)s, whilst lagoon cockles preferentially
accumulated Ni. Eventually, a serious concern exists for the human consumption,
for all species and investigated sites regarding As. This study will raise
attention on the effects of bioaccumulation of inorganic pollutants by edible
bivalves and risks for consumers' safety, especially concerning razor clams and
cockles, for which a critical lack of data on metal(loid) bioaccumulation occurs
from the Northern Adriatic Sea.
PMID- 29957427
TI - Management and research strategies of karst aquifers in Greece: Literature
overview and exemplification based on hydrodynamic modelling and vulnerability
assessment of a strategic karst aquifer.
AB - Karst aquifers are valuable water resources in terms of quantity and quality,
hence, their protection and rational management is of utmost importance to
sustain water supply. An overview of research articles regarding Karst aquifers
in Greece was obtained revealing that progressively the initial simple
statistical analysis was replaced from advanced tools but rarely coupled.
Additionally, a combined approach including the concept of groundwater
vulnerability and pollution risk in conjunction with statistical and hydrodynamic
analysis was performed in the complex karst aquifer of Damasi-Titanos in Thessaly
Central Greece. The karst aquifer discharges via three springs and it is in
dynamic interaction with one of the two rivers that cross the system. The water
demands of the area are mainly met with groundwater from the karst aquifer
rendering its protection fundamental priority for the sustainability of the area.
The hydrodynamic analysis of the karst system was performed by pairing
statistical techniques and KarstMod. The analysis revealed a high correlation
between the springs that highlights the karstification maturity of the aquifer.
Additionally, spring discharge is mainly controlled by the percolation of River
Titarisios rather than precipitation. Following the hydrodynamic analysis, the
PaPRIKa method was applied and validated using sensitivity analysis in order to
assess the intrinsic vulnerability. The vulnerability and hazard maps were
combined to produce the pollution risk map of the karst aquifer. The majority of
the karst aquifer is characterized by high to very high vulnerability as well as
pollution risk. The case study and the obtained overview revealed that a holistic
approach can provide mutually supported results increasing their reliability. In
this base, a four-step road map including hydrogeological observation,
statistical analysis, modelling and vulnerability assessment is suggested in
order to obtain the sustainable exploration and integrated management of karst
aquifers in Greece.
PMID- 29957428
TI - Incorporating vegetation dynamics noticeably improved performance of hydrological
model under vegetation greening.
AB - Numerous hydrological models calculate actual evaporation as a function of
potential evaporation (PET) and soil moisture stress. There are some limitations
for such empirical equations since they do not consider vegetation changes, and
therefore cannot account for the different responses of soil evaporation and
plant transpiration to changes in environmental factors and cannot be used for
evaluating the impacts of vegetation changes. Here, we investigated whether
incorporating a physically based evaporation scheme into a grid-based
hydrological model can improve the accuracy of hydrological simulations. The
original and modified hydrological models were evaluated in a basin which has
experienced rapid vegetation greening. The model evaluations were performed using
streamflow observations, soil moisture observations and water balance-based
evaporation estimates. Results indicated that the modified model can provide
better evaporation simulations than the original model during the period of
vegetation greening. The streamflow and soil moisture simulations by the modified
model over the same period benefitted significantly from the improvement in
evaporation simulations and exhibited better consistency with in situ
observations than the original model. This study underscores the importance of
including vegetation change information in evaporation estimates and demonstrated
that the physically based evaporation equation can be used in hydrological models
to improve the hydrological simulations under vegetation greening conditions.
PMID- 29957430
TI - Dissolved carbon transport in a river-lake continuum: A case study in a
subtropical watershed, USA.
AB - Rivers and lakes have been traditionally studied as separate entities for carbon
transport. However, there is a gap in our knowledge of the connectivity of
dissolved carbon in a river-lake continuum. In this study, we analyzed dissolved
carbon along the Little River-Catahoula Lake in subtropical Louisiana, United
States to assess carbon biogeochemistry in such a river-lake continuum. Monthly
in-situ measurements and water sample collections were made at four locations
during April 2015 to February 2016 to determine riverine carbon transport into
and out of the lake. Results show that much of the dissolved inorganic carbon
(DIC) in the river-lake continuum originated from 13C depleted sources with an
average delta13CDIC of -18.50/00. Significant decreases in DIC were found after
the river passed through the lake (from 482 to 399 MUmol L-1), which was most
prevalent when the lake was not affected by backwater flow from the downstream
river. CO2 outgassing could be mainly responsible for the sink behavior of the
lake for DIC. Dissolved organic carbon (DOC) in the studied watershed were mostly
terrigenous with low delta13CDOC averaged at -29.20/00. Significant, consistent
decreases in DOC concentrations were found from the river to the lake inflow and
then to the lake outflow. During the majority of the year, the lake reduced DOC
concentrations from the river inflow water, but switched to functioning as a
source of DOC during warmer, dryer conditions in September and October due to
increased water residence time. Therefore, the lake functioned both as a sink and
as a source for DOC.
PMID- 29957429
TI - Optimization of methane-dependent oxygenic denitrification in sequencing batch
reactors by insights into the microbial interactions.
AB - Methane-dependent oxygenic denitrification (O2DN) is a promising technology used
for reducing greenhouse gas emissions of nitrous oxide (N2O) during wastewater
treatment. Heterotrophic bacteria are associated with methane-dependent O2DN
bacteria, and it has been proposed that metabolic cross-feeding occurs between
the two populations above. In this study, a mathematical model was developed to
describe the microbial processes and interactions between methane-dependent O2DN
bacteria and associated heterotrophic bacteria in a sequencing batch reactor
(SBR). A growth factor-dependent decoupling of metabolism and growth of methane
dependent O2DN bacteria was introduced into the model. Effects of influent
substrates, operating parameters, and initial biomass on microbial community and
reactor performance were then investigated, and the above parameters were
optimized using the model. Results surprisingly show that organic matter in the
influent greatly stimulated the growth of methane-dependent O2DN bacteria but
slightly limited the increase of heterotrophic bacteria. This effect could be
explained by the increased excretion of growth factors by heterotrophic bacteria
and the intensified competition for nitrite when methane-dependent O2DN bacteria
increased. These results will assist in providing a new understanding of
microbial interactions in methane-dependent O2DN systems and offer a new and
efficient strategy for operating methane-dependent O2DN reactors.
PMID- 29957431
TI - Pharmaceuticals, hormones, pesticides, and other bioactive contaminants in water,
sediment, and tissue from Rocky Mountain National Park, 2012-2013.
AB - Pharmaceuticals, hormones, pesticides, and other bioactive contaminants (BCs) are
commonly detected in surface water and bed sediment in urban and suburban areas,
but these contaminants are understudied in remote locations. In Rocky Mountain
National Park (RMNP), Colorado, USA, BCs may threaten the reproductive success
and survival of native aquatic species, benthic communities, and pelagic food
webs. In 2012-2013, 67 water, 57 sediment, 63 fish, 10 frog, and 12 quality
control samples (8 water and 4 sediment) were collected from 20 sites in RMNP.
Samples were analyzed for 369 parameters including 149 pharmaceuticals, 22
hormones, 137 pesticides, and 61 other chemicals or conditions to provide a
representative assessment of BC occurrence within RMNP. Results indicate that BCs
were detected in water and/or sediment from both remote and more accessible
locations in RMNP. The most commonly detected BCs in water were caffeine,
camphor, para-cresol, and DEET; and the most commonly detected BCs in sediment
were indole, 3-methyl-1H-indole, para-cresol, and 2,6-dimethyl-naphthalene. Some
detected contaminants, including carbaryl, caffeine, and oxycodone, are clearly
attributable to direct local human input, whereas others may be transported into
the park atmospherically (e.g., atrazine) or have local natural sources (e.g.,
para-cresol). One or more pharmaceuticals were detected in at least 1 sample from
15 of 20 sites. Most of the 29 detected pharmaceuticals are excreted primarily in
human urine, not feces. Elevated net estrogenicity was observed in 18% of water
samples, and elevated vitellogenin in blood was observed in 12% of male trout,
both evidence of potential endocrine disruption. Hormone concentrations in
sediment tended to be greater than concentrations in water. Most BCs were
observed at concentrations below those not expected to pose adverse effects to
aquatic life. Results indicate that even in remote locations aquatic wildlife can
be exposed to pharmaceuticals, hormones, pesticides, and other bioactive
contaminants.
PMID- 29957432
TI - System based on thermal control of the HCCI technology developed for reduction of
the vehicle NOX emissions in order to fulfil the future standard Euro 7.
AB - On the present the environmental protection belongs among the most important
worldwide priorities. From this reason there is valid within the framework of the
European Union the standard Euro, which is specifically defined in the transport
area. Nowadays the actual issue of this standard is signed Euro 6. It is
established in order to eliminate most of the undesirable air pollutants.
However, there is already prepared a new and even stricter emission standard Euro
7. It is a well-known fact that the actual emission standards are very hard and
the automobile factories, together with the engine design concepts are trying to
fulfil the new emission standards, mainly the NOX emission requirements. These
circumstances also caused the infamous affair "dieselgate". The new engine
concept, which is called HCCI (Homogeneous Charge Compression Ignition), could be
a suitable solution of the present NOX emission problems. Principle of the HCCI
technology is based on self-ignition of the homogenous fuel mixture using
compression in order to reduce emissions, whereas the NOX emission level is
almost negligible. However, there are also several essential problems connected
with the above-mentioned innovative technology, for example a high level of
pressures arising during the compression process and intensive heat release.
Another serious problem is a complicated control of the self-ignition process.
This article presents an original technical solution, which enables to regulate
the whole self-ignition process and in this way to ensure a reliable operation of
the HCCI engine. We would like to emphasize also a fact that this unique solution
was applied for a patent, as well. The innovated piston combustion engine was
installed in the experimental vehicle designed for participation at the
international competition shell eco marathon 2018 in London focused on
minimisation of the fuel consumption.
PMID- 29957433
TI - The effects of marine farm-scale sequentially integrated multi-trophic
aquaculture systems on microbial community composition, prevalence of sulfonamide
resistant bacteria and sulfonamide resistance gene sul1.
AB - Aquaculture, one of the most important food production practices worldwide, faces
serious challenges of mitigating the detrimental impacts of intensive farming on
the environment and increased prevalence of antibiotic resistance. To develop an
environment-friendly aquaculture system, a land-based and farm-scale sequentially
integrated multi-trophic aquaculture (IMTA) system was established for farming
Chanos chanos in southwestern Taiwan. In this system, fishes are cultured in
combination with organic extractive shellfish and inorganic extractive seaweed.
This study aimed to evaluate the prevalence of sulfonamide-resistant bacteria,
microbial community structure, and occurrence of sulfonamide resistance genes in
the IMTA and traditional aquaculture systems. Water and sediment samples were
collected before raising and after harvesting C. chanos. Our results showed that
the occurrence of sulfonamide-resistant phenotypes in the IMTA system was
comparable with that in influent seawater, while the traditional system exhibited
a high sulfonamide resistance rate. Additionally, the traditional system resulted
in a deviation of the bacterial community structure from that of seawater. In the
water samples from the IMTA system and influent seawater, Proteobacteria and
Bacteroidetes were the two dominant phyla, representing approximately 75% and 15%
of the community, respectively. In the traditional system, Actinobacteria,
constituting 39% of the community, was the dominant bacterial phylum. Thirty-one
sulfonamide-resistant bacterial species were isolated. In conclusion, a
sequentially IMTA system showed superior ability to maintain the prevalence of
antibiotic resistance and the integrity of the bacterial community structure
compared to the traditional farming system, representing a potentially valuable
aquaculture system for preserving the sustainability of the marine environment.
PMID- 29957434
TI - Simulation on different response characteristics of aerosol particle number
concentration and mass concentration to emission changes over mainland China.
AB - : In this study, Nested Air Quality Prediction Modeling System with Advance
Particle Microphysics module (NAQPMS+APM) is applied to simulate the response
characteristics of aerosol particle number concentration and mass concentration
to emission changes over mainland China. It is the first attempt to investigate
the response of both aerosol mass concentration and number concentration to
emission changes using a chemical transport model with detailed aerosol
microphysics over mainland China. Results indicate that the response
characteristics are obviously different between aerosol particle number
concentration and mass concentration. Generally, the response of number
concentration shows a more heterogeneous spatial distribution than that of mass
concentration. Furthermore, number concentration has a higher sensitivity not
only to primary particles emission but also to precursor gases than that of mass
concentration. Aerosol particle mass concentration exhibits a consistent trend
with the emission change and yet aerosol number concentration does not. Due to
the nonlinearity of aerosol microphysical processes, reduction of primary
particles emission does not necessarily lead to an obvious decrease of aerosol
number concentration and it even increases the aerosol number concentration. Over
Central-Eastern China (CEC), the most polluted regions in China, reducing primary
particles emission rather than precursor gas emissions is more effective in
reducing particles number concentration. By contrast, the opposite is true over
the northwestern China. The features of fine particles pollution revealed in this
study are associated with the spatial differences in China's population,
geography, climate and economy. Considering the more adverse effects of ultrafine
particles on human health and the spatial distribution of population, making
different measures in controlling particles number concentration from that
controlling mass concentration in different regions over mainland China is
indicated. MAIN FINDINGS: FPN concentration responds more heterogeneously to
emission than FPM. Spatial difference of response of FPN to emission is
distinguished by a boundary line.
PMID- 29957435
TI - Exploring various ligand classes for the efficient sequestration of stannous
cations in the environment.
AB - Metal pollution, coming from both natural and anthropogenic sources, has become
one of the most serious environmental problems. Various strategies have been
tested with the aim of removing heavy metals from environment. In this
contribution, containing a robust experimental work together with a critical
literature analysis, the sequestering ability of a variety of ligands towards
Sn2+ cation will be evaluated in the conditions of several natural fluids, i.e.
sea water, fresh water, human blood plasma, urine and saliva. 13 structural and
11 thermodynamic descriptors will be selected for a total of thirty-eight
molecules belonging to different classes (carboxylic acids, amines, amino acids,
phosphonates, polyelectrolytes etc. ...). For the filling of those missing data
relative to the 11 thermodynamic descriptors, different strategies will be
adopted, including simple correlations and Nipals algorithm. The evaluation of
the sequestering ability of the ligands is assessed in terms of estimation of
pL0.5 (total concentration of ligand required to bind the 50% of metal in
solution), an empirical parameter that takes into account all the side reactions
in solutions and does not depend on the speciation scheme. Partial least square
calculations were performed to model the pL0.5 and to determine its correlation
with the abovementioned descriptors. The possibility to design and build up new
tailor-made molecules capable of effectively sequester Sn2+ in various conditions
is crucial for practical applications in biosphere, hydrosphere and lithosphere.
PMID- 29957436
TI - Prevalence of Legionella in retirement homes and group homes water distribution
systems.
AB - BACKGROUND: Although historically the focus has been placed above all on hospital
infections and travel-associated outbreaks, most of the cases of Legionella
infection are sporadic and occur in community-dwellers. OBJECTIVES: To evaluate
the presence and load of Legionella in hot water systems of non-healthcare
facilities that host closed communities. Furthermore, we tried to verify the
association between Heterotrophic Plate Counts (HPCs) and presence of Legionella.
METHODS: We collected hot water and biofilm samples from the showerheads of
retirement homes and group homes. Samples were tested by culture method for the
presence of Legionella. Confirmation and identification were carried out through
Latex test and PCR. We determined the HPCs at 22 and 37 degrees C by the pour
plate method. Statistics performed through STATA. RESULTS: We collected 140 hot
water and biofilm samples, 95 from 26 retirement homes and 35 from 9 group homes.
Legionella was found in 36.8% samples collected from retirement homes and only in
10.3% group homes' samples (p = 0.01). Legionella was identified more frequently
in water than in biofilm (29.8% vs 16.9%); just in one case the pathogen was
found in the biofilm only. L. pneumophila sg 1 was the pathogen more frequently
isolated (65.8%), with an average load of 2720 CFU/L (SD = 8393 CFU/L). We have
often noticed a high microbial contamination (67% of HPCs >200 CFU/mL) and
identified a higher prevalence of Legionella for intermediate values of HPC 22
degrees C (p = 0.011). 32% of people hosted in retirement homes were exposed to
Legionella. CONCLUSIONS: Colonization of water-systems of retirement homes and
group homes is anything but occasional, and in our survey it mainly affects the
former, moreover often due to L. pneumophila sg 1. The search for the pathogen in
the biofilm has proved to be of little use. The relationship between HPC and
Legionella deserves further studies.
PMID- 29957437
TI - Air pollution deposition on a roadside vegetation barrier in a Mediterranean
environment: Combined effect of evergreen shrub species and planting density.
AB - Leaf deposition of PM10-100, PM2.5-10, PM0.2-2.5 and of 21 elements was
investigated in a roadside vegetation barrier formed by i) two evergreen shrub
species (Photinia * fraseri, Viburnum lucidum), with ii) two planting densities
(0.5, 1.0 plant m-2), at iii) three distances from the road (2.0, 5.5, 9.0 m), at
iv) two heights from the ground (1.5, 3.0 m), and on v) three dates (Aug, Sep,
Oct). The presence of black and brown on-leaf PM10-100 and their element
composition were detected by microscopy and image analysis. Pollutant deposition
was also measured using passive samplers at five distances from the road (2.0,
5.5, 9.0, 12.5, 19.5 m) in the area of the barrier and in an adjacent lawn area.
V. lucidum had more PM2.5-10 and PM0.2-2.5 on leaves than P. * fraseri, while
most elements were higher in P. * fraseri. Most pollutants decreased at
increasing distances from the road and were higher at 1.5 m from the ground
compared to 3.0 m. Higher planting density in P. * fraseri enhanced the
deposition of PM10-100 and PM2.5-10, while in V. lucidum, the planting density
did not affect the depositions. Black PM10-100 decreased a long distance from the
road and was entirely composed of carbon and oxygen, which was thus identified as
black carbon from fuel combustion. The vegetation barrier had a higher deposition
of most PM fractions at 5.5-12.5 m, while in the lawn area, depositions did not
change. At 19.5 m, the PM10-100 was 32% lower behind the barrier than in the lawn
area. In conclusion, the vegetation barrier changed the deposition dynamics of
pollutants compared to the lawn area. These results strengthen the role of
vegetation barriers and shrub species against air pollution and may offer
interesting insights for the use of new road green infrastructures to improve air
quality.
PMID- 29957438
TI - Patterns of land change and their potential impacts on land surface temperature
change in Yangon, Myanmar.
AB - This study used remote sensing imagery to characterize land use/cover patterns
and to derive land surface temperature (LST) of Greater Yangon, the largest urban
agglomeration in Myanmar, to provide insights into the association between land
use/cover and seasonal, daytime, and nighttime LST change. Analysis of Landsat
images from 1987 to 2015 showed urban expansion radiating from the city center
and along prominent rivers, with major increases in built-up land (6.4%) and
grassland (10.1%) and consequent decline in agricultural land (17%). Examination
of MODIS LST showed that agricultural land was warmer than the city core during
daytime in hot seasons, while in cold seasons, the city core was warmer than its
rural surroundings during both daytime and nighttime. Correlation analysis
revealed stronger association between built-up land and nighttime LST from 2000
to 2015, suggesting an increased surface urban heat island effect. Furthermore,
this study highlighted two main differences from prior work on the influences of
land use/cover on LST. First, the predominant land use/cover type that had great
overall impact on LST was agricultural land, marked by its statistically
significant correlation coefficients across all time periods of analysis. Such
finding emphasized the influence of agriculture and related practices on the
atmosphere and climate system. Second, the temporal analysis of LST highlighted a
stronger and more complicated role water played because of its negative
correlations with daytime LST and positive correlations with nighttime LST. The
findings of this study underscored more complex effects of land use/cover on the
spatial and temporal variations of LST in Yangon, compared to prior work that
generally reported high LST in the urban areas. These insights improve the
understanding of the land change consequences on the temporal dynamics of LST and
can support sustainable land use planning for the better well-being of the
inhabitants in Greater Yangon.
PMID- 29957439
TI - Correlations between mobile phone use and other risky behaviours while riding a
motorcycle.
AB - Motorcyclist safety is a major concern in many developing countries.
Understanding motorcycle riders' risky behaviours, particularly among the younger
population, is essential to developing effective interventions. This paper
explores the correlations between mobile phone use while riding and other risky
riding behaviours as well as the relationships between perceived risks and risky
riding behaviours, using an online survey of university students in Vietnam.
Results show that calling while riding a motorcycle had the highest prevalence
(74%) while reckless overtaking had the lowest prevalence (33.2%). Survey
participants who indicated that they had the behaviours of reckless overtaking or
riding on sidewalks were around twice as likely to call, text, or search for
information while riding. In addition, those who admitted that they rode a
motorcycle while under the influence of alcohol were nearly twice as likely to
call or text while riding. The results also show that perceived crash risks
reduced the likelihood of risky riding behaviours, including calling, texting,
searching for information, speeding, running red lights, riding on the wrong side
of a road, and riding on sidewalks. A more coordinated approach to enforcement is
needed to help reduce the prevalence of multiple risk taking behaviours among
motorcyclists.
PMID- 29957440
TI - A case of de novo NAA10 mutation presenting with eyelid myoclonias (AKA Jeavons
syndrome).
PMID- 29957441
TI - Comparison of lamotrigine and oxcarbazepine monotherapy for pediatric focal
epilepsy: An observational study.
AB - PURPOSE: Oxcarbazepine is known as an effective first-line monotherapy for
pediatric focal epilepsy. Lamotrigine has also been reported to have similar
efficacy to and better tolerability than carbamazepine. Therefore, the
effectiveness of oxcarbazepine and lamotrigine monotherapies was compared in
patients with pediatric focal epilepsy. METHOD: A total of 116 patients in
pediatric patients with partial epilepsy received lamotrigine (n = 43) or
oxcarbazepine (n = 73) monotherapy. The clinical characteristics, seizure
outcomes, reasons for drug discontinuation, retention rate and adverse effects
were evaluated for each drug. RESULTS: Oxcarbazepine was more commonly used than
lamotrigine (69/73 vs. 23/43) as initial monotherapy. Lamotrigine showed better
efficacy than oxcarbazepine in terms of the seizure outcome more than 12 months
(P<0.05). Oxcarbazepine and lamotrigine showed similar tolerability in terms of
the retention rate, drug discontinuation and adverse effects. The rates of
successful discontinuation were similar for patients receiving these drug as
initial monotherapy (P > 0.05). The seizure outcome was much better for
lamotrigine than for oxcarbazepine in patients with normal MRI findings and
normal development (P = 0.001, P = 0.01). The retention rate was high in patients
with MRI abnormalities or developmental delay in the lamotrigine group. The
choice of lamotrigine was the only independent variable that predicted a seizure
free state, even after correcting for clinical variables (OR = 4.80, P = 0.013).
CONCLUSIONS: Lamotrigine was superior to oxcarbazepine monotherapy because of its
greater effectiveness in treating pediatric focal epilepsy. Lamotrigine can be
selected as a first-line monotherapy in patients with or without abnormal MRI
findings or delayed development.
PMID- 29957442
TI - Increased plasma Interleukin-1beta level is associated with memory deficits in
type 2 diabetic patients with mild cognitive impairment.
AB - Type 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI) are both
chronic inflammatory diseases. We aimed to investigate the association of plasma
Interleukin-1beta (IL-1beta) levels with the risk of MCI in T2DM patients. We
divided recruited T2DM patients into two groups, MCI group and healthy-cognition
controls, according to Montreal Cognitive Assessment (MoCA) scores. Demographic
characteristics, clinical parameters and neuropsychological tests were examined.
We recruited 202 T2DM patients in this study, including 94 MCI and 108 healthy
cognition controls. T2DM patients with MCI exhibited increased plasma IL-1beta
and decreased amyloid-beta 42 (Abeta42) levels compared to the controls (all p <
0.05). After adjusting fasting blood glucose (FBG), glycosylated hemoglobin
(HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR) and
Abeta42, plasma IL-1beta levels were negatively correlated with MoCA and AVLT
delayed recall scores, which represented memory function. Multivariable logistic
regression model showed that high plasma IL-1beta level and low plasma Abeta42
level were correlated with increased risk for MCI in T2DM patients. Increased
plasma IL-1beta level was significantly associated with MCI in T2DM patients,
especially memory deficits. Our findings will provide additional insights into
the inflammation pathogenesis of cognitive impairments in T2DM.
PMID- 29957443
TI - Mitochondrial ROS direct the differentiation of murine pluripotent P19 cells.
AB - ROS are frequently associated with deleterious effects caused by oxidative
stress. Despite the harmful effects of non-specific oxidation, ROS also function
as signal transduction molecules that regulate various biological processes,
including stem cell proliferation and differentiation. Here we show that
mitochondrial ROS level determines cell fate during differentiation of the
pluripotent stem cell line P19. As stem cells in general, P19 cells are
characterized by a low respiration activity, accompanied by a low level of ROS
formation. Nevertheless, we found that P19 cells contain fully assembled
mitochondrial electron transport chain supercomplexes (respirasomes), suggesting
that low respiration activity may serve as a protective mechanism against ROS.
Upon elevated mitochondrial ROS formation, the proliferative potential of P19
cells is decreased due to longer S phase of the cell cycle. Our data show that
besides being harmful, mitochondrial ROS production regulates the differentiation
potential of P19 cells: elevated mitochondrial ROS level favours trophoblast
differentiation, whereas preventing neuron differentiation. Therefore, our
results suggest that mitochondrial ROS level serves as an important factor that
directs differentiation towards certain cell types while preventing others.
PMID- 29957444
TI - Tissue preservation in extreme temperatures for rapid response to military
deaths.
AB - Many deployable forensic capabilities, including those used by the Australian
Defense Force (ADF), employ mobile battery-operated fridge/freezers for DNA
sample preservation that are not suitable for rapid response application due to
their size and weight. These fridge/freezers are expensive, require regular
specialised maintenance, and have a set payload. A variety of transport media are
successful preservatives for DNA samples, however, there is no research
specifically targeted to their suitability for operational environments where
temperatures exceed 50 degrees C. This research examined whether sodium chloride
(NaCl), ethanol, and dimethyl sulfoxide (DMSO) could preserve muscle and bone
samples (fresh and early decomposition) as effectively as refrigeration, when
stored at 21 degrees C, 45 degrees C, 55 degrees C, and 65 degrees C for at
least one week. A total of 78 muscle and 78 bone samples were collected from an
unknown deceased individual. Half of each tissue type was stored at 30 degrees C
for 48 h to induce early decomposition. Following this, samples were stored in
the transport media for one week at the above temperatures, and a control set of
samples were refrigerated (-4 degrees C) without any transport media. Preserved
samples would need to provide DNA profiles comparable to the refrigerated samples
for the transport media to be considered a successful replacement method. NaCl
and 70% ethanol preserved muscle samples (fresh and decomposed) up to 65 degrees
C, as well as 70% ethanol and 20% DMSO for fresh bone samples. These results were
comparable with refrigeration and therefore, these preservatives could be used in
rapid response operations by the military and for disaster victim identification.
Conversely, under the conditions of this study, 20% DMSO and 70% ethanol failed
to consistently produce full DNA profiles from decomposed bone, and NaCl
performed poorly at preserving DNA from fresh and decomposed bone samples.
PMID- 29957445
TI - Engineering of RiPP pathways for the production of artificial peptides bearing
various non-proteinogenic structures.
AB - Peptides bearing non-proteinogenic structures characteristic of natural products
have great potential as leads of pharmaceuticals. In the biosynthetic pathways of
ribosomally synthesized and post-translationally modified peptides (RiPPs), the
non-proteinogenic structures are generated by enzymatic structural modification
on precursor peptides encoded in genetic information. The plasticity of this
pathway, in which alterations of the precursor genes directly resulted in
variation of the products by the process of modularly functioning enzymes, have
greatly facilitated both in vivo and in vitro engineering of the pathways. Here,
we review several examples of the synthesis of artificial peptides having non
proteinogenic structures by genetic engineering of RiPP pathways.
PMID- 29957446
TI - High-velocity micro-particle impact on gelatin and synthetic hydrogel.
AB - The high-velocity impact response of gelatin and synthetic hydrogel samples is
investigated using a laser-based microballistic platform for launching and
imaging supersonic micro-particles. The micro-particles are monitored during
impact and penetration into the gels using a high-speed multi-frame camera that
can record up to 16 images with nanosecond time resolution. The trajectories are
compared with a Poncelet model for particle penetration, demonstrating good
agreement between experiments and the model for impact in gelatin. The model is
further validated on a synthetic hydrogel and the applicability of the results is
discussed. We find the strength resistance parameter in the Poncelet model to be
two orders of magnitude higher than in macroscopic experiments at comparable
impact velocities. The results open prospects for testing high-rate behavior of
soft materials on the microscale and for guiding the design of drug delivery
methods using accelerated microparticles.
PMID- 29957447
TI - Evaluation of the micro-mechanical and bioactive properties of bioactive glass
dental porcelain composite.
AB - The aim of this study was to evaluate microhardness and elastic modulus of a
novel sol-gel derived dental ceramic - 58S bioactive glass composite (BP67:
Bioactive Glass:33.3%, Dental Ceramic:66.7%) BP671 material by micro-indentation
and to investigate its microstructure and bioactivity. The research hypotheses
were that the values of microhardness (1) and elastic modulus (2) of the novel
bioceramic composite and the commercial dental ceramic will be of the same order.
The experimental sol-gel derived ceramics showed similar microstructural
characteristics to a commercial feldspathic porcelain, and presence of additional
calcium phosphate phases, which contributed its bioactivity. The formation of an
apatite-like layer on the materials' surface observed by Fourier Transform
Infrared (FTIR)2 spectroscopy, X-ray Diffraction (XRD)3 and Scanning Electron
Microscopy-Energy Dispersive Spectroscopy (SEM-EDS)4 techniques after 12 days of
maintenance in Conventional Simulated Body Fluid (cSBF)5 solution. The BP67
exhibited values of microhardness and modulus of elasticity which were not
statistically significant different compared to dental ceramic, indicating the
adequate mechanical integrity of the material. The results of this study suggest
that the novel bioactive composite could be potentially applied in prosthetic
dentistry, while its thermal and optical properties should be investigated in
future studies.
PMID- 29957449
TI - Remembering Dr. T. Berry Brazelton.
PMID- 29957448
TI - Multisensory integration, body representation and hyperactivity of the immune
system.
AB - Multisensory stimuli are integrated over a delimited window of temporal
asynchronies. This window is highly variable across individuals, but the origins
of this variability are still not clear. We hypothesized that immune system
functioning could partially account for this variability. In two experiments, we
investigated the relationship between key aspects of multisensory integration in
allergic participants and healthy controls. First, we tested the temporal
constraint of multisensory integration, as measured by the temporal binding
window. Second, we tested multisensory body representation, as indexed by the
Rubber Hand Illusion (RHI). Results showed that allergic participants have a
narrower temporal binding window and are less susceptible to the RHI than healthy
controls. Overall, we provide evidence linking multisensory integration processes
and the activity of the immune system. The present findings are discussed within
the context of the effect of immune molecules on the brain mechanisms enabling
multisensory integration and multisensory body representation.
PMID- 29957450
TI - Bullying: What the PNP Needs to Know.
AB - Despite generations of doubt about the true impact of bullying, it is now clear
that childhood bullying can have significant lifelong consequences for victims
and bullies alike. Recent school shootings and suicides by students who have been
victims of bullying have helped to solidify public awareness of the gravity of
the problem of childhood bullying. Adults who were frequently bullied in
childhood have an increased frequency of psychiatric disorders, including
anxiety, depression, and suicidality, extending into middle age (Arseneault,
2017). In fact, frequent bullying in childhood may impact victims similar to
experiencing multiple adverse childhood experiences (Takizawa, Maughan, &
Arseneault, 2014). Bullying also has a detrimental effect on young perpetrators
(Zuckerman, 2016). Bullying is clearly a pediatric health care problem. This
continuing education article will explore bullying in terms of definitions,
epidemiology, types, risk factors, resilience factors, consequences, and
implications for practice.
PMID- 29957451
TI - S.M.A.R.T. Transitions: A Program Evaluation.
AB - INTRODUCTION: Various programs have been proposed to facilitate more successful
transitions from pediatric to adult care for children with special health care
needs. Few have been evaluated for their effectiveness. The purpose of this
project was to systematically evaluate the Duke Complex Care Clinic using the
social-ecological model of adolescent and young adult readiness for transition
(SMART). METHODS: Cross-sectional data were acquired from surveys of 23
patient/parent dyads and from retrospective chart reviews for 50 patients. After
the initial program evaluation, a pilot transition readiness tracking tool was
implemented. RESULTS: Documentation of compliance with the SMART domains was
high. Despite high satisfaction with the clinic and a focus on transition, many
of the patient/parent dyads expressed low confidence in their ability to
transition successfully. CONCLUSIONS: Transition beliefs and expectations should
be further assessed and addressed in transition care visits. Further modification
of the patient tracking tool and clinic flow may improve patient transition
outcomes.
PMID- 29957452
TI - Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1
Deletion Mutations in Patients with Acute Lymphoblastic Leukemia.
AB - Intragenic deletion of IKZF1 is a recurrent genomic alteration in acute
lymphoblastic leukemia. The deletions are mediated by illegitimate
variable(diversity)joining recombination via cryptic recombination signal
sequences (RSSs). We developed a fluorescence in situ hybridization (FISH) probe
set that can detect any type of IKZF1 deletion, including the commonly deleted
exon 4 to 7 region. The probe set consists of a designed probe for the commonly
deleted region (Cy3; red) and a bacterial artificial chromosomes clone probe for
detecting the 3' flanking region (Spectrum Green). Intact IKZF1 showed a fusion
signal, and the deleted allele showed loss of the red signal (0R1G1F). The FISH
probes worked correctly for human leukemic cell lines and clinical samples. One
case showed an atypical break-apart signal (1R1G1F). Inverse PCR of the case
revealed rearrangement of the excised IKZF1 fragment into a legitimate RSS site
at Ig kappa on chromosome 2, suggesting a pathogenic role of this recombination
activating gene 1/2-mediated event. In this study, we established FISH probe
detecting IKZF1 deletion in a quick, quantitative, and cost-effective manner, and
the results provided a novel insight into B-cell receptor editing by
rearrangement of a cryptic RSS-mediated genomic fragment in acute lymphoblastic
leukemia pathology.
PMID- 29957453
TI - Bizarre calcaneal spur: A case report.
AB - INTRODUCTION: A calcaneal spur, also known as enthesophyte, is an abnormal bone
outgrowth at the inferior part of the calcaneus, which is the most common site of
bony spur occurrence. Although there is consensus that a calcaneal spur is a
common cause of heel pain, approximately 20% of calcaneal spurs are asymptomatic
and its pathology remains not fully understood. PRESENTATION OF CASE: In this
report, we present a rare case of a very large and bizarre calcaneal spur in a
young adult man. The calcaneal spur was painful, which affected his foot function
and was associated with plantar fasciitis. The spur length was measured in the
radiograph and exhibited the longest calcaneal spur reported in the literature.
The patient was treated conservatively, and he fully recovered his foot function.
DISCUSSION: This case was unique because although the patient presented with an
extremely large unilateral calcaneal spur, he was young and did not have any
chronic disease; hence, he was treated conservatively. The pain subsided and he
regained full function of his foot. This case questions the association between
calcaneal spur length and plantar fasciitis symptoms. CONCLUSION: This case
confirms that the length of calcaneal spurs, even extremely long ones, is not
associated with the pathology of plantar fasciitis and that surgical treatment is
not necessary.
PMID- 29957454
TI - Magnetic resonance imaging contrast enhancement in vitro and in vivo by
octanuclear iron-oxo cluster-based agents.
AB - A water-soluble octanuclear cluster, [Fe8], was studied with regard to its
properties as a potential contrast enhancing agent in magnetic resonance imaging
(MRI) in magnetic fields of 1.3, 7.2 and 11.9 T and was shown to have transverse
relaxivities r2 = 4.01, 10.09 and 15.83 mM s-1, respectively. A related
hydrophobic [Fe8] cluster conjugated with 5 kDa hyaluronic acid (HA) was
characterized by 57Fe-Mossbauer and MALDI-TOF mass spectroscopy, and was
evaluated in aqueous solutions in vitro with regard to its contrast enhancing
properties [r2 = 3.65 mM s-1 (1.3 T), 26.20 mM s-1 (7.2 T) and 52.18 mM s-1 (11.9
T)], its in vitro cellular cytotoxicity towards A-549 cells and COS-7 cells and
its in vivo enhancement of T2-weighted images (4.7 T) of a human breast cancer
xenografted on a nude mouse. The physiologically compatible [Fe8]-HA conjugate
was i.v. injected to the tumor-bearing mouse, resulting in observable,
heterogeneous signal change within the tumor, evident 15 min after injection and
persisting for approximately 30 min. Both molecular [Fe8] and its HA-conjugate
show a strong magnetic field dependence on r2, rendering them promising platforms
for the further development of T2 MRI contrast agents in high and ultrahigh
magnetic fields.
PMID- 29957455
TI - The impact of dietary consistency on structural craniofacial components:
Temporomandibular joint/condyle, condylar cartilage, alveolar bone and
periodontal ligament. A systematic review and meta-analysis in experimental in
vivo research.
AB - OBJECTIVE: The aim of this systematic review was to provide a comprehensive
synthesis of available evidence evaluating the effect of dietary loading on
temporomandibular joint/condyle, condylar cartilage, alveolar bone of the
mandible and the periodontal ligament in healthy mice and rats. DESIGN: Medline
via PubMed, EMBASE and Open Grey databases were searched for published and
unpublished literature. Search terms included "mandiblular condyle", "alveolar
bone", "temporomandibular joint", "condylar cartilage", "periodontal ligament",
"rat", "mice". After data extraction, risk of bias (SYRCLE) and reporting quality
(ARRIVE) were assessed. Random effects meta-analyses were performed for the
outcomes of interest where applicable. RESULTS: A total of 33 relevant articles
were considered in the systematic review, while only 6 studies were included in
the quantitative synthesis. Risk of Bias in all studies was judged to be unclear
to high overall, while reporting quality was suboptimal. Comparing soft to hard
diet animals, significantly reduced anteroposterior condylar length (4 studies,
weighted mean difference: -0.40 mm; 95% CI: -0.47, -0.32; p < 0.001) and width (4
studies, weighted mean difference: -0.043 mm; 95% CI: -0.51, -0.36; p < 0.001)
were found in rats. Decreased anteroposterior condylar dimensions were detected
for mice as well (2 studies, weighted mean difference: -0.049; 95% CI: -0.56,
0.43; p < 0.001). CONCLUSIONS: Overall, there was strong evidence to suggest a
significant effect of soft diet on reduced condylar dimensions in rodents;
however, there is need for further high quality experimental studies to inform
current knowledge on condylar cartilage, alveolar bone and periodontal ligament
related outcomes.
PMID- 29957456
TI - Effects of anterior tooth crown inclination on occlusal relationship-A study in
three-dimensional reconstruction.
AB - OBJECTIVE: This study aims to analyze the relationship between the central
incisor crown inclination and occlusal relationship via three-dimensional study.
METHODS: Ten Chinese volunteers with normal occlusion were selected from physical
examination of college students. Lateral cephalograms and CT scans were taken,
and the CT data were imported into Simplant pro 11.04 to reconstruct three
dimensional model. In the three-dimensional model, every tooth was separated
independently. The upper and lower central incisors were moved labial
inclination(up) or lingual inclination(down) and then the upper and lower tooth
were aligned based on the central incisor's position according to the principles
of Andrew's six keys. Four groups were set up with different changes of central
incisors. The upper and the lower arch were aligned again based on the moved
central incisors. After every motion, the mesio-distal distances of upper and
lower canines and first molars were recorded. All data were analyzed using t-test
via SPSS19.0, and the significance level was set at 5%. RESULTS: The results
showed that the mesio-distal distances of occlusal relationship were different
from normal occlusal relations, when either upper incisor crown inclination or
lower incisor crown inclination was changed, and both upper and lower incisor
crown inclination were moved in same or opposite direction. According to the
statistical analysis, there was no significant difference when the changes of U1
L1 were no more than 10 degrees (P > 0.05). But there was statistically
significant difference (P < 0.05) when changes of U1-L1 were more than 20 degrees
. CONCLUSIONS: The incisor crown inclination has influence on the establishment
of occlusal relationships. The bigger difference upper and lower incisor crown
inclination has, the more deviations from the normal occlusal relationship exist.
PMID- 29957457
TI - Pandemic influenza vaccines: what they have taught us about B cell immunology.
AB - The emergence of avian influenza viruses stimulated pandemic concerns and efforts
to develop protective vaccines. Studies of the immune responses to experimental
vaccines for pandemic influenza have taught us lessons about human immunity to
influenza in general that can be applied to seasonal, pandemic, and even
universal vaccine responses. For example, the concepts of targeting the
hemagglutinin stalk and elicitation of stalk reactive antibodies grew out of
studies of the 2009 pandemic H1N1 vaccines. More recently, the phenomenon of
imprinting, the influence of early life exposure to influenza modifying responses
to the viruses or vaccines later in life, has been reinforced through the study
of potential pandemic influenza virus vaccines such as H7N9. These studies have
also revealed potential strategies to improve responses to novel influenza
strains and produce more broadly cross-reactive B cell and antibody responses.
These concepts are discussed in detail in this review.
PMID- 29957458
TI - Plasma calprotectin and risk of cardiovascular disease: Findings from the PREVEND
prospective cohort study.
AB - BACKGROUND AND AIMS: We aimed to assess the association of circulating
calprotectin, an inflammation-associated protein, with cardiovascular disease
(CVD) risk and determine whether it improves risk prediction. METHODS: Plasma
calprotectin measurements were made at baseline in 5290 participants in the
PREVEND prospective study. Hazard ratios (95% confidence intervals [CI]) for CVD
were calculated. RESULTS: After a median follow-up of 8.3 years, 339 first CVD
events were recorded. Calprotectin concentration was correlated with several
conventional risk factors as well as with high-sensitivity C-reactive protein
(hsCRP) (r = 0.42). Calprotectin was log-linearly associated with CVD risk. The
risk for CVD adjusted for conventional cardiovascular risk factors was 1.26 (95%
CI, 1.13-1.41) per 1 standard deviation higher baseline loge calprotectin, and
was 1.24 (95% CI, 1.11-1.39) following further adjustment for triglycerides, body
mass index, and other potential confounders. The association remained present
after further adjustment for hsCRP 1.15 (95% CI, 1.02-1.30). Comparing extreme
quartiles of plasma calprotectin levels, the corresponding adjusted HRs for CVD
were 1.96 (1.37-2.82), 1.89 (1.31-2.72), and 1.56 (1.07-2.29). The association of
calprotectin with CVD risk did not vary importantly in several relevant clinical
subgroups. Adding calprotectin to the Framingham CVD Risk Score was associated
with a C-index change (0.0016; p=0.42) difference in -2 log likelihood (p=0.038),
IDI (0.0080; p < 0.001), and NRI (4.03%; p=0.024). CONCLUSIONS: There is a log
linear association of calprotectin concentration with risk of CVD, which may be
partly dependent on hsCRP. Adding calprotectin to conventional risk factors
improves CVD risk assessment using measures of reclassification and -2 log
likelihood.
PMID- 29957459
TI - Peak lung function during young adulthood and future long-term blood pressure
variability: The Coronary Artery Risk Development in Young Adults (CARDIA) study.
AB - BACKGROUND AND AIMS: Long-term blood pressure variability (BPV) is associated
with cardiovascular events independent of mean blood pressure (BP); however,
little is known about its predictors. METHODS: Using data from the CARDIA study,
we investigated the association between peak lung-function and long-term BPV in
2917 individuals (mean age 24.8 years, 45.3% males, 58.6% whites) who were not
taking antihypertensive medications. Lung-function was measured using forced
vital capacity (FVC) and forced expiratory volume in 1-s (FEV1) at years 0, 2, 5,
10 and 20 and the maximum score attained was considered as peak lung-function.
Variability independent of the mean (VIM) and coefficient of variation (CV) of BP
were calculated to quantify BPV since achieving peak lung-function across 9
visits over 30 years. RESULTS: In a multivariate linear regression models,
individuals in the 2nd (-0.64 mmHg; 95% CI: -1.06, -0.19), 3rd (-0.96; -1.47,
0.45), and 4th (-0.85: -1.53, -0.17) quartiles of FVC had lower VIM of systolic
BP than the those in quartile 1 (p-trend = 0.005). CV of systolic BP was also
lower by -0.58 (-0.98, -0.19), -0.92 (-1.42, -0.43), and -0.74 (-1.40, -0.08)
percentage points, in the three progressively higher quartiles of FVC compared to
quartile 1 (p-trend = 0.008). Similar findings were observed when the outcome was
diastolic BPV. There was no association of FEV1 and FEV1-to-FVC ratio with BPV.
CONCLUSIONS: These findings suggest that smaller lung volume or restrictive lung
disease during young adulthood, which result in lower peak FVC, may independently
increase the risk of higher long-term BPV during middle adulthood.
PMID- 29957460
TI - Sirtuin 6 inhibits colon cancer progression by modulating PTEN/AKT signaling.
AB - Decreased expression of the tumor suppressor sirtuin 6 (SIRT6) protein plays a
role in tumorigenesis. The aim of this study was to investigate the effects of
SIRT6 and its underlying mechanism in colon cancer progression. As shown by
immunohistochemistry, Western blotting, and the real-time polymerase chain
reaction (RT-PCR), SIRT6 expression was down-regulated in colon cancer tissues
and different colon cancer cell lines, and down-regulation of SIRT6 showed a
negative correlation with the overall survival of colon cancer patients. To
assess the effects of SIRT6 on cell proliferation, apoptosis, invasion, and
migration, 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow
cytometry, transwell, and wound healing assays were carried out, respectively.
Results demonstrated that over-expression of SIRT6 inhibited cell proliferation,
invasion, and migration and enhanced cell apoptosis. Co-immunoprecipitation (Co
IP) and Western blotting showed that up-regulation of SIRT6 increased the
combined quantity of PTEN with SIRT6 proteins, and promoted the expression of
PTEN and PIP2, as well as the stability of PTEN. SIRT6 also reduced the
ubiquitination of PTEN and decreased protein levels of AKT1, phosphatidylinositol
(3,4,5)-trisphosphate (PIP3), mTOR, cyclin d1, and c-myc. In addition, compared
with cells over-expressed SIRT6, cell apoptosis was repressed and cell
proliferation and tumorigenesis were enhanced in cells with SIRT6 over-expression
and PTEN knockdown. In conclusion, the present study confirms that SIRT6
functions as a tumor suppressor gene in colon cancer by modulating PTEN/AKT
signaling, which may provide a novel target for the treatment of colon cancer.
PMID- 29957461
TI - Matrine inhibits hypoxia/reoxygenation-induced apoptosis of cardiac microvascular
endothelial cells in rats via the JAK2/STAT3 signaling pathway.
AB - Hypoxia/reoxygenation (H/R) often results in cellular oxidative stress and the
subsequent apoptosis of cardiac microvascular endothelial cells (CMECs). More
recently, studies have highlighted the therapeutic effects of matrine on various
cardiovascular diseases. Thus, the aim of the present study was to investigate
the underlying mechanism and effects of matrine on hypoxia/reoxygenation (H/R)
induced apoptosis of CMECs in rats. CMECs from Sprague Dawley (SD) rats were
primarily treated with H/R, ld (low-dose, 0.5 mg/mL)-Ma + H/R, md (middle-dose, 1
mg/mL)-Ma + H/R, hd (high-dose, 2 mg/mL)-Ma + H/R, Ma + AG490 + H/R (2 mg/mL
matrine and 50 MUmol/L AG490, a JAK2/STAT3 signaling pathway inhibitor), and
AG490 + H/R in an attempt to identify the underlying regulatory mechanisms of
matrine. MTT assay was applied to determine cell viability. Hoechst staining was
performed to detect the morphology of apoptotic CMECs, while cell cycle and the
rate of apoptosis rate were determined by flow cytometry means. The mRNA and
protein expression of the JAK2/STAT3 signaling pathway and apoptosis related
genes were determined through the use of RT-qPCR and western blot assay methods
respectively. An in vitro angiogenesis assay was employed to evaluate the value
of matrine in tube formation. CMECs treated with ld-Ma+H/R, md-Ma+H/R, hd-Ma+H/R
and Ma + AG490+H/R exhibited higher cell viability, greater cell ratio at the S
phase, higher expression levels of p-JAK2 and p-STAT3, increased tube formation
ability, and a lower apoptosis rate, with a lower ratio of cells at the G1 phase
and Bax/Bcl-2 ratio. Meanwhile, the rats treated with AG490+H/R exhibited
opposite results. Taken together, the key findings of the present study suggest
that matrine inhibits the H/R-induced apoptosis of CMECs in rats via the
JAK2/STAT3 signaling pathway, highlighting its therapeutic potential for H/R
injury.
PMID- 29957462
TI - Magnesium isoglycyrrhizinate ameliorates liver fibrosis and hepatic stellate cell
activation by regulating ferroptosis signaling pathway.
AB - Ferroptosis is recently reported as a new mode of regulated cell death. It is
triggered by disturbed redox homeostasis, overloaded iron and increased lipid
peroxidation. Howerver, the role of ferroptosis in hepatic fibrosis remains
obscure. In the current study, we attempted to investigate the effect of
Magnesium isoglycyrrhizinate (MgIG) on ferroptosis in liver fibrosis, and to
further clarify the possible mechanisms. Our data showed that MgIG treatment
markedly attenuated liver injury and reduced fibrotic scar formation in the rat
model of liver fibrosis. Moreover, experiments in vitro also confirmed that MgIG
treatment significantly decreased expression of hepatic stellate cell (HSC)
activation markers. Interestingly, HSCs treated by MgIG presented morphological
features of ferroptosis. Furthermore, MgIG treatment remarkably induced HSC
ferroptosis by promoting the accumulation of iron and lipid peroxides, whereas
inhibition of ferroptosis by specific inhibitor ferrostatin-1 (Fer-1) completely
abolished MgIG-induced anti-fibrosis effect. More importantly, our results
determined that heme oxygenase-1 (HO-1) was in the upstream position of MgIG
induced HSC ferroptosis. Conversely, HO-1 knockdown by siRNA evidently blocked
MgIG-induced HSC ferroptosis and in turn exacerbated liver fibrosis. Overall, our
research revealed that HO-1 mediated HSC ferroptosis was necessary for MgIG to
ameliorate CCl4-induced hepatic fibrosis.
PMID- 29957463
TI - Long non-coding RNA FEZF1-AS1 promotes cell invasion and epithelial-mesenchymal
transition through JAK2/STAT3 signaling pathway in human hepatocellular
carcinoma.
AB - Long non-coding RNAs (lncRNAs) have emerged as key regulators in the development
of hepatocellular carcinoma (HCC). In the present study, we explored the
expression profile and biological role of lncRNA FEZF1-AS1 in HCC. We observed
remarkable upregulation of FEZF1-AS1 in HCC tissues and cell lines, and high
FEZF1-AS1 expression was correlated with aggressive phenotypes and poor prognosis
of HCC patients. Furthermore, we found that FEZF1-AS1 knockdown markedly
inhibited the proliferation of HCC cells by inducing cell cycle arrest. In
addition, FEZF1-AS1 knockdown suppressed HCC tumor growth in vivo. Moreover,
FEZF1-AS1 knockdown inhibited the migration and invasion of HCC cells through
suppression of JAK2/STAT3 signaling-mediated epithelial-mesenchymal transition
(EMT). In conclusion, the present study for the first time demonstrated that
FEZF1-AS1 serves as an oncogenic lncRNA in human HCC and implicated FEZF1-AS1 as
a valuable therapeutic target for HCC treatment.
PMID- 29957464
TI - The unique DEK oncoprotein in women's health: A potential novel biomarker.
AB - Breast and cervical cancer are the first and fourth cancer types with the highest
prevalence in women, respectively. The developmental profiles of cancer in women
can vary by genetic markers and cellular events. In turn, age and lifestyle
influence in the cellular response and also on the cancer progression and
relapse. The human DEK protein, a histone chaperone, belongs to a specific
subclass of chromatin topology modulators, being involved in the regulation of
DNA-dependent processes. These epigenetic mechanisms have dynamic and reversible
nature, have been proposed as targets for different treatment approaches,
especially in tumor therapy. The expression patterns of DEK vary between healthy
and cancer cells. High expression of DEK is associated with poor prognosis in
many cancer types, suggesting that DEK takes part in oncogenic activities via
different molecular pathways, including inhibition of senescence and apoptosis.
The focus of this review was to highlight the role of the DEK protein in these
two female cancers.
PMID- 29957465
TI - 1,25(OH)2D3 promotes chondrocyte apoptosis and restores physical function in
rheumatoid arthritis through the NF-kappaB signal pathway.
AB - We explored the modulatory effect of 1,25(OH)2D3 on chondrocytes and physical
function in rats with RA and its mechanism underlying the regulation of NF-kappaB
signal pathway. RA patients and healthy volunteers were selected. Sprague-Dawley
(SD) rats were used to establish RA models. The paw volume of rats was estimated.
Chondrocytes were isolated from RA rats. The protein levels in both cartilage
tissues and chondrocytes were determined using western blotting. Apoptosis was
evaluated using TUNEL assay. Serum levels of IL-1beta, IL-6, IL-10 and IL-17 were
measured by enzyme-linked immunosorbent assay (ELISA). Serum levels of
1,25(OH)2D3 were lower in RA patients than in healthy volunteers. Rats in the RA
+ VD3 group were lighter than those in normal and PBS groups, with an increased
paw volume, severer joint swelling, higher expression levels of p-IkappaBalpha, p
p65, IL-1beta, IL-6, and IL-17, and lower expression level of IL-10, while those
in RA and RA + VD3 + NF-kappaB group differed more significantly. In addition, by
comparing RA rats and RA + NF-kappaB rats, we found that TNF-alpha stimulation
exacerbated RA, increased expression levels of p-IkappaBalpha, p-p65, IL-1beta,
IL-6, and IL-17, and decreased the expression level of IL-10. Compared with RA
chondrocytes, chondrocytes from RA + VD3 rats exhibited lower expression levels
of p-IkappaBalpha and p-p65, and had more apoptotic cells, while those from RA +
NF-kappaB rats showed an opposite trend. Taken together, 1,25(OH)2D3 accelerates
chondrocyte apoptosis and improve physical function in rats with RA by the
inhibition of NF-kappaB signal pathway.
PMID- 29957466
TI - The intervention effect of zuogui pill on chronic kidney disease-mineral and bone
disorder regulatory factor.
AB - Chronic kidney disease-mineral and bone disorder (CKD-MBD) play a critical role
in the pathogenesis of cardiovascular complications in patients with chronic
kidney disease (CKD). Zuogui pill as a traditional Chinese herbal drug has been
used for nourish kidney essence improve bone malnutrition of renal bone disease
by regulating the metabolism of calcium and phosphorus and participating in
osteoblast metabolism. In the present study, 5/6 nephrectomy rat model was used
to reveal the mechanism of zuogui pill in treatment of CKD-MBD. Compared with
sham rats, the levels of serum phosphorus, PTH, iPTH and creatinine were
significantly decreased, while the serum calcium level was significantly
increased, and the Cbfa1 protein level was significantly decreased and FGF23
protein level was significantly increased by Zuogui pill treatment. Compared with
model rats, the BMD of rat was significantly increased by Zuogui pill treatment.
Histological analysis revealed that the kidney injury of rats with CKD was
significantly reduced by zuogui pill treatment. Compared with model rats, the
CYP27B1 mRNA level was significantly increased, and the PTH mRNA level and
NaPiIIa protein level were significantly decreased in the kidney by zuogui pill
treatment. We inferred that zuogui pill exhibited potential therapeutic effects
on CKD-MBD in the rats by regulating bone metabolism and nourish kidney.
PMID- 29957467
TI - Long non-coding RNA PVT1 promotes cell proliferation and invasion through
regulating miR-133a in ovarian cancer.
AB - The long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), was
reportedly to be highly expressed in a variety of tumors including ovarian cancer
(OC). However, the role and mechanism of action of PVT1 in the carcinogenesis and
progression of OC remains largely unknown. PVT1 and miR-133a expression were
detected by quantitative real time PCR(qRT-PCR) assays in OC tissues and cell
lines. Cell Counting Kit-8 (CCK-8), flow cytometer, wound healing and transwell
invasion assays were performed to evaluate cell proliferation, cycle, migration
and invasion abilities, respectively. qRT-PCR and luciferase reporter assays
demonstrated PVT1 regulated miR-133a expression. Here, we discovered that PVT1
shows higher expression in OC tissues than in normal ovarian tissues, and
patients who show higher expression of PVT1 have worse progression-free and
overall survivals compared to lower expression of PVT1. Additionally, we observed
that knockdown of PVT1 significantly inhibited OC cell proliferation, and
decreased the migration and invasion capabilities of OC cells. Mechanistically,
miR-133a was identified to serve as a direct downstream target of PVT1 in OC.
Knockdown of PVT1 inhibited cell proliferation, migration and invasion through
negative regulating miR-133a in OC cells. Taken together, our finding shows that
PVT1 may be a novel biomarker for prognosis and a promising therapeutic target
for OC.
PMID- 29957468
TI - Fatty acid binding protein 5 promotes tumor angiogenesis and activates the
IL6/STAT3/VEGFA pathway in hepatocellular carcinoma.
AB - BACKGROUND: Tumor angiogenesis is an essential process for facilitating tumor
growth and metastasis. Fatty acid binding protein 5(FABP5)is highly expressed in
hepatocellular carcinoma (HCC). Thus, we investigated the role of FABP5 in tumor
angiogenesis during HCC development. METHODS: In this study, the protein and mRNA
levels of FABP5 in matched HCC and adjacent noncancerous liver tissues from 43
patients were determined using immunohistochemistry and real-time quantitative
PCR, respectively. Two HCC cell lines (Huh7 and SMMC-7721) and human umbilical
vein endothelial cells (HUVECS) were used to investigate the pro-angiogenic
effect of FABP5 by tube formation, CCK8 and Transwell migration assays. The
expression levels of interleukin 6 (IL6) and vascular endothelial growth factor A
(VEGFA) secreted from HCC cells were detected by enzyme-linked immunosorbent
assay (ELISA). RESULTS: In 43 HCC patients, the expression of FABP5 mRNA was
positively correlated with intratumoral VEGFA mRNA expression. FABP5 mRNA
expression was also associated with adverse HCC characteristics. In vitro, cell
viability, cell migration and tube formation in HUVECs were enhanced with
increasing expression of FABP5 in HCC cells. Downregulation of FABP5 expression
inhibited the IL6/STAT3/VEGFA pathway in HCC cells and inhibited tumor
angiogenesis. CONCLUSION: FABP5 was shown to promote angiogenesis and activate
the IL6/STAT3/VEGFA pathway in HCC. FABP5 may be a potential antiangiogenic
target in the treatment of HCC.
PMID- 29957469
TI - Valproic acid attenuates Abeta25-35-induced neurotoxicity in PC12 cells through
suppression of mitochondria-mediated apoptotic pathway.
AB - Aggregation of amyloid-beta (Abeta) peptides is a pathological hallmark of
Alzheimer's disease (AD). The purpose of the present study was to identify the
protective role of valproic acid (VPA) against beta-amyloid protein fragment 25
35 (Abeta25-35)-caused neurotoxicity in PC12 cells. Different doses of VPA was
added to cultures of differentiated PC12 cells, 1 h before Abeta25-35. We found
that VPA effectively prevented Abeta25-35-stimulated cytotoxicity through
attenuating apoptosis and increasing the ratio of Bcl-2/Bax in PC12 cells. VPA
also significantly inhibited the generation of ROS induced by Abeta25-35 in PC12
cells in a dose-dependent manner. In addition, VPA significantly alleviated
mitochondrial dysfunction through improvement of mitochondrial membrane
potential, inhibition of cytochrome c release, and promotion of mitochondrial ATP
synthesis. Furthermore, VPA treatment reduced the expression levels of
proinflammatory cytokines and attenuated the activation of NF-kappaB signaling.
In conclusion, our results suggested that VPA might serve as a novel protective
agent against Abeta25-35-induced cytotoxicity in AD.
PMID- 29957470
TI - The inhibition of Hippo/Yap signaling pathway is required for magnesium
isoglycyrrhizinate to ameliorate hepatic stellate cell inflammation and
activation.
AB - Liver fibrosis is a reversible pathological process accompanied by abnormal
inflammation, and its end-stage cirrhosis is responsible for high morbidity and
mortality worldwide. This study was to investigate the effect of Magnesium
isoglycyrrhizinate (MgIG) on liver fibrosis and inflammation, and to further
clarify molecular mechanism. We found that MgIG treatment significantly
alleviated carbon tetrachloride (CCl4)-induced liver fibrosis and HSC activation
by regulating TGF-beta signaling and MMP/TIMP systems. In addition, MgIG
treatment significantly inhibited the inflammatory response of liver fibrosis in
mice characterized by reduced pro-inflammatory factors expression and increased
anti-inflammatory factors expression. Interestingly, experiments in vitro also
showed that MgIG treatment significantly reduced the expression of hepatic
stellate cell (HSC) activation markers. Besides, MgIG treatment not only
inhibited the expression of pro-inflammatory factors, but also promoted the
production of anti-inflammatory factors in activated HSCs. Importantly, treatment
with MgIG inhibited Hippo/Yap signaling pathway, which was a potential mechanism
for MgIG-induced anti-inflammatory effects. The overexpression of Hippo/Yap
signaling effector YAP completely impaired MgIG-induced anti-inflammatory and
anti-fibrotic effects. Taken together, these results provide novel implications
to reveal the molecular mechanism of the anti-inflammatory properties induced by
MgIG, by which points to the possibility of using MgIG to treat liver fibrosis.
PMID- 29957471
TI - Neuroprotective effect of 1-Deoxynojirimycin on cognitive impairment, beta
amyloid deposition, and neuroinflammation in the SAMP8 mice.
AB - beta-amyloid deposition and neuroinflammation play a crucial part in Alzheimer's
disease. Therefore, this study was designed to find the effects of 1
deoxynojirimycin (DNJ) purified from mulberry leaves on pathological deposition
of Abeta peptides and neuroinflammation in senescence-accelerated-prone mouse 8
(SAMP8) mice. Compared to senescence-accelerated-resistant mouse 1 (SAMR1) mice,
SAMP8 mice exhibited conspicuous declines in spatial memory abilities and brain
derived neurotrophic factor (BDNF) and tyrosine kinase receptors (TrkB) level in
hippocampus; increased Abeta deposition, beta-secretase (BACE1) level, microglia
activation and inflammatory factors, including interleukin-1beta (IL-1beta),
interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in the brain.
The SAMP8 mice were treated with DNJ (40 or 160 mg/kg/day) by oral administration
for two months. Our results indicated that DNJ treatment improved these changes,
and the 160-mg/kg/day DNJ group revealed more significant alleviation. Therefore,
DNJ potentially has the neuroprotective effect by inhibiting BACE1 expression,
attenuating Abeta deposition, remitting neuroinflammation, and up-regulating the
BDNF/TrkB signal pathway in the brain.
PMID- 29957472
TI - Antioxidant and anti-inflammatory properties of marmelosin from Bael (Aegle
marmelos L.); Inhibition of TNF-alpha mediated inflammatory/tumor markers.
AB - Oxidative stress and inflammation are important critical factors that are
implicated in almost all life style disorders such as diabetes, cardiovascular
disease, ulcer and cancer. Current study aimed at isolation and characterization
of a furanocoumarin from Bael (Aegle marmelos L.) fruit that can modulate both
oxidative stress and inflammation effectively. Ethyl acetate extract of Bael
fruit (EAFB) was subjected to HPLC for identification, purified and characterized
using FTIR, NMR and ESI-MS analysis. Predominant peak of EAFB at RT 12.54 min on
HPLC was identified as marmelosin with molecular weight of m/z ~ 271.2.
Marmelosin was evaluated for antioxidant, antiproliferative, apoptotic, cancer
(Tyrosinase & Galectin-3) and immunomodulatory (NO, TNF-alpha) potentials
employing standard assay systems. Marmelosin possessed potent antioxidant
activity with IC50 of ~ 15.4 +/- 0.32 MUM as opposed to standard - gallic acid
(IC50 1.1 +/- 0.08 MUM), antiproliferative activity with IC50 of ~ 6.24 +/- 0.16
MUM as opposed to deferoxamine (~10.8 +/- 0.28 MUM) and protected cells against
cellular/DNA damage. Anti-inflammatory property was evident with significant
reduction in the release of NO (~3.9 fold) and TNF-alpha (~3.4 fold), a pro
inflammatory cytokine, in addition to the inhibition of NFkappaB (~2.7 fold), a
transcription factor in Raw 264.7 cells. Marked down regulation of galectin-3
(~5.5 folds) and tyrosinase (~11.1 folds) by gene expression analysis
substantiated by tyrosinase inhibition (IC50 - 20.3 +/- 1.26 MUM Vs. Kojic acid -
IC50 - 24.1 +/- 1.41 MUM) and molecular docking studies strengthened the cancer
modulatory property of marmelosin. In addition, marmelosin induced apoptotic
bodies, chromatin condensation and nulcear blebbing in Raw 264.7 cells commending
the apoptotic effect of marmelosin. Marmelosin thus displayed potential multi
potent antioxidant, anti-inflammatory and anticancer properties via TNF-alpha
mediated Akt signaling pathway.
PMID- 29957473
TI - Choice in the presence of experts: The role of general practitioners in patients'
hospital choice.
AB - This paper considers the micro-econometric analysis of patients' hospital choice
for elective medical procedures when their choice set is pre-selected by a
general practitioner (GP). GPs have a dual role with regard to elective referrals
in the English NHS, advising patients and at the same time taking account of the
financial implications of referral decisions on local health budgets. The paper
proposes a two-stage choice model that encompasses both patient and GP level
optimization. It demonstrates that estimators that do not take account of
strategic pre-selection of choice sets may be biased and inconsistent. We find
that GPs as patients' agents select choice options based on quality, but as
agents of health authorities also consider financial implications of referrals.
When considering these choice options, patients focus on tangible hospital
attributes, like amenities.
PMID- 29957474
TI - Sub therapeutic rivaroxaban plasma concentrations following administration via
Percutaneous Endoscopic Gastrostomy (PEG) feeding tubes - A note of caution.
PMID- 29957475
TI - Fibrinolytic potential of DS-1040, a novel orally available inhibitor of
activated thrombin-activatable fibrinolysis inhibitor (TAFIa).
AB - An activated thrombin-activatable fibrinolysis inhibitor (TAFIa) attenuates
fibrinolysis by removing C-terminal lysine/arginine residues from partially
degraded fibrin. We have identified a novel low-molecular-weight inhibitor of
TAFIa, DS-1040, to be potentially useful for treating thrombotic diseases. In
this study, we investigated its in vitro pharmacological profile and in vivo
effects in animal models of microthrombosis and bleeding. DS-1040 inhibited human
TAFIa and carboxypeptidase N (CPN) in vitro with IC50 values of 5.92 and 3.02 *
106 nmol/L, respectively, suggesting that DS-1040 is highly selective for TAFIa
over CPN. DS-1040 did not affect platelet aggregation and coagulation time. In a
tissue factor-induced rat microthrombosis model, intravenously administered DS
1040 reduced existing fibrin clots in the lung, whereas post-treatment with
enoxaparin had limited effect. Both intravenously and orally administered DS-1040
elevated plasma D-dimer levels with similar plasma exposures of DS-1040. DS-1040
significantly augmented plasma D-dimer level on top of silent dose of recombinant
tissue-plasminogen activator (t-PA), suggesting DS-1040 enhances fibrinolytic
activity of t-PA. In addition, DS-1040 did not prolong the tail bleeding time
beyond its efficacy dose. These results indicate that DS-1040 is a potent,
selective, intravenously/orally available inhibitor of TAFIa with minimum risk of
bleeding. DS-1040 is a potential novel fibrinolysis enhancer useful in treating
thrombotic diseases.
PMID- 29957476
TI - Aripiprazole and pregnancy: A retrospective, multicentre study.
AB - BACKGROUND: Aripiprazole is a second generation antipsychotic medication that has
been a useful addition to the treatment of severe mental illness due to its low
metabolic and sedation risk profile. Pregnancy is a time of high risk of
metabolic complications such as gestational diabetes and the postpartum period is
often a time when sedation can compromise infant care. To date there is limited
data in pregnancy on the safety of aripiprazole use. While available data do not
suggest an elevated malformation risk in pregnancy, there is less information
available on pregnancy and neonatal complications. METHODS: This study presents
preliminary data on pregnancy and neonatal complications on 26 women who took
aripiprazole in pregnancy. These women attended at antenatal clinics for women
with severe mental illness at two hospitals in Australia. RESULTS: Overall
aripiprazole was not associated with an increased risk of gestational diabetes.
However, use of aripiprazole in pregnancy was associated with an increased risk
of pregnancy hypertension, lower birth weight, shorter gestation at birth and
higher rates of admission of the neonate than the expected population rates.
LIMITATIONS: These findings need to be replicated in a larger, well-designed
study to ensure they do not reflect confounding factors. CONCLUSIONS: Findings
demonstrate that aripiprazole is unlikely to pose a metabolic risk in pregnancy
but other pregnancy complications including hypertension, need to be examined in
further studies.
PMID- 29957477
TI - 5-HTT mRNA level as a potential biomarker of treatment response in patients with
major depression in a clinical trial.
AB - OBJECTIVES: To investigate whether the serotonin transporter (5-HTT or SERT or
SLC6A4) mRNA level could be used as a biomarker of treatment response in patients
with major depression treated with different antidepressants while controlling
related factors. METHODS: One hundred and nineteen patients with major depression
were recruited; all genotyped for the 5-HTT polymorphism concerning 5-HTTLPR,
rs25531, and STin2 VNTR, provided demographic data and completed relevant
questionnaires. Duloxetine and paroxetine were administered over 32 weeks to
these patients. The Hamilton depression rating scale (HDRS) and 5-HTT mRNA level
were evaluated at baseline (Week 0), and at 8, 16, 24 and 32 weeks. RESULTS:
Improvement in depressive symptoms (HDRS score declined) and increasing in 5-HTT
mRNA level were found with longer duration of antidepressant treatment in
patients with major depression. Patients with more 5-HTTPR long-form alleles and
STin2.12 alleles had poor antidepressant treatment response. Duloxetine may give
a better treatment response than paroxetine. Using structural equation modeling
(SEM), the 5-HTTLPR long-form had a direct positive association with the 5-HTT
mRNA level and an indirect adverse relationship with the 5-HTT mRNA level through
neuroticism and previous suicide attempts. CONCLUSION: The 5-HTT mRNA level
increased and correlated with the treatment response (HDRS score improvement)
under 32-weeks antidepressants treatment clinical trial. We speculate that the 5
HTT mRNA level may be used as a potential biomarker of antidepressant treatment
response.
PMID- 29957478
TI - CSF miR-16 expression and its association with miR-16 and serotonin transporter
in the raphe of a rat model of depression.
AB - BACKGROUND: Depression is a common mental disorder with unknown mechanism.
Emerging evidence shows that miRNAs play a critical role in the process of
depression. Here we reported the cerebrospinal fluid (CSF) miR-16 expression and
its association with miR-16 and serotonin transporter (SERT) in the raphe of a
rat model of depression. METHODS: 20 rats were randomized to the control or CUMS
(chronic unpredictable mild stress) group. The rats in the CUMS group underwent
CUMS for 21 days, while those in the control group received no treatment. After
anesthetization, CSF was collected for the measurement of miR-16. Then raphes
from all rats were separated for determination of miR-16 and SERT protein.
RESULTS: The expression levels of miR-16 in CSF and raphe of the CUMS group were
significantly lower than those of the control group (P = 0.007 and 0.031).
However, SERT protein in raphe of the CUMS group was obviously increased as
compared that of the control group (P = 0.005). There was a positive correlation
between CSF miR-16 and raphe miR-16 (r = 0.95, P = 0.000). Meanwhile, negative
correlations between miR-16 and SERT protein in raphe (r = -0.70 P = 0.02),
between CSF miR-16 and raphe SERT protein (r = -0.86, P = 0.002) were observed in
the CUMS group. LIMITATIONS: We have not explored the reason why CSF miR-16 was
decreased in the rat model of depression and only tested the association of miR
16 between CSF and raphe. CONCLUSIONS: CSF miR-16 was involved in the
pathogenesis of depression via reflecting raphe miR-16 level, and thus affecting
raphe SERT expression.
PMID- 29957479
TI - Body mass index and risk of suicide: A systematic review and meta-analysis.
AB - BACKGROUND: Studies have examined associations between obesity and suicide.
However, the overall outcomes of the studies are not fully elucidated, and the
orientation of these studies needs to be identified. The aim of this systematic
review and meta-analysis was to determine the suicide risk based on body mass
index (BMI). METHODS: The authors systematically searched PubMed, Scopus,
PsycInfo and Google Scholar databases until December 2017. After the screening
process, 15 prospective studies were included in meta-analysis. Stata-14 was used
for meta-analysis. Forest Plot was calculated for the whole of the 15 studies and
the subgroups; publication bias was examined as well. RESULTS: In obesity group,
Pooled Risk Ratio (RR) was achieved for suicide mortality (RR = 0.67; 95%
confidence interval (CI) CI = 0.54-0.81) and suicidal ideation (RR = 1.50; 95% CI
= 0.76-2.23). It was also measured in overweight group, for suicide mortality (RR
= 0.78; 95% CI = 0.71-0.85) and suicidal ideation (RR = 1.17; 95% CI = 0.65
1.69). CONCLUSION: Overall, there is an inverse association between obesity and
overweight with suicide mortality and attempted suicide, and positive association
between obesity and overweight with suicidal ideation. There was no evidence of
publication bias. Overall, our findings indicate the role of BMI in suicide.
PMID- 29957480
TI - Risk factors of new onset anxiety and anxiety exacerbation in the perinatal
period: A systematic review and meta-analysis.
AB - BACKGROUND: Even though more than 20% of women meet diagnostic criteria for an
anxiety disorder during the perinatal period, very little is known about the
predictors of these problems. As a result, we systematically reviewed the
literature on risk factors for new onset anxiety and maternal anxiety
exacerbation in the perinatal period. METHODS: PubMed, MEDLINE, PsycINFO, CINAHL,
Ovid, ProQuest Portal, and Web of Science were searched for studies assessing
risk factors for the development of new onset anxiety or anxiety worsening in
women during pregnancy and the postpartum period. RESULTS: 11,759 citations were
identified, with 11 studies meeting eligibility criteria. New onset anxiety was
assessed in 7 studies, anxiety worsening in 3, and 1 assessed both. Lower
educational attainment, living with extended family members, multiparity, a
family history of psychiatric disorders, hyperemesis gravidarum, comorbid sleep
disorders, and prenatal oxytocin exposure were risk factors for new onset
perinatal anxiety, while presence of comorbid psychiatric disorders and prenatal
oxytocin were risk factors for anxiety worsening. LIMITATIONS: Studies not
explicitly stating whether participants had pre-existing anxiety disorders were
excluded. As a result, meta-analysis was not possible for several risk factors.
CONCLUSIONS: Risk factors for new onset anxiety and anxiety worsening during the
perinatal period include psychological, social, and biological exposures. Given
the lack of studies differentiating women with and without pre-existing anxiety
disorders, additional research is required in order to determine whether these
factors differ from the non-puerperal population, as well as from each other.
PMID- 29957481
TI - What is the nonverbal communication of depression? Assessing expressive
differences between depressive patients and healthy volunteers during clinical
interviews.
AB - BACKGROUND: It is unclear if individuals with Major Depressive Disorder (MDD)
present different nonverbal behavior (NVB) compared with healthy individuals, and
also if depression treatments affect NVB. In this study, we compared the NVB of
MDD subjects and healthy controls. We also verified how MDD subjects' NVB is
affected by depression severity and acute treatments. METHODS: We evaluated 100
MDD outpatients and 83 controls. We used a 21-category ethogram to assess the
frequency of positive and negative NVB at baseline. MDD subjects were also
assessed after eight weeks of treatment (pharmacotherapy or neuromodulation). We
used the Wilcoxon signed-rank test to compare the NVB of MDD subjects and
controls; beta regression models to verify associations between MDD severity and
NVB; the Shapiro-Wilk test to verify changes in NVB after treatment; and logistic
regression models to verify NVB associated with treatment response according to
the Hamilton depression rating scale. RESULTS: Compared with controls, MDD
subjects presented higher levels of six negative NVB (shrug, head and lips down,
adaptive hand gestures, frown and cry) and lower levels of two positive NVB (eye
contact and smile). MDD subjects' NVB was not associated with depression
severity, and did not significantly change after depression treatment. Treatment
responders showed more interpersonal proximity at baseline than non-responders.
LIMITATIONS: Our ethogram had no measure of behavior duration, and we had a short
follow-up period. CONCLUSIONS: MDD subjects have more negative and less positive
social NVB than controls. Their nonverbal behavior remained stable after clinical
response to acute depression treatments.
PMID- 29957482
TI - The development and psychometric properties of the bipolar disorders knowledge
scale.
AB - PURPOSE: Bipolar Disorder (BD) presents in 1-4% of the world's population,
carrying significant financial and functional consequences. Beyond the direct
disease burden, patients with BD experience a high degree of both internal and
external stigma. Additionally, medication adherence tends to be poor in patients
with BD. Knowledge appears to play a role in mitigating both stigma and non
adherence, but these relationships have not been fully elucidated. The Bipolar
Disorder Knowledge Scale (BDKS) was designed to explore the role of knowledge and
better define such relationships. This research provides the evidence for the
reliability and validity of the scale. METHODS: Forty-seven items were developed
to assess knowledge of BD. The 47-item survey was sent out to two groups: first a
group of 43 pharmacists with BCPP credentials from the College of Psychiatric and
Neurologic Pharmacists (CPNP) who were recruited from the CPNP directory, and
second a group of 250 members of the general public who were recruited using
Qualtrics Online Sample service. Participants were surveyed on their education
status, health literacy, BD diagnostic status, and exposure to patients with BD.
Participants then completed the 47-item scale. After 48 h 100 members from the
original general public group were sent the same survey to assess test-retest
reliability. For each item a difficulty index to evaluate how well participants
performed on the item and a discrimination index to determine how well each item
performed in high-scorers versus low scorers were calculated. Additionally,
Cronbach's alpha was calculated to determine internal consistency validity and a
Pearson correlation was run to determine test-retest reliability. Items were
removed based on the results from the difficulty index, discrimination index, and
Cronbach's alpha. Finally the pharmacist final scores were compared to the
general public using an unpaired t-test to assess whether content experts were
more likely to perform better on the scale. Following item removal, the scale was
finalized at 25-items. RESULTS: The mean score for the scale was 34.48 (71.83%;
SD: 5.50) and the Cronbach's alpha was 0.773 before item analysis. Following item
analysis, 22 items were dropped leaving 25 items on the final version of the
scale. The remaining items retained a difficulty index below 90% and a
discrimination index above 20%. The mean of the 25-item scale was 18.40 (73.6%;
SD: 4.13) for the general public and 23.20 (92.8%; SD: 1.36) for the pharmacists
group (p < 0.001). The Cronbach's alpha for the finalized scale was 0.760,
indicating a high-degree of internal consistency. While this is lower than the
original alpha, this may be explained by the reduced number of scale items. A 25
item scale is much more practical and the items on the scale retain stronger item
analysis statistics. Finally, the Pearson Correlation for the group who underwent
the test-retest procedure was 0.841 (p < 0.001) indicating strong test-retest
reliability. CONCLUSION: The BDKS is a 25-item true-false scale that takes
approximately 5-10 min to complete. The scale assesses knowledge of BD with items
targeting diagnosis, etiology, disease course, symptoms, treatment, and life
impact. The scale has shown strong internal consistency and test-retest
reliability in a general population and will be useful for evaluating knowledge
of BD as it relates to stigma, non-adherence, and other variables.
PMID- 29957483
TI - Different patterns of alcohol consumption and the incidence and persistence of
depressive and anxiety symptoms among older adults in Ireland: A prospective
community-based study.
AB - BACKGROUND: The associations of different patterns of alcohol consumption and the
incidence and persistence of depressive and anxiety symptoms in older age remain
unclear. METHODS: Data on 6095 adults aged >= 50 years old from the Irish
Longitudinal Study on Aging (TILDA) was analyzed. Participants completed the CAGE
instrument to screen for problematic alcohol use at baseline between October 2009
and February 2011. Outcomes were incident (assessed by the CES-D scale) and
anxiety (assessed by the Hospital Anxiety and Depressive scale) symptoms after a
two-year follow-up as well as persistence of probable depression and anxiety
among those with a positive screen for those disorders at baseline. Associations
were adjusted for potential confounders through multivariable models. RESULTS: In
the overall sample, problem drinking did not predict incident and persistent
depression and anxiety in this sample. Among females, problem drinking increased
the risk for incident depression (OR = 2.11; 95%CI = 1.12-4.00) and anxiety (OR =
2.22; 95%CI = 1.01-4.86). In addition, problem drinking increased the risk of
persistent depressive symptoms (OR = 2.43; 95%CI = 1.05-5.06) among females.
CONCLUSION: Problem drinking may increase the risk of incident probable
depression and anxiety among older females. Furthermore, problem drinking led to
a higher likelihood of persistent depressive symptoms in older female
participants. Interventions targeting problem drinking among older females may
prevent the onset and persistence of depression in this population, while also
decreasing the incidence of anxiety symptoms.
PMID- 29957484
TI - Interplay of disorder and delocalization in photosynthetic light harvesting.
AB - Photosystems, the machines of photosynthesis, are highly complex and
energetically disordered pigment-protein structures. Yet, they perform their
function, be it highly efficient energy transfer and charge separation or the
ability to switch between light-harvesting and photoprotective states, extremely
well. In this opinioned review we describe the interplay of disorder and exciton
delocalization in photosynthetic light harvesting. By discussing recent research
advances on grounds of well-established concepts, we demonstrate that not only is
the excitation delocalization a robust phenomenon, but that it in fact enables
the light-harvesting function in the disordered environment.
PMID- 29957485
TI - The paradigm of obstructive sleep apnea in aging: interactions with telomere
length.
PMID- 29957486
TI - Prevalence and characteristics of positional sleep apnea in the HypnoLaus
population-based cohort.
AB - OBJECTIVE/BACKGROUND: To determine the prevalence of positional obstructive sleep
apnea (POSA) and exclusive POSA (ePOSA) in the general population and to assess
the factors independently associated with POSA and ePOSA according to gender and
menopausal status. PATIENTS/METHODS: Participants of the population-based
HypnoLaus Sleep Cohort underwent full polysomnography at home. POSA was defined
as an apnea-hypopnea index (AHI) >=5/h, and supine/non-supine AHI ratio
(sAHI/nsAHI) >=2 (ePOSA when non-supine AHI was normalized). RESULTS: In this
study, 1719 subjects (40-85y.o. 46% men) with at least 30 min spent in both the
supine and non-supine positions were included. OSA was present in 1224 subjects
(71%) (AHI >5/H). POSA was present in 53% of all subjects, and in 75% of OSA
subjects. ePOSA was present in 26% of all subjects and in 36% of OSA subjects. In
multivariate analyses, lower AHI and lower BMI were both associated with POSA and
ePOSA in males. In premenopausal females, no single factor was associated with
POSA while a lower AHI and an Epworth sleepiness scale >10 were associated with
ePOSA. In postmenopausal women, a lower BMI was associated with POSA and a lower
AHI and a lower Mallampati score with ePOSA. CONCLUSIONS: In this large
population-based study, we found that POSA is present in 53% of the middle-to
older age general population, and in 75% of OSA subjects. ePOSA was present in
36% of OSA subjects, suggesting that a large proportion of them could be treated
with positional therapy. AHI and BMI were differently associated with POSA in
men, and pre or post-menopausal women.
PMID- 29957487
TI - Patients with chronic insomnia disorder have increased serum levels of
neurofilaments, neuron-specific enolase and S100B: does organic brain damage
exist?
AB - OBJECTIVES: The aims of this study were to investigate whether serum levels of
neurofilaments heavy chain (NfH) and light chain (NfL), neuron-specific enolase
(NSE) and S100 calcium binding protein B (S100B): (1) change, (2) alleviate in
post-therapy and (3) are associated with sleep quality and cognitive dysfunction,
in patients with chronic insomnia disorder (CID). METHODS: Forty CID outpatients
constituted free-therapy group (ft-CID), in which twenty-four patients completed
follow-up after six-month treatment to form re-visiting group (rv-CID), and
twenty healthy good sleepers constituted control group (HC). All subjects
completed questionnaires, polysomnography, Chinese-Beijing Version of Montreal
Cognitive Assessment (MoCA-C) and Nine Box Maze Test (NBMT) to assess sleep and
neuropsychological function. The serum levels of NfH, NfL, NSE and S100B were
detected using enzyme-linked immunosorbent assay. RESULTS: The ft-CID had higher
levels of NfH, NfL, NSE and S100B than the HC. Of note, the levels of NfH, NfL
and NSE were significantly reduced in the rv-CID compared to the ft-CID, but not
the level of S100B. Principal components analysis revealed that in these serum
biomarkers, NfL and S100B had a substantial correlation with subjective and
objective sleep parameters. CONCLUSIONS: The CID patients had elevated serum
levels of NfH, NfL, NSE and S100B, indicating existence of damaged brain
microstructure, including neurons, astrocytes and neuronal terminals, which were
associated with the insomniac severity or/and cognitive dysfunction and could
significantly reduce after effective therapy apart from the S100B.
PMID- 29957488
TI - APOBEC and ADAR deaminases may cause many single nucleotide polymorphisms curated
in the OMIM database.
AB - Cytosine and adenosine deamination events (DNA, RNA substrates) account for most
codon-context Targeted Somatic Mutation (TSM) patterns observed in immunoglobulin
(Ig) somatic hypermutation (SHM), and in cancer exomes following Ig-SHM-like
responses. TSM refers to the process of somatic mutagenesis involving deamination
events that results on a dominant type of mutation (e.g., C-to-T), and co
incident at a particular motif (e.g., WRC), and preferentially targeting the
first, second or third nucleotide position within the mutated codon (e.g. MC1,
MC2 or MC3, read 5-prime to 3-prime). It is now widely accepted that if left
uncorrected, the accumulation of uncorrected TSMs involving the deaminases, may
lead to a diagnosis of cancer or other degenerative disease. Our hypothesis is
that many missense, nonsense and synonymous single nucleotide polymorphisms
(SNPs) associated with clinically significant diseases may have arisen in the
population by similar highly targeted deamination events. The OMIM database was
searched for disease-associated SNPs on the X chromosome, and for all
chromosomes. The nucleotide substitution patterns for disease-associated SNPs
were analyzed by the TSM method to identify the likely deaminase source for C-to
U (C-to-T/G-to-A) and A-to-I (A-to-G/T-to-C) derived gene mutations
preferentially targeting known sequence motifs associated with the deaminases:
AID, APOBEC3G, APOBEC3B and ADAR 1/2. Of the 789 OMIM SNPs analysed. In both data
sets, the mutation targeting preferences within the mutated codon reveal a
statistically significant bias (p < 0.001). The results imply that a deamination
of C-site and A-site targets are written into the human germline for the
chromosome wide exomic SNPs analysed. This is consistent with previously observed
mutation patterns arising in cancer genomes and hypermutated Ig genes during SHM.
The results imply that similar types of deaminase-mediated molecular processes
that occur in somatic hypermutation and cancer, may be contributing causative
drivers of human exomic SNPs.
PMID- 29957489
TI - New monoterpenoid by biotransformation of thymoquinone using Aspergillus niger.
AB - Microbial transformation of thymoquinone (5-isopropyl-2-methyl-cyclohexa-2,5
diene-1,4-dione) (1) by suspended cell-cultures of the plant pathogenic fungus
Aspergillus niger resulted in the production of three metabolites. These
metabolites were identified as 5-isopropyl-2-methyloxepin-1-one (2), 3-hydroxy-5
isopropyl-2-methylcyclohexa-2,5-diene-1,4-dione (3), and 5-isopropyl-2
methylbenzene-1,4-diol (4) by different spectroscopic methods. Metabolite 2 was
found to be a new compound. Compound 4 showed a potent antioxidant activity.
PMID- 29957490
TI - Lambertellin from Pycnoporus sanguineus MUCL 51321 and its anti-inflammatory
effect via modulation of MAPK and NF-kappaB signaling pathways.
AB - Lambertellin (1) and ergosta-5,7,22-trien-3-ol (2) were isolated from the solid
rice fermentation of the plant pathogenic fungus Pycnoporus sanguineus MUCL
51321. Their structures were elucidated using comprehensive spectroscopic
methods. The isolated compounds were tested on lipopolysaccharide (LPS)
stimulated RAW 264.7 macrophage cells. Lambertellin (1) exhibited promising
inhibitory activity against nitric oxide (NO) production with IC50 value of 3.19
uM, and it significantly inhibited the expression of inducible NO synthase (iNOS)
and cyclooxygenase 2 (COX-2). Lambertellin (1) also decreased the expression of
pro-inflammatory cytokines IL-6 and IL-1beta. The study of the mechanistic
pathways revealed that lambertellin (1) exerts its anti-inflammatory effect in
LPS-stimulated RAW 264.7 macrophage cells by modulating the activation of the
mitogen activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB)
signaling pathways. Therefore, lambertellin (1) could be a promising lead
compound for the development of new anti-inflammatory drugs.
PMID- 29957491
TI - Comparative study of home and community participation among children with and
without cerebral palsy.
AB - BACKGROUND: Children with cerebral palsy (CP) are at increased risk of reduced
participation. Parental evaluation of child's participation is often the decision
making factor in the process of special education and/or rehabilitation. AIMS:
Examine and compare home and community participation of children with CP and
typical development (TD) and the associations between their parents' desire for
change and participation dimensions in both settings. METHODS AND PROCEDURES:
This cross-sectional study included a convenience sample of 110 children with CP
(55% males; mean age 12.7 years) and 134 children with TD (49% males; mean age
12.1 years). The Participation and Environment Measure for Children and Youth
(PEM-CY) was used. OUTCOMES AND RESULTS: Home and community participation and
environmental supportiveness of children with CP were lower compared to children
with TD (p < .001, family income controlled). The effect sizes indicated that
there may be no clinically important difference in participation frequency.
Parents of children with CP desired change if participation was less diverse at
home, less frequent in the community, or if involvement was lower in both
settings (environmental supportiveness and income controlled). CONCLUSIONS AND
IMPLICATIONS: At home, parents expressed a desire for change more intensely
through the range of activities, while parents of children with TD emphasized
participation frequency. In the community, parents of children with CP equally
perceived participation diversity and focused more on frequency and involvement.
PMID- 29957492
TI - A meta-analysis of group Cognitive Behavioral Therapy (CBT) interventions for
adolescents with depression.
AB - The aim of this meta-analysis was to systematically examine the short- and long
term effects of group Cognitive Behavioral Therapy (CBT) for adolescent
depression and to examine the role of various moderators of the reported effect
sizes. A comprehensive literature search of relevant randomized-controlled trials
identified 23 studies containing 49 post-intervention and 56 follow-up
comparisons. Standardized mean differences (SMD) were calculated both for post
intervention and follow-up. A three-level random effects approach was used to
model the dependent effect sizes. Group CBT was more efficacious than control
conditions both at post-intervention (SMD = -0.28, 95% CI [-0.36, -0.19]) and at
follow-up (SMD = -0.21, 95% CI [-0.30, -0.11]). Having an inactive control group
was associated with a larger post-intervention effect size, while having a longer
follow-up duration was associated with a smaller follow-up effect size. Even
though the effect sizes are low, research suggests that group CBT is a
significant treatment for adolescent depression.
PMID- 29957493
TI - Are media literacy interventions effective at changing attitudes and intentions
towards risky health behaviors in adolescents? A meta-analytic review.
AB - Youth are inundated with media products promoting risky health behaviors (RHBs),
including substance use and risky sexual activity. Media literacy interventions
emphasize critical media consumption to decrease RHBs. However, it is unclear
whether they positively influence attitudes and behavioral intentions towards
RHBs. We conducted meta-analyses of 15 studies (N = 5000) testing intervention
effectiveness on media literacy skills and 20 studies (N = 9177) testing
effectiveness on attitudes and intentions towards RHBs. We found positive effects
on media literacy skills (Hedge's g = .417, [95% CI, .29-.54]) and attitudes and
intentions (Hedge's g = .100 [95% CI, .01-.19]). Intervention medium and target
behavior moderated intervention success on attitudes and intentions, but no
moderators emerged for media literacy skills. These interventions produce
positive effects on media literacy skills and positive but smaller effects on
attitudes and behavioral intentions, depending on medium and target behaviour.
Implications for adolescent health initiatives are discussed.
PMID- 29957494
TI - Alcohol expectancy profile in late childhood with alcohol drinking and purchasing
behaviors in adolescence.
AB - BACKGROUND: The study aims to (i) identify the evolving profile of endorsed
alcohol expectancies (AEs) during the transition from late childhood into early
adolescence, and (ii) examine the connection between such profiles and subsequent
alcohol drinking and purchasing in adolescence. METHODS: A prospective cohort of
928 sixth graders was recruited from 17 elementary schools in northern Taiwan in
2006 with follow-ups conducted in seventh and eighth grade. Information
concerning AEs, individual characteristics, and social attributes were collected
by self-administered questionnaires at baseline and in seventh grade; drinking
behaviors and alcohol purchasing were assessed in eighth grade. Longitudinal
latent profile and survey regression analyses were used to evaluate association
estimates. RESULTS: Three distinct profiles of positive AEs were identified:
stably low (37%), stably high (35%), and increasing (28%). Regardless of
childhood-onset alcohol experience, endorsing the stably high-profile AEs was
associated with increased drinking occasions (adjusted relative risk [aRR] =
1.49, 95% CI = 1.24-1.80), and having the increasing-profile AEs may elevate the
likelihood of alcohol purchase in adolescence (adjusted odd ratio [aOR] = 2.57,
95% CI = 1.33-4.96). Additionally, parental drinking was the most influential
social factor for drinking occasions (aRR = 1.43) whereas peer drinking was
prominent for alcohol purchasing (aOR = 3.06). CONCLUSIONS: The evolving profile
of alcohol expectancy in late childhood may predict alcohol drinking occasion and
purchasing behaviors in adolescence. Underage drinking prevention efforts should
target not only pro-alcohol social environments but also cognitive constructs
(e.g., alcohol expectancy).
PMID- 29957495
TI - Exploring the oxidative, antimicrobial and genomic properties of Campylobacter
jejuni strains isolated from poultry.
AB - Campylobacter jejuni is the leading cause of food-borne bacterial enteritis in
humans, with contaminated poultry products considered the main source of
infection. To survive the food chain, C. jejuni utilizes multiple defense
mechanisms that counter oxidative and aerobic stresses. In this study, we
phenotypically characterised 63 C. jejuni strains with oxidative stress survival
and antimicrobial susceptibility testing to investigate correlations between
these two phenotypes against the source of the strains and the presence of the
MarR regulators RrpA and RrpB which have a role in regulating the response to
oxidative and aerobic stress. C. jejuni strains isolated from meat and neck skin
displayed the highest resistance to oxidative stress. In addition, C. jejuni
strains that have an rrpA+rrpB- profile exhibit increased resistance to oxidative
stress and to antimicrobials. Here we establish a preliminary link between the
distribution of RrpA and RrpB and the increased resistance to antimicrobials.
This study provides insight into how the genotypic make up of C. jejuni can
influence the ability of the bacterium to survive within areas of high oxygen
stress, such as the food chain, and subsequently can have a potential negative
impact on human health.
PMID- 29957496
TI - Investigation of the interaction of allergens of Glycine max with IgE-antibody
for designing of peptidomimetics based anti-allergen.
AB - Allergen induced IgE dependent type I hypersensitivity is the main cause of the
allergy, which would be a burden on medical setup in coming years. Allergens of
Glycine max have been isolated, and their disease relationships are documented.
Therefore, it becomes important to investigate the interaction of different
allergens of Glycine max with IgE and also screen suitable therapeutics to
prevent this interaction. The amino acid sequences of all allergens of Glycine
max and their isoallergens have been taken, and 3D structure of allergens (Gly m
3, Gly m 4, Gly m 5, Gly m 6 and Gly m 8) and their isoallergens were generated
using Modeller v9.17. The modeled structures were further validated using PSVS,
ProSA, RAMPAGE, and PDBsum. HL domain of Fab region of human IgE (PDBID: 2R56)
was generated using UCSFchimera. The HL domain was minimized by Schrodinger
software using the OPLS_2005 force field. SiteMap identified epitope binding site
of the minimized domain. All the predicted epitopes of different allergens were
docked to the binding site of HL domain using the Patchdock server. We have also
designed a peptidomimetics based inhibitor targeted at interaction interface of
Gly m8 and IgE, using in-silico virtual screening, molecular mechanics, and
molecular dynamics simulation studies. These studies identified BDE32166344 ((N
(1-{[1-(1-aminocyclopentanecarbonyl)-3-hydroxypyrrolidin-3-yl]methyl}piperidin-4
yl)acetamide) as a peptidomimetics based lead with binding energy of -72.77
kcal/mol. Therefore, the present study investigates the interaction between
different Gly m allergens and IgE antibody and identifies peptidomimetics based
lead that might be developed as a suitable therapeutics against allergy caused by
allergen of Glycine max.
PMID- 29957497
TI - Photochemical response of parsley (Petroselinum crispum (Mill.) Fuss) grown under
red light: The effect on the essential oil composition and yield.
AB - The effect of different wavelengths on plants morphological characters has been
widely described, but also the chemical composition of the essential oil is
influenced by the lighting conditions in which they are grown. In the present
study, the effect of both the enrichment (reverse Emerson effect) and the
monochromatic lighting treatments with red light has been evaluated on the
essential oil compositions of parsley (Petroselinum crispum (Mill.) Fuss).
Multivariate statistical analysis was performed on the results, with both the
hierarchical cluster and principal component analyses. Whilst the red-enrichment
of the light spectrum did not induce major changes in the essential oil
composition, the end of the day monochromatic red (660 nm) treatment caused a
chemotype switch in the essential oil and relevant differences in the overall
composition, with an increment of the relative abundance of oxygenated compounds,
coupled with a relevant decrement in the abundance of phenylpropanoids. The
extraction yields remained unchanged in all the three tested conditions of light
(control, red-enriched and monochromatic red). Different lighting conditions
could be used as a tool to modulate the compounds present in the essential oil,
but further studies would be advisable to assess the effects on different species
and chemical classes of compounds.
PMID- 29957498
TI - Photosensitization of Chinese hamster V79 cells to photoactivated alpha
terthienyl involving membrane damage and oxidative stress.
AB - Photosensitization of V79 Chinese hamster lung fibroblasts was tested to
investigate if the cells can fit the photoactive effect of alpha-terthienyl for
safety application. Using 15-min photoirradiation of a black light (320-400 nm,
40 W), alpha-terthienyl was significantly photoactivated and caused V79 cells to
be shrinkage, detachment and necrosis. The photoactivated alpha-terthienyl played
a concentration-dependent stress to decrease cell survival and to induce cell
death with median inhibitory concentration (IC50) as 4.78 MUg/ml. Cell viability
in MTT assays also fell down to 10.58% of the control in the treatment of 10.0
MUg/ml photoactivated alpha-terthienyl. As the irradiation time prolonged and the
concentration of photoactivated alpha-terthienyl increased, cell death increased
significantly, the intracellular level of reactive oxygen species (ROS) and the
content of extracellular malondialdehyde were gradually increased. The changes of
peroxidase, superoxide dismutase and catalase activities in V79 cells were
positively responsive to the oxidative stress caused by photoactivated alpha
terthienyl. Moreover, using non-photosensitizing condition, the increased cell
death and oxidative stress in the treatment of alpha-terthienyl at >7.0 MUg/ml
were also observed. The results showed the maladjustment response of V79 cells
with membrane damage and cell death, clearly demonstrating the photosensitization
of animal cells to the photoactivated cytotoxic effect of alpha-terthienyl.
PMID- 29957499
TI - Visible light-induced biocidal activities and mechanistic study of neutral
porphyrin derivatives against S. aureus and E. coli.
AB - Positive charged porphyrins have long been regarded as effective biocidal agents,
however neutral porphyrins have rarely been studied in their ability
photoinactivating microbials, and the structure-activity relationship such as
correlation of electronic effect and biocidal activity of porphyrins still
remains unclear. Herein, four neutral porphyrins with various electronic effects
were selected to undergo light-induced biocidal processes. It turned out that the
TPPOH and TPPNH2 with electron-donating groups NH2 and OH, respectively,
exhibited much more powerful light-induced biocidal activities against E. coli
and S. aureus than TPP and TPPNO2 with electron-withdrawing group NO2. This
phenomenon suggested that neutral porphyrins may be treated as a new class of
biocidal agents and functional groups with various electronic effects on
porphyrins can dramatically affect porphyrins' light-induced biocidal activities.
Mechanistic studies demonstrate that despite a better light-induced antibacterial
ability of TPPOH, its singlet oxygen generation efficacy is a little lower than
that of TPPNH2, together with charge characteristics and lipophilicity, it is
clear that (1) the oxidative species singlet oxygen and ROS played the key role
in the photo-activated antimicrobial processes of porphyrins, and (2) higher
singlet oxygen or ROS yields of TPPOH and TPPNH2 may originate from their
structural characteristics, namely electron-donating groups OH or NH2, and (3) a
synergistic effect of all other factors including the electrostatic and
hydrophobic effects must involve in the process and cooperatively determine their
biocidal activities.
PMID- 29957500
TI - Effects of carbon and silicon nanotubes and carbon nanofibers on marine
microalgae Heterosigma akashiwo.
AB - The effect of carbon and silicon nanotubes (CNTs and SiNTs) and carbon nanofibers
(CNFs) to microscopic marine algae Heterosigma akashiwo was studied, using algal
growth inhibition for 3 days (acute effect) and 7 days (chronic effect) as
toxicity endpoints. The criterion of the toxic effect was the statistically
significant reduction of the number of algal cells in the exposed samples
compared to the control. Samples did not demonstrate toxic effects at doses 1
mg/l and 10 mg/l. CNTs and SiNTs samples at 100 mg/l exhibited both acute and
chronic toxic effects. We assume that the main cause of cell death in these
samples was related to the mechanical damage of cell integrity. CNFs at
concentrations of 100 mg/l did not inhibit algal growth, but cells with irregular
shapes were observed, which were not observed after exposure to CNTs and SiNTs.
Nickel impurities present in CNFs samples are presumably the main cause of
observed cell deformations.
PMID- 29957501
TI - Associations between urinary cotinine and symptoms of attention
deficit/hyperactivity disorder and autism spectrum disorder.
AB - BACKGROUND: The present study investigated associations between urinary cotinine
levels as a biomarker of secondhand smoke exposure and symptoms of attention
deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).
METHODS: A total of 520 child participants (200 with ADHD, 67 with ASD, and 253
normal control subjects) were assessed using the Korean version of the ADHD
rating scale (K-ARS), Autism spectrum screening questionnaire (ASSQ), and
Behavioral Assessment System for Children, second edition (BASC-2). The Korean
version of the computer-based continuous performance test was used to assess
cognitive function. Urinary cotinine was evaluated as a biomarker of secondhand
smoke exposure. RESULTS: Urinary cotinine levels were significantly and
positively associated with K-ARS score (B = 4.00, p < 0.001), ASSQ score (B =
1.71, p = 0.030), the behavioral problem subscales of the BASC-2 (B = 1.68-3.52,
p < 0.001-0.045), and omission and commission errors in the continuous
performance test (B = 6.21-8.42, p < 0.001-0.019). Urinary cotinine levels were
also associated with the increased odds ratio of ADHD (OR = 1.55, 95% CI 1.05
2.30, p = 0.028) and ASD (OR = 1.89, 95% CI 1.12-3.21, p = 0.018). CONCLUSION:
Urinary cotinine levels were associated with lower behavioral adaptation and
cognitive function and increased odds ratios of ADHD and ASD, indicating a
negative effect of secondhand smoke exposure on the symptomatic manifestation of
ADHD and ASD.
PMID- 29957502
TI - Spatial modeling of daily concentrations of ground-level ozone in Montreal,
Canada: A comparison of geostatistical approaches.
AB - Ground-level ozone (O3) is a powerful oxidizing agent and a harmful pollutant
affecting human health, forests and crops. Estimating O3 exposure is a challenge
because it exhibits complex spatiotemporal patterns. The aim in this study was to
provide high-resolution maps (100 * 100 m) of O3 for the metropolitan area of
Montreal, Canada. We assessed the kriging with external drift (KED) model to
estimate O3 concentration by synoptic weather classes for 2010. We compared these
results with ordinary kriging (OK), and a simple average of 12 monitoring
stations. We also compared the estimates obtained for the 2010 summer with those
from a Bayesian maximum entropy (BME) model reported in the literature (Adam
Poupart et al., 2014). The KED model with road and vegetation density as
covariates showed good performance for all six synoptic classes (daily R2
estimates ranging from 0.77 to 0.92 and RMSE from 2.79 to 3.37 ppb). For the
summer of 2010, the model using KED demonstrated the best results (R2 = 0.92;
RMSE = 3.14 ppb), followed by the OK model (R2 = 0.85, RMSE = 4 ppb). Our results
showed that errors appear to be substantially reduced with the KED model. This
may increase our capacity of linking O3 levels to health problems by means of
improved assessments of ambient exposures. However, future work integrating the
temporal dependency in the data is needed to not overstate the performance of the
KED model.
PMID- 29957503
TI - Photocatalytic inactivation of Vibrio fischeri using Fe2O3-TiO2-based
nanoparticles.
AB - Biofouling is a major problem in water membrane processes, especially in seawater
reverse osmosis plants. Inactivation of Vibrio fischeri (a well-known marine
bacterium forming biofilm) through photocatalysis via visible light was
investigated in this work using active Fe2O3-TiO2 nanoparticles. Five Fe2O3-TiO2
photocatalysts with different weight percentage of Fe2O3 (0-5 wt%) were
synthesized using an ultrasonic-assisted co-precipitation method. The
photocatalysts were characterized by powder X-ray diffraction (XRD), BET surface
area, transmission electron AE (TEM) plus selected area electron diffraction
(SAED) patterns, scanning electron microscopy (SEM), energy-dispersive X-ray
spectroscopy (EDX) and diffuse-reflectance spectroscopy (DRS). Based on the
design of experiments, the synthesized photocatalysts were tested for
inactivation of V. fischeri under visible light irradiation at different
temperatures (25-35 degrees C) and different photocatalyst dosage (0.1-2 g/L).
The photocatalytic microbial inactivation experiments were performed in
artificial seawater appropriate for growth of the marine bacterium. The results
revealed that the highest inactivation efficiency of V. fischeri was achieved
when 1 g/L of 2.5 wt% Fe2O3-TiO2 were used, at 35 degrees C. Photocatalytic
inactivation of microorganisms using visible light-driven Fe2O3-TiO2
photocatalysts, could introduce an innovative green method in pretreatment units
of reverse osmosis plants to control the membrane biofouling.
PMID- 29957505
TI - Odor mitigation and bacterial community dynamics in on-site biocovers at a
sanitary landfill in South Korea.
AB - Unpleasant odors emitted from landfills have been caused environmental and
societal problems. For odor abatement, two pilot-scale biocovers were installed
at a sanitary landfill site in South Korea. Biocovers PBC1 and PBC2 comprised a
soil mixture with different ratios of earthworm casts as an inoculum source and
were operated for 240 days. Their odor removal efficiencies were evaluated, and
their bacterial community structures were characterized using pyrosequencing. In
addition, the correlation between odor removability and bacterial community
dynamics was assessed using network analysis. The removal efficiency of complex
odor intensity in the two biocovers ranged from 81.1% to 97.8%. Removal
efficiencies of sulfur-containing odors (hydrogen sulfide, methanethiol, dimethyl
sulfide, and dimethyl disulfide), which contributed most to complex odor
intensity, were greater than 91% in both biocovers. Despite the fluctuations in
ambient temperature (-8.2 to 31.3 degrees C) and inlet complex odor intensity
(10,000-42,748 of odor dilution ratio), biocovers PBC1 and PBC2 displayed stable
deodorizing performance. A high ratio of earthworm casts as an inoculum source
led to high odor removability during the first 25 days of operation, but
different mixing ratios of earthworm casts did not significantly affect overall
odor removability. A bacterial community analysis showed that Methylobacter,
Arthrobacter, Acinetobacter, Rhodanobacter, and Pedobacter were the dominant
genera in both biocovers. Network analysis results indicated that Steroidobacter,
Cystobacter, Methylosarcina, Solirubrobacter, and Pseudoxanthomonas increased in
relative abundance with time and were major contributors to odor removal,
although these bacteria had a relatively low abundance compared to the overall
bacterial community. These data contribute to a more comprehensive understanding
of the relationship between bacterial community dynamics and deodorizing
performance in biocovers.
PMID- 29957504
TI - Multiple-metal exposure, diet, and oxidative stress in Uruguayan school children.
AB - Oxidative stress (OS) is an important consequence of exposure to toxic metals but
it is unclear to what extent low-level metal exposures contribute to OS in
children. We examined the cross-sectional association between urinary
concentrations of arsenic (As), cadmium (Cd), and lead (Pb) and urinary markers
of OS: F2-8alpha isoprostane and 8-hydroxy-2-deoxy-guanosine (8-OHdG). We also
tested effect modification by dietary intakes. Of the 211 children aged 6-8 years
living in Montevideo who were eligible for the study because they had at least
one OS marker measured via ELISA, 143 were included in a complete-case analysis.
Urinary metals were measured with inductively coupled plasma mass spectrometry
(ICP-MS: Pb, Cd) and high-performance liquid chromatography online with hydride
generation ICP-MS (As-metabolites); concentrations were log2-transformed. All
urinary markers were adjusted for specific gravity of urine. Two 24-h dietary
recalls were conducted to estimate children's dietary intakes, including total
fruit and vegetable consumption and vitamin C, zinc and fiber intake. Ordinary
least square (OLS) and weighted quantile sum (WQS) regressions were used to
estimate the association between metals and each OS marker as outcome. Metal
exposure was generally low: median urinary As, Cd, Pb 9.6 MUg/L, 0.06 MUg/L and
1.9 MUg/L, respectively. Median 8-isoprostane concentration was 1.1 and 8-OHdG
39.6 ng/mL. Log2-transformed urinary As concentrations were positively associated
with 8-OHdG concentrations (10.90 [3.82, 17.97]) in covariate-adjusted OLS models
which also took account of exposure to Cd and Pb. In WQS, a mixture index was
also associated with higher 8-OHdG (8.71 [1.12, 16.3] for each 25% increase in
index value), mostly driven by As exposure. There was little evidence of effect
modification by dietary antioxidants. In sum, even at low-level, As exposure is
associated with detectable oxidative damage to the DNA.
PMID- 29957508
TI - Comparing mortality risk reduction, life expectancy gains, and probability of
achieving full life span, as alternatives for presenting CVD mortality risk
reduction: A discrete choice study of framing risk and health behaviour change.
AB - The growing rate of obesity has recently required governments to divert
considerable resources in the promotion of healthy lifestyles. We explored the
relative effectiveness in inducing healthy behaviour change of three different
communication strategies about the benefits of an intervention that reduces the
mortality risks of cardiovascular disease (CVD) and encourages respondents to
embrace healthier lifestyles. We designed a Discrete Choice Experiments
questionnaire to analyse the trade-off between lifestyles, defined in terms of
diet and exercise, and reduction in cardiovascular disease (CVD) mortality risk.
We set three ways of framing an identical benefit: (A) as a reduction in
mortality risk from cardiovascular disease, (B) as an increase in months of life
expectancy, and (C) as an increase in the probability of reaching an individual's
full lifespan. The experiment was tailored for each subject in the sample
according to his/her individual's baseline information on diet and physical
activity. During the period February 2010-July 2011, we interviewed 1008
individuals in Northern Ireland, split randomly into three samples for the three
CVD risk reduction frames. Considering the models' goodness of fit and
significance, we conclude that the most effective way of communicating these CVD
health benefits is using an increase in life expectancy, since with this frame
individuals are more inclined to state that they would change to a healthier
lifestyle.
PMID- 29957507
TI - Plasma and urine metabolite profiling reveals the protective effect of
Clinacanthus nutans in an ovalbumin-induced anaphylaxis model: 1H-NMR
metabolomics approach.
AB - The present study sought to identify the key biomarkers and pathways involved in
the induction of allergic sensitization to ovalbumin and to elucidate the
potential anti-anaphylaxis property of Clinacanthus nutans (Burm. f.) Lindau
water leaf extract, a Southeast Asia herb in an in vivo ovalbumin-induced active
systemic anaphylaxis model evaluated by 1H-NMR metabolomics. The results revealed
that carbohydrate metabolism (glucose, myo-inositol, galactarate) and lipid
metabolism (glycerol, choline, sn-glycero-3-phosphocholine) are the key
requisites for the induction of anaphylaxis reaction. Sensitized rats treated
with 2000 mg/kg bw C. nutans extract before ovalbumin challenge showed a positive
correlation with the normal group and was negatively related to the induced
group. Further 1H-NMR analysis in complement with Kyoto Encyclopedia of Genes and
Genomes (KEGG) reveals the protective effect of C. nutans extract against
ovalbumin-induced anaphylaxis through the down-regulation of lipid metabolism
(choline, sn-glycero-3-phosphocholine), carbohydrate and signal transduction
system (glucose, myo-inositol, galactarate) and up-regulation of citrate cycle
intermediates (citrate, 2-oxoglutarate, succinate), propanoate metabolism (1,2
propanediol), amino acid metabolism (betaine, N,N-dimethylglycine,
methylguanidine, valine) and nucleotide metabolism (malonate, allantoin). In
summary, this study reports for the first time, C. nutans water extract is a
potential anti-anaphylactic agent and 1H-NMR metabolomics is a great alternative
analytical tool to explicate the mechanism of action of anaphylaxis.
PMID- 29957506
TI - Associations between environmental quality and adult asthma prevalence in medical
claims data.
AB - As of 2014, approximately 7.4% of U.S. adults had current asthma. The etiology of
asthma is complex, involving genetics, behavior, and environmental factors. To
explore the association between cumulative environmental quality and asthma
prevalence in U.S. adults, we linked the U.S. Environmental Protection Agency's
Environmental Quality Index (EQI) to the MarketScan(r) Commercial Claims and
Encounters Database. The EQI is a summary measure of five environmental domains
(air, water, land, built, sociodemographic). We defined asthma as having at least
2 claims during the study period, 2003-2013. We used a Bayesian approach with non
informative priors, implementing mixed-effects regression modeling with a Poisson
link function. Fixed effects variables were EQI, sex, race, and age. Random
effects were counties. We modeled quintiles of the EQI comparing higher quintiles
(worse quality) to lowest quintile (best quality) to estimate prevalence ratios
(PR) and credible intervals (CIs). We estimated associations using the cumulative
EQI and domain-specific EQIs; we assessed U.S. overall (non-stratified) as well
as stratified by rural-urban continuum codes (RUCC) to assess rural/urban
heterogeneity. Among the 71,577,118 U.S. adults with medical claims who could be
geocoded to county of residence, 1,147,564 (1.6%) met the asthma definition.
Worse environmental quality was associated with increased asthma prevalence using
the non-RUCC-stratified cumulative EQI, comparing the worst to best EQI quintile
(PR:1.27; 95% CI: 1.21, 1.34). Patterns varied among different EQI domains, as
well as by rural/urban status. Poor environmental quality may increase asthma
prevalence, but domain-specific drivers may operate differently depending on
rural/urban status.
PMID- 29957509
TI - Low endocan levels are predictive of Acute Respiratory Distress Syndrome in
severe sepsis and septic shock.
AB - PURPOSE: Endocan is a circulating proteoglycan measured at high blood levels
during severe sepsis, with a likely lung anti-inflammatory function. The aim of
this study was to assess whether paradoxically low endocan levels at Intensive
Care Unit (ICU) admission could predict Acute Respiratory Distress Syndrome
(ARDS) within 72 h in severe septic patients. MATERIALS AND METHODS: Patients
admitted for severe sepsis in the ICU of a French University Hospital were
included in a prospective single-center observational study between October 2014
and March 2016. RESULTS: 72 patients admitted in ICU for severe sepsis were
included. Endocan blood values at inclusion were significantly lower in patients
who developed an ARDS at 72 h (p < 0.001). For endocan blood values > 5.36 ng/mL,
the adjusted OR for development of ARDS at 72 h was of 0.001 (95% CI 0-0.215; p =
0.011). In our cohort, an endocan value < 2.54 ng/mL predicted ARDS at 72 h with
a positive predictive value of 1 (Sp = 1 (95% CI 0.94-1)). CONCLUSIONS: In a
cohort of severe septic patients, we observed that low blood levels of endocan at
ICU admission were predictive of ARDS at 72 h.
PMID- 29957510
TI - Bedside percutaneous dilatational tracheostomy in patients outside the ICU: a
single-center experience.
AB - PURPOSE: To assess the safety of medical-ward bedside percutaneous dilatational
tracheostomy (GWB-PDT). MATERIALS AND METHODS: A retrospective study of all
patients who underwent elective GWB-PDT between 2009 and 2015. A joint
otolaryngology-ICU team performed all GWB-PDTs. The patients were followed until
decannulation, discharge or death. Complications were divided into early (within
24 h) and late, and into minor and major. RESULTS: Two hundred and fifty six
patients were included in the study. The mean age was 77.7 +/- 11.8 Medical
history included cardiac comorbidities (42.6%) and cerebrovascular accidents
(34.4%). Overall, 48 patients (18.9%) had 60 complications, of which 70% (42/60)
were minor (13 early; 29 late complications). Fifteen patients (5.9%) had major
complications. Eight patients had early major complications (loss of airway - two
patients [0.8%], pneumothorax - two patients [0.8%], resuscitation - one patient
[0.4%], and a single patient (0.4%) died within 24 h following PDT). Two
additional patients (0.8%) underwent conversion to an open tracheostomy. Seven
patients had late complications (airway complications in six patients [2.3%] and
major bleeding in a single patient [0.4%]). Of the seven patients with late major
complications, three had two major complications. Half of the complications
occurred by POD 3. CONCLUSION: GWB-PDT is a feasible and safe solution for
tracheostomies in general-ward ventilated patients.
PMID- 29957511
TI - The utility of elliptical Fourier analysis for estimating ancestry and sex from
lateral skull photographs.
AB - Current quantitative methods for estimating ancestry and sex from skulls
typically require substantial manual data collection and specialized recording
equipment, which can limit analysis to the laboratory. This limitation could be
addressed by establishing a faster, more user-friendly, and automatic data
protocol as investigated in the current study using elliptical Fourier analysis
(EFA). Ancestry and sex were estimated using outlines acquired from standardized
photographs of the skull in norma lateralis (left side). In this investigation,
training samples comprised anatomical specimens from five collections: the Hamann
Todd Human Osteological Collection, WM Bass Donated Skeletal Collection, Robert
J. Terry Anatomical Skeletal Collection, Khon Kaen Osteological Collection, and
Chiba Bone Collection. Groups were defined as Black American female (n=87), Black
American male (n=109), Japanese male (n=59), Thai female (n=39), Thai male
(n=47), White American female (n=97), and White American male (n=134). EFA was
conducted on partial Procrustes-aligned skull outline coordinates, before
extracting principal components and using linear discriminant analysis for group
assignment. Classification accuracy was determined using the 5-fold cross
validation protocol. Ancestry and sex were classified correctly 73% of the time
when all seven reference samples were used. When only Black and White Americans
were retained in the reference sample with sex pooled, they were correctly
classified 94% of the time. Accuracy of out-of-group ancestry and sex estimation
was evaluated using nine White American males from the Defense POW/MIA Accounting
Agency Laboratory. A seven-way comparison with all reference samples for
estimating both ancestry and sex achieved 89% (8/9) correct classifications, with
one misclassification as White American female. These out-of-group results, along
with initial training group accuracies, indicate that lateral skull outlines can
be used to successfully estimate ancestry and sex with similar accuracy to other
methods, and set the basis for future cross-validation testing. Further, the
reliance on a single easy-to-take photograph and user-friendly open-source R
script facilitates easy application and field use. The protocol is freely
available from CRANIOFACIALidentification.com as the SkullProfiler script.
PMID- 29957512
TI - Development and application of a method for ivory dating by analyzing
radioisotopes to distinguish legal from illegal ivory.
AB - The age determination of elephant ivory provides necessary and crucial
information for all criminal prosecution authorities enforcing the Convention on
International Trade in Endangered Species of Wild Fauna and Flora. The knowledge
of the age of ivory allows to distinguish between pre-convention, hence legal
material and ivory deriving from recent, illegal poaching incidents. The commonly
applied method to determine the age of ivory is radiocarbon dating in the form of
bomb pulse dating, which however will fade out soon. This work provides an
enhancement of the radiocarbon dating method by supplementary determination of
the isotope profile of 90-Sr and the two thorium isotopes 228-Th and 232-Th. This
combined analysis allows for a precise and unambiguous age determination of
ivory. We provided calibration curves for all involved radionuclides by analyzing
ivory samples with known age and investigated a new method for the extraction of
strontium from ivory.
PMID- 29957513
TI - A comparative study to investigate the effect of orthodontic treatment on the
uniqueness of the human anterior dentition.
AB - AIM: The human dentition contains many features which can be used to identify an
individual from the dentition or from bite marks created and bite mark evidence
may be used to link a suspect to a crime. The aim of this research was to
investigate the effect of orthodontic treatment on the uniqueness of the human
anterior dentition by comparison of the number of dental shape matches between
pre- and post-treatment dental casts for a group of patients who have undergone
orthodontic treatment (dental braces) to improve the alignment of their teeth.
METHOD: This comparative study utilised pre- and post-orthodontic treatment
dental casts from 36 patients. The dental casts were scanned and the anterior 6
teeth landmarked with 24 landmarks in total. The dental casts were divided into 4
groups: pre-orthodontic upper jaw (maxillary) and lower jaw (mandibular) and post
orthodontic maxillary and mandibular. Partial and full Procrustes analyses were
undertaken to investigate the similarity between dental casts within each group
and whether any of the comparisons were similar enough to be classified as a
match. A landmarking repeatability study performed on a set of digitised dental
casts determined the error of the landmarking procedure and allowed a proposed
match threshold to be established. RESULTS: Orthodontic treatment reduced the
uniqueness, and increased the similarity, between dentitions, as evidenced by a
reduction in the maximum partial Procrustes distances in the post-orthodontic
dental cast groups. None of the dental cast comparisons in the pre- or post
orthodontic maxillary or mandibular groups were classified as a match with the
partial Procrustes analysis. However, many false positive matches (between 35 and
61) were identified within the post-orthodontic maxillary and mandibular groups
using the full Procrustes analysis. CONCLUSIONS: Orthodontic treatment reduced
the uniqueness of the human anterior dentition between different patients. There
were no matches identified with the partial Procrustes analysis, but a large
number of false positive matches were identified using the full Procrustes
analysis. It is therefore proposed that full Procrustes analysis is unsuitable
for this type of work and that only partial Procrustes analysis should be
utilised.
PMID- 29957514
TI - Alcohol consumption or contamination: A preliminary study on the determination of
the ethanol origin by stable carbon isotope analysis.
AB - The origin of ethanol detected in bio-samples whether it be from the consumption
of alcoholic beverages or contamination with disinfectants has been questioned in
court cases in China recently. The stable carbon isotope naturally occurs in
carbon-containing compounds and can help determine the origin of the compound in
question. In total, 42 types of beers and 11 types of disinfectants were analyzed
by gas chromatography-isotope ratio mass spectrometry. Consumption and
contamination experiments were carried out with 6 volunteers. The delta13C values
of ethanol ranged from -29.510/00 to -18.360/00 for the beer samples, which
reflected the botanical features of C3 plants or mixtures of C3 and C4 plants.
The delta13C values of ethanol ranged from -17.70/00 to -14.40/00 for
disinfectants, which reflected the different origins of ethanol in disinfectants
from those in beer. The delta13C value did not change in vivo after being
consumed within the time limit used in this study. These characteristics of the
delta13C values will facilitate to interpret whether the ethanol detected in bio
samples originated from consumption or contamination.
PMID- 29957515
TI - Listening effort during speech perception enhances auditory and lexical
processing for non-native listeners and accents.
AB - Speech communication in a non-native language (L2) can feel effortful, and the
present study suggests that this effort affects both auditory and lexical
processing. EEG recordings (electroencephalography) were made from native English
(L1) and Korean listeners while they listened to English sentences spoken with
two accents (English and Korean) in the presence of a distracting talker. Neural
entrainment (i.e., phase locking between the EEG recording and the speech
amplitude envelope) was measured for target and distractor talkers. L2 listeners
had relatively greater entrainment for target talkers than did L1 listeners,
likely because their difficulty with L2 speech recognition caused them to focus
more attention on the speech signal. N400 was measured for the final word in each
sentence, and L2 listeners had greater lexical processing in high-predictability
sentences than did L1 listeners. L1 listeners had greater target-talker
entrainment when listening to the more difficult L2 accent than their own L1
accent, and similarly had larger N400 responses for the L2 accent. It thus
appears that the increased effort of L2 listeners, as well as L1 listeners
understanding L2 speech, modulates their auditory and lexical processing during
speech recognition. This may provide a mechanism to compensate for their
perceptual challenges under adverse conditions.
PMID- 29957516
TI - Meta-ethics and the mortality: Mortality salience leads people to adopt a less
subjectivist morality.
AB - Although lay notions in normative ethics have previously been investigated within
the framework of the dual-process interpretation of the terror management theory
(TMT), meta-ethical beliefs (subjective vs. objective morality) have not been
previously investigated within the same framework. In the present research, we
primed mortality salience, shown to impair reasoning performance in previous
studies, to see whether it inhibits subjectivist moral judgments in three
separate experiments. In Experiment 3, we also investigated whether impaired
reasoning performance indeed mediates the effect of mortality salience on
subjectivism. The results of the three experiments consistently showed that
people in the mortality salience group reported significantly less subjectivist
responses than the control group, and impaired reasoning performance partially
mediates it. Overall, the results are consistent with the dual-process
interpretation of TMT and suggest that not only normative but also meta-ethical
judgments can be explained by this model.
PMID- 29957517
TI - Acute and (sub)chronic toxicity of the neonicotinoid imidacloprid on Chironomus
riparius.
AB - Impacts of neonicotinoids on non-target insects, including aquatic species, may
significantly influence ecosystem structure and functioning. The present study
investigated the sensitivity of Chironomus riparius to imidacloprid exposures
during 24-h, 10- and 28-days by assessing larval survival, growth, emergence and
oxidative stress-related parameters. C. riparius exhibited high sensitivity
compared to other model aquatic species with acute 24-h LC50 being 31.5 MUg/L and
10-days LOEC (growth) 0.625 MUg/L. A 28-days partial life cycle test demonstrated
imidacloprid effects on the emergence of C. riparius. Exposure to sublethal
concentrations during 10-days caused an imbalance in the reduced and oxidized
glutathione (GSH and GSSG), and slightly induced lipid peroxidation (increased
malondialdehyde, MDA). Our results indicate that oxidative stress may be a
relevant mechanism in the neonicotinoid toxicity, reflected in the insect
development and life cycle parameters.
PMID- 29957518
TI - Investigating the suitability of Fe0 packed-beds for water defluoridation.
AB - A commercial granular metallic iron (Fe0) specimen was used to evaluate the
suitability of Fe0 materials for removing aqueous fluoride (F-) (water
defluoridation). Experiments were performed to characterize the defluoridation
potential of the tested Fe0 as influenced by the presence of chloride (Cl-) and
bicarbonate (HCO3-) ions using tap water (H2O) as operational reference system.
Duplicate column studies were conducted for 120 days (4 months) using an initial
F- concentration of 22.5 mg L-1, columns flow rates were about 17 mL h-1. Each
column contained a reactive layer (11 cm) made up of 100 g of Fe0 in a 1:1
volumetric Fe0:sand mixture. The reactive layer was sandwiched between two layers
of the same sand. A pure sand column was used as control system. After the F-
removal experiments, the columns were flushed by methylene blue (MB) and Orange
II for 21 days. Removal studies revealed (i) no F- removal in the control system,
(ii) no F- significant removal on the Cl- system, (iii) limited F- removal in the
HCO3- system, and (iv) the best F- removal efficiency in tap water (H2O). Dye
flushing studies confirmed the ion-selective nature of the Fe0/H2O system and
demonstrated the relatively low efficiency of the same for F- removal. The
overall results challenge the prevailing perception that water defluoridation
using granular Fe0 is not possible and suggest that effective water
defluoridation in Fe0 packed-beds is pure a site-specific design issue.
PMID- 29957519
TI - Energy-efficient ultrasonic release of bacteria and particulates to facilitate
ingestion by phagotrophic algae for waste sludge treatment and algal biomass and
lipid production.
AB - Wastewater treatment generates large amounts of waste activated sludge (WAS) that
contains concentrated bacteria and particulate organics and requires costly
treatment prior to disposal. This study develops an approach to harness the
unique capability of oleaginous phagotrophic microalgae for treating WAS and
producing algal biomass and lipids. WAS ultrasonication is studied for releasing
particulates and bacteria suitable for direct ingestion by phagotrophic
microalgae, without bacterial destruction/lysis, and thus minimizing energy
requirement. Particle release into supernatant was followed by optical density at
610 nm (OD610) and volatile solid concentration (VS); OD610 correlated well with
micron-size particle count rates measured by dynamic light scattering. Microalgae
(Ochromonas danica) grew with a 7.6-h doubling time in sonication-generated WAS
supernatant alone, giving approximately 66% (w/w) cell yield from consumed VS and
~30% intracellular lipids. Effects of sonication power (P in W), WAS volume (V in
mL) and sonication duration (t in s) were studied with a 3 * 3 * 6 factorial
design. Supernatant OD610 increased with increasing P and t and decreasing V.
Multiple linear regression gave the following equation with only significant
terms: OD610TS=-0.0536+0.000592P-0.000213t+0.000003P*t+0.000274P*tV (R2 = 0.94).
Sonicating 500-mL WAS at 180 W for 240 s was selected for giving high particulate
release (~29% VS) with maximal energy efficiency, corresponding to a specific
energy input of 4320 kJ (kg TS)-1, which was much lower than the range (15,000
250,000 kJ (kg TS)-1) reported previously for WAS ultrasonication. The results
supported development of new ultrasonication-phagotrophic algae processes for WAS
treatment and algae production.
PMID- 29957520
TI - Bioaccumulation and trophic transfer of 137Cs in marine and freshwater plankton.
AB - An experimental study was conducted to investigate the trophic transfer of 137Cs
in marine and freshwater food chains, focusing on phytoplankton, zooplankton, and
planktivorous fish. Algal concentration factors were 278 in freshwater and 69 in
seawater. The weight-normalized uptake rate constants of 137Cs were similar for
both freshwater daphnids and marine copepods. Most of the 137Cs in marine
copepods was in the exoskeleton followed by polar and non-polar components. In
freshwater daphnids, 137Cs was highest in the polar fractions followed by
exoskeleton and low amounts in the non-polar components. Fish that fed on
contaminated marine copepods assimilated 137Cs with an efficiency of 88%, while
91% was assimilated from freshwater daphnids. A bioaccumulation model
demonstrated that diet accounted for <=3% of the total body burden of 137Cs in
marine zooplankton and <=12% in freshwater zooplankton, but >=99% of the total
body burden in fish. Rate constants of 137Cs loss from fish following aqueous
exposure were 0.2 d-1 and 0.4 d-1 in marine and freshwater conditions,
respectively, but only 0.06 d-1 and 0.3 d-1, respectively, following dietary
exposure. This model also indicates that trophic transfer factors from
zooplankton to fish are up to 2.2 for marine conditions and up to 0.6 for
freshwater. 137Cs is unusual among metals in that it enters marine food chains
primarily from the aqueous phase into zooplankton, from which it is highly
assimilated by fish, resulting in detectable 137Cs in fish tissues.
PMID- 29957521
TI - Different dissolved organic matter (DOM) characteristics lead to diverse atrazine
adsorption traits on the non-rhizosphere and rhizosphere soil of Pennisetum
americanum (L.) K. Schum.
AB - Plant activities might alter the environmental behavior of organic pollutants in
rhizosphere soil during phytoremediation. To further illustrate the mechanisms
underlying the varying adsorption about the different adsorbing abilities of
rhizosphere soil (RS) and non-rhizosphere soil (NRS) for the same pollutant,
atrazine was selected to investigate the adsorption traits in the NRS and RS of
Pennisetum americanum (L.) K. Schum (P. americanum), a potential phytoremediator
of atrazine pollution. Furthermore, the different fluorescence spectral
properties of the dissolved organic matter (DOM) extracted from RS and NRS when
binding with atrazine were also investigated. RS exhibited a higher atrazine
adsorption capacity than NRS, although the kinetic and isothermal properties of
atrazine adsorption onto the two kinds soil were described by a pseudo second
order model and the Freundlich model. The DOM extracted from RS showed a stronger
atrazine-binding ability than that extracted from NRS, as proven by the much more
obvious decrease in fluorescence intensity when binding with atrazine. Although
synchronous fluorescence spectra analysis suggested that both DOM types bind
atrazine using a static fluorescence quenching mechanism, Fourier transform
infrared spectroscopy showed that some distinct functional groups, which might
liable to combine with atrazine, were found in only the DOM extracted from RS.
Considering the findings mentioned above and the fact that the typical chemical
characteristics of RS were different from those of NRS, we concluded that the P.
americanum enhances the atrazine adsorption ability of RS by regulating the
chemical characteristics and atrazine-binding ability of DOM in RS.
PMID- 29957522
TI - Role of pre-corrosion of Fe0 on its efficiency in remediation systems: An
electrochemical study.
AB - The duration of in-situ generation of iron corrosion products (FeCPs) prior the
remediation process (so called "aging" of metallic iron (Fe0)), was found as the
key parameter affecting the efficiency of Fe0 for water remediation. Batch
experiments were performed in buffered solutions (pH 4.0, 4.7 and 5.5) and under
oxic conditions (presence of dissolved oxygen) using Zn2+ as probe contaminant.
The time-dependent (0-16 d) concentration changes of aqueous Fe2+ and Zn2+ were
monitored using differential pulse polarography (DPP). During the time of pre
corrosion varying from 0 to 6 d, an "induction period" of the corrosion occurs in
the first one - 2 h when no Fe2+ ion is released in the solution. After this
period, Fe2+ was identified in solution and its concentration progressively
increases up to 6 h, then starts to decrease and after 6 d nearly disappears.
Experiments with Zn2+ reveal that the most efficient Fe0 remediation occurs after
6 h of pre-corrosion. This coherence thus proves that the presence, the amount
and the age of FeCPs ("degree" of corrosion) significantly impact the removal
efficiency of Zn2+ in Fe0/H2O systems. The present study severely refute the
wording 'reactivity loss' and states that progress in designing sustainable
Fe0/H2O systems will not be achieved before the role of "active" FeCPs is
clarified.
PMID- 29957523
TI - Increased exposure to pesticides and colon cancer: Early evidence in Brazil.
AB - Environmental factors may increase colon cancer (CC) risk. It has been suggested
that pesticides could play a significant role in the etiology of this malignancy.
As agriculture is one of the mainstays of the Brazilian economy, this country has
become the largest pesticides consumer worldwide. The CC burden is also
increasing in Brazil. Herein, we examined data from the Brazilian Federal
Government to determine whether CC mortality and pesticide consumption may be
associated. Database of the Ministry of Health provided CC mortality data in
Brazil, while pesticide usage was accessed at the website of Brazilian Institute
of Environment and Renewable Natural Resources. The CC mortality in the Brazilian
states was calculated as standard mortality rates (SMR). All Bayesian analysis
was performed using a Markov chain Monte Carlo method in WinBUGS software. We
observed that CC mortality has exhibited a steady increase for more than a
decade, which correlated with the amount of sold pesticides in the country. Both
observations are concentrated in the Southern and the Southeast regions of
Brazil. Although ecological studies like ours have methodological limitations,
the current dataset suggests the possibility that pesticide exposure may be a
risk factor for CC. It warrants further investigation.
PMID- 29957524
TI - Comparing two start up strategies and the effect of temperature fluctuations on
the performance of mainstream anammox reactors.
AB - Anammox cultivated with high substrate concentration (NH4+-N, 150 mg/L; NO2--N,
200 mg/L) at 35 degrees C was first used as seed sludge to start up reactors at
35 (Ra), 20 (Rb) and 15 degrees C (Rc) with low substrate concentration (NH4+-N
30 mg/L, NO2--N 40 mg/L). The results showed that anammox activity initially
decreased in the three reactors, but that activity levels and nitrogen loading
rate (NLR) increased as the bacteria gradually adapted to the new conditions (12
30 days). Temperature and concentration shift affected anammox activity jointly.
In the process, the abundance of mRNA of the key functional genes of hdh and
nirS, changed with time but this change did not reflect the change of anammox
activity. When the reactors reached a stable state after 40 d, the effect of
temperature fluctuations was tested. The results showed that anammox adapted to
low temperatures as soon as temperature decreased (i.e., decreased from 35
degrees C to 15 degrees C). When temperature increased, 2-3 days were needed for
activity recovery. From this result, it may be concluded that reactors with low
temperatures and low substrate (mainstream) concentrations can be started up
using anammox cultivated at a higher temperature (35 degrees C) with low
substrate. Then anammox in Ra was used to start up a mainstream reactor at 15
degrees C and it was operated for 60 days. The results showed that the activity
in Ra decreased sharply to the level as that of Rc at the stable state. After the
experiment, microbiological analysis showed that the anammox was stable and that
Candidatus Kuenenia was the dominant species.
PMID- 29957525
TI - N-(1,3,4-oxadiazol-2-yl)benzamide analogs, bacteriostatic agents against
methicillin- and vancomycin-resistant bacteria.
AB - Various reports of multidrug-resistant bacteria that are immune to all available
FDA-approved drugs demand the development of novel chemical scaffolds as
antibiotics. From screening a chemical library, we identified compounds with
antibacterial activity. The most potent compounds, F6-5 and F6, inhibited growth
of various drug-resistant Gram-positive bacterial pathogens at concentrations
ranging from 1 MUg/mL to 2 MUg/mL. Both compounds were active against clinical
isolates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin
intermediate and vancomycin-resistant S. aureus (VISA and VRSA respectively) and
vancomycin-resistant Enterococcus faecalis (VRE). Resistance generation
experiments revealed that MRSA could develop resistance to the antibiotic
ciprofloxacin but not to F6. Excitingly, F6 was found to be non-toxic against
mammalian cells. In a mouse skin wound infection model, F6 was equipotent to the
antibiotic fusidic acid in reducing MRSA burden.
PMID- 29957526
TI - X-ray crystal structure guided discovery of new selective, substrate-mimicking
sirtuin 2 inhibitors that exhibit activities against non-small cell lung cancer
cells.
AB - Human sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent
deacylase, and is implicated in human diseases including cancer. Selective small
molecule inhibitors for SIRT2 are sought as chemical tools and potential
therapeutics. Here we report the X-ray crystal structure guided structure
activity relationship studies of new N-(3-(phenoxymethyl)phenyl)acetamide
derivatives with SIRT2, which led to the identification of potent, selective
SIRT2 inhibitors. Crystallographic analyses reveal that the new inhibitors act
via inducing the formation of an enlarged hydrophobic pocket and particularly
mimicking the interactions made by myristoylated-lysine substrates. The most
potent inhibitor 24a could dose-dependently elevate the acetylation level of
alpha-tubulin in the non-small cell lung cancer H441 cells, which have a high
expression level of SIRT2 as determinated by Western blotting analyses. Further
cellular assays reveal that 24a restrains cell growth mainly through inhibiting
cellular proliferation rather than inducing apoptosis. Moreover, 24a could
suppress the migration and invasion of H441 cells. These results provide an
excellent basis for further development of new potent, selective, and cell active
SIRT2 inhibitors as chemical tools and potential therapeutics for SIRT2-driven
non-small cell lung cancers.
PMID- 29957527
TI - Pakistan's lack of mental health services for children: Failing the future.
PMID- 29957528
TI - Use of opium containing herbal drug and associated mania.
PMID- 29957529
TI - The effect of combining tenderstretching and electrical stimulation on alpaca
(Vicugna pacos) meat tenderness and eating quality.
AB - The effect of combining tenderstretching (TS; carcase suspension by the pelvic
bone) with medium voltage electrical stimulation (ES) during processing on the
tenderness of alpaca muscles was investigated. Thirty-six split alpaca carcases
were randomly allocated to treatments in a 2 * 2 factorial arrangement (Achilles
hung/TS and ES/non-ES). Samples were collected from the m. longissimus thoracis
(LT), m. adductor femoris (AF), m. semimembranosus (SM), m. semitendinosus (ST)
and m. psoas major (TL) at 24 h post slaughter for shear force, sarcomere length,
collagen and myofibre (particle size) measurement. Additional samples were taken
from the m. longissimus lumborum (LL) for sensory assessment using an untrained
consumer panel. Tenderstretching reduced shear force and variability within the
alpaca AF, without negatively affecting the TL, while ES significantly improved
TL and LT tenderness. Consumers were able to detect ES treated LL, rating ES
samples higher for all sensory traits. Combining ES and TS maximizes alpaca
carcase tenderness when considered on a multiple muscle basis.
PMID- 29957530
TI - Xanthan gum-functionalised span nanoparticles for gene targeting to endothelial
cells.
AB - Endothelial cells play a critical role in many physiological processes;
therefore, there is increasing evidence that the future of many treatments for
pathologies depends on the development of endothelium-targeting systems. Thus, we
have incorporated the natural polysaccharide xanthan gum (XG) into sorbitan
monooleate nanoparticles to provide them with a hydrophilic and negatively
charged surface shell with stabilising properties and an inherent ability to
target endothelial cells. Enhanced Green Fluorescent Protein plasmid (pEGFP) was
incorporated into the nanosystem, and the protection ability and stability of
this system was confirmed. Nanoparticle cytotoxicity and transfection capacity
were successfully tested in Human Umbilical Vein Endothelial Cells (HUVECs)
before confirming their biocompatibility in vivo. Finally, biodistribution
studies after pEGFP-XG nanoparticle systemic administration to mice evidenced GFP
expression in the vascular endothelium of lung, liver and kidney, thus confirming
the potential of xanthan gum-functionalised span nanoparticles for gene targeting
to endothelial cells.
PMID- 29957531
TI - Incorporation of BMP-2 nanoparticles on the surface of a 3D-printed
hydroxyapatite scaffold using an epsilon-polycaprolactone polymer emulsion
coating method for bone tissue engineering.
AB - Hydroxyapatite (HAp)-based three-dimensional (3D) scaffolding is an excellent
method for the fabrication of complex-shaped scaffolds to reconstruct bone
defects. This study aimed at improving the osteoinductivity and compressive
strength of the HAp-based 3D scaffold for bone regeneration. Bone morphogenetic
protein-2-loaded nanoparticles (BMP-2/NPs) were prepared by a double emulsion
solvent evaporation method and incorporated onto the surface of 3D scaffolds
using epsilon-polycaprolactone (PCL) and NPs emulsion solution. The surface
morphology of the scaffold was characterized using scanning electron microscopy
and its biocompatibility and osteogenic effects evaluated in vitro using human
mesenchymal stem cells. The in vivo bone regeneration efficiency was determined
using a rabbit calvarial bone defect model. We obtained 3D HAp scaffolds with NPs
using PCL coating process. BMP-2/NPs were uniformly distributed on the scaffold
surface and BMP-2 was gradually released. Furthermore, PCL coating improved the
compressive strength of the scaffold. The cell proliferation, adhesion, and
osteogenic differentiation properties were improved with PCL_BMP-2/NPs coated
scaffold. In vivo experiments showed that the formation of new bone was
significantly higher in the PCL_BMP-2/NPs group than in the uncoated scaffold
implanted group. The coating method using PCL and NPs emulsion solutions was
useful not only to incorporate BMP-2/NPs onto the surface of the scaffold, but
also to improve the compressive strength, which enhanced bone regeneration.
PMID- 29957532
TI - Unraveling the molecular mechanism of the effects of sodium dodecyl sulfate,
salts, and sugars on amyloid fibril formation in camel IgG.
AB - Sodium dodecyl sulfate (SDS) is an anionic surfactant that can be used to
stimulate protein fibrillation in vitro. Here, we investigated the effects of SDS
on camel IgG aggregation at pH 3.5 and 7.4. SDS-induced amyloid fibril formation
in camel IgG was examined by turbidity measurements, Rayleigh scattering,
Thioflavin T (ThT) fluorescence, intrinsic fluorescence, circular dichroism (CD),
and transmission electron microscopy (TEM). The results suggest that low SDS
concentrations (0.2-2.0 mM) induce amyloid-like aggregates of camel IgG at pH
3.5, indicating an SDS/camel IgG ratio below 1000. However, in the presence of
higher concentrations of SDS (2.5-10.0 mM), amyloid fibril formation was not
observed. Furthermore, at the higher concentrations, the beta-sheet structure of
camel IgG was transformed into a alpha-helical structure. The amyloid fibril
formation was not observed in the presence of SDS at pH 7.4. Additionally, the
role of salts and sugars was evaluated in the SDS-induced aggregation process.
Interestingly, in the presence of 0.15 N of NaCl and (NH4)2SO4, SDS promoted
camel IgG aggregation up to very high concentrations of SDS (0.2-10.0 mM;
SDS/camel IgG ratio, 95-4750) and no suppression was observed. Moreover,
osmoprotectants (trehalose and sucrose) were ineffective, neither promoting nor
inhibiting the SDS-induced aggregation process. However, at pH 3.5, electrostatic
and hydrophobic interactions, and hydrogen bonds were the major contributing
factors in SDS-induced fibrillation. However, no aggregation was observed at pH
7.4 due to electrostatic repulsion between SDS and camel IgG because both of
these molecules have overall similar charges.
PMID- 29957533
TI - Emulsifying properties of ruptured microalgae cells: Barriers to lipid extraction
or promising biosurfactants?
AB - A systematic investigation of the emulsifying properties of ruptured algae cells
was performed for the first time. The slurry of ruptured algae cells was
separated into different biomass fractions, namely the cell debris, the
delipidated debris, the serum, and the lipid. The interfacial interactions of
these biomass fractions with a nonpolar solvent (e.g. hexane or hexadecane) were
characterized using pendant drop tensiometry and interfacial shear rheology. The
stability of the different emulsions (formed by the different biomass fractions)
was tested using analytical centrifugation. The extracted lipid was an excellent
surfactant that reduced the interfacial tension, however, it was not effective at
stabilizing the emulsions. The protein-rich serum produced a strong interfacial
film that stabilized the emulsions against coalescence during centrifugation. The
cell debris stabilized the emulsions to a lesser extent by adsorbing to the
droplet surface, presumably via interactions with hydrophobic extracellular
polymeric substances (EPS). However, neither the serum nor the cell debris were
very effective surfactants, and required the presence of the lipid fraction to
produce small emulsion droplets. When present together, the components exhibited
competitive interfacial adsorption, which influenced emulsion stability. In
particular, the interruption of the protein film by the presence of lipid or cell
debris reduced the stability of the emulsions. This study provides a new
mechanistic understanding of emulsification during wet lipid extraction from
microalgae that will be useful for determining strategies to improve solvent
recovery. The results also suggest potential for developing effective
bioemulsifiers or biosurfactants from fractionated microalgae biomass for
commercial application.
PMID- 29957534
TI - Preliminary analysis of the interactions between CdTe quantum dots and human
metallothionein.
AB - Metallothionein (MT) plays the important role in the detoxification of heavy
metals, protection against oxidative compounds and as a prognostic marker in the
development of tumors. It is important to find selective, stable and sensitive
tools and probes to evaluate the presence of MT in biological fluids or tissues.
QDs linked with ligands such as peptides or small molecules are a promising tool
for selective, fast, and sensitive tagging and imaging in medicine. In previous
findings, the authors proved the possibility of interaction with QDs
(particularly with CdTe) and analyzed the stability of the formed complexes
between CdTe and MT during incubation over time. Following that, an initial
analysis of the interactions between CdTe quantum dots (QDs) and human
metallothionein (MT) was performed. Complexes of mercaptosuccinic acid-covered
CdTe QDs + MT were investigated using fluorescence intensity changes along a
timeline, quenching analysis, stability interpretation based on zeta potential,
and quenching intensity. Based on the preliminary results, it appears as though
the possible interactions depend on the size of the CdTe QDs. Additionally, the
formation of complexes between CdTe and human MT likely depends mostly on
structural changes and conformational reorganization rather than on electrostatic
interactions. Both types of interactions are responsible for complex creation and
stabilization.
PMID- 29957535
TI - Numerical study of an alternative to a deuterium-tritium source in gas saturation
logging based on the inelastic gamma spectrum.
AB - In this study, we investigated the feasibility of using a D-Li7 neutron generator
to replace a deuterium-tritium (D-T) neutron generator in gas saturation logging.
The logging response and gas sensitivity of gas saturation logging based on the
inelastic gamma spectrum were simulated with the Monte Carlo method, and the
factors that influenced the gas sensitivity and inelastic gamma counts were
analyzed based on the spatial response distribution. The results showed that the
logging response based on the D-Li7 source was similar to that based on the D-T
neutron generator after calibration, which validated the feasibility of this
method. Using the D-Li7 neutron generator, the sensitivity of gas saturation was
higher when the scattering cross section of formation was not high.
PMID- 29957536
TI - The effect of pre-dose on thermally and optically stimulated luminescence from
alpha-Al2O3:C,Mg and alpha-Al2O3:C.
AB - We report the effect of pre-dose on the thermoluminescence (TL) and optically
stimulated luminescence (OSL) dose response of alpha-Al2O3:C,Mg and alpha
Al2O3:C. Before any luminescence measurement, the samples were irradiated with
different doses, namely 100, 500 and 1000 Gy to populate the deep electron traps.
This is the pre-dose. The results from TL and OSL studies are compared with
results from samples used without any pre-measurement dose. The TL glow curves
and OSL decay curves of alpha-Al2O3:C,Mg recorded after pre-doses of 100, 500 and
1000 Gy are identical to those from a sample used without any pre-dose. Further,
the TL and OSL dose response of all alpha-Al2O3:C,Mg samples are similar
regardless of pre-dose. In comparison, the TL glow curves and OSL decay curves of
alpha-Al2O3:C are influenced by pre-dose. We conclude that the differences in the
TL and OSL dose response of various pre-dosed samples of alpha-Al2O3:C are due to
the concentration of charge in the deep traps. On the other hand, owing to the
lower concentration of such deep traps in alpha-Al2O3:C,Mg, the TL or OSL dose
responses are not affected by pre-dose in this material.
PMID- 29957537
TI - Development and optimization of a novel automated loop method for production of
[11C]nicotine.
AB - A novel, rapid, and automated loop method for the synthesis of [11C]nicotine was
developed and optimized. The method involves, a reaction of the precursor, (+)
nornicotine or (-) nornicotine, with a gas-phase produced [11C]CH3I in an 800 uL
loop at 75 degrees C for 5 min followed by a semi-preparatory Reversed-Phase
High-Performance Liquid Chromatography (RP-HPLC) purification. The optimized
synthesis and purification process was complete in < 30 min and produced
[11C]nicotine with > 99.9% Radiochemical Purity (RCP), no [11C]CH3I, no (+)
nornicotine, 105 mCi/umole specific activity, 7.0 - 7.2 pH, and 16.6% ethanol.
The current method can be optimized, to reduce the ethanol content (<10%), and
can be translated to a cGMP production of [11C]nicotine for human clinical
trials.
PMID- 29957538
TI - Modelling the absorbed dose rate of the beta standard BSS2 147Pm source.
AB - The dosimetric measurements of 147Pm beta radiation beams have limitations due to
their low energy, low dose rate, great dispersion and attenuation in air or
tissue. In this work, the Monte Carlo model was developed for a 147Pm absorbed
dose rate determination. This model consists of an extrapolation chamber and a
147Pm beta radiation source. Moreover, the absorbed dose rate was determined by
experimental measurements and the MCNP Monte Carlo code was used. The relative
number of particles that crossed the radioactive source window and the particles
that crossed the extrapolation chamber entrance window were determined. The
source fluence spectrum was also determined. The results of the simulation and
the experimental calculations are in agreement with the absorbed dose rate from
the PTB calibration certificate. The results obtained are considered acceptable,
and they agree within the uncertainties. The difference between the experimental
result and that from the Monte Carlo model, compared to that from the calibration
certificate, was only 0.8% in both cases.
PMID- 29957539
TI - Efficient UV repair requires disengagement of the CSB winged helix domain from
the CSB ATPase domain.
AB - The ATP-dependent chromatin remodeler CSB is implicated in a variety of different
DNA repair mechanisms, including transcription-coupled nucleotide excision repair
(TC-NER), base excision repair and DNA double strand break (DSB) repair. However,
how CSB is regulated in these various repair processes is not well understood.
Here we report that the first 30 amino acids of CSB along with two
phosphorylation events on S10 and S158, previously reported to be required for
CSB function in homologous recombination (HR)-mediated repair, are dispensable
for repairing UV-induced DNA damage, suggesting that the regulation of CSB in
these two types of repair are carried out by distinct mechanisms. In addition, we
show that although the central ATPase domain of CSB is engaged in interactions
with both the N- and C-terminal regions, these interactions are disrupted
following UV-induced DNA damage. The UV-induced disengagement of the C-terminal
region of CSB from the ATPase domain requires two conserved amino acids W1486 and
L1488, which are thought to contribute to the hydrophobic core formation of the
winged helix domain (WHD) at its C-terminus. Failure to undergo UV-induced
dissociation of the C-terminal region of CSB from the ATPase domain is associated
with impairment in its UV-induced chromatin association, its UV-induced post
translational modification as well as cell survival. Collectively, these findings
suggest that UV-induced dissociation of CSB domain interactions is a necessary
step in repairing UV-induced DNA damage and that the WHD of CSB plays a key role
in this dissociation.
PMID- 29957541
TI - Potential endocrine-disrupting effects of metals via interference with
glucocorticoid and mineralocorticoid receptors.
AB - As a result of human activities, the pollution of metals is becoming ubiquitous
in the environment. Among various toxicological mechanisms of action, metals have
been considered as endocrine-disrupting chemicals (EDCs) through interference
with steroid receptors. However, information regarding the potential endocrine
disruption of metals on glucocorticoid receptor (GR) and mineralocorticoid
receptor (MR) is especially scarce. In this study, a total of 16 metals were
assessed for their GR/MR activities using luciferase reporter gene assay. None of
the tested metals exhibited GR or MR agonistic activity, but a total of 7 and 5
candidate metals showed obvious GR and MR antagonistic properties, respectively.
All 7 GR antagonistic metals [ BaCl2, CoCl2, CuCl2, Pb(NO3)2, LiCl, SnCl2 and
ZnCl2] inhibited glucocorticoid-responsive gene GILZ expression in J774A.1 cells.
Further investigations indicated that the 5 MR antagonistic metals [ CdCl2,
Pb(NO3)2, LiCl, MnCl2 and SnCl2] antagonized aldosterone-inhibited hepatocellular
carcinoma cell proliferation. Among these metals, Pb(NO3)2, LiCl, and SnCl2
showed both anti-glucocorticoid and anti-mineralocorticoid activities.
Comprehensive screening and evaluation of GR and MR antagonists and agonists
among metals should be considered to better understand the ecological and health
risks of metals.
PMID- 29957540
TI - Rational design of carbonaceous nanofiber/Ni-Al layered double hydroxide
nanocomposites for high-efficiency removal of heavy metals from aqueous
solutions.
AB - Heavy metal pollution of water sources has raised global environmental
sustainability concerns, calling for the development of high-performance
materials for effective pollution treatment. Herein, we report a facile approach
to synthesize carbonaceous nanofiber/NiAl layered double hydroxide (CNF/LDH)
nanocomposites for high-efficiency elimination of heavy metals from aqueous
solutions. The CNF/LDH nanocomposites were characterized by three-dimensional
architectures formed by the gradual self-assembly of flower-like LDH on CNF. The
nanocomposites exhibited excellent hydrophilicity and high structural stability
in aqueous solutions, guaranteeing the high availability of active sites in these
environments. High-efficiency elimination of heavy metal ions by the CNF/LDH
nanocomposites was demonstrated by the high uptake capacities of Cu(II) (219.6
mg/g) and Cr(VI) (341.2 mg/g). The sorption isotherms coincided with the
Freundlich model, most likely because of the presence of heterogeneous binding
sites. The dominant interaction mechanisms consisted of surface complexation and
electrostatic interaction, as verified by a combination of X-ray photoelectron
spectroscopy and Fourier-transform infrared spectroscopy analyses and density
functional theory calculations. The results presented herein confirm the
importance of CNF/LDH nanocomposites as emerging and promising materials for the
efficient removal of heavy metal ions and other environmental pollutants.
PMID- 29957542
TI - Air contamination by legacy and current-use pesticides in Brazilian mountains: An
overview of national regulations by monitoring pollutant presence in pristine
areas.
AB - In the last decades, research regarding the dynamics of pesticides has grown,
even in remote regions. Due to long-range atmospheric transport, environmental
persistence and toxicological potential of organochlorine pesticides (OCPs),
similar characteristics of current-use pesticides (CUPs) and their massive use in
Brazil, these contaminants have become a major concern for environmental and
human life. Thus, this study aimed to evaluate subgroups or individual chemicals
of OCPs and CUPs, which could have travelled over two Conservation Unit sites in
the Rio de Janeiro state. The study was carried out for 24 months, (2013-2015),
in Itatiaia National Park (INP) and in the Serra dos Orgaos National Park (SONP),
at ~2400 and ~2200 meters above sea level, respectively. The study was based on
atmospheric passive sampling (polyurethane foam disks). Target pesticides were
detected by means of gas chromatography device coupled with mass spectrometry (GC
MS). Significantly higher concentrations were measured in SONP when compared to
INP. However, in broad terms, the contamination profile was quite similar for
both national parks: The highest concentrations of endosulfan (INP - 1275 pg m-3
and SONP - 3202 pg m-3) were followed by cypermethrin (INP - 148 pg m-3 and SONP
881 pg m-3) and chlorpyrifos (INP - 67 pg m-3 and SONP - 270 pg m-3). In
agreement with previous studies, the atmospheric concentrations of legacy OCPs
showed background air levels. The decrease of endosulfan over the years was
highlighted with a parallel increase of chlorpyrifos, suggesting a collateral
effect of the national bias of permissive and massive use of agrochemicals. CUPs
seemed to behave like pseudo-persistent pollutants (pseudo-POPs). This is the
first report of atmospheric concentrations of pyrethroids in Brazilian mountain
regions, and possibly the first to investigate them in the air in South America
or in any mountain region in the world.
PMID- 29957543
TI - Nursing students' educational experience in regional Australia: Reflections on
acute events. A qualitative review of clinical incidents.
AB - Concerns have been expressed relating to healthcare professionals' ability to
manage deteriorating patients. Whilst on placement nursing students are exposed
to a range of behaviours and role models that may influence their future
practice. We aimed to identify events that impact upon the practice and
preparedness of Australian undergraduate nursing students in the management of
deteriorating patients. Methods included a Generic Qualitative Research design
reviewing 224 reflective reports on clinical events submitted by 92 final year
nursing students. Forty (40) patient deterioration events were identified and
subjected to detailed coding and thematic analysis. A range of events impacted
upon students' practice and preparation. Five themes and 15 subthemes were
identified including 'Communication' - the need for adequate handover and
documentation; 'Teamwork' - demonstrating the positive impact on patient
outcomes; 'Workload' - the negative effects of high staff/patient ratios;
'Clinical judgement/knowledge' - the need for adequate preparation of staff for
safe clinical settings; and negative outcomes relating to 'Attention Deficits'.
In conclusion Australian nursing students experience a range of practice
behaviours from exemplary leadership, to careless individual practices and a
'failure to rescue' deteriorating patients. Clinical experiences have a profound
influence on students with potential positive and negative effects on future
practice.
PMID- 29957544
TI - A fully automated system using transcription-mediated amplification for the
molecular diagnosis of hepatitis E virus in human blood and faeces.
AB - BACKGROUND AND OBJECTIVES: We evaluated the performance of the Procleix HEV RNA
assay implemented on the Panther automated platform for detecting HEV RNA. STUDY
DESIGN AND RESULTS: Analytical specificity was 100% and there was no cross
contamination, as assessed by assaying 122 plasma samples from HEV RNA-negative
blood donors. The limits of detection were determined by Probit analysis with the
WHO HEV standard (HEV subtype 3a) and subtype 3f and 3c reference strains. The
limit of detection was 24 [CI 95%: 19-33] IU/ml for subtype 3a, 34 [28-44] IU/ml
for subtype 3c and 53 [41-76] IU/ml for subtype 3f. Inclusivity was assessed by
testing 91 samples: HEV genotype 3 subtypes 3c (n = 29), 3e (n = 8), 3f (n = 50),
genotype 4 (n = 3), and genotype 1 (n = 1). All the samples tested positive.
Clinical performance was determined by testing prospectively 500 consecutive
plasma samples and 19 faecal samples with the Procleix assay and a reference
accredited quantitative RT-PCR assay. The assays were concordant for 492/500
plasma samples (98.4%) and 18/19 (94.7%) fecal samples. We also tested 92 IgM
positive/HEV RNA-negative samples with the reference assay. The IgM-positive
samples included 43 (46%) that tested negative with the reference RT-PCR assay
and positive with the Procleix HEV assay. CONCLUSIONS: The Procleix HEV assay
performed well and appears to be suitable for molecular diagnosis of HEV
infection, monitoring HEV infections, and facilitating epidemiological
investigations.
PMID- 29957545
TI - Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or
elvitegravir (EVG): Durability and virological response in a large Italian HIV
drug resistance network (ARCA).
AB - BACKGROUND: Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI)
with an increased genetic barrier to resistance with respect to raltegravir (RAL)
or elvitegravir (EVG). Few data are available on the durability of DTG-containing
regimens. OBJECTIVES: We aimed at investigating the duration of the DTG
containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated
with DTG virological response. STUDY DESIGN: From the Antiviral Response Cohort
Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects
who started DTG after receiving RAL or EVG. Factors associated with durability
and virological response were analysed by logistic regression. RESULTS: After a
median duration of 18.8 [0.4-76.2] months, 79/89 (88.8%) subjects were still on
DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1
RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less
frequent in patients who had experienced >=10 regimens (HR 0.11, p = 0.040). The
probability of having an HIV-1 RNA positive value at the last follow-up
significantly increased in patients with non-B HIV-1 subtype (HR 5.77, p < .001)
and significantly decreased in patients with CD4 nadir >200/MUL (HR 0.29, p =
0.038), with more than 10 previous regimens (HR 0.27, p = 0.040), and who
harbored virus with IN mutations (HR 0.12, p = 0.023) at DTG start. CONCLUSIONS:
After previous exposure to first-generation INIs, treatment with DTG showed long
durability and did not show virological rebound after virological suppression.
Subjects infected with a non-B HIV-1 subtype had a greater risk of having
detectable HIV-1 RNA at the last observation.
PMID- 29957547
TI - The relationship between internet addiction, social anxiety, impulsivity, self
esteem, and depression in a sample of Turkish undergraduate medical students.
AB - Internet addiction (IA) is currently becoming a serious mental health problem.
The aim of this study was to estimate the prevalence of IA among undergraduate
medical students and evaluate the relationship of IA with social anxiety,
impulsivity, self-esteem, and depression. The study included 392 undergraduate
medical students. Evaluations were made with the sociodemographic data form, the
Internet Addiction Test (IAT), the Liebowitz Social Anxiety Scale (LSAS), the
Barratt Impulsivity Scale-11 (BIS-11), the Rosenberg Self-Esteem Scale (RSES),
the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI). The IA
group had significantly higher scores on LSAS, BDI, BAI and lower scores on RSES
than the control group but the BIS-11 scores were similar among groups. IAT
severity was positively correlated with LSAS, BDI, and BAI and negatively with
RSES. No correlation was observed between IAT severity and BIS-11. In the
hierarchical linear regression analysis, the avoidance domain of social anxiety
was the strongest predictor of the severity of IA. The present study suggests
that undergraduate medical students with IA exhibit higher social anxiety, lower
self-esteem and are more depressed than those without IA, thus, indicating that
social anxiety, rather than impulsivity, seemed to play a prominent role in IA
psychopathology.
PMID- 29957546
TI - Development of a standardized real time PCR for Torque teno viruses (TTV) viral
load detection and quantification: A new tool for immune monitoring.
AB - BACKGROUND: Torque teno viruses (TTV) are small DNA viruses whose replication is
closely linked to immune status. A growing number of publications underlined the
potential of TTV viral load as an indicator of immunosuppression. OBJECTIVES: To
demonstrate the analytical performance of the first standardized RUO (Research
Use Only) assay to detect and quantify human TTV DNA in whole blood and plasma.
STUDY DESIGN: We established analytical performances for TTV load measurement in
various populations. The TTV kinetics were followed in kidney recipients. TTV
viral load was analyzed on whole blood samples from 42 kidney recipients follow
up, 53 kidney deceased donors and 31 healthy volunteers. RESULTS: The qPCR TTV
assay detects the most prevalent human TTV genotypes and does not cross react
with other viruses. Limit of detection was 2.2 log10 copies/mL in whole blood and
plasma, linearity and precision were demonstrated over the range 1.61 to 10.61
log10 copies/mL in whole blood. Prevalence of TTV DNA in blood differed
significantly among groups: 45% in healthy volunteers, 74% in donors and 83% in
kidney recipients. In kidney recipients, early TTV kinetics were comparable to
those previously observed with in-house assays in other transplant settings:
viral load increased from an average of 4.3 log10 to 7.9 log10 copies/mL within
the first 75 days post transplantation. CONCLUSION: This TTV assay showed high
analytical sensitivity, specificity, linearity and precision. It is a useful
standardized tool to further evaluate TTV load as a biomarker of immune status
that could improve individual treatment strategy.
PMID- 29957548
TI - Cognitive improvement in first-episode schizophrenia and healthy controls: A 6
year multi-assessment follow-up study.
AB - The development of individual cognitive domains over time is not yet fully
examined in first-episode schizophrenia (FES). This study's objective was to
explore the cognitive trajectories of FES-patients (n = 28) and compare them to a
pairwise matched healthy control group (n = 28, total n = 56). This study has a
multi-assessment design, and includes patient data from seven assessments over
six years. Healthy controls were assessed at baseline, after two years and after
six years. Cognition was assessed with the MATRICS Consensus Cognitive Battery.
Data were analyzed with linear multilevel models. FES-patients scored
significantly lower than the control group across all cognitive domains at
baseline. Over six years, improvements were seen in attention, verbal learning,
processing speed, reasoning/ problem solving, working memory and social
cognition. The overall trend points toward a similar cognitive change in both
groups. The patient group's improvement in reasoning/ problem solving was
significantly larger that the control group, but improvement in working memory
was smaller. Cognitive improvements were seen under and after the initial
psychosis episode and throughout the recovery process with 45.5% of the patients
fully recovered by 6-year follow-up. Cognitive improvements were seen in almost
every cognitive domain that is consistently impaired in FES.
PMID- 29957549
TI - The effect of sleep disturbances and internet addiction on suicidal ideation
among adolescents in the presence of depressive symptoms.
AB - Maladaptive use of internet and sleep problems is a significant health concern
among adolescents. We aimed to understand better how sleep problems are related
to suicidal ideation taking into account the presence of depression and internet
addiction. 631 adolescents aged between 12 and 18 randomly recruited from
different middle and high schools to complete self-report questionnaires
assessing sleep disturbances, addictive use of the internet, depressive symptoms,
and suicidal ideation. 22.9% of the sample reported on suicidal ideation during
the month before the study, 42% of the sample suffer from sleep disturbances,
30.2% reported on the addictive use of the internet, and 26.5% exhibited severe
symptoms of depression. Adolescents with suicidal ideation had higher rates of
sleep disturbances, addictive use of internet and depressive symptoms. A
confirmatory path analysis suggests that the effect of sleep disturbances on
suicidal ideation moderated by the impact of internet addiction and mediated by
the sleep effects on depressive symptoms. These results emphasize the importance
to address the above risk behaviors in prevention curriculums programs. Future
longitudinal studies are needed to determine the temporal order and to validate
causal pathways.
PMID- 29957550
TI - Assessment of the frequency criterion for the diagnosis of non-suicidal self
injury disorder in female adolescents with conduct disorder.
AB - Recent studies suggest a higher threshold number of self-injuries during the past
year than the one proposed in the DSM-5 criteria for non-suicidal self-injury
disorder (NSSID). Therefore, we aimed to test a validity of the frequency
criterion in girls with conduct disorder (CD) based on psychopathology and the
level of functioning. Mixture modelling analysis revealed that the frequency of
at least 8 self-harm behaviours in the previous year differentiated adolescents
with CD. Thus, we divided adolescents into three subgroups: group 1: at least 8
self-harm acts; group 2: 1-7 self-harm behaviours and group 3: those who did not
injure themselves during the last 12 months. Individuals from group 1 were
significantly younger and had earlier age of self-harm onset. There were
significant differences between groups 1 and 3 in terms of anxiety and depressive
symptoms, self-esteem, aggression and the global functioning level. The group 1
scored significantly higher on depressive symptoms compared to the group 2. The
group 2 scored significantly higher than the group 3 on the level of hostility.
Our results provide further evidence supporting the need for modification of the
NSSID frequency criterion.
PMID- 29957551
TI - Duration of untreated psychosis (DUP) and outcome of people with schizophrenia in
rural China: 14-year follow-up study.
AB - This study aims to examine the relationship between the duration of untreated
psychosis (DUP) and 14-year outcomes of schizophrenia in a Chinese rural area.
Participants with schizophrenia (n = 510) were identified in an epidemiological
investigation of 123 572 people aged 15 years and older in 1994 and followed up
in 2008 in Xinjin, Chengdu, China. Longer DUP (>6 months) was common in
participants (27.3%). In 1994, participants with DUP <= 6 months were more likely
to have a significantly lower rate of suicide attempts, shorter duration of
illness and higher rate of full remission compared with those with DUP > 6
months. No significant differences were found regarding the rates of survival,
suicide, death due to other causes and homelessness between individuals with
shorter and longer DUP in 2008. Nevertheless, longer DUP (>6 months) of
participants in 2008 was significantly associated with higher mean of PANSS total
negative and general mental scores, longer duration of illness and higher rate of
live alone in the logistic regression model. Earlier identification, treatment
and rehabilitation, and family intervention should be addressed when developing
mental health policies and delivering community mental health services.
PMID- 29957552
TI - Structured physical exercise and recovery from first episode psychosis in young
adults, the FitForLife study.
AB - Optimising autonomy is increasingly important in recovery from psychosis. To
date, physical exercise has shown promise in the treatment of severe, enduring
mental illnesses including psychosis - when used as an adjunct treatment. To
assess the association between physical exercise and autonomy in young adults, a
simple pre-post experimental design was utilised. Individuals aged 18-35 years,
treated at one of three specialist outpatient units for first-episode psychosis
in Stockholm, Sweden were invited to participate in a 12-week programme of
structured group exercise. Autonomy was measured using four questions from the
Camberwell Assessment of Needs questionnaire (physical health, social and close
relationship and daily tasks). Comparisons were made between: 'no attendance' and
'any attendance'. The latter group was bisected into higher and lower categories.
Ninety-four participants enrolled with a post-intervention response rate of 61%.
Significant reductions were seen in self-rated needs for care, though there was
no significant change in total scores or evidence of a dose response association.
The results suggest a plausible association between physical exercise and
autonomy which may represent the recovery process following the first episode of
psychosis. Further randomised control trials are needed to explore the potential
causality and robustness of this change.
PMID- 29957553
TI - Musical disability in children with autism spectrum disorder.
AB - Although enhanced musical ability is reported in individuals with autism spectrum
disorders (ASD), this observation may be uncommon, and reports of auditory
processing deficits suggest musical ability may be impaired. We hypothesized that
musical ability would be impaired in children with ASD, that the severity of
impairment would correlate with cognitive dysfunction, and with clinical features
of illness. We evaluated 26 children with ASD and 27 typically developing (TD)
children using the Montreal Battery of Evaluation of Amusia short version (MBEA
s) as well as cognitive tests and clinical evaluations of ASD symptomatology.
Mean scores on the MBEA-s were significantly lower in children with ASD. MBEA-s
scores did not correlate with cognitive test results in either ASD or TD
children, and did not correlate with symptom severity in ASD children. For the
ASD children only, the combination of hyperactivity/inattention and working
memory resulted in a significant contribution to the variance in the MBEA-s
score. The findings indicate that musical ability appears to be impaired in
children with ASD, and assessment of musical ability may complement cognitive
tests and measures of symptomatology in characterizing the shared neural
substrates for these dysfunctions in ASD.
PMID- 29957554
TI - Tempting fate: Chasing and maladaptive personality traits in gambling behavior.
AB - Chasing, or continuing to gamble in an attempt to recoup losses, is a salient
feature of problematic gambling. This study, which controlled for gambling
severity and alcohol consumption, investigated the association between chasing
and maladaptive personality trait domains among habitual gamblers. Participants
comprised 126 adult habitual gamblers (73% males) aged between 18 and 69 years.
They were administered the South Oaks Gambling Screen (SOGS), the Personality
Inventory for DSM-5-Brief Form (PID-5-BF), the Alcohol Use Disorders
Identification Test (AUDIT), and a computerized task developed to assess chasing
behavior. Participants were randomly assigned to two chasing conditions (Control
and Loss). Data were submitted to correlational analysis, univariate and mixed
model ANOVAs, logistic and linear regression analyses. Results showed that the
decision to chase was strongly associated with the PID-5-BF Disinhibition domain
scores, whereas chasing proneness was related to the Disinhibition, Detachment
and Psychoticism domains. Interestingly, chasers scored higher than nonchasers on
maladaptive personality dimensions, even after controlling for gender, age,
chasing condition, alcohol consumption, and gambling severity. Since these
findings support the idea that chasers and nonchasers are different subtypes of
gamblers, clinical interventions should take into account the additive role of
chasing in gambling disorder.
PMID- 29957555
TI - Exploring the pathophysiology of emotion-based impulsivity: The roles of the
sympathetic nervous system and hostile reactivity.
AB - The tendency to engage in impulsive behavior in the context of negative affect,
known as negative urgency, has emerged as a powerful transdiagnostic predictor of
behavioral dysregulation. Although general vulnerability to negative affect
(neuroticism) correlates with negative urgency, not all neurotic individuals
engage in urgent behavior. Given prior experimental evidence that sympathetic
nervous system (SNS) activation may promote emotion-related impulsivity, the
present study examines tonic SNS activity as a moderator of the link between
neuroticism and negative urgency. Participants (N = 194) completed measures of
neuroticism and negative urgency, as well as a stress task. They also underwent
assessment of tonic SNS activity (cardiac pre-ejection period). The link between
neuroticism and negative urgency was strengthened for individuals with higher
tonic SNS activity; however, this was not the case for behavioral performance on
the task. A similar pattern was demonstrated for hostile reactivity to the stress
task; increased hostile response partially explained the interaction between SNS
activation and neuroticism on negative urgency. These findings suggest a
potential facilitative role of the SNS in hostile reactivity and emotion-driven
impulsivity among more neurotic individuals.
PMID- 29957556
TI - A novel SCL-90-R six-item factor identifies subjects at risk of early adverse
outcomes in public mental health settings.
AB - To increase access to treatment, Italy made assessment at community mental health
centers (CMHCs) independent of medical referral, resulting in increased numbers
of patients to be triaged efficiently. To support this process, we evaluated SCL
90-R item-ratings to identify factors that best predicted adverse early outcomes
among persons seeking first-time CMHC care in a 24-month period in Rome. A
psychiatric nurse screened subjects with a brief interview and self-administered
SCL-90-R and psychiatrists provided CGI ratings and ICD-9 diagnosis. Of 832
screened subjects, 32 (3.85%) were hospitalized or attempted suicide within 90
days. Six SCL-90 items (15,41,55,57,78,88) scored much higher with than without
such adverse outcomes; their sum is proposed as a predictive measure ("SCL-6").
In binary multivariable logistic modeling, this factor, but not age, sex,
diagnosis, or other SCL-90-derived subscales strongly predicted adverse outcomes.
A ROC curve for SCL-6 reflected a strong separation between subjects with versus
without adverse outcomes (AUC = 0.76). This simple screening tool may support
timely identification of patients at risk of early adverse clinical outcome who
require especially close follow-up.
PMID- 29957557
TI - The impact of organized breast assessment on survival by stage for screened women
diagnosed with invasive breast cancer.
AB - PURPOSE: Since 1998, the Ontario Breast Screening Program (OBSP) has offered
organized assessment through Breast Assessment Centres (BAC). This study compares
survival between screened women diagnosed with breast cancer who have undergone
assessment through a BAC and usual care (UC). METHODS: A retrospective design
identified two concurrent cohorts of women aged 50 to 69 within the OBSP
diagnosed with screen-detected invasive breast cancer at a BAC (n = 2010) and UC
(n = 1844) between 2002 and 2010 and followed until 2016. Demographic and
assessment characteristics were obtained from the OBSP. Abstraction of medical
charts provided prognostic and treatment data. Death data were assessed from the
Registered Person's Database and the Ontario Registrar General All-Cause
Mortality File. Multivariable Cox proportional hazards models compared overall
survival by assessment type (BAC/UC), stratified by stage. RESULTS: There were
505 deaths during the study (BAC = 239; UC = 266). Among women with stage I
screen-detected breast cancer, those diagnosed through a BAC had 31% reduced risk
of all-cause mortality (HR = 0.69, 95% CI = 0.53-0.90) compared to UC. Diagnosis
within 7 weeks of an abnormal mammogram reduced the hazard of death from all
causes by 34% among all women with stage I breast cancers (HR = 0.66, 95% CI =
0.47-0.91), and was more likely in BAC (79.7%) than UC (66.9%). CONCLUSION: The
significant improvement in overall survival for women with stage I screen
detected invasive breast cancer assessed through BACs further supports the
recommendation that women with abnormal mammograms should be managed through
organized assessment.
PMID- 29957558
TI - Adaptive multinomial regression with overlapping groups for multi-class
classification of lung cancer.
AB - Multi-class classification has attracted much attention in cancer diagnosis and
treatment and many machine learning methods have emerged for addressing this
issue recently. However, class imbalance and gene selection problems occur in
classifying lung cancer data. In this paper, an adaptive multinomial regression
with a sparse overlapping group lasso penalty is proposed to perform
classification and grouped gene selection for lung cancer gene expression data.
An overlapped grouping strategy with biological interpretability is proposed,
which highlights the importance of gene groups from the minority classes. By
using the conditional mutual information, the gene significance within each group
is evaluated and the data-driven weights are constructed. Based on the grouping
strategy and constructed weights, a regularized adaptive multinomial regression
is presented and the solving algorithm is developed, which can not only select
the important gene groups for each class in performing multi-class
classification, but also adaptively select important genes within each group. The
experiment results show that the proposed method significantly outperforms the
other 6 methods on classification accuracy, and the selected genes are disease
causing genes for lung cancer.
PMID- 29957559
TI - A new feature for the classification of non-stationary signals based on the
direction of signal energy in the time-frequency domain.
AB - The detection of seizure activity in electroencephalogram (EEG) segments is very
important for the classification and localization of epileptic seizures. The
evolution of a seizure in an EEG usually appears as a train of non-uniformly
spaced spikes and/or as piecewise linear frequency modulated signals. If a
seizure is present, then the energy of the EEG is concentrated along the time
axis and the frequency axis in the time-frequency plane. However, in the absence
of a seizure, the energy of the EEG signal is uniformly distributed along all
directions in the time-frequency plane. Based on this observation, we propose a
new approach for the detection of a seizure. In this paper, we develop a new
feature that exploits the direction of the energy of the signal in the time
frequency domain to distinguish between seizures and non-seizures in an EEG. Our
experimental results indicate the superiority of the proposed approach over other
conventional time-frequency approaches; for example, the proposed feature set
achieves a classification accuracy of 98.25% by only using five features.
PMID- 29957560
TI - Communication skills of deaf and hard-of-hearing college students: Objective
measures and self-assessment.
AB - Objectively measured speech reception, speech production and expressive and
receptive sign skills were compared with the self-assessment ratings of those
skills in 96 college students with hearing loss. Participants with no aidable
hearing used cochlear implants (CIs) or nothing. Participants with aidable
hearing used either hearing aids (HAs) or nothing. Results revealed that
individuals using CIs had speech reception and production skills that were as
good as or better than students with more hearing who used HAs. Students using
CIs or HAs had better speech reception and production skills than those without
sensory aids. There was no difference in measured receptive sign skills across
groups, despite differences in age of sign acquisition. Students typically
provided accurate self-assessments of their communication skills with two notable
exceptions: CI users overestimated their speech skills and nonusers overestimated
their receptive sign skills. This study extends our knowledge regarding speech
reception, production, sign skills and the ability to self-assess those skills in
college students with hearing loss. Students who do not use sensory aids may be
at academic risk with regard to receiving input via speech or sign.
PMID- 29957561
TI - Economic evaluation of an expert examiner and different ultrasound models in the
diagnosis of ovarian cancer.
AB - The Risk of Malignancy Index (RMI) is commonly used to diagnose adnexal masses.
The aim of the present study was to determine the cost-effectiveness of the RMI
compared with subjective assessment (SA) by an expert and the following novel
ultrasound models: Cost-effectiveness and budget impact analyses were performed
from a societal perspective. A decision tree was constructed, and short-term
costs and effects were examined in women with adnexal masses. Sensitivity,
specificity and the costs of diagnostic strategies were incorporated. Incremental
cost-effectiveness ratios were expressed as costs/additional percentage of
correctly diagnosed patients. Probabilistic and deterministic sensitivity
analyses were performed. Effectiveness was highest for SA (90.7% [95% confidence
interval = 77.3-100]), with a cost saving of 5.0% (-?398 per patient [-?1403 to
549]) compared with the RMI. The costs of SR + SA were the lowest (?7180 [6072
8436]), resulting in a cost saving of 9.0% (-?709 per patient [-?1628 to 236])
compared with the RMI, with an effectiveness of 89.6% (75.8-100). SR + SA showed
the highest probability of being the most cost-effective when willingness-to-pay
was =200 ng/mL and <200
ng/mL, it was found that the frequency of neck compression was significantly
higher (P < 0.05) in the >=200 ng/mL group. The frequency of high Tg levels
(>=200 ng/mL) was increased among the cases in which death was caused by neck
compression or asphyxia. In a comparison of the median Tg values of right heart
blood, left heart blood, whole blood, and femoral venous blood, the median Tg
values of whole blood and right heart blood were shown to be about 10 times
higher than those of left heart blood and peripheral blood. It is said that high
postmortem blood Tg levels are caused by mechanical compression of the thyroid
gland. However, high Tg levels were detected in the half of the cases without
neck compression. Therefore, neck compression should be diagnosed carefully based
on autopsy findings and other information.
PMID- 29957589
TI - Erratum: "Diversity Outbred Mice Identify Population-Based Exposure Thresholds
and Genetic Factors that Influence Benzene-Induced Genotoxicity".
AB - [This corrects the article DOI: http://dx.doi.org/10.1289/ehp.1408202.].
PMID- 29957591
TI - Prospective Open-Label Study of 48-Week Subcutaneous Administration of
Mepolizumab in Japanese Patients with Severe Eosinophilic Asthma.
AB - BACKGROUND: Long-term efficacy and safety of mepolizumab in patients with severe
eosinophilic asthma has been evaluated by large-scale double-blinded placebo
control studies. However, a prospective open-label study of a long-term
subcutaneous administration of mepolizumab in Japanese patients with severe
eosinophilic asthma has not been reported. METHODS: This study was a prospective,
48-week, open-label trial in 32 Japanese patients with severe eosinophilic asthma
who received subcutaneous administration of 100 mg mepolizumab every 4 weeks.
Nine patients required daily use of oral corticosteroid despite the use of high
dose inhaled corticosteroid. Six patients with aspirin-exacerbated respiratory
disease were involved. RESULTS: No patients failed to be continued mepolizumab
administration for an entire trial period. All patients experienced no adverse
events during the treatment. None of the patients experienced asthma
exacerbations during an entire period. In fact, forced expiratory volume in one
second was increased significantly at 24 week (p < 0.01) and at 48 week (p <
0.05). Number of eosinophils in peripheral blood was reduced after the first
administration of mepolizumab in all patients, which was continued until 48 weeks
with mepolizumab administration. After the start of mepolizumab administration,
all of oral corticosteroid-dependent asthmatics successfully withdrew from the
use of corticosteroid without exacerbations in parallel with sustained reduction
in peripheral blood eosinophil count. Blood levels of thymus and activation
regulated chemokine and IgE were not changed with 48-week administration of
mepolizumab. CONCLUSIONS: This first prospective open-label pilot study in Japan
showed a long-term efficacy and safety of mepolizumab in patients with severe
eosinophilic asthma.
PMID- 29957590
TI - Spatial Modeling to Identify Sociodemographic Predictors of Hydraulic Fracturing
Wastewater Injection Wells in Ohio Census Block Groups.
AB - BACKGROUND: Hydraulically fractured wells produce 2-14 million liters of
wastewater, which may contain toxic and radioactive compounds. The wastewater is
predominantly disposed of using Class II injection wells. OBJECTIVE: Our
objective was to evaluate the relationship between sociodemographic
characteristics and injection well locations in Ohio. METHODS: Using state and
federal data sources, we classified Ohio census block groups by presence of
injection wells, number of hydraulically fractured wells, sociodemographic
factors (median household income, % white, population density, % >=high school
education, median age, voter turnout), and geographic information (land area,
water area, situated over shale). We modeled the odds of having at least one
injection well within a block group with respect to all covariates using three
multivariable models incorporating different spatial components to account for
similarities in neighboring block groups. RESULTS: In bivariate analyses, block
groups with injection wells (n=156) compared with those without (n=9,049) had
lower population density (71 vs. 2,210 people/mi2 or 27 vs. 854 people/km2),
larger median area (43.5 vs. 1.35 km2), higher median age (42.8 vs. 40.2 y), and
higher % white (98.1% vs. 92.1%). After adjustment using a spatial logistic
regression model, the odds of a block group containing an injection well were 16%
lower per $10,000 increase in median income [odds ratio(OR)=0.837; 95% credible
interval (CI): 0.719, 0.961] and 97% lower per 1,000 people/mi2 (or per 386
people/km2) increase (OR=0.030; 95% CI=0.008, 0.072). Block groups on shale and
those containing fewer hydraulically fractured wells were more likely to include
an injection well. Percentage white, median age, % >=high school education, and %
voter turnout were not significant predictors of injection well presence.
CONCLUSION: In Ohio, injection wells were inversely associated with block groups'
median incomes after adjusting for other sociodemographic and geographic
variables. Research is needed to determine whether residents in census blocks
with injection wells face increased risk of chemical exposures or adverse health
outcomes. https://doi.org/10.1289/EHP2663.
PMID- 29957592
TI - Up to 11 years of experience with the Melody valved stent in the right
ventricular outflow tract.
AB - AIMS: The aim of the study was to report up to 11 years of follow-up after Melody
valve implantation in the pulmonary position. METHODS AND RESULTS: This was a
single-institution non-randomised prospective observational study of all Melody
valves in the pulmonary position after discharge between 2006 and 2017 (n=188).
Mean age was 19.4 years (SD 13.2). The indication was stenosis (45%),
regurgitation (33%) and mixed (22%). Pre-stenting was performed in all except the
initial four patients. In stenotic lesions the peak gradient was 36 mmHg PIG (SD
12.0) after 11 years and in regurgitant lesions the maximal regurgitation was
2/4. Stent fractures were observed in 8.6%; only one grade III fracture required
redo PPVI. Surgical removal was carried out in seven (3.7%), redo PPVI in five
(2.7%). Endocarditis was diagnosed in 19 (10.2%) patients at a median of 2.3
years (0.7-8.8) after Melody implantation. Three were surgically removed early
because of persistent infection, 16 were sterilised; six required replacement
(three surgical, three redo PPVI). There were no valve- or procedure-related
deaths. CONCLUSIONS: The Melody valve shows a good preserved leaflet function up
to 11 years after implantation. The main reason for graft failure was
endocarditis, although in half of those patients no reintervention was needed.
After pre-stenting, stent fractures led very exceptionally to reintervention.
PMID- 29957593
TI - Randomized Evaluation of a Novel Biodegradable Polymer-Based Sirolimus-Eluting
Stent in ST-Segment Elevation Myocardial Infarction: The MASTER Study.
AB - AIMS: The MASTER study was designed to compare performance of a new biode
gradable polymer sirolimus-eluting stent (BP-SES) with a bare-metal stent (BMS)
in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND
RESULTS: The study was a prospective, randomized (3:1), controlled, single-blind
multi-center trial that enrolled 500 STEMI patients within 24h of symptom onset,
during 2013-2015. 375 were treated with BP-SES and 125 with BMS. 104 randomized
patients underwent angiographic follow-up at 6 months. The primary clinical
endpoint was target vessel failure (TVF), defined as cardiac death, MI not
clearly attributable to a non-target vessel, or clinically driven target vessel
revascu-larization (TVR) at 12 months. The primary angiographic endpoint was in
stent late lumen loss (LLL) at 6 months in the angiographic cohort. The major
secondary end-point for safety was a composite of all-cause death, recurrent MI,
unplanned infarct related artery revascularization, stroke, definite stent
thrombosis (ST) or major bleeding at 1 month. At 12 months, TVF occurred in 6.1%
of BP-SES and 14.4% of BMS patients (pnon-inferiority=0.0004), mainly driven by a
higher rate of repeat revascu-larization in BMS patients. The safety endpoint
occurred in 3.5% of BP-SES and 7.2% of BMS patients (p=0.127). In-stent LLL
demonstrated superiority (p=0.0125) of BP-SES (0.09+/-0.43mm) over BMS (0.79+/
0.67mm). CONCLUSIONS: The study showed clinical non-inferiority and angiographic
superiority of BP-SES versus a comparator BMS, suggesting that this novel DES may
be a potential treatment option in STEMI.
PMID- 29957594
TI - Peri-strut Low-intensity Area Assessed by Mid-term Follow-up Optical Coherence
Tomography may Predict Target Lesion Revascularization after Everolimus-Eluting
Stent Implantation.
AB - AIMS: Peri-strut low-intensity area (PLIA) assessed by optical coherence
tomography (OCT) has been reported as a potential marker of abnormal neointimal
healing. We aimed to evaluate the impact of PLIA on clinical events and its risk
factors. METHODS AND RESULTS: We enrolled 264 consecutive patients treated with
everolimus-eluting stent (EES) who underwent follow-up OCT 6-12 months after
stenting. Target lesion revascularisation (TLR) was evaluated at a mean 42.6
months after stenting. PLIA was identified in 102 patients; 162 patients did not
exhibit PLIA. Multivariate Cox hazard regression analysis indicated that the
presence of PLIA (PLIA+) was an independent risk factor for increased incidence
of TLR (HR: 4.608, P=0.003). In both early (<1 year) and late (>1 year) phases,
the incidence of TLR was significantly higher in the PLIA+ group (P<0.001 and
P<0.001, respectively). In the Cox hazard regression analysis, current smoking
and increased C-reactive protein level were independently associated with PLIA+
(hazard ratio [HR]: 1.737, P=0.009; HR: 2.435, P=0.008, respectively).
CONCLUSIONS: The presence of PLIA on mid-term OCT was associated with TLR after
EES implantation. Detailed stent assessment by mid-term OCT may help predict
stent failure in patients treated with EES.
PMID- 29957595
TI - Procedural and One-Year Outcomes of Patients Treated with Orbital and Rotational
Atherectomy with Mechanistic Insights from Optical Coherence Tomography.
AB - AIMS: We sought to evaluate procedural complications and 1-year clinical outcomes
for patients who underwent percutaneous coronary intervention (PCI) with orbital
(OA) and rotational atherectomy (RA). METHODS AND RESULTS: From a total of 13,467
patients who underwent PCI in our hospital between January 2013 and June 2016,
1149 consecutive patients were treated with atherectomy for moderately-severely
calcified lesions (184 with OA, 965 with RA). Procedural complications were
similarly observed in 2 groups except for higher dissection and perforation rates
with OA. Major adverse cardiovascular events (MACE) were defined as the composite
of death, myocardial infarction and target lesion revascularization.
Multivariable adjusted analysis showed that OA use was associated with comparable
adjusted 1-year MACE compared to RA use (hazard ratio 0.79 [95% confidence
interval 0.54-1.17], P=0.25). There were no significant differences in individual
MACE endpoints. Furthermore, we studied 67 patients with OCT images. OCT analysis
showed comparable tissue modification with a trend towards higher stent expansion
with OA vs. RA. CONCLUSIONS: OA use was associated with lower unadjusted but
similar adjusted 1-year MACE outcomes compared to RA with higher rates of
dissection and device-induced perforation.
PMID- 29957596
TI - Effect of Stenting on the Near-Infrared Spectroscopy-Derived Lipid Core Burden
Index of Carotid Artery Plaque.
AB - AIMS: Catheter-based intravascular near-infrared spectroscopy (NIRS) detects a
lipid signal from atherosclerotic plaque. The aim of this study was to describe
the effect of carotid artery stenting (CAS) on the lipid signal in a carotid
stenosis. METHODS AND RESULTS: We performed NIRS combined with intravascular
ultrasound (IVUS) during 120 CAS procedures. Minimal luminal area (MLA) and
plaque burden (PB) at the site of MLA were measured with IVUS and lipid core
burden index (LCBI), maximal LCBI in a 4-mm segment of the artery (LCBImax) and
LCBI in a 4-mm segment at the site of MLA (LCBImla) with NIRS-derived chemograms.
NIRS-IVUS imaging was performed at baseline, after stent implantation and after
balloon postdilatation. The most common lesion type was the fibrocalcific plaque
(76%). Lipid-rich plaque (LCBImax >=400) was present in 33% of carotid stenoses
and in 20% at the site of MLA. Median MLA increased significantly from baseline
to stent implantation (3.63 mm2 to 5.56 mm2, P<0.001) and to postdilatation (5.56
mm2 to 12.03 mm2, P<0.001). Median LCBI, LCBImax and LCBImla significantly
decreased from baseline to stent implantation: LCBI (60 to 8, P<0.001), LCBImax
(294 to 60, P<0.001) and LCBImla (124 to 0, P<0.001). Postdilatation of the stent
had no further significant effect on median LCBI (8 to 5, P=0.890), LCBImax (60
to 50, P=0.690) and LCBImla (0 to 0, P=0.438). CONCLUSIONS: Carotid artery
stenting significantly reduced the NIRS-derived lipid core burden index at the
stented segment.
PMID- 29957597
TI - Time-frequency analysis of the tip motion in liquids using the wavelet transform
in dynamic atomic force microscopy.
AB - The tip motion of the dynamic atomic force microscope in liquids shows complex
transient behaviors when using a low stiffness cantilever. The second flexural
mode of the cantilever is momentarily excited. Multiple impacts between the tip
and the sample might occur in one oscillation cycle. However, the commonly used
Fourier transform method cannot provide time-related information about these
transient features. To overcome this limitation, we apply the wavelet transform
to perform the time-frequency analysis of the tip motion in liquids. The
momentary excitation of the second mode and the phenomenon of multiple impacts
are clearly shown in the time-frequency plane of the wavelet scalogram. The
instantaneous frequencies and magnitudes of the second mode are extracted by the
wavelet ridge analysis, which can provide quantitative estimations of the tip
motion in the second mode. Moreover, the relations of the maximum instantaneous
magnitude (MIM) to the amplitude setpoint and the Young's modulus of the sample
surface are investigated. The results suggest that the MIM can be used to
characterize the nanomechanical property of the sample surface at high amplitude
setpoints.
PMID- 29957598
TI - Angle dependent molecular dynamics simulation of flux pinning in YBCO
superconductors with artificial pinning sites.
AB - A molecular dynamics (MD) simulation to simulate the vortices in superconductors
with artificial pinning sites is presented. The simulation reproduces the correct
anisotropic behavior in angular dependence of critical current. We also show that
the shape of the [Formula: see text] curve depends on the size of the pinning
sites and the change from p = 0.5 to [Formula: see text] is due to the breaking
of the vortex lattice to individually acting vortices. The results beautifully
correspond to experimental data. Furthermore, we found that the size and shape of
the c-axis peak observed with columnar pinning sites in [Formula: see text] also
depends on the size of the rods, larger pinning sites leading to wider peaks. The
results obtained from the MD-simulation are similar to those of the much more
computationally intensive Ginzburg-Landau simulations. Furthermore, the MD
simulations can provide insight to the vortex dynamics within the samples.
PMID- 29957599
TI - Field-induced canting of magnetic moments in GdCo5 at finite temperature: first
principles calculations and high-field measurements.
AB - We present calculations and experimental measurements of the temperature
dependent magnetization of a single crystal of GdCo5 in magnetic fields of order
60 T. At zero temperature the calculations, based on density-functional theory in
the disordered-local-moment picture, predict a field-induced transition from an
antiferromagnetic to a canted alignment of Gd and Co moments at 46.1 T. At higher
temperatures the calculations find this critical field to increase along with the
zero-field magnetization. The experimental measurements observe this transition
to occur between 44-48 T at 1.4 K. Up to temperatures of at least 100 K, the
experiments continue to observe the transition; however, at variance with the
calculations, no strong temperature dependence of the critical field is apparent.
We assign this difference to the inaccurate description of the zero-field
magnetization of the calculations at low temperatures, due to the use of
classical statistical mechanics. Correcting for this effect, we recover a
consistent description of the high-field magnetization of GdCo5 from theory and
experiment.
PMID- 29957600
TI - Transformation of molecular CO2-III in low-density carbon to extended CO2-V in
porous diamond at high pressures and temperatures.
AB - The ability to modify chemical bonding in dense heterogeneous solid mixtures by
applying high pressure and temperature opens new opportunities to develop a
greater number of novel materials with controlled structure, stability and
exceptional physical properties. Here, we present the transformation of highly
strained CO2-III (Cmca) filled in porous low-density carbons (LDC) to extended
CO2-V (I-42d) encapsulated in porous diamond (Fd-3m) at high pressures and
temperatures. The x-ray diffraction data indicates the density of porous diamond
is about 5%-8% lower than that of bulk diamond and undergoes the structural
distortion to monoclinic diamond (C2/m or M-carbon) upon pressure unloading. This
result, therefore, demonstrates a feasibility to use porous LDC as nm-scale
reactors to synthesize and store carbon dioxide and other high energy density
extended solids.
PMID- 29957601
TI - Photo-induced lattice contraction in layered materials.
AB - Structural and electronic changes induced by optical excitation is a promising
technique for functionalization of 2D crystals. Characterizing the effect of
excited electronic states on the in-plane covalent bonding network as well as the
relatively weaker out-of-plane dispersion interactions is necessary to tune photo
response in these highly anisotropic crystal structures. In-plane atom dynamics
was measured using pump-probe experiments and characterized using ab initio
simulations, but the effect of electronic excitation on weak out-of-plane van der
Waals bonds is less well-studied. We use non-adiabatic quantum molecular dynamics
to investigate atomic motion in photoexcited MoS2 bilayers. We observe a strong
athermal reduction in the lattice parameter along the out-of-plane direction
within 100 fs after electronic excitation, resulting from redistribution of
electrons to excited states that have lesser anti-bonding character between
layers. This non-trivial behavior of weakly bonded interactions during
photoexcitation could have potential applications for modulating properties in
materials systems containing non-covalent interactions like layered materials and
polymers.
PMID- 29957603
TI - Calciphylaxis in a patient without renal failure.
AB - Calciphylaxis is a rare disease that typically presents in patients with end
stage renal disease on dialysis or those who have received a renal transplant.
Nonuremic calciphylaxis leads to ischemia and subsequent necrosis of subcutaneous
tissue. Diseases associated with nonuremic calciphylaxis include primary
hyperparathyroidism, connective tissue disease, malignancy, and alcoholic liver
disease. Due to its high mortality, early identification and an aggressive
multidisciplinary treatment approach is necessary to improve patient outcomes.
PMID- 29957604
TI - Understanding posterior reversible encephalopathy syndrome.
AB - Posterior reversible encephalopathy syndrome is a characteristic clinical
radiographic syndrome with diverse and multifactorial causes. Symptoms include
headache, altered mental status, seizures, nausea and vomiting, and vision
abnormalities. The syndrome is treated by lowering BP, administering
anticonvulsant medications, correcting metabolic abnormalities, and removing
offending agents. Secondary complications include ischemia, hemorrhage, and
cerebral infarction.
PMID- 29957605
TI - Combined angiotensin receptor and neprilysin inhibition therapy for heart
failure.
AB - The FDA has approved sacubitril/valsartan, an angiotensin-receptor-neprilysin
inhibitor, for the treatment of chronic symptomatic heart failure (stage C) in
patients with a left ventricular ejection fraction of 35% or less. This article
discusses results from a major clinical trial, PARADIGM-HF, and the role of this
new drug in heart failure treatment.
PMID- 29957607
TI - The new Israeli PA.
AB - Israel launched its new physician assistant profession with its first class of
students, who were graduated in October 2017. The program is run by the Ministry
of Health's Training and Development Department. This first course was focused on
emergency medicine and the plan is to expand to anesthesiology and pathology in
the near future.
PMID- 29957608
TI - Malaria.
PMID- 29957606
TI - Effectiveness of NPs and PAs in managing diabetes and cardiovascular disease.
AB - BACKGROUND: The effectiveness of cardiovascular disease (CVD) and diabetes care
delivered by NPs and physician assistants (PAs), and resource use by these
providers has not been studied. METHODS: We performed regression analyses of
patients with diabetes or CVD with a primary care visit in 130 Veterans Affairs
(VA) facilities to assess the association between provider type and effectiveness
or resource use. RESULTS: The diabetes cohort consisted of 156,034 patients
assigned to NPs and 54,590 assigned to PAs. Glycemic and BP control, statin use,
number of primary or specialty care visits, lipid panels, and A1C results were
comparable between groups. The CVD cohort consisted of 185,694 patients assigned
to NPs and 66,217 assigned to PAs. BP control; use of beta-blockers, statins, or
antiplatelets; primary or specialty care visits; lipid panels; and number of
stress tests ordered were comparable between groups. CONCLUSION: Effectiveness of
care and resource use among patients in both groups were comparable.
PMID- 29957609
TI - Using drug monitoring programs to optimize pain management for elective surgery
patients.
AB - This article describes an innovative workflow that incorporates the prescription
drug monitoring program (PDMP) into a suggested workflow for managing pain in
elective surgery patients. Using the PDMP and working with the patient's pain
management provider, clinicians can make sure that patients on chronic opioid
therapy are identified before admission so that their care can be individualized,
a plan developed to manage postoperative pain, and the patient can be
transitioned seamlessly back to outpatient pain management.
PMID- 29957610
TI - What is causing this patient's vulvar pain?
PMID- 29957611
TI - The least of the concerns.
PMID- 29957612
TI - Stories in measuring what matters.
PMID- 29957613
TI - An overview of anal intraepithelial neoplasia.
AB - Anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma (ASCC) are
on the rise in the United States, especially among men who have sex with men, HIV
positive or other immunocompromised patients, and women with a history of
cervical, vaginal, or vulvar cancer. Strong evidence supports the human
papillomavirus as the causative factor in anal dysplasia; reducing the risk of
HPV infection can reduce rates of ASCC. High-risk patients should be screened for
AIN, but no universal screening guidelines exist, and more studies are needed to
develop a national protocol for screening and management of patients with AIN.
PMID- 29957615
TI - Therapeutic vaccination for HIV: hopes and challenges.
AB - PURPOSE OF REVIEW: This review summarizes the recent landscape of HIV therapeutic
vaccine research, emphasizing the results of randomized controlled trials that
included analytical treatment interruption (ATI) to assess efficacy. RECENT
FINDINGS: Therapeutic vaccines for HIV are designed to re-educate the host immune
response in HIV-infected individuals to better control viral replication in the
absence of antiretroviral therapy. No therapeutic vaccine has yet to induce long
term HIV remission following ATI in a randomized controlled trial. This is likely
because the vaccines have not elicited a broad enough immune response to suppress
the diverse escape variants that emerge during viral rebound, and have not been
used with effective agents to reduce the HIV reservoir. Recent studies in
nonhuman primates using combination approaches are showing significant successes,
with several candidates eliciting significant antiviral activity following ATI.
Future studies pairing these vaccines with effective reservoir reduction hold
great promise. SUMMARY: Therapeutic vaccines aim to modulate the immune system of
HIV-infected individuals to elicit sustained virologic control in the absence of
antiretroviral therapy. Therapeutic vaccines that elicit broad immune responses
have recently shown promise in randomized controlled trials and nonhuman primate
studies.
PMID- 29957616
TI - Sickle cell disease is associated with higher mortality among patients
hospitalized with ischemic bowel disease.
AB - BACKGROUND: Sickle cell disease (SCD) is the most common inheritable hematologic
disorder in the USA and is associated with ischemic organ diseases. SCD
associated ischemic bowel disease is increasing being recognized, and studies on
the hospitalization outcomes of such patients are limited. OBJECTIVE: This study
aimed to compare the inpatient outcomes of ischemic bowel disease among patients
with SCD compared with patients without SCD. MATERIALS AND METHODS: This is a
case-control study using data from the National Inpatient Sample Database (2007
2014). We analyzed and compared outcomes between cases (ischemic bowel disease
with SCD) and controls (ischemic bowel disease without SCD), matched in a 1 : 5
ratio. The primary outcome was in-hospital mortality, and the secondary outcomes
were healthcare resource utilization including mechanical ventilation,
hemodialysis, transfusion, length of stay, and hospital charges. RESULTS: Of the
194 262 patients admitted with ischemic bowel disease, 98 had a diagnosis of SCD
and were matched successfully to the controls. In multivariate analysis, patients
with SCD had twice the mortality odds of those without (adjusted odds ratio=2.06,
95% confidence intervals: 1.13-3.74). They were more likely to require mechanical
ventilation and blood transfusion, and to be discharged to secondary health
facilities [1.68 (1.02-2.76), 3.32 (2.15-5.12), and 1.84 (1.02-3.35)]. Patients
with SCD also had a higher frequency of pneumonia, acute respiratory failure, and
hemodialysis for acute renal failure. There was no significant difference in the
length of stay or the total hospital charge between the two groups. CONCLUSION:
In patients hospitalized with ischemic bowel disease, SCD is associated with
significantly increased mortality and healthcare burden.
PMID- 29957618
TI - Seeing-and Nursing-Our Power.
AB - By standing up for patients, we stand up for ourselves.
PMID- 29957617
TI - Percutaneous versus open reduction and fixation for Tillaux and triplane
fractures: a multicenter cohort comparison study.
AB - The goal of this study was to compare open reduction versus percutaneous fixation
of adolescent ankle fractures with regards to the incidence of growth
disturbance. We performed a retrospective cohort analysis of adolescent patients
with triplane or Tillaux fractures. There was an even distribution of triplane
fractures and mean initial displacement between cohorts. Analysis of follow-up
radiographs revealed no instances of growth disturbance in the percutaneous
fixation group and six in the open reduction group (P=0.29). Growth disturbance
does not pose a significant concern when selecting a surgical approach. Owing to
the rarity of these fractures this study was underpowered.
PMID- 29957619
TI - What RNs Can Do to Improve the Health of Their Communities.
AB - We can make a difference in the places we learn, pray, work, and live.
PMID- 29957620
TI - HIV and Nurse Safety in China.
PMID- 29957621
TI - Recognizing Lyme Disease.
PMID- 29957622
TI - Simulation in Nursing Education.
PMID- 29957623
TI - Joint Commission Issues Alert Addressing Violence Against Health Care Workers.
AB - Document includes steps institutions can take to protect and prepare staff.
PMID- 29957624
TI - Ireland Proposes Promising Model for Nurse Staffing.
AB - In pilot studies, the framework reduced adverse events and absenteeism.
PMID- 29957625
TI - NewsCAP: The American Heart Association issues corrections to 2018 stroke
guidelines.
PMID- 29957626
TI - The Impact of Legalization of Medical and Recreational Marijuana.
AB - Study looks at Colorado youth.
PMID- 29957627
TI - NewsCAP: Soldiers in the U.S. Army who deploy within six months of an earlier
deployment are at higher risk for suicide.
PMID- 29957628
TI - NewsCAP: Each year an estimated 600 to 1,600 newborns fall or are dropped while
in the hospital.
PMID- 29957629
TI - State News Roundup.
PMID- 29957630
TI - NewsCAP: Study finds that NPs, physicians, and physician assistants (PAs) in the
VA system provide comparable diabetes management.
PMID- 29957631
TI - NewsCAP: The WHO releases Consolidated Guideline on Sexual and Reproductive
Health and Rights of Women Living with HIV.
PMID- 29957632
TI - Can You Be Fired for Taking a Sick Day?
AB - Know your rights and responsibilities when it comes to sick time.
PMID- 29957635
TI - Reducing Fall Risk in Older Adults.
AB - : Evidence supports addressing medication management.
PMID- 29957636
TI - Promoting Drug Safety in Older Adults.
PMID- 29957637
TI - New HIV Drug Treats Patients Unresponsive to Other Therapies.
PMID- 29957638
TI - After the Biopsy.
PMID- 29957640
TI - 1.5 CE Test Hours: Breast Cancer Screening: A Review of Current Guidelines.
PMID- 29957639
TI - 1.5 CE Test Hours: Original Research: The Efficacy and Safety of an RN-Driven
Ketamine Protocol for Adjunctive Analgesia During Burn Wound Care.
PMID- 29957641
TI - Ethics Champion Programs.
AB - A promising practice to promote moral agency in health care settings.
PMID- 29957642
TI - The Nurse's Part in the Recognition of Cancer of the Breast.
AB - Editor's note: From its first issue in 1900 through to the present day, AJN has
unparalleled archives detailing nurses' work and lives over more than a century.
These articles not only chronicle nursing's growth as a profession within the
context of the events of the day, but they also reveal prevailing societal
attitudes about women, health care, and human rights. Today's nursing school
curricula rarely include nursing's history, but it's a history worth knowing. To
this end, From the AJN Archives highlights articles selected to fit today's
topics and times.This April 1915 article was written by surgeon Howard
Lilienthal, the fifth president of the American Association for Thoracic Surgery
and the sole author of the first English-language textbook on thoracic surgery.
Here he writes to enlist nurses in the early recognition of breast cancer in
order to "control this disease by the only means now known"-that is, early
diagnosis and immediate surgery. "Your knowledge will enable you to speak with
authority and you, almost as much as the surgeon who operates, may be concerned
in saving a useful life."Today, routine mammography can identify breast cancer
before it is symptomatic, but there is not yet consensus among key organizations
about when screening should begin or how often it should be done. In this issue,
Roberta Baron and colleagues review the breast cancer screening guidelines of the
American Cancer Society, the U.S. Preventive Services Task Force, and the
National Comprehensive Cancer Network to help nurses better interpret and use
these recommendations.
PMID- 29957643
TI - New Medical Residents and Patient Mortality-Does the 'Nurse Effect' Lessen the
'July Effect'?
AB - : Updated several times a week with posts by a wide variety of authors, AJN's
blog Off the Charts allows us to provide more timely-and often more personal
perspectives on professional, policy, and clinical issues. Best of the Blog will
be a regular column to draw the attention of AJN readers to posts we think
deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com.
PMID- 29957644
TI - Making It Stick: Developing and Testing the Difficult Intravenous Access (DIVA)
Tool.
AB - : : Background: Establishing peripheral IV access for infusions is one of the
most common invasive procedures performed in the hospital setting, but it isn't
always successful on the first attempt. Multiple attempts delay treatment and
cause stress in patients and nurses. The literature reports that venipuncture
skills are among the most challenging for novice nurses to master. OBJECTIVES:
The goal of this quality improvement (QI) initiative was to develop, validate,
and refine a simple evidence-based tool that novice nurses can use in the
clinical setting to better identify those patients with preexisting conditions or
anatomical variances that result in difficult IV access. METHODS: Novice nurses
employed in an urban medical center were enrolled in a vascular access education
program with didactic and skill-enhancement components. Based on evidence found
in the literature, the QI team developed and piloted a difficult intravenous
access (DIVA) tool tailored to the adult patient population served by this
institution. Following an initial trial, the tool was further refined and
retested with a larger group of novice nurses. In the first phase, there were 94
IV insertion attempts; in the second, there were 971 attempts, for a total of
1,065. The two samples were analyzed independently using descriptive statistics,
and Pearson product moment correlation coefficients were calculated to examine
the relationship between the DIVA tool and the various factors that could affect
the establishment of IV access. RESULTS: Analysis of the first sample showed
moderate positive correlations between DIVA tool scores and five variables: tough
skin (scars, tattoos, or both), vein not palpable with tourniquet, vein not
visible with tourniquet, IV drug use, and chronic renal failure. Analysis of the
second sample showed high positive correlations between DIVA tool scores and the
two vein visibility variables; moderate positive correlations between DIVA tool
scores and chronic renal failure, altered fluid status, diabetes, IV drug use,
tough skin (scars, tattoos, or both), and only one arm available; and low
positive correlations between DIVA tool scores and frail and/or elderly skin and
chemotherapy. Analysis of the degree of correlation between DIVA tool scores and
the total number of IV insertion attempts per patient showed a moderate
correlation (r = 0.32). All correlations were significant at P < 0.01. Eighty
percent of the novice nurses who used the pilot tool and 84% who used the
modified tool rated it as a good indicator of the degree of difficulty of IV
access. CONCLUSIONS: The DIVA tool gave novice nurses a reliable indication of
the probable difficulty of an IV insertion and resulted in a change in the IV
policy standard at the institution, which now limits the number of peripheral IV
insertion attempts to two per nurse and four per patient, bringing current policy
into alignment with the 2016 Infusion Therapy Standards of Practice. Use of the
revised and validated DIVA tool has the potential to enhance patient comfort and
satisfaction and effect significant change in nursing practice.
PMID- 29957645
TI - Antibiotic Treatment for Clostridium difficile Infection in Adults.
AB - Editor's note: This is a summary of a nursing care-related systematic review from
the Cochrane Library. For more information, see http://nursingcare.cochrane.org.
PMID- 29957646
TI - Nursing Instructor Incivility Toward Students.
AB - : This article is one in a series on the roles of adjunct clinical faculty and
preceptors, who teach nursing students and new graduates to apply knowledge in
clinical settings. In this article, the author discusses instructor incivility
toward students, the possible reasons for this behavior, the outcomes of
instructor incivility, and suggestions for remediation.
PMID- 29957647
TI - Azithromycin Reduces Childhood Deaths in Africa.
PMID- 29957648
TI - Patients with Dementia have Better Surgical Outcomes in Hospitals with Better
Educated Nurses.
PMID- 29957649
TI - New Screening Tool Useful in Nurse Recruitment.
PMID- 29957650
TI - Nonprescription Treatments are an Option for Many Women with Postmenopausal
Vulvovaginal Symptoms.
PMID- 29957651
TI - We Remember Them, Too.
AB - A nurse's open letter to families who have lost a child.
PMID- 29957652
TI - Clinical Nurses' Perceptions of a Senior Capstone Dedicated Educational Unit.
AB - Clinical nurses' perceptions of a senior capstone dedicated educational unit
(DEU) model to transition to practice was evaluated in a pilot study. Nursing
students were placed in the traditional capstone and the DEU senior capstone unit
with clinical nurses. Staff nurses completed an online survey to compare and
contrast satisfaction and effectiveness of the models. The results of the study
revealed no perceived differences in the outcomes of a DEU experience as compared
to the traditional preceptor model. However, nursing management reported an
improved sense of leadership and teamwork on the unit with the DEU model.
PMID- 29957653
TI - Peace, Love, Field Day: An Innovative Approach to Cultivating Healthy Academic
Communities.
AB - The American Nurses Association declared 2017 the Year of the Healthy Nurse. In
an effort to promote a healthy academic environment, faculty and staff in
institutions of higher learning should serve as role models for healthy living
for their students. This article describes an innovative approach to cultivating
a healthy academic environment. Details about planning and implementation are
provided along with recommendations for future implementation.
PMID- 29957654
TI - Course Evaluation Summary: An Enlightening and Useful Documentation Tool for
Assessing Learner Outcomes and Developing Plans for Nursing Course Improvement.
AB - The Course Evaluation Summary (CES) is a data collection and analysis tool
designed to assess the extent to which course learning outcomes are met by
students within a course. Course assignments and assessments are linked to
outcomes, allowing for the comparison of target and actual outcomes and the
identification of strengths and areas of concern. The CES allows faculty to
develop an action plan for course improvement as needed and to document
implemented course changes and student concerns. Used every semester, the CES
provides a history of continuous course evaluation and course improvement.
PMID- 29957655
TI - Adaptive remodeling of renal Na+ and K+ transport during pregnancy.
AB - PURPOSE OF REVIEW: Renal ion transport undergoes dramatic changes during the
course of gestation. These adaptations are necessary to meet the dynamic
requirements of pregnancy and support fetal development. Pregnancy is
characterized by a high demand for both sodium and potassium. Recently there has
been work in the field profiling the modifications of the renal tubules in
pregnancy to meet these demands. The purpose of this review is to summarize these
findings. RECENT FINDINGS: The work to date suggests an important role for the
distal nephron in both the renal sodium and potassium reabsorption during
pregnancy. There is strong evidence that renal sodium reabsorption is mediated by
the epithelial sodium channel (ENaC). Whereas renal potassium reabsorption is
mediated by upregulation of potassium retaining transporters (HKA2) and
downregulation of potassium secreting channels (ROMK, BK). SUMMARY: Fetal growth
restriction and hypertensive disorders of pregnancy including preeclampsia are
marked by suboptimal maternal plasma volume expansion, which is determined by
renal electrolyte handling. Therefore, understanding the physiologic demand for
sodium and potassium in pregnancy and the adaptations required to support these
needs is necessary for the effective treatment of diseased states of pregnancy.
PMID- 29957656
TI - Nivolumab monotherapy or in combination with ipilimumab for metastatic melanoma:
systematic review and meta-analysis of randomized-controlled trials.
AB - Nivolumab, a completely human programmed death-1 inhibitor antibody, was first
approved by the Food and Drug Administration for patients with advanced malignant
melanoma resistant to other modalities of treatment. In 2015, it received
approval as the first line of treatment for malignant melanoma. We aimed to
synthesize evidence from published randomized-controlled trials on the safety and
efficacy of nivolumab, either alone or in combination with ipilimumab, in the
management of advanced unresectable melanoma. We searched the following
electronic databases: PubMed, Scopus, Web of Science, and Cochrane Central. The
records retrieved were screened for eligibility. Time-to-event data were pooled
as Hazard ratio using the generic inverse variance method and dichotomous data
were pooled as relative risk (RR) in a random-effects model. We used Review
Manager 5.3 software for windows. Four unique randomized-controlled trials (five
reports) with a total of 1910 patients (nivolumab group, n=1207 and control
group, n=703) were included. The overall effect estimate favored nivolumab plus
ipilimumab versus ipilimumab alone in terms of the objective response rate [RR:
3.58, 95% confidence interval (CI): 2.08-6.14], the complete response rate (RR:
5.93, 95% CI: 2.45-14.37), the partial response rate (RR: 2.80, 95% CI: 2.16
3.64), the stable disease rate (RR: 0.56, 95% CI: 0.41-0.76), and progression
free survival (hazard ratio: 0.67, 95% CI: 0.60-0.74). The pooled studies were
homogenous. Similar results were obtained for nivolumab monotherapy versus
chemotherapy comparison. Nivolumab alone or combined with ipilimumab
significantly improved the overall and complete response rates compared with
ipilimumab alone. In addition, nivolumab resulted in longer progression-free
survival with a comparable safety profile.
PMID- 29957657
TI - Colposcopy Evaluation at the Time of Loop Electrosurgical Excision Procedure May
Avoid Unnecessary Treatment.
AB - OBJECTIVE: The aim of the study was to assess the accuracy of colposcopy
evaluation at the time of the loop electrosurgical excision procedure (LEEP) to
identify women with a previous confirmatory diagnosis of squamous intraepithelial
lesion/cervical intraepithelial neoplasia (SIL/CIN) with low probability of
dysplasia in the LEEP specimen. MATERIALS AND METHODS: We prospectively recruited
a cohort of 162 women undergoing LEEP for histological high-grade SIL/CIN 2-3 or
low-grade SIL/CIN 1 with high-grade SIL cytology showing a fully visible
squamocolumnar junction in the colposcopy evaluation at the time of LEEP. At the
referral visit cervical cytology, human papillomavirus and genotype detection,
digital colposcopy, colposcopical lesion measurement, and 1 or more biopsies of
the transformation zone were obtained. The uterine cervix was colposcopically
evaluated intraoperatively. RESULTS: Thirty-four women (21.0%) had a normal
colposcopy evaluation at the time of the LEEP, whereas the remaining 128 women
showed abnormal findings. Absence of SIL/CIN in the LEEP specimen was confirmed
in 28 (82.3%) of the 34 women with a normal colposcopy at the time of LEEP group
and 8 (3.1%) of the 128 women showing abnormal colposcopy at the time of LEEP
group (p < .001). A normal colposcopic evaluation at the time of LEEP was
associated with an increase in the risk of absence of lesion in the cone specimen
compared with cases presenting an abnormal colposcopy (95% CI = 33.8-1,555.1, p <
.001). The colposcopy evaluation at the time of LEEP had a positive predictive
value of 82.3% (95% CI = 66.5-91.5) and a negative predictive value of 96.9% (95%
CI = 92.2-98.8) to predict low probability of SIL/CIN in the specimen.
CONCLUSIONS: Colposcopic evaluation at the time of LEEP seems to be accurate to
identify SIL/CIN postbiopsy regression; thus, its performance would be considered
at the time of the treatment.
PMID- 29957658
TI - Impact of Acetic Acid on HPV Testing Using Hybrid Capture 2.
AB - : As per the American Society for Colposcopy and Cervical Pathology guidelines,
human papillomavirus (HPV) testing is currently used as part of cervical cancer
screening and during colposcopy follow-up. The present project evaluated if the
application of acetic acid (AA) impacts HPV test results. METHODS: We conducted a
prospective nonrandomized interventional study. Participants referred for
colposcopy were eligible if immunocompetent, older than 18 years, and not
pregnant. Women in group A (controls) received 2 consecutive HPV tests without
application of AA. Women in group B had a first HPV sample collected before the
application of AA and a second sample collected 3 minutes after application of
AA. Samples were tested for HPV DNA with Hybrid Capture 2 (HC2) according to the
manufacturer's instructions. RESULTS: From October 17, 2012, to January 10, 2013,
approximately 101 women were recruited in 2 colposcopy clinics. In each group,
concordance was 98%, with only 1 participant having discordant results (testing
negative on the first sample and positive on the second sample). We found no
statistically significant difference in relative light units(RLUs) between groups
(median of difference, - 0.02 vs -0.05 RLU; p = .93). CONCLUSIONS: The results of
this study suggest that acetic acid at concentrations of 3% to 5% and sequential
cervical sampling do not modify the result of HPV testing by Hybrid Capture 2.
PMID- 29957659
TI - Attaining Gender Parity: Diversity 5.0 and 10 Best Practices for Global Health
Care Organizations.
AB - In view of the increasing global importance of women as consumers/patients,
employees, employers, and leaders, we discuss 10 best practices for the global
health care organizations to attain greater gender parity: (1) make diversity and
inclusion (D&I) an essential element of global strategy, (2), tailor global D&I
to fit local needs, (3) embed D&I throughout organizations, (4) multiply D&I
impact via external partnerships, (5) maximize the role of employee resource
groups, (6) maximize the role of diversity councils, (7) leverage D&I for
innovation, (8) leverage D&I for business development, (9) engage CEO, and (10)
make sharing of D&I best practices a meta best practice. These are practical
approaches that can be used in both overall strategic planning and in day-to-day
management of health care institutions. We examine this in the context of what we
call Gender Diversity 5.0, which will be an increasingly important part of
today's health care environment as the business imperative grows for diversity,
inclusion, and engagement at the patient, employee, and executive levels.
PMID- 29957660
TI - A Trial Study of Static Telepathology in Iran.
AB - Static telepathology is one of the telepathology methods, in which the captured
images of the slides are transmitted for consultation at a later time. This study
aimed to compare the diagnostic accuracy of the conventional pathology and static
telepathology systems. Eighty-two cases that had been selected randomly from 4
pathology centers in the city of Kerman were diagnosed by a pathologist, first
based on light microscopy and then after 2 months based on static images (2
images per case) captured by a Nikon 50i microscopic camera. The images were sent
to the pathologist via e-mail. The diagnostic accuracy of the telepathology
system was calculated. The light microscopic diagnoses were concordant with the
telepathologic diagnoses in 71 of 82 reviewed cases. Different diagnoses of 7
cases were due to the images captured from the inappropriate location of the
slides. The diagnostic accuracy of the telepathology system was 86.5%. The
results of this study showed that static telepathology is very accurate and can
be widely used in Iran. However, efficient implementation and use of
telepathology require paying attention to different issues such as educational,
legal, ethical, financial, and security and observance of the standards related
to this field.
PMID- 29957662
TI - Response of Cutaneous Squamous Cell Carcinoma to Treatment With Cetuximab.
PMID- 29957661
TI - Management of acute pancreatitis in the first 72 hours.
AB - PURPOSE OF REVIEW: Acute pancreatitis is a common condition that affects patients
with varying degrees of severity and may lead to significant morbidity and
mortality. The present article will review the current paradigm in acute
pancreatitis management within the first 72 h of diagnosis. RECENT FINDINGS:
Patients presenting with acute pancreatitis should be evaluated clinically for
signs and symptoms of organ failure in order to appropriately triage. Initial
management should focus on fluid resuscitation, with some data to support
Ringer's lactate over physiological saline. Routine use of prophylactic
antibiotics in acute pancreatitis is not recommended, nor is urgent endoscopic
retrograde cholangiopancreatography in the absence of concomitant acute
cholangitis. Early oral feeding should be encouraged, not avoided, and use of
parenteral nutrition is discouraged. Cholecystectomy during the same admission of
biliary pancreatitis should be performed in order to prevent future acute
pancreatitis episodes. Patients with acute pancreatitis secondary to alcohol
should receive alcohol counseling. Finally, there is ongoing interest in the
development of prognostic laboratory tests in acute pancreatitis and
pharmacological therapies to reduce the inflammation that occurs in acute
pancreatitis. SUMMARY: Acute pancreatitis is a common and heterogeneous condition
with the potential for significant morbidity. Best practices in acute
pancreatitis management focus on triage, hydration and enteral feeding.
PMID- 29957663
TI - Retrospective Evaluation of the Safety of Large Skin Flap, Large Skin Graft, and
Interpolation Flap Surgery in the Outpatient Setting.
AB - BACKGROUND: As the number of cutaneous surgeries continues to increase, it is
important to evaluate the safety of dermatologic surgery in the outpatient
setting. OBJECTIVE: The authors sought to determine postoperative bleeding,
infection, dehiscence, and necrosis rates in office-based dermatologic surgery
using large flap, large graft, and interpolation flap repairs. The authors
evaluated the relationship between these complications and surgical site, closure
type, repair size, antibiotic use, and antithrombotic use. METHODS: Eligible
patients were identified through searching the electronic medical records from
one Mohs micrographic surgeon at University Hospitals Medical Center. Patient
information, surgery characteristics, and complication information were
collected. Univariate and multivariate analyses were conducted to reveal
associations between each complication and closure type, repair size, repair
site, antithrombotic use, and antibiotic use. RESULTS: Three hundred and thirty
one reconstruction procedures after Mohs micrographic surgery and excision
qualified for the study. The rates of postoperative infection, hemorrhage,
hematoma, necrosis, and dehiscence were 5%, 0.3%, 2.4%, 3%, and 0.9%,
respectively. CONCLUSION: Complications were infrequent and non-life-threatening.
The authors' results indicate that dermatologic surgery using large flaps,
interpolation flaps, and large grafts is safe in the office setting.
PMID- 29957664
TI - Efficacy and Safety of a Low-Level Light Therapy for Androgenetic Alopecia: A 24
Week, Randomized, Double-Blind, Self-Comparison, Sham Device-Controlled Trial.
AB - BACKGROUND: Previous studies have reported the benefits of low-level/light laser
therapy (LLLT) for the promotion of hair regrowth. However, the effectiveness of
LLLT for the treatment of androgenetic alopecia (AGA) is still a topic of debate.
OBJECTIVE: To investigate the efficacy and safety of LLLT on hair regrowth in
patients with AGA. METHODS: This 24-week, randomized, double-blind, self
comparison, sham device-controlled trial enrolled 100 patients with AGA. All
participants were randomly assigned to receive the investigational LLLT on one
side of the head and sham light treatment on the contralateral side, 3 times
weekly for 30 minutes each, over a 24-week period. Global scalp photography,
phototrichogram assessment, the investigator's global assessment (IGA) of hair
regrowth, and the subject's assessment of the treatment satisfaction were used
for evaluation. RESULTS: After 24 weeks of treatment, the LLLT-treated scalp
exhibited significantly greater hair coverage than the sham light-treated side
(14.2% vs. 11.8%, p < .001). A significantly greater improvement from baseline in
hair thickness, hair count, hair coverage, and IGA were also observed in the LLLT
treated side than in the sham light-treated side at the 12- and 24-week visits.
No serious adverse events were observed. CONCLUSION: The use of LLLT might be an
effective, safe, well-tolerated treatment for AGA.
PMID- 29957665
TI - Sex Differences in Perioral Rhytides-Does Facial Hair Play a Role?
PMID- 29957666
TI - Population Pharmacokinetic Analysis of Gentamicin in Pediatric Extracorporeal
Membrane Oxygenation.
AB - BACKGROUND: Gentamicin pharmacokinetics may be altered in pediatric patients
undergoing extracorporeal membrane oxygenation (ECMO). Description of gentamicin
pharmacokinetics and relevant variables can improve dosing. METHODS: A
retrospective population pharmacokinetic study was designed, and pediatric
patients who received gentamicin while undergoing ECMO therapy over a period of 6
1/2 years were included. Data collection included the following: patient
demographics, serum creatinine, albumin, hematocrit, gentamicin dosing and serum
concentrations, urine output, and ECMO circuit parameters. Descriptive statistics
were used to characterize the patient population. Population pharmacokinetic
analysis was performed with NONMEM, and simulation was performed to identify
empiric doses to achieve therapeutic serum concentrations. RESULTS: A total of 37
patients met study criteria (75.7% male patients), with a median age of 0.17
[interquartile range (IQR) 0.12-0.82] years. Primary indications for ECMO
included the following: congenital diaphragmatic hernia (n = 17), persistent
pulmonary hypertension (n = 5), and septic shock (n = 4). Patients received a
total of 117 gentamicin doses [median 1.8 (IQR 1.4-2.9) mg/kg/dose] and had 125
serum concentrations measured at a median of 22.8 (IQR 15.8-25.5) hours after a
dose. Population pharmacokinetic analysis identified a 2-compartment model with
additive error as the best fit. Covariates included the following: allometrically
scaled fat-free mass on clearance, central and peripheral volume of distribution
(VDcentral and VDperipheral), and intercompartmental clearance; serum creatinine
on clearance; ultrafiltration rate on central volume of distribution. Simulation
identified dosage of 4-5 mg/kg/dose every 24 hours for neonates and infants as an
acceptable empiric dosing regimen. Children and adolescents had elevated trough
concentrations when dosed according to traditional dosing methods. CONCLUSIONS:
Fat-free mass should be used to dose gentamicin in pediatric ECMO patients. Serum
creatinine is a marker of gentamicin clearance and should be used to adjust
gentamicin dosing in pediatric ECMO patients.
PMID- 29957667
TI - Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update.
AB - BACKGROUND: Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment.
Since 1989, 18 new AEDs have been licensed for clinical use and there are now 27
licensed AEDs in total for the treatment of patients with epilepsy. Furthermore,
several AEDs are also used for the management of other medical conditions, for
example, pain and bipolar disorder. This has led to an increasingly widespread
application of therapeutic drug monitoring (TDM) of AEDs, making AEDs among the
most common medications for which TDM is performed. The aim of this review is to
provide an overview of the indications for AED TDM, to provide key information
for each individual AED in terms of the drug's prescribing indications, key
pharmacokinetic characteristics, associated drug-drug pharmacokinetic
interactions, and the value and the intricacies of TDM for each AED. The concept
of the reference range is discussed as well as practical issues such as choice of
sample types (total versus free concentrations in blood versus saliva) and sample
collection and processing. METHODS: The present review is based on published
articles and searches in PubMed and Google Scholar, last searched in March 2018,
in addition to references from relevant articles. RESULTS: In total, 171 relevant
references were identified and used to prepare this review. CONCLUSIONS: TDM
provides a pragmatic approach to epilepsy care, in that bespoke dose adjustments
are undertaken based on drug concentrations so as to optimize clinical outcome.
For the older first-generation AEDs (carbamazepine, ethosuximide, phenobarbital,
phenytoin, primidone, and valproic acid), much data have accumulated in this
regard. However, this is occurring increasingly for the new AEDs (brivaracetam,
eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine,
levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide,
stiripentol, sulthiame, tiagabine, topiramate, vigabatrin, and zonisamide).
PMID- 29957668
TI - Liquid Biopsies to Monitor Solid Organ Transplant Function: A Review of New
Biomarkers.
AB - Despite modern immunosuppressive therapy, allograft rejection remains a major
cause of solid organ transplant dysfunction. For clinical care, organ transplant
function is routinely monitored by measuring biomarkers that, depending on the
organ transplanted, include serum creatinine, N-terminal pro-hormone of brain
natriuretic peptide (NT-proBNP), and aspartate aminotransferase. All can be
measured easily in clinical chemistry laboratories. The main problem with these
biomarkers is that they have a low sensitivity for the detection of allograft
damage and are nonspecific for the detection of allograft rejection. To diagnose
rejection, histologic examination of grafted tissue is necessary, which requires
an invasive biopsy procedure. There is thus an unmet need in transplantation
medicine for biomarkers that are specific for rejection, identify graft injury at
an early stage, and may eventually overcome the need for a transplant biopsy.
Recently, tremendous progress in the field of biomarkers has been made. In this
narrative review, the potential of donor-derived cell-free DNA (ddcfDNA), cell
free nucleosomes, and extracellular vesicles to act as next-generation biomarkers
for solid organ transplant is discussed. Based on the fact that cell content is
released during rejection, these markers could serve as very specific biomarkers
for allograft injury and rejection. These markers have the potential to improve
rejection monitoring, evaluate the response to antirejection therapy, and may
decrease the need for invasive procedures.
PMID- 29957669
TI - Is an Intravenous Injection of Gadolinium Really Necessary for Intralabyrinthine
Schwannomas MR Examination?
AB - OBJECTIVES: Our aim was to confirm the usefulness of T2-weighted (T2W) gradient
echo sequence for detection and topographic diagnosis of intralabyrinthine
schwannomas (ILS) compared with T1W contrast-enhanced sequence as gold standard,
to evaluate the necessity of intravenous gadolinium injection for ILS follow-up
imaging. METHODS: Thirty patients with ILS were retrospectively enrolled and
compared to a control group of 30 patients with no inner ear pathology. All
patients underwent a T2W gradient-echo steady-state free precession (SSFP)
acquisition at 3T, which was visually analyzed by two radiologists and compared
to contrast-enhanced T1W sequence. A quantitative analysis was also performed,
with the measurement of the tumor and inner ear signal on T2W images and the
measurement of the tumor length in cochlear schwannomas. RESULTS: T2W FIESTA-C
sequence correctly diagnosed ILS with a sensitivity (Se) of 95% and a specificity
(Sp) of 100%, with matching results for their topographic evaluation (Se 92%, Sp
98%) compared with the gold-standard. The difference between the two sequences
was only 2.5%, with excellent interobserver agreement. The tumor signal on T2W
images was significantly lower than the normal bright signal of the normal inner
ear fluids (mean signal ratio = 0.42 vs 0.98). CONCLUSION: The positive and
topographic diagnostic accuracy of T2W FIESTA-C sequence was excellent compared
with the T1W contrast-enhanced sequence, even though the latter remains easier
and faster to analyze for an untrained radiologist. The performances of T2W
gradient-echo sequence at 3T make it a reasonable alternative strategy for
following ILS after they are diagnosed.
PMID- 29957670
TI - The Feasibility of Retrofacial Approach for Cochlear Implantation.
AB - HYPOTHESIS: The retrofacial approach is a feasible approach to the round window
niche and that the Round window-Sigmoid sinus line will help determine the
feasibility of retrofacial approach for cochlear implantation unless there is a
very high jugular bulb. BACKGROUND: When the round window cannot be visualized by
facial recess approach during cochlear implantation, other conservative
techniques can be used to improve visualization such as the retrofacial approach.
METHODS: Thirteen adult dry cadaveric temporal bones were studied. Computed
tomography (CT) scan was obtained on all temporal bones. An imaginary Round
window-Sigmoid sinus line was drawn on the axial images. We assessed whether this
line is anterior (including intersection) or posterior to the facial nerve (FN).
The following closest distances were measured on CT scans: 1) posterior
semicircular canal (PSC)-FN, 2) PSC-Stapedius muscle, 3) PSC-Jugular bulb, 4)
lateral semicircular canal (LSC)-Jugular bulb, 5) sigmoid sinus-FN. A canal wall
up mastoidectomy, facial recess, and retrofacial approach were performed in all
specimens. We have noted whether we need a standard or an extended mastoidectomy.
RESULTS: The Round window-Sigmoid sinus line was posterior to the FN in all
specimens. The retrofacial approach was feasible and the round window was
visualized in all specimens. Extended mastoidectomy was required in seven
specimens and the PSC-FN was <= 3 mm in five of them. CONCLUSION: Retrofacial
approach is feasible in cochlear implantation when the Round window-Sigmoid sinus
line is posterior to the FN and the jugular bulb is not obstructing the round
window.
PMID- 29957671
TI - Effects of Cartilage Overlay on the Tympanic Membrane: Lessons From a Temporal
Bone Study for Cartilage Tympanoplasty.
AB - HYPOTHESIS: Placing cartilage grafts on different tympanic membrane (TM)
locations will affect sound transfer function, and the effects will differ
according to the part of the TM modified. BACKGROUND: Cartilage tympanoplasty is
increasingly popular because of lower reperforation rates, and better long-term
stability. In this temporal bone study, we investigated the effect of placing
cartilage grafts over different parts of the normal TM on sound transmission.
METHODS: In 10 human fresh frozen temporal bones, umbo and stapes vibrations to
acoustic stimuli from 250 to 8000 Hz were measured at multiple points using a
scanning laser vibrometer. Four different cartilage arrangements were measured in
each temporal bone. 1) Overlay condition leaving an umbo rim of normal TM (Umbo
Rim). 2) Overlay condition leaving annular rim of normal TM (Annular Rim). 3)
Overlay condition leaving both rims of normal TM (Two Rims). 4) Overlay condition
leaving no normal TM exposed (No Rims). RESULTS: At low frequencies, there was a
statistically significant decrease in velocity from baseline for the No Rims
(umbo mean -4 dB; stapes -6 dB) and Umbo Rim (umbo -4 dB; stapes -3.7 dB)
conditions. All conditions showed significant decreases for middle frequencies
(umbo -4.0, -5.9, -7.4 and -6.3 dB; stapes -10.8, -6.6, -6.3 and -7.7 dB) and
high frequencies (umbo -13.2, -3.0, -3.1 and -5.5 dB; stapes -4.6, -2.4, -2.6 and
-3.5 dB). Results are in order for No Rims, Umbo Rim, Two Rims, and Annular Rim
conditions. CONCLUSION: In the low frequencies, it seems to matter where the
cartilage is placed, and in particular the annular rim of the TM seems to be
important for the low-frequency acoustic transfer function. In the higher
frequencies, all graft placements caused some drop at all frequencies. In all
frequencies, effects were modest by clinical standards.
PMID- 29957672
TI - Light Chain Amyloidosis Presenting as Bilateral External Auditory Canal
Obstructing Masses.
AB - : A morbidly-obese 57-year-old diabetic and hypertensive man with chronic kidney
disease, diastolic heart failure, and bilateral hearing loss was found to have
soft tissue masses/densities in the lateral aspect of both auditory canals on
local examination and on imaging. He underwent biopsies of both ear canal masses
and histologic examination revealed amyloid deposits in the dermis. These
deposits were confirmed as AL (amyloid light chain) kappa-type amyloid by laser
mass spectrometry. A systemic work-up showed plasma cell dyscrasia with 9% kappa
light chain restricted plasma cells in the bone marrow as well as amyloid
deposits on a kidney biopsy.Involvement of the external auditory canals is a rare
manifestation of systemic amyloidosis with only 13 cases reported so far, of
which four cases had bilateral external auditory canal involvement, associated
with multiple myeloma. Interpretation of small biopsies can be challenging
especially with early, scant amyloid deposits, but a sufficient biopsy to type
amyloid by immunohistochemistry or laser mass spectrometry is imperative for
further management. Early diagnosis and treatment of systemic light chain
amyloidosis translates to better patient outcomes, while delay in management
could lead to dismal prognosis.
PMID- 29957673
TI - Strategies for Prevention of Mother-to-Child Transmission Adopted in the "Real
World" Setting: Data From the Italian Register for HIV-1 Infection in Children.
AB - BACKGROUND: Strategies for prevention of HIV-1 mother-to-child transmission
(PMTCT) have been continuously optimized. However, cases of vertical transmission
continue to occur in high-income countries. OBJECTIVES: To investigate changes in
PMTCT strategies adopted by Italian clinicians over time and to evaluate risk
factors for transmission. METHODS: Data from mother-child pairs prospectively
collected by the Italian Register, born in Italy in 1996-2016, were analyzed.
Risk factors for MTCT were explored by logistic regression analyses. RESULTS: Six
thousand five hundred three children (348 infections) were included. In our
cohort, the proportion of children born to foreign mothers increased from 18.3%
(563/3078) in 1996%-2003% to 66.2% (559/857) in 2011-2016 (P < 0.0001).
Combination neonatal prophylaxis use significantly (P < 0.0001) increased over
time, reaching 6.3% (56/857) after 2010, and it was largely (4.2%) adopted in
early preterm infants. The proportion of vaginal deliveries in women with
undetectable viral load (VL) increased over time and was 9.9% (85/857) in 2011
2016; no infection occurred among them. In children followed up since birth MTCT,
rate was 3.5% (96/2783) in 1996-2003; 1.4% (36/2480) in 2004-2010; and 1.1%
(9/835) in 2011-2016. At a multivariate analysis, factors associated with MTCT
were vaginal delivery with detectable or missing VL or nonelective caesarean
delivery, prematurity, breastfeeding, lack of maternal or neonatal antiretroviral
therapy, detectable maternal VL, and age at first observation. Previously
described increased risk of offspring of immigrant women was not confirmed.
CONCLUSIONS: Risk of MTCT in Italy is ongoing, even in recent years, underling
the need for implementation of the current screening program in pregnancy. Large
combination neonatal prophylaxis use in preterm infants was observed, even if
data on safety and efficacy in prematures are poor.
PMID- 29957674
TI - Early and Highly Suppressive ART are Main Factors Associated with Low Viral
Reservoir in European Perinatally HIV Infected Children.
AB - BACKGROUND: Future strategies aiming to achieve HIV-1 remission are likely to
target individuals with small reservoir size. SETTING: We retrospectively
investigated factors associated with HIV-1 DNA levels in European, perinatally
HIV-infected children starting ART <6 months of age. METHODS: Total HIV-1 DNA was
measured from 51 long-term suppressed children 6.3 years (median) after initial
viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed
using linear regression. RESULTS: At ART initiation, children were aged median
[IQR] 2.3 [1.2,4.1] months, CD4% 37 [24,45] %, CD8% 28 [18,36] %, log10 plasma
viral load (VL) 5.4 [4.4,5.9] copies/ml. Time to viral suppression was 7.98
[4.6,19.3] months. Following suppression, 13 (25%) children had suboptimal
response [>=2 consecutive VL50-400 followed by VL<50] and/or experienced periods
of virological failure [>=2 consecutive VL>=400 followed by VL<50]. Median total
HIV-1 DNA was 43 [6,195] copies/10 PBMC.Younger age at therapy initiation was
associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month
older, p=0.0091), with a month increase in age at ART start being associated with
a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally
suppressed (AC 0.10 per 10% higher, p=0.0022) and absence of viral
failure/suboptimal response (AC 0.34 for those with fail/ suboptimal response,
p=0.0483) were associated with lower total HIV-1 DNA. CONCLUSION: Early ART
initiation and a higher proportion of time suppressed are linked with lower total
HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1 infected
children minimize the size of viral reservoir.This is an open-access article
distributed under the terms of the Creative Commons Attribution-Non Commercial
License 4.0 (CCBY-NC), where it is permissible to download, share, remix,
transform, and buildup the work provided it is properly cited. The work cannot be
used commercially without permission from the journal.
PMID- 29957675
TI - Cognitive Performance and Frailty in Older HIV-Positive Adults.
AB - OBJECTIVE: This study examined the relative contribution of cognitive status to
frailty among older individuals infected with HIV+. DESIGN: Participants included
122 HIV+ individuals [mean age = 57.5 (6.6)] with a median CD4 cell count of 546.
Undetectable viral load (<50 copies per mL) was observed in 94% of the sample.
The sample was defined as frail (n = 21) and nonfrail (n = 101) according to the
Fried phenotype criteria. Cognitive tests included measures of executive
function, motor/psychomotor, language, learning, and memory. Performances were
converted to standardized scores and averaged to calculate individual domain
scores and a global index of cognitive function. METHODS: Logistic and
hierarchical regressions were completed to separately determine the associations
between clinical, demographic, and cognitive variables with regards to frailty
status. RESULTS: Results of the logistic regressions revealed that lower
executive function, female sex, and higher symptoms of depression were associated
with frailty. The hierarchical analysis revealed no significant contribution of
executive function to frailty status after accounting for female sex and symptoms
of depression (Nagelkerke R = 0.15). CONCLUSIONS: These results emphasize the
importance of sex distribution and mental health in explanatory models of frailty
in HIV. Further, interventions targeting symptoms of depression may increase
resilience in older HIV+ individuals.
PMID- 29957676
TI - Longitudinal Follow-up of Patients With Tracheobronchomalacia After Undergoing
Tracheobronchoplasty: Computed Tomography Findings and Clinical Correlation.
AB - PURPOSE: The purpose of this study was to evaluate intermediate and long-term
changes in expiratory tracheal collapsibility by computed tomography (CT) in
patients with tracheobronchomalacia following surgical treatment with
tracheobronchoplasty and to correlate CT findings with clinical findings.
MATERIALS AND METHODS: Between 2003 and 2016, 18 patients with
tracheobronchomalacia underwent tracheobronchoplasty and were imaged
preoperatively and postoperatively at both intermediate and long-term intervals.
Imaging included end-inspiratory and dynamic expiratory phase scans. The cross
sectional area of the airway lumen was measured at 2 standard levels (1 cm above
the aortic arch and carina). These measurements were used to calculate %
collapsibility. Clinical findings recorded included a questionnaire on
symptomatology and a 6-minute walk test. RESULTS: Before surgery, expiratory
collapsibility of the upper trachea was 72%+/-25% (mean+/-SD) and that of the
lower trachea was 68%+/-22%. On intermediate follow-up (mean, 1.5 y),
collapsibility significantly decreased to 37%+/-21% at the upper trachea and
35%+/-19% at the lower trachea (P<0.001). On long-term follow-up (mean, 6 y),
collapsibility increased to 51%+/-20% at the upper trachea and 47%+/-17% at the
lower trachea and was significantly worse than on intermediate follow-up
(P=0.002). However, collapsibility on long-term follow-up remained significantly
lower than preoperative collapsibility (P=0.015). Clinical findings showed a
similar trend as quantitative CT measurements. CONCLUSION: Expiratory tracheal
collapsibility substantially decreases after tracheobronchoplasty on intermediate
follow-up. At long-term follow-up, tracheal collapsibility shows a modest
increase, but remains significantly lower than the preoperative baseline.
Quantitative measurements from dynamic CT have the potential to play an important
role as imaging biomarkers for assessing response to tracheobronchoplasty.
PMID- 29957677
TI - Bioelectrical impedance analysis in the assessment of sarcopenia.
AB - PURPOSE OF REVIEW: Bioelectrical impedance analysis (BIA) is an accepted
technique to estimate low muscle mass for sarcopenia diagnosis. However,
muscularity assessment from BIA relies on prediction equations, estimating
different compartments according to the calibration method. Low muscle mass can
be defined using different approaches. RECENT FINDINGS: There is a lack of
standardization on how low muscularity is defined in the context of sarcopenia.
Recent studies have shown discrepant results for the estimation of low muscle
mass when different prediction equations are used in the same BIA device.
Different sarcopenia prevalence rates are observed if different definitions are
used to identify low muscle mass. Most of the studies using BIA for diagnosing
sarcopenia use the incorrect combination of specific population cut-off or a
different device from the original equation. SUMMARY: The lack of standardization
of BIA use for assessing muscularity results in a wide range of sarcopenia
prevalence rates among studies, even when conducted in the same population. As
BIA equations and cut-off values are population and device-specific, results
should be interpreted with caution when data from different devices are applied
in equations or using cut-off values from a different population.
PMID- 29957678
TI - Assessment of nutritional status: what does it mean?
PMID- 29957679
TI - The Psychiatry Morbidity and Mortality Incident Reporting Tool Increases
Psychiatrist Participation in Reporting Adverse Events.
AB - OBJECTIVES: Although the reporting of adverse events (AEs) is widely thought to
be a key first step to improving patient safety in hospital systems,
underreporting remains a common problem, particularly among physicians. We aimed
to increase the number of safety reports filed by psychiatrists in our hospital
system. METHODS: We piloted an online survey for psychiatry-specific AE
reporting, the Psychiatry Morbidity and Mortality Incident Reporting Tool (PMIRT)
for a 1-year period. An e-mail prompt containing a link to the survey was sent on
a weekly basis to all psychiatry department clinical staff. The primary outcome
was the total number of events reported by psychiatrists through PMIRT; secondary
outcomes were the total number of AEs and the number of serious harm events filed
by psychiatrists in our hospital's formal event reporting system before and after
implementation of the new protocol. RESULTS: Psychiatrists filed 65 reports in
PMIRT during the study period. The average number of AEs reported by
psychiatrists in the hospital's formal event reporting system significantly
increased after the intervention (P = 0.0251), and the average number of serious
harm events reported by psychiatrists increased nonsignificantly (P = 0.1394).
CONCLUSIONS: The combination of an increase in awareness of event reporting with
a psychiatry-specific AE reporting tool resulted in a significant improvement in
the number of reports by psychiatrists.
PMID- 29957680
TI - Encouraging Patients to Speak up About Problems in Cancer Care.
AB - OBJECTIVES: Many patients with cancer believe that something has gone wrong in
their care but are reluctant to speak up. This pilot study sought to evaluate the
impact of an intervention of active outreach to patients undergoing cancer
treatment, wherein patients were encouraged to speak up if they had concerns
about their care and to describe the types of concerns patients reported.
METHODS: Patients receiving cancer care at two sites were randomly assigned to an
intervention or control group. Intervention patients received a brochure
encouraging them to speak up about any concerns and an outreach telephone call
during which the interviewer explicitly asked about concerns. Participants in
both groups received baseline and follow-up questionnaires assessing their
perceptions of their care and whether anything had "gone wrong" and provided
ratings of health care providers' communication and responsiveness. Qualitative
content coding was used to categorize patient-reported concerns collected through
the baseline and follow-up questionnaires (both groups) and during telephone
outreach (intervention patients only). The primary outcome was the number of
patients reporting a concern about their care. Communication and responsiveness
ratings for intervention and control group patients were compared using t tests.
RESULTS: Of the 60 patients in the intervention group, 34 (56.7%) reported at
least one problem or concern, compared with 16 (29.1%) of the 55 patients in the
control group (P = 0.003). The telephone outreach in particular resulted in more
than half of those reached reporting a new concern (55.3%). We detected no impact
of the intervention on patients' ratings of communication or support for speaking
up. CONCLUSIONS: Patients in this study reported a variety of concerns in
response to active outreach, demonstrating that active outreach to patients can
provide healthcare teams and systems the opportunity to offer a real-time
response to the patient, identify where system improvements are needed, and
implement policies, procedures, or programs to prevent recurrences.
PMID- 29957681
TI - Comprehensive review of the extended middle cranial fossa approach.
AB - PURPOSE OF REVIEW: To review the current literature on the extended middle
cranial fossa (xMCF) approach and to provide a comprehensive description of the
relevant anatomy, indications, surgical technique, results, and complications.
RECENT FINDINGS: The xMCF approach expands the surgical exposure provided by the
sMCF approach, allowing access to the internal auditory canal, cerebellopontine
angle, prepontine cistern, anterior petrous apex, petrous carotid artery,
Meckel's cave, cavernous sinus, mid and upper clivus, and posterior lesions
approaching the jugular foramen. Preservation of serviceable hearing is possible
with success rates approximating 50% in vestibular schwannoma and meningioma
resection, and facial nerve outcome is excellent. SUMMARY: The xMCF is an
important approach for difficult to access lesions that additionally offers the
possibility of hearing preservation. This approach is also useful for vascular
lesions, auditory brainstem implantation, and lesions of mid-brainstem.
PMID- 29957682
TI - Congenital and acquired diseases related to stone formation.
AB - PURPOSE OF REVIEW: To summarize the latest findings of congenital and acquired
diseases related to stone formation and help understanding the multitude of
cofactors related to urolithiasis. RECENT FINDINGS: Urolithiasis is related to a
broad spectrum of congenital and acquired diseases and its management varies
according to the stone type, underlying disease or recurrence rate, but it also
changes according to recent findings and developments. As prevalence of
urolithiasis is constantly increasing, identification of high-risk stone formers
and early treatment is essential. Therefore, genetic evaluation like whole exome
sequencing becomes a pertinent part of further diagnostics. SUMMARY: Stone
formation is a very heterogeneous pathomechanism. This prompt us to look at every
patient individually particularly in high-risk patients, including stone and 24-h
urine analysis and additional diagnostic work-up based on stone type or
underlying disease.
PMID- 29957683
TI - Biological basis and early clinical results of immunotherapy for cisplatin
resistant germ cell cancer.
AB - PURPOSE OF REVIEW: Prognosis of patients with refractory or multiply relapsed
germ cell cancer (GCC) is dismal with a life expectancy of a few months only.
Thus, new targets and treatment options are urgently needed. Here, we review and
discuss the biological basis and first clinical results of immune-checkpoint
inhibition by targeting programed death 1 (PD-1) or its ligand (PD-L1) in
treatment-refractory GCCs. RECENT FINDINGS: There is a biological rationale to
evaluate immune-checkpoint inhibitors in refractory GCCs, as PD-L1 is often
expressed and refractory tumors often display mismatch repair deficiency or
microsatellite instability. However, the first published clinical phase II trial
evaluating pembrolizumab in unselected refractory nonseminoma patients was closed
early due to lacking clinical activity. On the contrary, single-case reports have
shown meaningful activity in some patients. SUMMARY: To date, targeted
treatments, including current immunotherapy approaches, have only shown very
limited activity. Although immune-checkpoint inhibition provides an effective
treatment option for various malignancies based on large randomized clinical
trials, data on the use of this immunotherapy in refractory GCC are scarce as
results of ongoing trials are pending.
PMID- 29957684
TI - Transitional Dynamics of Household Food Insecurity Impact Children's
Developmental Outcomes.
AB - OBJECTIVE: To determine how transitions into and out of varying degrees of food
insecurity impact children's academic competencies, executive functioning, and
social skills (i.e., self-control, interpersonal skills, externalizing behaviors,
and internalizing behaviors). METHOD: Data come from the nationally
representative kindergarten and first-grade waves of the Early Childhood
Longitudinal Study (2010-2011); 11,958 children attending 1289 schools are
included. Statistical analyses involve using a novel framework for measuring the
transitional dynamics and depth of food insecurity to predict children's
developmental outcomes using hierarchal linear models, which adjust for child-
and school-level confounders. RESULTS: Deepening food insecurity (DeepenFIS) was
detrimental to children's self-control (-0.208, p < 0.01), math (-0.153, p <
0.01), and working memory (-5.202, p < 0.05) scores. Remitting marginal food
insecurity was associated with negative effects on children's self-control (
0.082, p < 0.05) and interpersonal skills (-0.098, p < 0.01) but not on math or
working memory. Persisting marginal food insecurity (PersistMFIS) negatively
impacted children's self-control (-0.106, p < 0.05) and interpersonal skills (
0.115, p < 0.05). Emerging food insecurity (0.146, p < 0.01) and persisting food
insecurity (0.071, p < 0.05) had detrimental effects on children's externalizing
behaviors. CONCLUSION: Based on a novel food insecurity transitions framework and
examination of multiple developmental outcomes, this study highlights the
importance of examining both depth and transitional dynamics of food insecurity.
Findings indicate that DeepenFIS and PersistMFIS may have potentially the most
harmful effects on children's developmental outcomes. Clinically, findings
support the need for addressing food insecurity in early childhood, even if the
food insecurity challenges are marginal and just emerging.
PMID- 29957685
TI - Environmentally Friendly Measurement of Airborne Radon Using a Nonvolatile Liquid
Scintillation Absorbent.
AB - The practicality of using a liquid scintillation method with a nonvolatile liquid
scintillation absorbent for the measurement of airborne Rn (radon) in a residence
was examined. The relationship between the radioactivity absorbed by the liquid
scintillation absorbent and the radon concentration in the air was investigated
in a calibrated walk-in radon chamber. The equivalent radioactivity of radon was
calculated for Po radioactivity immediately after radioactive equilibrium was
attained using successive decay equations via alpha-particle spectrometry based
on the 1 h, indirect, selective measurement of the Po alpha-particle spectrum
generated after sampling radon. We confirmed that the amounts of radon absorbed
in the liquid scintillation absorbent were proportional to the radon
concentration in the air. The calibration curve that exhibited reliable
quantitative linearity from 500 to 8,000 Bq m in air was extrapolated to the
region between 0 and 500 Bq m using the least-squares method with data from 500
to 8,000 Bq m. The validity of the extrapolated curve at less than 500 Bq m was
confirmed by comparison of the measured radon concentrations in the room and
atmosphere with those determined using an existing ionization chamber. Variations
in the absorption of radon were observed due to changes in temperature and
humidity. The health and environmental safety of nonvolatile liquid scintillation
absorbent was also considered.
PMID- 29957686
TI - Effectiveness of an Imaging Plate System in Emergency 131I Thyroid Monitoring.
AB - The effect of temperature and shielding on the lower detection limit of a thyroid
I monitoring system was investigated in an anthropomorphic thyroid-neck phantom
fitted with an imaging plate. The phantom was loaded with an I aqueous solution
and monitored with the imaging plate for 10 min. After exposure, the plates were
incubated with or without the shield at 0, 10, 20, 25, 30, or 40 degrees C. The
latent image was read out at 0 min to 7 d after exposure. The thyroid equivalent
doses corresponding to the detection limit were calculated in six age categories,
using the inhalation equivalent dose coefficients recommended by the
International Commission on Radiological Protection. The detection limit was
distributed between 0.13 and 4.2 kBq, and depended on the age of subjects,
elapsed time, temperature, and shielding provision. The maximum detection limit
of 4.2 kBq was below the emergency screening level of 30 kBq in Japan. The
thyroid equivalent dose corresponding to the detection limit ranged from 0.17 to
46 mSv. From the maximum equivalent dose of 46 mSv, the effective dose was
estimated as 1.8 mSv, lower than the annual effective dose limit of 20 mSv for
radiation workers. At 2 d after exposure, the measured dose was below the annual
effective dose limit of 1 mSv for the public, regardless of age, temperature, and
shielding provision. The imaging plate system effectively monitors the I thyroid
levels in emergency situations.
PMID- 29957687
TI - Evidence for Adaptive Response in a Molecular Epidemiological Study of the
Inhabitants of a High Background-radiation Area of Yangjiang, China.
AB - Our previous studies have shown that cancer mortality in high background
radiation areas of China was lower than that in a control area, indicating the
possibility of an adaptive response in high background-radiation areas. Our aim
is to determine the effect of low-dose radiation on the level of DNA oxidative
damage, DNA damage repair, antioxidant capacity, and apoptosis in high background
radiation area and control area populations of Guangdong through a molecular
epidemiological study in order to identify adaptive response. Blood samples were
collected from male residents aged 50 to 59 y in a high background-radiation area
(Yangjiang) and a control area (Enping), and activities of superoxide dismutase,
glutathione, catalase, total antioxidant capacity, and expression of O6
methylguanine-DNA methyltransferase gene (MGMT), human 8-oxoguanine DNA N
glycosylase 1 gene (hOGG1), proapoptotic genes and antiapoptotic genes, oxidative
stress-related genes, as well as concentrations of 8-OHdG, TrxR, HSP27, and MT
COX2 were determined. The activities of antioxidative enzymes, relative mRNA
expression level of DNA repair genes, antiapoptotic genes, oxidative-stress
related genes HSPB1 and MT-COX2, and the concentration of antioxidant index TrxR
in the high background-radiation area population increased significantly compared
to the control population (p < 0.05). The relative mRNA expression level of
proapoptotic genes and the concentration of DNA oxidative damage index 8-OHdG
were significantly lower in the high background-radiation area compared to those
in the control area (p < 0.05). In conclusion, under long-term, natural, high
background, ionizing radiation, DNA damage-repair capacity and antioxidant
capacity of inhabitants in the high background-radiation area may be enhanced.
Additionally, it could induce up regulation of cell-survival gene expression and
down regulation of apoptotic gene expression. It might be speculated that
enhanced antioxidant and DNA repair capacity and inhibition of apoptosis might
play important roles in adaptive response of low-dose radiation in high
background-radiation areas.
PMID- 29957688
TI - Experiences of Population Monitoring Using Whole-Body Counters in Response to the
Fukushima Nuclear Accident.
AB - Whole-body counter measurements of residents of Fukushima Prefecture have been
extensively performed after the Fukushima Dai-ichi Nuclear Power Plant accident
in March 2011. These measurements have demonstrated that the levels of internal
contamination with radioactive cesium (Cs and Cs) in the residents are very low.
This article provides an overview of and lessons learned from these whole-body
counter measurements with emphasis on the technical problems encountered, and it
discusses the effective use of whole-body counters for assessing the internal
thyroid doses of individuals when direct measurements of I in the thyroid are
difficult or impossible to implement for the total affected population in a short
time after a nuclear reactor accident. The application of this dose
reconstruction method requires determining the intake ratio of I to cesium
isotopes at appropriate times and considers the short biological half-lives of
cesium isotopes, in particular for children.
PMID- 29957689
TI - Gamma and Beta Absorbed Dose Conversion Coefficients in the Range from 10 keV to
10 MeV for Accidental Exposures From Point Sources Placed in Clothing in
Proximity to the Body.
AB - Retrospective dose assessment following acute radiation exposures during
radiological incidents can be difficult and inaccurate due to the large
uncertainties associated with dose estimation. However, rapid and accurate dose
assessment is critical following an incident so that appropriate treatment can be
provided to the patient as early as possible. Incident dose assessment relies
heavily on biological dosimetry with corresponding large uncertainties for
inhomogeneous exposures, resulting from the estimates of whole-body doses, while
the assessment of absorbed doses to individual tissues might actually be more
appropriate for acute radiation exposures. Incident exposure scenarios for orphan
sources placed in a breast or back pants pocket were modeled using the
International Commission on Radiological Protection computational reference male
and female and the Monte Carlo N-particle code MCNP6 to compute absorbed dose
conversion coefficients for organs of interest for monoenergetic photon and beta
sources. The absorbed dose conversion coefficients are intended for use in
conjunction with source information to rapidly estimate absorbed doses to organs
of interest from radiological sources in one of the two pocket geometries.
Absorbed dose conversion coefficients also have been calculated specifically for
Co, Cs, and Ir. Those absorbed dose conversion coefficients were applied to data
from a radiological incident in Yanango, Peru, for comparison with published dose
assessments; the results agree within 20%. The conversion coefficients are
expected to provide an accurate tool for assessing doses for the modeled
geometries, provided uncertainties due to the exact source-body geometry and
exposure time are considered.
PMID- 29957690
TI - Modeling Tissue Heating From Exposure to Radiofrequency Energy and Relevance of
Tissue Heating to Exposure Limits: Heating Factor.
AB - This review/commentary addresses recent thermal and electromagnetic modeling
studies that use image-based anthropomorphic human models to establish the local
absorption of radiofrequency energy and the resulting increase in temperature in
the body. The frequency range of present interest is from 100 MHz through the
transition frequency (where the basic restrictions in exposure guidelines change
from specific absorption rate to incident power density, which occurs at 3-10 GHz
depending on the guideline). Several detailed thermal modeling studies are
reviewed to compare a recently introduced dosimetric quantity, the heating
factor, across different exposure conditions as related to the peak temperature
rise in tissue that would be permitted by limits for local body exposure. The
present review suggests that the heating factor is a robust quantity that is
useful for normalizing exposures across different simulation models. Limitations
include lack of information about the location in the body where peak absorption
and peak temperature increases occur in each exposure scenario, which are needed
for careful assessment of potential hazards. To the limited extent that
comparisons are possible, the thermal model (which is based on Pennes' bioheat
equation) agrees reasonably well with experimental data, notwithstanding the lack
of theoretical rigor of the model and uncertainties in the model parameters. In
particular, the blood flow parameter is both variable with physiological
condition and largely determines the steady state temperature rise. We suggest an
approach to define exposure limits above and below the transition frequency (the
frequency at which the basic restriction changes from specific absorption rate to
incident power density) to provide consistent levels of protection against
thermal hazards. More research is needed to better validate the model and to
improve thermal dosimetry in general. While modeling studies have considered the
effects of variation in thickness of tissue layers, the effects of normal
physiological variation in tissue blood flow have been relatively unexplored.
PMID- 29957691
TI - ERRATUM: Reply to Belcuore.
PMID- 29957694
TI - Cancer Rehabilitation: Read, Reflect, Act.
PMID- 29957695
TI - Next-Generation Cancer Rehabilitation: A Giant Step Forward for Patient Care.
AB - PURPOSE: The aim of the study was to review the current state of cancer
rehabilitation evidence and practice and delineate an agenda for building the
future of cancer rehabilitation care. FINDINGS: Despite the benefits of cancer
rehabilitation interventions and the unmet needs among patients with cancer, very
few patients receive these services. CONCLUSIONS: Interdisciplinary cancer
rehabilitation should be implemented from diagnosis forward. Building this care
involves coordinating efforts in four critical areas: innovating cancer
rehabilitation care delivery, expanding the team of providers, creating precision
medicine cancer rehabilitation, and demonstrating the value of cancer
rehabilitation to drive referrals and reimbursement. CLINICAL RELEVANCE: Creating
next-generation cancer rehabilitation care has the potential to improve the lives
of the growing population of cancer survivors.
PMID- 29957696
TI - Women's Rehabilitation Experiences Following Breast Cancer Surgery.
AB - BACKGROUND: Breast cancer survivors represent 23% of the 15.5 million cancer
survivors in the United States. Treatment-related morbidities such as adhesive
capsulitis and lymphedema impact functional ability and quality of life.
Postoperative exercises have been recommended for years. However, few studies
exist that describe the postoperative rehabilitation experience of breast cancer
survivors. PURPOSE: The purpose of the study was to examine the rehabilitation
experiences of women following breast cancer surgery. METHODOLOGY: The study used
a descriptive-correlational design. A convenience sample of 594 breast cancer
survivors completed and returned a mailed questionnaire. FINDINGS: Results
indicated that 61% reported that postoperative exercises were prescribed. Forty
eight percent reported performing the exercises as instructed. Performing
exercises as instructed was significantly associated with increased functional
ability (p < .0001). CONCLUSION: Breast cancer survivors who perform
postoperative rehabilitation exercises as instructed may improve functional
ability. CLINICAL IMPLICATION: Rehabilitation nurses can have an instrumental
role in the postoperative rehabilitation care of this population.
PMID- 29957698
TI - Collaboration Between Cancer Survivorship and Rehabilitation Programs With Head
and Neck Patients.
AB - PURPOSE: The purpose of this article is to present an example of collaboration
between a cancer survivorship and cancer rehabilitation program at an academic
affiliated hospital. FINDINGS: The article demonstrates the process of
identifying and treating the surgical and radiation effects experienced by a head
and neck cancer survivor. The specific roles of the advanced practice nurse and
the physical therapist in assessing, identifying and treating cancer treatment
effects such as lymphedema and orthopedic problems are highlighted. CONCLUSION:
The survivorship visit is an opportunity to identify treatment-related effects
amenable to rehabilitation and to refer head and neck cancer survivors to
physical therapy for further evaluation and treatment. CLINICAL IMPLICATION:
Collaboration between nurses and physical therapists engaged in survivorship care
can provide an effective and efficient pathway to improved functional outcomes
for cancer survivors.
PMID- 29957697
TI - Risk Factors for Falls in Adult Cancer Survivors: An Integrative Review.
AB - PURPOSE: The aim of the study was to identify risk factors for falls among cancer
survivors. DESIGN: Integrative literature review. METHODS: We searched PubMed,
Embase, CINAHL, Cochrane Central Register of Controlled Trials, and PEDro for
studies investigating fall risk in cancer. Reports of randomized controlled
trials, descriptive studies (quantitative and qualitative), and theoretical
papers meeting predetermined criteria were included. Quality ratings of included
studies were done, and data were extracted and compiled by two independent
reviewers. FINDINGS: Twenty-nine articles met inclusion criteria. Literature
quality was moderate (median quality score: 1.67 out of 3 possible points).
Heterogeneity of statistics and reporting methods precluded calculation of
summary effect sizes, but physical function, cognitive function, balance/gait,
and certain medication types appear to increase fall risk. CONCLUSIONS AND
CLINICAL RELEVANCE: Modifiable risk factors, such as those identified in this
review, represent tangible intervention targets for rehabilitation professionals
for decreasing the risk of falls among cancer survivors.
PMID- 29957699
TI - The Intersection of Rehabilitation and Palliative Care: Patients With Advanced
Cancer in the Inpatient Rehabilitation Setting.
AB - BACKGROUND: Patients diagnosed with advanced cancer often differ from the
traditional patient typically seen in the inpatient rehabilitation setting.
PURPOSE: To identify differences in care while highlighting the considerable
similarities between the complementary specialties of palliative care and
rehabilitation, and to provide rehabilitation clinicians with knowledge and
skills to enhance care for palliative care patients and their families.
METHODOLOGY: Narrative literature review describing common functional losses in
patients diagnosed with advanced cancer, followed by articulation of the
intersection of palliative care with traditional rehabilitation approaches and
goals. CONCLUSION: The evidence supports implementation of a distinct body of
skills and knowledge, referred to as "palliative rehabilitation," among inpatient
rehabilitation providers. CLINICAL IMPLICATIONS: Implementing palliative
rehabilitation skills can improve the quality of care within the inpatient
rehabilitation setting for patients with advanced cancer.
PMID- 29957700
TI - Diagnosis and Treatment of Edema and Lymphedema in the Cancer Patient.
AB - BACKGROUND: Lymphedema occurs commonly in cancer survivors. It is crucial to
properly assess cancer patients in order to distinguish lymphedema from general
edema and to initiate evidence based treatment. PURPOSE: To provide evidence
based recommendations for screening, evaluating, and treating lymphedema and to
establish the role of the nurse in the care of patients with lymphedema.
METHODOLOGY: Comprehensive overview with narrative literature review of evidence
based lymphedema diagnosis and treatment. FINDINGS: Cancer-related edema
represents numerous complex conditions. A variety of interventions are needed to
address prevention, early detection, patient education, and effective treatment.
CONCLUSION: Lymphedema treatment is complex and multimodal, and is provided by an
interdisciplinary team of properly trained professionals. Nurses play a major
role in evaluating, treating and educating patients on the signs and symptoms of
cancer-related edema and patient self-management. CLINICAL IMPLICATIONS: Evidence
based assessment and treatment should be initiated early to improve outcomes and
quality of life in patients with cancer-related lymphedema.
PMID- 29957704
TI - Individual and organizational psychosocial predictors of hospital doctors' work
related well-being: A multilevel and moderation perspective.
AB - BACKGROUND: The high prevalence of burnout and depression among doctors
highlights the need to understand the psychosocial antecedents to their work
related well-being. However, much of the existing research has been atheoretical,
operationalized a narrow measurement of well-being, and predominantly examined
such relationships at the individual level. PURPOSE: This study uses a multilevel
perspective to examine individual (i.e., job demands and resources) and
organizational-level psychosocial predictors of three measures of work-related
well-being: perceived stress, presenteeism, and work engagement. The job demands
resources theory underpins the postulated relationships. METHODOLOGY: The 2014
National Health Service Staff Survey was analyzed using multilevel modeling in
MPlus. The data set involved 14,066 hospital-based doctors grouped into 157
English hospital organizations (i.e., Trusts). RESULTS: Congruent with job
demands-resources theory, job demands (workplace aggression and insufficient work
resources) were stronger predictors of perceived stress and presenteeism than job
resources. Equally, job resources (job control and manager support) were
generally stronger predictors of work engagement than job demands. At the
organizational level, bed occupancy rates and number of emergency admissions
predicted work engagement. No hypothesized individual or multilevel interactions
were observed between any of the job demands and resources. PRACTICAL
IMPLICATIONS: The findings emphasize that a broader perspective of work-related
well-being among hospital doctors should be employed and the empirical value of
examining such relationships from a multilevel perspective. Successful health
intervention should target the appropriate antecedent pathway and recognize the
role of organizational-level factors when trying to manage hospital doctors' work
related well-being.
PMID- 29957705
TI - Innovation contest: Effect of perceived support for learning on participation.
AB - BACKGROUND: Frontline staff are well positioned to conceive improvement
opportunities based on first-hand knowledge of what works and does not work. The
innovation contest may be a relevant and useful vehicle to elicit staff ideas.
However, the success of the contest likely depends on perceived organizational
support for learning; when staff believe that support for learning-oriented
culture, practices, and leadership is low, they may be less willing or able to
share ideas. PURPOSE: We examined how staff perception of organizational support
for learning affected contest participation, which comprised ideation and
evaluation of submitted ideas. METHODOLOGY/APPROACH: The contest held in a
hospital cardiac center invited all clinicians and support staff (n ~ 1,400) to
participate. We used the 27-item Learning Organization Survey to measure staff
perception of learning-oriented environment, practices and processes, and
leadership. RESULTS: Seventy-two frontline staff submitted 138 ideas addressing
wide-ranging issues including patient experience, cost of care, workflow,
utilization, and access. Two hundred forty-five participated in evaluation.
Supportive learning environment predicted participation in ideation and idea
evaluation. Perceptions of insufficient experimentation with new ways of working
also predicted participation. CONCLUSION: The contest enabled frontline staff to
share input and assess input shared by other staff. Our findings indicate that
the contest may serve as a fruitful outlet through which frontline staff can
share and learn new ideas, especially for those who feel safe to speak up and
believe that new ideas are not tested frequently enough. PRACTICE IMPLICATIONS:
The contest's potential to decentralize innovation may be greater under stronger
learning orientation. A highly visible intervention, like the innovation contest,
has both benefits and risks. Our findings suggest benefits such as increased
engagement with work and community as well as risks such as discontent that could
arise if staff suggestions are not acted upon or if there is no desired change
after the contest.
PMID- 29957707
TI - Survival of Patients With Vancomycin-Resistant Enterococcus faecium Bacteremia
Treated With Conventional or High Doses of Daptomycin or Linezolid Is Associated
With the Rate of Bacterial Clearance.
AB - OBJECTIVES: Vancomycin-resistant enterococci are important pathogens for
healthcare-associated infections. Although linezolid is bacteriostatic and
daptomycin is rapidly bactericidal against vancomycin-resistant enterococci in
vitro, it is not clear whether they differ in their effect on bacterial clearance
in patients with vancomycin-resistant enterococci bloodstream infections. DESIGN:
Prospective observational study. SETTING: Two university hospitals and research
laboratory. PATIENTS: Patients with vancomycin-resistant enterococci bloodstream
infection proven by blood cultures were prospectively enrolled from January 2010
to July 2015. INTERVENTIONS: Sequential blood samples were collected. Real-time
quantitative polymerase chain reaction was used to monitor bacterial loads.
MEASUREMENTS AND MAIN RESULTS: One hundred eight patients with vancomycin
resistant enterococci bloodstream infection were enrolled. Quantitative
polymerase chain reaction assays were performed on 465 blood isolates. We found
this method to be closely correlated with colony-forming units and more sensitive
than culture. Sixty-three patients (58.3%) received "conventional dose"
daptomycin (6-9 mg/kg), 15 (13.9%) received high-dose daptomycin (>= 9 mg/kg),
and 30 (27.8%) were treated with linezolid (600 mg every 12 hr) as sole agents.
The initial mean bacterial load was 1.03 log10 copies/mL and unrelated to
survival. Survivors had a more rapid early bacterial clearance than nonsurvivors
(Delta log10 copies/mL/d; -0.16 vs 0.31; p = 0.02). Multivariable logistic
regression showed that a slower early bacterial clearance independently predicted
increased mortality (odds ratio, 3.21; 95% CI, 1.03-10.02; p = 0.045).
Conventional dose daptomycin was associated with a significantly slower rate of
bacterial clearance than high-dose daptomycin (Delta log10 copies/mL/d; -0.04 vs
0.41; p < 0.001) and linezolid (-0.04 vs -0.56; p = 0.043). CONCLUSIONS: We found
that survivors of vancomycin-resistant enterococci bloodstream infection had a
significantly more rapid early bacterial clearance by quantitative polymerase
chain reaction than nonsurvivors. High-dose daptomycin and linezolid were
associated with more rapid bacterial clearance than conventional dose daptomycin.
These results support recommendations that conventional dose daptomycin not be
used for the treatment of patients with vancomycin-resistant enterococci
bloodstream infection.
PMID- 29957706
TI - Association between pre-operative biological phenotypes and postoperative
pulmonary complications: An unbiased cluster analysis.
AB - BACKGROUND: Biological phenotypes have been identified within several
heterogeneous pulmonary diseases, with potential therapeutic consequences.
OBJECTIVE: To assess whether distinct biological phenotypes exist within surgical
patients, and whether development of postoperative pulmonary complications (PPCs)
and subsequent dependence of intra-operative positive end-expiratory pressure
(PEEP) differ between such phenotypes. SETTING: Operating rooms of six hospitals
in Europe and USA. DESIGN: Secondary analysis of the 'PROtective Ventilation with
HIgh or LOw PEEP' trial. PATIENTS: Adult patients scheduled for abdominal surgery
who are at risk of PPCs. INTERVENTIONS: Measurement of pre-operative
concentrations of seven plasma biomarkers associated with inflammation and lung
injury. MAIN OUTCOME MEASURES: We applied unbiased cluster analysis to identify
biological phenotypes. We then compared the proportion of patients developing
PPCs within each phenotype, and associations between intra-operative PEEP levels
and development of PPCs among phenotypes. RESULTS: In total, 242 patients were
included. Unbiased cluster analysis clustered the patients within two biological
phenotypes. Patients with phenotype 1 had lower plasma concentrations of TNF
alpha (3.8 [2.4 to 5.9] vs. 10.2 [8.0 to 12.1] pg ml; P < 0.001), IL-6 (2.3 [1.5
to 4.0] vs. 4.0 [2.9 to 6.5] pg ml; P < 0.001) and IL-8 (4.7 [3.1 to 8.1] vs. 8.1
[6.0 to 13.9] pg ml; P < 0.001). Phenotype 2 patients had the highest incidence
of PPC (69.8 vs. 34.2% in type 1; P < 0.001). There was no interaction between
phenotype and PEEP level for the development of PPCs (43.2% in high PEEP vs.
25.6% in low PEEP in phenotype 1, and 73.6% in high PEEP and 65.7% in low PEEP in
phenotype 2; P for interaction = 0.503). CONCLUSION: Patients at risk of PPCs and
undergoing open abdominal surgery can be clustered based on pre-operative plasma
biomarker concentrations. The two identified phenotypes have different incidences
of PPCs. Biologic phenotyping could be useful in future randomised controlled
trials of intra-operative ventilation. TRIAL REGISTRATION: The PROtective
Ventilation with HIgh or LOw PEEP trial, including the substudy from which data
were used for the present analysis, was registered at ClinicalTrials.gov
(NCT01441791).
PMID- 29957708
TI - Microcirculatory Impairment Is Associated With Multiple Organ Dysfunction
Following Traumatic Hemorrhagic Shock: The MICROSHOCK Study.
AB - OBJECTIVES: To assess the relationship between microcirculatory perfusion and
multiple organ dysfunction syndrome in patients following traumatic hemorrhagic
shock. DESIGN: Multicenter prospective longitudinal observational study. SETTING:
Three U.K. major trauma centers. PATIENTS: Fifty-eight intubated and ventilated
patients with traumatic hemorrhagic shock. INTERVENTIONS: Sublingual incident
dark field microscopy was performed within 12 hours of ICU admission (D0) and
repeated 24 and 48 hours later. Cardiac output was assessed using oesophageal
Doppler. Multiple organ dysfunction syndrome was defined as Serial Organ Failure
Assessment score greater than or equal to 6 at day 7 post injury. MEASUREMENTS
AND MAIN RESULTS: Data from 58 patients were analyzed. Patients had a mean age of
43 +/- 19 years, Injury Severity Score of 29 +/- 14, and initial lactate of 7.3
+/- 6.1 mmol/L and received 6 U (interquartile range, 4-11 U) of packed RBCs
during initial resuscitation. Compared with patients without multiple organ
dysfunction syndrome at day 7, patients with multiple organ dysfunction syndrome
had lower D0 perfused vessel density (11.2 +/- 1.8 and 8.6 +/- 1.8 mm/mm; p <
0.01) and microcirculatory flow index (2.8 [2.6-2.9] and 2.6 [2.2-2.8]; p < 0.01)
but similar cardiac index (2.5 [+/- 0.6] and 2.1 [+/- 0.7] L/min//m; p = 0.11).
Perfused vessel density demonstrated the best discrimination for predicting
subsequent multiple organ dysfunction syndrome (area under curve 0.87 [0.76
0.99]) compared with highest recorded lactate (area under curve 0.69 [0.53
0.84]), cardiac index (area under curve 0.66 [0.49-0.83]) and lowest recorded
systolic blood pressure (area under curve 0.54 [0.39-0.70]). CONCLUSIONS:
Microcirculatory hypoperfusion immediately following traumatic hemorrhagic shock
and resuscitation is associated with increased multiple organ dysfunction
syndrome. Microcirculatory variables are better prognostic indicators for the
development of multiple organ dysfunction syndrome than more traditional indices.
Microcirculatory perfusion is a potential endpoint of resuscitation following
traumatic hemorrhagic shock.
PMID- 29957709
TI - Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill Children
With Severe Sepsis: A Double-Blind, Placebo-Controlled Trial.
AB - OBJECTIVES: To evaluate the effect of probiotics on cytokines in children with
severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: ICU of a tertiary care teaching hospital in North India. PATIENTS:
Children 3 months to 12 years old with severe sepsis. INTERVENTIONS: Enrolled
children were randomized to probiotic (n = 50) and placebo (n = 50) groups.
Probiotic group received VSL#3 (Danisco-Dupont USA, Madison, WI) (Lactobacillus
paracasei, L. plantarum, L. acidophilus, L. delbrueckii, Bifidobacterium longum,
B. infantis, B. breve, Streptococcus salivarius; maltose and silicon dioxide),
and placebo group received maltose and silicon dioxide. Dose was 1 sachet twice
daily for 7 days. Blood was collected on days 1 and 7 for estimation of
interleukin-6, interleukin-12p70, interleukin-17, tumor necrosis factor-alpha,
interleukin-10, and transforming growth factor -beta1. "Primary outcome": Change
in cytokine levels in probiotic and placebo groups from day 1 to 7. "Secondary
outcomes": Sequential Organ Failure Assessment score, healthcare-associated
infections, ICU stay, and mortality. MEASUREMENTS AND MAIN RESULTS: On day 7,
probiotic group had significantly lower levels of proinflammatory cytokines
(interleukin-6 [80 vs 186 pg/mL, p = 0.001]; interleukin-12p70 [44 vs 79 pg/mL, p
= 0.001]; interleukin-17 [217 vs 293 pg/mL, p = 0.01]; and tumor necrosis factor
alpha [192 vs 348 pg/mL, p = 0.01]) and higher levels of antiinflammatory
cytokines (interleukin-10 [320 vs 240 pg/mL, p = 0.02] and transforming growth
factor-beta1 [311 vs 221 ng/mL, p = 0.01]) than placebo group. From day 1 to 7,
probiotic group showed significant decrease in proinflammatory cytokines
(interleukin-6 [196-80 pg/mL, p = 0.001]; interleukin-12p70 [71-44 pg/mL, p =
0.01]; interleukin-17 [258-217 pg/mL, p = 0.01]; and tumor necrosis factor-alpha
[347-192 pg/mL, p = 0.001]) and increase in antiinflammatory cytokines
(interleukin-10 [198-320 pg/mL, p = 0.001] and transforming growth factor-beta1
[216-311 ng/mL, p = 0.001]) as compared to placebo group. Sequential Organ
Failure Assessment score on day 7 was significantly less in probiotic group (1 vs
3). There was a nonsignificant trend toward lower incidence of healthcare
associated infections (14% vs 20%) and duration of ICU stay (6.5 vs 9 d) in
probiotic group. Mortality was similar in two groups. CONCLUSIONS: Probiotics
supplementation for 7 days resulted in significant decrease in proinflammatory
and increase in antiinflammatory cytokines in children with severe sepsis.
PMID- 29957710
TI - Use of a Novel, Electronic Health Record-Centered, Interprofessional ICU Rounding
Simulation to Understand Latent Safety Issues.
AB - OBJECTIVES: The electronic health record is a primary source of information for
all professional groups participating in ICU rounds. We previously demonstrated
that, individually, all professional groups involved in rounds have significant
blind spots in recognition of patient safety issues in the electronic health
record. However, it is unclear how team dynamics impacts identification and
verbalization of viewed data. Therefore, we created an ICU rounding simulation to
assess how the interprofessional team recognized and reported data and its impact
on decision-making. DESIGN: Each member of the ICU team reviewed a simulated ICU
chart in the electronic health record which contained embedded patient safety
issues. The team conducted simulated rounds according to the ICU's existing
rounding script and was assessed for recognition of safety issues. SETTING:
Academic medical center. SUBJECTS: ICU residents, nurses, and pharmacists.
INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Twenty-eight teams recognized
68.6% of safety issues with only 50% teams having the primary diagnosis in their
differential. Individually, interns, nurses, and pharmacists recognized 30.4%,
15.6%, and 19.6% of safety items, respectively. However, there was a negative
correlation between the intern's performance and the nurse's or the pharmacist's
performance within a given team. The wide variance in recognition of data
resulted in wide variance in orders. Overall, there were 21.8 orders requested
and 21.6 orders placed per case resulting in 3.6 order entry
inconsistencies/case. Between the two cases, there were 145 distinct orders place
with 43% being unique to a specific team and only 2% placed by all teams.
CONCLUSIONS: Although significant blind spots exist in the interprofessional
team's ability to recognize safety issues in the electronic health record, the
inclusion of other professional groups does serve as a partial safety net to
improve recognition. Electronic health record-based, ICU rounding simulations can
serve as a test-bed for innovations in ICU rounding structure and data
collection.
PMID- 29957711
TI - Cerebral Concussion Primes the Lungs for Subsequent Neutrophil-Mediated Injury.
AB - OBJECTIVES: Mild traumatic brain injury in the form of concussion is extremely
common, and the potential effects on pulmonary priming have been underestimated.
The aim of this study was to characterize the pulmonary response following mild
traumatic brain injury and assess the pulmonary susceptibility to lung injury
after a subsequent innocuous pulmonary insult. DESIGN: Experimental in vivo
study. SETTING: University research laboratory. SUBJECTS: Male CD1 mice.
INTERVENTIONS: We developed a model of concussive traumatic brain injury in mice
followed by pulmonary acid microaspiration. To assess the dependent role of
neutrophils in mediating pulmonary injury, we specifically depleted neutrophils.
MEASUREMENTS AND MAIN RESULTS: Lateral fluid percussion to the brain resulted in
neuronal damage and neutrophil infiltration as well as extensive pulmonary
interstitial neutrophil accumulation but no alveolar injury. Following subsequent
innocuous acid microaspiration, augmented alveolar neutrophil influx led to the
development of pulmonary hemorrhage that was reduced following neutrophil
depletion. CONCLUSIONS: This model shows for the first time that innocuous acid
microaspiration is sufficient to induce neutrophil-mediated lung injury following
mild concussion and that the extracranial effects of mild traumatic brain injury
have been underestimated.
PMID- 29957712
TI - Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients.
AB - OBJECTIVES: To investigate whether diabetes and glucose dysregulation
(hyperglycemia and/or hypoglycemia) are associated with ICU delirium. DESIGN:
Prospective cohort study. SETTING: Thirty-two-bed mixed intensive care in a
tertiary care center. PATIENTS: Critically ill patients admitted to the ICU with
transitions of mental status from awake and nondelirious to delirious or
remaining awake and nondelirious on the next day. Patients admitted because of a
neurologic illness were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: The study population consisted of 2,745 patients with 1,720 transitions
from awake and nondelirious to delirious and 11,421 nontransitions remaining
awake and nondelirious. Generalized mixed effects models with logit link function
were performed to study the association between diabetes mellitus, glucose
dysregulation, and delirium, adjusting for potential confounders. Diabetes was
not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73-1.18). In
all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI,
1.15-1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same
day (odds ratio adjusted, 1.65; 95% CI, 1.12-2.28) compared with normoglycemia
were associated with transition to delirium. Hypoglycemia was not associated with
transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73-3.71). In
patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted,
1.41; 95% CI, 1.16-1.68) and the occurrence of both hyperglycemia and
hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07-2.89) were
associated with transition to delirium. In patients with diabetes, glucose
dysregulation was not associated with ICU delirium. CONCLUSIONS: Diabetes
mellitus was not associated with the development of ICU delirium. For
hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted.
Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same
day were associated with ICU delirium but only in patients without diabetes. Our
study supports the institution of measures to prevent glucose dysregulation in
nondiabetic ICU patients and contributes to the understanding of the determinants
of delirium.
PMID- 29957713
TI - The Impact of Heart Rate Response During 48-Hour Rewarming Phase of Therapeutic
Hypothermia on Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Patients.
AB - OBJECTIVES: Bradycardia during therapeutic hypothermia has been reported to be a
predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests.
However, bradycardia occurrence rate may be influenced by the target body
temperature. During therapeutic hypothermia, as part of the normal physiologic
response, heart rate decreases in the cooling phase and increases during the
rewarming phase. We hypothesized that increased heart rate during the rewarming
phase is another predictor of favorable neurologic outcomes. To address this
hypothesis, the study aimed to examine the association between heart rate
response during the rewarming phase and neurologic outcomes in patients having
return of spontaneous circulation after out-of-hospital cardiac arrest. DESIGN: A
secondary analysis of the Japanese Population-based Utstein style study with
defibrillation and basic/advanced Life Support Education and implementation
Hypothermia registry, which was a multicenter prospective cohort study. SETTING:
Fourteen hospitals throughout Japan. PATIENTS: Patients suffering from out-of
hospital cardiac arrest who received therapeutic hypothermia after the return of
spontaneous circulation from 2005 to 2011. INTERVENTION: None. MEASUREMENTS AND
MAIN RESULTS: This study enrolled 452 out-of-hospital cardiac arrest patients, of
which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3%
had a good neurologic outcome. Heart rate response was calculated using heart
rate data recorded during therapeutic hypothermia in the abovementioned registry.
Heart rate response in the rewarming phase (heart rate response-rewarming) was
calculated as follows: (heart rate [post rewarming]-heart rate [pre
rewarming])/heart rate (pre rewarming) * 100. The primary outcome was an
unfavorable neurologic outcome at hospital discharge, that is, a Cerebral
Performance Category of 3-5. Multivariable logistic regression analysis was
performed to determine the association between heart rate response-rewarming and
unfavorable neurologic outcomes. Multivariable logistic regression analysis
showed that heart rate response-rewarming was independently associated with
unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78-0.96; p =
0.004). CONCLUSIONS: Increased heart rate in the approximately 48-hour rewarming
phase during therapeutic hypothermia was significantly associated with and was an
independent predictor of favorable neurologic outcomes during out-of-hospital
cardiac arrest.
PMID- 29957714
TI - Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A
Randomized Controlled Trial.
AB - OBJECTIVES: As the catabolic state induced by septic shock together with the
physical inactivity of patients lead to the rapid loss of muscle mass and
impaired function, the purpose of this study was to test whether an early
physical therapy during the onset of septic shock regulates catabolic signals and
preserves skeletal muscle mass. DESIGN: Randomized controlled trial. SETTING:
Tertiary mixed ICU. PATIENTS: Adult patients admitted for septic shock within the
first 72 hours. INTERVENTIONS: Patients were assigned randomly into two groups.
The control group benefited from manual mobilization once a day. The intervention
group had twice daily sessions of both manual mobilization and 30-minute
passive/active cycling therapy. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle
biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle
biopsies were analyzed for histology and molecular components of signaling
pathways regulating protein synthesis and degradation as well as inflammation
markers. Hemodynamic values and patient perception were collected during each
session. Twenty-one patients were included. Three died before the second muscle
biopsy. Ten patients in the control and eight in the intervention group were
analyzed. Markers of the catabolic ubiquitin-proteasome pathway, muscle atrophy F
box and muscle ring finger-1 messenger RNA, were reduced at day 7 only in the
intervention group, but without difference between groups (muscle atrophy F-box:
7.3% +/- 138.4% in control vs -56.4% +/- 37.4% in intervention group; p = 0.23
and muscle ring finger-1: -30.8% +/- 66.9% in control vs -62.7% +/- 45.5% in
intervention group; p = 0.15). Muscle fiber cross-sectional area (um) was
preserved by exercise (-25.8% +/- 21.6% in control vs 12.4% +/- 22.5% in
intervention group; p = 0.005). Molecular regulations suggest that the excessive
activation of autophagy due to septic shock was lower in the intervention group,
without being suppressed. Markers of anabolism and inflammation were not modified
by the intervention, which was well tolerated by the patients. CONCLUSIONS: Early
physical therapy during the first week of septic shock is safe and preserves
muscle fiber cross-sectional area.
PMID- 29957715
TI - Increasing Evidence-Based Interventions in Patients with Acute Infections in a
Resource-Limited Setting: A Before-and-After Feasibility Trial in Gitwe, Rwanda.
AB - OBJECTIVE: To evaluate whether a focused education program and implementation of
a treatment bundle increases the rate of early evidence-based interventions in
patients with acute infections. DESIGN: Single-center, prospective, before-and
after feasibility trial. SETTING: Emergency department of a sub-Saharan African
district hospital. PATIENTS: Patients > 28 days of life admitted to the study
hospital for an acute infection. INTERVENTIONS: The trial had three phases (each
of four months). Interventions took place during the second (educational program
followed by implementation of the treatment bundle) and third (provision of
resources to implement treatment bundle) phases. MEASUREMENTS AND MAIN RESULTS:
Demographic, clinical, and laboratory data were collected at study enrollment;
24, 48, and 72 hours after hospital admission; and at discharge. A total of 1,594
patients were enrolled (pre-intervention, n = 661; intervention I, n = 531;
intervention II, n = 402). The rate of early evidence-based interventions per
patient during Intervention Phase I was greater than during the pre-intervention
phase (74 +/- 17 vs. 79 +/- 15%, p < 0.001). No difference was detected when data
were compared between Intervention Phases I and II (79 +/- 15 vs. 80 +/- 15%, p =
0.58). No differences in the incidence of blood transfusion (pre-intervention,
6%; intervention I, 7%; intervention II, 7%) or severe adverse events in the
first 24 hours (allergic reactions: pre-intervention, 0.2%; intervention I, 0%;
intervention II, 0%; respiratory failure: pre-intervention, 2%; intervention I,
2%; intervention II, 2%; acute renal failure: pre-intervention, 2%; intervention
I, 2%; intervention II, 1%) were observed. CONCLUSIONS: Our results indicate that
a focused education program and implementation of an infection treatment bundle
in clinical practice increased the rate of early evidence-based interventions in
patients with acute infections (mostly malaria) admitted to a sub-Saharan African
district hospital. Provision of material resources did not further increase this
rate. While no safety issues were detected, this could be related to the very low
disease severity of the enrolled patient population (www.clinicaltrials.gov:
NCT02697513).
PMID- 29957716
TI - Surviving Sepsis Campaign: Research Priorities for Sepsis and Septic Shock.
AB - OBJECTIVE: To identify research priorities in the management, epidemiology,
outcome and underlying causes of sepsis and septic shock. DESIGN: A consensus
committee of 16 international experts representing the European Society of
Intensive Care Medicine and Society of Critical Care Medicine was convened at the
annual meetings of both societies. Subgroups had teleconference and electronic
based discussion. The entire committee iteratively developed the entire document
and recommendations. METHODS: Each committee member independently gave their top
five priorities for sepsis research. A total of 88 suggestions (Supplemental
Table 1, Supplemental Digital Content 2, http://links.lww.com/CCM/D636) were
grouped into categories by the committee co-chairs, leading to the formation of
seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy,
administration/epidemiology, scoring/identification, post-intensive care unit,
and basic/translational science. Each subgroup had teleconferences to go over
each priority followed by formal voting within each subgroup. The entire
committee also voted on top priorities across all subgroups except for
basic/translational science. RESULTS: The Surviving Sepsis Research Committee
provides 26 priorities for sepsis and septic shock. Of these, the top six
clinical priorities were identified and include the following questions: 1) can
targeted/personalized/precision medicine approaches determine which therapies
will work for which patients at which times?; 2) what are ideal endpoints for
volume resuscitation and how should volume resuscitation be titrated?; 3) should
rapid diagnostic tests be implemented in clinical practice?; 4) should empiric
antibiotic combination therapy be used in sepsis or septic shock?; 5) what are
the predictors of sepsis long-term morbidity and mortality?; and 6) what
information identifies organ dysfunction? CONCLUSIONS: While the Surviving Sepsis
Campaign guidelines give multiple recommendations on the treatment of sepsis,
significant knowledge gaps remain, both in bedside issues directly applicable to
clinicians, as well as understanding the fundamental mechanisms underlying the
development and progression of sepsis. The priorities identified represent a
roadmap for research in sepsis and septic shock.
PMID- 29957717
TI - Peer Support in Critical Care: A Systematic Review.
AB - OBJECTIVES: Identifying solutions to improve recovery after critical illness is a
pressing problem. We systematically evaluated studies of peer support as a
potential intervention to improve recovery in critical care populations and
synthesized elements important to peer support model design. DATA SOURCES: A
systematic search of Medical Literature Analysis and Retrieval System Online,
Cumulative Index to Nursing and Allied Health Literature, PsychINFO, and Excertpa
Medica Database was undertaken May 2017. Prospective Register of Systematic
Reviews identification number: CRD42017070174. STUDY SELECTION: Two independent
reviewers assessed titles and abstracts against study eligibility criteria.
Studies were included where 1) patients and families had experienced critical
illness and 2) patients and families had participated in a peer support
intervention. Discrepancies were resolved by consensus and a third independent
reviewer adjudicated as necessary. DATA EXTRACTION: Two independent reviewers
assessed study quality with the Newcastle-Ottawa Scale and the Cochrane Risk of
Bias Tool, and data were synthesized according to the Preferred Reporting Items
for Systematic Reviews guidelines and interventions summarized using the Template
for Intervention Description and Replication Checklist. DATA SYNTHESIS: Two
thousand nine-hundred thirty-two studies were screened. Eight were included,
comprising 192 family members and 92 patients including adults (with cardiac
surgery, acute myocardial infarction, trauma), pediatrics, and neonates. The most
common peer support model of the eight studies was an in-person, facilitated
group for families that occurred during the patients' ICU admission. Peer support
reduced psychologic morbidity and improved social support and self-efficacy in
two studies; in both cases, peer support was via an individual peer-to-peer
model. In the remaining studies, it was difficult to determine the outcomes of
peer support as the reporting and quality of studies was low. CONCLUSIONS: Peer
support appeared to reduce psychologic morbidity and increase social support. The
evidence for peer support in critically ill populations is limited. There is a
need for well-designed and rigorously reported research into this complex
intervention.
PMID- 29957718
TI - Anatomy and neural remodeling of the renal sympathetic nerve in a canine model
and patients with hypertension.
AB - BACKGROUND: The role of renal sympathetic nerve (RSN) in hypertension should be
better understood. We aimed to three-dimensionally reconstruct the renal nerves,
and explore its anatomical and histochemical characteristics in hypertensive
canine model and patients. METHODS: Renal arteries with surrounding tissue were
collected from canines and cadavers with or without hypertension. Serial renal
artery hematoxylin-eosin sections were used for three-dimensional reconstruction,
and morphological parameters were collected and analyzed. RESULTS: In
hypertensive canines, the mean renal nerve number was 26.71 +/- 5.68 versus 19.84
+/- 5.68 in controls (P = 0.02), and the middle renal nerve volume was 5.31 +/-
2.13 versus 2.60 +/- 1.00 MUl in controls (P = 0.01). Renal tissue norepinephrine
concentrations, tyrosine hydroxylase and substance P immunoreactivity in RSN, and
growth-associated protein 43 immunoreactivity in renal ganglion were
significantly increased in hypertensive canines. In humans, the renal nerve was
evenly distributed along the renal artery in a network pattern. The renal
ganglion volume was 72.75 +/- 33.43 in hypertensive patients versus 37.04 +/-
23.95 MUl in controls (P = 0.029) and the mean neuronal size in renal ganglion
was 1187.3 +/- 219.9 MUm in patients versus 714.8 +/- 142.7 MUm in controls (P =
0.002). Tyrosine hydroxylase immunoreactivity in the RSN was 0.153 +/- 0.014 in
patients versus 0.104 +/- 0.019 in controls (P = 0.013). Growth-associated
protein 43 immunoreactivity in the renal ganglion was 86 612.8 +/- 14 642.0 in
patients versus 33 469.8 +/- 15 666.8 MUm/mm in controls (P < 0.001). CONCLUSION:
Our study suggests that RSN and renal ganglion histological remodeling occurs in
individuals with hypertension and the distal segment or branches of renal artery
might be a promising therapeutic target for RSN modulation therapy.
PMID- 29957719
TI - BMI is associated with the development of chronic kidney diseases in hypertensive
patients with normal renal function.
AB - OBJECTIVE: We aimed to investigate the relationship of BMI and waist
circumference with the development of chronic kidney disease (CKD). METHODS: A
total of 12 672 hypertensive patients with estimated glomerular filtration rate
(eGFR) at least 60 ml/min per 1.73 m from the renal sub-study of the China Stroke
Primary Prevention Trial (CSPPT) were included. The primary outcome was the
development of CKD, defined as a decrease in eGFR of at least 30% and to a level
of less than 60 ml/min per 1.73 m at the exit visit, or end-stage renal disease.
A secondary outcome was rapid renal function decline, defined as an average
decline in eGFR of at least 5 ml/min/1.73 m per year. RESULTS: Over a median
follow-up of 4.4 years, the risk of the primary event (per 1 kg/m increment; OR =
1.07, 95% CI 1.02-1.14) or rapid renal function decline (per 1 kg/m increment; OR
= 1.05, 95% CI 1.01-1.08) increased with each increment of BMI. Consistently,
compared with those with normal weight (BMI <24.0 kg/m), participants with
obesity (BMI >=28.0 kg/m) had an increased risk of the primary event (OR = 1.82;
95% CI 1.15-2.90) and rapid renal function decline (OR = 1.26; 95% CI 0.95-1.67).
However, waist circumference had no obvious effect on the risk of the primary
event (per 5 cm increment: OR = 0.94, 95% CI 0.85-1.04) or rapid renal function
decline (OR = 0.96, 95% CI 0.90-1.03). CONCLUSION: Higher BMI, but not waist
circumference, was significantly associated with an increased risk of CKD
development in hypertensive patients with normal kidney function.
PMID- 29957720
TI - Early sexual experience and hypertension in US adults: results from the National
Health and Nutrition Examination Survey 2001-2016.
AB - OBJECTIVES: We examined whether the early initiation of sexual activity is
associated with hypertension in US adults, and whether the timing of first
menstruation is meaningful in regard of this association. We also assessed the
effect modification by ethnicity. METHODS: Using data from 2001 to 2016 National
Health and Nutrition Examination Survey, we included 39 788 women. The
association of age at the first sexual intercourse (FSI) and hypertension (SBP >=
130 mmHg or DBP >= 80 mmHg) was examined using multivariate logistic regression.
Effect modification by ethnicity was assessed through a cross-product interaction
term between age at FSI and ethnicity. RESULTS: Among women with FSI after their
first menstruation, the odds of hypertension decrease by 20% [95% confidence
interval (CI) -27 to -13%] in those who experienced FSI after 19 years of age,
relative to those with FSI before 19 years of age. Ethnicity significantly
modified the inverse association between age at FSI and hypertension (P value for
interaction: 0.0003). Among non-Hispanic white, having FSI aged at least 19 years
reduced the odds of hypertension by 34% (95% CI -41 to -27%). Turning to Latina
women, the FSI before 19 years of age and before first menstruation resulted to a
marked increase in the odds of hypertension [odds ratio = 1.38 (95% CI 1.15
1.65)]. In non-Hispanic black, the age at FSI was not linked to hypertension.
CONCLUSION: The FSI before 19 years of age is associated with hypertension during
adulthood in US non-Hispanic white and Hispanic women, but not in non-Hispanic
black.
PMID- 29957721
TI - Distinct factors are related to lower limb atherosclerosis in smokers and
nonsmokers.
AB - OBJECTIVE: Smoking increases the risk of peripheral artery disease, but the
mechanisms are not well established. This study evaluated the association of
local circumferential wall tension (CWT), markers of vascular remodeling and
stiffness, and traditional risk factors with popliteal and carotid plaques among
smokers and nonsmokers. METHODS: Two hundred fifty-two individuals (126 smokers
and 126 nonsmokers) underwent clinical, laboratory, and popliteal and carotid
ultrasound analysis. Popliteal and carotid CWT measures were calculated in supine
and orthostatic positions, and supine position, respectively. RESULTS: Popliteal
plaques were more common in smokers than nonsmokers (39 vs. 19%; P < 0.001).
Among smokers, popliteal plaques were not related to differences in traditional
vascular risk factors. In propensity score-adjusted models, popliteal CWT
measures were associated with local plaques in smokers, but not in nonsmokers.
Peak orthostatic CWT was the measure showing the most significant association
with popliteal plaques (beta +/- standard error = 0.91 +/- 0.28; P = 0.001).
Local CWT measures also showed a stronger association with popliteal intima-media
thickness among smokers as compared with nonsmokers. By contrast, nonsmokers with
popliteal plaques were more likely to have older age, hypertension, diabetes and
dyslipidemia, and lower arterial compliance among nonsmokers. Lastly, carotid
plaques were not independently related to local CWT among smokers. CONCLUSION:
These findings indicate that risk factors for peripheral artery disease may
differ between smokers and nonsmokers and further suggest that atherosclerosis in
lower limb arteries is directly related to local hemodynamic forces among
smokers.
PMID- 29957722
TI - Histocompatibility leukocyte antigen and organ transplantation: love and hate
relationship.
PMID- 29957723
TI - Reasons for nonadherence to the dapivirine vaginal ring: narrative explanations
of objective drug-level results.
AB - OBJECTIVE(S): MTN-020/ASPIRE trial and IPM-027/Ring Study recently proved the
dapivirine vaginal ring was safe and effective with consistent use. To optimize
the ring's impact, the barriers and facilitators to ring adherence must be
understood and addressed. METHODS: Former ASPIRE participants were stratified by
age group (18-21; 22-45) and randomly selected at seven sites in Malawi, South
Africa, Uganda and Zimbabwe, 12-17 months after trial exit. Using in-depth
interviews or focus group discussions, ring use barriers were explored using
structured guides and visual tools including individual-level depictions of
dapivirine levels detected in plasma and returned rings. RESULTS: A total of 187
were enrolled; 37% were 18-21 years when they began ASPIRE. Most (75%) had drug
level results, suggesting inconsistent ring use throughout ASPIRE. Participants
viewed themselves as adherent, while simultaneously describing regular instances
and reasons for ring removal (e.g. for sex or menses). Less adherent women
reported fears that partners would oppose the ring or feel it during sex. High
adherers expressed altruistic motivations for ring use. Women of all ages
attributed young women's nonadherence to their tendency to be less 'serious'
about the future, HIV prevention and the study; motivated predominantly by
benefits; more fearful of fertility-related consequences; and to having less
relationship control. CONCLUSION: When presented with objective adherence data,
participants provided reasons for intermittent ring use, while simultaneously
portraying themselves as consistent ring users. Further research is needed to
understand how women could use the ring in a way that fits into the context of
their relationships and their lives while still conferring adequate HIV
prophylaxis.
PMID- 29957724
TI - Risk of hepatocellular carcinoma after DAA treatment in cirrhotic HIV-HCV
coinfected patients: where do we stand?
PMID- 29957725
TI - The Fab-ulous IgM in neutralizing HIV-1.
PMID- 29957726
TI - HIV-2 in the United States: rare but not forgotten.
PMID- 29957727
TI - Small-Sided Soccer in School Reduces Postprandial Lipemia in Adolescent Boys.
AB - PURPOSE: Although laboratory-based moderate- to high-intensity exercise reduces
postprandial lipemia in adolescents, this exercise differs to the free-living
physical activities in which young people typically engage. This study compared
the effect of free-living afterschool soccer activity and treadmill exercise on
in-school postprandial lipemia in adolescent boys. METHODS: Fifteen boys (12.6 +/
0.5 yr) completed three, 2-d experimental trials. On day 1, participants rested
(CON), exercised for 48 min on a treadmill at 60% VO2peak (TM), or played 48 min
of 5-a-side soccer (SOC). On day 2, participants attended school where a
capillary blood sample determined fasting triacylglycerol ([TAG]) and glucose
([glucose]) concentrations. Participants then consumed a standardized breakfast
(0 h) and lunch (4.5 h), and blood samples were collected postprandially at 2.5,
5.0, and 7.0 h. RESULTS: Reductions in fasting [TAG] were small-moderate after TM
(-16%, 95% confidence interval [CI] = -27% to -2%, effect size [ES] = 0.46), but
large after SOC (-30%, 95% CI = -40% to -20%, ES = 1.00) compared with CON; the
concentration was also lower in SOC compared with TM (-18%, 95% CI = -29% to -5%,
ES = 0.53). On the basis of ratios of geometric means, the area under the TAG
versus time curve was 18% lower after TM (95% CI = -29% to -5%, ES = 0.51) and
25% lower after SOC (95% CI = -35% to -13%, ES = 0.76) compared with CON. By
contrast, SOC and TM were not significantly different (-9%, 95% CI = -21% to 5%,
ES = 0.25). CONCLUSION: Compared with duration-matched inactivity (CON), after
school small-sided soccer (SOC) and treadmill exercise (TM) resulted in a
similar, moderate reduction of postprandial lipemia in adolescent boys.
PMID- 29957728
TI - Resistance Exercise Selectively Mobilizes Monocyte Subsets: Role of Polyphenols.
AB - PURPOSE: To examine the impact of polyphenol supplementation on the recruitment,
mobilization, and activation of monocyte subsets after resistance exercise.
METHODS: Thirty-eight recreationally active males (22.1 +/- 3.1 yr; 173.9 +/- 7.9
cm; 77.8 +/- 14.5 kg) were assigned to 28 d of polyphenol blend (PPB)
supplementation, placebo (PL), or control (CON). Blood samples were obtained
before (PRE) postresistance exercise, immediately (IP) postresistance exercise, 1
h (1H) postresistance exercise, 5 h (5H) postresistance exercise, 24 h (24H)
postresistance exercise, and 48 h (48H) postresistance exercise (PPB/PL) or rest
(CON). Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H,
5H, and 48H. Circulating concentrations of macrophage chemoattractant protein-1
(MCP-1) and fractalkine, as well as intramuscular MCP-1 were analyzed via
multiplex assay. Changes in the proportions and expression of CD11b on monocyte
subsets were assessed via flow cytometry. RESULTS: Circulating MCP-1 increased in
PPB and PL at IP with further increases at 5H. Intramuscular MCP-1 was increased
at 1H, 5H, and 48H in all groups. Classical monocyte proportions were reduced in
PPB and PL at IP, and increased at 1H. Nonclassical monocytes were increased in
PPB and PL at IP, whereas intermediate monocytes were increased at IP, and
reduced at 1H. Intermediate monocytes were increased in PPB at 24H and 48H. CD11b
expression was reduced on PPB compared with PL and CON at PRE on intermediate and
nonclassical monocytes. CONCLUSIONS: Resistance exercise may elicit selective
mobilization of intermediate monocytes at 24H and 48H, which may be mediated by
tissue damage. Additionally, polyphenol supplementation may suppress CD11b
expression on monocyte subsets at rest.
PMID- 29957729
TI - Pediatric Amazonian Toxoplasmosis Caused by Atypical Strains in French Guiana,
2002-2017.
AB - BACKGROUND: Amazonian toxoplasmosis is a recently described form of Toxoplasma
gondii infection, characterized by severe clinical and biological features, and
involvement of atypical genetic strains circulating through a forest-based cycle.
Though mostly reported in French Guiana since 1998, this disease is probably
under-diagnosed in other areas of South America. Few data are available on its
specific features in children. METHODS: We retrospectively included all children
seen in Cayenne between 2002 and 2017, diagnosed with acute toxoplasmosis due to
an atypical strain. Clinical and biological features and risk factors of
Amazonian toxoplasmosis were recorded. RESULTS: 11 children met the inclusion
criteria. The main clinical features were fever, lymphadenopathy, hepatomegaly
and splenomegaly, as reported in adults. Less expected signs such as rhinorrhea,
pharyngitis and maculo-papular rash were also frequent. Cutaneous signs were
associated with the involvement of an genetically atypical strain. Respiratory
involvement was rare but associated with respiratory distress. Outcome was always
favorable. Treatment by pyrimethamine/sulfadiazine or
trimethoprim/sulfamethoxazole was always justified, efficient and well tolerated.
Genetic analysis suggested the involvement of wild mammals in disease
transmission, and strain-dependent virulence as one the prognosis risk factors.
CONCLUSION: As in adults, pediatric Amazonian toxoplasmosis requires a systematic
treatment. Symptoms such as skin rash, rhinorrhea and pharyngitis should not be
mistaken for viral infections, when associated with lymphadenopathy or fever.
Pediatricians working in South America should be familiar with these clinical
presentations and with the different risk factors of Amazonian toxoplasmosis.
PMID- 29957730
TI - Immunologic-Based Diagnosis of Latent Tuberculosis among Children Less Than 5
Years of Age Exposed and Unexposed to Tuberculosis in Tanzania: Implications for
Tuberculosis Infection Screening.
AB - BACKGROUND: Childhood tuberculosis (TB) is acquired following exposure to an
infectious TB case, often within the household. We prospectively screened
children 6-59 months of age, exposed and unexposed to an infectious TB case
within the same household, for latent tuberculosis infection (LTBI), in Dar es
Salaam, Tanzania. METHODS: We collected medical data and clinical specimens (to
evaluate for helminths, TB and HIV coinfections) and performed physical
examinations at enrollment and at 3-month and 6-months follow-up surveys. LTBI
was assessed using QuantiFERON (QFT) at enrollment and at 3 months. RESULTS: In
total, 301 children had complete data records (186 with TB exposure and 115
without known TB exposure). The median age of children was 26 months (range 6
58); 52% were females, and 4 were HIV-positive. Eight children (3%) developed TB
during the 6-month follow-up. We found equal proportions of children with LTBI
among those with and without exposure: 20% (38/186) vs. 20% (23/115) QFT
positive, and 2% (4/186) vs. 4% (5/115) indeterminate QFT. QFT conversion rate
was 7% (22 children) and reversion 8% (25 children). Of the TB-exposed children,
72% initiated isoniazid preventive therapy (IPT), but 61% of parents/caregivers
of children with unknown TB exposure and positive QFT refused IPT. CONCLUSIONS:
In this high burden TB setting, TB exposure from sources other than the household
was equally important as household exposure. Nearly one third of eligible
children did not receive IPT. Evaluation for LTBI in children remains an
important strategy for controlling TB, but should not be limited to children with
documented TB exposure.
PMID- 29957731
TI - Coverage of Haemophilus influenzae Type b Conjugate Vaccine for Children in
Mainland China: Systematic Review and Meta-Analysis.
AB - BACKGROUND: Use of Haemophilus influenzae type b conjugate vaccine is effective
in reducing the disease burden but its coverage in China is unclear. The aim of
this meta-analysis is to assess the coverage of Hib conjugate vaccines in
children in Mainland China. METHODS: We systematically searched Pubmed, Web of
Science, Medline, CNKI and Wanfang to identify studies assessing the the coverage
of Hib vaccine in Chinese children. Random-effects models were used to obtain
pooled estimates for Hib vaccine coverage and analyzed heterogeneity with meta
regression and subgroup analyses. RESULTS: Thirty-three studies that included
7,227,480 subjects in 12 provinces met our inclusion criteria. The pooled overall
coverage of Hib conjugate vaccine was 54.9% (95% CI: 52.9-57.0). The pooled
coverage for the non-local population (54.3%, 95%CI 52.4-56.3) was lower than
that for the local residents (62.0%, 95% CI 58.4-65.6). The region-pooled
coverage was higher in the east of China (59.7%, 95% CI: 57.3-62.1) than the
central and west parts of the country (48.5%, 95% CI: 40.6-56.4). Overall, 26.7%
(95% CI: 20.1-33.2) had 1 dose only, 14.8% (95%CI: 10.0-19.6%) had 2 doses, 13.5%
(95% CI: 9.1-17.8) had 3 doses and 14.3% (95% CI: 9.7-18.9) had 4 doses.
CONCLUSIONS: We found a low coverage of Hib conjugate vaccine, particularly for
the non-local children and those living in the central and west parts of China.
Including Hib vaccine into the national immunization program is recommended to
reduce disparities in vaccination coverage.
PMID- 29957732
TI - EWSR1-SMAD3-rearranged Fibroblastic Tumor: An Emerging Entity in an Increasingly
More Complex Group of Fibroblastic/Myofibroblastic Neoplasms.
AB - Three cases of superficial acral fibroblastic spindle cell neoplasms with EWSR1
SMAD3 fusion have been recently reported. Their differential diagnosis is broad,
primarily comprising rare tumors from the fibroblastic/myofibroblastic category.
The aim of this report is to present 4 new cases of this entity and to discuss
the appropriate differential diagnosis. Also, as the ERG antibody seems to be a
characteristic marker for these tumors, we analyzed ERG immunostaining
characteristics in potential mimics of this entity. All cases in our cohort
occurred in women aged 5 to 68 years (mean, 36.5 y). Two were located on the
hand, 1 on foot, and the last case arose on the calf. The tumor size ranged from
1 to 1.5 cm in the greatest dimension, with a mean size of 1.2 cm. Except for one
recent case, follow-up was available, ranging from 7 to 18 years (mean, 11.7 y),
with a recurrence noted in 1 case after 10 years. All tumors were subcutaneous
and showed 2 main components. One consisted of bland, spindled cells with
elongated nuclei which were round when observed on the cross-section. These cells
mostly grew in relatively hypercellular, well-organized, and intersecting
fascicles. The second component was prominently hyalinized and paucicellular, but
lacked calcifications. Both components showed either a distinct zonation pattern,
or they were randomly intermingled with each other. In all 3 analyzable tumors,
next-generation sequencing showed EWSR1-SMAD3 gene fusion in each case. By
fluorescence in situ hybridization, one tested case also revealed unbalanced
rearrangement of the EWSR1 gene. All 4 cases showed strong, diffuse nuclear
expression of ERG, whereas none of the mimics stained with this antibody except
for weak to moderate staining in calcifying aponeurotic fibromas (9/10 cases).
Two tumors showed focal weak to moderate expression of SAT-B2. The 4 herein
presented cases further broaden the clinicopathologic spectrum of tumors with
EWSR1-SMAD3 gene fusion. They also confirm that they represent a novel entity for
which we propose the name EWSR1-SMAD3-rearranged fibroblastic Tumor. Our study
also proves that in the context of fibroblastic/myofibroblastic tumors, ERG
immunohistochemistry is a relatively specific marker for these neoplasms.
PMID- 29957733
TI - Expanding the Spectrum of EBV-positive Marginal Zone Lymphomas: A Lesion
Associated With Diverse Immunodeficiency Settings.
AB - Traditionally low-grade B-cell lymphomas have been excluded from the category of
monomorphic posttransplant lymphoproliferative disorders. However, recent reports
identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas
(MZL), almost exclusively seen in the posttransplant setting. Some reported cases
responded to reduced immunosuppression, suggesting that they should be considered
as a form of posttransplant lymphoproliferative disorders. We identified 10 cases
of EBV MZL, 9 in extranodal sites and 1 presenting in lymph node. Two cases arose
following solid organ transplantation, but other settings included iatrogenic
immunosuppression for rheumatoid arthritis (2); prior chemotherapy (2);
congenital immune deficiency (1); and increased age (3), as the only potential
cause of immune dysfunction. There were 4 males and 6 females; age range 18 to
86. The atypical plasmacytoid and/or monocytoid B cells were positive for EBV in
all cases, with either latency I or II in all cases tested. Monotypic light chain
expression was shown in all with 6 cases positive for IgG, and 2 for IgM,
undetermined in 2. Clonal immunoglobulin gene rearrangement was positive in all
cases with successful amplification. MYD88 L265P was wild type in the 6 cases
tested. We show that EBV MZLs can arise in a variety of clinical settings, and
are most often extranodal. Treatment varied, but most patients had clinically
indolent disease with response to reduction of immune suppression, or
immunochemotherapy.
PMID- 29957734
TI - Comparative Evaluation of Foveal Avascular Zone on Two Optical Coherence
Tomography Angiography Devices.
AB - SIGNIFICANCE: This study compares foveal avascular zone (FAZ) geometry in healthy
eyes as imaged by two commercially available optical coherence tomography
angiography (OCTA) devices. Foveal avascular zone measurements are repeatable and
reproducible with each OCTA device, but interdevice agreement was poor. We
provide conversion factors between devices. PURPOSE: The purpose of this study
was to perform comparative evaluation of FAZ geometry in healthy eyes as imaged
by two commercially available OCTA devices. METHODS: Ninety-six eyes of 48
healthy subjects were imaged prospectively on each of two OCTA devices (DRI-OCT
[Topcon Corporation, Tokyo, Japan]; Cirrus 5000 [Carl Zeiss Meditec Inc., Dublin,
CA]). The FAZ was evaluated in the superficial capillary plexus layer of 6 * 6-mm
foveal scans by two masked observers. Intraobserver and interobserver agreement
was determined using intraclass correlation by using linear mixed models and
Bland-Altman plots. K-means clustering was used to provide conversion values
between two devices. Foveal avascular zone acircularity was calculated using
scans from each device and compared. RESULTS: The intraobserver repeatability for
DRI-OCT was 0.95 (95% confidence interval [CI], 0.90 to 0.98) for observer A and
0.92 (95% CI, 0.83 to 0.96) for observer B. Intraobserver repeatability for
Cirrus 5000 was 0.988 (95% CI, 0.972 to 0.995) for observer A and 0.993 (95% CI,
0.983 to 0.997) for observer B. The interobserver variability between observers A
and B for DRI-OCT was 0.87 (0.73 to 0.94) and for Cirrus 5000 was 0.984 (95% CI,
0.964 to 0.993). Poor interdevice agreement (0.205 [95% CI, -0.202 to 0.554]) was
noted, and conversion formulas were devised to convert FAZ area measurements from
one device to another. No significant correlation was found when comparing FAZ
acircularity indices between devices (P = .39). CONCLUSIONS: Repeatable and
reproducible FAZ area measurements were obtained with each respective OCTA
device, but interdevice agreement was poor, yet quantifiable and systematic with
calculable conversion factors between devices.
PMID- 29957735
TI - Testability Study of the Titmus V3 Test in Pre-school Children.
AB - SIGNIFICANCE: Vision screening can identify people who have vision problems
requiring a comprehensive examination. When children are screened, the most
prevalent serious problem is amblyopia secondary to uncorrected ametropia.
Screening also identifies strabismus, which can lead to loss of binocularity.
Early diagnosis permits treatment with restoration of balanced vision and
binocularity. PURPOSE: The study evaluated the testability of the Titmus V3
Vision Screener as a method to screen vision and strabismus in pre-school
children. METHODS: Pre-school children between 36 and 66 months of age underwent
vision screening in six Michigan counties. The State of Michigan screening
consists of the LEA Symbols test for visual acuity and the stereo butterfly for
near-strabismus testing. The proposed Titmus V3 screening tests were the LEA
Symbols slide for vision and near-strabismus test slide. Primary and secondary
objectives of this study were to evaluate the percentage of pre-school children
who completed the Titmus V3 screening tests for vision and near strabismus and
factors associated with an inability to complete the tests, contrasting the
pass/fail results between the state and Titmus V3 results. RESULTS: Two-hundred
sixty-three children were tested. The percentages of children unable to score on
the Titmus V3 instrument versus the state's LEA Symbols test were 16.0% and 5.3%,
respectively. The percentage of children unable to score on the Titmus V3 near
strabismus test slide was 6.9 versus 3.4% on the State of Michigan stereo
butterfly test. Younger age at testing was the most important factor associated
with the inability to complete testing. CONCLUSIONS: Because of testability
limitations and higher failure rates relative to the State of Michigan testing
methods, the Titmus V3 screening device is not a feasible alternative to the
standard methods used by the State of Michigan for vision and near-strabismus
screening among the pre-school subjects we tested.
PMID- 29957736
TI - Case Series: Bilateral Rhegmatogenous Retinal Detachments in Atopic Dermatitis.
AB - SIGNIFICANCE: Bilateral occurrence of rhegmatogenous retinal detachment is a
potentially blinding condition seen most commonly in patients with atopic
dermatitis. Poor control of the skin condition may lead to simultaneous or
sequential retinal detachment and even development of complications such as
proliferative vitreoretinopathy. PURPOSE: The purpose of this study was to
highlight the importance of the dermatologist's role in aggressive treatment of
atopic dermatitis to prevent this potentially blinding condition. CASE REPORTS: A
retrospective review of three patients with poorly controlled atopic dermatitis
at the Singapore National Eye Centre with bilateral rhegmatogenous retinal
detachment was conducted. Two patients presented with sequential rhegmatogenous
retinal detachments, and one patient had simultaneous bilateral retinal
detachments. At presentation, all three were experiencing atopic dermatitis
flares and were either on low-dose oral or topical steroids only. Post-retinal
detachment surgery, all eyes except one achieved good visual acuity. The patients
were referred to a dermatologist and treated with therapeutic doses of systemic
steroids and immunomodulators for their dermatitis flare. CONCLUSIONS: This case
series draws attention to the importance of the eye care provider's comanagement
of such patients with atopic dermatitis. Aggressive control of facial atopic
dermatitis with consideration of immunomodulators or short-term systemic steroids
during flares to control facial eczema and eye rubbing may reduce this
potentially blinding ocular complication.
PMID- 29957737
TI - Case Series: Corneal Epithelial Macrocysts in Scleral Contact Lenses Post
penetrating Keratoplasty.
AB - SIGNIFICANCE: Transitory corneal epithelial macrocysts associated with scleral
contact lens wear post-penetrating keratoplasty are observed in areas of corneal
edema. The macrocysts do not appear to result in complications that would prevent
successful wear of scleral contact lenses. PURPOSE: The purpose of this study is
to report three cases of transitory corneal epithelial macrocysts associated with
scleral lenses in post-penetrating keratoplasty corneas. CASE REPORTS: Three
cases including anterior segment photographs and anterior segment optical
coherence tomography highlight the clinical presentation of transient corneal
epithelial macrocysts. CONCLUSIONS: Corneal edema and anatomical alterations
after penetrating keratoplasty along with the negative pressure underneath a
scleral contact lens are hypothesized to have caused the transient epithelial
macrocysts observed in these cases. Because of the transitory nature of these
cysts without evidence of consequent corneal damage or cyst rupture over years of
observance, we believe that it is safe for these patients to continue wearing
scleral contact lenses with routine follow-up.
PMID- 29957738
TI - Monocular Ghost Image Offset Thresholds: Dependent on Target Size and Ghost Image
Relative Brightness.
AB - SIGNIFICANCE: This is the first report of monocular ghost image offset thresholds
measured using O optotypes. Monocular diplopia is a complaint of patients and is
the result of a variety of etiologies. Furthermore, monocular image doubling also
can be a confounding variable of vectographic stereoacuity tests, warranting an
investigation of ghost image offset thresholds. PURPOSE: To measure ghost image
offset thresholds of normal observers and how they are affected by offset
orientation, target size, and ghost image relative luminance. METHODS:
Participants were five individuals without ocular abnormalities aged 21 to 32
years. Stimuli were viewed monocularly and consisted of Sloan "O" optotypes
generated on a computer monitor with varying levels of image doubling. Ghost
image offset thresholds were determined using a spatial 2-alternative forced
choice paradigm and probit analysis of the frequency of seeing data. RESULTS:
Under close-to-optimal conditions, monocular ghost image offset thresholds ranged
between 14 and 22 arc seconds, a level that might be considered a hyperacuity.
Ghost image offset detection thresholds demonstrated a U-shaped relationship with
optotype size, with optimum thresholds occurring for optotypes sizes of
approximately -0.15 logarithmic minimum angle of resolution. There was no
measurable effect of offset orientation on ghost image offset detection
thresholds. Monocular ghost image offset detection thresholds decreased as ghost
image relative luminance increased. CONCLUSIONS: Ghost image offset detection
thresholds can be quite low even when viewing under monocular conditions and
relatively low ghost image relative luminance. This should be considered when
designing and interpreting the results of vectographic stereoacuity tests.
PMID- 29957739
TI - Interocular Asymmetry of the Ganglion Cell-inner Plexiform Layer in Diabetic
Retinopathy.
AB - SIGNIFICANCE: The interocular difference in the ganglion cell-inner plexiform
layer thickness showed a significant correlation with the diabetic retinopathy
(DR) severity. PURPOSE: The purpose of this study was to analyze the interocular
differences in the foveal, retinal nerve fiber layer (RNFL), and ganglion cell
inner plexiform layer (GC-IPL) thickness of DR patients using spectral-domain
optical coherence tomography. METHODS: A total of 508 eyes from 254 patients with
different severities of DR and 184 eyes from 92 control subjects were included.
The GC-IPL, foveal, and RNFL thicknesses were measured, and the interocular
differences in these thicknesses were correlated in control subjects and DR
patients. RESULTS: The interocular difference in the average GC-IPL thickness
significantly increased with the severity of DR. The interocular differences in
the average GC-IPL thicknesses of the severe nonproliferative DR (NPDR) and the
proliferative DR patients were significantly higher than those of the control
group. However, there was no significant difference in thickness between the
control group and the group with mild to moderate NPDR. In the group with
proliferative DR, the interocular difference in the average GC-IPL was greater
than those in the central foveal and RNFL thicknesses. Multivariate regression
analyses showed that the DR severity and the interocular difference in central
foveal thickness were significantly correlated with the interocular difference in
the average GC-IPL thickness. CONCLUSIONS: The interocular differences in the
central foveal, RNFL, and GC-IPL thicknesses significantly increased with
increased DR severity. However, there was no significant difference between the
control group and the group with mild to moderate NPDR. The GC-IPL differences
showed a significant correlation with DR severity. These findings may be an
indicator of DR progression.
PMID- 29957740
TI - Corneal Biomechanics in Unilateral Keratoconus and Fellow Eyes with a Scheimpflug
based Tonometer.
AB - SIGNIFICANCE: Before the appearance of evident keratoconus, corneal biomechanical
changes may be detectable. Here, these properties are analyzed to detect any
difference that could help in the early recognition of keratoconus to allow
patients to benefit from early treatments and to avoid refractive procedures in
these corneas. PURPOSE: The purpose of this study was to compare corneal
biomechanical characteristics as determined by Corvis Scheimpflug Technology
tonometry between normal eyes and asymmetric keratoconic eyes. METHODS:
Retrospective data from normal eyes (n = 100), keratoconic eyes (n = 18), and
their topographically normal fellow eyes (n = 18) were analyzed. Differences in
the variables among the groups were determined. For the parameters that showed
significant differences, the receiver operating characteristic curve and the area
under the curve (AUC) were used to assess the diagnostic accuracy of each
variable. The optimal cutoff points were determined when comparing normal and
fellow eyes. Also, a new linear combination of variables was performed to obtain
better discriminative values. RESULTS: The following variables differed
significantly between normal and fellow eyes: length of the flattened cornea in
the second applanation, peak distance, curvature radius at highest concavity, and
central corneal thickness. When each variable was independently considered, AUCs,
sensitivity, and specificity were insufficiently high for good discrimination
between the two groups. However, using a linear combination of variables, an
optimal cutoff point (0.157) was obtained with an AUC of 0.78, sensitivity of
0.84, and specificity of 0.69. CONCLUSIONS: A best predictive linear combination
of corneal biomechanical variables was tested including diameter of the flattened
cornea in the second applanation and central corneal thickness. This combination
was considered as the best in terms of its prediction capacity, simplicity and
clinical application. This formula may be useful in clinical practice to
discriminate between normal eyes and incipient keratoconus.
PMID- 29957741
TI - Constructing Item Banks for Measuring Quality of Life in Refractive Error.
AB - SIGNIFICANCE: Existing patient-reported outcome instruments in refractive error
are paper-based questionnaires. They are not comprehensive and psychometrically
robust. This study has identified the content of the refractive error-specific
item banks that aim to provide comprehensive and scientific measurement of
refractive error-specific quality of life. PURPOSE: The purpose of this study was
to identify minimally representative, optimally informative, and efficient sets
of items for measuring quality of life in people with refractive error. METHODS:
First, items were identified from existing patient-reported outcome instruments.
Second, items were developed from qualitative studies with people with refractive
error (48 and 101 in-depth interviews in Australia and Nepal, respectively).
Third, classification and selection of items were done based on a set of
systematic criteria using an iterative process of binning and winnowing. The
resulting items underwent cognitive testing with people with refractive error in
Australia and in Nepal. Each step was guided by an expert panel consensus.
RESULTS: We retrieved 792 items from the existing patient-reported outcome
instruments. From the interviews conducted in Australia, a total of 2367 comments
were coded into 807 initial items. Similarly, from the interviews conducted in
Nepal, 3477 comments were coded into 914 initial items. After binning and
winnowing, followed by cognitive testing, a final set of items comprising 337
items for the Item-pool (Australia) and 308 items for the Item-pool (Nepal), both
spanning 12 domains, was obtained. Forty-seven percent of items were common
across the two item pools. In the Item-pool (Nepal), 65% items were common for
corrected and uncorrected refractive error. CONCLUSIONS: We identified the
content of two different sets of item banks to comprehensively measure the impact
of refractive error on quality of life for people in Australia and Nepal, which
may be applicable to high-income country settings and low- and middle-income
country settings, respectively. Future work aims to develop computer-adaptive
testing system to administer the item banks, resulting in useful measurement
tools for researchers, clinicians, and policy planners.
PMID- 29957742
TI - A case of Nablus mask-like facial syndrome with autism spectrum disorders.
PMID- 29957743
TI - Is 472G/A catechol-O-methyl-transferase gene polymorphism related to panic
disorder?: Erratum.
PMID- 29957744
TI - Preparing for the Decade of Healthy Aging (2020-2030): prevention plus therapy?
AB - Not available.
PMID- 29957745
TI - The Italian Code of Medical Deontology. Historical, ethical and legal issues.
AB - BACKGROUND AND AIM: Medical deontology is increasingly important, owing to the
interests and rights which the medical profession involves. This paper focuses on
the relationships of the Italian Code of Medical Deontology (CMD) with both the
ethical and legal dimensions, in order to clarify the role of medical ethics
within the medical profession, society and the overall system of the sources of
law. METHODS: The authors analyze the CMD from an ethical perspective and through
the new doctrinal guidelines and current trends in the Italian law courts.
RESULTS: From an ethical point of view, moral philosophical analysis scarcely
seems to address professional medical ethics. Nonetheless, the CMD needs to
undergo careful ethical analysis. From a legal perspective, the Italian CMD
contains provisions which do not have an official legal nature. However, they
are directly binding for medical practitioners, and therefore could be understood
as a supplement to the general rules of the legal system. CONCLUSIONS: At an
ethical level, rigorous debate on the CMD is indispensable, in order to update
its specific principles and to make it a real moral normative document. At a
legislative level, there is a possible contradiction between a legal system that
does not take into account the CMD, but which then attributes significant
importance to the violation of its rules.
PMID- 29957746
TI - Lung function tests to monitor respiratory disease in preschool children.
AB - Pulmonary function tests are routinely used in the diagnosis and follow-up of
respiratory diseases. In preschool children assessment and evaluation of lung
function has always been challenging but improved techniques that require only
minimal collaboration allowed obtaining reliable and useful results even in this
group of patients. In this review we will describe the different techniques used
in clinical practice to measure lung function in preschool children.
PMID- 29957747
TI - Project design for surgical department reorganization at hospital-university of
Parma.
AB - The article explains the main technical and methodological references of the
reorganization of the main surgical activities (for production volumes and case
mixes) of the Parma University Hospital. In defining the organizational design we
considered the compliance with national laws and regional guidelines, the vision
of the Public Enterprise Strategic Management, the attempt to bring the
continuity of care through hospital paths, the valorization of the high technical
specialty of a hub university center, the recognition of the ability and
vocations of Professionals and the search for efficiency of a complex public
production system. The project has also responded to the need to pursue greater
production efficiency by the entire local health system of Parma, optimizing, at
the same time, training courses for Medical Students and Health Professions of
the University of Parma transversely with respect to surgical clinical pathways
and clinical research.
PMID- 29957748
TI - The "Canone Inverso": when tobacco was not so bad. A Look Back at the Primordial
Debate on the tobacco effects in the Occupational Medicine.
AB - AIM: The article provides an overview on the beginning and evolutions of medical
observations on tobacco induced diseases between Eighteenth and Nineteenth
century. METHODS: By searching for historical medical literature, first studies
on tobacco-induced diseases focused on production risks rather than on adverse
effects that the use of tobacco has for the human health. RESULTS: The approach
induced first eighteenth-century authors to define this substance as a non
pathogenic and, consequently, not to consider tobacco factories dangerous for
health workers. In those years, tobacco was employed in therapy as a stimulant
treatment and it was considered harmless and even healthy and preventive of
several acute diseases. CONCLUSIONS: Authors will show that studies on pathogenic
effects of smoking will only start around late nineteenth century, when the idea
of the healthiness of tobacco industry was already supported.
PMID- 29957749
TI - Scrambler therapy in the management of somatosensory signs and symptoms related
to neuropathic pain: an exploratory and prospective analysis.
AB - OBJECTIVES: Neuropathic pain is a severe and disabling health problem, often
difficult to treat and characterized by specific somatosensory signs and
symptoms. The goal of this study is to detect the effect of Scrambler therapy
(ST) on the reset of Neuropathic Pain Diagnostic Questionnaire (DN4), in a cohort
of patients affected by intense drug-resistant neuropathic pain. METHODS:
Patients with chronic neuropathic pain were consecutively enrolled to receive 45
minute daily ST for an average of 10 consecutive days. Evaluation of pain
intensity by Numerical Rating Scale (NRS) score and DN4 questionnaire was
performed at the beginning and at the end of the treatment. Primary endpoint was
to achieve a significant negativization of DN4 (DN4 <4) in the study population
after 10 ST sessions. Secondary endpoints were to detect a correlation between
DN4 negativization and pain intensity reduction >=50% (patient responders),
finally to analyse the impact of ST on each item of DN4 survey. RESULTS: We
prospectively treated 45 patients. Mean baseline DN4 score was 5.67 [+/-1.43] and
fell by 50.3%, with a mean DN4 score of 2.82 [+/-2.18] at the end of treatment
(OR 2.84; 95%CI: 2.07-3.62; p<0.0001). In 28 out of 45 (62.2%) patients we
reported a negativisation of DN4 (p<0.0001). Correlation between the percentage
of patient responders and patients with negativization of DN4 was statistically
significant (p<0.0062). Analysing each DN4 item pre- and post-ST, we reported a
significant negativization in 6 out of 10 DN4 items. DISCUSSION: Our prospective
exploratory analysis met the primary endpoint and ST seems to resolve relevant
somatosensory signs and symptoms related to neuropathic pain. Based on these
encouraging results, the next step will be to evaluate these neuropathic pain
features with dedicated tools.
PMID- 29957750
TI - Investigation of the efficacy of generic and brand-name salmeterol/fluticasone
combination in the management of asthma: a randomized comparative trial.
AB - BACKGROUND: Asthma is the most chronic inflammatory disease of the airways
worldwide. Combination therapy with inhaled fluticasone and salmeterol is a
common practice for the long-term management of asthma. Seretide(r) and Fluticort
plus(r) are two available generic and brand name products of
salmeterol/fluticasone. This study aimed to compare the efficacy and safety of
these two drugs. MATERIALS AND METHODS: In this randomized comparative, clinical
trial, 80 asthmatic patients were allocated to Fluticort plus(r) (n=40) or
Seretide(r) (n=40) for a period of 4 weeks. Patients with mild asthma were
instructed to inhale one puff each 12 hours and those with moderate asthma two
puffs every 12 hours. Respiratory volumes (assessed using spirometry), quality of
life (assessed using St. George's Respiratory Questionnaire [SGRQ]) and control
of asthmatic symptoms (assessed using asthma control test [ACT]) were evaluated
at baseline and at the end of the study. RESULTS: ACT score improved only in the
Fluticort plus(r) group (p=0.012) while it was not significantly changed in the
Seretide(r) group (p=0.178). In both treatment groups, FEV1, FEV1/FVC, and total
as well as subscale SGRQ scores were significantly improved by the end of the
study (p<0.05). Seretide(r) more efficiently improved respiratory volumes and
SGRQ score in comparison with Fluticort plus(r) (p<0.05). CONCLUSION: Our
comparative trial indicated that generic fluticasone/salmeterol product could
improve respiratory volumes, quality of life but its efficacy is lower than the
brand-name product. However, Fluticort plus(r) improved asthma control more
efficiently compared with Seretide(r).
PMID- 29957751
TI - Prevalence of candidemia and associated candida subtypes following severe sepsis
in non-neutropenic critically ill patients.
AB - BACKGROUND: Invasive candidiasis management through the rapid initiation of
appropriate antifungal therapy has been shown to be associated with the better
prognosis, improved clinical outcome and reduced mortality in critically ill
patients. Therefore, selection of an appropriate antifungal therapy should be
based on the distribution of candida species and the pattern of antifungal
resistance. This study aimed to assess the prevalence of candidemia and
associated subtypes following severe sepsis in non-neutropenic critically ill
patients. METHODS: This study was a cross-sectional study that was conducted on
severe sepsis patients stayed at least seven days in intensive care unit.
Patients less than 18 years old, pregnant and breastfeeding patients,
immunocompromised patients, neutropenic patients, patients with concurrent use of
antifungal medicines and cytotoxic agents were excluded.To asses the candidemia,
one mililiter of patients' blood sample was collected. Sample analysis was
performed by Real-Time PCR and high resolution melting curve analysis method.
RESULTS: Thirty-one critically ill patients were recruited in this study over 12
month period. Candidemia with a detection limit of 100 pg per 0.2 ml blood sample
was not recognized in any of the included patients. CONCLUSION: The present
result indicates low incidence of candidemia in the targeted intensive care
units, but other factors such as small sample size, exclusion of patients with
compromised immune system and the low fungal load at the time of sampling may
also account for our observation.
PMID- 29957752
TI - Evaluation of serum Asymmetric Dimethyl Arginine concentrations in coronary
artery disease patients without traditional cardiovascular risk factors.
AB - BACKGROUND: Previous studies have shown that Asymmetric Dimethyl Arginine (ADMA)
is increased significantly during coronary artery diseases (CAD). However it is
not clear either this increase is due to cardiovascular disease (CVD) risk
factors or ADMA is increased independently in CAD. The aim of this study is to
evaluate ADMA's plasma level as an independent biomarker in CADs. PATIENTS AND
METHODS: In current study a total of 165 subjects with no traditional CVD's RFs,
who fulfilled the inclusion and exclusion criteria, were recruited; 55 CAD+
patients which had more than 50% stenosis (CAD+); 55 CAD- patients which had less
than 50% stenosis in their coronary arteries (CAD-), based on their angiography
record and 55 healthy individuals as controls. CAD+ patients were divided into
three groups: single (SVD), double (2VD), and triple vessel (3VD) disease. Plasma
level of soluble ADMA was measured with an enzyme-linked immono sorbent assay
(ELISA) kit. RESULTS: No significant difference between ADMA's plasma levels was
found between CAD+, CAD- and healthy groups. In addition ADMA's plasma levels was
not significantly different between CAD+'s subgroups. CONCLUSIONS: The result of
this study indicates no significant relation between ADMA's plasma levels and
either presence or severity of coronary artery stenosis. Therefore, it is
presumed that ADMA may not be an independent biomarker for CADs.
PMID- 29957753
TI - Cystatin C may not be a precious predictor for coronary artery disease and its
severity: an area of uncertainty.
AB - BACKGROUND AND AIM: Cystatin C, an endogenous indicator for kidney function, may
be also an original indicator for coron Background and Aim: Cystatin C, an
endogenous indicator for kidney function, may be also an original indicator for
coronary atherosclerosis. In the current study, we intended to assess its role in
establishing the existence of coronary artery disease. We also attempted to
present the best cut off point for Cystatin C to discriminate coronary disease
from normal coronary condition. METHODS: 147 consecutive patients who were
candidate for coronary angiography were included into the study. Cystatin C was
measured using Auto-analyzer system and by Gentian kit with enzyme calorimetric
method. RESULTS: The mean level of Cystatin C in the patients with and without
coronary artery disease was 0.97+/-0.51 mg/l and 1.02+/-0.40 mg/l with no
significant difference (p=0.564). In multivariate logistic regression model, the
serum level of Cystatin C could not predict coronary artery disease (OR=1.199,
95% CI: 0.531 to 1.706, p=0.662). According to the area under the ROC curve,
Cystatin C was not a good indicator to discriminate coronary artery disease from
normal coronary condition (AUC=0.465, 95% CI: 0.372 to 0.559, p=0.470).
Considering cut of points of 0.85 and 0.94 for Cystatin C, the sensitivity of
this test for predicting coronary artery disease in comparison with coronary
angiography was 65% and 51%, respectively. In assessing relationship between
serum level of Cystatin C and other chemical biomarkers, Cystatin C was only
correlated with serum triglyceride level (r=0.207, p=0.012). CONCLUSIONS:
Cystatin C measurement may not be a suitable predictor for coronary artery
disease and severity of the coronary involvement. Future studies with large
sample size are necessitated to demarcate distinct role of Cystatin C in coronary
artery disease. ary atherosclerosis. In the current study, we intended to
assess its role in establishing the existence of coronary artery disease. We also
attempted to present the best cut off point for Cystatin C to discriminate
coronary disease from normal coronary condition. METHODS: 147 consecutive
patients who were candidate for coronary angiography were included into the
study. Cystatin C was measured using Auto-analyzer system and by Gentian kit with
enzyme calorimetric method. Results: The mean level of Cystatin C in the
patients with and without coronary artery disease was 0.97 +/- 0.51 mg/l and 1.02
+/- 0.40 mg/l with no significant difference (p = 0.564). In multivariate
logistic regression model, the serum level of Cystatin C could not predict
coronary artery disease (OR = 1.199, 95% CI: 0.531 to 1.706, p = 0.662).
According to the area under the ROC curve, Cystatin C was not a good indicator to
discriminate coronary artery disease from normal coronary condition (AUC = 0.465,
95%CI: 0.372 to 0.559, p = 0.470). Considering cut of points of 0.85 and 0.94 for
Cystatin C, the sensitivity of this test for predicting coronary artery disease
in comparison with coronary angiography was 65% and 51%, respectively. In
assessing relationship between serum level of Cystatin C and other chemical
biomarkers, Cystatin C was only correlated with serum triglyceride level (r =
0.207, p = 0.012). CONCLUSIONS: Cystatin C measurement may not be a suitable
predictor for coronary artery disease and severity of the coronary involvement.
Future studies with large sample size are necessitated to demarcate distinct role
of Cystatin C in coronary artery disease.
PMID- 29957754
TI - Beneficial effects of the treatment of iron deficiency on clinical condition,
left ventricular function, and quality of life in patients with chronic heart
failure.
AB - BACKGROUND: Anemia is now considered as an important contributing factor to the
deterioration of chronic heart failure. The present study aimed to assess the
effects of intravenous iron therapy on clinical condition, left ventricular
function and also quality of life in patients who suffered of chronic heart
failure and concomitant iron deficiency. METHODS: In this clinical trial, 25
consecutive patients with concomitant chronic heart failure and iron deficiency
referred to Shariati hospital in Isfahan, Iran in 2013. After initial clinical,
laboratory, and echocardiography assessments, the patients administered 200 mg
intravenous Iron per week until compensating iron deficit. Then, all study
parameters were assessed again and compared to parameters before the therapeutic
intervention. RESULTS: The NYHA class showed a significant improvement after the
therapeutic approach. The prevalence of heart failure-related edema was also
significantly reduced from 60% before treatment to 48% after that (p = 0.036).
The rate of hospitalization was considerably reduced from 42% to 16% (P < 0.001).
Moreover, mean 6 minute walk test (6MWT) was increased from 155.18 m to 187.40 m
(P < 0.001). Comparing Left Ventricular Ejection Fraction (LVEF) after treatment
to figures before the test indicated a significant improvement in this parameter
(27.5% versus 33.0%, P = 0.007). The treatment of iron deficiency in this group
of subjects got a significant improvement in SF36 total score. CONCLUSION: In
patients with chronic heart failure, the treatment of iron deficiency results in
a marked improvement in functional status, ejection fraction, and also quality of
life as well as a reduction in need to re-hospitalization, however renal function
was deteriorated and thus more pay attention to renal function is necessary.
PMID- 29957755
TI - Recurrence of prostate cancer after HIFU. Proposal of a novel predictive index.
AB - BACKGROUND AND AIM OF THE WORK: Prostate cancer is one of the most common cancers
in men over 50 years of age. Surgery, radiotherapy and hormonal manipulation
represent its typical treatment. High-Intensity Focused Ultrasound (HIFU) is an
alternative choice in localized prostate cancer. To date, an index for prediction
of recurrence in patients treated with HIFU is not availabe. Our study proposes a
novel index for the predition of recurrence able to determine if a candidate is
fit for this tratment. METHODS: 107 patients underwent HIFU fram 2010 to 2015. A
total of 12 variables were considered for the analysis. The final predictive
model was obtained through a stepwise forward selection method. RESULTS: The
final model used a total of 6 variables, all correlated to the response variable.
The Index is able to predict the recurrence after HIFU tratment in the most
majority of candidates to treatment. The index may be used to make a more
scientific decision with regard to choosing optimal candidates for HIFU.
PMID- 29957756
TI - Is it necessary to discontinue metformin in diabetic patients with GFR > 60
ml/min per 1.73 m2 undergoing coronary angiography: A controversy still exists?
AB - BACKGROUND: Although metformin is not directly nephrotoxic, it has been
postulated that it can impair gluconeogenesis from lactate, which may lead
lactate to be accumulated under circumstances such as contrast-induced
nephropathy. The present study aims to assess the role of metformin in lactate
production in a group of diabetic patients with GFR > 60 ml/min per 1.73
m2undergoing coronary angiography. METHODS: In the present randomized clinical
trial, 162 metformin-treated diabetic patients were enrolled. The enlisted
patients were scheduled to undergo coronary angiography at Modarres Hospital from
Feb 2012 to Nov 2012. Patients were randomly allocated to continue metformin
during peri-angiography period (M (+) group) or to stop the medication 24 hours
prior the procedure (M (-) group). All the patients had glomerular filtration
rate of >60 mL/min per 1.73 m2. Iodixanol was the only contrast media which in
all patients. Metformin-associated lactic acidosis (MALA) was defined as an
arterial pH <7.35 and plasma lactate concentration >5 mmol/L. RESULTS: 162
patients, including79 (48.7%) male and 83 (51.3%) female patients were enrolled
in the study. The average of GFR was comparable in both groups (76 ml/min per
1.73 m2 in the M (+) group versus 79 ml/min per 1.73 m2 in the M (-) group,
p=0.53). No significant difference was observed in the mean dose of metformin
before the study between the 2 groups (2.18 tablets per day in M (+) group vs.
2.21 tablets per day in M(-) group, p=0.62).No lactic acidosis was observed in
the studied groups. CONCLUSION: In conclusion, the results of the present study
indicate that metformin continuation in diabetic patients with a GFR of more than
60 ml/min per 1.73 m2 undergoing coronary angiography does not enhance the risk
of MALA development.
PMID- 29957757
TI - Could infantile interactive drawing technique be useful to promote the
communication between children with Type-1 diabetes and pediatric team?
AB - AIM: to finding what young patients with type-1 diabetes (T1D) knows about their
body and also on their illness in perspective to tailor educational interventions
to their real ability to understand. METHODS: the present study involved 68
children with T1D , 5 to 14 years old with a duration of diabetes ranging from 2
to 6 years and a total HbA1c mean value of 7.96+/-0.87%. The sample was divided
into two age Groups: 28 children 5 to 10 years old were gathered in the Group 1
and 40 teenagers aged from 11 to 14 years in the Group 2. These patients were
invited to draw over a white paper using a black pencil "The human body as it is
made inside". Subsequently they were asked to explain: "what is diabetes?" and
"where does insulin go?". According to the methodology of the "interactive
drawing", the interviewer interacted with the children while drawing, forcing
them to verbalize the reasons for their choices, to justify their proceeding, to
explain their plan and then to explicit their theories. Drawings and replies were
classified as Correct, Correct-but-Incomplete and Incorrect. RESULTS: the overall
production of correct/correct-but-incomplete drawings was 83.82% vs 16.20% of the
incorrect ones. One-hundred of the children who have produced a correct drawing
supplied also a correct verbal reply, whereas 100% of the children who have
produced an incorrect drawing was unable to supply any information on diabetes or
about insulin. Both younger and older subjects who produced a complete-but
incorrect drawing appeared to have misunderstood the action of insulin therapy
(only 23% and 17% of correct replies). Children who produced incomplete drawings
and provided incorrect replies to the questions about their disease showed also a
HbA1c mean value higher (8.36+/-0.97%) compared to the children who drew and
answered correctly (p=0.0023). CONCLUSIONS: the operative epistemic approach
could represent a promising tool for a health professional team to verify the
real understanding acquired by a child about T1D, and to provide pediatrician a
guideline to directly communicate with his patient.
PMID- 29957758
TI - Surgical therapy of cutaneous squamous cell carcinoma: our experience.
AB - INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is the second most common
skin cancer, with an excellent prognosis after surgical removal. However, nodal
metastasis are present in about 5% of cases and the death rate is about 2%.
PRESENTATION OF CASE: The aim of this study is to report our experience about the
surgical treatment of cSCC at the Cutaneous, Regenerative, Mininvasive and
Plastic Surgery Unit, University of Parma, Italy, between January 2014 and
February 2016. We statistically analyzed the group of patients regarding the
average age, gender, localization and size of the lesions. The surgical margins
of the excisions are studied and we report the results obtained after a follow up
of 3 to 25 months. DISCUSSION: Between January 2014 and February 2016 in our
Cutaneous, Regenerative, Mininvasive and Plastic Surgery Unit, we removed 36
squamous cell carcinomas, including 11 cSCCs in situ. The average annual
incidence of squamous cell carcinoma in northeast of Italy is about 28,9 cases
per 100,000 individuals.The number of cSCCs that we removed is lower than the
Italian average. In our opinion, this is due to an increase in the early
diagnosis of precancerous lesions and their medical or surgical treatment. This
reduces the incidence of squamous cell carcinomas developing from precancerous
lesions. CONCLUSION: The excision of cutaneous squamous cell carcinoma should be
undertaken with a safety margin of at least 0.9 mm to minimize recurrence and
metastasis.
PMID- 29957760
TI - Delayed, diffuse acute peritonitis secondary to misplacement of a
cystogastrostomic "pigtail" drain in an outpatient after discharge.
AB - BACKGROUND AND AIM OF THE WORK: Pancreatic pseudocyst endoscopic drainage by
pancreatogastrostomy "pigtail" drain placement is spreading worldwide, with high
success-rate and low morbidity, and is increasingly performed as outpatient
procedure. The paper reports an unusual very early complication of this procedure
and discusses the peculiar aspects of this event in an outpatient setting.
METHODS: The first case of a 56-year-old outpatient developing a postoperative
diffused acute peritonitis by gastric juice spilling caused by the misplacement
of the distal end of two transgastric drains not reaching the pseudocyst is
reported. As the case was programmed as outpatient and acute peritonitis symptoms
occurred eight hours postoperatively, the patient was discharged and
rehospitalized. A review of the literature of rare perforative complications of
pancreatogastrostomy is performed. RESULTS: CT scan allowed the prompt diagnosis,
as it showed massive pneumoperitoneum, free fluid collection, and pigtail drain
misplacement. Emergency laparoscopy allowed the removal of the two misplaced
drains and gastric reparation. The procedure lasted 65 minutes, mostly needed for
lavage. The patient was discharged 5 days later and outcomes are unremarkable 7
months after the procedure. CONCLUSION: The indication to endoscopic
pancreatogastrostomy and its outpatient management should be carefully pondered.
Pancreogastrostomy drain misplacement may cause a life-threatening acute
peritonitis associated with early aspecific symptoms, resulting in a challenging
situation, especially in an outpatient setting. CT-scan may allow prompt
diagnosis and effective management by minimally invasive surgery.
PMID- 29957759
TI - Preliminary report of the characteristics of the upper thigh spur area of the
femoral neck in Garden I and II subcapital fractures.
AB - The "heart" of the calcar is the internal cortical septum called "femoral thigh
spur". Nevertheless, the integrity of the femoral thigh spur and its extensions
in Garden I and II femoral neck fractures has not been examined in depth, in CT
scan-based studies. The aim of this retrospective study is to analyze
characteristics as integrity of upper thigh spur area of the intra-capsular
femoral neck using precise CT scans, as well as features of the medial cortical
bone interruption of orthopedic calcar, in femoral fractures that are
radiographically defined as Garden type I-II.A total number of 23 patients was
finally included in our study. We called it the "upper thigh spur area" the area
around a 360 degree perimeter of the upper thigh spur. The above-mentioned area
is a cylindrical intracapsular structure oriented parallel to the
intertrocanteric line of the proximal femur . We analyzed the modification of the
cortical bone in this specific intra-capsular area of the femoral neck. In all
the cases the upper thigh spur area (the internal cortical septum) was intact.
The medial cortical (the known "orthopedic calcar") was evaluated by CT scans in
coronal views; it was found to be interrupted in 14 patients and intact in 9;
among patients of the first group, 50% were classified as Garden I and 50% as
Garden II. The cortical integrity on 360 degrees of the upper thigh spur area
was evaluated by CT scans in axial views through different cuts, and it was found
to be intact in all cases. More extended studies including CT scans of Garden I
II-III and IV fractures are needed so as to obtain more complete results. In
conclusion, it seems that the integrity of the upper thigh spur zone is
associated with stable fractures.
PMID- 29957761
TI - Spot the trachea! A wide paratracheal air cyst of not easy definition.
AB - We report a case of a 68-year-old woman with an occasional image of a wide
paratracheal oval air cyst of not easy definition. Patient had never received a
chest X-ray and she had never suffered from symptoms that needed to investigate
the trachea or the neck. The diagnostic hypothesis was a wide tracheal
diverticulum or a bronchogenic cyst.
PMID- 29957762
TI - Charles Bonnet syndrome versus Occipital Epilepsy, a diagnostic challenge.
AB - Charles Bonnet Syndrome (CBS) is a disorder with visual deficit and complex
recurrent visual hallucination in conscious patients, described for the first
time by Charles Bonnet. It has been found in association with variable pathologic
conditions of the eyes, central visual pathways and occipital lobe. Occipital
lobe lesion is an important cause of visual field deficit associated with
elementary simple hallucinations, whereas complex hallucinations are related to
occipitotemporal and occipitoparietal visual association neocortex damage.
PMID- 29957763
TI - FNA Cytology in pediatric small cell glioblastoma.
AB - : Small cell glioblastoma is a high anaplastic variant of GBM characterized by a
monomorphic proliferation of small or medium cells with oval nuclei and scanty
cytoplasm. CASE STUDY: The cytologic findings of a small cell glioblastoma in 11
year-old male and histologic features of the tumor using immunocytohistochemistry
are reported. CONCLUSION: The accurate preoperative diagnosis of a small cell
glioblastoma is crucial to developing a curative surgical plan. Cytology-
confirmed by histology- provides a convenient, safe and effective approach to
solving a challenging differential diagnosis.
PMID- 29957765
TI - Sexual dysfunction in Neurological disorders: do we see just the tip of the
iceberg?
PMID- 29957764
TI - Periosteal osteoblastoma of the distal fibula with atypical radiological
features: a case report.
AB - We reported the case of a 22 year-old boy who suffered a periosteal osteoblastoma
of the distal fibula. The radiographic features of our case did not correlate
with the majority of periosteal osteoblastomas of the long bones reported in the
literature and were identical to a periosteal aneurysmal bone cyst. Periosteal
osteoblastoma is a very rare tumor with a wide range of clinical and radiological
features, showing in 15% of cases association with secondary aneurysmal bone
cyst. Radiologist and orthopaedic surgeon should be aware of the atypical
behavior of this rare entity in order to avoid mistakes with other more common
tumors arising on the surface of the long bones.
PMID- 29957766
TI - Nutritional prevention of cognitive decline and dementia.
AB - Cognitive impairment results from a complex interplay of many factors. The most
important independent predictor of cognitive decline is age but other
contributing factors include demographic, genetic, socio-economic, and
environmental parameters, including nutrition. The number of persons with
cognitive decline and dementia will increase in the next decades in parallel with
aging of the world population. Effective pharmaceutical treatments for age
related cognitive decline are lacking, emphasizing the importance of prevention
strategies. There is extensive evidence supporting a relationship between diet
and cognitive functions. Thus, nutritional approaches to prevent or slow
cognitive decline could have a remarkable public health impact. Several dietary
components and supplements have been examined in relation to their association
with the development of cognitive decline. A number of studies have examined the
role of dietary patterns on late-life cognition, with accumulating evidence that
combinations of foods and nutrients may act synergistically to provide stronger
benefit than those conferred by individual dietary components. Higher adherence
to the Mediterranean dietary pattern has been associated with decreased cognitive
decline and incident AD. Another dietary pattern with neuroprotective actions is
the Dietary Approach to Stop Hypertension (DASH). The combination of these two
dietary patterns has been associated with slower rates of cognitive decline and
significant reduction in incident AD. This review evaluates the evidence for the
effects of some dietary components, supplements, and dietary patterns as
neuroprotective, with potential to delay cognitive decline and the onset of
dementia.
PMID- 29957767
TI - Biogerontology: research status, challenges and opportunities.
AB - Biogerontology is the study of the biological basis of ageing and age-related
diseases. The phenomenon and the process of ageing are well understood in
evolutionary and biological terms; and a conceptual framework has been
established within which general principles of ageing and longevity can be
formulated. The phenotype of ageing in terms of progressive loss of physical
function and fitness is best seen during the period of survival after the
evolution-determined essential lifespan (ELS) of a species. However, the ageing
phenotype is highly heterogenous and individualistic at all levels from the whole
body to the molecular one. Most significantly, the process and the progression of
ageing are not determined by any specific gerontogenes. Ageing is the result of
imperfect maintenance and repair systems that allow a progressive shrinkage of
the homeodynamic space of an individual. The challenge is to develop and apply
wholistic approaches to the complex trait of ageing for maintaining and/or
improving health. One such approach is that of mild stress-induced physiological
hormesis by physical, mental and nutritional hormetins. Biogerontological
research offers numerous opportunities for developing evidence-based novel
biomedical technologies for maintaining and improving health, for preventing the
onset of age-related diseases, and for extending the health-span.
PMID- 29957768
TI - The complexity of loneliness.
AB - Loneliness is a prevalent and global problem for adult populations, and a number
of different studies have linked it to multiple chronic conditions, including:
heart disease, lung disease, cardiovascular disease, hypertension,
atherosclerosis, stroke, and metabolic disorders, such as obesity and metabolic
disease. Is a major predictor of psychological problems, such as depression,
psychological stress, and anxiety. Loneliness is linked to overall morbidity and
mortality in adult populations. But limited interventions have demonstrated long
term effectiveness in reducing loneliness in adults with these same chronic
conditions. Our research of the extant literature addresses the following
question: What evidence exists regarding the relationships between loneliness and
health? We focus on recent findings with respect to the links between loneliness
and health.
PMID- 29957769
TI - Pulse train interaction and control in a microcavity laser with delayed optical
feedback.
AB - We report experimental and theoretical results on the pulse train dynamics in an
excitable semiconductor microcavity laser with an integrated saturable absorber
and delayed optical feedback. We show how short optical control pulses can
trigger, erase, or retime regenerative pulse trains in the external cavity. Both
repulsive and attractive interactions between pulses are observed, and are
explained in terms of the internal dynamics of the carriers. A bifurcation
analysis of a model consisting of a system of nonlinear delay differential
equations shows that arbitrary sequences of coexisting pulse trains are very long
transients towards weakly stable periodic solutions with equidistant pulses in
the external cavity.
PMID- 29957770
TI - Diaphragm-free gas-pressure sensor probe based on hollow-core photonic bandgap
fiber.
AB - A diaphragm-free probe-type gas-pressure sensor is proposed and experimentally
demonstrated based on a hollow-core photonic bandgap fiber (HC-PBF) with a quartz
capillary. The section of the HC-PBF acts as a Fabry-Perot cavity, and the quartz
capillary acts as a microfluidic channel for a gas inlet. An inner diameter of
the quartz capillary (~2 MUm) smaller than the HC-PBF (~10.9 MUm) ensures a
mirror reflection and a microfluidic channel simultaneously. The sensor probe has
a minimal size (~125 MUm) and can function at gas pressures as high as 8 MPa. A
higher pressure test is limited by our gas-pressure generation devices. Excellent
stability of the sensor is observed in a long timescale, and repeatability of the
sensor is confirmed by tests of six different samples. Compared with conventional
optical fiber gas-pressure sensors, the proposed sensor involves a simple
fabrication process and can acquire probe measurements with high sensitivity
(~4.17 nm/MPa), excellent linearity (0.9999), fast response, and no hysteresis.
The proposed sensor can also function at temperatures as high as 800 degrees C,
which is beneficial for high pressure measurements in extreme conditions.
Moreover, the fast response of the sensor is attractive for dynamic pressure
measurements, which needs further study and characterization.
PMID- 29957771
TI - Semiconductor terahertz modulator arrays: the size and edge effect.
AB - A terahertz spatial modulator is the critical component for active terahertz
imaging using compressive sensing. Here small silicon pieces were put in arrays
on flexible polymer substrate to fabricate semiconductor terahertz spatial
modulators. By doing this, the inter-diffusion of photo-generated charge carriers
is prevented for better resolution, and flexibility is achieved. Since the size
of silicon is comparable to the wavelength of the terahertz wave, and the
dielectric properties of the gap are very different from silicon, the optical
modulation of each element is very different from the large silicon. In this
Letter, the terahertz wave interaction and optical modulation of the small
silicon are systematically studied by time domain spectroscopy. Notably, a strong
resonance-like absorption peak was observed in a transmittance spectrum for the
small silicon due to the size and edge effect. The spatial modulation of the
terahertz wave was also compared between the silicon array and the large silicon
samples.
PMID- 29957772
TI - Ultra-broadband tunable single- and double-mode InAs/InP quantum dot external
cavity laser emitting around 1.65 MUm.
AB - We report an ultra-wide tunable single- and double-mode InAs/InP quantum dot (QD)
external-cavity (EC) laser in a Littrow configuration. By combining the high
modal gain of the QD material in the long wavelength range and an anti
reflection/high-reflection facet coating, the entire single-mode tuning range was
increased up to 190 nm under a relatively low constant pulsed injection current.
Furthermore, the tunable range was further increased to 230 nm at different bias
currents. In addition, a mode spacing as wide as 100 nm was achieved using the
same QD-EC device in the dual-mode operation, corresponding to a frequency
difference of approximately 11 THz.
PMID- 29957773
TI - On-axis intensity modulation-free, segmented, zero-order Bessel beams with
tunable ranges.
AB - We propose and experimentally demonstrate a novel experimental scheme to generate
high on-axis peak intensity, segmented, smooth, zero-order quasi-Bessel beams
with tunable ranges. Illuminating the axicon with hollow Gaussian beams (HGBs) of
different orders, we have generated Bessel beams of varying ranges at different
positions away from the axicon. The presence of a dark core at the center of the
HGBs removes the effect of imperfection in the axicon tip. As a result, the
entire power of the input beam is transformed into a zero-order Bessel beam
without any on-axis intensity modulation. We observe the decrease in range and
increase in on-axis peak intensity of the zero-order Bessel beam with the order
of HGBs. Controlling the superposition of the HGBs of different orders to the
axicon, we have demonstrated the increase in the range of the Bessel beam. The
current technique can also produce Bessel beams of different intensity
distributions, including single-peak or multiple-peak Bessel beams. Using single
pass second-harmonic generation in nonlinear crystals of different lengths, we
have further verified the increase of on-axis peak intensity of the Bessel beam
with the order of the HGBs and the increase in the range of the Bessel beam due
to the superposed HGBs.
PMID- 29957774
TI - Fast and accurate wavefront reconstruction in two-frame phase-shifting
interferometry with unknown phase step.
AB - A fast and accurate wavefront reconstruction method for two-frame phase-shifting
interferometry is proposed. The unknown phase step between the two interferograms
is estimated directly by solving a quartic polynomial equation, and then the
phase map is readily reconstructed after obtaining the phase step. The whole
phase reconstruction process is nearly analytical and thus very fast and easy to
realize. Good performance of the proposed method is demonstrated by
reconstructing the phase maps from simulated and real fringes along with
comparisons to several existing well-established algorithms.
PMID- 29957775
TI - Micro-deformation response of a holographic sensor in highly stretchable polymer
hydrogel.
AB - A volume grating-based holographic sensor in highly stretchable PVA/AA polymer
for sensing its micro-deformation and, hence, the displacement has been studied.
One-dimensional micro-displacement induced by tensile stress is analyzed using a
diffraction spectrum in two kinds of sensor construction methods, i.e.,
transmission and reflection. The dependence of the peak wavelength on the
displacement presents a good linear relationship which provides a quantitative
sensing strategy for hydrogel micro-deformation. The available sensitivity is
better than 4 MUm/0.5 nm (displacement/wavelength shift) using a commercial
spectrometer with a resolution of 0.5 nm. Finally, the reversible deformation
response further validates the practical applicability of a holographic sensor
constructed by photosensitive hydrogel. The optical measurement of micro
displacement as a novel sensing strategy can accelerate the development of the
holographic optical element.
PMID- 29957776
TI - Ultrahigh-resolution optical vector analysis using fixed low-frequency electrical
phase-magnitude detection.
AB - An ultrahigh-resolution optical vector analyzer (OVA) is proposed and
experimentally demonstrated based on microwave photonic frequency downconversion
and fixed low-frequency electrical phase-magnitude detection. In the proposed
OVA, two optical single-sideband (OSSB) signals are generated by two RF signals
with a fixed frequency spacing. One propagates through an optical device under
test (DUT) and is then combined with the other before entering to a low-speed
photodetector. By photodetection, a low-frequency and frequency-fixed
photocurrent carrying the spectral responses is achieved. Hence, a low-frequency
electrical phase-magnitude detector is sufficient to extract the magnitude and
phase. Sweeping the frequency of the RF signals, the spectral responses of the
DUT can be obtained. As compared with the conventional OSSB- and optical double
sideband-based OVA, the proposed OVA avoids the use of high-speed photodetection
and broadband electrical phase-magnitude detection. In addition, it is inherently
immune to the measurement errors induced by high-order sidebands and has the
capability of measuring arbitrary spectral responses. In an experiment, the
proposed OVA is implemented based on an electrical phase-magnitude detector
working at 10 MHz. The measurement resolution is 1 MHz, and the measurement range
is larger than 45 GHz.
PMID- 29957777
TI - Nondestructive determination of the core size of a hollow-core photonic bandgap
fiber using Fabry-Perot interference.
AB - In this Letter, we propose a simple and nondestructive method for the
determination of the core size of a hollow-core photonic bandgap fiber (HC-PBF)
and its axial uniformity based on a Fabry-Perot cavity induced by a pair of
opposite silica-air interfaces within the hollow core. The experimental results
indicate that the core size test of the HC-PBF has a nanometer-level precision,
and its axial uniformity test has an ultimate spatial resolution of tens of
microns. The method provides an effective and precise tool for the investigation
of the hollow-core size and its longitudinal evolution.
PMID- 29957778
TI - Radiation hardened high-power Er3+/Yb3+-codoped fiber amplifiers for free-space
optical communications.
AB - The radiation responses of different high-power erbium/ytterbium-codoped fiber
amplifiers (HP-EYDFA) have been investigated up to 100 krad (SiO2) dose levels.
These devices are able to deliver 20 W of signal output power at 1565 nm by
pumping at 915 nm (43 W) radiation tolerant (Er/Yb) or radiation hardened
(ErYbCe) active few mode fibers; these performances are needed for free-space
communications between low-orbit satellites and ground transceivers. X-ray
irradiation results show that, thanks to a positive influence of the photo- and
thermal-bleaching phenomena associated with such high-power operating conditions,
the gain degradation levels of HP-EYDFA based on radiation hardened fibers remain
below 6% after 100 krad at an accelerated dose rate of 3.4 rad/s.
PMID- 29957779
TI - Unidirectional excitation of plasmonic waves via a multilayered metal-dielectric
metal Huygens' nanoantenna.
AB - Huygens' nanoantennas maintain orthogonal electric and magnetic dipole resonances
satisfying the Kerker condition and can generate directional radiation in both
the near-field and far-field regimes. Here we study a multilayered metal
dielectric-metal (MDM) Huygens' type nanoantenna which is capable of launching
surface plasmon polaritons (SPPs) unidirectionally when excited by a dipole
source. We show that the radiative decay rates of the dipole source are strongly
enhanced by the antenna, and the generated SPP waves propagate in opposite
directions at two different wavelengths. The directionality of the excited SPPs
can be switched by changing the geometry and the material composition. We further
demonstrated that the beam width of the SPP waves can be narrowed by arranging
the MDM antennas in a chain.
PMID- 29957780
TI - High-resolution, flexible, and transparent nanopore thin film sensor enabled by
cascaded Fabry-Perot effect.
AB - This Letter reports a method to significantly improve the optical resolution of
the anodic aluminum oxide (AAO) nanopore thin film sensor based on multi-cavity
Fabry-Perot interference. The newly designed sensor is fabricated by bonding a
layer of transparent polymer thin film (pTF), which is polydimethylsiloxane
(PDMS), to a transparent AAO thin film to form a flexible pTF-nanopore sensor. In
comparison with the AAO nanopore thin film sensor, the pTF-nanopore sensor shows
a much-improved quality (Q) factor and optical resolution. Typical thicknesses of
a PDMS layer and an AAO layer of the pTF-nanopore sensor are 80 MUm and 2 MUm,
respectively. The pTF-nanopore sensor used for angle detection shows a
sensitivity of 0.4 nm/deg with a resolution of 0.2 deg. The pTF-nanopore sensor
can also be used for temperature monitoring with a sensitivity of 0.2 nm/ degrees
C and a resolution of 1 degrees C.
PMID- 29957781
TI - Watt-level mid-infrared supercontinuum generation from 2.7 to 4.25 MUm in an
erbium-doped ZBLAN fiber with high slope efficiency.
AB - A watt-level mid-infrared supercontinuum (MIR-SC) spanning 2.7 to 4.25 MUm is
generated in an erbium-doped ZrF4-BaF2-LaF3-AlF3-NaF (ZBLAN) fiber amplifier
(EDZFA). A broadband fiber-based SC covering 2.2-3.1 MUm region is used to seed
the amplifier. The generated SC has a maximum output power of 1.75 W with an
overall slope efficiency of 20.5%. A normalized root mean square (RMS) in power
of 0.5% shows that our system is highly stable. This research, to the best of the
authors' knowledge, demonstrates both the record power and the record slope
efficiency of in-amplifier MIR-SC generation to date.
PMID- 29957782
TI - Sapphire/Nd:YAG composite by pulsed electric current bonding for high-average
power lasers.
AB - As a new bonding technique for high-power laser optics, pulsed electric current
bonding (PECB) of sapphire and Nd:YAG ceramics was demonstrated. The optical
properties of the composite were measured, and its microstructure at the
interface and laser performance was analyzed. The optical transmittance was equal
to the theoretical value, and the transmitted wavefront was lambda/3 (lambda=633
nm); both are appropriate values for laser applications. The microstructural
analysis indicated an absence of scattering sources such as pores or non-contact
points at the sapphire/Nd:YAG interface, and the distance of yttrium diffusion
into the sapphire was theoretically expected to be less than 10 nm, much smaller
than that of ceramic materials bonded by conventional thermal diffusion
techniques. The laser performance of the composite material showed an 18% higher
output power with almost the same threshold power and slope efficiency as a
Nd:YAG ceramic due to the sapphire-conductive cooling effect. This new PECB
technique for different transparent materials has the potential to bond large
aperture optical materials over 100 mm in diameter and could be especially
effective for fabricating active laser media for high-average-power lasers having
both high-pulse energy and high repetition rates.
PMID- 29957783
TI - Nonlinear transmission and reflection of a strong terahertz pulse by a metal
film.
AB - Nonlinear interaction of the powerful terahertz radiation pulse with metal
nanofilm is investigated. Quantitative analysis of the nonlinear interaction is
illustrated by an example of an aluminum film of a thickness of several tens of
nanometers. Rapid heating of the conduction electrons and the lattice causes
significant rise of the effective electron collision frequency. This implies a
noticeable change in reflectivity and an increase of transmissivity by an order
of magnitude.
PMID- 29957784
TI - Rotation-dependent nonlinear absorption of orbital angular momentum beams in
ruby.
AB - We investigate the effect of a rotating medium on orbital angular momentum (OAM)
carrying beams by combining a weak probe beam shifted in frequency relative to a
strong pump beam. We show how the rotational Doppler effect modifies the light
matter interaction through the external rotation of the medium. This interaction
leads to an absorption that increases with the mechanical rotation velocity of
the medium and with a rate that depends on the OAM of the light beam.
PMID- 29957785
TI - Measuring high-order optical orbital angular momentum with a hyperbolic gradually
changing period pure-phase grating.
AB - We present a method to measure the high-order orbital angular momentum (OAM)
state of a light beam with a static hyperbolic gradually changing period pure
phase grating (HGCP-PPG). From the number and orientation of the fringes of the
Hermite-Gaussian-like diffraction intensity pattern, the OAM state of the
incident Laguerre-Gaussian beam can be measured. Experimental detection of the
OAM state up to +/-100-order has been achieved. This method is highly efficient
and robust because the HGCP-PPG is adaptive to high-order OAM beam and tolerant
of the misalignment of the incident OAM beam.
PMID- 29957786
TI - 656 W Er-doped, Yb-free large-core fiber laser.
AB - A continuous-wave erbium-doped ytterbium-free fiber laser generates a record
breaking pump-power-limited output power of 656 W at ~1601 nm when cladding
pumped by 0.98 MUm diode lasers. The slope efficiency was 35.6% with respect to
launched pump power, and the beam quality factor (M2) was ~10.5. This M2 value
excludes a fraction ~25% of the power that emerged from the cladding, which we
attribute in part to mode coupling between the 146 MUm core and 700 MUm inner
cladding. Whereas these parameters are adequate for in-band tandem pumping of Tm
doped fiber lasers, we predict that an output power of over 1 kW is possible
through pumping with state-of-the-art 0.98 MUm diode lasers, even with a smaller
core that allows for improved beam quality.
PMID- 29957787
TI - Tailoring polarization singularities in a Gaussian beam with locally linear
polarization.
AB - Here we theoretically study Gaussian beams with arbitrarily located polarization
singularities (PSs). Under PSs, we mean here an isolated intensity null with
radial, azimuthal, or radial-azimuthal polarization around it. An expression is
obtained for the complex amplitude of such beams. We study in detail cases in
which there is one off-axis PS, two opposite PSs, or more than two PSs located in
the vertices of a regular polygon. If such a beam has one or two opposite PSs,
these PSs are the centers of radial polarization. If there are three PSs, then
one of them has radial polarization, and the other two have mixed radial
azimuthal polarization. If the beam has four PSs, then there are two PSs with
radial polarization and two PSs with azimuthal polarization. When propagating in
space, PSs are shown to appear in a discrete set of planes, in contrast to the
phase singularities existing in any plane. If the beam has two PSs, their
polarization is shown to transform from the radial in the initial plane to the
azimuthal in the far field. The results can find application in optical
communications by using non-uniform polarization.
PMID- 29957788
TI - Imaging through extreme scattering in extended dynamic media.
AB - Critical to navigation, situational awareness, and object identification is the
ability to image through turbid water and fog. To date, the longest imaging
ranges in such environments rely on active illumination and selection of
ballistic photons by means of time gating. Here we show that the imaging range
can be extended by using time-gated holography in combination with multi-frame
processing. Instead of simply summing the intensity of the frames, we use the
complex fields retrieved through digital holographic processing and coherently
add the frames. We demonstrate imaging through extended bodies of turbid water
and fog at one-way attenuation lengths of 13 and 13.6, respectively. Compared to
equivalent traditional time-gated systems, gated holography and coherent
processing require 20* less laser illumination power for the same imaging range.
PMID- 29957789
TI - Design of optical systems with toroidal curved detectors.
AB - We consider using toroidal curved detectors to improve the performance of imaging
optical systems. We demonstrate that some optical systems have an anamorphic
field curvature. We consider an unobscured reimaging three-mirror anastigmat as
an example (f'=960 mm, F/5.3, omegax*omegay=4 degrees *4 degrees ). By assuming
that the image is focused on a toroidal detector surface and performing
reoptimization, it becomes possible to obtain a notable gain in the image quality
up to 40% in terms of the spot root mean square radius. Through analytic
computations and finite-element analysis, we demonstrate that this toroidal shape
can be obtained by bending of a thinned detector in a relatively simple setup.
PMID- 29957790
TI - Less than 1% quantum defect fiber lasers via ytterbium-doped multicomponent
fluorosilicate optical fiber.
AB - Two ytterbium-doped fiber lasers exhibiting quantum defects of less than 1% are
demonstrated, in which pumping at wavelengths of 976.6 and 981.0 nm yielded
lasing at wavelengths of 985.7 and 989.8 nm, respectively. The multicomponent
fluorosilicate active optical fiber, fabricated using the molten core method, has
spectral characteristics similar to those of fluoride glasses, namely short
average emission wavelength and long upper state lifetime. A best-case slope
efficiency of 62.1% was obtained, matching the theoretical model very well. With
further fiber and laser optimization, slope efficiencies approaching the quantum
limit should ultimately be possible. A reduction in the quantum defect may offer
significant mitigation of issues associated with fiber heating. As such, this
work can serve as a possible direction for future scaling of high-power fiber
laser systems.
PMID- 29957791
TI - Optical-resonance-enhanced nonlinearities in a MoS2-coated single-mode fiber.
AB - Few-layer molybdenum disulfide (MoS2) has an electronic band structure that is
dependent on the number of layers and, therefore, is a very promising material
for an array of optoelectronic, photonic, and lasing applications. In this
Letter, we make use of a side-polished optical fiber platform to gain access to
the nonlinear optical properties of the MoS2 material. We show that the nonlinear
response can be significantly enhanced via resonant coupling to the thin film
material, allowing for the observation of optical modulation and spectral
broadening in the telecom band. This route to access the nonlinear properties of
two-dimensional materials promises to yield new insights into their photonic
properties.
PMID- 29957792
TI - Tomographic phosphorescence lifetime multiplexing.
AB - We present a tomographic reconstruction algorithm for recovering distributions of
multiple phosphorescent dyes within turbid media from time-resolved measurements,
using either point or spatially patterned sources and detectors. The algorithm
employs a multi-exponential analysis of time-resolved data, followed by
tomographic inversion of the decay amplitudes to recover independent yield
distributions for each lifetime present in the medium. Using Monte Carlo
simulations, we computationally demonstrate that this two-step inversion approach
provides several-fold improvement in quantitative and localization accuracy
compared to a direct inversion of the time domain phosphorescence. We also
demonstrate the tomographic reconstruction of up to three phosphorescent
lifetimes embedded in thick tissue. The proposed algorithm can allow quantitative
multiplexed tomography of luminescent and phosphorescent dyes for a wide range of
in vivo applications.
PMID- 29957793
TI - Mirror-rotation-symmetrical single-focus spiral zone plates.
AB - In this Letter, we report mirror-rotation-symmetrical single-focus spiral zone
plates (MS-SZPs) fabricated by femtosecond laser direct writing. The novel
optical element can generate a single-focus vortex beam, owing to the element's
complicated continuous surface. The MS-SZP surface possesses reverse mirror
rotation symmetry, which ensures that the transfer element has the same surface
morphology as the original element. Both the transfer element and original
element have good optical properties. The single-focus behavior was investigated
by a microscopic imaging system and found to be in good agreement with
theoretical simulation results. The innovative optical component is expected to
be widely used in optical communication, quantum computation, optical
manipulation, and other fields.
PMID- 29957794
TI - Multiaxis heterodyne vibrometer for simultaneous observation of 5 degrees of
dynamic freedom from a single beam.
AB - A multiaxis heterodyne interferometer concept is under development for
observations of 5 deg of dynamic freedom using a single illumination source. This
Letter presents a laboratory system that combines elements of heterodyne Doppler
vibrometry, holography, and digital image correlation to simultaneously quantify
in-plane translation, out-of-plane rotation, and out-of-plane displacement. The
sensor concept observes a dynamic object by mixing a single optical field with
heterodyne reference beams and collecting these combined fields at the image and
Fourier planes, simultaneously. Polarization and frequency multiplexing are
applied to separate two segments of a receive Mach-Zehnder interferometer.
Different optical configurations are utilized; one segment produces a focused
image of the optical field scattered off the object while the other segment
produces an optical Fourier transform of the optical field scattered off the
object. Utilizing the amplitude and phase from each plane allows quantification
of multiple components of transient motion using a single, orthogonal beam.
PMID- 29957795
TI - Simultaneous wideband radio-frequency self-interference cancellation and
frequency downconversion for in-band full-duplex radio-over-fiber systems.
AB - A photonic approach for simultaneous wideband radio-frequency (RF) self
interference cancellation and frequency downconversion in an in-band full-duplex
radio-over-fiber system is proposed based on a dual-polarization quadrature phase
shift keying (DP-QPSK) modulator. The upper dual-parallel Mach-Zehnder modulator
(DP-MZM) in the DP-QPSK modulator is used to cancel the self-interference
directly in the optical domain and generate two sidebands of the desired RF
signal, whereas the lower DP-MZM generates two sidebands of the local oscillator.
After detecting the combined optical signal at a photodetector, the desired RF
signal is downconverted to an intermediate frequency (IF) signal with the self
interference cancelled. The proposed approach can overcome the reappearance of
the interference signal and the power fading effect of the received signal caused
by fiber dispersion. An experiment is performed. The cancellation depth for
single frequency interference cancellation is around 58 dB, whereas that for the
wideband interference cancellation is larger than 25 dB. The fading effect of the
proposed IF transmission system is also evaluated compared with the traditional
RF transmission system.
PMID- 29957796
TI - Electrospun polymer bottle microresonators for stretchable single-mode lasing
devices.
AB - We report a simple electrospinning method to fabricate polymer bottle
microresonators, which are doped with a lasing gain material and supported by
electrospun polymer micro/nanofibers on a flexible grooved polymer substrate. The
fabricated bottle microresonators have smooth outer surfaces and high quality. By
using an interference light pump approach, single whispering gallery mode lasing
is obtained, with a side-mode suppression factor over 20 dB. By mechanically
stretching the grooved substrate, tunability of the lasing peaks is demonstrated.
Our method has the advantages of saving time and being low in cost and may have
promising applications in stretchable lasing and sensing devices.
PMID- 29957797
TI - High-speed indoor optical wireless communication system employing a silicon
integrated photonic circuit.
AB - Beam-steering-based optical wireless technologies are being widely investigated
due to the capability of providing high-speed wireless connectivity in indoor
applications. However, high-speed indoor optical wireless systems are
traditionally realized with discrete bulky components, significantly limiting
their practical applications. In this Letter, we demonstrate an infrared optical
wireless communication system employing a miniaturized silicon integrated
photonic circuit for beam steering for the first time. Experimental results show
that up to 12.5 Gb/s optical wireless communication can be achieved with error
free performance over a free-space range of 140 cm, and limited mobility of users
can be realized. The experimental results of this Letter open the way for
realizing integrated high-speed optical wireless communications.
PMID- 29957798
TI - High-detectivity optical heterodyne method for wideband carrier-envelope phase
noise analysis of laser oscillators.
AB - Broadband characterization of the carrier-envelope phase (CEP) noise spectral
density of free-running mode-locked lasers is essential for advanced low-noise
optical frequency comb designs. Here we present a direct method that utilizes an
optical heterodyne beat between a pair of repetition-rate-locked mode-locked
lasers for CEP noise characterization, without requiring an f-2f interferometer
or nonlinear optical conversion steps. A proof-of-principle experiment in a
femtosecond Yb-fiber laser achieves CEP noise spectral density characterization
with >270 dB dynamic range over a Fourier frequency range from 5 mHz to 8 MHz.
The measurement noise floor is well below 1 MUrad/?Hz, enabling dependable
detection down to a quantum-limited noise floor. The method can resolve various
noise mechanisms that cause specific CEP noise spectral shapes. The underlying
mechanisms are further analyzed in terms of spurious temporal correlation to
distinguish between technical and stochastic noise signatures. Moreover, a
Hadamard deviation analysis reveals a varying degree of frequency stability in
the measured CEP time series.
PMID- 29957799
TI - Ionization-assisted spatiotemporal localization in gas-filled capillaries.
AB - We demonstrate numerically and experimentally that intense pulses propagating in
gas-filled capillaries can undergo localization in space and time due to strong
plasma defocusing. This phenomenon can occur below or above the self-focusing
threshold Pcr as a result of ionization-induced refraction that excites higher
order modes. The constructive interference of higher-order modes leads to
spatiotemporal localization and resurgence of the intensity. Simulations show
that this confinement is more prominent at shorter wavelength pulses and for
smaller capillary diameters. Experiments with ultraviolet pulses show evidence
that this ionization-induced refocusing appears below Pcr and thus represents a
mechanism for spatiotemporal confinement without self-focusing.
PMID- 29957800
TI - Experimental implementation of generalized transitionless quantum driving.
AB - It is known that high intensity fields are usually required to implement
shortcuts to adiabaticity via transitionless quantum driving (TQD). Here, we show
that this requirement can be relaxed by exploiting the gauge freedom of
generalized TQD, which is expressed in terms of an arbitrary phase when mimicking
the adiabatic evolution. We experimentally investigate the performance of
generalized TQD in comparison to both traditional TQD and adiabatic dynamics. By
using a Yb+171 trapped ion hyperfine qubit, we implement a Landau-Zener adiabatic
Hamiltonian and its (traditional and generalized) TQD counterparts. We show that
the generalized theory provides energy-optimal Hamiltonians for TQD, with no
additional fields required. In addition, the optimal TQD Hamiltonian for the
Landau-Zener model is investigated under dephasing. Even using less intense
fields, optimal TQD exhibits fidelities that are more robust against a decohering
environment, with performance superior to that provided by the adiabatic
dynamics.
PMID- 29957801
TI - Generating and synthesizing ultrabroadband twisted light using a compact silicon
chip.
AB - Compact and broadband manipulation of spatial modes is important in applications
exploiting the space domain of light waves. Here, we demonstrate chip-scale
generation and synthesization of ultrabroadband orbital angular momentum (OAM)
modes (twisted light) on a silicon platform. By introducing a subwavelength
holographic fork grating on top of a silicon waveguide, the in-plane guided mode
is converted to the free-space OAM mode. Inputs from both sides of the waveguide
enable the synthesization of OAM modes. We also characterize wavelength-dependent
emission efficiency, offset angle, and purity with favorable performance. The
chip-scale ultrabroadband OAM generator and synthesizer may find potential
applications in multidimensional optical communications and quantum key
distribution.
PMID- 29957802
TI - Multi-wavelength add-drop filter with phase-modulated shifted Bragg grating.
AB - We present, for the first time to the best of our knowledge, a multichannel add
drop operation with a phase-modulated shifted Bragg grating based filter. The
device is realized in a silicon-on-insulator waveguide platform with TiO2 as a
coating material to reduce the refractive index contrast. The operation is shown
for three and five wavelength channels within the telecom C-band. A line width of
0.6 nm with an extinction ratio of 20 dB is achieved. The shifted Bragg grating
is modulated maintaining a modal phase-matching condition for multiple
wavelengths. The phase function is calculated with an iterative Fourier transform
algorithm. The experimental results are in very good agreement with the design.
PMID- 29957803
TI - Nonlinearity mitigation of intensity modulation and coherent detection systems.
AB - Coherent optical communication systems are still too expensive for metro and
short reach networks in the near future. Coherent detection with an intensity
modulator replacing a costly dual-polarization in-phase and quadrature modulator
could offer a good trade-off between cost and performance for metro networks. The
major performance limit of such systems is the nonlinearity. To the best of our
knowledge, this Letter offers the first known investigation on nonlinearity of a
high speed intensity modulation and coherent detection system using an integrated
laser and electro-absorption modulator. Advanced nonlinearity mitigation digital
signal processing (DSP) are proposed including a 2*1 multiple-input single-output
complex transversal Volterra feed-forward equalizer (FFE) filter, a first
proposed post-FFE noise cancellation filter taking into account both pre- and
post-cursor noise correlations based on a simple autocorrelation coefficient
calculation, and a maximum likelihood sequence estimator. The receiver DSP needs
no carrier and phase recovery that is required by a conventional coherent
receiver DSP. Results show that, compared to a simple linear FFE equalization,
the proposed nonlinear DSP enables over 8 and 4 dB improvement in optical signal
to noise ratio (OSNR) sensitivity at 7% overhead hard-decision feed-forward error
correction (FEC) and 20% overhead soft-decision FEC threshold bit error rates
(BERs), respectively, for a 56 Gb/s intensity modulation and coherent detection
system. To the best of our knowledge, a record 18 dB OSNR sensitivity at a hard
decision FEC threshold BER of 3.8*10-3 is also achieved.
PMID- 29957804
TI - Fluorescence time-resolved macroimaging.
AB - While laser scanning fluorescence lifetime imaging (FLIM) is a powerful approach
for cell biology, its small field of view (typically less than 1 mm) makes it
impractical for the imaging of large biological samples that is often required
for biomedical applications. Here we present a system that allows performing FLIM
on macroscopic samples as large as 18 mm with a lateral resolution of 15 MUm. The
performance of the system is verified with FLIM of endogenous metabolic cofactor
reduced nicotinamide adenine dinucleotide (phosphate), NAD(P)H, and genetically
encoded fluorescent protein mKate2 in a mouse tumor in vivo.
PMID- 29957805
TI - Single-shot real-time detection technique for pulse-front tilt and curvature of
femtosecond pulsed beams with multiple-slit spatiotemporal interferometry.
AB - Spatiotemporal coupling (STC) of femtosecond pulsed beams could significantly
reduce the focal-spot intensity of ultra-intense lasers. We theoretically present
a very simple method for single-shot real-time detecting pulse-front tilt,
curvature, or tilt and curvature (PFT, PFC or PFT&PFC) by using multiple-slit
spatiotemporal interferometry (MSTI). An unknown input pulsed beam is spatially
cut by a high-density multiple-slit and changed into a series of spatially
separated sub-pulses. By only measuring the spatial distribution of the
interference pattern in the far-field, PFT, PFC, or PFT&PFC can be detected.
Comparing with recent methods, no reference pulses or beams, no temporal or
spatial scanning, and no temporal or spectral measurement is required. The single
shot and spatial-only measurement will greatly simplify the real-time detection
of PFT and PFC.
PMID- 29957806
TI - Enhancing artificial sum frequency generation from graphene-gold metamolecules.
AB - The enhanced artificial sum frequency generation (SFG) is realized by graphene
gold metamolecules at the mid-infrared without any natural nonlinear material.
The unit cell of the proposed metamolecules combines an inner graphene cut-wire
meta-atom and an outer gold split-ring resonator meta-atom. In order to achieve
high efficiency of the artificial SFG, not only the novel material of graphene
with high mobility is used as the constituent material, but also the double
resonances at two fundamental frequencies are excited to form an intensive
magnetic Lorentz force. Both time domain response and frequency domain response
are analyzed numerically. Results show that the SFG efficiency is at least two
orders of magnitude larger than that of second-harmonic generation, which
involves only a single resonance. The tunability of graphene on the SFG is
studied as well. This work will facilitate the engineering of nonlinear
metamaterials, whose nonlinear properties can be customized by artificial
structuring, in their practical applications.
PMID- 29957807
TI - High-quality tailored-edge cleaving using aberration-corrected Bessel-like beams.
AB - We report on the usage of ultrashort laser pulses in the form of aberration
corrected Bessel-like beams for laser cutting of glass with bevels. Our approach
foresees inclining the material's entrance surface with respect to the processing
optics. The detailed analysis of phase distortions caused by the beam transition
through the tilted glass surface allows precompensating for occurring aberrations
using digital holography. We verify theoretical considerations by means of pump
probe microscopy and present high-quality edges in nonstrengthened silicate
glass.
PMID- 29957808
TI - Evolution of the nonlinear Raman-Nath diffraction from near field to far field.
AB - In this Letter, we studied the near-field effect of the nonlinear Raman-Nath
diffraction experimentally in a 1D periodically poled LiTaO3 crystal and
established a theoretical relationship between the nonlinear effect in the near
field and the corresponding effect in the far field. The interference of far
field spots in the near field constitutes the nonlinear Talbot self-imaging
effect. Our results not only enhance our understanding of the nonlinear Talbot
effect, but they also indicate potential applications of this effect in domain
inspection and domain design.
PMID- 29957809
TI - Compact double-part grating coupler for higher-order mode coupling.
AB - We propose and demonstrate a compact and efficient grating coupler for first
order mode fiber-to-chip coupling. The coupler is configured by a double-part
grating structure combined with a curved Y-junction by means of mode diversity.
Compared with a traditional grating coupler, the designed structure takes
advantage of minimizing the taper lengths of gratings, while performing higher
coupling efficiency and lower crosstalk. At a mere 20 MUm taper length, we
measured a peak coupling efficiency of -3.68 dB with a 1 dB bandwidth of 35 nm.
The coupling performance for the fundamental mode is also investigated. A reduced
crosstalk below -15 dB within the whole band with reasonable coupling efficiency
can be experimentally observed.
PMID- 29957810
TI - Broadband high-order mode of spoof surface plasmon polaritons supported by
compact complementary structure with high efficiency.
AB - In this work, spoof surface plasmon polaritons (SSPPs) supported by microstrip
lines with T-shaped complementary grooves are proposed. Compared with the
traditional SSPP structure based on single-conductor transmission lines, a
broadband high-order mode of SSPPs can be predicted from the dispersion diagrams.
Besides, a decrease in transverse size of 75% can be realized under the same
asymptotic frequency. Then, a smooth and simple transition, which is composed of
gradient complementary grooves, is designed to realize high-efficiency excitation
and support practical applications of the high-order mode of SSPPs. As a result,
a seamless connection with microstrip lines is easily achieved without using
flaring ground, which simplifies the design procedure. Based on the proposed
structure, a prototype of a SSPP waveguide is designed and fabricated. Both
numerical and experimental results validate efficient excitation and broadband
propagation (up to 12 GHz) of the high-order mode of SSPPs. This work will
greatly accelerate the development of advanced plasmonic integrated circuits at
microwave frequencies.
PMID- 29957811
TI - Design study of random spectrometers for applications at optical frequencies.
AB - Compact spectrometers based on disordered planar waveguides exhibit a rather high
resolution with a relatively small footprint compared to conventional
spectrometers. This is achieved by multiple scattering of light, which-if
properly engineered-significantly enhances the effective optical path length.
Here a design study of random spectrometers for TE- and TM-polarized light is
presented that combines the results of Mie theory, multiple-scattering theory,
and full electromagnetic simulations. It is shown that the performance of such
random spectrometers depends on single-scattering quantities, notably on the
overall scattering efficiency and the asymmetry parameter. Further, the study
shows that a well-developed diffusive regime is not required in practice and that
a standard integrated-optical layout is sufficient to obtain efficient devices
even for rather weakly scattering systems consisting of low index inclusions in
high-index matrices, such as pores in planar silicon-nitride-based waveguides.
This allows for both significant reductions in footprint with acceptable losses
in resolution and for device operation in the visible and near-infrared frequency
range.
PMID- 29957812
TI - Three-stage frequency conversion of sub-microsecond multiline CO laser pulse in a
single ZnGeP2 crystal.
AB - Broadband three-stage frequency conversion of multiline sub-microsecond CO laser
radiation in a single sample of ZnGeP2 crystal was experimentally and numerically
studied for the first time, to the best of our knowledge. As a result, the hybrid
laser system emitted more than 200 narrow spectral lines within the 2.4-6.2 MUm
spectral range. The measured conversion efficiencies of the first, second, and
third stages were about 4.8%, 0.4%, and 0.05%, respectively. Our numerical
simulation demonstrated that the third stage of this frequency conversion can
extend the laser system spectrum toward the shorter wavelength of 2.2 MUm.
PMID- 29957813
TI - High-quality partially coherent Bessel beam array generation.
AB - We propose a protocol for generating high-quality, partially coherent (quasi
)Bessel beam arrays with controllable beam order and spatial distributions. Our
protocol involves, apart from beam intensity shaping, coherence engineering of
recently introduced optical coherence lattices. Our theoretical results are
validated with the experimental realization of partially coherent Bessel beam
arrays. The novel beam arrays are anticipated to be useful for multi-particle
trapping and micromanipulation, optical metrology and microscopy, as well as for
3D imaging.
PMID- 29957814
TI - Addressing temporal Kerr cavity solitons with a single pulse of intensity
modulation.
AB - We experimentally and numerically study the use of intensity modulation for the
controlled addressing of temporal Kerr cavity solitons (CSs). Using a coherently
driven fiber ring resonator, we demonstrate that a single temporally broad
intensity modulation pulse applied on the cavity driving field permits systematic
and efficient writing and erasing of ultrashort cavity solitons. We use numerical
simulations based on the mean-field Lugiato-Lefever model to investigate the
addressing dynamics, and present a simple physical description of the underlying
physics.
PMID- 29957815
TI - 10 W-level gain-switched all-fiber laser at 2.8 MUm.
AB - We report a simply designed gain-switched all-fiber laser emitting a maximum
average output power of 11.2 W at 2.826 um. The corresponding extracted pulse
energy is 80 uJ at a pulse duration of 170 ns. These performances significantly
surpass previous gain-switched demonstrations and are close to the state-of-the
art Q-switched laser performances near 2.8 um, but with a much simpler and robust
all-fiber design. The spliceless laser cavity is made of a heavily erbium-doped
fluoride glass fiber and is bounded by fiber Bragg gratings written directly in
the gain fiber through the protective polymer coating.
PMID- 29957816
TI - Stereocontrolled self-assembly and photochromic transformation of lanthanide
supramolecular helicates.
AB - Stereocontrolled self-assembly of a dinuclear triple-stranded europium helicate
(Eu2L3) based on DTE-functionalized ligands has been achieved via the chiral
induction strategy. The point-chirality of the ligands is transferred to give
either Delta or Lambda metal-centers and hence leads to the overall P or M
helical senses. CD spectroscopy and NMR enantiomeric differentiation experiments
have confirmed the formation of enantiomers. Moreover, the helicates in solution
feature reversible photocyclization and cycloreversion, offering an opportunity
to develop as chiroptical switches.
PMID- 29957817
TI - Ellagic acid-borax fluorescence interaction: application for novel cyclodextrin
borax nanosensors for analyzing ellagic acid in food samples.
AB - The food industry needs cheap, fast and sensitive methods to increase the number
of analyses that are routinely carried out; for this reason, new methods are
constantly being sought. This paper describes a novel fluorescent nanosensor
based on cyclodextrin (CD) to determine ellagic acid (EA). The encapsulation of
EA in the presence of borax was studied. Firstly, the complexation of EA-borax
was tested. The stoichiometry of the EA-borax complex showed a 1 : 2 complex,
with KF1 = 2548 +/- 127 M-1 and KF2 = 302 +/- 15 M-1. Different CDs were used to
obtain a 1 : 1 : 1 CD-EA-borax complex with gamma-CD providing the best
complexation constant (KF3 = 364 +/- 18 M-1). Furthermore, when the accuracy and
sensitivity of the nanosensor were tested using a crude blueberry extract, the
CD/borax mixture provided an 18 times stronger signal than with the crude extract
alone and 7 times stronger than that obtained using borax alone.
PMID- 29957818
TI - Periodic and nonperiodic chiral self-assembled networks from 1,3,5
benzenetricarboxylic acid on Ag(111).
AB - Surface-catalyzed reactions provide a versatile route to synthesizing new 2D
materials. Here, we show that the statistical nature of an activated reaction can
lead to a diversity of intermolecular bonding motifs through partially-reacted
molecules. With increasing annealing, we observe different periodic, well-defined
phases of 1,3,5-benzenetricarboxylic acid on Ag(111), where the surface structure
in each case is defined by the degree of deprotonation of the carboxylic groups.
Over a wide range of deprotonation levels (~50% to near 100%), we observe a
granular alloy comprising two distinct phases in a continuous network. This
ordered phase lacks well-defined translational symmetry, is stabilized through
both intermolecular interactions and epitaxy, and demonstrates a design approach
to creating non-crystalline phases by capitalizing on the chemical diversity of
partially reacted molecules on a surface.
PMID- 29957819
TI - Shaping monodispersed azo molecular glass microspheres using polarized light.
AB - Azo molecular glass (IAC-4) microspheres with a monodispersed diameter over ten
microns were fabricated by microfluidics and unique shape manipulation was
achieved based on their fascinating photoinduced deformation behaviour. After
irradiation with a polarized laser beam (lambda = 488 nm), the IAC-4 microspheres
were transformed into uniform mushroom-like particles, and their three
dimensional (3D) asymmetric shapes were precisely manipulated by adjusting the
irradiation time and the polarization state of light. By observing the particle
morphology in three orthogonal views (top view, front view and side view) by
scanning electron microscopy (SEM), the photoinduced deformation behaviour of the
ten-micron-sized particles was comprehensively revealed in the 3D space for the
first time. It was observed that the photoinduced deformation asymmetrically
occurred on the upper part of the microspheres due to the strong optical
absorption of the azo chromophores. Besides, the deformation manner of the upper
part was decided by the direction of the electric vibration of the refracted
light. This work not only depicts a clear picture of the photoinduced deformation
behaviour of the ten-micron-sized azo particles upon polarized light irradiation,
but also provides a new method to controllably manipulate the particle shape from
spheres to complex 3D architectures.
PMID- 29957820
TI - Electrical conductivity and oxygen diffusion behaviour of the
(La0.8Sr0.2)0.95CrxFe1-xO3-delta (x = 0.3, 0.5 and 0.7) A-site deficient
perovskites.
AB - Lanthanum strontium chromite ferrite ((La0.8Sr0.2)0.95CrxFe1-xO3-delta, LSCrF)
pellets with 5% A-site deficiency were fabricated and the electrical conductivity
and oxygen diffusion behaviour with different Cr substitution levels (x = 0.3,
0.5 and 0.7) were investigated. As the Cr content increased, the electrical
conductivity increased and then a maximum value was achieved at x = 0.7. In the
oxygen diffusion studies, all the measured materials present good surface
exchange rates (>9 * 10-8 cm s-1 at 900 degrees C) while the bulk diffusivity of
the investigated materials decreased as the Cr substitution level increased: at
900 degrees C the oxygen diffusion coefficients of the LSCrF materials (x = 0.3,
0.5 and 0.7) are 1.1 * 10-10 cm2 s-1, 3.7 * 10-12 cm2 s-1 and 8.6 * 10-13 cm2 s
1, respectively. Oxygen diffusion in the perovskite materials (LSCrF) is shown to
be bulk diffusion limited and it was found that analysis on this type of material
using the line scan mode in Time-of-Flight Secondary Ion Mass Spectrometry may
result in significant underestimation of the surface exchange coefficient due to
the oxygen saturation, while the depth profile mode provides more reliable
results but the obtained surface exchange coefficients may also only reach a
lower limit. Moreover, fast grain boundary diffusion behaviour was observed in
the LSCrF (x = 0.7) material and the Le Claire, and Chung and Wuensch
approximations were applied to analyse the oxygen diffusion profiles. For this
material, the two approximations provided similar results for the grain boundary
product (Dgbdelta) and under the assumption that the width of a grain boundary is
on the nanometre scale, the oxygen diffusion coefficient of the grain boundaries
was about 3-4 orders of magnitude higher than that of the bulk at temperatures
<=900 degrees C.
PMID- 29957821
TI - Immunosuppressive treatment for proliferative lupus nephritis.
AB - BACKGROUND: Cyclophosphamide, in combination with corticosteroids, has been first
line treatment for inducing disease remission for proliferative lupus nephritis,
reducing death at five years from over 50% in the 1950s and 1960s to less than
10% in recent years. Several treatment strategies designed to improve remission
rates and minimise toxicity have become available. Treatments, including
mycophenolate mofetil (MMF) and calcineurin inhibitors, alone and in combination,
may have equivalent or improved rates of remission, lower toxicity (less alopecia
and ovarian failure) and uncertain effects on death, end-stage kidney disease
(ESKD) and infection. This is an update of a Cochrane review first published in
2004 and updated in 2012. OBJECTIVES: Our objective was to assess the evidence
and evaluate the benefits and harms of different immunosuppressive treatments in
people with biopsy-proven lupus nephritis. The following questions relating to
management of proliferative lupus nephritis were addressed: 1) Are new
immunosuppressive agents superior to or as effective as cyclophosphamide plus
corticosteroids? 2) Which agents, dosages, routes of administration and duration
of therapy should be used? 3) Which toxicities occur with the different treatment
regimens? SEARCH METHODS: We searched the Cochrane Kidney and Transplant
Specialised Register up to 2 March 2018 with support from the Cochrane
Information Specialist using search terms relevant to this review. Studies in the
Specialised Register are identified through searches of CENTRAL, MEDLINE, and
EMBASE, conference proceedings, the International Clinical Trials Register
(ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised
controlled trials (RCTs) and quasi-RCTs comparing any immunosuppressive treatment
for biopsy-proven class III, IV, V+III and V+VI lupus nephritis in adult or
paediatric patients were included. DATA COLLECTION AND ANALYSIS: Data were
abstracted and the risks of bias were assessed independently by two authors.
Dichotomous outcomes were calculated as risk ratio (RR) and measures on
continuous scales calculated as mean differences (MD) with 95% confidence
intervals (CI). The primary outcomes were death (all causes) and complete disease
remission for induction therapy and disease relapse for maintenance therapy.
Evidence certainty was determined using GRADE. MAIN RESULTS: In this review
update, 26 new studies were identified, to include 74 studies involving 5175
participants overall. Twenty-nine studies included children under the age of 18
years with lupus nephritis, however only two studies exclusively examined the
treatment of lupus nephritis in patients less than 18 years of age.Induction
therapy Sixty-seven studies (4791 participants; median 12 months duration (range
2.5 to 48 months)) reported induction therapy. The effects of all treatment
strategies on death (all causes) and ESKD were uncertain (very low certainty
evidence) as this outcome occurred very infrequently. Compared with intravenous
(IV) cyclophosphamide, MMF may have increased complete disease remission (RR
1.17, 95% CI 0.97 to 1.42; low certainty evidence), although the range of effects
includes the possibility of little or no difference.Compared to IV
cyclophosphamide, MMF is probably associated with decreased alopecia (RR 0.29,
95% CI 0.19 to 0.46; 170 less (129 less to 194 less) per 1000 people) (moderate
certainty evidence), increased diarrhoea (RR 2.42, 95% CI 1.64 to 3.58; 142 more
(64 more to 257 more) per 1000 people) (moderate certainty evidence) and may have
made little or no difference to major infection (RR 1.02, 95% CI 0.67 to 1.54; 2
less (38 less to 62 more) per 1000 people) (low certainty evidence). It is
uncertain if MMF decreased ovarian failure compared to IV cyclophosphamide
because the certainty of the evidence was very low (RR 0.36, 95% CI 0.06 to 2.18;
26 less (39 less to 49 more) per 1000 people). Studies were not generally
designed to measure ESKD.MMF combined with tacrolimus may have increased complete
disease remission (RR 2.38, 95% CI 1.07 to 5.30; 336 more (17 to 1048 more) per
1000 people (low certainty evidence) compared with IV cyclophosphamide, however
the effects on alopecia, diarrhoea, ovarian failure, and major infection remain
uncertain. Compared to standard of care, the effects of biologics on most
outcomes were uncertain because of low to very low certainty of
evidence.Maintenance therapyNine studies (767 participants; median 30 months
duration (range 6 to 63 months)) reported maintenance therapy. In maintenance
therapy, disease relapse is probably increased with azathioprine compared with
MMF (RR 1.75, 95% CI 1.20 to 2.55; 114 more (30 to 236 more) per 1000 people
(moderate certainty evidence). Multiple other interventions were compared as
maintenance therapy, but patient-outcome data were sparse leading to imprecise
estimates. AUTHORS' CONCLUSIONS: In this review update, studies assessing
treatment for proliferative lupus nephritis were not designed to assess death
(all causes) or ESKD. MMF may lead to increased complete disease remission
compared with IV cyclophosphamide, with an acceptable adverse event profile,
although evidence certainty was low and included the possibility of no
difference. Calcineurin combined with lower dose MMF may improve induction of
disease remission compared with IV cyclophosphamide, but the comparative safety
profile of these therapies is uncertain. Azathioprine may increase disease
relapse as maintenance therapy compared with MMF.
PMID- 29957823
TI - Discovering cellular protein-protein interactions: Technological strategies and
opportunities.
AB - The analysis of protein interaction networks is one of the key challenges in the
study of biology. It connects genotypes to phenotypes, and disruption often leads
to diseases. Hence, many technologies have been developed to study protein
protein interactions (PPIs) in a cellular context. The expansion of the PPI
technology toolbox however complicates the selection of optimal approaches for
diverse biological questions. This review gives an overview of the binary and co
complex technologies, with the former evaluating the interaction of two co
expressed genetically tagged proteins, and the latter only needing the expression
of a single tagged protein or no tagged proteins at all. Mass spectrometry is
crucial for some binary and all co-complex technologies. After the detailed
description of the different technologies, the review compares their unique
specifications, advantages, disadvantages, and applicability, while highlighting
opportunities for further advancements.
PMID- 29957822
TI - Differential impact of trait sluggish cognitive tempo and ADHD inattention in
early childhood on adolescent functioning.
AB - BACKGROUND: Sluggish cognitive tempo (SCT) is distinct from attention
deficit/hyperactivity disorder inattention (ADHD-IN) and concurrently associated
with a range of impairment domains. However, few longitudinal studies have
examined SCT as a longitudinal predictor of adjustment. Studies to date have all
used a relatively short longitudinal time span (6 months to 2 years) and only
rating scale measures of adjustment. Using a prospective, multi-method design,
this study examined whether SCT and ADHD-IN were differentially associated with
functioning over a 10-year period between preschool and the end of ninth grade.
METHODS: Latent state-trait modeling determined the trait variance (i.e.
consistency across occasions) of SCT and ADHD-IN across four measurement points
(preschool and the end of kindergarten, first grade, and second grade) in a large
population-based longitudinal sample (N = 976). Regression analyses were used to
examine trait SCT and ADHD-IN factors in early childhood as predictors of
functioning at the end of ninth grade (i.e. parent ratings of psychopathology and
social/academic functioning, reading and mathematics academic achievement scores,
processing speed and working memory). RESULTS: Both SCT and ADHD-IN contained
more trait variance (Ms = 65% and 61%, respectively) than occasion-specific
variance (Ms = 35% and 39%) in early childhood, with trait variance increasing as
children progressed from preschool through early elementary school. In regression
analyses: (a) SCT significantly predicted greater withdrawal and
anxiety/depression whereas ADHD-IN did not uniquely predict these internalizing
domains; (b) ADHD-IN uniquely predicted more externalizing behaviors whereas SCT
uniquely predicted fewer externalizing behaviors; (c) SCT uniquely predicted
shyness whereas both SCT and ADHD-IN uniquely predicted global social
difficulties; and (d) ADHD-IN uniquely predicted poorer math achievement and
slower processing speed whereas SCT more consistently predicted poorer reading
achievement. CONCLUSIONS: Findings of this study - from the longest prospective
sample to date - provide the clearest evidence yet that SCT and ADHD-IN often
differ when it comes to the functional outcomes they predict.
PMID- 29957824
TI - Individualized Pharmacokinetic Dosing of Vancomycin Reduces Time to Therapeutic
Trough Concentrations in Critically Ill Patients.
AB - Dosing vancomycin in critically ill patients often results in subtherapeutic and
supratherapeutic trough concentrations. In this retrospective study, we compared
the time to goal trough attainment and incidence of acute kidney injury in
intensive care unit (ICU) patients whose vancomycin was dosed by a pharmacy
pharmacokinetic (PK) dosing and monitoring service to the standard of care. Three
hundred fifty adult ICU patients at a Level 1 trauma, teaching hospital who
received vancomycin for >24 hours from February 1, 2016, to November 30, 2016,
were screened. Patients were included in the PK group if consecutive serum
concentrations were used to calculate individualized PK and determine a dosing
regimen. Patients who were dosed using troughs only were then matched 1-to-1 to
the PK group by date of vancomycin initiation and included in the traditional
group. Fifty patients were included in each group. Baseline characteristics were
similar, except the PK group had more patients under the care of the neuromedical
ICU service (42% vs 18%; P = .02) and fewer patients with a corrected creatinine
clearance <30 mL/min/1.73 m2 (22% vs 46%; P = .02). Attainment of goal trough
concentrations for the PK and traditional groups were 84.4% and 29.4% by 48 hours
(P = .0001), 88.4% and 60.7% by 72 hours (P = .009), and 92.9% and 77.8% by 96
hours (P = .1), respectively. Incidence of acute kidney injury between the PK and
traditional groups was not statistically significant (8.3% vs 14%; P = .5).
Utilization of individualized pharmacokinetic dosing of vancomycin in critically
ill patients resulted in faster goal trough attainment without an increase in
nephrotoxicity.
PMID- 29957825
TI - Arterial stiffness is associated with visceral fat mass in kidney transplanted
patients-A nationwide cohort study.
AB - Arterial stiffness, visceral fat, and hyperglycemia are acknowledged risk factors
for adverse outcomes after transplantation, but whether arterial stiffness is
associated with visceral adipose tissue and hyperglycemia is unknown. We studied
162 non-diabetic kidney transplant recipients 8-10 weeks after transplantation.
Arterial stiffness was measured as pulse wave velocity (PWV) by SphygmoCor and
visceral fat using a validated software applied on DXA scans. Also a standard
oral glucose tolerance test was performed. Median PWV was 8.6 m/s (IQR 7.3-10.4
m/s). Patients in the upper quartile of PWV had 31%-106% higher visceral fat
percentage (P < 0.001), they were older (P < 0.001) and had a fasting plasma
glucose of 5.8 mmol/L that was higher than in the other quartiles (P = 0.006). In
univariate analysis, visceral fat percentage and age were the parameters
strongest associated with PWV (P < 0.001), but cholesterol and glucose were also
significant (P < 0.05). In multivariate analysis, visceral fat was the only
significant predictor of PWV along with age (P < 0.001). In conclusion, arterial
stiffness is significantly associated with visceral fat but not hyperglycemia in
non-diabetic kidney transplant patients. We identified age and VAT as risk
variables for arterial stiffness. A potential reversibility of arterial wall
stiffness with reduction in VAT needs further study.
PMID- 29957827
TI - Dynamics of antibiotic resistance with special reference to Shiga toxin-producing
Escherichia coli infections.
AB - The discovery of antibiotics was paralleled by the evolution of antibiotic
resistance which is probably the best example of contemporary evolution in
action. The selection pressure, imposed by indiscriminate use of antibiotics, has
changed the scale, mode and tempo of antibiotic resistance evolution. The
presence of multidrug resistance, wide range of adaptability features and the
infectivity make antibiotic resistance of Shiga toxin-producing Escherichia coli
(STEC) more dangerous. The characterization, prevalence and the virulence factors
of STEC have been profusely reported, whereas, the antibiotic resistance has been
largely ignored because the antibiotic use in STEC infections is controversial.
Thus, the current review has focussed on the source, evolution, persistence,
mechanism, dissemination and control of antibiotic resistance viz-a-viz the STEC
infections. The resistance development occurs by the inactivation of antibiotics,
regulating the membrane permeability, modification of natural antibiotic targets
or the use of efflux pumps against antibiotics. And, the dissemination of
resistance genes occurs vertically by DNA replication and horizontally by
conjugation, transduction and transformation. The prevention of development and
dissemination of antibiotic resistance needs international public health bodies
to rationalize the antibiotic use, prevent the flux of antibiotics into the
environment, develop the rapid diagnostics tests, undertake proper surveillance
of antibiotic resistance, promote the research on antibiotic resistance
prevention, promote the research and development of novel alternative
antibiotics, and encourage the widespread social awareness campaigns against the
inappropriate antibiotic usage.
PMID- 29957826
TI - Pleiotropic effects of regulatory variation in tan result in correlation of two
pigmentation traits in Drosophila melanogaster.
AB - Traits with a common genetic basis frequently display correlated phenotypic
responses to selection or environmental conditions. In Drosophila melanogaster,
pigmentation of the abdomen and a trident-shaped region on the thorax are
genetically correlated. Here, we used a pooled replicated genomewide association
approach (Pool-GWAS) to identify the genetic basis of variation in thoracic
trident pigmentation in two Drosophila melanogaster populations. We confirmed the
previously reported large effect of ebony and the association of the cosmopolitan
inversion In(3R)Payne. For the first time, we identified tan as another major
locus contributing to variation in trident pigmentation. Intriguingly, the
regulatory variants of tan that were most strongly associated with female
abdominal pigmentation also showed a strong association with trident
pigmentation. We validated this common genetic basis in transgenic assays and
found qualitatively similar effects on trident and abdominal pigmentation.
Further work is required to determine whether this genetic correlation is
favoured by natural selection or reflects a neutral by-product of a shared
regulatory architecture.
PMID- 29957828
TI - Serum vascular endothelial growth factor receptor 3 as a potential biomarker in
psoriasis.
AB - To discover novel biomarkers of psoriasis, a target-specific antibody array
screening of serum samples from psoriasis patients was initially performed. The
results revealed that vascular endothelial growth factor receptor 3 (VEGFR-3) was
significantly elevated in the sera of psoriasis patients, compared to healthy
controls. Next, ELISA validation studies in a larger cohort of psoriasis patients
(N = 73) were conducted, which confirmed that serum VEGFR-3 was indeed
significantly increased in patients with psoriasis compared to healthy controls
(P < 0.001). Furthermore, receiver operating characteristic curve analysis
demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy
controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In
addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity
Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum
VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non
psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that
serum levels of VEGFR-3 could reflect disease progression in psoriasis.
Collectively, serum VEGFR-3 may have a clinical value in monitoring disease
activity of psoriasis.
PMID- 29957829
TI - Racial Differences in Relative Skeletal Muscle Mass Loss During Diet-Induced
Weight Loss in Women.
AB - OBJECTIVE: It is unclear whether there are race-specific differences in the
maintenance of skeletal muscle during energy restriction. Changes in relative
skeletal muscle index (RSMI; limb lean tissue divided by height squared) were
compared following (1) diet alone, (2) diet + aerobic training, or (3) diet +
resistance training. METHODS: Overweight, sedentary African American (AA; n = 72)
and European American (EA; n = 68) women were provided an 800-kcal/d diet to
reduce BMI < 25 kg/m2 . Regional fat-free mass was measured with dual-energy x
ray absorptiometry. Steady-state VO2 and heart rate responses during walking were
measured. RESULTS: AA women had greater RSMI and preserved RSMI during diet
alone, while RSMI was significantly reduced among EA women (EA women -3.6% vs. AA
women + 1.1%; P < 0.05). Diet + resistance training subjects retained RSMI (EA
women + 0.2% vs. AA women + 1.4%; P = 50.05), whereas diet + aerobic training
subjects decreased RSMI (EA women -1.4% vs. AA women -1.5%; P < 0.05).
Maintenance of RSMI was related to delta walking ease and economy. CONCLUSIONS:
Compared with AA women, EA women are less muscular and lose more muscle during
weight loss without resistance training. During diet-induced weight loss,
resistance training preserves skeletal muscle, especially among premenopausal EA
women. Maintenance of muscle during weight loss associates with better ease and
economy of walking.
PMID- 29957830
TI - Metal-Organic Framework Based Microcapsules.
AB - MOFs are a type of ideal crystalline material with rigid reticular structures
whereas microcapsules are usually prepared from soft mater, such as polymers or
supramolecules. The synthesis of MOF-based microcapsules with novel
nanostructures at the molecular scale remains a great challenge. Herein, we
develop a competitive coordination strategy to synthesize MOF-based microcapsules
with novel bowl-like structures. During the competitive coordination process, the
infinite structures of MOFs are partially broken by the competitive reagents,
thus flexibility is introduced into the rigid skeletons and results in the
formation of bowl-like microcapsules. Owing to the unique structure and
composition of these nano-structures, the microcapsules exhibit excellent
performance and stability in adsorbing and removing iodine for both vapor and
solution. This work describes new opportunities in designing MOF-based
microcapsules with novel structures.
PMID- 29957831
TI - Hierarchical Cobalt-Based Metal-Organic Framework for High-Performance Lithium
Ion Batteries.
AB - In the present work, a simple solvothermal method is developed for the synthesis
of hierarchical Co-based metal-organic framework (H-Co-MOF) microflowers. These
microflowers are composed of nanosheets, consisting of small nanoflakes. Upon
application as an electrode material in Li-ion batteries, H-Co-MOF shows
ultrahigh specific capacity and long cycling performance. For instance, a
remarkably superior capacity of 1345 mA h g-1 can be achieved after 100 cycles at
a current density of 0.1 A g-1 . Even at 2 A g-1 , a large capacity of 828 mA h g
1 is maintained after 700 cycles. This excellent electrochemical performance
might be ascribed to the intrinsic properties and unique hierarchical structure
of the Co-based MOF.
PMID- 29957832
TI - Osteoporotic Vertebral Fracture Prevalence Varies Widely: Reply Letter to the
Editor.
PMID- 29957834
TI - Matching and Regression to the Mean in Difference-in-Differences Analysis.
AB - OBJECTIVE: To demonstrate regression to the mean bias introduced by matching on
preperiod variables in difference-in-differences studies. DATA SOURCES: Simulated
data. STUDY DESIGN: We performed a Monte Carlo simulation to estimate the effect
of a placebo intervention on simulated longitudinal data for units in treatment
and control groups using unmatched and matched difference-in-differences
analyses. We varied the preperiod level and trend differences between the
treatment and control groups, and the serial correlation of the matching
variables. We assessed estimator bias as the mean absolute deviation of estimated
program effects from the true value of zero. PRINCIPAL FINDINGS: When preperiod
outcome level is correlated with treatment assignment, an unmatched analysis is
unbiased, but matching units on preperiod outcome levels produces biased
estimates. The bias increases with greater preperiod level differences and weaker
serial correlation in the outcome. This problem extends to matching on preperiod
level of a time-varying covariate. When treatment assignment is correlated with
preperiod trend only, the unmatched analysis is biased, and matching units on
preperiod level or trend does not introduce additional bias. CONCLUSIONS:
Researchers should be aware of the threat of regression to the mean when
constructing matched samples for difference-in-differences. We provide guidance
on when to incorporate matching in this study design.
PMID- 29957833
TI - Inhibition of stromal-interacting molecule 1-mediated store-operated Ca2+ entry
as a novel strategy for the treatment of acquired imatinib-resistant
gastrointestinal stromal tumors.
AB - Imatinib has revolutionized the treatment of gastrointestinal stromal tumors
(GIST); however, primary and secondary resistance to imatinib is still a major
cause of treatment failure. Multiple mechanisms are involved in this progression.
In the present study, we reported a novel mechanism for the acquired resistance
to imatinib, which was induced by enhanced Ca2+ influx via stromal-interacting
molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE). We found that the
STIM1 expression level was related to the acquired resistance to imatinib in our
studied cohort. The function of STIM1 in imatinib-resistant GIST cells was also
confirmed both in vivo and in vitro. The results showed that STIM1 overexpression
contributed to SOCE and drug response in imatinib-sensitive GIST cells. Blockage
of SOCE by STIM1 knockdown suppressed the proliferation of imatinib-resistant
GIST cell lines and xenografts. In addition, STIM1-mediated SOCE exerted an
antiapoptotic effect via the MEK/ERK pathway. The results from this study provide
a basis for further research into potential novel therapeutic strategies in
acquired imatinib-resistant GIST.
PMID- 29957835
TI - Persistent hypoglycemia associated with lipid storage myopathy in a paint foal.
AB - A 12-hours-old Paint filly was examined because of weakness and dull mentation
after birth. Despite IV administered dextrose, the foal remained persistently
hypoglycemic with increase in serum activity of muscle and liver enzymes. A
postmortem diagnosis of lipid myopathy most similar to multiple acyl-CoA
dehydrogenase deficiency (MADD) was confirmed by findings of myofiber lipid
accumulation, elevated urine organic acids, and serum free acylcarnitines with
respect to control foals. This report details a case of equine neonatal lipid
storage myopathy with many biochemical characteristics of MADD. Lipid storage
myopathies should be included as a differential diagnosis in foals with
persistent weakness and hypoglycemia.
PMID- 29957836
TI - Reproductive performance and diving behaviour share a common sea-ice
concentration optimum in Adelie penguins (Pygoscelis adeliae).
AB - The Southern Ocean is currently experiencing major environmental changes,
including in sea-ice cover. Such changes strongly influence ecosystem structure
and functioning and affect the survival and reproduction of predators such as
seabirds. These effects are likely mediated by reduced availability of food
resources. As such, seabirds are reliable eco-indicators of environmental
conditions in the Antarctic region. Here, based on 9 years of sea-ice data, we
found that the breeding success of Adelie penguins (Pygoscelis adeliae) reaches a
peak at intermediate sea-ice cover (ca. 20%). We further examined the effects of
sea-ice conditions on the foraging activity of penguins, measured at multiple
scales from individual dives to foraging trips. Analysis of temporal organisation
of dives, including fractal and bout analyses, revealed an increasingly
consistent behaviour during years with extensive sea-ice cover. The relationship
between several dive parameters and sea-ice cover in the foraging area appears to
be quadratic. In years of low and high sea-ice cover, individuals adjusted their
diving effort by generally diving deeper, more frequently and by resting at the
surface between dives for shorter periods of time than in years with intermediate
sea-ice cover. Our study therefore suggests that sea-ice cover is likely to
affect the reproductive performance of Adelie penguins through its effects on
foraging behaviour, as breeding success and most diving parameters share a common
optimum. Some years, however, deviated from this general trend, suggesting that
other factors (e.g. precipitation during the breeding season) might sometimes
become preponderant over the sea-ice effects on breeding and foraging
performance. Our study highlights the value of monitoring fitness parameters and
individual behaviour concomitantly over the long-term to better characterize
optimal environmental conditions and potential resilience of wildlife. Such an
approach is crucial if we want to anticipate the effects of environmental change
on Antarctic penguin populations.
PMID- 29957837
TI - Artemether for topical use in patients with seborrhoeic keratosis.
PMID- 29957838
TI - Osteoporotic Vertebral Fracture Prevalence Varies Widely: Reply Letter to the
Editor.
PMID- 29957839
TI - Physical properties of the photodamaged human skin dermis: Rougher collagen
surface and stiffer/harder mechanical properties.
AB - Fragmentation of collagen fibrils and aberrant elastic material (solar elastosis)
in the dermal extracellular matrix (ECM) is among the most prominent features of
photodamaged human skin. These alterations impair the structural integrity and
create a dermal microenvironment prone to skin disorders. The objective of this
study was to determine the physical properties (surface roughness, stiffness and
hardness) of the dermal ECM in photodamaged and subject-matched sun-protected
human skin. Skin samples were sectioned and analysed by histology, atomic force
microscopy and nanoindentation. Dermal ECM collagen fibrils were more
disorganized (ie, rougher surface), and the dermal ECM was stiffer and harder, in
photodamaged forearm, compared to sun-protected underarm skin. Cleavage of
collagen fibrils in sun-protected underarm dermis by recombinant human matrix
metalloproteinase-1 resulted in rougher collagen fibril surface and reduced
dermal stiffness and hardness. Degradation of elastotic material in photodamaged
skin by treatment with purified neutrophil elastase reduced stiffness and
hardness, without altering collagen fibril surface roughness. Additionally,
expression of two members of the lysyl oxidase gene family, which insert cross
links that stiffen and harden collagen fibrils, was elevated in photodamaged
forearm dermis. These data elucidate the contributions of fragmented collagen
fibrils, solar elastosis and elevated collagen cross-linking to the physical
properties of the dermal ECM in photodamaged human skin. This new knowledge
extends current understanding of the impact of photodamage on the dermal ECM
microenvironment.
PMID- 29957840
TI - Risk factors associated with invasive orthopaedic interventions in males with
haemophilia enrolled in the Universal Data Collection program from 2000 to 2010.
AB - BACKGROUND: Invasive orthopaedic interventions (IOI) are often used to control
recurrent haemarthrosis, pain and loss of joint function, in males with
haemophilia (Factor VIII and Factor IX deficiency). AIM: Identify risk factors
associated with IOIs in males with haemophilia enrolled in the Universal Data
Collection (UDC) surveillance program from 2000 until 2010. METHODS: Data were
collected on IOIs performed on patients receiving care in 130 haemophilia
treatment centers in the United States annually by health care providers using
standardized forms. IOIs included in this study are as follows: 1) synovectomy
and 2) arthrodesis or arthroplasty (A/A). Information about potential risk
factors was obtained from the preceding UDC visit if available, or from the same
visit if not. Patients with no reported IOI at any of their UDC visits were the
reference group for the analysis. Multivariate analyses were conducted to
identify independent risk factors for synovectomies and arthrodesis/arthroplasty.
RESULTS: Risk factors significantly associated with the two IOI categories were
age, student status, haemophilia severity, number of joint bleeds within the last
6 months, HIV or hepatitis C (HCV) status. Multivariate analyses showed patients
on continuous prophylaxis were 50% less likely to have had a synovectomy and were
40% less likely to have an A/A. CONCLUSIONS: This study shows modifiable risk
factors, including management of bleeding episodes with a continuous prophylactic
treatment schedule are associated with a decreased likelihood of IOIs in males
with haemophilia.
PMID- 29957841
TI - beta-elemene increases the sensitivity of gastric cancer cells to TRAIL by
promoting the formation of DISC in lipid rafts.
AB - beta-Elemene, an anti-cancer drug extracted from traditional Chinese medicinal
herb, showed anti-tumor effects on gastric cancer cells. Our previous studies
reported gastric cancer cells are insensitive to TRAIL. However, whether beta
elemene could enhance anti-cancer effects of TRAIL on gastric cancer cells is
unknown. In our present study, beta-elemene prevented gastric cancer cell
viability in dose-dependent manner, and when combined with TRAIL, obviously
inhibited proliferation and promoted apoptosis in gastric cancer cells. Compared
to beta-elemene or TRAIL alone, treatment with beta-elemene and TRAIL obviously
promoted DR5 clustering as well as translocation of Caspase-8, DR5 and FADD into
lipid rafts. This led to cleavage of Caspase-8 and the formation of death
inducing signaling complex (DISC) in lipid rafts. The cholesterol-sequestering
agent nystatin partially reversed DR5 clustering and DISC formation, preventing
apoptosis triggered by the combination of beta-elemene and TRAIL. Our results
suggest that beta-elemene increases the sensitivity of gastric cancer cells to
TRAIL partially by promoting the formation of DISC in lipid rafts.
PMID- 29957842
TI - Regional Patterns of Alcohol-Induced Neuronal Loss Depend on Genetics:
Implications for Fetal Alcohol Spectrum Disorder.
AB - BACKGROUND: Alcohol exposure during pregnancy can kill developing neurons and
lead to fetal alcohol spectrum disorder (FASD). However, affected individuals
differ in their regional patterns of alcohol-induced neuropathology. Because
neuroprotective genes are expressed in spatially selective ways, their mutation
could increase the vulnerability of some brain regions, but not others, to
alcohol teratogenicity. The objective of this study was to determine whether a
null mutation of neuronal nitric oxide synthase (nNOS) can increase the
vulnerability of some brain regions, but not others, to alcohol-induced neuronal
losses. METHODS: Immunohistochemistry identified brain regions in which nNOS is
present or absent throughout postnatal development. Mice genetically deficient
for nNOS (nNOS-/- ) and wild-type controls received alcohol (0.0, 2.2, or 4.4
mg/g/d) over postnatal days (PD) 4 to 9. Mice were sacrificed in adulthood (~PD
115), and surviving neurons in the olfactory bulb granular layer and brain stem
facial nucleus were quantified stereologically. RESULTS: nNOS was expressed
throughout postnatal development in olfactory bulb granule cells but was never
expressed in the facial nucleus. In wild-type mice, alcohol reduced neuronal
survival to similar degrees in both cell populations. However, null mutation of
nNOS more than doubled alcohol-induced cell death in the olfactory bulb granule
cells, while the mutation had no effect on the facial nucleus neurons. As a
result, in nNOS-/- mice, alcohol caused substantially more cell loss in the
olfactory bulb than in the facial nucleus. CONCLUSIONS: Mutation of the nNOS gene
substantially increases vulnerability to alcohol-induced cell loss in a brain
region where the gene is expressed (olfactory bulb), but not in a separate brain
region, where the gene is not expressed (facial nucleus). Thus, differences in
genotype may explain why some individuals are vulnerable to FASD, while others
are not, and may determine the specific patterns of neuropathology in children
with FASD.
PMID- 29957843
TI - Nanoquencher-Based Selective Imaging of Protein Glutathionylation in Live
Mammalian Cells.
AB - Changes in the cellular levels of glutathione (GSH) and protein S
glutathionylation (PSSG) are closely associated with a number of human diseases.
Despite recent advances, few thiol-reactive, small-molecule GSH sensors could
selectively detect GSH over other endogenous thiols, and none was capable of
detecting PSSG in live mammalian cells. By using a dye-loaded mesoporous silica
nanoquencher (qMSN) capped with anti-GSH antibody capable of highly selective
binding toward GSH and glutathionylated proteins over other molecules, we have
successfully developed a fluorescence GSH/PSSG nanosensor, which showed
unprecedented selectivity toward PSSG even in the presence of GSH, had
amplifiable and programmable fluorescence Turn-ON properties, and could be used
to image endogenous PSSG in live mammalian cells under stimulated conditions for
the first time.
PMID- 29957844
TI - Role of Nutrition Support in Inflammatory Conditions.
AB - This review intends to summarize recent development on the potential nutrition
implications of acute inflammation encountered during critical illness. Different
aspects of the inflammatory response and their impact on nutrition management
during critical illness will be discussed: the timing of the postinjury metabolic
response, the integration of regulatory mechanisms involved in the metabolic
response to stress, the oxidative stress, the metabolic and clinical consequences
in terms of energy expenditure, use of energy, changes in body composition, and
behavior.
PMID- 29957845
TI - Stereodivergent Alkyne Reduction by using Water as the Hydrogen Source.
AB - A homogeneous Pd-catalyzed stereodivergent reduction of alkynes to Z and E
alkenes by using H2 O as the H2 source is presented. Mediated by a diboron
reagent, the transfer hydrogenation has been accomplished to yield the desired
geometrical isomer by rational ligand selection. The switchable stereoselectivity
achieved using simple phosphine ligands is generally excellent. D2 O has also
been used as a D2 source for synthesizing the corresponding deuterated olefins.
Supported by a gram-scale synthesis, the reaction can easily be scaled up making
it an efficient way to prepare alkenes commercially as well. Mechanistic studies
suggest formation of H-PdL2 -OAc as the crucial step leading to the presence of
two pathways involving H-Pd-B(OR)2 and molecular H2 as active intermediates.
PMID- 29957846
TI - Prediction of individual factor VIII or IX level for the correction of thrombin
generation in haemophilic patients.
AB - BACKGROUND: The thrombin generation (TG) assay can assess individual clotting
potential. The thrombin generation potential is correlated with the patient's
bleeding phenotype and varies from one patient to the other for the same degree
of factor VIII or IX deficiency. OBJECTIVE: To define in vitro for individual
haemophilic patients the target factor VIII or IX level required to normalize
their TG. PATIENTS/METHODS: Plasmas from 20 haemophilic patients were spiked with
increasing levels of the deficient coagulation factor and TG parameters were
measured. The relationships between factor levels and TG parameters were
determined by linear regression. The normal range of thrombin generation was
defined in 39 healthy male volunteers. RESULTS: Despite inter-individual
heterogeneity in basal TG and responses to spiking, a linear relationship was
found between factor VIII or IX levels and TG parameters for individual patients.
Based on the individual responses of patient plasmas to spiking, it is possible
to define in vitro the target factor VIII or IX levels needed to normalize the TG
parameters. For both haemophilic A and haemophilic B patients, significant
correlations were found between basal peak values and their correction slopes.
The correction slope was steeper in haemophilic B patients, so the factor IX
level needed to normalize the TG parameters was lower than for haemophilic A
patients. CONCLUSIONS: The TG assay could be used to determine in vitro the
patient-specific factor VIII or IX level to be reached to effectively normalize
their TG. These in vitro results should be confirmed by ex-vivo studies.
PMID- 29957848
TI - DREADD to the Core. Commentary on Purohit et al. (2018): Pharmacogenetic
Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice.
PMID- 29957847
TI - Investigation of potential toxic components based on the identification of Genkwa
Flos chemical constituents and their metabolites by high-performance liquid
chromatography coupled with a Q Exactive high-resolution benchtop quadrupole
Orbitrap mass spectrometer.
AB - Genkwa Flos, a famous traditional Chinese medicine has been reported to have
significant hepatotoxicity. A high-throughput and reliable method was established
to explore potential toxic components by high-performance liquid chromatography
coupled with a Q Exactive high-performance benchtop quadrupole-Orbitrap mass
spectrometer. A total of 68 compounds including 22 chemical components and 46
metabolites were tentatively identified based on the accurately measured mass
value, retention time, and fragmentation pattern. Besides, the metabolic pathways
of main components in Genkwa Flos were also illustrated. The results indicated
that hydroxylation, demethylation, methylation, glucuronidation, sulfation,
cysteine conjugation, and glutathione conjugation participated in the metabolic
reactions of Genkwa Flos. Moreover, 12 Genkwa Flos chemical components and 26
metabolites were detected in cell lysate, which were considered as the bound
components to HL-7702 cells. In view of cell affinity theory, these compounds
were preliminarily deduced to be potential toxic ingredients for the
hepatotoxicity induced by Genkwa Flos. The results demonstrated that the
developed method was a very feasible and efficient approach for the components
identification even in the complex matrix. In conclusion, this study will provide
a deep insight into the toxic substances of Genkwa Flos and lay a chemical basis
for in-depth toxic studies on Genkwa Flos hepatotoxicity.
PMID- 29957849
TI - Silicon Oxide (SiOx ): A Promising Material for Resistance Switching?
AB - Interest in resistance switching is currently growing apace. The promise of novel
high-density, low-power, high-speed nonvolatile memory devices is appealing
enough, but beyond that there are exciting future possibilities for applications
in hardware acceleration for machine learning and artificial intelligence, and
for neuromorphic computing. A very wide range of material systems exhibit
resistance switching, a number of which-primarily transition metal oxides-are
currently being investigated as complementary metal-oxide-semiconductor (CMOS)
compatible technologies. Here, the case is made for silicon oxide, perhaps the
most CMOS-compatible dielectric, yet one that has had comparatively little
attention as a resistance-switching material. Herein, a taxonomy of switching
mechanisms in silicon oxide is presented, and the current state of the art in
modeling, understanding fundamental switching mechanisms, and exciting device
applications is summarized. In conclusion, silicon oxide is an excellent choice
for resistance-switching technologies, offering a number of compelling advantages
over competing material systems.
PMID- 29957850
TI - Tactics for Teaching Evidence-Based Practice: Video as a Support for Learning
International Database Searching in Nursing Education.
PMID- 29957851
TI - In vitro models of dermatophyte infection to investigate epidermal barrier
alterations.
AB - Fungal infections of the skin, known as dermatophytoses, are initiated at the
epidermal barrier and lead to dysfunctions of the stratum corneum and cornified
skin appendages. Dermatophytosis affects a significant part of the human
population and, despite the availability of effective treatments, its prevalence
is still increasing. Numerous dermatophyte species are able to induce lesions in
both animals and humans, with different clinical pictures and host inflammatory
responses. The understanding of the infectious process and of tissue responses
has been impeded by discrepancies between observations in vivo or in research
models. Indeed, cells cultured as monolayers do not undergo the keratinization
process required to study the adherence and invasion of dermatophytes. Animal
models lack relevance to study human dermatophytosis because of species-specific
differences in the development of lesions and inflammatory responses. This review
focuses on the recent development of cultured human skin equivalents, which
partly overcomes those limitations and allows improved understanding of the
pathogenesis of dermatophytosis in human being, especially the impacts of
infection on epidermal barrier integrity.
PMID- 29957852
TI - Peripatric speciation associated with genome expansion and female-biased sex
ratios in the moss genus Ceratodon.
AB - PREMISE OF THE STUDY: A period of allopatry is widely believed to be essential
for the evolution of reproductive isolation. However, strict allopatry may be
difficult to achieve in some cosmopolitan, spore-dispersed groups, like mosses.
We examined the genetic and genome size diversity in Mediterranean populations of
the moss Ceratodon purpureus s.l. to evaluate the role of allopatry and ploidy
change in population divergence. METHODS: We sampled populations of the genus
Ceratodon from mountainous areas and lowlands of the Mediterranean region, and
from Western and Central Europe. We performed phylogenetic and coalescent
analyses on sequences from five nuclear introns and a chloroplast locus to
reconstruct their evolutionary history. We also estimated genome size using flow
cytometry (employing propidium iodide) and determined the sex of samples using a
sex-linked PCR marker. KEY RESULTS: Two well-differentiated clades were resolved,
discriminating two homogeneous groups: the widespread C. purpureus and a local
group mostly restricted to the mountains in Southern Spain. The latter also
possessed a genome size 25% larger than the widespread C. purpureus, and the
samples of this group consist entirely of females. We also found hybrids, and
some of them had a genome size equivalent to the sum of the C. purpureus and
Spanish genome, suggesting that they arose by allopolyploidy. CONCLUSIONS: These
data suggest that a new species of Ceratodon arose via peripatric speciation,
potentially involving a genome size change and a strong female-biased sex ratio.
The new species has hybridized in the past with C. purpureus.
PMID- 29957853
TI - Superflexible Multifunctional Polyvinylpolydimethylsiloxane-Based Aerogels as
Efficient Absorbents, Thermal Superinsulators, and Strain Sensors.
AB - Aerogels are porous materials but show poor mechanical properties and limited
functionality, which significantly restrict their practical applications.
Preparation of highly bendable and processable aerogels with multifunctionality
remains a challenge. Herein we report unprecedented superflexible aerogels based
on polyvinylpolydimethylsiloxane (PVPDMS) networks,
PVPDMS/polyvinylpolymethylsiloxane (PVPMS) copolymer networks, and
PVPDMS/PVPMS/graphene nanocomposites by a facile radical
polymerization/hydrolytic polycondensation strategy and ambient pressure drying
or freeze drying. The aerogels have a doubly cross-linked organic-inorganic
network structure consisting of flexible polydimethylsiloxanes and hydrocarbon
chains with tunable cross-linking density, tunable pore size and bulk density.
They have a high hydrophobicity and superflexibility and combine selective
absorption, efficient separation of oil and water, thermal superinsulation, and
strain sensing.
PMID- 29957854
TI - Similar controls on calcification under ocean acidification across unrelated
coral reef taxa.
AB - Ocean acidification (OA) is a major threat to marine ecosystems, particularly
coral reefs which are heavily reliant on calcareous species. OA decreases
seawater pH and calcium carbonate saturation state (Omega), and increases the
concentration of dissolved inorganic carbon (DIC). Intense scientific effort has
attempted to determine the mechanisms via which ocean acidification (OA)
influences calcification, led by early hypotheses that calcium carbonate
saturation state (Omega) is the main driver. We grew corals and coralline algae
for 8-21 weeks, under treatments where the seawater parameters Omega, pH, and DIC
were manipulated to examine their differential effects on calcification rates and
calcifying fluid chemistry (Omegacf , pHcf , and DICcf ). Here, using long
duration experiments, we provide geochemical evidence that differing
physiological controls on carbonate chemistry at the site of calcification,
rather than seawater Omega, are the main determinants of calcification. We found
that changes in seawater pH and DIC rather than Omega had the greatest effects on
calcification and calcifying fluid chemistry, though the effects of seawater
carbonate chemistry were limited. Our results demonstrate the capacity of
organisms from taxa with vastly different calcification mechanisms to regulate
their internal chemistry under extreme chemical conditions. These findings
provide an explanation for the resistance of some species to OA, while also
demonstrating how changes in seawater DIC and pH under OA influence calcification
of key coral reef taxa.
PMID- 29957855
TI - The USP8 mutational status may predict long-term remission in patients with
Cushing's disease.
AB - OBJECTIVE: Almost half of the cases of Cushing's disease (CD) tumours carry
recurrent activating somatic mutations in the ubiquitin-specific protease eight
gene (USP8). The USP8 mutational status could predict remission in patients with
CD, so our objective was to correlate the presence of somatic USP8 mutations with
the rate of recurrence after transsphenoidal surgery (TSS) retrospectively.
DESIGN: Biochemical, radiological and clinical data were retrospectively assessed
in 48 patients. USP8 mutational status was determined from corticotroph tumour
samples. Association between USP8 mutational status, remission and recurrence was
investigated. PATIENTS: Patients with Cushing's disease from a single-centre
cohort who underwent TSS between 1991 and 2012. MEASUREMENTS: Long-term remission
and recurrence rate after TSS with at least 6 months follow-up. Biochemical,
radiological and clinical data, including sex, age at diagnosis, tumour size and
pre-operative hormonal levels. USP8 mutational status. RESULTS: Patients with
USP8 mutant corticotroph tumours (18 of 48; 37%) were diagnosed significantly
earlier (mean +/- SD 46 +/- 10 years vs 53 +/- 11 years; P = 0.028) and presented
with higher pre-operative 24-hour urinary-free cortisol levels (median IQR MUg/24
hours 1174.0, 1184.5 vs 480.0, 405.3; P = 0.045). The incidence of recurrence in
a 10-year follow-up was significantly higher in patients with USP8 mutant tumours
after the initial remission (58% vs 18% P = 0.026). Recurrence appeared
significantly earlier in these patients (months 70, 44-97 95% CI vs 102, 86-119
95% CI; P = 0.019). CONCLUSION: Recurrence appears to be more frequent and
earlier after TSS in patients with USP8 mutant corticotroph tumours.
PMID- 29957856
TI - Testing the Dutilleul syndrome: host use drives the convergent evolution of
multiple traits in parasitic wasps.
AB - Common life-history aspects among independent lineages often result in the
repeated evolution of suites of adaptive traits, or 'syndromes'. Such syndromes
can be key avenues to understand relationships between morphological and
ecological traits, but are rarely tested due to insufficient trait shift
repetitions. We use a hyperdiverse lineage to investigate the evolution of a
syndrome. Cryptine ichneumonid wasps that parasitize insects concealed in hard
substrates display several traits that are putative adaptations to that end.
Using a phylogenetic framework from a combined multigene molecular and
morphological data set with 308 cryptine species, we tested whether these traits
were part of a morphofunctional syndrome related to host use. Ancestral state
estimations show multiple origins for six investigated traits, which are
correlated to each other and to the use of deeply concealed hosts, suggesting
adaptation. Putatively adaptive traits showed a much stronger link among
themselves than with an assemblage of 49 other morphological traits. However,
estimation of the order of evolution in adaptive traits showed no structured
pattern. The results indicate that the challenge of attacking deeply concealed
hosts induced the repeated evolution of a 'Dutilleul syndrome', named after the
'walker-through-walls' character from French literature. They also point towards
a dynamic scenario in the evolution of complex functional systems. These findings
highlight the power of morphology to illuminate poorly known aspects of natural
history, and how hyperdiverse lineages can be used to understand the evolution of
complex traits.
PMID- 29957857
TI - Incidence of obstructive sleep apnoea in patients with hidradenitis suppurativa:
a retrospective population-based cohort analysis.
PMID- 29957858
TI - Osteoporotic Vertebral Fracture Prevalence Varies Widely.
PMID- 29957859
TI - Isolation of Human Innate Lymphoid Cells.
AB - Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have
important effector and regulatory functions in the first line of defense against
pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their
function mirrors T helper cells and cytotoxic CD8+ T lymphocytes, but they lack
expression of rearranged antigen-specific receptors. Distinct ILC subsets are
classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s
and lymphoid tissue-inducer cells), based on the expression of transcription
factors and the cytokines they produce. As the frequency of ILCs is low, their
isolation requires extensive depletion of other cell types. The lack of unique
cell surface antigens further complicates the identification of these cells.
Here, methods for ILC isolation and characterization from human peripheral blood
and different tissues are described. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29957860
TI - Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and
Women's Health 2017 guidelines for hormone replacement therapy.
AB - Hormone replacement therapy (HRT) plays a large part in maintaining and improving
the quality of life (QOL) of postmenopausal women. Despite this obvious role, the
use of HRT has stagnated in Japan as well as the United States, since the interim
report of the HRT trial of Women's Health Initiative study was published in 2002.
The Japan Society of Obstetrics and Gynecology and Japan Society for Menopause
and Women's Health formulated the Guidelines for Hormone Replacement Therapy in
2009, which was subsequently revised in 2012, with the aim of organizing
perceptions about HRT and allowing people to provide or receive HRT with a sense
of security. Later on, in light of changes in indications for HRT and attitudes
toward its impact on cancer risks, amendments were made again in 2017. With the
establishment of the 2017 guidelines, practitioners in Japan are able to address
various issues related to HRT with more appropriate judgment. Moreover, the
practice of reliable, safe and effective HRT is expected to promote further
efforts toward improvement or maintenance of QOL in patients.
PMID- 29957861
TI - HPV vaccination: balancing facts.
PMID- 29957862
TI - Genotype-phenotype data from a case series of patients with mosaic
neurofibromatosis type 1.
PMID- 29957863
TI - Preliminary experience of sequential use of normothermic and hypothermic
oxygenated perfusion for donation after circulatory death kidney with warm
ischemia time over the conventional criteria - a retrospective and observational
study.
AB - Donation after circulatory death (DCD) is a potential source of reducing organ
demand. In Italy, DCD requires a 20-min no-touch period that prolongs warm
ischemia and increases delayed graft function (DGF) risk and graft loss. We
report here our preliminary experience of sequential use of normothermic regional
perfusion (NRP), as standard procedure, and hypothermic oxygenated perfusion
(HOPE), as an experimental technique of organ preservation, in 10 kidney
transplants (KT) from five DCD Maastricht III with extensive functional warm
ischemia time (fWIT) up to 325 min. During NRP, renal function tests were
evaluated to accept organs which were retrieved according to standard fashion
with biopsy. While waiting for pathology and cross-match results, organs were
preserved with HOPE through pressure- and temperature-controlled arterial
pulsatile flow. All grafts with Karpinski score <=4 were used for conventional
single KT with mean cold ischemia time of 584 +/- 167 min and mean fWIT of 151 +/
132 min. At the end of HOPE, lactate levels increased significantly in all cases
with DGF (P = 0.0095), which were 3/10 (30%). No primary nonfunctions were
recorded, and all patients had sCr < 1.5 mg/dl at 6-month post-KT. NRP and HOPE
for DCD may overcome fWIT limits safely, and lactate during HOPE predicts DGF.
PMID- 29957864
TI - The impact of a malignant diagnosis on the pattern and outcome of readmission
after liver and pancreatic surgery: An analysis of the nationwide readmissions
database.
AB - BACKGROUND AND OBJECTIVES: Reducing readmissions is an important quality
improvement metric. We sought to investigate patterns of 90-day readmission after
hepato-pancreatic (HP) procedures. METHODS: The Nationwide Readmissions Database
(NRD) was used to identify patients undergoing HP procedures between 2010 and
2014. Patients were stratified according to benign versus malignant HP diagnoses
and as index (same hospital as operation) versus non-index (different hospital)
readmissions. RESULTS: Among the 41 059 patients who underwent HP procedures, 26
563 (65%) underwent a liver resection while 14 496 (35%) pancreatic resection.
Among all patients, 11 902 (29%) had a benign diagnosis versus 29 157 (71%) who
had a cancer diagnosis. Overall 90-day readmission was 22% (n = 8 998) with a
slight increase in readmissions among patients with a malignant (n = 6 655;23%)
versus benign (n = 2 343;20%) diagnosis (P < 0.001). Readmission to an index
hospital was more common (n = 7 316 81%) versus a non-index hospital (n = 1 682
19%). Non-index hospital readmissions were more frequent among patients with
malignant HP diagnoses (OR, 1.41;P = 0.001). CONCLUSIONS: Up to one in four
patients were readmitted after HP surgery. Late readmission was more common among
patients with a cancer-diagnosis. While most readmissions occurred at the index
hospital, 19% of all readmissions occurred at a non-index hospital and were more
frequent among patients with malignant diagnoses.
PMID- 29957866
TI - Musculoskeletal Pain and Headache in the Active Duty Military Population: An
Integrative Review.
AB - BACKGROUND: Since 2001, the U.S. Armed Forces' training and deployment have
greatly increased, escalating the risk of injury and pain-related issues both at
home station and deployment environments. AIMS: This integrative review examines
the incidence, prevalence, and risk factors for musculoskeletal pain (MSP) and
headaches in active duty (AD) military populations. METHODS: Peer-reviewed
research published between 2001 and 2016 was identified relevant to MSP and
headache in AD military personnel using MeSH terms in key biomedical databases.
Inclusion criteria were: epidemiological studies examining MSP or headache as
primary or secondary outcome; samples that included AD populations; and studies
conducted in the theater of operations, at home station, and in military
treatment or Veterans Health Administration facilities. RESULTS: Twenty-six
articles met inclusion criteria. Low back pain (LBP) was the most prevalent MSP
diagnosis. The incidence of LBP was 40.5 per 1,000 person-years and was
comparable to nonmilitary populations. Inflammation and pain from overuse
comprised the largest proportion of injury mechanism, accounting for about 82% of
all injuries among nondeployed military personnel. The risk of MSP was greater
for AD, female, Army, enlisted personnel, and those with greater time in a motor
vehicle. Evidence suggests posttraumatic headache, occurring in up to 92% of
military personnel who have sustained a mild traumatic brain injury, is
associated with chronic daily headaches. IMPLICATIONS: Nurses must recognize the
consequences military service can have on the development of pain. Nurses have an
opportunity to positively impact the health and well-being of military and
veteran populations through early recognition and treatment of pain. LINKING
EVIDENCE TO ACTION: The findings from this review underscore considerable
magnitude of MSP in military personnel and expose modifiable risk factors and
potential targets for designing nurse-led interventions to improve pain and
symptoms in military subpopulations.
PMID- 29957867
TI - Construction of low contracted 3D skin equivalents by genipin cross-linking.
AB - Continuous contraction of 3D skin equivalents in construction and use restricts
their applications in clinical and pharmaceutical practices. So far, no effective
method has been developed to inhibit such contraction. Hence, low cytotoxic cross
linkers, 1-ethyl-3-3-dimethylaminopropylcarbodiimide hydrochloride (EDC) and
genipin, are investigated to reduce the contraction in this study. As found, both
genipin and EDC at 0.2 and 0.4 mmol/L are nontoxic to collagen-entrapped
fibroblasts and upregulate the extracellular matrix expression of fibroblasts in
cross-linked collagen. Particularly, collagen cross-linking by intermediate
concentrations of genipin, specifically 0.4 mmol/L, greatly reduces the
contraction of 3D skin equivalents from 87% to 28% (n = 9, P < 0.05), while the
collagen after EDC cross-linking at 0.4 mmol/L still presented severe contraction
of 64% over a 21-day follow-up period. The inhibited contraction might relate to
the increased gel stiffness and slowed collagen degradation. Moreover, the
genipin cross-linking does not impair the formation of epidermal layers and
improves the epidermal-dermal junction of skin equivalents as well. In this
regard, genipin cross-linking might facilitate the applications of 3D skin
equivalents in clinical practices and pharmacology testing.
PMID- 29957865
TI - R-High-CHOP/CHASER/LEED with autologous stem cell transplantation in newly
diagnosed mantle cell lymphoma: JCOG0406 STUDY.
AB - Although induction immunochemotherapy including high-dose cytarabine and
rituximab followed by high-dose chemotherapy (HDC) with autologous stem cell
transplantation (ASCT) is recommended for younger patients (<=65 years old) with
untreated mantle cell lymphoma (MCL), no standard induction and HDC regimen has
been established. We conducted a phase II study of induction immunochemotherapy
of R-High-CHOP/CHASER followed by HDC of LEED with ASCT in younger patients with
untreated advanced MCL. Eligibility criteria included untreated MCL, stage II
bulky to IV, and age 20-65 years. Patients received 1 cycle of R-High-CHOP
followed by 3 cycles of CHASER every 3 weeks. Peripheral blood stem cells (PBSC)
were harvested during CHASER. LEED with ASCT was delivered to patients who
responded to R-High-CHOP/CHASER. Primary endpoint was 2-year progression-free
survival (PFS). From June 2008 to June 2012, 45 patients (median age 59 years;
range 38-65 years) were enrolled. PBSC were successfully harvested from 36 of 43
patients. Thirty-five patients completed ASCT. Two-year PFS was 77% (80% CI 68
84), which met the primary endpoint. Five-year PFS and overall survival were 52%
(95% CI 34-68%) and 71% (95% CI 51-84%), respectively. Overall response and
complete response rates after induction immunochemotherapy were 96% and 82%,
respectively. The most common grade 4 toxicities were hematological. In younger
patients with untreated MCL, R-High-CHOP/CHASER/LEED with ASCT showed high
efficacy and acceptable toxicity, and it can now be considered a standard
treatment option.
PMID- 29957868
TI - Nutrition Adequacy Therapeutic Enhancement in the Critically Ill: A Randomized
Double-Blind, Placebo-Controlled Trial of the Motilin Receptor Agonist Camicinal
(GSK962040): The NUTRIATE Study.
AB - BACKGROUND: Camicinal is a novel, nonmacrolide, motilin receptor agonist that
accelerates gastric emptying in critically ill patients with established feed
intolerance. The primary question was whether the preemptive administration of
camicinal increased the provision of enteral nutrition (EN) to critically ill
patients with risk factors that predisposed to feed intolerance. METHODS: This
was an international, multicenter, parallel-group, blinded, randomized controlled
trial. Patients at risk for feed intolerance, defined as receiving moderate to
high doses of vasopressors or opiates, or admitted because of multiple traumatic
injuries or with brain injury, received either enteral camicinal 50 mg or placebo
daily for a maximum of 7 days, along with EN administered according to a
standardized feeding protocol. The primary outcome was the daily adequacy of
enteral feed delivered, as assessed by percentage of goal volume
(delivered/prescribed * 100) before development of intolerance. RESULTS: Eighty
four patients participated. The administration of camicinal did not result in a
statistically significant clinical difference in the daily average percentage
goal volume delivered (camicinal vs placebo: 77% [95% confidence interval: 71,
83] vs 68% (58, 78); mean difference 9% [-5, 23]; P = 0.21). Similarly, there
were no differences in the percentage goal calories (76% [65, 88] vs 68% [60,
77]) and protein (76% [66, 86] vs 70% [61, 80]) administered, or the incidence of
feed intolerance (15% vs 14%). CONCLUSION: The incidence of feed intolerance was
low in both groups. In this cohort the preemptive administration of enteral
camicinal did not significantly augment the provision of goal EN.
PMID- 29957869
TI - A Transferrin Triggered Pathway for Highly Targeted Delivery of Graphene-Based
Nanodrugs to Treat Choroidal Melanoma.
AB - The synthesis of transferrin (Tf)-modified pegylated graphene (PG) and its
application as a highly efficient drug delivery carrier for therapy of Ocular
Choroidal Melanoma-1 (OCM-1) cells is presented. For the first reported time,
nanoscaled PG is prepared using an environmentally friendly ball-milling
technique. The unique 2D nanostructure obtained using this PG synthesis approach
offers considerable advantages in terms of drug loading and delivery, as well as
the conjugation of Tf to PG providing a more targeted delivery vehicle. A highly
efficient targeted pathway toward OCM-1 cells triggered by an affinity between Tf
and Tf receptors expressed on the surface of OCM-1 cells is reported first here.
PG-Tf is observed to easily anchor anticancer drugs such as doxorubicin via pi-pi
stacking. This work performs a Transwell two cells coculture experiment, a 3D in
vitro tumor model, and an in vivo mouse model with OCM-1 tumors to demonstrate
the composite's therapeutic superiority over conventional systems for the
targeted delivery and controlled release of antitumor drugs.
PMID- 29957871
TI - Threshold-stimulated kallikrein activity distinguishes bradykinin- from histamine
mediated angioedema.
AB - BACKGROUND: The lack of specific biomarkers makes the diagnosis of hereditary
angioedema (HAE) with normal levels of C1-inhibitor (C1INH) protein (HAE-nl
C1INH) and idiopathic non-histaminergic angioedema (INHA) difficult. Confirming
or excluding these diagnoses is a significant challenge for clinicians evaluating
patients with angioedema. OBJECTIVE: To develop a reliable biomarker that would
aid the diagnosis of HAE-nl-C1INH and INHA. METHODS: A total of 154 consecutive
patients referred for angioedema at a single centre were enrolled and evaluated.
Subjects were clinically phenotyped based on clinical history and response to
treatment by clinicians blinded to laboratory assay results. Plasma kallikrein
activity was measured by the cleavage of the fluorometric substrate Z-Phe-Arg-AMC
HCL in plasma samples stimulated ex vivo with submaximal doses of dextran
sulphate. RESULTS: Stimulated plasma kallikrein activity (mean relative
fluorescence units/min +/- SD) was significantly increased in both HAE-nl-C1INH
(1804 +/- 600) and INHA (1579 +/- 371) subjects compared to non-swelling controls
(171 +/- 46) and histaminergic angioedema (133 +/- 30) subjects. Using a
threshold cut-off based on the normal controls, HAE-nl-C1INH and INHA subjects
could be differentiated from histaminergic angioedema subjects with high
sensitivity (negative predictive value 86%-89%) and specificity (positive
predictive value 80%-100%). CONCLUSION AND CLINICAL RELEVANCE: The stimulated
kallikrein activity assay allows differentiation of bradykinin- from histamine
mediated angioedema. The assay could feasibly be considered as a potential
clinical tool for the diagnosis of bradykinin-mediated angioedema.
PMID- 29957870
TI - The Impact of Alcohol Use on Frontal White Matter in HIV.
AB - BACKGROUND: Alcohol use disorder (AUD) is prevalent among individuals diagnosed
with human immunodeficiency virus (HIV), and both HIV and alcohol use have been
shown to negatively affect the integrity of white matter pathways in the brain.
Behavioral, functional, and anatomical impairments have been linked independently
to HIV and alcohol use, and these impairments have bases in specific frontally
mediated pathways within the brain. METHODS: Magnetic resonance imaging data were
acquired for 37 HIV+ participants without dementia or hepatitis C. Imaging data
were processed through the FreeSurfer and TraCULA pipelines to obtain 4 bilateral
frontal white matter tracts for each participant. Diffusion metrics of white
matter integrity along the highest probability pathway for each tract were
analyzed with respect to demographics, disease-specific variables, and reported
substance use. RESULTS: Significantly increased axial diffusivity (decreased
axonal integrity) and a trending increase in mean diffusivity were observed along
the anterior thalamic radiation (ATR) in participants with a history of AUD. A
diagnosis of AUD explained over 36% of the variance in diffusivity along the ATR
overall when accounting for clinical variables including nadir CD4 and age
adjusted HIV infection length. CONCLUSIONS: This study provides evidence of HIV
related associations between alcohol use and indicators of axonal integrity loss
along the ATR, a frontal pathway involved in the inhibition of addictive or
unwanted behaviors. Reduced axonal integrity of this pathway was greatest in HIV+
participants with an AUD, even when considering the effect of age-adjusted
disease length and severity (nadir CD4). This finding implicates a potential
biological mechanism linking reduced integrity of frontal white matter to the
high prevalence of AUD in an HIV+ population without dementia or hepatitis C.
PMID- 29957872
TI - Defective Anatase TiO2-x Mesocrystal Growth In Situ on g-C3 N4 Nanosheets:
Construction of 3D/2D Z-Scheme Heterostructures for Highly Efficient Visible
Light Photocatalysis.
AB - Environmental remediation by employing visible-light-active semiconductor
heterostructures provides effective solutions for handling emerging contaminants
by a much greener and lower cost approach compared with other methods. This
report demonstrates that the in situ growth of nanosized single-crystal-like
defective anatase TiO2-x mesocrystals (DTMCs) on g-C3 N4 nanosheets (NSs) can
produce a 3D/2D DTMC/g-C3 N4 NS heterostructure with the two components held
together by chemical bonds to form tight interfaces. This nanostructured
heterostructure displayed remarkably improved photocatalytic activity toward the
removal of the model pollutants Methyl Orange (MO) and CrVI under visible-light
irradiation in comparison with the pristine DTMC and g-C3 N4 NS components, which
suggests that both the oxidation and reduction abilities of the DTMC/g-C3 N4 NSs
were simultaneously enhanced after fabrication. On the basis of the results of a
systematic characterization, a reasonable mechanism for the photocatalytic
activity based on a direct Z-scheme heterojunction is proposed and further
verified by the measurement of . OH. This novel Z-scheme heterojunction endows
the heterostructure with improved photogenerated electron/hole pair separation
and a strong redox ability for the efficient degradation of wastewater
pollutants. This work will be useful for the design and fabrication of direct Z
scheme heterostructured photocatalysts with novel architectures for applications
in energy conversion and environmental remediation.
PMID- 29957873
TI - High Cell Density Perfusion Culture has a Maintained Exoproteome and Metabolome.
AB - The optimization of bioprocesses for biopharmaceutical manufacturing by Chinese
hamster ovary (CHO) cells can be a challenging endeavor and, today, heavily
relies on empirical methods treating the bioreactor process and the cells as
black boxes. Multi-omics approaches have the potential to reveal otherwise
unknown characteristics of these systems and identify culture parameters to more
rationally optimize the cultivation process. Here, the authors have applied both
metabolomic and proteomic profiling to a perfusion process, using CHO cells for
antibody production, to explore how cell biology and reactor environment change
as the cell density reaches >=200 * 106 cells mL-1 . The extracellular metabolic
composition obtained in perfusion mode shows a markedly more stable profile in
comparison to fed-batch, despite a far larger range of viable cell densities in
perfusion. This stable profile is confirmed in the extracellular proteosome.
Furthermore, the proteomics data shows an increase of structural proteins as cell
density increases, which could be due to a higher shear stress and explain the
decrease in cell diameter at very high cell densities. Both proteomic and
metabolic results shows signs of oxidative stress and changes in glutathione
metabolism at very high cell densities. The authors suggest the methodology
presented herein to be a powerful tool for optimizing processes of recombinant
protein production.
PMID- 29957875
TI - Ability of women to self-classify into the Robson ten-group classification
system.
AB - OBJECTIVE: Recent guidelines from WHO and the International Federation of
Gynecology and Obstetrics (FIGO) state that the Robson ten-group classification
system (TGCS) should be universally applied to pregnant women. Such information
might enable women to make an informed decision about the place and mode of
delivery. We assessed whether women could self-classify correctly according to
the TGCS. METHODS: A prospective study was conducted in a tertiary level
maternity hospital between March 6 and July 31, 2017. We included post-partum
women admitted to the puerperium ward. Participants were instructed to complete a
multiple-choice questionnaire with a simplified description of TGCS and to
classify themselves into one of the ten groups. A practitioner reclassified women
into the correct TGCS group. Cohen kappa was applied to measure the rate of
agreement between these two evaluations. RESULTS: 400 women were enrolled, with a
global rate of agreement of 81.8% between women's self-evaluation and the
evaluation by the practitioner. A subanalysis showed that the highest rate of
agreement was among the group with higher level education (84.0%). CONCLUSION:
Women of different ages and education backgrounds were able to correctly classify
themselves into the TGCS. The higher the educational level, the greater the rate
of agreement.
PMID- 29957874
TI - GeneExpressScore Signature: a robust prognostic and predictive classifier in
gastric cancer.
AB - Although several prognostic signatures have been developed for gastric cancer
(GC), the utility of these tools is limited in clinical practice due to lack of
validation with large and multiple independent cohorts, or lack of a statistical
test to determine the robustness of the predictive models. Here, a prognostic
signature was constructed using a least absolute shrinkage and selection operator
(LASSO) Cox regression model and a training dataset with 300 GC patients. The
signature was verified in three independent datasets with a total of 658 tumors
across multiplatforms. A nomogram based on the signature was built to predict
disease-free survival (DFS). Based on the LASSO model, we created a
GeneExpressScore signature (GESGC ) classifier comprised of eight mRNA. With this
classifier patients could be divided into two subgroups with distinctive
prognoses [hazard ratio (HR) = 4.00, 95% confidence interval (CI) = 2.41-6.66, P
< 0.0001]. The prognostic value was consistently validated in three independent
datasets. Interestingly, the high-GESGC group was associated with invasion,
microsatellite stable/epithelial-mesenchymal transition (MSS/EMT), and
genomically stable (GS) subtypes. The predictive accuracy of GESGC also
outperformed five previously published signatures. Finally, a well-performed
nomogram integrating the GESGC and four clinicopathological factors was generated
to predict 3- and 5-year DFS. In summary, we describe an eight-mRNA-based
signature, GESGC , as a predictive model for disease progression in GC. The
robustness of this signature was validated across patient series, populations,
and multiplatform datasets.
PMID- 29957876
TI - MicroRNA-34a-5p inhibits liver fibrosis by regulating TGF-beta1/Smad3 pathway in
hepatic stellate cells.
AB - Liver fibrosis is a major cause of morbidity and mortality worldwide, and the
outcome of various chronic liver diseases. Recent studies suggest that aberrant
expression of miR-34 is involved in the progression of various liver diseases
including hepatocellular carcinoma (HCC). However, it is still poorly understood
whether miR-34 mediates the pathogenesis of liver fibrosis. Here, we found that
the expression of microRNA-34a-5p (miR-34a-5p) was significantly decreased in
patients with hepatitis B virus (HBV)-activated liver fibrosis and HCC, as well
as in CC14 (Carbon tetrachloride Tetrachloromethane) induced liver fibrosis model
mice. The TGF-beta1/Smad3 (Transforming growth factor-beta1/Smad3) pathway were
significantly augmented in CC14 induced mice compared with normal control,
whereas inhibitor of TGF-beta1 (SB431542) significantly attenuated liver fibrosis
and TGF-beta1/Smad3 activation. Administration of the miR-34a-5p mimic de
activated TGF-beta1/Smad3 pathway in human hepatic stellate cells (HSC), LX-2.
Moreover, the target gene for miR-34a-5p, Smad4, was predicted and verified in LX
2 cells. Taken together, these data demonstrated that overexpression of miR-34 in
HSCs ameliorated the development and progression of liver fibrosis by targeting
Smad4 and regulating TGF-beta1/Smad3 pathway. Strategies targeting miR-34a-5p may
be of benefit in the treatment of liver fibrosis.
PMID- 29957877
TI - Estradiol-mediated regulation of hepatic iNOS in obese rats: Impact of Src,
ERK1/2, AMPKalpha, and miR-221.
AB - PURPOSE: This study aimed to investigate in vivo effects of estradiol on the
regulation of hepatic inducible nitric oxide synthase (iNOS) expression in the
high fat (HF) diet-induced obesity. Also, we aimed to investigate whether
activation of the extracellular signal-regulated kinase (ERK1/2), adenosine
monophosphate-activated protein kinase (AMPK), Src kinase, and miR-221 is
involved in estradiol-mediated regulation of iNOS in the liver of obese male
Wistar rats. Male Wistar rats were fed a standard laboratory diet or a HF diet
for 10 weeks. Half of HF rats were treated with estradiol intraperitoneally (40
MUg/kg), whereas the other half were placebo-treated 24 H before euthanasia.
Results show that estradiol treatment of HF rats decreased hepatic iNOS mRNA (P <
0.05) and protein expression (P < 0.01), the protein levels of p65 subunit of
nuclear factor kappaB (P < 0.05) and ERalpha (P < 0.05), ERK1/2 phosphorylation
(P < 0.001), and ERalpha/Src kinase association (P < 0.05). By contrast, hepatic
Src protein level (P < 0.05), AMPKalpha phosphorylation (P < 0.05), and miR-221
expression (P < 0.05) were increased in HF rats after estradiol treatment. Our
results indicate that estradiol in vivo regulates hepatic iNOS expression in
obese rats via molecular mechanisms involving ERK1/2, AMPK, Src, and miR-221
signaling.
PMID- 29957878
TI - Improved phase-attenuation duality method with space-frequency joint domain
iterative regularization.
AB - PURPOSE: A common problem of in-line phase contrast imaging systems based on
laboratory source and detector is the negative effects of finite source size,
limited spatial resolution, and system noise. These negative effects swamp the
fine phase contrast fringes and impede the precise retrieval of phase maps. This
study aims to develop a novel phase retrieval method to restore phase information
that is lost due to an imperfect system. METHODS: An improved phase-attenuation
duality (PAD) method based on space-frequency joint domain iterative
regularization (JDIR) is proposed to overcome the problems of the analytical PAD
method and the spatial-domain iterative regularization (SDIR) based PAD method.
These problems include noise robustness and optical transfer function
compensation. The proposed method was compared with the two former PAD methods
through computer simulations and experiments for validation. RESULTS: Results
reveal that JDIR method outperforms the other two methods in terms of improving
the visibility of structures in the retrieved phase maps. Among all the phase
retrieval algorithms, the TV-norm-based JDIR method performed the best in
considering the contrast and noise performance. CONCLUSIONS: This paper provides
a new method to investigate quantitative phase-contrast imaging when considering
the negative effects of an imperfect system.
PMID- 29957879
TI - Evaluation of three-dimensional superimposition technique on parietal bone of the
puberty beagle dogs.
AB - OBJECTIVES: This study aimed to (a) evaluate the stability of the parietal bone
of 6-9 months old beagles and (b) examine whether parietal regional
superimposition can provide an atraumatic and effective solution for further
maxillary expansion study. MATERIALS AND METHODS: Six prepubertal 6-month-old
male beagles were included. Six miniscrew markers were inserted into the left and
right sides of the parietal bone, and two of them were placed bilaterally near
the palatal suture. The subjects were scanned with cone beam computed tomography
(CBCT) at three time points of T0 (6 months old), T1 (7.5 months old) and T2 (9
months old), respectively. All skull models were analyzed by both the miniscrew
superimposition and the parietal regional superimposition. RESULTS: The two
superimposition methods had no significant difference (p > 0.05) in displacements
of miniscrew markers between left and right first premolars (PM1). The maxillary
superimposition between T0 and T2 indicated that the length and width of the
maxillary as well as the width of the zygoma root increased significantly (p <
0.05), while the height of maxillary had no significant difference (p > 0.05)
over the 3 months. CONCLUSIONS: The parietal bone is relatively stable for
beagles from 6 months old to 9 months old and thus can be used as a reference
region for 3D skull model superimposition of the beagle dog.
PMID- 29957880
TI - Climate and plant controls on soil organic matter in coastal wetlands.
AB - Coastal wetlands are among the most productive and carbon-rich ecosystems on
Earth. Long-term carbon storage in coastal wetlands occurs primarily belowground
as soil organic matter (SOM). In addition to serving as a carbon sink, SOM
influences wetland ecosystem structure, function, and stability. To anticipate
and mitigate the effects of climate change, there is a need to advance
understanding of environmental controls on wetland SOM. Here, we investigated the
influence of four soil formation factors: climate, biota, parent materials, and
topography. Along the northern Gulf of Mexico, we collected wetland plant and
soil data across elevation and zonation gradients within 10 estuaries that span
broad temperature and precipitation gradients. Our results highlight the
importance of climate-plant controls and indicate that the influence of elevation
is scale and location dependent. Coastal wetland plants are sensitive to climate
change; small changes in temperature or precipitation can transform coastal
wetland plant communities. Across the region, SOM was greatest in mangrove
forests and in salt marshes dominated by graminoid plants. SOM was lower in salt
flats that lacked vascular plants and in salt marshes dominated by succulent
plants. We quantified strong relationships between precipitation, salinity, plant
productivity, and SOM. Low precipitation leads to high salinity, which limits
plant productivity and appears to constrain SOM accumulation. Our analyses use
data from the Gulf of Mexico, but our results can be related to coastal wetlands
across the globe and provide a foundation for predicting the ecological effects
of future reductions in precipitation and freshwater availability. Coastal
wetlands provide many ecosystem services that are SOM dependent and highly
vulnerable to climate change. Collectively, our results indicate that future
changes in SOM and plant productivity, regulated by cascading effects of
precipitation on freshwater availability and salinity, could impact wetland
stability and affect the supply of some wetland ecosystem services.
PMID- 29957882
TI - Transplantation within the era of anti-IL-1 therapy: case series of five patients
with familial Mediterranean fever-related amyloidosis.
PMID- 29957881
TI - A large epidemiological study of erythema multiforme in France, with emphasis on
treatment choices.
PMID- 29957883
TI - Independent and interactive effects of immune activation and larval diet on adult
immune function, growth and development in the greater wax moth (Galleria
mellonella).
AB - Organisms in the wild are likely to face multiple immune challenges as well as
additional ecological stressors, yet their interactive effects on immune function
are poorly understood. Insects are found to respond to cues of increased
infection risk by enhancing their immune capacity. However, such adaptive
plasticity in immune function may be limited by physiological and environmental
constraints. Here, we investigated the effects of two environmental stressors -
poor larval diet and an artificial parasite-like immune challenge at the pupal
stage - on adult immune function, growth and development in the greater wax moth
(Galleria mellonella). Males whose immune system was activated with an artificial
parasite-like immune challenge had weaker immune response - measured as strength
of encapsulation response - as adults compared to the control groups, but only
when reared on high-nutrition larval diet. Immune activation did not negatively
affect adult immune response in males reared on low-nutrition larval diet,
indicating that poor larval diet improved the capacity of the insects to respond
to repeated immune challenges. Low-nutrition larval diet also had a positive
independent effect on immune capacity in females, yet it negatively affected
development time and adult body mass in both sexes. As in the nature immune
challenges are rarely isolated, and adverse nutritional environment may indicate
an elevated risk of infection, resilience to repeated immune challenges as a
response to poor nutritional conditions could provide a significant fitness
advantage. This study highlights the importance of considering environmental
context when investigating the effects of immune activation in insects.
PMID- 29957884
TI - Local environment, not local adaptation, drives leaf-out phenology in common
gardens along an elevational gradient in Acadia National Park, Maine.
AB - PREMISE OF THE STUDY: Climate-driven changes in phenology are substantially
affecting ecological relationships and ecosystem processes. The role of variation
among species has received particular attention; for example, variation among
species' phenological responses to climate can disrupt trophic interactions and
can influence plant performance. Variation within species in phenological
responses to climate, however, has received much less attention, despite its
potential role in ecological interactions and local adaptation to climate change.
METHODS: We constructed three common gardens across an elevation gradient on
Cadillac Mountain in Acadia National Park, Maine, to test population-level
responses in leaf-out phenology in a reciprocal transplant experiment. The
experiment included three native species: low bush blueberry (Vaccinium
angustifolium), sheep's laurel (Kalmia angustifolia), and three-toothed
cinquefoil (Sibbaldiopsis tridentata). KEY RESULTS: Evidence for local adaptation
of phenological response to temperature varied among the species, but was weak
for all three. Rather, variation in phenological response to temperature appeared
to be driven by local microclimate at each garden site and year-to-year variation
in temperature. CONCLUSIONS: Population-level adaptations in leaf-out phenology
appear to be relatively unimportant for these species in Acadia National Park,
perhaps a reflection of strong genetic mixing across elevations, or weak
differences in selection on phenological response to spring temperatures at
different elevations. These results concur with other observational data in
Acadia and highlight the utility of experimental approaches to understand the
importance of annual and local site variation in affecting phenology both among
and within plant species.
PMID- 29957886
TI - Effects of liraglutide, metformin and gliclazide on body composition in patients
with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized
trial.
AB - AIMS/INTRODUCTION: To compare the effects of gliclazide, liraglutide and
metformin on body composition in patients with type 2 diabetes mellitus with non
alcoholic fatty liver disease. MATERIALS AND METHODS: A total of 85 patients were
randomly allocated to receive gliclazide (n = 27), liraglutide (n = 29) or
metformin (n = 29) monotherapy for 24 weeks. Body composition was measured using
dual-energy X-ray absorptiometry. RESULTS: Liraglutide and metformin reduced
total, trunk, limb, android and gynoid fat mass; this also led to weight
reduction. However, gliclazide treatment produced no significant changes in
weight or fat mass, likely because reductions in fat mass were concomitant with
increases in lean tissue mass. Blood glucose concentrations and glycated
hemoglobin levels improved in all treatment arms; levels of the latter were lower
in patients treated with liraglutide and metformin. Serum alanine
aminotransferase concentrations decreased in all treatment arms, whereas serum
aspartate aminotransferase concentrations were reduced only by liraglutide and
metformin. In all patients, weight loss and total, trunk, limb, and android fat
mass reductions were positively correlated with decreases in serum alanine
aminotransferase and aspartate aminotransferase levels, whereas reductions in
waist circumference were positively correlated with lower serum alanine
aminotransferase levels. CONCLUSIONS: Compared with gliclazide, liraglutide and
metformin monotherapies result in greater weight loss, reductions in body fat
mass, and better blood glucose control among type 2 diabetes mellitus patients
with non-alcoholic fatty liver disease. Reductions in weight, fat mass and waist
circumference favorably affect hepatic function.
PMID- 29957885
TI - Can doctors identify older patients at risk of medication harm following hospital
discharge? A multicentre prospective study in the UK.
AB - AIMS: Medication-related harm (MRH) is common in older adults following hospital
discharge. In resource-limited health systems, interventions to reduce this risk
can be targeted at high-risk patients. This study aims to determine whether (1)
doctors can predict which older patients will experience MRH requiring healthcare
following hospital discharge, (2) clinical experience and confidence in
prediction influence the accuracy of the prediction. METHODS: This was a
multicentre observational prospective study involving five teaching hospitals in
England between September 2013 and November 2015. Doctors discharging patients
(aged >=65 years) from medical wards predicted the likelihood of their patient
experiencing MRH requiring healthcare (hospital readmission or community
healthcare) in the initial 8-week period post-discharge. Patients were followed
up by senior pharmacists to determine MRH occurrence. RESULTS: Data of 1066
patients (83%) with completed predictions and follow-up, out of 1280 recruited
patients, were analysed. Patients had a median age of 82 years (65-103 years),
and 58% were female. Most predictions (85%) were made by junior doctors with less
than 5 years' clinical experience. There was no relationship between doctors'
predictions and patient MRH (OR 1.10, 95% CI 0.82-1.46, P = 0.53), irrespective
of years of clinical experience. Doctors' predictions were more likely to be
accurate when they reported higher confidence in their prediction, especially in
predicting MRH-associated hospital readmissions (OR 1.58, 95% CI 1.42-1.76, P <
0.001). CONCLUSIONS: Clinical judgement of doctors is not a reliable tool to
predict MRH in older adults post-discharge.
PMID- 29957887
TI - Comparative evaluation of maximum parsimony and Bayesian phylogenetic
reconstruction using empirical morphological data.
AB - The use of discrete morphological data in Bayesian phylogenetics has increased
significantly over the last years with the proposal of total evidence analysis
and the treatment of fossils as terminal taxa in Bayesian molecular dating. Both
approaches rely on the assumption that probabilistic Markov models reasonably
accommodate all the complexity of morphological evolution of discrete traits. The
performance of such morphological models used in Bayesian phylogenetics has been
thoroughly investigated, but conclusions so far were based mostly on simulated
data. In this study, we have surveyed MorphoBank and obtained a large number of
morphological matrices to evaluate Bayesian phylogenetic inference (BI) under
Lewis' Mk model in comparison with the maximum parsimony (MP) algorithm. We found
that trees estimated by both methods frequently differed and that BI generated a
larger amount of polytomic tree topologies. The number of trees contained in the
95% Bayesian credibility interval was significantly greater than the number of
equally parsimonious trees. We also investigated which factors mostly influenced
the topological difference between maximum parsimony and Bayesian tree topologies
and found that the number of terminals in morphological matrices was the variable
with the highest association with the topological distance between trees inferred
by BI and MP. Surprisingly, we show that differences between both approaches were
not influenced by increasing sample size. Our results, which were based on a
large set of empirical matrices, corroborate recent findings that BI is less
precise than MP.
PMID- 29957888
TI - The Effects of Nursing Satisfaction and Turnover Cognitions on Patient Attitudes
and Outcomes: A Three-Level Multisource Study.
AB - OBJECTIVE: To explore antecedents and outcomes of nurse self-reported job
satisfaction and dissatisfaction-based turnover cognitions, theorizing (using
Self-Determination Theory) that leaders can foster work conditions that help
fulfill innate needs, thereby fostering satisfaction of nurses and patients, and
reducing adverse events. DATA SOURCES/STUDY SETTING: Primary and secondary data
were collected within a 4-month period in 2015, from 2,596 nurses in 110 Army
treatment facilities (hospitals and clinics) across 35 health care systems. DATA
COLLECTION/EXTRACTION: We collected individual nurse responses to the Practice
Environment Scale-Nursing Work Index, in addition to aggregated archival data
from the same timeframe, including both facility-level patient satisfaction
records (the Army Provider Level Satisfaction Survey) and health care system
level adverse events records (provided by the Army Programming, Analysis, and
Evaluation office). PRINCIPAL FINDINGS: Five predictors of nurse satisfaction and
turnover cognitions emerged-supportive leadership, staffing levels, nurse
physician teamwork, adoption of nursing care practice, and advancement
opportunities. Aggregated nurse satisfaction was the most consistent predictor of
both patient satisfaction and adverse events. CONCLUSION: These findings provide
evidence of the importance of nurse attitudes in improving perceived and actual
performance across facilities and health care systems; in addition to practical
steps, managers can take to improve satisfaction and retention.
PMID- 29957890
TI - Hydrological response of biological soil crusts to global warming: A ten-year
simulative study.
AB - Biological soil crusts across the desert regions play a key role in regional
ecological security and ecological health. They are vital biotic components of
desert ecosystems that maintain soil stability, fix carbon and nitrogen,
influence the establishment of vascular plants, and serve as habitats for a large
number of arthropods and microorganisms, as well as influencing soil hydrological
processes. Changes in temperature and precipitation are expected to influence the
functioning of desert ecosystems by altering biotic components such as the
species composition of biological soil crusts. However, it remains unclear how
these important components will respond to the prolonged warming and reduced
precipitation that is predicted to occur with climate change. To evaluate how the
hydrological properties of these biological soil crusts respond to these
alterations, we used open-top chambers over a 10-year period to simulate warming
and reduced precipitation. Infiltration, dew entrapment, and evaporation were
measured as surrogates of the hydrological functioning of biological soil crusts.
It was found that the ongoing warming coupled with reduced precipitation will
more strongly affect moss in crustal communities than lichens and cyanobacteria,
which will lead to a direct alteration of the hydrological performance of
biological soil crusts. Reductions in moss abundance, surface cover, and biomass
resulted in a change in structure and function of crustal communities, decreased
dew entrapment, and increased infiltration and evaporation of biological soil
crusts in desert ecosystems, which further impacted on the desert soil water
balance.
PMID- 29957889
TI - Sinonasal aspergillosis: Outcome after topical treatment in dogs with cribriform
plate lysis.
AB - BACKGROUND: Cribriform lysis has been considered a contraindication for topical
treatment of sinonasal aspergillosis (SNA) because of concerns about drug
extravasation with resultant neurologic signs or death. OBJECTIVE/HYPOTHESIS: To
describe dogs with SNA and cribriform plate lysis treated with topical antifungal
medications. Our hypothesis was that the conventional dogma that topical therapy
should be avoided in these cases is incorrect. ANIMALS: Nine client-owned dogs
with SNA and lysis of the cribriform plate, lysis of the floor of a frontal sinus
or both detected by computed tomography (CT). METHODS: A retrospective review of
medical records was performed. Dogs that met inclusion criteria (ie, SNA
confirmed by at least 1 laboratory test, braincase affected on CT, and topical
treatment applied) were included. Size of lesions, ancillary diagnostic test
results, topical therapy, and adjuvant PO treatments were recorded. Outcome was
determined by phone calls. RESULTS: Four dogs were alive at the time of the
manuscript submission with follow-up ranging from 188 to 684 days without
neurological signs observed. All dogs were discharged without major complication
1-7 days postoperatively. One dog that had presented with a history of seizures
experienced seizure activity 2 months after treatment. CONCLUSIONS AND CLINICAL
IMPORTANCE: Topical therapy did not result in complications in these dogs in
which lytic regions as large as 16 * 22 mm2 were noted. Sinonasal aspergillosis
associated lysis of the cribriform plate; lysis of the floor of a frontal sinus
or both detected on CT is not necessarily a contraindication to topical therapy.
PMID- 29957891
TI - Readmissions after hepatopancreatic surgery: Using a yard stick to measure an
inch.
PMID- 29957892
TI - Liquid-based oral brush cytology in the diagnosis of oral leukoplakia using a
modified Bethesda Cytology system.
AB - OBJECTIVES: This study aimed to develop diagnostic criteria to identify oral
squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs)
using oral liquid-based brush cytology (OLBC), and to compare its accuracy with
the gold standard of surgical biopsy and histopathological diagnosis of oral
leukoplakia. METHODS: A total number of 134 samples were collected. All patients
underwent Orcellex(r) brush biopsy with liquid-based cytology immediately prior
to diagnostic surgical biopsy. A preliminary study was first performed utilizing
samples from 4 distinct lesion groups (20 samples) to revise the 2014 Bethesda
Cytology system for use with OLBC specimens. RESULTS: Five diagnostic groups of
OLBC for the diagnosis of OSCC and OPMDs with relevant cytopathological features
were established. From the 114 samples in the test group, 101 were included. The
other 13 were excluded due to inadequate cellularity. The test showed
sensitivity, specificity, positive predictive value and negative predictive value
of 75%, 76%, 76% and 75%, respectively, and an accuracy of 75%. The use of the
oral brush sampling technique was well accepted by multiple clinicians; however,
local anaesthetic was suggested to be useful prior to performing the brush
biopsy. CONCLUSIONS: Oral liquid-based brush cytology using the Orcellex(r) brush
and ThinPrep(r) system is a simple and minimally invasive procedure for adequate
intraepithelial sampling and can be used as an adjunct for the early detection of
oral cancer. The modified Bethesda system established useful means for OLBC
assessment that can be utilized in future studies to increase the standardization
of oral cytology assessment.
PMID- 29957893
TI - Highly antibiotic-resistant Clostridium difficile isolates from Iranian patients.
AB - AIMS: Little is known about the resistance rate and susceptibility profile of
Clostridium difficile isolates in Iran. Therefore, the aim of present study is to
assess the rate of drug-resistant C. difficile. METHODS AND RESULTS: During a 6
year period, four hospitals submitted 735 stool specimens from patients suspected
for C. difficile infections to the anaerobic bacteriology laboratory. The 46 C.
difficile isolates were subjected to disc diffusion and minimum inhibitory
concentration (MIC) Test Strips. All isolates were susceptible to vancomycin
(VAN) while the highly resistant phenotypes of metronidazole (MTZ) (67.4%),
moxifloxacin (78.3%), ciprofloxacin (69.5%) and tetracycline (82.6%) were
observed. Of more concern, 67.3% of C. difficile isolates displayed multidrug
resistant phenotypes. More than half of the isolates (n = 27, 58.6%) were
coresistant to ciprofloxacin and moxifloxacin. The MIC90 of VAN was <=2 mg l-1 ,
whereas this value for MTZ, ciprofloxacin, moxifloxacin and tetracycline was
higher than the resistance breakpoints. According to the comparison of
interpretive categories for two tests, the categorical agreement was less than
90% for VAN, ciprofloxacin and tetracycline. CONCLUSIONS: The disc diffusion
method can be used to detect the isolates with reduced susceptibility to MTZ or
moxifloxacin. The high rate of resistance to fluoroquinolones highlights the
possibility of the emergence of hypervirulent strains in our settings.
SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides data regarding the high
level of resistance against multiple antibiotics except VAN.
PMID- 29957894
TI - From breathing difficulty to dyspnea: The translation process from the patient's
story to the doctor's report in interactive medical case reports.
AB - The aim of this paper is to study the 'translation process' (Fleischman 2001)
from the patient's story into the doctor's report in interactive case reports
from professional medical journals. Interactive case reports are a relatively new
development in the genre, which has been postulated by, and adopted in, several
publication outlets. The novelty of the variety is the possibility for readers to
comment on a published case as well as the optional Patient's perspective
section, in which the patient can share their experience of illness and
treatment. In the present paper, a collection of interactive case reports derived
from professional medical journals will be examined. The material under study can
be seen as a contact situation between the lay discourse of a patient's narration
and the professional discourse of medical description. The comparison and
qualitative analysis of the two discourses referring to the same disease event
will point to different communicative accents, different means and different
effects. Drawing on the tradition of Rhetorical Genre Studies, the paper will
also emphasise the many social practices in which the variety is, and can be,
used.
PMID- 29957895
TI - How is family interaction analysed as a risk factor for schizophrenia? A cross
method comparison.
AB - In this paper, we compare two methodological approaches - Conversation Analysis
(CA) and the Communication Deviance (CD) Scale - in detecting confusing family
interaction, which is considered one of the risk factors for schizophrenia. CA is
a method for identifying and describing actions in interaction, whereas the CD
Scale presents the criteria for identifying communication defects in the field of
schizophrenia research. Our aim is to determine whether the approaches resonate
with and could complement each other in analysing the same interactional data -
i.e., a total of 10.5 hours of audio-recorded Finnish family interaction in a
psychological test in which the participants negotiate on mutual Rorschach
inkblot interpretations. The data include 585 proposals by the family members.
Here we focus on three types of proposal sequences (140 in all) where a proposal
is not followed by an acceptance or a rejection. We have earlier shown that from
the CA perspective, the family members orient to the discontinuity of these
sequences by pursuing an explicit response to a proposal, but very rarely make
the 'problematic' nature of the interaction visible to each other or the analyst.
In the present paper, we will show that the CD Scale finds communication defects
in the sequences under analysis but that the defects do not primarily involve the
discontinuity of the sequence. Thus CA and the CD Scale look at interaction from
different perspectives and disagree on what is considered an interactional
problem.
PMID- 29957896
TI - Quantitative metaphor usage patterns in Chinese psychotherapy talk.
AB - The study of metaphor in psychotherapy is undergoing a 'contextual turn',
shifting emphasis from global mechanisms underlying metaphors and therapeutic
change to their naturally occurring properties in therapist-patient interaction.
While there have been rich qualitative and contextual descriptions of metaphors
in psychotherapy, complementary quantitative accounts of metaphor usage patterns
over larger amounts of talk have been less forthcoming. This paper reports
metaphor usage patterns as associations between key contextual variables which
characterize metaphors in a dataset of Chinese psychotherapy talk. A total of
2893 metaphor vehicle terms from 29.5 hours of talk were coded for SPEAKER,
FUNCTION, TARGET, PHASE OF THERAPY, and DYAD. A loglinear analysis revealed
significant higher order associations (DYAD*TARGET*FUNCTION*PHASE;
DYAD*FUNCTION*PHASE*SPEAKER; TARGET*FUNCTION*SPEAKER), discussed as usage
patterns which bear implications for the psychotherapeutic application of
metaphor. Limitations and future research directions are discussed.
PMID- 29957897
TI - Language complexity differs between doctors and patients during contraceptive
counseling: A mixed-method study.
AB - The purpose of this study was to assess differences in language complexity for
physician and patient speech and describe differences in speech content and
literacy for medical office visits related to contraception. In a cross
sectional, mixed-methods study, we invited clinic faculty, residents, and
consecutive patients to participate in simulated clinical encounters. Two
investigators independently transcribed the recordings of these encounters. We
calculated Flesch-Kincaid Reading Level (FKRL) and Flesch Reading Ease (FRE)
scores as proxy measures for language complexity related to physician and patient
speech. We also performed content analysis of the office visit transcriptions.
Thirty-one of 33 physicians and 51 of 61 patients participated in the study,
yielding response rates of 94% and 84%, respectively. Student Independent t-tests
revealed differences in language complexity for providers and patients. On
average, physicians spoke at an Eighth-Grade (13 to 14 years old) reading level,
while patients spoke at a Fourth-Grade (nine to ten years old) level. Physicians
gave primary importance to physiologic mechanisms. Patients focused on efficacy
and side effects. We interpret the findings from the theoretical perspective of
language and culture as inseparable components of communication. Both language
and culture communicate, but at different levels of analysis. We explore both
dimensions of communication with the same data set. Although this paper is
theoretically exploratory, we believe it broadens inquiry of language use in
medicine for subsequent investigation.
PMID- 29957898
TI - The understanding of medical abbreviations across different medical departments
in a South African hospital setting.
AB - Doctors use medical abbreviations to communicate with colleagues from other
medical departments. Medical abbreviations save time, but they can be
misinterpreted and lead to treatment errors. This study evaluated the
understanding of common medical abbreviations in the Departments of Oncology,
Surgery, Gynaecology, Paediatrics and Internal Medicine at an academic hospital
in Bloemfontein, South Africa in 2012. In this cross-sectional study,
questionnaires consisting of 35 medical abbreviations were distributed to
specialists, registrars, medical officers and interns. Doctors' experiences of
communication problems due to abbreviations were documented. The total mean score
was 61.2%. Oncology abbreviations were least understood (29.1%), while Internal
Medicine abbreviations were well known (74.4%). There were significant
differences between doctors from different departments, with Oncology scoring the
highest (71.6%) and Internal Medicine and Paediatric scoring the lowest (56.0%
and 55.4%, respectively). Interns (63.2%) performed significantly better than
specialists (57.2%). Non-standard abbreviations were poorly understood (40.2%)
compared to standard abbreviations (70.8%). The findings suggest that the
understanding of medical abbreviations across medical departments is below
standard. Use of abbreviations in this multilingual environment may contribute to
poor patient care. Medical terms should be written in full, the use of non
standard medical abbreviations discouraged, and abbreviations only used when they
are widely understood and accepted as standard.
PMID- 29957899
TI - Concepts of health, ethics, and communication in shared decision making.
AB - Shared decision making depends on respectful dialogue that allows patients and
clinicians to discuss medical facts and the beliefs and values that give them
meaning for a particular patient. This dialogue is most likely to succeed when
tests and treatments are placed within a purpose-oriented landscape that sets
goals of care in the foreground so that the direction of decision making is clear
before too much focus is placed on interventional options. The beliefs and values
that guide patients allow them to identify and prioritize their most important
goals of care in light of other dimensions of decision making. These beliefs and
values will also reveal concepts of health that anchor goals of care. When
patients and clinicians disagree about treatments or goals, it may be because a
clinician is guided by a biostatistical concept of health, while a patient is
guided by one that prioritizes well-being. Such disagreements may also be
described in terms of patient preference (autonomy) and the clinician's
assessment of the patient's best interests (beneficence). By probing the beliefs
and values that explain goals of care and concepts of health, dialogue can help
reconcile disagreements in shared decision making. And even when resolution is
not forthcoming, and a decision must be 'un-shared', dialogue can demonstrate
respect for patients through the consideration clinicians show when they take
time to understand and explain.
PMID- 29957900
TI - Cardiologists' experiences and perceptions of patient involvement and
communication related to shared decision-making regarding atrial fibrillation
treatment.
AB - OBJECTIVE: To feel involved in decisions about atrial fibrillation (AF)
treatment, patients need supportive communication from cardiologists. Shedding
light on cardiologists' perceptions of patient involvement in AF care settings is
thus of importance. We examine (1) how cardiologists describe patient involvement
and communication related to shared decisionmaking regarding AF treatment, and
(2) their perceptions of efforts to involve patients in the treatment decisions.
METHODS: Ten cardiologists were interviewed in four Swedish hospitals. A
qualitative content analysis was performed on the interview data. RESULTS:
Cardiologists' perceptions of patient involvement in treatment decisions are
framed in terms of (1) ideology, (2) experience, and (3) responsibility.
CONCLUSION: By taking into account patients' feelings in the consultations, and
by actively encouraging patients to be involved, the cardiologists contributed to
patient involvement. PRACTICE IMPLICATIONS: One key to improving compliance with
legislation aimed at increasing patient involvement in treatment decisions could
lie in paying attention to physician-patient communication and the conditions for
patient involvement in decision-making about treatment.
PMID- 29957901
TI - Editorial.
PMID- 29957902
TI - Cardiac Output Assessment by Transthoracic Electrical Bio-impedance in Patients
of Acute Myocardial Infarction: Comparative Analysis with Echocardiography.
AB - Objectives: Transthoracic electrical bio-impedance (TEB) has been proposed as a
non-invasive and continuous method of cardiac output (CO) measurement, but it
still has not found wide usages in clinics. The present study measured CO, using
a new instrument NICOMON, and compared it with Echocardiography (ECHO)in acute
myocardial infarction (AMI) patients. Methods: In the present study 100 patients
of AMI were assessed by both ECHO and NICOMON for cardiac output and ECHO is
considered as a reference method for comparison. TEB CO was measured by passing
an alternating current and measuring the bio-impedance across the thorax. End
diastolic volume (EDV), End systolic volume (ESV) & Left ventricular outflow
tract (LVOT) diameter, measured by ECHO were used tocalculate CO. Various
statistical methods like "t"-test & correlation coefficient (r) were used where
found suitable. Results: Results: Mean TEB-CO (4.03+/-1.11 l/min) was
significantly higher (p<0.001) than mean ECHO-CO (3.80+/-1.28 l/min) with a mean
difference of 0.25+/-1.02 l/min. Conclusions: NICOMON measures CO non-invasively
but, it needs more elaborative studies on a larger sample to establish it as an
alternative method of ECHO for cardiac output measurement on regular basis.
PMID- 29957903
TI - Exposure to Repeated Mini-objective Structured Practical Examinations as A
Formative Assessment Tool to the Students and Faculty in Physiology Practicals.
AB - The study aimed to look at the influence of mini-Objective Structured Practical
Examinations (OSPEs) asa formative assessment tool for students and teachers. All
first year MBBS students of 2013-14 batch ofSt. John's Medical College (n=60)
went through four mini-OSPE sessions consisting of 5 sets of 6 stationseach
during 3 months of hematology practicals and final OSPE after 2 months. Feedback
of the studentsand faculty was obtained. The students were categorized into
tertiles based on the cumulative scoresobtained in the first three-OSPEs and
final-OSPE session and were significantly associated from Chi squaretest. [c2(4,
N=54) =15.2, p=0.004]. Low performers with high probability of performing poorly
were recognizedearly in the term. High performers largely remained so and mid
performers showed highly variable performance.The feedback obtained supported the
role of OSPE as a formative assessment tool. Thus, OSPE could be used as a
formative tool for students and teachers.
PMID- 29957904
TI - A Novel Practical to Demonstrate Systemic and Local Regulation of Circulation in
a Human Subject.
AB - Purpose of the study: Systemic and local regulation of peripheral circulation is
a vital concept to be taughtto undergraduate medical students. There is lack of
an effective practical module to demonstrate and reinforce the theoretical
understanding of this concept. Methodology: We designed a simple feasible novel
practical using finger pulse recording coupled with hand grip test and reactive
hyperemia protocol to elicit systemic and local regulation of peripheral
circulation respectively. Main findings: The reduction in finger pulse amplitude
during hand grip contralateral to the exercising hand demonstrates systemic
regulation while the isolated ipsilateral increase in finger pulse amplitude
during reactive hyperemia demonstrates local regulation. Conclusion: : Here we
propose a simple novel practical for effective demonstration of systemic and
local regulation of circulation for under-graduate teaching in physiology.
PMID- 29957905
TI - Effect on platelet aggregation activity: extracts from 31 Traditional Chinese
Medicines with the property of activating blood and resolvingstasis.
AB - OBJECTIVE: To evaluate the anti-platelet aggregation effects of extracts from 31
Traditional ChineseMedicines (TCM) with the property of activating blood and
resolving stasis in terms of TCM theory. METHODS: The 31 TCMs extracts were
prepared using water, 90% ethanol and ethyl acetate., and theeffects on anti
platelet aggregation were tested on a platelet aggregation analyzer in vitro with
adenosine5'-diphosphate, bovine thrombin and arachidonic acid (AA) as aggregation
inducers, respectively.Aspirin was the positive control. RESULTS: Lots of the
tested TCMs had inhibitory effects with concentration-dependent manner onplatelet
aggregations induced by various agonists. Especially, some of the TCMs such as
Chuanxiong(Rhizoma Chuanxiong), Yanhusuo (Rhizoma Corydalis Yanhusuo) and Danshen
(Radix Salviae Miltiorrhizae)showed good anti-platelet aggregation effect similar
or higher than that in positive control group. CONCLUSION: The study provided
scientific references that several TCMs such as Chuanxiong (RhizomaChuanxiong),
Yanhusuo (Rhizoma Corydalis Yanhusuo) and Danshen (Radix Salviae
Miltiorrhizae),possess the property of anti-platelet aggregation.
PMID- 29957906
TI - Cardiac Autonomic Neuropathy in Type II Diabetes Mellitus Patients and its
Association with the Age of the Patient, Duration ofDisease and Glycemic Control.
AB - Objectives: Evaluation of association between age, duration of disease and
glycemic control in type IIdiabetics with the incidence of cardiac autonomic
neuropathy (CAN). Methods: Study includes 50 Type II diabetic patients of 40-60
years age of both the genders with different duration of disease. CAN was
evaluated in terms of presence of resting tachycardia, loss of sinus arrhythmia
and heart rate response to Valsalva maneuver by electrocardiogram (ECG). An R-R
variation with respiration of >15 beats per minute was taken normal, while 10-15
beats and <10 beats per minute were taken asborderline and definitive CAN
respectively. Valsalva ratio is 1.2 or more taken as normal; Values of 1 to 1.2 &
values less or equal to 1 were taken as borderline and definitive CAN
respectively. If any two of them found positive, then presence of CAN was
confirmed. Correlation between age, duration of disease and glycemiccontrol with
incidence of CAN was assessed. Results: The incidence of CAN in diabetics based
on above tests is 16%. There is a significant negative correlation between
duration of disease and Glycated hemoglobin with deep breathing difference. (r =
0.423**, p=0.002) (r = -0.207*, p = 0.04). Conclusion: Poorer the glycemic
control and longer the duration of the disease higher the incidence of CAN in
type II diabetics.
PMID- 29957907
TI - Effect of brain functional recovery decoction on expression of vascular
endothelial growth factor and Ang-1 protein in a rat cerebralischemia reperfusion
model.
AB - OBJECTIVE: To investigate the effect of brain functional recovery decoction
(BFRD) on expression ofvascular endothelial growth factor (VEGF) and angiopoietin
1 (Ang-1) protein in rats with cerebralischemia reperfusion injury, and to
explore the mechanism of action of BFRD. METHODS: Using the suture-occlusion
method, a Wistar rat model of focal cerebral ischemia reperfusionwas established.
The rats were randomly divided into treatment group, model group, andsham
operation group. The treatment group was administered BFRD. In situ hybridization
was usedto detect VEGF mRNA expression. Immunohistochemistry was used to observe
expression of Ang-1 protein. RESULTS: VEGF mRNA expression was greater in the
model group compared with the sham operationgroup (P < 0.05); Ang-1 protein
expression was more obvious in the treatment group than themodel group (P <
0.05). CONCLUSION: BFRD promoted VEGF mRNA and Ang-1 protein expression in the
brains of ratswith cerebral ischemia, suggesting increased angiogenesis.
PMID- 29957908
TI - The complexities of biosimilars and the regulatory approval process.
AB - Created via the Biologics Price Competition and Innovation Act, the biosimilar
class of drugs was conceived as an opportunity to introduce competition for
commonly used biologics following loss of patent protection and market
exclusivity, similar to the generic paradigm that has helped sustain access and
innovation for more than 3 decades. The FDA approves a biosimilar after a
manufacturer establishes that the product is highly similar to a previously
approved originator biologic reference product without any clinically meaningful
differences in safety, purity, and potency. Given the concerns about increasing
healthcare costs and this new opportunity to reduce the expense associated with
biologics, including many commonly used oncology medications, the use of
biosimilars will likely increase as numerous stakeholders, including managed care
organizations, begin to implement policies to encourage adoption. As biosimilars
are a relatively new class of drugs, clinical, scientific, and regulatory aspects
continue to evolve and improve. Understanding those various aspects can improve
clinician acceptance and advance the science of biologics and biosimilars. In
this report, various factors are addressed to improve the knowledge of
biosimilars, including clinical, manufacturing, and cost considerations.
PMID- 29957909
TI - Opportunities and challenges in biosimilar uptake in oncology.
AB - There are now 10 approved biosimilars in the United States, including 3 oncology
drugs, and at least 16 others in late-stage development. The introduction of
competition into the biologic space launches a new era in the treatment of
cancer, possibly increasing access to the extremely costly biologics. The most
important and influential stakeholders for biosimilar acceptance and usage are
healthcare providers, such as pharmacists and physicians, as well as patients.
Gaining their support requires extensive education, postmarketing
pharmacovigilance, resolving concerns about immunogenicity, and allowing
interchangeability and substitution. Patients require education on the basic
definition of biosimilars versus generic drugs, how biosimilars are tested and
approved, costs, and availability of clinical trials. Meanwhile, payers may need
to find ways to incentivize physicians to prescribe biosimilars over biologics,
as well as to provide information on cost and quality directly to patients in
order to drive uptake. Finally, legal challenges to approved and pending
biosimilars have limited the market access of these agents.
PMID- 29957910
TI - Do Congenitally Blind Individuals have Better Haptic Object Perception Compared
to Blindfolded Sighted Individuals?
AB - Objective: Haptic perceptual enhancement in congenitally blind people is a
subject of intense debate. Thereis no consensus whether the congenitally blind
get the benefit of their haptic experience or the sighted getthe benefit of
previous visual experience when it comes to recognizing objects by manual
exploration usingdifferent constraints. The present study compared haptic object
perception between congenitally blind andblindfolded sighted participants in a
situation where manual exploration of objects was constrained. Methods:Thirty
congenitally blind braille readers and 30 age and gender matched controls were
studied. All participantswere required to identify the objects haptically,
without the aid of vision. Manual exploration of the objectswas constrained by
permitting touching of the object with only the exposed tip of the index finger
with theaim to limit cues about material information. Performance was evaluated
in terms of speed and accuracywith which objects were identified. Result: The
recognition time analysis showed that congenitally blindparticipants recognize
objects much faster than blindfolded sighted participants. The analysis of
hapticrecognition rates showed that congenitally blind participants identified
the objects more accurately comparedto blindfolded normal sighted individuals.
Conclusion: Congenitally blind individuals appear to possess adefinite enhanced
haptic perceptual ability allowing for faster and more accurate recognition of
objects even when manual exploration is constrained.
PMID- 29957912
TI - Hindi and English Letter Cancellation Tasks : Does language have an effect on
performance?
AB - Letter Cancellation Tasks (LCTs) are paper-pencil based psychomotor tasks that
are commonly used toassess cognitive functions of healthy volunteers and
patients. The performance on LCTs can be affected by the proficiency in the
language used for the tasks. This is of importance in a country like India where
most of the population is not fluent in English. Since most of the cognitive
tests are in English, the population that can be recruited for cognitive studies
gets limited. It is therefore essential to develop tests in Indian languages like
Hindi and compare the results obtained with tests in English. The present study
evaluated the effect of Hindi and English language on performance of one, two and
three letter cancellation tasks. The study was conducted on 50 healthy volunteers
after taking written, informed consent. Subjects were asked to cancel out letters
in One, Two and Three LCTs in Hindi and English language.The total time taken to
complete each test and number of errors were statistically analyzed by unpaired t
test.The results revealed that a significantly longer time was taken to complete
Hindi LCTs than English LCTs.The error rates in the Hindi LCTs were more than
that in English with the difference in One Letter CancellationTask being
significant. This is probably because of the complex script for Hindi requiring
more time and neural resources for processing.
PMID- 29957913
TI - Shenfuqiangxin Capsule inhibits apoptosis through mitogen-activated protein
kinase signal pathway in rats with cardio-renal syndromeinduced by infrarenal
aortic-clamping.
AB - OBJECTIVE: To investigate the effect of Shenfuqiangxin capsule and the underlying
mechanism oncardio-renal syndrome (CRS) in rats induced by infrarenal aortic
clamping after renal ischaemia. METHODS: Male Wistar rats underwent infrarenal
aortic-clamping after renal ischaemia or sham operation.The surviving CRS rats
were divided randomly into three groups: CRS group (CRS + 10 mL.kg(-1). d(-1)
pure water by gavage), SFQX group (CRS + 13.2 g crude drug.kg- 1.d- 1
Shenfuqiangxin by gavage),and handleregionpeptide(HRP)group(CRS+10mg/kg HRP by
vein). Sham operation rats were given10 mL.kg-1.d-1 pure water. Treatments were
given 8 weeks after surgery, which lasted for 4 weeks. The rats were detected for
heart structure and function by transthoracic echocardiography. PPR mRNA
wasdetected by Reverse Transcription Polymerase Chain Reaction (RT-PCR). To
determine whether themitogen-activated protein kinase (MAPK) signal pathway is
included in the heart and kidney protectivefunction of Shenfuqiangxin capsule,
MAPK related proteins such as posophorylated C-Jun aminoterminal kinase (p-JNK),
posophorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2),
posophorylatedp38 (p-p38) were examined by Western Blot. Apoptosis in heart and
kidney tissues were detectedby dUTP Nick End Labeling staining. RESULTS:
Shenfuqiangxin capsule alleviated myocardial apoptosis and inhibited PRR mRNA
expressionand p-JNK, p-ERK1/2, p-p38 proteins expression in CRS rats. CONCLUSION:
All the results suggest that Shenfuqiangxin capsule improves the injured heart
and kidneyfunction maybe through inhibition of MAPK response pathway.
PMID- 29957914
TI - Correlation of Audio-Visual Reaction Time with Body Mass Index & Skin Fold
Thickness Between Runners and Healthy Controls.
AB - Audio-visual reaction time is essential for activities like driving and very
important in sports persons.Reaction time of 31 National level runners was
compared with 31 controls. Runners were subdivided into twogroups, group A (>2
yrs & < 3 yrs of training) and group B (>3 yrs & < 10 yrs of training).
Correlationbetween Body Mass Index & Skin Fold Thickness with reaction time was
also analyzed. Reaction time wassignificantly less in runners (p<0.05) when
compared to controls and also in group B. Correlation analysishas shown negative
correlation of BMI with reaction time with statistically significant value for
green colorin runners. Skin Fold Thickness also showed a negative correlation
with reaction time but was not statisticallysignificant. Improvement in reaction
time by regular practice will ultimately improve sports person's performance.
PMID- 29957915
TI - Efficacy of Ciji Hua'ai Baosheng formula on the expressions of vascular
endothelial growth factor, kinase insert domain-containing receptorand basic
fibroblast growth factor in mouse models of H(22) hepatocellular carcinoma.
AB - OBJECTIVE: To investigate the efficacy of Ciji Hua'ai Baosheng formula (CHBF) on
microvessel density(MVD) and vascular endothelial growth factor (VEGF), kinase
insert domain-containing receptor(KDR) and basic fibroblast growth factor (bFGF)
expression in serum and tumor tissue of mice receivingchemotherapy for the
treatment of H(22) hepatocellular carcinoma. METHODS: Sixty Kunming mice were
injected subcutaneously with H(22) hepatoma carcinoma cell suspensionsinto the
right anterior armpit. Seven days later, all transplanted tumor were formed and
themice were intraperitoneally injected 200 mg/kg Cytoxan (CTX) to establish the
models of tumor-bearingmouse chemotherapy, then they were randomly divided into
model group, continuing CTX chemotherapygroup (CTX group), and three CHBF (117,
58.5 and 29.25 g/kg) groups. After ten days oftreatments, histology was observed,
contents of VEGF, KDR and bFGF in serum and tumor tissuewere measured by enzyme
linked immunosorbent assay (ELISA), VEGF and bFGF protein expressionand MVD
tagged by CD34 were detected by immunohistochemistry. RESULTS: MVD in CHBF (117,
58.5 g/kg) and CTX groups was significantly lower than that in modelgroup (P <
0.01); expressions of VEGF, KDR and bFGF in serum and tumor tissue in CHBF (117
g/kg)group were less than those in model group (P < 0.05; P < 0.01); the
expressions of MVD, VEGF andbFGF in tumor tissue of CHBF (117 g/kg) group were
also less than those in CTX group (P < 0.05;P < 0.01). CONCLUSION: CHBF can
effectively reduce the expression of VEGF, KDR and bFGF in serum and tumortissue,
and decrease MVD and delay tumor progression.
PMID- 29957916
TI - Effects of electroacupuncture at Guanyuan (CV 4) or Sanyinjiao (SP 6) on
hypothalamus-pituitary-ovary axis and spatial learning andmemory in female SAMP8
mice.
AB - OBJECTIVE: To investigate the effects of electroacupuncture (EA) at the Guanyuan
(CV 4) orSanyinjiao (SP 6) acupoints on the hypothalamus-pituitary-ovary (HPO)
axis and spatial learningand memory in female mice. METHODS: Nine-month-old
female mice with senescence-accelerated mouse prone 8 (SAMP8)were divided into
three groups: the disease model, EA-Guanyuan and EA-Sanyinjiao groups.
Concurrently,9-month old female mice with senescence-accelerated mouse resistance
1 (SAMR1)were set as the control model group. The two treatment groups were given
the same pattern of EAstimulation. Gonadotropin-releasing hormone, luteinizing
hormone, follicle-stimulating hormone(FSH) and Serum estradiol levels in the
Hypothalamus-pituitary-ovary axis were assessed by enzyme-linked immunosorbent
assay to determine the HPO axis function level. Spatial learning andmemory were
assessed by the Morris Water Maze(MWM) test. RESULTS: (a) HPO axis: compared with
the control model group, the disease model group displayed adecrease in E2 levels
(P < 0.01), and an increase in GnRH, LH and FSH levels (P < 0.01). E2 levels
wereincreased in EA treatment groups compared with the disease model group (P <
0.05). In contrast,GnRH and LH and FSH levels were reduced (P < 0.05). EA
Sanyinjiao group was superior thanEA-Guanyuan group on increasing E2 and
declining GnRH levels (P < 0.01). (b) The MWM test demonstratedthat the response
latency in the EA-Sanyinjiao treatment group declined from day 2 to day5 compared
with the disease model group (P < 0.05), whereas the EA-Guanyuan treatment
groupshowed no significant difference. CONCLUSION: EA can regulate hormone (E2,
FSH, LH, GnRH) levels in the HPO axis and the spatiallearning and memory ability
in female SAMP8 mice. Moreover, this effect may have been morepronounced in the
EA-Sanyinjiao group than the EA-Guanyuan group. The underlying mechanism ofthe EA
induced changes may be related to gonadal hormone shifts in the HPO axis,
followed by an improvementin spatial learning and memory.
PMID- 29957917
TI - Comparison of Cardiovascular Parameters and Cardiac Autonomic Activity of Obese
and Normal Weight School Children in Puducherry.
AB - Background and Aim: Worldwide, incidence of childhood obesity is on the rising
trend and obese children are more vulnerable to various health disorders. This
study was done to assess and compare the cardiovascular parameters and Heart rate
variability (HRV) parameters of obese school children with children with normal
Body Mass Index (BMI). Methods: Thirty obese children (BMI ? 95th percentile)
aged 9-12 years and 30 age and sex matched children with normal BMI (BMI 5th to
below 85th percentile) were included in test and control groups respectively.
Mann Whitney U test was done to detect the difference between the two groups with
respect to systolic blood pressure (SBP), diastolic blood pressure (DBP) and HRV
parameters. Sub-analyses were also doneto compare the data of boys of control and
test groups and the data of girls of control and test groups. Results: SBP, DBP
and Mean arterial pressure (MAP) were significantly high in the test group.
However, there was no significant difference between test and control groups with
respect to HRV parameters. Subanalyses revealed that the obese boys had a
significantly high SBP, DBP, MAP, rate pressure product (RPP) and a significantly
low total HRV while the obese girls had a significantly raised SDNN, RMSSD,pNN50,
LF power, HF power and total HRV. Conclusion: The obese children had a
significantly raised blood pressure. There was no difference in the HRV
parameters of normal weight and obese children. However, obese boys had a
significantly reduced total HRV when compared to normal weight boys while the
obese girls had a significantly raised total HRV when compared to normal weight
girls. The various physiological changes during puberty and the time of onsetof
puberty may have a varying impact on the cardiac autonomic status of obese male
and female children.
PMID- 29957918
TI - Serum from asthmatic rat treated with acupuncture inhibits acetylcholine-induced
contractile responses of airway smooth muscle cells.
AB - OBJECTIVE: To investigate the influence of serum from asthmatic rat treated with
acupuncture (acupunctureserum) on the contractile responses of airway smooth
muscle cells (ASMCs). METHODS: OVA-induced asthmatic rats were subject to
acupuncture treatment at the points of Dazhui(GV 14), Fengmen (BL 12), and Feishu
(BL 13). The resulting serum was collected, as well as serumfrom normal animals.
Contraction of ASMCs was induced with 10 MUM acetylcholine (Ach), and
acupunctureserum or normal serum was supplemented 15 min later. The effects of
the sera on thechanges in cell length, width, and surface area were monitored in
real time via a live cell imaging system. RESULTS: The contraction rates of ASMCs
15 min and 30 min after Ach stimulation reached 38.2% +/-3.8% and 49.7% +/- 4.6%,
both of which were significantly higher than unstimulated control cells (P
<0.01). Acupuncture serum at the 1:100 dosage reduced the contraction rate of
ASMCs from 40.1% +/-5.1% to 17.6% +/- 6.5% (P < 0.01). Thus, the treatment
significantly inhibited the Ach-induced contractileresponses of ASMCs and yielded
a relaxation efficiency of 58%, which was greater than theeffects obtained with a
1:250 dosage. Treatment with acupuncture serum at 1:500 dosage or normalserum
displayed no clear effect of suppressing Ach-induced contraction of ASMCs.
CONCLUSION: Our data suggest that acupuncture serum has the effect of inhibiting
Ach-induced contractionof ASMCs, thereby promoting relaxation of the cells.
PMID- 29957919
TI - Microvascular pathological features and changes in related injury factors in a
rat acute blood stasis model.
AB - OBJECTIVE: To examine the microvascular pathological characteristics and changes
in related injuryfactors in a rat model of acute blood stasis. METHODS: A total
of 75 Sprague-Dawley rats were divided randomly and equally into a control
groupand four experimental groups assessed at different times after the induction
of stasis (0, 1, 3 or 6 h afterstasis) (n = 15). The acute blood stasis model was
established through rat tail-vein injection ofhigh-molecular-weight dextran.
After Electrocardiograph (ECG) detection at predetermined times (0,1, 3 and 6 h
after induction of stasis), the rats were sacrificed and blood and cardiac
samples were harvestedfor analysis. Hematoxylin-eosin (HE) staining and
transmission electron microscopy were usedfor histopathological detection; an
enzyme linked immunosorbent assay (ELISA) was used to detectthromboxane B2 (TXB2)
and 6-keto-prostaglandin F1alpha (6-Keto-PGF1alpha) concentrations; a real
timepolymerase chain reaction (PCR) reaction system was used to detect
intercellular adhesion molecule1 (ICAM-1) and vascular cell adhesion molecule1
(VCAM-1) mRNA expression; western blotting wasused to detect vascular endothelial
cadherin (VE-cadherin) protein expression. RESULTS: The ST segment in the ECG
showed gradual elevation after induction of stasis and continuedelevation at a
high level at 3 and 6 h. The HE staining showed changes in myocardial cell
necrosisand tissue dissociation after the induction of stasis, along with
inflammatory infiltration. Results oftransmission electron microscopy showed
immediate changes in blood stasis and lumen occlusion inthe microvasculature,
along with endothelial cell swelling. After the induction of stasis, TXB2
concentrationsgradually increased while 6-Keto-PGF(1alpha) concentrations were
immediately significantly reduced.The TXB(2)/6-Keto-PGF(1alpha) ratio was
maintained at a high level. ICAM-1 mRNA expression showedan unstable elevation
while VCAM-1 mRNA expression was significantly reduced after the inductionof
stasis. Compared with the control group, VE-cadherin protein expression increased
at 0 and 3 h afterthe induction of stasis, while no change occurred at 1 and 6 h.
CONCLUSION: The pathological manifestations of acute blood stasis are
microvascular blood retention,lumen stenosis and even occlusion. The condition is
also called "blood coagulation and weep" inTraditional Chinese Medicine. The
blood stasis model resulted in the injury and necrosis of endothelialcells and
cardiomyocytes, along with the presence of an imbalance of vasomotor factor
levels, plateletactivation, and increases in the expression of adhesion molecules
and endothelial barrier dysfunction,which corresponds to "blood failed to
nourish" in Traditional Chinese Medicine.
PMID- 29957920
TI - Sub-clinical Hypothyroidism in Type 2 Diabetes Mellitus Patients in a Tertiary
Care Hospital, Mysore.
AB - Thyroid diseases and type 2 diabetes mellitus are the two most common endocrine
disorders encounteredin clinical practice. Diabetes mellitus and thyroid
disorders are shown to mutually influence each other. Thepresent study was done
to assess and compare the thyroid function tests in diabetes mellitus patients
andnormal healthy volunteers. This is a cross-sectional, age-matched,
comparative, hospital based study. Type2 Diabetes mellitus patients without
hypothyroidism attending the medicine outpatient department (OPD) oradmitted in
the medicine wards were screened and then included as cases (30 patients). The
normal healthyvolunteers without diabetes mellitus or hypothyroidism were
screened and included for control group (30Patients).In this study the mean and
standard deviation (S.D.) of thyroid stimulating hormone (TSH) was
statistically,significantly higher in the diabetes mellitus group (5.48+/-2.32
mIU/dl), when compared to control group(2.91+/-1.44 mIU/dl). This sub clinical
hypothyroidism leads to dyslipidemia. The results also showed elevatedtotal
cholesterol, low density lipoprotein (LDL) in diabetes mellitus group, when
compared to control group.Thus, subclinical hypothyroidism in type 2 diabetes
mellitus can aggravate the classical risk factors suchas hypertension and
dyslipidemia, arising from an undiagnosed thyroid dysfunction and can lead to an
increased cardiovascular risk in these patients.
PMID- 29957921
TI - Novel Targets for Parkinson's Disease: Addressing Different Therapeutic Paradigms
and Conundrums.
AB - Parkinson's disease (PD) is a neurodegenerative disease that is pathologically
characterized by degeneration of dopamine neurons in the substantia nigra pars
compacta (SNpc). PD leads to clinical motor features that include rigidity,
tremor, and bradykinesia. Despite multiple available therapies for PD, the
clinical features continue to progress, and patients suffer progressive
disability. Many advances have been made in PD therapy which directly target the
cause of the disease rather than providing symptomatic relief. A neuroprotective
or disease modifying strategy that can slow or cease clinical progression and
worsening disability remains as a major unmet medical need for PD management. The
present review discusses potential novel therapies for PD that include recent
interventions in the form of immunomodulatory techniques and stem cell therapy.
Further, an introspective approach to identify numerous other novel targets that
can alleviate PD pathogenesis and enable physicians to practice multitargeted
therapy and that may provide a ray of hope to PD patients in the future are
discussed.
PMID- 29957922
TI - Remarkable Amplification of Polyethylenimine-Mediated Gene Delivery Using
Cationic Poly(phenylene ethynylene)s as Photosensitizers.
AB - Conjugated polymers can serve as good photosensitizers in biomedical
applications. However, it remains unknown whether they are phototoxic to the
supercoiled structure of DNA in improving gene delivery by the photochemical
internalization (PCI) strategy, which complicates the application of conjugated
polymers in gene delivery. In this work, we introduced a trace amount of cationic
poly(phenylene ethynylene)s (cPPEs) into the polymeric shell of branched
polyethylenimine (BPEI)/DNA complexes, studied the photosensitization of singlet
oxygen by cPPEs, and confirmed that the supercoiled DNA is undamaged by the
singlet oxygen generated by the photoexcitation of cPPEs. By taking advantage of
the cPPE-mediated PCI effect, we report that the addition of the trace amount of
cPPEs to the outer shell of the BPEI/DNA polyplexes could greatly amplify the
transfection of gene green fluorescent protein on tumor cells with the efficiency
from 14 to 86% without decreasing the cell viabilities, well solving the problem
with a poor transfection capability of BPEI under low DNA-loading conditions. Our
strategy to employ conjugated polymers as photosensitizing agents in gene
delivery systems is simple, safe, efficient, and promising for broad applications
in gene delivery areas.
PMID- 29957923
TI - Anomalous Pressure Characteristics of Defects in Hexagonal Boron Nitride Flakes.
AB - Research on hexagonal boron nitride (hBN) has been intensified recently due to
the application of hBN as a promising system of single-photon emitters. To date,
the single photon origin remains under debate even though many experiments and
theoretical calculations have been performed. We have measured the pressure
dependent photoluminescence (PL) spectra of hBN flakes at low temperatures by
using a diamond anvil cell device. The absolute values of the pressure
coefficients of discrete PL emission lines are all below 15 meV/GPa, which is
much lower than the pressure-induced 36 meV/GPa redshift rate of the hBN bandgap.
These PL emission lines originate from atom-like localized defect levels confined
within the bandgap of the hBN flakes. Interestingly, the experimental results of
the pressure-dependent PL emission lines present three different types of
pressure responses corresponding to a redshift (negative pressure coefficient), a
blueshift (positive pressure coefficient), or even a sign change from negative to
positive. Density functional theory calculations indicate the existence of
competition between the intralayer and interlayer interaction contributions,
which leads to the different pressure-dependent behaviors of the PL peak shift.
PMID- 29957924
TI - Ultralow Sample Volume Cupric Sulfate Oxidation Method for the Analysis of
Dissolved Lignin.
AB - A novel cupric sulfate (CuSO4) oxidation method was developed to enable the
analysis of dissolved lignin phenols in small volumes of open ocean seawater
(<200 mL for deep ocean) or river water (<17 mL) samples. Dissolved lignin
phenols were isolated by automated reversed-phase (octadecyl) extraction from
seawater before oxidation, whereas for freshwater samples, oxidation was
performed without prior extraction. Optimized reaction conditions using alkaline
CuSO4 at 150 degrees C effectively limited losses of lignin phenols and
suppressed side reactions at 5-100 MUg of sample organic carbon. The method
yielded up to ~33% higher lignin phenol concentrations and 24-36% lower
acid/aldehyde ratios of lignin phenols than existing CuO oxidation methods. The
microscale design (200 MUL reaction volume) resulted in extremely low blanks
allowing accurate and precise quantification of lignin phenols. A comparison of
silica-based octadecyl-bonded sorbents (C18) with copolymer-type sorbents (PPL)
indicated that sorbent type affected concentrations and diagnostic ratios of
dissolved lignin phenols. For robust intercomparability of measured lignin phenol
concentrations and in consideration of method detection limits for
quantification, a constant sample organic carbon content of ~30 MUg C and the
addition of 150 MUg ascorbic acid-C are recommended. Small sample volumes avoid
time-consuming extraction steps in the field, and the simplified oxidation and
sample processing procedures make the new method ideal for high-throughput
analysis of dissolved lignin phenols in marine and freshwater environments.
PMID- 29957926
TI - Block Copolymer Micelles in Nanomedicine Applications.
AB - Polymeric micelles are demonstrating high potential as nanomedicines capable of
controlling the distribution and function of loaded bioactive agents in the body,
effectively overcoming biological barriers, and various formulations are engaged
in intensive preclinical and clinical testing. This Review focuses on polymeric
micelles assembled through multimolecular interactions between block copolymers
and the loaded drugs, proteins, or nucleic acids as translationable
nanomedicines. The aspects involved in the design of successful micellar carriers
are described in detail on the basis of the type of polymer/payload interaction,
as well as the interplay of micelles with the biological interface, emphasizing
on the chemistry and engineering of the block copolymers. By shaping these
features, polymeric micelles have been propitious for delivering a wide range of
therapeutics through effective sensing of targets in the body and adjustment of
their properties in response to particular stimuli, modulating the activity of
the loaded drugs at the targeted sites, even at the subcellular level. Finally,
the future perspectives and imminent challenges for polymeric micelles as
nanomedicines are discussed, anticipating to spur further innovations.
PMID- 29957925
TI - Nanochannel-Assisted Perovskite Nanowires: From Growth Mechanisms to
Photodetector Applications.
AB - Growing interest in hybrid organic-inorganic lead halide perovskites has led to
the development of various perovskite nanowires (NWs), which have potential use
in a wide range of applications, including lasers, photodetectors, and light
emitting diodes (LEDs). However, existing nanofabrication approaches lack the
ability to control the number, location, orientation, and properties of
perovskite NWs. Their growth mechanism also remains elusive. Here, we demonstrate
a micro/nanofluidic fabrication technique (MNFFT) enabling both precise control
and in situ monitoring of the growth of perovskite NWs. The initial nucleation
point and subsequent growth path of a methylammonium lead iodide
dimethylformamide (MAPbI3.DMF) NW array can be guided by a nanochannel. In situ
UV-vis absorption spectra are measured in real time, permitting the study of the
growth mechanism of the DMF-mediated crystallization of MAPbI3. As an example of
an application of the MNFFT, we demonstrate a highly sensitive MAPbI3-NW-based
photodetector on both solid and flexible substrates, showing the potential of the
MNFFT for low-cost, large-scale, highly efficient, and flexible optoelectronic
applications.
PMID- 29957927
TI - Recent Advances in Transition-Metal-Catalyzed/Mediated Transformations of
Vinylidenecyclopropanes.
AB - Vinylidenecyclopropanes (VDCPs), having an allene moiety connected to a highly
strained cyclopropyl group, have attracted a substantial amount of attention
since they are fascinating building blocks for organic synthesis. During recent
years, the reactions of VDCPs in the presence of a Lewis acid or a Bronsted acid
and those induced by heat or light have experienced significant advancements due
to the unique structural and electronic properties of VDCPs. Transition-metal
catalyzed reactions of VDCPs were not intensely investigated until the last 5
years. Recently, significant progress has been made in transition-metal-catalyzed
transformations of VDCPs, and they have emerged as a new direction for the
chemistry of strained small rings, especially when new types of functionalized
vinylidenecyclopropanes (FVDCPs) are used as substrates. To date, many
interesting transformations have been explored using these novel VDCPs under the
catalysis of transition metals, such as gold, palladium, or rhodium, and various
novel and useful heterocyclic or polycyclic compounds have been generated. These
new findings have enriched the chemistry of strained small carbocycles. This
Account will describe the transition-metal-catalyzed transformations of VDCPs
recently developed in our laboratory and by other groups. The chemistry of Au
catalyzed VDCPs has been enriched and extensively developed by our group. In this
respect, a new process for generating gold carbenes from VDCPs has been
disclosed. The reactivity of these new gold carbenoid species was fully
investigated, and many novel reaction modes based on these new gold carbenoid
species were explored, including oxidation reactions, intramolecular
cyclopropanations, C(sp3)-H bond functionalizations, and C-O bond cleavage
reactions. Rh-catalyzed reactions of VDCPs are another key field of transition
metal-catalyzed reactions of VDCPs. In particular, rhodium-catalyzed
cycloadditions, Pauson-Khand reactions, and C-H bond activations of FVDCPs have
been explored in detail by our group. A new trimethylenemethane rhodium (TMM-Rh)
complex generated from VDCPs was discovered and utilized as an electrophilic Rh
pi-allyl precursor. Moreover, some unprecedented highly regio- and
enantioselective asymmetric allylic substitutions via this novel TMM-Rh complex
were developed with different kinds of nucleophiles. This Account will also
summarize the recent advances in palladium-, copper-, and iron-catalyzed
cycloisomerization reactions of VDCPs reported by our group and others. These
reactions always afford the desired products with excellent chemo-, regio-,
diastereo-, and enantioselectivities, which will make them highly valuable for
the synthesis of key scaffolds in natural products and pharmaceutical molecules
in the future.
PMID- 29957928
TI - van der Waals Metallic Transition Metal Dichalcogenides.
AB - Transition metal dichalcogenides are layered materials which are composed of
transition metals and chalcogens of the group VIA in a 1:2 ratio. These layered
materials have been extensively investigated over synthesis and optical and
electrical properties for several decades. It can be insulators, semiconductors,
or metals revealing all types of condensed matter properties from a magnetic
lattice distorted to superconducting characteristics. Some of these also feature
the topological manner. Instead of covering the semiconducting properties of
transition metal dichalcogenides, which have been extensively revisited and
reviewed elsewhere, here we present the structures of metallic transition metal
dichalcogenides and their synthetic approaches for not only high-quality wafer
scale samples using conventional methods (e.g., chemical vapor transport,
chemical vapor deposition) but also local small areas by a modification of the
materials using Li intercalation, electron beam irradiation, light illumination,
pressures, and strains. Some representative band structures of metallic
transition metal dichalcogenides and their strong layer-dependence are reviewed
and updated, both in theoretical calculations and experiments. In addition, we
discuss the physical properties of metallic transition metal dichalcogenides such
as periodic lattice distortion, magnetoresistance, superconductivity, topological
insulator, and Weyl semimetal. Approaches to overcome current challenges related
to these materials are also proposed.
PMID- 29957929
TI - Structural Evolution and Microwave Dielectric Properties of xZn0.5Ti0.5NbO4-(1-
x)Zn0.15Nb0.3Ti0.55O2 Ceramics.
AB - Structure and microwave properties of xZn0.5Ti0.5NbO4-(1 - x)Zn0.15Nb0.3Ti0.55O2
ceramics in the range of x = 0.0-1.0 were investigated. Rietveld refinement
analysis and Raman spectra show that rutile- and orthorhombic-type solid
solutions formed at 0-0.2 and 0.65-1, a composite at 0.2-0.64. In the solid
solution regions, chemical bonds are enlarged. In this case, the Zn/Ti/Nb-O1 bond
covalency and bond susceptibility are reduced, and lattice energy and thermal
expansion coefficient increase along with x increases, which is mainly
responsible for the development of microwave dielectric properties. Furthermore,
far-infrared spectra and a classical oscillator model were used to discuss the
intrinsic dielectric properties in detail. Temperature stable ceramic was
obtained for x = 0.516: epsilonr ~ 46.11, Q * f ~ 27 031 GHz, and tauf ~ -1.51
ppm/ degrees C, which is promising for microwave applications.
PMID- 29957930
TI - Hypoxia-Triggered Nanoscale Metal-Organic Frameworks for Enhanced Anticancer
Activity.
AB - The oxygen-dependent feature of most photosensitizers (PSs) and the aggravated
hypoxia tumor microenvironment seriously impede the photodynamic therapy (PDT)
effectiveness. However, this undesirable impediment can be utilized to further
trigger the activation of hypoxia-sensitive prodrugs. Moreover, a combined
therapy can be used by associating PDT with hypoxia-activated chemotherapy.
Herein, a multifunctional Hf-porphyrin nanoscale metal-organic framework (NMOF)
platform [Hf/tetra(4-carboxyphenyl)porphine (TCPP)] has been synthesized, with a
high porphyrin loading capacity and a well-ordered coordination array preventing
porphyrin self-quenching, thus greatly improving the generation efficiency of
reactive oxygen species (ROS), which is helpful for PDT. As-synthesized Hf-TCPP
nanoparticles possess more than 50 wt % of TCPP PS content, good crystallization,
and a large Brunauer-Emmett-Teller surface for further loading the hypoxia
activated prodrug [tirapazamine (TPZ)] in a high-loading content. Additionally,
subsequent surface modification with a dopamine-derived polymer (DOPA-PIMA-mPEG)
significantly improves their dispersibility and structural stability, and the
controlled release kinetics of TPZ. Such a nanoplatform can efficiently produce
ROS for PDT upon irradiation, and also the depletion of the oxygen could further
aggravate the hypoxic environment of tumors to induce the activation of TPZ for
achieving an enhanced treatment efficacy. This work demonstrates the great
advantages of an NMOF-based platform in antitumor therapies for combined PDT and
hypoxia-activated chemotherapy.
PMID- 29957931
TI - Electrically Driven Reversible Magnetic Rotation in Nanoscale Multiferroic
Heterostructures.
AB - Electrically driven magnetic switching (EDMS) is highly demanded for next
generation advanced memories or spintronic devices. The key challenge is to
achieve repeatable and reversible EDMS at sufficiently small scale. In this work,
we reported an experimental realization of room-temperature, electrically driven,
reversible, and robust 120 degrees magnetic state rotation in nanoscale
multiferroic heterostructures consisting of a triangular Co nanomagnet array on
tetragonal BiFeO3 films, which can be directly monitored by magnetic force
microscope (MFM) imaging. The observed reversible magnetic switching in an
individual nanomagnet can be triggered by a small electric pulse within 10 V with
an ultrashort time of ~10 ns, which also demonstrates sufficient switching
cycling and months-long retention lifetime. A mechanism based on synergic effects
of interfacial strain and exchange coupling plus shape anisotropy was also
proposed, which was also verified by micromagnetic simulations. Our results
create an avenue to engineer the nanoscale EDMS for low-power-consumption, high
density, nonvolatile magnetoelectric memories and beyond.
PMID- 29957932
TI - Visible-Light-Induced Graphitic-C3N4@Nickel-Aluminum Layered Double Hydroxide
Nanocomposites with Enhanced Photocatalytic Activity for Removal of Dyes in
Water.
AB - One of the major challenges in photodegradation of organic dyes is designing a
visible light active and highly efficient photocatalyst that can degrade both
cationic and anionic dyes. To design such an ideal catalyst, this work
synthesized graphitic-C3N4@NiAl layered double hydroxide nanocomposites (g
C3N4@NiAl-LDH NCPs) with various g-C3N4 contents through a convenient and high
yield method. The photocatalytic process was optimized by evaluating the impacts
of type of dye (cationic and anionic), photocatalyst dosage, pH, and contact
time. According to the results, the photocatalytic performance of g-C3N4@NiAl-LDH
NCPs in degradation of cationic and anionic dyes is more noticeable than the
photocatalytic activities of its discrete components. The observed improvement in
the photocatalytic performance of the g-C3N4@NiAl-LDH NCPs can be attributed to
the intimacy of their contact interfaces and a synergistic effect between
pristine g-C3N4 and NiAl-LDH, which results in effective mass transfer and
separation of photogenerated charge carriers. The impact of some charge
scavengers on the process was evaluated to define the role of each active species
and propose a possible photodegradation mechanism. The g-C3N4@Ni-Al LDH NCPs
could be reused for four cycles without any significant loss in efficiency.
PMID- 29957933
TI - Enantioselective Distribution, Degradation, and Metabolite Formation of
Myclobutanil and Transcriptional Responses of Metabolic-Related Genes in Rats.
AB - Myclobutanil (MT), a chiral fungicide, can be metabolized enantioselectively in
organisms. In this work, the associated absorption, distribution, metabolism and
transcriptional responses of MT in rats were determined following a single-dose
(10 mg.kg-1 body weight) exposure to rac-, (+)- or (-)-MT. The enantiomer
fractions (EFs) were less than 0.5 with time in the liver, kidney, heart, lung,
and testis, suggesting preferential enrichment of (-)-MT in these tissues.
Furthermore, there was conversion of (+)-form to (-)-form in the liver and kidney
after 6 h exposure to enantiopure (+)-MT. Enrichment and degradation of the two
enantiomers differed between rac-MT and MT-enantiomers groups, suggesting that MT
bioaccumulation is enantiomer-specific. Interestingly, the degradation half-life
of MT in the liver with rac-MT treatment was shorter than that with both MT
enantiomer treatments. One reason may be that the gene expression levels of
cytochrome P450 1a2 ( cyp1a2) and cyp3a2 genes in livers treated with rac-MT were
the highest among the three exposure groups. In addition, a positive correlation
between the expression of cyp2e1 and cyp3a2 genes and rac-MT concentration was
found in livers exposed to rac-MT. Simultaneously, five chiral metabolites were
detected, and the enantiomers of three metabolites, RH-9090, RH-9089, and M2,
were separated. The detected enantiomers of (+)-MT metabolites were in complete
contrast with those of (-)-MT metabolites. According to the results, a metabolic
pathway of MT in male rats was proposed, which included the following five
metabolites: RH-9089, RH-9090, RH-9090 Sulfate, M1, and M2. The possible
metabolic enzymes were marked in the pathway. The findings of this study provide
more specific insights into the enantioselective metabolic mechanism of chiral
triazole fungicides.
PMID- 29957934
TI - Stereocomplex Prodrugs of Oligo(lactic acid) n-Gemcitabine in Poly(ethylene
glycol)- block-poly(d,l-lactic acid) Micelles for Improved Physical Stability and
Enhanced Antitumor Efficacy.
AB - Herein we demonstrate the formation of stereocomplex prodrugs of oligo(l-lactic
acid) n-gemcitabine (o(LLA) n-GEM) and oligo(d-lactic acid) n-gemcitabine (o(DLA)
n-GEM) for stable incorporation in poly(ethylene glycol)- block-poly(d,l-lactic
acid) (PEG- b-PLA) micelles. O(LLA) n or o(DLA) n was attached at the amino group
(4-( N)) of GEM via an amide linkage. When n = 10, a 1:1 mixture of o(LLA)10-GEM
and o(DLA)10-GEM (o(L+DLA)10-GEM) was able to form a stereocomplex with a
distinctive crystalline pattern. Degradation of o(L+DLA)10-GEM was driven by both
backbiting conversion and esterase contribution, generating primarily o(L+DLA)1
GEM and GEM. O(L+DLA)10-GEM stably loaded in PEG- b-PLA micelles in the size
range of 140-200 nm with an unexpected elongated morphology. The resulting
micelles showed improved physical stability in aqueous media and inhibited
backbiting conversion of o(L+DLA)10-GEM within micelles. Release of o(L+DLA)10
GEM from micelles was relatively slow, with a t1/2 at ca. 60 h. Furthermore,
weekly administration of o(L+DLA)10-GEM micelles i.v. displayed potent antitumor
activity in an A549 human non-small-cell lung carcinoma xenograft model. Thus,
stereocomplexation of isotactic o(LLA) n and o(DLA) n acts as a potential prodrug
strategy for improved stability and sustained drug release in PEG- b-PLA
micelles.
PMID- 29957935
TI - Gold Fusion: From Au25(SR)18 to Au38(SR)24, the Most Unexpected Transformation of
a Very Stable Nanocluster.
AB - The study of the molecular cluster Au25(SR)18 has provided a wealth of
fundamental insights into the properties of clusters protected by thiolated
ligands (SR). This is also because this cluster has been particularly stable
under a number of experimental conditions. Very unexpectedly, we found that
paramagnetic Au25(SR)180 undergoes a spontaneous bimolecular fusion to form
another benchmark gold nanocluster, Au38(SR)24. We tested this reaction with a
series of Au25 clusters. The fusion was confirmed and characterized by UV-vis
absorption spectroscopy, ESI mass spectrometry, 1H and 13C NMR spectroscopy, and
electrochemistry. NMR evidences the presence of four types of ligand and, for the
same proton type, double signals caused by the diastereotopicity arising from the
chirality of the capping shell. This effect propagates up to the third carbon
atom along the ligand chain. Electrochemistry provides a particularly convenient
way to study the evolution process and determine the fusion rate constant, which
decreases as the ligand length increases. No reaction is observed for the anionic
clusters, whereas the radical nature of Au25(SR)180 appears to play an important
role. This transformation of a stable cluster into a larger stable cluster
without addition of any co-reagent also features the bottom-up assembly of the
Au13 building block in solution. This very unexpected result could modify our
view of the relative stability of molecular gold nanoclusters.
PMID- 29957936
TI - Strategic Design and Functionalization of an Amine-Decorated Luminescent Metal
Organic Framework for Selective Gas/Vapor Sorption and Nanomolar Sensing of 2,4,6
Trinitrophenol in Water.
AB - On the basis of the strategic design of a triazine-based dicarboxylate ligand
with two primary amino groups and one secondary amino group, an amine
functionalized autofluorescent and polar three-dimensional metal organic
framework (MOF) {[Cd(ATAIA)].4H2O} n (1), where H2ATAIA = 5-((4,6-diamino-1,3,5
triazin-2-yl)amino)isophthalic acid, has been synthesized under two different
solvothermal conditions and structurally characterized. Single-crystal X-ray
analysis reveals that 1 crystallizes in the orthorhombic polar space group Fdd2,
where each ATAIA ligand acts as a linear linker to connect four Cd(II) centers,
resulting in the formation of a three-dimensional framework with a repeat of a
double helical metal chain. It has been further characterized by elemental
analysis, UV-vis and Fourier transform infrared spectroscopy, and
thermogravimetric analysis. Its bulk phase purity and stability in aqueous acid
and base solutions are confirmed by powder X-ray diffraction. Both field emission
scanning electron microscopy and high resolution transmission electron microscopy
images of 1 reflect the formation of microflowers by self-assembly of nanopetals.
With the dehydrated framework of 1, sorption studies of different gases (N2, H2,
and CO2) as well as polar and nonpolar solvents, such as water, benzene (Bz), and
cyclohexane (Cy), have been performed. The CO2 sorption isotherm depicts type I
isotherm at 298 and 273 K and type IV isotherm at 195 K. Furthermore, with an
uptake of 129.2 cm3 g-1 (25.62 wt %) at 195 K, sorption of CO2 is selective over
N2 (77 K) and H2 (77 K) because of the strong adsorbate-adsorbent interaction as
clearly evident from an isosteric heat of adsorption ( Qst) at zero coverage of
37.5 kJ mol-1, which is exceptionally higher than that of other functionalized
MOFs. Using the ideal adsorption solution theory calculation for a CO2/N2 (15:85)
mixture, selectivity values are found to be 54.08 (298 K) and 46.96 (273 K) at
100 kPa. For a major application, activated 1 has been utilized for selective and
ultrafast detection of 2,4,6-trinitrophenol (TNP) in water with a limit of 0.94
nM (0.2 ppb), which supersedes any previous reported value. Excellent
recyclability and stability of 1 for sensing experiments have been established.
Time-resolved fluorescence studies and density functional theory calculations
have been used to establish its mechanism of action. Furthermore, a prototype
experiment for the real-time sensing of TNP in the vapor phase by fluorescence
microscopy provides an easy colorimetric monitoring.
PMID- 29957937
TI - Rebuilding C60: Chlorination-Promoted Transformations of the Buckminsterfullerene
into Pentagon-Fused C60 Derivatives.
AB - In recent years, many higher fullerenes that obey the isolated pentagon rule
(IPR) were found capable of rearranging into molecules with adjacent pentagons
and even with heptagons via chlorination-promoted skeletal transformations.
However, the key fullerene, buckminsterfullerene I h-C60, long seemed
insusceptible to such rearrangements. Now we demonstrate that
buckminsterfullerene yet can be transformed by chlorination with SbCl5 at 420-440
degrees C and report X-ray structures for the thus-obtained library of non-IPR
derivatives. The most remarkable of them are non-IPR C60Cl24 and C60Cl20 with
fundamentally rearranged carbon skeletons featuring, respectively, four and five
fused pentagon pairs (FPPs). Further high-temperature trifluoromethylation of the
chlorinated mixture afforded additional non-IPR derivatives C60(CF3)10 and
C60(CF3)14, both with two FPPs, and a nonclassical C60(CF3)15F with a heptagon,
two FPPs, and a fully fused pentagon triple. We discuss the general features of
the addition patterns in the new non-IPR compounds and probable pathways of their
formation via successive Stone-Wales rearrangements.
PMID- 29957938
TI - Organic Acid Formation from the Atmospheric Oxidation of Gem Diols: Reaction
Mechanism, Energetics, and Rates.
AB - Computational chemistry is used to investigate the gas phase reaction of several
gem diols in the presence of OH radical and molecular oxygen (3O2) as would occur
in the Earth's troposphere. Four gem diols, represented generically as R-HC(OH)2,
with R being either -H, -CH3, -HC(O), and -CH3C(O) are investigated. We find that
after the abstraction of the hydrogen atom from the C-H moiety of the diol by
atmospheric OH, molecular oxygen quickly adds onto the resulting radicals leading
to the formation of a geminal diol peroxy adduct (R-C(OO)(OH)2), which is the key
intermediate in the oxidation process. Unimolecular reaction of this R-C(OO)(OH)2
radical adduct, occurs via a proton-coupled electron transfer (PCET) mechanism
and leads to the formation of an organic acid and a HO2 radical. Further, the
barrier for the unimolecular reaction step decreases along the R substitution
series: -H, -CH3, -HC(O), -CH3C(O); this trend most likely arises from increased
internal hydrogen bonding along the series. The reaction where the R group is
CH3C(O), associated with methylglyoxal diol, has the lowest barrier with its
transition state being ~4.3 kcal/mol above the potential energy well of the
corresponding CH3C(O)-C(OO)(OH)2 peroxy adduct. The rate constants for the four
diol oxidation reactions were investigated using the MESMER master equation
solver kinetics code over the temperature range between 200 and 300 K. The
calculations suggest that once formed, gem diol radicals react rapidly with O2 in
the atmosphere to produce organic acids and HO2 with an effective gas phase
bimolecular rate constant of ~1 * 10-11 cm3/molecule s at 300 K.
PMID- 29957939
TI - Chemosensate-Induced Modulation of the Salivary Proteome and Metabolome Alters
the Sensory Perception of Salt Taste and Odor-Active Thiols.
AB - Oral stimulation with chemosensates was found to trigger changes in the
composition of the salivary proteome and metabolome, which translate into a
functional modulation of odor and taste perception. Orosensory intervention with
6-gingerol induced a significant increase in the abundance of salivary sulfhydryl
oxidase 1, which was found to catalyze the oxidative decline of odor-active 2
furfurylthiol, thus resulting in a decrease in the odorant levels in exhaled
breath, as shown by PTR-MS, and a reduction of the perceived sulfury after-smell.
Therefore, sulfhydryl oxidase 1 may be considered as a component of a molecular
network triggering oral cleansing mechanisms after food ingestion. Moreover, oral
stimulation with citric acid, followed by targeted metabolomics, was found to
induce a strong increase in salivary concentrations of minerals and, in
particular, sodium ions, whereas the other metabolites were rather unaffected.
Because of the elevated basal levels of salivary sodium after citric acid
stimulation, NaCl test stimuli were perceived as significantly less salty, most
likely due to the decreased sensory contrast. This indicates the modulation of
the salivary proteome and metabolome to be a major perireceptor event in fine
tuning odor and taste sensitivity.
PMID- 29957941
TI - Mapping Intrachannel Diffusive Dynamics of Interacting Molecules onto a Two-Site
Model: Crossover in Flux Concentration Dependence.
AB - This study focuses on how interactions of solute molecules affect the
concentration dependence of their flux through narrow membrane channels. It is
assumed that the molecules cannot bypass each other because of their hard-core
repulsion. In addition, other short- and long-range solute-solute interactions
are included into consideration. These interactions make it impossible to develop
an analytical theory for the flux in the framework of a diffusion model of solute
dynamics in the channel. To overcome this difficulty, we course-grain the
diffusion model by mapping it onto a two-site one, where the rate constants
describing the solute dynamics are expressed in terms of the parameters of the
initial diffusion model. This allows us (i) to find an analytical solution for
the flux as a function of the solute concentration and (ii) to characterize the
solute-solute interactions by two dimensionless parameters. Such a
characterization proves to be very informative as it results in a clear
classification of the effects of the solute-solute interactions on the
concentration dependence of the flux. Unexpectedly, this dependence can be
nonmonotonic, exhibiting a sharp maximum in a certain parameter range. We
hypothesize that such a behavior may constitute an element of a regulatory
mechanism, wherein maximal flux reports on the optimal solute concentration in
the bulk near the channel entrance.
PMID- 29957940
TI - Effects of N2 Binding Mode on Iron-Based Functionalization of Dinitrogen to Form
an Iron(III) Hydrazido Complex.
AB - Distinguishing the reactivity differences between N2 complexes having different
binding modes is crucial for the design of effective N2-functionalizing
reactions. Here, we compare the reactions of a K-bridged, dinuclear FeNNFe
complex with a monomeric Fe(N2) complex where the bimetallic core is broken up by
the addition of chelating agents. The new anionic iron(0) dinitrogen complex has
enhanced electron density at the distal N atoms of coordinated N2, and though the
N2 is not as weakened in this monomeric compound, it is much more reactive toward
silylation by (CH3)3SiI (TMSI). Double silylation of N2 gives a three-coordinate
iron(III) hydrazido(2-) complex, which is finely balanced between coexisting S =
1/2 and S = 3/2 states that are characterized by crystallography, spectroscopy,
and computations. These results give insight into the interdependence between
binding modes, alkali dependence, reactivity, and magnetic properties within an
iron system that functionalizes N2.
PMID- 29957942
TI - Cr L-Edge X-ray Absorption Spectroscopy of CrIII(acac)3 in Solution with Measured
and Calculated Absolute Absorption Cross Sections.
AB - X-ray absorption spectroscopy at the L-edge of 3d transition metals is widely
used for probing the valence electronic structure at the metal site via 2p-3d
transitions. Assessing the information contained in L-edge absorption spectra
requires systematic comparison of experiment and theory. We here investigate the
Cr L-edge absorption spectrum of high-spin chromium acetylacetonate CrIII(acac)3
in solution. Using a transmission flatjet enables determining absolute absorption
cross sections and spectra free from X-ray-induced sample damage. We address the
challenges of measuring Cr L absorption edges spectrally close to the O K
absorption edge of the solvent. We critically assess how experimental absorption
cross sections can be used to extract information on the electronic structure of
the studied system by comparing our results of this CrIII (3d3) complex to our
previous work on L-edge absorption cross sections of MnIII(acac)3 (3d4) and
MnII(acac)2 (3d5). Considering our experimental uncertainties, the most
insightful experimental observable for this d3(CrIII)-d4(MnIII)-d5(MnII) series
is the L-edge branching ratio, and we discuss it in comparison to semiempirical
multiplet theory and ab initio restricted active space calculations. We further
discuss and analyze trends in integrated absorption cross sections and correlate
the spectral shapes with the local electronic structure at the metal sites.
PMID- 29957943
TI - Machine Learning Adaptive Basis Sets for Efficient Large Scale Density Functional
Theory Simulation.
AB - It is chemically intuitive that an optimal atom centered basis set must adapt to
its atomic environment, for example by polarizing toward nearby atoms. Adaptive
basis sets of small size can be significantly more accurate than traditional atom
centered basis sets of the same size. The small size and well conditioned nature
of these basis sets leads to large saving in computational cost, in particular in
a linear scaling framework. Here, it is shown that machine learning can be used
to predict such adaptive basis sets using local geometrical information only. As
a result, various properties of standard DFT calculations can be easily obtained
at much lower costs, including nuclear gradients. In our approach, a rotationally
invariant parametrization of the basis is obtained by employing a potential
anchored on neighboring atoms to ultimately construct a rotation matrix that
turns a traditional atom centered basis set into a suitable adaptive basis set.
The method is demonstrated using MD simulations of liquid water, where it is
shown that minimal basis sets yield structural properties in fair agreement with
basis set converged results, while reducing the computational cost in the best
case by a factor of 200 and the required flops by 4 orders of magnitude. Already
a very small training set yields satisfactory results as the variational nature
of the method provides robustness.
PMID- 29957944
TI - Synthesis and Characterization of the First Borosulfates of Magnesium, Manganese,
Cobalt, Nickel, and Zinc.
AB - The first magnesium, manganese, cobalt, nickel, and zinc borosulfates were
synthesized employing solvothermal conditions starting from the superacid
H[B(HSO4)4] and the respective metal powders (Mg, Ni, Zn) or oxides (MnO2, CoO).
alpha- M4[B2O(SO4)6] ( M = Mg, Mn, Co, Ni, Zn) crystallize isotypically in a new
structure type in P3 (No. 147) with Z = 1, a = 793.59(4)-810.86(9) pm, and c =
743.98(4)-775.09(9) pm. The oligomeric anion comprises unprecedented dimeric open
branched quadruple tetrahedra { oB, 4 t}[B2O(SO4)6]8-, which are connected via
M2O9 dimers to give a three-dimensional network. Upon mild heating, we observed a
phase change from alpha-Mg4[B2O(SO4)6] to beta-Mg4[B2O(SO4)6], yielding a further
new structure type in P3 (No. 147) with Z = 3, a = 1391.96(6) pm, and c =
748.54(3) pm. The reaction of MgB2 with SO3 yields Mg[B2(SO4)4] crystallizing in
C2/ c with Z = 4, a = 1744.28(10) pm, b = 531.45(3) pm, c = 1429.06(8) pm, and
beta = 126.323(2) degrees showing phyllosilicate topology. UV/vis spectroscopy
on alpha- TM4[B2O(SO4)6] ( TM = Co, Ni) confirms the valence state of the TM and
reveals that borosulfates are weakly coordinating host structures. Structure
relationships between the presented crystal structures and similar borophosphates
are shown. The results of vibrational spectroscopy as well as magnetic and
thermal measurement investigations are discussed.
PMID- 29957945
TI - Green's Function Coupled-Cluster Approach: Simulating Photoelectron Spectra for
Realistic Molecular Systems.
AB - In this paper, we present an efficient implementation for the analytical energy
dependent Green's function coupled-cluster with singles and doubles (GFCCSD)
approach with our first practice being computing spectral functions of realistic
molecular systems. Because of its algebraic structure, the presented method is
highly scalable and is capable of computing spectral function for a given
molecular system in any energy region. Several typical examples have been given
to demonstrate its capability of computing spectral functions not only in the
valence band but also in the core-level energy region. Satellite peaks have been
observed in the inner valence band and core-level energy region where a many-body
effect becomes significant and the single particle picture of ionization often
breaks down. The accuracy test has been carried out by extensively comparing the
computed spectral functions by our GFCCSD method with experimental photoelectron
spectra as well as the theoretical ionization potentials obtained from other
methods. It turns out the GFCCSD method is able to provide a qualitative or
semiquantitative level of description of ionization processes in both the core
and valence regimes. To significantly improve the GFCCSD results for the main
ionic states, a larger basis set can usually be employed, whereas the improvement
of the GFCCSD results for the satellite states needs higher-order many-body terms
to be included in the GFCC implementation.
PMID- 29957946
TI - Site-Specific Photodecomposition in Conjugated Energetic Materials.
AB - Nonadiabatic excited-state molecular dynamics (NEXMD) has been used to study
photodecomposition in a class of recently synthesized bicyclic conjugated
energetic materials (CEMs) composed of fused tetrazole and tetrazine derivatives
with increasing oxygen substitutions. Modification by oxygen functionalization
has already been demonstrated to increase the two-photon absorption intensity in
the target CEMs while simultaneously improving oxygen balance. Photodecomposition
mechanisms in materials that undergo nonlinear absorption could be used to
achieve controlled, direct optical initiation. Here, we use NEXMD simulations to
model the nonradiative relaxation and photodecomposition in CEMs following
photoexcitation by a simulated Nd:YAG laser pulse. Excess electronic energy is
quickly converted into vibrational energy on a sub-100 fs time scale resulting in
bond dissociation. We find that, for the studied tetrazine derivatives, the
bicyclic framework is an important structural feature that enhances the
photochemical quantum yield and the high atomic oxygen content increases the
relaxation lifetime and opens additional photodissociation pathways targeting the
oxygen-substituted sites. The presented analysis scheme based on bond orders in
the swarm of NEXMD trajectories is a useful tool for determining photochemical
reactions.
PMID- 29957947
TI - Study of Methylidyne Radical (CH and CD) Reaction with 2,5-Dimethylfuran Using
Multiplexed Synchrotron Photoionization Mass Spectrometry.
AB - At 298 K the reactions of 2,5-dimethlyfuran + CH(X2Pi) and + CD radicals were
investigated using synchrotron radiation coupled with multiplexed photoionization
mass spectrometry at the Lawrence Berkeley National Laboratory. Reaction products
were characterized based on their photoionization spectra and kinetic time
traces. The CBS-QB3 level of theory was used for all energy calculations, and
potential energy surface scans were used to determine thermodynamically favorable
reaction mechanisms. The two entrance pathways observed in the reactions are CH
insertion within the C-O bond and CH addition to the pi-bond system. Both yield
initial 6-membered ring radical intermediates. Primary products from the CH
addition pathway were observed at m/ z = 108, 66, and 42. The two C7H8O isomers
at m/ z = 108 formed are 1,2,4-heptatrien-6-one and 3-hepten-5-yne-2-one. At m/ z
= 66, the three C5H6 isomers observed are 1,3-cyclopentadiene, 3-penten-1-yne
(E), and 1-pent-4-yne. Ketene ( m/ z = 42) is also observed. From CH insertion
entrance channel, the three C6H8 isomers produced are 1,2,4-hexatriene (Z), 2
hexen-4-yne (E), and 1,3,4-hexatriene. Patterns of H-loss, CHO-loss, and CO-loss
observed were also in agreement with trends observed in other similar studies. H
assisted isomerization pathways have been considered as well for the formation of
m/ z = 66, 80, and 108 isomers.
PMID- 29957948
TI - Metabolic Demethylation and Oxidation of Caffeine during Uptake by Lettuce.
AB - Pharmaceuticals can be metabolized after being taken up by plants. The
metabolites could manifest similar or equivalent bioactivity to the parent
compound, promoting the critical need to understand the metabolism in plants.
Caffeine has been frequently detected in agriculture produce; however, little
attention is given to its metabolites in vegetables. This study examined uptake
and metabolism of caffeine in lettuce in a hydroponic system. Caffeine and its
metabolites in aqueous solution and lettuce were identified and quantified using
a liquid chromatography coupled to a QTrap tandem mass spectrometry instrument.
After 144 h, over 50% of applied caffeine dissipated in the hydroponic lettuce
system, and eight caffeine metabolites were identified primarily in the shoots.
Caffeine underwent demethylation reactions, which were confirmed with authentic
standards, and the total amount accounted for 20% of the initially applied
caffeine. Other metabolism pathways included oxidation and hydroxylation, and the
amount of metabolites increased over uptake time.
PMID- 29957949
TI - Induction Heating Efficiency of Water-Dispersible Mn0.5Fe2.5O4@YVO4:Eu3+ Magnetic
Luminescent Nanocomposites in an Acceptable ac Magnetic Field: Hemocompatibility
and Cytotoxicity Studies.
AB - Not many reports are available on magnetic-luminescent nanocomposites for cancer
hyperthermia applications. Further, such nanocomposites on Mn2+-doped iron oxide
may be available rather rarely. Studies on the induction heating properties
within the threshold magnetic field and frequency factors are still rare. In most
cases, magnetic nanoparticles are studied for hyperthermia and lanthanide-doped
luminescent nanoparticles for certain biomedical applications. Here, we report on
water-dispersible superparamagnetic manganese-doped iron oxide (Mn0.5Fe2.5O4)
nanoparticles and a polyethylene glycol6000-coated magnetic-luminescent
nanocomposite. The nanocomposite is composed of magnetic Mn0.5Fe2.5O4 (average
size 10-20 nm) nanoparticles and red-emitting YVO4:Eu3+ (average size 40-50 nm)
nanoparticles. These magnetic nanoparticles and nanocomposites are studied for
their induction heating abilities at different acceptable Hf values ( H, strength
of alternating magnetic field and f, the operating frequency). The operational Hf
values lie in the ranges of 2.15 * 106 to 4.58 * 106 kA m-1 s-1 that are well
below the threshold limit of 5 * 106 kA m-1 s-1. A specific absorption rate as
high as 132 and 63 W/g, respectively, for Mn0.5Fe2.5O4 and
Mn0.5Fe2.5O4@YVO4:Eu3+, can be achieved. The rate of heating and the temperature
achieved with time can be tuned with concentrations as well as magnetic
constituents in the nanocomposites. Hemocompatibility analysis revealed high
blood compatibility with <5% hemolysis. The cytotoxicity analysis in the MCF-7
cell line showed that the cell viability is 74-85% for 0.2-0.5 mg of the magnetic
luminescent nanocomposites. Beyond this concentration, the percentage of cell
death is very high. The red-emitting magnetic-luminescent nanocomposites will be
useful for in vitro optical imaging and tracking of magnetic nanoparticles. The
magnetization analysis showed that the samples have high enough saturation
magnetization and low residual magnetization, which is quite suitable for
clinical applications. The water dispersibility, hemocompatibility, and
cytotoxicity assay in conjunction with their efficient induction heating
abilities have shown that these magnetic-luminescent nanocomposites will have
potential applications in magnetic fluid hyperthermia and optical imaging.
PMID- 29957950
TI - Storage of Micellar Casein Powders with and without Lactose: Consequences on
Color, Solubility, and Chemical Modifications.
AB - During storage, a series of changes occur for dairy powders, such as protein
lactosylation and the formation of Maillard reaction products (MRPs), leading to
powder browning and an increase of insoluble matter. The kinetics of protein
lactosylation and MRP formation are influenced by the lactose content of the
dairy powder. However, the influence of lactose in the formation of insoluble
matter and its role in the underlying mechanisms is still a subject of
speculation. In this study, we aim to investigate the role of lactose in the
formation of insoluble matter in a more comprehensive way than the existing
literature. For that, two casein powders with radically different lactose
contents, standard micellar casein (MC) powder (MC1) and a lactose-free (less
than 10 ppm) MC powder (MC2), were prepared and stored under controlled
conditions for different periods of time. Powder browning index measurements and
solubility tests on reconstituted powders were performed to study the evolution
of the functional properties of MC powders during aging. Proteomic approaches
[one-dimensional electrophoresis and liquid chromatography-mass spectrometry (LC
MS)] and innovative label-free quantification methods were used to track and
quantify the chemical modifications occurring during the storage of the powders.
Reducing the amount of lactose limited the browning of MC powders but had no
effect on the loss of solubility of proteins after storage, suggesting that the
action of lactose, leading to the production of MRC, does not promotes the
formation of insoluble matter. Electrophoresis analysis did not reveal any links
between the formation of covalent bonds between caseins and loss in solubility,
regardless of the lactose content. However, LC-MS analyses have shown that
different levels of chemical modifications occur during the MC powder storage,
depending upon the presence of lactose. An increase of protein lactosylation and
acetylation was observed for the powder with a higher lactose content, while an
increase of protein deamidation and dephosphorylation was observed for that
containing lower lactose. The decrease of pH in the presence of lactose as a
result of Maillard reaction (MR) may explain the difference in the chemical
modifications of the two powders. In view of the present results, it is clear
that lactose is not a key factor promoting insolubility and for the formation of
cross-links between caseins during storage. This suggests that lactosylation is
not the core reaction giving rise to loss in solubility.
PMID- 29957951
TI - Using a Vegetative Environmental Buffer to Reduce the Concentrations of Volatile
Organic Compounds in Poultry-House Atmospheric Emissions.
AB - Ground-level ozone is formed when volatile organic compounds (VOCs) react with
hydroxyl radicals and nitrogen oxides in the presence of ultraviolet light.
Research has typically focused on the release and control of VOCs from
hydrocarbon processing; however, agricultural activities, such as poultry
production, can also be VOC sources and potentially contribute to ozone
pollution. Therefore, this study examines the emission of C2-C6 VOCs from poultry
houses and the use of a vegetative environmental buffer (VEB) as a potential
mitigation strategy. Sampling campaigns were conducted at two farms, one with and
one without a VEB. Of the nine compounds measured, methanol, ethanol, and acetone
were the primary VOCs emitted and had the largest ozone-formation potential
(OFP). A significantly larger decrease in the OFP for methanol as a function of
distance from the poultry house was observed at the farm with the VEB as compared
with at the farm without the VEB. These results suggest that besides being a
visual barrier and particulate screen, VEBs can provide some control of VOCs
emitted from poultry production.
PMID- 29957952
TI - Positron-Emission Tomography of HER2-Positive Breast Cancer Xenografts in Mice
with 89Zr-Labeled Trastuzumab-DM1: A Comparison with 89Zr-Labeled Trastuzumab.
AB - Our aim was to synthesize 89Zr-labeled trastuzumab-emtansine (89Zr-DFO-T-DM1) to
probe the delivery of trastuzumab-emtansine (T-DM1) to HER2-positive breast
cancer (BC) by positron emission tomography (PET). We further aimed to compare
the tumor and normal tissue uptake of 89Zr-DFO-T-DM1 with 89Zr-DFO-trastuzumab. T
DM1 was modified with 3.0 +/- 0.2 desferrioxamine (DFO) chelators for complexing
89Zr by reaction with a 14-fold molar excess of p-NCS-Bz-DFO. The number of DFO
chelators per T-DM1 molecule was quantified spectrophotometrically at 430 nm
after the reaction with FeCl3. SDS-PAGE and SE-HPLC demonstrated a pure and
homogeneous immunoconjugate. DFO-T-DM1 and DFO-trastuzumab were labeled to high
efficiency (>97%) with 89Zr at a specific activity of 0.55 MBq/MUg in a 2 M
Na2CO3/0.5 M HEPES buffer, pH 7.0, at RT for 60-90 min. The labeling efficiency
was measured by instant thin layer-silica gel chromatography (ITLC-SG) and SE
HPLC. HER2 immunoreactivity was measured in a saturation binding assay using SK
BR-3 human BC cells. 89Zr-DFO-T-DM1 exhibited high affinity HER2 binding ( Kd =
3.7 +/- 0.4 nM) that was not significantly different than 89Zr-DFO-trastuzumab
(4.4 +/- 0.5 nM; P = 0.06). The optimal time for tumor imaging with 89Zr-DFO-T
DM1 was 96 h post-injection in NOD-scid mice with s.c. HER2 overexpressing (HER2
3+) BT-474 human BC xenografts. Tumor uptake was dependent on the level of HER2
expression in mice with s.c. BT-474 (HER2 3+), MDA-MB-231/H2N (HER2 2+), MDA-MB
231 (HER2 0-1+), or MDA-MB-468 (HER2 0) human BC xenografts injected with 89Zr
DFO-T-DM1 (10 MUg, 5.2 MBq). All tumors were visualized by microPET/CT, but the
tumor intensity was greatest for BT-474 and MDA-MB-231/H2N xenografts. The tumor
uptake of 89Zr-DFO-T-DM1 was 4.1-fold significantly higher than 89Zr-DFO
trastuzumab in mice with s.c. BT-474 (HER2 3+) xenografts (43.5 +/- 4.3%ID/g vs
10.6 +/- 5.4%ID/g, respectively; P < 0.001). Tumor uptake of 89Zr-DFO-T-DM1 in
MDA-MB-231/H2N xenografts (HER2 2+) was 3.7-fold significantly higher than 89Zr
DFO-trastuzumab (10.1 +/- 3.6%ID/g vs 2.7 +/- 0.5%ID/g; P < 0.001). The higher
tumor uptake of 89Zr-DFO-T-DM1 compared to 89Zr-DFO-trastuzumab was not due to a
higher HER2 binding affinity or to differences in the residence time in the blood
or tumor size. We conclude that 89Zr-DFO-T-DM1 is a useful probe to assess the
delivery of T-DM1 to HER2-positive BC. PET with 89Zr-DFO-trastuzumab has been
studied clinically to predict response to T-DM1, but our results suggest that
89Zr-DFO-T-DM1 may be more accurate due to the differences in the tumor uptake
observed in the preclinical BC xenograft mouse models.
PMID- 29957953
TI - Bioinspired Poly(vinylidene fluoride) Membranes with Directional Release of
Therapeutic Essential Oils.
AB - Here, the morphology of polypore fungi has inspired the fabrication of
poly(vinylidene fluoride) (PVDF) membranes with dual porosity by nonsolvent
induced phase separation (NIPS). The fruiting body of such microorganisms is
constituted of two distinct regions, finger- and sponge-like structures, which
have been successfully mimicked by controlling the coagulation bath temperature
during the NIPS process. The use of water at 10 degrees C as coagulant resulted
in membranes with the highest finger-like/sponge-like ratio (53% of the total
membrane thickness), while water at 90 degrees C allowed the formation of
macrovoid-free membranes. The microchannels and the asymmetric porosity were used
to enhance the oil sorption capacity of the PVDF membranes and to achieve
directional release of therapeutic essential oils. These PVDF membranes with
easily tuned asymmetric channel-like porosity and controlled pore size are ideal
candidates for drug delivery applications.
PMID- 29957954
TI - 7-Hydroxy- N-Methylquinolinium Chromophore: A Photolabile Protecting Group for
Blue-Light Uncaging.
AB - The development of the N-methyl-7-hydroxymethylquinolinium ( N-Me-7-HQm) caging
chromophore as a novel visible-light-sensitive photolabile protecting group is
described. N-Me-7-HQm-caged compounds can be photoactivated by blue-light
emitting diode (LED) light (458 nm) with high photolytic efficiency, supporting
applications to caging chemistry, and they also have sufficient water solubility
and high resistance to spontaneous hydrolysis.
PMID- 29957955
TI - Effect of Formulation Additives on Drug Transport through Size-Exclusion
Membranes.
AB - The aim of this research was to investigate the driving force of membrane
transport through size-exclusion membranes and to provide a concentration-based
mathematical description of it to evaluate whether it can be an alternative for
lipophilic membranes in the formulation development of amorphous solid
dispersions. Carvedilol, an antihypertensive drug, was chosen and formulated
using solvent-based electrospinning to overcome the poor water solubility of the
drug. Vinylpyrrolidone-vinyl acetate copolymer (PVPVA64) and Soluplus were used
to create two different amorphous solid dispersions of the API. The load
dependent effect of the additives on dissolution and permeation through
regenerated cellulose membrane was observed by a side-by-side diffusion cell,
MUFLUX. The solubilizing effect of the polymers was studied by carrying out
thermodynamic solubility assays. The supersaturation ratio (SSR, defined as the
ratio of dissolved amount of the drug to its thermodynamic solubility measured in
exactly the same medium) was found to be the driving force of membrane transport
in the case of size-exclusion membranes. Although the transport through
lipophilic and size-exclusion membranes is mechanistically different, in both
cases, the driving force of membrane transport in the presence of polymer
additives was found to be the same. This finding may enable the use of size
exclusion membranes as an alternative to lipid membranes in formulation
development of amorphous solid dispersions.
PMID- 29957956
TI - CD44-Targeted Polymer-Paclitaxel Conjugates to Control the Spread and Growth of
Metastatic Tumors.
AB - One of the greatest challenges in cancer therapy is to control metastatic spread,
seeding, and growth of tumors in distant organs. Recently, we reported on the
design of a novel "drug-free" therapeutic copolymer bearing the antimigratory
A5G27 peptide, designated P-(A5G27)-FITC, that shows excellent specificity to
cancer cells overexpressing CD44v3 and CD44v6 and inhibits cancer cell migration
and invasion. We demonstrated that P-(A5G27)-FITC accumulated preferentially in
subcutaneous (sc) implanted 4T1 tumors following parenteral administration.
Moreover, we showed that pretreatment of mice with P-(A5G27)-FITC prior to 4T1
cell inoculation inhibited colonization of circulating 4T1 cells in the lungs. In
this study, we designed a new polymer-peptide-drug conjugate to inhibit
vigorously growing primary tumors and control invasive behavior of cancer cells.
To this end, the antimitotic drug (paclitaxel, PTX) was conjugated to P-(A5G27)
FITC. The targeted polymer-drug conjugate (P-(A5G27)-PTX) was significantly more
toxic toward CD44-overexpressing cancer cells than the nontargeted copolymer. In
vivo, a single iv injection of P-(A5G27)-PTX prolonged the survival of C57BL/6
mice with established B16-F10 lung metastases. When injected intraperitoneally
into BALB/c mice implanted sc with 4T1 tumors, P-(A5G27)-PTX significantly
decreased the rate of primary tumor growth, increased the median survival of
mice, and reduced the number of 4T1 metastases in the lungs when compared to
nontargeted copolymer. Most interestingly, the CD44-targeted "drug-free"
copolymer P-(A5G27) (without PTX) significantly inhibited the rate of tumor
growth and further prolonged the median survival time of mice to the same extent
as the PTX-containing formulations (P-(A5G27)-PTX or free PTX). Overall, this
study highlights the therapeutic potential of the HPMA copolymer-A5G27 conjugates
("drug-free" and PTX-bearing copolymers) to control the metastatic spread of
cancer.
PMID- 29957957
TI - Phase Separation and Stack Alignment in Aqueous Cellulose Nanocrystal Suspension
under Weak Magnetic Field.
AB - Isotropic-nematic (I-N) transitions in cellulose nanocrystal (CNC) suspension and
self-assembled structures in the isotropic and nematic phases were investigated
using scattering and microscopy methods. A CNC suspension with a mass fraction of
7.4% spontaneously phase separated into an isotropic phase of 6.9% in the top
layer and a nematic phase of 7.9% in the bottom layer. In both the phases, the
CNC particles formed stacks with an interparticle distance being of ~37 nm. One
dimensional small-angle neutron scattering (SANS) profiles due to both phases
could be fitted using a stacking model considering finite particle sizes. SANS
and atomic force microscopy studies indicate that the nematic phase in the bottom
layer contains more populations of larger particles. A weak magnetic field of
~0.5 T was able to induce a preferred orientation of CNC stacks in the nematic
phase, with the stack normals being aligned with the field (perpendicular to the
long axis of CNC particles). The Hermans orientation parameter, ? P2?, was ~0.5
for the nematic phase; it remained unchanged during the relaxation process of ~10
h. The fraction of oriented CNC populations decreased during the relaxation;
dramatic decrease occurred in the first 3 h. The top layer remained isotropic in
the weak field. Polarized microscopy studies revealed that the nematic phase was
chiral. Adjacent particles in a stack form a twisting angle of ~0.6 degrees ,
resulting in a helix pitch distance of ~22 MUm.
PMID- 29957958
TI - Site-Specific Hydrogen Exchange in a Membrane Environment Analyzed by Infrared
Spectroscopy.
AB - Hydrogen exchange is a powerful method to examine macromolecules. In membrane
proteins, exchange can distinguish between solvent-accessible and -inaccessible
residues due to shielding by the hydrophobic environment of the lipid bilayer.
Herein, rather than examining which residues undergo hydrogen exchange, we employ
a protocol that enables the full deuteration of all polar hydrogens in a membrane
protein. We then measure the impact of hydrogen exchange on the shift of the
amide I vibrational mode of individually labeled sites. The results enable us to
correlate polarity with vibrational shifts, thereby providing a powerful tool to
examine specific locations within a membrane protein in its native membrane
environment.
PMID- 29957959
TI - Solvent Effects on Tuning Pore Structures in Polyimide Aerogels.
AB - This work evaluates the effects of solvents and a block copolymer surfactant on
pore structures in polyimide aerogels synthesized via sol-gel reaction process.
Specifically, cross-linked polyimide gel networks are synthesized in single or
mixed solvents from a combination of dimethylformamide, N-methylpyrrolidone, and
dimethylacetamide and supercritically dried to obtain aerogels. The bulk density,
pore size, and mechanical properties of aerogels are determined. The results show
that gel times are strongly dependent on the electron acceptance ability of the
solvent system and concentration of the surfactant. At longer gel times, the
polyimide strands coarsen and the pores in aerogel shift from predominantly
mesoporous to macroporous state with corresponding reduction in compressive
modulus. The block copolymer surfactant also slows down gelation and coarsens the
polyimide strands but only weakly affects the compressive modulus of the
aerogels.
PMID- 29957960
TI - Pulse Radiolysis of TIPS-Pentacene and a Fluorene-bridged Bis(pentacene):
Evidence for Intramolecular Singlet-Exciton Fission.
AB - Exposing TIPS-pentacene in deaerated benzene to ionizing radiation generates a
mixture of singlet- and triplet-excited states of the solute. The singlet
undergoes radiative decay without spin conversion whereas the triplet undergoes
radiationless decay on the microsecond time scale. The concentration of each
species was established by dosimetry. The excited-singlet state is not observed
on the nanosecond-time scale for a related fluorene-bridged bis(pentacene), but
the triplet is present in high concentration. Failure to detect the excited
singlet state is attributed to fast intramolecular singlet-exciton fission (iSEF)
which is found to produce two triplet species. A short-lived intermediate (tauT =
145 ns) is identified as the species (T_T) having both pentacene units present as
triplet states. The second transient is longer lived (tauT = 7.5 MUs) and is
assigned to the corresponding species (T_G) with a single pentacene promoted to
the triplet level. Dosimetry is used to conclude that iSEF partitions
overwhelmingly in favor of T_G (70%) relative to T_T (25%). The total triplet
yield from iSEF, therefore, is ca. 120% in this system, where the pentacene
terminals are weakly coupled.
PMID- 29957961
TI - Vibrationally Assisted Intersystem Crossing in Benchmark Thermally Activated
Delayed Fluorescence Molecules.
AB - Electrically injected charge carriers in organic light-emitting devices (OLEDs)
undergo recombination events to form singlet and triplet states in a 1:3 ratio,
representing a fundamental hurdle for achieving high quantum efficiency. Dopants
based on thermally activated delayed fluorescence (TADF) have emerged as
promising candidates for addressing the spin statistics issue in OLEDs. In these
materials, reverse singlet-triplet intersystem crossing (rISC) becomes efficient,
thereby activating luminescence pathways for weakly emissive triplet states.
However, despite a growing consensus that torsional vibrations facilitate spin
orbit-coupling- (SOC-) driven ISC in these molecules, there is a shortage of
experimental evidence. We use transient electron spin resonance and theory to
show unambiguously that SOC interactions drive spin conversion and that ISC is a
dynamic process gated by conformational fluctuations for benchmark carbazolyl
dicyanobenzene TADF emitters.
PMID- 29957962
TI - Construction of 1,3-Dithio-Substituted Tetralins by [1,5]-Alkylthio Group
Transfer Mediated Skeletal Rearrangement.
AB - A novel skeletal rearrangement involving a [1,5]-alkylthio group
transfer/cyclization sequence is described. Treatment of benzylidene malonates
having a thioketal moiety at the homobenzyl position with a catalytic amount of
Sc(OTf)3 afforded alkylthio group rearranged adducts in good chemical yields.
Detailed investigation of the reaction mechanism revealed that an intramolecular
conjugate addition/ring opening sequence (not through-space transfer) is the key
to achieving this reaction.
PMID- 29957963
TI - Seeded Emulsion Polymerization of Styrene in the Presence of Water-Swollen
Hydrogel Microspheres.
AB - In a previous study, we have ascertained that the charge distribution in hydrogel
microspheres (microgels) plays a crucial role in controlling the nanocomposite
structure of the polystyrene obtained from the seeded emulsion polymerization
(SEP) of styrene in the presence of microgels. However, all these polymerizations
were conducted at high temperature, where most of these microgels were dehydrated
and deswollen. In the present study, we initially verified that the nanocomposite
microgels can be synthesized even when the seed microgels are swollen and
hydrated during the SEP of styrene. These highly swollen microgels were used as
the nucleation sites for the polystyrene, and subsequently the propagation of the
hydrophobic polystyrenes proceeded within water-swollen microgels.
PMID- 29957964
TI - Asymmetric Total Syntheses of Insulicolide A, 14- O-Acetylinsulicolide A,
6beta,9alpha-Dihydroxy-14- p-nitrobenzoylcinnamolide, and 7alpha,14-Dihydroxy
6beta- p-nitrobenzoylconfertifolin.
AB - Asymmetric total syntheses of insulicolide A, 14- O-acetylinsulicolide A,
6beta,9alpha-dihydroxy-14- p-nitrobenzoyl cinnamolide, and 7alpha,14-dihydroxy
6beta- p-nitrobenzoylconfertifolin have been achieved for the first time. The key
steps in the synthesis include: (1) an iridium-catalyzed enantioselective polyene
cyclization to construct the drimane core bearing two all-carbon quaternary
chiral centers at C4 and C10 and (2) a cascade ozonolysis of the phenol ring to
form the lactone fragment of the target molecules.
PMID- 29957965
TI - On the Oblique Impact Dynamics of Drops on Superhydrophobic Surfaces. Part II:
Restitution Coefficient and Contact Time.
AB - We tested oblique drop impacts on a superhydrophobic surface at normal Weber
numbers ( Wen) in the range of 3-45, and at varying angles of incidence (AOIs),
ranging from 0 degrees (normal impact) to 60 degrees (highly oblique). Our
objective is to define the influence of the AOI on the restitution coefficient
and on the contact time of rebounding droplets. To interpret the overall
restitution coefficient of oblique drop rebounds (epsilon), we decoupled it into
two separate components: a normal (epsilonn) and a tangential restitution
coefficient (epsilont). We discovered that, regardless of the impact angle,
epsilonn can be accurately predicted as a function of the normal Weber number
(epsilonn = 0.94 Wen-1/4). We support this finding with a mathematical derivation
from theory, indicating a general scaling relationship of epsilonn ~ Wen-1/4 for
the normal restitution coefficient. Likewise, the tangential restitution
coefficient (epsilont) can also be predicted as a function of Wen (epsilont =
1.20 Wen-0.12) but is much larger than epsilonn. As a result, the overall
restitution coefficient (epsilon) increases for more oblique impacts because most
of the tangential velocity is preserved. Furthermore, using the observed
correlations for epsilonn and epsilont, we derived a model to predict the overall
restitution coefficient of rebounding drops at any Wen and AOI. The model's
predictions are highly accurate, lying close to our experimental observations in
all cases. Regarding the contact time ( tc), we found that for normal impacts, tc
increased slightly as Wen was raised. We associate this behavior with partial
penetration of the liquid into the surface's pores, which results in greater
solid-liquid adhesion, prolonging detachment. For highly oblique impacts (AOI =
60 degrees ), we observed the reverse trend: the drop's contact time decreases
for higher- Wen impacts. We attribute this correlation to stretched rebounding
behavior, which accelerates the rebounding of highly oblique impacts.
PMID- 29957966
TI - The Reliability and Validity of the Three Modified Versions of the Children's
Fear Survey Schedule-Dental Subscale of 9-12 Year Old Children in a Clinical
Setting in Bosnia and Herzegovina.
AB - OBJECTIVE: This study sought to obtain a comprehensive, reliable and valid
instrument for evaluation of the presence of dental fear and anxiety (DFA) in
children, through evaluation of the reliability and validity of three modified
versions of the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS).
MATERIALS AND METHODS: The study sample comprised children aged 9, 10, 11 and 12
years. The first sample group (200 patients) filled in a modified version of the
CFSSDS scale, the second sample group (100 patients) filled in a short form of
the Dental Fear Survey Schedule, and the third sample group (100 patients) filled
in a short version of the CFSS-DS scale, prior to dental treatment, respectively.
In order to determine test-retest reliability, the 184 patients from the first
sample group filled in the modified version of the CFSS-DS scale again, prior to
their next scheduled dental appointment. RESULTS: The modified version of the
CFSS-DS scale had the best internal consistency reliability (alpha=0.907), as
well as validity results, compared to the other two instruments used. Test-retest
reliability was moderate (Intraclass correlation coefficient: 0.58). CONCLUSIONS:
Of the three psychometric instruments used for evaluation of DFA presence in
children, the modified version of the CFSS-DS scale showed the most clinically
adequate reliability and validity values. This study thus provides a new
psychometric instrument that should be considered for clinical use in evaluation
of DFA presence in 9-12 year-olds, in a clinical setting sample type of children.
PMID- 29957967
TI - The Incidence and Frequency of Various Causes of Angioedema in Emergency
Medicine.
AB - OBJECTIVE: Angioedema (AE) is a potentially life-threatening event. We
investigated the etiology of AE, with the emphasis on bradykinininduced
angioedema treatment in emergency medicine. METHODS: The retrospective study
included 237 patients with AE, who were examined and treated in two hospitals
(group A and B) in Croatia from 2009 to 2016. The location and duration of AE,
data about chronic diseases and treatment, potential causative agents (food,
drugs, insect bites and chemicals), physical examination data and the subsequent
treatment were analyzed. RESULTS: There was no statistical difference regarding
age or comorbidities but there was a statistically significant difference in
etiology between the groups (Chi-square, P=0.03). Renin-angiotensin-aldosterone
system (RAAS) blocker induced AE was the main cause of emergency attendance in
group A (37.5%) and among the leading causes in group B (18.8%). Bradykinin
induced AE (hereditary angioedema (HAE) and RAAS-AE) were the leading causes in a
total of 75 (31.5%) patients. RAAS-AE was treated with glucocorticoids and
antihistamines. HAE attacks in both groups (2/7 patients, 1.5/6%) were treated
with specific therapy. Other causes of AE in groups A/B were insect bites (15/23
patients, 13.5/20%), use of antibiotics/analgetics (11/17 patients, 9/15%),
gastroesophageal reflux disease (10/11 patients, 8/9%), neoplasms (5/6 patients,
4/5%) and idiopatic (32/31 patients, 26.5/26%). 21% of patients were
hospitalized. CONCLUSION: Bradykinin-mediated AE was the main cause of emergency
attendance associated with AE. Advances in the treatment of HAE, with case
reports of patients with RAAS-AE treated with C1 esterase inhibitor concentrate
or bradykinin receptor antagonist, may prove to be a new, reliable and
efficacious therapy option.
PMID- 29957968
TI - Legal and Ethical Aspects of Pain Management.
AB - : In this manuscript we presented legal and ethical aspects of pain management.
Pain is a global public health problem because the burden of acute and chronic
pain is considerable and is continuously increasing. It has been postulated that
pain management is a fundamental human right, and that health systems are obliged
to ensure universal access to pain management services. The suggestion that pain
management is a right was fuelled by ample evidence about inadequate treatment of
pain. Undertreatment and underprescribing in the context of pain can potentially
have serious legal consequences, including charges about negligence, elder abuse,
manslaughter and euthanasia. Multiple international declarations by professional
societies have outlined pain management as a core ethical duty in medicine.
Therefore, healthcare professionals need to be aware of multiple facets of pain
related ethics, including appraisal of patient's decision-making capacity. The
worldwide opioid crisis also calls for careful consideration of specific ethical
issues. Finally, healthcare workers need to be aware of the the risks associated
with promoting pain management as a human right because patients and their
caretakers can mistakenly perceive that they have right to total analgesia.
CONCLUSION: Patients do have the right to pain management, but patient rights
have limits, which may interfere with other competing rights, and also rights of
their physicians. Treatment of pain must be medically, ethically and economically
justified. Healthcare workers have an obligation to continuously improve their
knowledge about pain management, including medical, legal and ethical aspects of
pain.
PMID- 29957969
TI - Early Machine-Human Interface around Sepsis Severity Identification: From
Diagnosis to Improved Management?
AB - OBJECTIVE: To investigate the statistical measures of the performance of 2
interventions: a) early sepsis identification by a computerized sepsis "sniffer"
algorithm (CSSA) in the emergency department (ED) and b) human decision to
activate a multidisciplinary early resuscitation sepsis and shock response team
(SSRT). METHODS: This study used a prospective and historical cohort study design
to evaluate the performance of two interventions. INTERVENTION: A computerized
sepsis sniffer algorithm (CSSA) to aid in early diagnosis and a multidisciplinary
sepsis and shock response team (SSRT) to improve patient care by increasing
compliance with Surviving Sepsis Campaign (SSC) bundles. RESULTS: The CSSA
yielded a sensitivity of 100% (95% CI, 99.13-100%) and a specificity of 96.2%
(95% CI, 95.55-96.45%) to identifying sepsis in the ED (Table 1). The SSRT
resource was activated appropriately in 34.1% (86/252) of patients meeting severe
sepsis or septic shock criteria; the SSRT was inappropriately activated only
three times in sepsis-only patients. In 53% (134/252) of cases meeting criteria
for SSRT activation, the critical care team was consulted as opposed to
activating the SSRT resource. CONCLUSION: Our two-step machine-human interface
approach to patients with sepsis utilized an outstandingly sensitive and specific
electronic tool followed by more specific human decision-making.
PMID- 29957970
TI - Lung Cancer: Preventable Disease.
AB - : Objective of the paper is to present lung cancer as preventable disease based
on epidemiological, molecular and genomic data. Lung cancer is the most deadly
malignancy around the world, both in male and female population. Vast majority of
lung cancers (close to 90%) are directly caused by cigarette smoking, and thus
present one of the most preventable deadly disease in humanity. Analysis of
history of cigarette consumption and rise of lung cancer as world epidemics.
Review of efforts to fight tobacco epidemics and how it influences incidence and
prevalence of the lung cancer. Investigation of the effects of cigarette smoking
on health and economic status of Bosnia and Hercegovina. Tobacco epidemics and
lung cancer can be prevented. Goal is to exterminate cigarette smoking. That can
be achieved only concerted effort by members of family, patients themselves,
physicians, researchers, non-governmental organizations, political figures and
society as a whole. CONCLUSION: In country like Bosnia and Herzegovina first step
is to inform society about devastating effects of cigarette smoking. Best
practices already exist and initial goal should be to start using them.
PMID- 29957971
TI - Epidemiological, Clinical and Molecular Characterization of Human Brucellosis in
Bosnia and Herzegovina - An Ongoing Brucellosis Outbreak.
AB - OBJECTIVE: The aim of this study was to evaluate an ongoing outbreak of
brucellosis in southern region of Bosnia and Herzegovina (BIH) on the
epidemiological, clinical and molecular level. PATIENTS AND METHODS: This study
included 19 patients affected by brucellosis between 2015 and 2017, in Trebisevo
(BIH). Out of 19 patients, 16 were admitted to and treated at the Department of
Infectious diseases of the University Clinical Hospital Mostar, while three
patients were treated in ambulatory care setting. Epidemiological, clinical and
microbiological parameters were investigated. The Rose Bengal test (RBT) positive
sera were serologically confirmed by complement fixation test (CFT). We also
analyzed blood cultures, and isolates were additionally serotyped. Molecular
analyses were performed with Bruce-ladder multiplex polymerase chain reaction
(PCR) and multiple locus variable number of tandem repeat analysis of 16 loci
(MLVA-16) assay. RESULTS: Fifteen out of 19 patients had been professionally
exposed to the bacterium, while four patients acquired brucellosis without prior
contact with infected animals. In seven out of eight (87.5%) patients with
localized form of brucellosis, we detected significantly higher values of C
reactive protein (CRP) or erythrocyte sedimentation rate (P<0.001). B. melitensis
was isolated from 13/16 (81.3%) blood culture samples, and additionally serotyped
as biovar 3. Using MLVA16 assay, 11 isolates were genotyped. We observed complete
genotype matches among 8/11 B. melitensis isolates, while 3/11 isolates differed
in Bruce04 locus. CONCLUSION: Overall, our study confirms the usefulness of MLVA
16 method in the epidemiological and molecular research of brucellosis during
epidemic that, most likely, originated from the same source.
PMID- 29957972
TI - The Medical School of the Catholic University of Croatia: Principles, Goals,
Standards and Organization.
AB - : The aim of the study was to present the concept on which the School of Medicine
at the Catholic University of Croatia (CUC) will be established. The new School
will alleviate the shortage of physicians in Croatia and introduce an innovative
form of medical education focused on principles of patient-centered care and
social accountability. At the same time, the students will acquire all relevant
competencies and levels of knowledge, skills and attitudes that are required by
current evidence in medical education, European standards and guidelines for
quality assurance at higher education institutions. The four pillars of the CUC
Medical School are: 1) distributed medical education that involves health
institutions outside major medical centers, 2) the concept of transformative
learning, 3) teaching and practicing evidence-based medicine, and 4)
implementation of quality management principles supported by information
technology solutions for effective management of learning, research and practice.
The overall aim of the CUC School of Medicine is to educate and train physicians
capable of using best available medical evidence to deliver economically
sustainable healthcare that can improve equity and health outcomes in the
communities they serve, particularly those that are currently underserved.
CONCLUSION: The proposed programme is introducing an original system of modern
medical education that insists on developing humanistic aspects of medicine,
patient-centred care and social accountability, while maintaining all
competencies and knowledge levels that a physician should have according to the
current understanding of medical education.
PMID- 29957973
TI - Continuous Assessment as a Good Motivational Tool in Medical Education.
AB - OBJECTIVE: Continuous assessment tests influence the learning needs of medical
students at particular times but are also beneficial in scheduled learning, and
act as motivating tool. These tests drive them to study by developing competition
and optimism regarding the forthcoming result. This study has been designed to
evaluate the role of these tests for medical students by learning about their
motivation. METHODS: This study was conducted on 150 medical students. The
students selected a continuous testing system or a classical system. Those who
selected the continuous system had six assessment tests each, after completion of
a curriculum block, usually 45 days apart. The motivation of the students in both
the groups was assessed by asking them for their expected results just before the
final examination. Statistical analysis was performed using Superior Performance
Statistical Software (SPSS) version 20. RESULTS: The students' final results
showed that almost half of the students who adopted the continuous assessment
test system were successful and one third of those who did not adopt this system.
The comparison of the successful students showed that the expectation of the
students from the continuous assessment test system was high compared to the
students who were not in the continuous assessment test system (P<0.05), even
though the students in these groups had more or less similar actual marks
(P>0.05). The comparison of the expected and actual marks of the successful
students, of students who failed only one unit and of students who failed both
units, showed that all these students had the same expectation (P<0.05) from the
examination, although they had different actual marks (P>0.05). CONCLUSION: It
was concluded that continuous assessment is good for student motivation. A
support system matched with the individual needs of the students is suggested to
improve their efficiency to gain the full benefits from this system.
PMID- 29957974
TI - Complete Response of Metastatic Melanoma to Second Line Chemotherapy with
Paclitaxel and Carboplatin - Case Report.
AB - OBJECTIVE: We present a patient with metastatic melanoma who had a complete
response to second line chemotherapy with paclitaxel and carboplatin. CASE
REPORT: Metastatic melanoma is an aggressive cancer with poor prognosis and 10
year survival less than 10%. We present a patient with metastatic melanoma who
had a complete response to second line chemotherapy with paclitaxel and
carboplatin. CONCLUSION: Second line chemotherapy with paclitaxel and carboplatin
in the treatment of metastatic melanoma may yield effective results.
PMID- 29957975
TI - Lymphovenous Anastomoses Between Thoracic Duct and Azygos Vein in a Human
Cadaver: A Case Report.
AB - OBJECTIVE: The study adds valuable information regarding lymphovenous
communications between the thoracic duct and the azygos vein, which are very
rarely discovered during anatomical dissections and very few cases have been
mentioned worldwide. A detailed description of our findings and a brief review of
the relevant literature are also provided. CASE REPORST: In the current study,
two sizeable obliquely directed lymphovenous anastomoses between the thoracic
duct and the azygos vein at the midportion of the mediastinum are described in
the same cadaver. CONCLUSION: The existence of such anastomoses in humans, as
well in animals, is a scientific issue under debate. Cases of rapid cancer spread
could be potentially explained by the likely presence of the abovementioned
communications.
PMID- 29957976
TI - Spontaneous Intraparenchymal Lung Haematoma with Active Bleeding, Associated with
S. Aureus.
PMID- 29957977
TI - Medical Journals in Bosnia and Herzegovina from 1878 to 1945.
AB - : This paper presents the medical journals published in Bosnia and Herzegovina
(BIH) in the period from 1878 to 1945. The first medical journal in BIH may be
deemed to be Jahrbuch des Bosnisch-Hercegowinischen Landesspittales in Sarajevo
(The Yearbook of the National Hospital of Bosnia and Herzegovina in Sarajevo). In
a special part of this journal, doctors from Austro-Hungary serving in Sarajevo
wrote scholarly articles about their patients' various ailments. Up to 1945 seven
more medical journals were published in BIH: Trezvenost - Organ Jugoslavenskog
Saveza Trezvenosti (Temperance - the Journal of the Yugoslav Temperance Society),
Zdravlje - Lekarske pouke o zdravlju i bolesti (Health, Medical lessons on Health
and Disease), Glasnik Lekarske komore za Bosnu, Hercegovinu, Dalmaciju i Crnu
Goru (The Journal of the Chamber of Physicians of Bosnia, Herzegovina, Dalmatia
and Montenegro), Glasnik Lekarske komore Vrbaske banovine (Journal of the Chamber
of Physicians of Vrbaska banovina, Glasnik Lekarske komore Drinske banovine
(Journal of the Chamber of Physicians of Drinska banovina), Vjesnik Zavoda za
suzbijanje endemijskog sifilisa u Bosni i Hercegovini (Journal of the Institute
for Combatting Endemic Syphilis in Bosnia and Herzegovina) and Casopis za
medicinu i biologiju (Journal for Medicine and Biology). CONCLUSION: Medical
journals published in BIH in the period from 1878 to 1945 were published in times
marked by specific political and social circumstances in BIH, in the time when
BIH was not independent, and was under the influence of the health culture of the
ruling regimes. Most of the authors of the articles published in these journals
were citizens of the occupying authorities, although the papers published were
mainly the result of research undertaken in BIH.
PMID- 29957978
TI - The English Sweating Sickness: Out of Sight, Out of Mind?
AB - : In this paper we aim to add additional knowledge regarding the occurrence,
origin and epidemiological features of the English sweating sickness. The English
sweating sickness raged in five devastating epidemics with mortality rates
between 30 and 50% between 1485 and 1551 throughout England, and on one occasion
also affected mainland Europe, in 1529. The Picardy sweat, generally considered
as the English sweating sickness' lesser deadly successor, flared up in France in
1718 and caused 196 localized outbreaks with varying severity all over France and
neighboring countries up to 1861. The English sweating sickness has been the
subject of numerous attempts to define its origin, but so far all efforts have
failed due to lack of material, DNA or RNA, that - using modern techniques and
knowledge - could shed light on its cause. Although the time frame in which the
English sweating sickness occurred and the geographical spread of the outbreaks
is generally known, we will demonstrate here that there was more to it than meets
the eye. We found reports of cases of sweating sickness in years before, after
and between the 1485, 1508, 1517, 1529 and 1551 epidemics, as well as reports of
sweating sickness in Italy and Spain. CONCLUSION: In spite of the fact that the
English sweating sickness apparently has not caused casualties for a more than a
century now, we suggest that -given the right circumstances- the possibility of
re-emergence might still exist. The fact that up until today we have no
indication concerning the causal pathogen of the English sweating sickness is
certainly not re-assuring.
PMID- 29957979
TI - A Quarter Century of Emerging Infectious Diseases - Where Have We Been and Where
Are We Going?
AB - : A quarter century ago the landmark report from the U. S. National Academies of
Sciences, Engineering, and Medicine entitled "Emerging Infections, Microbial
Threats to Health in the United States" was released. This classic study captured
the societal changes then underway in our rapidly growing world: The growth of
the world's population and changing human behavior; the advances and
globalization of technology and industry; the changes in economic development and
land use; the dramatic increase in speed and frequency of international travel
and commerce; the adaptation of microbes and the appearance of never before seen
pathogens; and the breakdown of traditional public health measures. This societal
evolution has only increased and the growing frequency of outbreaks foretold in
the report has come to pass. Each new disaster has precipitated changes and
adaptations in our global response to infectious diseases designed to reduce
risks and avoid future outbreaks. We discuss these past events and how each led
to change in an effort to mitigate future threats. We also look to the future to
consider what challenges might lay ahead. CONCLUSION: Major outbreaks over the
past quarter century validated the concept of emerging infectious diseases and
led to improvements in global policies and national public health programs;
however, there will likely always be new diseases and the threat of reemergence
of diseases once thought controlled leading to a constant need for vigilance in
public health preparedness.
PMID- 29957980
TI - Pearls of Neonatal Intertrigo in Ancient Greek and Byzantine Medicine.
AB - OBJECTIVE: Confirmation of knowledge of neonatal intertrigo in ancient Greek and
Byzantine medicine. METHOD: A search of Thesaurus Linguae Graecae was conducted
with the following terms as key words, "syggama", "xyggauma", "paratrimma" and
"ektrimma". RESULTS: Ancient Greek medico-philosophers introduced therapeutic
measures based upon herbs and minerals, while a similar therapeutic approach was
also used by the Byzantines. Hippocrates of Kos (460-377) was among the first to
introduce written instructions, also proposing preventive treatment with
palliative and aromatic herbs. Cataplasms, thalassotherapy, and fumigation were
used, combined with hygienic measures in the affected area. Chalk powder was also
prescribed to absorb moisture. CONCLUSION: The main principles in the treatment
of intertrigo remain the same, celebrating the ancient Greeks' methodology and
rationalism.
PMID- 29957981
TI - The Hippocratic Method for the Reduction of the Mandibular Dislocation, an
Ancient Greek Procedure Still in Use in Maxillofacial Surgery.
AB - Mandibular dislocation remains an acute medical condition in maxillofacial
surgery. Since the Hippocratic era its reduction has been performed exactly in
the same way it is now performed in modern surgery. We report an example of an
elderly female patient with bilateral mandibular dislocation, who came to our
department and was treated under sedation using the Hippocratic bimanual
intraoral technique by two medical personnel, depicting the timeless usage of the
method. Although some characteristics of the procedure were wrongfully attributed
to others, such as Barton and Lewis, after a thorough examination of the ancient
Greek medical texts, its originality should in fact be attributed solely to the
Hippocratic School of Medicine. Furthermore, we recommend the use of the term
"mandibular dislocation" instead of the "temporomandibular joint dislocation", as
a more accurate medical definition.
PMID- 29957982
TI - Mechanism studies of Xinfeng capsule on improving cardiovascular function though
toll-like receptor 4/nuclear factor kappa B pathwayin a rat model of adjuvant
arthritis.
AB - OBJECTIVE: To observe the impact of Xinfeng capsule (XFC) on cardiovascular
function in adjuvantarthritis (AA) model rats and investigate the mechanism
though toll-like receptor 4 (TLR4)/nuclear factorkappa B (NF-kappaB) signaling
pathway. METHODS: Seventy rats were randomly divided into seven groups: normal
control (NC), model control(MC), tripterygium glycosides tablet (TPT),
methotrexate (MTX), high, moderate and low doseXFC group. The administration
began from day 19 after modeling for 30 day. Paw swelling, arthritic index(AI),
cardiac function indexes and myocardial pathological pattern were detected. The
expressionof TLR4, myeloid differentiation factor (MyD) 88, interleukin-1
receptor-associated kinase (IRAK) 1, tumornecrosis factor receptor associated
factor (TRAF) 6, NF-kappaB, tumor necrosis factor-alpha (TNF-alpha) proteins in
myocardial tissue were determined by western blot method. RESULTS: Paw swelling
and AI in MC group increased in MC group (P < 0.01), and decreased inhigh and
moderate dose XFC groups (P < 0.01 or P > 0.05). Left ventricular systolic
pressure (LVSP),left ventricular end-diastolic pressure (LVEDP), heart rate (HR)
were elevated in MC group (P <0.01), and +/- dp/dtmax and CI were reduced (P <
.01); while LVSP, LVEDP and HR declined and +/-dp/dtmax, CI improved in high dose
XFC group (P < 0.05 or P < 0.01). LVSP in high dose XFC group werereduced more
than other treatment groups (P < 0.05 or P < 0.01). The improvements on LVEDP,
dp/dt-max were superior to MTX and low dose XFC group, and the improvement on CI
was better thanlow dose XFC group (P < 0.05 or P < 0.01). Myocardial fibers
arranged irregular in MC group with intracellularedema and mitochondria damage.
The modifications on myocardial structural were shownin each treatment group, but
more prominent in TPT, high and moderate dose XFC group. The proteinsof TLR4,
MyD88, IRAK1, TRAF6, NF-kappaB, TNF-alpha were highly expressed in MC group, and
those proteinsdeclined in high and moderate dose XFC group (P < 0.05 or P <
0.01). High dose XFC groupwas superior to MTX and low dose XFC group on reducing
TLR4, NF-kappaB, TNF-alpha (P < 0.05). CONCLUSION: XFC can not only inhibit the
excessive activation of TLR4/NF-kappaB signaling pathwayand the increased
inflammatory mediators, but also reduce the damage of myocardial tissue and
cells.
PMID- 29957983
TI - Evaluation of the Protective Effect of NMDA/Non-NMDA Receptor Antagonists Against
Ethambutol Induced Retinal ToxicityUsing ERG in Wistar Rats.
AB - To study the protective effect of NMDA and non-NMDA receptor antagonists against
ethambutol (EMB)induced retinal toxicity in Wistar rats using flash
electroretinogram (ERG). Rats were randomized into fourgroups: Group-1 received
vehicle. Group-2 received oral EMB (200 mg/kg/day). Group-3 and 4 were fed
withoral EMB along with memantine (MEM) (1 mg/kg, ip) and trimetazidine (TMZ)
(3mg/kg, ip) respectively. Alltreatments were continued up to 28 days. ERG was
recorded at 0 and 21st day using green and white lights.Ethambutol and 2, 2'
ethylene diimino dibutyric acid (EDBA) levels were quantified in rat body fluids
andtissues using LC-MS/MS. A higher rate of rat mortality was observed between
21st and 28th day, 21st dayconsidered for ERG recording among groups. Ethambutol
did not cause any significant change in 'a'-waveamplitude of rat ERG but caused a
predictable decrease in 'b'-wave amplitude of the rat ERG on the 21stday.
Memantine treatment showed a significant (P=0.029) protection against the fall of
'b'-wave amplitudeon 21st day. Interestingly, we found that plasma levels of EMB
in memantine treated rats were significantlyreduced when compared to the positive
control group. Memantine reversed the effects of EMB on 'b'-waveof rat ERG
suggests its protective role. We suggest MEM may be considered as a possible
preventive treatment modality for EMB induced vision toxicity warranting further
clinical investigations.
PMID- 29957984
TI - Pharmacological Interventions for Vascular Targeting in Retinopathy of
Prematurity: An Experimental Study.
AB - Purpose: This study was conducted to evaluate the pharmacological interventions
to target vascular proliferation in the Retinopathy of Prematurity (ROP).
Methods: Protein Kinase C modulator (Bryostatin), tubulin polymerization
inhibitor (Dolastatin 10), antiVEGF (Bevacizumab) and a non-specific VEGF
inhibitor (Thalidomide) were screened in Retinopathy of Prematurity (ROP) model.
The retinal vasculature was evaluated by calculating the tortuosity indices of
vessels and electroretinography responses in terms of 'b' wave amplitude and was
recorded from ROP rats on postnatal Day 17 and Day 25. Results: Retinopathy was
seen in the form of tortousity of vessels at the posterior pole with arteries
being affected more than veins. Maximum reduction in tortousity of vessels and
the highest 'b' wave amplitude noted in bryostatin with a significant correlation
between the two. Conclusion: Bryostatin showed a potential anti-angiogenic effect
on the progression of ROP and may hold a promising future in the treatment of
ROP.
PMID- 29957985
TI - Perceptions of Post-graduate Students Towards M.D. Physiology Curriculum in
India.
AB - In India, the system of postgraduate (PG) medical education has suffered due to
long-term neglect. Acomprehensive review of the curriculum of PG courses has not
taken place for several decades. Whateverchanges have been made are marginal and
have had little overall impact. Inspite of societal need and dearthof
physiologist, there is an observation that there hardly any takers for M.D.
Physiology. The above factscompel the need into rethinking the training and
curriculum designing of M.D. Physiology curriculum in India.The aim of the
present study was to assess the perception of M.D. physiology students toward the
presentcurriculum which will help in gaining an insight in further curriculum
planning. A questionnaire based on theobjectives of M.D. Physiology curriculum
was administered to post-graduate students from different parts ofthe country.
The results showed that though the curriculum is addressing the teaching needs of
postgraduateM.D. Physiology students, it is not preparing them adequately as a
researcher.
PMID- 29957986
TI - Electrolyte Abnormalities in Cisplatin Based Chemotherapy.
PMID- 29957987
TI - Endocrinology Coverage in the Haryana EML (Essential Medicines List).
PMID- 29957988
TI - High Steroid Usage Among Reproductive-aged Farmers in Underserved Area in
Indonesia, Langkat, South Securai Village.
PMID- 29957989
TI - Enteric Glial Cells and Inflammatory Bowel Disease: Friend or Foe.
PMID- 29957990
TI - Self-Assembly of a Double Hydrophilic Block Glycopolymer and the Investigation of
Its Mechanism.
AB - We report the self-assembly of a double hydrophilic block glycopolymer (DHBG) via
hydrogen bonding and coordinate bonding. This DHBG, composed of
poly(ethylene)glycol (PEG) and glycopolymer, self-assembled into a well-defined
structure. The DHBG was prepared through the controlled radical polymerization of
trimethylsilyl-protected propargyl methacrylate using a PEG-based reversible
addition-fragmentation chain transfer reagent, followed by sugar conjugation
using click chemistry. The DHBG self-assembly capability was investigated by
transmission electron microscopy and dynamic light scattering. Interestingly, the
DHBG self-assembled into a spherical structure in aqueous solution. Hydrogen
bonding and coordinate bonding with Ca2+ were identified as the driving forces
for self-assembly.
PMID- 29957991
TI - Data Integration for the Assessment of Population Exposure to Ambient Air
Pollution for Global Burden of Disease Assessment.
AB - Air pollution is a leading global disease risk factor. Tracking progress (e.g.,
for Sustainable Development Goals) requires accurate, spatially resolved,
routinely updated exposure estimates. A Bayesian hierarchical model was developed
to estimate annual average fine particle (PM2.5) concentrations at 0.1 degrees *
0.1 degrees spatial resolution globally for 2010-2016. The model incorporated
spatially varying relationships between 6003 ground measurements from 117
countries, satellite-based estimates, and other predictors. Model coefficients
indicated larger contributions from satellite-based estimates in countries with
low monitor density. Within and out-of-sample cross-validation indicated improved
predictions of ground measurements compared to previous (Global Burden of Disease
2013) estimates (increased within-sample R2 from 0.64 to 0.91, reduced out-of
sample, global population-weighted root mean squared error from 23 MUg/m3 to 12
MUg/m3). In 2016, 95% of the world's population lived in areas where ambient
PM2.5 levels exceeded the World Health Organization 10 MUg/m3 (annual average)
guideline; 58% resided in areas above the 35 MUg/m3 Interim Target-1. Global
population-weighted PM2.5 concentrations were 18% higher in 2016 (51.1 MUg/m3)
than in 2010 (43.2 MUg/m3), reflecting in particular increases in populous South
Asian countries and from Saharan dust transported to West Africa. Concentrations
in China were high (2016 population-weighted mean: 56.4 MUg/m3) but stable during
this period.
PMID- 29957992
TI - Synthesizing a Genetic Sensor Based on CRISPR-Cas9 for Specifically Killing p53
Deficient Cancer Cells.
AB - Cancer is still one of the greatest medical challenges in the world. The p53
protein plays an important role in the process of cancer formation. In addition,
p53 is found as the most common mutant gene in cancers. Because of the central
role of p53 in oncology, it is necessary to construct effective sensors to detect
this protein. However, there are few methods to detect wild type p53 protein
(WTP53) or to distinguish the wild type and mutant p53 proteins. In our study, we
designed and constructed a p53 genetic sensor that detected the expression of
WTP53 in cells. Moreover, we combined the p53 sensor with diphtheria toxin using
the CRISPR-Cas9 system to construct a p53 genetic sensor that specifically killed
p53-deficient cells such as tumor cells. Our study therefore developed a new way
to treat cancers by using an available genetic sensor based on p53 protein.
PMID- 29957993
TI - Copper Binding Induces Polymorphism in Amyloid-beta Peptide: Results of
Computational Models.
AB - Amyloid-beta (Abeta) peptides are intrinsically disordered peptides, and their
aggregation is the hallmark of Alzheimer's disease development. The propensity of
the Abeta peptide to intermolecular interactions, the latter favoring different
types of oligomers and aggregated forms, has been the object of a huge number of
studies. Several facts are now established: the presence of large amount of d
block (M) ions (Zn, Cu, and Fe) in the aggregated forms; the 1:1 M/Abeta ratio
favors the formation of amorphous aggregates, with an aggregation rate lower than
that in the absence of such ions. In particular, statistical models describing
the interactions between copper and amyloid peptides are mandatory to explain the
relationship between neurodegeneration, copper dyshomeostasis, and overproduction
of reactive oxygen species, the latter event occurring with aging. In this work,
we show, by replica-exchange molecular dynamics simulations, that a copper ion
(Cu2+) bound as in the experimentally observed prevailing coordination enhances
the probability of closed structures that hinder the formation of extended
intermolecular hydrogen bonds that stabilize fibrillar ordered aggregated forms.
On the other hand, this effect enhances the catalytic role of the complex during
the lifetime of soluble forms.
PMID- 29957994
TI - Salen Complexes as Fire Protective Agents for Thermoplastic Polyurethane: Deep
Electron Paramagnetic Resonance Spectroscopy Investigation.
AB - The contribution of copper complexes of salen-based Schiff bases N, N'
bis(salicylidene)ethylenediamine (C1), N, N'-bis(4
hydroxysalicylidene)ethylenediamine (C2), and N, N'-bis(5
hydroxysalicylidene)ethylenediamine (C3) to the flame retardancy of thermoplastic
polyurethane (TPU) is investigated in the context of minimizing the inherent
flammability of TPU. Thermal and fire properties of TPU are evaluated. It is
observed that fire performances vary depending upon the substitution of the salen
framework. Cone calorimetry [mass loss calorimetry (MLC)] results show that, in
TPU at 10 wt % loading, C2 and C3 reduce the peak of heat release rate by 46 and
50%, respectively. At high temperature, these copper complexes undergo
polycondensation leading to resorcinol-type resin in the condensed phase and thus
acting as intumescence reinforcing agents. C3 in TPU is particularly interesting
because it delays significantly the time to ignition (MLC experiment). In
addition, pyrolysis combustion flow calorimetry shows reduction in the heat
release rate curve, suggesting its involvement in gas-phase action. Structural
changes of copper complexes and radical formation during thermal treatment as
well as their influence on fire retardancy of TPU in the condensed phase are
investigated by spectroscopic studies supported by microscopic and powder
diffraction studies. Electron paramagnetic resonance (EPR) spectroscopy was fully
used to follow the redox changes of Cu(II) ions as well as radical formation of
copper complexes/TPU formulations in their degradation pathways. Pulsed EPR
technique of hyperfine sublevel correlation spectroscopy reveals evolution of the
local surrounding of copper and radicals with a strong contribution of nitrogen
fragments in the degradation products. Further, the spin state of radicals was
investigated by the two-dimensional technique of phase-inverted echo-amplitude
detected nutation experiment. Two different radicals were detected, that is, one
monocarbon radical and an oxygen biradical. Thus, the EPR study permits to deeply
investigate the mode of action of copper salen complexes in TPU.
PMID- 29957995
TI - Structural and Kinetic Studies of the Effect of Guanine N7 Alkylation and Metal
Cofactors on DNA Replication.
AB - A wide variety of endogenous and exogenous alkylating agents attack DNA to
preferentially generate N7-alkylguanine (N7-alkylG) adducts. Studies of the
effect of N7-alkylG lesions on biological processes have been difficult in part
because of complications arising from the chemical lability of the positively
charged N7-alkylG, which can readily produce secondary lesions. To assess the
effect of bulky N7-alkylG on DNA replication, we prepared chemically stable N7
benzylguanine (N7bnG)-containing DNA and evaluated nucleotide incorporation
opposite the lesion by human DNA polymerase beta (polbeta), a model enzyme for
high-fidelity DNA polymerases. Kinetic studies showed that the N7-benzyl-G lesion
greatly inhibited dCTP incorporation by polbeta. The crystal structure of polbeta
incorporating dCTP opposite N7bnG showed a Watson-Crick N7bnG:dCTP structure. The
polbeta-N7bnG:dCTP structure showed an open protein conformation, a relatively
disordered dCTP, and a lack of catalytic metal, which explained the inefficient
nucleotide incorporation opposite N7bnG. This indicates that polbeta is sensitive
to major groove adducts in the templating base side and deters nucleotide
incorporation opposite bulky N7-alkylG adducts by adopting a catalytically
incompetent conformation. Substituting Mg2+ for Mn2+ induced an open-to-closed
conformational change due to the presence of catalytic metal and stably bound
dCTP and increased the catalytic efficiency by ~10-fold, highlighting the effect
of binding of the incoming nucleotide and catalytic metal on protein conformation
and nucleotidyl transfer reaction. Overall, these results suggest that, although
bulky alkyl groups at guanine-N7 may not alter base pairing properties of
guanine, the major groove-positioned lesions in the template could impede
nucleotidyl transfer by some DNA polymerases.
PMID- 29957996
TI - Real-Time Nowcasting of Microbiological Water Quality at Recreational Beaches: A
Wavelet and Artificial Neural Network-Based Hybrid Modeling Approach.
AB - The number of beach closings caused by bacterial contamination has continued to
rise in recent years, putting beachgoers at risk of exposure to contaminated
water. Current approaches predict levels of indicator bacteria using regression
models containing a number of explanatory variables. Data-based modeling
approaches can supplement routine monitoring data and provide highly accurate
short-term forecasts of beach water quality. In this paper, we apply the
nonlinear autoregressive network with exogenous inputs (NARX) method with
explanatory variables to predict Escherichia coli concentrations at four Lake
Michigan beach sites. We also apply the nonlinear input-output network (NIO) and
nonlinear autoregressive neural network (NAR) methods in addition to a hybrid
wavelet-NAR (WA-NAR) model and demonstrate their application. All models were
tested using 3 months of observed data. Results revealed that the NARX models
provided the best performance and that the WA-NAR model, which requires no
explanatory variables, outperformed the NIO and NAR models; therefore, the WA-NAR
model is suitable for application to data scarce regions. The models proposed in
this paper were evaluated using multiple performance metrics, including
sensitivity and specificity measures, and produced results comparable or superior
to those of previous mechanistic and statistical models developed for the same
beach sites. The relatively high R2 values between data and the NARX models ( R2
values of ~0.8 for the beach sites and ~0.9 for the river site) indicate that the
new class of models shows promise for beach management.
PMID- 29957997
TI - Anomalous Nonlinear Shot Noise at High Voltage Bias.
AB - Since the work of Walter Schottky, it is known that the shot-noise power for a
completely uncorrelated set of electrons increases linearly with the time
averaged current. At zero temperature and in the absence of inelastic scattering,
the linearity relation between noise power and average current is quite robust,
in many cases even for correlated electrons. Through high-bias shot-noise
measurements on single Au atom point contacts, we find that the noise power in
the high-bias regime shows highly nonlinear behavior even leading to a decrease
in shot noise with voltage. We explain this nonlinearity using a model based on
quantum interference of electron waves with varying path difference due to
scattering from randomly distributed defect sites in the leads, which makes the
transmission probability for these electrons both energy and voltage dependent.
PMID- 29957999
TI - Consider Using Attributable Fraction of Mortality from Acute Respiratory Distress
Syndrome to Guide Sample Size Estimates.
PMID- 29957998
TI - Intramolecular Hydrogen Bonding Enhances Stability and Reactivity of Mononuclear
Cupric Superoxide Complexes.
AB - [(L)CuII(O2*-)]+ (i.e., cupric-superoxo) complexes, as the first and/or key
reactive intermediates in (bio)chemical Cu-oxidative processes, including in the
monooxygenases PHM and DbetaM, have been systematically stabilized by
intramolecular hydrogen bonding within a TMPA ligand-based framework. Also,
gradual strengthening of ligand-derived H-bonding dramatically enhances the
[(L)CuII(O2*-)]+ reactivity toward hydrogen-atom abstraction (HAA) of phenolic O
H bonds. Spectroscopic properties of the superoxo complexes and their azido
analogues, [(L)CuII(N3-)]+, also systematically change as a function of ligand H
bonding capability.
PMID- 29958000
TI - Reply to Tremlett and Kanthimathinathan and to Koopman and Kneyber.
PMID- 29958001
TI - Measurement of Specific Heat and Crystallization in VS55, DP6, and M22
Cryoprotectant Systems With and Without Sucrose.
AB - Cryopreservation represents one if not the only long-term option for tissue and
perhaps future organ banking. In one particular approach, cryopreservation is
achieved by completely avoiding ice formation (or crystallization) through a
process called vitrification. This "ice-free" approach to tissue banking requires
a combination of high-concentration cryoprotective additives such as M22 (9.4 M),
VS55 (8.4 M), or DP6 (6 M) and sufficiently fast rates of cooling and warming to
avoid crystallization. In this article, we report the temperature-dependent
specific heat capacity of the above-mentioned cryoprotective additives in small
volumes (10 mg sample pans) at rates of 5 degrees C/min and 10 degrees C/min
using a commercially available differential scanning calorimetry (TA Instruments
Q1000), in the temperature range of -150 degrees C to 30 degrees C. This data can
be utilized in heat-transfer models to predict thermal histories in a
cryopreservation protocol. More specifically, the effects of temperature
dependence of specific heat due to the presence of three different phases
(liquid, ice, and vitreous phase) can dramatically impact the thermal history and
therefore the outcome of the cryopreservation procedure. The crystallization
potential of these cryoprotectants was also investigated by studying cases of
maximal and minimal crystallization in VS55 and DP6, where M22 did not
crystallize under any rates tested. To further reduce crystallization in VS55 and
DP6, a stabilizing sugar (sucrose) was added in varying concentrations (0.15 M
and 0.6 M) and was shown to further reduce crystallization, particularly in VS55,
at modest rates of cooling (1 degrees C/min, 5 degrees C/min, and 10 degrees
C/min).
PMID- 29958002
TI - Correction to: ABM Clinical Protocol #8: Human Milk Storage Information for Home
Use for Full-Term Infants, Revised 2017, by Eglash A, Simon L, and The Academy of
Breastfeeding Medicine Breastfeed Med 2017;12(7):390-395. DOI:
10.1089/dna.2017.29047.aje.
PMID- 29958003
TI - Intergroup Competition in Exergames: Further Tests of the Kohler Effect.
AB - OBJECTIVE: We examined how competing with a software-generated partner (SGP)
against another human/virtual partner team, in an exercise video game (exergame),
affects individual motivation as measured by effort. MATERIALS AND METHODS:
Participants (n = 90; 49 female; Mage = 19.93 +/- 1.48) were randomly assigned to
one of three conditions: individual control (IC); conjunctive partner, no
competition (PNC); or conjunctive partner, with competition (PWC). Participants
performed the first series of exercises alone. After resting, those in the
partnered conditions performed the remaining trials with a same-sex SGP. Those in
the PWC condition were told that they and their virtual partner would be
competing against another human-virtual partner team. RESULTS: A significant
motivation gain was observed in both partnered conditions compared to control (P
< 0.001), but the partnered groups did not differ significantly. However,
participants in the PWC condition enjoyed the task significantly (P < 0.05) more
than those in the PNC and IC conditions and the PWC participants identified more
with the SGP as a teammate than the PNC participants. CONCLUSIONS: Altogether,
intergroup competition with an SGP may be an enjoyable way to enhance motivation
and performance while exercising.
PMID- 29958004
TI - Accuracy of the Haigis and SRK/T Formulas in Eyes Longer than 29.0 mm and the
Influence of Central Corneal Keratometry Reading.
AB - PURPOSE: To examine the potential relationship of central corneal keratometry
reading (K value) to intraocular lens (IOL) power calculation in extremely long
eyes. MATERIALS AND METHODS: Sixty-three consecutive eyes with an axial length
(AL) longer than 29.0 mm were prospectively enrolled at Shanghai General
Hospital. All eyes underwent uneventful cataract surgery. Central corneal
keratometry, anterior chamber depth, and AL were measured, and IOL power was
calculated using the Haigis and SRK/T formulas. The refractive error associated
with both formulas was calculated, and its relationship with associated factors
was also analyzed. RESULTS: Linear regression showed a statistically significant
relationship between prediction error and K value with both Haigis and SRK/T (P <
0.001, R2 = 0.343 and P < 0.001, R2 = 0.225, respectively). In general, a higher
K value was associated with a hyperopic outcome, whereas a lower K value was
associated with a myopic outcome. There was no difference in the median absolute
error (MedAE) when comparing Haigis and SRK/T (P = 0.081). The 63 eyes were
subsequently divided into an L group (K value < 44.02) and an H group (K value >
44.02) according to the K value. The MedAE produced by SRK/T was lower than that
produced by Haigis in group L, while the MedAE produced by SRK/T was similar to
that produced by Haigis in group H (P = 0.020 and P = 0.799, respectively).
CONCLUSIONS: The average keratometry reading significantly correlated with the
prediction error using Haigis and SRK/T. An adjustment of formulas according to
the K value could achieve better outcomes in long eyes.
PMID- 29958005
TI - Resveratrol Reverts Epigenetic and Transcription Changes Caused by Smoke
Inhalation on Bone-Related Genes in Rats.
AB - We investigated the effects of cigarette smoke (CS) and resveratrol intake on the
modulation of bone repair-related genes through epigenetic mechanisms at the
global and gene-specific levels, after 30 days of calvarial defects were created,
in rats. The samples were assigned to three groups as follows: no CS, CS, and
CS/resveratrol. After evaluation of global (5 hmC) changes and epigenetic and
transcription regulation at gene-specific levels, CS group showed increased 5 hmC
and Tets transcripts with demethylation at Rankl and Trap promoters (p <= 0.01),
linked to their increased gene expression (p <= 0.001). These modifications were
reverted in the CS/resveratrol group. Opposite patterns were observed among CS
and CS/resveratrol for epigenetic enzyme transcripts with higher levels of Dnmts
in the CS/resveratrol (p <= 0.01). No CS and CS/resveratrol demonstrated similar
gene expression levels for all Tets and bone-related genes. Resveratrol reverts
epigenetic and transcription changes caused by CS at both global and gene
specific levels in bone-related and epigenetic machinery genes, emphasizing the
resveratrol as biological modulator for CS in rats.
PMID- 29958006
TI - Can scuba diving offer therapeutic benefit to military veterans experiencing
physical and psychological injuries as a result of combat? A service evaluation
of Deptherapy UK.
AB - PURPOSE: To explore the effectiveness of scuba diving in providing therapeutic
and rehabilitative benefit to ex-service personnel who have experienced traumatic
physical and/or psychological injuries resulting from combat. METHODS: This study
took the form of a service evaluation of Deptherapy, a UK-based niche charity
offering support to military veterans who have experienced life-changing
injuries. Deptherapy provides scuba diving qualifications, consisting of theory
and practical diving experience, to participants alongside a Peer Support Buddy
scheme that provides continuing support to servicemen involved with the charity.
A total of 15 male veterans were invited to take part in the study. The
methodology comprised retrospective and current quantitative measures of mental
well-being and functional ability, utilising the General Health Questionnaire-28,
and subsequent semi-structured interviews with participants, their families and
health professionals. RESULTS: Participants reported an improvement in levels of
anxiety, depression and social functioning, and a reduction in insomnia,
following their involvement in organised scuba diving activities. There was a
mean average difference of 14.3 points improvement on the General Health
Questionnaire-28 scale variants between prior interaction with Deptherapy and
current perceptions following engagement with the programme. The positive
perceptions, as indicated from the semi-structured interviews, were more
pronounced in those whose injuries were predominantly psychological, rather than
physical. CONCLUSION: Scuba diving can offer significant therapeutic benefits,
particularly for ex-military amputees experiencing co-morbid anxiety and/or
chronic psychological adjustment disorders, notably in terms of improvements in
social dysfunction and symptomology of depression. Implications for
Rehabilitation Scuba Diving as a Therapy Military combat can result in
devastating, chronic physical and/or psychological injury. Current research
suggests that a combination of medical and psychological therapy may prove to be
the most beneficial for military veterans. Scuba diving has the potential to
benefit injured veterans due the requirement of complete focus and the feeling of
weightlessness when underwater. This article evaluates whether scuba diving is an
effective physical and psychological therapy through GHQ-28 analysis and veteran
interviews. Scuba diving benefited injured veterans in terms of chronic pain
relief and depression symptoms alleviation.
PMID- 29958007
TI - Understanding the impact of commonly utilized, non-insulin, glucose-lowering
drugs on body weight in patients with type 2 diabetes.
AB - INTRODUCTION: The majority of patients with type 2 diabetes also have obesity.
Obesity increases the risk of developing diabetes and is associated with worsened
glycemic control and increased morbidity and mortality in individuals with
diabetes. Sustained weight loss is associated with improved glycemic control,
potential for diabetes remission, and decreased medical expenditures. Areas
covered: Herein, the impact of commonly utilized, non-insulin, glucose-lowering
drugs on body weight in patients with type 2 diabetes is discussed. The weight
change magnitudes, mechanisms, and any within-class differences are also
explored. Expert opinion: The weight impact of diabetes medications should be
considered when designing treatment regimens, especially in patients who are
overweight or have obesity. Lifestyle modification is paramount for optimal
diabetes management. Therapeutic regimens should ideally be designed to maximize
weight loss and at least minimize or avoid weight gain. Future glucose-lowering
medications should continue to offer improvement in cardiovascular risk factors,
including weight, in order to be accepted into the armamentarium of diabetes
therapy. Therapeutic regimens should be designed to help patients with diabetes
and obesity achieve both glycemic and weight goals. Management of these disease
states is expected to become increasingly integrated.
PMID- 29958008
TI - The EQ-5D-5L Valuation study in Thailand.
AB - BACKGROUND: At present, health technology assessment (HTA) guidelines of many
countries including Thailand have recommended EQ-5D as the preferred method for
assessing utility. This study aims to generate an EQ-5D-5L value set based on
societal preferences of Thai population. METHODS: A 1,207 representative sample
was recruited using a stratified multi-stage quota sampling technique. Face-to
face, computer-assisted interviews using the EuroQol Valuation Technology (EQ-VT)
software were employed. To elicit preference score, each respondent was asked to
value health states using composite time trade-off (cTTO), and discrete choice
experiment (DCE). All data were integrated and analyzed using a hybrid regression
model to estimate the value set. RESULTS: Characteristics of 1,207 participants
were generally similar to those of Thai general population. The coefficients
generated from a hybrid model were logically consistent. The second best value is
0.9436 for health state 11121 and the worst state (55555) value is -0.4212.
Mobility shows the greatest impact to utility decrement. CONCLUSIONS: Our study
developed a Thai value set for EQ-5D using hybrid model. The findings from this
study are of important to facilitate health technology assessment studies to
inform policy decision-making as well as to promote the use of EQ-5D-5L in
various health research in Thailand.
PMID- 29958009
TI - Outbreak of Vibrio parahaemolyticus Associated with Consumption of Raw Oysters in
Canada, 2015.
AB - There has been a steady increase in illness incidence of Vibrio parahaemolyticus
(Vp). The majority of illnesses are associated with consumption of raw oysters.
In the summer of 2015, Canada experienced the largest outbreak associated with
the consumption of raw oysters harvested from British Columbia (BC) coastal
waters. Case investigation of laboratory-confirmed cases was conducted to collect
information on exposures and to assist traceback. Investigations at processors
and oyster sampling were conducted. Eighty-two laboratory-confirmed cases of Vp
infection were reported between January 1 and October 26, 2015. The majority of
the cases were reported in BC, associated with consumption of raw BC oysters in
restaurants. Sea surface temperatures were above the historical levels in 2015.
This outbreak identified the need to improve surveillance and response to
increases in human cases of Vp. This is of particular importance due to the
potential for increasing water temperatures and the likelihood of additional
outbreaks of Vibrio.
PMID- 29958010
TI - Development of a toileting performance assessment test for patients in the early
stroke phase.
AB - PURPOSE: The study aimed to develop a toileting performance assessment test to
measure the toileting performance ability of patients in the early phase after
stroke. METHODS: In this study, 214 stroke patients were enrolled. Cronbach's
alpha, Spearman's rank correlations (rho values) with the toileting-related items
of the functional independence measure and Barthel Index, interrater reliability
(weighted kappa), and responsiveness (standardized response mean) were evaluated.
Receiver operating characteristic and the area under the curves were utilized to
determine the cutoff scores for the significance of the independence of toilet
ability with the functional independence measure and Barthel Index. RESULTS:
Cronbach's alpha was >=0.90. The p values between toileting performance
assessment test and Barthel Index and between toileting performance assessment
test and functional independence measure were 0.88 and 0.86, respectively. The
weighted kappa for each item was >=0.61. The standardized response means were
0.81 for the functional independence measure, 0.70 for the Barthel Index, and
0.93 for the toileting performance assessment test. Cutoff scores of the
toileting performance assessment test were 18 points. CONCLUSIONS: The toileting
performance assessment test has acceptable psychometric properties and proved
useful in assessing toileting performance ability of patients in the early phase
after stroke. Implications for rehabilitation Toileting performance assessment
test demonstrated acceptable psychometric properties, and it can be useful for
assessing the toileting ability of patients in the early phase after stroke.
Toileting performance assessment test should provide information that leads to
lowered risk of falls while toileting, and the information gathered can assist
patients in achieving early toileting independence after stroke. As the
development of toileting performance assessment test excluded patients with
cognitive disabilities, the item for cognitive function should be developed as
well.
PMID- 29958011
TI - Efficacy and safety of the combination fluticasone propionate plus salmeterol in
asthmatic preschoolers: An observational study.
AB - BACKGROUND: Inhaled Corticosteroids (ICS) are the cornerstone of asthma
management in pediatric patients. However, in some cases, asthma is not
adequately controlled on ICS alone. Long-acting beta2-agonists (LABA) are one of
the available additional therapies but their use has rarely been studied among
children younger than 5 years. OBJECTIVE: The aim of this observational study was
to evaluate the efficacy and safety of the combination of fluticasone propionate
and salmeterol (FP/SA) in asthmatic children younger than 5 years of age.
METHODS: A retrospective study of 796 children under the age of 5 years (2.87 +/-
1.22 years, 64.2% males), who were treated with FP/SA was conducted.
Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal
wheeze and drug-related side-effects were recorded through children's medical
records. RESULTS: The children had previously received short-acting beta2
agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean
duration of therapy with FP/SA was 12.45 +/- 9.14 months. After adjusting for
age, gender, and duration of treatment, a 89% reduction was recorded in annual
hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy,
p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs.
after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after:
6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous
treatment carry-on effect was observed. No major drug-related side-effects
occurred in the study group. CONCLUSIONS: Combination therapy (FP/SA) is well
tolerated and highly effective in asthmatic children under the age of 5 years.
PMID- 29958012
TI - CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria alternata.
AB - The airway epithelial cell (AEC) response to allergens helps initiate and
propagate allergic inflammation in asthma. CARMA3 is a scaffold protein that
mediates G protein-coupled receptor-induced NF-kappaB activation in airway
epithelium. In this study, we demonstrate that mice with CARMA3-deficient AECs
have reduced airway inflammation, as well as reduced type 2 cytokine levels in
response to Alternaria alternata. These mice also have reduced production of IL
33 and IL-25, and reduced numbers of innate lymphoid cells in the lung. We also
show that CARMA3-deficient human AECs have decreased production of proasthmatic
mediators in response to A. alternata. Finally, we show that CARMA3 interacts
with inositol 1,4,5-trisphosphate receptors in AECs, and that inhibition of
CARMA3 signaling reduces A. alternata-induced intracellular calcium release. In
conclusion, we show that CARMA3 signaling in AECs helps mediate A. alternata
induced allergic airway inflammation, and that CARMA3 is an important signaling
molecule for type 2 immune responses in the lung.
PMID- 29958013
TI - Clicking Health Risk Messages on Social Media: Moderated Mediation Paths Through
Perceived Threat, Perceived Efficacy, and Fear Arousal.
AB - This study drew on appraisal theory to examine how fear appeal messages and
individual coping styles combined to drive users' intention to click (ITC) health
risk messages on social media. A 2 * 2 * 2 mixed-design experiment was conducted,
with threat and efficacy as between subject factors and message as the within
subject factor. The results suggested that: (1) threat and efficacy message
influenced ITC via the mediating effect of perceived threat, and perceived
efficacy; (2) fear arousal was positively related to intention to click; (3)
blunting style used by the participant suppressed fear arousal's ability to
mobilize ITC; and (4) monitoring style had a positive main effect on ITC.
Theoretical and practical implications are discussed.
PMID- 29958014
TI - A concerns report survey of physical activity support needs of people with
moderate-to-severe MS disability and family caregivers.
AB - PURPOSE: To identify the most pressing needs for community resources to support
physical activity participation, determinants of perceived need, and barriers to
co-participation in physical activity among people with multiple sclerosis (MS)
who have moderate-to-severe disability and the family caregivers providing
assistance to such individuals. METHODS: Seventy-eight people with MS and 46
family caregivers participated in this cross-sectional survey study, guided by
the Concerns Report Methodology. RESULTS: The results show differences between
groups in rankings for some need items. However, three need items were
prioritized by both people with MS and the family caregivers: (1) information
about available resources to support physical activity participation, with Need
Indexes of 76.6% and 52.3%, respectively; (2) programs that support joint
participation of people with MS together with their caregivers in physical
activity, with Need Indexes of 62.0% and 68.9%, respectively; and (3) programs
that have affordable total cost of participation, with Need Indexes of 50.7% and
52.3%, respectively. A broad range of factors (i.e., education, living situation,
type of community, marital status, employment, and income, as well as comorbidity
status) was significantly associated with one or more of these need items.
Several modifiable impairment-related, personal and logistical factors were
identified by both groups as barriers to co-participation in physical activity.
CONCLUSIONS: The findings highlight the complexity of developing community
resources that target physical activity promotion in MS dyads. Importantly, our
findings suggest that resources designed to influence dyadic physical activity
participation need to include content that are responsive and tailored to both
the needs of the person with MS and the unique needs of the family caregiver. The
results also underscore the importance of reinforcing physical activity as a
shared behavior and providing information about affordable options for exercising
together to the benefit of each individual and the dyad (i.e., partnership).
Overall, our findings provide a possible starting point to guide the
identification of potential participants that might benefit the most from future
intervention development work. Implications for rehabilitation MS has life
altering consequences for people with the disease and the family caregivers who
support such individuals. Rehabilitation professionals need to reinforce physical
activity as a shared behavior and provide information about affordable options
for exercising together to the benefit of each individual and the dyad. A "one
size-fits-all" approach is not appropriate, therefore, clinicians need to
identify flexible and pragmatic strategies to increase dyadic participation in
the presence of unique caregiver and care-recipients barriers that might impede
such an increase.
PMID- 29958016
TI - Barriers and solutions to participation in exercise for moderately disabled
people with multiple sclerosis not currently exercising: a consensus development
study using nominal group technique.
AB - BACKGROUND: Multiple sclerosis (MS) is a chronic, progressive neurological
condition. The aim of this study was to explore consensus on the barriers and
solutions to exercise for people with MS living in Scotland. METHOD: Thirty-five
people with MS, not regularly exercising, were recruited and took part in five
Nominal Group Technique groups throughout Scotland. Background information was
collected on participants prior to each group. Participants individually and
silently listed their barriers and solutions to participating in exercise. Group
discussion then clarified, amended and merged ideas. Participants then ranked
ideas by choosing five barriers and solutions to exercise participation. Data
were analyzed using descriptive statistics and by carrying out a thematic
grouping. RESULTS: Consensus was that fatigue was a barrier to exercise
participation . Other identified barriers were a lack of support and advice, the
impairments arising from the condition and time. No single item achieved
consensus for solutions but exercising with others, receiving support, having a
positive attitude, finding time and minimizing environmental barriers were all
suggested as solutions to assist in exercise participation. CONCLUSIONS: People
with MS should be provided with information on how to manage their fatigue
alongside any exercise prescription. Information and support should be given on
how to personalize exercise to suit individual needs and abilities to overcome
some of the barriers suggested within this study. Implications for rehabilitation
More exercise opportunities are required. Exercise should be personalized to
address the individual needs of the person with MS. Any identified barriers to
exercise should be addressed.
PMID- 29958017
TI - Maintenance of multidomain neurocognitive functions in pediatric patients after
proton beam therapy: A prospective case-series study.
AB - Proton Beam Therapy (PBT) was developed to minimize the harmful results of
radiation therapy as treatment for brain tumors. This study examined the
neurocognitive outcomes of PBT in pediatric patients. A total of 8 patients, who
received either PBT or photon radiotherapy (XRT), were evaluated with multiple
cognitive functions, which include intelligence, memory, executive functions, and
attention. Most of patients performed average-to-superior levels of
neurocognitive functions (NCF), except that a deterioration of executive
functions was revealed in two patients receiving XRT. This study might be the
first one to show the maintenance of multidomain NCF after PBT.
PMID- 29958015
TI - Inhaled TRIM72 Protein Protects Ventilation Injury to the Lung through Injury
guided Cell Repair.
AB - Studies showed that TRIM72 is essential for repair of alveolar cell membrane
disruptions, and exogenous recombinant human TRIM72 protein (rhT72) demonstrated
tissue-mending properties in animal models of tissue injury. Here we examine the
mechanisms of rhT72-mediated lung cell protection in vitro and test the efficacy
of inhaled rhT72 in reducing tissue pathology in a mouse model of ventilator
induced lung injury. In vitro lung cell injury was induced by glass beads and
stretching. Ventilator-induced lung injury was modeled by injurious ventilation
at 30 ml/kg tidal volume. Affinity-purified rhT72 or control proteins were added
into culture medium or applied through nebulization. Cellular uptake and in vivo
distribution of rhT72 were detected by imaging and immunostaining. Exogenous
rhT72 maintains membrane integrity of alveolar epithelial cells subjected to
glass bead injury in a dose-dependent manner. Inhaled rhT72 decreases the number
of fatally injured alveolar cells, and ameliorates tissue-damaging indicators and
cell injury markers after injurious ventilation. Using in vitro stretching
assays, we reveal that rhT72 improves both cellular resilience to membrane
wounding and membrane repair after injury. Image analysis detected rhT72 uptake
by rat alveolar epithelial cells, which can be inhibited by a cholesterol
disrupting agent. In addition, inhaled rhT72 distributes to the distal lungs,
where it colocalizes with phosphatidylserine detection on nonpermeabilized lung
slices to label wounded cells. In conclusion, our study showed that inhaled rhT72
accumulates in injured lungs and protects lung tissue from ventilator injury, the
mechanisms of which include improving cell resilience to membrane wounding,
localizing to injured membrane, and augmenting membrane repair.
PMID- 29958018
TI - Association Between TGF-beta1 Polymorphisms and Asthma Susceptibility Among the
Chinese: A Meta-Analysis.
AB - OBJECTIVE: Asthma is the most common chronic pulmonary disease in China and is
characterized by airway inflammation and episodic airflow obstruction. The aim of
this meta-analysis was to evaluate the relation of two transforming growth factor
beta1 (TGF-beta1) polymorphisms with asthma risk in Chinese population. METHODS:
PubMed, Springer, EMBASE, MEDLINE, CNKI (China National Knowledge
Infrastructure), and Wanfang databases were used to search and retrieve relevant
eligible case-control studies published through December 2017. The odds ratios
(OR) and 95% confidence intervals (CI) were used to evaluate the effect. RESULTS:
A total of 2040 asthma patients and 1952 controls from 12 studies were analyzed.
Two polymorphic sites of TGF-beta1 gene were identified: -509C/T and +869T/C. We
found that the -509C/T polymorphism was associated with increased asthma risk
under the heterozygous model (CT vs. CC: OR = 1.40, 95% CI = 1.03-1.90, p = 0.03)
and the dominant model (TT+CT vs. CC: OR = 1.41, 95% CI = 1.05-1.90, p = 0.02).
Subgroup analyses by age suggested that -509C/T variant was associated with
childhood asthma. Analysis of disease severity indicated that this variant was
associated with both mild-to-moderate asthma and severe asthma. However, the
+869T/C polymorphism was not associated with asthma susceptibility in subgroup
analysis by age or disease severity. CONCLUSIONS: This study demonstrated that
the -509C/T polymorphism of the TGF-beta1 gene might be a risk factor for asthma
in the Chinese population, especially in Chinese children. Further large-scale
case-control studies are still required.
PMID- 29958019
TI - The use of bronchoscopy in critically ill patients: considerations and
complications.
AB - INTRODUCTION: Flexible bronchoscopy has been well established for diagnostic and
therapeutic purposes in critically ill patients. Areas covered: This review
outlines the clinical evidence of the utility and safety of flexible bronchoscopy
in the intensive care unit, as well as specific considerations, including
practical points and potential complications, in critically ill patients. Expert
commentary: Its ease to learn and perform and its capacity for bedside
application with relatively few complications make flexible bronchoscopy an
indispensable tool in the intensive care unit setting. The main indications for
flexible bronchoscopy in the intensive care unit are the visualization of the
airways, sampling for diagnostic purposes and management of the artificial
airways. The decision to perform flexible bronchoscopy can only be made by trade
offs between potential risks and benefits because of the fragile nature of the
critically ill. Flexible bronchoscopy-associated serious adverse events are
inevitable in cases of a lack of expertise or appropriate precautions.
PMID- 29958020
TI - Effects of Cyberbullying and Cybervictimization on Early Adolescents' Mental
Health: Differential Mediating Roles of Perceived Peer Relationship Stress.
AB - The purpose of this study was to examine the differential mediational roles of
perceived peer relationship stress (PPRS) in accounting for the association
between cyberbullying (CB) and cybervictimization (CV) and mental health among
early adolescents in cross-sectional data and longitudinal data, respectively. A
total of 606 early adolescents completed questionnaires as part of a 3-year
longitudinal study on three occasions at 1-year intervals. Structural equation
modeling revealed that (1) compared to CB, CV showed a stronger relationship with
mental health. (2) In contrast to its role in CV, PPRS did not mediate the link
between mental health and CB in both cross-sectional and longitudinal models.
PPRS mediated the relationship between CV and mental health in both cross
sectional and longitudinal models. Limitations and practical applications of the
study were discussed.
PMID- 29958021
TI - Germ line predisposition to myeloid malignancies appearing in adulthood.
AB - INTRODUCTION: Germ line predisposition to myeloid neoplasms has been incorporated
in the WHO 2016 classification of myeloid neoplasms and acute leukemia. The new
category of disease is named hereditary myeloid disorder (HMD). Although most
myeloid neoplasms are sporadic, germ line mutations and familial predisposition
can contribute to development of chronic myeloid diseases and acute myeloid
leukemia. This finding and upcoming frequent use of genome wide detection of
molecular aberrations will lead to a higher detection rate of a genetic
predisposition and influence treatment decisions. Hereditary predisposition is
responsible for 5-10% of myeloid malignancies. Management of affected patients
begins by the awareness of treating physicians of the problem and a precise work
up of the patient and family members. Areas covered: This review focuses on
current knowledge about germ line predisposition for myeloid neoplasms including
diagnostic, prognostic, and therapeutic aspects in adult patients. Essential
information for clinical routine is provided. Expert commentary: Compared to a
patient without predisposition, adaptation of treatment strategy for patients
with an HMD is often necessary, especially to avoid higher risk of relapse or
higher toxicity during chemotherapy or transplantation. Mistakes in choice of a
related donor can be omitted. Relatives at risk of developing a HMD need specific
surveillance.
PMID- 29958024
TI - Real-Time Continuous Glucose Monitoring Usage in Pilots with Diabetes: An Option
to Improve Safety.
PMID- 29958022
TI - Adaptability of Closed Loop During Labor, Delivery, and Postpartum: A Secondary
Analysis of Data from Two Randomized Crossover Trials in Type 1 Diabetes
Pregnancy.
AB - Tight glucose control during labor and delivery is recommended for pregnant women
with type 1 diabetes. This can be challenging to achieve using the current
treatment modalities. The automated nature of closed loop and its ability to
adapt to real-time glucose levels make it well suited for use during labor,
delivery, and the immediate postpartum period. We report observational data of
participants from two randomized crossover trials who chose to continue using
closed loop during labor, delivery, and postpartum. Labor was defined as the 24 h
before delivery and postpartum as the 48 h after delivery. The glucose target
range during pregnancy was 3.5-7.8 mmol/L (63-140 mg/dL) and 3.9-10 mmol/L (70
180 mg/dL) after delivery. Twenty-seven (84.4%) of the potential 32 trial
participants used closed loop through labor, delivery, and postpartum. Use of
closed loop was associated with 82.0% (interquartile range [IQR] 49.3, 93.0) time
in-target range during labor and delivery and a mean glucose of 6.9 +/- 1.4
mmol/L (124 +/- 25 mg/dL). Closed loop performed well throughout vaginal,
elective, and emergency cesarean section deliveries. Postpartum, women spent
83.3% (IQR 75.2, 94.6) time-in-target range (3.9-10.0 mmol/L [70-180 mg/dL]),
with a mean glucose of 7.2 +/- 1.4 mmol/L (130 +/- 25 mg/dL). There was no
difference in maternal glucose concentration between mothers of infants with and
without neonatal hypoglycemia (6.9 +/- 1.6 mmol/L and 6.8 +/- 1.1 mmol/L [124 +/-
29 mg/dL and 122 +/- 20 mg/dL] respectively; P = 0.84). Automated closed-loop
insulin delivery is feasible during hospital admissions for labor, delivery, and
postpartum. Larger scale studies are needed to evaluate its efficacy compared
with current clinical approaches as well as understand how women and healthcare
providers will adopt this technology.
PMID- 29958023
TI - Evaluation of an Artificial Pancreas with Enhanced Model Predictive Control and a
Glucose Prediction Trust Index with Unannounced Exercise.
AB - BACKGROUND: We investigated the safety and efficacy of the addition of a trust
index to enhanced Model Predictive Control (eMPC) Artificial Pancreas (AP) that
works by adjusting the responsiveness of the controller's insulin delivery based
on the confidence intervals around predictions of glucose trends. This
constitutes a dynamic adaptation of the controller's parameters in contrast with
the widespread AP implementation of individualized fixed controller tuning.
MATERIALS AND METHODS: After 1 week of sensor-augmented pump (SAP) use, subjects
completed a 48-h AP admission that included three meals/day (carbohydrate range
29-57 g/meal), a 1-h unannounced brisk walk, and two overnight periods. Endpoints
included sensor glucose percentage time 70-180, <70, >180 mg/dL, number of
hypoglycemic events, and assessment of the trust index versus standard eMPC
glucose predictions. RESULTS: Baseline characteristics for the 15 subjects who
completed the study (mean +/- SD) were age 46.1 +/- 17.8 years, HbA1c 7.2% +/-
1.0%, diabetes duration 26.8 +/- 17.6 years, and total daily dose (TDD) 35.5 +/-
16.4 U/day. Mean sensor glucose percent time 70-180 mg/dL (88.0% +/- 8.0% vs.
74.6% +/- 9.4%), <70 mg/dL (1.5% +/- 1.9% vs. 7.8% +/- 6.0%), and number of
hypoglycemic events (0.6 +/- 0.6 vs. 6.3 +/- 3.4), all showed statistically
significant improvement during AP use compared with the SAP run-in (P < 0.001).
On average, the trust index enhanced controller responsiveness to predicted hyper
and hypoglycemia by 26% (P < 0.005). CONCLUSIONS: In this population of well
controlled patients, we conclude that eMPC with trust index AP achieved nearly
90% time in the target glucose range. Additional studies will further validate
these results.
PMID- 29958025
TI - Duration of Catheter Use in Patients with Diabetes Using Continuous Subcutaneous
Insulin Infusion: A Review.
AB - Increasing proportions of patients with diabetes use continuous subcutaneous
insulin infusion (CSII) therapy mostly due to its clinical efficacy and
flexibility for insulin dosing and adjustments. Some challenges are nevertheless
associated with this technology. A key and underlooked component of CSII
technical difficulties is the subcutaneous catheter used to infuse insulin.
Several adverse events (AEs) have been experienced by patients in relation to
catheters, such as blockage, kinking, and insertion site reactions, including
irritation, infections, lipohypertrophies etc., all of which could compromise the
metabolic control. With the objective of minimizing these AEs, recommendations
for changing catheters every 2-3 days have historically been provided by
manufacturers based on reports derived from small studies and anecdotal data. The
aim of this review was to provide an updated analysis of current recommendations
and patients' practices in relation to frequency of catheter change. Our main
findings are: (1) adequately designed and powered studies investigating optimal
catheter wearing time are still lacking; (2) increasing catheter wearing time is
generally associated with increased frequency of catheter AEs; (3) however,
interpatient variability is large, with some individuals needing to change their
catheters every 2-3 days, whereas others probably being able to keep them in
place for longer periods without problems. Further research is thus warranted to
provide more solid and evidence-based recommendations while exploring
personalized approaches at the same time. Increasing catheter wear life without
significant side effects is an important goal to simplify CSII therapy and reduce
its associated costs and burdens.
PMID- 29958026
TI - Setting Positive End-Expiratory Pressure in Pediatric Acute Respiratory Distress
Syndrome: Cookbook or Individualized Titration?
PMID- 29958027
TI - Effect of Antioxidant Supplementation on Total Antioxidant Status in Indian
Children with Type 1 Diabetes.
AB - Hyperglycemia results in the overproduction of free oxygen radicals that impair
the endogenous antioxidant defenses. A randomized controlled trial was conducted
to compare the effect of 3 months of antioxidant supplementation in the form of
foods rich in micronutrients with pharmacological supplement on total antioxidant
status of Indian children with type 1 diabetes. Ninety children with diabetes
(mean age 11.5 +/- 3.6 yrs, 37 boys) were randomly allocated to three groups:
Group 1 (n = 31) = DM controls; Group 2 (n = 30) = multimicronutrient syrup; and
Group 3 (n = 29) = dietary supplements (nine snack recipes rich in
micronutrients). They received intervention for 3 months. Healthy controls were
enrolled from local schools. Fasting blood was tested for total antioxidant
status (TAS) and glycosylated hemoglobin (HbA1C). Children with diabetes had
lower TAS (0.70 +/- 0.2 vs. 1 +/- 0.24 mmol/l, p = .0001) compared to healthy
controls. Anthropometric and biochemical parameters were similar at baseline for
all groups of diabetic children. Group 1 showed significant deterioration in TAS
at endline (0.72 +/- 0.16 vs. 0.60 +/- 0.17 mmol/l, p = .008). Increase in TAS
recorded in Group 2 was from 0.66 +/- 0.21 to 0.70 +/- 0.16 mmol/l and in Group 3
was from 0.68 to 0.73 mmol/l. There was a significant difference between Group 1
and Group 3 for percentage change in TAS (-13% vs. 16%, p = .035).
Postsupplementation there was an increase in TAS values in children with
diabetes, but they were still lower than in healthy controls. Indian diabetic
children have compromised antioxidant status, which may be improved by
incorporation of multimicronutrient-rich recipes in their diets.
PMID- 29958028
TI - Implicated Food Products for Listeriosis and Changes in Serovars of Listeria
monocytogenes Affecting Humans in Recent Decades.
AB - Listeriosis is a foodborne disease with a high fatality rate, and infection is
mostly transmitted through ready-to-eat (RTE) foods contaminated with Listeria
monocytogenes, such as gravad/smoked fish, soft cheeses, and sliced processed
delicatessen (deli) meat. Food products/dishes stored in vacuum or in modified
atmospheres and with extended refrigerator shelf lives provide an opportunity for
L. monocytogenes to multiply to large numbers toward the end of the shelf life.
Elderly, pregnant women, neonates, and immunocompromised individuals are
particularly susceptible to L. monocytogenes. Listeriosis in humans manifests
primarily as septicemia, meningitis, encephalitis, gastrointestinal infection,
and abortion. In the mid 1990s and early 2000s a shift from L. monocytogenes
serovar 4b to serovar 1/2a causing human listeriosis occurred, and serovar 1/2a
is becoming more frequently linked to outbreaks of listeriosis, particularly in
Europe and Northern America. Consumer lifestyle has changed, and less time is
available for food preparation. Modern lifestyle has markedly changed eating
habits worldwide, with a consequent increased demand for RTE foods; therefore,
more RTE and take away foods are consumed. There is a concern that many Listeria
outbreaks are reported from hospitals. Therefore, it is vitally important that
foods (especially cooked and chilled) delivered to hospitals and residential
homes for senior citizens and elderly people are reheated to at least 72 degrees
C: cold food, such as turkey deli meat and cold-smoked and gravad salmon should
be free from L. monocytogenes. Several countries have zero tolerance for RTE
foods that support the growth of Listeria.
PMID- 29958029
TI - In Vitro Evaluation of Antioxidant Activity and Antibacterial Effects and
Measurement of Total Phenolic and Flavonoid Contents of Quercus brantii L. Fruit
Extract.
AB - Plant-based extracts, as alternatives to chemical compounds, are commonly use in
pharmaceutical and food industries. Antibacterial properties of extracts are
mainly considered in medicine. Because of the high incidence of infectious
diseases, it is helpful to identify more agents that are able to treat diseases.
Antioxidant effects have been reported for different plant extracts. We aimed to
investigate antioxidant activity, total phenolic and flavonoid contents, and
antibacterial effect of Quercus brantii L. fruit extract. In this study, Q.
brantii L. fruit was extracted by maceration using ethanol 70%. Total phenolic
content was determined by Folin-Ciocalceu reagent and gallic acid equivalence,
and antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH)
compared to butylated hydroxytoluene (BHT). Antibacterial effects were
investigated by broth microdilution and measurement of minimum inhibitory
concentration (MIC) and minimum bactericidal concentration (MBC). Then the
effects of different concentrations of extract on Staphylococcus aureus and
Enterococcus faecalis growth were investigated in comparison with vancomycin and
nitrofurantoin. Our findings demonstrate that antioxidant activity of
hydroalcoholic extract of Q. brantii L. fruit was more than that of BHT. Total
phenolic content was derived (3.010 mg GAE/g DW). Flavonol and flavonoid contents
were 1.813 and 0.654 mg/g, respectively. The extract was found to exert
significant inhibitory effects on both studied bacteria. S. aureus was more
susceptible than E. faecalis to Q. brantii L. fruit extract. Q. brantii L. fruit
extract can exert considerable antioxidant effects, contains high amounts of
phenolic, flavonol, and flavonoid compounds, and inhibits bacterial growth.
PMID- 29958030
TI - Suppression of Th1-Mediated Keratoconjunctivitis Sicca by Lifitegrast.
AB - PURPOSE: Increased interferon gamma (IFN-gamma) expression in dry eye causes
ocular surface epithelial disease termed keratoconjunctivitis sicca (KCS). The
purpose of this study was to investigated the effects of the LFA-1 antagonist,
lifitegrast, in a mouse desiccating stress (DS) dry eye model that develops KCS
similar to Sjogren syndrome. METHODS: Mice were treated with vehicle or
lifitegrast twice daily for 5 days and expression of Th1 family genes (IFN-gamma,
CXCL9, and CXCL11) was evaluated by real-time polymerase chain reaction. Cornea
barrier function was assessed by Oregon Green dextran staining and goblet cell
number and area were measured. RESULTS: Compared to the vehicle-treated group,
the lifitegrast-treated group had significantly lower expression of Th1 family
genes, less corneal barrier disruption, and greater conjunctival goblet cell
density/area. CONCLUSIONS: These findings indicate that lifitegrast inhibits DS
induced IFN-gamma expression and KCS. This suggests that ICAM-LFA-1 signaling is
involved with generation of Th1 inflammation in KCS.
PMID- 29958031
TI - Effect of the Aqueous Extract of Lantana grisebachii Stuck Against Bioaccumulated
Arsenic-Induced Oxidative and Lipid Dysfunction in Rat Splenocytes.
AB - Arsenic (As) is a worldwide immunotoxic agent that is in contaminated waters and
consumed by mammals. Phytotherapy may counteract its harmful effects. Lantana
grisebachii Stuck (LG, Verbenaceae) and its extract are proposed as protective,
given vvits in vitro bioactivity. The aim was to determine the protective
capacity of the aqueous LG extract on splenocytes exposed in vivo to arsenic.
Splenocytes were obtained from an arsenicosis model (Wistar rats consuming orally
0 [control; C] or 5 mg/Kg/d of As) that received 0-100 mg/Kg/d of LG extract for
30 days. As content (total reflection X-ray fluorescence), fatty acid profile
(gas chromatography), gamma-glutamyl transpeptidase activity (Szasz method),
peroxides (xylenol orange-based assay), and nitrites (Griess reaction) were then
assayed in viable splenocytes. Data were analyzed with ANOVA and the Tukey's test
(p < .05). It was observed that the splenocytes contained 2.2 mg/Kg of this
elemental arsenic. With gamma-glutamyl transpeptidase inhibition and consequent
triggering of hydroperoxides (p < .05), it was observed to increase saturated
fatty acids and alter lipid profiles. LG treatment avoided damaging effects with
values similar to unexposed C (p < .05), and cellular arsenic concentration (p <
.0001). In conclusion, the aqueous extract of L. grisebachii counteracted arsenic
toxicity in rat splenocytes by preventing its cellular accumulation and induction
of lipid and redox disturbances, which may impair immune function.
PMID- 29958032
TI - Dietary Supplement and Complementary and Alternative Medicine Use Are Highly
Prevalent in Patients with Gastrointestinal Disorders: Results from an Online
Survey.
AB - The use of complementary and alternative medicine (CAM) is widespread among
adults in the United States to self-treat a range of disorders, including
gastrointestinal (GI) disorders. This study determined the self-reported use of
CAM, including dietary supplements, in managing GI symptoms among Internet users
and investigated perceived effects of supplement use on GI symptoms. We used a
cross-sectional, descriptive, correlational design. A Qualtrics online survey was
utilized to collect data through various websites. Focused areas include
demographics, health evaluation, health issue(s), supplement and CAM use, and GI
symptoms. Of the participants included in the study, a majority (88%) were women
and half (50.1%) were between the ages of 26 and 45. Most participants (84.5%)
reported use of herbal supplements, and 84.8% of the participants used herbal
supplements for a specific health problem. The most common reported health
condition was gastroesophageal reflux (44.4%). The attrition rate was low at 22%.
The novelty of using an anonymous online survey to collect data on supplement use
in GI disorders indicated a high prevalence of dietary and herbal supplement use
among persons with GI disorders comparable to previous reports. Health-care
providers should ask patients about supplement use in addition to prescribed
medications and communicate effectively if conventional pharmacotherapy is not
sufficient to manage symptoms or patients are inclined to use supplements.
PMID- 29958033
TI - Treat the Patient, Not the Test When a Hospitalized Patient in Status Epilepticus
Transitions to Comfort-Focused Goals of Care.
AB - Status epilepticus is a common and under-recognized cause of unconsciousness
among hospitalized patients. It can clinically mimic delirium and other causes of
acute mental status change, especially when clinically relevant seizure activity
is not appreciated on physical examination. While the successful treatment of
status epilepticus may require anesthetic dosing of antiepileptics such as
barbiturates, these seemingly drastic therapeutic measures are justified when
goals of care are life prolonging as they may allow a patient to regain
consciousness and meaningfully interact with loved ones. However, medical burden
from electroencephalogram (EEG) monitoring and other care associated with its
diagnosis and treatment can contribute to distress for patients who may be dying
from a comorbid illness. Furthermore, when goals of care transition to comfort,
care challenges can result regarding the ongoing management of barbiturates or
other sedatives, previously prescribed to treat the status epilepticus. In this
case study, the lack of clinically significant seizure activity led us to
conclude that the discontinuation of a barbiturate infusion and the EEG
monitoring was the clinically appropriate approach for a dying patient with
comfort goals of care and nonconvulsive status epilepticus.
PMID- 29958034
TI - A Purported Detoxification Supplement Does Not Improve Body Composition, Waist
Circumference, Blood Markers, or Gastrointestinal Symptoms in Healthy Adult
Females.
AB - Numerous popular "detoxification" supplements claim to promote the removal of
harmful compounds from the body, thereby alleviating gastrointestinal symptoms,
improving body composition, and enhancing overall health. The present double
blind, randomized, placebo-controlled trial was conducted to examine the effects
of a purported detoxification supplement in healthy young adult females.
Participants were randomly assigned to consume a multi-ingredient supplement or
placebo daily for four weeks. The supplement contained 1,350 mg/serving of a
proprietary blend of papaya leaf, cascara sagrada bark, slippery elm bark,
peppermint leaf, red raspberry leaf, fenugreek seed, ginger root, and senna leaf.
Body composition, waist circumferences, symptoms of gastrointestinal distress,
and blood safety markers were evaluated before and after supplementation. Twenty
two participants completed the study, and data were analyzed via two-way mixed
ANOVA and t tests. No beneficial or harmful effects of supplementation were found
for body composition, waist circumference, gastrointestinal symptoms, or blood
markers. These results indicate that consuming a commercially available dietary
supplement that purportedly provides detoxification and body composition benefits
is apparently safe in healthy young adult females but does not provide any
beneficial effects for body composition or gastrointestinal symptoms.
PMID- 29958035
TI - Teaching professionalism: some features in Canadian physiotherapy programs.
AB - The role of "professionalism" is core to many health professions including
Physical Therapy (PT), and the development of competence in professionalism is a
key requirement of entry-to-practice PT programs. However, the actual curriculum,
teaching methodologies, and evaluation methods currently used to develop
professional competence during PT training programs in Canada are unclear. This
study explored current teaching practices, evaluation and curricular content
related to professionalism in Canadian entry-to-practice PT programs. Results
showed that teaching practices related to professionalism were not necessarily
congruent with methods promulgated by educational theory and relied heavily on
lecture, while more appropriate strategies such as simulation and role play were
under-utilized. The numbers of different teaching methods utilized for specific
aspects of professionalism were variable. Emphasis on different curricular areas
related to professionalism also varied: communication was given the most emphasis
while change management was under-represented. It is posited that teaching
methods related to professionalism could be improved and curricular content and
emphasis should also be reconsidered.
PMID- 29958036
TI - Risk Prediction Model for Cisplatin-Associated Acute Kidney Injury.
PMID- 29958038
TI - Reply to T. Kurokawa et al.
PMID- 29958037
TI - Managing Cancer and Living Meaningfully (CALM): A Randomized Controlled Trial of
a Psychological Intervention for Patients With Advanced Cancer.
AB - Purpose Individuals with advanced cancer experience substantial distress in
response to disease burden and impending mortality. Managing Cancer And Living
Meaningfully (CALM) is a novel, brief, manualized psychotherapeutic intervention
intended to treat and prevent depression and end-of-life distress in patients
with advanced cancer. We conducted a randomized controlled trial to compare CALM
with usual care (UC) in this population. Methods Patients with advanced cancer
were recruited from outpatient oncology clinics at a comprehensive cancer center
into an unblinded randomized controlled trial. Permuted block randomization
stratified by Patient Health Questionnaire-9 depression score allocated
participants to CALM plus UC or to UC alone. Assessments of depressive symptoms
(primary outcome), death-related distress, and other secondary outcomes were
conducted at baseline, 3 months (primary end point), and 6 months (trial end
point). Analyses were by intention to treat. Analysis of covariance was used to
test for outcome differences between groups at follow-up, controlling for
baseline. Mixed-model results are reported. Results Participants (n = 305) were
recruited between February 3, 2012, and March 4, 2016, and randomly assigned to
CALM (n = 151) or UC (n = 154). CALM participants reported less-severe depressive
symptoms than UC participants at 3 months (Delta = 1.09; P = .04; Cohen's d =
0.23; 95% CI, 0.04 to 2.13) and at 6 months (Delta = 1.29; P = .02; d = 0.29; 95%
CI, 0.24 to 2.35). Significant findings for greater end-of-life preparation at 6
months also favored CALM versus UC. No adverse effects were identified.
Conclusion Findings suggest that CALM is an effective intervention that provides
a systematic approach to alleviating depressive symptoms in patients with
advanced cancer and addresses the predictable challenges these patients face.
PMID- 29958039
TI - Gelidiella acerosa Exhibits Neuroprotective Effect Against Amyloid Beta 25-35
Peptide-Induced Toxicity in PC12 Cells.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder with
multiple pathological consequences such as oxidative stress, inflammation,
apoptosis, cholinergic deficit, amyloid plaques, and tangles formation. Hence,
development of drugs with multiple targets will be effective in the treatment of
AD. The present study aims at evaluation of the neuroprotective effect of
Gelidiella acerosa against amyloid beta 25-35 (Abeta 25-35) induced toxicity in
PC12 cells. The antioxidative effect was evaluated by monitoring levels of
antioxidant enzymes. Protection against ROS-induced damage was assessed by the
measurement of lipid peroxidation, protein carbonyl content (PCC), 2',7'
dichlorofluorescein diacetate (DCFH-DA) fluorescence, and nitric oxide (NO)
production. The cholinesterase (ChE) inhibitory activity was also evaluated. The
antiapoptotic activity was verified by caspase-3 activity. The results of
antioxidant assays suggest that G. acerosa significantly (P < .05) restores the
levels of antioxidant enzymes. Moreover, the seaweed extract was found to prevent
the formation of intracellular ROS induced by Abeta 25-35 and thereby protects
PC12 cells from macromolecular damage. The study demonstrated that G. acerosa
inhibits ChE activity significantly (P < .05) in PC12 cells. The significant
decrease (P < .05) in the level of caspase-3 activity indicates that the seaweed
has anti-apoptotic activity. Hence, the outcome of this study signifies the
neuroprotective effect of G. acerosa targeting multiple pathological consequences
of AD.
PMID- 29958040
TI - Evaluation of Cycloferin Supplement on Health Parameters in Experimentally
Induced Diabetic Rats with and Without Exogenous Insulin.
AB - Cycloferin is an extract of the chemicals from the Cyclopia species, which grows
only in small areas in the southwest and southeast of South Africa and has been
consumed traditionally as a nourishing tea to treat numerous health issues and
illnesses. Previous studies report that some of the active compounds in
Cycloferin, such as pinitol (a modified sugar) and mangiferin (a glucoside), may
reduce blood sugar levels and therefore may be used as a treatment for diabetes.
Mangiferin, in particular, has been shown to stimulate carbohydrate oxidation and
alleviate some effects of insulin resistance and hyperglycemia. Other active
components of Cycloferin include flavones, isoflavones, coumestans, luteolin, 4
hydroxycinnamic acid, polyphenols, and xanthones. These active compounds are
antioxidants, which can enhance glucose breakdown, lower blood lipids, and reduce
the number of highly reactive compounds known as free radicals, which can alter
cellular structure and function when present in large amounts. In this study, we
explored the ameliorative effects of Cycloferin by treating streptozotocin- (STZ)
injected rats with Cycloferin and evaluating its long-term and short-term effect
on blood glucose levels and kidney and liver conditions of the diabetic-rendered
rats. Our results demonstrated the ability of Cycloferin to both lower the blood
glucose levels and reduce evidence of damage in kidney and liver in diabetic rats
with and without exogenous insulin treatment for partial control of diabetic
state.
PMID- 29958041
TI - The "Jay-Dar" Phenomenon: Individuals Discriminate Cannabis Users from Nonusers
Based Upon a Photograph.
AB - OBJECTIVE: With increasing legalization of medicinal and recreational cannabis,
use is on the rise. Research suggests individuals may be able to guess cannabis
user status based upon appearance; however, these findings utilized a small
sample of photographs that was not balanced on user status or gender. Further, no
studies examined whether raters with cannabis experience are better at judging
others' cannabis use, or what physical features they use to make these judgments.
This study explored these factors using a larger, balanced photograph database.
METHOD: An American sample (n = 249, 48.6% female, mean age = 35.19 years) rated
36 photographs (18 cannabis users, 18 nonusers) balanced on gender and age on the
likelihood that the photographed individuals use cannabis, producing 8964
ratings. Respondents also reported physical features considered in their ratings,
as well as their own cannabis use history. RESULTS: As hypothesized, photographs
of users received higher ratings on the Marijuana Use Likelihood Index relative
to nonusers. Further, results revealed a gender by rater user status interaction,
indicating that raters with no previous cannabis experience rated males higher
than females, while raters with cannabis experience did not demonstrate this
rating discrepancy. Cannabis use explained over 9% of the variance in ratings
across all photographs. CONCLUSIONS: Results suggest individuals do rate cannabis
users as more likely to be users, relative to nonusers, based upon appearance
alone. These findings have important implications, not only for research on
chronic cannabis use effects, but also for social and achievement factors such as
potential stigma.
PMID- 29958042
TI - Intent to Refer: Exploring Bias Toward Specific Medication-Assisted Treatments by
Community Corrections Employees.
AB - BACKGROUND: As opioid use increases in the United States, especially in the
correctional population, the most effective treatment approaches need to be
utilized. Research has shown that medication-assisted treatment (MAT) provides
better outcomes than traditional treatment approaches alone, but is underutilized
among correctional-supervised populations. OBJECTIVE: This article looks at how
previously identified barriers to implementing MAT can create potential biases
regarding the intent to refer individuals to either buprenorphine or methadone
among treatment and correctional staff within community corrections. The varying
advantages of each medication are discussed to highlight the importance of
individualized treatment planning. METHODS: Data were collected from 959
treatment specialists and community-corrections officers between 2010 and 2013.
The participants were employed by one of 20 community corrections agencies that
were selected and randomized within a cluster design. The data were part of a
larger study that tested how the experimental condition of organizational
linkages impacted the use of MAT in the criminal justice system. In order to
analyze the data, multinomial logistic regression was used. RESULTS: Results
showed that some community corrections employees were likely to refer clients to
use methadone, but not buprenorphine (or vice versa) which was influenced by work
setting, level of education, training, and negative perceptions of MAT as a
substitute addiction. However, these biases could be minimized by proper
training. CONCLUSION: These findings suggest that proper training should be
mandatory for these employees and include information about various MATs while
also addressing the negative perception that MAT is a substitute addiction.
PMID- 29958043
TI - Religiosity and Alcohol Use: Is Religiosity Important for Abstention and
Consumption Levels in the Second Half of Life?
AB - OBJECTIVE: The aim of this study was to investigate the relative role of
religiosity for alcohol abstention and consumption levels among individuals aged
40 years or above. METHOD: A two-wave prospective survey was conducted among
Norwegians aged 40 to 80 years (Time 1 in 2002/2003, and Time 2 in 2007/2008).
The analytical sample of this study constituted those who responded to the
questionnaire survey at both time points (n = 2671). RESULTS: The findings showed
that religiousity was strongly associated with abstention and less consumption
while adjusting for demographics and health variables. The results also reflected
that females and those with higher age were more likely to abstain from alcohol
than males and those with lower age, respectively. Individuals with high
education were less likely to abstain than those with basic education. Females
and those with high age also reflected less alcohol consumption than males and
individuals of lower age, respectively. Further, people who were married or with
a registered partner consumed less alcohol than people who were not married or
with a registered partner. High education and good physical health was associated
with higher consumption. The main results were consistent across prospective and
cross-sectional models. CONCLUSION: Religiosity seems to be important both for
abstention and alcohol consumption levels in the second half of life.
PMID- 29958044
TI - Micronutrient Fortification at Child-Care Centers Reduces Anemia in Young
Children.
AB - The aim of this study was to evaluate the effectiveness of NutriSUS micronutrient
fortification, in infants aged 12-36 months, for the prophylaxis and treatment of
iron deficiency anemia. In this cluster-randomized clinical trial study, we
evaluated infants aged 12-36 months. Length of intervention was 12 weeks.
Children were cluster randomized to either NutriSUS micronutrient fortification
(Group A) or control (Group B). Primary outcome variables were change in
hemoglobin concentration and anemia prevalence. Two biochemical evaluations were
performed to determine hemoglobin concentrations: before and after intervention.
This study was conducted in eight child-care centers located within the urban
perimeter of the municipality of Sobral, Ceara, in the northeast of Brazil. For
Group A, baseline mean hemoglobin concentration was 11.4 +/- 1.01 g/dL; after
intervention it was 11.9 +/- 0.90 g/dL (p = .006); 15 of 20 participants who were
anemic at baseline had normal Hb levels after intervention. Number needed to
treat = 2. In group B, mean baseline hemoglobin was 11.9 +/- 0.89 g/dL; after
intervention it was 12.2 +/- 0.92 g/dL (p = .58); 4 of 5 participants who were
anemic at baseline remained anemic after intervention. In our study, NutriSUS
micronutrient fortification provided a beneficial effect on Hb values, reducing
the prevalence of anemia. However, further studies are necessary to confirm the
effectiveness of this intervention in populations on a larger scale.
PMID- 29958045
TI - Long-Term Outcomes of Oral Anti-Tubercular Therapy in Patient with Tubercular
Dacryoadenitis: A Case Series.
AB - PURPOSE: To describe the clinico-radiological features and long-term outcomes in
patients with tubercular dacryoadenitis (TbD) Methods: Retrospective,
observational study of TbD patients who underwent a thorough clinical
examination, orbital imaging study, and tailored ancillary investigations.
Polymerase chain reaction (PCR) and microscopy were done in specific cases. A 4
drug anti-tubercular therapy (ATT) was started and clinical response was
monitored in all. Patients with a minimum follow-up of 6 months "off-ATT" were
included. RESULTS: All patients were women and three presented with pain,
blepharoptosis, and bilateral involvement. In all, ESR was raised, Mantoux test
was positive and orbital imaging revealed enlarged lacrimal gland/s. Positive PCR
and granulomatous inflammation on microscopy were seen in two patients. At a mean
follow-up of 17.25 months, all women responded with no relapse or clinical
recurrence. CONCLUSION: Bilateral lacrimal gland enlargement, positive Mantoux &
PCR with early response to ATT may provide sufficient evidence for diagnosing
TbD.
PMID- 29958046
TI - Putative Effect of Spirulina Extract on Enzyme Activities Participating in Lipid
and Carbohydrate Digestion Processes.
AB - Excessive calorie intake is generally accepted as a primary cause of metabolic
syndrome, and therefore a well-balanced diet and moderate exercise can be
expected to be the most effective measures to avoid the disorder of energy
utilization and storage. Furthermore, as any other way to improve the disorder of
energy balance, it may be effective to delay and lower the digestion and/or
absorption of energy sources, lipids, and carbohydrates. As a primary screening
of effective substances to delay and lower the digestion and absorption processes
among natural materials, the protein-deprived extract was prepared from blue
green algae Spirulina platensis, and the effect of this extract on lipase and
alpha-glucosidase activities was examined. The extract was shown to inhibit
lipase activity but not alpha-glucosidase activity, thus proposing the
possibility that the extract prevented the postprandial elevation of blood
triglyceride (TG) levels as a result of reducing the digestion and absorption of
lipids in the intestinal tract. Therefore, it seems possible to speculate that
nonprotein components of Spirulina may be able to effectively improve the
disorder of energy balance as a consequence of suppressing the excessive intake
of calories by reducing the absorption of lipids in patients with metabolic
syndrome.
PMID- 29958047
TI - Reply to: "Crowell et al. Idiopathic Central Nervous System Inflammatory Disease
in the Setting of HLA-B27 Uveitis".
PMID- 29958048
TI - Sex Differences in Traditional and Nontraditional Risk Factors for Obstructive
Coronary Artery Disease in Stable Symptomatic Patients.
AB - BACKGROUND: There have been limited data on sex-specific risk factors for
coronary artery disease (CAD) in patients with stable chest pain. This study was
performed to investigate whether risk factors for CAD differ by sex in stable
symptomatic patients. METHODS: Data were obtained from a nation-wide registry,
enrolling 1025 patients (age, 62.0 +/- 11.0 years, 587 women) with chest pain who
underwent elective invasive coronary angiography under the suspicion of CAD.
RESULTS: A total of 373 patients (36.4%) had obstructive CAD (>=50% stenosis)
(men vs. women: 33.8% vs. 38.3%, p = 0.135). In men, univariate analyses showed
that age, renal function, total cholesterol, low-density lipoprotein cholesterol,
triglyceride, C-reactive protein (CRP), left ventricular (LV) systolic function,
and septal annular velocity of LV (e') were significantly associated with the
presence of obstructive CAD. Among these factors, a high CRP level (>=0.50 mg/dL)
was an independent predictor of CAD in multivariable analysis (odds ratio [OR],
2.93; 95% confidence interval [CI], 1.26-6.82; p = 0.012). In women, univariate
analyses showed that age, waist circumference, heart rate, hypertension, diabetes
mellitus, low high-density lipoprotein cholesterol, LV systolic function, LV mass
index, e' velocity, E/e', and left atrial size were significantly associated with
the presence of obstructive CAD. Among these factors, lower e' velocity (<6.35
cm/s) was an independent predictor of CAD in multivariable analysis (OR, 2.38;
95% CI, 1.21-4.70; p = 0.012). CONCLUSIONS: Among patients with stable chest
pain, inflammation and LV diastolic dysfunction are independently associated with
obstructive CAD in men and women, respectively.
PMID- 29958049
TI - Acute Effect of Oral N-Acetylcysteine on Muscle Soreness and Exercise Performance
in Semi-Elite Rugby Players.
AB - N-acetylcysteine (NAC) supplementation may enhance performance and reduce
soreness from acute, repeated-sprint, high-intensity exercise. Our aim was to
investigate whether semi-elite rugby union athletes may benefit. In a randomized
block design, 17 semi-elite male rugby players were assigned to receive either 1
g oral NAC (n = 8) or placebo (n = 9) for six days. The mean percentage effect of
NAC on exercise performance was assessed through completion of a broken bronco
exercise test on days 5 and 6 of supplementation. Players self-reported muscle
soreness and tolerability to supplements using a modified Muscle Pain and
Treatment Satisfaction Questionnaire throughout the supplement duration. NAC
produced a likely beneficial performance effect on maximum shuttle sprint time
(2.4%; 90% confidence limit +/- 4.8%) but was unclear on total time during back
to-back broken bronco tests compared to placebo. NAC had a likely protective
effect on subjective muscle soreness during days 1-4 of supplementation (-19% +/-
27%) but a very likely harmful effect on days 5 and 6 of supplementation (71% +/-
59%). Daily supplementation with 1 g of oral NAC for six days produced no adverse
side effects, reduced muscle soreness after one bout of damaging exercise, but
increased soreness following the second bout. The performance effects were
generally unclear apart from maximal sprint time.
PMID- 29958050
TI - Dialectical Behavior Therapy Skills Training in Alcohol Dependence Treatment:
Findings Based on an Open Trial.
AB - BACKGROUND: Dialectical behavior therapy (DBT) has demonstrated efficacy in
treating disorders such as alcohol dependence that are characterized by emotional
dysregulation. Preliminary evidence has revealed the feasibility of DBT skills
training (ST) as a stand-alone treatment for such disorders. Although emotional
dysregulation plays a significant role in alcohol dependence, there are no
previous reports of using DBT-ST to treat it. OBJECTIVES: The aim of this study
was to evaluate the duration of abstinence and changes in emotional regulation in
a 3-month DBT-ST program for alcohol-dependent patients and to look for relations
between abstinence and emotional regulation. METHODS: We administered the
Difficulties in Emotion Regulation Scale (DERS) and used urine toxicology
screening to monitor alcohol/substance intake among the 244 subjects admitted to
the program. RESULTS: Among the 157 patients who completed the treatment, 73.2%
were abstinent at the end of the program, and their emotional regulation
improved. Improvement was independent of the initial severity of both alcohol use
and emotional dysregulation. For substance use outcomes, we found a partial
mediation role of improved emotional regulation. CONCLUSIONS: This is the first
open trial to show improved alcohol-related behavior and emotional regulation in
alcohol-dependent patients treated with DBT-ST and to posit a partial but
significant relation between improved emotional regulation and alcohol use
outcomes. In the treatment of alcohol dependence, emotional regulation may be a
relevant factor for therapists to consider.
PMID- 29958051
TI - Malnutrition and Associated Disorders in Tuberculosis and Its Therapy.
AB - Tuberculosis (TB) has become the most important infectious disease to see
resurgence worldwide. In 2014, there were 9.6 million documented cases worldwide
with a mortality of almost 1.5 million (Global Tuberculosis Report 2014). One of
the Millennium Development Goals set by the United Nations was the reversal of
the TB epidemic, which has been achieved worldwide with an 18% lower incidence of
TB globally compared to the incidence in the year 2000. Though efficient
intervention has brought down the relative incidence and mortality of TB
globally, the fact remains that one third of the world population has latent TB
infection, and 10% of people with latent TB infection develop active TB at some
point in their life (The Facts about Tuberculosis 1995). Risk factors that prompt
the reactivation of latent TB into active TB are a compromised immune system,
HIV, malnutrition, and use of tobacco. In developing and underdeveloped
economies, malnutrition and undernutrition play a major role in subverting the
immune system and reactivating the latent TB infection. Undernutrition is one of
the major factors in India and Southeast Asia leading to an increase in TB
infections. Once tuberculosis sets in, it leads to an increase in metabolism and
a decrease in appetite that compounds the already present malnutrition. Drawing
on previous studies, we have aimed at understanding the relationship between
malnutrition and TB infection and making minimal recommendations for corrective
action.
PMID- 29958052
TI - Identification of Cosalane as an Inhibitor of Human and Murine CC-Chemokine
Receptor 7 Signaling via a High-Throughput Screen.
AB - CC-chemokine receptor 7 (CCR7) is a G protein-coupled receptor expressed on a
variety of immune cells. CCR7 plays a critical role in the migration of
lymphocytes into secondary lymphoid tissues. CCR7 expression, however, has been
linked to numerous disease states. Due to its therapeutic relevance and absence
of available CCR7 inhibitors, we undertook a high-throughput screen (HTS) to
identify small-molecule antagonists of the receptor. Here, we describe a robust
HTS approach using a commercially available beta-galactosidase enzyme fragment
complementation system and confirmatory transwell chemotaxis assays. This work
resulted in the identification of several compounds with activity against CCR7.
The most potent of these was subsequently determined to be cosalane, a
cholesterol derivative previously designed as a therapeutic for human
immunodeficiency virus. Cosalane inhibited both human and murine CCR7 in response
to both CCL19 and CCL21 agonists at physiologic concentrations. Furthermore,
cosalane produced durable inhibition of the receptor following a cellular
incubation period with subsequent washout. Overall, our work describes the
development of an HTS-compatible assay, completion of a large HTS campaign, and
demonstration for the first time that cosalane is a validated CCR7 antagonist.
These efforts could pave the way for new approaches to address CCR7-associated
disease processes.
PMID- 29958053
TI - The Effects of Curcumin on Serum Heat Shock Protein 27 Antibody Titers in
Patients with Metabolic Syndrome.
AB - Metabolic syndrome (MetS) is associated with an increased risk of cardiovascular
disease and diabetes mellitus. Inflammation and oxidant stress are features of
MetS that can enhance the expression and release of heat shock proteins (Hsps),
including the small heat shock protein, Hsp 27, and that may subsequently lead to
the production of Hsp27 antibodies (anti-Hsp 27). Curcumin is an anti
inflammatory and antioxidant phytochemical that may ameliorate these features of
MetS. We investigated the effects of unformulated curcumin and phospholipidated
curcumin on antibody titers to heat shock protein 27 (anti-Hsp 27) in patients
with MetS. A randomized double-blind, placebo-controlled clinical trial design
was used in 120 patients with MetS (diagnosed according to the International
Diabetes Federation [IDF] criteria). Participants were randomly allocated to 3
groups, with 40 individuals per group, that received either 1 g/d curcumin,
phospholipidated curcumin, or a placebo for 6 weeks. The changes in serum
concentrations of anti-Hsp 27 did not differ significantly between study groups
(p = .283). There was no significant difference between baseline and end-of-trial
concentrations of anti-Hsp 27 in groups supplemented with curcumin (p = .177),
phospholipidated curcumin (p = .798), or placebo (p = .663). Curcumin
supplementation (1 g/d) has no significant effects on anti-Hsp 27 titers in
patients with MetS.
PMID- 29958054
TI - Antibacterial Activity of Semenovia suffruticosa (Essential Oil) Against
Pathogenic Bacteria and Determination of Chemical Composition of Essential Oils
by Gas Chromatography-Mass Spectrometry Analysis in Four Regions of Kerman.
AB - The use of medicinal plants has been considered due to increasing bacterial
resistance to antibiotics. Semenovia suffruticosa is a plant with high potential
in medicine. The aim of this study was to evaluate the antibacterial activities
and gas chromatography-mass spectrometry (GC-MS) analyses of the essential oil of
S. suffruticosa from four regions in Kerman: Hezar Mountain, Laleh Zar, Bidkhan,
and Rabor. The essential oil of this plant was extracted by Clevenger. The
antibacterial activities were evaluated against three Gram-negative bacteria (P.
aeruginosa, K. pneumonia, Acinetobacter) and three Gram-positive bactria (B.
subtilis, S. aureus, S. pneumoniae). By disk diffusion method, minimum inhibitory
concentration (MIC) and minimum bactericidal concentration (MBC) values were
determined. The composition of essential oil was identified by GC-MS analysis. In
our study, most yield of essential oil of S. suffruticosa was 1.2% from the Laleh
Zar region and the main components were Z-beta-ocimene (25.4%) in Laleh Zar,
linalool (17.7%) in Hezar, Z-beta-ocimene (18.5%) in Bidkhan, and beta-pinene
(10.5%) in the Rabor region. Maximum inhibition zone by the essential oil from
region Bidkhan was observed against K. pneumoniae (30 mm). The MIC value for S.
suffruticosa collected from Laleh Zar was 1.25 mg/ml against S. aureus and S.
pneumonia. The results of this study confirm that the significant antibacterial
effects of S. suffruticosa and make it a valuable compound in essential oils for
pharmaceutical use and a good replacement for chemical antibiotics. Environmental
conditions can result in a difference in yields and components; this can be
considered significant potential for this plant.
PMID- 29958056
TI - Fresh Fruit Juice of Opuntia dillenii Haw. Attenuates Acetic Acid-Induced
Ulcerative Colitis in Rats.
AB - The present study aimed to evaluate the protective effect of fresh fruit juice of
Opuntia dillenii Haw. (FJOD) on acetic acid-induced ulcerative colitis in rats.
Fresh FJOD (2.5 and 5 ml/kg) and sulfasalazine (100 mg/kg) were given orally for
seven consecutive days prior to colitis induction on the eighth day by
intrarectal acetic acid (4% v/v) administration. Macroscopic, clinical activity
scoring, biochemical, and histopathological examinations of colon were used to
assess colonic damage. FJOD and sulfasalazine treatment significantly attenuated
the macroscopic damage, clinical activity score, and wet weight of the colon when
compared to disease control and further showed significantly reduced levels of
myeloperoxidase, malondialdehyde, and serum lactate dehydrogenase and enhanced
colonic levels of reduced glutathione. The protective effect of FJOD may be
attributed to its antioxidant and anti-inflammatory activities in ulcerative
colitis. The observed effects may be due to the presence of phenolics,
flavonoids, and betalains in the fruit juice of Opuntia dillenii.
PMID- 29958055
TI - Vitamin D Decreases Beck Depression Inventory Score in Patients with Mild to
Moderate Ulcerative Colitis: A Double-Blind Randomized Placebo-Controlled Trial.
AB - The prevalence of depression in inflammatory bowel disease (IBD) is significantly
more than in controls. Some studies assessed the link between vitamin D and
depression. The aim of this study was to assess the effect of vitamin D on Beck
Depression Inventory (BDI) score in ulcerative colitis (UC) patients. In this
double-blind randomized controlled trial, 90 mild to moderate UC patients were
assigned to receive a single injection of 300,000 IU vitamin D3 or 1 ml normal
saline as placebo. At baseline and 3 months later, measurements of BDI score and
serum 25-OH-vitamin D3 were done. Data were compared by independent sample t
test, Mann-Whitney U test, and analysis of covariance (ANCOVA). Baseline BDI
scores were not statistically different between the two groups (p = .4); scores
decreased in the vitamin D group after the intervention (p = .023). Further
subgroup analysis regarding baseline serum vitamin D levels and adjusted for
baseline BDIs revealed lowering effect of vitamin D on BDI scores only in
subgroup with baseline serum vitamin D levels equal to or higher than 30 ng/ml (p
< .001). In this study, there was a statistically significant reduction in BDI
score in mild to moderate UC patients 3 months after 300,000 IU vitamin D3
injection. Subgroup analysis showed that patients with sufficient baseline
vitamin D may benefit from supplementation more than vitamin D-deficient
patients, which indicates that higher serum vitamin D levels may be needed for
its antidepressant effect.
PMID- 29958057
TI - Efficacy and Safety of Loteprednol 0.5% and Fluorometholone 0.1% After Strabismus
Surgery in Children.
AB - PURPOSE: To compare the effects of topical loteprednol and fluorometholone in
children who underwent strabismus surgery. METHODS: This is a retrospective
observational case series. A total of 60 Korean children who underwent strabismus
surgery between January 2016 and September 2016 were included. Patients were
prescribed topical loteprednol etabonate 0.5% or fluorometholone 0.1% until 3
weeks after surgery. Four parameters (intraocular pressure [IOP], conjunctival
injection, conjunctival inflammation, and patient discomfort) were assessed every
week for up to 4 weeks after surgery. Main outcome measures were comparison of
parameters between the 2 groups at each following week after surgery. In
addition, factors associated with clinically meaningful IOP elevation were
evaluated. RESULTS: IOP was significantly elevated at the second and third
postoperative week compared with baseline (P = 0.028 and 0.001) in the
loteprednol group but not significantly in the fluorometholone group. The mean
IOP of the loteprednol group at 1 and 3 weeks after surgery were significantly
higher than that of the fluorometholone group (P = 0.032 and 0.017,
respectively). Multivariate analysis revealed that age <=8 years (odds ratio
14.52, 95% confidence interval 1.16-139.05) was associated with IOP >21 mmHg.
There was no significant difference between the 2 groups in patient discomfort,
conjunctival inflammation, and conjunctival injection. CONCLUSIONS: Loteprednol
and fluorometholone showed similar anti-inflammatory effect after strabismus
surgery in children. Loteprednol appeared to have more effect on IOP elevation
than fluorometholone, especially in children <=8 years of age. When treating
young patients with loteprednol, clinicians should be aware of IOP elevation.
PMID- 29958058
TI - Assessment of step accuracy using the Consumer Technology Association standard.
AB - The purpose of this study was to compare the accuracy of commercially-available
physical activity devices when walking and running at various treadmill speeds
using CTA 2056: Physical Activity Monitoring for Fitness Wearables: Step
Counting, standard by the Consumer Technology Association (CTA). Twenty
participants (10 males and 10 females) completed self-paced walking and running
protocols on the treadmill for five minutes each. Eight devices (Apple iWatch
series 1, Fitbit Surge, Garmin 235, Moto 360, Polar A360, Suunto Spartan Sport,
Suunto Spartan Trainer, and TomTom Spark 3) were tested two at a time, one per
wrist. Manual step counts were obtained from video to serve as the benchmark. The
mean absolute percent error (MAPE) was calculated during walking and running.
During walking, three devices: Fitbit Surge (11.20%), Suunto Sport (22.93%), and
TomTom (10.11%) and during running, one device, Polar (10.66%), exceeded the CTA
suggestion of a MAPE < 10%. The Moto 360 had the lowest MAPE of all devices for
both walking and running. The devices tested had higher step accuracy with
running than walking, except for the Polar. Overall, the Apple iWatch series 1,
Moto 360, Garmin, and Suunto Spartan Trainer met the CTA standard for both
walking and running.
PMID- 29958059
TI - Characterization of in vivo biotransformations for trastuzumab emtansine by high
resolution accurate-mass mass spectrometry.
AB - Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) designed for
the treatment of HER2-positive cancers. T-DM1 is composed of the humanized
monoclonal antibody trastuzumab connected to a maytansine derivative cytotoxic
drug, via a nonreducible thioether linker at random lysine residues, and
therefore has a very complex molecular structure. It was anticipated that T-DM1
undergoes biotransformations in circulation. However, there was limited knowledge
on these structural changes due to bioanalytical challenges. Here, we have
investigated the in vivo biotransformations of T-DM1 using a high-resolution
accurate-mass (HR/AM) mass spectrometry approach. Three types of
biotransformations were characterized for T-DM1 in circulation in tumor-bearing
mice, including cysteine or glutathione adduct formation via maleimide exchange,
loss of maytansinol via ester hydrolysis, as well as addition of H2O via linker
drug hydrolysis. These results provide new insights into in vivo catabolism of T
DM1.
PMID- 29958060
TI - Developing Treatments for Antisocial Behavior Among Children: Controlled Trials
and Uncontrolled Tribulations.
AB - The article describes my research on the development and evaluation of
psychosocial treatments for children who engage in extremes of antisocial
behavior (e.g., aggression, property destruction, theft). I begin with my "story"
of how the focus on interventions started as I worked in various settings
(rehabilitation facilities, schools, hospitals, and outpatient clinical services)
and with children, adolescents, and adults. The main stream of treatment research
and findings with antisocial child behavior is highlighted along with tributaries
that led naturally from the outcome research. Our trials are complemented by
tribulations that apply to evidence-based psychosocial interventions more
broadly. Most individuals in need of psychological services in the United States
and worldwide receive no treatment. Much can be done right now with novel models
of treatment delivery that draw on multiple disciplines (e.g., public health,
business, entertainment, economics, robotics and artificial intelligence, and law
and social policy). More research on interventions that do not or cannot reach
most people in need is quite limited in value to me. Finally (and belatedly) my
attention has turned to ways of exerting impact, and for that, evidence-based
interventions are necessary but hardly sufficient.
PMID- 29958061
TI - Efficient expression of recombinant human telomerase inhibitor 1 (hPinX1) in
Pichia pastoris.
AB - PinX1 encoded by a remarkable tumor suppressor gene and located in human
chromosome 8p23 is known as telomerase inhibitor. In recent years, this protein
has been of interest as clinically tumor suppressor. Pichia pastoris expression
system is preferred to produce heterologous proteins and is suitable for
industrial and research purposes. In the present study, human PinX1 gene (hPinX1)
was cloned in E. coli One Shot TOP10 cells and overexpressed in P. pastoris
strain X-33 intracellularly, using a strong AOX (alcohol oxidase) promoter. The
recombinant cells were grown in shaking flask. Induction time, methanol
concentration and initial pH were optimized for obtaining high levels of hPinX1
protein production. Recombinant protein production was confirmed by Western blot
analysis and the relative expression levels of rhPinX1 were quantified. According
to Western blot analysis, molecular mass of produced hPinX1 was determined as
47.5 kDa. At the end of optimization studies, the best fermentation conditions
were determined as induction time 48 h, methanol concentration 3% and initial
culture pH 5.0. This process would be an applicable way for obtaining recombinant
hPinX1 using P. pastoris expression system. This is the first report on
recombinant production of hPinX1 in P. pastoris.
PMID- 29958062
TI - Heterologous recombinant expression of non-originator NISTmAb.
AB - The successful development and regulatory approval of originator and biosimilar
therapeutic proteins requires a systems approach to upstream and downstream
processing as well as product characterization and quality control. Innovation in
process design and control, product characterization strategies, and data
integration represent an ecosystem whose concerted advancement may reduce time-to
market and further improve comparability and biosimilarity programs. The
biopharmaceutical community has made great strides to this end, yet there
currently exists no pre-competitive monoclonal antibody (mAb) expression platform
for open innovation. Here, we describe the development and initial expression of
an intended copy of the NISTmAb using three non-originator murine cell lines. It
was found that, without optimization and in culture flasks, all three cell lines
produce approximately 100 mg mAb per liter of culture. Sodium dodecyl sulfate
polyacrylamide gel electrophoresis, size-exclusion chromatography, nuclear
magnetic resonance spectroscopy, intact mass spectrometry, and surface plasmon
resonance were used to demonstrate that the products of all three cell lines
embody quality attributes with a sufficient degree of sameness to the NISTmAb
Reference Material 8671 to warrant further bioreactor studies, process
improvements and optimization. The implications of the work with regard to pre
competitive innovation to support process design and feedback control,
comparability and biosimilarity assessments, and process analytical technologies
are discussed.
PMID- 29958063
TI - Pneumothorax: Laparoscopic Intraoperative Management During Fundoplication
Facilitates Management of Cardiopulmonary Instability and Surgical Exposure.
AB - INTRODUCTION: Intraoperative pneumothorax may complicate surgery by obscuring
surgical view and cause cardiorespiratory instability during fundoplication with
large hiatus hernia. Proactive intraoperative treatment may reduce conversion and
drain insertion and facilitate timely completion of surgery. MATERIALS AND
METHODS: The authors present effective surgical and anesthetic measures to
alleviate pneumothorax, which are helpful for hemodynamic stability and surgical
visibility. CONCLUSION: Pneumothorax can complicate surgery by reducing surgical
vision and causing cardiorespiratory instability. There is no requirement for
laparoscopic or intercostal drainage. The authors provide various techniques to
control intraoperative pneumothorax.
PMID- 29958064
TI - Prevalence and Molecular Epidemiology of Clinical Isolates of Escherichia coli
and Klebsiella pneumoniae Harboring Extended-Spectrum Beta-Lactamase and
Carbapenemase Genes in Bangladesh.
AB - Spread of Gram-negative bacteria producing extended-spectrum beta-lactamases
(ESBLs) and carbapenemases constitutes a growing challenge in control of
bacterial infections. In this study, prevalence and genetic characteristics of
Escherichia coli and Klebsiella pneumoniae harboring ESBL and/or carbapenemase
genes, with other beta-lactamase/resistance genes, were investigated for a total
of 375 clinical isolates in Mymensingh located in north-central Bangladesh. The
major ESBL gene was blaCTX-M-1 group, which was detected in 33.9% and 51.4% of E.
coli and K. pneumoniae, respectively, with CTX-M-15 gene being dominant. SHV-type
beta-lactamase genes, including newly identified alleles (SHV-201 and SHV-202)
were detected at higher rate in K. pneumoniae (27%). Nine isolates of E. coli
(3.9%) harbored carbapenemase genes; blaNDM-1 (phylogenetic group A-sequence type
2104 (A-ST2104), B2-ST73), blaNDM-5 (A-ST167, B2-ST38/ST2659-related STs), and
blaNDM-7 (B1-ST101/ST224, D-ST6682). AmpC beta-lactamase genes (blaCMY-2, blaCMY
27, and blaCMY-42) were detected in E. coli, which mostly harbored blaCTX-M-15
and plasmid-mediated quinolone resistance (PMQR) determinants (aac6'-Ib-cr, qnrB,
qnrS, qepA, and oqxAB). A new CMY allele (CMY-160) belonging to CMY-2 group was
identified in phylogenetic group D E. coli. Among K. pneumoniae, carbapenemase
gene was detected in three isolates (2%); blaNDM-1 in ST11 and ST1322, and blaOXA
181 in ST43 isolate. As well as higher rate of aac6'-Ib-cr in K. pneumoniae
(39%), PMQR gene oqxAB was also commonly found among isolates analyzed. These
findings indicated spread of blaNDM genes to diverse E. coli clones and emergence
of blaOXA-181 in K. pneumoniae, with increased prevalence of ESBLs represented by
CTX-M-15 in Bangladesh.
PMID- 29958065
TI - Corrigendum.
AB - John-Baptiste A, Schapira MM, Cravens C, et al. The role of decision models in
health care policy: A case study. Med Decis Making. 2016;36(5):666-679. Original
DOI: 10.1177/0272989X16646732 On page 667, in the paragraph beginning "In May
2008..." the article did not fully describe the process of requesting decision
models for the study. A more complete and accurate description is given below:
The coverage and analysis group (CAG) requested a report from The Technology
Assessment Program (TAP) at the Agency for Healthcare Research and Quality
(AHRQ). AHRQ assigned this report to the Cancer Intervention and Surveillance
Network (CISNET) consortium modeling groups. AHRQ staff also provided guidance on
the model approach and inputs and ensured an arms-length relationship with the
Centers for Medicate and Medicaid Services (CMS) and independence of the
researchers.
PMID- 29958066
TI - Marine Environmental Epigenetics.
AB - Marine organisms' persistence hinges on the capacity for acclimatization and
adaptation to the myriad of interacting environmental stressors associated with
global climate change. In this context, epigenetics-mechanisms that facilitate
phenotypic variation through genotype-environment interactions-are of great
interest ecologically and evolutionarily. Our comprehensive review of marine
environmental epigenetics guides our recommendations of four key areas for future
research: the dynamics of wash-in and wash-out of epigenetic effects, the
mechanistic understanding of the interplay of different epigenetic marks and the
interaction with the microbiome, the capacity for and mechanisms of
transgenerational epigenetic inheritance, and the evolutionary implications of
the interaction of genetic and epigenetic features. Emerging insights in marine
environmental epigenetics can be applied to critical issues such as aquaculture,
biomonitoring, and biological invasions, thereby improving our ability to explain
and predict the responses of marine taxa to global climate change. Expected final
online publication date for the Annual Review of Marine Science Volume 11 is
January 3, 2019. Please see http://www.annualreviews.org/page/journal/pubdates
for revised estimates.
PMID- 29958068
TI - Improving the soluble expression of aequorin in Escherichia coli using the
chaperone-based approach by co-expression with artemin.
AB - Escherichia coli is a common host that is widely used for producing recombinant
proteins. However, it is a simple approach for production of heterologous
proteins; the major drawbacks in using this organism include incorrect protein
folding and formation of disordered aggregated proteins as inclusion bodies. Co
expression of target proteins with certain molecular chaperones is a rational
approach for this problem. Aequorin is a calcium-activated photoprotein that is
often prone to form insoluble inclusion bodies when overexpressed in E. coli
cells resulting in low active yields. Therefore, in the present research, our
main aim is to increase the soluble yield of aequorin as a model protein and
minimize its inclusion body content in the bacterial cells. We have applied the
chaperone-assisted protein folding strategy for enhancing the yield of properly
folded protein with the assistance of artemin as an efficient molecular
chaperone. The results here indicated that the content of the soluble form of
aequorin was increased when it was co-expressed with artemin. Moreover, in the co
expressing cells, the bioluminescence activity was higher than the control
sample. We presume that this method might be a potential tool to promote the
solubility of other aggregation-prone proteins in bacterial cells.
PMID- 29958067
TI - Auditory Distraction During Reading: A Bayesian Meta-Analysis of a Continuing
Controversy.
AB - Everyday reading occurs in different settings, such as on the train to work, in a
busy cafeteria, or at home while listening to music. In these situations, readers
are exposed to external auditory stimulation from nearby noise, speech, or music
that may distract them from their task and reduce their comprehension. Although
many studies have investigated auditory-distraction effects during reading, the
results have proved to be inconsistent and sometimes even contradictory. In
addition, the broader theoretical implications of the findings have not always
been explicitly considered. We report a Bayesian meta-analysis of 65 studies on
auditory-distraction effects during reading and use metaregression models to test
predictions derived from existing theories. The results showed that background
noise, speech, and music all have a small but reliably detrimental effect on
reading performance. The degree of disruption in reading comprehension did not
generally differ between adults and children. Intelligible speech and lyrical
music resulted in the biggest distraction. Although this last result is
consistent with theories of semantic distraction, there was also reliable
distraction by noise. It is argued that new theoretical models are needed that
can account for distraction by both background speech and noise.
PMID- 29958069
TI - Structure Based Prediction of Asparagine Deamidation Propensity in Monoclonal
Antibodies.
AB - Identification of asparagine (Asn) sites that are prone to deamidation is
critical for the development of therapeutic monoclonal antibodies (mAbs). Despite
a common chemical degradation pathway, the rates of Asn deamidation can vary
dramatically among different sites, and prediction of the sensitive deamidation
sites is still challenging. In this study, characterization of Asn deamidation
for five IgG1 and five IgG4 mAbs under both normal and stressed conditions
revealed dramatic differences in the Asn deamidation rates. A comprehensive
analysis of the deamidation sites indicated that the deamidation rate differences
could be explained by differences in the local structure conformation, structure
flexibility and solvent accessibility. A decision tree was developed to predict
the deamidation propensity for all Asn sites in IgG mAbs based on the analysis of
these three structural parameters. This decision tree will allow potential Asn
deamidation hot spots to be identified early in development.
PMID- 29958070
TI - Continuum-Based Geometry/Analysis Approach for Flexible and Soft Robotic Systems.
AB - Control and stability of flexible and soft robotic systems (FSRS), which have
complex geometry and experience desirable and undesirable deformations, are of
major concern, particularly when lightweight soft materials are used.
Nonetheless, there is no unified continuum-based geometry/analysis approach that
can be used for the efficient FSRS virtual prototyping and design. The goal of
this article is to propose a new FSRS geometric modeling and analysis methodology
by addressing fundamental virtual prototyping challenges that include: (1)
integration of the robot geometry and analysis; (2) implementation of general and
unconventional material models and actuation forces; (3) use of new concepts for
modeling FSRS joints; and (4) development of efficient and robust algorithms for
the FSRS virtual prototyping. To address these challenges, the finite element
(FE) absolute nodal coordinate formulation (ANCF) and multibody system
computational algorithms are used. ANCF FEs allow for modeling arbitrarily large
and coupled displacements, correctly capture complex geometries, allow for
implementing general and nonconventional material models, provide accurate
definitions of conventional and nonconventional actuation forces, lead to a
constant inertia matrix that defines optimally sparse matrix structure of the
dynamic equations, and allow for exploiting new geometry concepts to define
linear and more general joint constraints instead of the less general and
nonlinear joint constraints currently used for robot systems. Using the general
structure of the FSRS nonlinear dynamic equations of motion, a nonmodal continuum
based approach can be developed and used to correctly capture the FSRS complex
geometry and large deformations.
PMID- 29958071
TI - Corrigendum.
PMID- 29958072
TI - Plant-Parasitic Nematodes and Food Security in Sub-Saharan Africa.
AB - Sub-Saharan Africa (SSA) is a region beset with challenges, not least its ability
to feed itself. Low agricultural productivity, exploding populations, and
escalating urbanization have led to declining per capita food availability. In
order to reverse this trend, crop production systems must intensify, which brings
with it an elevated threat from pests and diseases, including plant-parasitic
nematodes. A holistic systems approach to pest management recognizes disciplinary
integration. However, a critical under-representation of nematology expertise is
a pivotal shortcoming, especially given the magnitude of the threat nematodes
pose under more intensified systems. With more volatile climates, efficient use
of water by healthy root systems is especially crucial. Within SSA, smallholder
farming systems dominate the agricultural landscape, where a limited
understanding of nematode problems prevails. This review provides a synopsis of
current nematode challenges facing SSA and presents the opportunities to overcome
current shortcomings, including a means to increase nematology capacity.
PMID- 29958073
TI - Sclerotinia sclerotiorum: An Evaluation of Virulence Theories.
AB - Oxalic acid production in Sclerotinia sclerotiorum has long been associated with
virulence. Research involving UV-induced, genetically undefined mutants that
concomitantly lost oxalate accumulation, sclerotial formation, and pathogenicity
supported the conclusion that oxalate is an essential pathogenicity determinant
of S. sclerotiorum. However, recent investigations showed that genetically
defined mutants that lost oxalic acid production but accumulated fumaric acid
could cause disease on many plants and substantiated the conclusion that acidic
pH, not oxalic acid per se, is the necessary condition for disease development.
Critical evaluation of available evidence showed that the UV-induced mutants
harbored previously unrecognized confounding genetic defects in saprophytic
growth and pH responsiveness, warranting reevaluation of the conclusions about
virulence based on the UV-induced mutants. Furthermore, analyses of the evidence
suggested a hypothesis for the existence of an unrecognized regulator responsive
to acidic pH. Identifying the unknown pH regulator would offer a new avenue for
investigating pH sensing/regulation in S. sclerotiorum and novel targets for
intervention in disease control strategies.
PMID- 29958074
TI - Fitness Penalties in the Evolution of Fungicide Resistance.
AB - The evolution of resistance poses an ongoing threat to crop protection. Fungicide
resistance provides a selective advantage under fungicide selection, but
resistance-conferring mutations may also result in fitness penalties, resulting
in an evolutionary trade-off. These penalties may result from the functional
constraints of an evolving target site or from the resource allocation costs of
overexpression or active transport. The extent to which such fitness penalties
are present has important implications for resistance management strategies,
determining whether resistance persists or declines between treatments, and for
resistance risk assessments for new modes of action. Experimental results have
proven variable, depending on factors such as temperature, nutrient status,
osmotic or oxidative stress, and pathogen life-cycle stage. Functional genetics
tools allow pathogen genetic background to be controlled, but this in turn raises
the question of epistatic interactions. Combining fitness penalties under various
conditions into a field-realistic scenario poses an important future challenge.
PMID- 29958075
TI - The Changing Face of Bacterial Soft-Rot Diseases.
AB - Bacterial soft rot is a disease complex caused by multiple genera of gram
negative and gram-positive bacteria, with Dickeya and Pectobacterium being the
most widely studied soft-rot bacterial pathogens. In addition to soft rot, these
bacteria also cause blackleg of potato, foot rot of rice, and bleeding canker of
pear. Multiple Dickeya and Pectobacterium species cause the same symptoms on
potato, complicating epidemiology and disease resistance studies. The primary
pathogen species present in potato-growing regions differs over time and space,
further complicating disease management. Genomics technologies are providing new
management possibilities, including improved detection and biocontrol methods
that may finally allow effective disease management. The recent development of
inbred diploid potato lines is also having a major impact on studying soft-rot
pathogens because it is now possible to study soft-rot disease in model plant
species that produce starchy vegetative storage organs. Together, these new
discoveries have changed how we face diseases caused by these pathogens.
PMID- 29958076
TI - Multifaceted Impacts of Bacteriophages in the Plant Microbiome.
AB - Plant-associated bacteria face multiple selection pressures within their
environments and have evolved countless adaptations that both depend on and shape
bacterial phenotype and their interaction with plant hosts. Explaining bacterial
adaptation and evolution therefore requires considering each of these forces
independently as well as their interactions. In this review, we examine how
bacteriophage viruses (phages) can alter the ecology and evolution of plant
associated bacterial populations and communities. This includes influencing a
bacterial population's response to both abiotic and biotic selection pressures
and altering ecological interactions within the microbiome and between the
bacteria and host plant. We outline specific ways in which phages can alter
bacterial phenotype and discuss when and how this might impact plant-microbe
interactions, including for plant pathogens. Finally, we highlight key open
questions in phage-bacteria-plant research and offer suggestions for future
study.
PMID- 29958077
TI - Getting connected: Intergroup contact on Facebook.
AB - One correlational study examined whether virtual contact via Facebook is
positively related to intergroup relations. The followers of two online campaigns
from Iran and Israel-whose countries have been in a politically hostile
relationship since the 1980s-indicated the amount of direct and indirect virtual
(Facebook) and real-life outgroup contact they have had, a number of quality and
affective judgments about that contact, and completed an affective prejudice
measure about the respective outgroup. Overall, contact was negatively associated
with affective prejudice, providing support for the contact hypothesis in a
specific and exclusively virtual setting with citizens of hostile nations.
Previously experienced real-life contact did not moderate the results, suggesting
that virtual contact has an independent link to positive outgroup attitudes.
PMID- 29958079
TI - Genetics of guanylyl cyclase pathways in the cochlea and their influence on
hearing.
AB - Although hearing loss is the most common sensory deficit in Western societies,
there are no successful pharmacological treatments for this disorder. Recent
experiments have demonstrated that manipulation of intracellular cyclic guanosine
monophosphate (cGMP) concentrations can have both beneficial and harmful effects
on hearing. In this review, we will examine the role of cGMP as a key second
messenger involved in many aspects of cochlear function and discuss the known
functions of downstream effectors of cGMP in sound processing. The nitric oxide
stimulated soluble guanylyl cyclase system (sGC) and the two natriuretic peptide
stimulated particulate GCs (pGCs) will be more extensively covered because they
have been studied most thoroughly. The cochlear GC systems are attractive targets
for medical interventions that improve hearing while simultaneously representing
an under investigated source of sensorineural hearing loss.
PMID- 29958078
TI - Identification of nine novel loci related to hematological traits in a Japanese
population.
AB - Recent genome-wide association studies have identified various genetic variants
associated with hematological traits. Although it is possible that quantitative
data of hematological traits are varied among the years examined, conventional
genome-wide association studies have been conducted in a cross-sectional manner
that measures traits at a single point in time. To address this issue, we have
traced blood profiles in 4,884 Japanese individuals who underwent annual health
check-ups for several years. In the present study, longitudinal exome-wide
association studies were conducted to identify genetic variants related to 13
hematological phenotypes. The generalized estimating equation model showed that a
total of 67 single nucleotide polymorphisms (SNPs) were significantly [false
discovery rate (FDR) of <0.01] associated with hematological phenotypes. Of the
67 SNPs, nine SNPs were identified as novel hematological markers: rs4686683 of
SENP2 for red blood cell count (FDR = 0.008, P = 5.5 * 10-6); rs3917688 of SELP
for mean corpuscular volume (FDR = 0.005, P = 2.4 * 10-6); rs3133745 of C8orf37
AS1 for white blood cell count (FDR = 0.003, P = 1.3 * 10-6); rs13121954 at
4q31.2 for basophil count (FDR = 0.007, P = 3.1 * 10-5); rs7584099 at 2q22.3 (FDR
= 2.6 * 10-5, P = 8.8 * 10-8), rs1579219 of HCG17 (FDR = 0.003, P = 2.0 * 10-5),
and rs10757049 of DENND4C (FDR = 0.008, P = 5.6 * 10-5) for eosinophil count;
rs12338 of CTSB for neutrophil count (FDR = 0.007, P = 2.9 * 10-5); and rs395967
of OSMR-AS1 for monocyte count (FDR = 0.008, P = 3.2 * 10-5).
PMID- 29958080
TI - A mini review: Proteomics approaches to understand disused vs. exercised human
skeletal muscle.
AB - Immobilization, bed rest, or denervation leads to muscle disuse and subsequent
skeletal muscle atrophy. Muscle atrophy can also occur as a component of various
chronic diseases such as cancer, AIDS, sepsis, diabetes, and chronic heart
failure or as a direct result of genetic muscle disorders. In addition to this
atrophic loss of muscle mass, metabolic deregulation of muscle also occurs. In
contrast, physical exercise plays a beneficial role in counteracting disuse
induced atrophy by increasing muscle mass and strength. Along with this, exercise
can also reduce mitochondrial dysfunction and metabolic deregulation. Still,
while exercise causes valuable metabolic and functional adaptations in skeletal
muscle, the mechanisms and effectors that lead to these changes such as increased
mitochondria content or enhanced protein synthesis are not fully understood.
Therefore, mechanistic insights may ultimately provide novel ways to treat disuse
induced atrophy and metabolic deregulation. Mass spectrometry (MS)-based
proteomics offers enormous promise for investigating the molecular mechanisms
underlying disuse and exercise-induced changes in skeletal muscle. This review
will focus on initial findings uncovered by using proteomics approaches with
human skeletal muscle specimens and discuss their potential for the future study.
PMID- 29958081
TI - Influenza virus infection modulates the death receptor pathway during early
stages of infection in human bronchial epithelial cells.
AB - Host-viral interaction occurring throughout the infection process between the
influenza A virus (IAV) and bronchial cells determines the success of infection.
Our previous studies showed that the apoptotic pathway triggered by the host
cells was repressed by IAV facilitating prolonged survival of infected cells. A
detailed understanding on the role of IAV in altering the cell death pathway
during early-stage infection of human bronchial epithelial cells (HBEpCs) is
still unclear. We investigated the gene expression profiles of IAV-infected vs.
mock-infected cells at the early stage of infection with a PCR array for death
receptor (DR) pathway. At early stages infection (2 h) with IAV significantly
upregulated DR pathway genes in HBEpCs, whereas 6 h exposure to IAV resulted in
downregulation of the same genes. IAV replication in HBEpCs decreased the levels
of DR pathway genes including TNF-receptor superfamily 1, Fas-associated death
domain, caspase-8, and caspase-3 by 6 h, resulting in increased survival of
cells. The apoptotic cell population decreased in 6 h compared with the 2 h
exposure to IAV. The PCR array data were imported into Ingenuity Pathway Analysis
software, resulting in confirmation of the model showing significant modulation
of the DR pathway. Our data indicate that a significant transcriptional
regulation of apoptotic, necrotic, and DR genes occur at early and late hours of
infection that are vital in modulating the survival of host cells and replication
of IAV. These data may have provided a likely roadmap for translational
approaches targeting the DR pathway to enhance apoptosis and inhibit replication
of the virus.
PMID- 29958082
TI - The Discovery of the Antiviral Resistance Gene Mx: A Story of Great Ideas, Great
Failures, and Some Success.
AB - The discovery of the Mx gene-dependent, innate resistance of mice against
influenza virus was a matter of pure chance. Although the subsequent analysis of
this antiviral resistance was guided by straightforward logic, it nevertheless
led us into many blind alleys and was full of surprising turns and twists.
Unexpectedly, this research resulted in the identification of one of the first
interferon-stimulated genes and provided a new view of interferon action. It also
showed that in many species, MX proteins have activities against a broad range of
viruses. To this day, Mx research continues to flourish and to provide insights
into the never-ending battle between viruses and their hosts.
PMID- 29958083
TI - The IMMUNE-ASSOCIATED NUCLEOTIDE-BINDING 9 Protein Is a Regulator of Basal
Immunity in Arabidopsis thaliana.
AB - A robust regulation of plant immune responses requires a multitude of positive
and negative regulators that act in concert. The immune-associated nucleotide
binding (IAN) gene family members are associated with immunity in different
organisms, although no characterization of their function has been carried out to
date in plants. In this work, we analyzed the expression patterns of IAN genes
and found that IAN9 is repressed upon pathogen infection or treatment with immune
elicitors. IAN9 encodes a plasma membrane-localized protein that genetically
behaves as a negative regulator of immunity. A novel ian9 mutant generated by
CRISPR/Cas9 shows increased resistance to Pseudomonas syringae, while transgenic
plants overexpressing IAN9 show a slight increase in susceptibility. In vivo
immunoprecipitation of IAN9-green fluorescent protein followed by mass
spectrometry analysis revealed that IAN9 associates with a previously
uncharacterized C3HC4-type RING-finger domain-containing protein that we named
IAN9-associated protein 1 (IAP1), which also acts as a negative regulator of
basal immunity. Interestingly, neither ian9 or iap1 mutant plants show any
obvious developmental phenotype, suggesting that they display enhanced inducible
immunity rather than constitutive immune responses. Because both IAN9 and IAP1
have orthologs in important crop species, they could be suitable targets to
generate plants more resistant to diseases caused by bacterial pathogens without
yield penalty.
PMID- 29958084
TI - The concept of death in children aged from 9 to 11 years: Evidences through
inductive and deductive analysis of drawings.
AB - The objective of the research was to analyze children's conceptualization of
death through drawings, using a mixed approach, which combines deductive and
inductive qualitative analysis. The sample consisted of 99 children aged 9-11
years, who were asked to elaborate a drawing about their idea of death and to
explain it to the researchers. Drawings were coded basing on Tamm and Granqvist's
model (deductive analysis) and codes and categories were created and modified
(inductive analysis). Three main categories were identified in the analysis and
four sub-categories were modified and/or created: causes of death, good death,
anxiety-fear and symbolization.
PMID- 29958085
TI - All-cause and cause-specific mortality rates of patients treated for alcohol use
disorders: A meta-analysis.
AB - BACKGROUND: Although alcohol use disorders (AUDs) are known to increase the
relative risk of all-cause and some cause-specific mortality, the absolute
mortality rates of the AUD population are unknown. Such knowledge would benefit
planners of the provision of services for this population, including in
prioritizing the identification and/or treatment of diseases likely to cause
their death. METHODS: We conducted a systematic review of studies in English,
reporting the cause-specific mortality rates among people treated for AUDs.
Number of deaths by cause and total person-years of follow-up were extracted. All
cause and cause-specific mortality rates per 1000 person-years were meta-analyzed
assuming random effects. RESULTS: Thirty-one studies were included. Participants
were mainly middle-aged males. The quality of studies was generally good. A total
of 6768 all-cause deaths in 276,990.7 person-years of follow-up (36,375 patients)
were recorded, and the pooled all-cause mortality rate was 27.67/1000 person
years (py) (95% confidence interval [CI]: 23.9, 32.04). The most common cause of
death in the AUD population was cardiovascular disease (CVD) (6.9/1000 py; 95%
CI: 5.61, 8.49), followed by gastrointestinal deaths (5.63/1000 py; 95% CI: 4.1,
7.74), unnatural deaths (4.95/1000 py; 95% CI: 4.01, 6.09)), neoplasms,
respiratory diseases, and substance use disorders. CONCLUSIONS: Patients with
AUDs have increased rates of all-cause and cause-specific mortality compared with
the general population. Like the general population, they are most likely to die
of CVD. In contrast to the general population, gastrointestinal and unnatural
deaths are the next most common causes of death. We believe these facts should be
considered when planning health care services for patients with AUDs.
PMID- 29958086
TI - Improving undergraduate competence in multicultural gerontology practice with
fresh pedagogies: a digital storytelling case example.
AB - Building on a student-led digital storytelling project, the author suggests that
expanding definitions of two core constructs of social work education and
practice, experiential learning and cultural competence, can improve outcomes for
diverse older clients by increasing competence in multicultural gerontology
practice. Using a variety of media, digital storytelling focuses on stories that
are not often heard, like those of diverse older adults. Student-led projects
provide opportunities for students to engage with experiential learning, a high
impact pedagogy. Beyond describing a one-semester digital storytelling project
that occurred in an undergraduate gerontology practice course, the article shares
findings from the project's evaluation. The evaluation yielded recommendations,
such as encouraging social work faculty to provide opportunities for experiential
learning across the curriculum, and improving competence in multicultural
gerontology practice through creative pedagogies. Ultimately, the author suggests
that fresh pedagogical approaches that expand core social work constructs can
improve outcomes for diverse older adults by promoting multicultural gerontology
practice competence.
PMID- 29958087
TI - Telemedicine Is Associated with Faster Diagnostic Imaging in Stroke Patients: A
Cohort Study.
AB - BACKGROUND: Meeting time goals for patients with time-sensitive conditions can be
challenging in rural emergency departments (EDs), and adopting policies is
critical. ED-based telemedicine has been proposed to improve quality and
timeliness of care in rural EDs. INTRODUCTION: The objective of this study was to
test the hypothesis that diagnostic testing in telemedicine-supplemented ED care
for patients with myocardial infarction (MI) and stroke would be faster than
nontelemedicine care in rural EDs. MATERIALS AND METHODS: This observational
cohort study included all ED patients with MI or stroke in 19 rural critical
access hospitals served by a single real-time contract-based telemedicine
provider in the upper Midwest (2007-2015). The primary outcome for the MI cohort
was time-to-electrocardiogram (EKG) and for the stroke cohort was time-to-head
computed tomography (CT) interpretation. To measure the relationship between
telemedicine and timeliness parameters, generalized estimating equations models
were used, clustering on presenting hospital. RESULTS: Of participating ED
visits, 756 were included in the MI cohort (29% used telemedicine) and 140 were
included in the stroke cohort (30% used telemedicine). Time-to-EKG did not differ
when telemedicine was used (1% faster, 95% confidence interval [CI] -4% to 7%),
or after telemedicine was implemented (4% faster, 95% CI -3% to 10%). Head CT
interpretation was faster for telemedicine cases (15% faster, 95% CI 4-26%). No
differences were observed in time to reperfusion therapy. CONCLUSIONS:
Telemedicine implementation was associated with more timely head CT
interpretation for rural patients with stroke, but no difference in early MI
care. Future work will focus on the specific manner in which telemedicine changes
ED care processes and ongoing professional education.
PMID- 29958089
TI - Determining the spiritual well-being of patients with spinal cord injury.
AB - CONTEXT/OBJECTIVE: The present study was designed to determine the spiritual
belief levels of patients with spinal cord injury as well as to examine the socio
demographic factors that affect their spiritual beliefs. DESIGN: This study was
designed as a descriptive study. SETTING: The physical therapy and rehabilitation
unit of a city Education and Research hospital. PARTICIPANTS: All patients over
the age of 18 years who have had spinal cord injuries. OUTCOME MEASURES: Data for
the study were collected using a questionnaire and the FACIT-Spiritual Well-Being
Scale. RESULTS: People with SCI in the eastern region of Turkey demonstrate
moderately high levels of spiritual well-being. A significant correlation was
identified between socio-demographic characteristics, such as age, marital
status, level of income, status of receiving care, and duration of diagnosis, and
the spiritual well-being of patients with spinal cord injury. While previous
studies have been conducted in Christian communities, the current study was the
first to be conducted in a Turkish (primarily Muslim) community. Therefore, the
current study will significantly contribute to the literature an explanation of
the spiritual well-being of patients with spinal cord injuries in Muslim
communities. CONCLUSIONS: Degree of spiritual well-being in Turkey is similar to
other regions studied to date. Spiritual well-being is important in coping with
the physical, social, economic, and emotional problems experienced by patients
after a spinal cord injury. Healthcare professionals are encouraged to support
the spiritual needs of their patients.
PMID- 29958088
TI - Individual Differences in Children's Understanding of Guilt: Links with Theory of
Mind.
AB - The author examined the relation between individual differences in children's
understanding of guilt and theory of mind (ToM) ability. Two hundred and eighteen
8- to 10-year-old children were asked to define what guilt is and report a
personal experience in which they felt this emotion. ToM was assessed with the
Reading the Mind in the Eyes Test (Children's version; Baron-Cohen et al., 2001)
and with the Strange Stories test (Happe, 1994). There were marked differences in
children's understanding of guilt even after controlling for age. Moreover, high
levels of understanding of guilt were associated with high levels of performance
on both ToM tests. The theoretical and practical implications of these results
are discussed.
PMID- 29958090
TI - ATAD2 silencing decreases VEGFA secretion through targeting has-miR-520a to
inhibit angiogenesis in colorectal cancer.
AB - ATPase family AAA domain-containing protein 2 (ATAD2) is involved in various
types of cancers, including colorectal cancer. This study aimed to determine the
role of ATAD2 in angiogenesis in colorectal cancer. Here, we downregulated ATAD2
expression in HCT116 and SW480 cells, and collected the conditioned medium (CM)
from control and ATAD2-silenced cells. The effect of CM on human umbilical vein
endothelial cells (HUVEC) was evaluated by using CCK-8, wound healing, tube
formation, Western blot, and dual-luciferase reporter assays. Our results showed
that the proliferation, migration, and tube formation of HUVEC were reduced in
presence of ATAD2-silenced CM, and the levels of phosphorylated vascular
endothelial growth factor receptor 2 (P-VEGFR2), CD31, and CD34 were
downregulated. Mechanism studies showed that ATAD2 silencing regulated the
expression of vascular endothelial growth factor A (VEGFA) and miR-520a.
Moreover, we found that miR-520a could bind to ATAD2, and its inhibitor partly
reversed the alterations in HUVEC induced by CM from ATAD2-silenced cells. In
addition, we demonstrated that miR-520a directly bound to 3'-UTR of VEGFA and
inhibited its expression. Collectively, our results indicate that ATAD2
inhibition suppresses VEGFA secretion by increasing miR-520a levels. Our study
suggests ATAD2 as a potential therapeutic target for angiogenesis in colorectal
cancer.
PMID- 29958091
TI - Horizontal transfers of LTR retrotransposons in seven species of Rosales.
AB - Horizontal transposable element transfer (HTT) events have occurred among a large
number of species and play important roles in the composition and evolution of
eukaryotic genomes. HTTs are also regarded as effective forces in promoting
genomic variation and biological innovation. In the present study, HTT events
were identified and analyzed in seven sequenced species of Rosales using
bioinformatics methods by comparing sequence conservation and Ka/Ks value of
reverse transcriptase (RT) with 20 conserved genes, estimating the dating of
HTTs, and analyzing the phylogenetic relationships. Seven HTT events involving
long terminal repeat (LTR) retrotransposons, two HTTs between Morus notabilis and
Ziziphus jujuba, and five between Malus domestica and Pyrus bretschneideri were
identified. Further analysis revealed that these LTR retrotransposons had
functional structures, and the copy insertion times were lower than the dating of
HTTs, particularly in Mn.Zj.1 and Md.Pb.3. Altogether, the results demonstrate
that LTR retrotransposons still have potential transposition activity in host
genomes. These results indicate that HTT events are another strategy for
exchanging genetic material among species and are important for the evolution of
genomes.
PMID- 29958092
TI - Self-reported healthcare utilization by adults with diabetic retinopathy in the
United States.
AB - PURPOSE: To assess healthcare utilization patterns across diabetic retinopathy
(DR) severity levels in the United States (US). DESIGN: Cross-sectional study of
699 adults, participating in the 2005-2008 National Health and Nutritional
Examination Surveys. METHODS: Diagnosis of DR was based on fundus photographs and
categorized as: (1) no DR; (2) mild/moderate nonproliferative DR (NPDR); and (3)
severe NPDR/proliferative DR (PDR). Healthcare utilization patterns were assessed
during a household questionnaire where survey participants self-reported: (1)
awareness that diabetes had affected their eyes; (2) pupil-dilation during the
past year; and (3) visits to a diabetes education/nutrition specialist during the
past year. RESULTS: Among adults with self-reported diabetes, the proportion of
those that were aware that diabetes had affected their eye was 15.3% [95%
confidence interval (C.I.)] 10.9-19.6%), 21.7% (95% C.I. 14.6-28.7%), and 81.5%
(95% C.I. 66.5-96.5%) across those with no retinopathy, mild/moderate NPDR, and
severe NPDR/PDR, respectively (p < 0.01). The utilization of a diabetic
education/nutrition specialist during the past year was 30.4% (95% C.I. 24.8
36.0%), 31.8% (95% C.I 23.4-40.2%), and 55.9% (95% C.I. 32.3-79.6%) across those
with no retinopathy, mild/moderate NPDR, and severe NPDR/PDR, respectively (p =
0.13). Pupil dilation within the past year was 62.2% (95% C.I. 56.3-68.1%), 62.1%
(95% C.I. 53.4-70.8%), and 93.8% (95% C.I. 87.3-100.0%) across those with no DR,
mild/moderate NPDR, and severe NPDR/PDR, respectively (p = 0.01). CONCLUSIONS:
Adults with diabetes in the United States, even those with the most severe forms
of DR, do not fully utilize healthcare services for diabetic eye disease. Future
studies should aim to address barriers to appropriate diabetes care.
PMID- 29958093
TI - Characterization, antimicrobial, antioxidant, and anticoagulant activities of
silver nanoparticles synthesized from Petiveria alliacea L. leaf extract.
AB - Phytosynthesis of silver nanoparticles (AgNPs) using leaf extract of Petiveria
alliacea (PA) was the focus of this research work. The PA-AgNPs were
characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy
(FTIR), transmission electron microscopy (TEM), and selected area electron
diffraction (SAED) study. Studies were made on the AgNPs for antibacterial,
antifungal, anticoagulant, free-radical scavenging, and hydrogen peroxide
scavenging activities. The crystalline PA-AgNPs were monodispersed, with a size
range of 16.70-33.74 nm and maximum absorption at 410 nm. FTIR analysis displayed
prominent peaks at 3430.6, 1711.8, and 1165.9/cm, which showed the existence of
phenolic compounds and proteins in the synthesis of AgNPs. PA-AgNPs was active
against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus, with
100% inhibition. The PA-AgNPs also displayed good antifungal properties, as the
concentrations of 100 and 150 ug/mL had 100% inhibition toward Aspergillus
fumigatus and Aspergillus flavus. However, there was 66.67% inhibition of
Aspergillus niger. It scavenged both DPPH and H2O2 by 70.69 and 89.02%,
respectively. PA-AgNPs also prevented the coagulation of human blood. This study,
being the first of its kind to use the leaf extract of PA for the synthesis of
AgNPs has shown that PA-AgNPs can find biomedical applications.
PMID- 29958094
TI - Comparative transcript profiling reveals the mechanism of female sterility
associated with seedless Ponkan mandarin (Citrus reticulata Blanco).
AB - Seedlessness is a highly desirable trait in citrus varieties. Sterility is the
key determination for seedlessness formation. However, the molecular basis for
female sterility in seedless mandarin remains unclear. Thus, a seedless Ponkan
mandarin (Citrus reticulata Blanco 'Lipeng No.2'), considered the bud mutation of
normal seedy Ponkan, was collected to identify candidate genes involved in
seedless variation. Suppression subtractive hybridization (SSH) screened 1091
uniESTs related to seedy and seedless Ponkan (727 singlets and 364 contigs),
which mainly governed catalytic activity, transferase activity, and oxygen
binding. By using RNA-Seq technology, 106 differentially expressed genes (DEGs)
were captured, of which 74 were up-regulated and 32 were down-regulated. Gene
Ontology and pathway analysis showed that six DEGs were enriched in the
biosynthesis of secondary metabolite, whereas five DEGs were enriched in the
signaling of plant hormones. The combined results of SSH and RNA-Seq indicated
the importance of amino acid metabolism in seedless Ponkan. Our findings revealed
that the mechanism of seedless Ponkan generation may be related to gene
regulation, signal cascade, and hormone levels. This study provided a solid
foundation for functional gene identification in seedless Ponkan and a good
reference for relevant research on molecular mechanisms of female sterility in
Ponkan mandarin.
PMID- 29958095
TI - Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia
reperfusion operation and in RAW264.7 macrophages treated with
lipopolysaccharide.
AB - Carnosol is a naturally occurring herbal compound, known for its antioxidative
properties. We previously found that carnosol protected mouse lungs from ischemia
reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms
underpinning carnosol-mediated lung protection, we analyzed modes of interleukin
6 (IL-6) gene expression, which is associated with lung ischemia-reperfusion
injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were
elevated in the mouse lungs subjected to clamp-reperfusion, which was associated
with elevated levels of other inflammatory modulators, such as activating
transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein
levels in mouse lung homogenates prepared after the clamp-reperfusion. On the
other hand, the ATF3 gene expression was negatively correlated with that of IL-6
in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed
by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells
were subjected to hypoxia-reoxygenation, carnosol treatment lowered oxygen
consumption after reoxygenation, which was coupled with a correlation with a
transient production of mitochondrial reactive oxygen species and following ATF3
gene expression. These results suggest that carnosol treatment could be a new
strategy for protecting lungs from ischemia-reperfusion injury by modulating the
ATF3-IL-6 axis.
PMID- 29958096
TI - Genome-wide identification of the AP2/ERF transcription factor family in pepper
(Capsicum annuum L.).
AB - The AP2/ERF family is one of the largest transcription factor families in the
plant kingdom. AP2/ERF genes contributing to various processes including plant
growth, development, and response to various stresses have been identified. In
this study, 175 putative AP2/ERF genes were identified in the latest pepper
genome database and classified into AP2, RAV, ERF, and Soloist subfamilies. Their
chromosomal localization, gene structure, conserved motif, cis-acting elements
within the promoter region, and subcellular locations were analyzed. Transient
expression of CaAP2/ERF proteins in tobacco revealed that CaAP2/ERF064,
CaAP2/ERF109, and CaAP2/ERF127 were located in the nucleus, while CaAP2/ERF171
was located in the nucleus and cytoplasm. Most of the CaAP2/ERF genes contained
cis-elements within their promoter regions that responded to various stresses
(HSE, LTR, MBS, Box-W1/W-box, and TC-rich repeats) and phytohormones (ABRE, CGTCA
motif, and TCA-element). Furthermore, RNA-seq analysis revealed that CaAP2/ERF
genes showed differential expression profiles in various tissues as well as under
biotic stresses. Moreover, qRT-PCR analysis of eight selected CaAP2/ERF genes
also showed differential expression patterns in response to infection with
Phytophthora capsici (HX-9) and in response to phytohormones (SA, MeJA, and ETH).
This study will provide basic insights for further studies of the CaAP2/ERF genes
involved in the interaction between pepper and P. capsici.
PMID- 29958097
TI - Combination of checkpoint inhibitors with other agents as a strategy to improve
anti-cancer effect - a glimpse to the future.
AB - In the last years, a remarkable progress has been made in the clinical
application of novel immunotherapy agents, the so called 'checkpoint inhibitors,'
that has revolutionized the treatment of many malignant tumors. Their design has
been based on the immune-mediated mechanisms of antitumor activity circle, such
as antigen release and presentation, activation and trafficking of T-cells into
tumors, depletion of immunosuppression, and immunogenic cell death. Various
combinations of checkpoint inhibitors are being designed and/or tested, such as
double checkpoint blockade, combination with chemotherapy, radiotherapy,
molecularly targeted agents, and other immune-directed strategies.
PMID- 29958098
TI - Pea-protein alginate encapsulation adversely affects development of clinical
signs of Citrobacter rodentium-induced colitis in mice treated with probiotics.
AB - The efficacy of two strains of Lactobacillus probiotics (Lactobacillus rhamnosus
R0011 and Lactobacillus helveticus R0052) immobilized in microcapsules composed
of pea protein isolate (PPI) and alginate microcapsules was assessed using a
mouse model of Citrobacter rodentium-induced colitis. Accordingly, 4-week-old
mice were fed diets supplemented with freeze-dried probiotics (group P),
probiotic-containing microcapsules (group PE) (lyophilized PPI-alginate
microcapsules containing probiotics), or PPI-alginate microcapsules containing no
probiotics (group E). Half of the mice (controls, groups P, PE, and E) received
C. rodentium by gavage 2 weeks after initiation of feeding. Daily monitoring of
disease symptoms (abnormal behavior, diarrhea, etc.) and body weights was
undertaken. Histopathological changes in colonic and cecal tissues, cytokine
expression levels, and pathogen and probiotic densities in feces were examined,
and the microbial communities of the distal colon mucosa were characterized by
16S rRNA sequencing. Infection with C. rodentium led to marked progression of
infectious colitis, as revealed by symptomatic and histopathological data,
changes in cytokine expression, and alteration of composition of mucosal
communities. Probiotics led to changes in most of the disease markers but did not
have a significant impact on cytokine profiles in infected animals. On the basis
of cytokine expression analyses and histopathological data, it was evident that
encapsulation materials (pea protein and calcium alginate) contributed to
inflammation and worsened a set of symptoms in the cecum. These results suggest
that even though food ingredients may be generally recognized as safe, they may
in fact contribute to the development of an inflammatory response in certain
animal disease models.
PMID- 29958099
TI - Durvalumab for the treatment of non-small cell lung cancer.
AB - INTRODUCTION: In non-small cell lung cancer (NSCLC), immunotherapy is one of
today's most important and ground-breaking systemic treatments, mainly
represented by antibodies against cytotoxic T-lymphocyte-associated protein 4
(CTLA-4) and programmed death protein 1 or ligand 1 (PD-1/PD-L1). Durvalumab
(MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1
and CD80, blocking PD-L1, but not PD-L2. Areas covered: In advanced NSCLC
patients, durvalumab has demonstrated activity and acceptable tolerability,
particularly with >=25% PD-L1 tumor expression in the EGFR and ALK wild-type
population. However, preliminary data have shown lower efficacy in EGFR mutant
and ALK-positive patients. The results from the recent PACIFIC study in locally
advanced patients have placed durvalumab as standard of care in consolidation
after chemoradiation, leading to Food and Drug Administration (FDA) approval.
Expert commentary: Early data suggest promising activity for durvalumab with the
CTLA-4 inhibitor tremelimumab, regardless of PD-L1 expression, and potentially in
combination with other drugs such as platinum-doublet chemotherapy. However,
treatment-related toxicity associated with the combinations is an important
aspect of the benefit-risk evaluation in the decision-making process. Results of
ongoing phase III trials will provide illuminating data to confirm the place of
durvalumab in the management of NSCLC patients.
PMID- 29958101
TI - Toward a Choate View of Fate.
PMID- 29958100
TI - Obstetrical and neonatal outcomes after benzodiazepine exposure during pregnancy:
Results from a prospective registry of women with psychiatric disorders.
AB - OBJECTIVE: The goal of this analysis was to examine the effect of benzodiazepine
use during pregnancy on maternal and neonatal outcomes in a cohort of women with
psychiatric disorders. METHODS: 794 evaluable women from the Massachusetts
General Hospital National Pregnancy Registry for Psychiatric Medications were
followed across pregnancy (N = 144 exposed to benzodiazepines and N = 650
unexposed). Data obtained through maternal report and medical records included
maternal outcomes (cesarean section, preeclampsia) and neonatal outcomes (birth
weight, breathing difficulty, feeding difficulty, head circumference, 5-minute
Apgar score, muscular and/or extrapyramidal symptoms, NICU admission,
prematurity). RESULTS: In adjusted analyses, infants exposed to benzodiazepines
in utero were more likely to be admitted to the NICU (OR: 2.02, 95% CI: 1.11,
3.66) and to have small head circumferences (OR: 3.89, 95% CI: 1.25, 12.03)
compared to unexposed infants. Other neonatal adverse effects such as respiratory
distress or muscular symptoms including hypotonia were not observed. There were
no significant differences in adverse obstetrical outcomes. CONCLUSIONS: Infants
exposed to benzodiazepines during pregnancy had an increased risk of NICU
admissions and small head circumferences. Confounding from psychiatric symptoms
and other variables cannot be ruled out as contributors to these findings.
PMID- 29958102
TI - Stimulating Astrocytes to Remember.
AB - Adamsky et al. show that stimulation of astrocytes potentiates synaptic
transmission and enhances behavioral performance in memory tasks. These results
demonstrate that astrocytes are actively involved in synaptic physiology and
brain function and lend further support to the idea that animal behavior results
from the coordinated activity of neurons and astrocytes.
PMID- 29958104
TI - The Walrus and the Carpenter: Complex Regulation of Tumor Immunity in Colorectal
Cancer.
AB - Immune infiltration has been correlated with survival of patients with colorectal
cancer. In this issue, Ziegler et al. reveal complex and unexpected connections
between loss of STAT3, mitophagy, and the induction of an adaptive immune
response that limits the growth of colorectal carcinoma.
PMID- 29958103
TI - Size-Dependent Segregation Controls Macrophage Phagocytosis of Antibody-Opsonized
Targets.
AB - Macrophages protect the body from damage and disease by targeting antibody
opsonized cells for phagocytosis. Though antibodies can be raised against
antigens with diverse structures, shapes, and sizes, it is unclear why some are
more effective at triggering immune responses than others. Here, we define an
antigen height threshold that regulates phagocytosis of both engineered and
cancer-specific antigens by macrophages. Using a reconstituted model of antibody
opsonized target cells, we find that phagocytosis is dramatically impaired for
antigens that position antibodies >10 nm from the target surface. Decreasing
antigen height drives segregation of antibody-bound Fc receptors from the
inhibitory phosphatase CD45 in an integrin-independent manner, triggering Fc
receptor phosphorylation and promoting phagocytosis. Our work shows that close
contact between macrophage and target is a requirement for efficient
phagocytosis, suggesting that therapeutic antibodies should target short antigens
in order to trigger Fc receptor activation through size-dependent physical
segregation.
PMID- 29958105
TI - For T Cells, the Child Is Father of the Man.
AB - When T cells respond to infectious agents, they differentiate into effector and
memory cells. In this issue of Cell, Smith et al. use a genetic "time-stamping"
method to show that the developmental time the T cell arises-near birth or as an
adult-dictates what type of T effector or memory cell results.
PMID- 29958107
TI - Lean on Me: Cell-Cell Interactions Release TGF-beta for Local Consumption Only.
AB - A new study combines detailed biochemical characterization with whole-animal
genetics and computational transcriptome data mining to reveal how the LRRC33
milieu molecule imposes an exquisite level of spatial control on TGF-beta
signaling in the CNS.
PMID- 29958108
TI - Surface Properties Determining Passage Rates of Proteins through Nuclear Pores.
AB - Nuclear pore complexes (NPCs) conduct nucleocytoplasmic transport through an FG
domain-controlled barrier. We now explore how surface-features of a mobile
species determine its NPC passage rate. Negative charges and lysines impede
passage. Hydrophobic residues, certain polar residues (Cys, His), and,
surprisingly, charged arginines have striking translocation-promoting effects.
Favorable cation-pi interactions between arginines and FG-phenylalanines may
explain this apparent paradox. Application of these principles to redesign the
surface of GFP resulted in variants that show a wide span of transit rates,
ranging from 35-fold slower than wild-type to ~500 times faster, with the latter
outpacing even naturally occurring nuclear transport receptors (NTRs). The
structure of a fast and particularly FG-specific GFPNTR variant illustrates how
NTRs can expose multiple regions for binding hydrophobic FG motifs while evading
non-specific aggregation. Finally, we document that even for NTR-mediated
transport, the surface-properties of the "passively carried" cargo can strikingly
affect the translocation rate.
PMID- 29958106
TI - CBFbeta-SMMHC Inhibition Triggers Apoptosis by Disrupting MYC Chromatin Dynamics
in Acute Myeloid Leukemia.
AB - The fusion oncoprotein CBFbeta-SMMHC, expressed in leukemia cases with chromosome
16 inversion, drives leukemia development and maintenance by altering the
activity of the transcription factor RUNX1. Here, we demonstrate that CBFbeta
SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC
expression. Upon pharmacologic inhibition of the CBFbeta-SMMHC/RUNX1 interaction,
RUNX1 shows increased binding at three MYC distal enhancers, where it represses
MYC expression by mediating the replacement of the SWI/SNF complex component BRG1
with the polycomb-repressive complex component RING1B, leading to apoptosis.
Combining the CBFbeta-SMMHC inhibitor with the BET inhibitor JQ1 eliminates
inv(16) leukemia in human cells and a mouse model. Enhancer-interaction analysis
indicated that the three enhancers are physically connected with the MYC
promoter, and genome-editing analysis demonstrated that they are functionally
implicated in deregulation of MYC expression. This study reveals a mechanism
whereby CBFbeta-SMMHC drives leukemia maintenance and suggests that inhibitors
targeting chromatin activity may prove effective in inv(16) leukemia therapy.
PMID- 29958110
TI - Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer.
PMID- 29958109
TI - The Control of Vocal Pitch in Human Laryngeal Motor Cortex.
AB - In speech, the highly flexible modulation of vocal pitch creates intonation
patterns that speakers use to convey linguistic meaning. This human ability is
unique among primates. Here, we used high-density cortical recordings directly
from the human brain to determine the encoding of vocal pitch during natural
speech. We found neural populations in bilateral dorsal laryngeal motor cortex
(dLMC) that selectively encoded produced pitch but not non-laryngeal articulatory
movements. This neural population controlled short pitch accents to express
prosodic emphasis on a word in a sentence. Other larynx cortical representations
controlling voicing and longer pitch phrase contours were found at separate
sites. dLMC sites also encoded vocal pitch during a non-speech singing task.
Finally, direct focal stimulation of dLMC evoked laryngeal movements and
involuntary vocalization, confirming its causal role in feedforward control.
Together, these results reveal the neural basis for the voluntary control of
vocal pitch in human speech. VIDEO ABSTRACT.
PMID- 29958112
TI - How Hard It Is Seeing What Is in Front of Your Eyes.
PMID- 29958111
TI - Optogenetic Editing Reveals the Hierarchical Organization of Learned Action
Sequences.
AB - The organization of action into sequences underlies complex behaviors that are
essential for organismal survival and reproduction. Despite extensive studies of
innate sequences in relation to central pattern generators, how learned action
sequences are controlled and whether they are organized as a chain or a hierarchy
remain largely unknown. By training mice to perform heterogeneous action
sequences, we demonstrate that striatal direct and indirect pathways
preferentially encode different behavioral levels of sequence structure. State
dependent closed-loop optogenetic stimulation of the striatal direct pathway can
selectively insert a single action element into the sequence without disrupting
the overall sequence length. Optogenetic manipulation of the striatal indirect
pathway completely removes the ongoing subsequence while leaving the following
subsequence to be executed with the appropriate timing and length. These results
suggest that learned action sequences are not organized in a serial but rather a
hierarchical structure that is distinctly controlled by basal ganglia pathways.
PMID- 29958114
TI - Fabrication of iron-doped titanium dioxide quantum dots/molybdenum disulfide
nanoflower for ethanol gas sensing.
AB - In this paper, a high-performance ethanol sensor based on iron (Fe)-doped
titanium dioxide (TiO2)/molybdenum disulfide (MoS2) nanocomposite was
demonstrated. Flower-like MoS2 and Fe-TiO2 quantum dots (QDs) were synthesized by
a facile hydrothermal route, and the Fe-TiO2/MoS2 composite was prepared via
layer-by-layer (LbL) self-assembly technique. The Fe-TiO2/MoS2 film sensor was
fabricated on a flame resistant (FR-4) epoxy substrate with interdigital
electrodes. The microstructure, elementary composition, and morphology of the as
prepared samples were fully characterized by X-ray diffraction (XRD), energy
dispersive spectroscopy (EDS), scanning electron microscopy (SEM), transmission
electron microscope (TEM), and X-ray photoelectron spectroscopy (XPS). The gas
sensing properties of the Fe-TiO2/MoS2 film sensor were determined at room
temperature upon exposure to different concentration of ethanol gas. The
experimental results illustrated that high response, short response/recovery
time, stable repeatability, excellent selectivity long-term stability, and a
detection limit of low ppb level was achieved by the Fe-TiO2/MoS2 sensor. The
underlying sensing mechanism of the Fe-TiO2/MoS2 sensor toward ethanol is
explored through systematically experimental investigation combining with first
principle density-functional theory (DFT) simulations. The enhanced ethanol
sensing properties were ascribed to the Fe3+ ion doping, and p-n heterojunctions
created at interfaces of n-type Fe-TiO2 and p-type MoS2.
PMID- 29958113
TI - Deaths among homeless in northern Tunisia: a 10-year study (2005-2014).
AB - OBJECTIVE: To analyze the victims profile related to death among homeless people.
STUDY DESIGN: A descriptive, retrospective, and cross-sectional study. METHODS:
We included all deaths among homeless people that occurred during a 10-year
period (2005-2014) that were autopsied in the Department of Legal Medicine of the
Charles Nicolle Hospital of Tunis. Causes of death were classified according to
the International Statistical Classification of Diseases and Related Health
Problems 10th Revision. Data were classified in three sections: sociodemographic
data, circumstances of death, and autopsy findings. A univariate data analysis
was performed. RESULTS: The sex ratio (M/F) was of 7.45. The average age was of
59 years. The majority of deaths (80.9%) occurred in the metropolis of Tunis with
a significant occurrence of cases in other governorates after the 2011 revolution
(P = 0.002). Deaths occurred more often during winter (34.8%). The bodies were
frequently discovered in public places (36.0%) and private locations (34.0%). The
deaths of 55.3% of cases were attributed to natural causes, significantly
affecting the elderly, whereas the accidental causes (25.7%) were more frequent
before the age of 49 years, followed by suicides (3.9%) and homicides (3.3%).
CONCLUSIONS: Our study highlighted a phenomenon not yet studied in Tunisia. Our
results highlight an urgent need for preventive measures focused on the
improvement of healthcare measures among homeless people.
PMID- 29958115
TI - Characterizing JUUL-related posts on Twitter.
AB - BACKGROUND: As vaping rapidly becomes more prevalent, social media data can be
harnessed to capture individuals' discussions of e-cigarette products quickly.
The JUUL vaporizer is the latest advancement in e-cigarette technology, which
delivers nicotine to the user from a device that is the size and shape of a thumb
drive. Despite JUUL's growing popularity, little research has been conducted on
JUUL. Here we utilized Twitter data to determine the public's early experiences
with JUUL describing topics of posts. METHODS: Twitter posts containing the term
"JUUL" were obtained for 1 April 2107 to 14 December 2017. Text classifiers were
used to identify topics in posts (n = 81,689). RESULTS: The most prevalent topic
wasPerson Tagging (use of @username to tag someone in a post) at 20.48% followed
by Pods (mentions of JUUL's refill cartridge) at 14.72% and Buying (mentions of
purchases) at 10.49%. The topic School (posts indicative of using JUUL or seeing
someone use JUUL while at elementary, middle, or high school) comprised 3.66% of
posts. The topic of Quit Smoking was rare at 0.29%. CONCLUSIONS: Data from social
media may be used to extend the surveillance of newly introduced vaping products.
Findings suggest Twitter users are bonding around, and inquiring about, JUUL on
social media. JUUL's discreetness may facilitate its use in places where vaping
is prohibited. Educators may be in need of training on how to identify JUUL in
the classroom. Despite JUUL's branding as a smoking alternative, very few Twitter
users mentioned smoking cessation with JUUL.
PMID- 29958116
TI - Disrupted functional connectivity within the default mode network and salience
network in unmedicated bipolar II disorder.
AB - BACKGROUND: Recent studies demonstrate that functional disruption in resting
state networks contributes to cognitive and affective symptoms of bipolar
disorder (BD), however, the functional connectivity (FC) pattern underlying BD II
depression within the default mode network (DMN), salience network (SN), and
frontoparietal network (FPN) is still not well understood. The primary aim of
this study was to explore whether the pathophysiology of BD II derived from the
pattern of FC within the DMN, SN, and FPN by using seed-based FC approach of
resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Ninety
six BD II patients and 100 HCs underwent rs-fMRI and three-dimensional structural
data acquisition. All patients were either drug naive or unmedicated for at least
6 months. The following four regions of interest were used to conduct seed-based
FC: the left posterior cingulate cortex (PCC) seed to probe the DMN, the left
subgenual anterior cingulate cortex (sgACC) and amygdala seeds to probe the SN,
the left dorsal lateral prefrontal cortex (dlPFC) seed to probe the FPN. RESULTS:
Compared with HCs, patients with BD II demonstrated hypoconnectivity of the left
PCC to the bilateral medial prefrontal cortex (mPFC) and bilateral precuneus/PCC,
and of the left sgACC to the right inferior temporal gyrus (ITG); nevertheless,
the left amygdala and dlPFC had no within-network hypo- or hyperconnectivity to
any other SN and FPN regions. CONCLUSION: Our findings suggest that disrupted FC
is located in the DMN and SN, especially in the PCC-mPFC and precuneus/PCC, and
sgACC-ITG connectivity in BD II patients.
PMID- 29958117
TI - Determinants of plasma concentrations of perfluoroalkyl and polyfluoroalkyl
substances in pregnant women from a birth cohort in Shanghai, China.
AB - Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are widely used in
commercial applications and have been commonly detected in pregnant women in
Europe and North America. However, data on PFAS concentrations in pregnant women
in China are limited. Additionally, the determinants of maternal PFAS
concentrations with respect to diet habits have been less extensively described,
especially in Asian countries. In the present study, we aimed to measure PFAS
concentrations in pregnant women and evaluate sociodemographic, lifestyle, and
dietary factors as potential determinants of PFAS concentrations. We analyzed
eleven PFASs in maternal blood samples (N = 981) collected at 12-16 weeks of
gestation between April and December 2012 at Maternal and Child Health Hospital
of Minhang District in Shanghai, China. Multivariate linear regression models
were used to examine the associations of PFAS concentrations with maternal
sociodemographic, lifestyle, and dietary factors. Eight PFASs, including
perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS),
perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic
acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA),
and perfluorotridecanoic acid (PFTrDA), were detected in >85% of the samples.
PFOA and PFOS were the predominant PFASs with high median concentrations (19.97
ng/mL and 10.81 ng/mL, respectively). Pregnant women who were older, multiparous,
well educated, passive smokers, with lower per capita household incomes, and had
lived in rooms decorated within the past two years had higher PFAS
concentrations, after mutual adjustment for maternal sociodemographic
characteristics and lifestyles. With regard to dietary factors, intake of red
meat, poultry, animal offal, fish, pastries and fried food, and drinking tap
water during pregnancy contributed to higher concentrations of most PFASs, after
adjustment for sociodemographic characteristics and lifestyles. Furthermore,
higher intake of wheat, coarse cereals, tubers, and soy products was associated
with lower maternal PFAS concentrations. Our findings indicate that PFASs were
ubiquitous among pregnant women in Shanghai. We provide new evidence for the
association between dietary factors and maternal PFAS exposure in China.
PMID- 29958118
TI - WHO/ILO work-related burden of disease and injury: Protocol for systematic
reviews of occupational exposure to dusts and/or fibres and of the effect of
occupational exposure to dusts and/or fibres on pneumoconiosis.
AB - BACKGROUND: The World Health Organization (WHO) and the International Labour
Organization (ILO) are developing a joint methodology for estimating the national
and global work-related burden of disease and injury (WHO/ILO joint methodology),
with contributions from a large network of experts. In this paper, we present the
protocol for two systematic reviews of parameters for estimating the number of
deaths and disability-adjusted life years attributable to pneumoconiosis from
occupational exposure to dusts and/or fibres, to inform the development of the
WHO/ILO joint methodology. OBJECTIVES: We aim to systematically review studies on
occupational exposure to dusts and/or fibres (Systematic Review 1) and
systematically review and meta-analyse estimates of the effect of occupational
exposure to dusts and/or fibres on pneumoconiosis (Systematic Review 2), applying
the Navigation Guide systematic review methodology as an organizing framework.
DATA SOURCES: Separately for Systematic Reviews 1 and 2, we will search
electronic academic databases for potentially relevant records from published and
unpublished studies, including Medline, EMBASE, Web of Science and CISDOC. We
will also search electronic grey literature databases, Internet search engines
and organizational websites; hand-search reference list of previous systematic
reviews and included study records; and consult additional experts. STUDY
ELIGIBILITY AND CRITERIA: We will include working-age (>=15 years) study
participants in the formal and informal economy in any WHO and/or ILO Member
State but exclude children (<15 years) and unpaid domestic workers. Eligible risk
factors will be dusts and/or fibres from: (i) asbestos; (ii) silica; and/or (iii)
coal (defined as pure coal dust and/or dust from coal mining). Included outcomes
will be (i) asbestosis; (ii) silicosis; (iii) coal worker pneumoconiosis; and
(iv) unspecified pneumoconiosis. For Systematic Review 1, we will include
quantitative prevalence studies of occupational exposure to dusts and/or fibres
(i.e. no versus any exposure) stratified by country, sex, age and industrial
sector or occupation. For Systematic Review 2, we will include randomized
controlled trials, cohort studies, case-control studies and other non-randomized
intervention studies with an estimate of any occupational exposure to dusts
and/or fibres on the prevalence of, incidence of or mortality due to
pneumoconiosis, compared with the theoretical minimum risk exposure level of no
exposure. STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors will
independently screen titles and abstracts against the eligibility criteria at a
first stage and full texts of potentially eligible records at a second stage,
followed by extraction of data from qualifying studies. At least two review
authors will assess risk of bias and the quality of evidence, using the most
suited tools currently available. For Systematic Review 2, if feasible, we will
combine relative risks using meta-analysis. We will report results using the
guidelines for accurate and transparent health estimates reporting (GATHER) for
Systematic Review 1 and the preferred reporting items for systematic reviews and
meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO REGISTRATION
NUMBER: CRD42018084131.
PMID- 29958119
TI - Tacripyrimidines, the first tacrine-dihydropyrimidine hybrids, as multi-target
directed ligands for Alzheimer's disease.
AB - Notwithstanding the combination of cholinesterase (ChE) inhibition and calcium
channel blockade within a multitarget therapeutic approach is envisaged as
potentially beneficial to confront Alzheimer's disease (AD), this strategy has
been scarcely investigated. To explore this promising line, a series of 5-amino-4
aryl-3,4,6,7,8,9-hexahydropyrimido [4,5-b]quinoline-2(1H)-thiones
(tacripyrimidines) (4a-l) were designed by juxtaposition of tacrine, a ChE
inhibitor (ChEI), and 3,4-dihydropyrimidin-2(1H)-thiones, as efficient calcium
channel blockers (CCBs). In agreement with their design, all tacripyrimidines,
except the unsubstituted parent compound and its p-methoxy derivative, acted as
moderate to potent CCBs with activities generally similar or higher than the
reference CCB drug nimodipine and were modest-to-good ChEIs. Most interestingly,
the 3'-methoxy derivative (4e) emerged as the first well balanced ChEI/CCB agent,
acting as low micromolar hChEI (3.05 MUM and 3.19 MUM on hAChE and hBuChE,
respectively) and moderate CCB (30.4% at 1 MUM) with no significant
hepatotoxicity toward HepG2 cells and good predicted oral absorption and blood
brain barrier permeability.
PMID- 29958120
TI - Comparative performance of isometric and isotonic quadriceps strength testing in
total knee arthroplasty.
AB - BACKGROUND: Early quadriceps muscle strength assessment after a total knee
arthroplasty (TKA) provides timely information on progress, but little is known
about the pain profile and predictive validity associated with common clinical
muscle strength tests. This study aimed to, in patients with a recent TKA,
examine the associations of isometric and isotonic quadriceps strength with gait
speed, accounting for knee pain experienced during testing. METHODS: A sample of
76 patients (mean age 68 years; 46 women) with a recent TKA (median, 1.5 months)
participated. Quadriceps strength was measured on both limbs using a knee
extension machine. Isotonic strength was assessed with a one-repetition maximum
test. Isometric strength was measured at 40 degrees and 70 degrees of knee
flexion using a custom-built load cell. To allow for valid comparisons between
the tests, quadriceps strength symmetry ratios were calculated. Knee pain during
testing was measured using an 11-point pain scale. Fast gait speed was measured
using the 10-m walk test. RESULTS: Compared with isotonic test, quadriceps
strength ratio was higher for the 40 degrees flexion isometric test (P = 0.01),
and this difference may be explained by the lower knee pain intensity elicited
during the isometric tests (P's < 0.001). All strength measures were closely
associated with fast gait speed after adjustment for knee pain and covariates
(P's < 0.001). CONCLUSIONS: Early in the post-TKA period, isometric and isotonic
strength tests may be used to assess quadriceps strength but these tests are not
interchangeable. Isometric quadriceps testing may be preferable to isotonic
testing as it was associated with lower knee pain intensity.
PMID- 29958121
TI - Visualization and analysis of mapping knowledge domain of road safety studies.
AB - Mapping knowledge domain (MKD) is an important application of visualization
technology in Bibliometrics, which has been extensively applied in psychology,
medicine, and information science. In this paper we conduct a systematic analysis
of the development trend on road safety studies based on the Science Citation
Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) articles
published between 2000 and 2018 using the MKD software tools VOSviewer and Sci2
Tool. Based on our analysis, we first present the annual numbers of articles,
origin countries, main research organizations and groups as well as the source
journals on road safety studies. We then report the collaborations among the main
research organizations and groups using co-authorship analysis. Furthermore, we
adopt the document co-citation analysis, keywords co-occurrence analysis, and
burst detection analysis to visually explore the knowledge bases, topic
distribution, research fronts and research trends on road safety studies. The
proposed approach based on the visualized analysis of MKD can be used to
establish a reference information and research basis for the application and
development of methods in the domain of road safety studies. In particular, our
results show that the knowledge bases (classical documents) of road safety
studies in the last two decades have focused on five major areas of "Crash
Frequency Data Analysis", "Driver Behavior Questionnaire", "Safety in Numbers for
Walkers and Bicyclists", "Road Traffic Injury and Prevention", and "Driving Speed
and Road Crashes". Among the research topics, the five dominant clusters are
"Causation and Injury Severity Analysis of Road Accidents", "Epidemiologic Study
and Prevention of Road Traffic Injury", "Intelligent Transportation System and
Active Safety", "Young drivers' driving behavior and psychology", and "Older
drivers' psychological and physiological characteristics". Finally, the burst
keywords in research trends include Cycling, Intelligent Transportation Systems,
and Distraction.
PMID- 29958122
TI - Can the post-error effect mask age-related differences in congruency conditions
when education and overall accuracy are controlled for?
AB - OBJECTIVE: Age-related differences in stimulus-response congruency tasks have
been attributed to older adults' greater difficulties in handling the irrelevant
spatial-dimensional overlap between stimulus and response. However, performance
on congruency tasks may also be influenced by the previous trial accuracy (i.e.
post-error effect), which may affect young and older adults differently. The main
objective of this study was to analyse age-related differences in the post-error
effect as a function of congruency. In addition, we examined the meditational
role of the Gratton effect on the age-related differences in the post-error
slowing (PES) and post-error increased accuracy (PIA) as a function of
congruency. METHOD: The sample comprised 165 healthy adult participants with
diverse educational attainment, divided into five age groups. Participants
performed a spatial stimulus-response congruency task. Age-related differences in
the post-error effect were analysed for each congruency condition taking into
account educational attainment and overall accuracy. Statistical procedures were
used to neutralize age-related processing speed effects on the PES. RESULTS: PES
was observed across all age groups, except the Very old group (aged 85-98 years),
and it was not related to congruency condition. PIA was observed across age
groups in all congruency conditions and was slightly higher in incongruent
trials. Evidence of simultaneous PES and PIA was found for young participants and
older participants under 85 years. The Very old group did not need to
significantly slow down their responses after errors to improve accuracy. No age-
related difference was found in the influence of the Gratton effect on PES or PIA
as a function of congruency. CONCLUSIONS: PES and PIA were observed in young
adults and older adults under 85 years old. Evidence of simultaneous PES and PIA
in the young and older age group (except for the Very old) indicates that the
post-error effect can be interpreted in terms of recruitment of additional
resources to prevent subsequent errors. Slightly higher accuracy was observed in
the incongruent condition in post-error trials relative to pre-error correct
trials across age groups.
PMID- 29958123
TI - Increased CYFRA 21-1, CEA and NSE are Prognostic of Poor Outcome for Locally
Advanced Squamous Cell Carcinoma in Lung: A Nomogram and Recursive Partitioning
Risk Stratification Analysis.
AB - OBJECTIVES: This study aimed to: (1) assess the prognostic significance of serum
tumor markers in locally advanced squamous cell carcinoma in lung (LA-SCCL); (2)
generate a nomogram to predict the overall survival (OS) and (3) identify a
prognostic stratification to assist the therapeutic decision-making. METHODS: LA
SCCL patients receiving definitive radiotherapy and baseline tumor marker
measurement were eligible for this retrospective study. Cox proportional hazards
regression was used to determine independent factors associated with various
survival indexes and a nomogram was created to estimate the 5-year OS probability
for individual patient. The identified prognostic factors were recruited into a
recursive partitioning analysis (RPA) for OS to stratify patients with distinct
outcome. RESULTS: A total of 224 patients were eligible for analysis. Increased
cytokeratin-19 fragment (CYFRA 21-1) was independently associated with inferior
OS, progression free survival (PFS) and a borderline decreased local-regional
progression free survival (LRPFS). Elevated carcino-embryonic antigen (CEA)
served as an unfavorable determinant for OS and increased neuron-specific enolase
(NSE) was predictive of poor distant metastasis free survival (DMFS). A nomogram
integrating KPS, TNM stage, CEA and CYFRA 21-1 was created, resulting in a c
index of 0.62. RPA identified 4 prognostic classifications, with median OS of
27.6, 19.9, 17.3 and 10.9 months for low, intermediate, high and very-high risk
groups, respectively. CONCLUSIONS: Baseline tumor marker panel including CYFRA 21
1, CEA and NSE can be prognostic of outcome for LA-SCCL receiving definitive
radiotherapy. The RPA identified four prognostic subgroups, which could assist
personalized therapy and clinical trial design in LA-SCCL.
PMID- 29958124
TI - At all hospitals in the State of Iowa over a decade, the number of cases
performed during weekends or holidays increased approximately proportionally to
the total caseload.
AB - STUDY OBJECTIVE: We tested the hypothesis that over many years - a decade -
hospitals' proportions of surgical cases that were performed on weekends and
holidays remained stable. DESIGN: Retrospective cohort study. SETTING: Iowa
Hospital Association data were from January 1, 2007, through June 30, 2017. The N
= 42 hospitals included were those with at least 10 cases performed during
holidays or weekends for each of the periods. MEASUREMENTS: The number of
surgical cases performed at each hospital during each of the 21 half-year periods
was considered the count of unique combinations of hospital, patient, and date
with at least one major therapeutic procedure. MAIN RESULTS: Absolute predictive
errors in cases per weekend or holiday day were calculated using a proportional
model and using a quadratic model for each hospital and half-year period. Pooling
among hospitals, the sample mean absolute predictive errors were greater for the
proportional model than for the quadratic model (P < 0.0001). However, the mean
difference was just 0.0027 cases per weekend or holiday day (SE 0.0001),
significantly less than even 1 case per day (P < 0.0001). The sample means of the
pairwise differences in predictive errors were smaller than 1 case per day for
all 42 hospitals, significantly so for 41 of the 42 hospitals (P <= 0.005). These
conditions applied to all other hospitals in the state, because each performed
few cases on weekends and holidays. CONCLUSIONS: For the anesthesia group caring
for patients at a hospital over several years, weekend and holiday anesthesia
caseload should be expected to increase approximately proportionately to changes
during regular workdays. Average weekend workload can be benchmarked using
hospitals' percentages of operating room cases performed on weekends and
holidays.
PMID- 29958125
TI - Perioperative dexmedetomidine reduces delirium after cardiac surgery: A meta
analysis of randomized controlled trials.
AB - STUDY OBJECTIVE: To evaluate the efficiency of dexmedetomidine on the incidence
of delirium in patients after cardiac surgery. DESIGN: Meta-analysis of
randomized controlled trials. SETTING: Operating room and Intensive Care Unit
(ICU). PATIENTS: Ten trials with a total of 1387 patients undergoing cardiac
surgery met the inclusion criteria. INTERVENTION: Randomized controlled trials
(RCTs) comparing the effect of dexmedetomidine versus non-treatment of
dexmedetomidine (normal saline (NS), propofol and other anesthetic drugs) on
delirium in patients undergoing cardiac surgery were retrieved from
PubMed/Medline, Embase, the Cochrane Library and Web of science. The primary
outcome was the incidence of delirium. The secondary outcomes were the rate of
bradycardia and hypotension, the duration of mechanical ventilation and the
length of ICU and hospital stay. MAIN RESULTS: Compared with the control group,
Dexmedetomidine significantly decreased the incidence of postoperative delirium,
(risk ratio 0.46; 95% confidence intervals, 0.34 to 0.62; P < 0.00001), while the
incidence of bradycardia was increased in dexmedetomidine group (risk ratio 1.86;
95% confidence intervals, 1.16 to 2.99; P = 0.01). There was no significant
difference between groups with regarding to the occurrence of hypotension (risk
ratio 0.90; 95% confidence intervals, 0.59 to 1.38; P = 0.63), the duration of
mechanical ventilation (Mean Difference 0.21; 95% confidence intervals, -0.70 to
1.12; P = 0.65), and the length of ICU (Standard Mean Difference - 0.07; 95%
confidence intervals, -0.19 to 0.06; P = 0.3) and hospital stay (Mean Difference
0.13; 95% confidence intervals, -0.56 to 0.30; P = 0.56). CONCLUSION:
Perioperative dexmedetomidine administration decreased the incidence of delirium
in patients after cardiac surgery, but might increase the rate of bradycardia.
Furthermore, we did not observe significant differences in the incidence of
hypotension, the duration of mechanical ventilation and length of ICU and
hospital stay between groups. Future studies are needed to ascertain the effect
of dexmedetomidine on the incidence of delirium after coronary artery bypass
grafting (CABG) and in patient with cognitive disorder at baseline, whether
intraoperative dexmedetomidine infusion could reduce postoperative delirium and
the optimal dose of dexmedetomidine.
PMID- 29958126
TI - A triclosan turn-ON fluorescence sensor based on thiol-capped core/shell quantum
dots.
AB - Triclosan (TCS) is a common antimicrobial found in many personal care products. A
large amount of TCS thus enters the wastewater system leading to the accumulation
thereof in water sources. In this work, core-shell structured GSH-CdSe/ZnS
fluorescent quantum dots (QDs) were synthesized based on organometallic synthesis
with a thiol ligand capping agent. The GSH-CdSe/ZnS QDs showed excellent
photostability and a photoluminescence quantum yield of 89%. The fluorescence of
the GSH-CdSe/ZnS QDs was enhanced by the introduction of TCS, likely owing to
fluorescence resonance energy transfer from TCS to the QDs, allowing for its use
as a "turn on" fluorescence probe for the detection and determination of TCS. A
linear response was observed in the range of 10-300 nmol L-1 with limits of
detection and quantification of 3.7 and 12.4 nmol L-1 respectively. The probe
displayed good recoveries (94%-117.5%) for the determination of TCS in tap and
river water samples which demonstrated the suitability of this novel sensor for a
monitoring application of environmental relevance.
PMID- 29958127
TI - Individualized texting for adherence building (iTAB) for methamphetamine users
living with HIV: A pilot randomized clinical trial.
AB - BACKGROUND: Methamphetamine (METH) use poses a barrier to antiretroviral therapy
(ART) adherence. We evaluated the efficacy of the individualized texting for
adherence building (iTAB) intervention among persons living with HIV (PLWH) who
meet criteria for METH use disorder. We examined daily associations between ART
adherence and text-reported METH use and depressed mood. METHODS: We conducted a
single site, 2-arm, 6-week, pilot randomized clinical trial comparing a
personalized, bidirectional, text messaging system (iTAB; n = 50) to an active
control condition (n = 25). All participants received adherence psychoeducation
and daily texts assessing METH use and depressed mood. The iTAB group received
personalized daily ART reminder texts. ART adherence was monitored using
Medication Event Monitoring System (MEMS) caps. RESULTS: Response rates to daily
ART reminder texts were high (79%), with good concordance between MEMS-derived
and text-reported ART adherence (p < .001). Intervention groups did not differ in
MEMS-derived ART adherence (68% iTAB, 70% active control; p = .68); however,
participants in the iTAB group had fewer METH use days (median 14.4 iTAB, 22.0
active control; p = .05). Text-reported METH use, but not depressed mood, was
associated with poorer MEMS-derived ART adherence. CONCLUSIONS: High text
response rates and good concordance between MEMS-derived and text-reported
adherence suggests text messaging is a feasible intervention delivery approach
that provides a valid indication of ART adherence. Reductions in METH use among
iTAB participants suggest daily health reminders may help attenuate substance
use. Further research is needed to substantiate daily text messaging as a harm
reduction approach.
PMID- 29958129
TI - "There was no love there": Intergenerational HIV disclosure, and late
presentation for antiretroviral therapy in Northern Malawi.
AB - Despite access to antiretroviral testing and treatment, high rates of mortality
among HIV infected infants and young children persist, often because they are
diagnosed too late to benefit from treatment. Most research assumes that
treatment delays are a proxy indicator for ongoing HIV-related stigma. My
argument is different. Instead I argue that secrecy and truth-telling are
socially produced; that is I consider how gendered and intergenerational dynamics
regulate how and to whom secrets should be shared. In this article I draw on two
years of ethnographic fieldwork (2008-2010) in Northern Malawi with 35 HIV
positive children, their primary caregivers, as well as multiple interviews with
their extended therapy networks [N = 96] and community stakeholders [N = 72] to
examine how social hierarchies influenced the timing of an HIV diagnosis for
infected infants. My findings indicate that it is neither necessary nor
strategically advantageous for some women to disclose their HIV status to their
husbands. Rather, grandparents play pivotal roles at facilitating HIV disclosure
between intimate partners, which in turn leads to timely HIV diagnoses for
infected children. This article contributes to a body of literature that
questions the usefulness of the concept of "stigma" for understanding late
presentation for ART among infants and children.
PMID- 29958128
TI - Tapering off and returning to buprenorphine maintenance in a primary care Office
Based Addiction Treatment (OBAT) program.
AB - BACKGROUND: Guidelines recommend long-term treatment for opioid use disorder
including the use of buprenorphine; however, many patients desire to eventually
taper off. This study examines the prevalence and patient characteristics of
patients that voluntarily taper off buprenorphine. METHODS: This is a 12-year
retrospective cohort study of adults on buprenorphine in a large urban safety-net
primary care practice. The primary outcome was completion of a voluntary
buprenorphine taper, which was further characterized as a medically supervised or
unsupervised taper. The secondary outcome was re-engagement in care after taper.
Descriptive statistics and estimated proportions of both taper completion and re
engagement in treatment were calculated using Kaplan-Meier estimates. RESULTS:
The study sample included 1308 patients with a median follow-up time of 316 days;
48 patients were observed to taper off buprenorphine during the study period,
with an estimated proportion of 15% (95%CI: 10%-21%) based on Kaplan Meier
analyses. Less than half of the tapers, 45.8% (22/48), were medically supervised.
Thirteen of the 48 patients subsequently, re-engaged in buprenorphine treatment
(estimated proportion 61%, 95%CI: 27%-96%), based on Kaplan-Meier analyses with
median follow-up time of 490 days. DISCUSSION: Despite the fact that many
patients desire to discontinue buprenorphine, a minority had a documented taper.
Among those who tapered, more than half did so unsupervised by the clinic and a
majority of those who tapered off returned to buprenorphine treatment within two
years. As many patients are unable to successfully taper off buprenorphine, the
medical community must work to address any barriers to long-term maintenance.
PMID- 29958130
TI - Loneliness as a mediator of the relationship between shame and health problems in
young people exposed to childhood violence.
AB - RATIONALE: Shame related to childhood violence can be detrimental to mental and
physical health. Shame may erode social bonds. OBJECTIVE: In this study we tested
whether loneliness is an important pathway between violence-related shame and
health problems. METHOD: Individuals who reported exposure to childhood violence
in a telephone interview survey in 2013 (wave one) were re-contacted 12-18 months
later (wave two), as part of a more general survey of the Norwegian adult
population. In total, 505 adolescent and young adult participants (mean age = 21
years) responded to questions about violence exposure, violence-related shame,
loneliness, anxiety/depression symptoms, and somatic health complaints. We used
counterfactually based causal mediation analysis within the structural equation
modelling framework to test whether loneliness mediated a potential association
between shame and health. RESULTS: Shame had a profound effect on
anxiety/depression symptoms and we identified both direct and indirect effects.
Loneliness mediated about one third of the relationship between shame and
anxiety/depression symptoms. The relationship between shame and somatic health
complaints was weaker in total, but this more modest effect largely occurred
indirectly through loneliness. CONCLUSIONS: Our results add to the literature by
highlighting the role of loneliness in the relationship between shame and health.
Shame may have the potential to break down social connectedness, with a
detrimental effect on health. Clinicians may find it helpful to pay close
attention to the way shame regulates social interaction. Preventing social
isolation and loneliness may promote good health in violence victims.
PMID- 29958131
TI - Carbon nitride/titania nanotubes composite for photocatalytic degradation of
organics in water and sludge: Pre-treatment of sludge, anaerobic digestion and
biogas production.
AB - In this study, carbon nitride/titania nanotubes (C3N4/TiO2 NTs) composites were
synthesized for the enhanced visible light mediated photocatalytic degradation
and pre-treatment of wastewater sludge for enhanced biogas production. The co
existence of C3N4 and TiO2 NTs and visible light activity was confirmed by XRD,
TEM, UV-visible and PL spectroscopy. The photocatalytic performance of TiO2 NTs
with 2% of melamine (precursor of C3N4), enhanced the degradation of 2
chlorophenol (2-CP) (k = 0.0176 min-1), where 96.6% removal was achieved at
optimum pH 7.0 and 2-CP concentration of 30 mg/L. On the other hand, the
application of C3N4/TiO2 NTs for solubilization of the rigid structure of sludge
by photocatalysis released the soluble organics showing an improvement in sCOD
production (4587 mg/L). Subsequently, anaerobic digestion of solubilized sludge
has improved the methane production (723.4 ml kg-1 VS) by 1.37 and 1.6 times
compared to that in anaerobic digestion with photolytic and raw sludge, thus
showing a promising applicability for biogas production from sludge and
wastewater treatment.
PMID- 29958132
TI - The role of technical protocols and partnership engagement in developing a
decision support framework for fisheries management.
AB - In the context of the Common Fisheries Policy Reform, the implementation of
multiannual management plans for fisheries and the annual quota negotiations
between EU member states has generated a growing demand from stakeholders and
managers for integrated advice that goes beyond the usual biological advice. This
has led to the emergence of bio-economic tools and methods for the comparison of
the biological, economic and social tradeoffs associated with alternative options
for fisheries management. A Decision Support Framework (DSF) has been developed
in this context, with the objective to tackle technical and methodological
challenges to be able to provide bio-economic advices to support decision at
national and European level. It is based on a partnership approach involving the
fishing industry, managers and scientists and on technical protocols. We present
the development of a partnership DSF within three local case studies,
highlighting key challenges and lessons learnt regarding appropriateness and
application of a DSF. The data processing methods and collaborative platform were
pivotal for scoping out objectives and management options, and for aligning DSF
outcomes with decision makers' needs and agendas. Definition of common standards
and institutionalization of the use of partnership DSF are still required to
operationalize the integrated advice process at national and European levels.
PMID- 29958133
TI - Optimization and modeling of methyl orange adsorption onto polyaniline nano
adsorbent through response surface methodology and differential evolution
embedded neural network.
AB - Presence of pigments and dyes in water bodies are growing tremendously and pose
as toxic materials and have severe health effects on human and aquatic creatures.
Treatments methods for removal of these toxic dyes along with other pollutants
are growing in different dimensions, among which adsorption was found a cheaper
and efficient method. In this study, the performance of polyaniline-based nano
adsorbent for removal of methyl orange (MO) dye from wastewater in a batch
adsorption process is studied. Along with this to minimize the number of
experiments and obtain optimal conditions, a multivariate predictive model based
on response surface methodology (RSM) is developed. This is compared with data
driven modeling using the artificial neural network (ANN) which is integrated
with differential evolution optimization (DEO) for prediction of the adsorption
of MO. The interactive effects on MO removal efficiency with respect to
independent process variables were investigated. The fit of the predictive model
was found to good enough with R2 = 0.8635. The optimal ANN architecture with 5-12
1 topology resulted in higher R2 and lower RMSE of 0.9475 and 0.1294
respectively. Pearson's Chi-square measure which provides a good measurement
scale for weighing the goodness of fit is found to be 0.005 and 0.038 for RSM and
ANN-DEO respectively, and other statistical metrics evaluated in this study
further confirms that the ANN-DEO is very superior over RSM for model
predictions.
PMID- 29958134
TI - l-arginine alters the proteome of frozen-thawed bovine sperm during in vitro
capacitation.
AB - The aim of this work was to evaluate the proteomic changes that occurred in the
frozen-thawed bovine spermatozoa after the addition of l-arginine (L-arg) during
in vitro sperm capacitation. Aspects related to the sperm capacitation pattern
like membrane integrity, mitochondrial activity, sperm motility and vigor, and
the sperm proteome were determined. These were respectively assessed by
chlortetracycline staining, H342/PI, JC-1, light microscopy, and the proteomic
abundance by nUPLC-MS/MS analysis. Frozen-thawed sperm from three Nellore bulls
were capacitated in vitro for 3 h in sp-TALP medium supplemented with 20 MUg/mL
heparin (Control) or with 20 MUg/mL heparin plus 1 mM L-arg (L-arg group). Data
were subjected to analysis of variance and means compared by SNK test at 5%
probability. When compared to Control, the percentage of sperm motility was
higher in the L-arg group (P < 0.05). For test data after 3 h of incubation,
sperm capacitated with L-arg showed higher membrane integrity and mitochondrial
potential when compared to Control (P < 0.05). Moreover, we observed an increase
in the percentage of capacitated sperm pattern (P < 0.05). Protein abundance
analysis identified 367 proteins. Forty proteins were differentially abundant
between Control and L-arg group (P < 0.05), of which 11 were up-regulated, and 29
were down-regulated in L-arg group. In addition, we observed that one protein was
uniquely abundant in the L-arg group. Our findings indicate that the addition of
L-arg to the culture medium presented a differential protein abundance pattern
and increased the bovine frozen-thawed sperm quality and the percentage of
capacitated sperm. The proteomic changes observed may be linked to the molecular
mechanisms involved in the action of L-arg on the in vitro sperm capacitation of
cattle.
PMID- 29958135
TI - Engaging mothers with substance use issues and their children in early
intervention: Understanding use of service and outcomes.
AB - Mothers who use substances need integrated, multi-sectoral intervention services
to support substance use discontinuation. We explored mothers' service use at
Breaking the Cycle, an early intervention and prevention program for pregnant and
parenting women and their young children in Toronto, Canada. We conducted
retrospective analyses of families' service records and client charts (N = 160).
Aims were to 1) describe women's use of service, 2) examine how early engagement
of pregnant women related to postnatal service use, and 3) examine the
circumstances in which women ended their service relationship with Breaking the
Cycle. Specifically, we examined circumstances at service ending relating to
women's service goals; custody status with children; and global substance-use,
parent-child relationship, and child development outcomes. We found that these
vulnerable women were actively engaged in many services and for a long duration,
early engagement was associated with greater service use, and greater service use
was associated with more positive circumstances upon ending service. Results
provide support for a relational approach to service that promotes not only the
relationship between mother and child, and mother and service provider, but also
highlights relationships among staff, between staff and management, and between
community partners as integral to effective service delivery. Integrating
positive relationships at all levels is critical to support vulnerable families
with complex needs.
PMID- 29958136
TI - Who are the smokers who never plan to quit and what do they think about the risks
of using tobacco products?
AB - INTRODUCTION: Smoking cigarettes is the most harmful way to use tobacco. Smokers
who do not plan to quit present a particular challenge in reducing the morbidity
and mortality from tobacco use. Switching to a lower harm product might encourage
them to end their use of combusted cigarettes. This study aimed to better
understand smokers who do not intend to quit (including their demographic and
worldviews as indicators of their social, cultural, and political dispositions)
and their perceived risks of cigarettes and possible lower-risk products such as
e-cigarettes. METHODS: Participants were 2572 current smokers. Data were pooled
from 2015 and 2016 cross-sectional surveys of national probability samples of
U.S. adults and analyzed with multivariable logistic regressions. RESULTS:
Smokers who never plan to quit comprise 14.3% of current U.S. smokers and are
more likely to be older (24.2% among 65+ years old vs. 9.8% among 18-24) and less
likely to have ever used e-cigarettes. A one-unit increase in hierarchical
worldview (measured on a 1-6 scale) was associated with a 20% increase in the
odds of never planning to quit. Those who denied that cigarettes cause disease or
death (aORs between 1.6 and 2.0) or were uncertain (aORs: 2.5-2.7) were more
likely to never plan to quit compared to those who agreed. They did not view
risks of e-cigarettes substantially different compared to smokers who plan to
quit. CONCLUSION: One in seven U.S. smokers never plans to quit and might benefit
from interventions which reflect their hierarchical worldviews and increase their
risk perceptions of combustible cigarettes.
PMID- 29958138
TI - Registered nurses' preferences for rural and urban jobs: A discrete choice
experiment.
AB - BACKGROUND: Recruitment and retention of nurses is an ongoing challenge for
employers in rural areas worldwide. There is limited information available
regarding influences on nurses' job choice in the U.S. and little understanding
of how nurses make trade-offs between desired and less desirable job
characteristics when choosing between jobs. OBJECTIVES: The purpose of this
research was to examine the hospital job preferences of registered nurses in the
U.S. The specific objectives of the study were: 1) To identify the relative
importance of key job attributes on registered nurse job choice, and 2) To
predict the impact of changes in the levels of attributes on the probability of
registered nurses choosing one job over another. DESIGN AND SETTING: A discrete
choice experiment was developed and applied in the U.S. using California as a
study site. PARTICIPANTS: 190 registered nurses currently working in nursing or
intending to return to work in nursing from urban, large-, small- and isolated
rural communities. METHODS: The survey instrument was developed through a
literature review and semi-structured interviews with nurse experts, utilizing a
hypothetical job in a hospital medical / surgical unit. Experimental design
principles were applied to create a discrete choice experiment which was pilot
tested with urban and rural nurses. The survey was mailed to a random sample of
1000 licensed registered nurses in California. A mixed logit model was used to
estimate nurses' preferences for different levels of the job attributes.
Willingness to pay estimates and simulations of job uptake rates were calculated.
RESULTS: Eight factors were identified as important to job choice: earnings,
nursing voice in management, tuition reimbursement, scheduling, patient care
team, leadership, location and nursing sensitive patient care outcomes.
Respondents valued a cohesive patient care team (coefficient 1.95, [SE 0.23]) and
a strong nursing voice in management (coefficient 1.56, [SE 0.22]) highest. A job
in a large urban inland location was negatively valued (coefficient -0.69, [SE
0.25]). Around 72% of respondents chose to stay in their current job when this
choice was offered. While earnings were important, nurses were willing to
sacrifice earnings to secure other valued job characteristics when choosing
between jobs. CONCLUSIONS: Study findings provide information on how job
characteristics are valued by nurses in California. Findings suggest job seekers
may be 65-75 percent more likely to choose a job when valued job characteristics
are present. Our findings are particularly relevant to rural hospitals with
limited financial resources.
PMID- 29958137
TI - Cooperation Between Pten and Smad4 in Murine Salivary Gland Tumor Formation and
Progression.
AB - Salivary gland tumor (SGT) is a rare tumor type, which exhibits broad-spectrum
phenotypic, biological, and clinical heterogeneity. Currently, the molecular
mechanisms that cause SGT pathogenesis remain poorly understood. A lack of animal
models that faithfully recapitulate the naturally occurring process of human SGTs
has hampered research progress on this field. In this report, we developed an
inducible keratin 5-driven conditional knockout mouse model to delete gene(s) of
interest in murine salivary gland upon local RU486 delivery. We have deleted two
major tumor suppressors, Pten, a negative regulator of the PI3K pathway, and
Smad4, the central signaling mediator of TGFbeta pathway, in the murine salivary
gland. Our results have shown that deletion of either Pten or Smad4 in murine
salivary gland resulted in pleomorphic adenomas, the most common tumor in human
SGT patients. Deletion of both Pten and Smad4 in murine salivary gland developed
several malignancies, with salivary adenoid cystic carcinoma (SACC) being the
most frequently seen. Molecular characterization showed that SACC exhibited mTOR
activation and TGFbeta1 overexpression. Examination of human SGT clinical samples
revealed that loss of Pten and Smad4 is common in human SACC samples,
particularly in the most aggressive solid form, and is correlated with survival
of SACC patients, highlighting the human relevance of the murine models. In
summary, our results offer significant insight into synergistic role of Pten and
Smad4 in SGT, providing a rationale for targeting mTOR and/or TGFbeta signaling
to control SGT formation and progression.
PMID- 29958139
TI - Long noncoding RNA HOXD-AS1 promotes non-small cell lung cancer migration and
invasion through regulating miR-133b/MMP9 axis.
AB - HOXD antisense growth associated long noncoding RNA (HOXD-AS1) was reported to be
dysregulated and exert crucial roles in tumorigenesis and progression of multiple
malignancies. However, the role and mechanism of action of HOXD-AS1 in the
carcinogenesis and progression of non-small lung cell cancers (NSCLC) remains
largely unknown. HOXD-AS1, miR-133a and Matrix metallopeptidase 9 (MMP-9) mRNA
expression were detected by quantitative real-time polymerase chain reaction
assays in NSCLC tissues and cell lines. Cell counting kit-8, wound healing and
transwell invasion assays were performed to evaluate cell proliferation,
migration and invasion abilities, respectively. Luciferase assays were used to
investigate binding seeds between miR-133b and HOXD-AS1. Western blot assay were
performed to detect protein expression. Here higher expression of HOXD-AS1 was
found in NSCLC tumor tissues compared with normal lung tissues, and was
associated with lymph node metastasis, high tumor node metastasis (TNM) stage,
and poor overall survival rate of patients with NSCLC. Knockdown of HOXD-AS1
significantly inhibited proliferation, migration and invasion of NSCLC cells.
Additionally, we found that miR-133b was a direct downstream target of HOXD-AS1
in NSCLC. miR-133b inhibition reverse the inhibitory effect of HOXD-AS1 knockdown
on the proliferation, migration, and invasion of NSCLC cells. Furthermore, HOXD
AS1 positively regulated the expression of MMP-9 (a target of miR-133b) in NSCLC
cells. These results suggest that HOXD-AS1 might be a potential prognostic
biomarker and a novel therapeutic target for treating NSCLC.
PMID- 29958140
TI - Endometriosis: Perspective, lights, and shadows of etiology.
AB - Endometriosis refers to the growth of ectopic endometrial tissue outside the
uterine cavity. About 10-15% of female in reproductive age suffer from
endometriosis. Several etiologies - such as oxidative stress, inflammatory
factors and cytokines, genetic etiology, and hormone role - have been reported
for endometriosis. Indeed, oxidative stress leads to abnormalities by the
production of ROS and RNS. The mechanism of endometriosis genesis is a
complicated process that concerns the alterations in cellular immunity. Also,
endometriosis is a hormonal response that illustrates stimulation in steroid
hormone production. Genetic polymolymorphisms and epigenetic factors are also
important in endometriosis initiation and progression. This review paper presents
the role of oxidative stress, reactive oxygen species (ROS), and antioxidants and
inflammatory, genetic, and epigenetic factors involved in the initiation and
progression of the endometriosis.
PMID- 29958141
TI - Oridonin enhances the cytotoxicity of 5-FU in renal carcinoma cells by inducting
necroptotic death.
AB - BACKGROUND: 5-fluorouracil (5-FU) is widely used for the treatment of renal
carcinoma. However, drug resistance remains the reason for failure of
chemotherapy. Oridonin, extracted from Chinese herb medicine, displays anti-tumor
effect in several types of cancer. Whether oridonin could enhance the effect of 5
FU in renal carcinoma has not been studied. METHODS: 786-O cells were used in the
current study. Cell death was measured by MTT assay or live- and dead-cell
staining assay. Glutathione (GSH) level was examined by ELISA. Necroptosis was
identified by protein levels of receptors interaction protein-1 (RIP-1) and RIP
3, lactate dehydrogenase (LDH) and high mobility group box-1 protein (HMGB1)
release, and poly [ADP-ribose] polymerase-1 (Parp-1) activity. Using a xenograft
assay in nude mice, we tested the anti-tumor effects of the oridonin combined
with 5-FU. RESULTS: 5-FU only induced apoptosis in 786-O cells. Oridonin
activated both apoptosis and necroptosis in 786-O cells. Oridonin-induced
necroptosis was reversed by addition of GSH or its precursorN-acetylcysteine
(NAC). Oridonin-induced necroptosis was associated by activated JNK, p38, and ERK
in 786-O cells, which were abolished by GSH or NAC treatment. However, JNK, p38,
and ERK inhibitors showed no effect on oridonin induced-cell death. GSH or NAC
treatment partly abolished the synergistic effects of oridonin and 5-FU on cell
death. Oridonin enhanced the cytotoxicity of 5-FU both in vitro and in vivo.
CONCLUSION: Oridonin enhances the cytotoxicity of 5-FU in renal cancer cells
partially through inducing necroptosis, providing evidence of using necroptosis
inducers in combination with chemotherapeutic agents for cancer treatment.
PMID- 29958142
TI - Lavatera critica controls systemic insulin resistance by ameliorating adipose
tissue inflammation and oxidative stress using bioactive compounds identified by
GC-MS.
AB - BACKGROUND: Lavatera critica, a leafy green herb, is reported to have many
pharmacological activities; but, the improvement of insulin sensitivity against
the high gram-fat diet (HGFD)-caused insulin resistance (IR) has not yet been
studied. OBJECTIVE: This study evaluated the role of Lavatera critica leaf
extract (LCE) in systemic insulin resistance through the alleviation of adipose
tissue inflammation and oxidative damage in HGFD fed mice. METHODS: The mice were
fed with HGFD for 10 weeks and the diet was supplemented with LCE each day for
the next five weeks. Body weight, food intake, leptin, blood glucose, insulin,
insulin resistance, and pro- and anti-inflammatory genes expression were assessed
on day 106. RESULTS: The HGFD control mice displayed markedly elevated adipose
tissue inflammation, oxidative stress, insulin inactivity, and hyperglycemia.
Administration of LCE in the HGFD mice, especially a dose of 100 mg/kg, lowered
the body weight, food intake, plasma leptin, plasma glucose, plasma insulin,
insulin resistance, and increased the food efficacy ratio when compared with the
HGFD control mice. The oral glucose tolerance test (OGTT) revealed that LCE
prevented further increase in the circulating levels after the glucose load. LCE
treated mice demonstrated a marked suppression of pro-inflammatory cytokines mRNA
expression. On the other hand, the mice showed a higher anti-inflammatory genes
mRNA expression in the adipose tissue. In addition, LCE treatment improved the
oxidative damage as evidenced by the reduced levels of lipid hydroperoxides and
thiobarbituric acid reactive substances coupled with the increased antioxidants
(superoxide dismutase, total glutathione, glutathione/glutathione disulfide ratio
and glutathione peroxidase) in the adipose tissue, plasma and erythrocytes. Gas
chromatography-mass spectrometry analysis of the bioactive compounds revealed the
presence of 9, 12, 15-octadecatrienoic acid, vitamin E, phytol, hexadecanoic
acid, benzenepropanoic acid, and stigmasterol. CONCLUSIONS: These findings prove
that LCE improves the insulin-sensitizing activity in the mouse model of HGFD
caused IR, probably due to the amelioration of adipose tissue inflammation and
oxidative damage. Hence, the LCE could serve as a useful anti-diabetic agent.
PMID- 29958143
TI - Aucubin protects against lipopolysaccharide-induced acute pulmonary injury
through regulating Nrf2 and AMPK pathways.
AB - Aucubin (Ai), a natural compound isolated from plants, including Aucuba japonica
and Eucommia ulmoides, shows significant anti-inflammatory and anti-oxidative
bioactivities. Here, we attempted to explore the protect effects of Ai on LPS
induced acute lung injury (ALI). Our results indicated that Ai increased the
survival rate and ameliorated pathogenic processes in lipopolysaccharide (LPS)
induced mice. However, nuclear factor erythroid 2-related factor 2 (Nrf2)
deletion may impede protective effect of Ai. Additionally, Ai reduced oxidative
stress by down-regulating malondialdehyde (MDA) and O2. activity, and enhancing
Nrf2-targeted signals, including heme oxygenase-1 (HO-1) and quinone
oxidoreductase-1 (NQO-1). Also, Ai inhibited pro-inflammatory cytokines and
phosphorylated-nuclear factor-kappaB (NF-kappaB) expression in LPS-administrated
mice. However, these protective effects of Ai were suppressed in Nrf2-knockout
mice. Importantly, Nrf2-deficiency showed no effects on phosphorylated AMP
activated protein kinase (p-AMPK) expression in mice treated with LPS and Ai.
Similarly, in LPS-induced macrophages, Ai reduced reactive oxygen species (ROS)
generation, elevated NQO-1 and HO-1 expression. LPS-stimulated pro-inflammatory
cytokines and p-NF-kappaB were reversed by Ai. Of note, we found that Ai-induced
Nrf2 activation was dependent on AMPK activation. Suppression of AMPK levels may
inhibit Nrf2 activation, finally leading to up regulation of inflammatory
response and oxidative stress. Thus, our findings indicated the crosstalk between
Nrf2 and AMPK signaling pathways, and the interaction was essential for the anti
oxidant and anti-inflammatory effects of Ai in LPS-induced macrophages, which
might be beneficial for finding new treatments against ALI.
PMID- 29958144
TI - Lower extremity muscle activity during descent from varying step heights.
AB - During step descent, lower extremity musculature is critical for positioning the
foot and ankle for initial contact and stabilizing the structures following
contact. Although continuous stair descent has been extensively examined,
curb/single transition steps where many injuries occur requires further study.
The purpose of this study was to identify the influence of landing strategy and
step height on lower extremity muscle activity of uninjured individuals during
transition step descent. Twenty-two participants walked along a level walkway,
stepped down a single step (heights: 5-cm, 15-cm, 25-cm) landed with the heel or
forefoot, and continued walking. Muscle activity of the leading leg's peroneals,
tibialis anterior, and medial gastrocnemius were recorded 200 ms before and after
initial contact. Two-way Repeated Measures ANOVAs within the three step heights
and two landing strategies were run for both the pre- and post-contact periods.
Step height by landing strategy interactions existed during the pre-contact
periods for all three muscles. During the post-contact period, all muscle
activity increased with each step height increment. Additionally, the medial
gastrocnemius and tibialis anterior demonstrated significant landing strategy
differences. This study highlights the importance of considering both landing
strategy and step height when designing or interpreting investigations of
transition step negotiation.
PMID- 29958145
TI - The structure of mentors' behaviour in clinical nursing education: Confirmatory
factor analysis.
AB - AIMS: To study if a three-factor structure of mentors' behaviour identified
through exploratory factor analysis could be confirmed in a dataset assessing
mentors' performance using structural equation modelling. BACKGROUND: To measure
mentor's behaviour in clinical nursing education in China, a specific instrument
was developed and preliminarily validated; a three-factor structure (professional
development, facilitating learning and psychosocial support) was identified in a
dataset of assessment of the importance of mentors' each behaviour using
exploratory factor analysis and Mokken scale analysis. DESIGN: A cross-sectional
study with online and hard copy survey was applied. METHODS: Convenience sampling
was conducted. Nursing students (n = 634) in Southwest China participated in the
study from July to August 2014. Confirmatory factor analysis was used. RESULTS:
Mentors' behaviour can be perceived as a secondary order factor with three first
order factors: professional development; facilitating learning; and psychosocial
support. CONCLUSION: The three-factor structure of mentors' behaviour was
confirmed by structural equation modelling. This structure is visible in mentors'
real performance and implies that this instrument could be used to assess
mentors' behaviour in addition to students' expectation from mentors.
PMID- 29958146
TI - The self over time.
AB - People often have difficulty making decisions that maximize well-being over time,
and researchers have explored various reasons for why such poor 'intertemporal'
decision-making may arise. In this article, I review a body of work that has
focused on how the relationship between current and future selves may influence
judgments and decisions. Namely, I spotlight research suggesting that the future
self is often thought of as another person and how feelings about this 'other'
person impact decisions across domains. I then review two insights gleaned from
this research: in order to positively modify long-term decision-making,
interventions may wish to focus on (1) strengthening the felt bond between
current and future selves, or (2) reducing the subjective pain of sacrifices made
by the current self. I close with several questions future research may wish to
address.
PMID- 29958147
TI - Drugs for treatment for alcohol use disorders expose to interactions with others
... for little benefit if any.
PMID- 29958148
TI - Potential of using sodium bicarbonate as external carbon source to cultivate
microalga in non-sterile condition.
AB - In this study, a saline-alkaline tolerant microalgal strain was isolated and
identified as Chlorella sp. LPF. This strain was able to grow at pH values up to
10 and at salinities up to 5%, and tolerated to 80 g L-1 of sodium bicarbonate.
The utilization of bicarbonate as carbon source significantly promoted microalgal
growth and lipid production. In the non-sterile cultivation supplying with 80 g L
1 of sodium bicarbonate, the microalgal growth had no difference with their
growth in the sterile medium; however, the bacterial growth was suppressed and
the cell number decreased to low levels after six days cultivation. This study
gives an insight into the potential that using high concentration of sodium
bicarbonate as external carbon source to cultivate microalga in non-sterile
condition, and suggests a possibility of using bicarbonate as growth promoter and
antibacterial agent for the microalgal outdoor cultivation.
PMID- 29958149
TI - Effect of pretreatments on corn stalk chemical properties for biogas production
purposes.
AB - Different pretreatments were evaluated on corn stalk (Zea mays) applied as a
lignocellulosic source in anaerobic co-digestion with swine manure, using
sulfuric acid (H2SO4) and hydrogen peroxide (H2O2) for biogas production
purposes. Using H2SO4 we achieved a 75.1% removal of the hemicellulose fraction,
in low acid concentrations (0.75% v.v-1). However, this technique inhibited the
co-digestion process. Pretreatment with 12% of H2O2 (pH 11.5) increased the
cellulose fraction by 73.4% and reduced the lignin content by 71.6%. This
pretreatment is recommended for biogas production, as it increased the final
volume of biogas by 22% and reduced the digestion time by one third. So, a
promising alternative was obtained in order to facilitate the anaerobic digestion
of the carbohydrates present in this biomass.
PMID- 29958150
TI - Small molecules as tools to study the chemical epigenetics of lysine acetylation.
AB - Lysine acetylation has emerged as a key post-translational modification found at
many sites throughout the cell. It plays an important role in epigenetic
processes, and more generally in the regulation of protein stability and
interactions. Acetyl groups are installed by lysine acetyltransferases and
removed by lysine deacetylases. Acetylated lysine residues function as binding
sites for bromodomains, which are epigenetic reader protein modules that mediate
protein-protein interactions. Progress in the development of small molecules that
interfere with lysine acetylation has stimulated intensive research activity in
diverse therapeutic areas. Some of these compounds are already marketed as drugs
or are undergoing clinical trials. Here we review recent progress in the
development of small molecules that interfere with lysine acetylation state and
acetyl-lysine reading by bromodomains.
PMID- 29958151
TI - Assessment of potentially inappropriate medications in elderly according to Beers
2015 and STOPP criteria and their association with treatment satisfaction.
AB - OBJECTIVE: To assess and compare, according to Beers and STOPP criteria, the
frequency and causes of potentially inappropriate medications (PIMs) in elderly,
as well as the relationship between PIMs use and patient's treatment
satisfaction, evaluated using the Treatment Satisfaction Questionnaire for
Medications (TSQM). METHOD: 350 patients (mean age = 73.49 years), taking a total
of 1893 medications, were enrolled from community pharmacies. RESULTS: 6.2% and
20.4% of the medications were inappropriate according to the STOPP and Beers
lists respectively; 103 (29.4%) and 210 (60%) patients had at least one PIM
according to STOPP and Beers criteria respectively. The most common cause of PIM
was a full dose of proton pomp inhibitor for >8 weeks (STOPP) and using a drug
that exacerbates/causes syndrome of inappropriate antidiuretic hormone secretion
(Beers). The number of medications taken by the participant, advanced age, female
gender, prescription of medications for anxiety/depression,
ulcers/gastroesophageal reflux, rheumatoid arthritis and epilepsy significantly
increased the PIMs number. When using STOPP criteria, all TSQM subscale scores
were significantly lower among patients with PIM use compared to those without
PIM. The same trend was observed for Beers critertia, with a significant
difference reached for side effects and convenience subscales only. CONCLUSION:
Selecting the appropriate tools to assess PIMs, prescribers and patient education
regarding the risks associated with PIMs, and patient's perception and
satisfaction regarding his treatment, are critical issues to be addressed among
older adults.
PMID- 29958152
TI - A paradigm of endothelium-protective and stent-free anti-restenotic therapy using
biomimetic nanoclusters.
AB - Drug-eluting stents are the most commonly employed method to control post
angioplasty restenosis. Unfortunately, they exacerbate life-threatening stent
thrombosis because of endothelium damage caused by both drug and stenting. To
solve this major medical problem, an endothelium-protective and stent-free anti
restenotic method is highly desirable. Here we have generated a biomimetic
intravenous delivery system using dendritic polymer-based nanoclusters, which
were coated with platelet membranes for targeting to the injured arterial wall
where restenosis occurs. These nanoclusters were loaded with an endothelium
protective epigenetic inhibitor (JQ1) or an endothelium-toxic status quo drug
(rapamycin), and compared for their ability to mitigate restenosis without
hindering the process of re-endothelialization. Fluorescence imaging of Cy5
tagged biomimetic nanoclusters indicated their robust homing to injured, but not
uninjured arteries. Two weeks after angioplasty, compared to no-drug control,
both rapamycin- and JQ1-loaded biomimetic nanoclusters substantially reduced (by
>60%) neointimal hyperplasia, the primary cause of restenosis. However, whereas
the rapamycin formulation impaired the endothelial re-coverage of the denuded
inner arterial wall, the JQ1 formulation preserved endothelial recovery. In
summary, we have created an endothelium-protective anti-restenotic system with
biomimetic nanoclusters containing an epigenetic inhibitor. This system warrants
further development for a non-thrombogenic and stent-free method for clinical
applications.
PMID- 29958153
TI - The effect of immunization against gonadotropin-releasing factor on growth
performance, carcass characteristics and boar taint relevant to pig producers and
the pork packing industry: A meta-analysis.
AB - Meta-analysis was used to compare pigs immunocastrated (IC) with Improvac(r)
versus physically castrated (PC) or entire male (EM) pigs. Performance and
carcass data as most relevant for producers and packers were analyzed and the
risk of boar taint was assessed by comparing the number of pigs exceeding the
consumer thresholds of detection (ToD) for skatole and androstenone. A total of
78 articles fulfilled pre-defined inclusion criteria. Compared to PC pigs, IC
pigs have a higher average daily gain (ADG; +32.54 g/day, P < 0.0001) and more
favorable feed conversion ratio (FCR; -0.234 kg/kg, P < 0.0001), higher live
weight and percentage lean, and lower hot carcass weight (HCW) and dressing
percentage. Compared to EM pigs, IC pigs have a higher ADG (+65.04 g/day, P <
0.0001), FCR (+0.075 kg/kg, P < 0.0001), live weight and HCW, and a similar
dressing percentage. Conventionally raised IC pigs yield more valuable meat
compared to PC (+0.628 kg) and EM (+1.385 kg) pigs. Heavy IC pigs (HCW > 97.7 kg)
destined for the production of high-quality cured products gain approximately 0.3
kg more ham than their PC counterparts, with backfat and intramuscular fat still
fulfilling the requirements for high-quality cured products. The risk of
exceeding the ToD for skatole and androstenone is similar in IC and PC pigs, but
significantly higher in EM pigs. Results from our meta-analyses confirm growth
performance advantages of IC pigs compared with PC or EM pigs, and reveal a
higher gain of valuable meat and a similar risk of boar taint as estimated for PC
pigs.
PMID- 29958154
TI - Silver nanoparticles: Their role as antibacterial agent against Aeromonas
salmonicida subsp. salmonicida in rainbow trout (Oncorhynchus mykiss).
AB - The rise of bacterial resistance to antibiotics is one of the great challenges of
our age. One of the strategies to limit the development of antibiotics resistance
is the investigation of alternative antimicrobials. As silver nanoparticles
demonstrated a potent bactericidal activity in vitro, the aim of this study was
to evaluate the in vivo antibacterial activity of silver nanoparticles against
Aeromonas salmonicida subsp. salmonicida. Rainbow trout (n = 120) were divided
into four groups of 30 fish each. First group was challenged with A. salmonicida
(Positive control), the second group was challenged with A. salmonicida and
exposed to silver nanoparticles by immersion for three hours (100 MUg/L), the
third group was challenged with A. salmonicida and intraperitoneally injected
with silver nanoparticles (17 MUg/mL) and the fourth group was sham-treated and
served as a negative control group. At the 7th day post challenge, histopathology
of the positive control group revealed the presence of bacterial aggregates in
tissues with degenerative and necrotic changes, while at the 35th day post
challenge, only liver necrosis persisted. Silver nanoparticles-treated and
negative control groups did not show any clinical signs, mortalities or
histopathological alterations and they were tested negative for A. salmonicida.
The immersion in silver nanoparticles did not result in detectable residues of
silver in the muscles 35 days after treatment. These findings demonstrate the
antibacterial properties of silver nanoparticles against A. salmonicida
infection. Therefore, they could be used for development of antibacterial agents
in aquaculture.
PMID- 29958155
TI - Purification, crystallization and preliminary X-ray crystallographic studies of
swine MHC class I complexed with an FMDV CTL epitope Hu64.
AB - Up to now, no crystal structure of swine leukocyte antigen 2 (SLA-2) molecules
was reported. In order to elucidate the structure of SLA-2 and to study the
cytotoxic T lymphocyte (CTL) epitopes derived from foot-and-mouth disease virus
(FMDV), a complex of swine major histocompatibility complex (MHC) class I
molecule (SLA-2 haplotype, Hebao allele) with swine beta2-microglobulin and the
CTL epitope FMDV-Hu64 (ALLRTATYY) derived from O serotype of FMDV VP1 protein
(residues 64-72) was refolded and crystallized. The crystal, which belonged to
space group P212121, diffracted to 2.5 A resolution and had unit cell parameters
a = 48.37, b = 97.75, c = 166.163 A. These results will help to determine the
first structure of a SLA-2 molecule in the context of an FMDV CTL epitope.
PMID- 29958156
TI - Effect of the housing system (free-range vs. open air cages) on growth
performance, carcass and meat quality and antioxidant capacity of rabbits.
AB - Growth performances and meat quality of free-range or cage raised rabbits were
compared in 36 male animals. Rabbits were raised in free-range areas (2000
cm2/head) or in open-air cages (800 cm2/head) from weaning to 99 days old. Daily
weight gain and final live weight were higher (P < 0.05) for the rabbits raised
in cages which presented a more favourable feed conversion ratio (P < 0.05) than
in the free-range group. The average feed intake, liver and empty gastro
intestinal tract weights were higher (P < 0.05) in the free-range group, while
the interscapular fat percentage was higher (P < 0.05) in the caged rabbits.
Loins of free-range rabbits had higher amount of PUFA n-6 in neutral lipids (P <
0.05) whereas their polar lipids were richer in PUFA n-6 and n-3 than in those of
the cage group. Muscular fat of free-raised rabbits was found to be less
susceptible to be oxidized, having a higher antioxidant capacity than the caged
group.
PMID- 29958157
TI - Multi-parametric MR imaging using apparent diffusion coefficient and fat fraction
in quantification of bone marrow in pediatrics with Gaucher disease.
AB - PURPOSE: To assess multi-parametric MR imaging with apparent diffusion
coefficient (ADC) and fat fraction (FF) in detection and quantification of bone
marrow involvement in pediatric patients with Gaucher disease. MATERIAL AND
METHODS: This study was conducted upon 29 pediatric patients with Gaucher disease
and 13 age and sex matched controls that underwent diffusion-weighted MR imaging
and dual-echo gradient recalled echo imaging. The ADC and FF of the bone marrow
were calculated. RESULTS: There was significant difference in ADC (P = 0.001) and
FF (P = 0.001) of bone marrow between patients and controls. The cutoff ADC and
FF differentiate patients from controls were 0.47 * 10-3 mm2/s and 0.36 with area
under the curve of 0.947 and 0.885 and accuracy of 86.5% and 83.8% respectively.
There was significant difference in ADC (P = 0.001) and FF (P = 0.001) between
untreated (n = 17) and treated (n = 12) patients. The cutoff ADC and FF
differentiate untreated from treated patients were 0.39 * 10-3 mm2/s and 0.27
with area under curve of 0.886 and 0.851 and accuracy of 88% and 84%
respectively. CONCLUSION: Multi-parametric MR imaging using ADC and FF are
quantitative imaging parameters that can be used for detection and quantification
of vertebral bone marrow involvement in pediatric patients with Gaucher disease.
PMID- 29958158
TI - Diagnosing extensor carpi ulnaris tendon dislocation with dynamic rotation MRI of
the wrist.
AB - OBJECTIVE: The purpose of this study was to retrospectively correlate the
kinematic dynamic rotation MRI (DR-MRI) of the wrist for assessment of extensor
carpi ulnaris (ECU) tendon subluxation and dislocation. MATERIAL AND METHODS: The
presence of an ECU tendon subluxation or dislocation on the DR-MRI report was
correlated to findings of the surgical report. RESULTS: DR-MRI findings showed an
ECU subluxation in 12 cases and an ECU dislocation in 13 cases. Surgery showed an
ECU subluxation in 13 cases and an ECU dislocation in 12 cases (K = 0.92).
CONCLUSION: DR-MRI is a feasible method to visualize ECU tendon subluxation and
dislocation.
PMID- 29958159
TI - How does patellar tendon advancement alter the knee extensor mechanism in
children treated for crouch gait?
AB - BACKGROUND: The patellar tendon advancement (PTA) procedure, often coupled with a
distal femoral extension osteotomy (DFEO), is increasingly used to treat
persistent crouch gait. In this study, we investigated relationships between
patella position, knee flexion, and the patellar tendon moment arm in children
treated with the DFEO and PTA procedures. METHODS: We retrospectively analyzed
pre- and post-operative radiographs and gait metrics from 63 knees that underwent
DFEO and PTA procedures at Gillette Children's Specialty Healthcare. A
computational musculoskeletal model of the knee was used to simulate the PTA
procedure and predict the effects on the patellar tendon moment arm. RESULTS:
Approximately 80% of the knees exhibited patella alta prior to surgery. Post
operatively, 86% of the knees exhibited patella baja. The surgically altered
patella position produced a 13% increase in the patellar tendon moment arm in
extended knee postures, which agreed well with model predictions. However, the
computational model also suggests that baja may compromise patellar tendon moment
arms in flexed knee postures. Crouch gait was significantly reduced
postoperatively, with a 27 +/- 18 degrees reduction in average knee flexion in
stance. There was considerable inter-subject variability in outcomes with nine
knees not exhibiting a meaningful enhancement of knee extension (<15 degrees
change). The subjects who improved were significantly younger and exhibited
greater enhancement of the patellar tendon moment arm after surgery. CONCLUSIONS:
This study shows that the PTA procedure enhances the lever arm of the knee
extensor mechanism, and this factor may be important in resolving crouch gait.
PMID- 29958160
TI - Cellular interactions of functionalized superparamagnetic iron oxide
nanoparticles on oligodendrocytes without detrimental side effects: Cell death
induction, oxidative stress and inflammation.
AB - Iron oxide nanoparticles have the capability to cross Blood Brain Barrier (BBB)
and hence are widely investigated for biomedical operations in the central
nervous system. Before being used for the biomedical purpose, it is necessary to
investigate its biocompatibility, dosimetry and biological interaction. In the
present study, in-house synthesized superparamagnetic iron oxide nanoparticles
(SPIONs) were functionalized using the polymer, PolyEthylene Glycol (PEG) and a
fluorophore (Rhodamine). The interaction of these nanoparticles with murine
oligodendrocytes 158N was studied using different assays. The nanoparticles were
taken up by the cells via endocytosis and there was a dose-dependent increase in
the intracellular iron content as revealed by flow cytometry, transmission
electron microscopy and confocal microscopy. Nanoparticles remained stable inside
cells even after 24 h. Cell sorting capacity using a magnet depended on the
number of particles interact per cell. SPIONs exhibited good biocompatibility as
no toxicological responses, including morphological changes, loss of viability,
oxidative stress or inflammatory response (IL-1beta, IL-6 secretion) were
observed. Together, these data show that the in-house synthesized SPIONs have no
side effects on 158N cells, and constitute interesting tools for biomedical
applications across brain, including cellular imaging and targeting.
PMID- 29958161
TI - Exposure to perfluoroalkyl substances and associations with serum thyroid
hormones in a remote population of Alaska Natives.
AB - Perfluoroalkyl substances (PFASs) are known to accumulate in traditional food
animals of the Arctic, and arctic indigenous peoples may be exposed via
consumption of subsistence-harvested animals. PFASs are suspected of disrupting
thyroid hormone homeostasis in humans. The aim of this study is to assess the
relationship between serum PFASs and thyroid function in a remote population of
Alaska Natives. Serum samples were collected from 85 individuals from St.
Lawrence Island, Alaska. The concentrations of 13 PFASs, as well as free and
total thyroxine (T4), free and total triiodothyronine (T3), and thyrotropin (TSH)
were quantified in serum samples. The relationships between circulating
concentrations of PFASs and thyroid hormones were assessed using multiple linear
regression fit with generalized estimating equations. Several PFASs, including
perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), were positively
associated with TSH concentrations when modeled individually. PFOS and PFNA were
significantly associated with free T3 and PFNA was significantly associated with
total T3 in models with PFAS*sex interactive terms; these associations suggested
negative associations in men and positive associations in women. PFASs were not
significantly associated with concentrations of free or total T4. Serum PFASs are
associated with circulating thyroid hormone concentrations in a remote population
of Alaska Natives. The effects of PFAS exposure on thyroid hormone homeostasis
may differ between sexes.
PMID- 29958162
TI - Physiological, ultrastructural and proteomic responses of tobacco seedlings
exposed to silver nanoparticles and silver nitrate.
AB - Since silver nanoparticles (AgNPs) are a dominant nanomaterial in consumer
products, there is growing concern about their impact on the environment.
Although numerous studies on the effects of AgNPs on living organisms have been
conducted, the interaction of AgNPs with plants has not been fully clarified. To
reveal the plant mechanisms activated after exposure to AgNPs and to
differentiate between effects specific to nanoparticles and ionic silver, we
investigated the physiological, ultrastructural and proteomic changes in
seedlings of tobacco (Nicotiana tabacum) exposed to commercial AgNPs and ionic
silver (AgNO3) from the seed stage. A higher Ag content was measured in seedlings
exposed to AgNPs than in those exposed to the same concentration of AgNO3.
However, the results on oxidative stress parameters obtained revealed that, in
general, higher toxicity was recorded in AgNO3-treated seedlings than in those
exposed to nanosilver. Ultrastructural analysis of root cells confirmed the
presence of silver in the form of nanoparticles, which may explain the lower
toxicity of AgNPs. However, the ultrastructural changes of chloroplasts as well
as proteomic study showed that both AgNPs and AgNO3 can affect photosynthesis.
Moreover, the majority of the proteins involved in the primary metabolism were up
regulated after both types of treatments, indicating that enhanced energy
production, which can be used to reinforce defensive mechanisms, enables plants
to cope with silver-induced toxicity.
PMID- 29958163
TI - The mobility and plant uptake of gallium and indium, two emerging contaminants
associated with electronic waste and other sources.
AB - Gallium (Ga) and indium (In) are increasingly susceptible to soil contamination
via disposal of electronic equipment. Chemically similar to aluminium (Al), these
elements may be mobile and bioavailable under acidic conditions. We sought to
determine extent and nature of Ga and In mobility in the soil - plant system and
thus their potential to enter the food chain. Batch sorption experiments on a
high fertility silt loam (pH 5.95, CEC 22 meq 100 g-1) showed strong retention of
both elements to the soil matrix, with mean distribution coefficient (KD) values
of 408 and 2021 L kg-1 for Ga and In respectively. KD increased with
concentration, which we attributed to precipitation of excess ions as insoluble
hydroxides. KD decreased with increased pH as Ga/In(OH)2+ and Ga/In(OH)2+
transitioned to Ga/In(OH)4-. Movement into the aboveground portions of perennial
ryegrass (Lolium perenne L.) was low, with bioaccumulation factors of 0.0037 for
Ga and 0.0002 for In; foliar concentrations peaked at 11.6 mg kg-1 and 0.015 mg
kg-1 respectively. The mobility of Ga and In in the soil - plant system is low
compared to other common trace element contaminants such as cadmium, copper, and
zinc. Therefore, Ga and In are likely to accumulate in soils and soil ingestion,
either directly, via inhaled dust, or dust attached to food, will be the largest
pathway into the food chain. Future work should focus on the effect of redox
conditions on Ga and In, as well as uptake into acidophilic plants such as
Camellia spp., which accumulate Al.
PMID- 29958166
TI - Social determinants of environmental health: A case of sanitation in rural
Jharkhand.
AB - An estimated 56% of households in rural India defecated in the open in 2015,
making India the most significant contributor to the global sanitation burden.
This cross-sectional study uses data collected in 2016 from 499 households in
rural Jharkhand to understand the constraints of latrine adoption and drivers of
sanitation preferences (plans to adopt toilets and willingness to pay for
toilets). Focusing on a region with a large tribal population, the study examines
two types of predictors, namely structural factors (objective socioeconomic,
sociocultural and ecological characteristics) and psychosocial drivers (perceived
unaffordability of toilet, hygiene and sanitation knowledge, perceived health
risks, attitudes, both descriptive and injunctive social norms, and perceived
water stress). We find that structural constraints related to educational,
economic and sociocultural inequalities predict toilet ownership. Low sanitation
rates can neither be attributed to a lack of expressed demand nor lack of
recognition of the disadvantages of open defecation. Similarly, variations in
sanitation preferences are neither explained by differences in hygiene and
sanitation knowledge nor by understandings of sanitation health risks. We find
that perceived unaffordability, attitudes (perceived benefits of toilet and
disadvantages of OD) and perceived descriptive social norms are of key
importance. This implies a potential for persuasive strategies that manipulate
social norms around sanitation, particularly if they simultaneously address
perceptions around financial unaffordability of toilets and around the benefits
of toilets. Importantly, however, attempts to change sanitation preferences by
acting on forces of social (dis)approval (i.e. through perceived injunctive
social norms) may be ineffective and generate negative unintended consequences.
PMID- 29958165
TI - Sorption of cationic organic substances onto synthetic oxides: Evaluation of
sorbent parameters as possible predictors.
AB - Knowledge on the sorption behavior of cationic organic substances in aquatic
systems is vital for their risk assessment due to the increasing detection of
such chemicals in the hydrosphere. Their sorption behavior is strongly influenced
by sorption processes onto mineral surfaces (e.g., oxides, clays). To contribute
to the development of prediction tools, the impact of sorbent characteristics on
the sorption strength was studied in a highly-idealized model system. In addition
to the properties of the solid phase, the concentration of other ions in direct
competition for sorption sites and the molecular structure of the sorbate were
changed to separate ion exchange and non-ion exchange processes. The study
includes in total 120 systematic column experiments using five extensively
characterized synthetic oxides (three silica gels, two aluminum oxides), three
probe molecules (two structurally related cationic substances, one neutral
compound), and four distinctively different NaCl concentrations. The results show
that the concentration of OH groups on the sorbent surface is a meaningful
descriptor for the observed variations in sorption capacity onto different
oxides. Compound-specific linear correlations were obtained, enabling the
prediction of sorption coefficients. In addition, a more complex sorption
behavior of organic cations compared to uncharged molecules were observed as
demonstrated by the sorption results at different electrolyte concentrations.
Thus, the study provides an important step towards a better principal mechanistic
understanding of organic cation sorption. However, further work using other
sorbents including natural ones and other probe molecules is needed to verify the
identified relationships within the scope of developing reliable prediction
models for cation sorption.
PMID- 29958164
TI - Ultrasound enhanced electrochemical oxidation of Alizarin Red S on boron doped
diamond(BDD) anode:Effect of degradation process parameters.
AB - Textile wastewater is characterized by high toxicity, complex structure, and
resistance to biodegradation. Therefore, advanced oxidation technologies have
received extensive attention. However, it is usually difficult to achieve a
desired degradation effect using a single technology. The combination of various
advanced oxidation technologies is an important way to achieve efficient
degradation of organic wastewater. The present investigation was focused on
ultrasound enhanced electrochemical oxidation (US-EO) of typical anthracene
Alizarin Red S dye on a boron doped diamond anode. Our work indicates that
ultrasonic oxidation technology which is mainly based on cavitation, can produce
strongly oxidizing active substances such as OH, HO2, O, and H2O2, that
accelerate the destruction of the dye molecular structure and achieve dye
decolorization and mineralization. The effects on cavitation and decomposition of
ARS by the parameters that affect degradation, including solution temperature,
initial pH, and electrolytes, were examined. Results show that low temperature
was more conducive to ultrasonic cavitation in the US-EO process; the degradation
efficiency rate of EO was higher than that of US-EO when the solution temperature
was above 45 degrees C. Ultrasonic cavitation was significantly more efficient
in acid than in alkaline conditions. Almost 100% color removal and 86.07% COD
removal was achieved for 100 mg L-1 ARS concentration with a 0.05 M Na2SO4
electrolyte, temperature of 30 degrees C and pH of 4.97 after 3 h. GC-MS
analysis showed that the intermediate products of ARS in the US-EO process were
phthalic anhydride, PEAs and bisphenol A, which is eventually mineralized to CO2
and H2O.
PMID- 29958167
TI - Effects of nanoplastics on Mytilus galloprovincialis after individual and
combined exposure with carbamazepine.
AB - Plastic pollution is a worldwide problem, highlighted by the fact that plastic
materials degrade into nano-size particles (<100 nm), potentially becoming more
bioavailable as well as a source of entry of other contaminants into organisms.
The present study aimed to assess the effects of polystyrene nanoplastics (PS),
individually or combined with carbamazepine (Cbz), on the Mediterranean mussel,
Mytilus galloprovincialis. For this purpose, mussels were exposed for 96 h to a
concentration range of PS (from 0.05 up to 50 mg L-1), to Cbz (6.3 MUg L-1) alone
and to the mixture of PS + Cbz (0.05 mg L-1+ 6.3 MUg L-1). Molecular and
biochemical biomarkers were assessed in the digestive glands, gills and
haemolymph. The abundance of mRNA in the digestive glands and gills revealed
significant alterations in the expression of genes associated with
biotransformation, DNA repair, cell stress-response and innate immunity. Combined
exposure of PS + Cbz induced significant downregulation in gene expression (e.g.,
hsp70) when compared to individual exposure. Total oxidant status increased in
digestive glands after exposure to 0.5 mg L-1 PS. Moreover, increased total
antioxidant capacity and esterase activity were observed for PS 50 mg L-1, in
digestive glands and gills, respectively. The PS induced effects on
neurotransmission, measured as inhibition of cholinesterase activity in
haemolymph. Genotoxicity was found in haemocytes after exposure to PS, Cbz and
their mixture. Moreover, lipid peroxidation was observed for 0.05 mg L-1 PS
exposure, showing that nanoplastics can induce oxidative damage. The present
study demonstrated that PS, even at low concentrations, led to alterations on the
assessed mussels' endpoints.
PMID- 29958168
TI - Riverine dissolved organic carbon in Rukarara River Watershed, Rwanda.
AB - Dissolved organic carbon (DOC) loading is rarely estimated in tropical
watersheds. This study quantifies DOC loading in the Rukarara River Watershed
(RRW), a Rwandan tropical forest and agricultural watershed, and evaluates its
relationship with hydrological factors, land use and land cover (LULC), and
topography to better understand the impact of stream DOC export on watershed
carbon budgets. The annual average load for the study period was 977.80 kg C,
which represents approximately 8.44% of the net primary productivity of the
watershed. The mean daily exports were 0.37, 0.14, 0.075 and 0.32 kg C/m2 in
streams located in natural forest, tea plantation, small farming areas, and at
the outlet of the river, respectively. LULC is a factor that influences DOC
loading. The quick flow was the main source of stream DOC at all study sites.
Stream DOC increases with increasing water flow, indicating a positive
relationship. Thus, the expectation is that a change in land cover and/or
rainfall will result in a change of stream DOC dynamics within the watershed.
Topography was also found to influence the dynamics of stream DOC through its
effect on overland flow in terms of drainage area and total length of flow paths.
Tea plantations were located in areas of high drainage density and projected
increase of rainfall in the region, as a consequence of climate change, could
increase stream DOC content and affect stream water quality, biodiversity,
balance between autotrophy and heterotrophy, and bioavailability of toxic
compounds within the RRW.
PMID- 29958169
TI - The effect of municipal treated wastewater on the water holding properties of a
clayey, calcareous soil.
AB - Wastewater reuse is a practice that has been gaining attention for the past few
decades as the world's population rises and water resources become scarce.
Wastewater application on soil can affect soil health, and the manner and extent
to which this occurs depends heavily on soil type and water quality. This study
compared the long-term (15+ years) effects and suitability of using secondary
level treated municipal wastewater and brackish groundwater for irrigation on the
water holding capacity of a clayey, calcareous soil on a cotton farm near San
Angelo, Texas. The soil-water holding properties were determined from the
extracted hydrostructural parameters of the two characteristic curves: water
retention curve and soil shrinkage curve based on the pedostructure concept. In
the pedostructure concept, these hydrostructural parameters are characteristic
properties of the soil aggregates structure and its thermodynamic interactions
with water. Results indicate that use of secondary treated wastewater increased
available water capacity in the top horizon (0-15 cm) and decreased the available
water holding capacity of this particular soil in the sub-horizons (15-72 cm).
The brackish groundwater irrigation resulted in no effect on available water
capacity in the top horizon, but significantly decreased it in the sub-horizons
as well. The rainfed soil was the healthiest soil in terms of water holding
capacity, but rainfall conditions do not produce profitable cotton yields.
Whereas, treated wastewater irrigated soil is producing the highest yields for
the farmer. Thus, this treated wastewater source and irrigation system can serve
as a suitable irrigation alternative to using brackish groundwater, enhancing the
water resource sustainability of this region.
PMID- 29958170
TI - Enantiomeric profiling of amphetamine and methamphetamine in wastewater: A 7-year
study in regional and urban Queensland, Australia.
AB - Enantiomeric profiling was used in this study to investigate the consumption of
amphetamine and methamphetamine in regional and urban Southeast Queensland,
Australia over a period of seven years. S(+) methamphetamine was predominantly
consumed in both urban and regional areas, showing a two and three fold increase
in urban and regional catchments respectively between 2011 and 2017. The ratio of
amphetamine to methamphetamine (AMP/METH) in wastewater reflected the expected
excretion profile of methamphetamine consumption indicating the presence of
amphetamine in this study was primarily the result of methamphetamine metabolism.
However, the occasional occurrence of R(-) amphetamine in samples containing
higher AMP/METH ratios, suggested the consumption of racemic amphetamine. The R(
) methamphetamine enantiomer was also identified in several samples, possibly
indicative that the phenyl-2-propanone (P2P) synthesis process rather than the
more typical reduction of ephedrines was also being used to manufacture
methamphetamine. Furthermore, we identified two samples with a significantly
different enantiomer ratio for the METH and AMP as well as a much lower AMP/METH
concentration ratio suggesting contribution from direct disposal of
methamphetamine into the sewer. This study demonstrated that enantiomeric
profiling in wastewater-based epidemiology can provide valuable information for
evaluating the origin of amphetamine in wastewater as either a metabolite of
methamphetamine consumption or amphetamine itself.
PMID- 29958171
TI - Cyanobacteria dynamics in a small tropical reservoir: Understanding spatio
temporal variability and influence of environmental variables.
AB - Anthropogenic disturbances within or near aquatic ecosystems often contribute to
eutrophication events. Cyanobacteria are a key group responsible for
environmental problems associated with eutrophication processes. Interest is
growing in estimating the threat of cyanobacteria in tropical Africa, however,
there is still a lack of understanding regarding temporal drivers of
cyanobacteria dynamics in natural aquatic ecosystems given the paucity of
relevant fundamental research in this area. To better understand cyanobacteria
dynamics, potential drivers of cyanobacteria dynamics were investigated in a
model tropical reservoir system, whereby phytoplankton communities and water
quality parameters were sampled during the tropical hot-wet, cool-dry and hot-dry
seasons. Fifteen cyanobacteria taxa were recorded over the study period.
Microcystis spp. and Cylindrospermopsis spp., known cyanotoxins producers, were
the most prevalent bloom-forming taxa found in the study, with overall
Cyanobacteria relative abundances being greatest during the cool-dry season. This
was likely driven by decreased river inflows and increased reservoir mixing
during the cool-dry period. Combinations of macrophyte cover, dissolved oxygen
levels, water transparency, reactive phosphorus, water depth and chemical oxygen
demand were found to significantly affect cyanobacteria community structure. The
study highlights that under climate change forecasts (for much of tropical arid
Africa), potentially harmful and problematic algal species may proliferate.
Management options, therefore, need to be explored to maintain water quality and
potable availability to mitigate against indirect harmful effects of
environmental changes on ecosystems and human communities that utilise their
services.
PMID- 29958172
TI - Dynamic response of biofilm microbial ecology to para-chloronitrobenzene
biodegradation in a hydrogen-based, denitrifying and sulfate-reducing membrane
biofilm reactor.
AB - The dynamic response of biofilm microbial ecology to para-chloronitrobenzene (p
CNB) biodegradation was systematically evaluated according to the composition and
loading of electron acceptors and H2 availability (controlled by H2 pressure) in
a hydrogen-based, denitrifying and sulfate-reducing membrane biofilm reactor
(MBfR). To accomplish this, a laboratory-scale MBfR was set up and operated with
different influent p-CNB concentrations (0, 2, and 5 mg p-CNB/L) and H2 pressures
(0.04 and 0.05 MPa). Polymerase chain reaction-denaturing gel electrophoresis
(PCR-DGGE) and cloning were then applied to investigate the bacterial diversity
response of biofilm during p-CNB biodegradation. The results showed that
denitrification and sulfate reduction largely controlled the total demand for H2.
Additionally, the DGGE fingerprint demonstrated that the addition of p-CNB, which
acted as an electron acceptor, was a critical factor in the dynamics of the MBfR
biofilm microbial ecology. The presence of p-CNB also had a more advantageous
effect on the biofilm microbial community. Additionally, clone library analysis
showed that Proteobacteria (especially beta- and gamma-) comprised the majority
of the microbial biofilm response to p-CNB biodegradation, and that Pseudomonas
sp. (Gammaproteobacteria) played a significant role in the biotransformation of p
CNB to aniline.
PMID- 29958173
TI - Assessment, mapping, and management of health risk from nitrate accumulation in
onion for Iranian population.
AB - Excess accumulation of nitrate in vegetable crops is normally related to the
excessive use of nitrogen fertilizers applied in agricultural fields. This study
was performed to evaluate the level of nitrate concentration in onion production
in Isfahan province of Iran and the potential health risks associated with high
level of nitrate in this crop, as an example of a case-study. The risk was
estimated by using the United States Environmental Protection Agency (USEPA)
method and presented as risk maps. Additionally, the impact of an improved
fertilizer management practice in selected vulnerable fields for reducing nitrate
concentration in onion production was evaluated. For this assessment, four
different onion fields in which onion bulb nitrate concentration was higher than
the safety level (70 mg kg-1 FW), provided by Welch (2003) in a survey study,
were chosen. The risk maps showed that despite higher risk possibility in adults,
in comparison with children, all values were lower than the acceptable level.
Further, the split application of nitrogen fertilizers in all fields
significantly reduced plant nitrate concentration with no reduction in yield and
even observed increase in the overall economic yield production. Therefore,
considering crop yields and nitrate accumulation impacts, improved nitrogen
management could provide an opportunity to promote onion crop production while
reducing negative health effects in high-risk regions in Isfahan province of
Iran.
PMID- 29958174
TI - Transcriptomic analysis of zebrafish (Danio rerio) embryos to assess integrated
biotoxicity of Xitiaoxi River waters.
AB - Assessing the toxicity posed by mixtures of unknown chemicals to aquatic
organisms is challenging. In this study, water samples from six cross-sections
along the Xitiaoxi River Basin (XRB) were monthly or bimonthly collected in 2014.
The year-period physiochemical parameters as well as one-month-water sample based
acute biotoxicity tests showed that the river water quality of the year was
generally in a good status. High performance liquid chromatography (HPLC)
screening based on one-month-water samples suggested that the organic pollutants
might be non-to-moderately-polar chemicals in very low concentrations. One-month
water sample based RNA-seq was performed to measure the mRNA differential
expression profile of zebrafish larvae to furtherly explore the potential
bioeffect and the spatial water quality change of the river. Result indicated
that the number of deferentially expressed genes (DEGs) tended to increase along
the downstream direction of the river. Gene ontology (GO) enrichment analysis
implied that the key pollutants might mainly be the function disruptors of
biological processes. Principle components analysis (PCA) combining with
transcripts and one-month-water sample based physiochemical parameters indicated
that the pollution might be similar at TP, DP and CTB sites while pollution
homology existed on some extent between YBQ and JW sites. Although the water
quality of the river had a complex time-space alternation during the year, and
the one-month-data based RNA-seq could not reflex the whole year-water quality of
a watershed, the gene expression profile via RNA-seq provided an alternative way
for assessing integrated biotoxicity of surface water, and it was relatively fit
for early-warning of water quality of a watershed with unobservable acute
toxicity. However, the identification of detail toxicants and the links between
DEGs and pollution level as well as physiological-biochemical toxicity needed
further investigation.
PMID- 29958175
TI - Intravascular Ultrasound Assessment and Correlation With Angiographic Findings
Demonstrating Femoropopliteal Arterial Dissections Post Atherectomy: Results From
the iDissection Study.
AB - BACKGROUND: Dissections occur post atherectomy of the infrainguinal arteries. We
hypothesized that angiography under-estimates their presence significantly.
METHODS: In this prospective pilot study, a total of 15 patients were evaluated
by intravascular ultrasound (IVUS) following treatment of femoropopliteal de novo
or non-stent restenosis using atherectomy. Eagle Eye Platinum ST IVUS catheters
(Philips) were used in this study. Thirteen Jetstream XC atherectomy devices
(Boston Scientific) and 2 investigational B-laser atherectomy devices (Eximo
Medical) were used. Cine and IVUS images were obtained at baseline, after
atherectomy, and after adjunctive balloon angioplasty. Angiographic and IVUS core
labs analyzed the images. RESULTS: Mean age was 70.6 +/- 8.0 years. Diabetes and
claudication were present in 60% and 73%, respectively. Mean baseline, post
atherectomy, and post-adjunctive angioplasty stenosis severity was 71.4%, 38.1%,
and 19.7%, respectively (P<.001 for both baseline vs post atherectomy and post
atherectomy vs adjunctive angioplasty). Lesion length was 108.5 +/- 43.1 mm.
Forty-six dissections were identified on IVUS post atherectomy vs 8 dissections
on angiogram (P<.01) (ratio, 5.75 to 1). Post adjunctive angioplasty, there were
39 dissections on IVUS vs 11 on angiogram (P<.01) (ratio, 3.55 to 1). Of these
dissections, 13% and 30.8% were >=180 degrees in circumference post atherectomy
and adjunctive balloon angioplasty, respectively (P=.047). Also, 39.1% and 33.3%
involved the media and/or adventitia as seen on IVUS post atherectomy and
adjunctive balloon angioplasty, respectively (P=.58). Longer lesions correlated
with more dissections post atherectomy on IVUS (P=.03), but not on angiogram
(P=.28). CONCLUSION: Dissections post atherectomy are grossly under-appreciated
on angiogram when compared to IVUS. A multicenter registry correlating these
findings with clinical outcomes is needed.
PMID- 29958176
TI - Radial Versus Femoral Approach for Percutaneous Coronary Intervention: MACE
Outcomes at Long-Term Follow-up.
AB - OBJECTIVE: To compare the main outcomes of radial versus femoral access at long
term follow-up. BACKGROUND: Little is known about the long-term major
cardiovascular events and bleeding complications of patients undergoing
percutaneous coronary intervention (PCI) with radial vs femoral approach.
METHODS: A total of 1107 patients from the CENTURY II trial were included. To
minimize baseline differences between radial and femoral groups, we applied
propensity-score matching for this comparison. RESULTS: In this multicenter
study, the radial approach was used in 73.4% of patients. After propensity-score
matching, baseline and procedural characteristics were comparable between both
groups. Procedural success was high and similar in radial and femoral approaches
(98.2% vs 97.5%; P=.47) while radial access was associated with a shorter
hospital stay (1.69 +/- 1.92 days vs 2.08 +/- 1.98 days; P<.01). The short-term
bleeding and vascular complication rates were significantly lower in the radial
group (1.7% vs 6.2% [P<.001 in-hospital] and 2.7% vs 9.6% [P<.001 at 1-month
follow-up]). At 3-year follow-up, radial access was associated with lower rates
of all-cause mortality (3.9 vs 6.9%; P=.04) and cardiovascular death (2.1 vs
4.9%; P=.02). The composite of all-cause mortality, myocardial infarction, and
revascularization showed no differences between groups (18.2 vs 21.1%; P=.29).
CONCLUSIONS: Compared to the femoral approach, the radial approach is associated
with significantly lower long-term all-cause mortality rate as well as lower in
hospital and short-term bleeding rates. These results suggest additional long
term benefits of radial access for PCI, but should be interpreted within the
context of the current study and further verified in future studies.
PMID- 29958177
TI - Orbital Atherectomy of Severely Calcified Unprotected Left Main Coronary Artery
Disease: One-Year Outcomes.
AB - OBJECTIVE: We assessed the 1-year outcomes of patients who underwent orbital
atherectomy for severely calcified unprotected left main coronary artery (ULMCA)
disease. BACKGROUND: The standard of care for ULMCA is coronary artery bypass
graft surgery. Percutaneous coronary intervention (PCI) is a reasonable option
for the treatment for ULMCA disease, especially in patients who are not good
candidates for surgical revascularization. Coronary artery calcification is
associated with worse clinical outcomes in patients who undergo PCI. Modification
of severely calcified plaque with orbital atherectomy facilitates stent delivery
and expansion. Data on intermediate outcomes of patients with ULMCA disease who
undergo orbital atherectomy are unknown. METHODS: We retrospectively evaluated 62
patients who underwent PCI with orbital atherectomy for ULMCA disease. The
primary endpoint was the major cardiac and cerebrovascular event (MACCE) rate,
which was the composite of cardiac death, myocardial infarction, target-lesion
revascularization, and stroke at 1 year. RESULTS: Distal bifurcation disease was
present in 71.0%, and a single-stent strategy was used in 90.5%. No patients
experienced coronary perforation or no-reflow. Two patients experienced coronary
dissection (3.2%). One patient experienced BARC-2 bleeding (1.6%). At 1 year, the
MACCE rate was 11.3%, with cardiac death occurring in 1.6%, myocardial infarction
in 8.1%, and target-lesion revascularization in 4.8%. Non-cardiac death occurred
in 4.8%. No patient experienced stroke or stent thrombosis. CONCLUSION: Orbital
atherectomy is an acceptable treatment option for patients with severely
calcified ULMCA disease, especially if patients are deemed too high risk for
surgical revascularization.
PMID- 29958178
TI - Difficult Retrieval of a Broken Catheter From a Total Implantable Venous Access
Device.
AB - A broken TIVAD catheter segment was discovered lodged within the right ventricle
of a man presenting with chest pain. The catheter removal is detailed.
PMID- 29958179
TI - Mother-and-Child Catheter-Induced Retrograde Dissection of the Left Main Coronary
Artery During Optical Coherence Tomography Examination.
AB - Optimal GuideLiner positioning for OCT acquisition in tortuous vessels requires
special attention to avoid iatrogenic dissection.
PMID- 29958180
TI - Optical Coherence Tomography for Guiding Plaque Stabilization in a Patient With
Myocardial Infarction and Massive Coronary Thrombosis.
AB - An OCT-guided watchful-waiting strategy is used to avoid the invasive treatment
of the LMCA in a very young patient with massive coronary thrombosis.
PMID- 29958181
TI - Chest Pain During Chemotherapy: A Case of Severe Myocardial Bridging.
AB - A cancer patient presented with acute chest pain at rest 40 hours after IV
fluorouracil infusion. Angiography showed evidence of myocardial bridging.
PMID- 29958182
TI - Successful Transcatheter Aortic Valve Replacement Using Balloon-Expandable Valve
for Pure Native Aortic Valve Regurgitation in the Presence of Ascending Aortic
Dissection.
AB - The use of balloon-expandable prosthesis in the treatment of native aortic valve
regurgitation in the presence of ascending aortic dissection is described.
PMID- 29958183
TI - Diazoxide toxicity in a child with persistent hyperinsulinemic hypoglycemia of
infancy: mixed hyperglycemic hyperosmolar coma and ketoacidosis.
AB - BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), also
known as congenital hyperinsulinism, has been known to go into spontaneous
remission, with patients developing diabetes in later life. A temporary phase of
hyperglycemia is, however, rarely reported. CASE PRESENTATION: We describe a 16
month-old child, a known case of diazoxide responsive PHHI, presenting with mixed
hyperglycemic hyperosmolar coma and ketoacidosis with rhabdomyolysis while on
diazoxide treatment. The patient required temporary cessation of diazoxide and
initiation of insulin infusion, followed by a relapse of hypoglycemia again
necessitating diazoxide therapy. CONCLUSIONS: Hyperosmolar coma with ketoacidosis
is a rare side-effect of diazoxide therapy, documented even in patients with
persistent hyperinsulinemic hypoglycemia of infancy.
PMID- 29958184
TI - Reply to: Congenital Zika syndrome in non-endemic regions: A neuroimaging pattern
based approach.
PMID- 29958185
TI - The prevalence of recurrent pain in childhood is high and increases with age.
PMID- 29958186
TI - Osteotome Sinus Floor Elevation Without Grafting: A 10-Year Clinical and Cone
Beam Sinus Assessment.
AB - PURPOSE: To evaluate the thickness of the sinus membrane in contact with implants
inserted 10 years before using an augmentation procedure without grafting
material, and to identify adverse events correlated with implant protrusion in
the sinus. MATERIALS AND METHODS: Osteotome sinus floor elevations were performed
without grafting material. The implants (Straumann AG, Basel, Switzerland) were
placed simultaneously, all protruded into the sinus. After 10 years, implants
were considered viable in the absence of mobility, pain, infection, or continued
radiolucency. Sinus health was assessed using cone-beam computed tomography and
by the way of a questionnaire in which patients reported symptoms of sinusitis
they might have had. RESULTS: Controlled implants (21 implants, 13 patients) were
osseointegrated. The membrane thickness was <2 mm in 11 patients and 2 to 3 mm
with flat thickening in 2 patients. No patients exhibited any clinical or
radiographic signs of sinusitis. CONCLUSIONS: No sinus complications were
observed after 10 years. The initial protrusion of implants into the sinus did
not influence long-term sinus health. The maintenance of successful integration
is thus the key to avoiding sinus complication.
PMID- 29958187
TI - U-Shaped Bone Splitting and Osteotome Techniques for Narrow Alveolar Ridge in
Implant Surgery.
AB - PURPOSE: Bone splitting and osteotome are common ridge expansion choices for
patients with a narrow alveolar ridge requiring dental implant restoration.
Despite the effectiveness of the 2 techniques in horizontal ridge augmentation,
they could also result in severe complications, which is thus considered a
contraindication. MATERIALS AND METHODS: A modification of the bone splitting and
the osteotome techniques is proposed hereby as an alternative. RESULTS: The
modified procedure reduces the tension of labial bone plate by creating a partial
bone fracture at the most depressed area of labial defect where the thinner bone
exists. CONCLUSIONS: This technique is primarily useful for cases with a facial
concavity. The modification could prevent iatrogenic labial bone defect during
the surgery, and compared with onlay bone grafting, it may shorten the overall
treatment time and avoid traumatizing the bone donor site.
PMID- 29958188
TI - Effects of Platelet Concentrates Used in Alveolar Ridge Preservation: A
Systematic Review.
AB - OBJECTIVE: The purpose of the review was to investigate the efficacy of platelet
concentrates (containing pure platelet-rich plasma, leukocyte- and platelet-rich
plasma, pure platelet-rich fibrin, and leukocyte- and platelet-rich fibrin) used
in alveolar ridge preservation (ARP), especially the changes in alveolar width
and height. DATA SOURCES: Randomized clinical trials that compared the efficiency
of platelet concentrates used in ARP were searched till June 2017 in 6 databases:
PubMed, Cochrane Central Register of Controlled Trials, EMBOSE, EMBASE, Web of
Sciences, and AMED. A meta-analysis would be performed if the heterogeneity was
acceptable. RESULTS: Five articles were included in the qualitative analysis. A
meaningful meta-analysis could not be performed because of the obvious
heterogeneities among studies. Three studies showed that leukocyte- and platelet
rich fibrin had a benefit in preserving ridge width or height or both, whereas 2
studies showed that platelet-rich plasma had no significant benefit. CONCLUSION:
The effects of different kinds of platelet concentrates used in ARP might be
different. Leukocyte- and platelet-rich fibrin might have a more positive effect
on alveolar width and height preservation than platelet-rich plasma. However,
randomized clinical trials included in the review were few and the strong
evidence on this topic was not yet enough.
PMID- 29958189
TI - Validity of Diagnostic Coding of Alcohol Intoxication Associated With Student
University Hospital Emergency Department Visits.
PMID- 29958190
TI - Time spent with HIV viral load above 1500 copies/ml among patients in HIV care,
2000-2014.
AB - OBJECTIVE: Sexual HIV transmission is more likely to occur when plasma HIV RNA
level (viral load) exceeds 1500 copies/ml. We assessed the percentage of person
time spent with viral load above 1500 copies/ml (pPT >1500) among adults with HIV
in care. DESIGN: Observational cohort in eight United States HIV clinics.
METHODS: Participants had at least one HIV Outpatient Study (HOPS) clinic visit
and at least two viral loads during 2000-2014. We assessed pPT above 1500 in time
intervals between consecutive viral load pairs, overall and by ART status. Trends
in pPT above 1500 and associations between pPT above 1500 and chosen baseline
demographics and clinical characteristics were analyzed using generalized
estimating equations. RESULTS: There were 5873 patients contributing 37 794
person-years; 86.0% person-years had prescribed ART, with increasing coverage
over time. Over 2000-2014 pPT above 1500 was 24.2%, decreasing from 38.3% in 2000
2002 to 11.3% in 2012-2014. During observation time with ART prescribed, pPT
above 1500 was 16.4% overall, decreasing from 29.9% in 2000-2002 to 8.0% in 2012
2014. pPT above 1500 was higher in patients less than 35 vs. at least 50 years
old (31.5 vs. 15.6%), women vs. men (30.8 vs. 22.3%), and black vs. white and
Latino/Hispanic patients (32.7 vs. 19.9 and 23.7%, respectively). Multivariable
correlates of higher pPT above 1500 included no prescribed ART, being younger,
non-Hispanic black vs. white, baseline viral load above 1500 copies/ml or lower
CD4 count, and baseline public vs. private insurance. CONCLUSION: pPT above 1500
declined during 2000-2014. Results support decreasing HIV transmission risk from
persons in HIV care over the last decade, and the need to focus interventions on
patient groups more consistently viremic.
PMID- 29958191
TI - Erratum: High-dimensional Propensity Score Adjustment in Studies of Treatment
Effects Using Health Care Claims Data.
PMID- 29958192
TI - The Authors Respond.
PMID- 29958194
TI - Re: "Sex-Specific Prognostic Significance of Obesity in Nonmetastatic Clear-Cell
Renal-Cell Carcinoma in Korea".
PMID- 29958193
TI - Re: Multivessel Percutaneous Coronary Intervention in Patients with ST-Segment
Elevation Myocardial Infarction with Cardiogenic Shock.
PMID- 29958195
TI - Histopathologic study from a colorectal cancer screening in Chile: results from
the first 2 years of an international collaboration between Chile and Japan.
AB - A national colorectal cancer (CRC) screening program began in Chile in 2012,
which is an international collaboration between Japan and Chile and is based on a
standardized protocol supported by Tokyo Medical and Dental University. We
describe the results from the first 2 years of screening at one public hospital
in Punta Arenas, Chile. Of 4124 asymptomatic individuals aged between 50 and 75
years, 485 participants with immunological fecal occult blood test values of at
least 100 ng/ml and/or those with family histories of CRC underwent
colonoscopies. Lesions were found in 291 participants, and 642 histologic samples
were obtained. Chilean pathologists made the initial histologic diagnoses, and a
Japanese pathologist reviewed the histologic slides and analyzed the results. Of
the 291 participants with lesions, 60 (20.6%) were diagnosed with
adenocarcinomas, of which 50 (83.3%) were early-phase adenocarcinomas (pTis or
pT1), and 163 (56.0%) were diagnosed with conventional adenomas, of which 96
(58.9%) were high-risk adenomas. The cancer prevalence within the screened
population was 1.5% (60 of 4124). The colonoscopy cancer detection rate was 12.4%
(60 of 485). Notably, we detected one flat-depressed (0-IIc) lesion that measured
5 mm and had invaded the submucosa. The findings from this screening program are
the first to show the histopathologic distributions of consecutive lesions and
the high incidence of CRC in Chile. The high detection rates for high-risk
adenomas and cancer support the feasibility of early CRC screening and its
potential to reduce the mortality associated with CRC.
PMID- 29958196
TI - Frontalis-Orbicularis Muscle Advancement for Correction of Upper Eyelid Ptosis: A
Systematic Literature Review.
AB - PURPOSE: To review the level of standardization of frontalis-orbicularis muscle
advancement to correct severe blepharoptosis and the degree of scientific
evidence supporting the procedure as a useful modality of blepharoptosis repair.
METHODS: The authors searched the Medline, Lilacs, and Scopus databases for all
articles in English, Spanish, and French that used as keywords the terms
"frontalis muscle flap," "orbicularis muscle flap," and "ptosis." Data retrieved
included authorship specialty, geographic region where the surgeries were
performed, characteristics of the samples reported, type and dimensions of the
flaps used, time of follow-up, rate of undercorrection, and complications.
RESULTS: Thirty-eight articles were retrieved and analyzed. Most studies
originated from Asian countries, especially China, Taiwan, and Korea. Many
variations of the procedure were encountered, including location of incisions and
frontalis flap design. There were 23 case series with more than 10 patients. None
compared the procedure to conventional frontalis suspension surgery. The samples
were not homogeneous, including patients with different type of ptosis, variable
degrees of levator function, and using distinct methods of evaluating eyelid
position. Undercorrection rates ranged from 1.8% to 38% with a median value of
12.2%. The rate of complications (eyelid crease abnormalities, entropion,
hematoma, and supraorbital nerve injury) was low. CONCLUSIONS: The direct
frontalis-orbicularis muscle advancement has been judged positively in all
reports analyzed. However, the level of standardization of the surgery is low,
and the reported series are not homogeneous. Further studies are needed to better
evaluate this operation.
PMID- 29958197
TI - Pulmonary Emphysema Quantification on Ultra-Low-Dose Computed Tomography Using
Model-Based Iterative Reconstruction With or Without Lung Setting.
AB - OBJECTIVES: To evaluate the influence of model-based iterative reconstruction
(MBIR) with lung setting and conventional setting on pulmonary emphysema
quantification by ultra-low-dose computed tomography (ULDCT) compared with
standard-dose CT (SDCT). METHODS: Forty-five patients who underwent ULDCT (0.18
+/- 0.02 mSv) and SDCT (6.66 +/- 2.69 mSv) were analyzed in this retrospective
study. Images were reconstructed using filtered back projection (FBP) with smooth
and sharp kernels and MBIR with conventional and lung settings. Extent of
emphysema was evaluated using fully automated software. Correlation between ULDCT
and SDCT was assessed by interclass correlation coefficiency (ICC) and Bland
Altman analysis. RESULTS: Excellent correlation was seen between MBIR with
conventional setting on ULDCT and FBP with smooth kernel on SDCT (ICC, 0.97;
bias, -0.31%) and between MBIR with lung setting on ULDCT and FBP with sharp
kernel on SDCT (ICC, 0.82; bias, -2.10%). CONCLUSION: Model-based iterative
reconstruction improved the agreement between ULDCT and SDCT on emphysema
quantification.
PMID- 29958198
TI - Single-Shot Coronary Quiescent-Interval Slice-Selective Magnetic Resonance
Angiography Using Compressed Sensing: A Feasibility Study in Patients With
Congenital Heart Disease.
AB - OBJECTIVE: The aim of this study was to determine whether it is feasible to
visualize the coronary origins in patients with congenital heart disease (CHD)
using single-shot coronary quiescent-interval slice-selective (QISS) magnetic
resonance angiography (MRA) with compressed sensing (CS). METHODS: This
retrospective study leveraged a parent study, which aimed to compare breath-hold,
2.1-fold accelerated, 2-shot coronary QISS MRA and clinical standard contrast
enhanced (CE) MRA in 14 patients with CHD (mean age, 17.0 +/- 8.6 years, 6
females and 8 males). We evaluated the feasibility of single-shot coronary QISS
MRA by retrospectively undersampling the 2-shot data set by an additional factor
of 2, performing CS reconstruction, and comparing the retrospectively derived
single-shot QISS MRA to 2-shot coronary QISS MRA and clinical standard CE MRA.
For quantitative analysis, structural similarity index and normalized root mean
square error were calculated. For qualitative analysis, 2 experienced readers
scored the conspicuity of coronary origins on a 5-point Likert scale (1 =
nondiagnostic, 2 = poor, 3 = clinically acceptable, 4 = good, 5 = excellent).
RESULTS: Compared with 2-shot QISS, single-shot QISS produced normalized root
mean square error of 5.8% +/- 0.8% and structural similarity index of 95.4% +/-
1.6%, suggesting high data fidelity by CS reconstruction. Compared with the mean
conspicuity scores for clinical CE MRA (4.2 +/- 0.5 and 4.1 +/- 0.6 for right and
left coronary origins, respectively), the mean conspicuity scores were not
significantly different (P > 0.3) for 2-shot QISS (4.4 +/- 0.9 and 4.2 +/- 1.1,
respectively) and single-shot QISS with CS (4.3 +/- 1.1 and 3.8 +/- 1.3,
respectively) and deemed clinically acceptable to good (scores >=3.0).
CONCLUSIONS: This study shows that it is feasible to visualize the coronary
origins in patients with CHD with clinically acceptable to good image quality
using single-shot coronary QISS MRA with CS.
PMID- 29958200
TI - Intrahepatic Splenosis: Incidental Liver Lesion after Splenectomy.
AB - We describe the case of a 50-year-old man with history of remote splenectomy who
underwent routine lung cancer screening chest computed tomography and was
incidentally found to have a liver lesion. Dedicated liver protocol computed
tomography demonstrated "archiform" enhancement pattern in the arterial phase and
homogenous filling-in enhancement on portal venous and delayed phases. Multiple
other smaller enhancing intraperitoneal lesions were also found. These findings
along with history of splenectomy confirmed a diagnosis of intrahepatic and
intraperitoneal splenosis and helped avoid biopsy. Intrahepatic splenules can be
challenging to diagnose owing to its unusual location and similarity in
appearance to a liver neoplasm or metastasis. However, careful evaluation of
enhancement pattern and review of medical history can lead to an accurate
diagnosis and avoidance of invasive biopsy.
PMID- 29958199
TI - Diagnostic Value of Diffusion-Weighted Imaging and Apparent Diffusion Coefficient
in Assessment of the Activity of Crohn Disease: 1.5 or 3 T.
AB - OBJECTIVE: The objective of this study is to evaluate the role of diffusion
weighted imaging (DWI) in assessment of the activity of Crohn disease (CD) and to
explore differences between DWI in 3 T and 1.5 T. METHODS: Postcontrast magnetic
resonance enterography with DWI of 72 patients with pathological proof of CD was
retrospectively evaluated for restricted diffusion qualitatively and quantitavely
in 3 T (n = 40) and 1.5 T (n = 32). Magnetic resonance activity score of 7 or
higher was used as reference of activity. RESULTS: Fifty-five patients had active
lesions. Diffusion-weighted imaging hyperintensity showed sensitivity (100%,
100%) and specificity (88.89%, 100%) in 1.5/3 T for activity assessment. Mean +/-
SD apparent diffusion coefficient for active lesions was 1.21 +/- 0.42 and 1.28
+/- 0.59 * 10 mm/s in 1.5 and 3 T, respectively. The proposed cutoff values of
1.35 and 1.38 * 10 mm/s in 1.5 and 3 T, respectively, had sensitivity (80%, 93%),
specificity (100%, 90%), accuracy (88%, 93%), and no significant difference in
accuracy between 1.5/3 T (P = 0.48). CONCLUSIONS: Diffusion-weighted imaging
hypersensitivity and apparent diffusion coefficient values accurately assessed
the activity of CD. No significant statistical difference in diagnostic accuracy
was detected between 1.5 and 3 T.
PMID- 29958201
TI - Functional Balance Testing in Cervical Spondylotic Myelopathy Patients.
AB - STUDY DESIGN: A prospective cohort study. OBJECTIVE: Quantify the amount of sway
associated with maintaining a balanced posture in a group of untreated cervical
spondylotic myelopathy (CSM) patients. SUMMARY OF BACKGROUND DATA: Balance is
defined as the ability of the human body to maintain its center of mass (COM)
within the base of support with minimal postural sway. Sway is the movement of
the COM in the horizontal plane when a person is standing in a static position.
CSM patients have impaired body balance and proprioceptive loss. METHODS: Thirty
two CSM patients performed a series of functional balance tests a week before
surgery. Sixteen healthy controls (HC) performed a similar balance test. Patients
are instructed to stand erect with feet together and eyes opened in their self
perceived balanced and natural position for a full minute. All test subjects were
fitted to a full body reflective markers set and surface EMG. RESULTS: CSM
patients had more COM sway in the anterior-posterior (CSM: 2.87 vs. C: 0.74 cm; p
= 0.023), right-left (CSM: 5.16 vs. C: 2.51 cm; p = 0.003) directions as well as
head sway (anterior-posterior - CSM: 2.17 vs. C: 0.82 cm; p = 0.010 and right
left - CSM: 3.66 vs. C: 1.69 cm; p = 0.044), more COM (CSM: 44.72 cm vs. HC:
19.26 cm, p = 0.001) and head (Pre: 37.87 cm vs. C: 19.93 cm, p = 0.001) total
sway in comparison to controls. CSM patients utilized significantly more muscle
activity to maintain static standing, evidenced by the increased trunk and lower
extremity muscle activity (Multifidus, Erector Spinae, Rectus Femoris, and
Tibialis Anterior, p < 0.050) during one minute standing. CONCLUSIONS: In
symptomatic CSM patients, COM and head total sway were significantly greater than
controls. Individuals with CSM exhibit more trunk and lower extremity muscle
activity, and thus expend more neuromuscular energy to maintain a balanced,
static standing posture. This study is the first effort to evaluate global
balance as a dynamic process in this patient population. LEVEL OF EVIDENCE: 3.
PMID- 29958203
TI - Is There a Relationship Between Gestational Diabetes and Perinatal Depression?
AB - Perinatal depression (PND) is one of the leading complications associated with
childbirth. Early detection and treatment of depression, particularly during the
perinatal period, is essential for the promotion of positive maternal-child
outcomes. Gestational diabetes mellitus (GDM) has been suggested as a confounding
factor associated with PND. Concerns associated with PND include interference
with maternal-newborn bonding and long-term effects of neurobehavioral
consequences. An exemplar case describing one woman's experience with GDM and her
subsequent complications associated with PND is presented to discuss maternal
depression and its plausible association with GDM. Recommendations include
universal screening with the validated Edinburgh Postnatal Depression Scale
screening tool during the early perinatal period to reduce incidence of maternal
newborn complications associated with PND and promote underpinnings for best
practice.
PMID- 29958202
TI - Balloon Kyphoplasty Versus Conservative Treatment for Acute Osteoporotic
Vertebral Fractures with Poor Prognostic Factors: Propensity-Score-Matched
Analysis Using Data From Two Prospective Multicenter Studies.
AB - STUDY DESIGN: Multicenter, prospective, single-arm, intervention study.
OBJECTIVE: To investigate efficacy of balloon kyphoplasty (BKP) for acute
osteoporotic vertebral fractures (OVFs) in patients with poor prognostic factors.
SUMMARY OF BACKGROUND DATA: The indications for BKP remain unclear.
Characteristic magnetic resonance imaging (MRI) findings (high-intensity or
diffuse low-intensity area in fractured vertebrae on T2-weighted images) were
reportedly predictive of delayed union. METHODS: This study enrolled 106 patients
with poor prognostic MRI findings who underwent BKP within 2 months after injury,
and 116 controls with acute OVFs and the same poor prognostic factors who
underwent conservative treatment. Patients were propensity-score-matched in a
logistic regression model adjusted for age, sex, number of baseline old
fractures, and fracture level. The primary outcome was reduction in activities of
daily living (ADLs) at 6 months after fracture, and the secondary outcomes were
improvement in short-form (SF)-36 subscales, back pain visual analog scale (VAS)
score, and vertebral body deformity. RESULTS: A decrease in ADLs occurred in 5.6%
of patients in the BKP group and 26.7% of patients in the conservative treatment
group (P < 0.001). The SF-36 vitality subscale score improved by 26.9 +/- 25.9
points in the BKP group and 14.5 +/- 29.4 points in the control group (P = 0.03).
The VAS pain score improved by 43.4 +/- 34.4 in the BKP group and 52.2 +/- 29.8
in the control group (P = 0.44). The vertebral body wedge angle improved by 5.5
+/- 6.2 degrees in the BKP group and -6.3 +/- 5.0 degrees in the control group
(P < 0.0001). The percent vertebral body height improved by 15.2 +/- 19.2% in the
BKP group and -20.6 +/- 14.2% in the control group (P < 0.0001). CONCLUSIONS:
ADLs, quality of life, and vertebral deformity showed greater improvement with
BKP intervention for acute OVF with poor prognostic factors than with
conservative treatment at 6 months after injury. Our treatment strategy uses BKP
intervention according to the presence or absence of poor prognostic MRI
findings. LEVEL OF EVIDENCE: 4.
PMID- 29958204
TI - Reproductive Coercion: Baby, If You Love Me...
AB - BACKGROUND AND PURPOSE: Reproductive coercion involves behavior that interferes
with the individual's unique ability to make decisions about their reproductive
health. The concept was first recognized in 2010. Reproductive coercion is
intended to maintain power and control in a relationship by someone past,
present, or future wishing to be involved in an intimate or dating relationship
with an adult or adolescent. Three forms of coercion have been identified:
contraceptive sabotage, pregnancy pressure, and control of pregnancy outcomes.
METHODS: A search for scientific literature was conducted examining studies
involving reproductive coercion as well as evidence-based interventions that
could be used by nurses in the clinic setting. CONCLUSIONS: Prevalence of
reproductive coercion is estimated to range from 8% to 16%. There is a high
association between intimate partner violence (IPV), sexually transmitted
infections (STIs), and unintended pregnancy. Adolescents are at greater risk for
reproductive coercion than older women. IMPLICATIONS FOR PRACTICE: There are
interventions we can incorporate into our clinical practices to screen and assess
women for reproductive coercion. Women experiencing reproductive coercion are at
risk for unintended pregnancy, STIs, IPV, and forced pregnancy outcomes.
PMID- 29958205
TI - Maternity Nurses' Knowledge and Practice of Breastfeeding in Mississippi.
AB - BACKGROUND: Mississippi has the lowest rates of breastfeeding of all states at 6
months and at 1 year. Registered nurses working in the maternity setting can be
influential in mothers' decision to breastfeed. PURPOSE: The purpose of this
study was to examine registered nurses' knowledge and practice related to
breastfeeding; and to identify facilitators and barriers to implementing the Ten
Steps to Successful Breastfeeding in Mississippi hospitals. METHODS: 302
Registered nurses working in hospital maternity/birthing settings in Mississippi
completed a questionnaire. Breastfeeding knowledge and practices overall scores
were categorized into: poor and good. Chi-square analysis and Spearman
correlations were used to determine correlations among the variables. RESULTS:
Overall breastfeeding knowledge and practices of respondents was good. Only 4%
earned a perfect score. Most believed they were effective (77%) in meeting the
needs of new mothers. Significant positive associations were noted among
knowledge and effectiveness, and other variables. Resistance to change and
staffing shortages were the main barriers to implementing the Ten Steps; raising
awareness about the importance of the Ten Steps and providing a lactation
consultant were the main facilitators. CONCLUSION: More research is needed to
understand reasons behind low breastfeeding rates in Mississippi.
PMID- 29958206
TI - Managing Gestational Diabetes Postpartum.
PMID- 29958207
TI - Mental Illness in Children and Adolescents: A Rising Concern on College Campuses.
PMID- 29958208
TI - The Need for Research in Pregnant and Lactating Women.
PMID- 29958209
TI - Reducing Hunger Among Women and Children in India.
PMID- 29958212
TI - Effects of an Interdisciplinary Practice Bundle for Second Stage Labor on
Clinical Outcomes.
PMID- 29958211
TI - Severe Maternal Morbidity and Maternal Mortality: What Can be Learned From
Reviewing Near Miss and Adverse Events?
PMID- 29958213
TI - Effective Communication Strategies for Nurses to Discuss Infant Feeding With New
Mothers During Postpartum Hospitalization.
PMID- 29958214
TI - Emergency Manual Implementation in a Large Academic Anesthesia Practice: Strategy
and Improvement in Performance on Critical Steps.
AB - BACKGROUND: The use of cognitive aids, such as emergency manuals (EMs), improves
team performance on critical steps during crisis events. In our large academic
anesthesia practice, we sought to broadly implement an EM and subsequently
evaluate team member performance on critical steps. METHODS: We observed the
phases of implementing an EM at a large academic anesthesia practice from 2013 to
2016, including the formation of the EM implementation team, identification of
preferred EM characteristics, consideration of institution-specific factors,
selection of the preferred EM, recognition of logistical barriers, and staff
education. Utilization of the EM was tested in a regular clinical environment
with all available resources using a standardized verbal simulation of 3 crisis
events both preimplementation and 6 months postimplementation. Individual members
of the anesthesia team were asked to verbalize interventions for specific crisis
events over 60 seconds. RESULTS: We introduced a customized version of the
Stanford Emergency Manual on January 26, 2015. Fifty-nine total participants
(equal proportion of anesthesiology attending physicians, resident physicians,
certified registered nurse anesthetists, and student registered nurse anesthetist
staff) were surveyed in the preimplementation phase and 60 in the 6-month
postimplementation phase. In the postimplementation phase, a minority (41.7%)
utilized the EM for the verbal-simulated crisis events. Those who used the EM
performed better than those who did not (median 21.0 critical steps out of a
possible 30 total steps [70.0%], interquartile range 19-25 vs 18.0 critical steps
verbalized [60.0%], interquartile range 16-20; P < .001). Among all subjects, the
median number of critical steps verbalized was 16 (53.3%) preimplementation and
19.5 critical steps (65.0%) postimplementation. CONCLUSIONS: Implementation of an
EM in a large academic anesthesia practice is not without challenges. While full
integration of the EM was not achieved 6 months after implementation,
verbalization of critical steps on 3 simulated crisis events improved when the EM
was utilized.
PMID- 29958215
TI - Epidural Analgesia and Subcutaneous Heparin 3 Times Daily in Cancer Patients With
Acute Postoperative Pain.
AB - The use of epidural analgesia in conjunction with subcutaneous administration of
unfractionated heparin 3 times per day could increase the risk of spinal epidural
hematoma, but insufficient patient experience data exist to determine this. We
retrospectively reviewed the incidence of spinal epidural hematoma in 3705 cases
at our institution over a 7-year period of patients receiving acute postoperative
epidural analgesia and heparin 3 times per day. No cases of spinal epidural
hematoma were reported (95% CI, 0-0.0009952).
PMID- 29958216
TI - Proceedings From the Society for Advancement of Blood Management Annual Meeting
2017: Management Dilemmas of the Surgical Patient-When Blood Is Not an Option.
AB - Vigilance is essential in the perioperative period. When blood is not an option
for the patient, especially in a procedure/surgery that normally holds a risk for
blood transfusion, complexity is added to the management. Current technology and
knowledge has made avoidance of blood transfusion a realistic option but it does
require a concerted patient-centered effort from the perioperative team. In this
article, we provide suggestions for a successful, safe, and bloodless journey for
patients. The approaches include preoperative optimization as well as
intraoperative and postoperative techniques to reduce blood loss, and also
introduces current innovative substitutes for transfusions. This article also
assists in considering and maneuvering through the legal and ethical systems to
respect patients' beliefs and ensuring their safety.
PMID- 29958217
TI - Prospective Observational Investigation of Capnography and Pulse Oximetry
Monitoring After Cesarean Delivery With Intrathecal Morphine.
AB - BACKGROUND: Intrathecal morphine provides excellent analgesia after cesarean
delivery; however, respiratory events such as apnea, bradypnea, and hypoxemia
have been reported. The primary study aim was to estimate the number of apneas
per subject, termed "apnea alert events" (AAEs) defined by no breath for 30-120
seconds, using continuous capnography in women who underwent cesarean delivery.
METHODS: We performed a prospective, observational study with institutional
review board approval of women who underwent cesarean delivery with spinal
anesthesia containing 150-ug intrathecal morphine. A STOP-Bang obstructive sleep
apnea assessment was administered to all women. Women were requested to use
continuous capnography and pulse oximetry for 24 hours after cesarean delivery.
Nasal sampling cannula measured end-tidal carbon dioxide (EtCO2) and respiratory
rate (RR), and oxygen saturation (SpO2) as measured by pulse oximetry.
Capnography data were defined as "valid" when EtCO2 >10 mm Hg, RR >5 breaths per
minute (bpm), SpO2 >70%, or during apnea (AAE) defined as "no breath" (EtCO2, <5
mm Hg) for 30-120 seconds. Individual respiratory variable alerts were 10-second
means of EtCO2 <10 mm Hg, RR <8 bpm, and SpO2 <94%. Nurse observations of RR
(hourly and blinded to capnography) are reported. RESULTS: We recruited 80 women,
mean (standard deviation [SD]) 35 (5) years, 47% body mass index >30 kg/m/weight
>90 kg, and 11% with suspected obstructive sleep apnea (known or STOP-Bang score
>3). The duration of normal capnography and pulse oximetry data was mean (SD)
(range) 8:28 (7:51) (0:00-22:32) and 15:08 (6:42) (1:31-23:07) hours:minutes,
respectively; 6 women did not use the capnography. There were 198 AAEs, mean (SD)
duration 57 (27) seconds experienced by 39/74 (53%) women, median (95% confidence
interval for median) (range) 1 (0-1) (0-29) per subject. Observation of RR by
nurses was >=14 bpm at all time-points for all women, r = 0.05 between
capnography and nurse RR (95% confidence interval, -0.04 to 0.14). There were no
clinically relevant adverse events for any woman. Sixty-five women (82%) had
complaints with the capnography device, including itchy nose, nausea,
interference with nursing baby, and overall inconvenience. CONCLUSIONS: We report
198 AAEs detected by capnography among women who underwent cesarean delivery
after receiving intrathecal morphine. These apneas were not confirmed by the
intermittent hourly nursing observations. Absence of observer verification
precludes distinction between real, albeit nonclinically significant alerts with
capnography versus false apneas. Discomfort with the nasal sampling cannula and
frequent alerts may impact capnography application after cesarean delivery. No
clinically relevant adverse events occurred.
PMID- 29958218
TI - Opioids for Acute Pain Management in Patients With Obstructive Sleep Apnea: A
Systematic Review.
AB - The intrinsic nature of opioids to suppress respiratory function is of particular
concern among patients with obstructive sleep apnea (OSA). The association of OSA
with increased perioperative risk has raised the question of whether patients
with OSA are at higher risk for opioid-induced respiratory depression (OIRD)
compared to the general population. The aims of this systematic review were to
summarize current evidence with respect to perioperative OIRD, changes in sleep
disordered breathing, and alterations in pain and opioid sensitivity in patients
with OSA. A systematic literature search of studies published between 1946 and
October 2017 was performed utilizing the following databases: Medline, ePub Ahead
of Print/Medline In-process, Embase, Cochrane Central Register of Controlled
Trials, Cochrane Database of Systematic Reviews, PubMed-NOT-Medline and
ClinicalTrials.Gov. Of 4321 initial studies, 40 met the inclusion criteria. The
Oxford level of evidence was assessed. Overall, high-quality evidence on the
comparative impact of acute opioid analgesia in OSA versus non-OSA patients is
lacking. The current body of evidence is burdened by significant limitations
including risk of bias and large heterogeneity among studies with regard to OSA
severity, perioperative settings, outcome definitions, and the presence or
absence of various perioperative drivers. These factors complicate an accurate
interpretation and robust analysis of the true complication risk. Nevertheless,
there is some consistency among studies with regard to a detrimental effect of
opioids in the presence of OSA. Notably, the initial 24 hours after opioid
administration appear to be most critical with regard to life-threatening OIRD.
Further, OSA-related increased pain perception and enhanced opioid sensitivity
could predispose patients with OSA to a higher risk for OIRD without overdosing.
While high-quality evidence is needed, retrospective analyses indicate that
critical, life-threatening OIRD may be preventable with a more cautious approach
to opioid use, including adequate monitoring.
PMID- 29958219
TI - Practice of Ultrasound-Guided Palpation of Neck Landmarks Improves Accuracy of
External Palpation of the Cricothyroid Membrane.
AB - BACKGROUND: Ultrasonography can accurately identify the cricothyroid membrane;
however, its impact on the subsequent accuracy of external palpation is not
known. In this study, we tested the ability of anesthesia participants to
identify the midpoint of the cricothyroid membrane using external palpation with
and without ultrasound (US)-guided practice. METHODS: Following institutional
ethics approval and informed consent, anesthesia participants consisting of
anesthesia residents, fellows, and practicing anesthesia assistants underwent
didactic teaching on neck landmarks. The participants were then randomized to
practice palpation of neck landmarks with US guidance (US group) or without
ultrasonography (non-US [NUS] group). After the practice session, each
participant identified the cricothyroid membrane using external palpation on the
neck of 10 volunteers and marked the anticipated entry point for device insertion
(palpation point [PT]). The midpoint of the cricothyroid membrane of each
volunteer had been premarked with invisible ink using ultrasonography (US point)
by a separate member of the research team. The primary outcome was the accuracy
rate defined as the percentage of the attempts with the distance <=5 mm measured
from the PT to US point for the participant. The primary outcome was compared
between NUS and US groups using Wilcoxon rank sum test. A mixed-effect logistic
regression or mixed-effect linear model was also conducted for outcomes
accounting for the clustering and adjusting for potential confounders. RESULTS:
Fifteen anesthesia participants were randomized to US (n = 8) and NUS (n = 7)
groups. A total of 80 and 61 attempts were performed by the US and NUS groups,
respectively. The median accuracy rate in the US group was higher than the NUS
group (65% vs 30%; P = .025), and the median PT-US distance in the US group was
shorter than in the NUS group (4.0 vs 8.0 mm; P = .04). The adjusted mean PT-US
distance in the US group was shorter compared to the NUS group (adjusted mean
[95% CI], 3.6 [2.9-4.6] vs 6.8 [5.2-8.9] mm; P < .001). CONCLUSIONS: Anesthesia
participants exposed to practice with US-guided palpation of the cricothyroid
membrane location were better able to identify the cricothyroid membrane using
only blind palpation than participants without US-guided practice. Practice with
US-guided palpation of neck landmarks improves subsequent blind localization of
the cricothyroid membrane using palpation alone.
PMID- 29958220
TI - Dexmedetomidine Versus Remifentanil for Monitored Anesthesia Care During
Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Randomized
Controlled Trial.
AB - BACKGROUND: We hypothesized that, compared to remifentanil, dexmedetomidine used
for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)
performed under monitored anesthesia care (MAC) in nonintubated patients would
result in fewer episodes of major respiratory adverse events (number of episodes
of bradypnea, apnea or desaturation) but no difference in satisfaction with
perioperative conditions. METHODS: Sixty (American Society of Anesthesiologists
physical status I-III) patients scheduled to undergo EBUS-TBNA under MAC were
randomized to receive either remifentanil (0.5 ug/kg IV bolus) in 10 minutes,
followed by 0.05-0.25 ug/kg/min, or dexmedetomidine (0.4 ug/kg IV bolus) in 10
minutes, followed by 0.5-1.0 ug/kg/h. The primary outcome was the number of major
respiratory adverse events (bradypnea, apnea, or hypoxia). The secondary outcomes
included hemodynamic variables, discharge time from the postanesthesia care unit,
endotracheal lidocaine use, patient's sedation using the Observer Assessment of
Alertness/Sedation Scale, operative conditions, operator and patient
satisfaction, pain, coughing, vocal cord mobility, recall, and nausea/vomiting.
RESULTS: Dexmedetomidine produced significantly fewer episodes of major
respiratory events (bradypnea, apnea, or desaturation), with 0 [0-0.5] episodes
versus 2 [0-5] (median [interquartile range]) (P = .001), than did remifentanil.
Fewer episodes of bradypnea or apnea (dexmedetomidine: 0 [0-0] versus
remifentanil: 0 [0-0.5]; P = .031), and fewer episodes of desaturation
(dexmedetomidine: 0 [0-0.5] versus remifentanil: 1 [0-4]; P = .039) were recorded
in the dexmedetomidine group. The time needed for patients to meet postanesthesia
care unit discharge criteria (Aldrete score: 9) after EBUS-TBNA was longer in the
dexmedetomidine group (10 [3-37.5] minutes) versus the remifentanil group (3 [3
5] minutes) (P < .001). No differences were observed in the 2 groups for sedation
depth (Observer Assessment of Alertness/Sedation Scale), endotracheal lidocaine
use, operative conditions, operator and patient satisfaction, pain, coughing,
vocal cord mobility, recall, and nausea/vomiting episodes. CONCLUSIONS:
Dexmedetomidine resulted in fewer respiratory adverse events during EBUS-TBNA
under MAC, when compared to remifentanil, with no difference in overall operative
conditions. However, dexmedetomidine use was associated with delayed
postoperative discharge.
PMID- 29958221
TI - Potent Inactivation-Dependent Inhibition of Adult and Neonatal NaV1.5 Channels by
Lidocaine and Levobupivacaine.
AB - BACKGROUND: Cardiotoxic effects of local anesthetics (LAs) involve inhibition of
NaV1.5 voltage-gated Na channels. Metastatic breast and colon cancer cells also
express NaV1.5, predominantly the neonatal splice variant (nNaV1.5) and their
inhibition by LAs reduces invasion and migration. It may be advantageous to
target cancer cells while sparing cardiac function through selective blockade of
nNaV1.5 and/or by preferentially affecting inactivated NaV1.5, which predominate
in cancer cells. We tested the hypotheses that lidocaine and levobupivacaine
differentially affect (1) adult (aNaV1.5) and nNaV1.5 and (2) the resting and
inactivated states of NaV1.5. METHODS: The whole-cell voltage-clamp technique was
used to evaluate the actions of lidocaine and levobupivacaine on recombinant
NaV1.5 channels expressed in HEK-293 cells. Cells were transiently transfected
with cDNAs encoding either aNaV1.5 or nNaV1.5. Voltage protocols were applied to
determine depolarizing potentials that either activated or inactivated 50% of
maximum conductance (V1/2 activation and V1/2 inactivation, respectively).
RESULTS: Lidocaine and levobupivacaine potently inhibited aNaV1.5 (IC50 mean
[SD]: 20 [22] and 1 [0.6] MUM, respectively) and nNaV1.5 (IC50 mean [SD]: 17 [10]
and 3 [1.6] MUM, respectively) at a holding potential of -80 mV. IC50s differed
significantly between lidocaine and levobupivacaine with no influence of splice
variant. Levobupivacaine induced a statistically significant depolarizing shift
in the V1/2 activation for aNaV1.5 (mean [SD] from -32 [4.6] mV to -26 [8.1] mV)
but had no effect on the voltage dependence of activation of nNaV1.5. Lidocaine
had no effect on V1/2 activation of either variant but caused a significantly
greater depression of maximum current mediated by nNaV1.5 compared to aNaV1.5.
Similar statistically significant shifts in the V1/2 inactivation (approximately
10 mV) occurred for both LAs and NaV1.5 variants. Levobupivacaine (1 MUM) caused
a significantly greater slowing of recovery from inactivation of both variants
than did lidocaine (10 MUM). Both LAs caused approximately 50% tonic inhibition
of aNaV1.5 or nNaV1.5 when holding at -80 mV. Neither LA caused tonic block at a
holding potential of either -90 or -120 mV, voltages at which there was little
steady-state inactivation. Higher concentrations of either lidocaine (300 MUM) or
levobupivacaine (100 MUM) caused significantly more tonic block at -120 mV.
CONCLUSIONS: These data demonstrate that low concentrations of the LAs exhibit
inactivation-dependent block of NaV1.5, which may provide a rationale for their
use to safely inhibit migration and invasion by metastatic cancer cells without
cardiotoxicity.
PMID- 29958222
TI - Monitoring Depth of Hypnosis: Mid-Latency Auditory Evoked Potentials Derived
aepEX in Children Receiving Desflurane-Remifentanil Anesthesia.
AB - BACKGROUND: The aepEXplus monitoring system, which uses mid-latency auditory
evoked potentials to measure depth of hypnosis, was evaluated in pediatric
patients receiving desflurane-remifentanil anesthesia. METHODS: Seventy-five
patients, 1-18 years of age (stratified for age; 1-3, 3-6, 6-18 years, for
subgroup analyses), were included in this prospective observational study. The
aepEX and the bispectral index (BIS) were recorded simultaneously, the latter
serving as a reference. The ability of the aepEX to detect different levels of
consciousness, defined according to the University of Michigan Sedation Scale,
investigated using prediction probability (Pk), and receiver operating
characteristic (ROC) analysis, served as the primary outcome parameter. As a
secondary outcome parameter, the relationship between end-tidal desflurane and
the aepEX and BIS values were calculated by fitting in a nonlinear regression
model. RESULTS: The Pk values for the aepEX and the BIS were, respectively, .68
(95% CI, 0.53-0.82) and .85 (95% CI, 0.73-0.96; P = .02). The aepEX and the BIS
had an area under the ROC curve of, respectively, 0.89 (95% CI, 0.80-0.95) and
0.76 (95% CI, 0.68-0.84; P = .04). The maximized sensitivity and specificity
were, respectively, 81% (95% CI, 61%-93%) and 86% (95% CI, 74%-94%) for the aepEX
at a cutoff value of >52, and 69% (95% CI, 56%-81%) and 70% (95% CI, 57%-81%) for
the BIS at a cutoff value of >65. The age-corrected end-tidal desflurane
concentration associated with an index value of 50 (EC50) was 0.59 minimum
alveolar concentration (interquartile range: 0.38-0.85) and 0.58 minimum alveolar
concentration (interquartile range: 0.41-0.70) for, respectively, the aepEX and
BIS (P = .69). Age-group analysis showed no evidence of a difference regarding
the area under the ROC curve or EC50. CONCLUSIONS: The aepEX can reliably
differentiate between a conscious and an unconscious state in pediatric patients
receiving desflurane-remifentanil anesthesia.
PMID- 29958223
TI - Can STOP-Bang and Pulse Oximetry Detect and Exclude Obstructive Sleep Apnea?
AB - BACKGROUND: Obstructive sleep apnea (OSA) is related to postoperative
complications and is a common disorder. Most patients with sleep apnea are,
however, undiagnosed, and there is a need for simple screening tools. We aimed to
investigate whether STOP-Bang and oxygen desaturation index can identify subjects
with OSA. METHODS: In this prospective, observational multicenter trial, 449
adult patients referred to a sleep clinic for evaluation of OSA were investigated
with ambulatory polygraphy, including pulse oximetry and the STOP-Bang
questionnaire in 4 Swedish centers. The STOP-Bang score is the sum of 8 positive
answers to Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass
index >35 kg/m, Age >50 years, Neck circumference >40 cm, and male Gender.
RESULTS: The optimal STOP-Bang cutoff score was 6 for moderate and severe sleep
apnea, defined as apnea-hypopnea index (AHI) >=15, and the sensitivity and
specificity for this score were 63% (95% CI, 0.55-0.70) and 69% (95% CI, 0.64
0.75), respectively. A STOP-Bang score of <2 had a probability of 95% (95% CI,
0.92-0.98) to exclude an AHI >15 and a STOP-Bang score of >=6 had a specificity
of 91% (95% CI, 0.87-0.94) for an AHI >15. The items contributing most to the
STOP-Bang were the Bang items. There was a positive correlation between AHI
versus STOP-Bang and between AHI versus oxygen desaturation index, Spearman rho
0.50 (95% CI, 0.43-0.58) and 0.96 (95% CI, 0.94-0.97), respectively. CONCLUSIONS:
STOP-Bang and pulse oximetry can be used to screen for sleep apnea. A STOP-Bang
score of <2 almost excludes moderate and severe OSA, whereas nearly all the
patients with a STOP-Bang score >=6 have OSA. We suggest the addition of nightly
pulse oximetry in patients with a STOP-Bang score of 2-5 when there is a need for
screening for sleep apnea (ie, before surgery).
PMID- 29958224
TI - Impact of Regional Anesthesia on Gastroesophageal Cancer Surgery Outcomes: A
Systematic Review of the Literature.
AB - Regional anesthesia may play a beneficial role in long-term oncological outcomes.
Specifically, it has been suggested that it can prolong recurrence-free survival
and overall survival after gastrointestinal cancer surgery, including gastric and
esophageal cancer, by modulating the immune and inflammatory response. However,
the results from human studies are conflicting. The goal of this systematic
review was to summarize the evidence on the impact of regional anesthesia on
immunomodulation and cancer recurrence after gastric and esophageal surgery. We
conducted a literature search of 5 different databases. Two independent reviewers
analyzed the quality of the selected manuscripts according to prespecified
inclusion and exclusion criteria. Randomized controlled trials were assessed for
potential sources of bias by using the Cochrane Risk of Bias tool. A total of 6
studies were included in the quality analysis and systematic review. A meta
analysis was not conducted for several reasons, including high heterogeneity
among studies, low quality of the reports, and lack of standardized outcomes
definitions. Although the literature suggests that regional anesthesia has some
modulatory effects on the inflammatory and immunological response in the studied
patient population, our systematic review indicates that there is no evidence to
support or refute the use of epidural anesthesia or analgesia with the goal of
reducing cancer recurrence after gastroesophageal cancer surgery.
PMID- 29958225
TI - Remifentanil Stability.
PMID- 29958226
TI - Cervical Spine Motion During Tracheal Intubation Using an Optiscope Versus the
McGrath Videolaryngoscope in Patients With Simulated Cervical Immobilization: A
Prospective Randomized Crossover Study.
AB - BACKGROUND: In patients with an unstable cervical spine, maintenance of cervical
immobilization during tracheal intubation is important. In McGrath
videolaryngoscopic intubation, lifting of the blade to raise the epiglottis is
needed to visualize the glottis, but in patients with an unstable cervical spine,
this can cause cervical spine movement. By contrast, the Optiscope, a rigid video
stylet, does not require raising of the epiglottis during tracheal intubation. We
therefore hypothesized that the Optiscope would produce less cervical spine
movement than the McGrath videolaryngoscope during tracheal intubation. The aim
of this study was to compare the Optiscope with the McGrath videolaryngoscope
with respect to cervical spine motion during intubation in patients with
simulated cervical immobilization. METHODS: The primary outcome of the study was
the extent of cervical spine motion at the occiput-C1, C1-C2, and C2-C5 segments.
In this randomized crossover study, the cervical spine angle was measured before
and during tracheal intubation using either the Optiscope or the McGrath
videolaryngoscope in 21 patients with simulated cervical immobilization. Cervical
spine motion was defined as the change in angle at each cervical segment during
tracheal intubation. RESULTS: There was significantly less cervical spine motion
at the occiput-C1 segment using the Optiscope rather than the McGrath
videolaryngoscope (mean [98.33% CI]: 4.7 degrees [2.4-7.0] vs 10.4 degrees [8.1
12.7]; mean difference [98.33% CI]: -5.7 degrees [-7.5 to -3.9]). There were
also fewer cervical spinal motions at the C1-C2 and C2-C5 segments using the
Optiscope (mean difference versus the McGrath videolaryngoscope [98.33% CI]: -2.4
degrees [-3.7 to -1.2]) and -3.7 degrees [-5.9 to -1.4], respectively).
CONCLUSIONS: The Optiscope produces less cervical spine motion than the McGrath
videolaryngoscope during tracheal intubation of patients with simulated cervical
immobilization.
PMID- 29958227
TI - A Roadmap for Aspiring Surgeon-Scientists in Today's Healthcare Environment.
AB - OBJECTIVE: Surgeon-scientists are an essential component of the field of academic
surgery, contributing to the fundamental understanding of disease and the
discovery of innovative therapies. Despite this recognized value, the current
landscape of academic medicine presents significant barriers to establishing and
maintaining a successful career as a surgeon performing basic/translational
research. Our objective is to define these barriers to academic success for
surgeons, and to provide a consensus strategy for optimizing the chances of
success. SUMMARY BACKGROUND DATA: There is a significant decline in the
proportion of academic surgeons who are pursuing basic science/translational
research, which represents a potential threat to the very identify of the
translational surgeon-scientist. METHODS: Based on published literature and
expert opinion, the Basic Science Committee of the Society of University of
Surgeons prepared this roadmap to encourage and guide the next generation of
surgeon-scientists as they embark on their academic careers. RESULTS: This
roadmap highlights key elements to consider in choosing an initial job and the
importance of identifying a team of committed mentors. Expectations and
guidelines for the first several years in practice are offered. CONCLUSIONS: With
guidance and mentorship, aspiring surgeonscientists can overcome the challenges
inherent in choosing this career path and sustain the important legacy of those
before them.
PMID- 29958228
TI - "Response to Letter to the Editor: Impact of Recurrence Surveillance on
Recurrence Patterns After Resection of Hepatocellular Carcinoma".
PMID- 29958229
TI - Improvement in Liver Transplant Outcomes From Older Donors: A US National
Analysis.
AB - OBJECTIVE: To investigate trends in long-term graft and patient outcomes
following liver transplantation using grafts from donors >=60 years old. SUMMARY
BACKGROUND DATA: The scarcity of donor livers has led to increased utilization of
organs from donors >=60 years old. However, few studies have examined how long
term transplant outcomes from older donors have evolved over time. METHODS: The
OPTN/UNOS database was queried for all first-time isolated adult liver
transplants. We identified 14,796 adult liver transplant using donors ?60-year
old suitable for analysis from 1990 to 2014. Cohorts were then developed based on
5-year intervals of transplant date. Kaplan-Meier analysis was used to compare
graft and patient survival for recipients from older donor across each 5-year
era. RESULTS: Utilization of donor grafts >=60 years old increased steadily for
the first 15 years of the study, but has leveled off over the last 10 years.
Comparison of the earliest and latest eras in the study was notable for an
increase in median recipient age (51 vs. 59, P < 0.001) and reduction in median
cold ischemic time (10 vs. 6 h, P = 0.001). Unadjusted 5-year graft and patient
survival has improved significantly over time (P < 0.0001). More importantly, the
discrepancy in survival between older and younger grafts has narrowed
substantially over time (P < 0.0001). CONCLUSIONS: This study demonstrates
significant improvement in transplant outcomes with donor grafts >=60-years old
and supports increased but judicious use of extended criteria donors liver
grafts. Improved patient selection and reduction in cold ischemia time appear to
be contributing factors.
PMID- 29958230
TI - Comparing Preventive Strategies for Acute Kidney Injury After Major Surgery:
Study Design Is Important.
PMID- 29958231
TI - Splenectomy in Total Gastrectomy for Advanced Proximal Gastric Carcinoma.
PMID- 29958232
TI - Stand Tall-A Virtual Translation of the Otago Exercise Program.
AB - BACKGROUND AND PURPOSE: The Otago Exercise Program (OEP) is effective at
preventing falls and fall-related injuries. The resources and personnel required
for program delivery and challenges inherent in monitoring participant adherence
and compliance pose significant barriers to increasing the number of older adults
participating in the OEP. Alternative delivery systems using virtual platforms
may pose a solution. The purposes of this article were to (1) describe the "Stand
Tall" intervention, a virtual translation of the OEP; (2) describe Stand Tall
participant characteristics and fall-related risk at baseline; and (3) identify
changes in physical performance measures associated with fall risk from baseline
to 8-week follow-up. METHODS: This was a quasi-experimental, single-group,
pretest-posttest design. Forty-two older adults at risk for falls were recruited.
Participants were oriented to Stand Tall by study personnel and then monitored
and progressed virtually with face to face check-ins. Participants independently
logged in and completed a prescribed a set of exercises 3 times a week for 30
minutes for a total of 8 weeks. RESULTS AND DISCUSSION: The average participant
age was 75.0 (9.1) years and self-reported 2.3 (1.7) chronic conditions. There
were more men than women (52.4%) in the study. Participants were primarily non
Hispanic white (90.5%), had a college education (61.9), 40% reported falling in
the past 6 months, and 60% screened positive for mild cognitive impairment.
Participants were beginning to show decline in function with average single-leg
stance less than 10 seconds and 30-second chair rise scores below normative
values. Participants demonstrated high adherence rates (>88%) and significant
improvements in physical performance measures associated with fall risk. These
results may be limited to a less frail population and the study was not powered
to demonstrate a reduction in falls. CONCLUSIONS: Results support that an avatar
delivered version of the OEP is effective, feasible, viable, and enjoyable for
community-dwelling older adults. These types of platforms should be considered as
potential mechanisms to increase availability of fall prevention programs.
PMID- 29958233
TI - Nondipping pattern on 24-h ambulatory blood pressure monitoring is associated
with left ventricular hypertrophy in chronic kidney disease.
AB - BACKGROUND: Few studies have assessed the role of 24-h ambulatory blood pressure
monitoring (ABPM) in adults with nondialysis chronic kidney disease (CKD). We
examined the potential determinants of left ventricular hypertrophy (LVH) and
mass index (LVMI) in this population. PARTICIPANTS AND METHODS: We carried out a
cross-sectional study on 69 stage 3b-5 CKD adults who had ABPM and transthoracic
echocardiography performed simultaneously. Hypertension (HT) was defined as 24 h
blood pressure (BP) of at least 130/80 mmHg. ABPM parameters considered were BP
dipping status, BP load, and the BP night-time/daytime ratio. We performed
stepwise backward multivariate linear and logistic regression to assess the
determinants of LVH and LVMI. ABPM parameters were considered the main
independent variables, whereas HT, angiotensin-converting enzyme
inhibitor/angiotensin II receptor antagonist use, glomerular filtration rate of
less than 30 ml/min/1.72 m, diabetes, smoking, age, sex, hemoglobin, and
parathyroid hormone levels were considered covariates. RESULTS: LVH was present
in 22 (31.8%) patients. In linear regression analysis, systolic [beta=-13.8, 95%
confidence interval (CI)=-26.3 to -1.3, P=0.031] and mean (beta=-13.5, 95% CI=
25.7 to -1.2, P=0.031) nondipping status was associated with increased LVMI. BP
load and night-time/daytime ABPM ratio were not associated with LVMI. In logistic
regression analysis, systolic nondipping status (odds ratio=0.27, 95% CI=0.08
0.91, P=0.036) was associated with LVH. Among covariates, estimated glomerular
filtration rate of less than 30 ml/min/1.72 m and HT were associated with LVH and
increased LVMI. At 1-year follow-up, mean nondipping status on the initial ABPM
remained associated significantly with increased LVMI (beta=-19.8, 95% CI=-36.6
to -3.0, P=0.022). CONCLUSION: These data confirm the high incidence of LVH among
nonrenal replacement therapy CKD patients and suggest that the nondipping
phenomenon on ABPM is associated independently with LVH and increased LVMI in
this population.
PMID- 29958234
TI - Management of Anterior Cruciate Ligament Injuries in Adults Aged >40 Years.
AB - Management of anterior cruciate ligament (ACL) injuries in adults aged >40 years
has received increased attention in the literature because of an increase in the
functional demands of aging athletes. Multiple structural and biomechanical age
dependent changes exist in the ACL, for example, fewer mesenchymal stem cells,
decreased healing potential, decreased structural organization, decreased
stiffness, and a decreased load to failure with age. As in younger patients, ACL
insufficiency can predispose an older patient to the same risks of recurrent
instability, meniscal and chondral injury, and osteoarthritis. The role of
nonsurgical versus surgical management in these patients remains controversial.
Lower-demand patients may be able to cope with ACL deficiency. Higher-demand
patients may have functional instability, and the limited studies available
suggest good functional outcomes with surgical reconstruction of the ACL in this
population.
PMID- 29958235
TI - Cancer Antigen 125 Levels are Significantly Associated With Prognostic Parameters
in Uterine Papillary Serous Carcinoma.
AB - OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a highly aggressive
subtype of endometrial carcinoma. Histopathologically, it resembles the pattern
of serous papillary carcinoma of the ovary. Cancer antigen 125 (CA-125) is the
most widely used biomarker in epithelial ovarian carcinoma. Its use in UPSC
evaluation has yet to be determined. The purpose of this study was to investigate
the significance of preoperative serum CA-125 as a prognostic factor in patients
with UPSC. METHODS: The study cohort included all women with UPSC operated in our
institution between January 2002 and June 2016. All patients underwent complete
surgical staging. Preoperative CA-125 was reviewed and correlated with clinical
and pathological parameters. RESULTS: Sixty-one women met the study criteria.
Median preoperative CA-125 was found to be significantly associated with disease
stage. Patients with disease stages I to IV had median preoperative CA-125 levels
of 12.15, 19.6, 22.6, and 177.5 U/mL (P < 0.0001) respectively. Levels of CA-125
were significantly associated with positive cytology (P < 0.0001), omental
disease (P < 0.0001), pelvic or para-aortic lymph node metastasis (P < 0.0001),
and adnexal involvement (P < 0.0001). The optimal cutoff that provided the best
sensitivity and specificity for omental and parametrial involvement as well as
positive cytology was 57.5 U/mL. For adnexal and lymph node involvement, the
optimal cutoff value was 41.8 U/mL. CONCLUSIONS: In patients with UPSC,
preoperative CA-125 level correlates with known prognostic parameters of
endometrial carcinoma and is associated with extrauterine involvement. These data
should stimulate the need for further evaluation of the role of CA-125 in
predicting recurrence and survival in UPSC.
PMID- 29958236
TI - ESGO Survey on Current Practice in the Management of Cervical Cancer.
AB - OBJECTIVE: The aim of this survey was to acquire an overview of the current
management of cervical cancer with an emphasis on the early disease stages.
MATERIALS AND METHODS: A hyperlink to the survey was sent to the European Society
of Gynaecological Oncology Office database. The survey contained 6 groups of
questions regarding the characteristics of respondents, pretreatment workup,
management of the early stages of cervical cancer, adjuvant treatment, fertility
sparing treatment, and surveillance. RESULTS: In total, 566 responses were
collected. The most frequent imaging method used in the workup was magnetic
resonance imaging (74%), followed by computed tomography (54%) and positron
emission tomography/computed tomography (25%). Conization or simple hysterectomy
was a preferred procedure in stage T1a1 lymphovascular space invasion (LVSI)
positive for 79% of respondents, in stage T1a2 LVSI-negative for 58%, and in
stage T1a2 LVSI-positive for 28%. Sentinel lymph node biopsy alone was reported
in stage T1a1 by 17% and in stage T1b1 less than 2 cm by 9%, whereas systematic
lymphadenectomy by 29% and 90% of respondents. Macrometastases, micrometastases,
and isolated tumor cells in lymph nodes were considered indications for adjuvant
treatment by 96%, 93%, and 68% of respondents, respectively. Neoadjuvant
chemotherapy was reported by 28% and 19% of respondents in fertility-sparing and
nonsparing management in stage T1b1. Over 60% of respondents recommend primary
surgery for their patients with T1b2 N0 disease and 81% of them use a combination
of adverse prognostic factors as indication for adjuvant radiotherapy in pN0
disease. CONCLUSIONS: The results of this survey indicate considerable
differences in the workup and treatment of cervical cancer in current clinical
practice.
PMID- 29958237
TI - A prospective study of adverse effects of antipsychotics in adolescents with
schizophrenia during a 6-month follow-up.
AB - There is a paucity of follow-up studies of neurological, endocrine, and metabolic
adverse effects of antipsychotics in adolescents from low-income and middle
income countries, who have a higher prevalence of obesity and overweight, and
could present increased morbidity. A Mexican sample of 86 adolescents with
schizophrenia was examined during a 6-month follow-up using the Simpson-Angus,
abnormal involuntary movement and Barnes Akathisia rating scales, in addition to
a side effects score sheet and other laboratory measures. Binary logistic
regression models were used to identify specific variables as predictors of
weight gain. Sleep difficulties, restlessness, drowsiness, changes in thyroid
hormones, and a linear increase in weight gain were observed. A baseline positive
and negative syndrome scale score greater than 97 predicted a 5 kg increase at
month 3 (odds ratio: 4.52, 95% confidence interval: 1.5-13.2). The absence of a
plateau in weight gain in the present study across the 6-month treatment period
and its relationship with illness severity suggests that even longer follow-up
time should be examined in future studies in these patient populations.
PMID- 29958238
TI - The effect of methylphenidate treatment on psychopathic behavior of patients
having attention-deficit hyperactivity disorder with and without oppositional
defiant disorder.
AB - To evaluate the effect of 3 months of methylphenidate (MPH) treatment on
psychopathic behavior in children having attention-deficit hyperactivity disorder
(ADHD) with and without comorbid oppositional defiant disorder (ODD). Twenty
seven children with Diagnostic and Statistical Manual of Mental Disorders, fifth
ed., ADHD (13 female/14 male; aged 13.3+/-2.2 years old) were compared to an
age/sex matched ADHD/ODD group (N=27, eight female/19 male; aged 11.8+/-1.9
years). The attention-deficit hyperactivity disorder rating scale (ADHD-RS) and
the California Child Q-Set (CCQ) were used in both groups before MPH treatment
(0.8-1.2 mg/kg/day) and 3 months thereafter. Significant reduction in the ADHD-RS
scores was detected following MPH treatment in both the ADHD/ODD group and in the
ADHD group (P<0.0011 and P=0.0012, respectively). Reduction in the CCQ scores was
obtained in the ADHD/ODD group (P=0.0001) but not in in the ADHD group (P=0.18).
A correlation was found between the reductions in the ADHD-RS and CCQ scores
following MPH treatment in the ADHD/ODD group (Spearman's r=0.43, P=0.024). MPH
treatment in children with ADHD/ODD was associated with reduction in psychopathic
scores, and the reduction correlated with a corresponding improvement in their
ADHD severity.
PMID- 29958239
TI - Acceptance: A Letter to My Grieving Self.
PMID- 29958240
TI - Early Hemodynamic Management of Critically Ill Burn Patients.
PMID- 29958241
TI - A Comparison of Outcomes of Trauma Patients with Ventilator- Associated Events by
Diagnostic Criteria Set.
AB - BACKGROUND: The Centers for Disease Control and Prevention replaced the
definition for ventilator-associated pneumonia with an algorithm comprised of
three categories-ventilator associated condition (VAC), infection -related
ventilator associated complication (IVAC) and possible ventilator associated
pneumonia (PVAP). We sought to compare the outcome of trauma patients with VAEs
to those with No VAEs. METHODS: Patients admitted from 2013-2017 were identified
from trauma registry. Logistic regression was performed for the association
between VAEs and mortality. RESULTS: 2680 patients were admitted to our trauma
center, 2290 had no VAE, 100 had VACs, 85 had IVACs, and 205 had PVAPs. Adjusted
for race, sex, blunt injury mechanisms, and Injury Severity Score, all VAEs had a
longer hospital length of stay, ICU stay, and days of ventilator support when
compared to those with no VAE (all p < 0.0001). Nosocomial complication rates
were not different by VAE group. Compared to patients with no VAE, an over two
fold increased mortality odds was observed for VAC (OR 2.39, 95% CI 1.50-3.80)
and IVAC patients (OR 2.07, 95% CI 1.23-3.47), and a 50% mortality increased was
observed for PVAP patients (OR 1.46, 95% CI 1.00-2.12). These associations became
similar with an approximate 2.5-fold increased mortality odds among patients with
at least one week on ventilator support. CONCLUSION: VAEs increase the odds of
mortality, particularly for patients with VACs and IVACs. Among patients on
ventilator support for at least a week, the associations are similar among VAE
types, suggesting no single VAE type is more severe than others.
PMID- 29958242
TI - The Lncrna, H19 Mediates the Protective Effect of Hypoxia Postconditioning
Against Hypoxia-Reoxygenation Injury to Senescent Cardiomyocytes by Targeting
MicroRNA-29b-3p.
AB - BACKGROUND: Ischemic postconditioning (I/Post) is an endogenous protection
mechanism that reduces injury induced by ischemia-reperfusion (I/R). It remains
controversial whether I/Post protects against I/R injury to the aging heart. The
long non-coding RNA, H19 protects H9c2 cells against hypoxia-induced injury. This
study aimed to elucidate the role of H19 in the hypoxic postconditioning (H/Post)
of aged cardiomyocytes. METHODS: Senescence induced by D-galactose in primary
cardiomyocytes from neonatal Sprague-Dawley rats was measured by senescence
associated beta-galactosidase staining. Hypoxic injury was evaluated by cell
viability and apoptosis assays. H19 expression before and after hypoxia
reoxygenation (H/R) and H/Post was evaluated by real-time polymerase chain
reactions. miR-29b-3p-binding sites in H19 and the cellular inhibitor of
apoptosis protein 1 (cIAP1) were predicted by bioinformatics analysis, and
interaction was verified by luciferase assay. The effects of altered H19, miR-29b
3p and cIAP1 expression on the viability and apoptosis of senescent
cardiomyocytes following H/Post were determined. RESULTS: H/Post prevented H/R
injury in normal but not senescent cardiomyocytes. H19 expression was remarkably
down-regulated after H/Post in senescent compared with normal cardiomyocytes.
Small interfering RNA-mediated knockdown of H19 in senescent cardiomyocytes
increased H/Post-induced injury. miR-29b-3p was regulated by H19 and led to a
greater injury. miR-29b-3p directly targeted the 3'-untranslated region of cIAP1
and suppressed its expression. Furthermore, knockdown of cIAP1 damaged senescent
cardiomyocytes following H/Post. CONCLUSIONS: These findings suggest that H19
mediated the antiapoptotic effect of H/Post against H/R-induced injury to aged
cardiomyocytes by inhibiting miR-29b-3p expression.
PMID- 29958243
TI - The organization of Danish emergency departments.
AB - INTRODUCTION: Twenty-one new Danish emergency departments (EDs) were established
following a 2007 policy reform that included ED autonomy to self-organize. The
aim of this study was to describe the organization of the 21 departments and
their organizational challenges. PARTICIPANTS AND METHODS: We used a qualitative
design based on COREQ guidelines. All 21 EDs participated, and 123 semi
structured interviews with hospital and ED leaders, physicians, nurses, and
secretaries were performed between 2013 and 2015. We used the framework matrix
method to investigate the ED goals, setting, structure, staff, task coordination,
and incentive structure. RESULTS: We identified three generic models (virtual,
hybrid, and independent). All had goals of high quality of care and high
efficiency. The virtual model was staffed by junior physicians and tasks were
coordinated by other departments. The hybrid model was staffed by junior
physicians and senior physicians according to other departments and the ED. The
ED coordinated all activities. The independent model was staffed by junior
physicians and senior physicians, and activities were coordinated by the ED. Of
the EDs, 19 utilized different organizational models at different times during a
24-h period and on weekdays and weekends. The main challenge of the virtual and
hybrid models was high dependency on other departments. The main challenge of the
independent model was establishing a high level of quality of emergency medicine.
DISCUSSION AND CONCLUSION: We identified three organizational ED models (virtual,
hybrid, and independent). Nineteen EDs used more than one organizational model
depending on the time of day or day of the week.
PMID- 29958244
TI - The late positive potential and subjective arousal ratings evoked by negative
images vary as a function of oxytocin receptor genotype SNP rs53576.
AB - In the central nervous system the neuropeptide oxytocin mediates a range of
behaviors related primarily to emotionality. One factor that influences
oxytocinergic communication in the human brain and correlates with emotional
behaviors is the single nucleotide polymorphism rs53576 on the oxytocin receptor
gene (OXTR). For example, variations in this OXTR genotype are related to
parental, altruistic, and other prosocial behaviors. Electroencephalographic
waveforms of visually evoked response potentials recorded at the midline parietal
electrode site display a prominent component putatively involved with attention
allocation called the late positive potential. The magnitude of the late positive
potential was found to be significantly higher in homozygous G allele individuals
compared with A allele carriers when viewing negative emotionally charged images.
Inversely, A allele carriers rated these negative images as more arousing, when
measured by the Self-Assessment Manikin rating scale. These data suggest that
OXTR functioning contributes to visual processing and subjective experience of
negative stimuli.
PMID- 29958245
TI - Gentiopicroside protects neurons from astrocyte-mediated inflammatory injuries by
inhibition of nuclear factor-kappaB and mitogen-activated protein kinase
signaling pathways.
AB - The effects of gentiopicroside (Gent), an active component derived from the
traditional Chinese medicine Gentiana macrophylla, on lipopolysaccharide-induced
astrocyte activation and subsequent neuronal damage were investigated. Gent
significantly inhibited the release of tumor necrosis factor-alpha, interleukin
1beta, nitric oxide, and prostaglandin E, as well as expressions of inducible
nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-induced primary
astrocytes. Furthermore, Gent relieved neurotoxicity from astrocyte-mediated
inflammatory injury. Mechanism studies indicated that Gent significantly
suppressed nuclear factor-kappaB nuclear translocation and down-regulated c-Jun-N
terminal kinase/stress-activated protein kinase mitogen-activated protein kinase
phosphorylation levels with little influence on elevated p-p38 levels. Taken
together, our findings suggested Gent could prevent the neurotoxicity related to
astrocyte-mediated inflammatory injury by inhibition of nuclear factor-kappaB and
mitogen-activated protein kinase signaling pathways. The study also indicated
that neuronal injury could be prevented by promptly modulating inflammatory
responses of astrocytes.
PMID- 29958246
TI - The poverty of theory: Evidence-based medicine and the social contract.
PMID- 29958247
TI - Plasma coadministration improves resuscitation with tranexamic acid or
prothrombin complex in a porcine hemorrhagic shock model.
AB - BACKGROUND: Traumatic coagulopathy has now been well characterized and carries
high rates of mortality owing to bleeding. A 'factor-based' resuscitation
strategy using procoagulant drugs and factor concentrates in lieu of plasma is
being used by some, but with little evidentiary support. We sought to evaluate
and compare resuscitation strategies using combinations of tranexamic acid (TXA),
prothrombin complex concentrate (PCC), and fresh frozen plasma (FFP). METHODS:
Sixty adult swine underwent 35% blood volume hemorrhage combined with a truncal
ischemia-reperfusion injury to produce uniform shock and coagulopathy. Animals
were randomized to control (n = 12), a single-agent group (TXA, n = 10; PCC, n =
8; or FFP, n = 6) or combination groups (TXA-FFP, n = 10; PCC-FFP, n = 8; TXA
PCC, n = 6). Resuscitation was continued to 6 hours. Key outcomes included
hemodynamics, laboratory values, and rotational thromboelastometry. Results were
compared between all groups, with additional comparisons between FFP and non-FFP
groups. RESULTS: All 60 animals survived to 6 hours. Shock was seen in all
animals, with hypotension (mean arterial pressure, 44 mm Hg), tachycardia (heart
rate, 145), acidosis (pH 7.18; lactate, 11), anemia (hematocrit, 17), and
coagulopathy (fibrinogen, 107). There were clear differences between groups for
mean pH (p = 0.02), international normalized ratio (p < 0.01), clotting time (CT;
p < 0.01), lactate (p = 0.01), creatinine (p < 0.01), and fibrinogen (p = 0.02).
Fresh frozen plasma groups had significantly improved resuscitation and clotting
parameters (Figures), with lower lactate at 6.5 versus 8.4 (p = 0.04), and
increased fibrinogen at 126 versus 95 (p < 0.01). Rotational thromboelastometry
also demonstrated shortened CT at 60 seconds in the FFP group vs 65 seconds in
the non-FFP group (p = 0.04). CONCLUSION: When used to correct traumatic
coagulopathy, combinations of FFP with TXA or PCC were superior in improving
acidosis, coagulopathy, and CT than when these agents are given alone or in
combination without plasma. Further validation of pure factor-based strategies is
needed.
PMID- 29958248
TI - The combined utility of extended focused assessment with sonography for trauma
and chest x-ray in blunt thoracic trauma.
AB - BACKGROUND: Portable chest x-ray (CXR) and extended focused assessment with
sonography for trauma (EFAST) screen patients for thoracic injury in the trauma
bay. It is unclear if one test alone is sufficient, if both are required, or if
the two investigations are complementary. Study objectives were to define the
combined diagnostic yield of EFAST and CXR among stable blunt thoracic trauma
patients and to determine if a normal EFAST and CXR might obviate the need for
computed tomography (CT) scan of the chest. METHODS: All blunt trauma patients 15
years or older presenting to LAC+USC Medical Center in 2016 were screened. Only
patients who underwent CT thorax were included. Patients were excluded if they
presented more than 24 hours after injury, were transferred, or if they did not
undergo EFAST and CXR. Demographics, physical examination (PEx) of the thorax,
injury data, investigations, procedures, and outcomes were collected. The EFAST,
CXR, and PEx findings were compared to the gold standard CT thorax to calculate
the diagnostic yield of each investigation and combinations thereof in the
assessment for clinically significant thoracic injury. RESULTS: One thousand
three hundred eleven patients met inclusion/exclusion criteria. Most common
mechanisms of injury were motor vehicle collision (n = 385, 29%) and auto versus
pedestrian trauma (n = 379, 29%). Mean Injury Severity Score was 11 (1-75), with
mean Abbreviated Injury Scale chest score of 1.6 (1-6). The sensitivities of
EFAST, CXR, and PEx, either individually or in combination, were less than 0.73
in the detection of clinically significant thoracic injury. The most common
missed clinically significant injuries were sternal fractures, scapular
fractures, clavicular fractures, and pneumothoraces. Motorcycle collisions and
auto versus pedestrian traumas resulted in the highest rates of missed injury.
CONCLUSION: Even in conjunction with the physical examination, the sensitivity of
EFAST+CXR in the detection of clinically significant thoracic injury is low.
Therefore, if clinical suspicion for injury exists after blunt thoracic trauma, a
normal EFAST+CXR is insufficient to exclude injury and CT scan of the chest
should be performed. LEVEL OF EVIDENCE: Diagnostic tests/criteria, level III.
PMID- 29958250
TI - Featured Articles for CME Credit July 2018.
PMID- 29958249
TI - Health care utilization and the cost of posttraumatic acute respiratory distress
syndrome care.
AB - BACKGROUND: Posttraumatic acute respiratory distress syndrome (ARDS) is
associated with prolonged mechanical ventilation and longer hospitalizations. The
relationship between posttraumatic ARDS severity and financial burden has not
been previously studied. We hypothesized that increasing ARDS severity is
associated with incrementally higher health care costs. METHODS: Adults arriving
as the highest level of trauma activation were enrolled in an ongoing prospective
cohort study. Patients who survived 6 hours or longer are included in the
analysis. Blinded review of chest radiographs was performed by two independent
physicians for any intubated patient with PaO2:FIO2 ratio of 300 mmHg or lower
during the first 8 days of admission. The severity of ARDS was classified by the
Berlin criteria. Hospital charge data were used to perform standard costing
analysis. RESULTS: Acute respiratory distress syndrome occurred in 13% (203 of
1,586). The distribution of disease severity was 33% mild, 42% moderate, and 25%
severe. Patients with ARDS were older (41 years vs. 35 years, p < 0.01), had
higher median Injury Severity Score (30 vs. 10, p < 0.01), more chest injury
(Abbreviated Injury Scale score, >= 3: 51% vs. 21%, p < 0.01), and blunt
mechanisms (85% vs. 53%, p < 0.01). By ARDS severity, there was no significant
difference in age, mechanism, or rate of traumatic brain injury. Increasing ARDS
severity was associated with higher Injury Severity Score and higher mortality
rates. Standardized total hospital charges were fourfold higher for patients who
developed ARDS compared with those who did not develop ARDS (US $434,000 vs. US
$96,000; p < 0.01). Furthermore, the daily hospital charges significantly
increased across categories of worsening ARDS severity (mild, US $20,451;
moderate, US $23,994; severe, US $33,316; p < 0.01). CONCLUSION: The development
of posttraumatic ARDS is associated with higher health care costs. Among trauma
patients who develop ARDS, total hospital charges per day increase with worsening
severity of disease. Prevention, early recognition, and treatment of ARDS after
trauma are potentially important objectives for efforts to control health care
costs in this population. LEVEL OF EVIDENCE: Economic and value-based
evaluations, level IV.
PMID- 29958252
TI - Joint Statement by the Surgery Journal Editors Group.
PMID- 29958253
TI - Diagnostic Algorithm for Cholesteryl Ester Storage Disease: Clinical Presentation
in 19 Polish Patients.
AB - BACKGROUND: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal
recessive lysosomal lipid storage disorder that results in an early-onset,
severe, and lethal phenotype, known as Wolman disease, or a late-onset,
attenuated phenotype, cholesteryl ester storage disease (CESD). The aim of our
study was to describe the clinical presentation of CESD, focusing on the first
noted abnormalities in patients. A diagnostic algorithm of CESD was also
proposed. METHODS: This is an observational, 1-center study of 19 Polish patients
with late-onset LAL-D. RESULTS: The mean age at which the first symptoms were
reported was 4 years and 6 months. A mild hepatomegaly was the most common
initial abnormality observed in all (100%) patients. Seven (37%) patients were
noted to have mildly to moderately elevated serum transaminases. At the time of
first hospitalization all (100%) patients presented with hepatomegaly, 15 (79%)
patients presented with elevated serum transaminases and all (100%) patients had
dyslipidemia. The mean age at the time of CESD diagnosis was 7 years and 2
months. Diagnoses were based on a deficient LAL activity in leukocytes (in all
patients) and the LIPA gene mutations (in 47% of them). All the patients were
carriers for the mutation c.894G>A in the LIPA gene. There was approximately a 3
year delay from initial symptoms to final diagnosis. CONCLUSIONS: Hepatomegaly
constitutes the most common presenting clinical sign of CESD. Hepatomegaly and
dyslipidemia defined as elevated serum total and LDL cholesterol, elevated
triglycerides and normal to low HDL cholesterol, comprises the most
characteristic findings at CESD diagnosis.
PMID- 29958254
TI - Indications for Helicobacter pylori Eradication: Do We Need to Consider to Screen
and Treat Asymptomatic Children?
PMID- 29958255
TI - Compounding Isn't Just for Pharmacists.
PMID- 29958257
TI - 2017 INS Financial Report.
PMID- 29958256
TI - State of the Society.
PMID- 29958258
TI - Presidential Address.
PMID- 29958259
TI - Cancer and the Broken Heart: Complications and Implications of Therapy-Related
Cardiotoxicity.
AB - The growing number of adult long-term cancer survivors has expanded our knowledge
of negative physiologic sequelae associated with curative therapies. Of note are
the cardiovascular corollaries of chest radiotherapy and some commonly used
chemotherapy agents. A contemporary understanding of risk factors has facilitated
the development of guidelines for prevention and surveillance of cardiac
compromise. The future holds promise with enhanced opportunities to use
cardioprotectant drugs and biomarkers to prevent and detect early myocardial
changes. Infusion therapy nurses must keep abreast of these developments to
facilitate their roles as patient educators and advocates in the face of this
toxicity's prevalence.
PMID- 29958260
TI - Addressing Administration Challenges Associated With Blinatumomab Infusions: A
Multidisciplinary Approach.
AB - Blinatumomab has shown great potential for patients with chemotherapy-resistant B
cell acute lymphocytic leukemia. Blinatumomab's toxicity profile includes central
nervous system toxicities, as well as cytokine release syndrome. Although
neurological toxicities associated with blinatumomab are almost always
reversible, early detection and intervention of these toxicities is vital to
ensure that patients continue their full course of treatment. Guidelines for the
preparation and administration of blinatumomab in both inpatient and outpatient
settings, as well as a standardized neurological nursing assessment, were
developed to ensure safe and effective administration of blinatumomab.
PMID- 29958261
TI - Peripheral Infiltration and Extravasation Injury Methodology: A Retrospective
Study.
AB - Peripheral infiltration is defined as the inadvertent delivery of nonvesicant
fluid or medication into surrounding tissue that has the potential to harm the
patient. Vesicant fluid that has leaked into the tissue space is called
extravasation. At present, there is no agreement in the literature on the best
practice for managing these injuries in pediatric patients. The purpose of this
study was to identify occurrences of peripheral infiltration injuries and examine
treatment modalities used to treat pediatric patients who suffered such an
injury.
PMID- 29958262
TI - Evaluating the Efficacy and Use of Vein Visualization Equipment Among Clinical
Nurses in an Intermediate Care Environment.
AB - This study compared traditional short peripheral catheter (SPC) insertion methods
with 2 vein visualization equipment models among a general patient population on
a surgical step-down unit based on first-attempt success rates and the time
required to achieve catheter insertion. The experiences of clinical nurses using
the ultrasound and vein visualization equipment were also explored. No
significant statistical differences were found between the insertion methods,
based on 90 unique SPC insertion attempts. However, nurses reported that using
the vein visualization equipment informed patient care, facilitated communication
among members of the health care team, and facilitated second SPC insertion
attempts. Nursing staff also used the equipment more often after the study
concluded.
PMID- 29958263
TI - Phlebitis Signs and Symptoms With Peripheral Intravenous Catheters: Incidence and
Correlation Study.
AB - This study was undertaken to calculate the incidence of 8 signs and symptoms used
for the diagnosis of phlebitis with peripheral intravenous catheters, or short
peripheral catheters, and the level of correlation between them. A total of 22
789 daily observations of 6 signs (swelling, erythema, leakage, palpable venous
cord, purulent discharge, and warmth) and 2 symptoms (pain and tenderness) were
analyzed of 5907 catheter insertion sites. Most signs and symptoms of phlebitis
occurred only occasionally or rarely; the incidence of tenderness was highest
(5.7%). Correlations were mostly low; warmth correlated strongly with tenderness,
swelling, and erythema.
PMID- 29958264
TI - Effect of Repeated Freeze-Thaw on Serum Biomarkers Associated with Eye Disease.
AB - BACKGROUND Serum biomarkers are associated with eye diseases, which results in
the need for cryopreservation of serum samples. However, the effect on serum
biomarker levels of repeatedly freezing and thawing remains poorly understood.
The aim of this study was to evaluate the effects of repeated freeze-thaw on the
serum levels of the protein, complement C3c (C3c), the micromolecule, uric acid
(UA), and the enzyme, angiotensin-converting enzyme (ACE). MATERIAL AND METHODS
Serum samples were obtained from 50 patients who attended an ophthalmic
outpatient department. Following baseline measurements, the serum samples from
each subject were divided into aliquots and stored at -80 degrees C for further
analysis, following between one to six freeze-thaw cycles. The serum levels of
C3c, UA, and ACE were measured immediately after the stored serum samples were
thawed. RESULTS The serum level of C3c was significantly changed after the first
freeze-thaw cycle (p<0.05), and a significant alteration in serum ACE levels
occurred after the third freeze-thaw cycle (p<0.05). The serum UA level remained
unchanged after all freeze-thaw cycles. Repeated freeze-thaw cycles significantly
increased the serum levels of C3c and decreased the serum levels of ACE. The
serum levels of C3c, UA, and ACE, respectively were significantly correlated
(p<0.001), while the correlation coefficient for C3c and UA were improved when
compared with ACE. CONCLUSIONS Repeated freeze-thaw can have variable effects on
the serum levels of biomarkers, C3c, UA and ACE, which supports the need for
quality control of cryopreserved serum for biomarker evaluation.
PMID- 29958265
TI - Carbapenemase-producing Klebsiella pneumoniae in Peru: Is there a need for
further phenotypic and genotypic testing?
PMID- 29958266
TI - Is platelet-rich plasma effective for osteoarthritis?
AB - INTRODUCTION: Despite varied non-surgical alternatives for the treatment of
osteoarthritis, many patients remain symptomatic. In the last decade, the use of
intra-articular platelet-rich plasma (PRP) has been proposed as an option.
However, there is controversy about its clinical benefit and safety. METHODS: To
answer this question we used Epistemonikos, the largest database of systematic
reviews in health, which is maintained by screening multiple information sources,
including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the
systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis
and generated a summary of findings table using the GRADE approach. CONCLUSIONS:
We identified twelve systematic reviews including four studies overall, of which
all corresponded to randomized trials. We concluded that intra-articular
injection of platelet-rich plasma might slightly decrease joint pain and improve
patient satisfaction,vut it is not clear whether it has any effect on
functionality because the certainty of the evidence is very low. As for the
adverse effects, if they exist, they would be non-severe and self-limited.
PMID- 29958267
TI - Cost-effectiveness of lenalidomide in combination with dexamethasone compared to
bortezomib in combination with dexamethasone for the second-line treatment of
multiple myeloma in Chile.
AB - BACKGROUND: Multiple myeloma is a hematologic malignancy affecting bone marrow
derived plasma cells. Current therapies are not able to eradicate the disease and
most patients become refractory to the treatment. Lenalidomide and bortezomib
have proved effective in the second-line treatment of these patients. OBJECTIVE:
To evaluate the cost-effectiveness of lenalidomide in combination with
dexamethasone compared to bortezomib in combination with dexamethasone in
patients with multiple myeloma previously treated with bortezomib, from the
perspective of the Chilean National Health Service. METHODOLOGY: A four-state
Markov model (preprogression on treatment; preprogression off treatment,
progression and death) was used to simulate the evolution of a cohort of multiple
myeloma patients over a 25-year time horizon. Efficacy data, resource use and
frequency of adverse events were extracted from MM009/010 studies and a
retrospective analysis of retreatment with bortezomib. All inputs were validated
by experts. A 3% annual discount rate was used for costs and health outcomes. The
robustness of the results was evaluated through univariate and probabilistic
sensitivity analyses. RESULTS: Lenalidomide in combination with dexamethasone
treatment provided 1.41 incremental life years and 0.83 incremental quality
adjusted life years in comparison with bortezomib in combination with
dexamethasone, with an incremental cost of 11 864 597.86 CLP (19 589.86 US$). The
incremental cost-effectiveness and cost-utility ratio were estimated at 8 410
266.92 CLP (13 886,35 US$) / incremental life year and 14 271 896.16 CLP (23
564,59 US$)/incremental quality-adjusted life years, respectively. CONCLUSIONS:
Lenalidomide in combination with dexamethasone represents a potentially cost
effective alternative for the second-line treatment of patients with multiple
myeloma who are not eligible for transplantation, from the perspective of the
Chilean National Health Service.
PMID- 29958268
TI - Validity and reliability of the Beck Depression Inventory (BDI-II) in general and
hospital population of Dominican Republic.
AB - The Beck Depression Inventory-II (BDI-II) is currently one of the most widely
used measures in both research and clinical practice for assessing depression.
Although the psychometric properties of the scale have been well established
through many studies worldwide, so far there is no study examining the validity
and reliability of BDI-II in Republic Dominican. The purpose of the present study
was twofold: (a) to examine the latent structure of BDI-II by testing several
competing models proposed in the literature; and (b) to provide evidence of
validity and reliability of the BDI-II in Republic Dominican. Confirmatory factor
analysis indicated that a bifactor model with a general depression factor and
three specific factors consisting of cognitive, affective and somatic showed the
best fit to the data. Internal reliability was moderate to high for all subscales
and for the total scale. Scores on BDI-II discriminated between clinical and
general population, supporting for external validity. Practical implications are
discussed and suggestions for further research are also made.
PMID- 29958269
TI - The psycholinguistic and affective structure of words conveying pain.
AB - Despite the flourishing research on the relationships between affect and
language, the characteristics of pain-related words, a specific type of negative
words, have never been systematically investigated from a psycholinguistic and
emotional perspective, despite their psychological relevance. This study offers
psycholinguistic, affective, and pain-related norms for words expressing physical
and social pain. This may provide a useful tool for the selection of stimulus
materials in future studies on negative emotions and/or pain. We explored the
relationships between psycholinguistic, affective, and pain-related properties of
512 Italian words (nouns, adjectives, and verbs) conveying physical and social
pain by asking 1020 Italian participants to provide ratings of Familiarity, Age
of Acquisition, Imageability, Concreteness, Context Availability, Valence,
Arousal, Pain-Relatedness, Intensity, and Unpleasantness. We also collected data
concerning Length, Written Frequency (Subtlex-IT), N-Size, Orthographic
Levenshtein Distance 20, Neighbor Mean Frequency, and Neighbor Maximum Frequency
of each word. Interestingly, the words expressing social pain were rated as more
negative, arousing, pain-related, and conveying more intense and unpleasant
experiences than the words conveying physical pain.
PMID- 29958270
TI - Bone mineral density and bone remodeling markers in chronic low back pain
patients with active discopathy: A case-control exploratory study.
AB - OBJECTIVE: We aimed to compare bone mineral density (BMD) and bone remodeling
markers in chronic low back pain (cLBP) patients with and without active
discopathy (Modic 1 changes). DESIGN: We conducted a single center case-control
exploratory study. For 18 months, all patients referred to a tertiary care
physical medicine and rehabilitation department in France were consecutively
screened. Patients fulfilling the inclusion criteria were prospectively enrolled.
Cases were defined as cLBP patients with lumbar active discopathy detected on MRI
and controls as cLBP patients without active discopathy. Bone mineral density
(BMD) at the spine, femoral neck and total femur was assessed by dual-energy X
ray absorptiometry, and bone remodeling markers were assessed in fasting serum
samples. Overall, 37 cLBP patients (13 cases and 24 controls) fulfilled inclusion
criteria and were included. RESULTS: The median age was 42.0 years (Q1-Q3: 36.0
51.0) and mean (SD) LBP duration 72.3 (57.4) months. We found that BMD and levels
of bone remodeling markers in cLBP patients did not differ with and without
active discopathy. CONCLUSION: Our results do not support the association between
active discopathy and systemic bone fragility.
PMID- 29958271
TI - Physiological random processes in precision cancer therapy.
AB - Many different physiological processes affect the growth of malignant lesions and
their response to therapy. Each of these processes is spatially and genetically
heterogeneous; dynamically evolving in time; controlled by many other
physiological processes, and intrinsically random and unpredictable. The
objective of this paper is to show that all of these properties of cancer
physiology can be treated in a unified, mathematically rigorous way via the
theory of random processes. We treat each physiological process as a random
function of position and time within a tumor, defining the joint statistics of
such functions via the infinite-dimensional characteristic functional. The theory
is illustrated by analyzing several models of drug delivery and response of a
tumor to therapy. To apply the methodology to precision cancer therapy, we use
maximum-likelihood estimation with Emission Computed Tomography (ECT) data to
estimate unknown patient-specific physiological parameters, ultimately
demonstrating how to predict the probability of tumor control for an individual
patient undergoing a proposed therapeutic regimen.
PMID- 29958272
TI - Gaming behaviour with Pokemon GO and physical activity: A preliminary study with
medical students in Thailand.
AB - Pokemon GO becomes the most rapidly downloaded mobile application in history.
This study aimed to determine the physical activity of medical students, who
played Pokemon GO, and the change in their use of Pokemon GO and physical
activity over time. An observational study was conducted. Physical activity was
measured by using self-administered questionnaires at baseline (phase 0), 1 month
(phase 1) and 3 months (phase 2) post-Pokemon GO download. The changes in
physical activity (phase 0 to 1 and phase 1 to 2) were analysed using Wilcoxon
Signed Ranked test. The trend (3-point analysis) of physical activity from phase
0, 1 to 2 were analysed using Friedman's test. The relationship between physical
activity and time spent gaming was analysed by using Spearman's rank correlation.
Twenty-six participants (mean age 22.04+/-1.70 years) participated in the study.
There was no statistically significant change in physical activity during the
three-month period (p = 0.45). Only 11 participants (42.3%) were still playing
Pokemon GO 3 months after download. The key reasons for playing game were 'have
fun' and 'pass time/boredom'. The most common commuting mode to play the game was
walking; some drove a car or motorcycle while playing the game. There was no
correlation between physical activity and time spent gaming. This study
highlights how the lack of sustainability of the game and the motivation behind
using Pokemon GO as a game rather than a physical activity app may have
undermined the potential of using the game to improve physical activity. Further
studies need to explore the reasons for the lack of sustainability and how to
combine fun with behavioural change.
PMID- 29958274
TI - Understanding age variations in the migrant mortality advantage: An international
comparative perspective.
AB - This paper investigates age variations in foreign-born vs. native-born mortality
ratios in an international comparative perspective, with the purpose of gaining
insight into the mechanisms underlying the so-called migrant mortality advantage.
We examine the four main explanations that have been proposed in the literature
for the migrant mortality advantage (i.e., in-migration selection effects, out
migration selection effects, cultural effects, and data artifacts), and formulate
expectations as to whether they should generate an increase, a decrease, or no
change in relative mortality over the life course. Using data from France, the US
and the UK for periods around 2010, we then examine typical age patterns of
foreign-born vs. native-born mortality ratios in light of this theoretical
framework. We find that these mortality ratios vary greatly by age, with
important similarities across migrant groups and host countries. The most
systematic age pattern we find is a U-shape pattern: at the aggregate level,
migrants often experience excess mortality at young ages, then exhibit a large
advantage at adult ages (with the largest advantage around age 45), and finally
experience mortality convergence with natives at older ages. The explanation most
consistent with this pattern is the "in-migration selection effects" explanation.
By contrast, the "out-migration selection effects" explanation is poorly
supported by the observed patterns. Our age disaggregation also shows that
migrants at mid-adult ages experience mortality advantages that are often far
greater than typically documented in this literature. Overall, these results
reinforce the notion that migrants are a highly-selected population exhibiting
mortality patterns that poorly reflect their living conditions in host countries.
PMID- 29958273
TI - Leishmania major and Trypanosoma lewisi infection in invasive and native rodents
in Senegal.
AB - Bioinvasion is a major public health issue because it can lead to the
introduction of pathogens in new areas and favours the emergence of zoonotic
diseases. Rodents are prominent invasive species, and act as reservoirs in many
zoonotic infectious diseases. The aim of this study was to determine the link
between the distribution and spread of two parasite taxa (Leishmania spp. and
Trypanosoma lewisi) and the progressive invasion of Senegal by two commensal
rodent species (the house mouse Mus musculus domesticus and the black rat Rattus
rattus). M. m. domesticus and R. rattus have invaded the northern part and the
central/southern part of the country, respectively. Native and invasive rodents
were caught in villages and cities along the invasion gradients of both invaders,
from coastal localities towards the interior of the land. Molecular diagnosis of
the two trypanosomatid infections was performed using spleen specimens. In the
north, neither M. m. domesticus nor the native species were carriers of these
parasites. Conversely, in the south, 17.5% of R. rattus were infected by L. major
and 27.8% by T. lewisi, while very few commensal native rodents were carriers.
Prevalence pattern along invasion gradients, together with the knowledge on the
geographical distribution of the parasites, suggested that the presence of the
two parasites in R. rattus in Senegal is of different origins. Indeed, the
invader R. rattus could have been locally infected by the native parasite L.
major. Conversely, it could have introduced the exotic parasite T. lewisi in
Senegal, the latter appearing to be poorly transmitted to native rodents.
Altogether, these data show that R. rattus is a carrier of both parasites and
could be responsible for the emergence of new foci of cutaneous leishmaniasis, or
for the transmission of atypical human trypanosomiasis in Senegal.
PMID- 29958275
TI - Divide and conquer! Data-mining tools and sequential multivariate analysis to
search for diagnostic morphological characters within a plant polyploid complex
(Veronica subsect. Pentasepalae, Plantaginaceae).
AB - This study exhaustively explores leaf features seeking diagnostic characters to
aid the classification (assigning cases to groups, i.e. populations to taxa) in a
polyploid plant-species complex. A challenging case study was selected: Veronica
subsection Pentasepalae, a taxonomically intricate group. The "divide and
conquer" approach was implemented-that is, a difficult primary dataset was split
into more manageable subsets. Three techniques were explored: two data-mining
tools (artificial neural networks and decision trees) and one unsupervised
discriminant analysis. However, only the decision trees and discriminant analysis
were finally used to select diagnostic traits. A previously established
classification hypothesis based on other data sources was used as a starting
point. A guided discriminant analysis (i.e. involving manual character selection)
was used to produce a grouping scheme fitting this hypothesis so that it could be
taken as a reference. Sequential unsupervised multivariate analysis enabled the
recognition of all species and infraspecific taxa; however, a suboptimal
classification rate was achieved. Decision trees resulted in better
classification rates than unsupervised multivariate analysis, but three complete
taxa were misidentified (not present in terminal nodes). The variable selection
led to a different grouping scheme in the case of decision trees. The resulting
groups displayed low misclassification rates when analyzed using artificial
neural networks. The decision trees as well as the discriminant analysis are
recommended in the search of diagnostic characters. Due to the high sensitivity
that artificial neural networks have to the combination of input/output layers,
they are proposed as evaluation tools for morphometric studies. The "divide and
conquer" principle is a promising strategy, providing success in the present case
study.
PMID- 29958276
TI - Altered circadian genes expression in breast cancer tissue according to the
clinical characteristics.
AB - Breast cancer has a multifactorial etiology. One of the supposed and novel
mechanisms is an alteration of circadian gene expression. Circadian genes play a
crucial role in many physiological processes. These processes, such as genomic
stability, DNA repair mechanism and apoptosis, are frequently disrupted in breast
tumors. To assess the significance of circadian gene expression in breast cancer,
we carried out an analysis of CLOCK, BMAL1, NPAS2, PER1, PER2, PER3 and CRY1,
CRY2, TIMELESS, CSNK1E expression by the use of the quantitative Real-Time PCR
technique in tumor tissue and non-tumor adjacent normal tissue sampled from 107
women with a newly diagnosed disease. The obtained data were compared to the
clinical and histopathological features. PER1, PER2, PER3, CRY2 were found to be
significantly down-expressed, while CLOCK, TIMELESS were over-expressed in the
studied tumor samples compared to the non-tumor samples. Only gene expression of
CRY1 was significantly down-regulated with progression according to the TNM
classification. We found significantly decreased expression of CRY2, PER1, PER2
genes in the ER/PR negative breast tumors compared to the ER/PR positive tumors.
Additionally, expression of CRY2, NPAS2 genes had a decreased level in the poorly
differentiated tumors in comparison with the well and moderately differentiated
ones. Our results indicate that circadian gene expression is altered in breast
cancer tissue, which confirms previous observations from various animal and in
vitro studies.
PMID- 29958277
TI - A multiscale natural community and species-level vulnerability assessment of the
Gulf Coast, USA.
AB - Vulnerability assessments combine quantitative and qualitative evaluations of the
exposure, sensitivity, and adaptive capacity of species or natural communities to
current and future threats. When combined with the economic, ecological or
evolutionary value of the species, vulnerability assessments quantify the
relative risk to regional species and natural communities and can enable informed
prioritization of conservation efforts. Vulnerability assessments are common
practice in conservation biology, including the potential impacts of future
climate scenarios. However, geographic variation in scenarios and vulnerabilities
is rarely quantified. This gap is particularly limiting for informing ecosystem
management given that conservation practices typically vary by sociopolitical
boundaries rather than by ecological boundaries. To support prioritization of
conservation actions across a range of spatial scales, we conducted the Gulf
Coast Vulnerability Assessment (GCVA) for four natural communities and eleven
focal species around the Gulf of Mexico based on current and future threats from
climate change and land-use practices out to 2060. We used the Standardized Index
of Vulnerability and Value (SIVVA) tool to assess both natural community and
species vulnerabilities. We observed greater variation across ecologically
delineated subregions within the Gulf Coast of the U.S. than across climate
scenarios. This novel finding suggests that future vulnerability assessments
incorporate regional variation and that conservation prioritization may vary
across ecological subregions. Across subregions and climate scenarios the most
prominent threats were legacy effects, primarily from habitat loss and
degradation, that compromised the adaptive capacity of species and natural
communities. The second most important threats were future threats from sea-level
rise. Our results suggest that the substantial threats species and natural
communities face from climate change and sea-level rise would be within their
adaptive capacity were it not for historic habitat loss, fragmentation, and
degradation.
PMID- 29958278
TI - Size matters: An observational study investigating estimated height as a
reference size for calculating tidal volumes if low tidal volume ventilation is
required.
AB - PURPOSE: Acute lung injury is a life threatening condition often requiring
mechanical ventilation. Lung-protective ventilation with tidal volumes of 6 mL/kg
predicted body weight (PBW, calculated on the basis of a patient's sex and
height), is part of current recommended ventilation strategy. Hence, an exact
height is necessary to provide optimal mechanical ventilation. However, it is a
common practice to visually estimate the body height of mechanically ventilated
patients and use these estimates as a reference size for ventilator settings. We
aimed to determine if the common practice of estimating visual height to define
tidal volume reduces the possibility of receiving lung-protective ventilation.
METHODS: In this prospective observational study, 28 mechanically ventilated
patients had their heights visually estimated by 20 nurses and 20 physicians. All
medical professionals calculated the PBW and a corresponding tidal volume with 6
ml/kg/PBW on the basis of their visual estimation. The patients' true heights
were measured and the true PBW with a corresponding tidal volume was calculated.
Finally, estimates and measurements were compared. RESULTS: 1033 estimations were
undertaken by 153 medical professionals. The majority of the estimates were
imprecise and resulting data comprised taller body heights, higher PBW and higher
tidal volumes (all p<=0.01). When estimates of patients' heights are used as a
reference for tidal-volume definition, patients are exposed to mean tidal volumes
of 6.5 +/- 0.4 ml/kg/PBW. 526 estimation-based tidal volumes (51.1%) did not
provide lung-protective ventilation. Shorter subjects (<175cm) were a specific
risk group with an increased risk of not receiving lung protective ventilation
(OR 6.6; 95%CI 1.2-35.4; p = 0.02), while taller subjects had a smaller risk of
being exposed to inadequately high tidal volumes (OR 0.15; 95%CI 0.02-0.8; p =
0.02). Furthermore, we found an increased risk of overestimating if the assessor
was a female (OR 1.74; 95%CI 1.14-2.65; p = 0.01). CONCLUSION: The common
practice of visually estimating body height and using these estimates for
ventilator settings is imprecise and potentially harmful because it reduces the
chance of receiving lung-protective ventilation. Avoiding this practice increases
the patient safety. Instead, height should be measured as a standard procedure.
PMID- 29958279
TI - Ambient air pollution exposure and emergency department visits for substance
abuse.
AB - There is growing evidence supporting the notion that exposure to air pollution
can contribute to cognitive and psychiatric disorders, including depression and
suicide. Given the relationship between exposure to acute stressors and substance
abuse, the present study assessed the association between exposure to ambient air
pollution and emergency department (ED) visits for alcohol and drug abuse. ED
visit data selected according to International Classification of Disease (ICD-9)
coding 303 (alcohol dependence syndromes) and 305 (non-dependent abuse of drugs)
were collected in five hospitals in Edmonton, Canada. A time-stratified case
crossover design was used. Conditional logistic regression was applied to
calculate odds ratios (OR) and 95% confidence intervals (95% CI). Season,
temperature, and relative humidity were adjusted for using natural splines.
Results are reported for an increase in pollutant concentrations equivalent to
one interquartile range (IQR). Statistically significant positive associations
with substance abuse were observed for CO, NO2 and particulate matter with an
aerodynamic diameter less than 10 MUm (PM10) and 2.5 MUm (PM2.5). The strongest
results were obtained in the cold period (October-March) for 1-day lagged CO (OR
= 1.03, 95% CI: 1.01, 1.05, IQR = 0.4 ppm) and NO2 (OR = 1.04, 95% CI: 1.01,
1.07, IQR = 12.8 ppb); ORs were also significant for CO and NO2 with lags of 2 to
6 days and 2 to 7 days, respectively. The study suggests that, even at low
levels, increases in ambient CO, NO2, and PMs are associated with increased
hospital admissions for substance abuse, possibly as a result of impacts of air
quality on mental health or depression.
PMID- 29958280
TI - Computation predicts rapidly adapting mechanotransduction currents cannot account
for tactile encoding in Merkel cell-neurite complexes.
AB - Distinct firing properties among touch receptors are influenced by multiple,
interworking anatomical structures. Our understanding of the functions and
crosstalk of Merkel cells and their associated neurites-the end organs of slowly
adapting type I (SAI) afferents-remains incomplete. Piezo2 mechanically activated
channels are required both in Merkel cells and in sensory neurons for canonical
SAI responses in rodents; however, a central unanswered question is how rapidly
inactivating currents give rise to sustained action potential volleys in SAI
afferents. The computational model herein synthesizes mechanotransduction
currents originating from Merkel cells and neurites, in context of skin mechanics
and neural dynamics. Its goal is to mimic distinct spike firing patterns from
wildtype animals, as well as Atoh1 knockout animals that completely lack Merkel
cells. The developed generator function includes a Merkel cell mechanism that
represents its mechanotransduction currents and downstream voltage-activated
conductances (slower decay of current) and a neurite mechanism that represents
its mechanotransduction currents (faster decay of current). To mimic sustained
firing in wildtype animals, a longer time constant was needed than the 200 ms
observed for mechanically activated membrane depolarizations in rodent Merkel
cells. One mechanism that suffices is to introduce an ultra-slowly inactivating
current, with a time constant on the order of 1.7 s. This mechanism may drive the
slow adaptation of the sustained response, for which the skin's viscoelastic
relaxation cannot account. Positioned within the sensory neuron, this source of
current reconciles the physiology and anatomical characteristics of Atoh1
knockout animals.
PMID- 29958281
TI - Duplication of a Pks gene cluster and subsequent functional diversification
facilitate environmental adaptation in Metarhizium species.
AB - The ecological importance of the duplication and diversification of gene clusters
that synthesize secondary metabolites in fungi remains poorly understood. Here,
we demonstrated that the duplication and subsequent diversification of a gene
cluster produced two polyketide synthase gene clusters in the cosmopolitan fungal
genus Metarhizium. Diversification occurred in the promoter regions and the exon
intron structures of the two Pks paralogs (Pks1 and Pks2). These two Pks genes
have distinct expression patterns, with Pks1 highly expressed during conidiation
and Pks2 highly expressed during infection. Different upstream signaling pathways
were found to regulate the two Pks genes. Pks1 is positively regulated by Hog1
MAPK, Slt2-MAPK and Mr-OPY2, while Pks2 is positively regulated by Fus3-MAPK and
negatively regulated by Mr-OPY2. Pks1 and Pks2 have been subjected to positive
selection and synthesize different secondary metabolites. PKS1 is involved in
synthesis of an anthraquinone derivative, and contributes to conidial
pigmentation, which plays an important role in fungal tolerance to UV radiation
and extreme temperatures. Disruption of the Pks2 gene delayed formation of
infectious structures and increased the time taken to kill insects, indicating
that Pks2 contributes to pathogenesis. Thus, the duplication of a Pks gene
cluster and its subsequent functional diversification has increased the adaptive
flexibility of Metarhizium species.
PMID- 29958282
TI - Data fusion of body-worn accelerometers and heart rate to predict VO2max during
submaximal running.
AB - Maximal oxygen uptake (VO2max) is often used to assess an individual's
cardiorespiratory fitness. However, measuring this variable requires an athlete
to perform a maximal exercise test which may be impractical, since this test
requires trained staff and specialized equipment, and may be hard to incorporate
regularly into training programs. The aim of this study is to develop a new model
for predicting VO2max by exploiting its relationship to heart rate and
accelerometer features extracted during submaximal running. To do so, we analyzed
data collected from 31 recreational runners (15 men and 16 women) aged 19-26
years who performed a maximal incremental test on a treadmill. During this test,
the subjects' heart rate and acceleration at three locations (the upper back, the
lower back and the tibia) were continuously measured. We extracted a wide variety
of features from the measurements of the warm-up and the first three stages of
the test and employed a data-driven approach to select the most relevant ones.
Furthermore, we evaluated the utility of combining different types of features.
Empirically, we found that combining heart rate and accelerometer features
resulted in the best model with a mean absolute error of 2.33 ml ? kg-1 ? min-1
and a mean absolute percentage error of 4.92%. The model includes four features:
gender, body mass, the inverse of the average heart rate and the inverse of the
variance of the total tibia acceleration during the warm-up stage of the
treadmill test. Our model provides a practical tool for recreational runners in
the same age range to estimate their VO2max from submaximal running on a
treadmill. It requires two body-worn sensors: a heart rate monitor and an
accelerometer positioned on the tibia.
PMID- 29958283
TI - Molecular detection of Leishmania infantum DNA and host blood meal identification
in Phlebotomus in a hypoendemic focus of human leishmaniasis in northern Algeria.
AB - BACKGROUND: Leishmania parasites are transmitted by female phlebotomine sand
flies that maintain the enzootic cycle by circulating between sylvatic and
domestic mammals. Humans are part of this cycle as accidental hosts due to the
vector's search for a source of blood. In Algeria, Human Leishmaniases (HL) are
endemic and represent a serious public health problem because of their high
annual incidence and their spread across the country. The aim of this study is to
identify sand fly species fauna (vectors of Leishmania), determine their
infection rate and identify their feeding preferences using molecular tools in a
hypoendemic focus of HL located in the province of Tipaza, northern Algeria.
METHODOLOGY/PRINCIPAL FINDINGS: An entomological survey using CDC light traps was
conducted between July and October of 2015 in four HL affected peri-urban
locations in the province of Tipaza, northern Algeria. Sand flies were identified
using the morphological criteria of the genitalia for the males and spermathecae
for the females. Leishmania DNA was detected in pooled female sand flies (N = 81
pools with 8-10 specimens per pool) using quantitative real-time polymerase chain
reaction (qPCR) targeting two different genes: kDNA-PCR and 18S rRNA. To identify
their blood meal sources, blood-fed female sand flies were analyzed by PCR
sequencing targeting the vertebrate cytochrome c oxidase I (COI) gene. A total of
4,045 sand flies were caught, of which 3,727 specimens were morphologically
identified. Seven species were recorded: P. (L.) perniciosus (50.28%), P. (L.)
perfiliewi (26.13%), P. (L.) longicuspis (21.92%), Sergentomyia (S.) minuta
(0.85%), P. (P.) papatasi (0.42%), P. (L.) langeroni (0.32%) and P. (L.) ariasi
(0.05%). Afterwards, 740 female specimens were randomly selected and divided into
81 pools and were then screened to investigate the presence of Leishmania spp. L.
infantum DNA was detected in three pools, corresponding to three sand fly
specimens (one each). The infection rate was 0.33% (2/600) for P. (L.)
perniciosus and 2.56% (1/39) for P. (L.) perfiliewi. Analysis of the blood
feeding sources (N = 88 specimens) revealed that sand flies belonging to
Larroussius subgenera, mainly (71.5%) feed on small ruminants. Human blood is the
second feeding source (17%), eight specimens (9%) were found to feed on equines
and no domestic reservoir (dog) blood was found. CONCLUSIONS/SIGNIFICANCE: The
presence of human leishmaniasis cases, the high abundance of Phlebotomus
(Larroussius) species which are proven or suspected vectors of L. infantum, and
the detection of L. infantum DNA from its natural vectors (P. (L.) perniciosus,
P. (L.) perfiliewi), in addition to the blood-feeding of positive females for L.
infantum on humans blood, prove that the major elements of the epidemiological
transmission cycle of L. infantum are present and indicate risk factors for an
outbreak of the disease in the province of Tipaza.
PMID- 29958284
TI - Therapeutic body wraps (TBW) for treatment of severe injurious behaviour in
children with autism spectrum disorder (ASD): A 3-month randomized controlled
feasibility study.
AB - INTRODUCTION: The use of therapeutic body wraps (TBW) has been reported in small
series or case reports, but has become controversial. OBJECTIVES: This is a
feasibility, multicentre, randomized, controlled, open-label trial with blinded
outcome assessment (PROBE design). SETTING: Children with autism and severe
injurious behaviours (SIB) were enrolled from 13 specialized clinics.
INTERVENTIONS: Dry-sheet TBW (DRY group) vs. wet-sheet TBW (WET group). PRIMARY
OUTCOME MEASURES: 3-month change in the Aberrant Behaviour Checklist irritability
score (ABC-irritability) within per-protocol (PP) sample. RESULTS: From January
2008 to January 2015, we recruited 48 children (age range: 5.9 to 9.9 years,
78.1% male). Seven patients (4 in the DRY group, 3 in the WET group) were dropped
from the study early and were excluded from PP analysis. At endpoint, ABC
irritability significantly improved in both groups (means (standard deviation) =
11.15 (8.05) in the DRY group and -10.57 (9.29) in the WET group), as did the
other ABC scores and the Children Autism Rating scale score. However, there was
no significant difference between groups. All but 5 patients were rated as much
or very much improved. A repeated-measures analysis confirmed the significant
improvement in ABC-irritability scores according to time (p < .0001), with no
significant difference between the two groups (group effect: p = .55; interaction
time x group: p = .27). Pooling both groups together, the mean 3-month change
from baseline in ABC-irritability score was -10.90 (effect size = 1.59, p <
.0001). CONCLUSIONS: We found that feasibility was overall satisfactory with a
slow recruitment rate and a rather good attrition rate. TBW was a safe
complementary therapy in this population. There was no difference between wet and
dry TBW at 3 months, and ABC-irritability significantly decreased with both wet
and dry sheet TBW. To assess whether TBW may constitute an alternative to
medication or behavioural intervention for treating SIB in ASD patients, a larger
randomized comparative trial (e.g. TBW vs. antipsychotics) is warranted. TRIAL
REGISTRATION: ClinicalTrials.gov NCT03164746.
PMID- 29958285
TI - Molecular identification and functional characterization of the cathepsin B gene
(Ab-cb-1) in the plant parasitic nematode Aphelenchoides besseyi.
AB - The rice white tip nematode, Aphelenchoides besseyi, is widely distributed in
rice planting areas worldwide and causes serious economic losses. Cathepsin genes
have been demonstrated to have importance in studying the reproduction,
development, pathogenicity, and control methods of plant nematodes. In this
paper, a novel cathepsin B gene, Ab-cb-1, was found and cloned. The Ab-cb-1 gene
was 1347 bp in length and encodes 369 amino acids. The Ab-CB-1 protein contains
characteristic occluding loops but no signal peptide. A homology analysis showed
that Ab-CB-1 had the highest identity value (64%) to the known amino acid
sequence of cathepsin B-like cysteine protease 6 from Toxocara canis. When Ab-cb
1 was expressed in a prokaryotic system, the protein massed approximately 45 kDa
and could decompose carrot callus. Ab-cb-1 mRNA was localized in the nematode
intestine. The relative expression level of Ab-cb-1 in the A. besseyi Ab-S24
population, which had high reproductivity, was approximately 6.9 times that in
the Ab-N10 population, which had low reproductivity, and the difference was
significant (p<0.05). The Ab-cb-1 expression level was highest in females; the
expression levels in males, juveniles and eggs were 30%, 12.2% and 5% of that in
females, respectively, and the differences were significant among all four stages
(p<0.05). Nematodes of the Ab-S24 population were treated with Ab-cb-1 dsRNA for
12 h, 24 h, 36 h and 48 h, and their reproduction decreased with increasing time.
These results demonstrated that Ab-CB-1 was a digestive enzyme with hydrolytic
protease properties and that Ab-cb-1 played an important role in the reproduction
of A. besseyi.
PMID- 29958286
TI - Sensory information and the perception of verticality in post-stroke patients.
Another point of view in sensory reweighting strategies.
AB - INTRODUCTION: Perception of verticality is highly related to balance control in
human. Head-on-body tilt <60 degrees results in the E-effect, meaning that a
tilt of the perceived vertical is observed contralateral to the head tilt in the
frontal plane. Furthermore, somatosensory loss also impacts the accuracy of
verticality perception. However, when several input sources are absent or biased,
less options for sensory weighting and balance control occur. Therefore, this
study aims to identify the E-effect and assess the effect of somatosensory loss
on the extent of the E-effect. METHODS: All patients with a first stroke admitted
to a Belgian rehabilitation hospital were eligible for inclusion. Patients aged
above 80 with other neurological and orthopaedic impairments as well as
brainstem, cerebellar or multiple lesions were excluded. In addition, patients
with visuospatial neglect and pusher behaviour were also excluded as this can
affect verticality perception. The Rivermead Assessment of Somatosensory
Performance (RASP), the Subjective Visual (SVV) and Subjective Postural (SPV)
Vertical Test were administered. RESULTS: In total, 37 patients were included in
the analysis of which 24 patients completed both SVV and SPV assessment. Results
show that the E-effect occurred in our sample of stroke survivors for both SVV
and SPV. In addition, the presence of somatosensory loss will increase the E
effect in both SVV as SPV assessment. A significant difference in verticality
perception was noted for both SVV and SPV between the group with no (SVV: 5.13
degrees (6.92); SPV: 0.30 degrees (1.85)) and highly severe (SVV: 10.54 degrees
(13.19); SPV: 5.96 degrees (9.27)) sensory loss. CONCLUSIONS: The E-effect occurs
in stroke subjects and increases when patients experience somatosensory loss.
This suggests that the lack of available afferent information impede estimation
of verticality. Therefore, stroke survivors have fewer alternative input sources
as a result of impairments, leading to fewer options about sensory reweighting
strategies and balance recovery after perturbations.
PMID- 29958287
TI - Similarities in the evolution of plants and cars.
AB - While one system is animate and the other inanimate, both plants and cars are
powered by a highly successful process which has evolved in a changing
environment. Each process (the photosynthetic pathway and the car engine,
respectively) originated from a basic scheme and evolved greater efficiency by
adding components to the existing structure, which has remained largely
unchanged. Here we present a comparative analysis of two variants on the original
C3 photosynthetic pathway (C4 and CAM) and two variants on the internal
combustion engine (the turbocharger and the hybrid electric vehicle). We compare
the timeline of evolution, the interaction between system components, and the
effects of environmental conditions on both systems. This analysis reveals
striking similarities in the development of these processes, providing insight as
to how complex systems-both natural and built-evolve and adapt to changing
environmental conditions in a modular fashion.
PMID- 29958288
TI - The importance of using public data to validate reported associations.
PMID- 29958289
TI - Groove in drum patterns as a function of both rhythmic properties and listeners'
attitudes.
AB - Music psychology defines groove as humans' pleasureable urge to move their body
in synchrony with music. Past research has found that rhythmic syncopation, event
density, beat salience, and rhythmic variability are positively associated with
groove. This exploratory study investigates the groove effect of 248
reconstructed drum patterns from different popular music styles (pop, rock, funk,
heavy metal, rock'n'roll, hip hop, soul, R&B). It aims at identifying factors
that might be relevant for groove and worth investigating in a controlled setting
in the future. Drum patterns of eight bars duration, chosen from 248 popular
music tracks, have been transcribed and audio reconstructions have been created
on the basis of sound samples. During an online listening experiment, 665
participants rated the reconstructions a total of 8,329 times using a groove
questionnaire. Results show that, among 15 tested variables, syncopation (R2 =
0.010) and event density (R2 = 0.011) were positively associated with the groove
ratings. These effects were stronger in participants who were music
professionals, compared to amateur musicians or mere listeners. A categorisation
of the stimuli according to structural aspects was also associated with groove
(R2 = 0.018). Beat salience, residual microtiming and rhythmic variability showed
no effect on the groove ratings. Participants' familiarity with a drum pattern
had a positive influence on the groove ratings (eta2 = 0.051). The largest
isolated effect was measured for participants' style bias (R2 = 0.123): groove
ratings tended to be high if participants had the impression that the drum
pattern belonged to a style they liked. Combined, the effects of style bias and
familiarity (R2 = 0.152) exceeded the other effects as predictors for groove by a
wide margin. We conclude that listeners' taste, musical biographies and expertise
have a strong effect on their groove experience. This motivates groove research
not to focus on the music alone, but to take the listeners into account as well.
PMID- 29958290
TI - Value of sample information in dynamic, structurally uncertain resource systems.
AB - Few if any natural resource systems are completely understood and fully observed.
Instead, there almost always is uncertainty about the way a system works and its
status at any given time, which can limit effective management. A natural
approach to uncertainty is to allocate time and effort to the collection of
additional data, on the reasonable assumption that more information will
facilitate better understanding and lead to better management. But the collection
of more data, either through observation or investigation, requires time and
effort that often can be put to other conservation activities. An important
question is whether the use of limited resources to improve understanding is
justified by the resulting potential for improved management. In this paper we
address directly a change in value from new information collected through
investigation. We frame the value of information in terms of learning through the
management process itself, as well as learning through investigations that are
external to the management process but add to our base of understanding. We
provide a conceptual framework and metrics for this issue, and illustrate them
with examples involving Florida scrub-jays (Aphelocoma coerulescens).
PMID- 29958291
TI - Enhancing radiosensitivity of melanoma cells through very high dose rate pulses
released by a plasma focus device.
AB - Radiation therapy is a useful and standard tumor treatment strategy. Despite
recent advances in delivery of ionizing radiation, survival rates for some cancer
patients are still low because of recurrence and radioresistance. This is why
many novel approaches have been explored to improve radiotherapy outcome. Some
strategies are focused on enhancement of accuracy in ionizing radiation delivery
and on the generation of greater radiation beams, for example with a higher dose
rate. In the present study we proposed an in vitro research of the biological
effects of very high dose rate beam on SK-Mel28 and A375, two radioresistant
human melanoma cell lines. The beam was delivered by a pulsed plasma device, a
"Mather type" Plasma Focus for medical applications. We hypothesized that this
pulsed X-rays generator is significantly more effective to impair melanoma cells
survival compared to conventional X-ray tube. Very high dose rate treatments were
able to reduce clonogenic efficiency of SK-Mel28 and A375 more than the X-ray
tube and to induce a greater, less easy-to-repair DNA double-strand breaks. Very
little is known about biological consequences of such dose rate. Our
characterization is preliminary but is the first step toward future clinical
considerations.
PMID- 29958292
TI - A classification modeling approach for determining metabolite signatures in
osteoarthritis.
AB - Multiple factors can help predict knee osteoarthritis (OA) patients from healthy
individuals, including age, sex, and BMI, and possibly metabolite levels. Using
plasma from individuals with primary OA undergoing total knee replacement and
healthy volunteers, we measured lysophosphatidylcholine (lysoPC) and
phosphatidylcholine (PC) analogues by metabolomics. Populations were stratified
on demographic factors and lysoPC and PC analogue signatures were determined by
univariate receiver-operator curve (AUC) analysis. Using signatures, multivariate
classification modeling was performed using various algorithms to select the most
consistent method as measured by AUC differences between resampled training and
test sets. Lists of metabolites indicative of OA [AUC > 0.5] were identified for
each stratum. The signature from males age > 50 years old encompassed the
majority of identified metabolites, suggesting lysoPCs and PCs are dominant
indicators of OA in older males. Principal component regression with logistic
regression was the most consistent multivariate classification algorithm tested.
Using this algorithm, classification of older males had fair power to classify OA
patients from healthy individuals. Thus, individual levels of lysoPC and PC
analogues may be indicative of individuals with OA in older populations,
particularly males. Our metabolite signature modeling method is likely to
increase classification power in validation cohorts.
PMID- 29958293
TI - Sociodemographic determinants and health outcome variation in individuals with
type 1 diabetes mellitus: A register-based study.
AB - BACKGROUND: Socioeconomic status, origin or demographic attributes shall not
determine the quality of healthcare delivery, according to e.g. United Nations
and European Union rules. Health equity has been defined as the absence of
systematic disparities and unwarranted differences between groups defined by
differences in social advantages. A study was performed to investigate whether
this was applicable to type 1 diabetes mellitus (T1D) care in a setting with
universal, tax-funded healthcare. METHODS: This retrospective registry-study was
based on patient-level data from individuals diagnosed with T1D during 2010-2011
(n = 16,367) in any of seven Swedish county councils (covering ~65% of the
Swedish population). Health equity in T1D care was analysed through multivariate
regression analyses on absolute HbA1c level at one-year follow-up, one-year
change in estimated glomerular filtration rate (eGFR) and one-year change in
cardiovascular risk score, using selected sociodemographic dimensions as case-mix
factors. RESULTS: Higher educational level was consistently associated with lower
levels of HbA1c, and so was being married. Never married was associated with
worse eGFR development, and lower educational level was associated with higher
cardiovascular risk. Women had higher HbA1c levels than men, and glucose control
was significantly worse in patients below the age of 25. CONCLUSION: Patients'
sociodemographic profile was strongly associated with absolute levels of risk
factor control in T1D, but also with an increased annual deterioration in eGFR.
Whether these systematic differences stem from patient-related problems or
healthcare organisational shortcomings is a matter for further research. The
results, though, highlight the need for intensified diabetes management education
and secondary prevention directed towards T1D patients, taking sociodemographic
characteristics into account.
PMID- 29958294
TI - The analysis of genome composition and codon bias reveals distinctive patterns
between avian and mammalian circoviruses which suggest a potential recombinant
origin for Porcine circovirus 3.
AB - Members of the genus Circovirus are host-specific viruses, which are totally
dependent on cell machinery for their replication. Consequently, certain mimicry
of the host genome features is expected to maximize cellular replicative system
exploitation and minimize the recognition by the innate immune system. In the
present study, the analysis of several genome composition and codon bias
parameters of circoviruses infecting avian and mammalian species demonstrated the
presence of quite distinctive patterns between the two groups. Remarkably, a
higher deviation from the expected values based only on mutational patterns was
observed for mammalian circoviruses both at dinucleotide and codon levels.
Accordingly, a stronger selective pressure was estimated to shape the genome of
mammalian circoviruses, particularly in the Cap encoding gene, compared to avian
circoviruses. These differences could be attributed to different physiological
and immunological features of the two host classes and suggest a trade-off
between a tendency to optimize the capsid protein translation while minimizing
the recognition of the genome and the transcript molecules. Interestingly, the
recently identified Porcine circovirus 3 (PCV-3) had an intermediate pattern in
terms of genome composition and codon bias. Particularly, its Rep gene appeared
closely related to other mammalian circoviruses (especially bat circoviruses)
while the Cap gene more closely resembled avian circoviruses. These evidences,
coupled with the high selective forces apparently modelling the PCV-3 Cap gene
composition, suggest the potential recombinant origin, followed or preceded by a
host jump, of this virus.
PMID- 29958295
TI - The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like
receptor activation.
AB - The activity of Cullin-RING ubiquitin E3 ligases (CRL) is regulated by NEDD8
modification. DCN-like proteins promote Cullin neddylation as scaffold-like E3s.
One DCNL, DCNL5, is highly expressed in immune tissue. Here, we provide evidence
that DCNL5 may be involved in innate immunity, as it is a direct substrate of the
kinase IKKalpha during immune signalling. We find that upon activation of Toll
like receptors, DCNL5 gets rapidly and transiently phosphorylated on a specific N
terminal serine residue (S41). This phosphorylation event is specifically
mediated by IKKalpha and not IKKbeta. Our data for the first time provides
evidence that DCNL proteins are post-translationally modified in an inducible
manner. Our findings also provide the first example of a DCNL member as a kinase
substrate in a signalling pathway, indicating that the activity of at least some
DCNLs may be regulated.
PMID- 29958296
TI - Origins and wanderings of the Finnish hunting spitzes.
AB - Deducing the evolutionary histories of dog breeds can be challenging due to
convergent traits and frequent admixture. In this report, we have explored the
relationships of indigenous Finnish hunting spitz breeds among other northern
Eurasian hunting breeds using commercially available SNP analysis (the MyDogDNA
panel test). We find that Nordic hunting breeds Finnish Spitz, Nordic Spitz and
the Karelian Bear Dog, as well as the reindeer herding Lapphund and Lapponian
herder are all closely related and have common origins with the northeastern
Eurasian Laika breeds, rather than with other Scandinavian Spitz breeds, such as
Elkhounds and Swedish Vallhund. By tracing admixture events and direction of gene
flow, we also elucidate the complex interactions between the breeds and provide
new insight into the history of Swedish Elkhound and Russian-European Laika. The
findings, together with an analysis of genetic differentiation between the
populations, not only help to understand the origins of the breeds but also
provide interesting possibilities to revive genetic diversity, lost during the
breeding history, by backcrossing breeds to their hypothetical ancestry.
PMID- 29958297
TI - Correction: Myasthenia gravis seronegative for acetylcholine receptor antibodies
in South Korea: Autoantibody profiles and clinical features.
AB - [This corrects the article DOI: 10.1371/journal.pone.0193723.].
PMID- 29958298
TI - Sweet taste receptor inhibitors: Potential treatment for equine insulin
dysregulation.
AB - Hyperinsulinemia is a major risk factor for equine laminitis, a debilitating and
painful foot condition. Sweet taste receptor (T1R2/3) inhibitors have been used
to reduce the insulin and glucose responses to oral carbohydrates in other
species. However, their effect in horses has not been investigated. It would be
useful to be able to attenuate the large post-prandial insulin response that
typically occurs when a carbohydrate-rich meal is fed to insulin-dysregulated
horses. Here we have determined the efficacy of two T1R2/3 inhibitors, lactisole
and Gymnema sylvestre, for reducing glucose uptake by the equine small intestine
in vitro; and post-prandial insulin secretion in ponies in vivo, following a
carbohydrate-based meal. We used gas chromatography-mass spectrometry to measure
2-deoxyglucose uptake by explants of small intestine, in the presence and absence
of the T1R2/3 inhibitors. Lactisole and G sylvestre reduced 2-deoxyglucose uptake
by the intestinal explants by 63% (P = 0.032) and 73% (P = 0.047), respectively,
compared to control samples. The study in vivo investigated the effect of the
inhibitors on the blood glucose and serum insulin responses to a meal containing
D-glucose. Three doses of each inhibitor were tested using a Latin square design,
and each dose was compared to a meal with no inhibitor added. Lactisole had no
effect on glucose and insulin concentrations, whereas G sylvestre was partially
effective at reducing post-prandial blood glucose (by ~10%) and serum insulin
concentrations (~25%) in seven ponies, with a most effective dose of 10 mg/kg
bodyweight. These data provide preliminary support that T1R2/3 inhibitors may be
a useful therapeutic strategy for the management of equine insulin dysregulation
and the prevention of laminitis. However, further optimisation of the dose and
delivery method for these compounds is required, as well as a direct
investigation of their activity on the equine sweet taste receptor.
PMID- 29958299
TI - TV listening and hearing aids.
AB - TV listening plays a large role in the lives of hearing-impaired (HI)
individuals. Yet, few studies have examined TV listening in this group. In this
paper, we report the findings of an online survey on TV listening conducted among
HI individuals with and without hearing aids (HAs) in the United States in 2015.
The research investigated if and in what form TV listening experiences of unaided
and aided HI individuals might differ with regard to their viewing habits,
difficulties they experience, and compensation strategies they employ. 515 HI
people of ages 50+ years participated, 260 of whom owned HAs. HA users reported
that they watched TV or video on average for 6 hours 10 min per day, 57 minutes
longer than the duration reported by non-HA owners. Furthermore, HA users
indicated fewer difficulties when watching TV than non-HA owners, suggesting that
HA usage alleviated difficulties with TV listening. Nevertheless, the most
frequent problems were still encountered by more than 39% of the HA users.
Difficulties increased with greater self-reported unaided hearing disability, and
female participants indicated more problems than male participants. Finally,
those with carpeted floors reported fewer difficulties than those without
carpets. The most frequently used compensation strategies were changing TV or HA
volumes and using closed captioning. Only few HA users used audio streaming
accessories. Given the exploratory nature of this study, further research is
needed to inform interventions and improve the TV listening experiences of HI
viewers.
PMID- 29958300
TI - Development and testing of AAV-delivered single-chain variable fragments for the
treatment of methamphetamine abuse.
AB - Methamphetamine (METH) substance abuse disorders have major impact on society,
yet no medications have proven successful at preventing METH relapse or cravings.
Anti-METH monoclonal antibodies can reduce METH brain concentrations; however,
this therapy has limitations, including the need for repeated dosing throughout
the course of addiction recovery. An adeno-associated viral (AAV)-delivered DNA
sequence for a single-chain variable fragment could offer long-term, continuous
expression of anti-METH antibody fragments. For these studies, we injected mice
via tail vein with 1 x 1012 vector genomes of two AAV8 scFv constructs and
measured long-term expression of the antibody fragments. Mice expressed each scFv
for at least 212 days, achieving micromolar scFv concentrations in serum. In
separate experiments 21 days and 50 days after injecting mice with AAV-scFvs mice
were challenged with METH in vivo. The circulating scFvs were capable of
decreasing brain METH concentrations by up to 60% and sequestering METH in serum
for 2 to 3 hrs. These results suggest that AAV-delivered scFv could be a
promising therapy to treat methamphetamine abuse.
PMID- 29958301
TI - Introducing chaos behavior to kernel relevance vector machine (RVM) for four
class EEG classification.
AB - This paper addresses a chaos kernel function for the relevance vector machine
(RVM) in EEG signal classification, which is an important component of Brain
Computer Interface (BCI). The novel kernel function has evolved from a chaotic
system, which is inspired by the fact that human brain signals depict some
chaotic characteristics and behaviors. By introducing the chaotic dynamics to the
kernel function, the RVM will be enabled for higher classification capacity. The
proposed method is validated within the framework of one versus one common
spatial pattern (OVO-CSP) classifier to classify motor imagination (MI) of four
movements in a public accessible dataset. To illustrate the performance of the
proposed kernel function, Gaussian and Polynomial kernel functions are considered
for comparison. Experimental results show that the proposed kernel function
achieved higher accuracy than Gaussian and Polynomial kernel functions, which
shows that the chaotic behavior consideration is helpful in the EEG signal
classification.
PMID- 29958303
TI - The intricate relationship between gut and kidney.
PMID- 29958302
TI - Innate immune sensor LGP2 is cleaved by the Leader protease of foot-and-mouth
disease virus.
AB - The RNA helicase LGP2 (Laboratory of Genetics and Physiology 2) is a non
signaling member of the retinoic acid-inducible gene-I (RIG-I)-like receptors
(RLRs), whose pivotal role on innate immune responses against RNA viruses is
being increasingly uncovered. LGP2 is known to work in synergy with melanoma
differentiation-associated gene 5 (MDA5) to promote the antiviral response
induced by picornavirus infection. Here, we describe the activity of the foot-and
mouth disease virus (FMDV) Leader protease (Lpro) targeting LGP2 for cleavage.
When LGP2 and Lpro were co-expressed, cleavage products were observed in an Lpro
dose-dependent manner while co-expression with a catalytically inactive Lpro
mutant had no effect on LGP2 levels or pattern. We further show that Lpro
localizes and immunoprecipitates with LGP2 in transfected cells supporting their
interaction within the cytoplasm. Evidence of LGP2 proteolysis was also detected
during FMDV infection. Moreover, the inhibitory effect of LGP2 overexpression on
FMDV growth observed was reverted when Lpro was co-expressed, concomitant with
lower levels of IFN-beta mRNA and antiviral activity in those cells. The Lpro
target site in LGP2 was identified as an RGRAR sequence in a conserved helicase
motif whose replacement to EGEAE abrogated LGP2 cleavage by Lpro. Taken together,
these data suggest that LGP2 cleavage by the Leader protease of aphthoviruses may
represent a novel antagonistic mechanism for immune evasion.
PMID- 29958304
TI - Probiotics in the treatment of chronic kidney disease: a systematic review.
AB - Chronic kidney disease (CKD) is a syndrome caused by the progressive reduction of
renal function. This study aimed to systematically examine the effects of
supplementation with probiotics in the treatment of CKD. Searches were carried
out on databases MEDLINE (PubMed), SciELO, Cochrane, and Clinical Trials. Two
independent reviewers selected the studies from which data was extracted. The
search included papers written in English and Portuguese published in the 2012
2016 period describing randomized clinical trials. Eight of the 82 eligible
articles met the inclusion criteria. Sample size ranged from 18 to 101
individuals with CKD. The duration of the included studies varied from four to 24
weeks. Most of the included articles reported positive effects in renal function
and decreased levels of urea, blood urea nitrogen, ammonia, plasma p-cresol, p
cresyl sulfate, and indoxyl sulfate.
PMID- 29958306
TI - Managing Transitions.
PMID- 29958305
TI - The impact of surgical intervention on renal function in cystinuria.
AB - INTRODUCTION: Cystinuria is an autosomal recessive disorder due to intestinal and
renal transport defects in cystine and dibasic amino acids, which result in
recurrent urolithiasis and surgical interventions. This study aimed to assess the
impact of surgical interventions on renal function by analyzing estimated
glomerular filtration rates. METHODS: Thirteen pediatric patients with
cystinuria, who were followed-up in a single tertiary institution between 2004
and 2016, were included in the study. Medical records were reviewed to collect
data on clinical presentation of patients, urine parameters, stone formation,
medical treatment, surgical intervention, stone recurrence after surgical
procedure, stone analysis, ultrasonography, 99m-technetium dimercaptosuccinic
acid (99mTc-DMSA) radionuclide imaging results, and follow-up time. Creatinine
clearances estimated by modified Schwartz (eGFR) formula before and after surgery
were used to assess renal function and compared statistically. RESULTS: Nine
patients (69.2%) had renal scarring which were detected with 99mTc-DMSA
radionuclide imaging. In ten patients (76.9%), open surgical intervention for
stones were needed during follow-up. Significant difference was not detected
between eGFR before and after surgical intervention (mean 92 versus 106, p =
0.36). Nine of the patients (69.2%) were stone free in the last ultrasonographic
examination. Relapses of stone after surgery were seen in 66.6% of patients who
underwent surgical intervention. CONCLUSIONS: Surgical interventions for urinary
stones are commonly required in patients with cystinuria. Renal scarring is a
prevalent finding in cystinuric patients. Surgical interventions have no negative
impact on eGFR in patients with cystinuria according to the present study.
PMID- 29958307
TI - Erratum for "Influence of Short-Term Study Abroad Experiences on Community Health
Baccalaureate Students".
PMID- 29958308
TI - Kirkpatrick's Evaluation of Simulation and Debriefing in Health Care Education: A
Systematic Review.
AB - BACKGROUND: Simulation is an integral component of health care education.
Research suggests a positive relationship between simulation and learning
outcomes. Kirkpatrick's framework is a four-level model based on the premise that
learning resulting from training programs can be classified into four levels:
reaction, learning, behavior, and results. Evaluation of educational impact
provides valuable feedback to educators that may assist with development and
improvement of teaching methods. METHOD: This review is based on the PRISMA
guidelines for conducting a systematic review. Inclusion criteria included
articles (a) written in the English language, (b) published between 2000 and
2016, (c) describing a debriefing intervention after high-fidelity patient
simulation, and (d) based in health care. RESULTS: Thirteen studies met criteria
for inclusion in the review. CONCLUSION: Results indicated a paucity of studies
at the highest levels of evaluation, indicating an area where future research is
needed to assist with the development and improvement of simulation education. [J
Nurs Educ. 2018;57(7):393-398.].
PMID- 29958309
TI - Constructing Writing Practices in Nursing.
AB - BACKGROUND: Although the quality of student writing is often lamented by faculty,
writing instruction is an area of nursing education that has received little
attention. Nursing programs rarely teach writing from a disciplinary perspective,
and promoting the drilling of basic skills, such as grammar, has failed to engage
student writers. METHOD: A critical examination of the history of writing
research, the nursing academic context, and the epistemology of writing as
meaning making will provide the rationale behind a need for a new perspective on
nurses' writing. RESULTS: A model to support socially constructed writing is
proposed, which explores the writer's identity, relational aspects of writing,
creative and emotional knowing, and the writing context. CONCLUSION: This article
continues the conversation about re-visioning and enhancing the value of writing
within the nursing profession. The knowledge created while writing can contribute
to stimulating thinking, decision making in practice, and identity formation of
nurses. [J Nurs Educ. 2018;57(7):399-407.].
PMID- 29958310
TI - A Rubric to Assess Students' Clinical Reasoning When Encountering Virtual
Patients.
AB - BACKGROUND: Training with virtual patients has been proposed as a suitable
learning activity to improve clinical reasoning skills for nursing students.
However, published instruments with the capacity to assess students' reasoning
process in the encounter with virtual patients are lacking. METHOD: Deductive and
abductive analyses were used to adapt the Lasater Clinical Judgment Rubric (LCJR)
to assess nursing students' clinical reasoning skills in the encounter with
virtual patients. The new rubric's ability to capture nursing students' clinical
reasoning processes was tested using deductive analysis and statistical analysis.
RESULTS: A grading rubric for virtual patients, the vpLCJR, was developed.
Cronbach's alpha showed .892, indicating good internal consistency. CONCLUSION:
The rubric vpLCJR, which deconstructs aspects of clinical reasoning for both
students and faculty members, can be used to clarify expectations, assess
students' clinical reasoning process, and provide feedback for learning when
nursing students encounter virtual patients. [J Nurs Educ. 2018;57(7):408-415.].
PMID- 29958311
TI - Programmatic Evaluation of Holistic Admissions: The Influence on Students.
AB - BACKGROUND: Traditional nursing admission processes may pose barriers to
enhancing the diversity of the nursing workforce. Holistic admission moves beyond
academic metrics to include applicants' experiences, attributes, and abilities.
METHOD: Demographic and academic information was examined for students admitted
to a Bachelor of Science in Nursing program before and after holistic admission
implementation, and a survey was completed by students admitted in 2014 through
holistic admission. RESULTS: The admission of Hispanic students significantly
increased, whereas admissions of non-Hispanic White students significantly
decreased. Academic metrics did not change significantly. Students rated the
holistic admission process positively, with the interview rated as more valuable
than the written application. Some students believed it could have a negative
effect on students who were not racial or ethnic minorities. CONCLUSION: Holistic
admission may increase the diversity of a nursing class; however, it should be
combined with other strategies to build a diverse pipeline. [J Nurs Educ.
2018;57(7):416-421.].
PMID- 29958312
TI - Exploring the Student Peer Mentor's Experience in a Nursing Peer Mentorship
Program.
AB - BACKGROUND: The mentor's role is often underreported in the literature. Given the
pivotal role peer mentors play in mentorship efforts, the current study sought to
explore the experiences and perceptions of peer mentors enrolled in a university
affiliated, nursing student, peer mentorship program. METHOD: A qualitative
descriptive design was conducted using purposive and snowball sampling
techniques. A one-time interview was conducted with participants using a
semistructured interview guide. Inductive thematic content analysis occurred
concurrently with data collection. RESULTS: Eight mentors participated revealing
four major themes: Doing What I Wish Someone Had Done for Me, Initial Face-to
Face Contact Is Key, Being Thrown to the Wind, and Practicing What I Will Use as
a Nurse. CONCLUSION: Aspects of self-directed learning may benefit future careers
for student peer mentors. Opportunities for program enhancement include coping
and communication skills for peer mentors. Future "scaled-up" evaluations are
needed for ongoing quality improvements using multimethod approaches. [J Nurs
Educ. 2018;57(7):422-425.].
PMID- 29958313
TI - Development and Assessment of an Interprofessional Education Simulation to
Promote Collaborative Learning and Practice.
AB - BACKGROUND: We designed an interprofessional education (IPE) clinical simulation
that paired nurse practitioner and pharmacy students. The objective was to
evaluate the effect on attitudes of interprofessional collaborative learning and
practice. METHOD: Perceptions were assessed using the Student Perceptions of
Interprofessional Clinical Education-Revised instrument and reflection questions
that assessed the simulation's effectiveness in requiring team knowledge and
experience from each profession whether the experience improved individual
student clinical performance, and how this team approach influenced patient
outcomes. RESULTS: Students believed that working with another health profession
was educationally beneficial and should be a required experience; they also
believed that this collaboration improved patient outcomes and satisfaction.
Responses also indicated student ambiguity about their role in interprofessional
care, and that clinical rotations were not the ideal setting for first
professional interactions with others. CONCLUSION: Students expressed
satisfaction and increased awareness of the importance of collaboration to ensure
patient safety. Increasing interprofessional education experiences prior to
clinical rotations should be considered. [J Nurs Educ. 2018;57(7):426-429.].
PMID- 29958314
TI - Developing a Culture of Caring and Support Through a Peer Mentorship Program.
AB - BACKGROUND: Academic leaders are concerned about the retention rate of nursing
students; peer mentoring may be one strategy for student success. Research
studies on mentoring indicate the benefits of mentoring accrue for both mentors
and mentees. METHOD: A peer voluntary mentorship program operated in coordination
with an academic resource center for a decade. It included training and weekly
meetings. Mentors were senior nursing students who had a minimum B+ average and
faculty recommendations. All mentors kept journal logs of their time and
reflections of their experience. RESULTS: Journal statements revealed that
mentored nursing students felt more successful in their coursework, gained test
taking skills, and did better on examinations. Mentors gained confidence about
their skills and were better prepared for the NCLEX. Mentees formed a natural
support group. Mentors expressed concern about their students' success beyond the
program. CONCLUSION: This program generated a culture of caring and support to
the nursing students, with the understanding that they would give back to others
what they had received. [J Nurs Educ. 2018;57(7):430-435.].
PMID- 29958315
TI - Service-Learning: Promoting Empathy Through the Point-in-Time Count of Homeless
Populations.
AB - BACKGROUND: An interprofessional service-learning experience, using the U.S.
Department of Housing and Urban Development Point-in-Time (PIT) count of
unsheltered homeless, was used as the basis of exposing nursing and public health
students to those facing homelessness and housing insecurity in their community.
METHOD: Learning experiences included pre- and post-PIT count training, PIT count
participation, debriefings, online and in-class reflections, and discussion of
poverty-related readings. Students unable to participate in the actual count
presented nutrition education programs in congregate meal sites. RESULTS:
Participation in the PIT count received positive student feedback and reflected
development of knowledge and empathy of those experiencing homelessness and
housing and food insecurity. CONCLUSION: Health professional programs can use the
PIT count to expose students to individuals living in poverty, as well as provide
meaningful curricular opportunities to foster a culturally competent and
empathetic health services work force. [J Nurs Educ. 2018;57(7):436-439.].
PMID- 29958316
TI - Master of Science in Nursing and Doctor of Nursing Practice Clinical Curriculum
Map.
AB - BACKGROUND: The development of a comprehensive and structured clinical curriculum
map can outline the specific content covered throughout a nurse practitioner
program and provide a method for identifying redundancy and omissions in the
didactic clinical content. METHOD: A curriculum map outlining the specific
clinical content covered in each didactic course in a Master of Science in
Nursing and Doctor of Nursing Practice advanced practice program was created. The
curriculum map incorporated accreditation standards, certification testing
domains, and common primary care diagnoses. RESULTS: A curriculum map supported
the development of organized, consistent, and transparent clinical didactic
content across courses and the program. The curriculum map allows for frequent
curriculum and course review and updates to help meet program and accreditation
standards. CONCLUSION: The development and implementation of the clinical
didactic curriculum map facilitates the integration of core clinical content in
an organized manner that builds learning and prepares future nurse practitioners.
[J Nurs Educ. 2018;57(7):440-445.].
PMID- 29958318
TI - Nursing Students Choose Their Own Role in a Flipped Classroom Approach.
PMID- 29958317
TI - Interrater Reliability and Usability of a Nurse Anesthesia Clinical Evaluation
Instrument.
AB - BACKGROUND: No Student Registered Nurse Anesthetist (SRNA) clinical evaluation
instrument (CEI) has undergone interrater reliability or usability testing, to
the authors' knowledge. This project determined the interrater reliability and
usability of a new SRNA CEI. METHOD: This was a prospective, mixed qualitative
and quantitative, fully crossed observational design with a usability survey.
SRNAs' recorded performance during simulation was evaluated by participants, who
also completed a usability survey. RESULTS: Interrater reliability is high,
intraclass correlation coefficient = .982, 95% CI [.884, .960], indicating strong
agreement of SRNA clinical performance among participants (n = 10). Internal
consistency is excellent (Cronbach's alpha = .943), indicating the CEI is
constructed appropriately and participants found it easy to use. CONCLUSION: This
CEI may advance the aim of impartiality in the evaluation of SRNA clinical
performance through an instrument that is reliable, with good construct, and ease
of use. [J Nurs Educ. 2018;57(7):446-449.].
PMID- 29958319
TI - Engaging Undergraduate Nursing Students With Barcode Scanning in an Oncology
Course.
PMID- 29958320
TI - Advancing Risk-Informed Decision Making in Managing Defense Nuclear Waste in the
United States: Opportunities and Challenges for Risk Analysis.
AB - An omnibus spending bill in 2014 directed the Department of Energy to analyze how
effectively Department of Energy (DOE) identifies, programs, and executes its
plans to address public health and safety risks that remain as part of DOE's
remaining environmental cleanup liabilities. A committee identified two dozen
issues and associated recommendations for the DOE, other federal agencies, and
the U.S. Congress to consider, as well as other stakeholders such as states and
tribal nations. In regard to risk assessment, the committee described a risk
review process that uses available data, expert experience, identifies major data
gaps, permits input from key stakeholders, and creates an ordered set of risks
based on what is known. Probabilistic risk assessments could be a follow-up from
these risk reviews. In regard to risk management, the states, in particular, have
become major drivers of how resources are driven. States use different laws,
different priorities, and challenge DOE's policies in different ways. Land use
decisions vary, technology choices are different, and other notable variations
are apparent. The cost differences associated with these differences are marked.
The net result is that resources do not necessarily go to the most prominent
human health and safety risks, as seen from the national level.
PMID- 29958321
TI - The association between peer network centrality and aggression is moderated by
moral disengagement.
AB - There is very little research on the dynamics of peer groups in schools and
aggressive behavior among Chinese youth. In the present study, we investigated
the link between pure indegree centrality and aggression (i.e., overt and
relational aggression), and examined moderating effects of moral disengagement on
this association, among Chinese adolescents in classes with different percentage
of aggressors. Participants were 589 sophomore students (446 boys, 75.72% of
sample; Mage = 15.98, SD = 0.64) from 16 classes in one vocational secondary
school. The results showed that the effects for overt and relational aggression
were moderated by the proportion of aggressors within classes and moral
disengagement. For students in classes with a higher density of aggressors, there
was a strong positive association between pure indegree centrality and overt
aggression (but not relational aggression) for those students with higher moral
disengagement. Conversely, in classes with fewer aggressive students, the
covariation between centrality and both overt and relational aggression was
negative for students with higher moral disengagement. These findings are
consistent with an ecological perspective on the development of aggression, which
shows that aggregating aggressive students in school classes may strengthen the
associations between peer dynamics, moral disengagement, and aggressive behavior.
PMID- 29958322
TI - Burnout-depression overlap: Nomological network examination and factor-analytic
approach.
AB - Burnout has been defined as a condition in which individuals are left exhausted
by a long-term confrontation with unmanageable job stressors. The question of
whether burnout reflects anything other than depressive responses to unresolvable
stress remains an object of debate. In this 911-participant study (83% female;
mean age: 42.36), we further addressed the issue of burnout-depression overlap.
Burnout was assessed with the exhaustion subscale of the Maslach Burnout
Inventory-General Survey (MBI-GS) and depression with the PHQ-8. The
relationships of burnout and depression with three job-related variables -
illegitimate work tasks, work-nonwork interference, and job satisfaction - and
three "context-free" variables - social support, general health status, and trait
anxiety - were examined. Burnout and depression were found to be strongly
correlated, to cluster together, and to exhibit overlapping nomological networks.
Remarkably, the average correlations of burnout and depression with job-related
variables were almost identical. A principal component analysis and a principal
axis factor analysis both showed that the items of the MBI-GS and of the PHQ-8
loaded on a single dimension. All in all, our findings are consistent with the
view that burnout is a depressive condition. The distinction between burnout and
depression may be an instance of the jangle fallacy.
PMID- 29958323
TI - How a terror attack affects right-wing authoritarianism, social dominance
orientation, and their relationship to torture attitudes.
AB - Self-reported level of right-wing authoritarianism (RWA), the two facets of
social dominance orientation (SDO-Dominance and SDO-Egalitarianism) and pro
torture attitudes were measured both in the immediate aftermath (terror salience,
N = 152) of the terror attacks in Paris and Brussels and when terrorism was not
salient (non-salience, N = 140). Results showed that RWA and pro-torture
attitudes, but not SDO-Dominance and SDO-Egalitarianism, were significantly
higher immediately after. Furthermore, RWA and SDO both predicted pro-torture
attitudes more strongly under terror salience. We argue that the reason why RWA
is higher under terror salience is a response to external threat, and that SDO
Dominance may be more clearly related to acceptance of torture and other human
rights violations, across context. Future research on the effects of terror
related events on sociopolitical and pro-torture attitudes should focus on person
situation interactions and also attempt to discriminate between trait and state
aspects of authoritarianism.
PMID- 29958324
TI - Antimicrobial activity of amixicile against Treponema denticola and other oral
spirochetes associated with periodontal disease.
AB - BACKGROUND: Periodontal disease is a polymicrobial infection characterized by
inflammation of the gingiva, alveolar bone resorption and tooth loss. As
periodontal disease progresses, oral treponemes (spirochetes) become dominant
bacteria in periodontal pockets. Oral treponemes are anaerobes and all encode the
enzyme pyruvate-ferredoxin oxidoreductase (PFOR) which catalyzes the oxidative
decarboxylation of pyruvate to acetyl-CoA. Here we assess the susceptibility of
oral treponemes to amixicile (AMIX), a novel inhibitor of PFOR. METHODS: The
minimum inhibitory concentration (MIC) of AMIX against several oral treponeme
species was determined. The impact of AMIX on processes relevant to virulence
including motility, H2 S production, and complement evasion were determined.
RESULTS: The growth of all oral treponeme species tested was inhibited by AMIX
with MIC concentrations (MIC) ranging from 0.5-1.5 MUg/mL. AMIX significantly
reduced motility, caused a dose-dependent decrease in hydrogen sulfide production
and increased sensitivity to killing by human complement (i.e., serum
sensitivity). CONCLUSIONS: AMIX is effective in vitro in inhibiting growth and
other processes central to virulence. AMIX could serve could serve as a new
selective therapeutic tool for the treatment of periodontal disease.
PMID- 29958325
TI - Indirect effects of parental and peer attachment on bullying and victimization
among adolescents: The role of negative automatic thoughts.
AB - The association between parental and peer attachment and youths' bullying
involvement is well documented. However, there is little research examining
mechanisms linking the quality of relationships with parents and peers to
bullying perpetration and victimization. The present study investigated the
indirect effects of attachment to the mother, the father, and peers on bullying
and victimization through children's negative automatic thoughts in a sample of
476 adolescents (10-17 years). Path analysis indicated that attachment to both
parents as well as attachment to peers was indirectly related to both bullying
and victimization through their relationship with adolescents' negative automatic
thoughts. When particular cognitive contents of negative automatic thoughts were
examined, only hostile thoughts emerged as a mechanism explaining the association
between poor relationships with parents and peers and bullying involvement as
perpetrator, whereas poor attachment with each socialization agent had an
indirect effect on bullying victimization via hostility and social threat
thoughts.
PMID- 29958326
TI - Interdependent Sequence Selectivity and Diastereoselectivity in the Alkylation of
DNA by Decarbamoylmitomycin C.
AB - Mitomycin C (MC), an antitumor drug, and decarbamoylmitomycin C (DMC), a
derivative of MC, alkylate DNA and form deoxyguanosine monoadducts and
interstrand crosslinks (ICLs). Interestingly, in mammalian culture cells, MC
forms primarily deoxyguanosine adducts with a 1"-R stereochemistry at the guanine
mitosene bond (1"-alpha) whereas DMC forms mainly adducts with a 1"-S
stereochemistry (1"-beta). The molecular basis for the stereochemical
configuration exhibited by DMC has been investigated using biomimetic synthesis.
Here, we present the results of our studies on the monoalkylation of DNA by DMC.
We show that the formation of 1"-beta-deoxyguanosine adducts requires
bifunctional reductive activation of DMC, and that monofunctional activation only
produces 1"-alpha-adducts. The stereochemistry of the deoxyguanosine adducts
formed is also dependent on the regioselectivity of DNA alkylation and on the
overall DNA CG content. Additionally, we found that temperature plays a
determinant role in the regioselectivity of duplex DNA alkylation by mitomycins:
At 0 degrees C, both deoxyadenosine (dA) and deoxyguanosine (dG) alkylation
occur whereas at 37 degrees C, mitomycins alkylate dG preferentially. The new
reaction protocols developed in our laboratory to investigate DMC-DNA alkylation
raise the possibility that oligonucleotides containing DMC 1"-beta-deoxyguanosine
adducts at a specific site may be synthesized by a biomimetic approach.
PMID- 29958328
TI - Cross-sectional association of physical activity and periodontal antibodies.
AB - BACKGROUND: The objective of this study was to evaluate the cross-sectional
association between physical activity and serum IgG antibodies against selected
periodontal microorganisms. METHODS: The study population consisted of 5,611
randomly selected US adults who participated in the National Health and Nutrition
Examination Survey (NHANES) III (1988 to 1994), who were 40 years and older with
complete IgG antibody data against 19 oral microorganisms. We used cluster
analysis to classify the 19 antibody titers into 4 mutually exclusive groups
called "Orange-Red," "Red-Green," "Yellow- Orange," and "Orange-Blue," and
calculated cluster scores by summing antibody titer z-scores for each of the four
groups. Physical activity was evaluated based on reported frequency and intensity
of physical activity conducted in the last month. Participants were grouped into
three categories: adequately physically active, inadequately physically active,
and inactive. The outcomes were IgG cluster scores with physical activity as the
predictor. Multivariable models adjusted for age, sex, race, smoking status,
waist circumference, education, poverty-income-ratio, alcohol, and diabetes.
RESULTS: In adjusted models, physical activity was positively associated with the
antibodies in the Orange-Blue cluster (E. nodatum, A. naeslundii), a cluster that
is associated with healthy periodontal states. The mean differences in cluster
scores were 15.2 (95% CI -1.0, 31.4) for Model 3, and 7.0 (95% CI -8.3, 22.3) for
Model 4 comparing the sufficiently active group to the inactive group.
CONCLUSIONS: Antibody titers against periodontal microorganisms reflecting good
oral health trended higher among physically active individuals, but the results
were not statistically significant at the 0.05 level.
PMID- 29958327
TI - Platelet-rich fibrin/biphasic calcium phosphate impairs osteoclasts
differentiation and promotes apoptosis by the intrinsic mitochondrial pathway in
chronic periodontitis.
AB - BACKGROUND: The study explored the effect of platelet-rich fibrin/biphasic
calcium phosphate (PRF/BCP) on differentiation and survival of osteoclasts
obtained from peripheral blood of CP patients. METHODS: Peripheral blood
mononuclear cells (PBMCs) from 25 patients with chronic periodontitis (CP) and 25
healthy individuals were assayed for cluster of differentiation14+ (CD14+ )
expression and monocytes were induced to differentiate into osteoclasts for 21
days in-vitro in the presence of macrophage colony stimulating factor (M-CSF) and
receptor activator of nuclear factor-kappa B ligand (RANKL). We assessed the
number of osteoclasts by tartrate-acid resistant acid phosphatase (TRAP)
positivity. The mechanism of apoptosis was studied with reference to expression
of Bcl-2, Bax, Bcl-xL, nuclear factor kappa-light chain enhancer of activated B
cells (NF-kappaB), caspase 3/9 and DNA fragmentation. RESULTS: We observed a
relative increase in the proportion of circulating osteoclasts in test group than
control group (healthy individuals). In addition, osteoclast precursors in
untreated cells (CP) were more osteoclastogenic as compared to cells treated with
PRF/BCP and hence, there was a significant increase in the number of osteoclasts
in CP. In PRF/BCP treated cells, we found a direct inhibition of transcription
factor NF-kappaB with an increased caspase 3/9 levels and caspase 3 activity.
Additionally, the protein expression and transcriptional profile of Bax was
upregulated and Bcl-2 and Bcl-xL levels were down-regulated on treatment with
PRF/BCP. CONCLUSION: Our results revealed that the PRF/BCP displayed an
inhibitory role in osteoclasts formation and its molecular mechanism of action
was related to the apoptosis induction through intrinsic mitochondrial pathway.
PMID- 29958329
TI - Comparison of orofacial thermal sensitivity assessed with simple devices and
sophisticated equipment.
AB - BACKGROUND: Simple thermal devices providing reliable data are needed to detect
somatosensory disturbances in non-specialized clinical settings. Currently,
evidence is lacking about their use. Therefore, the aim was to compare the
assessment of perceived thermal sensitivity/pain in healthy humans with a state
of-the-art thermotester and with simple inexpensive customized thermal aluminium
devices. METHODS: Twenty healthy volunteers participated in the study. The
infraorbital region and the tip of the tongue were tested with the Medoc Pathway
thermotester and simple aluminium thermal devices, with temperatures varying
between 5-50 degrees C. A numerical rating scale (NRS) from 0-50-100 was used for
rating the perceived thermal sensitivity/painfulness. A control experiment was
performed with 10 of the participants to test the potential impact of temporal
summation of thermal stimuli with the use of temperature ramps (Medoc) compared
with static temperature (simple devices). RESULTS: In the original experiment,
the scores from the thermotester stimulation were higher than the scores for
stimulation with the simple thermal devices with mean NRS differences between
devices of 7.2 and 10.2 for the two tested regions. In the control experiment,
the mean NRS differences decreased to -0.3 and 2.2, respectively. CONCLUSIONS:
Provided that temporal summation of the thermal stimuli was avoided, there were
only minor differences in perceived thermal sensitivity/painfulness between the
two different assessment methods at both test sites. Therefore, the simple
thermal devices can be useful for assessment of thermal sensitivity in clinical
settings without access to expensive sophisticated equipment. However, more
sophisticated equipment is needed for threshold measurements. SIGNIFICANCE: This
study indicates that simple thermal devices to some extent can be used in a
comparable way with sophisticated thermal stimulators. Therefore, they can be
useful in clinical practice, where access to further equipment is lacking.
PMID- 29958330
TI - Evolution of Research Ethics in a Low Resource Setting: The Case of Uganda.
AB - BACKGROUND: The globalization of clinical research in the last two decades has
led to a significant increase in the volume of clinical research in developing
countries. As of 2016, Uganda was the third largest destination for clinical
trials in Africa. This requires adequate capacity and systems to facilitate
ethical practice. METHODS: This was a retrospective study involving review of
laws, guidelines, policies and records from 1896 to date. RESULTS: Modern
medicine evolved from 1896 and by the time of Uganda's independence in 1962, a
1500 bed national referral hospital was in place and a fully-fledged medical
school was established at the Makerere University. As the practice of medicine
evolved in the country, so did medical research that addressed priority health
issues. The growth in modern medicine was not matched with development of
research infrastructure and regulatory systems. The first documented regulation
of research activities was in 1970 while the first research ethics committee
established in 1986 was to facilitate review of research related to the HIV/AIDs
pandemic. In 1990 an Act of Parliament was passed to facilitate development and
implementation of policies, hence the development of the national guidelines in
1997, training, establishment and accreditation of research ethics committees,
conferences and research site monitoring. CONCLUSION: Over the past 120 years,
the implementation and structural aspects of research ethics in Uganda have
evolved through 70 years of no regulation, followed by 30 years of rudimentary
regulation while the last 20 years have shown significant growth in the
regulatory system associated with supportive laws, institutionalization of
regulatory and training processes.
PMID- 29958331
TI - Superprotonic Conductivity in Flexible Porous Covalent Organic Framework
Membranes.
AB - Poor mechanical stability of the polymer electrolyte membranes remains one of the
bottlenecks towards improving the performance of the proton exchange membrane
(PEM) fuel cells. The present work proposes a unique way to utilize crystalline
covalent organic frameworks (COFs) as a self-standing, highly flexible membrane
to further boost the mechanical stability of the material without compromising
its innate structural characteristics. The as-synthesized p-toluene sulfonic acid
loaded COF membranes (COFMs) show the highest proton conductivity (as high as
7.8*10-2 S cm-1 ) amongst all crystalline porous organic polymeric materials
reported to date, and were tested under real PEM operating conditions to
ascertain their practical utilization as proton exchange membranes. Attainment of
24 mW cm-2 power density, which is the highest among COFs and MOFs, highlights
the possibility of using a COF membrane over the other state-of-the-art
crystalline porous polymeric materials reported to date.
PMID- 29958332
TI - Renewable Isohexide-Based, Hydrolytically Degradable Poly(silyl ether)s with High
Thermal Stability.
AB - Several degradable poly(silyl ether)s (PSEs) have been synthesized by
dehydrogenative cross-coupling between bio-based 1,4:3,6-dianhydrohexitols
(isosorbide and isomannide) and commercially available hydrosilanes. An air
stable manganese salen nitrido complex [MnV N(salen-3,5-tBu2 )] was employed as
the catalyst. High-molecular-weight polymer was obtained from isosorbide and
diphenylsilane (Mn up to 17000 g mol-1 ). Thermal analysis showed that these PSEs
possessed high thermal stability with thermal decomposition temperatures (T-5 % )
of 347-446 degrees C and glass transition temperatures of 42-120 degrees C.
Structure-property analysis suggested that steric bulk and molecular weight have
a significant influence to determine the thermal properties of synthesized
polymers. Importantly, these polymers were degraded effectively to small
molecules under acidic and basic hydrolysis conditions.
PMID- 29958333
TI - Resolution of Viable and Membrane-Compromised Free Bacteria in Aquatic
Environments by Flow Cytometry.
AB - In aquatic environments, free heterotrophic bacteria play an extremely important
role due to their high biomass, wide panel of metabolisms, and ubiquity, as well
as the toxicity of certain species. This unit presents a nucleic-acid double
staining protocol (NADS) for flow cytometry that can distinguish fractions of
viable, damaged, or membrane-compromised cells within the free-bacterial
community. The NADS protocol is based on the simultaneous utilization of two
nucleic acid stains-membrane-permeant SYBR Green and membrane-impermeant
propidium iodide (PI). The efficiency of the double staining on fresh samples is
magnified by the FRET from SYBR Green to PI when both are bound to the nucleic
acids. Full quenching of SYBR Green fluorescence by PI identifies cells with a
compromised membrane, partial quenching indicates cells with a slightly damaged
membrane, and lack of quenching characterizes cells with an intact membrane.
Samples do not require any pretreatment and this protocol can be performed almost
anywhere. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29958334
TI - The Effect of Employment Status in Postdisaster Recovery: A Longitudinal
Comparative Study Among Employed and Unemployed Affected Residents.
AB - Population studies have shown that employed adults are healthier than unemployed
adults. In this study, we examined whether this "healthy worker effect" is
relevant in postdisaster mental health by examining whether trauma-exposed
employed individuals have lower postdisaster initial mental health problems
and/or whether they recover faster than trauma-exposed unemployed individuals. We
compared the course of postevent intrusion and avoidance reactions, anxiety,
depression, and sleeping difficulties of employed residents (n = 291) and
unemployed residents (n = 269) affected by a fireworks disaster in a residential
area of Enschede, The Netherlands. Measurements took place at 2-3 weeks (T1), 18
months (T2), and 4 years (T3) postdisaster. We used linear mixed-effect models to
examine the course of mental health problems. Employment status was relevant, to
a degree, in posttrauma recovery; although affected employed residents had
significantly lower levels of mental health problems (initially and over time)
than the unemployed, ds = 0.41-0.72, the recovery rate was the same for both
groups. At T1 (neglecting the DSM 1-month criterion), T2, and T3, the prevalence
of probable posttraumatic stress disorder was 45.4%, 18.9%, and 11%,
respectively, among employed individuals, and 70.1%, 32.5%, and 30% among
unemployed individuals. We concluded that research into the mental health of
disaster victims should take employment status into account. Regarding
postdisaster care, unemployed individuals may need special attention; although
they may recover at the same rate as employed individuals, they suffer from more
severe mental health problems, even years after the disaster.
PMID- 29958335
TI - Trajectories of Psychological Distress in Australians Living in Urban Poverty:
The Impact of Interpersonal Trauma.
AB - Childhood maltreatment and interpersonal trauma experience is an important factor
underpinning the apparent perpetuation of the cycle of social disadvantage
experienced by homeless adults. This paper aimed to examine longitudinal patterns
of psychological distress in a sample of 1,504 socially disadvantaged adult
participants from the Journeys Home Study in Australia. The current paper
utilized the "conservation of resources" theory and the concept of "risk factor
caravans" to investigate the nature and implications of childhood trauma in the
context of homelessness. Growth mixture modeling revealed four distinct
trajectories of psychological distress as measured by the Kessler 6 across six
time points (covering a period of 2.5 years): chronic, escalating, attenuating,
and resistant. Our results also indicated that experiences of different types of
trauma during childhood were associated with these psychological distress
trajectories. In particular, adults experiencing chronic psychological distress
were significantly more likely than those exhibiting distress resistance to have
experienced multiple and varied childhood maltreatment, adjusted odds ratio (AOR)
= 3.30, 95% CI [0.37, 6.05], p = .002. Furthermore, adult experiences of assault
were found to be associated with psychological distress. These findings have
important implications for mental health, as well as interventions aimed at
breaking the cycle of urban poverty. Specific focus on interpersonal trauma
vulnerabilities is important. Prioritizing socioecological stability, with mental
health needs assessed on an individual level, may be most appropriate. This work
also highlights the need to direct future attention to barriers to access and
facilitation of social support services.
PMID- 29958336
TI - A Systematic Review of Psychological and Pharmacological Treatments for
Adjustment Disorder in Adults.
AB - Adjustment disorder is a common psychiatric disorder, yet knowledge of the
efficacious treatments for adjustment disorder is limited. In this systematic
review, we aimed to examine psychological and pharmacological interventions that
target adjustment disorder in adults to determine which interventions have the
best evidence for improving adjustment disorder symptoms. We performed database
searches for literature published between January 1980 and September 2016 and
identified studies that included both a sample majority of individuals diagnosed
with adjustment disorder and findings on adjustment disorder symptom outcomes.
There were 29 studies that met the inclusion criteria for qualitative synthesis;
the majority of studies (59%) investigated psychological therapies rather than
pharmacological treatments (35%). The range of psychological therapies tested was
diverse, with the majority containing cognitive behavioral therapy (CBT)
components (53%), followed by three studies that were psychodynamic-related,
three studies that were behavioral therapy-based, and two studies that involved
relaxation techniques. We rated individual studies using a modified National
Health and Medical Research Council quality and bias checklist and then used the
Grading of Recommendations Assessment, Development and Evaluation (GRADE; Grade
Working Group, 2004) system to rate the overall quality of the evidence. Despite
several randomized controlled trials, the quality of the evidence for positive
effects of all psychological and pharmacological treatments on symptoms of
adjustment disorder was ranked as low to very low. Future high-quality research
in the treatment of adjustment disorder has the potential to make a significant
difference to individuals who struggle to recover after stressful events.
PMID- 29958337
TI - Treatment Outcomes for Military Veterans With Posttraumatic Stress Disorder:
Response Trajectories by Symptom Cluster.
AB - Although effective posttraumatic stress disorder (PTSD) treatments are available,
outcomes for veterans with PTSD are relatively modest. Previous researchers have
identified subgroups of veterans with different response trajectories but have
not investigated whether PTSD symptom clusters (based on a four-factor model)
have different patterns of response to treatment. The importance of this lies in
the potential to increase treatment focus on less responsive symptoms. We
investigated treatment outcomes by symptom cluster for 2,685 Australian veterans
with PTSD. We used Posttraumatic Stress Disorder Checklist scores obtained at
treatment intake, posttreatment, and 3- and 9-month follow-ups to define change
across symptom clusters. Repeated measures effect sizes indicated that arousal
and numbing symptoms exhibited the largest changes between intake and
posttreatment, dRM = -0.61 and dRM = -0.52, respectively, whereas avoidance and
intrusion symptoms showed more modest reductions, dRM = -0.36 and dRM = -0.30,
respectively. However, unlike the other symptom clusters, the intrusions cluster
continued to show significant changes between posttreatment and 3-month follow
up, dRM = -0.21. Intrusion and arousal symptoms also showed continued changes
between 3- and 9-month follow-ups although these effects were very small, dRM =
0.09. Growth curve model analyses produced consistent findings and indicated
modest initial changes in intrusion symptoms that continued posttreatment. These
findings may reflect the longer time required for emotional processing, relative
to behavioral changes in avoidance, numbing, and arousal, during the program;
they also reinforce the importance of prioritizing individual trauma-focused
therapy directly targeting intrusions as the core component of programmatic
treatment.
PMID- 29958338
TI - Dimensions of Growth? Examining the Distinctiveness of the Five Factors of the
Posttraumatic Growth Inventory.
AB - Posttraumatic growth, defined as positive transformation following trauma, is
commonly measured using the Posttraumatic Growth Inventory (PTGI; Tedeschi &
Calhoun, 1996) and is postulated to comprise five distinct domains: Changes in
Relationships, Life Possibilities, Personal Strength, Spirituality, and
Appreciation of Life. However, research has indicated that the model fit is not
good and the factors are highly intercorrelated. Further, no studies have
formally examined the heterogeneity of correlations of the five factors with
external constructs. In an effort to examine the construct validity of the five
factor model of the PTGI, the present study aimed to examine the degree to which
the theorized five factors demonstrate meaningful differential associations with
relevant external correlates. Participants were 400 undergraduate students who
reported having experienced a stressful event and completed the Life Events
Checklist for DSM-5, PTGI, Posttraumatic Stress Disorder Checklist for DSM-5,
Grit Scale-12, Connor-Davidson Resilience Scale-10, and Work and Social
Adjustment Scale. We found few instances of significant differentiation, and
effect sizes for pairwise comparisons were generally small, Cohen's qs = 0.01
0.35. Although factor analytic evidence suggests there are five distinct
underlying constructs, our results indicated that these factors do not
significantly differ in their associations with external correlates. Implications
for use of the PTGI and future research directions are discussed.
PMID- 29958339
TI - Effects of existential interventions on spiritual, psychological, and physical
well-being in adult patients with cancer: Systematic review and meta-analysis of
randomized controlled trials.
AB - OBJECTIVES: To synthesize the evidence of existential interventions in adult
patients with cancer. METHODS: Embase, MEDLINE, CENTRAL, CINAHL, PsycINFO,
PSYNDEX, and the WHO ICTRP were searched up until 26 January 2018. Eligibility
criteria for studies were (1) adult patients with cancer, (2) evaluation of
existential interventions, (3) compared with active/non-active control, (4)
assessing relevant spiritual, psychological, or physical outcomes, and (5)
conducted as randomized controlled trials. Standardized mean differences (Hedges'
g) were calculated, and meta-analyses were conducted using random effects models.
Effects were aggregated within four time horizons (post-treatment; <=3 months;
<=6 months; >6 months). Heterogeneity was assessed by forest plots and I2 . Risk
of bias was assessed using the Cochrane Risk of Bias Tool. This review has been
registered with Prospero (CRD42016042895). RESULTS: A total of 3461 records were
identified, of which 30 unique studies (3511 participants) were included in the
review and 24 studies were included in meta-analyses. Existential interventions
showed significant effects on existential well-being (g = 0.52; CI[0.13; 0.91; k
= 10; I2 = 85%) and quality of life (g = 0.21; CI[0.01; 0.42]; k = 17; I2 =
75%) at post-treatment, on hope at post-treatment (g = 0.43; CI[0.12; 0.74]; k =
12; I2 = 86%) and after 6 months (g = 0.25; CI[0.02; 0.48]; k = 3; I2 = 0%) and
on self-efficacy at post-treatment (g = 0.50; CI[0.09; 0.90]; k = 2; I2 = 0%).
No significant effects were found on the remaining outcomes and time points.
Significant moderator effects were found for professional background of
therapists, intervention concept, number of sessions, and setting. CONCLUSIONS:
This systematic review and meta-analysis provides evidence that adult patients
with cancer across all stages and types benefit from existential interventions.
Future research should strive towards a higher standardization in particular with
respect to outcome assessments.
PMID- 29958340
TI - Language brokering in multilingual caregiving settings.
AB - Using the methodology of conversation analysis to examine audio-recorded multi
party conversations between a Swedish-/Farsi-speaking resident and multilingual
staff in a Swedish residential home, this article describes a practice for
establishing shared understanding by one caregiver enacting the role of language
broker. The focus is on caregiving settings where caregivers assist an elderly
person with her personal hygiene. We demonstrate how brokering is used to (1)
maintain the conversational flow in a small talk sequence and (2) address the
contents in the resident's complaints. The article thus advances our
understanding of language brokering as an activity that multilingual staff in a
linguistically asymmetrical workplace setting take on to assist a colleague in
performing client-oriented activities.
PMID- 29958341
TI - Mitigation of claims in medical research papers: A comparative study of English-
and Spanish-language writers.
AB - This study identifies variation in the use of mitigation devices in medical
written English between authors with English as their first language and those
with Spanish as their first language. A corpus of 30 medical research papers
written in English and published in international journals was compiled, 15 by
researchers with Spanish as their first language and 15 by native English
speakers, and this was compared with a second corpus of 15 medical papers written
in Spanish. By a comparative analysis of how mitigation devices were used in both
corpora, it was possible to establish whether their frequency and the rhetorical
strategies adopted varied depending on the writer's linguistic background.
PMID- 29958342
TI - 'Are we on the same wavelength?' International nurses and the process of
confronting and adjusting to clinical communication in Australia.
AB - Effective communication skills are important in the health care setting in order
to develop rapport and trust with patients, provide reassurance, assess patients
effectively and provide education in a way that patients easily understand
(Candlin and Candlin, 2003). However with many nurses from culturally and
linguistically diverse (CALD) backgrounds being recruited to fill the workforce
shortfall in Australia, communication across cultures with the potential for
miscommunication and ensuing risks to patient safety has gained increasing focus
in recent years (Shakya and Horsefall, 2000; Chiang and Crickmore, 2009). This
paper reports on the first phase of a study that examines intercultural nurse
patient communication from the perspective of four Registered Nurses from CALD
backgrounds working in Australia. Five interrelating themes that were derived
from thematic analysis of semi-structured interviews are discussed. The central
theme of 'adjustment' was identified as fundamental to the experiences of the RNs
and this theme interrelated with each of the other themes that emerged:
professional experiences with communication, ways of showing respect, displaying
empathy, and vulnerability.
PMID- 29958343
TI - Modality resources in Spanish during psychiatric interviews with Mexican
patients.
AB - This study examines modality in doctor-patient interactions during psychiatric
interviews. Twenty three interviews were conducted in Spanish and were video
recorded. The patients are members of a small community in rural California.
Using the interpersonal metafunction (Eggins 2004; Halliday 1994) and approaches
in pragmatics literature this work reveals the lexicogrammatical choices the
patients and the doctor make using both qualitative analysis and quantitative
analysis. Spanish modalization can be realized through modal operators (e.g.
might), mood adjuncts (e.g. possibly), and the conditional and future tenses. In
addition to these, oral contexts have alternative forms of expressing
modalization such as using the preposition como 'like' and tag questions (e.g.
right?) as the pragmatics literature has described. This work makes a
methodological contribution by highlighting the analytical tools that alternative
approaches to discourse analysis (pragmatics in this case) make available and how
they complement the interpersonal metafunction. The results of this study reveal
that patients use modalization at particular moments in the interview, for
instance when discussing their symptoms and conditions to deliver their
information carefully and to recognize the social status of the doctor. The
doctor also strategically uses modalization when he asks sensitive questions in
order to displace responsibility from the patients and avoid a face-threatening
situation.
PMID- 29958344
TI - Contrasting discourse styles and barriers to patient participation in bedside
nursing handovers.
AB - This paper applies qualitative discourse analysis to 'shift-change handovers',
events in which nurses hand over care for their patients to their colleagues. To
improve patient safety, satisfaction and inclusion, hospitals increasingly
require nursing staff to hand over at the patient's bedside, rather than in staff
only areas. However, bedside handover is for many a new and challenging
communicative practice. To evaluate how effectively nurses achieve bedside
handover, we observed, audio-recorded and transcribed nursing shift-change
handovers in a short stay medical ward at an Australian public hospital. Drawing
on discourse analysis influenced by systemic functional linguistics we identify
four handover styles: exclusive vs inclusive and objectifying vs agentive. The
styles capture interactional/interpersonal meaning choices associated with
whether and how nurses include patients during handover, and
informational/ideational meaning choices associated with whether or not nurses
select and organise clinical information in ways that recognise patients' agency.
We argue that the co-occurrence of inclusive with agentive and exclusive with
objectifying styles demonstrates that how nurses talk about their patients is
powerfully influenced by whether and how they also talk to them. In noting the
continued dominance of exclusive objectifying styles in handover interactions, we
suggest that institutional change needs to be supported by communication
training.
PMID- 29958345
TI - Pilot evaluation of a novel observational tool for collaboration and
communication within multidisciplinary team meetings (MDTs).
AB - BACKGROUND: Despite widespread use of multidisciplinary team meetings (MDTs) to
facilitate patient care, little evidence exists that MDTs improve patient
survival or impact care. Research into MDT function and outcome is limited. This
pilot study looks to validate a novel tool developed to assess MDT functioning.
METHODS: A tool was developed with predefined Likert behaviour stems in the areas
of structure, communication and collaboration. The tool was evaluated in nine
MDTs by three independent observers and included participant evaluation. Inter
rater reliability was calculated with intraclass-correlation coefficients (ICC);
Student's t-test was used to calculate significance in participant evaluation and
matched observations. RESULTS: The tool was used to evaluate 9 MDTs, discussing
133 cases. The overall ICC for the three coders was 0.935; for each MDT: 0.776
0.917. The inter-rater reliability for each MDT observation ranged from 0.245
0.923; the majority with an ICC >0.8. No significant difference was noted between
participant evaluation and observer response. DISCUSSION: MDTs provide a means of
coordinating complex care for patients. This tool provides a means of evaluating
group interaction within MDTs and is designed for use by different medical
personnel. The pilot study has shown promising ICC; further evaluation is needed
using a broader group of MDTs and including case complexity and outcome.
PMID- 29958346
TI - Analysing teamwork in health care: What matters when clinicians negotiate the
continuity of clinical tasks and care responsibilities?
AB - This paper considers the ways in which clinicians enact 'being a team', by
analysing how they inform one another about critical patient information. The
process where this information exchange happens is known as 'clinical handover'.
The study that informs this paper spanned ten months of data collection in four
hospitals, involving 150 clinicians and five patients. The analysis presented
here draws on data collected at one of the hospital sites: an emergency
department at a regional tertiary teaching hospital. Our analysis reveals how
central clinical handover is to 'being a team' in health care, and how
deficiencies in handover weaken clinical teams' ability to provide continuous and
safe care for their patients. We further discuss how clinical practitioners' own
responses to the footage foregrounded different issues compared to those revealed
by formal analysis; namely, issues centring on relationships, and on practical
steps to ensure these relationships could be improved. We reflect on the
differences between our own formal analysis of the footage, and practitioners'
'lived response' to the footage, and the implications of these differences for
how we as analysts conceptualise 'teamness' in organisations.
PMID- 29958347
TI - Professionals' embodied orientations towards patients in discharge-planning
meetings and their impact on patient participation.
AB - To enhance the patient's involvement, clinical guidelines on rehabilitation
require the patient's participation in the entire rehabilitation process,
including discharge planning (DP). However, very little is known about how this
institutional demand is actually dealt with in everyday clinical practice.
Adopting a conversation analytic (CA) approach, our paper tackles the matter by
looking at interdisciplinary entry meetings (IEMs) at a rehabilitation clinic in
German-speaking Switzerland. Our study is based on audio-visual recordings of 11
IEMs, whose central aim is to formulate patients' rehabilitation goals and to
plan their discharge. The paper offers a detailed analysis of the embodied
practices through which healthcare professionals seek to involve patients in the
IEMs, and also investigates patients' responses. Our analysis shows that,
although carefully elaborated, the professionals' practices do not elicit more
than reactive patient participation. The paper argues that this is due to (1) the
practices' temporal positioning within the overall activity structure of the
meeting - they are deployed when no important decision is at stake, projecting
minimal patient participation on the phases in which decisions are taken - and
(2) the actions the practices project on the next turn: confirmation,
acknowledgement or ratification of what has previously been proposed by
professionals.
PMID- 29958348
TI - Team talk and problem solving in thoracic medicine.
AB - The topic of this article is collaborative problem solving conducted as talk and
social interaction in a particular team in the thoracic ward of a Norwegian
hospital. The problems to be solved were complex and required a team consisting
of participants from diverse medical specialties that met regularly to discuss
examination procedures, formulate diagnoses, and decide forms of treatment. Data
for the article come from field notes and audio recordings made while the author
observed this meeting regularly over more than one year. The aim of the paper is
to investigate how team discourse was regulated in ways that served the
reproduction of institutional medical standards for problem solving, and also how
the meeting had to deal with deviations from institutional standards and
attempted to reproduce a certain form of normative orderliness and interaction
order.
PMID- 29958349
TI - A collective clinical gaze: Negotiating decisions in a surgical ward.
AB - This article explores collaborative aspects of clinical decision-making, based on
a focused ethnography and video recordings of meetings in clinical practices in
two wards for gastro-intestinal diseases at the surgical department of a large
Norwegian university hospital. By studying clinicians' communication during
patient introduction, handling uncertainties and surprises, collecting
information, and negotiating acceptance, we elaborate on how collaborative
teamwork in the hospital ward is developed. Further, by drawing on detailed
studies of meetings, in which patients are not physically represented, we explore
ways in which a 'collective clinical gaze' of each patient is constructed on the
basis of documents, memory, and a consensus-directed discussion among clinicians
who are present. Although electronic patient record systems and the like are
expected to produce firm bases for clinical decision-making, our analysis
suggests that more emphasis should be put on how clinicians in their daily
practice establish collectively based validity of any decision being made.
PMID- 29958350
TI - How language shapes psychiatric case formulation.
AB - The aim of this paper is to describe, analyse, and discuss the process of
formulation in the specific context of mental health (MH). Formulation is a
fundamental element of the work of psychiatrists and other MH clinicians that is
expected to be mastered during training. The literature, however, shows that
formulation is rarely explicitly addressed in the psychiatric curriculum; rather,
it is implicitly developed through modelling, and/or clinical practice. This
paper focuses on case formulation in one MH context in Australia. It tracks the
iterative formulation of one patient in a hospital emergency department. The
analysis uses resources from systemic functional linguistics (SFL) situated
within a broader framework of discourse analysis. It highlights patterns of
lexical relations and nominalisation as well as the range of conjunctions. These
make explicit how the clinicians talk about the patient's illness and shape their
developing understanding into a logical formulation. We see applications of this
work for the training of mental health professionals. These data make explicit
the ways in which the participating clinicians use language in the process of
formulation. By bringing this process to the level of consciousness, it can be
discussed and evaluated and become a pedagogic resource.
PMID- 29958351
TI - The management of diagnostic uncertainty and decision-making in genetics case
conferences.
AB - In this paper we examine one type of intraprofessional collaborative activity,
namely case conferences in a specialist genetics clinic. Our specific focus is on
how clinical geneticists manage decision-making through team talk in the event of
diagnostic uncertainty which is mainly attributable to limitations in the current
state of genomic knowledge, 'uncertain significances' associated with genetic
test results, and a lack of information/ evidence pertaining to cases under
discussion. The case conference then becomes a means to minimise the uncertainty
and arrive at decisions that optimise the significance of the results in terms of
clients' life trajectories. Adopting theme-oriented activity analysis, we examine
video-recorded data from five case conferences in Hong Kong. Beginning with a
prototypical structural mapping of the case conference activity type, our
analysis focuses on what we call 'uncertain cases'. Our findings highlight three
discourse types constitutive of team talk: pedagogic talk, diagnostic talk and
decisional talk. In paying particular attention to how uncertainty is formulated
and negotiated, we suggest that access to and assessment of different kinds of
evidence as well as the activity-specific expert role-positions of the
participants are crucial with regard to establishing a correct diagnosis and/or
striving towards a minimisation of current uncertainties.
PMID- 29958352
TI - Discourse types and (re)distribution of responsibility in simulated emergency
team encounters.
AB - Successful teamwork, constitutive of team talk, depends largely on shared
responsibility in the coordination of tasks in a goal-oriented way. This paper
examines how specific modes of talk or 'discourse types' are utilised by a
healthcare team in simulated emergency care. The data corpus comprises six video
recorded simulation training sessions in an emergency department at a large
Norwegian hospital. Our analysis focuses on the critical moment when the original
healthcare team is joined by other specialists in an ad hoc manner, which
necessitates the (re)distribution of expert responsibility in the management of
the patient's condition. We examine the interactional trajectories and, in
particular, the discourse types surrounding the critical moment which marks the
incorporation of the new team members. The analysis centres on three discourse
types (online commentary, offline commentary and metacommentary) that are
utilised in accomplishing the multiple tasks in a collaborative and coordinated
fashion. We suggest that team talk overlays and overlaps with distributed medical
work in highly charged decision-making contexts such as emergency care. The
findings have relevance for how healthcare professionals and students are trained
in multidisciplinary team talk and teamwork.
PMID- 29958353
TI - Editorial: Team work and team talk as distributed and coordinated action in
healthcare delivery.
AB - This special issue of Communication & Medicine is dedicated to the theme of
teamwork and team talk in healthcare delivery.
PMID- 29958354
TI - Conversation analysis and talk-extrinsic data in research on speech and language
therapy.
AB - The present article addresses the issue of combining conversation analysis (CA)
with talk-extrinsic data, with a specific focus on speech and language therapy
and education. Even though the use of CA together with other data sources is now
generally accepted, particularly in the field of 'applied CA', it is still
important to discuss how this is to be done, what pitfalls to avoid, and what
methodological problems might remain unresolved. The procedures from a Swedish
project on interaction in speech and language intervention that combines CA with
interviews and video-based retrospection sessions are used as a basis for
discussion. It is stressed that the fruitfulness of combining CA with talk
extrinsic data is strongly related to what research questions are asked, and what
values are ascribed to different empirical materials in relation to the overall
aims of a project. The article also addresses the potential risks of a
methodology such as CA when it is turned into 'just a tool' for detailed
transcription. Unless continuous attention is paid to CA's origin and its use for
applied purposes, it might become 'bleached', in the sense that it becomes solely
a technique, and its theoretical and methodological underpinnings get forgotten.
PMID- 29958355
TI - 'What should a woman do and imagine to have bulimia?': Co-constructing patient
expertise in psychotherapy with bulimia patients.
AB - One of the goals of psychotherapy with bulimia patients is identification of the
functions of the eating disorder in their lives. Thus, as in any
psychotherapeutic approach, the therapist should facilitate the patient's
disclosure of his or her experience of living with bulimia. Talking about one's
dysphoric experiences and, particularly in the case of bulimia, symptoms and
experiences that commonly deprive people with bulimia of dignity, constitutes an
emotional challenge for the patient and an equally challenging interactional task
for the therapist. Using the example of one therapy session with a female bulimia
patient, we examine how the therapist and the patient interactionally engage in
co-constructing the patient's expertise - involving epistemics of experience as
well as epistemics of expertise - concerning the illness in the interactional
here-and-now. Applying tools and insights from discourse and conversation
analysis, we examine the sequences in which the patient shifts the topical focus
from a general observation concerning bulimia to her personal experience, to be
further pursued interactionally by the therapist. We also discuss how the
therapist downgrades her epistemic position and (concurrently) foregrounds and
bolsters the patient's voice as expert to accomplish the session's therapeutic
goals.
PMID- 29958356
TI - Vulnerability of medical students and professionals to extreme work stress: A
select review of the literature.
AB - The goal of the paper is to describe the extent to which medical students and
professionals are vulnerable to extreme stress. A select review of existing
literature on this area has been undertaken, using the English-language online
databases EBSCO, Medline and PubMed. The search has identified 36 citations
relating to 6324 medical students and 28,285 medical staff (physicians,
residents, nurses). The review indicates that merely beginning medical studies is
a risk factor for stress, and that medical professionals, who are vulnerable to
extreme work stress, say that they do not receive enough support from their co
workers. They are also often notably impulsive, introverted, neurotic and
perfectionist, with low emotional intelligence and agreeableness, as well as low
and external locus of control. Additionally, from longitudinal studies we have
been able to identify psychological factors underpinning admission to a medical
university that may be useful for predicting future stress in medical career. The
results of this study may be taken into account when organizing psychological
intervention programs targeted at educating future medical professionals. It
seems that early identification of people at risk could reduce the impact of
stress related to medical career and enhance the somatic and mental health of
medical professionals.
PMID- 29958357
TI - Two models of ethical alignment through metacommunication in clinical situations.
AB - The literature on communication in patient-centred care typically focuses on
physicians' alignment strategies. The goals of these strategies are diagnostic
accuracy, effectiveness via compliance and patient-centredness. Although the
success of these strategies can to some extent be measured, the ethical standards
by which they are evaluated are not sufficiently clear. This article presents two
models of alignment through 'explicit' metacommunication, derived from two
different ethical perspectives on patient-centredness. The article first presents
the concept of metacommunication and identifies two ethical perspectives that
produce normative stands concerning patient-centredness: the logic of care and
internal morality. Second, the article presents two models of how
metacommunication can contribute to the visibility and accomplishment of these
two ethical perspectives in clinical alignment.
PMID- 29958358
TI - 'We are the barriers': Danish general practitioners' interpretations of why the
existential and spiritual dimensions are neglected in patient care.
AB - Although it is broadly recognized that health problems often involve existential
and spiritual dimensions, recent research shows that these aspects of illness are
rarely attended to by health professionals. Studies explain this in terms of
barriers to communication, but health professionals' firsthand experiences and
interpretations have so far been largely unexplored. Drawing on the theoretical
traditions of phenomenology and hermeneutics, the present study presents Danish
general practitioners' (GPs') experiences and interpretations of why the
existential and spiritual dimensions are marginalized in patient care. We
conducted seven focus groups, constituting a total sample of 31 GPs. Based on the
analytic strategy of Interpretative Phenomenological Analysis (IPA), our analysis
revealed that the GPs experienced and interpreted individual barriers as created
and fostered within dominant biomedical and secular cultures that are
characterized as 'solution focused' and 'faith frightened'. Many GPs further
understand themselves as barriers, because they are enculturated into these
dominating cultures. We discuss these findings through theoretical concepts such
as 'secondary socialization', 'system colonization' and 'secularization', and
suggest interventions that might challenge current practice culture.
PMID- 29958359
TI - Developing a new empathy-specific admissions test for applicants to medical
schools: A discourse-pragmatic approach.
AB - The ability to empathise with patients is an important professional skill for
doctors. Medical students practise this skill as part of their medical education,
and are tested on their use of empathy within their final examination. Evidence
shows that appropriate training makes a difference but that natural aptitude also
plays a role. Most medical schools, therefore, probe applicants' basic
understanding of empathy at admissions interviews. The purpose of the project
presented in this paper was to apply existing understanding of how empathy may be
communicated in a clinical context (building on a literature review by Pounds
[2011]) to develop a new empathy-specific medical admissions interview station,
probing applicants' empathic communicative performance (not just theoretical
knowledge) and fitting the widely used Multiple Mini Interview (MMI) format. The
paper outlines how this tool was developed, trialled and implemented by: (1)
conceptualising empathic communication in discourse-pragmatic terms - that is, as
a set of specific but context-dependant empathic speech acts; and (2) formulating
and trialling a written and two oral versions of a situational test, capable of
probing the applicants' ability to communicate empathically in everyday
conversation and suitable for use at Norwich Medical School and other similar
educational institutions.
PMID- 29958360
TI - Small talk as work talk: Enacting the patient-centered approach in nurse
practitioner-patient visits.
AB - Small talk in medical visits has received ample attention; however, small talk
that occurs at the close of a medical visit has not been explored. Small talk,
with its focus on relational work, is an important aspect of medical care,
particularly so considering the current focus in the US on the patient-centered
approach and the desire to construct positive provider- patient relationships,
which have been shown to contribute to higher patient satisfaction and better
health outcomes. Therefore, even small talk that is unrelated to the
transactional aspect of the medical visit in fact serves an important function.
In this article, I analyze small talk exchanges between nurse practitioners (NPs)
and their patients which occur after the transactional work of the visit is
completed. I focus on two exchanges which highlight different interactional
goals. I argue that these examples illustrate a willingness on the part of all
participants to extend the visit solely for the purpose of constructing positive
provider-patient relationships. Furthermore, because exchanges occur after the
'work' of the visit has been completed, they have the potential to construct
positive relationships that extend beyond the individual visit.
PMID- 29958361
TI - Comparing doctor-elderly patient communication between traditional Chinese
medicine and Western medicine encounters: Data from China.
AB - Effective doctor-patient communication has been widely endorsed as pivotal for
optimal medical care and the building of a positive and lasting relationship
between caregivers and patients. While the literature suggests that traditional
Chinese medicine (TCM) doctors have better interpersonal skills than Western
medicine (WM) doctors, and that the doctor-patient relationship in TCM is more
lasting, a comparison of specific communication behaviors in both encounters has
not yet been carried out. This paper examines the similarities and differences in
communication behaviors between these two types of consultations in relation to
doctor-elderly patient communication. Forty-five consultations were included for
analysis using the Roter Interaction Analysis System (RIAS). Significant
differences were found in communication behaviors at the level of lifestyle and
psychosocial exchanges, type of questions, non-medical small talk, and emotional
disclosure. The study's limitations and implications are discussed.
PMID- 29958362
TI - Opportunities and challenges of entertainment-education: Learning about
Parkinson's disease via The Michael J. Fox Show.
AB - Health topics are omnipresent in the media. However, although both informational
and entertainment formats can increase public understanding of health and
illness, media representations of diseases involve challenges as well as
opportunities. The entertainment-education (E-E) approach highlights the positive
effects of incorporating health messages into entertainment media. The goal of
influencing awareness, knowledge and attitudes is reached by transporting the
audience into a narrative, which as such enhances persuasive effects and
suppresses counterarguing. The NBC sitcom The Michael J. Fox Show (TMJFS) is an E
E format inspired by the actor's own experiences with Parkinson's disease (PD).
Using TMJFS as an exemplar, we conducted a multimethodological study to
understand both the challenges and the opportunities of E-E comedy formats. A
content analysis focusing on the representation of PD in TMJFS showed a focus on
motoric symptoms of PD. Subsequent recap analyses and qualitative interviews were
conducted to better understand different readings of the show in terms of its
informative and entertaining aspects. Additionally, we performed a standardized
online survey and an experiment to measure attitudinal effects of TMJFS.
PMID- 29958363
TI - Doctors' and interpreters' conversational styles in paediatric diabetes
encounters: A case study of empowering language use.
AB - During the last few decades, ideas of empowerment, person centered care (PCC) and
shared decision-making (SDM) have informed western health care. An increasing
interest in conversational styles aligned with these ideas is visible e.g. in the
work to make motivational interviewing (MI) an evidence based communicative
practice. But linguistic competence is needed to identify the subtle nuances of
the communicative practices in a doctor-patient consultation. It is therefore
particularly important to investigate conversation styles in mediated encounters
with immigrant patients. Mitigation strategies (indirect speech, hedging etc.)
and confirming strategies (back-channelling, encouragement etc.) are considered
to be typical of an 'empowering' conversation style. The distribution of these
features in encounters with or without interpreters was analysed in a case study
of two consultations with the same doctor in a children's diabetes clinic in
Sweden. The results of this study indicate that the mitigation strategies and
confirming strategies characteristic of a conversation style aimed at
strengthening and encouraging the patient tend to get lost in mediation. The
implications of these findings are discussed.
PMID- 29958364
TI - 'Let's talk more about this': An analysis of how experts engage novice physicians
in pedagogical dialogue.
AB - This exploratory study examines conversations between faculty physician
preceptors and resident physicians to identify communicative actions that
encourage pedagogical dialogue. Using a modified grounded theory approach, this
study considers resident-preceptor conversations at the levels of the
conversational exchange and the clause. Four categories of exchanges emerged from
the analysis: presenting the case, teaching clinical concepts, initiating
clinical discussion, and offering/requesting direct instruction. Focusing on the
latter two categories, this study identifies common communicative actions in the
clauses of speakers' conversational turns. I contend that clinical-discussion
exchanges best support the academic goal of these conversations by engaging
novices with open-ended, interpretation-focused questions, proposals, and
assessments; in contrast, direct-instruction exchanges support the workplace
objective of treating patients through imperative proposals and procedure-focused
questions and assessments. This analysis offers communication scholars insight
into how expert-novice conversations support professionalization and provides
preceptors with an understanding of communicative actions that may facilitate
pedagogical dialogue.
PMID- 29958365
TI - Exploring the meaning of living with HIV as a chronic illness in Kenya: A
narrative inquiry.
AB - Since the introduction of antiretroviral medications, HIV has been regarded as a
chronic illness. However, people living with HIV continue to experience social
consequences of HIV infection such as stigma, discrimination, violence, and other
human rights violations. In this paper, we focus on the experiences of Atoti, a
person living with HIV in Kenya. We argue that HIV remains a biographically
disruptive and exceptional illness that is complicated by its invisibility and
unpredictable trajectory. Based on Atoti's experiences, we argue that Bury's
(1982) concept of biographical disruption, used to explain the social processes
of a person suffering a chronic illness, does not fully capture the complexity of
experiencing living with HIV. Focusing on life as a whole, rather than on the
disease response and process as a biographical disruption, allows for a deeper
appreciation of HIV's complexity as a medical illness with major social
ramifications.
PMID- 29958366
TI - Verbal compliance-gaining strategies used by male physicians and patient
healthcare experience.
AB - This study explores male physicians' use of verbal compliance gaining strategies
to encourage patients to adhere to medication regimens, lifestyle changes, or
future appointments, and assesses which strategies are associated with patients'
reported healthcare experiences. Five physicians from a family practice clinic in
northern British Columbia, Canada, were audio-recorded while interacting with 31
patients during actual consultations. Compliance-gaining utterances were coded
into five categories of strategies, while patient experience with care was
assessed using a questionnaire. A number of intriguing findings emerged: direct
orders were related to a more negative experience with interpersonal aspects of
care, but were fairly frequently used, especially with female patients.
Persuasion was the only strategy that promoted a positive patient experience, but
was rarely used. However, the effect of persuasion on patient experience was no
longer significant when adjusting for patients' health status. Physicians relied
mostly on motivation strategies to encourage adherence, but these strategies were
not related to patients' assessment of their healthcare experiences. These
results suggest that the most frequently used verbal compliance gaining
strategies by physicians are not always appreciated by patients. To be more
effective, it is necessary to inform physicians about which compliance-gaining
strategies promote a positive patient healthcare experience.
PMID- 29958367
TI - Patients' practices for taking the initiative in decision-making in outpatient
psychiatric consultations.
AB - In spite of increasing advocacy for patients' participation in psychiatric
decision-making, there has been little research on how patients actually
participate in decision-making in psychiatric consultations. This study explores
how patients take the initiative in decision-making over treatment in outpatient
psychiatric consultations in Japan. Using the methodology of conversation
analysis, we analyze 85 video-recorded ongoing consultations and find that
patients select between two practices for taking the initiative in decision
making: making explicit requests for a treatment and displaying interest in a
treatment without explicitly requesting it. A close inspection of transcribed
interaction reveals that patients make explicit requests under the circumstances
where they believe the candidate treatment is appropriate for their condition,
whereas they merely display interest in a treatment when they are not certain
about its appropriateness. By fitting practices to take the initiative in
decision-making with the way they describe their current condition, patients are
optimally managing their desire for particular treatments and the validity of
their initiative actions. In conclusion, we argue that the orderly use of the two
practices is one important resource for patients' participation in treatment
decision-making.
PMID- 29958368
TI - Letter to the Editor Regarding "Natalizumab-Associated Primary Central Nervous
System Lymphoma".
PMID- 29958369
TI - Cranial Osteomyelitis: The Old Enemy Is Back.
PMID- 29958370
TI - Timing of Early Cranioplasty for Traumatic Brain Injury-the Debate Goes On.
PMID- 29958371
TI - Size of Therapeutic Decompressive Craniectomy.
PMID- 29958372
TI - Neuroscientific Perspective on Genuineness of a Smile.
PMID- 29958373
TI - Hyponatremia Following Aneurysmal Subarachnoid Hemorrhage.
PMID- 29958374
TI - In Reply to "Hyponatremia Following Aneurysmal Subarachnoid Hemorrhage".
PMID- 29958375
TI - "Wounded Meningioma Syndrome": Postoperative Exacerbation of Brain Edema in Brain
Invasive Meningioma.
PMID- 29958376
TI - In Reply to ""Wounded Meningioma Syndrome": Postoperative Exacerbation of Brain
Edema in Brain-Invasive Meningioma".
PMID- 29958377
TI - Streptococcus mutans with Collagen-Binding Protein: From Oral Cavity to Brain.
PMID- 29958378
TI - In Reply to "Streptococcus mutans with Collagen-Binding Protein: From Oral Cavity
to Brain".
PMID- 29958379
TI - Letter to the Editor Regarding "Endovascular Mechanical Thrombectomy for Acute
Ischemic Stroke Under General Anesthesia Versus Conscious Sedation: A Systematic
Review and Meta-Analysis".
PMID- 29958380
TI - In Reply to the Letter to the Editor Regarding "Endovascular Mechanical
Thrombectomy for Acute Ischemic Stroke Under General Anesthesia Versus Conscious
Sedation: A Systematic Review and Meta-Analysis".
PMID- 29958382
TI - Psychosocial Correlates of Food Addiction and Its Association with Quality of
Life in a Non-Clinical Adolescent Sample.
AB - BACKGROUND: Most studies related to food addiction have focused on assessing food
addiction among adult populations. However, evidence in adolescents has been
limited. The aim of this study was to investigate the prevalence of food
addiction in a non-clinical adolescent sample. Psychosocial correlations of food
addiction and associations with different quality of life dimensions were also
tested. METHODS: The sample included 593 Chinese adolescents (51.9% female; age
range: 13-17 years). All participants provided sociodemographic information and
completed questionnaires regarding food addiction, depression, self-esteem,
loneliness, psychosocial problems, and quality of life (QoL). RESULTS: The
prevalence of food addiction was 6.91% in our sample. A multivariable logistic
regression indicated that food addiction was associated with depression (AOR =
2.58; 95% CI: 1.32-5.05), low self-esteem (AOR = 2.75; 95% CI: 1.31-5.78), and
loneliness (AOR = 2.30; 95% CI: 1.14-4.65). After multivariable adjustments for
sociodemographic and psychological variables, food addiction was associated with
lower overall QoL and psychosocial health of QoL. CONCLUSIONS: Food addiction may
be common among Chinese adolescents. Food addiction was associated with
depression, low self-esteem, and loneliness. Lastly, food addiction was also
associated with lower overall QoL and psychosocial health of QoL. Future public
health programs and interventions consider targeting the factors associated with
food addiction to increase healthy eating behaviors among adolescents.
PMID- 29958383
TI - Role of Inosine-Uracil Base Pairs in the Canonical RNA Duplexes.
AB - Adenosine to inosine (A-I) editing is the most common modification of double
stranded RNA (dsRNA). This change is mediated by adenosine deaminases acting on
RNA (ADARs) enzymes with a preference of U>A>C>G for 5′ neighbor and
G>C=A>U or G>C>U=A for 3′ neighbor. A-I editing occurs most frequently in
the non-coding regions containing repetitive elements such as ALUs. It leads to
disruption of RNA duplex structure, which prevents induction of innate immune
response. We employed standard and biased molecular dynamics (MD) simulations to
analyze the behavior of RNA duplexes with single and tandem inosine-uracil (I-U)
base pairs in different sequence context. Our analysis showed that the I-U pairs
induce changes in base pair and base pair step parameters and have different
dynamics when compared with standard canonical base pairs. In particular, the
first I-U pair from tandem I-U/I-U systems exhibited increased dynamics depending
on its neighboring 5′ base. We discovered that UII sequence, which is
frequently edited, has lower flexibility compared with other sequences (AII, GII,
CII), hence it only modestly disrupts dsRNA. This might indicate that the UAA
motifs in ALUs do not have to be sufficiently effective in preventing immune
signaling.
PMID- 29958384
TI - Socio-Cultural and Environmental Factors that Influence Weight-Related Behaviors:
Focus Group Results from African-American Girls and Their Mothers.
AB - African-American girls experience higher rates of obesity than other youth and
are more likely to live in environments that may inhibit healthy lifestyles.
Focus groups with African-American girls (14.2 +/- 2.36 years) and their mothers
were conducted to explore socio-cultural and physical factors within the home,
neighborhood, and school environments that influence physical activity (PA) and
food choices (i.e., availability and accessibility). Being active at home was
dependent on availability of unstructured PA, possibility of activity with
family/friends/pet, structured sports in the community, and perceived safety of
neighborhood. Girls reported unhealthy foods and excessive snacking as issues at
home while citing choice of school meals vs. vending machine items and easy
accessibility to fast food restaurants as concerns at school. Learning more about
the PA and food environments is a fundamental step to develop effective and
innovative, environmental strategies to address unhealthy weight-related
behaviors in this population.
PMID- 29958385
TI - Eating Healthy, Growing Healthy: Impact of a Multi-Strategy Nutrition Education
on the Assortments of Beverages Served in Preschools, Poland.
AB - Day-care centers are the ideal place for conducting nutrition intervention to
improve children’s nutrition. The aim of this study is to evaluate the
effectiveness of a multi-strategy childcare-base intervention in improving
compliance with nutrition guidelines regarding beverages supply in preschools.
The intervention included the staff training, audit, feedback, and ongoing
support provided by trained educators. The emphasis was put on adequate
nutrition, including recommended beverages, reducing sugar-sweetened beverages
and increasing water availability. Enrolled were 478 full-board preschools from
Poland (4.2% of all preschools in the country). The assortment of beverages
served to children within ten consecutive days was assessed based on menus and
inventory reports at the baseline, and three months after the intervention.
Education increased significantly the percentage of preschools serving water to
meals and between meals (67% vs. 83% and 93% vs. 99%, respectively), fruit/herbal
tea (75% vs. 81%), and natural fruit juices (46% vs. 56%). The percentage of
preschools offering fruit/soft drinks decreased from 23% to 15%. This study shows
that education has a great potential in improving the assortment of beverages
served in preschools. Future research is needed to determine barriers in better
optimizing the assortment of beverages in preschool settings.
PMID- 29958386
TI - Physical Activity and Outdoor Play of Children in Public Playgrounds-Do Gender
and Social Environment Matter?
AB - BACKGROUND: Few studies have delved into the relationship of the social
environment with children’s physical activity and outdoor play in public
playgrounds by considering gender differences. The aim of the present study was
to examine gender differences and the relationship of the social environment with
children’s physical activity and outdoor play in public playgrounds.
METHODS: A quantitative, observational study was conducted at ten playgrounds in
one district of a middle-sized town in Germany. The social environment, physical
activity levels, and outdoor play were measured using a modified version of the
System for Observing Play and Leisure Activity in Youth. RESULTS: In total, 266
observations of children (117 girls/149 boys) between four and 12 years old were
used in this analysis. Significant gender differences were found in relation to
activity types, but not in moderate-to-vigorous physical activity (MVPA). The
presence of active children was the main explanatory variable for MVPA. In the
models stratified by gender, the presence of opposite-sex children was a
significant negative predictor of MVPA in girls but not in boys. CONCLUSIONS: The
presence of active children contributes to children’s physical activity
levels in public playgrounds. Girls’ physical activity seems to be
suppressed in the presence of boys.
PMID- 29958387
TI - Weighted Gene Co-Expression Network Analysis Reveals Dysregulation of
Mitochondrial Oxidative Phosphorylation in Eating Disorders.
AB - The underlying mechanisms of eating disorders (EDs) are very complicated and
still poorly understood. The pathogenesis of EDs may involve the interplay of
multiple genes. To investigate the dysregulated gene pathways in EDs we analyzed
gene expression profiling in dorsolateral prefrontal cortex (DLPFC) tissues from
15 EDs cases, including 3 with anorexia nervosa (AN), 7 with bulimia nervosa
(BN), 2 AN-BN cases, 3 cases of EDs not otherwise specified, and 102 controls. We
further used a weighted gene co-expression network analysis to construct a gene
co-expression network and to detect functional modules of highly correlated
genes. The functional enrichment analysis of genes in co-expression modules
indicated that an altered mitochondrial oxidative phosphorylation process may be
involved in the pathogenesis of EDs.
PMID- 29958388
TI - Flower-like Cu2SnS3 Nanostructure Materials with High Crystallinity for Sodium
Storage.
AB - In this study, ternary Cu2SnS3 (CTS) nanostructure materials with high
crystallinity were successfully prepared via a facile solvothermal method, which
was followed by high-temperature treatment. The morphology of the as-synthesized
samples is uniform flower-like spheres, with these spheres consisting of
hierarchical nanosheets and possessing network features. Sodium storage
measurements demonstrate that the annealed CTS electrodes have high initial
reversible capacity (447.7 mAh·g−1 at a current density of 100
mA·g−1), good capacity retention (200.6 mAh·g−1 after
50 cycles at a current density of 100 mA·g−1) and considerable rate
capability because of their high crystallinity and unique morphology. Such good
performances indicate that the high crystallinity CTS is a promising anode
material for sodium ion batteries.
PMID- 29958389
TI - Raloxifene/SBE-beta-CD Inclusion Complexes Formulated into Nanoparticles with
Chitosan to Overcome the Absorption Barrier for Bioavailability Enhancement.
AB - Raloxifene (RXF) is a hormone-like medication used for treating postmenopausal
osteoporosis and estrogen-dependent breast cancer, yet associated with bad low
bioavailability due to poor solubility. This study was intended to develop
cyclodextrin/chitosan nanoparticles (ccNPs) for oral delivery of RXF in order to
enhance the oral bioavailability. RXF-loaded ccNPs (RXF-ccNPs) were prepared by
cyclodextrin inclusion followed by complexation with chitosan. RXF-ccNPs were
fully characterized by particle size, morphology and in vitro drug release. The
oral delivery efficacy and transepithelial transport potential were evaluated by
pharmacokinetics, in situ single-pass intestinal perfusion, cellular uptake and
ex vivo imaging. The resulting RXF-ccNPs were around 165 nm in particle size with
a narrow distribution. The oral bioavailability of RXF was enhanced by 2.6 folds
through ccNPs compared to RXF suspensions in rats. It was shown that RXF-ccNPs
could improve the intestinal permeability of RXF, increase the cellular uptake of
RXF and facilitate its transport across the absorptive epithelia. The results
indicate that our developed ccNPs based on sulfobutylether-β-cyclodextrin
and oligochitosan are a promising vehicle to orally deliver poorly water-soluble
drugs over and above RXF.
PMID- 29958390
TI - Cultural Features Influencing Eating, Overweight, and Obesity in the Roma People
of South Bohemia.
AB - : This article describes the important cultural specifics that impact on
treatment of overweight and obesity for the Roma people of South Bohemia.
METHODS: Data on health and nutrition were collected using a semi-structured
interview of 302 Roma adults (quantitative phase). A further 25 participants
received in-depth interviews regarding their eating and lifestyle habits and
perceptions about obesity and overweight (qualitative phase). Height and weight
were measured with calibrated scales and stadiometer. Qualitative data were
analyzed with the “grounded theory” method. RESULTS: The participants
reported a relatively high consumption of high-sugar drinks and foods compared to
fruits and vegetables. Lifestyle factors increasing risk of overweight identified
from the qualitative interview included unemployment, socially isolating housing,
poor transport, poverty, inactivity, tobacco smoking, and for women weight gain
after childbirth. Also identified was the need for better health literacy.
CONCLUSIONS: Effective health education may help to address risk factors for
overweight and obesity in Roma peoples. Other measures include improved
socioeconomic status and housing security, and improved health literacy of the
Roma people.
PMID- 29958391
TI - Methods of Isolation, Characterization and Expansion of Human Adipose-Derived
Stem Cells (ASCs): An Overview.
AB - Considering the increasing interest in adipose-derived stem cells (ASCs) in
regenerative medicine, optimization of methods aimed at isolation,
characterization, expansion and evaluation of differentiation potential is
critical to ensure (a) the quality of stem cells also in terms of genetic
stability; (b) the reproducibility of beneficial effects; and (c) the safety of
their use. Numerous studies have been conducted to understand the mechanisms that
regulate ASC proliferation, growth and differentiation, however standard
protocols about harvesting and processing techniques are not yet defined. It is
also important to note that some steps in the procedures of harvesting and/or
processing have been reported to affect recovery and/or the physiology of ASCs.
Even considering the great opportunity that the ASCs provide for the
identification of novel molecular targets for new or old drugs, the definition of
homogeneous preparation methods that ensure adequate quality assurance and
control, in accordance with current GMPs (good manufacturing practices), is
required. Here, we summarize the literature reports to provide a detailed
overview of the methodological issues underlying human ASCs isolation,
processing, characterization, expansion, differentiation techniques, recalling at
the same time their basilar principles, advantages and limits, in particular
focusing on how these procedures could affect the ASC quality, functionality and
plasticity.
PMID- 29958392
TI - Toxicity of Ochratoxin to Early Life Stages of Zebrafish (Danio rerio).
AB - Ochratoxin A (OTA) is a known contaminant in fish feed but its effect on fish
health remains rather unknown. A study was conducted to investigate the effects
of different concentrations of ochratoxin on early life stages of zebrafish
(Danio rerio). The tests with ochratoxin A showed a correlation between the
exposure to mycotoxin and the amount of damage. The mortality rate and the
incidents of embryonal damage was increased by increasing ochratoxin
concentrations. The calculations resulted in a lethal concentration for 50% of
the embryos (LC50) of 0.29 mg/L and a concentration at which 50% of the animals
showed impairment (EC50) of 0.36 mg/L after 96 h of exposure. During the test,
reduced heart rates were also observed revealing a clear dose-response
relationship. The EC50 determination for this endpoint was 1.26 mg/L after 72 h
of exposure. The measurement of oxidative stress was proven to be the most
sensitive system to indicate OTA effects on the zebrafish embryos with an EC50
value of 0.067 mg/L after 72 h of exposure. The test validity was given because
the control test with 3,4-Dichloroaniline (3,4-D) showed a LC50 value of 2.88 mg
after 96 h of exposure which is comparable to the available reference values.
According to the current knowledge, these experimental doses did not exceed the
environmental concentrations of this ochratoxin A. However, this study raises
concerns about the effects of ochratoxin on fish.
PMID- 29958393
TI - The Impact of Maternal Diet during Pregnancy and Lactation on the Fatty Acid
Composition of Erythrocytes and Breast Milk of Chilean Women.
AB - Maternal diet during pregnancy is relevant for fatty acid supply during fetal
life and lactation. Arachidonic (AA) and docosahexaenoic (DHA) acids are also
relevant for the normal growth and development of brain and visual system. AA and
DHA provided by the mother to the fetus and infant are directly associated with
maternal dietary intake and body stores. Our aim was to evaluate the impact of
maternal diet, specially referring to the quality of fatty acid intake, in a
sample of Chilean women during last stage of pregnancy and across the lactation
period. Fifty healthy pregnant women (age range 20-33 years) were studied from
the 6th month of pregnancy and followed until 6th month of lactation period. Diet
characteristics were evaluated through food frequency questionnaires. Fatty acids
composition of erythrocyte phospholipids and breast milk samples was assessed by
gas-liquid chromatography. Overall, women had high saturated fatty acids intake
with sufficient intake of mono- and polyunsaturated fatty acids (PUFA). Diet was
high in n-6 PUFA and low in n-3 PUFA (mainly DHA), with imbalanced n-6/n-3 PUFA
ratio. Erythrocytes and breast milk DHA concentration was significantly reduced
during lactation compared to pregnancy, a pattern not observed for AA. We
concluded that is necessary to increase the intake of n-3 PUFA during pregnancy
and lactation by improving the quality of consumed foods with particular emphasis
on its DHA content.
PMID- 29958394
TI - Unexpected Event Prediction in Wire Electrical Discharge Machining Using Deep
Learning Techniques.
AB - Theoretical models of manufacturing processes provide a valuable insight into
physical phenomena but their application to practical industrial situations is
sometimes difficult. In the context of Industry 4.0, artificial intelligence
techniques can provide efficient solutions to actual manufacturing problems when
big data are available. Within the field of artificial intelligence, the use of
deep learning is growing exponentially in solving many problems related to
information and communication technologies (ICTs) but it still remains scarce or
even rare in the field of manufacturing. In this work, deep learning is used to
efficiently predict unexpected events in wire electrical discharge machining
(WEDM), an advanced machining process largely used for aerospace components. The
occurrence of an unexpected event, namely the change of thickness of the machined
part, can be effectively predicted by recognizing hidden patterns from process
signals. Based on WEDM experiments, different deep learning architectures were
tested. By using a combination of a convolutional layer with gated recurrent
units, thickness variation in the machined component could be predicted in 97.4%
of cases, at least 2 mm in advance, which is extremely fast, acting before the
process has degraded. New possibilities of deep learning for high-performance
machine tools must be examined in the near future.
PMID- 29958395
TI - Defining the Optimal Dietary Approach for Safe, Effective and Sustainable Weight
Loss in Overweight and Obese Adults.
AB - Various dietary approaches with different caloric content and macronutrient
composition have been recommended to treat obesity in adults. Although their
safety and efficacy profile has been assessed in numerous randomized clinical
trials, reviews and meta-analyses, the characteristics of the optimal dietary
weight loss strategy remain controversial. This mini-review will provide general
principles and practical recommendations for the dietary management of obesity
and will further explore the components of the optimal dietary intervention. To
this end, various dietary plans are critically discussed, including low-fat
diets, low-carbohydrate diets, high-protein diets, very low-calorie diets with
meal replacements, Mediterranean diet, and diets with intermittent energy
restriction. As a general principle, the optimal diet to treat obesity should be
safe, efficacious, healthy and nutritionally adequate, culturally acceptable and
economically affordable, and should ensure long-term compliance and maintenance
of weight loss. Setting realistic goals for weight loss and pursuing a balanced
dietary plan tailored to individual needs, preferences, and medical conditions,
are the key principles to facilitate weight loss in obese patients and most
importantly reduce their overall cardiometabolic risk and other obesity-related
comorbidities.
PMID- 29958396
TI - Morphological Characteristics, Nutrients, and Bioactive Compounds of Zizania
latifolia, and Health Benefits of Its Seeds.
AB - Zizania latifolia (tribe Oryzeae Dum., subfamily Oryzoideae Care, family
Gramineae) is native to East Asian countries. The seeds of Z. latifolia (Chinese
wild rice) have been consumed as a cereal in China for >3000 years. Z. latifolia
forms swollen culms when infected with Ustilago esculenta, which is the second
most-cultivated aquatic vegetable in China. The current review summarizes the
nutrients and bioactive compounds of Z. latifolia, and health benefits of its
seeds. The seeds of Z. latifolia contain proteins, minerals, vitamins, and
bioactive compounds, the activities of which—for example, antioxidant
activity—have been characterized. Various health benefits are associated
with their consumption, such as alleviation of insulin resistance and
lipotoxicity, and protection against cardiovascular disease. Chinese wild rice
may be used to prevent and treat metabolic disease, such as diabetes, obesity,
and cardiovascular diseases. Various compounds were isolated from the swollen
culm, and aerial parts of Z. latifolia. The former suppresses osteoclast
formation, inhibits growth of rat glioma cells, and may act as antioxidants and
immunomodulators in drugs or foods. The latter exerts anti-fatigue, anti
inflammatory, and anti-allergic effects. Thus, Z. latifolia may be used to
produce nutraceuticals and functional foods.
PMID- 29958397
TI - Intake of Baked Cod Fillet Resulted in Lower Serum Cholesterol and Higher Long
Chain n-3 PUFA Concentrations in Serum and Tissues in Hypercholesterolemic Obese
Zucker fa/fa Rats.
AB - Increasing evidence indicates that lean fish consumption may benefit
cardiovascular health. High cholesterol and low n-3 PUFA concentrations in serum
are associated with an increased risk of coronary heart disease; therefore, it is
of interest to investigate effects of cod intake on cholesterol and n-3 PUFAs in
serum and tissues. Hypercholesterolemic obese Zucker fa/fa rats were fed diets
containing 25% protein from baked cod fillet and 75% protein from casein (Baked
Cod Diet), or casein as the sole protein source (Control Diet) for four weeks.
Consuming Baked Cod Diet resulted in lower serum cholesterol and lower hepatic
mRNA concentrations of HMG-CoA reductase and sterol O-acyltransferase-2 without
affecting serum bile acid concentration, faecal excretion of cholesterol and bile
acid, and hepatic concentrations of bile acids, cholesterol and cholesterol 7
alpha-hydroxylase mRNA when compared to Control Diet. Rats fed Baked Cod Diet had
higher concentrations of n-3 PUFAs in serum, liver, skeletal muscle and adipose
tissue. To conclude, baked cod fillet intake resulted in lower serum cholesterol,
which was probably caused by lower endogenous cholesterol synthesis, and higher n
3 PUFA in serum and tissues in obese Zucker fa/fa rats. These findings support
the evidence that lean fish consumption might benefit cardiovascular health.
PMID- 29958398
TI - An Overview of Current Pretreatment Methods Used to Improve Lipid Extraction from
Oleaginous Micro-Organisms.
AB - Microbial oils, obtained from oleaginous microorganisms are an emerging source of
commercially valuable chemicals ranging from pharmaceuticals to the petroleum
industry. In petroleum biorefineries, the microbial biomass has become a
sustainable source of renewable biofuels. Biodiesel is mainly produced from oils
obtained from oleaginous microorganisms involving various upstream and downstream
processes, such as cultivation, harvesting, lipid extraction, and
transesterification. Among them, lipid extraction is a crucial step for the
process and it represents an important bottleneck for the commercial scale
production of biodiesel. Lipids are synthesized in the cellular compartment of
oleaginous microorganisms in the form of lipid droplets, so it is necessary to
disrupt the cells prior to lipid extraction in order to improve the extraction
yields. Various mechanical, chemical and physicochemical pretreatment methods are
employed to disintegrate the cellular membrane of oleaginous microorganisms. The
objective of the present review article is to evaluate the various pretreatment
methods for efficient lipid extraction from the oleaginous cellular biomass
available to date, as well as to discuss their advantages and disadvantages,
including their effect on the lipid yield. The discussed mechanical pretreatment
methods are oil expeller, bead milling, ultrasonication, microwave, high-speed
and high-pressure homogenizer, laser, autoclaving, pulsed electric field, and non
mechanical methods, such as enzymatic treatment, including various emerging cell
disruption techniques.
PMID- 29958399
TI - Interference of Quercetin on Astragalus Polysaccharide-Induced Macrophage
Activation.
AB - Polysaccharides, which exert immunoregulatory effects, are becoming more and more
popular as food supplements; however, certain components of ordinary foods could
be reducing the polysaccharides beneficial effects. Quercetin, a flavonoid found
in common fruits and vegetables, is one such component. This study investigated
the effects of quercetin on Astragalus polysaccharide RAP induced-macrophage
activation. The results show quercetin decreases the NO production and iNOS gene
expression in RAW264.7 cells, and it inhibits the production of cytokines in
RAW264.7 cells and peritoneal macrophages. Western blot analysis results suggest
that quercetin inhibits the phosphorylation of Akt/mTORC1, MAPKs, and TBK1, but
has no effect on NF-κB in RAP-induced RAW264.7 cells. Taken together, the
results show that quercetin partly inhibits macrophage activation by the
Astragalus polysaccharide RAP. This study demonstrates that quercetin-containing
foods may interfere with the immune-enhancing effects of Astragalus
polysaccharide RAP to a certain extent.
PMID- 29958400
TI - Prognostic Value of Iron-Homeostasis Regulating Peptide Hepcidin in Coronary
Heart Disease-Evidence from the Large AtheroGene Study.
AB - Iron is essential in terms of oxygen utilization and mitochondrial function. The
liver-derived peptide hepcidin has been recognized as a key regulator of iron
homeostasis. Since iron metabolism is crucially linked to cardiovascular health,
and low hepcidin was proposed as potential new marker of iron metabolism, we
aimed to evaluate the prognostic value of hepcidin in a large cohort of patients
with coronary heart disease (CHD). Serum levels of hepcidin were determined at
baseline in patients with angiographically documented CHD. The main outcome
measure was non-fatal myocardial infarction (MI) or cardiovascular death. During
a median follow-up of 4.1 years, 10.3% experienced an endpoint. In Cox regression
analyses for hepcidin the hazard ratio for future cardiovascular death or MI was
1.03 (95% confidence interval (CI) 0.91-1.18, p = 0.63) after adjustment for sex
and age. This association virtually did not change after additional adjustment
for body mass index (BMI), smoking status, hypertension, diabetes, dyslipidemia,
and surrogates of cardiac function (NT-proBNP), size of myocardial necrosis
(troponin I), and anemia (hemoglobin). In this study, by far the largest
evaluating the predictive value of hepcidin, hepcidin levels were not associated
with future MI or cardiovascular death. This implicates a limited, if any, role
for hepcidin in secondary cardiovascular risk prediction.
PMID- 29958401
TI - Thickness Characterization Toolbox for Transparent Protective Coatings on Polymer
Substrates.
AB - The thickness characterization of transparent protective coatings on functional,
transparent materials is often problematic. In this paper, a toolbox to determine
the thicknesses of a transparent coating on functional window films is presented.
The toolbox consists of a combination of secondary ion mass spectrometry and
profilometry and can be transferred to other transparent polymeric materials. A
coating was deposited on designed model samples, which were characterized with
cross-sectional views in transmission and in scanning/transmission electron
microscopy and ellipsometry. The toolbox was then used to assess the thicknesses
of the protective coatings on the pilot-scale window films. This coating was
synthesized using straightforward sol-gel alkoxide chemistry. The kinetics of the
condensation are studied in order to obtain a precursor that allows fast drying
and complete condensation after simple heat treatment. The shelf life of this
precursor solution was investigated in order to verify its accordance to
industrial requirements. Deposition was performed successfully at low
temperatures below 100 °C, which makes deposition on polymeric foils
possible. By using roll-to-roll coating, the findings of this paper are easily
transferrable to industrial scale. The coating was tested for scratch resistance
and adhesion. Values for the emissivity (ε) of the films were recorded to
justify the use of the films obtained as infrared reflective window films. In
this work, it is shown that the toolbox measures similar thicknesses to those
measured by electron microscopy and can be used to set a required thickness for
protective coatings.
PMID- 29958402
TI - Seaweed Extract (Stella Maris(r)) Activates Innate Immune Responses in
Arabidopsis thaliana and Protects Host against Bacterial Pathogens.
AB - Insects and pathogenic infections (bacteria, viruses and fungi) cause huge losses
in agriculturally important crops yearly. Due to the rise in pesticide and
antibiotic resistance, our crops and livestock are increasingly at risk. There is
a rising demand for environmentally friendly solutions to prevent crop decreases.
Components of Ascophyllum nodosum seaweed extracts were recently found to boost
plant immunity. The stimulatory activities of the A.nodosum marine alga-derived
extract (Stella Maris®) were investigated in a broad range of immune assays.
Elevated hydrogen peroxide production measured in a chemiluminescence assay
suggested that the extract elicited a strong burst of reactive oxygen species.
Arabidopsis seedlings treated with Stella Maris® activated the expression of
WRKY30, CYP71A12 and PR-1 genes, the induction of which represent early, mid and
late plant immune response, respectively. Finally, this study found that Stella
Maris® inhibited the growth of multiple bacterial pathogens, including an
opportunistic human pathogen that has demonstrated pathogenicity in plants. In
summary, the pre-treatment with the seaweed extract protected Arabidopsis against
subsequent infection by these pathogens.
PMID- 29958403
TI - Influence of Diet and Gender on Plasma DPP4 Activity and GLP-1 in Patients with
Metabolic Syndrome: An Experimental Pilot Study.
AB - BACKGROUND: Glucagon-Like Peptide-1 (GLP-1) is hydrolyzed by Dipeptidyl-Peptidase
4 (DPP4), and several studies suggest that both GLP-1 and DPP4 inhibitors have
potentially beneficial effects on cardiovascular risks. The objective of this
study was to analyze the differences between plasma GLP-1 and DPP4 activity in
male and female patients with metabolic syndrome, and its relationship with
physiological and metabolic parameters. The study included 25 apparently healthy
Controls (C) and 21 Metabolic Syndrome patients (MS). Anthropometric indices,
cardiovascular risk-score, and Mediterranean Diet Adherence (AMeDit) were
evaluated. Fasting glucose, glycosylated hemoglobin (HbA1c), and insulin were
measured. Insulin, GLP-1, and plasma DPP4 were determined within the first 30-min
postprandial period. Body-Mass-Index was significantly higher, and AMeDit was
significantly lower, but only in MS women. However, fasting glucose, HbA1c, and
postprandial insulin were significantly higher in MS men, but not in MS women.
Postprandial GLP-1 levels were lower in C men than in C women. Interestingly, in
comparison with controls, we found significant lower levels of plasma DPP4 in MS
women only. Moreover, negative lineal regressions were established between DPP4
activity with waist-to-hip ratio and cardiovascular risk-score, and positive
lineal regression with AMeDit. These results indicate gender differences in the
behavior of GLP-1 and DPP4 activity in MS, which could be relevant for its
treatment with GLP-1 analogues and DPP4 inhibitors.
PMID- 29958404
TI - Study on Hybrid Characteristics of Medicinally Used Cultivated Codonopsis Species
Using Ribosomal Internal Transcribed Spacer (ITS) Sequencing.
AB - Codonopsis taxa, as a traditional Chinese medicinal and edible plant, has found
expanding domestic and foreign applications in recent decades. However, the poor
management in germplasm resources market has inevitably caused an unnecessary
hybrid of the provenances. In order to clarify the hybrid characteristics of
germplasm resources in the main production area, the Codonopsis cultivars
collected from the provinces Gansu, Shannxi, Shanxi, and Hubei of China were
researched, using internal transcribed spacer (ITS) sequence technology. The
confirmation of additive nucleotides based on the ITS sequencing of polymerase
chain reaction (PCR) mixture was optimized and used to study the hybrid of
Codonopsis cultivars. The results showed that when the ratio of PCR mixture
increased up to 15 percent, the presence of a double peak in the sequencing
electrophoresis map could be confirmed, suggesting the existence of additive
nucleotides. According to the method above, 46 samples of Codonopsis cultivars
collected during 2016 and 2017 were studied and compared with the samples
collected from the year 2009 to 2010. All of the samples collected during 2016
and 2017 were hybridized and no genetic pure lines were found. In addition, the
sites of variable base reduced greatly, concentrating at positions 122 and/or
226. These phenomena suggested that the genetic diversity of Codonopsis cultivars
declined and the germplasm resources gradually converged. More attention should
be paid to the reasonable exploitation and genetic breeding of Codonopsis taxa.
PMID- 29958405
TI - Probe of Alcohol Structures in the Gas and Liquid States Using C-H Stretching
Raman Spectroscopy.
AB - Vibrational spectroscopy is a powerful tool for probing molecular structures and
dynamics since it offers a unique fingerprint that allows molecular
identification. One of important aspects of applying vibrational spectroscopy is
to develop the probes that can characterize the related properties of molecules
such as the conformation and intermolecular interaction. Many examples of
vibrational probes have appeared in the literature, including the azide group (
N3), amide group (-CONH2), nitrile groups (-CN), hydroxyl group (-OH), -CH group
and so on. Among these probes, the -CH group is an excellent one since it is
ubiquitous in organic and biological molecules and the C-H stretching vibrational
spectrum is extraordinarily sensitive to the local molecular environment.
However, one challenge encountered in the application of C-H probes arises from
the difficulty in the accurate assignment due to spectral congestion in the C-H
stretching region. In this paper, recent advances in the complete assignment of C
H stretching spectra of aliphatic alcohols and the utility of C-H vibration as a
probe of the conformation and weak intermolecular interaction are outlined. These
results fully demonstrated the potential of the -CH chemical group as a molecular
probe.
PMID- 29958406
TI - Processing Techniques for Bioresorbable Nanoparticles in Fabricating Flexible
Conductive Interconnects.
AB - Bioresorbable electronics (or transient electronics) devices can be potentially
used to replace build-to-last devices in consumer electronics, implantable
devices, and data security, leading to reduced electronic waste and surgical
processes through controllable dissolution. Recent development of printing
bioresorbable electronics leads to bioresorbable conductive pastes or inks that
can be used to make interconnects, circuit traces, and sensors, offering
alternative solutions for the predominant complementary metal oxide semiconductor
(CMOS) processes in fabrication of bioresorbable electronics. However, the
conductivities offered by current bioresorbable pastes and processing techniques
are still much lower than those of the bulk metals, demanding further improvement
in both paste composition and process optimization. This paper aims at exploring
several influential factors such as paste compositions and processing techniques
in determining conductivities of bioresorbable patterns. Experimental results
reveal that an optimized paste constituent with a ratio of
Zn:PVP:glycerol:methanol = 7:0.007:2:1 by weight can generate stable conductive
pastes suitable for a screen printing process. In addition, a high conductivity
of 60,213.6 S/m can be obtained by combining hot rolling and photonic sintering.
The results demonstrate that large-scale transient electronics can be obtained by
combining screen printing, hot rolling and photonic sintering approaches with
optimized paste compositions, offering important experimental proofs and
approaches for further improving the conductivity of bioresorbable pastes or inks
that can accommodate the demands for mass fabrication and practical use in
electronic industry.
PMID- 29958407
TI - Self-Reported Sleep Duration and Its Correlates with Sociodemographics, Health
Behaviours, Poor Mental Health, and Chronic Conditions in Rural Persons 40 Years
and Older in South Africa.
AB - This study aims to investigate sleep duration and its association with
sociodemographic, health behaviour, mental health, and chronic disease factors
among rural individuals 40 years and older in South Africa. Cross-sectional data
from the “Health and Aging in Africa: A Longitudinal Study of an INDEPTH
community in South Africa” (HAALSI) baseline survey were analysed. Socio
demographic, clinical, health, and sleep duration data were collected. The total
sample included 4725 persons 40 years and older (mean age 61.5 years, SD = 13.0,
age range of 40-111 years) in one sub-district in rural South Africa. The mean
sleep duration was 8.28 +/- 1.93 h. Short (<7 h) and long (≥9 h) sleepers
accounted for 13.1% and 40.0% of the sample, respectively. In adjusted
multinomial logistic regression, greater wealth status (p < 0.05), inadequate
fruit and vegetable consumption (p < 0.001), and depressive symptoms (p < 0.05)
were associated with a higher odds and physical inactivity (p < 0.05) with a
lower odds of short sleep duration. Being male (p < 0.001) and depressive
symptoms (p < 0.001) were associated with a higher odds and being 50 to 69 years
old (p < 0.01), having Grade 1 to 11 education (p < 0.05), and greater wealth
status (p < 0.001) were associated with a lower odds of long sleep duration. In
adjusted multinomial logistic regression, compared to normal sleepers, long
sleepers were more likely to have myocardial infarction (p < 0.05). In unadjusted
analysis, compared to normal sleepers, short sleepers were more likely to have
cataracts (p < 0.05). This study found that a significant proportion of rural
dwellers 40 years and older in South Africa had a short sleep duration and a high
proportion had a long sleep duration. Some associations, such as depression and
myocardial infarction, with short and/or long sleep duration were confirmed,
while no associations were found for many chronic conditions.
PMID- 29958409
TI - Evaluation of 2D Imaging Schemes for Pulsed Arterial Spin Labeling of the Human
Kidney Cortex.
AB - A number of imaging readout schemes are proposed for renal arterial spin labeling
(ASL) to quantify kidney cortex perfusion, including gradient echo-based methods
of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE
EPI), or spin echo-based schemes of spin-echo echo-planar imaging (SE-EPI) and
turbo spin-echo (TSE). Here, we compare these two-dimensional (2D) imaging
schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment
of human kidney cortex perfusion at 3 T. Ten healthy volunteers with normal renal
function were scanned using each 2D multi-slice imaging scheme, in combination
with a respiratory triggered flow-sensitive alternating inversion recovery (FAIR)
ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second
identical scan session within two weeks of the first scan session. Comparisons
were made between the imaging schemes in terms of perfusion-weighted image (PWI)
signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR),
spatial coverage, and repeatability. For each imaging scheme, the renal cortex
perfusion was calculated (bFFE: 276 +/- 29 mL/100g/min, GE-EPI: 222 +/- 18
mL/100g/min, SE-EPI: 201 +/- 36 mL/100g/min, and TSE: 200 +/- 20 mL/100g/min).
Perfusion was found to be higher for GE-based readouts when compared with SE
based readouts, with significantly higher measured perfusion for the bFFE readout
when compared with all other schemes (p < 0.05), attributed to the greater
vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI
when compared with all other schemes (p < 0.05), the SE-EPI readout gave the
highest tSNR, and was found to be the most reproducible scheme for the assessment
of kidney cortex, with a coefficient of variation (CoV) of 17.2%, whilst
minimizing variability of the perfusion-weighted signal across slices for whole
kidney perfusion assessment. For the assessment of kidney cortex perfusion using
2D readout schemes, SE-EPI provides optimal tSNR, minimal variability across
slices, and repeatable data acquired in a short scan time with low specific
absorption rate.
PMID- 29958410
TI - A New Conjugation Method Used for the Development of an Immunoassay for the
Detection of Amanitin, a Deadly Mushroom Toxin.
AB - One of the deadliest mushrooms is the death cap mushroom, Amanita phalloides. The
most toxic constituent is α-amanitin, a bicyclic octapeptide, which damages
the liver and kidneys. To develop a new tool for detecting this toxin, polyclonal
antibodies were generated and characterized. Both α- and β-amanitin
were coupled to carrier proteins through four different linking chemistries, one
of which has never before been described. These conjugates were evaluated for
their effectiveness in generating antibodies specific for the free toxin, as well
as their utility in formatting heterogeneous assays with high sensitivity.
Ultimately, these efforts yielded a newly described conjugation procedure
utilizing periodate oxidation followed by reductive amination that successfully
resulted in generating sensitive immunoassays (limit of detection (LOD), ~1.0
µg/L). The assays were characterized for their selectivity and were found
to equally detect α-, β-, and γ-amanitin, and not cross-react
with other toxins tested. Toxin detection in mushrooms was possible using a
simple sample preparation method. This enzyme-linked immunosorbent assay (ELISA)
is a simple and fast test, and readily detects amatoxins extracted from A.
phalloides.
PMID- 29958411
TI - Electrochemical Properties of Nitrate-Selective Electrodes: The Dependence of
Resistance on the Solution Concentration.
AB - The electrochemical properties of ion-exchanger-based solvent polymeric ion
selective electrodes (ISEs)—bulk and interfacial resistance, capacitance,
and polarization under a galvanostatic current step—are studied, with a
nitrate ISE based on tetradecylammonium nitrate (TDANO3) as a model system. The
study is performed by chronopotentiometric and impedance measurements, and
focuses on the dependence of the aforementioned properties on the concentration
of NO3− anions in solution. The impacts from the bulk and the interfacial
charge transfer to the overall membrane resistance are revealed. It is shown that
the bulk resistance of the membranes decreases over an increase of NO3−
concentration within the range of a Nernstian potentiometric response of the ISE.
This fact, also reported earlier for K+- and Ca2+-selective ISEs, is not in line
with current views of the mechanism of the ISE response, or of the role of ion
exchange in particular. The origin of this effect is unclear. Estimates are made
for the concentration of ionized species (NO3− and TDA+) and, respectively,
for the TDANO3 association constant, as well as for the species diffusion
coefficients in the membrane.
PMID- 29958408
TI - Molecular Aspects of Varicella-Zoster Virus Latency.
AB - Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and
the establishment of a lifelong latent infection in ganglionic neurons. VZV
reactivates in about one-third of infected individuals to cause herpes zoster,
often accompanied by neurological complications. The restricted host range of VZV
and, until recently, a lack of suitable in vitro models have seriously hampered
molecular studies of VZV latency. Nevertheless, recent technological advances
facilitated a series of exciting studies that resulted in the discovery of a VZV
latency-associated transcript (VLT) and provide novel insights into our
understanding of VZV latency and factors that may initiate reactivation. Deducing
the function(s) of VLT and the molecular mechanisms involved should now be
considered a priority to improve our understanding of factors that govern VZV
latency and reactivation. In this review, we summarize the implications of recent
discoveries in the VZV latency field from both a virus and host perspective and
provide a roadmap for future studies.
PMID- 29958412
TI - Neuroprotective Role of N-acetylcysteine against Learning Deficits and Altered
Brain Neurotransmitters in Rat Pups Subjected to Prenatal Stress.
AB - Prenatal adversaries like stress are known to harm the progeny and oxidative
stress, which is known to be one of the causative factors. N-acetyl cysteine
(NAC), which is a potent antioxidant, has been shown to play a neuroprotective
role in humans and experimental animals. This study examines the benefits of NAC
on the prenatal stress-induced learning and memory deficits and alteration in
brain neurotransmitter in rat pups. Pregnant dams were restrained (45 min; 3
times/day) during the early or late gestational period. Other groups received
early or late gestational restrain stress combined with NAC treatment throughout
the gestational period. At postnatal day (PND) 28, offspring were tested in a
shuttle box for assessing learning and memory, which was followed by a brain
neurotransmitter (dopamine, norepinephrine, and serotonin) estimation on PND 36.
Late gestational stress resulted in learning deficits, the inability to retain
the memory, and reduced brain dopamine content while not affecting norepinephrine
and serotonin. NAC treatment in prenatally stressed rats reversed learning and
memory deficits as well as brain dopamine content in offspring. These findings
suggest that NAC protect the progeny from an undesirable cognitive sequel
associated with prenatal stress.
PMID- 29958413
TI - Assessment of Commercially Available Immunoassays to Measure Glucocorticoid
Metabolites in African Grey Parrot (Psittacus Erithacus) Droppings: A Ready Tool
for Non-Invasive Monitoring of Stress.
AB - Despite being undomesticated, African Grey Parrots (Psittacus erithacus) are
commonly found in captivity, in zoos or as pets. Captivity can be an ongoing
stressor. Non-invasive glucocorticoid metabolites (GCM) measurements from bird
droppings are of interest for assessing stress but require careful evaluation in
each newly studied species. This study describes the assessment of such methods
for Psittacus erithacus to provide tools for evaluating stress and monitoring
welfare. We evaluated 12 method combinations of GCM extraction and enzyme
immunoassay (EIA) from a pool of African Grey Parrot droppings, through the
validation of several analytical parameters. Then, Heterophil: Lymphocyte Ratios
(HLR), another reliable stress marker, were determined and correlated to
individual dropping GCM concentrations for 29 birds to determine whether the
method is biologically relevant. We found that the best procedure to measure GCM
in African Grey Parrot droppings is a combination of 60% methanol extraction
measured using a Corticosterone EIA kit (Cayman Chemical Company) from fresh or
dry droppings. The establishment of a significant correlation (Pearson
coefficient correlation = 0.48; p = 0.0082) between HLR and GCM in the studied
population confirmed the method biological relevance. This method can thus be
applied to assess stress in Psittacus erithacus and support welfare monitoring in
zoo populations.
PMID- 29958414
TI - Loading IR820 Using Multifunctional Dendrimers with Enhanced Stability and
Specificity.
AB - Cyanine dyes are promising candidates in biomedical applications. Although
various delivery systems have been developed to enhance their properties, their
dendrimer-based delivery systems are seldom investigated. Herein, amine
terminated generation 5 poly(amidoamine) (G5.NH2) dendrimers and new indocyanine
green (IR820) dyes were chosen as models to study the loading ability of
dendrimers for cyanine dynes. G5.NH2 dendrimers were pre-modified with arginine
glycine-aspartic (RGD) peptides, poly(ethylene glycol) chains, and acetyl groups
to be endowed with cancer cell specificity and biocompatibility. The formed Ac-PR
dendrimers were used to load IR820, followed by thorough characterization. The
loaded number of IR820 was estimated to be 6.7 per dendrimer. The stability of
IR820 was improved through dendrimer loading, which was proved by their UV-vis
spectra under different kinds of storage conditions. In addition, the formed Ac
PR dendrimers can retain the loaded IR820 effectively. Their cytocompatibility
was desirable under the studied conditions. Their cellular uptake behaviors were
demonstrated to be enhanced by RGD modification, showing concentration-, co
incubation time-, and αvβ3 integrin receptor-dependent properties,
displaying a cytoplasm-location. The findings from this work demonstrated the
versatile loading and delivery capacity of dendrimers for near-infrared (NIR)
dyes, providing fundamental data for the development of dendrimer/NIR dye systems
for biomedical applications, especially for cancer theranostic applications.
PMID- 29958415
TI - Lutein and Zeaxanthin Isomers Protect against Light-Induced Retinopathy via
Decreasing Oxidative and Endoplasmic Reticulum Stress in BALB/cJ Mice.
AB - Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are the major
factors underlying photoreceptor degeneration. Lutein, RR-zeaxanthin
(3R,3’R-zeaxanthin) and RS (meso)-zeaxanthin (3R,3’S-RS- zeaxanthin)
(L/Zi) could protect against cell damage by ameliorating OS in retina. In this
study, we examined the effect of L/Zi supplementation in a mouse model of
photoreceptor degeneration and investigated whether the treatment of L/Zi
ameliorated OS and ERS. BALB/cJ mice after light exposure were used as the animal
model. The protective effects of L/Zi were observed by electroretinography (ERG)
and terminal deoxyuridine triphosphate nick-end labeling (TUNEL) analysis. The
underlying mechanisms related to OS and ERS were explored by Western blotting.
After L/Zi treatment, the ERG amplitudes were significantly higher, and the
number of TUNEL-positive cells was significantly reduced compared to that of the
vehicle group. Western blotting results revealed that OS was ameliorated
according to the significant downregulation of phosphorylated c-Jun N-terminal
kinase (p-JNK), and significant upregulation of nuclear factor erythroid 2
related factor 2 (Nrf2). In addition, ERS was reduced according to the
significant downregulation of 78 kDa glucose-regulated protein (GRP78),
phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK),
activating transcription factor 4 (ATF4) and activating transcription factor
(ATF6). Our data shows that L/Zi provided functional and morphological
preservation of photoreceptors against light damage, which is probably related to
its mitigation of oxidative and endoplasmic reticulum stress.
PMID- 29958416
TI - Caffeic Acid Targets AMPK Signaling and Regulates Tricarboxylic Acid Cycle
Anaplerosis while Metformin Downregulates HIF-1alpha-Induced Glycolytic Enzymes
in Human Cervical Squamous Cell Carcinoma Lines.
AB - The small molecules, natural antioxidant Caffeic Acid (trans-3,4
Dihydroxycinnamic acid CA) and anti-diabetic drug Metformin (Met), activate
5′-adenosine monophosphate-activated protein kinase (AMPK) and interfere
with metabolic reprogramming in human cervical squamous carcinoma cells. Here, to
gain more insight into the ability of CA, Met and the combination of both
compounds to impair aerobic glycolysis (the “Warburg effect”) and
disrupt bioenergetics of cancer cells, we employed the cervical tumor cell lines
C-4I and HTB-35/SiHa. In epithelial C-4I cells derived from solid tumors, CA
alleviated glutamine anaplerosis by downregulation of Glutaminase (GLS) and Malic
Enzyme 1 (ME1), which resulted in the reduction of NADPH levels. CA treatment of
the cells altered tricarboxylic acid (TCA) cycle supplementation with pyruvate
via Pyruvate Dehydrogenase Complex (PDH), increased ROS formation and enhanced
cell death. Additionally, CA and CA/Met evoked intracellular energetic stress,
which was followed by activation of AMPK and the impairment of unsaturated FA de
novo synthesis. In invasive HTB-35 cells, Met inhibited Hypoxia-inducible Factor
1 (HIF-1α) and suppressed the expression of the proteins involved in the
“Warburg effect”, such as glucose transporters (GLUT1, GLUT3) and
regulatory enzymes of glycolytic pathway Hexokinase 2 (HK2), 6-Phosphofructo-2
Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4), Pyruvate Kinase (PKM) and Lactate
Dehydrogenase A (LDH). Met suppressed the expression of c-Myc, BAX and cyclin-D1
(CCND1) and evoked apoptosis in HTB-35 cells. In conclusion, both small molecules
CA and Met are capable of disrupting energy homeostasis, regulating oxidative
metabolism/glycolysis in cervical tumor cells in regard to specific metabolic
phenotype of the cells. CA and Met may provide a promising approach in the
prevention of cervical cancer progression.
PMID- 29958417
TI - Farnesoid X Receptor Activation Enhances Transforming Growth Factor beta-Induced
Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells.
AB - Farnesoid X receptor (FXR) is a receptor for bile acids and plays an important
role in the regulation of bile acid metabolism in the liver. Although FXR has
been shown to affect hepatocarcinogenesis through both direct and indirect
mechanisms, potential roles of FXR in epithelial-mesenchymal transition (EMT) in
hepatocellular carcinoma (HCC) remain unclear. We examined the effect of several
FXR ligands on EMT-related morphological changes in HCC cell lines, such as HuH-7
and Hep3B cells. FXR agonists (chenodeoxycholic acid, GW4064, and obeticholic
acid)—but not an antagonist (guggulsterone)—induced actin
polymerization and expression of N-cadherin and phosphorylated focal adhesion
kinase, although they were less effective than transforming growth factor β
(TGF-β). FXR agonist treatment enhanced TGF-β-induced EMT morphologic
changes and FXR antagonist inhibited the effect of TGF-β. Thus, FXR
activation enhances EMT in HCC and FXR antagonists may be EMT-suppressing drug
candidates.
PMID- 29958418
TI - A Promising Method of Typhoon Wave Retrieval from Gaofen-3 Synthetic Aperture
Radar Image in VV-Polarization.
AB - The motivation of this work is to explore the possibility of typhoon wave
retrieval (the main parameter is significant wave height (SWH)) for C-band Gaofen
(GF-3) synthetic aperture radar (SAR) with a wide swath coverage (>400 km). We
aim to establish an analysis of a typhoon wave in the subresolution-scale
(approximately 20 × 20 km2) on GF-3 SAR through SAR-measured parameters,
including a normalized radar cross section (NRCS) and variance of the normalized
SAR image (herein called cvar), which are the basic variables in an empirical
wave retrieval algorithm and are independent of visible wave streaks. Several
typhoons around the China Seas were captured by Chinese GF-3 SAR in 2017; e.g.,
Noru, Doksuri, Talim and Hato. The wave fields simulated from the third
generation numerical wave model WAVEWATCH-III (WW3) are collocated with these
images. In general, the distribution patterns of the typhoon waves from the WW3
model are consistent with wave fields from the European Centre for Medium-Range
Weather Forecasts (ECMWF) at 0.125° grids, indicating that the simulation
results from the WW3 model are suitable for our study. In addition to winds
retrieved from GF-3 SAR images in vertical-horizontal (VH) polarization, the
characteristics of the typhoon wave on vertical-vertical (VV) polarization GF-3
SAR images are studied. It is found that SWH has a linear relationship with NRCS
and cvar, however, SWH fluctuates with wind speed at all incidence angles. Based
on the analyzed results, we simply tune two empirical wave retrieval algorithms
for GF-3 SAR in typhoons. Although the correlation (COR) reaches 0.5 taking
account into the NRCS term, a more accurate retrieval algorithm, including more
related terms, is anticipated for further development for GF-3 SAR and validated
through more typhoon images.
PMID- 29958419
TI - FluoSpec 2-An Automated Field Spectroscopy System to Monitor Canopy Solar-Induced
Fluorescence.
AB - Accurate estimation of terrestrial photosynthesis has broad scientific and
societal impacts. Measurements of photosynthesis can be used to assess plant
health, quantify crop yield, and determine the largest CO2 flux in the carbon
cycle. Long-term and continuous monitoring of vegetation optical properties can
provide valuable information about plant physiology. Recent developments of the
remote sensing of solar-induced chlorophyll fluorescence (SIF) and vegetation
spectroscopy have shown promising results in using this information to quantify
plant photosynthetic activities and stresses at the ecosystem scale. However,
there are few automated systems that allow for unattended observations over
months to years. Here we present FluoSpec 2, an automated system for collecting
irradiance and canopy radiance that has been deployed in various ecosystems in
the past years. The instrument design, calibration, and tests are recorded in
detail. We discuss the future directions of this field spectroscopy system. A
network of SIF sensors, FluoNet, is established to measure the diurnal and
seasonal variations of SIF in several ecosystems. Automated systems such as
FluoSpec 2 can provide unique information on ecosystem functioning and provide
important support to the satellite remote sensing of canopy photosynthesis.
PMID- 29958420
TI - Current State of Pediatric Heart Failure.
AB - Pediatric heart failure (HF) represents an important cause of morbidity and
mortality in childhood. There is an overlapping relationship of HF, congenital
heart disease, and cardiomyopathy. The goal of treatment of HF in children is to
maintain stability, prevent progression, and provide a reasonable milieu to allow
somatic growth and optimal development. Current management and therapy for HF in
children are extrapolated from treatment approaches in adults. There are
significant barriers in applying adult data to children because of developmental
factors, age variation from birth to adolescence, and differences in the genetic
expression profile and β-adrenergic signaling. At the same time, there are
significant challenges in performing well-designed drug trials in children with
HF because of heterogeneity of diagnoses identifying a clinically relevant
outcome with a high event rate, and a difficulty in achieving sufficient
enrollment. A judicious balance between extrapolation from adult HF guidelines
and the development of child-specific data on treatment represent a wise approach
to optimize pediatric HF management. This approach is helpful as reflected by the
increasing role of ventricular assist devices in the management of advanced HF in
children. This review discusses the causes, epidemiology, pathophysiology,
clinical manifestations, conventional medical treatment, clinical trials, and the
role of device therapy in pediatric HF.
PMID- 29958421
TI - A Physiologically-Based Pharmacokinetic Modeling Approach Using Biomonitoring
Data in Order to Assess the Contribution of Drinking Water for the Achievement of
an Optimal Fluoride Dose for Dental Health in Children.
AB - Due to an optimal fluoride concentration in drinking water advised for caries
prevention purposes, the population is now exposed to multiple sources of
fluoride. The availability of population biomonitoring data currently allow us to
evaluate the magnitude of this exposure. The objective of this work was,
therefore, to use such data in order to estimate whether community water
fluoridation still represents a significant contribution toward achieving a
suggested daily optimal fluoride (external) intake of 0.05 mg/kg/day. Therefore,
a physiologically-based pharmacokinetic model for fluoride published in the
literature was used and adapted in Excel for a typical 4-year-old and 8-year-old
child. Biomonitoring data from the Canadian Health Measures Survey among people
living in provinces with very different drinking water fluoridation coverage
(Quebec, 2.5%; Ontario, 70% of the population) were analyzed using this adapted
model. Absorbed doses for the 4-year-old and 8-year-old children were,
respectively, 0.03 mg/kg/day and 0.02 mg/kg/day in Quebec and of 0.06 mg/kg/day
and 0.05 mg/kg/day in Ontario. These results show that community water
fluoridation contributes to increased fluoride intake among children, which leads
to reaching, and in some cases even exceeding, the suggested optimal absorbed
dose of 0.04 mg/kg/day, which corresponds to the suggested optimal fluoride
intake mentioned above. In conclusion, this study constitutes an incentive to
further explore the multiple sources of fluoride intake and suggests that a new
balance between them including drinking water should be examined in accordance
with the age-related physiological differences that influence fluoride
metabolism.
PMID- 29958422
TI - Lysoquinone-TH1, a New Polyphenolic Tridecaketide Produced by Expressing the
Lysolipin Minimal PKS II in Streptomyces albus.
AB - The structural repertoire of bioactive naphthacene quinones is expanded by
engineering Streptomyces albus to express the lysolipin minimal polyketide
synthase II (PKS II) genes from Streptomyces tendae Tü 4042 (llpD-F) with
the corresponding cyclase genes llpCI-CIII. Fermentation of the recombinant
strain revealed the two new polyaromatic tridecaketides lysoquinone-TH1 (7,
identified) and TH2 (8, postulated structure) as engineered congeners of the
dodecaketide lysolipin (1). The chemical structure of 7, a benzo[a]naphthacene
8,13-dione, was elucidated by NMR and HR-MS and confirmed by feeding experiments
with [1,2-13C2]-labeled acetate. Lysoquinone-TH1 (7) is a pentangular polyphenol
and one example of such rare extended polyaromatic systems of the
benz[a]napthacene quinone type produced by the expression of a minimal PKS II in
combination with cyclases in an artificial system. While the natural product
lysolipin (1) has antimicrobial activity in nM-range, lysoquinone-TH1 (7) showed
only minor potency as inhibitor of Gram-positive microorganisms. The bioactivity
profiling of lysoquinone-TH1 (7) revealed inhibitory activity towards
phosphodiesterase 4 (PDE4), an important target for the treatment in human health
like asthma or chronic obstructive pulmonary disease (COPD). These results
underline the availability of pentangular polyphenolic structural skeletons from
biosynthetic engineering in the search of new chemical entities in drug
discovery.
PMID- 29958423
TI - Synthesis of Antibacterial Nisin-Peptoid Hybrids Using Click Methodology.
AB - Antimicrobial peptides and structurally related peptoids offer potential for the
development of new antibiotics. However, progress has been hindered by challenges
presented by poor in vivo stability (peptides) or lack of selectivity (peptoids).
Herein, we have developed a process to prepare novel hybrid antibacterial agents
that combine both linear peptoids (increased in vivo stability compared to
peptides) and a nisin fragment (lipid II targeting domain). The hybrid nisin
peptoids prepared were shown to have low micromolar activity (comparable to
natural nisin) against methicillin-resistant Staphylococcus aureus.
PMID- 29958425
TI - Identity and Seasonal Abundance of Beneficial Arthropods Associated with Big
Sagebrush (Artemisia tridentata) in Central Washington State, USA.
AB - Big sagebrush (Artemisia tridentata) characterizes and dominates the sagebrush
steppe, the largest temperate semi-desert ecosystem in North America. The
beneficial arthropod fauna hosted by A. tridentata is poorly known but could be
of importance to nearby agriculture seeking to exploit biologically-based pest
management. Over four years, we identified and assessed the seasonal abundance of
beneficial arthropods (predators, parasitoids, pollinators) associated with A.
tridentata during spring to autumn in the Yakima Valley of central Washington
using sticky traps. During 2011-2014, 207 sticky traps were placed on non
blooming and blooming A. tridentata plants for a total of 966 trapping days.
Overall, across all seasons, we trapped 259.7 beneficial arthropods per trap and
92% of these were parasitoid wasps. Significantly greater numbers of beneficial
arthropods were associated with blooming A. tridentata during autumn (410/trap)
than non-blooming plants in the spring (181.3/trap) or summer (85.1/trap).
Parasitoid wasps and predatory true bugs were most abundant during the autumn,
but ladybeetles, lacewings, spiders, bees, and predatory thrips were most common
during spring. The association of high numbers of predators, parasitoids, and
pollinators with A. tridentata during blooming and non-blooming periods indicates
that this plant is an important reservoir of beneficial arthropods in the
sagebrush steppe of central Washington. Consequently, biologically-based pest
management programs in central Washington may benefit from careful management and
retention of A. tridentata plants on crop borders.
PMID- 29958424
TI - Anti-Correlation between the Dynamics of the Active Site Loop and C-Terminal Tail
in Relation to the Homodimer Asymmetry of the Mouse Erythroid 5-Aminolevulinate
Synthase.
AB - Biosynthesis of heme represents a complex process that involves multiple stages
controlled by different enzymes. The first of these proteins is a pyridoxal
5′-phosphate (PLP)-dependent homodimeric enzyme, 5-aminolevulinate synthase
(ALAS), that catalyzes the rate-limiting step in heme biosynthesis, the
condensation of glycine with succinyl-CoA. Genetic mutations in human erythroid
specific ALAS (ALAS2) are associated with two inherited blood disorders, X-linked
sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP). XLSA is caused by
diminished ALAS2 activity leading to decreased ALA and heme syntheses and
ultimately ineffective erythropoiesis, whereas XLPP results from “gain-of
function” ALAS2 mutations and consequent overproduction of protoporphyrin
IX and increase in Zn2+-protoporphyrin levels. All XLPP-linked mutations affect
the intrinsically disordered C-terminal tail of ALAS2. Our earlier molecular
dynamics (MD) simulation-based analysis showed that the activity of ALAS2 could
be regulated by the conformational flexibility of the active site loop whose
structural features and dynamics could be changed due to mutations. We also
revealed that the dynamic behavior of the two protomers of the ALAS2 dimer
differed. However, how the structural dynamics of ALAS2 active site loop and C
terminal tail dynamics are related to each other and contribute to the homodimer
asymmetry remained unanswered questions. In this study, we used bioinformatics
and computational biology tools to evaluate the role(s) of the C-terminal tail
dynamics in the structure and conformational dynamics of the murine ALAS2
homodimer active site loop. To assess the structural correlation between these
two regions, we analyzed their structural displacements and determined their
degree of correlation. Here, we report that the dynamics of ALAS2 active site
loop is anti-correlated with the dynamics of the C-terminal tail and that this
anti-correlation can represent a molecular basis for the functional and dynamic
asymmetry of the ALAS2 homodimer.
PMID- 29958426
TI - Effect of Nanoparticle Morphology on Pre-Breakdown and Breakdown Properties of
Insulating Oil-Based Nanofluids.
AB - Nanoparticles currently in use are challenged in further improving the dielectric
strength of insulating oil. There is a great need for a new type of nanoparticle
to promote the application of insulating oil-based nanofluids in electric
industries. This paper experimentally investigates the effect of nanoparticle
morphology on pre-breakdown and breakdown properties of insulating oil-based
nanofluids. The positive impulse breakdown voltage of insulating oil can be
significantly increased by up to 55.5% by the presence of TiO2 nanorods, up to
1.23 times that of TiO2 nanospheres. Pre-breakdown streamer propagation
characteristics reveal that streamer discharge channels turn into a bush-like
shape with much denser and shorter branches in the nanofluid with TiO2 nanorods.
Moreover, the propagation velocity of streamers is dramatically decreased to
34.7% of that in the insulating oil. The greater improvement of nanorods on the
breakdown property can be attributed to the lower distortion of the electric
field. Thus, when compared with nanospheres, pre-breakdown streamer propagation
of nanofluid is much more suppressed with the addition of nanorods, resulting in
a greater breakdown voltage.
PMID- 29958428
TI - The Effect of Zn Content on the Mechanical Properties of Mg-4Nd-xZn Alloys (x =
0, 3, 5 and 8 wt.%).
AB - The mechanical properties of as-cast Mg-4Nd-xZn (x = 0, 3, 5 or 8 wt.%) alloys
were investigated both in situ and ex situ in as-cast and solution-treated
conditions. The additions of 3 or 5 wt.% Zn in the base Mg-4Nd alloy did not
improve yield strength in comparison to the binary Mg-4Nd alloy. Mechanical
properties were shown to improve only with the relatively high concentration of 8
wt.% Zn to Mg-4Nd. The change in intermetallic morphology from a continuous
intermetallic to a lamella-like intermetallic was the primary reason for the
decreased mechanical properties in Mg-4Nd-3Zn and Mg-4Nd-5Zn compared with Mg-4Nd
and Mg-4Nd-8Zn. The dissolution of intermetallic at grain boundaries following
heat treatment further indicated the importance of grain boundary reinforcement
as shown in both in situ and ex situ compression testing. Azimuthal angle-time
plots indicated little grain rotation most noticeably in Mg-4Nd, which also
indicated the influence of a strong intermetallic network along the grain
boundaries.
PMID- 29958429
TI - Local Melting of Gold Thin Films by Femtosecond Laser-Interference Processing to
Generate Nanoparticles on a Source Target.
AB - Shape- and size-controlled metallic nanoparticles are very important due to their
wide applicability. Such particles have been fabricated by chemosynthesis,
chemical-vapor deposition, and laser processing. Pulsed-laser deposition and
laser-induced dot transfer use ejections of molten layers and solid-liquid-solid
processes to fabricate nanoparticles with a radius of some tens to hundreds of
nm. In these processes, the nanoparticles are collected on an acceptor substrate.
In the present experiment, we used laser-interference processing of gold thin
films, which deposited nanoparticles directly on the source thin film with a
yield ratio. A typical nanoparticle had roundness fr=0.99 and circularity
fcirc=0.869, and the radius was controllable between 69 and 188 nm. The smallest
radius was 82 nm on average, and the smallest standard deviation was 3 nm. The
simplicity, high yield, and ideal features of the nanoparticles produced by this
method will broaden the range of applications of nanoparticles in fields such as
plasmonics.
PMID- 29958427
TI - Iron Oxide Nanoparticles in Photothermal Therapy.
AB - Photothermal therapy is a kind of therapy based on increasing the temperature of
tumoral cells above 42 °C. To this aim, cells must be illuminated with a
laser, and the energy of the radiation is transformed in heat. Usually, the
employed radiation belongs to the near-infrared radiation range. At this range,
the absorption and scattering of the radiation by the body is minimal. Thus,
tissues are almost transparent. To improve the efficacy and selectivity of the
energy-to-heat transduction, a light-absorbing material, the photothermal agent,
must be introduced into the tumor. At present, a vast array of compounds are
available as photothermal agents. Among the substances used as photothermal
agents, gold-based compounds are one of the most employed. However, the undefined
toxicity of this metal hinders their clinical investigations in the long run.
Magnetic nanoparticles are a good alternative for use as a photothermal agent in
the treatment of tumors. Such nanoparticles, especially those formed by iron
oxides, can be used in combination with other substances or used themselves as
photothermal agents. The combination of magnetic nanoparticles with other
photothermal agents adds more capabilities to the therapeutic system: the
nanoparticles can be directed magnetically to the site of interest (the tumor)
and their distribution in tumors and other organs can be imaged. When used alone,
magnetic nanoparticles present, in theory, an important limitation: their molar
absorption coefficient in the near infrared region is low. The controlled
clustering of the nanoparticles can solve this drawback. In such conditions, the
absorption of the indicated radiation is higher and the conversion of energy in
heat is more efficient than in individual nanoparticles. On the other hand, it
can be designed as a therapeutic system, in which the heat generated by magnetic
nanoparticles after irradiation with infrared light can release a drug attached
to the nanoparticles in a controlled manner. This form of targeted drug delivery
seems to be a promising tool of chemo-phototherapy. Finally, the heating
efficiency of iron oxide nanoparticles can be increased if the infrared radiation
is combined with an alternating magnetic field.
PMID- 29958430
TI - The Arabidopsis Calcium-Dependent Protein Kinases (CDPKs) and Their Roles in
Plant Growth Regulation and Abiotic Stress Responses.
AB - As a ubiquitous secondary messenger in plant signaling systems, calcium ions
(Ca2+) play essential roles in plant growth and development. Within the cellular
signaling network, the accurate decoding of diverse Ca2+ signal is a fundamental
molecular event. Calcium-dependent protein kinases (CDPKs), identified commonly
in plants, are a kind of vital regulatory protein deciphering calcium signals
triggered by various developmental and environmental stimuli. This review chiefly
introduces Ca2+ distribution in plant cells, the classification of Arabidopsis
thaliana CDPKs (AtCDPKs), the identification of the Ca2+-AtCDPK signal
transduction mechanism and AtCDPKs’ functions involved in plant growth
regulation and abiotic stress responses. The review presents a comprehensive
overview of AtCDPKs and may contribute to the research of CDPKs in other plants.
PMID- 29958431
TI - Simultaneous Quantification of Three Curcuminoids and Three Volatile Components
of Curcuma longa Using Pressurized Liquid Extraction and High-Performance Liquid
Chromatography.
AB - A high-performance liquid chromatography (HPLC) method was investigated for the
simultaneous quantification of two chemical types of bioactive compounds in the
rhizome of Curcuma longa Linn. (turmeric), including three curcuminoids:
Curcumin, bisdemethoxycurcumin, and demethoxycurcumin; and three volatile
components: ar-turmerone, β-turmerone, and α-turmerone. In the present
study, the sample extraction system was optimized by a pressurized liquid
extraction (PLE) process for further HPLC analysis. The established HPLC analysis
conditions were achieved using a Zorbax SB-C18 column (250 mm × 4.6 mm
i.d., 5 μm) and a gradient mobile phase comprised of acetonitrile and 0.4%
(v/v) aqueous acetic acid with an eluting rate of 1.0 mL/min. The curcuminoids
and volatile components were detected at 430 nm and 240 nm, respectively.
Moreover, the method was validated in terms of linearity, sensitivity, precision,
stability and accuracy. The validated method was successfully applied to evaluate
the quality of twelve commercial turmeric samples.
PMID- 29958432
TI - Enhanced Hydrogen Detection Based on Mg-Doped InN Epilayer.
AB - It is a fact that surface electron accumulation layer with sheet electron density
in the magnitude of ~1013 cm−2 on InN, either as-grown or Mg-doped, makes
InN an excellent candidate for sensing application. In this paper, the response
of hydrogen sensors based on Mg-doped InN films (InN:Mg) grown by molecular beam
epitaxy has been investigated. The sensor exhibits a resistance variation ratio
of 16.8% with response/recovery times of less than 2 min under exposure to 2000
ppm H2/air at 125 °C, which is 60% higher in the magnitude of response than
the one based on the as-grown InN film. Hall-effect measurement shows that the
InN:Mg with suitable Mg doping level exhibits larger sheet resistance, which
accords with buried p-type conduction in the InN bulk. This work shows the
advantage of InN:Mg and signifies its potential for sensing application.
PMID- 29958434
TI - Feature Selection via Swarm Intelligence for Determining Protein Essentiality.
AB - Protein essentiality is fundamental to comprehend the function and evolution of
genes. The prediction of protein essentiality is pivotal in identifying disease
genes and potential drug targets. Since the experimental methods need many
investments in time and funds, it is of great value to predict protein
essentiality with high accuracy using computational methods. In this study, we
present a novel feature selection named Elite Search mechanism-based Flower
Pollination Algorithm (ESFPA) to determine protein essentiality. Unlike other
protein essentiality prediction methods, ESFPA uses an improved swarm
intelligence-based algorithm for feature selection and selects optimal features
for protein essentiality prediction. The first step is to collect numerous
features with the highly predictive characteristics of essentiality. The second
step is to develop a feature selection strategy based on a swarm intelligence
algorithm to obtain the optimal feature subset. Furthermore, an elite search
mechanism is adopted to further improve the quality of feature subset.
Subsequently a hybrid classifier is applied to evaluate the essentiality for each
protein. Finally, the experimental results show that our method is competitive to
some well-known feature selection methods. The proposed method aims to provide a
new perspective for protein essentiality determination.
PMID- 29958435
TI - FaceLooks: A Smart Headband for Signaling Face-to-Face Behavior.
AB - Eye-to-eye contact and facial expressions are key communicators, yet there has
been little done to evaluate the basic properties of face-to-face; mutual head
orientation behaviors. This may be because there is no practical device available
to measure the behavior. This paper presents a novel headband-type wearable
device called FaceLooks, used for measuring the time of the face-to-face state
with identity of the partner, using an infrared emitter and receiver. It can also
be used for behavioral healthcare applications, such as for children with
developmental disorders who exhibit difficulties with the behavior, by providing
awareness through the visual feedback from the partner’s device. Two
laboratory experiments showed the device’s detection range and response
time, tested with a pair of dummy heads. Another laboratory experiment was done
with human participants with gaze trackers and showed the device’s
substantial agreement with a human observer. We then conducted two field studies
involving children with intellectual disabilities and/or autism spectrum
disorders. The first study showed that the devices could be used in the school
setting, observing the children did not remove the devices. The second study
showed that the durations of children’s face-to-face behavior could be
increased under a visual feedback condition. The device shows its potential to be
used in therapy and experimental fields because of its wearability and its
ability to quantify and shape face-to-face behavior.
PMID- 29958433
TI - MicroRNA Control of TGF-beta Signaling.
AB - Transcriptional and post-transcriptional regulation shapes the transcriptome and
proteome changes induced by various cellular signaling cascades. MicroRNAs
(miRNAs) are small regulatory RNAs that are approximately 22 nucleotides long,
which direct the post-transcriptional regulation of diverse target genes and
control cell states. Transforming growth factor (TGF)-β family is a
multifunctional cytokine family, which plays many regulatory roles in the
development and pathogenesis of diverse diseases, including fibrotic disease,
cardiovascular disease and cancer. Previous studies have shown that the TGF
β pathway includes the miRNA pathway as an important component of its
downstream signaling cascades. Multiple studies of epithelial-mesenchymal
transition (EMT)-related miRNAs have highlighted that miRNAs constitute the
intrinsic bistable molecular switches of cell states by forming double negative
feedback loops with EMT-inducing transcription factors. This may be important for
understanding the reversibility of EMT at the single-cell level, the presence of
distinct EMT transition states and the intra- and inter-tumor heterogeneity of
cancer cell phenotypes. In the present review, I summarize the connection between
TGF-β signaling and the miRNA pathway, placing particular emphasis on the
regulation of miRNA expression by TGF-β signaling, the modulation of TGF
β signaling by miRNAs, the miRNA-mediated modulation of EMT and endothelial
mesenchymal transition as well as the crosstalk between miRNA and TGF-β
pathways in the tumor microenvironment.
PMID- 29958436
TI - Research on Mechanisms and Controlling Methods of Macro Defects in TC4 Alloy
Fabricated by Wire Additive Manufacturing.
AB - Wire feeding additive manufacturing (WFAM) has broad application prospects
because of its advantages of low cost and high efficiency. However, with the mode
of lateral wire feeding, including wire and laser additive manufacturing, gas
tungsten arc additive manufacturing etc., it is easy to generate macro defects on
the surface of the components because of the anisotropy of melted wire, which
limits the promotion and application of WFAM. In this work, gas tungsten arc
additive manufacturing with lateral wire feeding is proposed to investigate the
mechanisms of macro defects. The results illustrate that the defect forms mainly
include side spatters, collapse, poor flatness, and unmelted wire. It was found
that the heat input, layer thickness, tool path, and wire curvature can have an
impact on the macro defects. Side spatters are the most serious defects, mainly
because the droplets cannot be transferred to the center of the molten pool in
the lateral wire feeding mode. This research indicates that the macro defects can
be controlled by optimizing the process parameters. Finally, block parts without
macro defects were fabricated, which is meaningful for the further application of
WFAM.
PMID- 29958438
TI - Using Interpretative Structural Modeling to Identify Critical Success Factors for
Safety Management in Subway Construction: A China Study.
AB - With the rapid development of urbanization in China, a vast number of subway
projects are under construction and planned in many cities. However, the
complexities of the environment in subway construction inherently bring about
many uncertainties and risk factors. Understanding the inherent properties of the
critical success factors (CSFs) will contribute significantly to the subway
construction. From this perspective, this paper aims to identify the CSFs for
safety management in subway construction. This study screened preliminary CSFs
through a literature review and in-depth interviews with experts in China. Based
on the data gathered and subsequently analyzed from the questionnaire surveys, a
final total of 24 CSFs were identified. Then, interpretative structural modeling
was employed to ascertain the interrelations among them. The result showed that
the factors concerning the engineering survey and design not only occupy
relatively higher scores in the questionnaire survey but also contribute
significantly latent impacts on other factors. In addition, the creation of a
reasonable schedule and the investment of the safety measures were also found to
have a fundamental impact on the safety management of subway construction. This
research guided the safety managers in determining the most important safety
factors they must face and provided them valuable information that could promote
safety performance and decrease the number of accidents over the course of subway
construction.
PMID- 29958437
TI - Drug Delivery Systems from Self-Assembly of Dendron-Polymer Conjugates ?.
AB - This review highlights the utilization of dendron-polymer conjugates as building
blocks for the fabrication of nanosized drug delivery vehicles. The examples
given provide an overview of the evolution of these delivery platforms, from
simple micellar containers to smart stimuli- responsive drug delivery systems
through their design at the macromolecular level. Variations in chemical
composition and connectivity of the dendritic and polymeric segments provide a
variety of self-assembled micellar nanostructures that embody desirable
attributes of viable drug delivery systems.
PMID- 29958440
TI - Warfarin: The End or the End of One Size Fits All Therapy?
AB - Oral anticoagulants are required for both treatment and prophylaxis in many
different diseases. Clinicians and patients now have a choice of oral
anticoagulants, including the vitamin K antagonists (of which warfarin is the
most widely used and is used as the exemplar in this paper), and direct oral
anticoagulants (DOACs: dabigatran, apixaban, rivaroxaban, and edoxaban). This
paper explores the recent advances and controversies in oral anticoagulation.
While some commentators may favour a complete switchover to DOACs, this paper
argues that warfarin still has a place in therapy, and a stratified approach that
enables the correct choice of both drug and dose would improve both patient
outcomes and affordability.
PMID- 29958441
TI - Design and Evaluation of FBG-Based Tension Sensor in Laparoscope Surgical Robots.
AB - Due to the narrow space and a harsh chemical environment in the sterilization
processes for the end-effector of surgical robots, it is difficult to install and
integrate suitable sensors for the purpose of effective and precise force
control. This paper presents an innovative tension sensor for estimation of
grasping force in our laparoscope surgical robot. The proposed sensor measures
the tension of cable using fiber gratings (FBGs) which are pasted in the grooves
on the inclined cantilevers of the sensor. By exploiting the stain measurement
characteristics of FBGs, the small deformation of the inclined cantilevers caused
by the cable tension can be measured. The working principle and the sensor model
are analyzed. Based on the sensor model, the dimensions of the sensor are
designed and optimized. A dedicated experimental setup is established to
calibrate and test the sensor. The results of experiments for estimation the
grasping force validate the sensor.
PMID- 29958439
TI - Cosmetics Preservation: A Review on Present Strategies.
AB - Cosmetics, like any product containing water and organic/inorganic compounds,
require preservation against microbial contamination to guarantee
consumer’s safety and to increase their shelf-life. The microbiological
safety has as main goal of consumer protection against potentially pathogenic
microorganisms, together with the product’s preservation resulting from
biological and physicochemical deterioration. This is ensured by chemical,
physical, or physicochemical strategies. The most common strategy is based on the
application of antimicrobial agents, either by using synthetic or natural
compounds, or even multifunctional ingredients. Current validation of a
preservation system follow the application of good manufacturing practices
(GMPs), the control of the raw material, and the verification of the preservative
effect by suitable methodologies, including the challenge test. Among the
preservatives described in the positive lists of regulations, there are parabens,
isothiasolinone, organic acids, formaldehyde releasers, triclosan, and
chlorhexidine. These chemical agents have different mechanisms of antimicrobial
action, depending on their chemical structure and functional group’s
reactivity. Preservatives act on several cell targets; however, they might
present toxic effects to the consumer. Indeed, their use at high concentrations
is more effective from the preservation viewpoint being, however, toxic for the
consumer, whereas at low concentrations microbial resistance can develop.
PMID- 29958442
TI - Threshold-Based Noise Detection and Reduction for Automatic Speech Recognition
System in Human-Robot Interactions.
AB - This work develops a speech recognition system that uses two procedures of
proposed noise detection and combined noise reduction. The system can be used in
applications that require interactive robots to recognize the contents of speech
that includes ambient noise. The system comprises two stages, which are the
threshold-based noise detection and the noise reduction procedure. In the first
stage, the proposed system automatically determines when to enhance the quality
of speech based on the signal-to-noise ratio (SNR) values of the collected speech
at all times. In the second stage, independent component analysis (ICA) and
subspace speech enhancement (SSE) are employed for noise reduction. Experimental
results reveal that the SNR values of the enhanced speech exceed those of the
received noisy speech by approximately 20 dB to 25 dB. The noise reduction
procedure improves the speech recognition rates by around 15% to 25%. The
experimental results indicate that the proposed system can reduce the effect of
noise in numerous noisy environments and improve the quality of speech for
recognition purposes.
PMID- 29958444
TI - Microencapsulation and the Characterization of Polyherbal Formulation (PHF) Rich
in Natural Polyphenolic Compounds.
AB - Microencapsulation of polyherbal formulation (PHF) extract was carried out by
freeze drying method, by employing gum arabic (GA), gelatin (GE), and
maltodextrin (MD) with their designated different combinations as encapsulating
wall materials. Antioxidant components (i.e., total phenolic contents (TPC),
total flavonoids contents (TFC), and total condensed tannins (TCT)), antioxidant
activity (i.e., DPPH, β-carotene & ABTS+ assays), moisture contents, water
activity (aw), solubility, hygroscopicity, glass transition temperature (Tg),
particle size, morphology, in vitroα-amylase and α-glucosidase
inhibition and bioavailability ratios of the powders were investigated. Amongst
all encapsulated products, TB (5% GA & 5% MD) and TC (10% GA) have proven to be
the best treatments with respect to the highest preservation of antioxidant
components. These treatments also exhibited higher antioxidant potential by DPPH
and β-carotene assays and noteworthy for an ABTS+ assays. Moreover, the
aforesaid treatments also demonstrated lower moisture content, aw, particle size
and higher solubility, hygroscopicity and glass transition temperature (Tg). All
freeze dried samples showed irregular (asymmetrical) microcrystalline structures.
Furthermore, TB and TC also illustrated the highest in vitro anti-diabetic
potential due to great potency for inhibiting α-amylase and α
glucosidase activities. In the perspective of bioavailability, TA, TB and TC
demonstrated the excellent bioavailability ratios (%). Furthermore, the
photochemical profiling of ethanolic extract of PHF was also revealed to find out
the bioactive compounds.
PMID- 29958446
TI - Square-Root Unscented Information Filter and Its Application in SINS/DVL
Integrated Navigation.
AB - To address the problem of low accuracy for the regular filter algorithm in
SINS/DVL integrated navigation, a square-root unscented information filter (SR
UIF) is presented in this paper. The proposed method: (1) adopts the state
probability approximation instead of the Taylor model linearization in EKF
algorithm to improve the accuracy of filtering estimation; (2) selects the most
suitable parameter form at each filtering stage to simply the calculation
complexity; (3) transforms the square root to ensure the symmetry and positive
definiteness of the covariance matrix or information matrix, and then to enhance
the stability of the filter. The simulation results indicate that the estimation
accuracy of SR-UIF is higher than that of EKF, and similar to UKF; meanwhile the
computational complexity of SR-UIF is lower than that of UKF.
PMID- 29958443
TI - Tick-Borne Encephalitis Virus: A Structural View.
AB - Tick-borne encephalitis virus (TBEV) is a growing health concern. It causes a
severe disease that can lead to permanent neurological complications or death and
the incidence of TBEV infections is constantly rising. Our understanding of
TBEV’s structure lags behind that of other flaviviruses, but has advanced
recently with the publication of a high-resolution structure of the TBEV virion.
The gaps in our knowledge include: aspects of receptor binding, replication and
virus assembly. Furthermore, TBEV has mostly been studied in mammalian systems,
even though the virus’ interaction with its tick hosts is a central part of
its life cycle. Elucidating these aspects of TBEV biology are crucial for the
development of TBEV antivirals, as well as the improvement of diagnostics. In
this review, we summarise the current structural knowledge on TBEV, bringing
attention to the current gaps in our understanding, and propose further research
that is needed to truly understand the structural-functional relationship of the
virus and its hosts.
PMID- 29958445
TI - Heterologous Production of Flavour and Aroma Compounds in Saccharomyces
cerevisiae.
AB - Over the last two decades, rapid progress in the field of synthetic biology has
opened several avenues for the heterologous de novo production of complex
biological compounds, such as biofuels, pharmaceuticals, and food additives in
microbial hosts. This minireview addresses the usage of the yeast Saccharomyces
cerevisiae as a microbial cell factory for the production of flavour and aroma
compounds, thereby providing a path towards a sustainable and efficient means of
producing what are normally rare, and often expensive plant-derived chemicals.
PMID- 29958447
TI - On-Line Learning of Write Strategy for Ultra-Speed CD-RW Optical Recorder.
AB - An on-line machine learning approach integrating the genetic algorithm (GA) and
jitter measurements is proposed to learn the write strategy for the infrared
diode of ultra-speed CD-RW recorders. The recording performance differs
significantly for the CD-RW discs recorded for the first, second, or third time
above. It is difficult to learn one set of write strategy parameters for the
infrared diode of ultra-speed CD-RW recorder that satisfies the recording
specifications for three different types of discs. The GA is applied to the on
line learning of write strategy. However, the convergence of GA stagnates at the
final stage of the learning process due to the fact that the write strategy
parameters learned by the GA need to satisfy the recording specifications for
discs recorded for the first time, second time and third time within one
recording trial. To overcome this difficulty, a scheme called dynamic parameter
encoding is proposed. This scheme improves the GA convergence and explores the
search space much better than the conventional GA.
PMID- 29958448
TI - Comparison of Tensile and Compressive Properties of Carbon/Glass Interlayer and
Intralayer Hybrid Composites.
AB - Tensile and compressive properties of interlayer and intralayer hybrid composites
were investigated in this paper. The tensile modulus and compression modulus of
interlayer and intralayer hybrid composites are the same under the same mixed
ratio, the tensile strength is much superior to the compression strength, and
while the tensile modulus and strength increase along with the carbon fiber
content, the compression values change slightly. The influence of stacking
structures on the tensile and compressive strengths is opposite to the ratio of
T/C (tensile/compression) strength for interlayer hybrid composites, and while
the tensile and compression strengths with glass fiber sandwiching carbon fiber
can reach the maximum value, the ratio of T/C strength is minimum. For structures
with carbon fiber sandwiching glass fiber, or with asymmetric structures, the
tensile and compressive strengths are at a low value. For intralayer hybrid
structures, while the carbon/glass (C/G) dispersion degree is high, the tensile
and compression strengths are low. The experimental tensile and compressive
strengths for interlayer and intralayer hybrid composites are greater than the
theoretical values, which demonstrates that strength conforms well to the
positive hybrid effect. The tensile fracture strain is greater than the
compression fracture strain for hybrid composites, with both of them basically
maintained at the same level.
PMID- 29958449
TI - Transcriptome-Wide Identification of an Aurone Glycosyltransferase with
Glycosidase Activity from Ornithogalum saundersiae.
AB - Aurone glycosides display a variety of biological activities. However, reports
about glycosyltransferases (GTs) responsible for aurones glycosylation are
limited. Here, the transcriptome-wide discovery and identification of an aurone
glycosyltransferase with glycosidase activity is reported. Specifically, a
complementary DNA (cDNA), designated as OsUGT1, was isolated from the plant
Ornithogalum saundersiae based on transcriptome mining. Conserved domain (CD)
search speculated OsUGT1 as a flavonoid GT. Phylogenetically, OsUGT1 is clustered
as the same phylogenetic group with a putative 5,6-dihydroxyindoline-2-carboxylic
acid (cyclo-DOPA) 5-O-glucosyltransferase, suggesting OsUGT1 may be an aurone
glycosyltransferase. The purified OsUGT1 was therefore used as a biocatalyst to
incubate with the representative aurone sulfuretin. In vitro enzymatic analyses
showed that OsUGT1 was able to catalyze sulfuretin to form corresponding
monoglycosides, suggesting OsUGT1 was indeed an aurone glycosyltransferase.
OsUGT1 was observed to be a flavonoid GT, specific for flavonoid substrates.
Moreover, OsUGT1 was demonstrated to display transglucosylation activity,
transferring glucosyl group to sulfuretin via o-Nitrophenyl-β-d
glucopyranoside (oNP-β-Glc)-dependent fashion. In addition, OsUGT1-catalyzed
hydrolysis was observed. This multifunctionality of OcUGT1 will broaden the
application of OcUGT1 in glycosylation of aurones and other flavonoids.
PMID- 29958450
TI - UAV Visual and Laser Sensors Fusion for Detection and Positioning in Industrial
Applications.
AB - This work presents a solution to localize Unmanned Autonomous Vehicles with
respect to pipes and other cylindrical elements found in inspection and
maintenance tasks both in industrial and civilian infrastructures. The proposed
system exploits the different features of vision and laser based sensors,
combining them to obtain accurate positioning of the robot with respect to the
cylindrical structures. A probabilistic (RANSAC-based) procedure is used to
segment possible cylinders found in the laser scans, and this is used as a seed
to accurately determine the robot position through a computer vision system. The
priors obtained from the laser scan registration help to solve the problem of
determining the apparent contour of the cylinders. In turn this apparent contour
is used in a degenerate quadratic conic estimation, enabling to visually estimate
the pose of the cylinder.
PMID- 29958451
TI - Synthesis of Honeycomb-Like Carbon Foam from Larch Sawdust as Efficient
Absorbents for Oil Spills Cleanup and Recovery.
AB - Hydrophobic oil absorbents with interconnected porous structure have been widely
used in dealing with the pervasive environmental issue of oil spills. In this
work, hydrophobic foams with 3D interconnected porous honeycomb structures of
liquefied-larch-based polymer foam (LLB-PF) and its carbonized product liquefied
larch-based carbon foam (LLB-CF) was prepared from larch sawdust waste and used
for oil and organics separation. The results revealed that the 3D interconnected
and open-cell honeycomb structure of LLB-PF was formed simultaneously during self
foaming, which remained intact even after carbonization. The two ultralight
foams, especially LLB-PF, exhibited remarkable oil/water selectivity. The foams
exhibited efficient and rapid absorption capacities, not only for oils but also
for organic solvents. LLB-PF and LLB-CF could absorb tetrachloromethane and
epoxidized soybean oil up to 88 and 153 times their own weight, respectively. The
recycle tests showed that LLB-PF and LLB-CF exhibited excellent absorption
capacities even after five cycles, demonstrating an excellent cyclability. The
high oil and organic solvent absorption performance along with the renewable and
low-cost starting materials positions LLB-PF and LLB-CF foams as promising
candidates with great potential for oil and organics cleanup.
PMID- 29958452
TI - Ultraviolet Detectors Based on Wide Bandgap Semiconductor Nanowire: A Review.
AB - Ultraviolet (UV) detectors have attracted considerable attention in the past
decade due to their extensive applications in the civil and military fields. Wide
bandgap semiconductor-based UV detectors can detect UV light effectively, and
nanowire structures can greatly improve the sensitivity of sensors with many
quantum effects. This review summarizes recent developments in the classification
and principles of UV detectors, i.e., photoconductive type, Schottky barrier
type, metal-semiconductor-metal (MSM) type, p-n junction type and p-i-n junction
type. The current state of the art in wide bandgap semiconductor materials
suitable for producing nanowires for use in UV detectors, i.e., metallic oxide,
III-nitride and SiC, during the last five years is also summarized. Finally,
novel types of UV detectors such as hybrid nanostructure detectors, self-powered
detectors and flexible detectors are introduced.
PMID- 29958453
TI - In Vitro and In Vivo Anti-Breast Cancer Activities of Some Synthesized
Pyrazolinyl-estran-17-one Candidates.
AB - A series of estrone derivatives, 2-4, were synthesized from the corresponding
arylidine estrone, 2a,b, as starting materials, which were prepared by
condensation of estrone (3-hydroxy-estran-17-one, 1) with 4-bromobenzaldehyde and
thiophene-2-aldehyde. Treating of 2a,b with hydrazine derivatives in acetic acid
or propionic acid afforded pyrazoline derivatives, 3a-f and 4a-f, respectively.
Furthermore, results proved the superiority of thienyl derivatives over 4
bromophenol derivatives in terms of cytotoxic effects on MCF-7 cancer cells. In
vivo xenograft breast cancer animal model experiments revealed that the
synthesized derivatives can be used for decreasing tumor volume, while the most
potent derivative (4f) decreased the development of tumor volume by about 87.0%
after 12 days.
PMID- 29958454
TI - Application and Extension of Vertical Intensity Lower-Mode in Methods for Target
Depth-Resolution with a Single-Vector Sensor.
AB - In this paper, based on the reactive component of the vertical intensity, the
method for target depth resolution has been improved. In the previous existing
research results, using the reactive component of vertical intensity, the
research objects for target depth resolution in shallow water, can only be the
targets whose frequencies can only excite the first two normal modes, and the
depth of targets whose frequencies excite more than two normal modes cannot be
correctly identified. The basic idea of the improved method is to classify
targets on the foundation of the lower-mode correlation quantity of the vertical
intensity. Based on the improved method, we can realize depth resolution of the
targets whose frequency can excite the first three normal modes so as to
effectively expand the working band useful for target depth resolution. Finally,
we can realize the three-dimensional target depth resolution so as to distinguish
the aerial, surface and underwater targets. The feasibility of the algorithm is
verified by simulation and experimental data processing.
PMID- 29958455
TI - Irisin Serum Levels in Metabolic Syndrome Patients Treated with Three Different
Diets: A Post-Hoc Analysis from a Randomized Controlled Clinical Trial.
AB - BACKGROUND: Irisin, a hormone-like myokine, regulates energy homeostasis and
mediates the benefits of physical activity on health. METHODS: To estimate the
effect of different diets on irisin concentrations in subjects with the Metabolic
Syndrome (MetS). METHODS: Subjects with MetS were derived from a population
survey; 163 subjects were enrolled and randomized to a: Low Glycaemic Index
(LGID), Mediterranean (MD) or Low Glycaemic Index Mediterranean (LGIMD) Diet, and
the groups were compared, also with 80 controls without MetS. Sociodemographic,
medical and nutritional data were collected and fasting blood samples drawn.
Subjects underwent LUS and bioimpedentiometry. Generalized Estimating Equations
were performed. RESULTS: At baseline, lower irisin concentrations were observed
in MetS subjects. Mean irisin levels increased in all diet groups but only the
LGID group reached statistical significance, as well as showing an interaction
between LGID and time at the sixth month examination (4.57, 95% CI −1.27,
7.87). There was a positive effect of Vegetable Proteins (0.03, 95% CI
−0.01,0.06) and Saturated Fatty Acids (0.04, 95% CI 0.01, 0.07) on irisin
concentrations. In the LGIMD, a positive effect on Fat-Free Mass (0.38, 95% CI
0.19, 0.57) and a negative effect on the Body Mass Index (−0.75, 95% CI
−1.30, −0.19) were observed. CONCLUSIONS: There seems to be a link
between diet and muscle physiology. We showed that patients following a LGID had
higher levels of irisin, a promising biomarker of muscle activity.
PMID- 29958456
TI - Simultaneous Determination and Pharmacokinetics of Peimine and Peiminine in
Beagle Dog Plasma by UPLC-MS/MS after the Oral Administration of Fritillariae
ussuriensis Maxim and Fritillariae thunbergii Miq Powder.
AB - A simple and high sensitive ultra-high performance liquid chromatography-tandem
mass spectrometry (UPLC-MS/MS) method was developed and validated for the
simultaneous determination of peimine and peiminine in beagle dog plasma after
the oral administration of Fritillariae ussuriensis Maxim and Fritillariae
thunbergii Miq powder. Chromatographic separation was achieved on an ACQUIT
UPLC® BEH C18 column (1.7 μm, 2.1 × 100 mm) in a gradient elution
way with a mobile phase consisting of acetonitrile and water containing 0.1%
formic acid at a flow rate of 0.4 mL/min. The plasma samples were prepared by a
liquid-liquid extraction (LLE) method with ethyl acetate. The analytes were
detected with a triple quadrupole tandem mass spectrometry (MS) in multiple
reaction monitoring (MRM) mode and a positive ion electrospray ionization (ESI)
of the transitions at m/z 432.4→414.4 for peimine and m/z 430.3→412.3
for peiminine. The method was linear for two analytes over the investigated range
with all determined correlation coefficients exceeding 0.9900. The lower limit of
quantification (LLOQ) was 0.988 ng/mL for peimine and 0.980 ng/mL for peiminine.
The mean extraction recoveries of peimine and peiminine at three quality control
samples (QC) levels were ranged from 82.56 to 88.71%, and matrix effects ranged
from 92.06 to 101.2%. The intra-day and inter-day precision and accuracy were
within the acceptable limits at LLOQ and QC levels. The method was effectively
and successfully applied to the pharmacokinetics of peimine and peiminine after
oral administration of powder to beagle dogs. The obtained results may be help to
guide the clinical application of Fritillaria ussuriensis Maxim and Fritillaria
thunbergii Miq.
PMID- 29958457
TI - A Review of Emotion Recognition Using Physiological Signals.
AB - Emotion recognition based on physiological signals has been a hot topic and
applied in many areas such as safe driving, health care and social security. In
this paper, we present a comprehensive review on physiological signal-based
emotion recognition, including emotion models, emotion elicitation methods, the
published emotional physiological datasets, features, classifiers, and the whole
framework for emotion recognition based on the physiological signals. A summary
and comparation among the recent studies has been conducted, which reveals the
current existing problems and the future work has been discussed.
PMID- 29958458
TI - The Vicious Circle of Working Hours, Sleep, and Recovery in Expert Work.
AB - This study aimed to investigate working hours, sleep quality and alertness, and
recovery and detachment in expert work using a mobile app. The study sample
comprised members of The Finnish Business School Graduates and employees of an
information technology (IT) company. The final study sample included 154
employees with at least four days of mobile app data. For statistical analyses of
the survey and mobile app data (cross-sectional setting), we used logistic
regression, and for the day-to-day data, we used multi-level logistic regression
to calculate the odds ratios (OR), and a general equation estimates model for
regression coefficients with 95% confidence intervals (CI). The results showed
that moderate to fair sleep quality or alertness at awakening were associated
with longer working hours the following day (OR 1.07-1.14, 95% CI 1.01-1.22).
Recovery and detachment during the preceding day were associated with longer
working hours. These associations were the same in the opposite direction. To
conclude, the day-to-day ratings of sleep quality and alertness at awakening, and
recovery and detachment from work during leisure time were associated with
increased working hours the following day. In addition, longer working hours the
preceding day were associated with worse ratings of sleep quality, alertness,
recovery, and detachment.
PMID- 29958459
TI - The Efficient Measurement of Job Satisfaction: Facet-Items versus Facet Scales.
AB - The measurement of job satisfaction as a central dimension for workplace health
and well-being is crucial to set suitable health- and performance-enhancing
management decisions. Measuring different facets of job satisfaction leads to a
more precise understanding about job satisfaction in research as well as to more
specific interventions in companies. This study examines the measurement of job
satisfaction with facet scales (multiple-items for one facet) and facet-items
(one item for one facet). Facet-items are a cost-effective and fast way to
measure job satisfaction in facets, whereas facet scales are more detailed and
provide further information. Results from 788 bank employees showed that facet
items of job satisfaction were significantly correlated with the corresponding
facet scales and had high factor loadings within the appropriate factor.
Furthermore, the same correlational pattern between facet scales and external
criteria was found for facet-items and external criteria (identification with the
company, work engagement, stress, resources). The findings support the usage of
facet-items in companies and in research where cost- and time-effectiveness is
imperative and the usage of facet scales where an even deeper understanding of
job satisfaction is needed. In practice, the usage of efficient measurements is
evident, especially in the upcoming field of eHealth tools.
PMID- 29958460
TI - DNA Injury and Repair Systems.
PMID- 29958461
TI - Differential Gene Expression Profile Induced by Valproic Acid (VPA) in Pediatric
Epileptic Patients.
AB - Epilepsy is a neuronal disease that affects up to 70 million people worldwide.
The development of effective therapies to combat childhood epilepsy requires
early biomarkers. Here, we performed a whole-genome microarray analysis in blood
cells to identify genes differentially expressed between epileptic and epileptic
valproic acid (VPA)-treated children versus normal children to obtain information
about the gene expression to help us to understand genetic aspects of this
disease. We found that the most significant differentially expressed genes were
related to the transcriptional factor cAMP-response element binding protein
(CREB) that is overexpressed in children with epilepsy compared with normal
children, and 6 and 12 months of VPA treatment reversed several of these changes.
Interestingly, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), a
type I transmembrane glycoprotein that binds collagen proteins and contains CREB
binding sites, was one of the more up-regulated genes in epileptic patients, and
treatment with VPA strongly reversed its up-regulation. CREB up-regulates genes
related to epilepsy; here, we suggest that LAIR1 could activate CREB, and
together, they trigger epilepsy. After VPA treatment, LAIR1 repressed genes by
disrupting the functional LAIR1-CREB complex, resulting in successful treatment.
A functional microarray analysis offers new information that could open novel
avenues of research in biomarker discovery, which may be useful for the early
identification of children with a predisposition to epilepsy.
PMID- 29958462
TI - Enhancing Received Signal Strength-Based Localization through Coverage Hole
Detection and Recovery.
AB - In wireless sensor networks (WSNs), Radio Signal Strength Indicator (RSSI)-based
localization techniques have been widely used in various applications, such as
intrusion detection, battlefield surveillance, and animal monitoring. One
fundamental performance measure in those applications is the sensing coverage of
WSNs. Insufficient coverage will significantly reduce the effectiveness of the
applications. However, most existing studies on coverage assume that the sensing
range of a sensor node is a disk, and the disk coverage model is too simplistic
for many localization techniques. Moreover, there are some localization
techniques of WSNs whose coverage model is non-disk, such as RSSI-based
localization techniques. In this paper, we focus on detecting and recovering
coverage holes of WSNs to enhance RSSI-based localization techniques whose
coverage model is an ellipse. We propose an algorithm inspired by Voronoi
tessellation and Delaunay triangulation to detect and recover coverage holes.
Simulation results show that our algorithm can recover all holes and can reach
any set coverage rate, up to 100% coverage.
PMID- 29958464
TI - Behavior and Mechanism of High-Temperature Stability between Tial-Based Alloy and
Y2O3-Al2O3 Composite Crucibles.
AB - In this work, Y2O3 based composite crucibles with different Al2O3 contents were
designed and characterized. The stability behaviors and interaction mechanisms
between molten Ti-47Al-2Cr-2Nb alloy and Y2O3-Al2O3 composite crucibles were
investigated at high temperature. Results showed that the surface morphology of
crucibles and the degree of interfacial reactions between the composite crucibles
and the metal melts varied with the change of Al2O3 content in the crucible
matrix. The pure Y2O3 crucible was the densest and its chemical stability was the
highest. With the increase in Al2O3 content, the number of pores on the crucibles
surface gradually increased and the interfacial reactions between the composite
crucibles and the molten alloys became weaker. When the content of Al2O3 in
composite crucibles increased from 3.5 wt % to 10.5 wt %, the thickness of the
interface layer of melt-crucible decreased from 150 µm to 50 µm, and
the equilibrium contact angles between metal and crucibles gradually decreased
from 69.3° to 64.2° at 1873 K.
PMID- 29958463
TI - Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High
Density Lipoproteins.
AB - Angiogenesis, the process of forming new blood vessels, is crucial in the
physiological response to ischemia, though it can be detrimental as part of
inflammation and tumorigenesis. We have previously shown that high-density
lipoproteins (HDL) modulate angiogenesis in a context-specific manner via
distinct classical signalling pathways, enhancing hypoxia-induced angiogenesis
while suppressing inflammatory-driven angiogenesis. Whether additional novel
targets exist to account for these effects are unknown. A microarray approach
identified two novel genes, cyclic-adenosine-monophosphate-response-element
binding protein 3 regulatory factor (CREBRF) and tripartite motif-containing
protein 2 (TRIM2) that were upregulated by reconstituted HDL (rHDL). We measured
CREBRF and TRIM2 expression in human coronary artery endothelial cells following
incubation with rHDL and exposure to either hypoxia or an inflammatory stimulus.
We found that CREBRF and TRIM2 mRNA were significantly upregulated by rHDL,
particularly in response to its phospholipid component 1-palmitoyl-2-linoleoyl
phosphatidylcholine, however, protein expression was not significantly altered.
Knockdown of TRIM2 impaired endothelial cell tubulogenesis in vitro in both
hypoxia and inflammation, implying a necessary role in angiogenesis. Furthermore,
TRIM2 knockdown attenuated rHDL-induced tubule formation in hypoxia, suggesting
that it is important in mediating the pro-angiogenic action of rHDL. Our study
has implications for understanding the regulation of angiogenesis in both of
these pathophysiological contexts by HDL.
PMID- 29958465
TI - Multifunction RF Systems for Naval Platforms.
AB - The evolving role of modern navies has required increasingly higher levels of
capability in the Radio Frequency (RF) shipboard systems that provide radar,
communications, Electronic Attack (EA) and Electronic Support (ES) functions. The
result has been a proliferation of topside antennas and associated hardware on
naval vessels. The notion of MultiFunction RF (MFRF) systems has drawn
considerable interest as an approach to reversing this trend. In a MFRF system,
RF functions are consolidated within a shared set of electronics and antenna
apertures that utilize Active Electronically Scanned Array (AESA) technology.
This paper highlights a number of issues to be considered in the design and
implementation of a naval MFRF system. Specifically, the key requirements of the
RF functions of interest are first reviewed, and MFRF system design trade-offs
resulting from costs and/or performance limitations in existing hardware
technology are then discussed. It is found that limitations in hardware
technology constrain the implementation of practical MFRF systems. MFRF system
prototype development programs that have been conducted in other countries are
described. MFRF resource allocation management is identified as an important
future research topic.
PMID- 29958466
TI - Use of Sorption of Copper Cations by Clinoptilolite for Wastewater Treatment.
AB - This paper from the field of environmental chemistry offers an innovative use of
sorbents in the treatment of waste industrial water. Various industrial
activities, especially the use of technological fluids in machining, surface
treatment of materials, ore extraction, pesticide use in agriculture, etc.,
create wastewater containing dangerous metals that cause serious health problems.
This paper presents the results of studies of the natural zeolite clinoptilolite
as a sorbent of copper cations. These results provide the measurement of the
sorption kinetics as well as the observed parameters of sorption of copper
cations from the aquatic environment to the clinoptilolite from a promising
Slovak site. The effectiveness of the natural sorbent is also compared with that
of certain known synthetic sorbents.
PMID- 29958467
TI - Potential of Visible and Near-Infrared Hyperspectral Imaging for Detection of
Diaphania pyloalis Larvae and Damage on Mulberry Leaves.
AB - Mulberry trees are an important crop for sericulture. Pests can affect the yield
and quality of mulberry leaves. This study aims to develop a hyperspectral
imaging system in visible and near-infrared (NIR) region (400-1700 nm) for the
rapid identification of Diaphania pyloalis larvae and its damage. The extracted
spectra of five region of interests (ROI), namely leaf vein, healthy mesophyll,
slight damage, serious damage, and Diaphania pyloalis larva at 400-1000 nm
(visible range) and 900-1700 nm (NIR range), were used to establish a partial
least squares discriminant analysis (PLS-DA) and least-squares support vector
machines (LS-SVM) models. Successive projections algorithm (SPA), uninformation
variable elimination (UVE), UVE-SPA, and competitive adaptive reweighted sampling
were used for variable selection. The best models in distinguishing between leaf
vein, healthy mesophyll, slight damage and serious damage, leaf vein, healthy
mesophyll, and larva, slight damage, serious damage, and larva were all the SPA
LS-SVM models, based on the NIR range data, and their correct rate of prediction
(CRP) were all 100.00%. The best model for the identification of all five ROIs
was the UVE-SPA-LS-SVM model, based on visible range data, which had the CRP
value of 97.30%. In summary, visible and near infrared hyperspectral imaging
could distinguish Diaphania pyloalis larvae and their damage from leaf vein and
healthy mesophyll in a rapid and non-destructive way.
PMID- 29958468
TI - Synthesis and Characterization of Hollow Mesoporous Silica Nanoparticles for
Smart Corrosion Protection.
AB - Different approaches have been considered for the development of smart
anticorrosive coatings by the incorporation of nanocontainers loaded with
corrosion inhibitors into the protective layer. Nanocontainers are designed to
allow a controlled release of the inhibitor in response to an external stimulus,
thus, achieving more efficient and more economical use of the active component.
In this case, a pH change is a very interesting stimulus to trigger the release
because corrosion processes cause local pH changes. To this end, a special focus
has been placed on the use of mesoporous silica nanoparticles (MSN) as
nanocontainers due to their interesting characteristics, such as larger surface
area, versatile functionalisation, stability, etc. However, the use of hollow
mesoporous silica nanoparticles (HMSN), with a large central hole combined with
an external mesoporous silica shell, offers an additional advantage due to the
higher loading capacity. In the present work, HMSN have been efficiently
synthesised, loaded with sodium phosphomolybdate, as a non-toxic alternative to
the use of chromates, and encapsulated by a layer of an oppositely charged
polyelectrolyte, poly(diallyldimethylammonium chloride) (PDDA). The morphology
and textural properties of the produced nanocapsules have been studied by
different techniques (SEM/EDS, TEM/EDS, Brunauer-Emmett-Teller (BET) analysis
method, ζ-potential). Finally, the releasing capacity and corrosion
protection at different pH values have been studied, confirming the smart
behaviour of the encapsulated loaded HMSN.
PMID- 29958469
TI - Walking and Walkability in Pre-Set and Self-Defined Neighborhoods: A Mental
Mapping Study in Older Adults.
AB - Neighborhood walkability contributes to older adults’ walking. However,
associations vary depending on the neighborhood definition applied as well as
between objective and perceived walkability measures. Therefore, this study aimed
to comparatively assess walkability indices for commonly used pedestrian network
buffers and perceived neighborhood areas. A total of 97 adults aged ≥65 years
answered a written physical activity questionnaire and 69 respondents
participated in face-to-face interviews that involved mental mapping, i.e., to
draw perceived neighborhood delineations on paper maps. Hierarchical regression
analyses were used to compare the contribution of walkability indices for pre-set
buffers and self-defined neighborhoods to older adults’ walking after
adjusting for covariates. Results show that older adults’ self-defined
neighborhoods are significantly larger, less home-centered, and more walkable
than commonly used buffers. Furthermore, the variance accounted for in
neighborhood walking increased from 35.9% to 40.4% (ΔR2 = 0.046; p =
0.029), when the walkability index was calculated for self-defined neighborhoods
rather than pre-set buffers. Therefore, the study supports that geometric
differences between pre-set buffers and older adults’ spatial ideas of
perceived neighborhoods have a significant influence on estimated walkability
effects and that exposure areas should be matched with the spatial dimension of
outcome variables in future research.
PMID- 29958470
TI - On the Development of Health-Based Ventilation Guidelines: Principles and
Framework.
AB - This paper summarizes the results of HealthVent project. It had an aim to develop
health-based ventilation guidelines and through this process contribute to
advance indoor air quality (IAQ) policies and guidelines. A framework that allows
determining ventilation requirements in public and residential buildings based on
the health requirements is proposed. The framework is based on three principles:
1. Criteria for permissible concentrations of specific air pollutants set by
health authorities have to be respected; 2. Ventilation must be preceded by
source control strategies that have been duly adopted to improve IAQ; 3. Base
ventilation must always be secured to remove occupant emissions (bio-effluents).
The air quality guidelines defined by the World Health Organization (WHO) outside
air are used as the reference for determining permissible levels of the indoor
air pollutants based on the principle that there is only one air. It is proposed
that base ventilation should be set at 4 L/s per person; higher rates are to be
used only if WHO guidelines are not followed. Implementation of the framework
requires technical guidelines, directives and other legislation. Studies are also
needed to examine the effectiveness of the approach and to validate its use. It
is estimated that implementing the framework would bring considerable reduction
in the burden of disease associated with inadequate IAQ.
PMID- 29958471
TI - STVF: Spatial-Temporal Variational Filtering for Localization in Underwater
Acoustic Sensor Networks.
AB - Localization is one of the critical services in Underwater Acoustic Sensor
Networks (UASNs). Due to harsh underwater environments, the nodes often move with
currents continuously. Consequently, the acoustic signals usually propagate with
varying speeds in non-straight lines and the noise levels change frequently with
the motion of the nodes. These limitations pose huge challenges for localization
in UASNs. In this paper, we propose a novel localization method based on a
variational filtering technique, in which the spatial correlation and temporal
dependency information are utilized to improve localization performance. In the
method, a state evolution model is employed to characterize the mobility pattern
of the nodes and capture the uncertainty of the location transition. Then, a
measurement model is used to reflect the relation between the measurements and
the locations considering the dynamics of the acoustic speed and range noise.
After that, a variational filtering scheme is adopted to determine the
nodes’ locations, which consists of two phases: variational prediction and
update. In the former phase, the coarse estimation of each node’ location
is computed based on its previous location; in the latter phase, the coarse
location is optimized by incorporating the measurements from the reference nodes
as precisely as possible. At last, an iterative localization scheme is applied,
in which a node labels itself as a reference node if the confidence of its
location estimation is higher than the predefined threshold. We conducted
extensive simulations under different parameter settings, and the results
indicate that the proposed method has better localization accuracy compared to a
typical SLMP algorithm while maintaining relatively high localization coverage.
Moreover, spatial-temporal variational filtering (STVF) is more robust to the
change of the parameter settings compared to SLMP.
PMID- 29958472
TI - A Novel HPLC Method for Direct Detection of Nitric Oxide Scavengers from Complex
Plant Matrices and Its Application to Aloysia triphylla Leaves.
AB - The present study aimed at developing an original pre-column HPLC assay allowing
rapid characterization of nitric oxide (NO) scavengers from complex plant
extracts. Sodium nitroprusside (SNP) was employed as a NO donor and spiked with
an aqueous extract from Aloysia triphylla leaves prior to HPLC analysis. Relying
on the ability of radical scavenging constituents to be oxidized upon reaction
with radicals, this assay successfully allowed direct identification of three
potential NO scavengers, including verbascoside, isoverbascoside, and luteolin-7
O-diglucuronide. These three phenolics were also individually assessed for their
NO scavenging activities by using a Griess colorimetric assay. With respective
IC50 values of 56 +/- 4, 51 +/- 3, and 69 +/- 5 µg/mL, verbascoside,
isoverbascoside, and luteolin-7-O-diglucuronide were all reported as potent NO
scavenging compounds, confirming the efficiency of the SNP spiking HPLC assay.
The present method can, thus, be considered as a valuable and effective approach
for speeding up the discovery of NO scavenging constituents.
PMID- 29958474
TI - Design and Test of a New Inductive Force Sensor.
AB - The currently accepted interval of weekly cast changes in the treatment of
clubfeet seems unsubstantiated. A force sensor is needed to determine the
adaptation rate of a clubfoot to establish what cast change interval would be
most effective and efficient. We developed a force sensor based on the principle
that the resonance frequency of an LC-tank changes when a metal target is brought
in close proximity. A thin rubber ring between the LC-tank and the metal target
transformed this proximity sensor into a force sensor. With a static load test
and an incremental load test, the performance of the constructed force sensors
was characterized. The custom-made sensor showed excellent sensitivity ((1.7+/
0.8×105) counts/N), resolution ((0.15+/-0.06) mN), and accuracy ((3.5+/
3.0) %) for the application. The observed drift was (2.1+/-0.7) %/log10(h), which
is lower than other thin force sensors. Preliminary results of measurements in
the treatment of Dupuytren fingers and clubfeet show good functioning for long
term force measurements.
PMID- 29958473
TI - GW2 Functions as an E3 Ubiquitin Ligase for Rice Expansin-Like 1.
AB - Seed size is one of the most important traits determining the yield of cereal
crops. Many studies have been performed to uncover the mechanism of seed
development. However, much remains to be understood, especially at the molecular
level, although several genes involved in seed size have been identified. Here,
we show that rice Grain Width 2 (GW2), a RING-type E3 ubiquitin ligase, can
control seed development by catalyzing the ubiquitination of expansin-like 1
(EXPLA1), a cell wall-loosening protein that increases cell growth. Microscopic
examination revealed that a GW2 mutant had a chalky endosperm due to the presence
of loosely packed, spherical starch granules, although the grain shape was
normal. Yeast two-hybrid and in vitro pull-down assays showed a strong
interaction between GW2 and EXPLA1. In vitro ubiquitination analysis demonstrated
that EXPLA1 was ubiquitinated by GW2 at lysine 279 (K279). GW2 and EXPLA1
colocalized to the nucleus when expressed simultaneously. These results suggest
that GW2 negatively regulates seed size by targeting EXPLA1 for degradation
through its E3 ubiquitin ligase activity.
PMID- 29958475
TI - Green Fluorescent Protein-Based Viability Assay in a Multiparametric
Configuration.
AB - Green fluorescent protein (GFP) is considered to be suitable for cell viability
testing. In our study, GFP transfected A549 lung carcinoma cell line was treated
with sodium fluoride (NaF), cycloheximide (CHX) and ochratoxin A (OTA). GFP
fluorescence, intracellular ATP, nucleic acid and protein contents were
quantified by a luminescence microplate assay developed in our laboratory. Flow
cytometry was used to confirm the findings and to assess the intensity of GFP
during different types of cell death. A 24 h NaF and CHX exposure caused a
dramatic decrease in ATP contents (p < 0.05) compared with those of the controls.
GFP fluorescence of the cells was in close correlation with total protein;
however, GFP/ATP increased at NaF and decreased at CHX treatments (p < 0.05).
ATP/protein and ATP/propidium iodide (PI) were largely decreased at NaF exposure
in a dose-dependent manner (p < 0.05), while CHX and OTA showed markedly fewer
effects. Both treatments caused apoptosis/necrosis at different rates. NaF
induced mainly late apoptosis while OTA, mainly apoptosis. CHX effects varied by
the incubation time with 100-fold elevation in late apoptotic cells at 24 h
treatment. GFP intensity did not show a significant difference between live and
apoptotic populations. Our results suggest when using GFP, a multiparametric
assay is necessary for more precise interpretation of cell viability.
PMID- 29958476
TI - Concentration of Immunoglobulins in Microfiltration Permeates of Skim Milk:
Impact of Transmembrane Pressure and Temperature on the IgG Transmission Using
Different Ceramic Membrane Types and Pore Sizes.
AB - The use of bioactive bovine milk immunoglobulins (Ig) has been found to be an
alternative treatment for certain human gastrointestinal diseases. Some
methodologies have been developed with bovine colostrum. These are considered in
laboratory scale and are bound to high cost and limited availability of the raw
material. The main challenge remains in obtaining high amounts of active IgG from
an available source as mature cow milk by the means of industrial processes.
Microfiltration (MF) was chosen as a process variant, which enables a gentle and
effective concentration of the Ig fractions (ca. 0.06% in raw milk) while
reducing casein and lactose at the same time. Different microfiltration membranes
(ceramic standard and gradient), pore sizes (0.14-0.8 µm), transmembrane
pressures (0.5-2.5 bar), and temperatures (10, 50 °C) were investigated. The
transmission of immunoglobulin G (IgG) and casein during the filtration of raw
skim milk (<0.1% fat) was evaluated during batch filtration using a single
channel pilot plant. The transmission levels of IgG (~160 kDa) were measured to
be at the same level as the reference major whey protein β-Lg (~18 kDa) at
all evaluated pore sizes and process parameters despite the large difference in
molecular mass of both fractions. Ceramic gradient membranes with a pore sizes of
0.14 µm showed IgG-transmission rates between 45% to 65% while reducing the
casein fraction below 1% in the permeates. Contrary to the expectations, a lower
pore size of 0.14 µm yielded fluxes up to 35% higher than 0.2 µm MF
membranes. It was found that low transmembrane pressures benefit the Ig
transmission. Upscaling the presented results to a continuous MF membrane process
offers new possibilities for the production of immunoglobulin enriched
supplements with well-known processing equipment for large scale milk protein
fractionation.
PMID- 29958478
TI - Robust Face Recognition Using the Deep C2D-CNN Model Based on Decision-Level
Fusion.
AB - Given that facial features contain a wide range of identification information and
cannot be completely represented by a single feature, the fusion of multiple
features is particularly significant for achieving a robust face recognition
performance, especially when there is a big difference between the test sets and
the training sets. This has been proven in both traditional and deep learning
approaches. In this work, we proposed a novel method named C2D-CNN (color 2
dimensional principal component analysis (2DPCA)-convolutional neural network).
C2D-CNN combines the features learnt from the original pixels with the image
representation learnt by CNN, and then makes decision-level fusion, which can
significantly improve the performance of face recognition. Furthermore, a new CNN
model is proposed: firstly, we introduce a normalization layer in CNN to speed up
the network convergence and shorten the training time. Secondly, the layered
activation function is introduced to make the activation function adaptive to the
normalized data. Finally, probabilistic max-pooling is applied so that the
feature information is preserved to the maximum extent while maintaining feature
invariance. Experimental results show that compared with the state-of-the-art
method, our method shows better performance and solves low recognition accuracy
caused by the difference between test and training datasets.
PMID- 29958480
TI - An Optimization-Based Initial Alignment and Calibration Algorithm of Land-Vehicle
SINS In-Motion.
AB - For a running freely land-vehicle strapdown inertial navigation system (SINS),
the problems of self-calibration and attitude alignment need to be solved
simultaneously. This paper proposes a complete alignment algorithm for the land
vehicle navigation using Inertial Measurement Units (IMUs) and an odometer. A
self-calibration algorithm is proposed based on the global observability analysis
to calibrate the odometer scale factor and IMU misalignment angle, and the
initial alignment and calibration method based on optimal algorithm is
established to estimate the attitude and other system parameters. This new
algorithm has the capability of self-initialization and calibration without any
prior attitude and sensor noise information. Computer simulation results show
that the performance of the proposed algorithm is superior to the extended Kalman
filter (EKF) method during the oscillating attitude motions, and the vehicle test
validates its advantages.
PMID- 29958479
TI - DNA Interaction with Head-to-Tail Associates of Cationic Surfactants Prevents
Formation of Compact Particles.
AB - Cationic azobenzene-containing surfactants are capable of condensing DNA in
solution with formation of nanosized particles that can be employed in gene
delivery. The ratio of surfactant/DNA concentration and solution ionic strength
determines the result of DNA-surfactant interaction: Complexes with a micelle
like surfactant associates on DNA, which induces DNA shrinkage, DNA precipitation
or DNA condensation with the emergence of nanosized particles. UV and
fluorescence spectroscopy, low gradient viscometry and flow birefringence methods
were employed to investigate DNA-surfactant and surfactant-surfactant interaction
at different NaCl concentrations, [NaCl]. It was observed that [NaCl] (or the
Debye screening radius) determines the surfactant-surfactant interaction in
solutions without DNA. Monomers, micelles and non-micellar associates of
azobenzene-containing surfactants with head-to-tail orientation of molecules were
distinguished due to the features of their absorption spectra. The novel data
enabled us to conclude that exactly the type of associates (together with the
concentration of components) determines the result of DNA-surfactant interaction.
Predomination of head-to-tail associates at 0.01 M < [NaCl] < 0.5 M induces DNA
aggregation and in some cases DNA precipitation. High NaCl concentration (higher
than 0.8 M) prevents electrostatic attraction of surfactants to DNA phosphates
for complex formation. DAPI dye luminescence in solutions with DNA-surfactant
complexes shows that surfactant tails overlap the DNA minor groove. The addition
of di- and trivalent metal ions before and after the surfactant binding to DNA
indicate that the bound surfactant molecules are located on DNA in islets.
PMID- 29958481
TI - Recent Surface Water Extent of Lake Chad from Multispectral Sensors and GRACE.
AB - Consistent observations of lakes and reservoirs that comprise the majority of
surface freshwater globally are limited, especially in Africa where water bodies
are exposed to unfavorable climatic conditions and human interactions. Publicly
available satellite imagery has increased the ability to monitor water bodies of
various sizes without much financial hassle. Landsat 7 and 8 images were used in
this study to estimate area changes around Lake Chad. The Automated Water
Extraction Index (AWEI), Normalized Difference Water Index (NDWI), Modified
Normalized Difference Water Index (MNDWI) and Normalized Difference Vegetation
Index (NDVI) were compared for the remote sensing retrieval process of surface
water. Otsu threshold method was used to separate water from non-water features.
With an overall accuracy of ~96% and an inter-rater agreement (kappa coefficient)
of 0.91, the MNDWI was a better indicator for mapping recent area changes in Lake
Chad and was used to estimate the lake’s area changes from 2003-2016.
Extracted monthly areas showed an increasing trend and ranged between ~1242 km2
and 2231 km2 indicating high variability within the 13-year period, 2003-2016. In
addition, we combined Landsat measurements with Total Water Storage Anomaly
(TWSA) data from the Gravity Recovery and Climate Experiment (GRACE) satellites.
This combination is well matched with our estimated surface area trends. This
work not only demonstrates the importance of remote sensing in sparsely gauged
developing countries, it also suggests the use of freely available high-quality
imagery data to address existing lake crisis.
PMID- 29958483
TI - Ultrastructural evidence of extruding exocytosis of residual bodies in the
freshwater sponge Ephydatia fluviatilis.
AB - Exocytosis of residual bodies by choanocytes, archeocytes and endopinacocytes
lining the aquiferous system of Ephydatia fluviatilis has been demonstrated using
calibrated latex beads and Escherichia coli as tracers. In passing into the
mesohyl or the lumen of the exhalant aquiferous canals, beads, and altered
bacteria were enveloped by the plasma membrane of the cell containing them. The
membrane constricted at a neck region to form extruding vacuoles. This process
appeared first in choanocytes and later in other cell types. The occurrence of
these buds increased with the length of incubation time, as did the number of
particles they contained. Acid phosphatase activity was frequently associated
with the particles budding from the cell membrane, confirming that this process
followed digestive activity. Membranous vacuoles were recovered from the external
medium and observed by TEM and those adhering to the substratum were seen by SEM.
These observations proved that vacuoles were released from the sponges. This
membrane-consuming mechanism of exoctyosis implies intense membrane replacement
in the digestive cells of the sponge.
PMID- 29958477
TI - Above the Epitranscriptome: RNA Modifications and Stem Cell Identity.
AB - Sequence databases and transcriptome-wide mapping have revealed different
reversible and dynamic chemical modifications of the nitrogen bases of RNA
molecules. Modifications occur in coding RNAs and noncoding-RNAs post
transcriptionally and they can influence the RNA structure, metabolism, and
function. The result is the expansion of the variety of the transcriptome. In
fact, depending on the type of modification, RNA molecules enter into a specific
program exerting the role of the player or/and the target in biological and
pathological processes. Many research groups are exploring the role of RNA
modifications (alias epitranscriptome) in cell proliferation, survival, and in
more specialized activities. More recently, the role of RNA modifications has
been also explored in stem cell biology. Our understanding in this context is
still in its infancy. Available evidence addresses the role of RNA modifications
in self-renewal, commitment, and differentiation processes of stem cells. In this
review, we will focus on five epitranscriptomic marks: N6-methyladenosine, N1
methyladenosine, 5-methylcytosine, Pseudouridine (Ψ) and Adenosine-to-Inosine
editing. We will provide insights into the function and the distribution of these
chemical modifications in coding RNAs and noncoding-RNAs. Mainly, we will
emphasize the role of epitranscriptomic mechanisms in the biology of naïve,
primed, embryonic, adult, and cancer stem cells.
PMID- 29958484
TI - Ultrastructure and function of the circulatory organs of Leiobunum limbatum and
two other species of harvestmen (arachnida: Opiliones).
AB - The ultrastructure of the circulatory organs of Leiobunum limbatum, Mitopus
morio, and Rilaena triangularis (Arachnida: Opiliones) has been investigated. We
studied the organization of the heart, the myocardial contractile elements, its
tubular system, organelles, and cell-junctions. The epicardium exhibits a large
number of longitudinally arranged microtubules and is attached to the myocardium
by special membrane complexes. Because of these structures, the epicardium is
interpreted as the elastic antagonist to the heart muscle. At both ends of the
heart the epicardium continues into a nonbranching aorta. Consequently the
ultrastructure of the aortal wall, containing numerous microtubules, is similar
to the ultrastructure of the epicardium. At the posterior end of the heart is a
muscular slit-valve, while at the anterior end is a lobe-valve that lacks
contractile elements. The heart is innervated by a dorsal ganglion. It covers the
entire length of the heart and contains neural and glial cells. Two different
types of neurosecretory granules and both electron-dense and electron-lucent
synaptic vesicles are described.
PMID- 29958482
TI - Proximal Optical Sensors for Nitrogen Management of Vegetable Crops: A Review.
AB - Optimal nitrogen (N) management is essential for profitable vegetable crop
production and to minimize N losses to the environment that are a consequence of
an excessive N supply. Proximal optical sensors placed in contact with or close
to the crop can provide a rapid assessment of a crop N status. Three types of
proximal optical sensors (chlorophyll meters, canopy reflectance sensors, and
fluorescence-based flavonols meters) for monitoring the crop N status of
vegetable crops are reviewed, addressing practical caveats and sampling
considerations and evaluating the practical use of these sensors for crop N
management. Research over recent decades has shown strong relationships between
optical sensor measurements, and different measures of crop N status and of yield
of vegetable species. However, the availability of both: (a) Sufficiency values
to assess crop N status and (b) algorithms to translate sensor measurements into
N fertilizer recommendations are limited for vegetable crops. Optical sensors
have potential for N management of vegetable crops. However, research should go
beyond merely diagnosing crop N status. Research should now focus on the
determination of practical fertilization recommendations. It is envisaged that
the increasing environmental and societal pressure on sustainable crop N
management will stimulate progress in this area.
PMID- 29958485
TI - The sphincter of the efferent filament artery in teleost gills: I. Structure and
parasympathetic innervation.
AB - Previous studies have shown the existence of a sphincter in the efferent filament
artery of the teleost gill and its constrictory response to acetylcholine (ACH)
and vagal stimulation. This study deals with the muscular organization of this
sphincter and the distribution of its innervation as elucidated by degeneration
methods and cytochemistry. The sphincter innervation is supplied by the
protrematic vagus nerves. Nerve endings filled with cholinergic-type vesicles are
located in close association with the adventitial smooth muscle cells and display
a strong acetylcholinesterase (ACHE) activity. Section of the protrematic vagus
nerve induces a nearly complete degeneration of the sphincter innervation. ACHE
positive nerve cell bodies are present both in the sphincter area and in the
protrematic vagus nerve. These results suggest that innervation of the sphincter
in the efferent filament artery is cholinergic through the activity of
postganglionic axons of the parasympathetic system.
PMID- 29958486
TI - Ultrastructural aspects of the surface coatings of eggs and larvae of the
starfish, Pisaster ochraceus, revealed by alcian blue.
AB - Eggs of the asteroid Pisaster ochraceus demonstrate cortical granules, a thick
vitelline membrane, and a poorly stained jelly coat similar to that seen on the
eggs of other echinoderms. When fixed in the presence of alcian blue the jelly
coat is seen to be made up of three regions, an inner layer consisting of a
meshwork of fibres, a middle layer of thicker fibres, and a dense outer layer. At
fertilization the cortical granules release their contents into the potential
space between the vitelline layers and a low fertilization membrane consisting of
the vitelline layer and a dense component of the corticle granule is formed.
Initially the remaining contents of the corticle granules form an amorphous
hyaline layer that fills the space between the plasma membrane and the
fertilization membrane. At hatching a distinct hyaline layer is present. It
persists at least to the bipinnaria stage and consists of four distinct layers. A
similar layer is also located over much of the early embryonic endoderm but is
lost from the regions involved in the formation of the mesenchyme cells, coelom,
and mouth just before these events take place. Numerous large clear vesicles are
located in the apex of all cells associated with a hyaline layer. Where the
hyaline layer is lacking, only scattered vesicles are present suggesting that the
vesicles may be involved in maintenance of the layer. Attempts to identify
elements of the hyaline layer by immunofluorescence demonstrated that it appears
to bind both antisera and control sera in a nonspecific manner.
PMID- 29958487
TI - The ultrastructure of the morula cells of Eupentacta quinquesemita
(Echinodermata: Holothuroidea) and their role in the maintenance of the
extracellular matrix.
AB - The ultrastructure of the morula cells of Eupentacta quinquesemita and the
distribution of these cells in the dermal connective tissue are described. Morula
cells are abundant in the dermis and appear to function in the maintenance of the
extracellular matrix (ECM) as a source of ground substance material. The
synthetic activity of these cells is described in detail. Morula cells are filled
with large secretory vesicles containing three electrondense materials which are
derived from rough endoplasmic reticulum and Golgi activity. The synthetic
product of these cells contains glycosaminoglycans and is secreted into the ECM
by degranulation. The ultrastructural and histochemical similarity of the
degranulation product to the ECM ground substance suggests that they are
comprised of the same material. Morula cells appear to function primarily in
connective tissues where ground substance predominates. The cells often contain
secretory vesicles at various stages of formation, all of which eventually mature
and degranulate. The synthetic pathway of the morula cells appears to result
ultimately in the complete disruption and death of the cells. The function of
morula cells in the holothuroid ECM is discussed, and the synthetic activity of
the cells is compared with that of other secretory cells.
PMID- 29958488
TI - Ultrastructural aspects of mouth formation in the starfish Pisaster ochraceus.
AB - Early events during mouth formation in embryos of the starfish Pisaster ochraceus
have been studied with scanning electron microscopy (SEM) and transmission
electron microscopy (TEM). Embryos examined by TEM were fixed in glutaraldehyde
with Alcian blue, a dye which preserves extracellular materials. Initially,
mesenchyme cells migrate off the tip of the archenteron, leaving a defect in the
cell layer that is covered by the basal lamina. This region of "naked" basal
lamina bulges into the blastocoele and forms a hemispherical blister. At the same
time that this is occurring, filamentous and conical processes extend from the
inner surface of the presumptive stomodeal ectoderm cells which are located
directly opposite the bulge of basal lamina. These processes penetrate the
ectodermal basal lamina and project "naked" plasmalemma into the blastocoele.
Shortly after this, the blister of endodermal basal lamina becomes irregular in
shape, and scattered cells are found both within the blister and between it and
the presumptive stomodeal ectoderm cells. Processes of endodermal cells appear to
make contact with the filamentous processes of the stomodeal ectoderm cells. In
other embryos which appear to be at a slightly later stage, the free basal lamina
is conical in shape and is associated with at least one conical ectodermal
process. In yet other embryos, the free endodermal basal lamina is either in
contact with several other large processes forming a circular region of contact,
or the free endodermal and ectodermal basal laminae are fused at the edge of the
circle. Degeneration of both the ectodermal and endodermal basal laminae located
within the circle, and subsequent invagination of the stomodeal ectoderm, appear
to complete this process. The pulsations of stomodeal ectodermal cells seen
throughout early stages in mouth formation may be involved in these events.
PMID- 29958489
TI - Tympanohyal bone in toothed whales and the formation of the tympano-periotic
complex (Mammalia: Cetacea).
AB - A tympanohyal bone is reported in dolphins for the first time. The exceptional
occurrence of this element in the bottlenose dolphin (Tursiops truncatus) and its
location in a furrow of the tympanic can be taken as a vestige of an ancestral
conformation indicating that, in cetacean ancestry, uncoupling of the periotic
from the mastoid must have taken place laterally and dorsally to attachment of
the hyoid arch and the stylomastoid foramen. There is a good correspondence
between morphology and topographical relations of structures surrounding the
facial canal in toothed whales and terres-trial mammals (especially
perissodactyls and artiodactyls). During early cetacean evolution, the tympanic
had to undergo strong modification because of its functional correlation with the
periotic. In precetaceans, the tympanic was probably loosely attached to
neighboring skull bones, while at the same time it was suspended from the
periotic via the tympanohyal. The earliest known cetaceans obviously lost this
indirect osseous suspension but retained the peripheral attachments of the
tympanic. In advanced archeocetes, two of these attachments are maintained but
have shifted onto the periotic. In modern dolphins, the tympanic is in firm
osseous contact exclusively with the periotic (tympano-periotic complex). Both
elements are isolated from the skull acoustically and form a separate mechanical
unit specialized for high-frequency underwater sound perception.
PMID- 29958490
TI - The vacuolar cells of Oscarella lobularis (Porifera, Demospongiae):
Ulatrastructural organization, origin, and function.
AB - This work is concerned with the ultrastructural organization and some
histochemical features of the vacuolar cells of the demosponge Oscarella
lobularis. Vacuolar cells are characterized by large clear vacuoles containing an
aqueous fluid. They are commonly found in the mesohyl of this sponge and tend to
constitute a sort of parenchyma in the choanosome. Mobile cells of the mesohyl
appear to differetiate into vacuolar cells through the progressive formation of
wide cytoplasmic lacunae. We have identified four types of cells showing
progressive transformation toward the vacuolar cell type. Precursors (types 1-4)
of the vacuolar cells probably derive from endopinacocytes, since they share
several histochemical and ultrastructural characteristics with them. Our data
support the notion that vacuolar cells are involved in the synthesis of collagen,
act as a mechanical support of the sponge body, and are eventually extruded from
the sponge through the canals of the aquiferous system.
PMID- 29958491
TI - The rete mirabile cranica in the genus Mobula: A comparative study.
AB - Devil rays (Mobulidae) have large brains that rest in a voluminous chondrocranium
almost completely filled by a rete mirabile cranica (RMC). The RMC is a massive
arterial network grossly divisible into a "caudal RMC" supplying blood to the
brain, and an expanded, more complex "precerebral RMC" nested within the large
cranial cavity rostral to the telencephalon. Both the caudal and precerebral
retia originate from the posterior portion of the profundae cerebri arteries,
which lie ventral to the brain and form the sides of a vascular triangle, the
base of which is anterior and formed by the joining of the internal carotids; the
vertex is posterior and median, corresponding to the anterior extreme of the
spinalis impar artery. Vessels of the caudal RMC branch posteriorly from the
profundae cerebri and course over and into the brain. Vessels branching more
anteriorly course rostrally to form the precerebral RMC, which takes the shape of
the cranial cavity and completely envelops the olfactory peduncles. Large retial
arteries (1-mm diameter) branch and taper to about 50-150 MUm, forming a system
of small arteries or arterioles. Many give rise to a mesh of tertiary vessels
(precapillary arterioles or capillaries, ca. 20-50 MUm in diameter), which, along
with arterioles, are embedded in the adventitia of these arteries, with which
they communicate by numerous anastomoses. Although the function of the RMC
remains enigmatic, its complexity and fine structure are suggestive, and
hypotheses of its role are discussed.
PMID- 29958492
TI - The sphincter of the efferent filament artery in teleost gills: II. Sympathetic
innervation.
AB - In addition to the cholinergic innervation described in the sphincter of the
efferent filament arteries (Bailly and Dunel-Erb, '86), an aminergic component
has been demonstrated by specific techniques. The Falck fluorescence technique
reveals a network of nerve fibers displaying a green fluorescence characteristic
of catecholamines. At the ultrastructural level two types of fibers are present,
one with clear vesicles and another with densecored vesicles. Axo-axonal synaptic
relationships exist between the two types. Results of 5- and 6-OHDA
(hydroxydopamine) treatments confirm the presence of an aminergic component.
These observations support the notion of a dual innervation: cholinergic and
adrenergic of, respectively, parasympathetic and sympathetic origin. The presence
of presynaptic modulation is suggested. The aminergic component could inhibit or
reduce the release of acetylcholine from cholinergic nerve endings. These results
suggest that the sympathetic innervation modulates the vasoconstriction effect of
the parasympathetic component.
PMID- 29958494
TI - Quantification of Multivalency in Protein-Oligomer-Coated Nanoparticles Targeting
Dynamic Membrane Glycan Receptors.
AB - Multivalent binding of proteins to glycan receptors on the host cell
quantitatively controls the initial adhesion of most viruses. However,
quantifying such multivalency in terms of binding valency has always been a
challenge because of the hierarchy of multivalency involving multiple protein
oligomers on the virus, limiting our understanding of virus adhesion and
virulence. To address this challenge, we mimicked virus adhesion to cell surfaces
by attaching protein-oligomer-coated nanoparticles (NPs) to fluidic glycolipid
membranes with surface glycan density varying over 4 orders of magnitude. Using
total internal reflection fluorescence microscopy to track single attached NPs,
we show that the binding isotherms exhibit two regions, attributed to monovalent
and multivalent protein/glycan interactions at low and high glycan densities,
respectively. The bimodal binding curve allows the quantification of the
different valency and binding constants of monovalent and multivalent
interactions. In addition, the competitive inhibition of multivalency by the
glycopolymer presenting multiple glycan moieties is quantitatively appreciated.
This work is essential to mapping and understanding the complex binding
specificities of glycan-binding proteins and inhibitory drug designs and
applications.
PMID- 29958495
TI - Inner Surface-Functionalized Graphene Aerogel Microgranules with Static Microwave
Attenuation and Dynamic Infrared Shielding.
AB - Bulk graphene aerogels with high electrical conductivity, ultralow density, and
high specific surface area have attracted significant attention because of their
fascinating performances in energy storage, catalysis, absorption, sensor,
electromagnetic shielding, etc. However, graphene aerogel microgranules (i.e.,
reducing the size of the bulk aerogels into microscale) and their performances in
the electromagnetic field have been ignored. Herein, we report a new strategy to
make floatable graphene aerogel microgranules with high hydrophobicity (137
degrees ), low density (13.5 mg/cm3), and high specific surface area (516 m2/g).
These microgranules were synthesized initially from reduced graphene oxide (rGO)
hydrogel microparticles and then in situ-modified by silica nanoparticles.
Further investigations have demonstrated that the resulting silica-modified rGO
aerogel microgranules possess highly efficient static electromagnetic screening
(average 30.3 dB in 8-18 GHz) and dynamic infrared shielding (higher than 10 dB
during floatation in air for 15 min) properties. The work reported here should
give much inspiration to make more functional aerogel microgranules used in
various emerging fields.
PMID- 29958493
TI - Structure Dependence of Pyridine and Benzene Derivatives on Interactions with
Model Membranes.
AB - Pyridine-based small-molecule drugs, vitamins, and cofactors are vital for many
cellular processes, but little is known about their interactions with membrane
interfaces. These specific membrane interactions of these small molecules or ions
can assist in diffusion across membranes or reach a membrane-bound target. This
study explores how minor differences in small molecules (isoniazid,
benzhydrazide, isonicotinamide, nicotinamide, picolinamide, and benzamide) can
affect their interactions with model membranes. Langmuir monolayer studies of
dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylethanolamine
(DPPE), in the presence of the molecules listed, show that isoniazid and
isonicotinamide affect the DPPE monolayer at lower concentrations than the DPPC
monolayer, demonstrating a preference for one phospholipid over the other. The
Langmuir monolayer studies also suggest that nitrogen content and stereochemistry
of the small molecule can affect the phospholipid monolayers differently. To
determine the molecular interactions of the simple N-containing aromatic
pyridines with a membrane-like interface, 1H one-dimensional NMR and 1H-1H two
dimensional NMR techniques were utilized to obtain information about the position
and orientation of the molecules of interest within aerosol-OT (AOT) reverse
micelles. These studies show that all six of the molecules reside near the AOT
sulfonate headgroups and ester linkages in similar positions, but nicotinamide
and picolinamide tilt at the water-AOT interface to varying degrees. Combined,
these studies demonstrate that small structural changes of small N-containing
molecules can affect their specific interactions with membrane-like interfaces
and specificity toward different membrane components.
PMID- 29958496
TI - Acetylated Polyethylenimine-Entrapped Gold Nanoparticles Enable Negative Computed
Tomography Imaging of Orthotopic Hepatic Carcinoma.
AB - Developing an effective computed tomography (CT) contrast agent is still a
challenging task for precise diagnosis of hepatic carcinoma (HCC). Here, we
present the use of acetylated polyethylenimine (PEI)-entrapped gold nanoparticles
(Ac-PE-AuNPs) without antifouling modification for negative CT imaging of HCC.
PEI was first linked to fluorescein isothiocyanate (FI) and then utilized as a
vehicle for the entrapment of AuNPs. The particles were then acetylated to reduce
its positive surface potential. The designed Ac-PE-AuNPs were characterized by
various techniques. We find that the Ac-PE-AuNPs with a uniform size distribution
(mean diameter = 2.3 nm) are colloidally stable and possess low toxicity in the
studied range of concentration. Owing to the fact that the particles without
additional antifouling modification were mainly gathered in liver, the Ac-PE
AuNPs could greatly improve the CT contrast enhancement of normal liver, whereas
poor CT contrast enhancement appeared in liver necrosis region caused by HCC. As
a result, HCC could be easily and precisely diagnosed. The designed Ac-PE-AuNPs
were demonstrated to have biocompatibility through in vivo biodistribution and
histological studies, hence holding an enormous potential to be adopted as an
effective negative CT contrast agent for diagnosis of hepatoma carcinoma.
PMID- 29958497
TI - Thermoreversible Surface Polymer Patches: A Cryogenic Transmission Electron
Microscopy Investigation.
AB - Hybrid core-shell type nanoparticles from gold nanoparticle cores and poly( N
isopropylacrylamide) shells were investigated with regard to their structural
plasticity. Reversible addition-fragmentation chain transfer polymerization was
used to synthesize well-defined polymers that can be readily anchored onto the
gold nanoparticle surface. The polymer shell morphologies were directly
visualized in their native solution state at high resolution by cryogenic
transmission electron microscopy, and the microscopic results were further
corroborated by dynamic light scattering. Different environmental conditions and
brush architectures are covered by our experiments, which leads to distinct
thermally induced responses. These responses include constrained dewetting of the
nanoparticle surface at temperatures above the lower critical solution
temperature of poly( N-isopropylacrylamide), leading to surface polymer patches.
This effect provides a novel approach toward breaking the symmetry of
nanoparticle interactions, and we show first evidence for its impact on the
formation of colloidal superstructures.
PMID- 29958498
TI - Stabilization of dry protein coatings with compatible solutes.
AB - Exposure of protein modified surfaces to air may be necessary in several
applications. For example, air contact may be inevitable during the implantation
of biomedical devices, for analysis of protein modified surfaces, or for sensor
applications. Protein coatings are very sensitive to dehydration and can undergo
significant and irreversible alterations of their conformations upon exposure to
air. With the use of two compatible solutes from extremophilic bacteria, ectoine
and hydroxyectoine, the authors were able to preserve the activity of dried
protein monolayers for up to >24 h. The protective effect can be explained by the
preferred exclusion model; i.e., the solutes trap a thin water layer around the
protein, retaining an aqueous environment and preventing unfolding of the
protein. Horseradish peroxidase (HRP) immobilized on compact TiO2 was used as a
model system. Structural differences between the compatible solute stabilized and
unstabilized protein films, and between different solutes, were analyzed by
static time-of-flight secondary ion mass spectrometry (ToF-SIMS). The biological
activity difference observed in a colorimetric activity assay was correlated to
changes in protein conformation by application of principal component analysis to
the static ToF-SIMS data. Additionally, rehydration of the denatured HRP was
observed in ToF-SIMS with an exposure of denatured protein coatings to ectoine
and hydroxyectoine solutions.
PMID- 29958499
TI - Service provision in Scotland for people with an intellectual disability who
have, or are at risk of developing, dementia.
AB - This research aimed to identify current national provision by health services in
Scotland in relation to proactive screening and reactive assessment for people
with an intellectual disability in Scotland who have, or are at risk of
developing, dementia. Staff from 12 intellectual disability services,
representing the 11 health board areas in Scotland, completed an online
questionnaire which asked about proactive screening and reactive assessment for
people with intellectual disability who had, or were at risk of developing,
dementia as well as suggested areas for improvement. All of the areas provided
services for people with intellectual disability who have, or are at risk of
developing, dementia, but differed as to whether this was reactive, proactive or
both. Nine services offered intervention following diagnosis. The most common
elements used across both proactive screening and reactive assessment were
conducting a health check, using a general dementia questionnaire designed for
people with an intellectual disability and direct assessment with the person.
Clinical psychology and community learning disability nurses were the professions
most likely to be involved routinely in both proactive screening and reactive
assessments. The psychometric properties of the most commonly used assessments of
cognitive and behavioural functioning were mixed. The areas of improvement
suggested by practitioners mainly related to ways of improving existing pathways.
This research represents the first step in providing an overview of service
provision in Scotland. There was some inconsistency in relation to the general
and specific components which were involved in proactive screening and reactive
assessment. Implications for service provision are discussed.
PMID- 29958500
TI - Thrombopoietin mimetics for systemic lupus erythematosus with antiphospholipid
antibodies should be discussed separately.
PMID- 29958501
TI - Combination of rituximab and abatacept as an exit strategy for repetitive B-cell
depletion in children with severe autoimmune diseases: a report of three cases.
PMID- 29958502
TI - Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis,
predicts the development of proteinuric flare.
AB - Lupus nephritis (LN) is a major complication of systemic lupus erythematosus
(SLE). Conventional biomarkers for assessing renal disease activity are imperfect
in predicting clinical outcomes associated with LN. The aim of this study is to
identify urinary protein biomarkers that reliably reflect the disease activity or
predict clinical outcomes. A quantitative proteomic analysis was performed to
identify protein biomarker candidates that can differentiate between SLE patients
with and without LN. Selected biomarker candidates were further verified by
enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE
patients ( n = 121) to investigate their predictive values for LN activity
measure. Furthermore, the association between urinary levels of a selected panel
of potential biomarkers and prognosis of LN was assessed with a four-year follow
up study of renal outcomes. Urinary vitamin D-binding protein (VDBP),
transthyretin (TTR), retinol binding protein 4 (RBP4), and prostaglandin D
synthase (PTGDS) were significantly elevated in SLE patients with LN, especially
in patients with active LN ( n = 21). Among them, VDBP well correlated with
severity of proteinuria (rho = 0.661, p < 0.001) and renal SLE Disease Activity
Index (renal SLEDAI) (rho = 0.520, p < 0.001). In the four-year follow-up, VDBP
was a significant risk factor (hazard ratio 9.627, 95% confidence interval 1.698
to 54.571, p = 0.011) for the development of proteinuric flare in SLE patients
without proteinuria ( n = 100) after adjustments for multiple confounders.
Urinary VDBP correlated with proteinuria and renal SLEDAI, and predicted the
development of proteinuria.
PMID- 29958503
TI - Paper shredder machines: a danger to little fingers. A case of triple finger
amputation in a 2-year-old boy.
PMID- 29958504
TI - Aging and chromatoid body assembly: Are these two physiological events linked?
AB - The chromatoid body is a cytoplasmic male germ cell structure that plays a role
in the regulation of mRNA transcription during spermatogenesis. A proteomic
analysis of this structure has identified the presence of its classic molecular
markers (MVH and MIWI), as well as a significant number of transient proteins.
Circadian locomotor output cycles protein kaput (CLOCK) and brain and muscle ARNT
like 1 (BMAL1), which are molecular components of the circadian clock, are likely
located in the chromatoid body in a transient fashion. This study sought to
determine whether aging produces morphological changes in the chromatoid bodies
of round spermatids similar to those previously observed in BMAL1 knockout mice.
A sample of 30 male mice was divided into three groups: juvenile mice (45 days
old), adult mice (120 days old), and old mice (+180 days old). Aging was
confirmed by viability and sperm count analyses and testosterone dosage. Squash
slides prepared with fragments of seminiferous tubules were immunostained for
MVH, MIWI, BMAL1, and CLOCK detection. In juvenile and adult specimens, single
round chromatoid bodies were observed using MVH/BMAL1 and MIWI/CLOCK
immunostaining. In old specimens, many chromatoid bodies displayed changes in
number and morphology, as well as an increase in the interactions between MVH and
BMAL1; MIWI and CLOCK. Changes in chromatoid body morphology increased
interactions between the proteins analyzed herein, and decreased amounts of these
proteins in seminiferous tubules of older mice may indicate that aging influences
the assembly and physiology of chromatoid bodies, which may, in turn, affect
fertility. Impact statement The results discussed in this paper indicate that
aging compromises the structure and physiology of chromatoid bodies (CBs) in post
meiotic male cells. Since CB is a fundamental structure for the differentiation
of the mature male germ cell it is possible that this imbalance in CB physiology
may play a role in the reduction of fertility in older men. It is important to
note that not only the classic CB markers (such as the MIWI and MVH proteins)
were used to showcase the structural changes in the CBs but also the main
components of circadian cycle control (the CLOCK and BMAL1 proteins), indicating
that the reduction of circadian control in aged males may contribute to these
changes in CBs as well. Therefore, it is intriguing to evaluate the hypothesis
that controlling these physiological/structural changes in CBs may be a way of
delaying the effects of aging in males.
PMID- 29958505
TI - A questionnaire-based analysis of parental perspectives on pediatric cochlear
implant (CI) re/habilitation services: a pilot study from a developing CI service
in India.
AB - OBJECTIVE: To study parental perspectives on re/habilitation services offered for
pediatric cochlear implant (CI) users at a non-profit organization in India.
METHODOLOGY: A non-standardized questionnaire comprising 46 items was created to
understand perspectives of parents of pediatric CI users. Questions were designed
to examine re/habilitation services from the angles of service delivery, parental
stress levels, reasons for delay in obtaining services, sources of emotional
support, concerns, and fears during each stage starting from diagnosis of hearing
loss to CI surgery, re/habilitation services and parents' views of their children
post-CI. The questionnaire was posed to 30 parents and responses were recorded
and coded. RESULTS AND DISCUSSION: Qualitative and quantitative analyses based on
parents' responses identified several factors that significantly influenced
parental perspectives during each stage. The major factors delaying the decision
to go for CI included a fear of surgery, lack of funds for CI and the subsequent
re/habilitation process, and limited knowledge. Key concerns were the child's
academic performance and social acceptance. Familial support played an important
role during each stage. A significant reduction in the parental stress levels was
observed following CI surgery. Parents indicated that local support for therapy,
financial assistance and better guidance at each stage would substantially help
in lowering stress levels. CONCLUSIONS: The parental perspectives analyzed in
this study can be utilized towards improving the quality of service delivery in
terms of parental satisfaction and outcomes post-CI. Efforts should be taken to
improve parental awareness, funding options, and access to re/habilitation
services and social networks connecting similar parents.
PMID- 29958506
TI - Comparison of closed system transfer devices for turnaround time and ease of use.
AB - Objective/purpose The primary purpose of this study was to compare three closed
system transfer devices with differing mechanical interfaces for their
suitability for adoption into our daily practice. The secondary purpose was to
use the results of this study to support the selection of one of the closed
system transfer devices, which would suit both the pharmacy and nursing staff at
our institution, furthermore promoting the enculturation of international
recommendations into our clinical practice. Study design/methods The hazardous
drug preparation process was observed and timed continuously from the moment the
technician started compounding until the finished product was handed to the
designated checker by raising hands. A self-administered, structured
questionnaire was used for data collection looking at ease of use of each of the
devices from the perspective of pharmacy technicians and nurses. The
questionnaire contained an open-ended 10-point Likert-type scale of eight
domains. Results/key findings An improvement in the compounding efficiency of
hazardous drugs using PhaSealTM ( n = 46), ChemoLockTM ( n = 45), and
EquaShield(r) II ( n = 45), when compared respectively against the historical
control ( n = 86), was statistically significant ( p < 0.001). However, no
statistically significant difference among the different closed-system transfer
devices for preparation of hazardous drugs was observed in our study ( p = 0.1).
In terms of ease of use, there was no difference in preference for ChemoLockTM
and Equashield(r)II among the pharmacy technicians with both scoring a mean score
of 10 with regard to implementation. While PhaSealTM scored a mean score of 7.2.
Among the nursing staff there was a slight preference for ChemoLockTM over
Equashield(r)II with a mean score of 9.2 and 9, respectively with regard to the
recommended product, while PhaSealTM scored a mean score of 7.4. Both nursing
staff and pharmacy technicians had a preference ChemoLockTM, with a mean score of
10 and 9.6, respectively in terms of on how easy was each device/system to use
and overall impression for pharmacy technicians. This was followed by
Equashield(r)II with a mean score of 9.8 and 8.6, respectively and then PhaSealTM
with a mean score of 7.2 and 6.6, respectively. Pharmacy technicians felt there
were more steps, packaging and clutter when using PhaSeal(r) in comparison to the
other devices. With Equashield(r) II, the estimation of clutter was higher than
that of ChemoLockTM despite the number of packages being within a similar range.
Conclusion/recommendations Our study found that with experienced staff,
compounding of hazardous drugs with closed-system transfer devices can be as
efficient as or even more so than with the traditional needle and syringe method.
With the lack of statistically significant difference among the different closed
system transfer devices studied, in addition to the cost, ease of use was one of
the factors that decided the products applicability in our institution.
PMID- 29958507
TI - A 20-year (1996-2015) trend in deaths as a result of burns in the Transkei
subregion of South Africa.
AB - Background Deaths as a result of burns are unrecognised, under-reported and
therefore under-estimated, especially in rural areas such as the Transkei
subregion of South Africa. Burning to death is painful and preventable. Objective
The aim of this study was to investigate a 20-year trend in deaths as a result of
burns in the Transkei subregion of South Africa. Method A record review
descriptive study was undertaken of all medico-legal autopsies performed from
1996 to 2015 at Mthatha Forensic Pathology Laboratory. Results In total 22,952
medico-legal autopsies were conducted at Mthatha Forensic Pathology Laboratory
from 1996 to 2015. Of these, 689 (3%) were burn related. This gives an average of
eight deaths resulting from burns per 100,000 of the population annually in this
region. The highest rate (11.6/100,000) was recorded in 2007, and the lowest
(3.3/100,000) in 2004. Males outnumbered females at a ratio of 1.6:1. Young
children of aged 10 years old or younger accounted for 130 of the victims,
amounting to a death rate of 1.51/100,000. Conclusion The number of deaths as a
result of burning has more than doubled in the last 20 years (1996-2015) in the
Transkei subregion of South Africa. Action to prevent these deaths is urgently
required.
PMID- 29958508
TI - Smoking reduces the efficacy of belimumab in mucocutaneous lupus.
AB - OBJECTIVES: Recently, we demonstrated a negative impact of smoking on belimumab
efficacy in patients with systemic lupus erythematosus (SLE). Here, we
particularly investigated clinical effects of belimumab and a potential impact of
smoking in mucocutaneous and articular SLE. METHODS: We surveyed 62 SLE patients
treated between 2011 and 2017. Evaluation included the mucocutaneous descriptors
of SLEDAI-2K (rash, alopecia, mucosal ulcers; mcSLEDAI-2K), CLASI, the arthritis
SLEDAI-2K descriptor (arSLEDAI-2K) and the 28-joint count. RESULTS: mcSLEDAI-2K
and CLASI activity decreased from baseline to month 6 and 12 (P < 0.001 for all).
No worsening in CLASI damage was observed. Current or previous smokers displayed
a higher probability of unchanged/worsened mcSLEDAI-2K compared to never smokers
(OR: 6.4; 95% CI: 1.5-27.4; P = 0.012), also after adjustment for antimalarial
agents. arSLEDAI-2K scores had decreased at month 6 (P < 0.001) and 12 (P <
0.001). Likewise, tender and swollen 28-joint counts had improved at month 6 (P =
0.010 and P < 0.001, respectively) and 12 (P = 0.001 for both). We observed no
impact of smoking on belimumab efficacy in articular SLE. CONCLUSION: We observed
a negative impact of smoking on the efficacy of belimumab in mucocutaneous SLE.
In contrast, no impact of smoking on belimumab efficacy was seen in patients with
articular manifestations.
PMID- 29958509
TI - Psychotherapy for eating disorders: A meta-analysis of direct comparisons.
AB - OBJECTIVE: We conducted a meta-analysis of randomized controlled trials (RCTs) of
bona fide psychotherapy for adults with eating disorders (EDs). METHOD: Thirty
five RCTs with 54 direct comparisons were included. The majority of RCTs included
participants with bulimia nervosa and/or binge-ED, while only two RCTs included
participants with anorexia nervosa, and three RCTs included participants with an
ED not otherwise specified. RESULTS: There was a clear advantage of bona fide
psychotherapy over wait-list controls. Bona fide psychotherapy was superior to
non-bona fide treatment; however, the majority of results were not stable. There
were no significant differences between bona fide cognitive-behavioral therapy
(CBT) and bona fide non-CBT, with the exception of bona fide CBT resulting in
greater reductions in ED psychopathology assessed by the ED Examination, which
primarily assesses maintenance factors according to the CBT model. CONCLUSIONS:
Generally, the results indicate that any bona fide psychotherapy will be equally
effective. While the number of trials remains modest, we hope that as more
research becomes available, treatment guidelines can be updated, and more
evidence-based treatment options will be available for treating EDs.
PMID- 29958510
TI - Application of MRS- and ASL-guided navigation for biopsy of intracranial tumors.
AB - Background The diagnosis of a tumor depends on accurate identification of the
target area for biopsy. However, tumor heterogeneity and the inability of
conventional structural data for identifying the most malignant areas can reduce
this accuracy. Purpose To evaluate the feasibility and practicality of magnetic
resonance spectroscopy (MRS)- and arterial spin labeling (ASL)-guided MRI
navigation for needle biopsy of intracranial tumors. Material and Methods Thirty
patients with intracranial tumors who underwent intraoperative stereotactic
biopsy were retrospectively analyzed. Contrast-enhanced 3D-BRAVO or 3D-T2FLAIR
structural data, combined with MRS and ASL data, were used to identify the target
area for biopsy. High-choline or high-perfusion sites were chosen preferentially,
and then the puncture trajectory was optimized to obtain specimens for
histopathologic examination. Results Twenty-two specimens were collected from 20
glioma patients (two specimens each were collected from two patients) and ten
specimens were collected from ten lymphoma patients. The diagnosis rate after the
biopsy was 93.3% (28/30). Two gliomas were initially diagnosed as gliosis and
subsequently diagnosed correctly after the collection of a second biopsy
specimen. Combined MRS and ASL helped target selection in 23 cases (76.7%),
including three cases each of low-enhancing and non-enhancing gliomas. In two
cases, the target selection decision was changed because the areas initially
chosen on the basis of positron emission tomography data did not match the high
perfusion areas identified with ASL. Conclusion Compared with conventional MRI,
combined MRS and ASL improved the accuracy of target selection for the
stereotactic biopsy of intracranial tumors.
PMID- 29958511
TI - Myocardial Infarct After Marijuana Inhalation in a 16-year-old Adolescent Boy.
AB - Many reports of marijuana-associated myocardial infarct (MI) are limited by
incomplete evaluation of the toxicologic exposure, a lack of definitive anatomic
findings, and the potential for comorbid coronary atherosclerosis inherent in an
adult population. We report a 16-year-old adolescent boy who presented with chest
pain after smoking marijuana and was found to have acute MI. Electrocardiogram
showed diffuse ST-segment elevations. Exhaustive toxicologic testing confirmed
the presence of Delta-9-tetrahydrocannabinol metabolite and ruled out other drugs
of abuse. Echocardiography demonstrated moderate global left ventricular systolic
dysfunction. Coronary angiography demonstrated no focal coronary lesions or
obstruction. Right ventricular septal endomyocardial samples biopsied 36 hours
after the onset of pain showed a subendocardial acute MI with a sparse
neutrophilic infiltrate. One month after the event, magnetic resonance imaging
showed a severely dilated left ventricle and moderately to severely depressed
global systolic function. Late gadolinium enhancement consistent with myocardial
fibrosis was seen in nearly all myocardial segments. Our unusually well
documented findings strengthen the potential association between marijuana and
MI. Furthermore, we demonstrate a disease distribution supporting a process that
affects the coronary circulation globally, likely at the distal, small-vessel
level.
PMID- 29958512
TI - Attachment as a Core Feature of Resilience: A Systematic Review and Meta
Analysis.
AB - Background Research has pointed to secure attachment as a possible key factor of
resilience in adulthood. Objective We aimed to investigate the role of secure
attachment as a potential core feature in the properties of resilience. Methods
We conducted a systematic review in accordance with PRISMA guidelines followed by
a meta-analysis. Results Thirty-three studies were included in the review, and 10
of these, including 2305 subjects, were used for meta-analysis. The raw
correlation coefficients ranged from .20 to .57, which indicated weak to moderate
correlations between resilience and attachment. The synthesized correlation
coefficients indicated that the correlations were significant and highly unlikely
to be due to random variation. All studies are also reported on qualitatively.
Conclusions In both of our meta-analyses and in the narratively reported studies,
we found that secure attachment is associated with the presence of resilience.
PMID- 29958513
TI - Emotional Response Categorization in Adolescents and Young Adults.
AB - Categorization is based on cognitive mechanisms allowing the development of
internal representations of the environment that guide behavior. This study tests
the influence of emotions on categorization in adolescents and young adults.
After a mood induction (negative, positive, or neutral), we compared how 68
adolescents aged 13 to 15 and 57 young adults aged 21 to 29 categorized emotional
concepts using a lexical emotional categorization task. Participants had to
choose which of three associates, of different emotional valence (positive,
negative or neutral), was more similar to a target concept. The aim of this study
was to determine if adolescents rely on the emotional dimension in categorization
more than adults. The results show that the emotional state can influence the
cognitive process of categorization in adolescence, particularly in the negative
mood.
PMID- 29958514
TI - Gritty Leaders: The Impact of Grit on Positive Leadership Capacity.
AB - The concepts of grit and positive leadership are central to extraordinary
performance. However, to date there has been little empirical analysis of the
relationship between a leader's level of grit and their capacity to implement
positive leadership strategies and practices. This correlational study explores
these linkages, taking grit subfactors into consideration as well as three
dimensions of positive leadership. Convenience sampling was used to survey 100
leaders across a range of industries. Respondents completed the Grit Scale and 18
questions from the Positive Leadership Practices Self-Assessment. Results
indicated that grit positively correlated with positive leadership, and
perseverance exhibited a stronger relationship than passion. Further, grit
accounted for variance in positive leadership. These findings provide a solid
evidence base for giving leaders access to development opportunities that can
accelerate the growth of grit and positive leadership.
PMID- 29958515
TI - Relationships Amongst Aggression, Self-Theory, Loneliness, and Depression in
Emerging Adults.
AB - The purpose of this study was to examine the relationships amongst aggression,
self-theory, loneliness, and depression. The study group consisted of 904 student
volunteers from various undergraduate programs of a university in Central
Anatolia. Simple and hierarchical multiple linear regression analyses, as well as
t-tests, were used to analyze the data. In the preliminary analysis performed,
females' depression levels and males' aggression levels are higher. The study
findings revealed that self-theory negatively and significantly predicted
aggression, whereas loneliness and depression positively and significantly
predicted aggression in emerging adulthood. Another important finding showed that
both direct and indirect relationships exist between self-theory and aggression.
According to these findings, loneliness and depression play partially mediating
roles individually, and fully mediating roles together, with regard to the
relationship between self-theory and aggression.
PMID- 29958516
TI - Routine Psychological Testing of the Individual Is Not Valid.
AB - In this article, we present and argue our assertion that current routine
psychological testing of individuals is not valid. To support our assertion, we
review the concept of ergodicity, Birkhoff's theorem, and Molenaar's manifesto,
which together support our contention that the direct transposition of population
estimations for producing inferences about the individual is not valid. We argue
that this practice of direct transposition is the root cause of why routine
psychological testing of individual is not valid. We then provide an example of a
common application of psychological testing of an individual, explaining why this
practice is not valid. Finally, we discuss how the intraindividual (or within
person) approach provides some prospect for valid individual testing and also
introduces new challenges. We hope that our questioning of current psychological
testing practices motivates researchers to propose and study novel methodological
propositions to address the issues raised by our assertion.
PMID- 29958517
TI - Effect of single-nucleotide polymorphisms on the breeding value of fertility and
breeding value of beef in Hungarian Simmental cattle.
AB - The objective of this study was to estimate the effect of single-nucleotide
polymorphisms (SNPs) on the breeding value of fertility (BVF) and the breeding
value of beef (BVB) in Hungarian Simmental cattle. Genotypes were determined on a
high-density Illumina Bovine DNA Chip. Data screening and data identification
were performed by multi-locus mixed-model. Statistical analyses were carried out
to find associations between individual genotypes and the investigated quality
values. Three loci showed considerable association with BVF (-log10 P = 9.5, 9.9
and 14.5, respectively) on chromosomes 9, 28 and 29, respectively. The
frequencies of their minor alleles (MAF) were 0.375, 0.355 and 0.354,
respectively. Two loci showed association with BVB (-log10 P = 25.3 and 22.7) on
chromosomes 2 and 11, respectively (their MAF were 0.438 and 0.229). The
abovementioned loci provide a straightforward possibility to assist selection by
molecular tools.
PMID- 29958518
TI - Analysis of the immune response of calves to various saponin-based adjuvants for
an experimental Mycoplasma bovis vaccine.
AB - Mycoplasma bovis is a primary infectious agent of many disorders in cattle
including bovine respiratory disease. No commercial vaccines against M. bovis are
available in Europe. The immune response of calves to three saponin-based
adjuvants combined with a field Polish M. bovis strain was evaluated. Four groups
of six calves each were injected subcutaneously with the M. bovis strain combined
with either saponin, saponin + Emulsigen(r), saponin + Emulsigen(r) +
alphatocopherol acetate, or with phosphate-buffered saline as control group.
Blood and nasal swab samples were collected up to day 84 post injection. All
formulations effectively stimulated the humoral and the cellular immune response
of the calves, but the course of the response depended on the adjuvant
formulation. These immunological data provide additional information supporting
the findings of previous M. bovis saponin and Emulsigen(r) vaccine challenge
studies to facilitate the development of successful M. bovis vaccines.
PMID- 29958519
TI - Variations in the detection of anti-PEDV antibodies in serum samples using three
diagnostic tests - short communication.
AB - Over the last few years several porcine epidemic diarrhoea (PED) outbreaks have
been discovered in Europe including the first PED case in Slovenia in January
2015. The aim of this study was to determine when PED virus (PEDV) infection
started in Slovenia. Serum samples collected between 2012 and 2016 were tested.
Three hundred and seventy-five serum samples were collected from 132 Slovenian
small, one-site pig farms. Samples were tested for PEDV antibodies utilising
three different serological methods: commercially-available indirect ELISA, in
house blocking ELISA test and Immunoperoxidase Monolayer Assay (IPMA) test. One
hundred and seventy (45.33%) tested samples were found positive by the
commercially-available ELISA test kit, and 10 (5.68%) of these 170 samples found
positive were positive by the in-house blocking ELISA. Only these 10 samples were
collected from a farm where clinical signs of PED infection had been observed and
PEDV was confirmed by RT-PCR methodology; the other 160 samples were collected
randomly. Thirty-two samples with the highest S/P value obtained with the
commercial ELISA were all negative with IPMA. Reasons for the high variance in
the results obtained remain unclear; more research is required to ensure higher
sensitivity and specificity in terms of PEDV antibody tests and other PED
diagnostic methods.
PMID- 29958520
TI - Myxidium shedkoae Sokolov, 2013 (Myxozoa: Myxidiidae), a parasite of the
gallbladder of Perccottus glenii Dybowski, 1877 (Actinoptrygii: Odontobutidae):
Supplementary data on morphology and phylogenetic position based on 18s rDNA
sequence analysis.
AB - This paper is the first report on the molecular characterisation of myxozoan
parasites from the odontobutid fish Chinese (Amur) sleeper (Perccottus glenii
Dybowski, 1877). The authors determined the partial 18S rDNA sequence of Myxidium
shedkoae Sokolov, 2013 from the gallbladder of the fish. Phylogenies
reconstructed using maximum likelihood and Bayesian inference analysis revealed
that M. shedkoae belongs to the hepatic biliary group of myxozoans (after
Kristmundsson and Freeman, 2013) as a member of the clade consisting of
Zschokkella sp. KLT-2014, Myxidium truttae and Zschokkella nova. Some new
morphological features of the parasite are also presented.
PMID- 29958521
TI - Hippocampal necrosis and sclerosis in cats: A retrospective study of 35 cases.
AB - Hippocampal necrosis and hippocampal sclerosis in cats is a neuropathological
entity which is a major concern in feline epilepsy. The aim of our study was to
identify associated pathologic brain lesions possibly serving as aetiological
triggers in this condition. Therefore, the formalin-fixed and paraffin
waxembedded brain tissue of 35 cats diagnosed with hippocampal necrosis or
sclerosis was examined retrospectively. In 26 cats inflammatory infiltrates could
be found in the hippocampus or adjacent brain regions. Fifteen out of these
animals demonstrated mild to moderate infiltrations by lymphocytes and complement
deposition in the hippocampus similar to human limbic encephalitis, seven showed
unspecific, predominantly non-suppurative inflammation, and two demonstrated
suppurative inflammation of the hippocampus or adjacent brain regions.
Additionally, one cat was diagnosed with central nervous manifestation of feline
infectious peritonitis virus and another one with cerebral Toxoplasma gondii
infection. Intracranial neoplasia was present in five cases altogether. Three of
them comprised meningioma which was present additionally to lesions resembling
limbic encephalitis in two cases, and a dentate gyrus alteration in one case. The
other two tumour-associated cases comprised oligodendroglioma. Structural
alterations of the dentate gyrus together with hippocampal sclerosis were
encountered in three cases in total. Besides the case associated with a
meningioma, one case demonstrated lesions resembling limbic encephalitis. A
vascular infarct in the temporal lobe was encountered in one cat. In four cases
no lesions other than hippocampal necrosis or sclerosis were found. The
involvement of feline immunodeficiency virus infections, which may be able to
produce hippocampal lesions, was not encountered in the cats examined.
PMID- 29958522
TI - Cross section of gill filaments in histological preparations helps better
identification of the location of myxosporean plasmodia in gill tissues.
AB - Location and tissue preference of filamental-type myxosporean plasmodia in
histological slides of the gills can be properly identified only in cross
sections of the gill filaments. The authors selected three myxosporeans
(Myxobolus rutili, M. dispar and Henneguya psorospermica, parasites of the roach,
the common carp and the pike, respectively) for studying the problem. The
plasmodia of these species studied in longitudinal sections were earlier regarded
as developing inside the filamental arteries. Cross sections of the filaments
showed that all the three species developed plasmodia in the dense connective
tissue constituting the adventitia of gill arteries and covering the
cartilaginous gill rays. Myxobolus rutili started its development close to the
afferent branchial artery but attached to the cartilaginous gill ray. More
developed plasmodia of this species surrounded the rays. Plasmodia of M. dispar
were formed on the inner side of the afferent branchial artery, while those of H.
psorospermica were located at the external side of the efferent branchial artery.
PMID- 29958523
TI - Myxobolus infection in the cornea of the roach (Rutilus rutilus) in Lake Balaton.
AB - Infection of the cornea in fishes by Myxobolus plasmodia is a common but still
little known site preference of myxosporeans. A sporadic but striking infection
in the cornea of the roach (Rutilus rutilus) was observed in Lake Balaton,
Hungary. Relatively small, round plasmodia 250 to 500 MUm in diameter developed
in the dense connective tissue of the cornea. Morphological and molecular
biological examination of spores collected from cysts in the cornea demonstrated
that this infection is caused by Myxobolus fundamentalis, a species hitherto
reported only from the cartilaginous gill arch of the roach. The 18S rDNA
sequences of spores from the cornea showed 99.9% identity to the sequences of
spores from the gill arch, and they also shared 99.9% identity with the sequences
of triactinomyxon actinospores obtained from the oligochaete Isochaetides
michaelseni.
PMID- 29958524
TI - Evaluation of Pgp (MDR1) immunohistochemistry in canine lymphoma - prognostic and
clinical aspects.
AB - Permeability glycoprotein (P-glycoprotein, Pgp) immunohistochemistry (IHC) was
evaluated in dogs with multicentric lymphoma treated with cyclophosphamide-
doxorubicin-vincristine-prednisolone with or without L-Asparaginase. Lymph nodes
of 33 untreated dogs were immunophenotyped: Ki67% and Pgp analyses (with anti
Pgp, monoclonal mouse C494 clone) were performed. Pgp positivity rate and
intensity were determined microscopically (by manual counting done by two blinded
authors in two parallel specimens). The median overall survival time (OST) was
333 days and the relapse-free period (RFP) 134 days. Pgp expressions were
positive in 18 out of 33 (54.5%) of tumour cells. T-cell types stained more
intensively. Lower OST and RFP were found with Pgp positivity >= 35% (OST: 240
days, RFP: 95 days) compared to Pgp positivity < 35% (OST: 428 days, RFP: 232
days). Intensive staining was associated with a lower OST and RFP (240 and 103
days, respectively) than weak staining (428 and 221 days, respectively). Death
due to adverse drug reactions was best predicted at Pgp positivity <= 6.5%
(sensitivity/specificity: 0.55/0.81) and <= 123 days (sensitivity/ specificity:
0.55/0.86). Pgp evaluation by IHC can have prognostic value with a properly
established Pgp% positivity cut-off value in dogs treated with Pgp substrate
drugs.
PMID- 29958525
TI - Molecular epidemiology of Brucella melitensis strains causing outbreaks in
Croatia and Bosnia and Herzegovina.
AB - The most recent data on the incidence of brucellosis in Southeast Europe prove
the persistence of this zoonosis in the area, regardless of constant efforts at
controlling it as one of the most dangerous zoonoses. Forty-three Brucella
melitensis strains were collected from cattle, sheep, goats and humans from
Croatia as well as Bosnia and Herzegovina between 2009 and 2015. The strains were
identified and genotyped in order to determine their epidemiological background.
Standard biotyping methods and Bruce-ladder were used to identify the strains.
Genotyping was done using multilocus variable number tandem repeats analysis
(MLVA) on 16 and multilocus sequence typing analysis (MLST) on nine loci. Results
were compared to each other and to internationally available data. Twenty- five
novel genotypes and two sequence types were identified. All tested strains, apart
from vaccine and reference strains, showed very close phylogenetic and geographic
relationships. The genotyping results indicate the endemicity of brucellosis in
this region. MLST showed no variation, confirming the stability of housekeeping
genes. The results confirm already established routes of disease spread in this
area, showing that a more detailed and vigorous control of this zoonosis is
necessary.
PMID- 29958526
TI - Detection of pregnancy in sheep using an ELISA for pregnancy-specific protein B.
AB - The early detection of pregnancy and the determination of fetal numbers have
economic benefits in sheep production because of the seasonal breeding patterns
where missing a breeding opportunity means the loss of one productive year. The
purpose of this study was to evaluate the efficacy of the B6-HRP ELISA for ovine
pregnancy-specific protein B (oPSPB) measurement in the detection of pregnancy
and estimation of fetal numbers in different sheep breeds. BioPRYN(r) ELISA assay
kit was used for the detection of pregnancy in the experimental animals. Ninety
three ewes of three breeds (British Milksheep - BM, Lacaune - L and Transylvanian
Racka - TR), each from three farms in Hungary, were included in the study. BM and
L ewes were artificially inseminated (AI). Thirty-five days after AI, all ewes
were examined by transabdominal ultrasound. The TR flock was mated naturally over
a six-week period. At the end of the mating period, the ewes were similarly
examined by ultrasound. Blood samples were taken from all pregnant ewes twice (35
and 65 days after AI), and serum samples were assayed by the BioPRYN test. It can
be concluded that the detection of serum PSPB by ELISA is a much easier, safer,
less expensive and highly accurate method for the detection of ovine pregnancy.
Although some breed-related differences were detectable at 35 and 65 days post
breeding, no differences in oPSPB levels were found in pregnant ewes carrying
different numbers of fetuses.
PMID- 29958527
TI - Assessment of corneal and conjunctival metaplasia by impression cytology during
the treatment of canine keratoconjunctivitis sicca.
AB - The purpose of this study was to assess the condition of cells in the conjunctiva
and corneal epithelium prior to and during cyclosporine- or tacrolimusbased
treatment of keratoconjunctivitis sicca (KCS). The study was performed on 40 dogs
with KCS. The dogs were divided into two groups of 20 animals each. In Group I,
0.75% cyclosporine eye drops were administered three times a day, while in Group
II 0.02% tacrolimus eye drops were administered twice daily. Additionally, each
group was subdivided into three subgroups based on the results of the Schirmer I
tear test (STT I). Evaluation of cellular metaplasia in the cornea and the
palpebral and bulbar conjunctiva based on the Nelson-Adams scale was performed by
impression cytology using Millipore round filters (Millipore VSWP 01300 DA) of 25
MUm pore diameter applied to the studied area. Ophthalmological and cytological
examinations were performed prior to the treatment as well as after one and two
months of therapy. In both groups, a decrease in Nelson-Adams values was
observed, corresponding to the increasing STT values [Rxy Spearman statistically
significant correlation coefficient values between -0.75 (P < 0.001) and -0.45 (P
< 0.01)]. The absence of goblet cells was observed in all dogs, regardless of the
KCS stage. Goblet cells reappeared following both tacrolimus- and cyclosporine
based treatment in impression cytology specimens classified as 0 in the Nelson
Adams scale. The extent of corneal and conjunctival metaplasia in the course of
tacrolimus- and cyclosporine-based treatment of KCS decreases with increasing STT
values.
PMID- 29958529
TI - Tyrosine kinase expression analyses in canine mammary gland tumours - A pilot
study.
AB - Messenger RNA levels of oncogenic tyrosine kinases were determined in canine
mammary tumours using real-time RT-PCR. The following tyrosine kinases and
vascular endothelial growth factors (VEGF) were examined in malignant and healthy
mammary tissues of 13 dogs: VEGFR1, VEGFR2, EGFR, ErbB2, PDGFR1, c-KIT and c-MET.
Expression levels of all these factors were significantly higher in tumour
samples than in normal mammary tissues taken from the same animal. Higher grading
was associated with higher VEGFR1 levels. Grade III tumours showed significantly
higher VEGF, c-MET and c-KIT mRNA expression, while Grade I tumours with lower
malignancy showed significantly higher PDGFR1 and EGFR expression than tumours
classified as Grade II or III. The increased presence of VEGF, VEGFR1, c-KIT and
c-MET is a negative prognostic factor as these signal transduction molecules
contribute to increased tumour malignancy. The presented data provide evidence,
for the first time, for the existence of a complex overexpression and
dysregulation of VEGF and several oncogenic tyrosine kinases such as VEGR1,
PDGFR1, c-KIT and c-MET in canine mammary tumours. Therefore, canine mammary
tumours may be potential targets for tyrosine kinase inhibitor therapy.
PMID- 29958528
TI - Glomerulosclerosis in transgenic rabbits with ubiquitous Venus protein
expression.
AB - Focal segmental glomerulosclerosis (FSGS) is a potential cause of nephrotic
syndrome both in humans and pet mammals. Glomerulopathy was reported earlier in
green fluorescent protein (GFP) transgenic (TG) mice, but glomerulosclerosis has
not been examined in GFP TG rabbits so far. In the present study, the potential
manifestation of FSGS was investigated in both Venus TG rabbits generated by
Sleeping Beauty (SB) transposition and age-matched control New Zealand White
(NZW) rabbits. Venus protein fluorescence was detected by confocal microscopy and
quantified by microplate reader. Urinalysis, haematology, serum biochemistry and
renal histology were performed to assess the signs of FSGS. Higher levels of
Venus fluorescence were determined in renal cortex samples than in the myocardium
by both methods. Urinalysis revealed proteinuria in Venus heterozygote TG bucks,
while Venus homozygote TG bucks developed microscopic haematuria. Supporting the
urinalysis data, the histological findings of FSGS (glomerulomegaly and sclerotic
glomeruli) were observed in renal cortex sections of Venus TG rabbits. Taken
together, Venus TG bucks were diagnosed with FSGS; thus, this type of
glomerulopathy could be a common disease in TG animals overexpressing GFP.
PMID- 29958530
TI - Anatomical and histological characteristics of the lungs in the ground squirrel
(Spermophilus citellus).
AB - The aim of this work was to study the topography, morphology, vascularisation,
histology and innervation of the lungs in the ground squirrel (Spermophilus
citellus) and compare these data with those concerning the rat, mole rat, rabbit
and mouse. The research was carried out on 15 animals. It was revealed that the
right lung has four lobes (cranial, middle, caudal and accessory lobes), while
the left lung is not divided into segments. The functional vessels are a.
pulmonalis dextra et sinistra and vv. pulmonales (5-6), while the nutritive
vessels of the lungs are a. bronchoesophagea dextra and v. bronchoesophagea
dextra. Histological tissue sections of the lungs revealed that the wall of
terminal bronchioles contains no cartilage and the mucosal epithelium is
pseudostratified, cubic and ciliated. Clara cells (club cells, bronchiolar
exocrine cells) are present but have no cilia. The lung alveolar diameter is 37
MUm on average, and the thickness of the alveolar wall and the interalveolar
septa is 1.38 MUm. Destruction of the alveolar walls, accumulation of
erythrocytes in the capillaries of alveolar septa and destruction of the
cytolemma of the capillary endothelium were detected. In addition, connective
tissue fibres and peripheral nerves were detected by silver impregnation.
PMID- 29958531
TI - Electroretinographic findings in day-blind dogs.
AB - Cone degeneration (cd; day blindness) is one of the inherited retinal diseases of
dogs. Its diagnosis is based on vision testing, fundoscopy, electroretinography
(ERG) and, for some breeds, on genetic tests. Typical signs of the disease are
day blindness and cone dysfunction during ERG while fundoscopy does not show any
abnormalities. The aim of this study was to compare behavioural findings,
fundoscopic lesions and electroretinographic alterations in 12 cd-affected dogs
(Alaskan Malamute, Labrador Retriever, German Shepherd, Dachshund, Yorkshire
Terrier, Shih Tzu, Siberian Husky and crossbreeds) examined at our clinic. None
of the examined dogs had any fundoscopic lesions, and all of them had normal
scotopic vision with strongly impaired or absent photopic vision. Light-adapted
transient, cone-mediated and steady-state, 31-Hz cone flicker ERGs were much
below the 5th percentile limits of normality or even unrecordable, while the rod
driven ERGs were within normal values. Vision test and ERG results corresponded
to each other and, combined with the results of fundoscopy, were typical of cd.
To date, our research is one of the few studies in the world presenting ERG
alterations compared with vision test findings and fundoscopic results in the
course of cd.
PMID- 29958532
TI - Frontal axial pattern flap combined with hard palate mucosa transplant in the
reconstruction of midfacial defects after the excision of huge basal cell
carcinoma.
AB - BACKGROUND: Our article describes our experience with using a frontal axial
pattern flap combined with hard palate mucosa transplant to reconstruct midfacial
defects after the excision of huge basal cell carcinoma. METHODS: We
retrospectively reviewed four patients diagnosed with midface huge basal cell
carcinoma through biopsy between 2014 and 2016. Both the eyelid and nose were
involved in all the patients. All the patients underwent the studied surgical
method and were followed up from 12 to 36 months. RESULTS: All the patients
preserved good eyelid function and relatively good esthetic satisfaction. No
basal cell carcinoma recurred. CONCLUSIONS: This combined surgical procedure is a
good method for reconstructing defects after the excision of huge basal cell
carcinomas in the midface.
PMID- 29958533
TI - A heterozygous variant in the SLC22A12 gene in a Sri Lanka family associated with
mild renal hypouricemia.
AB - BACKGROUND: Renal hypouricemia is a rare heterogeneous inherited disorder
characterized by impaired tubular uric acid transport, reabsorption insufficiency
and /or acceleration of secretion. The affected individuals are predisposed to
nephrolithiasis and recurrent episodes of exercise-induced acute kidney injury.
Type 1 is caused by dysfunctional variants in the SLC22A12 gene (URAT1), while
type 2 is caused by defects in the SLC2A9 gene (GLUT9). To date, more than 150
patients with the loss-of-function mutations for the SLC22A12 gene have been
found (compound heterozygotes and/or homozygotes), most of whom are Japanese and
Koreans. CASE PRESENTATION: Herein, we report a nine year old Sri Lankan boy with
renal hypouricemia (serum uric acid 97 MUmol/L, fractional excretion of uric acid
33%).The sequencing analysis of SLC22A12 revealed a potentially deleterious
missense variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state. This
variant has been previously identified in homozygous and/or compound heterozygous
state with other causative SLC22A12 variant c.1245_1253del (p.L415_G417del) in
Roma population. CONCLUSIONS: This is the first identification of a family with
mild renal hypouricemia1 associated to the p.T467 M variant. Detailed
investigations of urate blood and urine concentrations in patients with
unexplained hypouricemia are needed and renal hypouricemia should also be
considered in patients other than those from Japan and/or Korea. Our finding
confirms an uneven geographical and ethnic distribution of Romany prevalent
SLC22A12 variant that need to be considered in Asian patients (population data
Genome Aggregation Database: allele frequency in South Asia 0.007055, in East
Asia 0.001330).
PMID- 29958534
TI - Towards a public health approach for palliative care: an action-research study
focused on engaging a local community and educating teenagers.
AB - BACKGROUND: Education sessions about palliative care among teenagers are uncommon
in developed countries. However, very little is known either about the impact of
this type of intervention or about how this age-group perceives its impact. The
purpose of this study was therefore to (i) implement an education program about
palliative care among teenagers and (ii) to investigate the impact of the program
on the participants. METHODS: An action-research study was conducted at a local
community parish in Portugal in November 2015. An education programme was
purposively built about palliative care, using active educational strategies
adapted for teenagers. Quantitative and qualitative techniques and instruments
were used for data collection: questionnaire; reflective diaries; interviews and
written testimony. The program had three stages: preparation; intervention; and
evaluation. Qualitative data were analysed using thematic content analysis;
quantitative data were analysed descriptively. RESULTS: 69 people (47 teenagers)
participated in the education program. Findings show that the education program
contributed to creating awareness about palliative care. Both the teenagers and
other participants assessed the education program positively. At the end of the
program, teenagers had a constructive message about palliative care. CONCLUSIONS:
The education-intervention contributed to create awareness about palliative care
among the participant teenagers, who ended the program with a positive message
about palliative care. Based on our findings, the following policy implications
can be drawn: (1) Further research is needed to evaluate the effect of education
programs about palliative care among younger age groups (teenagers and children),
particularly in relation to the changing of attitudes toward palliative care. (2)
Education about palliative care should be promoted to local communities,
involving all age groups, to foster involvement, participation and empowerment.
(3) Compassionate communities should be promoted to enhance the health and
wellbeing of all citizens at the end of their life.
PMID- 29958535
TI - Avoiding Catch-22: validating the PainDETECT in a in a population of patients
with chronic pain.
AB - BACKGROUND: Neuropathic pain is defined as pain caused by a lesion or disease of
the somatosensory nervous system and is a major therapeutic challenge. Several
screening tools have been developed to help physicians detect patients with
neuropathic pain. These have typically been validated in populations pre
stratified for neuropathic pain, leading to a so called "Catch-22 situation:" "a
problematic situation for which the only solution is denied by a circumstance
inherent in the problem or by a rule". The validity of screening tools needs to
be proven in patients with pain who were not pre-stratified on basis of the
target outcome: neuropathic pain or non-neuropathic pain. This study aims to
assess the validity of the Dutch PainDETECT (PainDETECT-Dlv) in a large
population of patients with chronic pain. METHODS: A cross-sectional multicentre
design was used to assess PainDETECT-Dlv validity. Included where patients with
low back pain radiating into the leg(s), patients with neck-shoulder-arm pain and
patients with pain due to a suspected peripheral nerve damage. Patients' pain was
classified as having a neuropathic pain component (yes/no) by two experienced
physicians ("gold standard"). Physician opinion based on the Grading System was a
secondary comparison. RESULTS: In total, 291 patients were included. Primary
analysis was done on patients where both physicians agreed upon the pain
classification (n = 228). Compared to the physician's classification, PainDETECT
Dlv had a sensitivity of 80% and specificity of 55%, versus the Grading System it
achieved 74 and 46%. CONCLUSION: Despite its internal consistency and test-retest
reliability the PainDETECT-Dlv is not an effective screening tool for a
neuropathic pain component in a population of patients with chronic pain because
of its moderate sensitivity and low specificity. Moreover, the indiscriminate use
of the PainDETECT-Dlv as a surrogate for clinical assessment should be avoided in
daily clinical practice as well as in (clinical-) research. Catch-22 situations
in the validation of screening tools can be prevented by not pre-stratifying the
patients on basis of the target outcome before inclusion in a validation study
for screening instruments. TRIAL REGISTRATION: The protocol was registered
prospectively in the Dutch National Trial Register: NTR 3030 .
PMID- 29958536
TI - GrapHi-C: graph-based visualization of Hi-C datasets.
AB - OBJECTIVES: Hi-C is a proximity-based ligation reaction used to detect regions of
the genome that are close in 3D space (or "interacting"). Typically, results from
Hi-C experiments (contact maps) are visualized as heatmaps or Circos plots. While
informative, these visualizations do not directly represent genomic structure and
folding, making the interpretation of the underlying 3D genomic organization
obscured. Our objective was to generate a graph-based contact map representation
that leads to a more intuitive structural visualization. RESULTS: Normalized
contact maps were converted into undirected graphs where each vertex represented
a genomic region and each edge represented a detected (intra- and inter
chromosomal) or known (linear) interaction between two regions. Each edge was
weighted by the inverse of the linear distance (Hi-C experimental resolution) or
the interaction frequency from the contact map. Graphs were generated based on
this representation scheme for contact maps from existing fission yeast datasets.
Originally, these datasets were used to (1) identify specific principles
influencing fission yeast genome organization and (2) uncover changes in fission
yeast genome organization during the cell cycle. When compared to the equivalent
heatmaps and/or Circos plots, the graph-based visualizations more intuitively
depicted the changes in genome organization described in the original studies.
PMID- 29958538
TI - Cognition comes of age: comments on the new FDA draft guidance for early
Alzheimer's disease.
AB - BACKGROUND: The FDA have recently published draft guidance for the development of
treatments for early Alzheimer's disease. Key features of this guidance are the
advocacy of sensitive cognitive measures and a taxonomy of disease severity.
Whilst desirable patterns of cognitive-functional improvement are included,
specific measures, and the magnitude of required effects, are not described. MAIN
SECTION: We describe key elements of the guidance content, especially with regard
targeting key cognitive domains and the means by which they might be efficiently
indexed in the disease stages included in the guidance. We discuss also the
opportunities to assess cognitive performance in 'Stage 2' and 'Stage 3'
patients, as well as the possibilities for effectively assessing function in the
latter category. In this section we review candidate cognitive assessments that
we judge are capable of delivering on the guidance specification for sensitive
neuropsychological measures. This includes detailed consideration of the ADCS
PACC and Catch-Cog initiatives. With respect to the magnitude of effects, we
propose that standardised effect sizes of 0.3 represent a reasonable level of
efficacy based on the observation that already marketed drugs on average deliver
this level of improvement. CONCLUSIONS: We propose the use of cognitive measures
in stage 2 patients to index the cognitive skills known to be compromised early
in the Alzheimer's disease process. We recommend extending the traditional
interest in episodic memory to include sensitive, reliable and valid measures of
attention, working memory and aspects of executive function. We propose a focus
on these additional cognitive abilities based on evidence that performance on
tests of these domains is moderately well related to functional skills.
PMID- 29958537
TI - Correction to: First results on survival from a large Phase 3 clinical trial of
an autologous dendritic cell vaccine in newly diagnosed glioblastoma.
AB - Following publication of the original article [1], the authors reported an error
in the spelling of one of the author names. In this Correction the incorrect and
correct author names are indicated and the author name has been updated in the
original publication. The authors also reported an error in the Methods section
of the original article. In this Correction the incorrect and correct versions of
the affected sentence are indicated. The original article has not been updated
with regards to the error in the Methods section.
PMID- 29958539
TI - Consistent inverse correlation between DNA methylation of the first intron and
gene expression across tissues and species.
AB - BACKGROUND: DNA methylation is one of the main epigenetic mechanisms for the
regulation of gene expression in eukaryotes. In the standard model, methylation
in gene promoters has received the most attention since it is generally
associated with transcriptional silencing. Nevertheless, recent studies in human
tissues reveal that methylation of the region downstream of the transcription
start site is highly informative of gene expression. Also, in some cell types and
specific genes it has been found that methylation of the first intron, a gene
feature typically rich in enhancers, is linked with gene expression. However, a
genome-wide, tissue-independent, systematic comparative analysis of the
relationship between DNA methylation in the first intron and gene expression
across vertebrates has not been explored yet. RESULTS: The most important
findings of this study are: (1) using different tissues from a modern fish, we
show a clear genome-wide, tissue-independent quasi-linear inverse relationship
between DNA methylation of the first intron and gene expression. (2) This
relationship is conserved across vertebrates, since it is also present in the
genomes of a model pufferfish, a model frog and different human tissues. Among
the gene features, tissues and species interrogated, the first intron's negative
correlation with the gene expression was most consistent. (3) We identified more
tissue-specific differentially methylated regions (tDMRs) in the first intron
than in any other gene feature. These tDMRs have positive or negative correlation
with gene expression, indicative of distinct mechanisms of tissue-specific
regulation. (4) Lastly, we identified CpGs in transcription factor binding
motifs, enriched in the first intron, the methylation of which tended to increase
with the distance from the first exon-first intron boundary, with a concomitant
decrease in gene expression. CONCLUSIONS: Our integrative analysis clearly
reveals the important and conserved role of the methylation level of the first
intron and its inverse association with gene expression regardless of tissue and
species. These findings not only contribute to our basic understanding of the
epigenetic regulation of gene expression but also identify the first intron as an
informative gene feature regarding the relationship between DNA methylation and
gene expression where future studies should be focused.
PMID- 29958541
TI - Age-dependent difference in impact of fertility preserving surgery on disease
specific survival in women with stage I borderline ovarian tumors.
AB - BACKGROUND: This study was to determine age-specific impact of fertility
preserving surgery on disease-specific survival in women with stage I borderline
ovarian tumors (BOTs). Patients diagnosed during 1988-2000 were selected from The
Surveillance, Epidemiology, and End Results (SEER) database. The age-specific
impact of fertility preserving surgery and other risk factors were analyzed in
patients with stage I BOTs using Cox proportion hazard regression models. Data
from our hospital were collected during 1996-2017 to determine the prevalence of
patients who had undergone fertility preserving surgery. RESULTS: Of a total 6295
patients in the SEER database, this study selected 2946 patients with stage T1
BOTs who underwent fertility preserving or radical surgery. Their median age at
diagnosis was 45.0 years and the median follow-up time was 200 months. Fertility
preserving surgery was performed in 1000/1751 (57.1%) patients < 50 years and in
1,81/1195 (15.1%) patients >=50 years. Fertility preserving surgery was
significantly associated with worse disease-specific survival only in patients
>=50 years. Increased age, stage T1c and mucinous histology were risk factors for
overall patients or patients >=50 years, but not for < 50 years. Data from our
hospital showed that fertility preserving surgery was performed in 53.9 and
12.3%patients < 50 and >= 50 years with stage I disease, respectively.
CONCLUSION: Fertility preserving surgery is safe for women < 50 years with early
staged BOTs, but it may decrease disease-specific survival in patients >=50
years. Conservative surgery is performed at a relatively high rate in patients
>=50 years.
PMID- 29958542
TI - Effect of resveratrol and metformin on ovarian reserve and ultrastructure in
PCOS: an experimental study.
AB - BACKGROUND: PCOS is a reproductive hormonal abnormality and a metabolic disorder.
It is frequently associated with insulin resistance, hyperandrogenism, chronic
inflammation, and oxidative stress. We aim to investigate the potential
therapeutic effects of combined therapy of resveratrol and metformin on
polycystic ovaries via SIRT1 and AMPK activation. METHODS: Wistar albino rats
were divided into control and experimental (PCOS) groups. DHEA-induced PCOS rats
were given resveratrol (20 mg/kg/day), metformin (300 mg/kg/day) and combined
therapy. At the end of the experiment, the body and ovarian weight of rats were
measured and blood samples were analyzed for FSH, LH, testosterone, AMH, TNF
alpha and MDA levels. Histopathological evaluation of ovaries were carried out by
light and electron microscopy. SIRT1 and AMPK immunreactivity and TUNEL assay
were scored. Data were statistically analyzed by SPSS programme. RESULTS:
Metformin and combined treatment groups reduced the body and ovary weights
compared to the PCOS group. Serum testosterone levels were significantly higher
in the PCOS group than in the control group and this was reduced when PCOS was
treated with all but especially resveratrol. All the treatment groups decreased
LH, LH/FSH, TNF-alpha and tissue AMH levels which were induced in the PCOS group,
whereas metformin was unable to improve the increased MDA and plasma AMH levels.
Treatment with resveratrol and/or metformin ameliorated the elevated number of
secondary and atretic follicles and the decreased number of Graafian follicles in
the PCOS group, which indicates the effect of the treatments on the maintenance
of folliculogenesis. Light and electron microscopic findings supported the
analysis of follicular count. Increased number of TUNEL (+) granulosa cells in
the PCOS group were reduced significantly in the treatment groups. Resveratrol
and metformin increased SIRT1 and AMPK immunreactivity, respectively, compared to
the PCOS group. CONCLUSIONS: The results suggest that combined therapy of
metformin and resveratrol may improve the weight gain, hormone profile and
ovarian follicular cell architecture by inducing antioxidant and antiinflammatory
systems via SIRT1 and AMPK activation in PCOS.
PMID- 29958540
TI - Postnatal developmental dynamics of cell type specification genes in Brn3a/Pou4f1
Retinal Ganglion Cells.
AB - BACKGROUND: About 20-30 distinct Retinal Ganglion Cell (RGC) types transmit
visual information from the retina to the brain. The developmental mechanisms by
which RGCs are specified are still largely unknown. Brn3a is a member of the
Brn3/Pou4f transcription factor family, which contains key regulators of RGC
postmitotic specification. In particular, Brn3a ablation results in the loss of
RGCs with small, thick and dense dendritic arbors ('midget-like' RGCs), and
morphological changes in other RGC subpopulations. To identify downstream
molecular mechanisms underlying Brn3a effects on RGC numbers and morphology, our
group recently performed a RNA deep sequencing screen for Brn3a transcriptional
targets in mouse RGCs and identified 180 candidate transcripts. METHODS: We now
focus on a subset of 28 candidate genes encoding potential cell type determinant
proteins. We validate and further define their retinal expression profile at five
postnatal developmental time points between birth and adult stage, using in situ
hybridization (ISH), RT-PCR and fluorescent immunodetection (IIF). RESULTS: We
find that a majority of candidate genes are enriched in the ganglion cell layer
during early stages of postnatal development, but dynamically change their
expression profile. We also document transcript-specific expression differences
for two example candidates, using RT-PCR and ISH. Brn3a dependency could be
confirmed by ISH and IIF only for a fraction of our candidates. CONCLUSIONS:
Amongst our candidate Brn3a target genes, a majority demonstrated ganglion cell
layer specificity, however only around two thirds showed Brn3a dependency. Some
were previously implicated in RGC type specification, while others have known
physiological functions in RGCs. Only three genes were found to be consistently
regulated by Brn3a throughout postnatal retina development - Mapk10, Tusc5 and
Cdh4.
PMID- 29958543
TI - Synthetic DNA fragments bearing ICR cis elements become differentially methylated
and recapitulate genomic imprinting in transgenic mice.
AB - BACKGROUND: Genomic imprinting is governed by allele-specific DNA methylation at
imprinting control regions (ICRs), and the mechanism controlling its differential
methylation establishment during gametogenesis has been a subject of intensive
research interest. However, recent studies have reported that gamete methylation
is not restricted at the ICRs, thus highlighting the significance of ICR
methylation maintenance during the preimplantation period where genome-wide
epigenetic reprogramming takes place. Using transgenic mice (TgM), we previously
demonstrated that the H19 ICR possesses autonomous activity to acquire paternal
allele-specific DNA methylation after fertilization. Furthermore, this activity
is indispensable for the maintenance of imprinted methylation at the endogenous
H19 ICR during the preimplantation period. In addition, we showed that a specific
5' fragment of the H19 ICR is required for its paternal methylation after
fertilization, while CTCF and Sox-Oct motifs are essential for its maternal
protection from undesirable methylation after implantation. RESULTS: To ask
whether specific cis elements are sufficient to reconstitute imprinted
methylation status, we employed a TgM co-placement strategy for facilitating
detection of postfertilization methylation activity and precise comparison of
test sequences. Bacteriophage lambda DNA becomes highly methylated regardless of
its parental origin and thus can be used as a neutral sequence bearing no
inclination for differential DNA methylation. We previously showed that insertion
of only CTCF and Sox-Oct binding motifs from the H19 ICR into a lambda DNA (LCb)
decreased its methylation level after both paternal and maternal transmission. We
therefore appended a 478-bp 5' sequence from the H19 ICR into the LCb fragment
and found that it acquired paternal-allele-specific methylation, the dynamics of
which was identical to that of the H19 ICR, in TgM. Crucially, transgene
expression also became imprinted. Although there are potential binding sites for
ZFP57 (a candidate protein thought to control the methylation imprint) in the
larger H19 ICR, they are not found in the 478-bp fragment, rendering the role of
ZFP57 in postfertilization H19 ICR methylation a still open question.
CONCLUSIONS: Our results demonstrate that a differentially methylated region can
be reconstituted by combining the activities of specific imprinting elements and
that these elements together determine the activity of a genomically imprinted
region in vivo.
PMID- 29958544
TI - Phosphorylation of different tau sites during progression of Alzheimer's disease.
AB - Alzheimer's disease is characterized by accumulation of amyloid plaques and tau
aggregates in several cortical brain regions. Tau phosphorylation causes
formation of neurofibrillary tangles and neuropil threads. Phosphorylation at tau
Ser202/Thr205 is well characterized since labeling of this site is used to assign
Braak stage based on occurrence of neurofibrillary tangles. Only little is known
about the spatial and temporal phosphorylation profile of other phosphorylated
tau (ptau) sites. Here, we investigate total tau and ptau at residues Tyr18,
Ser199, Ser202/Thr205, Thr231, Ser262, Ser396, Ser422 as well as amyloid-beta
plaques in human brain tissue of AD patients and controls. Allo- and isocortical
brain regions were evaluated applying rater-independent automated quantification
based on digital image analysis. We found that the level of ptau at several
residues, like Ser199, Ser202/Thr205, and Ser422 was similar in healthy controls
and Braak stages I to IV but was increased in Braak stage V/VI throughout the
entire isocortex and transentorhinal cortex. Quantification of ThioS-stained
plaques showed a similar pattern. Only tau phosphorylation at Tyr18 and Thr231
was already significantly increased in the transentorhinal region at Braak stage
III/IV and hence showed a progressive increase with increasing Braak stages.
Additionally, the increase in phosphorylation relative to controls was highest at
Tyr18, Thr231 and Ser199. By contrast, Ser396 tau and Ser262 tau showed only a
weak phosphorylation in all analyzed brain regions and only minor progression.
Our results suggest that the ptau burden in the isocortex is comparable between
all analyzed ptau sites when using a quantitative approach while levels of ptau
at Tyr18 or Thr231 in the transentorhinal region are different between all Braak
stages. Hence these sites could be crucial in the pathogenesis of AD already at
early stages and therefore represent putative novel therapeutic targets.
PMID- 29958548
TI - Silver Nanoparticles for Enhanced Cancer Theranostics: In Vitro and In Vivo
Perspectives.
AB - Silver nanoparticles (AgNPs) have attracted great attention in cancer
theranostics due to their extraordinary physiochemical and biological properties.
This review discusses a large number of papers and summarizes the recent
applications of AgNPs in cancer theranostics from the following five
perspectives: (1) desirable features of AgNPs for theranostic applications, (2)
synthesis of AgNPs by physical, chemical, and biological processes, (3)
applications of AgNPs in cancer theranostics in vitro, (4) applications of AgNPs
in cancer theranostics in vivo, and (5) nanotoxicity of AgNPs. Furthermore, some
views are discussed that concern the synthetic challenges, toxicity, and clinical
translation of AgNPs and the future development of multifunctional theranostic
platforms. Overall, the historical developments and recent applications of AgNPs
confirm their important role in the cancer field. It is strongly believed that
AgNPs will open a new route toward cancer theranostics in the near future.
PMID- 29958545
TI - Biological effects of radiation on cancer cells.
AB - With the development of radiotherapeutic oncology, computer technology and
medical imaging technology, radiation therapy has made great progress. Research
on the impact and the specific mechanism of radiation on tumors has become a
central topic in cancer therapy. According to the traditional view, radiation can
directly affect the structure of the DNA double helix, which in turn activates
DNA damage sensors to induce apoptosis, necrosis, and aging or affects normal
mitosis events and ultimately rewires various biological characteristics of
neoplasm cells. In addition, irradiation damages subcellular structures, such as
the cytoplasmic membrane, endoplasmic reticulum, ribosome, mitochondria, and
lysosome of cancer cells to regulate various biological activities of tumor
cells. Recent studies have shown that radiation can also change the tumor cell
phenotype, immunogenicity and microenvironment, thereby globally altering the
biological behavior of cancer cells. In this review, we focus on the effects of
therapeutic radiation on the biological features of tumor cells to provide a
theoretical basis for combinational therapy and inaugurate a new era in oncology.
PMID- 29958547
TI - Agenesis of dorsal pancreas associated with pancreatic neuroendocrine tumor: a
case report and review of the literature.
AB - BACKGROUND: Agenesis of the dorsal pancreas is very rare. Less than 70 cases have
been reported to date. Some of these cases had an association with a tumor. The
literature of agenesis of the dorsal pancreas and agenesis of the dorsal pancreas
associated pancreatic neoplasia is limited. Here we report the second case of a
pancreatic neuroendocrine tumor in a setting of agenesis of the dorsal pancreas.
CASE PRESENTATION: A 71-year-old man, originally from North Africa, with a
history of insulin-dependent diabetes mellitus, presented with a 2-month history
of nonspecific abdominal symptoms. Contrast-enhanced computed tomography
demonstrated an almost 3 cm round, quite well-defined and homogeneous tumor
formation in the area between the neck and absent body and tail of his pancreas.
The mass was confirmed by endoscopic ultrasound. Our patient underwent computed
tomography-guided biopsy of the mass which provided proof of a neuroendocrine
tumor. He underwent pancreas resection because of the presence of a
neuroendocrine tumor. Seven months later his glycated hemoglobin increased from
6.9 to 8.7%. CONCLUSIONS: Diagnosis of agenesis of the dorsal pancreas is based
on imaging techniques like computed tomography, magnetic resonance
cholangiopancreatography, or endoscopic ultrasound. Endoscopic ultrasound-guided
fine-needle aspiration can be helpful for the histological diagnosis of the
tumor. The hypothesis of the association between pancreatic neoplasia and
agenesis of the dorsal pancreas leads us to the suggestion that every patient
with diagnosed agenesis of the dorsal pancreas should be observed with a focus on
the early detection of potential malignancy.
PMID- 29958549
TI - Fluorescent Lignin Carbon Dots for Reversible Responses to High-Valence Metal
Ions and Its Bioapplications.
AB - A sensitive and reversible sensing platform based on fluorescent carbon dots
(CDs) allowing capture and detection of metal ions is of significance for
developing diagnostic probes and in-situ environmental-monitoring. Here, a simple
and effective method for converting biomass lignin into fluorescent CDs is
developed. The obtained CDs, with stable fluorescence and excellent water
solubility, are fabricated as unique model biosensors to access the metal-induced
quenching mechanism. It is demonstrated that selective fluorescence quenching
behaviors of lignin CDs are firstly found related to the valence-state of metal
ions. Moreover, a reversible control of CDs fluorescence is realized by
introducing reducing agents. This novel biosensor and the approach to quenching
mechanism may evoke new insight in designing ions-sensor and monitoring biologic
redox signal.
PMID- 29958550
TI - Effects of Wallpaper with the Ability of Photo-Activated Releasing Fragrance on
Central Nervous System.
AB - Fragrances can relax us and bring a good spirit for us. But they cannot produce
these results or produce the opposite results if the concentrations of fragrances
in the air are large due to their strong volatility. To overcome this obstacle,
mesoporous silica nanospheres with the ability of photo-activated releasing
sandela 803 (MS-S@S803) were prepared. And the effects and internal mechanism of
MS-S-W@S803 on CNS were study from behavioural level, tissue level, cell level
and molecule level. MS-S-W@S803 could relieve the stress and beat the anxiety.
Besides, it could also stimulate the neural activity of hippocampus, hypothalamus
and olfactory bulb regions at a higher intensity. In addition, the abilities of
nerve regenerations in corpus striatum, substantia nigra and olfactory bulb were
increased by MS-S-W@S803. And the expressions of DOPA, Ach, GABA and NMDA were
also facilitated by MS-S-W@S803. Interestingly, the anxiolytic effects were more
significant as time progresses.
PMID- 29958546
TI - Neuroimaging-pathological correlations of [18F]THK5351 PET in progressive
supranuclear palsy.
AB - Recent positron emission tomography (PET) studies have demonstrated the
accumulation of tau PET tracer in the affected region of progressive supranuclear
palsy (PSP) cases. To confirm the binding target of radiotracer in PSP, we
performed an imaging-pathology correlation study in two autopsy-confirmed PSP
patients who underwent [18F]THK5351 PET before death. One patient with PSP
Richardson syndrome showed elevated tracer retention in the globus pallidus and
midbrain. In a patient with PSP-progressive nonfluent aphasia, [18F]THK5351
retention also was observed in the cortical areas, particularly the temporal
cortex. Neuropathological examination confirmed PSP in both patients. Regional
[18F]THK5351 standardized uptake value ratio (SUVR) in antemortem PET was
significantly correlated with monoamine oxidase-B (MAO-B) level, reactive
astrocytes density, and tau pathology at postmortem examination. In in vitro
autoradiography, specific THK5351 binding was detected in the area of antemortem
[18F]THK5351 retention, and binding was blocked completely by a reversible
selective MAO-B inhibitor, lazabemide, in brain samples from these patients. In
conclusion, [18F]THK5351 PET signals reflect MAO-B expressing reactive
astrocytes, which may be associated with tau accumulation in PSP.
PMID- 29958551
TI - Synthesis, Characterization and In Vitro Evaluation of Dual pH/Redox Sensitive
Marine Laminarin-Based Nanomedicine Carrier Biomaterial for Cancer Therapy.
AB - In order to improve the anti-cancer therapy efficiency of hydrophobic drugs such
as curcumin (Cur), a novel dual pH/redox sensitive marine laminarin-based
nanomedicine carrier biomaterial with photo-dynamic therapy (PDT) was synthesized
in this study. The new synthetic chemical structure, named as Hematin-Laminarin
Dithiodipropionic Acid-MGK (HLDM), was characterized by 1H-NMR and IR. The Cur
loaded micelles were then prepared via dialysis method. The HLDM could self
assemble into micelles in water with hydrodynamic diameter of 135+/-15 nm. The
particle size, zeta potential and morphology of micelles were detected by
transmission electron microscope (TEM). Interestingly, the in vitro release
experiment showed that the release amount of Cur-loaded HLDM micelles could reach
80% in the pH and redox sensitive environment. Furthermore, cell study showed
that the Cur-loaded HLDM micelles had stronger cellular uptake and cytotoxicity
to MCF-7 cells than that of HLDM. The multifunctional marine laminarin based
nanomedicine carrier biomaterial can be used for new drug delivery systems with
dual pH/redox sensitivity for cancer therapy.
PMID- 29958552
TI - Effects of Fragrance-Loaded Mesoporous Silica Nanocolumns on Central Nervous
System.
AB - Fragrances have rapid effect on our central nervous system, such as making the
spirit of relaxation, relieving tensions and refreshing ourselves. However, the
release of fragrances is not stable. Here, we added photo-driven mesoporous
silica nanocolumns loaded with sandela 803 (MS-C@S803) into wallpaper to obtain
fragrant wallpaper (MS-C-W@S803). We then analysed the effects of MS-C-W@S803 and
pure sandela 803 treated wallpaper (W@S803) on the CNS of mice and explored the
internal mechanism of these effects. Besides, we evaluated the short-term (7
days) and long-term (30 days) effects of the fragrance treated wallpaper. In
behaviouristics level, we detected the anxiolytic effects via elevated plus maze
and open field test. In tissue level, we analysed the neural activity in
hippocampus, hypothalamus and olfactory bulb regions via measuring the
electrophysiological signal. In cell level, we tested the nerve regeneration in
hippocampus, substantia nigra and corpus striatum via immunofluorescence staining
with the anti-BrdU antibody. In molecule level, we measured the expression of
dopamine, acetylcholine, gamma-aminobutyric acid (GABA) and N-methyl-D-aspartic
acid (NMDA) via liquid chromatography-mass spectrometry. Finally, we find that MS
C-W@S803 had anxiolytic effects on the CNS of mice, and the effects were more
significant as time progresses.
PMID- 29958553
TI - Multidimensional Theranostics for Tumor Fluorescence Imaging, Photoacoustic
Imaging and Photothermal Treatment Based on Manganese Doped Carbon Dots.
AB - Multidimensional theranostics have received a lot of attention because of their
improved diagnostic accuracy and therapeutic diversity. In this study, we
developed a kind of manganese doped nigrosine originated carbon dots (Mn-NCDs),
with the average particle size of approximate 3 nm and the long emission
wavelength of 653 nm. In vitro experiment demonstrated that Mn-NCDs could be well
internalized by 4T1 cells, and the temperature of Mn-NCDs solution could rapidly
rise from 23.1 degrees C to more than 50 degrees C when exposed to NIR laser,
thus it could generate enough hyperthermia to efficiently destroy 4T1 cells.
Furthermore, the in vivo fluorescent and photoacoustic imaging studies
highlighted the applicability of Mn-NCDs in dual-mode tumor diagnosis. The
prepared Mn-NCDs with long emission wavelength and photothermal anti-cancer
effect exhibited great potential for dual-mode imaging and treatment of triple
negative breast cancer.
PMID- 29958554
TI - Ascorbic Palmitate as a Bifunctional Drug and Nanocarrier of Paclitaxel for
Synergistic Anti-Tumor Therapy.
AB - The in vivo application of ascorbate is currently limited by the very high blood
concentrations that are required to achieve therapeutic levels in tumors, which
needs to exploit a novel drug platform to improve the pharmacokinetics of vitamin
C (Vc) and its antitumoral effects. In this study, ascorbyl palmitate (AP), an
amphiphilic molecule, is the palmitate acid ester derivative of ascorbic acid,
which can be formed a "bifunctional" nanoparticle in which the AP acts not only
as an antitumor drug but also as a nanocarrier for encapsulating hydrophobic
antitumor drugs such as paclitaxel (PTX). We developed a bifunctional nanocarrier
based on AP, which loaded with PTX for synergistic cancer chemotherapy. The
resulting PTX-AP nanoparticles (PTX-APNPs) were spherical and had an average size
of 294.2 nm based on dynamic light scattering. The in vitro anti-B16F10 cells
test of PTX-APNPs revealed an obvious synergistic effect of AP and PTX, and the
PTX-APNPs strongly induced cell apoptosis and production of reactive oxygen
species. In addition, PTX-APNPs formulation also effectively suppressed the
tumorigenicity of B16F10 cells in female C57BL/6 mice without causing severe
toxicity. These results suggest that AP-based nanoparticles formulated with
paclitaxel are useful for synergistic chemotherapy.
PMID- 29958555
TI - Functionalized Multi-Walled Carbon Nanotubes for Targeting Delivery of
Immunostimulatory CpG Oligonucleotides Against Prostate Cancer.
AB - Immuno-based oncotherapy has been successfully implemented for cancer treatment.
In the present study, we developed a Oligodeoxynucleotides (ODNs) containing
unmethylated CpG motifs (CpG ODNs) nano-delivery system based on Multi-walled
carbon nanotubes (MWCNTs) conjugated with H3R6 polypeptide (MHR-CpG) for prostate
cancer immunotherapy. The in vitro and in vivo toxicity data revealed that the
prepared MHR showed high biocompatibility. Confocal laser scanning microscopy
confirmed that MHR-CpG could specifically target the endosomal TLR9. In addition,
the use of MHR enhanced the immunogenicity of CpG in both humoral and cellular
immune pathways, as evidenced by the increased expression of CD4+ T-cells, CD8+ T
cells, TNF-alpha, and IL-6. The in vivo anti-cancer efficacy study on RM-1 tumor
bearing mice demonstrated that MHR-CpG could deliver the immunotherapeutics to
the tumor site and the tumor-draining lymph node to suppress tumor growth. These
results suggested that MHR-CpG was a promising multifunctional nano system for
prostate cancer immunotherapy.
PMID- 29958556
TI - Nitrogen-Incorporated Ultrananocrystalline Diamond Electrodes for Dopamine
Determination.
AB - In this paper, nitrogen incorporated ultrananocrystalline diamond (NUNCD) films
were fabricated for use as electrodes to detect dopamine. The NUNCD electrodes
achieved high sensitivity, great selectivity, and excellent detection limits for
dopamine sensing. The NUNCD electrode, fabricated as a potential sensitive
biosensor for dopamine without any catalyst or mediators, demonstrated good
activity for the direct detection of dopamine by simply putting the bare NUNCD
electrode into a dopamine solution. Furthermore, the marked selectivity of the
NUNCD electrode is very favorable for the determination of dopamine (DA)
concentration (0.32 MUM) in the presence of ascorbic acid (AA) and uric acid
(UA). Considering dopamine detection in real biological fluid samples, the NUNCD
electrode performed excellently with a detection limit of 0.39 MUM and a high
recovery ranging from 90-120%, revealing that NUNCD electrodes have promising use
in the sensing of dopamine.
PMID- 29958557
TI - Novel Carbon Dots Derived from Cirsii Japonici Herba Carbonisata and Their
Haemostatic Effect.
AB - The purpose of this study was to explore the haemostatic effect of novel carbon
dots (CDs) derived from Cirsii Japonici Herba Carbonisata (CJHC). Transmission
electron microscopy (TEM), high-resolution TEM, Fourier transform infrared
spectroscopy, ultraviolet-visible spectroscopy, fluorescence spectroscopy, X-ray
photoelectron spectroscopy, high performance liquid chromatography and a cell
counting kit-8 assay of CJHC-CDs were performed. Then the haemostatic effect of
this CJHC-CDs was studied in bleeding mouse models. To explore their related
haemostatic mechanism, coagulation parameters and platelets (PLT) were measured.
The CJHC-CDs ranged in diameter from 2 to 11 nm and had a quantum yield of 0.63%.
They exhibited no toxicity up to concentrations of 5752 MUg/mL. After
administration, mice had a significantly shortened bleeding time and the
coagulation parameters and PLT significantly increased. These results showed the
definite haemostatic effect of CJHC-CDs.
PMID- 29958558
TI - TLS11a Aptamer/CD3 Antibody Anti-Tumor System for Liver Cancer.
AB - New therapeutic approaches are needed for hepatocellular carcinoma (HCC), which
is the most common primary malignancy of the liver. Bispecific T-cell engagers
(BiTE) can effectively redirect T cells against tumors and show a strong anti
tumor effect. However, the potential immunogenicity, complexity, and high cost
significantly limit their clinical application. In this paper, we used the
hepatoma cells-specific aptamer TLS11a and anti-CD3 for to establish an
aptamer/antibody bispecific system (AAbs), TLS11a/CD3, which showed advantages
over BiTE and can specifically redirect T cells to lyse tumor cells. TLS11a-SH
and anti-CD3-NH2 were crosslinked with sulfosuccinimidyl 4-(N-maleimidomethyl)
cyclohexane-1-carboxylate (sulfo-SMCC). T cell activation, proliferation, and
cytotoxicity of TLS11a/CD3 were analyzed by flow cytometry. Cytokine array was
used to detect cytokine released from activated T cells. Hepatoma xenograft model
was used to monitor the tumor volume and survival. TLS11a/CD3 could specifically
bind hepatoma cells (H22) and T cells, activated T cells to mediate antigen
specific lysis of H22 cells in vitro, and effectively inhibited the growth of
implanted H22 tumors as well as prolonged mice survival. TLS11a/CD3 could
simultaneously target hepatoma cells and T cells, specifically guide T cells to
kill tumor cells, and enhance the anti-tumor effect of T cells both in vitro and
in vivo.
PMID- 29958559
TI - Transfection of Difficult-to-Transfect Rat Primary Cortical Neurons with Magnetic
Nanoparticles.
AB - The efficient cell transfection method is vital for various biomedical
applications, such as the CRISPR-Cas9 technique. Current cell transfection
methods, including lipofectamine, calcium phosphate co-precipitation,
nucleofection, and viral infection are not equally efficient for various cells
and have their disadvantages. In this study, a magnetic nanoparticle (MNP)-based
method was introduced for delivering both FITC dye and a functional EGFP gene
into easy-to-transfect HEK cells and difficult-to-transfect rat primary cortical
neurons. The transfection efficacy could be controlled in both time-dependent and
magnetic strength-dependent manner. This cell transfection method could have
substantial potential for targeted drug delivery.
PMID- 29958560
TI - Immunosuppressive Effect of Ticagrelor on Dendritic Cell Function: A New
Therapeutic Target of Antiplatelet Agents in Cardiovascular Disease.
AB - Atherosclerosis is being thought of as an autoimmune disease. As the most potent
antigen-presenting cells, dendritic cells (DCs) have been regarded as a major
target for the control of this harmful immune response. In this study, we
investigated the effect of ticagrelor, a new antiplatelet drug antagonizing the
P2Y12 receptor, on the function of mouse bone marrow-derived DCs. RT-PCR revealed
relatively high P2Y12 mRNA levels in DCs, and expression of the P2Y12 protein was
documented by western blot analysis. Moreover, antigen (Ag) uptake by DCs was
markedly increased following activation of the P2Y12 receptor by adenosine-5'-O
(2-thiodiphosphate) (ADPbetaS). Ticagrelor reduced the ADPbetaS-stimulated uptake
of fluorescein-labeled dextran by DCs while exerting no significant effect on
spontaneous endocytosis. In addition, ticagrelor suppressed the capacity of
ADPbetaS-stimulated DCs to induce activation of T lymphocytes. Ticagrelor blocked
the activation of phosphatidylinositol 3-kinase (PI3K) and extracellular signal
regulated kinase 1/2 (ERK1/2) in ADPbetaS-treated DCs. Preventing the activation
of PI3K reduced significantly ADPbetaS-induced endocytosis by DCs. Thus,
ticagrelor decreases Ag uptake by DCs via the inhibition of P2Y12 receptor
mediated PI3K activity, attenuating the stimulation of Ag-specific T cells. Our
findings indicate that ticagrelor may directly target DCs and inhibit their
function, suggesting a possible explanation for the immunoregulatory activity of
this drug.
PMID- 29958561
TI - Sickle cell disease-Unanswered questions and future directions in therapy.
PMID- 29958563
TI - Genetic therapies for sickle cell disease.
AB - After decades with few novel therapeutic options for sickle cell disease (SCD),
autologous hematopoietic stem cell (HSC) based genetic therapies including
lentiviral gene therapy (GT), and genome editing (GE) now appear imminent.
Lentiviral GT has advanced considerably in the past decade with promising
clinical trial results in multiple disorders. For beta-hemoglobinopathies, GT
strategies of gene addition and fetal hemoglobin induction through BCL11A
regulation are both being evaluated in open clinical trials. GE techniques offer
the possibility of a nonviral curative approach, either through sickle hemoglobin
mutation repair or fetal hemoglobin elevation. Although GE currently remains at
the preclinical stage, multiple clinical trials will likely open soon. In
addition to reviewing current strategies for GT and GE, this review highlights
important next steps toward optimization of these therapies. All autologous cell
based genetic therapies rely on safely obtaining an adequate yield of autologous
HSCs for genetic modification and transplantation. HSC collection is uniquely
challenging in SCD. Peripheral mobilization with plerixafor has recently emerged
as a promising approach. The acute and long-term toxicities associated with
myeloablative conditioning are risks that may not be acceptable to a significant
number of SCD patients, highlighting the need for novel conditioning regimens.
Finally, increasing availability of autologous genetic therapies will require
comprehensive and collaborative discussions regarding cost and access for SCD
patients, at individual centers and worldwide.
PMID- 29958562
TI - Fetal Hemoglobin Induction by Epigenetic Drugs.
AB - Fetal hemoglobin (HbF) inhibits the root cause of sickle pathophysiology, sickle
hemoglobin polymerization. Individuals who naturally express high levels of HbF
beyond infancy thus receive some protection from sickle complications. To mimic
this natural genetic experiment using drugs, one guiding observation was that HbF
is increased during recovery of bone marrow from extreme stress. This led to
evaluation and approval of the cytotoxic (cell killing) drug hydroxyurea to treat
sickle cell disease. Cytotoxic approaches are limited in potency and
sustainability, however, since they require hematopoietic reserves sufficient to
repeatedly mount recoveries from stress that destroys their counterparts, and
such reserves are finite. HbF induction even by stress ultimately involves
chromatin remodeling of the gene for HbF (HBG), therefore, a logical alternative
approach is to directly inhibit epigenetic enzymes that repress HBG-implicated
enzymes include DNA methyltransferase 1, histone deacetylases, lysine demethylase
1, protein arginine methyltransferase 5, euchromatic histone lysine
methyltransferase 2 and chromodomain helicase DNA-binding protein 4. Clinical
proof-of-principle that this alternative, noncytotoxic approach can generate
substantial HbF and total hemoglobin increases has already been generated. Thus,
with continued careful attention to fundamental biological and pharmacologic
considerations (reviewed herein), there is potential that rational, molecular
targeted, safe and highly potent disease-modifying therapy can be realized for
patients with sickle cell disease, with the accessibility and cost-effective
properties needed for world-wide effect.
PMID- 29958564
TI - Curative therapies: Allogeneic hematopoietic cell transplantation from matched
related donors using myeloablative, reduced intensity, and nonmyeloablative
conditioning in sickle cell disease.
AB - Sickle cell disease (SCD) chronically damages multiple organs over the lifetime
of affected individuals. Allogeneic hematopoietic cell transplantation (allo-HCT)
is the most studied curative intervention. Fully matched related marrow,
peripheral blood derived, or cord blood HCT have the best transplant outcome for
symptomatic patients with SCD. For patients with asymptomatic or milder disease
who have this donor option available, risks and benefits of HCT should be
discussed among the patient, family, treating hematologist, and transplant
physician, and decision to proceed to HCT should be individualized. Myeloablative
conditioning with busulfan, cyclophosphamide, and ATG has been a commonly
employed regimen for children and young adults. Recently, low intensity
conditioning with low dose total body irradiation and alemtuzumab is emerging as
an efficacious and safe regimen for adults, young adults, and possibly children.
Mixed donor chimerism (minimum >=20% myeloid cells), from myeloablative or
nonmyeloablative conditioning regimen, produces robust normal donor
erythropoiesis and is sufficient to provide a clinical cure. The proportion of
patients remaining on immunosuppression beyond 2 years post-HCT is likely <10%
with either myeloablative or low intensity regimens. Late effects from
myeloablative or reduced intensity conditioning, or from several more months of
immunosuppression in low intensity conditioning may be less common than those
observed in HCT for malignant indications. Nonmyeloablative approaches with low
toxicities should be the focus of future research efforts. Prevention of GVHD is
a shared goal in all approaches of allo-HCT in SCD.
PMID- 29958565
TI - When there is no match, the game is not over: Alternative donor options for
hematopoietic stem cell transplantation in sickle cell disease.
AB - Many patients with sickle cell disease experience severe morbidity and early
mortality. The only curative option remains hematopoietic stem cell
transplantation. Although HLA-matched sibling transplantation has been very
successful for adults and children, the vast majority of patients with sickle
cell disease do not have an HLA-matched sibling. Alternative donor options
include haploidentical, unrelated umbilical cord blood, and matched unrelated
donor transplantation. This report summarizes major alternative donor
transplantation studies reported to date and ongoing and upcoming clinical
trials. We conclude that when there is no HLA-match, all these approaches should
be systematically considered before ruling out the option of hematopoietic stem
cell transplantation.
PMID- 29958566
TI - A new option for treating CKD-associated anaemia in children.
PMID- 29958567
TI - The real world of Waldenstrom's macroglobulinaemia.
PMID- 29958569
TI - Treatment and outcome patterns in European patients with Waldenstrom's
macroglobulinaemia: a large, observational, retrospective chart review.
AB - BACKGROUND: Treatment options for Waldenstrom's macroglobulinaemia are
heterogeneous, and no well established treatment standards exist. Although
guidelines from the Eighth International Workshop on Waldenstrom's
Macroglobulinemia were published in 2016, inconsistent awareness and budget
constraints have prevented their widespread implementation, and real-life
treatment patterns might differ across health-care systems. We aimed to generate
information about treatment and outcome patterns for patients with Waldenstrom's
macroglobulinaemia outside of clinical trials. METHODS: In this large,
observational, retrospective chart review, academic and community physicians in
ten European countries were invited to retrospectively complete electronic
records for patients with symptomatic Waldenstrom's macroglobulinaemia who had
begun treatment after Jan 1, 2000, and before Jan 1, 2014, and had available
clinical and biological data. The primary endpoints were reasons for treatment
initiation, treatment choices, progression-free survival, and overall survival.
We assessed the variables that affected choice of front-line therapy, progression
free survival, and overall survival in multivariate analyses. FINDINGS:
Electronic records were reviewed for 454 eligible patients. The most frequent
reasons for starting front-line treatment were anaemia (in 328 [72%] patients)
and constitutional symptoms (in 264 [58%] patients). Choice of therapy varied
between front-line, second-line, and third-line approaches; age; and type of
institution. In the front-line setting, 193 (43%) of 454 patients received
monotherapy, 164 (36%) received chemoimmunotherapy, and 95 (21%) received other
combination regimens (data on front-line treatment were missing for one patient,
and another patient received only steroids). After front-line treatment, median
progression-free survival was 29 months (95% CI 25-31), median overall survival
was not reached (not reached-not reached), and 10-year overall survival was 69%
(62-74). In multivariate analyses, patients who were high risk according to the
International Prognostic Scoring System for Waldenstrom Macroglobulinemia had
significantly worse progression-free survival and overall survival than did those
who were low risk. Additionally, progression-free survival was shortened in
patients treated with monotherapy compared with those treated with
chemoimmunotherapy or other combination therapies and in those treated at an
academic institution compared with those treated in the community. Constitutional
symptoms (excluding fatigue) were associated with worsened overall survival.
INTERPRETATION: This large observational dataset should inform and help set
guidelines, and improve understanding of treatment practices and outcomes, for
European patients with Waldenstrom's macroglobulinaemia. FUNDING: Pharmacyclics
LLC (an AbbVie company).
PMID- 29958571
TI - Corrigendum.
PMID- 29958570
TI - Intravenous iron sucrose versus oral iron administration for the postoperative
treatment of post-bariatric abdominoplasty anaemia: an open-label, randomised,
superiority trial in Brazil.
AB - BACKGROUND: Anaemia and iron deficiency are common after post-bariatric
abdominoplasty, which can involve removal of large areas of skin with associated
blood loss. Because the oral absorbability of iron is reduced after bariatric
surgery (through reduced intake, reduction of gastric acid secretion for
conjugation of iron, and separation of the iron-absorptive areas of the duodenum
and jejunum), it has been hypothesised that postoperative intravenous iron
supplementation might be used to treat anaemia and iron deficiency in patients
submitted to post-bariatric plastic surgeries. We aimed to assess whether
intravenous iron administered postoperatively in post-bariatric abdominoplasty
could result in increased blood haemoglobin concentrations compared with oral
iron supplementation. METHODS: In this open-label, randomised, superiority trial,
we recruited women aged 18-55 years undergoing post-bariatric abdominoplasty at
two public tertiary referral hospitals in Sao Paulo, Brazil. Eligible women had
been treated for previous obesity with bariatric surgery using the vertical
banded gastroplasty technique with Roux-en-Y gastric bypass by laparotomy; had
grade III contour deformity via the Pittsburgh rating scale; and had a post
bariatric body-mass index (BMI) lower than 32 kg/m2, with stabilised weight loss
for at least 6 months. Women were randomly assigned (1:1) to receive
postoperative iron supplementation with two intravenous infusions of 200 mg of
iron sucrose (intravenous group) or 100 mg of iron polymaltose complex orally
twice a day for 8 weeks (oral group). The primary outcome in both groups was
blood haemoglobin concentration at postoperative day 56 after abdominoplasty,
with a minimum clinically relevant difference of 1.5 g/dL. Analyses were
performed on an intention-to-treat basis. This trial is registered with
ClinicalTrials.gov, number NCT01857011, and the Brazilian Clinical Trials
Registry, number RBR-2JGRKQ. The trial is completed. FINDINGS: From April 7,
2014, to June 27, 2016, 102 post-bariatric patients were assessed for
eligibility. 56 patients were eligible and were randomly assigned, with 28
allocated to each group. Mean baseline haemoglobin concentration was slightly
higher in the oral group than in the intravenous group (12.71 g/dL [SD 1.06] vs
12.24 g/L [1.09]), and by post-operative day 56 was 12.54 g/dL (SD 1.18) and
12.80 g/dL (0.81), respectively (mean difference of 0.26 g/dL, 95% CI -0.28 to
0.80; p=0.009 in favour of the intravenous group). The minimum clinically
relevant difference in concentrations was not reached. No adverse events were
recorded in the intravenous group, whereas in the oral group, constipation was
recorded in five (18%) patients, diarrhoea in three (11%), and nausea in one (4%)
patient. INTERPRETATION: Postoperative intravenous administration of iron
increased haemoglobin concentrations at 56 days post-operatively and reduced iron
deficiency, without adverse events. Although superiority of intravenous iron was
not shown, intravenous administration might be useful in post-bariatric patients,
especially in those who have body-contouring treatment involving a second surgery
within a short period of time. Larger trials, and trials using higher intravenous
doses of iron, are needed to further assess the potential efficacy and safety of
intravenous iron administration after post-bariatric plastic surgery. FUNDING:
The Sao Paulo Research Foundation (FAPESP).
PMID- 29958572
TI - ?
PMID- 29958573
TI - ?
PMID- 29958574
TI - [Characteristics and epidemiology of chronic kidney disease].
AB - Today in France, more than 5% of the population suffers from chronic kidney
disease and its prevalence is increasing. It is important to detect these
pathologies early and to provide patients with a multidisciplinary care programme
in which nephrologists, endocrinologists and cardiologists coordinate their
approach.
PMID- 29958575
TI - [The care pathway of patients with chronic kidney failure].
AB - Chronic kidney failure is one of the pathologies identified by the French
national health authority as requiring a priority care pathway. The patient
undergoes a succession of life-changing events. The announcement of the need for
renal replacement therapy (kidney transplantation, peritoneal dialysis or
haemodialysis) marks the beginning of a life in which the patient must come to
terms with the disease and its treatment. Supporting the patient through all
these stages is essential and therapeutic education is crucial.
PMID- 29958576
TI - [Treatment of chronic kidney failure by haemodialysis].
AB - Haemodialysis is the most frequently used renal replacement therapy for chronic
kidney disease. Much progress has been made in this field since the invention of
this technique. The nurse nevertheless continues to play an essential role.
Kidney transplantation is gradually becoming the first-line treatment, the aim of
dialysis being to prepare patients for this procedure.
PMID- 29958577
TI - ["The acceptance of dialysis as a part of everyday life is a long road"].
AB - Dialysis is often seen as a burdensome constraint. The word induces fear, all the
more so as it evokes the image of a patient, attached to a machine some twelve
hours a week, undergoing a debilitating treatment in a highly medicalised
setting. However, it is possible to gradually accept this renal replacement
therapy by being supported and trained to use it independently. A patient
undergoing dialysis shares his story.
PMID- 29958578
TI - [Peritoneal dialysis, a first-line treatment?]
AB - The number of patients heading towards the terminal stage of their chronic kidney
disease, for the first time or after the failure of a kidney transplant, is
constantly growing, requiring the use of renal replacement therapy. Nowadays,
peritoneal dialysis can be given as a first-line treatment for most patients, in
the same way as haemodialysis. It allows patients to remain at home or in their
care facility, with the help of a private practice nurse when needed.
Complications can be quickly detected and resolved. In the event of failure, the
switch to haemodialysis is usually possible.
PMID- 29958579
TI - [Dietetics and nutritional management of kidney failure].
AB - Chronic kidney disease is associated with protein-energy malnutrition aggravated
by chronic inflammation, the presence of comorbidities and old age. Standardising
or reducing the intake of protein and salt are the first dietary objectives of
patients with kidney failure. Patients' sodium intake must be monitored at every
stage of the chronic disease. Regular nutritional follow-up is essential in order
to detect malnutrition. Therapeutic education favours the compliance of the
patient with the dietary recommendations.
PMID- 29958580
TI - [Kidney transplantation from Maastricht III donors after circulatory death,
overview of the situation in France].
AB - Organ retrieval from deceased donors after controlled circulatory arrest improves
access to kidney transplantation as a complement to brain dead donors. Authorised
since 2014, they represent a real opportunity for patients awaiting a kidney
transplant. The initial national results of the French protocol are encouraging.
PMID- 29958581
TI - [Transplantation, should patients have to be worthy of their donated organ?]
AB - Organ transplantation is a source of moral dilemmas resulting from the imbalance
between the demand and the availability of organs. In a context of shortage,
justice in the sense of 'equality' competes with justice in the sense of
'equity', which demands a rational distribution of rare resources. In human
affairs in general, when priorities need to be established, the most worthy are
generally favoured. Can worthiness feature among the selection criteria of
candidates awaiting a transplant?
PMID- 29958582
TI - [Serious somatic disease as a limit-experience: clinical aspect of end-stage
renal disease].
AB - Terminal kidney failure is a serious and irreversible somatic condition. The
ordeal of the disease can undermine the internal identity markers of patients,
prey to unbearable anxieties, exposing them to formlessness and a vacillating
identity.
PMID- 29958583
TI - [The detection of chronic kidney disease, a caregiver-user collaboration].
AB - For several years, the university hospital of Toulouse has been regularly
collaborating with the France Rein association to organise a kidney failure
screening day. A multidisciplinary team made up of student nurses, nurses,
dieticians, nephrologists and volunteers from the association, work with hospital
users to improve the prevention and treatment of people with kidney failure. This
approach is a real public health action.
PMID- 29958584
TI - [The future of kidney failure treatments].
AB - The future of nephrology lies in the miniaturisation of renal replacement
techniques, the development of the use of stem cells and xenotransplants.
Moreover, medicine must be personalised, from screening and throughout the care
pathway of the patient with chronic kidney failure. Thereby, the risk of
morbidity can be reduced and the quality of life improved, with the help of
connected tools. The role of the patients themselves and all healthcare
professionals is essential.
PMID- 29958585
TI - [Care, at the foundation of healthcare and social care].
AB - The ethics of 'care' invites us to found a concept of autonomy which is not
disconnected from that of vulnerability. Originally arising from a 'feminine'
gendered approach to morality, the notion of 'care' has become more extensive to
define a more complex model of justice, inclined to show that there is no
habitable world which does not involve the question of 'concern': in other words,
it is only habitable on the condition of having been previously, and
continuously, taken care of.
PMID- 29958586
TI - ?
PMID- 29958587
TI - ECG, July 2018.
PMID- 29958588
TI - Response to ECG, June 2018.
PMID- 29958589
TI - Congenital complete absence of tracheal rings with trifurcate carina: Case report
of a rare clinical and endoscopic presentation.
AB - We describe the case of a child with isolated absence of cartilaginous tracheal
rings and a trifurcate carina. At 6 months of age, the patient presented to our
multidisciplinary airway clinic with stridor and recurrent severe respiratory
infections requiring hospitalization. Radiographs showed airway narrowing. Exam
demonstrated biphasic stridor. Flexible fiberoptic laryngoscopy demonstrated only
mild laryngomalacia. Operative bronchoscopy demonstrated severe tracheomalacia
with absence of any visible tracheal rings and a trifurcate carina. Subsequent CT
imaging corroborated these findings and did not demonstrate any other major
abnormality. The patient did not require operative intervention and his
subsequent course was uncomplicated.
PMID- 29958590
TI - Clinical significance of spontaneous nystagmus in pediatric patients.
AB - OBJECTIVE: To analyze spontaneous nystagmus recorded in pediatric patients and
determine its diagnostic value. MATERIALS AND METHODS: Retrospective review of 86
patients (mean age = 13.9 +/- 4.7 years) with definitive spontaneous nystagmus
recorded by videonystagmography (VNG). Spontaneous nystagmus was categorized and
analyzed based on its characteristics. Correlations between spontaneous nystagmus
and established clinical diagnoses were explored. RESULTS: Among the patients
seen in a period of three years at our pediatric vestibular clinic, 15.4% (86 out
of 560) were found to have spontaneous nystagmus and half of them had horizontal
nystagmus with a fixed-direction. The majority of cases with spontaneous
nystagmus (77%, 66/86) were present without fixation only, while the presence of
spontaneous nystagmus with and without fixation was found in 16 patients (19%).
Most patients with spontaneous nystagmus without fixation only (68%) were
diagnosed with a peripheral vestibular disorder (e.g., vestibular neuritis) or
vestibular migraine. In contrast, vertical nystagmus was found in 15 patients,
most of whom had central vestibular disorders. Other rare forms of nystagmus or
abnormal eye movements, such as pendular nystagmus, ocular oscillation or flutter
were recorded in only four patients. CONCLUSIONS: Spontaneous nystagmus in
children and young adults with possible vestibular impairments may vary in
clinical presentation. Identification of its characteristics may help to make an
accurate clinical diagnosis. While spontaneous nystagmus associated with
peripheral vestibular disorders can be readily recognized, spontaneous nystagmus
in pediatric patients with vestibular migraine appears to be more complex and
variable in form.
PMID- 29958591
TI - A novel use of coblation in the treatment of subglottic stenosis.
AB - Bipolar radiofrequency plasma ablation (Coblation) technology has recently been
described in the treatment of airway stenosis. In these small case series and
case reports, the mucosal and submucosal tissues have been removed. We describe a
novel use of coblation technology, in which a coblation needle was used to
submucosally ablate subglottic stenosis in a 9 month-old girl with grade II
subglottic stenosis who had previously undergone multiple balloon dilations. This
technique spared the overlying mucosa, similar to that utilized in coblation
turbinoplasty. She experienced objective clinical improvement after the
intervention and has not required additional airway interventions to date.
PMID- 29958592
TI - Improving universal newborn hearing screening outcomes by conducting it with
thyroid screening.
AB - OBJECTIVES: One of the most important factors that can improve hearing screening
indicators is testing infants after 48 h of birth. The neonatal thyroid screening
program is done during the third to fifth day after birth in many countries. So
this screening is done at the appropriate time for hearing screening. The aim of
the present study was to evaluate hearing screening outcomes (the referral rate,
false positive rate, and positive predictive value) conducted with the thyroid
screening at the healthcare centers and compare the results with hospital before
discharge the infant. METHODS: This was a prospective exploratory cohort study.
The study population included all the newborns at a hospital (group 1) and
newborns who were referred to healthcare centers for thyroid screening (group 2),
except for infants with risk factors, from March 2012 to December 2017. Transient
evoked otoacoustic emissions (TEOAE) and automatic auditory brainstem response
(AABR) were used for the evaluation. The results were compared between the two
groups. RESULTS: Of the 4729 newborns, who participated in the study, 3001 were
referred from a hospital (group 1) and 1728 from two healthcare centers (group
2). The referral rate in group 1 and 2 was 16.1% and 7.6%, respectively. Also,
the false positive rate in group 1 and 2 was 15.9% and 7.6%, respectively. Our
study showed that the referral rate and false positive rate of hearing screening
in group 2 were significantly lower than that in group 1 (p < 0.001). The
positive predictive value in group 1 was significantly higher than that in group
2 (p < 0.05). There was no significant sex difference in any of the variables.
CONCLUSIONS: Our results showed that performing the hearing screening during the
thyroid program, instead of the hospital could be significantly improved
screening outcomes and suggest that hearing and thyroid screening together after
discharge from the hospital could be a good opportunity to introduce new
framework for hearing screening in many countries.
PMID- 29958593
TI - Airway evaluation in children with single ventricle cardiac physiology.
AB - OBJECTIVE: Children with single ventricle cardiac physiology (SVC) often require
airway procedures as an adjunct to their care. Descriptive analysis with a focus
on outcomes of airway procedures in SVC patients have not been fully described in
the literature. METHODS: Retrospective, single-center cohort review of 270
patients born between Aug-2007 and Jan-2017. Patients were identified by cardiac
database for single ventricle pathophysiology. A subset of these patients were
identified to have been evaluated by otolaryngology with airway evaluations
and/or interventions. RESULTS: 88/270 patients (32.6%) required investigation or
intervention for airway pathology. The most frequent procedure was flexible
fiberoptic laryngoscopy (58/88 patients); it was the only procedure performed in
40 patients. Seventeen patients required tracheostomies with an associated
increased length of stay (p < 0.001). Patients with cardiac procedures involving
dissection around the aortic arch were considered higher airway risk due to the
threat of recurrent laryngeal nerve injury, and were more likely to have vocal
cord paralysis (58%) compared to patients with lower risk procedures (21%; p <
0.001). However, on multivariate logistic regression, vocal cord paralysis did
not statistically impact the odds for tracheostomy placement, although the
presence of subglottic stenosis increased the odds ratio of tracheostomy by 14.7
(p = 0.02). CONCLUSIONS: Children with SVC often require airway evaluation and
intervention. Patients with high risk cardiac procedures had a higher risk of
recurrent laryngeal nerve injury but the presence of subglottic stenosis was the
best predictor for a tracheostomy. This study represents one of the largest
series of SVC children evaluated for airway pathology.
PMID- 29958594
TI - Auditory brainstem response in very preterm, moderately preterm and late preterm
infants.
AB - BACKGROUND: Auditory brainstem response across preterm infants help in
understanding difference if any in auditory maturation. OBJECTIVE: To analyze and
compare absolute and interpeak latencies of ABR in very preterm, moderate preterm
and late preterm infants at term age. METHOD: ABR traces were obtained from 148
ears of preterm infants (52 of very preterm, 44 of moderately preterm & 52 of
late preterm) at term age. ABR was recorded with 11.1/s clicks at different
intensity levels. RESULTS: Absolute latencies of peak I, III, V and interpeak
latencies of peak I-V, I-III and III-V were analyzed and compared between three
preterm groups. One way ANOVA was used to compare ABR parameters between three
groups of preterm infants and also to compare ABR parameters across various
gestation ages. There were no overall differences in absolute latencies,
interpeak latencies and amplitude of ABR between preterm groups and across
various gestation ages (P>0.05). Pearson correlation was used to find the
correlation between gestation age and ABR parameters. However, no correlation was
found. ABRs were similar among preterm groups at term age which reflects that the
brainstem maturation is similar among preterm groups. CONCLUSION: Gestational age
at birth does not seem to influence absolute and interpeak latencies of ABR at
term age. In preterm neonates, the findings lead to suggest that maturation of
auditory pathway occurs in a similar manner in preterm infants regardless of
gestational age at birth. We conclude that preterm birth alone as a risk factor
does not appear to have any marked effect on the development of ABR at term age.
PMID- 29958595
TI - Identification of key genes in cleft lip with or without cleft palate regulated
by miR-199a-5p.
AB - BACKGROUND: Cleft lip with or without cleft palate (CL/P) is one of the most
common congenital defects, which etiology involves both genetic and environmental
factors. Previous studies have shown that miR-199a-5p may mediate the occurrence
of CL/P. However, the key target genes regulated by miR-199a-5p are not clear. In
this study, we employed a systematic bioinformatics analysis of target genes
regulated by miR-199a-5p which may be involved in CL/P. METHODS: The miRBase,
Human miRNA tissue atlas, miRecords, miRpathDB, miRWalk, miRTarBase, DIANA
TarBase (v7.0), Literature search, DAVID software, Cytoscape plugin ClueGO +
Cluepedia app, MalaCards, TargetScanhuman7.1, Venny 2.1, STRING and GEO databases
were comprehensive employed to identify the key genes regulated by miR-199a-5p
associated with CL/P. RESULTS: Total 429 experimentally validated target genes
were obtained from five miRNAs related databases. Expressions of miR-199a-5p and
its experimentally validated target genes were elevated in bone, brain and skin.
KEGG pathway analysis revealed that the target genes were enriched in focal
adhesion, microRNAs in cancer and hippo signaling pathway. Biological process
categorization revealed that significant portions of the target genes were
grouped as transcription, DNA-templated. Total eight intersection genes were
identified by using MalaCards and TargetScanhuman7.1. The target gene
transforming growth factor alpha (TGFA) of miR-199a-5p involved in CL/P is
screened and verified. CONCLUSION: MiR-199a-5p may mediate CL/P by regulating key
target gene TGFA. The study may contribute to a better understanding of the
etiology of CL/P.
PMID- 29958596
TI - Failure rate in pediatric cochlear implantation and hearing results following
revision surgery.
AB - INTRODUCTION: In a discussion of the risks and benefits of pediatric cochlear
implantation, device failure and the need for revision surgery is often
overlooked. The failure rate has not been investigated extensively for this
population of patients. Hearing results are under-reported following revision
surgery as well. We will review our experience with cochlear implant failure,
revision, and hearing results when available to better guide the preoperative
counseling of families considering cochlear implantation. METHODS: Retrospective
chart review of all children undergoing cochlear implantation from 2004 to 2014.
RESULTS: In this review of 579 cases of pediatric cochlear implantation, a 4.7%
device failure rate was identified. Additionally, there was a 0.3% device
infection rate, as well as a 0.3% electrode extrusion rate. 10 patients had
audiometric data prior to and following revision surgery. These data demonstrate
similar pre-failure and post revision surgery pure tone average. CONCLUSION:
Cochlear implant device failure is the most common long-term complication of
surgery; fortunately, hearing outcomes following revision surgery, evaluated with
pure tone average, revealed no decline in auditory performance.
PMID- 29958597
TI - Understanding sociodemographic factors related to health outcomes in pediatric
obstructive sleep apnea.
AB - OBJECTIVES: (1) To examine relationships between socioeconomic status (SES) and
successful treatment of pediatric obstructive sleep apnea (OSA) with
adenotonsillectomy (T&A). (2) To explore sociodemographic factors and medical
comorbidities that separate OSA and refractory OSA populations in children.
METHODS: We retrospectively reviewed pediatric OSA patients (ages 0-18). Patients
evaluated for OSA by pediatric otolaryngology between January 2014 and December
2015 were included. OSA was defined as requiring T&A. Refractory OSA (ROSA) was
defined as recurring, polysomnography-proven, OSA after T&A, ultimately requiring
another intervention, such as a multi-level airway operation. Clinical data were
complemented with sociodemographic data. ZIP codes were used to approximate
median household income. RESULTS: Our cohort included 105 ROSA and 53 OSA
patients. These patients came from similar rates of single parent households and
coverage by public insurance. Median household income for OSA patients was
$47,086 (IQR $36,395-$60,196), compared to $45,696 (IQR $37,669-$56,203) for ROSA
patients. Over 60% of all patients fell below the national household income
average. Nearly half of the cohort resided in the three largest metro counties
closest to our institution. These patients represented higher rates of single
parent households (p = 0.045) and public insurance (p = 0.002), and trends
towards lower rates of ROSA (p = 0.138). CONCLUSION: Our results identified
sociodemographic factors that may influence healthcare compliance and
subsequently overall health outcomes. We identified no statistically significant
difference in measures of SES between patients with refractory vs non-refractory
OSA. Patients living closest to our medical center had lowest rates of ROSA,
suggesting that access to care may affect outcomes of pediatric OSA.
PMID- 29958598
TI - Pediatric recurrent acute mastoiditis: Risk factors and insights into
pathogenesis.
AB - OBJECTIVES: Recurrent acute mastoiditis is repeatedly reported in the literature,
but data to understand the pathogenesis, update treatment recommendations and
inform future trials are sparse due to the infrequency of the disease. METHODS: A
retrospective chart review from 2001 to 2016 was conducted including 73 children
treated for acute mastoiditis. A follow-up survey was attempted for each patient.
Bacteriology, method of treatment, hospital course, complications, and otologic
history were analyzed. A chi-squared test, Fisher's exact test and Mann-Whitney U
test compared recurrent acute mastoiditis to single acute mastoiditis cases.
Additionally, a comprehensive PubMed search and review of world literature
addressing recurrent pediatric acute mastoiditis was performed for comparative
purposes. RESULTS: Among 73 children with acute mastoiditis, six (8%) experienced
recurrent acute mastoiditis. Streptococcus pneumoniae was the only bacteria
isolated in this group. History of recurrent acute otitis media (>4 per year)
prior to the first episode of acute mastoiditis was identified in 24% with single
episode of acute mastoiditis and 83% with recurrent mastoiditis (p < 0.05). Fewer
intracranial/intratemporal complications were identified among recurrent
mastoiditis patients (p < 0.05). In a group of patients treated with more
extensive surgical communication during mastoidectomy for primary acute
mastoiditis (wide mastoidectomy with broad attic exposure and posterior
tympanotomy) no recurrence was observed. CONCLUSION: We identify multiple risk
factors associated with recurrence and provide early data supporting anatomic
predisposition to the development of recurrent acute mastoiditis. More aggressive
opening between the mastoid cavity and middle ear may prevent recurrent acute
mastoiditis episodes.
PMID- 29958599
TI - Transnasal adenoidectomy in mucopolysaccharidosis.
AB - BACKGROUND: Mucopolysaccharide (MPS) diseases are a heterogeneous group of
inherited, metabolic disorders characterized by accumulation of partially
degraded glycosaminoglycans (GAG) in multiple organ systems. Due to accumulation
in the airway, patients often present with multilevel airway obstruction and
obstructive sleep apnoea (OSA). Adenotonsillar surgery leads to a significant
improvement in the severity of OSA in MPS patients. However, access to secure the
airway and for conventional surgery can be challenging, due to limited neck
extension, macroglossia and reduced mouth opening. This study was undertaken to
evaluate the role of transnasal microdebridement and radiofrequent plasma
ablation (Coblation) in adenoidectomy to treat OSA in patients with MPS and
restricted airway access. METHODS: A retrospective case review was performed
including patients with MPS undergoing adenoidectomy for OSA in the period
between June 2015 and March 2017. In all cases, either a microdebrider (Gyrus
Diablo) or a Coblation wand (EVAC70, Smith&Nephew) was used via a transnasal
approach guided by nasendoscopy. The primary outcome was effect upon OSA,
measured by sleep oximetry and parental report of benefit. The secondary outcomes
were surgical complications and risk factors for persistent OSA after surgery.
RESULTS: A total of nine patients were identified with a mean age of 9 years
(range 3-14 years) at surgery. Post-operative sleep study data was available for
eight patients (8/9). Six patients (6/8) had improvement in 4% oxygen
desaturation index (ODI-4) with a mean of 8.11 pre-operatively (range 2.69-14.0)
and 4.99 postoperatively (range 0.68-8.48). ODI-4 did not improve in two (2/8)
patients. Irrespective of sleep oximetry results, improvement in OSA-related
symptoms was noted by all parents postoperatively. No risk factors for persistent
OSA were identified. Furthermore, no complications were noted in this cohort.
CONCLUSION: Transnasal Coblation and Microdebrider adenoidectomy is a safe and
effective surgical treatment for OSA in patients with Mucopolysaccharidosis and
adenoidal hypertrophy. As lifespan increases for patients with the
Mucopolysaccharidoses, greater emphasis is being given to optimising airway
management over the longer-term. This technical note describes the novel
application of endoscopic techniques for the management of primary adenoidal
hypertrophy when transoral access is restricted, or to debulk recurrent disease
that would be challenging to remove via the standard transoral route.
PMID- 29958600
TI - Wet and wounded: Pediatric facial trauma from swimming and diving.
AB - OBJECTIVES: Swimming has been reported as the most common recreational activity
among American youths, while diving remains a popular youth activity as well. We
characterize the most common facial injuries occurring during these activities
and evaluate facial fracture mechanisms and demographic trends, as this
information may be helpful in preventative counseling as well as diagnosis.
METHODS: The National Electronic Injury Surveillance System was assessed for
swimming- and diving-related facial injuries in children from 2007 to 2016.
Estimates of national injury incidence were recorded, and patient diagnoses,
demographics, and injury mechanisms were evaluated. RESULTS: In the 10-year
period assessed, 789 NEISS entries extrapolated to an estimated 27,709 patients
nationwide were analyzed. The yearly incidence fluctuated but steadily rose from
2013 to 2016. Males comprised a majority of injuries (58%), and laceration was
the most common diagnosis (65%), followed by abrasion/contusion (22%) and
fracture (9%). Facial fractures were most likely to involve the nasal bones
(87%). Swimming injuries were more numerous overall (74%), but a greater
proportion of diving injuries resulted in fracture (12% vs. 7%). Teenagers were
also more likely to suffer fractures than were younger children involved in the
same activities. CONCLUSION: Most analyses of swimming and diving injuries have
focused on spinal and orthopedic trauma. Nevertheless, the nature of headfirst
diving and swim strokes suggest facial trauma is an underappreciated concern for
clinicians. These findings reinforce the need for safer swimming and diving
practices and serve as a useful resource for physicians managing pediatric facial
injuries.
PMID- 29958601
TI - Adenotonsillectomy in children with sickle cell disease and obstructive sleep
apnea.
AB - INTRODUCTION: Obstructive sleep apnea (OSA) is prevalent and may be more severe
in children with Sickle Cell Disease (SCD) compared to the general pediatric
population. OBJECTIVES: The objective of this study was to describe the
therapeutic effects and complications of tonsillectomy and adenoidectomy (T&A)
for treatment of OSA in children with SCD. METHODS: A comprehensive database of
pediatric SCD patients was reviewed to identify all patients who underwent T&A
between 2010 and 2016. An IRB-approved, retrospective review of laboratory
values, perioperative course, pre- and post-T&A hospital utilization, and
polysomnography was conducted. RESULTS: There were 132 SCD children (108 HbSS)
who underwent T&A. Mean age was 7.6 +/- 4.6 years. The mean baseline hemoglobin
of these patients was 9.3 +/- 1.4 g/dL; 72.7% of patients had pre-operative
transfusion, such that the mean Hb at time of T&A was 11.4 +/- 1.0 g/dL. The
average admission length surrounding T&A was 3.5 +/- 1.2 days. Complications were
documented in 11.4% of operative cases. Polysomnography was available in 104 pre
T&A and 45 post-T&A. The Apnea-Hypopnea Index decreased on post-T&A polysomnogram
(7.6 +/- 8.7 vs. 1.3 +/- 1.9, p = 0.0001). The O2 nadir improved on post-T&A
polysomnogram (81.2 +/- 10.8 vs. 89.3 +/- 7, p = 0.0003). Emergency room visits
(mean events per year) decreased post-operatively (2.6 +/- 2.8 vs. 1.8 +/- 2.2, p
= 0.0002). CONCLUSIONS: T&A can be a safe and effective option to treat OSA in
pediatric patients with SCD and was significantly associated with reduced AHI and
fewer ER visits post-operatively.
PMID- 29958602
TI - Pediatric septoplasty and functional septorhinoplasty: A quality of life outcome
study.
AB - OBJECTIVE: This study assessed disease-specific quality-of-life outcomes among
pediatric patients undergoing septoplasty or functional septorhinoplasty. The
Nasal Obstruction Symptom Evaluation (NOSE) score was obtained pre- and post
operatively. Additional analyses determined whether demographics, nasal trauma,
prior nasal surgery, or allergic rhinitis history affected NOSE scores. METHODS:
Patients undergoing septoplasty or functional septorhinoplasty were evaluated
prospectively at a tertiary children's hospital. NOSE scores were assessed pre-
and post-operatively. Change in NOSE score was analyzed using the Wilcoxon Signed
Rank test, while multiple regression analysis evaluated factors associated with
NOSE score change. RESULTS: 136 patients (mean age 15.7 +/- 2.1 years) were
evaluated; 52 (38.2%) underwent septoplasty while 84 (61.8%) underwent functional
septorhinoplasty. Mean follow-up was 3.6 +/- 5.1 months. There was a
statistically significant decrease in NOSE score from pre-operative septoplasty
and functional septorhinoplasty: median = 75 to post-operative septoplasty:
median = 20 (z = -5.9, p < 0.001) and functional septorhinoplasty: median = 15 (z
= -7.9, p < 0.001). Gender, age, nasal trauma, prior nasal surgery, and allergic
rhinitis did not have a significant effect on NOSE score change for either group.
Additional surgery at the time of procedure was not a confounding variable in the
relationship between surgery type and NOSE score. A NOSE Scale reliability
analysis demonstrated high internal consistency with Cronbach's alpha of 0.83
across septoplasty and functional septorhinoplasty patients. CONCLUSION: There
was significant improvement in disease-specific quality-of-life in pediatric
patients undergoing septoplasty or functional septorhinoplasty. Gender, nasal
trauma, prior nasal surgery, and allergic rhinitis did not significantly affect
NOSE scores in either group.
PMID- 29958603
TI - The Sinus and Nasal Quality of Life Survey (SN-5) in the Management of Pediatric
Chronic Rhinosinusitis: A systematic review and meta-analysis.
AB - OBJECTIVES: Pediatric chronic rhinosinusitis (CRS) is a prevalent condition with
quality of life (QoL) impacts that are seldom reported in the literature. We
aimed to conduct a systematic review and meta-analysis on studies using the Sinus
and Nasal Quality of Life Survey (SN-5), the only validated symptom questionnaire
in pediatric CRS. METHODS: A literature search was conducted to identify studies
that used the SN-5 to measure QoL before and after medical or surgical
interventions for pediatric CRS. Comparison of means and standard deviations was
performed between pre- and post-intervention SN-5 scores. RESULTS: A total of 10
studies, consisting of 13 separate treatment arms of either medical therapy,
adenoidectomy, balloon catheter sinuplasty (BCS), or functional endoscopic sinus
surgery (FESS) were identified. The vast majority (92.3%) of the treatment arms
demonstrated minimal clinically important differences between baseline and post
intervention SN-5 scores. Rates of treatment success and minimal clinically
important difference among all treatment arms ranged from 43.2% to 94.0%.
Comparison of means showed an improvement in SN-5 score of 1.97 [95% CI, 1.18 to
2.76; p < 0.00001] for BCS, 1.83 [95% CI, 1.47 to 2.19; p < 0.00001] for FESS,
and 1.15 [95% CI, 0.36 to 2.66; p = 0.13) for medical treatment. CONCLUSION:
There is a paucity of literature on QoL outcomes in pediatric CRS. More studies
using the SN-5, particularly those controlling for baseline patient
characteristics, are necessary to fully elucidate the impact of various
interventions on QoL in pediatric CRS.
PMID- 29958605
TI - Incidence and associated risk factors for platinum-induced ototoxicity in
pediatric patients.
AB - OBJECTIVES: Platinum-based chemotherapy is effective against a variety of
pediatric malignancies. Unfortunately, the use of cisplatin and carboplatin can
lead to permanent and progressive sensorineural hearing loss which can affect the
quality of life of cancer survivors. The objectives of this study were to
evaluate the incidence of platinum-induced ototoxicity in children and analyze
potential risk factors. METHODS: Prospective cohort study. All pediatric patients
receiving chemotherapy with cisplatin and/or carboplatin from 01/2012 until
10/2017 were included. Hearing evaluations were performed before every
chemotherapy cycle, and following the end of chemotherapy, with auditory
brainstem response, otoacoustic emissions and/or audiometry. Demographics,
cumulative doses, cranial irradiation and exposure to other ototoxic agents were
analyzed. RESULTS: Twenty-eight patients were included, with a mean age of 7.2
years at the beginning of chemotherapy (range 5 months-15 years 2 months); twenty
one patients received cisplatin, four received carboplatin, and three received
both agents. Twelve patients had cranial irradiation and seven received another
ototoxic medication. The most frequent malignancies were germ cell tumors,
medulloblastoma and gliomas. Sensorineural hearing loss occurred in 28.6% of the
patients with a mean follow-up period of 21.5 months (range: 1-53 months). All
patients evaluated with audiometry had >= Chang 2b ototoxicity. Risk factors
include age less than 5 years, cranial irradiation, and cisplatin cumulative dose
greater than 400 mg/m2. CONCLUSION: Sensorineural hearing loss is a potential
side effect of platinum-based chemotherapy. Pediatric patients receiving
cisplatin chemotherapy with a cumulative dose exceeding 400 mg/m2, cranial
irradiation as well as patients younger than 5 years are at greater risk of
developing hearing loss.
PMID- 29958604
TI - Electrical dynamic range is only weakly associated with auditory performance and
speech recognition in long-term users of cochlear implants.
AB - OBJECTIVE: The electrical dynamic range (EDR) has been suggested to be related to
auditory performance in cochlear implant (CI) users. However, few reports have
evaluated postlingual CI users who have used CIs for long periods in comparison
with prelingual CI users. Here, we evaluated auditory perception and speech
performance in terms of the EDR in long-term CI users. The EDR, and auditory and
speech performances, were compared between pre- and post-lingual CI users.
METHODS: We enrolled all patients who received CIs from April 2000 to December
2010 at Seoul National University Hospital, and who had >=5 years of experience
with CIs. The EDRs affording subjective responses at the threshold level (T
level) and comfortable level (C-level) were analyzed in terms of their
relationships with pure tone audiometry levels, speech evaluation scores,
including those on the Phonetically Balanced (PB) Word List test, vowel and
consonant tests, a sentence test, and the Korean version of the Central Institute
for the Deaf (K-CID) test; we also calculated Category in Auditory Performance
(CAP) scores. RESULTS: We found no significant difference in the average EDR,
CAP, K-CID, PB word, consonant, or vowel scores between pre- and post-lingual CI
users. The EDR was weakly associated with the PB word (P = 0.003, r = 0.462) and
consonant scores (P = 0.005, r = 0.438). Other speech evaluations, such as the
CAP, K-CID, and vowel scores, were not significantly associated with the EDR T
level. We found no association between pure tone thresholds at 0.5, 1, or 2 kHz,
and the speech evaluation scores or EDRs of low-, middle-, or high-frequency
channels. CONCLUSIONS: The EDR was only weakly associated with speech
performance, such as scores on consonant and PB word tests in long-term CI users,
irrespective of pre- or post-lingual deafness status.
PMID- 29958606
TI - Congenital right bronchial stenosis with high bifurcation: Successful management
with side to side tracheobronchial anastomosis.
AB - Congenital bronchial stenosis is a rare entity [1,2]. While there are some
reports of congenital bronchial anomalies and their repair in the thoracic
literature this is first report in the literature of a bronchial take off just
below the larynx managed with surgical success. Here we present a case of a
former 33-weeker born with a tracheoesophageal fistula, Tetralogy of Fallot, and
a high bifurcation of the right mainstem bronchus with a concomitant long segment
bronchial stenosis. Preoperative planning included printing 3-D reconstructed
models of the airway to analyze various treatment options. At 3 months of age the
patient was taken to the operating room for surgical repair of the Tetralogy of
Fallot and side-to-side tracheobroncheoplasty. The patient was extubated on
postoperative day 3 and was discharged home without need for any ventilatory
support.
PMID- 29958607
TI - Turkish Adaptation of the Pediatric Voice Related Quality of Life Survey: A
validity and reliability study.
AB - OBJECTIVES: Childhood voice disorders have increased in recent years reduce not
only communication of the child, but also; the quality of life by affecting the
socio-emotional state. METHODS: In the study, it is aimed to test validity and
reliability of Pediatric Voice Related Quality of Life Survey (PVRQOL)'s Turkish
adaptation. A total of 223 individuals aged between 2 years and 18 years, with
and without voice problems were involved in this study. RESULTS: Statistically
significant differences were found between study and control groups for total
score and sub domain scores for PVRQOL (p < 0,001). Total score of quality of
life was higher in the control group. Cronbach alpha coefficient for overall
PVRQOL was 0,922; dimension of physical function was 0,894 and socio-emotional
domain was 0,804. In the test-retest reliability test, overall PVRQOL was found
to be 0,732; physical functional sub domain was 0,734; socio-emotional sub domain
was 0,721. The validity of the questionnaire was determined by factor analysis.
CONCLUSION: The results suggest that the Turkish version of the PVRQOL has
reliability and validity, and may play a crucial role in evaluating children with
voice disorders.
PMID- 29958608
TI - Including auditory tube function on models is relevant to assess water exposure
after tympanostomy tubes-Multiphase computerized fluid dynamics model.
AB - INTRODUCTION: Myringotomy with tympanostomy tube is the most common otologic
surgery and some patients are still advised to avoid water. However, there is no
evidence supporting this, with published papers questioning the need for this
advice. METHODS: A Multiphase Computational Fluid Dynamics (CFD) model was
created using computerized tomography images of a child's healthy ear. It was
then used to study the flow of fluids through the external ear, tympanic cavity,
and auditory tube, with and without submersion. RESULTS: The model accurately
described the behavior of the air retained in the patient's nasopharynx and
tympanic cavity. A simulated elevation of pressure in the external auditory canal
without submersion, without increase of pressure in the nasopharynx, demonstrated
that fluids promptly crossed the tympanostomy tube into the middle ear. However,
simulated elevation of pressure in the external auditory canal with concurrent
elevation of air pressure in the nasopharynx during submersion did not lead to
passive tube opening nor to any detectable flow through the tympanostomy tube.
CONCLUSIONS: In the model, submersion increases pressure in the nasopharynx which
offsets the pressure in the external auditory canal. So, in the absence of a
pressure gradient, no passive tubal opening took place, and no air or fluid flow
was detected through the transtympanic tube. This model now includes the exhaust
function of the auditory tube in the model and shows its relevance.
PMID- 29958609
TI - Prevalence of otitis media and risk-factors for sensorineural hearing loss among
infants attending Child Welfare Clinics in the Solomon Islands.
AB - OBJECTIVES: The present study aimed to assess the prevalence of otitis media and
risk-factors for sensorineural hearing loss among infants in the Solomon Islands,
in order to recommend an Infant Ear and Hearing Program that would be suitable to
the Pacific Island context. METHODS: Ear examinations and the JCIH Risk-Factor
Questionnaire were administered to 288 infants attending Child Welfare Clinics in
the Solomon Islands. RESULTS: Overall, 150 infants (52.084%) presented with
bilateral normal ear examinations and no risk-factors for SNHL. There were 73
infants (25.34%) with ear pathology in at least one ear, 13 (4.5%) of whom
required referral to the ENT Clinic for medical management. The most common
pathology was otitis media with effusion (OME) (21.87%). Infants aged 7-12 months
were significantly more likely to present with OME (p<0.001) and a history of
otitis media (p=0.017) than infants aged 0-6 months. There were 71 infants
(24.65%) with at least one risk-factor for sensorineural hearing loss. The most
common risk-factors were ototoxicity (8.3%), non-elective caesarean delivery
(6.59%), and possible in-utero syphilis infection (5.55%). CONCLUSIONS: The
prevalence of otitis media and risk-factors for sensorineural hearing loss
indicate the importance of initiating Infant Ear and Hearing Programs in the
Solomon Islands. Program should facilitate early education on prevention of ear
disease, as well as early diagnosis and management of children with hearing loss.
PMID- 29958610
TI - Utilization of diagnostic testing for pediatric sensorineural hearing loss.
AB - BACKGROUND/OBJECTIVE: Sensorineural hearing loss is a common diagnosis among
children. The diagnostic workup varies widely among practitioners. This study's
aim was to assess the utilization of diagnostic testing for SNHL and determine
the yield of each test. STUDY DESIGN: Retrospective chart review. SETTING:
Tertiary care center. SUBJECTS: 827 patients with a diagnosis of SNHL from
January 1, 2011 to January 1, 2015. RESULTS: 746 patients met inclusion criteria.
Temporal bone imaging was performed on 561 (75%) of patients with 224 (40%)
having positive results that explained the etiology of the SNHL. Congenital SNHL
was more likely to be associated with abnormal imaging than acquired SNHL
(109/299 versus 106/316 respectively) (p = 0.001). Unilateral SNHL was more
likely to be associated imaging abnormalities than bilateral SNHL (101/221 and
123/340 respectively) (p = 0.028). Genetic testing was performed on 244 (33%)
patients, of which 94 (39%) had abnormalities. Positive genetics results were
more common with bilateral than unilateral SNHL (82/191 and 12/53 respectively)
(p = 0.007). There was no statistically significant difference in the utility of
genetic testing for congenital and acquired SNHL (p = 0.0836). Cytomegalovirus
(CMV) testing was available for 104 (14%) of patients with 13 (12.5%) being
positive and consistent with congenital CMV. Electrocardiogram, urinalysis, and
Lyme titers were less useful. CONCLUSIONS: Imaging and genetic testing had the
highest yield in the evaluation of children with SNHL and were the most commonly
performed. CMV testing was valuable in neonates who failed newborn hearing
screening.
PMID- 29958611
TI - Vertigo in children; a narrative review of the various causes and their
management.
AB - Vertigo is a not an uncommon symptom in children, but often the treating doctors
are unsure of the diagnosis and the management of these cases. This narrative
review of the literature discusses the brief etiopathology, the clinical
manifestations and the management algorithm of most of the conditions causing
vertigo in children. The relevant information has been condensed into a table for
the perusal of the readers, which would assist in the appropriate management of
these children.
PMID- 29958612
TI - Otoacoustic emission suppression in children diagnosed with central auditory
processing disorder and speech in noise perception deficits.
AB - OBJECTIVE: The present study was designed to test the hypothesis that medial
olivocochlear system functionality is associated with speech recognition in
babble performance in children diagnosed with central auditory processing
disorder. METHOD: Children diagnosed with central auditory processing disorder
who specifically demonstrated speech in noise deficits were compared to children
diagnosed with central auditory processing disorder without these deficits.
Suppression effects were examined across 15 time intervals to examine
variability. Analysis of right and left ear suppression was performed separately
to evaluate laterality. STUDY SAMPLE: 52 children diagnosed with central auditory
processing disorder, aged 6-14 years were divided into normal or abnormal groups
based on SinB performance in each ear. Cut-off value was set at SNR = 1.33 dB.
Transient otoacoustic emissions suppression was measured. RESULTS: The abnormal
Speech in Babble Right Ear group showed significant negative correlations with
suppression levels for 7 of the 15 time intervals measured. No significant
correlations with SinBR performance were observed for the remaining time
intervals, as was the case for the typically evaluated R8-18 time interval and
the Speech in Babble Left Ear. CONCLUSIONS: Results indicate that suppression is
influenced by the time window analysed, and ear tested, and is associated with
speech recognition in babble performance in children with central auditory
processing disorder.
PMID- 29958613
TI - Internationally adopted children with cleft lip and/or cleft palate: Middle ear
findings and hearing during childhood.
AB - OBJECTIVE: Adopted children with cleft lip and/or cleft palate form a diverse
group of patients. Due to increased age at palatal repair, adopted children have
a higher risk of velopharyngeal insuffiency and poor speech outcome. Delayed
palate repair may also lead to longer lasting Eustachian tube dysfunction.
Decreased function of the Eustachian tube causes otitis media with effusion and
recurrent acute otitis media, which can lead to other middle ear problems and
hearing loss. METHODS: One-hundred-and-thirty-two adopted children treated by the
Cleft palate team in Wilhelmina Children's Hospital during January 1994 and
December 2014 were included. Retrospectively, middle ear findings, the need for
ventilation tube insertion and hearing during childhood were assessed. Findings
were compared with 132 locally born children with cleft lip and/or cleft palate.
RESULTS: Adopted children had a mean age of 26.5 months old when they arrived in
our country. After the age of two the total number of otitis media with effusion
episodes and the need for ventilation tube placement did not significantly differ
among adopted and non-adopted children. Adopted children had significantly more
tympanic membrane perforations. Hearing threshold levels normalized with
increasing age. Although within normal range, adopted children showed
significantly higher pure tone averages than locally born children when they were
eight to ten years old. CONCLUSION: In general, adopted patients with cleft lip
and/or cleft palate did not have more middle ear problems or ventilation tubes
during childhood. However, theyhave more tympanic membrane perforations.
PMID- 29958614
TI - Implementing a standardised discharge analgesia guideline to reduce paediatric
post tonsillectomy pain.
AB - OBJECTIVES: To reduce readmission for pain control post-paediatric tonsillectomy.
INTRODUCTION: Paediatric tonsillectomy is a common procedure in the UK.
Uncontrolled pain at home is a common reason for re-admission and therefore
adequate analgesic control following paediatric tonsillectomy is vital for a
smooth post-operative recovery. Analgesic regimens at a district general hospital
in England were audited and a standardised protocol was subsequently implemented.
METHODS: A retrospective audit from September 2014 to August 2015 was completed.
Discharge analgesic regimens and readmission rates post-tonsillectomy for
recurrent tonsillitis in 2-17 year-old children were studied in a large general
hospital in the United Kingdom. A standardised weight-based algorithm was used to
dose scheduled regular paracetamol for 2 weeks. Second cycle prospective audit
ran from December 2015 to November 2016. RESULTS: In cycle 1, 151 children (mean
age, 7.9 years) underwent tonsillectomy for tonsillitis, 25 (16.6%) of whom were
readmitted. 12 (7.9%) experienced postoperative haemorrhage, 13 (8.6%) required
pain control, and one (1.2%) had infection. The discharging analgesic regimen
varied widely and often included purchase of over-the-counter ibuprofen and
paracetamol. In cycle 2, 118 children (mean age, 8.8 years) underwent
tonsillectomy, 17 (14.4%) were readmitted; 12 (10.2%) had post-operative
haemorrhage, 0 needed pain control, 5 (4.2%) had other problems. There was a
significant reduction in readmission for pain control (p = 0.0027) from 7.3% to
0% in the study. There was no significant change in overall readmission rate
(16.6%-14.4%) or postoperative haemorrhage rate (8.9% overall). DISCUSSION:
Analgesia prescription post tonsillectomy varies widely and over the counter
prescriptions of ibuprofen and paracetamol is based on age rather than weight
with patients receiving inadequate analgesic doses. A readily available
standardised postoperative analgesic protocol can significantly reduce
readmission rates for pain control following paediatric tonsillectomy.
PMID- 29958615
TI - Infection of the spheno-occipital synchondrosis: A morbid complication following
adenoidectomy.
AB - Two 2-year-old males presented post-operatively following adenoidectomy with
persistent fever and neck stiffness. After multiple office visits, both patients
were admitted and found to have a widened spheno-occipital synchondrosis and
other imaging findings indicative of skull base osteomyelitis. Treatment with
antibiotics allowed for recovery with good long-term outcomes. Infection
involving the spheno-occiptal synchondrosis is rare and its circuitous
presentation of these two children no doubt led to delayed diagnosis.
PMID- 29958616
TI - Reducing the exposure of the tonsillar fossa does not impact postoperative pain
levels in children undergoing tonsillectomy: A double-blind randomized controlled
trial.
AB - BACKGROUND: It is not established whether reducing the exposure of the tonsillar
fossa would be an effective strategy for postoperative pain relief among the
pediatric population submitted to tonsillectomy. We assessed the impact of
closing this region using absorbable sutures on pain, on the resumption of normal
diet and on the healing process until seven days after surgery. METHODS:
Randomized, double-blind, controlled trial comparing postoperative pain in 132
children between the ages of 5 and 12 years undergoing tonsillectomy having
bilateral closure, unilateral closure or non-closure of the tonsillar fossa.
RESULTS: No differences in pain levels were reported both at discharge and on
postoperative day 7. The day of resumption of normal diet was similar in all
patients. Less granuloma and edema of the uvula were noted in patients with non
closure of the tonsillar fossa. CONCLUSION: These results showed that reducing
the exposure of the tonsillar fossa after the removal of the palatine tonsils was
not an effective method for postoperative pain relief in children. Moreover, its
closure was associated with slower healing.
PMID- 29958617
TI - Supraglottoplasty surgery types 1-3: A practical classification system for
laryngomalacia surgery.
AB - OBJECTIVE: The objective of this study is to review the published literature on
supraglottoplasty techniques for correcting laryngomalacia, and to subsequently
provide a standardized classification system. METHODS: Three authors
independently and systematically searched Pubmed/MEDLINE and six additional
databases for all studies that included descriptions of supraglottoplasty
techniques for correcting laryngomalacia. Sub-sites operated on and specific
technique descriptions were reviewed, cataloged and subsequently categorized.
This data was then used to develop a new classification system. RESULTS: 231
articles were identified, downloaded and reviewed in full text. 53 articles with
1669 patients from the included articles described in detail the
supraglottoplasty procedure. 84 articles with 5731 patients had to be excluded
secondary to not providing detail about the supraglottoplasty procedure. The
resultant data identifies the need for a more standardized reporting of the
supraglottoplasty procedure in order to more accurately evaluate technique
specific outcomes. Currently 77% of the patients in the literature cannot be
assessed for outcomes as they did not describe the details for the procedures.
Eight variations of supraglottoplasty and four variations of epiglottis surgery
were described. Based on the literature, we consolidated the surgery into the
following types: Type 1: Debulking of arytenoids, Type 2: Division of
aryepiglottic folds, Type 3: Epiglottis surgery. CONCLUSION: This descriptive
review identified 53 articles with 1669 patients from the included articles
detailing multiple variations of supraglottoplasty techniques. The new
classification supplements a previously established system describing
laryngomalacia, and simplifies the supraglottoplasty into three descriptive and
logical types of categories. Our classification system would give surgeons a
universal language to describe the supraglottoplasty performed, which could
improve reporting of techniques, and facilitate future communication and
research.
PMID- 29958618
TI - Screening for hearing loss among school going children.
AB - Hearing loss results from a deviation in the perception of sounds in one's
environment. A child may have hearing loss at a hearing threshold of >=16 dB.
Hearing loss is among the frequent disorders and affects lots of people globally.
Hearing loss negatively affects many areas needed for classroom learning,
language development, academic performance, and social development. These
consequences can be reduced by early detection with appropriate audiological and
speech therapy interventions. In developing countries like Ghana, there is no
such laid down formal hearing screening programs for early detection of any signs
of impairments. The present study was aimed at identifying the prevalence and
causes of hearing loss among basic school children aged between 5 and 17 years at
Freetown Basic School, Ho. The study sought to determine the causes and
prevalence of hearing loss. Out of the 210 participants, 44 (21%) failed the
audiometric screening test. Out of the 44 students who failed the audiometric
screening test, 25 (11.9%) had hearing loss across all the test frequencies.
Prevalence of hearing loss among basic school children was found to be 11.9%.
This shows that hearing loss is not uncommon among school going children in the
Ho Municipality. It was determined from the study that the prevailing causes of
the hearing impairments may be attributable to abused use of ototoxic drugs and
ear-aches and infections with majority of participants recording mild hearing
loss. It can be concluded that hearing loss among school going children is
preventable if appropriate measures are put in place.
PMID- 29958620
TI - The use of honey in cochlear implant associated wounds in pediatric patients.
AB - INTRODUCTION: The use of honey in wound care is becoming more common due to the
proven benefit in all three phases of wound healing, as well as the antibacterial
and antibiofilm properties. We present our experience using TheraHoney gel, a
medical grade honey, for the successful treatment of cochlear implant associated
skin breakdown. OBJECTIVE: To describe the role of TheraHoney gel in the
management of cutaneous infection and ulceration associated with cochlear
implants. METHODS: Three cases of wounds treated traditionally with antibiotics,
plus the addition of TheraHoney, were retrospectively reviewed. The first patient
had a superficial 1 * 1 cm ulcer, the second patient had bilateral ulcers: one
superficial 1.5 * 1.5 cm ulcer and the other a 1.5 * 2 cm stage III pressure
ulcer with an exposed receiver stimulator, and the third patient with a 3 * 3.5
cm stage III ulcer with an exposed receiver stimulator. RESULTS: With the
addition of TheraHoney gel, complete wound closure was achieved at all three
patients without the need for surgical reconstruction. CONCLUSION: Cutaneous
infection with or without skin breakdown is a common delayed complication after
cochlear implantation. We demonstrate the efficacy of adding medical grade honey
in promoting healing in infected scalp pressure ulcers overlying the cochlear
implant site.
PMID- 29958619
TI - Evaluating the impact of translated written discharge instructions for patients
with limited English language proficiency.
AB - INTRODUCTION: Patients with limited English language proficiency have indicated
that they believe post-operative instructions written in their native language
will improve comprehension over verbal translation alone, but the effect of this
has not been previously studied. We hypothesize that providing written discharge
instructions in Spanish for native Spanish speakers will improve comprehension
regarding post-operative care after routine otolaryngologic procedures when
compared to instructions written in English. METHODS: This prospective randomized
controlled trial enrolled subjects who met criteria from June 2016 to November
2016. Subjects were Spanish-speaking parents and legal guardians of children
undergoing tympanostomy tube insertion, adenoidectomy, and/or tonsillectomy.
Subjects were given written discharge instructions in either English or Spanish.
Both cohorts received standard verbal counseling in Spanish as well. Primary
outcome was score on a standardized quiz assessing comprehension of discharge
instructions. Patient satisfaction and preferences were secondary outcomes
assessed through a survey. Participants underwent follow up one month after
initial enrollment. RESULTS: Twenty subjects were enrolled, with ten receiving
written discharge instructions in Spanish and ten receiving instructions written
in English. There was no significant difference in comprehension scores between
the two groups. Eleven participants completed the survey on patient satisfaction
and preferences. Most subjects (91%, 10/11, p<0.01) preferred written
instructions in their native language and subjectively felt this would improve
their comprehension. However, there was no significant effect on patient
satisfaction. CONCLUSIONS: Spanish-speaking patients indicate a strong preference
for written discharge instructions in their native language, although there was
no significant difference in short-term comprehension of instructions written in
English vs. Spanish on objective evaluation. Accommodating these preferences may
improve long-term comprehension and patient satisfaction, and ultimately build
invaluable rapport between providers and patients.
PMID- 29958621
TI - Increased anti- EBV VCA IgG antibody levels are associated with need for surgery
in patients developing upper respiratory tract complications.
AB - INTRODUCTION: The immune reaction developing against Ebstein-Barr virus (EBV)
infection may be one of the major determinants of severe adenoid hypertrophy (AH)
and chronic otitis media with effusion (COME) needing surgery. In this study, we
aimed to investigate the relationship between these antibodies and the need for
surgery due to complications such as severe AH and COME. METHODS: Sixty
consecutive patients <15 years old who were admitted to our outpatient clinics
between January 2014 and December 2015 with severe AH +/- COME and underwent
adenoidectomy +/- ventilation tube insertion and 129 control patients who had a
history of EBV infection at least three months before the inclusion to the study
without current symptoms of upper airway obstruction and middle ear disease were
included in this study. Two groups of patients and a control group were studied:
a) children who underwent adenoidectomy alone with no middle ear disease (group
1), b) children with COME and AH who underwent adenoidectomy and tympanostomy
with ventilation tube insertion (group 2), and c) control group without adenoid
hypertrophy or otitis media with effusion. RESULTS: Patients who needed surgery
(Group 1 and 2) had significantly higher levels of anti-EBV VCA IgG antibodies
than control patients (19.8 +/- 16.4 vs. 1.7 +/- 0.8 S/CO, p < 0.001). Anti-EBV
VCA IgM levels did not differ between groups. Group 2 patients had also higher
levels of Anti-EBV VCA IgG antibodies than group 1 patients (35.8 +/- 16.7 vs.
11.8 +/- 8.5 S/CO, p < 0.001). ROC curve analysis resulted in a cut-off point of
2.92 S/CO level for anti-EBV VCA IgG antibodies for need for surgery in EBV
infected patients with 97% sensitivity and 98% specificity. CONCLUSION: Markedly
increased serum anti-EBV VCA IgG antibodies in children who developed upper
respiratory tract complications such as severe AH and COME may show the
significant role of enhanced immune system reaction in the pathogenesis of these
complications due to EBV infection.
PMID- 29958622
TI - Clinical outcomes following CochlearTM BIA300 bone anchored hearing aid
implantation in children.
AB - OBJECTIVE: Bone anchored hearing implants (BAHI) have been in use for over 30
years, and are commonly implanted in children for a range of indications. The
CochlearTM BIA300 system was launched in 2010 and used at The Birmingham
Children's Hospital from 2011. Here we report the long-term outcomes of children
implanted with the CochlearTM BIA300 BAHI system in our centre. METHODS: A
retrospective case note analysis was performed to identify outcomes in all
children who underwent BIA300 implantation between 2011 and 2013. RESULTS: 52
children with a total of 78 implants were included. Mean age at implantation was
8.7 years. Mean follow-up was 43.5 months. Overall, 60 (77%) implants developed
soft tissue complications requiring treatment. Forty-eight (62%) required topical
treatment; 27 (35%) required systemic treatment; and 27 (35%) required surgical
soft tissue revision under general anaesthesia. CONCLUSIONS: The CochlearTM
BIA300 system appears to be associated with higher than expected rates of soft
tissue reaction in children, with late as well as early soft tissue complications
requiring both medical and surgical treatment.
PMID- 29958623
TI - Posterior cricoid-graft mismatch in laryngotracheal reconstruction.
AB - INTRODUCTION/OBJECTIVE: In laryngotracheal reconstruction (LTR) with sutureless
posterior cricoid grafting (PCG), the inset graft's thickness may not precisely
approximate the anterior-posterior depth of the divided posterior cricoid plate.
This case series highlights this phenomenon and describes the clinical profiles
and airway characteristics of children with similar subglottic stenosis grades
undergoing LTR with PCG with varying degrees of graft-cricoid mismatch. METHODS:
This is a case series with retrospective chart review of children who underwent
LTR with PCG by a single surgeon at a tertiary care urban children's hospital
from 2008 to 2014. RESULTS: Twenty-one patients with twenty-two operations were
identified. Varying degrees of graft-cricoid mismatch were present. Of the 22
operations, 15 were classified as grade I (flush), 5 grade II (<3 mm), and 2
grade III (>3 mm). Median preoperative grade of stenosis was III in all groups.
Mean one month granulation grade was 1.84, compared to 1.92 in grade I, 1.6 in
grade II mismatch, 2 in grade III mismatch, and 1.7 in any mismatch (p = 0.65).
Mean follow up was 24 months. CONCLUSION: Graft-cricoid mismatch may occur at
variable degrees during laryngotracheal reconstruction utilizing sutureless
posterior cricoid grafting. Our preliminary data suggest several millimeters of
graft-cricoid mismatch can be tolerated without significantly affecting
postoperative granulation formation or adding to postoperative morbidity.
PMID- 29958624
TI - Functional septorhinoplasty in the pediatric and adolescent patient.
AB - OBJECTIVES: To describe pediatric and adolescent patients undergoing functional
septorhinoplasty and to analyze both subjective and objective outcomes. METHODS:
Retrospective review of prospective cohort study of patients <=18 years old
undergoing functional septorhinoplasty between 2013 and 2016 at a tertiary care
center. Patient demographics, nasal exam, procedure, and pre- and postoperative
nasal obstruction symptom evaluation (NOSE) score, EuroQOL 5-dimension (EQ5D),
and peak nasal inspiratory flow (PNIF) scores were analyzed. RESULTS: 39
patients, 48.7% male, mean age 15.9 years (range 7-18), with nasal obstruction
underwent functional septorhinoplasty with mean follow up of 8.5 months. Patients
reported a history of allergies (46.5%), nasal fracture (59.0%), and previous
nasal surgery (25.6%). Most common exam findings included internal nasal valve
narrowing (92.3%), superior/dorsal septal deviation (74.4%), external nasal valve
narrowing (43.6%), caudal septal deviation (35.9%), and a narrow middle vault
(33.3%). Septal cartilage grafts were placed in 79.5% of patients and PDS plate
was used in 28.2%. Most common procedures included spreader grafts (84.6%),
columellar strut graft (30.8%), and swinging door (23.1%). Of patients with both
baseline and postoperative scores, at last follow up NOSE scores (SD) decreased
from 59.0 (23.7) to 21.2 (8.8) (n = 26, p < 0.001), EQ5D VAS scores increased
from 76.2 (17.7) to 85.8 (13.5), (n = 19, p = 0.056), and PNIF scores increased
from 66.2 (25.3) to 90.8 (46) L/min, (n = 13, p < 0.01); all mean differences met
the minimal clinically important difference for each score. 2 patients underwent
revision surgery and there was one complication of a nasal abscess. CONCLUSIONS:
Functional septorhinoplasty is safe and effective in select pediatric and
adolescent patients with significant nasal obstruction and results in significant
improvements in both subjective and objective outcomes measures.
PMID- 29958625
TI - Manipulating macrophage polarization and function using classical HDAC
inhibitors: Implications for autoimmunity and inflammation.
AB - Macrophages are important player in defense against invading pathogens and their
dysfunction is linked to most of inflammatory and autoimmune diseases.
Inflammation is a normal and physiological response of the immune system against
harmful stimuli such as infection and injury. However, when allowed to continue
unchecked, under certain conditions it turns into autoimmune or inflammatory
diseases, neurodegeneration, and carcinogenesis. Currently, several safe and
effective anti-inflammatory drugs are available with many more drugs in the
development pipeline, among which are histone deacetylase inhibitors. In this
review we discuss how post-translational modifications of histones influence the
innate and adaptive immunity through macrophage survival, proliferation,
polarization and functional responses. We also discuss how emerging classes of
pharmacological agents which developed for use as anti-cancer agents, have been
applied as anti-inflammatory drugs to treat macrophage-mediated inflammatory and
autoimmune diseases.
PMID- 29958626
TI - Incidence and clinical parameters associated with eribulin mesylate-induced
peripheral neuropathy.
AB - Eribulin mesylate is a microtubule-targeting agent that has been approved for the
treatment of breast cancer and liposarcoma. Due to its novel mechanism of action,
eribulin therapy induces a distinct profile of adverse events, including
peripheral neuropathy. However, the incidence and risk of eribulin-related
neurotoxicities are unclear. Here, we conducted a systematic search of PubMed and
Embase from their inception to October 2017. Eligible studies included trials in
which eribulin was intravenously administered at a standard dose of 1.4 mg/m2
over 2-5 minutes on days 1 and 8 on a 21-day cycle. The events of all-grade and
high-grade peripheral neuropathy were collected to calculate the overall
incidence and relative risk (RR). A total of thirty-two studies containing 6129
subjects were included in this analysis. The incidences of all-grade and high
grade eribulin monotherapy-related peripheral neuropathy were 28% (95% confidence
interval [CI], 24%-32%) and 4% (95% CI, 3%-5%), respectively. Subgroup analysis
further revealed that a higher incidence of neurotoxicities was observed in
patients with breast cancer and those with longer treatment duration. Moreover,
eribulin-treated subjects had a significantly increased risk of all-grade (RR,
2.00; 95% CI, 1.70-2.35; p = 0.008) and high-grade (RR, 3.68; 95% CI, 2.30-5.89;
p<0.001) neurotoxicities. Our results suggested that patients treated with
eribulin had an increased risk of developing peripheral neuropathy.
PMID- 29958627
TI - Antiangiogenic therapy: Markers of response, "normalization" and resistance.
AB - Currently in cancer treatment, one premise is to use antiangiogenic therapies in
association with chemotherapy or radiotherapy to augment their efficacy by
benefiting from the vascular "normalization" induced by antiangiogenic therapy.
This concept defines the time during which the tumor blood vessels adopt normal
like morphology and functionality, i.e. the blood vessels become more mature, the
perfusion augments and hypoxia decreases. To date, there is such a diversity of
treatment protocols where the type of antiangiogenic to adopt, its dose and
duration of administration are different, that knowing when and how to treat is
problematic. In this review, we analyzed thoroughly preclinical and clinical
studies that use antiangiogenic treatments to benefit from the "normalization"
and showed that the effects depend on the type of antiangiogenic administrated
(anti-VEGF, anti-VEGFR, Multi-Kinase Inhibitor) and on the duration of treatment.
Finally, biomarkers of "normalization" and resistance that could be used in the
clinic are presented.
PMID- 29958628
TI - Therapeutic perspectives for brain metastases in non-oncogene addicted non-small
cell lung cancer (NSCLC): Towards a less dismal future?
AB - Risk of brain metastases (BM) affects a remarkable number of non-small cell lung
cancer (NSCLC) patients, impacting on their quality of life (QoL) and prognosis.
While tyrosine-kinase inhibitors (TKIs) showed interesting intracranial control
rates in oncogene-addicted NSCLC, BM still represent an unmet need for the
counterpart without driver gene mutations. For these patients, new treatment
options include anti-angiogenic drugs and immune-checkpoint inhibitors, possibly
combined with standard chemotherapy, even though the benefit on BM has not been
clearly defined. A multidisciplinary team including neurosurgeons, medical and
radiation oncologists is needed in order to integrate systemic and loco-regional
strategies at the right time point. Ad-hoc designed clinical trials are slowly
emerging for previously treated patients with uncontrolled BM. The aim of this
review is to offer a detailed and updated picture of possible approaches for non
oncogene-addicted NSCLC patients having BM, in order to support clinicians in
their daily practice.
PMID- 29958629
TI - Therapeutic vaccines and immune checkpoints inhibition options for gynecological
cancers.
AB - Treatments for gynecological cancer include surgery, chemotherapy, and radiation.
However, overall survival is not improved, and novel approaches are needed.
Immunotherapy has been proven efficacious in various types of cancers and
multiple approaches have been recently developed. Since numerous gynecological
cancers are associated to human papilloma virus (HPV) infections, therapeutic
vaccines, targeting HPV epitopes, have been developed. The advancing
understanding of the immune system, regulatory pathways and tumor
microenvironment have produced a major interest in immune checkpoint blockade,
Indeed, immune checkpoint molecules are important clinical targets in a wide
variety of tumors, including gynecological. In this review, we will describe the
immunotherapeutic targets and modalities available and review the most recent
immunotherapeutic clinical trials in the context of gynecological cancers. The
synergic results obtained from the combination of HPV therapeutic vaccines with
radiotherapy, chemotherapy, or immune checkpoint inhibitors, may underlie the
potential for a novel therapeutic scenario for these tumors.
PMID- 29958630
TI - Glutathione system in animal model of solid tumors: From regulation to
therapeutic target.
AB - Glutathione (GSH) is one of the most important defenses against oxidative stress
through the fine-tuned regulation of redox homeostasis. Glutathione is also
involved in many metabolic processes and is important for the regulation of cell
survival, proliferation, and death. Furthermore, GSH and the enzymes that are
involved in its biosynthesis, catabolism, and detoxification (e.g., disulfide
oxidized glutathione, glutathione S-transferase, glutathione peroxidase,
glutathione reductase, and gamma-glutamyltranspetidase) play an important role in
several diseases, including cancer. In cancer cells, these enzymes protect the
tumor microenvironment against oxidative stress and cell death and are important
for tumor growth and development. Thus, the GSH system is an important tool for
investigating new pharmacological approaches for cancer treatment. Several
preclinical models of solid tumors are available for this purpose. This review
summarizes and discusses the regulation and dysregulation of GSH and its related
enzymes in different models of solid tumors, and potential treatments that target
the GSH system.
PMID- 29958632
TI - A revisited concept. Tumors: Wounds that do not heal.
AB - In 1986, Harold F. Dvorak, Professor of Pathology at Harvard Medical School
Boston, published an essay in the New England Journal of Medicine entitled
"Tumors: Wounds that do not heal" pointed out that similarities exist between
tumor stroma generation and wound healing. Cancers share many features in common
with tissue regeneration, including immune response, cell proliferation, cell
migration, tissue remodeling, and cell death. In this review article, we analyze
the importance and the limits of this concept, which confirm the close
relationship between two apparently different biological processes.
PMID- 29958631
TI - Perioperative chemotherapy for urothelial carcinoma of the upper urinary tract: A
systematic review and meta-analysis.
AB - INTRODUCTION: Upper tract urothelial carcinomas are rare malignancies with
differences in anatomy and biology requiring therapeutic strategies that differ
from bladder cancer. The role of perioperative systemic therapy in this disease
remains uncertain with limited data to support its use. A systematic review of
the literature and meta-analysis was therefore undertaken to provide more
information and guide clinical practice. METHODS: A literature search was
performed using Embase and Medline databases with additional searches performed
manually using terms associated with upper tract urothelial malignancies. Data
was extracted from studies of patients that underwent nephrouretectomy for the
management of upper tract urothelial carcinoma and received either neoadjuvant or
adjuvant systemic therapy. Overall survival (OS), disease-free survival (DFS),
and cancer-specific survival (CSS) were summated and analyzed using Cochrane
Revman software Version 5.3. RESULTS: There were 13 comparative studies and no
randomized studies identified for data extraction; 11 adjuvant and 2 neoadjuvant
with 1170 patients receiving perioperative systemic therapy and 3472 controls
that did not. Perioperative chemotherapy was associated with improved OS (HR
0.75, 95%CI 0.57-0.99), DFS (HR 0.54, 95%CI 0.32-0.92), and CSS (HR 0.69, 95%CI
0.42-1.15). CONCLUSIONS: The available data suggests that perioperative systemic
therapy is associated with improved survival in patients with upper tract
urothelial cancer.
PMID- 29958633
TI - Molecular targets of celastrol in cancer: Recent trends and advancements.
AB - Despite the advancement in the well-equipped and sophisticated laboratories and
facilities, cancer remains to be a major cause of death worldwide. Consequently,
further investigation of novel strategies need to be evolved. Since the last few
decades, the utilization of phytochemicals is emerging against several human
cancers, including lung, breast, colon carcinoma, lymphoma, and other
hematological malignancies. Terpenoids are a category of therapeutically active
phytochemicals that have been utilized against cancer, cardiovascular and
neurodegenerative disorders. Particularly, celastrol, a pentacyclic terpenoid, is
well-studied for its variety of pharmacological properties. It is well documented
that celastrol can modulate a variety of signaling pathways. Celastrol's anti
proliferative role has been found to be associated with its pro-apoptotic (via
protein kinase B), anti-angiogenic (via vascular endothelial growth factor and
vascular endothelial growth factor receptor), anti-metastatic (via matrix
metalloproteinases), and anti-inflammatory (via cytokines and chemokines)
activities. This review describes various molecular mechanisms of celastrol for
understanding the biology of cancer initiation, progression as well as designing
efficacious therapeutic strategies.
PMID- 29958634
TI - Radiation therapy in renal cell carcinoma.
AB - Renal cell carcinoma (RCC) is classically regarded as extremely resistant to
classical fractionated radiation therapy (RT). Nowadays, there is convincing data
supporting RCC radiosensitivity to high fraction doses, which may represent an
ideal issue for new treatment strategies in primary and oligometastatic RCC
disease. This review discusses the role of RT in RCC and its potential
therapeutic scenario focusing on the most interesting clinical trials.
PMID- 29958635
TI - Tafro syndrome: Critical review for clinicians and pathologists.
AB - TAFRO is an acrostic and includes thrombocytopenia (T), anasarca (A), fever (F),
reticulin fibrosis (R) and organomegaly (O) (Takai et al., 2013). TAFRO syndrome
has been described firstly by Takai in Japanese patients. However TAFRO cases
have been reported from US, Europe and other countries (Takai et al., 2010; Iwaki
et al., 2016; Abdo et al., 2014). Three major and at least one minor criteria and
exclusion of infectious, rheumatologic and neoplastic diseases are required for
the diagnosis of TAFRO. In fact TAFRO must be thought in clinically undiagnosed
and unsolved problemmatic cases.
PMID- 29958637
TI - Don't Hang Up Your Lead, Yet.
PMID- 29958636
TI - Targeting the cellular schizophrenia. Likely employment of the antipsychotic
agent pimozide in treatment of refractory cancers and glioblastoma.
AB - Pimozide is currently being used in clinic as a neuroleptic and exerts versatile
biological actions. Pimozide is a cationic amphiphilic drug (CAD); CADs block the
synthesis of neutral lipids, impair cholesterol homeostasis of cancer cells and
increase accumulation of diacylglycerol-3-phosphate. Pimozide exerts tumoricidal
activity which was first shown for melanoma and neuroblastoma via proposed anti-
dopaminergic effects. Recently, pancreas cancers are shown to elevate dopamine
receptor-2 synthesis, which is blocked by pimozide leading growth inhibition.
Besides binding to inner mitochondrial membrane and reducing cellular
respiration, pimozide also inhibits calmodulin, T-type calcium channels and sigma
receptors which all correlate with tumor-inhibitory functions. Pimozide also
exerts chemotherapy and radiotherapy-sensitizing effects in cancer cells and acts
as an inhibitor of STAT-3 and STAT-5 signaling proteins with potential activity
in leukemia, liver and prostate cancer. Pimozide also blocks stem cell features
and Wnt-beta/catenin signaling in liver cancer. Pimozide interferes with Fatty
Acid Protein Binding-4 and activates PPAR-gamma and it was proposed to alleviate
cancer cachexia. Besides mechanisms of calmodulin and sigma-receptor associated
pathways, pimozide was proposed to inhibit glioblastoma via serotonin receptor 5
HT7. Pimozide is a selective inducer of autophagy and also inhibits ubiquitine
specific protease (USP-1) which may associate with its chemosensizing potential
in lung cancer and glioblastoma. Via versatile mechanisms of tumoricidal actions
and due to its highly traversing capability through the blood-brain barrier,
pimozide highly deserves to be studied in animal models of drug resistant
refractory cancers and glioblastoma, which have very poor prognosis.
PMID- 29958638
TI - Editorial.
PMID- 29958639
TI - Featuring: Has the robot caught up? National trends in utilization, perioperative
outcomes, and cost for open, laparoscopic, and robotic pediatric pyeloplasty in
the United States from 2003 to 2015.
PMID- 29958640
TI - Commentary to: 'Non-stented versus stented urethroplasty for distal hypospadias
repair: A systematic review and meta-analysis'.
PMID- 29958641
TI - Description of mutation spectrum and polymorphism of Wilms' tumor 1 (WT1) gene in
hypospadias patients in the Indonesian population.
AB - INTRODUCTION: Hypospadias is one of the most common congenital anomalies of the
penis. Previous studies reported mutation of the Wilms' tumor 1 (WT1) gene as a
cause of hypospadias. The aim of this study is to describe the WT1 mutation
spectrum and polymorphism in hypospadias patients in Indonesia. MATERIAL AND
METHODS: DNA was isolated from 74 hypospadias patients at the Division of
Pediatric Surgery, Department of Surgery Hasan Sadikin Hospital. All exons in the
WT1 gene were amplified by a PCR method, followed by Sanger sequencing. Mutation
analysis was performed using BioEdit software and in silico analysis using
Mutation Taster, Polymorphism Phenotyping-2 (PolyPhen-2), and Sorting Intolerant
from Tolerant (SIFT). RESULT: DNA analysis results showed two types of
heterozygous mutations in five subjects (Table), hence the frequency of WT1
mutations was 6.7% (10/148 allele). The first mutation was a missense mutation
identified in twin boys. The second was a novel heterozygous alteration in the
non-coding region nine bp upstream of exon 6 (c.366-9T>C), which was identified
in three patients. One heterozygous polymorphism in the coding region of exon 7
(c.471A>G/rs16754) was identified in 10 subjects. This variant did not cause any
change in amino acid products (silence polymorphism). Allele frequency for the G
allele (mutant allele) and A allele (wild type) was 13.5% and 86.5%,
respectively. DISCUSSION: WT1 is one of the best known hypospadias genes. The WT1
gene is involved in male genital development in the early and late periods of sex
determination, and hence is known as a long-term expression gene in genitalia
development. Mutation analysis of WT1 in a Chinese population identified that the
WT1 mutation frequency was 4.4%. The WT1 mutation frequency identified in the
present study was higher, at 6.7%. Coincidentally, research subjects with p.R158H
variants were monozygotic twin siblings with midshaft hypospadias accompanied by
undescended testis in one and penoscrotal hypospadia with micropenis in the
other. The incidence of familial hypospadias in male siblings suffering from
hypospadias was reported to be 9.6% in a study conducted by Sorensen et al.
Moreover, in the present study polymorphism c.471A>G(rs16754) at exon 7 was
identified heterozygously in 10 research subjects (minor allele frequency 13.5%).
CONCLUSION: WT1 mutations were identified in only a few cases of hypospadias and
most of these were syndromic. This result implies that mutation of WT1 is not a
common cause of hypospadias in the Indonesian population.
PMID- 29958642
TI - Adolescent urology.
PMID- 29958643
TI - The implications of fellowship expansion on future pediatric urologist surgical
volumes.
AB - INTRODUCTION: Over the past 25 years, Pediatric Urology fellowship programs
accredited by the Accreditation Council for Graduate Medical Education (ACGME)
have more than doubled. This increase may lead to a significant decrease in the
number of operative cases per surgeon and therefore impact the current practice
of pediatric urology. OBJECTIVE: The objective in conducting this study is to try
and predict the effect of the current number of pediatric urology fellowship
training positions on future case volume per surgeon using a mathematical model
and to discuss future management of the pediatric urology workforce. DESIGN: The
current study employed a mathematical model to predict the effect of the number
of fellowship graduates on future "case volume per surgeon". We incorporated
population growth rates, to calculate incidence rates of key
procedures/conditions and the anticipated retirement rate of the current pool of
pediatric urologists to help calculate this. RESULTS: There is a possibility to
increase the number of practicing board-certified pediatric urologists in the
next 30 years from approximately 325 to 900 (figure). There will be a twofold
reduction in case volume per surgeon compared to the present in model 1. In model
2 the decrease in case volumes is less significant. The annual number of fellows
needed to obtain a future-to-current ratio equal to 1 is 16 for model 1, and 26
for model 2. DISCUSSION: Our study demonstrates, by using two different models
that the current number of pediatric urology fellowship training positions in the
United States will ultimately lead to a significant decrease in the case volume
per surgeons. Our model has limitations as it relies on multiple assumptions. We
are assuming that all fellowship positions would be filled every year and that
all fellows would graduate, establish their practices in the United States, and
devote 100% of their assumed 30-year professional career to pediatric urology. We
also made assumptions of disease occurrence and need for surgical correction. The
final assumption we made was that the birth rate would stay static over the next
30 years even though it has been declining for many decades. CONCLUSION: This
exercise, even with its inherent limitations, is still sufficient to demonstrate
that fellowship expansion warrants thoughtful discussion.
PMID- 29958644
TI - Commentary to "The implications of fellowship expansion on future pediatric
urologist surgical volumes".
PMID- 29958646
TI - CEVL interactive: Regional nerve blocks in everyday pediatric urology: 1.
Ultrasound guided regional anesthetic block of ilioinguinal and iliohypogastric
nerves (USGIINB).
PMID- 29958645
TI - Laparoscopic inguinal hernia repair by modified peritoneal leaflet closure:
Description and initial results in children.
AB - INTRODUCTION: Inguinal hernias are common in infants and children. While the gold
standard for hernia repair in the pediatric period has been via an open inguinal
incision with dissection and high ligation of the hernia sac, over the past two
decades laparoscopic herniorrhaphy has increased in popularity. The advantages of
laparoscopy include decreased post-operative pain, improved cosmetic results,
ability to easily assess the contralateral side for an open internal inguinal
ring, and decreased risk of metachronous hernias. Herein, we describe a modified
laparoscopic herniorrhaphy using a peritoneal leaflet closure and report our
operative experience with intermediate-term results. METHODS: We retrospectively
reviewed our IRB-approved registry for all children who underwent initial
laparoscopic herniorrhaphy at our tertiary care center over a 2.5-year period.
All surgeries were performed by a single surgeon using a technique we have termed
the peritoneal leaflet closure. This technique involves incising the peritoneum
circumferentially around the open internal ring and developing peritoneal
leaflets which are then closed together over the ring with a running non
absorbable barbed stitch (Figure). Intraoperative findings and complications,
operative times, and post-operative complications were reviewed for all children.
RESULTS: A total of 50 initial laparoscopic hernia repairs (4 bilateral, 42
unilateral) were performed in 46 children (43 boys, 3 girls) at a median age of
5.9 years (range 0.5-16.7). Median operative time was 73 min (range 48-138) for
unilateral and 106 min (range 104-135) for bilateral herniorrhaphy. No patient
had an intraoperative complication. Two children (4%) had contralateral open
rings discovered at time of surgery and underwent unplanned bilateral
laparoscopic hernia repair. All patients went home on the same day as the
procedure and three children (6%) had minor post-operative complaints (umbilical
bulge, thigh pain, and urine holding) that all self-resolved. Thirty-nine
children had follow-up data available. Intermediate-term complications occurred
in two children (5%): one boy developed a contralateral hydrocele (despite a
closed ring at surgery) and one boy had a hernia recurrence that required open
repair. Overall, operative success with the modified peritoneal leaflet closure
technique was therefore 97% (38 of 39 children with follow-up). All 37 boys who
followed up had bilateral descended testes of normal size and consistency.
CONCLUSIONS: Laparoscopic herniorrhaphy using a peritoneal leaflet closure
technique is safe and effective when used in infants and children to close an
indirect hernia (i.e. patent processus vaginalis). No intraoperative
complications occurred in this cohort and success rate was 97%.
PMID- 29958647
TI - Expert opinion: Regional nerve blocks in everyday pediatric urology: 1.
Ultrasound guided regional anesthetic block of ilioinguinal and iliohypogastric
nerves (USGIINB).
PMID- 29958648
TI - People who report practicing interdental cleaning frequently are less likely to
have caries and periodontal disease.
PMID- 29958649
TI - 6-millimeter implants seem to have lower survival than 10-mm implants with or
without bone augmentation after 5 years when single posterior missing teeth are
replaced.
PMID- 29958650
TI - A novel approach for benchmarking and assessing the performance of state
estimators.
AB - State estimation is a widely adopted soft sensing technique that incorporates
predictions from an accurate model of the process and measurements to provide
reliable estimates of unmeasured variables. The reliability of such estimators is
threatened by measurement related challenges and model inaccuracies. In this
article, a method for benchmarking of state estimation techniques is proposed.
This method can be used to quantify the performance and hence reliability of an
estimator. The Hurst exponents of a posteriori filtering errors are analyzed to
characterize a benchmark (minimum mean squared error) estimator, similar to the
minimum variance control benchmark developed for control loops. A distance metric
is then used to quantify the extent of deviation of an estimator from the
benchmark. The proposed technique is developed for linear systems and extended to
non-linear systems with single as well as multiple measurable variables.
Simulation studies are carried out with Kalman based as well as Monte Carlo based
estimators whose computational details are significantly different. Results
reveal that the technique serves as a tool that can quantify the performance and
assess the reliability of a state estimator. The strengths and limitations of the
proposed technique are discussed with guidelines on applications and deployment
of the technique in a real life system.
PMID- 29958651
TI - Decentralized coordinated control of elastic web winding systems without tension
sensor.
AB - In elastic web winding systems, precise regulation of web tension in each span is
critical to ensure final product quality, and to achieve low cost by reducing the
occurrence of web break or fold. Generally, web winding systems use load cells or
swing rolls as tension sensors, which add cost, reduce system reliability and
increase the difficulty of control. In this paper, a decentralized coordinated
control scheme with tension observers is designed for a three-motor web-winding
system. First, two tension observers are proposed to estimate the unwinding and
winding tension. The designed observers consider the essential dynamic, radius,
and inertial variation effects and only require the modest computational effort.
Then, using the estimated tensions as feedback signals, a robust decentralized
coordinated controller is adopted to reduce the interaction between subsystems.
Asymptotic stabilities of the observer error dynamics and the closed-loop winding
systems are demonstrated via Lyapunov stability theory. The observer gains and
the controller gains can be obtained by solving matrix inequalities. Finally,
some simulations and experiments are performed on a paper winding setup to test
the performance of the designed observers and the observer-base DCC method,
respectively.
PMID- 29958652
TI - The influence of obesity and weight gain on quality of life according to the SF
36 for individuals of the dynamic follow-up cohort of the University of Navarra.
AB - BACKGROUND: The health-related quality of life is an important element for the
comprehensive assessment of overweight and obesity. OBJECTIVE: To assess the
impact of obesity and weight gain on the health-related quality of life of the
dynamic cohort of the Follow-up Program of the University of Navarra. MATERIAL
AND METHODS: The analysis included 10,033 participants of the prospective dynamic
cohort of the Follow-up Project of the University of Navarra, with a response
rate of approximately 90%. The quality of life was measured with the Short Form
36 Health Survey (SF-36) (0, worst quality of life; 100, best quality of life).
The statistical analysis was performed with generalized lineal models (mean of
each SF-36 domain and 95% CI). A difference of 3 points was considered clinically
relevant. RESULTS: The SF-36 analysis showed that physical function, general
health and the physical component summary were inferior in individuals with
excess weight and obesity at the start of the study, compared with individuals
with normal weight. The study population with unchanged excess weight or obesity
after 2 years of follow-up presented lower scores on the SF-36 domains
corresponding to physical function, body pain, physical component summary and
general health than individuals who maintained the normal weight category
according to BMI (kg/m2). CONCLUSIONS: Obesity appears to be associated with a
negative impact on health-related quality of life, affecting the physical area
more significantly than the psychosocial.
PMID- 29958653
TI - 2-hydroxycaproate predicts cardiovascular mortality in patients with
atherosclerotic disease.
AB - BACKGROUND AND AIMS: We aimed to identify novel biomarkers for cardiovascular
mortality through a non-targeted metabolomics approach in patients with
established atherosclerotic disease from the Tor Vergata Atherosclerosis Registry
(TVAR). METHODS: We compared the serum baseline metabolome of 19 patients with
atherosclerosis suffering from cardiovascular death during follow-up with the
baseline serum metabolome of 20 control patients matched for age, gender, body
mass index (BMI) and atherosclerotic disease status, who survived during the
observation period. RESULTS: Three metabolites were significantly different in
the cardiovascular mortality (CVM) group compared to controls: 2-hydroxycaproate,
gluconate and sorbitol. 2-hydroxycaproate (otherwise known as alpha hydroxy
caproate) was also significantly correlated with time to death. The metabolites
performed better when combined together rather than singularly on the
identification of CVM status. CONCLUSIONS: Our analysis led to identify few
metabolites potentially amenable of translation into the clinical practice as
biomarkers for specific metabolic changes in the cardiovascular system in
patients with established atherosclerotic disease.
PMID- 29958655
TI - Association between attention-deficit/hyperactivity disorder and amyotrophic
lateral sclerosis.
PMID- 29958654
TI - [Comparative costs study between ready-to-administer bag of gemcitabine and
production in reconstitution unit].
AB - INTRODUCTION: Dose-banding is needed to rationalise cytotoxic drugs preparations.
A new step was recently crossed: gemcitabine is the first molecule to be sold in
ready-to-administer bag. What's the pharmaco-economic impact of gemcitabine ready
to-administer bags versus manufacturing in preparation unit? METHODS: A
retrospective analysis of gemcitabine dosage prepared over three months permitted
to explain our consumption of this drug, and by modelling, to characterize the
good prescription interval for each dosage. Compared costs study assessed cost of
medicine, preparation kit and preparation time. RESULTS: Over the study period,
for 5%, 7.5% and 10% of deviation, respectively 67%, 75% and 76% of preparations
were covered by standard doses. We chose 7.5% interval. The manufacturing cost of
gemcitabine infusions is around 30,000?/year for vials with solution for
infusion, 32,300? for vials with powder, versus 67,300? for ready-to-administer
bag. Approximately 7.75minutes of pharmacy technician time would be saved by
preparation. DISCUSSION: Ready-to-administer bags of gemcitabine allow relevant
coverage of manufacturing doses. The annual extra cost would reach 37,200? for
our establishment. But, it can be justified by expected benefits: safer
medication circuit, saving time of pharmacy technician....
PMID- 29958656
TI - Meta-analysis of histopathological outcomes of laparoscopic assisted rectal
resection (LARR) vs open rectal resection (ORR) for carcinoma.
AB - BACKGROUND: We conducted a meta-analysis of the randomized evidence to determine
the relative merits of histopathological outcomes of laparoscopic assisted (LARR)
versus open rectal resection (ORR) for rectal cancer. DATA SOURCES: A search of
PubMed and other electronic databases comparing LARR and ORR between Jan 2000 and
June 2016 was performed. Histopathological variables analyzed included; location
of rectal tumors; complete and incomplete TME; positive and negative
circumferential resection margins (+/-CRM); positive distal resected margins
(+DRM); distance of tumor from DRM; number of lymph nodes harvested; resected
specimen length; tumor size and perforated rectum. RESULTS: Fourteen RCTs
totaling 3843 patients (LARR = 2096, ORR = 1747) were analyzed. Comparable
effects were noted for all these histopathological variables except for the
variable perforated rectum which favored ORR. CONCLUSIONS: LARR compares
favorably to ORR for rectal cancer treatment. However, there is significantly
higher risk of rectal perforation during LARR compared to ORR.
PMID- 29958657
TI - Managing barriers to recycling in the operating room.
AB - BACKGROUND: Among hospital staff, little is known concerning barriers to
recycling and perception of waste in the operating room (OR), despite continued
improvement in recycling programs. This study sought to identify barriers to OR
recycling and implement a recycling improvement educational program. METHODS: A
survey was administered within Mayo Clinic at four campuses. Based on survey
results, a recycling improvement program was devised and implemented at a surgery
center in Paradise Valley, Arizona. A cost-savings analysis was performed
thereafter. RESULTS: Of 524 participants, 56.7% reported being unclear which OR
items are recyclable, and 47.7% thought the greatest barrier to recycling was
lack of knowledge. After implementation of the recycling educational program,
cost savings of 10.3% (p = 0.004) were achieved in sharps waste disposal when
compared to the previous year at the surgery center. CONCLUSIONS: Addressing
barriers to recycling in the OR can significantly reduce waste and save valuable
healthcare dollars.
PMID- 29958659
TI - Stent-graft treatment of an ascending aortic false aneurysm after surgical aortic
valve replacement.
PMID- 29958660
TI - Proximal aortic surgery in the elderly: Is age just a number?
PMID- 29958658
TI - Recent Developments in Single-Cell RNA-Seq of Microorganisms.
AB - Single-cell transcriptome analysis through next-generation sequencing (single
cell RNA-seq) has been used broadly to address important biological questions. It
has proved to be very powerful, and many exciting new biological discoveries have
been achieved in the last decade. Its application has greatly improved our
understanding of diverse biological processes and the underlying molecular
mechanisms, an understanding that would not have been achievable by conventional
analysis based on bulk populations. However, so far, single-cell RNA-seq analysis
has been used mostly for higher organisms. For microorganisms, single-cell RNA
seq has not been widely used, mainly because the stiff cell wall prevents
effective lysis, much less starting RNA material is obtained, and the RNA lacks
polyadenylated tails for universal priming of mRNA molecules. In general, the
detection efficiency of current single-cell RNA-seq technologies is very low, and
further development or improvement of these technologies is required for
exploring the microbial world at single-cell resolution. Here, we briefly review
recent developments in single-cell RNA-seq of microorganisms and discuss current
challenges and future directions.
PMID- 29958661
TI - All roads lead to Rome... really?
PMID- 29958662
TI - Uh-oh, some CO2 has gone missing.
PMID- 29958663
TI - Aortic symmetry index: Initial validation of a novel preoperative predictor of
recurrent aortic insufficiency after valve-sparing aortic root reconstruction.
PMID- 29958664
TI - Left ventricular assist device therapy in a patient with hearing and speech
disabilities.
PMID- 29958665
TI - Is allograft aortic valve replacement still an option? When, which, where?
PMID- 29958666
TI - Hitting "turbo" after the race is done: Subpulmonic support in failed Fontan
circulation.
PMID- 29958667
TI - The best is yet to come: Repair of thoracoabdominal aortic aneurysms.
PMID- 29958668
TI - Mitral valve repair versus replacement for infective endocarditis. What is better
in the "real world"?
PMID- 29958669
TI - Surgical management of moderate ischemic mitral regurgitation at the time of
coronary artery bypass grafting remains controversial.
PMID- 29958670
TI - Patient reminder and recall interventions to improve immunization rates: A
Cochrane review summary.
PMID- 29958671
TI - Selective Serotonin Reuptake Inhibitors Reduce Longitudinal Growth in Risperidone
Treated Boys.
AB - OBJECTIVES: To examine whether selective serotonin reuptake inhibitors (SSRIs)
inhibit longitudinal growth in children and adolescents, particularly in the
early stages of puberty, using a sample of convenience comprising risperidone
treated boys. STUDY DESIGN: Data from four clinic-based studies in risperidone
treated 5- to 17-year-old boys with no general medical conditions were combined
for this analysis. Anthropometric measurements and psychotropic treatment history
were extracted from the medical and pharmacy records. Linear mixed effects
regression analyses examined the association between SSRI use and change in age
sex-specific height and body mass index z scores, after adjusting for relevant
confounders. RESULTS: Risperidone-treated boys (n = 267; age: 12.7 +/- 2.7
years), 71% of whom had ever taken an SSRI, contributed to the analysis. After
adjusting for age, psychostimulant and antipsychotic use, and time in the study,
both the duration of SSRI use as well as the cumulative dose were inversely
associated with height z score after age 11 years (P < .0001). After adjusting
for baseline height, duration of SSRI use was most strongly inversely associated
with height z score in Tanner stages 3 and 4 boys who took SSRIs continuously (r
= -0.69, P < .009). No association was observed with body mass index z score.
CONCLUSIONS: In risperidone-treated boys, SSRI use is associated with reduced
longitudinal growth, particularly in those undergoing puberty. Whether adult
height or other metabolic or psychological outcomes are affected remains to be
determined.
PMID- 29958672
TI - Peer Relationship Outcomes of School-Age Children Born Very Preterm.
AB - OBJECTIVES: To characterize the friendship networks, peer relationships, and
bullying experiences of 12-year-old children born extremely preterm (EPT; 23-27
weeks of gestation), very preterm (VPT; 28-32 weeks of gestation), and full term
(FT; 38-41 weeks of gestation), and to identify child characteristics placing
children at risk of peer problems. STUDY DESIGN: A regional cohort of 44 EPT, 60
VPT, and 109 FT born children were followed prospectively to 12 years of age. The
nature of children's close friendships, peer relations, and bullying experiences
were assessed using a multimethod approach, including parent, teacher, and child
report. RESULTS: Across all measures, children born EPT had more peer social
difficulties than children born VPT and FT. They were more likely to report no
close friendships (5%-14% EPT vs 0%-3% VPT/FT), dissatisfaction with their peer
network (16% vs 1%-2%), and less time interacting face-to-face with friends (16%
23% vs 5%-8%). They were also 3 times more likely to be rated by their parents
and teachers as experiencing problems relating to peers (P <= .001). In contrast,
rates of chronic bullying (>=2 times/week) were similar for EPT and VPT children
(12%-14% vs 4% FT). Emotional problems, inattention/hyperactivity, and motor
deficits were associated with an increased risk of peer relationship problems,
whereas higher body mass index, delayed pubertal development, vision problems,
and inattention/hyperactivity problems were associated with frequent bullying.
CONCLUSIONS: With the exception of bullying, risks of peer social difficulties
were greatest among children born EPT. Peer social relationships should be
monitored as part of longer term developmental surveillance and support.
PMID- 29958673
TI - Resilience Rather than Medical Factors: How Parents Predict Quality of Life of
Their Sick Newborn.
AB - OBJECTIVE: To assess the influence of resiliency and stress on parental
perspectives of the future quality of life (QOL) of neonatal intensive care unit
(NICU) newborns at high risk of neurodevelopmental disability. STUDY DESIGN: We
conducted a prospective multicenter questionnaire study. Perspectives from
parents of newborns at high risk of disability as per neonatal follow-up criteria
were compared with a low-risk group consisting of parents of all other NICU
newborns. Parental anxiety and resiliency, measured using Brief Symptom Inventory
and Sense of Coherence scales, respectively, were associated with QOL
projections. RESULTS: Parents returned 129 (81%) questionnaires. Parents
considering their newborn as currently sicker were more stressed (P = .011) and
worried about future physical (P < .001) and mental (P < .001) health, QOL (P <
.001), coping (P = .019), and financial (P < .001) and emotional (P = .002)
impact on the family. Ooverall, there was no difference between parents of high
risk and low-risk newborns on QOL projections. Almost all parents projected a
good future QOL. Less resilient parents projected more pain (P = .04), more
financial (P = .019), and emotional (P = .031) impact on their family, and were
10 times more likely to predict that their newborn would remain chronically ill.
CONCLUSIONS: Parental projection of future QOL of NICU newborns is not associated
with risk of disability. Most parents predict overall a good future QOL and focus
more on familial impact. The Sense of Coherence scale may be used in clinical
settings to identify less resilient parents.
PMID- 29958674
TI - Blood Glucose and Cerebral Tissue Oxygenation Immediately after Birth-An
Observational Study.
AB - OBJECTIVE: To assess a possible association of blood glucose concentration with
cerebral regional oxygen saturation (crSO2) and cerebral fractional tissue oxygen
extraction (cFTOE) in neonates born at term and preterm 15 minutes after birth.
STUDY DESIGN: A post-hoc analysis of secondary outcome measures of 2 prospective
observational studies was performed. Neonates born at term and preterm via
cesarean delivery were included if cerebral near-infrared spectroscopy
measurements were performed during the immediate transition after birth and blood
glucose concentrations were measured at 15-20 minutes after birth. Arterial
oxygen saturation and heart rate were measured with pulse oximetry. cFTOE was
calculated from arterial oxygen saturation and crSO2 values. crSO2 and cFTOE 15
minutes after birth were correlated with blood glucose concentrations. RESULTS:
Seventy-five infants were included. In 50 neonates born at term, crSO2 and cFTOE
15 minutes after birth were 83 +/- 7.7% and 0.14 +/- 0.08, respectively. In 25
neonates born preterm, crSO2 and cFTOE 15 minutes after birth were 80.2 +/-
12.1%, and 0.15 +/- 0.1, respectively. crSO2 and cFTOE correlated significantly
with blood glucose concentrations in neonates born at term and preterm.
Increasing blood glucose concentrations were associated with decreasing crSO2 in
neonates born at term (q = -0.35, P = .01) and neonates born preterm (q = -0.69,
P = .01) and with increasing cFTOE in neonates born at term (q = 0.31, P = .03)
and neonates born preterm (q = 0.67, P = .01). CONCLUSIONS: Blood glucose
concentration was associated with cerebral oxygenation during the immediate
transition after birth in neonates born at term and preterm.
PMID- 29958675
TI - Ambulatory Visits for Otitis Media before and after the Introduction of
Pneumococcal Conjugate Vaccination.
AB - OBJECTIVE: To examine the long-term trend of otitis media (OM)-associated
ambulatory visits from 1997 to 2014 and to evaluate the impact of 7-valent and 13
valent pneumococcal conjugate vaccines (PCV7 and PCV13) on OM ambulatory visits.
STUDY DESIGN: We examined OM-associated ambulatory visits in children, using the
National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical
Care Survey. RESULTS: A total of 24 148 OM-related visits were identified from
363 240 ambulatory visits. OM visits accounted for 9.5% of all ambulatory visits
in 1997-1999, 7.1% in 2002-2009, and 5.5% in 2012-2014. Between the pre-PCV7 and
the post-PCV13 period, annual physician's office visits for OM declined from 826
to 387 visits per 1000 children among children younger than 2 years of age.
Compared with the pre-PCV7 period, office visit rates for OM significantly
declined by 51% (95% CI 42%-58%) among children younger than 2 years of age and
by 37% (95% CI 23%-48%) among children 2-4 years of age during the post-PCV13
period. Among children younger than 2 years of age, emergency department visits
for OM declined by 47% (95% CI 36%-55%) during the post-PCV13 period, and
hospital outpatient visits declined by 30% (95% CI 8%-48%) during the PCV13
transition period. OM-related visits declined across sex, race/ethnicity, health
insurance status, and geographic region. CONCLUSION: Our nationwide study shows
that ambulatory visits for OM have declined following the introduction of PCV7
and PCV13. Future research on the evolving microbiology of OM and continued
monitoring of the epidemiology of pneumococcal disease are needed.
PMID- 29958676
TI - Is substance P a nasal epithelial neuropeptide?
PMID- 29958677
TI - Synthetic Clay-based Hypoxia Mimetic Hydrogel for Pulp Regeneration: The Impact
on Cell Activity and Release Kinetics Based on Dental Pulp-derived Cells In
Vitro.
AB - INTRODUCTION: Thixotropic synthetic clays have been successfully used for tissue
engineering in regenerative medicine. The impact of these clays on the dental
pulp, in particular in combination with hypoxia-based approaches using hypoxia
mimetic agents (HMAs), is unknown. Our aim was to reveal the response of dental
pulp-derived cells (DPCs) to a synthetic clay-based hydrogel and evaluate the
release of HMAs. METHODS: Using resazurin-based toxicity assays, live-dead
staining, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
staining, the viability of human DPCs seeded onto a synthetic clay-based hydrogel
of 5%-0.15% as well as onto the hydrogels loaded with the HMAs
dimethyloxalylglycine (DMOG), desferrioxamine, L-mimosine, and CoCl2 was
evaluated. Furthermore, supernatant of the hydrogels loaded with HMAs were
generated. Vascular endothelial growth factor (VEGF) production of DPCs in
response to the supernatant was measured to reveal the cellular response to the
HMAs. RESULTS: We found that the synthetic clay-based hydrogel did not impair the
viability of DPCs. Cell monolayer and cell cluster formations were observed on
the hydrogel. No significant increase of VEGF levels was observed in the
supernatant when DPCs were cultured on hydrogels loaded with HMAs. Supernatant of
DMOG-loaded hydrogels stimulated VEGF production in DPCs in the first hour,
whereas the effect of desferrioxamine, L-mimosine, and CoCl2 did not reach a
level of significance. CONCLUSIONS: The synthetic clay-based hydrogel represents
a promising biomaterial that does not induce prominent toxic effects in DPCs. It
can be loaded with DMOG to induce hypoxia mimetic activity. Overall, we provided
first insights into the impact of synthetic clays on DPCs for tissue engineering
purposes in regenerative endodontics.
PMID- 29958678
TI - Continuing conversations: Debates about adverse childhood experiences (ACEs)
screening.
PMID- 29958679
TI - HOPE-ful bottles: Examining the potential for Hawaii's opportunity probation with
enforcement (HOPE) to help mainstream therapeutic jurisprudence.
AB - This article builds on the emerging understanding of Hawaii's Opportunity
Probation with Enforcement (HOPE) probation when viewed through the lens of
therapeutic jurisprudence (TJ). The article commences with recent
conceptualizations of TJ through the metaphor and methodology of 'wine'/'liquid'
and 'bottles' (Wexler, 2014). Next, the article presents an overview of how HOPE
works and clarifies a number of misconceptions about the approach taken. The
article then examines the potential of the principles underlying HOPE to help in
realizing the promise of mainstreaming TJ. Specifically, it is argued that HOPE
is more economical than drug courts and can reach far more people. It addition,
it promotes procedural justice and desistance, is flexible and can be extended
across the criminal justice system.
PMID- 29958680
TI - On the systematic documentation of the structural characteristics of bovine
enamel: A critic to the protein sheath concept.
AB - The common structural description of bovine enamel used in materials science
studies - nano-sized hydroxyapatite crystallites form micron-sized prisms
surrounded by protein sheaths, which in turn build a complex decussation pattern
overlook many important morphological information. This hampers the correct
interpretation of the data determined by mechanical analysis. For a profound
structural description of enamel morphology, the visualization of its building
blocks by high-resolution electron microscopy and focused-ion beam tomography
technique, which reveals their form, orientation and configuration at different
regions of a tooth (cut in different directions), is undertaken in this work. We
adapted here the paleontological classification system and terminology developed
for the description of enamel microstructures seen in different species, and
accordingly documented the morphological singularities of bovine incisor enamel.
The appearance of the boundary regions between crystallites and prisms
contradicts to the well-known protein sheath concept. Neighboring crystallites
and prisms are not separated by prominent gap zones but they are largely in
contact with each other. Proteins might exist within the pores of 20-30nm in
size, which are distributed inhomogeneously through the boundary regions, rather
than as protein sheaths covering each crystallite and prism.
PMID- 29958681
TI - Semi-preparative high-resolution recycling liquid chromatography.
AB - A semi-preparative high-resolution system based on twin column recycling liquid
chromatography was built. The integrated system includes a binary pump mixer, a
sample manager, a two-column oven compartment, two low-dispersion detection
cells, and a fraction manager (analytical). It addresses challenges in
drug/impurity purification, which involve several constraints simultaneously: (1)
small selectivity factors (alpha < 1.2, poor resolution), (2) mismatch of elution
strength between the sample diluent and the eluent causing severe band fronting
or tailing, (3) diluent-to-eluent mismatch of viscosity causing viscous fingering
and unpredictable band deformation, (4) low abundance of the impurity relative to
the active pharmaceutical ingredient (API) (<1/100), and (5) yield and purity
levels to be larger than 99% and 90%, respectively. The prototype system was
tested for the preparation of a trace impurity present in a concentrated solution
of an API, estradiol. The ultimate goal was to collect ~1 mg of impurity (>90%
purity) for unambiguous structure elucidation by liquid state nuclear magnetic
resonance (NMR 600 MHz and above). First, the particle size (3.5 MUm) used to
pack the 4.6 mm * 150 mm long twin columns is selected so that the speed
resolution of the recycling process is maximized at 4000 psi pressure drop. Next,
the production rate of the process is also maximized by determining the optimum
number (7) of cycles and the corresponding largest sample volume (160 MUL) to be
injected. Finally, the process is fully automated by programming the time events
related to (1) sample cleaning, (2) transfer of the targeted impurity from one to
the second twin column, and (3) impurity collection. The process was tested
without interruption during one week for the collection of a trace impurity
(alpha = 1.166, strong acetonitrile-methanol sample diluent, concentration ~2
mg/L) from a concentrated (10 g/L) stock solution (60 mL total) of estradiol. The
process enriches the impurity content relative to the API by about a factor
~5000. For the lack of a sufficient collected amount (~120 MUg only) of the pure
impurity (purity 50% only), NMR experiments could not provide reliable results.
Instead, the combination of LC-MS (single ion monitoring) and UV absorption
spectra (lambdamax shift) revealed that the targeted impurity was likely the low
abundant enol tautomeric form of the ketone estrone, a possible intermediate or
by-product of the synthesis reaction of estradiol.
PMID- 29958682
TI - A two-dimensional non-comprehensive reversed/normal phase high-performance liquid
chromatography/tandem mass spectrometry system for determination of limonene and
linalool hydroperoxides.
AB - A two-dimensional non-comprehensive high-performance liquid chromatographic
(HPLC) system coupled to electrospray ionization tandem mass spectrometry was
developed for the determination of skin allergenic hydroperoxides of limonene and
linalool. These compounds are some major components behind skin sensitization and
contact (skin) allergy to fragrances. Fragrance hydroperoxides usually occur in
complex compositions, often as constituents of the natural essential oils added
to a large number of commercial products. Their similarities to interfering
compounds, many with identical elemental composition, make the determination
difficult even when using selective detection methods like mass spectrometry. In
this work, a first-dimension chromatographic heart-cut isolation of the
hydroperoxides on a reversed-phase HPLC system was combined with a second
dimension normal-phase HPLC system for separation of the hydroperoxides. The
intersystem transfer was made by trapping the heart-cut fraction on a short
graphitized carbon column, exchanging the mobile phase and back-flushing the
hydroperoxides into the second dimension. Each analysis was performed within 60
min without any pretreatment, except dilution, prior to injection. The obtained
instrumental limits of detection (LODs) at a signal-to-noise ratio of 3 were
lower than 1.2 ng injected on column and method LODs were below 0.3 ppm. An after
shave product was shown to contain the highest concentrations of the measured
hydroperoxides, with 445 +/- 23 ppm of total linalool hydroperoxides. This level
is likely able to elicit skin reactions in already sensitized individuals.
PMID- 29958683
TI - Detection of seventy-two anabolic and androgenic steroids and/or their esters in
horse hair using ultra-high performance liquid chromatography-high resolution
mass spectrometry in multiplexed targeted MS2 mode and gas chromatography-tandem
mass spectrometry.
AB - Anabolic and androgenic steroids (AAS) are banned substances in both human and
equine sports. They are often administered intramuscularly to horses in
esterified forms for the purpose of extending their time of action. The authors'
laboratory has previously reported an UHPLC/HRMS method using quadrupole-Orbitrap
mass spectrometer in full scan and parallel reaction monitoring (PRM) mode for
the detection of 48 AAS and/or their esters in horse hair. However, two
injections were required due to the long duty cycle time. In this paper, an
UHPLC/HRMS method using multiplexed targeted MS2 mode was developed and validated
to improve the coverage to 65 AAS and/or their esters in a single injection. In
addition, a GC/MS/MS method in selected reaction monitoring (SRM) mode was
developed to screen for another seven AAS and/or their esters not adequately
covered by the UHPLC/HRMS method using the same sample extract after
derivatisation with pentafluoropropionic anhydride. The UHPLC/HRMS and GC/MS/MS
methods in combination allowed the detection of 72 AAS and/or their esters with
estimated limits of detection down to sub to low ppb levels with good interday
precision. Method applicability was demonstrated by the detection of boldione and
4-androstenedione in two out-of-competition hair samples and testosterone
propionate in a referee hair sample.
PMID- 29958684
TI - Anaesthetic aspects in the treatment of fragility fracture patients.
AB - As longevity increases globally, the number of older, frailer, comorbid patients
requiring fragility fracture surgery will increase. Fundamentally, anaesthesia
should aim to maintain these patients' pre-fracture cognitive and physiological
trajectories and facilitate early (ie day 1) postoperative recovery. This review
describes the 10 general principles of anaesthesia for fragility fracture surgery
that best achieve these aims: multidisciplinary care, 'getting it right first
time', timely surgery, standardisation, sympathetic anaesthesia, avoiding
ischaemia, sympathetic analgesia, re-enablement, data collection and training.
PMID- 29958685
TI - Clinical research in fragility fractures.
AB - The Fragility Fracture Network is coordinating international initiatives to
promote collaborative research, multidisciplinary care, and the secondary
prevention of fragility fractures. This review discusses the use of national
audit processes and the collection of common outcomes to facilitate research, as
well as the key role played by patient and public involvement, and strategies to
overcome research barriers.
PMID- 29958686
TI - Physiotherapy following fragility fractures.
AB - Physiotherapy can play a vital role in the pathway of care of people after
fragility fracture and includes interventions of early mobilisation and
prescription of structured exercise programmes for maximising functional recovery
and reducing the risk of falls and further fractures. Although the optimal nature
of physiotherapist interventions after hip and vertebral fracture requires
further investigation in large-scale trials, evidence supports the prescription
of high-intensity and extended exercise interventions. This article will overview
interventions in the acute and chronic phases after hip fractures, interventions
after vertebral fracture and the role of physiotherapy in the prevention of
further fractures.
PMID- 29958687
TI - Letter to Editor regarding the article by wang et al "Open reduction and internal
fixation in a one-stage anterior cruciate ligament reconstruction surgery for the
treatment of tibial plateau fractures: A case report and literature review".
PMID- 29958688
TI - Nursing care of fragility fracture patients.
AB - The challenge of caring for patients with fragility fractures is particularly
acute for nursing teams who are in short supply and work with patients following
fracture on a 24 h basis, coordinating as well as providing complex care. This
paper considers the role of nurses within the orthogeriatric team and highlights
the value of effective nursing care in patient outcomes. It explores the nature
of nursing for patients with fragility fracture with a focus on the provision of
safe and effective care and the coordination of care across the interdisciplinary
team. It also highlights the need for specific skills in orthopaedic and
geriatric nursing as well as specialist education.
PMID- 29958689
TI - Concurrent inflammatory myopathy and myasthenia gravis with or without thymic
pathology: A case series and literature review.
AB - OBJECTIVES: The association of myasthenia gravis (MG) and inflammatory myositis
(IM) is rare and typically only one of the diseases is present. The management of
the 2 diseases differs, therefore it is important to recognize the concomitant
presentation. Here, we report a case series of 7 patients with co-existing MG and
IM with review of the literature. METHOD: We identified 7 patients with
concurrent MG and IM who were followed at the Neuromuscular Disease Program at a
tertiary referral center in Vancouver, British Columbia from 2004 to 2017.
RESULT: All 7 patients had ocular or bulbar involvement as manifestation of MG.
Three patients had simultaneous onset of MG and IM, 2 of whom presented with
myasthenia crisis and fulminant myositis. In the other 4 patients, MG was the
initial presentation and IM occurred 3-11 years after MG. Among these 7 patients,
4 had underlying thymic pathology, including 2 with benign thymoma and 2 with
stage IV thymoma; all 4 patients had antibodies to acetylcholine receptor (AChR).
Of the 3 patients with no thymic pathology by imaging or histology, 2 had
positive AChR antibody titer. For treatment, the thymoma was resected and
chemotherapy was administered if appropriate. Additional immunosuppressive
therapies including high-dose glucocorticoid, intravenous immunoglobulin (IVIG),
methotrexate, mycophenolate, or cyclosporine were necessary to achieve remission.
Two patients with no thymoma had refractory MG and IM, and both responded to
rituximab. We also conducted a literature review on the clinical characteristics
and management of this condition, and compared the previously reported cases to
the patients in our series. CONCLUSION: This is one of the largest case series of
MG-IM overlap with or without thymic pathology. In this cohort, the 2 disease
entities can occur simultaneously, or one presents before the other. Most of the
patients responded well to steroid, acetylcholinesterase inhibitor, and
immunosuppressive agents. In very refractory cases, rituximab appeared to be
effective, which has not been reported for the treatment of this condition
before.
PMID- 29958690
TI - Corrigendum to "Pericytic mimicry in well-differentiated liposarcoma/atypical
lipomatous tumor" (Hum Pathol 2016;54:92-99).
PMID- 29958691
TI - Use of thoracic ultrasound by physiotherapists: a scoping review of the
literature.
AB - BACKGROUND: Use of diagnostic thoracic ultrasound (TUS) in medical professions to
examine the pleura, lung parenchyma and diaphragm is gaining in popularity,
however the ways in which physiotherapists are using TUS is unclear. OBJECTIVE:
The aim of this scoping review is to gain an understanding of the emerging
evidence base surrounding physiotherapy use of TUS to inform research and
clinical practice. DATA SOURCES: A systematic search was conducted of the
following databases: Cochrane, EPPI centre, PROSPERO, Medline, CINAHL, AMED,
EMBASE, HMIC, and BNI. STUDY SELECTION: Inclusion criteria: primary research
reporting the use of diagnostic TUS; a physiotherapist as part of the study
design or as the chief investigator; published in English. SYNTHESIS METHODS:
Data regarding demographics, design, type of conditions and anatomical structures
investigated and profession leading the TUS of included papers were compiled in a
tabular format. RESULTS: Of the 26 included papers, nine studied healthy
participants, four studied COPD and four studied critical care patients. Most
papers (n=23) involved scanning the diaphragm. In eight studies the
physiotherapist operated the TUS. LIMITATIONS: The paper selection process was
performed by one author; with no cross-checking by another individual.
CONCLUSION: Use of TUS by physiotherapists is an emerging area in both diaphragm
and lung diagnostics. A wide range of patient populations may benefit from
physiotherapists using TUS. Papers in this review are heterogeneous making any
generalisability difficult but does show its potential for varied uses. TUS is an
innovative skill in the hands of physiotherapists, but more research is needed.
PMID- 29958692
TI - Switching off the jitters: Dabigatran as a candidate approach to halt atrial
fibrillation?
PMID- 29958694
TI - Use of extracorporeal treatments in the management of poisonings.
AB - Historically, the clinical application of extracorporeal treatments (ECTRs), such
as hemodialysis or hemoperfusion, was first intended for poisoned patients. With
time, ECTRs were used almost indiscriminately to facilitate the elimination of
many poisons, albeit with uncertain clinical benefit. To determine the precise
role of ECTRs in poisoning situations, multiple variables need to be considered
including a careful risk assessment, the poison's characteristics including
toxicokinetics, alternative treatments, the patient's clinical status, and
intricacies of available ECTRs, all of which are reviewed in this article.
Recently, evidence-based and expert opinion-based recommendations from the EXTRIP
workgroup were also published to help minimize the knowledge gap in this area.
PMID- 29958693
TI - Intradermal active full-length DNA Abeta42 immunization via electroporation leads
to high anti-Abeta antibody levels in wild-type mice.
AB - Abeta immunotherapies with anti-Abeta antibody responses have high potential as
possible prevention treatment for Alzheimer's disease. We have previously shown
that active DNA Abeta1-42 immunization via gene gun delivery led to a non
inflammatory immune response resulting in decreased Abeta levels in brains of an
immunized AD mouse model. To make DNA vaccination more applicable for clinical
use, we used here intradermal electroporation. With fine tuning of the
electropulse parameters, high antibody levels and low levels of inflammatory
cytokines in the cellular immunoassays were observed. Full-length DNA Abeta1-42
immunization delivered via electroporation has potential to be used in the
clinical setting.
PMID- 29958695
TI - Alveolar hemorrhage associated with cocaine consumption.
AB - Cocaine is an illegal drug; its abuse and toxicity are a public health problem
due to its high morbidity and mortality. Cocaine can affect the cardiovascular,
central nervous and respiratory systems. The case of a 42-year-old male without
history of chronic or degenerative diseases, but previous cocaine consumption is
presented in this report. The patient is admitted to the Emergency Department
given that the clinical presentation included hemoptysis and dyspnea with mild to
minimal activity, which evolved to orthopnea. Advanced airway management was
required and supportive care at the Intensive Care Unit was provided. Imaging
studies showed evidence compatible with alveolar hemorrhage diagnosis. In search
of an autoimmune etiology, an antibody-screening panel was requested, reporting
negative results for autoimmune disorders. The patient management was based on
corticosteroid therapy and plasmapheresis to counter the persistent hemoptysis
and hemoglobin serum level decline. The management strategy was based on the
clinical suspicion of vasculitis and a torpid clinical evolution. Pulmonary
sepsis ensued, resulting in patient's death. The necropsy report describes the
primary cause of death as diffuse alveolar hemorrhage secondary to diffuse
alveolar injury. This case report presents the detailed clinical, imagining and
histopathological findings of a patient with alveolar hemorrhage secondary to
cocaine consumption, as well as a review of the literature.
PMID- 29958696
TI - [Adverse effects of hair care in users].
AB - The panoply of products used by hair care professionals to wash, dye, shape and
beautify hair is not entirely free from adverse events. Such effects consist
mainly of irritation dermatitis and allergic contact eczema affecting the scalp,
as well as the back and front of the neck, the forehead and periorbital areas,
and the cheeks. The most frequently cited allergens include paraphenylenediamine
(PPD) in hair dyes, glycerol monothioglycolate (GMTG) in acid perm lotions, and
ammonium persulphate in hair lighteners (the latter substance being responsible
primarily for contact urticaria). However, care should also be paid to other
allergens such as cocamidopropyl betaine among surfactants, as well as certain
components in hair formulations such as preservatives and fragrances (as well as
minoxidil, frequently used by patients).
PMID- 29958698
TI - New tricks for an ancient system: Physiological and pathological roles of
complement in the CNS.
AB - While the mechanisms underlying the functions of the complement system in the
central nervous system (CNS) and systemically, namely opsonization, chemotaxis,
membrane lysis, and regulation of inflammation are the same, the plethora of
functions that complement orchestrates in the central nervous system (CNS) is
complex. Strictly controlled expression of complement effector molecules,
regulators and receptors across the gamut of life stages (embryogenesis,
development and maturation, aging and disease) dictate fascinating contributions
for this ancient system. Furthermore, it is becoming apparent that complement
functions differ widely across distinct brain regions. This review provides a
comprehensive overview of the newly identified roles for complement in the brain,
including its roles in CNS development and function, during aging and in the
processes of neurodegeneration. The diversity and selectively of beneficial and
detrimental activities of complement, while challenging, should lead to precision
targeting of specific components to provide disease modifying treatments for
devastating psychiatric and neurodegenerative disorders that are still without
effective treatment.
PMID- 29958697
TI - Clearance kinetics of the VGF-derived neuropeptide TLQP-21.
AB - : TLQP-21 is a multifunctional neuropeptide and a promising new medicinal target
for cardiometabolic and neurological diseases. However, to date its clearance
kinetics and plasma stability have not been studied. The presence of four
arginine residues led us to hypothesize that its half-life is relatively short.
Conversely, its biological activities led us to hypothesize that the peptide is
still taken up by adipose tissues effectively. [125I]TLQP-21 was i.v.
administered in rats followed by chasing the plasma radioactivity and assessing
tissue uptake. Plasma stability was measured using LC-MS. In vivo lipolysis was
assessed by the palmitate rate of appearance. RESULTS: A small single i.v. dose
of [125I]TLQP-21 had a terminal half-life of 110 min with a terminal clearance
rate constant, kt, of 0.0063/min, and an initial half-life of 0.97 min with an
initial clearance rate constant, ki, of 0.71/min. The total net uptake by adipose
tissue accounts for 4.4% of the entire dose equivalent while the liver, pancreas
and adrenal gland showed higher uptake. Uptake by the brain was negligible,
suggesting that i.v.-injected peptide does not cross the blood-brain-barrier.
TLQP-21 sustained isoproterenol-stimulated lipolysis in vivo. Finally, TLQP-21
was rapidly degraded producing several N-terminal and central sequence fragments
after 10 and 60 min in plasma in vitro. This study investigated the clearance and
stability of TLQP-21 peptide for the first time. While its pro-lipolytic effect
supports and extends previous findings, its short half-life and sequential
cleavage in the plasma suggest strategies for chemical modifications in order to
enhance its stability and therapeutic efficacy.
PMID- 29958699
TI - Corrigendum to "Deferiprone attenuates inflammation and myocardial fibrosis in
diabetic cardiomyopathy rats" [Biochem. Biophys. Res. Commun. Volume 486, Issue
4, 13 May 2017, Pages 930-936].
PMID- 29958700
TI - Membrane bioreactors and electrochemical processes for treatment of wastewaters
containing heavy metal ions, organics, micropollutants and dyes: Recent
developments.
AB - Research and development activities on standalone systems of membrane bioreactors
and electrochemical reactors for wastewater treatment have been intensified
recently. However, several challenges are still being faced during the operation
of these reactors. The current challenges associated with the operation of
standalone MBR and electrochemical reactors include: membrane fouling in MBR, set
backs from operational errors and conditions, energy consumption in
electrochemical systems, high cost requirement, and the need for simplified
models. The advantage of this review is to present the most critical challenges
and opportunities. These challenges have necessitated the design of MBR
derivatives such as anaerobic MBR (AnMBR), osmotic MBR (OMBR), biofilm MBR (BF
MBR), membrane aerated biofilm reactor (MABR), and magnetically-enhanced systems.
Likewise, electrochemical reactors with different configurations such as
parallel, cylindrical, rotating impeller-electrode, packed bed, and moving
particle configurations have emerged. One of the most effective approaches
towards reducing energy consumption and membrane fouling rate is the integration
of MBR with low-voltage electrochemical processes in an electrically-enhanced
membrane bioreactor (eMBR). Meanwhile, research on eMBR modeling and sludge reuse
is limited. Future trends should focus on novel/fresh concepts such as
electrically-enhanced AnMBRs, electrically-enhanced OMBRs, and coupled systems
with microbial fuel cells to further improve energy efficiency and effluent
quality.
PMID- 29958701
TI - Induction of Labor for Psychiatric Indications: A Case Series and Literature
Review.
PMID- 29958702
TI - Evidence-based use of acetaminophen for hemodynamically significant ductus
arteriosus in preterm infants.
AB - While cyclooxygenase inhibitors have been the most common medications used to
facilitate earlier closure of patent ductus arteriosus in preterm infants,
adverse effects and variable efficacy have highlighted a need for alternative
options. Acetaminophen facilitates ductal closure via an alternate pathway of
prostaglandin inhibition. Despite treatment with high doses, toxicity is uncommon
in preterm infants, possibly due to immature hepatic metabolism. Pooled data from
randomized clinical trials of early treatment demonstrate that acetaminophen has
similar efficacy as cyclooxygenase inhibitors for PDA closure with a favorable
side effect profile and without any apparent increase in adverse neonatal
outcomes. Acetaminophen may therefore be an ideal first-line agent among
moderately and extremely preterm infants, though there is a paucity of data from
controlled trials regarding its use in infants at the border of viability
(gestation age <=25 weeks). Evidence from clinical studies of limited quality
supports acetaminophen treatment as rescue therapy for infants with persistent
PDA after unsuccessful cyclooxygenase inhibitor treatment, including those being
considered for surgical ligation.
PMID- 29958703
TI - Patent ductus arteriosus, its treatments, and the risks of pulmonary morbidity.
AB - A persistent left-to-right shunt through a patent ductus arteriosus (PDA)
increases the rate of hydrostatic fluid filtration into the lung's interstitium,
impairs pulmonary mechanics, and prolongs the need for mechanical ventilation. In
preclinical trials, pharmacologic PDA closure leads to improved alveolarization
and minimizes the impaired postnatal alveolar development that is the pathologic
hallmark of bronchopulmonary dysplasia (BPD). Although routine prophylactic
treatment of a PDA on the day of birth does not appear to offer any more
protection against BPD than delaying treatment for 2-3 days, recent evidence from
quality improvement trials suggests that early pharmacologic treatment decreases
the incidence of BPD compared with a treatment approach that exposes infants to a
moderate-to-large PDA shunt for the first 7-10 days after birth. After the first
week, routine pharmacologic treatment (compared with continued PDA exposure) no
longer appears to alter the course of BPD development. Evidence from
epidemiologic, preclinical, and randomized controlled trials demonstrate that
early ductus ligation is an independent risk factor for the development of BPD.
PMID- 29958704
TI - Embryonic development, luteal size and blood flow area, and concentrations of
PGF2alpha metabolite in dairy cows fed a diet enriched in polysaturated or
polyunsaturated fatty acid.
AB - The objective of this study was to examine effects of sunflower (SO) and palm oil
(PO) supplements in the diet on embryonic development, luteal size and blood flow
area, PGF2alpha metabolite (PGFM), and progesterone (P4) concentrations.
Prepartum cows (n = 42) were randomly assigned to one of three dietary treatments
(control, 4% PO, and 4% SO supplements). Animals were fed diets individually from
day 28 prepartum to day 111 postpartum. Luteal size and blood flow area were
determined throughout the estrous cycle by Doppler ultrasonography. Oocytes were
collected in three ovum pick-up sessions at 2 week intervals for the in vitro
embryo production. Oocyte characteristics and embryonic development were not
affected by dietary treatments. Cows fed 4% SO had a greater (P < 0.05)
concentration of PGFM from day 15 to day 35 postpartum than those cows fed 4% PO
and the control group. On day 11 of the estrous cycle (mid-luteal phase), serum
P4 concentrations (6.0 +/- 0.7, 5.7 +/- 0.5, and 4.7 +/- 0.6 ng/ml), luteal size
(7.0 +/- 0.2, 6.5 +/- 0.2, and 5.3 +/- 0.1 cm2) and luteal blood flow area (1.3
+/- 0.2, 1.2 +/- 0.1, and 0.9 +/- 0.1 cm2) were greater (P < 0.05) in cows fed 4%
SO and 4% PO than the control group, respectively. Thus, plant oil supplements in
diets affected luteal size and serum P4 and PGFM concentrations, but not early
embryonic development. Such changes in secretion of PGF2alpha and P4 indicate
that plant oil supplements during pre- and postpartum may alter uterine and
luteal functions.
PMID- 29958705
TI - [Bilateral uveitis associated with nivolumab therapy].
AB - Immune-related adverse events (IRAEs) are rare but serious adverse events that
may be associated with inhibitors of few immune control points. The purpose here
is to report the case of an inflammatory ocular disease, potentially linked to
the immunity and use of nivolumab, a new immunological agent used for the
treatment of a solid tumor. In spite of the involvement of this treatment in the
onset of inflammation, we must always seek another cause. It is possible to
continue this treatment by considering the benefit/risk balance for each patient.
Close collaboration between oncologists and ophthalmologists is necessary in the
diagnosis and rapid management of these IRAE ocular related to these new emerging
therapies.
PMID- 29958706
TI - Consumption of aged white wine modulates cardiovascular risk factors via
circulating endothelial progenitor cells and inflammatory biomarkers.
AB - BACKGROUND & AIMS: There is compelling evidence showing that moderate alcohol
consumption reduces cardiovascular risk factors related to atherosclerosis. The
aim of this study was to evaluate the effects of aged white wine (AWW) and gin on
circulating endothelial progenitor cells (EPC) and the expression of cell
adhesion molecules, inflammatory cytokines and chemokines related to
atherosclerosis in high cardiovascular risk subjects. METHODS: This was an open,
randomized, controlled, crossover study in 38 high-risk male volunteers between
55 and 80 years of age randomized to receive 30 g of ethanol/day as AWW or gin
during 3 weeks. We used the paired two-tailed t-test to compare differences in
outcome variables in response to each intervention. Carryover effects for the two
periods were evaluated comparing the outcome variables before the AWW and gin
interventions. RESULTS: Compared to gin, AWW intake was associated with a
significant 39.6% increase in EPCs. Expression of CD31 and CD40 in T-lymphocytes
and of CCR2 and CD36 in monocytes also decreased significantly after AWW intake.
In addition, compared to gin, AWW was associated with a significant decrease of
plasma pro-inflammatory biomarkers interleukin-8 and interleukin-18 and vascular
and intercellular adhesion molecules-1. Lfa-1, Mac-1, VLA4, CD40 and CD31
expression in monocytes and interferon gamma (IFN-gamma) concentrations
significantly decreased after intake of both alcoholic beverages. CONCLUSIONS:
AWW shows a greater ability to repair and maintain endothelial integrity compared
to gin. This effect is probably due to grape-derived minor components in AWW,
which are absent in gin.
PMID- 29958707
TI - Missed opportunities within the health system for the diagnosis of HIV infection
in MSM in Spain: Greater commitment and action is required.
PMID- 29958708
TI - Emergency Medical Services Simple Thoracostomy for Traumatic Cardiac Arrest:
Postimplementation Experience in a Ground-based Suburban/Rural Emergency Medical
Services Agency.
AB - BACKGROUND: Tube thoracostomy has long been the standard of care for treatment of
tension pneumothorax in the hospital setting yet is uncommon in prehospital care
apart from helicopter emergency medical services. OBJECTIVE: We aimed to evaluate
the performance of simple thoracostomy (ST) for patients with traumatic cardiac
arrest and suspected tension pneumothorax. METHODS: We conducted a retrospective
case series of consecutive patients with traumatic cardiac arrest where simple
thoracostomy was used during the resuscitation effort. Data were abstracted from
our Zoll emergency medical record (Zoll Medical Corp., Chelmsford, MA) for
patients who received the procedure between June 1, 2013 and July 1, 2017. We
collected general descriptive characteristics, procedural success, presence of
air or blood, and outcomes for each patient. RESULTS: During the study period we
performed ST on 57 patients. The mean age was 41 years old (range 15-81 years
old) and 83% were male. Indications included 40 of 57 (70%) blunt trauma and 17
of 57 (30%) penetrating trauma. The presenting rhythm was pulseless electrical
activity 65%, asystole 26%, ventricular tachycardia/fibrillation 4%, and
nonrecorded 5%. Eighteen of 57 (32%) had air return, 14 of 57 (25%) return of
spontaneous circulation, with 6 of 57 (11%) surviving to 24 h and 4 of 57 (7%)
discharged from the hospital neurologically intact. Of the survivors, all were
blunt trauma mechanism with initial rhythms of pulseless electrical activity.
There were no reported medic injuries. CONCLUSIONS: Our data show that properly
trained paramedics in ground-based emergency medical services were able to safely
and effectively perform ST in patients with traumatic cardiac arrest. We found a
significant (32%) presence of pneumothorax in our sample, which supports
previously reported high rates in this patient population.
PMID- 29958709
TI - Meta-Analysis Comparing Outcomes and Need for Renal Replacement Therapy of
Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement.
AB - Acute kidney injury (AKI) is commonly associated with aortic valve replacement.
Surgical aortic valve replacement (SAVR) is a known risk factor for AKI but
little is known about the short- and long-term effects of transcatheter aortic
valve implantation (TAVI). The purpose of our analysis is to identify the short-
and long-term effect of TAVI on renal outcomes. We searched Medline and PUBMED
from January 1, 2000 to November 6, 2017 for randomized control trials (RCTs)
comparing TAVI to SAVR in patients with severe aortic stenosis. Three hundred
sixty-nine trials were identified, 6 RCTs were included in our analysis. RevMan
version 5.3 was used for statistical analysis. Heterogeneity is calculated using
I2 statistics. Primary outcomes were AKI within 30 days and 1 year of TAVI, and
requirement for renal replacement therapy. We included 5,536 patients (2,796 in
TAVI and 2,740 in SAVR arm) from 6 RCTs. Baseline characteristics were similar.
There was reduced incidence of AKI at 30 days of TAVI compared with SAVR, 57
versus 133 (odds ratio [OR] 0.40, confidence interval [CI] 0.28 to 0.56, p
<0.00001, I2 = 7%) with no difference at 1 year (OR 0.65, CI 0.32 to 1.32, p =
0.23, I2 = 76%) and need for renal replacement therapy OR 0.95, CI 0.50 to 1.80,
p = 0.87, I2 = 0%). Permanent pacemaker was more frequent in the TAVI arm
compared with SAVR arm, 379 versus 110, (OR 3.75, CI 1.67 to 8.42, p = 0.001, I2
= 89%). In conclusion, TAVI is associated with a reduction in AKIs at 30 days
despite the exposure to contrast and higher incidence of new permanent pacemaker
placement.
PMID- 29958710
TI - Concomitant Associations of Healthy Food Intake and Cardiorespiratory Fitness
With Coronary Artery Calcium.
AB - Conflicting findings remain regarding associations between lifestyle behaviors
and coronary artery calcium (CAC). We investigated concomitant associations of
healthy food intake and cardiorespiratory fitness (CRF) with CAC. Data from 706
men and women 50 to 64 years old from the Swedish SCAPIS pilot trial were
analyzed. A CAC score was calculated using the Agatston method. A Healthy Food
Index (HFI) was established using data from a web-based food frequency
questionnaire. CRF was assessed from a bike exercise test. Regression analyses
were performed with occurrence of CAC (dichotomous) and level of CAC score in
patients with CAC (continuous) as outcomes. 58% had 0 CAC score. HFI was
significantly associated with having no CAC (standardized coefficient beta =
0.18, p <0.001) but not with level of CAC score (beta = -0.09, p = 0.34). CRF
showed no significant association with having no CAC (beta = -0.08, p = 0.12) or
with the level of CAC score (beta = -0.04, p = 0.64). However, there was an
interaction between HFI and CRF (beta = -0.23, p = 0.02); for increasing levels
of CRF there was stronger negative association between HFI and level of CAC
score, reaching beta = -0.48, p = 0.045 for the highest CRF level. In conclusion,
these results emphasize the importance of a healthy food intake in combination
with higher CRF to counteract CAC development.
PMID- 29958711
TI - Usefulness of Addition of Magnetic Resonance Imaging to Echocardiographic Imaging
to Predict Left Ventricular Reverse Remodeling in Patients With Nonischemic
Cardiomyopathy.
AB - Defining short-term prognosis in nonischemic cardiomyopathy (NICM) is challenging
in clinical practice. Although left ventricular reverse remodeling (LVRR) is a
key prognostic marker in NICM there are few parameters able to predict it. We
investigated whether a complete structural and functional cardiac magnetic
resonance imaging (cMRI) evaluation was incremental to the classic clinical
echocardiographic approach in predicting LVRR in a large cohort of NICM patients
receiving evidence-based treatment. Patients with a recent diagnosis of NICM (<3
months) who underwent complete clinical, echocardiographic and cMRI assessment
were consecutively enrolled from 2008 to 2016. LVRR was defined as an increase in
>=10 points or normalization of left ventricular ejection fraction, associated
with a >=10% reduction or normalization of left ventricular end-diastolic
diameter at midterm (median time 20 months) echocardiographic follow-up. Among 80
NICM patients included in the study, LVRR was observed in 43 (54%). At
multivariate analysis, the clinical-echocardiographic evaluation failed to
identify independent predictors of LVRR. However, absence of late gadolinium
enhancement (odds ratio [OR] 9.07; confidence interval [CI] 2.7 to 13.1; p value
0.0003), left ventricular mass (OR 1.018; CI 1.001 to 1.036; p value 0.045) and
peak circumferential strain (OR 1.213; CI 1.011 to 1.470; p value 0.049) assessed
by cMRI were independently associated with LVRR. A model for LVRR prediction
based on cMRI and clinical-echocardiographic parameters performed significantly
better than the clinical-echocardiographic model alone (area under curve 0.84 vs
0.72; p value 0.023). In conclusion, an integrated imaging approach with the
addition of a structural and functional cMRI study to the standard-of-care
evaluation improves the prediction of LVRR in a large cohort of patients with
recently diagnosed NICM receiving evidence-based treatment.
PMID- 29958712
TI - Echocardiography in Patients With Infective Endocarditis and the Impact of
Diagnostic Delays on Clinical Outcomes.
AB - Infective endocarditis (IE) is associated with high mortality and morbidity. The
aim of this study was to investigate the impact of timing of echocardiography on
IE complications. We studied 151 consecutive patients with definite IE. Valve
destruction was defined as >=1 of severe regurgitation, cardiac abscess, or
fistula. A definitive echocardiogram was the first echocardiogram (transthoracic
(TTE) or Transesophageal (TEE)) which identified pathology consistent with IE and
further echocardiography was not required for the diagnosis. TTE and TEE were
performed within 4 days of admission in 62% and 15% patients respectively.
Definitive echocardiography was achieved with TTE in 60% patients and required
additional TEE in 40% patients. Significantly more in-patient embolic events
occurred when definitive echocardiography was performed late (>=4 days) compared
with early (<4 days) (40% vs 14%, p = 0.043). A significantly greater proportion
of patients who underwent late definitive echocardiography (>=4 days) required
valve surgery (73% vs 56%, p = 0.04). Time to definitive echocardiography (odds
ratio [OR] 1.015, p = 0.011), male gender (OR 1.254, p = 0.005) and age (OR
0.992, p = 0.002) were predictors of severe valve destruction. Late definitive
echocardiography (OR 1.166, p=0.035) was a predictor of in-patient embolism. In
conclusion, time to definitive echocardiography is an important predictor of
valve destruction, embolic events, and subsequent valve surgery. Pathways to
reduce delays to echocardiography are required in patients with suspected IE.
PMID- 29958713
TI - Differences in Heart Rate Response and Recovery After 6-Minute Walk Test Between
Patients With Atrial Fibrillation and in Sinus Rhythm.
AB - Long-term heart rate (HR) control is a management strategy for patients with
chronic atrial fibrillation (AF). Nevertheless, the optimal target HR of AF
patients is debatable. Our aim was to study HR at rest, during, and after a 6
minute walk test (6MWT) in AF patients, compared with controls with sinus rhythm
(SR). Consecutive matched patients with AF (n = 186) or SR (n = 172) were
recruited, and 6MWT was performed. HRs at rest, during 6MWT, and recovery periods
were recorded. All subjects were divided into 5 subgroups (<80 beats/min, 80 to
89 beats/min, 90 to 99 beats/min, 100 to 109 beats/min, and >=110 beats/min)
according to the HR at rest. No statistical difference was observed in baseline
HR at rest, between AF and SR groups (p = 0.30). The exercise HR increase
percentage was significantly higher in overall AF patients compared with those in
SR (40 +/- 15% vs 14 +/- 7%, p <0.001). Even with similar mean baseline HRs at
rest, the 5 AF subgroups all showed significantly higher mean exercise HR,
maximal exercise HR, and maximal exercise HR increase percentage compared with
their respective SR subgroups, especially the subgroups with HR at rest >90
beats/min. Unlike the SR patients, the 4 AF subgroups with HR >80 beats/min at
the fifth minute after 6MWT did not recover to at rest levels. In conclusion, HR
increased excessively during 6MWT and HR recovery was delayed after 6MWT in AF
patients, especially when HR at rest is >90 beats/min. The optimal initial HR at
rest for AF patients should perhaps be <90 beats/min.
PMID- 29958714
TI - Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy
on the Progression of Atrial Fibrillation (from the Euro Heart Survey).
AB - Hypertension is a risk factor for both progression of atrial fibrillation (AF)
and development of AF-related complications, that is major adverse cardiac and
cerebrovascular events (MACCE). It is unknown whether left ventricular
hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both
these end points. We aimed to assess this in low-risk AF patients, also assessing
gender-related differences. We included 799 patients from the Euro Heart Survey
with nonvalvular AF and a baseline echocardiogram. Patients with and without
hypertension were included. End points after 1 year were occurrence of AF
progression, that is paroxysmal AF becoming persistent and/or permanent AF, and
MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF
progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up.
In hypertensive patients with LVH, AF progression occurred more frequently as
compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In
hypertensive AF patients, LVH was the most important multivariably adjusted
determinant of AF progression on multivariable logistic regression (odds ratio
4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only
seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive
patients, no differences were found in AF progression rates regarding the
presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen
in MACCE for hypertensive patients with and without LVH. In conclusion, in men
with hypertension, LVH is associated with AF progression. This association seems
to be absent in hypertensive women.
PMID- 29958715
TI - Clinical Impact of ABO and Rhesus D Blood Type Groups in Patients With Chronic
Heart Failure.
AB - Blood group systems based on red blood cell antigens are genetically determined
and can identify patients at risk. Type non-O of the ABO blood group system has
been associated with coronary artery disease, thrombosis, and a worse prognosis.
The present study evaluated the distribution of blood group types in patients
with heart failure (HF) and the impact on clinical outcome. We evaluated the ABO
and Rhesus D antigen (RhD) blood types in a large cohort of chronic HF patients
(n = 3,815). ABO blood type distribution in the HF population was not
significantly different to that reported in the general national population (A
40%, B 20%, AB 8%, and O 33%). The percentage of Rh-negative per blood type was
also similar (A 10%, B 9%, AB 10%, and O 7%). Patients with type O were more
likely to be hypertensive compared with non-O type. Mean follow-up was 4.2 years.
Overall survival during follow-up was 55%. Cox regression analysis after
adjustment for significant predictors demonstrated that RhD-negative was
associated with a worse prognosis in patients with ischemic cardiomyopathy (n =
2,881, 76%): hazard ratio 1.26, 95% confidence interval 1.04 to 1.53, p = 0.02.
Type non-O was also independently associated with a worse prognosis compared with
type O in patients with non-ischemic cardiomyopathy: hazard ratio 1.32, 95%
confidence interval 1.04 to 1.67, p = 0.02. In conclusion, blood group type
distribution in HF patients are similar to the general population. RhD-negative
is associated with a worse prognosis in patients with ischemic cardiomyopathy.
PMID- 29958716
TI - A comprehensive review of signal peptides: Structure, roles, and applications.
AB - Signal peptides (SP) are short peptides located in the N-terminal of proteins,
carrying information for protein secretion. They are ubiquitous to all
prokaryotes and eukaryotes. SPs have been of special interest in several
scientific and industrial fields, including recombinant protein production,
disease diagnosis, immunization, and laboratory techniques. Recently, the role of
SPs in recombinant protein production has gained too much attention. Herein,
several studies have been reviewed to elucidate the precise structure and
function of SPs, particularly the optimized ones for recombinant protein
production. However, some features of SPs still have remained obscure. In this
review, some approaches concerning elucidation and optimization of SPs are
discussed, and pragmatic conclusions and suggestions for future studies are also
proposed. Moreover, a summary of secretory pathways, evolutionary changes,
functions, applications, and different types of SPs is mentioned. At last,
current limitations and prospects are discussed.
PMID- 29958717
TI - [Gynecological management and follow-up in women with cystic fibrosis].
AB - INTRODUCTION: Most women with cystic fibrosis reach adulthood and should have
appropriate gynecological follow-up and contraception. BACKGROUND: There is no
specific contra-indication to any contraception due to cystic fibrosis itself.
Combined estrogen-progesterone contraception can be used in most cases (including
transplanted women). In case of transplantation, intra-uterine devices should be
used carefully (risk of pelvic inflammatory disease, potential risk of
contraceptive failure with copper intra-uterine devices). Hormonal contraceptives
may not be effective in women taking corrective treatments aiming to correct the
maturation defect of the chloride channel. Screening for cervical cancer is
recommended with a pap smear every three years for women aged 25-65, but yearly
and starting at a younger age among transplanted women who are at higher risk for
cervical dysplasia. Human Papillomavirus vaccination should be offered to all
young women. OUTLOOK: Women with cystic fibrosis and health care providers should
be better informed on screening and on sexual and reproductive health to avoid
unplanned pregnancies, to take into account drug interactions and to prevent
cervical disease. CONCLUSION: Regular and specific gynecological management is
mandatory in cases of cystic fibrosis.
PMID- 29958718
TI - Isolating infectious patients: organizational, clinical, and ethical issues.
AB - BACKGROUND: Isolating infectious patients is essential to reduce infection risk.
Effectiveness depends on identifying infectious patients, transferring them to
suitable accommodations, and maintaining precautions. METHODS: Online study to
address identification of infectious patients, transfer, and challenges of
maintaining isolation in hospitals in the United Kingdom. RESULTS: Forty-nine
responses were obtained. Decision to isolate is made by infection prevention
teams, clinicians, and managers. Respondents reported situations where isolation
was impossible because of the patient's physical condition or cognitive status.
Very sick patients and those with dementia were not thought to tolerate isolation
well. Patients were informed about the need for isolation by ward nurses,
sometimes with explanations from infection prevention teams. Explanations were
often poorly received and comprehended, resulting in complaints. Respondents were
aware of ethical dilemmas associated with isolation that is undertaken in the
interests of other health service users and society. Organizational failures
could delay initaiting isolation. Records were kept of the demand for isolation
and/or uptake, but quality was variable. CONCLUSION: Isolation has received the
most attention in countries with under-provision of accommodations. Our study
characterizes reasons for delays in identifying patients and failures of
isolation, which place others at risk and which apply to any organization
regardless of availability. It also highlights the ethical dilemmas of enforcing
isolation.
PMID- 29958719
TI - Trends in Cardiovascular Disease Risk in the U.S., 1999-2014.
AB - INTRODUCTION: Cardiovascular disease is the leading cause of death in the U.S.
and national prevalence of the proportion of individuals at high risk is unknown.
The objective of this study was to investigate the prevalence and trends in high
cardiovascular disease risk among adults in the U.S. METHODS: In 2017, the
authors performed a cross-sectional analysis of data from the National Health and
Nutrition Examination Survey, 1999-2014 for adults aged 40-79 years without a
diagnosis of cardiovascular disease (unweighted n=18,269, weighted n=96,512,989).
The American College of Cardiology/American Heart Association Atherosclerotic
Cardiovascular Disease risk score was calculated for all participants with
complete data. Change in prevalence of individuals at high risk of cardiovascular
disease was assessed, defined as >=7.5% 10-year risk and >=20% 10-year risk.
RESULTS: The prevalence of high risk level did not significantly change over time
for the entire sample using the 7.5% 10-year risk level, but did decline
significantly at 20% 10-year risk level. Logistic regression results showed that
prevalence among non-Hispanic black males increased significantly from 53.5% in
1999-2002 to 65.2% in 2011-2014 using the 7.5% 10-year risk cut off (p
trend=0.003). CONCLUSIONS: A substantial proportion of the population is at high
risk of cardiovascular disease. Prevalence of high-risk individuals is prominent
for non-Hispanic black males; the reasons for which are unclear. Public health
efforts to increase awareness should be considered for this vulnerable
population.
PMID- 29958720
TI - Extended total temporomandibular joint replacements: a classification system.
AB - Prosthetic total temporomandibular joint (TMJ) replacement (TJR) is well
established in the United Kingdom, with clear guidelines for indications and
nationally published outcomes. CAD/CAM technology has made it possible to push
the boundaries of custom-made TJR to include extended versions (eTJR), which may
replace segmental mandibular defects or defects in the skull base with extended
components for the ramus and fossa, respectively. Such prostheses are uncommon,
and published reports are restricted to isolated cases and series of cases. We
know of no previous attempts to classify such prostheses, and here we suggest a
bipartite classification system for use in communications between surgeons and
manufacturers based on a review of 19 prostheses provided by one manufacturer
(TMJ Concepts, Ventura, CA).
PMID- 29958722
TI - A review of disability EEG based wheelchair control system: Coherent taxonomy,
open challenges and recommendations.
AB - CONTEXT: Intelligent wheelchair technology has recently been utilised to address
several mobility problems. Techniques based on brain-computer interface (BCI) are
currently used to develop electric wheelchairs. Using human brain control in
wheelchairs for people with disability has elicited widespread attention due to
its flexibility. OBJECTIVE: This study aims to determine the background of recent
studies on wheelchair control based on BCI for disability and map the literature
survey into a coherent taxonomy. The study intends to identify the most important
aspects in this emerging field as an impetus for using BCI for disability in
electric-powered wheelchair (EPW) control, which remains a challenge. The study
also attempts to provide recommendations for solving other existing limitations
and challenges. METHODS: We systematically searched all articles about EPW
control based on BCI for disability in three popular databases: ScienceDirect,
IEEE and Web of Science. These databases contain numerous articles that
considerably influenced this field and cover most of the relevant theoretical and
technical issues. RESULTS: We selected 100 articles on the basis of our inclusion
and exclusion criteria. A large set of articles (55) discussed on developing real
time wheelchair control systems based on BCI for disability signals. Another set
of articles (25) focused on analysing BCI for disability signals for wheelchair
control. The third set of articles (14) considered the simulation of wheelchair
control based on BCI for disability signals. Four articles designed a framework
for wheelchair control based on BCI for disability signals. Finally, one article
reviewed concerns regarding wheelchair control based on BCI for disability
signals. DISCUSSION: Since 2007, researchers have pursued the possibility of
using BCI for disability in EPW control through different approaches. Regardless
of type, articles have focused on addressing limitations that impede the full
efficiency of BCI for disability and recommended solutions for these limitations.
CONCLUSIONS: Studies on wheelchair control based on BCI for disability
considerably influence society due to the large number of people with disability.
Therefore, we aim to provide researchers and developers with a clear
understanding of this platform and highlight the challenges and gaps in the
current and future studies.
PMID- 29958721
TI - Disparities in Perioperative Radiation Therapy Use in Elderly Patients With Soft
Tissue Sarcoma.
AB - PURPOSE: The benefit of perioperative radiation therapy in elderly patients with
soft-tissue sarcoma (STS) is unclear due to the underrepresentation of elderly
patients in clinical trials. We assessed patterns of care and overall survival
(OS) associated with perioperative radiation therapy use in this population.
METHODS AND MATERIALS: Elderly patients (>=70 years) with high-grade STS who
underwent surgery with or without perioperative radiation therapy from 2004 to
2013 were identified from the National Cancer Database. A nonelderly cohort (<70
years) was also identified for secondary comparative analyses. The association
between perioperative radiation therapy use and OS was assessed using propensity
score-weighted Cox proportional hazards analyses. Relative survival was
calculated using national life tables to assess the impact of radiation therapy
on estimated sarcoma-specific survival in elderly and nonelderly patients.
Patterns of care were assessed using multivariable logistic regression analyses.
RESULTS: Of 6978 elderly patients, 3549 (51%) underwent surgery alone, and 740
(11%) and 2,679 (38%) received pre- and postoperative radiation therapy,
respectively. Elderly patients received radiation therapy less commonly than did
nonelderly patients (49% vs 52%, P < .001) despite presenting with higher grade
tumors (grade 3, 86% vs 80%, P < .001) and experiencing more frequent positive
surgical margins (23% vs 16%, P < .001). On propensity score-weighted analyses,
preoperative (hazard ratio = 0.64, 95% confidence interval: 0.54-0.77, P < .001)
and postoperative (hazard ratio = 0.72, 95% confidence interval: 0.67-0.77, P <
.001) radiation therapy use was associated with improved OS compared with surgery
alone. These associations were robust to landmark analyses of patients surviving
at least 12 months. Radiation therapy use resulted in a greater magnitude of 5
year relative survival improvement in elderly than nonelderly patients.
CONCLUSIONS: There is an overall and an age-disparate underuse of perioperative
radiation therapy in elderly patients with high-grade STS despite radiation
therapy being associated with improved OS. Further research is warranted to
minimize gaps in care for elderly patients.
PMID- 29958723
TI - The sex ratio at birth after recent major earthquakes in Japan.
PMID- 29958724
TI - Corynebacterium heidelbergense sp. nov., isolated from the preen glands of
Egyptian geese (Alopochen aegyptiacus).
AB - Two strains (pedersoliT and girotti) of a new species of bacteria were isolated
from the preen glands of wild Egyptian geese (Alopochen aegyptiacus) from the
river Neckar in southern Germany in two subsequent years. The strains were
lipophilic, fastidious, Gram-positive rods and belonged to the genus
Corynebacterium. Phylogenetically, the isolates were most closely related to
Corynebacterium falsenii DSM 44353T which has been found to be associated with
birds before. 16S rRNA gene sequence similarity to all known Corynebacterium spp.
was significantly <97%. Corresponding values of rpoB showed low levels of
similarity <87% and ANIb was <73%. G+C content of the genomic DNA was 65.0mol%
for the type strain of the goose isolates, as opposed to 63.2mol% in
Corynebacterium falsenii. MALDI-TOF MS analysis of the whole-cell proteins
revealed patterns clearly different from the related species, as did biochemical
tests, and polar lipid profiles. We therefore conclude that the avian isolates
constitute strains of a new species, for which the name Corynebacterium
heidelbergense sp. nov. is proposed. The type strain is pedersoliT (=DSM
104638T=LMG 30044T).
PMID- 29958725
TI - Out-of-Hospital Cardiac Arrest in the Presence of Ischemic Heart Disease: What Is
the Long-term Arrhythmic Risk After Revascularization?
AB - Patients resuscitated from out-of-hospital cardiac arrest (OHCA) frequently have
underlying coronary artery disease (CAD), but the relationship between the arrest
and myocardial ischemia or infarction due to CAD can be difficult to discern in
clinical practice. Patients often present with clinical profiles that guideline
recommendations for appropriate implantable cardioverter-defibrillator use do not
address. In cases of incomplete revascularization or mild but sustained
impairment of ventricular function, it is not clear if the cause of the cardiac
arrest is completely "reversible." We describe distinct phenotypes of patients
with OHCA and concomitant CAD and highlight current knowledge gaps in their
management and outcomes.
PMID- 29958726
TI - Scapular muscles strengthening on pain, functional outcome and muscle activity in
chronic lateral epicondylalgia.
AB - AIM: The aim of the study was to investigate the effect of lower trapezius (LT),
middle trapezius (MT) and serratus anterior (SA) strengthening on pain, pain free
grip strength, functional outcome, scapular muscles strength, scapular position
and electromyographic (EMG) activity of lower trapezius, serratus anterior,
extensor carpi radialis brevis (ECRB) and extensor digitorum communis (EDC) in
individuals with chronic lateral epicondylalgia (LE). METHODS: Twenty six
patients with chronic lateral epicondylalgia were recruited. Subjects were
divided into two groups. Group 1 received scapular muscles strengthening along
with conventional physiotherapy and Group 2 received only conventional
physiotherapy for 6 weeks. Subjects were measured for pain (VAS), pain free grip
strength, functional outcome (PRTEE), scapular muscle strength, scapular
positioning (LSST) and EMG activity before and after the intervention.2 * 2 mixed
ANOVA was used to investigate for main effect of time and group and interaction
effect (time * group). RESULTS: The results revealed that there was statistically
significant difference for time effect for all the outcome measures. In time *
group interaction there was significant difference for all the outcome measures
except scapular position (LSST3). Significant difference for group effect was
observed in EMG activity of LT and ECRB. CONCLUSION: The scapular muscle
strengthening should be used along with the conventional physiotherapy in
individuals with chronic LE to improve pain, pain free grip strength, functional
outcome, muscle strength, scapular position and muscle activity.
PMID- 29958727
TI - miR-200c inhibits the arecoline-associated myofibroblastic transdifferentiation
in buccal mucosal fibroblasts.
AB - BACKGROUND/PURPOSE: MicroRNA-200c (miR-200c) recently emerged as an important
regulator of tumorigenesis and cancer metastasis, however, its role in regulating
oral submucous fibrosis (OSF) remains unknown. In this study, we investigated the
functional role of miR-200c in myofibroblastic differentiation activity and
identified its potential target. METHODS: qRT-PCR was applied to assess the
expression of miR-200c in OSF tissues and fibrotic buccal mucosal fibroblasts
(fBMFs). Arecoline, a major areca nut alkaloid, was utilized to explore whether
the expression of miR-200c would alter following stimulation. Collagen gel
contraction, migration and invasion capabilities were examined in arecoline
stimulated BMFs as wells as in fBMFs. Luciferase reporter assay was conducted to
show the relationship between miR-200c and ZEB1. RESULTS: Our results showed that
the expression of miR-200c was downregulated in OSF specimen and fBMFs. Arecoline
treatment dose-dependently reduced the relative expression of miR-200c in normal
BMFs. Overexpression of miR-200c impeded the arecoline-induced collagen gel
contraction, migration, invasion and wound healing capacities. Moreover, ectopic
expression of miR-200c in fBMFs successfully reduced the increased collagen gel
contractility and invasion abilities. Our results demonstrated that ZEB1 was a
direct target of miR-200c, and overexpression of miR-200c inhibited the
expression of ZEB1 and alpha-SMA. CONCLUSION: These findings suggest that
downregulation of miR-200c in OSF may be involved in the pathogenesis of areca
nut-associated OSF through regulation of ZEB1.
PMID- 29958728
TI - Chyle leak after pancreatic surgery: validation of the International Study Group
of Pancreatic Surgery classification.
AB - BACKGROUND: Chyle leak is an uncommon complication after pancreatic surgery. The
chyle leak incidence, definition, diagnosis, and treatment had been reported
heterogeneously so far. Recently a consensus definition and grading system was
published by the International Study Group for Pancreatic Surgery. This study
aims to evaluate the differences in the clinical and economic burden of chyle
leak applying the new definition. METHODS: All data from patients who underwent
pancreatic surgery for any disease from January 2014 to December 2016 were
retrieved from the institutional prospective database. The 2017 International
Study Group for Pancreatic Surgery definition and classification were applied.
The classification was validated analyzing the differences in major
complications, length of stay, and hospitalization costs. RESULTS: A total of 945
patients was the final population. A chyle leak was reported in 43 patients
(4.5%). Grade A chyle leak occurred in 10 patients (23.3%), Grade B chyle leak in
31 patients (72.1%), and Grade C chyle leak in 2 patients (4.6%). Chyle leak
occurred as unique postoperative complication in 29 cases (67.4%). The economic
analysis showed that the average costs of the 3 grades were 2,806, 7,150 and
15,684 euros respectively (P < .001). Furthermore, the length of stay, the rates
of septic events, and major complications were significantly different among the
3 grades (P = .008, P = .004, and P < .001, respectively). Of note, we did not
find any intraoperative factor associated with chyle leak. CONCLUSION: The
present study confirms the validity of the International Study Group for
Pancreatic Surgery classification of chyle leak. The 3 grades of chyle leak
proposed identify reliably clinical and economical differences among the chyle
leak cases.
PMID- 29958729
TI - Establishment of the National Consortium for Regenerative Medicine and National
Regenerative Medicine Database in Japan.
AB - With its aim to regain the function of organs that are damaged by illness or
injury, regenerative medicine has become the global focus of research. To
accelerate the development and establishment of sufficient safety measures in
regenerative medicine in Japan, the Pharmaceuticals and Medical Devices Act and
the Act on Safety of Regenerative Medicine were enacted in 2014. Advancements in
regenerative medicine are anticipated to draw attention toward the development of
a system that consolidates and uses valuable data from studies performed from
premarketing to postmarketing stages. Data gathered from premarketing to
postmarketing stages of clinical research would promote new development avenues
that would lead to the establishment of appropriate evaluation methods for new
regenerative medical products by data validation. Against this background, the
Japanese Society for Regenerative Medicine has been working to establish a
national consortium for promoting regenerative medicine and constructing a large
scale clinical data registry, called the National Regenerative Medicine Database.
This article aims to introduce the current framework of regenerative medicine in
Japan, with a particular focus on the activity for establishment of a national
consortium for regenerative medicine and the National Regenerative Medicine
Database.
PMID- 29958730
TI - Molecular dissection of large cell carcinomas of the lung with null
immunophenotype.
AB - The aim of this study was to subcategorise large cell carcinoma (LCC) with null
immunophenotype according to the World Health Organization (WHO) Classification
of 2015 into the existing groups of adenocarcinoma and squamous cell carcinoma by
further molecular genetic analysis. Lineage-specific molecular alterations of
these tumours could depict additional therapeutic approaches. We analysed a
cohort of 35 LCC diagnosed according to the 2004 WHO classification and
reclassified them according to the criteria of the 2015 WHO classification.
Subsequently, tumours with a null immunophenotype were analysed by targeted next
generation sequencing (42 marker genes including TP53, EGFR, KRAS, STK11 and
SMARC4A) and fluorescence in situ hybridisation (ROS1, ALK). By applying the
criteria of the 2015 WHO classification and subsequent molecular subtyping we
could show that out of 35 previously diagnosed LCC, 16 cases could be
reclassified into specific NSCLC subtypes using immunohistochemistry.
Additionally, based on their mutational pattern, eight of the remaining 19 cases
with null immunophenotype could be assigned as 'favour adenocarcinoma'. We
demonstrate that molecular subtyping is helpful to further categorise LCC with
null immunophenotype. Our findings argue for an algorithm including stratified
molecular analysis of all respective cases.
PMID- 29958731
TI - Lipofibromatosis-like neural tumour: a clinicopathological study of ten
additional cases of an emerging novel entity.
AB - We present our experience with ten cases of lipofibromatosis-like tumour (LPF-NT)
to further characterise this newly described neoplasm. There were six males and
four females with a mean age of 12.8 years (range 2-37 years). Tumours occurred
in the neck (n = 3), buttock (n = 2), chest wall, flank, hip, hand and foot (n =
1). Histologically, they were composed of cellular fascicles of mildly to
moderately atypical spindle cells displaying an infiltrative pattern reminiscent
of lipofibromatosis or dermatofibrosarcoma protuberans. Immunohistochemically,
all cases co-expressed S100 protein and CD34. FISH analysis revealed NTRK1 gene
rearrangement in four of five cases tested. Clinical follow-up showed local
recurrence in three cases but no evidence of metastasis. This study further
supports that LPF-NT represents a novel entity of NTRK1-associated neoplasms.
Awareness of its clinicopathological features, immunophenotypes and cytogenetic
abnormalities helps pathologists arrive at the correct diagnosis.
PMID- 29958732
TI - Craniomaxillofacial patient-specific CAD/CAM implants based on cone-beam
tomography data - A feasibility study.
AB - Customized implants have simplified surgical procedures and have improved patient
outcome in craniomaxillofacial surgery. Traditionally, patient-specific data is
gathered by conventional computed tomography (CT). However, cone-beam CT (CBCT)
can generate a 3D reconstruction of the area of interest with a lower dose of
radiation at reduced cost. In this study, we investigated the feasibility of
using CBCT data to design and generate customized implants for patients requiring
craniomaxillofacial reconstruction. We used CBCT to generate 62 implants for 51
consecutive patients admitted to our department between January 2015 and December
2017. The indications for reconstruction and types of reconstruction were very
variable. In all cases, the implants were well fitted and no implant-related
complications were detected. Pre-surgical planning was faster and more efficient
as we did not have to consult a radiologist. Although CBCT data is more difficult
to process than conventional CT data for the implant provider, the clinical
advantages are pronounced and we now use CBCT as standard in our department. In
conclusion, we have shown that using CBCT to design and manufacture customized
implants for reconstruction of the craniomaxillofacial area is feasible and
recommend this approach to other departments.
PMID- 29958733
TI - Development and applications of the single-case design risk of bias tool for
evaluating single-case design research study reports.
AB - Systematic reviews and meta-analyses can be a useful method for synthesizing
evidence across multiple studies to draw conclusions about a research base. An
important aspect of rigorous systematic reviews is an assessment of the study
methods and potential biases impacting results or interpretations and conclusions
of the primary studies. Single-case design (SCD) research has been a primary
mechanism for identifying evidence-based practices across disciplines, but
primarily in behavioral fields and special education. While the Cochrane Risk of
Bias tool has been adapted for use in reviews of non-randomized studies, there is
currently no guidance for evaluating SCD research. Hence, we developed a single
case design risk of bias tool (SCD RoB) based on current conceptualizations of
biases that might affect the validity of claims from single-case design research.
We used the Cochrane risk of bias criteria and contemporary single-case design
quality indicators and design standards to guide development. We describe the SCD
RoB tool and two early applications of its use to demonstrate its application and
provide initial validation. We also provide an overview of future areas of
research using the SCD RoB tool in an effort to advance the science of single
case design research methods.
PMID- 29958734
TI - Days alive and free as an alternative to a mortality outcome in pivotal
vasopressor and septic shock trials.
AB - PURPOSE: RCTs in septic shock negative for mortality may show organ dysfunction
benefits. We hypothesized that RCTs in septic shock show significant differences
between treatment groups in organ support despite no mortality differences.
METHODS: RCTs of epinephrine vs. norepinephrine plus dobutamine, norepinephrine
vs. dopamine and vasopressin vs. norepinephrine reported days alive and free
("DAF") of vasopressors, ventilation and RRT, by subtracting days with support
from the lesser of 28 or days to death. We also assigned zero DAF to non
survivors ("DAF and Mortality") and calculated the composite "DAF vasopressors,
ventilation and RRT". RESULTS: Using "DAF", norepinephrine was better than
dopamine for vasopressors. In contrast, using "DAF and Mortality", norepinephrine
was better than dopamine for vasopressors, ventilation and RRT; norepinephrine +
dobutamine was better than epinephrine for ventilation. Using the novel composite
"DAF vasopressors, ventilation and RRT", norepinephrine + dobutamine was better
than epinephrine (p = 0.033), norepinephrine better than dopamine (p = 0.03), and
vasopressin better than norepinephrine in less severe shock (p = 0.03).
CONCLUSIONS: Differences between treatment groups in organ dysfunction in RCTs in
septic shock occur despite lack of mortality differences depending on calculation
method. If standardized and validated further, DAF could become the primary
endpoint of RCTs in septic shock.
PMID- 29958735
TI - Outcomes of Unstable Scaphoid Nonunion With Segmental Defect Treated With Plate
Fixation and Autogenous Cancellous Graft.
AB - PURPOSE: Treatment of scaphoid nonunion with a segmental defect presents a
challenging clinical problem. Various techniques have been proposed, often
involving structural grafting with vascularized and nonvascularized bone. The
authors hypothesize that satisfactory clinical and radiographic outcomes are
possible with a relatively simplified technique of volar plate fixation with
autogenous, purely cancellous graft. METHODS: The authors performed a
retrospective review of 34 patients with scaphoid nonunions with segmental
defects, treated with plate fixation and purely cancellous bone grafting. Cases
with avascular necrosis were excluded. Surgical management included a volar
incision, reduction, bone grafting from the ipsilateral distal radius and/or
olecranon, and application of a volar locking plate. Postoperative outcome
measures included time to union based on computed tomography, return to work and
sports, patient-reported pain and disability scores, grip strength, and range of
motion. RESULTS: Thirty-four patients with an average age of 31 years (range, 16
55 years) were treated with volar plate fixation and cancellous grafting, an
average of 34 months after initial injury. Twenty-six patients (76%) were treated
for nonunion at the scaphoid waist, 7 (21%) at the proximal pole, and 1 (3%) at
the distal pole. Mean final follow-up was 18.7 months (range, 12-34 months). When
union was defined by computed tomography evidence of healing, 2 (6%) scaphoids
healed by 6 weeks after surgery, 28 (82%) healed by 12 weeks, and 100% healed by
18 weeks. Mean Disabilities of the Arm, Shoulder, and Hand score improved from
27.1 +/- 7.3 before surgery to 11.8 +/- 5.8 after surgery. Grip strength,
corrected for hand dominance, improved from 77.5% of the nonsurgical side before
surgery to 90.5% after surgery. All employed patients returned to work, although
3 (9%) did not return to full capacity. CONCLUSIONS: The combination of scaphoid
plate fixation and pure cancellous bone grafting for scaphoid nonunion with
segmental defects yields reliable union rates and good patient outcomes.
Autogenous cancellous grafting may be an alternative to more technically
demanding or morbid grafting procedures for the treatment of scaphoid nonunion.
TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 29958736
TI - Impact of an electronic medical record reminder on hepatitis B vaccine initiation
and completion rates among insured adults with diabetes mellitus.
AB - OBJECTIVE: The Advisory Committee on Immunization Practices recommends Hepatitis
B (HepB) vaccine for previously unvaccinated adults <60 years with diabetes
mellitus. This observational retrospective cohort study assessed the impact of
implementing electronic provider reminders on HepB vaccine initiation and 3-dose
series completion rates among insured adults with diabetes aged 19-59 years old.
RESEARCH DESIGN AND METHODS: Difference-in-difference (DID) analyses compared
changes in vaccine initiation and completion rates (ratio of the rate ratio [RRR]
and 95% confidence interval [CI]) during 12 months pre- and post-implementation
between intervention and control sites. We examined trends in vaccine initiation
and completion rates by plotting monthly rates during the study period. We also
calculated the overall HepB vaccine coverage rates with 95% CI among all adults
with diabetes aged 19-59 years old at the start and end date of the study period.
RESULTS: Baseline HepB vaccine initiation and completion rates were similar at
both the intervention and control sites. Gender, age, and race/ethnicity
distributions within both sites were similar during the 12 months pre- and post
implementation. DID analyses demonstrated statistically significant differences
in the changes of the annual vaccine initiation rates (RRR: 70.7, 95% CI: 62.8
79.6) and the third dose completion rates (RRR = 18.7, 95% CI: 14.2-24.8) between
the two sites. The coverage increased significantly at the intervention site
while it remained low at the control site. CONCLUSIONS: Use of provider reminders
is highly effective in increasing both HepB vaccine initiation and series
completion rates among adults with diabetes.
PMID- 29958738
TI - Threats to oral polio vaccine acceptance in Somalia: Polling in an outbreak.
AB - BACKGROUND: Using a survey conducted during the 2013-2014 polio outbreak in
Somalia, this study examines attitudinal and knowledge-based threats to oral
polio vaccine acceptance and commitment. Findings address a key gap, as most
prior research focuses on endemic settings. METHODS: Between November 19 and
December 21, 2013, we conducted interviews among 2003 caregivers of children
under 5 years in select districts at high risk for polio transmission. Within
each district, sample was drawn via a multi-stage cluster design with random
route household selection. We calculated the percentage of caregivers who could
not confirm recent vaccination and those uncommitted to future vaccination. We
compared these percentages among caregivers with varying knowledge and attitudes,
focusing on variables identified as threats in endemic settings, using controlled
and uncontrolled comparisons. We also examined absolute levels of threat
variables. RESULTS: Only 10% of caregivers could not confirm recent vaccination,
but 32% were uncommitted to future vaccination. Being unvaccinated or uncommitted
were related to multiple threat variables. For example, compared with relevant
counterparts, caregivers were more likely to be unconfirmed and uncommitted if
they did not trust vaccinators "a great deal" (unconfirmed: 9% vs. 2%;
uncommitted: 49% vs. 28%), which is also true in endemic settings. Unlike endemic
settings, symptom knowledge was related to commitment while rumor awareness was
low and unrelated to past acceptance or commitment. Levels of trust and
perceptions of OPV effectiveness were high, though perceptions of community
support and awareness of logistics were lower. CONCLUSIONS: As in endemic
settings, outbreak responses will benefit from communications strategies focused
on enhancing trust in vaccinators, institutions and the vaccine, alongside making
community support visible. Disease facts may help motivate acceptance, and
enhanced logistics information may help facilitate caregiver availability at the
door. Quelling rumors early may be important to prevent them from becoming
threats.
PMID- 29958737
TI - Longevity of duodenal and peripheral T-cell and humoral responses to live
attenuated Salmonella Typhi strain Ty21a.
AB - BACKGROUND: We have previously demonstrated that polyfunctional Ty21a-responsive
CD4+ and CD8+ T cells are generated at the duodenal mucosa 18 days following
vaccination with live-attenuated S. Typhi (Ty21a). The longevity of cellular
responses has been assessed in peripheral blood, but persistence of duodenal
responses is unknown. METHODS: We vaccinated eight healthy adults with Ty21a.
Peripheral blood and duodenal samples were acquired after a median of 1.5 years
(ranging from 1.1 to 3.7 years) following vaccination. Cellular responses were
assessed in peripheral blood and at the duodenal mucosa by flow cytometry. Levels
of IgG and IgA were also assessed in peripheral blood by enzyme-linked
immunosorbent assay. RESULTS: No T-cell responses were observed at the duodenal
mucosa, but CD4+ T-cell responses to Ty21a and FliC were observed in peripheral
blood. Peripheral anti-lipopolysaccharide IgG and IgA responses were also
observed. Early immunoglobulin responses were not associated with the persistence
of long-term cellular immune responses. CONCLUSIONS: Early T-cell responses which
we have previously observed at the duodenal mucosa 18 days following oral
vaccination with Ty21a could not be detected at a median of 1.5 years. Peripheral
responses were observed at this time. Immunoglobulin responses observed shortly
after vaccination were not associated with cellular immune responses at 1.5
years, suggesting that the persistence of cellular immunity is not associated
with the strength of the initial humoral response to vaccination.
PMID- 29958739
TI - Potential cost-effectiveness of adjuvanted herpes zoster subunit vaccine for
older adults in Hong Kong.
AB - BACKGROUND: Adjuvanted herpes zoster (HZ) subunit vaccine is recommended for
adults aged >=50 years. This study aimed to investigate cost-effectiveness of HZ
subunit vaccine for older adults at different age in Hong Kong. METHODS: A life
long Markov model was designed to simulate outcomes of four alternatives:
Vaccination at model entry (age 50 years); deferring vaccination to 60 years;
deferring vaccination to 70 years; and no vaccination. Outcome measures included
direct cost, indirect cost, HZ and post-herpetic neuralgia incidences, quality
adjusted life years (QALYs) loss, and incremental cost per QALY saved (ICER).
Model clinical inputs were derived from literature. HZ treatment costs were
collected from a cohort of HZ patients (n = 218). One-way and probabilistic
sensitivity analyses were performed. RESULTS: In base-case analysis, vaccination
at 50 years showed highest QALYs saved and increment cost (0.00258; USD166),
followed by deferring to 60 years (0.00215 QALYs saved; USD102) and deferring to
70 years (0.00134 QALYs; USD62) when comparing to no vaccination. ICERs of
vaccination arms versus no vaccine (46,267-64,341 USD/QALY) were between 1-3 *
gross domestic product (GPD) per capita in Hong Kong (USD43,530-USD130,590). One
way sensitivity analyses found vaccine cost to be the common and most influential
parameter for ICER of each vaccination strategy to become <1 * GDP per capita. In
probabilistic sensitivity analysis, vaccination at 50 years, deferring to 60
years and 70 years were accepted as cost-effective in 90% of time at willingness
to-pay (WTP) of 78,400 USD/QALY, 57,680 USD/QALY and 53,760 USD/QALY,
respectively. CONCLUSIONS: Cost-effectiveness of each strategy is highly subject
to the vaccine cost and WTP threshold per QALY saved.
PMID- 29958740
TI - The value of endoplasmic reticulum stress markers (GRP78 and CHOP) in the
diagnosis of acute mesenteric ischemia.
AB - AIM: To evaluate levels of the endoplasmic reticulum (ER) stress markers GRP78
and CHOP in acute mesenteric ischemia (AMI) and to examine relations with degrees
of AMI-related intestinal injury. MATERIALS AND METHODS: Twenty-four rats were
divided into four groups. Group I and Group III represented the control groups,
from which blood and tissue specimens were collected 2 and 6 h after laparotomy
without superior mesenteric artery (SMA) ligation. Group II and Group IV
constituted the ischemia groups, from which blood and tissue specimens were
collected 2 and 6 h after SMA ligation. The ER stress markers GRP78 and CHOP,
total oxidant status (TOS), total antioxidant status (TAS), and the oxidative
stress index (OSI) were investigated in each group. Ileum specimens were assessed
in terms of ischemic injury, and appropriate comparisons were performed. RESULTS:
Significantly higher GRP78, CHOP, TOS, and TAS values were determined in the
ischemia groups (groups II and IV) compared to the control groups (groups I and
III). This elevation was greater in the 6 h ischemia group, the group exposed to
the greatest ischemic injury (Group IV). Significant and powerful correlation was
present between histopathological damage and levels of the ER stress markers and
oxidative markers. CONCLUSION: According to our results, ER stress markers (GRP78
and CHOP) increase significantly following ischemic injury. This elevation has
the potential to be used diagnostically and also in prognostic terms due to the
powerful correlation it exhibits with AMI-related ischemic injury.
PMID- 29958741
TI - Airway management in a prehospital combat setting.
PMID- 29958742
TI - Patient factors associated with nationwide emergency department utilization for
cellulitis.
PMID- 29958743
TI - Factor Xa inhibition and sPESI failure in intermediate-high-risk pulmonary
embolism.
AB - We report the case of a 61-year-old man who presented at the Emergency Department
(ED), complaining of sudden-onset dyspnea and chest pain after a long flight from
Tokyo to Houston. Considering his clinical stability and sPESI 0, enoxaparin 1
mg/kg BID was started for 24 h, and the patient was then considered for early
discharge with apixaban 10 mg BID. Direct-factor Xa inhibition did not improve
extensive thrombus burden and right ventricular dysfunction despite D-dimer
measurement reduction. Because of the treatment failure, we considered
thrombolysis. Currently, recommendations to use thrombolysis in patients under
non-vitamin K antagonist oral anticoagulants (NOACs) do not exist. Hence, the one
dose of apixaban was stopped, and 12 h later, we performed successful
thrombolysis. A systematic review from 2007 to 2017 did not identify any cases
related to NOACs failure to reduce thrombus burdens in patients with PE and
persistent right ventricular dysfunction. We also did not find any evidence of
cases that reported strategies for urgent thrombolysis in PE patients on NOACs.
To the best of our knowledge, apixaban's failure to reduce thrombus burden,
persistent right ventricular dysfunction, and a NOACs-thrombolysis bridge in
patients with PE on apixaban has not been previously described. Both the bedside
risk stratification and the therapeutic failures should alert clinicians in the
ED to the potential limitations of low-molecular-weight heparin, NOACs therapy,
and sPESI in the setting of intermediate-high-risk PE.
PMID- 29958744
TI - Impact of prehospital airway management on combat mortality.
PMID- 29958745
TI - Preclinical assessment of safety and efficacy of intravenous delivery of
autologous adipose-derived regenerative cells (ADRCs) in the treatment of severe
thermal burns using a porcine model.
AB - OBJECTIVE: A number of studies have reported that application of autologous
adipose-derived cell populations leads to improved outcome in different
preclinical models of thermal burn injury. However, these studies were limited to
assessment of relatively small injuries amounting to only ~2% of total body
surface area (TBSA) in which the complications associated with large burns (e.g.:
systemic inflammation and the need for fluid resuscitation) are absent. In
anticipation of translating this approach to a clinical trial in which these
complications would be present we applied a preclinical model that more closely
resembles a patient with large thermal burn injury requiring skin grafting. Thus,
the present study used a porcine model to investigate safety and efficacy of
intravenous delivery of ADRCs in the treatment of a complex burn injury
comprising ~20% TBSA and including both moderately deep (44%) partial and full
thickness burns, and the injury associated with skin graft harvest. METHODS: Two
pairs of full thickness and partial thickness burns involving in total ~20% TBSA
were created on the back of Yorkshire pigs (n=15). Three days post-burn, full
thickness wounds were excised and grafted with a 3:1 meshed autologous split
thickness skin graft (STSG). Partial thickness wounds were not treated other than
with dressings. Animals were then randomized to receive intravenous delivery of
ADRCs (n=8) or vehicle control (n=7). Safety was assessed by monitoring systemic
parameters (blood gases, hematology, and clinical chemistry) throughout the
course of the study. Wound healing for both types of burn wound and for the skin
graft donor sites was followed for 18days using wound imaging, histology, and
trans-epidermal water loss (TEWL; skin barrier function assessment). RESULTS: No
serious adverse events related to ADRC infusion were noted in any of the animals.
Delivery of ADRCs appeared to be safe with none of the systemic safety parameters
worsened compared to the control group. TEWL and histological analyses revealed
that ADRC treatment was associated with significantly accelerated healing of skin
graft (27.1% vs. 1.1% on Day 5 post-grafting), donor site (52.8% vs. 33.1% on Day
5 post-excision) and partial thickness burn (81.8% vs. 59.8% on Day 18 post
treatment). Data also suggested that ADRC treatment improved parameters
associated with skin graft elasticity. CONCLUSIONS: This study demonstrated that
intravenous delivery of autologous ADRCs appears to be a safe and feasible
approach to the treatment of large burns and supports the use of ADRCs as an
adjunct therapy to skin grafting in patients with severe burns.
PMID- 29958746
TI - Assessment of quality-of-life in patients with face-and-neck burns: The Burn
Specific Health Scale for Face and Neck (BSHS-FN).
AB - INTRODUCTION: Burns to the cephalic extremities are particularly implicated in
problems of self-image and alterations to personal social relations. The aim of
this study was to objectively assess the quality-of-life (QoL) of patients
suffering from face-and-neck burns through our newly created scale: The Burn
Specific Health Scale for Face and Neck (BSHS-FN). METHODS: After constructing
the BSHS-FN, we compared QoL of patients with or without face-and-neck burns. SF
36, the French version of the BSHS-B (Burn Specific Health Scale-Brief), and the
BSHS-FN were administrated to 53 patients divided into two groups: GB group
(general burns, 26 patients) and FN group (face-neck burns, 27 patients).
RESULTS: QoL evaluated using the SF-36 had a higher average total score in GB
patients compared to FN patients, but there were no significant difference
between the two groups (54.3+/-18.5 vs. 47.0+/-17.3, respectively, p=0.11). In
contrast, in BSHS-B the total score was significantly different between the two
groups with a higher score recorded for the GB group (71.9+/-13.4 [median: 72.8]
in the GB group vs. 62.2+/-14.4 [median: 64.4] in the FN group). In percentage
terms, total score of BSHS-FN for GB group was 79.1+/-10.1, while total score for
FN group was 53.6+/-13.1 (p<0.001), with the highest score for the Face and Neck
domain in GB group (99.7+/-1.1, p<0.001) CONCLUSION: The BSHS-FN seemed to be
more appropriate to assess QoL for FN burn patients. This study supports its
application in routine clinical practice and in international studies.
PMID- 29958747
TI - Added value of the DIC score and of D-dimer to predict outcome after successfully
resuscitated out-of-hospital cardiac arrest.
AB - BACKGROUND: Recent Korean data suggest a high prevalence of overt disseminated
intravascular coagulation (DIC) and a good predictive performance of the ISTH DIC
score in successfully resuscitated out-of-hospital cardiac arrest. OBJECTIVES: We
hypothesised that in a European cohort of resuscitated out-of-hospital cardiac
arrest patients the prevalence of DIC is substantially lower. Furthermore, the
determination of D-dimer levels at admission, but not the DIC score, could
improve mortality prediction above traditional predictors. PATIENTS/METHODS: Data
were extracted from a prospective cardiac arrest registry including patients
admitted between 2006 and 2015, who achieved return of spontaneous circulation
and had parameters for DIC score calculation available. The primary outcome was
the prevalence of overt DIC at admission. Secondary outcomes included the
association of overt DIC with 30-day mortality and the contribution of the DIC
score and D-dimer levels to 30-day mortality prediction using logistic
regression. Three stepwise models were evaluated by receiver-operating
characteristic analysis. RESULTS: Out of 1179 patients 388 were included in the
study. Overt DIC was present in 8% of patients and associated with substantial 30
day mortality (83% vs. 39%). The AUC for model 1, including traditional mortality
predictors, was 0.83. The inclusion of D-dimer levels significantly improved
prognostication above traditional predictors (model 3, AUC 0.89), whereas the
inclusion of the DIC Score had no effect on mortality prediction (model 2, AUC
0.83). CONCLUSION: Overt DIC was rare in a European cohort of out-of-hospital
cardiac arrest patients. D-dimer levels improved 30-day mortality prediction and
provided added value to assess early mortality risk after successful
resuscitation.
PMID- 29958748
TI - Association between reduced renal function and cardiovascular mortality in
patients hospitalized with infection: A multi-center cohort study.
AB - BACKGROUND: Infection is one of the main reasons for hospitalization worldwide,
and is associated with an increased risk of cardiovascular mortality. It is
unclear whether this association is modified by the presence of reduced renal
function. The aim of this study was to analyze the relationship between estimated
glomerular filtration rate (eGFR) and cardiovascular mortality in patients
hospitalized with infection. METHODS: This cohort study included all adult,
incident patients who were hospitalized at one of four hospitals in China between
2012 and 2015, had a discharge diagnosis of infection, and had a serum creatinine
measurement at admission. Patients receiving renal replacement therapy were
excluded. Hospital data were linked to death registry data. All-cause and
cardiovascular mortality were evaluated according to admission eGFR [>=60
(reference), 30-59 and < 30 mL/min/1.73m2] using multivariable Cox regression and
competing risk analyses. RESULTS: During a median follow-up period of 2.39 years,
40,524 patients were hospitalized with infection (mean age 61 years, 54.3% female
18.4% diabetic). Of these, 4781 died. Lower admission eGFR was associated with
progressively increased risks of cardiovascular mortality (>=60 mL/min/1.73m2
reference; 30-59 mL/min/1.73m2 subdistribution hazard ratio [SHR] 2.15, 95% CI
1.85-2.50, P< .01; <30 mL/min/1.73m2 SHR 3.19, 95% CI 2.68-3.80, P < .01). The
proportion of deaths due to cardiovascular disease increased as the eGFR
decreased, predominantly due to ischemic heart disease. CONCLUSIONS: Patients
hospitalized with infections and reduced renal function have significantly
increased risks of cardiovascular mortality. Heart status should be carefully
monitored following infections, especially for those with reduced renal function.
PMID- 29958749
TI - Cognitive therapies for psychosis: Advances and challenges.
PMID- 29958750
TI - Measuring theory of mind in schizophrenia research: Cross-cultural validation.
AB - Theory of mind (ToM) is the ability to understand mental states of others and it
is crucial for building sensitivity to other persons or events. Measuring ToM is
important for understanding and rehabilitating social cognitive impairments in
persons with schizophrenia. The Social Attribution Task-Multiple Choice (SAT-MC)
has been successfully employed to measure ToM between individuals with
schizophrenia (SZ) and healthy controls (HC) in North America. Given that the SAT
MC uses geometric shapes, is nonverbal and less culturally loaded than other
social cognition measures, it may serve for measuring ToM in schizophrenia across
cultures. A total of 120 participants (30 per group; Korean SZ; Korean HC; North
American SZ; North American HC) were selected from existing databases to examine
the reliability and validity of the SAT-MC. Internal consistency, factor
structure, measurement invariance, discriminant validity, and
convergent/divergent validity were examined. The SAT-MC had good internal
consistency regardless of the clinical and cultural group as evidence by
Cronbach's alpha >= 0.78 in all groups. Confirmatory factor analysis confirmed
the one-factor model with a good model fit (chi2 = 188.122, TLI = 0.958, CFI =
0.963, RMSEA = 0.045). The SAT-MC was sensitive to detect individual differences
in ToM of SZ and HC, regardless of culture (p < 0.001), and significantly
correlated with other social cognition tasks (Hinting and Reading the Mind in the
Eyes Test) among Korean and North American patients. The SAT-MC is a reliable
measure for evaluating ToM in both Koreans and North Americans with or without
schizophrenia, supporting its potential utility in diverse language and cultures
for schizophrenia research.
PMID- 29958752
TI - Letter to the editors: Reducing stigmatizing attitudes in high school adolescents
- a cluster RCT on the effectiveness of a schizophrenia documentary.
PMID- 29958751
TI - Adolescent inhalant use and psychosis risk - a prospective longitudinal study.
AB - BACKGROUND: Cross-sectional studies have suggested inhalant use is associated
with psychosis. This association was examined in a longitudinal study accounting
for other substance use and potential confounders. METHODS: We used a prospective
sample (N = 6542) from the Northern Finland Birth Cohort 1986. Self-report
questionnaires on substance use and psychotic experiences were completed when the
cohort members were 15-16 years old. Inhalant use was categorized into four
groups (never, once, 2-4 times, 5 times or more). Subsequent psychosis diagnoses
(ICD-10) until age 30 years were obtained from national registers. Cox regression
analysis was used to examine the association between adolescent inhalant use and
risk of psychosis. RESULTS: During the observation period 124 individuals were
diagnosed with incident psychosis. Overall, there were 225 (3.4%) subjects with
any inhalant use, 18 (8.0%) of whom were diagnosed with psychosis during the
follow up. Of non-inhalant users (n = 6317) 106 (1.7%) were diagnosed with
psychosis. Compared to non-users, those using inhalants had increased risk of
incident psychosis with most frequent inhalant use associated with the greatest
risk (unadjusted HR = 9.46; 3.86-23.20). After adjusting for baseline psychotic
experiences, other substance use, comorbid mental disorder and parental substance
abuse, the increased risk of psychosis persisted (HR = 3.06; 1.05-8.95).
Furthermore, a dose-response effect between inhalant use and risk of psychosis
was identified (OR = 2.34; 1.83-2.99). CONCLUSIONS: Inhalant use in adolescence
was independently associated with incident psychosis. The adverse health outcomes
associated with adolescent inhalant use provide compelling reasons for
implementation of policies to reduce the use of volatile substances in
adolescents.
PMID- 29958753
TI - Variation in Use of Postoperative Precautions and Equipment Following Total Hip
Arthroplasty: A Survey of the AAHKS and CAS Membership.
AB - BACKGROUND: A traditional method to reduce dislocation risk following total hip
arthroplasty involves prescribing postoperative precautions and ambulatory
equipment to patients. The purpose of this study was to determine the prevalence
of postoperative precaution and equipment use among North American arthroplasty
surgeons for patients undergoing primary total hip arthroplasty. METHODS: We
conducted a survey of American Association of Hip and Knee Surgeons and Canadian
Arthroplasty Society members using an electronic questionnaire format to
determine how often precautions and equipment were prescribed, and whether their
use was associated with surgical approach and other surgeon demographics.
RESULTS: Of the respondents, 44% universally prescribed precautions while 33%
never prescribed precautions. Use of the posterolateral approach, surgeon
experience, and larger head size use were significantly associated (P < .01) with
precaution and equipment use. Direct anterior approach surgeons were
significantly less likely to prescribe precautions (P < .0001) and significantly
less likely to prescribe equipment (P < .0001). CONCLUSION: Although
postoperative precautions continue to be used to some degree by the majority of
members, their consumption of healthcare resources through utilization of
additional care providers and purchasing of equipment, known association with
reduced patient satisfaction, and lack of supporting evidence make them a target
for future scrutiny.
PMID- 29958754
TI - Preoperative Opioid Use and Its Association With Early Revision of Total Knee
Arthroplasty.
AB - BACKGROUND: Few studies have evaluated the impact of preoperative opioid use on
risk of subsequent revision following primary total knee arthroplasty (TKA). The
purpose of this study was to determine whether preoperative opioid use is
associated with an increased risk of early revision TKA. METHODS: The Humana
administrative claims database was queried to identify patients who underwent
unilateral TKA during the years 2007-2015. Patients were tracked for the
occurrence of an ipsilateral revision procedure within 2 years. Preoperative
opioid use was defined as having an opioid prescription filled within the 3
months before TKA. Age, sex, diabetes, obesity, chronic kidney disease, and
anxiety/depression were also analyzed. Univariate and multivariate analyses were
performed. RESULTS: A total of 35,894 primary TKA patients were identified and
1.2% (n = 413) had a revision TKA procedure within 2 years. 29.2% of patients
filled an opioid prescription within the 3 months before TKA. Preoperative opioid
users were significantly more likely to undergo early TKA revision (1.6% vs 1.0%,
P < .001). Preoperative opioid use (odds ratio [OR], 1.53; 95% confidence
interval [CI], 1.25-1.88; P < .001), younger age (OR, 2.46; 95% CI, 1.43-3.95; P
< .001), obesity (OR, 1.25; 95% CI, 1.01-1.56; P = .04), and smoking (OR, 1.66;
95% CI, 1.22-2.22; P < .001) were associated with early revision TKA. CONCLUSION:
This study identified preoperative opioid use as being independently associated
with a greater risk for an early revision TKA. Younger age, obesity, and smoking
were also associated with elevated risk. These findings support efforts to reduce
inappropriate opioid prescribing.
PMID- 29958755
TI - Risk Factors Associated With Early Complications of Revision Surgery for Head
Neck Taper Corrosion in Metal-on-Polyethylene Total Hip Arthroplasty.
AB - BACKGROUND: Adverse local tissue reactions (ALTRs) due to tribocorrosion of head
neck taper junctions in contemporary metal-on-polyethylene (MoP) total hip
arthroplasty (THA) are emerging as an important reason for failure requiring
revision surgery. This study aimed at: (1) reporting early complication rates and
outcome, and (2) identifying risk factors associated with complications of
revision surgery for head-neck taper corrosion in patients with MoP THA. METHODS:
Forty consecutive revision surgeries in 39 patients (male, 16; female, 23) with
MoP THA were evaluated. The follow-up period after revision was a minimum of 14
months (range, 14-45). The indication for revision surgery was the presence of
symptomatic ALTR on magnetic resonance imaging (MRI) with elevated metal ion
levels. RESULTS: The overall complication rate was 25% and the reoperation rate
was 10%. The median serum level of cobalt ions decreased significantly 8.2 MUg/L
(1.2-56.1 MUg/L) pre-revision to 3.1 MUg/L (0.2-14.0 MUg/L) post-revision (P <
.01). High fretting and corrosion grades (Goldberg score >= 3) were observed in
82% of retrieved implants. MRI findings of solid lesion(s) with abductor
deficiency (P < .01) and intraoperative tissue damage at revision (P = .02) were
significantly associated with post-revision complications. CONCLUSION: A high
rate of early complications (25%) and re-revisions (10%) was observed after
revision of ALTR associated with head-neck taper corrosion. Pre-revision MRI
findings of solid lesion(s) with abductor deficiency and intraoperative tissue
damage were risk factors associated with the occurrence of a complication after
revision surgery. This information provides clinically useful information for
clinical decision-making and preoperative counseling of MoP THA patients
undergoing revision surgery for head-neck taper corrosion.
PMID- 29958756
TI - Reduction of ipsilateral thalamic volume in temporal lobe epilepsy with
hippocampal sclerosis.
AB - The thalamus plays an important role in the modulation of both focal and
generalized seizures, but the mechanisms related to seizures may be different
among epilepsy syndromes. The aim of this study is to investigate the thalamic
atrophy in different epilepsy syndromes. We enrolled a total of 72 patients with
epilepsy (22 patients with temporal lobe epilepsy with hippocampal sclerosis, 21
patients with extra-temporal lobe epilepsy, and 29 patients with juvenile
myoclonic epilepsy). We analyzed structural volumes of the brain with FreeSurfer
5.1 software, and compared them among subgroups of epilepsy and normal control
subjects. Moreover, we quantified correlations between the duration of epilepsy
and the structural volumes with age and sex as covariates. The volumes of the
ipsilateral hippocampus in temporal lobe epilepsy with hippocampal sclerosis were
significantly smaller than those in extra-temporal lobe epilepsy and normal
control subjects [analysis of variance (ANOVA), p < 0.001]. Although the volumes
of the ipsilateral thalamus were not different from those of normal control
subjects, the volumes of the ipsilateral thalamus were negatively correlated with
duration of epilepsy in temporal lobe epilepsy with hippocampal sclerosis (r =
0.5, p = 0.02). However, the volumes of interest in extra-temporal lobe epilepsy
and juvenile myoclonic epilepsy were not different from those in normal control
subjects, and none of these structures were correlated with duration of epilepsy.
These findings suggest that the role of the thalamus may be different in thalamo
limbic circuits among epilepsy syndromes.
PMID- 29958757
TI - Meningioma in the elderly: Characteristics, prognostic factors, and surgical
strategy.
AB - Meningioma is one of the most common intracranial tumors. It has the features of
benign and slow growing. We focused on the meningioma in the elderly,
retrospectively analyzed 528 valid meningioma patients, including 115 (21.8%)
patients older than 65 years old. The elderly patients were shown to have
significantly larger tumor diameter (mean [+/-SD] 43.4 +/- 18.0 mm) comparing
with the young group (mean [+/-SD] 37.6 +/- 16.5 mm, p < 0.01). Post-operative
KPS was significantly lower in the elderly group (mean [+/-SD] 79.64 +/- 26.37)
than the young group (mean [+/-SD] 88.81 +/- 17.36, p < 0.01). Multivariate
regression of post-operative KPS scales at discharge and 6 months follow-up
showed operative complications, pre-operative comorbidities, tumor diameter, and
challenging location had a significant impact on the outcome. However, tumor
blood supply, Simpson grades, pathology, and pre-operative symptoms were shown to
have less impact on the post-operative KPS scale. The outcome for meningioma in
elderly patients was affected by factors related more to the safety of the
operation than characteristics of the tumor. Therefore, rather than achieving
total resection, conservative and safety preferential treatment strategies should
be regarded as a higher priority for better quality of life.
PMID- 29958758
TI - The use of dietary supplements and perceived quality of life in patients with
Parkinson's disease.
AB - Patients with chronic illnesses represent a segment of adults among whom intake
of dietary supplements is particularly prevalent. Previous studies have shown
that intake of different dietary supplements to improve perceived quality of life
of patients with or without objective improvement in other physiological
parameters. We recently conducted an open-label trial of blackcurrant anthocyanin
supplementation in patients with PD. Participants were administered the PDQ-39 (a
39-item quality-of-life instrument) before and after blackcurrant
supplementation. Patients scored significantly lower in the emotional well-being
domain (i.e., reported better emotional quality of life) after blackcurrant
anthocyanin supplementation (t9 = -3.97, p = 0.008). It is plausible that the
attention our participants received during the study period could have positively
affected their mood. It is also possible that a placebo effect of the fruit
derived supplement-often viewed as a healthy alternative to medicines-was in
play. Our findings reiterate the high prevalence of supplement intake among PD
patients, and the importance of being attentive when caring for patients whether
they take supplements or not.
PMID- 29958759
TI - Three-Dimensional Echocardiographic Guidance of Right Heart Catheterization
Decreases Radiation Exposure in Atrial Septal Defect Closures.
AB - BACKGROUND: Radiation reduction is desirable in children undergoing cardiac
catheterization. Three-dimensional (3D) transesophageal echocardiographic (3D
TEE) imaging obviates the need for mental reconstruction of 3D structures from
two-dimensional images. Three-dimensional TEE imaging is used in atrial septal
defect (ASD) closures. Three-dimensional TEE guidance of right heart
catheterization (RHC) without fluoroscopy for ASD closures has not been
demonstrated. The aim of this study was to evaluate the feasibility of 3D TEE
guidance of RHC in ASD closures and radiation reduction compared with historical
control subjects. METHODS: Twenty-two patients underwent 3D TEE guidance of RHC
and ASD closures and were compared with 44 control subjects. RHC time, total
fluoroscopy time, radiation dose, and procedural time were compared. Fluoroscopy
time during RHC was recorded in patients undergoing 3D TEE guidance. RESULTS:
There was a 54% reduction in total fluoroscopy time and a 78% radiation reduction
demonstrated with 3D TEE guidance of patients with ASDs compared with control
subjects. Although there were no statistically significant differences in the RHC
time compared with control subjects, the fluoroscopy time (mean, 0.06 +/- 0.23
min) for RHC guidance using 3D TEE imaging was almost zero. There was decreased
RHC time as we progressed through the learning curve of performing 3D TEE
guidance of RHC (r = -0.63, P < .01). There were no statistically significant
differences in total procedural time. CONCLUSIONS: Three-dimensional TEE guidance
in RHC is feasible without the use of fluoroscopy and reduces radiation exposure
in percutaneous ASD closures. Three-dimensional TEE guidance may be used in other
interventional procedures in the future to further reduce radiation exposure and
facilitate catheter interventions.
PMID- 29958760
TI - Three-Dimensional Echocardiography for the Assessment of Right Ventriculo
Arterial Coupling.
AB - BACKGROUND: The analysis of right ventriculo-arterial coupling (RVAC) from
pressure-volume loops is not routinely performed. RVAC may be approached by the
combination of right heart catheterization (RHC) pressure data and cardiac
magnetic resonance (CMR)-derived right ventricular (RV) volumetric data. RV
pressure and volume measurements by Doppler and three-dimensional
echocardiography (3DE) allows another way to approach RVAC. METHODS: Ninety
patients suspected of having pulmonary hypertension underwent RHC, 3DE, and CMR
(RHC mean pulmonary artery pressure [mPAP] 37.9 +/- 11.3 mm Hg; range, 15-66 mm
Hg). Three-dimensional (3D) echocardiography was performed in 30 normal patients
(echocardiographic mPAP 18.4 +/- 3.1 mm Hg). Pulmonary artery (PA) effective
elastance (Ea), RV maximal end-systolic elastance (Emax), and RVAC (PA Ea/RV
Emax) were calculated from RHC combined with CMR and from 3DE using simplified
formulas including mPAP, stroke volume, and end-systolic volume. RESULTS: Three
dimensional echocardiographic and RHC-CMR measures for PA Ea (3DE, 1.27 +/- 0.94;
RHC-CMR, 0.71 +/- 0.52; r = 0.806, P < .001), RV Emax (3DE, 0.72 +/- 0.37; RHC
CMR, 0.38 +/- 0.19; r = 0.798, P < .001), and RVAC (3DE, 2.01 +/- 1.28; RHC-CMR,
2.32 +/- 1.77; r = 0.826, P < .001) were well correlated despite a systematic
overestimation of 3DE elastance parameters. Among the whole population, 3D
echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D
echocardiographic RV Emax were significantly lower in patients with mPAP < 25 mm
Hg (n = 41) than in others (n = 79). Among the 90 patients who underwent RHC, 3D
echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D
echocardiographic RV Emax increased significantly with increasing levels of
pulmonary vascular resistance. CONCLUSIONS: Three-dimensional echocardiography
derived PA Ea, RV Emax, and RVAC correlated well with the reference RHC-CMR
measurements. Ea and RVAC but not Emax were significantly different between
patients with different levels of afterload, suggesting failure of the right
ventricle to maintain coupling in severe pulmonary hypertension.
PMID- 29958761
TI - Which Cardiac Structure Lies Nearby? Revisiting Two-Dimensional Cross-Sectional
Anatomy.
AB - Two-dimensional (2D) transthoracic echocardiography is one of the most used
diagnostic tools in clinical cardiology. Similarly, 2D transesophageal
echocardiography is considered an indispensable tool for cardiologists and
cardiac anesthesiologists worldwide. However, because of their tomographic
nature, both techniques display only thin cut planes of a given area of the
heart, which are far from representing the "anatomic reality." It is widely
accepted that experienced echocardiographers are able to reconstruct mentally a
three-dimensional image of any cardiac structure on the basis of their
interpretation of multiple tomographic slices. However, this may not be the case
with less experienced echocardiographers. In particular, the authors noticed that
less experienced echocardiographers are almost totally unaware of which
structures lie "nearby" a given 2D tomographic plane, that is, what is adjacent
in the elevation plane. In this article, the authors report the use of three
dimensional transesophageal echocardiographic images to discover which structures
are located nearby (i.e., "behind" and "in front") the corresponding 2D cross
sections. The authors believe that this novel use of three-dimensional
echocardiography is a unique aid to disclose what cannot be seen in a given 2D
cross-section, thereby expanding our understanding of 2D echocardiographic
anatomy. This may be an effective method to encourage all to "think" in three
dimensions, even when they use 2D echocardiography.
PMID- 29958762
TI - Discovery and characterization of N-(1,3-dialkyl-1H-indazol-6-yl)-1H-pyrazolo[4,3
b]pyridin-3-amine scaffold as mGlu4 positive allosteric modulators that mitigate
CYP1A2 induction liability.
AB - Previous reports from our laboratory disclosed the structure and activity of a
novel 1H-pyrazolo[4,3-b]pyridine-3-amine scaffold (VU8506) which showed excellent
potency, selectivity and in vivo efficacy in preclinical rodent models of
Parkinson's disease. Unfortunately, this compound suffered from significant
CYP1A2 induction as measured through upstream AhR activation (125-fold) and thus
was precluded from further advancement in chronic studies. Herein, we report a
new scaffold developed recently which was systematically studied in order to
mitigate the CYP1A2 liabilities presented in the earlier scaffolds. We have
identified a novel structure that maintains the potency and selectivity of other
mGlu4 PAMs, leading to 9i (hmGlu4 EC50 = 43 nM; AhR activation = 2.3-fold).
PMID- 29958763
TI - Synthesis, antitumor activity evaluation and mechanistic study of novel
hederacolchiside A1 derivatives bearing an aryl triazole moiety.
AB - In an attempt to arrive at a more potent antitumor agent than the parent natural
saponin hederacolchiside A1, 23 hederacolchiside A1 derivatives (4a-4w) were
synthesized via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition and
screened in vitro for cytotoxicity against six human cancer cell lines. The
structure-activity relationship of these compounds was elucidated, and the
biological screening results showed that most of the compounds exhibited moderate
to high levels of antitumor activities against the tested cell lines and some of
them displayed more potent inhibitory activities compared with hederacolchiside
A1. Compound 4f showed a 2- to 7-fold more potent activity than hederacolchiside
A1. The mechanistic study of 4f revealed that this compound can induce cell
apoptosis in HepG2 cells via mitochondrial-mediated intrinsic pathways.
PMID- 29958764
TI - Iranian mothers' Experiences with Children Undergoing Hemodialysis: A Hermeneutic
Phenomenological Study.
AB - PURPOSE: To describe Iranian mothers' perspectives regarding hemodialysis for
their children. DESIGN AND METHODS: This qualitative study was conducted using
the hermeneutic phenomenological approach. The sample consisted of 11 mothers,
among whom five were interviewed once and six were interviewed twice, for a total
of 17 interviews. The data were then analyzed using van Manen's (1997) method.
RESULTS: Five themes emerged from the data: mothers enclosed by child care,
emotional and psychological tension, acceptance and contrivance, the entire
family being a victim of a sick child, and self-devotion. CONCLUSION: The results
indicated that the mothers of children undergoing hemodialysis experience
multiple stresses in the physical, emotional-psychological, social, and economic
dimensions. PRACTICAL IMPLICATIONS: Nurses are the healthcare team members who
most frequently interact with mothers of children undergoing hemodialysis. They
are therefore positioned favorably to provide the information and emotional
support needed by these mothers. Nurses are also among the frontline
professionals who can provide services designed to assess the physical,
psychological, and economic requirements of these mothers and their families.
PMID- 29958765
TI - Motivational interviewing training for medical students: A pilot pre-post
feasibility study.
AB - OBJECTIVE: To evaluate the impact of brief training in motivational interviewing
(MI) from a non-specialist professional for medical students. METHODS: Students
(n = 20) received three four-hour sessions of MI training over one week. They
interviewed caregivers acting as patients in two standardised medical situations,
six weeks before and three weeks after training. Global scores from the MITI
3.1.1 code, including "MI- Spirit", were attributed to the audiotaped interviews
by two independent coders, blind the pre- or post-training status of the
interview. Secondary outcomes were: caregivers' perception of students' empathy
(CARE questionnaire), students' evaluation of self-efficacy to engage in a
patient-centred relationship (SEPCQ score), and students' satisfaction with their
own performance (analogue scale). RESULTS: MI-Spirit score increased
significantly after training (p < 0.0001, effect size 1.5). Limited improvements
in CARE score (p = 0.034, effect size 0.5) and one of the SEPCQ dimensions
(sharing information and power with the patient; p = 0.047, effect size 0.5) were
also noted. Students' satisfaction score was unaffected (p = 0.69). CONCLUSION:
These findings suggest that brief MI training can improve communication skills in
medical students. PRACTICE IMPLICATIONS: Such an intervention is feasible and
could be generalised during medical studies.
PMID- 29958766
TI - Femtosecond laser-assisted cataract surgery in Fuchs endothelial corneal
dystrophy: Long-term outcomes.
AB - PURPOSE: To compare the corneal endothelial cell loss and central corneal
thickness (CCT) after conventional phacoemulsification surgery or femtosecond
laser-assisted cataract surgery in patients with Fuchs endothelial corneal
dystrophy and senile cataract. SETTING: Xiamen Ophthalmic Center, Affiliate
Xiamen University, Xiamen, China. DESIGN: Prospective case series. METHODS: Eyes
with mild or moderate Fuchs endothelial corneal dystrophy and cataracts had
femtosecond laser-assisted cataract surgery or phacoemulsification. The
endothelial cell density (ECD), rate of ECD loss, cumulative dissipated energy
(CDE), and CCT were measured preoperatively and 3 days and 1, 3, 6, and 12 months
postoperatively. RESULTS: The study evaluated 31 eyes. The CDE was lower in the
femtosecond group than in the phacoemulsification group (P < .05). The
preoperative and postoperative ECDs were similar in the 2 groups (P > .05). The
rate of ECD loss was higher in the phacoemulsification group from 1 to 12 months
postoperatively (P > .05). The CCT was thicker in the phacoemulsification group
1, 3, and 6 months postoperatively (all P > .05). In both groups, the
postoperative CCT at all follow-up visits were greater than the preoperative CCT
(all P < .01). No bullous keratopathy or other intraoperative complications
occurred in either group during the follow-up. CONCLUSIONS: For eyes with Fuchs
endothelial corneal dystrophy and cataract, the CCT 12 months after surgery
remained thicker than the preoperative thickness. The femtosecond group, with a
lower CDE, tended to have a thinner CCT and less endothelial cell loss than the
phacoemulsification group.
PMID- 29958767
TI - MEG revealed new functional hub of atypical brain network in autism spectrum
disorders.
PMID- 29958769
TI - Reinitiation of centrifugal ventricular assist device support after failed
attempt at cardiac recovery.
PMID- 29958768
TI - Refinement and Analysis of the Mature Zika Virus Cryo-EM Structure at 3.1 A
Resolution.
AB - Among the several arthropod-borne human flaviviral diseases, the recent outbreak
of Zika virus (ZIKV) has caused devastating birth defects and neurological
disorders, challenging the world with another major public health concern. We
report here the refined structure of the mature ZIKV at a resolution of 3.1 A as
determined by cryo-electron microscopic single-particle reconstruction. The
improvement in the resolution, compared with previous enveloped virus structures,
was the result of optimized virus preparation methods and data processing
techniques. The glycoprotein interactions and surface properties of ZIKV were
compared with other mosquito-borne flavivirus structures. The largest structural
differences and sequence variations occur at the glycosylation loop associated
with receptor binding. Probable drug binding pockets were identified on the viral
surface. These results also provide a structural basis for the design of vaccines
against ZIKV.
PMID- 29958770
TI - Escherichia coli chromosome-based T7-dependent constitutive overexpression system
and its application to generating a phenylalanine producing strain.
AB - Many metabolic engineering approaches have been attempted to generate strains
capable of producing valuable compounds. One of main goals is industrial
application of these strains. Integration of synthetic pathway genes into the
Escherichia coli chromosome enables generation of a plasmid-free strain that is
stable and useful for industrial applications. Strains that do not require
induction are advantageous in terms of cost. In the present study, we constructed
a constitutive overexpression system in E. coli to generate plasmid-free and
inducer-free strains. The T7 RNA polymerase/T7 promoter overexpression system,
which is an isopropyl-beta-d-thiogalactopyranoside (IPTG)-inducible gene
overexpression system (T7-dependent inducible overexpression system), was
modified to be a constitutive overexpression system. The constructed
overexpression system, a "chromosome-based T7-dependent constitutive
overexpression system", was applied in a metabolic engineering study to generate
a plasmid-free and inducer-free phenylalanine producing strain of E. coli.
PMID- 29958771
TI - Production of fucoxanthin, chrysolaminarin, and eicosapentaenoic acid by
Odontella aurita under different nitrogen supply regimes.
AB - Microalgae are recognized as promising producers of many bioactive products, but
their utility is limited due to high production costs. We subjected the marine
diatom Odontella aurita to three nitrogen supply regimes [initial low nitrogen
(ILN), initial high nitrogen (IHN), and initial high nitrogen plus supplementary
nitrogen (SN)] to investigate the accumulation of three high-value bioactive
components: fucoxanthin, chrysolaminarin and eicosapentaenoic acid (EPA). We
found that SN conditions maximized fucoxanthin accumulation: a maximum
productivity of 6.01 mg L-1 d-1 was obtained, a 4.32-fold and 1.42-fold increase
over production in the ILN and IHN groups, respectively. After nitrogen was
depleted in the growth medium, chrysolaminarin became the dominant energy storage
compound. Chrysolaminarin content rose to 60.33% of dry weight (DW) in the ILN
group, and 46.27% of DW in the IHN group. Variations in fatty acid composition
across the different nitrogen supply regimes indicated that EPA primarily
accumulated in the glycolipids, especially when nitrogen supply was sufficient.
The maximum productivity of chrysolaminarin (161.55 mg L-1 d-1) and EPA (9.37 mg
L-1 d-1) was observed in the IHN group. However, IHN conditions did not maximize
overall content of either compound. Our results demonstrated that O. aurita is
potentially useful as a producer of a variety of bioactive products; the
compounds produced by this species can be controlled by altering the nitrogen
supply.
PMID- 29958772
TI - Parotid gland fat related Magnetic Resonance image biomarkers improve prediction
of late radiation-induced xerostomia.
AB - PURPOSE: This study investigated whether Magnetic Resonance image biomarkers (MR
IBMs) were associated with xerostomia 12 months after radiotherapy (Xer12m) and
to test the hypothesis that the ratio of fat-to-functional parotid tissue is
related to Xer12m. Additionally, improvement of the reference Xer12m model based
on parotid gland dose and baseline xerostomia, with MR-IBMs was explored.
METHODS: Parotid gland MR-IBMs of 68 head and neck cancer patients were extracted
from pre-treatment T1-weighted MR images, which were normalized to fat tissue,
quantifying 21 intensity and 43 texture image characteristics. The performance of
the resulting multivariable logistic regression models after bootstrapped forward
selection was compared with that of the logistic regression reference model.
Validity was tested in a small external cohort of 25 head and neck cancer
patients. RESULTS: High intensity MR-IBM P90 (the 90th intensity percentile)
values were significantly associated with a higher risk of Xer12m. High P90
values were related to high fat concentration in the parotid glands. The MR-IBM
P90 significantly improved model performance in predicting Xer12m (likelihood
ratio-test; p = 0.002), with an increase in internally validated AUC from 0.78
(reference model) to 0.83 (P90). The MR-IBM P90 model also outperformed the
reference model (AUC = 0.65) on the external validation cohort (AUC = 0.83).
CONCLUSION: Pre-treatment MR-IBMs were associated to radiation-induced
xerostomia, which supported the hypothesis that the amount of predisposed fat
within the parotid glands is associated with Xer12m. In addition, xerostomia
prediction was improved with MR-IBMs compared to the reference model.
PMID- 29958773
TI - Cascade hydrolysis and fermentation of corn stover for production of high titer
gluconic and xylonic acids.
AB - Simultaneous saccharification and fermentation (SSF) is an efficient fermentation
operation in lignocellulose biorefining. However, SSF may not be applicable when
the pH values of hydrolysis and fermentation do not match, or the strong
intermediate inhibitors on cellulase activity are generated. This study proposed
a cascade hydrolysis and fermentation (CHF) process for cellulosic gluconic acid
fermentation to overcome the inhibition of the intermediate glucono-gamma-lactone
on cellulase activity. The pretreated and detoxified corn stover feedstock was
enzymatically hydrolyzed into hydrolysate slurry, then gluconic acid and xylonic
acid fermentations were directly conducted by inoculating Gluconobacter oxydans
strain without solid/liquid separation. The sugar loss and energy consumption
were effectively avoided by moving the solid/liquid separation into the
fermentation stage. The experiments and the techno-economic analysis show that
the CHF is simple and cost effective fermentation operation when SSF is not
applicable.
PMID- 29958774
TI - High prevalence of systemic rheumatic diseases in women with type 1 diabetes.
AB - BACKGROUND: The prevalence of systemic rheumatic diseases (SRDs) in T1DM has not
been described. METHOD: This observational study compares SRD prevalence across
age, race, and gender in 1,212 adults with T1DM. FINDINGS: There is an age
dependent enrichment of SRDs in women with T1DM: 9.2% prevalence in women overall
and 14% in women over age 50. CONCLUSION: Clinicians taking care of older women
with T1DM should monitor for these SRDs.
PMID- 29958776
TI - Essential tremor plus is more common than essential tremor: Insights from the
reclassification of a cohort of patients with lower limb tremor.
PMID- 29958775
TI - HIV Testing, Positivity, and Receipt of Services among Black, White, and Hispanic
Women Participating in HIV Prevention Programs Funded by the Centers for Disease
Control and Prevention, 2015.
AB - BACKGROUND: Black women who are positive for human immunodeficiency virus (HIV)
are more likely than other HIV-positive women to experience poor health outcomes.
Given these disparities, we compared receipt of HIV testing and other preventive
services among Black, White, and Hispanic women participating in HIV prevention
programs funded by the Centers for Disease Control and Prevention in 2015.
METHODS: Data came from 61 health department jurisdictions and 123 community
based organizations. Using Wald chi2 tests, we assessed racial/ethnic differences
in HIV testing by demographic characteristics, risk factors, HIV status, HIV
service delivery, and (using unlinked data) participation in evidence-based HIV
prevention interventions among women. We also assessed temporal changes in Black
women's receipt of preventive services (2012-2015). RESULTS: In 2015, there were
1,326,589 HIV testing events (single sessions in which one or more HIV tests are
performed to determine HIV status) that occurred among Black, White, and Hispanic
women, resulting in 4,868 positive diagnoses. Proportionally fewer Black (vs.
White and Hispanic) women were linked to HIV medical care within 90 days (64.4%
vs. 69.1% and 73.7%), interviewed for partner services (50.4% vs. 54.4% and
63.5%), and referred to risk reduction services (55.5% vs. 57.7% and 59.8%). From
2012 to 2015, HIV testing events among Black women decreased by 15.2%, but
linkage to care within 90 days increased by 30.6% and participation in one or
more evidence-based intervention increased by 46.8% among HIV-positive Black
women. CONCLUSIONS: Black HIV-positive women were less likely than White and
Hispanic women to receive services that prevent HIV-related morbidity and
mortality. Additional programmatic efforts are needed to increase the proportion
of HIV-positive Black women who are linked to services to reduce HIV disparities
among women.
PMID- 29958777
TI - The Physician Payment Sunshine Act: Evaluating Industrial Payments in Radiology.
AB - RATIONALE AND OBJECTIVES: The characterization of payments made to physicians by
pharmaceutical companies, device manufacturers, and group purchasing
organizations is crucial for assessing potential conflicts of interest and their
impact on practice patterns. This study examines the compensation received by
general radiologists (GR) in the United States, as well as radiologists in the
following five subspecialties: body imaging, neuroradiology, pediatric radiology,
nuclear radiology and radiological physics, and vascular and interventional
radiology. MATERIALS AND METHODS: Data were extracted from the Open Payments
database for radiology subspecialists in the United States who received
installments in calendar year 2015 from pharmaceutical and device manufacturing
companies. RESULTS: In 2015, a total of $43,685,052 was paid in 65,507 payments
(mean $667/payment; median $32/payment) to radiologists, including 9826 GR, 362
body imaging radiologists, 479 neuroradiologists, 127 pediatric radiologists, 175
physicians in nuclear radiology and radiological physics, and 1584 vascular and
interventional radiologists. Payments were unequally distributed across these six
major subspecialties of radiology (p < 0.01), with GR receiving the largest
number of total payments (44,695), and neuroradiologists receiving significantly
higher median payments than any other subspecialty ($80 vs $32 for all
radiologists; p < 0.01). Medtronic Neurovascular was the single largest payer to
all radiologists combined. CONCLUSION: Commercial entities make substantial
payments to radiologists, with a significant variation in payments made to the
different radiology subspecialties. While the largest number of total payments
was made to GGR, the highest median payments were made to neuroradiologists, and
significant dispersion in these payments was seen across different geographic
regions. The impact of these payments on practice patterns remains to be
elucidated.
PMID- 29958778
TI - Long-term effects of intense pulsed light treatment on the ocular surface in
patients with rosacea-associated meibomian gland dysfunction.
AB - PURPOSE: We aimed to determine the long-term effects of intense pulsed light
(IPL) treatment in rosacea-associated meibomian gland dysfunction (MGD). METHODS:
We enrolled 17 rosacea subjects with moderate and severe MGD who underwent four
IPL sessions at 3-week intervals and were followed up for 12 months. The subjects
underwent clinical examinations at baseline (first IPL) and at 3 (second), 6
(third), 9 (fourth), and 12 weeks, as well as 6 and 12 months, after baseline.
Ocular surface parameters, including the Ocular Surface Disease Index (OSDI),
tear break-up time (TBUT), staining score, and noninvasive Keratograph tear break
up time (NIKBUT), as well as meibomian gland parameters, including the lid margin
vascularity and meibum expressibility and quality, were evaluated. RESULTS: All
ocular surface and meibomian gland parameters for all subjects exhibited
significant changes from baseline to the final examination (Friedman, P < 0.050
for all). In particular, improvements in the lower lid margin vascularity, meibum
expressibility and quality, and ocular symptoms persisted up to the final
examination (Wilcoxon, P < 0.050 for all). However, the improvements of TBUT,
staining score, and NIKBUT after IPL were not maintained at 6 and 12 months after
baseline. CONCLUSIONS: In rosacea-associated MGD, four IPL treatments at 3-week
intervals can improve long-term lid parameters and ocular symptoms without
adverse effects.
PMID- 29958779
TI - Blink Test enhances ability to screen for dry eye disease.
AB - AIM: To evaluate the patient-administered OptrexTM Dry Eye Blink Test against
established clinical criteria for the diagnosis of dry eye disease (DED) and to
evaluate its benefit in enhancing screening for DED. METHODS: Eighty-seven
participants aged 38 +/- 17 years, (44 female) were screened for DED using the
Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II)
diagnostic criteria. In addition to symptoms screening with the Ocular Surface
Disease Index questionnaire (>=13 cut-off score for DED), these criteria required
a sign of loss of homeostasis of the tear film in the form of a non-invasive tear
breakup time (NIBUT) <10 s (Oculus Keratograph; K5M), an osmolarity reading >=308
mOsm/L or an interocular difference in osmolarity of >8 (Tearlab), or ocular
surface staining (>5 fluorescein corneal spots, >9 lissamine green spots or lid
wiper staining [>=2 mm length & >=25% width]) to confirm a diagnosis of DED. The
self-administered Blink Test, which requires the participant to observe an image
on a computer screen and report the length of time (in seconds) that they can
refrain from blinking without discomfort, was repeated three times. RESULTS:
Using a cut-off time of 10 s, the Blink Test demonstrated sensitivity of 66%,
specificity of 88%, and an area under the curve of 0.77 (p < 0.001), in
predicting a diagnosis of DED according to the TFOS DEWS II criteria. The
correlation between the Blink Test and NIBUT was r = 0.47 (p < 0.001). When
combined with the screening questionnaire, the sensitivity and specificity of the
Blink Test increased to 71% and 90%, respectively. CONCLUSION: The Blink Test
offers health professionals without advanced instrumentation, as well as
patients, themselves, a rapid method of identifying possible DED.
PMID- 29958780
TI - Combined percutaneous radiofrequency ablation and cementoplasty for the treatment
of extraspinal painful bone metastases: A prospective study.
AB - INTRODUCTION: About 50% of patients with cancer develop bone metastasis mainly
presenting with distressing, drug-resistant pain. AIM OF THE WORK: The study
evaluated efficacy and safety of combined cementoplasty and bony radiofrequency
ablation in palliation of intractable pain and disability in cancer patients with
bony metastases. PATIENTS AND METHODS: The study included 30 adult patients
suffering from localized bony metastases causing refractory moderate to severe
pain. Radiofrequency bony ablation performed followed by cementoplasty were done
under computed tomography (CT) guidance with conscious sedation and local
anesthesia. Final CT check was done to ensure adequate lesion filling and to
exclude any cement leakage. Pain, hemodynamic variables, and neurological status
were checked for a minimum of 2 h before discharge. The patients were followed up
weekly in the pain clinic. The primary outcome measures pain severity and daily
opioid consumption. The secondary outcome measures were quality of life and the
degree of disability, and procedure-related adverse outcomes. RESULTS: Pain
score, daily morphine consumption, and Oswestry Disability Index score decreased
significantly after 1 day, and 1, 4 and 12 weeks. None of the patients had
serious complications during the postoperative follow up visits. Only 4 patients
(13.3%) experienced discomfort during, and few days after the procedure, 3
patients (10%) suffered from local infection, and 2 patients (6.7%) reported
cement leakage. CONCLUSION: Combined radiofrequency ablation and cementoplasty is
a safe and effective pain relief modality in patients suffering from extraspinal
painful bone metastases with improvement of the quality of life.
PMID- 29958781
TI - Nail the Diagnosis.
PMID- 29958793
TI - ACL reconstructed individuals do not demonstrate deficits in postural control as
measured by single-leg balance.
AB - BACKGROUND: Following anterior cruciate ligament reconstruction (ACLR), patients
undergo a battery of performance assessments to determine progression of return
to sport activity. Rates of reinjury following ACLR are high, indicating that
current assessments may not accurately identify deficits at the time point of
return to sport progression. RESEARCH QUESTION: To assess single-leg postural
control in ACLR patients around the time point of return to sport progression and
their relationships to subjective function. STUDY DESIGN: Descriptive Laboratory
Study. METHODS: 198 individuals (108 ACLR, 90 healthy) participated. All ACLR
participants were at the time point of return to play progression. Postural
stability was quantified by center of pressure (COP) average velocity measured
through a straight-knee single-leg balance assessment for 10-seconds with the
participant's eyes closed. Subjective knee function was measured from the
International Knee Documentation Committee (IKDC) Subjective Knee Form and the
Knee Osteoarthritis Outcome Score (KOOS) subscales. RESULTS: No significant
differences existed between COP average velocity between limbs (uninvolved,
involved) or groups (ACLR, Healthy). As a secondary aim, no significant
relationships existed between measures of subjective knee function and postural
stability. SIGNIFICANCE: Individuals following ACLR demonstrate similar patterns
of postural stability as healthy individuals in a straight knee single leg
balance task. Single-leg balance in a straight knee position may not be sensitive
enough to detect impairments and does not predict subjective function in ACLR
patients at the time of return to sport progression.
PMID- 29958796
TI - Cyclophosphamide with or without fluorouracil followed by subcutaneous or
intravenous interleukin-2 use in solid tumors: A feasibility off-label
experience.
AB - BACKGROUND: Immune tolerance seems to correlate with disease progression and T
regulatory cells (Tregs) and myeloid-derived suppressor cells play a relevant
role in immunosuppression. Cyclophosphamide (Cyt) and Fluorouracil (FU) seem to
reduce these cell populations. METHODS AND OBJECTIVE: Establishing safety,
feasibility, activity and impact on the immune system (neutrophil/lymphocyte
[N/L], platelet/L [Plt/L], monocyte [M] and lymphocyte subpopulation (CD3, CD4,
CD8, CD16, HLADR/CD3, Tregs, cells count), CD8/Treg and C-reactive protein (CRP).
TREATMENT: 1) Cyt 300 mg/sqm +/- FU 500 mg/sqm day (d) 1 and interleukin 2 (IL-2)
18 MUI/sqm intravenous (I.V.) d 4-6, 18-20 or 2) Cyt 300 mg/sqm + FU 500 mg/sqm
day d 1, IL-2 4.5 MUI subcutaneous (S.C.) d 3-6, 17-20. The cycle was repeated
every four weeks for 2 cycles. Stable or responding patients (pts) continued
therapy for 3 cycles. RESULTS: From February 2014 to December 2016, 13/14 pre
treated pts (mean 3 lines) with solid tumors were enrolled. Male/Female: 1/1. The
median age and Eastern Cooperative Oncology Group Performance Status (ECOG PS)
was 68 years and 1 respectively. Mean 2 cycles of therapy were administered. G3-4
toxicities presented as diarrhea and bleeding anemia in 2 pts and proteinuria and
erhytroderma in 1pt, respectively. Regarding the hematological profile, a more
reduction in Plt, less decrease of Plt/Ly, and less increase of Treg with I.V.
than S.C. IL-2 administration was observed. However a transient decrease of Treg
on day 7 of first cycle in the I.V. IL-2 was reported. RESPONSE: PR 3 (23%), SD 3
(23%), PD 7 (54%). The response duration was 2+ and 3 months in 2 HCC and 18+
months in the pancreatic cancer (PC). Pathological CR was reported in one HCC
treated with I.V. IL-2. The median progression-free-survival (PFS) and overall
survival (OS) were 1 and 7 months. CONCLUSION: Cyt-FU-IL-2 can be considered
safe, feasible and moderately active in heavily pre-treated pts. Plt, Plt/Ly,
CD8/Treg and a transient Tregs reduction were observed without significative
difference on survival.
PMID- 29958797
TI - Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired
aplastic anemia and myelodysplastic syndromes.
AB - The alarmin family members S100A8 and S100A9 are acute phase inflammation
proteins, but they also have been proposed as biomarkers in many malignant and
non-malignant diseases. In this study, circulating S100A8 and S100A9 homodimers
and S100A8/A9 heterodimers in plasma were systematically investigated by ELISA in
aplastic anemia (AA) and myelodysplastic syndromes (MDS). Plasma was obtained
from 58 severe AA (SAA) and 30 MDS patients, and from 47 age- and sex-matched
healthy donors. In 40 out of the 58 AA subjects, S100A protein levels were
measured before and 6 months after immunosuppressive therapy (IST). No
differences were observed in AA patients at diagnosis compared to healthy
controls for circulating S100A homodimers and heterodimers. After therapy, SAA
responders showed significantly increased circulating S100A8. Non-responding
patients had significantly higher levels of circulating S100A8/A9 compared to
responders and healthy controls, but without variations of S100A8 and S100A9
homodimers. In MDS patients, circulating S100A8 was significantly elevated
compared to those of AA and/or healthy controls. By Pearson correlation analysis
of protein levels and blood counts, multiple correlations were found. However, as
S100A8 and S100A9 are abundantly present in white blood cells and platelets,
correlations with blood counts likely mirror the higher number of cells in the
blood of some patients. In conclusion, our findings indicate that circulating
S100A8 is increased in MDS but not in AA, and that may be useful to distinguish
these diseases in the differential diagnosis of bone marrow failure syndromes.
Clinicaltrials.gov identifiers: NCT00260689, NCT00604201, NCT01328587,
NCT01623167, NCT00001620, NCT00001397.
PMID- 29958798
TI - TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via
Direct Effects on Smooth Muscle Cells.
AB - Intestinal macrophages are critical for gastrointestinal (GI) homeostasis, but
our understanding of their role in regulating intestinal motility is incomplete.
Here, we report that CX3C chemokine receptor 1-expressing muscularis macrophages
(MMs) were required to maintain normal GI motility. MMs expressed the transient
receptor potential vanilloid 4 (TRPV4) channel, which senses thermal, mechanical,
and chemical cues. Selective pharmacologic inhibition of TRPV4 or conditional
deletion of TRPV4 from macrophages decreased intestinal motility and was
sufficient to reverse the GI hypermotility that is associated with chemotherapy
treatment. Mechanistically, stimulation of MMs via TRPV4 promoted the release of
prostaglandin E2 and elicited colon contraction in a paracrine manner via
prostaglandin E receptor signaling in intestinal smooth muscle cells without
input from the enteric nervous system. Collectively, our data identify TRPV4
expressing MMs as an essential component required for maintaining normal GI
motility and provide potential drug targets for GI motility disorders.
PMID- 29958800
TI - Amphiregulin-Producing Pathogenic Memory T Helper 2 Cells Instruct Eosinophils to
Secrete Osteopontin and Facilitate Airway Fibrosis.
AB - Memory T cells provide long-lasting protective immunity, and distinct
subpopulations of memory T cells drive chronic inflammatory diseases such as
asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling
including fibrotic changes. The immunological mechanisms that induce airway
fibrotic changes remain unknown. We found that interleukin-33 (IL-33) enhanced
amphiregulin production by the IL-33 receptor, ST2hi memory T helper 2 (Th2)
cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling
directly reprogramed eosinophils to an inflammatory state with enhanced
production of osteopontin, a key profibrotic immunomodulatory protein. IL-5
producing memory Th2 cells and amphiregulin-producing memory Th2 cells appeared
to cooperate to establish lung fibrosis. The analysis of polyps from patients
with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of
amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and osteopontin
producing eosinophils. Thus, the IL-33-amphiregulin-osteopontin axis directs
fibrotic responses in eosinophilic airway inflammation and is a potential target
for the treatment of fibrosis induced by chronic allergic disorders.
PMID- 29958799
TI - The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome
Induced Inflammation.
AB - Potassium (K+) efflux across the plasma membrane is thought to be an essential
mechanism for ATP-induced NLRP3 inflammasome activation, yet the identity of the
efflux channel has remained elusive. Here we identified the two-pore domain K+
channel (K2P) TWIK2 as the K+ efflux channel triggering NLRP3 inflammasome
activation. Deletion of Kcnk6 (encoding TWIK2) prevented NLRP3 activation in
macrophages and suppressed sepsis-induced lung inflammation. Adoptive transfer of
Kcnk6-/- macrophages into mouse airways after macrophage depletion also prevented
inflammatory lung injury. The K+ efflux channel TWIK2 in macrophages has a
fundamental role in activating the NLRP3 inflammasome and consequently mediates
inflammation, pointing to TWIK2 as a potential target for anti-inflammatory
therapies.
PMID- 29958802
TI - Virus-Induced Interferon-gamma Causes Insulin Resistance in Skeletal Muscle and
Derails Glycemic Control in Obesity.
AB - Pro-inflammatory cytokines of a T helper-1-signature are known to promote insulin
resistance (IR) in obesity, but the physiological role of this mechanism is
unclear. It is also unknown whether and how viral infection induces loss of
glycemic control in subjects at risk for developing diabetes mellitus type 2
(DM2). We have found in mice and humans that viral infection caused short-term
systemic IR. Virally-induced interferon-gamma (IFN-gamma) directly targeted
skeletal muscle to downregulate the insulin receptor but did not cause loss of
glycemic control because of a compensatory increase of insulin production.
Hyperinsulinemia enhanced antiviral immunity through direct stimulation of CD8+
effector T cell function. In pre-diabetic mice with hepatic IR caused by diet
induced obesity, infection resulted in loss of glycemic control. Thus, upon
pathogen encounter, the immune system transiently reduces insulin sensitivity of
skeletal muscle to induce hyperinsulinemia and promote antiviral immunity, which
derails to glucose intolerance in pre-diabetic obese subjects. VIDEO ABSTRACT.
PMID- 29958803
TI - Iron Drives T Helper Cell Pathogenicity by Promoting RNA-Binding Protein PCBP1
Mediated Proinflammatory Cytokine Production.
AB - Iron deposition is frequently observed in human autoinflammatory diseases, but
its functional significance is largely unknown. Here we showed that iron promoted
proinflammatory cytokine expression in T cells, including GM-CSF and IL-2, via
regulating the stability of an RNA-binding protein PCBP1. Iron depletion or Pcbp1
deficiency in T cells inhibited GM-CSF production by attenuating Csf2 3'
untranslated region (UTR) activity and messenger RNA stability. Pcbp1 deficiency
or iron uptake blockade in autoreactive T cells abolished their capacity to
induce experimental autoimmune encephalomyelitis, an animal model for multiple
sclerosis. Mechanistically, intracellular iron protected PCBP1 protein from
caspase-mediated proteolysis, and PCBP1 promoted messenger RNA stability of Csf2
and Il2 by recognizing UC-rich elements in the 3' UTRs. Our study suggests that
iron accumulation can precipitate autoimmune diseases by promoting
proinflammatory cytokine production. RNA-binding protein-mediated iron sensing
may represent a simple yet effective means to adjust the inflammatory response to
tissue homeostatic alterations.
PMID- 29958801
TI - Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration
and Response to Immunotherapy.
AB - The biological and functional heterogeneity between tumors-both across and within
cancer types-poses a challenge for immunotherapy. To understand the factors
underlying tumor immune heterogeneity and immunotherapy sensitivity, we
established a library of congenic tumor cell clones from an autochthonous mouse
model of pancreatic adenocarcinoma. These clones generated tumors that
recapitulated T cell-inflamed and non-T-cell-inflamed tumor microenvironments
upon implantation in immunocompetent mice, with distinct patterns of infiltration
by immune cell subsets. Co-injecting tumor cell clones revealed the non-T-cell
inflamed phenotype is dominant and that both quantitative and qualitative
features of intratumoral CD8+ T cells determine response to therapy.
Transcriptomic and epigenetic analyses revealed tumor-cell-intrinsic production
of the chemokine CXCL1 as a determinant of the non-T-cell-inflamed
microenvironment, and ablation of CXCL1 promoted T cell infiltration and
sensitivity to a combination immunotherapy regimen. Thus, tumor cell-intrinsic
factors shape the tumor immune microenvironment and influence the outcome of
immunotherapy.
PMID- 29958804
TI - Sympathetic Neuronal Activation Triggers Myeloid Progenitor Proliferation and
Differentiation.
AB - There is a growing body of research on the neural control of immunity and
inflammation. However, it is not known whether the nervous system can regulate
the production of inflammatory myeloid cells from hematopoietic progenitor cells
in disease conditions. Myeloid cell numbers in diabetic patients were strongly
correlated with plasma concentrations of norepinephrine, suggesting the role of
sympathetic neuronal activation in myeloid cell production. The spleens of
diabetic patients and mice contained higher numbers of tyrosine hydroxylase (TH)
expressing leukocytes that produced catecholamines. Granulocyte macrophage
progenitors (GMPs) expressed the beta2 adrenergic receptor, a target of
catecholamines. Ablation of splenic sympathetic neuronal signaling using
surgical, chemical, and genetic approaches diminished GMP proliferation and
myeloid cell development. Finally, mice lacking TH-producing leukocytes had
reduced GMP proliferation, resulting in diminished myelopoiesis. Taken together,
our study demonstrates that catecholamines produced by leukocytes and sympathetic
nerve termini promote GMP proliferation and myeloid cell development.
PMID- 29958805
TI - Sleep characteristics that predict atrial fibrillation.
AB - BACKGROUND: The relationship between sleep disruption, independent of obstructive
sleep apnea (OSA), and atrial fibrillation (AF) is unknown. OBJECTIVE: The
purpose of this study was to determine whether poor sleep itself is a risk factor
for AF. METHODS: We first performed an analysis of participants in the Health
eHeart Study and validated those findings in the longitudinal Cardiovascular
Health Study, including a subset of patients undergoing polysomnography. To
determine whether the observed relationships readily translated to medical
practice, we examined 2005-2009 data from the California Healthcare Cost and
Utilization Project. RESULTS: Among 4553 Health eHeart participants, the 526 with
AF exhibited more frequent nighttime awakening (odd ratio [OR] 1.47; 95%
confidence interval [CI] 1.14-1.89; P = .003). In 5703 Cardiovascular Health
Study participants followed for a median 11.6 years, frequent nighttime awakening
predicted a 33% greater risk of AF (hazard ratio [HR] 1.33; 95% CI 1.17-1.51; P
<.001). In patients with polysomnography (N = 1127), every standard deviation
percentage decrease in rapid eye movement (REM) sleep was associated with a 18%
higher risk of developing AF (HR 1.18; 95% CI 1.00-1.38; P = .047). Among
14,330,651 California residents followed for a median 3.9 years, an insomnia
diagnosis predicted a 36% increased risk of new AF (HR 1.36; 95% CI 1.30-1.42; P
<.001). CONCLUSION: Sleep disruption consistently predicted AF before and after
adjustment for OSA and other potential confounders across several different
populations. Sleep quality itself may be important in the pathogenesis of AF,
potentially representing a novel target for prevention.
PMID- 29958806
TI - The 2017 Sachs Lecture: Kindling Knowledge in Epilepsy.
PMID- 29958807
TI - Effects of natural solar UV-B radiation on three Arabidopsis accessions are
strongly affected by seasonal weather conditions.
AB - Large numbers of studies have reported on the responses of plants that are
exposed to a specific dose of ultraviolet-B (UV-B) radiation. However, in the
natural environment UV-B is a highly dynamic variable with UV-B intensities
depending on, amongst others, geographic, temporal, weather and climatic factors.
Furthermore, UV-B effects on plants can potentially be modulated by other
environmental variables, and vice versa. This study aimed to characterize UV-B
effects on plant morphology and accumulation of UV-screening pigments within the
context of an oceanic climate and to assess the potential seasonality of plant UV
B responses. Arabidopsis thaliana was grown outdoors under UV-blocking or
transmitting filters. Genotypic differences in the adaptive response to UV-B were
assessed at seven time-points over a 12 month period and involved the Arabidopsis
accessions Ler, Col-0, and Bur-0. Strong seasonal effects were found on rosette
morphology and total UV-screening pigment concentrations across the three
accessions. Low temperatures were the main determinant of accumulation of UV
absorbing pigments, with no clear UV-B effect observed at any time throughout the
year. There was a significant UV effect on morphology during the summer months,
and this was most likely associated with stress. This study shows that UV-effects
need to be analysed in the context of weather, and other co-occurring natural
factors, and emphasizes the importance of a holistic, multifactorial approach for
the investigation of environmentally relevant UV-effects.
PMID- 29958808
TI - Editorial commentary: Update on cardio-oncology: Novel cancer therapeutics and
associated cardiotoxicities.
PMID- 29958809
TI - Nonvitamin K Oral Anticoagulants in Patients With Atrial Fibrillation and Severe
Renal Dysfunction.
AB - Both atrial fibrillation (AF) and chronic kidney disease (CKD) are highly
prevalent, especially with increasing age and associated comorbidities, such as
hypertension, diabetes, heart failure, and vascular disease. The relationship
between both AF and CKD seems to be bidirectional: CKD predisposes to AF while
onset of AF seems to lead to progression of CKD. Stroke prevention is the
cornerstone of AF management, and AF patients with CKD are at higher risk of
stroke, mortality, cardiac events, and bleeding. Stroke prevention requires use
of oral anticoagulants, which are either vitamin K antagonists (eg, warfarin), or
the nonvitamin K antagonist oral anticoagulants (NOACs). While NOACs have been
shown to be effective in mild-to-moderate renal dysfunction, there are a paucity
of data regarding NOACs in severe and end-stage renal dysfunction. This review
first discusses the evidence for NOACs in CKD. Second, we summarize the current
knowledge regarding the efficacy and safety of NOACs to prevent AF-related stroke
and systemic embolism in severe and end-stage renal disease.
PMID- 29958810
TI - Explant portal vein for reconstructing middle hepatic vein in right lobe living
donor liver transplantation-outcome analysis.
AB - BACKGROUND: The aim of the study was to study the four week patency rates of the
reconstructed neo middle hepatic vein specifically using the explant portal vein
(PV) in right hemiliver live donor liver transplantation (LDLT). We hypothesized
that short term patency of the neo-MHV should result in good graft and patient
outcomes. METHODS: Pre, intra and post operative variables were prospectively
collected for 88 consecutive patients undergoing right hemiliver LDLT from
January 2014 to October 2015. RESULTS: Explant PV was used to reconstruct neo-MHV
in 76 (86.4%, 76/88) patients. Neo MHV patency rate at 28 days with explant PV
was 89.4% (59/66) and with other conduit (PTFE) was 90.9% (10/11). All occlusions
were detected after 7 days. There was no impact of the patency of the neo-MHV on
the incidence of early allograft dysfunction, sepsis, rejection, morbidity or
mortality, despite the contribution of the anterior sector to the graft volume
being more than 50% in close to two-thirds of patients. CONCLUSION: The
reconstructed neo-MHV has excellent short term patency rates at 4 weeks. Perhaps
due to the absence of early occlusions, there was no impact on graft or patient
outcomes in the study population.
PMID- 29958811
TI - Long-term outcomes of patients with intraductal growth sub-type of intrahepatic
cholangiocarcinoma.
AB - BACKGROUND: Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC)
may be associated with a favorable prognosis compared with mass-forming (MF) and
periductal-infiltrating (PI) ICC. METHODS: The clinico-pathological
characteristics and long-term outcomes of 1206 patients undergoing liver
resection for ICC were compared based on the ICC morphological classification.
RESULTS: Compared with MF patients, IG patients had a higher incidence of poor/un
differentiated tumor, lympho-vascular, and perineural invasion (poor/un
differentiated: MF, 18% vs. IG, 24%; lympho-vascular invasion: MF, 30% vs. IG,
35%; perineural invasion: MF, 17% vs. IG, 33%; all p > 0.05). The pattern of
recurrence was different among MF patients (intrahepatic only: 63%; extrahepatic
only: 22%; both intra- and extrahepatic: 16%) versus IG patients (intrahepatic
only: 46%; extrahepatic: 25%; both intra- and extrahepatic: 29%) (p < 0.001).
Moreover, while 78% of patients with MF had an early recurrence (<18 months from
surgery), 59% of IG patients had and early recurrence (p = 0.039). On
multivariable analysis, after controlling for competing risk factors, IG patients
had a similar prognosis as MF patients (HR 0.90, p = 0.69). CONCLUSION: While IG
patients more frequently presented with more adverse pathological
characteristics, the prognosis of IG patients was comparable with MF patients
after controlling for all these adverse factors.
PMID- 29958812
TI - Previous Bevacizumab and Efficacy of Later Anti-Epidermal Growth Factor Receptor
Antibodies in Metastatic Colorectal Cancer: Results From a Large International
Registry.
AB - BACKGROUND: The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI)
plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal
cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus
FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but
improved overall survival (OS). A potential explanation is that the initial
biologic agent administered in metastatic CRC (mCRC) affects later line efficacy
of the other treatments. We sought to test this hypothesis. MATERIALS AND
METHODS: We interrogated our mCRC registry (Treatment of Recurrent and Advanced
Colorectal Cancer) regarding treatment and outcome data for RAS wild-type
patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second
and subsequent lines. Survival outcomes from the beginning of EGFRI use were
determined as a function of previous bevacizumab use and the interval between
ceasing bevacizumab and beginning EGFRI use. RESULTS: Of 2061 patients, 222
eligible patients were identified, of whom 170 (77%) had received previous
bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not
differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12;
P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole
cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P =
.57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right
sided primary tumors when the interval between bevacizumab and EGFRI use was < 6
versus > 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left
sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26). CONCLUSION:
Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The
apparent effect of time between biologic agents in right-sided tumors might
reflect patient selection.
PMID- 29958813
TI - Innovative Surveillance Strategies to Support the Elimination of Filariasis in
Africa.
AB - Lymphatic filariasis (LF) and onchocerciasis are two neglected tropical diseases
(NTDs) of public health significance targeted for global elimination. The World
Health Organization (WHO) African Region is a priority region, with the highest
collective burden of LF and onchocerciasis globally. Coendemic loiasis further
complicates elimination due to the risk of adverse events associated with
ivermectin treatment. A public health framework focusing on health-related data,
systematic collection of data, and analysis and interpretation of data is used to
highlight the range of innovative surveillance strategies required for filariasis
elimination. The most recent and significant developments include: rapid point-of
care test (POCT) diagnostics; clinical assessment tools; new WHO guidelines; open
access online data portals; mHealth platforms; large-scale prevalence maps; and
the optimisation of mathematical models.
PMID- 29958814
TI - Role of the cannabinoid signaling in the brain orexin- and ghrelin-induced
visceral antinociception in conscious rats.
AB - We hypothesized that the cannabinoid (CB) system may mediate the brain orexin- or
ghrelin-induced visceral antinociception. Intraperitoneal injection of either
CB1/2 agonist, WIN 55212 or O-Arachidonoyl ethanolamine increased the threshold
volume of colonic distension-induced abdominal withdrawal reflex in rats,
suggesting CB could induce visceral antinociception. Pretreatment with either the
CB1 or CB2 antagonist potently blocked the centrally injected orexin-A-induced
antinociceptive action against colonic distension while CB2 but not CB1
antagonist blocked the brain ghrelin-induced visceral antinociception. These
results suggest that the cannabinoid signaling may be involved in the central
orexin- or ghrelin-induced antinociceptive action in a different mechanistic
manner.
PMID- 29958815
TI - Using a geriatric oncology assessment to link with services (GOAL).
AB - OBJECTIVE: Geriatric screening tools assess functional limitations and inform
clinical decision-making for older adults with cancer. Our objective was to
evaluate the feasibility and effectiveness of a screener in community-based
oncology clinics. MATERIALS AND METHODS: Eligible patients were from two rural,
underserved community-based cancer clinics; within 12 months of a cancer
diagnosis (breast, lung, colorectal, pancreas, esophageal); aged >=60 years; and
not exclusively pursuing palliative care. We used a previously validated tool
that was embedded in the electronic health record (EHR). Patient-reported
responses identified memory impairment, depressive symptoms, deficits in
activities of daily living, poor nutrition, and polypharmacy. At the discretion
of the oncologist, responses prompted service referrals. From the EHR, we
extracted information about referrals and completion of planned therapy. We
present descriptive statistics. RESULTS: Enrolled patients (n = 44) had a mean
age of 71.5 years (SD = 6.9). Most were non-white (61%), women (66%), with
government-sponsored health insurance (80%). The most commonly identified
geriatric syndromes: polypharmacy (89%), reduced quality of life (39%), and poor
nutrition (39%). The screener triggered a referral in 98% of patients. Generated
referrals were for depressive symptoms (52% needed, 39% received), nutrition (43%
needed, 37% received), and polypharmacy (89% needed, 26% received). Patients were
referred to social work (56%), nutrition (44%), and pharmacy (25%). Many patients
completed planned radiation therapy (100%), surgery (70%), and chemotherapy
(60%). CONCLUSIONS: Use of an EHR-embedded brief geriatric oncology assessment in
rural oncology clinics identified geriatric syndromes that would benefit from
provision of services in nearly all enrolled patients. TRIAL REGISTRATION:
ClinicalTrials.gov Identifier: NCT02906592.
PMID- 29958817
TI - Evaluation of local instillation of antibiotics in infected walled-off pancreatic
necrosis.
AB - BACKGROUND: Infected walled-off pancreatic necrosis (WON) is associated with
increased morbidity and mortality. Systemic antibiotics are the main treatment,
but are associated with adverse reactions and risk of superinfections. This study
evaluates the efficacy of local instillation of antibiotics into WON. METHODS: We
performed a retrospective cohort study of all consecutive patients with infected
WON, who were treated with endoscopic transmural drainage and necrosectomy (ETDN)
at a tertiary referral hospital between 2012 and 2016. A total of 91 patients
were included. Patients often received concomitant intravenous and local
antibiotics. Local antibiotics were added to the irrigation fluid depending on
microbiological findings. A beneficial response was defined as the eradication of
a microbe on subsequent culturing. Univariable and multivariable logistic
regression analyses were used to evaluate antimicrobial efficacy. RESULTS: At the
first drainage 81 (86%) patients had infected and 10 sterile WON. Among patients
with bacterial infections, neither local nor systemic antibiotics were associated
with the eradication of microbes between first and second culture. Between the
second and third culture, the use of local antibiotics was associated with the
eradication of microbes (OR, 2.54; 95% CI, 1.25-5.18; p = 0.01), but not systemic
antibiotics (OR, 0.75; 95% CI, 0.38-1.38; p = 0.33). Twelve patients had fungal
infections treated with local amphotericin B between first and second culture.
The fungus was eradicated in all 12 patients. CONCLUSION: Local instillation of
antibiotics may be a promising supplement to systemic administration.
PMID- 29958818
TI - Effects of Geriatric Team Rehabilitation After Hip Fracture: Meta-Analysis of
Randomized Controlled Trials.
AB - OBJECTIVE: Systematic rehabilitation by geriatric interdisciplinary teams has
been associated with favorable outcomes in frail older patients. The aim of the
present meta-analysis was to evaluate the effects of interdisciplinary geriatric
team rehabilitation in older patients with hip fracture. DESIGN, SETTING, AND
PARTICIPANTS: Randomized controlled trials involving participants sustaining hip
fractures at the age of 65 years or older were included. Included trials
evaluated effects of interdisciplinary geriatric team rehabilitation compared
with usual postoperative care and reported on at least one of the following
outcomes: activities of daily living (ADLs), physical function, mobility,
depression, cognitive function, discharge to home, quality of life, influence on
relatives, complications, and survival. Seven studies of at least moderate
quality with a total of 1763 participants were included. MEASURES: Data were
combined using a random-effects model. The GRADE system (1-4, where 4 is highest
level of evidence) was used to rate the quality of the estimates. RESULTS:
Outcomes were grouped into 4 categories, each of which was reported on in at
least 4 studies: ADL/physical function, mobility, living in one's own home, and
survival. Interdisciplinary geriatric team rehabilitation increased ADL/physical
function (standardized mean difference [SMD], 0.32; 95% confidence interval [CI],
0.17-0.47) and mobility (SMD, 0.32; 95% CI, 0.12-0.52) compared with conventional
care. In contrast, interdisciplinary geriatric team rehabilitation did not
increase the chance of living in one's own home after discharge (risk ratio [RR],
1.07; 95% CI, 0.99-1.16) or survival (RR, 1.02; 95% CI, 0.99-1.06) compared with
conventional care. All results were rated as GRADE 3. CONCLUSION: Systematic
rehabilitation by geriatric interdisciplinary teams increases physical function
and mobility significantly compared with conventional care in patients with hip
fracture. In contrast, the chance of being discharged to one's own home and
survival are not influenced.
PMID- 29958819
TI - [Down's syndrome and primary health care].
PMID- 29958820
TI - Cellular and molecular approaches to enhance myocardial recovery after myocardial
infarction.
AB - Reperfusion therapy has resulted in significant improvement in post-myocardial
infarction morbidity and mortality in over the last 4 decades. Nonetheless, it is
well recognized that simply restoring patency of the epicardial artery may not
stop or reverse damage at microvascular level, and myocardial salvage is often
suboptimal. Numerous efforts have been undertaken to elucidate the mechanisms
underlying extensive myonecrosis to facilitate the discovery of therapies to
provide additional and incremental benefits over current therapeutic pathways. To
date, conclusively effective strategies to promote myocardial recovery have not
yet been established. Novel approaches are investigating the foundational
cellular and molecular bases of myocardial ischemia and irreversible injury.
Herein, we review the emerging concepts and proposed therapies that may improve
myocardial protection and reduce infarct size. We examine the preclinical and
clinical evidence for reduced infarct size with these strategies, including anti
inflammatory agents, intracellular ion channel modulators, agents affecting the
reperfusion injury salvage kinase (RISK) and nitric oxide signaling pathways,
modulators of mitochondrial function, anti-apoptotic agents, and stem cell and
gene therapy. We review the potential reasons of failures to date and the
potential for new strategies to further promote myocardial recovery and improve
prognosis.
PMID- 29958821
TI - Wide-field Choroidal Vascularity in Healthy Eyes.
AB - PURPOSE: To report variation of choroidal vascularity index (CVI) in macular and
mid-equator areas in healthy subjects using wide-field optical coherence
tomography (WF-OCT). DESIGN: Prospective, cross-sectional study. METHODS:
Setting: Two-center study. STUDY POPULATION: Twenty eyes of 20 healthy subjects.
OBSERVATION PROCEDURE: Single high-definition scans passing through the fovea in
both vertical and horizontal meridians were studied. Images were taken in primary
gaze and extremes of gaze and a manual montage was created. A previously reported
semi-automated algorithm was used to calculate the CVI in macular, superior,
inferior, temporal, and nasal quadrants. MAIN OUTCOME MEASURES: Difference in CVI
in macular area and 4 quadrants. RESULTS: Twenty eyes from 20 subjects were
enrolled in the study. The mean age was 28.85 +/- 6.29 years with men comprising
9 of the 20 subjects (45.0%). The refractive error (spherical equivalent) ranged
from -3.00 to +0.75 diopters. The average CVI in the macular area (40.01 +/-
7.67) was significantly smaller than in any of the other fundus areas (all P <
.01). The maximum CVI was seen in the nasal quadrant (50.84 +/- 5.64), followed
by inferior (47.93 +/- 9.31), temporal (46.14 +/- 7.06), and superior (45.72 +/-
7.69). The nasal quadrant was found to have the least coefficient of variation
(CV) of CVI (0.11) while the inferior and macular area had the highest CV (0.19).
CONCLUSIONS: We report CVI in WF-OCT in healthy young individuals. CVI seems to
have a wide topographic variation. The macular area had the least CVI. CVI values
are more consistent with lesser CV in the nasal quadrant compared to the other
quadrants and macular area.
PMID- 29958822
TI - A statistical shape model to predict the premorbid glenoid cavity.
AB - BACKGROUND: This study proposes a method for inferring the premorbid glenoid
shape and orientation of scapulae affected by glenohumeral osteoarthritis (OA) to
inform restorative surgery. METHODS: A statistical shape model (SSM) built from
64 healthy scapulae was used to reconstruct the premorbid glenoid shape based on
anatomic features that are considered unaffected by OA. First, the method was
validated on healthy scapulae by quantifying the accuracy of the predicted shape
in terms of surface distance, glenoid version, and inclination. The SSM-based
reconstruction was then applied to 30 OA scapulae. Glenoid version and
inclination were measured fully automatically and compared between the original
OA glenoids, SSM-based glenoid reconstructions, and healthy scapulae. RESULTS:
Validation on healthy scapulae showed a root-mean-square surface distance between
original and predicted glenoids of 1.0 +/- 0.2 mm. The prediction error was 2.3
degrees +/- 1.8 degrees for glenoid version and 2.1 degrees +/- 2.0 degrees
for inclination. When applied to an OA dataset, SSM-based reconstruction restored
average glenoid version and inclination to values similar to the healthy
situation. No differences were observed between average orientation values
measured on SSM-based reconstructed and healthy scapulae (P >= .10). However, the
average orientation of the reconstructed premorbid glenoid differed from the
average orientation of OA glenoids for Walch classes A1 (version) and B2
(version, inclination, and medialization). CONCLUSION: The proposed SSM can
predict the premorbid glenoid cavity of healthy scapulae with millimeter
accuracy. This technique has the potential to reconstruct the premorbid glenoid
cavity shape, as it was prior to OA, and thus to guide the positioning of glenoid
implants in total shoulder arthroplasty.
PMID- 29958823
TI - Skin cells for use in an alternate diagnostic method for Duchenne muscular
dystrophy.
AB - The importance of molecular diagnosis and identification of disease-associated
variants for Duchenne muscular dystrophy (DMD) is evident in the age of gene
based therapies and personalised medicine. Detection of the causative DMD variant
and determination of its effects on dystrophin expression is best achieved by
analysis of RNA extracted from muscle biopsy material. However, this is not done
routinely, as the procedure can be traumatic, especially to young children, and
carries risk of complications related to the use of anaesthetic. As skin biopsies
are safer and straightforward to perform than muscle biopsies, we investigated
the utility of cultured human epidermal melanocytes and dermal fibroblasts as
alternative tools for RNA-based diagnosis of DMD. Shallow skin biopsies from 5
boys with genetically confirmed diagnoses of DMD were used to culture fibroblasts
and melanocytes. Biopsies were sampled, and tolerated without complications,
using local anaesthetic cream. Dystrophin expression in the cultured cells was
assessed using immunocytochemical staining, quantitative real-time PCR and cDNA
sequencing methodologies. We observed differential expression of the full-length
dystrophin muscle transcript, with significantly more robust expression in
melanocytes, compared to that in fibroblasts. Our results suggest that cultured
skin melanocytes may present an alternative tool for RNA-based genetic diagnosis
of DMD.
PMID- 29958824
TI - Crop quality under rising atmospheric CO2.
AB - Crops grown under elevated CO2 (eCO2) typically exhibit enhanced yields but at
the same time decreased nutritional quality. The latter effect has often been
explained as a growth dilution phenomenon, but this cannot be the only process
involved since crop nutrient concentrations are decreased also when production is
unaffected by eCO2. We review the current knowledge on eCO2 effects on crop
nutritional quality with focus on the current understanding of the possible
mechanisms and processes causing these effects. Emphasis is on crop nitrogen (N)
and protein concentrations but effects on other nutrients and how they compare
with those on N are also covered.
PMID- 29958825
TI - Thrombopoietin receptor agonists and risk of portal vein thrombosis in patients
with liver disease and thrombocytopenia: A meta-analysis.
AB - BACKGROUND: Treatment of thrombocytopenia with thrombopoietin receptor agonists
(TPORAs) seems to be associated with portal vein thrombosis (PVT) in patients
with chronic liver disease (CLD). We performed a meta-analysis of the trials
carried out in this clinical setting to assess if such association is detectable.
METHODS: We performed a meta-analysis with studies that compared the effect of
TPORAS vs placebo in patients with CLD and thrombocytopenia. RESULTS: Four
studies, including 1953 patients, reported the incidence of PVT in patients with
CLD and thrombocytopenia treated with TPORAs or placebo. No significant
difference was found for incidence of PVT in patients treated with TPORAs
compared with placebo (O.R.: 2.8; 95% C.I., 0.97-8.16; p = 0.055). A significant
association between PVT and TPORAs was observed only in patients treated with
eltrombopag (O.R.: 3.8; 95% C.I., 1.14-13.2; p = 0.03). Three studies, including
514 patients who were undergoing an elective invasive procedure, analyzed the
incidence of PVT in TPORAs-treated patients with CLD and thrombocytopenia; no
significant difference was found for incidence of PVT in patients treated with
TPORAs compared with placebo (O.R.: 2.6; 95% C.I., 0.6-11.6; p = 0.212). A
significant difference was found for incidence of arterial and venous thrombo
embolic events in CLD patients treated with eltrombopag compared with placebo
treated patients (O.R.: 3.4; 95% C.I., 1.5-7.7; p = 0.003). CONCLUSION: The
results of this meta-analysis show that TPORAs are not associated with PVT in CLD
patients even in the case of surgical procedure. PVT risk seems to be associated
only with eltrombopag use.
PMID- 29958826
TI - The role of cardiolipin in promoting the membrane pore-forming activity of BAX
oligomers.
AB - BCL-2-associated X (BAX) protein acts as a gatekeeper in regulating mitochondria
dependent apoptosis. Under cellular stress, BAX becomes activated and transforms
into a lethal oligomer that causes mitochondrial outer membrane permeabilization
(MOMP). Previous studies have identified several structural features of the
membrane-associated BAX oligomer; they include the formation of the BH3-in-groove
dimer, the collapse of the helical hairpin alpha5-alpha6, and the membrane
insertion of alpha9 helix. However, it remains unclear as to the role of lipid
environment in determining the conformation and the pore-forming activity of the
BAX oligomers. Here we study molecular details of the membrane-associated BAX in
various lipid environments using fluorescence and ESR techniques. We identify the
inactive versus active forms of membrane-associated BAX, only the latter of which
can induce stable and large membrane pores that are sufficient in size to pass
apoptogenic factors. We reveal that the presence of CL is crucial to promoting
the association between BAX dimers, hence the active oligomers. Without the
presence of CL, BAX dimers assemble into an inactive oligomer that lacks the
ability to form stable pores in the membrane. This study suggests an important
role of CL in determining the formation of active BAX oligomers.
PMID- 29958827
TI - Molecular heterogeneity of Rhipicephalus sanguineus sensu lato and screening for
Ehrlichia canis in mainland Portugal.
AB - The present study aimed to expand knowledge regarding the molecular
characterization of R. sanguineus s.l. in Portugal and to screen for ticks
naturally infected with E. canis. A total of 113 R. sanguineus s.l. were
collected questing or attached to domestic and wild animals from the 18
administrative regions of mainland Portugal. All the ticks were analyzed for the
16S rRNA and the partial sequences obtained showed high genetic similarities with
specimens belonging to the temperate lineage. These sequences revealed eight
haplotypes (H1-H8), with a genetic distance ranging from 0.3% to 1.4%. A
convenience sample representing approximately 75% of all the R. sanguineus s.l.
ticks collected was tested for the presence of E. canis by qPCR for the dsb gene.
No ticks were found to be infected with this pathogen. Accordingly, further
studies are required to determine the role of the R. sanguineus s.l. temperate
lineage in E. canis maintenance and transmission, as well as to elucidate if a
different R. sanguineus s.l. lineage or other tick species act as E. canis
vectors for dogs in Portugal.
PMID- 29958828
TI - Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis
and acidic pH.
AB - Stimulation of the cytosolic NAD+ dependent deacetylase SIRT1 is cardioprotective
against ischemia-reperfusion (IR) injury. NAD+ precursors including nicotinamide
mononucleotide (NMN) are thought to induce cardioprotection via SIRT1. Herein,
while NMN protected perfused hearts against IR (functional recovery: NMN 42 +/-
7% vs. vehicle 11 +/- 3%), this protection was insensitive to the SIRT1 inhibitor
splitomicin (recovery 47 +/- 8%). Although NMN-induced cardioprotection was
absent in Sirt3-/- hearts (recovery 9 +/- 5%), this was likely due to enhanced
baseline injury in Sirt3-/- (recovery 6 +/- 2%), since similar injury levels in
WT hearts also blunted the protective efficacy of NMN. Considering alternative
cardiac effects of NMN, and the requirement of glycolysis for NAD+, we
hypothesized NMN may confer protection in part via direct stimulation of cardiac
glycolysis. In primary cardiomyocytes, NMN induced cytosolic and extracellular
acidification and elevated lactate. In addition, [U-13C]glucose tracing in intact
hearts revealed that NMN stimulated glycolytic flux. Consistent with a role for
glycolysis in NMN-induced protection, hearts perfused without glucose (palmitate
as fuel source), or hearts perfused with galactose (no ATP from glycolysis)
exhibited no benefit from NMN (recovery 11 +/- 4% and 15 +/- 2% respectively).
Acidosis during early reperfusion is known to be cardioprotective (i.e., acid
post-conditioning), and we also found that NMN was cardioprotective when
delivered acutely at reperfusion (recovery 39 +/- 8%). This effect of NMN was not
additive with acidosis, suggesting overlapping mechanisms. We conclude that the
acute cardioprotective benefits of NMN are mediated in part via glycolytic
stimulation, with the downstream protective mechanism involving enhanced ATP
synthesis during ischemia and/or enhanced acidosis during reperfusion.
PMID- 29958829
TI - Tricuspid Annular Geometry and Strain After Suture Annuloplasty in Acute Ovine
Right Heart Failure.
AB - BACKGROUND: Tricuspid valve repair using suture annuloplasty is thought to be
more physiologic, but the effect of annular reduction on annular geometry and
motion is unknown. We set out to investigate the effect of DeVega suture
annuloplasty (DV) on tricuspid annular geometry and dynamics during acute right
heart failure (RHF). METHODS: Ten adult sheep underwent implantation of
sonomicrometry crystals around the tricuspid annulus and on the right ventricle;
pressure transducers were placed in right ventricle, left ventricle, and right
atrium. RHF was induced by a combination of 500 mL volume infusion, posterior
descending artery occlusion, and pulmonary artery constriction. Hemodynamic,
echocardiographic, and sonomicrometry data were acquired at baseline, with RHF,
and after two progressive (8 to 10 mm) DV suture cinches (DV-1, DV-2) during RHF.
Annular size, geometry, and dynamics were determined from crystal coordinates.
RESULTS: Combination of volume infusion, ischemia, and pulmonary hypertension
resulted in acute RHF and significant functional tricuspid regurgitation grade
(0.5 +/- 0.5 versus 2.7 +/- 0.8, p < 0.001). Annular area increased with RHF from
700 +/- 98 mm2 to 801 +/- 128 mm2 (p < 0.001). DV-1 and DV-2 reduced annular area
to 342 +/- 88 mm2 and 180 +/- 57 mm2 while reducing regurgitation grade to 1.2 +/
0.4 and 0.4 +/- 0.5, respectively (all p < 0.001 versus RHF). Tricuspid annular
area contraction was 12% +/- 7%, 10% +/- 6%, and 12% +/- 6% for RHF, DV-1, and DV
2, respectively (p = 0.25) and annular height was 4.9 +/- 2.0 mm, 5.6 +/- 1.4 mm,
and 5.5 +/- 1.7 mm (p = 0.43). Mean transvalvular gradient was 1.3 +/- 0.7 mm Hg
and 2.0 +/- 1.0 mm Hg with DV-1 and DV-2, respectively. CONCLUSIONS: During acute
ovine RHF, DeVega annuloplasty successfully treated tricuspid regurgitation and
preserved normal tricuspid annular dynamics and geometry. These data may lead to
more physiologic tricuspid reparative techniques.
PMID- 29958830
TI - Invited Commentary.
PMID- 29958831
TI - Corrections.
PMID- 29958832
TI - What Are the Expected Findings on Follow-up Computed Tomography Angiogram in Post
traumatic Patients With Blunt Cerebrovascular Injury?
AB - PURPOSE: Blunt cerebrovascular injury (BCVI) is a rare but potentially
devastating diagnosis. Our study establishes the temporal changes and findings on
follow-up imaging. METHODS: For this retrospective, institutional review board
approved study, the hospital trauma registry was queried for all severely injured
polytrauma patients who underwent computed tomography angiogram (CTA) scans in
the emergency department between January 1, 2010, and December 31, 2016, with
injury severity score >=16, yielding 3747 patients. A total of 128 patients had a
follow-up CTA for BCVI. The grade, location, and outcomes of injuries on follow
up imaging were studied. RESULTS: A vehicular collision was the most common
mechanism of injury (75%). The majority of patients (61%) had a Glasgow Coma
Scale of 10-15. Vertebral fractures were the most common associated injury (57%).
The overall incidence of BCVI in our study population was 4.8%. On the initial
CTA, 50% of injuries were grade 1, 25.4% were grade 2, 7% were grade 3, 17% were
grade 4, and 0.6% were grade 5. For the different grades of injuries, improvement
has been documented in 44% with complete healing in 34%, while 51% of injuries
remained unchanged from the initial scan. Only 5% progressed to a higher-grade
injury. Twelve patients developed strokes with an incidence of 9.4% in patients
with a follow-up CTA. CONCLUSIONS: This study can help increase the awareness of
radiologists about the evolution patterns of different grades of BCVIs on follow
up CTA for severely injured posttraumatic patients.
PMID- 29958833
TI - Use of Breast Magnetic Resonance Imaging in Women Diagnosed With Atypical Ductal
Hyperplasia at Core Needle Biopsy Helps Select Women for Surgical Excision.
AB - PURPOSE: The study sought to investigate the role of breast magnetic resonance
imaging (MRI) in patients diagnosed with atypical ductal hyperplasia (ADH) at
core needle biopsy (CNB). METHODS: The breast MRI database at our centre was
queried for studies performed between January 2010 and December 2016 for the
clinical indication of ADH diagnosed at CNB. Medical files were reviewed for
demographic data, clinical information, and radiology and pathology reports.
Pathological results of the surgical specimens were considered the gold standard
for comparison with breast MRI findings. In women not undergoing excision, at
least 2 years of follow-up was used to ascertain the benign nature of the
finding. RESULTS: Fifty patients were included in the study. Thirty-one (62%)
patients had surgical excision of the ADH lesion, and 7 (23%) were upgraded to
malignancy. Breast MRI accurately identified 6 of the 7 cases. Six of the 12
women (50%) with positive MRI findings at the biopsy site were upgraded to
malignancy on surgical pathology, compared with only 1 of 19 (5%) with negative
MRI findings. Forty-nine percent of the women with a negative MRI did not undergo
surgical excision of the ADH lesion, compared with 8% of the women with a
positive MRI (P = .009), with no cancer diagnosed during follow-up. The
sensitivity, specificity, negative predictive value, and positive predictive
value of breast MRI for predicting upgrade to malignancy were 86%, 83%, 97%, and
46%, respectively. CONCLUSIONS: MRI may have a role in the management of women
diagnosed with ADH on CNB, to minimize diagnostic excisional biopsies.
PMID- 29958834
TI - Imaging Approach to the Diagnosis of Acute Appendicitis in a Group of Teaching
Hospitals With 24/7 In-house Availability of Ultrasound Technologist: Effect of
Timing of Request on Imaging Modality.
AB - PURPOSE: The study sought determine effect of requisition timing on the initial
choice imaging modality in appendicitis evaluation. METHODS: This was an
institutional review board-approved retrospective study, encompassing 3
University of Toronto teaching hospitals, offering 24/7 radiology coverage. All
surgically proven appendicitis cases, from 2012-2014, were included and
presurgical ultrasound (US) or computed tomography (CT) reports were analysed.
Examinations were all requested by the emergency department, performed by the
same technologists and reviewed or finalized by the same radiology group
(residents fellows or attending). Two coverage categories, namely regular hours
(8 am-5 pm, Monday-Friday) or after hours (5 pm-8 am, Monday-Friday and weekends)
were compared. The percentage of the starting modality (US or CT), the rate of CT
following an indeterminate US, and the sensitivity of each modality was compared
between the 2 categories, utilising Mann-Whitney U and chi-square tests. RESULTS:
Presurgical US or CT studies of 494 patients, from February 2012-August 2014,
were evaluated. Regular-hours and after-hours coverage demonstrated 174 (89:85
women:men) and 320 (141:179 women:men; P < .04) patients. The average age, 37.9
+/- 17.1 women versus 35.2 +/- 13.7 men was not statistically different (P = .8).
Regular hours included 89 of 174 (51.1%) of US-only examinations, 50 of 174 (29%)
of CT-only examinations, and 35 of 174 (20%) of US examinations followed by CT
examinations. After hours included 147 of 320 (46%) of US-only examinations, 147
of 320 (46%) of CT-only examinations, and 26 of 320 (8%) of US examinations
followed by CT examinations (P < .001). The total diagnostic sensitivities for US
and CT were 86% (81% regular hours, 90% after hours; P = .041) and 99.2% (100%
regular hours, 99% after hours; P > .05), respectively. CONCLUSIONS: US was less
utilised in acute appendicitis detection after hours, although its diagnostic
sensitivity was better than regular-hours coverage.
PMID- 29958835
TI - [Antenatal diagnosis of an umbilical cord hemangioma].
PMID- 29958836
TI - Systematic analysis of GSK-3 signaling pathways in aging of cerebral tissue.
AB - Glycogen synthase kinase-3 (GSK-3) is a constitutively active kinase, involved in
regulation of multiple physiological processes. In brain, changes in GSK-3
signaling are related to neurodegenerative issues, including Alzheimer's disease.
Due to the wide range of GSK-3 cellular targets, a therapeutic use of the enzyme
inhibitors entails significant risk of side effects. Thus, altering the ratio of
specific pool of GSK-3 or specific substrates instead of changing the global
activity of GSK-3 in brains might be a more appropriate strategy. This paper
provides a comprehensive data on abundances of proteins involved in GSK-3
signaling in three regions of young and old mouse brains. It might help to
identify novel protein targets with the highest therapeutic potential for
treatment of age-related neurodegenerative diseases.
PMID- 29958837
TI - Tumour suppressor properties of miR-15a and its regulatory effects on BCL2 and
SOX2 proteins in colorectal carcinomas.
AB - OBJECTIVES: In this study, we aimed to investigate the expression pattern,
clinicopathological significance and tumour suppressive properties of miR-15a in
patients with colorectal carcinomas. METHODS: Tissue samples from 87 patients
with primary colorectal carcinomas, 50 matched metastatic lymph node and 37 non
neoplastic colon (control) were prospectively recruited. The expression level of
miR-15a was measured by quantitative real-time polymerase chain reaction.
Restoration/overexpression of the miR-15a was achieved by exogenous transfection.
Four colon cancer cell lines (SW480, CaCO2, SW48 and HCT116) and a non-cancer
colon cell line (FHC) were also used for examining the miR-15a induced tumour
suppression properties using various in-vitro and immunological assays. RESULTS:
Downregulation of miR-15a was noted in ~ 62% of the colorectal carcinoma tissues
and it was positively correlated with the presence of cancer recurrence in
patients with colorectal carcinomas (p = 0.05). Also, these patients with low miR
15a expression showed relatively shorter survival time when compared to those
with miR-15a overexpression. Following miR-15a exogenous overexpression, colon
cancer cells showed reduced cell proliferation, low colony formation, less cell
invasion properties and mitochondrial respiration when compared to control cells.
In addition, BCL2 and SOX2 proteins showed a significant downregulation following
miR-15a overexpression suggesting its regulatory role in cancer growth, apoptosis
and stemness. CONCLUSION: This study has confirmed the tumour suppressor
properties of miR-15a in colorectal cancers. Therefore, its modulation has
potential implications in controlling various biological and pathogenic processes
in colon carcinogenesis via targeting its downstream proteins such as BCL2 and
SOX2.
PMID- 29958838
TI - Seasonal time-loss match injury rates and burden in South African under-16 rugby
teams.
AB - OBJECTIVES: Youth rugby union is a popular sport with a high injury incidence
density (IID) and burden. This high risk has called for further research into the
factors affecting the injuries in youth rugby. The aim of the study was to
analyse time-loss IID and burden in multiple schoolboy rugby teams over a season
and the potential factors associated with injury. DESIGN: Prospective cohort
METHODS: All time-loss injuries were recorded from three schools for the whole
season. Overall IID and injury burden were calculated, as well as for injury
event, type, location and the match quarter in which they occurred and Poisson
regression analyses were performed to determine differences. RESULTS: IID was
28.8 (18.9-38.6) injuries per 1000 player hours over the season, with an injury
burden of 379.2 (343.6-414.9) days lost per 1000 player hours. The ball-carrier
had a significantly higher IID (11.3 (5.2-17.5) per 1000 player hours) compared
to other events, and the joint (non-bone)/ligament injuries were the most common
(IID of 12.2 (5.8-18.6) per 1000 player hours) and severe type of injury (burden
of 172.6 (148.5-196.6) days lost per 1000 player hours). CONCLUSIONS: The IID was
similar to previous youth rugby studies, however the injury burden was much
lower. The South African youth cohort showed similar factors associated with
injury for inciting event (the tackle) and injury type (joint (non
bone)/ligament) and location (lower limb) as seen in other studies in both youth
and senior players.
PMID- 29958839
TI - The influence of match characteristics and experience on decision-making
performance in AFL umpires.
AB - OBJECTIVES: The purpose of this study was to investigate the effects of match
characteristics and elite level umpiring experience on the decision-making
performance of umpires in the Australian Football League (AFL). DESIGN: Cross
Sectional Study. METHODS: All decisions from the 2014 AFL home and away season
made by 32 male AFL field umpires (age 33.1+/-5.0years, AFL umpire experience
122+/-105 matches) were classified by a panel of four expert umpire coaches into
correct, missed and unwarranted categories. The 8001 decisions were then further
categorised based on the match time, score differential, field location, home
ground advantage, match attendance and elite level umpiring experience. Chi
square with standardised residuals and two-way analysis of variance were used to
analyse the data. RESULTS: Higher elite level umpiring experience and a larger
score differential at the time of the decision resulted in improved decision
making accuracy. Home ground advantage, attendance and match time did not
influence the decision-making performance of umpires. Impact averse decisions
occurred in the back line of play, with umpires tending to be conservative with
decisions that may impact the score. CONCLUSIONS: Decisions that have an
increased influence on an umpire's decision-making performance include score
differential and elite umpiring experience. Implications on umpiring performance
regarding the venue, attendance and the duration of a match were not apparent.
PMID- 29958840
TI - A multi-year injury epidemiology analysis of an elite national junior tennis
program.
AB - OBJECTIVES: To profile multi-year injury incidence and severity trends in elite
junior tennis players from a national program. DESIGN: Prospective cohort.
METHODS: Injury data was collated by sex, age and region for all nationally
supported Australian junior players (58m, 43f 13-18y) between 2012-2016. Injury
was defined as a physical complaint from training/matchplay interrupting
training/matchplay determined by presiding physiotherapists and doctors. Severity
represented the days of interrupted training/matchplay per injury. Injury
incidence was reported per 1000 exposure hours. Incidence rate change and rate
ratios (RR) +/-95% confidence intervals were used to assess changes over time.
RESULTS: No difference in male and female injury incidence existed (2.7+/-0.0 v
2.8+/-0.0) yet male injuries were more severe (3.6+/-0.6 v 1.1+/-0.9 days). The
lumbar spine was the most commonly and severely injured region in both sexes
(4.3+/-0.2, 9.9+/-1.4d). Shoulder injuries were the second most common in both
sexes (3.1+/-0.2) and with the second highest severity in males (7.3+/-1.4d).
Knee injuries were also common in males (2.3+/-0.2) yet potentially reduced over
time (0.4+/-0.6 RR) as pelvis/buttock injuries increased (3.4+/-14.0 RR). Females
had high trunk and abdominal injury incidences (2.5+/-0.3). Independent of sex,
the injury incidence increased with age from 2.0+/-0.1 (13y) to 2.9+/-0.1 (18y).
CONCLUSIONS: Despite no sex-based difference in injury incidence, male injuries
resulted in more interrupted days of training/matchplay. The lumbar spine and
shoulder were the most commonly injured body regions in both sexes. The number of
injuries sustained by players also increased as they aged.
PMID- 29958841
TI - Interactions of endocannabinoid virodhamine and related analogs with human
monoamine oxidase-A and -B.
AB - The endocannabinoid system plays an important role in the pathophysiology of
various neurological disorders, such as anxiety, depression, neurodegenerative
diseases, and schizophrenia; however, little information is available on the
coupling of the endocannabinoid system with the monoaminergic systems in the
brain. In the present study, we tested four endocannabinoids and two anandamide
analogs for inhibition of recombinant human MAO-A and -B (monoamine oxidase).
Virodhamine inhibited both MAO-A and -B (IC50 values of 38.70 and 0.71 MUM,
respectively) with ~55-fold greater inhibition of MAO-B. Two other
endocannabinoids (noladin ether and anandamide) also showed good inhibition of
MAO-B with IC50 values of 18.18 and 39.98 MUM, respectively. Virodhamine was
further evaluated for kinetic characteristics and mechanism of inhibition of
human MAO-B. Virodhamine inhibited MAO-B (Ki value of 0.258 +/- 0.037 MUM)
through a mixed mechanism/irreversible binding and showed a time-dependent
irreversible mechanism. Treatment of Neuroscreen-1 (NS-1) cells with virodhamine
produced significant inhibition of MAO activity. This observation confirms
potential uptake of virodhamine by neuronal cells. A molecular modeling study of
virodhamine with MAO-B and its cofactor flavin adenine dinucleotide (FAD)
predicted virodhamine's terminal -NH2 group to be positioned near the N5 position
of FAD, but for docking to MAO-A, virodhamine's terminal -NH2 group was far away
(~6.52 A) from the N5 position of FAD, and encountered bad contacts with nearby
water molecules. This difference could explain virodhamine's higher potency and
preference for MAO-B. The binding free energies for the computationally-predicted
poses also showed that virodhamine was selective for MAO-B. These findings
suggest potential therapeutic applications of virodhamine for the treatment of
neurological disorders.
PMID- 29958842
TI - A new method for mild blepharoptosis correction using orbital septum.
PMID- 29958843
TI - Quantitative dynamic analysis of the nasolabial complex using 3D motion capture:
A normative data set.
AB - INTRODUCTION: Smile reanimation should be considered from a dynamic perspective.
Any intervention should restore normality. To date no such normative dynamic data
has been published. AIM: To quantitatively analyse maximal smiles between a
healthy group of Caucasian male and female adults using 3D motion capture (4D
stereophotogrammetry). METHOD: Using a 3D facial motion capture system 54 males
and 54 female volunteers were imaged whilst performing a maximal smile. Eight
nasolabial landmarks were digitised and tracked. Differences in displacement and
speed of bilateral landmarks between males and females were analysed in each
direction (x, y, z and Euclidian), from rest (T0), to median smile (T1) and
maximal smile (T2), using paired t-tests and Wilcoxon-Signed Rank tests. RESULTS:
In males and females the displacement and speed of the left and right alar base
landmarks were similar in the x and y directions but less in the z direction. For
the philtrum, the displacement and speed of the bilateral landmarks were similar
in the y and z directions, but less in the x direction. The left alar base and
left philtrum moved significantly more in males. Left and right cheilion moved a
similar amount in the x and y directions but more in the z direction. Labiale
superius moved significantly more in the z direction, and labiale inferius moved
significantly more in the y direction in males. In conclusion, this study has
presented a novel normative data set of dynamic nasolabial complex movement for
males and females during maximum smile. The data, as well as providing magnitudes
of displacements of the nasolabial complex, also provides the speeds of movement.
PMID- 29958845
TI - Newborn screening for congenital adrenal hyperplasia: beyond 17
hydroxyprogesterone concentrations.
PMID- 29958844
TI - Acquired neuromuscular dysfunction in the intensive care unit.
AB - INTRODUCTION: Polyneuropathy and myopathy, grouped under the term "intensive care
unit-acquired weakness" (ICUAW), are neuromuscular pathologies to which patients
in the intensive care unit (ICU) are susceptible. They are multifactorial
pathologies, prolonged connection to a ventilator is one of the most common. The
objective of this review was to identify the efficacy of different rehabilitative
treatments in patients with ICUAW, and the relationship between ICUAW and a
series of indicators. METHODS: A systematic review of the primary studies
selected from the Medline, Scielo, Web of Science, Cochrane, Cuiden and Science
Direct databases was carried out, following the guidelines of the PRISMA
statement, by which the search protocol was established. RESULTS AND CONCLUSIONS:
Of 161 articles, only 10 were selected to be part of this review, in which a
total of 717 patients admitted to the ICU were studied. A statistically
significant relationship was observed between ICUAW and failure in ventilator
disconnection, mortality, increase in ICU stay and the time that the patients
required mechanical ventilation. Moreover, all this improved in this type of
patients with the application of a rehabilitation therapy. The use of
corticosteroids, was not shown to be related to neuromuscular alteration.
PMID- 29958846
TI - Partially 13C-labeled mouse tissue as reference for LC-MS based untargeted
metabolomics.
AB - The inclusion of stable isotope-labeled reference standards in the sample is an
established method for the detection and relative quantification of metabolic
features in untargeted metabolomics. In order to quantify as many metabolites as
possible, the reference should ideally include the same metabolites in their
stable isotope-labeled form as the sample under investigation. We present here an
attempt to use partially 13C-labeled mouse material as internal standard for
relative metabolite quantification of mouse and human samples in untargeted
metabolomics. We fed mice for 14 days with a13C-labeled Ralstonia eutropha based
diet. Tissue and blood amino acids from these mice showed 13C enrichment levels
that ranged from 6% to 75%. We used MetExtract II software to automatically
detect native and labeled peak pairs in an untargeted manner. In a dilution
series and with the implementation of a correction factor, partially 13C-labeled
mouse plasma resulted in accurate relative quantification of human plasma amino
acids using liquid chromatography coupled to mass spectrometry, The coefficient
of variation for the relative quantification is reduced from 27% without internal
standard to 10% with inclusion of partially 13C-labeled internal standard. We
anticipate the method to be of general use for the relative metabolite
quantification of human specimens.
PMID- 29958847
TI - Radiomic biomarkers informative of cancerous transformation in neurofibromatosis
1 plexiform tumors.
AB - BACKGROUND: This study explores whether objective, quantitative radiomic
biomarkers derived from magnetic resonance (MR), positron emission tomography
(PET), and computed tomography (CT) may be useful in reliably distinguishing
malignant peripheral nerve sheath tumors (MPNST) from benign plexiform
neurofibromas (PN). METHODS: A registration and segmentation pipeline was
established using a cohort of NF1 patients with histopathological diagnosis of PN
or MPNST, and medical imaging of the PN including MR and PET-CT. The corrected MR
datasets were registered to the corresponding PET-CT via landmark-based
registration. PET standard-uptake value (SUV) thresholds were used to guide
segmentation of volumes of interest: MPNST-associated PET-hot regions (SUV>=3.5)
and PN-associated PET-elevated regions (2.033% or an absolute increase >6 mL on
follow-up CT scans), and performed a logistic regression analysis to determine
the predictors of HE. RESULTS: A total of 118 patients (78 men; median age 63
years; interquartile range 54-73) were included in our study. HE was observed in
30 patients (25%). HE patients showed higher rates of anticoagulant use (20% vs.
2%, respectively; P=0.003), high National Institutes of Health Stroke Scale on
admission (13 vs. 7, respectively; P=0.001), and high plasma glucose (141 mg/dl
vs. 113 mg/dl, respectively; P=0.001) compared with patients without HE. After
multivariate logistic regression analysis, we selected three factors for defining
the NAG scale (1 point as baseline National Institutes of Health Stroke Scale
>=10, 1 point as anticoagulant use, and 1 point as plasma glucose >=133 mg/dL).
The frequencies of HE associated with the NAG scale scores were as follows: score
0, 4%; score 1, 25%; score 2, 60%; score 3, 100%. CONCLUSION: Stroke severity,
hyperglycemia, and anticoagulation use were factors independently associated with
HE. The NAG scale consists of readily available factors and can predict HE.
PMID- 29958848
TI - Endovascular Treatment of Acute Basilar Artery Occlusion: Registro Endovascolare
Lombardo Occlusione Basilar Artery (RELOBA) Study Group Experience.
AB - BACKGROUND: Acute basilar artery occlusion (BAO) is considered among the most
severe medical emergencies, with very high morbidity and mortality. The aims of
this study are to present 5 years experience of 12 centers in Lombardy region on
BAO endovascular treatment and to evaluate prognostic factors that may improve
clinical outcomes and recanalization rates. MATERIALS AND METHODS: Registro
Endovascolare Lombardo Occlusione Basilar Artery (RELOBA) registry is a
retrospective multicentric collection of patients with acute BAO who underwent
endovascular treatment between 2010 and 2015. A total of 102 patients (mean age
65 years) were included. Clinical, procedural, and neuroradiological data were
collected. Angiographic results (Treatment in Cerebral Ischemia scale [TICI]
score 2b-3) were assessed by each center's interventional neuroradiologist. Good
clinical outcome was considered as a modified Rankin Scale score ranging between
0 and 2 in a 3-month follow-up. RESULTS: Thirty-nine percent of patients showed
good clinical outcome at 3 months. Mortality rate was 30%. TICI 2b-3 was achieved
in 62% of patients. Univariate analysis showed that age, National Institutes of
Health Stroke Scale (NIHSS) at onset, time to recanalization, and TICI score were
all statistically significant clinical outcome predictors (P < .05). Multivariate
logistic regression showed that time to recanalization, age, and NIHSS at onset
were significant independent predictors of good outcome. CONCLUSIONS: BAO
treatment needs more efforts to assure patients better clinical outcomes.
Mechanical thrombectomy is feasible and effective in patients with acute BAO.
These results must be confirmed by further prospective studies within randomized
controlled settings.
PMID- 29958850
TI - Postnatal changes in epigenetic modifications of neutrophils of foals are
associated with increased ROS function and regulation of neutrophil function.
AB - Neonates of all species, including foals, are highly susceptible to infection,
and neutrophils play a crucial role in innate immunity to infection. Evidence
exists that neutrophils of neonatal foals are functionally deficient during the
first weeks of life, including expression of cytokine genes such as IFNG. We
hypothesized that postnatal epigenetic changes were likely to regulate the
observed age-related changes in foal neutrophils. Using ChIP-Seq, we identified
significant differences in trimethylated histone H3 lysine 4, an epigenetic
modification associated with active promoters and enhancers, in neutrophils in
foals at 30 days of age relative to 1 day of age. These chromatin changes were
associated with genes implicated in immune responses and were consistent with age
related changes in neutrophil functional responses including ROS generation and
IFN expression. Postnatal changes in epigenetic modifications suggest that
environmentally-mediated cues help to promote maturation of neutrophil functional
responses. Elucidating the environmental triggers and their signaling pathways
could provide a means for improving innate immune responses of neonates to
improve their ability to combat infectious diseases.
PMID- 29958851
TI - One in three: challenging heteronormative assumptions in family planning health
centers.
AB - OBJECTIVES: To estimate the prevalence of sexual-minority women among clients in
family planning centers and explore differences in LARC uptake by both sexual
identity (i.e., exclusively heterosexual, mostly heterosexual, bisexual, lesbian)
and sexual behavior in the past 12 months (i.e., only male partners, both male
and female partners, only female partners, no partners) among those enrolled in
the survey arm of the HER Salt Lake Contraceptive Initiative. METHODS: This
survey categorized participants into groups based on reports of sexual identity
and sexual behavior. We report contraceptive uptake by these factors, and we used
logistic and multinomial logistic models to assess differences in contraceptive
method selection by sexual identity and behavior. RESULTS: Among 3901 survey
respondents, 32% (n=1230) identified with a sexual-minority identity and 6% had
had a female partner in the past 12 months. By identity, bisexual and mostly
heterosexual women selected an IUD or implant more frequently than exclusively
heterosexual women and demonstrated a preference for the copper T380 IUD.
Exclusively heterosexual and lesbian women did not differ in their contraceptive
method selection, however, by behavior, women with only female partners selected
IUDs or implants less frequently than those with only male partners. CONCLUSION:
One in three women attending family planning centers for contraception identified
as a sexual minority. Sexual-minority women selected IUDs or implants more
frequently than exclusively heterosexual women. IMPLICATIONS: Providers should
avoid care assumptions based upon sexual identity. Sexual-minority women should
be offered all methods of contraception and be provided with inclusive
contraceptive counseling conversations.
PMID- 29958852
TI - Capturing compassion: A survey of Mexican Catholics assessing abortion support by
reason for abortion and degree of Catholicism.
AB - OBJECTIVE: No standard exists to measure religiosity in abortion studies. We test
whether religiosity is associated with support for abortion among Mexican
Catholics and whether different measures of degree of Catholicism alter the
relationship. STUDY DESIGN: We conducted a nationally representative cross
sectional study using survey data from 2669 self-identified Mexican Catholics
(response rate 85%). Our three outcomes were 1) overall support for legal
abortion and support for abortion under exceptions, grouped as having 2)
traditionally high agreement (rape, life) and 3) low agreement (on demand,
socioeconomic). We used logistic regression controlling for sociodemographic
covariates to test the association of four measures of Catholicism with our
outcomes. RESULTS: The majority of Mexican Catholics support abortion in some
circumstances. (90% at least one high agreement exception and 40% at least one
low agreement exception). The only measure of degree of Catholicism significantly
associated with all our outcomes was belief that a person who helps someone who
aborts can be a good Catholic. Those who agreed (versus not) had higher odds of
support for abortion for both high agreement (aOR 3.6 [95% CI: 1.7-7.9]) and low
agreement (aOR 1.9 [95% CI: 1.3-2.7]) exceptions. Respondents who believe a woman
who aborts does not need to confess (aOR 2.1 [95% CI: 1.5-2.8]) or needs to
confess to God (aOR 1.4 [95% CI: 1.04-1.8]) versus a priest had higher odds of
agreement with at least one low agreement exception. CONCLUSION: Opinion toward
abortion among Mexican Catholics is diverse. More nuanced measures of Catholicism
are valuable in assessing support for abortion, especially exceptions with low
support. IMPLICATIONS: The main reasons women need abortion are precisely those
with low support among Mexican Catholics. Focusing on nuanced measures of
Catholicism can help us identify areas for shared values and frame messaging to
meet the diversity of Catholic opinion. Catholicism is not an unsurmountable
barrier to liberalization of abortion law.
PMID- 29958853
TI - HIV treatment in pregnancy.
AB - Almost 25 years since antiretroviral therapy (ART) was first shown to prevent
mother-to-child transmission of HIV, 76% of pregnant women living with HIV (over
1 million women) receive ART annually. This number is the result of successes in
universal ART scale-up in low-income and middle-income countries. Despite
unprecedented ART-related benefits to maternal and child health, challenges
remain related to ART adherence, retention in care, and unequal access to ART.
Implementation research is ongoing to understand and to address obstacles that
lead to loss to follow-up. The biological mechanisms that underlie observed
associations between antenatal ART and adverse outcomes in pregnancy and birth
are not completely understood, with further research needed as well as
strengthening of the systems to assess safety of antiretroviral drugs for the
mother and HIV-exposed child. In the treat-all era, as duration of treatment and
options for ART expand, pregnant women will remain a priority population for
treatment optimisation to promote their health and that of their ART-exposed
children.
PMID- 29958854
TI - Understanding and Assessing Nontechnical Skills in Robotic Urological Surgery: A
Systematic Review and Synthesis of the Validity Evidence.
AB - OBJECTIVE: Robotic urological surgery (RUS) has seen widespread adoption across
institutions in the last decade. To match this rapid growth, it is imperative to
develop a structured RUS curriculum that addresses both technical and
nontechnical competencies. Emerging evidence has shown that nontechnical skills
form a critical component of RUS training. The purpose of this review is to
examine the validity evidence of available nontechnical skills assessment tools
in RUS. METHODS: A literature search of MEDLINE, EMBASE, and PsycINFO was
conducted to identify primary articles using nontechnical skills assessment tools
in RUS. Messick's validity framework and the Medical Education Research Study
Quality Instrument were utilized to evaluate the quality of the validity evidence
of the abstracted articles. RESULTS: Of the 566 articles identified, 12 used
nontechnical skills assessment tools in RUS. The metrics used ranged from self
assessment using global rating scales, to objective measures such as
electroencephalography. The setting of these evaluations ranged from immersive
and virtual reality-based simulators to live surgery. CONCLUSIONS: Limited effort
has been made to develop nontechnical skills assessment tools in RUS. Recently,
there has been a shift from subjective to objective measures of nontechnical
performance, as well asthe development of assessments specific to RUS. However,
the validity evidence supporting these nontechnical assessments is limited at
this time, including their relationship to technical skills, and their impact on
surgical outcomes.
PMID- 29958855
TI - Efficacy of Sofosbuvir and Velpatasvir, With and Without Ribavirin, in Patients
With Hepatitis C Virus Genotype 3 Infection and Cirrhosis.
AB - BACKGROUND & AIMS: In phase 3 trials and real-world settings, smaller proportions
of patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have
a sustained virologic response 12 weeks after treatment (SVR12) with the
combination of sofosbuvir and velpatasvir than in patients without cirrhosis. It
is unclear whether adding ribavirin to this treatment regimen increases SVRs in
patients with genotype 3 HCV infection and cirrhosis. METHODS: We performed a
phase 2 trial of 204 patients with genotype 3 HCV infection and compensated
cirrhosis (mean age 51 +/- 7.4 years) at 29 sites in Spain from August 19, 2016
through April 18, 2017. Patients were assigned to groups given sofosbuvir and
velpatasvir for 12 weeks (n = 101) or sofosbuvir and velpatasvir plus ribavirin
for 12 weeks (n = 103). The primary efficacy end point was SVR12. RESULTS: The
overall rates of SVR12 were 91% (92 of 101; 95% CI 84-96) for the sofosbuvir
velpatasvir group and 96% (99 of 103; 95% CI 90-99) for the sofosbuvir
velpatasvir plus ribavirin group. In the sofosbuvir-velpatasvir group, a smaller
proportion of patients with baseline resistance-associated substitutions (RASs)
in nonstructural protein 5A (NS5A) achieved an SVR12 (84%) than did patients
without (96%). In the sofosbuvir-velpatasvir plus ribavirin group, baseline RASs
had less effect on the proportion of patients with an SVR12 (96% for patients
with baseline RASs; 99% for patients without). The most common adverse events
(which occurred in >=10% of patients) were asthenia (12%) in the sofosbuvir
velpatasvir group and asthenia (27%), headache (24%), and insomnia (12%) in the
sofosbuvir-velpatasvir plus ribavirin group. CONCLUSIONS: Consistent with
findings from previous studies, a high rate of patients (91% and 96%) with
genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with
sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with
sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A
RASs achieved an SVR12 compared with patients without baseline NS5A.
ClinicalTrials.govNCT02781558.
PMID- 29958856
TI - World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post
Imaging Colorectal Cancer.
AB - BACKGROUND & AIMS: Colonoscopy examination does not always detect colorectal
cancer (CRC)- some patients develop CRC after negative findings from an
examination. When this occurs before the next recommended examination, it is
called interval cancer. From a colonoscopy quality assurance perspective, that
term is too restrictive, so the term post-colonoscopy colorectal cancer (PCCRC)
was created in 2010. However, PCCRC definitions and methods for calculating rates
vary among studies, making it impossible to compare results. We aimed to
standardize the terminology, identification, analysis, and reporting of PCCRCs
and CRCs detected after other whole-colon imaging evaluations (post-imaging
colorectal cancers [PICRCs]). METHODS: A 20-member international team of
gastroenterologists, pathologists, and epidemiologists; a radiologist; and a non
medical professional met to formulate a series of recommendations, standardize
definitions and categories (to align with interval cancer terminology), develop
an algorithm to determine most-plausible etiologies, and develop standardized
methodology to calculate rates of PCCRC and PICRC. The team followed the
Appraisal of Guidelines for Research and Evaluation II tool. A literature review
provided 401 articles to support proposed statements; evidence was rated using
the GRADE (Grading of Recommendations Assessment, Development and Evaluation)
system. The statements were voted on anonymously by team members, using a
modified Delphi approach. RESULTS: The team produced 21 statements that provide
comprehensive guidance on PCCRCs and PICRCs. The statements present standardized
definitions and terms, as well as methods for qualitative review, determination
of etiology, calculation of PCCRC rates, and non-colonoscopic imaging of the
colon. CONCLUSIONS: A 20-member international team has provided standardized
methods for analysis of etiologies of PCCRCs and PICRCs and defines its use as a
quality indicator. The team provides recommendations for clinicians,
organizations, researchers, policy makers, and patients.
PMID- 29958858
TI - Bioavailability of bound microcystins in mice orally fed with contaminated
tilapia edible tissues: Implications to human health.
AB - This study investigates for the first time in vivo potential release of bound
microcystins (MCs) from edible fish tissues. Bound MCs were released in the mouse
digestive system and reached the liver (2.1-14.3 ng g-1) and blood (1-5 ng ml-1).
The released MCs were active and negatively affected liver functions of treated
mice. The estimated daily intake (EDI) for bound MCs (93.5 MUg kg-1 day-1) is
about 2300 times higher than the WHO safe EDI (0.04 MUg kg-1 day-1), compared to
lower EDI for free MCs (0.002 MUg kg-1 day-1). Therefore, bound MCs in fish
tissues should be considered when fish are monitored for human consumption.
PMID- 29958857
TI - Sex-Based Differences in Incidence of Inflammatory Bowel Diseases-Pooled Analysis
of Population-Based Studies From Western Countries.
AB - BACKGROUND & AIMS: Although the incidence of inflammatory bowel diseases (IBDs)
varies with age, few studies have examined variations between the sexes. We
therefore used population data from established cohorts to analyze sex
differences in IBD incidence according to age at diagnosis. METHODS: We
identified population-based cohorts of patients with IBD for which incidence and
age data were available (17 distinct cohorts from 16 regions of Europe, North
America, Australia, and New Zealand). We collected data through December 2016 on
95,605 incident cases of Crohn's disease (CD) (42,831 male and 52,774 female) and
112,004 incident cases of ulcerative colitis (UC) (61,672 male and 50,332
female). We pooled incidence rate ratios of CD and UC for the combined cohort and
compared differences according to sex using random effects meta-analysis.
RESULTS: Female patients had a lower risk of CD during childhood, until the age
range of 10-14 years (incidence rate ratio, 0.70; 95% CI, 0.53-0.93), but they
had a higher risk of CD thereafter, which was statistically significant for the
age groups of 25-29 years and older than 35 years. The incidence of UC did not
differ significantly for female vs male patients (except for the age group of 5-9
years) until age 45 years; thereafter, men had a significantly higher incidence
of ulcerative colitis than women. CONCLUSIONS: In a pooled analysis of population
based studies, we found age at IBD onset to vary with sex. Further studies are
needed to investigate mechanisms of sex differences in IBD incidence.
PMID- 29958859
TI - Pharmacological (ethanol) and mutation (sam2 KO) induced impairment of novelty
preference in zebrafish quantified using a new three-chamber social choice task.
AB - Social behavior is a fundamental aspect of our own species, a feature without
which our society would not function. There are numerous human brain disorders
associated with abnormal social behavior, among them are the autism spectrum
disorders whose causal factors include a genetic component. Environmental
factors, including drugs of abuse such as alcohol, also contribute to numerous
abnormalities related to social behavior. Several such disorders have been
modeled using laboratory animals. Perhaps one of the newest among them is the
zebrafish. However, the paucity of standardized behavioral assays specifically
developed for the zebrafish have hindered progress. Here, we present a newly
developed zebrafish behavioral paradigm, the three-chamber social choice task.
This task, which was adapted from a murine model, assesses sociality and social
novelty preference in zebrafish in three phases: habituation, phase-I to evaluate
sociality, and phase-II to quantify social novelty preference. Test fish are
placed in the middle chamber, while conspecifics are introduced to the flanking
chambers during phase-I and II. Both male and female zebrafish displayed
sociality (preference for conspecifics) during phase-I and social novelty
preference (preference for unfamiliar conspecifics) during phase-II. We found the
paradigm to be able to detect both environmentally (alcohol) as well as
genetically (targeted knock out of sam2) induced alterations of behavioral
phenotypes. Although ethanol-treated fish displayed similar levels of sociality
to those of control (not alcohol exposed) male and female zebrafish, they were
found to exhibit significantly impaired social novelty preference, a finding
compatible with altered motivational or perhaps mnemonic processes. Moreover, we
found that knock out of sam2, previously shown to lead to emotional
dysregulation, also disrupted social novelty preference, while leaving sociality
relatively intact. We conclude that our novel behavioral paradigm is appropriate
for the modeling and quantification of social behavior deficits in zebrafish.
PMID- 29958860
TI - Acceptability of self-sampling and human papillomavirus testing among non
attenders of cervical cancer screening programs in El Salvador.
AB - In a cross-sectional study carried out in El Salvador between February 2016 and
July 2017, self-sampling and human papillomavirus (HPV) testing was found to be
highly acceptable among 2019 women who had not attended a cervical cancer
screening in at least 3 years. Within this population, HPV positivity rates
differed according to age, marital status, number of children, and lifetime
sexual partners. The proportion of women who tested HPV positive or who were
diagnosed with cervical intraepithelial neoplasia grade 2 (CIN2) or more severe
diagnoses (CIN2+) was similar to the general population of the area. Among the
reasons for failing to participate in previous screening programs, non-attending
women described logistic concerns, but also erroneous beliefs regarding HPV and
cervical cancer, misconceptions regarding the screening procedure, discomfort
with male providers, and confidentiality fears. The aim of this study was to
identify opportunities and challenges that emerged from the use of self-sampling
and HPV testing as part of a public cervical cancer control effort in a low
resource setting.
PMID- 29958861
TI - Nicotine and addiction beliefs and perceptions among the US-born and foreign-born
populations.
AB - Little is known about nicotine and addiction beliefs held by those who are
foreign-born in the US and how these beliefs are associated with acculturation
and race/ethnicity. This study attempts to address these research gaps. Data were
analyzed from two cycles of the Health Information National Trends Survey, HINTS
FDA 2015 (n = 3738) and HINTS-FDA 2017 (n = 1736). HINTS-FDA is a tobacco
focused, cross-sectional, nationally representative survey of US non
institutionalized civilian adults aged 18 years or older. We first assessed
associations between foreign-born status and beliefs about nicotine and addiction
using weighted chi-square analyses. Then, using only the foreign-born sample, we
examined the associations of nicotine and addiction beliefs with race/ethnicity
and acculturation (i.e., English proficiency and U.S. tenure) using weighted
multiple linear regression. Results showed that, compared to US-born respondents,
foreign-born respondents were more likely to be concerned with being addicted to
nicotine and to believe that low nicotine cigarettes would have much lower lung
cancer risk than a typical cigarette. Among the foreign-born, NH-Black and
Hispanic respondents were more likely to see low nicotine cigarettes as harmful
and addictive compared to NH-White respondents. The relationship between
acculturation and nicotine beliefs was complex with lower acculturation
associated with elevated misperceived risk of nicotine and also ratings of
addictiveness. Further research among key subpopulations may inform
communication, education and dissemination strategies, especially among
vulnerable populations.
PMID- 29958862
TI - Microvascular endothelial dysfunction during cardiopulmonary bypass in surgery
for correction of cyanotic and acyanotic congenital heart disease.
AB - OBJECTIVE: To evaluate endothelium-dependent microvascular reactivity during
cardiopulmonary bypass (CPB) in surgery for the correction of cyanotic and
acyanotic congenital heart disease (CHD) in children and infants using laser
Doppler perfusion monitoring (LDPM). METHODS: This cross-sectional observational
study included one hundred consecutive acyanotic (AC, n = 61) and cyanotic (C, n
= 39) pediatric patients scheduled for cardiac surgery for correction of CHD. The
endothelium-dependent microvascular vasodilation of the skin of the forehead was
evaluated using a single-point LDPM coupled with local thermal hyperemia (LTH).
RESULTS: LTH induced significant increases in microvascular conductance both in
AC and C patients after the induction of anesthesia, during CPB and after weaning
from CPB. Nevertheless, the vasodilation induced by LTH was significantly blunted
during CPB when compared with values obtained after the induction of anesthesia
both in AC and C patients. Microvascular endothelial reactivity nearly normalized
after the discontinuation of CPB. CONCLUSION: The evaluation of systemic
microvascular reactivity on the forehead skin of infants and children using LDPM
appears to be a valuable tool for optimizing microvascular perfusion during CPB
in pediatric cardiac surgery.
PMID- 29958863
TI - Image enhancement effect on inter and intra-observer reliability of nailfold
capillary assessment.
AB - BACKGROUND: Nailfold capillaroscopy (NC) is a diagnostic imaging technique that
is used to assess the blood capillary network in the nailfold area. NC is
routinely used for patients with microcirculation problems, such as systemic
sclerosis and other connective tissue diseases. Experts commonly use subjective
evaluation as a reference point in images of nailfold video capillaroscopy, so it
is important to reduce the inherent ambiguities in human judgment and diagnosis.
Image quality is an important factor that affects measurement error and
assessment time of NC images. OBJECTIVE: In this study, a new image enhancement
technique was introduced and evaluated subjectively. METHODS: In total, 475
nailfold video capillaroscopy images from 18 healthy subjects and 41 systemic
lupus erythematosus patients were used. The images were randomly divided into two
sets, one each with 275 and 200. Eight independent observers who were familiar
with the capillaroscopy technique participated in this study. The set of 275
images was evaluated by three observers with the forced-choice pairwise
comparison method. Elliptic broken line (EBL) was used to count the number of
capillaries. The intra- and inter-observer reliability of the original and
enhanced images was evaluated on 200 images by five observers. RESULT: Except for
eight images, all observers preferred the enhanced images in the visual quality
comparison method. The intra-class correlation coefficient (ICC) of intra- and
inter-observer reliability increased from 0.76-0.84 to 0.82-0.89, respectively,
when using the enhancement method. CONCLUSION: By improving the image quality,
more capillary details will be visible, and an observer can document more details
that may not be visible in the original image and can do so more efficiently.
PMID- 29958864
TI - Improving prediction of eating-related behavioral outcomes with zero-sensitive
regression models.
AB - OBJECTIVE: Outcome variables gauging the frequency of specific disordered eating
behaviors (e.g., binge eating, vomiting) are common in the study of eating and
health behaviors. The nature of such data presents several analytical challenges,
which may be best addressed through the application of underutilized statistical
approaches. While zero-sensitive models are well-supported by methodologists,
application of these models has yet to gain traction among a widespread audience
of researchers who study eating-related behaviors. The current study examined
several approaches to predicting count-based behaviors, including zero-sensitive
(i.e., zero-inflated and hurdle) regression models. METHOD: Exploration of
alternative models to predict eating-related behaviors occurred in two parts. In
Part 1, participants (N = 524; 54% female) completed the Eating Disorder
Examination-Questionnaire and Daily Stress Inventory. We considered the
theoretical basis and practical utility of several alternative approaches for
predicting the frequency of binge eating and compensatory behaviors, including
ordinary least squares (OLS), logistic, Poisson, negative binomial, and zero
sensitive models. In Part 2, we completed Monte Carlo simulations comparing
negative binomial, zero-inflated negative binomial, and negative binomial hurdle
models to further explore when these models are most useful. RESULTS: Traditional
OLS regression models were generally a poor fit for the data structure. Zero
sensitive models, which are not limited to traditional distribution assumptions,
were preferable for predicting count-based outcomes. In the data presented, zero
sensitive models were useful in modeling behaviors that were relatively rare
(laxative use and vomiting, 9.7% endorsed) along with those that were somewhat
common (binge eating, 33.4% endorsed; driven exercise, 40.7% endorsed).
Simulations indicated missing data, sample size, and the number of zeros may
impact model fit. DISCUSSION: Zero-sensitive approaches hold promise for
answering key questions about the presence and frequency of common eating-related
behaviors and improving the specificity of relevant statistical models. The
current manuscript provides practical guidance to aid the use of these models
when studying eating-related behaviors.
PMID- 29958865
TI - Increasing Use of Intensive Care Unit for Odontogenic Infection Over One Decade:
Incidence and Predictors.
AB - PURPOSE: To determine whether intensive care unit (ICU) admissions for
odontogenic infections have increased during the past decade and whether certain
clinical features are associated with a greater rate of ICU admission. MATERIALS
AND METHODS: The data from patients undergoing surgery for odontogenic infections
at the Royal Brisbane and Women's Hospital in the 24 month from January 2003 to
December 2004 were compared with those from patients treated from January 2013 to
December 2014. A chi2 analysis was used to compare the demographic, admission,
and clinical patient data in each cohort. A multiple logistic regression model
was used to determine which clinical features were associated with greater rates
of ICU admission. RESULTS: The rate of ICU admission increased significantly from
7 to 24% during the decade (chi2 = 12.74; P = .000), although the clinical
presentation of patients admitted to the ICU was similar in both cohorts. The
mean number of days spent in the ICU increased significantly from 1.7 +/- 0.5 to
3.24 +/- 2.5 days (t = -3.63; P = .001), and the overall length of stay increased
from 1.7 +/- 0.5 to 3.5 +/- 4.1 days (t = 2.99; P = .004). The use of
preoperative computed tomography (CT) increased significantly from 42.9 to 93.3%
(chi2 = 13.25; P = .000). The most significant predictors of ICU admission were
lower third molar involvement (P = .026), dysphagia (P = .020), and C-reactive
protein (CRP) levels exceeding 150 mg/L (P = .039). CONCLUSIONS: The use of the
ICU in the management of odontogenic infection has increased significantly at the
Royal Brisbane and Women's Hospital over 1 decade. The demographic data and
clinical presentation of the patients admitted to the ICU did not change
significantly. However, the length of ICU stay and the total length of stay have
both increased. A significant increase in CT usage for odontogenic infections
also occurred. Third molar infections, dysphagia, and elevated CRP might be
relevant clinical predictors of a more complicated course of care requiring ICU
admission. More judicious use of CT scanning, combined with prompt surgical
consultation and intervention, might reduce the rate of ICU admissions for
odontogenic infections.
PMID- 29958866
TI - Severe community-acquired pneumonia due to Pseudomonas aeruginosa coinfection in
an influenza A(H1N1)pdm09 patient.
AB - Coinfection with Pseudomonas aeruginosa in patients with influenza is rare.
Herein, we report a 39-year-old female patient who presented with severe
community-acquired pneumonia due to coinfection with influenza A(H1N1)pdm09 and
P. aeruginosa, which progressed to multifocal pneumonia with a fatal outcome.
PMID- 29958867
TI - Rapid B1 field mapping at 3 T using the 180 degrees signal null method with
extended flip angle.
AB - PURPOSE: To extend the null signal method (NSM) for B1 mapping to 3 T magnetic
resonance imaging (MRI). BACKGROUND: The NSM operates in the steady state regime
and exploits the linearity of the spoiled gradient recalled echo (SPGR) signal
around the 180 degrees flip angle (FA). Using linear regression, B1 maps are
derived from three SPGR images acquired at different FAs with a short repetition
time. While the conventional NSM allows accurate mapping of B1 for moderate B1
variation, we observed that this method fails for the larger B1 variations
typical of high-field MRI. METHODS: We analyzed the effect of the FA range of the
acquired SPGR images on B1 determination using the NSM for 3 T MRI through
extensive numerical and in vivo analyses. B1 maps derived from the extended angle
range NSM (EA-NSM) were calculated and compared to those derived from the
conventional, more restricted angle range, NSM, and to those derived from the
reference, but much more time-consuming, double angle method (DAM). Furthermore,
we investigated the compatibility of EA-NSM B1 mapping and the half-scan and
SENSE reconstruction methods for accelerating acquisition time. RESULTS: Our
results show that the use of the conventional FA range leads to substantial
inaccuracies in B1 determination. Both numerical and in vivo analyses demonstrate
that expanding the FA range of the acquired SPGR images substantially improves
the accuracy of B1 maps. Furthermore, B1 maps derived from EA-NSM were
demonstrated to be quantitatively comparable to those derived from the lengthy
DAM protocol. We also found that B1 maps derived from SPGR images using the EA
NSM and imaging acceleration methods were comparable to those derived from images
acquired without acceleration. Finally, the use of half scanning combined with
SENSE reconstruction permits whole-brain B1 mapping in ~1 min. CONCLUSIONS: The
EA-NSM permits accurate, fast, and practical B1 mapping in a 3 T clinical
setting.
PMID- 29958868
TI - Evaluating the effects of receive-only arrays in specific absorption rate
simulations at 3 and 7 T.
AB - Specific absorption rate (SAR) simulations are performed for most clinical and
research transmit coil configurations. Such simulations allow the determination
of limits in transmit power for patient safety. Different human models and coil
configurations have been previously investigated using these simulations.
However, only a few works have accounted for the effect of the receive (Rx)
arrays in the SAR calculations and they have used very specialized setups or
simplified detuning modeling of the Rx elements. In this work, we performed
electromagnetic simulations using a clinical alike setup for whole-body scans at
3 T and head scans at 7 T. SAR simulations are performed for both setups with and
without Rx arrays. A difference below 10% percent was found for max SAR. The
maximum difference for the mean SAR values of the 3 T setups remained within 8%
and within 15% of the 7 T setup.
PMID- 29958869
TI - Essential function of NHE8 in mouse retina demonstrated by AAV-mediated
CRISPR/Cas9 knockdown.
AB - We studied the role of sodium/proton exchanger 8 (NHE8) in retinal pigment
epithelium (RPE) and photoreceptor cells of adult mouse retina by using the
clustered regularly interspaced short palindromic repeats (CRISPR)-associated
endonuclease (Cas)9 from Neisseria meningitidis (Nm). Specific single guide RNAs
(sgRNAs) were designed to knockdown the Slc9a8 gene, which encodes the NHE8.
Nuclease null NmCas9 and sgRNAs were packaged respectively using adeno-associated
viral vector (AAV), and delivered into mouse eyes in vivo by subretinal injection
on wild-type mice of about four-week-old when mouse retina is fully developed.
Eye samples were collected four weeks after injection for phenotype examination.
Real-time PCR analysis demonstrated ~38% reduction of NHE8 transcripts in retinas
injected with AAV-knockdown sgRNA and AAV-Cas9. Loss of photoreceptor cells was
found in eyes injected with AAV-knockdown sgRNA and AAV-Cas9 under either the
human rhodopsin promoter or the minimal chicken beta-actin promoter, while normal
morphology was observed in control eyes injected with AAV-Cas9 and AAV-control
sgRNA; immunostaining data showed degenerating photoreceptor cells and RPE cells
in eyes injected with knockdown sgRNA and Cas9 AAVs. We further determined that
mutant M120K-NHE8 displayed altered intracellular pH regulation in human RPE and
primary mouse RPE cells using genetically encoded pH sensor pHluorin and that
primary cultured NHE8 mutant RPE cells showed different pH titration curves.
These results indicate that NHE8 plays essential function in both RPE and
photoreceptor cells. NHE8 dysfunction either in photoreceptor or RPE is
sufficient to cause retinal degeneration in adult mice at any age.
PMID- 29958871
TI - Basic fibroblast growth factor increased glucocorticoid receptors in cortical
neurons through MAP kinase pathway.
AB - Prolonged and intense stress chronically increases blood concentration of
glucocorticoids, which in turn causes downregulation of glucocorticoid receptor
(GR) in the central nervous system (CNS). This process has been suggested to be
involved in the pathogenesis of major depressive disorder (MDD). Here, we found
that basic fibroblast growth factor (bFGF) increased the expression of GR in the
rat cerebral cortex and cultured cortical neurons and restored the reduced GR
expression caused by glucocorticoid exposure. Among intracellular signaling
pathways stimulated by bFGF, extracellular signal-regulated kinase/mitogen
activated protein kinase (ERK/MAPK) pathway was responsible for the upregulation
of GR. The bFGF-induced GR was functional as a transcription factor to enhance
transcription of a target gene. Because high stress augments bFGF levels in the
brain, it is likely that bFGF plays a compensating role for reduced GR expression
after stress and thus should be studied as a therapeutic target for the treatment
of MDD.
PMID- 29958870
TI - Effects of silver sulfide quantum dots coated with 2-mercaptopropionic acid on
genotoxic and apoptotic pathways in vitro.
AB - Quantum dots (QDs) are highly promising nanomaterials in bioimaging system
because of their bright fluorescence, broad UV excitation, narrow emission band,
and high photostability. Recently, there is a great activity on Ag2S quantum dots
for both imaging and drug/gene delivery due to the potential of having a better
cytocompatability and near infrared luminescence. 2-Mercaptopropionic acid (2 MP
A)-coated silver sulfide (Ag2S) QDs were reported as the most luminescent,
stable, anionic Ag2S QDs in the literature. In this study, we aim to determine
the cytotoxicity of 2 MP A/Ag2S in Chinese hamster lung fibroblast (V79) cells.
The genotoxic and apoptotic effects of 2 MP A/Ag2S QDs were assessed by the
alkaline single cell electrophoresis assay and real time polymerase chain
reaction techniques, respectively. The cell viability decreased above 200 MUg/ml
and 800 MUg/ml for MTT tetrazolium and neural red uptake assays, respectively.
DNA damage was not observed by 2 MP A/Ag2S QDs at the studied concentration
levels (5-2000 MUg/ml). The levels of mRNA expression of p53, caspase 3, caspase
9, bax, bcl-2, survivin were not changed by 2 MP A/Ag2S QDs below IC50 (around
1000 MUg/ml). Hence, 2 MP A/Ag2S QDs did not show any cytotoxic or genotoxic
effects in V79 cells at lower doses. We conclude that the biocompatibility of 2
MP A/Ag2SODs makes them suitable for cell labeling applications.
PMID- 29958872
TI - The role of the anterior insula in social norm compliance and enforcement:
Evidence from coordinate-based and functional connectivity meta-analyses.
AB - Economic games -trust (TG) and ultimatum game (UG)- combined with fMRI have shown
the importance of the anterior insula (AI) in social normative behaviors.
However, whether different AI subregions are engaged in different cognitive and
affective processes for social norm compliance and norm enforcement during social
exchange remains elusive. Here, we investigated the role of the dorsal AI (dAI)
and ventral AI (vAI), combining a coordinate-based meta-analysis of fMRI studies
using the TG and UG with meta-analytic task-based and task-free connectivity
analyses. Our findings showed that the right dAI and vAI were the only common
brain regions consistently activated across games. These clusters were part of
two functionally distinguishable connectivity networks associated with cognitive
(dAI) and emotional (vAI) processes. In conclusion, we propose that dAI mediates
cognitive processes that generate expectancy for norm compliance, whereas vAI
mediates aversive feelings that generate motivation to norm enforcement. The
identified functional differentiation of the right AI in the social domain
contributes to a better understanding of its role in basic and clinical
neuroscience.
PMID- 29958873
TI - A spatial frequency spectral peakedness model predicts discrimination performance
of regularity in dot patterns.
AB - Subjective assessments of spatial regularity are common in everyday life and also
in science, for example in developmental biology. It has recently been shown that
regularity is an adaptable visual dimension. It was proposed that regularity is
coded via the peakedness of the distribution of neural responses across receptive
field size. Here, we test this proposal for jittered square lattices of dots. We
examine whether discriminability correlates with a simple peakedness measure
across different presentation conditions (dot number, size, and average spacing).
Using a filter-rectify-filter model, we determined responses across scale.
Consistently, two peaks are present: a lower frequency peak corresponding to the
dot spacing of the regular pattern and a higher frequency peak corresponding to
the pattern element (dot). We define the "peakedness" of a particular
presentation condition as the relative heights of these two peaks for a perfectly
regular pattern constructed using the corresponding dot size, number and spacing.
We conducted two psychophysical experiments in which observers judged relative
regularity in a 2-alternative forced-choice task. In the first experiment we used
a single reference pattern of intermediate regularity and, in the second,
Thurstonian scaling of patterns covering the entire range of regularity. In both
experiments discriminability was highly correlated with peakedness for a wide
range of presentation conditions. This supports the hypothesis that regularity is
coded via peakedness of the distribution of responses across scale.
PMID- 29958874
TI - Lag of accommodation does not predict changes in eye growth in chickens.
AB - Emmetropization is controlled by the defocus in the retinal image. It is a
classical problem how changes in focus, introduced by accommodation, are taken
into account. We have quantified accommodation errors in chickens wearing
negative lenses to find out whether they can predict subsequent eye growth. Two
groups of chicks, aged 10 to 13 days, wore lenses (-7D) monocularly for 4-7 days.
Fellow eyes remained untreated. Vitreous chamber depth (VCD) was measured in
alert hand-held chickens with high resolution, using the Lenstar LS 900 (Haag
Streit, Koeniz, Switzerland). Non-cycloplegic refractive state was measured by
automated infrared photoretinoscopy with and without the lenses in place. In
group 1 (n = 6), measurements were done 5 times a day to obtain detailed VCD
growth curves. In group 2 (n = 10), measurements were only taken twice, at 9 am
and 4 pm, to reduce the risk of recovery from induced myopia due to the frequent
removal of the lenses. As expected from the negative power of the lenses,
refractions measured through the lenses were more hyperopic although not as much
as predicted by the lens powers, indicating that chickens partially refocused
their eyes by accommodation. Among different animals, accommodation errors varied
from 1.1 +/- 0.9 to 3.6 +/- 1.1D (group 1, mean +/- 1 standard deviation) and
0.22 +/- 1.25 to 1.72 +/- 1.23D (group 2). No correlations were found between the
magnitude of the accommodation errors in individual animals and subsequent
changes in VCD. With negative lenses, VCD grew both during day and night while
fellow eyes grew only during the day but shrank during the night. In conclusion,
accommodation errors did not predict future eye growth. This raises the question
as to why brief periods of clear vision, when lenses are taken off, have a strong
inhibitory effect on myopia development while periods of clear vision due to
accommodation have apparently no effect. A possible explanation is that, in
addition to retina-driven control of eye growth, there is a second neural pathway
for the control of eye growth that carries the signal of accommodation - although
it is striking that no neuronal and structural correlate has been identified to
date.
PMID- 29958875
TI - The Limits of Cardiac Performance: Can Too Much Exercise Damage the Heart?
AB - Routine moderate-intensity physical activity confers numerous cardiovascular
benefits and reduces all-cause mortality. However, the health impact of exercise
doses that exceed contemporary physical activity guidelines remains incompletely
understood, and an emerging body of literature suggests that high levels of
exercise may have the capacity to damage the cardiovascular system. This review
focuses on the contemporary controversies regarding high-dose exercise and
cardiovascular morbidity and mortality. We discuss the limitations of available
studies, explore potential mechanisms that may mediate exercise-related cardiac
injury, and highlight the gaps in knowledge for future research.
PMID- 29958876
TI - Commentary to "Who, where, and why are patients lost to follow up? A 20-year
study of bladder exstrophy patients at a single institution".
PMID- 29958877
TI - Canadian physician survey on the medical management of hereditary angioedema.
AB - BACKGROUND: Hereditary angioedema (HAE) is a rare disease that has significant
morbidity and may be potentially fatal because of airway obstruction. OBJECTIVE:
To determine practice patterns in physicians treating HAE. METHODS: A survey was
designed to determine HAE practice patterns among Canadian physicians. These
physicians were identified by sending the survey to members of 3 physician
organizations (Canadian Hereditary Angioedema Network, Canadian Society of
Clinical Immunology and Allergy, and Canadian Hematology Society). RESULTS:
Thirty-six physicians responded to the survey. Thirty-four physicians were
included in the analysis. Most referrals to HAE-treating physicians were from
family and emergency department physicians. The most common sites of swelling
reported by patients to physicians were facial, peripheral, and abdominal. A mean
of 53.9% of patients with type 1 and 2 HAE and 53.4% of patients with HAE with
normal C1 esterase inhibitor were undergoing long-term prophylaxis. A mean of
41.9%, 19.4%, and 93.5% of respondents had some patients taking danazol,
tranexamic acid, and C1-esterase inhibitor, respectively. Most physicians
believed that severity and frequency of attacks were the most important
determinants in deciding when to use prophylaxis. A mean of 88.2% of physicians
used C1-esterase inhibitor to treat acute attacks and 79.4% used icatibant. All
respondents were aware of HAE guidelines. CONCLUSION: Physicians are using
guidelines to support their practice and using agents suggested by guidelines
with confidence. C1 inhibitor is being used widely for prophylaxis and treatment
of acute attacks along with icatibant. However, certain special patient
populations may require additional focus in future guidelines.
PMID- 29958878
TI - Ghrelin, corticosterone and the resumption of migration from stopover, an
automated telemetry study.
AB - The spectacular natural phenomenon of avian migration is evidently shaped by
physical factors, but we know little about the underlying physiological
regulation. This contrast is especially apparent for the process of departure on
a migratory flight. The decision to resume migration is shaped by a suite of
departure cues from innate rhythms, and intrinsic and extrinsic factors. It
currently appears that these departure cues are translated into actual departure
by the hormone corticosterone, but other hormones may play a role too and
probably interact with corticosterone. We captured this concept here by
investigating the role of the hormone ghrelin and its interaction with
corticosterone for the departure decision in a migratory songbird. Ghrelin
functions as an appetite-regulating hormone. It has also been suggested to be
involved in the regulation of departure by upregulating corticosterone in
migrants ready to depart, and by facilitating the breakdown of lipids to fuel
migratory flight. We measured plasmatic ghrelin and corticosterone levels in
migrating common blackbirds (Turdus merula) at an autumnal stopover site, and
determined their departure timing with the use of a fully-automated radio
telemetry system. Against our expectations, ghrelin level was not correlated with
the birds' lipid stores or with corticosterone level. Furthermore, departure
likelihood and nocturnal departure time were not associated with ghrelin levels.
Our study thus does not support the idea that ghrelin is involved in the
regulation of departure from stopover, at least not in common blackbirds. We
discuss possible reasons for the lack of confirmation of our expectations.
PMID- 29958879
TI - Low serum alkaline phosphatase activity due to asymptomatic hypophosphatasia in a
teenage girl.
AB - OBJECTIVE: The case report details an unusual presentation of a teenage patient
with hypophosphatasia. PATIENT AND METHODS: A 17 year-old female patient
presented to endocrinology for the evaluation of fatigue and possible adrenal
insufficiency. In the course of her clinical evaluation she was noted to have a
low serum alkaline phosphatase activity. Relatively few conditions are associated
with a low serum alkaline phosphatase including Wilson's disease,
hypophosphatasia, pernicious anemia and untreated hypothyroidism. RESULTS:
Laboratory testing for hypothyroidism were unrevealing, as were the results for
vitamin B12 and vitamin D. Testing for Wilson's disease revealed a ceruloplasmin
concentration of 165 mg/L (Reference Interval, 160-450 mg/L), however sequencing
of the ATP7B gene revealed no deleterious mutations. Measurement of serum
pyridoxal phosphate and urine phosphoethanolamine for the diagnosis of
hypophosphatasia revealed concentrations of 541.5 nmol/L (reference interval:
29.6-295.5) and 707 mmol/mol creatinine (reference interval: <778 mmol/mol
creatinine), respectively, consistent with a diagnosis of hypophosphatasia.
CONCLUSIONS: Hypophosphatasia was initially considered an unlikely diagnosis for
this patient given her lack of characteristic skeletal abnormalities. This
diagnosis of hypophosphatasia in this case was complicated by a serum
ceruloplasmin concentration at the lower end of the reference interval leading to
the genetic testing for Wilson's disease.
PMID- 29958880
TI - Non-invasive prenatal aneuploidy testing: Critical diagnostic performance
parameters predict sample z-score values.
AB - OBJECTIVES: Non-invasive prenatal aneuploidy testing (NIPT) by next-generation
sequencing of circulating cell-free DNA in maternal plasma relies on chromosomal
ratio (chrratio) measurements to detect aneuploid values that depart from euploid
ratios. Diagnostic performances are known to depend on the fraction of fetal DNA
(FF) present in maternal plasma, although how this translates into specific
quantitative changes in specificity/positive predictive values and which other
variables might also be important is not well understood. DESIGN & METHODS: To
explore this issue, theoretical relationships between FF and various measures of
diagnostic performances were assessed for a range of parameter values. Empirical
data from three NIPT assays were then used to validate theoretical calculations.
RESULTS: For a given positivity threshold, dramatic changes in specificity and
positive predictive values (PPV) as a function of both FF and the coefficient of
variation (CV) of the chrratio measurement were observed. Theoretically predicted
and observed chrratio z-scores agreed closely, confirming the determinant impact
of small changes in both FF and chrratio CV. CONCLUSIONS: Evaluation of NIPT
assay performances therefore requires knowledge of the FF distribution in the
population in which the test is intended to be used and, in particular, of the
precise value of the assay chrratio CV for each chromosome or genomic region of
interest. Laboratories offering NIPT testing should carefully measure these
parameters to ensure test reliability and clinical usefulness in interpreting
individual patients' results.
PMID- 29958882
TI - A CRISPR-dCas Toolbox for Genetic Engineering and Synthetic Biology.
AB - Programmable control of gene expression is essential to understanding gene
function, engineering cellular behaviors, and developing therapeutics. Beyond the
gene editing applications enabled by the nuclease CRISPR-Cas9 and CRISPR-Cas12a,
the invention of the nuclease-dead Cas molecules (dCas9 and dCas12a) offers a
platform for the precise control of genome function without gene editing. Diverse
dCas tools have been developed, which constitute a comprehensive toolbox that
allows for interrogation of gene function and modulation of the cellular
behaviors. This review summarizes current applications of the dCas tools for
transcription regulation, epigenetic engineering, genome imaging, genetic
screens, and chromatin immunoprecipitation. We also highlight the advantages and
existing challenges of the current dCas tools in genetic engineering and
synthetic biology, and provide perspectives on future directions and
applications.
PMID- 29958881
TI - Expression profile of human tissue kallikrein 15 provides preliminary insights
into its roles in the prostate and testis.
AB - BACKGROUND: Human tissue kallikrein 15 (KLK15) is the latest member of the
kallikrein-related peptidase family. Little is known about the pathophysiological
roles of KLK15. Previous studies implied a role of KLK15 in prostate cancer.
METHODS: In the present study, we examined KLK15 protein expression using a new
immunoassay (ELISA) and immunohistochemistry (IHC). RESULTS: Highest KLK15 levels
were detected in the testis and seminal fluid, whereas lower levels were observed
in prostate and other tissues. Immunohistochemical analysis of testis suggests
that KLK15 is strongly expressed in mature spermatids, but not in immature germ
cells. KLK15 displayed predominantly nuclear localization in the basal cell layer
of the prostatic epithelium. We also measured KLK15 in supernatants of various
cell lines. Highest KLK15 levels were primarily detected in prostate cancer cell
lines and KLK15 expression was hormone-independent, in contrast to KLK3.
CONCLUSIONS: Collectively, our data provide insights into the localization and
possible role of KLK15 in human physiology.
PMID- 29958883
TI - Role of nucleocytoplasmic transport in interphase microtubule organization in
fission yeast.
AB - The proper organization of microtubules is essential for many cellular functions.
Microtubule organization and reorganization are highly regulated during the cell
cycle, but the underlying mechanisms remain elusive. Here we characterized
unusual interphase microtubule organization in fission yeast nuclear export
mutant crm1-124. The mutant cells have an intranuclear microtubule bundle during
interphase that pushes the nuclear envelope to assume a protruding morphology. We
showed that the formation of this protruding microtubule bundle requires the
nuclear accumulation of two microtubule-associated proteins (MAPs), Alp14/TOG and
Mal3/EB1. Interestingly, the forced accumulation of Alp14 in the nucleus of wild
type cells is sufficient to form the intranuclear microtubule bundle.
Furthermore, the frequency of the intranuclear microtubule formation by Alp14
accumulated in the nucleus is prominently increased by a reduction in the
nucleation activity of interphase cytoplasmic microtubules. We propose that
properly regulated nucleocytoplasmic transport and maintained activity of
cytoplasmic microtubule nucleation during interphase are important for the proper
organization of interphase cytoplasmic microtubules.
PMID- 29958884
TI - Effects of amiloride on physiological activity of stem cells of human lung cancer
and possible mechanism.
AB - Lung cancer is a common malignant tumor, the cancer stem cells (CSCs) were
regarded responsible for the development of cancer tissue. The effects of
amiloride on lung cancer stem cells and the possible mechanism were not much
investigated. In this study, human NCI-H1975 lung CSCs were selected by flow
cytometry, and the effects of amiloride at different concentrations (0, 12.5, 25,
50, and 100 MUmol/L) were evaluated on proliferation, migration, invasion and
apoptosis of CSCs using cell counting kit-8 and Transwell migration assays as
well as flow cytometry. Wstern blot analysis was performed to investigate the
effect of amiloride on the level of proteins in uPA system, NF-kB pathway, and
PI3K-AKT-mTOR pathway in CSCs. As a result, we found that amiloride inhibited
proliferation, migration and invasion of lung CSCs, and promoted apoptosis.
Further, we found that amiloride decreased levels of target proteins in the uPA
system, as well as the NF-kB and PI3K-AKT-mTOR pathways. These results indicated
that amiloride could inhibit proliferation, migration and invasion of lung CSCs,
and promotes apoptosis, these effects may be related to decreased levels of
proteins in the uPA system, the NF-kB pathway, and the PI3K-AKT-mTOR pathway.
PMID- 29958885
TI - SALL4 suppresses reactive oxygen species in pancreatic ductal adenocarcinoma
phenotype via FoxM1/Prx III axis.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a major malignant phenotype in
pancreatic cancer, which is one of the most death causes by cancer in the world.
PDAC developed from pancreatic intra-epithelial neoplasms (PanINs) and poorly
diagnosed at early stages. Beside of high drug resistance, metastasis is the
great concern during pancreatic cancer treatment. SALL4 expression is inherent in
the upregulations of endothelial mesenchymal transition (EMT) genes and therefore
promoting cancer metastasis. Furthermore, some of evidences indicated reactive
oxygen species (ROS) is also influent to metastasis and self-antioxidant capacity
seems a gold standard for successful metastasis rate. In this study, we have
found the role Spalt like protein 4 (SALL4) to PDAC proliferation, mobility and
its regulation to mitochondrial ROS via FoxM1/Prx III axis. It is possible that
SALL4 mainly induces endothelial-mesenchymal transition (EMT) phenotype and
favors ROS loss to facilitate metastasis efficiency in PDAC cells. Therefore,
SALL4 might be a promising marker for PDAC treatment and targeting SALL4 would
benefit anti-proliferative and anti-metastasis therapies.
PMID- 29958886
TI - Epithelial cell adhesion molecule expression in hepatic stem/progenitor cells is
controlled by the molecular clock system.
AB - The circadian rhythm, which regulates various body functions, is
transcriptionally controlled by a series of clock gene clusters. The clock genes
are related to the pathology of various kinds of diseases. Although there is
evidence of serious sleep disorders in patients with chronic hepatitis, the liver
regeneration mechanism under chronic hepatitis conditions and its association
with the clock genes are not clear. In this study, the influence of the circadian
locomotor output cycles kaput (CLOCK), which is one of the clock genes, on a 3,5
diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced hepatitis animal model was
investigated. The appearance of potential hepatic stem-like cells (epithelial
cell adhesion molecule [EpCAM]-positive cells) is an initial critical step in
liver regeneration during chronic inflammation. The results showed a considerable
number of hepatic EpCAM-positive cells in the wild-type (WT) mice 1 week after
the DDC feeding. However, the number of EpCAM-positive cells in the Clock-mutant
(Clk/Clk) mice decreased, and their hepatitis was worse compared with the WT
mice. In addition, the expression of Epcam mRNA, which is a functional marker of
potential hepatic stem-like cells, was controlled by LEF1, which was regulated by
CLOCK. The results of this study will facilitate the elucidation of the liver
regeneration mechanisms, including those at the molecular level, and may assist
in the development of new treatment modalities in the future.
PMID- 29958887
TI - Interfering effects of bisphenol A on in vitro growth of preantral follicles and
maturation of oocyes.
AB - AIMS: In order to investigate the effects and mechanism of Bisphenol A (BPA) on
the growth of preantral follicles and the maturation of oocytes in vitro,
preantral follicles were harvested from mouse ovaries and in vitro cultured for
11 days with different concentrations of BPA (0, 4.5 and 45 MUM) for calculating
the percentages of antral follicles, denuded oocytes, degenerative oocytes and
the maturation rate of oocytes, besides measuring the diameter of follicles and
the thickness of cumulus cell layers. METHODS: The contents of estradiol (E2) in
the culture media on Day 4, 8 and 10 were detected by ELISA. The estrogen
receptor (ER) expression, spindle morphology and chromosome distribution in
oocytes on Day 10 and 11 were observed by immunofluorescence. Western blotting
was used to detect the expressions of growth differentiation factor 9 (GDF-9),
bone morphogenetic protein-15 (BMP-15), phosphorylated extracellular signal
regulated kinase 1 (p-Erk1) and phosphorylated Ca2+/calmodulin-dependent protein
kinase II (p-CaMKII) in the oocytes. RESULTS: Compared with control, BPA (45 MUM)
significantly reduced percentages of antral follicles (9.25% vs. 91.17%, P <
0.05) and the maturation rate of oocytes (7.61% vs. 79.83%, P < 0.05), but
increased the percentages of denuded oocytes (30.29% vs. 3.36%, P < 0.05) and
degenerative oocytes (45.70% vs. 2.45%, P < 0.05). The diameter of follicles and
the thickness of the cumulus cell layers were decreased significantly (P < 0.05).
Moreover, BPA (45 MUM) significantly decreased E2 contents in the culture medium
on Day 8 and 10 (P < 0.05) and the expressions of ER, GDF-9 and BMP-15 in oocytes
(P < 0.05). Furthermore, BPA (4.5 and 45 MUM) treatment resulted in the abnormal
spindle morphology and chromosome distribution, and the decreased expressions of
p-Erk1 and p-CaMKII in the MII oocytes. CONCLUSION: Together, these results
clearly demonstrated BPA retarded the preantral follicle growth in vitro through
interfering with the synthesis and secretion of E2 and reducing the expressions
of ER, GDF-9 and BMP-15, and led to the abnormal meioses of oocytes through
reducing p-Erk1 and p-CaMKII expressions in the preantral follicles, which will
help us to further unsderstand the mechanism of BPA exposure retarding in vitro
growth of preantral follicles and maturation of oocyes.
PMID- 29958888
TI - Hypothesis: Postprandial remnant lipoproteins are the causal factors that induce
the insulin resistance associated with obesity.
AB - We have long thought that remnant lipoproteins (RLP) in plasma are significantly
increased as the result of disturbed lipoprotein metabolism followed by obesity
and insulin resistance. Therefore, it was believed that insulin resistance causes
and enhances RLP formation. In contrast, this hypothesis states that RLP induces
insulin resistance as the result of obesity associated with the excessive fat
intake. The majority of plasma TG increased after fat intake is TG in RLP (RLP
TG) and the majority of postprandial RLP is VLDL remnants, not CM remnants. RLP
is newly formed lipoproteins primarily for energy supply against starvation, like
blood sugar after carbohydrate intake. Since RLP bearing apoE, LPL and Lp(a)
function as ligands for the VLDL receptor, RLP interacts with the VLDL receptor
in visceral fat adipocytes and stored as TG similar to excessive blood sugar.
However, the excessive VLDL remnants induces obesity and its associated insulin
resistance, which plays a major role as the initiator of metabolic domino
effects, similar to blood sugar primarily serving as an energy supply to protect
against starvation.
PMID- 29958889
TI - Preptin is a new predictor of coronary artery calcification.
AB - BACKGROUND: We aimed to assess whether an elevated preptin level is associated
with coronary artery calcification (CAC). METHODS: Two hundred and twenty
participants with suspected cardiovascular disease were recruited. CAC was
measured using 320-row-detector dynamic volume CT, and the patients were divided
into 2 groups: the non-CAC group (with an Agatston score = 0) and the CAC group
(with an Agatston score > 0). RESULTS: The serum preptin level was significantly
elevated in the CAC group compared with the non-CAC group. In logistic regression
analysis, preptin, as well as age, gender, hypertension history and history of
beta-blocker use, were independent predictors of a positive CAC score. The
highest preptin quintile of patients had a higher CAC level compared with other
quintiles. Binary logistic regression analyses showed that the highest preptin
quintile had a 2.9-time increased odds ratio of an elevated CAC level than the
other 4 quintile patients. CONCLUSIONS: This study demonstrated that serum
preptin was associated with coronary artery calcification.
PMID- 29958890
TI - Snoring and markers of fetal and placental wellbeing.
AB - INTRODUCTION: Snoring, the symptom of partial airway obstruction during sleep, is
a common complaint during pregnancy and is associated with adverse perinatal
outcomes. Mechanisms underlying this association have not been studied. We
investigated the relationship between snoring in pregnancy and maternal serum
markers of feto-placental wellbeing. METHODS: We conducted a secondary analysis
of a cross sectional study designed to investigate perinatal outcomes of sleep
disordered breathing. Women admitted for delivery were systematically selected
and answered a questionnaire about snoring using the Multivariable Apnea
Prediction Index. Participants who had screening markers measured were included
and divided into snorers and non -snorers. Markers measured included first and
second trimester Down syndrome screening markers, reported as multiples of the
median (MoM). An additional analysis was performed with snorers categorized as
acute or chronic snorers based on duration of snoring in relation to pregnancy.
RESULTS: While significant differences were noted in co-morbid maternal medical
conditions between snorers and non-snorers, there were no significant differences
in the neonatal outcomes assessed between the two groups. No significant
differences were noted in any of the first trimester (PAPP-A) or second trimester
(AFP, uE3, hCG, inhibin-A) markers between snorers and non-snorers, p > 0.25. In
addition, no significant differences in marker levels were noted between acute
and chronic snorers. CONCLUSION: Snoring is not associated with alterations in
the markers of fetal or placental wellbeing tested here and suggests that there
are alternative mechanisms underlying the association between snoring and adverse
perinatal outcomes.
PMID- 29958891
TI - 5th generation cardiac troponin I and T assays in clinical routine - A head-to
head comparison with data from the Linz troponin (LITROP) study.
AB - BACKGROUND: In Europe, clinicians use so called high-sensitivity assays for the
measurement of cardiac troponin I and T (i.e., hs-cTnI and hs-cTnT assays, also
termed 5th generation assays) since several years. We aimed at performing a head
to-head comparison of two 5th generation assays in "real life use". METHODS: We
studied 3588 consecutive patients presenting to an emergency department. We used
both, a hs-cTnI assay from Abbott and a hs-cTnT assay from Roche in clinical
routine. We assessed (1) the capabilities of hs-cTnI and hs-cTnT for the
prediction of 3.7 year all-cause mortality; (2) discordant diagnoses of
myocardial injury by hs-cTnI and hs-cTnT according to the European gender-neutral
99th percentile upper reference limits (i.e., 26 ng/L and 14 ng/L, respectively);
and (3) analyte kinetics in patient with serial troponin measurements. RESULTS:
With respect to prognosis of all-cause mortality, the AUC of hs-cTnI was 0.81
(95% CI, 0.80-0.82), and the AUC of hs-cTnT was 0.85 (95% CI, 0.84-0.86). With
respect to discordant diagnoses, 21% of the 3588 patients were classified as
having myocardial injury by hs-cTnT but not by hs-cTnI, and < 1% were classified
as having myocardial injury by hs-cTnI but not by hs-cTnT. In the patients with
serial blood sampling, the median delta values were 6.3 ng/L and 25% for hs-cTnI,
and 4.2 ng/L and 16% for hs-cTnT. CONCLUSION: We found different characteristics
of the Abbott hs-cTnI and the Roche hs-cTnT assays, especially when using the
European gender-neutral 99th percentile upper reference limits. Clinically, these
different characteristics are related to discordant results in the diagnosis and
prognosis of patients presenting to an emergency department.
PMID- 29958892
TI - The sample that would not clot.
AB - BACKGROUND: Vitamin K is a vital component within both the intrinsic and
extrinsic coagulation cascade as certain factors (II, VII, IX, X and protein C
and S) utilize vitamin K as a cofactor during post translational modification.
Deficiency of vitamin K can result in the inability to properly form blood clots,
both in vivo and in vitro, due to reduced vitamin K dependent factor levels and
function. Vitamin K deficiency can result from congenital causes, such as VKOR or
CYP2C9 mutations, or acquired causes, such as nutritional deficiencies,
antibiotic therapy, or supra-therapeutic warfarin dosing. RESULTS: In this case
we present a patient with multifactorial vitamin K deficiency (due to nutritional
defects and multiple genetic mutations in VKOR and CYP2C9) that was exacerbated
by antibiotic and warfarin therapy during her hospital admission. CONCLUSION:
This case displays the importance of genetic testing prior to warfarin dosing and
the role antibiotics play in the coagulation cascade.
PMID- 29958893
TI - Determination of serum carbohydrate-deficient transferrin by a nephelometric
immunoassay for differential diagnosis of alcoholic and non-alcoholic liver
diseases.
AB - BACKGROUND: Carbohydrate-deficient transferrin is a biological marker of
excessive drinking. The aim of this study was to evaluate the diagnostic value of
a direct nephelometric immunoassay for the differential diagnosis of alcoholic
and non-alcoholic liver diseases in comparison with gamma glutamyl transferase.
METHODS: Serum samples were obtained from 305 subjects, including 122 patients
with alcoholic and 102 cases with non-alcoholic liver diseases. Serum levels of
carbohydrate-deficient transferrin were expressed as a percentage of total
transferrin. RESULTS: Serum % carbohydrate-deficient transferrin levels were
significantly higher in patients with alcoholic than with non-alcoholic liver
diseases. Carbohydrate-deficient transferrin had better specificity than gamma
glutamyl transferase to differentiate between alcoholic and non-alcoholic liver
diseases.There were 8 alcoholic liver disease patients with normal gamma glutamyl
transferase levels, and carbohydrate-deficient transferrin was significantly
elevated in 6 of them. On the other hand, there were 25 non-alcoholic liver
disease patients with elevated gamma glutamyl transferase levels; their
carbohydrate-deficient transferrin levels were within the reference intervals in
all cases. CONCLUSION: This simple carbohydrate-deficient transferrin immunoassay
is useful to detect so-called gamma glutamyl transferase non-responding drinkers
and also to exclude the possible role of excessive drinking in apparently non
alcoholic liver diseases. A large-scale prospective study is needed to further
confirm the diagnostic utility of carbohydrate-deficient transferrin.
PMID- 29958894
TI - A phylogenetic view of the leukocyte ectonucleotidases.
AB - The leukocyte ectonucleotidases are a recently defined family included in the
last Human Leukocyte Differentiation Antigens Workshop, giving prominence to
these membrane proteins whose catalytic activity is expressed outside the cell.
Among the most important substrates of the leukocyte ectonucleotidases are
extracellular ATP and NAD+ whose transient increases are not immunologically
silent but rather perceived as danger signals by the host. Among the host
responses to the release of ATP, NAD+ and related small molecules is their
breakdown on behalf of a panel of leukocyte ectonucleotidases - CD38, CD39, CD73,
CD157, CD203a and CD203c -, whose activities are concatenated to form two
nucleotide-catabolizing channels defined as the canonical and non-canonical
adenosinergic pathways. Here, after briefly reviewing the structure and function
of the proteins involved in these pathwys, we focus on the genes encoding the
ectoenzymes of these adenosinergic pathways. The chromosomal localizations of the
enzyme-encoding genes yield a first level of information concerning their origins
by duplication and modes of regulation. Further information was obtained from
phylogenetic analyses that show ectoenzyme orthologs are conserved in major
tetrapod species whereas examination of synteny conservation revealed that the
chromosomal regions harboring the ADP-ribosyl cyclases on human chromosome 4 and
the ENTPDase CD39 on chromosome 10 show striking similarities in gene content
consistent with their being paralogous chromosomal regions derived from a
vertebrate whole genome duplication. Thus the connections between some of the
leukocyte ectoenzymes run deeper than previously imagined.
PMID- 29958895
TI - Steroid bioconjugation to a CYP3A4 allosteric site and its effect on substrate
binding and coupling efficiency.
AB - Human cytochrome P450 3A4 (CYP3A4) is an important drug metabolizing enzyme
involved in a number of drug-drug and food-drug interactions. As such, much
effort has been devoted into investigating its mechanism of interaction with
ligands. CYP3A4 has one of the highest levels of substrate promiscuity for an
enzyme, and can even bind multiple ligands simultaneously. The location and
orientation of these ligands depend on the chemical structure and stoichiometry,
and are generally poorly understood. In the case of the steroid testosterone, up
to three copies of the molecule can associate with the enzyme at once, likely two
in the active site and one at a postulated allosteric site. Recently, we
demonstrated that steroid bioconjugation at the allosteric site results in an
increase in activity of CYP3A4 toward testosterone and 7-benzyloxy-4
trifluoromethylcoumarin oxidation. Here, using the established bioconjugation
methodology, we show how steroid bioconjugation at the allosteric site affects
the heme spin state, the binding affinity (KS) of CYP3A4 for testosterone, as
well as the enzyme coupling efficiency.
PMID- 29958896
TI - Effects of miR-200b-3p inhibition on the TRPC6 and BKCa channels of podocytes.
AB - Transient receptor potential canonical 6 (TRPC6) and large-conductance Ca2+
activated K+ channels (BKCa), two of the key ion channels for blood filtration
function of podocytes, have been implicated in the pathogenesis of kidney
diseases. Moreover, it has been reported that miR-200 b plays an important role
in regulating the biological processes of podocytes. In this study, we aimed to
examine whether there was a relationship between miR-200 b-3p and the two ion
channels. It was suggested that miR-200 b-3p down-regulation inhibited the
currents of TRPC6 and BKCa channels. It also showed that miR-200 b-3p inhibition
reduced the levels of protein expression and mRNA transcription of TRPC6 and BKCa
channels. Moreover, the down-regulation of miR-200 b-3p resulted in the decrease
of the intracellular Ca2+ concentration. It was also suggested that the decrease
of BKCa currents resulting from miR-200 b-3p inhibition could be regulated by
TRPC6 channels. TRPC6 blockage also inhibited BKCa currents and reduced the level
of BKCa expression. These results together suggested that miR-200 b-3p inhibition
reduced the currents of TRPC6, which led to the decrease of intracellular Ca2+
concentration. The decrease of Ca2+ source required for BKCa activation may
result in the inhibition of BKCa currents.
PMID- 29958897
TI - Intestinal beta-carotene bioconversion in humans is determined by a new single
sample, plasma isotope ratio method and compared with traditional and modified
area-under-the-curve methods.
AB - The vitamin A value (bioefficacy) of provitamin A carotenoids is determined by
absorption of the carotenoid (bioavailability) and its subsequent conversion to
retinol (bioconversion). Here we show that intestinal bioconversion of beta
carotene can be estimated based on analysis of a single plasma sample collected 6
h after subjects ingest a test dose of stable isotope-labeled beta-carotene from
the ratio of retinyl esters to retinyl esters plus beta-carotene. Plasma isotope
ratio predictions of bioconversion ranged from 50 to- 93% (mean 76%) for 45
healthy young adults with low vitamin A stores. Results were the same as
predictions made by a traditional area-under-the-curve method calculated from 0
to- 8 h or a modified area-under-the-curve method calculated from 0 to- 12 h. The
modified method may provide better estimates of bioconversion between 8 and 24 h
after ingestion of a carotenoid dose when stable isotopes cannot be used due to
cost or logistics. Furthermore, because the plasma isotope ratio method requires
only one blood sample and no isolation of triglyceride-rich lipoproteins, its use
will facilitate estimation of provitamin A carotenoid bioconversion in human
subjects and especially children, in whom repeated blood sampling is not
feasible.
PMID- 29958898
TI - An optogenetic approach to control protein localization during embryogenesis of
the sea urchin.
AB - Light inducible protein-protein interactions have been used to manipulate protein
localization and function in the cell with utmost spatial and temporal precision.
In this technical report, we use a recently developed optogenetic approach to
manipulate protein localization in the developing sea urchin embryo. A
photosensitive LOV domain from Avena sativa phototropin1 cages a small peptide
that binds the engineered PDZ domain (ePDZ) upon blue light irradiation. Using
this system, mCherry tagged proteins fused with the LOV domain were recruited to
ectopic sub-cellular regions such as the membrane, microtubules, or actin by GFP
tagged proteins fused with the ePDZ domain upon blue light irradiation within 1-3
min in the sea urchin embryo. The efficiency and speed of recruitment of each
protein to its respective subcellular region appeared to be dependent on the
power and duration of laser irradiation, as well as the respective level of
affinity to the tagged location. Controlled laser irradiation allowed partial
recruitment of the spindle to the membrane, and resulted in cell blebbing. Vasa,
a cell cycle and germline factor that localizes on the spindle and enriches in
the micromeres at 8-16 cell stage was recruited to ectopic sites, preventing
normal enrichment. Continuous blue light activation with a regular blue aquarium
light over two days of culture successfully induced LOV-ePDZ binding in the
developing embryos, resulting in continued ectopic recruitment of Vasa and
failure in gastrulation at Day 2. Although some cytotoxicity was observed with
prolonged blue light irradiation, this optogenetic system provides a promising
approach to test the sub-cellular activities of developmental factors, as well as
to alter protein localization and development during embryogenesis.
PMID- 29958899
TI - Cadherin-6B proteolytic N-terminal fragments promote chick cranial neural crest
cell delamination by regulating extracellular matrix degradation.
AB - During epithelial-to-mesenchymal transitions (EMTs), chick cranial neural crest
cells simultaneously delaminate from the basement membrane and segregate from the
epithelia, in part, via multiple protease-mediated mechanisms. Proteolytic
processing of Cadherin-6B (Cad6B) in premigratory cranial neural crest cells by
metalloproteinases not only disassembles cadherin-based junctions but also
generates shed Cad6B ectodomains or N-terminal fragments (NTFs) that may possess
additional roles. Here we report that Cad6B NTFs promote delamination by
enhancing local extracellular proteolytic activity around neural crest cells
undergoing EMT en masse. During EMT, Cad6B NTFs of varying molecular weights are
observed, indicating that Cad6B may be cleaved at different sites by A
Disintegrin and Metalloproteinases (ADAMs) 10 and 19 as well as by other matrix
metalloproteinases (MMPs). To investigate Cad6B NTF function, we first generated
NTF constructs that express recombinant NTFs with similar relative mobilities to
those NTFs shed in vivo. Overexpression of either long or short Cad6B NTFs in
premigratory neural crest cells reduces laminin and fibronectin levels within the
basement membrane, which then facilitates precocious neural crest cell
delamination. Zymography assays performed with supernatants of neural crest cell
explants overexpressing Cad6B long NTFs demonstrate increased MMP2 activity
versus controls, suggesting that Cad6B NTFs promote delamination through a
mechanism involving MMP2. Interestingly, this increase in MMP2 does not involve
up-regulation of MMP2 or its regulators at the transcriptional level but instead
may be attributed to a physical interaction between shed Cad6B NTFs and MMP2.
Taken together, these results highlight a new function for Cad6B NTFs and provide
insight into how cadherins regulate cellular delamination during normal
developmental EMTs as well as aberrant EMTs that underlie human disease.
PMID- 29958900
TI - Organ and tissue fibrosis: Molecular signals, cellular mechanisms and
translational implications.
AB - Fibrosis denotes excessive scarring, which exceeds the normal wound healing
response to injury in many tissues. Although the extracellular matrix deposition
appears unstructured disrupting the normal tissue architecture and subsequently
impairing proper organ function, fibrogenesis is a highly orchestrated process
determined by defined sequences of molecular signals and cellular response
mechanisms. Persistent injury and parenchymal cell death provokes tissue
inflammation, macrophage activation and immune cell infiltration. The release of
biologically highly active soluble mediators (alarmins, cytokines, chemokines)
lead to the local activation of collagen producing mesenchymal cells such as
pericytes, myofibroblasts or Gli1 positive mesenchymal stem-like cells, to a
transition of various cell types into myofibroblasts as well as to the
recruitment of fibroblast precursors. Clinical observations and experimental
models highlighted that fibrosis is not a one-way road. Specific mechanistic
principles of fibrosis regression involve the resolution of chronic tissue
injury, the shift of inflammatory processes towards recovery, deactivation of
myofibroblasts and finally fibrolysis of excess matrix scaffold. The thorough
understanding of common principles of fibrogenic molecular signals and cellular
mechanisms in various organs - such as liver, kidney, lung, heart or skin - is
the basis for developing improved diagnostics including biomarkers or imaging
techniques and novel antifibrotic therapeutics.
PMID- 29958901
TI - Building a Rehabilitative Care Measurement Instrument to Improve the Patient
Experience.
AB - OBJECTIVE: To develop and test face and content validity, and user interface
design of a rehabilitative care patient experience measure. DESIGN: Mixed
methods, cross-sectional validation study that included subject matter expert
input. Cognitive interviewing tested user interface and design. SETTING:
Outpatient rehabilitative care settings. PARTICIPANTS: Subject matter experts
(n=3), health care providers (n=137), and patients and caregivers (n=5)
contributed to the question development. Convenience and snowball sampling were
used to recruit rehabilitative care patients postdischarge (n=9) for cognitive
interviews to optimize survey design and user interface (N=154). INTERVENTIONS:
Not applicable. MAIN OUTCOME MEASURE: This novel survey instrument measures 6
concepts previously identified as key to outpatient rehabilitative care patients'
experience: ecosystem issues, client and informal caregiver engagement, patient
and health care provider relations, pain and functional status, group and
individual identity, and open-ended feedback. RESULTS: 502 survey questions from
psychometrically tested instruments, secondary data from a related ethnographic
study, and consultations with health care providers, patients, caregivers, and
subject matter experts, were analyzed to create a 10-item questionnaire
representing 6 key constructs that influence patient experience quality.
Cognitive interviewing with 9 patients (3 rounds of 3 participants each),
produced 3 progressively edited versions of the survey instrument. A final
version required no further modifications. DISCUSSION: Rehabilitative care
clients have characteristics that differentiate their experience from that of
other sectors and patient groups, warranting a distinct experience measure. The
survey instrument includes a parsimonious set of questions that address strategic
issues in the ongoing improvement of care delivery and the patient experience in
the rehabilitative care sector. CONCLUSION: The rehabilitative care patient
experience survey instrument developed has an acceptable user interface, and
content and face validity. Psychometric testing of the survey instrument is
reported elsewhere.
PMID- 29958902
TI - The Development of a New Computer Adaptive Test to Evaluate Anxiety in Caregivers
of Individuals With Traumatic Brain Injury: TBI-CareQOL Caregiver-Specific
Anxiety.
AB - OBJECTIVE: To design a new measure of caregiver-specific anxiety for use in
caregivers of individuals with traumatic brain injury (TBI), the Traumatic Brain
Injury Caregiver Quality of Life (TBI-CareQOL) Caregiver-Specific Anxiety item
bank. DESIGN: Cross-sectional survey study. SETTING: Three TBI Model Systems
rehabilitation hospitals, an academic medical center, and a military medical
treatment facility. PARTICIPANTS: Three hundred forty-four caregivers of
civilians with TBI and 216 caregivers of service members/veterans with TBI
(N=560). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: TBI-CareQOL
Caregiver-Specific Anxiety item bank. RESULTS: The retention of 40 Caregiver
Specific Anxiety items was supported by exploratory and confirmatory factor
analyses. Graded response model (GRM) and differential item functioning analyses
supported the retention of 33 items in the final measure. Expert review and GRM
calibration data was used to select a 6-item static short form, and GRM
calibration data was used to program the TBI-CareQOL Caregiver-Specific Anxiety
computer adaptive test (CAT). CONCLUSIONS: Established, rigorous measurement
development standards were used to develop the new TBI-CareQOL Caregiver-Specific
Anxiety CAT and corresponding 6-item short form. This measure is the first
patient-reported outcome measure designed to assess caregiver-specific anxiety in
caregivers of individuals with TBI. The measure exhibits strong psychometric
properties.
PMID- 29958903
TI - Maximum Walking Speed at Discharge Could Be a Prognostic Factor for Vascular
Events in Patients With Mild Stroke: A Cohort Study.
AB - OBJECTIVE: To identify the prognostic value of physical activity-related factors
as well as known vascular risk factors for vascular events in mild ischemic
stroke (MIS). DESIGN: Single-center prospective cohort study. SETTING: University
hospital. PARTICIPANTS: Consecutive patients (N=255) (175 men, median age 70.0y)
with acute ischemic stroke and transient ischemic attack (TIA) with modified
Rankin scale scores ranging from 0 to 2 were enrolled in this study.
INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Enrolled patients were
followed up for composite vascular events as primary outcomes up to 3 years
postdischarge. Primary outcomes included stroke and cardiovascular death,
hospitalization due to stroke or TIA recurrence, cardiovascular disease, and
peripheral artery disease. During hospitalization, known vascular risk factors
such as previous history of vascular events, stroke subtype, white matter
lesions, and ankle-brachial index were assessed. Moreover, at the time of
discharge, physical activity-related factors such as maximum walking speed (MWS),
handgrip strength, knee extensor isometric muscle strength, anxiety, and
depression were assessed as potential predictors. RESULTS: The Kaplan-Meier
estimates of cumulative risk of composite vascular events at 1, 2, and 3 years
were 9.6%, 14.4%, and 15.2%, respectively. After multivariate analysis, cerebral
white matter lesions of periventricular hyperintensity (PVH) (grade=3; hazard
ratio: 2.904; 95% confidence interval: 1.160 to 7.266; P=.023) and MWS (<1.45m/s;
hazard ratio: 2.232; 95% confidence interval: 1.010 to 4.933; P=.047) were
identified as significant independent predictors of composite vascular events.
CONCLUSIONS: The results of this study indicate that MWS could be an independent
prognostic factor for composite vascular events in MIS.
PMID- 29958905
TI - Oropharyngeal Dysphagia in Adults With Dyskinetic Cerebral Palsy and Cervical
Dystonia: A Preliminary Study.
AB - OBJECTIVES: To investigate the characteristics of oropharyngeal dysphagia in
adults with dyskinetic cerebral palsy (DCP) and cervical dystonia (CD). DESIGN:
Exploratory observational cross-sectional study. SETTING: University hospital.
PARTICIPANTS: Seventeen patients with DCP (8 men, 9 women; age, 45.7+/-6.3y)
enrolled in a randomized controlled trial on the effects of botulinum toxin
injection on CD. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Baseline
clinical assessments and videofluoroscopic swallowing studies (VFSSs) were
conducted. VFSS findings were evaluated using the videofluoroscopic dysphagia
scale (VDS) and the penetration-aspiration scale (PAS). The Gross Motor Function
Classification System (GMFCS) and Toronto Western Spasmodic Torticollis Rating
Scale (TWSTRS) scores were also assessed. Relationships between outcomes were
evaluated using Spearman's rank correlation. RESULTS: The clinical assessment
revealed abnormalities in chewing (n=10, 58.8%), tongue movement (n=10, 58.8%),
and laryngeal elevation (n=8, 47.1%). The most common abnormality on the VDS was
inadequate mastication (n=13, 76.5%), followed by premature bolus loss,
vallecular residue, and penetration/aspiration (all: n=10, 58.8%). A maximum PAS
score of 8 was observed in 8 of 17 patients (47.1%). Total and pharyngeal VDS
scores were significantly correlated with TWSTRS scores (rho=0.543, P=.024 and
rho=0.539, P=.026, respectively); the VDS oral score did not correlate with the
TWSTRS score (rho=0.446, P=.073). There was no significant correlation between
VDS score and GMFCS level (rho=0.212, P=.414). CONCLUSIONS: This preliminary
observational study presents the characteristics of oropharyngeal dysphagia in
adults with DCP and CD. Pharyngeal stage difficulties were negatively correlated
with severity of CD, but not with GMFCS level. Screening for dysphagia may be
recommended in adults with DCP and severe CD.
PMID- 29958904
TI - The development of a two new computer adaptive tests to evaluate feelings of loss
in caregivers of individuals with traumatic brain injury: TBI-CareQOL Feelings of
Loss-Self and Feelings of Loss-Person with Traumatic Brain Injury.
AB - OBJECTIVE: To develop new patient-reported outcome (PRO) measures to better
understand feelings of loss in caregivers of individuals with traumatic brain
injury (TBI). DESIGN: Cross-sectional survey study. SETTING: Three TBI Model
Systems rehabilitation hospitals, an academic medical center, and a military
medical treatment facility. PARTICIPANTS: Five-hundred-sixty caregivers of
civilians with TBI (n=344) or service members/veterans (SMVs) with TBI (n=216)
INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: TBI-CareQOL Feelings of
Loss-Self and TBI-CareQOL Feelings of Loss-Person with Traumatic Brain Injury
Item banks RESULTS: While the initial exploratory and confirmatory factor
analyses of the Feelings of Loss item pool (98 items) potentially supported a
unidimensional set of items, further analysis indicated two different factors:
Feelings of Loss-Self (43 items) and Feelings of Loss-Person with TBI (20 items).
For Feelings of Loss-Self, an additional 13 items were deleted due to item
response theory based item misfit; the remaining 30 items had good overall model
fit (Confirmatory Fit Index [CFI]=0.96, Tucker Lewis Index [TLI]=.96, Root Mean
Squared Error [RMSEA]=.10). For Feelings of Loss-Other, 1 additional item was
deleted due to an associated high correlated error modification index value; the
final 19 items evidenced good overall model fit (CFI=0.97, TLI=.97, RMSEA=.095).
The final item banks were developed to be administered as either a CAT or a short
form. Clinical experts approved the content of the 6-item short forms of the two
measures (three-week test-retest was r=.87 for Feelings of Loss-Self and r=.85
for Feelings of Loss-Person with TBI). CONCLUSIONS: The findings from this study
resulted in the development of two new PROs to assess feelings of loss in
caregivers of individuals with TBI; TBI-CareQOL Feelings of Loss-Self and TBI
CareQOL Feelings of Loss-Person with TBI. Good psychometric properties were
established and a short-form was developed for ease of use in clinical
situations. Additional research is needed to determine concurrent and predictive
validity of these measures in the psychological treatment of those caring for
persons with TBI.
PMID- 29958906
TI - ADSTEP: Preliminary Investigation of a Multicomponent Walking Aid Program in
People With Multiple Sclerosis.
AB - OBJECTIVE: To evaluate the effect of the Assistive Device Selection, Training and
Education Program (ADSTEP) on falls and walking and sitting activity in people
with multiple sclerosis (PwMS). DESIGN: Randomized controlled trial. SETTING:
Veterans affairs medical center. PARTICIPANTS: PwMS (N=40) using a walking aid at
baseline who had fallen in the previous year. INTERVENTIONS: Participants were
randomly assigned to ADSTEP or control. ADSTEP had 6 weekly, 40-minute, 1-on-1
sessions with a physical therapist, starting with walking aid selection and
fitting, followed by task-oriented progressive gait training. Control was usual
medical care with the option of ADSTEP after the study. MAIN OUTCOME MEASURES:
The following were assessed at baseline, intervention completion, and 3 months
later: falls, timed Up and Go, timed 25-foot walk, 2-minute walk, Four Square
Step Test, International Physical Activity Questionnaire, Quebec User Evaluation
of Satisfaction with Assistive Technologies, Multiple Sclerosis Walking Scale-12,
Activities-Specific Balance Confidence Scale, and Multiple Sclerosis Impact Scale
29. Effect on these outcomes was estimated by a 2-by-2 repeated measures general
linear model. RESULTS: Fewer ADSTEP than control participants fell (chi2=3.96,
P<.05. number needed to treat =3.3). Time spent sitting changed significantly
differently with ADSTEP than with control from baseline to intervention
completion (F=11.16, P=.002. ADSTEP: reduced 87.00+/-194.89min/d; control:
increased 103.50+/-142.21min/d; d=0.88) and to 3-month follow-up (F=9.25, P=.004.
ADSTEP: reduced 75.79+/-171.57min/d; control: increased 84.50+/-149.23min/d;
d=0.79). ADSTEP yielded a moderate effect on time spent walking compared to
control at 3-month follow-up (P>.05. ADSTEP 117.53+/-148.40min/d; control 46.43+/
58.55min/d; d=0.63). CONCLUSIONS: ADSTEP prevents falls, reduces sitting, and may
increase walking in PwMS.
PMID- 29958907
TI - Hydrogen exerts neuroprotective effects on OGD/R damaged neurons in rat
hippocampal by protecting mitochondrial function via regulating mitophagy
mediated by PINK1/Parkin signaling pathway.
AB - Cerebral ischemia/reperfusion injury (IRI) is a serious complication during the
treatment of stroke patients with very few effective clinical treatment. Hydrogen
(H2) can protect mitochondria function and have favorable therapeutic effects on
cerebral IRI. Mitophagy plays an important role in eliminating damaged or
dysfunctional mitochondria and maintaining mitochondria homeostasis. However,
whether the protection of H2 on cerebral IRI is via regulating mitophagy is still
unknown. In this study, OGD/R damaged hippocampal neurons were used to mimic
cerebral IRI in vivo and we detected the effect of H2, Rap (autophagy activator)
and 3-MA (autophagy inhibitor) on OGD/R neurons. The results of MTT indicated
that H2 and RAP could increase cell viability after OGD/R treatment, while 3-MA
further aggravated injury and inhibited the protection of H2 and RAP.
Furthermore, the intracellular ROS and apoptosis ratio were determined, the
results showed that ROS and apoptosis level significantly increased after OGD/R,
H2 and RAP effectively restrained the increment of ROS level and apoptosis ratio
but their protective effect can be weakened by 3-MA. Mitochondrial membrane
potential (MMP) and mitophagy level were also determined, the data showed that H2
and RAP protected against the loss of MPP and increased the co-localization of
mitochondria with GFP-LC3 while 3-MA exerted antagonistic effect. At last, the
mitophagy-related factors LC3, PINK1 and Parkin expression were detected and
analyzed. We found that the expression of LC3 was increased after OGD/R which can
be further enhanced by H2 and RAP treatment, but treatment with 3-MA was
opposite. The result revealed H2 and RAP could activate mitophagy while 3-MA
inhibit mitophagy. In addition, the study found H2 and RAP could significantly
induce the expression of PINK1 and Parkin in OGD/R neurons which was inhibited by
3-MA. Taken together, our findings demonstrated H2 had a neuroprotective effect
on OGD/R damaged neurons by protecting mitochondrial function and the potential
protection mechanism may closely related to enhancement of mitophagy mediated by
PINK1/Parkin signaling pathway.
PMID- 29958908
TI - Assessment of flow cytometry for microbial water quality monitoring in cooling
tower water and oxidizing biocide treatment efficiency.
AB - The control of Legionella proliferation in cooling tower water circuits requires
regular monitoring of water contamination and effective disinfection procedures.
In this study, flow cytometry was assessed to monitor water contamination and
disinfection treatment efficiency on bacterial cells regarding nucleic acid
injury (SYBR(r) Green II), cell integrity (SYBR(r) Green II and propidium iodide)
and metabolism activity (ChemChrome V6). A total of 27 cooling tower water
samples were analyzed in order to assess water contamination levels regarding
viable populations: standard culture, ATP measurement and flow cytometry methods
were compared. Flow cytometry and plate counts methods showed a significant
correlation for changes in concentrations despite a 1 to 2-log difference
regarding absolute quantification. Concerning intracellular activity, the use of
two different flow cytometers (FACSCantoTM II and AccuriTM C6) showed no
statistical difference while a difference was observed between flow cytometry and
usual methods (culture and ATP measurement). The standard culture and flow
cytometry methods were also compared for in vitro bacteria inactivation
measurements in the presence of 3 different types of oxidizing biocides commonly
used for cooling tower disinfection. Reductions observed ranged between 1 and 2
log depending on (1) the detection method, (2) the bacterial population origin
and/or (3) the active biocide molecule used. In conclusion, flow cytometry
represents an efficient, accurate and fast approach to monitor water
contamination and biocide treatment efficiency in cooling towers.
PMID- 29958909
TI - Deletion of pyruvate decarboxylase gene in Zymomonas mobilis by recombineering
through bacteriophage lambda red genes.
AB - Zymomonas mobilis ZM4 is a gram negative ethanologenic bacterium used in several
biotechnological applications. Metabolic engineering in this bacterium is limited
because of the available genome engineering tools. In the present study, we
report genome engineering in this bacterium using bacteriophage lambda Red genes.
Stability of plasmid replicons RK2 (pSIM9) and pBBR1 (pSIM7) containing the
lambda Red genes was found to be 78% and 74%, respectively. We demonstrate
successful deletion of pyruvate decarboxylase gene by recombineering in Z.
mobilis. The deletion was confirmed by PCR and by estimating the metabolites
formed. Ethanol, which was the main product in wild type cells, was formed in
almost negligible amount in the pdc-deleted mutant. The developed Deltapdc Z.
mobilis cells can be exploited for production of desired bioproducts by
expression of suitable enzymes that can regenerate NAD+.
PMID- 29958911
TI - Long term follow-up study of non-invasive brain stimulation (NBS) (rTMS and tDCS)
in Parkinson's disease (PD). Strong age-dependency in the effect of NBS.
AB - BACKGROUND: Transcranial magnetic stimulation (rTMS) may influence the
progression of PD compared with levodopa. The long term mind modification effect
of repeated rTMS and tDCS is not known, nor are the predictors for the effect of
NBS. OBJECTIVE/HYPOTHESIS: We hypothesized that the regularly repeated rTMS would
decrease the development of PD. Later, the treatment protocol was completed with
transcranial direct current stimulation (tDCS), supposing that there is an add-on
effect. NBS may differently influence motor and mental aspects of the disease.
METHODS: Thirty patients with PD were followed for 3.5 years in an open study.
They were stimulated with 1 Hz rTMS every half year for 1.5 years. After that the
tDCS was add to the stimulation over both sides of the cerebellum for the next 2
years. UPDRS, Trail Making Test and dual tests were used. The linear regression
lines of score systems and percentage of yearly increment were counted, analyzed
by ANOVA. RESULTS: The yearly progression rate for UPDRS total was 2% for 3.5
years, 0.6% <=65 years, 3.6% >65 years. The increment was around zero during the
rTMS + tDCS stimulations in patients <=65 years. The slope of the equation showed
the same tendency. The individual sensitivity to the NBS was high. tTMS and tDCS
>65 yrs improved pathological executive function (p < 0.0001). CONCLUSION: The
motor ability in PD was maintained at the same level in patients <=65 years with
NBS for the 3.5 years in contrast to patients >65 years. The cognitive function
of patients >65 yrs was favorable influenced by rTMS and tDCS. Age is the main
predictor of the effect of NBS. rTMS and tDCS can slow the progression of PD
without any side effects but in an age-dependent way.
PMID- 29958910
TI - Programming and Regulation of Metabolic Homeostasis by HDAC11.
AB - Histone deacetylases (HDACs) are enzymes that regulate protein functions by
catalyzing the removal of acetyl and acyl groups from lysine residues. They play
pivotal roles in governing cell behaviors and are indispensable in numerous
biological processes. HDAC11, the last identified and sole member of class IV
HDACs, was reported over a decade ago. However, its physiological function
remains poorly understood. Here, we report that HDAC11 knockout mice are
resistant to high-fat diet-induced obesity and metabolic syndrome, suggesting
that HDAC11 functions as a crucial metabolic regulator. Depletion of HDAC11
significantly enhanced insulin sensitivity and glucose tolerance, attenuated
hypercholesterolemia, and decreased hepatosteatosis and liver damage.
Mechanistically, HDAC11 deficiency boosts energy expenditure through promoting
thermogenic capacity, which attributes to the elevation of uncoupling protein 1
(UCP1) expression and activity in brown adipose tissue. Moreover, loss of HDAC11
activates the adiponectin-AdipoR-AMPK pathway in the liver, which may contribute
to a reversal in hepatosteatosis. Overall, our findings distinguish HDAC11 as a
novel regulator of obesity, with potentially important implications for obesity
related disease treatment.
PMID- 29958912
TI - Selective self-induced stimulus amplification prodrug platform for inhibiting
multidrug resistance and lung metastasis.
AB - Tumor heterogeneity is considered as one of main obstacles to limit the clinical
application of stimuli-responsive nanocarriers. Multidrug resistance (MDR) is
also a major challenge in cancer chemotherapy. Here, we developed a tumor redox
heterogeneity-responsive prodrug with self-induced reactive oxygen species (ROS)
amplification property for facilitating rapid drug release and overcoming MDR and
lung metastasis. The prodrug can self-assemble into polymer micelles (PMs) with
high drug loading content (~30%), good physiological stability, prolonged
systemic circulation and enhanced tumor distribution. Moreover, the prodrug PMs
can stimulate tumor-specific ROS signal amplification, which provided a
replenishment of consumed ROS necessary for rapid and complete drug release. The
elevated ROS could not only evoke the mitochondria-dependent apoptosis by caspase
9/3 activation, but also inhibit inherent and acquired drug resistance by
altering expression of Bcl-2 protein family and by reducing mitochondria membrane
potential (DeltaPsim) and ATP level in cancer cells. As a result, the prodrug PMs
showed enhanced efficacy for inhibiting tumor growth in S180 sarcoma tumor model
and in drug-resistant tumor model MCF-7/ADR and preventing lung metastasis in 4T1
in situ breast cancer model. This novel approach reported here may provide a
promising strategy in the design of stimuli-responsive nanocarriers for efficient
therapy of multidrug resistant and metastatic tumor.
PMID- 29958913
TI - Postmicturition syndrome: a neglected syndrome dangerous for the bladder and the
heart.
AB - Postmicturition syndrome refers to symptoms caused by overdistension of the
bladder or micturition. Bladder paraganglioma is a rare neuroendocrine neoplasm,
which arises from the chromaffin tissue of the sympathetic nervous system
embedded in the muscle layer of the bladder wall. Clinical presentation of
catecholamine-secreting paragangliomas may mimic that of hyperfunctioning adrenal
pheochromocytoma. Typical symptoms such as sweating, palpitations, headache,
nausea, hypertension, or flushing are due to catecholamine release and are
related to micturition or bladder overdistension. We herein report the case of a
22-year-old woman admitted to the Emergency Department because of cranial trauma
secondary to a car accident. She referred history of micturition-related
headache, nausea, sweating, and increase in blood pressure since she was 13 years
old. The neurological investigation was normal. No urogenital tract investigation
was performed and, on admission, blood pressure was 190/125 mmHg. During
hospitalization, abdominal ultrasonography, performed to rule out secondary
hypertension, unexpectedly showed a large vascular soft tissue mass in the
bladder wall, compatible with a paraganglioma. Twenty-four hours of urinalysis of
catecholamines revealed high values of urine metanephrines. Abdominal magnetic
resonance imaging and histopathological evaluation of the surgical specimen,
following resection of the bladder lesion, confirmed the diagnosis. Our case
underlines the importance not to underestimate symptoms compatible with
postmicturition syndrome, especially in young patients, to make early diagnosis
of bladder paraganglioma.
PMID- 29958915
TI - Microbial contamination of privacy curtains in the emergency department of a
metropolitan hospital.
PMID- 29958914
TI - Role of 5-HT1A in the nucleus of the solitary tract in the regulation of
swallowing activities evoked by electroacupuncture in anesthetized rats.
AB - Somatic stimulation therapy, such as electroacupuncture (EA), has been widely
applied in the clinic to treat dysphagia. However, its underlying mechanism has
remained unknown. In the present study, the effect of EA at acupoints Fengfu
(DU16) and Lianquan (RN23) on swallowing activities and the involvement of 5-HT1A
in the nucleus of the solitary tract (NTS) were examined in anesthetized rats. EA
at DU16 and RN23 significantly evoked myoelectric activity of the mylohyoid
muscle, which was attenuated by injection of 10 nmol 5-HT1A antagonist (WAY
100635) into the NTS. Meanwhile, 5-HT1A expression in the NTS increased following
EA. The results suggested that EA at DU16 and RN23 promotes swallowing activity,
and 5-HT1A in the NTS may play an important role in the excitatory effects.
PMID- 29958916
TI - Changes in synovial fluid and serum concentrations of cartilage oligomeric matrix
protein over 5 years after anterior cruciate ligament rupture: an exploratory
analysis in the KANON trial.
AB - OBJECTIVE: To monitor longitudinal changes of cartilage oligomeric matrix protein
(COMP) in synovial fluid (sf) and serum (s) over 5 years after acute anterior
cruciate ligament (ACL) rupture, and to compare results from two commercial COMP
immunoassays. DESIGN: Bio-fluids were collected from 121 patients on six
occasions over 5 years after acute ACL injury, and from 25 knee healthy reference
subjects. Concentrations of sf- and sCOMP were measured by AnaMar (sCOMP-Ana) and
by BioVendor (sf- and sCOMP-Bio) immunoassays; other biomarkers were previously
assessed. We used ANCOVA for group comparisons and linear mixed models for
associations between biomarkers over 5-years with P < 0.05 considered a
statistically significant difference or association. RESULTS: Compared to the
reference group, sfCOMP-Bio concentrations were 2-fold elevated within 6 weeks
after ACL injury and remained elevated 5 years thereafter, whereas sCOMP-Bio and
sCOMP-Ana concentrations were no different from reference levels at any time
point. Over the 5-year period, there was an association between sCOMP-Bio and
sCOMP-Ana concentrations, although neither sCOMP-Bio nor sCOMP-Ana associated
with sfCOMP-Bio. sfCOMP-Bio associated with SF ARGS-aggrecan, urine type I and II
collagens (uNTX-I and uCTX-II) and SF cytokines, while sCOMP-Bio associated
inversely with uCTX-II, uNTX-I and SF cytokines. CONCLUSION: The local process
after an acute ACL injury generates increased SF COMP concentrations in the
injured knee up to 5 years after injury. This response is not detected in serum.
Discrepancies in associations between sCOMP measured by BioVendor and AnaMar
immunoassays with other biomarkers indicate differences in detected COMP
fragments.
PMID- 29958917
TI - Synovial nerve fiber density decreases with naturally-occurring osteoarthritis in
horses.
AB - OBJECTIVE: To measure the nerve fiber density in synovial membranes from healthy
and OA equine joints and to investigate the relationship between synovial
innervation and OA severity, synovial vascularity and synovitis. DESIGN: Twenty
five equine metacarpophalangeal joints were collected post-mortem. The joints
were dissected and the macroscopic lesions of the articular cartilage were
scored. Synovial membrane specimens (n = 50) were harvested, fixed, sectioned and
scored histologically. Immunohistochemical staining and immunofluorescence with S
100 protein, that identifies nerve fibers, and ?-actin, that stains vascular
smooth muscle, were also performed on site-matched specimens and the
relationships between these tissues was interrogated. RESULTS: The nerve fiber
density was higher in the superficial layer (<=200 MUm) of the synovium when
compared to the deeper layer in control equine joints (mean difference (95%
C.I.): 0.054% (0.018%, 0.11%)). In osteoarthritic joints, synovial innervation
decreased in the superficial layer with increasing macroscopic OA score (beta
(SEM), 95% C.I.: -0.0061 (0.00021), -0.0011, -0.00017). The blood vessel density
was also higher in the superficial layer of the synovium compared to the deep
layer in the control (mean difference (95% C.I.): 1.1% (0.36%, 2.3%)) and OA
(mean difference (95% C.I.): 0.60% (0.22%, 1.2%)) equine joints. Moreover,
considering all synovial specimens, higher nerve fiber density in the deep layer
positively correlated with blood vessel density (beta (SEM), 95% C.I.: 0.11
(0.036), 0.035, 0.18). CONCLUSION: The reduction in nerve fiber density with
advanced cartilage degeneration suggests that peripheral neuropathy is associated
with equine OA. Whether this link is associated with neuropathic pain, requires
further investigation.
PMID- 29958918
TI - Display of the peroxiredoxin Bcp1 of Sulfolobus solfataricus on probiotic spores
of Bacillus megaterium.
AB - Bacterial spores displaying heterologous proteins have been proposed as a safe
and efficient method for delivery of antigens and enzymes to animal mucosal
surfaces. Initial studies have been performed using Bacillus subtilis spores, but
other spore forming organisms have also been considered. B. megaterium spores
have been shown capable of displaying large amounts of a model heterologous
protein (Discosoma red fluorescent protein mRFP) that in part crossed the
exosporium to localize in the space between the outer coat layer and the
exosporium. Here, B. megaterium spores have been used to adsorb Bcp1
(bacterioferritin comigratory protein 1), a peroxiredoxin of the archaeon
Sulfolobus solfataricus, known to have an antioxidant activity. The spores were
highly efficient in adsorbing the heterologous enzyme which, once adsorbed,
retained its activity. The adsorbed Bcp1 localized beneath the exosporium,
filling the space between the outer coat and the exosporium. This unusual
localization contributed to the stability of the enzyme-spore interaction and to
the protection of the adsorbed enzyme in simulated intestinal or gastric
conditions.
PMID- 29958919
TI - The effects of flutamide on cell-cell junctions in the testis, epididymis, and
prostate.
AB - In this review, we summarize recent findings on the effect of the anti-androgen
flutamide on cell-cell junctions in the male reproductive system. We outline
developmental aspects of flutamide action on the testis, epididymis, and
prostate, and describe changes in junction protein expression and organization of
junctional complexes in the adult boar following prenatal and postnatal exposure.
We also discuss findings on the mechanisms by which flutamide induces alterations
in cell-cell junctions in reproductive tissues of adult males, with special
emphasis on cytoplasmic effects. Based on the results from in vivo and in vitro
studies in the rat, we propose that flutamide affects the expression of junction
proteins and junction complex structure not only by inhibiting androgen receptor
activity, but equally important by modulating protein kinase-dependent signaling
in testicular cells. Additionally, results from studies on prostate cancer cell
lines point to a role for the cellular molecular outfit in response to flutamide.
PMID- 29958920
TI - The protective effects of sumatriptan on vincristine - induced peripheral
neuropathy in a rat model.
AB - Clinical use of vincristine (VCR), an effective chemotherapeutic agent, has been
limited due to its peripheral neuropathy toxicity. Sumatriptan, which is an anti
migraine agent is a specific agonist for 5-hydroxytryptamine 1B, 1D (5HT1B, 1D)
receptors. Several studies have shown that sumatriptan exerts anti-inflammatory
and immunomodulatory properties. This study aimed to investigate the effects of
sumatriptan on VCR-induced peripheral neuropathy in a rat model. Male Wistar rats
were intraperitoneally injected with VCR and normal saline four times per week
for 2 weeks. In the treatment group, sumatriptan (1 mg/kg) was administered
intraperitoneally 30 min prior to VCR injection every day. Mortality rate, weight
variations and histopathological changes were monitored. Hot plate, tail flick
and motor nerve conduction velocity (MNCV) tests were used to evaluate sensory
and motor neuropathy. Levels of tumor necrosis factor-alpha (TNF-alpha),
interleukin-1beta (IL-1beta) and caspase-3 in the dorsal ganglion root were
assessed by quantitative reverse transcription-PCR (qRT-PCR). Moreover, the
protein levels of p65 nuclear factor kappa B (NF- B) and phospho-p65 NF
B were examined by Western blot analysis. Co-administration of
sumatriptan with VCR significantly reversed alterations in the hot plate, tail
flick threshold and sciatic MNCV induced by VCR and also prevented mixed sensory
motor neuropathy, as indicated by better general conditions, behavioral and
electrophysiological results. In addition, sumatriptan improved the body weight
loss caused by VCR. The mRNA levels of TNF-alpha, IL-1beta and caspase-3 were
significantly diminished in the treatment group. These findings were confirmed by
histopathological analysis. In conclusion, this study demonstrated that
sumatriptan significantly attenuated VCR-induced neuropathy and could be
considered as a neuroprotective agent to prevent the VCR-induced neuropathy.
PMID- 29958921
TI - Development of a droplet digital RT-PCR for the quantification of foot-and-mouth
virus RNA.
AB - Foot-and-mouth-disease (FMD) is a highly contagious disease of domestic animals
which can result in substantial economic losses, caused by the FMD virus (FMDV).
The aim of this study was to develop and standardize a novel reverse
transcriptase droplet digital PCR (RT-ddPCR) assay for the quantification of FMDV
RNA. This assay was based upon an OIE-recognized real-time RT-PCR that detects
the 3D-encoding region of FMDV. The limit of detection at 101.4 TCID50/mL and
26.5 copies was determined using FMDV-A24-Cruzeiro-virus and a plasmid containing
the 3D-FMDV sequences, respectively. FMDV O, A and C serotypes and 11 species of
non-FMDV were used to confirm the sensitivity and specificity of the assay. The
RT-ddPCR was standardized using 60 bovine samples (representing negative and
positive samples of epithelium and/or oesophageal-pharyngeal [OP] fluid) from
animals suspected of vesicular diseases and previously tested by RT-qPCR. The RT
ddPCR showed robustness, sensitivity, specificity and accuracy, with similar
results to the RT-qPCR. Moreover, the new RT-ddPCR diagnostic tool allowed the
absolute quantification of FMDV RNA from epithelium and OP-fluid samples, as well
as having the advantages of direct quantification by endpoint, eliminating the
need for a calibration standard curve required in quantitative real-time RT-PCR.
PMID- 29958922
TI - A monoclonal antibody to DIII E protein allowing the differentiation of West Nile
virus from other flaviviruses by a lateral flow assay.
AB - West Nile Virus (WNV) belongs to the Flaviviridae family, genus Flavivirus, which
includes other emerging arthropod-borne viruses (arboviruses) pathogenic for
animals and/or humans. West Nile Virus is a genetically diverse RNA virus with at
least 7 different recognized lineages. Following its recent introduction and
subsequent expansion to the Americas, WNV is currently one of the most widely
spread arboviruses in the world having recently re-emerged in the Mediterranean
basin, Central and Eastern Europe. Laboratory tests are essential to confirm WNV
infection and monoclonal antibodies represent useful tools for the development of
diagnostic assays. A monoclonal antibody, 1D11, recognizing an epitope in the
domain III of the envelope glycoprotein of WNV, was selected for this study. Its
suitability to detect a range of WNV variants representative of its whole genetic
range, and to differentiate it from other flaviviruses and arboviruses, was
assessed by means of an immunochromatographic assay in an LFA format. A panel of
cell culture supernatants infected with 9 different WNV isolates representing a
wide range of genetic lineages, and 16 non-WNV arboviruses, including
flaviviruses closely related to WNV, were tested. The mAb correctly detected all
WNV strains, and did not react with any of the non-WNV arboviruses.
PMID- 29958923
TI - Epigallocatechin-3-gallate inhibits the early stages of Japanese encephalitis
virus infection.
AB - Epigallocatechin-3-gallate (EGCG), a green tea catechin, shows broad sepectrum
antiviral activity against many RNA and DNA viruses. This study investigated the
antiviral efficacy of EGCG against Japanese encephalitis virus (JEV), a zoonotic
flavivirus in Southeast Asia and the Western Pacific region. EGCG concentration
dependently reduced CPE, sub-G1 phase, and virus yield of infected cells with
different JEV strains at different MOIs. The antiviral activity of EGCG against
JEV in different assays declined in the following order: virus yield (IC50 of 7.0
MUM) > virus attachment (IC50 of 7.9 MUM) > virus entry (IC50 of 9.4 MUM) >
receptor binding and post-entry. However, EGCG had no virucidal effect on the
infectivity of JEV particles. The results indicated that antiviral mechanism of
EGCG against JEV was associated with blocking the early steps of JEV infection.
The study suggests EGCG as a lead compound for developing broad-spectrum
antiviral agents.
PMID- 29958924
TI - Development of an ELISA assay for screening inhibitors against divalent metal ion
dependent alphavirus capping enzyme.
AB - Alphavirus non-structural protein, nsP1 has a distinct molecular mechanism of
capping the viral RNAs than the conventional capping mechanism of host. Thus,
alphavirus capping enzyme nsP1 is a potential drug target. nsP1 catalyzes the
methylation of guanosine triphosphate (GTP) by transferring the methyl group from
S-adenosylmethionine (SAM) to a GTP molecule at its N7 position with the help of
nsP1 methyltransferase (MTase) followed by guanylylation (GT) reaction which
involves the formation of m7GMP-nsP1 covalent complex by nsP1 guanylyltransferase
(GTase). In subsequent reactions, m7GMP moiety is added to the 5' end of the
viral ppRNA by nsP1 GTase resulting in the formation of cap0 structure. In the
present study, chikungunya virus (CHIKV) nsP1 MTase and GT reactions were
confirmed by an indirect non-radioactive colorimetric assay and western blot
assay using an antibody specific for the m7G cap, respectively. The purified
recombinant CHIKV nsP1 has been used for the development of a rapid and sensitive
non-radioactive enzyme linked immunosorbent assay (ELISA) to identify the
inhibitors of CHIKV nsP1. The MTase reaction is followed by GT reaction and
resulted in m7GMP-nsP1 covalent complex formation. The developed ELISA nsP1 assay
measures this m7GMP-nsP1 complex by utilizing anti-m7G cap monoclonal antibody.
The mutation of a conserved residue Asp63 to Ala revealed its role in nsP1 enzyme
reaction. Inductively coupled plasma mass spectroscopy (ICP-MS) was used to
determine the presence of magnesium ions (Mg2+) in the purified nsP1 protein. The
divalent metal ion selectivity and investigation show preference for Mg2+ ion by
CHIKV nsP1. Additionally, using the developed ELISA nsP1 assay, the inhibitory
effects of sinefungin, aurintricarboxylic acid (ATA) and ribavirin were
determined and the IC50 values were estimated to be 2.69 MUM, 5.72 MUM and 1.18
mM, respectively.
PMID- 29958925
TI - Use of nano engineered approaches to overcome the stromal barrier in pancreatic
cancer.
AB - While chemotherapy is the only approved non-surgical option for the majority of
pancreatic cancer patients, it rarely results in a cure. The failure to respond
to chemotherapy is due to the presence of an abundant dysplastic stroma that
interferes in drug delivery and as a result of drug resistance. It is
appropriate, therefore, to consider the stromal contribution to the resistance to
chemotherapy and sidestepping this barrier with nanocarriers that improve
survival outcome. In this paper, we provide a short overview of the role of the
stroma in chemotherapy resistance, including the use of nanocarriers to negate
this barrier. We provide a perspective and guidance towards the implementation of
nanotherapeutic approaches to improve therapeutic delivery and efficacy of PDAC
management.
PMID- 29958926
TI - Clinicopathologic Characterization of Breast Carcinomas in Patients with Non-BRCA
Germline Mutations: Results from a Single Institution's High Risk Population.
AB - As multigene panel testing for hereditary cancer syndromes becomes commonplace,
germline mutations in genes other than BRCA1/2 are increasingly identified in
breast cancer patients. While histopathologic features of BRCA-mutated breast
cancers have been well-characterized, less is known about non-BRCA-related
hereditary cancers. We herein investigate the clinicopathologic characteristics
of breast cancers in women with non-BRCA germline mutations. Out of 612 women who
underwent germline testing, 16 (2.6%) of women with 18 cancers had mutations in
non-BRCA genes: ATM, CHEK2, PALB2, TP53, BMPR1A, BRIP1, MUTYH, and RAD50. An
additional two cancers were identified in a woman with a diagnosis of Bloom
syndrome (BLM mutation) who was not germline tested. Average age at diagnosis was
50 (range: 27-77), and 65% had no personal cancer history. The majority (79%) of
tumors were grade 1-2. 35% were either lobular or ductal with lobular features.
Stromal responses varied from absent to desmoplastic to sclerotic. 69% of cases
had an in situ component. With the exception of a brisk lymphocytic response in
BLM and TP53-mutated cancers, lymphocytic infiltration was mild or absent. In
summary, the majority of non-BRCA-related hereditary breast cancers represent the
patient's sentinel malignancy. Lobular features were seen in a subset and high
grade, immunogenic carcinomas were uncommon except in the setting of BLM and TP53
mutations. Overall, these findings demonstrate a range of involved genes in non
BRCA mutation carriers with breast cancer and histopathologic heterogeneity in
the associated cancers, arguing against use of histomorphology to inform panel
testing algorithms.
PMID- 29958927
TI - The role of next-generation sequencing in the differential diagnosis of composite
neoplasms.
AB - Composite neoplasms (CNs) are rare and diagnostically challenging lesions that
require differentiating between mixed clonal tumors with divergent phenotypes
(MT), collision of 2 independent tumors adjacent to each other (CT), and tumor-to
tumor metastasis (TTM). To that end, pathologists have traditionally used
immunohistochemistry and limited molecular studies, such as Sanger sequencing.
Herein we evaluate the potential application of NGS in the differential diagnosis
of these rare neoplasms. Four CNs were included in the study. Two were diagnosed
as MT (mixed adenoneuroendocrine carcinoma of the gallbladder and metastatic
papillary thyroid carcinoma with squamous dedifferentiation) and 2 were
interpreted as TTM (esophageal adenocarcinoma to lung adenocarcinoma and small
cell carcinoma of the lung to meningeal melanoma). Diagnoses were made using
clinical, histologic, and immunophenotypic information, with the aid of limited
molecular studies in 2 cases. Formalin-fixed, paraffin-embedded tissue was
dissected for DNA and RNA extraction, and NGS was performed using the Oncomine
Comprehensive Panel. The 2 tumors initially interpreted as MT showed shared
genetic aberrations in the different neoplastic components, supporting the
pathologic diagnosis. NGS results for the lesion diagnosed as esophageal
adenocarcinoma metastatic to lung adenocarcinoma did not support the
histopathologic interpretation and were deemed inconclusive. However, the
identification of an identical CDKN2A mutation in all components and in the
adjacent benign lung parenchyma suggests a possible germline aberration.
Sequencing results in the last case were clearly supportive of TTM. This study
illustrates the role of NGS in the diagnostic workup of CNs, as an adjunct to
light microscopy and immunohistochemistry.
PMID- 29958928
TI - Conditional knock-down of a novel coccidian protein leads to the formation of
aberrant apical organelles and abrogates mature rhoptry positioning in Toxoplasma
gondii.
AB - Toxoplasma gondii which is a member of the coccidian parasites owns a spatially
polarized secretory system, which synthesizes de novo micronemes and rhoptries.
These apical secretory organelles discharge their contents into host cells
promoting invasion and survival. Herein, we identified a novel Coccidian Specific
CORVET/HOPS Associated Protein (CSCHAP) belonging to the interaction network of
both tethering complexes. CSCHAP is associated with the endomembrane system,
rhoptries, micronemes and probably to the inner core of the conoid. Conditional
depletion of CSCHAP leads to apical disconnection of rhoptries, aberrant apical
organelles biogenesis and severely hinders T. gondii invasion. Overall, our study
provides new insights into the mechanisms underpinning secretory organelles
biogenesis in coccidian parasites.
PMID- 29958930
TI - Assigning methyl resonances for protein solution-state NMR studies.
AB - Solution-state NMR is an important tool for studying protein structure and
function. The ability to probe methyl groups has substantially expanded the scope
of proteins accessible by NMR spectroscopy, including facilitating study of
proteins and complexes greater than 100 kDa in size. While the toolset for
studying protein structure and dynamics by NMR continues to grow, a major rate
limiting step in these studies is the initial resonance assignments, especially
for larger (>50 kDa) proteins. In this practical review, we present strategies to
efficiently isotopically label proteins, delineate NMR pulse sequences that can
be used to determine methyl resonance assignments in the presence and absence of
backbone assignments, and outline computational methods for NMR data analysis. We
use our experiences from assigning methyl resonances for the aromatic
biosynthetic enzymes tryptophan synthase and chorismate mutase to provide advice
for all stages of experimental set-up and data analysis.
PMID- 29958929
TI - Development of a human physiologically based pharmacokinetic (PBPK) model for
phthalate (DEHP) and its metabolites: A bottom up modeling approach.
AB - DEHP exposure to human comes from different sources such as food, diet,
cosmetics, toys, medical products, and food wraps. Recently, DEHP was categorized
as non-persistent endocrine disrupting compounds (EDCs) by the world health
organization (WHO). Rat experimental studies showed that phthalate and its
metabolite(s) can cause hepatic, developmental and reproductive toxicity. In
human, DEHP rapidly metabolizes into a toxic metabolite MEHP. This MEHP further
metabolizes into the different chemical forms of 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP
and phthalic acid. A simple DEHP pharmacokinetics model has been developed, but
with a limited number of metabolites. A chemical like DEHP which extensively
metabolised indicate the need of a detail metabolic kinetics study. A
physiological based pharmacokinetics (PBPK) model of the DEHP considering all the
major metabolites in human, has not been developed yet. The objective of this
study is to develop a detailed human PBPK model for the DEHP and its major
metabolites by using a bottom-up modelling approach with the integration of a in
vitro metabolic data. This approach uses an in-vitro-in-vivo extrapolation
(IVIVE) and a quantitative structure-activity relationship (QSAR) method for the
parameterization of the model. Monte Carlo simulations were performed to estimate
the impact of parametric uncertainty onto the model predictions. First, the model
was calibrated using the control human kinetic study that represents the time
course of DEHP metabolites concentration in both the blood and the urine. Then,
the model was evaluated against the published independent data on different
dosing scenarios. The results of model predictions for the DEHP metabolites in
both the blood and the urine were well within the range of experimentally
observed data. The model also captured the similar trend of time course profile
to the observed data, shows model good predictability power. The current
developed PBPK model can futher be used for the prediction of the time course of
chemical concentrations for the different exposure scenarios not only in the
blood and the urine but also in the other compartments. Moreover, this model can
also be used to explore different biomonitoring studies for the human health risk
assessment and might be useful for integrative toxicological study in improving
exposure-target tissue dose-response relationship.
PMID- 29958931
TI - Reconstruction Techniques after Proximal Humerus Tumour Resection.
AB - Reconstruction of the proximal humerus after tumour resection is a surgical
challenge. The goal consists not only in reconstructing the resected bone
segment, but also in restoring a stable and mobile shoulder. The choice of the
technique depends on the status of the soft tissues at the end of the resection.
The pre-operative work-up must determine the oncological goals of the resection
and identify the structures that can be spared. When deltoid muscle function is
preserved, a reverse prosthesis offers the best stability and mobility outcomes.
The objective of this work is to describe the indications and techniques used in
the various available reconstruction methods. Shoulder mobilities are restored
using some of these methods and lost with others. Emphasis is put on the reverse
shoulder prosthesis, with a description of its variants (standard prosthesis,
cement sleeve, allograft-prosthesis composite, and massive prosthesis) and a
discussion of the management of its early complications. When performing reverse
shoulder arthroplasty, glenoid implant preparation and positioning are crucial to
achieve stability, and humeral length restoration will govern soft-tissue
tension. Latissimus dorsi tendon transfer is required to restore active external
rotation if the posterior rotator cuff tendons have been removed. Allograft
anatomic prosthesis composites, osteo-cartilaginous allografts, arthrodesis, and
spacer prostheses are proposed for patients in whom the local conditions preclude
implantation of a reverse shoulder prosthesis.
PMID- 29958932
TI - Misdistribution of iron and oxidative stress in chronic kidney disease.
AB - Chronic kidney disease (CKD) patients have an extremely high risk of developing
cardiovascular diseases (CVD) compared to the general population. Systemic
inflammation associated with oxidative stress could be an important determinant
of morbidity and mortality associated with CVD. We suspected that dysregulation
of iron metabolism should be considered in these patients. Anemia is prevalent in
CKD patients and is often treated with erythropoiesis-stimulating agents (ESAs)
and iron. In addition, iron administration sometimes causes iron overdose.
Excessive iron in the cytosol and mitochondria can accelerate the formation of a
highly toxic reactive oxygen species, hydroxyl radicals, which damage lipids,
proteins, and DNA. In this review, we propose the following four major reasons
for oxidative stress in CKD patients: 1) iron is sequestered in cells by
proinflammatory cytokines and hepcidin; 2) the reduction in frataxin increases
"free" iron in mitochondria; 3) the accumulation of 5-aminolevulinic acid, a heme
precursor, has toxic effects on iron and mitochondrial metabolism; and 4) the
elevated levels of the metabolic hormone, leptin, promote hepatic hepcidin
production. Although an efficient therapy for preventing oxidative stress in
these patients has not yet been well defined, we propose that ESAs for renal
anemia may ameliorate these causes of oxidative stress. Further clinical trials
are necessary to clarify the effectiveness of ESAs on oxidative stress in CKD
patients.
PMID- 29958933
TI - A free radical theory of frailty.
AB - The free radical theory of ageing provided an intellectual framework for many
laboratories working on ageing. However, experimental and clinical evidence
showing that high doses of antioxidants do not have an effect on ageing or on age
associated diseases, cast doubts on the validity of this theory. Data from our
own laboratory show that oxidative damage does not correlate with age, especially
in the geriatric population, but rather with the frailty state. This has led us
to postulate the free radical theory of frailty that proposes that oxidative
damage is associated with frailty, but not with chronological age itself.
Superoxide dismutase deficient mice are more frail than controls. But more
importantly, we have observed that animals that are protected against oxidative
damage by overexpression of antioxidant enzymes, delay the onset of frailty and
are more vigorous than controls. In this review, we describe results from both,
experimental animals and human cohorts, that lead us to the formulate this free
radical theory of frailty.
PMID- 29958934
TI - Schizosaccharomyces pombe cardiolipin synthase is part of a mitochondrial fusion
protein regulated by intron retention.
AB - Cardiolipin (CL) is a unique lipid component of mitochondria in all eukaryotes.
It is important for the architecture of mitochondrial membranes and for
mitochondrial dynamics. CL also creates a highly specific microenvironment of
mitochondrial protein machineries. CL biosynthetic pathway is, however, only
partially characterized in the fission yeast Schizosaccharomyces pombe. Here we
show that CL synthase is an essential protein in S. pombe. It is encoded by the
ORF SPAC22A12.08c as a C terminal part of a tandem fusion protein together with a
mitochondrial hydrolase of unknown function. Expression of S. pombe CL synthase
is able to complement deletion of the CRD1 gene of Saccharomyces cerevisiae and,
vice versa, S. cerevisiae CRD1 gene complements deletion of S. pombe
SPAC22A12.08c. The proper expression of CL synthase and its partner in the tandem
protein, the mitochondrial hydrolase, is regulated at the level of alternate
intron splicing. The first part of the SPAC22A12.08c fusion protein could be
translated from both major SPAC22A12.08c derived mRNAs, with and without intron
IV. Functional CL synthase, however, is produced only from the minor
SPAC22A12.08c derived mRNA that has intron IV retained. Thus, intron retention is
a novel mechanism for the differential expression of two proteins that evolved as
a fusion protein and are under the control of the same promoter.
PMID- 29958935
TI - A pilot study of the effects of a vacuum sealing barrier method for
photostimulable phosphor plates regarding plate damage and prevention of
microbiologic cross-contamination.
AB - OBJECTIVE: The aim of this study was to evaluate the effectiveness of a new
sealing method for preventing cross-contamination of photostimulable phosphor
(PSP) plates. STUDY DESIGN: Twelve new PSP plates were divided into 3 groups (PSP
a, PSP-b, and PSP- c) and placed in 3 different barriers (2 different brands of
envelopes and a vacuum sealing method). All plates were exposed to X-rays with an
aluminum step wedge, and the images were evaluated for the presence of any
artifacts. After radiography, the PSP plates were removed from the barriers. The
barriers and the PSP plates were disinfected and culture performed to assess any
microorganism burden. Subsequently, the PSP plates were coated again with all
barriers. The barriers were then contaminated and microbiologic specimens were
collected. Subsequently, the barriers were wiped with alcohol. The PSP plates
were removed, and microbiologic specimens were obtained. RESULTS: No artifacts
were recorded on the radiographic images on the sensors in any group.
Microorganisms were detected on the PSP plates placed in envelopes. No
colonization of microorganisms was detected on the vacuum sealed PSP plates.
CONCLUSIONS: The new vacuum-sealing method may be useful in preventing cross
contamination of PSP plates during radiographic procedures.
PMID- 29958936
TI - Combination therapy improves immune response and prognosis in patients with
advanced oral mucosal melanoma: A clinical treatment success.
AB - OBJECTIVE: This study was undertaken to analyze disease response and immune
response to assess treatment effectiveness and success in patients with advanced
oral mucosal melanoma treated with cytokines injection, cryosurgery, and adoptive
cell transfer therapy. STUDY DESIGN: Ten patients were enrolled in the study, and
the relevant characteristics and immunologic differences were evaluated. RESULTS:
All patients achieved an objective clinical response according to the Response
Evaluation Criteria in Solid Tumors, including 7 cases of continuing complete
remission (55, 27, 87 + , 58+, 58 + , 45 + , and 37 + months) and 3 cases of
partial remission (30, 12, and 9 months). Five responders are currently alive.
After combination therapy, we observed that the proportion of CD3+ lymphocytes
and the secretion of interferon-gamma increased, whereas interleukin-10
decreased. In the assay of improved cytokine-induced killer cells, CD4+CD25+
regulatory T cells declined, and natural killer cells upregulated. Meanwhile, the
proliferation rate of in vitro cultured improved cytokine-induced killer cells
improved after courses of therapy. CONCLUSIONS: Combination therapy of cytokine
injection, cryosurgery, and transfer of improved cytokine-induced killer cells
may be a promising approach for patients with oral mucosal melanoma.
PMID- 29958937
TI - An MRI evaluation of the effects of qat chewing habit on the temporomandibular
joint.
AB - OBJECTIVE: The aim of this study was to investigate the effects of the qat
chewing habit on the temporomandibular joint by using magnetic resonance imaging.
STUDY DESIGN: Sixty patients were included: a study group (40 qat chewers) and a
control group (20 nonchewers). On the basis of qat chewing habit duration, the
study group was subdivided into 3 further subgroups: subgroup I (5-10 years),
subgroup II (11-15 years), and subgroup III (>15 years). Data on qat chewing
habit were recorded, and a standardized clinical examination was performed.
Bilateral oblique sagittal magnetic resonance imaging sections were obtained to
evaluate disk displacement, osteoarthritis, and joint effusion. RESULTS: Clicking
and pain were diagnosed in 72.5% and 65% of study group patients, respectively.
Significant differences were discovered between the study group and the control
group in osteoarthritis and joint effusion (P= .003 and .002, respectively). With
regard to qat chewing habit duration, there were differences between study
subgroup II and subgroup III versus control group in osteoarthritis (P= .040 and
.001, respectively) and the 3 study subgroups versus control group in joint
effusion (P= .026, .004, and .001, respectively). Significant correlations were
found between osteoarthritis and clicking (P= .006) and muscle pain (P <= .044),
and between joint effusion and temporomandibular joint pain (P = .006) and muscle
pain (P <= .014). CONCLUSIONS: Qat chewing habit may be a risk factor for
temporomandibular joint disorders with high percentages of osteoarthritis and
joint effusion.
PMID- 29958938
TI - Caspase recruitment domain 6 protects against hepatic ischemia/reperfusion injury
by suppressing ASK1.
AB - BACKGROUND & AIMS: The hepatic injury caused by ischemia/reperfusion (I/R) insult
is predominantly determined by the complex interplay of sterile inflammation and
liver cell death. Caspase recruitment domain family member 6 (CARD6) was
initially shown to play important roles in NF-kappaB activation. In our
preliminary studies, CARD6 downregulation was closely related to hepatic I/R
injury in liver transplantation patients and mouse models. Thus, we hypothesized
that CARD6 protects against hepatic I/R injury and investigated the underlying
molecular mechanisms. METHODS: A partial hepatic I/R operation was performed in
hepatocyte-specific Card6 knockout mice (HKO), Card6 transgenic mice with CARD6
overexpression specifically in hepatocytes (HTG), and the corresponding control
mice. Hepatic histology, serum aminotransferases, inflammatory
cytokines/chemokines, cell death, and inflammatory signaling were examined to
assess liver damage. The molecular mechanisms of CARD6 function were explored in
vivo and in vitro. RESULTS: Liver injury was alleviated in Card6-HTG mice
compared with control mice as shown by decreased cell death, lower serum
aminotransferase levels, and reduced inflammation and infiltration, whereas Card6
HKO mice had the opposite phenotype. Mechanistically, phosphorylation of ASK1 and
its downstream effectors JNK and p38 were increased in the livers of Card6-HKO
mice but repressed in those of Card6-HTG mice. Furthermore, ASK1 knockdown
normalized the effect of CARD6 deficiency on the activation of NF-kappaB, JNK and
p38, while ASK1 overexpression abrogated the suppressive effect of CARD6. CARD6
was also shown to interact with ASK1. Mutant CARD6 that lacked the ability to
interact with ASK1 could not inhibit ASK1 and failed to protect against hepatic
I/R injury. CONCLUSIONS: CARD6 is a novel protective factor against hepatic I/R
injury that suppresses inflammation and liver cell death by inhibiting the ASK1
signaling pathway. LAY SUMMARY: The protein CARD6 plays an important role during
the process of liver blood flow restriction (ischemia) and restoration
(reperfusion). By suppressing the activity of ASK1, CARD6 can protect against
hepatocyte injury. Targeting CARD6 is a potential strategy for prevention and
treatment of ischemia/reperfusion injury.
PMID- 29958939
TI - Mutational landscape of a chemically-induced mouse model of liver cancer.
AB - BACKGROUND & AIMS: Carcinogen-induced mouse models of liver cancer are used
extensively to study the pathogenesis of the disease and are critical for
validating candidate therapeutics. These models can recapitulate molecular and
histological features of human disease. However, it is not known if the genomic
alterations driving these mouse tumour genomes are comparable to those found in
human tumours. Herein, we provide a detailed genomic characterisation of tumours
from a commonly used mouse model of hepatocellular carcinoma (HCC). METHODS: We
analysed whole exome sequences of liver tumours arising in mice exposed to
diethylnitrosamine (DEN). Mutational signatures were compared between liver
tumours from DEN-treated and untreated mice, and human HCCs. RESULTS: DEN
initiated tumours had a high, uniform number of somatic single nucleotide
variants (SNVs), with few insertions, deletions or copy number alterations,
consistent with the known genotoxic action of DEN. Exposure of hepatocytes to DEN
left a reproducible mutational imprint in resulting tumour exomes which we could
computationally reconstruct using six known COSMIC mutational signatures. The
tumours carried a high diversity of low-incidence, non-synonymous point mutations
in many oncogenes and tumour suppressors, reflecting the stochastic introduction
of SNVs into the hepatocyte genome by the carcinogen. We identified four
recurrently mutated genes that were putative oncogenic drivers of HCC in this
model. Every neoplasm carried activating hotspot mutations either in codon 61 of
Hras, in codon 584 of Braf or in codon 254 of Egfr. Truncating mutations of Apc
occurred in 21% of neoplasms, which were exclusively carcinomas supporting a role
for deregulation of Wnt/beta-catenin signalling in cancer progression.
CONCLUSIONS: Our study provides detailed insight into the mutational landscape of
tumours arising in a commonly used carcinogen model of HCC, facilitating the
future use of this model to better understand the human disease. LAY SUMMARY:
Mouse models are widely used to study the biology of cancer and to test potential
therapies. Herein, we have described the mutational landscape of tumours arising
in a carcinogen-induced mouse model of liver cancer. Since cancer is a disease
caused by genomic alterations, information about the patterns and types of
mutations in the tumours in this mouse model should facilitate its use to study
human liver cancer.
PMID- 29958940
TI - CiPA challenges and opportunities from a non-clinical, clinical and regulatory
perspectives. An overview of the safety pharmacology scientific discussion.
AB - The Safety Pharmacology Society organized a scientific session at its annual
conference in 2017 to discuss the challenges and opportunities of the
Comprehensive In-Vitro Proarrhythmia Assay (CiPA) paradigm. Our intention was to
raise awareness of this initiative with its members and also to gauge the extent
to which safety pharmacologists have incorporated the CiPA testing strategy
within the pharmaceutical industry. CiPA offers many potential opportunities
including 1) a focus on proarrhythmic risk (as opposed to QTc prolongation), 2)
providing scientific rationale to support the continued development of compounds
that may have a poor selectivity over hERG whilst also blocking other inward
currents and 3) reducing the extent of ECG monitoring in clinical trials with a
greater influence of the non-clinical studies. Such opportunities may speed drug
development and reduce costs. However, there are also challenges for CiPA
implementation. For example, the mixed ion channel paradigm does not easily lend
itself to a prospective drug discovery strategy although testing for such effects
can be achieved with assays with good throughput. However, it should also be
recognized that compounds with a mixed ion channel profile might also have
properties that are undesirable to treat non-life threatening indications. All
components of CiPA (nonclinical and clinical) require validation, particularly as
a composite package to impact drug development and evaluation. One of the
significant discussion points was that the existing regulatory guidance supports
the use of components of CiPA through follow-up studies. A survey of the
conference audience showed that the level of awareness of CiPA is quite high and
that companies are already conducting some testing against a wider panel of
cardiac ion channels beyond hERG. However, the adoption of other technologies
(stem cell derived cardiac myocytes and in silico modeling) is less well
developed. Taken together, the session demonstrated the potential advantages of
CiPA, but also some significant challenges.
PMID- 29958941
TI - When Coordinating Finger Tapping to a Variable Beat the Variability Scaling
Structure of the Movement and the Cortical BOLD Signal are Both Entrained to the
Auditory Stimuli.
AB - Rhythmic actions are characterizable as a repeating invariant pattern of movement
together with variability taking the form of cycle-to-cycle fluctuations.
Variability in behavioral measures is atypically random, and often exhibits
serial temporal dependencies and statistical self-similarity in the scaling of
variability magnitudes across timescales. Self-similar (i.e. fractal) variability
scaling is evident in measures of both brain and behavior. Variability scaling
structure can be quantified via the scaling exponent (alpha) from detrended
fluctuation analysis (DFA). Here we study the task of coordinating thumb-finger
tapping to the beats of constructed auditory stimuli. We test the hypothesis that
variability scaling evident in tap-to-tap intervals as well as in the
fluctuations of cortical hemodynamics will become entrained to (i.e. drawn
toward) manipulated changes in the variability scaling of a stimulus's beat-to
beat intervals. Consistent with this hypothesis, manipulated changes of the
exponent alpha of the experimental stimuli produced corresponding changes in the
exponent alpha of both tap-to-tap intervals and cortical hemodynamics. The
changes in hemodynamics were observed in both motor and sensorimotor cortical
areas in the contralateral hemisphere. These results were observed only for the
longer timescales of the detrended fluctuation analysis used to measure the
exponent alpha. These findings suggest that complex auditory stimuli engage both
brain and behavior at the level of variability scaling structures.
PMID- 29958942
TI - Stimulation of Acetylcholine Release and Pharmacological Potentiation of
Cholinergic Transmission Affect Cholinergic Receptor Expression Differently
during Visual Conditioning.
AB - Cholinergic stimulation coupled with visual conditioning enhances the visual
acuity and cortical responses in the primary visual cortex. To determine which
cholinergic receptors are involved in these processes, qRT-PCR was used. Two
modes of cholinergic enhancement were tested: a phasic increase of acetylcholine
release by an electrical stimulation of the basal forebrain cholinergic nucleus
projecting to the visual cortex, or a tonic pharmacological potentiation of the
cholinergic transmission by the acetylcholine esterase inhibitor, donepezil. A
daily visual exposure to sine-wave gratings (training) was paired with the
cholinergic enhancement, up to 14 days. qRT-PCR was performed at rest, 10 min,
one week or two weeks of visual/cholinergic training with samples of the visual
and somatosensory cortices, and the BF for determining mRNA expression of
muscarinic receptor subtypes (m1, m2, m3, m4, m5), nicotinic receptor subunits
(alpha3, alpha4, alpha7, beta2, beta4), and NMDA receptors, GAD65 and ChAT, as
indexes of cortical plasticity. A Kruskal-Wallis test showed a modulation of the
expression in the visual cortex of m2, m3, m4, m5, alpha7, beta4, NMDA and GAD65,
but only beta4 within the basal forebrain and none of these mRNA within the
somatosensory cortex. The two modes of cholinergic enhancement induced different
effects on mRNA expression, related to the number of visual conditioning sessions
and receptor specificity. This study suggests that the combination of cholinergic
enhancement and visual conditioning is specific to the visual cortex and varies
between phasic or tonic manipulation of acetylcholine levels.
PMID- 29958943
TI - Acute Aversive Stimuli Rapidly Increase the Activity of Ventral Tegmental Area
Dopamine Neurons in Awake Mice.
AB - The ventral tegmental area (VTA) is one of the origins of the brain dopaminergic
system and is involved in regulating various physiological functions such as pain
processing and motivation. In this study, we utilized a fiber photometry system
to specifically investigate the activity of dopamine neurons in the VTA using
dopamine transporter promoter-driven Cre recombinase-expressing mice and site
specific infection of adeno-associated virus carrying the FLEX G-CaMP6 gene. As
expected, expression of G-CaMP6 was restricted to VTA dopamine neurons. We
recorded G-CaMP6 green fluorescent signal, which reflected dopaminergic neuronal
activity, in awake mice exposed to tail pinch, ultrasonic sound, predator odor,
and a male intruder mouse. These stimuli resulted in a rapid and short-lasting
increase in the activity of VTA dopamine neurons while the control stimuli of a
gentle tail touch and appearance of empty box did not induce any changes. In
addition, fluorescence intensity was not changed by any of these stimuli in the
control animals expressing hrGFP instead of G-CaMP6 in VTA dopamine neurons. Our
data clearly show that acute aversive stimuli rapidly increase the activity of
VTA dopamine neurons and thus suggest a salience-processing role.
PMID- 29958945
TI - A mosquito bites and a butterfly flies: A specific response type of frontal
patients in a similarity task.
AB - BACKGROUND: Patients with neurodegenerative diseases affecting the frontal lobes
have difficulties in categorization tasks, such as the similarity tasks. They
give two types of unusual response to the question: "In what way are an orange
and a banana alike?", either a differentiation ("one is yellow, the other is
orange") or a concrete similarity ("they are sweet"). OBJECTIVE: To characterize
the categorization deficit of frontal patients and develop a short diagnostic
tool to assess the nature of these difficulties. METHOD: We analyzed the
responses provided by frontal and non-frontal neurodegenerative patients in a
novel verbal similarity task (SimiCat). We included 40 frontal patients with
behavioral variant fronto-temporal dementia (bvFTD) and progressive supranuclear
palsy (PSP), 23 patients with Alzheimer's disease (AD) and 41 healthy matched
controls. Responses that did not correspond to the expected taxonomic category
(e.g.: fruits) were considered as errors. RESULTS: All patients groups were
impaired at the SimiCat test compared to controls. Differentiation errors were
specific to frontal patients. Receiver operating characteristic analyses showed
that a cut-off of two differentiation errors or more achieved 85% sensitivity of
100% specificity to discriminate bvFTD from AD. A short version of the test (<5
min) showed similar discriminative validity as the full version. CONCLUSION:
Differentiation responses were specific to frontal patients. The SimiCat
demonstrates good discriminative validity to differentiate between bvFTD and AD.
The short version of the test is a promising diagnostic tool that will need
validation in future studies.
PMID- 29958944
TI - Mu Opioid Receptor Agonist DAMGO Produces Place Conditioning, Abstinence-induced
Withdrawal, and Naltrexone-Dependent Locomotor Activation in Planarians.
AB - Unlike the behavioral effects planarians display when exposed to cocaine,
amphetamines, cathinones, ethanol and sucrose, effects of opioid receptor
agonists, especially mu opioid receptor agonists, are poorly defined in these
flatworms. Here, we tested the hypothesis that planarians exposed to a selective
mu opioid receptor agonist, DAMGO (0.1, 1, 10 uM), would display a triad of
opioid-like effects (place conditioning, abstinence-induced withdrawal, and
motility changes). DAMGO was selected versus morphine because of its greater mu
opioid receptor selectivity. In place conditioning and abstinence experiments,
the planarian light/dark test (PLDT) was utilized (i.e., planarians are placed
into a petri dish containing water that is split into light and dark compartments
and time spent in the compartments is determined). Planarians conditioned with
DAMGO (1 uM) spent more time on the drug-paired side compared to water controls.
In abstinence experiments, planarians exposed to DAMGO for 30 min were removed
and then placed into water, where light avoidance (e.g. defensive responding) and
depressant-like effects (i.e., decreased motility) were quantified. Compared to
water controls, DAMGO-withdrawn planarians spent less time in the light (10 uM)
and displayed decreased motility (1, 10 uM). Acute DAMGO exposure (1 uM) produced
hypermotility that was antagonized by naltrexone (1, 10, 100 uM). In contrast,
acute exposure to the kappa opioid receptor agonist U50,488H (0.1, 1, 10 uM)
resulted in decreased motility. Our results show that a mu opioid agonist
produces mammalian-like behavioral responses in planarians that may be related to
addiction and suggest opioid-like behavioral effects are conserved in
invertebrates.
PMID- 29958946
TI - Segregating polymorphism in the NMDA receptor gene GRIN2A, schizotypy, and mental
rotation among healthy individuals.
AB - Common alleles associated with psychiatric disorders are often regarded as
deleterious genes that influence vulnerability to disease, but they may also be
considered as mediators of variation in adaptively structured cognitive
phenotypes among healthy individuals. The schizophrenia-associated gene GRIN2A
(glutamate ionotropic receptor NMDA type subunit 2a) codes for a protein subunit
of the NMDA (N-methyl-D-aspartate) receptor that underlies central aspects of
human cognition. Pharmacological NMDA blockage recapitulates the major features
of schizophrenia in human subjects, and represents a key model for the
neurological basis of this disorder. We genotyped two functional GRIN2A
polymorphisms in a large population of healthy individuals who were scored for
schizotypy and mental imagery/manipulation (the mental rotation test). Rare
allele homozygosity of the promoter microsatellite rs3219790 was associated with
high total schizotypy (after adjustment for multiple comparisons) and with
enhanced mental rotation ability (nominally, but not after adjustment for
multiple comparisons), among males. These findings provide preliminary evidence
regarding a genetic basis to previous reports of enhanced mental imagery in
schizophrenia and schizotypy. The results also suggest that some schizophrenia
related alleles may be subject to cognitive tradeoffs involving both positive and
negative effects on psychological phenotypes, which may help to explain the
maintenance of psychiatric-disorder risk alleles in human populations.
PMID- 29958947
TI - Analysis of long-non-coding RNAs associated with ethylene in tomato.
AB - Long-Non-Coding RNAs (LncRNAs) are a class of non-coding endogenous RNAs
contributing to numerous biological processes. LeERF1 is a tomato ethylene
response factor (ERF) near the end of the ethylene signal transduction pathway.
To identify lncRNAs in tomato and elucidate their roles in ethylene signaling,
deep sequencing was deployed in over-expression and repression LeERF1 transgenic
and control tomato fruits. A total of 397 lncRNAs were identified, including 169
tomato lncRNAs that had not previously been identified. Among these, 12 were
differentially expressed between the transgenic and control tomato fruits.
Numerous lncRNA target genes were identified including many associated with
ethylene signaling including auxin response factors and auxin-induced proteins, F
box proteins, ERFs and MADS-box proteins. In addition, two lncRNAs were found to
be the precursor of three miRNAs and four lncRNAs could be targeted by five
miRNAs. We propose a regulatory model highlighting the relationships between
lncRNAs and their targets involved in ethylene signal transduction which
establishes a foundation for addressing the role of LncRNAs in ethylene response.
PMID- 29958948
TI - WIP/ITSN1 complex is involved in cellular vesicle trafficking and formation of
filopodia-like protrusions.
AB - WIP (WASP interacting protein) together with N-WASP (neural Wiskott-Aldrich
syndrome protein) regulates actin polymerization that is crucial for invadopodia
and filopodia formation. Recently, we reported the WIP interaction with ITSN1
which is highly implicated in endo-/exocytosis, apoptosis, mitogenic signaling
and cytoskeleton rearrangements. Here we demonstrate that the WIP/ITSN1 complex
is involved in the transferrin receptor recycling and partially co-localizes with
a marker of the fast recycling endosomes, RAB4. Moreover, ITSN1 recruits WIP to
RAB4-positive vesicles upon overexpression. Our data indicate that WIP enhances
the interaction of N-WASP with ITSN1 and promotes ITSN1/beta-actin association.
Moreover, the WIP/ITSN1-L complex facilitates formation of filopodia-like
protrusions in MCF-7 cells. Thus, WIP/ITSN1 complex is involved in the cellular
vesicle trafficking and actin-dependent membrane processes.
PMID- 29958949
TI - Human Leukocyte Antigen class II polymorphisms among Croatian patients with type
1 diabetes and autoimmune polyglandular syndrome type 3 variant.
AB - This study included 161 patients: 92 patients had type 1 diabetes (T1D) while 69
patients had a combination of T1D and autoimmune thyroiditis, the so-called
autoimmune polyglandular syndrome type 3 variant (APS3v). Those patients, as well
as 93 controls, were typed for HLA-DRB1 and -DQB1 genes to assess their possible
contribution to the development/protection of T1D with/without autoimmune
thyroiditis. Both HLA-DRB1*04 and -DRB1*03 frequencies were significantly higher
among T1D and APS3v patients than in controls. The frequencies of HLA-DRB1*11 and
-DRB1*15 were lower among T1D patients, while HLA-DRB1*07 and -DRB1*11 occurred
significantly less frequently among APS3v patients in comparison to controls. HLA
DQB1*03:01 and -DQB1*03:02 were associated with a higher risk of developing T1D
and APS3v; HLA-DQB1*02 was significantly more present among APS3v patients while
HLA-DQB1*03:03 was observed with a significantly lower frequency only among T1D
patients. HLA-DRB1*03~DQB1*02 and HLA-DRB1*04~DQB1*03:02 were associated with
both diseases. The higher frequency of HLA-DRB1*03/DRB1*03 among APS3v patients
was the only significant difference in genotype frequency when compared to T1D
patients, while high risk (HLA-DRB1*03/DRB1*04) and medium risk genotypes for T1D
(HLA-DRB1*04/DRB1*04) occurred with similar frequencies in both patient groups.
Although some of the results point toward shared genetic susceptibility of T1D
and APS3v, observed differences in both susceptible/protective HLA profiles
indicate the necessity of further studies in order to elucidate the pathogenesis
of these diseases.
PMID- 29958950
TI - Transcriptome signature of liver tissue with divergent mutton odour and flavour
using RNA deep sequencing.
AB - Mutton consumption is less popular in many Asian countries including Indonesia,
whose consumers often complain about the unpleasant flavour and odour of the
meat. The main causes of mutton odour are the two compounds of branched chain
fatty acid (BCFA): methylnonanoic (MNA), phenol, 3-methyl (MP), 4-methylnonanoic
(MNA) and 4-ethyloctanoic (EOA) present in all the adipose tissue; and the 3
methylindole (MI) or skatole and indole, which are originated from pastoral
diets. It is crucial to understand the genetic mechanism of mutton odour and
flavour (MOF) to select sheep for lower BCFA and indole thus reduce the
unpleasant flavour of meat. The aim of the present study was to investigate
transcriptome profiling in liver tissue with divergent MOF using RNA deep
sequencing. Liver tissues from higher (n = 3) and lower (n = 3) MOF sheep were
analysed using Illumina HiSeq 2500. The total number of reads produced for each
liver sample ranged from 21.37 to 25.37 million. Approximately 103 genes were
differentially expressed (DEGs) with significance level of p-adjusted value
<0.05. Among them, 60 genes were up-regulated, and 43 were down-regulated (p <
0.01, FC > 1.5) in higher MOF group. Differentially regulated genes in high MOF
liver samples were enriched in biological processes such as cellular response to
chemical stimulus and endogenous stimulus; cellular components such as such as
basement membrane and extracellular matrix; and molecular functions such as haeme
binding and oxidoreductase activity. Among the DEGs, metabolic phase I related
genes belonging to the cytochrome P450 CYP2A6 were dominantly expressed.
Additionally, phase II conjugation genes including UDP glucuronosyltransferases
UGT2B18, sulfotransferase SULT1C1, and glutathione S-transferase GSTM1 were
identified. The dominant candidate genes for SOF could be cytochrome P450, sodium
channel protein, transmembrane protein, glutathione transferase, UDP
glucuronosyltransferases and sulfotransferase. Pathway analysis identified
steroid hormone biosynthesis and chemical carcinogenesis by cytochrome P450
pathways which may play important roles in MOF-related molecules metabolism. This
work highlighted potential genes and gene-networks that may affect meat off
flavour and odour in sheep.
PMID- 29958951
TI - Molecular cloning of androgen receptor and gene expression of sex steroid hormone
receptors in the brain of newborn Chinese alligator (Alligator sinensis).
AB - Sex steroid hormones play an important role in mediating physiological responses
and developmental processes through their receptors across all vertebrates.
Chinese alligator (Alligator sinensis) is a critically endangered reptile species
unique to China. In this study, we have cloned one of the sex steroid hormone
receptor genes, androgen receptor (AR) from the brain of Chinese alligator for
the first time. The full-length AR cDNA is 2717 bp in length with an open reading
frame (ORF) encoding 722 amino acids. Amino acid alignment analyses indicated
that the ARs exhibit highly conserved functional domains. Especially, the P-box
and D-box, which are essential to ensure that receptor binding to the androgen
response elements, are completely conserved in selected species. Using the
quantitative real-time PCR (qPCR), the spatial expression of four receptor mRNAs
in all newborn brain tissues and temporal expression of them in the cerebrum
during the embryonic development in Chinese alligators were investigated. The
results of qPCR showed ubiquitous expression of the four receptor mRNAs in all
newborn brain tissues examined and significant changes in the expression levels
of these receptor mRNAs in the embryonic development. These results suggest that
sex steroid hormones might play an important role in the regulation of complex
neuroendocrine activities in newborn Chinese alligator. Furthermore, these data
provide an important foundation for further studies on endocrinology and
molecular biology of non-mammalian sex steroid hormone receptors.
PMID- 29958952
TI - Association and in silico studies of ENPP1 gene variants with type 2 diabetes
mellitus in a Northern Iranian population.
AB - In the current study, a sample population of Northern Iranians was selected to
investigate the association of K121Q, rs1799774, rs7754561, and rs997509 ENPP1
gene variants and their haplotypes with T2DM. Genomic DNAs of 978 samples were
extracted by Salting Out standard technique and then genotyped by the TaqMan
assay. The results show significant differences between study groups for K121Q (p
= 0.0004) under a Dominant and rs7754561 (p = 0.002) under a co-dominant
hereditary model. Based on allele frequency, there was a significant difference
between two study groups at K121Q and rs7754561 variants (p = 0.010 and p = 0.01,
respectively). There was no evidence for an association between ENPP1 haplotypes
and overall risk of T2DM. Genotype-phenotype sub-analyses showed no significant
relationship of four studied polymorphisms with age, gender, FBS, and systolic
and diastolic blood pressures. Homology modeling and molecular docking of ENPP1
in K173 and Q173 models with ATP, AMP, and 2'3'-cGAMP as ligands revealed that
all ligands had a more binding affinity to Lys173 protein model, and 2'3'-cGAMP
had a higher affinity to both ENPP1 protein models compared to ATP and AMP. These
findings suggest that ENPP1 gene variants may have a potential impact on the
occurrence of T2DM in Northern Iranians.
PMID- 29958953
TI - Deciphering the role of IspD (2-C-methyl-D-erythritol 4-phosphate
cytidyltransferase) enzyme as a potential therapeutic drug target against
Plasmodium vivax.
AB - Biosynthesis of isoprenoids (MEP Pathway) in apicoplast has an important role
during the erythrocytic stages of Plasmodium, as it is the sole pathway to
provide the major isoprene units required as metabolic precursor for various
housekeeping activities. With the intensifying need to identify a novel
therapeutic drug target against Plasmodium, the MEP pathway and its components
are considered as potential therapeutic targets, due to the difference in the
isoprenoid synthesis route (MVA) functional in the host cells. While few major
components have already been studied from this pathway for their potential as a
drug target, IspD (2-C-methyl-D-erythritol-4-phosphate cytidyltransferase)
enzyme, the enzyme catalyzing the third step of the pathway has only been tested
against a synthetic compound from Malaria box called MMV008138, which also has
not shown adequate inhibitory activity against P. vivax IspD. In the present
study, to validate the potential of PvIspD as a drug target, various
antimicrobial agents were screened for their inhibition possibilities, using in
vitro High Throughput Screening (HTS) technique. Shortlisted antimicrobial drug
molecules like Cefepime, Tunicamycin and Rifampicin were further validated by in
vitro biochemical enzyme inhibition assays where they showed activity at
nanomolar concentrations suggesting them or their derivatives as prospective
future antimalarials. This study also confirmed the in-vivo expression of PvIspD
protein during asexual stages by sub-cellular localization in apicoplast and
explores the importance of the IspD enzyme in the development of new
therapeutics.
PMID- 29958954
TI - MiR-532-5p alleviates hypoxia-induced cardiomyocyte apoptosis by targeting PDCD4.
AB - MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs involved in
regulating various biological processes at the post-transcription level.
Accumulating evidence suggests that hypoxia caused by acute myocardial infarction
induces cardiomyocyte damage including apoptosis. Previous studies regarding the
miRNAome in H9c2 cells under hypoxia have shown that hypoxia modulates miRNA
expression in H9c2 cells, including miR-532-5p. We therefore investigated whether
miR-532-5p has a potential function in the cardiomyocyte response to hypoxia. In
the present study, we found that miR-532-5p, which was down-regulated in hypoxia
exposed H9c2 cells and the myocardium of acute myocardial infarction rats,
alleviated hypoxia-induced H9c2 cell apoptosis. Additionally, we identified PDCD4
as the direct target of miR-532-5p, which partly elucidates the anti-apoptotic
mechanism of miR-532-5p. In summary, this study revealed that miR-532-5p has
cardioprotective effects against hypoxia-induced apoptosis in H9c2 cells.
PMID- 29958955
TI - Identification and analysis of the chloride channel gene family members in
tobacco (Nicotiana tabacum).
AB - The chloride channel (CLC) protein family, which includes both chloride (Cl-)
channels and chloride/proton (Cl-/H+) antiporters, is present in all domains of
life, from prokaryotes to eukaryotes. However, there are no reported studies
about this gene family in tobacco, an economically important global crop plant.
In this study, we identified seventeen CLC genes in the genome of Nicotiana
tabacum. A multiple sequence alignment showed that all of the predicted proteins
shared a high sequence similarity and had a highly conserved GKxGPxxH motif. A
gene structure analysis revealed that the NtCLC genes had highly divergent intron
exon patterns. A phylogenetic and conserved motif analysis revealed that the
NtCLC family was divided into two clades, in a manner similar to other plants. We
also evaluated the expression patterns of these NtCLC genes in different tissues
and in plants treated with salt stress. The NtCLC genes had highly variable
expression patterns, for example, the largely stem- and bud-specific expression
patterns of NtCLC6 and NtCLC8, respectively. Salt stress treatment (300 mM NaCl)
induced the expression of NtCLC2, NtCLC3, and NtCLC12, suggesting that these
genes might play a role in tobacco responses to salt stress. Furthermore, the
concentration of Cl- in the NtCLC2- and NtCLC13-silenced plants showed an obvious
lower and higher level, respectively, than the control plants. Thus, we indicated
that NtCLC2 or NtCLC13 might play an important role in chloride transport or
metabolism in tobacco. Together, these findings establish an empirical foundation
for the further functional characterization of the NtCLC genes in tobacco.
PMID- 29958956
TI - Out-of-hospital cardiac arrest termination of resuscitation with ongoing CPR: An
observational study.
AB - INTRODUCTION: Termination of resuscitation guidelines for out-of-hospital cardiac
arrest can identify patients in whom continuing resuscitation has little chance
of success. This study examined the outcomes of patients transferred to hospital
with ongoing CPR. It assessed outcomes for those who would have met the universal
prehospital termination of resuscitation criteria (no shocks administered,
unwitnessed by emergency medical services, no return of spontaneous circulation).
METHODS: A retrospective cohort study of consecutive adult patients who were
transported to hospital with ongoing CPR was conducted at three hospitals in the
West Midlands, UK between September 2016 and November 2017. Patient
characteristics, interventions and response to treatment (ROSC, survival to
discharge) were identified. RESULTS: 227 (median age 69 years, 67.8% male)
patients were identified. 89 (39.2%) met the universal prehospital termination of
resuscitation criteria. Seven (3.1%) were identified with a potentially
reversible cause of cardiac arrest. After hospital arrival, patients received few
specialist interventions that were not available in the prehospital setting. Most
(n = 210, 92.5%) died in the emergency department. 17 were admitted (14 to
intensive care), of which 3 (1.3%) survived to hospital discharge. There were no
survivors (0%) in those who met the criteria for universal prehospital
termination of resuscitation. CONCLUSION: Overall survival amongst patients
transported to hospital with ongoing CPR was very poor. Application of the
universal prehospital termination of resuscitation rule, in patients without
obvious reversible causes of cardiac arrest, would have allowed resuscitation to
have been discontinued at the scene for 39.2% of patients who did not survive.
PMID- 29958957
TI - Quantitative assessment of pupillary light reflex for early prediction of
outcomes after out-of-hospital cardiac arrest: A multicentre prospective
observational study.
AB - AIM: To clarify whether quantitative assessment of pupillary light reflexes (PLR)
can predict the outcome of post-cardiac arrest (CA) patients during the first 72
h after the return of spontaneous circulation (ROSC). METHODS: Fifty adults
resuscitated after non-traumatic out-of-hospital CA (OHCA) (mean age 64.1 years
old, 36 males) were enrolled in four emergency hospitals. PLR was sequentially
measured at 0, 6, 12, 24, 48, and 72 h after ROSC by an automated portable
infrared pupillometry. PLR values for each time point were compared between both
survivors and non-survivors, and patients with either favourable (Cerebral
Performance Category (CPC) 1 or 2) or unfavourable neurological outcomes.
RESULTS: Twenty-three patients survived for 90 days after CA, and 13 patients
achieved favourable neurological outcomes. The PLR values of the survivors and
patients with favourable neurological outcomes were consistently greater than
those of non-survivors (P < 0.001) and those with unfavourable neurological
outcomes (P < 0.001), respectively. The change in PLR over time was not
statistically different between the outcome groups. The 0-hour PLR best predicted
both 90-day survival (AUC = 0.82, cutoff 3%, sensitivity 0.87, specificity 0.80)
and favourable neurological outcomes (AUC = 0.84, cutoff 6%, sensitivity 0.92,
specificity 0.74). No patient with a 6-hour PLR less than 3% survived for 90 days
after CA. CONCLUSIONS: Quantitatively measured PLR was consistently greater in
survivors and patients with favourable neurological outcomes during the 72 h
after ROSC. Quantitative assessment of PLR at as early as 0 h has a potential
role for prognostication in post-CA patients.
PMID- 29958958
TI - Outcomes and healthcare-associated costs one year after intensive care-treated
cardiac arrest.
AB - BACKGROUND: Despite the significant socioeconomic burden associated with cardiac
arrest (CA), data on CA patients' long-term outcome and healthcare-associated
costs are limited. The aim of this study was to determine one-year survival,
neurological outcome and healthcare-associated costs for ICU-treated CA patients.
METHODS: This is a single-centre retrospective study on adult CA patients treated
in Finnish tertiary hospital's ICUs between 2005 and 2013. Patients' personal
identification number was used to crosslink data between several nationwide
databases in order to obtain data on one-year survival, neurological outcome, and
healthcare-associated costs. Healthcare-associated costs were calculated for
every patient stratified by cardiac arrest location (OHCA = out-of-hospital
cardiac arrest, IHCA = all in-hospital cardiac arrest, ICU-CA = in-ICU cardiac
arrest) and initial cardiac rhythm. Cost-effectiveness was estimated by dividing
total healthcare-associated costs for all patients from the respective group by
the number of survivors and survivors with favourable neurological outcome.
RESULTS: The study population included 1,024 ICU-treated CA patients. The sum of
costs for all patients was ?50,847,540. At one-year after CA, 58% of OHCAs, 44%
of IHCAs, and 39% of ICU-CAs were alive. Of one-year survivors 97% of OHCAs, 88%
of IHCAs, and 93% of ICU-CAs had favourable neurological outcome. Effective cost
per one-year survivor was ?76,212 for OHCAs, ?144,168 for IHCAs, and ?239,468 for
ICU-CAs. Effective cost per one-year survivor with favourable neurological
outcome was ?81,196 for OHCAs, ?164,442 for IHCAs, and ?257,207 for ICU-CAs.
CONCLUSIONS: In-ICU CA patients had the lowest one-year survival with the
effective cost per survivor three times higher than for OHCAs.
PMID- 29958959
TI - Lycium europaeum Linn as a source of polysaccharide with in vitro antioxidant
activities and in vivo anti-inflammatory and hepato-nephroprotective potentials.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lycium europaeum Linn. is widely used to treat
the burning of the skin and well-known as a medicinal plant having various
biological activities. AIMS OF THE STUDY: The purpose of the present study is to
characterize the polysaccharide from L. europaeum L. leaves (LEP) and to explore
its antioxidant, anti-inflammatory and hepato-nephroprotective properties.
MATERIALS AND METHODS: The structural and functional characteristics of LEP were
investigated using X-ray diffraction techniques (XRD), Scanning Electron
Microscopy (SEM), and FT-IR Spectroscopy. The antioxidant activity was evaluated
using 2,2-diphenyl-1-picrylhydrazyl and hydrogen peroxide scavenging assays.
Hepato-renal effects were studied using CCl4 and cisplatin-induced liver and
kidney injuries in mice, respectively. Anti-inflammatory activity was assessed on
carrageenan-induced paw edema. RESULTS: The LEP showed an interesting water
holding capacity and effective foaming and emulsifying properties. XRD analysis
suggested that LEP form a semi-crystalline polymer with an amorphous structure.
FT-IR profile showed the presence of pyranose ring in LEP. SEM and helix-coil
transition analyses indicated that LEP had a lamellar structure with angular
edges and didn't present a triple helical conformation in solution. In vitro, LEP
indicated significant concentration-dependent antioxidant activity. In vivo, LEP
treatment significantly reduced the effects of CCl4 intoxication on serum liver
biomarkers (AST, ALT, LDH, and GGT) and the effect of cisplatin on serum renal
biomarkers (urea, blood urea nitrogen, creatinine, and uric acid). Meanwhile, LEP
diminishes significantly the effect of CCl4 and cisplatin on the level of lipid
peroxidation in liver and kidney tissues, respectively. Additionally, the normal
histological structure of liver and kidney was restored after treatment with the
polysaccharide. LEP possessed a significant anti-inflammatory activity on acute
inflammation induced by carrageenan in mice. CONCLUSION: Overall, the findings of
this study support the traditional use of L. europaeum L. This plant may also be
used as a good agent for protection against inflammatory diseases and hepato
renal injuries in patients with cancer.
PMID- 29958960
TI - The polyherbal drug GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra
sinica inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced
obese mice.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: The herbal composition Gyeongshingangjeehwan 18
(GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch
(Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an
antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally
been reported to inhibit obesity and related metabolic diseases such as insulin
resistance and dyslipidemia. OBJECTIVE: This study investigated the effects of
GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet
(HFD) and the underlying cellular and molecular mechanisms involved. METHODS:
C57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD
supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13
weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were
performed to assess NAFLD development in these mice. RESULTS: Mice fed an HFD had
increases in body weight, epididymal adipose tissue mass, adipocyte size, and
adipose expression of inflammation-related genes compared with those fed an LFD.
These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18
without affecting food consumption profiles. GGEx18 not only decreased serum
levels of triglycerides, free fatty acids, and alanine aminotransferase, but also
decreased hepatic lipid accumulation, numbers of mast cells and alpha-smooth
muscle actin-positive cells, and collagen levels induced by an HFD. Consistent
with the histological data, the hepatic expression of lipogenesis-, inflammation
, and fibrosis-related genes was lower, while hepatic fatty acid beta-oxidation
related gene expression was higher, in mice receiving GGEx18 compared to mice fed
only the HFD. DISCUSSION AND CONCLUSION: These results indicate that GGEx18
attenuates visceral obesity and NAFLD, in part by altering the expression of
genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese
mice. These findings suggest that GGEx18 may be effective for preventing and
treating NAFLD associated with visceral obesity.
PMID- 29958961
TI - Maternal stress during pregnancy induces depressive-like behavior only in female
offspring and correlates to their hippocampal Avp and Oxt receptor expression.
AB - The majority of studies examining the consequences of prenatal stress in rodent
models analyze pups having been raised by their biological mother, i.e. the
female which experienced stress during her pregnancy. To test whether pregnancy
stress changes maternal behavior and thereby - in addition to stress exposure in
utero - influences behavior and brain function of offspring, we implemented a
fostering model, in which mouse pups that were not stressed in utero, are raised
by dams which were exposed to stress during their pregnancy. We found that dams,
which were stressed during pregnancy (PS foster dams), unexpectedly displayed
slightly more active and passive light time nursing compared to unstressed dams
(CON foster dams). Adult male offspring which were raised by a PS foster dam
showed significantly less anxiety-like behavior compared to males raised by a CON
foster dam, whereas adult female offspring which were raised by PS foster dams
displayed increased depressive-like behavior as a tendency. Since the arginine
vasopressin receptor 1a (AvpR1a) and the structurally related oxytocin receptor
(OxtR) are both closely related to stress-responsiveness, anxiety and depression,
mRNA expression of these genes were assessed in the hippocampus of adult male and
female offspring. No significant differences in mRNA expression of both receptor
types were observed, however, in female offspring of PS foster dams maternal
licking/grooming correlated positively with AvpR1a and negatively with OxtR mRNA
expression. These findings indicate that stress during pregnancy does not reduce,
but slightly increase maternal behavior, which might lead to sex-specific
behavioral outcomes and changes in hippocampal AvpR1a and OxtR mRNA expression in
adult offspring.
PMID- 29958962
TI - Searching for auditory targets in external space and in working memory:
Electrophysiological mechanisms underlying perceptual and retroactive spatial
attention.
AB - Attention can be shifted within internal representations maintained in working
memory. These retroactive processes are particularly inherent to the processing
of auditory information that is especially transient over time and thus, requires
us to continuously maintain, attend to, and integrate information in working
memory. Using EEG recordings, the present study investigated the
neurophysiological mechanisms underlying selective spatial attention in a
retroactive as opposed to a perceptual auditory search task. Two kinds of sound
stimuli were employed: a horizontal sound array consisting of two natural sounds
presented simultaneously in the left and right hemispace and a central single
target sound. The target sound was provided either after (retroactive search) or
before the presentation of the sound array (perceptual search). In both search
conditions, participants completed a sound localization and a sound detection
task, indicating the position (left or right) or the presence versus absence (yes
or no) of a particular target sound. Analyses revealed a lateralization of alpha
power oscillations (8-12 Hz) over parieto-occipital scalp in both perceptual and
retroactive sound localization tasks, but not in respective sound detection
tasks, suggesting auditory alpha lateralization to be restricted to spatially
specific task demands. The observed asymmetric modulations of alpha power in
sound localization are consistent with analogous findings from the visual domain,
supporting the supramodal role of alpha oscillations in the deployment of spatial
attention. Hence, we conclude that auditory alpha lateralization is a higher
order attention mechanism that operates in perceptual and mnemonic space
reflecting the access to a spatially-specific, supramodal response template.
PMID- 29958963
TI - Adding electrical stimulation during standard rehabilitation after stroke to
improve motor function. A systematic review and meta-analysis.
AB - BACKGROUND: Clinical studies have shown that sensory input improves motor
function when added to active training after neurological injuries in the spinal
cord. OBJECTIVE: We aimed to determine the effect on motor function of
extremities of adding an electrical sensory modality without motor recruitment
before or with routine rehabilitation for hemiparesis after stroke by a
comprehensive systematic review and meta-analysis. METHODS: We searched databases
including MEDLINE via PubMed and the Cochrane Central Register of Controlled
Trials from 1978 to the end of November 2017 for reports of randomized controlled
trials or controlled studies of patients with a clinical diagnosis of stroke who
underwent 1) transcutaneous electrical nerve stimulation (TENS) or peripheral
electromyography-triggered sensory stimulation over a peripheral nerve and
associated muscles or 2) acupuncture to areas that produced sensory effects,
without motor recruitment, along with routine rehabilitation. Outcome measures
were motor impairment, activity, and participation outcomes defined by the
International Classification of Functioning, Disability and Health. RESULTS: The
search yielded 11studies with data that could be included in a meta-analysis.
Electrical sensory inputs, when paired with routine therapy, improved peak torque
dorsiflexion (mean difference [MD] 2.44 Nm, 95% confidence interval [CI] 0.26
4.63). On subgroup analysis, the combined therapy yielded a significant
difference in terms of sensory stimulation without motor recruitment only on the
Timed Up and Go test in the chronic phase of stroke (MD 3.51sec, 95% CI 3.05
3.98). The spasticity score was reduced but not significantly (MD-0.83 points,
95% CI -1.77-0.10). CONCLUSION: Electrical sensory input can contribute to
routine rehabilitation to improve early post-stroke lower-extremity impairment
and late motor function, with no change in spasticity. Prolonged periods of
sensory stimulation such as TENS combined with activity can have beneficial
effects on impairment and function after stroke.
PMID- 29958964
TI - Lynch Syndrome-associated Upper Tract Urothelial Carcinoma.
PMID- 29958965
TI - Improved Detection of Clinically Significant Prostate Cancer With Software
assisted Systematic Biopsy Using MR/US Fusion in Patients With Negative Prostate
MRI.
AB - OBJECTIVE: To compare detection rates of clinically significant prostate cancer
(Gleason 7 or above) between standard transrectal ultrasound guided biopsy
(TRUSGB) and software-assisted systematic biopsy (SASB) using magnetic
resonance/ultrasound fusion in the setting of negative multiparametric magnetic
resonance imaging (mpMRI) in biopsy-naive patients. METHODS: We reviewed our
prospectively maintained database of consecutive men that underwent prostate
biopsy following mpMRI from September 2015 to December 2016. Patients with no
prior biopsy (ie, biopsy naive) whose mpMRI demonstrated no targetable lesions
were included. Patients underwent either TRUSGB (n = 23) or SASB (n = 29). SASB
was performing using the MRI/US fusion systematic template. Prebiopsy data were
collected, and the detection rate of clinically significant prostate cancer was
compared between biopsy approaches. RESULTS: Baseline patient characteristics
were similar between the TRUSGB and SASB groups. Clinically significant prostate
cancer was found in no patients undergoing TRUSGB and in 6 patients undergoing
SASB (0 vs 21%, P = .028). CONCLUSION: Based on our institutional experience,
SASB is associated with a higher detection rate of clinically significant
prostate cancer when compared to TRUSGB for biopsy-naive patients with negative
prostate mpMRI. Software co-registration of the MRI and ultrasound image may
optimize the distribution of biopsy cores allowing for improved prostate cancer
detection compared to conventional TRUSGB.
PMID- 29958966
TI - Dextrose Instillation as an Alternative Agent to Observe Ureteral Efflux During
Pelvic Reconstructive Surgery.
AB - OBJECTIVE: To evaluate the use, cost, postoperative urinary tract infection (UTI)
rates, and complications of dextrose instillation during cystoscopy. METHODS: The
medical records of patients who underwent cystoscopy during pelvic reconstructive
surgery between June 2016 and June 2017 were reviewed. Patients were divided into
two groups: patients who had one ampule of dextrose 50% (D50) directly instilled
and patients who did not have D50 instilled during cystoscopy. Preoperative
demographics, UTI rates, and postoperative complications were compared.
Pharmaceutical cost and availability were reported by the pharmacy at our
institution. RESULTS: Out of 63 patients identified, dextrose instillation was
used in 20 patients and no dextrose was used in 43 patients. Each ampule of D50
cost $2.18 and there were no problems with supply shortage. As D50 was directly
instilled into the bladder, there was immediate visualization of ureteral efflux
at the time of surgery. Three patients (15%) in the dextrose group and 10
patients (23%) in the nondextrose group developed postoperative UTIs. There was
no statistically significant difference in postoperative UTI rates between the
two groups (p = 0.43) and there were no differences in postoperative
complications. CONCLUSION: Dextrose is a safe, cost-effective, readily available
agent that provides instantaneous visualization of ureteral efflux without an
increased risk of postoperative UTI.
PMID- 29958967
TI - Infrared Light Structured Sensor Three-dimensional Approach to Estimate Kidney
Volume: A Validation Study.
AB - OBJECTIVE: To validate a new procedure for the three-dimensional estimation of
total renal parenchyma volumeusing a structured-light infrared laser sensor.
METHODS: To evaluate the accuracy of the sensor for assessing renal volume, we
performed 3 experiments. Twenty freshly excised porcine kidneys were obtained.
Experiment A, the water displacement method was used to obtain a determination of
the renal parenchyma volume after immersing every kidney into 0.9% saline.
Thereafter a structured sensor (Occipital, San Francisco, CA) was used to scan
the kidney. Kidney sample surface was presented initially as a mesh and then
imported into MeshLab (Visual Computing Lab, Pisa, Italy) software to obtain the
surface volume. Experiment B, a partial excision of the kidney with measurement
of the excised volume and remnant was performed. Experiment C, a renorrhaphy of
the remnant kidney was performed then measured. Bias and limits of agreement
(LOA) were determined using the Bland-Altman method. Reliability was assessed
using the intraclass correlation coefficient (ICC). RESULTS: Experiment A, the
sensor bias was -1.95mL (LOA: -19.5 to 15.59, R2 = 0.410) with slightly
overestimating the volumes. Experiment B, remnant kidney after partial excision
and excised kidneyvolume were measured showing a sensor bias of -0.5mL (LOA -5.34
to 4.20, R2= 0.490) and -0.6mL (LOA: -1.97.08 to 0.77, R2 = 0.561), respectively.
Experiment C, the sensor bias was -0.89mL (LOA -12.9 to 11.1, R2= 0.888). ICC was
0.9998. CONCLUSION: The sensor is a reliable method for assessing total renal
volume with high levels of accuracy.
PMID- 29958968
TI - Adrenal Cyst in Pregnancy: A Surgical Emergency.
PMID- 29958969
TI - Reply by the Authors.
PMID- 29958970
TI - Hemorrhagic Cystitis Associated With Gefitinib Treatment: A Case Report.
PMID- 29958971
TI - Ileal Continent Reservoir: A Feasible Option for Bladder Augmentation and Urinary
Diversion.
AB - OBJECTIVE: To present the results of technique of continent urinary diversion,
described by Macedo, that allows the configuration of a tunnel with a flap of the
ileal tube at the same segment created for the reservoir. METHODS: From January
2006 to November 2016, 29 patients were underwent a urinary diversion by Macedo's
technique. Patients' demographics, hospitalization time, surgical time, follow
up, continence rate, reservoir capacity, and postoperative complications were
evaluated. RESULTS: Sixty-nine percent were male and the median age was 16.9
years. The main etiology was meningomyelocele (69.1%). The mean surgical time was
4.2 hours (standard deviation [SD] 0.9 range 2.9-6.3). The median length of
hospital stay was 10 days (interquartile range: 11.3 range 5-51). The mean follow
up was 3.3 years (SD 2.2 range 0.3-9.8). Procedure in the bladder neck was
performed in 12 patients (41.3%). A continence rate of the catheterizable conduit
was 82.8%.The reservoir capacity increased from 134.4 to 364.4 ml (P <.0001). The
continence rate improved significantly (20 vs 74%, P <.0001). There was no change
in glomerular filtration rates in the long term (143.1 vs 147, P = .45).
Morbidity rate was 58% (25 complications in 17 patients), 72% occurred within the
first 60 days and 60% were classified as Clavien-Dindo I or II. CONCLUSION:
Except for publications from the original author, this is the first series
described. The outcomes are similar, adding important data with respect to this
technique. They show that the ileal reservoir is feasible, reproducible, and with
good results.
PMID- 29958972
TI - Single-session Transvesical Laparoendoscopic 1-Port Removal of 2 Bladder
Diverticula in a Female Patient.
AB - BACKGROUND: Bladder diverticula are usually encountered in males, and they are a
rarity in women, especially in the absence of obstruction. Open surgery, as well
as laparoscopic or robotic, or single-port surgery have been applied successfully
to remove bladder diverticula.1-3 To the best of our knowledge, no single-port
diverticulectomies have been performed in women. OBJECTIVE: To present the case
of using the transvesical laparoendoscopic single-port surgery (T-LESS) for
excision of 2 bladder diverticula in a woman. MATERIALS: In August 2016, we
carried out the T-LESS access on a 67-year old woman to remove 2 symptomatic
bladder diverticula in 1 session. The patient was placed in the lithotomy
position and was under general anesthesia. The procedure was performed
transvesically (percutaneous intraluminal approach) with a single-port device
(Tri-Port+) via a 1.5-cm incision made 3 cm above the pubic symphysis. Standard
10-mm optic and straight laparoscopic instruments were used. The diverticula were
dissected and removed from the bladder with a combination of standard
laparoscopic and endoscopic instruments introduced through the TriPort+ or the
urethra. The bladder wall openings were closed by running absorbable 2/0
polyglactin sutures. An 18F Foley catheter was left in place for 6 days. RESULTS:
The operation lasted 120 minutes. Blood loss was minimal, and no complications
were observed. The postoperative period was uneventful. The patient was
discharged within 19 hours of surgery. During a 9-month follow-up, the patient
reported the significant improvement in the severity of symptoms. Laboratory
examination results were all within the normal range. CONCLUSION: The T-LESS
procedure can be considered as a valuable option for diverticulectomies in female
patients because of its minimal invasiveness, short hospital stay, and fast
recovery time.
PMID- 29958973
TI - A 12-Month Follow-up After a Single Intracavernous Injection of Autologous
Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction
Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial.
AB - OBJECTIVE: To explore safety in adipose-derived regenerative cells (ADRC)
therapy, treating erectile dysfunction (ED). METHODS: Twenty-one patients with ED
after radical prostatectomy, with no signs of recovery using conventional
therapy, received a single intracavernous injection of autologous ADRC and were
followed for 1 year. Six men were incontinent, and 15 were continent at
inclusion. The primary (safety of ADRC therapy) and secondary endpoints (sexual
function) were evaluated at 1, 3, 6, and 12 months after ADRC injection by
registration of adverse events and validated questionnaires using the
international index of erectile function-5 and erection hardness score. RESULTS:
No serious adverse events occurred, but 8 reversible minor events related to the
liposuction were noted. Eight out of 15 (53%) patients in the continent group
reported erectile function sufficient for intercourse at 12 months. Baseline
median international index of erectile function-5 scores (6.0; interquartile
range [IQR] 3) were unchanged 1 month after the treatment, but significantly
increased after 6 to 7 (IQR 17). This effect was sustained at 12 months (median
8; IQR 14). We did not see any improvements in erectile function in the group of
incontinent men or among men with ED prior to radical prostatectomy. CONCLUSION:
Intracavernous injection of ADRC is safe in this phase 1 study with a 12-month
follow-up.
PMID- 29958974
TI - Enhanced delivery of naproxen to the viable epidermis from an activated poly N
isopropylacrylamide (PNIPAM) Nanogel: Skin penetration, modulation of COX-2
expression and rat paw oedema.
AB - Stimulus-responsive drug-loaded poly (N-isopropylacrylamide) nanogels were
examined as a means of enhancing the delivery of naproxen into skin ex vivo.
Following massaging into skin, the epidermis was probed (with and without base
activation) for depth penetration and transdermal delivery of drug, and anti
inflammatory activity in the relative levels of COX-2 expression. Rat paw oedema
testing was used to determine anti-inflammatory effects in vivo. When activated
by sodium carbonate, particle size reduced by 19%. Tape stripping revealed
significantly greater delivery of naproxen into the epidermis for the activated
nanogel and the steady state flux was enhanced 2.8-fold. With base-activation COX
2 was 50% lower than non-activated, and this trend was confirmed by
immunostaining, and by the reduction of rat paw swelling which provided ex vivo -
in vivo corroboration. A mechanism of action is proposed. In conclusion, stimulus
responsive nanogels have potential for enhancing dermal drug delivery and
therapeutic outcomes in inflammatory skin diseases.
PMID- 29958975
TI - First report of extensively-drug-resistant Proteus mirabilis isolate carrying
plasmid-mediated blaNDM-1 in a Tunisian intensive care unit.
AB - Emergence of the New Delhi metallo-beta-lactamase (NDM-1), an Ambler class B
metallo-beta-lactamase able to hydrolyse all beta-lactams except monobactams,
constitutes a critical and increasingly important medical issue. The acquisition
of blaNDM-1 is of particular concern for Proteus mirabilis, which is
intrinsically resistant to tetracycline, tigecycline and colistin, as this will
make clinical treatment extremely difficult. To the authors' knowledge, this is
the first report of the blaNDM-1 gene in an extensively-drug-resistant P.
mirabilis clinical isolate carrying plasmid-mediated resistance to carbapenems
(blaNDM-1), cephalosporins (blaCMY-4), aminoglycosides (aph3 VIa and aph3 Ia) and
fluoroquinolones (qnrA6).
PMID- 29958976
TI - Fosfomycin Etest for Enterobacteriaceae: Interobserver and interlaboratory
agreement.
AB - OBJECTIVES: The increasing use of fosfomycin requires reliable susceptibility
testing in clinical practice. The reference standard, agar dilution (AD), is
rarely used in routine settings. The fosfomycin Etest (BioMerieux) is frequently
used, although reading MICs can be hampered by the interpretation of the growth
of macrocolonies in the inhibition zone. We investigated the interobserver (IO),
interlaboratory (IL), and interobserver-interlaboratory (IOIL) agreement of the
fosfomycin Etest and evaluated the agreement with AD. METHODS: Etests were
performed for 57 extended spectrum beta-lactamase (ESBL)-producing
Enterobacteriaceae of four bacterial species (Escherichia coli, Klebsiella
pneumoniae, Klebsiella oxytoca and Enterobacter cloacae) in two laboratories.
Photographs of fosfomycin Etests were interpreted by four observers following
manufacturer's instructions. RESULTS: Essential agreement (EA) and categorical
agreement (CA) between Etest and AD were 57% and 89% (kappa-value 0.68),
respectively, with an underestimation of Etest interpretations compared with AD
of 0.26 (95% confidence interval [CI] 0.03-0.48) 2-fold dilutions. Between Etest
observations, IO-EA and -CA were reached in 82% and 94% of comparisons; IL-EA and
-CA in 38% and 85% of comparisons; and IOIL-EA and -CA in 40% and 85% of
comparisons, respectively. Agreement of the Etest with AD and between Etests was
better for E. coli than for other species. Ignoring all macrocolonies and haze
during Etest interpretation improved the agreement with AD (CA kappa-value 0.80)
and between Etests (CA kappa-value from 0.68 to 0.81). CONCLUSIONS: In this study
on 57 ESBL-producing Enterobacteriaceae, IOIL agreement was low with an EA of 40%
and a CA of 85%, affected most by IL agreement and to a lesser extent by IO
agreement.
PMID- 29958977
TI - Analysis of interventions against the liver fluke, opisthorchis viverrini.
AB - We adapt a population-based model of Opisthorchis viverrini transmission dynamics
to determine the effectiveness of three different interventions. The model
includes the definitive hosts, humans; the reservoir hosts, dogs and cats; and
the intermediate hosts, snails and fish. We consider the interventions: education
campaigns to reduce the consumption of raw or undercooked fish, improved
sanitation and treatment through mass drug administration. We fit model
parameters to a data set from two islands in southern Lao PDR. We calculate the
control reproduction number, simulate different scenarios and optimise the
interventions with optimal control. We look at the potential of the interventions
to eliminate transmission within 20 years. The model shows that education and
improved sanitation need a very high coverage to fulfil the goal of elimination,
whereas annual drug distribution at medium coverage is sufficient. The best
solution is a combination of drug distribution at a medium level of coverage and
as high as possible coverage of education and improved sanitation.
PMID- 29958978
TI - A model of vascular refilling with inflammation.
AB - Inflammation is prevalent in hemodialysis patients and is believed to
significantly contribute to cardiovascular disease progression in end stage renal
disease patients undergoing hemodialysis. Increased vascular permeability
associated with inflammation is likely to influence the capillary wall
properties, affecting vascular refilling during hemodialysis. In this paper, we
present a model that incorporates inflammation into a vascular refilling model.
We investigate how inflammation may affect the fluid volume and protein
concentration dynamics in the plasma and interstitial spaces. In our work, we
quantify inflammation by considering the concentration of the inflammatory
biomarker C-reactive protein (CRP). Traditional sensitivity functions and subset
selection based on asymptotic standard errors were used to aid in parameter
identification. Estimates of the parameters were calculated from numerically
generated measurements for fluid flux and hematocrit. Observations on the
capillary wall properties, filtration and reflection coefficients, were done
using data on mean CRP and serum albumin from a large population of European
hemodialysis patients in their terminal two years before death and patients
surviving for at least four years after dialysis initiation.
PMID- 29958979
TI - Circadian gene period1b regulates proinflammatory cytokine expression through NF
kappaB signalling in zebrafish.
AB - The circadian clock plays a critical role in regulating the immune system. Our
previous publication revealed that a mutation in the circadian gene period1b
(per1b) in zebrafish significantly decreased proinflammatory gene expression,
particularly under constant darkness (DD) conditions; however, the underlying
mechanisms remain unclear. In this study, using per1b-null mutant zebrafish and a
larval tail fin injury model, we observed that the loss of per1b resulted in the
downregulation expression of proinflammatory cytokines, such as IL-6 and TNF
alpha, at protein level. Furthermore, the loss of per1b downregulated ERK
phosphorylation and inhibited p65 phosphorylation, leading to reduced NF-kappaB
activation, which could downregulate the expression of proinflammatory cytokines,
such as IL-6 and TNF-alpha, in zebrafish. These results provided insight into the
communication between the circadian clock and immune functions.
PMID- 29958980
TI - Modulation of immune response and protective efficacy of recombinant outer
membrane protein F (rOmpF) of Aeromonas hydrophila in Labeo rohita.
AB - The outer-membrane proteins (OMPs) of Aeromonas hydrophila, an imperative fish
pathogen accountable for massive economic losses to aquaculture industry, are
found to be immunogenic and considered as potential vaccine candidates. In spite
of development in the formulation of vaccine candidates against Aeromonas
infection, no commercial preparation has been done so far; in addition, the
molecular mechanisms of immunoprotection induced by various vaccine formulations
in Indian major carp, Labeo rohita, are little known. The present study was
undertaken to evaluate the modulation of immunity and expression of immune
related genes post-rOmpF (recombinant outer-membrane protein of A. hydrophila, a
novel vaccine candidate) immunization and protective efficacy after A. hydrophila
challenge. The rOmpF-immunized fish showed a variable expression of the immune
related genes, viz. toll-like receptor 22 (TLR), complement component 3 (C3),
chemokine (CXCa), tumor necrosis factor-alpha (TNFalpha), interleukin 1beta (IL
1beta), manganese superoxide dismutase (MnSOD) and natural killer enhancing
factor (NKEF) in the head kidney tissues, when compared to the control group at
different time intervals post-vaccination. A significant increase in serum
hemolysin titer, ceruloplasmin level and myeloperoxidase activity was observed on
day 140 post immunization. Also, bacterial agglutination titer and antiprotease
activity were significantly increased on day 42 post immunization. No significant
change was observed in lysozyme activity. Challenge studies with live A.
hydrophila on day 140 post-immunization of L. rohita significantly increased the
relative percentage survival (~44%) in the vaccinated group. The results suggest
that the rOmpF could be used as a potential vaccine candidate to combat A.
hydrophila infection in fish.
PMID- 29958981
TI - Molecular systematics and phylogeography of the endemic Osgood's deermouse
Osgoodomys banderanus (Rodentia: Cricetidae) in the lowlands of western Mexico.
AB - Osgoodomys banderanus is a recognized and endemic rodent species of western
Mexico, an area known for its high biodiversity and number of endemisms.
Phylogeographical relationships within this taxon were analyzed based on
mitochondrial (ND3, tRNA-Arginine, ND4L and partial ND4) and nuclear (GHR)
nucleotide sequences. We obtained a total of 112 samples from 22 localities,
covering the complete distribution of the species. Phylogenetic analyses using
Maximum Likelihood and Bayesian inference confirmed that Osgoodomys is a
monophyletic group. In addition, phylogenetic and phylogeographic analyses
detected three major clades, which do not coincide with the recognized subspecies
of O. banderanus. The genetic lineages detected are the western clade (Nayarit,
Jalisco and northern Colima), the central clade (Colima, Michoacan, and northern
Guerrero) and the eastern clade (central and southern Guerrero). Genetic
distances among clades (5-9%) and nucleotide substitutions (30-88) among
haplogroups were high, especially in the southern group. Mountain ranges such as
the Transmexican Volcanic Belt and the Sierra Madre del Sur, as well as the
Balsas River act as geographical barriers for Osgoodomys. Our results suggest the
presence of three independent species, which need to be characterized
morphologically to confirm our hypothesis.
PMID- 29958982
TI - Comparative evolutionary and phylogenomic analysis of Avian avulaviruses 1-20.
AB - Avian avulaviruses (avulaviruses or AAvVs) infect a wide range of avian species
worldwide with variable clinical outcomes and economic impacts. Owing to broad
host spectrum, several novel avulaviruses are being reported from both wild and
domesticated birds that highlight the potential of the virus to evolve, adapt and
emerge in susceptible population. Pathobiological and phylogenetic
characterizations of individual avulaviruses are often demonstrated, however, a
cumulative and comparative assessment of avulaviruses remains elusive. To assess
evolutionary dynamics and potential emergence of novel avulaviruses, we enriched
existing databases of all known avulaviruses (specie-type 1-20), and determined
their genomics features based on both complete genomes and individual complete
genes. While a high nucleotide divergence (up to 65.4%) was observed among
avulaviruses, phylogenomic analysis revealed clustering of all avulaviruses into
three distinct clades. The major clade (Clade-I) included both oldest and newest
avulaviruses (2, 5, 6, 7, 8, 10, 11, 14, 15 and 20) and the second clade (Clade
II) consisted of avulaviruses 1, 9, 12, 13, 16, 17, 18 and 19, whereas the third
clade (Clade-III) carried only avulaviruses 3 and 4. Intriguingly, clustering
pattern was descriptive for individual gene-based analysis, however, the
hemagglutinin-neuraminidase (HN) and polymerase (L) genes showed clear and
discrete branching patterns similar to complete genome-based clustering.
Therefore, we propose the use of HN, or L genes or complete genome to study
epidemiological aspects of the avulaviruses. Genomic and residue characteristics
of all genes indicated a continuous evolution of the virus, and substitutions in
biologically important motifs warrant future investigations to assess their roles
in the pathobiology of the virus. Taken together, this comprehensive analysis of
all known avulaviruses ascertains continuous monitoring and surveillance of
wild/water-fowls and commercial poultry. These findings further our understanding
on the evolutionary dynamics and potential emergence of novel avulaviruses and
will establish bases to identify potential of wild-bird origin apathogenic
viruses to cause infections in commercial poultry.
PMID- 29958983
TI - Evolution of floral traits and impact of reproductive mode on diversification in
the phlox family (Polemoniaceae).
AB - Pollinator-mediated selection is a major driver of evolution in flowering plants,
contributing to the vast diversity of floral features. Despite long-standing
interest in floral variation and the evolution of pollination syndromes in
Polemoniaceae, the evolution of floral traits and known pollinators has not been
investigated in an explicit phylogenetic context. Here we explore
macroevolutionary patterns of both pollinator specificity and three floral traits
long considered important determinants of pollinator attraction across the most
comprehensive species-level phylogenetic tree yet produced for the family. The
presence of floral chlorophyll is reconstructed as the ancestral character state
of the family, even though the presence of floral anthocyanins is the most
prevalent floral pigment in extant taxa. Mean corolla length and width of the
opening of the floral tube are correlated, and both appear to vary with
pollinator type. The evolution of pollination systems appears labile, with
multiple gains and losses of selfing and conflicting implications for patterns of
diversification. Explicit testing of diversification models rejects the
hypothesis that selfing is an evolutionary dead-end. This study begins to
disentangle the individual components that comprise pollination syndromes and
lays the foundation for future work on the genetic mechanisms that control each
trait.
PMID- 29958984
TI - Bug Off - A website from experts at LSHTM and ARCTEC.
PMID- 29958985
TI - Time to recognize the positive impact and health benefits of mass gatherings.
PMID- 29958986
TI - Zika infection in pregnancy: Follow up and outcomes, where are all the data?
PMID- 29958987
TI - Prenatal caffeine ingestion induces long-term alterations in scavenger receptor
class B type I expression and glucocorticoid synthesis in adult male offspring
rat adrenals.
AB - Caffeine is contained within many drinks and food that are consumed daily.
Prenatal caffeine ingestion (PCI) is a risk factor for intrauterine growth
retardation (IUGR). We previously observed that PCI inhibits scavenger receptor
class B type I (SR-BI)-mediated cholesterol uptake in fetal adrenals,
subsequently decreasing glucocorticoid synthesis and inducing IUGR. In the
present study, we aimed to investigate the long-term effects of PCI on adrenal
glucocorticoid synthesis in adult male offspring rats. After establishing the PCI
induced IUGR, adult male offspring was injected intraperitoneally with 5 mg/kg.d
lipopolysaccharide (LPS) for 2 days to induce acute stress. We observed
persistent inhibition of SR-BI expression in PCI adrenals before and after
stress. Compared with the controls, the PCI offspring had higher corticosterone
concentrations after stress. The serum cholesterol concentration was stable
without intergroup differences before and after stress. The cholesterol
concentration in PCI adrenals showed a higher decrease rate than that of the
control after stress. In summary, PCI induced long-term alterations in SR-BI
expression and glucocorticoid synthesis in adult male offspring rat adrenals.
Cholesterol has to be over-consumed in PCI adrenals against acute stress. This
study provides an experimental basis to explain the susceptibility of IUGR
offspring to metabolic diseases in adults.
PMID- 29958988
TI - Residue analysis and dietary exposure risk assessment of tebufenozide in stem
lettuce (Lactuca sativa L. var. angustana Irish).
AB - Tebufenozide, a newly-developed nonsteroidal ecdysone agonist, is in pre
regulation phase (before approval for use) on stem lettuce in China. Aiming at
the safe application of tebufenozide, the dissipation and terminal residue trials
on stem lettuce were performed under good agricultural practice (GAP). The
dissipation trials shown that tebufenozide was rapidly degraded in stem lettuce,
with half-lives of 5.0-8.2 days. Pre-regulation dietary exposure risk assessments
were evaluated to recommend maximum residue limits (MRLs) based on risk quotients
(RQ) method. Relevant toxicological parameters including ADI (acceptable daily
intake) and ARfD (acute reference dose) were applied to assess the potential
dietary exposure risk. The results indicated the chronic dietary exposure risk
probability (RQc) of tebufenozide ranged from 36.4% to 70.0%. The acute dietary
exposure risk probability (RQa) of tebufenozide was 2.88%-8.49% in lettuce stems
and 14.0%-20.0% in lettuce leaves, respectively. On the basis of supervised field
trial data and dietary exposure risk assessment results, the MRLs of tebufenozide
were recommended as 3 mg/kg for lettuce stems and 10 mg/kg for lettuce leaves,
respectively. The results demonstrated that the dietary exposure risk of
tebufenozide used in stem lettuce under GAP was negligible and would not pose
unacceptable health risk to Chinese consumers.
PMID- 29958989
TI - Absence of adverse effects following administration of piperine in the diet of
Sprague-Dawley rats for 90 days.
AB - Piperine (E,E-) is a naturally occurring pungent and spicy constituent of black
pepperand is also used as an added flavoring ingredient to foods and beverages.
Piperine has been determined safe under conditions of intended use as a flavoring
substance by regulatory and scientific expert bodies. While concurring with the
Joint FAO/WHO Expert Committee on Food Additives (JECFA) and Flavor and Extract
Manufacturers Association (FEMA) Expert Panel on the safety of piperine, the
European Food Safety Authority (EFSA) requested additional toxicological data.
The results of a 90-day GLPcompliant dietary study, conducted in Sprague-Dawley
rats at target doses of 0, 5, 15, or 50 mg/kg bw/day, to respond to this request
are presented herein. No adverse effects were found attributable to ingestion of
piperine. Statistically significant changes in food consumption, body weight
gain, and plasma cholesterol levels were not considered adverse as discussed in
this paper. Therefore, the oral no-observed-adverse-effect level (NOAEL) was
determined to be the highest dose tested of 50 mg/kg bw/day. EFSA derived a lower
NOAEL of 5 mg/kg bw/day based on increased plasma cholesterol levels which still
affords an adequate margin of safety of over 48,000 and concluded that piperine
is not of safety concern.
PMID- 29958990
TI - Accelerated conversion of atrial fibrillation to normal sinus rhythm by pulmonary
delivery of flecainide acetate in a porcine model.
AB - BACKGROUND: Pulmonary delivery of antiarrhythmic agents has the potential to
increase rapidly targeted drug concentrations in pulmonary veins and left atrium
to terminate atrial fibrillation (AF). OBJECTIVE: We evaluated the efficacy of
flecainide administered via intratracheal instillation in terminating AF in a
reliable preclinical model. METHODS: In 11 closed-chest anesthetized Yorkshire
pigs, AF was induced by intrapericardial administration of acetylcholine (1 mL of
102.5 mM solution) followed by burst pacing and allowed to continue for 2 minutes
before intratracheal flecainide (0.4 or 0.75 mg/kg) administration. RESULTS: Both
the 0.4- and 0.75-mg/kg doses of intratracheal flecainide significantly reduced
AF duration by 35% (P = .02) and 54% (P = .001), respectively, compared to no
drug baseline. There was a strong inverse correlation (r2 = 0.87; P = .03)
between the duration of AF and the change in atrial depolarization duration in
response to intratracheal flecainide. Induction of AF resulted in a marked
increase in ventricular rate and corresponding reduction in mean arterial
pressure, which returned to baseline levels within 5 minutes after conversion.
CONCLUSION: Intratracheal flecainide instillation is effective in rapidly
converting AF to normal sinus rhythm and restoring mean arterial pressure and
heart rate to baseline values. The basis for this efficacy is likely rapid
absorption of the drug through the lungs and delivery as a first-pass bolus to
the left atrial and ventricular chambers and then to the coronary arterial
circulation. The anti-AF effect of flecainide is inversely correlated with the
drug's prolongation of atrial depolarization, implicating slowing of intra-atrial
conduction as an important mechanism underlying conversion of AF to normal sinus
rhythm.
PMID- 29958991
TI - Delivery systems of local anesthetics in bone surgery: are they efficient and
safe?
AB - Management of postoperative pain following bone surgery includes administration
of local anesthetics (LAs). Smart delivery systems, including triggered systems,
have been designed to provide a continuous release of LA in situ. However, these
systems can provide a high level of LA locally. This review will examine the
state-of-the-art regarding the LA delivery systems optimized for management of
postoperative pain in bone surgery and will discuss the potential adverse effects
of LAs on the overall pathways of bone healing, including the inflammation
response phase, hemostasis phase, tissue repair phase and remodeling phase. There
is a clinical need to document these effects and the potential impacts on the
clinical outcome of the patient.
PMID- 29958992
TI - MiR-429 regulates rat liver regeneration and hepatocyte proliferation by
targeting JUN/MYC/BCL2/CCND1 signaling pathway.
AB - Increasing evidence indicates that miR-429 is involved in tumor suppression in
various human cancers. However, its role in liver regeneration remains
unexplored. Liver regeneration is a highly orchestrated process that can be
regulated by microRNAs (miRNAs), although the mechanisms are largely unclear. In
this study, we aimed to identify the role of miR-429 in hepatocyte proliferation
during liver regeneration. First, we performed microarray analysis and qRT-PCR.
Results indicated that miR-429 level in rat liver markedly decreased 30 h after
partial hepatectomy, and miR-429 overexpression disrupted BRL-3A proliferation
and the transition of G1 to S phase in rat hepatocyte and promoted hepatocyte
apoptosis. By contrast, miR-429 down-regulation had inverse effects. MiR-429
negatively regulated JUN expression in vitro and in vivo. After using JUN siRNA,
we found that JUN inhibition mediates the effect of miR-429 in hepatocyte
proliferation and growth and miR-429 negatively regulates JUN/MYC/BCL2/CCND1
signaling pathways. Our results also indicated that miR-429 inhibits hepatocyte
proliferation and liver regeneration by targeting JUN/MYC/BCL2/CCND1.
PMID- 29958993
TI - HRD1-mediated PTEN degradation promotes cell proliferation and hepatocellular
carcinoma progression.
AB - The tyrosine phosphatases family member PTEN is a tumor suppressor which is
widely expressed throughout the body and is involved in a variety of biological
functions. PTEN is known to be frequently mutated or downregulated in human
cancers. However, the underlying molecular mechanism remains largely unknown.
Here, using a proteomic approach, we identified the E3 ubiquitin ligase HRD1,
which was previously reported to be involved in endoplasmic reticulum associated
degradation (ERAD), as one of the PTEN-interacting proteins. We also found that
HRD1 promoted PTEN degradation by positively regulating its ubiquitination. In
addition, suppression of HRD1 expression resulted in the inhibition of the
growth, migration and invasion of hepatocellular carcinoma in vitro and in vivo.
Finally, we detected a negative correlation between HRD1 and PTEN expression in
human hepatocellular carcinoma. From these results we propose a novel molecular
mechanism of HRD1 to promote hepatocellular tumorigenesis via PTEN inactivation.
We conclude that targeting HRD1 may represent a new therapeutic strategy for PTEN
loss hepatocellular carcinoma.
PMID- 29958994
TI - Delay discounting associated with challenges to treatment adherence and glycemic
control in young adults with type 1 diabetes.
AB - INTRODUCTION: Many young adults with type 1 diabetes (T1D) face challenges in
adherence to self-management practices and have above-target HbA1c. Poorer
decision-making skills, indicated by greater delay discounting, may be linked to
these factors. METHODS: An online survey using social media ads targeted young
adults aged 18-26 with T1D. Participants completed the Self-Care Inventory and
the 5-trial delay discounting task and self-reported their last HbA1c value.
RESULTS: Discounting was significantly associated with treatment adherence (r =
.14, p < .05) and HbA1c (r = .18, p < .01). Adherence was also associated with
HbA1c (r = -.26, p < .01). In a hierarchical regression, adding discounting
explained significant additional variance in HbA1c after controlling demographics
(F(1, 257) = 3.99, p < .05); adding adherence next explained significant
additional variance in HbA1c (F(1, 256) = 12.96, p < .01). In the final model,
adherence significantly explained HbA1c variance (beta = -.21, p < .01).
DISCUSSION: These results expand the literature on cognitive factors and glycemic
control among patients with T1D. Factors like delay discounting represent
potentially modifiable risk factors targetable through interventions.
PMID- 29958995
TI - The effects of wet cupping therapy on the blood levels of some heavy metals: a
pilot study.
AB - BACKGROUND AND AIM: Heavy metals have been recognized as toxins for centuries.
Cupping therapy has been shown to aid the excretion of accumulated fluids and
toxins from interstitial fluid. The aim of this study was to investigate the
effects of wet cupping therapy on blood levels of heavy metals. METHODS: Thirteen
healthy male subjects (mean age +/- SD, 28.47 +/- 6.18) participated in this
study. Venous blood samples were collected 5 min before and 30 days after wet
cupping therapy. Five points of the posterior neck and bilateral perispinal areas
of the neck and thoracic spine were selected for cupping therapy. The levels of
aluminium (Al), zinc (Zn), and cadmium (Cd) were measured by Atomic Absorption
Spectrophotometer. RESULTS: The levels of heavy metals (Al, Zn and Cd) after
cupping therapy were significantly lower, compared to the levels before therapy.
CONCLUSIONS: These results suggest that wet cupping therapy has excretory effect
on the kidney. Wet cupping therapy may clear blood from excess heavy metals.
PMID- 29958996
TI - Multiple sub-lethal thresholds for cellular responses to thermal stressors in an
estuarine fish.
AB - Understanding physiological limits and the ability to acclimatize to changing
conditions will determine whether species will be able to cope with further
increases in water temperature. Changes in temperature may be considered to
become stressful for an ectotherm when it results in reduced performance, which
can lead to fitness level consequences. The relative intensity of the stressor as
well as the duration of the exposure to the stressor will determine the response
observed. Transcriptomic responses can potentially indicate thresholds where
physiological performance begins to decline. An understanding of the cellular
shifts throughout the temperature range that an organism experiences in the wild
is often lacking, especially for species of conservation concern such as the
delta smelt (Hypomesus transpacificus). We examined the expression of 15 genes
that represented cellular responses related to stress, growth, cell proliferation
and osmoregulation to show how the response patterns change to acute increases in
temperatures that occur throughout the thermal distribution of the species.
Several genes showed U-shaped or inverted U-shaped response patterns suggesting
the presence of sub-lethal thresholds as temperatures increase. We also highlight
the importance of including a temporal component to exposure studies as several
genes showed a delay in the recovery to control levels at extreme temperatures.
We propose that the non-linear response patterns represent sub-lethal thermal
thresholds that can predict the severity of the response to thermal stressors.
Identifying these sub-lethal thresholds can help differentiate between responses
to routine increases in water temperature and responses that can lead to longer
term fitness impacts.
PMID- 29958997
TI - Hyperglycemia attenuates the association between telomere length and age in
Ukrainian population.
AB - Diabetes-related conditions such as chronic hyperglycemia and related oxidative
stress and inflammation were repeatedly associated with accelerated telomere
shortening in epidemiological studies, although some findings are inconsistent.
In present study, we aimed to assess the impact of disturbances in glucose
metabolism on association between age and leukocyte telomere length (LTL) in the
Ukrainian population. The study was conducted on the 119 adult subjects aged
between 43 and 87 years residing in the Kyiv region, Ukraine. LTL was determined
by a quantitative PCR-based method. LTL was negatively correlated with the
measure of abdominal obesity such as waist-hip ratio, as well as with both
fasting plasma glucose (FPG) and two-hour post-load glucose (2hPG) levels.
Consistently with previous studies, a significant negative association between
LTL and age was observed in individuals with normal (<5.6 mmol/L) FPG levels.
Unexpectedly, however, no association was found in subjects with impaired glucose
metabolism assessed by abnormal FPG or/and 2hPG levels. No association between
LTL and age was observed in a logistic regression model; the association between
LTL and age became significant after adjusting for FPG level. In the FPG-adjusted
model, 1.6-time lower odds to have long telomere length were indicated for each
10 years increase in age. We hypothesize that the attenuation of association
between LTL and age in hyperglycemic persons can likely be attributed to the
interaction of multidirectional processes determining this relationship.
PMID- 29958998
TI - Cortical and hippocampal expression of inflammatory and intracellular signaling
proteins in aged rats submitted to aerobic and resistance physical training.
AB - Aging is often accompanied by an increase in pro-inflammatory markers. This
inflammatory process is directly related to cellular dysfunctions that induce
events such as the exacerbated activation of cell death signaling pathways. In
the aged brain, dysregulation of the normal activities of neuronal cells
compromises brain functions, thereby favoring the onset of neurodegenerative
diseases and cognitive deficits. Interactions between various stimuli, such as
stress, are responsible for the modulation of cellular processes and activities.
Physical exercise is a controllable model of stress, largely used as a strategy
for studying the physiological mechanisms of inflammatory responses and their
consequences. However, different types of physical exercise promote different
responses in the organism. The present study was designed to investigate the
expression of inflammatory cytokines and chemokines, and expression and
activation of intracellular signaling proteins (CREB, ERK, Akt, p70S6k, STAT5,
JNK, NFkB e p38) in the cerebral cortex and hippocampal formation of aged rats
submitted to aerobic and resistance exercise. Inflammatory analysis showed that
aged rats that underwent resistance training had decreased cortical levels of
RANTES and a reduction in the hippocampal levels of MIP-2 when compared with
control animals (sedentary). No significant difference was detected in the
cortical and hippocampal inflammatory response between aerobic and sedentary
groups. However, when comparing the two training models (aerobic vs resistance),
it was observed that aerobic training increased the cortical levels of IL-13, IL
6, IL-17alpha compared with resistance training. Regarding the signaling
proteins, a significant increase in cortical expression of the proteins JNK, ERK
and p70S6k was found in the aerobic group in relation to the sedentary group. No
significant change in the cortical and hippocampal expression of signaling
proteins was detected between resistance training and sedentary groups.
Nevertheless, when training models were compared, it was observed that aerobic
training increased cortical expression of the total proteins p38, ERK, Akt and
p70S6k in relation to resistance training. Taken together, these results show
that changes in the brain expression of inflammatory and cell survival proteins
in aged rats depend on the type of physical training.
PMID- 29958999
TI - Cardiac hypertrophy in sarcopenic obese C57BL/6J mice is independent of Akt/mTOR
cellular signaling.
AB - : Sarcopenic obesity (SO) is the comorbidity of age-related muscle wasting and
obesity. SO increases the risk of heart disease, but little is known about the
cellular signaling in cardiac muscle of SO individuals. AIM: The purpose of this
study was to identify key cellular signaling alterations in cardiac muscle of
sarcopenic obese mice. METHODS: Thirty-two, male C57BL/6J mice were randomly
divided into lean and high-fat fed groups and raised to 3-4 months (young) or 20
22 months (aged) of age. Hearts were extracted and processed for Western blot and
qRT-PCR analyses. RESULTS: Hearts of SO mice were 36-55% heavier than the young,
obese or aged, lean groups. Markers downstream of Akt were not elevated in the SO
group. p-p38:p38 MAPK was higher with age, and a 2-fold increase was observed in
the obese vs. lean aged groups. pERK1/2:ERK1/2 MAPK was ~50-70% lower in the SO
cardiac muscle compared to the young, obese group. pAMPK:AMPK was 50%-66% lower
in the SO cardiac muscle compared to the obese and lean, aged groups. mRNA
abundance of TNFalpha was ~2.5-fold higher in the SO group. CONCLUSION: Cardiac
hypertrophy in SO is likely pathogenic as evidenced by the alterations in MAPK
and AMPK protein content and lack of activation in the Akt/mTOR pathway.
PMID- 29959000
TI - Improving network inference: The impact of false positive and false negative
conclusions about the presence or absence of links.
AB - BACKGROUND: A reliable inference of networks from data is of key interest in the
Neurosciences. Several methods have been suggested in the literature to reliably
determine links in a network. To decide about the presence of links, these
techniques rely on statistical inference, typically controlling the number of
false positives, paying little attention to false negatives. NEW METHOD: In this
paper, by means of a comprehensive simulation study, we analyse the influence of
false positive and false negative conclusions about the presence or absence of
links in a network on the network topology. We show that different values to
balance false positive and false negative conclusions about links should be used
in order to reliably estimate network characteristics. We propose to run careful
simulation studies prior to making potentially erroneous conclusion about the
network topology. RESULTS: Our analysis shows that optimal values to balance
false positive and false negative conclusions about links depend on the network
topology and characteristic of interest. COMPARISON WITH EXISTING METHODS:
Existing methods rely on a choice of the rate for false positive conclusions.
They aim to be sure about individual links rather than the entire network. The
rate of false negative conclusions is typically not investigated. CONCLUSIONS:
Our investigation shows that the balance of false positive and false negative
conclusions about links in a network has to be tuned for any network topology
that is to be estimated. Moreover, within the same network topology, the results
are qualitatively the same for each network characteristic, but the actual values
leading to reliable estimates of the characteristics are different.
PMID- 29959001
TI - Sensory and motivational modulation of immediate and delayed defensive responses
under dynamic threat.
AB - BACKGROUND: Despite the wide variations in defensive behaviors displayed by rats
during predator encounters, most laboratory studies have focused on a limited
number of behaviors, such as immobility in a small enclosure. Other defensive
behaviors such as withdrawal and avoidance have been less investigated. NEW
METHOD: Rats repeatedly encountered a fast threatening motion (snapping claws) of
a robot predator. The robot was equipped with infrared sensors (millisecond
resolution) to detect head entry. A camera placed above arena tracked the body
position (sub-second resolution). Sensory and motivational components regulating
rats' behaviors were investigated. RESULTS: The rats exhibited head-withdrawal
reflex (HWR). The mean HWR speed depended on both the visual and vibrissal
inputs. However, successful escape depended on the vibrissal input. Auditory
information later induced conditioned HWR. Slower defensive behaviors such as the
stretched posture and freezing were modulated by repeated exposure and motivation
level. Introducing a food pellet induced higher rates of approach and elongated
posture while reducing time spent hiding and freezing. COMPARISON WITH EXISTING
METHOD(S): An encounter with a fast-striking claw, while foraging for food is
more ethologically relevant than dermal shocks, which have been widely used for
studying defensive behaviors among rats. More diverse behavioral patterns were
observed. CONCLUSION: A combination of fast and slow defensive behaviors was
exhibited in rats when they were exposed to a dynamic threat. Thus, the use of
the new dynamic threat model will allow for a more accurate investigation of the
various aspects of defensive behavior and emotional regulation in animals.
PMID- 29959002
TI - Rat 50-kHz ultrasonic vocalizations as a tool in studying neurochemical
mechanisms that regulate positive emotional states.
AB - BACKGROUND: Adolescent and adult rats emit 50-kHz ultrasonic vocalizations (USVs)
to communicate the appetitive arousal and the presence of positive emotional
states to conspecifics. NEW METHOD: Based on its communicative function, emission
of 50-kHz USVs is increasingly being evaluated in preclinical studies of
affective behavior, motivation and social behavior. RESULTS: Emission of 50-kHz
USVs is initiated by the activation of dopamine receptors in the shell subregion
of the nucleus accumbens. However, several lines of evidence show that non
dopaminergic receptors may influence the numbers of 50-kHz USVs that are emitted,
as well as the acoustic parameters of calls. COMPARISON WITH EXISTING METHODS:
Emission of 50-kHz USVs is a non-invasive method that may be used to study reward
and motivation without the need for extensive training and complex animal
manipulations. Moreover, emission of 50-kHz USVs can be used alone or combined
with other well-standardized behavioral paradigms (e.g., conditioned place
preference, self-administration). CONCLUSIONS: This review summarizes the current
evidence concerning molecular mechanisms that regulate the emission of 50-kHz
USVs. Moreover, the review discusses the usefulness of 50-kHz USVs as an
experimental tool to investigate how different neurotransmitter systems regulate
the manifestations of positive emotional states, and also use of this tool in
preclinical modeling of psychiatric diseases.
PMID- 29959003
TI - Binding of methimazole and NADP(H) to human FMO3: In vitro and in silico studies.
AB - Human flavin-containing monooxygenase isoform 3 (hFMO3) is an important hepatic
drug-metabolizing enzyme, catalyzing the monooxygenation of nucleophilic
heteroatom-containing xenobiotics. Based on the structure of bacterial FMO, it is
proposed that a conserved asparagine is involved in both NADP(H) and substrate
binding. In order to explore the role of this amino acid in hFMO3, two mutants
were constructed. In the case of N61Q, increasing the steric hindrance above the
flavin N5-C4a causes poor NADP(H) binding, destabilizing the catalytic FAD
intermediate, whereas the introduction of a negatively charged residue, N61D,
interferes mainly with catalytic intermediate formation and its stability. To
better understand the substrate-enzyme interaction, in vitro as well as in silico
experiments were carried out with methimazole as substrate. Methimazole is a high
affinity substrate of hFMO3 and can competitively suppress the metabolism of
other compounds. Our results demonstrate that methimazole Pi-stacks above the
isoalloxazine ring of FAD in hFMO3, in a similar way to indole binding to the
bacterial FMO. However, for hFMO3 indole is found to act as a non-substrate
competitive inhibitor. Finally, understanding the binding mode of methimazole and
indole could be advantageous for development of hFMO3 inhibitors, currently
investigated as a possible treatment strategy for atherosclerosis.
PMID- 29959004
TI - Purification, characterization, molecular modeling and docking study of fish
waste protease.
AB - In the present study, the alkaline protease has been extracted from the fish
processing waste using ammonium sulphate fractionation followed by ion-exchange
chromatography on sephadex G-25 and on DEAE column with a 4.0 fold increase in
purification of yield 7.7%. The molecular weight of the purified protease was
found to be 33 kDa as determined by SDS-PAGE. The optimum temperature was found
to be 30 degrees C at pH 8. The activation energy (Ea) for casein hydrolysis and
temperature quotient (Q10) was found to be 38.25 kJ/mol and 1.65, respectively.
The kinetic constants km, Vmax, kcat, and kcat/km and thermodynamic parameters
DeltaH*, DeltaS*, DeltaG*, DeltaG*E-S, and DeltaG*E-T revealed high affinity of
the fish protease for casein. Using CD spectroscopy it was found that the fish
protease has 32.7% alpha-helical, 32.8% beta-turn and 34.5% random coil. 3D
structure of target protein was predicted by homology modeling. Ramachandran plot
revealed that the total residues in favored, allowed and outlier regions are
96.6%, 2.3%, and 1.1% residues. The biological function of the modeled fish
protease was predicted by COACH based on the I-TASSER model, suggests that the
fish protease may be exploited as biocatalyst in various industrial applications
and processes. AutoDock 4.2.6. was used to study the protein-ligand interactions,
which may lead to the discovery of novel semisynthetic enzymes from renewable
biowaste.
PMID- 29959005
TI - Optical and mechanical properties of pullulan films studied by uniaxial
stretching.
AB - Optical properties of pullulan films were examined before and after uniaxial
stretching to obtain the specific molecular characteristics of pullulan. It was
shown that the specific optical rotation for pullulan film was not affected by
uniaxial stretching, being the same as that for pullulan in aqueous solution.
Combined with the mechanical measurement, the stress-optical coefficient for
pullulan was estimated as a material constant on the basis of the modified stress
optical rule. The birefringence was positive and increased with time during the
stress relaxation of uniaxially-stretched pullulan film. A set of the stress
optical coefficients CR=1.9*10-9Pa-1 and CG=-4.6*10-12Pa-1 were obtained, where
the subscripts R and G stand for the rubber and the glass components
respectively.
PMID- 29959006
TI - Genetic polymorphisms of human transcription factor-7 like 2 (TCF7L2), beta
defensin (DEFB1) and CD14 genes in nephrolithiasis patients.
AB - BACKGROUND: It is assumed that genetic factors play crucial role in
nephrolithiasis. The present study was conducted to explore the role of Human
Transcription Factor-7 like-2 (TCF7L2) beta-defensin (DEFB1) and CD14 gene
polymorphism in development and progression of nephrolithiasis. METHODS: The
genotypes of TCF7L2, DEFB1 and CD14 polymorphism were determined in 240
nephrolithiasis patients and 240 healthy controls by restriction digestion method
of PCR. The levels of serum TCF7L2, DEFB1, CD14, uric acid and other biochemical
parameters were measured both in nephrolithiasis patients and healthy control.
RESULTS: The patients and control groups showed 30% and 50% 1654 AA DEFB1
genotype respectively. The Allele frequency in case of patient's group was 63.67%
while in control group it was 36.33%. The mean serum DEFB1 levels of the patients
and control groups attained were 115.66 and 239.43 pg/mL respectively. The allele
frequency of TCF7L2 in patients and controls were 44.17% and 70.0% for C-allele,
55.83% and 30.00% for T-allele respectively. The mean of serum TCF7L2 levels were
significantly decreased in patients compared to control group. CONCLUSIONS: The
present findings are first of its class that validates a considerable connection
of DEFB1 and TCF7L2 gene polymorphisms with nephrolithiasis and could probably
act as indicators to estimate the risk associated to nephrolithiasis.
PMID- 29959007
TI - Glycosaminoglycans from grey triggerfish and smooth hound skins: Rheological,
Anti-inflammatory and wound healing properties.
AB - The present study aims to evaluate for the first time the wound healing and in
vivo anti-inflammatory effects of glycosaminoglycans from skins of smooth hound
(SHSG) and grey triggerfish (GTSG). Thermal analysis of GTSG and SHSG was
evaluated using differential scanning calorimetry (DSC). The rheologie properties
and water absorption capacity of two gels prepared from SHSG and GTSG were also
studied. The application of GTSG and SHSG based gels on dermal full-thickness
excision wounds in a mouse model, enhanced significantly wound healing activity
and a total closure was achieved after eleven days of wound induction for SHSG.
Further, histological examination of biopsies showed advanced tissue
regeneration, characterized by the presence of well-organized stratum of both
derma and epidermis. The anti-inflammatory evaluation of GTSG and SHSG in mice
showed a significant inhibition of edema paw, after 5 h of carrageenan injection.
The edema inhibition was 91.6% and 90% for SHSG and GTSG, respectively at the
dose of 50 mg/kg. Furthermore, the histological evaluation and the superoxide
dismutase, catalase and malondialdehyde level in muscle tissue were investigated.
In summary, this work demonstrates that both GTSG and SHSG could be promising
drugs with good wound healing and anti-inflammatory effects in animal model.
PMID- 29959008
TI - Structural and functional studies of the Leishmania braziliensis SGT co-chaperone
indicate that it shares structural features with HIP and can interact with both
Hsp90 and Hsp70 with similar affinities.
AB - Molecular chaperones and co-chaperones play an essential role in the life cycles
of protozoa belonging to the genus Leishmania. The small glutamine-rich TPR
containing protein (SGT) is a co-chaperone that can be divided into three
domains: N-terminal, tetratricopeptide (TPR) and C-terminal. The TPR domain is
responsible for interactions with both Hsp70 and Hsp90; however, the mechanism of
interaction and the functionality of SGT are unclear. In this context, we present
the structural and functional characterization of Leishmania braziliensis SGT
(LbSGT), aiming to elucidate how this co-chaperone interacts with the Hsp90/Hsp70
chaperone machinery. Structurally, the recombinant LbSGT behaves as an alpha
helical, multidomain and elongated dimer in solution. Despite their low amino
acid sequence identity and similarity, LbSGT shares structural properties and
domain organization with the Hsp70-interacting protein (HIP) co-chaperone.
Functionally, LbSGT is a cognate protein in L. braziliensis promastigote cells
and interacts indiscriminately, with similar affinities, with both Hsp90 and
Hsp70 chaperones, capable of working as an adaptor protein. Sequence analysis
indicates that LbSGT interacts via a dicarboxylate clamp, the same mechanism used
by the Hsp90-Hsp70-organizing protein (HOP) co-chaperone. These results suggest
that SGT can develop the same function as HOP but using the HIP structural
scaffold.
PMID- 29959009
TI - Facile preparation of bioactive silk fibroin/hyaluronic acid hydrogels.
AB - Proteins and polysaccharides are primary components in mammal soft tissue. In
this study, we established a rapid hydrogel to imitate the nature extracellular
matrix via silk fibroin (SF) and hyaluronic acid (HA) blend hydrogel. SF/HA
hydrogel was prepared effectively, and its formation time was shorted. With the
increase of HA content, the water absorption, porosity and breaking strengths of
the hydrogel increased, while hydrophilic of the hydrogel was enhanced extremely
determined by contact angle decreasing. Especially, the SF/HA hydrogel with a
ratio of 5:5 presented the highest water absorption and mechanical properties.
The molecule conformation of the composite hydrogel was mainly amorphous
structure and contained the small number of beta-sheets which gradually decreases
with the increase of HA content. In drug release test, accumulative release ratio
of the composite gel was about 80% at day 40. And the mass loss of the hydrogel
reached approximately 78% in vitro degradation. In vivo, the SF/HA hydrogels
presented good histocompatibility and promoted vascular-like tissue regeneration
when were implanted subcutaneously of Sprague Dawley rats. This study provides a
new approach to fabricate silk-based biomaterials for soft tissue regeneration.
PMID- 29959010
TI - Characterization of the mitochondrial genomes of three species in the
ectomycorrhizal genus Cantharellus and phylogeny of Agaricomycetes.
AB - Cantharellus is a large ectomycorrhizal genus. Here, we assembled and annotated
the mitochondrial genomes of C. lutescens, C. appalachiensis, and two specimens
of C. cibarius. We found that all four mitochondrial genomes were circular and
between 56,786 bp and 80,736 bp, long. The length and GC content of the protein
coding genes (PCGs) in the four mitogenomes varied. All tRNAs were folded into
classical cloverleaf secondary structures; 16 of the 26 identified tRNAs
contained variable sites across Cantharellus genus. C. appalachiensis was found
containing the most repeated sequences (11.32% of the mitogenome), along with a
substantial number of gene rearrangements. Comparative analysis of three C.
cibarius specimens indicated that the mitogenomes of specimens from different
regions differed. The Ka/Ks ratios of all 15 PCGs identified across all four
mitogenomes were <1, indicating that these genes have been subject to purifying
selection. Phylogenetic analysis recovered a well-supported tree based on a
combined analysis of the 15 PCGs. In addition, we identified cob, cox1, and rnl
as potential single-gene markers for the analysis of phylogenetic relationships
among Agaricomycetes species. The mitogenomes reported in this study will
facilitate the study of population genetics and evolution in Cantharellus and
other closely related species.
PMID- 29959011
TI - Modification of alginate beads using gelatinized and ungelatinized arrowroot
(Tacca leontopetaloides L. Kuntze) starch for drug delivery.
AB - Arrowroot (Tacca leontopetaloides L. Kuntze) starch in gelatinized and
ungelatinized forms was used to modify the characteristics of calcium alginate
(CA) beads containing diclofenac sodium (DS). Sodium alginate (SA) was able to
molecularly interact with ungelatinized starch (UGS) granules and gelatinized
starch (GS) gel via hydrogen bonding mechanisms in the dispersions, leading to
viscosity synergism before cross-linking. The GS-CA beads provided a
significantly higher DS entrapment efficiency than the UGS-CA beads. The added
UGS retarded the water uptake of the CA beads, resulting in slower DS release
profiles in purified water and a longer lag time of DS release in pH 6.8
phosphate buffer. On the other hand, GS enhanced water uptake and accelerated the
DS release of the beads in both media. Moreover, the 1%GS-CA beads displayed
slower DS release than the CA and 1%UGS-CA beads in pH 6.8 phosphate buffer when
simulated gastro-intestinal (GI) condition was used. This study shows that UGS
and GS obtained from Tacca leontopetaloides L. Kuntze have good potential to
improve drug entrapment efficiency of the CA beads, and the DS-loaded GS-CA beads
can be used as multiunit dosage forms for sustaining drug release in simulated GI
condition.
PMID- 29959012
TI - In vitro efficacy of silk sericin microparticles and platelet lysate for
intervertebral disk regeneration.
AB - Intervertebral disk degeneration is an oxidative and inflammatory pathological
condition that induces viability and functionality reduction of Nucleus Pulposus
cells (NPs). Cellular therapies were previously proposed to repair and substitute
the herniated disk but low proliferative index and pathological conditions of NPs
dramatically reduced the efficacy of this approach. To overcome these problems we
proposed, for the first time, a therapeutic system based on the association of
silk sericin microparticles and platelet-derived products. Silk sericin (SS) is a
bioactive protein with marked antioxidant properties, while platelet lysate (PL)
and platelet poor plasma (PPP) represent a source of growth factors able to
support cell viability and to promote tissue regeneration. We demonstrated that
the mixture PL + PPP promoted NPs proliferation with a significant reduction of
cellular doubling time. SS microparticles, alone or in combination with PPP,
presented the higher ROS-scavenging activity while, SS microparticles and PL
resulted as the best association able to protect NPs against oxidative stress
induce by hydroxide peroxide. Based on these results, the authors are confident
that, with the ever increasing need of efficacious tools for regenerative
medicine purposes, SS microparticles and PL + PPP association could represent an
effective approach for the development of low impact and non-invasive therapies.
PMID- 29959013
TI - Optimization of in vitro refolding conditions of recombinant Lepidium draba
peroxidase using design of experiments.
AB - The main objective of this study was to optimize the in vitro refolding
conditions of the recombinant Lepidium draba peroxidase (LDP). Initially, the
effects of various factors were investigated on LDP refolding yield using one
factor-at-a-time (OFAT) method. Based on the OFAT results, optimum concentrations
for LDP refolding were 2 M urea, 2 mM CaCl2, 0.42 mM l-glutathione oxidized
(GSSG), 0.20 mg/ml protein, and 12 MUM hemin as well as pH 7. Secondly, according
to the OFAT results, design of experiments (DOE) was applied for investigation of
the interactions between factors including protein (P), urea (U), CaCl2 (C), and
GSSG (G). The results showed the possible interaction between PC, PG, PU, and GU.
Lastly, response surface methodology (RSM) was used for final refolding
conditions optimization. The final optimized refolding conditions for LDP were
conducted as 2 M urea, 1 mM CaCl2, 0.70 mM GSSG, 0.07 mM DTT, 0.15 mg/ml protein
which they obtained from RSM results and 12 MUM hemin, and pH 7 according to the
results of OFAT method. Overall, under optimal conditions, 23.4 mg active
refolded LDP per liter of expression medium was obtained. So, the refolding yield
was calculated to be approximately 48%.
PMID- 29959014
TI - Effects of high-pressure homogenization on functional properties and structure of
mussel (Mytilus edulis) myofibrillar proteins.
AB - Mussel myofibrillar proteins (MMP) suspensions (10.6% +/- 0.5%, w/v) were treated
by high-pressure homogenization (HPH) at 0 (control), 20, 40, 60, 80 or 100 MPa
for 3 cycles. Particle size distribution, zeta potential, solubility, water and
oil holding capacity, emulsifying, foaming properties, secondary structure, free
sulfhydryl and surface hydrophobicity of the obtained suspensions were analyzed.
The results showed that functional properties of MMP significantly (P < 0.05)
improved after HPH treatment. Absolute zeta potential, emulsifying activity
index, emulsion stability index, foaming ability and foaming stability increased
by 23.64 mV, 14.99 m2/g, 4.3 min, 17.3% and 29.7% at 80 MPa, protein solubility
and oil holding capacity increased by 7.4% and 1300% at 100 MPa. However, HPH
treatment significantly (P < 0.05) decreased particle size and water holding
capacity. HPH treatment altered secondary structure, tertiary and quaternary
structure. Functionality improvements mainly resulted from changes in structure
and decrease in particle size. The results showed that HPH has potential for
improving functional properties of MMP, thus expand its application in food
industry.
PMID- 29959015
TI - Evolution of circadian genes PER and CRY in subterranean rodents.
AB - There is considerable interest in examining how circadian rhythms function and
evolve in subterranean rodents that spend its entire life in underground,
darkness environments. Here, we investigated the evolution of PER and CRY genes
that are important for mammalian biological clocks in the subterranean rodents.
We performed phylogenetic analyses using newly sequenced PER and CRY from the
subterranean rodent Lasiopodomys mandarinus, the related aboveground rodent
Lasiopodomys brandtii, sequences from other rodents available in public
databases. The constructed phylogenetic tree revealed no convergence among
subterranean rodents. Phylogenetic and selection-pressure analyses revealed the
effect of purifying selection (omega < 1) on PER and CRY in subterranean rodents.
Additionally, evidence of positive selection on the CRY1 and PER3 genes in
several subterranean rodent species suggests adaptations to a dark habitat. Most
of the positively selected sites in CRY1 and PER3 were on the C-terminus. Our
findings suggest that PER and CRY are highly conserved during evolution as
subterranean rodents adapted to the darkness environment, and that the C-terminal
domain of CRY1 and PER3 may be the core regulatory structure of circadian
rhythms. The study advances our understanding of how major circadian genes
evolved in subterranean rodents.
PMID- 29959016
TI - Physical, antibacterial and antioxidant properties of chitosan films containing
hardleaf oatchestnut starch and Litsea cubeba oil.
AB - More and more attention was attached to food safety, it is necessary to endow
food packaging films with good antibacterial and antioxidant properties Edible
films based on chitosan (CH), hardleaf oatchestnut starch (HOS) and Litsea cubeba
oil (LEO) were prepared by solution casting. The properties and structures of the
blend film with different proportion (xCH/yHOS) were evaluated. The CH-HOS films
were firstly prepared by blending CH solution with HOS paste. The tensile
strength (TS) and DPPH radical scavenging ability of CH-HOS films increased from
27.33 MPa to 33.54 MPa and 20.67% to 52.34%, respectively, and water vapor
permeability (WVP) decreased from 1.531 * 10-11 g m-1 pa-1 s-1 to 1.491 * 10-11 g
m-1 pa-1 s-1, with the HOS content increased from the ratio of 1:0 to 1:1. Then,
the LEO was added to 1CH-1HOS films. Tensile strength (TS), water vapor
permeability, moisture absorption and total soluble matter (TSM) of the 1CH-1HOS
film were remarkably decreased with 16%LEO. Meanwhile, the static contact angle
and antimicrobial activity of 1CH-1HOS-16LEO film increased significantly. Hence,
this blend film system has great potential for food packaging in the future.
PMID- 29959017
TI - Biochemical characterization of Caulobacter crescentus xylose dehydrogenase.
AB - d-Xylose sugar is a common component of hemicellulose, the second largest
fraction of biomass. Many groups have developed biological conversions of d
xylose to value-added products by recombinant expression of the xylose
dehydrogenase enzyme from Caulobacter crescentus. This enzyme uses NAD+ as a
cofactor to oxidize d-xylose to d-xylono-1,4-lactone. A detailed understanding of
the mechanism of this enzyme could be useful in engineering more efficient
versions. Therefore, we have conducted kinetic studies including both the forward
and reverse physiological reactions of this enzyme. We demonstrate that the
enzyme's substrate binding mode follows a sequential steady state ordered
mechanism with NAD+ or NADH binding first. Furthermore, the kcat of the reaction
in the direction of NAD+ reduction is 10-fold higher than that of the reverse
reaction. From rapid reaction studies, we demonstrate the binding of NAD+ and
NADH to the free enzyme and that hydride transfer occurs in a fast step followed
by a much slower steady state. We calculate that the dissociations of the sugar
products from the enzyme complexes are the major rate limiting steps in both
directions.
PMID- 29959018
TI - Physical properties and antioxidant activity of gelatin-sodium alginate edible
films with tea polyphenols.
AB - Active edible films were prepared by incorporating tea polyphenols (TP) into
gelatin and sodium alginate. The effects of 0.4%-2.0% TP (w/w, TP/gelatin) on
physical, antioxidant, and morphological properties of gelatin-sodium alginate
films were evaluated. Tensile strength (Ts), contact angle (CA), and cross
linking degree showed an enhanced trend as TP concentration in the film
increased, whereas elongation at break (EAB) and water vapor permeability (WVP)
possessed a decline trend. The light transmittance of the film was decreased by
the incorporation of TP. Antioxidant capacity was improved by increasing TP
content in the films. For DPPH and ABTS radical, the films with 2.0% TP possessed
the highest values of 90.62 +/- 2.48% and 53.36 +/- 1.06 Trolox (mg Trolox
equivalent/g film), respectively. Fourier transform infrared spectroscopy
analyses (FTIR) indicated the interactions existed between gelatin-sodium
alginate and TP. Smooth and continuous surface and dense internal structure of
the films with TP were observed by scanning electron microscopy (SEM). Thus,
incorporating TP into gelatin and sodium alginate film solution was an effective
method in order to improve physical properties and antioxidant activity of the
films. Gelatin-sodium alginate films with TP could be used as an edible film for
food packaging applications.
PMID- 29959019
TI - A two-domain folding intermediate of RuBisCO in complex with the GroEL
chaperonin.
AB - The chaperonins (GroEL and GroES in Escherichia coli) are ubiquitous molecular
chaperones that assist a subset of essential substrate proteins to undergo
productive folding to the native state. Using single particle cryo EM and image
processing we have examined complexes of E. coli GroEL with the stringently GroE
dependent substrate enzyme RuBisCO from Rhodospirillum rubrum. Here we present
snapshots of non-native RuBisCO - GroEL complexes. We observe two distinct
substrate densities in the binary complex reminiscent of the two-domain structure
of the RuBisCO subunit, so that this may represent a captured form of an early
folding intermediate. The occupancy of the complex is consistent with the
negative cooperativity of GroEL with respect to substrate binding, in accordance
with earlier mass spectroscopy studies.
PMID- 29959020
TI - Heme degradation and iron release of hemoglobin and oxidative stress of
lymphocyte cells in the presence of silica nanoparticles.
AB - Silica nanoparticles (SiO2 NPs) have been widely used in the medical and food
sciences. However, their toxic effects against bio-macromolecules and cells are
not well understood. The present study was aimed to investigate the adverse
effects of fabricated SiO2 NPs on the human hemoglobin (Hb) by FTIR, CD,
fluorescence, and UV-vis spectroscopic techniques. Moreover, the toxic effects of
SiO2 NPs on the human lymphocyte cell was assessed by trypan blue, reactivate
oxygen species (ROS), and apoptosis assays. It was shown that synthesized SiO2
NPs have an amorphous structure with dominant size of around 20-30 nm. FTIR
results showed that SiO2 NPs bind to Hb and induce significant structural changes
on the native structure of Hb. Near CD spectroscopy depicted that SiO2 NPs
induced tertiary structural changes and heme displacement. Fluorescence
spectroscopy demonstrated the production of heme degradation species in the Hb
solution after interaction with SiO2 NPs. UV-vis spectroscopy experiment
indicated the release of iron form Hb after interaction with SiO2 NPs in a
concentration dependent manner. Live-dead staining, ROS detection and flow
cytometry analysis revealed that human lymphocyte was sensitive towards the
toxicity of SiO2 NPs in a ROS-mediated apoptosis mechanism. In conclusion, SiO2
NPs exhibited concentration-dependent toxicity.
PMID- 29959021
TI - Mapping the B cell epitopes within the major capsid protein L1 of human
papillomavirus type 16.
AB - Persistent infection with human papillomavirus type16 (HPV16) has much
association with the development of cervical cancer. L1 is the major capsid
protein of HPV, it has been well investigated as a potential vaccine candidate.
However, B cell epitopes present on L1 have not been well characterized. To
identify the potential B-cell antigenic epitopes within HPV16 L1 protein, sixteen
serial overlapping truncations (H1-H16) covering the whole region were expressed
in E. coli and used in mice immunization. The mice antisera were tested in ELISA
binding, IFA and HI assays. Finally, four fragments (H2, H4, H11, H12) were found
to contain B cell epitopes of HPV16 L1 protein in ELISA and IFA assays, three
fragments (H2, H3, H9) might contain neutralizing epitopes of HPV16 L1 protein in
HI assay. Among them, H11 and H12 fragments contain B cell epitopes have never
been reported before, and H3 was found as hemagglutination inhibition epitope for
the first time. This work provides new insights to B cell epitopes on HPV16 L1
protein. Several new epitopes were identified and may provide some guidance for
HPV16 subunit vaccine design. The results of this study might open new
perspectives on the antibody-antigen reaction and have important implications for
the development of epitopes-based protective HPV16 vaccines.
PMID- 29959022
TI - Multicenter Evaluation of the Idylla NRAS-BRAF Mutation Test in Metastatic
Colorectal Cancer.
AB - Treatment of colorectal cancer (CRC) with monoclonal antibodies against epidermal
growth factor receptor requires the assessment of the mutational status of exons
2, 3, and 4 of the NRAS and KRAS oncogenes. Moreover, the mutational status of
exon 15 of the BRAF oncogene is a marker of poor prognosis in CRC. The Idylla
NRAS-BRAF Mutation Test is a reliable, simple (<2 minutes hands-on time), and
quick (<2 hours turnaround time) sample-to-result solution, enabling the
detection of clinically relevant mutations in NRAS (18 mutations) and BRAF (5
mutations). A multicenter study was conducted in 14 centers using the Idylla NRAS
BRAF Mutation Test to assess the NRAS and BRAF mutational status of 418 formalin
fixed, paraffin-embedded tissue samples from CRC patients. Results were compared
with those obtained earlier by routine reference methods, including next
generation sequencing, pyrosequencing, mass spectrometry-based assays, PCR-based
assays, and Sanger sequencing. In case of discordance, additional tests were
performed by digital droplet PCR. Overall, after testing confirmation and
excluding invalids/errors by design, concordances between the Idylla NRAS-BRAF
Mutation Test and the reference test results were found in almost perfect
agreement. In conclusion, the Idylla NRAS-BRAF Mutation Test enables the routine
detection of all NRAS and BRAF mutations deemed clinically relevant according to
the latest clinical guidelines, without necessitating molecular expertise or
infrastructure.
PMID- 29959023
TI - Evaluation of a Hepatitis C Virus Core Antigen Assay in Plasma and Dried Blood
Spot Samples.
AB - Simplified, affordable tools to diagnose active hepatitis C virus (HCV) infection
are needed to scale up treatment. This study evaluated the analytical performance
of HCV core antigen (HCVcAg) detection in samples of plasma and dried venous
blood spots (DBSs). Paired plasma and DBS samples were prepared from remnant
diagnostic samples, and plasma HCV RNA and HCVcAg were quantified. Sensitivity
and specificity for HCVcAg (>3 fmol/L) at two HCV RNA thresholds (>=15 and >=3000
IU/mL) were calculated. Of 120 paired samples tested, 25 had nonquantifiable HCV
RNA and 95 had quantifiable HCV RNA. The median HCV RNA level in plasma was 5.6
log10 IU/mL (interquartile range: 5.2 to 6.2). The median HCVcAg levels in plasma
and DBS samples were 2.3 log10 fmol/L (interquartile range: 0.1 to 3.1) and 1.1
log10 fmol/L (interquartile range: 0.0 to 1.9), respectively. For diagnosing HCV
RNA >=3000 IU/mL, the sensitivity and specificity of HCVcAg in plasma were 97.7%
(95% CI, 91%-100%) and 100% (95% CI, 87%-100%), respectively. The sensitivity and
specificity of HCVcAg in DBS were 88.6% (95% CI, 80%-94%) and 97% (95% CI, 82%
100%), respectively. The data from this study demonstrate good sensitivity and
specificity of HCVcAg in plasma at an HCV RNA threshold of >=3000 IU/mL. The
level of HCVcAg quantified in plasma was higher than that in DBS.
PMID- 29959024
TI - Determining Performance Metrics for Targeted Next-Generation Sequencing Panels
Using Reference Materials.
AB - The National Institute of Standards and Technology has developed reference
materials for five human genomes. DNA aliquots are available for purchase, and
the data, analyses, and high-confidence small variant and homozygous reference
calls are freely available on the web. These reference materials are useful for
evaluating whole-genome sequencing methods and also can be used to benchmark
targeted sequencing panels, which are used commonly in clinical settings. This
article describes how to use the Genome in a Bottle samples to obtain performance
metrics on any germline-targeted sequencing panel of interest, as well as the
limitations of the reference materials. These materials are useful for
understanding the limitations of, and optimizing, targeted sequencing panels and
associated bioinformatics pipelines. Example figures are presented to illustrate
ways to access the performance metrics of targeted sequencing panels, and a table
of best practices is included.
PMID- 29959025
TI - Characterization of 108 Genomic DNA Reference Materials for 11 Human Leukocyte
Antigen Loci: A GeT-RM Collaborative Project.
AB - The highly polymorphic human leukocyte antigen (HLA) genes, located in the human
major histocompatibility complex, encode the class I and II antigen-presenting
molecules, which are centrally involved in the immune response. HLA typing is
used for several clinical applications, such as transplantation,
pharmacogenetics, and diagnosis of autoimmune disease. HLA typing is highly
complex because of the homology of HLA genes and pseudogenes and the extensive
polymorphism in the population. The Centers for Disease Control and Prevention
established the Genetic Testing Reference Materials Coordination Program (GeT-RM)
in partnership with the genetics community to improve the availability of genomic
DNA reference materials necessary for quality assurance of genetic laboratory
testing. The GeT-RM together with three clinical laboratories and the Coriell
Cell Repositories have characterized genomic DNA obtained from a panel of 108
cell lines for all HLA classic polymorphic loci: HLA-A, B, C, DRB1, DRB3, DRB4,
DRB5, DQA1, DQB1, DPA1, and DPB1. The goal was to develop a publicly available
and renewable source of well-characterized genomic DNA reference materials to
support molecular HLA typing assay development, validation, and verification,
quality control, and proficiency testing. These genomic DNA samples are publicly
available from the National Institutes of General Medical Science Repository at
the Coriell Cell Repositories.
PMID- 29959026
TI - Toxicokinetics and tolerance of a high energy material 3,4,5-trinitropyrazole
(TNP) in mice.
AB - The high-energy compound 3,4,5-trinitropyrazole (TNP) was developed as an
alternative to other less energetic and more sensitive explosive materials, in
particular 1-methyl-2,4,6-trinitrobenzene (TNT). However, the level of toxicity
of TNP remains understudied. Here using an in vivo CD1 mouse model, we mimicked
an acute exposure (24 h) to TNP, given either orally or intravenously, and
determined the maximum administrable doses (190 mg/kg and 11 mg/kg,
respectively), as well as the lethal dose for 50% (LD50) of female or male mice
(390 mg/kg for both) treated intravenously with TNP alone. Several metabolites
including nitroso-dinitro-pyrazole, hydroxylamino-dinitro-pyrazole, hydroxyl
dinitro-pyrazole and amino-dinitro-pyrazole were identified in urine. TNP is
quickly metabolized and eliminated via urine as two main amino-dinitro-pyrazole
metabolites. A comparison of the transcriptomic effects of TNP and TNT after 10
days exposure enabled us to demonstrate no major induction of transcripts
involved both in cell death mechanisms (apoptosis, necrosis, autophagy) and
physiological pathways (glycolysis, ATP production). Finally, subchronic exposure
to TNP was replicated in female mice, fed 16.8-52.8 mg/kg/day of TNP for one
month, to study the impact on cellular functions. Although blood TNP levels
remained high, a lower rate of TNP accumulation in the liver and lungs were
observed than during an acute exposure. Conversely, cellular stress functions
explored using the RT2 ProfilerTM PCR Array Mouse Molecular Toxicology
PathwayFinder remained unaltered after this chronic exposure. These findings
demonstrate that TNP can be rapidly eliminated in vivo without accumulating in
vital organs.
PMID- 29959027
TI - Nanomaterial exposure and sterile inflammatory reactions.
AB - "Sterile inflammation" is a type of pathogen-free inflammation which may be
induced by various physical, chemical, or metabolic insults, including
environmental particles e.g. silica dioxide crystals and asbestos. The possible
role of nanomaterials as danger signals able to trigger sterile inflammatory
responses is not yet fully understood. Therefore, the aim of this review was to
investigate conditions of sterile inflammation induced by nanomaterial exposure
with a specific focus on possible modes of action. Metal-, metal-oxide- and
carbon-based nanomaterials may trigger a sterile inflammatory cascade by means of
different damage-associated molecular patterns, including chromatin associated
protein high-mobility group box-1 secretion, ATP, ADP and adenosine purinergic
signaling, interleukin-1alpha alarmin, and NLPR-3 inflammasome activation.
However, such preliminary results do not enable us to draw definite conclusions
regarding the sterile inflammatory potential of nanomaterials and possible
underlying molecular mechanisms. Therefore, further research is required to
understand the complex "interplay" between the multitude of nanomaterial
intrinsic or acquired physico-chemical properties and the extremely changeable
immunological competence of organisms. The identification of possible
nanomaterial modes of action in sterile inflammation could provide early
indicators of the biological reactivity of nano-sized chemicals and could direct
"safe by design" efforts for improving occupational safety and that of the
general population. Moreover, the possible pathological consequences of
nanomaterial-induced sterile inflammatory reactions need to be clarified in order
to define suitable preventive measures to protect the health of chronically
exposed subjects.
PMID- 29959028
TI - Resveratrol: An overview of its anti-cancer mechanisms.
AB - Cancer is one of the leading causes of death worldwide. Chemotherapy and
radiotherapy are the conventional primary treatments for cancer patients.
However, most of cancer cells develop resistance to both chemotherapy and
radiotherapy after a period of treatment, besides their lethal side-effects. This
motivated investigators to seek more effective alternatives with fewer side
effects. In the last few years, resveratrol, a natural polyphenolic phytoalexin,
has attracted much attention due to its wide biological effects. In this concise
review, we highlight the role of resveratrol in the prevention and therapy of
cancer with particular focus on colorectal and skin cancer. Also, we discuss the
molecular mechanisms underlying its chemopreventive and therapeutic activity.
Finally, we highlight the problems associated with the clinical application of
resveratrol and how attempts have been made to overcome these drawbacks.
PMID- 29959029
TI - CRIP1 promotes cell migration, invasion and epithelial-mesenchymal transition of
cervical cancer by activating the Wnt/beta-catenin signaling pathway.
AB - Cervical cancer (CC) is the third most common cancer and the fourth leading cause
of malignancy-related mortality in women worldwide. In addition, epithelial
mesenchymal transition (EMT) has been generally studied in tumor metastasis
researches in recent years. Cysteine-rich intestinal protein 1 (CRIP1) is
differently expressed in human cancer cells. However, the role it plays in CC has
not been revealed at present. Preliminary experiments have shown that CRIP1 had a
higher expression in CC tissues, compared with adjacent noncancerous tissues.
Real-time PCR and western blot were performed to analyze CRIP1 expression in CC
cell lines. CRIP1 transient transfection vector and siRNA were constructed.
Further analysis revealed the promotion effects of CRIP1 on the cell migration
and invasion of CC in vitro (P < 0.01). In addition, western blot was performed
to show that CRIP1 mediates EMT by means of EMT marker detection. The expression
of CRIP1 and beta-catenin in CC tissues was analyzed by immunohistochemistry
(IHC). Interestingly, CRIP1 and beta-catenin were both highly expressed in CC
tissues (P < 0.01). Furthermore, CRIP1 increased the protein expression level of
c-myc, cyclinD-1 and cytoplasmic beta-catenin, which are indicators for
activating the Wnt/beta-catenin signaling pathway. In conclusion, CRIP1 promotes
cell migration and invasion, mediates EMT and activates the Wnt/beta-catenin
signaling pathway in CC.
PMID- 29959030
TI - Human melanoma-derived ectosomes are enriched with specific glycan epitopes.
AB - AIMS: Numerous studies confirmed the involvement of extracellular vesicles in
cancer development and progression. The present study was designed to investigate
the glycan composition of ectosomes derived by human cutaneous melanoma (CM) cell
lines with the use of lectins. MAIN METHODS: Ectosomes released by primary
(WM115, WM793) and metastatic (WM266-4, WM1205Lu) CM cells were isolated from
conditioned media by sequential centrifugation. Proteins from ectosomes, the
whole cell extracts and membrane fractions were probed with a panel of lectins
using Western Blot and flow cytometry and compared in terms of disease stage and
glycosignature. KEY FINDINGS: Ectosomal proteins revealed enrichment (mainly with
fucose and complex type N-glycans with bisecting GlcNAc) or depletion of specific
glycoepitopes in comparison to the parental cell membranes. Moreover, similar
lectin binding patterns were observed between related cell lines. It is the first
study to characterize the glycosylation of ectosome proteins released by CM
cells. SIGNIFICANCE: Our data indirectly supports the findings that ectosomes
derive from particular regions of the cell membrane contain a unique glycan
composition, which could serve as a specific sorting signal. If proven correct,
the hypothesis that glycan-based protein sorting is a major mechanism for protein
incorporation into ectosomes may provide new means to control vesicular content
and have possible clinical implications.
PMID- 29959032
TI - Which is the best combination of TACE and Sorafenib for advanced hepatocellular
carcinoma treatment? A systematic review and network meta-analysis.
AB - The aim of this study was to assess the comparative efficacy and safety of
combination therapy with transarterial chemoembolization (TACE) and Sorafenib for
patients with advanced hepatocellular carcinoma (HCC) through a systematic review
and network meta-analysis and identify the best combination of TACE and
Sorafenib. We searched databases for publications prior to May 2018. The
prespecified efficacy outcomes were the objective response rate, overall survival
rate, and time to progression. adverse effects included dermatologic,
gastrointestinal, and general disorders. Subgroup analyses, meta-regression, and
a network meta-analysis regarding two types of outcomes by different chemotherapy
agents in TACE (5-fluorouracil, Adriamycin, Platinum, mitomycin C,
hydroxycamptothecin) were included. The study is registered with PROSPERO
(CRD42018098541). For efficacy outcomes, subgroups which included 5-fluorouracil
and hydroxycamptothecin ranked higher than other chemotherapy agents, while
mitomycin C ranked the lowest. For advanced effects, the use of mitomycin C or 5
fluorouracil as the chemotherapy agent ranked higher, while hydroxycamptothecin
ranked the lowest. Therefore, we excluded 5-Fu and Mitomycin C in subsequent
studies. Additionally, in the evaluation of primary adverse effects by the
network meta-analysis, Platinum ranked the highest while hydroxycamptothecin
ranked the lowest. Therefore, we excluded Platinum this time. Furthermore, all
types of Adriamycin are not same, and some studies included two types of
Adriamycin. The network meta-analysis results showed that the TACE
(hydroxycamptothecin + pirarubicin) +Sorafenib arm and TACE (hydroxycamptothecin
+ epirubicin) +Sorafenib arm had significant efficacy differences. In conclusion,
for patients with advanced HCC, combination therapy with HCPT plus THP/EPI in
TACE and Sorfenib may be used as a first-line treatment.
PMID- 29959031
TI - Changes in left ventricular geometry during antihypertensive treatment.
AB - : The reduction of echocardiographic left ventricular (LV) mass and the change
toward a less concentric geometry during antihypertensive treatment are
independently associated with a better prognosis. Blood pressure-lowering
treatment may reduce cardiac hypertrophy, although different effect on changes of
LV mass have been reported among antihypertensive drug classes, while changes in
echocardiographic evaluated LV geometry have not been systemically evaluated. It
is not yet clear whether antihypertensive drugs may influence LV geometry. Our
aim was to compare the effects of diuretics (D), beta-blockers (BB), calcium
channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACE-I), and
angiotensin receptor blockers (ARBS) on relative wall thickness (RWT) in patients
with hypertension on the basis of prospective, randomized comparative studies.
METHODS: MEDLINE, and the ISI Web of Sciences were searched for randomized
clinical trials evaluating LV mass and geometry at baseline and end follow-up. We
have performed a pooled pairwise comparisons of the effect of the 5 major drug
classes on relative wall thickness changes, and of each drug class versus other
classes statistically combined. RESULTS: We selected 53 publications involving
7684 patients. A significant correlation was observed between percent changes
from baseline to end of treatment in LV mass and those in systolic BP (r = 0.44,
p < 0.001). Reduction of LV mass was significantly greater with CCB than with BB
(P < 0.02) without other significant differences between drug classes. Percent
changes in RWT were related to percent changes in LV mass/LVmass index (r = 0.68,
p = 0.016) and of SBP (r = 0.64 p < 0.033). RWT decreased during treatment with
all classes of drugs, except the combination of BB and D; the decrease of RWT was
less with diuretics and sympatholytic drugs. CONCLUSIONS: In studies evaluating
the effect of different classes of antihypertensive drugs on LV mass, the
reduction of relative wall thickness seems to be less during treatment with
diuretics.
PMID- 29959033
TI - A meta-learning framework using representation learning to predict drug-drug
interaction.
AB - MOTIVATION: Predicting Drug-Drug Interaction (DDI) has become a crucial step in
the drug discovery and development process, owing to the rise in the number of
drugs co-administered with other drugs. Consequently, the usage of computational
methods for DDI prediction can greatly help in reducing the costs of in vitro
experiments done during the drug development process. With lots of emergent data
sources that describe the properties and relationships between drugs and drug
related entities (gene, protein, disease, and side effects), an integrated
approach that uses multiple data sources would be most effective. METHOD: We
propose a semi-supervised learning framework which utilizes representation
learning, positive-unlabeled (PU) learning and meta-learning efficiently to
predict the drug interactions. Information from multiple data sources is used to
create feature networks, which is used to learn the meta-knowledge about the
DDIs. Given that DDIs have only positive labeled data, a PU learning-based
classifier is used to generate meta-knowledge from feature networks. Finally, a
meta-classifier that combines the predicted probability of interaction from the
meta-knowledge learnt is designed. RESULTS: Node2vec, a network representation
learning method and bagging SVM, a PU learning algorithm, are used in this work.
Both representation learning and PU learning algorithms improve the performance
of the system by 22% and 12.7% respectively. The meta-classifier performs better
and predicts more reliable DDIs than the base classifiers.
PMID- 29959034
TI - Linking the concentrations of itraconazole and 2-hydroxypropyl-beta-cyclodextrin
in human intestinal fluids after oral intake of Sporanox(r).
AB - In a previously performed small-scale clinical study, healthy volunteers were
asked to ingest an oral solution of itraconazole (Sporanox(r)) containing 40% 2
hydroxypropyl-beta-cyclodextrin (HP-beta-CD) (i) with or (ii) without a
standardized volume of water (240 mL) after which gastrointestinal and blood
samples were collected. Although omitting water during the administration of
Sporanox(r) resulted in noticeably higher duodenal concentrations of
itraconazole, systemic exposure was almost unaffected. It is assumed that this
discrepancy can be explained by differences in the extent of entrapment of
itraconazole in the duodenum caused by differential complexation depending on the
concentration of cyclodextrins. To further substantiate this hypothesis, the
quantification of HP-beta-CD concentrations in the aspirated intestinal fluids
was performed by LC-MS/MS. When comparing the intestinal concentrations of
itraconazole and HP-beta-CD for one single healthy volunteer (HV02) in both test
conditions, an excellent correlation was observed (Spearman's rank coefficient of
0.96). Moreover, the data suggest that, similar to aqueous buffer media, also in
human intestinal fluids a non-linear relationship exists between itraconazole
solubility and HP-beta-CD concentration (Ap-type profile; Spearman's rank
coefficient of 0.78), indicating that higher order complexes are formed at higher
concentrations of HP-beta-CD. This difference in extent of entrapment in the
inclusion complexes helps to understand the observed impact of water intake on
precipitation and permeation behavior of itraconazole in man. Without water
intake, higher HP-beta-CD concentrations resulted in less precipitation and
increased duodenal concentrations of itraconazole. On the other hand, the
stronger interaction at higher HP-beta-CD concentrations reduced the free
fraction of the drug explaining that increased intraluminal concentrations of
itraconazole were not translated into an enhanced uptake. In conclusion,
quantifying the concentrations of the solubilizing agent HP-beta-CD in human
intestinal fluids appeared to be of crucial importance to interpret the
intraluminal behavior of an orally administered cyclodextrin-based solution.
PMID- 29959036
TI - Development of vaccine for Clostridium difficile infection using membrane
fraction of nontoxigenic Clostridium difficile.
AB - Although standard antibiotic therapy is performed for diarrhea and
pseudomembranous colitis caused by Clostridium difficile, a high recurrence rate
of C. difficile infection (CDI) remains a major problem. We previously showed
that a membrane fraction of nontoxigenic C. difficile (ntCDMF) was effective as a
vaccine antigen by in vitro experiments. In this study, we examined whether
ntCDMF had an in vivo effect in animal challenge experiments. By intrarectal
immunization with ntCDMF, the number of C. difficile cells in feces of mice was
decreased approximately 99% compared to the control mice. In addition, survival
rate of C. difficile-challenged hamsters was increased almost 30% by immunization
with ntCDMF. These results showed that ntCDMF could be a practical vaccine
candidate.
PMID- 29959035
TI - Selective staining and eradication of cancer cells by protein-carrying DARPin
functionalized liposomes.
AB - Since their discovery, liposomes have been widely employed in biomedical
research. These nano-size spherical vesicles consisting one or few phospholipid
bilayers surrounding an aqueous core are capable of carrying a wide variety of
bioactive compounds, including drugs, peptides, nucleic acids, proteins and
others. Despite considerable success achieved in synthesis of liposome constructs
containing bioactive compounds, preparation of ligand-targeted liposomes
comprising large quantities of encapsulated proteins that are capable of
affecting pathological cells still remains a big challenge. Here we described a
novel method for preparation of small (80-90 nm in diameter) unilamellar
liposomes containing very large quantities (thousands of protein molecules per
liposome) of heme-containing cytochrome c, highly fluorescent mCherry and highly
toxic PE40 (Pseudomonas aeruginosa Exotoxin A domain). Efficient encapsulation of
the proteins was achieved through electrostatic interaction between positively
charged proteins (at pH lower than pI) and negatively charged liposome membrane.
The proteoliposomes containing large quantities of mCherry or PE40 and
functionalized with designed ankyrin repeat protein (DARPin)_9-29, which targets
human epidermal growth factor receptor 2 (HER2) were shown to specifically stain
and kill in sub-nanomolar concentrations HER2-positive cells, overexpressing
HER2, respectively. Specific staining and eradication of the receptor-positive
cells demonstrated here makes the DARPin-functionalized liposomes carrying large
quantities of fluorescent and/or toxic proteins a promising candidate for tumor
detection and therapy.
PMID- 29959037
TI - Melaleuca alternifolia essential oil prevents bioenergetics dysfunction in spleen
of silver catfish naturally infected with Ichthyophthirius multifiliis.
AB - Some evidence has demonstrated that Ichthyophthirius multifiliis, etiologic agent
of "white spot disease", causes severe bioenergetics dysfunction in the spleen of
naturally infected silver catfish (Rhamdia quelen), which contributes directly to
disease pathogenesis. Recently, several studies have demonstrated the efficacy of
Melaleuca alternifolia essential oil, popularly known as tea tree oil (TTO), in
the treatment of freshwater fish naturally or experimentally infected with I.
multifiliis. In this sense, the aim of this study was to evaluate whether TTO is
capable of preventing or reducing splenic bioenergetics dysfunction in silver
catfish naturally infected with I. multifiliis. Splenic cytosolic and
mitochondrial creatine kinase (CK) and pyruvate kinase (PK) activities decreased
in infected animals compared to uninfected animals, while adenylate kinase (AK)
activity increased. Treatment with TTO was able to prevent the inhibition on
splenic CK and PK activities but was not able to prevent the stimulation of AK
activity. Based on this evidence, treatment with TTO prevents the impairment on
energetic metabolism via improvement of enzymes belonging to the phosphotransfer
network, such as CK and PK. In summary, this treatment can be considered an
interesting approach to prevent the bioenergetics imbalance in spleen of silver
catfish naturally infected with I. multifiliis.
PMID- 29959038
TI - Isolation and characterization of Metarhizium anisopliae TK29 and its
mycoinsecticide effects against subterranean termite Coptotermes formosanus.
AB - The entomopathogenic fungus Metarhizium anisopliae is widely used as biocontrol
agent against many insect pests. In the present study, the potential isolate of
M. anisopliae TK29 was isolated from the agricultural soils in Thekkady, India.
The taxonomic identity of the isolate was confirmed based on its morphology and
18S rDNA gene sequence homology. Phylogenetic analysis confirmed that the
isolated strains were related to the same species. A potential isolate (TK29) was
optimized for mass cultivation and conidial spore production was enhanced using
three different raw substrates (Rice, Maize, black gram) by solid-state
fermentation. The results showed higher conidial spore yield from rice (2.6 +/-
0.32%) compared to black gram (2.1 +/- 0.28%) and maize (1.9 +/- 0.23%)
substrates. Dry green conidia were applied against Formosan subterranean termite,
Coptotermes formosanus at three different concentrations (1 * 106, 1 * 107, and 1
* 108 conidia/ml-1). The highest mortality rate was obtained from 1 * 108
conidia/ml-1 at 120 h post-treatment. Our study indicated that M. anisopliae TK29
had desirable attributes for the development of a mycoinsecticide against C.
formosanus.
PMID- 29959039
TI - Characterization of inter-Sertoli cell tight and gap junctions in the testis of
turtle: Protect the developing germ cells from an immune response.
AB - It is conceivable that early developing germ cells must across the basal to the
luminal region of seminiferous tubules (STs) during spermatogenesis is associated
with extensive restructuring of junctional complex. However, very limited
information is documented about these junctional complexes in reptiles. In the
present study we have determined the localization of inter-Sertoli cell tight
junctions (TJ's), protein CLDN11 and gap junction protein Cx43 during
spermatogenesis in the testis. In early spermatogenesis, weak immunoreactivity of
CLDN11and focal localization of Cx43 was observed around the Sertoli cell in the
luminal region, but completely delaminated from the basal compartment of STs. In
late spermatogenesis, strong focal to linear localization of CLDN11and Cx43 was
detected at the points of contact between two Sertoli cells and around the early
stages of primary spermatocytes in the basal compartment of STs. In late
spermatogenesis, localization of CLDN11and Cx43 was drastically reduced and seen
only around Sertoli cells and spermatogonia near the basal lamina. However,
transmission electron microscopy revealed that inter-Sertoli cell tight junctions
were present within the basal compartment of STs, leaving the spermatogonia and
early primary spermatocytes in the basal region during mid spermatogenesis. Gap
junctions were observed between Sertoli cells, and Sertoli cells with
spermatogonia and primary spermatocytes throughout spermatogenesis. Moreover,
adherens and hemidesmosomes junctions were observed during spermatogenesis. The
above findings collectively suggest that the intensity and localization of TJ's
and gap junctions vary according to the spermatogenetic stages that might be
protected the developing germ cells from own immune response.
PMID- 29959040
TI - In-silico designing, chemical synthesis, characterization and in-vitro assessment
of antibacterial properties of some analogues of curcumin.
AB - In the present work two key regulator proteins, monomeric MipZ of Caulobacter
vibrioides (similar to Pseudomonas aeruginosa) and Pyruvate kinase of
Staphylococcus aureus were docked with curcumin, the wonder molecule from the
spice turmeric and structures of its twelve analogues were designed, synthesized
and tested in-vitro for antibacterial activity. Based on the test results a
comparative account of the probable mechanism has been given Two major
alternative targets are possible for antibacterial activity of drug molecules.
These may be bacterial cell wall lipids or the proteins responsible for smooth
functioning of bacterial cells. In the former case, due to significant difference
in the structural components of the cell walls of Gram positive and Gram negative
bacteria, it is improbable that same ligand will affect both equally. Majority of
commercial drugs are anti-Gram negative bacteria while in the present work we
have found most effective drugs against Gram positive bacteria. Based on the test
results a comparative account of the probable mechanism has been given. Evidently
along with the cell wall damaging mechanism other parallel mechanisms are also
operative.
PMID- 29959041
TI - Coupling xylitol with remineralizing agents improves tooth protection against
demineralization but reduces antibiofilm effect.
AB - To explore the efficiency of xylitol chewing gum enriched or not with
remineralizing agents to protect tooth against cariogenic biofilm formation and
demineralization. Six groups of chewing gums were prepared; Group 1: isomalt
(1.8%), Group 2: casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) (3%)
+ isomalt (1.8%), Group 3: hydroxyapatite (HAP) (2.5%) + isomalt (1.8%), Group 4:
xylitol (1.8%), Group 5: CPP-ACP (3%) + xylitol (1.8%) and Group 6: HAP (2.5%) +
xylitol (1.8%). The antibiofilm properties of different chewing gum extracts
using seven oral bacterial species including Streptococcus mutans, Streptococcus
constellatus, Streptococcus Salivarius and Streptococcus oralis were explored via
the crystal violet staining assay. The remineralizing effects of those products
were assessed on thirty human permanent teeth, half-protected with varnish before
chemical erosion and thermocycling process with chewing gum. Remineralization was
evaluated using scanning electron microscopy and microscopic measurements on
polarized light microscopy. The ratio R comparing the thickness between
unvarnished and varnished sides was evaluated. While the minimum biofilm
inhibitory concentration (MBIC50) was low for xylitol alone compared to isomalt,
it was inconsistent when enriched with remineralizing agents. The minimum biofilm
eradication concentration (MBEC50) was low for xylitol groups compared to
isomalt, for all the studied strains. R was significantly lower in Group 1 and
Group 2, while Group 6 showed the highest ratio. Xylitol chewing gums confirmed
good antibiofilm properties and showed remineralized potential on eroded teeth.
When xylitol is associated to CPP-ACP or HAP, antibiofilm activity decreased
while remineralization of eroded teeth increased.
PMID- 29959042
TI - Application of high-resolution melting-curve analysis on pvpA gene for detection
and classification of Mycoplasma gallisepticum strains.
AB - Mycoplasma gallisepticum (MG) is an avian species pathogen which causes heavy
economic losses in the poultry industry. The purpose of this study was to
determine genomic diversity of 14 MG field strains from chicken, Chuker partridge
and peacock collected during 2009-2012 in Iran by polymerase chain reaction and
partial sequencing of the pvpA gene. A High-Resolution Melting (HRM) technique
was also developed and applied to differentiate between field and vaccine
strains. Sequencing of the pvpA gene revealed a 51 nucleotide deletion, within DR
1 and DR-2, among MG strains from chicken and partridge whilst 63 nucleotides
were deleted in MG strain from peacock. One nucleotide substitution was also
observed among chicken MG strains. Phylogenetic analysis of the sequences
clustered all of the Iranian MG strains into two clades or phylogeny groups; the
strains from chicken and partridge in one group (group 1) and the strain from
peacock into another group (group 4). HRM analysis has also produced comparable
outcome to those of sequencing; four distinct melting curves which correspond to
the three MG strains from chicken, Chukar partridge and peacock and ts-11 vaccine
strain. Overall, findings of this study point towards a single source of
infection for the chicken and partridge MG strains and likelihood of the strains
being native and endemic in Iran. Peacock considered as an exotic species in
Iran, hence the genetic distance for the pvpA gene. MG can be transmitted easily
among different avian species and this distinct peacock strain may pose a threat
to poultry industry. Our findings also show that molecular variation among pvpA
gene of MG strains could be revealed using the relatively rapid and affordable
HRM technique.
PMID- 29959043
TI - Protection elicited by nasal immunization with pneumococcal surface protein A
(PspA) adjuvanted with bacterium-like particles against Streptococcus pneumoniae
infection in mice.
AB - Streptococcus pneumoniae is a major respiratory tract pathogen causing high
levels of mortality and morbidity in infants and the elderly. In spite of the
multitude of capsular polysaccharide vaccines used to guard against pneumococcal
disease, fatal pneumococcal disease remains epidemic. Immunization with
pneumococcal surface protein A (PspA), a highly immunogenic surface protein
present in all strains of S. pneumoniae, can elicit protection against deadly
pneumococcal infection. We have previously evaluated PspA in systemic
vaccination. However, the mucosal immune system, as a first line of defense
against respiratory infection, plays the most important role against the invasion
of S. pneumoniae. In this study, we employed bacterium-like particles (BLPs) as
an adjuvant for a PspA mucosal vaccine. The BLPs served as a carrier for PspA
proteins bound to their surface. Mice were immunized intranasally with the PspA
BLP pneumococcal vaccine consisting of PspA3 from pneumococcal family 2. Not only
did the immunized mice show a high level of serum IgG antibodies but also a high
level of SIgA antibodies in the respiratory tract. After immunization with the
PspA3-BLP vaccine, the mice were broadly protected against fatal intranasal
challenge with homologous and heterogenous pneumococcal strains of different PspA
families regardless of serotype, and the colony count was notably decreased in
the lungs. Therefore, the PspA3-BLP pneumococcal vaccine has the potential to
serve as a novel mucosal vaccine to enhance both systemic and mucosal immune
responses to this disease.
PMID- 29959044
TI - Transcription factor VmSeb1 is required for the growth, development, and
virulence in Valsa mali.
AB - Transcription factor Seb1 contains two C2H2 zinc finger motifs which are similar
to the Msn2/4 of Saccharomyces cerevisiae. The homologous proteins of Seb1
function to regulate the response to various stresses or decomposing and
utilizing pectin in some fungi. In this study, we characterized a homologue of
Seb1 gene, VmSeb1, in Valsa mali, which causes a highly destructive bark disease
on apple. VmSeb1 deletion mutant showed a drastic reduction in growth rate in
vitro. It is also important for conidiation because VmSeb1 deletion mutant formed
more pycnidia on PDA medium. Deletion mutant of VmSeb1 increased melanin genes
expression. In addition, the sensitivity to oxidative stress increased and cell
wall inhibitor in VmSeb1 deletion mutant, as its growth was more severely
inhibited by H2O2 and Congo red than that in the wild-type. The virulence assay
showed that the lesion length caused by the VmSeb1 deletion mutant was smaller
compared to wild-type on detached apple twigs. However, expression of pectinase
genes and pectinase activity in deletion mutant were the same as those of the
wild-type during infection. These results indicate that VmSeb1 plays important
roles in growth, asexual development, response to oxidative stress, maintenance
of cell wall integrity, and virulence. However, VmSeb1 is not involved in the
regulation of pectinase genes expression in V. mali.
PMID- 29959045
TI - Is MED13L-related intellectual disability a recognizable syndrome?
AB - INTRODUCTION: MED13L-related intellectual disability is characterized by moderate
intellectual disability (ID), speech impairment, and dysmorphic facial features.
We present 8 patients with MED13L-related intellectual disability and review the
literature for phenotypical and genetic aspects of previously described patients.
MATERIALS AND METHODS: In the search for genetic aberrations in individuals with
ID, two of the patients were identified by chromosomal microarray analysis, and
five by exome sequencing. One of the individuals, suspected of MED13L-related
intellectual disability, based on clinical features, was identified by Sanger
sequencing. RESULTS: All 8 individuals had de novo MED13L aberrations, including
two intragenic microdeletions, two frameshift, three nonsense variants, and one
missense variant. Phenotypically, they all had intellectual disability, speech
and motor delay, and features of the mouth (open mouth appearance, macroglossia,
and/or macrostomia). Two individuals were diagnosed with autism, and one had
autistic features. One had complex congenital heart defect, and one had
persistent foramen ovale. The literature was reviewed with respect to clinical
and dysmorphic features, and genetic aberrations. CONCLUSIONS: Even if most
clinical features of MED13L-related intellectual disability are rather non
specific, the syndrome may be suspected in some individuals based on the
association of developmental delay, speech impairment, bulbous nasal tip, and
macroglossia, macrostomia, or open mouth appearance.
PMID- 29959046
TI - Age-specific gray and white matter DTI atlas for human brain at 33, 36 and 39
postmenstrual weeks.
AB - During the 3rd trimester, dramatic structural changes take place in the human
brain, underlying the neural circuit formation. The survival rate of premature
infants has increased significantly in recent years. The large morphological
differences of the preterm brain at 33 or 36 postmenstrual weeks (PMW) from the
brain at 40PMW (full term) make it necessary to establish age-specific atlases
for preterm brains. In this study, with high quality (1.5 * 1.5 * 1.6 mm3 imaging
resolution) diffusion tensor imaging (DTI) data obtained from 84 healthy preterm
and term-born neonates, we established age-specific preterm and term-born brain
templates and atlases at 33, 36 and 39PMW. Age-specific DTI templates include a
single-subject template, a population-averaged template with linear
transformation and a population-averaged template with nonlinear transformation.
Each of the age-specific DTI atlases includes comprehensive labeling of 126 major
gray matter (GM) and white matter (WM) structures, specifically 52 cerebral
cortical structures, 40 cerebral WM structures, 22 brainstem and cerebellar
structures and 12 subcortical GM structures. From 33 to 39 PMW, dramatic
morphological changes of delineated individual neural structures such as
ganglionic eminence and uncinate fasciculus were revealed. The evaluation based
on measurements of Dice ratio and L1 error suggested reliable and reproducible
automated labels from the age-matched atlases compared to labels from manual
delineation. Applying these atlases to automatically and effectively delineate
microstructural changes of major WM tracts during the 3rd trimester was
demonstrated. The established age-specific DTI templates and atlases of 33, 36
and 39 PMW brains may be used for not only understanding normal functional and
structural maturational processes but also detecting biomarkers of neural
disorders in the preterm brains.
PMID- 29959047
TI - 1/f electrophysiological spectra in resting and drug-induced states can be
explained by the dynamics of multiple oscillatory relaxation processes.
AB - Neurophysiological recordings are dominated by arhythmical activity whose spectra
can be characterised by power-law functions, and on this basis are often referred
to as reflecting scale-free brain dynamics (1/fbeta). Relatively little is known
regarding the neural generators and temporal dynamics of this arhythmical
behaviour compared to rhythmical behaviour. Here we used Irregularly Resampled
AutoSpectral Analysis (IRASA) to quantify beta, in both the high (5-100 Hz,
betahf) and low frequency bands (0.1-2.5 Hz, betalf) in MEG/EEG/ECoG recordings
and to separate arhythmical from rhythmical modes of activity, such as, alpha
rhythms. In MEG/EEG/ECoG data, we demonstrate that oscillatory alpha power
dynamically correlates over time with betahf and similarly, participants with
higher rhythmical alpha power have higher betahf. In a series of pharmaco-MEG
investigations using the GABA reuptake inhibitor tiagabine, the glutamatergic
AMPA receptor antagonist perampanel, the NMDA receptor antagonist ketamine and
the mixed partial serotonergic agonist LSD, a variety of effects on both betahf
and betalf were observed. Additionally, strong modulations of betahf were seen in
monkey ECoG data during general anaesthesia using propofol and ketamine. We
develop and test a unifying model which can explain, the 1/f nature of
electrophysiological spectra, their dynamic interaction with oscillatory rhythms
as well as the sensitivity of 1/f activity to drug interventions by considering
electrophysiological spectra as being generated by a collection of stochastically
perturbed damped oscillators having a distribution of relaxation rates.
PMID- 29959048
TI - Exercise-induced neuroplasticity: Balance training increases cortical thickness
in visual and vestibular cortical regions.
AB - Physical exercise has been shown to induce structural plasticity in the human
brain and to enhance cognitive functions. While previous studies focused on
aerobic exercise, suggesting a link between increased cardiorespiratory fitness
and exercise-induced neuroplasticity, recent findings have suggested that whole
body exercise with minor metabolic demands elicits beneficial effects on brain
structure as well. In the present study, we tested if balance training,
challenging the sensory-motor system and vestibular self-motion perception,
induces structural plasticity. Thirty-seven healthy adults aged 19-65 years were
randomly assigned to either a balance training or a relaxation training group.
All participants exercised twice a week for 12 weeks. Assessments before and
after the training included a balance test and the acquisition of high-resolution
T1-weighted images to analyze morphological brain changes. Only the balance group
significantly improved balance performance after training. Cortical thickness was
increased in the superior temporal cortex, in visual association cortices, in the
posterior cingulate cortex, in the superior frontal sulcus, and in the precentral
gyri in the balance group, compared to the relaxation group. Moreover, there was
evidence that the balance training resulted in decreased putamen volume. Improved
balance performance correlated with the increase of precentral cortical thickness
and the decrease in putamen volume. The results suggest that balance training
elicits neuroplasticity in brain regions associated with visual and vestibular
self-motion perception. As these regions are known for their role in spatial
orienting and memory, stimulating visual-vestibular pathways during self-motion
might mediate beneficial effects of physical exercise on cognition.
PMID- 29959049
TI - Sounds enhance visual completion processes.
AB - Everyday vision includes the detection of stimuli, figure-ground segregation, as
well as object localization and recognition. Such processes must often surmount
impoverished or noisy conditions; borders are perceived despite occlusion or
absent contrast gradients. These illusory contours (ICs) are an example of so
called mid-level vision, with an event-related potential (ERP) correlate at ~100
150 ms post-stimulus onset and originating within lateral-occipital cortices (the
ICeffect). Presently, visual completion processes supporting IC perception are
considered exclusively visual; any influence from other sensory modalities is
currently unknown. It is now well-established that multisensory processes can
influence both low-level vision (e.g. detection) as well as higher-level object
recognition. By contrast, it is unknown if mid-level vision exhibits multisensory
benefits and, if so, through what mechanisms. We hypothesized that sounds would
impact the ICeffect. We recorded 128-channel ERPs from 17 healthy, sighted
participants who viewed ICs or no-contour (NC) counterparts either in the
presence or absence of task-irrelevant sounds. The ICeffect was enhanced by
sounds and resulted in the recruitment of a distinct configuration of active
brain areas over the 70-170 ms post-stimulus period. IC-related source-level
activity within the lateral occipital cortex (LOC), inferior parietal lobe (IPL),
as well as primary visual cortex (V1) were enhanced by sounds. Moreover, the
activity in these regions was correlated when sounds were present, but not when
absent. Results from a control experiment, which employed amodal variants of the
stimuli, suggested that sounds impact the perceived brightness of the IC rather
than shape formation per se. We provide the first demonstration that multisensory
processes augment mid-level vision and everyday visual completion processes, and
that one of the mechanisms is brightness enhancement. These results have
important implications for the design of treatments and/or visual aids for low
vision patients.
PMID- 29959050
TI - Interleukin 15 blockade protects the brain from cerebral ischemia-reperfusion
injury.
AB - Acute ischemic stroke is followed by a complex interplay between the brain and
the immune system in which ischemia-reperfusion leads to a detrimental
inflammatory response that causes brain injury. In the brain, IL-15 is expressed
by astrocytes, neurons and microglia. Previous study showed that ischemia
reperfusion induces expression of IL-15 by astrocytes. Transgenic over-expression
of IL-15 in astrocytes aggravates ischemia-reperfusion brain damage by increasing
the levels and promoting the effector functions of CD8+ T and NK cells. Treatment
of neonatal rats with IL-15 neutralizing antibody before hypoxia-ischemia
induction reduces the infarct volume. However, as stroke-induced inflammatory
responses differ between neonate and adult brain, the effects of IL-15 blockade
on the injury and immune response arising from stroke in adult animals has
remained unclear. In this study, we examined the effect of post
ischemia/reperfusion IL-15 blockade on the pathophysiology of cerebral ischemia
reperfusion in adult mice. Using a cerebral ischemia-reperfusion model, we
compared infarct size and the infiltrating immune cells in the brain of wild type
(WT) mice and Il15-/- mice lacking NK and memory CD8+ T cells. We also evaluated
the effects of IL-15 neutralizing antibody treatment on brain infarct volume,
motor function, and the status of brain-infiltrating immune cells in WT mice.
Il15-/- mice show a smaller infarct volume and lower numbers of activated brain
infiltrating NK, CD8+ T, and CD4+ T cells compared to WT mice after cerebral
ischemia-reperfusion. Post-ischemia/reperfusion IL-15 blockade reduces infarct
size and improves motor and locomotor activity. Furthermore, IL-15 blockade
reduces the effector function of NK, CD8+ T, and CD4+ T cells in the ischemia
reperfusion brain of WT mice. Ablation of IL-15 responses after cerebral ischemia
reperfusion ameliorates brain injury in adult mice. Therefore, targeting IL-15 is
a potential effective therapy for ischemic stroke.
PMID- 29959051
TI - Three bisabolane-type sesquiterpenes from edible mushroom Pleurotus eryngii.
AB - Three bisabolane-type sesquiterpenes (1-3) were isolated from the fruiting bodies
of king trumpet mushrooms (Pleurotus eryngii), together with a known compound
(4). All isolated compounds were evaluated for their inhibitory effects on nitric
oxide (NO) production. Among these, 2 exhibited a moderate inhibitory effect on
NO production with an IC50 of 90.9 MUM.
PMID- 29959052
TI - Triterpene saponins with neuroprotective effects from the leaves of Diospyros
kaki Thunb.
AB - Seven undescribed triterpene saponins, named kakisaponin I-VII (1-7), together
with nine known ones (8-16) were isolated from the leaves of Diospyros kaki
Thunb. by various chromatographic methods. Compounds 1-5 were novel 18, 19
secoursane triterpenoids, which were an uncommon type of triterpenoids. Their
structures were elucidated by different spectroscopic methods, combining HRESIMS,
1D and 2D NMR. All isolated compounds were evaluated for their protective effects
on H2O2-induced damage in human dopaminergic neuroblastoma cells (SH-SY5Y).
Compound 2 showed significant neuroprotective effect at a certain concentration,
and compounds 3 and 12 exhibited moderate bioactivities. Current study suggests
that triterpene saponins in Diospyros kaki may play an important role in the
neuroprotective properties.
PMID- 29959053
TI - Supplementation with resveratrol as Polygonum cuspidatum Sieb. et Zucc. extract
induces changes in the excretion of urinary markers associated to aging in rats.
AB - An UPLC-HR-MS metabolomics approach was used to study the effects of a 49-days
oral supplementation with Polygonum cuspidatum extract in healthy rats.
Multivariate analysis allowed to observe significant differences in the excretion
of several markers between treated animals and control group. Among the others,
the amounts of N-methyl-2-pyridone-5-carboxamide (2PY) and phenylacetylglycine
(PAG) were reduced in the treated group compared to control. These compounds have
been previously considered as markers of aging. Furthermore, the excretion of 3
hydroxysebacic acid and 4,6-dihydroxyquinoline was also changed following
supplementation, although not significantly. Despite the relatively short time of
treatment (7 weeks), the significant changes in the urinary levels of aging
markers observed at day 49 suggests a potential role of this type of studies as a
new approach in the evaluation of the anti-aging effects of plant extracts.
PMID- 29959054
TI - Pimpinelol, a novel atypical Sesquiterpene lactone from Pimpinella haussknechtii
fruits with evaluation of endoplasmic reticulum stress in breast cancer cells.
AB - Pimpinella haussknechtii is an annual native plant grows in west of Iran.
Phytochemical study of the fruits of P. haussknechtii led to the isolation of a
novel irregular sesquiterpene lactone with a new skeletone and oxidation pattern
named: pimpinelol. The structure of the isolated compound was elucidated by
extensive spectroscopic methods. Cytotoxic activity of Pimpinelol was evaluated
using standard MTT assay against breast cancer cells. Induced endoplasmic
reticulum stress and related gene expressions were evaluated with fluorescence
microscopy analysis and real time PCR, respectively. These findings confirmed
that Pimpinelol concentrations dependently increased protein aggregation and the
mRNA expression of ATF-4, CHOP, GADD34 and TRIB3 in MCF-7 breast cancer cell
line. According to the obtain results, we demonstrated for the first time that
Pimpinelol decreased breast cancer cell viability by inducing ER stress.
PMID- 29959055
TI - The multifaceted role of glutathione S-transferases in cancer.
AB - Glutathione S-transferases (GSTs) are phase II detoxifying enzymes involved in
the maintenance of cell integrity, oxidative stress and protection against DNA
damage by catalyzing the conjugation of glutathione to a wide variety of
electrophilic substrates. Though enzymes of the glutathione synthesis and salvage
pathways have been well characterized in the past, there is still a lack of
comprehensive understanding of their independent and coordinate regulatory
mechanisms in carcinogenesis. The present review discusses implication of GST in
cancer development and progression, gene polymorphism, drug resistance, signaling
and epigenetic regulation involving their role in cancer. It is anticipated that
GST especially the GSTP1 class can be developed as a biomarker either used alone
or in combination with other biomarkers for early cancer detection and/or
diagnosis as well as for future targeted preventive and therapeutic interventions
with dietary agents.
PMID- 29959056
TI - Genetically-engineered Salmonella typhimurium expressing TIMP-2 as a therapeutic
intervention in an orthotopic glioma mouse model.
AB - Glioma is one of the most devastating and refractory cancers. The main factors
underlying therapeutic failure include extremely invasive characteristics and
lack of effective methods for drug delivery. Attenuated Salmonella strains
presented a high concentration of tumor targets in various types of cancer
models, suggesting a role as potential vectors for drug delivery. In this study,
we genetically engineered an attenuated strain of Salmonella as an anti-invasive
vector for the targeted delivery and expression of tissue inhibitor of
metalloproteinases 2 (TIMP-2) in an orthotopic nude mouse model of glioma. The
bioluminescence signals related to tumor size significantly declined in the TIMP
2-expressing Salmonella (SLpTIMP-2)-treated group compared with the control
group. Compared with the control group with a survival rate of an average of 33
days, the SLpTIMP-2 group showed an extended survival rate by nearly 60% and
lasted an average period of 53 days with TIMP-2 induction. These results
indicated the promising therapeutic potential of S. typhimurium for targeted
delivery and secretion of TIMP-2 in glioma.
PMID- 29959057
TI - Glycogen synthase kinase 3 inhibition lowers PD-1 expression, promotes long-term
survival and memory generation in antigen-specific CAR-T cells.
AB - Successful remission in hematological cancers by CAR-T cell immunotherapy has yet
to be replicated in solid tumors like GBM. A significant impediment of CAR-T
immunotherapy in solid tumors is poor exposure of T cells to tumor antigens
resulting in suboptimal CAR-T cell activation, which ultimately fails to induce a
robust anti-tumor immune response. Costimulatory moieties in advanced-generation
CARs, along with additional IL2 therapy has been shown to be insufficient to
overcome this hurdle and have its cytotoxic limitations. GSK3 is constitutively
active in naive T cells and is transiently inactivated during T cell activation
resulting in rapid T cell proliferation. Pharmacologic inhibition of GSK3 in GBM
specific CAR-T cells reduced FasL expression, increased T cell proliferation and
reduced exhaustion by lowering PD-1 levels resulting in the development of CAR-T
effector memory phenotype. Treatment with GSK3-inhibited CAR-T cells resulted in
100% tumor elimination during the tumor-rechallenge experiment in GBM-bearing
animals and increased accumulation of memory CAR-T cells in secondary lymphoid
organs. These adjuvant-like effects of GSK3 inhibition on activated CAR-T cells
may be a valuable adjunct to a successful implementation of CAR-T immunotherapy
against GBM and other solid tumors.
PMID- 29959058
TI - Cleavage of peptidic inhibitors by target protease is caused by peptide
conformational transition.
AB - Some peptide sequences can behave as either substrates or inhibitors of serine
proteases. Working with a cyclic peptidic inhibitor of the serine protease
urokinase-type plasminogen activator (uPA), we have now demonstrated a new
mechanism for an inhibitor-to-substrate switch. The peptide, CSWRGLENHAAC (upain
2), is a competitive inhibitor of human uPA, but is also slowly converted to a
substrate in which the bond between Arg4 and Gly5 (the P1-P1' bond) is cleaved.
Substituting the P2 residue Trp3 to an Ala or substituting the P1 Arg4 residue
with 4-guanidino-phenylalanine strongly increased the substrate cleavage rate. We
studied the structural basis for the inhibitor-to-substrate switch by determining
the crystal structures of the various peptide variants in complex with the
catalytic domain of uPA. While the slowly cleaved peptides bound clearly in
inhibitory mode, with the oxyanion hole blocked by the side chain of the P3'
residue Glu7, peptides behaving essentially as substrates with a much accelerated
rate of cleavage was observed to be bound to the enzyme in substrate mode. Our
analysis reveals that the inhibitor-to-substrate switch was associated with a 7 A
translocation of the P2 residue, and we conclude that the inhibitor-to-substrate
switch of upain-2 is a result of a major conformational change in the enzyme
bound state of the peptide. This conclusion is in contrast to findings with so
called standard mechanism inhibitors in which the inhibitor-to-substrate switch
is linked to minor conformational changes in the backbone of the inhibitory
peptide stretch.
PMID- 29959059
TI - Trophoblast Glycoprotein is Associated With a Favorable Outcome for Mesothelioma
and a Target for Antibody Drug Conjugates.
AB - INTRODUCTION: The prognosis for patients with mesothelioma is poor, which prompts
the need for the development of better treatment options. Antibody drug
conjugates (ADCs) are gaining interest as a therapeutic strategy in mesothelioma.
Trophoblast glycoprotein (5T4) is an oncofetal protein overexpressed in
mesothelioma with low expression in normal tissue and therefore a good candidate
for ADC treatment. Here, we evaluated and manipulated 5T4 as a suitable antigen
for ADC targeted therapy in patients with mesothelioma. METHODS: Expression of
the 5T4 antigen is evaluated in (primary) mesothelioma cell lines and biopsy
specimens, and correlated with clinical outcome. Internalization was assessed in
5T4 expressing cells. The cytotoxicity of three different 5T4-targeting ADCs was
tested on (primary) mesothelioma cells. RESULTS: 5T4 was expressed in 10 of 12
(primary) cell lines. Most biopsy specimens stained positive for the 5T4 antigen,
with marked differences in staining intensity and percentage of positive cells.
High expression correlated with long progression-free survival. Both free
antibody and ADCs targeting 5T4 were internalized and entered lysosomal
compartments. Cytotoxicity experiments showed that cell lines with a high
expression for 5T4 were sensitive to two of three ADCs. Lack of efficacy for the
third ADC could be restored by neutralizing lysosomal compartments with
chloroquine. CONCLUSIONS: The 5T4 antigen is expressed in mesothelioma and 5T4
based ADCs are internalized in lysosomes. Two of three ADCs were capable of
killing the mesothelioma cells; the third ADC required additional lysosomal
neutralization for its effect. 5T4-based ADCs would be a selective strategy for
the treatment of mesothelioma.
PMID- 29959060
TI - Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients
After Stereotactic Ablative Radiotherapy.
AB - INTRODUCTION: It remains unclear if histology should be independently considered
when choosing stereotactic ablative body radiotherapy dose prescriptions for
NSCLC. METHODS: The study population included 508 patients with 561 lesions
between 2000 and 2016, of which 442 patients with 482 lesions had complete
dosimetric information. Eligible patients had histologically or clinically
diagnosed early-stage NSCLC and were treated with 3 to 5 fractions. The primary
endpoint was in-field tumor control censored by either death or progression.
Involved lobe control was also assessed. RESULTS: At 6.7 years median follow-up,
3-year in-field control, involved lobe control, overall survival, and progression
free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross
tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p
= 0.0225) were independently associated with involved lobe failure. GTV (HR =
1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose
with alpha/beta = 10 [BED10], HR = 2.380, p = 0.0084) were independently
associated with in-field failure. For squamous cell carcinomas, lower
prescription doses were associated with worse in-field control (12 Gy * 4 or 10
Gy * 5 versus 18 Gy or 20 Gy * 3: HR = 3.530, p = 0.0447, confirmed by propensity
score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence
interval: 1.005-1.022, p = 0.0012). For adenocarcinomas, there were no
differences in in-field control observed using the above dose groupings (p = 0.12
and p = 0.31, respectively). CONCLUSIONS: In the absence of level I data, GTV and
histology should be considered to personalize radiation dose for stereotactic
ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy * 4
or 10 G * 5) should be avoided for squamous cell carcinomas if normal tissue
tolerances are met.
PMID- 29959061
TI - Prevalence of reported percutaneous injuries on dentists: A meta-analysis.
AB - OBJECTIVES: To answer the focused question, "What are the prevalence of
percutaneous injuries (PIs) on dentists, the location with the highest
prevalence, and the dental instrument most responsible for these injuries?" As
secondary outcomes, the prevalence by geographic location, type of PI, sex
distribution, and dentist's specialty were also considered. ELIGIBILITY CRITERIA:
Observational descriptive studies investigating the prevalence of percutaneous
injuries on dentists were included. SOURCES: Five electronic databases and three
partial grey literature searches were performed. RISK OF BIAS: The MAStARI tool
assessed the potential risk of bias (RoB) among the studies, while the GRADE
approach determined the level of evidence. INCLUDED STUDIES: Among 2284
identified studies, 55 were included. Three studies were classified as low RoB,
17 as moderate RoB, and 35 as high RoB. The sample size ranged from 9 to 4107
dentists. SYNTHESIS OF RESULTS: The PI prevalence in dentists ranged from 7.72%
(95% confidence interval [CI]: 0.93-37.59) to 66.74% (95%CI: 29.83-94.51). North
America was the most affected region, while South America was the least affected.
Differences between sexes were not significant. The dental bur was the most
commonly reported dental instrument causing PIs. LIMITATIONS: Owing to the very
low GRADE level of evidence, caution should be applied when considering these
findings and further research is required. CONCLUSIONS: A high PI prevalence
among dentists was noticed, and most were caused by dental burs. These findings
imply that PIs should be considered by every dentist and proper measures
instituted to reduce their prevalence.
PMID- 29959062
TI - Bone augmentation using autogenous bone versus biomaterial in the posterior
region of atrophic mandibles: A systematic review and meta-analysis.
AB - OBJECTIVES: This systematic review and meta-analysis aimed to answer the PICO
question: "Do patients who have received bone grafts with bone substitute
(biomaterials) present bone gain (before implant installation), complications,
and implant survival rates similar to autogenous grafts when used in the
posterior mandible region?". DATA: This review followed the PRISMA statement and
has been registered at PROSPERO (CRD42016048471). Studies published in English,
randomized controlled and/or prospective clinical trials with at least 10
patients, and studies that compared grafts with bone substitutes to autogenous
bone grafts (split-mouth design) were included. SOURCES: An electronic search and
a manual search were conducted in PubMed/MEDLINE, Scopus, and Cochrane databases
up to April 2018. STUDY SELECTION: Our initial search yielded 640 articles; we
selected four articles that met the inclusion criteria. All selected studies used
a split-mouth design. RESULTS: Our analysis revealed no significant difference
between the biomaterial and autogenous groups in terms of bone gain (P = 0.11;
mean difference [MD]: 0.59; 95% confidence interval [CI]: -0.13-1.31) or
complication rate (P = 0.72; risk ratio [RR]: 1.25; 95% CI: 0.37-4.23). Sixty-six
implants were installed in the biomaterial group and 63 in the autogenous group;
these showed no significant difference in implant survival rate (P = 0.50; RR:
1.57; 95% CI: 0.43-5.81). CONCLUSION: We conclude that biomaterials or autogenous
bone are indicated for the reconstruction of the posterior mandibular atrophic
region, without lowering implant survival.
PMID- 29959063
TI - Apurinic/apyrimidinic endonuclease Apn1 from Saccharomyces cerevisiae is
recruited to the nucleotide incision repair pathway: Kinetic and structural
features.
AB - Apurinic/apyrimidinic endonuclease Apn1 of Saccharomyces cerevisiae is known as a
key player of the base excision DNA repair (BER) pathway in yeast. BER is
initiated by DNA glycosylases, whereas Apn1 can start DNA repair individually in
the nucleotide incision repair (NIR) pathway. The aim of this research was to
elucidate kinetic and structural dynamic aspects of Apn1 involvement in the NIR
process. One of the key characteristics of AP endonuclease's interactions is
known to be divalent metal ions playing a part of a cofactor. Well-studied human
APE1 employs Mg2+ ions, with metal ion concentration's affecting enzymatic
activity exerted by APE1. In our study, we aimed to test the effect of the Mg2+
ion on Apn1's NIR catalysis by examining structural dynamics of DNA during the
interaction in real time using the stopped-flow technique. To test NIR activity
of Apn1, deoxyribooligonucleotide duplexes containing a 5,6-dihydro-2'
deoxyuridine (DHU) residue were employed as substrates. A 2-aminopurine (2-aPu)
residue was a reporter group fluorescence intensity of which was detected during
Apn1-DNA interactions. NIR activity of both WT and H83A Apn1 was found to be
arrested during the interaction with a DNA duplex containing the 2-aPu residue
upstream of DHU. We conducted molecular dynamics simulations to elucidate the
structural features of complexes of the enzyme with DHU-containing DNAs. The NIR
recruiting S. cerevisiae Apn1 proceeds via multistep rearrangements of the
complex of Apn1 with a DHU-containing DNA substrate and results in the incised
product of the reaction. For wild-type Apn1, the catalytic rate constants do not
depend on the Mg2+ concentration, i.e., they are equal in NIR and BER buffers,
with equilibrium association constant Ka being 10-fold higher in NIR buffer. Our
data reveal more delicate regulation of Apn1's NIR activity due to the more
complicated kinetic mechanism, as compared to BER.
PMID- 29959064
TI - Dihydrodipicolinate synthase is absent in fungi.
AB - The class I aldolase dihydrodipicolinate synthase (DHDPS) catalyzes the first
committed step of the diaminopimelate (DAP) lysine biosynthesis pathway in
bacteria, archaea and plants. Despite the existence, in databases, of numerous
fungal sequences annotated as DHDPS, its presence in fungi has been the subject
of contradictory claims. We report the characterization of DHDPS candidates from
fungi. Firstly, the putative DHDPS from Coccidioides immitis (PDB ID: 3QFE) was
shown to have negligible enzyme activity. Sequence analysis of 3QFE showed that
three out of the seven amino acid residues critical for DHDPS activity are
absent; however, exact matches to catalytic residues from two other class I
aldolases, 2-keto-3-deoxygluconate aldolase (KDGA), and 4-hydroxy-2-oxoglutarate
aldolase (HOGA), were identified. The presence of both KDGA and HOGA activity in
3QFE was confirmed in vitro using enzyme assays, the first report of such dual
activity. Subsequent analyses of all publically available fungal sequences
revealed that no entry contains all seven residues important for DHDPS function.
The candidate with the highest number of identities (6 of 7), KIW77228 from
Fonsecaea pedrosoi, was shown to have trace DHDPS activity in vitro, partially
restored by substitution of the seventh critical residue, and to be incapable of
complementing DHDPS-deficient E. coli cells. Combined with the presence of all
seven sequences for the alternative alpha-aminoadipate (AAA) lysine biosynthesis
pathway in C. immitis and F. pedrosoi, we believe that DHDPS and the DAP pathway
are absent in fungi, and further, that robust informed methods for annotating
genes need to be implemented.
PMID- 29959065
TI - LncRNA THOR attenuates cisplatin sensitivity of nasopharyngeal carcinoma cells
via enhancing cells stemness.
AB - The roles and mechanisms of long non-coding RNAs (lncRNA) in nasopharyngeal
carcinoma (NPC) cells stemness and chemotherapeutic sensitivity are unclear.
Here, Quantitative real-time PCR (qRT-PCR) was performed to detect the lncRNA
THOR expression in NPC and normal adjacent tissues, adherent NPC cells and non
adherent NPC spheres, and we found that THOR was significantly increased in NPC
tissues and non-adherent NPC spheres. Further in vitro and in vivo experiments
were carried out and identified that knockdown of THOR attenuated NPC cells
stemness, characterized as the decrease of spheres formation ability, cell
proliferation, migration, invasion, stemness markers expression and tumor
initiation, and enhanced cisplatin sensitivity of NPC cells. Mechanistically, RNA
immunoprecipitation (RIP), immunofluorescence and luciferase reporter analysis
indicated that THOR could enhance YAP transcriptional activity via directly
binding to YAP and suppressing its translocation from nuclear to cytoplasm.
Notably, overexpression of YAP rescued the inhibition of THOR knockdown on NPC
cells and spheres stemness and promotion on cisplatin sensitivity. Thus, our
results demonstrate that lncRNA THOR could attenuate cisplatin sensitivity of NPC
cells by enhancing cells stemness through promoting YAP transcriptional activity.
PMID- 29959066
TI - Low-Dose versus Therapeutic Range Intravenous Unfractionated Heparin Prophylaxis
in the Treatment of Patients with Severe Aneurysmal Subarachnoid Hemorrhage After
Aneurysm Occlusion.
AB - BACKGROUND: While prophylaxis with intravenous unfractionated heparin (UFH) can
effectively prevent venous thromboembolism (VTE) during the neurocritical care of
patients with severe aneurysmal subarachnoid hemorrhage (aSAH), the risk for
intracranial bleeding complications might increase. Owing to this therapeutic
dilemma, the UFH administration regimen in this critical patient population
remains highly controversial. METHODS: We performed a retrospective analysis of
patients with severe aSAH (Fisher grade 3-4) receiving either low-dose (activated
partial thromboplastin time [aPTT] <40 seconds) or therapeutic range (aPTT 50-60
seconds) UFH during intensive care unit (ICU) treatment after complete
surgical/endovascular aneurysm occlusion. The primary outcome was the rate of
bleeding/VTE complications and the investigation of potential risk factors.
RESULTS: This study series comprised 410 patients with aneurysmal SAH (aSAH),
with a mean age of 54.7 +/- 12.6 years, a male:female ratio of 1:2.2, and aSAH
associated intracerebral hemorrhage (ICH) in 33.2%. After complete aneurysm
occlusion, 112 patients (27.3%) received therapeutic dose UFH and 298 patients
(72.7%) received low-dose UFH. VTE events occurred in 5.4% of the low-dose UFH
cohort and in 6.3% of the therapeutic dose UFH cohort, with no significant
differences in the rate and severity of VTE events. However, an increase in
initial SAH-associated ICH was significantly (P = 0.007) more frequent in the
therapeutic dose cohort (18.8% vs. 3.4%). Heparin-induced thrombocytopenia (HIT)
was the sole risk factor for VTE (P < 0.001), and both an aPTT >=50 seconds under
UFH administration (P = 0.007) and the initial presence of SAH-associated ICH (P
= 0.035) were significant risk factors for intracranial bleeding complications.
CONCLUSIONS: Even in high-risk neurocritical patients with severe SAH and
prolonged ICU treatment, low-dose UFH-administration for VTE prophylaxis is
equally effective as therapeutic UFH administration and carries a lower risk of
bleeding complications.
PMID- 29959067
TI - Tailoring Endoscopic Approach to Colloid Cysts of the Third Ventricle: A
Multicenter Experience.
AB - BACKGROUND: Endoscopic removal of third ventricular colloid cysts has grown in
popularity. The biggest issues concern radicality, cure or at least long-term
control of the disease, and endoscopic remnants. Technologic advances in
instrumentation and introduction of novel tools have greatly improved endoscopic
results. Deeper knowledge of surrounding anatomy and awareness that colloid cysts
vary in their position (foraminal or retroforaminal) can further improve with the
selection of a tailored approach for each patient. METHODS: During the last 12
years, 22 colloid cysts were treated endoscopically in our centers. Cysts were
classified into 3 groups: A, foraminal (n = 6); B, foraminal with retroforaminal
extension (n = 10); C, retroforaminal (n = 6). The following entry points and
trajectories were selected: precoronal foraminal (n = 7), precoronal
retroforaminal (n = 4), precoronal combined retroforaminal/foraminal (n = 5),
supraorbital foraminal (n = 6). Navigation guidance was used in 17 cases.
RESULTS: Major complications resulted in permanent deficits in 1 case, and 2
other patients experienced transient memory impairment. Remnants were noted by
surgeon's intraoperative assessment in 6 cases; only 2 remnants were large,
whereas the others were small bits of coagulated cyst stem. In 18 cases, no
remnant was found on postoperative magnetic resonance imaging. CONCLUSIONS: A
traditional precoronal transforaminal approach should be considered only for pure
foraminal cysts (group A), as the retroforaminal component is poorly controlled.
Retroforaminal cysts (groups B and C) should be resected through a retroforaminal
transpellucidum interfornicialis route. A supraorbital transforaminal approach is
a more versatile approach suitable for most cases.
PMID- 29959068
TI - Clinical Outcome of Epidural Hematoma Treated Surgically in the Era of Modern
Resuscitation and Trauma Care.
AB - OBJECTIVE: Patients from contemporary populations with traumatic brain injury
(TBI) resulting from epidural hematoma (EDH) may differ regarding age,
comorbidities, and coagulation status. We therefore analyzed predictors for the
clinical outcome of patients with EDH treated surgically regarding modern
approaches to resuscitation and trauma care. METHODS: A retrospective
observational analysis was carried out. All patients included underwent surgery.
The indication for surgery followed international guidelines. Retrospective data
evaluation considered data reflecting the effectiveness of trauma care, baseline
characteristics, and radiologic findings. In this analysis, we divided patients
into 2 groups (isolated EDH vs. EDH plus other intracranial traumatic injuries).
The neurologic outcome was assessed at discharge using the Glasgow Outcome Scale.
RESULTS: Two hundred and sixty-eight patients with epidural hematoma, of whom 131
underwent surgery, were treated between January 1997 and December 2012 in our
level-1 trauma center. The overall mortality was 6.8% (mortality for patients
with Glasgow Outcome Scale score <9, 15%). As expected, factors with a highly
significant (P < 0.01) impact on outcome were concomitant with other intracranial
injuries, brain midline shift, and higher Injury Severity Score. Alcohol
intoxication was a significant (P < 0.05) predictor of an unfavorable outcome.
Anticoagulants and Glasgow Coma Scale score at admission had no significant
impact on the outcome. CONCLUSIONS: The outcome for EDH is more favorable than
decades ago, most probably reflecting a well-established chain of trauma care.
Therefore, EDH is a treatable disease with a high probability of a favorable
outcome.
PMID- 29959069
TI - Results of Early and Late Surgical Decompression and Stabilization for Acute
Traumatic Cervical Spinal Cord Injury in Patients with Concomitant Chest
Injuries.
AB - BACKGROUND: The benefits of early surgical decompression and stabilisation
(within 24 hours of injury) for patients with acute traumatic spinal cord injury
(SCI) is unclear. The study objective was to investigate the effects of early
(<24 hours of injury) versus late (>24 hours of injury) decompressive and
stabilisation surgery for traumatic cervical SCI in patients with concomitant
chest injuries. METHODS: This was a retrospective study including adults aged 16
years or over with traumatic cervical SCI, Glasgow Coma Scale score >13, and
concomitant chest injuries (e.g. hemopneumothoraces, flail chest and pulmonary
contusions) necessitating intensive care unit (ICU) admission. Forty patients who
met the inclusion criteria and underwent decompressive surgery within 24 hours
were compared with 55 patients who underwent decompressive surgery after 24
hours. Primary outcomes were ordinal change in the ASIA Impairment Scale (AIS) at
6 months and duration of ICU stay. Secondary outcomes included complications
occurring within 30 days. RESULTS: In the early surgery group, 21 patients
(52.5%) showed no improvement in ASIA grade, 13 (32.5%) had a 1-grade
improvement, and 6 (15%) had a 2-grade improvement. The median length of ICU stay
was 14 days (range, 2-68). 42.5% of patients developed a complication and 45%
required a tracheostomy. In the late surgery group, AIS grade improvement was as
follows: 32 (58%) no improvement, 19 (34.5%) had a 1 grade improvement, 3 (5.5%)
had a 2 grade improvement and 1 (2%) had a 3 grade improvement. Mean ICU stay was
23 days (4-68). 53% of patients developed a complication and 55% required a
tracheostomy. There was one mortality in the late surgery group. CONCLUSIONS: For
patients with acute traumatic cervical SCI and concomitant chest trauma, early
surgical decompression and stabilisation was associated with reduced ICU stay and
a lower complication rate. Neurological recovery was more likely in younger
patients and those with an incomplete SCI.
PMID- 29959070
TI - Intraoperative and Postoperative Bleeding in Microvascular Decompression for
Trigeminal Neuralgia.
AB - OBJECTIVE: The surgical approach for the trigeminal nerve involves veins
connected to the superior petrosal and tentorial sinus, and we should pay special
attention to these veins. We investigated intraoperative and postoperative
bleeding using our database. METHODS: A prospectively accumulated database of 247
microvascular decompression surgeries for trigeminal neuralgia over the past 10
years was analyzed. Intraoperative and postoperative bleeding was confirmed with
surgical records, videos, and computed tomography. Of 235 patients, 161 were
female; 85 patients were >70 years old at the time of surgery; 96 surgeries
involved the left side. RESULTS: Intraoperative venous bleeding was encountered
in 29 surgeries (12%): from the superior petrosal vein/sinus in 18 and the
hemispheric bridging vein/tentorial sinus in 11. Massive bleeding occurred from
the superior petrosal sinus owing to tear of the entrance of the superior
petrosal vein in 4 surgeries and from the tentorial sinus in 3; bleeding was
controlled by Surgicel with fibrin glue. Postoperative bleeding occurred in 11
surgeries (4%): intracerebellar hematoma in 2, subarachnoid hemorrhage in 3,
subdural hemorrhage in 3, supratentorial subdural hemorrhage in 2, and
supratentorial epidural hematoma in 1. These lesions were associated with
intraoperative bleeding in 1 case, a trans-horizontal fissure approach in 1 case,
coagulation of the petrosal vein in 2 cases, and unknown reasons in 7 cases. Cure
without medication was achieved in 218 surgeries at an average follow-up of 4.2
years. CONCLUSIONS: Microvascular decompression for trigeminal neuralgia involves
potential risks of intraoperative and postoperative bleeding.
PMID- 29959071
TI - Abdominal Complications of Ventriculoperitoneal Shunt in Pediatric Patients:
Experiences of a Pediatric Surgery Clinic.
AB - OBJECTIVE: To relate the experiences of a pediatric surgery clinic in diagnosis
and treatment of abdominal complications related to ventriculoperitoneal shunts
(VPSs) in pediatric patients who had VPSs implanted to treat hydrocephalus.
METHODS: Patients admitted to the Pediatric Surgery Department of Van Yuzunciyil
University Faculty of Medicine between April 2013 and December 2017 who had VPSs
implanted and subsequently developed abdominal complications were reviewed
retrospectively. Demographic information, surgery dates, time intervals between
surgery and development of abdominal complication, complication types and applied
treatments, and follow-up durations were recorded. RESULTS: There were 16
patients (6 girls, 10 boys) with a mean age of 3 years (range, 1 month to 8
years) reviewed. Complications following VPS implantation included abdominal
pseudocyst, anal protrusion, volvulus, peritonitis, abdominal distention, and
herniation. Complications were treated successfully with contemporary surgical
methods. No issues during long-term postoperative follow-up were identified.
CONCLUSIONS: VPS implantation can result in abdominal complications with a wide
range of clinical presentations. Predicting which abdominal complications might
occur in children with VPSs can be lifesaving with early diagnosis and treatment.
PMID- 29959072
TI - The Clinical Efficacy of Electromagnetic Navigation-Guided Hematoma Puncture
Drainage in Patients with Hypertensive Basal Ganglia Hemorrhage.
AB - OBJECTIVE: To investigate the clinical efficacy of navigation-guided minimally
invasive surgery in patients with hypertensive basal ganglia hemorrhage. METHODS:
A total of 64 patients with hypertensive basal ganglia hemorrhage were enrolled
in this retrospective study. They were divided into a navigation group and a
traditional group based on surgical approaches. The data for the 2 groups of
patients were analyzed with regard for the hematoma clearance rate, duration of
surgery, duration of hospitalization, Glasgow Outcome Scale score at discharge,
Barthel index score at 6 months, and postoperative complication rates for
rebleeding and pneumonia. RESULTS: There were no significant differences in basic
characteristics between the 2 groups (P > 0.05). The hematoma clearance rate was
significantly lower in the navigation group (49.18 +/- 16.76%) than in the
traditional group (84.29 +/- 6.91%, P < 0.01). The duration of surgery and
duration of hospitalization were significantly shorter in the navigation group
(55.00 +/- 11.89 minutes and 24.25 +/- 7.1 days, respectively) than in the
traditional group (156.38 +/- 47.9 minutes and 32.63 +/- 9.8 days, respectively;
both P < 0.01). There were also significant differences between the 2 groups in
Glasgow Outcome Scale scores (P = 0.006). The Barthel index scores were
significantly greater in the navigation group (73.13 +/- 18.76) than in the
traditional group (57.63 +/- 26.63, P < 0.05). There were no significant
differences between the 2 groups in the complication rates (P > 0.05).
CONCLUSIONS: Under certain conditions, compared with standard craniotomy and
hematoma evacuation, navigation-guided hematoma puncture aspiration and catheter
drainage is simple, effective, and safe as a treatment for hypertensive basal
ganglia hemorrhage.
PMID- 29959073
TI - Embolization of Ruptured Distal Lenticulostriate Artery Aneurysms.
AB - OBJECTIVE: To describe the critical role of endovascular treatment and safety for
the patients who presented with intraventricular hemorrhage owing to rupture of
the distal lenticulostriate artery aneurysms. METHODS: Three patients who
underwent endovascular treatment for distal lenticulostriate artery aneurysms
related to intraventricular hemorrhage were selected and retrospectively
reviewed. RESULTS: Patients were treated successfully using endovascular
embolization without any complications. CONCLUSIONS: Endovascular therapy is
available and safe as a treatment option for distal lateral lenticulostriate
artery aneurysms.
PMID- 29959074
TI - Surgical Outcomes of Spinal Cord Intramedullary Cavernous Malformation: A
Retrospective Study of 83 Patients in a Single Center over a 12-Year Period.
AB - OBJECTIVE: Spinal cord intramedullary cavernous malformation (SICM) is kind of
rare vascular disease, and the therapeutic strategy is still under debate. The
purpose of this article is to analyze outcome of SICM surgical resection and to
find the possible factors indicating a better outcome. METHODS: A retrospective
analysis of 83 patients with SICM in a single center from 2005 to 2017 was
performed. Neurologic status was assessed using the McCormick Scale. Clinical
information was collected and analyzed using multivariate logistic regression
analysis. RESULTS: Eighty patients with SICM were included, 48% of whom were male
(n = 40). The mean age was 39.0 years; 7% of patients (n = 6) had a family
history and 4% of patients (n = 3) had multiple lesions; and 41% (n = 34) were
found with definite hemorrhage. Before surgery, neurologic status of the patients
was 43.4%, 31.3%, 13.3%, and 12.0% in grades I (n = 36), II (n = 26), III (n =
11), and IV (n = 10), respectively. Sixty-three patients received long-term
follow-up, of whom 19 improved, 39 remained in stable condition, and 5
deteriorated. Patients with duration of symptoms less than 3 months showed a
higher improved outcome rate than those with duration longer than 3 months.
CONCLUSIONS: The finding suggests that if total resection of SICM is achievable,
surgical therapy could be considered to avoid risks of severe complications
followed by lesion bleeding. Early microsurgical resection (usually within 3
months) for patients with SICM can lead to better clinical outcomes.
PMID- 29959075
TI - Full Recovery After a Bihemispheric Gunshot Wound to the Head: Case Report,
Clinical Management, and Literature Review.
AB - BACKGROUND: Nearly 33,600 people die each year in the United States as a result
of gunshot wounds (GSWs). Penetrating craniocerebral GSWs are often fatal with a
nearly 70% death rate at the scene of the trauma. Overall combined mortality rate
for patients who die at the scene or at the hospital is almost 91%. Poor outcome
is associated with initial low Glasgow Coma Scale score and bihemispheric and
transventricular gunshot trajectory. We summarize current understanding in
management, prognostic factors, and survival outcomes in patients with a
penetrating GSWs to the head. We report a patient with return to full function
despite bihemispheric, multilobar involvement. Full function is defined here as
ability to return to previous work and perform activities of daily living. CASE
DESCRIPTION: A 33-year-old man sustained a GSW to the head under unknown
circumstances. On initial presentation, he had a Glasgow Coma Scale score of 15.
He was verbalizing and communicating but was amnestic for the event. From a left
frontal entry wound, the bullet traversed both frontal lobes of the brain
reaching the right frontal-parietal junction. Physical examination and vital
signs were normal. Appropriate surgical and medical management resulted in
complete recovery. CONCLUSIONS: Craniocerebral GSWs have a high mortality rate
and usually require aggressive management. Evaluation of most GSWs requires
appropriate imaging studies followed by proactive treatment against infection,
seizure, and increased intracranial pressure. Surgical intervention is often
necessary and ranges from local wound debridement to craniectomy, decompression,
and wound exploration.
PMID- 29959076
TI - Development of Delayed Posttraumatic Acute Subdural Hematoma.
AB - BACKGROUND: Prior studies have shown that most patients with mild traumatic brain
injury or negative computed tomography (CT) scans of the head rarely decline or
require neurosurgical interventions. One common reason for a delayed decline is
an intracranial hemorrhage that presents within 24-48 hours. This is typically
seen in elderly patients and/or patients on antiplatelet or anticoagulation
agents. We describe a case of a delayed subdural hemorrhage presenting in a young
adult not on any antiplatelet or anticoagulation therapy. CASE DESCRIPTION: A 19
year-old male presented to the emergency department after being involved in a
motor vehicle accident. He had a Glasgow Coma Scale of 15, and an initial CT was
negative for any intracranial hemorrhage or pathology, so he was then admitted to
the intensive care unit for further care. The patient received 1 dose of aspirin
325 mg the following day for treatment of blunt cerebrovascular injury. Six hours
later he reported a severe headache and had an episode of emesis with a
subsequent rapid neurologic decline. Repeat CT showed an acute right subdural
hematoma, and he underwent an emergent right decompressive hemicraniectomy.
CONCLUSIONS: In rare cases, patients with negative initial head CT scans
neurologically deteriorate as a result of a delayed acute subdural hematoma. We
present an unusual case of a young patient on no medications with no CT findings
of an intracranial injury who neurologically declined due to a delayed acute
subdural hematoma.
PMID- 29959077
TI - Full Endoscopic Lumbar Discectomy using the Calcification Floating Technique for
Symptomatic Partially Calcified Lumbar Herniated Nucleus Pulposus.
AB - BACKGROUND: Partially calcified lumbar herniated nucleus pulposus (HNP) can cause
severe radiating pain and neurologic symptoms requiring surgical treatment. As it
is not safe to enforce conventional endoscopic lumbar discectomy using trephine
or burr to remove the partially calcified disc, we report a calcification
floating technique using a working channel for the treatment of these cases.
METHODS: We retrospectively analyzed 31 patients who underwent full endoscopic
discectomy using this technique for partially calcified lumbar HNP between April
2009 and June 2013. Calcification floating technique was performed by inserting
the working channel around the partially calcified HNP and then rotating the
working channel around it to remove the lesion. We analyzed the outcomes with a
Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and complication
rate. RESULTS: The mean follow-up period was 26.58 +/- 11.2 months. The
interlaminar approach was used in 15 cases, and the transforaminal approach was
used in 16 cases. The mean VAS of 8.19 +/- 0.65 before surgery was decreased to
1.29 +/- 0.69 at the last follow-up. The mean ODI score before surgery was
decreased at the last follow-up, from 41.32 +/- 2.87 to 9.87 +/- 3.47. Mean
operative duration was 45 +/- 12 minutes per level. None of the patients required
revision surgery or developed any major complication. CONCLUSIONS: Calcification
floating technique is a safe and effective method for the treatment of partially
calcified lumbar HNP.
PMID- 29959078
TI - Perioperative Measurement of Radiation Exposure to Radiation-Sensitive Organs of
Patients Undergoing Lumbar Surgeries Using a Thermoluminescent Dosimeter.
AB - OBJECTIVE: To introduce a method of accurately measuring the equivalent dose
received by radiation-sensitive organs using the thermoluminescent dosimeter
(TLD) and to provide reference values for future studies associated with
radiation protection in patients undergoing lumbar spine surgeries. METHODS:
After careful selection and preparation, TLD chips were used to obtain
measurements from the eyes, thyroid glands, breasts, and gonads of 20 patients
undergoing lumbar spine surgeries. The results were obtained via air kerma
conversion-related calculations. RESULTS: The overall radiation exposures
absorbed perioperatively by the eyes, thyroid glands, right breasts, left
breasts, right ovaries, left ovaries, and testes were 0.41 +/- 0.13, 1.43 +/-
0.45, 6.95 +/- 3.63, 9.50 +/- 6.14, 29.86 +/- 28.62, 23.47 +/- 22.10, and 5.41 +/
1.86 mSv, respectively. A single computed tomography (CT) scan contributed to
more than 75% of the overall dose received regardless of the position used.
CONCLUSIONS: Patients received significantly higher radiation doses from CT scans
than from regular digital radiograph examinations. These radiation doses were
concentrated in the regional area of scanning. Our results indicate the necessity
and benefits of radiation protection measures, especially for the organs
researched herein, when patients undergoing lumbar surgeries require radiographic
diagnostic examinations.
PMID- 29959079
TI - Exploratory Analysis into Reasonable Timeframes for the Provision of
Neurosurgical Care in Low- and Middle-Income Countries.
AB - BACKGROUND: In low- and middle-income countries (LMICs), 11.8% of the need for
neurosurgical care is met. Delays in seeking and receiving care may further
exacerbate this situation. Objective analysis of delay and its consequences is
contingent on reference to established resource-appropriate acceptable
timeframes. This study sought to 1) establish an estimate of the landscape of
care provided in LMICs and 2) explore reasonable timeframes for various stages of
patient-health care interaction. METHODS: Consensus input from neurosurgeons in
select LMICs was collected; 1 high-income country was included for comparison. In
phase 1, participants were asked to select neurosurgical procedures performed at
their centers. In phase 2, based on procedures shared among all LMICs,
representative case scenarios were generated and participants provided input on
acceptable timeframes for each stage of patient-health care interaction: 1)
presentation to health services, 2) diagnosis by primary care physician, 3)
referral to neurosurgical specialist care, and 4) definitive neurosurgical
management. RESULTS: Twenty neurosurgeons across 18 centers were identified; 12
participated in phase 1 and 7 in phase 2. The range of procedures offered was
broad, similar in scope to high-income countries, and included pediatric and
adult neurosurgery, trauma, degenerative spine, and hemorrhagic stroke.
Acceptable timeframes had wide ranges in certain cases; however, the overall
trend showed agreement between the participants. CONCLUSIONS: This exploratory
analysis identified reasonable timeframes for the provision of neurosurgical care
in LMICs. If validated, these data can be used to more objectively assess the
prevalence of delay in neurosurgical care in individual LMICs, along with its
consequences.
PMID- 29959080
TI - Trigeminal Neuralgia due to Vertebrobasilar Artery Compression.
AB - OBJECTIVE: Classical trigeminal neuralgia (cTN) is rarely caused by ectatic
vertebrobasilar artery compression of the trigeminal nerve. These patients
present a surgical challenge and often are not considered for microvascular
decompression (MVD) due to assumed risk. METHODS: A review of patients who were
surgically treated by the senior author between 1997 and 2016 with an admitting
diagnosis of cTN was performed. Details of the surgery were documented, including
the technique for maintaining vascular decompression, complications, and the
length of stay. Clinical follow-up was obtained from patient charts as well as
telephone questionnaires. RESULTS: During the 20-year review, 552 patients
underwent MVD for cTN, and 13 (2.4%) had dolichoectatic vertebrobasilar
compressions (10 male, 3 female). The average hospital length of stay was 2.8
days (range 2-7) with no major complications. At final follow-up (>2 years), 7
had no pain with no medications (78%), 2 had persistent pain (22%)-1 of whom
underwent a successful glycerol rhizotomy at 8 months-2 were lost to follow-up,
and 2 had surgery within 2 years. CONCLUSIONS: Patients with cTN due to a
dolichoectatic vertebrobasilar artery compression present a unique surgical
challenge. Mobilizing the vessel can be difficult because it may be firm from
atherosclerosis, maintaining its separation from the nerve is similarly
difficult, and manipulating the vessel can be dangerous because of its brainstem
perforators. Our case series provides some evidence to support the safety and
efficacy of MVD for patients with vertebrobasilar ectasia for those that major
surgery is not contraindicated.
PMID- 29959081
TI - Primary Solitary Intracranial Malignant Melanoma: A Systematic Review of
Literature.
AB - INTRODUCTION: Primary solitary intracranial malignant melanoma (PIMM) is
extremely rare. In 1992, an extensive review of 81 patients with PIMM was
undertaken. Imaging studies, microsurgery, and adjuvant therapy have developed
considerably over the last 25 years, and targeted therapy recently has been
proven successful for metastatic melanoma. These factors could influence current
and future clinical PIMM results. METHODS: We undertook a literature search of
PIMM patients since 1992. RESULTS: We reviewed 49 cases of PIMM. The mean age was
45.8 years. No significant sex difference was found. Intracranial hypertension
and focal neurologic deficits were commonly observed around 70% and 40%,
respectively. There were no significant differences of survival period according
to tumor sites. Surgeries were performed in 42 of 49 patients with PIMM reviewed
(92%). The mean survival of the gross total removal group was significantly
longer than that of surgical results (>22 months vs. 12 months (interquartile
range: 5-22 months; P = 0.026). For adjuvant therapy, 9 patients underwent
chemotherapy and 18 patients underwent radiotherapy postoperatively There was no
significant difference in survival period between with and without adjuvant
therapies. Leptomeningeal enhancement diagnosed in the initial MRI, was the worst
prognostic factor. CONCLUSIONS: Gross total removal of the PIMM was the most
promising treatment. Currently adjuvant therapy has not been associated with the
survival period. To improve clinical outcome, immunotherapy and targeted
therapies are likely to become more important.
PMID- 29959082
TI - Do Selected Blood Inflammatory Markers Combined with Radiological Features
Predict Proliferation Index in Glioma Patients?
AB - BACKGROUND: The tumor microenvironment is partially characterized by a state of
chronic inflammation, and radiologic features are related to the tumor's
biological behavior. This study was conducted to explore whether peripheral blood
inflammatory markers combined with radiologic features could predict
proliferation potency. METHODS: This study retrospectively reviewed 183 patients
with a primary diagnosis of glioma. Clinical characteristics, preoperative
peripheral full blood count data, and brain magnetic resonance imaging findings
were reviewed to analyze the expression of inflammatory markers neutrophil
lymphocyte ratio (NLR), monocyte lymphocyte ratio, and platelet lymphocyte ratio
(PLR), as well as radiologic features such as location, peritumor edema, and
contrast enhancement. Immunohistochemical staining was performed to determine the
proliferation index (i.e., expression of Ki-67). Receiver operating
characteristic curves for cutoff value, various bivariate tests, and binary
logistic regression analyses were applied. RESULTS: Proliferation index was
highly associated with tumor grade, showing a gradually increasing tendency. A Ki
67 cutoff value >9% predicted high-grade glioma (HGG). Mean NLR and PLR were
significantly higher in the HGG group compared with the low-grade glioma group
(NLR: 3.11 +/- 0.59 vs. 4.27 +/- 1.13; PLR: 133.07 +/- 13.17 vs. 161.51 +/-
38.99; P < 0.01 for both). Contrast enhancement was more likely in the HGG group,
but there was no significant between-group difference in peritumor edema.
Logistic regression analysis identified the following risk factors for prediction
of proliferation potency: age, Karnofsky Performance Score, NLR, PLR, and
contrast enhancement. However, age >43 years, NLR >3.68, and positive contrast
enhancement independently predicted a higher proliferation rate. CONCLUSIONS: NLR
and contrast enhancement were positively correlated with the proliferation
potency of gliomas.
PMID- 29959083
TI - Circulating tumor cells: Screening and monitoring of oral cancers.
PMID- 29959084
TI - Serum responsive proteome reveals correlation between oxidative phosphorylation
and morphogenesis in Candida albicans ATCC10231.
AB - : To understand the impact of fetal bovine serum (FBS) on metabolism and cellular
architecture in addition to morphogenesis, we have identified FBS responsive
proteome of Candida albicans. FBS induced 34% hyphae and 60% pseudohyphae in C.
albicans at 30 degrees C while 98% hyphae at 37 degrees C. LC-MS/MS analysis
revealed that 285 proteins modulated significantly in response to FBS at 30
degrees C and 37 degrees C. Out of which 152 were upregulated and 62 were
downregulated at 30 degrees C while 18 were up and 53 were downregulated at 37
degrees C. Functional annotation suggests that FBS may inhibit glycolysis and
fermentative pathway and enhance oxidative phosphorylation (OxPhos), TCA cycle,
amino acid and fatty acid metabolism indicating a use of alternative energy
source by C. albicans. OxPhos inhibition assay using sodium azide corroborated
the correlation between inhibition of glycolysis and enhanced OxPhos with
pseudohyphae formation. C. albicans induced hyphae in response to FBS
irrespective of down regulation of Ras1,Asr1/Asr2, indicates the possible
involvement of MAPK and cAMP-PKA independent pathway. The Cell wall of cells
grown in presence of FBS at 30 degrees C was rich in mannan, Beta 1,3-glucan and
chitin while membranes were rich in ergosterol compared to those grown at 37
degrees C. SIGNIFICANCE OF THE STUDY: This is the first study suggesting a
correlation between OxPhos and morphogenesis especially pseudohyphae formation in
C. albicans. Our data also indicate that fetal bovine serum (FBS) induced
morphogenesis is multifactorial and may involve MAPK and cAMP-PKA independent
pathway. In addition to morphogenesis, our study provides an insight in to the
modulation of metabolism and cellular architecture of C. albicans in response to
FBS.
PMID- 29959085
TI - "In the Clinic They Know Us": Preferences for Clinic-Based Financial and
Employment Services in Urban Pediatric Primary Care.
AB - OBJECTIVE: To understand views of adolescent and adult caregivers on integrating
employment and financial services into a pediatric primary care clinic serving
low-income families. METHODS: Eighteen in-depth qualitative interviews were
conducted among caregivers of pediatric patients. Participants were recruited
from those who completed a survey assessing financial and employment needs. Audio
recorded transcripts were analyzed using line-by-line coding of emerging themes.
RESULTS: Adolescent and adult caregivers expressed difficulty managing financial
stress. They cited having a criminal history, limited financial literacy, and
lack of available quality jobs as barriers to achieving financial stability. A
clinic-based employment and financial program was highly acceptable among
potential users for the convenience it offers and the established trust and
understanding between patients and clinical providers. Participants preferred one
on-one counseling for sensitive employment and financial issues, although they
did believe that some topics, such as building a resume, could be accomplished in
group workshops. CONCLUSIONS: Caregivers attending a pediatric clinic expressed
interest in and anticipated value from clinic-based employment and financial
services if implemented services are relevant, accessible, and provide options
for group and individualized approaches.
PMID- 29959086
TI - Management and prognosis of pure primary squamous cell carcinoma of the breast.
AB - PURPOSE: The aim of the study was to investigate the management and prognosis of
Pure primary squamous cell carcinoma (PPSCC) of the breast. MATERIALS AND
METHODS: This study is a multicentre retrospective cohort from three French
tertiary referral hospitals (Rennes, Orleans and Tours) including all women
treated for a PPSCC of the breast defined by squamous cells that could contain a
minority of sarcomatoid component. We excluded carcinomas with a ductual
component. Clinicopathologic, radiological and therapeutic patterns were
described. Demographic, histological and therapeutic characteristics were
compared to a population of women with triple negative invasive breast
carcinomas. RESULTS: Twelve patients were included, with a mean age of 71.6
years. All lesions were unifocal, with a cystic complex ultrasound mass in 50% of
cases. Mean tumor size was 43mm, with axillary lymph node metastasis in 25% of
patients. The comparison with a population of women with triple negative breast
carcinomas revealed that women with PPSCC were older (71 versus 57 years,
p=0.003), tumor size was larger (43mm versus 25mm, p=0.032) and local recurrence
occurred earlier (three months versus 38 months, p=0.014). CONCLUSION: PPSCC is a
rare entity with a worse prognosis in comparison with triple negative invasive
carcinoma.
PMID- 29959087
TI - Healthcare itinerary of women undergoing an abortion according to their
vulnerability.
AB - CONTEXT: Precariousness is increasing among all populations and especially among
women. The access to healthcare is increasingly unequal upon the population and
particularly in access to contraception methods or abortion according to their
vulnerability level. OBJECTIVE: Our main object is to describe the socio
demographic specifications, the different steps involved in the healthcare
itinerary to contraception and abortion, according to the level of social
vulnerability for a woman population sample requesting an abortion. The secondary
objects are to detect the existence of a difficult healthcare itinerary and to
describe the exposure to risky situations or behaviors according to their
vulnerability level. METHOD: It is an observational cross-sectional survey to
women having recourse to induced abortion in centers providing them, during 3
month in 2014, in the Aquitaine area. The validated tool to evaluate this
situation in a psycho-social approach is the "EPICES score". RESULTS: Our sample
identifies 49% of women in a precariousness situation. These women are younger
and more often less employed. They benefit less often from a regular gynecology
follow-up, do not use contraception as often and resort to abortion more often.
They relate more often risky behavior for the health, conflict with the partner
and psychological, physical violence. CONCLUSION: Special attention should be
brought to all women in request of an abortion, for half of them are in a
precarious situation and this physical might be a rare occasion of access to
healthcare. Violence screening should be systematic and the choice of a long term
birth control method should be encouraged.
PMID- 29959088
TI - Characterization of the suspension stability of pharmaceuticals using a
shadowgraphic imaging method.
AB - A new shadowgraphic imaging method and an associated instrument for analyzing the
physical stability of pharmaceutical suspensions are introduced in this paper.
The new suspension tester consists mainly of a high-resolution camera that takes
sequential shadowgraphic images of emulsions or suspensions and a 2D collimated
LED for simultaneous whole-sample illumination in bright field. A built-in
ultrasonic bath provides controlled initial agitation to the samples of interest.
Sequential images acquired by the experimental setup were used to derive
normalized transmission profiles from which an instability index was developed
for quantitative stability comparison between samples. Instrument performance was
verified by measuring the stability of a series of oil-in-water emulsions
prepared with surfactant mixtures of different ratios. The new instrument
correctly determined the required hydrophilic-lipophilic balance for sunflower
oil to be 7.0. The stability of a pressurized suspension of spray dried lipid
(DSPC) particles was monitored for 5 days after propellant filling. Although
stable for the first 24 h, the lipid suspension was found to decrease in
stability from day 1 to day 4. Morphological and spectroscopic analysis revealed
that the suspended DSPC particles had reformed into large thin sheets of lipid,
thereby causing the gradual stability decrease during the aging study. The
effects of initial agitation on the stability of suspensions were demonstrated by
agitating a suspension of micronized fluticasone propionate in propellant using a
wrist action shaker and an ultrasonic bath respectively. A significant
improvement of suspension stability was achieved by replacing the wrist action
shaker method with ultrasonic agitation. Simultaneous illumination of the
complete suspension, a high image acquisition rate, and controlled initial
agitation are features that make this new suspension tester a suitable and more
reliable instrument for investigating the stability of pressurized pharmaceutical
suspensions.
PMID- 29959089
TI - In situ fabrication of mesoporous silica-coated silver-gold hollow nanoshell for
remotely controllable chemo-photothermal therapy via phase-change molecule as
gatekeepers.
AB - This study reports a new strategy for in situ fabrication of plasmonic hollow
silver-gold nanoshell (with resonance tuned to NIR region) encased in the hollow
mesoporous silica as an efficient platform to efficiently and precisely regulate
the release of 5-fluorouracil (anticancer drug) for prostate cancer therapy and
photothermal therapy. The mesopores were capped with thermosensitive phase-change
material lauric acid, which allowed for remote, precise, and spatiotemporal
control of drug release via external heating or photothermal heating of plasmonic
silver-gold nanoshell via NIR laser irradiation. The system was nanometric,
monodispersed, and showed negative surface charge. The nanocarrier showed better
pH stability and thermodynamic stability compared to dense silica-coated gold
nanoshells. The drug release could be triggered remotely by applying low powered
continuous wave NIR laser (lambda = 808 nm). The nanocarrier showed improved
internalization by cancer cells, which was further enhanced by laser irradiation.
High powered laser directly killed the cancer cells via photothermal effect in
the region irradiated. Thus, this system fabricated by novel synthetic strategy
provided efficient chemo- and phototherapy.
PMID- 29959090
TI - Dermal delivery of Fe-chlorophyllin via ultradeformable nanovesicles for
photodynamic therapy in melanoma animal model.
AB - Melanoma is resistant to chemotherapeutics with poor prognosis and high potential
of metastasis. Photodynamic therapy (PDT) represents a localized therapeutic
modality, as cytotoxicity occurs when light activates photosensitizer (PS) at the
tumour site. The aim of this study is dermal delivery of a high molecular weight
hydrophilic photosensitizer (PS), ferrous chlorophyllin (Fe-CHL) via
transethosomes for treatment of melanoma by PDT. Transethosomes were made of
phosphatidyl choline, edge activator and 20% w/v Ethanol. They were evaluated for
mean size, zeta potential, entrapment efficiency, ex-vivo permeation,
localization in skin layers by transmission electron microscope (TEM), and
finally, evaluated in melanoma animal model. Transethosomes of different mean
vesicle size were evaluated for their skin retention and permeation through mice
skin. TE of ~500 nm (E3) being ultradeformable showed deep localization in skin
confirmed by ex-vivo and TEM micrographs without permeation of PS to recipient
compartment due to its size. The proposed study offers successful treatment of
resistant melanoma by PDT, where complete tumour regression of small tumours
occurred after single PDT, while large tumours after double PDT without
recurrence for 8 months. This indicates the efficiency of nanovesicles in PS
delivery and the efficiency of Fe-CHL in production of reactive oxygen species.
PMID- 29959091
TI - Asian citrus psyllid stylet morphology and applicability to the model for inter
instar stylet replacement in the potato psyllid.
AB - In Hemiptera, presumptive stylets for each consecutive postembryonic instar are
manufactured prior to ecdysis to replace the ecdysial stylets discarded with the
exuviae. With the discovery that the bacterium "Candidatus" Liberibacter
solanacearum accesses the tissues involved in the stylet replacement process of
the potato psyllid, a hypothesis was formed that the bacterium could adhere to
the stylets of freshly emerged instars and hence gain access to the host plant
when feeding is resumed. Although unproven, it was imperative that a model for
stylet replacement be built. Stylet morphology and the stylet replacement process
of the Asian citrus psyllid (ACP), vector of "C." L. asiaticus, causal pathogen
of citrus greening disease, are comparable to the potato psyllid model system.
Morphology consists of a basal terminus with its tab-shaped auricle, a base,
shaft, and an apical terminus. Each of the four auricles act as a platform for
the replacement apparatus, which is compacted into a tight aggregate of cells,
the 'end-cap'. As modeled, on apolysis of larval instar hypodermis, the aggregate
'deconstructs' and expands into a snail shell-shaped tube, the 'atrium', that
houses the presumptive stylet as it is synthesized. Completed stylets then
despool from the atrium and are fitted into their functional positions as the
next instar emerges from its exuviae.
PMID- 29959092
TI - Identification of the antigenic region of Neospora caninum dense granule protein
7 using ELISA.
AB - Dense granule protein 7 (NcGRA7) is a potent diagnostic antigen of Neospora
caninum. Some studies have reported on the difficult expression, low yield, and
variable degree of solubility of recombinant NcGRA7. We aimed to unravel the
possible causes for these issues and tested NcGRA7 antigenicity in enzyme linked
immunosorbent assays (ELISAs). The NcGRA7 coding sequence (217 amino acids) was
split into five amino acid regions: NcGRA7m (27-217), NcGRA7m3 (27-160), NcGRA7m4
(27-135), NcGRA7m5 (161-190), and NcGRA7m6 (188-217). Three fragments, NcGRA7m,
NcGRA7m3 and NcGRA7m4, exhibited high antigenic properties when tested against
experimentally-infected mice and dog sera by ELISA. High levels of IgG2
antibodies against NcGRA7m3 were observed in field dog sera. In experimentally
and naturally-infected cattle, the N. caninum-specific sera only reacted with
NcGRA7m, indicating that this antigenic region differs among the three animal
species. This study presents valuable information about the antigenic properties
and topology of NcGRA7, and highlights its suitability for diagnostic purposes.
PMID- 29959093
TI - Molecular survey and characterization of Theileria annulata and Ehrlichia
ruminantium in cattle from Northwest China.
AB - Theileriosis and ehrlichiosis are two important tick-borne diseases affecting
cattle farming in China. However, limited information is available regarding
prevalence and molecular characterization of Theileria annulata and Ehrlichia
ruminantium in cattle in Xinjiang Uygur Autonomous Region (XUAR), northwestern
China. In this study, a total of 176 blood samples of cattle from three rural
areas of XUAR were collected in June 2017 and were tested by nested-PCR. A total
of 34 (19.3%) samples were found to be infected with one or two pathogens. The
overall prevalence rates of T. annulata and E. ruminantium were 18.2% and 1.7%,
respectively. Phylogenetic analyses revealed that the E. ruminantium isolates
from XUAR were located in the same clade but diverged from the isolates from
African countries using pCS20 gene while T. annulata isolates from XUAR revealed
differences in the genotypes using Tams1 sequences. To our knowledge, this is the
first report of E. ruminantium infection in cattle in China. It also provides the
first genetic characterization of T. annulata in cattle in XUAR. The current
findings are important for understanding the distribution of agents of
theileriosis and ehrlichiosis and in designing measures for the prevention and
control of tick-borne diseases in cattle, other animals, and humans.
PMID- 29959094
TI - Neonatal meningitis and recurrent bacteremia with group B Streptococcus
transmitted by own mother's milk: A case report and review of previous cases.
AB - This article reports a case of neonatal meningitis and recurrent bacteremia
caused by group B Streptococcus (GBS) transmitted via the mother's milk. A 3-day
old neonate suffered early-onset meningitis due to GBS, from which he recovered
after antibiotic treatment for 4 weeks. GBS was not detected in the vaginal or
stool cultures of the neonate's mother before delivery. However, 4days after
treatment of GBS meningitis, the neonate developed GBS bacteremia. As the mother
repeatedly showed signs of mastitis after the delivery, bacterial culture tests
were performed on her breast milk, in addition to vaginal and stool culture
tests. GBS was exclusively detected in the mother's breast milk. The GBS strains
detected in the cerebrospinal fluid of the neonate and the mother's breast milk
were both serotype III, and were confirmed to be identical through pulsed-field
gel electrophoresis analysis. As horizontal GBS transmission between the mother
and neonate was indicated, breastfeeding was ceased and replaced with formula
milk. No recurrence of bacterial meningitis or bacteremia due to GBS was observed
thereafter. Physicians need to consider culturing breast milk in cases of
recurrent neonatal GBS infections, even in mothers without prior detection of GBS
in conventional vaginal or stool cultures before delivery.
PMID- 29959095
TI - From hidden outbreaks to epidemic emergencies: the threat associated with
neglecting emerging pathogens.
AB - Not all infectious disease outbreaks undergo full epidemiological investigations.
In certain situations, the resultant lack of knowledge has led to the development
of epidemics and public health emergencies. This review will examine six emerging
pathogens including their history, present status, and potential to expand to
epidemics. Recommendations to improve our understanding of these hidden outbreaks
and others also will be provided in the context of health systems policy.
PMID- 29959096
TI - Chlamydial plasmid-encoded virulence factor Pgp3 interacts with human
cathelicidin peptide LL-37 to modulate immune response.
AB - We have previously reported that Chlamydia trachomatis plasmid-encoded Pgp3 is
able to neutralize anti-chlamydial activity of human cathelicidin peptide LL-37
by binding to and forming stable complex with LL-37. Besides its microbicidal
activity, LL-37 also modulates immune response, including inducing
cytokine/chemokine production in fibroblast/epithelial cells and recruitment of
inflammatory cells. We now report that LL-37 was significantly induced in the
genital tracts of women diagnosed positive for C. trachomatis. Both the LL-37
stimulated IL-6/8 production in human endometrial epithelial cells and the LL-37
induced neutrophil chemotaxis were blocked by Pgp3. Interestingly, although Pgp3
itself alone could not induce cytokines in epithelial cell cells, it did so in
neutrophils. Importantly, the Pgp3 proinflammatory activity in neutrophils was
significantly enhanced by forming complex with LL-37 although LL-37 alone failed
to induce cytokine production in neutrophils. Thus, we have demonstrated that
Pgp3 can modulate the proinflammatory activities of LL-37 on epithelial cells by
forming stable complex with LL-37 but the Pgp3's own proinflammatory activity on
myeloid cells is enhanced by forming the same complex. We hypothesize that
Chlamydia may use Pgp3 to both block detrimental inflammation for improving its
own fitness in the genital tract epithelial tissue and activate myeloid cell
mediated inflammation for potentially promoting spreading between the hosts, the
latter of which may inevitably contribute to the development of inflammatory
sequelae such as tubal fibrosis.
PMID- 29959097
TI - Sagittal spinal alignment deviation in the general elderly population: a Japanese
cohort survey randomly sampled from a basic resident registry.
AB - BACKGROUND CONTEXT: It is widely recognized that sagittal spinal alignment
changes with age. However, there are presently no clear benchmarks for such
values or those for the cervical spine in the general population. Quality
epidemiological studies are needed to establish standards for spinal alignment
deviation. OBJECTIVES: In this study of an aged Japanese population, we employed
random sampling from the basic resident registry of a rural town for subject
selection to determine reference values of sagittal spinal alignment including
the cervical spine. STUDY DESIGN: Japanese resident cohort study based on a
municipal registry. PATIENT SAMPLE: A total of 413 aged people randomly sampled
from the resident registry of a rural Japanese town. OUTCOME MEASURES: All
subjects underwent a whole spine lateral radiograph for measurement of sagittal
spinal alignment parameters. METHODS: Registered citizens of 50 to 89years old
were targeted for this survey. We established eight groups based on age (50s,
60s, 70s, and 80s) and gender (male and female) after random sampling from the
resident registry of Obuse town in 2014. A total of 413 people (203 males and 210
females) were enrolled. Radiographic parameters of sagittal spinal alignment of
the cohort were measured and analyzed. Funding for this study was provided by the
Japan Orthopaedics and Traumatology Research Foundation (10,000 USD), the
Japanese Orthopaedic Association (5,000 USD), the Japanese Society for
Musculoskeletal Medicine (40,000 USD), and the Nakatomi Foundation (15,000 USD).
RESULTS: Global spinal alignments became more misaligned with age for both
genders. Sagittal vertical axis (SVA) forward shift was significantly more
frequent in 80s males and 70s females, and SVA in 80s females was a mean of 66mm
forward of that of 50s females. Cervical protrusion was markedly greater in 60s
males onwards. In women, lumbar lordosis and posterior pelvic inclination were
noticeable from a younger age than in men. The amount of pelvic tilt misalignment
in female subjects was approximately 10years earlier than their male
counterparts. CONCLUSIONS: This first resident cohort of Japanese individuals
determined average spinal alignment parameters by age and gender. Spinal balance
generally shifts forward as age increases. A forward shift in the upper cervical
spine occurs first in men, whereas lumbopelvic alignment shift occurs first in
women.
PMID- 29959098
TI - Lumbar epidural steroid injections for herniation and stenosis: incidence and
risk factors of subsequent surgery.
AB - BACKGROUND CONTEXT: Lumbosacral epidural steroid injections (ESIs) have increased
dramatically despite a narrowing of the clinical indications for use. One
potential indication is to avoid or delay surgery, yet little information exists
regarding surgery rates after ESI. PURPOSE: The purpose of this research was to
determine the proportion of patients having surgeryafter lumbar ESI for disc
herniation or stenosis and to identify the timing and factors associated with
this progression. STUDY DESIGN/SETTING: This study was a retrospective review of
nationally representative administrative claims data from the Truven Health
MarketScan databases from 2007 to 2014. PATIENT SAMPLE: The study cohort was
comprised of 179,025 patients (54+/-15years, 48% women) having lumbar ESIs for
diagnoses of stenosis and/or herniation. OUTCOME MEASURES: The primary outcome
measure was the time from ESI to surgery. METHODS: Inclusion criteria were ESI
for stenosis and/or herniation, age >=18years, and health plan enrollment for 1
year before ESI to screen for exclusions. Patients were followed longitudinally
until they progressed to surgery or had a lapse in enrollment, at which time they
were censored. Rates of surgery were assessed with the Kaplan-Meier survival
curves. Demographic and treatment factors associated with surgery were assessed
with multivariable Cox proportional hazard models. No external funding was
procured for this research and the authors' conflicts of interest are not
pertinent to the present work. RESULTS: Within 6 months, 12.5% of ESI patients
underwent lumbar surgery. By 1 year, 16.9% had surgery, and by 5 years, 26.1% had
surgery. Patients with herniation had surgery at rates of up to five-fold to
seven-fold higher, with the highest rates of surgery in younger patients and
those with both herniation and stenosis. Other concomitant spine diagnoses, male
sex, previous tobacco use, and residence a rural areas or regions other than the
Northeastern United States were associated with higher surgery rates. Medical
comorbidities (previous treatment for drug use, congestive heart failure,
obesity, chronic obstructive pulmonary disease, hypercholesterolemia, and other
cardiac complications) were associated with lower surgery rates. CONCLUSIONS: In
the long term, more than one out of every four patients undergoing ESI for lumbar
herniation or stenosis subsequently had surgery, and nearly one of six had
surgery within the first year. After adjusting for other patient demographics and
comorbidities, patients with herniation were more likely have surgery than those
with stenosis. The improved understanding of the progression from lumbar ESI to
surgery will help to better inform discussions regarding the value of ESI and aid
in the shared decision-making process.
PMID- 29959099
TI - Risk Factors for Newly Developed Osteoporotic Vertebral Compression Fractures
Following Treatment for Osteoporotic Vertebral Compression Fractures.
AB - BACKGROUND CONTEXT: It has been reported that newly developed osteoporotic
vertebral compression fractures (OVCFs) occur at a relatively high frequency
after treatment. While there are many reports on possible risk factors, these
have not yet been clearly established. PURPOSE: The purpose of this study was to
investigate the risk factors for newly developed OVCFs after treatment by
vertebroplasty (VP), kyphoplasty (KP), or conservative treatment. STUDY
DESIGN/SETTING: A retrospective comparative study. PATIENT SAMPLE: One hundred
thirty-two patients who had radiographic follow-up data for one year or longer
among 356 patients who were diagnosed with OVCF and underwent VP, KP or
conservative treatment between March 2007 and February 2016. OUTCOME MEASURES:
All records were examined for age, sex, body mass index (BMI), rheumatoid
arthritis (RA) and other medical comorbidities, osteoporosis medication, bone
mineral density (BMD), history of vertebral and non-vertebral fractures,
treatment methods used, level of fractures, and presence of multiple fracture
sites. METHODS: Patients were divided into those who manifested new OVCF (Group
A) and those who did not (Group B). For the risk factor analysis, student's t
tests and chi-square tests were used in univariate analysis. Multivariate
logistic regression analysis was carried out on variables with a p<0.1 in the
univariate analysis. RESULTS: Newly developed OVCFs occurred in 46 of the 132
patients (34.8%). Newly developed OVCF increased significantly with factors such
as average age (p=0.047), low BMD T-score of the lumbar spine (p=0.04) and of the
femoral neck (p=0.046), advanced age (>70 years) (p=0.011), treatment by cement
augmentation (p=0.047) and low compliance with osteoporosis medication (p=0.029).
In multivariate regression analysis, BMD T-score of the lumbar spine (p=0.009)
and treatment by cement augmentation (p=0.044) showed significant correlations
with the occurrence of new OVCFs with a predictability of 71.4%. CONCLUSION: OVCF
patients with low BMD T-score of the lumbar spine and those who have been treated
by cement augmentation have an increased risk of new OVCFs after treatment and,
therefore, require especially careful observation and attention.
PMID- 29959100
TI - Preoperative severity of facet joint degeneration does not impact the 2-year
clinical outcomes and cervical imbalance following laminoplasty.
AB - BACKGROUND CONTEXT: The impact of preoperative facet degeneration (FD) on
surgical outcomes following laminoplasty has not been established. PURPOSE: To
elucidate the influence of preoperative FD on pre and postoperative clinical
symptoms and radiographic parameters. STUDY DESIGN: Retrospective analysis of
prospectively collected data. PATIENT SAMPLE: A total of 135 consecutive patients
who underwent laminoplasty for cervical spondylotic myelopathy with greater than
2years follow-up. OUTCOME MEASURES: The cervical Japanese Orthopedic Association
score, visual analog scale, Short Form-36, Japanese Orthopedic Association
Cervical Myelopathy Evaluation Questionnaire, and radiographic parameters (C7
slope, C2-C7 sagittal vertical axis, C2-C7 lordotic angle, and scoring of FD).
METHODS: FD severity of the bilateral facets of C2-3 to C7-T1 was graded using
preoperative computer tomography images. Patients were divided into two quantiles
according to the mean score of their FD grading: mild (n=69) and severe FD groups
(n=66). The preoperative clinical score and radiographic parameters of the two
groups were compared. Variables with p<.05 were included in the multinomial
logistic regression model. The changes in clinical scores and radiographic
parameters between both groups (from the preoperative to 2-year postoperative
period) were compared using a mixed-effect model, after adjusting for age and
sex. RESULTS: Mean age and neck pain visual analog scale were independently
associated with FD severity (age: p=.004, neck pain: p=.004). However, the other
preoperative clinical scores and radiographic parameters were not significantly
different. In terms of the change in clinical scores 2years postlaminoplasty, no
significant differences between the severe and mild FD groups were noted. While
the mild FD group had a reduced C2-C7 lordotic angle, the severe FD group
demonstrated an increased C2-C7 lordotic angle 2years postlaminoplasty (p=.044).
The change in C7 slope and C2-C7 sagittal vertical axis showed no significant
differences. CONCLUSIONS: Preoperative FD severity did not influence the 2-year
surgical outcomes of laminoplasty, in terms of improvement in myelopathy, patient
oriented score of quality of life, physical and mental status, as well as neck
pain. Furthermore, preoperative FD severity correlated with neither preoperative
cervical imbalance nor balance deterioration after laminoplasty. These results
may encourage physicians to consider laminoplasty for patients with cervical
spondylotic myelopathy, regardless of the severity of FD.
PMID- 29959101
TI - Value of standard radiographs, computed tomography, and magnetic resonance
imaging of the lumbar spine in detection of intraoperatively confirmed pedicle
screw loosening-a prospective clinical trial.
AB - BACKGROUND CONTEXT: Pedicle screw loosening is common after spinal fusion and can
be associated with pseudoarthrosis and pain. With suspicion of screw loosening on
standard radiographs, CT is currently considered the advanced imaging modality of
choice. MRI with new metal artifact reduction techniques holds potential to be
sensitive in detection of screw loosening. The sensitivity and specificity of
either of the imaging modalities are yet clear. PURPOSE: To evaluate the
sensitivity and specificity of three different image modalities (standard
radiographs, CT, and MRI) for detection of pedicle screw loosening. STUDY
DESIGN/SETTING: Cross-sectional diagnostic study. PATIENT SAMPLE: Forty-one
patients (159 pedicle screws) undergoing revision surgeries after lumbar spinal
fusion between August 2014 and April 2017 with preoperative radiographs, CT, and
MRI with spinal metal artifact reduction (STIR WARP and TSE high bandwidth
sequences). OUTCOME MEASURES: Sensitivity and specificity in detection of screw
loosening for each imaging modality. METHODS: Screw torque force was measured
intraoperatively and compared with preoperative screw loosening signs such as
peri-screw edema in MRI and peri-screw osteolysis in CT and radiographs. A torque
force of less than 60 Ncm was used to define a screw as loosened. RESULTS:
Sensitivity and specificity in detection of screw loosening was 43.9% and 92.1%
for MRI, 64.8% and 96.7% for CT, and 54.2% and 83.5% for standard radiographs,
respectively. CONCLUSIONS: Despite improvement of MRI with metal artifact
reduction MRI technique, CT remains the modality of choice. Even so, CT fails to
detect all loosened pedicle screws.
PMID- 29959102
TI - Sensitivity and specificity of patient-entered red flags for lower back pain.
AB - BACKGROUND CONTEXT: Red flags are questions typically ascertained by providers to
screen for serious underlying spinal pathologies. The utility of patient-reported
red flags in guiding clinical decision-making for spine care, however, has not
been studied. PURPOSE: The aim of this study was to quantify the sensitivity and
specificity of patient-reported red flags in predicting the presence of serious
spinal pathologies. STUDY DESIGN: This was a retrospective nested case-control
study. PATIENT SAMPLE: This study consisted of 120 patients with International
Classification of Diseases, Ninth Revision, Clinical Modification codes for
spinal pathologies and 380 randomly selected patients, from a population of 4,313
patients seen at a large tertiary care spine clinic between October 9, 2013 and
June 30, 2014. OUTCOME MEASURES: The presence of patient-reported red flags and
red flags obtained from medical records was verified for chart review. The spinal
pathology (ie, malignancy, fractures, infections, or cauda equina syndrome) was
noted for each patient. METHODS: The sensitivity and specificity of patient
reported red flags for detecting serious spinal pathologies were calculated from
data obtained from the 500 patients. Youden's J was used to rank performance.
Agreement between patient-reported red flags and those obtained from medical
record review was assessed via Cohen's kappa statistic. RESULTS: "History of
cancer" was the best performing patient-reported red flag to identify malignancy
(sensitivity=0.75 [95% confidence intervals, CI 0.53-0.90], specificity=0.79 [95%
CI 0.75-0.82]). The best performing patient-reported red flag for fractures was
the presence of at least one of the following: "Osteoporosis," "Steroid use," and
"Trauma" (sensitivity=0.59 [95% CI 0.44-0.72], specificity=0.65 [95% CI 0.60
0.69]). The prevalence of infection and cauda equina diagnoses was insufficient
to gauge sensitivity and specificity. Red flags from medical records had better
performance than patient-reported red flags. There was poor agreement between
patient red flags and those obtained from medical record review. CONCLUSIONS:
Patient-reported red flags had low sensitivity and specificity for identification
of serious pathologies. They should not be used in insolation to make treatment
decisions, although they may be useful to prompt further probing to determine if
additional investigation is warranted.
PMID- 29959103
TI - Radiographic methods to estimate surgical outcomes based on spinal flexibility
assessment in patients who have adolescent idiopathic scoliosis: A systematic
review.
AB - BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) is a three-dimensional
deformity recognized with lateral curvature of the spine as well as axial
vertebral rotation. Surgical interventions are recommended when patients with AIS
have severe curvature (Cobb angle >45o). Spinal flexibility is one of important
parameters for surgeons to plan surgical treatment. Few radiographic methods have
been developed to assess spinal flexibility. PURPOSE: A systematic review was
performed to evaluate which preoperative radiographic methods should be used to
estimate spinal flexibility based on the postoperative outcomes. STUDY DESIGN:
Studies which included any of the five radiographic methods: (1) supine side
bending (SBR), (2) fulcrum-bending (FBR), (3) traction, (4) push-prone, and (5)
suspension were reviewed and compared to determine which method provided the most
accurate estimation of the postoperative outcomes. PATIENT SAMPLE: Seven case
series, one case control, and multiple cohort studies reported the flexibility
assessment methods with the estimations of postoperative outcomes on patients
with AIS. OUTCOME MEASURES: The flexibility index defined as a correction rate
relative to flexibility rate was used to estimate the immediate and final follow
up postoperative outcomes. METHODS: Seven databases searched included MEDLINE,
CENTRAL, EMBASE, CINAHL, Web of Science, LILACS, and Google Scholar. Three
independent reviewers were involved for abstracts and full-texts screening as
well as data extraction. The Quality in Prognostic Studies quality appraisal tool
was used to assess the risk of bias within the studies. Also, the GRADE system
rate was used to assess the evidence level across the studies. RESULTS: Forty-six
articles were included. The distribution of the five flexibility methods in these
46 studies were SBR 38/46 (83%), fulcrum bending radiograph (FBR) 16/46 (35%),
traction radiograph 5/46 (11%), push-prone 1/46 (2%), and suspension 1/46 (2%).
Based on the overall assessment of flexibility indices, FBR had the best
estimation of postoperative correction among the five methods. FBR method
provided the best estimations of immediate and final follow-up postoperative
outcomes for moderate (25 degrees -45 degrees ) and severe (>45 degrees ) curves,
respectively. For main thoracic and thoracolumbar/lumbar curves, the best
estimations were traction, and FBR. However, in the reviewed articles, the risk
of bias was rated moderate and the quality of evidence was rated very low to low
so that a strong conclusive statement cannot be made. CONCLUSIONS: SBR method was
the most commonly used method to assess the spinal flexibility. The FBR method
was the most accurate method to estimate the postoperative outcomes based on the
limited evidence of the 46 articles.
PMID- 29959104
TI - Trial-level prediction of long-term outcome based on pathologic complete response
(pCR) after neoadjuvant chemotherapy for early-stage breast cancer (EBC).
AB - BACKGROUND: The US Food and Drug Administration and European Medicines Agency
have published guidance for industry on the use of pathologic complete response
(pCR) as a surrogate endpoint to accelerate the regulatory approval of
neoadjuvant agents in high-risk early-stage breast cancer (EBC). Three meta
analyses, the CTNeoBC consortium (Cortazar 2014), Berruti (2014), and Korn
(2016), evaluated the association between the pCR odds ratio and the event
hazards ratio but did not identify strong trial-level associations. Thus,
uncertainties remain with respect to whether the magnitude of effect-size
increase in pCR reasonably predicts long-term clinical benefit. FINDINGS: Trial
level data from CTNeoBC were used as the training data set to derive an empirical
nonlinear model for predicting long-term outcomes based on pCR results. A Cox
regression model was used to evaluate the relationship among treatments, event
hazards, and pCR as joint covariates. The trial-level association between
treatment and event hazard was derived and then linked with pCR rates. Magnitude
of the patient-level association was also included in the analysis. Additional
published trials were used to validate the predictive model. Numerical
differences between the perfect surrogate prediction and observed effect followed
normal distribution based on the Kolmogorov-Smirnov test. For event-free survival
(EFS), the Student t-test P value of 0.02 suggested a statistically significant
nonzero difference, with a mean value of -0.163 (SE 0.058). For overall survival
(OS), the Student t-test P value of 0.0027 suggested a statistically significant
nonzero difference, with a mean value of -0.153 (SE 0.038). Three studies,
including GeparSixto, BOOG, and Neo-tAnGo, were used for validation. The F test
suggested the model fit the test data well. IMPLICATIONS: The observed hazard
ratios fit well with the predicted hazard ratios for both EFS and OS and suggest
plausible trial-level associations with the new predictor. MAJOR FINDINGS: Our
model predicted the correlation between pCR and EFS as well as OS. This model
could be used as a supporting tool to help interpret positive pCR results in
neoadjuvant clinical studies in patients with high-risk EBC.
PMID- 29959105
TI - Phase-III, randomized controlled trial of the behavioral intervention for
increasing physical activity in multiple sclerosis: Project BIPAMS.
AB - BACKGROUND: We propose a phase-III, randomized controlled trial (RCT) that
examines the effectiveness of a behavioral intervention based on social cognitive
theory (SCT) and delivered through the Internet using e-learning approaches for
increasing physical activity and secondary outcomes (e.g., symptoms) in a large
sample of people with multiple sclerosis (MS) residing throughout the United
States. METHODS/DESIGN: The proposed phase-III trial will use a parallel group,
RCT design that examines the effect of a 6-month behavioral intervention for
increasing physical activity and secondarily improving mobility, cognition,
symptoms, and quality of life (QOL) in persons with MS. The primary outcome is
accelerometer-measured moderate-to-vigorous physical activity (MVPA). The
secondary outcomes include self-report measures of physical activity, walking
impairment, cognition, fatigue, depression, anxiety, pain, sleep quality, and
QOL. The tertiary outcomes are mediator variables based on SCT. Participants (N =
280) will be randomized into behavioral intervention (n = 140) or attention and
social contact control (n = 140) conditions using computerized random numbers
with concealed allocation. The conditions will be administered over 6-months by
persons who are uninvolved in screening, recruitment, random assignment, and
outcome assessment. There will be a 6-month follow-up without intervention
access/content. We will collect primary, secondary, and tertiary outcome data
every 6 months over the 12-month period. Data analysis will involve intent-to
treat principles and latent growth modeling (LGM). DISCUSSION: The proposed
research will provide evidence for the effectiveness of a novel, widely scalable
approach for increasing lifestyle physical activity and improving secondary
outcomes and QOL in persons with MS.
PMID- 29959106
TI - #Healthy Selfies: Exploration of Health Topics on Instagram.
AB - BACKGROUND: Social media provides a complementary source of information for
public health surveillance. The dominate data source for this type of monitoring
is the microblogging platform Twitter, which is convenient due to the free
availability of public data. Less is known about the utility of other social
media platforms, despite their popularity. OBJECTIVE: This work aims to
characterize the health topics that are prominently discussed in the image
sharing platform Instagram, as a step toward understanding how this data might be
used for public health research. METHODS: The study uses a topic modeling
approach to discover topics in a dataset of 96,426 Instagram posts containing
hashtags related to health. We use a polylingual topic model, initially developed
for datasets in different natural languages, to model different modalities of
data: hashtags, caption words, and image tags automatically extracted using a
computer vision tool. RESULTS: We identified 47 health-related topics in the data
(kappa=.77), covering ten broad categories: acute illness, alternative medicine,
chronic illness and pain, diet, exercise, health care & medicine, mental health,
musculoskeletal health and dermatology, sleep, and substance use. The most
prevalent topics were related to diet (8,293/96,426; 8.6% of posts) and exercise
(7,328/96,426; 7.6% of posts). CONCLUSIONS: A large and diverse set of health
topics are discussed in Instagram. The extracted image tags were generally too
coarse and noisy to be used for identifying posts but were in some cases accurate
for identifying images relevant to studying diet and substance use. Instagram
shows potential as a source of public health information, though limitations in
data collection and metadata availability may limit its use in comparison to
platforms like Twitter.
PMID- 29959107
TI - Learnability of a Configurator Empowering End Users to Create Mobile Data
Collection Instruments: Usability Study.
AB - BACKGROUND: Many research domains still heavily rely on paper-based data
collection procedures, despite numerous associated drawbacks. The QuestionSys
framework is intended to empower researchers as well as clinicians without
programming skills to develop their own smart mobile apps in order to collect
data for their specific scenarios. OBJECTIVE: In order to validate the
feasibility of this model-driven, end-user programming approach, we conducted a
study with 80 participants. METHODS: Across 2 sessions (7 days between Session 1
and Session 2), participants had to model 10 data collection instruments (5 at
each session) with the developed configurator component of the framework. In this
context, performance measures like the time and operations needed as well as the
resulting errors were evaluated. Participants were separated into two groups (ie,
novices vs experts) based on prior knowledge in process modeling, which is one
fundamental pillar of the QuestionSys framework. RESULTS: Statistical analysis (t
tests) revealed that novices showed significant learning effects for errors
(P=.04), operations (P<.001), and time (P<.001) from the first to the last use of
the configurator. Experts showed significant learning effects for operations
(P=.001) and time (P<.001), but not for errors as the experts' errors were
already very low at the first modeling of the data collection instrument.
Moreover, regarding the time and operations needed, novices got significantly
better at the third modeling task than experts were at the first one (t tests;
P<.001 for time and P=.002 for operations). Regarding errors, novices did not get
significantly better at working with any of the 10 data collection instruments
than experts were at the first modeling task, but novices' error rates for all 5
data collection instruments at Session 2 were not significantly different anymore
from those of experts at the first modeling task. After 7 days of not using the
configurator (from Session 1 to Session 2), the experts' learning effect at the
end of Session 1 remained stable at the beginning of Session 2, but the novices'
learning effect at the end of Session 1 showed a significant decay at the
beginning of Session 2 regarding time and operations (t tests; P<.001 for time
and P=.03 for operations). CONCLUSIONS: In conclusion, novices were able to use
the configurator properly and showed fast (but unstable) learning effects,
resulting in their performances becoming as good as those of experts (which were
already good) after having little experience with the configurator. Following
this, researchers and clinicians can use the QuestionSys configurator to develop
data collection apps for smart mobile devices on their own.
PMID- 29959108
TI - Connecting With Your Dentist on Facebook: Patients' and Dentists' Attitudes
Towards Social Media Usage in Dentistry.
AB - BACKGROUND: Social media has begun to proliferate across medical areas and
transformed how medical professionals serve and interact with their patients. It
offers a new communication avenue that has the potential to engage patients and,
hence, may be used to create value for both medical professionals and patients.
In dentistry, even though patients and dentists frequently use social media in
their personal lives, little is known about their attitudes and expectations
toward using social media for professional interactions. OBJECTIVE: In this
paper, we focus on the role of social media in dentistry. Specifically, we
explore patients' and dentists' attitudes toward social media usage and their
current online behaviors in this context. Furthermore, we examine potential
challenges and opportunities regarding dentists' adoption of social media
practices. METHODS: This research employed a large-scale online survey of 588
patients and 532 dental professionals. We assessed the attitudes, expectations,
and social media behaviors from both patients' and dentists' perspectives.
RESULTS: We found that more than 55% (290/532) of dentists in our sample have
accounts for their dental practice on various social media platforms.
Interestingly, while 73% (374/511) of patients did not expect their dental
practice to have a social media presence, and 44% (207/468) thought that
establishing a friendship with their dentists is not appropriate, the findings
show that 36% (164/460) of patients had searched for their dentists, and 44%
(207/470) of them were happy to establish contacts with dentists on social media.
Furthermore, the findings highlight that patients were interested in exploring
additional information such as online reviews and the qualifications of their
dentists on Facebook pages. For dentists, more than half (375/432, 83%) of them
in our sample thought that social media marketing is more efficient compared to
traditional marketing. CONCLUSIONS: Our findings revealed some key challenges and
opportunities to utilize social media in dentistry. For both patients and
dentists, the role of social media in dental services remains vague, and both
parties still share concerns about connecting with each other on social media
platforms. However, there also exists a sizeable number of patients who are
already comfortable to connect with their dentists on social media sites such as
Facebook. The current findings show that there is an opportunity for dental
practices to trade upon a more active social media presence for enhanced patient
interaction and engagement.
PMID- 29959109
TI - Self-Management of Chronic Diseases Among Older Korean Adults: An mHealth
Training, Protocol, and Feasibility Study.
AB - BACKGROUND: Most training programs for self-management of chronic diseases in
Korea currently involve face-to-face interactions primarily in a health care
setting. Therefore, older Koreans living in the community continue to seek other
training opportunities for the management of chronic diseases. This has led to
the development of new training methods, such as mobile health (mHealth) care,
which are valuable in community centers and homes. OBJECTIVE: This feasibility
study (1) developed an mHealth training protocol to empower community-dwelling
elderly individuals to manage their chronic diseases; (2) examined the
feasibility of delivering this mHealth training protocol to elderly individuals
through mobile tablets and applications (apps); and (3) discussed the contextual
and methodological challenges associated with the development of this protocol.
METHODS: The mHealth training protocol was developed based on the eHealth
Enhanced Chronic Care Model and comprised of four phases. Phase 1 included
standardized technology (mobile tablets) training using guidebooks,
demonstrations, and guided practice. Phase 2 included provision of standardized
information about disease management that was obtained from governmental and
professional health care organizations. Phase 3 included provision of training on
the use of high-quality mHealth apps that were selected based on individual
diagnoses. Phase 4 included encouraging the patients to practice using self
selected mHealth apps based on their individual needs. Quantitative descriptive
statistics and qualitative content analyses of user evaluations were used to
assess the feasibility and user acceptance of this protocol. RESULTS: Of the 27
older adults included in this study, 25 completed all 4 weeks of the mHealth
training. The attrition rate was 7% (2/27), and the reasons included time
conflicts, emotional distress, and/or family discouragement. The men required
little or no training for Phase 1, and in comparison with men, women seemed to
depend more on the mHealth trainers in Phase 3. Gender, level of education, and
previous experience of using smartphones were associated with the speed of
learning, level of confidence, and overall competence. CONCLUSIONS: A tailored
and personalized approach is required to develop mHealth training protocols for
older adults. Self-management of chronic diseases via mHealth training requires
careful consideration of the complex nature of human behavior, emotional
responses, and familial influences. Therefore, integration of a theoretical,
clinical, and technical approach is necessary for the successful development and
implementation of an mHealth training program that targets older adults with
chronic diseases in a community setting.
PMID- 29959110
TI - Augmenting Qualitative Text Analysis with Natural Language Processing:
Methodological Study.
AB - BACKGROUND: Qualitative research methods are increasingly being used across
disciplines because of their ability to help investigators understand the
perspectives of participants in their own words. However, qualitative analysis is
a laborious and resource-intensive process. To achieve depth, researchers are
limited to smaller sample sizes when analyzing text data. One potential method to
address this concern is natural language processing (NLP). Qualitative text
analysis involves researchers reading data, assigning code labels, and
iteratively developing findings; NLP has the potential to automate part of this
process. Unfortunately, little methodological research has been done to compare
automatic coding using NLP techniques and qualitative coding, which is critical
to establish the viability of NLP as a useful, rigorous analysis procedure.
OBJECTIVE: The purpose of this study was to compare the utility of a traditional
qualitative text analysis, an NLP analysis, and an augmented approach that
combines qualitative and NLP methods. METHODS: We conducted a 2-arm cross-over
experiment to compare qualitative and NLP approaches to analyze data generated
through 2 text (short message service) message survey questions, one about
prescription drugs and the other about police interactions, sent to youth aged 14
24 years. We randomly assigned a question to each of the 2 experienced
qualitative analysis teams for independent coding and analysis before receiving
NLP results. A third team separately conducted NLP analysis of the same 2
questions. We examined the results of our analyses to compare (1) the similarity
of findings derived, (2) the quality of inferences generated, and (3) the time
spent in analysis. RESULTS: The qualitative-only analysis for the drug question
(n=58) yielded 4 major findings, whereas the NLP analysis yielded 3 findings that
missed contextual elements. The qualitative and NLP-augmented analysis was the
most comprehensive. For the police question (n=68), the qualitative-only analysis
yielded 4 primary findings and the NLP-only analysis yielded 4 slightly different
findings. Again, the augmented qualitative and NLP analysis was the most
comprehensive and produced the highest quality inferences, increasing our depth
of understanding (ie, details and frequencies). In terms of time, the NLP-only
approach was quicker than the qualitative-only approach for the drug (120 vs 270
minutes) and police (40 vs 270 minutes) questions. An approach beginning with
qualitative analysis followed by qualitative- or NLP-augmented analysis took
longer time than that beginning with NLP for both drug (450 vs 240 minutes) and
police (390 vs 220 minutes) questions. CONCLUSIONS: NLP provides both a
foundation to code qualitatively more quickly and a method to validate
qualitative findings. NLP methods were able to identify major themes found with
traditional qualitative analysis but were not useful in identifying nuances.
Traditional qualitative text analysis added important details and context.
PMID- 29959111
TI - Web-Based Intervention for Family Carers of Persons with Dementia and Multiple
Chronic Conditions (My Tools 4 Care): Pragmatic Randomized Controlled Trial.
AB - BACKGROUND: My Tools 4 Care (MT4C) is a Web-based intervention that was developed
based on the transitions theory. It is an interactive, self-administered, and
portable toolkit containing six main sections intended to support carers of
community-living persons with Alzheimer's disease and related dementia and
multiple chronic conditions through their transition experiences. OBJECTIVE: The
objective of our study was to evaluate the effectiveness of MT4C with respect to
increasing hope, self-efficacy, and health-related quality of life in carers of
community-living older persons with Alzheimer's disease and related dementia and
multiple chronic conditions. METHODS: A multisite, pragmatic, mixed methods,
longitudinal, repeated-measures, randomized controlled trial was conducted
between June 2015 and April 2017. Eligible participants were randomized into
either treatment (MT4C) or educational control groups. Following baseline
measures, carers in the treatment group received 3 months of password-protected
access to MT4C. Trained research assistants collected data from participants via
phone on hope (Herth Hope Index [HHI]), self-efficacy (General Self-Efficacy
Scale), and health-related quality of life (Short Form-12 item [version 2] health
survey; SF-12v2) at baseline, 1, 3, and 6 months. The use and cost of health and
social services (Health and Social Services Utilization Inventory) among
participants were measured at baseline, 3, and 6 months. Analysis of covariance
was used to identify group differences at 3 months, and generalized estimating
equations were used to identify group differences over time. RESULTS: A total of
199 carers participated in this study, with 101 participants in the treatment
group and 98 in the educational control group. Of all, 23% (45/199) participants
withdrew during the study for various reasons, including institutionalization or
death of the person with dementia and lack of time from the carer. In the
treatment group, 73% (74/101) carers used MT4C at least once over the 3-month
period. No significant differences in the primary outcome measure (mental
component summary score from the SF-12v2) by group or time were noted at 3
months; however, significant differences were evident for HHI-factor 2 (P=.01),
with higher hope scores in the treatment group than in the control group. General
estimating equations showed no statistically significant group differences in
terms of mental component summary score at all time points. Attrition and the
fact that not all carers in the treatment group used MT4C may explain the absence
of statistically significant results for the main outcome variable. CONCLUSIONS:
Despite no significant differences between groups in terms of the primary outcome
variable (mental component score), the significant differences in terms of one of
the hope factors suggest that MT4C had a positive influence on the lives of
participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT02428387;
https://clinicaltrials.gov/ct2/show/NCT02428387 (Archived by Webcite at
http://www.webcitation.org/708oFCR8h).
PMID- 29959112
TI - Development of an Agent-Based Model to Investigate the Impact of HIV Self-Testing
Programs on Men Who Have Sex With Men in Atlanta and Seattle.
AB - BACKGROUND: In the United States HIV epidemic, men who have sex with men (MSM)
remain the most profoundly affected group. Prevention science is increasingly
being organized around HIV testing as a launch point into an HIV prevention
continuum for MSM who are not living with HIV and into an HIV care continuum for
MSM who are living with HIV. An increasing HIV testing frequency among MSM might
decrease future HIV infections by linking men who are living with HIV to
antiretroviral care, resulting in viral suppression. Distributing HIV self-test
(HIVST) kits is a strategy aimed at increasing HIV testing. Our previous modeling
work suggests that the impact of HIV self-tests on transmission dynamics will
depend not only on the frequency of tests and testers' behaviors but also on the
epidemiological and testing characteristics of the population. OBJECTIVE: The
objective of our study was to develop an agent-based model to inform public
health strategies for promoting safe and effective HIV self-tests to decrease the
HIV incidence among MSM in Atlanta, GA, and Seattle, WA, cities representing
profoundly different epidemiological settings. METHODS: We adapted and extended a
network- and agent-based stochastic simulation model of HIV transmission dynamics
that was developed and parameterized to investigate racial disparities in HIV
prevalence among MSM in Atlanta. The extension comprised several activities:
adding a new set of model parameters for Seattle MSM; adding new parameters for
tester types (ie, regular, risk-based, opportunistic-only, or never testers);
adding parameters for simplified pre-exposure prophylaxis uptake following
negative results for HIV tests; and developing a conceptual framework for the
ways in which the provision of HIV self-tests might change testing behaviors. We
derived city-specific parameters from previous cohort and cross-sectional studies
on MSM in Atlanta and Seattle. Each simulated population comprised 10,000 MSM and
targeted HIV prevalences are equivalent to 28% and 11% in Atlanta and Seattle,
respectively. RESULTS: Previous studies provided sufficient data to estimate the
model parameters representing nuanced HIV testing patterns and HIV self-test
distribution. We calibrated the models to simulate the epidemics representing
Atlanta and Seattle, including matching the expected stable HIV prevalence. The
revised model facilitated the estimation of changes in 10-year HIV incidence
based on counterfactual scenarios of HIV self-test distribution strategies and
their impact on testing behaviors. CONCLUSIONS: We demonstrated that the
extension of an existing agent-based HIV transmission model was sufficient to
simulate the HIV epidemics among MSM in Atlanta and Seattle, to accommodate a
more nuanced depiction of HIV testing behaviors than previous models, and to
serve as a platform to investigate how HIV self-tests might impact testing and
HIV transmission patterns among MSM in Atlanta and Seattle. In our future
studies, we will use the model to test how different HIV self-test distribution
strategies might affect HIV incidence among MSM.
PMID- 29959114
TI - Deception and Shopping Behavior Among Current Cigarette Smokers: A Web-Based,
Randomized Virtual Shopping Experiment.
AB - BACKGROUND: Virtual stores can be used to identify influences on consumer
shopping behavior. Deception is one technique that may be used to attempt to
increase the realism of virtual stores. OBJECTIVE: The objective of the
experiment was to test whether the purchasing behavior of participants in a
virtual shopping task varied based on whether they were told that they would
receive the products they selected in a virtual convenience store (a form of
deception) or not. METHODS: We recruited a US national sample of 402 adult
current smokers by email from an online panel of survey participants. They
completed a fully automated randomized virtual shopping experiment with a US $15
or US $20 budget in a Web-based virtual convenience store. We told a random half
of participants that they would receive the products they chose in the virtual
store or the cash equivalent (intervention condition), and the other random half
simply to conduct a shopping task (control condition). We tested for differences
in demographics, tobacco use behaviors, and in-store purchases (outcome variable,
assessed by questionnaire) by experimental condition. RESULTS: The
characteristics of the participants (398/402, 99.0% with complete data) were
comparable across conditions except that the intervention group contained
slightly more female participants (103/197, 52.3%) than the control group
(84/201, 41.8%; P=.04). We did not find any other significant differences in any
other demographic variables or tobacco use, or in virtual store shopping
behaviors, including purchasing any tobacco (P=.44); purchasing cigarettes
(P=.16), e-cigarettes (P=.54), cigars (P=.98), or smokeless tobacco (P=.72);
amount spent overall (P=.63) or on tobacco (P=.66); percentage of budget spent
overall (P=.84) or on tobacco (P=.74); number of total items (P=.64) and tobacco
items purchased (P=.54); or total time spent in the store (P=.07). CONCLUSIONS:
We found that telling participants that they will receive the products they
select in a virtual store did not influence their purchases. This finding
suggests that deception may not affect consumer behavior and, as a result, may
not be necessary in virtual shopping experiments.
PMID- 29959113
TI - Misleading Claims About Tobacco Products in YouTube Videos: Experimental Effects
of Misinformation on Unhealthy Attitudes.
AB - BACKGROUND: Recent content analyses of YouTube postings reveal a proliferation of
user generated videos with misleading statements about the health consequences of
various types of nontraditional tobacco use (eg, electronic cigarettes; e
cigarettes). OBJECTIVE: This research was aimed at obtaining evidence about the
potential effects of YouTube postings about tobacco products on viewers'
attitudes toward these products. METHODS: A sample of young adults recruited
online (N=350) viewed one of four highly viewed YouTube videos containing
misleading health statements about chewing tobacco, e-cigarettes, hookahs, and
pipe smoking, as well as a control YouTube video unrelated to tobacco products.
RESULTS: The videos about e-cigarettes and hookahs led to more positive attitudes
toward the featured products than did control videos. However, these effects did
not fully translate into attitudes toward combustive cigarette smoking, although
the pipe video led to more positive attitudes toward combustive smoking than did
the chewing and the hookah videos, and the e-cigarette video led to more positive
attitudes toward combustive cigarette smoking than did the chewing video.
CONCLUSIONS: This research revealed young people's reactions to misleading claims
about tobacco products featured in popular YouTube videos. Policy implications
are discussed.
PMID- 29959115
TI - Therapeutic Management of Dyslipidemia Patients at Very High Cardiovascular Risk
(CARDIO TRACK): Protocol for the Observational Registry Study.
AB - BACKGROUND: Dyslipidemia is a major modifiable risk factor for atherosclerotic
cardiovascular disease. Current South African guidelines recommend titrating
lipid-lowering therapy (LLT) to low-density lipoprotein cholesterol (LDL-C)
targets stratified by cardiovascular risk. The LDL-C goal for very high-risk
patients is <1.8 mmol/L. In international studies, approximately 30% of patients
do not achieve this goal despite receiving maximally tolerated statin doses.
There is, however, a paucity of data on LDL-C goal achievement in very high-risk
South African patients receiving maximal statin doses. OBJECTIVE: The goal of the
research it to assess LDL-C goal achievement in, and clinical characteristics of,
very high cardiovascular risk dyslipidemic patients receiving maximal tolerated
statin doses with or without ezetimibe. METHODS: This is an observational, cross
sectional South African registry study that plans to include up to 30 sites and
500 study participants. Adult patients with very high cardiovascular risk status
receiving stable, maximally tolerated statin doses (with or without ezetimibe)
will be eligible for inclusion. RESULTS: Funding has been awarded and enrollment
began on November 15, 2017, and was completed on April 13, 2018, with 507
participants. Database lock was done on June 21, 2018. The statistical analysis
has commenced and we expect the final clinical study report to be completed by
October 2018. CONCLUSIONS: This study will document the adequacy of LLT in those
at highest risk and will thus fill an important data gap in South Africa. This
data may be useful in assessing the need for novel LLTs like proprotein
convertase subtilisin/kexin 9 inhibitors that substantially lower cholesterol
levels in addition to optimal statin therapy. REGISTERED REPORT IDENTIFIER: RR1
10.2196/9248.
PMID- 29959116
TI - [Regulation of gamma-globin gene expression and its clinical applications].
AB - Human hemoglobin, a tetramer containing two alpha globins and two beta globins,
is responsible for oxygen transportation in the body. Globin genes are clustered
in the genome and their expressions are regulated by a variety of cis-acting
elements and trans-acting factors, exhibiting a developmental- and tissue
specific manner. beta-thalassemia and sickle cell diseases are two of the most
common autosomal recessive disorders caused by mutations in the beta-globin gene.
Besides alpha- and beta-globins, the human genome also has a third globin gene
gamma-globin. Like beta-globin, gamma-globin also has oxygen-carrying
capabilities. Unlike beta-globin, gamma-globin is mainly expressed at the fetal
stage and remains intact in beta-thalassemia and sickle cell disease patients.
Thus, reactivating the expression of the gamma-globin gene in adult patients to
ameliorate their clinical symptoms has become one of the best therapeutic
strategies to treat beta-thalassemia and sickle cell diseases. Some drugs have
been developed clinically to increase gamma-globin gene expression for those
patients. With the development of genome editing technologies, precision gene
therapy for these diseases is underway. This review focuses on the main
transcription factors and epigenetic modifiers that are involved in gamma-globin
gene regulation, and some applications for clinical treatment for beta
thalassemia and sickle cell diseases based on these studies. We hope to provide a
useful reference for in-depth studies on transcriptional regulation of gamma
globin gene expression in the future.
PMID- 29959117
TI - [Molecular mechanisms of genetic transposition inhibition by piRNA].
AB - Transposable elements (TEs) are DNA elements that can change their position
within or between chromosomes. Most active TEs are retrotransposons, which
transpose through a RNA intermediate. Since retrotransposons comprise high
proportions in cell genomes, their frequent transposition may cause deleterious
effects on the structure and function of the host cell genomes, thus causing
serious genetic diseases such as cancer. Host cells therefore developed defense
strategies to restrict these mobile elements. piRNA, which belongs to non-coding
interfering RNAs, can efficiently decrease the level of retrotransposon RNA
intermediates at transcriptional or post-transcriptional stages. In this review,
we summarize the progress in mechanisms of piRNA-mediated retrotransposon
inhibition. We hope that this review may shed light on the research of transposon
and genome regulation.
PMID- 29959118
TI - [Progress in innate immunity-related genes in insects].
AB - Insects have evolved a strong innate immune system to defense pathogens and
adverse conditions. Insect innate immune system comprises of humoral immunity and
cellular immunity. Humoral immunity mainly includes three signaling pathways,
i.e., Toll, IMD and JAK/STAT, by which signal transduction and immune pathways
regulate expression of immune-related genes and activate antimicrobial peptides
and other effectors. Cellular immunity contains phagocytosis, encapsulation and
nodulation of pathogens, which is mediated by hemolymph cells. In recent years,
with the rapid development of insect genomics, a large number of immune-related
genes have been characterized from insect genome data using bioinformatic
methods. Studies on these genes have significantly deepened the understanding of
molecular mechanisms of insect innate immune system. Insect immune-related genes
can be divided into seven categories by gene functions: recognition, signaling
transduction, modulator, effectors, melanization, RNA interference and other
genes. The humoral immunity and cellular immunity are regulated by the
interactions among these immune-related genes. In this review, we summarize the
classification, function and evolution of insect immune-related genes, and
propose future research directions of insect innate immunity, which will be
helpful for understanding molecular mechanisms of insect innate immune system and
developing new strategies for controlling pest insects.
PMID- 29959119
TI - [Progress in circular RNAs of plants].
AB - Circular RNAs (circRNAs) are covalently closed, conserved single-stranded
transcripts that are produced from precursor mRNA (pre-mRNA) back-splicing. They
could function as microRNA sponges, interfere with splicing and bind to protein
to regulate the expression of parental genes and linear mRNAs. Next-generation
RNA sequencing (RNA-seq) has recently shown that the expression of circRNAs is
widespread in plants. circRNAs participate in multiple biological processes such
as floral development, fruit ripening, and biotic and abiotic stress responses by
cell type-specific and tissue-specific expression patterns, indicating that they
may play an important role in plant development. In this review, we summarize the
current knowledge of plant circRNAs in recent years, including the biogenesis,
detection, databases, expression pattern, and potential functions in comparison
with animal results to provide new insights for functional research interests of
circRNAs in the future.
PMID- 29959120
TI - [Mutant generation of the testis genes and phenotype analyses in Drosophila].
AB - Multiple genes work together to maintain the normal functions of the reproductive
system. However, for many of these genes, little is known about their specific
functions and mechanisms. In the present study, eight Drosophila genes, including
CG4161, CG11475, CG2921, CG10541, CG7276, CG3800, CG8117 and CG16779, were
selected for detailed studies based on their testis expression, undefined
functions, and having highly homologous and conserved genes in humans (Homo
sapiens) and mouse (Mus musculus). We analyzed their expression levels in
different tissues, and determined their probably functions in male reproduction.
The results showed that the first five genes were mainly expressed in testis,
while other three showed ubiquitous expression in all tissues examined. Using the
CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR
associated protein 9) and homology-directed repair (HDR) strategies, we have
systematically generated the mutants of these genes and studied their functions
in male reproduction. Loss of function of CG7276 and CG3800 resulted in partial
sterility and reduction of the offspring number, while other genes showed no
significant impact on fertility. CG7276 -/- and CG3800 -/- mutants were partial
sterile and showed various types of abnormities, including seminal vesicle
atrophy, spermatogonial stem cell reduction and cellular distribution disorders.
Results of DNA and F-actin staining also indicated that CG7276 and CG3800 could
play important roles in spermiogenesis. The establishments of these mutants have
provided means to unravel the functions and mechanisms of these genes in animal
models.
PMID- 29959121
TI - [Comparative analysis on the transcriptomes of the prostates of muskrats at
breeding stage and non-breeding stage].
AB - The muskrat (Ondatra zibethicus L.) is a seasonal breeding animal. Adult male
muskrat has a pair of scent glands between the muscle and skin above the
urogenital tract, which secrete muskrat musk during the breeding stage. Compared
with other rodents, the muskrat prostates and seminal vesicles are very well
developed throughout the breeding stage. Studies have shown that intraperitoneal
injection of muskrat musk can readily promote the development of the prostates
and seminal vesicles in the male mice, suggesting a tight correlation between
musk secretion and the development of the prostates and seminal vesicles in the
muskrat. In this study, RNA-seq technology was used to analyze the gene
expression patterns were further investigated by gene ontology (GO) analysis and
KEGG pathway analysis. The results showed that 1629 genes were significantly and
differentially expressed and were involved in a variety of signal transductions
and energy metabolism pathways. The differential expression patterns of the OBP2
gene, and members of the Bcl-2 family and tumor necrosis factor receptor
superfamily suggest that the prostate development in muskrat is controlled by a
variety of molecular mechanisms; and the musk secreted by the muskrat scent
glands might participate in the regulation of such developmental processes.
PMID- 29959122
TI - [Preliminary analysis of the role of GmSnRK1.1 and GmSnRK1.2 in the ABA and
alkaline stress response of the soybean using the CRISPR/Cas9-based gene double
knockout system].
AB - Sucrose non-fermenting related protein kinases (SnRKs) are a ubiquitous Ser/Thr
protein kinase in the plant kingdom. These kinases play important roles in plant
growth, development, metabolism and resistance to environmental stresses. The
soybean (Glycine max L.) genome has four SnRK1 genes, of which GmSnRK1.1 and
GmSnRK1.2 are predominant and participate in multiple stress response pathways.
To dissect the mechanism of the role of GmSnRK1.1 and GmSnRK1.2 proteins in
response to ABA and alkaline stresses, we constructed a dual-gRNA CRISPR vector
to specifically knock out GmSnRK1.1 and GmSnRK1.2. The resultant constructs were
transformed into soybean cotyledon nodes to induce hairy roots by agrobacteria
(Agrobacterium rhizogenes). The soybean hairy roots obtained were genotyped, and
the results showed that GmSnRK1.1 and GmSnRK1.2 were efficiently doubly knocked
out in 48.6% hairy roots. We also generated control hairy roots that over
expressed GmSnRK1. The materials were treated with 25 MUmol/L ABA for 15 days and
the results showed that the growths of wild-type and GmSnRK1 over-expressed roots
were significantly inhibited than GmSnRK1.1 GmSnRK1.2 double-knockout roots, as
the controls displayed less root lengths and fresh weights. However, after
treating with 50 mmol/L NaHCO3 for 15 days, we found that the growths of
GmSnRK1.1 GmSnRK1.2 double-knockout roots were significantly inhibited than the
wild-type and GmSnRK1 over-expressed control roots, as the knockout groups
contained less root lengths and fresh weights. These results implied that the
GmSnRK1.1 GmSnRK1.2 double knockout mitigated hairy root sensitivity to ABA and
resistance to alkaline stress. Taken together, we established the CRISPR/Cas9
system to perform gene double knockout in the soybean and by using this
technique, we determined the roles of GmSnRK1.1 and GmSnRK1.2 in response of
abiotic stresses.
PMID- 29959123
TI - [Recommendations to define generation and apply generation symbols in plant
genetics].
AB - Genetics is the science of studying the inheritance and variation of organisms.
It is one of the biological disciplines that explore the rules of the structure,
function, variation and transmission of genes. The concept and category of
generation in plant genetics is a simple issue, but the usage of generation
symbols is arbitrary so far. Different symbols are often used to express the same
type of hybrid offspring, such as the traditional hybrid expressed in F1 or F0,
and the regenerated plants in the tissue culture are expressed in R or R0 or R1,
which leads to the fuzzy basic concepts of genetics. According to new generations
generated by different methods and their genetic composition, the paper puts
forward some suggestions to apply symbols to the new generation, so as to
facilitate the study and research of plant genetics.
PMID- 29959124
TI - Latest legal challenge to tobacco plain packaging is rejected by the World Trade
Organization.
PMID- 29959125
TI - Consultant obstetrician and gynaecologist is struck off for groping four female
colleagues.
PMID- 29959126
TI - BMA is urged to back doctors who refuse to take part in government's Prevent
programme.
PMID- 29959127
TI - Limping in children: look what the cat dragged in!
PMID- 29959128
TI - Is obesity associated with depression in children? Systematic review and meta
analysis.
AB - OBJECTIVES: To compare the odds of depression in obese and overweight children
with that in normal-weight children in the community. DESIGN: Systematic review
and random-effect meta-analysis of observational studies. DATA SOURCES: EMBASE,
PubMed and PsychINFO electronic databases, published between January 2000 and
January 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Cross-sectional or
longitudinal observational studies that recruited children (aged <18 years) drawn
from the community who had their weight status classified by body mass index,
using age-adjusted and sex-adjusted reference charts or the International Obesity
Task Force age-sex specific cut-offs, and concurrent or prospective odds of
depression were measured. RESULTS: Twenty-two studies representing 143 603
children were included in the meta-analysis. Prevalence of depression among obese
children was 10.4%. Compared with normal-weight children, odds of depression were
1.32 higher (95% CI 1.17 to 1.50) in obese children. Among obese female children,
odds of depression were 1.44 (95% CI 1.20 to 1.72) higher compared with that of
normal-weight female children. No association was found between overweight
children and depression (OR 1.04, 95% CI 0.95 to 1.14) or among obese or
overweight male subgroups and depression (OR 1.14, 95% CI 0.93 to 1.41% and 1.08,
95% CI 0.85 to 1.37, respectively). Subgroup analysis of cross-sectional and
longitudinal studies separately revealed childhood obesity was associated with
both concurrent (OR 1.26, 95% CI 1.09 to 1.45) and prospective odds (OR 1.51, 95%
CI 1.21 to 1.88) of depression. CONCLUSION: We found strong evidence that obese
female children have a significantly higher odds of depression compared with
normal-weight female children, and this risk persists into adulthood. Clinicians
should consider screening obese female children for symptoms of depression.
BACKGROUND: Childhood mental illness is poorly recognised by healthcare providers
and parents, despite half of all lifetime cases of diagnosable mental illness
beginning by the age of 14 years.1 Globally, depression is the leading cause of
disease burden, as measured by disability-adjusted life years, in children aged
10-19 years.2 Untreated, it is associated with poor school performance and social
functioning, substance misuse, recurring depression in adulthood and increased
suicide risk, which is the second leading cause of preventable death among young
people.3-6 The resulting cost to the National Health Service of treating
depression is estimated at over L2 billion, and the wider social and economic
impact of depression is likely to be considerable.7.
PMID- 29959130
TI - System pressures should be considered in gross negligence manslaughter cases,
says BMA.
PMID- 29959131
TI - High Throughput Sequencing and Assessing Disease Risk.
AB - High-throughput sequencing has dramatically improved our ability to determine and
diagnose the underlying causes of human disease. The use of whole-genome and
whole-exome sequencing has facilitated faster and more cost-effective
identification of new genes implicated in Mendelian disease. It has also improved
our ability to identify disease-causing mutations for Mendelian diseases whose
associated genes are already known. These benefits apply not only in cases in
which the objective is to assess genetic disease risk in adults and children, but
also for prenatal genetic testing and embryonic testing. High-throughput
sequencing has also impacted our ability to assess risk for complex diseases and
will likely continue to influence this area of disease research as more and more
individuals undergo sequencing and we better understand the significance of
variation, both rare and common, across the genome. Through these activities,
high-throughput sequencing has the potential to revolutionize medicine.
PMID- 29959132
TI - Prostate Cancer Epigenetics: From Basic Mechanisms to Clinical Implications.
AB - A level of epigenetic programming, encoded by complex sets of chemical marks on
DNA and histones, and by context-specific DNA, RNA, protein interactions, that
all regulate the structure, organization, and function of the genome, is critical
to establish both normal and neoplastic cell identities and functions. This
structure-function relationship of the genome encoded by the epigenetic
programming can be thought of as an epigenetic cityscape that is built on the
underlying genetic landscape. Alterations in the epigenetic cityscape of prostate
cancer cells compared with normal prostate tissues have a complex interplay with
genetic alterations to drive prostate cancer initiation and progression. Indeed,
mutations in genes encoding epigenetic enzymes are often observed in human
cancers including prostate cancer. Interestingly, alterations in the prostate
cancer epigenetic cityscape can be highly recurrent, a facet that can be
exploited for development of biomarkers and potentially as therapeutic targets.
PMID- 29959129
TI - Inhibition of Epidermal Growth Factor Receptor Activation Is Associated With
Improved Diabetic Nephropathy and Insulin Resistance in Type 2 Diabetes.
AB - Previous studies by us and others have indicated that renal epidermal growth
factor receptors (EGFR) are activated in models of diabetic nephropathy (DN) and
that inhibition of EGFR activity protects against progressive DN in type 1
diabetes. In this study we examined whether inhibition of EGFR activation would
affect the development of DN in a mouse model of accelerated type 2 diabetes (BKS
db/db with endothelial nitric oxide knockout [eNOS-/-db/db]). eNOS-/-db/db mice
received vehicle or erlotinib, an inhibitor of EGFR tyrosine kinase activity,
beginning at 8 weeks of age and were sacrificed at 20 weeks of age. In addition,
genetic models inhibiting EGFR activity (waved 2) and transforming growth factor
alpha (waved 1) were studied in this model of DN in type 2 diabetes. Compared
with vehicle-treated mice, erlotinib-treated animals had less albuminuria and
glomerulosclerosis, less podocyte loss, and smaller amounts of renal profibrotic
and fibrotic components. Erlotinib treatment decreased renal oxidative stress,
macrophage and T-lymphocyte infiltration, and the production of proinflammatory
cytokines. Erlotinib treatment also preserved pancreas function, and these mice
had higher blood insulin levels at 20 weeks, decreased basal blood glucose
levels, increased glucose tolerance and insulin sensitivity, and increased blood
levels of adiponectin compared with vehicle-treated mice. Similar to the
aforementioned results, both waved 1 and waved 2 diabetic mice also had
attenuated DN, preserved pancreas function, and decreased basal blood glucose
levels. In this mouse model of accelerated DN, inhibition of EGFR signaling led
to increased longevity.
PMID- 29959133
TI - Considerations from the Innovation and Quality Induction Working Group in
Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on
CYP3A4 mRNA In Vitro Response Thresholds, Variability, and Clinical Relevance.
AB - The Innovation and Quality Induction Working Group presents an assessment of best
practice for data interpretation of in vitro induction, specifically, response
thresholds, variability, application of controls, and translation to clinical
risk assessment with focus on CYP3A4 mRNA. Single concentration control data and
Emax/EC50 data for prototypical CYP3A4 inducers were compiled from many human
hepatocyte donors in different laboratories. Clinical CYP3A induction and in
vitro data were gathered for 51 compounds, 16 of which were proprietary. A large
degree of variability was observed in both the clinical and in vitro induction
responses; however, analysis confirmed in vitro data are able to predict clinical
induction risk. Following extensive examination of this large data set, the
following recommendations are proposed. a) Cytochrome P450 induction should
continue to be evaluated in three separate human donors in vitro. b) In light of
empirically divergent responses in rifampicin control and most test inducers,
normalization of data to percent positive control appears to be of limited
benefit. c) With concentration dependence, 2-fold induction is an acceptable
threshold for positive identification of in vitro CYP3A4 mRNA induction. d) To
reduce the risk of false positives, in the absence of a concentration-dependent
response, induction >= 2-fold should be observed in more than one donor to
classify a compound as an in vitro inducer. e) If qualifying a compound as
negative for CYP3A4 mRNA induction, the magnitude of maximal rifampicin response
in that donor should be >= 10-fold. f) Inclusion of a negative control adds no
value beyond that of the vehicle control.
PMID- 29959134
TI - Glycyrrhizin Alleviates Nonalcoholic Steatohepatitis via Modulating Bile Acids
and Meta-Inflammation.
AB - Nonalcoholic steatohepatitis (NASH) is the progressive stage of nonalcoholic
fatty liver disease that may ultimately lead to cirrhosis and liver cancer, and
there are few therapeutic options for its treatment. Glycyrrhizin (GL), extracted
from the traditional Chinese medicine liquorice, has potent hepatoprotective
effects in both preclinical animal models and in humans. However, little is
currently known about its effects and mechanisms in treating NASH. To explore the
effects of GL on NASH, GL or its active metabolite glycyrrhetinic acid (GA) was
administered to mice treated with a methionine- and choline-deficient (MCD) diet
induced NASH model, and histologic and biochemical analyses were used to measure
the degree of lipid disruption, liver inflammation, and fibrosis. GL
significantly improved MCD diet-induced hepatic steatosis, inflammation, and
fibrosis and inhibited activation of the NLR family pyrin domain-containing 3
(NLRP3) inflammasome. GL significantly attenuated serum bile acid accumulation in
MCD diet-fed mice partially by restoring inflammation-mediated hepatic farnesoid
X receptor inhibition. In Raw 264.7 macrophage cells, both GL and GA inhibited
deoxycholic acid-induced NLRP3 inflammasome-associated inflammation. Notably,
both intraperitoneal injection of GL's active metabolite GA and oral
administration of GL prevented NASH in mice, indicating that GL may attenuate
NASH via its active metabolite GA. These results reveal that GL, via restoration
of bile acid homeostasis and inhibition of inflammatory injury, can be a
therapeutic option for treatment of NASH.
PMID- 29959135
TI - Match injury incidence during the Super Rugby tournament is high: a prospective
cohort study over five seasons involving 93 641 player-hours.
AB - OBJECTIVES: To determine the incidence and nature of injuries in the Super Rugby
tournament over a 5-year period. METHODS: 482 male professional rugby union
players from six South African teams participating in the Super Rugby tournament
were studied (1020 player-seasons). Medical staff of participating teams (2012
2016 tournaments) recorded all time loss injuries (total injuries and match
injuries) and exposure hours (93 641 total playing hours; 8032 match hours).
Injury incidence, injured player proportion, severity (time lost), anatomical
location, tissue type and activity/phase during which injury occurred are
reported. RESULTS: The overall incidence of match injuries (per 1000 player
hours; 95% CI) for each year was as follows: 2012 (83.3; 69.4-99.2); 2013 (115.1;
98.7-133.5); 2014 (95.9; 80.8-113.1), 2015 (112.3; 96.6-129.9) and 2016 (93.2;
79.9-107.9). The injured player proportion for each year was as follows: 2012
(54.6%); 2013 (49.4%); 2014 (52.0%); 2015 (50.0%); and 2016 (39.8%). The thigh,
knee, head/face and shoulder/clavicle are the most frequently injured locations,
and muscle/tendon and joint/ligament injuries account for the majority of
injuries. Most injuries (79%) occur in contact situations, in particular during a
tackle (54%). CONCLUSION: The incidence of match injuries and the injured player
proportion in South African teams competing in the Super Rugby tournament is
high. Match injury incidence is consistently higher than previously reported for
senior male rugby players at elite/professional level. Targeted risk management
strategies are therefore needed in the Super Rugby tournament to manage risk of
injury.
PMID- 29959136
TI - Bioimpedance and New-Onset Heart Failure: A Longitudinal Study of >500 000
Individuals From the General Population.
AB - BACKGROUND: Heart failure constitutes a high burden on patients and society, but
although lifetime risk is high, it is difficult to predict without costly or
invasive testing. We aimed to establish new risk factors of heart failure, which
potentially could enable early diagnosis and preemptive treatment. METHODS AND
RESULTS: We applied machine learning in the UK Biobank in an agnostic search of
risk factors for heart failure in 500 451 individuals, excluding individuals with
prior heart failure. Novel factors were then subjected to several in-depth
analyses, including multivariable Cox models of incident heart failure, and
assessment of discrimination and calibration. Machine learning confirmed many
known and putative risk factors for heart failure and identified several novel
candidates. Mean reticulocyte volume appeared as one novel factor and leg
bioimpedance another, the latter appearing as the most important new marker. Leg
bioimpedance was lower in those who developed heart failure during an up to 9.8
year follow-up. When adjusting for known heart failure risk factors, leg
bioimpedance was inversely related to heart failure (hazard ratio [95% confidence
interval], 0.60 [0.48-0.73] and 0.75 [0.59-0.94], in age- and sex-adjusted and
fully adjusted models, respectively, comparing the upper versus lower quartile).
A model including leg bioimpedance, age, sex, and self-reported history of
myocardial infarction showed good discrimination for future heart failure
hospitalization (Concordance index [C-index]=0.82) and good calibration.
CONCLUSIONS: Leg bioimpedance is inversely associated with heart failure
incidence in the general population. A simple model of exclusively noninvasive
measures, combining leg bioimpedance with history of myocardial infarction, age,
and sex provides accurate predictive capacity.
PMID- 29959137
TI - Predominant Role of Nuclear Versus Membrane Estrogen Receptor alpha in Arterial
Protection: Implications for Estrogen Receptor alpha Modulation in Cardiovascular
Prevention/Safety.
AB - BACKGROUND: Although estrogen receptor alpha (ERalpha) acts primarily as a
transcription factor, it can also elicit membrane-initiated steroid signaling.
Pharmacological tools and transgenic mouse models previously highlighted the key
role of ERalpha membrane-initiated steroid signaling in 2 actions of estrogens in
the endothelium: increase in NO production and acceleration of
reendothelialization. METHODS AND RESULTS: Using mice with ERalpha mutated at
cysteine 451 (ERaC451A), recognized as the key palmitoylation site required for
ERalpha plasma membrane location, and mice with disruption of nuclear actions
because of inactivation of activation function 2 (ERaAF20 = ERaAF2 degrees ), we
sought to fully characterize the respective roles of nuclear versus membrane
initiated steroid signaling in the arterial protection conferred by ERalpha.
ERaC451A mice were fully responsive to estrogens to prevent atheroma and
angiotensin II-induced hypertension as well as to allow flow-mediated arteriolar
remodeling. By contrast, ERalphaAF20 mice were unresponsive to estrogens for
these beneficial vascular effects. Accordingly, selective activation of nuclear
ERalpha with estetrol was able to prevent hypertension and to restore flow
mediated arteriolar remodeling. CONCLUSIONS: Altogether, these results reveal an
unexpected prominent role of nuclear ERalpha in the vasculoprotective action of
estrogens with major implications in medicine, particularly for selective nuclear
ERalpha agonist, such as estetrol, which is currently under development as a new
oral contraceptive and for hormone replacement therapy in menopausal women.
PMID- 29959139
TI - Looking for CO2: Exploring the Novel Finding of Low Respiratory Quotient After
Cardiac Arrest.
PMID- 29959138
TI - Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post-Cardiac
Arrest Rat: A Novel Metabolic Phenotype.
AB - BACKGROUND: The concept that resuscitation from cardiac arrest (CA) results in a
metabolic injury is broadly accepted, yet patients never receive this diagnosis.
We sought to find evidence of metabolic injuries after CA by measuring O2
consumption and CO2 production (VCO2) in a rodent model. In addition, we tested
the effect of inspired 100% O2 on the metabolism. METHODS AND RESULTS: Rats were
anesthetized and randomized into 3 groups: resuscitation from 10-minute asphyxia
with inhaled 100% O2 (CA-fraction of inspired O2 [FIO2] 1.0), with 30% O2 (CA
FIO2 0.3), and sham with 30% O2 (sham-FIO2 0.3). Animals were resuscitated with
manual cardiopulmonary resuscitation. The volume of extracted O2 (VO2) and VCO2
were measured for a 2-hour period after resuscitation. The respiratory quotient
(RQ) was RQ=VCO2/VO2. VCO2 was elevated in CA-FIO2 1.0 and CA-FIO2 0.3 when
compared with sham-FIO2 0.3 in minutes 5 to 40 after resuscitation (CA-FIO2 1.0:
16.7+/-2.2, P<0.01; CA-FIO2 0.3: 17.4+/-1.4, P<0.01; versus sham-FIO2 0.3: 13.6+/
1.1 mL/kg per minute), and then returned to normal. VO2 in CA-FIO2 1.0 and CA
FIO2 0.3 increased gradually and was significantly higher than sham-FIO2 0.3 2
hours after resuscitation (CA-FIO2 1.0: 28.7+/-6.7, P<0.01; CA-FIO2 0.3: 24.4+/
2.3, P<0.01; versus sham-FIO2 0.3: 15.8+/-2.4 mL/kg per minute). The RQ of CA
animals persistently decreased (CA-FIO2 1.0: 0.54+/-0.12 versus CA-FIO2 0.3:
0.68+/-0.05 versus sham-FIO2 0.3: 0.93+/-0.11, P<0.01 overall). CONCLUSIONS: CA
altered cellular metabolism resulting in increased VO2 with normal VCO2. Normal
VCO2 suggests that the postresuscitation Krebs cycle is operating at a presumably
healthy rate. Increased VO2 in the face of normal VCO2 suggests a significant
alteration in O2 utilization in postresuscitation. Several RQ values fell well
outside the normally cited range of 0.7 to 1.0. Higher FIO2 may increase VO2,
leading to even lower RQ values.
PMID- 29959140
TI - Skeletal Muscle Loss Is an Imaging Biomarker of Outcome after Definitive
Chemoradiotherapy for Locally Advanced Cervical Cancer.
AB - Purpose: This study investigates the association between body composition change
during concurrent chemoradiotherapy (CCRT) and outcome in patients with locally
advanced cervical cancer (LACC).Experimental Design: Pre- and posttreatment CT
images of 245 patients with LACC who were treated between 2004 and 2015 were
analyzed. Skeletal muscle index (SMI) and density (SMD), subcutaneous adipose
tissue index (SATI), and visceral adipose tissue index (VATI) were measured from
two sets of CT images at the level of the L3 vertebra. Sarcopenia and a low SMD
were defined using published cut-off points. Predictors of overall survival (OS)
and cancer-specific survival (CSS) were analyzed using Cox regression
models.Results: The median follow-up was 62.7 (range, 7.3-152.3) months. Among
the 245 patients, 127 (51.8%) had pretreatment sarcopenia, and 154 (62.9%) had a
low SMD. SMI did not decrease significantly during CCRT, 0.6%/150 days [95%
confidence interval (CI), -1.8-0.6; P = 0.35]. However, SMI loss during CCRT of
>10.0%/150 days was independently associated with poorer OS (HR, 6.02; 95% CI,
3.04-11.93; P < 0.001) and CSS (HR, 3.49; 95% CI, 1.44-8.42; P = 0.006) when
adjusted for FIGO stage, pathology, and treatment. Pretreatment sarcopenia and
change of SMD, SATI, and VATI during CCRT were not associated with
survival.Conclusions: Skeletal muscle measurements could be imaging biomarkers to
predict outcomes for patients with LACC in clinical practice. Further studies are
needed to determine whether multimodal interventions can preserve skeletal muscle
mass and thereby improve survival. Clin Cancer Res; 24(20); 5028-36. (c)2018
AACR.
PMID- 29959142
TI - Cancer-Stimulated CAFs Enhance Monocyte Differentiation and Protumoral TAM
Activation via IL6 and GM-CSF Secretion.
AB - Purpose: M2-type TAMs are increasingly implicated as a crucial factor promoting
metastasis. Numerous cell types dictate monocyte differentiation into M2 TAMs via
a complex network of cytokine-based communication. Elucidating critical pathways
in this network can provide new targets for inhibiting metastasis. In this study,
we focused on cancer cells, CAFs, and monocytes as a major node in this
network.Experimental Design: Monocyte cocultures with cancer-stimulated CAFs were
used to investigate differentiation into M2-like TAMs. Cytokine array analyses
were employed to discover the CAF-derived regulators of differentiation. These
regulators were validated in primary CAFs and bone marrow-derived monocytes.
Orthotopic, syngeneic colon carcinoma models using cotransplanted CAFs were
established to observe effects on tumor growth and metastasis. To confirm a
correlation with clinical evidence, meta-analyses were employed using the
Oncomine database.Results: Our coculture studies identify IL6 and GM-CSF as the
pivotal signals released from cancer cell-activated CAFs that cooperate to induce
monocyte differentiation into M2-like TAMs. In orthotopic, syngeneic colon
carcinoma mouse models, cotransplanted CAFs elevated IL6 and GM-CSF levels, TAM
infiltration, and metastasis. These pathologic effects were dramatically reversed
by joint IL6 and GM-CSF blockade. A positive correlation between GM-CSF and IL6
expression and disease course was observed by meta-analyses of the clinical
data.Conclusions: Our studies indicate a significant reappraisal of the role of
IL6 and GM-CSF in metastasis and implicate CAFs as the "henchmen" for cancer
cells in producing an immunosuppressive tumor ecological niche. Dual targeting of
GM-CSF and IL6 is a promising new approach for inhibiting metastasis. Clin Cancer
Res; 24(21); 5407-21. (c)2018 AACR.
PMID- 29959141
TI - Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular
Morphology in Preclinical Tumors and in Human Liver Metastases.
AB - Purpose: Tumor vessels influence the growth and response of tumors to therapy.
Imaging vascular changes in vivo using dynamic contrast-enhanced MRI (DCE-MRI)
has shown potential to guide clinical decision making for treatment. However,
quantitative MR imaging biomarkers of vascular function have not been widely
adopted, partly because their relationship to structural changes in vessels
remains unclear. We aimed to elucidate the relationships between vessel function
and morphology in vivo Experimental Design: Untreated preclinical tumors with
different levels of vascularization were imaged sequentially using DCE-MRI and
CT. Relationships between functional parameters from MR (iAUC, K trans, and
BATfrac) and structural parameters from CT (vessel volume, radius, and
tortuosity) were assessed using linear models. Tumors treated with anti-VEGFR2
antibody were then imaged to determine whether antiangiogenic therapy altered
these relationships. Finally, functional-structural relationships were measured
in 10 patients with liver metastases from colorectal cancer.Results: Functional
parameters iAUC and K trans primarily reflected vessel volume in untreated
preclinical tumors. The relationships varied spatially and with tumor
vascularity, and were altered by antiangiogenic treatment. In human liver
metastases, all three structural parameters were linearly correlated with iAUC
and K trans For iAUC, structural parameters also modified each other's
effect.Conclusions: Our findings suggest that MR imaging biomarkers of vascular
function are linked to structural changes in tumor vessels and that
antiangiogenic therapy can affect this link. Our work also demonstrates the
feasibility of three-dimensional functional-structural validation of MR
biomarkers in vivo to improve their biological interpretation and clinical
utility. Clin Cancer Res; 24(19); 4694-704. (c)2018 AACR.
PMID- 29959143
TI - An Anti-CLL-1 Antibody-Drug Conjugate for the Treatment of Acute Myeloid
Leukemia.
AB - PURPOSE: The treatment of acute myeloid leukemia (AML) has not significantly
changed in 40 years. Cytarabine and anthracycline-based chemotherapy induction
regimens (7 + 3) remain the standard of care, and most patients have poor long
term survival. The re-approval of Mylotarg, an anti-CD33-calicheamicin antibody
drug conjugate (ADC), has demonstrated ADCs as a clinically validated option to
enhance the effectiveness of induction therapy. We are interested in developing a
next generation ADC for AML to improve upon the initial success of Mylotarg.
EXPERIMENTAL DESIGN: The expression pattern of CLL-1 and its hematopoietic
potential were investigated. A novel anti-CLL-1-ADC, with a highly potent
pyrrolobenzodiazepine (PBD) dimer conjugated through a self-immolative disulfide
linker, was developed. The efficacy and safety profiles of this ADC were
evaluated in mouse xenograft models and in cynomolgus monkeys. RESULTS: We
demonstrate that CLL-1 shares similar prevalence and trafficking properties that
make CD33 an excellent ADC target for AML, but lacks expression on hematopoietic
stem cells that hampers current CD33 targeted ADCs. Our anti-CLL-1-ADC is highly
effective at depleting tumor cells in AML xenograft models and lacks target
independent toxicities at doses that depleted target monocytes and neutrophils in
cynomolgus monkeys. CONCLUSIONS: Collectively, our data suggest that an anti-CLL
1-ADC has the potential to become an effective and safer treatment for AML in
humans, by reducing and allowing for faster recovery from initial cytopenias than
the current generation of ADCs for AML.
PMID- 29959144
TI - Dual Src and MEK Inhibition Decreases Ovarian Cancer Growth and Targets Tumor
Initiating Stem-Like Cells.
AB - Purpose: Rational targeted therapies are needed for treatment of ovarian cancers.
Signaling kinases Src and MAPK are activated in high-grade serous ovarian cancer
(HGSOC). Here, we tested the frequency of activation of both kinases in HGSOC and
the therapeutic potential of dual kinase inhibition.Experimental Design: MEK and
Src activation was assayed in primary HGSOC from The Cancer Genome Atlas (TGGA).
Effects of dual kinase inhibition were assayed on cell-cycle, apoptosis, gene,
and proteomic analysis; cancer stem cells; and xenografts.Results: Both Src and
MAPK are coactivated in 31% of HGSOC, and this associates with worse overall
survival on multivariate analysis. Frequent dual kinase activation in HGSOC led
us to assay the efficacy of combined Src and MEK inhibition. Treatment of
established lines and primary ovarian cancer cultures with Src and MEK inhibitors
saracatinib and selumetinib, respectively, showed target kinase inhibition and
synergistic induction of apoptosis and cell-cycle arrest in vitro, and tumor
inhibition in xenografts. Gene expression and proteomic analysis confirmed cell
cycle inhibition and autophagy. Dual therapy also potently inhibited tumor
initiating cells. Src and MAPK were both activated in tumor-initiating
populations. Combination treatment followed by drug washout decreased sphere
formation and ALDH1+ cells. In vivo, tumors dissociated after dual therapy showed
a marked decrease in ALDH1 staining, sphere formation, and loss of tumor
initiating cells upon serial xenografting.Conclusions: Selumetinib added to
saracatinib overcomes EGFR/HER2/ERBB2-mediated bypass activation of MEK/MAPK
observed with saracatinib alone and targets tumor-initiating ovarian cancer
populations, supporting further evaluation of combined Src-MEK inhibition in
clinical trials. Clin Cancer Res; 24(19); 4874-86. (c)2018 AACR.
PMID- 29959145
TI - Development and evaluation of percentile distribution of body weight by
gestational week as a tool for gestational weight management: a retrospective
study based on hospital routine data.
AB - OBJECTIVES: This study aimed to construct and validate smoothed gestational
weight centile curves based on preconception weight status for Chinese pregnant
women. DESIGN: A retrospective study based on hospital routine data SETTING:
Hospital prenatal care. POPULATION: A cohort of pregnant Chinese women with
preconception and gestational body weights without maternal or neonatal
complications (sample 1, n=2992), and a non-selective independent sample (sample
2, n=7420), were selected from hospital routine data for curve construction and
validation. STUDY DESIGN: Smoothed body weight centile curves for each
gestational week were constructed using the LMS method in sample 1. Validation in
sample 2 included analysis of agreement between predicted weight at the 38th week
and observed values using the Bland-Altman Index. Predictions were also compared
with international curves. RESULTS: Smoothed centile curves of gestational weight
for the three preconception body mass index groups showed a similar non-linear
increasing trend. The differences between predicted body weights and observed
values were 0.66+/-1.58 kg, 0.14+/-1.61 kg and -0.54+/-2.06 kg in the
underweight, normal weight and overweight groups, respectively. Bland-Altman
Index values were 5.2%, 5.6% and 4.7% in the underweight, normal weight and
overweight groups, respectively, with limits of agreement of -2.4~3.8 kg,
3.0~3.3 kg and -4.4~3.4 kg, respectively. These limits of agreement were narrower
than those of available international curves. CONCLUSION: Body weight percentiles
for gestational weeks 0-42 were proposed for underweight, normal weight or
overweight Chinese women. These curves could constitute a useful tool for
individualised gestational weight management by predicting body weight at a later
gestation phase.
PMID- 29959146
TI - Continuity of care with doctors-a matter of life and death? A systematic review
of continuity of care and mortality.
AB - OBJECTIVE: Continuity of care is a long-standing feature of healthcare,
especially of general practice. It is associated with increased patient
satisfaction, increased take-up of health promotion, greater adherence to medical
advice and decreased use of hospital services. This review aims to examine
whether there is a relationship between the receipt of continuity of doctor care
and mortality. DESIGN: Systematic review without meta-analysis. DATA SOURCES:
MEDLINE, Embase and the Web of Science, from 1996 to 2017. ELIGIBILITY CRITERIA
FOR SELECTING STUDIES: Peer-reviewed primary research articles, published in
English which reported measured continuity of care received by patients from any
kind of doctor, in any setting, in any country, related to measured mortality of
those patients. RESULTS: Of the 726 articles identified in searches, 22 fulfilled
the eligibility criteria. The studies were all cohort or cross-sectional and most
adjusted for multiple potential confounding factors. These studies came from nine
countries with very different cultures and health systems. We found such
heterogeneity of continuity and mortality measurement methods and time frames
that it was not possible to combine the results of studies. However, 18 (81.8%)
high-quality studies reported statistically significant reductions in mortality,
with increased continuity of care. 16 of these were with all-cause mortality.
Three others showed no association and one demonstrated mixed results. These
significant protective effects occurred with both generalist and specialist
doctors. CONCLUSIONS: This first systematic review reveals that increased
continuity of care by doctors is associated with lower mortality rates. Although
all the evidence is observational, patients across cultural boundaries appear to
benefit from continuity of care with both generalist and specialist doctors. Many
of these articles called for continuity to be given a higher priority in
healthcare planning. Despite substantial, successive, technical advances in
medicine, interpersonal factors remain important. PROSPERO REGISTRATION NUMBER:
CRD42016042091.
PMID- 29959147
TI - Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of
Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a
DOPPLER-CIP Substudy.
AB - BACKGROUND: Cardiac troponin T concentrations measured with high-sensitivity
assays (hs-cTnT) provide important prognostic information for patients with
stable coronary artery disease (CAD). However, whether hs-cTnT concentrations
mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia
in this population is not known. METHODS: We measured hs-cTnT concentrations in
619 subjects with suspected stable CAD in a prospectively designed multicenter
study. We identified associations with indices of LV remodeling, as assessed by
cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed
by single positron emission computed tomography. RESULTS: Median hs-cTnT
concentration was 7.8 ng/L (interquartile range, 4.8-11.6 ng/L), and 111 patients
(18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L).
Patients with hs-cTnT >14 ng/L had increased LV mass (144 +/- 40 g vs 116 +/- 34
g; P < 0.001) and volume (179 +/- 80 mL vs 158 +/- 44 mL; P = 0.006), lower LV
ejection fraction (LVEF) (59 +/- 14 vs 62 +/- 11; P = 0.006) and global
longitudinal strain (14.1 +/- 3.4% vs 16.9 +/- 3.2%; P < 0.001), and more
reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities
(P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV
mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia
(P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all
associated with increasing hs-cTnT concentrations in multivariate analysis. We
found analogous results when using the revised US upper reference limit of 19
ng/L. CONCLUSIONS: hs-cTnT concentrations reflect both LV mass and reversible
myocardial ischemia in patients with suspected stable CAD.
PMID- 29959148
TI - External Quality Assessment Testing Near the Limit of Detection for High
Sensitivity Cardiac Troponin Assays.
PMID- 29959149
TI - LIFEx: A Freeware for Radiomic Feature Calculation in Multimodality Imaging to
Accelerate Advances in the Characterization of Tumor Heterogeneity.
AB - Textural and shape analysis is gaining considerable interest in medical imaging,
particularly to identify parameters characterizing tumor heterogeneity and to
feed radiomic models. Here, we present a free, multiplatform, and easy-to-use
freeware called LIFEx, which enables the calculation of conventional, histogram
based, textural, and shape features from PET, SPECT, MR, CT, and US images, or
from any combination of imaging modalities. The application does not require any
programming skills and was developed for medical imaging professionals. The goal
is that independent and multicenter evidence of the usefulness and limitations of
radiomic features for characterization of tumor heterogeneity and subsequent
patient management can be gathered. Many options are offered for interactive
textural index calculation and for increasing the reproducibility among centers.
The software already benefits from a large user community (more than 800
registered users), and interactions within that community are part of the
development strategy.Significance: This study presents a user-friendly, multi
platform freeware to extract radiomic features from PET, SPECT, MR, CT, and US
images, or any combination of imaging modalities. Cancer Res; 78(16); 4786-9.
(c)2018 AACR.
PMID- 29959150
TI - Pathology, Chemoprevention, and Preclinical Models for Target Validation in
Barrett Esophagus.
AB - Despite esophageal adenocarcinoma (EAC) being the most widespread among
gastrointestinal cancers, with an 11-fold increase in the risk of cancer for
patients with Barrett esophagus (BE), its prognosis is still poor. There is a
critical need to better perceive the biology of cancer progression and
identification of specific targets that are the hallmark of BE's progression.
This review explores the established animal models of BE, including genetic,
surgical and nonsurgical approaches, potential chemoprevention targets, and the
reasoning behind their applications to prevent Barrett-related EAC. The key
methodological features in the design feasibility of relevant studies are also
discussed. Cancer Res; 78(14); 3747-54. (c)2018 AACR.
PMID- 29959151
TI - Cyclophilin A Function in Mammary Epithelium Impacts Jak2/Stat5 Signaling,
Morphogenesis, Differentiation, and Tumorigenesis in the Mammary Gland.
AB - The prolyl isomerase cyclophilin A (CypA) regulates the Jak2/Stat5 pathway, which
is necessary for mammary differentiation and the pathogenesis of breast cancer.
In this study, we assessed the role of this isomerase during mammary gland
development and erbB2-driven tumorigenesis. Genetic deletion of CypA resulted in
delayed mammary gland morphogenesis and differentiation with corresponding
decrease in Jak2/Stat5 activation; mammary gland cross-transplantation confirmed
this defect was epithelial in nature. Analysis of mammary stem and progenitor
populations revealed significant disruption of epithelial maturation. Loss of
CypA in the erbB2 transgenic mouse model revealed a marked increase in mammary
tumor latency that correlated with decreased Stat5 activation, associated gene
expression, and reduced epithelial cell proliferation. These results demonstrate
an important role for CypA in the regulation of Jak2/Stat5-mediated biology in
mammary epithelium, identifying this isomerase as a novel target for therapeutic
intervention.Significance: These findings reveal cyclophilin A functions in
normal mammary epithelial development and ErbB2-driven mammary tumorigenesis and
suggest therapies targeting cyclophilin A may be efficacious for breast cancer
treatment.Graphical Abstract:
http://cancerres.aacrjournals.org/content/canres/78/14/3877/F1.large.jpg Cancer
Res; 78(14); 3877-87. (c)2018 AACR.
PMID- 29959153
TI - Man with advanced MND vows to keep fighting for assisted death after losing case
in Court of Appeal.
PMID- 29959152
TI - Low-dose cytarabine to prevent myeloid leukemia in children with Down syndrome:
TMD Prevention 2007 study.
AB - Approximately 5% to 10% of children with Down syndrome (DS) are diagnosed with
transient myeloproliferative disorder (TMD). Approximately 20% of these patients
die within 6 months (early death), and another 20% to 30% progress to myeloid
leukemia (ML-DS) within their first 4 years of life. The aim of the multicenter,
nonrandomized, historically controlled TMD Prevention 2007 trial was to evaluate
the impact of low-dose cytarabine treatment on survival and prevention of ML-DS
in patients with TMD. Patients received cytarabine (1.5 mg/kg for 7 days) in case
of TMD-related symptoms at diagnosis (high white blood cell count, ascites, liver
dysfunction, hydrops fetalis) or detection of minimal residual disease (MRD) 8
weeks after diagnosis. The 5-year probability of event-free and overall survival
of 102 enrolled TMD patients was 72 +/- 5% and 91 +/- 3%, respectively. In
patients eligible for treatment because of symptoms (n = 43), we observed a
significantly lower cumulative incidence (CI) of early death as compared with
symptomatic patients in the historical control (n = 45) (12 +/- 5% vs 33 +/- 7%,
PGray = .02). None of the asymptomatic patients in the current study suffered
early death. However, the treatment of symptomatic or MRD-positive patients did
not result in a significantly lower CI of ML-DS (25 +/- 7% [treated] vs 14 +/- 7%
[untreated], PGray = .34 [per protocol analysis]; historical control: 22 +/- 4%,
PGray = .55). Thus, low-dose cytarabine treatment helped to reduce TMD-related
mortality when compared with the historical control but was insufficient to
prevent progression to ML-DS. This trial was registered at EudraCT as #2006
002962-20.
PMID- 29959154
TI - There is a linear association between decreasing Apgar scores at 5 and 10 min and
adverse neurodevelopmental outcomes.
PMID- 29959155
TI - Edoxaban is non-inferior to low-molecular-weight heparin for treating cancer
associated venous thromboembolism.
PMID- 29959156
TI - Can the NHS be a learning healthcare system in the age of digital technology?
PMID- 29959157
TI - Trimethoprim is associated with a greater risk of acute kidney injury and
hyperkalaemia in older adults compared with other antibiotics used to treat UTIs.
PMID- 29959159
TI - Commonly used approach for multimorbidity fails to improve quality of life.
PMID- 29959158
TI - A word about evidence: 'rapid reviews' or 'restricted reviews'?
PMID- 29959162
TI - The Histone Demethylase LSD1 Inhibits Tumor Cell Immunogenicity.
AB - Loss of LSD1 enhances tumor immunogenicity and sensitizes refractory mouse
melanoma to anti-PD-1 therapy.
PMID- 29959161
TI - Restoration of 5-hydroxymethylcytosine by ascorbate blocks kidney tumour growth.
AB - Loss of 5-hydroxymethylcytosine (5hmC) occurs frequently in a wide variety of
tumours, including clear-cell renal cell carcinoma (ccRCC). It remains unknown,
however, whether the restoration of 5hmC patterns in tumours could have
therapeutic efficacy. Here, we used sodium L-ascorbate (vitamin C, AsANa) and the
oxidation-resistant form L-ascorbic acid 2-phosphate sesquimagnesium (APM) for
the restoration of 5hmC patterns in ccRCC cells. At physiological concentrations,
both show anti-tumour efficacy during long-term treatment in vitro and in vivo
Strikingly, global 5hmC patterns in ccRCC cells after treatment resemble those of
normal kidney tissue, which is observed also in treated xenograft tumours, and in
primary cells from a ccRCC patient. Further, RNA-seq data show that long-term
treatment with vitamin C changes the transcriptome of ccRCC cells. Finally, APM
treatment induces less non-specific cell damage and shows increased stability in
mouse plasma compared to AsANa. Taken together, our study provides proof of
concept for an epigenetic differentiation therapy of ccRCC with vitamin C,
especially APM, at low doses by 5hmC reprogramming.
PMID- 29959160
TI - Reappraisal of Reported Genes for Sudden Arrhythmic Death.
AB - BACKGROUND: Implicit in the genetic evaluation of patients with suspected genetic
diseases is the assumption that the genes evaluated are causative for the disease
based on robust scientific and statistical evidence. However, in the past 20
years, considerable variability has existed in the study design and quality of
evidence supporting reported gene-disease associations, raising concerns of the
validity of many published disease-causing genes. Brugada syndrome (BrS) is an
arrhythmia syndrome with a risk of sudden death. More than 20 genes have been
reported to cause BrS and are assessed routinely on genetic testing panels in the
absence of a systematic, evidence-based evaluation of the evidence supporting the
causality of these genes. METHODS: We evaluated the clinical validity of genes
tested by diagnostic laboratories for BrS by assembling 3 gene curation teams.
Using an evidence-based semiquantitative scoring system of genetic and
experimental evidence for gene-disease associations, curation teams independently
classified genes as demonstrating limited, moderate, strong, or definitive
evidence for disease causation in BrS. The classification of curator teams was
reviewed by a clinical domain expert panel that could modify the classifications
based on their independent review and consensus. RESULTS: Of 21 genes curated for
clinical validity, biocurators classified only 1 gene ( SCN5A) as definitive
evidence, whereas all other genes were classified as limited evidence. After
comprehensive review by the clinical domain Expert panel, all 20 genes classified
as limited evidence were reclassified as disputed with regard to any assertions
of disease causality for BrS. CONCLUSIONS: Our results contest the clinical
validity of all but 1 gene clinically tested and reported to be associated with
BrS. These findings warrant a systematic, evidence-based evaluation for reported
gene-disease associations before use in patient care.
PMID- 29959163
TI - Transcription Factor Low-Complexity Domain Hubs Drive Transcription.
AB - Low-complexity domains (LCD) in transcription factors can form high-concentration
interaction hubs.
PMID- 29959164
TI - Enzymes That Catalyze Wobble tRNA Modification Promote Melanomagenesis.
AB - Enzymes that modify wobble uridine 34 tRNAs (U34 enzymes) maintain HIF1alpha
levels in BRAFV600E melanoma.
PMID- 29959165
TI - Phase Separation Concentrates Transcription Proteins at Superenhancers.
AB - Intrinsically disordered regions of MED1 and BRD4 promote formation of phase
separated condensates.
PMID- 29959166
TI - Allow English women to take medical abortion pill at home, say doctors.
PMID- 29959167
TI - Meningitis: UK adults face diagnosis delays and inappropriate treatment, study
finds.
PMID- 29959168
TI - Multiple HBV transfusion transmissions from undetected occult infections:
revising the minimal infectious dose.
AB - OBJECTIVE: HBV infection by blood components is currently prevented in most
developed countries by combining sensitive HBV surface antigen (HBsAg) assays,
nucleic acid testing (NAT) and in a few of them antibodies against the HBV core
antigen (anti-HBc) screening. HBV transmissions by blood components from three
repeat donors tested negative for HBsAg and HBV DNA with a highly sensitive
screening test (limit of detection (LOD): 3.4 IU/mL) were investigated. DESIGN:
30 of the 47 recipients of components produced from these three donors were
examined. Transfusion transmission was confirmed by phylogenetic analysis of
viral sequences obtained from recipients and donors following viral particle
concentration. RESULTS: 9 of 31 (29%) recipients were infected: 7 infections were
related to 200 mL of fresh frozen plasma and 2 infections to red blood cells
containing 20 mL plasma. Transfusion transmission was confirmed by >99% identity
of donor/recipient sequences in five cases, probable in three and possible in
one. HBV active infection remained unsuspected for 24-57 months in three
recipients. Five non-infected recipients carried anti-HBs when transfused. Six
patients transfused with platelet concentrates treated with a pathogen reduction
method were not infected. These data enabled to revise previous estimate of the
minimal infectious dose from approximately 100 to 16 copies (or 3 IU) of HBV DNA.
CONCLUSIONS: HBV transfusion transmission from occult HBV infection carrying
extremely low viral loads is related to plasma volume transfused and possibly
prevented by anti-HBs. HBV blood safety could be further improved by either anti
HBc screening, HBV DNA NAT with a LOD of 0.8 copies/mL (0.15 IU/mL) or pathogen
reduction of blood components.
PMID- 29959169
TI - What is required from HCV point-of-care tests to reduce the burden of hepatitis C
infection? 'Development and clinical validation of the genedrive point-of-care
test for qualitative detection of hepatitis C virus'.
PMID- 29959170
TI - All four subunits of HCN2 channels contribute to the activation gating in an
additive but intricate manner.
AB - Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are
tetramers that elicit electrical rhythmicity in specialized brain neurons and
cardiomyocytes. The channels are dually activated by voltage and binding of
cyclic adenosine monophosphate (cAMP) to their four cyclic nucleotide-binding
domains (CNBDs). Here we analyze the effects of cAMP binding to different
concatemers of HCN2 channel subunits, each having a defined number of functional
CNBDs. We show that each liganded CNBD promotes channel activation in an additive
manner and that, in the special case of two functional CNBDs, functionality does
not depend on the arrangement of the subunits. Correspondingly, the reverse
process of deactivation is slowed by progressive liganding, but only if four and
three ligands as well as two ligands in trans position (opposite to each other)
are bound. In contrast, two ligands bound in cis positions (adjacent to each
other) and a single bound ligand do not affect channel deactivation. These
results support an activation mechanism in which each single liganded CNBD causes
a turning momentum on the tetrameric ring-like structure formed by all four CNBDs
and that at least two liganded subunits in trans positions are required to
maintain activation.
PMID- 29959171
TI - Evidence for Exaptation of the Marchantia polymorpha M20D Peptidase MpILR1 into
the Tracheophyte Auxin Regulatory Pathway.
AB - Auxin homeostasis is tightly regulated by several mechanisms, including
conjugation of the hormone to specific moieties, such as amino acids or sugar.
The inactive phytohormone conjugate is stored in large pools in plants and
hydrolyzed to regain full activity. Many conjugate hydrolases (M20D
metallopeptidases) have been identified and characterized throughout the plant
kingdom. We have traced this regulatory gene family back to liverwort (Marchantia
polymorpha), a member of the most ancient extant land plant lineage, which
emerged approximately 475 million years ago. We have isolated and characterized a
single hydrolase homologue, dubbed M. polymorpha IAA-Leucine Resistant1 (MpILR1),
from liverwort. MpILR1 can hydrolyze two auxin (indole acetic acid [IAA])
substrates (IAA-Leucine and IPA-Alanine) at very low levels of activity, but it
cannot hydrolyze the two native auxin conjugates of liverwort (IAA-Glycine and
IAA-Valine). We conclude from these results that liverwort likely does not employ
active auxin conjugate hydrolysis as a regulatory mechanism and that conjugate
homeostasis likely takes place in liverwort by passive background degradation.
Furthermore, we present evidence that MpILR1 was probably exapted by
tracheophytes over evolutionary time into the auxin regulatory pathway.
PMID- 29959172
TI - Tuberculous arthritis: negative Xpert MTB/RIF assay does not rule out infection!
AB - We present a case of a 31-year-old man of Indian origin with no previous medical
history who presented with an inflamed knee. Treatment for bacterial infection
was unsuccessful, and needle aspiration of the left knee effusion/collection was
smear and culture positive for tuberculosis (TB), despite Xpert MTB/RIF being
falsely negative. The patient was commenced on quadruple therapy for TB and
within 2 months had improved significantly with no clinical evidence of ongoing
inflammation.
PMID- 29959173
TI - A splenic IgM memory subset with antibacterial specificities is sustained from
persistent mucosal responses.
AB - To what extent immune responses against the gut flora are compartmentalized
within mucosal tissues in homeostatic conditions remains a much-debated issue. We
describe here, based on an inducible AID fate-mapping mouse model, that systemic
memory B cell subsets, including mainly IgM+ B cells in spleen, together with
IgA+ plasma cells in spleen and bone marrow, are generated in mice in the absence
of deliberate immunization. While the IgA component appears dependent on the gut
flora, IgM memory B cells are still generated in germ-free mice, albeit to a
reduced extent. Clonal relationships and renewal kinetics after anti-CD20
treatment reveal that this long-lasting splenic population is mainly sustained by
output of B cell clones persisting in mucosal germinal centers. IgM-secreting
hybridomas established from splenic IgM memory B cells showed reactivity against
various bacterial isolates and endogenous retroviruses. Ongoing activation of B
cells in gut-associated lymphoid tissues thus generates a diversified systemic
compartment showing long-lasting clonal persistence and protective capacity
against systemic bacterial infections.
PMID- 29959175
TI - Boyd RW, Ellison AM, Horn IB. Police, Equity, and Child Health. Pediatrics.
2016;137(3):e20152711.
PMID- 29959174
TI - Abscess or something worse?
PMID- 29959176
TI - O'Neil J, Hoffman BD; COUNCIL ON INJURY, VIOLENCE, AND POISON PREVENTION. School
Bus Transportation of Children With Special Health Care Needs. Pediatrics.
2018;141(5):e20180513.
PMID- 29959177
TI - Growth Hormone Deficiency Causing Micropenis: Lessons Learned From a Well
Adjusted Adult.
AB - This report of a 46,XY patient born with a micropenis consistent with etiology
from isolated congenital growth hormone deficiency is used to (1) raise the
question regarding what degree testicular testosterone exposure to the central
nervous system during fetal life and early infancy has on the development of male
gender identity, regardless of gender of rearing; (2) suggest the obligatory
nature of timely full disclosure of medical history; (3) emphasize that virtually
all 46,XY infants with functional testes and a micropenis should be initially
boys except some with partial androgen insensitivity syndrome; and (4) highlight
the sustaining value of a positive long-term relationship with a trusted
physician (R.M.B.). When this infant presented, it was commonly considered
inappropriate to gender assign an infant male whose penis was so small that an
adult size was expected to be inadequate, even if the karyotype was 46,XY, and
testes were functional. Concomitantly, female gender assignment was considered
the appropriate decision, believing that parental rearing in the assigned gender
was considered the major factor determining established adult gender identity.
Full disclosure of medical information was considered inappropriate. Progress in
appreciating the complexities of gender identity development, which is not yet
completely understood, and sexuality, coping ability, and outcome data has
resulted in a change of practice in initial gender assignment. A 46,XY individual
with functional testes and verified androgen responsiveness should be assigned
and reared as male, regardless of penis size. Without androgen responsiveness,
the multiple factors must be carefully considered and disclosed.
PMID- 29959178
TI - Case reports on dangerous infectious diseases: a review of patient consent.
AB - Case reports are commonly used to describe new infectious diseases. In the past
20 years, there have been an increasing number of emerging infectious diseases
that could constitute a major threat to global health security (through naturally
occurring pandemics or deliberate release of infectious agents). It is vitally
important that case reports related to infectious diseases are written up
according to the highest possible standards and that guidelines regarding patient
consent to publish are followed. So, do case reports that relate to dangerous
infectious diseases follow guidance related to patient consent? To help find the
answer to this question, I looked at a sample of case reports published on PubMed
between 1 January 2014 and 31 December 2016. I searched for freely available full
text reports of infections that affected humans. The search was conducted for
case reports on infectious diseases that pose the greatest risk to global health
infections that have been classified as Tier 1 agents by the Centers for Disease
Control and Prevention. An assessment was carried out as to whether the
identified case reports satisfied the criteria related to consent as outlined in
the CARE guidelines. In total, 71 case reports were found. These were related to
Ebola, Botulism, Yersinia and Tularaemia. The authors stated that they had
obtained consent to publish in 17 of these case reports. Only a minority of
published case reports on extremely dangerous pathogens contain documented
evidence that consent was obtained from the patient in question. In this sample,
24% of case reports contained such evidence regarding consent.
PMID- 29959179
TI - Significance Testing for Allelic Heterogeneity.
AB - It is useful to detect allelic heterogeneity (AH), i.e., the presence of multiple
causal SNPs in a locus, which, for example, may guide the development of new
methods for fine mapping and determine how to interpret an appearing epistasis.
In contrast to Mendelian traits, the existence and extent of AH for complex
traits had been largely unknown until Hormozdiari et al. proposed a Bayesian
method, called causal variants identification in associated regions (CAVIAR), and
uncovered widespread AH in complex traits. However, there are several limitations
with CAVIAR. First, it assumes a maximum number of causal SNPs in a locus,
typically up to six, to save computing time; this assumption, as will be shown,
may influence the outcome. Second, its computational time can be too demanding to
be feasible since it examines all possible combinations of causal SNPs (under the
assumed upper bound). Finally, it outputs a posterior probability of AH, which
may be difficult to calibrate with a commonly used nominal significance level.
Here, we introduce an intersection-union test (IUT) based on a joint/conditional
regression model with all the SNPs in a locus to infer AH. We also propose two
sequential IUT-based testing procedures to estimate the number of causal SNPs.
Our proposed methods are applicable to not only individual-level genotypic and
phenotypic data, but also genome-wide association study (GWAS) summary
statistics. We provide numerical examples based on both simulated and real data,
including large-scale schizophrenia (SCZ) and high-density lipoprotein (HDL) GWAS
summary data sets, to demonstrate the effectiveness of the new methods. In
particular, for both the SCZ and HDL data, our proposed IUT not only was faster,
but also detected more AH loci than CAVIAR. Our proposed methods are expected to
be useful in further uncovering the extent of AH in complex traits.
PMID- 29959180
TI - Genetics of neuromuscular fetal akinesia in the genomics era.
AB - Fetal hypokinesia or akinesia encompasses a broad spectrum of disorders, united
by impaired movement in utero. Often, the underlying aetiology is genetic in
origin, affecting part of the neuromuscular system. The affordable and high
throughput nature of next-generation DNA sequencing has led to an explosion in
disease gene discovery across rare diseases, including fetal akinesias. A genetic
diagnosis has clinical utility as it may affect management and prognosis and
informs recurrence risk, facilitating family planning decisions. More broadly,
knowledge of disease genes increasingly allows population-based preconception
carrier screening, which has reduced the incidence of recessive diseases in
several populations. Despite gains in knowledge of the genetics of fetal
akinesia, many families lack a genetic diagnosis. In this review, we describe the
developments in Mendelian genetics of neuromuscular fetal akinesia in the
genomics era. We examine genetic diagnoses with neuromuscular causes,
specifically including the lower motor neuron, peripheral nerve, neuromuscular
junction and muscle.
PMID- 29959181
TI - Total/high density lipoprotein cholesterol and cardiovascular disease
(re)hospitalization nadir in type 2 diabetes.
AB - Total cholesterol to HDL cholesterol ratio (TC/HDL) is an important prognostic
factor for CVD. This study used restricted cubic spline modeling to investigate
the dose-response associations between TC/HDL and both CVD hospitalization and
CVD rehospitalization in two independent prospective cohorts. The East
Cambridgeshire and Fenland cohort includes 4,704 patients with T2D from 18
general practices in Cambridgeshire. The Randomized controlled trial of Peer
Support In type 2 Diabetes cohort comprises 1,121 patients with T2D with
posttrial follow-up data. TC/HDL and other demographic and clinical measurements
were measured at baseline. Outcomes were CVD hospitalization over 2 years and CVD
rehospitalization after 90 days of the prior CVD hospitalization. Modeling showed
nonlinear relationships between TC/HDL and risks of CVD hospitalization and
rehospitalization consistently in both cohorts (all P < 0.001 for linear tests).
The lowest risks of CVD hospitalization and rehospitalization were consistently
found for TC/HDL at 2.8 (95% CI: 2.6-3.0) in both cohorts and both overall and by
gender. This is lower than the current lipid control target, 4.0 of TC/HDL.
Reducing the TC/HDL target to 2.8 would include a further 33-44% patients with
TC/HDL in the 2.8-4.0 range. Studies are required to assess the effectiveness and
cost-effectiveness of the earlier introduction of, and more intensive, lipid
lowering treatment needed to achieve this new lower TC/HDL target.
PMID- 29959182
TI - Can we further SPARkle the SPAR model?
PMID- 29959184
TI - Structural insights into lethal contractural syndrome type 3 (LCCS3) caused by a
missense mutation of PIP5Kgamma.
AB - Signaling molecule phosphatidylinositol 4,5-bisphosphate is produced primarily by
phosphatidylinositol 4-phosphate 5-kinase (PIP5K). PIP5K is essential for the
development of the human neuronal system, which has been exemplified by a
recessive genetic disorder, lethal congenital contractural syndrome type 3,
caused by a single aspartate-to-asparagine mutation in the kinase domain of
PIP5Kgamma. So far, the exact role of this aspartate residue has yet to be
elucidated. In this work, we conducted structural, functional and computational
studies on a zebrafish PIP5Kalpha variant with a mutation at the same site.
Compared with the structure of the wild-type (WT) protein in the ATP-bound state,
the ATP-associating glycine-rich loop of the mutant protein was severely
disordered and the temperature factor of ATP was significantly higher. Both
observations suggest a greater degree of disorder of the bound ATP, whereas
neither the structure of the catalytic site nor the Km toward ATP was
substantially affected by the mutation. Microsecond molecular dynamics simulation
revealed that negative charge elimination caused by the mutation destabilized the
involved hydrogen bonds and affected key electrostatic interactions in the close
proximity of ATP. Taken together, our data indicated that the disease-related
aspartate residue is a key node in the interaction network crucial for effective
ATP binding. This work provides a paradigm of how a subtle but critical
structural perturbation caused by a single mutation at the ATP-binding site
abolishes the kinase activity, emphasizing that stabilizing substrate in a
productive conformational state is crucial for catalysis.
PMID- 29959183
TI - Non-classical monocytes as mediators of tissue destruction in arthritis.
AB - OBJECTIVES: Bone destruction in rheumatoid arthritis is mediated by osteoclasts
(OC), which are derived from precursor cells of the myeloid lineage. The role of
the two monocyte subsets, classical monocytes (expressing CD115, Ly6C and CCR2)
and non-classical monocytes (which are CD115 positive, but low in Ly6C and CCR2),
in serving as precursors for OC in arthritis is still elusive. METHODS: We
investigated CCR2-/- mice, which lack circulating classical monocytes, crossed
into hTNFtg mice for the extent of joint damage. We analysed monocyte subsets in
hTNFtg and K/BxN serum transfer arthritis by flow cytometry. We sorted monocyte
subsets and analysed their potential to differentiate into OC and their
transcriptional response in response to RANKL by RNA sequencing. With these data,
we performed a gene ontology enrichment analysis and gene set enrichment
analysis. RESULTS: We show that in hTNFtg arthritis local bone erosion and OC
generation are even enhanced in the absence of CCR2. We further show the numbers
of non-classical monocytes in blood are elevated and are significantly correlated
with histological signs of joint destruction. Sorted non-classical monocytes
display an increased capacity to differentiate into OCs. This is associated with
an increased expression of signal transduction components of RANK, most
importantly TRAF6, leading to an increased responsiveness to RANKL. CONCLUSION:
Therefore, non-classical monocytes are pivotal cells in arthritis tissue damage
and a possible target for therapeutically intervention for the prevention of
inflammatory joint damage.
PMID- 29959185
TI - Structure, interactions and action of Mycobacterium tuberculosis 3
hydroxyisobutyric acid dehydrogenase.
AB - Biochemical and crystallographic studies on Mycobacterium tuberculosis 3
hydroxyisobutyric acid dehydrogenase (MtHIBADH), a member of the 3-hydroxyacid
dehydrogenase superfamily, have been carried out. Gel filtration and blue native
PAGE of MtHIBADH show that the enzyme is a dimer. The enzyme preferentially uses
NAD+ as the cofactor and is specific to S-hydroxyisobutyric acid (HIBA). It can
also use R-HIBA, l-serine and 3-hydroxypropanoic acid (3-HP) as substrates, but
with much less efficiency. The pH optimum for activity is ~11. Structures of the
native enzyme, the holoenzyme, binary complexes with NAD+, S-HIBA, R-HIBA, l
serine and 3-HP and ternary complexes involving the substrates and NAD+ have been
determined. None of the already known structures of HIBADH contain a substrate
molecule at the binding site. The structures reported here provide for the first
time, among other things, a clear indication of the location and interactions of
the substrates at the active site. They also define the entrance of the
substrates to the active site region. The structures provide information on the
role of specific residues at the active site and the entrance. The results
obtained from crystal structures are consistent with solution studies including
mutational analysis. They lead to the proposal of a plausible mechanism of the
action of the enzyme.
PMID- 29959186
TI - The renal protect function of erythropoietin after release of bilateral ureteral
obstruction in a rat model.
AB - Congenital urinary tract obstruction is one of the most frequent malformations in
fetuses or neonates, which usually causes profound impairment of renal function
including reductions in both glomerular filtration rate (GFR) and tubular
handling of water and solutes. Although obstruction can be released by surgical
operation, the child will suffer from diuresis for sometime. It has been reported
that erythropoietin (EPO) could prevent the down-regulation of aquaporin-2 (AQP2)
and urinary-concentrating defects induced by renal ischemia/reperfusion (I/R)
injury. However, whether EPO could promote the recovery of renal function and
AQP2 expression after releasing of ureteral obstruction has not been reported
yet. The purposes of the present study were to investigate the effects of EPO on
renal function and AQP2 expression after release of bilateral ureteral
obstruction (BUO-R) in rats. The results showed that EPO could promote
interleukin (IL) 10 (IL-10) expression; inhibit tumor necrosis factor-alpha (TNF
alpha), IL-6, and inducible nitric oxide synthase (iNOS) expressions; reduce the
fractional excretion of sodium (FENa) and plasma creatinine (CREA) and urea; and
promote the recovery of water and salt handling and AQP2 expression in BUO-R
rats, especially in the high dose of EPO-treated group rats. In conclusion, EPO
could promote the recovery of renal function and AQP2 expression in BUO-R rats,
which may partially associate with its anti-inflammation effect.
PMID- 29959187
TI - Psychological perspective on compassion in modern healthcare settings.
AB - Compassionate care is a foundation of the National Health Service (NHS). However,
several high-profile inquiries into healthcare failures in the NHS suggest
compassion is often absent in our hospitals. Ensuing policies mandate healthcare
professionals to 'show more compassion' but, as the psychological evidence-base
indicates, this instruction neglects the complexity of this social emotion. This
paper applies the psychological research on compassion to modern healthcare
settings with the aim of creating a better understanding of the pathways leading
to uncompassionate care. A review of the empirical evidence suggests a range of
psychological factors modulate compassion. In particular, the psychological
literature indicates the human compassion system is adaptive, highly attuned to
its environment. As such, a healthcare professional's ability to experience and
display compassionate behaviour will be, in part, determined by the environment
in which they practise; that is, aspects of the organisational environment will
either facilitate or inhibit compassion. This paper argues that the typical
organisational set-up of a modern healthcare setting seriously undermines
compassionate care. Organisational features frequently associated with
uncompassionate care include the understaffing of hospital wards, excessive
working shift patterns and the dogged focus on achieving service efficiencies
each has been identified as contributing to the alarming breakdown of
compassionate care at the centre of several healthcare failings. Policies
focusing on culture change in the NHS neglect the growing psychological evidence
base on compassion, but by applying a psychological understanding of compassion
to healthcare settings, we can begin to adequately understand and address the
real causes of uncompassionate care.
PMID- 29959189
TI - SRC-3 is involved in maintaining hematopoietic stem cell quiescence by regulation
of mitochondrial metabolism in mice.
AB - Quiescence maintenance is an important property of hematopoietic stem cells
(HSCs), whereas the regulatory factors and underlying mechanisms involved in HSC
quiescence maintenance are not fully uncovered. Here, we show that steroid
receptor coactivator 3 (SRC-3) is highly expressed in HSCs, and SRC-3-deficient
HSCs are less quiescent and more proliferative, resulting in increased
sensitivity to chemotherapy and irradiation. Moreover, the long-term
reconstituting ability of HSCs is markedly impaired in the absence of SRC-3, and
SRC-3 knockout (SRC-3-/-) mice exhibit a significant disruption of hematopoietic
stem and progenitor cell homeostasis. Further investigations show that SRC-3
deficiency leads to enhanced mitochondrial metabolism, accompanied by
overproduction of reactive oxygen species (ROS) in HSCs. Notably, the downstream
target genes of peroxisome proliferator-activated receptor-coactivators 1alpha
(PGC-1alpha) involved in the regulation of mitochondrial metabolism are
significantly upregulated in SRC-3-deficient HSCs. Meanwhile, a significant
decrease in the expression of histone acetyltransferase GCN5 accompanied by
downregulation of PGC-1alpha acetylation is observed in SRC-3-null HSCs.
Conversely, overexpression of GCN5 can inhibit SRC-3 deficiency-induced
mitochondrial metabolism enhancement and ROS overproduction, thereby evidently
rescuing the impairment of HSCs in SRC-3-/- mice. Collectively, our findings
demonstrate that SRC-3 plays an important role in HSC quiescence maintenance by
regulating mitochondrial metabolism.
PMID- 29959190
TI - Noncanonical Translation Initiation in Eukaryotes.
AB - The vast majority of eukaryotic messenger RNAs (mRNAs) initiate translation
through a canonical, cap-dependent mechanism requiring a free 5' end and 5' cap
and several initiation factors to form a translationally active ribosome.
Stresses such as hypoxia, apoptosis, starvation, and viral infection down
regulate cap-dependent translation during which alternative mechanisms of
translation initiation prevail to express proteins required to cope with the
stress, or to produce viral proteins. The diversity of noncanonical initiation
mechanisms encompasses a broad range of strategies and cellular cofactors.
Herein, we provide an overview and, whenever possible, a mechanistic
understanding of the various noncanonical mechanisms of initiation used by cells
and viruses. Despite many unanswered questions, recent advances have propelled
our understanding of the scope, diversity, and mechanisms of alternative
initiation.
PMID- 29959188
TI - Proteomic Analysis of Hippocampus in a Mouse Model of Depression Reveals
Neuroprotective Function of Ubiquitin C-terminal Hydrolase L1 (UCH-L1) via Stress
induced Cysteine Oxidative Modifications.
AB - Chronic physical restraint stress increases oxidative stress in the brain, and
dysregulation of oxidative stress can be one of the causes of major depressive
disorder. To understand the underlying mechanisms, we undertook a systematic
proteomic analysis of hippocampus in a chronic restraint stress mouse model of
depression. Combining two-dimensional gel electrophoresis (2D-PAGE) for protein
separation with nanoUPLC-ESI-q-TOF tandem mass spectrometry, we identified sixty
three protein spots that changed in the hippocampus of mice subjected to chronic
restraint stress. We identified and classified the proteins that changed after
chronic stress, into three groups respectively functioning in neural plasticity,
metabolic processes and protein aggregation. Of these, 5 proteins including
ubiquitin C-terminal hydrolase L1 (UCH-L1), dihydropyrimidinase-related protein 2
(DPYL2), haloacid dehalogenase-like hydrolase domain-containing protein 2
(HDHD2), actin-related protein 2/3 complex subunit 5 (ARPC5) and peroxiredoxin-2
(PRDX2), showed pI shifts attributable to post-translational modifications.
Further analysis indicated that UCH-L1 underwent differential oxidations of 2
cysteine residues following chronic stress. We investigated whether the oxidized
form of UCH-L1 plays a role in stressed hippocampus, by comparing the effects of
UCH-L1 and its Cys mutants on hippocampal cell line HT-22 in response to
oxidative stress. This study demonstrated that UCH-L1 wild-type and cysteine to
aspartic acid mutants, but not its cysteine to serine mutants, afforded
neuroprotective effects against oxidative stress; there were no discernible
differences between wild-type UCH-L1 and its mutants in the absence of oxidative
stress. These findings suggest that cysteine oxidative modifications of UCH-L1 in
the hippocampus play key roles in neuroprotection against oxidative stress caused
in major depressive disorder.
PMID- 29959191
TI - Phosphorylation and Signal Transduction Pathways in Translational Control.
AB - Protein synthesis, including the translation of specific messenger RNAs (mRNAs),
is regulated by extracellular stimuli such as hormones and by the levels of
certain nutrients within cells. This control involves several well-understood
signaling pathways and protein kinases, which regulate the phosphorylation of
proteins that control the translational machinery. These pathways include the
mechanistic target of rapamycin complex 1 (mTORC1), its downstream effectors, and
the mitogen-activated protein (MAP) kinase (extracellular ligand-regulated kinase
[ERK]) signaling pathway. This review describes the regulatory mechanisms that
control translation initiation and elongation factors, in particular the effects
of phosphorylation on their interactions or activities. It also discusses current
knowledge concerning the impact of these control systems on the translation of
specific mRNAs or subsets of mRNAs, both in physiological processes and in
diseases such as cancer.
PMID- 29959192
TI - Toward a Kinetic Understanding of Eukaryotic Translation.
AB - The eukaryotic translation pathway has been studied for more than four decades,
but the molecular mechanisms that regulate each stage of the pathway are not
completely defined. This is in part because we have very little understanding of
the kinetic framework for the assembly and disassembly of pathway intermediates.
Steps of the pathway are thought to occur in the subsecond to second time frame,
but most assays to monitor these events require minutes to hours to complete.
Understanding translational control in sufficient detail will therefore require
the development of assays that can precisely monitor the kinetics of the
translation pathway in real time. Here, we describe the translation pathway from
the perspective of its kinetic parameters, discuss advances that are helping us
move toward the goal of a rigorous kinetic understanding, and highlight some of
the challenges that remain.
PMID- 29959193
TI - Translational Control in Cancer.
AB - The translation of messenger RNAs (mRNAs) into proteins is a key event in the
regulation of gene expression. This is especially true in the cancer setting, as
many oncogenes and transforming events are regulated at this level. Cancer
promoting factors that are translationally regulated include cyclins,
antiapoptotic factors, proangiogenic factors, regulators of cell metabolism,
prometastatic factors, immune modulators, and proteins involved in DNA repair.
This review discusses the diverse means by which cancer cells deregulate and
reprogram translation, and the resulting oncogenic impacts, providing insights
into the complexity of translational control in cancer and its targeting for
cancer therapy.
PMID- 29959194
TI - Mechanistic Insights into MicroRNA-Mediated Gene Silencing.
AB - MicroRNAs (miRNAs) posttranscriptionally regulate gene expression by repressing
protein synthesis and exert a broad influence over development, physiology,
adaptation, and disease. Over the past two decades, great strides have been made
toward elucidating how miRNAs go about shutting down messenger RNA (mRNA)
translation and promoting mRNA decay.
PMID- 29959195
TI - Principles of Translational Control.
AB - Protein synthesis involves a complex machinery comprising numerous proteins and
RNAs joined by noncovalent interactions. Its function is to link long chains of
amino acids into proteins with precise sequences as encoded by the genome.
Regulation of protein synthesis, called translational control, occurs both at a
global level and at specific messenger RNAs (mRNAs). To understand how
translation is regulated, knowledge of the molecular structures and kinetic
interactions of its components is needed. This review focuses on the targets of
translational control and the mechanisms employed.
PMID- 29959196
TI - Nephrotoxicity of Cancer Immunotherapies: Past, Present and Future.
AB - Nephrotoxicity from cancer therapies is common and increasingly encountered in
clinical practice, such that the subfield of "onco-nephrology" has emerged.
Conventional chemotherapeutic drugs and novel agents targeting specific
genes/proteins are effective cancer therapies but suffer from a number of adverse
kidney effects. An effective avenue of cancer treatment is immunotherapy, which
uses drugs that augment immune system-mediated recognition and targeting of tumor
cells. As such, leveraging the immune system to target malignant cells represents
an important modality in eradicating cancer. IFN and high-dose IL-2 are older
immunotherapies used in clinical practice to treat various malignancies, whereas
new cancer immunotherapies have emerged over the past decade that offer even more
effective treatment options. The immune checkpoint inhibitors are an exciting
addition to the cancer immunotherapy armamentarium. Chimeric antigen receptor T
cells are also a new immunotherapy used to treat various hematologic
malignancies. However, as with the conventional and targeted cancer agents, the
immunotherapies are also associated with immune-related adverse effects, which
includes nephrotoxicity.
PMID- 29959199
TI - Targeting Notch1 and IKKalpha Enhanced NF-kappaB Activation in CD133+ Skin Cancer
Stem Cells.
AB - Cancer stem-like cells are hypothesized to be the major tumor-initiating cell
population of human cutaneous squamous cell carcinoma (cSCC), but the landscape
of molecular alterations underpinning their signaling and cellular phenotypes as
drug targets remains undefined. In this study, we developed an experimental
pipeline to isolate a highly enriched CD133+CD31-CD45-CD61-CD24- (CD133+) cell
population from primary cSCC specimens by flow cytometry. The CD133+ cells show
enhanced stem-like phenotypes, which were verified by spheroid and colony
formation in vitro and tumor generation in vivo Gene expression profiling of
CD133+/- cells was compared and validated, and differentially expressed gene
signatures and top pathways were identified. CD133+ cells expressed a repertoire
of stemness and cancer-related genes, including NOTCH and NOTCH1-mediated NF
kappaB pathway signaling. Other cancer-related genes from WNT, growth factor
receptors, PI3K/mTOR, STAT pathways, and chromatin modifiers were also
identified. Pharmacologic and genetic targeting of NOTCH1, IKKalpha, RELA, and
RELB modulated NF-kappaB transactivation, the CD133+ population, and cellular and
stemness phenotypes. Immunofluorescent staining confirmed colocalization of
CD133+ and IKKalpha expression in SCC tumor specimens. Our functional, genetic,
and pharmacologic studies uncovered a novel linkage between NOTCH1, IKKalpha, and
NF-kappaB pathway activation in maintaining the CD133+ stem SCC phenotypes.
Studies investigating markers of activation and modulators of NOTCH, IKK/NF
kappaB, and other pathways regulating these cancer stem gene signatures could
further accelerate the development of effective therapeutic strategies to treat
cSCC recurrence and metastasis. Mol Cancer Ther; 17(9); 2034-48. (c)2018 AACR.
PMID- 29959198
TI - Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X
linked Alport Syndrome.
AB - BACKGROUND: X-linked Alport syndrome (XLAS) is a progressive hereditary
nephropathy caused by mutations in the COL4A5 gene. Genotype-phenotype
correlation in male XLAS is relatively well established; relative to truncating
mutations, nontruncating mutations exhibit milder phenotypes. However, transcript
comparison between XLAS cases with splicing abnormalities that result in a
premature stop codon and those with nontruncating splicing abnormalities has not
been reported, mainly because transcript analysis is not routinely conducted in
patients with XLAS. METHODS: We examined transcript expression for all patients
with suspected splicing abnormalities who were treated at one hospital between
January of 2006 and July of 2017. Additionally, we recruited 46 males from 29
families with splicing abnormalities to examine genotype-phenotype correlation in
patients with truncating (n=21, from 14 families) and nontruncating (n=25, from
15 families) mutations at the transcript level. RESULTS: We detected 41 XLAS
families with abnormal splicing patterns and described novel XLAS atypical
splicing patterns (n=14) other than exon skipping caused by point mutations in
the splice consensus sequence. The median age for developing ESRD was 20 years
(95% confidence interval, 14 to 23 years) among patients with truncating
mutations and 29 years (95% confidence interval, 25 to 40 years) among patients
with nontruncating mutations (P=0.001). CONCLUSIONS: We report unpredictable
atypical splicing in the COL4A5 gene in male patients with XLAS and reveal that
renal prognosis differs significantly for patients with truncating versus
nontruncating splicing abnormalities. Our results suggest that splicing
modulation should be explored as a therapy for XLAS with truncating mutations.
PMID- 29959197
TI - GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome.
AB - BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of
CKD. The discovery of monogenic causes of SRNS has revealed specific pathogenetic
pathways, but these monogenic causes do not explain all cases of SRNS. METHODS:
To identify novel monogenic causes of SRNS, we screened 665 patients by whole
exome sequencing. We then evaluated the in vitro functional significance of two
genes and the mutations therein that we discovered through this sequencing and
conducted complementary studies in podocyte-like Drosophila nephrocytes. RESULTS:
We identified conserved, homozygous missense mutations of GAPVD1 in two families
with early-onset NS and a homozygous missense mutation of ANKFY1 in two siblings
with SRNS. GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5.
Coimmunoprecipitation assays indicated interaction between GAPVD1 and ANKFY1
proteins, which also colocalized when expressed in HEK293T cells. Silencing
either protein diminished the podocyte migration rate. Compared with wild-type
GAPVD1 and ANKFY1, the mutated proteins produced upon ectopic expression of
GAPVD1 or ANKFY1 bearing the patient-derived mutations exhibited altered binding
affinity for active RAB5 and reduced ability to rescue the knockout-induced
defect in podocyte migration. Coimmunoprecipitation assays further demonstrated a
physical interaction between nephrin and GAPVD1, and immunofluorescence revealed
partial colocalization of these proteins in rat glomeruli. The patient-derived
GAPVD1 mutations reduced nephrin-GAPVD1 binding affinity. In Drosophila,
silencing Gapvd1 impaired endocytosis and caused mistrafficking of the nephrin
ortholog. CONCLUSIONS: Mutations in GAPVD1 and probably in ANKFY1 are novel
monogenic causes of NS. The discovery of these genes implicates RAB5 regulation
in the pathogenesis of human NS.
PMID- 29959200
TI - Arsenic Trioxide and Sorafenib Induce Synthetic Lethality of FLT3-ITD Acute
Myeloid Leukemia Cells.
AB - Acute myeloid leukemia (AML) with Fms-related tyrosine kinase 3 internal tandem
duplication (FLT3-ITD) mutation is notoriously hard to treat. We identified two
drugs that together form an effective combination therapy against FLT3-ITD AML.
One of the drugs, Sorafenib, an inhibitor of FLT3-ITD and other kinase activity,
produces an impressive but short-lived remission in FLT3-ITD AML patients. The
second, arsenic trioxide (ATO), at therapeutically achievable concentrations,
reduces the level of FLT3-ITD and Mcl-1 proteins, and induces apoptosis in
leukemic cell lines and in primary cells expressing FLT3-ITD. We linked this
relative sensitivity to ATO to low levels of reduced glutathione. While producing
proapoptotic effects, ATO treatment also has an unwanted effect whereby it causes
the accumulation of the phosphorylated (inactive) form of glycogen synthase
kinase 3beta (GSK3beta), a kinase necessary for apoptosis. When ATO is combined
with Sorafenib, GSK3beta is activated, Mcl-1 is further reduced, and proapoptotic
proteins Bak and Bax are activated. Mice xenografted with FLT3-ITD MOLM13 cell
line treated with the Sorafenib/ATO combination have significantly improved
survival. This combination has potential to improve the therapeutic outcome of
FLT3-ITD-targeted therapy of AML patients. Mol Cancer Ther; 17(9); 1871-80.
(c)2018 AACR.
PMID- 29959201
TI - A Quinoline-Based DNA Methyltransferase Inhibitor as a Possible Adjuvant in
Osteosarcoma Therapy.
AB - The identification of new therapeutic strategies against osteosarcoma, the most
common primary bone tumor, continues to be a primary goal to improve the outcomes
of patients refractory to conventional chemotherapy. Osteosarcoma originates from
the transformation of mesenchymal stem cells (MSC) and/or osteoblast progenitors,
and the loss of differentiation is a common biological osteosarcoma feature,
which has strong significance in predicting tumor aggressiveness. Thus, restoring
differentiation through epigenetic reprogramming is potentially exploitable for
therapeutic benefits. Here, we demonstrated that the novel nonnucleoside DNMT
inhibitor (DNMTi) MC3343 affected tumor proliferation by blocking osteosarcoma
cells in G1 or G2-M phases and induced osteoblastic differentiation through the
specific reexpression of genes regulating this physiologic process. Although
MC3343 has a similar antiproliferative effect as 5azadC, the conventional FDA
approved nucleoside inhibitor of DNA methylation, its effects on cell
differentiation are distinct. Induction of the mature osteoblast phenotype
coupled with a sustained cytostatic response was also confirmed in vivo when
MC3343 was used against a patient-derived xenograft (PDX). In addition, MC3343
displayed synergistic effects with doxorubicin and cisplatin (CDDP), two major
chemotherapeutic agents used to treat osteosarcoma. Specifically, MC3343
increased stable doxorubicin bonds to DNA, and combined treatment resulted in
sustained DNA damage and increased cell death. Overall, this nonnucleoside DNMTi
is an effective novel agent and is thus a potential therapeutic option for
patients with osteosarcoma who respond poorly to preadjuvant chemotherapy. Mol
Cancer Ther; 17(9); 1881-92. (c)2018 AACR.
PMID- 29959202
TI - Dual Targeting of ERBB2/ERBB3 for the Treatment of SLC3A2-NRG1-Mediated Lung
Cancer.
AB - We characterized the SLC3A2-NRG1 fusion gene in non-small cell lung cancer
(NSCLC) and established an effective therapy for patients with SLC3A2-NRG1 fusion
positive cancer. The SLC3A2-NRG1 fusion product was composed of the SLC3A2
transmembrane domain and the EGF-like domain of the neuregulin 1 (NRG1) protein.
The NRG1 family is classified as a ligand of the ERBB family. We identified ERBB3
and ERBB4 in the ERBB family as binding partners of the SLC3A2-NRG1 fusion
protein via ligand and receptor binding assays. We confirmed that SLC3A2-NRG1
increased formation of a heterocomplex of ERBB3 with ERBB2. Activation of the
ERBB2-ERBB3 heterocomplex by SLC3A2-NRG1 increased colony formation and tumor
growth through PI3K-AKT and MAP kinase. The specific siRNAs for ERBB2 and ERBB3,
pertuzumab, lumretuzumab, and afatinib all decreased ERBB2-ERBB3 heterocomplex
formation, phosphorylation of each protein, and their downstream signaling. In
addition, single treatment with pertuzumab, lumretuzumab, or afatinib decreased
tumor volume and weight, whereas combination treatment with these drugs and taxol
enhanced generation of cleaved caspase 3, PARP, and TUNEL-positive cells compared
with each single treatment. Thus, the SLC3A2-NRG1 fusion gene plays an important
role in lung cancer cell proliferation and tumor growth by promoting generation
of the ERBB2-ERBB3 heterocomplex, its phosphorylation, and activation of the
PI3K/ERK/mTOR signaling pathway. Inhibition of either ERBB2 or ERBB3 alone did
not completely shut down downstream signaling of ERBB2 and ERBB3; however,
inhibition of both ERBB2 and ERBB3 blocked downstream signaling activated by
SLC3A2-NRG1 fusion. ERBB2 and ERBB3 might be promising targets for treatment of
SLC3A2-NRG1-positive tumors. Mol Cancer Ther; 17(9); 2024-33. (c)2018 AACR.
PMID- 29959203
TI - Genetic dissection of neuropeptide cell biology at high and low activity in a
defined sensory neuron.
AB - Neuropeptides are ubiquitous modulators of behavior and physiology. They are
packaged in specialized secretory organelles called dense core vesicles (DCVs)
that are released upon neural stimulation. Unlike synaptic vesicles, which can be
recycled and refilled close to release sites, DCVs must be replenished by de novo
synthesis in the cell body. Here, we dissect DCV cell biology in vivo in a
Caenorhabditis elegans sensory neuron whose tonic activity we can control using a
natural stimulus. We express fluorescently tagged neuropeptides in the neuron and
define parameters that describe their subcellular distribution. We measure these
parameters at high and low neural activity in 187 mutants defective in proteins
implicated in membrane traffic, neuroendocrine secretion, and neuronal or
synaptic activity. Using unsupervised hierarchical clustering methods, we analyze
these data and identify 62 groups of genes with similar mutant phenotypes. We
explore the function of a subset of these groups. We recapitulate many previous
findings, validating our paradigm. We uncover a large battery of proteins
involved in recycling DCV membrane proteins, something hitherto poorly explored.
We show that the unfolded protein response promotes DCV production, which may
contribute to intertissue communication of stress. We also find evidence that
different mechanisms of priming and exocytosis may operate at high and low neural
activity. Our work provides a defined framework to study DCV biology at different
neural activity levels.
PMID- 29959204
TI - Extreme stability in de novo-designed repeat arrays is determined by unusually
stable short-range interactions.
AB - Designed helical repeats (DHRs) are modular helix-loop-helix-loop protein
structures that are tandemly repeated to form a superhelical array. Structures
combining tandem DHRs demonstrate a wide range of molecular geometries, many of
which are not observed in nature. Understanding cooperativity of DHR proteins
provides insight into the molecular origins of Rosetta-based protein design
hyperstability and facilitates comparison of energy distributions in artificial
and naturally occurring protein folds. Here, we use a nearest-neighbor Ising
model to quantify the intrinsic and interfacial free energies of four different
DHRs. We measure the folding free energies of constructs with varying numbers of
internal and terminal capping repeats for four different DHR folds, using
guanidine-HCl and glycerol as destabilizing and solubilizing cosolvents. One
dimensional Ising analysis of these series reveals that, although interrepeat
coupling energies are within the range seen for naturally occurring repeat
proteins, the individual repeats of DHR proteins are intrinsically stable. This
favorable intrinsic stability, which has not been observed for naturally
occurring repeat proteins, adds to stabilizing interfaces, resulting in
extraordinarily high stability. Stable repeats also impart a downhill shape to
the energy landscape for DHR folding. These intrinsic stability differences
suggest that part of the success of Rosetta-based design results from capturing
favorable local interactions.
PMID- 29959205
TI - How functional traits influence plant growth and shade tolerance across the life
cycle.
AB - Plant species differ in many functional traits that drive differences in rates of
photosynthesis, biomass allocation, and tissue turnover. However, it remains
unclear how-and even if-such traits influence whole-plant growth, with the simple
linear relationships predicted by existing theory often lacking empirical
support. Here, we present a theoretical framework for understanding the effect of
diverse functional traits on plant growth and shade tolerance by extending a
widely used model, linking growth rate in seedlings with a single leaf trait, to
explicitly include influences of size, light environment, and five prominent
traits: seed mass, height at maturation, leaf mass per unit leaf area, leaf
nitrogen per unit leaf area, and wood density. Based on biomass growth and
allocation, this framework explains why the influence of traits on growth rate
and shade tolerance often varies with plant size and why the impact of size on
growth varies among traits. Specifically, we demonstrate why for height growth
the influence of: (i) leaf mass per unit leaf area is strong in small plants but
weakens with size; (ii) leaf nitrogen per unit leaf area does not change with
size; (iii) wood density is present across sizes; (iv) height at maturation
strengthens with size; and (v) seed mass decreases with size. Moreover, we show
how traits moderate plant responses to light environment and also determine shade
tolerance, supporting diverse empirical results.
PMID- 29959206
TI - Distribution shapes govern the discovery of predictive models for gene
regulation.
AB - Despite substantial experimental and computational efforts, mechanistic modeling
remains more predictive in engineering than in systems biology. The reason for
this discrepancy is not fully understood. One might argue that the randomness and
complexity of biological systems are the main barriers to predictive
understanding, but these issues are not unique to biology. Instead, we
hypothesize that the specific shapes of rare single-molecule event distributions
produce substantial yet overlooked challenges for biological models. We
demonstrate why modern statistical tools to disentangle complexity and
stochasticity, which assume normally distributed fluctuations or enormous
datasets, do not apply to the discrete, positive, and nonsymmetric distributions
that characterize mRNA fluctuations in single cells. As an example, we integrate
single-molecule measurements and advanced computational analyses to explore
mitogen-activated protein kinase induction of multiple stress response genes.
Through systematic analyses of different metrics to compare the same model to the
same data, we elucidate why standard modeling approaches yield nonpredictive
models for single-cell gene regulation. We further explain how advanced tools
recover precise, reproducible, and predictive understanding of transcription
regulation mechanisms, including gene activation, polymerase initiation,
elongation, mRNA accumulation, spatial transport, and decay.
PMID- 29959207
TI - S4-S5 linker movement during activation and inactivation in voltage-gated K+
channels.
AB - The S4-S5 linker physically links voltage sensor and pore domain in voltage-gated
ion channels and is essential for electromechanical coupling between both
domains. Little dynamic information is available on the movement of the cytosolic
S4-S5 linker due to lack of a direct electrical or optical readout. To understand
the movements of the gating machinery during activation and inactivation, we
incorporated fluorescent unnatural amino acids at four positions along the linker
of the Shaker KV channel. Using two-color voltage-clamp fluorometry, we compared
S4-S5 linker movements with charge displacement, S4 movement, and pore opening.
We found that the proximal S4-S5 linker moves with the S4 helix throughout the
gating process, whereas the distal portion undergoes a separate motion related to
late gating transitions. Both pore and S4-S5 linker undergo rearrangements during
C-type inactivation. In presence of accelerated C-type inactivation, the
energetic coupling between movement of the distal S4-S5 linker and pore opening
disappears.
PMID- 29959208
TI - Relational mobility predicts social behaviors in 39 countries and is tied to
historical farming and threat.
AB - Biologists and social scientists have long tried to understand why some societies
have more fluid and open interpersonal relationships and how those differences
influence culture. This study measures relational mobility, a socioecological
variable quantifying voluntary (high relational mobility) vs. fixed (low
relational mobility) interpersonal relationships. We measure relational mobility
in 39 societies and test whether it predicts social behavior. People in societies
with higher relational mobility report more proactive interpersonal behaviors
(e.g., self-disclosure and social support) and psychological tendencies that help
them build and retain relationships (e.g., general trust, intimacy, self-esteem).
Finally, we explore ecological factors that could explain relational mobility
differences across societies. Relational mobility was lower in societies that
practiced settled, interdependent subsistence styles, such as rice farming, and
in societies that had stronger ecological and historical threats.
PMID- 29959209
TI - Eye movements support the link between conscious memory and medial temporal lobe
function.
AB - When individuals select the recently studied (and familiar) item in a multiple
choice memory test, they direct a greater proportion of viewing time toward the
to-be-selected item when their choice is correct than when their choice is
incorrect. Thus, for both correct and incorrect choices, individuals indicate
that the chosen item is old, but viewing time nevertheless distinguishes between
old and new items. What kind of memory supports this preferential viewing effect?
We recorded eye movements while participants made three-alternative, forced
choice recognition memory judgments for scenes. In experiment 1 (n = 30), the
magnitude of the preferential viewing effect was strongly correlated with
measures of conscious, declarative memory: recognition accuracy as well as the
difference in confidence ratings and in response times for correct and incorrect
choices. In four analyses that minimized the contribution of declarative memory
in order to detect a possible contribution from other processes, the preferential
viewing effect was absent. In experiment 2, five memory-impaired patients with
medial temporal lobe lesions exhibited a diminished preferential viewing effect.
These patients also exhibited poor recognition accuracy and reduced differences
in confidence ratings and response times for correct and incorrect choices. We
propose that the preferential viewing effect is a phenomenon of conscious,
declarative memory and is dependent on the medial temporal lobe. The findings
support the link between medial temporal lobe function and declarative memory.
When the effects of experience depend on the medial temporal lobe, the effects
reflect conscious memory.
PMID- 29959211
TI - The Current State of Radiopharmaceutical Therapy.
PMID- 29959212
TI - Metabolic Active Tumor Volume and Total Lesion Glycolysis by 18F-FDG PET/CT
Validated as Prognostic Imaging Biomarkers in Chemorefractory Metastatic
Colorectal Cancer.
AB - This study aimed to validate the prognostic value of baseline whole-body
metabolic active tumor volume (WB-MATV) and total lesion glycolysis (WB-TLG)
measured with [18F]fluorodeoxyglucose positron emission tomography-computed
tomography (18F-FDG PET/CT) in a large cohort of chemorefractory metastatic
colorectal cancer (mCRC) patients treated with multikinase inhibitors (MKI). The
secondary objective of this study was to compare WB-MATV and WB-TLG respective
prognostic values to commonly used clinical prognostic factors. Methods: Out of
238 patients pooled from two successive prospective multicenter trials
investigating MKI in chemorefractory mCRC, 224 were considered suitable for
analysis. The patients were retrospectively randomly assigned to a development
set (n = 155 patients) and a validation set (n = 69 patients). WB-MATV and WB-TLG
optimal cutoffs for prediction of overall survival (OS) were determined by Contal
and O'Quigley's method. Univariate analyses were performed to assess the
prognostic values of WB-MATV and WB-TLG. Multivariate analyses were performed for
WB-MATV and WB-TLG along with clinical factors to identify the independent
prognostic factors of OS. The prognostic weight for each parameter was obtained
from the Cox's model. Results: WB-MATV and WB-TLG optimal cutoffs for OS
prediction were 100 cm3 and 500 g, respectively. Univariate analyses showed that
WB-MATV and WB-TLG parameters were strongly related to outcome in both the
development and validation sets. In the validation set, the median OS was 5.2
months vs 12.8 months for high vs low WB-MATV (HR: 3.12, P < 0.001), and 4.7
months vs 13.9 months for high vs low WB-TLG (HR: 3.67, P < 0.001). The
multivariate analyses identified that both high WB-MATV and WB-TLG were
independent negative prognostic parameters for OS, with the highest prognostic
weight among the well-known clinical prognostic factors (HR: 2.46 and 2.23,
respectively, P < 0.001). Conclusion: Baseline WB-MATV and WB-TLG parameters were
validated as strong prognosticators of outcome in a large cohort of
chemorefractory mCRC patients treated with MKI. These parameters were identified
as independent prognostic imaging biomarkers with the highest prognostic values
among the commonly used clinical factors. These biomarkers should therefore be
used to support the optimal therapeutic strategy.
PMID- 29959210
TI - External light activates hair follicle stem cells through eyes via an ipRGC-SCN
sympathetic neural pathway.
AB - Changes in external light patterns can alter cell activities in peripheral
tissues through slow entrainment of the central clock in suprachiasmatic nucleus
(SCN). It remains unclear whether cells in otherwise photo-insensitive tissues
can achieve rapid responses to changes in external light. Here we show that light
stimulation of animals' eyes results in rapid activation of hair follicle stem
cells with prominent hair regeneration. Mechanistically, light signals are
interpreted by M1-type intrinsically photosensitive retinal ganglion cells
(ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent
sympathetic nerves are immediately activated. Increased norepinephrine release in
skin promotes hedgehog signaling to activate hair follicle stem cells. Thus,
external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic
nervous system circuit. Since activation of sympathetic nerves is not limited to
skin, this circuit can also facilitate rapid adaptive responses to external light
in other homeostatic tissues.
PMID- 29959213
TI - Combined VLA-4-Targeted Radionuclide Therapy and Immunotherapy in a Mouse Model
of Melanoma.
AB - Very late antigen-4 (VLA-4; also known as integrin alpha4beta1) is expressed at
high levels in aggressive and metastatic melanoma tumors and may provide an ideal
target for imaging and targeted radionuclide therapy (TRT). 177Lu-DOTA-PEG4-LLP2A
(177Lu-LLP2A) is a TRT that shows high affinity for VLA-4 and high uptake in
B16F10 mouse melanoma tumors in vivo. Here, we report efficacy studies of 177Lu
LLP2A, alone and combined with immune checkpoint inhibitors (ICIs) (anti-PD-1,
anti-PD-L1, and anti-CTLA-4 antibodies), in B16F10 tumor-bearing mice. Methods:
Tumor cells (1 * 106) were implanted subcutaneously in C57BL/6 mice. After 8-10
d, the mice were randomized into 8 groups. 177Lu-LLP2A was injected intravenously
on day 8 or 9 (single dose), and ICI antibodies were administered
intraperitoneally in 3 doses. Tumor growth was monitored over time via calipers.
Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining for
apoptosis was performed on fixed tumors. In a separate study, Cy3-LLP2A or Cy3
scrambled LLP2A was injected in tumor-bearing mice, and tumors were collected 4 h
after injection and then analyzed by flow cytometry and immunofluorescence
microscopy using different immune cell markers. Results: TRT alone showed
efficacy comparable to the dual-ICI anti-PD-1 + anti-CTLA-4 or anti-PD-L1 + anti
CTLA-4, whereas TRT + ICIs significantly enhanced survival. TUNEL staining showed
that the highest levels of apoptosis were in the TRT + ICI groups. In addition to
targeting tumor cells, TRT also bound immune cells in the tumor microenvironment.
Flow cytometry data showed that the tumors consisted of about 77% tumor cells and
fibroblasts (CD45-negative/CD49d-positive) and about 23% immune cells (CD45
positive/CD49d-positive) and that immune cells expressed higher levels of VLA-4.
Cy3-LLP2A and CD49d colocalized with macrophages (CD68), T cells (CD8, CD4), and
B cells (CD19). Immunohistochemical analysis identified a significant
colocalization of Cy3-LLP2A and CD68. Conclusion: Combination treatment with TRT
+ ICIs targets both tumor cells and immune cells and has potential as a
therapeutic agent in patients with metastatic melanoma.
PMID- 29959214
TI - Glycoprotein IIb/IIIa receptor imaging with 18F-GP1 positron emission tomography
for acute venous thromboembolism: an open-label, non-randomized, first-in-human
phase 1 study.
AB - 18F-GP1 is a derivative of elarofiban with a high affinity to activated platelet
glycoprotein IIb/IIIa (GPIIb/IIIa) and favorable in vivo characteristics for
thrombus imaging in preclinical models. We aimed to explore the detection rate of
thromboembolic foci with 18F-GP1 positron emission tomography/computed tomography
(PET/CT) in patients with acute venous thromboembolism (VTE), and to evaluate the
safety, biodistribution, pharmacokinetics, and metabolism of 18F-GP1. Methods: We
studied patients who had signs or symptoms of acute deep vein thrombosis (DVT) of
the leg or acute pulmonary embolism (PE) within 14 days prior to 18F-GP1 PET/CT,
and had thromboembolic foci confirmed by conventional imaging (n = 10 for DVT and
n = 10 for PE). Dynamic whole-body PET/CT images were acquired for up to 140
minutes after injection of 250 MBq of 18F-GP1. Results:18F-GP1 PET/CT was well
tolerated without any drug-related adverse events, and showed high initial uptake
in spleen, kidney, and blood pool, followed by rapid clearance. The overall image
quality was excellent and allowed interpretation in all patients. 18F-GP1 PET/CT
identified thromboembolic foci in all 20 patients with either DVT or PE. Vessel
level analysis revealed that 18F-GP1 PET/CT detected 89% (68/76) of vessels with
DVT, and 60% (146/245) for PE. Importantly, 18F-GP1 PET/CT showed increased
uptake in 32 vessels that were not detected by conventional imaging, of which 25
were located in distal veins of the lower extremity in 12 patients. A positive
correlation was found between 18F-GP1 uptake and P-selectin-positive circulating
platelets (r = 0.656, P = 0.002). Conclusion:18F-GP1 is a promising PET tracer
for imaging acute VTE in patients. 18F-GP1 PET/CT may identify thrombi in distal
veins of the leg, where conventional imaging has limitations.
PMID- 29959215
TI - Evaluation of Two Potent and Selective PET Radioligands to Image COX-1 and COX-2
in Rhesus Monkeys.
AB - This study assessed whether the newly developed PET radioligands 11C-PS13 and 11C
MC1 could image constitutive levels of cyclooxygenase (COX)-1 and COX-2,
respectively, in rhesus monkeys. Methods: After intravenous injection of either
radioligand, 24 whole-body PET scans were performed. To measure enzyme-specific
uptake, scans of the 2 radioligands were also performed after administration of a
nonradioactive drug preferential for either COX-1 or COX-2. Concurrent venous
samples were obtained to measure parent radioligand concentrations. SUVs were
calculated from 10 to 90 min. Results: 11C-PS13 showed specific uptake in most
organs, including spleen, gastrointestinal tract, kidneys, and brain, which was
blocked by COX-1, but not COX-2, preferential inhibitors. Specific uptake of 11C
MC1 was not observed in any organ except the ovaries and possibly kidneys.
Conclusion: The findings suggest that 11C-PS13 has adequate signal in monkeys to
justify its extension to human subjects. In contrast, 11C-MC1 is unlikely to show
significant signal in healthy humans, though it may be able to do so in
inflammatory conditions.
PMID- 29959216
TI - Targeting Micrometastases: The Effect of Heterogeneous Radionuclide Distribution
on Tumor Control Probability.
AB - The spatial distribution of radiopharmaceuticals that emit short-range high
linear-energy-transfer electrons greatly affects the absorbed dose and their
biological effectiveness. The purpose of this study was to investigate the effect
of heterogeneous radionuclide distribution on tumor control probability (TCP) in
a micrometastases model. Methods: Cancer cell lines; MDA-MB-468, SQ20B and 231
H2N were grown as spheroids to represent micrometastases. The intracellular
distribution of a representative radiopeptide (111In-labelled epidermal growth
factor, EGF) and radioimmunotherapeutic (111In-labelled Trastuzumab) was
determined in cell internalization experiments. The intratumoral distribution was
evaluated by microautoradiography of spheroids. gammaH2AX staining was performed
on spheroid sections to correlate DNA damage with radionuclide distribution.
Experimental surviving fractions (SFexp ) were obtained using clonogenic assays.
A random closed-packed algorithm, which models the random packing behavior of
cells and reflects variation in the radii of cells and nuclei, was used to
simulate 3-D spheroids. Calculated survival fractions (SFcal ) were generated
using an iterative modelling method based on Monte Carlo determined absorbed dose
with the PENELOPE code and were compared to (SFexp ). Radiobiological parameters
deduced from experimental results and MC simulations were used to predict the TCP
for a 3-D spheroid model. Results: Calculated SFs were in good agreement with
experimental data, particularly when an increased value for relative biological
effectiveness (RBE) was applied to self-dose deposited by sources located in the
nucleus and when radiobiological parameters were adjusted to account for dose
protraction. Only in MDA-MB-468 spheroids treated with 111In-EGF was a TCP>0.5
achieved, indicating that for this cell type the radiopeptide would be curative
when targeting micrometastases. This is attributed to the relative
radiosensitivity of MDA-MB-468 cells, high nuclear uptake of the radiopeptide and
uniform distribution of radioactivity throughout the spheroid. Conclusion: It is
imperative to include biological endpoints when evaluating the distribution of
radionuclides in models emulating micrometastatic disease. The spatial
distribution of radioactivity is a clear determinant of biological effect and TCP
as demonstrated in this study.
PMID- 29959217
TI - The Additional Value of PET in the Assessment of Cerebral Small Vessel Disease.
AB - The diagnosis of cerebral small vessel disease (SVD) is difficult because there
is no consensus on clinical criteria, and therefore imaging is important for
diagnosis. Most patients undergo brain imaging by CT, which is able to detect
ischemic strokes, hemorrhages, and brain atrophy and may also indicate white
matter changes. MRI remains the key neuroimaging modality and is preferred to CT
in vascular cognitive impairment (VCI) because it has higher sensitivity and
specificity for detecting pathologic changes. These modalities for imaging
morphology permit detection of vascular lesions traditionally attributed to VCI
in subcortical areas of the brain, single infarction or lacunes in strategic
areas (thalamus or angular gyrus), or large cortical-subcortical lesions reaching
a critical threshold of tissue loss. In SVD, multiple punctuate or confluent
lesions can be seen in the white matter by MRI and were called leukoaraiosis.
Another major neuroimaging finding of SVD in VCI are microhemorrhages. However,
whereas CT and MRI are able to detect morphologic lesions, these modalities
cannot determine functional consequences of the underlying pathologic changes.
PET can support the clinical diagnosis by visualizing cerebral functions in
typically affected brain regions. In SVD, 18F-FDG PET can clearly differentiate
scattered areas of focal cortical and subcortical hypometabolism that differ from
the typical metabolic pattern seen in Alzheimer dementia (AD) with marked
hypometabolism affecting the association areas. Additional PET tracers can
further support the diagnosis of a type of dementia and also yield information on
the underlying pathophysiology.
PMID- 29959218
TI - VT Substrate Characteristics: Insights from Multi-modality Structural and
Functional Imaging of the VT Substrate Using CMR Scar, 123I-mIBG-SPECT
Innervation and Bipolar Voltage.
AB - Background - Post-Ischemic adaptation results in characteristic myocardial
structural and functional changes of the VT(Ventricular Tachycardia) substrate.
Objective - Compare myocardial structural/functional adaptation (late gadolinium
enhancement(LGE)/abnormal innervation) with detailed VT mapping data to identify
regional heterogeneities of post-ischemic changes. Methods - Fifteen patients
with ischemic cardiomyopathy and drug-refractory VT underwent LGE-Cardiac
magnetic resonance imaging(CMR), 123I-mIBG-SPECT and high-resolution bipolar
voltage mapping to assess fibrosis(>3SD), abnormal innervation(<50% tracer
uptake) and low-voltage areas(<1.5mV), respectively. 3D-reconstructed CMR/123I
mIBG models were co-registered for further comparison. Results - Post-ischemic
structural/functional adaptation in all three categories was similar in size (CMR
scar 46.1cm2[33.1-86.9cm2] vs. 123I-mIBG-SPECT abnormal innervation 47.8cm2[40.5
68.1cm2] vs. low-voltage area 29.5cm2[24.5-102.6cm2], p>0.05). Yet, any single
modality underestimated the total VT substrate area, defined as abnormal in at
least one of the three modalities (76.0cm2[57.9-143.2cm2]; p<0.001). Within the
total VT substrate area, regions abnormal in all 3 modalities were most common
(25.2%). However, significant parts of the VT substrate had undergone
heterogeneous adaptation (abnormal in <3 modalities); most common categories were
'abnormal innervation only'(18.2%), 'CMR scar+abnormal innervation only'(14.9%)
and 'CMR scar only'(14.6%). All 14 VT channel/exit sites(0.88+/-0.74mV) localized
to myocardium demonstrating CMR scar AND abnormal innervation. This specific
tissue category accounted for 68.3% of the CMR scar and 31.2% of the total
abnormal post-ischemic VT substrate. Conclusion - Structural/functional imaging
demonstrates regional heterogeneities of the post-ischemic VT substrate not
appreciated by any single modality alone. Co-existence of abnormal innervation
and CMR scar may identify a state of particularly proarrhythmic adaptation and
represent a potential novel target for VT ablation.
PMID- 29959220
TI - MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis: mutant mice
challenging old paradigms.
AB - The two pituitary gonadotrophins, luteinizing hormone (LH) and follicle
stimulating hormone (FSH), and in particular LH-stimulated high intratesticular
testosterone (ITT) concentration, are considered crucial for spermatogenesis. We
have revisited these concepts in genetically modified mice, one being the LH
receptor (R)-knockout mouse (LuRKO), the other a transgenic mouse expressing in
Sertoli cells a highly constitutively active mutated Fshr (Fshr-CAM). It was
found that full spermatogenesis was induced by exogenous testosterone treatment
in LuRKO mice at doses that restored ITT concentration to a level corresponding
to the normal circulating testosterone level in WT mice, ~5 nmol/L, which is 1.4%
of the normal high ITT concentration. When hypogonadal LuRKO and Fshr-CAM mice
were crossed, the double-mutant mice with strong FSH signaling, but minimal
testosterone production, showed near-normal spermatogenesis, even when their
residual androgen action was blocked with the strong antiandrogen flutamide. In
conclusion, our findings challenge two dogmas of the hormonal regulation of male
fertility: (1) high ITT concentration is not necessary for spermatogenesis and
(2) strong FSH stimulation can maintain spermatogenesis without testosterone.
These findings have clinical relevance for the development of hormonal male
contraception and for the treatment of idiopathic oligozoospermia.
PMID- 29959221
TI - Intergenic Splicing between Four Adjacent UGT Genes (2B15, 2B29P2, 2B17, 2B29P1)
Gives Rise to Variant UGT Proteins That Inhibit Glucuronidation via Protein
Protein Interactions.
AB - Recent studies have investigated alternative splicing profiles of UDP
glucuronosyltransferase (UGT) genes and identified over 130 different
alternatively spliced UGT transcripts. Although UGT genes are highly clustered,
the formation of chimeric transcripts by intergenic splicing between two or more
UGT genes has not yet been reported. This study identified 12 chimeric
transcripts (chimeras A-L) containing exons from two or three genes of the four
neighboring UGT genes (UGT2B15, UGT2B29P2, UGT2B17, and UGT2B29P1) in human liver
and prostate cancer cells. These chimeras typically contain the first five exons
of UGT2B15 or UGT2B17 (exons 1-5) spliced to a terminal exon (exon 6) from a
downstream UGT gene. Hence they encode truncated UGTs with novel C-terminal
peptides. Functional assays of representative chimeric UGT proteins (termed
chimeric UGT2B15 and chimeric UGT2B17) showed that they are inactive and can
repress the activity of wild-type UGTs. Coimmunoprecipitation assays demonstrated
heterotypic interactions between chimeric UGT2B15 (or chimeric UGT2B17) and the
UGT2B7 protein. Thus oligomerization of the chimeric UGTs with wild-type UGTs may
explain their inhibitory activity. Studies in breast and prostate cancer cells
showed that both wild-type and chimeric UGT2B15 and UGT2B17 transcripts are
regulated in a similar way at the transcriptional level by sex hormones through
their canonical promoters but are differentially regulated at the post
transcriptional level by micro-RNA 376c via their unique 3'-untranslated regions.
In conclusion, the formation of chimeric transcripts by intergenic splicing among
UGT genes represents a novel mechanism contributing to the diversity of the human
UGT transcriptome and proteome. The differential post-transcriptional regulation
of wild-type and variant transcripts by micro-RNAs may contribute to their
deregulated expression in cancer.
PMID- 29959219
TI - RNase H2, mutated in Aicardi-Goutieres syndrome, promotes LINE-1
retrotransposition.
AB - Long INterspersed Element class 1 (LINE-1) elements are a type of abundant
retrotransposons active in mammalian genomes. An average human genome contains
~100 retrotransposition-competent LINE-1s, whose activity is influenced by the
combined action of cellular repressors and activators. TREX1, SAMHD1 and ADAR1
are known LINE-1 repressors and when mutated cause the autoinflammatory disorder
Aicardi-Goutieres syndrome (AGS). Mutations in RNase H2 are the most common cause
of AGS, and its activity was proposed to similarly control LINE-1
retrotransposition. It has therefore been suggested that increased LINE-1
activity may be the cause of aberrant innate immune activation in AGS Here, we
establish that, contrary to expectations, RNase H2 is required for efficient LINE
1 retrotransposition. As RNase H1 overexpression partially rescues the defect in
RNase H2 null cells, we propose a model in which RNase H2 degrades the LINE-1 RNA
after reverse transcription, allowing retrotransposition to be completed. This
also explains how LINE-1 elements can retrotranspose efficiently without their
own RNase H activity. Our findings appear to be at odds with LINE-1-derived
nucleic acids driving autoinflammation in AGS.
PMID- 29959222
TI - Nucleosome Positioning and Gene Regulation of the SGLT2 Gene in the Renal
Proximal Tubular Epithelial Cells.
AB - Filtered glucose is mostly reabsorbed by sodium-glucose cotransporter 2 (SGLT2)
in the proximal tubules. SGLT2 is predominantly expressed in the human kidney.
However, the regulatory mechanisms for SGLT2 gene expression in the human kidney
remain unclear. We in this work elucidated the transcriptional regulatory
mechanisms for the SGLT2 gene by nucleosome occupancy in the SGLT2 promoter
region. Expressions of SGLT2 mRNA and protein were markedly weaker in human
kidney-derived HK-2 cells than the human kidney. The nucleosome occupancy level
in the SGLT2 promoter region was low in the kidney, but high in HK-2 cells. A
treatment with a histone deacetylase inhibitor trichostatin A (TSA) decreased
nucleosome occupancy in the promoter region and increased SGLT2 expression levels
in HK-2 cells. The upregulation of SGLT2 expression by histone acetylation was
accompanied by a higher binding frequency of hepatocyte nuclear factor (HNF)
1alpha, a transcriptional modulator of SGLT2 in the human kidney, to the promoter
region. The transfection of a HNF1alpha expression plasmid into HK-2 cells
resulted in the upregulation of SGLT2 mRNA expression in the presence of TSA, but
not in the treatment of dimethylsulfoxide as a control. Nucleosome occupancy in
the promoter region was markedly higher in the liver and small intestine than the
kidney. Our results indicate that tissue-specific nucleosome occupancy plays an
important role in the regulation of SGLT2 gene expression via HNF1alpha binding
at the SGLT2 promoter region.
PMID- 29959223
TI - Long-Acting beta2-Adrenoceptor Agonists Enhance Glucocorticoid Receptor (GR)
Mediated Transcription by Gene-Specific Mechanisms Rather Than Generic Effects
via GR.
AB - In asthma, the clinical efficacy of inhaled corticosteroids (ICSs) is enhanced by
long-acting beta2-adrenoceptor agonists (LABAs). ICSs, or more accurately,
glucocorticoids, promote therapeutically relevant changes in gene expression,
and, in primary human bronchial epithelial cells (pHBECs) and airway smooth
muscle cells, this genomic effect can be enhanced by a LABA. Modeling this
interaction in human bronchial airway epithelial BEAS-2B cells transfected with a
2* glucocorticoid response element (2*GRE)-driven luciferase reporter showed
glucocorticoid-induced transcription to be enhanced 2- to 3-fold by LABA. This
glucocorticoid receptor (GR; NR3C1)-dependent effect occurred rapidly, was
insensitive to protein synthesis inhibition, and was maximal when glucocorticoid
and LABA were added concurrently. The ability of LABA to enhance GR-mediated
transcription was not associated with changes in GR expression, serine (Ser203,
Ser211, Ser226) phosphorylation, ligand affinity, or nuclear translocation.
Chromatin immunoprecipitation demonstrated that glucocorticoid-induced
recruitment of GR to the integrated 2*GRE reporter and multiple gene loci, whose
mRNAs were unaffected or enhanced by LABA, was also unchanged by LABA.
Transcriptomic analysis revealed glucocorticoid-induced mRNAs were variably
enhanced, unaffected, or repressed by LABA. Thus, events leading to GR binding at
target genes are not the primary explanation for how LABAs modulate GR-mediated
transcription. As many glucocorticoid-induced genes are independently induced by
LABA, gene-specific control by GR- and LABA-activated transcription factors may
explain these observations. Because LABAs promote similar effects in pHBECs,
therapeutic relevance is likely. These data illustrate the need to understand
gene function(s), and the mechanisms leading to gene-specific induction, if
existing ICS/LABA combination therapies are to be improved.
PMID- 29959224
TI - Glycation affects fibril formation of Abeta peptides.
AB - Increasing evidence shows that beta-amyloid (Abeta) peptides, which are
associated with Alzheimer disease (AD), are heavily glycated in patients,
suggesting a role of this irreversible nonenzymatic post-translational
modification in pathology. Previous reports have shown that glycation increases
the toxicity of the Abeta peptides, although little is known about the mechanism.
Here, we used the natural metabolic by-product methylglyoxal as a glycating agent
and exploited various spectroscopic methods and atomic force microscopy to study
how glycation affects the structures of the Abeta40 and Abeta42 peptides, the
aggregation pathway, and the morphologies of the resulting aggregates. We found
that glycation significantly slows down but does not prevent beta-conversion to
mature fibers. We propose that the previously reported higher toxicity of the
glycated Abeta peptides could be explained by a longer persistence in an
oligomeric form, usually believed to be the toxic species.
PMID- 29959225
TI - Glycosaminoglycans have variable effects on alpha-synuclein aggregation and
differentially affect the activities of the resulting amyloid fibrils.
AB - Parkinson's disease is mainly a sporadic disorder in which both environmental and
cellular factors play a major role in the initiation of this disease.
Glycosaminoglycans (GAG) are integral components of the extracellular matrix and
are known to influence amyloid aggregation of several proteins, including alpha
synuclein (alpha-Syn). However, the mechanism by which different GAGs and related
biological polymers influence protein aggregation and the structure and
intercellular spread of these aggregates remains elusive. In this study, we used
three different GAGs and related charged polymers to establish their role in
alpha-Syn aggregation and associated biological activities of these aggregates.
Heparin, a representative GAG, affected alpha-Syn aggregation in a concentration
dependent manner, whereas biphasic alpha-Syn aggregation kinetics was observed in
the presence of chondroitin sulfate B. Of note, as indicated by 2D NMR analysis,
different GAGs uniquely modulated alpha-Syn aggregation because of the diversity
of their interactions with soluble alpha-Syn. Moreover, subtle differences in the
GAG backbone structure and charge density significantly altered the properties of
the resulting amyloid fibrils. Each GAG/polymer facilitated the formation of
morphologically and structurally distinct alpha-Syn amyloids, which not only
displayed variable levels of cytotoxicity but also exhibited an altered ability
to internalize into cells. Our study supports the role of GAGs as key modulators
in alpha-Syn amyloid formation, and their distinct activities may regulate
amyloidogenesis depending on the type of GAG being up- or down-regulated in vivo.
PMID- 29959226
TI - Transcriptional burst fraction and size dynamics during lens fiber cell
differentiation and detailed insights into the denucleation process.
AB - Genes are transcribed in irregular pulses of activity termed transcriptional
bursts. Cellular differentiation requires coordinated gene expression; however,
it is unknown whether the burst fraction (i.e. the number of active phases of
transcription) or size/intensity (the number of RNA molecules produced within a
burst) changes during cell differentiation. In the ocular lens, the positions of
lens fiber cells correlate precisely with their differentiation status, and the
most advanced cells degrade their nuclei. Here, we examined the transcriptional
parameters of the beta-actin and lens differentiation-specific alpha-, beta-, and
gamma-crystallin genes by RNA fluorescent in situ hybridization (FISH) in the
lenses of embryonic day (E) E12.5, E14.5, and E16.5 mouse embryos and newborns.
We found that cellular differentiation dramatically alters the burst fraction in
synchronized waves across the lens fiber cell compartment with less dramatic
changes in burst intensity. Surprisingly, we observed nascent transcription of
multiple genes in nuclei just before nuclear destruction. Nuclear condensation
was accompanied by transfer of nuclear proteins, including histone and nonhistone
proteins, to the cytoplasm. Although lens-specific deletion of the chromatin
remodeler SWI/SNF-related matrix-associated actin-dependent regulator of
chromatin subfamily A member 5 (Smarca5/Snf2h) interfered with denucleation,
persisting nuclei remained transcriptionally competent and exhibited changes in
both burst intensity and fraction depending on the gene examined. Our results
uncover the mechanisms of nascent transcriptional control during differentiation
and chromatin remodeling, confirm the burst fraction as the major factor
adjusting gene expression levels, and reveal transcriptional competence of fiber
cell nuclei even as they approach disintegration.
PMID- 29959227
TI - The polycomb group protein Yaf2 regulates the pluripotency of embryonic stem
cells in a phosphorylation-dependent manner.
AB - The polycomb group (PcG) proteins are key epigenetic regulators in stem cell
maintenance. PcG proteins have been thought to act through one of two polycomb
repressive complexes (PRCs), but more recent biochemical analyses have challenged
this model in the identification of noncanonical PRC1 (nc-PRC1) complexes
characterized by the presence of Rybp or Yaf2 in place of the canonical Chromobox
proteins. However, the biological significance of these nc-PRC1s and the
potential mechanisms by which they mediate gene repression are largely unknown.
Here, we explore the functional consequences of Yaf2 disruption on stem cell
regulation. We show that deletion of Yaf2 results in compromised proliferation
and abnormal differentiation of mouse embryonic stem cells (mESCs). Genome-wide
profiling indicates Yaf2 functions primarily as a transcriptional repressor,
particularly impacting genes associated with ectoderm cell fate in a manner
distinct from Rybp. We confirm that Yaf2 assembles into a noncanonical PRC
complex, with deletion analysis identifying the region encompassing amino acid
residues 102-150 as required for this assembly. Furthermore, we identified serine
166 as a Yaf2 phosphorylation site, and we demonstrate that mutation of this site
to alanine (S166A) compromises Ring1B-mediated H2A monoubiquitination and in turn
its ability to repress target gene expression. We therefore propose that Yaf2 and
its phosphorylation status serve as dual regulators to maintain the pluripotent
state in mESCs.
PMID- 29959228
TI - Uncoupling fork speed and origin activity to identify the primary cause of
replicative stress phenotypes.
AB - In growing cells, DNA replication precedes mitotic cell division to transmit
genetic information to the next generation. The slowing or stalling of DNA
replication forks at natural or exogenous obstacles causes "replicative stress"
that promotes genomic instability and affects cellular fitness. Replicative
stress phenotypes can be characterized at the single-molecule level with DNA
combing or stretched DNA fibers, but interpreting the results obtained with these
approaches is complicated by the fact that the speed of replication forks is
connected to the frequency of origin activation. Primary alterations in fork
speed trigger secondary responses in origins, and, conversely, primary
alterations in the number of active origins induce compensatory changes in fork
speed. Here, by employing interventions that temporally restrict either fork
speed or origin firing while still allowing interrogation of the other variable,
we report a set of experimental conditions to separate cause and effect in any
manipulation that affects DNA replication dynamics. Using HeLa cells and chemical
inhibition of origin activity (through a CDC7 kinase inhibitor) and of DNA
synthesis (via the DNA polymerase inhibitor aphidicolin), we found that primary
effects of replicative stress on velocity of replisomes (fork rate) can be
readily distinguished from primary effects on origin firing. Identifying the
primary cause of replicative stress in each case as demonstrated here may
facilitate the design of methods to counteract replication stress in primary
cells or to enhance it in cancer cells to increase their susceptibility to
therapies that target DNA repair.
PMID- 29959229
TI - Identification of Rpl29 as a major substrate of the lysine methyltransferase
Set7/9.
AB - Set7/9 (also known as Set7, Set9, Setd7, and Kmt7) is a lysine methyltransferase
that catalyzes the methylation of multiple substrates, including histone H3 and
non-histone proteins. Although not essential for normal development and
physiology, Set7/9-mediated methylation events play important roles in regulating
cellular pathways involved in various human diseases, making Set7/9 a promising
therapeutic target. Multiple Set7/9 inhibitors have been developed, which exhibit
varying degrees of potency and selectivity in vitro However, validation of these
compounds in vivo has been hampered by the lack of a reliable cellular biomarker
for Set7/9 activity. Here, we report the identification of Rpl29, a ribosomal
protein abundantly expressed in all cell types, as a major substrate of Set7/9.
We show that Rpl29 lysine 5 (Rpl29K5) is methylated exclusively by Set7/9 and can
be demethylated by Lsd1 (also known as Kdm1a). Rpl29 is not a core component of
the ribosome translational machinery and plays a regulatory role in translation
efficiency. Our results indicate that Rpl29 methylation has no effect on global
protein synthesis but affects Rpl29 subcellular localization. Using an Rpl29
methylation-specific antibody, we demonstrate that Rpl29K5 methylation is present
ubiquitously and validate that (R)-PFI-2, a Set7/9 inhibitor, efficiently reduces
Rpl29K5 methylation in cell lines. Thus, Rpl29 methylation can serve as a
specific cellular biomarker for measuring Set7/9 activity.
PMID- 29959230
TI - Spontaneous refolding of the large multidomain protein malate synthase G proceeds
through misfolding traps.
AB - Most protein folding studies until now focus on single domain or truncated
proteins. Although great insights in the folding of such systems has been
accumulated, very little is known regarding the proteins containing multiple
domains. It has been shown that the high stability of domains, in conjunction
with inter-domain interactions, manifests as a frustrated energy landscape,
causing complexity in the global folding pathway. However, multidomain proteins
despite containing independently foldable, loosely cooperative sections can fold
into native states with amazing speed and accuracy. To understand the complexity
in mechanism, studies were conducted previously on the multidomain protein malate
synthase G (MSG), an enzyme of the glyoxylate pathway with four distinct and
adjacent domains. It was shown that the protein refolds to a functionally active
intermediate state at a fast rate, which slowly produces the native state.
Although experiments decoded the nature of the intermediate, a full description
of the folding pathway was not elucidated. In this study, we use a battery of
biophysical techniques to examine the protein's folding pathway. By using
multiprobe kinetics studies and comparison with the equilibrium behavior of
protein against urea, we demonstrate that the unfolded polypeptide undergoes
conformational compaction to a misfolded intermediate within milliseconds of
refolding. The misfolded product appears to be stabilized under moderate
denaturant concentrations. Further folding of the protein produces a stable
intermediate, which undergoes partial unfolding-assisted large segmental
rearrangements to achieve the native state. This study reveals an evolved folding
pathway of the multidomain protein MSG, which involves surpassing the multiple
misfolding traps during refolding.
PMID- 29959231
TI - CLIP and cohibin separate rDNA from nucleolar proteins destined for degradation
by nucleophagy.
AB - Nutrient starvation or inactivation of target of rapamycin complex 1 (TORC1) in
budding yeast induces nucleophagy, a selective autophagy process that
preferentially degrades nucleolar components. DNA, including ribosomal DNA
(rDNA), is not degraded by nucleophagy, even though rDNA is embedded in the
nucleolus. Here, we show that TORC1 inactivation promotes relocalization of
nucleolar proteins and rDNA to different sites. Nucleolar proteins move to sites
proximal to the nuclear-vacuolar junction (NVJ), where micronucleophagy (or
piecemeal microautophagy of the nucleus) occurs, whereas rDNA dissociates from
nucleolar proteins and moves to sites distal to NVJs. CLIP and cohibin, which
tether rDNA to the inner nuclear membrane, were required for repositioning of
nucleolar proteins and rDNA, as well as effective nucleophagic degradation of the
nucleolar proteins. Furthermore, micronucleophagy itself was necessary for the
repositioning of rDNA and nucleolar proteins. However, rDNA escaped from
nucleophagic degradation in CLIP- or cohibin-deficient cells. This study reveals
that rDNA-nucleolar protein separation is important for the nucleophagic
degradation of nucleolar proteins.
PMID- 29959232
TI - Time-resolved transcriptomics in neural stem cells identifies a v-ATPase/Notch
regulatory loop.
AB - Drosophila melanogaster neural stem cells (neuroblasts [NBs]) divide
asymmetrically by differentially segregating protein determinants into their
daughter cells. Although the machinery for asymmetric protein segregation is well
understood, the events that reprogram one of the two daughter cells toward
terminal differentiation are less clear. In this study, we use time-resolved
transcriptional profiling to identify the earliest transcriptional differences
between the daughter cells on their way toward distinct fates. By screening for
coregulated protein complexes, we identify vacuolar-type H+-ATPase (v-ATPase)
among the first and most significantly down-regulated complexes in
differentiating daughter cells. We show that v-ATPase is essential for NB growth
and persistent activity of the Notch signaling pathway. Our data suggest that v
ATPase and Notch form a regulatory loop that acts in multiple stem cell lineages
both during nervous system development and in the adult gut. We provide a unique
resource for investigating neural stem cell biology and demonstrate that cell
fate changes can be induced by transcriptional regulation of basic, cell
essential pathways.
PMID- 29959233
TI - Desmoplakin maintains gap junctions by inhibiting Ras/MAPK and lysosomal
degradation of connexin-43.
AB - Desmoplakin (DP) is an obligate component of desmosomes, intercellular adhesive
junctions that maintain the integrity of the epidermis and myocardium. Mutations
in DP can cause cardiac and cutaneous disease, including arrhythmogenic
cardiomyopathy (ACM), an inherited disorder that frequently results in deadly
arrhythmias. Conduction defects in ACM are linked to the remodeling and
functional interference with Cx43-based gap junctions that electrically and
chemically couple cells. How DP loss impairs gap junctions is poorly understood.
We show that DP prevents lysosomal-mediated degradation of Cx43. DP loss
triggered robust activation of ERK1/2-MAPK and increased phosphorylation of
S279/282 of Cx43, which signals clathrin-mediated internalization and subsequent
lysosomal degradation of Cx43. RNA sequencing revealed Ras-GTPases as candidates
for the aberrant activation of ERK1/2 upon loss of DP. Using a novel Ras
inhibitor, Ras/Rap1-specific peptidase (RRSP), or K-Ras knockdown, we demonstrate
restoration of Cx43 in DP-deficient cardiomyocytes. Collectively, our results
reveal a novel mechanism for the regulation of the Cx43 life cycle by DP in
cardiocutaneous models.
PMID- 29959234
TI - Neural Computations Underlying Causal Structure Learning.
AB - Behavioral evidence suggests that beliefs about causal structure constrain
associative learning, determining which stimuli can enter into association, as
well as the functional form of that association. Bayesian learning theory
provides one mechanism by which structural beliefs can be acquired from
experience, but the neural basis of this mechanism is poorly understood. We
studied this question with a combination of behavioral, computational, and
neuroimaging techniques. Male and female human subjects learned to predict an
outcome based on cue and context stimuli while being scanned using fMRI. Using a
model-based analysis of the fMRI data, we show that structure learning signals
are encoded in posterior parietal cortex, lateral prefrontal cortex, and the
frontal pole. These structure learning signals are distinct from associative
learning signals. Moreover, representational similarity analysis and information
mapping revealed that the multivariate patterns of activity in posterior parietal
cortex and anterior insula encode the full posterior distribution over causal
structures. Variability in the encoding of the posterior across subjects
predicted variability in their subsequent behavioral performance. These results
provide evidence for a neural architecture in which structure learning guides the
formation of associations.SIGNIFICANCE STATEMENT Animals are able to infer the
hidden structure behind causal relations between stimuli in the environment,
allowing them to generalize this knowledge to stimuli they have never experienced
before. A recently published computational model based on this idea provided a
parsimonious account of a wide range of phenomena reported in the animal learning
literature, suggesting a dedicated neural mechanism for learning this hidden
structure. Here, we validate this model by measuring brain activity during a task
that involves both structure learning and associative learning. We show that a
distinct network of regions supports structure learning and that the neural
signal corresponding to beliefs about structure predicts future behavioral
performance.
PMID- 29959235
TI - Ventral Hippocampal Inputs Preferentially Drive Corticocortical Neurons in the
Infralimbic Prefrontal Cortex.
AB - Inputs from the ventral hippocampus (vHPC) to the prefrontal cortex (PFC) play a
key role in working memory and emotional control. However, little is known about
how excitatory inputs from the vHPC engage different populations of neurons in
the PFC. Here we use optogenetics and whole-cell recordings to study the cell
type specificity of synaptic connections in acute slices from the mouse PFC. We
first show that vHPC inputs target pyramidal neurons whose cell bodies are
located in layer (L)2/3 and L5 of infralimbic (IL) PFC, but only in L5 of
prelimbic (PL) PFC, and not L6 of either IL or PL. We then compare connections
onto different classes of projection neurons located in these layers and
subregions of PFC. We establish vHPC inputs similarly contact corticocortical
(CC) and cortico-amygdala neurons in L2/3 of IL, but preferentially target CC
neurons over cortico-pontine neurons in L5 of both IL and PL. Of all these
neurons, we determine that vHPC inputs are most effective at driving action
potential (AP) firing of CC neurons in L5 of IL. We also show this connection
exhibits frequency-dependent facilitation, with repetitive activity enhancing AP
firing of IL L5 CC neurons, even in the presence of feedforward inhibition. Our
findings reveal how vHPC inputs engage defined populations of projection neurons
in the PFC, allowing preferentially activation of the intratelencephalic
network.SIGNIFICANCE STATEMENT We examined the impact of connections from the
ventral hippocampus (vHPC) onto different projection neurons in the mouse
prefrontal cortex (PFC). We found vHPC inputs were strongest at corticocortical
neurons in layer 5 of infralimbic PFC, where they robustly evoked action
potential firing, including during repetitive activity with intact feedforward
inhibition.
PMID- 29959238
TI - Neural processing of acoustic and electric interaural time differences in normal
hearing gerbils.
AB - Bilateral cochlear implants (CIs) provide benefits for speech perception in noise
and directional hearing, but users typically show poor sensitivity to interaural
time differences (ITDs). Possible explanations for this deficit are deafness
induced degradations in neural ITD sensitivity, between-ear mismatches in
electrode positions or activation sites, or differences in binaural brain
circuits activated by electric versus acoustic stimulation. To identify potential
limitations of electric ITD coding in the normal-hearing system, responses of
single neurons in the dorsal nucleus of the lateral lemniscus and the inferior
colliculus to ITDs of electric (biphasic pulses) and acoustic stimuli (noise,
clicks, chirps, and tones) were recorded in normal-hearing gerbils of either sex.
To maintain acoustic sensitivity, electric stimuli were delivered to the round
window.ITD tuning metrics (e.g., best ITD) and ITD discrimination thresholds for
electric versus transient acoustic stimuli (clicks, chirps), obtained from the
same neurons, were not significantly correlated. Across populations of neurons
with similar characteristic frequencies, however, ITD tuning metrics and ITD
discrimination thresholds were similar for electric and acoustic stimuli and
largely independent of the spectrotemporal properties of the acoustic stimuli,
when measured in the central range of ITDs. The similarity of acoustic and
electric ITD coding on the population level in animals with normal hearing
experience suggests that poorer ITD sensitivity in bilateral CI users compared to
normal-hearing listeners is likely due to deprivation-induced changes in neural
ITD coding rather than due to differences in the binaural brain circuits involved
in the processing of electric and acoustic ITDs.SIGNIFICANCE STATEMENTSmall
differences in the arrival time of sound at the two ears (interaural time
differences, ITDs) provide important cues for speech understanding in noise and
directional hearing. Deaf subjects with bilateral cochlear implants obtain only
little benefit from ITDs. It is unclear whether these limitations are due to
between-ear mismatches in activation sites, differences in binaural brain
circuits activated by electric versus acoustic stimulation, or deafness-induced
degradations in neural ITD processing. This study is the first to directly
compare electric and acoustic ITD coding in neurons of known characteristic
frequencies. In animals with normal hearing, populations of auditory brainstem
and midbrain neurons demonstrate general similarities in electric and acoustic
ITD coding suggesting similar underlying central auditory processing mechanisms.
PMID- 29959236
TI - Regional Distribution of CNS Antigens Differentially Determines T-Cell Mediated
Neuroinflammation in a CX3CR1-Dependent Manner.
AB - T cells continuously sample CNS-derived antigens in the periphery, yet it is
unknown how they sample and respond to CNS antigens derived from distinct brain
areas. We expressed ovalbumin (OVA) neoepitopes in regionally distinct CNS areas
(Cnp-OVA and Nes-OVA mice) to test peripheral antigen sampling by OVA-specific T
cells under homeostatic and neuroinflammatory conditions. We show that antigen
sampling in the periphery is independent of regional origin of CNS antigens in
both male and female mice. However, experimental autoimmune encephalomyelitis
(EAE) is differentially influenced in Cnp-OVA and Nes-OVA female mice. Although
there is the same frequency of CD45high CD11b+ CD11c+ CX3CL1+ myeloid cell-T-cell
clusters in neoepitope-expressing areas, EAE is inhibited in Nes-OVA female mice
and accelerated in CNP-OVA female mice. Accumulation of OVA-specific T cells and
their immunomodulatory effects on EAE are CX3C chemokine receptor 1 (CX3CR1)
dependent. These data show that despite similar levels of peripheral antigen
sampling, CNS antigen-specific T cells differentially influence neuroinflammatory
disease depending on the location of cognate antigens and the presence of
CX3CL1/CX3CR1 signaling.SIGNIFICANCE STATEMENT Our data show that peripheral T
cells similarly recognize neoepitopes independent of their origin within the CNS
under homeostatic conditions. Contrastingly, during ongoing autoimmune
neuroinflammation, neoepitope-specific T cells differentially influence clinical
score and pathology based on the CNS regional location of the neoepitopes in a
CX3CR1-dependent manner. Altogether, we propose a novel mechanism for how T cells
respond to regionally distinct CNS derived antigens and contribute to CNS
autoimmune pathology.
PMID- 29959239
TI - Safety investigation practices can be adapted from aviation for use in
healthcare.
PMID- 29959237
TI - Muscarinic receptor M3R signaling prevents efficient remyelination by human and
mouse oligodendrocyte progenitor cells.
AB - Muscarinic receptor antagonists act as potent inducers of oligodendrocyte
differentiation and accelerate remyelination. However, the use of muscarinic
antagonists in the clinic is limited by poor understanding of the operant
receptor subtype, and questions regarding possible species differences between
rodents and humans. Based on high selective expression in human oligodendrocyte
progenitor cells (OPCs), we hypothesized that M3R is the functionally relevant
receptor. Lentiviral M3R knock-down in human primary CD140a/PDGFalphaR+ OPCs
resulted in enhanced differentiation in vitro and substantially reduced the
calcium response following muscarinic agonist treatment. Importantly, following
transplantation in hypomyelinating shiverer/rag2 mice, M3R knock-down improved
remyelination by human OPCs. Furthermore, conditional M3R ablation in adult NG2
expressing OPCs increased oligodendrocyte differentiation and led to improved
spontaneous remyelination in mice. Together, we demonstrate that M3R receptor
mediates muscarinic signaling in human OPCs that act to delay differentiation and
remyelination, suggesting that M3 receptors are viable targets for human
demyelinating disease.SIGNIFICANCE STATEMENTThe identification of drug targets
aimed at improving remyelination in patients with demyelination disease is a key
step in development of effective regenerative therapies to treat diseases such as
multiple sclerosis. Muscarinic receptor antagonists have been identified as
effective potentiators of remyelination but the receptor subtypes that mediate
these receptors are unclear. In this study, Welliver et al. show that genetic M3R
ablation in both mouse and human cells results in improved remyelination and is
mediated by acceleration of oligodendrocyte commitment from oligodendrocyte
progenitor cells. Therefore, M3R therefore represents an attractive target for
induced remyelination in human disease.
PMID- 29959241
TI - Cys2His2 Zinc Finger Transcription Factor BcabaR1 Positively Regulates Abscisic
Acid Production in Botrytis cinerea.
AB - Abscisic acid (ABA) is one of the five classical phytohormones involved in
increasing the tolerance of plants for various kinds of stresses caused by
abiotic or biotic factors, and it also plays important roles in regulating the
activation of innate immune cells and glucose homeostasis in mammals. For these
reasons, as a "stress hormone," ABA has recently received attention as a
candidate drug for agriculture and biomedical applications, prompting significant
development of ABA synthesis. Some plant-pathogenic fungi can synthesize natural
ABA. The fungus Botrytis cinerea has been used for biotechnological production of
ABA. Identification of the transcription factors (TFs) involved in regulation of
ABA biosynthesis in B. cinerea would provide new clues to understand how ABA is
synthesized and regulated. In this study, we defined a novel Cys2His2 TF,
BcabaR1, that regulates the transcriptional levels of ABA synthase genes (bcaba1,
bcaba2, bcaba3, and bcaba4) in an ABA-overproducing mutant, B. cinerea TBC-A.
Electrophoretic mobility shift assays revealed that recombinant BcabaR1 can bind
specifically to both a 14-nucleotide sequence motif and a 39-nucleotide sequence
motif in the promoter region of bcaba1 to -4 genes in vitro A decreased
transcriptional level of the bcabaR1 gene in B. cinerea led to significantly
decreased ABA production and downregulated transcription of bcaba1 to -4 When
bcabaR1 was overexpressed in B. cinerea, ABA production was significantly
increased, with upregulated transcription of bcaba1 to -4 Thus, in this study, we
found that BcabaR1 acts as a positive regulator of ABA biosynthesis in B.
cinereaIMPORTANCE Abscisic acid (ABA) could make a potentially important
contribution to theoretical research and applications in agriculture and
medicine. Botrytis cinerea is a plant-pathogenic fungus that was found to produce
ABA. There has been a view that ABA is related to the interaction between
pathogenic fungi and plants. Identification of regulatory genes involved in ABA
biosynthesis may facilitate an understanding of the underlying molecular
mechanisms of ABA biosynthesis and the pathogenesis of B. cinerea Here, we
present a positive regulator, BcabaR1, of ABA biosynthesis in B. cinerea that can
affect the transcriptional level of the ABA biosynthesis gene cluster, bcaba1 to
4, by directly binding to the conserved sequence elements in the promoter of the
bcaba1 to -4 genes. This TF was found to be specifically involved in regulation
of ABA biosynthesis. This work provides new clues for finding other ABA
biosynthesis genes and improving ABA yield in B. cinerea.
PMID- 29959242
TI - Widely used benzalkonium chloride disinfectants can promote antibiotic
resistance.
AB - While misuse of antibiotics has clearly contributed to the emergence and
proliferation of resistant bacterial pathogens with major health consequences, it
remains less clear if the widespread use of disinfectants, a different class of
biocides than antibiotics such as benzalkonium chlorides (BAC), has contributed
to this problem. Here, we provide evidence that exposure to BAC co-selects for
antibiotic-resistant bacteria, and describe the underlying genetic mechanisms.
BAC-fed bioreactors inoculated with river sediment selected for several bacterial
taxa, including the opportunistic pathogen Pseudomonas aeruginosa, that were more
resistant to several antibiotics compared to their counterparts in a control (no
BAC) bioreactor. Metagenomic analysis of the bioreactor microbial communities,
confirmed by gene cloning experiments with the derived isolates, suggested that
integrative and conjugative elements encoding a BAC efflux pump together with
antibiotic resistance genes were responsible for these results. Further, exposure
of the P. aeruginosa isolates to increasing concentrations of BAC selected for
mutations in pmrB (polymyxin resistance) and physiological adaptations that
contributed to higher tolerance to polymyxin B and other antibiotics.
Physiological adaptations included, for example, the overexpression of mexCD-oprJ
multidrug efflux pump genes when BAC was added in the growth medium at sub
inhibitory concentrations. Collectively, our results demonstrated that
disinfectants can promote antibiotic resistance via several mechanisms, and
highlight the need to remediate (degrade) disinfectants in non-target
environments to further restrain the spread of antibiotic resistant
bacteria.IMPORTANCE Benzalkonium chlorides (BAC) are broadly used biocides in
disinfectant solutions. Disinfectants are widely used in food processing lines,
domestic households, and pharmaceuticals products, and are typically designed to
have a different mode of action than antibiotics in order to not interfere with
the use of the latter. Whether or not exposure to BAC makes bacteria more
resistant to antibiotics remains, however, an unresolved issue of obvious
practical consequences for public health. Using an integrated approach that
combined metagenomics of natural microbial communities with gene cloning
experiments with isolates and experimental evolution assays, we show that the
widely used benzalkonium chloride disinfectants can promote clinically-relevant
antibiotic resistance. Therefore, more attention should be given to the usage of
these disinfectants, and their fate in non-target environments should be more
tightly monitored.
PMID- 29959243
TI - Post-harvest Supply Chain with Microbial Travelers: A novel farm-to-retail
microbial simulation and visualization framework.
AB - Fresh produce supply chains present variable and diverse conditions that are
relevant to food quality and safety because they may favor microbial growth and
survival following contamination. This study presents development of a simulation
and visualization framework to model microbial dynamics on fresh produce moving
through post-harvest supply chain processes. The Post-harvest Supply Chain with
Microbial Travelers (PSCMT) tool provides a modular process modeling approach and
graphical user interface to visualize microbial populations and evaluate
practices specific to any fresh produce supply chain. The resulting modeling tool
was validated with empirical data from an observed tomato supply chain from
Mexico to USA, including the packinghouse, distribution center, and supermarket
locations, as an illustrative case study. Due to data limitations, a model
fitting exercise was conducted to demonstrate calibration of model parameter
ranges for microbial indicator populations, mesophilic aerobic microorganisms
(APC) and total coliforms (TC). Exploration and analysis of the parameter space
refined appropriate parameter ranges and revealed influential parameters for
supermarket indicator microorganism levels on tomatoes. Partial rank correlation
coefficient analysis determined APC supermarket levels were most influenced by
removal due to spray water washing and microbial growth on the tomato surface at
post-harvest locations, while TC levels were most influenced by growth on the
tomato surface at post-harvest locations. Overall, this detailed mechanistic
dynamic model of microbial behavior is a unique modeling tool that complements
empirical data and visualizes how post-harvest supply chain practices influence
the fate of microbial contamination on fresh produce.Importance: Preventing the
contamination of fresh produce with foodborne pathogens present in the
environment during production and post-harvest handling is an important food
safety goal. As studying foodborne pathogens in the environment is a complex and
costly endeavor, computer simulation models can help to understand and visualize
microorganism behavior resulting from supply chain activities. The Post-harvest
Supply Chain with Microbial Travelers (PSCMT), presented here, provides a unique
tool for post-harvest supply chain simulations to evaluate microbial
contamination. The tool was validated through modeling an observed tomato supply
chain. Visualization of dynamic contamination levels from harvest to the
supermarket and analysis of the model parameters highlighted critical points
where intervention may prevent microbial levels sufficient to cause foodborne
illness. The PSCMT model framework and simulation results support ongoing post
harvest research and interventions to improve understanding and control of fresh
produce contamination.
PMID- 29959244
TI - Evaluation of environmental sampling as a low technology method for surveillance
of Foot-and-mouth disease virus in an endemic area.
AB - Environmental sampling enables disease surveillance beyond regular investigation
of observed clinical cases, extending data on the circulation of a pathogen in a
specific area. Developing straightforward, low technology methods suitable for
use in field conditions is key to the inclusion of such approaches alongside
traditional surveillance techniques.Foot-and-mouth disease virus (FMDV) is an
economically important livestock pathogen, affecting cloven-hooved livestock in
many countries. Countries with FMDV face severe trade restrictions and infections
can result in long term effects on the productivity of affected animals.
Environmental contamination by virus in excretions and secretions from infected
individuals promotes transmission, but also presents an opportunity for non
invasive sample collection, facilitating diagnostic and surveillance purposes. We
present environmental sampling methods that have been tested in the Kathmandu
Valley, Nepal, where FMDV is endemic. A total of nine sites were visited and
sampled between November 2016 and November 2017. Environmental swabs collected
from sites with reported outbreaks of FMD were used to demonstrate successful
detection of FMDV RNA from the environment.Development of methods that can
reliably detect FMDV RNA in the environment is significant, as this extends the
toolbox available for surveillance for this disease. Similar methods have already
been deployed in the effort to eradicate polio and, in the case of FMDV, could
easily be deployed in the event of an outbreak to provide additional resources
for detection that would relieve pressure on veterinary services. Development of
low technology, straightforward surveillance methods such as this can support a
robust response to outbreaks.Importance Prompt confirmation and diagnosis of
disease are key factors in controlling outbreaks. Development of environmental
sampling techniques to detect FMDV RNA from the environment will extend the tool
kit available for surveillance of this pathogen. The methods presented in this
article broaden surveillance opportunities using accessible techniques. Pairing
these methods with existing and novel diagnostic tests will improve capability
for the rapid detection of outbreaks and implementation of timely interventions
to control outbreaks. In endemic areas, these methods can be implemented to
extend surveillance beyond the investigation of clinical cases, providing
additional data to assess virus circulation in specific areas.
PMID- 29959245
TI - UVC LED Irradiation Effectively Inactivates Aerosolized Viruses, Bacteria, and
Fungi in a Chamber-Type Air Disinfection System.
AB - In this study, the possibility of inactivating viral, bacterial, and fungal
aerosols in a chamber-type air disinfection system by using a UVC light-emitting
diode (LED) array was investigated and inactivation rate constants of each
microorganism were calculated in fitting curves of surviving populations. UVC LED
array treatment effectively inactivated viral infectivity, achieving 5-log
reductions within 45 mJ/cm2 for MS2, Qbeta, and phiX174 viruses. UVC LED array
effectiveness in inactivating Escherichia coli O157:H7, Salmonella enterica
serovar Typhimurium, Listeria monocytogenes, and Staphylococcus aureus aerosols
achieved 2.5- to 4-log reductions within 1.5 to 4.6 mJ/cm2 Also, 4-log reductions
of Aspergillus flavus and Alternaria japonica were achieved at a dosage of 23
mJ/cm2 using UVC LED array irradiation. The highest UV susceptibility,
represented by the inactivation rate constant, was calculated for bacteria,
followed by fungi and viruses. UVC LED, an innovative technology, can effectively
inactivate microorganisms regardless of taxonomic classification and can
sufficiently substitute for conventional mercury UV lamps.IMPORTANCE The United
Nations Environment Programme (UNEP) convened the Minamata Convention on Mercury
in 2013 to ban mercury-containing products in order to ensure human and
environmental health. It will be effectuated in 2020 to discontinue use of low
pressure mercury lamps and new UV-emitting sources have to replace this
conventional technology. However, the UV germicidal irradiation (UVGI) system
still uses conventional UV lamps, and no research has been conducted for air
disinfection using UVC LEDs. The research reported here investigated the
inactivation effect of aerosolized microorganisms, including viruses, bacteria,
and fungi, with an UVC LED module. The results can be utilized as a primary
database to replace conventional UV lamps with UVC LEDs, a novel type of UV
emitter. Implementation of UVC LED technology is truly expected to significantly
reduce the extent of global mercury contamination, and this study provides
important baseline data to help ensure a healthier environment and increased
health for humanity.
PMID- 29959246
TI - Overlapping Community Compositions of Gut and Fecal Microbiomes in Lab-Reared and
Field-Collected German Cockroaches.
AB - German cockroaches, Blattella germanica (Blattodea: Ectobiidae), are human
commensals that move freely between food and waste, disseminating bacteria,
including potential pathogens, through their feces. However, the relationship
between the microbial communities of the cockroach gut and feces is poorly
understood. We analyzed the V4 region of the 16S rRNA gene and the V9 region of
the 18S rRNA gene by next-generation sequencing (NGS) to compare the bacterial
and protist diversities in guts versus feces and males versus females, as well as
assess variation across cockroach populations. Cockroaches harbored a diverse
array of bacteria, and 80 to 90% of the operational taxonomic units (OTUs) were
shared between the feces and gut. Lab-reared and field-collected cockroaches had
distinct microbiota, and whereas lab-reared cockroaches had relatively conserved
communities, considerable variation was observed in the microbial community
composition of cockroaches collected in different apartments. Nonetheless,
cockroaches from all locations shared some core bacterial taxa. The eukaryotic
community in the feces of field-collected cockroaches was found to be more
diverse than that in lab-reared cockroaches. These results demonstrate that
cockroaches disseminate their gut microbiome in their feces, and they underscore
the important contribution of the cockroach fecal microbiome to the microbial
diversity of cockroach-infested homes.IMPORTANCE The German cockroach infests
diverse human-built structures, including homes and hospitals. It produces potent
allergens that trigger asthma and disseminates opportunistic pathogens in its
feces. A comprehensive understanding of gut and fecal microbial communities of
cockroaches is essential not only to understand their contribution to the biology
of the cockroach, but also for exploring their clinical relevance. In this study,
we compare the diversity of bacteria and eukaryotes in the cockroach gut and
feces and assess the variation in the gut microbiota across cockroach
populations.
PMID- 29959247
TI - Spodoptera frugiperda (J. E. Smith) Aminopeptidase N1 Is a Functional Receptor of
the Bacillus thuringiensis Cry1Ca Toxin.
AB - Bacillus thuringiensis Cry1Ca is toxic to different Spodoptera species. The aims
of this work were to identify the Cry1Ca-binding proteins in S. frugiperda, to
provide evidence on their participation in toxicity, and to identify the Cry1Ca
amino acid residues involved in receptor binding. Pulldown assays using
Spodoptera frugiperda brush border membrane vesicles (BBMV) identified
aminopeptidase N (APN), APN1, and APN2 isoforms as Cry1Ca-binding proteins.
Cry1Ca alanine substitutions in all residues of domain III beta16 were
characterized. Two beta16 nontoxic mutants (V505A and S506A) showed a correlative
defect on binding to the recombinant S. frugiperda APN1 (SfAPN1). Finally,
silencing the expression of APN1 transcript, by double-stranded RNA (dsRNA)
feeding, showed that silenced larvae are more tolerant of the Cry1Ca toxin, which
induced less than 40% mortality in silenced larvae whereas nonsilenced larvae had
100% mortality. Overall, our results show that Cry1Ca relies on APN1 binding
through domain III beta16 to impart toxicity to S. frugiperdaIMPORTANCEBacillus
thuringiensis Cry toxins rely on receptor binding to exert toxicity. Cry1Ca is
toxic to different populations of S. frugiperda, a major corn pest in America.
Nevertheless, the S. frugiperda midgut proteins that are involved in Cry1Ca
toxicity have not been identified. Here we identified aminopeptidase N1 (APN1) as
a functional receptor of Cry1Ca. Moreover, we showed that Cry1Ca domain III
beta16 is involved in APN1 binding. These results give insights on potential
target sites for improving Cry1Ca toxicity to S. frugiperda.
PMID- 29959248
TI - Maternal Soluble Fiber Diet during Pregnancy Changes the Intestinal Microbiota,
Improves Growth Performance, and Reduces Intestinal Permeability in Piglets.
AB - Increasing evidence suggests that maternal diet during pregnancy modifies
offspring's microbiota composition and intestinal development in a long-term
manner. However, the effects of maternal soluble fiber diet during pregnancy on
growth traits and the developing intestine are still underexplored. Sows were
allocated to either control or 2.0% pregelatinized waxy maize starch plus guar
gum (SF) dietary treatment during gestation. Growth performance, diarrhea
incidence, gut microbiota composition and metabolism, and gut permeability and
inflammation status of 14-day-old suckling piglets were analysed. The maternal SF
diet improved growth rate but decreased diarrhea incidence of piglets. Next
generation sequencing analysis revealed that the intestinal microbiota
composition was altered by a maternal SF diet. The fecal and plasma levels of
acetate and butyrate were also increased. Furthermore, a maternal SF diet reduced
the levels of plasma zonulin and fecal lipocalin-2 but increased the plasma
concentrations of interleukin 10 (IL-10) and transforming growth factor beta (TGF
beta). Additionally, the increased relative abundances of Lactobacillus in SF
piglets were positively correlated with growth rate while the decreased Bilophila
was positively correlated with fecal lipocalin-2. Our data reveal that a maternal
SF diet during pregnancy has remarkable effects on offspring's growth traits,
intestinal permeability and inflammation may via modulating the composition and
metabolism of gut microbiota.IMPORTANCE Although the direct effects of dietary
soluble fiber on gut microbiota have been extensively studied, the more indirect
effects of maternal nutrition during pregnancy independently on the development
of the intestine are until now largely unexplored. Our data show that a maternal
soluble fiber diet during pregnancy is independently associated with changes in
intestinal microbiota composition and metabolism of suckling piglets. These
findings have direct implications for refining dietary recommendations in
pregnancy. Moreover, a maternal soluble fiber diet reduces intestinal
permeability, prevents intestinal inflammation and excessive systemic immune
response of suckling piglets. Therefore, the suckling piglets' resistance to
disease was enhanced, diarrhea was reduced and weight gain was raised.
Additionally, the changes of gut microbiota in response to a maternal soluble
fiber diet may also direct correlated with the offspring's growth and gut
development.
PMID- 29959249
TI - Formation of Sublethally Injured Yersinia enterocolitica, Escherichia coli
O157:H7, and Salmonella enterica Serovar Enteritidis Cells after Neutral
Electrolyzed Oxidizing Water Treatments.
AB - The impact of neutral electrolyzed oxidizing (NEO) water treatments on the
formation of sublethally injured Yersinia enterocolitica, Escherichia coli
O157:H7, and Salmonella enterica serovar Enteritidis cells was evaluated. When
pathogens were treated with 6% NEO water, approximately 38% of the treated
Yersinia population and 25% of the treated Salmonella population became
sublethally injured. The highest sublethally injured population was found when
Salmonella cultures were treated with 3% NEO water. Regardless of the NEO water
concentration used, no sublethally injured E. coli O157:H7 cells were found. To
evaluate the sensitivity of NEO water-treated cells, four additional stresses
(heat treatment, pH, NaCl, and bile salt) were tested. NEO water treatments did
not generate any cross protection of treated cells against the other stresses.
The diluted NEO water treatments in combination with heat treatment at 51 degrees
C for 10 min led to the best synergistic antimicrobial effects with a combined
reduction of 7 logs. The gene expression results showed that NEO water treatments
led to the upregulation of ompR, ail, and ycfR These genes are known for their
involvement in cells' environmental stress responses. In summary, this study
investigated the sublethal injury in pathogenic cells caused by NEO water
treatments. Although sublethal injury was discovered, when combined with other
mild stresses, the synergistic antimicrobial effects were able to further reduce
the numbers of viable pathogenic cells. These results demonstrate the great
application potential of NEO water as a nonthermal and less corrosive
antimicrobial treatment.IMPORTANCE Neutral electrolyzed oxidizing (NEO) water is
a nonthermal and less corrosive antimicrobial treatment that has been
demonstrated to have efficacy in reducing microbial contamination in food,
including meat, fresh fruit, and vegetables. However, NEO water treatments can
cause sublethal injury to pathogenic cells, resulting in cells that retain their
viability. Consequently, these sublethally injured pathogenic cells become a
serious food safety concern. This study evaluated the formation of sublethally
injured Yersinia enterocolitica, Escherichia coli O157:H7, and Salmonella
enterica serovar Enteritidis cells by NEO water treatments and the potential
cross protection against heat, pH, NaCl, or bile salt stresses that it may
generate. No cross protection was observed. By combining NEO water treatments
with sublethal levels of additional stresses, significant synergistic
antimicrobial outcomes were achieved. These results indicate that mild processing
treatments, when combined, can effectively reduce pathogen populations while
minimizing the negative impacts on food quality.
PMID- 29959250
TI - iTRAQ-Based Global Proteomic Analysis of Salmonella enterica Serovar Typhimurium
in Response to Desiccation, Low Water Activity, and Thermal Treatment.
AB - In this study, the changes in the global proteome of Salmonella in response to
desiccation and thermal treatment were investigated by using an iTRAQ multiplex
technique. A Salmonella enterica serovar Typhimurium strain was dried,
equilibrated at high (1.0) and low (0.11) water activity (aw), and thermally
treated at 75 degrees C. The proteomes were characterized after every treatment.
The proteomes of the different treatments differed in the expression of 175
proteins. On the basis of their proteomic expression profiles, the samples were
clustered into two major groups, namely, "dry" samples and "moist" samples. The
groups had different levels of proteins involved in DNA synthesis and
transcription and in metabolic reactions, indicating that cells under either of
the aw conditions need to strictly control energy metabolism, the rate of
replication, and protein synthesis. The proteins with higher expression levels in
moist samples were flagellar proteins (FlgEFGH), membrane proteins, and export
systems (SecF, SecD, the Bam complex), as well as stress response proteins,
suggesting that rehydration can trigger stress responses in moist cells. Dry
samples had higher levels of ribosomal proteins, indicating that ribosomal
proteins might be important for additional regulation of the cellular response,
even when the synthesis of proteins is slowed down. At both aws, no differences
in protein expression were observed between the thermally treated samples and the
nonheated cells. In conclusion, our study indicates that the preadaptation to a
dry condition was linked to increased thermal tolerance, while reversion from a
dry state to a moist state induced a significant change in protein expression,
possibly linked to the observed loss of thermal tolerance.IMPORTANCESalmonella
enterica is able to survive in dry environments for very long periods. While it
is well known that the initial exposure to desiccation is fundamental to trigger
thermal tolerance in this organism, the specific physiological and molecular
processes involved in this cross-protection phenomenon have not been fully
characterized. Several studies have focused on the low-aw transcriptome of this
pathogen when inoculated in different food matrices or on abiotic surfaces, but
proteomic analyses have not been reported in the literature. Our study
investigated the changes in proteomic expression in Salmonella enterica serovar
Typhimurium during desiccation, exposure to low aw, and thermal treatment. A
better knowledge of the systems involved in the response to desiccation and
thermal tolerance, as well as a better understanding of their interplay, is
fundamental to identify the most effective combination of interventions to
prevent Salmonella's contamination of foods.
PMID- 29959251
TI - Environmental Controls on Soil Microbial Communities in a Seasonally Dry Tropical
Forest.
AB - Several studies have shown that rainfall seasonality, soil heterogeneity, and
increased nitrogen (N) deposition may have important effects on tropical forest
function. However, the effects of these environmental controls on soil microbial
communities in seasonally dry tropical forests are poorly understood. In a
seasonally dry tropical forest in the Yucatan Peninsula (Mexico), we investigated
the influence of soil heterogeneity (which results in two different soil types,
black and red soils), rainfall seasonality (in two successive seasons, wet and
dry), and 3 years of repeated N enrichment on soil chemical and microbiological
properties, including bacterial gene content and community structure. The soil
properties varied with the soil type and the sampling season but did not respond
to N enrichment. Greater organic matter content in the black soils was associated
with higher microbial biomass, enzyme activities, and abundances of genes related
to nitrification (amoA) and denitrification (nirK and nirS) than were observed in
the red soils. Rainfall seasonality was also associated with changes in soil
microbial biomass and activity levels and N gene abundances. Actinobacteria,
Proteobacteria, Firmicutes, and Acidobacteria were the most abundant phyla.
Differences in bacterial community composition were associated with soil type and
season and were primarily detected at higher taxonomic resolution, where specific
taxa drive the separation of communities between soils. We observed that soil
heterogeneity and rainfall seasonality were the main correlates of soil bacterial
community structure and function in this tropical forest, likely acting through
their effects on soil attributes, especially those related to soil organic matter
and moisture content.IMPORTANCE Understanding the response of soil microbial
communities to environmental factors is important for predicting the contribution
of forest ecosystems to global environmental change. Seasonally dry tropical
forests are characterized by receiving less than 1,800 mm of rain per year in
alternating wet and dry seasons and by high heterogeneity in plant diversity and
soil chemistry. For these reasons, N deposition may affect their soils
differently than those in humid tropical forests. This study documents the
influence of rainfall seasonality, soil heterogeneity, and N deposition on soil
chemical and microbiological properties in a seasonally dry tropical forest. Our
findings suggest that soil heterogeneity and rainfall seasonality are likely the
main factors controlling soil bacterial community structure and function in this
tropical forest. Nitrogen enrichment was likely too low to induce significant
short-term effects on soil properties, because this tropical forest is not N
limited.
PMID- 29959252
TI - Uncoupling Fermentative Synthesis of Molecular Hydrogen from Biomass Formation in
Thermotoga maritima.
AB - When carbohydrates are fermented by the hyperthermophilic anaerobe Thermotoga
maritima, molecular hydrogen (H2) is formed in strict proportion to substrate
availability. Excretion of the organic acids acetate and lactate provide an
additional sink for removal of excess reductant. However, mechanisms controlling
energy management of these metabolic pathways are largely unexplored. To
investigate this topic, transient gene inactivation was used to block lactate
production as a strategy to produce spontaneous mutant cell lines that
overproduced H2 through mutation of unpredicted genetic targets. Single-crossover
homologous chromosomal recombination was used to disrupt lactate dehydrogenase
(encoded by ldh) with a truncated ldh fused to a kanamycin resistance cassette
expressed from a native P groESL promoter. Passage of the unstable recombinant
resulted in loss of the genetic marker and recovery of evolved cell lines,
including strain Tma200. Relative to the wild type, and considering the mass
balance of fermentation substrate and products, Tma200 grew more slowly, produced
H2 at levels above the physiologic limit, and simultaneously consumed less
maltose while oxidizing it more efficiently. Whole-genome resequencing indicated
that the ABC maltose transporter subunit, encoded by malK3, had undergone
repeated mutation, and high-temperature anaerobic [14C]maltose transport assays
demonstrated that the rate of maltose transport was reduced. Transfer of the
malK3 mutation into a clean genetic background also conferred increased H2
production, confirming that the mutant allele was sufficient for increased H2
synthesis. These data indicate that a reduced rate of maltose uptake was
accompanied by an increase in H2 production, changing fermentation efficiency and
shifting energy management.IMPORTANCE Biorenewable energy sources are of growing
interest to mitigate climate change, but like other commodities with nominal
value, require innovation to maximize yields. Energetic considerations constrain
production of many biofuels, such as molecular hydrogen (H2) because of the
competing needs for cell mass synthesis and metabolite formation. Here we
describe cell lines of the extremophile Thermotoga maritima that exceed the
physiologic limits for H2 formation arising from genetic changes in fermentative
metabolism. These cell lines were produced using a novel method called transient
gene inactivation combined with adaptive laboratory evolution. Genome
resequencing revealed unexpected changes in a maltose transport protein. Reduced
rates of sugar uptake were accompanied by lower rates of growth and enhanced
productivity of H2.
PMID- 29959253
TI - Towards the Response Threshold for p-Hydroxyacetophenone in the Denitrifying
Bacterium "Aromatoleum aromaticum" EbN1.
AB - The denitrifying betaproteobacterium "Aromatoleum aromaticum" EbN1 regulates the
capacity to anaerobically degrade p-ethylphenol (via p-hydroxyacetophenone) with
high substrate specificity. This process is mediated by the sigma54-dependent
transcriptional regulator EtpR, which apparently recognizes both aromatic
compounds, yielding congruent expression profiles. The responsiveness of this
regulatory system was studied with p-hydroxyacetophenone, which is more easily
administered to cultures and traced analytically. Cultures of A. aromaticum EbN1
were initially cultivated under nitrate-reducing conditions with a growth
limiting supply of benzoate, upon the complete depletion of which p
hydroxyacetophenone was added at various concentrations (from 500 MUM down to 0.1
nM). Depletion profiles of this aromatic substrate and presumptive effector were
determined by highly sensitive micro-high-performance liquid chromatography
(microHPLC). Irrespective of the added concentration of p-hydroxyacetophenone,
depletion commenced after less than 5 min and suggested a response threshold of
below 10 nM. This approximation was corroborated by time-resolved transcript
profiles (quantitative reverse transcription-PCR) of selected degradation and
efflux relevant genes (e.g., pchF, encoding a subunit of predicted p-ethylphenol
methylenehydroxylase) and narrowed down to a range of 10 to 1 nM. The most
pronounced transcriptional response was observed, as expected, for genes located
at the beginning of the two operon-like structures, related to catabolism (i.e.,
acsA) and potential efflux (i.e., ebA335).IMPORTANCE Aromatic compounds are
widespread microbial growth substrates with natural as well as anthropogenic
sources, albeit with their in situ concentrations and their bioavailabilities
varying over several orders of magnitude. Even though degradation pathways and
underlying regulatory systems have long been studied with aerobic and, to a
lesser extent, with anaerobic bacteria, comparatively little is known about the
effector concentration-dependent responsiveness. A. aromaticum EbN1 is a model
organism for the anaerobic degradation of aromatic compounds with the
architecture of the catabolic network and its substrate-specific regulation
having been intensively studied by means of differential proteogenomics. The
present study aims at unraveling the minimal concentration of an aromatic growth
substrate (p-hydroxyacetophenone here) required to initiate gene expression for
its degradation pathway and to learn in principle about the lower limit of
catabolic responsiveness of an anaerobic degradation specialist.
PMID- 29959254
TI - High-Throughput Microfluidic Sorting of Live Magnetotactic Bacteria.
AB - Magnetic nanoparticles (MNPs) are useful for many biomedical applications, but it
is challenging to synthetically produce them in large numbers with uniform
properties and surface functionalization. Magnetotactic bacteria (MTB) produce
magnetosomes with homogenous sizes, shapes, and magnetic properties.
Consequently, there is interest in using MTB as biological factories for MNP
production. Nonetheless, MTB can only be grown to low yields, and wild-type
strains produce low numbers of MNPs/bacterium. There are also limited
technologies to facilitate the selection of MTB with different magnetic contents,
such as MTB with compromised and enhanced biomineralization ability. Here, we
describe a magnetic microfluidic platform combined with transient cold/alkaline
treatment to temporarily reduce the rapid flagellar motion of MTB without
compromising their long-term proliferation and biomineralization ability for
separating MTB on the basis of their magnetic contents. This strategy enables
live MTB to be enriched, which, to the best of our knowledge, has not been
achieved with another previously described magnetic microfluidic device that
makes use of ferrofluid and heat. Our device also facilitates the high-throughput
(25,000 cells/min) separation of wild-type Magnetospirillum gryphiswaldense (MSR
1) from nonmagnetic DeltamamAB MSR-1 mutants with a sensitivity of up to 80% and
isolation purity of up to 95%, as confirmed with a gold-standard fluorescent
activated cell sorter (FACS) technique. This offers a 25-fold higher throughput
than other previously described magnetic microfluidic platforms (1,000
cells/min). The device can also be used to isolate Magnetospirillum magneticum
(AMB-1) mutants with different ranges of magnetosome numbers with efficiencies
close to theoretical estimates. We believe this technology will facilitate the
magnetic characterization of genetically engineered MTB for a variety of
applications, including using MTB for large-scale, controlled MNP
production.IMPORTANCE Our magnetic microfluidic technology can greatly facilitate
biological applications with magnetotactic bacteria, from selection and screening
to analysis. This technology will be of interest to microbiologists, chemists,
and bioengineers who are interested in the biomineralization and selection of
magnetotactic bacteria (MTB) for applications such as directed evolution and
magnetogenetics.
PMID- 29959255
TI - Galacturonate Metabolism in Anaerobic Chemostat Enrichment Cultures: Combined
Fermentation and Acetogenesis by the Dominant sp. nov. "Candidatus
Galacturonibacter soehngenii".
AB - Agricultural residues such as sugar beet pulp and citrus peel are rich in pectin,
which contains galacturonic acid as a main monomer. Pectin-rich residues are
underexploited as feedstocks for production of bulk chemicals or biofuels. The
anaerobic, fermentative conversion of d-galacturonate in anaerobic chemostat
enrichment cultures provides valuable information toward valorization of these
pectin-rich feedstocks. Replicate anaerobic chemostat enrichments, with d
galacturonate as the sole limiting carbon source and inoculum from cow rumen
content and rotting orange peels, yielded stable microbial communities, which
were dominated by a novel Lachnospiraceae species, for which the name "Candidatus
Galacturonibacter soehngenii" was proposed. Acetate was the dominant catabolic
product, with formate and H2 as coproducts. The observed molar ratio of acetate
and the combined amounts of H2 and formate deviated significantly from 1, which
suggested that some of the hydrogen and CO2 formed during d-galacturonate
fermentation was converted into acetate via the Wood-Ljungdahl acetogenesis
pathway. Indeed, metagenomic analysis of the enrichment cultures indicated that
the genome of "Candidatus G. soehngenii" encoded enzymes of the adapted Entner
Doudoroff pathway for d-galacturonate metabolism as well as enzymes of the Wood
Ljungdahl pathway. The simultaneous operation of these pathways may provide a
selective advantage under d-galacturonate-limited conditions by enabling a higher
specific ATP production rate and lower residual d-galacturonate concentration
than would be possible with a strictly fermentative metabolism of this carbon and
energy source.IMPORTANCE This study on d-galacturonate metabolism by open, mixed
culture enrichments under anaerobic, d-galacturonate-limited chemostat conditions
shows a stable and efficient fermentation of d-galacturonate into acetate as the
dominant organic fermentation product. This fermentation stoichiometry and
population analyses provide a valuable baseline for interpretation of the
conversion of pectin-rich agricultural feedstocks by mixed microbial cultures.
Moreover, the results of this study provide a reference for studies on the
microbial metabolism of d-galacturonate under different cultivation regimes.
PMID- 29959258
TI - Not all, but specific types of cognitive complaints predict decline to MCI.
PMID- 29959257
TI - Subjective cognitive decline and risk of MCI: The Mayo Clinic Study of Aging.
AB - OBJECTIVE: We investigated different dimensions of subjective cognitive decline
(SCD) to determine which was the best prognostic risk factor for incident mild
cognitive impairment (MCI) among cognitively unimpaired participants. METHODS: We
included 1,167 cognitively unimpaired participants, aged 70 to 95 years, from the
Mayo Clinic Study of Aging based on 2 concurrent SCD scales (part of the Blessed
memory test and the 39-item Everyday Cognition [ECog] scale, which included a
validated 12-item derivative) and a single question assessing worry about
cognitive decline. We evaluated multiple ways to dichotomize scores. In
continuous models, we compared average scores on 4 ECog domains and multidomain
(39- and 12-item) ECog scores. Cox proportional hazards models were used to
assess the association between each measure and risk of MCI in models adjusted
for objective memory performance, depression, anxiety, sex, APOE epsilon4
carriership, and medical comorbidities. RESULTS: It was possible to select a
substantial group of participants (14%) at increased risk of incident MCI based
on combined baseline endorsement of any consistent SCD on the ECog (any item
scored >=3; 12-item ECog hazard ratio [HR] 2.17 [95% confidence interval 1.51
3.13]) and worry (HR 1.79 [1.24-2.58]) in an adjusted model combining these
dimensions. In continuous models, all ECog domains and the multidomain scores
were associated with risk of MCI with a small advantage for multidomain SCD (12
item ECog HR 2.13 [1.36-3.35] per point increase in average score). Information
provided by the informant performed comparable to self-perceived SCD. CONCLUSION:
Prognostic value of SCD for incident MCI improves when both consistency of SCD
and associated worry are evaluated.
PMID- 29959256
TI - "Candidatus Nitrosotenuis aquarius," an Ammonia-Oxidizing Archaeon from a
Freshwater Aquarium Biofilter.
AB - Ammonia is a metabolic waste product excreted by aquatic organisms that causes
toxicity when it accumulates. Aquaria and aquaculture systems therefore use
biological filters that promote the growth of nitrifiers to convert ammonia to
nitrate. Ammonia-oxidizing bacteria (AOB) have been isolated from aquarium
biofilters and are available as commercial supplements, but recent evidence
suggests that ammonia-oxidizing archaea (AOA) are abundant in aquarium
biofilters. In this study, we report the cultivation and closed genome sequence
of the novel AOA representative "Candidatus Nitrosotenuis aquarius," which was
enriched from a freshwater aquarium biofilter. "Ca Nitrosotenuis aquarius"
oxidizes ammonia stoichiometrically to nitrite with a concomitant increase in
thaumarchaeotal cells and a generation time of 34.9 h. "Ca Nitrosotenuis
aquarius" has an optimal growth temperature of 33 degrees C, tolerates up to 3 mM
NH4Cl, and grows optimally at 0.05% salinity. Transmission electron microscopy
revealed that "Ca Nitrosotenuis aquarius" cells are rod shaped, with a diameter
of ~0.4 MUm and length ranging from 0.6 to 3.6 MUm. In addition, these cells
possess surface layers (S-layers) and multiple proteinaceous appendages.
Phylogenetically, "Ca Nitrosotenuis aquarius" belongs to the group I.1a
Thaumarchaeota, clustering with environmental sequences from freshwater aquarium
biofilters, aquaculture systems, and wastewater treatment plants. The complete
1.70-Mbp genome contains genes involved in ammonia oxidation, bicarbonate
assimilation, flagellum synthesis, chemotaxis, S-layer production, defense, and
protein glycosylation. Incubations with differential inhibitors indicate that "Ca
Nitrosotenuis aquarius"-like AOA contribute to ammonia oxidation within the
aquarium biofilter from which it originated.IMPORTANCE Nitrification is a
critical process for preventing ammonia toxicity in engineered biofilter
environments. This work describes the cultivation and complete genome sequence of
a novel AOA representative enriched from a freshwater aquarium biofilter. In
addition, despite the common belief in the aquarium industry that AOB mediate
ammonia oxidation, the present study suggests an in situ role for "Ca
Nitrosotenuis aquarius"-like AOA in freshwater aquarium biofilters.
PMID- 29959259
TI - Serum glutamine and hospital-acquired infections after aneurysmal subarachnoid
hemorrhage.
AB - OBJECTIVE: To understand nutritional and inflammatory factors contributing to
serum glutamine levels and their relationship to hospital-acquired infections
(HAIs) after aneurysmal subarachnoid hemorrhage (SAH). METHODS: A prospective
observational study of patients with SAH who had measurements of daily caloric
intake and C-reactive protein, transthyretin, tumor necrosis factor alpha
receptor 1a (TNFalphaR1a), glutamine, and nitrogen balance performed within 4
preset time periods during the 14 days after SAH. Factors associated with
glutamine levels and HAIs were analyzed with multivariable regression. HAIs were
tracked daily for time-to-event analyses. Outcome 3 months after SAH was assessed
by the Telephone Interview for Cognitive Status and modified Rankin Scale.
RESULTS: There were 77 patients with an average age of 55 +/- 15 years. HAIs
developed in 18 (23%) on mean SAH day 8 +/- 3. In a multivariable linear
regression model, negative nitrogen balance (p = 0.02) and elevated TNFalphaR1a
(p = 0.04) were independently associated with higher glutamine levels during the
study period. The 14-day mean glutamine levels were lower in patients who
developed HAI (166 +/- 110 vs 236 +/- 81 MUg/mL, p = 0.004). Poor admission Hunt
and Hess grade (p = 0.04) and lower glutamine levels (p = 0.02) predicted time to
first HAI. Low 14-day mean levels of glutamine were associated with a poor
recovery on the Telephone Interview for Cognitive Status score (p = 0.03) and
modified Rankin Scale score (p = 0.04) at 3 months after injury. CONCLUSIONS:
Declining glutamine levels in the first 14 days after SAH are influenced by
inflammation and associated with an increased risk of HAI.
PMID- 29959260
TI - Racial/ethnic variation of APOE alleles for lobar intracerebral hemorrhage.
AB - OBJECTIVE: APOE epsilon2 and epsilon4 alleles have been associated with lobar
intracerebral hemorrhage (ICH) in predominately white populations; we sought to
evaluate whether this held true among black and Hispanic populations. METHODS:
The Ethnic/Racial Variations of Intracerebral Hemorrhage study is a prospective,
multicenter case-control study of ICH among white, black, and Hispanic
participants. Controls were recruited to match cases based on age,
ethnicity/race, sex, and geographic location. APOE genotyping and ICH location
was determined blinded to clinical data. RESULTS: There were 907 cases of lobar
ICH and 2,660 controls with APOE results. Both APOE epsilon2 (odds ratio [OR]
1.5, 95% confidence interval [CI] 1.1-2.0, p = 0.01) and APOE epsilon4 (OR 2.0,
95% CI 1.5-2.6, p < 1 * 10-4) were associated with lobar ICH among white
participants. Among black participants, neither APOE epsilon2 (OR 1.0, 95% CI 0.7
1.5, p = 0.97) nor APOE epsilon4 (OR 1.0, 95% CI 0.7-1.4, p = 0.90) were
independent risk factors for lobar ICH. Similarly, among Hispanic participants,
neither APOE epsilon2 (OR 1.0, 95% CI 0.6-1.8, p = 0.89) nor APOE epsilon4 (OR
1.2, 95% CI 0.8-1.7, p = 0.36) were associated with lobar ICH. Hypertension was a
significant risk factor for lobar ICH in all 3 racial/ethnic groups. CONCLUSION:
In contrast to Caucasian patients, in which amyloid risk factors predominate in
lobar ICH, we found that hypertension was the predominant risk factor for lobar
ICH. While APOE alleles are a risk factor for lobar ICH in white patients, they
appear to have a much lower effect in lobar ICH in African American and Hispanic
American populations. This suggests APOE epsilon2 and APOE epsilon4 do not affect
lobar ICH risk homogeneously across ethnic populations. In addition, hypertension
has a prominent role in lobar ICH risk, particularly among minorities.
PMID- 29959262
TI - Patients' shifting goals for deep brain stimulation and informed consent.
AB - OBJECTIVE: To determine using a repeated-measures, prospective design whether
deep brain stimulation (DBS) results in changes in the importance of symptom and
behavioral goals individually identified by patients with Parkinson disease (PD)
before DBS surgery. METHODS: Fifty-two participants recruited from a consecutive
series completed a semistructured interview soliciting their rank-ordered symptom
and behavioral goals and corresponding visual analog scales measuring perceived
symptom severity and limits to goal attainment. Rank orders were reassessed at 2
times after DBS. Changes in rank order over time were examined with chi2
analyses. The relationships between change in symptom severity/limits to
behavioral goal attainment and change in rank order were examined with mixed
effects linear regression models. RESULTS: Most participants changed the rank
order of their symptom (81%) and behavioral (77%) goals 3 months after DBS
surgery. Change in rank order of symptom goals was significantly related to
change in severity ratings such that improvements in self-reported symptom
severity were associated with reductions in rank. In contrast, no such
relationship was evident for the behavioral goals. CONCLUSION: These data
illustrate how patients' primary goals for DBS shift early in stimulation and
highlight the important differences between symptom and behavioral goals. Changes
in the rank order of symptom goals were related to changes in symptom severity,
whereas subtler shifts in behavioral goals were unrelated to improvements after
DBS. This observation suggests that DBS does not affect goals that may be more
reflective of core personal values. The findings provide empiric data that can
help improve the informed consent process.
PMID- 29959264
TI - EEG findings in CAR T-cell therapy-related encephalopathy.
PMID- 29959263
TI - Neurodegeneration, synaptic dysfunction, and gliosis are phenotypic of Alzheimer
dementia.
AB - OBJECTIVE: To test the hypothesis that cognitively unimpaired individuals with
Alzheimer disease (AD) neuropathology differ from individuals with AD dementia on
biomarkers of neurodegeneration, synaptic dysfunction, and glial activation.
METHODS: In a cross-sectional study, adult participants >70 years old (n = 79,
age 77.1 +/- 5.3 years) underwent comprehensive cognitive evaluation and CSF
collection, which was assayed for markers of amyloid, phosphorylated tau (p-tau),
neurodegeneration (neurofilament light protein [NFL] and total tau), synaptic
dysfunction (neurogranin), and glial activation (chitinase-3-like protein 1 [YKL
40]). Participants were divided into 3 groups based on diagnosis and p-tau/beta
amyloid42 (Abeta42): those with low p-tau/Abeta42 and unimpaired cognition were
classified as controls (n = 25); those with high p-tau/Abeta42 diagnosed with AD
dementia or AD-mild cognitive impairment were classified as AD-Dementia (n = 40);
and those with high p-tau/Abeta42 but unimpaired cognition were classified as
mismatches (n = 14). A similar, secondary analysis was performed with no age
exclusion criteria (n = 411). RESULTS: In both the primary and secondary
analyses, biomarker levels between groups were compared with the use of analysis
of covariance while controlling for age and demographic variables. Despite p
tau/Abeta42 and Abeta42/Abeta40 levels comparable to those of the AD-Dementia
group, mismatches had significantly lower levels of NFL and total tau. While not
significantly lower than the AD-Dementia group on YKL-40 and neurogranin,
mismatches were also not significantly different from controls. CONCLUSIONS:
These results provide evidence that, in the absence of significant
neurodegenerative processes, individuals who harbor AD neuropathology may remain
cognitively unimpaired. This finding provides insight into the biological
processes phenotypic of dementia and supports monitoring multiple biomarkers in
individuals positive for AD neuropathology.
PMID- 29959261
TI - Biallelic SQSTM1 mutations in early-onset, variably progressive
neurodegeneration.
AB - OBJECTIVE: To characterize clinically and molecularly an early-onset, variably
progressive neurodegenerative disorder characterized by a cerebellar syndrome
with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline
affecting 11 individuals from 3 consanguineous families. METHODS: We used whole
exome sequencing (WES) (families 1 and 2) and a combined approach based on
homozygosity mapping and WES (family 3). We performed in vitro studies to explore
the effect of the nontruncating SQSTM1 mutation on protein function and the
effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of
sqstm1 down-modulation on the structural integrity of the cerebellum in vivo
using zebrafish as a model. RESULTS: We identified 3 homozygous inactivating
variants, including a splice site substitution (c.301+2T>A) causing aberrant
transcript processing and accelerated degradation of a resulting protein lacking
exon 2, as well as 2 truncating changes (c.875_876insT and c.934_936delinsTGA).
We show that loss of SQSTM1 causes impaired production of ubiquitin-positive
protein aggregates in response to misfolded protein stress and decelerated
autophagic flux. The consequences of sqstm1 down-modulation on the structural
integrity of the cerebellum in zebrafish documented a variable but reproducible
phenotype characterized by cerebellum anomalies ranging from depletion of axonal
connections to complete atrophy. We provide a detailed clinical characterization
of the disorder; the natural history is reported for 2 siblings who have been
followed up for >20 years. CONCLUSIONS: This study offers an accurate clinical
characterization of this recently recognized neurodegenerative disorder caused by
biallelic inactivating mutations in SQSTM1 and links this phenotype to defective
selective autophagy.
PMID- 29959265
TI - Loss of white matter integrity reflects tau accumulation in Alzheimer disease
defined regions.
AB - OBJECTIVE: White matter (WM) projections were assessed from Alzheimer disease
(AD) gray matter regions associated with beta-amyloid (Abeta), tau, or
neurodegeneration to ascertain relationship between WM structural integrity with
Abeta and/or tau deposition. METHODS: Participants underwent diffusion tensor
imaging (DTI), PET Abeta ([18F]AV-45 [florbetapir]), and PET tau ([18F]AV-1451
[flortaucipir]) imaging. Probabilistic WM summary and individual tracts were
created from either a composite or individual gray matter seed regions derived
from Abeta, tau, and neurodegeneration. Linear regressions were performed for
Abeta, age, tau and WM hyperintensities (WMH) to predict mean diffusivity (MD) or
fractional anisotropy (FA) from the corresponding WM summaries or tracts.
RESULTS: Our cohort was composed of 59 cognitively normal participants and 10
cognitively impaired individuals. Abeta was not associated with DTI metrics in WM
summary or individual tracts. Age and WMH strongly predicted MD and FA in several
WM regions, with tau a significant predictor of MD only in the anterior temporal
WM. CONCLUSION: Tau, not Abeta, was associated with changes in anterior temporal
WM integrity. WMH, a proxy for vascular damage, was strongly associated with
axonal damage, but tau independently contributed to the model, suggesting an
additional degenerative mechanism within tracts projecting from regions
vulnerable to AD pathology. WM decline was associated with early tau
accumulation, and further decline may reflect tau propagation in more advanced
stages of AD.
PMID- 29959266
TI - Effects of deep brain stimulation on rest tremor progression in early stage
Parkinson disease.
AB - OBJECTIVE: To evaluate whether the progression of individual motor features was
influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified
Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout)
was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial
dataset. METHODS: The prospective pilot trial enrolled patients with PD aged 50
75 years, treated with PD medications for 6 months-4 years, and no history of
dyskinesia or other motor fluctuations, who were randomized to receive optimal
drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24
months, all patients stopped all PD therapy for 1 week (medication and
stimulation, if applicable). UPDRS-III "off" item scores were compared between
the ODT and DBS + ODT groups (n = 28); items with significant between-group
differences were analyzed further. RESULTS: UPDRS-III "off" rest tremor score
change from baseline to 24 months was worse in patients receiving ODT vs DBS +
ODT (p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT
both "off" and "on" therapy (p < 0.001, p = 0.003, respectively). More ODT
patients developed new rest tremor in previously unaffected limbs than those
receiving DBS + ODT (p = 0.001). CONCLUSIONS: These results suggest the
possibility that DBS in early PD may slow rest tremor progression. Future
investigation in a larger cohort is needed, and these findings will be tested in
the Food and Drug Administration-approved, phase III, pivotal, multicenter
clinical trial evaluating DBS in early PD. CLASSIFICATION OF EVIDENCE: This study
provides Class II evidence that for patients with early PD, DBS may slow the
progression of rest tremor.
PMID- 29959267
TI - Global Health: Science and Practice ... 5 Years In.
PMID- 29959268
TI - Is It Time to Move Beyond Visual Inspection With Acetic Acid for Cervical Cancer
Screening?
PMID- 29959269
TI - Evidence-Based Programs, Yes-But What About More Program-Based Evidence?
PMID- 29959270
TI - Eliminating Mother-to-Child Transmission of HIV by 2030: 5 Strategies to Ensure
Continued Progress.
PMID- 29959271
TI - Doing What We Do, Better: Improving Our Work Through Systematic Program
Reporting.
PMID- 29959272
TI - Expanding the Single-Visit Approach for Cervical Cancer Prevention: Successes and
Lessons From Burkina Faso.
AB - BACKGROUND: Cervical cancer accounts for 23% of cancer incidence and 22% of
cancer mortality among women in Burkina Faso. These proportions are more than 2
and 5 times higher than those of developed countries, respectively. Before 2010,
cervical cancer prevention (CECAP) services in Burkina Faso were limited to
temporary screening campaigns. PROGRAM DESCRIPTION: Between September 2010 and
August 2014, program implementers collaborated with the Ministry of Health and
professional associations to implement a CECAP program focused on coupling visual
inspection with acetic acid (VIA) for screening with same-day cryotherapy
treatment for eligible women in 14 facilities. Women with larger lesions or
lesions suspect for cancer were referred for loop electrosurgical excision
procedure (LEEP). The program trained providers, raised awareness through demand
generation activities, and strengthened monitoring capacity. METHODS: Data on
program activities, service provision, and programmatic lessons were analyzed.
Three data collection tools, an individual client form, a client registry, and a
monthly summary sheet, were used to track 3 key CECAP service indicators: number
of women screened using VIA, proportion of women who screened VIA positive, and
proportion of women screening VIA positive who received same-day cryotherapy.
RESULTS: Over 4 years, the program screened 13,999 women for cervical cancer
using VIA; 8.9% screened positive; and 65.9% received cryotherapy in a single
visit. The proportion receiving cryotherapy on the same day started at a high of
82% to 93% when services were provided free of charge, but dropped to 51% when a
user fee of $10 was applied to cover the cost of supplies. After reducing the fee
to $4 in November 2012, the proportion increased again to 78%. Implementation
challenges included difficulties tracking referred patients, stock-outs of key
supplies, difficulties with machine maintenance, and prohibitive user fees.
Providers were trained to independently monitor services, identify gaps, and take
corrective actions. CONCLUSIONS: Following dissemination of the results that
demonstrated the acceptability and feasibility of the CECAP program, the Burkina
Faso Ministry of Health included CECAP services in its minimum service delivery
package in 2016. Essential components for such programs include provider training
on VIA, cryotherapy, and LEEP; provider and patient demand generation; local
equipment maintenance; consistent supply stocks; referral system for LEEP; non
prohibitive fees; and a monitoring data collection system.
PMID- 29959273
TI - Increasing Contraceptive Use Among Young Married Couples in Bihar, India:
Evidence From a Decade of Implementation of the PRACHAR Project.
AB - BACKGROUND: Evidence on effective behavior change programming for sexual and
reproductive health among married youth aged 15-24 in developing countries is
lacking. To address this gap, we examined monitoring, evaluation, and special
study data from the Promoting Change in Reproductive Behavior of Adolescents
(PRACHAR) Project, which was implemented between 2001 and 2012 in Bihar, India,
over 3 phases using 2 different implementation models (NGO- and government-led).
METHODS: We conducted a synthesis of evidence from multiple PRACHAR studies to
identify key findings on intervention effectiveness, scalability, and sustained
effects on behaviors. Data were triangulated from quantitative population-based
quasi-experimental evaluations from each project phase; the project's performance
monitoring database; and qualitative studies with beneficiaries. RESULTS:
PRACHAR's original comprehensive NGO-led model, which included behavior change
elements and multiple overlapping communication channels (including home visits
and small-group meetings), increased contraceptive use among young married
couples, and these outcomes were sustained 4-8 years after project interventions
ended. Several program elements were critical to the effectiveness of PRACHAR,
including use of a socioecological intervention model with emphasis on behavior
change efforts; use of a gender-synchronized approach that engages both male and
female partners; and intensity of interventions calibrated to different moments
in the life cycle of adolescents and youth. While the hybrid government-NGO model
of PRACHAR implementation reached greater scale than the original NGO-led model,
comparison of results suggests trade-offs in effectiveness of interventions and
sustained impacts. CONCLUSIONS: A decade of learning from the PRACHAR Project in
Bihar, India, finds that comprehensive programming with gender-synchronized
interventions tailored to specific life stages and aimed at different levels of
the socioecological model can effectively increase contraceptive use among
married young people in a conservative context. Shifting from a more intensive
NGO-led model to less intensive government implementation enhances scalability
but may have diminished impact on reach and long-lasting effectiveness.
PMID- 29959274
TI - Effectiveness of SMS Technology on Timely Community Health Worker Follow-Up for
Childhood Malnutrition: A Retrospective Cohort Study in sub-Saharan Africa.
AB - BACKGROUND: The Millennium Villages Project facilitated technology-based health
interventions in rural under-resourced areas of sub-Saharan Africa. Our study
examined whether data entry using SMS compared with paper forms by community
health workers (CHWs) led to higher proportion of timely follow-up visits for
malnutrition screening in under-5 children in Ghana, Rwanda, Senegal, and Uganda.
METHODS: Children under 5 years were screened for malnutrition every 90 days by
CHWs using mid-upper arm circumference (MUAC) readings. CHWs used either SMS
texts or paper forms to enter MUAC data. Reminder texts were sent at 15 days
before follow-up was needed. Chi-square tests assessed proportion of timely
follow-up visits within 90 days between SMS and paper groups. Logistic regression
analysis was conducted in a step-wise multivariate model. Post-hoc power
calculations were conducted to verify strength of associations. RESULTS: SMS data
entry was associated with a higher proportion of timely malnutrition follow-up
visits compared with paper forms across all sites. The association was strongest
with consistent SMS use over consecutive visits. SMS use at the first of 2
consecutive visits was most effective, highlighting the importance of SMS
reminder alerts. CONCLUSIONS: SMS technology with reminders increased timely CHW
malnutrition screening visits for under-5 children in Ghana, Rwanda, Senegal, and
Uganda, highlighting the importance of such technology for improving health
worker behavior in low-resource settings.
PMID- 29959275
TI - Review of Grain Fortification Legislation, Standards, and Monitoring Documents.
AB - OBJECTIVE: Analyze the content of documents used to guide mandatory fortification
programs for cereal grains. METHODS: Legislation, standards, and monitoring
documents, which are used to mandate, provide specifications for, and confirm
fortification, respectively, were collected from countries with mandatory wheat
flour (n=80), maize flour (n=11), and/or rice (n=6) fortification as of January
31, 2015, yielding 97 possible country-grain combinations (e.g., Philippines
wheat flour, Philippines-rice) for the analysis. After excluding countries with
limited or no documentation, 72 reviews were completed, representing 84 country
grain combinations. Based on best practices, a criteria checklist was created
with 44 items that should be included in fortification documents. Two reviewers
independently scored each available document set for a given country and food
vehicle (a country-grain combination) using the checklist, and then reached
consensus on the scoring. We calculated the percentage of country-grain
combinations containing each checklist item and examined differences in scores by
grain, region, and income level. RESULTS: Of the 72 country-grain combinations,
the majority of documentation came from countries in the Americas (46%) and
Africa (32%), and most were from upper and lower middle-income countries (73%).
The majority of country-grain combinations had documentation stating the food
vehicle(s) to be fortified (97%) and the micronutrients (e.g., iron) (100%),
fortificants (e.g., ferrous fumarate) (88%), and fortification levels required
(96%). Most (78%) stated that labeling is required to indicate a product is
fortified. Many country-grain combinations described systems for external (64%)
monitoring, and stated that industry is required to follow quality
assurance/quality control (64%), though detailed protocols (33%) and roles and
responsibilities (45%) were frequently not described. CONCLUSIONS: Most country
grain combinations have systems in place for internal, external, and import
monitoring. However, documentation of other important items that would influence
product compliance to national standard, such as roles and responsibilities
between agencies, the cost of regulating fortification, and enforcement
strategies, are often lacking. Countries with existing mandatory fortification
can improve upon these items in revisions to their documentation while countries
that are beginning fortification can use the checklist to assist in developing
new policies and programs.
PMID- 29959276
TI - High-Risk Advanced Maternal Age and High Parity Pregnancy: Tackling a Neglected
Need Through Formative Research and Action.
AB - Pregnancy among women of advanced maternal age (those 35 years or older) or among
women of high parity (those having had 5 or more births) is linked to maternal
and infant mortality. Yet little is known about the drivers of these pregnancies
as they are often neglected in existing family planning and reproductive health
programs. To better understand the context in which advanced maternal age and
high parity pregnancies occur and the acceptability of discussing associated
pregnancy risks, the Health Communication Capacity Collaborative (HC3) conducted
formative qualitative research between January and March 2015 on the perception
and determinants of such pregnancies in rural and urban areas of Niger and Togo.
We supplemented this research with secondary analyses of data from Demographic
and Health Surveys and a 2014 Niger survey. Our formative research showed that
urban Togolese participants demonstrated more knowledge about advanced maternal
age and high parity pregnancy risks than did participants in Niger as a whole. We
found that such pregnancies were generally seen as part of reproductive norms in
situations where fertility rates remain exceptionally high, especially in Niger.
Social, gender, and religious norms, including competition between co-wives, also
drove women into high parity and advanced maternal age situations, particularly
in Niger, highlighting the need to bring men and community and religious leaders
into family planning conversations to increase acceptance. The study also
provided important insights needed to address these high-risk pregnancies through
culturally appropriate health communication interventions. A main insight was
that providers often had incomplete information about advanced maternal age and
high parity pregnancies and lacked communication skills, protocols, and tools to
appropriately discuss such pregnancy risks with clients. HC3 used these and
additional findings to create an Implementation Kit (I-Kit) for family planning
and maternal and child health program managers with guidance and tangible tools
to address advanced maternal age and high parity pregnancy through social and
behavior change communication. The I-Kit includes health communication materials
to engage women, men, decision makers, communities, health care providers,
journalists, and others. In 2016 and 2017, one organization each in Niger and
Togo piloted the I-Kit, integrated selected I-Kit tools into their unique
programs, and documented their experiences. Both organizations credited the I-Kit
with expanding the scope of their programs to now address advanced maternal age
and high parity pregnancy and provided concrete suggestions for adapting the
materials according to activity and intended audience.
PMID- 29959277
TI - Monitoring Progress in Equality for the Sustainable Development Goals: A Case
Study of Meeting Demand for Family Planning.
AB - OBJECTIVES: Equality is a central component of the Sustainable Development Goals
(SDGs). We took one SDG indicator and benchmark-percent of family planning demand
met with modern contraceptives, with a benchmark of at least 75% in all countries
as a case study to illuminate recommendations for monitoring equality.
Specifically, we assessed levels, patterns, and trends in disparity by key
background characteristics and identified disparity measures that are
programmatically relevant and easy to interpret. METHODS: Data were from the
Demographic and Health Surveys in 55 countries that have conducted at least 2
surveys since 1990. We calculated absolute difference among subgroups,
disaggregated by age, education, household wealth quintile, urban/rural
residence, subnational region/administrative unit, and marital status. Our unit
of analysis was survey, and we conducted largely descriptive analyses. To
understand trends in disparity, we used a fixed-effect linear regression model to
estimate an annual rate of change in absolute differences. RESULTS: A significant
level of disparity existed across various background characteristics, ranging
from a median difference of 5 percentage points by marital status to 32
percentage points by administrative unit. On average across the study countries,
national level of met demand has increased over time while disparity has declined
in most disaggregates including by education, wealth, residence, and age. We
found statistically significant positive correlations among 4 disparity measures
education, wealth, residence, and administrative unit. Disparities by wealth
quintile were easiest to interpret over time and across countries. CONCLUSIONS:
At the global level, we recommend monitoring disparity in met demand by wealth
quintile, which is strongly correlated with disparity by education, residence,
and region and comparable across countries and over time. For monitoring by
individual countries and for programmatic purposes, we further recommend
monitoring disparity by first-level administrative unit, which can provide direct
programmatic relevance.
PMID- 29959278
TI - Stress effects on FosB and interleukin-8 (IL8)-driven ovarian cancer growth and
metastasis.
PMID- 29959279
TI - Basis of dATP inhibition of RNRs.
AB - Ribonucleotide reductases (RNRs) are essential enzymes producing de novo
deoxynucleotide (dNTP) building blocks for DNA replication and repair and
regulating dNTP pools important for fidelity of these processes. A new study
reveals that the class Ia Escherichia coli RNR is regulated by dATP via
stabilization of an inactive alpha4beta4 quaternary structure, slowing formation
of the active alpha2beta2 structure. The results support the importance of the
regulatory alpha4beta4 complex providing insight in design of experiments to
understand RNR regulation in vivo.
PMID- 29959280
TI - Breakdown of Immune Tolerance in AIRE-Deficient Rats Induces a Severe Autoimmune
Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy-like Autoimmune Disease.
AB - Autoimmune regulator (AIRE) deficiency in humans induces a life-threatening
generalized autoimmune disease called autoimmune polyendocrinopathy-candidiasis
ectodermal dystrophy (APECED), and no curative treatments are available. Several
models of AIRE-deficient mice have been generated, and although they have been
useful in understanding the role of AIRE in central tolerance, they do not
reproduce accurately the APECED symptoms, and thus there is still a need for an
animal model displaying APECED-like disease. We assessed, in this study, the
potential of the rat as an accurate model for APECED. In this study, we
demonstrate that in rat, AIRE is expressed by MHC class II (MCH-II)+ and MHC-II-
medullary thymic epithelial cells in thymus and by CD4int conventional dendritic
cells in periphery. To our knowledge, we generated the first AIRE-deficient rat
model using zinc-finger nucleases and demonstrated that they display several of
the key symptoms of APECED disease, including alopecia, skin depigmentation, and
nail dystrophy, independently of the genetic background. We observed severe
autoimmune lesions in a large spectrum of organs, in particular in the pancreas,
and identified several autoantibodies in organs and cytokines such as type I IFNs
and IL-17 at levels similar to APECED. Finally, we demonstrated a biased Ab
response to IgG1, IgM, and IgA isotypes. Altogether, our data demonstrate that
AIRE-deficient rat is a relevant APECED animal model, opening new opportunity to
test curative therapeutic treatments.
PMID- 29959281
TI - Variation in Genome-Wide NF-kappaB RELA Binding Sites upon Microbial Stimuli and
Identification of a Virus Response Profile.
AB - NF-kappaB transcription factors are master regulators of the innate immune
response. Activated downstream of pathogen recognition receptors, they regulate
the expression of genes to help fight infections as well as recruit the adaptive
immune system. NF-kappaB responds to a wide variety of signals, but the processes
by which stimulus specificity is attained remain unclear. In this article, we
characterized the response of one NF-kappaB member, RELA, to four stimuli
mimicking infection in human nasopharyngeal epithelial cells. Comparing genome
wide RELA binding, we observed stimulus-specific sites, although most sites
overlapped across stimuli. Specifically, the response to poly I:C (mimicking
viral dsRNA and signaling through TLR3) induced a distinct RELA profile, binding
in the vicinity of antiviral genes and correlating with corresponding gene
expression. This group of binding sites was also enriched in IFN regulatory
factor motifs and showed overlapping with IFN regulatory factor binding sites. A
novel NF-kappaB target, OASL, was further validated and showed TLR3-specific
activation. This work showed that some RELA DNA binding sites varied in
activation response following different stimulations and that interaction with
more specialized factors could help achieve this stimulus-specific activity. Our
data provide a genomic view of regulated host response to different pathogen
stimuli.
PMID- 29959283
TI - Fear of Mastectomy Associated with Delayed Breast Cancer Presentation Among
Ghanaian Women.
AB - BACKGROUND: Breast cancer is the leading cause of cancer mortality among women
globally. Most women in Ghana present with advanced stage disease. The aim of
this study is to characterize sociocultural factors associated with delayed
presentation. MATERIALS AND METHODS: Qualitative study (grounded theory, constant
comparative method) using individual in-depth interviews with breast cancer
patients seen at the Korle Bu Teaching Hospital in Accra, Ghana. Interviews were
conducted in English and three local languages. We achieved theoretical
saturation with 31 participants. RESULTS: The mean length of delay reported by
patients was approximately 1 year. Five recurrent themes were related to delayed
presentation: (a) Women with a confirmed breast cancer diagnosis delay treatment
because of the fear of mastectomy due to self and societal stigma; (b) role of
the church as a social support system given the societal stigma associated with
breast cancer; (c) study participants expressed some awareness of breast cancer,
but with varying depths of breast cancer knowledge encompassing both myths and
misconceptions about breast cancer; (d) most patients present late because they
do not associate a "painless" breast lump with possible breast malignancy; and
(e) delayed presentation linked to significant financial burden associated with
breast cancer treatment. CONCLUSION: Despite current efforts to increase breast
cancer awareness, the fear of mastectomy remains one of the main reasons for
delayed presentation. Successful breast cancer education programs will need to be
framed within the broader sociocultural dimensions of femininity that address
some of the stigma associated with mastectomy reported in the Ghanaian context.
IMPLICATIONS FOR PRACTICE: Most women in Ghana present with advanced-stage
disease. The aim of this study was to characterize sociocultural factors
associated with delayed presentation. Although several quantitative studies have
been conducted on delays in presentation in sub-Saharan Africa (SSA), this study
is one of the few to identify fear of mastectomy as a reason for delayed
presentation. Anecdotal data from current clinical experiences in SSA suggest
that this is still an issue that has not been adequately reported and addressed
in most SSA countries. The research results presented here will hopefully guide
health providers and national organizations in designing breast cancer education
programs in Ghana and other parts of SSA.
PMID- 29959282
TI - An important class of intron retention events in human erythroblasts is regulated
by cryptic exons proposed to function as splicing decoys.
AB - During terminal erythropoiesis, the splicing machinery in differentiating
erythroblasts executes a robust intron retention (IR) program that impacts
expression of hundreds of genes. We studied IR mechanisms in the SF3B1 splicing
factor gene, which expresses ~50% of its transcripts in late erythroblasts as a
nuclear isoform that retains intron 4. RNA-seq analysis of nonsense-mediated
decay (NMD)-inhibited cells revealed previously undescribed splice junctions,
rare or not detected in normal cells, that connect constitutive exons 4 and 5 to
highly conserved cryptic cassette exons within the intron. Minigene splicing
reporter assays showed that these cassettes promote IR. Genome-wide analysis of
splice junction reads demonstrated that cryptic noncoding cassettes are much more
common in large (>1 kb) retained introns than they are in small retained introns
or in nonretained introns. Functional assays showed that heterologous cassettes
can promote retention of intron 4 in the SF3B1 splicing reporter. Although many
of these cryptic exons were spliced inefficiently, they exhibited substantial
binding of U2AF1 and U2AF2 adjacent to their splice acceptor sites. We propose
that these exons function as decoys that engage the intron-terminal splice sites,
thereby blocking cross-intron interactions required for excision. Developmental
regulation of decoy function underlies a major component of the erythroblast IR
program.
PMID- 29959284
TI - Developing a Roadmap for Interventional Oncology.
AB - : Interventional oncology uses image-guided procedures to enhance cancer care.
Today, this specialty plays an increasingly critical role in cancer diagnosis
(e.g., biopsy), cancer therapy (e.g., ablation or embolization), and cancer
symptom palliation (e.g., nephrostomies or biliary drainages). Although the
number of procedures and technical capabilities has improved over the last few
years, challenges remain. In this article we discuss the need to advance existing
procedures, develop new ones, and focus on several operational aspects that will
dictate future interventional techniques to enhance cancer care, particularly by
accelerating drug development and improving patient outcomes. IMPLICATIONS FOR
PRACTICE: Interventional oncology is vital for cancer diagnosis, therapy, and
symptom palliation. This report focuses on current interventional procedures and
techniques with a look toward future improvements that will improve cancer care
and patient outcomes.
PMID- 29959285
TI - Training for Medical Oncologists on Shared Decision-Making About Palliative
Chemotherapy: A Randomized Controlled Trial.
AB - BACKGROUND: Systemic treatment for advanced cancer offers uncertain and sometimes
limited benefit, while the burden can be high. This study examines the effect of
shared decision-making (SDM) training for medical oncologists on observed SDM in
standardized patient assessments. MATERIALS AND METHODS: A randomized controlled
trial comparing training with standard practice was conducted. Medical
oncologists and oncologists-in-training (n = 31) participated in a video
recorded, standardized patient assessment at baseline (T0) and after 4 months
(T1, after training). The training was based on a four-stage SDM model and
consisted of a reader, two group sessions (3.5 hours each), a booster session
(1.5 hours), and a consultation card. The primary outcome was observed SDM as
assessed with the Observing Patient Involvement scale (OPTION12) coded by
observers blinded for arm. Secondary outcomes were observed SDM per stage,
communication skills, and oncologists' satisfaction with communication. RESULTS:
The training had a significant and large effect on observed SDM in the simulated
consultations (Cohen's f = 0.62) and improved observed SDM behavior in all four
SDM stages (f = 0.39-0.72). The training improved oncologists' information
provision skills (f = 0.77), skills related to anticipating/responding to
emotions (f = 0.42), and their satisfaction with the consultation (f = 0.53).
CONCLUSION: Training medical oncologists in SDM about palliative systemic
treatment improves their performance in simulated consultations. The next step is
to examine the effect of such training on SDM in clinical practice and on patient
outcomes. IMPLICATIONS FOR PRACTICE: Systemic treatment for advanced cancer
offers uncertain and sometimes limited benefit, while the burden can be high.
Hence, applying the premises of shared decision-making (SDM) is recommended. SDM
is increasingly advocated based on the ethical imperative to provide patient
centered care and the increasing evidence for beneficial patient outcomes. Few
studies examined the effectiveness of SDM training in robust designs. This
randomized controlled trial demonstrated that SDM training (10 hours) improves
oncologists' performance in consultations with standardized patients. The next
step is to examine the effect of training on oncologists' performance and patient
outcomes in clinical practice.
PMID- 29959286
TI - "Mind" in Betel-quid Use and Related Disorders.
AB - Oral squamous cell carcinoma is characterized by a unique predisposing state
called oral potentially malignant disorders (OPMDs). Wide variety of carcinogenic
insult in the form of detrimental habits can contribute to the causation of
variety of OPMDs.1,2.
PMID- 29959287
TI - Effect of Surface Treatments and Adhesive Materials on the Shear Bond Strength of
Artificial Denture Teeth to Denture Base Resins.
AB - AIM: The purpose of the current study was intended to evaluate the effect of
different surface modifications and different adhesive materials on the shear
bond strength of artificial teeth to heat-polymerized and thermoplastic denture
base materials using different repair techniques. MATERIALS AND METHODS: Forty
cross-linked artificial teeth used to construct different types of acrylic based
denture prosthesis were selected to be bonded to two types of denture base
materials, heat-polymerized acrylic resin denture base material, and
thermoplastic acrylic resin denture base material. The specimens were divided
into four subgroups according to the repair technique and adhesive material used.
The base surfaces of all acrylic teeth then were moistened with monomer prior to
bonding to the denture base specimens. Then, the specimens were tested using
Universal Testing Machine for shear bond strength. The results were analyzed by
using two-way analysis of variance (ANOVA) statistical analysis and multiple
comparison tests, alpha <= 0.05. RESULTS: The effect of the types of denture base
materials vs the surface conditioning methods displayed a statistically
significant difference. CONCLUSION: This study concluded that monomer surface
treatment of the bonded surface of artificial denture teeth and the use of
cyanoacrylate adhesive followed by additional microwave polymerization displayed
better shear bond strength when compared with other repair techniques. CLINICAL
SIGNIFICANCE: Artificial teeth debonding from their denture bases is a common
complication in dental practice. The current study evaluates different repairing
techniques. Within the limitation of this study, the use of cyanoacrylate
adhesive in combination with microwave polymerization is one of the best
techniques of repairing denture teeth debonding.
PMID- 29959288
TI - Spectrophotometric Comparison of Effectiveness of Two In-office Bleaching Agents
with/without Light Activation: A Clinical Study.
AB - AIM: The aim of the study is to evaluate the effectiveness of two different in
office bleaching agents, Zoom2 (Z) and Boost (B), regarding color stability 1
week, 2-week, 1-month and 2-month periods after treatment. MATERIALS AND METHODS:
A total of 60 patients each of whom had anterior teeth of shade A3 or darker were
randomly selected from the pool of patients attending the Dental Hospital at the
University of Dammam. For the Z group (n = 30), a light activation unit was used
to activate the bleaching agent. While for group B (n = 30), the whitening gel
was used without light activation. The shades measurements were taken using spec
trophotometer before the treatment, after 1-week, 2-week, 1-month, and 2-month
periods. RESULTS: Analysis of variance repeated-measures (ANOVA) test was applied
to compare the mean effect of color change between the materials on various
follow-up measurements. Wilcoxon signed rank test was applied to compare the mean
effect of color change within the material on various follow-ups. A p-value <=
0.05 was considered statistically significant. At the termination of the study,
the statistical analysis of the data indicated that both products efficiently
lightened the color of the teeth but Z group is more efficient than B group in
different follow-up intervals. CONCLUSION: Both tested whitening systems
demonstrated efficient tooth whitening. Z system is more efficient and stable
than B system at 2 months' interval. CLINICAL SIGNIFICANCE: Zoom2 bleaching
system is more efficient and stable than Boost bleaching system after 2 months'
follow-up.
PMID- 29959289
TI - Assessment of Shear Bond Strength and Marginal Sealing Ability of Pit and Fissure
Sealants: An in vitro Study.
AB - AIM: The aim of the present study was to compare the shear bond strength and
marginal sealing ability of self-adhering flow-able composite and conventional
fissure sealant. MATERIALS AND METHODS: The samples consisted of 30 healthy
premolar teeth which were extracted due to orthodontic reasons and randomly
divided into two groups of 15, i.e., group I (Fissurit F) and group II (Dyad
Flow). Shear bond strength and marginal sealing ability of both the groups were
evaluated in Statistical Package for the Social Sciences (SPSS) version 16.
RESULTS: The mean shear bond strength of Dyad Flow (group II) was found to be 1.4
+/- 0.87 MPa and in Fissurit F (group I), it was 1.3 +/- 1.4 MPa. Differences
between the groups were statistically significant. In group II, 53.3% of
specimens demonstrated score 0; 33.3% showed score 1; and 13.3% showed score 2.
In group I, scores 0 and 1 showed 33.3% of dye penetration respectively. Scores 2
and 3 demonstrated 26.6 and 6.6% of dye penetration respectively. But there was
no significant difference between both the sealant groups. CONCLUSION: The
present study concluded that self-adhering flowable composite was found to have
better shear bond strength and marginal sealing ability than conventional fissure
sealant. CLINICAL SIGNIFICANCE: Self-adhering flowable composite can be
effectively used in pediatric patients in whom isolation is difficult and
exclusion of bonding agent leads to decrease in time consumption.
PMID- 29959290
TI - Effectiveness of the American Board of Orthodontics Discrepancy Index in
predicting Treatment Time.
AB - AIM: This study was aimed to explore the effect of pretreatment severity of
malocclusion on the duration of the treatment using The American Board of
Orthodontics discrepancy index (ABO-DI). MATERIALS AND METHODS: This clinical
retrospective study consisted of orthodontics records of 37 patients who were
treated with comprehensive fixed orthodontic appliance from 2011 to 2013. The
sample of the study was collected so as to exclude, to the maximum possible, the
patient cooperation variability by reviewing all patient chart entries. The DI
measurements were used to gather the information of the pretreatment and relate
it to the time duration of the treatment. Statistical analyses were performed
using the chi-square test and Pearson correlation coefficient. RESULTS: The
average treatment time was 24.5 months. The DI scores mean for class I and II was
14.30 and 20.15 respectively. Age and sex did not significantly influence the
treatment duration (p > 0.05). CONCLUSION: The results of this study showed that
the ABO-DI could be a useful tool to predict orthodontic treatment time. CLINICAL
SIGNIFICANCE: The ABO-DI can significantly aid in orthodontic treatment time
planning.
PMID- 29959291
TI - Evaluation of Total Salivary Secretory Immunoglobulin A and Mi/fans-specific SIgA
among Children having Dissimilar Caries Status.
AB - INTRODUCTION: The occurrence of dental caries has become quite a common
phenomenon nowadays. The varying levels of salivary secretory immunoglobulin A
(SIgA) usually determine the progression of caries. The present study was aimed
to determine the correlation between SIgA and mutans-specific antigen SIgA in
children having different caries status. Scanning electron microscopic analysis
was also completed to correlate the results. MATERIALS AND METHODS: This study
comprised 60 subjects, who were divided into three groups depending on caries
status. In all, saliva was collected to determine the level of SIgA and mutans
specific antigen SIgA using enzyme linked immunosorbent assay (ELISA). The World
Health Organization (WHO) criteria and method were used to evaluate dental
caries. Bradford reagent was used to evaluate the levels of protein in the
antigen. Furthermore, 20 sections of enamel were randomly obtained to estimate
the severity of caries development among groups. RESULTS: Categorical
characteristics among all groups were compared by basic statistical analysis and
Chi-squared test. Mean age (years) was found to be 9.214 +/- 2.28, 9.5 +/- 2.51,
and 10.2 +/- 2.35 in groups I, II, and III respectively. Mutans-specific IgA
level (|jg/mL) was 34.63 +/- 7.46, 28.24 +/- 4.52, and 23.56 +/- 1.62 in groups
I, II, and III respectively. Total SIgA (jg/mL) was 142.53 +/- 22.4, 186.10 +/-
24.70, and 214.8 +/- 27.56 in groups I, II, and III respectively. Caries index
was 6.74 +/- 2.16, 2.32 +/- 0.86, and 0 +/- 0 in groups I, II, and III
respectively. CONCLUSION: Immunoglobulin A is dominantly present in saliva and it
plays a significant role in prevention of dental caries. Hence, dental caries is
more likely to develop in subjects with low level of salivary IgA (high caries
index). CLINICAL SIGNIFICANCE: A low level of IgA may be associated with a high
risk of developing dental caries. This association may possibly be useful in
predicting the future caries status. Accordingly, suitable caries-preventive
measures can be selected and employed.
PMID- 29959292
TI - Comparative Evaluation of Cytotoxicity and Genotoxicity of Two Bioceramic Sealers
on Fibroblast Cell Line: An in vitro Study.
AB - AIM: The purpose of this study was to evaluate and compare the cytotoxicity and
genotoxicity of two bioceramic root canal sealers: EndoSequence BC and iRoot SP
with zinc oxide eugenol sealers on fibroblast cell line. MATERIALS AND METHODS:
The sealers tested were zinc oxide eugenol, EndoSequence BC, and iRoot SP. Each
material was mixed according to the manufacturer's instructions and mounted into
sterile polyethylene color-coded rings, for cytotoxicity and genotoxicity
evaluation. After 48 hours, the set materials were transferred to previously
marked wells and cytotoxicity evaluation to L929 murine fibroblast cells was done
by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The
percentages of viable cells were then calculated and values were statistically
analyzed by Kruskal-Wallis test. The evaluation of genotoxicity of the materials
to L929 murine fibroblast cells was carried out by Comet assay. To quantify
deoxyribonucleic acid (DNA) damage, the following comet parameters were evaluated
in the assay using Comet scoring software: tail length, tail moment, and Olive
moment. The values were statistically analyzed using Kruskal-Wallis test with a
significance value set to p < 0.05. RESULTS: The results of the study showed that
both cytotoxicity and genotoxicity evaluation by MTT assay and Comet assay can be
done on L929 murine fibroblast cell line. Among the three tested materials, zinc
oxide eugenol showed maximum cytotoxicity to the cells (30.64% viable cells),
followed by EndoSequence BC (71.33% viable cells) and iRoot SP (75.11% viable
cells). The evaluation of DNA damage by genotoxicity assessment showed iRoot SP
to be least genotoxic followed closely by EndoSequence BC. Zinc oxide eugenol was
genotoxic and induced more DNA damage on the fibroblast cell line studied. The
statistical analyses for both the assays were nonsignificant. CONCLUSION: All the
three tested sealers showed varying degrees of cytotoxicity and genotoxicity
while using fibro-blast cell line. Zinc oxide eugenol was most toxic in both the
assays and iRoot SP showed least toxicity, followed closely by EndoSequence BC.
PMID- 29959293
TI - Correlation between Cervical Vertebrae Volume Parameter and the Skeletal
Maturation Status.
AB - AIM: Assessing skeletal maturity is a critical factor in orthopedic treatment and
orthognathic surgery. Quantitative methods have been suggested to decide the
skeletal age. This study aims to assess the correlation between the middle
phalanx of the third finger (MP3) method and cervical vertebral volume parameters
(CVVP) in skeletal age determination. MATERIALS AND METHODS: This cross-sectional
study was conducted on 21 boys and 29 girls between the ages of 8 and 16 years,
who were divided into five groups of skeletal maturation: 100 MP3 radiographs and
cone beam computed tomography (CBCT) were obtained and analyzed. Middle phalanx
of the third finger maturation stages were evaluated according to Perinetti
method (stages F-FG-G-H-I). The CVVP was determined on CBCT using Mimics Medical
software. Analysis of variance (ANOVA) and Bonferroni tests were utilized to
investigate the differences in volumetric parameters between MP3 stages. Spearman
correlation coefficient was employed to obtain the correlation between MP3 stages
and the CVVP. RESULTS: The differences in CVVP concentrated between MP3-I stage
and the previous stages, with the highest values those for the 4th vertebra.
Spearman test revealed a significant highest correlation between MP3 stages and
the CVVP in the 4th vertebra; the lowest was in the 2nd, which was higher in the
girls group. CONCLUSION: Strong level of agreement between the two methods was
significant in the 4th vertebra. CLINICAL SIGNIFICANCE: Measurement of volumes of
the 4th CVVP could be used as simple quantitative analysis in clinical practice
to evaluate the maturity in orthodontic patients.
PMID- 29959294
TI - Evaluation of Effect of Connector Designs in Implant Tooth-supported Fixed
Partial Denture: A Two-dimensional Finite Element Analysis.
AB - AIM: The aim of this study was to evaluate the effect of connector designs on
scale and distribution pattern of the stress generated in the supporting bone of
implant tooth-supported three-unit fixed partial denture in distal extension
situation. MATERIALS AND METHODS: Three-unit fixed partial denture geometric
models with implant abutment in second molar, pontic in first molar, and second
premolar as mesial abutment in distal extension situations were evaluated using a
two-dimensional (2D) finite element analysis. Three models were designed and
constructed with mesial and distal rigid connectors, mesial nonrigid connector,
and distal nonrigid connector respectively, using the software ANSYS, version
10.0 (University Intermediate). The models were analyzed to determine the maximum
equivalent von Mises stress at five critical zones (maximum value) under static
axial loading (240 N) after meshing and assigning the material properties.
RESULTS: The maximum stress concentration values at mesial and distal alveolar
crest of the implant-supporting bone were 60.59 and 68.57 MPa, respectively, in
Model No 1. The high equivalent von Mises stress concentration values at the
mesial and distal alveolar crest of the implant-supporting bone were 1.65 and
0.747 MPa with 0.1 mm vertical movement and 7.88 and 9.34 MPa with 0.5 mm
vertical movement of the connector respectively, in Model No 2. The high
equivalent von Mises stress concentration values at mesial and distal alveolar
crest of the implant-supporting bone were 10.45 and 3.43 MPa with 0.1 mm vertical
movement and 4.50 and 5.71 MPa with 0.5 mm vertical movement of the connector
respectively, in Model No 3. CONCLUSION: In the supporting bone around the
implant in Model No 1, the maximum von Mises stress concentrations were displayed
in the crestal zones. In the supporting bone around the implant abutment, the von
Mises stress concentrations were minimal toward the apical third zone in all the
models. The stress concentrations were minimal in the supporting bone around the
implant and the natural tooth in the models with nonrigid connector. CLINICAL
SIGNIFICANCE: When implant is used as distal abutment in three-unit implant tooth
supported fixed partial denture with pontic at first molar in distal extension
situation, it is recommended to place the nonrigid connector in the mesial side
of the distal implant abutment.
PMID- 29959295
TI - Prognostic New Marker (Bone Morphogenetic Protein 7) in Squamous Cell Carcinoma.
AB - AIM: Despite advances in the treatment of oral squamous cell carcinoma (OSCC),
its prognosis is still poor. Therefore, it is important to identify the
prognostic factors. The aim was to investigate the level of bone morphogenetic
protein 7 (BMP7) in SCC of tongue and its relationship with some
clinicopathologic parameters. MATERIALS AND METHODS: In this cross-sectional
study, 128 patients with primary SCC of tongue were evaluated. Data were
extracted and paraffin blocks were retrieved from the archives of Emam Khomeini
Hospital, Tehran, and immunohistochemistry staining was done for the detection of
marker. Data were analyzed using Statistical Package for the Social Sciences
(SPSS) version 16 and through chi-square and logistic regression tests. RESULTS:
The highest level of BMP7 expression was 54% in men (p = 0.044), 70% in the group
aged under 45 years (p = 0.001), 68.2% in patients with lymph node metastasis (p
< 0.001), and 100% in those with poorly differentiated tumors (p < 0.001). In
multivariate analysis, the presence of lymph node metastasis and increased
histopathological grade associated with 5.7 fold and 4.3 fold increase in the
odds ratio (OR) of BMP7 expression respectively. CONCLUSION: Based on the
results, there was a significant relationship between BMP7 expression and poor
cellular differentiation and lymph node metastasis, so this marker could be a new
prognostic marker in oral cancer. CLINICAL SIGNIFICANCE: This new marker could
help clinicians to determine the prognosis of oral cancer, so it has an effect on
optimal treatment.
PMID- 29959296
TI - Evaluation of Antimicrobial Efficacy of Root Canal Sealers against Enterococcus
faecalis: A Comparative Study.
AB - AIM: The study aimed to evaluate the efficacy of root canal sealer's
antimicrobial activity against Enterococcus faecalis. MATERIALS AND METHODS: Root
canal sealers with the brands Endoflas FS, AH Plus, and Tubli-Seal EWT were
selected. Enterococcus faecalis organisms' zone of inhibition was measured. Tukey
post hoc tests and one-way analysis of variance (ANOVA) were used to compare the
data among study groups and within its group. The data were said to be
statistically significant with an established p-value less than 0.05. RESULTS:
The maximum zone of inhibition (23.20 +/- 1.202 mm) was shown by Endoflas FS
sealer; AH Plus and Tubli-Seal showed the inhibition zone of (18.42 +/- 1.023)
and (16.88 +/- 0.962) respectively, following Endoflas FS. The ANOVA test showed
p < 0.0001, which is highly statistically significant. AH Plus and Endoflas FS
showed a statistically significant difference of 0.04 and 0.001 in between
groups, and there was no statistically significant difference in the Tubli-Seal
group from Tukey post hoc test. CONCLUSION: The study showed that Endoflas FS
sealer has a significant antimicrobial effect against E. faecalis. CLINICAL
SIGNIFICANCE: In clinical situation, despite perfect che-momechanical root canal
preparation, persistence of microorganisms may reinfect the root canal.
Therefore, endodontic root canal sealers play a major role in the eradication of
bacteria. The polymicrobial nature of endodontic infection plays a main role
during the usage of endodontic sealer with antimicrobial agents, which in turn
reduces the failure of endodontic treatment.
PMID- 29959297
TI - Comparison of Cuspal Deflection and Microleakage of Premolar Teeth restored with
Three Restorative Materials.
AB - AIM: This study aimed to assess cuspal deflection and micro-leakage of mesio
occluso-distal (MOD) cavities in premolar teeth restored with three different
tooth-colored restorative materials to determine the effect of polymerization
shrinkage stress over time. MATERIALS AND METHODS: The MOD cavities (4 mm depth)
were prepared in 30 sound human maxillary premolars. The teeth were randomly
divided into three groups (n = 10). The teeth were then restored with Filtek P60
(group I), X-tra fil (group II), and Admira Fusion x-tra (group III). Cuspal
deflection was assessed after 5 minutes, 24 hours, 48 hours, and 7 days by
measuring the intercuspal distance. After restoring the teeth, they were
subjected to 1,000 thermal cycles and were then immersed in 2% methylene blue for
24 hours. After vertical section of teeth, they were observed under a
stereomicroscope to assess micro-leakage. Data were analyzed using one-way
analysis of variance (ANOVA) and Tukey's honest significant difference (HSD) post
hoc test. Friedman test was used to compare different time points in each group
and nonparametric Mann-Whitney test was applied to assess microleakage (a <
0.05). RESULTS: The mean cuspal deflection was significantly different in the
three groups (p < 0.001). The highest deflection was noted in Filtek P60 (14.8 +/
1.9) and the lowest was noted in Admira Fusion x-tra (7.4 +/- 1.4 MUm). Cuspal
deflection significantly decreased after 7 days, but did not return to the
baseline value. Admira Fusion x-tra showed significantly less deflection after 7
days (p < 0.001), but the other two groups were the same (p = 0.3). Microleakage
was not significantly different among the three groups (p > 0.05). CONCLUSION:
The lowest cuspal deflection was noted in Admira Fusion x-tra, although marginal
microleakage was not significantly different among the groups. CLINICAL
SIGNIFICANCE: As the lowest cusp deflection was noted in Admira Fusion x-tra,
this restorative material can be suitable for esthetic restoration of extensive
posterior cavities.
PMID- 29959298
TI - Evaluation of the Efficacy of Guava Extract as an Antimicrobial Agent on
Periodontal Pathogens.
AB - AIM: The present study was undertaken to assess the inhibitory effect of guava
extracts on Porphyromonas gingivalis and Aggregatibacteractinomycetemcomitans, to
assess the time-kill curve of P. gingivalis and A. actinomycetemcomitans, and to
determine the antiproteolytic activity of guava on P. gingivalis. MATERIALS AND
METHODS: Kanamycin blood agar was used to isolate P. gingivalis and A.
actinomycetemcomitans. Ethanolic guava extract (EGE) and aqueous guava extract
(AGE) were prepared and the inhibitory effects of these extracts for two
periodontal pathogens were tested by minimum inhibitory concentration (MIC) and
minimum bactericidal concentration (MBC) procedures. Antibacterial activity of
guava extracts was determined by well diffusion method. Antiproteolytic activity
of guava on protease of P. gingivalis was determined by gelatin liquefaction
test. RESULTS: The MIC determined for AGE and EGE was at 75 MUL/mL concentration
for P. gingivalis, whereas EGE exhibited the activity at 75 MUL/mL on P.
gingivalis. The MIC determined for AGE was at 50 MUL/mL for A.
actinomycetemcomitans, whereas MIC determined for EGE was at 3.12 MUL/mL for A.
actinomycetemcomitans. Porphyromonas gingivalis was susceptible to EGE compared
with AGE. Aggregatibacter actinomycetemcomitans was more susceptible to guava
extracts compared with P. gingivalis. CONCLUSION: Guava extract may be a
potential therapeutic agent for periodontitis as it shows significant activity
against both P. gingivalis and A. actinomycetemcomitans. CLINICAL SIGNIFICANCE:
Guava leaves extract can be used as economical and suitable adjuvant to synthetic
drugs and can be a potential therapeutic agent for periodontitis.
PMID- 29959299
TI - Evaluation of Various Sterilization Processes of Orthodontic Instruments using
Biological Indicators and Conventional Swab Test Method: A Comparative Study.
AB - AIM: This study aimed to compare the efficiency of various sterilization
procedures using conventional spore monitoring method, i.e., by using swab test
and biological indicators and to determine the efficiency of cold sterilization
by using Bioclenz-G (2% glutaraldehyde) solution. MATERIALS AND METHODS: Each
group was divided into medium load (containing 15 sets of instruments) and heavy
load (containing 30 sets of instruments). Each group was tested 15 times for
medium and heavy loads. Two groups are swab tested control group and experimental
group with three different methods of sterilization: hot air oven, cold
sterilization, and ethylene dioxide sterilization. RESULTS: Spores were present
in all the groups tested for 10 minutes cycle, in comparison with no spore growth
in any of the groups tested for a 10-hour cycle. CONCLUSION: All methods of
sterilization showed complete sterilization of instruments when monitored with
biological indicators. One group of heavy load in steam autoclave and one group
each of medium load and heavy load in hot air oven sterilizer showed
sterilization failure when monitored with the conventional swab test method.
CLINICAL SIGNIFICANCE: This study proves the efficacy and durability of various
sterilization procedures.
PMID- 29959300
TI - Influence of Three-dimensional Imaging on Implant Treatment Planning: Implant
Diameter and Length.
AB - AIM: To investigate the influence of the radiographic modalities panoramic
radiography (PR) and cone beam computed tomography (CBCT) on selection of implant
length and diameter. MATERIALS AND METHODS: Potential implant sites (59 sites, 40
patients) with available PRs and CBCTs were selected from the databases of two
University dental schools. Six experienced clinicians were asked to select the
appropriate implant length and diameter based on PR and CBCT. Results were
compared with the actual surgical procedure and intra- /interrater agreement was
calculated using Cohen's kappa. RESULTS: On average, greater implant length was
more often planned based on PR (24.2 vs 8.8% with CBCT), while wider implants
were generally more frequently planned based on CBCTs (19.9 vs 29.7% with PR).
Implant treatment planning based on PR and on CBCT images was equal in 50 to 67%.
Compared with the actual surgery, CBCT revealed a higher agreement (46% for
implant length), while for PR, 34.4% equal implant length was observed.
CONCLUSION: The radiographic modality used for implant treatment planning affects
implant selection. CLINICAL SIGNIFICANCE: The CBCT scans are advantageous for
choosing the appropriate implant dimension. Caution should be exercised when
selecting implant length planned from PR.
PMID- 29959301
TI - Comparative Assessment of Facial Asymmetry in Malocclusion using Posteroanterior
View.
AB - AIM: The study was conducted to assess facial asymmetry in various dental
malocclusions and to determine asymmetry in lower, mid, and upper face and jaws
using posteroanterior cephalometric analysis. MATERIALS AND METHODS: Overall, 120
posteroanterior cepha-lograms were taken of individuals between 12 and 25 years
of both sexes, and were divided into four groups: Angle's class I excellent
occlusion, Angle's class I malocclusion, Angle's class II malocclusion, and
Angle's class III malocclusion. These cepha-lograms were traced and Grummon's
analysis was performed. RESULTS: In Angle's class I occlusion and Angle's class
II malocclusion, the results obtained showed asymmetry present in the upper face.
Correlation was found between occlusion, maloc-clusion, and facial asymmetry.
CONCLUSION: Facial asymmetry was found in all dental occlusions whether excellent
or malocclusion group, with maximum asymmetry having upward trend toward upper
face starting from lower. CLINICAL SIGNIFICANCE: For the success of the
orthodontic treatments in various types of malocclusion and to determine the
facial asymmetry, posteroanterior view can be very helpful, as it gives
additional information which can be utilized to augment treatment planning and
improve prognosis in terms of relapse prevention.
PMID- 29959302
TI - Assessment of the Effect of Simulated Rhinoplasty and Genioplasty on the Facial
Profile Attractiveness of Patients with a Convex Face.
AB - AIM: This study was performed to evaluate the effect of rhinoplasty and
genioplasty on facial profile attractiveness assessed by orthodontists and
laypersons. MATERIALS AND METHODS: In this study, posttreatment cephalo-grams of
30 class II patients with convex profile and nasal hump who had undergone
camouflage treatment were traced. These profile outlines were modified by
computer software to simulate rhinoplasty and genioplasty. Then, all these
outlines were converted into silhouettes. There were four groups: no
modification, rhinoplasty (R), genioplasty (G), and rhinoplasty plus genioplasty
(RG). Esthetic assessment of all patients was done by two panels: six
orthodontists and six laypersons. Data were analyzed using Friedman's and
Wilcoxon's test with a significance level of 0.05. RESULTS: The highest mean
esthetics scores belonged to RG (3.9 +/- 0.6), followed by R (3.5 +/- 0.5), G
(2.4 +/- 0.5), and the initial image of the patients (2.13 +/- 0.5). There was a
significant improvement following all surgeries as determined by all evaluators
(p < 0.001), except for orthodontists who did not find genioplasty more esthetic
than no modification (p = 0.139). The mean score of esthetics by orthodontists
was more than laypersons in all groups (p > 0.05). CONCLUSION: Both rhinoplasty
and genioplasty improved the attractiveness of the patients' facial profiles. The
greatest improvement in the facial profile attractiveness in convex faces was
observed after simultaneous nasal hump elimination and chin argumentation
procedures. CLINICAL SIGNIFICANCE: Although both rhinoplasty and genioplasty
could improve patients' profile, the best result is achieved when combination of
them is used for treatment of convex facial profile patients.
PMID- 29959303
TI - Evaluation of Effectiveness of Two Different Endodontic Retreatment Systems in
Removal of Gutta-percha: An in vitro Study.
AB - AIM: To determine the effectiveness of two different endodontic retreatment
systems for the removal of laterally compacted gutta-percha (GP). MATERIALS AND
METHODS: Sixty-three freshly extracted human maxillary central incisors were used
for the study. The teeth were instrumented with K-flex files and obturated using
lateral condensation technique with GP and AH Plus sealer. The teeth were divided
into three retreatment groups, each group consisting of 21 teeth. Group I: D-RaCe
desobturation files (D-RaCe); group II: ProTaper Universal retreatment files
(PTUR); group III: Hedstrom files (H-file). After removal of GP, the teeth were
split longitudinally and divided into three equal parts: Cervical, middle, and
apical third. The middle and apical thirds of all root halves were examined using
scanning electron microscope (SEM). The total surface area covered by the
residual debris was evaluated using Motic Image plus 2.0 software. Statistical
analysis was done by one-way analysis of variance (ANOVA) test with a p-value
<0.05 used to determine significance and Tukey's multiple post hoc tests used for
comparison between the groups, and 't' test was done for comparison between the
thirds within the same group. RESULTS: The PTUR retreatment files showed overall
better performance compared with D-RaCe files and H-files. The PTUR files
performed better at middle third compared with others. The PTUR files and D-RaCe
files performed equally at apical third better than H-files. CONCLUSION: ProTaper
retreatment files are better compared with D-RaCe files and H-files for the
retreatment of the previously endodontically treated teeth. CLINICAL
SIGNIFICANCE: Highest efficacy for the removal of GP was shown by ProTaper
Universal System followed by D-RaCe and H-file.
PMID- 29959304
TI - Effect of Henna Addition on the Surface Roughness and Hardness of
Polymethylmethacrylate Denture Base Material: An in vitro Study.
AB - AIM: This study aimed to evaluate the effect of the addition of various henna
which can have antifungal properties-on the surface roughness and hardness of
polymethylmethacrylate (PMMA) denture base material. MATERIALS AND METHODS: A
total of 99 rectangular-shaped (10 * 20 * 3 mm3) specimens were prepared from
heat-cured acrylic resin and divided into one control group without the addition
of henna and five test groups, which were prepared by adding Yamanihenna powder
to polymer at concentrations of 1, 2.5, 5, 7.5, and 10 wt%. The polymer was added
to the monomer, mixed, packed, and processed using the conventional water bath
method. After processing, specimens were finished and polished, then kept in
distilled water for 48 +/- 2 hours. A profilom-eter and Vickers hardness tester
were used to measure surface roughness and hardness respectively. Statistical
data analysis was conducted via Statistical Package for the Social Sciences
(SPSS) version 20.0 (IBM, USA). The independent sample t-test was used and p <=
0.05 was considered statistically significant. RESULTS: The addition of henna at
varying concentrations significantly increased the surface roughness values (p <=
0.01) while decreasing hardness (p <= 0.0001). The most favorable addition value
was 1% henna between all henna groups. CONCLUSION: The addition of henna to the
acrylic resin may negatively affect the surface properties of PMMA acrylic
denture base. CLINICAL SIGNIFICANCE: Antimicrobial denture with minimum
deterioration effects on its physical properties could be achieved with henna
addition to denture base material in low concentration. However, 1% henna showed
the best results between the henna groups as regards roughness and hardness
values.
PMID- 29959305
TI - Comparison of Beta and ANB Angles for Evaluation of Sagittal Skeletal
Discrepancy: A Cephalometric Study.
AB - AIM: Diagnosis in orthodontic cases and treatment planning is a precise
assessment of sagittal jaw relationship. A number of angular and linear
measurements have been used to attain correct diagnosis. The present study is
done to compare beta angle and A point-nasion-B point (ANB) angle for sagittal
skeletal discrepancies. MATERIALS AND METHODS: A total of 105 subjects were
included in between the age group of 18 and 24 years and were categorized based
on the skeletal patterns as class I, class II, and class III having a sample of
35 in each group. Based on the ANB angle and patients' profile, the sample was
divided into different skeletal groups. Beta angle is the angle amid the
perpendicular from C to B line through point A and the A-B line. Analysis of
variance (ANOVA) and post hoc Scheffe's test were applied to analyze dependent
variables. The level of significance was set at p-value 0.05. RESULTS: The mean
scores of ANB for class I skeletal pattern were 2.46 +/- 0.460, for class II,
5.64 +/- 1.258, and for class III, -1.03 +/- 1.618. Similarly, significant
differences were observed in beta angle for class I skeletal pattern as 31.71 +/-
3.885, for class II, 24.97 +/- 2.162, and for class III, 39.26 +/- 3.649.
CONCLUSION: Both ANB and beta angle showed significant differences with different
skeletal patterns. CLINICAL SIGNIFICANCE: Both ANB and beta angle are awfully
supportive diagnostic measurements to scrutinize sagittal jaw relationship.
PMID- 29959306
TI - Comparative Study of the Efficacy of 4% Articaine vs 2% Lidocaine in Surgical
Removal of Bilaterally Impacted Mandibular Third Molars.
AB - AIM: The aim of this study was to evaluate the safety and efficacy of 4%
articaine with epinephrine (1:200,000) vs 2% lidocaine with epinephrine
(1:200,000) during surgical removal of impacted mandibular third molars.
MATERIALS AND METHODS: The present study was undertaken in 20 patients belonging
to American Society of Anesthesiologists (ASA) class I, of the age group between
18 and 30 years with bilaterally impacted mandibular third molars. Each patient
underwent similar surgical procedure. In the first appointment, the patient was
randomly selected to receive either 4% articaine or 2% lidocaine (both with
epinephrine 1:200,000). Intraoperative and postoperative evaluation was done for
both the anesthetic solutions. Following parameters were evaluated: total volume
of anesthetic solution used during the surgery, onset of action of the anesthetic
agent, duration of anesthesia, duration of postoperative analgesia, incidence,
type and severity of adverse reactions, any need to reanesthetize the surgical
zone and quality of anesthesia provided by the local anesthetic. Subjective pain
evaluation was done with the aid of 100 mm length visual analog scale (VAS) both
intraoperatively and postoperatively. RESULTS: In the present study, 4% articaine
was found to have a significantly shorter onset of action than 2% lidocaine.
Duration of anesthesia and postoperative analgesia of 4% articaine with
epinephrine 1:200,000 was found to be significantly (1.44 and 1.28 times
respectively) longer than 2% lidocaine with epinephrine 1:200,000. But no
significant difference was found in other parameters. CONCLUSION: 4% articaine in
comparison with 2% lidocaine (both with epinephrine 1:200,000) provided a shorter
onset of action and longer duration of anesthesia. CLINICAL SIGNIFICANCE: No
significant difference was recorded in the anesthetic efficacy between the two
solutions.
PMID- 29959307
TI - Veneer or Interproximal Enamel Reduction?
AB - BACKGROUND: Clinicians often ask, "Veneer or no to veneer?" Clinicians usually
think of porcelain veneers for cases in which patients are dissatisfied with
their teeth shape. Interproximal reduction can change teeth's shape and
appearance within the enamel to improve gingival contour, eliminate black
gingival triangles, and correct the Curve of Spee. AIM: Our aim is to present to
clinicians the option of reshaping and interproximal reduction (IPR) as a valid
alternative to porcelain veneers. CASE REPORT: A male patient with round bulbous
shaped anterior maxillary teeth sought a better masculine smile. Interproximal
reduction with thin bur size was performed to reshape the anterior teeth in order
to achieve a proportional teeth width to height and give a more rectangular
rather than square shape. Finally, the orthodontist closed the multiple diastemas
using round wires in order to reduce anterior teeth proclination. The patient
received bleaching treatment and minor composite fillings. CONCLUSION: Not every
cosmetic case should be treated with veneers and crowns. Conservative minimal
intervention, such as IPR was more than sufficient in treating such cases. It is
the right of the patients to be informed and educated about all possible
treatment options. CLINICAL SIGNIFICANCE: Minor reshaping and IPR preserving
teeth structures can be helpful in achieving esthetic results and patients'
confidence.
PMID- 29959308
TI - A Case of Live Donor Liver Transplantation in Acute-on-Chronic Liver Failure with
Budd-Chiari Syndrome: Donor and Recipient with Antiphospholipid Antibody
Syndrome.
AB - BACKGROUND Acute-on-chronic liver failure was first defined within the last 10
years as acute decompensation of chronic liver disease accompanied by multiorgan
failure and poor outcome. Budd-Chiari syndrome is a rare and potentially deadly
hepatic condition. To the best of our knowledge, this is the first case report of
a live liver donor recipient with antiphospholipid antibody syndrome. CASE REPORT
A 47-year-old woman from Sudan with acute-on-chronic liver failure and subacute
Budd-Chiari syndrome triggered by active pneumonia was evacuated to Amman,
Jordan. In Amman, she was transferred to our hospital for liver transplant
evaluation. She presented with progressive liver failure, acute kidney failure,
acute respiratory failure, and encephalopathy stage IV. Multidisciplinary therapy
was initiated with IV anti-infective drugs and optimizing mechanical ventilation.
Clinically, we stopped her progressive deterioration after 48 h and she improved
slightly in our ICU. Accelerated work-up for donors and recipient was completed
and her daughter was selected as a medically appropriate donor despite the fact
that she was found to have heterozygote factor V Leiden mutation and
antiphospholipid antibody syndrome, similar to her mother. A lifesaving live
donor liver transplantation was carried out after 72 h. Donor and recipient were
discharged in good condition with normal liver function and both were discharged
on anticoagulant Rivaroxaban 20 mg. CONCLUSIONS We present the first case of a
patient with acute-on-chronic liver failure with subacute Budd-Chiari syndrome,
which was triggered by bacterial pneumonia and was successfully treated by live
donor liver transplantation from a donor with antiphospholipid antibody syndrome.
PMID- 29959309
TI - Comparison of Spinal Curvatures in the Sagittal Plane, as Well as Body Height and
Mass in Polish Children and Adolescents Examined in the Late 1950s and in the
Early 2000s.
AB - BACKGROUND Humans are exposed to various stimuli which lead to somatic
modifications and changes in body posture, negatively affecting many of its
characteristics. The purpose of this study was to assess significant alterations
which occurred in selected morphological features and spinal curvatures in
children and adolescents over a period of 40 years. MATERIAL AND METHODS The
total of 7041 subjects, aged 4-18 years (mean age 11.3 years) were included in
the study, which was designed to compare measurements performed in year 1959
(Group 1, n=3235 individuals) and in year 2003 (Group 2, n=3806 individuals). The
children were examined for body height, body mass, as well as thoracic and lumbar
curvatures. In 1959, the measurements were carried out using a spherodorsimeter,
while in 2003, the CQ System photogrammetry was used, producing corresponding
results. The Mann-Whitney U test and the Student's t-test were used for
statistical analysis. RESULTS The findings showed a significant decrease in the
angle of lumbar lordosis and in sacral inclination as well as an increase in body
height and mass, particularly in prepubertal children. On the other hand, the
angle of thoracic kyphosis and the partial angles of physiological spinal
curvatures changed only to a small degree over the 40-year period. CONCLUSIONS
This study provides evidence related to changes which occurred during the
relevant period of over 40 years, namely a decrease in both the angle of lumbar
lordosis and the sacral inclination angle, as well as an increase in body height
and mass. These changes should be taken into consideration in selecting norms and
standards applied in healthcare services, and the findings suggest it is
necessary to regularly update such standards.
PMID- 29959310
TI - Prophylactic Atrial Fibrillation Ablation in Atrial Flutter Patients without
Atrial Fibrillation: A Meta-Analysis with Trial Sequential Analysis.
AB - BACKGROUND New-onset atrial fibrillation (AF) is common after atrial flutter
(AFL) ablation, but it was unclear whether AF ablation could reduce the incidence
of AF in AFL patients without AF history. The present meta-analysis was conducted
to evaluate the benefit of prophylactic AF ablation in reducing the occurrence of
AF in typical AFL patients. MATERIAL AND METHODS We systematically searched
PubMed, EMBASE, and the Cochrane Library from inception to December 2017 for
randomized controlled trials (RCTs) that assessed the efficacy of AF ablation in
reducing the occurrence of AF in AFL patients without AF. Trial sequential
analysis (TSA) was used to control random errors and calculate the required
information size. RESULTS Four trials (n=357 patients) met the inclusion criteria
and were included in our meta-analysis. The incidence of AF after AFL ablation
was 46.4%. We observed that prophylactic AF ablation reduced the AF incidence
compared with simple AFL ablation (26.1% versus 46.4%, RR: 0.57, 95% CIs: 0.42
0.76, P=0.0002) with a prolonged procedure duration (P<0.00001) and fluoroscopy
time (P=0.004). Further TSA indicated that more RCTs were needed to reach more
conclusive results. There was no significant difference in clinical complications
(P=0.33) between the 2 groups. CONCLUSIONS This meta-analysis provides evidence
that prophylactic AF ablation may be more effective than simple AFL ablation in
reducing AF incidence after AFL ablation. Large prospective RCTs are warranted to
confirm the benefit of prophylactic AF ablation in AFL patients without AF
history.
PMID- 29959311
TI - Resveratrol enhances the functionality and improves the regeneration of
mesenchymal stem cell aggregates.
AB - Mesenchymal stem cell (MSC)-based regeneration, specifically cell aggregate or
cell sheet engineering, is a promising approach for tissue reconstruction.
Considering the advantages of ease of harvest and lack of immune rejection, the
application of autologous MSCs (i.e., patients' own MSCs) in regenerative
medicine has developed considerable interest. However, the impaired cell
viability and regenerative potential following MSCs impacted by disease remain a
major challenge. Resveratrol (RSV) exhibits reliable and extensive rejuvenative
activities that have received increasing clinical attention. Here, we uncovered
that resveratrol enhances the functionality and improves the regeneration of
mesenchymal stem cell aggregates. Periodontal ligament MSCs (PDLSCs) from normal
control subjects (N-PDLSCs) and periodontitis patients (P-PDLSCs) were
investigated. Compared to N-PDLSCs, P-PDLSCs were less capable of forming cell
aggregates, and P-PDLSC aggregates showed impaired osteogenesis and regeneration.
These functional declines could be mimicked in N-PDLSCs by tumor necrosis factor
alpha (TNF-alpha) treatment. Notably, a TNF-alpha-induced functional decline in N
PDLSC aggregates was rescued by RSV application. More importantly, in both N
PDLSCs and P-PDLSCs, RSV promoted cell aggregate formation and improved their
osteogenic potential. Furthermore, as proven ectopically in vivo, the tissue
regenerative capability of P-PDLSC aggregates was also enhanced after RSV
treatment during aggregate formation in vitro. Finally, in a rat in situ
regeneration model, we successfully applied both N-PDLSC aggregates and P-PDLSC
aggregates to repair periodontal defects upon long-term functional improvements
by RSV preconditioning. Together, our data unravel a novel methodology for using
pharmacology (i.e., RSV)-based cell aggregate engineering to improve the
functionality and facilitate the regeneration of MSCs from both healthy and
inflammatory microenvironments, shedding light on improving the application of
autologous MSC-mediated regenerative medicine.
PMID- 29959312
TI - Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity.
AB - Oridonin (Ori) is the major active ingredient of the traditional Chinese
medicinal herb Rabdosia rubescens and has anti-inflammatory activity, but the
target of Ori remains unknown. NLRP3 is a central component of NLRP3 inflammasome
and has been involved in a wide variety of chronic inflammation-driven human
diseases. Here, we show that Ori is a specific and covalent inhibitor for NLRP3
inflammasome. Ori forms a covalent bond with the cysteine 279 of NLRP3 in NACHT
domain to block the interaction between NLRP3 and NEK7, thereby inhibiting NLRP3
inflammasome assembly and activation. Importantly, Ori has both preventive or
therapeutic effects on mouse models of peritonitis, gouty arthritis and type 2
diabetes, via inhibition of NLRP3 activation. Our results thus identify NLRP3 as
the direct target of Ori for mediating Ori's anti-inflammatory activity. Ori
could serve as a lead for developing new therapeutics against NLRP3-driven
diseases.
PMID- 29959313
TI - Surface ocean pH variations since 1689 CE and recent ocean acidification in the
tropical South Pacific.
AB - Increasing atmospheric CO2 from man-made climate change is reducing surface ocean
pH. Due to limited instrumental measurements and historical pH records in the
world's oceans, seawater pH variability at the decadal and centennial scale
remains largely unknown and requires documentation. Here we present evidence of
striking secular trends of decreasing pH since the late nineteenth century with
pronounced interannual to decadal-interdecadal pH variability in the South
Pacific Ocean from 1689 to 2011 CE. High-amplitude oceanic pH changes, likely
related to atmospheric CO2 uptake and seawater dissolved inorganic carbon
fluctuations, reveal a coupled relationship to sea surface temperature variations
and highlight the marked influence of El Nino/Southern Oscillation and
Interdecadal Pacific Oscillation. We suggest changing surface winds strength and
zonal advection processes as the main drivers responsible for regional pH
variability up to 1881 CE, followed by the prominent role of anthropogenic CO2 in
accelerating the process of ocean acidification.
PMID- 29959314
TI - Continuous biomarker monitoring by particle mobility sensing with single molecule
resolution.
AB - Healthcare is in demand of technologies for real-time sensing in order to
continuously guard the state of patients. Here we present biomarker-monitoring
based on the sensing of particle mobility, a concept wherein particles are
coupled to a substrate via a flexible molecular tether, with both the particles
and substrate provided with affinity molecules for effectuating specific and
reversible interactions. Single-molecular binding and unbinding events modulate
the Brownian particle motion and the state changes are recorded using optical
scattering microscopy. The technology is demonstrated with DNA and protein as
model biomarkers, in buffer and in blood plasma, showing sensitivity to picomolar
and nanomolar concentrations. The sensing principle is direct and self-contained,
without consuming or producing any reactants. With its basis in reversible
interactions and single-molecule resolution, we envisage that the presented
technology will enable biosensors for continuous biomarker monitoring with high
sensitivity, specificity, and accuracy.
PMID- 29959315
TI - Auditory cortical activity drives feedback-dependent vocal control in marmosets.
AB - Vocal communication is a sensory-motor process requiring auditory self-monitoring
to correct errors and to ensure accurate vocal production. When presented with
altered speech feedback, humans rapidly change their speech to compensate.
Although previous evidence has demonstrated suppression of auditory cortex during
both speech and animal vocalization, the specific role of auditory cortex in such
feedback-dependent control is unknown. Here we show the relationship between
neural activity in the auditory cortex and feedback-dependent vocal control in
marmoset monkeys. We demonstrate that marmosets, like humans, exhibit feedback
control of vocal acoustics. We further show that feedback-sensitive activity of
auditory cortex neurons predict such compensatory vocal changes. Finally, we
demonstrate that electrical microstimulation of auditory cortex rapidly evokes
similar changes in vocal production. These results are evidence for a causal role
of auditory cortex in vocal self-monitoring and feedback-dependent control, and
have implications for understanding human speech motor control.
PMID- 29959316
TI - Reply to 'Misestimation of heritability and prediction accuracy of male-pattern
baldness'.
PMID- 29959318
TI - Clustering huge protein sequence sets in linear time.
AB - Metagenomic datasets contain billions of protein sequences that could greatly
enhance large-scale functional annotation and structure prediction. Utilizing
this enormous resource would require reducing its redundancy by similarity
clustering. However, clustering hundreds of millions of sequences is impractical
using current algorithms because their runtimes scale as the input set size N
times the number of clusters K, which is typically of similar order as N,
resulting in runtimes that increase almost quadratically with N. We developed
Linclust, the first clustering algorithm whose runtime scales as N, independent
of K. It can also cluster datasets several times larger than the available main
memory. We cluster 1.6 billion metagenomic sequence fragments in 10 h on a single
server to 50% sequence identity, >1000 times faster than has been possible
before. Linclust will help to unlock the great wealth contained in metagenomic
and genomic sequence databases.
PMID- 29959317
TI - Targeted deletion of the AAA-ATPase Ruvbl1 in mice disrupts ciliary integrity and
causes renal disease and hydrocephalus.
AB - Ciliopathies comprise a large number of hereditary human diseases and syndromes
caused by mutations resulting in dysfunction of either primary or motile cilia.
Both types of cilia share a similar architecture. While primary cilia are present
on most cell types, expression of motile cilia is limited to specialized tissues
utilizing ciliary motility. We characterized protein complexes of ciliopathy
proteins and identified the conserved AAA-ATPase Ruvbl1 as a common novel
component. Here, we demonstrate that Ruvbl1 is crucial for the development and
maintenance of renal tubular epithelium in mice: both constitutive and inducible
deletion in tubular epithelial cells result in renal failure with tubular
dilatations and fewer ciliated cells. Moreover, inducible deletion of Ruvbl1 in
cells carrying motile cilia results in hydrocephalus, suggesting functional
relevance in both primary and motile cilia. Cilia of Ruvbl1-negative cells lack
crucial proteins, consistent with the concept of Ruvbl1-dependent cytoplasmic pre
assembly of ciliary protein complexes.
PMID- 29959319
TI - Xapuri virus, a novel mammarenavirus: natural reassortment and increased
diversity between New World viruses.
AB - Mammarenavirus RNA was detected in Musser's bristly mouse (Neacomys musseri) from
the Amazon region, and this detection indicated that rodents were infected with a
novel mammarenavirus, with the proposed name Xapuri virus (XAPV), which is
phylogenetically related to New World Clade B and Clade C viruses. XAPV may
represent the first natural reassortment of the Arenaviridae family and a new
unrecognized clade within the Tacaribe serocomplex group.
PMID- 29959320
TI - Author Correction: GWAS for male-pattern baldness identifies 71 susceptibility
loci explaining 38% of the risk.
AB - We have been alerted that in our recent Article the calculations used to
transform the heritability from the observed scale to the liability scale did not
take into account the individuals in category 2 of the baldness scale, who were
removed in our original analysis. This led to an overestimation of the
heritability on the liability scale, which should have been 0.62 instead of 0.94.
Moreover, in the Title and in the Abstract, we report that we can explain 38% of
the risk, while in fact that is the proportion of heritability explained by the
loci we discovered. These errors do not substantially change the paper or its
conclusions apart from the statement MBP is therefore probably one of the most
heritable complex traits. Genome-wide significant associations and pathway
analyses are not affected in any way and male-pattern baldness remains less
genetically complex than other complex traits. We wish to thank Yap et al. for
bringing this to our attention.
PMID- 29959321
TI - Targeting EZH2 reactivates a breast cancer subtype-specific anti-metastatic
transcriptional program.
AB - Emerging evidence has illustrated the importance of epigenomic reprogramming in
cancer, with altered post-translational modifications of histones contributing to
pathogenesis. However, the contributions of histone modifiers to breast cancer
progression are unclear, and how these processes vary between molecular subtypes
has yet to be adequately addressed. Here we report that genetic or
pharmacological targeting of the epigenetic modifier Ezh2 dramatically hinders
metastatic behaviour in both a mouse model of breast cancer and patient-derived
xenografts reflective of the Luminal B subtype. We further define a subtype
specific molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression
of the FOXC1 gene, thereby inactivating a FOXC1-driven, anti-invasive
transcriptional program. We demonstrate that higher FOXC1 is predictive of
favourable outcome specifically in Luminal B breast cancer patients and establish
the use of EZH2 methyltransferase inhibitors as a viable strategy to block
metastasis in Luminal B breast cancer, where options for targeted therapy are
limited.
PMID- 29959323
TI - Prioritizing network communities.
AB - Uncovering modular structure in networks is fundamental for systems in biology,
physics, and engineering. Community detection identifies candidate modules as
hypotheses, which then need to be validated through experiments, such as
mutagenesis in a biological laboratory. Only a few communities can typically be
validated, and it is thus important to prioritize which communities to select for
downstream experimentation. Here we develop CRANK, a mathematically principled
approach for prioritizing network communities. CRANK efficiently evaluates
robustness and magnitude of structural features of each community and then
combines these features into the community prioritization. CRANK can be used with
any community detection method. It needs only information provided by the network
structure and does not require any additional metadata or labels. However, when
available, CRANK can incorporate domain-specific information to further boost
performance. Experiments on many large networks show that CRANK effectively
prioritizes communities, yielding a nearly 50-fold improvement in community
prioritization.
PMID- 29959322
TI - Pervasive genetic interactions modulate neurodevelopmental defects of the autism
associated 16p11.2 deletion in Drosophila melanogaster.
AB - As opposed to syndromic CNVs caused by single genes, extensive phenotypic
heterogeneity in variably-expressive CNVs complicates disease gene discovery and
functional evaluation. Here, we propose a complex interaction model for
pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact
with each other in conserved pathways to modulate expression of the phenotype.
Using multiple quantitative methods in Drosophila RNAi lines, we identify a range
of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in
different tissues. We test 565 pairwise knockdowns in the developing eye, and
identify 24 interactions between pairs of 16p11.2 homologs and 46 interactions
between 16p11.2 homologs and neurodevelopmental genes that suppress or enhance
cell proliferation phenotypes compared to one-hit knockdowns. These interactions
within cell proliferation pathways are also enriched in a human brain-specific
network, providing translational relevance in humans. Our study indicates a role
for pervasive genetic interactions within CNVs towards cellular and developmental
phenotypes.
PMID- 29959324
TI - Stable complete methane oxidation over palladium based zeolite catalysts.
AB - Increasing the use of natural gas engines is an important step to reduce the
carbon footprint of mobility and power generation sectors. To avoid emissions of
unburnt methane and the associated severe greenhouse effect of lean-burn engines,
the stability of methane oxidation catalysts against steam-induced sintering at
low temperatures (<500 degrees C) needs to be improved. Here we demonstrate how
the combination of catalyst development and improved process control yields a
highly efficient solution for complete methane oxidation. We design a material
based on palladium and hierarchical zeolite with fully sodium-exchanged acid
sites, which improves the support stability and prevents steam-induced palladium
sintering under reaction conditions by confining the metal within the zeolite.
Repeated short reducing pulses enable the use of a highly active transient state
of the catalyst, which in combination with its high stability provides excellent
performance without deactivation for over 90 h in the presence of steam.
PMID- 29959325
TI - High-performance bifunctional porous non-noble metal phosphide catalyst for
overall water splitting.
AB - Water electrolysis is an advanced energy conversion technology to produce
hydrogen as a clean and sustainable chemical fuel, which potentially stores the
abundant but intermittent renewable energy sources scalably. Since the overall
water splitting is an uphill reaction in low efficiency, innovative breakthroughs
are desirable to greatly improve the efficiency by rationally designing non
precious metal-based robust bifunctional catalysts for promoting both the
cathodic hydrogen evolution and anodic oxygen evolution reactions. We report a
hybrid catalyst constructed by iron and dinickel phosphides on nickel foams that
drives both the hydrogen and oxygen evolution reactions well in base, and thus
substantially expedites overall water splitting at 10 mA cm-2 with 1.42 V, which
outperforms the integrated iridium (IV) oxide and platinum couple (1.57 V), and
are among the best activities currently. Especially, it delivers 500 mA cm-2 at
1.72 V without decay even after the durability test for 40 h, providing great
potential for large-scale applications.
PMID- 29959326
TI - One-second coherence for a single electron spin coupled to a multi-qubit nuclear
spin environment.
AB - Single electron spins coupled to multiple nuclear spins provide promising multi
qubit registers for quantum sensing and quantum networks. The obtainable level of
control is determined by how well the electron spin can be selectively coupled
to, and decoupled from, the surrounding nuclear spins. Here we realize a
coherence time exceeding a second for a single nitrogen-vacancy electron spin
through decoupling sequences tailored to its microscopic nuclear-spin
environment. First, we use the electron spin to probe the environment, which is
accurately described by seven individual and six pairs of coupled carbon-13
spins. We develop initialization, control and readout of the carbon-13 pairs in
order to directly reveal their atomic structure. We then exploit this knowledge
to store quantum states in the electron spin for over a second by carefully
avoiding unwanted interactions. These results provide a proof-of-principle for
quantum sensing of complex multi-spin systems and an opportunity for multi-qubit
quantum registers with long coherence times.
PMID- 29959328
TI - Misestimation of heritability and prediction accuracy of male-pattern baldness.
PMID- 29959327
TI - Harnessing synthetic lethality to predict the response to cancer treatment.
AB - While synthetic lethality (SL) holds promise in developing effective cancer
therapies, SL candidates found via experimental screens often have limited
translational value. Here we present a data-driven approach, ISLE (identification
of clinically relevant synthetic lethality), that mines TCGA cohort to identify
the most likely clinically relevant SL interactions (cSLi) from a given candidate
set of lab-screened SLi. We first validate ISLE via a benchmark of large-scale
drug response screens and by predicting drug efficacy in mouse xenograft models.
We then experimentally test a select set of predicted cSLi via new screening
experiments, validating their predicted context-specific sensitivity in hypoxic
vs normoxic conditions and demonstrating cSLi's utility in predicting synergistic
drug combinations. We show that cSLi can successfully predict patients' drug
treatment response and provide patient stratification signatures. ISLE thus
complements existing actionable mutation-based methods for precision cancer
therapy, offering an opportunity to expand its scope to the whole genome.
PMID- 29959329
TI - 2D transition metal dichalcogenides with glucan multivalency for antibody-free
pathogen recognition.
AB - The ability to control the dimensions and properties of nanomaterials is
fundamental to the creation of new functions and improvement of their
performances in the applications of interest. Herein, we report a strategy based
on glucan multivalent interactions for the simultaneous exfoliation and
functionalization of two-dimensional transition metal dichalcogenides (TMDs) in
an aqueous solution. The multivalent hydrogen bonding of dextran with bulk TMDs
(WS2, WSe2, and MoSe2) in liquid exfoliation effectively produces TMD monolayers
with binding multivalency for pathogenic bacteria. Density functional theory
simulation reveals that the multivalent hydrogen bonding between dextran and TMD
monolayers is very strong and thermodynamically favored (DeltaEb = -0.52 eV). The
resulting dextran/TMD hybrids (dex-TMDs) exhibit a stronger affinity (Kd = 11 nM)
to Escherichia coli O157:H7 (E. coli) than E. coli-specific antibodies and
aptamers. The dex-TMDs can effectively detect a single copy of E. coli based on
their Raman signal.
PMID- 29959330
TI - Understanding crystallization pathways leading to manganese oxide polymorph
formation.
AB - Hydrothermal synthesis is challenging in metal oxide systems with diverse
polymorphism, as reaction products are often sensitive to subtle variations in
synthesis parameters. This sensitivity is rooted in the non-equilibrium nature of
low-temperature crystallization, where competition between different metastable
phases can lead to complex multistage crystallization pathways. Here, we propose
an ab initio framework to predict how particle size and solution composition
influence polymorph stability during nucleation and growth. We validate this
framework using in situ X-ray scattering, by monitoring how the hydrothermal
synthesis of MnO2 proceeds through different crystallization pathways under
varying solution potassium ion concentrations ([K+] = 0, 0.2, and 0.33 M). We
find that our computed size-dependent phase diagrams qualitatively capture which
metastable polymorphs appear, the order of their appearance, and their relative
lifetimes. Our combined computational and experimental approach offers a rational
and systematic paradigm for the aqueous synthesis of target metal oxides.
PMID- 29959332
TI - Uhlmann curvature in dissipative phase transitions.
AB - A novel approach based on the Uhlmann curvature is introduced for the
investigation of non-equilibrium steady-state quantum phase transitions (NESS
QPTs). Equilibrium phase transitions fall invariably into two markedly non
overlapping categories: classical phase transitions and quantum phase
transitions. NESS-QPTs offer a unique arena where such a distinction fades off.
We propose a method to reveal and quantitatively assess the quantum character of
such critical phenomena. We apply this tool to a paradigmatic class of lattice
fermion systems with local reservoirs, characterised by Gaussian non-equilibrium
steady states. The relations between the behaviour of the Uhlmann curvature, the
divergence of the correlation length, the character of the criticality and the
dissipative gap are demonstrated. We argue that this tool can shade light upon
the nature of non equilibrium steady state criticality in particular with regard
to the role played by quantum vs classical fluctuations.
PMID- 29959331
TI - The Hsp70 inhibitor 2-phenylethynesulfonamide inhibits replication and
carcinogenicity of Epstein-Barr virus by inhibiting the molecular chaperone
function of Hsp70.
AB - Epstein-Barr virus (EBV) can infect cells in latent and lytic period and cause
serious disease. Epstein-Barr virus nuclear antigen 1 (EBNA1) is essential for
the maintenance of the EBV DNA episome, replication and transcription. 2
phenylethynesulfonamide (PES) is a small molecular inhibitor of Heat shock
protein 70 (Hsp70), which can interact with Hsp70 and disrupts its association
with co-chaperones and substrate proteins of Hsp70. In our study, we found that
PES could decrease the expression of EBNA1, which is independent of effects on
EBNA1 transcription or proteasomal degradation pathway. The central glycine
alanine repeats domain was not required for inhibition of EBNA1 expression by
PES. Also, PES could reduce the amount of intracellular EBV genomic DNA. PES
inhibited proliferation and migration but induced cell cycle arrest and apoptosis
of EBV positive cells. In addition, silencing of Hsp70 decreased expression of
EBNA1 and the amounts of intracellular EBV genomic DNA, and PES increased this
effect on a dose-dependent manner. On the contrast, over-expression of Hsp70
enhanced the expression of EBNA1 and the amounts of intracellular EBV genomic
DNA, but PES inhibited this effect on a dose-dependent manner. Furthermore, Hsp70
interacted with EBNA1 but PES interfered this interaction. Our results indicate
that PES suppresses replication and carcinogenicity of Epstein-Barr virus via
inhibiting the molecular chaperone function of Hsp70.
PMID- 29959333
TI - Costs of injury for scent signalling in a strepsirrhine primate.
AB - Honesty is crucial in animal communication when signallers are conveying
information about their condition. Condition dependence implies a cost to signal
production; yet, evidence of such cost is scarce. We examined the effects of
naturally occurring injury on the quality and salience of olfactory signals in
ring-tailed lemurs (Lemur catta). Over a decade, we collected genital secretions
from 23 (13 male, 10 female) adults across 34 unique injuries, owing primarily to
intra-group fights. Using gas chromatography-mass spectrometry, we tested for
differences in the chemical composition of secretions across pre-injury, injury
and recovery, in animals that did and did not receive antibiotics. Lemur genital
secretions were significantly dampened and altered during injury, with patterns
of change varying by sex, season and antibiotics. Using behavioural bioassays
(excluding odorants from antibiotic-treated animals), we showed that male
'recipients' discriminated injury status based on scent alone, directing more
competitive counter marking towards odorants from injured vs. uninjured male
'signallers.' That injured animals could not maintain their normal signatures
provides rare evidence of the energetic cost to signal production. That
conspecifics detected olfactory-encoded 'weakness' suggests added behavioural
costs: By influencing the likelihood of intra- or inter-sexual conflict,
condition-dependent signals could have important implications for socio
reproductive behaviour.
PMID- 29959334
TI - Home Use of a Neural-connected Sensory Prosthesis Provides the Functional and
Psychosocial Experience of Having a Hand Again.
AB - The loss of a hand has many psychosocial repercussions. While advanced multi
articulated prostheses can improve function, without sensation, they cannot
restore the full experience and connection of a hand. Direct nerve interfaces can
restore naturalistic sensation to amputees. Our sensory restoration system
produced tactile and proprioceptive sensations on the hand via neural stimulation
through chronically implanted electrodes. In this study, upper limb amputees used
a sensory-enabled prosthesis in their homes and communities, autonomously and
unconstrained to specific tasks. These real-life conditions enabled us to study
the impact of sensation on prosthetic usage, functional performance, and
psychosocial experience. We found that sensory feedback fundamentally altered the
way participants used their prosthesis, transforming it from a sporadically-used
tool into a readily and frequently-used hand. Functional performance with
sensation improved following extended daily use. Restored sensation improved a
wide range of psychosocial factors, including self-efficacy, prosthetic
embodiment, self-image, social interaction, and quality of life. This study
demonstrates that daily use of a sensory-enabled prosthesis restores the holistic
experience of having a hand and more fully reconnects amputees with the world.
PMID- 29959335
TI - Synergistic interaction of sprouting and intussusceptive angiogenesis during
zebrafish caudal vein plexus development.
AB - Intussusceptive angiogenesis (IA) is a complementary method to sprouting
angiogenesis (SA). The hallmark of IA is formation of trans-capillary tissue
pillars, their fusion and remodeling of the vascular plexus. In this study, we
investigate the formation of the zebrafish caudal vein plexus (CVP) in
Tg(fli1a:eGFP) y7 and the synergistic interaction of IA and SA in crafting the
archetypical angio-architecture of the CVP. Dynamic in vivo observations and
quantitative analyses revealed that the primitive CVP during development was
initiated through SA. Further vascular growth and remodeling occurred by IA.
Intussusception contributed to the expansion of the CVP by formation of new
pillars. Those pillars arose in front of the already existing ones; and in a
subsequent step the serried pillars elongated and fused together. This resulted
in segregation of larger vascular segments and remodelling of the disorganized
vascular meshwork into hierarchical tree-like arrangement. Blood flow was the
main driving force for IA, particularly shear stress geometry at the site of
pillar formation and fusion. Computational simulations based on hemodynamics
showed drop in shear stress levels at locations of new pillar formation, pillar
elongation and fusion. Correlative 3D serial block face scanning electron
microscopy confirmed the morphological substrate of the phenomena of the pillar
formation observed in vivo. The data obtained demonstrates that after the
sprouting phase and formation of the primitive capillary meshwork, the
hemodynamic conditions enhance intussusceptive segregation of hierarchical
vascular tree i.e. intussusceptive arborization resulting in complex vascular
structures with specific angio-architecture.
PMID- 29959336
TI - Mapping of brain tissue hematocrit in glioma and acute stroke using a dual
autoradiography approach.
AB - Hematocrit (Hct) determines the ability of blood to carry oxygen. While changes
in systemic Hct are known to impact stroke or tumor control, changes in local
(tissue) Hct (tHct) induced by these diseases have however received little
attention. In this study, we evaluate tHct in acute stroke and in glioma models
using a new approach to map tHct across the brain, a dual isotope
autoradiography, based on injections of 125I-labeled albumin and 99mTc-lalbeled
red blood cells in the same animal. For validation purpose, tHct was mapped in
the rat brain (i) under physiological conditions, (ii) following erythropoietin
injection, and (iii) following hemodilution. Then, tHct was then mapped in stroke
(middle cerebral artery occlusion) and tumor models (9LGS and C6). The mean tHct
values observed in healthy brains (tHct = 29 +/- 1.3%), were modified as expected
by erythropoietin (tHct = 36.7 +/- 2.6%) and hemodilution (tHct = 24.2 +/- 2.4%).
Using the proposed method, we observed a local reduction, spatially
heterogeneous, in tHct following acute stroke (tHct = 19.5 +/- 2.5%) and in both
glioma models (9LGS: tHct = 18.5 +/- 2.3%, C6: tHct = 16.1 +/- 1.2%). This
reduction and this heterogeneity in tHct observed in stroke and glioma raises
methodological issues in perfusion imaging techniques where tHct is generally
overlooked and could impact therapeutic strategies.
PMID- 29959337
TI - Hypothesis on monochromatic vision in scorpionflies questioned by new
transcriptomic data.
AB - In the scorpionfly Panorpa, a recent study suggested monochromatic vision due to
evidence of only a single opsin found in transcriptome data. To reconsider this
hypothesis, the present study investigates opsin expression using transcriptome
data of 21 species including representatives of all major lineages of
scorpionflies (Mecoptera) and of three families of their closest relatives, the
fleas (Siphonaptera). In most mecopteran species investigated, transcripts encode
two opsins with predicted peak absorbances in the green, two in the blue, and one
in the ultraviolet spectral region. Only in groups with reduced or absent ocelli,
like Caurinus and Apteropanorpa, less than four visual opsin messenger RNAs have
been identified. In addition, we found a Rh7-like opsin in transcriptome data
derived from larvae of the mecopteran Nannochorista, and in two flea species.
Peropsin expression was observed in two mecopterans. In light of these new data,
we question the hypothesis on monochromatic vision in the genus Panorpa. In a
broader phylogenetic perspective, it is suggested that the common ancestor of the
monophyletic taxon Antliophora (Diptera, Mecoptera and Siphonaptera) possessed
the full set of visual opsins, a Rh7-like opsin, and in addition a pteropsin as
well as a peropsin. In the course of evolution individual opsins were likely lost
in several lineages of this clade.
PMID- 29959338
TI - Motion-induced position shift in early Alzheimer's disease.
AB - The localization of object position in space is one of the most important visual
abilities in humans. Motion-induced position shift is a perceptual illusion in
which the position of a moving object is perceived to be shifted in the direction
of motion. In this study, we wanted to explore whether and how Alzheimer's
disease (AD) affects this illusion. We recruited a group of patients with early
AD and a group of age-matched healthy controls. In our experiments, two drifting
Gabor patches moving in opposite directions were presented and participants were
asked to report whether the upper Gabor appeared rightwards or leftwards of the
lower one. We measured the psychometric functions, of which the point of
subjective alignment was taken as the magnitude of motion-induced position shift.
We compared the position shift across the two groups at three different retinal
eccentricities. We found that position shifts were systematically smaller in the
AD group as comparing to the elderly control group. Our data demonstrated that AD
patients were less prone to motion-induced position shift. The results add to the
existing knowledge of perceptual deficits in AD patients. We suggest that motion
induced position shift may be effective as a new behavioral indicator for AD
identification.
PMID- 29959339
TI - mPEG-PLA and PLA-PEG-PLA nanoparticles as new carriers for delivery of
recombinant human Growth Hormone (rhGH).
AB - mPEG-PLA and PLA-PEG-PLA copolymeric nanoparticles with three different PLA to
PEG ratios are synthesized and used for encapsulation of recombinant human Growth
hormone (rhGH). The structure and composition of the synthesized copolymers were
analyzed by 1H NMR and GPC techniques. Moreover, morphology, encapsulation
efficiency (EE), cytotoxicity, release profile and stability of the encapsulated
rhGH were measured. Structural analysis of the prepared copolymers showed that
they were successfully synthesized with approximately expected molecular weight
and relatively low size distribution. It was also revealed that by increasing
amounts of PLA/PEG ratio, EE content and size of nanoparticles were increased.
Release profile evaluation of rhGH from both formulations indicated that
copolymeric nanoparticles of Di-B2 and Tri-B2 exhibited the best results among
the synthesized nanospheres, by having initial burst release of 17.5% and 28% and
then slow and constant release of rhGH up to 65% and 77% of the encapsulated
drug, respectively. Furthermore, results of HPLC, SDS-PAGE and CD analyses showed
stability of rhGH during encapsulation and release from nanoparticles. Finally,
the results showed that these two formulations provided safe and efficient
sustained release of rhGH for more than a month and they have the potential to do
further studies under in vivo conditions.
PMID- 29959340
TI - Optimization-based design of an elastostatic cloaking device.
AB - We present a new method for the design of devices to manipulate the displacement
field in Elastic materials. It consists of solving a nonlinear optimization
problem where the objective function defines the error in matching a desired
displacement field, and the design variables determine the required material
distribution within the device. In order to facilitate fabrication, the material
at a given point of the device is chosen from a set of predefined materials,
giving raise to a discrete optimization problem that is converted into a
continuous one using the Discrete Material Optimization technique. The candidate
materials maybe simple, isotropic materials, but the device made of them behaves
as a whole as a metamaterial, enabling the manipulation of the displacement field
in ways that are inconceivable in nature. As an example of application, a device
for elastostatic cloaking or unfeelability is designed.
PMID- 29959342
TI - Climate-induced shifts in leaf unfolding and frost risk of European trees and
shrubs.
AB - Climate warming has advanced leaf unfolding of trees and shrubs, thus extending
the growing period but potentially exposing plants to increased frost risk. The
relative shifts in the timing of leaf unfolding vs. the timing and intensity of
frost events determine whether frost risk changes under climate warming. Here we
test whether the frost risk for unfolding leaves of 13 European tree and shrub
species has changed over more than 60 years using dynamic state-space models and
phenological observations from 264 sites located between 200 and 1900 m a.s.l.
across Switzerland. Trees and shrubs currently feature sufficient safety margins
regarding frost risk, which increase from early- to late-leafing species and tend
to decrease with increasing elevation. Particularly after 1970 to 1990 and at
higher elevations, leaf unfolding has advanced across all species. While the time
between the last critical frost and leaf unfolding has shifted from predominantly
positive trends in the late 1950s and 1960s to a trend reversal since the 2000s,
the minimum temperature during leaf unfolding has mostly increased since the
1980s. These dynamic shifts in leaf unfolding and frost risk demonstrate species-
and site-specific responses of trees and shrubs to climate cooling and warming.
PMID- 29959341
TI - Semi-metals as potential thermoelectric materials.
AB - The best thermoelectric materials are believed to be heavily doped
semiconductors. The presence of a band gap is assumed to be essential to achieve
large thermoelectric power factor and figure of merit. In this work, we propose
semi-metals with large asymmetry between conduction and valence bands as an
alternative class of thermoelectric materials. To illustrate the idea, we study
semi-metallic HgTe in details experimentally and theoretically. We employ ab
initio calculations with hybrid exchange-correlation functional to accurately
describe the electronic band structure in conjunction with the Boltzmann
Transport theory to investigate the electronic transport properties. We calculate
the lattice thermal conductivity using first principles calculations and evaluate
the overall figure of merit. To validate our theoretical approach, we prepare
semi-metallic HgTe samples and characterize their transport properties. Our first
principles calculations agree well with the experimental data. We show that
intrinsic HgTe, a semimetal with large disparity in its electron and hole masses,
has a high thermoelectric power factor that is comparable to the best known
thermoelectric materials. Finally, we propose other possible materials with
similar band structures as potential candidates for thermoelectric applications.
PMID- 29959343
TI - A qualitative analysis of the bud ontogeny of Dracaena marginata using high
resolution magnetic resonance imaging.
AB - The development of the branch-stem-attachment of Dracaena marginata was analyzed
to clarify how a load-adapted arrangement of mechanically relevant tissues, i.e.
the vascular bundles with fiber caps, is established during ontogeny. For this
purpose, 3D images of four intact and developing buds of D. marginata were
repetitively acquired in vivo within the time span of 180 days using high
resolution magnetic resonance imaging, as this method allows for non-invasive and
non-destructive image acquisition. This methodical approach enabled the
classification of distinct ontogenetic stages revealing the complex ontogeny of
the branch-stem-attachment in D. marginata and the establishment of a load
adapted tissue arrangement within the junction between branch and main stem. This
further allows for a first biomimetic abstraction and the transfer into a
technical implementation of the form-structure-function principles found in
branchings in D. marginata.
PMID- 29959344
TI - A Donor Quality Index for liver transplantation: development, internal and
external validation.
AB - Organ shortage leads to using non-optimal liver grafts. Thus, to determine the
graft quality, the Donor Risk Index and the Eurotransplant Donor Risk Index have
been proposed. In a previous study we showed that neither could be validated on
the French database. Our aim was then dedicated to propose an adaptive Donor
Quality Index (DQI) using data from 3961 liver transplantation (LT) performed in
France between 2009 and 2013, with an external validation based on 1048 French LT
performed in 2014. Using Cox models and three different methods of selection, we
developed a new score and defined groups at risk. Model performance was assessed
by means of three measures of discrimination corrected by the optimism using a
bootstrap procedure. An external validation was also performed in order to
evaluate its calibration and discrimination. Five donor covariates were retained:
age, cause of death, intensive care unit stay, lowest MDRD creatinine clearance,
and liver type. Three groups at risk could be discriminated. The performances of
the model were satisfactory after internal validation. Calibration and
discrimination were preserved in the external validation dataset. The DQI
exhibited good properties and is potentially adaptive as an aid for better
guiding decision making for LT.
PMID- 29959345
TI - HrpE, the major component of the Xanthomonas type three protein secretion pilus,
elicits plant immunity responses.
AB - Like several pathogenic bacteria, Xanthomonas infect host plants through the
secretion of effector proteins by the Hrp pilus of the Type Three Protein
Secretion System (T3SS). HrpE protein was identified as the major structural
component of this pilus. Here, using the Xanthomonas citri subsp. citri (Xcc)
HrpE as a model, a novel role for this protein as an elicitor of plant defense
responses was found. HrpE triggers defense responses in host and non-host plants
revealed by the development of plant lesions, callose deposition, hydrogen
peroxide production and increase in the expression levels of genes related to
plant defense responses. Moreover, pre-infiltration of citrus or tomato leaves
with HrpE impairs later Xanthomonas infections. Particularly, HrpE C-terminal
region, conserved among Xanthomonas species, was sufficient to elicit these
responses. HrpE was able to interact with plant Glycine-Rich Proteins from citrus
(CsGRP) and Arabidopsis (AtGRP-3). Moreover, an Arabidopsis atgrp-3 knockout
mutant lost the capacity to respond to HrpE. This work demonstrate that plants
can recognize the conserved C-terminal region of the T3SS pilus HrpE protein as a
danger signal to defend themselves against Xanthomonas, triggering defense
responses that may be mediated by GRPs.
PMID- 29959346
TI - The pial vasculature of the mouse develops according to a sensory-independent
program.
AB - The cerebral vasculature is organized to supply the brain's metabolic needs.
Sensory deprivation during the early postnatal period causes altered neural
activity and lower metabolic demand. Neural activity is instructional for some
aspects of vascular development, and deprivation causes changes in capillary
density in the deprived brain region. However, it is not known if the pial
arteriole network, which contains many leptomeningeal anastomoses (LMAs) that
endow the network with redundancy against occlusions, is also affected by sensory
deprivation. We quantified the effects of early-life sensory deprivation via
whisker plucking on the densities of LMAs and penetrating arterioles (PAs) in
anatomically-identified primary sensory regions (vibrissae cortex,
forelimb/hindlimb cortex, visual cortex and auditory cortex) in mice. We found
that the densities of penetrating arterioles were the same across cortical
regions, though the hindlimb representation had a higher density of LMAs than
other sensory regions. We found that the densities of PAs and LMAs, as well as
quantitative measures of network topology, were not affected by sensory
deprivation. Our results show that the postnatal development of the pial arterial
network is robust to sensory deprivation.
PMID- 29959347
TI - The relationship of early recurrence of atrial fibrillation and the 3-month
integrity of the ablation lesion set.
AB - Early recurrence of atrial fibrillation (ERAF) after catheter-ablation (CA) can
be a transient phenomenon due to inflammation, or a harbinger of late AF
recurrence due to CA lesion (re)conduction. We studied the relationship between
ERAF and the 3-month CA lesions integrity. Forty one consecutive AF patients who
underwent a pulmonary vein isolation (PVI), roof line (RL) and mitral isthmus
line (MIL) CA were enrolled. At 3 months all patients underwent invasive
assessment of the lesion set integrity irrespective of ERAF. The PVI, RL and MIL
ablation was successful in 100.0%, 95.1% and 82.9% patients, respectively. At the
3-month remapping, a gap in PVI-lesion(s), RL or MIL was identified in 61.0%,
31.7% and 36.6% patients, respectively. Patients with (n = 17, 41.5%) compared to
those without ERAF (n = 24) had a significantly higher rate of any PV
reconnection (88.2% vs. 41.7%), the right PV(s)-reconnection (82.5% vs. 29.2%)
and the RL gap (52.9% vs. 16.7%), as well as a higher number of reconnected right
PVI-segments, all p < 0.05. On multivariate analysis, only the number of
reconnected right PVI-segments was associated with ERAF (OR 4.26, p = 0.004). The
ERAF following PVI + RL + MIL ablation was significantly related to 3-month PV
reconnections and the presence of RL gaps.
PMID- 29959348
TI - Increased nuclear DNA damage precedes mitochondrial dysfunction in peripheral
blood mononuclear cells from Huntington's disease patients.
AB - Huntington's disease (HD) is a progressive neurodegenerative disorder primarily
affecting the basal ganglia and is caused by expanded CAG repeats in the
huntingtin gene. Except for CAG sizing, mitochondrial and nuclear DNA (mtDNA and
nDNA) parameters have not yet proven to be representative biomarkers for disease
and future therapy. Here, we identified a general suppression of genes associated
with aerobic metabolism in peripheral blood mononuclear cells (PBMCs) from HD
patients compared to controls. In HD, the complex II subunit SDHB was lowered
although not sufficiently to affect complex II activity. Nevertheless, we found
decreased level of factors associated with mitochondrial biogenesis and an
associated dampening of the mitochondrial DNA damage frequency in HD, implying an
early defect in mitochondrial activity. In contrast to mtDNA, nDNA from HD
patients was four-fold more modified than controls and demonstrated that nDNA
integrity is severely reduced in HD. Interestingly, the level of nDNA damage
correlated inversely with the total functional capacity (TFC) score; an
established functional score of HD. Our data show that PBMCs are a promising
source to monitor HD progression and highlights nDNA damage and diverging
mitochondrial and nuclear genome responses representing early cellular
impairments in HD.
PMID- 29959349
TI - Nanopore sequencing as a revolutionary diagnostic tool for porcine viral enteric
disease complexes identifies porcine kobuvirus as an important enteric virus.
AB - Enteric diseases in swine are often caused by different pathogens and thus
metagenomics are a useful tool for diagnostics. The capacities of nanopore
sequencing for viral diagnostics were investigated here. First, cell culture
grown porcine epidemic diarrhea virus and rotavirus A were pooled and sequenced
on a MinION. Reads were already detected at 7 seconds after start of sequencing,
resulting in high sequencing depths (19.2 to 103.5X) after 3 h. Next, diarrheic
feces of a one-week-old piglet was analyzed. Almost all reads (99%) belonged to
bacteriophages, which may have reshaped the piglet's microbiome. Contigs matched
Bacteroides, Escherichia and Enterococcus phages. Moreover, porcine kobuvirus was
discovered in the feces for the first time in Belgium. Suckling piglets shed
kobuvirus from one week of age, but an association between peak of viral shedding
(106.42-107.01 copies/swab) and diarrheic signs was not observed during a follow
up study. Retrospective analysis showed the widespread (n = 25, 56.8% positive)
of genetically moderately related kobuviruses among Belgian diarrheic piglets.
MinION enables rapid detection of enteric viruses. Such new methodologies will
change diagnostics, but more extensive validations should be conducted. The true
enteric pathogenicity of porcine kobuvirus should be questioned, while its
subclinical importance cannot be excluded.
PMID- 29959350
TI - Utilization of lactic acid in human myotubes and interplay with glucose and fatty
acid metabolism.
AB - Once assumed only to be a waste product of anaerobe glycolytic activity, lactate
is now recognized as an energy source in skeletal muscles. While lactate
metabolism has been extensively studied in vivo, underlying cellular processes
are poorly described. This study aimed to examine lactate metabolism in cultured
human myotubes and to investigate effects of lactate exposure on metabolism of
oleic acid and glucose. Lactic acid, fatty acid and glucose metabolism were
studied in myotubes using [14C(U)]lactic acid, [14C]oleic acid and
[14C(U)]glucose, respectively. Myotubes expressed both the MCT1, MCT2, MCT3 and
MCT4 lactate transporters, and lactic acid was found to be a substrate for both
glycogen synthesis and lipid storage. Pyruvate and palmitic acid inhibited lactic
acid oxidation, whilst glucose and alpha-cyano-4-hydroxycinnamic acid inhibited
lactic acid uptake. Acute addition of lactic acid inhibited glucose and oleic
acid oxidation, whereas oleic acid uptake was increased. Pretreatment with lactic
acid for 24 h did not affect glucose or oleic acid metabolism. By replacing
glucose with lactic acid during the whole culturing period, glucose uptake and
oxidation were increased by 2.8-fold and 3-fold, respectively, and oleic acid
oxidation was increased 1.4-fold. Thus, lactic acid has an important role in
energy metabolism of human myotubes.
PMID- 29959352
TI - Potential Application of Saccharomyces cerevisiae and Rhizobium Immobilized in
Multi Walled Carbon Nanotubes to Adsorb Hexavalent Chromium.
AB - The presence of harmful contaminants in the waste stream is an important concern
worldwide. The convergence of biotechnology and nanoscience offers a sustainable
alternative in treating contaminated waters. Hexavalent chromium, being
carcinogenic deserves effective and sustainable methods for sequestration. Here
in, we report the immobilization of a prokaryote (Rhizobium) and eukaryote
(Saccharomyces cerevisiae) in multiwalled carbon nanotubes (MWCNTs) for the
effective adsorption of hexavalent chromium. The carboxylic groups were
introduced into the MWCNTs during oxidation using potassium permanganate and were
subjected to EDC-HOBT coupling to bind with microbial cell surface. FTIR, TGA,
BET, FESEM-EDAX, HRTEM, XPS and confocal microscopy were the investigative
techniques used to characterize the developed biosorbents. Experimental variables
such as pH, adsorbent dosage, kinetics, isotherms and thermodynamics were
investigated and it was observed that the system follows pseudo second order
kinetics with a best fit for Langmuir isotherm. Electrostatic interactions
between the functional groups in the microbial cell wall and hydrochromate anion
at pH 2.0 propel the adsorption mechanism. The lab scale column studies were
performed with higher volumes of the Cr(VI) contaminated water. Sodium hydroxide
was used as the desorbing agent for reuse of the biosorbents. The sustainable
biosorbents show prospects to treat chromium contaminated water.
PMID- 29959351
TI - Differential preservation of endogenous human and microbial DNA in dental
calculus and dentin.
AB - Dental calculus (calcified dental plaque) is prevalent in archaeological skeletal
collections and is a rich source of oral microbiome and host-derived ancient
biomolecules. Recently, it has been proposed that dental calculus may provide a
more robust environment for DNA preservation than other skeletal remains, but
this has not been systematically tested. In this study, shotgun-sequenced data
from paired dental calculus and dentin samples from 48 globally distributed
individuals are compared using a metagenomic approach. Overall, we find DNA from
dental calculus is consistently more abundant and less contaminated than DNA from
dentin. The majority of DNA in dental calculus is microbial and originates from
the oral microbiome; however, a small but consistent proportion of DNA (mean 0.08
+/- 0.08%, range 0.007-0.47%) derives from the host genome. Host DNA content
within dentin is variable (mean 13.70 +/- 18.62%, range 0.003-70.14%), and for a
subset of dentin samples (15.21%), oral bacteria contribute > 20% of total DNA.
Human DNA in dental calculus is highly fragmented, and is consistently shorter
than both microbial DNA in dental calculus and human DNA in paired dentin
samples. Finally, we find that microbial DNA fragmentation patterns are
associated with guanine-cytosine (GC) content, but not aspects of cellular
structure.
PMID- 29959353
TI - Electrical Stimulation with a Conductive Polymer Promotes Neurite Outgrowth and
Synaptogenesis in Primary Cortical Neurons in 3D.
AB - Deficits in neurite outgrowth and synaptogenesis have been recognized as an
underlying developmental aetiology of psychosis. Electrical stimulation promotes
neuronal induction including neurite outgrowth and branching. However, the effect
of electrical stimulation using 3D electrodes on neurite outgrowth and
synaptogenesis has not been explored. This study examined the effect of 3D
electrical stimulation on 3D primary cortical neuronal cultures. 3D electrical
stimulation improved neurite outgrowth in 3D neuronal cultures from both wild
type and NRG1-knockout (NRG1-KO) mice. The expression of synaptophysin and PSD95
were elevated under 3D electrical stimulation. Interestingly, 3D electrical
stimulation also improved neural cell aggregation as well as the expression of
PSA-NCAM. Our findings suggest that the 3D electrical stimulation system can
rescue neurite outgrowth deficits in a 3D culturing environment, one that more
closely resembles the in vivo biological system compared to more traditionally
used 2D cell culture, including the observation of cell aggregates as well as the
upregulated PSA-NCAM protein and transcript expression. This study provides a new
concept for a possible diagnostic platform for neurite deficits in
neurodevelopmental diseases, as well as a viable platform to test treatment
options (such as drug delivery) in combination with electrical stimulation.
PMID- 29959354
TI - Molecular mechanisms of tannin accumulation in Rhus galls and genes involved in
plant-insect interactions.
AB - For galling aphids and their hosts, tannins are crucial for plant-insect
interactions and for protecting the host plant from herbivory. Due to their
peculiar chemical characteristics, tannins from plant galls have been used for
medical and chemical purposes for more than 2000 years. In this study,
hydrolyzable tannin concentrations in galls increased from gall initiation
(38.34% on June 21) to maturation (74.79% on August 8), then decreased gradually
thereafter (58.83% on October 12). We identified a total of 81 genes (named as
GTS1-81) with putative roles in gallotannin biosynthesis and 22 genes (TS1-22) in
condensed tannin biosynthesis. We determined the expression profiles of these
genes by real-time PCR over the course of gall development. Multiple genes
encoding 1-beta-D-glucosyl transferases were identified, which may play a vital
role in gallotannin accumulation in plant galls. This study is the first attempt
to examine the molecular basis for the regulation of tannin accumulation in
insect gallnuts. The differentially expressed genes we identified may play
important roles in both tannin biosynthesis and plant-insect interactions.
PMID- 29959355
TI - Reciprocal cross-species induction of outer membrane vesicle biogenesis via
secreted factors.
AB - Delivery of cargo to target cells is fundamental to bacterial competitiveness.
One important but poorly understood system, ubiquitous among Gram-negative
organisms, involves packaging cargo into outer membrane vesicles (OMVs). These
biological nanoparticles are involved in processes ranging from toxin delivery to
cell-cell communication. Despite this, we know comparatively little about how
OMVs are formed. Building upon the discovery that the Pseudomonas Quinolone
Signal (PQS) stimulates OMV biogenesis in Pseudomonas aeruginosa, we proposed a
model where PQS interacts with the outer membrane to induce curvature and
ultimately OMV formation. Though this model is well supported in P. aeruginosa,
it remained unclear whether other organisms produce similar compounds. Here we
describe the development of a tightly controlled experimental system to test the
interaction of bacterially-produced factors with target cells. Using this system,
we show that multiple species respond to PQS by increasing OMV formation, that
PQS accumulates in the induced vesicles, and that other bacteria secrete OMV
promoting factors. Analysis of induced vesicles indicates that recipient-mediated
mechanisms exist to control vesicle size and that relatedness to the producer
organism can dictate susceptibility to OMV-inducing compounds. This work provides
evidence that small molecule induced OMV biogenesis is a widely conserved process
and that cross-talk between systems may influence OMV production in neighboring
bacteria.
PMID- 29959356
TI - Human and Microbial Proteins From Corpora Amylacea of Alzheimer's Disease.
AB - Corpora amylacea (CA) are spherical bodies mainly composed of polyglucans and, to
a lesser extent, proteins. They are abundant in brains from patients with
neurodegenerative diseases, particularly Alzheimer's disease. Although CA were
discovered many years ago, their precise origin and function remain obscure. CA
from the insular cortex of two Alzheimer's patients were purified and the protein
composition was assessed by proteomic analysis. A number of microbial proteins
were identified and fungal DNA was detected by nested PCR.A wide variety of human
proteins form part of CA. In addition, we unequivocally demonstrated several
fungal and bacterial proteins in purified CA. In addition to a variety of human
proteins, CA also contain fungal and bacterial polypeptides.In conclusion, this
paper suggests that the function of CA is to scavenge cellular debris provoked by
microbial infections.
PMID- 29959357
TI - Marine microalgae bioengineered Schizochytrium sp. meal hydrolysates inhibits
acute inflammation.
AB - Bioengineered marine microalgae Schizochytrium sp. is currently used to produce
docosahexaenoic acid (DHA). However, following DHA extraction, the remaining
protein-rich materials are not well utilized. In this study, we report that
marine microalgae bioengineered Schizochytrium sp. hydrolysate (MESH), which
exhibits a unique peptide profile as identified by Ultra Performance Liquid
Chromatography coupled with Q-TOF mass spectrometry(UPLC/Q-TOF-MS), ameliorated
bowel inflammation in mice. In a mouse model of experimentalcolitis induced by
dextran sulfate sodium, compared with the control mice, the mice treated with
MESH were highly resistant to colitis, as demonstrated by marked reductions in
body weight loss, clinical colitis scores, colonic histological damage, and
colonic inflammation. Mechanistically, MESH attenuated the induction of pro
inflammatory cytokines and increased the induction of anti-inflammatory
cytokines. MESH also promoted the proliferation of colonic crypt stem cells and
progenitor cells required for crypt repair. Collectively, these results reveal a
previously unrecognized role of MESH as a potential anti-inflammatory treatment
for colitis.
PMID- 29959358
TI - Variability in venom composition of European viper subspecies limits the cross
effectiveness of antivenoms.
AB - Medically relevant cases of snakebite in Europe are predominately caused by
European vipers of the genus Vipera. Systemic envenoming by European vipers can
cause severe pathology in humans and different clinical manifestations are
associated with different members of this genus. The most representative vipers
in Europe are V. aspis and V. berus and neurological symptoms have been reported
in humans envenomed by the former but not by the latter species. In this study we
determined the toxicological profile of V. aspis and V. berus venoms in vivo in
mice and we tested the effectiveness of two antivenoms, commonly used as
antidotes, in counteracting the specific activities of the two venoms. We found
that V. aspis, but not V. berus, is neurotoxic and that this effect is due to the
degeneration of peripheral nerve terminals at the NMJ and is not neutralized by
the two tested antisera. Differently, V. berus causes a haemorrhagic effect,
which is efficiently contrasted by the same antivenoms. These results indicate
that the effectiveness of different antisera is strongly influenced by the
variable composition of the venoms and reinforce the arguments supporting the use
polyvalent antivenoms.
PMID- 29959359
TI - Circulating miR-30a-5p as a prognostic biomarker of left ventricular dysfunction
after acute myocardial infarction.
AB - Left ventricular (LV) dysfunction after acute myocardial infarction (AMI) is
associated with an increased risk of heart failure (HF) development. Diverse
microRNAs (miRNAs) have been shown to appear in the bloodstream following various
cardiovascular events. The aim of this study was to identify prognostic miRNAs
associated with LV dysfunction following AMI. Patients were divided into
subgroups comprising patients who developed or not LV dysfunction within six
months of the infarction. miRNA profiles were determined in plasma and serum
samples of the patients on the first day of AMI. Levels of 14 plasma miRNAs and
16 serum miRNAs were significantly different in samples from AMI patients who
later developed LV dysfunction compared to those who did not. Two miRNAs were up
regulated in both types of material. Validation in an independent group of
patients, using droplet digital PCR (ddPCR) confirmed that miR-30a-5p was
significantly elevated on admission in those patients who developed LV
dysfunction and HF symptoms six months after AMI. A bioinformatics analysis
indicated that miR-30a-5p may regulate genes involved in cardiovascular
pathogenesis. This study demonstrates, for the first time, a prognostic value of
circulating miR-30a-5p and its association with LV dysfunction and symptoms of HF
after AMI.
PMID- 29959360
TI - Conformation-dependent binding of a Tetrastatin peptide to alphavbeta3 integrin
decreases melanoma progression through FAK/PI3K/Akt pathway inhibition.
AB - Tetrastatin, a 230 amino acid sequence from collagen IV, was previously
demonstrated to inhibit melanoma progression. In the present paper, we identified
the minimal active sequence (QKISRCQVCVKYS: QS-13) that reproduced the anti-tumor
effects of whole Tetrastatin in vivo and in vitro on melanoma cell proliferation,
migration and invasion. We demonstrated that QS-13 binds to SK-MEL-28 melanoma
cells through the alphavbeta3 integrin using blocking antibody and beta3 integrin
subunit siRNAs strategies. Relevant QS-13 conformations were extracted from
molecular dynamics simulations and their interactions with alphaVbeta3 integrin
were analyzed by docking experiments to determine the binding areas and the QS-13
amino acids crucial for the binding. The in silico results were confirmed by in
vitro experiments. Indeed, QS-13 binding to SK-MEL-28 was dependent on the
presence of a disulfide-bound as shown by mass spectroscopy and the binding site
on alphaVbeta3 was located in close vicinity to the RGD binding site. QS-13
binding inhibits the FAK/PI3K/Akt pathway, a transduction pathway that is largely
involved in tumor cell proliferation and migration. Taken together, our results
demonstrate that the QS-13 peptide binds alphavbeta3 integrin in a conformation
dependent manner and is a potent antitumor agent that could target cancer cells
through alphaVbeta3.
PMID- 29959361
TI - Neonatal- maternal separation primes zymogenic cells in the rat gastric mucosa
through glucocorticoid receptor activity.
AB - Neonatal- Maternal Separation (NMS) deprives mammals from breastfeeding and
maternal care, influencing growth during suckling- weaning transition. In the
gastric mucosa, Mist1 (encoded by Bhlha15 gene) and moesin organize the secretory
apparatus for pepsinogen C in zymogenic cells. Our current hypothesis was that
NMS would change corticosterone activity through receptors (GR), which would
modify molecules involved in zymogenic cell differentiation in rats. We found
that NMS increased corticosterone levels from 18 days onwards, as GR decreased in
the gastric mucosa. However, as nuclear GR was detected, we investigated receptor
binding to responsive elements (GRE) and observed an augment in NMS groups. Next,
we demonstrated that NMS increased zymogenic population (18 and and 30 days), and
targeted Mist1 and moesin. Finally, we searched for evolutionarily conserved
sequences that contained GRE in genes involved in pepsinogen C secretion, and
found that the genomic regions of Bhlha15 and PgC contained sites highly likely
to be responsive to glucocorticoids. We suggest that NMS triggers GR- GRE to
enhance the expression and to prime genes that organize cellular architecture in
zymogenic population for PgC function. As pepsinogen C- pepsin is essential for
digestion, disturbance of parenting through NMS might alter functions of gastric
mucosa in a permanent manner.
PMID- 29959362
TI - Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression in Pancreatic
Cancer.
AB - Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2
(LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial
to-mesenchymal transition (EMT) in various cancers. This study aimed to explore
the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the
context of EMT status. LOX family mRNA expression was measured in PC cell lines,
and LOXL2 protein levels were examined in surgical specimens resected from 170
patients with PC. Higher LOXL2 expression was observed in cell lines from
mesenchymal type PC than in those from epithelial type PC. A significant
correlation between LOXL2 expression and the EMT status defined based on the
expression of E-cadherin and vimentin was observed in surgical specimens (P <
0.01). The disease-free survival and overall survival rates among patients with
low LOXL2 expression were significantly better than those among patients with
high LOXL2 expression (P < 0.001). According to the multivariate analysis, high
LOXL2 expression (P = 0.03) was a significant independent prognostic factor for
patients with PC. Additionally, LOX inhibition significantly decreased PC cell
proliferation, migration, and invasion in vitro. In conclusion, LOXL2 expression
is potentially associated with PC progression, and LOXL2 expression represents a
biomarker for predicting the prognosis of patients with PC who have undergone
complete resection.
PMID- 29959364
TI - Gait Estimation from Anatomical Foot Parameters Measured by a Foot Feature
Measurement System using a Deep Neural Network Model.
AB - An accurate and credible measurement of human gait is essential in multiple areas
of medical science and rehabilitation. Yet, the methods currently available are
not only arduous but also costly. Researchers who investigated the relationship
between foot and gait parameters have found that the two parameters are closely
interrelated and suggested that measuring foot characteristics can be an
alternative to the strenuous quantification currently in use. This study aims to
verify the potential of foot characteristics in predicting the actual gait
temporo-spatial parameters and to develop a deep neural network (DNN) model that
can estimate and quantify the gait temporo-spatial parameters from foot
characteristics. The foot features in sitting, standing, and one-leg standing
conditions of 42 subjects were used as the input data and gait temporo-spatial
parameters at fast, normal, and slow speed were set as the output of the DNN
regressor. With the prediction accuracy of 95% or higher, the feasibility of the
developed model was verified. This study might be the first in attempting
experimental verification of the foot features serving as predictors of
individual gait. The DNN regressor will help researchers improve the data pool
with less labor and expense when some limitations get properly overcome.
PMID- 29959363
TI - Role of the hippocampal CA1 region in incremental value learning.
AB - It is generally believed that the hippocampus plays a crucial role in declarative
memory-remembering facts and events-but not in gradual stimulus-response
association or incremental value learning. Based on the finding that CA1 conveys
strong value signals during dynamic foraging, we investigated the possibility
that the hippocampus contributes to incremental value learning. Specifically, we
examined effects of inactivating different subregions of the dorsal hippocampus
on behavioral performance of mice performing a dynamic foraging task in a
modified T-maze. A reinforcement learning model-based analysis indicated that
inactivation of CA1, but not dentate gyrus, CA3, or CA2, impaired trial-by-trial
updating of chosen value without affecting value-dependent action selection. As a
result, it took longer for CA1-inactivated mice to bias their choices toward the
higher-reward-probability target after changes in reward probability. Our results
indicate, contrary to the traditional view, that the hippocampus, especially CA1,
might contribute to incremental value learning under certain circumstances.
PMID- 29959365
TI - Visual cues do not enhance sea lion pups' response to multimodal maternal cues.
AB - Mammals use multiple sensory cues for mother-offspring recognition. While the
role of single sensory cues has been well studied, we lack information about how
multiple cues produced by mothers are integrated by their offspring. Knowing that
Australian sea lion (Neophoca cinerea) pups recognise their mother's calls, we
first tested whether visual cues are used by pups to discriminate between
conspecifics of different age classes (adult female vs pup). We then examined if
adding a visual stimulus to an acoustic cue enhances vocal responsiveness of
Australian sea lion pups, by presenting wild individuals with either a visual cue
(female 3D-model), an acoustic cue (mother's call), or both simultaneously, and
observing their reaction. We showed that visual cues can be used by pups to
distinguish adult females from other individuals, however we found no enhancement
effect of these cues on the response in a multimodal scenario. Audio-only cues
prompted a similar reaction to audio-visual cues that was significantly stronger
than pup response to visual-only cues. Our results suggest that visual cues are
dominated by acoustic cues and that pups rely on the latter in mother
recognition.
PMID- 29959366
TI - Seasonal Response of North Western Pacific Marine Ecosystems to Deposition of
Atmospheric Inorganic Nitrogen Compounds from East Asia.
AB - The contribution of the atmospheric deposition of inorganic nitrogen compounds
produced in East Asia to the marine ecosystems of the North Western Pacific Ocean
(NWPO) was investigated in this study using a 3-D lower trophic-marine ecosystem
model (NEMURO) combined with an atmospheric regional chemical transport model
(WRF-CMAQ). The monthly mean values for the wet and dry deposition of nitrogen
compounds, including gases (HNO3 and NH3) and aerosol particles (NO3- and NH4+),
were determined using the WRF-CMAQ for the NWPO from 2009-2016. These values were
input into the NEMURO as an additional nitrogen source. The NEMURO indicated that
the annual average chlorophyll mass concentration at the surface in the
subtropical region (20 degrees N-30 degrees N; 125 degrees E-150 degrees E) of
the NWPO increased from 0.04 to 0.10 mg/m3. Similarly, the gross primary
productivity, integrated over sea depths of 0-200 m, increased from 85 to 147 mg
C/m2/day because of this deposition. This study indicates that the supply of
atmospheric inorganic nitrogen compounds from East Asia to the NWPO could have a
high nutrient impact on the marine ecosystem in the subtropical region.
PMID- 29959367
TI - Ultra-broadband and compact graphene-on-silicon integrated waveguide mode
filters.
AB - Increasing bandwidth demands in optical communications necessitates the
introduction of mode-division multiplexing (MDM) on top of the existing
wavelength-division multiplexing (WDM) systems. Simultaneous management of both
multiplexing systems will be a complex task, and there is the possibility of
signal degradation through modal crosstalk. Here, we propose graphene-on-silicon
(GOS) integrated waveguide mode filters to suppress the propagation of spurious
waveguide modes at the telecommunications wavelength. Graphene's high fabrication
tolerance potentially enables surgical tailoring and deployment at targeted
segments on the waveguide to absorb the undesired TE0 or TE1 modes. The proposed
GOS waveguide mode filters can potentially improve the performance and reduce the
device footprint of MDM systems.
PMID- 29959368
TI - The Predictive Value of Head Circumference Growth during the First Year of Life
on Early Child Traits.
AB - Atypical head circumference (HC) growth has been associated with
neurodevelopmental disorders. However, whether it is associated with specific
aspects of development in early childhood in the general population is unknown.
The objective of this study was to assess the predictive value of HC growth as an
early biomarker of behavioral traits. We examined longitudinal associations
between HC growth from 0 to 12 months and temperament, cognitive, and motor
development at 24 months. A subsample of healthy children (N = 756) was drawn
from the 3D (Design, Develop, Discover) cohort study. Early HC growth was modeled
with latent growth curve analysis. Greater postnatal HC growth predicted lower
temperamental effortful control and lower surgency/extraversion in boys. HC
growth did not predict cognitive or fine motor scores, but did predict greater
gross motor skills in boys. No significant effect of HC growth was found in
girls. This study is the first to demonstrate an association between postnatal HC
growth and specific aspects of child development in a healthy population. Results
suggest HC growth overshadows brain mechanisms involved in behavioral traits in
early infancy. Whether links are maintained throughout development and the
mechanisms involved correspond to traits found in atypical populations remains to
be studied.
PMID- 29959369
TI - Whole genome sequencing reveals widespread distribution of typhoidal toxin genes
and VirB/D4 plasmids in bovine-associated nontyphoidal Salmonella.
AB - Nontyphoidal Salmonella (NTS) is a common pathogen in food-producing animals and
a public health concern worldwide. Various NTS serovars may be present in
apparently healthy animals. This could result in carcass contamination during the
slaughter process leading to human exposure. While most genomic research has
focused on Salmonella pathogenesis, little is known on the factors associated
with subclinical infections and environmental persistence. We report here the
widespread distribution of typhoidal toxin genes (i. e. the cdtB islet, hlyE,
taiA), among NTS strains from a beef slaughter operation (n = 39) and from
epidemiologically unconnected ground beef (n = 20). These genes were present in
76% of the strains, regardless of serovar, isolation source or geographical
location. Moreover, strains that predominated in the slaughterhouse carry plasmid
borne type IV secretion systems (T4SS), which have been linked to persistent
infections in numerous pathogens. Population genomics supports clonal
dissemination of NTS along the food production chain, highlighting its role as
reservoir of genetic variability in the environment. Overall, the study provides
a thorough characterization of serovar diversity and genomic features of beef
associated NTS in Mexico. Furthermore, it reveals how common genetic factors
could partially explain the emergence and persistence of certain NTS serovars in
the beef industry.
PMID- 29959370
TI - A novel sample holder for 4D live cell imaging to study cellular dynamics in
complex 3D tissue cultures.
AB - Three dimensional (3D) co-cultures to mimic cellular dynamics have brought
significant impacts in tissue engineering approaches for biomedical research.
Herein, we present a novel sample holder combined with time-lapse fluorescence
imaging technique, referred as 4D live cell imaging, allowing direct
visualization of various cells up to 24 hours. We further extended our approach
to monitor kinetics and dynamics of particle uptake by cells and translocation
across tissue membranes.
PMID- 29959371
TI - Jia-Jian-Di-Huang-Yin-Zi decoction exerts neuroprotective effects on dopaminergic
neurons and their microenvironment.
AB - As a classical prescription of Traditional Chinese medicine, the Jia-Jian-Di
Huang-Yin-Zi (JJDHYZ) decoction has long been used to treat movement disorders.
The present study evaluated the effects of JJDHYZ on dopaminergic (DA) neurons
and their survival-enhancing microenvironment as well as the possible mechanisms
involved using a mouse model of Parkinson's disease. In MPTP-lesioned mice, a
high dosage of JJDHYZ (34 g/kg/day) attenuated the loss of DA neurons, reversed
the dopamine depletion, and improved the expression of glial-derived neurotrophic
factor (GDNF) compared to the untreated model group. JJDHYZ also protected the
ultrastructure of the blood-brain barrier (BBB) and tight junction proteins by
inhibiting the activation of microglia and astrocytes besides the increase in
three types of matrix metalloproteinases in the substantia nigra. In conclusion,
the JJDHYZ-high dosage (JJDHYZ-H) group exhibited the neuroprotection of DA
neurons, and the underlying mechanism may be related to the survival-enhancing
microenvironment of the DA neurons.
PMID- 29959372
TI - Protein Secondary Structure Prediction Based on Data Partition and Semi-Random
Subspace Method.
AB - Protein secondary structure prediction is one of the most important and
challenging problems in bioinformatics. Machine learning techniques have been
applied to solve the problem and have gained substantial success in this research
area. However there is still room for improvement toward the theoretical limit.
In this paper, we present a novel method for protein secondary structure
prediction based on a data partition and semi-random subspace method (PSRSM).
Data partitioning is an important strategy for our method. First, the protein
training dataset was partitioned into several subsets based on the length of the
protein sequence. Then we trained base classifiers on the subspace data generated
by the semi-random subspace method, and combined base classifiers by majority
vote rule into ensemble classifiers on each subset. Multiple classifiers were
trained on different subsets. These different classifiers were used to predict
the secondary structures of different proteins according to the protein sequence
length. Experiments are performed on 25PDB, CB513, CASP10, CASP11, CASP12, and
T100 datasets, and the good performance of 86.38%, 84.53%, 85.51%, 85.89%,
85.55%, and 85.09% is achieved respectively. Experimental results showed that our
method outperforms other state-of-the-art methods.
PMID- 29959373
TI - The role of B7-1 in proteinuria of glomerular origin.
AB - The damage and loss of podocytes is a primary hallmark of nephrotic syndrome. In
the pursuit of targetable molecules that are involved in podocyte
pathophysiology, some studies have identified B7-1 (also known as CD80) as a
potential biomarker. Furthermore, B7-1 blockade has been proposed as a podocyte
specific treatment for patients with nephrotic syndrome who have limited
therapeutic options, such as those with focal segmental glomerulosclerosis,
minimal change disease, diabetic nephropathy and lupus nephritis. In this
Perspectives article, we describe and compare supporting and contradicting data
on the role of podocyte B7-1 in the pathogenesis of various podocytopathies.
Moreover, we highlight crucial issues that should be addressed urgently - such as
standardization of sample processing time, material conservation and antibody
usage in immunohistochemical protocols - as a clinical trial that is
investigating the efficacy of B7-1 blockade in treatment-resistant nephrotic
syndrome is ongoing.
PMID- 29959374
TI - Prevalence of metabolic syndrome risk factors and their relationships with renal
function in Chinese centenarians.
AB - As the first time, this study was to investigate the prevalence of metabolic
syndrome (MetS) risk factors and explore their relationships with renal function
in Chinese centenarians. China Hainan Centenarian Cohort Study was performed in
18 cities and counties of Hainan Province. Home interview, physical examination
and blood analysis were performed in 874 centenarians following standard
procedures. Prevalence of MetS was 15.6% (136 centenarians). There were 229
centenarians with abdominal obesity (26.2%), 645 centenarians (73.8%) with
hypertension, 349 centenarians with dyslipidemia (39.9%) and 92 centenarians with
diabetes mellitus (10.5%). In multivariate linear regression, age, smoking, waist
circumstance (WC), systolic blood pressure (SBP) and triglyceride levels were
inversely and diastolic blood pressure (DBP) levels were positively associated
with glomerular filtration rate levels (P < 0.05 for all). This study reported
low prevalence of MetS risk factors and demonstrated that age, smoking, abdominal
obesity (WC), hypertension (SBP and DBP) and triglyceride levels were
independently associated with renal function in Chinese centenarians. This study
provided reliable data about Chinese centenarians, analyzed significant
relationships between Mets risk factors and renal function, and explained
possible reason (low prevalence of MetS and its risk factors) and mechanism
(interrelationship of age, Mets risk factors with renal function) of longevity.
PMID- 29959375
TI - 1-Methyl-D-tryptophan Reduces Tumor CD133+ cells, Wnt/beta-catenin and NF
kappabetap65 while Enhances Lymphocytes NF-kappabeta2, STAT3, and STAT4 Pathways
in Murine Pancreatic Adenocarcinoma.
AB - 1-Methyl-D-tryptophan (1-MT) is extensively utilized in preclinical trials to
deplete indoleamine 2,3-dioxigenase (IDO) activity and kynurenine pathway. Since
IDO related signaling pathways aren't well understood, some clinical reports
affirmed IDO inhibiting therapeutic significance. Therefore, we did use direct
tumor autologous antigens vaccination and 1-MT without chemotherapy to explore
biological mechanisms and immunomodulations of 1-MT that motivate antitumor
responses. However, DCs antigen-uptake capability, anti-tumor efficiency, intra
tumor and intracellular cytokines were assessed. Besides, CD133+ cells viability
and tumor biomarkers were investigated. Splenocytes responses and their signaling
pathways such TLRs 2 to 9, NF-kappabeta1-2, Wnt/beta-catenin and TGF-beta were
dissected. Results evinced that a regimen of 1-MT and TAAs significantly reduced
CSC CD133 + viability inside tumor microenvironment, besides increasing tumor
cells necrosis and apoptosis. Expression of TGF-beta, IDO, RANTES, and PDL-1 was
also significantly reduced. Interestingly, 1-MT enhanced lymphocytes TLR2, TLR7,
TLR8, and TLR9 pathways. It motivated lymphocytes' NF-kappabeta2, STAT3, and
STAT4 pathways, while reduced tumors' NF-kappabetap65 and Wnt/beta-catenin
signaling pathways. We found that periphery and intra-tumor Treg cells were
significantly decreased. In conclusion, depletion of indoleamine 2,3-dioxigenase
activity evidenced IDO relation with tumor stem cells proliferation pathways.
Furthermore, 1-MT supports immunotherapeutic vaccines susceptibility and tumor
specific targeting by reducing tumorgensis signaling pathways.
PMID- 29959376
TI - Multi-centennial fluctuations of radionuclide production rates are modulated by
the Earth's magnetic field.
AB - The production of cosmogenic isotopes offers a unique way to reconstruct solar
activity during the Holocene. It is influenced by both the solar and Earth
magnetic fields and thus their combined effect needs to be disentangled to infer
past solar irradiance. Nowadays, it is assumed that the long-term variations of
cosmogenic production are modulated by the geomagnetic field and that the solar
field dominates over shorter wavelengths. In this process, the effects of the non
dipolar terms of the geomagnetic field are considered negligible. Here we analyse
these assumptions and demonstrate that, for a constant solar modulation
potential, the geomagnetic field exerts a strong modulation of multi-centennial
to millennial wavelengths (periods of 800 and 2200 yr). Moreover, we demonstrate
that the non-dipole terms derived from the harmonic degree 3 and above produce
maximum differences of 7% in the global average radiocarbon production rate. The
results are supported by the identification, for the first time, of a robust
coherence between the production rates independently estimated from geomagnetic
reconstructions and that inferred from natural archives. This implies the need to
review past solar forcing reconstructions, with important implications both for
the assessment of solar-climate relationships as well as for the present and
future generation of paleoclimate models.
PMID- 29959377
TI - A broadband tunable terahertz negative refractive index metamaterial.
AB - A strategy to greatly broaden negative refractive index (NRI) band, reduce loss
and ease bi-anisotropy of NRI metamaterials (MMs) has been proposed at terahertz
frequencies. Due to the symmetric structure of the MM, the transmission and
refractive index are independent to polarizations of incident radiations, and a
broadband NRI is obtainable for the range of the incident angle from 0 degrees
to 26 degrees . In addition, THz MMs' properties such as transmission, phase and
negative refraction exhibit a real-time response by controlling the temperature.
The results indicate that the maximum bands of the negative and double-negative
refraction are 1.66 THz and 1.37 THz for the temperature of 40 degrees C and 63
degrees C, respectively. The figure of merit of the MMs exceeds 10 (that is, low
loss) as the frequency increases from 2.44 THz to 2.56 THz in the working
temperature range, and the maximum figure of merit is 83.77 at 2.01 THz where the
refractive index is -2.81 for a given temperature of 40 degrees C. Furthermore,
the negative refraction of the MMs at the low loss band is verified by the
classical method of the wedge, and the symmetric slab waveguide based on the
proposed MM has many unique properties.
PMID- 29959378
TI - Effect of ionic strength and seawater cations on hagfish slime formation.
AB - The defensive slime of hagfish consists of a polyanionic mucin hydrogel that
synergistically interacts with a fiber network forming a coherent and elastic
hydrogel in high ionic strength seawater. In seawater, the slime deploys in less
than a second entrapping large quantities of water by a well-timed thread skein
unravelling and mucous gel swelling. This rapid and vast hydrogel formation is
intriguing, as high ionic strength conditions generally counteract the swelling
speed and ratio of polyelectrolyte hydrogels. In this work we investigate the
effect of ionic strength and seawater cations on slime formation dynamics and
functionality. In the absence of ionic strength skeins swell radially and unravel
uncontrolled, probably causing tangling and creating a confined thread network
that entraps limited water. At high ionic strength skeins unravel, but create a
collapsed and dense fiber network. High ionic strength conditions therefore seem
crucial for controlled skein unraveling, however not sufficient for water
retention. Only the presence of naturally occurring Ca2+ or Mg2+-ions allowed for
an expanded network and full water retention probably due to Ca2+-mediated
vesicle rupture and cross-linking of the mucin. Our study demonstrates that
hagfish slime deployment is a well-timed, ionic-strength, and divalent-cation
dependent dynamic hydrogel formation process.
PMID- 29959379
TI - The adiponectin promoter activator NP-1 induces high levels of circulating
TNFalpha and weight loss in obese (fa/fa) Zucker rats.
AB - Chronic NP-1 administration reduces body weight and hepatic steatosis despite
induction of tolerance in adiponectin gene transcription with respect to the
acute actions of this drug. This study explored the hypothesis that NP-1 could
exert these effects through mechanisms independent of adiponectin. To this aim,
we took advantage of the Zucker (fa/fa) rat model, which exhibits obesity, fatty
liver and elevated leptin and adiponectin levels. Body weight and food intake
were reduced after chronic NP-1 treatment. Plasma TNFalpha concentrations were
elevated but no increase in adiponectin was found. Even so, NP-1 ameliorated
fatty liver and corrected dyslipidemia by mechanisms probably associated with
reduced feeding, transcription of Cpt1 and down-regulation of Hmgcr-CoA
expression. In brown fat tissue NP-1 increased Dnmt1 (inhibitor of Adipoq) while
it reduced Ucp1 expression and heat production, which excludes thermogenesis as a
mechanism of the NP-1 slimming effect. The anti-obesity action of chronic NP-1
administration might be mediated by TNFalpha, which is known to have anorectic
actions in the hypothalamus and to regulate both Dmnt1 and Ucp1 expression in
adipose tissues. This finding opens up the possibility of using NP-1-mediated
TNFalpha-induced weight loss as an innovative treatment of complicated obesity
under strict pharmacologic control.
PMID- 29959381
TI - Alteration of circulating natural autoantibodies to CD25-derived peptide antigens
and FOXP3 in non-small cell lung cancer.
AB - Natural autoantibody is a key component for immune surveillance function.
Regulatory T (Treg) cells play indispensable roles in promoting tumorigenesis via
immune escape mechanisms. Both CD25 and FOXP3 are specific markers for Treg cells
and their natural autoantibodies may be involved in anticancer activities. This
work was designed to develop an in-house enzyme-linked immunosorbent assay
(ELISA) to examine plasma natural IgG against CD25 and FOXP3 in non-small cell
lung cancer (NSCLC). Compared with control subjects, NSCLC patients had
significantly higher levels of plasma IgG for CD25a (Z = -8.05, P < 0.001) and
FOXP3 (Z = -4.17, P < 0.001), lower levels for CD25b (Z = -3.58, P < 0.001), and
a trend toward lower levels for CD25c (Z = -1.70, P = 0.09). Interestingly, the
anti-CD25b IgG assay had a sensitivity of 25.0% against a specificity of 95.0% in
an early stage patients (T1N0M0) who showed the lowest anti-CD25b IgG levels
among 4 subgroups classified based on staging information. Kaplan-Meier survival
analysis showed that patients with high anti-FOXP3 IgG levels had shorter
survival than those with low anti-FOXP3 IgG levels (chi2 = 3.75, P = 0.05). In
conclusion, anti-CD25b IgG may be a promising biomarker in terms of screening
individuals at high risk of lung cancer.
PMID- 29959380
TI - Morphological, genomic and transcriptomic responses of Klebsiella pneumoniae to
the last-line antibiotic colistin.
AB - Colistin remains one of the few antibiotics effective against multi-drug
resistant (MDR) hospital pathogens, such as Klebsiella pneumoniae. Yet resistance
to this last-line drug is rapidly increasing. Characterized mechanisms of colR in
K. pneumoniae are largely due to chromosomal mutations in two-component
regulators, although a plasmid-mediated colR mechanism has recently been
uncovered. However, the effects of intrinsic colistin resistance are yet to be
characterized on a whole-genome level. Here, we used a genomics-based approach to
understand the mechanisms of adaptive colR acquisition in K. pneumoniae. In
controlled directed-evolution experiments we observed two distinct paths to
colistin resistance acquisition. Whole genome sequencing identified mutations in
two colistin resistance genes: in the known colR regulator phoQ which became
fixed in the population and resulted in a single amino acid change, and unstable
minority variants in the recently described two-component sensor crrB. Through
RNAseq and microscopy, we reveal the broad range of effects that colistin
exposure has on the cell. This study is the first to use genomics to identify a
population of minority variants with mutations in a colR gene in K. pneumoniae.
PMID- 29959382
TI - Whole-exome sequencing in intellectual disability; cost before and after a
diagnosis.
AB - Clinical application of whole-exome and whole-genome sequencing (WES and WGS) has
led to an increasing interest in how it could drive healthcare decisions. As with
any healthcare innovation, implementation of next-generation sequencing in the
clinic raises questions on affordability and costing impact for society as a
whole. We retrospectively analyzed medical records of 370 patients with ID who
had undergone WES at various stages of their diagnostic trajectory. We collected
all medical interventions performed on these patients at the University Medical
Center Utrecht (UMCU), Utrecht, the Netherlands. We categorized the patients
according to their WES-based preliminary diagnosis ("yes", "no", and
"uncertain"), and assessed the per-patient healthcare activities and
corresponding costs before (pre) and after (post) genetic diagnosis. The WES
specific diagnostic yield among the 370 patients was 35% (128 patients). Pre-WES
costs were ?7.225 on average. Highest average costs were observed for laboratory
based tests, including genetics, followed by consults. Compared to pre-WES costs,
the post-WES costs were on average 80% lower per patient, irrespective of the WES
based diagnostic outcome. Application of WES results in a considerable reduction
of healthcare costs, not just in current settings, but even more so when applied
earlier in the diagnostic trajectory (genetics-first). In such context, WES may
replace less cost-effective traditional technologies without compromising the
diagnostic yield. Moreover, WES appears to harbor an intrinsic "end-of
trajectory" effect; regardless of the diagnosis, downstream medical interventions
decrease substantially in both number and costs.
PMID- 29959384
TI - Circa 1 Ga sub-seafloor hydrothermal alteration imprinted on the Horoman
peridotite massif.
AB - The chemical compositions of the residues of the mantle melting that produces mid
ocean ridge basalt can be altered by fluid-rock interactions at spreading ridges
and, possibly, during seawater penetration along bending-related faults in plates
approaching trenches. This chemically modified rock, if subducted deeply and
after long-term residence within the deep Earth, is a potential source of
chemical heterogeneity in the mantle. Here, we demonstrate that peridotites from
the Horoman massif preserve the chemical signatures of sub-seafloor hydrothermal
(SSH) alteration at a mid-ocean ridge approximately one billion years ago. These
rocks have evolved chemically subsequent to this SSH alteration; however, they
retain the SSH-associated enrichments in fluid mobile elements and H2O despite
their long-term residence within the mantle. Our results indicate that ancient
SSH alteration resulting in the production of sulfide leads to Pb enrichment that
could affect the present-day Pb isotopic evolution of the silicate earth.
Evidence from the Horoman massif of the recycling of hydrous refractory domains
into the mantle suggests that both the flux of H2O content into the mantle and
the size of the mantle H2O reservoir are higher than have been estimated
recently.
PMID- 29959383
TI - Multiplex STR amplification sensitivity in a silicon microchip.
AB - The demand for solutions to perform forensic DNA profiling outside of centralized
laboratories is increasing. We here demonstrate highly sensitive STR
amplification using a silicon micro-PCR (uPCR) chip. Exploiting industry-standard
semiconductor manufacturing processes, a device was fabricated that features a
small form factor thanks to an integrated heating element covering three parallel
micro-reactors with a reaction volume of 0.5 ul each. Diluted reference DNA
samples (1 ng-31 pg) were amplified on the uPCR chip using the forensically
validated AmpFISTR Identifier Plus kit, followed by conventional capillary
electrophoresis. Complete STR profiles were generated with input DNA quantities
down to 62 pg. Occasional allelic dropouts were observed from 31 pg downward. On
chip STR profiles were compared with those of identical samples amplified using a
conventional thermal cycler for direct comparison of amplification sensitivity in
a forensic setting. The observed sensitivity was in line with kit specifications
for both uPCR and conventional PCR. Finally, a rapid amplification protocol was
developed. Complete STR profiles could be generated in less than 17 minutes from
as little as 125 pg template DNA. Together, our results are an important step
towards the development of commercial, mass-produced, relatively cheap, handheld
devices for on-site testing in forensic DNA analysis.
PMID- 29959385
TI - Estimation of intraocular lens position from full crystalline lens geometry:
towards a new generation of intraocular lens power calculation formulas.
AB - In a cataract surgery, the opacified crystalline lens is replaced by an
artificial intraocular lens (IOL). To optimize the visual quality after surgery,
the intraocular lens to be implanted must be selected preoperatively for every
individual patient. Different generations of formulas have been proposed for
selecting the intraocular lens dioptric power as a function of its estimated
postoperative position. However, very few formulas include crystalline lens
information, in most cases only one-dimensional. The present study proposes a new
formula to preoperatively estimate the postoperative IOL position (ELP) based on
information of the 3-dimensional full shape of the crystalline lens, obtained
from quantitative eye anterior segment optical coherence tomography imaging. Real
patients were measured before and after cataract surgery (IOL implantation). The
IOL position and the postoperative refraction estimation errors were calculated
by subtracting the preoperative estimations from the actual values measured after
surgery. The proposed ELP formula produced lower estimation errors for both
parameters -ELP and refraction- than the predictions obtained with standard state
of-the-art methods, and opens new avenues to the development of new generation
IOL power calculation formulas that improve refractive and visual outcomes.
PMID- 29959388
TI - Noonan syndrome associated with growth hormone deficiency with biallelic LZTR1
variants.
PMID- 29959386
TI - Photophysical properties of cationic dyes captured in the mesoscale channels of
micron-sized metal-organic framework crystals.
AB - The optical properties of dye molecules in confined spaces can differ from the
solution phase due to confinement effects. Pre-organized mesoscale channels of
metal-organic frameworks (MOFs) are very suited for hosting various dyes, and the
robust frameworks often render the encapsulated dyes with certain preferential
geometries, which are different from those found in solution. Furthermore, pre
organized open channels can efficiently guide the uniform and unique spatial
distribution of dye molecules in a controlled manner, which are otherwise
difficult to achieve. Thus, sufficiently large dye molecules can avoid the
formation of complex aggregates when captured inside open channels. In contrast,
small dye molecules can form well-defined dimers or aggregates. The resulting dye
encapsulated MOFs can display unusual photophysical properties of the captured
dyes. An anionic framework of In-BTB with mesoscale 3D channels is utilized for
the efficient encapsulation of various cationic dyes through cation-exchange
processes. Six different cationic dyes are encapsulated in the anionic framework
of In-BTB, and their crystal structures are completely solved. Novel
photophysical properties of these spatially distributed dye molecules in dye@In
BTBs are investigated.
PMID- 29959387
TI - Age-related differences in humoral and cellular immune responses after primary
immunisation: indications for stratified vaccination schedules.
AB - Immunosenescence is characterised by reduced B and T cell responses. Evidence
shows that booster vaccinations are less effective in elderly people, but data on
the efficacy of primary immunisation are sparse. We conducted a monocentric, open
label, phase IV trial to compare immune responses to primary vaccinations using
the inactivated, adjuvanted Japanese Encephalitis vaccine by 30 elderly people
(mean 69, range 61-78 years) and 30 younger people (mean 24, range 18-30 years).
Humoral and cellular immune responses were analysed in relation to age and
cytomegalovirus (CMV) seropositivity. Vaccine-specific antibody titres were
significantly lower in elderly participants and 47% of them were non- or low
responders after the two doses of the vaccine neo-antigen. The reduced humoral
immune responses in elderly people correlated with reduced cytokine production,
such as interferon gamma (IFN-gamma) in vitro, as well as higher frequencies of
late-differentiated effector and effector memory T cells and T regulatory cells.
These cellular changes and lower antibody titres were particularly prominent in
CMV-seropositive elderly participants. If primary vaccination before the age of
60 is not possible, elderly patients may require different vaccination strategies
to ensure sufficient long-lasting immunity, such as adapted or accelerated
schedules and the use of different adjuvants.
PMID- 29959389
TI - Response to Nakaguma et al.
PMID- 29959390
TI - Creation of independently controllable multiple focal spots from segmented
Pancharatnam-Berry phases.
AB - Recently, based on space-variant Pancharatnam-Berry (PB) phases, various flat
devices allowing abrupt changes of beam parameters have been predicted and
demonstrated to implement intriguing manipulation on spin states in three
dimensions, including the efficient generation of vector beams, spin Hall effect
of light and light-guiding confinement, and so on. Here, we report on the
construction of independently controllable multiple focal spots with different
inhomogeneous polarization states by utilizing segmented PB phases. Combining the
phase shift approach with PB phases, we engineer fan-shaped segmented PB phases
and encode them onto two spin components that compose a hybrid polarized vector
beam in a modified common-path interferometer system. Experimental results
demonstrate that the fan-shaped segmented PB phase enables the flexible
manipulation of focal number, array structure and polarization state of each
focal spot. Furthermore, we demonstrate that this fan-shaped approach enables to
flexibly tailor the polarization state and the spin angular momentum distribution
of a tightly focused field, which have potential applications in optical
manipulation, tailored optical response and imaging etc.
PMID- 29959391
TI - Genetic Factors and Genotype-Environment Interactions Contribute to Variation in
Melanin Production in the Fungal Pathogen Cryptococcus neoformans.
AB - Cryptococcosis is a common opportunistic fungal infection that often disseminates
into the central nervous system, leading to meningitis. Production of melanin
pigments during infections is one of the most important virulence factors of its
causal agent, the human pathogenic yeast Cryptococcus neoformans species complex.
However, almost nothing is known about the patterns of variation in melanin
production among clinical and environmental strains and the potential effects of
such variations on virulence. In this study, we assembled a global collection of
C. neoformans var. neoformans strains and investigated their patterns of melanin
variation and potential contributors to such variations. Our analyses revealed
that genetic differences and genotype-environment interactions explained up to
59% and 43% of the population's melanin variance respectively, depending on the
tested environments. In comparison, environmental factors alone contributed
relatively little to melanin variance. We also identified specific changes within
the LAC1 gene, whose protein product catalyzes melanin synthesis, to be
associated with variable melanin levels. This study provides fresh insights into
the origin and evolution of virulence traits in fungal pathogens while
highlighting the complex interplay between genetic and environmental factors that
lead to phenotypic variance.
PMID- 29959393
TI - The struggle for stroke reclassification.
PMID- 29959392
TI - SLFN11: a new synthetic lethal target?
PMID- 29959394
TI - NREM sleep parasomnias as disorders of sleep-state dissociation.
AB - Non-rapid eye movement (NREM) sleep parasomnias (or NREM parasomnias) are
fascinating disorders with mysterious neurobiological substrates. These
conditions are common and often severe, with social, personal and forensic
implications. The NREM parasomnias include sleepwalking, sleep terrors and
confusional arousals - collectively termed disorders of arousal (DOAs) - as well
as less well-known entities such as sleep-related sexual behaviours and eating
disorders. Affected patients can exhibit waking behaviours arising abruptly out
of NREM sleep. Although the individual remains largely unresponsive to the
external environment, their EEG shows both typical sleep-like and wake-like
features, and they occasionally report dreaming afterwards. Therefore, these
disorders offer a unique natural model to explore the abnormal coexistence of
local sleep and wake brain activity and the dissociation between behaviour and
various aspects of consciousness. In this article, we critically review major
findings and updates on DOAs, focusing on neurophysiological studies, and offer
an overview of new clinical frontiers and promising future research areas. We
advocate a joint effort to inform clinicians and the general public about the
management and follow-up of these conditions. We also strongly encourage
collaborative multicentre studies to add more objective polysomnographic criteria
to the current official diagnostic definitions and to develop clinical practice
guidelines, multidisciplinary research approaches and evidence-based medical
care.
PMID- 29959396
TI - Azosemide is more potent than bumetanide and various other loop diuretics to
inhibit the sodium-potassium-chloride-cotransporter human variants hNKCC1A and
hNKCC1B.
AB - The Na+-K+-2Cl- cotransporter NKCC1 plays a role in neuronal Cl- homeostasis
secretion and represents a target for brain pathologies with altered NKCC1
function. Two main variants of NKCC1 have been identified: a full-length NKCC1
transcript (NKCC1A) and a shorter splice variant (NKCC1B) that is particularly
enriched in the brain. The loop diuretic bumetanide is often used to inhibit
NKCC1 in brain disorders, but only poorly crosses the blood-brain barrier. We
determined the sensitivity of the two human NKCC1 splice variants to bumetanide
and various other chemically diverse loop diuretics, using the Xenopus oocyte
heterologous expression system. Azosemide was the most potent NKCC1 inhibitor
(IC50s 0.246 uM for hNKCC1A and 0.197 uM for NKCC1B), being about 4-times more
potent than bumetanide. Structurally, a carboxylic group as in bumetanide was not
a prerequisite for potent NKCC1 inhibition, whereas loop diuretics without a
sulfonamide group were less potent. None of the drugs tested were selective for
hNKCC1B vs. hNKCC1A, indicating that loop diuretics are not a useful starting
point to design NKCC1B-specific compounds. Azosemide was found to exert an
unexpectedly potent inhibitory effect and as a non-acidic compound, it is more
likely to cross the blood-brain barrier than bumetanide.
PMID- 29959398
TI - Correction of center of rotation and projection angle in synchrotron X-ray
computed tomography.
AB - An error in tomographic reconstruction parameters can result considerable
artifacts in the reconstructed image, particularly in micro-computed tomography
and nano-computed tomography. This study involved designing an automatic method
for efficiently correcting errors resulting from incorrectly determined
rotational axes and projection angles. In this method, errors are corrected by
minimizing the "total variation" of a reconstructed image, and minimization is
accomplished by using the gradient descent method. Compared with two previous
methods, the proposed method achieved the best reconstruction results.
PMID- 29959397
TI - Crystallization of a human galectin-3 variant with two ordered segments in the
shortened N-terminal tail.
AB - Among members of the family of adhesion/growth-regulatory galectins, galectin-3
(Gal-3) bears a unique modular architecture. A N-terminal tail (NT) consisting of
the N-terminal segment (NTS) and nine collagen-like repeats is linked to the
canonical lectin domain. In contrast to bivalent proto- and tandem-repeat-type
galectins, Gal-3 is monomeric in solution, capable to self-associate in the
presence of bi- to multivalent ligands, and the NTS is involved in cellular
compartmentalization. Since no crystallographic information on Gal-3 beyond the
lectin domain is available, we used a shortened variant with NTS and repeats VII
IX. This protein crystallized as tetramers with contacts between the lectin
domains. The region from Tyr101 (in repeat IX) to Leu114 (in the CRD) formed a
hairpin. The NTS extends the canonical beta-sheet of F1-F5 strands with two new
beta-strands on the F face. Together, crystallographic and SAXS data reveal a
mode of intramolecular structure building involving the highly flexible Gal-3's
NT.
PMID- 29959399
TI - Impact of varying levels of hyperglycemia on clinicoradiographic outcomes after
endovascular reperfusion treatment.
AB - We evaluated the effects of admission hyperglycemia with different cut-off levels
on 3-month outcomes, infarct growth, and hemorrhagic transformation in acute
stroke patients with large artery occlusion of anterior circulation who received
endovascular treatment (EVT). Between January 2011 and May 2016, patients that
underwent EVT with pre-procedural and post-procedural diffusion-weighted imaging
were identified from a multicenter registry. Normoglycemia was defined as a
glucose level <= 110 mg/dL, moderate hyperglycemia as >110 and <=170 mg/dL, and
overt hyperglycemia as >170 mg/dL. Its effects on poor outcomes (3-month modified
Rankin Scale score 3-6), infarct growth, and parenchymal hematoma type 2 were
analyzed. Of 720 patients encountered, 341 patients were eligible. There was a
statistically significant difference in glycated hemoglobin levels between the
normoglycemia/moderate hyperglycemia and overt hyperglycemia groups (p < 0.001).
Moderate hyperglycemia (odds ratio 2.37 [95% confidence interval 1.26-4.45], p =
0.007) and overt hyperglycemia (2.84 [1.19-6.81], p = 0.019) were associated with
poor outcomes. Post-procedural infarct volumes were significantly greater in
hyperglycemic patients (padjusted = 0.003). Only overt hyperglycemia (9.28 [1.66
51.88], p = 0.011) was associated with parenchymal hematoma type 2. Overall
hyperglycemia was associated with poor outcomes and infarct growth, whereas overt
hyperglycemia was associated with parenchymal hematoma type 2.
PMID- 29959400
TI - Author Correction: Embryonic senescent cells re-enter cell cycle and contribute
to tissues after birth.
AB - The authors apologized for the spelling mistake of author name for Zhengyu Ju.
The correct form is Zhenyu Ju. We apologize for any hassle that may have been
caused by our mistake.
PMID- 29959402
TI - Lipid droplets from the inside.
PMID- 29959401
TI - Exosomal PD-L1 harbors active defense function to suppress T cell killing of
breast cancer cells and promote tumor growth.
PMID- 29959403
TI - The airway inflammation induced by nasal inoculation of PM2.5 and the treatment
of bacterial lysates in rats.
AB - Particulate matter (PM) is one of the most important environmental issues in
China. This study aimed to explore the correlation between PM2.5 and airway
inflammation in healthy rats. The PM2.5 group was given an intranasal
instillation of PM2.5 suspension on 15 consecutive days, and each received oral
saline from day 16 to 90. The BV intervention group was treated as the PM2.5
exposure group, except that BV instead of saline was given daily. A
histopathologic examination was performed to evaluate the airway inflammation.
The prevalence and function of Th1/Th2/Treg/Th17 cells were detected by flow
cytometry and ELISA. The expression of AhR was detected by western blot and real
time PCR. We found that epithelial damage and increased infiltration of
inflammatory cell were present in the airways after PM2.5 exposure; there was an
immune imbalance of Th cells in the PM2.5 group; the expression of AhR was
increased in the airways after PM2.5 exposure. In the PM2.5 + BV group, we
demonstrated alleviated immune imbalance and reduced inflammatory cell
infiltration in the airways. Our study showed that exposure to PM2.5 induced
airway inflammation. The imbalance of Th1/Th2/Treg/Th17 in PM2.5-induced airway
inflammation might be associated with activation of the AhR pathway. Oral BV
reduces PM2.5-induced airway inflammation and regulates systemic immune responses
in rats.
PMID- 29959404
TI - Dpp regulates autophagy-dependent midgut removal and signals to block ecdysone
production.
AB - Animal development and homeostasis require the programmed removal of cells.
Autophagy-dependent cell deletion is a unique form of cell death often involved
in bulk degradation of tissues. In Drosophila the steroid hormone ecdysone
controls developmental transitions and triggers the autophagy-dependent removal
of the obsolete larval midgut. The production of ecdysone is exquisitely
coordinated with signals from numerous organ systems to mediate the correct
timing of such developmental programs. Here we report an unexpected role for the
Drosophila bone morphogenetic protein/transforming growth factor beta ligand,
Decapentaplegic (Dpp), in the regulation of ecdysone-mediated midgut degradation.
We show that blocking Dpp signaling induces premature autophagy, rapid cell
death, and midgut degradation, whereas sustained Dpp signaling inhibits autophagy
induction. Furthermore, Dpp signaling in the midgut prevents the expression of
ecdysone responsive genes and impairs ecdysone production in the prothoracic
gland. We propose that Dpp has dual roles: one within the midgut to prevent
improper tissue degradation, and one in interorgan communication to coordinate
ecdysone biosynthesis and developmental timing.
PMID- 29959405
TI - Modeling and mapping the burden of disease in Kenya.
AB - Precision public health approaches are crucial for targeting health policies to
regions most affected by disease. We present the first sub-national and spatially
explicit burden of disease study in Africa. We used a cross-sectional study
design and assessed data from the Kenya population and housing census of 2009 for
calculating YLLs (years of life lost) due to premature mortality at the division
level (N = 612). We conducted spatial autocorrelation analysis to identify
spatial clusters of YLLs and applied boosted regression trees to find statistical
associations between locational risk factors and YLLs. We found statistically
significant spatial clusters of high numbers of YLLs at the division level in
western, northwestern, and northeastern areas of Kenya. Ethnicity and household
crowding were the most important and significant risk factors for YLL. Further
positive and significantly associated variables were malaria endemicity, northern
geographic location, and higher YLL in neighboring divisions. In contrast, higher
rates of married people and more precipitation in a division were significantly
associated with less YLL. We provide an evidence base and a transferable approach
that can guide health policy and intervention in sub-national regions afflicted
by disease burden in Kenya and other areas of comparable settings.
PMID- 29959406
TI - Trait-based patterns of microbial dynamics in dormancy potential and
heterotrophic strategy: case studies of resource-based and post-press succession.
AB - Understanding the relationship between microbial community structure and function
is a major challenge in microbial ecology. Recent work has shown that community
weighted mean 16S rRNA gene copies, as a proxy for heterotrophic growth strategy,
is a microbial community trait that decreases predictably over successional
trajectories that are underpinned by changes in resource availability. However,
it has been challenging to identify other microbial traits that are predictive of
community functions and have consistent patterns with succession. Trait-based
patterns of secondary succession (e.g., after a disturbance) are less often
considered, and these responses may be underpinned by abiotic drivers other than
changes in resources. In this perspectives piece, we present hypotheses about
microbial traits important for microbial succession in resource-based and post
press disturbance scenarios, as synthesized from previous works and extended
within this work. Using four case studies, we compare two traits, heterotrophic
strategy and dormancy potential, and two different types of succession, resource
based (endogenous heterotrophic) and post-press. There were decreases in weighted
ribosomal operon counts and in dormancy genes over resource-based succession.
Both traits also were lower in post-press succession as compared to reference
conditions, but increased with time from disturbance. Thus, dormancy potential
may be an additional trait that changes predictably with succession. Finally,
considering changes in microbial community traits over post-press succession is
as important as over resource-based succession. These patterns need to be
interpreted carefully and reference and recovering samples can be collected to
improve interpretation of changes in community traits over post-press succession.
PMID- 29959407
TI - Visualization of solute diffusion into cell walls in solution-impregnated wood
under varying relative humidity using time-of-flight secondary ion mass
spectrometry.
AB - The purpose of the present study is to clarify the diffusion of non-volatile
substances into cell walls during the conditioning procedure under varying
relative humidities (RH). In this paper, wood blocks were impregnated using an
aqueous solution of melamine formaldehyde (MF), and they were subsequently
conditioned under RHs of 11, 43, and 75%. The solute that diffused into the cell
walls was visualized using time-of-flight secondary ion mass spectrometry (TOF
SIMS). The volumetric relative swelling of the samples during the conditioning
procedure was calculated. The results showed increased cell wall swelling at
higher RH, which may have been caused by higher MF diffusion into the cell walls
and/or higher moisture content. Cryo-TOF-SIMS measurements showed that more cell
cavities were unfilled with MF at higher RH, indicating that most of the MF
diffused from the cell cavities into the cell walls. The relative intensity of MF
in the cell walls of the cured samples was evaluated from dry-TOF-SIMS images,
which showed a higher relative intensity of MF in the cell walls at higher RH.
With the ability to visualize and semi-quantitatively evaluate the solute in cell
walls, TOF-SIMS will serve as a powerful tool for future studies of solute
diffusion mechanisms in solution-impregnated wood.
PMID- 29959409
TI - A molecular signature for social isolation identified in the brain.
PMID- 29959408
TI - Mechanistic insights into the augmented effect of bone marrow mesenchymal stem
cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic
rats.
AB - This study was designed to assess whether the protective effects of bone marrow
derived mesenchymal stem cells (MSCs) against diabetes could be enhanced by
pioglitazone (PIO), a PPARgamma agonist. Combined MSCs and PIO treatments
markedly improved fasting blood glucose, body weight, lipid profile levels,
insulin level, insulin resistance, beta cell function. Those protective effects
also attenuated both pancreatic lesions and fibrosis in diabetic rats and
decreased the depletion of pancreatic mediators of glycemic and lipid metabolism
including peroxisome proliferator-activated receptor alpha (PPARalpha), PGC
1alpha, GLP-1 and IRS-2. Cardiac biogenesis of diabetic groups was also improved
with MSCs and/or PIO treatments as reflected by the enhanced up-regulation of the
expressions of cardiac IRS1, Glucose transporter 4, PGC-1, PPARalpha and CPT-1
genes and the down-regulated expression of lipogenic gene SREBP. The combination
of MSCs and PIO also potentiated the decrease of abnormal myocardial pathological
lesions in diabetic rats. Similarly, the inhibitory effects of MSCs on diabetic
cardiac fibrosis and on the up regulations of TGF-beta, collagen I and III gene
expressions were partial but additive when combined with PIO. Therefore, combined
therapy with PIO and BMCs transplantation could further potentiate the protective
benefit of MSCs against diabetes and cardiac damage compared to MSCs monotherapy.
PMID- 29959410
TI - Unexpected cell population gives fat a brake.
PMID- 29959411
TI - Actin proteins assemble to protect the genome.
PMID- 29959412
TI - Light Emitting Diodes based Photoacoustic Imaging and Potential Clinical
Applications.
AB - Using low cost and small size light emitting diodes (LED) as the alternative
illumination source for photoacoustic (PA) imaging has many advantages, and can
largely benefit the clinical translation of the emerging PA imaging technology.
Here, we present our development of LED-based PA imaging integrated with B-mode
ultrasound. To overcome the challenge of achieving sufficient signal-to-noise
ratio by the LED light that is orders of magnitude weaker than lasers, extensive
signal averaging over hundreds of pulses is performed. Facilitated by the fast
response of the LED and the high-speed driving as well as the high pulse
repetition rate up to 16 kHz, B-mode PA images superimposed on gray-scale
ultrasound of a biological sample can be achieved in real-time with frame rate up
to 500 Hz. The LED-based PA imaging could be a promising tool for several
clinical applications, such as assessment of peripheral microvascular function
and dynamic changes, diagnosis of inflammatory arthritis, and detection of head
and neck cancer.
PMID- 29959413
TI - Bortezomib-based induction therapy with high or low-dose dexamethasone in newly
diagnosed, transplant-eligible multiple myeloma.
PMID- 29959414
TI - Discriminating a common somatic ASXL1 mutation (c.1934dup; p.G646Wfs*12) from
artifact in myeloid malignancies using NGS.
PMID- 29959415
TI - A non-myeloablative conditioning approach for long-term engraftment of human and
mouse hematopoietic stem cells.
PMID- 29959416
TI - Nitrogen loading effects on nitrification and denitrification with functional
gene quantity/transcription analysis in biochar packed reactors at 5 degrees C.
AB - This study investigated the nitrogen transformation rates of different nitrogen
loading (20, 30, and 50 mg TN/L) biochar packed reactors (C:N:P = 100:5:1) within
125 days at 5 degrees C. The results showed that high nitrogen loading resulted
in an NH4+ (TN) removal efficiency decline from 98% (57%) to 83% (29%), with
biochar yielding a higher NH4+, TN and DON removal rate than conventional
activated sludge. Moreover, all biochar packed reactors realized a quick start-up
by dropping in temperature stage by stage, and the effluent dissolved organic
nitrogen (DON) concentrations of R20, R30, and R50 were 0.44 +/- 0.18, 0.85 +/-
0.35, and 0.66 +/- 0.26 mg/L, respectively. The nirS/amoA, nxrA/amoA, and
amoA/(narG + napA) were deemed to be the markers of ammonium oxidation rate
(SAOR), specific nitrite oxidation rate (SNOR), and specific nitrate reduction
rate (SNRR), respectively. Compared with functional gene quantity data,
transcription data (mRNA) introduced into stepwise regression analyses agreed
well with nitrogen transformation rates. High nitrogen loading also resulted in
the cell viability decreased in R50. Nitrogen loadings and operation time both
led to a significant variation in cell membrane composition, and unsaturated
fatty acids (UFAs) significantly increased in R30 (46.49%) and R50 (36.34%). High
throughput sequencing revealed that nitrogen loadings increased the abundance of
nitrifying bacteria (e.g., Nitrospira) and reduced the abundance of denitrifying
bacteria (e.g., Nakamurella, Thermomonas, and Zoogloea) through linear
discriminant analysis (LDA).
PMID- 29959418
TI - Characterization of a murine nonalcoholic steatohepatitis model induced by high
fat high calorie diet plus fructose and glucose in drinking water.
AB - There are varieties of murine models of nonalcoholic steatohepatitis (NASH) with
different pathophysiologic characteristics. For preclinical assessment, a
standardized model would allow comparisons of various pharmacotherapeutic
candidates in efficacy, pharmacokinetics, pharmaco-metabolism, and adverse
effects under a same system. The present study aims to characterize murine NASH
models by comparing end-points of major abnormalities. NASH was induced by
feeding high fructose/glucose in drinking water (HF/G), high-fat/calorie diet
(HFCD), and in combination (HFCD-HF/G) in mice for 8 or 16 weeks. HF/G feeding
caused a minimal fat accumulation and increase in free fatty acids (FFA). In
contrast, HFCD-HF/G feeding resulted in a remarkable increase in body weight,
subcutaneous and visceral adipose tissue, macrosteatosis with a nearly seven-fold
increase in triglyceride and FFA content, accompanied with marked hepatocellular
injury, inflammatory responses, fibrosis, and insulin resistance, and represented
as typical NASH in histopathology, metabolic, and adipokine profiles in a
progressive manner. Meanwhile, mice fed HFCD displayed significant steatosis,
necroptosis, fibrosis, insulin resistance, metabolic, and adipokine profiles, and
the extent is less than those fed HFCD-HF/G. Significant MCP-1, CCR-2, and NLRP
1/3 activation were found in mice fed HFCD and HFCD-HF/G for 16 weeks, whereas
gene expression of CPT-1 and ACOX-1 was down-regulated in these two groups in
comparison to the controls. Nuclear receptors, such as SREBP-1c, FXR, LXR-alpha,
PPAR-alpha, and PPAR-gamma, were strikingly elevated in the HFCD-HF/G group. In
conclusion, feeding HFCD-HF/G resulted in a reliable NASH model in mice with
remarkable necroptosis, steatosis, fibrosis, and insulin resistance as well as a
disordered profile of lipid metabolism and adipokine, and HFCD caused significant
NASH features in histopathology and metabolic profiles only at a late stage.
Whereas HF/G feeding barely led to minimal fat accumulation, some changes at
molecular levels and metabolic disturbance in mice.
PMID- 29959419
TI - High-mobility group box 1 induces endoplasmic reticulum stress and activates
hepatic stellate cells.
AB - Liver fibrosis is a worldwide clinical issue. The activation of hepatic stellate
cells (HSCs) is the central event during the hepatic fibrotic response. However,
the exact mechanisms related to HSC activation and the connection between
hepatocytes and HSCs remain unclear. We elucidated the mechanism by which the
nuclear-damage-associated molecular pattern molecule, high-mobility group box 1
(HMGB1) was released from the impaired hepatocytes and induced endoplasmic
reticulum stress to activate HSCs. In this work, we demonstrated that HMGB1 can
be released from hepatocytes and the released HMGB1 activates the HSCs via ER
stress at the transcriptional level which was dependent on the activation of both
the TLR4 and RAGE signaling pathways rather than the TLR2 signaling pathway.
HMGB1 induction of proinflammatory cytokines interleukin (IL)-1beta and IL-18
release was dependent on ER stress. In vivo, stable inhibition of HMGB1
suppressed liver fibrosis. These results suggest that under damage condition,
HMGB1 can be secreted from injured hepatocytes and activates TLR4- and RAGE
signaling pathways to induce ER stress which activates HSCs. Moreover, HMGB1 can
produce multiple inflammatory mediators through ER stress, which, in turn,
promote liver fibrosis.
PMID- 29959417
TI - Inflammatory mediators reduce surface PrPc on human BMVEC resulting in decreased
barrier integrity.
AB - The cellular prion protein (PrPc) is a surface adhesion molecule expressed at
junctions of various cell types including brain microvascular endothelial cells
(BMVEC) that are important components of the blood-brain barrier (BBB). PrPc is
involved in several physiological processes including regulation of epithelial
cell barrier function and monocyte migration across BMVEC. BBB dysfunction and
disruption are significant events in central nervous system (CNS) inflammatory
processes including HIV neuropathogenesis. Tumor necrosis factor (TNF)-alpha and
vascular endothelial growth factor (VEGF) are two inflammatory factors that have
been implicated in the processes that affect BBB integrity. To examine the effect
of inflammation on PrPc expression in BMVEC, we used these mediators and found
that TNF-alpha and VEGF decrease surface PrPc on primary human BMVEC. We also
showed that these factors decrease total PrPc protein as well as mRNA, indicating
that they regulate expression of this protein by de novo synthesis. To determine
the effect of PrPc loss from the surface of BMVEC on barrier integrity, we used
small hairpin RNAs to knockdown PrPc. We found that the absence of PrPc from
BMVEC causes increased permeability as determined by a fluorescein isothiocyanate
(FITC)-dextran permeability assay. This suggests that cell surface PrPc is
essential for endothelial monolayer integrity. To determine the mechanism by
which PrPc downregulation leads to increased permeability of an endothelial
monolayer, we examined changes in expression and localization of tight junction
proteins, occludin and claudin-5, and found that decreased PrPc leads to
decreased total and membrane-associated occludin and claudin-5. We propose that
an additional mechanism by which inflammatory factors affect endothelial
monolayer permeability is by decreasing cell-associated PrPc. This increase in
permeability may have subsequent consequences that lead to CNS damage.
PMID- 29959420
TI - Osteopontin isoforms differentially promote arteriogenesis in response to
ischemia via macrophage accumulation and survival.
AB - Osteopontin (OPN) is critical for ischemia-induced neovascularization. Unlike
rodents, humans express three OPN isoforms (a, b, and c); however, the roles of
these isoforms in post-ischemic neovascularization and cell migration remain
undefined. Our objective was to determine if OPN isoforms differentially affect
post-ischemic neovascularization and to elucidate the mechanisms underlying these
differences. To investigate if human OPN isoforms exert divergent effects on post
ischemic neovascularization, we utilized OPN-/- mice and a loss-of-function/gain
of-function approach in vivo and in vitro. In this study OPN-/- mice underwent
hindlimb ischemia surgery and 1.5 * 106 lentivirus particles were administered
intramuscularly to overexpress OPNa, OPNb, or OPNc. OPNa and OPNc significantly
improved limb perfusion 30.4% +/- 0.8 and 70.9% +/- 6.3, respectively, and this
translated to improved functional limb use, as measured by voluntary running
wheel utilization. OPNa- and OPNc-treated animals exhibited significant increases
in arteriogenesis, defined here as the remodeling of existing arterioles into
larger conductance arteries. Macrophages play a prominent role in the
arteriogenesis process and OPNa- and OPNc-treated animals showed significant
increases in macrophage accumulation in vivo. In vitro, OPN isoforms did not
affect macrophage polarization, whereas all three isoforms increased macrophage
survival and decreased macrophage apoptosis. However, OPN isoforms exert
differential effects on macrophage migration, where OPNa and OPNc significantly
increased macrophage migration, with OPNc serving as the most potent isoform. In
conclusion, human OPN isoforms exert divergent effects on neovascularization
through differential effects on arteriogenesis and macrophage accumulation in
vivo and on macrophage migration and survival, but not polarization, in vitro.
Altogether, these data support that human OPN isoforms may represent novel
therapeutic targets to improve neovascualrization and preserve tissue function in
patients with obstructive artery diseases.
PMID- 29959421
TI - Nuclear shape and orientation features from H&E images predict survival in early
stage estrogen receptor-positive breast cancers.
AB - Early-stage estrogen receptor-positive (ER+) breast cancer (BCa) is the most
common type of BCa in the United States. One critical question with these tumors
is identifying which patients will receive added benefit from adjuvant
chemotherapy. Nuclear pleomorphism (variance in nuclear shape and morphology) is
an important constituent of breast grading schemes, and in ER+ cases, the grade
is highly correlated with disease outcome. This study aimed to investigate
whether quantitative computer-extracted image features of nuclear shape and
orientation on digitized images of hematoxylin-stained and eosin-stained tissue
of lymph node-negative (LN-), ER+ BCa could help stratify patients into discrete
(<10 years short-term vs. >10 years long-term survival) outcome groups
independent of standard clinical and pathological parameters. We considered a
tissue microarray (TMA) cohort of 276 ER+, LN- patients comprising 150 patients
with long-term and 126 patients with short-term overall survival, wherein 177
randomly chosen cases formed the modeling set, and 99 remaining cases the test
set. Segmentation of individual nuclei was performed using multiresolution
watershed; subsequently, 615 features relating to nuclear shape/texture and
orientation disorder were extracted from each TMA spot. The Wilcoxon's rank-sum
test identified the 15 most prognostic quantitative histomorphometric features
within the modeling set. These features were then subsequently combined via a
linear discriminant analysis classifier and evaluated on the test set to assign a
probability of long-term vs. short-term disease-specific survival. In univariate
survival analysis, patients identified by the image classifier as high risk had
significantly poorer survival outcome: hazard ratio (95% confident interval) =
2.91(1.23-6.92), p = 0.02786. Multivariate analysis controlling for T-stage,
histology grade, and nuclear grade showed the classifier to be independently
predictive of poorer survival: hazard ratio (95% confident interval) = 3.17(0.33
30.46), p = 0.01039. Our results suggest that quantitative histomorphometric
features of nuclear shape and orientation are strongly and independently
predictive of patient survival in ER+, LN- BCa.
PMID- 29959422
TI - Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol
intake in epidemiological studies.
AB - The accurate assessment of dietary intake is crucial to investigate the effect of
diet on health. Currently used methods, relying on self-reporting and food
composition data, are known to have limitations and might not be suitable to
estimate the intake of many bioactive food components. An alternative are
nutritional biomarkers, which can allow an unbiased assessment of intake. They
require a careful evaluation of their suitability, including: (a) the
availability of a precise, accurate and robust analytical method, (b) their
specificity (c) a consistent relationship with actual intake. We have evaluated
human metabolites of a microbiome-derived flavan-3-ol catabolite, 5-(3',4'
dihydroxyphenyl)-[gamma]-valerolactone (gVL), as biomarker of flavan-3-ol intake
in large epidemiological studies. Flavan-3-ols are widely consumed plant
bioactives, which have received considerable interest due to their potential
ability to reduce CVD risk. The availability of authentic standards allowed the
development of a validated high-throughput method suitable for large-scale
studies. In dietary intervention studies, we could show that gVL metabolites are
specific for flavan-3-ols present in tea, fruits, wine and cocoa-derived
products, with a strong correlation between intake and biomarker (Spearman's r =
0.90). This biomarker will allow for the first time to estimate flavan-3-ol
intake and further investigation of associations between intake and disease risk.
PMID- 29959423
TI - High pressure minerals in the Chateau-Renard (L6) ordinary chondrite:
implications for collisions on its parent body.
AB - We report the first discoveries of high-pressure minerals in the historical L6
chondrite fall Chateau-Renard, based on co-located Raman spectroscopy, scanning
electron microscopy (SEM) with energy-dispersive X-ray spectroscopy and electron
backscatter diffraction, electron microprobe analysis, and transmission electron
microscopy (TEM) with selected-area electron diffraction. A single polished
section contains a network of melt veins from ~40 to ~200 MUm wide, with no cross
cutting features requiring multiple vein generations. We find high-pressure
minerals in veins greater than ~50 MUm wide, including assemblages of ringwoodite
+ wadsleyite, ringwoodite + wadsleyite + majorite-pyropess, and ahrensite +
wadsleyite. In association with ahrensite + wadsleyite at both SEM and TEM scale,
we find a sodic pyroxene whose Raman spectrum is indistinguishable from that of
jadeite but whose composition and structure are those of omphacite. We discuss
constraints on the impact record of this meteorite and the L-chondrites in
general.
PMID- 29959424
TI - Prognostic value of clinical and radiological findings for conservative treatment
of idiopathic ulnar impaction syndrome.
AB - Ulnar impaction syndrome (UIS) is a common source of ulnar-sided wrist pain, yet
not all cases of radiographic ulnar impaction are symptomatic. We retrospectively
analyze clinical or radiologic factors that affect prognoses of conservative
treatment for idiopathic UIS. A total of 114 patients who had been diagnosed with
UIS were treated with 6 weeks of short arm orthosis followed by formal
physiotherapy for 6 weeks, with lifestyle modification to limit aggravating
movements. The response to treatment, including pain numeric rating scale on an
ulnar provocation test, grip strength, Disability of the Arm, Shoulder, and Hand
score (DASH), was assessed at 24-week follow-up. For the 24-week follow-up, 29
patients (25%) underwent ulnar shortening osteotomy due to persistent symptoms
after conservative treatment, and 18 (16%) patients had pain scores of greater
than 5, but they had not undergone surgery. After controlling for confounding
variables, female gender (odds ratio (OR) 1.39), duration of symptom (OR 1.27),
high pain NRS score on provocation test (OR 1.45), and enhanced carpal or distal
ulna bone on MRI (OR 1.82) were associated with a higher likelihood of treatment
failure. Knowledge of the factors offers physicians insight into predicting
prognoses and helps patients set realistic expectations.
PMID- 29959425
TI - Thermal blanketing by ivy (Hedera helix L.) can protect building stone from
damaging frosts.
AB - The impact of plants growing on buildings remains controversial, especially for
vulnerable historic walls and ruins requiring on-going conservation. English ivy
(Hedera helix L.) can cause considerable damage where it is able to grow into
deteriorating masonry, yet in some circumstances it may be protective. Here we
focus on the potential of ivy to buffer damaging thermal cycles and frost events
that can contribute to the deterioration of masonry materials. On limestone
masonry test walls in central Southern England (Wytham near Oxford, UK), ivy
foliage had a significant influence on stone-surface freezing regimes. Over two
successive winters (2012/13 and 2013/14) the frequency of freezing events under
ivy was reduced on average by 26%, their duration by 34% and their severity by
32%. A subsequent laboratory simulation showed that stone mass loss, surface
softening, and textural development were all significantly reduced under an 'ivy
covered' thermal regime. Cautious extrapolation indicates that ivy can reduce
frost-driven granular-scale decay of limestone by the order of 30 g m-2 yr-1,
depending on the local freezing regime. Whilst the capacity of ivy to cause
damage should not be underplayed, vertical greenery can aid heritage conservation
efforts by mitigating specific environmental threats.
PMID- 29959426
TI - Evolution of MHC class I genes in Eurasian badgers, genus Meles (Carnivora,
Mustelidae).
AB - Because of their role in immune defense against pathogens, major
histocompatibility complex (MHC) genes are useful in evolutionary studies on how
wild vertebrates adapt to their environments. We investigated the molecular
evolution of MHC class I (MHCI) genes in four closely related species of Eurasian
badgers, genus Meles. All four species of badgers showed similarly high variation
in MHCI sequences compared to other Carnivora. We identified 7-21 putatively
functional MHCI sequences in each of the badger species, and 2-7 sequences per
individual, indicating the existence of 1-4 loci. MHCI exon 2 and 3 sequences
encoding domains alpha1 and alpha2 exhibited different clade topologies in
phylogenetic networks. Non-synonymous nucleotide substitutions at codons for
antigen-binding sites exceeded synonymous substitutions for domain alpha1 but not
for domain alpha2, suggesting that the domains alpha1 and alpha2 likely had
different evolutionary histories in these species. Positive selection and
recombination seem to have shaped the variation in domain alpha2, whereas
positive selection was dominant in shaping the variation in domain alpha1. In the
separate phylogenetic analyses for exon 2, exon 3, and intron 2, each showed
three clades of Meles alleles, with rampant trans-species polymorphism,
indicative of the long-term maintenance of ancestral MHCI polymorphism by
balancing selection.
PMID- 29959427
TI - The sperm factor: paternal impact beyond genes.
AB - The fact that sperm carry more than the paternal DNA has only been discovered
just over a decade ago. With this discovery, the idea that the paternal condition
may have direct implications for the fitness of the offspring had to be
revisited. While this idea is still highly debated, empirical evidence for
paternal effects is accumulating. Male condition not only affects male fertility
but also offspring early development and performance later in life. Several
factors have been identified as possible carriers of non-genetic information, but
we still know little about their origin and function and even less about their
causation. I consider four possible non-mutually exclusive adaptive and non
adaptive explanations for the existence of paternal effects in an evolutionary
context. In addition, I provide a brief overview of the main non-genetic
components found in sperm including DNA methylation, chromatin modifications,
RNAs and proteins. I discuss their putative functions and present currently
available examples for their role in transferring non-genetic information from
the father to the offspring. Finally, I identify some of the most important open
questions and present possible future research avenues.
PMID- 29959429
TI - Dad's diet - smRNA methylation signatures in sperm pass on disease risk.
PMID- 29959428
TI - Evolution without standing genetic variation: change in transgenerational plastic
response under persistent predation pressure.
AB - Transgenerational phenotypic plasticity is a fast non-genetic response to
environmental modifications that can buffer the effects of environmental stresses
on populations. However, little is known about the evolution of plasticity in the
absence of standing genetic variation although several non-genetic inheritance
mechanisms have now been identified. Here we monitored the pea aphid
transgenerational phenotypic response to ladybird predators (production of winged
offspring) during 27 generations of experimental evolution in the absence of
initial genetic variation (clonal multiplication starting from a single
individual). We found that the frequency of winged aphids first increased rapidly
in response to predators and then remained stable over 25 generations, implying a
stable phenotypic reconstruction at each generation. We also found that the high
frequency of winged aphids persisted for one generation after removing predators.
Winged aphid frequency then entered a refractory phase during which it dropped
below the level of control lines for at least two generations before returning to
it. Interestingly, the persistence of the winged phenotype decreased and the
refractory phase lasted longer with the increasing number of generations of
exposure to predators. Finally, we found that aphids continuously exposed to
predators for 22 generations evolved a significantly weaker plastic response than
aphids never exposed to predators, which, in turn, increased their fitness in
presence of predators. Our findings therefore showcased an example of
experimental evolution of plasticity in the absence of initial genetic variation
and highlight the importance of integrating several components of non-genetic
inheritance to detect evolutionary responses to environmental changes.
PMID- 29959431
TI - Geographic variation and plasticity in climate stress resistance among southern
African populations of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae).
AB - Traits of thermal sensitivity or performance are typically the focus of species
distribution modelling. Among-population trait variation, trait plasticity,
population connectedness and the possible climatic covariation thereof are seldom
accounted for. Here, we examine multiple climate stress resistance traits, and
the plasticity thereof, for a globally invasive agricultural pest insect, the
Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae).
We also accounted for body size and population genetic connectivity among
distinct populations from diverse bioclimatic regions across southern Africa.
Desiccation resistance, starvation resistance, and critical thermal minimum
(CTmin) and maximum (CTmax) of C. capitata varied between populations. For
thermal tolerance traits, patterns of flexibility in response to thermal
acclimation were suggestive of beneficial acclimation, but this was not the case
for desiccation or starvation resistance. Population differences in measured
traits were larger than those associated with acclimation, even though gene flow
was high. Desiccation resistance was weakly but positively affected by growing
degree-days. There was also a weak positive relationship between CTmin and
temperature seasonality, but CTmax was weakly but negatively affected by the same
bioclimatic variable. Our results suggest that the invasive potential of C.
capitata may be supported by adaptation of tolerance traits to local bioclimatic
conditions.
PMID- 29959430
TI - Diagnosis and management of pseudohypoparathyroidism and related disorders: first
international Consensus Statement.
AB - This Consensus Statement covers recommendations for the diagnosis and management
of patients with pseudohypoparathyroidism (PHP) and related disorders, which
comprise metabolic disorders characterized by physical findings that variably
include short bones, short stature, a stocky build, early-onset obesity and
ectopic ossifications, as well as endocrine defects that often include resistance
to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and
its related disorders vary between affected individuals with considerable
clinical and molecular overlap between the different types. A specific diagnosis
is often delayed owing to lack of recognition of the syndrome and associated
features. The participants in this Consensus Statement agreed that the diagnosis
of PHP should be based on major criteria, including resistance to PTH, ectopic
ossifications, brachydactyly and early-onset obesity. The clinical and laboratory
diagnosis should be confirmed by a molecular genetic analysis. Patients should be
screened at diagnosis and during follow-up for specific features, such as PTH
resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal
deformities, oral health, weight gain, glucose intolerance or type 2 diabetes
mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic
ossifications and neurocognitive impairment. Overall, a coordinated and
multidisciplinary approach from infancy through adulthood, including a transition
programme, should help us to improve the care of patients affected by these
disorders.
PMID- 29959432
TI - S100B immunization triggers NFkappaB and complement activation in an autoimmune
glaucoma model.
AB - In glaucoma, latest studies revealed an involvement of the complement system with
and without an elevated intraocular pressure. In the experimental autoimmune
glaucoma model, immunization with antigens, such as S100B, lead to retinal
ganglion cell (RGC) loss and optic nerve degeneration after 28 days. Here, we
investigated the timeline of progression of the complement system, toll-like
receptor 4 (TLR4), and the transcription factor nucleus factor-kappa B
(NFkappaB). Therefore, rats were immunized with S100B protein (S100) and analyzed
at 3, 7, and 14 days. RGC numbers were comparable at all points in time, whereas
a destruction of S100 optic nerves was noted at 14 days. A significant increase
of mannose binding lectin (MBL) was observed in S100 retinas at 3 days.
Subsequently, significantly more MBL+ cells were seen in S100 optic nerves at 7
and 14 days. Accordingly, C3 was upregulated in S100 retinas at 14 days. An
increase of interleukin-1 beta was noted in S100 aqueous humor samples at 7 days.
In this study, activation of complement system via the lectin pathway was
obvious. However, no TLR4 alterations were noted in S100 retinas and optic
nerves. Interestingly, a significant NFkappaB increase was observed in S100
retinas at 7 and 14 days. We assume that NFkappaB activation might be triggered
via MBL leading to glaucomatous damage.
PMID- 29959433
TI - Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor
activity in spinal cord injured rats: introduction of an alternative therapy.
AB - STUDY DESIGN: This is an animal study. OBJECTIVES: Metformin is a safe drug for
controlling blood sugar in diabetes. It has been shown that metformin improves
locomotor recovery after spinal cord injury (SCI). Neuropathic pain is also a
disturbing component of SCI. It is indicated that metformin has neuroprotective
and anti-inflammatory effects, which attenuate neuropathic pain and hyperalgesia
in injured nerves. Thus, we evaluated metformin's therapeutic effects on SCI
neuroinflammation and its sensory and locomotor complications. Meanwhile, results
were compared to minocycline, an anti-neuroinflammation therapy in SCI. SETTING:
Experimental Medicine Research Center, Tehran University of Medical Sciences,
Iran METHODS: In an animal model of SCI, 48 male rats were subjected to T9
vertebra laminectomy. Animals were divided into a SHAM-operated group and five
treatment groups. The treatments included normal saline as a vehicle control
group, minocycline 90 mg/kg and metformin at the doses of 10, 50 and 100 mg/kg.
Locomotor scaling, behavioral tests for neuropathic pain and weight changes were
evaluated and compared through a 28-days period. At the end of the study, tissue
samples were taken to assess neuroinflammatory changes. RESULTS: Metformin 50
mg/kg improved the locomotors ability (p < 0.001) and decreased sensitivity to
mechanical and thermal allodynia (p < 0.01). These results were compatible with
minocycline effect on SCI (p > 0.05). While metformin led to weight loss, both
metformin and minocycline significantly decreased neuroinflammation in the
assessment of cord tissue histopathology, and levels of TNF-alpha and interleukin
1beta (p < 0.001). CONCLUSIONS: Metformin could be considered as an alternative
therapeutic agent for SCI, as it potentially attenuates neuroinflammation,
sensory and locomotor complications of cord injury.
PMID- 29959434
TI - The extent of extra-axonal tissue damage determines the levels of CSPG
upregulation and the success of experimental axon regeneration in the CNS.
AB - The failure of mature central nervous system (CNS) projection neurons to
regenerate axons over long distances drastically limits the recovery of functions
lost after various CNS injuries and diseases. Although a number of manipulations
that stimulate some degree of axon regeneration that overcomes the inhibitory
environment after CNS injury have been discovered, the extent of regeneration
remains very limited, emphasizing the need for improved therapies. Regenerating
axons need nerve tissue environment capable of supporting their growth, and
severe extra-axonal tissue damage and remodeling after injury may disrupt such
environment. Here, we used traumatic injury to the mouse optic nerve as a model
system to investigate how the extent of extra-axonal tissue damage affects
experimental axon regeneration. Axon regeneration was stimulated by the shRNA
mediated knockdown (KD) of Pten gene expression in the retinal ganglion cells,
and the extent of extra-axonal tissue damage was varied by changing the duration
of optic nerve crush. Although no axons were spared using either 1 or 5 seconds
crush, we found that Pten KD-stimulated axon regeneration was significantly
reduced in 5 seconds compared with 1 second crush. The more severe extra-axonal
tissue damage did not cause tissue atrophy, but led to significantly higher
upregulation of axon growth-inhibiting chondroitin sulfate proteoglycan (CSPG) in
the glial scar and also enlarged glial scar size, compared with less severely
damaged tissue. Thus, the success of axon-regenerating approaches that target
neuronal intrinsic mechanisms of axon growth is dependent on the preservation of
appropriate extra-axonal tissue environment, which may need to be co-concurrently
repaired by tissue remodeling methods.
PMID- 29959435
TI - Root order-based traits of Manchurian walnut & larch and their plasticity under
interspecific competition.
AB - Manchurian walnut and larch are key timber species of northeast China but
information on (fine) root traits of both species is scarce. Plasticity of root
traits in mixed plantations has been studied rarely although this could give
important insights into mechanisms of root competition. This study examined root
traits by branching order in 30-yr-old monocultures and their plasticity in mixed
plantations. In monocultures, Manchurian walnut and larch differed in key fine
root traits. Larch roots hold more absorptive root orders, larger diameter and
lower specific root length/area. Walnut root orders featured greater cortex:stele
ratios, N-concentrations and respiration rates. Under interspecific competition,
the proportion of walnut root tips increased, the biomass/length of larch root
orders 1-3 decreased. Larch possessed a greater morphological and anatomical
plasticity of terminal root orders than walnut. Mycorrhizal colonization rates of
walnut were reduced. Both species differed fundamentally in their fine root
properties. Absorptive fine root orders reacted plastic under interspecific
competition while traits of higher root orders remained unchanged. In mixture,
larch roots possessed a greater plasticity in traits related to resource uptake
(efficiency) than walnut roots whose reaction norm is suggested to be
predominantly based on interference competition via juglone exudation.
PMID- 29959436
TI - Allogeneic hematopoietic stem cell transplantation for children and adolescents
with high-risk cytogenetic AML: distinctly poor outcomes of FUS-ERG-positive
cases.
AB - Allocating patients with acute myeloid leukemia and high-risk cytogenetic
abnormalities (HR-AML) for allogeneic hematopoietic stem cell transplantation
(allo-HSCT) is part of the standard treatment protocol; however, whether allo
HSCT truly improves the outcomes in these patients is debatable. Data on 169
children and adolescents with HR-AML who received their first allo-HSCT in first
or second remission between 2000 and 2015 were extracted from a nationwide,
Japanese HSCT registry. The 3-year disease-free survival (DFS) and overall
survival (OS) rates were 55.2% (95% CI, 46.8-62.9%) and 69.6% (61.4-76.3%),
respectively, for all the HR-AML patients. In univariate analysis, the
cytogenetic subgroup had a significant impact on both the DFS (P = 0.011) and OS
(P < 0.001) rates. In particular, 14 patients with t(16;21) showed an extremely
poor outcome. Additionally, older age at allo-HSCT (10-19 years old, P = 0.025),
myeloablative conditioning with total-body irradiation (P = 0.019), and grade II
IV acute graft-versus-host disease (GVHD, P = 0.049) were associated with
inferior OS. The donor type and occurrence of chronic GVHD did not affect the
outcome. Multivariate analysis revealed t(16;21) to be associated with increased
overall mortality (hazard ratio = 4.416, P < 0.001). Because the outcome of
patients with certain HR-AML subgroups, such as t(16;21)-positive cases, is
extremely poor even with allo-HSCT in remission, a novel therapy is urgently
required.
PMID- 29959437
TI - A prospective study of allogeneic transplantation from unrelated donors for
chronic granulomatous disease with target busulfan-based reduced-intensity
conditioning.
PMID- 29959438
TI - Surface reconstruction in gold nanowires.
AB - Surface reconstructions are caused by structural stabilization resulting from the
modulation of surface atomic positions. Studies on surface reconstruction have
been conducted for substantially large surfaces, rather than at the size of
reconstructed surface unit cells. Hence, well-known surface reconstruction
manners may not be applicable for the surfaces of nanometer-sized isolated
crystals, such as nanoclusters, nanowires and nanotubes. This is because they
have high surface area-to-interior volume ratios exceeding several tens of
percent, and their surface structures significantly affect the stabilization of
their entire structures. In this study, we demonstrate the inherent surface
reconstruction of gold nanowires via nanosecond-pulsed electromigration with the
application of tensile stresses. The results lead to evolutions in basic studies
relating to surface reconstruction and nanostructures and in applications of
nanowires, for which stabilization is essential when they are used in extremely
miniaturized integrated circuits for next-generation electronics.
PMID- 29959440
TI - How uncertainty sensitizes dopamine neurons and invigorates amphetamine-related
behaviors.
PMID- 29959439
TI - Diazepam reverses increased anxiety-like behavior, social behavior deficit, and
dopamine dysregulation following withdrawal from acute amphetamine.
AB - Psychostimulants such as amphetamine (AMPH) increase dopamine (DA) release from
ventral tegmental area (VTA) neurons, which is associated with their acute
reinforcing actions. This positive state is followed by a negative affective
state during the withdrawal period each time the drug is taken (i.e., opponent
process theory). AMPH withdrawal is accompanied by symptoms of anxiety and
depression, which are associated with DA system dysfunction in humans and animal
models. Most studies have focused on the negative affective state after
withdrawal from chronic drug administration; yet, this negative state appears
even after a drug is taken for the first time in both humans and rodents. In
rats, withdrawal from a single dose of AMPH (2 mg/kg) increases forced swim test
immobility and decreases the number of spontaneously active VTA DA neurons up to
48 h post-withdrawal. In the current study, acute AMPH withdrawal was found to
increase anxiety-like behavior in the elevated plus maze (EPM), reduce social
cage time in the three-chambered social approach test (SAT), and attenuate VTA
population activity. The effects of diazepam, a drug commonly used to treat
anxiety disorders, were tested on anxiety-like and social behavior as well as VTA
DA neuron activity following acute AMPH withdrawal. A single (5 mg/kg) dose of
diazepam circumvented the neurobehavioral effects induced by acute AMPH
withdrawal, as demonstrated by increased open arm time and social cage time as
well as normalized VTA DA activity comparable to controls, suggesting that these
neurobehavioral effects of acute AMPH withdrawal reflect an anxiety-like state.
PMID- 29959442
TI - Author Correction: T-bet-dependent NKp46+ innate lymphoid cells regulate the
onset of TH17-induced neuroinflammation.
AB - In the version of this article initially published, in second paragraph of the
second subsection of Results ('Peripheral licensing of CD4+ TH17 cells in Tbx21-/
hosts'), the figure citation ('Fig. 1c') in the sentence that begins "In
addition to" was incorrect. The correct citation is 'Fig. 1d'.
PMID- 29959441
TI - Exposure of Methicillin-Resistant Staphylococcus aureus to Low Levels of the
Antibacterial THAM-3PhiG Generates a Small Colony Drug-Resistant Phenotype.
AB - This study investigated resistance against trishexylaminomelamine
trisphenylguanide (THAM-3PhiG), a novel antibacterial compound with selective
microbicidal activity against Staphylococcus aureus. Resistance development was
examined by culturing methicillin resistant S. aureus (MRSA) with sub-lethal
doses of THAM-3PhiG. This quickly resulted in the formation of normal (WT) and
small colonies (SC) of S. aureus exhibiting minimal inhibitory concentrations
(MICs) 2* and 4* greater than the original MIC. Continuous cell passaging with
increasing concentrations of THAM-3PhiG resulted in an exclusively SC phenotype
with MIC >64 mg/L. Nuclear magnetic resonance (NMR)-based metabolomics and
multivariate statistical analysis revealed three distinct metabolic profiles for
THAM-3PhiG treated WT, untreated WT, and SC (both treated and untreated). The
metabolome patterns of the SC sample groups match those reported for other small
colony variants (SCV) of S. aureus. Supplementation of the SCV with menadione
resulted in almost complete recovery of growth rate. This auxotrophism was
corroborated by NMR analysis revealing the absence of menaquinone production in
the SCV. In conclusion, MRSA rapidly acquires resistance to THAM-3PhiG through
selection of a slow-growing menaquinone auxotroph. This study highlights the
importance of evaluating and monitoring resistance to novel antibacterials during
development.
PMID- 29959443
TI - Effect of a Multifaceted Quality Improvement Intervention on Hospital Personnel
Adherence to Performance Measures in Patients With Acute Ischemic Stroke in
China: A Randomized Clinical Trial.
AB - Importance: In China and other parts of the world, hospital personnel adherence
to evidence-based stroke care is limited. Objective: To determine whether a
multifaceted quality improvement intervention can improve hospital personnel
adherence to evidence-based performance measures in patients with acute ischemic
stroke (AIS) in China. Design, Setting, and Participants: A multicenter, cluster
randomized clinical trial among 40 public hospitals in China that enrolled 4800
patients hospitalized with AIS from August 10, 2014, through June 20, 2015, with
12-month follow-up through July 30, 2016. Interventions: Twenty hospitals
received a multifaceted quality improvement intervention (intervention group;
2400 patients), including a clinical pathway, care protocols, quality coordinator
oversight, and performance measure monitoring and feedback. Twenty hospitals
participated in the stroke registry with usual care (control group; 2400
patients). Main Outcomes and Measures: The primary outcome was hospital personnel
adherence to 9 AIS performance measures, with co-primary outcomes of a composite
of percentage of performance measures adhered to, and as all-or-none. Secondary
outcomes included in-hospital mortality and long-term outcomes (a new vascular
event, disability [modified Rankin Scale score, 3-5], and all-cause mortality) at
3, 6, and 12 months. Results: Among 4800 patients with AIS enrolled from 40
hospitals and randomized (mean age, 65 years; women, 1757 [36.6%]), 3980 patients
(82.9%) completed the 12-month follow-up of the trial. Patients in intervention
group were more likely to receive performance measures than those in the control
groups (composite measure, 88.2% vs 84.8%, respectively; absolute difference,
3.54% [95% CI, 0.68% to 6.40%], P = .02). The all-or-none measure did not
significantly differ between the intervention and control groups (53.8% vs 47.8%,
respectively; absolute difference, 6.69% [95% CI, -0.41% to 13.79%], P = .06).
New clinical vascular events were significantly reduced in the intervention group
compared with the control group at 3 months (3.9% vs 5.3%, respectively;
difference, -2.03% [95% CI, -3.51% to -0.55%]; P = .007), 6 months (6.3% vs 7.8%,
respectively; difference, -2.18% [95% CI, -4.0% to -0.35%]; P = .02) and 12
months (9.1% vs 11.8%, respectively; difference, -3.13% [95% CI, -5.28% to
0.97%]; P = .005). Conclusions and Relevance: Among 40 hospitals in China, a
multifaceted quality improvement intervention compared with usual care resulted
in a statistically significant but small improvement in hospital personnel
adherence to evidence-based performance measures in patients with acute ischemic
stroke when assessed as a composite measure, but not as an all-or-none measure.
Further research is needed to understand the generalizability of these findings.
Trial Registration: ClinicalTrials.gov Identifier: NCT02212912.
PMID- 29959444
TI - Bridging the Evidence-to-Practice Gap in Stroke Care.
PMID- 29959445
TI - Lipid Membranes and Reactions at Lipid Interfaces: Theory, Experiments, and
Applications.
PMID- 29959446
TI - [Morbidity and mortality conferences : Structure and clinical experiences].
AB - Morbidity and mortality conferences (M & M) have become increasingly more
important in Germany in recent years as an important risk management tool;
however, in addition to risk identification M & M should also promote individual
and organizational learning, a modern error culture and the optimization of
treatment processes in terms of patient safety. In order to successfully
implement this format in times of limited personnel and time resources, a
structured approach is required. Equally essential is the integration into a
clinic-wide overall concept with central structures. This article provides
recommendations for the structured implementation of M & M conferences based on
experience in a large university hospital.
PMID- 29959447
TI - Positive FABER distance test is associated with higher alpha angle in symptomatic
patients.
AB - PURPOSE: The purpose of this study was to determine the diagnostic value of the
flexion abduction external rotation (FABER) distance test (FDT) for the diagnosis
of cam-type femoroacetabular impingement (FAI) as defined by alpha angle.
METHODS: For this study, 603 patients with symptomatic, unilateral
femoroacetabular impingement were included. Patients with symptoms of hip
instability, bilateral symptoms, bilateral surgery, or bilateral alpha angles
over 55 were excluded from the analysis. A positive FDT was defined as a
difference of 4 cm or more between hips. A pathological cam was defined as an
alpha angle of 78 degrees or greater. RESULTS: The average age was 36.4 +/- 12
years, with 344 males and 259 females. Faber distance of the injured hip was
correlated with age at surgery (rho = 0.148; p < 0.001). Alpha angle on the
injured hip was positively correlated with injured hip FABER distance (rho =
0.276; p < 0.001). The average alpha angle in patients with a positive FABER
distance test was 74 degrees (SD = 11 degrees ) compared to 68 degrees (SD = 8
degrees ) in patients with a negative distance test (p = 0.001). The sensitivity
of the FDT to diagnose pathological cam was 0.848 (0.79-0.89) with a negative
predictive value of 86% (81-90%). CONCLUSION: This study demonstrated that the
FABER distance test is correlated with the alpha angle and is a good diagnostic
exam for pathological cam-type FAI as defined by and alpha angle equal to or
greater than 78 degrees . CLINICAL RELEVANCE: FABER distance test is a simple
test that can be used as a screening test to decide if FAI should be suspected
and further testing is needed. LEVEL OF EVIDENCE: III.
PMID- 29959448
TI - Cross-education improves quadriceps strength recovery after ACL reconstruction: a
randomized controlled trial.
AB - PURPOSE: The aim of this study was to investigate the effects of concentric and
eccentric cross-education (CE) on quadriceps strength and knee function
recoveries after anterior cruciate ligament (ACL) reconstruction. METHODS: Forty
eight patients (age: 29.5 +/- 6.8 years, body mass index: 26.1 +/- 3.2 kg/m2) who
had undergone ACL reconstruction with hamstring tendon autograft were included in
the study. The patients were randomly divided into three groups when they reached
four weeks post surgery: (1) concentric CE (n = 16); (2) eccentric CE (n = 16);
and (3) control (n = 16). All groups followed the same post-surgical
rehabilitation program for their reconstructed limb. Additionally, the two
experimental groups followed eight weeks of isokinetic training for the uninjured
knee at 60 degrees /s for 3 days per week. Quadriceps maximum voluntary isometric
strength (MVIC) was measured during the 4th week (pre-training), 12th week (post
training), and 24th week post surgery. The single-leg hop distance and
International Knee Documentary Committee (IKDC) scores were also evaluated during
the 24th week post surgery. Analysis of variance was used for statistical
analysis. RESULTS: Group-by-time interaction was significant for quadriceps MVICs
for reconstructed and healthy limbs (p = 0.02). Quadriceps strength of both knees
was greater in concentric and eccentric CE groups compared to control group
during the 12th- and 24th weeks post surgery (p < 0.05). Strength gain was 28%
and 31% in concentric and eccentric CE groups, respectively, when compared with
the control group. Concentric and eccentric CE had similar effects on quadriceps
strength recovery (n.s.). IKDC score, and single-leg hop distances were not
significantly different among groups (n.s.). CONCLUSIONS: Concentric and
eccentric quadricep strengthening of healthy limbs in early phases of ACL
rehabilitation improved post-surgical quadriceps strength recovery of the
reconstructed limb. CE should be integrated into ACL reconstruction
rehabilitation, especially in the early rehabilitative phases to restore
quadriceps strength. LEVEL OF EVIDENCE: Randomized controlled trial, Level I.
PMID- 29959449
TI - [Organ injuries due to thoracic trauma : Diagnostics, clinical importance and
treatment principles].
AB - Thoracic trauma can be a life-threatening condition due to the involvement of
vital organs, such as the heart, lungs, tracheobronchial tree and the great
vessels. A coordinated interdisciplinary management is vital for the survival of
the injured person. Modern diagnostic procedures provide an essential basis for
the surgical treatment of patients. Surgical treatment principles include
insertion of chest drainage, emergency thoracotomy, complex bronchoplastic and
vascular reconstructive techniques and cardiac surgical maneuvers. For this
reason highly complex surgical procedures are available, which can be effectively
and specifically integrated into an interdisciplinary concept. In this review,
the most frequent and prognostically relevant conditions, the indicated
diagnostics and their significance as well as the surgical treatment principles,
are comprehensively presented under consideration of the clinical situation.
PMID- 29959450
TI - [Fractures of the lateral process of the talus-snowboarder's ankle].
AB - Fractures of the lateral tubercle of the talus (PLT) are rare. With the
increasing popularity of the trend sport snowboarding, the incidence of PLT
fractures has increased. The most common classification of PLT fractures is the
Hawkins classification. The aim of this review was to raise awareness for the
injury and discuss the current evidence. A literature search revealed eight
studies, each including at least seven patients. Six out of the eight studies
were descriptive, retrospective case series without predefined treatment
concepts. These resulted in only moderate treatment outcomes. Due to the low
number of patients, the lack of computed tomography (CT) or magnetic resonance
imaging (MRI) and inconsistent treatment approaches, these studies do not allow
to draw conclusions on a treatment concept for PLT fractures. The other two
studies validated existing treatment regimens. Overall, surgical treatment of
dislocated fractures and conservative treatment of non-dislocated fractures was
carried out with satisfactory results. The outcome of conservative treatment of
dislocated factures remains unclear. A reason for the inconsistent treatment
results could be the observed concomitant injuries, including dislocation of the
tendons of the peroneus muscles (46%), calcaneal chondral injuries (48%) and
subluxation of the subtalar joint (7%). Based on the limited evidence available,
the authors recommend the application of CT and MRI for PLT fractures to assess
concomitant injuries, which are the primary indication for surgery. Dislocated
type I and II fractures (>2 mm) should be treated operatively, type III and non
dislocated type I and II fractures can be treated conservatively by
immobilization and partial weight-bearing for 6 weeks.
PMID- 29959451
TI - Which mental disorders are associated with the greatest impairment in
functioning?
AB - OBJECTIVE: The objective of this study is to estimate the comparative
associations of mental disorders with three measures of functional impairment:
the Global Assessment of Functioning (GAF); the number of days in the past 12
months of total inability to work or carry out normal activities because of
emotions, nerves, or mental health (i.e., days out of role); and a modified
version of the World Health Organization Disability Assessment Schedule 2.0
(WHODAS 2.0). METHODS: Secondary data analysis of the linked Mental Health
Surveillance Study and the National Survey on Drug Use and Health (n = 5653),
nationally representative population surveys conducted in the United States.
Generalized linear models assessed the independent effects of mental disorders on
each measure of functional impairment, controlling for mental disorder
comorbidity, physical health disorders, and sociodemographic factors. RESULTS:
The results varied across measures of functional impairment. However, mood
disorders generally tended to be associated with the greatest functional
impairment, anxiety disorders with intermediate impairment, and substance use
disorders with the least impairment. All 15 disorders were significantly
associated with the GAF score in multiple regression models, eight disorders were
significantly associated with the WHODAS score, and three disorders were
significantly associated with days out of role. CONCLUSIONS: Our results
highlight the value of complementary measures of functional impairment.
PMID- 29959452
TI - Attention orienting near the hand following performed and imagined actions.
AB - Recent studies have documented that the hand's ability to perform actions affects
the visual processing and attention for objects near the hand, suggesting that
actions may have specific effects on visual orienting. However, most research on
the relation between spatial attention and action focuses on actions as responses
to visual attention manipulations. The current study examines visual attention
immediately following an executed or imagined action. A modified spatial cuing
paradigm tested whether a brief, lateralized hand-pinch performed by a visually
hidden hand near the target location, facilitated or inhibited subsequent visual
target detection. Conditions in which hand-pinches were fully executed (action)
were compared to ones with no hand-pinch (inaction) in Experiment 1 and imagined
pinches (imagine) in Experiment 2. Results from Experiment 1 indicated that
performed hand pinches facilitated rather than inhibited subsequent detection
responses to targets appearing near the pinch, but target detection was not
affected by inaction. In Experiment 2, both action and imagined action conditions
cued attention and facilitated responses, but along differing time courses. These
results highlight the ongoing nature of visual attention and demonstrate how it
is deployed to locations even following actions.
PMID- 29959453
TI - Concordance of longitudinal strain and MRI in a case of myocardial contusion in a
patient with normal conventional 2D echocardiography.
PMID- 29959454
TI - Driving pressure in obese ventilated patients: another brick in the (chest) wall.
PMID- 29959456
TI - Low morphometric complexity of emphysematous lesions predicts survival in chronic
obstructive pulmonary disease patients.
AB - OBJECTIVES: To investigate whether morphometric complexity in the lung can
predict survival and act as a new prognostic marker in patients with chronic
obstructive pulmonary disease (COPD). METHODS: COPD (n = 302) patients were
retrospectively reviewed. All patients underwent volumetric computed tomography
and pulmonary function tests at enrollment (2005-2015). For complexity analysis,
we applied power law exponent of the emphysema size distribution (Dsize) as well
as box-counting fractal dimension (Dbox3D) analysis. Patients' survival at
February 2017 was ascertained. Univariate and multivariate Cox proportional
hazards analyses were performed, and prediction performances of various
combinatorial models were compared. RESULTS: Patients were 66 +/- 6 years old,
had 41 +/- 28 pack-years' smoking history and variable GOLD stages (n = 20, 153,
108 and 21 in stages I-IV). The median follow-up time was 6.1 years (range: 0.2
11.6 years). Sixty-three patients (20.9%) died, of whom 35 died of lung-related
causes. In univariate Cox analysis, lower Dsize and Dbox3D were significantly
associated with both all-cause and lung-related mortality (both p < 0.001). In
multivariate analysis, the backward elimination method demonstrated that Dbox3D,
along with age and the BODE index, was an independent predictor of survival (p =
0.014; HR, 2.08; 95% CI, 1.16-3.71). The contributions of Dsize and Dbox3D to the
combinatorial survival model were comparable with those of the emphysema index
and lung-diffusing capacity. CONCLUSIONS: Low morphometric complexity in the lung
is a predictor of survival in patients with COPD. KEY POINTS: * A newly suggested
method for quantifying lung morphometric complexity is feasible. * Morphometric
complexity measured on chest CT images predicts COPD patients' survival. *
Complexity, diffusing capacity and emphysema index contribute similarly to the
survival model.
PMID- 29959457
TI - Characterization of genes specific to sua-CMS in Nicotiana tabacum.
AB - KEY MESSAGE: Six unique ORFs were characterized in tobacco plants with sua-CMS
sterile cytoplasm, identifying the mtDNA basis for pollen sterility. sua-CMS
(cytoplasmic male sterility), the most widely used sterile system in tobacco
hybrids, is the only CMS type identified as having no negative effects on
agronomic or quality traits in tobacco (Nicotiana tabacum) and as being fully
male sterile. CMS is often associated with alterations of mitochondrial DNA
(mtDNA), including novel chimeric open reading frames (ORFs), which result from
rearrangement and recombination. Here, we obtained 34 mitochondrial ORFs in the
sua-CMS line msZhongyan100 (sZY) by BLAST analysis. When we amplified these
mitochondrial ORFs in seven tobacco CMS lines including sua-, glu-, rep-, rus-,
tab1-, tab2-, and tab3-CMS types and in fertile tobacco, we found that six ORFs
orf82, orf103, orf115a, orf91, orf115b, and orf100-were located in three small
regions (m-sr) of the mitochondrial genome of sZY and were unique to the sua-CMS
line. We further amplified the m-sr fragments in three different backcross
populations of the seven types of CMS, three F1 hybrids with sua-CMS sterile
cytoplasm, two sua-CMS lines, and 284 fertile tobacco accessions. The ORFs were
specific to plants with the sua-CMS background. All six unique ORFs were chimeric
and had no homology with the mitochondrial genomes of fertile tobacco. Transcript
analysis revealed that the ORFs were highly expressed in the anthers and floral
buds of sZY. These six ORFs were specific to sua-CMS and could be used as
molecular markers to identify sua-CMS lines, which is useful for improving
breeding for heterosis in tobacco.
PMID- 29959455
TI - Circulating biomarkers may be unable to detect infection at the early phase of
sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study.
AB - PURPOSE: Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are
the same syndromes, differing by their cause, sepsis being secondary to microbial
infection. Microbiological tests are not enough to detect infection early. While
more than 50 biomarkers have been proposed to detect infection, none have been
repeatedly validated. AIM: To assess the accuracy of circulating biomarkers to
discriminate between sepsis and non-septic SIRS. METHODS: The CAPTAIN study was a
prospective observational multicenter cohort of 279 ICU patients with hypo- or
hyperthermia and criteria of SIRS, included at the time the attending physician
considered antimicrobial therapy. Investigators collected blood at inclusion to
measure 29 plasma compounds and ten whole blood RNAs, and-for those patients
included within working hours-14 leukocyte surface markers. Patients were
classified as having sepsis or non-septic SIRS blindly to the biomarkers results.
We used the LASSO method as the technique of multivariate analysis, because of
the large number of biomarkers. RESULTS: During the study period, 363 patients
with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were
classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers
had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95%
confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as
being repeatedly associated with sepsis, and no model performed better than CRP
alone (ROC-AUC 0.76 [0.68-0.84]). CONCLUSIONS: The circulating biomarkers tested
were found to discriminate poorly between sepsis and non-septic SIRS, and no
combination performed better than CRP alone.
PMID- 29959458
TI - Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint
inhibitors in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
death worldwide. Immune checkpoint blockade with anti-CTLA-4 and anti-PD-1
antibodies has shown promising results in the treatment of patients with advanced
HCC. The anti-PD-1 antibody, nivolumab, is now approved for patients who have had
progressive disease on the current standard of care. However, a subset of
patients with advanced HCC treated with immune checkpoint inhibitors failed to
respond to therapy. Here, we provide evidence of adaptive resistance to immune
checkpoint inhibitors through upregulation of indoleamine 2,3-dioxygenase (IDO)
in HCC. Anti-CTLA-4 treatment promoted an induction of IDO1 in resistant HCC
tumors but not in tumors sensitive to immune checkpoint blockade. Using both
subcutaneous and hepatic orthotopic models, we found that the addition of an IDO
inhibitor increases the efficacy of treatment in HCC resistant tumors with high
IDO induction. Furthermore, in vivo neutralizing studies demonstrated that the
IDO induction by immune checkpoint blockade was dependent on IFN-gamma. Similar
findings were observed with anti-PD-1 therapy. These results provide evidence
that IDO may play a role in adaptive resistance to immune checkpoint inhibitors
in patients with HCC. Therefore, inhibiting IDO in combination with immune
checkpoint inhibitors may add therapeutic benefit in tumors which overexpress IDO
and should be considered for clinical evaluation in HCC.
PMID- 29959460
TI - Reproductive experience alters the involvement of N-methyl-D-aspartate receptors
in fear extinction, but not fear conditioning, in female Sprague Dawley rats.
AB - Recently, evidence has emerged showing that the behavioural and hormonal features
of fear extinction are altered as a result of reproductive experience in both
rats and humans. The current set of experiments sought to determine whether
reproductive experience also alters the molecular features of fear extinction. In
adult male rats, it has been widely demonstrated that the activation of N-methyl
D-aspartate receptors (NMDAR) is essential for fear extinction. We therefore
compared the involvement of NMDAR in fear extinction between nulliparous (virgin)
and primiparous (reproductively experienced) female rats. Nulliparous and
primiparous females received systemic administrations of either MK-801 (a non
competitive NMDAR antagonist) or saline prior to extinction training. MK-801 was
found to impair extinction recall in nulliparous females, but not primiparous
females. When the same dose of MK-801 was administered prior to conditioning,
both groups of rats showed impaired recall of conditioning the following day. The
results of these experiments indicate that the extinction, but not the
acquisition of fear, may become NMDAR-independent following reproductive
experience.
PMID- 29959459
TI - Transcriptional regulation of murine natural killer cell development,
differentiation and maturation.
AB - Natural killer (NK) cells are innate cytotoxic effector cells that play important
protective roles against certain pathogens as well as against pathogen-infected
and transformed host cells. NK cells continuously arise from adult bone marrow
resident haematopoietic progenitors. Their generation can be sub-divided into
three phases. The early NK cell development phase from multipotent common
lymphoid progenitors occurs at least in part in common with that of additional
members of a family of innate lymphoid cells, for which NK cells are the founding
member. An intermediate phase of NK cell differentiation is characterized by the
acquisition of IL-15 responsiveness and lineage-defining properties such as the
transcription of genes coding for cytotoxic effector molecules. This is followed
by a late maturation phase during which NK cells lose homeostatic expansion and
increase effector capacity. These three phases are regulated by multiple stage
specific but not NK cell-specific transcription factors. This review summarizes
the NK cell developmental and maturation processes and their transcriptional
regulation with an emphasis on data derived from genetically modified mouse
models.
PMID- 29959461
TI - The role of the basolateral amygdala and infralimbic cortex in (re)learning
extinction.
AB - The basolateral amygdala complex (BLA) and infralimbic region of the prefrontal
cortex (IL) play distinct roles in the extinction of Pavlovian conditioned fear
in laboratory rodents. In the past decade, research in our laboratory has
examined the roles of these brain regions in the re-extinction of conditioned
fear: i.e., extinction of fear that is restored through re-conditioning of the
conditioned stimulus (CS) or changes in the physical and temporal context of
extinction training (i.e., extinction of renewed or spontaneously recovered
fear). This paper reviews this research. It has revealed two major findings.
First, in contrast to the acquisition of fear extinction, which usually requires
neuronal activity in the BLA but not IL, the acquisition of fear re-extinction
requires neuronal activity in the IL but can occur independently of neuronal
activity in the BLA. Second, the role of the IL in fear extinction is determined
by the training history of the CS: i.e., if the CS was novel prior to its fear
conditioning (i.e., it had not been trained), the acquisition of fear extinction
does not require the IL; if, however, the prior training of the CS included a
series of CS-alone exposures (e.g., if the CS had been pre-exposed), the
acquisition of fear extinction was facilitated by pharmacological stimulation of
the IL. Together, these results were taken to imply that a memory of CS-alone
exposures is stored in the IL, survives fear conditioning of the CS, and can be
retrieved and strengthened during extinction or re-extinction of that CS
(regardless of whether the extinction is first- or second-learned). Hence, under
these circumstances, the initial extinction of fear to the CS can be facilitated
by pharmacological stimulation of the IL, and re-extinction of fear to the CS can
occur in the absence of a functioning BLA.
PMID- 29959462
TI - Symptomatic periprocedural intracranial hemorrhage unrelated to coil embolization
in 1287 patients with intracranial aneurysms.
AB - PURPOSE: Periprocedural symptomatic intracranial hemorrhage (sICH) unrelated to
coil embolization of intracranial aneurysm has been rarely reported. The
incidence and characteristics of this complication remain unclear. This study was
designed to elucidate the incidence and characteristics of periprocedural sICH
unrelated to coiling of intracranial aneurysm, and to explore the possible
mechanisms underlying this complication. METHODS: Included in this retrospective
study were 1287 patients with 1394 aneurysms who were treated with coil
embolization (476 patients with stent assistance and 811 patients without stents)
between May 2008 and August 2017. All procedure-unrelated sICHs that occurred
within 30 days after coiling were selected. The technical details of the
procedure, clinical characteristics, and medical therapy were recorded. RESULTS:
A total of 6 patients developed periprocedural sICH unrelated to coil
embolization. All these six patients underwent stent-assisted coiling (SAC).
Therefore, there was a 1.3% (6/476) procedure-unrelated sICH rate of SAC and 0%
(0/811) in patients underwent coiling without stent during the periprocedural
period (P = 0.005, RR 0.987; 95% CI, 0.977-0.997). These phenomena occurred more
often in patients who received SAC for ruptured aneurysms vs patients underwent
this technique for unruptured aneurysms (2.0 vs 0.7%, P = 0.390, RR 2.896; 95%
CI, 0.525-15.968). All these phenomena occurred within 7 days after coiling, and
resulted in one mortality, one unfavorable outcome (mRS Score 3), and other four
favorable outcomes (mRS Scores 0-2) at 90 days after procedure. CONCLUSION: Our
findings suggest that the procedure-unrelated sICH, though less frequent, may
exist following stent-assisted coiling of intracranial aneurysm during the
periprocedural period. Extra caution may be warranted in patients who were
treated with SAC for ruptured aneurysms.
PMID- 29959463
TI - [Pruritus in elderly people-an interdisciplinary challenge].
AB - Due to demographic change, especially in Western countries with increasing life
expectancy and a continuously increasing number of elderly, chronic pruritus (CP)
is more and more observed in clinical practice. CP in elderly may present with
specific pruritic skin diseases, as chronic prurigo (nodular form) and can also
occur in unaffected, normal looking skin. CP in elderly remains a challenge.
Especially CP without any skin lesions is a major diagnostic and therapeutic
challenge. Due to the increasing prevalence of malignant diseases in elderlies,
paraneoplastic pruritus is also an important differential diagnosis. Treatment
depends on the mobility of the patient which determines if and which topical
agents can be used and if ultraviolet phototherapy can be administered. There are
a number of topical and systemic medications, which must be selected according to
existing comorbidities, possible drug interactions, and the patient's compliance
as well as possible side effects such as cognition and sedation. All this may
hamper treatment of CP in elderly.
PMID- 29959464
TI - Reactive oxygen species induce sclerotial formation in Morchella importuna.
AB - Morels are some of the most highly prized edible and medicinal mushrooms, and the
outdoor cultivation has been achieved in China in recent years. Sclerotial
formation is one of the most important phases during the morel life cycle, and
the number of sclerotia indicates the spawn quality during cultivation. However,
the sclerotial formation and differentiation mechanisms are poorly understood. In
this study, the sclerotial formation process of Morchella importuna and the
effects of reactive oxygen species on scerotial formation were studied. Scerotial
formation was defined as five distinctive phases, hypha early, hyphal growth,
sclerotial initiation, development, and maturation. The mycelia in the sclerotium
forming area were swollen, darkened, and dense with sclerotial formation, but
hydrogen peroxide accumulated in the region lacking sclerotial formation. The
expression of all six genes for superoxide dismutases tested increased with
sclerotial maturation. A difference in hydrogen peroxide concentration of 20 mM
could promote the sclerotial initiation and induce expression of sod genes. The
MAPK signaling pathway was activated, and they passed the signal from an area of
high oxidative stress to a low area to initiate sclerotial formation. An
understanding of the sclerotial formation mechanisms in M. importuna may help to
understand the life cycle and facilitate the fruiting body cultivation.
PMID- 29959466
TI - Computed-tomography image segmentation and 3D-reconstruction of the female pelvis
for the preoperative planning of sacrocolpopexy: preliminary data.
AB - BACKGROUND: Minimally-invasive sacrocolpopexy is the gold standard procedure for
advanced apical prolapse. Nonetheless, sacrocolpopexy has potential serious
complications leading many surgeons to avoid this excellent surgical procedure.
To overcome these limitations, preoperative planning with 3D models of the female
pelvis is proposed. The aim of the study is to evaluate the feasibility of pelvic
anatomy reconstruction with the ITK-SNAP software and highlight its potential
benefits in this intervention. METHODS: Thirty patient-specific 3D models of the
female pelvis were created using ITK-SNAP and the EndoCAS Segmentation Pipeline
extension for image segmentation: contrast-enhanced computed tomography (CE-CT)
data sets of women who underwent examinations for reasons other than prolapse
were used. The distances of pelvic structures from the sacral promontory were
standardised and measured, and correlations among these distances were evaluated
with Spearman's correlation coefficient. RESULTS: Pelvic anatomy reconstruction
was feasible for all CE-CT data sets. A statistically significant correlation was
found between the distances of the cava bifurcation and common iliac vessels from
the sacral promontory. An area for proximal mesh attachment was defined: it is
free from the passage of iliac vessels in 97.5% of cases. A significant
statistical correlation was found between the distances of the midpoint of the
bispinous diameter and the uterine cervix from the sacral promontory; a process
of linear regression showed that the latter measure can be estimated by
multiplying the first one by 0.86. CONCLUSIONS: Pre-surgical 3D reconstructions
of the female pelvis using ITK-SNAP could help achieve widespread use of
sacrocolpopexy: further comparative studies are needed to evaluate the outcomes
with and without their use.
PMID- 29959465
TI - Physiology and methane productivity of Methanobacterium thermaggregans.
AB - Accumulation of carbon dioxide (CO2), associated with global temperature rise,
and drastically decreasing fossil fuels necessitate the development of improved
renewable and sustainable energy production processes. A possible route for CO2
recycling is to employ autotrophic and hydrogenotrophic methanogens for CO2-based
biological methane (CH4) production (CO2-BMP). In this study, the physiology and
productivity of Methanobacterium thermaggregans was investigated in fed-batch
cultivation mode. It is shown that M. thermaggregans can be reproducibly adapted
to high agitation speeds for an improved CH4 productivity. Moreover, inoculum
size, sulfide feeding, pH, and temperature were optimized. Optimization of growth
and CH4 productivity revealed that M. thermaggregans is a slightly alkaliphilic
and thermophilic methanogen. Hitherto, it was only possible to grow seven
autotrophic, hydrogenotrophic methanogenic strains in fed-batch cultivation mode.
Here, we show that after a series of optimization and growth improvement attempts
another methanogen, M. thermaggregas could be adapted to be grown in fed-batch
cultivation mode to cell densities of up to 1.56 g L-1. Moreover, the CH4
evolution rate (MER) of M. thermaggregans was compared to Methanothermobacter
marburgensis, the CO2-BMP model organism. Under optimized cultivation conditions,
a maximum MER of 96.1 +/- 10.9 mmol L-1 h-1 was obtained with M. thermaggregans
97% of the maximum MER that was obtained utilizing M. marburgensis in a reference
experiment. Therefore, M. thermaggregans can be regarded as a CH4 cell factory
highly suited to be applicable for CO2-BMP.
PMID- 29959467
TI - Copper deficiency anemia: review article.
AB - Copper is a crucial micronutrient needed by animals and humans for proper organ
function and metabolic processes such as hemoglobin synthesis, as a
neurotransmitter, for iron oxidation, cellular respiration, and antioxidant
defense peptide amidation, and in the formation of pigments and connective
tissue. Multiple factors, either hereditary or acquired, contribute to the
increase in copper deficiency seen clinically over the past decades. The uptake
of dietary copper into intestinal cells is via the Ctr1 transporter, located at
the apical membrane aspect of intestinal cells and in most tissues. Copper is
excreted from enterocytes into the blood via the Cu-ATPase, ATP7A, by trafficking
the transporter towards the basolateral membrane. Zinc is another important
micronutrient in animals and humans. Although zinc absorption may occur by direct
interaction with the Ctr1 transporter, its absorption is slightly different.
Copper deficiency affects physiologic systems such as bone marrow hematopoiesis,
optic nerve function, and the nervous system in general. Detailed pathophysiology
and its related diseases are explained in this manuscript. Diagnosis is made by
measuring serum copper, serum ceruloplasmin, and 24-h urine copper levels. Copper
deficiency anemia is treated with oral or intravenous copper replacement in the
form of copper gluconate, copper sulfate, or copper chloride. Hematological
manifestations are fully reversible with copper supplementation over a 4- to 12
week period. However, neurological manifestations are only partially reversible
with copper supplementation.
PMID- 29959468
TI - Perirenal capsule and scrotal involvement in immunoglobulin G4-related kidney
disease: case-based review.
AB - Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated-,
systemic disease that is characterized by IgG4 plasma cell infiltration with
fibrotic changes in various organs. The most affected organs are pancreas and
salivary glands. Kidney can be rarely involved, and is usually represented as a
renal mass and organomegaly. Usually, elevated levels of serum IgG4 more than 135
mg/dl with organ-specific features and biopsy results showing enriched
infiltration of IgG4-positive plasma cells are needed to diagnose the disease.
However, we experienced two unusual cases of IgG4-RD involving kidney. IgG4
related kidney disease (IgG4-RKD) was first reported as an extra pancreatic
feature of autoimmune pancreatitis(AIP) in 2004. Herein, we describe two cases of
such unique presentation of IgG4RKD and a literature review focusing on
clinicopathologic features of IgG4RKD. Our cases are distinct in the fact that
IgG4RD invades unusual organs such as perinephric capsule or scrotum. We reported
the patient who showed extinct perirenal capsule invasion with multi-organ
involvement including exocrine glands in comparison to previous IgG4RKD that
often involved in renal parenchyma and renal pelvis lesions. And the other
patient had scrotal invasion with multifocal renal parenchymes. Referring to the
features observed in these two cases, we could propose that as every organ can be
related to IgG4RD, we propose clinicians to confirm the disease using imaging,
serologic, and pathologic studies. We also reviewed previous reports of IgG4-RKD
and summarized diverse imaging findings and pathologic features.
PMID- 29959469
TI - The beliefs of rheumatoid arthritis patients in their subcutaneous biological
drug: strengths and areas of concern.
AB - Patients' beliefs about their prescribed medication are an important factor
influencing intentional non-adherence. This study describes rheumatoid arthritis
(RA) patients' beliefs about their subcutaneous (SC) biological medication
through the Beliefs about Medicines Questionnaire (BMQ), and potential
associations. As part of the ARCO study (Study on Adherence of Rheumatoid
arthritis patients to subCutaneous and Oral drugs), patients completed the BMQ
specifically for their SC biological medication, encompassing a necessity and a
concerns scale. The medication possession ratio (MPR) was calculated to assess
adherence to the SC biological medication. The BMQ was completed by 321 patients.
Between 71.0 and 89.7% of patients agreed/strongly agreed with necessity scale
statements, and only 7.2% had low necessity scores. Between 20.0 and 49.8% of
patients agreed/strongly agreed with four of five concern scale statements, and
72.3% agreed/strongly agreed with the concern statement regarding long-term
medication effects. The percentage with high concerns was 58.9%, and was higher
in patients not satisfied with, or with less fulfillment of, tolerability
expectations. Non-adherence percentages were, respectively, 13.8 and 13.0% (p =
0.919) in those with high or low necessity, and 16.0 and 10.6% (p = 0.171) in
those with high or low concerns. Most patients were categorized as 'ambivalent'
(58.5%; high necessity/high concerns) or 'accepting' (36.1%; high necessity/low
concerns) of their SC biological medication. The BMQ identified patients'
concerns with their SC biological medication. Because patients' concerns could
influence non-adherence to medication and future outcomes, physicians should
address this issue in the clinic by informing patients and setting clear
expectations.
PMID- 29959470
TI - Unlocking historical phenotypic data from an ex situ collection to enhance the
informed utilization of genetic resources of barley (Hordeum sp.).
AB - Key message Historical data generated during seed regeneration are valuable to
populate a bio-digital resource center for barley (Hordeum sp.). Precise
estimates of trait performance of genetic resources are considered as an
intellectually challenging, complex, costly and time-consuming step needed to
exploit the phenotypic and genetic diversity maintained in genebanks for breeding
and research. Using barley (Hordeum sp.) as a model, we examine strategies to tap
into historical data available from regeneration trials. This is a first step
toward extending the Federal ex situ Genebank into a bio-digital resource center
facilitating an informed choice of barley accessions for research and breeding.
Our study is based on historical data of seven decades collected for flowering
time, plant height, and thousand grain weight during the regeneration of 12,872
spring and winter barley accessions. Linear mixed models were implemented in
conjunction with routines for assessment of data quality. A resampling study
highlights the potential risk of biased estimates in second-order statistics when
grouping accessions for regeneration according to the year of collection or
geographic origin. Based on rigorous quality assessment, we obtained high
heritability estimates for the traits under consideration exceeding 0.8. Thus,
the best linear unbiased estimations for the three traits are a valuable source
to populate a bio-digital resource center for the IPK barley collection. The
proposed strategy to leverage historical data from regeneration trials is not
crop specific and can be used as a blueprint for other ex situ collections.
PMID- 29959471
TI - Phenotypic and genetic analysis of spike and kernel characteristics in wheat
reveals long-term genetic trends of grain yield components.
AB - KEY MESSAGE: Phenotypic and genetic analysis of six spike and kernel
characteristics in wheat revealed geographic patterns as well as long-term trends
arising from breeding progress, particularly in regard to spikelet fertility,
i.e. the number of kernels per spikelet, a grain yield component that appears to
underlie the increase in the number of kernels per spike. Wheat is a staple crop
of global relevance that faces continuous demands for improved grain yield. In
this study, we evaluated a panel of 407 winter wheat cultivars for six
characteristics of spike and kernel development. All traits showed a large
genotypic variation and had high heritabilities. We observed geographic patterns
for some traits in addition to long-term trends showing a continuous increase in
the number of kernels per spike. This breeding progress is likely due to the
increase in spikelet fertility, i.e. the number of kernels per spikelet. While
the number of kernels per spike and spikelet fertility were significantly
positively correlated, both traits showed a significant negative correlation with
thousand-kernel weight. Genome-wide association mapping identified only small-
and moderate-effect QTL and an effect of the phenology loci Rht-D1 and Ppd-D1 on
some of the traits. The allele frequencies of some QTL matched the observed
geographic patterns. The quantitative inheritance of all traits with
contributions of additional small-effect QTL was substantiated by genomic
prediction. Taken together, our results suggest that some of the examined traits
were already the basis of grain yield progress in wheat in the past decades. A
more targeted exploitation of the available variation, potentially coupled with
genomic approaches, may assist wheat breeding in continuing to increase yield
levels globally.
PMID- 29959472
TI - Identification and characterization of Rht25, a locus on chromosome arm 6AS
affecting wheat plant height, heading time, and spike development.
AB - KEY MESSAGE: This study identified Rht25, a new plant height locus on wheat
chromosome arm 6AS, and characterized its pleiotropic effects on important
agronomic traits. Understanding genes regulating wheat plant height is important
to optimize harvest index and maximize grain yield. In modern wheat varieties
grown under high-input conditions, the gibberellin-insensitive semi-dwarfing
alleles Rht-B1b and Rht-D1b have been used extensively to confer lodging
tolerance and improve harvest index. However, negative pleiotropic effects of
these alleles (e.g., poor seedling emergence and reduced biomass) can cause yield
losses in hot and dry environments. As part of current efforts to diversify the
dwarfing alleles used in wheat breeding, we identified a quantitative trait locus
(QHt.ucw-6AS) affecting plant height in the proximal region of chromosome arm 6AS
(< 0.4 cM from the centromere). Using a large segregating population (~ 2800
gametes) and extensive progeny tests (70-93 plants per recombinant family), we
mapped QHt.ucw-6AS as a Mendelian locus to a 0.2 cM interval (144.0-148.3 Mb,
IWGSC Ref Seq v1.0) and show that it is different from Rht18. QHt.ucw-6AS is
officially designated as Rht25, with Rht25a representing the height-increasing
allele and Rht25b the dwarfing allele. The average dwarfing effect of Rht25b was
found to be approximately half of the effect observed for Rht-B1b and Rht-D1b,
and the effect is greater in the presence of the height-increasing Rht-B1a and
Rht-D1a alleles than in the presence of the dwarfing alleles. Rht25b is
gibberellin-sensitive and shows significant pleiotropic effects on coleoptile
length, heading date, spike length, spikelet number, spikelet density, and grain
weight. Rht25 represents a new alternative dwarfing locus that should be
evaluated for its potential to improve wheat yield in different environments.
PMID- 29959473
TI - Co-targeting PLK1 and mTOR induces synergistic inhibitory effects against
esophageal squamous cell carcinoma.
AB - : Both polo-like kinase 1 (PLK1) and mammalian/mechanistic target of rapamycin
(mTOR) are attractive therapeutic targets for cancer therapy. However, the
efficacy of the combined inhibition of both pathways for treating esophageal
squamous cell carcinoma (ESCC), an aggressive malignancy with poor prognosis,
remains unknown. In this study, we found that suppression of PLK1 by specific
siRNA or inhibitor attenuated mTOR activity in ESCC cells. Phosphorylated S6, a
downstream effector of mTOR signaling, was significantly correlated with
overexpression of PLK1 in a subset of ESCC. These data suggest that PLK1
activates mTOR signaling in vitro and in vivo. More importantly, the mTOR
inhibitor rapamycin synergized with PLK1 inhibitor BI 2536 to inhibit ESCC cell
proliferation in culture and in mice. Notably, combined treatment with BI 2536
and rapamycin produced more potent inhibitory effects on the activation of S6 and
AKT than either alone. Further analysis reveals that PLK1 modulates both mTOR
complex 1 (mTORC1) and mTOR complex 2 (mTORC2) cascades. Therefore, dual
inhibition of PLK1 and mTOR yields stronger antitumor effects, at least partially
due to synergistic abrogated the activation of S6, eukaryotic initiation factor
4E-binding protein 1 (4E-BP1), and AKT by cooperatively blocking mTORC1 and
mTORC2 cascades. These results provide evidence that the mTOR inhibitor rapamycin
synergistically enhances the antitumor effect of PLK1 inhibitor BI 2536 in ESCC
cells. Simultaneous targeting of PLK1 and mTOR may thus be a novel and promising
therapeutic strategy for ESCC. KEY MESSAGES: PLK1 potentiates both mTORC1 and
mTORC2 activities in ESCC cells. PLK1 expression positively correlated with mTOR
activity in a subset of ESCC. Co-targeting of PLK1 and mTOR produced stronger
antitumor effects partially due to synergistic inhibition of AKT, 4E-BP1 and S6
through cooperatively blocking mTORC2 and mTORC1 cascades. Combination targeting
of PLK1 and mTOR may be a novel and promising therapeutic strategy for ESCC
treatment.
PMID- 29959474
TI - Expression of IL-17F is associated with non-pathogenic Th17 cells.
AB - : IL-17A and IL-17F share the highest sequence homology of the IL-17 family and
signal via the same IL-17RA/RC receptor heterodimer. To better explore the
expression of these two cytokines, we used a double reporter mouse strain (IL
17DR mice), where IL-17A expressing cells are marked by enhanced green
fluorescent protein (eGFP) while red fluorescence protein (RFP) reports the
expression of IL-17F. In steady state, we found that Th17 and gammadelta T cells
only expressed IL-17A, while IL-17F expression was restricted to CD8 T cells
(Tc17) and innate lymphoid cells (ILC type 3) of the gut. In experimental
autoimmune encephalomyelitis, the vast majority of CNS-infiltrating Th17 cells
expressed IL-17A but not IL-17F. In contrast, anti-CD3-induced, TGF-beta-driven
Th17 cells in the gut expressed both of these IL-17 cytokines. In line with this,
in vitro differentiation of Th17 cells in the presence of IL-1beta led primarily
to IL-17A expressing T cells, while TGF-beta induced IL-17F co-expressing Th17
cells. Our results suggest that expression of IL-17F is associated with non
pathogenic T cells, pointing to a differential function of IL-17A versus IL-17F.
KEY MESSAGES: Naive mice: CD4+ T cells and gammadelta T cells express IL-17A, and
Tc17 cells express IL-17F. Gut ILC3 show differential expression of IL17A and F.
Th17 differentiation with TGF-beta1 induces IL-17A and F, whereas IL-1beta
induced cells expressing IL-17A. Th17 cells in EAE in CNS express IL-17A only.
Gut Th17 cells induced by anti-CD3 express IL-17A and F together as skin
gammadelta T cells of IMQ-treated mice.
PMID- 29959477
TI - [Laparoscopic colposuspension for the treatment of urinary incontinence in
women].
PMID- 29959476
TI - The Standard Genetic Code Facilitates Exploration of the Space of Functional
Nucleotide Sequences.
AB - The standard genetic code is well known to be optimized for minimizing the
phenotypic effects of single-nucleotide substitutions, a property that was likely
selected for during the emergence of a universal code. Given the fitness
advantage afforded by high standing genetic diversity in a population in a
dynamic environment, it is possible that selection to explore a large fraction of
the space of functional proteins also occurred. To determine whether selection
for such a property played a role during the emergence of the nearly universal
standard genetic code, we investigated the number of functional variants of the
Escherichia coli PhoQ protein explored at different time scales under translation
using different genetic codes. We found that the standard genetic code is highly
optimal for exploring a large fraction of the space of functional PhoQ variants
at intermediate time scales as compared to random codes. Environmental changes,
in response to which genetic diversity in a population provides a fitness
advantage, are likely to have occurred at these intermediate time scales. Our
results indicate that the ability of the standard code to explore a large
fraction of the space of functional sequence variants arises from a balance
between robustness and flexibility and is largely independent of the property of
the standard code to minimize the phenotypic effects of mutations. We propose
that selection to explore a large fraction of the functional sequence space while
minimizing the phenotypic effects of mutations contributed toward the emergence
of the standard code as the universal genetic code.
PMID- 29959475
TI - The multisystemic functions of FOXD1 in development and disease.
AB - Transcription factors (TFs) participate in a wide range of cellular processes due
to their inherent function as essential regulatory proteins. Their dysfunction
has been linked to numerous human diseases. The forkhead box (FOX) family of TFs
belongs to the "winged helix" superfamily, consisting of proteins sharing a
related winged helix-turn-helix DNA-binding motif. FOX genes have been
extensively present during vertebrates and invertebrates' evolution,
participating in numerous molecular cascades and biological functions, such as
embryonic development and organogenesis, cell cycle regulation, metabolism
control, stem cell niche maintenance, signal transduction, and many others.
FOXD1, a forkhead TF, has been related to different key biological processes such
as kidney and retina development and embryo implantation. FOXD1 dysfunction has
been linked to different pathologies, thereby constituting a diagnostic biomarker
and a promising target for future therapies. This paper aims to present, for the
first time, a comprehensive review of FOXD1's role in mouse development and human
disease. Molecular, structural, and functional aspects of FOXD1 are presented in
light of physiological and pathogenic conditions, including its role in human
disease aetiology, such as cancer and recurrent pregnancy loss. Taken together,
the information given here should enable a better understanding of FOXD1 function
for basic science researchers and clinicians.
PMID- 29959478
TI - Testing the dogma that total phospholipid fatty acid composition of blood plays a
role in kidney stone pathogenesis, using a high-low risk human model: results
from a pilot study.
AB - Previous studies have suggested that omega-3 and omega-6 polyunsaturated fatty
acid (PUFA) composition in plasma and red blood cell (RBC) total phospholipids
plays a role in urolithiasis. Our aim was to test the robustness of this dogma by
retrospectively comparing baseline profiles of these parameters in subjects from
high- and low-stone-risk groups. The documented difference in stone occurrence in
white (relatively common) (W) and black (rare) (B) subjects prompted us to select
these groups as the high-low risk model for the study. Blood and urine samples
were obtained from ten subjects in each group and were analysed for PUFAs and
stone risk factors, respectively. Concentrations of linoleic acid (LA),
eicosadienoic acid (EDA) and arachidonic acid (AA) in plasma and or/RBC total
phospholipids were significantly higher in B. Differences in other PUFA profiles
were also observed. There was no inter-group difference in AA/LA ratios. Urinary
oxalate was significantly higher while urinary phosphate was significantly lower
in B. We speculate that elevated AA in B might arise because of a possibly
enhanced elongation of LA to EDA, as well as an enhanced ?-8-desaturation of EDA
to dihomo-gamma-linolenic acid (DGLA), which is the immediate precursor of AA.
Alternatively, we speculate that the ?-5-desaturation step of DGLA to AA might be
more highly activated in this group. Irrespective of the mechanism, our observed
inter-group differences in phospholipid PUFA composition are in conflict with
previously published dogma which relates PUFA characteristics to high- and low
stone risk.
PMID- 29959479
TI - Combined antegrade and retrograde access to difficult ureters: revisiting the
rendezvous technique.
AB - INTRODUCTION: Complex ureteric strictures present a significant challenge to the
endourologist and uro-radiologist. Multiple separate interventions to try to
cross the stricture are often attempted. We describe our experience managing a
heterogenous patient group using the 'rendezvous' procedure. METHODS AND
MATERIALS: 16 patients and 18 ureters (one bilateral procedure, and two separate
procedures in one patient) underwent rendezvous procedures. Seven patients had
coexisting ureteric calculi treated. Each case was followed up for between 3
months and 5 years. RESULTS: In 16/18 ureters there was technical success at time
of surgery; successfully crossing the stricture, allowing ureteroscopic access to
the ureter, dilating and/or stenting the ureter. 2/18 were unsuccessful; one
secondary to advanced malignancy resulting in a uretero-vaginal fistula and the
second a failure to remove a retained, displaced ureteric stent. Of the 18
ureteric procedures; 7/18 were stent free at 3 months, improving to 8/18 stent
free at 6 months. 4/18 remained nephrostomy dependent (failure of drainage
despite stent or failure to stent) at 3 months, increasing to 6/18 being
nephrostomy dependent at 6 months. 1/16 remained dialysis dependent with a
nephrostomy tube. For those procedures involving ureteric calculi, 6/7 were stone
free and 1/5 had a persistent stone fragment requiring further intervention.
CONCLUSIONS: A combined approach may decrease the number of separate
interventions required, with the aim of removing the need for a long-term
nephrostomy, as well as providing opportunity to treat ureteric calculi in the
context of stricture disease. Our experience has been that where the rendezvous
has been required to treat strictures caused by malignant extrinsic compression,
stenting has not been successful; this information is key to informed consent in
a group of patients who may have a limited life expectancy.
PMID- 29959480
TI - [Histopathology of the skin-clinically relevant and innovative].
PMID- 29959481
TI - ?
PMID- 29959482
TI - Overoptimism in cross-validation when using partial least squares-discriminant
analysis for omics data: a systematic study.
AB - Advances in analytical instrumentation have provided the possibility of examining
thousands of genes, peptides, or metabolites in parallel. However, the cost and
time-consuming data acquisition process causes a generalized lack of samples.
From a data analysis perspective, omics data are characterized by high
dimensionality and small sample counts. In many scenarios, the analytical aim is
to differentiate between two different conditions or classes combining an
analytical method plus a tailored qualitative predictive model using available
examples collected in a dataset. For this purpose, partial least squares
discriminant analysis (PLS-DA) is frequently employed in omics research.
Recently, there has been growing concern about the uncritical use of this method,
since it is prone to overfitting and may aggravate problems of false discoveries.
In many applications involving a small number of subjects or samples, predictive
model performance estimation is only based on cross-validation (CV) results with
a strong preference for reporting results using leave one out (LOO). The
combination of PLS-DA for high dimensionality data and small sample conditions,
together with a weak validation methodology is a recipe for unreliable
estimations of model performance. In this work, we present a systematic study
about the impact of the dataset size, the dimensionality, and the CV technique
used on PLS-DA overoptimism when performance estimation is done in cross
validation. Firstly, by using synthetic data generated from a same probability
distribution and with assigned random binary labels, we have obtained a dataset
where the true classification rate (CR) is 50%. As expected, our results confirm
that internal validation provides overoptimistic estimations of the
classification accuracy (i.e., overfitting). We have characterized the CR
estimator in terms of bias and variance depending on the internal CV technique
used and sample to dimensionality ratio. In small sample conditions, due to the
large bias and variance of the estimator, the occurrence of extremely good CRs is
common. We have found that overfitting peaks when the sample size in the training
subset approaches the feature vector dimensionality minus one. In these
conditions, the models are neither under- or overdetermined with a unique
solution. This effect is particularly intense for LOO and peaks higher in small
sample conditions. Overoptimism is decreased beyond this point where the
abundance of noisy produces a regularization effect leading to less complex
models. In terms of overfitting, our study ranks CV methods as follows: Bootstrap
produces the most accurate estimator of the CR, followed by bootstrapped Latin
partitions, random subsampling, K-Fold, and finally, the very popular LOO
provides the worst results. Simulation results are further confirmed in real
datasets from mass spectrometry and microarrays.
PMID- 29959483
TI - Yiyang Dong (Ed.): Direct analysis in real time mass spectrometry: principles and
practices of DART-MS.
PMID- 29959484
TI - Rapid and sensitive SERS detection of the cytokine tumor necrosis factor alpha
(tnf-alpha) in a magnetic bead pull-down assay with purified and highly Raman
active gold nanoparticle clusters.
AB - Tumor necrosis factor alpha (TNF-alpha) is a cytokine with significance in early
diagnosis of cardiovascular diseases, obesity and insulin resistance. We
demonstrate the proof of concept for a rapid and sensitive detection of TNF-alpha
using a magnetic bead pull-down assay in combination with surface-enhanced Raman
scattering (SERS). The use of purified and highly SERS-active small clusters of
gold nanoparticles (AuNP) provides the high sensitivity of the assay with a limit
of detection of ca. 1 pg/mL. Continuous density gradient centrifugation was
employed for separating the very bright silica-encapsulated AuNP dimers and
trimers from the significantly weaker AuNP monomers. Negative control experiments
with other cytokines (IL-6, IL-8) and bovine serum albumin (BSA) confirm the high
specificity of the assay, but indicate also space for future improvements by
further reducing non-specific binding between proteins and the SERS nanotags. The
multiplexing potential of this SERS-based detection scheme is exemplarily
demonstrated by using a set of three spectrally distinct and highly SERS-active
AuNP clusters with unique spectral barcodes. Graphical abstract ?.
PMID- 29959485
TI - Instrumental analysis of microplastics-benefits and challenges.
AB - There is a high demand for easy, cheap, comparable, and robust methods for
microplastic (MP) analysis, due to the ever-increasing public and scientific
interest in (micro-) plastic pollution in the environment. Today, a multitude of
methodologies for sampling, sample preparation, and analysis of MPs are in use.
This feature article deals with the most prominent detection methods as well as
with sampling strategies and sample preparation techniques. Special emphasis is
on their benefits and challenges. Thus, spectroscopic methods, coupled with
microscopy, require time-consuming sample preparation and extended measurement
times, whereas thermo-analytical methods are faster but lack the ability to
determine the size distribution in samples. To that effect, most of the described
methods are applicable depending on the defined analytical question. Graphical
abstract ?.
PMID- 29959486
TI - The application of UV resonance Raman spectroscopy for the differentiation of
clinically relevant Candida species.
AB - Candida-related infections have become a major problem in hospitals. The species
identification of yeast is the prerequisite for the initiation of adequate
antifungal therapy. In the present study, the connection between inherent UV
resonance Raman (RR) spectral profiles of Candida species and taxonomic
differences was investigated for the first time. UV RR in combination with
statistical modeling was applied to extract taxonomic information from the
spectral fingerprints for subsequent differentiation. The identification
accuracies of independent batch cultures were determined by applying a leave-one
batch-out cross validation. The quality of differentiation can be divided into
three levels. Within a defined taxonomic group comprising the species C.
glabrata, C. guilliermondii, and C. haemulonii, the identification accuracy was
low. On the next level, the identification results of C. albicans and C.
tropicalis were characterized by high sensitivities of 98 and 95% but
simultaneously challenged by false-positive predictions due to the misallocation
of C. spherica (as C. albicans) and C. viswanathii (as C. tropicalis). The
highest level of identification accuracies was reached for the species C.
dubliniensis, C. krusei, C. africana, C. novergica, and C. parapsilosis. Reliable
identification results were observed with accuracies ranging from 93 up to 100%.
The species allocation based on the UV RR spectral profiles could be reproduced
by the identification of independent batch cultures. We conclude that the
introduced spectroscopic approach is capable of transforming the high-dimensional
UV RR data of Candida species into clinically useful decision parameters.
Graphical abstract.
PMID- 29959487
TI - An electrochemical biosensor for the detection of Pb2+ based on G-quadruplex DNA
and gold nanoparticles.
AB - We present a novel simple strategy for the detection of Pb2+ based on G
quadruplex DNA and gold nanoparticles. First, gold nanoparticles were chemically
adsorbed onto the surface of a thiol-modified gold electrode. Subsequently, the
substrate DNA1 was adsorbed onto the surfaces of the gold nanoparticles via thiol
gold bonds, so that the complementary guanine-rich DNA2 could be hybridized to
the gold electrode in sequence. [Ru(NH3)6]3+ (RuHex), which can be
electrostatically adsorbed onto the anionic phosphate of DNA, served as an
electrochemical probe. The presence of Pb2+ can induce DNA2 to form a stable G
quadruplex and fall off the gold electrode. The amount of RuHex remaining on the
electrode surface was determined by electrochemical chronocoulometry (CC). The
prepared biosensor showed high sensitivity for Pb2+ with a linear range with
respect to ln(cPb2+) from 0.01 to 200 nM and a low detection limit of 0.0042 nM
under optimal conditions. Because of the high selectivity of the Pb2+-specific
DNA2, the designed biosensor also showed low false-positive signal rates with
other metal ions in real-world examples. Therefore, this strategy has the
potential for practical application in environmental monitoring. Graphical
abstract ?.
PMID- 29959488
TI - Operative Stabilization of Chest Wall Trauma: Single-Center Report of Initial
Management and Long-Term Outcome.
AB - BACKGROUND: Conservative treatment of even severe thoracic trauma including flail
chest was traditionally the standard of care. Recently, we reported possible
benefits of surgical chest wall stabilization in accordance with other groups.
The aim of this study was to critically review our indications and results of
internal fixation of rib fractures in the long-term course. METHODS: We
retrospectively analyzed the data of a consecutive series of patients with
internal rib fracture fixation at our institution from 8/2009 until 12/2014, and
we retrospectively studied the late outcome through clinical examination or
personal interview. RESULTS: From 1398 patients, 235 sustained a severe thoracic
trauma (AIS >=3). In 23 of these patients, 88 internal rib fixations were
performed using the MatrixRIB(r) system. The median age of these operated
patients was 56 years [interquartile range (IQR) 49-63] with a median ISS of 21
[IQR 16-29]. From 18 local resident patients, follow-up was obtained after an
average time period of 27.6 (12-68) months. Most of these patients were free of
pain and had no limitations in their daily routine. Out of all implants, 5 splint
tips perforated the ribs in the postoperative course, but all patients remained
clinically asymptomatic. Plate osteosynthesis showed no loss of reduction in the
postoperative course. No cases of hardware prominence, wound infection or non
union occurred. CONCLUSIONS: In our carefully selected thoracic trauma patients,
locked plate rib fixation seemed to be safe and beneficial not only in the early
posttraumatic course, but also after months and years, patients remain
asymptomatic and complete recovery as a rule. Trial registration number KEK BASEC
Nr. 2016-01679.
PMID- 29959489
TI - World Journal of Surgery Becomes the Official Publication of the ERAS Society.
PMID- 29959490
TI - Robotic Reoperative Anti-reflux Surgery: Low Perioperative Morbidity and High
Symptom Resolution.
AB - BACKGROUND: Laparoscopic reoperative anti-reflux surgery (ARS) has a
significantly higher morbidity than laparoscopic primary ARS; however, it is not
known whether the same pattern exists within the robotic approach. We aimed to
evaluate the safety and efficacy of robotic reoperative ARS in comparison with
primary robotic ARS. METHODS: A retrospective review of patients undergoing
primary or reoperative robotic ARS at a tertiary referral center between 2012 and
2017 was performed. Perioperative outcomes and long-term symptom resolution were
evaluated. RESULTS: A total of 200 patients were included (38 reoperative and 162
primary ARS). Baseline characteristics were comparable across groups. Seven
(18.4%) of the reoperative patients had two or more prior foregut operations.
Patients in the reoperative group had a longer operative time (226 vs. 180 min, p
< 0.001). There were no conversions to open technique, and one patient in the
reoperative group (2.6%) had an intraoperative perforation. Twenty of the 38
reoperative patients (52.6%) were discharged within 24 h as compared to 109/162
primary patients (64.9%) (p = 0.09). The readmission rate and postoperative
complication rates were 6 and 3%, respectively, and did not differ between
groups. At a mean follow-up of 1 year, complete or partial resolution of
preoperative symptoms was achieved in 97% of primary patients and 100% of
reoperative patients (p = 0.4). CONCLUSION: The robotic approach allows for
minimal morbidity, short length of stay, and excellent functional outcomes in
patients undergoing reoperative ARS when compared to patients undergoing primary
ARS.
PMID- 29959491
TI - Impact of Micrometastatic Axillary Nodes on Survival of Breast Cancer Patients
with Tumors <=2 cm.
AB - BACKGROUND: This study investigated the impact of pN1mi disease on the survival
of T1 breast cancer patients and examined the clinical usefulness of the online
PREDICT tool and updated staging system. METHODS: The node stages of 2344
patients were divided into pN0, pN1mi, and pN1a. Clinicopathological parameters
and survival outcomes were retrospectively analyzed. Data for 111 micrometastatic
diseases were applied to the PREDICT version 2.0 and re-classified using the 8th
edition of the cancer staging manual. RESULTS: Univariable analyses demonstrated
worse disease-free and overall survival rates for patients with node-positive
cancer; however, the significance was not maintained in multivariable analyses.
Chemotherapy improved outcomes in patients with node-positive and non-luminal A
like subtype cancers. The PREDICT tool demonstrated good performance when
estimating the 5-year overall survival for pN1mi disease (area under the receiver
operating characteristic curve, 0.834). According to the updated staging system,
74% of cases were down-staged to IA, and clearly splitting survival curves were
identified. CONCLUSION: pN1mi disease alone did not adversely affect survival
outcomes. Biologic and treatment factors determined outcomes in cases of small
volume node micrometastasis. The PREDICT tool or new staging classification could
help predict the survival of patients with micrometastatic sentinel nodes.
PMID- 29959492
TI - Antibiotic Prophylaxis for Pyloromyotomy in Children: An Opportunity for Better
Stewardship.
AB - INTRODUCTION: Surgical site infection is very uncommon after pyloromyotomy in
children, and it is considered a "clean" procedure under the traditional wound
classification system. This study aims to investigate prophylactic antibiotic
administration for pyloromyotomy among children's hospitals in the USA. METHODS:
The Pediatric Health Information System (PHIS) database was retrospectively
reviewed from 2014 to 2015 including all patients less than 1 year old who had a
principal diagnosis of pyloric stenosis and underwent pyloromyotomy. Patient
demographics, hospital length of stay, and perioperative antibiotic
administration were extracted. RESULTS: A total of 4206 patients met study
criteria. Most patients were male (84%) and Caucasian (70%). The median age at
admission was 32 days (IQR 24-44 days), and median length of stay was 2 days (IQR
1-2 days). Antibiotics were administered perioperatively in 2153 (51%) patients
with marked variation among children's hospitals. Antibiotics were given to more
than 10% of patients in more than 90% of hospitals, and only two of 49 hospitals
gave no antibiotic prophylaxis. CONCLUSIONS: This study has shown that at several
tertiary-level children's hospitals in the USA, antibiotic prophylaxis is
administered for pyloromyotomy, a "clean" procedure. This highlights the need for
standardization of care and more effective antibiotic stewardship in pediatric
surgery.
PMID- 29959493
TI - Whole-Body Computed Tomography During Initial Management and Mortality Among
Adult Severe Blunt Trauma Patients: A Nationwide Cohort Study.
AB - BACKGROUND: Whole-body computed tomography (WBCT) is increasingly being
incorporated into the initial management of blunt trauma patients. Several
observational studies have suggested that, compared to selective CT, WBCT is
associated with lower mortality. In contrast, a randomized controlled trial found
no significant difference in survival between patients undergoing WBCT compared
to selective CT. Our objective was to confirm the association between WBCT and in
hospital mortality among adult severe blunt trauma patients. METHODS: This was a
retrospective cohort study based on Japan Trauma Data Bank 2004-2015 registry
data. The study population comprised adult severe blunt trauma patients with at
least one abnormal vital sign: systolic blood pressure <=100 mmHg, heart rate
>=120, respiratory rate >=30 or <=10, or Glasgow Coma Score <=13. The primary
outcome was in-hospital mortality. To adjust for both measured and unmeasured
confounders, we performed instrumental variable (IV) analysis to compare the in
hospital mortality of patients undergoing WBCT with those undergoing selective
CT. RESULTS: Of 40,435 patients who were eligible for this study, 19,766 (48.9%)
patients underwent WBCT. The proportion of patients undergoing WBCT significantly
increased during the study period, from 10.7% in 2004 to 59.6% in 2015. Primary
IV analysis showed a significant association between WBCT and lower in-hospital
mortality (odds ratio 0.84, 95% confidence interval 0.72-0.98). CONCLUSIONS: WBCT
can be beneficial in patients with blunt trauma which has compromised vital
signs. These findings from a nationwide study suggest that physicians should
consider WBCT for blunt trauma patients when warranted by vital signs.
PMID- 29959494
TI - Recurrent Falls Among Elderly Patients and the Impact of Anticoagulation Therapy.
AB - BACKGROUND: Falls are the leading source of injury and trauma-related hospital
admissions for elderly adults in the USA. Elderly patients with a history of a
fall have the highest risk of falling again, and the decision on whether to
continue anticoagulation after a fall is difficult. To inform this decision, we
evaluated the rate of recurrent falls and the impact of anticoagulation on
outcomes. METHODS: All patients of age >= 65 years and hospitalized for a fall
in the first 6 months of 2013 and 2014 were identified in the nationwide
readmission database, a nationally representative all-payer database tracking
patient readmissions. Readmissions for a recurrent fall within 6 months, and
mortality and bleeding injuries (intracranial hemorrhage, solid organ bleed, and
hemothorax) during readmission were identified. Logistic regression evaluated
factors associated with mortality on repeat falls. RESULTS: Of the 331,982
patients admitted for a fall, 15,565 (4.7%) were admitted for a recurrent fall
within 6 months. The median time to repeat fall was 57 days (IQR 19-111 days),
and 9.0% (1406) of repeat fallers were on anticoagulation. The rate of bleeding
injury was similar regardless of anticoagulation status (12.8 vs. 12.7% not on
anticoagulation, p = 0.97); however, among patients with a bleeding injury, those
on anticoagulation had significantly higher mortality (21.5 vs. 6.9% not on
anticoagulation, p < 0.01). CONCLUSION: Among patients hospitalized for a fall,
4.7% will be hospitalized for a recurrent fall within 6 months. Patients on
anticoagulation with repeat falls do not have increased rates of bleeding injury
but do have significantly higher rates of death with a bleeding injury. This
information is essential to discuss with patients when deciding to restart their
anticoagulation.
PMID- 29959495
TI - Treatment of Breast Animation Deformity in Implant-Based Reconstruction with
Selective Nerve Ablation.
AB - Breast animation deformity is a known complication of subpectoral implant
placement that is usually corrected by repositioning the implant to the
prepectoral position. Other less common treatment options include performing the
muscle splitting biplanar technique, triple plane technique, neuromodulator
injections, and secondary neurotomies via transection of the pectoral muscle. We
report a patient with animation deformity successfully treated with direct
identification and ablation of the medial and lateral pectoral nerves using
selective bipolar electrocautery. The patient is a woman with a history of
invasive ductal carcinoma who underwent bilateral mastectomy and breast
reconstruction with subpectoral implant placement and autologous fat grafting.
Within 1 year of her breast reconstruction, she developed hyperactive pectoralis
muscle contraction with resulting distortion of both breasts. Given the
disadvantages of repositioning the implant to the prepectoral position and
transecting the pectoralis muscles via secondary neurotomy, we chose to directly
identify and selectively ablate distal branches of the medial and lateral
pectoral nerves. This offers a novel technique for correcting breast animation
deformity without transecting the pectoralis muscles, causing muscle atrophy, and
preserving the subpectoral implant position.Level of Evidence V This journal
requires that authors assign a level of evidence to each article. For a full
description of these evidence-based medicine ratings, please refer to the table
of contents or the online instructions to authors www.springer.com/00266 .
PMID- 29959496
TI - A Novel Technique of Asian Tip Plasty: Rein-Shaped Columellar Strut Graft.
AB - BACKGROUND: The columellar strut graft is one of the most commonly used invisible
grafts in tip plasty techniques for nasal tip projection. However, the columellar
strut graft induces cephalic rotation of the dome with nasal tip projection. This
is an effective change in Western people with a long nose; however, this change
should be avoided in Asians who have a relatively short nose and visible
nostrils. We designed a more convenient and effective technique using a rein
shaped columellar strut graft that can prevent cephalic rotation of the dome.
METHODS: A total of 32 patients underwent surgery with a rein-shaped columellar
strut graft with a septal cartilage. The projection and location of the nasal
tip, nasal length, and nasolabial angle were measured after taking a photograph
of the lateral view, and the preoperative and postoperative results were
compared. RESULTS: There were statistically significant differences between the
preoperative and postoperative values of the nasal tip projection ratio and nasal
tip location ratio. There were no revision surgeries and no direct complications
associated with the use of the columellar strut graft. CONCLUSION: We performed
tip plasty with a modified columellar strut graft-the rein-shaped columellar
strut graft. In most cases of using this method, the tip projection was increased
and the cephalic rotation of the tip was prevented. This surgical procedure can
also be used for lengthening (rotating caudally) of the nose in some cases, as
well as for the purpose of preventing the cephalic rotation of the tip. LEVEL OF
EVIDENCE IV: This journal requires that authors assign a level of evidence to
each article. For a full description of these Evidence-Based Medicine ratings,
please refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266 .
PMID- 29959497
TI - FGF23-klotho axis, bone fractures, and arterial stiffness in dialysis: a case
control study.
AB - : We performed a case-control study on 130 age- and sex-matched hemodialysis
patients. In multivariate analysis, we observed that FGF23 levels were associated
with fracture incidence and that soluble alpha-klotho levels were associated with
the aortic-brachial arterial stiffness ratio. INTRODUCTION: New bone markers such
as sclerostin, Dickkopf-related protein 1 (DKK1), fibroblast growth factor-23
(FGF23), and alpha-klotho have been identified as potential key players in bone
and vascular abnormalities of chronic kidney disease. Therefore, we aimed to
assess whether these markers are associated with fractures, bone metabolism, and
vascular stiffness in dialysis patients. METHODS: In a prospective hemodialysis
cohort, where plasma samples and vascular assessment were performed at baseline,
we matched patients who experienced a fracture during follow-up with sex- and age
matched non-fractured patients on a 1:4 ratio. Sclerostin, DKK1, alpha-klotho,
FGF23, and markers of bone formation (alkaline phosphatase and procollagen type 1
N terminal propeptide [P1NP]) and bone resorption (tartrate-resistant acid
phosphatase 5b [TRAP5b]) were measured in baseline plasma samples. Aortic
brachial pulse wave velocity ratio, a blood pressure independent measure of
arterial stiffness, was used to assess vascular stiffness at baseline. RESULTS:
We included 130 hemodialysis patients (26 fractured, 104 non-fractured) with a
median follow-up of 42 months and a median age of 72 years. In multivariate Cox
regression models, high FGF23 levels were associated with increased fracture
incidence (adjusted HR = 2.97; 95% CI 1.18, 7.43). alpha-Klotho levels were
associated with bone formation but not resorption markers. In both univariate and
multivariable adjusted models, alpha-klotho levels were inversely associated with
the aortic-brachial pulse wave velocity ratio (beta = - 0.070; 95% CI - 0.133, -
0.006). CONCLUSIONS: These results suggest a role for FGF23/klotho axis on bone
and vascular metabolism in dialysis populations.
PMID- 29959499
TI - [Hybrid operating theater].
AB - A hybrid suite is an operating theater with imaging equipment equivalent to that
used in an angiography suite with computed tomography (CT) and magnetic resonance
imaging (MRI). They are often situated outside the operating room area and
typically serve as multifunctional rooms designed to support a variety of
catheter-based endovascular procedures and open surgery to be performed in the
same location. The possibility to perform these in the same location facilitates
the combination of both approaches to so-called hybrid procedures. Typical
clinical applications of hybrid suites are cardiac, thoracic and vascular
surgery, neurosurgery and neuroradiology, as well as orthopedics and
traumatology. Transcatheter aortic valve implantation (TAVI) is significantly
less invasive than a classical approach by open surgery. Patients older than 75
years with relevant comorbidities benefit most from the minimally invasive
interventional approach. There has been a paradigm shift in the management of
vascular diseases from open surgical repair to new percutaneous endovascular
interventions with good early outcomes. Of particular interest in this context is
the ability to block the part of the aorta proximal to the aneurysm with a
catheter-based dilatation balloon. Progress in image fusion technology and
intraoperative navigation has led to an increased acceptance of hybrid suites in
orthopedics and traumatology. The complex care of high-risk patients most often
outside the operating theater area is a challenge for the anesthesia team. This
demands meticulous planning on behalf of the anesthesiologist to ensure an
appropriate and safe strategy for anesthesia, intraoperative monitoring, vascular
access and the need for additional equipment. A thorough understanding of the
complexity of procedures is vital and a series of questions must be addressed:
what is needed to safely administer anesthesia in this environment? What
additional resources would be needed for an emergency situation? Is the patient
being kept safe from radiation hazards? Moreover, logistics may become an issue
as the hybrid suite is most often delocalized. In addition, many procedures
realized in a hybrid suite require a multidisciplinary approach and therefore
teamwork and professional communication are mandatory. Anesthesiologists need to
have an integral role in the hybrid suite team, understanding and anticipating
the risks for patients and leading the organization of workflow. The challenge in
anesthesia is to ensure that when patients are taken to these complex
environments the resources available enable high standards of care to be
provided. With future developments in imaging technology combined with more
powerful hardware and software, a far greater integration of all these imaging
and navigation technologies will be seen in future operating rooms. Finally,
patients are becoming more aware of medical developments via the world wide web
and increasingly request what they consider to be state of the art treatment.
PMID- 29959500
TI - [Performance of prehospital emergency anesthesia and airway management : An
online survey].
AB - BACKGROUND: The goal of rapid sequence induction (RSI) in cases of emergency
situations is to secure the airway as quickly as possible to prevent pulmonary
aspiration of gastric contents; however, the technique itself is not
standardized. For example, the choice of drugs, application of cricoid pressure
and the patient position remain controversial. A survey of emergency medical
services (EMS) physicians throughout Germany was carried out to assess the
different RSI techniques used and with respect to complying with the national
guidelines for emergency airway management anesthesia and local standard
operating procedures (SOP). MATERIAL AND METHODS: Between 1 April 2017 and 31 May
2017, EMS medical directors in Germany were contacted and asked to distribute a
28-question online questionnaire to local EMS physicians. Of the questions 26
were multiple choice and 2 with plain text. After 6 weeks an e-mail reminder was
sent. In addition, the survey was distributed via social media to EMS physicians.
RESULTS: In total the survey was opened 2314 times and 1074 completed responses
were received (completion rate 46%). Most of the participants were male (78%) and
anesthesiologists (70%) and only one quarter had a local SOP for RSI. The most
frequently used muscle relaxant was succinylcholine (62%) and over half of the
participants reported using cricoid pressure (57%). There was a distinction
between the specialist disciplines in the selection of drugs. Propofol was used
most by anesthesiologists, while the others still used etomidate on a larger
scale. Nearly 100% could fall back on supraglottic devices (one third laryngeal
mask, two thirds laryngeal tube) but only 32.8% with the recommended esophageal
drainage. A video laryngoscope was available to 51% of all EMS physicians
surveyed. CONCLUSION: The results of the survey demonstrate heterogeneity in RSI
techniques used by EMS physicians in Germany. Medical equipment and safe care
practices, such as labeling of syringes varied considerably between different
service areas. The recommendations of the S1 national guidelines on emergency
airway management and anesthesia should be adhered to together with the
implementation of local SOPs.
PMID- 29959501
TI - The peregrine falcon's rapid dive: on the adaptedness of the arm skeleton and
shoulder girdle.
AB - During a dive, peregrine falcons (Falco peregrinus) can reach a velocity of up to
320 km h- 1. Our computational fluid dynamics simulations show that the forces
that pull on the wings of a diving peregrine can reach up to three times the
falcon's body mass at a stoop velocity of 80 m s- 1 (288 km h- 1). Since the
bones of the wings and the shoulder girdle of a diving peregrine falcon
experience large mechanical forces, we investigated these bones. For comparison,
we also investigated the corresponding bones in European kestrels (Falco
tinnunculus), sparrow hawks (Accipiter nisus) and pigeons (Columba livia
domestica). The normalized bone mass of the entire arm skeleton and the shoulder
girdle (coracoid, scapula, furcula) was significantly higher in F. peregrinus
than in the other three species investigated. The midshaft cross section of the
humerus of F. peregrinus had the highest second moment of area. The mineral
densities of the humerus, radius, ulna, and sternum were highest in F.
peregrinus, indicating again a larger overall stability of these bones.
Furthermore, the bones of the arm and shoulder girdle were strongest in peregrine
falcons.
PMID- 29959498
TI - [Rapid sequence induction and intubation in patients with risk of aspiration :
Recommendations for action for practical management of anesthesia].
AB - BACKGROUND: Induction of general anesthesia in patients with risk for aspiration
needs special considerations to avoid the incidence and severity of
complications. Since no evidence-based guidelines support the challenge for
anesthesiologists various practical recommendations exist in clinical practice
for rapid sequence induction and intubation (RSI). The aim of this systematic
review is, to summarize the evidence and recommend a decision making process.
MATERIAL AND METHODS: Multilevel RAND-delphi-method (RAND: Research and
Development) combined with systematic literature research, individual assessment
and evaluation, consensus conferences and final common sequence. RESULTS AND
DISCUSSION: The consideration of all practical, clinical procedures in patients
at risk for aspiration represents an effective prevention of pulmonary aspiration
during the induction of anesthesia. These include the optimal drug pre-treatment
with antacids (e. g. sodium citrate) for highly aspiration-endangered and proton
pump inhibitors or H2 blockers in other patients the evening before. Each patient
should be examined and explained prior to RSI according to the recommendations of
the National German Society of Anesthesiology for preoperative evaluation. A RSI
should be performed in patients with no 2h liquid and no 6h food fasting or acute
vomiting, sub-ileus or ileus, or no protective reflexes or a gastrointestinal
passenger disorder. In addition, RSI should be performed in pregnant women after
the 3rd trimester and during birth. The expertise and competence of the physician
before and during rapid sequence induction and intubation about the respective
task distribution minimizes the risk of aspiration, as does the adequate
equipment, as well as an optimized upper body elevation of the patient.
Consistent pre-oxygenation with an FIO2 of 1.0 (FetO2-concentration > 0.9) and an
oxygen flow > 10 l/min using a completely sealing respiratory mask with
capnography should take 3-5 minutes. Fast enough deep anesthesia and muscle
relaxation to avoid coughing and choking can be achieved by a combination of
opioid, hypnotic and muscle relaxation. In addition, an opioid of choice,
propofol, thiopental, etomidate and ketamine can be used as hypnotic and
rocuronium with the availability of sugammadex should be used as muscle relaxant.
If there are no contraindications, succinylcholine can also be used as a muscle
relaxant. In case of an unexpected difficult airway, a 2nd generation
extraglottic airway device should be used. During regurgitation or aspiration,
intensive medical monitoring and fiber-optic bronchoscopy should be performed,
depending on the degree of severity and an X-ray thorax image or a CT scan should
be performed if symptoms arise. Three factors reduce the risk of aspiration:
expertise, support from an experienced anesthesiologist and close monitoring of
an inexperienced anesthesiologist.
PMID- 29959502
TI - Fragility fractures of the proximal femur: review and update for radiologists.
AB - Proximal femoral fragility fractures are common and result in significant
morbidity and mortality along with a considerable socioeconomic burden. The goals
of this article are to review relevant proximal femoral anatomy together with
imaging, classification, and management of proximal femoral fragility fractures,
and their most common complications. Imaging plays an integral role in
classification, management and follow-up of proximal femoral fragility fractures.
Classification of proximal femoral fragility fractures is primarily based on
anteroposterior hip radiographs. Pertinent imaging features for each category of
proximal femoral fractures that would guide management are: differentiating
nondisplaced from displaced femoral neck fractures, distinguishing stable from
unstable intertrochanteric fractures, and determining the morphology and
comminution of subtrochanteric fractures. Treatment of proximal femoral fragility
fractures is primarily surgical with either arthroplasty or internal fixation.
Intramedullary nailing is used in the treatment of some types of proximal femoral
fragility fractures and may be associated with unique complications that become
evident on postoperative follow-up radiographs.
PMID- 29959503
TI - The requirements of trainees and microsurgical skills.
PMID- 29959504
TI - Instrumented arthrodesis for non-traumatic craniocervical instability in very
young children.
AB - PURPOSE: Occipitocervical instrumentation is infrequently required for
stabilization of the axial and subaxial cervical spine in very young children.
However, when it is necessary, unique surgical considerations arise in children
when compared with similar procedures in adults. METHODS: The authors reviewed
literature describing fusion of the occipitocervical junction (OCJ) in toddlers
and share their experience with eight cases of young children (age less than or
equal to 4 years) receiving occiput to axial or subaxial spine instrumentation
and fixation. Diagnoses and indications included severe or secondary Chiari
malformation, skeletal dysplastic syndromes, Klippel-Feil syndrome, Pierre Robin
syndrome, Gordon syndrome, hemivertebra and atlantal occipitalization, basilar
impression, and iatrogenic causes. RESULTS: All patients underwent occipital bone
to cervical spine instrumentation and fixation at different levels. Constructs
extended from the occiput to C2 and T1 utilizing various permutations of titanium
rods, autologous rib autografts, Mersilene sutures, and combinations of
autografts with bone matrix materials. All patients were placed in rigid cervical
bracing or halo fixation postoperatively. No postoperative neurological deficits
or intraoperative vascular injuries occurred. CONCLUSION: Instrumented
arthrodesis can be a treatment option in very young children to address the non
traumatic craniocervical instability while reducing the need for prolonged
external halo vest immobilization. Factors affecting fusion are addressed with
respect to preoperative, intraoperative, and postoperative decision-making that
may be unique to the toddler population.
PMID- 29959505
TI - Polysomnography as an indicator for cervicomedullary decompression to treat
foramen magnum stenosis in achondroplasia.
AB - OBJECTIVE: Management of cervicomedullary compression due to foramen magnum
stenosis in achondroplasia remains controversial, especially for patients with no
symptoms or mild symptoms. We examined the effectiveness of polysomnography (PSG)
as an indicator for cervicomedullary decompression treatment. METHODS: We
retrospectively reviewed nine achondroplasia cases (mean age 1 year and 9 months)
treated from 2008 to 2015. All patients were examined by PSG, magnetic resonance
imaging (MRI), and otolaryngeal fibroscopy. We analyzed demographic data,
clinical presentation, degree and type of respiratory impairment, severity of
foramen magnum stenosis and concomitant cervicomedullary compression, treatment
(conservative or surgical), and clinical outcome. RESULTS: Eight of nine patients
presented with no severe symptoms in the daytime. However, MRI revealed four
severe, four moderate, and one mild case of cervicomedullary compression, and PSG
demonstrated severe sleep apnea in four cases and moderate sleep apnea in five
cases. All sleep apnea cases were obstructive or obstructive-dominant. Fibroscopy
revealed no upper airway stenosis in six cases and mild stenosis in three cases.
Four patients who had severe sleep-related respiratory disturbance on PSG and
severe or moderate cervicomedullary compression were treated by cervicomedullary
decompression. Three of these patients demonstrated improved sleep respiration
soon after surgery, while one required temporary tracheostomy due to bilateral
vocal cord paralysis caused by compression during intratracheal intubation.
CONCLUSION: Polysomnography can be a useful indicator for cervicomedullary
decompression surgery, especially in cases of seemingly asymptomatic
achondroplasia with severe foramen magnum stenosis.
PMID- 29959506
TI - Relationships between eyelid position and levator-superior rectus complex and
inferior rectus muscle in patients with Graves' orbitopathy with unilateral upper
eyelid retraction.
AB - PURPOSE: To assess the relationships between eyelid position and levator
palpebrae superioris (LPS)-superior rectus (SR) complex and inferior rectus (IR)
muscle volume in patients with Graves' orbitopathy (GO) with unilateral upper
eyelid retraction. METHODS: This was a cross-sectional observational study of 48
patients with GO with unilateral upper eyelid retraction. To measure muscle
volume, computerized tomography scans were performed, and 3D images were
analyzed. Digital photographs were taken, and vertical eyelid height was measured
using computed eyelid analysis software. The measured muscle volumes and eyelid
heights were assessed, and correlation analysis was performed. To verify the
parameters that are predictive for the presence of upper eyelid retraction,
receiver operating characteristic curves were analyzed, and logistic regression
was performed. RESULTS: The volume of the LPS/SR muscle complex in the eyes with
upper eyelid retraction was increased in 41 eyes (85.4%). The mean volume of the
LPS/SR complex was 0.92 +/- 0.40 cm3 in the eyes with upper eyelid retraction and
0.72 +/- 0.27 cm3 in the contralateral eyes (p < 0.0001). While there was no
correlation between LPS/SR complex volume and margin reflex distance1 (MRD1, the
vertical distance between the center of the pupil to the center of the upper
eyelid margin) (R = 0.024, p = 0.869), MRD1 and MRD2 (the vertical distance
between the center of the pupil and the center of the lower eyelid margin) in the
retracted eyes were negatively correlated (R = - 0.441, p = 0.002). In patients
with upper eyelid retraction without increased LPS/SR complex volume, IR volume
and MRD2 of the contralateral eye were 0.48 +/- 0.10 cm3 and 5.92 +/- 0.45 mm,
respectively. In the retracted eye, they were 0.37 +/- 0.17 cm3 and 5.32 +/- 0.59
mm, respectively (p = 0.018, and 0.028). Regression models incorporating LPS/SR
complex volume, MRD1, and lid lag could predict the presence of upper eyelid
retraction with an accuracy of 92.5%. CONCLUSIONS: In patients with GO, increased
LPS/SR complex volume in the retracted eye and increased IR volume of the
contralateral eye were both associated with unilateral upper eyelid retraction.
The combination of LPS/SR complex volume, MRD1, and lid lag can be used as a
reliable index of upper eyelid retraction in patients with GO.
PMID- 29959507
TI - Long-term follow-up of retinal nerve fiber layer cleavages in glaucoma patients
and suspects.
AB - PURPOSE: To investigate the structural and functional characteristics and change
of the retinal nerve fiber layer cleavages (RNFLCs) in glaucoma patients and
suspects in long-term follow-up. METHODS: This is a retrospective longitudinal
study. Within 43 eyes of 30 subjects, 62 RNFLC locations were detected on color
fundus photography. Basic ophthalmic examinations, color fundus photography,
optical coherence tomography (OCT), and visual field (VF) test were performed in
6-month intervals. Clinical characteristics and the structural and functional
changes of the cleaved areas were analyzed. RESULTS: RNFLC and localized
vitreoretinal traction occurred most commonly along the superotemporal retinal
vessel arcade. Nine locations had corresponding defects on OCT deviation map,
while 31 locations were associated with defects on OCT deviation map. Three
locations had corresponding VF defects. More of the non-highly myopic eyes had
lamellar hole than the highly myopes (p = 0.038). The RNFLC lesions in
glaucomatous eyes were more frequently associated with OCT defects on deviation
map (p = 0.021). There was no difference in the presence of lamellar hole or the
number of RNFLCs between the glaucomatous and non-glaucomatous eyes. During a
66.8 +/- 37.8-month follow-up, there was no structural or functional progression
of the RNFLCs as determined by color fundus photography, VF test, and GPA of OCT
interpreted by three ophthalmologists. There was no statistically significant
change of RNFLC area (p = 0.268). CONCLUSIONS: RNFLC did not show detectable
functional or structural change in early glaucoma patients and suspects after
long-term follow-up.
PMID- 29959509
TI - Brain functional imaging in obese and diabetic patients.
AB - Obesity and type 2 diabetes are associated with greater risk of brain damage.
Over the last decade, functional imaging techniques (functional magnetic
resonance imaging, fMRI, positron emission tomography, PET,
electroencephalography, magnetoencephalography, near infrared spectroscopy) have
been exploited to better characterize behavioral and cognitive processes, by
addressing cerebral reactions to a variety of stimuli or tasks, including
hormones and substrates (e.g., glucose, insulin, gut peptides), environmental
cues (e.g., presentation of sensory stimuli), and cognitive tasks. Among these
techniques, fMRI and PET are most commonly used, and this review focuses on
results obtained with these techniques in relation to brain substrate metabolism,
appetite control and food intake, and cognitive decline in obesity and type 2
diabetes. The available knowledge indicates that there are a series of cerebral
abnormalities associating with, or preceding obesity and type 2 diabetes,
including impaired substrate handling, insulin resistance, disruption of inter
organ cross-talk and of resting state networking. Some of these abnormalities are
reversed by metabolic interventions, suggesting that they are partly a
consequence rather than cause of disease. Therefore, causal implications and
mechanisms remain to be determined.
PMID- 29959510
TI - Optimal phase control of biological oscillators using augmented phase reduction.
AB - We develop a novel optimal control algorithm to change the phase of an oscillator
using a minimum energy input, which also minimizes the oscillator's transversal
distance to the uncontrolled periodic orbit. Our algorithm uses a two-dimensional
reduction technique based on both isochrons and isostables. We develop a novel
method to eliminate cardiac alternans by connecting our control algorithm with
the underlying physiological problem. We also describe how the devised algorithm
can be used for spike timing control which can potentially help with motor
symptoms of essential and parkinsonian tremor, and aid in treating jet lag. To
demonstrate the advantages of this algorithm, we compare it with a previously
proposed optimal control algorithm based on standard phase reduction for the Hopf
bifurcation normal form, and models for cardiac pacemaker cells, thalamic
neurons, and circadian gene regulation cycle in the suprachiasmatic nucleus. We
show that our control algorithm is effective even when a large phase change is
required or when the nontrivial Floquet multiplier is close to unity; in such
cases, the previously proposed control algorithm fails.
PMID- 29959508
TI - LeSPL-CNR negatively regulates Cd acquisition through repressing nitrate
reductase-mediated nitric oxide production in tomato.
AB - MAIN CONCLUSION: An SPL-type transcription factor, LeSPL-CNR, is negatively
involved in NO production by modulating SlNR expression and nitrate reductase
activity, which contributes to Cd tolerance. Cadmium (Cd) is a highly toxic
pollutant. Identifying factors affecting Cd accumulation in plants is a
prerequisite for minimizing dietary uptake of Cd from crops grown with
contaminated soil. Here, we report the involvement of a SQUAMOSA PROMOTER-BINDING
PROTEIN-LIKE (SPL) transcription factor LeSPL-CNR in Cd tolerance in tomato
(Solanum lycopersicum). In comparison with the wild-type Ailsa Craig (AC) plants,
the Colourless non-ripening (Cnr) epimutant displayed increased Cd accumulation
and enhanced sensitivity to Cd, which was in well accordance with the repression
of LeSPL-CNR expression. Cd stress-induced NO production was inhibited by nitrate
reductase (NR) inhibitor, but not NO synthase-like enzyme inhibitor. Expression
of LeSPL-CNR was negatively correlated with SlNR expression and the NR activity.
We also demonstrated that LeSPL-CNR inhibited the SlNR promoter activity in vivo
and bound to SlNR promoter sequence that does not contain a known SBP-binding
motif. In addition, expression of an IRON-REGULATED TRANSPORTER1, SlIRT1, was
more abundant in Cnr roots than AC roots under Cd stress. LeSPL-CNR may thus
provide a molecular mechanism linking Cd stress response to regulation of NR
dependent NO production, which then contributes to Cd uptake via SlIRT1
expression in tomato.
PMID- 29959511
TI - [Novel vitreous body replacement with hydrogel?]
AB - Although the surgical treatment of rhegmatogenous retinal detachment has
advanced, there still is a significant risk of redetachment and a slow visual
rehabilitation due to the use of endotamponades. Hydrophobic tamponades act via a
buoyancy vector causing an accumulation of proinflammatory cytokines opposite the
buoyancy vector. So far, the use of hydrophilic endotamponades is very promising
because they represent a possible solution for the abovementioned problems of
surgical ablation. This article presents the current developments in this field.
PMID- 29959512
TI - Reply to the letter to the editor.
PMID- 29959513
TI - Termination of pregnancy due to fetal central nervous system abnormalities
performed after 24 weeks' gestation: survey of 57 fetuses from a single medical
center.
AB - PURPOSE: To assess fetal central nervous system (CNS) abnormalities presenting as
major findings leading to late termination of pregnancy (late TOP) performed >=
24 weeks' gestation. METHOD: The study population included 2789 pregnant women
that underwent late TOP in our institute between the years 1998 and 2015.
RESULTS: Fifty-seven cases (2.0%) underwent late TOP because of fetal CNS
indications and are the subjects of the current study. Those cases were
subdivided into four categories (1) no routine prenatal screening with an
incidental finding discovered >= 24 weeks' gestation (25 patients, 43.8%); (2)
developmental or acquired findings detected during late second and third
trimester (22 patients, 38.6%); (3) apparently normal routine screening with
abnormal findings that could have been detected earlier (six patients, 10.6%);
(4) routine prenatal care raised suspicion of abnormalities, and the final
diagnosis was established only following additional tests (four patients, 7.0%).
CONCLUSIONS: Combining the two categories of CNS abnormalities, i.e., pregnant
women who did not undergo any fetal evaluation (group 1) and those that could
have been detected earlier (group 3) consists 54% from our cohort in which late
TOP could have been avoided. On contrary, 39% fetuses from our study population
had CNS developmental findings which could be detected only at advanced stage of
gestation.
PMID- 29959515
TI - Review of earlier evidence on dietary glycemic index and load and depression
needs further attention.
PMID- 29959514
TI - Finding sensitive parameters in internal dose calculations for
radiopharmaceuticals commonly used in clinical nuclear medicine.
AB - Internal dosimetry after incorporation of radionuclides requires standardized
biokinetic and dosimetric models. The aim of the present work was to identify the
parameters and the components of the models which contribute most to dosimetric
uncertainty. For this a method was developed allowing for the calculation of the
uncertainties of the absorbed dose coefficients. More specifically, the sampling
based regression method and the variance-based method were used to develop and
apply a global method of sensitivity analysis. This method was then used to
quantify the impact of various biokinetic and dosimetric parameters on the
uncertainty of internal doses associated with the incorporation of seven common
radiopharmaceuticals. It turned out that the correlation between biokinetic
parameters and time-integrated activity or calculated absorbed dose is strongest
when the source and target organ are identical, in accordance with the ICRP and
the MIRD approach. According to the ICRP approach, the parameter Fs which
describes the fractional distribution of any incorporated radioactivity to organ
S, has the greatest correlation with the time-integrated activity in the
corresponding source organ or with the calculated dose in the corresponding
target organ. In contrast, the MIRD approach suggested several biokinetic
parameters with similar correlation. The dosimetric parameters usually contribute
more to uncertainty in the calculated dose coefficients than the biokinetic
parameters, in both approaches. The results obtained are helpful for the revision
of biokinetic models for radiopharmaceuticals, because the most important
parameters in clinical applications can now be identified and investigated in
future studies.
PMID- 29959516
TI - Change in maximal fat oxidation in response to different regimes of periodized
high-intensity interval training (HIIT).
PMID- 29959517
TI - Mitigating the bilateral deficit: reducing neural deficits through residual force
enhancement and activation reduction.
AB - PURPOSE: The bilateral deficit (BLD) is characterized by a reduction in maximal
voluntary torque during a bilateral contraction relative to the sum of left and
right unilateral contractions. The BLD has been attributed to interhemispheric
inhibition as a result of unilateral torque differences between limbs. If the BLD
is the result of interhemispheric inhibition, lowering activation for a torque
matching task, as shown in residual force enhancement (RFE), may help overcome
the decrease in neural drive during bilateral contractions. Therefore, the
purpose of the present study was to determine whether RFE could reduce the BLD.
METHODS: Participants (n = 12) performed both isometric and RFE MVCs of the elbow
flexors under three conditions: (1) unilateral-left; (2) unilateral-right; and
(3) bilateral. To directly address the purpose of the study, a sub-group of
participants that displayed both RFE and a BLD ("Responders", n = 6) were
selected from the participant pool. RESULTS: "Responders" displayed RFE (7.1 +/-
5.3%) and an isometric BLD (BI: - 9.9 +/- 3.2%). In the RFE state, the BLD was no
longer significant (- 5.8 +/- 7.9%), accompanied by the elimination of
differences in biceps brachii EMG between arms (left: - 11.7 +/- 10.3%; right: -
11.5 +/- 13.2%), as seen during isometric contractions (left: - 12.0 +/- 23.2%;
right: - 21.1 +/- 16.6%). CONCLUSION: Residual force enhancement appears to
mitigate the BLD, alleviating the effects of a decrease in neural drive by
allowing more force for a given level of muscle activation when compared to a
purely isometric contraction.
PMID- 29959518
TI - Molecular detection of Cryptosporidium spp. and the occurrence of intestinal
parasites in fecal samples of naturally infected dogs and cats.
AB - Cats and dogs are hosts of a large number of gastrointestinal parasites and can
shed helminth eggs and protozoan oocysts in their feces. The close relationship
between companion animals and humans intensifies human exposure to zoonosis
caused by parasites. In this study, 177 fecal samples were collected: 128 from
dogs and 49 from cats of both sexes and varied ages. One or more intestinal
parasites were observed in 56.2% (72/128) of the dog fecal samples and in 53.0%
(26/49) of the cat fecal samples. Parasitic monoinfection was present in 70.8%
(51/72) of dog samples and in 46.1% (12/26) of cat samples, whereas multi
infection was observed in 29.2% (21/72) and 53.8% (14/26) of dog and cat samples,
respectively. The detection frequency of Cryptosporidium spp. was 22.6% (40/177)
using Ziehl-Neelsen staining. DNA was extracted from all samples and the
Cryptosporidium small subunit ribosomal ribonucleic acid (SSU rRNA) gene was
amplified from 5.6% (10/177) of the fecal samples using nested polymerase chain
reaction (PCR). Amplification was achieved in 4.6% (6/128) of the dog samples and
in 8.2% (4/49) of the cat samples. DNA sequencing of the nested PCR positive
samples identified Cryptosporidium canis in 66.6% (4/6) and Cryptosporidium
parvum in 33.3% (2/6) of the dog samples and Cryptosporidium felis in 75% (3/4)
and Cryptosporidium parvum in 25% (1/4) in the cat samples. The present study
thus demonstrated significant levels of gastrointestinal parasite infection in
companion animals and highlighted the presence of zoonosis agents.
PMID- 29959519
TI - What are the factors to affect outcome and healing of meniscus bucket handle
tears?
AB - INTRODUCTION: The purpose of this study is to identify patient, meniscus rupture
and surgical characteristics that influence the outcome and clinical healing
following operative repair of bucket handle tears. METHODS: Between 02/2006 and
10/2012, a total of 38 patients (14 women, 24 men) with bucket handle tears
underwent surgical meniscus repair. There were 27 isolated repairs and 11 with
concomitant anterior cruciate ligament (ACL) replacement. Patients were analyzed
on an average of 44.4 months (range 15-96 months) after surgery by the use of
standardized subjective scoring instruments [Lysholm, International Knee
Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score
(KOOS) and Tegner Activity Scale (TAS)]. To identify factors affecting the
outcome and suture survival, patient-specific, trauma-specific as well as
meniscus- and surgery-specific factors were collected. Patients were divided in
two groups with healed menisci (group 1) and re-rupture subjects (group 2).
Meniscus re-rupture was defined as a clinical failure. RESULTS: There were 25
patients with healed menisci and 13 (34.2%) that sustained re-rupture and
underwent either partial meniscectomy (n = 8) or re-suture (n = 5). Group 1
achieved slightly higher outcome compared to group 2 [Lysholm: 87.8 vs. 84.3 (p =
0.35), IKDC: 86.9 vs. 85.7 (p = 0.67), KOOS: 91.3 vs. 90.5 (p = 0.74)]. TAS was
better for group 2 [5.9 vs. 6.8 (p = 0.36)]. Strong impact to result in a
significantly increased outcome was identified for higher age, subjective knee
joint stability, high preoperative Lysholm Score, short trauma-to-repair time,
previous ACL reconstruction and a smaller number of sutures to fulfill meniscus
repair. Lower patient age, male gender and higher activity level had the
strongest impact to provoke re-rupture. CONCLUSION: Clinical outcome after
meniscus bucket handle suture is satisfying. Re-rupture rate among this
collective was 34.2%. Clear risk factors were identified for diminished clinical
healing and outcome.
PMID- 29959520
TI - Systematic reviews and meta-analysis in stone disease: is this what we need to
get stronger evidence?
PMID- 29959521
TI - Utility of Bronchoalveolar Lavage and Transbronchial Biopsy in Patients with
Hypersensitivity Pneumonitis.
AB - INTRODUCTION: Making the diagnosis of HP is challenging due to a lack of
consensus criteria and variability of both pathologic and radiographic findings.
The purpose of this retrospective study was to determine the diagnostic utility
of the combination of BAL lymphocyte count and TBBX in patients with HP. METHODS:
We conducted a retrospective cohort study of all patients with a MDD diagnosis of
HP at a single center. RESULTS: 155 patients were included in the study. 49% of
patients who underwent BAL had a lymphocyte count > 20, 42% had a lymphocyte
count > 30, and 34% had lymphocyte count > 40%. The median BAL lymphocyte count
was higher in inflammatory HP compared to fibrotic HP. The addition of TBBX to
BAL significantly increased the diagnostic yield regardless of the BAL lymphocyte
cutoff used. The yield of bronchoscopy with TBBX and BAL when a lymphocyte count
> 40% was used as a cutoff was 52%. CONCLUSIONS: Our study suggests that the
combination of TBBX with BAL significantly increases the likelihood that the
procedure will provide adequate additional information to allow a confident MDD
diagnosis of HP and may reduce the need for SLB in the diagnostic workup of HP.
PMID- 29959522
TI - Laparoscopic versus open emergent ventral hernia repair: utilization and outcomes
analysis using the ACSNSQIP database.
AB - INTRODUCTION: Laparoscopic ventral hernia repair (VHR) is associated with
decreased morbidity and shorter length of stay (LOS) when compared to open VHR.
Despite evidence of the benefits of laparoscopy, its utilization in VHR has
lagged behind that of other complex surgical procedures. We hypothesized that
utilization is further reduced in emergency cases. The aim of this study was to
evaluate the utilization of laparoscopy in emergent VHR and to assess 30-day
outcomes for patients undergoing laparoscopic emergent ventral hernia repair
(LEVHR) versus open emergent ventral hernia repair (OEVHR). METHODS: We used the
ACS-NSQIP database for years 2006-2015 to compare LEVHR versus OEVHR. Inclusion
required two factors: (1) classification as an emergency case and (2) primary
procedure documented as laparoscopic or open repair of incarcerated umbilical,
ventral, or incisional hernia. LOS and 30-day morbidity and mortality were
assessed. RESULTS: A total of 13,126 patients underwent emergent repair of
initial or recurrent umbilical, ventral, or incisional hernia. 1130 (8.6%)
underwent LEVHR repair and 11,996 (91.4%) underwent OEVHR. Patient demographic
data display a trend toward decreased utilization of laparoscopy in patients with
more significant comorbidities. LEVHR was associated with decreased operative
time and postoperative LOS. LEVHR was associated with decreased superficial
surgical site infection (SSI), deep SSI, and 30-day mortality. Subgroup analysis
displays decreased incidence of superficial SSI, deep SSI, wound disruption,
pneumonia, and postoperative sepsis for patients ASA1-3 undergoing LEVHR versus
OEVHR. CONCLUSION: Utilization of laparoscopy in VHR is low in emergency cases.
Patients who did undergo LEVHR had decreased postoperative LOS and decreased
infectious and wound-related morbidity. Increased utilization in emergency VHR
could significantly improve patient outcomes. Further study is warranted.
PMID- 29959523
TI - Laparoscopic surgery for large left lateral liver tumors: safety and oncologic
outcomes.
AB - BACKGROUND: Although laparoscopic hepatectomy has been proven to be safe and
reliable, the influence of tumor size on the feasibility of laparoscopic left
lateral segmentectomy (LLLS) is unclear. We retrospectively reviewed our surgical
results focusing on hepatic tumor located in the left lateral segment. METHODS:
From January 2003 to June 2016, patients who underwent left lateral segmentectomy
were retrospectively reviewed, and data were collected on patient
characteristics, peri-operative outcomes, and pathologic results. Patients with
intrahepatic stone, cystic lesion, or unmeasurable tumor size were excluded. The
continuous variables were compared using the Mann-Whitney U test and categorical
variables using the Chi square or Fisher's exact test. The overall and disease
free survival rates were computed using the Kaplan-Meier method and compared
using the log-rank test. RESULTS: A total of 103 patients were enrolled for
analysis. Among the patients with tumors larger than 5 cm in the left lateral
segment, those who underwent laparoscopic surgery had significantly shorter
hospital stay and larger resection margin than those who underwent open surgery.
The surgical results of the patients who underwent LLLS were not significantly
different from those of the patients with tumors larger than 5 cm. Specifically,
the 5-year overall survival and disease-free survival rates of the patients with
hepatocellular carcinoma (HCC) larger than 5 cm who underwent LLLS were
comparable to those of the patients who underwent open left lateral
segmentectomy. CONCLUSIONS: LLLS is safe and also feasible for hepatic tumors
larger than 5 cm. For HCCs larger than 5 cm, the laparoscopic approach yields
satisfying oncologic outcomes as the open approach.
PMID- 29959524
TI - Job strain, long work hours, and suicidal ideation in US workers: a longitudinal
study.
AB - PURPOSE: To investigate whether chronic psychosocial work stressors (low job
control, high job demands, job strain, low supervisor and coworker support, job
insecurity, and long work hours) are longitudinally associated with suicidal
ideation in a working population. METHODS: Five-hundred seventy-eight workers
(aged 34-69) were chosen for this analysis from those who participated in both
project 1 (2004-2006 at baseline) and project 4 (2004-2009 at follow-up) of the
Midlife Development in the United States II study. The median time interval
between the two projects was 26 months (range 2-62 months). RESULTS: About 11% of
the workers reported suicidal ideation at follow-up, while 3% of them reported
moderate/severe suicidal ideation at follow-up. After controlling for age,
marital status, race, family history of suicide, and suicidal ideation at
baseline, low skill discretion and job strain (a combination of low job control
and high job demands) were associated with total suicidal ideation. After
excluding those with suicidal ideation at baseline from analysis and further
controlling for other work stressors, job strain was strongly associated with
moderate/severe suicidal ideation: ORs, 4.29 (1.30-14.15) for quartile-based job
strain and 3.77 (1.21-11.70) for median-based job strain. Long work hours (> 40
h/week vs. <= 40 h/week) also increased the likelihood for moderate/severe
suicidal ideation: OR 4.06 (1.08-15.19). CONCLUSIONS: Job strain and long work
hours were longitudinally associated with moderate/severe suicidal ideation.
Increasing job control and ensuring optimal level of work demands, including 40 h
or less of work per week may be an important strategy for the prevention of
suicide in working populations.
PMID- 29959525
TI - Accuracy of an internet-based speech-in-noise hearing screening test for high
frequency hearing loss: incorporating automatic conditional rescreening.
AB - PURPOSE: To validate the accuracy of an internet-based speech-in-noise hearing
screening test for high-frequency hearing loss (HFHL) 'Occupational Earcheck
(OEC)' incorporating an automatic conditional rescreening, in an occupationally
noise-exposed population. Secondary objectives were to assess the effects of age
on test accuracy measures, and to assess the test accuracy for different degrees
of HFHL. METHODS: A study was conducted on cross-sectional data of occupational
audiometric examinations, including the index test OEC and reference standard
pure-tone air conduction audiometry, of 80 noise-exposed workers. Sensitivity,
specificity, and likelihood ratios were calculated for the OEC, after automatic
conditional rescreening, for a younger and an older age group, and for two
degrees of HFHL (HFHL25: PTA3,4,6 >= 25 dB HL, and HFHL35: PTA3,4,6 >= 35 dB HL,
both for at least one ear). RESULTS: Test specificity for HFHL25 after a single
test was 63%, and improved to 93% after the automatic conditional rescreen. Test
sensitivity for HFHL25 decreased from 65% to 59%. Test sensitivity and
specificity including automatic conditional rescreening for HFHL35 was 94% and
90%, respectively. The positive likelihood ratio for HFHL25 was 8.4, and for
HFHL35 9.4. The negative likelihood ratio for HFHL35 was below 0.1. CONCLUSIONS:
The OEC is an appropriate screening test, especially for HFHL35. Normal-hearing
workers who obtained a positive test result for the first test for one or two
ears, benefit from having an automatic rescreen, resulting in an improvement of
the test specificity, and hence prevent unnecessary referral.
PMID- 29959526
TI - Correction to: S(+)-ketamine : Current trends in emergency and intensive
caremedicine.
AB - Correction to: Wien Klin Wochenschr 2017 https://doi.org/10.1007/s00508-017-1299
3 The article S(+)-ketamine Current trends in emergency and intensive
caremedicine, written by Helmut Trimmel, Raimund Helbok, Thomas Staudinger,
Wolfgang Jaksch, Brigitte Messerer, Herbert Schochl and Rudolf Likar, was ....
PMID- 29959527
TI - Diagnosis of Helicobacter pylori infection : A short review.
AB - Helicobacter pylori infections represent an important factor in the pathogenesis
of chronic gastritis, peptic ulcer, MALT lymphoma and gastric adenocarcinoma. The
recently published Maastricht V/Florence consensus report indicated that the urea
breath test using 13 C urea still remains the best non-invasive test to diagnose
H. pylori infections with high sensitivity and specificity. Among the stool
antigen tests, the ELISA monoclonal antibody test is a rational option. Effective
therapy should be based only on susceptibility testing in regions with documented
high clarithromycin resistance (>15%). Advanced high-resolution endoscopic
technologies enable increased diagnostic accuracy for detection of H. pylori
infections.
PMID- 29959528
TI - Association between cancer risk and polycyclic aromatic hydrocarbons' exposure in
the ambient air of Ahvaz, southwest of Iran.
AB - Nowadays, a large number of health endpoints such as disease rates, treatment
costs, and death, by air pollutants, have been a serious health problem for
humans. One of the most hazardous air pollutants, which is highly dangerous for
human health, is polycyclic aromatic hydrocarbons (PAHs). The existence of the
emission of industries' pollutants and seasonal variations are the primary agents
affecting PAHs' concentration. The purposes of this study were to calculate the
cancer risk and measure PAHs' exposure in the ambient air of Ahvaz, southwest of
Iran, during 2017. Three distinct areas ((S1) industrial, (S2) high traffic, and
(S3) residential) of Ahvaz metropolitan were selected. Omni sampler equipped with
polytetrafluoroethylene (PTFE) filters were used for active sampling of PAHs. To
detect the level of PAHs, gas chromatography with mass spectrometry (GC/MS) was
used. Incremental lifetime cancer risk (ILCR) and lifetime average daily dose
(LADD) were used to estimate the health risk caused by PAHs. The results showed
that the residential and industrial areas had the lowest and highest level of
PAHs. Moreover, the average levels of PAHs in industrial, high traffic, and
residential areas were 8.44 +/- 3.37, 7.11 +/- 2.64, and 5.52 +/- 1.63 ng m-3,
respectively. Furthermore, ILCR in autumn and winter was higher than EPA
standard, 0.06307 and 0.04718, respectively. In addition, ILCR in different areas
was significantly higher than standard. Research findings imply that the levels
of exposure to PAHs can increase ILCR and risk of health endpoint. The cancer
risk attributed to PAHs should be further investigated from the perspective of
the public health in metropolitans.
PMID- 29959530
TI - Persistent hypoglycemic attacks during hemodialysis sessions in an infant with
congenital nephrotic syndrome: Questions.
PMID- 29959529
TI - Anxiety, depression, and inflammation after restorative proctocolectomy.
AB - PURPOSE: Anxiety and depression (A&D) are more common in inflammatory bowel
disease (IBD) and in IBD patients who undergo proctocolectomy with ileal pouch
anal anastomosis (IPAA). Our aim was to test the hypothesis that chronic
inflammatory conditions in IPAA are associated with increased incidence of A&D.
METHODS: Retrospective cohort study at a single tertiary care referral center
using a consented IBD and colon cancer natural history registry. Demographic and
clinical factors, including surgical and psychiatric history, were abstracted.
RESULTS: We compared A&D rate in three cohorts: (1) ulcerative proctocolitis with
IPAA (UC) (n = 353), (2) Crohn's disease/indeterminate proctocolitis with IPAA
(CDIC) (n = 49), and (3) familial adenomatous polyposis with IPAA (FAP) (n = 33).
Forty-six CDIC patients (93.9%) demonstrated pouch-related inflammation, while
126 UC patients (35.7%) and 2 FAP patients (6.1%) developed pouchitis. CDIC had a
higher rate of A&D co-diagnosis compared to UC and FAP (20.4 vs.12.7 vs.12.1%
respectively; p < 0.05). UC patients with pouchitis also exhibited a higher rate
of A&D than UC without pouchitis (19.8 vs.8.8%; p < 0.05). Multivariable analysis
demonstrated that pre-operative corticosteroid use (OR = 4.46, CI = 1.34-14.87, p
< 0.05), female gender (OR = 2.19, CI = 1.22-3.95, p < 0.01), tobacco use (OR =
2.92, CI = 1.57 = 5.41, p < 0.001), and pouch inflammation (OR = 2.37, CI = 1.28
4.39, p < 0.05) were each independently associated with A&D in these patients.
CONCLUSIONS: Anxiety and depression were more common in patients experiencing
inflammatory conditions of the pouch. UC without pouchitis and FAP patients
demonstrated lower rates of A&D (that were comparable to the general population),
implying that having an IPAA alone was not enough to increase risk for A&D.
Factors independently associated with A&D in IPAA included an inflamed pouch,
corticosteroid use, smoking, and female gender.
PMID- 29959531
TI - Should mycophenolate mofetil be administered prior to cyclosporine A as a steroid
sparing agent to children with steroid-dependent nephrotic syndrome?
PMID- 29959532
TI - Prenatal hyperechogenic kidneys in three cases of infantile hypercalcemia
associated with SLC34A1 mutations.
AB - BACKGROUND: Prenatal diagnosis of hyperechogenic kidneys is associated with a
wide range of etiologies and prognoses. The recent advances in fetal ultrasound
associated with the development of next-generation sequencing for molecular
analysis have enlarged the spectrum of etiologies, making antenatal diagnosis a
very challenging discipline. Of the various known causes of hyperechogenic fetal
kidneys, calcium and phosphate metabolism disorders represent a rare cause. An
accurate diagnosis is crucial for providing appropriate genetic counseling and
medical follow-up after birth. METHODS: We report on three cases of fetal
hyperechogenic kidneys corresponding to postnatal diagnosis of nephrocalcinosis.
In all cases, antenatal ultrasound showed hyperechogenic kidneys of normal to
large size from 22 gestational weeks, with a normal amount of amniotic fluid.
Postnatal ultrasound follow-up showed nephrocalcinosis associated with
hypercalcemia, hypercalciuria, elevated 1,25(OH)2-vitamin D, and suppressed
parathyroid hormone levels. RESULTS: Molecular genetic analysis by next
generation sequencing performed after birth in the three newborns revealed
biallelic pathogenic variants in the SLC34A1 gene, encoding the sodium/phosphate
cotransporter type 2 (Npt2a), confirming the diagnosis of infantile
hypercalcemia. CONCLUSIONS: Nephrocalcinosis due to infantile hypercalcemia can
be a cause of fetal hyperechogenic kidneys, which suggests early antenatal
anomaly of calcium and phosphate metabolism. This entity should be considered in
differential diagnosis. Postnatal follow-up of infants with hyperechogenic
kidneys should include evaluation of calcium and phosphate metabolism.
PMID- 29959533
TI - Persistent hypoglycemic attacks during hemodialysis sessions in an infant with
congenital nephrotic syndrome: Answers.
PMID- 29959534
TI - Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin,
a DPPIV inhibitor, prevents progression of steatohepatitis in a murine model of
non-alcoholic steatohepatitis with diabetes.
AB - Non-alcoholic steatohepatitis (NASH) is characterized by the presence of hepatic
steatosis, oxidative stress, inflammation, and hepatocyte injury with or without
fibrosis. In this study, we explored the effect of APD668, a GPR119 agonist alone
or in combination with linagliptin, a DPPIV inhibitor, on the progression of
steatohepatitis in a murine model of NASH with diabetes. A novel NASH model with
diabetes was generated by administration of streptozotocin injection to neonatal
C57BL/6 mice (2-3 days old) combined with a high-fat diet feeding from the age of
4 weeks. The plasma biochemical parameters, oxidative stress, inflammation and
histopathological changes were assessed. APD668 alone showed reduction in plasma
glucose (- 39%, P < 0.05) and triglyceride level (- 26%) whereas a combined
treatment of APD668 with linagliptin resulted in a more pronounced reduction in
plasma glucose (- 52%, P < 0.001) and triglyceride (- 50%, P < 0.05) in NASH
mice. In addition, co-administration of APD668 with linagliptin demonstrated a
significant decrease in hepatic triglyceride, NAS score, hepatic TBARS and
hepatic TNF-alpha in NASH mice with diabetes. These findings suggest that GPR119
receptor agonists in combination with DPPIV inhibitors may represent a promising
therapeutic strategy for the treatment of NASH.
PMID- 29959535
TI - Evaluating the Privacy Policies of Mobile Personal Health Records for Pregnancy
Monitoring.
AB - A mobile personal health record (mPHR) for pregnancy monitoring allows the
pregnant woman to track and manage her personal health data. However, owing to
the privacy and security issues that may threaten the exchange of this sensitive
data, a privacy policy should be established. The aim of this study is to
evaluate the privacy policies of 19 mPHRs for pregnancy monitoring (12 for iOS
and 7 for Android) using a template covering the characteristics of privacy,
security, and standards and regulations. The findings of this study show that
none of the privacy policies evaluated entirely comply with the characteristics
studied. The developers of mPHRs for pregnancy monitoring are, therefore,
requested to improve and pay more attention to the structure and the content of
the privacy policies of their apps.
PMID- 29959536
TI - Automated Anatomic Labeling Architecture for Content Discovery in Medical Imaging
Repositories.
AB - The combination of textual data with visual features is known to enhance medical
image search capabilities. However, the most advanced imaging archives today only
index the studies' available meta-data, often containing limited amounts of
clinically useful information. This work proposes an anatomic labeling
architecture, integrated with an open source archive software, for improved
multimodal content discovery in real-world medical imaging repositories. The
proposed solution includes a technical specification for classifiers in an
extensible medical imaging archive, a classification database for querying over
the extracted information, and a set of proof-of-concept convolutional neural
network classifiers for identifying the presence of organs in computed tomography
scans. The system automatically extracts the anatomic region features, which are
saved in the proposed database for later consumption by multimodal querying
mechanisms. The classifiers were evaluated with cross-validation, yielding a best
F1-score of 96% and an average accuracy of 97%. We expect these capabilities to
become common-place in production environments in the future, as automated
detection solutions improve in terms of accuracy, computational performance, and
interoperability.
PMID- 29959537
TI - A necessary distinction between spatial representativeness of an air quality
monitoring station and the delimitation of exceedance areas.
AB - The European legislation on ambient air quality introduces the concepts of
spatial representativeness of a monitoring station and spatial extent of an
exceedance zone. Spatial representativeness is an essential macro-scale siting
criterion which should be evaluated before the setting-up and during the life of
a monitoring point. As for the exceedance area, it has to be defined each time an
environmental objective is exceeded in an assessment zone. No specific approach
is prescribed to delimit such areas. A probabilistic methodology is presented,
based on a preliminary kriging estimation of atmospheric concentrations at each
point of the domain. It is applied to NO2 pollution on the urban scale. In the
proposed approach, a point belongs to the area of representativeness of a station
if its concentration differs from the station measurement by less than a given
threshold. To take the estimation uncertainty into account, the standard
deviation of the kriging error is used in a probabilistic framework. The choice
of the criteria used to deal with overlapping areas is first tested on NO2 annual
mean concentration maps of France, built by combining surface monitoring
observations and outputs from the CHIMERE chemistry transport model. At the local
scale, data from passive sampling surveys and high -resolution auxiliary
variables are used to provide a more precise estimation of the background
pollution in different French cities. The traffic-related pollution can also be
accounted for in the map by additional predictors such as distance to the road,
and traffic-related NOx emissions. Similarly, the proposed approach is
implemented to identify the points, at a given statistical risk, where the NO2
concentration is above the annual limit value.
PMID- 29959538
TI - Isotopic evidence for niche partitioning and the influence of anthropogenic
disturbance on endemic and introduced rodents in central Madagascar.
AB - We applied a multi-isotope approach to examine aspects of niche partitioning,
competition, and mobility for rodents in the Central Highlands of Madagascar.
Specifically, we used carbon (delta13C), nitrogen (delta15N), and strontium
(87Sr/86Sr) isotope ratios in bone to investigate diet and mobility for endemic
tufted tail rats (Eliurus spp.), and introduced black rats (Rattus rattus) and
house mice (Mus musculus) within and outside a fragment of montane humid forest
in the Ambohitantely Special Reserve. There was a clear spatial segregation in
trapping success for different species: Eliurus was only in the forest interior
and edge, Mus only outside of the fragment in a marsh and park housing complex,
and Rattus in all habitats except the housing complex. We find only moderate
support for mobility of rodents among habitats. Mus may routinely move between
the marsh and housing complex. However, regular movement between the forest edge
and interior, or between the forest fragment and surrounding grassland is not
supported. Taxa appear to target different foods: Rattus tends to feed at a
higher trophic level than Eliurus, and Mus consumes some C4 resources. To date,
strontium isotopes have been underutilized in ecological research. Here, we show
that they are highly complementary to carbon and nitrogen isotope data. Even in
localities with relatively uniform underlying geology, it may be possible to
distinguish individuals that regularly forage in different habitats.
PMID- 29959539
TI - Feature Selection for Automatic Tuberculosis Screening in Frontal Chest
Radiographs.
AB - To detect pulmonary abnormalities such as Tuberculosis (TB), an automatic
analysis and classification of chest radiographs can be used as a reliable
alternative to more sophisticated and technologically demanding methods (e.g.
culture or sputum smear analysis). In target areas like Kenya TB is highly
prevalent and often co-occurring with HIV combined with low resources and limited
medical assistance. In these regions an automatic screening system can provide a
cost-effective solution for a large rural population. Our completely automatic TB
screening system is processing the incoming CXRs (chest X-ray) by applying image
preprocessing techniques to enhance the image quality followed by an adaptive
segmentation based on model selection. The delineated lung regions are described
by a multitude of image features. These characteristics are than optimized by a
feature selection strategy to provide the best description for the classifier,
which will later decide if the analyzed image is normal or abnormal. Our goal is
to find the optimal feature set from a larger pool of generic image features,
used originally for problems such as object detection, image retrieval, etc. For
performance evaluation measures such as under the curve (AUC) and accuracy (ACC)
were considered. Using a neural network classifier on two publicly available data
collections, -namely the Montgomery and the Shenzhen dataset, we achieved the
maximum area under the curve and accuracy of 0.99 and 97.03%, respectively.
Further, we compared our results with existing state-of-the-art systems and to
radiologists' decision.
PMID- 29959540
TI - The fractal dimension of a conspicuous ornament varies with mating status and
shows assortative mating in wild red-legged partridges (Alectoris rufa).
AB - Complex body designs, such as plumage ornaments in birds, can be described by
fractal geometry. These complex patterns could have a role as visual signals
during courtship and social interactions, but an empirical validation in the wild
is currently lacking. Here, we investigated whether the fractal dimension (FD) of
a complex plumage pattern displayed by red-legged partridges Alectoris rufa could
function as a potential sexual signal. We captured wild birds early in the
breeding season and tested if mated and unmated birds differed in the FD of their
conspicuous melanin-based black bib. We also tested if the FD of the black bib
was correlated within the pair, looking for evidence of assortative mating based
on the expression of this trait. We simultaneously assessed similar effects in
other ornamental traits (black bib size, white throat patch and black flank band
surface, redness of the eye rings and bill). Mated birds showed higher black bib
FD values than unmated ones. Mated males, but not females, also displayed a
larger black bib. Moreover, the black bib FD (but not the trait size) and the
white throat patch surface showed assortative mating. Finally, females with
higher black bib FD showed smaller black flank band surface, suggesting a trade
off in the expression of the two melanin-pigmented plumage traits. This provides
unique and novel indication for the shape complexity of a pigmented trait, here
described by its fractal dimension, to be potentially under sexual selection in a
wild animal.
PMID- 29959541
TI - Travel and the Spread of Drug-Resistant Bacteria.
AB - PURPOSE OF REVIEW: The rise in antimicrobial resistance is an urgent public
health threat which, in the absence of intervention, may result in a post
antibiotic era limiting the effectiveness of antibiotics to treat both common and
serious infections. Globalization and human migration have profoundly contributed
to the spread of drug-resistant bacteria. In this review, we summarize the recent
literature on the importance of travelers in the spread of drug-resistant
bacterial organisms. Our goal was to describe the importance of travel on a
variety of clinically relevant drug-resistant bacterial organisms including
extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem
resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus,
Salmonella species, as well as other enteric infections. RECENT FINDINGS:
Travelers from high income countries, visiting low and middle income countries,
frequently acquire drug-resistant bacteria, particularly extended-spectrum beta
lactamase-producing Enterobacteriaceae. The highest risk is associated with
travel to the Indian subcontinent. Multidrug-resistant enteric infections in
travelers from Salmonella spp., Campylobacter spp., and Shigella spp. are
increasing. Refugees, pilgrimages, and medical tourists are associated with
considerable risk of multiple forms of drug resistance. This review highlights
the importance of antimicrobial stewardship, infection control, and surveillance;
particularly in low and middle income countries. International leadership with
global coordination is vital in the battle against antimicrobial resistance.
PMID- 29959543
TI - Advancing Agrobacterium-Based Crop Transformation and Genome Modification
Technology for Agricultural Biotechnology.
AB - The last decade has seen significant strides in Agrobacterium-mediated plant
transformation technology. This has not only expanded the number of crop species
that can be transformed by Agrobacterium, but has also made it possible to
routinely transform several recalcitrant crop species including cereals (e.g.,
maize, sorghum, and wheat). However, the technology is limited by the random
nature of DNA insertions, genotype dependency, low frequency of quality events,
and variation in gene expression arising from genomic insertion sites. A majority
of these deficiencies have now been addressed by improving the frequency of
quality events, developing genotype-independent transformation capability in
maize, developing an Agrobacterium-based site-specific integration technology for
precise gene targeting, and adopting Agrobacterium-delivered CRISPR-Cas genes for
gene editing. These improved transformation technologies are discussed in detail
in this chapter.
PMID- 29959542
TI - Dynamic behavior and selective adsorption of a methanol/water mixture inside a
cyclic peptide nanotube.
AB - Present molecular dynamics simulations indicate that the methanol component in a
methanol/water mixture is more likely to be trapped in a cyclic peptide nanotube
(CPNT), while water molecules tend to be present at the channel mouths as
transient guests. Channel water resides mainly between methanol and the CPNT
wall, resulting in a distinct decrease in the H-bond number per channel methanol.
Six designed CPNTs with different channel diameters and outer surface
characteristics all possess distinct selectivity to methanol over water. Of
these, the amphipathic 8 * (AQ)4-CPNT exhibits the best performance. Results in
this study provide basic information for the application of a CPNT to enrich
methanol from a methanol/water mixture. Graphical Abstract Typical overview of
water and methanol molecular distribution in cyclic peptide nanotubes.
PMID- 29959544
TI - GIAO-DFT-NMR characterization of fullerene-cucurbituril complex: the effects of
the C60@CB[9] host-guest mutual interactions.
AB - Magnetic shielding constants for an isolated fullerene C60, cucurbituril CB[9],
and the host-guest complex C60@CB[9] were calculated as a function of separation
of the monomers. Our results in the gas phase and water indicate a significant
variation of the magnetic properties for all atoms of the monomers in the complex
and after liberation of fullerene C60 from the interior of the CB[9] cavity. The
interaction between the two monomers results in a charge transfer that
collaborates with a redistribution of electron density to deshield the monomers.
Graphical Abstract NMR spectroscopy alteration on C60@CB[9] host-guest mutual
interactions?.
PMID- 29959545
TI - The Current State of Antimicrobial Stewardship: Challenges, Successes, and Future
Directions.
AB - PURPOSE OF REVIEW: The aim of this study is to examine the current state of the
field of antimicrobial stewardship (AS) by highlighting key challenges and
successes, as well as exciting future directions. RECENT FINDINGS: AS mandates
from the Centers for Medicare and Medicaid (CMS) and the Joint Commission (TJC)
will stimulate increased compliance with current AS standards, but overall
compliance is currently poor. Key challenges to progress in the field of AS
include insufficient workforce and monetary resources, poorly defined AS metrics,
and much needed expansion beyond the inpatient hospital setting. Despite these
challenges, massive progress has been made in the last two and a half decades
since the field of AS emerged. AS metrics are rapidly evolving and transforming
the way antimicrobial stewardship programs (ASPs) measure success. Rapid
diagnostics and diagnostic test stewardship are proving to be extremely effective
when coupled with an ASP. Telehealth may improve access to ASP expertise in
resource poor settings, and the role of bedside nurses as ASP team members has
the potential to greatly augment ASP efforts. Allergy testing as an ASP strategy
remains largely underutilized. ASPs have made significant gains in the battle
against antimicrobial resistance (AR), but considerable advancement is still
needed. Awareness of current challenges is critical to ensure progress in the
field. The field of AS is expanding and transforming rapidly through integration,
technology, and improved processes.
PMID- 29959546
TI - Ureaplasma urealyticum: the Role as a Pathogen in Women's Health, a Systematic
Review.
AB - PURPOSE OF REVIEW: To evaluate the role of Ureaplasma urealyticum as a genital
pathogen in women's health. Three aspects were analyzed: (1) preterm delivery
(PTD); (2) female infertility; and (3) lower genital tract pathology including
pelvic inflammatory disease (PID), cervicitis, and genital discomfort (discharge,
burning). RECENT FINDINGS: A systematic review was performed. Searching PUBMED
and EMBASE for published articles from January 2003 to September 2017 using the
key word "Ureaplasma urealyticum" yielded 1835 manuscripts. These were further
screened using defined inclusion criteria: (1) original peer-reviewed
observational studies; (2) English language; (3) U. urealyticum was specifically
isolated; (4) present "cases"/"exposed" and "controls"/"unexposed" to enable
calculating an association between U. urealyticum and the outcome studied.
Altogether, 32 studies were included that underwent quality scoring based on
methodology, sample size, study population, and method of identification of U.
urealyticum. The association of U. urealyticum and PTD was inconsistent between
the studies. Eight of the ten prospective studies failed to show an association
between U. urealyticum and PTD, yet four of the six case control studies found a
positive association. Regarding female infertility and genital discomfort, five
of the six studies for each of these topics failed to find an association. Only
two studies met the inclusion criteria for cervicitis with conflicting
conclusions. Unfortunately, none of the studies met the inclusion criteria for
PID. It seems that U. urealyticum has a limited role as a pathogen in female
infertility, cervicitis, PID, and genital discomfort. The role as a pathogen in
PTD is unclear and future studies are needed to address this issue.
PMID- 29959547
TI - Reduction of sludge formed during a coagulation treatment of Ridomil Gold by
means of non-thermal quenched plasma pre-treatment.
AB - Chemical coagulation and adsorption, despite many drawbacks, are actually the
main techniques used for the removal of pollutants from aqueous solution;
however, these techniques are becoming ineffective due to the exponential
increase in the amount and complexity of discharged pollutants; thus, the sludge
treatment process became a more complex challenge. The present study focuses on
the way to reduce the quantity of sludge formed during the removal of Ridomil
Gold, a widely used pesticide-fungicide in agriculture. Results revealed that pre
treatment of initial waste solution by the gliding arc (Glidarc), a source of non
thermal plasma, leads to a significant reduction of the sludge formed during the
coagulation treatment. For a 20-min pre-treated effluent Glidarc followed by
chemical coagulation, there was a reduction in the volume of sludge formed in the
order of 90 and 80% for alum and ferric sulfate coagulants respectively without
reducing the performance of pesticide removal. Therefore, there is a positive
synergism between treatment by chemical coagulation and plasma treatment. These
results suggest that the Glidarc can be an effective solution for the reduction
of sludge obtained during treatment by coagulation.
PMID- 29959548
TI - Evolving Epidemiology of Japanese Encephalitis: Implications for Vaccination.
AB - PURPOSE OF REVIEW: We examine the present global burden of Japanese encephalitis
(JE) in endemic populations, summarize published cases in travelers since 2009,
examine current guidelines for vaccination for international travelers, and
consider challenges in prevention of this vector-borne disease. RECENT FINDINGS:
We identified 11 JE cases in travelers that were published in peer-reviewed
literature since 2009. JE incidence in endemic countries appears to be declining
but the number of JE cases reported to the World Health Organization (WHO) varied
from estimates derived from other published reports based on serosurveys or
sentinel surveillance. Current JE vaccines appear to be safe and are not
associated with delayed hypersensitivity in contrast to the older mouse brain
vaccine. Given differences between WHO-reported cases and local surveillance
data, future research on true incidence is needed. Regular assessment will inform
JE risk in travelers. National and international guidelines on JE vaccination
varied; we suggest areas for improvement.
PMID- 29959549
TI - Synthesis and biological evaluation of a new series of ortho-carboranyl
biphenyloxime derivatives.
AB - (Z,Z')-1,1'-(4-ortho-Caboranyldimethyl)-bis(2-methoxyphenylethan-1-oxime)
intermediate 3 was synthesized by a three-step reaction with a final treatment
with base to give a new series of ortho-carboranyl biphenyloxime derivatives (4
8). Compounds 7 and 8 showed high solubility and the in vitro study results
revealed high levels of accumulation in HeLa cells with higher cytotoxicity and
boron uptake compared to L-boronphenylalanine.
PMID- 29959550
TI - In vitro antioxidant properties of the biflavonoid agathisflavone.
AB - PURPOSE: Free radicals are considered as the causative agents of a variety of
acute and chronic pathologies. Natural antioxidants have drawn attention of the
researchers in recent years for their ability to scavenge free radicals with
minimal or even no side effects. This study evaluates the antioxidant capacity of
agathisflavone, a naturally occurring biflavonoid by a number of in vitro
methods. METHODS: Agathisflavone was subjected to DPPH, ABTS, OH and NO radical
scavenging assay, reducing potential and inhibition of lipid peroxidation (TBARS)
test using trolox as a standard. RESULTS: Agathisflavone showed concentration
dependent antioxidant activity against all types of free radicals used in this
study. The antioxidant capacity, reducing potential and inhibition of lipid
peroxidation showed by agathisflavone were comparable to that of trolox.
CONCLUSION: Agathisflavone exhibited antioxidant capacity, which suggests
considering this biflavonoid for the use in the prevention and/or treatment of
diseases precipitated by oxidative stress.
PMID- 29959551
TI - Quantitative Comparison of Korotkoff Sound Waveform Characteristics: Effects of
Static Cuff Pressures and Stethoscope Positions.
AB - The underlying principles of Korotkoff sound (KorS) during blood pressure
measurement and its waveform characteristic changes with cuff pressure and
stethoscope position have not been fully understood. This study aimed to quantify
the effects of cuff pressure and stethoscope position on the measured KorS
waveform characteristics. Thirty healthy subjects were recruited in this study.
Four stethoscopes were placed on the circumferential direction around the arm
(m1, m2, m3 and m4; m1 was above the artery, and equal distance between each
other), and then sequentially at three different longitudinal positions ('upper',
'middle' and 'low' part under the cuff). At each longitudinal position, three
levels of static cuff pressure (high: SBP + 10 mmHg, low: DBP-10 mmHg, and
medium: DBP + (SBP-DBP)/3) were applied during the recording of KorS waveform.
The averaged KorS waveform was firstly computed by using an interpolation method,
separately for measurements from different stethoscope locations and cuff
pressures. Two quantitative indices were derived to characterize the recorded
KorS waveform: intensity amplitude and high-level duration of KorS waveform. Post
hoc pairwise comparisons after analysis of variance were used to compare the
waveform characteristic differences between different stethoscope locations and
between cuff pressures. Variance analysis demonstrated that the effects of
stethoscope circumferential and longitudinal positions and cuff pressure on the
two KorS waveform indices were significant (all p < 0.001). In detail, KorS
waveform recorded at cuff pressure PMEDIUM had larger intensity amplitude and
shorter high-level duration than those recorded at cuff pressure PHIGH or PLOW.
In most conditions, the stethoscope above the artery (m1) produced the largest
RMS intensity amplitude and shortest high-level duration, while the stethoscope
at the opposite location of m1 generated the smallest RMS intensity amplitude and
longest high-level duration. In terms of the effect of longitudinal position, the
stethoscopes below the middle of the cuff always produced KorS recordings with
larger intensity amplitude and shorter high-level duration. This study has
quantified and provided scientific evidence that cuff pressure, stethoscope
longitudinal and circumferential positions are important factors influencing KorS
waveform characteristics.
PMID- 29959552
TI - Answer to the Letter to the Editor of Manu N. Capoor et al. concerning "Low
virulence bacterial infections in cervical intervertebral discs: a prospective
case series" by Chen Y, Wang X, Zhang X, et al. (Eur Spine J; 2018: doi:
10.1007/s00586-018-5582-4).
PMID- 29959553
TI - The bridge crane technique for the treatment of the severe thoracic ossification
of the ligamentum flavum with myelopathy.
AB - PURPOSE: This study aims to investigate the clinical effect and complications of
a novel technique named bridge crane for the treatment of the severe thoracic
ossification of the ligamentum flavum (TOLF) with myelopathy. METHOD: A patient
diagnosed as TOLF (T9-T11) was treated with the bridge crane technique and the
outcomes were reported. The main surgical procedures include installation of
pedicle screws, rods and transverse connectors; preparation of stay prolene
sutures passing through the laminae-OLF complex (LOC); en bloc isolation of the
LOC; tightening of the sutures to achieve posterior suspension of the LOC; and
fixation of the LOC to the transverse connectors. The modified Japanese
Orthopaedic Association (mJOA) scale was studied. The pre- and postoperative
radiological parameters and surgical complications were also investigated.
RESULTS: Postoperative CT and MRI showed a sufficient decompression of spinal
cord by the technique of bridge crane. The ratio of spinal canal encroachment
improved significantly. At the final follow-up assessment, no specific
complications were identified. Imaging information suggested that the bone graft
was fused and the "bridge" was in good position. The mJOA score was 9 with a
recovery rate of 75% at the final follow-up. CONCLUSIONS: The technique of bridge
crane is feasible and may be relatively safe and effective for the treatment of
severe TOLF with myelopathy. However, further studies with large-scale cases and
control groups are required to reveal the generalizability and safety of the
bridge crane technique in the future. These slides can be retrieved under
Electronic Supplementary Material.
PMID- 29959554
TI - Proximal junctional kyphosis in thoracic adolescent idiopathic scoliosis: risk
factors and compensatory mechanisms in a multicenter national cohort.
AB - INTRODUCTION: Proximal junctional kyphosis (PJK) is a frequent complication, up
to 46%, in adolescent idiopathic scoliosis surgical treatment (AIS). Several risk
factors have been evoked but remain controversial. The purpose of this study was
to analyze the incidence of PJK in a multicenter cohort of AIS patient and to
determine risk factor for PJK. MATERIALS AND METHODS: Lenke I and II AIS patients
operated between 2011 and 2015 (minimum of 2-years follow-up) were included. On
fullspine X-rays, coronal and sagittal radiographic parameters were measured
preoperatively, postoperatively and at final follow-up. Occurrence of
radiological PJK corresponding to a 10 degrees increase in the sagittal Cobb
angle, measured between the upper instrumented vertebra (UIV) and UIV + 2,
between postoperative and 2-years follow-up X-rays, was reported. RESULTS: Among
the 365 patients included, 15.6% (n = 57) developed a PJK and only 10 patients
required a revision surgery. Preoperatively, PJK patients had significantly
larger pelvic incidence (57 degrees +/- 13 degrees vs. 51 degrees +/- 12
degrees ), larger lumbar lordosis (LL) (63 degrees +/- 12 degrees vs. 57
degrees +/- 11 degrees ) and bigger C7 slope. Postoperatively (3 months), in the
non-PJK group, thoracic kyphosis (TK) was increased and LL was not significantly
different. However, postoperatively, in the PJK group, no significant change was
observed in TK, whereas C7 slope decreased and LL significantly increased. There
was also a postoperative change in inflection point which was located at a more
proximal level in the PJK group. Between postoperative time and final follow-up,
TK and LL significantly increased in the PJK group. CONCLUSION: PJK is a frequent
complication in thoracic AIS, occurring 16%, but remains often asymptomatic (less
than 3% of revisions in the entire cohort). An interesting finding is that
patients with high pelvic incidence and consequently large LL and TK were more at
risk of PJK. As demonstrated in ASD, one of the causes of PJK might be
postoperative posterior imbalance that can be due to increased LL, insufficient
TK or inflection point shift during surgery. These slides can be retrieved under
Electronic Supplementary Material.
PMID- 29959556
TI - Mitochondrial DNA control region diversity in a population from Parana state
increasing the Brazilian forensic database.
AB - The entire mitochondrial DNA (mtDNA) control region (nucleotide position 16024
576) sequences were obtained through Sanger sequencing method for 122 individuals
from Parana state, South of Brazil. We observed a total of 108 different
haplotypes of which 97 were unique and 11 were shared by more than one
individual. The haplogroups were classified according to the updated mtDNA
phylogeny, by EMMA (estimating mitochondrial haplogroups using a maximum
likelihood approach). Our results revealed the predominance of Amerindian
haplogroups with a frequency of 49.2% of the population sample, followed by
European lineages with 38.5% and 12.3% of African lineages. Parana population
sample set presented a high haplotype diversity (0.9976) and the random match
probability was 0.0106. The phylogenetical findings and the diversity indices
confirm the high genetic heterogeneity of this population and suggest a high
informativeness of mtDNA analyses in forensic cases. The population data will
contribute to increase the Brazilian mtDNA database for forensic purposes and it
is available through EMPOP (European DNA Profiling Group mitochondrial DNA
population database) under the accession number EMP00714.
PMID- 29959557
TI - Mass poisoning with NPS: 2C-E and Bromo-DragonFly.
AB - BACKGROUND: Reports of intoxications with new psychoactive substances (NPS)
mostly involve young people, as they are the main consumers of these types of
drugs. This report centers on a case that was unusual due to it being a mass
poisoning event involving middle-aged individuals who had consumed a combination
of the two different new psychoactive drugs 2,5-dimethoxy-4-ethylphenethylamine
(2C-E) and 1-(8-bromofuro[2,3-f][1]benzofuran-4-yl)-2-propanamine (Bromo
DragonFly, BDF). CASE HISTORY: The mass poisoning of 29 individuals (24-56 years
old) resulted in their admission to six different hospitals with severe symptoms
of intoxication. All symptoms manifested after consumption of an unknown drug
formulation around lunchtime during an esoteric weekend seminar. INVESTIGATION:
Urine (n = 11) and blood samples (n = 29), collected from the 29 individuals for
police investigation, were analyzed with immunochemical techniques, GC/MS and LC
MS/MS. 2C-E was confirmed in seven urine samples, but not in blood. BDF was
confirmed in all urine samples, and in 17 blood samples. The blood samples
exhibited BDF concentrations between ca. 0.6 and ca. 2.0 MUg/L, while urine
concentrations of BDF ranged from ca. 1.6 to 35 MUg/L. The concentration of 2C-E
in urine was found to be between ca. 1.5 and 183 MUg/L. All patients made a
complete recovery, although some had required mechanical ventilation. CONCLUSION:
The investigation and the presentation of this case illustrates not only mass
intoxication with 2C-E and BDF, with corresponding blood and urine
concentrations, but also the necessity of collecting urine samples in cases where
NPS-consumption is suspected, in order to improve the chances of analytical
detection.
PMID- 29959555
TI - Long-term evolution of patient-reported outcome measures in spinocerebellar
ataxias.
AB - INTRODUCTION: To study the long-term evolution of patient-reported outcome
measures (PROMs) in the most common spinocerebellar ataxias (SCAs), we analyzed 8
years follow-up data of the EUROSCA Natural History Study, a cohort study of 526
patients with SCA1, SCA2, SCA3 and SCA6. METHODS: To assess the functional
capacity in daily living, we used the functional assessment (part IV) of the
Unified Huntington's Disease Rating Scale (UHDRS-IV), for health-related quality
of life the visual analogue scale of the EuroQol Five Dimensions Questionnaire
(EQ-5D VAS), and for depressive symptoms the Patient Health Questionnaire (PHQ
9). Severity of ataxia was assessed using the Scale for the Assessment and Rating
of Ataxia (SARA) and neurological symptoms other than ataxia with the Inventory
of Non-Ataxia Signs (INAS). RESULTS: UHDRS-IV [SCA1: - 1.35 (0.12); SCA2: - 1.15
(0.11); SCA3: - 1.16 (0.11); SCA6: - 0.99 (0.12)] and EQ-5D [SCA1: - 2.88 (0.72);
SCA2: - 1.97 (0.49); SCA3: - 2.06 (0.55); SCA6: - 1.03 (0.57)] decreased
linearly, whereas PHQ-9 increased [SCA1: 0.15 (0.04); SCA2: 0.09 (0.03); SCA3:
0.06 (0.04); SCA6: 0.07 (0.04)] during the observational period. Standard
response means (SRMs) of UHDRS-IV (0.473-0.707) and EQ-5D VAS (0.053-0.184) were
lower than that of SARA (0.404-0.979). In SCA1, higher SARA scores [- 0.0288
(0.01), p = 0.0251], longer repeat expansions [- 0.0622 (0.02), p = 0.0002] and
the presence of cognitive impairment at baseline [- 0.5381 (0.25), p = 0.0365]
were associated with faster UHDRS-IV decline. In SCA3, higher INAS counts were
associated with a faster UHDRS-IV decline [- 0.05 (0.02), p = 0.0212]. In SCA1,
PHQ-9 progression was faster in patients with cognitive impairment [0.14 (0.07);
p = 0.0396]. CONCLUSIONS: In the common SCAs, PROMs give complementary
information to the information provided by neurological scales. This underlines
the importance of PROMs as additional outcome measures in future interventional
trials.
PMID- 29959558
TI - Identification of potential markers of fatal hypothermia by a body temperature
dependent gene expression assay.
AB - Diagnosis of fatal hypothermia is considered to be difficult in forensic practice
and even if findings due to cold exposure are evident, cold exposure is not
necessarily a direct cause of death. Identification of useful molecular markers
for the diagnosis of fatal hypothermia has not been successful. In this study, to
identify novel molecular markers that inform the diagnosis of fatal hypothermia,
we focused on skeletal muscle, which plays a role in cold-induced thermogenesis
in mammals. We made rat models of mild, moderate, and severe hypothermia and
performed body temperature-dependent gene expression analysis in the iliopsoas
muscle using next-generation sequencing (NGS). NGS showed that after severe
hypothermia, the expression levels of 91 mRNAs were more than double those in
mild and moderate hypothermia and control animals. Gene ontology (GO) analysis
indicated that these mRNAs are involved in a number of biological processes,
including response to stress and lipids, and cellular response to hypoxia. The
expression of four genes [connective tissue growth factor (Ctgf), JunB proto
oncogene, AP-1 transcription factor subunit (Junb), nuclear receptor subfamily 4,
group A, member 1 (Nr4a1), and Syndecan 4 (Sdc4)] and the level of one protein
(CTGF) were induced only by severe hypothermia. These genes and protein are
involved in muscle regeneration, tissue repair, and lipid metabolism. These
results indicate that heat production to maintain body temperature in a process
leading to fatal hypothermia might be performed by the iliopsoas muscle, and that
Ctgf, Junb, Nr4a1, and Sdc4 genes are potential diagnostic markers for fatal
hypothermia.
PMID- 29959559
TI - Oxidative stress induced by Porphyromonas gingivalis lysate and nicotine in human
periodontal ligament fibroblasts.
AB - Porphyromonas gingivalis (P. gingivalis) and nicotine have been implicated as a
major pathogen in the development and progression of periodontitis. One of the
possible mechanism is via the oxidative stress of human periodontal ligament
fibroblasts (PDLF) which lead to the damage of cell viability and function. This
study aimed to investigate oxidative stress (OS) levels in the cultured media of
human PDLF under the induction of P. gingivalis lysate and nicotine. Primary PDLF
was cultured in growth media under P. gingivalis or/and nicotine treatment in
different concentrations for 2 and 24 h. Following incubation, oxidative stress
molecules malondialdehyde (MDA) and oxidized guanine species (Ox-GS) from the
cell cultured supernatant were determined by spectrophotometric assay and ELISA,
respectively. DCFDA and superoxide assays were performed to verify the production
of ROS and intracellular superoxide radical under various stimuli. As a result,
at both 2 and 24 h, Ox-GS and MDA levels in the medium of cells treated with
different concentrations of P. gingivalis lysate and nicotine, either separately
or in combination, were significantly different from the negative controls in a
dose- and time-dependent manner. Interestingly, except MDA levels in P.
gingivalis lysate at 20 ug/ml, MDA levels in all other tested conditions were
found as same as one in the positive controls after 24 h. ROS and superoxide
production were enhanced under P. gingivalis and/or nicotine stimulation.
Therefore, OS biomarkers were generated by PDLF upon treatment with periodontal
pathogens and nicotine which could elucidate a potential local mechanism of
periodontal disease etiology via superoxide mediation.
PMID- 29959560
TI - miR-153 inhibits the migration and the tube formation of endothelial cells by
blocking the paracrine of angiopoietin 1 in breast cancer cells.
AB - The sprouting of endothelial cells is the first step of tumor angiogenesis. Our
previous study suggests that miR-153 suppresses breast tumor angiogenesis
partially through targeting hypoxia-induced factor (HIF1alpha). In this study, we
demonstrated that miR-153 also suppresses the migration and the tube formation of
endothelial cells through directly targeting angiopoietin 1 (ANG1) in breast
cancer cells. There was a negative correlation between miR-153 and ANG1 levels in
breast cancer. miR-153 blocked the expression and secretion of ANG1 in breast
cancer cells through binding to ANG1 mRNA. Conditioned medium from the breast
cancer cell, MCF7, treated with miR-153 had no effect on the proliferation of
HUVECs, but significantly inhibited the migration and tube formation of HUVECs,
which could be rescued by overexpression of ANG1. In addition, miR-153 also
directly inhibited the proliferation and migration of MCF7 through downregulation
of ANG1. These findings suggest that miR-153 suppresses the activity of tumor
cells and the migration and tube formation of endothelial cells by silencing
ANG1.
PMID- 29959561
TI - P53/PUMA are potential targets that mediate the protection of brain-derived
neurotrophic factor (BDNF)/TrkB from etoposide-induced cell death in
neuroblastoma (NB).
AB - The over-expressions of brain-derived neurotrophic factor (BDNF) and its tyrosine
kinase receptor TrkB have been reported to induce chemo-resistance in
neuroblastoma (NB) cells. In this study, we investigated the roles of P53 and
BCL2 family members in the protection of BDNF/TrkB from etoposide-induced NB cell
death. TB3 and TB8, two tetracycline (TET)-regulated TrkB-expressing NB cell
lines, were utilized. The expressions of P53 and BCL2 family members were
detected by Western blot or RT-PCR. Transfection of siRNAs was used to knockdown
P53 or PUMA. Activated lentiviral was used to over-express PUMA. Cell survival
was performed by MTS assay, and the percentage of cell confluence was measured by
IncuCyte ZOOM. Our results showed that etoposide treatment induced significant
and time-dependent increase of P53, which could be blocked by pre-treatment with
BDNF, and knockdown P53 by transfecting siRNA attenuated etoposide-induced TrkB
expressing NB cell death. PUMA was the most significantly changed BCL2 family
member after treatment with etoposide, and pre-treatment with BDNF blocked the
increased expression of PUMA. Transfection with siRNA inhibited etoposide-induced
increased expression of PUMA, and attenuated etoposide-induced NB cell death. We
also found that over-expression of PUMA by infection of activated lentiviral
induced TrkB-expressing NB cell death in the absence of etoposide, and treatment
of BDNF protected NB cells from PUMA-induced cell death. Our results suggested
that P53 and PUMA may be potential targets that mediated the protection of
BDNF/TrkB from etoposide-induced NB cell death.
PMID- 29959562
TI - Social behaviour and social cognition in high-functioning adolescents with autism
spectrum disorder (ASD): two sides of the same coin?
AB - Of the triad of symptoms found in autism spectrum disorder (ASD), that is, social
impairments, communication difficulties and repetitive interests and behaviour,
the social impairments are the most stable and common throughout the lifespan.
They typically manifest themselves in abnormalities as reciprocal interactions
and difficulties in the expression and recognition of emotions. Although peer
interactions become especially important during adolescence, little is known
about the mentalizing abilities of high-functioning adolescents with ASD. Here,
we compared the mentalizing skills and emotion recognition abilities of 21 high
functioning adolescents with ASD and 21 matched controls. All adolescents had
estimated above-average verbal intelligence levels. Spontaneous social abilities
and task-related social abilities were measured using questionnaires, tasks and
the Autism Diagnostic Observation Schedule. Results confirm social impairment in
daily life situations in adolescents with ASD, but were not found on experimental
tasks of social cognition. The use of more explicit cognitive or verbally
mediating reasoning techniques and a lesser tendency of high-functioning
adolescents with ASD to search for and use social information in natural
environments are further discussed.
PMID- 29959563
TI - Radiotherapy combined with zoledronate can reduce skeletal-related events in
renal cell carcinoma patients with bone metastasis.
AB - BACKGROUND: Skeletal-related events (SRE) are common in patients with renal cell
carcinoma (RCC) that includes bone metastasis. The purpose of this study was to
clarify the effectiveness of zoledronate with and without sunitinib, combined
with radiotherapy, for the treatment of bone metastasis from RCC. METHODS: We
retrospectively analyzed 62 RCC patients with bone metastasis, who had been
treated with radiotherapy at our institution. We divided the study cohort into
two groups: patients treated with radiotherapy alone (RT; n = 27) and those
treated with radiotherapy combined with zoledronate (RT + Z; n = 35). We
investigated the overall survival and post-irradiation (PI)-SRE-free rate for
each group, as well as the effect of sunitinib in the RT + Z treatment group. In
addition, we determined treatment effectiveness by imaging assessments and
relative response rates. RESULTS: There was no significant difference in the
survival rates between the RT and RT + Z treatment groups (p = 0.11). However,
the PI-SRE-free rate in the RT + Z group was significantly higher than that in
the RT group (p = 0.02). The PI-SRE-free rate was significantly higher in
patients who were treated with sunitinib after radiotherapy than in those who
were treated without sunitinib (p = 0.03). However, there was no significant
difference in the relative response rates, as assessed by imaging, in each group.
CONCLUSION: Radiotherapy combined with zoledronate is an effective treatment for
RCC with bone metastasis to prevent PI-SRE. Sunitinib may reduce PI-SRE if used
after radiotherapy and combined with zoledronate.
PMID- 29959564
TI - A novel three-dimensional-printed paranasal sinus-skull base anatomical model.
AB - PURPOSE: A novel precision three-dimensional (3D)-printed paranasal sinus-skull
base anatomical model was generated with a commercial grade desktop 3D printer. A
specific page-turning pattern was employed in this model, to display the internal
spatial structure of the paranasal sinus. METHODS: The CT image data of paranasal
sinus were imported into the Mimics software to construct a 3D digital paranasal
sinus-skull base model. Then, the model was sliced in the coronal position and
loaded into the 3D printer to print each slice of the paranasal sinus-skull base
model at a ratio of 1:1 in size. Based on CT image data, nine senior doctors
assessed the simulation and accuracy of the anatomical structure features of the
paranasal sinus-skull base, and the advantages and educational value of the 3D
printing model using a seven-point Likert scale. RESULTS: A life-like 3D
paranasal sinus-skull base structural model was successfully printed, with its
internal spatial details clearly displayed. Nine senior doctors all thought that
the profile of the printed anatomical structure was similar to that displayed by
CT scan; however, the model provided more 3D spatial visual information. In
addition, the model was considered to be of great value in the anatomy teaching
and complicated surgery of the paranasal sinus-skull base, which had a material
cost of only 3 dollars. CONCLUSIONS: The 3D printed paranasal sinus-skull base
model has 3D visual functions, which provides a novel tool for anatomical studies
on paranasal sinus, resident training, pre-surgical education and surgical
planning.
PMID- 29959566
TI - Organ preservation vs primary surgery in the management of T3 laryngeal and
hypopharyngeal cancers.
AB - OBJECTIVE: The main objective is to compare the oncologic outcomes of patients
with T3 laryngeal cancers who underwent total laryngectomy or organ preservation
protocol (OPP) as the initial plan of management. MATERIALS AND METHODS: This is
a retrospective study on 120 patients treated for T3 laryngeal and hypopharyngeal
cancers. Patients with functional larynx underwent OPP and dysfunctional larynx
underwent upfront laryngectomy. Median follow-up of the patients was 4.6 years.
RESULTS: There was a significant difference in 3 year disease-free survival (DFS)
between upfront laryngectomy and OPP (73.2 vs. 55.7%; P = 0.028) group but not in
3 year overall survival (73.2 vs. 68.7%, P = 0.8). The rate laryngeal
preservation was 65% in CCRT and 44% in only radiotherapy group. At 3 years, the
laryngectomy-free survival was 57.2% and the laryngo-esophageal dysfunction-free
survival (LEDS) was 53.0%. CONCLUSION: T3 laryngeal cancers treated with upfront
laryngectomy have an improved DFS when compared to those treated with non
surgical modalities. Primary surgery should be offered as an option for selected
patients especially when CCRT is not feasible.
PMID- 29959567
TI - Quality assurance in head and neck surgery: special considerations to catch up.
AB - PURPOSE: Quality assurance is much more difficult to achieve in surgical oncology
than in medical oncology and radiotherapy where doses are standardized and
toxicities are well-classified. To better define what is required in surgery, we
analyzed recent articles addressing the point in head and neck surgery. RESULTS:
The surgical report should match with the pathological description of the
resected specimen with accurate delineation of the margins, number and level(s)
of lymph nodes (capsular rupture if any). Complications (minor and major) should
be standardized and meticulously recorded; as well as comorbidities and patient
status. The acuity of the procedure should be defined by metrics collected in
check-lists. Age > 60 years, male gender, tumor site and T4 stage, neck
dissection(s), flap reconstruction, alcohol and tobacco consumption, are
acknowledged risk factors for more complications and longer hospital stay (or
readmission). NEEDS: Randomized controlled trials should be designed adopting the
consolidated standards of reporting trials (CONSORT). Training young head and
neck surgeons should encompass formation in designing, conducting and
interpreting clinical trials.
PMID- 29959565
TI - Antibiofilm effects of amoxicillin-clavulanic acid and levofloxacin in patients
with chronic rhinosinusitis with nasal polyposis.
AB - PURPOSE: Microbial biofilms have been implicated in the pathogenesis of chronic
rhinosinusitis with nasal polyposis (CRSwNP). The aim of our study was to
evaluate in vitro effects of amoxicillin-clavulanic acid and levofloxacin on
biofilm formation by bacterial species isolated from sinus tissue in patients
with CRSwNP. METHODS: The sinus mucosal specimens were harvested from the upper
parts and roof of ethmoid cavity of 48 patients with CRSwNP. Each sample was
washed thoroughly in three separate beakers of sterile saline to remove any
planktonic bacteria and further subjected to microbiology analysis. The biofilm
forming capacity of isolated strains was detected by microtiter-plate method and
the effects of subinhibitory (1/2* to 1/16* MIC) and suprainhibitory
concentrations (4, 8, 16, 32, and 64 ug/ml) of amoxicillin-clavulanic acid and
levofloxacin on biofilm production were investigated. RESULTS: Bacterial strains
were isolated in 42 (87.5%) patients: one microorganism in 80.9% and two
microorganisms in 19.1% of patients. The most prevalent bacteria in CRSwNP
biofilms were Staphylococcus epidermidis (34%) and S. aureus (28%) followed by S.
haemolyticus (12%), Pseudomonas aeruginosa (8%), Moraxella catarrhalis (6%),
Streptococcus pneumoniae (6%), and other staphylococci (6%). Subinhibitory
concentrations of amoxicillin-clavulanic acid and levofloxacin significantly
reduced biofilm formation (p < 0.01 and p < 0.05, respectively), with better
efficacy of amoxicillin-clavulanic acid (1/2-1/8* MIC) on staphylococci and
levofloxacin (1/2- 1/4* MIC) on M. catarrhalis and P. aeruginosa biofilm
formation. Suprainhibitory concentrations of both tested antibiotics (4-64 ug/ml)
significantly eradicated mature biofilms of staphylococci (p < 0.01). The effect
of levofloxacin on eradication of staphylococcal biofilms was more noticeable,
compared to the effect of amoxicillin-clavulanic acid (p < 0.01). Suprainhibitory
concentrations of both tested antibiotics had no effect on eradication of
previously formed M. catarrhalis and P. aeruginosa biofilms (p > 0.05).
CONCLUSIONS: The amoxicillin-clavulanic acid and levofloxacin are shown to be
potent antibiofilm agents in patients with CRSwNP. The effects of tested
compounds depend on bacterial species and the volume of formed biofilm.
PMID- 29959568
TI - Safety and effectiveness of eculizumab for adult patients with atypical hemolytic
uremic syndrome in Japan: interim analysis of post-marketing surveillance.
AB - BACKGROUND: Eculizumab has been available for the treatment of atypical hemolytic
uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of
eculizumab in adult aHUS patients in the real-life setting, we performed interim
analysis of a post-marketing surveillance mandated by Japanese regulations.
METHODS: This study enrolled any patient who was diagnosed with TMA excluding
Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura
based on Japanese clinical guide published in 2013 as inclusion criteria and
treated with eculizumab. Although the term aHUS was redefined to denote only
complement-mediated HUS in the guide revised in 2016, the patients with TMA
caused by other causes (secondary TMA) were included. Patient outcomes and safety
were evaluated at 6 months, 12 months, and annually thereafter. RESULTS: Thirty
three patients with aHUS and 27 patients with secondary TMA were enrolled. Median
treatment duration of aHUS was 24weeks. Complement genes variants were detected
in 11 of 18 patients with aHUS (61.1%). Among the 29 aHUS patients with available
baseline data, platelet count (PLT), lactic dehydrogenase and serum creatinine
(SCr) improved within 1-month after eculizumab initiation. TMA event-free status,
complete TMA response, PLT normalization, and SCr decrease were achieved in 67.9%
(19/28), 27.8% (5/18), 56.5% (13/23), and 57.1% (16/28) of patients,
respectively. Thirty-three and 11 adverse reactions were observed in patients
with aHUS (13/33 patients) and secondary TMA (6/27 patients), respectively.
CONCLUSIONS: This interim analysis confirmed the acceptable safety profile and
effectiveness of eculizumab for Japanese adult aHUS patients in real-world
settings.
PMID- 29959569
TI - Disruption of MEK/ERK/c-Myc signaling radiosensitizes prostate cancer cells in
vitro and in vivo.
AB - PURPOSE: Prostate cancer (PCa) cell radioresistance causes the failure of
radiation therapy (RT) in localized or locally advanced disease. The aberrant
accumulation of c-Myc oncoprotein, known to promote PCa onset and progression,
may be due to the control of gene transcription and/or MEK/ERK-regulated protein
stabilization. Here, we investigated the role of MEK/ERK signaling in PCa.
METHODS: LnCAP, 22Rv1, DU145, and PC3 PCa cell lines were used in in vitro and in
vivo experiments. U0126, trametinib MEK/ERK inhibitors, and c-Myc shRNAs were
used. Radiation was delivered using an x-6 MV photon linear accelerator. U0126 in
vivo activity alone or in combination with irradiation was determined in murine
xenografts. RESULTS: Inhibition of MEK/ERK signaling down-regulated c-Myc protein
in PCa cell lines to varying extents by affecting expression of RNA and protein,
which in turn determined radiosensitization in in vitro and in vivo xenograft
models of PCa cells. The crucial role played by c-Myc in the MEK/ERK pathways was
demonstrated in 22Rv1 cells by the silencing of c-Myc by means of short hairpin
mRNA, which yielded effects resembling the targeting of MEK/ERK signaling. The
clinically approved compound trametinib used in vitro yielded the same effects as
U0126 on growth and C-Myc expression. Notably, U0126 and trametinib induced a
drastic down-regulation of BMX, which is known to prevent apoptosis in cancer
cells. CONCLUSIONS: The results of our study suggest that signal transduction
based therapy can, by disrupting the MEK/ERK/c-Myc axis, reduce human PCa
radioresistance caused by increased c-Myc expression in vivo and in vitro and
restores apoptosis signals.
PMID- 29959570
TI - FOXM1 predicts disease progression in non-muscle invasive bladder cancer.
AB - PURPOSE: The proto-oncogene forkhead box M1 (FOXM1) is associated with poor
survival in many cancers. The impact of FOXM1 expression on progression-free
survival (PFS) of non-muscle invasive bladder cancer (NMIBC) has not yet been
investigated. The differential expression of FOXM1 between the different
molecular NMIBC subtypes has further been assessed. METHODS: Transcript levels of
FOXM1 and MKI67 were determined in 460 NMIBC patients (UROMOL cohort) by RNA-Seq
and validated in silico by the Chungbuk and Lund cohort (n = 277). FOXM1 and
MKI67 cutoffs were identified by the minimal p value method. Variables were
evaluated by multivariable Cox regression analyses in order to identify
independent predictors. RESULTS: FOXM1 is an independent predictor for PFS
superior to current histological, clinical and molecular staging methods.
Patients with high FOXM1 expression have a 6- to 8-fold higher risk of
progression in multivariable analysis (p < 0.03). Highest transcript levels were
found in the Class 2 and genomically unstable molecular NMIBC subtype (p < 0.03).
The proto-oncogene further positively correlated with tumor grade and stage.
NMIBCs with high FOXM1 expression showed a PFS advantage when treated with
intravesical BCG instillation. CONCLUSION: FOXM1 is a highly prognostic marker
for disease progression of NMIBC superior to current histological, clinical and
molecular staging methods and MKI67. It is mainly expressed in the Class 2 and
genomically unstable molecular bladder cancer subtypes. Its role in drug
resistance development makes FOXM1 valuable biomarker for NMIBC risk
stratification.
PMID- 29959571
TI - Effects of extreme changes in precipitation on the physiology of C4 grasses.
AB - Climatic patterns are expected to become more extreme, with changes in
precipitation characterized by heavier rainfall and prolonged dry periods. Yet,
most studies focus on persistent moderate changes in precipitation, limiting our
understanding of how ecosystems will function in the future. We examined the
effects of extreme changes in precipitation on leaf-level and ecosystem CO2 and
H2O exchange of three native C4 bunchgrasses (Andropogon gerardii, Panicum
virgatum, and Sorghastrum nutans) over 3 years. Grasses were grown in three
precipitation treatments: extreme dry, mean, and extreme wet based on historical
rainfall records. After 3 years, plants were 45% smaller in the extreme dry
treatment relative to the mean and extreme high treatment, which did not differ.
We also found that an extreme decrease in precipitation caused reductions of 55,
40, and 40% in leaf-level photosynthesis (Anet), stomatal conductance (gs), and
water use efficiency (WUE), respectively. Extreme increases in precipitation
inhibited leaf-level WUE, with a 44% reduction relative to the mean treatment. At
the ecosystem level, both an extreme increase and decrease in precipitation
reduced net CO2 and water fluxes relative to plants grown with mean levels of
precipitation. Net water fluxes (ET) were reduced by an average of 74% in the
extreme dry and extreme wet treatment relative to mean treatment; net carbon
fluxes followed a similar trend, with average reductions of 68% (NEE) and 100%
(Re). Unlike moderate climate change, extreme increases in precipitation may be
just as detrimental as extreme decreases in precipitation in shifting grassland
physiology.
PMID- 29959572
TI - Resource limitation alters effects of phenological shifts on inter-specific
competition.
AB - Phenological shifts can alter the relative arrival time of competing species in
natural communities, but predicting the consequences for species interactions and
community dynamics is a major challenge. Here we show that differences in
relative arrival time can lead to predictable priority effects that alter the
outcome of competitive interactions. By experimentally manipulating the relative
arrival time of two competing tadpole species across a resource gradient, we
found that delaying relative arrival of a species reduced the interaction
asymmetry between species and could even reverse competitive dominance. However,
the strength of these priority effects was contingent on the abundance of the
shared resource. Priority effects were generally weak when resources were
limited, but increased at higher resource levels. Importantly, this context
dependency could be explained by a shift in per capita interaction strength
driven by a shift in relative body sizes of competitors. These results shed new
light into the mechanisms that drive variation in priority effects and help
predict consequences of phenological shifts across different environments.
PMID- 29959573
TI - Breeding phenology, provisioning behaviour, and unusual patterns of life history
variation across an anthropogenic heterogeneous landscape.
AB - Understanding how resource use and life history variation influence a
population's response to modified, fragmented landscapes is a major challenge for
ecologists. We investigated the phenology, life history decisions and
provisioning behaviour of a generalist passerine-the great tit-across a heavily
managed woodland landscape. Contrary to most previous studies on this species,
reproductive investment and success were lower in deciduous than in coniferous
woodland fragments. This could not be explained by differences in provisioning
behaviour; instead population density was considerably higher in deciduous
woodlands, suggesting birds did not follow an ideal free distribution. Clutch
size declined with lay date amongst populations breeding in coniferous woodland
fragments, but these populations also displayed pronounced seasonal declines in
the proportion of fledglings produced per egg and fledgling mass. In contrast,
and against patterns observed in other similar study systems, clutch size did not
change with lay date in mixed-species deciduous woodland fragments. Furthermore,
the proportion of young fledged and fledgling condition remained stable
throughout the season, even though the quality of food provisioned to nestlings
increased over the season. Local recruitment was negligible, suggesting that
plasticity rather than natural selection played a key role in driving the
patterns observed. The unusual patterns we report are likely explained by the
fragmented nature of the landscape, and unreliable phenological cues in a mixed
species tree community coupled with low food availability. They contrast with
those reported from most other populations situated in continuous woodland,
demonstrating that caution is needed when generalising across different contexts
and ecosystems.
PMID- 29959574
TI - Using photography to explore psychological distress in patients with pancreatic
cancer and their caregivers: a qualitative study.
AB - PURPOSE: The quality of life (QOL) experiences of patients with pancreatic cancer
and their caregivers is poorly understood. Psychological distress is high, but
few studies examine the factors associated with psychological distress. The
purpose of this study is to gain a richer understanding of the factors associated
with psychological distress from patient and caregiver perspectives. METHODS:
Twenty participants (13 patients, 7 caregivers) completed group discussions on
the experiences of living with pancreatic cancer. Using photovoice methods,
participants took photographs and provided narratives depicting the distress they
experienced. Participant-produced photographs and group discussion transcripts
were analyzed to identify key themes using thematic analysis. RESULTS:
Commonalities between patient and caregiver sources of distress emerged despite
their distinct roles. Findings revealed four major areas of distress: diagnosis
of an unexpected advanced cancer, changes in roles and identity, management of
weight loss and gastrointestinal problems, and fear of the future. Participants
also discussed unique perspectives such as the stigma of pancreatic cancer and
caregiver guilt. CONCLUSIONS: Photovoice provides a unique insight into the lives
of patients with pancreatic cancer and their caregivers. Our findings contribute
to the gap in the current literature by providing a better understanding of the
factors surrounding pancreatic cancer distress. We also identify several clinical
recommendations to improve cancer care delivery and areas for future research.
PMID- 29959575
TI - The role of positive psychological changes in anxiety and depression of patients
with ovarian tumors and their partners: an observational study from the
population-based PROFILES registry.
AB - PURPOSE: It is unknown whether positive psychological changes (e.g., in life
perspective, self-perception, and social relationships) after being diagnosed
with ovarian cancer can reduce anxiety and depression in patients and their
partners. The first aim of the present study was to assess differences in anxiety
and depression between patients diagnosed with an ovarian tumor and their
partners. The second aim was to explore the mutual associations of patients' and
partners' posttraumatic growth and their anxiety and depressive symptoms.
METHODS: Participants included 130 Dutch couples of which one partner was
diagnosed with a borderline ovarian tumor or ovarian cancer between 2000 and
2010, as registered by the Netherlands Cancer Registry. In September 2011, a
questionnaire was sent including the Hospital Anxiety and Depression Scale
(anxiety and depression) and Cancer Survivors (Partners) Unmet Needs measure
(positive psychological changes). RESULTS: A one-way multivariate analysis of
variance showed that patients reported higher anxiety than partners, without
differences in depression. Contrasting to our expectations, an actor-partner
interdependence model revealed no mutual dyadic associations between positive
psychological changes and anxiety or depressive symptoms. CONCLUSIONS: Based on
these findings, positive psychological change seems to be an independent
construct unrelated to anxiety or depression in couples diagnosed with ovarian
tumors. Still, as ovarian tumor patients and partners suffer from high anxiety
and depression, further research investigating how these feelings can be reduced
in couples dealing with an ovarian tumor is necessary.
PMID- 29959576
TI - Accuracy of the World Health Organization Disability Assessment Schedule 2.0
(WHODAS 2.0) score as an objective assessment tool for predicting return-to-work
status after head and neck cancer in male survivors.
AB - PURPOSE: The objective of this nationwide study in Taiwan was to predict work
participation by using the World Health Organization Disability Assessment
Schedule 2.0 (WHODAS 2.0) score as an objective assessment tool. METHOD: Data
from between July 2012 and July 2017 regarding 1206 male head and neck cancer
(HNC) survivors with disability aged < 50 years were obtained from the Taiwan
Data Bank of Persons with Disability (TDPD). Demographic data and the WHODAS 2.0
scores were analyzed to compare employment statuses among HNC survivors. RESULTS:
The WHODAS 2.0 scores in all the domains were lower in unemployed than in
employed HNC survivors (p < 0.001). The receiver operating characteristic (ROC)
curve revealed that the summary WHODAS 2.0 score (area under curve > 0.8) was an
extremely accurate predictive tool. Binary logistic regression revealed that the
severity levels of impairment and standardized WHODAS 2.0 summary scores less
than the cutoff value (27.81) were predictors for the return-to-work (RTW) status
of HNC survivors with disability in the working age group. CONCLUSIONS: The
WHODAS 2.0 score is an objective quantitative assessment tool for evaluating the
RTW possibility among these patient groups.
PMID- 29959577
TI - Positive mental health among cancer survivors: overlap in psychological well
being, personal meaning, and posttraumatic growth.
AB - PURPOSE: Positive mental health involves theoretical constructs like
psychological well-being, personal meaning, and posttraumatic growth. This study
aims to provide empirical insight into possible overlap between these constructs
in cancer survivors. METHODS: Within the context of a randomized controlled
trial, 170 cancer survivors completed the patient-reported outcome measures
(PROMs) Ryff's Scales of Psychological Well-Being (SPWB), Personal Meaning
Profile (PMP), and Posttraumatic Growth Inventory (PTGI). Exploratory factor
analysis (EFA) on the subscales of these PROMs, as well as structural equation
modeling (SEM), was used to explore overlap in these three constructs. RESULTS:
The EFA resulted in a three-factor solution with an insufficient model fit. SEM
led to a model with a high estimated correlation (0.87) between SPWB and PMP and
lower estimated correlations with PTGI (respectively 0.38 and 0.47). Furthermore,
the estimated correlation between the subscales relation with God (PMP) and
spiritual change (PTGI) was high (0.92). This model had adequate fit indices
(chi2(93) = 144, p = .001, RMSEA = 0.059, CFI = 0.965, TLI = 0.955, SRMR =
0.061). CONCLUSIONS: The constructs psychological well-being and personal meaning
overlap to a large extent in cancer survivors. Posttraumatic growth can be seen
as a separate construct, as well as religiosity. These findings facilitate
researchers to select the appropriate PROM(s) when testing the effect of a
psychosocial intervention on positive mental health in cancer survivors.
RELEVANCE: An increasing number of psychosocial intervention trials for cancer
survivors use positive mental health outcomes. These constructs are often
multifaceted and overlapping. Knowledge of this overlap is important in designing
trials, in order to avoid the pitfalls of multiple testing and finding
artificially strengthened associations. NETHERLANDS TRIAL REGISTER: NTR3571.
PMID- 29959578
TI - Aggregation Behavior of pHLIP in Aqueous Solution at Low Concentrations: A
Fluorescence Study.
AB - pH (low) insertion peptide (pHLIP) is a 36-residue peptide derived from the third
transmembrane helix of the membrane protein bacteriorhodopsin. The hydrophobicity
of this peptide makes it prone to aggregation even at low concentrations, but
this has not been studied in detail. In this work, we characterized monomeric and
aggregated forms of pHLIP in aqueous solution (pH 8) at low concentrations (~MUM)
using fluorescence-based approaches, complemented by circular dichroism (CD)
spectroscopy. We show here that monomeric and aggregated pHLIP display
differential red edge excitation shift (REES) and CD spectra. These spectroscopic
features allowed us to show that pHLIP aggregates even at low concentrations. A
detailed knowledge of the aggregation behavior of pHLIP under these conditions
will be useful for monitoring and quantifying its interaction with membranes.
PMID- 29959579
TI - Comparative DFT Computational Studies with Experimental Investigations for Novel
Synthesized Fluorescent Pyrazoline Derivatives.
AB - A novel series of pyrazoline derivatives were synthesized and their spectral
properties were characterized via FT-IR, 1H, and 13C NMR. The electronic
transitions and fluorescence properties were tracked via UV-Vis and emission
spectrometry. The density functional theory (DFT) calculations have been also
computed to get spot onto the geometry, electronic transitions and spectroscopic
properties theoretically that has been compared with the encountered experimental
ones. Moreover, the dipole moment, optimized energy, HOMO - LUMO energies and
band gaps were calculated for novel candidates pyrazoline derivatives with highly
fluorescence quantum yield.
PMID- 29959580
TI - Boosting systemic pressure with phenylephrine: arterial or venous modulation?
PMID- 29959581
TI - Organochlorine contaminants in the Vistula Lagoon sedimentation zone as possible
source of lagoon recontamination.
AB - The presented results include decade of monitoring of the Vistula Lagoon waters
and have been supplemented by the determination of chlorinated compounds, as well
as on concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans
(PCDD/Fs) in the sedimentation zone. Monitoring of river waters entering the
Polish part of the lagoon and the lagoon waters confirmed the presence of plant
protection chemical; the largest contributors has lindane (34%) and DDTtotal
(21%); the same as for sediments were dominate lindane (19%) and DDTtotal (14%)
within pp-DDT isomer dominate (13%). In the lagoon water, PCDD/Fs were determined
within a range of 1.5-5.6 ng dm-3, leading to average toxicity of 0.18 +/- 0.13
ng TEQ.dm-3. In sediments, their concentrations fell within a range of 22.7-405.7
ng kg-1 dw and the average toxicity of the lagoon sediments was set at 5.00 +/-
1.98 ng TEQ.kg-1 dw. Both in water and sediments, the greatest share among
PCDD/Fs has octa-chlorodibenzodioxin. Due to the hydromorphological conditions of
the lagoon, the waters are mixed to the bottom causing the surface layer of
sediment to become remobilized-this is suggested as the key factor when it comes
to water recontamination and increased access of POPs to marine organisms.
PMID- 29959582
TI - Bladder Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer.
AB - PURPOSE OF REVIEW: Here, we will review and summarize the current status and
emerging data supporting the use of trimodality therapy as an alternative to
cystectomy for patients with muscle-invasive bladder cancer. RECENT FINDINGS:
There are no randomized-controlled data comparing radical cystectomy with bladder
preserving trimodality therapy available for comparison. However, observational
data suggests acceptable bladder preservation and functional outcomes in patients
receiving bladder preserving trimodality therapy as well as similar oncologic
outcomes in select patients compared to radical cystectomy. Future trials are
focusing on new techniques and novel therapeutics in patients with bladder
cancer. Bladder preserving trimodality therapy results in satisfactory quality of
life and comparable disease outcomes for select patients with muscle-invasive
urothelial carcinoma of the bladder compared to cystectomy.
PMID- 29959583
TI - Probing the robustness of the charge-charge transfer-dipolar polarization model
and infrared intensities.
AB - The robustness of the QTAIM charge-charge transfer-dipolar polarization
parameters for the CH, CF, and CCl stretching and bending distortions of the
fluoro- and chloromethanes was determined comparing results calculated at three
quantum levels, MP2/6-311G++(3d,3p), QCISD/cc-pVTZ, and QCISD/aug-cc-pVTZ. The
correlation coefficients between the MP2/6-311G++G(d,p) and QCISD/cc-pVTZ results
with those of QCISD/aug-cc-pVTZ intensities are excellent, 0.934 and 0.988,
respectively, showing that the parameters converge with increasing quality of the
quantum levels. In spite of numerical differences, the interpretation of the
electronic structure changes occurring for these vibrations is the same for all
three quantum levels. Accurate determination of charge transfer
counterpolarization effects is important for properly describing electron density
changes for small molecular distortions.
PMID- 29959584
TI - The Standard Genetic Code can Evolve from a Two-Letter GC Code Without
Information Loss or Costly Reassignments.
AB - It is widely agreed that the standard genetic code must have been preceded by a
simpler code that encoded fewer amino acids. How this simpler code could have
expanded into the standard genetic code is not well understood because most
changes to the code are costly. Taking inspiration from the recently synthesized
six-letter code, we propose a novel hypothesis: the initial genetic code
consisted of only two letters, G and C, and then expanded the number of available
codons via the introduction of an additional pair of letters, A and U. Various
lines of evidence, including the relative prebiotic abundance of the earliest
assigned amino acids, the balance of their hydrophobicity, and the higher GC
content in genome coding regions, indicate that the original two nucleotides were
indeed G and C. This process of code expansion probably started with the third
base, continued with the second base, and ended up as the standard genetic code
when the second pair of letters was introduced into the first base. The proposed
process is consistent with the available empirical evidence, and it uniquely
avoids the problem of costly code changes by positing instead that the code
expanded its capacity via the creation of new codons with extra letters.
PMID- 29959586
TI - The contribution of livestock to urban resilience: the case of Bamako, Mali.
AB - Urban livestock keeping is increasing in many sub-Saharan African cities, but
detailed contextual information on its extent, challenges, and potential is
limited. A cross-sectional household study was done in 2010 in Bamako, Mali.
Thirty-two of 67 quarters were randomly selected with selection probability
proportional to the size of the human population of the communes. Questionnaire
interviews were done with a head of household in 1141 households, comprising
19,816 people in total. Sheep were kept by 16% (95% CI 14-18), while 21% (95% CI
17-24) kept poultry. The sheep to human ratio was 4:100, with an extrapolated
city-wide population of 67,636 sheep (95% CI 61,018-75,595). The poultry to human
ratio was 11:100, with an extrapolated city-wide population of 191,802 chickens
(95% CI 176,212-208,772). For urban livestock holders, household-level enterprise
gross margins were calculated for sheep production at USD 103 and poultry
production at USD 50 annually. The annual gross margin was estimated at USD 35
per sheep and USD 17 per chicken. Based on these figures, the city-wide urban
livestock total gross margin for Bamako in 2010 was estimated at USD 5.6 million.
Detailed population data help clarify the urban livestock animal human interface
in diverse contexts and highlight the important contributions that urban small
holder production adds to food security and resilience. The potential for urban
livestock production informs decision-makers in developing adapted, sustainable
policies in resource-constrained environments.
PMID- 29959585
TI - Concurrent modifications in the three homeologs of Ms45 gene with CRISPR-Cas9
lead to rapid generation of male sterile bread wheat (Triticum aestivum L.).
AB - KEY MESSAGE: Hexaploid bread wheat is not readily amenable to traditional
mutagenesis approaches. In this study, we show efficient utilization of CRISPR
Cas system and Next Generation Sequencing for mutant analysis in wheat.
Identification and manipulation of male fertility genes in hexaploid bread wheat
is important for understanding the molecular basis of pollen development and to
obtain novel sources of nuclear genetic male sterility (NGMS). The maize Male
sterile 45 (Ms45) gene encodes a strictosidine synthase-like enzyme and has been
shown to be required for male fertility. To investigate the role of Ms45 gene in
wheat, mutations in the A, B and D homeologs were produced using CRISPR-Cas9. A
variety of mutations in the three homeologs were recovered, including a plant
from two different genotypes each with mutations in all three homeologs. Genetic
analysis of the mutations demonstrated that all three wheat Ms45 homeologs
contribute to male fertility and that triple homozygous mutants are required to
abort pollen development and achieve male sterility. Further, it was demonstrated
that a wild-type copy of Ms45 gene from rice was able to restore fertility to
these wheat mutant plants. Taken together, these observations provide insights
into the conservation of MS45 function in a polyploid species. Ms45 based NGMS
can be potentially utilized for a Seed Production Technology (SPT)-like hybrid
seed production system in wheat.
PMID- 29959587
TI - Neuroprotective effects of dietary borax in the brain tissue of rainbow trout
(Oncorhynchus mykiss) exposed to copper-induced toxicity.
AB - We aimed to investigate the modulating effects of dietary borax on the pathways
in rainbow trout brain exposed to copper. For this aim, a comprehensive
assessment was performed including biochemical (acetylcholinesterase (AChE),
malondialdehyde (MDA), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine (8
OHdG), and caspase-3 levels) and transcriptional parameters (heat shock protein
70 (HSP70) and cytochromes P450 (CYP1A), glutathione peroxidase (gpx), superoxide
dismutase (sod), and catalase (cat)) parameters and immunohistochemically
staining of 8-OHdG. Special fish feed diets were prepared for the trial. These
diets contained different concentrations of borax (1.25, 2.5, and 5 mg/kg) and/or
copper (500 and 1000 mg/kg) at the period of pre- and co-treatment strategies for
21 days. At the end of the treatment periods, brain tissue was sampled for each
experimental group. As a result, the biochemical parameters were increased and
AChE activity decreased in the copper and copper-combined groups in comparison
with the control group and also with only borax applications (p < 0.05). We
observed an increase or decrease in particular biochemical parameters for the
borax group in every application and we established that borax had protective
effect against copper toxicity by decreasing and/or increasing the relevant
biochemical parameters in brain tissue of fish. The biochemical results of borax
and its combinations corresponded to the observations of gene expression data,
which similarly concluded that HSP70 and CYP1A genes were strongly induced by
copper (p < 0.05). In addition, the expression levels of the sod, cat, and gpx
genes in the fish brains exposed to borax and the borax combination groups were
significantly higher than the only copper-treated groups. In conclusion, borax
supplementation provided significant protection against copper-induced
neurotoxicity in trout.
PMID- 29959588
TI - SDQ in the Hands of Fathers and Preschool Teachers-Psychometric Properties in a
Non-clinical Sample of 3-5-Year-Olds.
AB - The Strengths and Difficulties Questionnaire (SDQ) is a well-established
instrument for measuring social and behavioural problems among children, with
good psychometric properties for older children, but less validity reports on pre
schoolers. In addition, there is a knowledge gap concerning fathers as
informants. The present work is one of the few validity studies to include
preschool teachers and the first on preschool children where fathers are included
as separate informants. In this study, SDQs were collected from a large community
sample (n = 17,752) of children aged 3-5, rated by mothers, fathers, and
preschool teachers and analysed using confirmatory factor analysis. Our results
revealed acceptable fit for all informant groups and measurement invariance
across child gender, child age, and parental education level. Our findings
suggest good construct validity of the SDQ for a non-clinical preschool
population and imply that it may be used for assessing child behaviour problems
from different informant perspectives.
PMID- 29959589
TI - The Interactive Effects of Parental Knowledge with Impulsivity and Sensation
Seeking in Adolescent Substance Use.
AB - This study examined whether interactions of parental knowledge of adolescent's
whereabouts with impulsivity and sensation seeking in the prediction of
adolescent substance use supported the diathesis-stress or differential
susceptibility model in 230 15-year old adolescents (53% girls). Interactions
between impulsivity and parental knowledge supported the diathesis-stress model
with high impulsivity as a vulnerability factor: when impulsivity was higher, low
levels of parental knowledge were associated with higher levels of substance use.
Interactions between sensation seeking and parental knowledge supported
differential susceptibility with low sensation seeking as a susceptibility
factor; low parental knowledge was associated with higher substance use and high
parental knowledge with lower substance use when sensation seeking was lower. Our
results show that impulsivity and sensation seeking should be considered
independently. Results support previous research suggesting that impulsivity in
adolescence may act as a vulnerability factor and suggests that low sensation
seeking may be a susceptibility factor.
PMID- 29959590
TI - BODIPY for photodynamic therapy applications: computational study of the effect
of bromine substitution on 1O2 photosensitization.
AB - Density functional theory and its time-dependent extension (DFT, TDDFT) were
employed to establish the feasibility of using a series of 4,4-difluoro-4-bora
3a,4a-diaza-s-indacenes (BODIPYs) in photodynamic therapy. Their absorption
electronic spectra, singlet-triplet energy gaps, and spin-orbit matrix elements
were computed and are discussed here. The effects of bromine substitution on the
photophysical properties of BODIPY were elucidated. The investigated compounds
were found to possess different excited triplet states that lie below the energy
of the bright excited singlet state (S1 or S2), depending on the positions
occupied by the bromine atoms. The computed spin-orbit matrix elements for the
radiationless intersystem crossing Sn -> Tm and the relative singlet-triplet
energy gaps allowed the prediction of plausible nonradiative decay pathways for
the production of singlet excited molecular oxygen, the key cytotoxic agent in
photodynamic therapy. Graphical Abstract The photophysical properties affected by
the presence of bromine atoms in different positions of a BODIPY core have been
here elucidated. In particular it has been found that SOC values strongly depend
on the position of heavy atoms into the BODIPY core, suggesting positions 1 and 7
as the best ones to enhance the ISC kinetics.
PMID- 29959592
TI - miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal
stem cells by regulating LIFR.
AB - MicroRNAs are members of the family of non-coding small RNAs that regulate gene
expression either by inhibiting mRNA translation or by promoting mRNA degradation
at the post-transcriptional level. They play an important role in the
differentiation of human bone marrow mesenchymal stem cells (hMSCs) into
adipocytes. However, the role of microRNAs in this process remains to be poorly
understood. Here, we observed that miR-377-3p expression was markedly decreased
during adipogenic differentiation of hMSCs. Overexpression of miR-377-3p
decreased adipocyte differentiation and downregulated the expression of
adipogenic markers. Meanwhile, bioinformatics-based studies suggested that LIFR
is a target of miR-377-3p. Further analysis confirmed that expression of LIFR
present markedly increased during adipogenic differentiation of hMSCs. In
addition, downregulation expression of LIFR significantly inhibited the process
of adipocyte differentiation. To confirm the relation between miR-377-3p and
LIFR, luciferase reporter assays were carried out. The results indicated that miR
377-3p bound directly to the 3'-untranslated region of LIFR. These data indicate
that miR-377-3p suppressed adipogenesis of hMSCs by targeting LIFR, which
provides novel insights into the molecular mechanism of miRNA-mediated cellular
differentiation.
PMID- 29959594
TI - Entrapment of a circular mapping catheter in a pulmonary vein during atrial
fibrillation ablation.
PMID- 29959591
TI - Acute Flaccid Paralysis and Enteroviral Infections.
AB - PURPOSE OF REVIEW: The focus of this review is on enterovirus (EV)-associated
acute flaccid paralysis (AFP) due to spinal cord anterior horn cell disease.
Emphasis is placed on the epidemiology, pathogenesis, diagnosis, treatment, and
outcome of AFP caused by polioviruses, vaccine-derived polioviruses, EV-D68, and
EV-A71. RECENT FINDINGS: Since the launch of The Global Polio Eradication
Initiative in 1988, the worldwide incidence of polio has been reduced by 99.9%,
with small numbers of poliomyelitis cases being reported only in Afghanistan,
Pakistan, and Nigeria. With the planned phaseout of oral polio vaccine, vaccine
associated poliomyelitis is also expected to be eliminated. In their place, other
EVs, chiefly EV-D68 and EV-A71, have emerged as the principal causes of AFP.
There is evidence that the emergence of EV-D68 as a cause of severe respiratory
disease and AFP was due to recent genetic virus evolution. Antiviral medications
targeting EV-D68, EV-A71, and other EVs will likely be available in the near
future. An effective EV-A71 vaccine has been developed, and preliminary
investigations suggest an EV-D68 vaccine could be on the horizon. The eradication
of poliomyelitis and vaccine-associated poliomyelitis is near, after which other
EVs, presently EV-D68 and EV-A71, will be the principle viral causes of AFP.
Moving forward, it is essential that EV outbreaks, in particular those associated
with neurologic complications, be investigated carefully and the causal strains
identified, so that treatment and prevention efforts can be rapidly developed and
implemented.
PMID- 29959593
TI - Management of VEGF-Targeted Therapy-Induced Hypertension.
AB - PURPOSE OF REVIEW: From a physiological point of view, VEGFs (vascular
endothelial growth factors) and their receptors (VEGFR) play a critical role in
vascular development angiogenesis, endothelial function, and vascular tone. On
the pathological side, VEGF-VEGFR signaling may induce dysregulated angiogenesis,
which contributes to the growth and to the spread of tumors, being essential for
neoplastic proliferation and invasion. RECENT FINDINGS: Pharmacological
inhibition of VEGF-VEGFR is now a cornerstone in the treatment of many
malignancies; however, treatment with VEGF inhibitors is commonly associated with
an increase in blood pressure values. This side effect is strictly connected with
the mechanism of action of these medications and might represent an index of
therapy efficacy. The optimal management of this form of hypertension is, at
present, not clear. Calcium channel blockers and renin-angiotensin system
inhibitors probably represent the most appropriate classes of hypertensive dugs
for the treatment of this condition; however, no conclusive data are presently
available.
PMID- 29959595
TI - Evaluation of an ex vivo porcine model to investigate the effect of low abrasive
airpolishing.
AB - OBJECTIVES: Evaluation of an ex vivo porcine model to investigate the influence
of periodontal instrumentation on soft tissue. MATERIAL AND METHODS: In each of
120 pig mandibles, one molar tooth was chosen at random and instrumented. For
subgingival debridement, two different low abrasive airpolishing powders (glycine
d90 = 25 MUm, erythritol d90 = 14 MUm, n = 30 teeth each), curets, and a
piezoelectric ultrasonic scaler were used (n = 30 teeth each). Thirty teeth in 30
other mandibles served as the untreated control. Gingival biopsies were
histologically assessed for destruction using a four-graded scale. RESULTS: The
porcine model was deemed suitable for the planned investigation. Hand
instrumentation and ultrasonic scaling caused higher tissue damage than both low
abrasive airpolishing modes (Fisher's exact test, p = 0.0025). Glycine powder led
to less, yet non-statistical noticeable gingival changes compared to erythritol
based powder (Fisher's exact test, p = 0.39). CONCLUSION: An animal model using
pig jaws may be used as a preliminary model to analyze histological effects of
periodontal instrumentation in advance of studies performed in human tissues.
Among the techniques assessed, low abrasive airpolishing (LAA) caused the
smallest tissue damage. CLINICAL RELEVANCE: To avoid gingival damage using LAA,
histological observations of gingival tissue are needed. Since numerous powders
for LAA have been developed and it may be expected that additional products will
follow, it appears to be useful to establish ex vivo animal models to prove the
powders safety.
PMID- 29959597
TI - Variable impact by ambient temperature on fatigue resistance of heat-treated
nickel titanium instruments.
AB - OBJECTIVES: The purpose of this study was to evaluate the effect of different
ambient temperatures on cyclic fatigue (CF) life of two NiTi rotary systems and
correlate the results with martensitic transformation temperatures. MATERIALS AND
METHODS: Heat-treated NiTi Vortex Blue (VB) and EdgeSequel Sapphire (SP)
instruments (tip sizes no. 20, 25, 30, 35, 40) were tested for CF resistance at
room and body temperature (n = 20 each group) in a simulated canal (angle of
curvature 60 degrees ; radius 3 mm; center from instrument tip 4.5 mm) with a
motor controlled by an electric circuit. Mean half-life, beta and eta Weibull
parameters were determined and compared. Two further instruments of each brand
were subjected to differential scanning calorimetry (DSC). RESULTS: Temperature
had an effect on fatigue behavior: all instruments lasted significantly longer at
room than at body temperature. All VB significantly outlasted those of SP at body
temperature; while smaller diameters of VB (size no. 20) were also significantly
more resistant than SP when tested at room temperature; SP with larger diameters
(sizes no. 30, no. 35, and no. 40) lasted significantly longer than VB did.
CONCLUSIONS: Immersion in water at body temperature was associated with a marked
decrease in the fatigue life of all rotary instruments tested. VB instruments
were significantly more CF resistant at body temperature and showed the highest
predictability in terms of fracture resistance. CLINICAL RELEVANCE: Rotary
instruments manufactured with different post-machining heat treatment responded
differently to changed ambient temperatures. DSC assessment of martensitic
conversion temperatures helps to predict the behavior of nickel titanium rotaries
in different environments.
PMID- 29959596
TI - Biological complications of removable dental prostheses in the moderately reduced
dentition: a systematic literature review.
AB - OBJECTIVES: The aim of the present study was a systematic review and subsequent
meta-analysis on biological complications of removable prostheses in the
moderately reduced dentition. MATERIALS AND METHODS: A systematic literature
search in established medical databases (MEDLINE, EMBASE, BIOSIS, SciSearch,
Cochrane, FIZ Technik Web) and a hand search of relevant dental journals was
conducted. The search terms were relevant MeSH terms, free search terms, and
combinations of the two. The search included randomized controlled trials,
prospective and retrospective studies with data on biological complications of
removable dental prostheses in the moderately reduced dentition with at least 15
participants, an observation period of at least 2 years, and a drop-out rate of
less than 25%. The selection of relevant publications was carried out at the
title, abstract, and full-text level by at least two of the authors involved. The
publications included were tabulated and analyzed. RESULTS: Of the original
12,994 matches, 1923 were analyzed by title, 650 by abstract, and 111 according
to the full text. A total of 42 publications were ultimately included. The
following parameters were evaluated. TOOTH LOSS: Results varied, depending on the
observation period, between 0 and 18.1% for clasp-retained removable dental
prostheses (RDPs), between 5.5 and 29% for attachment-retained RDPs, and between
5.5 and 51.7% for double crown-retained RDPs. CARIES: Results varied, depending
on the observation period, between 0 and 32.7% for clasp-retained RDPs, between
1.8 and 29% for attachment-retained RDPs, and between 1.8 and 16.4% for double
crown-retained RDPs. ENDODONTIC TREATMENT: Results varied, depending on the
observation period, between 3.5 and 19.2% for clasp-retained RDPs, between 6.9
and 16.4% for attachment-retained RDPs, and between 0.6 and 13.9% for double
crown-retained RDPs. TOOTH FRACTURE: Results varied, depending on the observation
period, between 1.7 and 5.3% for clasp-retained RDPs, between 12.7 and 40% for
attachment-retained RDPs, and between 0.4 and 4.4% for double crown-retained
RDPs. TOOTH MOBILITY: There were no changes or improvements for clasp-retained
RDPs. The better the pre-treatment and supportive care is, the smaller the
differences are. For double crown-retained RDPs, a slight increase was found in
one study. The results for the parameters probing depth and radiological bone
loss were inconclusive. GINGIVAL RECESSION: Gingival recession seemed to be
favored by a mandibular sublingual bar. Compared to fixed restorations, removable
restorations seemed to be associated with a more pronounced need for dental
treatment. Stringent pre-treatment and supportive care reduced the complication
rates. CONCLUSIONS: Heterogeneous study designs and data analyses rendered a meta
analysis impossible, so that an evaluation at the highest level of evidence could
not be performed. CLINICAL RELEVANCE: Within the limitations of this study, it
would be correct to state that removable dental prostheses require intensive
maintenance. Suitable pre-treatment and supportive care can lower the
complication rates, in the absence of which they constitute trigger factors for
(additional) biological complications.
PMID- 29959598
TI - Detection of pulsed blood flow through a molar pulp chamber and surrounding
tissue in vitro.
AB - OBJECTIVES: Due to severe limitations of dental pulp sensitivity tests, the
direct recording of pulsed blood flow, using photoplethysmography (PPG), has been
proposed. In vivo evaluation is methodologically difficult and in vitro models
have hitherto been adversely influenced by shortcomings in emulating the in vivo
situation. Consequently, the aim of this study was to test an improved data
acquisition system and to use this configuration for recording pulsed blood in a
new model. MATERIALS AND METHODS: We introduced a PPG signal detection system by
recording signals under different blood flow conditions at two wavelengths (625
and 940 nm). Pulsed blood flow signals were measured using an in vitro model,
containing a molar with a glass pulp and a resin socket, which closely resembled
in vivo conditions with regard to volumetric blood flow, pulp anatomy, and
surrounding tissue. RESULTS: The detection system showed improved signal strength
without stronger blanketing of noise. On the tooth surface, it was possible to
detect signals emanating from pulsed blood flow from the glass pulp and from
surrounding tissue at 625 nm. At 940 nm, pulp derived signals were recorded,
without interference signals from surrounding tissue. CONCLUSION: The PPG-based
method has the potential to detect pulsed blood flow in small volumes in the pulp
and (at 625 nm) also in adjacent tissues. CLINICAL RELEVANCE: The results show
the need for clear differentiation of the spatial origins of blood flow signals
of any vitality test method to be applied to teeth.
PMID- 29959599
TI - Needle fracture as a complication of dental local anesthesia: recommendations for
prevention and a comprehensive treatment algorithm based on literature from the
past four decades.
AB - OBJECTIVES: The aim of this publication is to provide a concept for prevention
and a standardized step-by-step clinical approach to this rare but serious and
potentially preventable complication of dental local anesthesia. MATERIALS AND
METHODS: We collected data with a PUBMED search using the key words "local
anesthesia," "dental anesthesia/anesthesia" OR "mandibular block anesthesia,"
"complication," "hypodermic needle," "needle breakage" OR "needle fracture," and
"foreign body AND removal" OR "retrieval." The existing literature was
systematically evaluated from 1980 to date using Microsoft Excel 2007 (Microsoft
Corporation). RESULTS: After analysis of the literature, we included 36 reports
documenting 59 needle breakage events and defined possible risk factors and
preventive measures. All relevant reported parameters were listed in tabular
form. The main result of this article is a treatment algorithm for this
complication. CONCLUSIONS: Prevention of a needle fracture should be the main
goal during local dental anesthesia. Use of longer hypodermic needle can obviate
complex retrieval surgery. If immediate removal of the fragment fails,
localization, planning, and the necessary surgical procedure should be arranged
promptly. CLINICAL RELEVANCE: Following a strict algorithm, successful surgical
handling of this complication will depend on minimizing risk and following
treatment recommendations closely.
PMID- 29959600
TI - Maternal Socioeconomic Mobility and Preterm Delivery: A Latent Class Analysis.
AB - Objective Growing evidence suggests that maternal socioeconomic mobility (SM) is
associated with pregnancy outcomes. Our study investigated the association
between maternal SM from childhood to adulthood and the risk of preterm delivery
(PTD), and examined heterogeneity of associations by race/ethnicity. Methods In
this study, 3019 pregnant women enrolled from 5 Michigan communities at 16-27
weeks' gestation (1998-2004) provided their parents' socioeconomic position (SEP)
indicators (education, occupation, receipt of public assistance) and their own
and child's father's SEP indicators (education, occupation, Medicaid status, and
household income) at the time of enrollment. Latent class analysis was used to
identify latent classes of childhood SEP indicators, adulthood SEP indicators,
and SM from childhood to adulthood, respectively. A model-based approach to
latent class analysis with distal outcome assessed relations between latent class
and PTD, overall and within race/ethnicity groups. Results Three latent classes
(low, middle, high) were identified for childhood SEP indicators and adulthood
SEP indicators, respectively; while four latent classes (static low, upward,
downward, and static high) best described SM. Women with upward SM had decreased
odds of PTD (Odds ratio = 0.60, 95% confidence interval: 0.42, 0.87), compared to
those with static low SEP. This SM advantage was true for all women and most
pronounced in white/others women. Conclusions Maternal experiences of upward SM
may be important considerations when assessing PTD risk. Our results support the
argument that policies and programs aimed at improving women's SEP could lower
PTD rates.
PMID- 29959601
TI - Improving cognitive task in kindled rats by using low frequency stimulation
during epileptogenesis.
AB - Numerous studies indicate that one of the bad effects of epilepsy is cognitive
impairment. In this study we focused on the effect of LFS as a potential
anticonvulsant agent, during epileptogenesis on cognitive impairments induced by
amygdala kindling in rat. Twenty-one adult rats were divided into 3 groups
including control (n = 7), kindled (n = 7), and Kindled+LFS (KLFS) (n = 7).
Animals in the kindled group received kindling stimulation in a rapid kindling
manner (a 3 s train of 50 Hz monophasic pulses of 1 ms duration, 12 times a day)
in amygdala whereas control animals had no stimulation. Four packages of LFS
(each package consisting of 200 monophasic square pulses, 0.1 ms pulse duration
at 1 Hz) were applied daily after termination of kindling stimulation in KLFS
group. Spatial memory of all animals was tested using radial arm maze after
termination of stimulation on acquisition trial days and 14 days after the final
acquisition trial test. Epileptogenesis process significantly increased working
and reference memory error compared to control groups whereas application of LFS
immediately after kindling stimulation prevented this impairment in 8 arm radial
maze and there was no significant difference between KLS and control groups. Our
results indicated that application of LFS during kindling acquisition suppresses
memory impairment in epileptogenesis by kindling stimulation.
PMID- 29959602
TI - The Influence of Dyslexia Candidate Genes on Reading Skill in Old Age.
AB - A number of candidate genes for reading and language impairment have been
replicated, primarily in samples of children with developmental disability or
delay, although these genes are also supported in adolescent population samples.
The present study used a systematic approach to test 14 of these candidate genes
for association with reading assessed in late adulthood (two cohorts with mean
ages of 70 and 79 years). Gene-sets (14 candidates, axon-guidance and neuron
migration pathways) and individual SNPs within each gene of interest were tested
for association using imputed data referenced to the 1000 genomes European panel.
Using the results from the genome-wide association (GWA) meta-analysis of the two
cohorts (N = 1217), a competitive gene-set analysis showed that the candidate
gene-set was associated with the reading index (p = .016) at a family wise error
rate corrected significance level. Neither axon guidance nor neuron migration
pathways were significant. Whereas individual SNP associations within CYP19A1,
DYX1C1, CNTNAP2 and DIP2A genes (p < .05) did not reach corrected significance
their allelic effects were in the same direction as past available reports. These
results suggest that reading skill in normal adults shares the same genetic
substrate as reading in adolescents, and clinically disordered reading, and
highlights the utility of adult samples to increase sample sizes in the genetic
study of developmental disorders.
PMID- 29959603
TI - Naive Bayesian Models for Vero Cell Cytotoxicity.
AB - PURPOSE: To advance translational research of potential therapeutic small
molecules against infectious microbes, the compounds must display a relative lack
of mammalian cell cytotoxicity. Vero cell cytotoxicity (CC50) is a common initial
assay for this metric. We explored the development of naive Bayesian models that
can enhance the probability of identifying non-cytotoxic compounds. METHODS: Vero
cell cytotoxicity assays were identified in PubChem, reformatted, and curated to
create a training set with 8741 unique small molecules. These data were used to
develop Bayesian classifiers, which were assessed with internal cross-validation,
external tests with a set of 193 compounds from our laboratory, and independent
validation with an additional diverse set of 1609 unique compounds from PubChem.
RESULTS: Evaluation with independent, external test and validation sets indicated
that cytotoxicity Bayesian models constructed with the ECFP_6 descriptor were
more accurate than those that used FCFP_6 fingerprints. The best cytotoxicity
Bayesian model displayed predictive power in external evaluations, according to
conventional and chance-corrected statistics, as well as enrichment factors.
CONCLUSIONS: The results from external tests demonstrate that our novel
cytotoxicity Bayesian model displays sufficient predictive power to help guide
translational research. To assist the chemical tool and drug discovery
communities, our curated training set is being distributed as part of the
Supplementary Material. Graphical Abstract Naive Bayesian models have been
trained with publically available data and offer a useful tool for chemical
biology and drug discovery to select for small molecules with a high probability
of exhibiting acceptably low Vero cell cytotoxicity.
PMID- 29959604
TI - Risk of diabetes complications among those with diabetes receiving androgen
deprivation therapy for localized prostate cancer.
AB - PURPOSE: Androgen deprivation therapy (ADT), used increasingly in the treatment
of localized prostate cancer, is associated with substantial long-term adverse
consequences, including incident diabetes. While previous studies have suggested
that ADT negatively influences glycemic control in existing diabetes, its
association with diabetes complications has not been investigated. In this study,
we examined the association between ADT use and diabetes complications in
prostate cancer patients. METHODS: A retrospective cohort study was conducted
among men with newly diagnosed localized prostate cancer between 1995 and 2008,
enrolled in three integrated health care systems. Men had radical prostatectomy
or radiotherapy (curative intent therapy), existing type II diabetes mellitus
(T2DM), and were followed through December 2010 (n = 5,336). Cox proportional
hazards models were used to examine associations between ADT use and diabetes
complications (any complication), and individual complications (diabetic
neuropathy, diabetic retinopathy, diabetic amputation or diabetic cataract) after
prostate cancer diagnosis. RESULTS: ADT use was associated with an increased risk
of any diabetes complication after prostate cancer diagnosis (adjusted hazard
ratio, AHR, 1.12, 95% CI 1.03-1.23) as well as an increased risk of each
individual complication compared to non-use. CONCLUSION: ADT use in men with
T2DM, who received curative intent therapy for prostate cancer, was associated
with an increased risk of diabetes complications. These findings support those of
previous studies, which showed that ADT worsened diabetes control. Additional,
larger studies are required to confirm these findings and to potentially inform
the development of a risk-benefit assessment for men with existing T2DM, before
initiating ADT.
PMID- 29959606
TI - Coalitional Play Fighting and the Evolution of Coalitional Intergroup Aggression.
AB - Dyadic play fighting occurs in many species, but only humans are known to engage
in coalitional play fighting. Dyadic play fighting is hypothesized to build motor
skills involved in actual dyadic fighting; thus, coalitional play fighting may
build skills involved in actual coalitional fighting, operationalized as forager
lethal raiding. If human psychology includes a motivational component that
encourages engagement in this type of play, evidence of this play in forager
societies is necessary to determine that it is not an artifact of agricultural or
industrial conditions. We examine whether coalitional play fighting appears in
the hunter-gatherer record and includes motor skills used in lethal raiding.
Using the ethnographic record, we generated a list of motor patterns regularly
used in forager warfare. Then, using Murdock's Ethnographic Atlas, we identified
100 culture clusters containing forager societies and searched the ethnographic
records of these societies for descriptions of coalitional play fighting,
operationalized as contact games played in teams. Resulting games were coded for
the presence of eight motor patterns regularly used in forager lethal raiding.
Although play does not tend to be systematically documented in the hunter
gatherer literature, sufficiently detailed descriptions of coalitional play were
found for 46 of the 100 culture clusters: all 46 exhibited coalitional play using
at least one of the predicted motor patterns; 39 exhibited coalitional play using
four or more of the eight predicted motor patterns. These results provide
evidence that coalitional play fighting (a) occurs across a diverse range of
hunter-gatherer cultures and habitats, (b) regularly recruits motor patterns used
in lethal raiding, and (c) is not an artifact of agricultural or industrial life.
This is a first step in a new line of research on whether human male psychology
includes motivations to engage in play that develops the deployment of
coordinated coalitional action involving key motor patterns used in lethal
raiding.
PMID- 29959605
TI - Primary Prevention of Clostridium difficile-Associated Diarrhea: Current
Controversies and Future Tools.
AB - PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is a major cause of
morbidity and mortality in hospitalized patients and rates in most places have
not decreased significantly despite broad efforts by both hospitals and public
health entities. This review aims to provide readers with a better understanding
of the limitations of current prevention strategies. We also review potential
future tools that may be available for the primary prevention of CDI in the next
decade. RECENT FINDINGS: Research over the last decade has expanded our
appreciation of the role of asymptomatic shedding in the healthcare setting and
in the community. This review demonstrates that poor quality data underlies even
well-established guidance from national authorities on basic topics such as
contact precautions, avoidance of alcohol-based hand hygiene products, CDI
testing, supplemental cleaning modalities, and the use of bleach solutions.
Additionally, we review research on novel preventative interventions such as
identification of asymptomatic carriers, supplemental environmental cleaning
technologies, vaccines, and the manipulation of the intestinal microbiome. While
there is preliminary data that supports further research in all of these areas,
the research is not yet robust enough on which to base local or national policy
recommendations, though late-phase human clinical trials of CDI vaccine trials
are ongoing. Over the last decade, researchers have begun to reassess the
traditional infection prevention model for CDI. Data suggesting a greater role
for asymptomatic shedders has increased our understanding of current vertical
prevention techniques and is forcing researchers to look more at new processes
and technologies to decrease disease incidence.
PMID- 29959607
TI - An Improved Two-Layer Authentication Scheme for Wireless Body Area Networks.
AB - Wireless body area networks (WBANs) comprises a number of sensor nodes and the
portable mobile device such as smartphone. It is used to monitor the physical
condition and provide a reliable healthcare system. Utilizing the wireless
communication network, sensor nodes collect the physiological data of one patient
to the portable mobile device and the latter analyzes and transmits them to the
application providers. Therefore, the personal data confidentiality and user
privacy are cores of WBANs. Recently, Shen et al. presented a multi-layer
authentication protocol for WBANs, which is lightweight and much easier to
implement. However, we observe that their authentication between sensor nodes and
the portable mobile device could ensure the forward security property only when
the sensor nodes are changed (add or delete). When the sensor nodes are constant,
the security property is not satisfied. Meanwhile, the authentication between the
portable mobile device and application provider is prone to mutual impersonation
attack, so the critical goal of mutual authentication can not be achieved. In
this paper, an improved two-layer authentication scheme is proposed to remove the
flaws. The analysis shows that our method is more secure and could withstand
various attacks.
PMID- 29959608
TI - Knowledge of risk factors and prevention of osteoporosis: the Israeli women's
health at midlife study.
AB - : Wide disparities in knowledge of risk factors and prevention of osteoporosis
were demonstrated among midlife Israeli minority women (Arabs and immigrants from
the former USSR) compared to Jewish long-time residents. Women who believed
osteoporosis to be a serious disease and those who felt susceptible to it
reported better knowledge. PURPOSE: The main goals of this study were to assess
knowledge of risk factors and preventive measures for osteoporosis in middle-aged
women and to evaluate the relationship of knowledge to personal risk factors and
personal perceptions about osteoporosis. METHODS: Face-to-face interviews with
women aged 45-64 years were conducted during 2004-2006 within three population
groups: long-term Jewish residents (LTJRs), immigrants from the former Soviet
Union, and Arab women. The survey instrument included five knowledge statements
related to the risk after menopause, the risk of smoking, family history of
fractures, decreased risk by physical activity, and by use of medications.
RESULTS: The findings indicated wide disparities in knowledge about risk factors
and preventive behavior of osteoporosis between the two minority groups
(immigrants from the former Soviet Union and Arab women) and the majority group
of midlife Israeli women. Knowledge of osteoporosis was related to perceived
severity of the disease and partly to perceived susceptibility to osteoporosis.
Past diagnosis of osteoporosis, current or past smoking status, and BMI were
unrelated to knowledge in multivariate analyses. CONCLUSIONS: There is a need to
improve knowledge of osteoporosis especially among less educated and minority
women. Subjective perception of risk was more strongly related to knowledge than
actual risk factors and should be targeted in public campaigns. The efforts
should be aimed at strengthening women's perception of their own susceptibility
to osteoporosis and of the severity of this disease.
PMID- 29959609
TI - Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower
respiratory infections in Indigenous Australian children.
AB - Acute lower respiratory infection (ALRI) is a major cause of hospitalization for
Indigenous children in remote regions of Australia. The associated microbiology
remains unclear. Our aim was to determine whether the microbes present in the
nasopharynx before an ALRI were associated with its onset. A retrospective case
control/crossover study among Indigenous children aged up to 2 years. ALRI cases
identified by medical note review were eligible where nasopharyngeal swabs were
available: (1) 0-21 days before ALRI onset (case); (2) 90-180 days before ALRI
onset (same child controls); and (3) from time and age-matched children without
ALRI (different child controls). PCR assays determined the presence and/or load
of selected respiratory pathogens. Among 104 children (182 recorded ALRI
episodes), 120 case-same child control and 170 case-different child control swab
pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases
compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22-7.76, p =
0.017), but this association was not significant in cases versus different child
controls (15 vs 10%; OR = 1.93, 95% CI 0.97-3.87 (p = 0.063). No other microbes
were more prevalent in cases compared to controls. Streptococcus pneumoniae
(74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly
identified across all swabs. In a pediatric population with a high detection rate
of nasopharyngeal microbes, HAdV was the only pathogen detected in the period
before illness presentation that was significantly associated with ALRI onset.
Detection of other potential ALRI pathogens was similar between cases and
controls.
PMID- 29959610
TI - Economic evaluation of micafungin versus liposomal amphotericin B (LAmB) for
treating patients with candidaemia and invasive candidiasis (IC) in Turkey.
AB - Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in
treating patients with candidaemia and invasive candidiasis (IC). The current
study aimed to evaluate the economic impact of using micafungin versus LAmB for
treatment of candidaemia and IC in Turkey. A decision analytic model, which
depicted economic consequences upon administration of micafungin or LAmB for
treating patients with candidaemia and IC in the Turkish hospitals, was
constructed. Patients were switched to an alternative antifungal agent if initial
treatment failed due to mycological persistence. All patients were followed up
until treatment success or death. Outcome probabilities were obtained from
published literature and cost inputs were derived from the latest Turkish
resources. Expert panels were used to estimate data that were not available in
the literature. Cost per patient treated for each intervention was then
calculated. Sensitivity analyses including Monte Carlo simulation were performed.
For treatment of candidaemia and IC, micafungin (?4809) was associated with
higher total cost than LAmB (?4467), with an additional cost of ?341 per treated
patient. Cost of initial antifungal treatment was the major cost driver for both
comparators. The model outcome was robust over a wide variation in input
variables except for drug acquisition cost and duration of initial antifungal
treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for
the treatment of candidaemia and IC from the Turkish hospital perspective, with
variation in drug acquisition cost of the critical factor affecting the model
outcome.
PMID- 29959611
TI - Rates of Criminal Legal System Involvement Among Patients Who Are Discharged
Against Medical Advice.
PMID- 29959612
TI - Robotic Prophylactic Nipple-Sparing Mastectomy with Immediate Prosthetic Breast
Reconstruction: A Prospective Study.
AB - BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) could be a significant
advancement in the treatment of breast cancers and prophylaxis because the
mastectomy is performed without leaving any scar on the breast. The aim of this
study was to assess the feasibility and the safety of RNSM with immediate
prosthetic breast reconstruction (IPBR). METHODS: In this prospective study, RNSM
with IPBR was offered to patients with breast cup size A, B or C and ptosis grade
<= 2. In case of oncologic surgery, RNSM was proposed only if the tumor was
located more than 2 cm away from the nipple-areola complex (NAC) and if
postoperative radiation was not indicated. In case of prophylactic surgery, RNSM
was proposed only if a high-risk genetic mutation had been identified. The
primary endpoint was the rate of skin or NAC necrosis. The rate of conversion to
open technique, the duration of the procedure, and postoperative complications
were also analyzed. RESULTS: Sixty-three RNSM with IPBR were performed in 33
patients. There were no cases of mastectomy skin flap or NAC necrosis. We had to
convert to an open technique in one case (1.6%). Three infections occurred
(4.8%), one leading to implant loss (1.6%). No other major complications were
observed. CONCLUSIONS: Preliminary data attest to the feasibility, the
reproducibility, and the safety of this approach. However, long-term data are
needed to confirm the oncological safety and the esthetic stability of the
result. Trial registration identifier NCT02673268.
PMID- 29959613
TI - Is Age Trumping Genetic Profiling in Clinical Practice? Relationship of
Chemotherapy Recommendation and Oncotype DX Recurrence Score in Patients Aged <
50 Years versus >= 50 Years, and Trends Over Time.
AB - BACKGROUND: Oncotype DX (oDX) is used to predict recurrence and indicate response
to chemotherapy in patients with early-stage breast cancer (BC). We evaluated the
relationship between age (< 50 vs. >= 50 years), recurrence score (RS),
chemotherapy use, and trends of oDX testing over time. METHODS: Using the
National Cancer Database, we identified women with T1/T2, N0, estrogen receptor
positive BC from 2009 to 2014. We stratified patients by age (< 50 and >= 50
years) and RS (low: < 18; intermediate: 18-30; and high: > 30), and compared
demographics, tumor characteristics, and chemotherapy recommendations. Management
trends were also assessed. RESULTS: From 2009 to 2014, a total of 377,725 cases
met the eligibility criteria for oDX testing; 115,052 (30.5%) patients had oDX,
and 60,804 (16.1%) were < 50 years of age. The majority had low RS and T1N0
disease. Patients < 50 years of age were more likely to be recommended
chemotherapy than those >= 50 years of age, regardless of RS (p <= 0.001), and
were more likely to ultimately undergo chemotherapy (p < 0.001). When stratified
by year, oDX utilization increased. There was a decreasing trend in chemotherapy
recommendations in both the low- and intermediate-RS groups for both age groups
(all p = 0.001), with no change in the high-RS group (< 50 years: p = 0.52; >= 50
years: p = 0.67). Univariate and multivariate analyses demonstrated that patients
< 50 years of age and those with a higher RS were more likely to be recommended
chemotherapy (p < 0.001). CONCLUSIONS: The testing of oDX in BC has significantly
increased since first implemented. Results from additional studies such as
TAILORx will clarify the current discordant practice patterns between low oDX RSs
and adjuvant chemotherapy recommendations.
PMID- 29959614
TI - Top-down matching singleton cues have no edge over top-down matching
nonsingletons in spatial cueing.
AB - In the present study, we investigated in a novel version of the peripheral-cueing
paradigm whether object salience influences attentional selection at early stages
of visual processing. In each trial, participants searched for targets of one of
two possible colors. In the most important condition, the cueing displays
consisted of a singleton cue having one target color and three additional
nonsingletons of another target color. Hence, all objects in these all-relevant
cueing displays had a target color. If singletons initially capture attention in
a stimulus-driven way, regular cueing effects (faster responses to targets at the
cued location than to targets away from the cue) should be found in these
conditions. However, the results suggested otherwise: As compared to a control
condition with a singleton cue of a target color among nonsingletons of a
nontarget color, the cueing effects in all-relevant cueing displays were strongly
reduced. This was also replicated with a very brief cue-target interval. The
results suggest top-down contingent capture of attention even during the initial
phase of processing salient stimuli, and argue against stimulus-driven capture of
attention plus subsequent rapid disengagement.
PMID- 29959615
TI - Reply to Letter to the Editor: Advanced Age and Success of Bariatric Surgery.
PMID- 29959616
TI - Item-specific processing reduces false recognition in older and younger adults:
Separating encoding and retrieval using signal detection and the diffusion model.
AB - Our study examined processing effects in improving memory accuracy in older and
younger adults. Specifically, we evaluated the effectiveness of item-specific and
relational processing instructions relative to a read-only control task on
correct and false recognition in younger and older adults using a categorized
list paradigm. In both age groups, item-specific and relational processing
improved correct recognition versus a read-only control task, and item-specific
encoding decreased false recognition relative to both the relational and read
only groups. This pattern was found in older adults despite overall elevated
rates of false recognition. We then applied signal-detection and diffusion
modeling analyses, which separately utilized recognition responses and the
latencies to those responses to estimate contributions of encoding and monitoring
processes on recognition decisions. Converging evidence from both analyses
demonstrated that item-specific processing benefits to memory accuracy were due
to improvements of both encoding (estimates of d' and drift rate) and monitoring
(estimates of lambda and boundary separation) processes, and, importantly,
occurred similarly in both younger and older adults. Thus, older and younger
adults showed similar encoding-based and test-based benefits of item-specific
processing to enhance memory accuracy.
PMID- 29959617
TI - Atraumatic splenic rupture in a peritoneal dialysis patient.
AB - Splenic hemorrhage is a potentially life-threatening complication usually
occurring after blunt trauma to the abdomen. Atraumatic splenic rupture (ASR) is
an uncommon condition, and mostly results from pathology affecting the spleen,
such as tumor infiltration or infection. Here, we report a case of atraumatic
rupture of a normal spleen in a patient undergoing peritoneal dialysis, and
review similar cases in the literature. The case involved a 58-year-old man with
nephrotic syndrome who had been undergoing peritoneal dialysis for 1 year. He
presented to the hospital with abdominal pain, nausea, and blood-stained
dialysate. Laboratory data revealed severe anemia, with a hemoglobin of 4.3 g/dL.
An abdominal computed tomography (CT) scan demonstrated a high-density area
around the spleen and malposition of the catheter. Laparoscopy revealed large
amounts of coagulated blood surrounding the spleen. The patient was diagnosed
with atraumatic splenic bleeding. He improved with bed rest and blood
transfusion, and could continue with peritoneal dialysis. It was considered that
the etiology of bleeding was directly from the spleen. However, due to the
temporary malposition of the peritoneal catheter, catheter-induced splenic trauma
could not be ruled out. ASR is a rare entity that needs a high index of suspicion
for diagnosis. Using CT scanning and peritoneal fluid analysis, these modalities
may assist in the diagnosis. Emergency intervention is required upon definitive
diagnosis. Increased awareness of ASR can enhance the early diagnosis and
effective treatment.
PMID- 29959618
TI - Paraplegia as a presentation of primary hyperoxaluria.
AB - 30% of the patients suffering from hyperoxaluria type 1 are diagnosed only when
they already had reached end-stage renal disease. We report the case of a 57-year
old woman with history of chronic kidney failure presenting with paraplegia due
to spinal cord compression by thoracic mass-like lesions. Bone biopsy specimen
obtained by decompressive laminectomy revealed calcium oxalate deposits. Once
diagnosis of primary hyperoxaluria was confirmed, she underwent haemodialysis
with incomplete improvement of her neurological disorders and was registered on
the waiting list for transplantation.
PMID- 29959619
TI - Assessment of developmental potential of human single pronucleated zygotes
derived from conventional in vitro fertilization.
AB - PURPOSE: The aim of this study was to non-invasively validate the developmental
potential of human single pronucleated (1PN) zygotes derived from conventional in
vitro fertilization (c-IVF) at the zygote stage. METHODS: Fifty 1PN zygotes
derived from 45 patients undergoing c-IVF were used. Immunohistochemistry and
fluorescence live cell imaging were used to confirm normal chromosome segregation
during the first mitosis. The usefulness of measuring pronuclear diameter was
assessed on the basis of the presence or absence of a proper first cleavage and
validated by subsequent development. RESULTS: Although approximately 80% (15/19)
of 1PN zygotes contained a diploid genome, immunohistochemistry revealed an
unequal distribution of paternal and maternal genomes at the first mitosis.
Fluorescence live imaging revealed that 73% (8/11) of 1PN zygotes formed a
functional mitotic spindle at the first mitosis resulting from diploid genomes,
with 25% (2/8) of these forming a tripolar spindle. 1PN zygotes in which the
pronucleus disappeared and that subsequently underwent cleavage had a pronuclear
diameter >= 32.2 MUm. The selection of 1PN zygotes based on pronuclear diameter
resulted in zygotes that all formed mitotic spindles with poles during cleavage.
Furthermore, 63% (5/8) of these zygotes reached the blastocyst stage.
CONCLUSIONS: This study demonstrates the usefulness of a non-invasive assessment
of 1PN zygotes derived from c-IVF as an indicator of developmental potential.
Furthermore, diploid 1PN zygotes do not always exhibit normal chromosome
segregation at the first mitosis. A pronuclear diameter >= 32.2 MUm just before
PN breakdown might be a useful criterion to assess 1PN zygotes that are capable
of further development.
PMID- 29959620
TI - Transcripts encoding free radical scavengers in human granulosa cells from
primordial and primary ovarian follicles.
AB - PURPOSE: To study the presence and distribution of genes encoding free radical
scavengers in human granulosa cells from primordial and primary ovarian
follicles. METHODS: A class comparison study on existing granulosa cell
transcriptome from primordial (n = 539 follicles) and primary (n = 261) follicles
donated by three women having ovarian tissue cryopreserved before chemotherapy
was performed and interrogated. RESULTS: In granulosa cells from primordial
follicles, 30 genes were annotated 'mitochondrial dysfunction' including
transcripts (PRDX5, TXN2) encoding enzymatic free radical scavengers
peroxiredoxin 5 and thioredoxin 2. Several apoptosis regulation genes were noted
(BCL2, CAS8, CAS9, AIFM1). In granulosa cells from primary follicles,
mitochondrial dysfunction signalling pathway was annotated. High expression of
transcripts encoding the free radical scavenger peroxiredoxin 3, as well as anti
apoptotic enzyme BCL2, was found. Interestingly, PARK7 encoding the deglycase (DJ
1) protein was expressed in granulosa cells from primary follicles. DJ-1 is
implicated in oxidative defence and functions as a positive regulator of the
androgen receptor and as a negative regulator of the phosphatidylinositol 3
kinase (PI3K)/phosphatase and tensin homolog (PTEN)/serine-threonine protein
kinase (AKT) signalling pathway suppressor PTEN. CONCLUSIONS: The results
indicate extensive energy production and free radical scavenging in the granulosa
cells of primordial follicles with potential implications for ovarian ageing,
cigarette smoking, premature ovarian failure and polycystic ovarian syndrome.
Furthermore, DJ-1 may be involved in androgen responsiveness and the regulation
of follicle growth via PI3K/PTEN/AKT signalling pathway regulation in the
granulosa cells of primary follicles. The involvement of mitochondrial free
radical production in the age-related decline of competent oocytes is becoming
apparent.
PMID- 29959622
TI - William C. Eckelman, PhD (born 1941).
PMID- 29959621
TI - Superovulation alters the expression of endometrial genes critical to tissue
remodeling and placentation.
AB - PURPOSE: Epidemiologic data suggest that in vitro fertilization (IVF) is
associated with an increased risk of disorders of placentation including
preeclampsia and fetal growth restriction. Specifically, studies have
demonstrated that singleton pregnancies conceived following a fresh embryo
transfer are at an increased risk of delivering an infant with low birth weight
compared to those conceived following a frozen embryo transfer. The mechanism
responsible for this association remains unclear. Procedures utilized in IVF have
also been linked with epigenetic changes and gene expression changes in both
fetal and maternal tissues. Data suggest that modifications in the maternal
endometrium can lead to disordered trophoblast invasion and placentation. This
study examines the effect of ovarian stimulation on endometrial gene expression
and DNA methylation during the window of implantation to examine potential
pathways playing a role in the adverse outcomes associated with IVF. METHODS:
Endometrial biopsies were obtained from oocyte donors and age-matched naturally
cycling women 11 days following oocyte retrieval in donors or 12 days following
luteinizing hormone (LH) surge in naturally cycling women. Global gene expression
was analyzed via Affymetrix Human Gene 1.1 ST array and confirmed with RT-qPCR.
DNA methylation was assessed with the Infinium DNA methylation 450 K BeadChip.
RESULTS: Analysis of endometrial gene expression from 23 women (11 oocyte donors
and 12 controls) demonstrated 165 genes with a greater than twofold change in
expression between donors and controls. While there were 785 genes with
significant differential methylation in the endometrium of donors when compared
with control subjects, none of the genes with altered expression showed
significant changes in DNA methylation. Analysis of the differentially expressed
genes showed enrichment for genes involved in endometrial remodeling including
PLAT, HSPE2, MMP2, and TIMP1. Validation studies using RT-qPCR found a 73%
reduction in expression of heparanase 2 (HSPE2) an enzyme associated with both
angiogenesis and cell invasion, a greater than twofold increase in tissue-type
plasminogen activator (PLAT), a serine protease participating in matrix
degradation, and a 70% increase in MMP2, a gelatinase involved in collagen and
fibronectin breakdown. CONCLUSIONS: Superovulation alters expression of genes
critical to endometrial remodeling during early implantation. Such changes could
lead to altered trophoblast migration and impaired endovascular invasion. These
findings offer a potential mechanism for the adverse perinatal outcomes observed
following embryo transfer during fresh IVF cycles.
PMID- 29959623
TI - Astragaloside IV Inhibits Cigarette Smoke-Induced Pulmonary Inflammation in Mice.
AB - The aim of this study was to investigate the effects of Astragaloside IV (AS) on
cigarette smoke (CS)-induced chronic obstructive pulmonary disease (COPD). Our
results showed that AS alleviated CS-induced pathological injury in lung tissue.
AS also increased superoxide dismutase (SOD) and reduced the level of
malondialdehyde (MDA) in serum and lung. AS also reduced cytokines including
tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin
1beta (IL-1beta) in serum and lung. More, AS significantly reduced the protein
expression of JAK3/STAT3/NF-kappaB pathway in CS-induced mice. In vitro,
cigarette smoke extract (CSE) stimulation exposed to normal human bronchial
epithelial (HBE) cells. Results further confirmed that AS significantly inhibited
the protein levels of JAK3/STAT3/NF-kappaB pathway in CSE-induced HBE. Our result
showed that AS might effectively ameliorate COPD via JAK3/STAT3/NF-kappaB
pathway.
PMID- 29959624
TI - Combination Therapy with Curcumin Alone Plus Piperine Ameliorates Ovalbumin
Induced Chronic Asthma in Mice.
AB - Allergic asthma is an inflammatory condition accompanied by inflammation as well
as oxidative stress. Supplementation of an anti-inflammatory agent having
antioxidant properties may have therapeutic effects against this disease. Over
the recent decades, the interest in combination therapy as new alternative
medication has increased and it offers numerous benefits along with noticeable
lack of toxicity as well as side effects. In this study, protective effects of
curcumin alone and in combination with piperine were evaluated in mouse model of
allergic asthma. Balb/c mice were sensitized on days 0, 7, and 14 and challenged
from days 16-30 on alternate days with ovalbumin (OVA). Mice were pretreated with
curcumin (Cur; 10 and 20 mg/kg) and piperine (Pip; 5 mg/kg) alone and in
combination via the intraperitoneal route on days 16-30 and compared with
intranasal curcumin (5 mg/kg) treatment. Blood, bronchoalveolar lavage fluid
(BALF), and lungs were collected after mice were sacrificed on day 31st. Mice
immunized with OVA have shown significant increase in airway inflammation and
oxidative stress as determined by oxidative stress markers. A significant
suppression was observed with all the treatments, but intranasal curcumin
treatment group has shown maximum suppression. So, among all the treatment
strategies utilized, intranasal curcumin administration was most appropriate in
reducing inflammation and oxidative stress and possesses therapeutic potential
against allergic asthma. Present study may prove the possibility of development
of curcumin nasal drops towards treatment of allergic asthma.
PMID- 29959625
TI - Spilanthol Inhibits COX-2 and ICAM-1 Expression via Suppression of NF-kappaB and
MAPK Signaling in Interleukin-1beta-Stimulated Human Lung Epithelial Cells.
AB - Spilanthol a phytochemical derived from the Spilanthes acmella plant has
antimicrobial, antioxidant, and anti-inflammatory properties. This study
evaluated its effects on the expression of intercellular adhesion molecule 1
(ICAM-1) and inflammation-related mediators in IL-1beta-stimulated human lung
epithelial A549 cells. Human lung epithelial A549 cells were pretreated with
various concentrations of spilanthol (3-100 MUM) followed by treatment with IL
1beta to induce inflammation. The protein levels of pro-inflammatory cytokines,
chemokines, and prostaglandin E2 (PGE2) were measured using ELISA. Cyclooxygenase
2 (COX-2), heme oxygenase (HO-1), nuclear transcription factor kappa-B (NF
kappaB), and mitogen-activated protein kinase (MAPK) were measured by
immunoblotting. The mRNA expression levels of ICAM-1 and MUC5AC were determined
by real-time polymerase chain reaction. Spilanthol decreased the expression of
PGE2, COX-2, TNF-alpha, and MCP-1. It also decreased ICAM-1 expression and
suppressed monocyte adhesion to IL-1beta-stimulated A549 cells. Spilanthol also
significantly inhibited the phosphorylation of MAPK and I-kappaB. These results
suggest that spilanthol exerts anti-inflammatory effects by inhibiting the
expression of the pro-inflammatory cytokines, COX-2, and ICAM-1 by inhibiting the
NF-kappaB and MAPK signaling pathways. Graphical Abstract ?.
PMID- 29959626
TI - Mitophagy Contributes to the Pathogenesis of Inflammatory Diseases.
AB - Mitophagy is a metabolic process to remove excessive or damaged mitochondria in
eukaryotic cells. It is well-known that mitochondria are one of the major sources
of reactive oxygen species (ROS). Mitochondrial ROS and damage-associated
molecular patterns (DAMPs) can activate inflammasomes to induce inflammatory
responses. Once the activation is regulated improperly, excessive inflammation
will bring about various tissue injuries, resulting in a series of diseases.
However, the selective mitochondrial autophagy can specifically eliminate
dysfunctional mitochondria to maintain mitochondrial homeostasis and protect
against the hyperinflammation induced by ROS and DAMPs. Recent studies
demonstrated that a variety of internal and external factors regulate several
inflammatory diseases via altering the level of mitophagy. In this review, we
summarize the latest research progress of mitophagy and focus on the inflammatory
responses regulated by mitophagy, aiming to illuminate the role of mitophagy in
inflammation and provide clues to the diagnosis and therapy of inflammatory
diseases.
PMID- 29959627
TI - CIDEC Is Involved in LPS-Induced Inflammation and Apoptosis in Renal Tubular
Epithelial Cells.
AB - Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been shown to have
anti-inflammatory effect by inhibition of the nuclear factor kappaB (NF-kappaB)
pathway and is involved in lipopolysaccharide (LPS)-induced inflammation. Cell
death-inducing DFF45-like effector C (CIDEC) can directly down-regulate AMPK
activity through interacting with AMPKalpha subunit. However, whether the AMPK or
CIDEC is involved in LPS-induced inflammation in renal tubular epithelial cells
is still unknown. Therefore, we studied the role of AMPK and CIDEC in LPS-treated
NRK-52E cells. Our results showed that LPS could up-regulate the expression of
CIDEC in vitro and in vivo. Silencing CIDEC by CIDEC-siRNA could restore
expression of phosphorylated-AMPKalpha which was decreased by LPS, suppress LPS
induced NF-kappaB pathway activation, and TNF-alpha, IL-6, and IL-1beta
production in NRK-52E cells. Furthermore, silencing CIDEC also partially
alleviated LPS-induced epithelial cells apoptosis. In conclusion, the results
demonstrated that CIDEC/AMPK signaling pathway played an important role in LPS
induced inflammation and epithelial cells apoptosis.
PMID- 29959628
TI - Insights into the interaction and binding mode of a set of antifungal azoles as
inhibitors of potential fungal enzyme-based targets.
AB - Azole-containing compounds are a kind of chemical entities of natural and
synthetic origin having a wide-range of activities. They are therefore considered
as important moieties for fungicide development, mostly due to the possible
action on several enzyme-based targets. As part of our research on fungicidal
agents, the relationship between the ligand-enzyme affinities of several
synthetic azole-containing compounds against a set of fungal enzyme-based targets
was in silico evaluated through molecular docking. The affinity values of the
test compounds were mostly higher than those of the respective test controls.
Binding modes between enzymes and test compounds were firstly investigated
through Vina scores and ligand-residue interactions. Furthermore, statistically
relationships among docking scores were successfully found by multivariate
analysis. They were mostly correlated with reported MIC80 values, so it denoted
an evident discrimination of the test compounds. Strong electron withdrawing
groups on phenylacrylamide moiety were responsible for establishing stronger
complexes with the enzyme targets, being trichodiene synthase and alpha-L
fucosidase the most important ones. Moreover, stability of a set of
representative protein/ligand complexes was also analyzed by 10 ns molecular
dynamics simulations (MD). Significant differences into the MD runs were detected
and directly correlated to docking performances. Finally, docking affinity scores
and HOMO-LUMO energy gaps resulted well predicted by comparative molecular field
analysis (CoMFA) models, demonstrating the structure type is particularly
associated with those calculated properties and these results were thus
consistent with the respective validation parameters.
PMID- 29959629
TI - Photoelectrochemical aptasensor for sulfadimethoxine using g-C3N4 quantum dots
modified with reduced graphene oxide.
AB - A novel photoelectrochemical (PEC) aptasensor with graphitic-phase carbon nitride
quantum dots (g-C3N4; QDs) and reduced graphene oxide (rGO) was fabricated. The g
C3N4 QDs possess enhanced emission quantum yield (with an emission peak at 450
nm), improved charge separation ability and effective optical absorption, while
rGO has excellent electron transfer capability. Altogether, this results in
improved PEC performance. The method is making use of an aptamer against
sulfadimethoxine (SDM) that was immobilized on electrode through pi stacking
interaction. Changes of the photocurrent occur because SDM as a photogenerated
hole acceptor can further accelerate the separation of photoexcited carriers.
Under optimized conditions and at an applied potential of +0.2 V, the aptasensor
has a linear response in the 0.5 nM to 80 nM SDM concentration range, with a 0.1
nM detection limit (at S/N = 3). The method was successfully applied to the
analysis of SDM in tap, lake and waste water samples. Graphical abstract
Graphitic-phase carbon nitride (g-C3N4) quantum dots (QDs) and reduced graphene
oxide (rGO) were used to modify fluorine-doped SnO2 (FTO) electrodes for use in a
photoelectrochemical (PEC) aptasensor. SDM oxidized by the hole on valance band
(VB) of g-C3N4 QDs promote the separation of electron in the conductive band
(CB), which made the changes of photocurrent signal.
PMID- 29959631
TI - Argon laser-assisted hypotony model in the rabbit.
AB - To investigate whether ocular hypotony formation with 360 degrees
endocyclophotocoagulation is possible. Twelve male New Zealand White rabbits were
used. Entire ciliary body epithelium was destructed with green laser
photocoagulation after pars plana lensectomy and anterior vitrectomy in six
rabbits. Endocyclophotocoagulation was not performed to the remaining six rabbits
(control group). Intraocular pressure (IOP) was measured preoperatively and
followed up everyday in the first week and weekly until the end of month one. All
of the rabbits were sacrificed and ciliary bodies were left for gross and light
microscopic examination. Mean baseline IOPs were similar in laser and non-laser
group (14.8 +/- 1.4 (range 12.2-17.3) vs 14.4 +/- 1.4 (range 12.2-15.9), p =
0.650). Mean IOP was 6.6 +/- 0.45 mmHg (range 5.9-7.1) in the laser group and
11.5 +/- 1.2 mmHg (range 10.2-13.4) in the non-laser group in postoperative day
1. IOP was below 4 mmHg in all eyes on the second day and after in laser group.
In the macroscopic evaluation, the entire ciliary body had a white (loss of
pigmentation) and atrophic appearance in all of the eyes in the laser-treated
group compared to non-laser group. In the laser group, light microscopic
examination demonstrated a severe 360 degrees disruption of ciliary processes.
Ciliary processes were covered with fibrin exudation consisting of fibroblasts.
There was a mild inflammation with disruption or atrophy of ciliary body
epithelium with cystic vacuolar degeneration. Three hundred sixty degrees
endocyclophotocoagulation yielded severe ciliary epithelium damage. IOP reduction
started very early and continued in hypotonic levels during follow up period.
PMID- 29959630
TI - Population-Based Analysis of Cluster Headache-Associated Genetic Polymorphisms.
AB - Cluster headache is a disorder with increased hereditary risk. Associations
between cluster headache and polymorphism rs2653349 of the HCRTR2 gene have been
demonstrated. The less common allele (A) seems to reduce disease susceptibility.
The polymorphism rs5443 of the GNB3 gene positively influences triptan treatment
response. Carriers of the mutated T allele are more likely to respond positively
compared to C:C homozygotes, when treated with triptans. DNA was extracted from
buccal swabs obtained from 636 non-related Southeastern European Caucasian
individuals and was analyzed by real-time PCR. Gene distribution for the
rs2653349 was G:G = 79.1%, G:A = 19.2%, and A:A = 1.7%. The frequency of the wild
type G allele was 88.7%. The frequencies for rs5443 were C:C = 44.0%, C:T =
42.6%, and T:T = 13.4%. The frequency of the wild-type C allele was 65.3%. The
frequency distribution of rs2653349 in the Southeastern European Caucasian
population differs significantly when compared with other European and East Asian
populations, and the frequency distribution of rs5443 showed a statistically
significant difference between Southeastern European Caucasian and African, South
Asian, and East Asian populations. For rs2653349, a marginal statistically
significant difference between genders was found (p = 0.080) for A:A versus G:G
and G:A genotypes (OR = 2.78), indicating a higher representation of male
homozygotes for the protective mutant A:A allele than female. No statistically
significant difference was observed between genders for rs5443. Cluster headache
pathophysiology and pharmacotherapy response may be affected by genetic factors,
indicating the significant role of genotyping in the overall treatment
effectiveness of cluster headaches.
PMID- 29959632
TI - Appropriate laser wavelengths for photodynamic therapy with methylene blue.
PMID- 29959633
TI - Comparative study of photodynamic activity of methylene blue in the presence of
salicylic acid and curcumin phenolic compounds on human breast cancer.
AB - Curcumin and salicylic acid are both phenolic compounds and they can both affect
cancer treatment efficacy. In this study, the effects of methylene blue-curcumin
(CU-MB) and methylene blue-salicylic acid (SA-MB) ion pair complexes on MDA-MB
231 human breast cancer cells are studied. According to the thermodynamic
parameters, the stability of curcumin and salicylic acid complexes ion pair
complexes was compared. The free energy of ion pair interactions was calculated
based on binding constants. A comparison of the free energies of the complexes
(CU-MB: ?G degrees b1 = - 21.11 kJ/mol and ?G degrees b2 = - 8.37 kJ/mol, SA-MB:
?G degrees b1 = - 12.92 kJ/mol and ?G degrees b2 = - 9.02 kJ/mol) indicates that
the interaction of methylene blue in first binding interaction with curcumin is
greater than that of methylene blue with salicylic acid. Electrostatic
interactions are the main forces in the binding of both compounds to methylene
blue. All forces are inter-molecular physical interactions. The results of
cellular experiments show that ion pairing has enhanced the reduction of cell
viability. By increasing molecular stability and prevention of dimerization of
methylene blue, the cell killing potential of methylene blue increases and it
subsequently causes enhancement of photodynamic efficacy.
PMID- 29959634
TI - Prognostic significance of high serum p53 antibody titers in patients with
esophageal squamous cell carcinoma.
AB - BACKGROUND: The p53 protein overexpression that usually results from genetic
alterations reportedly induces serum antibodies against p53. However, little
information is available about the prognostic significance of perioperative serum
p53 antibody (s-p53-Abs) titers in patients with esophageal squamous cell
carcinoma. METHODS: In this study, we retrospectively evaluated the clinical
significance of perioperative s-p53-Abs in 135 patients with esophageal squamous
cell carcinoma. Of these, 58 patients received neoadjuvant chemotherapy
comprising 5-FU and CDDP. While the cutoff level at 1.3 U/ml indicated
seropositive patients, level of 13.4 U/ml was used to identify high-titer
patients. We monitored serum titers seropositive patients after surgery and
evaluated the prognostic significance by the univariate and multivariate
analyses. RESULTS: In this study, 29 patients (21.5%) were positive for s-p53-Abs
before treatment. The frequency of both seropositive patients and high-titer
patients (> 13.4 U/ml) was not significantly associated with tumor progression.
While seropositive patients did not demonstrate significant poor overall
survival, high-titer patients demonstrated significant poor overall survival
based on the multivariate analysis (P < 0.001). Moreover, the s-p53-Abs titer did
not correlate with the response to neoadjuvant chemotherapy. Among seropositive
patients, the negative conversion of s-p53-Abs more likely led to be long-term
survival. CONCLUSIONS: This study determined that the high-titer of s-p53-Abs was
an independent risk factor to reduce the overall survival of patients with
esophageal cancer patients. The negative conversion of s-p53-Abs could be a good
indicator of favorable prognosis.
PMID- 29959635
TI - Association between insomnia and job stress: a meta-analysis.
AB - PURPOSE: Insomnia has become one of the foremost health concerns among workers.
Despite a significant number of epidemiological studies have reported on the
correlation between insomnia and job stress, comprehensive evidence remains
insufficient. Therefore, this research seeks to provide evidence with greater
reliability, through summarizing relevant contemporary literature via a meta
analysis. METHODS: Literature from across Europe and Asia that was of both a
prospective and cross-sectional design was included, if well-controlled odds
ratios were available. The meta-analysis was undertaken in accordance with the
guidelines devised by PRISMA, including tests for publication bias and
heterogeneity. RESULTS: High job stress was associated with a greater risk of
suffering from insomnia (random OR = 1.73, 95% CI 1.46-2.05), and the correlation
between effort-reward imbalance and insomnia was statistically significant
(random OR = 2.63, 95% CI 1.22-5.69). Higher demand was correlated to a
relatively greater risk of insomnia (random OR = 1.35, 95% CI 1.20-1.51), while
the pooled effect of low control was not found to be statistically significant.
The summary random odds ratio of heavy workload was 2.76, and a pooled odds ratio
of 1.67 (fixed, 95% CI 1.11-2.52) was calculated in low social support. With
regard to the overall population, work-family conflict was correlated with
insomnia (random OR = 2.32, 95% CI 1.53-3.51). The subgroup analysis provided
comparable outcomes, for both males (fixed OR = 1.97, 95% CI 1.50-2.57) and
females (random OR = 2.80, 95% CI 1.30-6.05). Egger's regression indicated that
publication bias may be apparent in the syntheses of effort-reward imbalance, low
social support, and work-family conflict (p < 0.05). Heterogeneity was caused by
design, measuring the exposure or outcome, in addition to the region where the
research was conducted. CONCLUSIONS: The correlation between insomnia and higher
levels of job stress, effort-reward imbalance, high demand, heavy workload, and
low social support was determined. Publication bias and heterogeneity were
partially observed. Furthermore, future studies with improved methodologies and a
focus on mechanisms are anticipated.
PMID- 29959636
TI - Comparison of Ki-67 labeling index measurements using digital image analysis and
scoring by pathologists.
AB - BACKGROUND: Routine analysis of Ki-67 is not widely recommended for clinical
decision-making because of poor reproducibility. Furthermore, counting numerous
cells can be laborious for pathologists. Digital image analysis for
immunohistochemical analysis was recently developed; however, the clinical
efficacy of the Ki-67 index obtained using image analysis is unknown. METHODS: We
retrospectively identified female patients with breast cancer with
immunohistochemical Ki-67 and survival data using the pathology database at the
Tokai University, Japan. Ki-67 expression was scored by three pathologists.
Slides were scanned and converted to virtual slides; Ki-67-positive cells were
counted using image analysis. Ki-67 indices obtained by the pathologist's scoring
and image analysis were evaluated by 2 * 2 analysis. Relationships between Ki-67
index and survival outcomes were evaluated using the Kaplan-Meier method and
compared using the log-rank test. RESULTS: Based on the 2 * 2 analysis, Ki-67
index obtained using image analysis was moderately correlated with the
pathologist's scoring for all patients (kappa 0.41; sensitivity, 0.573;
specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67
index than with low Ki-67 index for estrogen receptor-positive, human epidermal
growth factor receptor 2-negative, and stage I or II patients scored by
pathologists (p < 0.001) and obtained using image analysis (p = 0.031).
CONCLUSIONS: The Ki-67 indices obtained using image analysis were moderately
correlated with those scored by pathologists. Digital image analysis can be
effective for measuring Ki-67 values, because they are associated with relapse
free survival in estrogen receptor-positive, human epidermal growth factor
receptor 2-negative, and patients at stage I or II.
PMID- 29959637
TI - Isolation and Partial Characterization of Lactic Acid Bacteria from the Gut
Microbiota of Marine Fishes for Potential Application as Probiotics in
Aquaculture.
AB - With the increase of antimicrobial resistances due to the widespread use of
antibiotics, the search of new probiotics to control aquaculture diseases has a
growing public interest. The aim of this study was to isolate bacteria with
antimicrobial effect from the gut of marine healthy fishes and select lactic acid
bacteria (LAB) as potential probiotics, being strains considered as generally
regarded as safe (GRAS) by the European Food Safety Agency (EFSA). Of a total of
45 Gram-positive strains with antimicrobial activity found in a screening of the
gut microbiota of 13 marine fishes, nine were identified as LAB by 16S rRNA gene
sequencing. LAB strains (five Lactococcus lactis subsp. lactis, two Enterococcus
spp., one Lactobacillus plantarum, and one Leuconostoc mesenteroides subsp.
mesenteroides) also showed a broad-spectrum antibacterial activity against
aquaculture pathogens such as Vibrio harveyi, V. splendidus, and Photobacterium
damselae and survived in experimental gastrointestinal conditions when grown in
culture media modified with different values of pH and bile salts. These results
showed the potential of LAB obtained from the indigenous microbiota of wild
marine fishes for use as probiotics in aquaculture.
PMID- 29959638
TI - Anatomical evaluation of intracranial aneurysm rupture risk in patients with
multiple aneurysms.
AB - In patients with aneurysmal subarachnoid hemorrhage (aSAH) and multiple
aneurysms, there is a need to objectively identify the ruptured aneurysm.
Additionally, studying the intra-individual rupture risk of multiple aneurysms
eliminates extrinsic risk factors and allows a focus on anatomical factors, which
could be extrapolated to patients with single aneurysms too. Retrospective bi
center study (Department of Neurosurgery of the University Hospital Duesseldorf
and Bern) on patients with multiple aneurysms and subarachnoid hemorrhage caused
by the rupture of one of them. Parameters investigated were height, width, neck,
shape, inflow angle, diameter of the proximal and distal arteries, width/neck
ratio, height/width ratio, height/neck ratio, and localization. Statistical
analysis and logistic regressions were performed by the R program, version 3.4.3.
N = 186 patients with aSAH and multiple aneurysms were treated in either
department from 2008 to 2016 (Bern: 2008-2016, 725 patients and 100 multiple
aneurysms, Duesseldorf: 2012-2016, 355 patients, 86 multiple aneurysms). The mean
age was 57 years. N = 119 patients had 2 aneurysms, N = 52 patients had 3
aneurysms, N = 14 had 4 aneurysms and N = 1 had 5 aneurysms. Eighty-four percent
of ruptured aneurysms were significantly larger than the largest unruptured.
Multilobularity of ruptured aneurysms was significantly higher than in
unruptured. Metric variables describing the geometry (height, width, etc.) and
shape are the most predictive for rupture. One or two of them alone are already
reliable predictors. Ratios are completely redundant in saccular aneurysms.
PMID- 29959639
TI - Remission of aggressive autoimmune disease (dermatomyositis) with removal of
infective jaw pathology and ozone therapy: review and case report.
AB - INTRODUCTION: This case uniquely reports a connection between endodontically
infected teeth and systemic disease, and additionally presents ozone therapy as a
unique therapy and immune system modulator. It is the world's first such reported
case and the treatment holds invaluable lessons in assessing the "unknown" causes
of autoimmunity and inflammation. Additionally, it presents ozone therapy as a
most needed unique, non-toxic and powerful anti-infective agent, anti
inflammatory and immune modulator. CASE PRESENTATION: The patient was a Mexican
male field laborer, age 48 years, in inflammatory crisis with a confirmed case of
dermatomyositis. He had received massive prednisone, and powerful immune
suppressing drugs just to function, while disease still raged. I encountered him
in the field in June 2012 with severe muscle pain, weakness, and diffuse
generalized skin rash, essentially unable to do his work. Creatine kinase peaked
at 9293 U/L. History and physical examination findings caused suspicion of
subclinical infections in endodontically treated teeth. This impression was
confirmed in subsequent dental evaluation. He fully recovered after dental
infections were confirmed and surgically removed, while receiving ozone therapy
until all symptoms and laboratory abnormalities normalized. CONCLUSION: Dental
focus of occult infection may be a prime cause/trigger of autoimmune disorders
and inflammatory disorders, requiring surgical intervention to remove. Ozone
therapy, little known in conventional medicine, has been shown in the literature
and in this case to be a powerful and safe immune modulator and anti-infective
agent. This case has significant relevance across the entire spectrum of both
medical and dental practice. It also emphasizes the need for individualized
assessment and treatment rather than symptomatic pharmacological approaches
treating a "disease" rather than the patient. Subclinical dental infection and
ozone therapy are reviewed.
PMID- 29959640
TI - Obstructed Paraduodenal Hernia.
PMID- 29959641
TI - Disseminated Peritoneal Leiomyomatosis.
PMID- 29959642
TI - Giant Primary Retroperitoneal Dedifferentiated Liposarcoma.
PMID- 29959643
TI - Anterior Approach to Major Resection for Colorectal Liver Metastasis.
AB - PURPOSE: The aim of this study was to examine the merits of the anterior
approach, if any, in colorectal liver metastasis (CRLM) resection. METHODS: Data
of patients who underwent partial hepatectomy for CRLM were reviewed. Patients
treated by the anterior approach were compared with patients treated by the
conventional approach. RESULTS: Ninety-eight patients had right hepatectomy,
extended right hepatectomy, or right trisectionectomy. Among them, 71 patients
underwent the conventional approach (CA group) and 27 underwent the anterior
approach (AA group). The two groups were comparable in demographic, pathological,
and perioperative characteristics except that the AA group had higher levels of
aspartate transaminase (median, 41 vs. 31 U/L; p = 0.006) and alanine
transaminase (median, 27 vs. 22 U/L; p = 0.009), larger tumors (median, 7 vs. 4
cm; p = 0.000), and more extensive resections (p < 0.001). The median overall
survival was 40 months (range, 0.69-168.6 months) in the CA group and 33.7 months
(range, 0.95-99.8 months) in the AA group (p = 0.22), and the median disease-free
survival was 9.7 months (range, 0.62-168.6 months) in the CA group and 6.2 months
(range, 0.72-99.8 months) in the AA group (p = 0.464). Univariate and
multivariate analyses identified 4 independent prognostic factors for overall
survival: lymph node status of primary tumor (HR 1.352, 95% CI 0.639-2.862, p =
0.034), intraoperative blood loss (HR 1.253, 95% CI 1.039-1.510, p = 0.018),
multiple liver tumor nodules (HR 1.775, 95% CI 1.029-3.061, p = 0.039), and
microvascular invasion (HR 2.058, 95% CI 1.053-4.024, p = 0.035). CONCLUSIONS:
The two approaches resulted in comparable survival outcomes even though the AA
group had larger tumors and more extensive resections. The anterior approach
allows better mobilization and easier removal of large tumors once the liver is
opened up.
PMID- 29959644
TI - Correction to: Intrinsic and inducible resistance to hydrogen peroxide in
Bifidobacterium species.
AB - In the published article, the co-author Abdelmoneim Abdalla's affiliation has
been published incompletely. The additional affiliation is given below.
PMID- 29959645
TI - Is There Any Role of Arsenic Toxicity in HPV Related Oral Squamous Cell
Carcinoma?
AB - Arsenic is a potent human carcinogen affecting the rate of cancer deaths
worldwide. In India, West Bengal is the worst affected state by arsenic. To our
best knowledge, this is the first study relating arsenic toxicity with oral
carcinoma, along with HPV infection, the latter being well established in western
countries. To find out a possible correlation between arsenic toxicity and oral
carcinoma in the population of West Bengal, in or without any association with
human papilloma virus infection. Ethical clearance of this study was obtained
from the institutional committee. One hundred and four malignant and 103
premalignant cases were selected for this study along with 200 healthy age and
sex-matched individuals selected as control (100 each for malignant and
premalignant) (2013-2017). On proper consent, their buccal swab and hair samples
were assessed for the presence of HPV DNA by DNA extraction, followed by PCR and
arsenic estimation by flow injection hydride generation atomic absorption
spectrometry respectively. A very highly significant correlation has been
observed between arsenic toxicity, HPV infection and the occurrence of oral
carcinoma (p value = 2.18e-06; p value = 0.00100 respectively). A correlation has
also been observed between these two factors simultaneously, contributing to this
malignancy (phi coefficient = 0.2194839). A statistically significant correlation
observed between this metal toxicity and viral infection in the occurrence of
oral carcinoma in this population indicates a possible symbiotic role between
these two factors in this malignancy.
PMID- 29959646
TI - Assessment of the Health Risk Induced by Accumulated Heavy Metals from Anaerobic
Digestion of Biological Sludge of the Lettuce.
AB - Heavy metals are a group of pollutants in biological sludge. Many agencies
regulated guidelines for heavy metal concentrations for various applications of
sludge such as agricultural application. In this study, we tried to determine
heavy metal fate after anaerobic digestion. Additionally, we determined the
bioaccumulation rate of heavy metals in lettuce cultivated on a sludge-applied
land. Heavy metal (As, Pb, Hg, Cd) contents of solid and liquid parts of raw and
anaerobically digested sludge were separately measured by ICP-OES. For this
purpose, the samples were digested using nitric acid, hydrochloric acid, and
boric acid. Then, the raw and anaerobically digested sludge were used for
cultivation of lettuce in separate farms. The heavy metal concentrations in the
harvested lettuce were measured by the same procedure. The results showed that
the main part of heavy metals in the raw sludge was in the liquid part (67%),
while, the main part of heavy metals in the anaerobically digested samples was in
the solid part of the sludge. Because of washout of dissolved heavy metals in the
liquid part of the sludge, the lettuce cultivated by anaerobically digested
sludge had higher content of the heavy metals in comparison to that of the
lettuce cultivated by the raw sludge. This study showed that application of
anaerobically digested sludge can increase the bioaccumulation rate of heavy
metals in the crops and induce more human health risk.
PMID- 29959647
TI - Human Sperm Characteristics with Regard to Cobalt, Chromium, and Lead in Semen
and Activity of Catalase in Seminal Plasma.
AB - We analyzed cobalt (Co), chromium (Cr), and lead (Pb) concentrations in human
semen and catalase CAT activity in seminal plasma and the effects of their
relations on the sperm quality. We obtained semen samples from men (n = 168)
undergoing routine infertility evaluation. Studies included two groups based on
the ejaculate parameters: I (n = 39; normal ejaculate; normozoospermia); II (n =
129; pathological spermiogram). We examined relationships and differences between
Co, Cr, and Pb concentrations in seminal plasma, CAT activity, and semen
parameters. We did not establish differences in Co, Cr, and Pb concentrations and
CAT activity from men between normozoospermic and those with pathological
spermiogram. We found a significantly lower Co concentration and CAT activity in
males with normal sperm motility than in asthenozoospermic males. We found
significantly lower Co and a higher Pb concentration in males with normal
morphology of spermatozoa than in teratozoospermic males. We found a
significantly higher Pb concentration in the individuals with consumption of
alcohol than in those without consumption. There were significant correlations
between Co and Pb concentrations, sperm progressive motility (A + B, i.e., fast
and slow progressive motility; Co-negatively; Pb-positively), and normal
morphology of spermatozoa (Co-negatively; Pb-positively). We found a significant
negative correlation between Cr concentration and slow progressive motility, and
between CAT activity and volume of ejaculate. Co, Cr, and Pb levels and CAT
activity were related to sperm characteristics and male fertility. The impact of
alcohol may be manifested by a disturbance in Pb equilibrium in the body. Co and
Pb influence progressive motility and normal morphology of human spermatozoa.
Thus, Co and Pb levels in semen may be a useful diagnostic in male infertility.
Most of the results of this study are in contrast to expectations. Namely, Pb is
a toxic element and its harmful effects (poor semen quality) may be expected
already at relatively low level of Pb exposure and are particularly visible with
increasing of Pb. Co and Cr(III) are essential elements and harmful effects may
be expected at their deficiency and/or overexposure.
PMID- 29959648
TI - Withdrawal from spinal application of remifentanil induces long-term potentiation
of c-fiber-evoked field potentials by activation of Src family kinases in spinal
microglia.
AB - It is well known that remifentanil, a widely used intravenous anesthesia drug,
can paradoxically induce hyperalgesia. The underlying mechanisms are still not
clear despite the wide investigations. The present study demonstrated that
withdrawal from spinal application of remifentanil could dose-dependently induce
long term potentiation (LTP) of C-fiber evoked field potentials. Remifentanil
withdrawal could activate Src family kinases (SFKs) in microglia, and upregulate
the expression of tumor necrosis factor alpha (TNFalpha) in spinal dorsal horn.
Furthermore, pretreatment with either microglia inhibitor Minocycline, SFKs
inhibitor PP2 or TNF alphaneutralization antibody could block remifentanil
withdrawal induced spinal LTP, whereas supplement of recombinant rat TNFalpha to
the spinal cord could reverse the inhibitory effect of Minocycline or PP2 on
remifentanil withdrawal induced LTP. Our results suggested that TNFalpharelease
following SFKs activation in microglia is involved in the induction of LTP
induced by remifentanil withdrawal.
PMID- 29959650
TI - Metronidazole-associated encephalopathy: a reversible condition.
PMID- 29959649
TI - eHealth to Enhance Treatment Adherence Among Youth Living with HIV.
AB - PURPOSE OF REVIEW: Multiple reviews have examined eHealth/mHealth interventions
to address treatment adherence, including those focusing on youth living with HIV
(YLWH). This review synthesizes results of prior reviews and recent studies (last
5 years) to provide a path forward for future research, acknowledging both
lessons learned and gaps to be addressed. RECENT FINDINGS: Recent studies provide
further evidence for the feasibility and acceptability of technology-based HIV
interventions. Formative research of more comprehensive smartphone applications
and pilot studies of computer-delivered interventions provide additional guidance
on YLWH's preferences for intervention components and show promising preliminary
efficacy for impacting treatment adherence. Expanding access to technology among
YLWH, in the United States (US) and globally, supports the continued focus on
eHealth/mHealth interventions as a means to reduce disparities in clinical
outcomes. Future research should lend greater focus to implementation and scale
up of interventions through the use of adaptive treatment strategies that include
costing analyses, measuring and maximizing engagement, fostering information
sharing between researchers, and building upon sustainable platforms.
PMID- 29959651
TI - Inorganic mercury in human astrocytes, oligodendrocytes, corticomotoneurons and
the locus ceruleus: implications for multiple sclerosis, neurodegenerative
disorders and gliomas.
AB - Neurotoxic metals have been implicated in the pathogenesis of multiple sclerosis,
neurodegenerative disorders and brain tumours but studies of the location of
heavy metals in human brains are rare. In a man who injected himself with
metallic mercury the cellular location of mercury in his brain was studied after
5 months of continuous exposure to inorganic mercury arising from metallic
mercury deposits in his organs. Paraffin sections from the primary motor and
sensory cortices and the locus ceruleus in the pons were stained with
autometallography to detect inorganic mercury and combined with glial fibrillary
acidic protein immunohistochemistry to identify astrocytes. Inorganic mercury was
found in grey matter subpial, interlaminar, protoplasmic and varicose astrocytes,
white matter fibrous astrocytes, grey but not white matter oligodendrocytes,
corticomotoneurons and some locus ceruleus neurons. In summary, inorganic mercury
is taken up by five types of human brain astrocytes, as well as by cortical
oligodendrocytes, corticomotoneurons and locus ceruleus neurons. Mercury can
induce oxidative stress, stimulate autoimmunity and damage DNA, mitochondria and
lipid membranes, so its location in these CNS cells suggests it could play a role
in the pathogenesis of multiple sclerosis, neurodegenerative conditions such as
Alzheimer's disease and amyotrophic lateral sclerosis, and glial tumours.
PMID- 29959652
TI - Differences in Self-Reported Health and Unmet Health Needs Between Government
Assisted and Privately Sponsored Syrian Refugees: A Cross-Sectional Survey.
AB - Between November 2015 and January 2017, the Government of Canada resettled over
40,000 Syrian refugees through different sponsorship programs (GAR and PSR).
Timely access to healthcare is essential for good health and successful
integration. However, refugee support differs depending on sponsorship program,
which may lead to differences in healthcare service access and needs. A cross
sectional study with a sample of Syrian refugees was conducted to assess
healthcare access, and perceived physical and mental health status. Results
indicate demographic and healthcare access differences between GARs and PSRs.
GARs reported significantly lower perceived physical and mental health, as well
as, higher unmet healthcare needs than PSRs. GARs are among the most vulnerable
refugees; they report higher needs, more complex medical conditions and tend to
have more difficulty re-settling. These factors likely combine to help explain
lower self-reported health and higher health needs in our sample compared to
PSRs.
PMID- 29959654
TI - Correction to: Speculative Fiction and the Political Economy of Healthcare: Chang
Rae Lee's On Such a Full Sea.
AB - Due to an editing error, this article was initially published with an incorrect
title. The correct title is reflected above. The original article has been
corrected.
PMID- 29959653
TI - Comparison of Single-Session Dose Response Effects of Whole Body Vibration on
Spasticity and Walking Speed in Persons with Spinal Cord Injury.
AB - : Spasticity affects approximately 65% of persons with spinal cord injury (SCI)
and negatively impacts function and quality of life. Whole body vibration (WBV)
appears to reduce spasticity and improve walking function; however, the optimal
dose (frequency/duration) is not known. We compared single-session effects of
four different WBV frequency/duration dose conditions on spasticity and walking
speed, in preparation for a planned multi-session study. Thirty-five participants
with motor-incomplete SCI received four different doses of WBV: high frequency
(50 Hz)/short duration (180 s), high frequency/long duration (360 s), low
frequency (30 Hz)/short duration, and low frequency/long duration, plus a control
intervention consisting of sham electrical stimulation. In all conditions,
participants stood on the WBV platform for 45-s bouts with 1 min rest between
bouts until the requisite duration was achieved. The frequency/duration dose
order was randomized across participants; sessions were separated by at least 1
week. Quadriceps spasticity was measured using the pendulum test at four time
points during each session: before, immediately after, 15 min after, and 45 min
after WBV. Walking speed was quantified using the 10-m walk test at three time
points during each session: baseline, immediately after, and 45 min after WBV. In
the full group analysis, no frequency/duration combination was significantly
different from the sham-control condition. In participants with more severe
spasticity, a greater reduction in stretch reflex excitability was associated
with the high frequency/long duration WBV condition. The sham-control condition
was associated with effects, indicating that the activity of repeated sitting and
standing may have a beneficial influence on spasticity. TRIAL REGISTRATION:
NCT02340910 (assigned 01/19/2015).
PMID- 29959655
TI - Versatile catechol dioxygenases in Sphingobium scionense WP01T.
AB - The objective was to understand the roles of multiple catechol dioxygenases in
the type strain Sphingobium scionense WP01T (Liang and Lloyd-Jones in Int J Syst
Evol Microbiol 60:413-416, 2010a) that was isolated from severely contaminated
sawmill soil. The dioxygenases were identified by sequencing, examined by
determining the substrate specificities of the recombinant enzymes, and by
quantifying gene expression following exposure to model priority pollutants.
Catechol dioxygenase genes encoding an extradiol xylE and two intradiol
dioxygenases catA and clcA that are highly similar to sequences described in
other sphingomonads are described in S. scionense WP01T. The distinct substrate
specificities determined for the recombinant enzymes confirm the annotated gene
functions and suggest different catabolic roles for each enzyme. The role of the
three enzymes was evaluated by analysis of enzyme activity in crude cell extracts
from cells grown on meta-toluate, benzoate, biphenyl, naphthalene and
phenanthrene which revealed the co-induction of each enzyme by different
substrates. This was corroborated by quantifying gene expression when cells were
induced by biphenyl, naphthalene and pentachlorophenol. It is concluded that the
ClcA and XylE enzymes are recruited in pathways that are involved in the
degradation of chlorinated aromatic compounds such as pentachlorophenol, the XylE
and ClcA enzymes will also play a role in degradation pathways that produce
alkylcatechols, while the three enzymes ClcA, XylE and CatA will be
simultaneously involved in pathways that generate catechol as a degradation
pathway intermediate.
PMID- 29959656
TI - The composite redesign of humanity's nature: a work in process.
PMID- 29959657
TI - Myeloid-derived suppressor cells (MDSC): an important partner in cellular/tissue
senescence.
AB - The aging process is associated with a low-grade chronic inflammation and the
accumulation of senescent cells into tissues. Diverse stresses can trigger
cellular senescence, a cell fate characterized by cell-cycle arrest and flat
morphology. Oncogenic signaling can also induce cellular senescence which has
been termed oncogene-induced senescence (OIS). Senescent cells display a pro
inflammatory phenotype which has been called the senescence-associated secretory
phenotype (SASP). The secretomes associated with SASP contain colony-stimulating
factors and chemokines which stimulate the generation of myeloid-derived
suppressor cells (MDSC) by enhancing myelopoiesis in bone marrow and spleen.
Enhanced myelopoiesis and increased level of MDSCs have been observed in bone
marrow, spleen, and blood in both tumor-bearing and aged mice. Immunosuppressive
MDSCs are recruited via chemotaxis into inflamed tissues where they proliferate
and consequently suppress acute inflammatory reactions by inhibiting the
functions of distinct components of innate and adaptive immunity. For instance,
MDSCs stimulate the activity of immunosuppressive regulatory T-cells (Tregs).
They also increase the expression of amino acid catabolizing enzymes and the
secretion of anti-inflammatory cytokines, e.g. IL-10 and TGF-beta, and reactive
oxygen species (ROS). On the other hand, the accumulation of MDSCs into tissues
exerts harmful effects in chronic pathological disorders, e.g. tumors and many
age-related diseases, since the immunosuppression induced by MDSCs impairs the
clearance of senescent and cancer cells and also disturbs the maintenance of
energy metabolism and tissue proteostasis. The co-operation between senescent
cells and immunosuppressive MDSCs regulates not only tumorigenesis and chronic
inflammatory disorders but it also might promote inflammaging during the aging
process.
PMID- 29959658
TI - Prevalence of, and risk factors for, hematogenous fungal endophthalmitis in
patients with Candida bloodstream infection.
AB - PURPOSE: Endogenous fungal endophthalmitis (EFE) is a severe consequence of
candidemia. The prevalence of, and risk factors for, EFE is not well studied.
METHODS: We retrospectively collected cases of patients with candidemia who had
undergone ophthalmological examination between April 2011 and March 2016 in five
regional hospitals. We conducted bivariate and multivariate analyses using
patients' age, gender, causative Candida species, diabetes status, corticosteroid
use, cancer status, neutropenia, intensive care unit admission, presence of
central venous catheter (CVC), presence of shock, prior antibiotic use, 30-day
mortality, and highest Sequential Organ Failure Assessment (SOFA) score. Data on
sustained positive blood culture, beta-D glucan, CVC removal, empirical
antifungal drug used, and time to appropriate antifungal therapy were also
collected if available. RESULTS: Of 174 patients with candidemia, 35 (20.1%) were
diagnosed with EFE, including 31 (17.8%) with chorioretinitis and 4 (2.3%) with
vitritis. Bivariate analysis (EFE group vs. non-EFE group) found that Candida
albicans candidemia (77.1 vs. 34.5%, P < 0.001), neutropenia (14.3 vs. 5.8%, P =
0.141), CVC placement (94.3 vs. 71.2%, P = 0.004), and the presence of shock
(28.6 vs. 16.5%, P = 0.145) were each higher in the EFE group. Multivariate
logistic regression analysis found C. albicans candidemia (adjusted odds ratio
6.48; [95% CI 2.63-15.95]) and CVC placement (7.55 [1.56-36.53]) to be
significant risk factors for EFE. CONCLUSIONS: Candida albicans is the most
common causative agent for Candida EFE. Patients with candidemia and CVC
placement should be closely monitored by ophthalmologists.
PMID- 29959659
TI - Fumaric acid: a possible new therapy for macular edema?
AB - INTRODUCTION: Causes of macular edema are multifactorial, but inflammation,
vascular factors and mechanical traction are of major importance. Therapeutic
options of macular edema depend on the underlying cause. Intravitreal
administration of inhibitors of vascular endothelial growth factor leads to
inhibition of retinal neovascularization and subsequent edema. OBJECTIVE: Fumaric
acid esters are successfully used in dermatology for years according to their
antiangiogenic and anti-inflammatory effects. RESULT: For the very first time, we
describe a successful therapeutic attempt for macular edema, controlled by
optical coherence tomography using fumaric acid esters followed up for 60 months.
PMID- 29959660
TI - Similar Pharmacokinetics of the Adalimumab (Humira(r)) Biosimilar BI 695501
Whether Administered via Subcutaneous Autoinjector or Prefilled Syringe
(VOLTAIRE(r)-AI and VOLTAIRE(r)-TAI): Phase 1, Randomized, Open-Label, Parallel
Group Trials.
AB - INTRODUCTION: BI 695501 has shown similar efficacy, safety, and immunogenicity to
the adalimumab reference product, Humira(r). We present two phase 1 studies
comparing the pharmacokinetics, safety, and immunogenicity of BI 695501 delivered
via autoinjector (AI) vs. prefilled syringe (PFS). METHODS: Both trials were
randomized, open-label, parallel-group studies undertaken in subjects aged >= 18
65 years. VOLTAIRE(r)-AI (NCT02606903) recruited healthy, Caucasian, male, non
athletic volunteers with BMI >= 18 to <= 30 kg/m2. VOLTAIRE(r)-TAI (NCT02899338)
recruited healthy men and women with BMI > 17.5 to < 35 kg/m2. In both studies, a
single dose of BI 695501 40 mg was administered via AI or PFS to the abdomen
(VOLTAIRE(r)-AI) or thigh (VOLTAIRE(r)-TAI). The observation period was 43/57
days and the safety follow-up was 70 days. Co-primary endpoints were AUC0-1032 or
AUC0-1368, Cmax, and AUC0-infinity. Safety and immunogenicity were assessed.
RESULTS: Subjects (VOLTAIRE(r)-AI: N = 71; VOLTAIRE(r)-TAI: N = 162) were
randomized to AI (n = 35; n = 81) or PFS (n = 36; n = 81). Baseline
characteristics were balanced between treatment groups in each study. Total
exposure of BI 695501 was similar for both groups; adjusted geometric mean ratios
for AUC0-infinity, AUC0-1032, and Cmax were 106.17, 104.09, and 114.83%,
respectively, for VOLTAIRE(r)-AI; 103.19, 101.71 (AUC0-1368), and 100.11% for
VOLTAIRE(r)-TAI. In both studies, similar immunogenicity was observed between
groups in terms of frequency of binding and neutralizing anti-drug antibody
positive subjects. Incidence of adverse events was similar for both groups.
CONCLUSIONS: Pharmacokinetics and immunogenicity of BI 695501 delivered via AI
were similar to administration using a PFS, independent of injection site. No
differences are expected between AI and PFS use in clinical practice. FUNDING:
Boehringer Ingelheim.
PMID- 29959661
TI - Offspring Personality Mediates the Association between Maternal Depression and
Childhood Psychopathology.
AB - Offspring of mothers diagnosed with major depression are at increased risk for a
wide range of psychological problems. Previous research has shown that individual
differences in personality development can be informative for predicting risk and
resilience to psychopathology, especially within at-risk populations. In the
present study, we examined whether individual differences in offspring
personality development during early to middle childhood could account for the
association between maternal depression and offspring behavior problems later in
childhood. Participants included 64 offspring of mothers diagnosed with major
depression and 68 offspring of healthy comparison mothers. Personality was
assessed via parent report at ages 3, 4, 5, and 9. Offspring internalizing and
externalizing symptoms were assessed at age 9 via parent and teacher report.
Results of latent growth curve models indicated that offspring Neuroticism,
Conscientiousness, and Agreeableness mediated the link between early maternal
depression and later childhood behavior problems, though results varied across
maternal and teacher reports. Findings suggest that individual differences in
youth personality and personality development are important predictors of
emerging psychopathology among offspring of mothers diagnosed with depression.
PMID- 29959662
TI - Auditory attention switching and judgment switching: Exploring multicomponent
task representations.
AB - An auditory attention-switching paradigm was combined with a judgment-switching
paradigm to examine the interaction of a varying auditory attention component and
a varying judgment component. Participants heard two dichotically presented
stimuli-one spoken by a female speaker and one spoken by a male speaker. In each
trial, the stimuli were a spoken letter and a spoken number. A visual explicit
cue at the beginning of each trial indicated the auditory attention criterion
(speaker sex/ear) to identify the target stimulus (Experiment 1) or the judgment
that had to be executed (Experiment 2). Hence, the attentional selection
criterion switched independently between speaker sexes (or between ears), while
the judgment alternated between letter categorization and number categorization.
The data indicate that auditory attention criterion and judgment were not
processed independently, regardless of whether the attention criterion or the
judgment was cued. The partial repetition benefits of the explicitly cued
component suggested a hierarchical organization of the auditory attention
component and the judgment component within the task set. We suggest that the
hierarchy arises due to the explicit cuing of one component rather than due to a
"natural" hierarchy of auditory attention component and judgment component.
PMID- 29959663
TI - Multiple attentional control settings at distinct locations without the
confounding of repetition priming.
AB - An attentional control setting (ACS), which is based on the task goal, induces
involuntary attentional capture by a stimulus possessing a target-defining
feature. It is unclear whether ACSs are maintained for multiple targets defined
as conjunctions of a color and location. In the present study we examined the
possibility of local ACSs for dual targets defined as combinations of color and
location, using different paradigms: visual search in Experiment 1, and spatial
cueing in Experiment 2. In Experiment 1, a distractor captured attention only
when its features matched the ACSs. Likewise, in Experiment 2, a significant
attentional capture effect was found only with a matching cue, whose color and
location were in line with the conjunction of the target definition. Importantly,
the identical pattern of attentional capture was also obtained for a neutral
color target, which was unlikely to be primed by any color of the cue. Thus,
these findings imply that the attentional bias depending on the match between the
cue and target did not result from cue-target repetition priming. The present
study highlights that top-down attentional control can be set flexibly to
accomplish a complex task goal efficiently.
PMID- 29959664
TI - Reflex Testing of Immunoglobulins in Patients with Total Serum IgE < 2 kU/L.
PMID- 29959665
TI - Spherical Nucleic Acid Nanoparticles: Therapeutic Potential.
AB - Spherical nucleic acids (SNAs) are highly oriented, well organized, polyvalent
structures of nucleic acids conjugated to hollow or solid core nanoparticles.
Because they can transfect many tissue and cell types without toxicity, induce
minimum immune response, and penetrate various biological barriers (such as the
skin, blood-brain barrier, and blood-tumor barrier), they have become versatile
tools for the delivery of nucleic acids, drugs, and proteins for various
therapeutic purposes. This article describes the unique structures and properties
of SNAs and discusses how these properties enable their application in gene
regulation, immunomodulation, and drug and protein delivery. It also summarizes
current efforts towards clinical translation of SNAs and provides an expert
opinion on remaining challenges to be addressed in the path forward to the
clinic.
PMID- 29959666
TI - Effects of 3 months of detraining on functional fitness and quality of life in
older adults who regularly exercise.
AB - BACKGROUND: Little is known about the effects of detraining in older adults,
particularly those who regularly exercise. AIMS: To determine the consequences of
3 months of cessation of a habitual supervised exercise on functional fitness and
quality of life in aged adults and to explore the associations among those
parameters. METHODS: Thirty-eight women and 11 men (mean age 75.5 +/- 5.7 years)
took part in a physical exercise program for 9 months, followed by a 3-month
detraining period. Participants completed physical function tests and
questionnaires regarding the quality of life and leisure-time physical activity
at the end of the exercise program (baseline) and 3 months later (detraining).
RESULTS: After the detraining period, performance in the 8 Foot Up and Go test (p
< 0.001) and the physical and mental components of the quality of life (p <
0.001) declined. Significant correlations were observed when comparing the 8 Foot
Up and Go test (p < 0.05), Chair Stand test (p < 0.05), and the 6-min Walk test
(p < 0.001) to the physical component of the quality of life after the detraining
period. CONCLUSION: Three months of a detraining period in older people who
habitually undertake supervised activities is enough to produce a decline in
dynamic balance and also quality of life. To avoid the deleterious effect of
periods of cessation of supervised exercise, as a suggestion, specifically
designed exercises could be prescribed for an older population, with emphasis on
balance exercises.
PMID- 29959667
TI - Diazepam as an oral hypnotic increases nocturnal blood pressure in the elderly.
AB - BACKGROUND: No study has evaluated the cardiovascular effects of diazepam in
elderly subjects that assume diazepam to induce sleep. PURPOSE: The present study
was carried out in order to evaluate the effects of chronic administration of
diazepam as hypnotic drug on blood pressure (BP) and heart rate (HR) in healthy
elderly subjects. PATIENTS AND METHODS: Healthy, elderly subjects, aged 65-74
years, were treated with diazepam 5 mg or placebo-both administered once a day in
the evening-for 4 weeks in two cross-over periods, each separated by a 2-week
placebo period, according to a randomized, double-blind, cross-over design. At
the end of each study period, clinical as well as 24-h ambulatory BP and HR were
evaluated. RESULTS: A total of 25 subjects were included in the analysis. At the
end of a 4-week diazepam treatment, clinical as well 24-h BP and HR mean values
were not significantly affected. Analysis of sub-periods showed that during night
time, systolic BP (SBP) values under diazepam were 7.6% higher than under
placebo, with a mean difference of 7.9 mmHg (p < 0.01), diastolic BP (DBP) values
were 5.8% higher, with a mean difference of 3.7 mmHg (p < 0.05 vs placebo) and HR
values were 6.6% higher with a mean difference of 4.2 b/min (p < 0.05). The HR
increase observed with diazepam persisted during the morning hours, whereas
during the afternoon and evening hours SBP, DBP and HR values were similar in the
two treatment groups. CONCLUSIONS: In elderly subjects chronic assumption of
diazepam as hypnotic agent produced an increase in BP, in particular SBP, during
night-time and of HR during night-time and morning hours. These effects, which
probably depend on a diazepam-mediated increase in sympathetic drive and decrease
in vagal tone, might be of clinical relevance due to the role of increased BP and
HR as independent predictors of cardiovascular morbidity and mortality.
PMID- 29959669
TI - High-Throughput Characterization of Primary microRNA Transcripts.
AB - Proper control of microRNA (miRNA) expression is critical for normal development
and physiology, while abnormal miRNA expression is a common feature of many
diseases. Dissecting mechanisms of miRNA regulation, however, is complicated by
the generally poor annotation of miRNA primary transcripts (pri-miRNAs). Although
some miRNAs are processed from well-defined protein coding genes, the majority of
pri-miRNAs are poorly characterized noncoding RNAs, with incomplete annotation of
promoters, splice sites, and polyadenylation signals. Due to the efficiency of
DROSHA processing, the abundance of pri-miRNAs is very low at steady state,
thereby complicating the elucidation of pri-miRNA structures. Here we describe a
strategy to enrich intact pri-miRNAs and improve their coverage in RNA sequencing
(RNA-seq) experiments. In addition, we outline a computational approach for
reconstruction of pri-miRNA structures. This pipeline begins with raw RNA-seq
reads and concludes with publication-ready visualization of pri-miRNA
annotations. Together, these approaches allow the user to define and explore
miRNA gene structures in a cell-type or organism of interest.
PMID- 29959668
TI - Abnormal Effective Connectivity of the Anterior Forebrain Regions in Disorders of
Consciousness.
AB - A number of studies have indicated that disorders of consciousness result from
multifocal injuries as well as from the impaired functional and anatomical
connectivity between various anterior forebrain regions. However, the specific
causal mechanism linking these regions remains unclear. In this study, we used
spectral dynamic causal modeling to assess how the effective connections (ECs)
between various regions differ between individuals. Next, we used connectome
based predictive modeling to evaluate the performance of the ECs in predicting
the clinical scores of DOC patients. We found increased ECs from the striatum to
the globus pallidus as well as from the globus pallidus to the posterior
cingulate cortex, and decreased ECs from the globus pallidus to the thalamus and
from the medial prefrontal cortex to the striatum in DOC patients as compared to
healthy controls. Prediction of the patients' outcome was effective using the
negative ECs as features. In summary, the present study highlights a key role of
the thalamo-basal ganglia-cortical loop in DOCs and supports the anterior
forebrain mesocircuit hypothesis. Furthermore, EC could be potentially used to
assess the consciousness level.
PMID- 29959670
TI - Identifying Pri-miRNA Transcription Start Sites.
AB - MicroRNAs (miRNAs) are small non-coding RNAs that can regulate gene expression
playing vital role in nearly all biological pathways. Even though miRNAs have
been intensely studied for more than two decades, information regarding miRNA
transcription regulation remains limited. The rapid cleavage of primary miRNA
transcripts (pri-miRNAs) by Drosha in the nucleus hinders their identification
with conventional RNA-seq approaches. Identifying the transcription start site
(TSS) of miRNAs will enable genome-wide identification of their expression
regulators, including transcription factors (TFs), other non-coding RNAs (ncRNAs)
and epigenetic modifiers, providing significant breakthroughs in understanding
the mechanisms underlying miRNA expression in development and disease. Here we
present a protocol that utilizes microTSS, a versatile computational framework
for accurate and single-nucleotide resolution miRNA TSS predictions as well as
miRGen, a database of miRNA gene TSSs coupled with genome-wide maps of TF binding
sites.
PMID- 29959671
TI - Metabolic Pulse-Chase RNA Labeling for pri-miRNA Processing Dynamics.
AB - miRNA biogenesis is a multistep process starting with the cleavage of the primary
miRNA transcript in the nucleus by the microprocessor complex. The pri-miRNA
processing kinetics has a high impact on the final regulative role of the mature
miRNAs on the expression of their target transcripts. Thus studying the in vivo
kinetics of the miRNA biogenesis could give more insights into the contribution
of each individual miRNA on regulation of gene expression. Here, we describe step
by step a method to determine the processing kinetics of pri-miRNAs in vivo,
using a pulse-chase approach that can be used in downstream applications such as
qPCR or deep sequencing. We explain in detail the various aspects of this
approach that can be applied to different mammalian cell types. The nature of
this protocol allows the in vivo study of pri-miRNA processing kinetics in cells
treated with different conditions, mutants, and/or cancer cell lines under
physiological conditions.
PMID- 29959672
TI - In Vitro System for Coupling RNAP II Transcription to Primary microRNA Processing
and a Three-Way System for RNAP II Transcription/Splicing/microRNA Processing.
AB - In the genome, primary microRNAs (pri-miRNAs) are encoded either as independent
transcriptional units with their own promoters (intergenic miRNAs) or within the
introns of other genes (intronic miRNAs). Here, we report two methods, one that
we established for coupled RNAP II transcription and pri-miRNA processing and the
other that is a three-way system for RNAP II transcription, pri-miRNA processing,
and pre-mRNA splicing. In these systems, CMV-DNA constructs encoding the
processing substrates are incubated in HeLa cell nuclear extracts in the presence
of 32P-UTP to generate the nascent RNAP II transcripts, which are processed
efficiently by the endogenous RNA processing machineries in nuclear extracts.
PMID- 29959673
TI - Purification of Microprocessor-Associated Factors.
AB - The Microprocessor complex catalyzes the first step of miRNA biogenesis in the
nucleus of mammalian cells. The minimal catalytically active complex is formed by
two essential factors, the dsRNA binding protein DGCR8, and the RNase III
endonuclease Drosha. Importantly, several co-factors can associate to this
complex and modulate the cleavage and binding efficiency of this complex, in a
positive or negative manner. Here, we describe a simple method for purification
of DGCR8 and Drosha coupled to mass spectrometry or western blot which allows
robust identification of unknown associated factors. This approach has recently
revealed the presence of a new DGCR8-dependent, Drosha-independent complex
involved in RNA turnover.
PMID- 29959674
TI - Inhibiting Pri-miRNA Processing with Target Site Blockers.
AB - The pri-miRNA processing is important for the final regulatory role of miRNAs on
the expression of their target transcripts. The processing variability between
pri-miRNAs can determine the final miRNA abundance better than primary
transcription itself. Thus studying the in vivo pri-miRNA biogenesis could give
more insights into the contribution of each individual miRNA on regulation of
gene expression. Interfering processing of a specific pri-miRNA has been
challenging due to the nature of the current RNA interfence methods. Here, we
describe step by step a method to arrest processing of specific pri-miRNAs in
vivo using LNA microRNA Target Site Blockers. We explain in detail the various
aspects of this approach that can easily be applied to different mammalian cell
types. The nature of this protocol allows the in vivo study of pri-miRNA
processing and processing kinetics in cells treated with different conditions,
mutants, and/or cancer cell lines under physiological conditions.
PMID- 29959675
TI - MicroRNA Analysis Using the Quantitative Real-Time PCR Reaction.
AB - The analysis of microRNA expression patterns provides new insights into numerous
cellular processes and their aberrances in diseases. Despite its potential
pitfalls, the quantitative real-time polymerase chain reaction (qPCR) is the most
commonly used tool for microRNA profiling. The method requires extraction and
quality analysis of RNA, which is further reverse transcribed using specific
primers and used as a template in a qPCR reaction. All these elements have been
addressed in this chapter.
PMID- 29959676
TI - MicroRNA Analysis Using Next-Generation Sequencing.
AB - Next-generation sequencing (NGS) enables the analysis of both microRNA expression
and sequence, allowing for elucidation of a comprehensive landscape of miRNAs in
a given tissue and sample type. NGS analysis requires high-quality RNA extraction
and preparation of microRNA libraries. In this chapter, we describe the methods
used for RNA extraction from tissue specimens, serum, cytological slides, and
formalin-fixed paraffin-embedded samples. Although the described library
preparation and sequencing approaches are based on Illumina NextSeq 500
sequencing technology, the presented principles shall be compatible with other
commercially available sequencing platforms.
PMID- 29959677
TI - Identification of microRNA Precursor-Associated Proteins.
AB - MicroRNA (miRNA) biogenesis is regulated intricately at multiple levels. In
addition to transcriptional control of pri-miRNA loci, sequence as well as
structural features of the pri-miRNA-stem loop determine its processing
efficiency by the endonucleases Drosha and Dicer. On the one hand, general
features are necessary to allow a hairpin to be recognized by the processing
machinery; on the other hand, specific sequence motifs of individual miRNA
precursors can be read by RNA binding proteins (RBPs) that regulate processing,
leading to increased or decreased levels of functional miRNAs. In a pulldown
experiment using the pri-miRNA hairpin as immobilized bait, cognate RBPs can be
isolated and analyzed by immunoblotting or mass spectrometry, allowing for the
discovery or analysis of protein regulators of miRNA biogenesis.
PMID- 29959678
TI - Analysis of 3' End Modifications in microRNAs by High-Throughput Sequencing.
AB - MicroRNAs are ~22 nt small, non-coding RNAs that direct posttranscriptional
silencing of gene expression to regulate animal development, physiology, and
disease. An emerging mechanism that controls the biogenesis of microRNAs is the
addition of non-templated nucleotides, predominantly uridine, to the 3' end of
precursor-microRNAs, in a process that is commonly referred to as tailing. Here,
we describe methods that enable the systematic characterization of tailing events
in mature microRNAs and their precursors. We report protocols for untargeted and
targeted cDNA library preparation procedures, as exemplified in the context of
the model organism Drosophila melanogaster and focusing on precursor-microRNAs.
We also refer to a dedicated computational framework for the subsequent analysis
of untemplated nucleotide additions in cDNA libraries. The described methods for
the systematic characterization of posttranscriptional modifications in gene
regulatory small RNAs and their precursors will be instrumental in clarifying
regulatory concepts that control posttranscriptional gene silencing.
PMID- 29959679
TI - Uncovering the Stability of Mature miRNAs by 4-Thio-Uridine Metabolic Labeling.
AB - MicroRNAs (miRNAs) are an evolutionary conserved class of short, single-stranded
noncoding RNAs (<18-22 nt in length) that act in posttranscriptional regulation
of gene expression in higher eukaryotes. The abundance of a miRNA is a key
feature in control of its activity and, therefore, a number of mechanisms finely
regulate miRNA levels, acting at both transcriptional and posttranscriptional
level. Recent evidences, including our research, highlighted the role of miRNA
decay as a mechanism controlling the miRNA pool. We describe in this chapter an
optimized methodology to determine miRNA degradation rates in mammalian cells.
Our approach is based on metabolic pulse labeling with 4-thiouridine (4sU), a
uridine analog that is incorporated in nascent RNA and allows thiol-specific
biotinylation and selective pull-down of labeled RNA. In particular, given the
long average half-life and the complex biogenetic process of miRNAs, we developed
a "pulse-chase" protocol where 4sU is removed from the medium after a long
labeling period (2-3 h pulse), and labeled RNA is purified at different time
points to measure the decay of labeled molecules. By combining the 4sU-based
"pulse-chase" approach with high-throughput small RNA sequencing (sRNAseq), it is
possible to quantify at genome-wide level miRNA degradation rates.
PMID- 29959680
TI - Detection of microRNA-Target Interactions by Chimera PCR (ChimP).
AB - MicroRNAs (miRNAs) regulate gene expression by directing Argonaute proteins to
target RNAs, which usually results in destabilization and translational
inhibition of the target RNA. The prediction of animal miRNA target sites has
remained a challenge due to the ability of miRNAs to bind target RNAs through
imperfect base pairing. Recently, several labs have established methods to
produce biochemical evidence of miRNA-target interactions by generating chimeric
reads where the miRNA is ligated to its target RNA. Despite the insights that can
be gained from chimera producing methods, the current approaches are inefficient,
labor intensive and require computational expertise. Here we describe a method,
called Chimera PCR (ChimP), for the validation or testing of specific miRNA
target interactions. This method allows for focused experiments to analyze miRNA
targeting in a variety of conditions.
PMID- 29959681
TI - High-Quality Overlapping Paired-End Reads for the Detection of A-to-I Editing on
Small RNA.
AB - Paired-end RNA sequencing (RNA-seq) is usually applied to the quantification of
long transcripts such as messenger or long non-coding RNAs, in which case
overlapping pairs are discarded. In contrast, RNA-seq on short RNAs (<= 200 nt)
is typically carried out in single-end mode, as the additional cost associated
with paired-end would only translate into redundant sequence information. Here,
we exploit paired-end sequencing of short RNAs as a strategy to filter out
sequencing errors and apply this method to the identification of adenosine-to
inosine (A-to-I) RNA editing events on human precursor microRNA (pre-miRNA) and
mature miRNA. Combined with RNA immunoprecipitation sequencing (RIP-seq) of A-to
I RNA editing enzymes, this method takes full advantage of deep sequencing
technology to identify RNA editing sites with unprecedented resolution in terms
of editing efficiency.
PMID- 29959682
TI - Targeting miRNA for Therapeutics Using a Micronome Based Method for
Identification of miRNA-mRNA Pairs and Validation of Key Regulator miRNA.
AB - MicroRNAs are 18-22 bp long non-coding sequences and play a critical role in
diverse biological processes, through modulation of gene expression at the post
transcriptional level by binding at the 3'-untranslated region of target mRNA.
Consequent upon the discovery of structural and functional features of miRNA
targeting, several molecular methods have been developed to identify miRNA
targets. However, these methods suffer several drawbacks, including technical
challenges, requirement of high cell volumes, inability to differentiate between
direct and indirect targets, cell/tissue as well as experimental-specificity and
imprecise binding site information. Alternatively in silico approach enables the
exploration of the potential miRNA-mRNA pairs to investigate signature miRNA and
proteins involved in the signaling of various diseases. Here, we describe
micronome-based standard method for identification of miRNA-mRNA pairs as well as
validation of key regulator miRNA.
PMID- 29959683
TI - Method for Detection of miRNAs in Non-Model Organisms with Unreported Database.
AB - Non-model organisms are studied very frequently, as a simple accessible and
convenient system to investigate the role of miRNAs in particular aspect of
biology or disease. However, the unavailability of the annotated genome and hence
miRNA database of these non-model organisms pose a major constraint for using
them more efficiently. Here, we describe a new method to identify miRNAs in non
model organisms without complex sequencing strategies and using miRNAs from close
relative organisms as proxy/reference sequences.
PMID- 29959684
TI - Detection and Verification of Mammalian Mirtrons by Northern Blotting.
AB - microRNAs (miRNAs) have vital roles in regulating gene expression-contributing to
major diseases like cancer and heart disease. Over the last decade, thousands of
miRNAs have been discovered through high throughput sequencing-based annotation.
Different classes have been described, as well as a great dynamic range of
expression levels. While sequencing approaches provide insight into biogenesis
and allow confident identification, there is a need for additional methods for
validation and characterization. Northern blotting was one of the first
techniques used for studying miRNAs, and remains one of the most valuable as it
avoids enzymatic manipulation of miRNA transcripts. Blotting can also provide
insight into biogenesis by revealing RNA processing intermediates. Compared to
sequencing, however, northern blotting is a relatively insensitive technology.
This creates a challenge for detecting low expressed miRNAs, particularly those
produced by inefficient, non-canonical pathways. In this chapter, we describe a
strategy to study such miRNAs by northern blotting that involves ectopic
expression of both miRNAs and miRNA-binding Argonaute (Ago) proteins. Through use
of epitope tags, this strategy also provides a convenient method for verification
of small RNA competency to be loaded into regulatory complexes.
PMID- 29959685
TI - Detecting Agotrons in Ago CLIPseq Data.
AB - Timely and accurate regulation of gene expression is essential to all organisms.
MicroRNAs (miRNAs) are a well-characterized and important class of gene
expression regulators. We recently identified a novel class of gene regulators,
the agotrons. Agotrons derive from short introns and associate with Argonaute
(Ago) proteins much similar to miRNAs. However, agotrons completely bypass the
conventional miRNA biogenesis pathway and thus exist as full-length introns,
which disobey the classical rules on Ago-substrate requirements. As a class,
agotrons are conserved in mammals, and despite the non-canonical biogenesis
pathway, agotrons maintain the ability to deregulate mRNAs with seed-matches in
the 3'UTR. While several pipelines exist for the detection of miRNAs, no
bioinformatics toolkit has yet been developed to specifically identify agotrons.
Here, we describe a simple approach, termed agotron_detector (
https://github.com/ncrnalab/agotron_detector ), to identify and quantify agotrons
in Ago CLIPseq datasets. Hopefully, this allows researchers worldwide to
characterize agotrons in more detail and to reveal the biological relevance of
these fascinating RNA species.
PMID- 29959687
TI - General Data Protection Regulation (GDPR) and paediatric medical practice in
Ireland: a personal reflection.
PMID- 29959686
TI - Stress Granule Formation is One of the Early Antiviral Mechanisms for Host Cells
Against Coxsackievirus B Infection.
AB - Stress granules (SGs) are intracellular granules formed when cellular translation
is blocked and have been reported to be involved in a variety of viral
infections. Our previous studies revealed that SGs are involved in the
coxsackievirus B (CVB) infection process, but the role of SGs in CVB infection
has not been fully explored. In this study, we found that CVB type 3 (CVB3) could
induce SG formation in the early phase of infection. Results showed that levels
of CVB3 RNA and protein were significantly inhibited during the early stage of
CVB3 infection by the elevated formation of SGs, while viral RNA and protein
synthesis were significantly promoted when SG formation was blocked. Our findings
suggest that SG formation is one of the early antiviral mechanisms for host cells
against CVB infection.
PMID- 29959688
TI - Identifying and Managing Hibernating Myocardium: What's New and What Remains
Unknown?
AB - PURPOSE OF REVIEW: Hibernation is an important and reversible cause of myocardial
dysfunction in ischaemic heart failure. RECENT FINDINGS: Hibernation is an
adaptive process that promotes myocyte survival over maintaining contractile
function. It is innate to mammalian physiology, sharing features with
physiological hibernation in other species. Advanced imaging methods have
reasonable accuracy in identifying hibernating myocardium. Novel superior hybrid
methods may provide diagnostic potential. New evidence supports the role of
surgical revascularisation in ischaemic heart failure, but the role of viability
tests in planning such procedures remains unclear. Research to date has
exclusively involved patients with ambulatory heart failure: Investigating the
role of hibernation in ADHF is a key avenue for the future. Whilst our
understanding of hibernation pathophysiology has improved dramatically, the
clinical utility of identifying and targeting hibernation remains unclear.
PMID- 29959690
TI - Connecting with a Slot Machine: Social Exclusion and Anthropomorphization
Increase Gambling.
AB - Two studies tested whether social exclusion can increase gambling behavior. In
Study 1, participants were asked to relive a socially painful instance, a
physically painful instance or a control condition and were then presented with a
real online gambling device (i.e., a slot machine). The results revealed that
participants who relived a socially painful instance played longer on the
gambling device. In Study 2, we induced actual feelings of social disconnection
and manipulated slot machine anthropomorphization. The results revealed a
significant interaction between inclusionary status and anthropomorphism in
predicting gambling. More specifically, excluded participants gambled longer when
presented with an anthropomorphized slot machine. However, the gambling behavior
of excluded and included participants was no different when participants were
reminded that slot machines are inanimate objects. Finally, positive and negative
game experience mediated the influence of both inclusionary status and
anthropomorphism on gambling. Overall, this research identifies another potential
vulnerability produced by experiences of social exclusion, namely, gambling
behavior. Implications for pathological gambling and future research directions
are outlined.
PMID- 29959691
TI - Decision-Making Styles, Negative Affectivity, and Cognitive Distortions in
Adolescent Gambling.
AB - Evidences from the extant literature suggest that problem gamblers show higher
cognitive distortions and reported experiencing higher levels of negative
affective states than recreational gamblers. Furthermore, several studies
reported that the more the gambling severity, the poorer the performance in
behavioral tasks assessing affective decision-making. Although gambling research
on decision-making has mostly focused on the functional or dysfunctional outcomes
of the decisional process, no study examined the role of decision-making styles
in gambling disorder. This study aimed to first investigate the interplay among
negative affectivity, cognitive distortions, and decision-making styles in
adolescent problem gambling. Four hundred and twenty-five adolescents, aged
between 14 and 19 years, completed the South Oaks Gambling Screen Revised for
Adolescents to assess problem gambling, the Depression Anxiety and Stress Scales
21 to measure negative affective states, and the Gambling Related Cognitions
Scale as a measure of cognitive distortions about gambling, and the General
Decision-Making Style tapping habitual patterns which individuals use in decision
making. Data were submitted to correlational analysis, univariate and mixed-model
ANOVAs, and hierarchical regression analysis. Regression analysis indicated that,
along with gender, interpretative bias and inability to stop gambling,
depression, and spontaneous decision-making style significantly predicted
gambling severity. These results extend further previous studies on the role of
misconceptions about gambling, and negative affective states in adolescent
gambling, and, interestingly, first demonstrate that also maladaptive decision
making styles may represent a risk factor for gambling disorder.
PMID- 29959689
TI - Cognitive functioning and quality of life in patients with Hashimoto thyroiditis
on long-term levothyroxine replacement.
AB - OBJECTIVE: Intrinsic imperfections of thyroid hormone replacement therapy may
affect long-term general well-being. In patients with Hashimoto thyroiditis (HT),
cognitive functioning may be affected via altered thyroid hormones action as well
as by the autoimmune process. The aim of this study was to evaluate cognitive
function and quality of life (QoL) in patients on long-term levothyroxine
replacement for HT in relation to thyroid function tests and TPO (thyroid
peroxidase) antibody (TPOAb) status. DESIGN: Retrospective cross-sectional study.
PATIENTS AND MEASUREMENTS: One-hundred-and thirty patients with HT on long-term
levothyroxine replacement and 111 euthyroid control subjects. Both groups were
divided into two age subgroups, 20-49 years (N = 59 vs N = 79) and > 50 years (N
= 71 vs N = 32). Evaluation included biochemical and neuropsychological tests,
evaluating attention, global cognitive status, verbal and working memory,
executive function, depression and anxiety, and quality of life. We used ANOVA
and partial correlations to test for significant associations. RESULTS: FT4 (free
thyroxine), FT3 (free-triiodothyronine) levels and FT3/FT4 ratio were not
different between patients and controls. Mean TSH (thyroid-stimulating hormone)
was normal in all subjects but significantly higher in the patients (20-49
yrs:3.64 +/- 2.74 vs 1.93 +/- 1.10, >50 yrs:3.93 +/- 2.84 vs 1.91 +/- 0.90).
Antibodies (TgAb,TPOAb) were higher in patients. Global cognitive function (MMSE
Mini mental state examination), conceptual tracking (TMT-Trail Making Test:A/B),
verbal divergent thinking (like Phonemic fluency test), and anxiety and
depression scores were significantly worse in patients vs controls. QoL was
impaired in patients. there was a significant negative correlation between
antibodies (TPOAb, TgAb) and quality in life (total SF36 score). CONCLUSION:
Patients on long-term levothyroxine replacement show persistent impairments in
both cognitive functioning and general well-being.
PMID- 29959692
TI - Underlying Mechanism of the Comorbid Presence of Buying Disorder with Gambling
Disorder: A Pathways Analysis.
AB - Buying disorder (BD) and gambling disorder (GD) are behavioral addictions that
are increasingly being researched and treated by mental health professionals.
This study analyzes the underlying mechanisms of the comorbidity between both
conditions in a sample of treatment-seeking patients. The sample included n = 127
patients recruited from a specialized unit in addictive behaviors at a public
university hospital who presented BD symptoms with and without GD. Structural
equation models analyzed the mediational mechanisms that explained the presence
of the comorbid condition BD + GD. Personality variables indirectly influence the
concurrence of GD and BD, and the relationship patterns were modulated by the age
of onset of these two conditions. A direct relationship between being male and an
increase in the risk of GD + BD comorbidity was also found. Sex and the amount of
disorder-related debts also were directly associated with psychopathology. These
results provide evidence on the pathways of concurrent BD + GD, which could
contribute to the development of evidence-based preventive and therapeutic
interventions.
PMID- 29959693
TI - Cell-Free eccDNAs: A New Type of Nucleic Acid Component for Liquid Biopsy?
AB - Extrachromosomal circular DNAs (eccDNAs) are circular DNAs that are originated
from chromosomes, but are independent from chromosomal DNA. The eccDNAs are
commonly found in various tissues and cell types, and in both normal and diseased
conditions. Due to their highly heterogeneous origins and being widely spread in
nearly all eukaryotes, the eccDNAs are believed to reflect the genome's
plasticity and instability. With the assistance of next-generation sequencing,
more eccDNAs have been characterized at the molecular level. Recently, eccDNAs
have been reported as cell-free DNAs in the circulation system. Importantly,
these circulating eccDNAs have shown some evidence with disease associations,
suggesting their potential utility as a new type of biomarker for disease
detection, treatment assessment and progress surveillance. However, many
challenges need to be addressed before implementing the eccDNAs as a new source
of genetic material for liquid biopsy.
PMID- 29959694
TI - Features of diffuse gliomas that are misdiagnosed on initial neuroimaging: a case
control study.
AB - PURPOSE: The neuroimaging diagnosis of diffuse gliomas can be challenging owing
to their variable clinical and radiologic presentation. The purpose of this study
was to identify factors that are associated with imaging errors in the diagnosis
of diffuse gliomas. METHODS: A retrospective case-control analysis was
undertaken. 18 misdiagnosed diffuse gliomas on initial neuroimaging (cases) and
108 accurately diagnosed diffuse gliomas on initial neuroimaging (controls) were
collected. Clinical, pathological, and imaging metrics were tabulated for each
patient. The tabulated metrics were compared between cases and controls to
determine factors associated with misdiagnosis. RESULTS: Cases of misdiagnosed
diffuse glioma (vs controls) were more likely to undergo initial triage as a
stroke workup [OR 14.429 (95% CI 4.345, 47.915), p < 0.0001], were less likely to
enhance [OR 0.283 (95% CI 0.098, 0.812), p = 0.02], were smaller (mean diameter
4.4 vs 6.0 cm, p = 0.0008), produced less midline shift (median midline shift 0.0
vs 2.0 mm, p = 0.003), were less likely to demonstrate necrosis [OR 0.156 (95% CI
0.034-0.713), p = 0.008], and were less likely to have IV contrast administered
on the initial MRI [OR 0.100 (95% CI 0.020, 0.494), p = 0.008]. CONCLUSION:
Several clinical and radiologic metrics are associated with diffuse gliomas that
are missed or misdiagnosed on the initial neuroimaging study. Knowledge of these
associations may aid in avoiding misinterpretation and accurately diagnosing such
cases in clinical practice.
PMID- 29959695
TI - Postoperative seizures in meningioma patients: improving patient selection for
antiepileptic drug therapy.
AB - BACKGROUND: Epilepsy is a major cause of morbidity and mortality in meningioma
patients. The aims of this study were to determine which factors predispose
meningioma patients to developing perioperative seizures and to understand the
impact of antiepileptic drugs. METHODS: Patients treated for a histologically
confirmed intracranial meningioma at the authors' institution between 2010 and
2015 were retrospectively examined. Clinical and imaging data were assessed.
Multivariate analysis was performed using binary logistic regression. The effect
of antiepileptic treatment was assessed using survival analysis. RESULTS: Two
hundred and eighty-three patients met the selection criteria; seizures were
present in 68 preoperatively (24%) and in 48 patients (17%) following surgery. Of
the 68 with preoperative seizures, 19 continued to have them, whereas de-novo
seizures arose postoperatively in 29 seizure-naive patients. Risk factors of
postoperative seizures were convexity location (OR 2.05 [95% CI 1.07-3.98], p =
0.030), fronto-parietal location (OR 4.42 [95% CI 1.49-13.16], p = 0.007) and
preoperative seizures (OR 2.65 [95% CI 1.37-5.24], p = 0.005). The two locations,
in addition to the presence of midline shift on preoperative imaging (OR 4.15
[95% CI 1.54-11.24], p = 0.005), were significantly correlated with postoperative
seizures in seizure-naive patients. Antiepileptic treatment in patients with
those risk factors reduced the possibility of seizures at any time point within
the 1st year postoperatively by approximately 40%, although this did not meet
statistical significance. CONCLUSION: Prophylactic antiepileptic treatment might
be warranted in seizure-naive meningioma patients with >= 1 risk factor. High
quality randomised controlled trials are required to verify those factors and to
define the role of antiepileptics in meningioma practice.
PMID- 29959697
TI - Normal Human Thyrocytes in Culture.
AB - In order to study functions of normal human thyrocytes, we developed a protocol
to obtain these cells in primary culture. Thyrocytes are obtained from normal
tissue obtained at surgery for removal of thyroid neoplasms. Under sterile
conditions, specimens are minced into small pieces, mono-dispersed cells are
generated by digestion with collagenase type IV and the cells plated in tissue
culture grade dishes in Dulbecco's modified Eagle's medium (DMEM) containing 10%
fetal bovine serum (FBS). After 24 h of incubation at 37 degrees C in a
humidified 5% CO2 incubator, the supernatant containing non-adherent cells is
removed and the adherent cells are propagated in DMEM with 10% FBS, 100 IU/mL
penicillin, and 10 MUg/mL streptomycin. Cells proliferate with a doubling time of
72-94 h and retain functional characteristics for 9-12 doublings. We have used
them successfully in studies to elucidate the signaling by thyrotropin (TSH) and
insulin-like growth factor 1.
PMID- 29959696
TI - Prevalence and Comorbidities of Resistant Hypertension: A Collaborative
Population-Based Observational Study.
AB - BACKGROUND: Resistant hypertension, is a clinical condition that may confer high
cardiovascular risk. Aim of the observational study was to evaluate the
prevalence of resistant hypertension, and the association with cardiovascular
risk factors or diseases in the Verona urban area. DESIGN AND METHODS: Eleven
family doctors retrieved anonymised data concerning blood pressure, diagnosis of
hypertension and treatments from a population of 17,502 adult subjects. The
prevalence of resistant hypertension was estimated considering patients who had
been consecutively treated with at least four antihypertensive medications,
regardless of blood pressure values. Further search concerning the clinical
characteristics associated with resistant hypertension was performed in a random
subsample of 55 patients. RESULTS: The prevalence of hypertension was 21.9%, that
of resistant hypertension was 2.1%, approximately 10% of the whole hypertensive
population. High prevalence of diabetes mellitus (53%) and hyperlipidemia (83%)
was found in association with resistant hypertension. As for end organ damage,
high prevalence of carotid artery stenosis (45%), ischemic heart disease (43%)
and left ventricular hypertrophy (40%) was observed in patients with resistant
hypertension. Blood pressure was higher than 140/90 mmHg in 58% of patients in
spite of treatment with four or more different antihypertensive drugs. The
average age, systolic and pulse pressure were significantly higher in the
subgroup of patients with resistant hypertension. CONCLUSIONS: Patients with
resistant hypertension are characterised by a higher systolic and pulse pressure
and a very high attributable cardiovascular risk, due to high prevalence of
cardiovascular risk factors and overt organ damage and cardiovascular disease.
PMID- 29959698
TI - Isolation and Culture of Juvenile Pig Thyroid Follicular Epithelia.
AB - Epithelial tissues are defined by their polarity and their ability to transport
directionally. Thyroid is a tissue comprising functional epithelial units
organized as enclosed follicles, with their luminal spaces defined by thyrocyte
apices. Thus, the native arrangement of thyroid epithelia limits accessibility to
the follicular space, presenting a challenge in studying transepithelial
movements. This limitation can be overcome by studying thyrocytes grown as two
dimensional cultures. Herein we present methods for isolation of thyroid
follicles from juvenile pigs and preparation of high-resistance, polarized
cultures.
PMID- 29959699
TI - Reassembly of Functional Human Stem/Progenitor Cells in 3D Culture.
AB - This chapter focuses on the culture of primary human cells from the salivary
glands, typically parotid but also submandibular, where specialized acinar cells
produce most of the components found in saliva and the intercalated ducts
followed by striated ducts transport saliva to the oral cavity. Compared to many
other epithelial cells, the zymogen-filled salivary acinar cells are very
fragile, hence specialized techniques are needed to isolate and culture them. To
reestablish the function of implantable 3D reassembled glands using tissue
engineering approaches, it is critical to culture these cells in human-based
matrices that permit them to move, reassemble, interconnect, and establish proper
polarity by producing a basement membrane. Our team is working to develop a
biologically based, implantable salivary gland replacement tissue for head and
neck cancer patients suffering from post-radiation xerostomia using a "bottom up"
reassembly paradigm. We use specialized extracellular matrix and growth factor
supplemented hyaluronate hydrogels to promote reassembly of human salivary
stem/progenitor cells (hS/PCs) isolated after surgical resection, a method we
describe in this chapter. Cell-specific biomarkers are used to track the
formation of the three major epithelial cell types comprising the salivary gland:
acinar, ductal, and myoepithelial.
PMID- 29959700
TI - Culture and Differentiation of Lung Bronchiolar Epithelial Cells In Vitro.
AB - Club cells are a major bronchiolar epithelial cell type in the lung. Using
genetic lineage tracing in mice and in vitro culture of purified cells, we have
shown that club cells can differentiate into alveolar type I and II cells. Here
we describe the detailed protocol for culturing and differentiating club cells in
3-dimensional culture.
PMID- 29959701
TI - Differentiation of Gastrointestinal Cell Lines by Culture in Semi-wet Interface.
AB - Epithelial cells grown in vitro provide opportunities to elucidate cellular
mechanisms in response to chemical, viral, or bacterial agents in isolation from
the effects of other bodily functions, such as hormonal and immune responses.
However, cells that do not form a tight epithelium, polarize or secrete mucins
lack some of the important protection mechanisms intrinsic to epithelial cells in
vivo, increasing their susceptibility to external agents, and exposing
basolateral targets for interactions that may not occur in vivo. Here, we present
a method that transforms some epithelial cell lines into mucin secreting
polarized epithelial surfaces with high transepithelial resistance: the cells are
cultured on semi-permeable membranes in differentiation medium for the first 6
days, followed by culture under semi-wet interface with mechanical stimulation
for 22 days. The procedure can be performed using standard laboratory reagents
and equipment. A description on how to fix and paraffin embed these in vitro
mucosal membranes for histology purposes is also included.
PMID- 29959702
TI - Three-Dimensional Cell Culture Model Utilization in Renal Carcinoma Cancer Stem
Cell Research.
AB - Specific 3D conditions of cancer cell lines have been optimized over last years,
with growing significance of serum-free and xeno-free culture variants. The
choice of proper culture media enables cancer stem cells proliferation in primary
and stable cell lines. To obtain renal cell cancer stem-like phenotype, we
employed media dedicated for mesenchymal cells and adult stem cells. Developed
RCC cell line 3D culture system enables effective drug testing, including
tyrosine kinase inhibitor anti-cancer cell toxicity. To induce formation of 3D
spheroids by RCC cell lines, StemXvivo and NutriStem media must be used. Usage of
laminin- or poly-D-lysine coated plates enhances also the formation of spheroids
in 3D-promoting media. Seeding is optimal with Caki-1 or ACHN cell lines as well
as 786-O or HKCSC cells. Our bio-mimic 3D RCC cell culture model promotes cell
viability and stem-related gene expression including E-cadherin, N-cadherin,
HIF1, HIF2, VEGF, Sox2, Pax2, and Nestin. 3D spheroid formation ability and
spheroid volume increase are disturbed upon drug treatment. Untreated 3D
structures reach ~100 MUm in diameter at the end of 14-day long experiment.
Sorter-based cell cycle analysis and Ki-67 staining should be conducted to verify
specific toxicity. We suggest that due to the more complex architecture 3D RCC
culture is more relevant to investigate the in vivo-like tumor drug response.
PMID- 29959703
TI - Amniotic Epithelial Cell Culture.
AB - Ovine amniotic epithelial cells (oAEC) are a subset of placental stem cells with
great regenerative and immunomodulatory properties. Indeed, oAEC are object of
intense study for regenerative medicine thanks to the several advantages in
developing pre-clinical studies on a high value translational animal model, such
as sheep. For this reason, a critical standardization of cultural practices is
fundamental to preserve in vitro oAEC native phenotype, thus improving their in
vivo therapeutic potential and clinical outcomes. Here is described an improved
oAEC cultural protocol able to preserve the native epithelial phenotype also
after the in vitro amplification.
PMID- 29959704
TI - Bovine Granulosa Cell Culture.
AB - Culture of granulosa cells has for long provided a useful tool to understand the
molecular processes underlying ovarian follicle development. Among all species
investigated, cattle have become an excellent model for in vitro studies on
follicular biology, both because of their resemblance with humans in terms of
follicular biology and the importance of reproductive failure as a cause of lost
productivity in the dairy industry. In this chapter, we describe up-to-date
methods for the harvesting of granulosa cells from bovine ovaries collected post
mortem, as well as procedures for both culturing granulosa cells in an
undifferentiated state and inducing their luteinization in vitro, and for the
efficient transfection of granulosa cells with oligonucleotide sequences for the
purpose of investigating the function of specific genes in vitro.
PMID- 29959705
TI - Bioencapsulation of Oocytes and Granulosa Cells.
AB - A protocol for the encapsulation in sodium alginate of granulosa cells in primary
culture and co-culture of oocyte-cumulus complexes is reported. Sodium alginate
forms strong gels when jellified with barium ions, allowing the self-organization
of cells into a 3D structure. This method of encapsulation is simple and cheap,
allowing the culture of cells in a 3-dimensional fashion.
PMID- 29959706
TI - Ovine Granulosa Cells Isolation and Culture to Improve Oocyte Quality.
AB - The functional cooperation between the oocyte and its surrounding granulosa cells
is mandatory to oocyte growth and acquisition of developmental competence in
mammalian species. Availability of in vitro methods for culture granulosa cells
is important in understanding the biology of these cells and the response of
maturing oocyte to in vitro culture and co-culture. Using the ovine as a model
the ensuing chapter describes methods for primary culture of ovine granulosa
cells and their co-culture with theca cells or oocytes that allow to mimic the
molecular interactions between somatic cells and maturing oocyte and improve
oocyte quality.
PMID- 29959707
TI - 3D Model Replicating the Intestinal Function to Evaluate Drug Permeability.
AB - Animal models are essential in drug development but present many concerns in the
practical and ethical sense. To avoid the unnecessary use of animals other models
are used in the beginning of any scientific discovery, the in vitro models. The
relevance of in vitro cell based culture models for studying intestinal drug
absorption and transcytosis during early stages of drug development is
undeniable. Several in vitro co-culture models have been described for this
purpose, however excluding the integration of the complex intestinal architecture
and neglecting different physiological mechanisms involved in the drug transport.
2-D cell cultures are the current standard, but despite their widely use, they no
longer are considered the most trustworthy in vitro models since they do not
mimic many aspects that happen in vivo. The simulation of a complete
microenvironment capable of mimicking the intestinal mucosa requires therefore
further investigation, particularly focused in addressing the abovementioned
unmet needs. 3D models came as bridge between the in vitro and in vivo models.
These models are proven to be influential of the drug effect in cells, being the
most adequate to mimic the live tissue especially in drug development. Supported
by the great amount of studies using simple and reductionist co-culture
monolayers, and pushing forward an innovative model previously reported by our
group, the present study aims to describe a sophisticated and highly reproducible
in vitro 3D co-culture intestinal model. Here, the components are assembled in a
multistage process into Transwell filters by co-culturing human colon carcinoma
Caco-2 and mucus-producing HT29-MTX cells over a layer of collagen embedding
intestinal myofibroblasts (CCD-18Co). The 3D co-culture intestinal model
described herein represents a particularly powerful and versatile tool that
recapitulates the intestinal functioning regarding mucus production, tightness of
the different cell types, and the 3D architecture, bridging the gap between
simple monolayer cultures of epithelial cells and the complex in vivo
physiological conditions. Importantly, it shows tremendous potential in
predicting intestinal absorption of orally administered drugs when delivered
alone, or encapsulated into micro- and nanosystems, the current leading force of
pharmaceutical technology research.
PMID- 29959708
TI - Isolation of Human Gastric Epithelial Cells from Gastric Surgical Tissue and
Gastric Biopsies for Primary Culture.
AB - The epithelium of human gastric mucosa is involved in secretory and digestive
functions, and distinct epithelial populations located in specific compartments
of the gastric pit-gland units mediate these functions. We successfully developed
a method for the isolation and growth of normal human gastric epithelial cells
using biopsies or surgically resected tissues as the source of the cells. Gastric
epithelial cell aggregates were released from the underlying tissues by gentle
enzymatic digestion of collagenase type IV. Primary cultures were generated by
seeding viable multicellular aggregates on plastic without a biological matrix.
Characterized by immunostaining of cell-specific antigens, the cells were
confirmed to be heterogenous gastric epithelial primary cultures containing mucus
cells, neck cells, parietal cells, chief cells, and gastrin-secreting endocrine
cells. This simple and convenient method will prove useful in the isolation of
normal human gastric mucous epithelial cells for in vitro studies of gastric
epithelial biology.
PMID- 29959709
TI - Long-Term Culture of Intestinal Organoids.
AB - The in vitro long-term expansion of primary intestinal epithelial cells has been
hampered by the inability to maintain an immature stem cell population. Recent
technical advances have led to the development of a novel in vitro culture system
that can sustain intestinal stem cells (ISCs) using growth factors that mimic the
intestinal microenvironment in combination with a three-dimensional (3D) culture.
The resulting intestinal organoids display a crypt-villus architecture that
recapitulates the native intestinal epithelium. Here, we describe our method for
the long-term culture of intestinal epithelial organoids via consistent passaging
using a gentle cell dissociation reagent to easily break the organoid into
smaller pieces. The long-term cryopreservation and defining characteristics of
these intestinal organoids also make this work relevant for the advancement of
epithelial organoid-based therapeutic technologies by allowing the production of
large numbers of cells for use in clinical applications.
PMID- 29959710
TI - Bovine Mammary Organoids: A Model to Study Epithelial Mammary Cells.
AB - Bovine mammary organoids are cell aggregates that are produced by an association
of a mechanical and an enzymatic dissociation of mammary gland tissue. They
provide a useful source to isolate mammary epithelial cells, but can also be
frozen as an intermediate dissociation step.Due to the strong cell-cell
interactions among epithelial cells, the production and isolation of organoids is
an efficient way to remove unwanted cell population of non-epithelial origin like
fibroblasts.
PMID- 29959711
TI - Establishment of Human- and Mouse-Derived Gastric Primary Epithelial Cell
Monolayers from Organoids.
AB - Organoid cultures generated from gastrointestinal tissues have been an invaluable
advancement for in vitro studies of physiological function and disease. Here we
present a comprehensive protocol for the establishment and culture of human- and
mouse-derived 3-dimensional gastric organoids transferred to 2-dimensional
gastric epithelial cell monolayers. We introduce two methods that include the
establishment of monolayers from: (1) intact organoids, and (2) single cells
dissociated from intact organoids.
PMID- 29959712
TI - Mouse-Derived Gastric Organoid and Immune Cell Co-culture for the Study of the
Tumor Microenvironment.
AB - The interaction between the receptor, programmed cell death protein 1 (PD-1) and
ligand, programmed cell death 1 (PD-L1) is known to inhibit CD8+ cytotoxic T
lymphocyte proliferation, survival, and effector function. The result of this
interaction leads to evasion of immune surveillance by tumors and subsequently
cancer cell proliferation. Immunotherapy via PD-L1 blockade is used for a variety
of malignancies, yet the prognostic value of immune checkpoint inhibition for the
treatment of gastric cancer remains controversial. Thus, preclinical models that
would predict the efficacy of such therapy in a subgroup of gastric cancer
patients would be an advancement in the personalized treatment of this disease.
Three-dimensional organoid cultures have not only been used to investigate the
mechanisms regulating development and disease, but have also been used for high
throughput drug screening for targeted personalized therapy. Here we present the
methodology for the co-culture of mouse-derived gastric cancer organoids with
autologous immune cells specifically for the study of PD-L1/PD-1 interactions
within the tumor microenvironment in vitro.
PMID- 29959713
TI - Murine and Human Mammary Cancer Cell Lines: Functional Tests.
AB - The biological characterization of mammary cancer cells is a prerequisite that
helps the scientist understand some aspect of tumor biology. Once isolated from
the tumor, cells are subjected to multiple tests that dissect their ability to
growth, migrate, degrade the surrounding stroma, produce 3-dimensional structures
and differentiate. Targeted inhibitors, when added to these tests, are used to
unravel how specific growth factors, receptors, and intracellular translational
pathways promote the ability of mammary tumor cells to achieve their biological
behavior. Herein we describe a set of techniques used to put in focus the
biological capacities in mammary cancer cells. When the characterization of a
biological trait (e.g., proliferation) is assessable by multiple assays, we will
limit the description to only one technique, possibly the easier to manage and
that requires minimal laboratory equipment.
PMID- 29959714
TI - In Vitro Porcine Colon Culture.
AB - Models have been extensively used to investigate disease pathogenesis. Animal
models are costly, require extensive logistics for animal care, and samples are
not always suitable for different analytical techniques or to answer the research
question. In vitro cell culture models are generally focused on recreating a
specific characteristic of an organ, and are limited to a single cell population
that does not display the characteristic tissue architecture of the source organ.
In addition, such models do not account for the many interactions between
pathogens and the diverse cell subsets that are normally present in a given
organ. Conclusions based on conventional 2D cell culture methods are limited,
requiring extrapolation from a reductionist model to understand in vivo events.
In vitro organ culture (IVOC) offers a way to overcome some of these limitations.
Explants conserve important in vivo characteristics, such as different cell types
and complex tissue architecture. This in vitro (ex vivo) organ culture protocol
of the swine large intestine aims at maintaining viable colonic mucosa for up to
5 days. The protocol described herein applies a combination of methods used for
immortalized cell culture and stem cell stimulation to support the physiological
cellular flow inherent of the intestinal mucosa. Required equipment includes a
hyperoxic chamber and culture at the air-liquid interface.
PMID- 29959715
TI - Primary Cultures of Olfactory Neurons from the Avian Olfactory Epithelium.
AB - The culture of the olfactory epithelium has been a useful model for the study of
neurogenesis since olfactory neurons regenerate continuously throughout the adult
lifespan. Structurally and functionally mature olfactory neurons are generated in
vitro from non-neuronal precursors in a process that resembles the in vivo
counterparts. This chapter describes a technique for culture of olfactory neurons
from the avian olfactory epithelium of embryonic chickens; this enables the
controlled laboratory study of a critical sensory system that is unstudied in
this major vertebrate class. The techniques described here are broadly applicable
to other endothermic vertebrate species.
PMID- 29959716
TI - Encompassing Cultural Contexts Within Scientific Research Methodologies in the
Development of Health Promotion Interventions.
AB - American Indians/Alaska Natives/Native Hawaiians (AI/AN/NHs) disproportionately
experience higher rates of various health conditions. Developing culturally
centered interventions targeting health conditions is a strategy to decrease the
burden of health conditions among this population. This study analyzes
characteristics from 21 studies currently funded under the Interventions for
Health Promotion and Disease Prevention in Native American (NA) Populations
program among investigators currently funded under this grant mechanism. Four
broad challenges were revealed as critical to address when scientifically
establishing culturally centered interventions for Native populations. These
challenges were (a) their ability to harness culture-centered knowledge and
perspectives from communities; (b) their utilization of Indigenous-based theories
and knowledge systems with Western-based intervention paradigms and theories; (c)
their use of Western-based methodologies; and (d) their cultural adaptation, if
based on an evidence-based treatment. Findings revealed that qualitative
methodologies and community-based participatory research (CBPR) approaches were
very commonly used to finalize the development of interventions. Various
Indigenous-based theories and knowledge systems and Western-based theories were
used in the methodologies employed. Cultural adaptations were made that often
used formative mixed qualitative and quantitative methods. Illustrative examples
of strategies used and suggestions for future research are provided. Findings
underscored the importance of CBPR methods to improve the efficacy of
interventions for AI/AN/NH communities by integrating Indigenous-based theories
and knowledge systems with Western science approaches to improve health.
PMID- 29959717
TI - Embracing Causal Complexity in Health Disparities: Metabolic Syndemics and
Structural Prevention in Rural Minority Communities.
AB - Chronic discrimination and associated socioeconomic inequalities have shaped the
health and well-being of Black Americans. As a consequence of the intersection of
these factors with rural deprivation, rural Black Americans live and work in
particularly pathogenic environments that generate disproportionate and
interacting chronic comorbidities (syndemics) compared to their White and/or
urban counterparts. Traditional prevention research has been unable to fully
capture the underlying complexity of rural minority health and has generated
mostly low-leverage interventions that have failed to reverse adverse metabolic
outcomes among rural Black Americans. In contrast, novel research approaches-such
as system dynamics modeling-that seek to understand holistic system structure and
determine complex health outcomes over time provide a robust framework to develop
a more accurate understanding of the key factors contributing to type 2 diabetes.
This framework can then be used to establish more efficacious interventions to
address disparities among minorities in rural areas. This paper advocates for a
unified complex systems epistemology and methodology in advancing rural minority
health disparities research. Toward this goal, we (1) provide an overview of
rural Black American metabolic health research, (2) introduce a complex systems
framework in rural minority health disparities research, and (3) demonstrate how
community-based system dynamics modeling and simulation can help us plow new
ground in rural minority health disparities research and action. We anticipate
that this paper can serve as a catalyst for a long-overdue discourse on the
relevance of complex systems approaches in minority health research, with
practical benefits for numerous disproportionately burdened communities.
PMID- 29959718
TI - Multi-level Determinants of Clinic Attendance and Antiretroviral Treatment
Adherence Among Fishermen Living with HIV/AIDS in Communities on Lake Victoria,
Uganda.
AB - This cross-sectional study assessed determinants of HIV clinic appointment
attendance and antiretroviral treatment (ART) adherence among 300 male fisherfolk
on ART in Wakiso District, Uganda. Multi-level factors associated with missed HIV
clinic visits included those at the individual (age, AOR = 0.98, 95% CI 0.97
0.99), interpersonal (being single/separated from partner, AOR: 1.25, 95% CI 1.01
1.54), normative (anticipated HIV stigma, AOR: 1.55, 95% CI 1.05-2.29) and
physical/built environment-level (travel time to the HIV clinic, AOR: 1.11, 95%
CI 1.02-1.20; structural-barriers to ART adherence, AOR: 1.27, 95% CI 1.04-1.56;
accessing care on a landing site vs. an island, AOR: 1.35, 95% CI 1.08-1.67).
Factors associated with ART non-adherence included those at the individual (age,
beta: - 0.01, eta2 = 0.03; monthly income, beta: - 0.01, eta2 = 0.02) and
normative levels (anticipated HIV stigma, beta: 0.10, eta2 = 0.02; enacted HIV
stigma, beta: 0.11, eta2 = 0.02). Differentiated models of HIV care that
integrate stigma reduction and social support, and reduce the number of clinic
visits needed, should be explored in this setting to reduce multi-level barriers
to accessing HIV care and ART adherence.
PMID- 29959719
TI - Sexual Agreements: A Scoping Review of Measurement, Prevalence and Links to
Health Outcomes.
AB - A sexual agreement is a mutual understanding between two partners regarding
sexual and relational behaviors both within and outside of their relationship.
Sexual agreements have been central to research and programming efforts around
HIV prevention, primarily for male couples. A comprehensive scoping review of the
primary literature on sexual agreements, including negotiated safety, was
performed to identify what is known about sexual agreements among couples (n =
66). Results indicate a wide range of prevalence of agreements and measurements
used to characterize sexual agreements. Findings also report associations between
sexual agreements and health and relational outcomes. Several knowledge gaps were
identified; specifically, the need to expand sexual agreements research beyond
MSM populations and the need to better understand agreement breaks, break
disclosure, and how variation in agreement categorization may impact reported
prevalence. This review demonstrates the importance of broadening the evidence
base of sexual agreements research and programmatic focus.
PMID- 29959720
TI - Early Breastfeeding Cessation Among HIV-Infected and HIV-Uninfected Women in
Western Cape Province, South Africa.
AB - As part of the Mother-Infant Health Study, we describe infant feeding practices
among HIV-infected and HIV-uninfected mothers over a 12-month period when the
Western Cape Province prevention of mother-to-child transmission (PMTCT) program
was transitioning from a policy of exclusive formula feeding to one of exclusive
breastfeeding. Two hundred pairs of mother and HIV-uninfected infant were
included in the analysis, among whom 81 women were HIV uninfected and
breastfeeding. Of the 119 HIV-infected mothers, 50 (42%) were breastfeeding and
69 (58%) were formula feeding. HIV-infected mothers predominantly breastfed for
8.14 (7.71-15.86) weeks; HIV-uninfected mothers predominantly breastfed for 8.29
(8.0-16.0) weeks; and HIV-infected mothers predominantly formula fed for 50.29
(36.43-51.43) weeks. A woman's HIV status had no influence on the time to
stopping predominant breastfeeding (P = 0.20). Our findings suggest suboptimal
duration of breastfeeding among both HIV-infected and HIV-uninfected mothers.
Providing support for all mothers postdelivery, regardless of their HIV status,
may improve breastfeeding practices.
PMID- 29959721
TI - The Use of Efavirenz During Pregnancy is Associated with Suicidal Ideation in
Postpartum Women in Rural South Africa.
AB - Efavirenz is used for the management of HIV infection during pregnancy in South
Africa (SA), but it is contraindicated in patients with history of depression due
to possible suicidal ideation. This study compared suicidal ideation 12-months
postpartum among women receiving and not receiving efavirenz in rural SA, where
high rates of depression have been identified. Antenatal psychological intimate
partner violence (IPV; AOR = 1.04), depression (AOR = 1.06) and detection of
efavirenz in dried blood spot at 32 weeks predicted suicidal ideation 12-months
postnatally (AOR = 2.29), controlling for antenatal stigma and physical IPV.
Findings support using alternative agents for the management of HIV during
pregnancy.
PMID- 29959722
TI - HIV Prevention in Rural Appalachian Jails: Implications for Re-entry Risk
Reduction Among Women Who Use Drugs.
AB - Rural women are at risk for health consequences (such as HIV) associated with
substance misuse, but targeted interventions are limited for this population.
Jails provide an underutilized opportunity for outreach to high-risk women in
rural Appalachian communities. Rural women were randomized to either the NIDA
Standard education intervention (n = 201) or the NIDA Standard plus motivational
interviewing (MI-HIV; n = 199) while in jail. Outcomes focused on HIV risk
behaviors 3 months post-release from jail. Decreases in HIV risk behaviors were
observed at follow-up across conditions. Although participants in the MI-HIV
group showed reductions in outcomes compared to the NIDA Standard group (OR =
0.82-0.93), these estimates did not reach significance (p values > .57). HIV
education interventions can be associated with risk-reduction behaviors. These
findings support the need for increased access to prevention education in
criminal justice venues, particularly in rural communities.
PMID- 29959724
TI - Extra-Alveolar Bone Screws for Conservative Correction of Severe Malocclusion
Without Extractions or Orthognathic Surgery.
AB - PURPOSE OF REVIEW: Evaluate management of challenging malocclusions
conservatively (no extractions or orthognathic surgery). RECENT FINDINGS: Most
malocclusions have a predominately environmental etiology. Optimal esthetics and
function are restored by aligning the dentition over the apical base of bone at
the appropriate vertical dimension of occlusion (VDO). Extra-alveolar (E-A)
anchorage is achieved at three intraoral sites: mandibular buccal shelf (MBS),
infrazygomatic crest (IZC), and anterior ramus. MBS and IZC bone screws
effectively anchor the conservative correction of severe dental and skeletal
malocclusions. All bone screw sites are effective for anchoring lever arms to
recover impacted teeth. Rather than extracting teeth, E-A anchorage corrects
crowding by retracting the posterior segments to increase arch length. Skeletal
malocclusion is corrected by aligning teeth over the apical base of bone and
restoring the VDO by retracting and posteriorly rotating the dental arches as
segments. Challenging dental and skeletal malocclusions can be treated routinely
via determinate mechanics anchored with E-A bone screws.
PMID- 29959723
TI - Origin of Reparative Stem Cells in Fracture Healing.
AB - PURPOSE OF REVIEW: The identity and functional roles of stem cell population(s)
that contribute to fracture repair remains unclear. This review provides a brief
history of mesenchymal stem cell (MSCs) and provides an updated view of the many
stem/progenitor cell populations contributing to fracture repair. RECENT
FINDINGS: Functional studies show MSCs are not the multipotential stem cell
population that form cartilage and bone during fracture repair. Rather, multiple
studies have confirmed the periosteum is the primary source of stem/progenitor
cells for fracture repair. Newer work is also identifying other stem/progenitor
cells that may also contribute to healing. Although the heterogenous periosteal
cells migrate to the fracture site and contribute directly to callus formation,
other cell populations are involved. Pericytes and bone marrow stromal cells are
now thought of as key secretory centers that mostly coordinate the repair
process. Other populations of stem/progenitor cells from the muscle and
transdifferentiated chondroctyes may also contribute to repair, and their
functional role is an area of active research.
PMID- 29959725
TI - Use of Esophageal pH Monitoring to Minimize Proton-Pump Inhibitor Utilization in
Patients with Gastroesophageal Reflux Symptoms.
AB - BACKGROUND: Due to concerns about long-term PPI use in patients with acid reflux,
we aimed at minimizing PPI use, either by avoiding initiating therapy,
downscaling to other therapies, or introducing endoscopic or surgical options.
AIMS: To examine the role of esophageal ambulatory pHmetry in minimizing PPI use
in patients with heartburn and acid regurgitation. METHODS: Retrospective cohort
analysis of patients with reflux symptoms, who underwent endoscopy, manometry,
and ambulatory pHmetry to define the need for PPI. Patients were classified as:
(1) never users; (2) partial responders to PPI; (3) users with complete response
to PPI. Patients were then managed as: (1) PPI non-users; (2) PPI-initiated, and
(3) PPI-continued. RESULTS: Of 286 patients with heartburn and regurgitation, 103
(36%) were found to have normal and 183 (64%) abnormal esophageal acid exposure
(AET). In the normal AET group, 44/103 had not been treated and were not
initiated on PPI. Of the 59 who had previously received PPI, 52 stopped and 7
continued PPI. Hence, PPI were avoided in 96/103 patients (93%). In the abnormal
AET group, 61/183 had not been treated and 38 were initiated on PPI and 23 on
other therapies. In the 122 patients previously treated with PPI, 24 were not
treated with PPI, but with H2RAs, prokinetics, endoscopic, or surgical therapy.
Hence, PPI therapy was avoided in 47/183 patients (26%). CONCLUSIONS: In patients
with GER symptoms, esophageal pHmetry may avert PPI use in 50%. In the era of
caution regarding PPIs, early testing may provide assurance and justification.
PMID- 29959726
TI - Physicians' Perspectives on Cost, Safety, and Perceived Efficacy Determine
Aminosalicylate Use in Crohn's Disease.
AB - BACKGROUND: Aminosalicylates are the most commonly prescribed therapy in Crohn's
disease (CD), despite uncertainty in the evidence to support their efficacy.
AIMS: To examine physicians' perspectives on aminosalicylate use for CD and
explore the discordance between clinical practice and the evidence base. METHODS:
A qualitative interview study was performed amongst physicians with at least 4
years of independent experience in managing CD patients. Semi-structured
telephone interviews were conducted using an exploratory interview guide.
Interview transcripts were thematically analyzed to elucidate concepts pertaining
to treatment strategies for CD, motivations for prescribing aminosalicylates,
perceived benefits and harms of aminosalicylate use, and the relationship between
the evidence and real-world prescribing practices. RESULTS: A representative
sample of thirty physicians from four different countries and multiple practice
environments (university/teaching hospitals, public practice, private/community
practice, and subspecialty gastroenterology clinics) participated. Nearly all
physicians (93.3%, 28/30) reported prescribing aminosalicylates for CD.
Aminosalicylates were endorsed as first-line therapy for mild CD by nearly half
of participants (13/30, 43.3%). A favorable safety profile, possible efficacy in
mild colonic CD, and patient reluctance to step-up to other therapies were
primary motivators for aminosalicylate use. Almost half of respondents (46.7%)
expressed that the evidence informing aminosalicylate efficacy in CD differed
substantially from their own clinical experience. CONCLUSIONS: Physicians'
beliefs about efficacy in subgroups of CD patients, safety, and patient
preferences primarily motivate aminosalicylate prescription in CD. There is a
lack of confidence in published clinical trials, and a desire for more robust
evidence to inform 5-ASA use in CD.
PMID- 29959727
TI - Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis
Through the TNFR1-NF-kappaB/MAPKs Pathway.
AB - BACKGROUND: Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and
its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is
a potential molecule for UC predicted by a computational approach. AIM: The
present study aimed to validate the underlying mechanism of UPF1 in UC. METHODS:
UPF1 expression was detected by qRT-PCR, western blotting, and
immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To
simulate the intestinal inflammation microenvironment, NCM460 human colonic
epithelial cells were exposed to a mixture of inflammatory mediators. The
potential mechanism involving TNFR1-NF-kappaB/MAPKs pathway activation was
addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1
expressing plasmid pENTER-transfected cells. RESULTS: UPF1 was downregulated in
colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA
levels of the associated cytokines enhanced in the UPF1 dysregulation group
within stimulatory factors, most relevant cytokines were significantly decreased
in UPF1 overexpression group. Mechanistically, the increased expression of tumor
necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with
siUPF1, with the activation of IKK/NF-kappaB and MAPKs pathways, including JNK/AP
1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required
the interaction of UPF1 with the promoter. CONCLUSION: UPF1, which negatively
regulated the transcription of TNFR1, is a novel factor regulating intestinal
inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF
kappaB/MAPKs pathway, and promoting inflammatory responses in colon might act as
a causal role in UC.
PMID- 29959729
TI - A Genome-Wide Association Study of alpha-Synuclein Levels in Cerebrospinal Fluid.
AB - alpha-Synuclein is a 140-amino acid protein produced predominantly by neurons in
the brain which plays a role in the regulation of neurotransmitter release,
synaptic function, and plasticity, thus making it the focus in understanding the
etiology of a group of neurodegenerative diseases. We conducted genome-wide
association studies (GWAS) of alpha-synuclein levels in cerebrospinal fluid (CSF)
with 209 non-Hispanic white participants from the Alzheimer's Disease
Neuroimaging Initiative (ADNI-1) cohort using a linear regression model to
identify novel variants associated with alpha-synuclein concentration. The minor
allele (T) of rs7072338 in the long intergenic non-protein coding RNA 1515
(LINC01515) and the minor allele (T) of rs17794023 in clusterin-associated
protein 1 (CLUAP1) were associated with higher CSF alpha-synuclein levels at
genome-wide significance (P = 4.167 * 10-9 and 9.56 * 10-9, respectively). In
addition, single nucleotide polymorphisms (SNPs) near amyloid beta precursor
protein (APP) (rs1394839) (P = 2.31 * 10-7), Rap guanine nucleotide exchange
factor 1 (RAPGEF1) (rs10901091) (P = 8.07 * 10-7), and two intergenic loci on
chromosome 2 and 14 (rs11687064 P = 2.50 * 10-7and rs7147386 P = 4.05 * 10-7)
were identified as suggestive loci associated with CSF alpha-synuclein levels. We
have identified significantly associated SNPs for CSF alpha-synuclein. These
associations have important implications for a better understanding of alpha
synuclein regulation and allow researchers to further explore the relationships
between these SNPs and alpha-synuclein-related neurodegenerative disorders.
PMID- 29959730
TI - Screening of microalgae for treating Garcinia cambogia wash water with potential
lipid production.
AB - The microalgae-based water treatment is gaining importance in recent years as it
serves multiple purposes of which includes water treatment and biofuel
production. Garcinia cambogia, a Malabar tamarind is a tropical fruit and the
active ingredient hydroxycitric acid is popularly used as a weight-loss
supplement. After extraction of the hydroxycitric acid, the wash water of G.
cambogia is considered as an effluent. The potential microalgal species that can
grow and treat G. cambogia wash water were isolated and identified as Dicloster
acuatus BVR1 and Kalenjenia gelanitosa BVR2. Both the microalgal species adapted
to G. cambogia wash water and entered exponential phase after sixth day with
maximum specific growth rate of 0.310 day-1 for D. acuatus and 0.296 day-1 for K.
gelanitosa during tenth day. The biomass productivity of D. acuatus was 0.03 g L
1 day-1 which is 58% higher than K. gelanitosa with 0.019 g L-1 day-1. The
microalgal strains besides water treatment were subsequently subjected for lipid
extraction and lipid productivity determination. The lipid productivity of D.
acuatus was 2.68 mg L-1 day-1 which is lesser compared to 3.38 mg L-1 day-1 for
K. gelatinosa. Both the microalgal isolates were promising for G. cambogia wash
water treatment and lipid production. Hence, an environment friendly approach of
water treatment with simultaneous lipid production for biofuel conversion is
conducted.
PMID- 29959728
TI - Regionally Impaired Redox Homeostasis in the Brain of Rats Subjected to Global
Perinatal Asphyxia: Sustained Effect up to 14 Postnatal Days.
AB - The present report evaluates the effect of global perinatal asphyxia on several
parameters of oxidative stress and cell viability in rat brain tissue sampled at
an extended neonatal period up to 14 days, a period characterised by intensive
neuritogenesis, synaptogenesis, synaptic consolidation, pruning and delayed cell
death. Perinatal asphyxia was induced by immersing foetus-containing uterine
horns removed by a caesarean section from on term rat dams into a water bath at
37 degrees C for 21 min. Asphyxia-exposed and sibling caesarean-delivered
foetuses were manually resucitated and nurtured by surrogate dams for 1 to 14
postnatal (P) days. Brain samples (mesencephalon, telencephalon and hippocampus)
were assayed for glutathione (reduced and oxidated levels; spectrophotometry),
tissue reducing capacity (potassium ferricyanide reducing assay, FRAP), catalase
(the key enzyme protecting against oxidative stress and reactive oxygen species,
Western blots and ELISA) and cleaved caspase-3 (the key executioner of apoptosis,
Western blots) levels. It was found that global PA produced a regionally specific
and sustained increase in GSSG/GSH ratio, a regionally specific decrease in
tissue reducing capacity and a regionally and time specific decrease of catalase
activity and increase of cleaved caspase-3 levels. The present study provides
evidence for regionally impaired redox homeostasis in the brain of rats subjected
to global PA, an effect observed up to P14, mainly affecting mesencephalon and
hippocampus, suggesting a sustained oxidative stress after the posthypoxia
period. The oxidative stress observed postnatally can in part be associated to a
respiratory apneic-like deficit, since there was a statistically significant
decrease in respiration frequency in AS compared to CS neonates, also up to P14,
together with the signs of a decreased peripheral blood perfusion (pink-blue skin
colour in AS, compared to the pink colour observed in all CS neonates). It is
proposed that PA implies a long-term metabolic insult, triggered by the length of
hypoxia, the resuscitation/reoxigenation manoevres, but also by the developmental
stage of the affected brain regions, and the integrity of cardiovascular and
respiratory physiological functions, which are fundamental for warrantying a
proper development.
PMID- 29959731
TI - Simultaneous removal of NO and SO2 from flue gas using vaporized H2O2 catalyzed
by nanoscale zero-valent iron.
AB - To remove NO and SO2 from flue gas simultaneously, a heterogeneous catalytic
oxidation system was developed with the nanoscale zero-valent iron (nZVI),
vaporized H2O2, and sodium humate (HA-Na) acting as the catalyst, oxidant, and
absorbent, respectively. The experimental results indicated that the
desulfurization was mainly influenced by the absorption, and the denitrification
was significantly affected by the catalytic oxidation parameters. Under the
optimal conditions, the simultaneous removal efficiencies of SO2 and NO were 100
and 88.4%, respectively. The presence of .OH during the removal process was
proved by the scavenger tests, and the production of .OH with and without nZVI
was indirectly evaluated by the electron paramagnetic resonance (EPR) and
methylene blue experiments. Moreover, the fresh and aged nZVI were characterized
by a series of techniques and the results suggested that the redox pair Fe2+/Fe3+
released by nZVI could react with H2O2 to provide the sustainable .OH, which was
important for the oxidation from NO and SO2 to NO3- and SO42-. The removal
mechanism was proposed preliminarily based on the correlative experiments,
characterizations, and references.
PMID- 29959732
TI - Organophosphorus poisoning in animals and enzymatic antidotes.
AB - Organophosphorus compounds (OPs) are neurotoxic molecules developed as pesticides
and chemical warfare nerve agents (CWNAs). Most of them are covalent inhibitors
of acetylcholinesterase (AChE), a key enzyme in nervous systems, and are
therefore responsible for numerous poisonings around the world. Many animal
models have been studied over the years in order to decipher the toxicity of OPs
and to provide insights for therapeutic and decontamination purposes.
Environmental impact on wild animal species has been analyzed to understand the
consequences of OP uses in agriculture. In complement, various laboratory models,
from invertebrates to aquatic organisms, rodents and primates, have been chosen
to study chronic and acute toxicity as well as neurobehavioral impact, immune
response, developmental disruption, and other pathological signs. Several
decontamination approaches were developed to counteract the poisoning effects of
OPs. Among these, enzyme-based strategies are particularly attractive as they
allow efficient external decontamination without toxicity or environmental impact
and may be of interest for treatment. Approaches using bioscavengers for
prophylaxis, treatment, and external decontamination are emphasized and their
potential is discussed in the light of toxicological observations from various
animal models. The relevance of animal models, regarding their cholinergic system
and the abundance of naturally protecting enzymes, is also discussed for better
extrapolation of results to human.
PMID- 29959733
TI - Adsorptive removal of endocrine-disrupting compounds and a pharmaceutical using
activated charcoal from aqueous solution: kinetics, equilibrium, and mechanism
studies.
AB - Bisphenol A (BPA), diethyl phthalate (DEP), and carbamazepine (CBZ) have been
widely used in chemical and pharmaceutical fields, and their residues are
detected in various environments. Therefore, to find a suitable method for
removing the compounds from an aqueous solution, an adsorption method by granular
activated charcoal (AC) was studied. To investigate the adsorption properties of
AC, its kinetics, equilibrium, pH effects, and regeneration of AC were examined.
Moreover, its surface properties (i.e., surface area, pore volume, functional
groups, and surface charge) were characterized by N2 adsorption and desorption
isotherm, Fourier transform infrared (FTIR), and zeta potential analyses.
Experimental results show that AC has high removal efficiencies for the target
compounds at the low initial concentration as well as high estimated adsorption
capacities (qm) for DEP, BPA, and CBZ, whose values were 293.4 +/- 18.8, 254.9 +/
16.2, and 153.3 +/- 1.61 mg/g, respectively. In comparison with other adsorbents
based on previously reported results, AC was shown to have generally higher
removability for the three compounds than others. Moreover, it was observed that
AC's ability to adsorb DEP and BPA was dependent on pH because of hydrolysis and
ionization, respectively. Meanwhile, there is no pH effect for CBZ adsorption by
AC. After 3 cycles of adsorption/desorption, AC still maintained 92, 100, and 82%
of initial adsorption capacities for DEP, BPA, and CBZ, respectively. Therefore,
the AC is an effective adsorbent for the removal of endocrine-disrupting
chemicals and pharmaceuticals from aqueous solution.
PMID- 29959734
TI - Equilibrium adsorption study of the adsorptive removal of Cd2+ and Cr6+ using
activated carbon.
AB - The performance of activated carbon (AC) with respect to characterization,
adsorption kinetics, thermodynamics, and isotherms was addressed in this study.
The effects of initial concentration, pH, contact time, ion strength, and
temperature on removal efficiency were also studied. The adsorption isotherms of
Cd2+ and Cr6+ on activated carbon can fit the Langmuir model well, and
correlation coefficients were above 0.99, all higher than the Freundlich and
Temkin models. The maximum adsorption quantities of Cd2+ and Cr6+ were 19.380 and
19.305 mg g-1 at 25 degrees C, respectively. The adsorption capacities of Cd2+
and Cr6+ are clearly pH dependent. The kinetics of the removal of Cd2+ and Cr6+
was in agreement with a pseudo-second-order model, and the adsorption efficiency
of Cd2+ is higher than that of Cr6+. The thermodynamic results showed that
increased temperature is favorable to adsorption. The speciation on activated
carbon was mainly residual Cd2+ and Cr6+, and the potential ecological risk of
Cd2+ is higher than that of Cr6+. The adsorptions of Cd2+ and Cr6+ on activated
carbon were dominated by chelation and ion exchange, respectively.
PMID- 29959735
TI - Analysis of the adsorption and retention models for Cd, Cr, Cu, Ni, Pb, and Zn
through neural networks: selection of variables and competitive model.
AB - In this study, the neural networks are used to predict and explain the behavior
of different edaphological variables in the adsorption and retention of heavy
metals, both isolated and competing. A comparison with the results obtained using
multiple regression, stepwise analysis, and regression trees is performed. In the
neural network technique, CEC amorphous and crystallized oxides and kaolinite in
the clay fraction are the most selected variables for making the optimal models,
while mica and, to a lesser extent, plagioclase, are the next variables selected.
Additionally, a competitive model has been considered, using simultaneously
different metals. In the competitive model, the model predicts a more intense
competence between Pb and Ni for the adsorption process and between Cr and Ni for
the retention process.
PMID- 29959736
TI - Wetlands for wastewater treatment and subsequent recycling of treated effluent: a
review.
AB - Due to water scarcity challenges around the world, it is essential to think about
non-conventional water resources to address the increased demand in clean
freshwater. Environmental and public health problems may result from insufficient
provision of sanitation and wastewater disposal facilities. Because of this,
wastewater treatment and recycling methods will be vital to provide sufficient
freshwater in the coming decades, since water resources are limited and more than
70% of water are consumed for irrigation purposes. Therefore, the application of
treated wastewater for agricultural irrigation has much potential, especially
when incorporating the reuse of nutrients like nitrogen and phosphorous, which
are essential for plant production. Among the current treatment technologies
applied in urban wastewater reuse for irrigation, wetlands were concluded to be
the one of the most suitable ones in terms of pollutant removal and have
advantages due to both low maintenance costs and required energy. Wetland
behavior and efficiency concerning wastewater treatment is mainly linked to
macrophyte composition, substrate, hydrology, surface loading rate, influent
feeding mode, microorganism availability, and temperature. Constructed wetlands
are very effective in removing organics and suspended solids, whereas the removal
of nitrogen is relatively low, but could be improved by using a combination of
various types of constructed wetlands meeting the irrigation reuse standards. The
removal of phosphorus is usually low, unless special media with high sorption
capacity are used. Pathogen removal from wetland effluent to meet irrigation
reuse standards is a challenge unless supplementary lagoons or hybrid wetland
systems are used.
PMID- 29959738
TI - Removal of aromatic and hydrophobic fractions of natural organic matter (NOM)
using surfactant modified magnetic nanoadsorbents (MNPs).
AB - The present study investigated the potential of surfactant modified magnetic
nanoadsorbents (MNPs) for the removal of aromatic and hydrophobic fractions of
natural organic matter (NOM), leading to the formation of trihalomethanes (THMs)
in chlorinated drinking water. Co-precipitation method was used for the synthesis
of MNPs. However, MNPs have a tendency to form an agglomeration. Therefore,
polyethylene glycol (PEG) was used as a surface modifier to reduce the
agglomeration. The PEG-coated MNPs were characterized by field emission scanning
electron microscopy (FESEM), transmission electron microscopy (TEM), energy
dispersive X-ray analysis (EDX), BET surface area, X-ray diffraction (XRD),
Fourier transform spectrometer (FTIR), and zeta (zeta) potential. FESEM
observation indicates that PEG-coated MNPs were spherical in shape and 25 nm in
size. Zeta potential values (- 58.35 to - 74.9 mV) indicated excellent stability
of PEG-MNPs. FTIR spectra indicated the presence of a -CH2 group, responsible for
the chemical interaction between aromatic and humic content. Batch experiments
were conducted by studying the effect of pH, contact time, and adsorbent dosage
on NOM removal. Excellent removal of DOC (94.49%) and UV254 (89.32%) was observed
at the optimum dose of adsorbent (0.75 g/L) and at pH 7.0. Adsorption kinetics
followed pseudo-second-order reaction (R2, 0.973) and occurs by multilayer
chemisorption which is due to the chemical interaction between aromatic and humic
compounds of NOM with MNPs. Thus, MNPs showed great potential as a novel
adsorbent for the removal of aromatic and hydrophobic compounds of NOM and can
significantly be used to curtail the problem of THMs in drinking water supplies.
PMID- 29959737
TI - Stop eating plastic, molecular signaling of bisphenol A in breast cancer.
AB - Breast cancer is the second most common fatal cancer in women. Developing a
breast cancer is a multi-factorial and hormonal-dependent process, which may be
triggered by many risk factors. An endocrine disrupting substance known as
bisphenol A (BPA), that is used greatly in the manufacture of plastic products,
was suggested as a possible risk factor for developing breast cancer. BPA has a
strong binding affinity to non-classical membrane estrogen receptors like
estrogen-related and G protein-coupled (GPER) receptors. Based on animal and in
vitro studies, results showed a link between BPA exposure and increased incidence
of breast cancer. BPA has the ability to alter multiple molecular pathways in
cells namely, G protein-coupled receptor (GPER) pathway, estrogen-related
receptor gamma (ERRgamma) pathway, HOXB9 (homeobox-containing gene) pathway, bone
morphogenetic protein 2 (BMP2) and (BMP4), immunoregulatory cytokine disturbance
in the mammary gland, EGFR-STAT3 pathway, FOXA1 in ER-breast cancer cells,
enhancer of zeste homolog 2 (EZH2), and epigenetic changes. Thus, the
aforementioned alterations cause undesired gene stimulation or repression that
increase risk of developing breast cancer. So, restricting exposure to BPA should
be considered to aid in lowering the risk of developing breast cancer.
PMID- 29959739
TI - Effect of controlled-release fertilizer on N2O emissions and tea yield from a tea
field in subtropical central China.
AB - Tea (Camellia sinensis L.), a perennial leaf-harvested crop, favors warm/humid
climate and acidic/well-drained soils, and demands high nitrogen (N) fertilizer
inputs which lead to significant emissions of N2O. Potential mitigation options
should be adopted to improve N use efficiency (NUE) and reduce environmental
pollution in tea field system. A 3-year field experiment was carried out in a tea
field in southern China from January 2014 to December 2016 to investigate the
effect of controlled-release fertilizer (CRF) application on N2O emissions in tea
field system. Three practices, namely conventional treatment (CON, 105 kg N
oilcake ha-1 year-1 + 345 kg N-urea ha-1 year-1), treatment with a half amount of
the N fertilizer (CRF50%, 105 kg N-oilcake ha-1 year-1 + 120 kg N CRF ha-1 year
1) and full amount of N fertilizer (CRF100%, 105 kg N-oilcake ha-1 year-1 + 345
kg N CRF ha-1 year-1) were used. Compared with the CON, our results showed that
CRF50% reduced the N2O emissions by 26.2% (p > 0.05) and increased the tea yield
by 31.3% (p > 0.05), while CRF100% significantly increased the N2O emissions by
96.7% (p < 0.05) and decreased the tea yield by 6.77% (p > 0.05). Overall, yield
scaled N2O emissions of tea were reduced by 44.5% (p > 0.05) under CRF50% and
significantly increased by 100% (p < 0.05) under CRF100%, compared with CON.
Based on the gross margin analysis, CRF50% obtained the highest net economic
profit. Our findings suggest that reducing N input of CRF (CRF50%) is necessary
and feasible for adoption in the current tea plantation system.
PMID- 29959740
TI - A new concept for risk analysis relating to the degradation of water reservoirs.
AB - This paper presents a proposal for a procedure by which to analyse the risk of
reservoirs being degraded. The body of water assessed for its susceptibility to
degradation in line with the proposed procedure is Myczkowce Reservoir, SE
Poland. This reservoir has a maximum capacity of ten million m3 and helps provide
hydropower, by serving as a surge tank located above the main Solina Reservoir.
On the basis of an assessment of its morphometric and hydrological parameters,
Myczkowce Reservoir was assigned to the low-resilience category where risk of
degradation was concerned. The primary factors responsible for that are limited
capacity in relation to shoreline length, a lack of thermal stratification, and a
high value for the Schindler index. These and other environmental parameters
provided for Myczkowce's assignment to the category of susceptible to the impact
of matter supplied by its catchment, with this reflecting the instantaneous
nature of the basin, high values for the Ohle coefficient, average catchment
slope, and the lack of a septic system. The designated risk level supported
Myczkowce's assignment to a category characterised by an "unacceptable" risk of
degradation. The proposed method taking two parameters (resilience and
susceptibility) into account represents the first universal method for assessing
reservoirs without reference to risks such as drought, flooding, or lack of water
supply for human consumption. The risk depends only on the reservoir and
catchment parameters.
PMID- 29959741
TI - Evaluating the effect of biochar addition on the anaerobic digestion of swine
manure: application of Py-GC/MS.
AB - The anaerobic digestion process of swine manure was studied when char was used as
supplement for improving performance. The use of pyrolysis-gas
chromatography/mass spectrometry (Py-GC/MS) was proposed for assessing the
organic matter degradation. The assessment on biogas production was carried out
using samples of swine manure (SM) supplemented with char in one case and pre
treated by microwave irradiation in the other. This experimental set-up allows
for the comparison of the biological degradation observed under these two
different configurations and therefore aids in understanding the effect of char
particles on the process. Results showed similar performance for both systems,
with an average improvement of 39% being obtained in methane production when
compared to the single digestion of SM. The analysis of digestate samples by
Fourier transform infrared (FTIR) spectroscopy and Py-GC/MS showed improved
degradation of proteins, with the Py-GC/MS technique also capable of identifying
an increase in microbial-derived material when char was added, therefore
highlighting the relevant role of carbon conductive particles on biological
systems. Py-GC/MS along with the use of FTIR spectroscopy has proven to be useful
tools when evaluating anaerobic digestion.
PMID- 29959742
TI - Solubilization of insoluble zinc compounds by zinc solubilizing bacteria (ZSB)
and optimization of their growth conditions.
AB - In this research, the optimum growth conditions for two zinc solubilizing
bacteria (ZSB) have been studied for their potential application as bioinoculants
to overcome Zn unavailability in soils. For this purpose, a laboratory-scale
experiment was carried out to evaluate the zinc solubilizing ability of 80 plant
growth promoting bacteria (PGPB) strains isolated from the rhizosphere of barley
and tomato plants. To select effective ZSB, isolates were evaluated on Tris
mineral medium supplemented separately with zinc oxide, zinc carbonate, and zinc
phosphate at a concentration of 0.1%. Two strains (Agrobacterium tumefaciens and
Rhizobium sp.) were selected, based on a clear halo zone around their colonies in
the solid medium supplemented with zinc oxide after 10 days of incubation at 29
degrees C. Results of solubilization at different pH values showed that these
strains had solubilization activity in the range of pH 8-10 while no
solubilization was observed at pH 6 and 7. The maximum Zn solubilization values
were noted at pH 9: 51.4 mg L-1 (Agrobacterium tumefaciens) and 72.1 mg L-1
(Rhizobium sp). According to findings, bacterial growth was affected by different
NaCl concentrations under in vitro condition. The salt concentration required for
50% inhibition of absorbance was 2.11 and 2.27% NaCl for Agrobacterium
tumefaciens and Rhizobium sp., respectively. The maximum bacterial growth was
observed at about 0.8% NaCl concentration.
PMID- 29959743
TI - Removal of bisphenol A by Fe-impregnated activated carbons.
AB - A commercial wood-based activated carbon and the oxidized counterpart were
impregnated with iron. The two Fe-impregnated carbons were prepared and
characterized for their iron content, textural characteristics, surface
chemistry, and their performance for bisphenol A adsorption. Batch adsorption
experiments were conducted to study the effect of pH, ionic strength, kinetics,
and thermodynamic equilibrium. Equilibrium adsorption data were described by both
Langmuir and Freundlich isotherms. The iron impregnated activated carbon and the
oxidized impregnated activated carbon presented maximum adsorption capacities of
785.65 and 469.78 mg/g, respectively, while adsorption followed second-order rate
kinetics for both impregnated carbons. According to the thermodynamic parameters
(DeltaEtaomicron, DeltaSo, DeltaGo), the adsorption is a spontaneous, exothermic,
and physical process. Fenton-driven experiments conducted at different molar
ratios of [H2O2]/[BPA] showed efficient degradation of BPA in spent Fe
impregnated carbons up to 82-95%, with traces of hydroxylated products.
PMID- 29959744
TI - Application of Metabolomics in the Study of Natural Products.
AB - LC-MS-based metabolomics could have a major impact in the study of natural
products, especially in its metabolism, toxicity and activity. This review
highlights recent applications of metabolomics approach in the study of
metabolites and toxicity of natural products, and the understanding of their
effects on various diseases. Metabolomics has been employed to study the in vitro
and in vivo metabolism of natural compounds, such as osthole,
dehydrodiisoeugenol, and myrislignan. The pharmacological effects of natural
compounds and extracts were determined using metabolomics technology combined
with diseases models in animal, including osthole and nutmeg extracts. It has
been demonstrated that metabolomics is a powerful technology for the
investigation of xenobiotics-induced toxicity. The metabolism of triptolide and
its hepatotoxicity were discussed. LC-MS-based metabolomics has a great potential
in the druggability of natural products. The application of metabolomics should
be broadened in the field of natural products in the future.
PMID- 29959745
TI - Obstetric outcomes and acceptance of alternative therapies to blood transfusion
by Jehovah's Witnesses in Japan: a single-center study.
AB - We sought to investigate obstetric outcomes and acceptance rates for blood
products or types of autotransfusion by Jehovah's Witnesses (JWs) at a single
institution in Japan. We retrospectively reviewed cases of 84 pregnant JW
patients and 95 deliveries from April 2001 to August 2017. We examined the
acceptance rates of blood transfusions, blood products, and autotransfusion types
in patients who experienced postpartum hemorrhage (PPH), and investigated
estimated hemorrhage volume at delivery and PPH treatments. Of the 84 JW
patients, none accepted blood transfusion; however, 75 patients (89.3%) accepted
blood products, 57 (67.9%) accepted autotransfusion using intraoperative cell
salvage, and four (4.8%) refused all alternatives to blood transfusion.
Furthermore, PPH > 1000 mL occurred in 18 of the 95 (18.9%) deliveries. Of these
18 patients, four (22.2%) required blood products and three (16.7%) required
supracervical hysterectomy to control PPH. No maternal deaths occurred.
Approximately 95% of the patients observed accepted all or some alternatives to
blood transfusion. To treat JW patients in a safer manner, understanding their
individual acceptance of alternatives to blood transfusion is important for the
strategic use of such alternatives.
PMID- 29959746
TI - Circulating tumor DNA dynamically predicts response and/or relapse in patients
with hematological malignancies.
AB - A growing body of evidence suggests that tumor-derived fragmentary DNA, known as
circulating tumor DNA (ctDNA), has the potential to serve as a non-invasive
biomarker for disease monitoring. However, in the setting of hematological
malignancy, few published studies support the utility of ctDNA. We
retrospectively investigated ctDNA levels of 17 patients with various
hematological malignancies who had achieved remission after first-line therapy.
We identified somatic driver mutations by next-generation sequencing, and
designed droplet digital PCR assays for each mutation to measure ctDNA. Variant
allele frequencies of ctDNA changed in association with clinical response in all
patients. Eight patients clinically relapsed after a median of 297 days post
first-line therapy (termed, "relapsed group"); the remaining nine patients
remained disease-free for a median of 332 days (termed, "remission group"). Among
patients in the relapsed group, ctDNA levels increased more than twofold at
paired serial time points. In marked contrast, ctDNA levels of all patients in
the remission group remained undetectable or stable during clinical remission.
Notably, ctDNA-based molecular relapse demonstrated a median 30-day lead time
over clinical relapse. In summary, ctDNA monitoring may help identify hematologic
cancer patients at risk for relapse in advance of established clinical
parameters.
PMID- 29959748
TI - Characterization of ABC transporter genes, sll1180, sll1181, and slr1270,
involved in acid stress tolerance of Synechocystis sp. PCC 6803.
AB - Over 50 ATP-binding cassette (ABC) transporter-related genes are detected in the
Synechocystis sp. PCC 6803 genome by genome sequence analysis. Deletion mutants
of other substrate-unknown ABC transporter genes were screened for their acid
stress sensitivities in a low-pH medium to identify ABC transporters involved in
acid resistance. We found that a mutant of sll1180 encoding proteins with
homology to HlyB in Escherichia coli (E.coli) is more sensitive to acid stress
than wild-type (WT) cells and analyzed the abundance of expression of the genes
in WT cells under acid stress condition by quantitative real-time reverse
transcriptase-polymerase chain reaction. sll1180 expression increased in the WT
cells after acid stress treatment. Immunofluorescence revealed that Sll1180
localized in the plasma membrane. These results suggest that Sll1180 has an
important role in the growth of Synechocystis sp. PCC 6803 under acid stress
conditions. HlyB, HlyD, and TolC complex transport HlyA in E.coli; therefore, we
searched for genes corresponding to these in Synechocystis sp. PCC 6803. A BlastP
search suggested that HlyA, HlyD, and TolC proteins had homology to Sll1951,
Sll1181, and Slr1270. Therefore, we constructed deletion mutant of these genes.
sll1181 and slr1270 mutant cells revealed acid stress sensitivity. The bacterial
two-hybrid analysis showed that Sll1180 interacted with Sll1181 and Sll1951. Dot
blot analysis of Sll1951-His revealed that the sll1180 and sll1181 mutant cells
did not transport Sll1951-His from the cytoplasm to the extracellular matrix.
These results suggest that Sll1180 and Sll1181 transport Sll1951 and that Sll1951
outside of the cells-might be a key factor in acid stress tolerance.
PMID- 29959747
TI - Extracorporeal photopheresis with TC-V in Japanese patients with steroid
resistant chronic graft-versus-host disease.
AB - There are few established therapies for chronic graft-versus-host disease (cGVHD)
refractory to first-line treatment with steroids. We evaluated the efficacy and
safety of extracorporeal photopheresis (ECP) with a third-generation TC-V device
in Japanese patients with cGVHD. Fifteen patients with steroid-resistant or
intolerant cGVHD after allogeneic hematopoietic stem cell transplantation
participated in this multicenter open-label study. Extracorporeal photopheresis
was conducted on days 1-3, week 1; days 1-2, weeks 2-12; and days 1-2, weeks 16,
20, and 24. The composite primary endpoint consisted of evaluation of response
and changes in steroid dose 24 weeks after ECP initiation. Secondary endpoints
included response over time, concomitant drug dose, quality of life, and safety.
Twelve patients completed scheduled ECP therapy; eight (66.7%) showed a response
at week 24. In all 15 patients, the mean (+/- standard deviation) steroid dose
decreased 0.115 +/- 0.230 mg/kg/day from screening to week 24. Five serious,
potentially treatment-related adverse events (heart failure, thrombosis in the
device, pneumonia, edema, and wheezing) occurred; none were fatal. This study
confirmed that ECP using the TC-V device was effective, with an acceptable
toxicity profile. Further studies in larger cohorts are clearly warranted to
determine its optimal use in Japanese patients with cGVHD.
PMID- 29959750
TI - Policies on Chinese Medicine in China May Have Enlightenments to Complementary
and Alternative Medicine in the World.
AB - From the event of TU You-you winning the Nobel Prize, this paper briefly reviewed
the history of formation and development of policies on Chinese medicine (CM) in
China. On the basis of analyzing the causes of policies on CM, it is believed
that policies on CM in China may have 4 kinds of enlightenments to the
development of complementary and alternative medicine (CAM) in the world. Forming
the political advantages of policy-making by main leaders of the country
attaching importance to CAM; implementing a diversified health care system policy
for the goal of maximizing people's health interests; ensuring development of CAM
by the coerciveness of law and the timeliness of policy adjustment; and promoting
the protection and mining, sorting out and improving of CAM based on open and
comprehensive policies.
PMID- 29959749
TI - Important photosynthetic contribution of silique wall to seed yield-related
traits in Arabidopsis thaliana.
AB - In plants, green non-foliar organs are able to perform photosynthesis just as
leaves do, and the seed-enclosing pod acts as an essential photosynthetic organ
in legume and Brassica species. To date, the contribution of pod photosynthesis
to seed yield and related components still remains largely unexplored, and in
Arabidopsis thaliana, the photosynthetic activity of the silique (pod) is
unknown. In this study, an Arabidopsis glk1/glk2 mutant defective in both leaf
and silique photosynthesis was used to create tissue-specific functional
complementation lines. These lines were used to analyze the contribution of
silique wall photosynthesis to seed yield and related traits, and to permit the
comparison of this contribution with that of leaf photosynthesis. Our results
showed that, together with leaves, the photosynthetic assimilation of the silique
wall greatly contributed to total seed yield per plant. As for individual
components of yield traits, leaf photosynthesis alone contributed to the seed
number per silique and silique length, while silique wall photosynthesis alone
contributed to thousand-seed weight. In addition, enhancing the photosynthetic
capacity of the silique wall by overexpressing the photosynthesis-related RCA
gene in this tissue resulted in significantly increased seed weight and oil
content in the wild-type (WT) background. These results reveal that silique wall
photosynthesis plays an important role in seed-related traits, and that enhancing
silique photosynthesis in WT plants can further improve seed yield-related traits
and oil production. This finding may have significant implications for improving
the seed yield and oil production of oilseed crops and other species with pod
like organs.
PMID- 29959751
TI - Blood-Letting Therapy for Hypertension: A Systematic Review and Meta-Analysis of
Randomized Controlled Trials.
AB - OBJECTIVE: To evaluate the efficacy and safety of blood-letting therapy (BLT) in
treatment of hypertension. METHODS: A comprehensive electronic and manual
bibliographic searches were performed in Cochrane Central Register of Controlled
Trials, Excerpt Medica Database (EMBASE), PubMed, China National Knowledge
Infrastructure, Chinese Scientific Journal Database, Chinese Biomedical
Literature Database, and Wanfang Database to identify randomized controlled
trials (RCTs) in which hypertensive patients were treated with BLT or BLT plus
antihypertensive drugs (BPAD) against placebo, no treatment or antihypertensive
drugs. The Cochrane Risk Assessment Tool was used to assess the methodological
quality of trials. The Review Manager 5.3 software was used for meta-analysis.
RESULTS: A total of 7 RCTs with 637 hypertensive patients from 1989 to 2017 were
identified. Compared with antihypertensive drugs, blood pressure was
significantly reduced by BLT (RR=1.21, 95% CI: 1.01 to 1.44, P=0.03;
heterogeneity: P=0.06, I2=60%) and BPAD (RR=1.25, 95% CI, 1.02 to 1.53, P=0.03;
heterogeneity: P= 0.01, I2=71%). Moreover, a significant improvement in Chinese
medicine syndrome by BLT (RR=1.32; 95% CI: 1.14 to 1.53, P=0.0002; heterogeneity:
P=0.53, I2=0%) and BPAD (RR=1.47; 95% CI: 1.06 to 2.04, P=0.02; heterogeneity:
P=0.13, I2=56%) was identified. The reported adverse effects were well tolerated.
CONCLUSIONS: Although some positive findings were identified, no definite
conclusions regarding the efficacy and safety of BLT as complementary and
alternative approach for treatment of hypertension could be drew due to the
generally poor methodological design, significant heterogeneity, and insufficient
clinical data. Further rigorously designed trials are warranted to confirm the
results.
PMID- 29959752
TI - "Doctor, I have a Sulfa Allergy": Clarifying the Myths of Cross-Reactivity.
AB - Our purpose is to present an evidence-based approach, directed primarily towards
eye-care specialists, clarifying whether certain drugs should or should not be
used in patients with sulfonamide allergy. We conducted a literature search using
PubMed to identify the risk of ophthalmic-specific drugs in patients with a self
reported sulfonamide allergy. MeSH key words included "sulfonamide" and
"hypersensitivity". Articles specifically geared towards ophthalmic diseases were
sought. The evidence illustrates that individuals with sulfonamide allergy are
intrinsically predisposed to higher rates of allergic reaction that is not
specific towards sulfonamide non-antimicrobials or sulfur-based medications. We
provide a simplified algorithm using the 2017 Clinical Guide to Ophthalmic Drugs
to help busy eye care clinicians determine whether a certain common ophthalmic
medication is safe or unsafe to prescribe in a patient with a "sulfa allergy".
PMID- 29959753
TI - Initial Single-Site Surgical Experience with SMILE: A Comparison of Results to
FDA SMILE, and the Earliest and Latest Generation of LASIK.
AB - INTRODUCTION: The primary objective was to show our initial surgical single-site
experience with small incision lenticule extraction (SMILE) after the official
enrollment in March 2017 following Food and Drug Administration (FDA) approval
for simple myopia in late 2016 in the United States and, subsequently, compare
our results to the earliest and most advanced generation of excimer platforms for
laser-assisted in situ keratomileusis (LASIK) surgery. METHODS: This was a
retrospective single-site study of 68 eyes from 35 patients who had SMILE
surgery. The patients' preoperative and postoperative uncorrected distance visual
acuity (UDVA), corrected distance visual acuity (CDVA), manifest sphere, manifest
cylinder, intraoperative complications, and preoperative and postoperative visual
symptoms were collected. We compared our findings to the results from the FDA
SMILE study, and to the three earliest (1999-2000) and three of the most updated
(2013-2016) platforms for LASIK. RESULTS: The cumulative UDVA was 20/20 and 20/40
or better in 74% and 100% of patients, respectively. The intended target
refraction was within +/- 0.5 and +/- 1.00 D in 80% and 93% of cases,
respectively. The prevalence of dry eyes decreased by nearly half from 1-week to
the 6-month postoperative interval. Patients noted improvement in glare (17%),
halos (17%), fluctuation (25%), and depth perception (8%) at the 6-month interval
compared to preoperative levels. CONCLUSIONS: This study's findings are
consistent with current SMILE reports. Notably, the results are superior to the
earliest generation of LASIK, however inferior to the latest excimer platforms.
SMILE does meet the efficacy and safety criteria met by FDA; however, there is a
definite need for further improvement to reach the superior refractive outcomes
produced by the latest generation of LASIK platforms.
PMID- 29959754
TI - A Prospective Evaluation of Drug Discrimination in Pharmacology.
AB - As investigators, we use many methodologies to answer both practical and
theoretical questions in our field. Occasionally, we must stop and collect the
latest findings or trends and then look forward to where our ideas, findings, and
hypotheses may take us. Similar to volumes that were published in previous years
on drug discrimination (Glennon and Young, Drug discrimination applications to
medicinal chemistry and drug studies. Wiley, Hoboken, 2011; Ho et al., Drug
discrimination and state dependent learning. Academic Press, New York, 1978),
this collection in Current Topics in Behavioral Neurosciences serves as a current
analysis of the continued value of the drug discrimination procedure to the
fields of pharmacology, neuroscience, and psychology and as a stepping stone to
where drug discrimination methodology can be applied next, in both a practical
and theoretical sense. This final chapter represents one investigator's
perspective on the utility and possibilities for a methodology that she fell in
love with over 30 years ago.
PMID- 29959755
TI - Dynamic models of choice.
AB - Parameter estimation in evidence-accumulation models of choice response times is
demanding of both the data and the user. We outline how to fit evidence
accumulation models using the flexible, open-source, R-based Dynamic Models of
Choice (DMC) software. DMC provides a hands-on introduction to the Bayesian
implementation of two popular evidence-accumulation models: the diffusion
decision model (DDM) and the linear ballistic accumulator (LBA). It enables
individual and hierarchical estimation, as well as assessment of the quality of a
model's parameter estimates and descriptive accuracy. First, we introduce the
basic concepts of Bayesian parameter estimation, guiding the reader through a
simple DDM analysis. We then illustrate the challenges of fitting evidence
accumulation models using a set of LBA analyses. We emphasize best practices in
modeling and discuss the importance of parameter- and model-recovery simulations,
exploring the strengths and weaknesses of models in different experimental
designs and parameter regions. We also demonstrate how DMC can be used to model
complex cognitive processes, using as an example a race model of the stop-signal
paradigm, which is used to measure inhibitory ability. We illustrate the
flexibility of DMC by extending this model to account for mixtures of cognitive
processes resulting from attention failures. We then guide the reader through the
practical details of a Bayesian hierarchical analysis, from specifying priors to
obtaining posterior distributions that encapsulate what has been learned from the
data. Finally, we illustrate how the Bayesian approach leads to a quantitatively
cumulative science, showing how to use posterior distributions to specify priors
that can be used to inform the analysis of future experiments.
PMID- 29959756
TI - An analysis of an item-response strategy based on knowledge retrieval.
AB - In this paper, we hypothesize a type of item-response strategy based on knowledge
retrieval. Knowledge retrieval-based item-solving strategy may emerge when: (1)
one's regular ability is not utilized, (2) fast response time is not necessarily
applied, and (3) the accuracy rate may be higher than the expected level due to
chance. We propose to utilize item-response time with a finite-mixture IRT
modeling approach to illustrate a potentially knowledge retrieval-based item
solving strategy. The described strategy is illustrated through the utilization
of a low-stakes assessment data administered under no time constraint. A
simulation study is provided to evaluate the accuracy of the empirical results.
PMID- 29959757
TI - Recent Developments in the Diagnosis and Management of Photosensitive Disorders.
AB - Photodermatoses occur in males and females of all races and ages. Onset can be
variable in timing and influenced by genetic and environmental factors.
Photodermatoses are broadly classified as immunologically mediated, chemical- and
drug-induced, photoaggravated, and genetic (defective DNA repair or chromosomal
instability) diseases. Advances in the field have led to improved recognition and
treatment of many photodermatoses. The purpose of this focused review is to
provide an update on the diagnosis and management of a variety of
photodermatoses, both common and less common, with review of recent updates in
the literature pertaining to their diagnosis and management.
PMID- 29959758
TI - Antidepressants and Hepatotoxicity: A Cohort Study among 5 Million Individuals
Registered in the French National Health Insurance Database.
AB - BACKGROUND: Hepatotoxicity may be a concern when prescribing antidepressants.
Nevertheless, this risk remains poorly understood for serotonin and noradrenaline
reuptake inhibitors (SNRIs: venlafaxine, milnacipran, duloxetine) and 'other
antidepressants' (mianserin, mirtazapine, tianeptine and agomelatine),
particularly in comparison with selective serotonin reuptake inhibitors (SSRIs:
fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram), which
are by far the most commonly prescribed antidepressants. OBJECTIVE: We quantified
the risk of serious liver injury associated with new use of SNRIs and 'other
antidepressants' compared with SSRIs in real-life practice. METHODS: Based on the
French national health insurance database, this cohort study included 4,966,825
individuals aged 25 years and older with a first reimbursement of SSRIs, SNRIs or
'other antidepressants' between January 2010 and June 2015. We compared the risk
of serious liver injury within the 6 months following antidepressant initiation
according to antidepressant class, with SSRIs as the reference, using an inverse
probability-of-treatment-weighted Cox proportional hazard model adjusted for
demographic characteristics and risk factors of liver injury. RESULTS: We
identified 382 serious liver injuries overall (none for milnacipran initiators).
Age and gender standardized incidence rates per 100,000 person-years were 19.2
for SSRIs, 22.2 for venlafaxine, 12.6 for duloxetine, 21.5 for mianserin, 32.8
for mirtazapine, 31.6 for tianeptine and 24.6 for agomelatine initiators.
Initiation of antidepressants of interest versus SSRIs was not associated with an
increased risk of serious liver injury [adjusted hazard ratios (95% confidence
interval): venlafaxine 1.17 (0.83-1.64), duloxetine 0.54 (0.28-1.02), mianserin
0.90 (0.58-1.41), mirtazapine 1.17 (0.67-2.02), tianeptine 1.35 (0.82-2.23) and
agomelatine 1.07 (0.51-2.23)]. This finding was confirmed by the results of an
additional study using a case-time-control design. CONCLUSION: These results do
not provide evidence of an increased risk of serious liver injury following
initiation of SNRIs or 'other antidepressants' compared with SSRIs in real-life
practice. This could reflect an inherent lack of difference in risk between the
drug classes, or the fact that individuals with higher susceptibility to drug
induced liver injury are not prescribed drugs considered to be more hepatotoxic.
PMID- 29959759
TI - Racial, Socioeconomic, and Geographic Disparities in the Receipt, Timing to
Initiation, and Duration of Adjuvant Androgen Deprivation Therapy in Men with
Prostate Cancer.
AB - OBJECTIVE: This retrospective cohort study aims to examine the receipt, timing to
initiation, and duration of androgen deprivation therapy (ADT) in men with
prostate cancer by race/ethnicity, socioeconomic status, and geographic location.
METHODS: The study population are patients from Surveillance, Epidemiology, and
End Results (SEER)-Medicare linked database, who were 66 years or older and newly
diagnosed with stage III and IV prostate cancer in 1992-2009 and underwent
radiation therapy, where ADT was proven to be highly beneficial and its use was
considered as most appropriate (n = 12,170). We use logistic regression to
examine the receipt of ADT and linear regression to study factors associated with
time to ADT initiation while controlling for baseline characteristics. RESULTS:
Overall, 77% of eligible patients received at least one form of ADT in
combination with radiation therapy, of which 12% underwent orchiectomy and the
rest received ADT, and 77.2% of non-Hispanic white and 80.7% of Hispanic patients
received ADT compared to 73.8% of non-Hispanic black. After adjustment for
demographic and tumor characteristics, black men and men of other races are less
likely to receive ADT compared to white counterparts (OR = 0.64 and 0.74,
respectively). The median time from cancer diagnosis to ADT initiation is 2
months. Once initiated, men received a median of seven drug injections. After
controlling for covariates, race/ethnicity and geographic location (SEER areas)
are associated with early initiation of therapy. White, Hispanic men and men
living in the South initiate ADT earlier. CONCLUSION: Significant racial
disparities exist in the receipt and use of this highly beneficial therapy, and
there are geographic variations in the utilization of this therapy.
PMID- 29959760
TI - Correction to: Goal-Striving Stress is Associated with Chronic Kidney Disease
Among Participants in the Jackson Heart Study.
AB - Please note the following correction in the Methods section of this article: The
definition for goal-striving stress in the Jackson Heart Study included
achievement defined as "where one was in life 10 years ago," using a 10-point
scale.
PMID- 29959761
TI - Abortion in Cases of Zika Virus Congenital Infection.
AB - The emergency in international public health caused by the Zika virus gave rise
to the discussion about abortion in cases of congenital Zika virus syndrome
(CZS). Therefore, we propose to carry out a bibliographic review on abortion in
these cases. Five databases were searched using the following terms: abortion,
miscarriage, and zika, with the interposition of the Boolean operator "AND." In
the selected literature, we found references to the lack of information
concerning the risks and severity of CZS, to the great psychological distress
suffered by pregnant women, and to the risk of unsafe abortions as a
justification for abortion in cases of CZS. However, it is necessary to have
available tests that could diagnose, in the first trimester of pregnancy, that
the fetus has been affected by the virus, and that it may have important
limitations, in order to subsidize the qualified discussion about abortion in
these cases.
PMID- 29959762
TI - ["The Big Five" - Cataract Surgery Under Multiple Ocular Comorbidity: Customised
Approach to Prevent Complications].
AB - The co-occurence of 5 diseases (cataract, Fuchs dystrophy, pseudoexfoliation
syndrome, age-related macular degeneration and dry eye syndrome) can lead to
massive impairment of visual acuity. Our case series show that cataract surgery
can lead to an enormous profit in visual rehabilitation and therefore in daily
routine.
PMID- 29959763
TI - Childhood Craniopharyngioma: A 22-Year Challenging Follow-Up in a Single Center.
AB - Craniopharyngioma is a sellar/suprasellar benign tumor whose aggressiveness may
imply in endocrine disturbances (hypothalamic obesity and hormone deficiencies).
Fifty-seven patients were evaluated according to clinical characteristics,
hypothalamic involvement, type of treatment, anthropometric variables, adiposity
indexes (body mass index Z score category at diagnosis and post-treatment, total
body fat, visceral adipose tissue, and metabolic syndrome components) and
analyzed through multiple regression and logistic models. Patients were
stratified according to growth hormone deficiency and recombinant human growth
hormone use. Mean ages at diagnosis and at study evaluation were 9.6 and 16.6
years old, respectively. A set of 43/57 (75.4%) patients presented with important
hypothalamic involvement, 24/57 (42.1%) received surgical treatment and cranial
radiotherapy, and 8/57 (14%) interferon-alpha exclusively. Fifty-five patients
(96.5%) were considered growth hormone deficient, and 26/57 (45.6%) grew despite
no recombinant human growth hormone replacement therapy. At diagnosis, 12/57
(21%) patients were obese, and 33/57 (57.9%) at study evaluation, and after 3.2
years (median) post first therapy. There was no influence of height Z score on
body mass index Z score. Body mass index Z score at diagnosis positively
influenced body mass index Z score, total body fat, waist circumference and the
presence of the metabolic syndrome post-treatment. Replacement of recombinant
human growth hormone decreased total body fat and visceral adipose tissue.
Craniopharyngioma patients worsened body mass index Z score category 3.2 years
(median) after first treatment. Body mass index Z score increased due to real
weight gain, without height decrease. Replacement of recombinant human growth
hormone had beneficial effect on adiposity.
PMID- 29959764
TI - Prospective Series of Nine Long Noncoding RNAs Associated with Survival of
Patients with Glioblastoma.
AB - OBJECTIVE: To analyze the long noncoding RNA (lncRNA) expression profile of
glioblastoma multiforme (GBM) and identify prognosis-related lncRNAs, as well as
their related protein-coding genes and functions. METHOD: The lncRNA expression
profiles were obtained by microarray in six samples each of GBM and normal brain
tissue. The lncRNAs expressed were significantly different between the two groups
and used to detect their associations with patient survival time by downloading
the related data from The Cancer Genome Atlas (TCGA). The total RNA-sequencing
data of 152 patients diagnosed GBM level 3 with complete clinic information was
downloaded. The survival time-dependent lncRNAs were identified by multivariate
Cox regression analysis. For the survival time-dependent lncRNAs, we used the
Pearson correlation coefficient and z test to search their associated protein
coding genes downloaded from TCGA. Functions of these genes were annotated by the
Database for Annotation, Visualization, and Integrated Discovery (DAVID) for gene
ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS:
More than 1,000 antisense lncRNAs and enhancer lncRNAs were selected for analysis
in this study. Data from 152 cases with RNA-seq of GBM level 3 with complete
information on GBM were downloaded from the TCGA database. Univariate Cox
regression analysis revealed 19 lncRNAs with survival time dependency. These nine
lncRNAs were used to construct our survival model via multivariate Cox regression
analysis: TP73-AS1, AC078883.3, RP11-944L7.4, HAR1B, RP4-635E18.7, HOTAIR, SAPCD1
AS1, AC104653.1, and RP5-1172N10.2. The nine lncRNAs associated with them were
inputted into the DAVID database for gene ontology and KEGG function enrichment
analysis. The result showed these genes were enriched with ion binding,
transport, cell-cell signaling, plasma membrane parts, and more, and they were
mainly related to neuroactive ligand-receptor interaction pathway, calcium
signaling pathway, and the mitogen-activated protein kinase signaling pathway.
CONCLUSION: The nine lncRNAs were a set of biomarkers for the prognosis of
patients with GBM, enabling a more accurate prediction of survival and revealing
more biological functions.
PMID- 29959765
TI - Stabilization treatment of remitted psychotic depression: the STOP-PD study.
AB - OBJECTIVE: We conducted a 12-week double-blind study of stabilization
pharmacotherapy in patients with remitted psychotic depression (PD). METHODS:
Seventy-one persons aged 18 years or older who had achieved remission of PD when
randomized to either olanzapine plus sertraline or olanzapine plus placebo were
continued on the double-blind treatment associated with remission. Symptoms of
depression and psychosis, and weight, were measured once every 4 weeks.
Cholesterol, triglycerides, and glucose were measured at stabilization phase
baseline and Week 12/termination. RESULTS: The effect of treatment did not
significantly change with time for depression, weight, or metabolic measures in
the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7)
experienced a relapse of major depression, psychosis, or both. Treatment groups
did not differ in the frequency of relapse. In the entire study group, the
adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83,
2.48) and the adjusted estimate for change in total cholesterol was a decrease of
14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the
remaining metabolic measures did not significantly change. CONCLUSION:
Continuation of acute treatment was associated with stability of remission.
PMID- 29959766
TI - Children's Selective Trust in Promises.
AB - There has been extensive research into the development of selective trust in
testimony, but little is known about the development of selective trust in
promises. The present research investigates children's (N = 264) selective trust
in others' promises to help. In Study 1, 6-year-olds selectively trusted speakers
who had previously kept a promise. In Study 2, 5-year-olds displayed selective
trust for speakers who had previously kept a prosocial promise (promise to help).
In Study 3, 5-year-olds trusted a speaker, who kept a prosocial promise, over a
helper. These data suggest that from the age of 5 children show selective trust
in others' promises using prosociality, promise keeping, or both to inform their
judgments.
PMID- 29959767
TI - Emotional Over- and Undereating in Children: A Longitudinal Analysis of Child and
Contextual Predictors.
AB - Eating more or eating less in response to negative emotions, called emotional
over- and undereating, is common in children, but research on the etiology of
these behaviors is in its infancy. Drawing on a large, representative community
sample of Norwegian children followed up on a biennial basis from 6 to 10 years
of age (analysis sample: n = 802), child and contextual predictors (i.e., child
temperament, depression symptoms, serious life events, family functioning,
parental sensitivity and structuring) of change in emotional over- and
undereating were examined. Results revealed that low (temperamental) soothability
and less parental structuring at age 6 predicted increased emotional overeating
at age 10 and that lower family functioning at age 6 predicted more emotional
undereating during the same period.
PMID- 29959768
TI - A nonsequential approach to the study of operant renewal: a reverse translation.
AB - ABA renewal is a model of treatment relapse that describes the recurrence of
severe problem behavior when behavior learned in one context (e.g., home; A) and
treated in a separate context (e.g., clinic; B) reemerges when the original
context is reintroduced (A). However, in the typical environment and during the
usual course of treatment for severe problem behavior, the target behavior is
exposed to the baseline context periodically (e.g., the child returns home after
several hours in a clinic setting). Due to the difficulty of studying what effect
this may have on treatment relapse during ABA renewal in a strictly applied
investigation, we developed a human-laboratory translation to study renewal in a
nonsequential manner. Using undergraduate students as subjects, we directly
compared levels of recurrence using the standard ABA renewal procedure and a
modified nonsequential ACA procedure, one modeled from the typical course of
treatment for problem behavior. Both methods produced renewal at comparable
levels, and patterns during nonsequential ACA renewal were similar to those
during sequential ABA renewal. We discuss the implications of these findings in
the framework of treatment for severe problem behavior.
PMID- 29959769
TI - Characterization of obstetric patients with sepsis identified by two diagnostic
scales at a fourth-level clinic in Colombia.
AB - OBJECTIVE: To compare the characterization of an obstetric population diagnosed
with sepsis using systemic inflammatory response syndrome (SIRS) criteria and
sepsis-related organ failure assessment (SOFA). METHODS: The present
retrospective observational descriptive study was conducted at a fourth-level
clinic in Colombia among pregnant women who met the inclusion criteria (two SIRS
criteria plus infection) between January 1, 2015, and December 31, 2016. Patients
with systemic compromise were admitted to the high-complexity obstetric unit
(HCOU), whereas those with multiorgan dysfunction were admitted to the intensive
care unit (ICU). The SIRS scale was deemed positive if all four criteria were
met. A SOFA score of at least 2 was considered a positive result. RESULTS: The
study included 688 patients. The SIRS test at admission was positive among 431
patients (62.6%); 279 (64.7%) in the HCOU group and 152 (35.2%) in the ICU group.
The SOFA test at admission was positive in 69 (38.5%) of 179 patients with
complete data. The concordance-measured using the kappa statistic-between SIRS
and SOFA was low (0.016). CONCLUSION: Using the SIRS scale could promote early
sepsis management by identifying patients who require admission to the HCOU or
ICU; however, low concordance between the SIRS and SOFA results suggested a need
to create diagnostic scales specifically for the obstetric population.
PMID- 29959770
TI - Immune response in goats vaccinated with thiol-binding proteins from Haemonchus
contortus.
AB - The experimental protocol of immunization tested here confirms its protective
effect against Haemonchus contortus in goats. This protection translated into a
65.5% mean reduction in adult worm burden after a homologous challenge, and a
significant decrease (73.2%) in cumulative faecal egg counts (FECs). These
parasitological findings were consistent with the levels of some biopathological
parameters. Thus, the reduction in adult worms and FEC observed in immunized
animals were associated with increased levels of packed cell volume as well as
plasma proteins. This response seems to be related to an important increase in
specific antibodies (in serum and gastric mucus) and eosinophilia in response to
challenge. At the local level, a cellular response was also observed in which
CD4+ lymphocytes and globule leucocytes played a predominant role. Finally, it
should be noted that the study of immunolocalization of proteins used in the
vaccination trial suggests that these antigens have an internal location (at
intestinal and reproductive tissues) in the adult worm. This observation, in
conjunction with the kinetics of specific antibody levels after the challenge,
suggests that these antigens may be part of excretory/secretory (E/S) products.
PMID- 29959771
TI - Correction of severe beam-hardening artifacts via a high-order linearization
function using a prior-image-based parameter selection method.
AB - PURPOSE: Polychromatic x-rays are used in most computed tomography scanners. In
this case, a beam-hardening effect occurs, which degrades the image quality and
distorts the shapes of objects in the reconstructed images. When the beam
hardening artifact is not severe, conventional correction methods can reduce the
artifact reasonably well. However, highly dense materials, such as iron and
titanium, can produce more severe beam-hardening artifacts, which often cannot be
corrected by conventional methods. Moreover, when the size of the metal is large,
severe darks bands due to photon starvation as well as beam-hardening are
generated. The purpose of our study was to develop a new method for correcting
severe beam-hardening artifacts and severe dark bands using a high-order
polynomial correction function and a prior-image-based linearization method.
METHODS: The initial estimate of an image free of beam-hardening (a prior image)
was constructed from the initial reconstruction of the original projection data.
Its corresponding beam-hardening-free projection data (a prior projection) were
calculated by a projection operator onto the prior image. A new beam-hardening
correction function G(praw ) with many high-order terms was effectively
determined via a simple minimization process applied to the difference between
the original projection data and the prior projection data. Using the determined
correction function G(praw ), a corrected linearized sinogram pcorr can be
obtained, which became effectively linear for the line integrals of the object.
Final beam-hardening corrected images can be reconstructed from the linearized
sinogram. The proposed method was evaluated in both simulation and real
experimental studies. RESULTS: All investigated cases in both simulations and
real experiments showed that the proposed method effectively removed not only
streaks for moderate beam-hardening artifacts but also dark bands for severe beam
hardening artifacts without causing structural and contrast distortion.
CONCLUSIONS: The prior-image-based linearization method exhibited better
correction performance than conventional methods. Because the proposed method did
not require time-consuming iterative reconstruction processes to obtain the
optimal correction function, it can expedite the correction procedure and
incorporate more high-order terms in the linearization correction function in
comparison to the conventional methods.
PMID- 29959772
TI - An unusual case of Herlyn-Werner-Wunderlich syndrome with a complete septate
uterus and complicated urinary tract with rare ectopic ureteral opening.
PMID- 29959773
TI - Evaluating competing activities to enhance functional communication training
during reinforcement schedule thinning.
AB - Arranging periods in which requests for reinforcement are denied in a multiple
schedule may result in increased destructive behavior during these periods for
individuals who receive functional communication training (FCT) as treatment for
severe destructive behavior. Providing access to competing activities during
periods of reinforcer unavailability has been shown to minimize destructive
behavior. We evaluated methods to identify effective competing activities for use
when thinning reinforcement availability in a multiple schedule and compared
competing activities embedded within the multiple schedule using an alternating
treatments design. Results suggested at least one competing activity facilitated
favorable treatment outcomes for each participant. We discuss building on this
empirical approach to identify effective competing activities for use during
reinforcement schedule thinning.
PMID- 29959774
TI - Sleeping with the enemy: introgressive hybridization in two invasive
centrarchids.
AB - Introgressive hybridization between Micropterus dolomieu and Micropterus
salmoides was assessed in their invaded South African range using nine
microsatellite markers and two mtDNA gene regions. Although M. dolomieu and M.
salmoides are distantly related, indicated by the large uncorrected pairwise
distances observed between the two species, mitochondrial introgression and
unidirectional admixture was detected.
PMID- 29959775
TI - Short contact with nickel causes allergic contact dermatitis: an experimental
study.
AB - BACKGROUND: Knowledge about the required duration of exposure for elicitation of
allergic nickel dermatitis in nickel-allergic individuals is limited. However, it
often has been proposed that short skin contact is safe. OBJECTIVES: To examine
whether repeated skin contact with nickel over short time periods (3 * 10 min)
can elicit allergic nickel dermatitis. METHODS: Sixteen nickel-allergic adults
and 10 controls were exposed to, respectively, nickel- and aluminium-containing
discs on each volar forearm and on each earlobe for 3 * 10 min. One arm was
pretreated for 24 h with sodium lauryl sulfate (SLS) 0.5% under occlusion before
exposure. One aluminium and one nickel exposure site were clinically evaluated,
and blood flow was measured with laser Doppler flowmetry at day 2 and day 4.
RESULTS: Ten of 16 (63%) nickel-allergic participants developed allergic nickel
dermatitis on SLS-pretreated arm skin and three of 16 (19%) developed it on
normal skin on the earlobe. On the SLS-pretreated arms of nickel-allergic
participants, blood flow increased significantly more on the nickel-exposed skin
than on the aluminium-exposed skin on days 2 and 4. No change in clinical
reactivity or blood flow was found on normal forearm skin in nickel-allergic
participants or on any skin in controls. CONCLUSIONS: This experimental study
showed that relatively short repeated skin contact (3 * 10 min) with metallic
nickel elicits allergic nickel dermatitis in irritated skin and at sites with
previous dermatitis. The results support the restrictions in current nickel
regulation.
PMID- 29959776
TI - Tracking the Within-Trial, Cross-Trial, and Developmental Dynamics of Cognitive
Control: Evidence From the Simon Task.
AB - Six- to 8-year-olds, 10- to 12-year-olds, and adults (N = 108) performed the
Simon task by reaching to targets on a digital display. The spatial and temporal
characteristics of their movements were used to assess how two key processes
underlying cognitive control-a threshold adjustment process and a controlled
selection process-unfold over the course of a response (within-trial dynamics),
are modulated by recent experience (cross-trial dynamics), and contribute to age
related gains in control (developmental dynamics). The results indicate that the
controlled selection process undergoes a more protracted development than the
threshold adjustment process. The results also shed light on a prominent debate
concerning the cross-trial dynamics of control by supporting the feature
integration account over the conflict adaptation account.
PMID- 29959777
TI - Young Children's Theory of Mind Predicts More Sharing With Friends Over Time.
AB - Children (predominantly white and middle class) between 3 and 6 years (M = 55.12
months, N = 145 at Time 1, N = 102 at Time 2) participated in the prosocial
choice test at two time points approximately 10 months apart. Children could
share with strangers, close friends, nonfriends, and in a control, no recipient
condition. Children shared more rewards with friends over time. Age interacted
with recipient type such that older children had a higher probability of
prosocial allocations toward friends and strangers compared to younger children.
Theory of mind (ToM) predicted more prosocial allocations to friends over time,
and the youngest children with higher ToM scores showed the largest increase in
sharing with friends over time.
PMID- 29959778
TI - Evidence on radiation dose reduction using rectangular collimation: a systematic
review.
AB - BACKGROUND: The goal of an intraoral radiograph is to be a valuable diagnostic
tool while keeping the radiation exposure dose as low as reasonably achievable.
The International Commission on Radiological Protection (ICRP) has strong
recommendations for patient dose-reduction strategies. OBJECTIVE: To answer the
following research question: 'In either patient or in phantoms, does rectangular
collimation compared with other forms of collimation reduce the radiation
absorbed dose during intraoral imaging?' METHODS: The search strategy was
developed specifically for each electronic database. Information was collected
from MEDLINE, all EBM Reviews including the Cochrane Library, EMBASE, LILACS,
PubMed and Web of Science, and from a search of the grey literature via Google
Scholar. Studies were included if they reported the radiation dose in intraoral
imaging using rectangular collimation compared with any other type of collimation
or the absence of it. Studies that did not involve comparison/control groups were
excluded. A qualitative appraisal of the included studies was performed. The
Methodological Index for NOn-Randomised Studies (MINORS) tool assessed the
potential risk of bias among the studies, while the Grading of Recommendations,
Assessment, Development and Evaluation (GRADE) approach determined the level of
available evidence. RESULTS: Thirteen studies using different types of receptors,
including D-speed film, E-speed film, phosphor storage plates (PSP) and direct
digital sensors, were included. Different methods to access absorbed and
effective dose by exploring distinct technical parameters, such as distance
object-receptor, long- and short-cone, kVp and mA, exposure time and beam
filtering, were used. High heterogeneity between the studies was found. The level
of evidence was classified as moderate. The radiation dose reduction ranged from
40% to 92% compared with circular collimation. The limitations of the cross
sectional design and in vivo studies were discussed. As this systematic review
applied validated tools and guidelines designed for population-based studies, the
application for studies based on computer simulations and dosimetry measurements
was challenging. CONCLUSION: There is moderate evidence suggesting that
rectangular collimation significantly reduces radiation dose when compared with
round collimation, justifying its implementation in clinical settings/private
practices while taking intraoral radiographs.
PMID- 29959779
TI - Cooperative responding in rats maintained by fixed- and variable-ratio schedules.
AB - The present study investigated the effects of fixed-ratio (FR) and variable-ratio
(VR) reinforcement schedules on patterns of cooperative responding in pairs of
rats. Experiment 1 arranged FR 1, FR 10, and VR 10 schedules to establish
cooperative responding (water delivery depended on the joint responding of two
rats). Cooperative response rates and proportions were higher under intermittent
schedules than under continuous reinforcement. The FR 10 schedule generated a
break-and-run pattern, whereas the VR 10 schedule generated a relatively high and
constant rate pattern. Experiment 2 evaluated the effects of parametric
manipulations of FR and VR schedules on cooperative responding. Rates and
proportions of cooperative responding generally increased between ratio sizes of
1 and 5 but showed no consistent trend as the ratio increased from 5 to 10.
Experiment 3 contrasted cooperative responding between an FR6 schedule and a
yoked control schedule. Coordinated behavior occurred at a higher rate under the
former schedule. The present study showed that external consequences and the
schedules under which the delivery of these consequences are based, select
patterns of coordinated behavior.
PMID- 29959780
TI - Performance characterization of an integrated cone-beam CT system for dedicated
gamma radiosurgery.
AB - PURPOSE: This work describes the performance characterization of a cone-beam CT
guided radiosurgery device, the Gamma Knife(r) IconTM. METHODS: The performance
tests have been categorized into: (a) image quality and mechanical integrity; (b)
image coregistration fidelity; (c) adaptive treatment delivery quality; (d) high
definition motion management performance characterization; (e) software
communication performance testing of the integrated cone-beam CT (CBCT) system.
RESULTS: All image quality performance characterization satisfied or exceeded
manufacturer specifications. The image quality and mechanical stability of the
CBCT system over a 3-month period was within tolerance with negligible (<0.1
degrees ) detector tilt angle. The CBCT definition of the stereotactic space had
a measured average discrepancy of 0.15-0.16 mm in x, y, and z directions. On
average, the high definition motion management system performance was within 0.05
mm with a residual offset of 0.15 mm when large displacements in a given
direction were taken. The adaptive treatment delivery component as measured with
CBCT coregistration of daily setups against reference setup images was accurate
to within 0.2 degrees . Comprehensive end-to-end testing showed a total
uncertainty of better than 0.2 mm in positioning and 0.4% in dosimetry for
treatment of centrally located lesions. CONCLUSIONS: A set of system performance
characterization tests spanning all aspects of the Gamma Knife Icon are
presented. Overall, the system performance was in line with manufacturer
specifications.
PMID- 29959781
TI - Persistent sex disparities in implantable cardioverter-defibrillator therapy.
AB - BACKGROUND: Clinical guidelines recommend cardioverter defibrillator implantation
for patients with heart failure and reduced ejection fraction. Despite this,
women and minorities have been less likely to receive implantable cardioverter
defibrillator (ICD) therapy than white men. We examined race and sex differences
in ICD implantation in a recent cohort. METHODS: Using cross-sectional,
retrospective analyses, we mined our health system's outpatient electronic
medical records to assess age, race, sex, medications, and comorbidities for
patients aged >=18 years with ejection fraction <= 35% during 2014. While
adjusting for confounding variables such as medications, age, and comorbidities,
we conducted a multivariable logistic regression assessing whether racial and sex
differences in ICD therapy persist. RESULTS: Among 5,156 outpatients with
ejection fraction <=35%, 1,681 (32.6%) patients had an ICD present at the time of
their index outpatient visit in 2014. Women were less likely to have an ICD than
men (25.0% vs 36.3%, P < 0.01), and black patients were less likely to have an
ICD than white patients (28.0% vs 33.2%, P = 0.02). In adjusted multivariable
analyses, women were less like to have ICDs (adjusted odds ratio [OR] = 0.68,
95% confidence interval [CI], 0.58-0.79, P < 0.01) but the race difference
dissipated (adjusted OR for black race = 0.86, 95% CI, 0.68-1.08, P = 0.18).
CONCLUSIONS: In this large, outpatient cohort, we have shown that sex differences
in ICD therapy continue to exist, but the difference in ICD prevalence by race
was attenuated. Dedicated studies are required to fully understand the causes of
persistent sex differences in ICD therapy.
PMID- 29959782
TI - Crossroads or "Flyovers" novel insights into ventricular tachycardia mechanisms:
The path is twisting.
AB - Diverging channels of activation may be observed in some ventricular tachycardia
(VT) using ultra-high-density mapping. We present here cases of such diverging
activation patterns as observed from 60 consecutive VT activation maps using the
Rhythmia systemTM (Boston Scientific, Marlborough, MA, USA). Diverging directions
of activation in the same area with "crossroads" or "flyover" pattern can be
traced, implying recording of independent multilayer channels. Adaptation of
current automated recording by the 3D mapping system is mandatory for better
investigating this phenomenon.
PMID- 29959783
TI - The knowledge, attitude and practice of health practitioners towards antibiotic
prescribing and resistance in developing countries-A systematic review.
AB - WHAT IS KNOWN AND OBJECTIVE: Inappropriate antibiotic use is the leading cause of
antibiotic resistance especially in developing countries, where patient
management is mainly based on the prescription of medicines due to deficiencies
in diagnostic procedures. The objective of this study was to conduct a systematic
review of studies on knowledge, attitude and practice of health practitioners
towards antibiotic prescribing and resistance in developing countries. METHODS:
We used MEDLINE and EMBASE to conduct a systematic search for studies. We
included papers that focused on health practitioners' knowledge on antibiotic
use, local resistance and extent of the antibiotic resistance problem; the health
practitioners' confidence in prescribing; commonly used guides; and
recommendations to improve antibiotic prescribing. Studies that assessed other
indicators were excluded. We assessed the quality of the individual studies using
a previously published quality assessment tool. Data were summarized into
proportions and means. We registered the review with PROSPERO, registration
number CRD42018085664. RESULTS AND DISCUSSION: We obtained 384 papers, 345 papers
after deduplication, 28 relevant papers upon reviewing titles and abstracts, and
15 articles fulfilled our inclusion criteria upon full-text review. Most of the
studies were of medium quality (ten), three were of low quality, and two were of
high quality. An average of 80.9% of respondents correctly answered questions
relating to antibiotic use, whereas 39.6% were aware of the local resistance
patterns in their health facilities. Participants stated that antibiotic
resistance was a general problem (75.2%), a global problem (84.7%), a national
problem (88.0%), a problem in their health facilities (71.9%) and a problem in
their daily practice (71.7%). Up to 78.2% of the participants reported that they
were very confident or confident in antibiotic prescribing. WHAT IS NEW AND
CONCLUSION: There was a high reported proportion of participants with an
apparently good level of knowledge on antibiotic use and a high level of
confidence in antibiotic prescribing, but the reported level of knowledge on
local antibiotic resistance was low. The analysis was limited by the low number
of studies included, and most of them had a medium quality.
PMID- 29959784
TI - Rosacea-like demodicosis (but not primary demodicosis) and papulopustular rosacea
may be two phenotypes of the same disease - a microbioma, therapeutic and
diagnostic tools perspective.
PMID- 29959785
TI - Repurposing medications for use in treating HIV infection: A focus on valproic
acid as a latency-reversing agent.
AB - WHAT IS KNOWN AND OBJECTIVE: Combined antiretroviral therapy (ART) reduces human
immunodeficiency virus type 1 (HIV-1) RNA plasma levels below the limit of
detection. However, HIV-1 persists in latently infected CD4+ T cells, which is
currently the barrier to curing HIV-1. Novel mechanisms are being explored to
target HIV-1 latent reservoirs. The purpose of this review was to critically
evaluate the available literature on innovative use of valproic acid (VPA) for
the agent's therapeutic effects on reversing latent human immunodeficiency virus
(HIV) reservoirs. METHODS: A search of PubMed (1996-December 2017) and
International Pharmaceutical Abstracts (1970-December 2017) was conducted using
the MeSH terms HIV, valproic acid and latency. Free text searches included the
terms latency-reversing agents, HIV therapy and valproic acid. RESULTS: Six
clinical trials and one case report were critically evaluated on VPA's
therapeutic effects on reversing HIV reservoirs. Only one study reported that VPA
therapy has a significant effect on reversing HIV-1 latent reservoirs; all other
studies reviewed and did not demonstrate an appreciable effect of VPA on
reversing HIV latent reservoirs. WHAT IS NEW AND CONCLUSION: Current literature
does not support the use of VPA as adjunctive therapy to reverse HIV-1 latent
reservoirs. Sample sizes were small, and overall studies were not sufficiently
powered. Further studies are needed to make informed conclusions on the use of
VPA as an HIV-1 latency-reversing agent.
PMID- 29959786
TI - Does ivacaftor interfere with the antimicrobial activity of commonly used
antibiotics against Pseudomonas aeruginosa?-Results of an in vitro study.
AB - WHAT IS KNOWN AND OBJECTIVE: Ivacaftor is a novel potentiator of defective cystic
fibrosis transmembrane conductance regulator (CFTR) protein, which corrects the
gating defect and increases ion-function of activated cell-surface CFTR. Bacteria
also regulate their physiology through ion channels. However, little is known
about the potential effects of ivacaftor on bacterial ion channels, which, in
turn, may have a potential effect on transport across the bacterial cell
membrane. Therefore, any change in the ability to transport molecules across cell
membranes in bacteria could have an important impact on bacterial transport
physiology. One area where this could be particularly important is in the
movement of antibiotics, both into and out of the bacterial cell. An in vitro
study was therefore performed to examine the influence of ivacaftor at
therapeutic concentration on antibiotic susceptibility of 11 commonly used anti
pseudomonal antibiotics against a population of clinical Pseudomonas aeruginosa
[PA], from CF and non-CF sources. METHOD: Pseudomonas aeruginosa (n = 80;
including 70 ivacaftor-naive clinical PA from sputa from adult CF patients and 10
control PA from non-CF clinical blood culture sources) were examined. Antibiotic
susceptibility was determined by standard disc diffusion assay using CLSI
criteria and measuring zone size (mm), against four classes of anti-pseudomonal
antibiotics, including beta-lactams (temocillin, ceftazidime,
piperacillin/tazobactam, imipenem, meropenem and aztreonam), aminoglycosides
(gentamicin, tobramycin, amikacin), fluoroquinolone (ciprofloxacin) and polymyxin
(colistin), in the absence and presence of ivacaftor (5 MUmol/L), as previously
determined. In addition, all CF and non-CF PA were examined phenotypically in
vitro, as previously described, for changes linked to bacterial virulence,
including (i) growth density (ii) pigmentation, (iii) presence of adhesins and
(iv) change to mucoidy, in the presence/absence of ivacaftor at therapeutic
concentration. RESULTS AND DISCUSSION: Antibiotic susceptibility did not decrease
significantly with any of the antibiotics examined with CF PA isolates or with
non-CF PA control organisms. There was a statistically significant increase in
zone size (CF PA and amikacin, gentamicin, temocillin and ciprofloxacin; Non-CF
PA and amikacin, gentamicin and aztreonam). However, at a population level, this
did not translate into a shift in CLSI category to a more susceptible phenotype.
None of the PA isolates examined were susceptible to ivacaftor alone, and
additionally, no changes were noted with the four phenotypic parameters examined
in the presence of ivacaftor. WHAT IS NEW AND CONCLUSION: This study showed that
antibiotic susceptibility of commonly used anti-pseudomonal antibiotics was not
negatively affected by ivacaftor, in a population of ivacaftor-naive P.
aeruginosa.
PMID- 29959787
TI - Effect of single and multiple doses of elobixibat, an ileal bile acid transporter
inhibitor, on chronic constipation: A randomized controlled trial.
AB - AIMS: Elobixibat is a minimally absorbed ileal bile acid transporter inhibitor.
This study aimed to investigate the safety, tolerability, efficacy,
pharmacokinetics and pharmacodynamics of elobixibat in Japanese patients with
chronic constipation. METHODS: This study consisted of single-dose and multiple
dose tests with a dose-escalating design. Sixty patients including females and
males were randomized into five dose levels of elobixibat (2.5, 5, 10, 15 or 20
mg, n = 10 per level) and corresponding placebo (n = 2 per group). A crossover
design was used to examine food effect in single-dose test. Patients received
test tablets once daily for 14 days in multiple-dose test. We assessed
pharmacokinetic-dose proportionality, levels of serum high- and low-density
lipoprotein cholesterol and plasma 7alpha-hydroxy-4-cholesten-3-one (C4), food
effect and sex-specific effect. Adverse events and bowel functions such as bowel
movements, stool consistency and straining were also evaluated. RESULTS: Food
consumption reduced systemic exposure by around 80% [e.g. least squares mean
(ratio of breakfast/no breakfast) maximum plasma concentration: 0.2085 (90%
confidence interval, 0.1371-0.3172) at 15 mg] while increased plasma C4 level (P
< 0.001). In the multiple-dose test, elobixibat reduced low-density lipoprotein
cholesterol and increased C4 whilst unaltering high-density lipoprotein
cholesterol level. The increased spontaneous bowel movement frequency was
correlated with higher dosage and higher C4 level (R2 = 0.5929 at Week 2).
Adverse events were mainly gastrointestinal symptoms, most of which were mild.
CONCLUSIONS: Elobixibat should be taken before breakfast. Once-daily
administration of elobixibat was found to be safe and tolerated up to 20 mg in
female and male patients with chronic constipation.
PMID- 29959788
TI - Atypical variant of trigeminal trophic syndrome successfully treated with
pregabalin: a case report series.
PMID- 29959789
TI - Dermatology: more than an outpatient specialty.
PMID- 29959790
TI - Development and evaluation of armored RNA-based standards for quantification of
BCR-ABL1p210/p190 fusion gene transcripts.
AB - BACKGROUND: Standards play an important role in detection of the BCR-ABL1 fusion
gene (FG) transcript. However, the standards widely used in laboratories are
mainly based on plasmids or cDNA, which cannot accurately reflect the process of
RNA extraction and cDNA synthesis. Therefore, we aimed to develop armored RNA
based standards for p210 and p190 BCR-ABL1FG transcripts' quantification.
METHODS: Using overlapping polymerase chain reaction (PCR) technology, we first
linked a segment of the p210 or p190 BCR-ABL1FG transcript with four control
genes (CGs; ABL1, BCR, GUSB, and B2M) to form p210FG-CG and p190FG-CG.
Subsequently, using armored RNA technology, we prepared p210FG-CG- and p190FG-CG
armored RNAs and the p210FG-CG and p190FG-CG standards, the values of which were
assigned by digital PCR (dPCR). RESULTS: The p210FG-CG and p190FG-CG standards
were stable and homogeneous, and were significantly linear with r2 > 0.98. A
field trial including 52 laboratories across China showed that the coefficient of
variation (CV%) of BCR-ABL1 values among samples was in the range of 58.6%-129.6%
for p210 samples and 73.2%-194.0% for p190 samples when using local standards. By
contrast, when using the p210FG-CG and p190FG-CG standards, the CV% of BCR-ABL1
values was decreased to 35.6%-124.9% and 36.6%-170.6% for p210 and p190 samples,
respectively. In addition, 33.3% (3/9) of the p210 and p190 samples had CV%
values <50.0%, whereas 44.4% (4/9) and 77.8% (7/9) of the samples had lower CV%
values when using the p210FG-CG and p190FG-CG standards. CONCLUSION: The overall
variability of detection of BCR-ABL1 transcripts decreased significantly when
using the p210FG-CG or p190FG-CG standards, especially the p190FG-CG standard.
PMID- 29959791
TI - eCG stimulation in domestic cats increases the expression of gonadotrophin
induced genes improving oocyte competence during the non-breeding season.
AB - The objective of this study was to evaluate the eCG stimulation on domestic cat
oocyte competence during the non-breeding season. Four experimental groups were
made: (a) untreated cycling cats (Breeding season group; BS), (b) untreated
anestrous cats (Non-breeding group; NB), (c) anestrous cats treated with 200 IU
of eCG (eCG group) and (d) anestrous cats treated with 200 IU of eCG and 100 IU
of hCG four days later (hCG group). In the BS, NB and eCG groups, grade I and II
immature cumulus-oocyte complexes (COCs) were subjected to in vitro maturation or
used for the gene expression analysis of FSHR, LHCGR, EGFR, EGR1, ESR2, PTGS2,
GDF9, BMP15 and GATM. The in vitro matured oocytes from the BS, NB and eCG groups
and the in vivo matured oocytes from the hCG group were subjected to
parthenogenetic activation. The grade I and II COCs from the eCG group had an
increased expression of FSHR, LHCGR, EGFR, EGR1 and ESR2 and a higher maturation
rate than the BS and NB groups (p < 0.05). After parthenogenetic activation, the
blastocyst rate from the hCG, eCG and BS groups was higher than the NB group (p <
0.05). However, no significant improvement was observed in the blastocyst rate in
the hCG group compared to the eCG group (p > 0.05). In conclusion, the eCG
treatment increases the expression of specific genes improving the oocyte
competence during the cat non-breeding season, which is reflected in an enhanced
in vitro maturation and in vitro embryo development after parthenogenetic
activation.
PMID- 29959792
TI - Barriers to active self-management following treatment for head and neck cancer:
Survivors' perspectives.
AB - OBJECTIVE: Active self-management practices may help head and neck cancer (HNC)
survivors to deal with challenges to their physical, functional, social, and
psychological well-being presented by HNC and its treatment. This study
investigates the factors perceived by HNC survivors to act as barriers to their
active self-management following primary treatment. METHODS: In this qualitative
study, 27 HNC survivors identified through 4 designated cancer centres in Ireland
participated in face-to-face semistructured interviews. Interviews were audio
recorded, transcribed, and analysed using thematic analysis. RESULTS: Four themes
(and associated subthemes) describing barriers to survivors' active self
management were identified: emotional barriers (eg, fear of recurrence), symptom
related barriers (eg, loss of taste), structural barriers (eg, access to
appropriate health services), and self-evaluative barriers (eg, interpersonal
self-evaluative concerns). CONCLUSIONS: This is the first study to describe HNC
survivors' views about barriers to their active self-management after treatment.
The findings have important implications for self-management research and
intervention development concerning HNC survivorship.
PMID- 29959793
TI - Haplotype-based association of Vascular Endothelial Growth Factor gene
polymorphisms with urothelial bladder cancer risk in Tunisian population.
AB - BACKGROUND/AIM: Accumulated data suggested that Vascular Endothelial Growth
Factor is a major mediator in vasculogenesis, angiogenesis and recently in
tumorigenesis. Therefore, we aimed to investigate for the first time the
association between VEGF gene variants (-2549I/D (rs35569394), -2578C/A
(rs699947), and +936C/T (rs3025039)) with urothelial bladder cancer (UBC) in
Tunisian population. METHODS: A total of 218 UBC patients and 204 controls were
recruited and genotyped by Polymerase Chain Reaction technique. Odds ratios (OR)
and 95% confidence intervals (CIs) were used to access the association between
the VEGFA gene polymorphisms and UBC. RESULTS: We found a significant decreased
risk association of -2578 C/A polymorphism with UBC (OR (95% CI), 0.62 (0.41
0.94), P = .026) for CA genotype and (OR (95% CI), 0.40 (0.21-0.76), P = .005)
for double homozygous mutant genotype. No associations were found in case of both
polymorphic sites of VEGF, vis. -2549I/D and +936C/T, respectively. Haplotype
analysis revealed a strong linkage disequilibrium between -2578C/A and -2549I/D
and CIC combination is the significant haplotype associated with increased risk
of UBC (OR (95% CI), 3.63 (1.47-8.97), P = .005). Regarding tumor grade/stage and
family history of cancer, no associations were found for -2578C/A polymorphism.
CONCLUSION: CIC haplotype of VEGF gene may be important risk factor for UBC
development in Tunisia.
PMID- 29959794
TI - Titanium dioxide nanoparticles and frontal fibrosing alopecia: cause or
consequence?
PMID- 29959795
TI - Reply to comments on "Perioperative pain management after fibular free flap
harvesting for head-and-neck reconstruction using mini-catheters to inject local
anesthetic: A pilot study".
PMID- 29959796
TI - Reliability of the hidradenitis suppurativa clinical response in the assessment
of patients with hidradenitis suppurativa.
AB - BACKGROUND: Hidradenitis suppurativa clinical response (HiSCR) is a validated
clinical end point for measuring response to treatment in patients with
hidradenitis suppurativa (HS). Previous studies have reported on the validity,
responsiveness and meaningfulness of the HiSCR. OBJECTIVE: To evaluate the HiSCR
for inter- and intrarater reliability characteristics. METHODS: A stand-alone,
two-site, prospective, non-interventional observational study consisted of 22
patients, with self-reported severity between mild, moderate and severe HS. The
Patient Global Impression of Change (PGI-C) scale was completed by patients at
Timepoint 2. Descriptive statistics of Hurley Stage, total abscesses, total
draining fistulas, total inflammatory nodules and total AN count (sum of
inflammatory nodules and lesions) were reported at two timepoints. Inter-rater
reliability and intrarater reliability for the HS lesion count tool were
evaluated at two timepoints (baseline and Day 7) using the HS lesion count tool.
Intraclass correlation (ICC) coefficients of lesion counts were calculated to
evaluate inter- and intrarater reliability of lesion counts between pairs of
dermatologists. RESULTS: The majority of patients demonstrated either no change
or minimally worse PGI-C in HS scores. Descriptive statistics were similar
between rater groups and timepoints assessed. Inter-rater ICC coefficients for
abscess count at Timepoints 1 and 2 were 0.38 and 0.67. The ICC coefficients for
draining fistula and AN count were >=0.61 at both timepoints. In an exploratory
model, ICC coefficients were >=0.68 for all evaluated lesion counts. The test
retest reliability using ICC coefficients was >=0.70 for total abscess, draining
fistula, inflammatory nodule and AN count. CONCLUSION: The HS lesion count tool
had an acceptable inter- and intrarater reliability, indicating that HiSCR has a
strong degree of reproducibility and consistency in the evaluation of patients
with HS.
PMID- 29959797
TI - Performance and validation of a simplified postoperative atrial fibrillation risk
score.
AB - BACKGROUND: Postoperative atrial fibrillation (POAF) occurs in 20-40% patients
who received isolated coronary artery cardiac bypass surgery (CABG). Several POAF
risk prediction models have been developed, but none of them is widely adopted in
practice. Our objective was to derive and validate a simple scoring system to
estimate POAF risk after isolated CABG, using easily available clinical
information. METHODS: Medical records of 1,000 consecutive patients undergoing
isolated CABG were reviewed. The data of first 700 patients were used for model
derivation and data of the remaining 300 patients were used for model validation.
Discrimination and calibration of the newly developed model were assessed.
RESULTS: POAF incidence in both the derivation and validation cohorts was 27.3%.
Age >=65, history of hypertension, heart failure, and myocardial infarction were
independently associated with POAF risk. Risk scores were calculated by summing
weighting points for each independent predictor. The score >=3 was associated
with high POAF incidence (41.1% in the derivation cohort and 44.3% in the
validation cohort). The positive and negative POAF predictive value was 41.1% and
78.5%, respectively, in the derivation cohort, and 44.3% and 80.8%, respectively,
in the validation cohort, when the cut-point score >=3 was used. The Hosmer
Lemeshow goodness-of-fit test P-values were 0.917 and 0.894 in the derivation
cohort and validation cohort, respectively. CONCLUSIONS: This POAF risk following
isolated CABG can be predicted with simple patient characteristic during the
preoperative period. Patients with high risk scores (>=3) may constitute a target
population for POAF prevention and prolonged postoperative surveillance.
PMID- 29959798
TI - Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine
enantiomers in human immunodeficiency virus-infected pregnant women.
AB - AIMS: The present study evaluated the placental transfer and amniotic fluid
distribution of bupivacaine enantiomers in health pregnant women and in human
immunodeficiency virus (HIV)-infected pregnant women receiving epidural
anaesthesia for caesarean section. METHODS: Twelve HIV-infected pregnant women
(HIV group) were treated long-term (at least 8 weeks) with lopinavir/ritonavir
(400/100 mg twice daily), and 12 healthy pregnant women (Control group) who
submitted to epidural anaesthesia with racemic bupivacaine (75 mg) during
caesarean section were investigated. At delivery, samples of maternal and fetal
blood and amniotic fluid were collected (10-20 min after drug administration).
RESULTS: The placental transfer ratio of bupivacaine enantiomers was
significantly higher among the pregnant women from the HIV group when compared
with those from the Control group (Mann-Whitney test, P <= 0.05). Placental
transfer ratios (median and 25th - 75th percentiles) for (+)-(R)-bupivacaine were
0.58 (0.38-0.82) in the HIV group vs. 0.25 (0.18-0.33) in the Control group, and
for (-)-(S)-bupivacaine, they were 0.54 (0.34-0.69) in the HIV group vs. 0.25
(0.19-0.29) in the Control group. The transplacental distribution of bupivacaine
was stereoselective only in the HIV group. The umbilical artery/umbilical vein
ratio and amniotic fluid/maternal vein ratio were low and nonstereoselective, and
no statistically significant differences were observed between the groups.
CONCLUSIONS: This study supports that the placental transfer of both bupivacaine
enantiomers was 100% higher in HIV-pregnant women treated with
lopinavir/ritonavir when compared with that in healthy pregnant women receiving
epidural anaesthesia for caesarean section.
PMID- 29959799
TI - A long-acting pegylated recombinant human growth hormone (Jintrolong(r) ) in
healthy adult subjects: Two single-dose trials evaluating safety, tolerability
and pharmacokinetics.
AB - WHAT IS KNOWN AND OBJECTIVE: Jintrolong(r) is a pegylated recombinant human
growth hormone (rhGH) (PEG-rhGH) developed for weekly subcutaneous (sc)
injection. The current human tolerability trial and pharmacokinetics (PK) trial
evaluated the safety, tolerability and PK of single-dose Jintrolong(r) injection
in healthy adult subjects. METHODS: Both trials were single-centre, randomized,
open-label and single-dose studies. In the human tolerability trial, 34 healthy
subjects were randomized to receive single-dose Jintrolong(r) sc injection (0.01,
0.06, 0.2, 0.5 or 0.8 mg/kg) or placebo. In the PK study, 30 healthy male
subjects were evenly randomized into 3 groups to receive single-dose
Jintrolong(r) sc injection (0.1, 0.2 or 0.4 mg/kg), and the subjects receiving
0.4 mg/kg Jintrolong(r) were given a single sc injection of conventional rhGH
(0.067 mg/kg) after a 14-day washout period. Safety and PK profiles of
Jintrolong(r) were evaluated. RESULTS AND DISCUSSION: Jintrolong(r) was well
tolerated with no serious adverse events or local injection responses. The PK
trial showed that the plasma growth hormone concentration elevated quickly and
stayed at peak level between 12 and 48 hours post-Jintrolong(r) injection, then
decreased gradually back to baseline within 168 hours. Compared to single-dose
conventional rhGH, Jintrolong(r) at all doses demonstrated significantly longer
half time and time to maximum plasma concentration, lower clearance and higher
systemic drug exposure, indicating prolonged presence of GH in the subjects'
circulation. Additionally, systemic exposure to Jintrolong(r) increased in a dose
dependent manner. WHAT IS NEW AND CONCLUSION: Single-dose Jintrolong(r) injection
was well tolerated in healthy adult subjects, and the maximum tolerable dose was
no lower than 0.8 mg/kg. Jintrolong(r) was long-acting with the potential for
weekly administration.
PMID- 29959800
TI - Effects of pearl millet silage ammoniation with urea on carcass and meat quality
of lambs.
AB - This study aimed to evaluate the effect of pearl millet silage ammoniated with
urea on lamb carcass characteristics and meat quality. Thirty-two noncastrated
crossbred lambs at 4-5 months of age, with an average initial body weight of
17.39 +/- 2.16 kg, were distributed into four treatments in a randomized block
experimental design with eight animals per treatment. Experimental diets were
composed of pearl millet silage ammoniated with four levels of urea (0%, 2%, 4%
and 6%, on dry matter basis (DM). Carcass conformation and fatness decreased
linearly (p < 0.05). Except for the fat content, the proximate composition was
not influenced (p < 0.05) by the diets. Meat lightness and yellowness increased
linearly (p < 0.05). There was no effect of diets (p > 0.05) on cooking losses or
shear force. The levels of oleic and erucic fatty acid levels in the meat
decreased linearly (p < 0.05), whereas linoleic and eicosadienoic acids,
polyunsaturated fatty acids, PUFA:SFA ratio and omega6 contents increased (p <
0.05). Pearl millet silage ammoniated with urea allows for the production of good
quality lamb meat, with greater concentrations of polyunsaturated fatty acids.
However, lambs fed diets with pearl millet ammoniated with up to 6% lead to a
reduction of carcass characteristics without significantly affecting loin-eye
area possibly associated with low palatability of the additive used. The lower
acceptance of the silages with higher levels of urea is due to the ammonia
retention in the material is attributed to the ammonization process. Thus, in
spite of the benefits on lamb meat quality, it is suggested that the use of this
additive in the ammonization of tropical forages be carried out with care, in
limits of up to 6%.
PMID- 29959801
TI - Carotid artery wall mechanics in young males with high cardiorespiratory fitness.
AB - NEW FINDINGS: What is the central question of this study? Common carotid artery
(CCA) two-dimensional strain imaging detects intrinsic arterial wall properties
beyond conventional measures of arterial stiffness, but the effect of
cardiorespiratory fitness on two-dimensional strain-derived indices of CCA
stiffness is unknown. What is the main finding and its importance? Two
dimensional strain imaging of the CCA revealed greater peak circumferential
strain and systolic strain rate in highly fit men compared with their less fit
counterparts. Altered CCA wall mechanics might reflect intrinsic training-induced
adaptations that help to buffer the increase in pulse pressure and stroke volume
during exercise. ABSTRACT: The influence of cardiorespiratory fitness on arterial
stiffness in young adults remains equivocal. Beyond conventional measures of
arterial stiffness, two-dimensional strain imaging of the common carotid artery
(CCA) provides new information related to the intrinsic properties of the
arterial wall. Therefore, the aim of this study was to assess the effect of
cardiorespiratory fitness on both conventional indices of CCA stiffness and two
dimensional strain parameters, at rest and after a bout of aerobic exercise in
young, healthy men. Short-axis ultrasound images of the CCA were recorded in 34
healthy men {22 years old [95% confidence interval (CI), 19, 22]} before and
immediately after 5 min of aerobic exercise (40% of maximal oxygen consumption).
Images were analysed for arterial diameter, peak circumferential strain (PCS) and
peak systolic and diastolic strain rates (S-SR and D-SR). Heart rate, systolic
and diastolic blood pressure were simultaneously assessed, and Peterson's elastic
modulus (Ep ) and beta-stiffness (beta1 ) were calculated. Participants were
separated post hoc into moderate- and high-fitness groups [maximal oxygen
consumption, 48.9 (95% CI, 44.7, 53.2) versus 65.6 ml kg-1 min-1 (95% CI, 63.1,
68.1), respectively; P < 0.001]. The Ep and beta1 were similar between groups at
baseline (P > 0.13) but were elevated in the moderate-fitness group postexercise
(P < 0.04). The PCS and S-SR were elevated in the high-fitness group at both time
points [3.0% (95% CI, 1.2, 4.9), P = 0.002, and 0.401 s-1 (95% CI, 0.085, 0.72),
P = 0.02, respectively]. No group differences were observed in CCA heart rate,
systolic or diastolic blood pressure or D-SR throughout the protocol (P > 0.05).
Highly fit individuals exhibit elevated CCA, PCS and S-SR, which might reflect
training-induced adaptations that help to buffer the increase in pulse pressure
and stroke volume during exercise.
PMID- 29959803
TI - Real-life efficacy and safety of secukinumab: results from a tertiary hospital in
Greece.
PMID- 29959802
TI - Pharmacokinetics, metabolism and safety of deuterated L-DOPA (SD-1077)/carbidopa
compared to L-DOPA/carbidopa following single oral dose administration in healthy
subjects.
AB - AIMS: SD-1077, a selectively deuterated precursor of dopamine (DA) structurally
related to L-3,4-dihydroxyphenylalanine (L-DOPA), is under development for
treatment of motor symptoms of Parkinson's disease. Preclinical models have shown
slower metabolism of central deuterated DA. The present study investigated the
peripheral pharmacokinetics (PK), metabolism and safety of SD-1077. METHODS:
Plasma and urine PK of drug and metabolites and safety after a single oral 150 mg
SD-1077 dose were compared to 150 mg L-DOPA, each in combination with 37.5 mg
carbidopa (CD) in a double-blind, two-period, crossover study in healthy
volunteers (n = 16). RESULTS: Geometric least squares mean ratios (GMRs) and 90%
confidence intervals (90% CI) of SD-1077 vs. L-DOPA for Cmax , AUC0-t , and AUC0
inf were 88.4 (75.9-103.1), 89.5 (84.1-95.3), and 89.6 (84.2-95.4), respectively.
Systemic exposure to DA was significantly higher after SD-1077/CD compared to
that after L-DOPA/CD, with GMRs (90% CI) of 1.8 (1.45-2.24; P = 0.0005) and 2.06
(1.68-2.52; P < 0.0001) for Cmax and AUC0-t and a concomitant reduction in the
ratio of 3,4-dihydroxyphenylacetic acid/DA confirming slower metabolic breakdown
of DA by monoamine oxidase (MAO). There were increases in systemic exposures to
metabolites of catechol O-methyltransferase (COMT) reaction, 3-methoxytyramine (3
MT) and 3-O-methyldopa (3-OMD) with GMRs (90% CI) for SD-1077/CD to L-DOPA/CD for
3-MT exposure of 1.33 (1.14-1.56; P = 0.0077) and 1.66 (1.42-1.93; P < 0.0001)
for Cmax and AUC0-t , respectively and GMRs (90% CI) for 3-OMD of 1.19 (1.15,
1.23; P < 0.0001) and 1.31 (1.27, 1.36; P < 0.0001) for Cmax and AUC0-t . SD
1077/CD exhibited comparable tolerability and safety to L-DOPA/CD. CONCLUSIONS:
SD-1077/CD demonstrated the potential to prolong exposure to central DA at
comparable peripheral PK and safety to the reference L-DOPA/CD combination. A
single dose of SD-1077 is safe for further clinical development in Parkinson's
disease patients.
PMID- 29959804
TI - Prevalence and clinicopathological characteristics of lipomatous neurofibromas in
neurofibromatosis 1: An investigation of 229 cutaneous neurofibromas and a
systematic review of the literature.
AB - BACKGROUND: Lipomatous neurofibroma (Lnf) is a histopathological variant with
adipocytes noted among cells of cutaneous neurofibromas. We aimed to investigate
the prevalence and clinicopathological features of Lnfs of neurofibromatosis 1
(NF1)-associated cutaneous neurofibromas and to review the literature
systematically. We also evaluated the expression of leptin (a hormone involved in
lipid metabolism) in neurofibromas to better understand the pathogenesis of Lnfs.
METHODS: A prospective histologic study was conducted on 229 cutaneous
neurofibromas from 85 NF1 individuals. Leptin expression was
immunohistochemically evaluated in 111 cutaneous neurofibromas. To systematically
review the literature, two authors independently performed literature searches
without year restriction. RESULTS: Forty (17.5%) neurofibromas were lipomatous.
Lnfs were significantly larger lesions and associated with females. Eighteen
(7.9%) of all neurofibromas had multinucleated floret-like giant cells, and these
were associated with Lnfs. All neurofibromas expressed leptin. We systematically
reviewed 13 articles. Three large studies investigated Lnfs mainly in sporadic
neurofibromas and suggested that 0.3% to 8.0% of tumors (NF1 and sporadic) are
Lnfs. CONCLUSION: In NF1, Lnfs are common, mainly in larger tumors and women. All
cutaneous NF1-neurofibromas express leptin. It is unknown if the expression of
leptin accounts for the lipomatous variant, but it may have a role in the
pathogenesis of cutaneous neurofibroma.
PMID- 29959805
TI - Methyl donors dietary supplementation to gestating sows diet improves the growth
rate of offspring and is associating with changes in expression and DNA
methylation of insulin-like growth factor-1 gene.
AB - The study aimed to investigate the effects of maternal dietary methyl donors on
the performance of sows and their offspring, and the associated hepatic insulin
like growth factor-1 (IGF-1) expression of the offspring. A total of 24
multiparous sows were randomly fed the control (CON) or the CON diet supplemented
with methyl donors (MD) at 3 g/kg betaine, 15 mg/kg folic acid, 400 mg/kg choline
and 150 MUg/kg VB12 , from mating until delivery. After farrowing, sows were fed
a common lactation diet through a 28-days lactation period and six litters per
treatment were selected to be fed until at approximately 110 kg BW. Maternal MD
supplementation resulted in greater birthweight (p < 0.05) and increased the
piglet weights (p < 0.01) and litter weights (p < 0.05) at the age of day 28,
compared with that in CON group. The offspring pigs in the MD group had greater
ADG (p < 0.05) and tended to lower F:G ratio (p = 0.07) compared with that of CON
group from day 28 to 180 of age. The offspring pigs from MD group had greater
serum IGF-1 concentrations and expressions of hepatic IGF-1 gene and muscular IGF
1 receptor (IGF-1r) protein at birth (p < 0.05), and greater hepatic IGF-1
protein (p = 0.03) and muscular IGF-1r gene expressions (p < 0.05) at slaughter,
than that from the CON group. Moreover, the methylation at the promoter of IGF-1
gene in the liver of newborn piglets and finishing pigs was greater in the MD
group than that of the CON group (p < 0.05). In conclusion, maternal MD
supplementation throughout gestation could enhance the birthweight and postnatal
growth rate of offspring, associated with an increased expression of the IGF-1
gene and IGF-1r, as well as the altered DNA methylation of IGF-1 gene promotor.
PMID- 29959806
TI - Severe bradyarrhythmia linked to left atrial dysfunction in Fabry disease-A cross
sectional study.
AB - BACKGROUND: Fabry disease (FD) is a lysosomal storage disorder caused by an
enzymatic deficiency. Conduction abnormalities and bradyarrhythmias are common
and can occur prior to the onset of left ventricular (LV) hypertrophy. We aimed
to describe the clinical, electrocardiographic and echocardiographic, including
left atrial (LA) function, determinants of bradyarrhythmic events in FD.
HYPOTHESIS: Bradyarrhythmic events are frequent in patients with FD and are
associated with LA dysfunction. METHODS: We designed a cross-sectional study that
includes 53 FD patients (mean age, 45 years; 42% male). Clinical characteristics
and electrocardiographic and echocardiographic data were collected. LA function
was measured using biplane volumes and 2D speckle-tracking echocardiography.
Bradyarrhythmic events were defined as pause of more than 2 seconds (sinus pause
or atrioventricular block) recorded on Holter, severe bradycardia (<= 40 bpm on
ECG) or implantation of a permanent pacemaker. RESULTS: Six (11%) patients had
installation of a pacemaker, 4 (8%) patients had cardiac pause and 2 (4%)
patients had an episode of severe bradycardia. Patients with bradyarrhythmic
events were older and had a lower resting heart rate. On echocardiography, a
significantly higher LV mass, a lower LV ejection fraction, and a more affected
LA reservoir function were found in those with bradyarrhythmic events. Patients
also experienced tachyarrhythmias frequently. Atrial fibrillation occurred in 11
(21%) patients and ventricular tachycardia in 4 (8%) patients. CONCLUSIONS:
Bradyarrhythmia are common manifestations of cardiac involvement in FD. Age, LV
mass, LV ejection fraction and LA reservoir dysfunction can be useful markers
associated with bradyarrhythmia.
PMID- 29959807
TI - Health literacy and the health status of men with prostate cancer.
AB - OBJECTIVE: To test the Health Literacy Questionnaire (HLQ) in a sample of men
with prostate cancer and examine the components of health literacy that are most
strongly associated with mental and physical health-related quality of life in
men with prostate cancer. METHOD: Members (N = 565) of a state-wide prostate
cancer support network in Queensland, Australia (Mage = 71.14, SD = 8.68)
completed the HLQ along with the Medical Outcomes Study, 36-item short-form
health survey (SF-36). Confirmatory factor analysis was employed to assess the
internal structure of the HLQ. The effects (bs) of each of the nine health
literacy factors on mental and physical health status were graphed and compared
using Fishers exact test for comparing parameter estimates. RESULTS: Fit indices
including RMSEA (0.069, CI = 0.066-0.072), CFI (.853), and TLI (.839), alongside
item loadings and internal consistency (Cronbach alphas >0.80) for the nine
factor model, supported the robustness of the HLQ for use in this prostate cancer
sample. Health literacy factors reflecting social and health provider support,
navigating health systems, finding and understanding health information, and
active engagement with providers shared small to moderate associations with
mental health status and little to no association with physical health status.
CONCLUSION: Findings provide support for the use of the HLQ as a valid and
reliable measure of health literacy in men with prostate cancer. Although further
research is required to establish causality, interventions that aim to improve
skills in connecting and effectively communicating with health care services and
providers might lead to better mental health related quality of life for men with
prostate cancer.
PMID- 29959808
TI - Dyadic stress of breast cancer survivors and their caregivers: Are there
differences by sexual orientation?
AB - OBJECTIVE: The objective of the study is to assess dyadic stress among sexual
minority cancer survivor and caregivers compared to heterosexual cancer survivors
and their caregivers. METHODS: We recruited 167 survivors of nonmetastatic breast
cancer of different sexual orientations and their caregivers, who were
interviewed via telephone after obtaining consent. We used inverse propensity
score weighting to account for differences by sexual orientation in age and
length of the survivor-caregiver relationship and simultaneous equation models
consistent with the needs for analyzing dyadic data. RESULTS: Survivors and
caregivers reported stress levels consistent with population norms, irrespective
of survivors' sexual orientation. Accounting for covariates, survivors' and
caregivers' stress did not mutually influence one another overall. However,
differences by sexual orientation were noted such that caregivers' stress was
influential for sexual minority survivors' stress, but not for heterosexual
survivors' stress. CONCLUSIONS: Careful consideration should be given to
caregivers of sexual minority survivors, an underserved group for whom currently
no interventions exist.
PMID- 29959810
TI - The climate, the fuel and the land use: Long-term regional variability of biomass
burning in boreal forests.
AB - The influence of different drivers on changes in North American and European
boreal forests biomass burning (BB) during the Holocene was investigated based on
the following hypotheses: land use was important only in the southernmost
regions, while elsewhere climate was the main driver modulated by changes in fuel
type. BB was reconstructed by means of 88 sedimentary charcoal records divided
into six different site clusters. A statistical approach was used to explore the
relative contribution of (a) pollen-based mean July/summer temperature and mean
annual precipitation reconstructions, (b) an independent model-based scenario of
past land use (LU), and (c) pollen-based reconstructions of plant functional
types (PFTs) on BB. Our hypotheses were tested with: (a) a west-east northern
boreal sector with changing climatic conditions and a homogeneous vegetation, and
(b) a north-south European boreal sector characterized by gradual variation in
both climate and vegetation composition. The processes driving BB in boreal
forests varied from one region to another during the Holocene. However, general
trends in boreal biomass burning were primarily controlled by changes in climate
(mean annual precipitation in Alaska, northern Quebec, and northern Fennoscandia,
and mean July/summer temperature in central Canada and central Fennoscandia) and,
secondarily, by fuel composition (BB positively correlated with the presence of
boreal needleleaf evergreen trees in Alaska and in central and southern
Fennoscandia). Land use played only a marginal role. A modification towards less
flammable tree species (by promoting deciduous stands over fire-prone conifers)
could contribute to reduce circumboreal wildfire risk in future warmer periods.
PMID- 29959809
TI - Phase II study of ceritinib in alectinib-pretreated patients with anaplastic
lymphoma kinase-rearranged metastatic non-small-cell lung cancer in Japan: ASCEND
9.
AB - Clinical experience of ceritinib in patients who progressed on alectinib is
limited. In this prospective phase II study, we evaluated the activity of
ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase (ALK)
rearranged metastatic (stage IIIB/IV) non-small-cell lung cancer (NSCLC) in
Japan. All patients were required to have >=1 measurable lesion per RECIST, 1.1,
and a World Health Organization Performance Status (WHO PS) of 0-1. Prior
crizotinib and/or up to 1 chemotherapy regimen was allowed. Primary endpoint was
investigator-assessed overall response rate (ORR) per RECIST 1.1. Ceritinib was
given at a dose of 750 mg/day fasted. A total of 20 patients were enrolled from
August 2015 to March 2017. All patients received prior alectinib (100%), 13
(65.0%) patients received prior platinum-based chemotherapy, and 4 (20%) patients
received prior crizotinib. Median duration of exposure and the follow-up time
with ceritinib were 3.7 months (range: 0.4-15.1) and 11.6 months (range: 4.8
23.0), respectively. Investigator-assessed ORR was 25% (95% CI: 8.7-49.1). Key
secondary endpoints, all investigator assessed, included disease control rate
(70.0%; 95% CI: 45.7-88.1), time to response (median, 1.8 months; range: 1.8
2.0), and duration of response (median, 6.3 months; 95% CI: 3.5-9.2). Median
progression-free survival was 3.7 months (95% CI: 1.9-5.3). The most common
adverse events reported were diarrhea (85.0%), nausea (80.0%), and vomiting
(65.0%). Based on our findings, ceritinib could be considered as one of the
treatment options for patients with ALK-positive NSCLC who progressed on
alectinib. (Trial registration no. NCT02450903).
PMID- 29959811
TI - Hemoglobin A1c predicts hemorrhagic transformation and poor outcomes after acute
anterior stroke.
AB - BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a major complication
of acute ischaemic stroke that is potentially related to clinical deterioration.
The objective of this study was to assess whether chronic hyperglycemia is a
predictive factor of HT in patients with acute anterior stroke. METHODS: Patients
with acute anterior stroke were included in this study. Hemoglobin A1c (HbA1c)
was measured in the morning after hospitalization. HT was detected by computed
tomography scans or gradient echo magnetic resonance imaging performed 4 (+/-2)
days after onset. Univariate and multivariate logistic regression analyses were
used to assess the risks for HT and short-term outcomes. RESULTS: Of the 426
patients included, 93 (21.8%) had HT: 61 (14.3%) presented with hemorrhagic
infarction and 32 (7.5%) presented with parenchymal hematoma. A total of 54
patients received thrombolytic treatment and 18 (33.3%) were found to have HT. In
the multivariate analysis, HbA1c [odds ratio (OR), 1.294; 95% confidence interval
(CI), 1.097-1.528], infarction size (OR, 3.358; 95% CI, 1.748-6.449) and
thrombolytic therapy (OR, 3.469; 95% CI, 1.757-6.847) were predictors of HT. The
predictive effect of HbA1c on HT was still observed in both groups when patients
were stratified according to the levels of fasting blood glucose. HbA1c was found
to be a predictor of poor outcomes in the multilogistic regression analysis (OR,
1.482; 95% CI, 1.228-1.788). CONCLUSIONS: Higher HbA1c was independently related
to HT and poor neurological outcomes in patients with ischaemic stroke. These
findings have significant implications for the treatment of diabetes and glucose
management in patients with diabetes mellitus and/or acute ischaemic stroke.
PMID- 29959812
TI - A Possible Path to Prebiotic Peptides Involving Silica and Hydroxy Acid-Mediated
Amide Bond Formation.
AB - The formation of alanine and glycine oligomers in films produced by drying
aqueous mixtures of lactic acid and silica nanoparticles has been studied as a
model prebiotic reaction. The addition of silica results in alanine or glycine
enrichment in the polymers. Oligomerization proceeds through ester-mediated
peptide bond formation in an acidic and evaporative environment at temperatures
as low as 85 degrees C. For both amino acids, the dominant species produced in
the presence of silica and lactic acid are rich in amide bonds and deficient in
ester linkages. At higher temperatures, glycine and alanine oligomers contain
only a single hydroxy acid residue conjugated to the peptide N terminus. Similar
product distributions occur with silica particles prereacted with lactic acid,
which suggests the catalytic role of a functionalized surface. This work
highlights the role minerals might have served in transitioning from oligomers
with both ester and amide linkages (depsipeptides) to peptides in a prebiotic
context.
PMID- 29959813
TI - Multiple sclerosis: severe exacerbation after stopping disease-modifying drugs.
PMID- 29959814
TI - Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) vs standard RARP:
it's time for critical appraisal.
PMID- 29959815
TI - High-dose rate intracavitary brachytherapy pretreatment dwell position
verification using a transparent applicator.
AB - PURPOSE: The major errors in HDR brachytherapy are related to treatment distance,
almost all of which are caused by incorrect applicator information. The aim of
this study is to propose a quick pretreatment verification method to evaluate
channel length and dwell position with a transparent applicator, which, in
addition, is suitable as an education tool to assist in the understanding of the
applicator structure. METHODS: A transparent applicator model was fabricated
using a three-dimensional printer and transparent resin. Its aim is to be a
replica of a real gynecological applicator. The pretreatment verification is
performed by observing the planned dwell positions of a check cable inside a
transparent applicator. A digital camera acquired images and the dwell positions
of the radioactive source and check cable were evaluated by comparing them with
respect to the theoretical dwell positions marked by the proper x-ray marker. The
potential effectiveness of verification using a transparent applicator was also
evaluated using brachytherapy events reported in the literature. RESULTS: The
transparent applicator closely resembles the real applicator in shape and had an
error of less than 0.2 mm. The average dwell position displacement between the
radioactive source and check cable was 0.4 mm. The analysis of brachytherapy
events showed that channel-length, dwell-position, and step-size errors made up
50% of all events, but affected 64% of all patients. CONCLUSIONS: The transparent
applicator model enables a noninvasive, repeatable verification of the channel
length and dwell positions to be performed before treatment. This verification
has the potential to help prevent common errors in treatment delivery. In
addition, the transparent applicator model can be used as a teaching tool to help
clinicians understand the operation of the applicator, lowering the risk of
events.
PMID- 29959816
TI - Executive summary of AAPM Report Task Group 113: Guidance for the physics aspects
of clinical trials.
AB - The charge of AAPM Task Group 113 is to provide guidance for the physics aspects
of clinical trials to minimize variability in planning and dose delivery for
external beam trials involving photons and electrons. Several studies have
demonstrated the importance of protocol compliance on patient outcome. Minimizing
variability for treatments at different centers improves the quality and
efficiency of clinical trials. Attention is focused on areas where variability
can be minimized through standardization of protocols and processes through all
aspects of clinical trials. Recommendations are presented for clinical trial
designers, physicists supporting clinical trials at their individual clinics,
quality assurance centers, and manufacturers.
PMID- 29959817
TI - Genetic characterization and epidemiological implications of Campylobacter
isolates from wild birds in South Korea.
AB - In this study, we genotyped Campylobacter isolates from wild birds by multilocus
sequence typing (MLST) and analysed their virulence genes by PCR with the aim to
gain a deeper understanding of the epidemiology of Campylobacter infection.
Amongst 60 Campylobacter isolates from 12 wild bird species, we identified 32
sequence types (STs; 29 STs from Campylobacter jejuni and 3 STs from
Campylobacter coli). Clonal complex 45 (CC-45), was the most common CC (n = 17
isolates), followed by CC-692 (n = 10). ST-137 was the most prevalent (n = 9),
originating from 4 avian species. Eleven C. jejuni STs (37.9%) and 2 C. coli STs
(66.7%) overlapped with those of human clinical origin. Thirteen C. jejuni STs
and all 3 C. coli STs from wild birds were associated with STs of multiple
sources (poultry, livestock and/or the environment). There was a strong
association between wild bird isolates and domestic duck isolates with 7 STs
shared between these host species. There was a high prevalence of all the 11
virulence genes tested in all wild bird isolates, with no association of any ST
to a particular virulence profile. All Campylobacter spp. isolates from wild
birds carried the cadF gene. The cytotoxin-encoding genes cdtB and cdtC were
present in all 7 C. coli isolates, and in 52 (98.1%) and 50 (94.3%) C. jejuni
isolates, respectively. Six C. jejuni isolates carried the wlaN gene, and virB11
was found in 8 isolates. The results of this study show that ST overlap between
human and wild bird isolates frequently occurs, and the high prevalence of
virulence genes in wild bird isolates indicates that wild birds shed
Campylobacter in their faeces that are potentially pathogenic to humans.
PMID- 29959818
TI - Materials Nanoarchitectonics for Mechanical Tools in Chemical and Biological
Sensing.
AB - In this Focus Review, nanoarchitectonic approaches for mechanical-action-based
chemical and biological sensors are briefly discussed. In particular, recent
examples of piezoelectric devices, such as quartz crystal microbalances (QCM and
QCM-D) and a membrane-type surface stress sensor (MSS), are introduced. Sensors
need well-designed nanostructured sensing materials for the sensitive and
selective detection of specific targets. Nanoarchitectonic approaches for sensing
materials, such as mesoporous materials, 2D materials, fullerene assemblies,
supported lipid bilayers, and layer-by-layer assemblies, are highlighted. Based
on these sensing approaches, examples of bioanalytical applications are presented
for toxic gas detection, cell membrane interactions, label-free biomolecular
assays, anticancer drug evaluation, complement activation-related multiprotein
membrane attack complexes, and daily biodiagnosis, which are partially supported
by data analysis, such as machine learning and principal component analysis.
PMID- 29959819
TI - Safety and benefit of using a virtual bolus during treatment planning for breast
cancer treated with arc therapy.
AB - PURPOSE: This study evaluates the benefit of a virtual bolus method for
volumetric modulated arc therapy (VMAT) plan optimization to compensate breast
modifications that may occur during breast treatment. METHODS: Ten files were
replanned with VMAT giving 50 Gy to the breast and 47 Gy to the nodes within 25
fractions. The planning process used a virtual bolus for the first optimization,
then the monitors units were reoptimized without bolus, after fixing the segments
shapes. Structures and treatment planning were exported on a second scanner (CT)
performed during treatment as a consequence to modifications in patient's
anatomy. The comparative end-point was clinical target volume's coverage. The
first analysis compared the VMAT plans made using the virtual bolus method (VB
VMAT) to the plans without using it (NoVB-VMAT) on the first simulation CT. Then,
the same analysis was performed on the second CT. Finally, the level of
degradation of target volume coverage between the two CT using VB-VMAT was
compared to results using a standard technique of forward-planned multisegment
technique (Tan-IMRT). RESULTS: Using a virtual bolus for VMAT does not degrade
dosimetric results on the first CT. No significant result in favor of the NoVB
VMAT plans was noted. The VB-VMAT method led to significant better dose
distribution on a second CT with modified anatomies compared to NoVB-VMAT. The
clinical target volume's coverage by 95% (V95%) of the prescribed dose was 98.9%
[96.1-99.6] on the second CT for VB-VMAT compared to 92.6% [85.2-97.7] for NoVB
VMAT (P = 0.0002). The degradation of the target volume coverage for VB-VMAT is
not worse than for Tan-IMRT: the median differential of V95% between the two CT
was 0.9% for VMAT and 0.7% for Tan-IMRT (P = 1). CONCLUSION: This study confirms
the safety and benefit of using a virtual bolus during the VMAT planning process
to compensate potential breast shape modifications.
PMID- 29959820
TI - Gene expression-based drug repurposing to target aging.
AB - Aging is the largest risk factor for a variety of noncommunicable diseases. Model
organism studies have shown that genetic and chemical perturbations can extend
both lifespan and healthspan. Aging is a complex process, with parallel and
interacting mechanisms contributing to its aetiology, posing a challenge for the
discovery of new pharmacological candidates to ameliorate its effects. In this
study, instead of a target-centric approach, we adopt a systems level drug
repurposing methodology to discover drugs that could combat aging in human brain.
Using multiple gene expression data sets from brain tissue, taken from patients
of different ages, we first identified the expression changes that characterize
aging. Then, we compared these changes in gene expression with drug-perturbed
expression profiles in the Connectivity Map. We thus identified 24 drugs with
significantly associated changes. Some of these drugs may function as antiaging
drugs by reversing the detrimental changes that occur during aging, others by
mimicking the cellular defence mechanisms. The drugs that we identified included
significant number of already identified prolongevity drugs, indicating that the
method can discover de novo drugs that meliorate aging. The approach has the
advantages that using data from human brain aging data, it focuses on processes
relevant in human aging and that it is unbiased, making it possible to discover
new targets for aging studies.
PMID- 29959822
TI - Agility MLC transmission optimization in the Monaco treatment planning system.
AB - The Monaco Monte Carlo treatment planning system uses three-beam model components
to achieve accuracy in dose calculation. These components include a virtual
source model (VSM), transmission probability filters (TPFs), and an x-ray voxel
Monte Carlo (XVMC) engine to calculate the dose in the patient. The aim of this
study was to assess the TPF component of the Monaco TPS and optimize the TPF
parameters using measurements from an Elekta linear accelerator with an AgilityTM
multileaf collimator (MLC). The optimization began with all TPF parameters set to
their default value. The function of each TPF parameter was characterized and a
value was selected that best replicated measurements with the AgilityTM MLC. Both
vendor provided fields and a set of additional test fields were used to create a
rigorous systematic process, which can be used to optimize the TPF parameters. It
was found that adjustment of the TPF parameters based on this process resulted in
improved point dose measurements and improved 3D gamma analysis pass rates with
Octavius 4D. All plans calculated with the optimized beam model had a gamma pass
rate of > 95% using criteria of 2% global dose/2 mm distance-to-agreement, while
some plans calculated with the default beam model had pass rates as low as 88.4%.
For measured point doses, the improvement was particularly noticeable in the low
dose regions of the clinical plans. In these regions, the average difference from
the planned dose reduced from 4.4 +/- 4.5% to 0.9 +/- 2.7% with a coverage factor
(k = 2) using the optimized beam model. A step-by-step optimization guide is
provided at the end of this study to assist in the optimization of the TPF
parameters in the Monaco TPS. Although it is possible to achieve good clinical
results by randomly selecting TPF parameter values, it is recommended that the
optimization process outlined in this study is followed so that the transmission
through the TPF is characterized appropriately.
PMID- 29959821
TI - Resveratrol ameliorates Lewis lung carcinoma-bearing mice development, decreases
granulocytic myeloid-derived suppressor cell accumulation and impairs its
suppressive ability.
AB - Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of
immature myeloid cells which consist of 2 subsets: granulocytic MDSC (G-MDSC) and
monocytic MDSC (M-MDSC). MDSC expand in tumor-bearing hosts and contribute to
immunotherapeutic resistance by remarkably blocking effector T-cell activation
via different mechanisms. Resveratrol (RSV) is a polyphenol and it has been
widely used for its various health benefits. However, the underlying mechanism of
its anti-tumor properties remains unclear. In this study, a transplantable mouse
model was used to investigate the effects of RSV on MDSC. The results showed that
RSV ameliorated tumor development by decreasing G-MDSC accumulation, impairing
its suppressive ability on CD8+ T cells and promoting M-MDSC differentiation into
CD11c+ and F4/80+ cells. Our results indicated that RSV should be considered as a
modular of MDSC suppressive function and that RSV is a novel booster for tumor
immunotherapy.
PMID- 29959823
TI - Gold-Catalyzed Formal C-C Bond Insertion Reaction of 2-Aryl-2-diazoesters with
1,3-Diketones.
AB - The transition-metal-catalyzed formal C-C bond insertion reaction of diazo
compounds with monocarbonyl compounds is well established, but the related
reaction of 1,3-diketones instead gives C-H bond insertion products. Herein, we
report a protocol for a gold-catalyzed formal C-C bond insertion reaction of 2
aryl-2-diazoesters with 1,3-diketones, which provides efficient access to
polycarbonyl compounds with an all-carbon quaternary center. The aryl ester
moiety plays a crucial role in the unusual chemoselectivity, and the addition of
a Bronsted acid to the reaction mixture improves the yield of the C-C bond
insertion product. A reaction mechanism involving cyclopropanation of a gold
carbenoid with an enolate and ring-opening of the resulting donor-acceptor-type
cyclopropane intermediate is proposed. This mechanism differs from that of the
traditional Lewis-acid-catalyzed C-C bond insertion reaction of diazo compounds
with monocarbonyl compounds, which involves a rearrangement of a zwitterion
intermediate as a key step.
PMID- 29959824
TI - Urine cytology is a feasible tool for assessing erythematous bladder lesions
after bacille Calmette-Guerin (BCG) treatment.
AB - OBJECTIVES: To investigate the need to biopsy erythematous lesions of the bladder
after bacille Calmette-Guerin (BCG) treatment as well as the diagnostic value of
voided urine cytology in the detection of recurrence. MATERIALS AND METHODS: Data
on 206 consecutive patients with non-muscle-invasive bladder cancer treated with
one or more BCG instillations in the period 2009-2015 at Satakunta Central
Hospital and Turku University Hospital were reviewed. Biopsy histology was pooled
according to lesion cystoscopy appearance regarding growth pattern and presence
of erythema. Voided urine cytology grading before resection was reviewed. We
correlated the cystoscopy findings with histology and calculated the sensitivity,
specificity, and positive (PPV) and negative predictive value (NPV) for voided
urine cytology. RESULTS: In total, 159 patients with a median follow-up of 35
months were included in the study. Altogether, 367 biopsies were analysed. In the
case of papillary or flat tumours, 76% of biopsies showed malignant histology and
the diagnostic value of cytology was very limited (sensitivity 33%, specificity
84%). Erythematous lesions constituted 57% of all biopsy targets, with the
majority being either chronic non-specific inflammation or granulomatous
inflammation; 10% of erythematous lesions were malignant at pathological
examination. In contrast to papillary and flat tumours, cytology proved to be
more accurate in the case of erythematous lesions with a sensitivity,
specificity, PPV and NPV of 59%, 76%, 23% and 94%, respectively. CONCLUSION:
Bladder lesions after BCG instillations pose a challenge during follow-up and the
appropriate management strategy is not clear. Lesions should not be overlooked as
being BCG-induced irritation because they may harbour significant malignancies.
The presence of papillary or flat tumour always warrants a biopsy or resection.
In the case of erythematous lesions, our results suggest that biopsy may be
avoided if voided urine cytology is negative.
PMID- 29959825
TI - Community- and ecosystem-level effects of multiple environmental change drivers:
Beyond null model testing.
AB - Understanding the joint effect of multiple drivers of environmental change is a
key scientific challenge. The dominant approach today is to compare observed
joint effects with predictions from various types of null models. Drivers are
said to combine synergistically (antagonistically) when their observed joint
effect is larger (smaller) than that predicted by the null model. Here, I argue
that this approach does not promote understanding of effects on important
community- and ecosystem-level variables such as biodiversity and ecosystem
function. I use ecological theory to show that different mechanisms can lead to
the same deviation from a null model's prediction. Inversely, I show that the
same mechanism can lead to different deviations from a null model's prediction.
These examples illustrate that it is not possible to make strong mechanistic
inferences from null models. Next, I present an alternative framework to study
such effects. This framework makes a clear distinction between two different
kinds of drivers (resource ratio shifts and multiple stressors) and integrates
both by incorporating stressor effects into resource uptake theory. I show that
this framework can advance understanding because of three reasons. First, it
forces formalization of "multiple stressors," using factors that describe the
number and kind of stressors, their selectivity and dynamic behaviour, and the
initial trait diversity and tolerance among species. Second, it produces testable
predictions on how these factors affect biodiversity and ecosystem function,
alone and in combination with resource ratio shifts. Third, it can fail in
informative ways. That is, its assumptions are clear, so that different kinds of
deviations between predictions and observed effects can guide new experiments and
theory improvement. I conclude that this framework will more effectively progress
understanding of global change effects on communities and ecosystems than does
the current practice of null model testing.
PMID- 29959826
TI - Construction of Quaternary Stereocenters by Palladium-Catalyzed Carbopalladation
Initiated Cascade Reactions.
AB - The enantioselective synthesis of molecules containing quaternary stereocenters
is a field of intense research interest and development. Among the known organic
transformations, carbopalladation-initiated domino transformations constitutes a
general method for the construction of compounds containing cyclic or spiro
quaternary stereocenters. In this Minireview, recent achievements in palladium
catalyzed domino Heck/C-H functionalizations and developments in enantioselective
carbopalladation-initiated domino processes are summarized.
PMID- 29959827
TI - Coordinate transformation aided finite element method for contour detection of
breast tumors in microwave imaging.
AB - A coordinate transformation based finite element method is presented for
detecting contours of breast cancer tissues in the context of microwave imaging.
The geometry and location of a single or multiple cancerous tumors inside a
breast tissue are identified by constructing an inverse problem based on the
genetic optimization algorithm. The expensive forward solution phase during
repeated cost function evaluations is accelerated by placing a transformation
medium inside the finite element mesh. This allows using a uniform or rectangular
mesh even when irregular tumor geometries are considered. Therefore, the
computational load is reduced. The algorithm is implemented in MATLAB using
parallel programming tools. A realistic numerical breast phantom repository,
which is available in the University of Wisconsin-Madison webpage, is used to
test the algorithm. The performance of the algorithm is also tested by utilizing
the Monte Carlo approach, where the inverse problem is run several times and the
statistical parameters of the runs are determined. Various simulation results are
demonstrated.
PMID- 29959828
TI - Interpopulation Variability in the Essential Oil Composition of Cistus creticus
subsp. eriocephalus from Sardinia.
AB - Cistus genus is widespread in the Mediterranean regions with several species and
is traditionally known as a natural remedy, but few previous phytochemical
researches have been reported on Cistus species growing in Sardinia. The aim of
this work was to study the interpopulation variability of the volatiles of C.
creticus subsp. eriocephalus to find out the natural chemotypes of this taxon for
chemotaxonomic purposes. Plant material was collected from seven wild populations
in Sardinia. The oils from aerial part were obtained by hydrodistillation and
analyzed by GC/MS enabling to identify 185 compounds. The seven samples showed
appreciable variations in their chemical composition. MA was found almost
exclusively linear hydrocarbons (85%) and MN presented fatty acids (36.97%) as
major fraction. CP and MN had high quantity of non-terpenic carbonylic compounds
(63% and 69%, respectively) and in CP was found also sclareol, a well-known
antimicrobial compound. PCA analysis showed the existence of a high
interpopulation variability within the essential oils of C. creticus subsp.
eriocephalus growing in Sardinia. For example, MN and CP are very close to each
other as CG is close to PM. BN is isolated from the others Cistus populations due
to lacking essential oil. These data suggest that the basis of variation in the
volatile composition of seven C. creticus subsp. eriocephalus populations depends
on hybridization and that the sample without essential oil is the only one no
hybridized.
PMID- 29959829
TI - Oral health experiences and needs among young adults after a first-episode
psychosis : a phenomenological study.
AB - : WHAT IS KNOWN ON THE SUBJECT?: Substance abuse, poor lifestyle and side effects
of medication often occur and cause oral health problems in patients diagnosed
with severe mental illness (SMI). Oral health in SMI is related to quality of
life, self-esteem, and daily functioning. Despite its importance, oral health in
mental health care is still a postponed healthcare pathway. Treatment guidelines
on patients after a first episode psychosis (FEP) indicate that interventions are
recommended, but clinical advice is lacking. However, no research on the
experiences of young adults' oral health after FEP has been conducted. WHAT DOES
THIS PAPER ADD TO EXISTING KNOWLEDGE?: This study is the first study to gain
insight into most important experiences in patients after FEP regarding oral
health. After FEP, participants experience many risk factors, for example
substance use, poor diet and financial problems, and participants are not able to
adequately attend to their oral health. There is a lack of awareness among
participants after FEP about oral health and participants do have high burden.
After FEP, participants need support and help from their environment to maintain
their oral health. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: In FEP, oral health
needs more attention to avoid the negative consequences in a later phase of the
illness. To fill the gap between patients' needs regarding oral health care and
the attention of mental healthcare professionals, the awareness of patients and
mental health professionals concerning oral health should be heightened, and
clinical interventions to support these needs should be developed. ABSTRACT:
Introduction Oral health affects quality of life, self-esteem, physical health
and daily functioning. Treatment guidelines on patients after first episode
psychosis (FEP) recommend interventions, but clinical interventions are lacking.
No research on the experiences of young adults' oral health after FEP has been
conducted. Aims This study aimed to explore the lived experiences and needs of
patients after FEP with regard to their oral health. Design and Methods Single
centre phenomenological study using open interviews (N = 30). Data were analysed
using the Colaizzi method. Results Patients reported oral health problems since
their FEP. The problems that patients encountered were dental care in general
(e.g., a lack of awareness), risk factors (e.g., substance use, poor diet and
financial problems), overall experiences with dentists/dental hygienists and the
gap between needs and interventions. Discussion There is a lack of awareness
among patients after FEP about oral health while patients are not able to
adequately attend to their oral health and patients have high burden on this
topic. Implications for mental health nursing To bridge the gap between patients'
needs regarding oral health, the awareness of patients and mental health
professionals should be heightened, and patients should be better supported by
mental health professionals.
PMID- 29959830
TI - The distribution of HLA-DRB3 alleles among HLA-DRB1*03:01-positive haplotypes.
AB - HLA-DRB3 allelic polymorphism on HLA-DRB1*03:01-positive haplotypes was
investigated among 104 cadaveric donors typed for HLA-A, -B, -DRB1, and -DRB3.
Only HLA-DRB3*01:01:02 and -DRB3*02:02:01:01 alleles were detected among HLA
DRB1*03:01-positive individuals and their distribution depended on HLA-B*08
presence: nearly all HLA-B*08-positive samples carried DRB3*01:01:02, while HLA
DRB3*02:02:01:01 was more frequent among HLA-B*08-negative subjects.
PMID- 29959831
TI - Tensor regularized total variation for denoising of third harmonic generation
images of brain tumors.
AB - Third harmonic generation (THG) microscopy shows great potential for instant
pathology of brain tissue during surgery. However, the rich morphologies
contained and the noise associated makes image restoration, necessary for
quantification of the THG images, challenging. Anisotropic diffusion filtering
(ADF) has been recently applied to restore THG images of normal brain, but ADF is
hard-to-code, time-consuming and only reconstructs salient edges. This work
overcomes these drawbacks by expressing ADF as a tensor regularized total
variation model, which uses the Huber penalty and the L1 norm for tensor
regularization and fidelity measurement, respectively. The diffusion tensor is
constructed from the structure tensor of ADF yet the tensor decomposition is
performed only in the non-flat areas. The resulting model is solved by an
efficient and easy-to-code primal-dual algorithm. Tests on THG brain tumor images
show that the proposed model has comparable denoising performance as ADF while it
much better restores weak edges and it is up to 60% more time efficient.
PMID- 29959832
TI - An illustration of human sperm morphology and their functional ability among
different group of subfertile males.
AB - Condensed sperm chromatin is a prerequisite for natural fertilization. Some
reports suggested the prevalence of chromatin condensation defects in
teratozoospermia cases with head anomalies; conversely, earlier studies
exemplified its occurrence in morphologically normal spermatozoa too. The aim of
this study was to compare the condensation defects in correlation with head
anomalies among different groups of subfertile males and its impact on the rate
of fertilization in assisted reproduction procedures. Ultrastructure analysis of
spermatozoa through scanning electron microscopy and atomic force microscopy
could facilitate an in-depth evaluation of sperm morphology. Nuclear condensation
defects (%) in spermatozoa were analyzed in 666 subjects, and its effect on the
rate of fertilization was analyzed in 116 IVF and 90 intracytoplasmic sperm
injection cases. There was no correlation of condensation defects with head
anomalies (%). Student's t-test showed no significant changes in mean values of
condensation defects in abnormal semen samples in comparison with the normal
group. Condensation defects were observed in normal spermatozoa too, which was
negatively associated with the rate of fertilization in IVF (p < 0.01), but
intracytoplasmic sperm injection outcome remained unaffected. Ultrastructure
study revealed sperm morphological features in height, amplitude, and three
dimensional views in atomic force microscopy images presenting surface
topography, roughness property of head, and compact arrangement of mitochondria
over axoneme with height profile at nanoscale. In pathological forms, surface
roughness and nuclear thickness were marked higher than the normal spermatozoa.
Thus, percentage of normal spermatozoa with condensation defects could be a
predictive factor for the rate of fertilization in IVF. From diverse shapes of
nucleus in AFM imaging, it could be predicted that defective nuclear shaping
might be impeding the activity of some proteins/ biological motors, those
regulate the proper Golgi spreading over peri-nuclear theca.
PMID- 29959833
TI - Optimization of laboratory procedures for intrauterine insemination: survey of
methods in relation to clinical outcome.
AB - BACKGROUND: There is a wide practice variation of used methods and outcomes in
IUI in fertility laboratories. Standardization of the IUI procedure is important
for reducing inconsistency among laboratories in counseling infertile couples and
in pregnancy results. The aim of the study was to evaluate the currently used
laboratory procedures of IUI in Dutch fertility laboratories and their effect on
IUI pregnancy results. Additionally, the methods for semen analysis (SA) were
evaluated, as SA is related to IUI in terms of inseminated sperm number and IUI
counseling. MATERIAL AND METHODS: This questionnaire survey study was sent to
laboratories participating in the Dutch external quality control program for
semen analysis (SKML) and consisted of 46 questions concerning laboratory
management, methods for semen analysis and IUI, and clinical results. The results
were analyzed using univariable and multivariable logistic regression models.
RESULTS: A total of 52 laboratories (out of 99) provided information on used
methodologies for SA or laboratory procedures of IUI and the organization of the
laboratory. A wide variability was confirmed in used methods for both SA and IUI.
Evaluation of pregnancy results obtained during 3 years (2013-2015) showed that
specific used laboratory methods have a significant effect on the probability of
becoming pregnant. DISCUSSION AND CONCLUSION: Important to remark is that in this
survey study cycle-specific data, including variables of the individual couples
(age, stimulation protocol, etc), were not included and may have effects on the
results. The reported results provide an overview of the current practice
performance; however, the organization of fertility laboratories is changing
rapidly. The use of standardized methods in IUI is important for optimizing the
performance of care and improving pregnancy results. The knowledge on used
procedures, however, is limited, and further research on factors involving SA and
the IUI procedure is necessary.
PMID- 29959834
TI - Terapixel hyperspectral whole-slide imaging via slit-array detection and
projection.
AB - Digital pathology via whole-slide imaging (WSI) systems has recently been
approved for the primary diagnostic use in the US. Acquiring whole-slide images
with spectral information at each pixel permits the use of multiplexed antibody
labeling and allow for the measurement of cellularly resolved chemical
information. Here, we report the development of a high-throughput terapixel
hyperspectral WSI system using prism-based slit-array dispersion. We demonstrate
a slit-array detection scheme for absorption-based measurements and a slit-array
projection scheme for fluorescence-based measurements. The spectral resolution
and spectral range in the reported schemes can be adjusted by changing the
orientation of the slit-array mask. We use our system to acquire 74 5-megapixel
brightfield images at different wavelengths in ~1 s, corresponding to a
throughput of 0.375 gigapixels / s. A terapixel whole-slide spatial-spectral
data cube can be obtained in ~45 min. The reported system is compatible with
existing WSI systems and can be developed as an add-on module for whole-slide
spectral imaging. It may find broad applications in high-throughput chemical
imaging with multiple antibody labeling. The use of slit array for structured
illumination may also provide insights for developing high-throughput
hyperspectral confocal imaging systems.
PMID- 29959835
TI - Feasibility study on mouse live imaging after spinal cord injury and poly(lactide
co-glycolide) bridge implantation.
AB - Spinal cord injury (SCI) causes permanent paralysis below the damaged area. SCI
is linked to neuronal death, demyelination, and limited ability of neuronal
fibers to regenerate. Regeneration capacity is limited by the presence of many
inhibitory factors in the spinal cord environment. The use of poly(lactide-co
glycolide) (PLG) bridges has demonstrated the ability to sustain long-term
regeneration after SCI in a cervical hemisection mouse model. Critically, imaging
of regenerating fibers and the myelination status of these neuronal filaments is
a severe limitation to progress in SCI research. We used a transgenic mouse model
that selectively expresses fluorescent reporters (eGFP) in the neuronal fibers of
the spinal cord. We implanted a PLG bridge at C5 vertebra after hemisection and
evaluated in live animals' neuronal fibers at the bridge interface and within the
bridge 8 weeks postimplant. These in vivo observations were correlated with in
situ evaluation 12 weeks postimplantation. We sectioned the spinal cords and
performed fluorescent bioimaging on the sections to observe neuronal fibers going
through the bridge. In parallel, to visualize myelination of regenerated axons,
we exploited the characteristics of the third-harmonic generation arising from
the myelin structure in these fixed sections.
PMID- 29959836
TI - Tackle the complexity. Pharmaceutical care to the chronic complex patient.
PMID- 29959837
TI - The impact of automation on the safety of drug dispensing in nursing homes.
AB - OBJECTIVE: To compare the frequency and seriousness of notified dispensing errors
in nursing homes when medication is dispensed manually versus automatically using
a specifically selected automatic dispensing system. METHOD: A pre-post
retrospective observational study in 7 nursing homes. We compare voluntarily
notified dispensing errors in a manually dispensed weekly system on the one hand
(year 2013), with an Automated Tablet Dispensing and Packaging System Xana4001U2
Tosho(r) for oral solid drugs used in combination with a manual system for other
drug forms (year 2015), on the other. We analyze patient function, cognition and
pharmacological data in two time periods. RESULTS: Residents' mean age (83.9 vs
83.6 years; p > 0.05) and physical functioning (Barthel index 41.8 vs 44.2; p >
0.05) were similar, but not cognitive functioning (MMSE 20.3 vs 21.7; p <
0.0,5). During the year previous to the automated dispensing, 408 errors were
detected with the manual system, whereas only 36 were detected in the following
yearwith the automated system. This represents a reduction of 91% in dispensing
errors. 43 errors reached the patient during the manually dispensing year, versus
6 during the automated year. And 5 errors versus 1 required monitoring.
CONCLUSIONS: The introduction of an automatic tablet dispensing and packaging
system has shown to be an important improvement in safety in the dispensing and
administration of solid drugs in nursing homes. The voluntary notification of
errors has permitted the comparison of safety during two time periods with
different dispensing systems.
PMID- 29959838
TI - Treatment adherence in patients older than 65 years who suffer early
readmissions.
AB - OBJECTIVE: Analyze the frequency of therapeutic noncompliance in patients who
suffer early readmissions, and identify the factors associated with it. METHOD:
Observational, descriptive study of three months duration (March - May 2014).
All patients older than 65 years who readmitted in the 3-30 days following the
last hospital discharge were included. We excluded programmed re-admissions and
readmissions in the Intensive Care Unit. The variables collected were: age, sex,
medical service, major diagnostic category, polypharmacy, number of days since
the last hospital discharge, presence of hypertension and/or diabetes. The
therapeutic compliance and the difficulty in the administration of medication
were evaluated by means of the Morisky-Green test and the Haynes-Sackett test
respectively. A descriptive analysis of the variables was carried out and they
were related to the therapeutic adherence. The variables with statistical
significance were included in a multivariate logistic regression model. RESULTS:
Fifty seven percent of the patients presented lack of adherence to
pharmacological treatment. Twenty three percent had difficulty administering the
medication. Eighty six percent had comorbidities (hypertension and/or diabetes)
and 79% had a caregiver. Eighty six percent of patients were polymedicated (>= 5
drugs). There is a relationship between lack of adherence and difficulty in the
administration of medications (p=0.021), polypharmacy (p=0.002), and the
presence of diabetes mellitus (p=0.018). CONCLUSIONS: Polymedication, the
presence of diabetes mellitus and the existence of difficulty in the
administration of medication are evidenced as prognostic factors of the lack of
adherence to treatment in patients older than 65 years.
PMID- 29959839
TI - Hazardous drugs levels in compounding area surfaces of Hospital Pharmacies
Services: multicentric study.
AB - OBJECTIVE: Hazardous drugs presence at Hospital Pharmacies has been demonstrated
in numerous studies. This study aims to analyze the presence and levels of
hazardous drugs at Spanish Hospital Pharmacies and the influence of different
aspects on them. METHOD: We developed a cross test at Hospital Pharmacies
hazardous drugs compounding surfaces of ten Spanish hospitals. An independent
laboratory determined cyclophosphamide, iphosphamide and 5-fluorouracile levels
in samples recovered. Annual number of hazardous drugs compounded, as well as
the number of preparations developed the testing day was registered. We also
registered cleaning and decontamination processes and the drug transfer device
used at each hospital. RESULTS: 204 samples were analyzed. Hazardous drugs
presence was confirmed in all participant hospitals. We observed a 49%, 23% and
10% of positive samples for cyclophosphamide, iphosphamide and 5-fluorouracile.
Median levels (first-third quartile) of cyclophosphamide, iphosphamide and 5
fluorouracile were 0.05 ng/cm2 (0.03-0.23), 0.03 ng/cm2 (0.03- 0.06) y 0.31
ng/cm2 (0.3- 0.59) respectively. CONCLUSIONS: Present study confirms hazardous
drugs presence at Spanish Hospital Pharmacies departments. We observed a
significant variability between participant hospitals, as well as between tested
locations. Samples with more positive results were cabine airfoils and floors in
front of them. The number of preparations had no influence on results observed.
Variability observed points outs the need to standardized compounding hazardous
drugs processes.
PMID- 29959840
TI - Approach to the development of a frailty index based on comprehensive geriatric
assessment in nursing home.
AB - OBJECTIVE: To carry out an approach for the development of a frailty index in
nursing homes and to analize its potential use in order to individualize the
pharmacological treatment. METHOD: The frailty index was constructed from the
information included in the comprehensive geriatric assessment established in
nursing homes. The index has been retrospectively applied to the patients of two
centers using the last comprehensive geriatric assessment of each one. RESULTS:
17 variables that included 27 deficits were selected and classified in 4
domains. 269 patients (mean age 82.9 +/- 8.8 years) were included in the
analysis. The frailty index indicated that 86% of patients should be considered
frail and 60% of these to moderate-advanced level. CONCLUSIONS: The frailty index
is simple and quick to apply. It seems to have discriminative capacity in terms
of quantifying the degree of frailty and it could be useful in prescribing the
most appropriate therapeutic aggressiveness to each patient.
PMID- 29959841
TI - Potential interactions in a cohort of elderly hiv-positive patients.
AB - OBJECTIVE: The increase of HIV-patients life expectancy leads to a new model of
patient with chronic diseases and polymedicated. For this reason we ought to
know in clinical practice the prevalence of polypharmacy and drug-drug
interactions between the antiretroviral drugs and comedication in our patients in
order to identify and prevent them. METHOD: A retrospective, descriptive study
carried out in > 50 years old patients on antiretroviral treatment. Results: We
included 242 patients of whom 148 (61%) were receiving concomitant treatment. 243
potential interactions were detected, where 197 are considered moderate and 46
severe, affecting 110 patients. 35 (76%) interactions were related to boosted
protease inhibitors. The main consequence of these interactions was the increase
in plasma concentrations of comedication (48%). Statins were the comedication
most involved in severe drug-druginteractions (24%), followed by inhaled
corticosteroids (15%). CONCLUSIONS: Polypharmacy was found in about half of our
study population and the prevalence of drug-drug interactions was high. Hospital
pharmacists may play a crucial role in their detection, management and early
communication.
PMID- 29959842
TI - A systematic review about prophylactic L-carnitine administration in parenteral
nutrition of extremely preterm infants.
AB - OBJECTIVE: Preterm infants with total parenteral nutrition are at particular risk
of developing carnitine deficiency with impaired tolerance of parenteral lipids.
The objective was to review the scientific literature on potencial benefits of
prophylactic L-carnitine administration in parenteral nutrition of preterm
newborns. METHODS: Selected scientific articles in MEDLINE/PubMed, Scopus, The
Cochrane Library, British Library EThOS and TESEO databases were assessed for
this systematic review. The terms used as descriptors were "Total Parenteral
Nutrition" and "Carnitine". Jadad scale was chosen to evaluate the quality of
them. RESULTS: 18 out of the 93 references retrieved were selected for reviewing
after applying the inclusion and exclusion criteria, 4 of them were discarded
for being considered of low quality. Almost all studies agreed on the analytical
variables measured (free carnitine and acylcarnitine, triglycerides, free fatty
acids and ketone bodies). Other clinical variables such as weight gain, apnea,
or lenght of stay at hospital were also considered. CONCLUSIONS: The present
results prove that routine supplementation in the parenteral nutrition of
preterm newborns may help to increase carnitine levels, but neither a relevant
improvement in the lipid profile, or an increase in weight gain, or a decrease
in morbimortality or reduction of hospital stay could be demonstrated. More
studies are needed in preterm infants to know whether routine supplementation of
L-carnitine in neonates requiring total parenteral nutrition for a long time
would provide any clinical benefit.
PMID- 29959843
TI - Life medicalization and the recent appearance of "pharmaceuticalization".
AB - Medicalization is a concern to which we have been paying attention intermittently
for the past half century. However, it is increasingly difficult to look away
from its multiple and ubiquitous manifestations, and therefore there is an
increasingly higher number of analysis and studies about them, from the most
varied perspectives, not only by healthcare literature, but also with the great
contribution by social sciences such as Anthropology or Sociology.Based on
previous publications, this article offers an updated review on life
medicalization in the European setting, highlighting particularly those
situations where a medication is the main vehicle for medicalization. This
demands a careful exploration of the "pharmaceuticalization" concept, which
appeared in the past decade, and which many of the research projects with these
characteristics intend to embrace.The decentralized nature of the decisions on
diagnosis and treatment requires an agreement of healthcare professionals on the
presumed benefits of certain therapeutic interventions as key factor to the
expansion of medicalization. Even so, there are multiple interactions and
synergies between incentives and economic interests in the medicalization
process, as well as bias in the generation of knowledge, the training for
professionals, their need to cope with patient expectations, progressively
overcoming their resolution capacities, and the mechanisms for structuring said
expectations. A better understanding of the dispositifs that promote
medicalization (the strategy without a strategist that becomes visible through
its cumulative outcome, but is less clearly seen by the different agents,
sometimes contradictory, working through it) is essential in order to limit its
most undesirable expansions.
PMID- 29959844
TI - Spanish Society of Hospital Pharmacy position paper on biosimilar medicines.
AB - Biological medicines nowadays have a great impact, as they offer treatment for
diverse diseases and suppose a high cost for health system. Biosimilar medicines
contain a version of an active substance already authorized as an original
biotechnological medicine, whose patent has expired, and they comply with the
guidelines published by the European Medicines Agency. These guidelines, where
biosimilarity criteria are established, guarantee comparability between
biosimilar product and reference one. Biosimilars' authorization is carried out
through a centralized procedure based on clinical, non-clinical and quality
studies. These studies allow the extrapolation of indications, frequently,
without carrying out additional analyses. In several European countries,
switching between original and biosimilar medicine is considered safe. In Spain,
Pharmacy and Therapeutic Committee of hospitals, as consensus bodies among health
professionals, are the most suitable bodies to establish the interchangeability
criteria in each center. Biosimilar drugs contribute to sustainability and to
improvement of the accessibility to medicines. Faced with this situation,
Spanish Society of Hospital Pharmacy considers interesting to express its
position about biosimilar medicines' strategies. Spanish Society of Hospital
Pharmacy, in September 2015, published an information note about biosimilar
medicines, in which its role as medicines similar in quality, safety and
efficacy to the originals, but at lower cost, was highlighted. Likewise, it was
stressed the role of hospital pharmacists within the Pharmacy and Therapeutic
Committee of hospitals, where their knowledge for the selection, evaluation and
use of medicines could be useful, in coordination and permanent collaboration
with other units or clinical services of hospitals.
PMID- 29959845
TI - [The role of the economic evaluation in the Pharmacoterapeutic Committees of the
two hospital of third level].
PMID- 29959846
TI - Computed Tomographic Studies of Noncalcified Nodules Related to Neuroendocrine
Lung Tumor Using 68Gallium-Tagged Somatostatin Variant for Improvement in
Diagnosis: A Non-Experimental, Non-Randomized, Cross-Sectional Study.
AB - BACKGROUND 18Fluoro-fluorodeoxyglucose (FDG)- based positron-emission computed
tomography (PET) has less specificity for noncalcified nodules (NNs).
Somatostatin receptors affect the expression of normal and malignant cells. The
purpose of the study was to compare the sensitivity, specificity, and accuracy of
68Gallium-tagged DOTA-octreotate (Ga-tDO) with that of FDG PET for diagnosis of
newly detected and/or untreated NNs in lung cancer patients. MATERIAL AND METHODS
A total of 45 patients with lung cancer were included in the cross-sectional
study and underwent Ga-tDO and FDG PET. We further confirmed observed outcomes by
testing immune histochemical staining for subtype 2A of somatostatin receptor in
a granuloma tissue array. The chi-square test was performed for sensitivity and
specificity of predictive values among the 3 diagnostic modalities. McNemar's
test was performed to compare accuracy between Ga-tDO and FDG PET. Results were
considered significant at 95% confidence level. RESULTS Ga-tDO had less
sensitivity (69% vs. 89%) but more specificity (91% vs. 78%) than FDG PET. Ga-tDO
and FDG PET were characterized as 36 and 6 and in 36 and 3 lesions as accurate
and inaccurate, respectively. There was an insignificant difference between Ga
tDO and FDG PET regarding diagnostic accuracy (p=0.7). Dosimetry results showed
that the lungs were one of the least critically affected organs. CONCLUSIONS Ga
tDO was more specific but less sensitive than FDG PET scanning and imaging.
PMID- 29959847
TI - ThedaCare Nutrition Risk Screen Improves the Identification of Non-Intensive Care
Unit Patients at Risk for Malnutrition Compared With the Nutrition Risk Screen
2002.
AB - BACKGROUND: Identification of patients at risk for malnutrition is important for
timely nutrition intervention to reduce morbidity and mortality. OBJECTIVE: The
objective of this study was to compare the sensitivity and specificity of the
Nutrition Risk Screen (NRS) 2002 and the ThedaCare NRS to identify patients at
risk for malnutrition. METHODS: The NRS 2002 and ThedaCare NRS were administered
to 594 patients, aged 63 +/- 16 years (mean +/- SD), in the non-intensive care
unit hospital setting. Risk for malnutrition and malnutrition diagnosis were
confirmed with the 6 malnutrition clinical characteristics defined by the Academy
of Nutrition and Dietetics and the American Society for Parenteral and Enteral
Nutrition and using the nutrition assessment that included the Nutrition Focused
Physical Exam. Sensitivity, specificity, and kappa coefficient were calculated.
RESULTS: When compared with the NRS 2002, the ThedaCare NRS had higher
sensitivity (98.8% vs 63.5%), indicating improved identification of patients at
risk for malnutrition, but lower specificity (74.0% vs 93.4%), indicating that
more patients at low risk for malnutrition were misclassified. ThedaCare NRS
missed fewer patients at risk for malnutrition when compared with the NRS 2002.
ThedaCare NRS had a higher kappa coefficient when compared with the NRS 2002,
indicating better agreement of results regardless of who administered the screen.
The ThedaCare NRS required less time to complete when compared with the NRS 2002
(mean +/- SE: ThedaCare, 17 +/- 1 seconds; NRS 2002, 9 +/- 1 minutes; P < .0001).
CONCLUSION: The ThedaCare NRS improves the identification of patients at risk for
malnutrition in the non-intensive care unit hospital setting. This trial was
registered at www.clinicaltrials.gov as NCT02585245.
PMID- 29959848
TI - Comparison of Two Methods for Estimating the Tip Position of a Nasogastric
Feeding Tube: A Randomized Controlled Trial.
AB - BACKGROUND: Several studies have shown that the nose-earlobe-xiphoid distance
(NEX) is inadequate to estimate the insertion length of nasogastric tubes. An
alternative approach tested in these studies, which leads to > 90% well-placed
nasogastric tubes, used a corrected calculation of the NEX: (NEX * 0.38696) +
30.37. The primary aim of this study was to determine whether using the corrected
NEX was more successful than the NEX in determining the insertion length. The
secondary aim was to investigate the likelihood to successfully obtain gastric
aspirate. METHODS: Adult patients in a general hospital (N = 215) needing a
nasogastric tube were randomized to the control (NEX) or intervention group
(corrected NEX). Tip positioning was verified using X-ray. Correct tip
positioning was defined as between 3 and 10 cm under the lower esophageal
sphincter (LES). RESULTS: In >20% of all patients, both methods underestimated
the required tube length for correct positioning. The NEX showed an
overestimation (17.2%) of the insertion length (>10 cm under the LES) compared
with the corrected NEX (4.8%). There was no difference (P = 0.938) between the 2
groups in obtaining gastric aspirate (55.6% vs 56%). However, correct tip
positioning resulted in a fourfold increase of obtaining gastric aspirate.
CONCLUSIONS: Both methods resulted in a high risk of incorrectly placed tubes due
to malposition of the tip near the LES or distal esophagus. This may increase the
risk of reflux and pulmonary aspiration. Based on these results, the development
of more reliable methods requires consideration.
PMID- 29959849
TI - A Light-Up Probe with Aggregation-Induced Emission for Real-Time Bio-orthogonal
Tumor Labeling and Image-Guided Photodynamic Therapy.
AB - Bio-orthogonal tumor labeling is more effective in delivering imaging agents or
drugs to a tumor site than active targeting strategy owing to covalent ligation.
However, to date, tumor-specific imaging through bio-orthogonal labeling largely
relies on body clearance to differentiate target from the intrinsic probe signal
owing to the lack of light-up probes for in vivo bio-orthogonal labeling. Now the
first light-up probe based on a fluorogen with aggregation-induced emission for
in vivo bio-orthogonal fluorescence turn-on tumor labeling is presented. The
probe has low background fluorescence in aqueous media, showing negligible non
specific interaction with normal tissues. Once it reacts with azide groups
introduced to tumor cells through metabolic engineering, the probe fluorescence
is lightened up very quickly, enabling rapid tumor-specific imaging. The
photosensitizing ability was also used to realize effective image-guided
photodynamic tumor therapy.
PMID- 29959850
TI - JPEN Journal Club 36. Quasirandomization.
PMID- 29959851
TI - Greater Nutrient Intake Is Associated With Lower Mortality in Western and Eastern
Critically Ill Patients With Low BMI: A Multicenter, Multinational Observational
Study.
AB - BACKGROUND: Little is known about the impact of feeding adequacy by NUTrition
Risk in the Critically Ill (NUTRIC) groups in critically ill patients with body
mass index (BMI) <20. Our purpose was to assess whether adequacy of
protein/energy intake impacts mortality in patients with BMI <20 in
Western/Eastern intensive care units (ICUs) and high/low NUTRIC groups. METHODS:
Data from the International Nutrition Survey 2013-2014 were dichotomized into
Western/Eastern ICU settings; BMI <20 or >=20; and high (>=5)/low (<5) NUTRIC
groups. Association of BMI <20 with 60-day mortality was compared in unadjusted
and adjusted (Western/Eastern, age, medical/surgical admission, high/low NUTRIC
group) logistic regression models. The impact of adequacy of protein/energy on 60
day mortality relationship was tested using general estimating equations in
high/low NUTRIC groups, in unadjusted and adjusted models. RESULTS: Western (n =
4274) patients had higher mean BMI (27.9 +/- 7.7 versus (vs) 23.4 +/- 4.9, P <
0.0001) than Eastern (n = 1375), respectively. BMI <20 was associated with
greater mortality (adjusted odds ratio [OR] 1.30, 95% confidence interval [CI]
1.07-1.57), with no interaction between BMI group and Western/Eastern ICU site.
Among patients with BMI <20 and high NUTRIC score, 10% greater protein and energy
adequacy was associated with 5.7% and 5.5% reduction in 60-day mortality,
respectively. Results were not significantly different between Western and
Eastern ICUs. CONCLUSIONS: The benefit of greater protein/energy intake in high
NUTRIC patients was observed regardless of geographic origin or low BMI,
suggesting a consistent response to nutrition support in this group. Clinical
guidelines and research projects focused on improving care in high-risk
critically ill patients can be applied across geographic boundaries.
PMID- 29959852
TI - Enteral Protein Supplementation in Critically Ill Children: A Randomized
Controlled Pilot and Feasibility Study.
AB - BACKGROUND: Loss of muscle mass in critically ill children can negatively impact
outcomes. The aims of this study were to conduct a pilot randomized control trial
(RCT) to examine the difference in protein delivery and nitrogen balance in
critically ill children with enteral protein supplementation vs controls. We also
aimed to assess the feasibility, safety, and tolerance of the pilot trial.
METHODS: This is a 3-arm RCT in critically ill children eligible for enteral
nutrition (EN) therapy. Patients were randomized to 1 of the 3 groups: (1)
control (routine EN), (2) polymeric protein module added to EN to reach protein
goal by day 4, or (3) oligomeric protein supplementation. Demographics, clinical
characteristics, nutrition status, and daily nutrition intake variables were
recorded. Protein delivery, nitrogen balance, feasibility variables, and rate of
adverse events were the outcomes. RESULTS: After screening 286 consecutive
patients admitted to the pediatric intensive care unit over 11 months, we
enrolled and randomized 25 patients. Twenty-two patients (88% of the enrolled)
completed the study procedures. Significantly higher protein prescription and
actual protein intake within the first 5 days was achieved in the intervention
groups, compared with the control group. Nitrogen balance was obtained in 15
patients. There was no significant difference between the groups for the rate of
adverse effects and clinical outcomes. CONCLUSION: In our pilot trial, protein
supplementation was safe and well tolerated. Our preliminary results suggest that
a larger RCT is potentially feasible, with some modifications of the entry
criteria. Trial enrollment was low, likely due to restrictive entry criteria.
PMID- 29959853
TI - Has the role of skin ultrasound for Systemic sclerosis been defined?
AB - Attempting to implement the constructive comments reported in their Letter by A.
Lescoat and Colleagues, we are convinced that the application of ultrasound (US)
has the potential to become a reliable and valuable tool to evaluate various body
sites, including the musculoskeletal and vascular system, lungs and skin.
Therefore, contributing to the clinical assessment of complex diseases, such as
systemic sclerosis (SSc) (1). This article is protected by copyright. All rights
reserved.
PMID- 29959854
TI - Imaging in Systemic Sclerosis: make "US" great again?
AB - In this issue of Arthritis Care & Research, T. Santiago and colleagues [1] have
conducted an informative systematic literature review on the relevance of
ultrasound (US) for the assessment of skin involvement in systemic sclerosis
(SSc). In this Original Article, the authors highlight the heterogeneous results
concerning the reliability of US in studies published to date, but also
underscore very promising data from recently published articles [2]. Moreover,
this work raises the issue considering US evaluation as an interesting
alternative to mRSS for skin assessment in SSc. Therefore, beyond imaging
considerations, this article questions the place of US evaluation in the global
management of SSc. This topic is still a controversial matter as new assessment
technics are emerging for microvascular, macrovascular and musculoskeletal
evaluations in SSc This article is protected by copyright. All rights reserved.
PMID- 29959855
TI - Morphological Growth and Theoretical Understanding of Gold and Other Noble Metal
Nanoplates.
AB - For the last decades, the chemical reduction of Au3+ to Au0 has been widely
employed to produce various gold nanostructures. In comparison with the fast
reduction, the slow reduction is systematically investigated in this research to
provide more insights to reveal intermediary process and further disclose the
underlying mechanism for growing gold nanostructures by using a series of simple
ligands with aldehyde groups as weak reducing agents. The different binding
energies of ligands to Aun+ (n=3, 1 and 0) exhibit variable binding affinities in
starting, intermediate, and final gold species. For example, formic acid has much
stronger binding affinity to Au+ than Au3+ , and thus Au+ intermediate is able to
be stabilized/captured during slow reduction of Au3+ . Upon the
disproportionation of Au+ to Au0 and Au3+ , formic acid has much stronger binding
affinity to the newly formed Au0 than other ligands for the controlled formation
of gold nanostructures. Meanwhile, the adsorption of ligands causes substantially
decreased surface energies on different gold planes. There are much higher
energies on {110} planes compared to the other two {111} and {100} planes with
certain ratios in these energies, leading to morphological growth of gold
nanosheets. In this paper, we experimentally demonstrate anisotropic growth of
gold nanosheets by using various ligands with weak reducing and appropriate
coordination capabilities, and further provide insights to understand their
morphological growth mechanism behind. This synthetic strategy is successfully
extended to prepare silver, palladium, and platinum nanoplates.
PMID- 29959856
TI - Transition Metal Carbide Complex Architectures for Energy-Related Applications.
AB - Transition metal carbides (TMCs), as a family of special interstitial alloys,
exhibit novel intrinsic characteristics such as high melting point, high
electronic conductivity, excellent mechanical and chemical stability, and good
corrosion resistance, and hence have attracted ever-growing attention as
promising electrode materials for energy-related applications. In this regard, we
give a comprehensive overview of the structural design of transition metal
carbide complex architectures and their structure advantages for energy-related
applications. After a brief classification, we summarize in detail recent
progress in controllable design and synthesis of TMCs with complex nanostructures
(e.g., zero-, one-, two-, and three-dimensional, and self-supported electrodes)
for electrochemical energy storage and conversion applications including metal
ion batteries, supercapacitors, rechargeable metal-air batteries, fuel cells, and
water splitting. Finally, we end this review with some potential challenges and
research prospects of TMCs as electrode materials for energy-related
applications.
PMID- 29959857
TI - Sp1 mediates phorbol ester (PMA)-induced expression of membrane-bound guanylyl
cyclase GC-A in human monocytic THP-1 cells.
AB - Cyclic guanosine monophosphate (cGMP) is synthesized by two types of enzymes:
particulate (membrane-bound) guanylyl cyclases (pGCs) and soluble (cytosolic)
guanylyl cyclases (sGCs). sGCs are primarily activated by binding of nitric oxide
to their prosthetic heme group while pGCs are activated by binding of peptide
ligands to their extracellular domains. One of them, pGC type A (GC-A) is
activated by atrial and brain natriuretic peptides (ANP and BNP, respectively).
Human monocytes isolated from peripheral blood mononuclear cells have been found
to display sGC expression without concomitant expression of GC-A. However, GC-A
activity appears in monocytes under certain conditions but a molecular mechanism
of GC-A expression is still poorly understood. In this report we show that
phorbol ester (PMA) induces transcription of a gene encoding GC-A in human
monocytic THP-1 cells. Moreover, we find that PMA-treated THP-1 cells raise cGMP
content following treatment with ANP. Studies using pharmacological inhibitors of
protein kinases suggest involvement of protein kinase C (PKC), mitogen
extracellular kinases (MEK1/2), and extracellular signal-regulated kinases
(ERK1/2) in PMA-induced expression of the GC-A encoding gene in THP-1 cells.
Finally, we show that PMA stimulates binding of Sp1 transcription factor to GC
rich DNA sequences and mithramycin A (a selective Sp1 inhibitor) inhibits
expression of the GC-A mRNA in PMA-treated THP-1 cells. Taken together, our
findings suggest that the PMA-stimulated PKC and MEK/ERK signaling pathways
induce Sp1-mediated transcription of the GC-A encoding gene in human monocytic
THP-1 cells.
PMID- 29959858
TI - Machado-Joseph disease/spinocerebellar ataxia type 3: lessons from disease
pathogenesis and clues into therapy.
AB - Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3),
is an incurable disorder, widely regarded as the most common form of
spinocerebellar ataxia in the world. MJD/SCA3 arises from mutation of the ATXN3
gene, but this simple monogenic cause contrasts with the complexity of the
pathogenic mechanisms that are currently admitted to underlie neuronal
dysfunction and death. The aberrantly expanded protein product - ataxin-3 - is
known to aggregate and generate toxic species that disrupt several cell systems,
including autophagy, proteostasis, transcription, mitochondrial function and
signalling. Over the years, research into putative therapeutic approaches has
often been devoted to the development of strategies that counteract disease at
different stages of cellular pathogenesis. Silencing the pathogenic protein,
blocking aggregation, inhibiting toxic proteolytic processing and counteracting
dysfunctions of the cellular systems affected have yielded promising ameliorating
results in studies with cellular and animal models. The current review analyses
the available studies dedicated to the investigation of MJD/SCA3 pathogenesis and
the exploration of possible therapeutic strategies, focusing primarily on gene
therapy and pharmacological approaches rooted on the molecular and cellular
mechanisms of disease.
PMID- 29959859
TI - Lignocellulosic biomass to biofuels and biochemicals: A comprehensive review with
a focus on ethanol organosolv pretreatment technology.
AB - Lignocellulosic biomass is one of the potential feedstocks to produce second
generation cellulosic ethanol and biochemicals. To enhance the enzymatic
digestibility of lignocellulosic biomass for efficient enzymatic
saccharification, a variety of pretreatment methods have been studied. Among
these, organosolv pretreatment using ethanol is a promising pretreatment method
owing to its inherent advantages, such as low solvent cost, lack of toxicity, the
ability to retain most cellulose fraction in substrates for enzymatic hydrolysis,
coproduction of high-purity lignin and hemicellulosic sugars, easy solvent
recovery, and reuse. In this review, the research progress regarding different
types of ethanol organosolv pretreatment processes has been summarized in terms
of methods, substrate properties, reaction mechanisms, delignification kinetic as
well as the impact of pretreatment methods on the enzymatic digestibility.
Attempts are also made to provide insights into the complete utilization of
lignocellulosic biomass to achieve high potential revenues. Though some ethanol
organosolv processes have been studied or are being developed towards
commercialization, ethanol organosolv pretreatment is still facing some
challenges. Finally, the direction for future work is given to develop a proper
ethanol organosolv pretreatment for commercialization.
PMID- 29959861
TI - Sphingolipids and neuronal degeneration in lysosomal storage disorders.
AB - Ceramide, sphingomyelin, and glycosphingolipids (both neutral and acidic) are
characterized by the presence in the lipid moiety of an aliphatic base known as
sphingosine. Altogether, they are called sphingolipids and are particularly
abundant in neuronal plasma membranes, where, via interactions with the other
membrane lipids and membrane proteins, they play a specific role in modulating
the cell signaling processes. The metabolic pathways determining the plasma
membrane sphingolipid composition are thus the key point for functional changes
of the cell properties. Unnatural changes of the neuronal properties are observed
in sphingolipidoses, lysosomal storage diseases occurring when a lysosomal
sphingolipid hydrolase is not working, leading to the accumulation of the
substrate and to its distribution to all the cell membranes interacting with
lysosomes. Moreover, secondary accumulation of sphingolipids is a common trait of
other lysosomal storage diseases. This article is part of the Special Issue
"Lysosomal Storage Disorders".
PMID- 29959860
TI - A motor neuron strategy to save time and energy in neurodegeneration: adaptive
protein stoichiometry.
AB - Neurofilament proteins (Nf) are a biomarker of disease progression in amyotrophic
lateral sclerosis (ALS). This study investigated whether there are major
differences in expression from in vivo measurements of neurofilament isoforms,
from the light chain, NfL (68 kDa), compared with larger proteins, the medium
chain (NfM, 150 kDa) and the heavy (NfH, 200-210 kDa) chains in ALS patients and
healthy controls. New immunological methods were combined with Nf subunit
stoichiometry calculations and Monte Carlo simulations of a coarse-grained Nf
brush model. Based on a physiological Nf subunit stoichiometry of 7 : 3 : 2
(NfL:NfM:NfH), we found an 'adaptive' Nf subunit stoichiometry of 24 : 2.4 : 1.6
in ALS. Adaptive Nf stoichiometry preserved NfL gyration radius in the Nf brush
model. The energy and time requirements for Nf translation were 56 +/- 27k ATP
(5.6 h) in control subjects compared to 123 +/- 102k (12.3 h) in ALS with
'adaptive' (24:2.4:1.6) Nf stoichiometry (not significant) and increased
significantly to 355 +/- 330k (35.5 h) with 'luxury' (7:3:2) Nf subunit
stoichiometry (p < 0.0001 for each comparison). Longitudinal disease progression
related energy consumption was highest with a 'luxury' (7:3:2) Nf stoichiometry.
Therefore, an energy and time-saving option for motor neurons is to shift protein
expression from larger to smaller (cheaper) subunits, at little or no costs on a
protein structural level, to compensate for increased energy demands.
PMID- 29959862
TI - Outline-etching image segmentation reveals enhanced cell chirality through
intercellular alignment.
AB - Cells cultured on micropatterns exhibit a chiral orientation, which may underlie
the development of left-right asymmetry in tissue microarchitectures. To
investigate this phenomenon, fluorescence staining of nuclei has been used to
reveal such orientation. However, for images with high cell density, analysis is
difficult because of the overlapping nuclei. Here, we report an image processing
method that can acquire cell orientations within dense cell populations. After
initial separation based on Boolean addition of binarized images using global and
adaptive thresholds, the overlapping nucleus contours in the binarized images
were segmented by iteratively etching the outlines of nuclei, which allowed the
orientations of each cell to be extracted from densely packed cell clusters. In
applying this technique to cultured C2C12 myoblasts in micropatterned stripes on
different substrates, we found an enhanced chiral orientation on glass substrate.
More important, this enhanced chirality was consistently observed with increased
intercellular alignment and independent of cell-cell distance or cell density,
suggesting that intercellular alignment plays a role in determining the chiral
orientation. By segmenting single cells with intact orientation, this technique
offers an automated method for quantitative analysis with improved accuracy,
providing an essential tool for studying left-right asymmetry and other
morphogenic dynamics in tissue formation.
PMID- 29959863
TI - Scale-up of the ex vivo expansion of encapsulated primary human T lymphocytes.
AB - A number of evolving medical therapies call for the controlled expansion of
primary human T lymphocytes. After encapsulation in sodium cellulose sulfate
poly(diallyldimethyl) ammonium chloride polyelectrolyte capsules, T lymphocytes
can be expanded without persisting activation. Here, the challenge of scaling up
this process is addressed. Encapsulated T lymphocytes were cultured in spinner
flasks as well as in several types of the bioreactor, including fixed and
fluidized beds, a waved cell bag, and a standard stirred tank reactor (STR; 1-L
scale). Two proprietary T lymphocyte culture media as well as a standard RPMI
based medium were used. As before, encapsulation coincided with the presence of
only a low fraction of activated T lymphocytes (peripheral blood T cells) in the
total population. Unexpectedly, growth rates were lower in well-mixed reactors
than those in cultivations under static conditions, that is, in T-flasks.
Switching the STR to low oxygen conditions (40% air saturation) improved the
growth rates to the level of the static cultures and thus forms the potential
basis for efficient scale-up of T lymphocyte expansion.
PMID- 29959864
TI - Nasal high-flow therapy decreased electrical activity of the diaphragm in preterm
infants during the weaning phase.
AB - AIM: We evaluated whether nasal high-flow therapy was better than no respiratory
support during the weaning phase in preterm infants. METHODS: The study was
conducted in the neonatal intensive care unit of the Turku University Hospital
between September 2014 and August 2015. Preterm infants who were alternating
between nasal high-flow therapy and unassisted breathing were enrolled.
Electrical activity of the diaphragm (EAdi) was recorded and compared during
three-hour time periods for each option. RESULTS: We studied eight infants at a
median gestational age of 31 weeks. The EAdi peak was lower during nasal high
flow therapy when compared to no respiratory support (6.1 MUV vs 7.1 MUV, p =
0.02), but the EAdi minimum was similar with and without respiratory support.
Neural respiratory rate (62 vs 68 per minute, p = 0.02) and the frequency of
sighs (27.8 vs 37.9 per hour, p = 0.03) were lower during nasal high-flow therapy
than no respiratory support. CONCLUSION: Nasal high-flow therapy reduced
diaphragm activation in our cohort when compared to no respiratory support, as
indicated by the lower Edi peak. An increase in the respiratory rate and the sigh
frequency without respiratory support also suggests that nasal high-flow therapy
provided support during the weaning phase.
PMID- 29959865
TI - Design and modularized optimization of one-step production of N-acetylneuraminic
acid from chitin in Serratia marcescens.
AB - Chitin is an abundant, biorenewable, nitrogen-rich biomass feedstock that can be
potentially developed for biochemical production; however, efficient bioprocesses
have yet to be established. Here, we demonstrate an engineered bioprocess to
produce N-acetylneuraminic acid (Neu5Ac) directly from chitin using the
chitinolytic bacterium, Serratia marcescens by selecting and characterizing
promoters, characterization of heterologous enzyme activity, and optimization of
pathway fluxes. By generating RNASeq data for S. marcescens growth in different
carbon-limited conditions (glucose, N-acetylglucosamine, and glycerol), 12
promoters with varying strength were identified and characterized to implement
for transcriptional control. Neu5Ac production was initially engineered into S.
marcescens through heterologous expression of N-acetylglucosamine 2-epimerase
(slr1975) and N-acetylneuraminic acid aldolase (nanA). The activity of both genes
was characterized in vitro for kinetics and in vivo expression using promoters
identified in this study. Optimization of Neu5Ac production was accomplished by
balancing pathways fluxes through promoter swapping and replacing the reversible
nanA with the irreversible gene neuB. The optimized recombinant strain P T5
slr1975-P rplJ -neuB was able to produce 0.48 g/L Neu5Ac from 20 g/L N
acetylglucosamine, and 0.30 g/L Neu5Ac from 5 g/L crystal chitin. These results
represent the first demonstration of direct conversion of crystal chitin to N
acetylneuraminic acid.
PMID- 29959866
TI - Hepatitis C virus incidence in HIV-infected and in preexposure prophylaxis (PrEP)
using men having sex with men.
AB - BACKGROUND & AIMS: HCV incidence still appears on the rise in HIV-infected MSM in
France. We assessed the incidence of HCV infection in HIV-positive and in
preexposure prophylaxis (PrEP)-using MSM. METHODS: HIV-infected, HCV-negative MSM
with serological follow-up in 2016 and HIV-negative, HCV-negative PrEP-using MSM
enrolled from January 2016 to May 2017 in the French Dat'AIDS cohort were
analyzed to assess the incidence of a primary HCV infection. The incidence of HCV
reinfection was also determined in patients having cured a previous infection.
RESULTS: Among 10,049 HIV-infected MSM followed in 2016, 681 patients were
already HCV-infected when entering the study (prevalence 6.8%). Serological
follow-up was available in 2016 for 4,151 HCV-negative patients. Virological
follow-up was available for 478 patients who had cured a previous infection.
Fifty-seven HCV infections occurred in 2016 (42 primary infections, 15
reinfections). Incidence of primary HCV infection, reinfection and overall HCV
infection was respectively 1.0, 3.1 and 1.2/100 person-years (PY). From January
2016 to May 2017, 930 HIV-negative subjects were enrolled for PrEP. Seventeen
patients were already HCV-infected (prevalence 1.8%). Twelve HCV infections
occurred during follow-up (10 primary infections, 2 reinfections) giving an
incidence of primary infection of 1.0/100 PY and an overall incidence of 1.2/100
PY. CONCLUSIONS: The overall incidence of HCV infection and of a primary HCV
infection in HIV-positive and in PrEP-using MSM appeared similar in France in
2016-early 2017. HIV-positive and PrEP-using MSM probably share similar at-risk
practices and both should be targeted for preventative interventions. This
article is protected by copyright. All rights reserved.
PMID- 29959867
TI - Hepatocyte-like cells generated by direct reprogramming from murine somatic cells
can repopulate decellularized livers.
AB - Direct reprogramming represents an easy technique to generate induced hepatocytes
(iHeps) from somatic cells. However, current protocols are accompanied by several
drawbacks as iHeps are heterogenous and lack fully mature phenotypes of primary
hepatocytes. Here, we established a polycistronic expression system to induce the
direct reprogramming of mouse embryonic fibroblasts towards hepatocytes. The
resulting iHeps are homogenous and display key properties of primary hepatocytes,
such as expression of hepatocyte markers, albumin secretion, and presence of
liver transaminases. iHeps also possess the capacity to repopulate decellularized
liver tissue and exhibit enhanced hepatic maturation. As such, we present a novel
strategy to generate homogenous and functional iHeps for applications in tissue
engineering and cell therapy.
PMID- 29959868
TI - How to engineer glucose oxidase for mediated electron transfer.
AB - Glucose oxidase (GOx) is of high industrial interest for glucose sensing because
of its high beta-d-glucose specificity. The efficient and specific
electrochemical communication between the redox center and electrodes is crucial
to ensure accurate glucose determination. The efficiency of the electron transfer
rates (ETR) with GOx, together with quinone diamine based mediators, is low and
differs even among mediator derivatives. To design optimized enzyme-mediator
couples and to describe a mediator binding model, a joint experimental and
computational study was performed based on an oxygen-independent GOx variant V7
and two quinone diimine based electron mediators (QDM-1 and QDM-2), which differ
in polarity and size, and ferrocenemethanol (FM). A site saturation library at
position 414 was screened with all three mediators and yielded four beneficial
substitutions Tyr, Met, Leu, and Val. The variants showed increased mediator
activity for the more polar QDM-2 with a simultaneously decreased activity for
the less polar and smaller QDM-1 and for FM. The variant GOx V7-I414Y exhibited
the biggest change for the quinone diimine derivatives compared with V7 (QDM-1:
55.9 U/mg V7, 33.2 U/mg V7-I414Y; QDM-2: 2.7 U/mg V7, 12.9 U/mg V7-I414Y).
Theoretical ETR calculated based on the Marcus theory were in good agreement with
the experimental results. Molecular docking studies revealed a preferable binding
of the two QD mediators directly in the active site, 3.5 A away from the N5 atom
of the flavin adenine dinucleotide (FAD) and in direct vicinity to position 414.
In summary, position 414 in the active site was identified to modulate the
electron shuttling from the FAD of the GOx to small water-soluble mediators
dependent on the polarity and size of residue 414 and on the polarity and size of
the mediator. The presented mediator binding model offers a promising possibility
for the design of optimized enzyme-mediator couples.
PMID- 29959869
TI - Changes in autonomic regulation due to Kangaroo care remain unaffected by using a
swaddling device.
AB - AIM: To investigate the effects of a swaddling device known as the Hugsy (Hugsy,
Eindhoven, the Netherlands) towards improving autonomic regulation. This device
can be used both in the incubator and during Kangaroo care to absorb parental
scent and warmth. After Kangaroo care, these stimuli can continue to be
experienced by infants, while in the incubator. Additionally, a pre-recorded
heartbeat sound can be played. METHOD: Autonomic regulation was compared in
preterm infants before, during and after Kangaroo care with and without the use
of a swaddling device in a within-subject study carried out in a level III
neonatal intensive care unit. Descriptive statistics and effect sizes were
calculated corresponding to changes in heart rate, respiratory rate, oxygen
saturation, temperature and heart rate variability on intervention versus control
days. RESULTS: In this study of 20 infants with a median (interquartile range)
gestational age of 28.4 (27-29.9) weeks, Kangaroo care was associated with a
decrease in heart rate, respiratory rate and heart rate variability on both
intervention and control days. There were no differences between intervention and
control days. CONCLUSION: The use of an alternative swaddling device aimed at
facilitating Kangaroo care did not enhance autonomic regulation, as measured by
vital signs and heart rate variability.
PMID- 29959870
TI - C.B-17 SCID mice develop epicardial calcinosis with unaltered cardiac function.
AB - Inbred mouse strains are the most widely used mammalian model organism in
biomedical research owing to ease of genetic manipulation and short lifespan;
however, each inbred strain possesses a unique repertoire of deleterious
homozygous alleles that can make a specific strain more susceptible to a
particular disease. In the current study, we report dystrophic cardiac calcinosis
(DCC) in C.B-17 SCID male mice at 10 weeks of age with no significant change in
cardiac function. Acquisition of DCC was characterized by myocardial injury,
fibrosis, calcification, and necrosis of the tissue. At 10 weeks of age, 38% of
the C.B-17 SCID mice from two different commercial colonies exhibited significant
calcinosis on the ventricular epicardium, predominantly on the right ventricle.
The frequency of calcinosis was more than 50% for mice obtained from Taconic's
Cambridge City colony and 25% for mice obtained from Taconic's German Town
colony. Interestingly, the DCC phenotype did not affect cardiac function at 10
weeks of age. No differences in echocardiography or electrocardiography were
observed between the calcinotic and non-calcinotic mice from either colony. Our
findings suggest that C.B-17 SCID mice exhibit DCC as early as 10 weeks of age
with no significant impact on cardiac function. This strain of mice should be
cautiously considered for the study of cardiac physiology.
PMID- 29959871
TI - Interventions for treating acute high altitude illness.
AB - BACKGROUND: Acute high altitude illness is defined as a group of cerebral and
pulmonary syndromes that can occur during travel to high altitudes. It is more
common above 2500 metres, but can be seen at lower elevations, especially in
susceptible people. Acute high altitude illness includes a wide spectrum of
syndromes defined under the terms 'acute mountain sickness' (AMS), 'high altitude
cerebral oedema' and 'high altitude pulmonary oedema'. There are several
interventions available to treat this condition, both pharmacological and non
pharmacological; however, there is a great uncertainty regarding their benefits
and harms. OBJECTIVES: To assess the clinical effectiveness, and safety of
interventions (non-pharmacological and pharmacological), as monotherapy or in any
combination, for treating acute high altitude illness. SEARCH METHODS: We
searched CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science, CINAHL, Wanfang
database and the World Health Organization International Clinical Trials Registry
Platform for ongoing studies on 10 August 2017. We did not apply any language
restriction. SELECTION CRITERIA: We included randomized controlled trials
evaluating the effects of pharmacological and non-pharmacological interventions
for individuals suffering from acute high altitude illness: acute mountain
sickness, high altitude pulmonary oedema or high altitude cerebral oedema. DATA
COLLECTION AND ANALYSIS: Two review authors independently assessed the
eligibility of study reports, the risk of bias for each and performed the data
extraction. We resolved disagreements through discussion with a third author. We
assessed the quality of evidence with GRADE. MAIN RESULTS: We included 13 studies
enrolling a total of 468 participants. We identified two ongoing studies. All
studies included adults, and two studies included both teenagers and adults. The
13 studies took place in high altitude areas, mostly in the European Alps. Twelve
studies included participants with acute mountain sickness, and one study
included participants with high altitude pulmonary oedema. Follow-up was usually
less than one day. We downgraded the quality of the evidence in most cases due to
risk of bias and imprecision. We report results for the main comparisons as
follows.Non-pharmacological interventions (3 studies, 124 participants)All-cause
mortality and complete relief of AMS symptoms were not reported in the three
included trials. One study in 64 participants found that a simulated descent of
193 millibars versus 20 millibars may reduce the average of symptoms to 2.5 vs
3.1 units after 12 hours of treatment (clinical score ranged from 0 to 11 -
worse; reduction of 0.6 points on average with the intervention; low quality of
evidence). In addition, no complications were found with use of hyperbaric
chambers versus supplementary oxygen (one study; 29 participants; low-quality
evidence).Pharmacological interventions (11 trials, 375 participants)All-cause
mortality was not reported in the 11 included trials. One trial found a greater
proportion of participants with complete relief of AMS symptoms after 12 and 16
hours when dexamethasone was administered in comparison with placebo (47.1%
versus 0%, respectively; one study; 35 participants; low quality of evidence).
Likewise, when acetazolamide was compared with placebo, the effects on symptom
severity was uncertain (standardized mean difference (SMD) -1.15, 95% CI -2.56 to
0.27; 2 studies, 25 participants; low-quality evidence). One trial of
dexamethasone in comparison with placebo in 35 participants found a reduction in
symptom severity (difference on change in the AMS score: 3.7 units reported by
authors; moderate quality of evidence). The effects from two additional trials
comparing gabapentin with placebo and magnesium with placebo on symptom severity
at the end of treatment were uncertain. For gabapentin versus placebo: mean
visual analogue scale (VAS) score of 2.92 versus 4.75, respectively; 24
participants; low quality of evidence. For magnesium versus placebo: mean scores
of 9 and 10.3 units, respectively; 25 participants; low quality of evidence). The
trials did not find adverse events from either treatment (low quality of
evidence). One trial comparing magnesium sulphate versus placebo found that
flushing was a frequent event in the magnesium sulphate arm (percentage of
flushing: 75% versus 7.7%, respectively; one study; 25 participants; low quality
of evidence). AUTHORS' CONCLUSIONS: There is limited available evidence to
determine the effects of non-pharmacological and pharmacological interventions in
treating acute high altitude illness. Low-quality evidence suggests that
dexamethasone and acetazolamide might reduce AMS score compared to placebo.
However, the clinical benefits and harms related to these potential interventions
remain unclear. Overall, the evidence is of limited practical significance in the
clinical field. High-quality research in this field is needed, since most trials
were poorly conducted and reported.
PMID- 29959872
TI - Flavin-Containing Monooxygenase 3 Polymorphic Variants Significantly Affect
Clearance of Tamoxifen and Clomiphene.
AB - Human flavin-containing monooxygenase 3 (hFMO3) is a drug-metabolising enzyme
that oxygenates many drugs and xenobiotics in the liver. This enzyme is also
known to exhibit single nucleotide polymorphisms (SNPs) that can alter the rates
of monooxygenation of therapeutic agents. The purpose of this study was to
investigate the effect of the three common polymorphic variants of hFMO3 (V257M,
E158K and E308G) on the metabolism and clearance of three structurally similar
compounds: tamoxifen (breast cancer medication), clomiphene (infertility
medication) and GSK5182 (antidiabetic lead molecule). For GSK5182, none of the
three variants showed any significant differences in its metabolism when compared
to the wild-type enzyme. In the case of clomiphene, two of the variants, V257M
and E308G, exhibited a significant increase in all the kinetic parameters
measured with nearly two times faster clearance. Finally, for tamoxifen, a mixed
behaviour was observed; E158K variant showed a significantly higher clearance
compared to the wild type, whereas V257M mutation had the opposite effect.
Overall, the data obtained demonstrate that there is no direct correlation
between the SNPs and the metabolism of these three hFMO3 substrates. The
metabolic capacity is both variant-dependent and substrate-dependent and
therefore when testing new drugs or administering already approved therapies,
these differences should be taken into consideration.
PMID- 29959873
TI - MicroRNA-9 inhibits growth and invasion of head and neck cancer cells and is a
predictive biomarker of response to plerixafor, an inhibitor of its target CXCR4.
AB - Head and neck squamous cell carcinomas (HNSCC) are associated with poor morbidity
and mortality. Current treatment strategies are highly toxic and do not benefit
over 50% of patients. There is therefore a crucial need for predictive and/or
prognostic biomarkers to allow treatment stratification for individual patients.
One class of biomarkers that has recently gained importance are microRNA (miRNA).
MiRNA are small, noncoding molecules which regulate gene expression post
transcriptionally. We performed miRNA expression profiling of a cohort of head
and neck tumours with known clinical outcomes. The results showed miR-9 to be
significantly downregulated in patients with poor treatment outcome, indicating
its role as a potential biomarker in HNSCC. Overexpression of miR-9 in HNSCC cell
lines significantly decreased cellular proliferation and inhibited colony
formation in soft agar. Conversely, miR-9 knockdown significantly increased both
these features. Importantly, endogenous CXCR4 expression levels, a known target
of miR-9, inversely correlated with miR-9 expression in a panel of HNSCC cell
lines tested. Induced overexpression of CXCR4 in low expressing cells increased
proliferation, colony formation and cell cycle progression. Moreover, CXCR4
specific ligand, CXCL12, enhanced cellular proliferation, migration, colony
formation and invasion in CXCR4-overexpressing and similarly in miR-9 knockdown
cells. CXCR4-specific inhibitor plerixafor abrogated the oncogenic phenotype of
CXCR4 overexpression as well as miR-9 knockdown. Our data demonstrate a clear
role for miR-9 as a tumour suppressor microRNA in HNSCC, and its role seems to be
mediated through CXCR4 suppression. MiR-9 knockdown, similar to CXCR4
overexpression, significantly promoted aggressive HNSCC tumour cell
characteristics. Our results suggest CXCR4-specific inhibitor plerixafor as a
potential therapeutic agent, and miR-9 as a possible predictive biomarker of
treatment response in HNSCC.
PMID- 29959874
TI - Examination of muscle morphology and neuromuscular function in normal weight and
overfat children aged 7-10 years.
AB - : Neuromuscular function in young overweight/obese (OF) children is not well
described. AIM: This study examined isometric and isokinetic leg extensor
strength, muscle size (mCSA) and tissue composition as measured via echo
intensity (mEI), and motor unit (MU) firing rates in normal weight (NW) and OF
children aged 7-10 years. METHODS: Fourteen NW (eight girls and six boys, BMI:
15.8 +/- 1.4 kg/m2 ) and 15 OF (10 girls and five boys, BMI: 20.8 +/- 2.3 kg/m2 )
children volunteered to perform this study. Percentage body fat (%BF) was
measured, and mCSA, mEI, and subcutaneous fat (sFAT) of the vastus lateralis (VL)
was assessed. MU mean firing rates (MFRs) in relation to recruitment threshold
(RT) of the VL were assessed during submaximal isometric contractions. Maximal
isokinetic contractions were performed at 1.05 and 4.20 rad/s. The 95% confidence
intervals (CI) from the statistical tests are presented. RESULTS: The OF children
had greater %BF (95% CI = -15.1 to -7.2), mCSA (95% CI = -4.1 to -1.2), mEI (95%
CI = -22.3 to -5.9), and sFAT (95% CI = -0.5 to -0.1), greater rate of strength
loss with increasing isokinetic velocities (95% CI = 0.4 to 5.4), and a smaller
range of MFRs (95% CI = 0.007 to 7.136) at the steady torque than the NW
children. CONCLUSIONS: The OF children had poorer muscle tissue composition,
greater velocity-related impairments in muscle strength, and a smaller range of
MFRs at the targeted torque that may suggest altered MU recruitment strategies.
Interventions in OF children should include exercises and recruit higher
threshold MUs, such as high-intensity resistance exercises.
PMID- 29959875
TI - Profiling of hepatic metabolizing enzymes and nuclear receptors in rats with
adjuvant arthritis by targeted proteomics.
AB - Inflammatory conditions alter the expression and activity of factors influencing
pharmacokinetics, such as metabolizing enzymes. The study examined alterations of
hepatic protein levels of cytochrome P450 (CYP), UDP-glucuronosyltransferase
(UGT) and nuclear receptors in rats with adjuvant-induced arthritis (AA rats), an
inflammatory animal model, by liquid chromatography-tandem mass spectrometry
based targeted proteomics. The protein levels of CYP1A1, CYP1A2, CYP2A1, CYP2A3,
CYP2C6, CYP2C12, CYP2D3, CYP2E1, CYP3A9, UGT1A1 and UGT1A2/3 in liver microsomes
of AA rats were significantly lower than those in control rats. The protein
levels of constitutive androstane receptor (CAR) and retinoid X receptor alpha
(RXRalpha) in the cytoplasm and nucleus were also significantly decreased, to
approximately 60% of the control levels. The decreased protein levels of CYP1A2,
CYP2C6, CYP2D3, CYP2E1 and UGT1A1 were potentially associated with downregulation
of CAR or RXRalpha expression in the nucleus.
PMID- 29959876
TI - Hydronephrosis and risk of later development of hypertension.
AB - AIM: Congenital ureteral obstruction is a fairly common condition in infants, and
its clinical management has been long debated during the last decade. The long
term physiological consequences of today's conservative non-surgical management
in many asymptomatic hydronephrotic children are unclear. METHODS: Experimental
studies in rats and mice, retrospective studies in children and adults, as well
as prospective studies in children are included in this mini review. RESULTS:
Experimental models of hydronephrosis in rats and mice have demonstrated that
partial ureteropelvic junction obstruction (UPJO) is casually linked with
development of hypertension and renal injuries in later life. The mechanisms are
multifactorial and involve increased activity of the renin-angiotensin
aldosterone system and renal sympathetic nerve activity. Furthermore, oxidative
stress and nitric oxide deficiency in the affected kidney appear to play
important roles in the development and maintenance of hypertension. Clinical case
reports in adults and recent prospective studies in children have associated
hydronephrosis with elevated blood pressure, which could be reduced by surgical
management of the obstruction. CONCLUSION: Based on current experimental and
clinical knowledge regarding the link between partial UPJO and changes in blood
pressure, it is proposed that today's non-operative management of hydronephrosis
should be reconsidered to reduce the risk of developing elevated blood pressure
or hypertension in later life.
PMID- 29959877
TI - Local prey community composition and genetic distance predict venom divergence
among populations of the northern Pacific rattlesnake (Crotalus oreganus).
AB - Identifying the environmental correlates of divergence in functional traits
between populations can provide insights into the evolutionary mechanisms that
generate local adaptation. Here, we assess patterns of population differentiation
in expressed venom proteins in Northern Pacific rattlesnakes (Crotalus oreganus)
from 13 locations across California. We evaluate the relative importance of major
biotic (prey species community composition), abiotic (temperature, precipitation
and elevation) and genetic factors (genetic distance based on RAD-seq loci) as
correlates of population divergence in venom phenotypes. We found that over half
of the variation in venom composition is associated with among-population
differentiation for genetic and environmental variables and that this variation
occurred along axes defining previously observed functional trade-offs between
venom proteins that have neurotoxic, myotoxic and hemorrhagic effects.
Surprisingly, genetic differentiation among populations was the best predictor of
venom divergence, accounting for 46% of overall variation, whereas differences in
prey community composition and abiotic factors explained smaller amounts of
variation (23% and 19%, respectively). The association between genetic
differentiation and venom composition could be due to an isolation-by-distance
effect or, more likely, an isolation-by-environment effect where selection
against recent migrants is strong, producing a correlation between neutral
genetic differentiation and venom differentiation. Our findings suggest that even
coarse estimates of prey community composition can be useful in understanding the
selection pressures acting on patterns of venom protein expression. Additionally,
our results suggest that factors other than adaptation to spatial variation in
prey need to be considered when explaining population divergence in venom.
PMID- 29959878
TI - The Welch Emotional Connection Screen: validation of a brief mother-infant
relational health screen.
AB - AIM: The Welch Emotional Connection Screen (WECS), assesses mother-infant
Emotional Connection in clinical settings. It includes: Attraction, Vocal
Communication, Facial Communication, Sensitivity/Reciprocity and clinical
decision of Emotional Connection (yes/no). We tested concurrent and construct
validity of the WECS and associations with behavioural and physiological measures
in preterm infants. METHODS: Videos from 76 mothers-infants (gestational age 36
weeks) during an in-NICU caregiving paradigm were coded for maternal caregiving
behaviour. Videos of mothers-infants were also obtained at 4 months during 10
minutes of face-to-face play (coded with WECS and for maternal positivity and
infant social engagement) and the still-face paradigm (coded for infant
behavioural approach towards mother; infant electrocardiogram acquired in vivo).
RESULTS: WECS maternal scores were positively associated with maternal
sensitivity and quality of vocal contact at 36 weeks (caregiving) and maternal
positivity at 4 months (face-to-face). WECS infant scores positively correlated
with infant social engagement and maternal positivity during face-to-face
interactions at 4 months. Infants from emotionally not connected dyads (vs.
emotionally connected dyads) displayed autonomic dysregulation and less approach
seeking behaviour towards mother during interactive/play sessions of the still
face paradigm. CONCLUSION: This preliminary evidence supports the WECS as a valid
screen for rating mother-preterm infant emotional connection associated with
healthier infant biobehavioural stress responding.
PMID- 29959879
TI - Gambogic Acid Inhibits Melanoma through Regulation of miR-199a-3p/ZEB1
Signalling.
AB - Malignant melanoma is an aggressive form of cancer which is highly resistant to
chemotherapy. We have previously found that gambogic acid (GA), a kind of
polyprenylated xanthone, exhibits an antitumour role in melanoma. The study was
designed to investigate novel mechanisms of the antitumour effect of GA in
melanoma cells and implanted nude mice. Gambogic acid significantly decreased
cell viability, increased apoptosis and reduced migration and invasion in A375
cells. In addition, cisplatin-induced cytotoxicity in both A375 and A375/CDDP
cells was increased by GA. The expression of miR-199a-3p was increased by GA in
A375 cells and implanted tumours, and inhibition of miR-199a-3p significantly
prevented GA-induced effect on cell viability, apoptosis, migration, invasion and
cisplatin sensitivity in A375 cells. miR-199a-3p mimics reduced tumour weight and
volume in vivo and decreased cell viability, increased apoptosis and reduced
migration and invasion in vitro. miR-199a-3p expression was decreased in melanoma
tissues and cells, as compared with their controls. miR-199a-3p possessed a
potential binding site in the 3'-UTR of zinc finger E-box binding homeobox
(ZEB1). ZEB1 expression was increased in melanoma tissues and cells, as compared
with their controls. ZEB1 and miR-199a-3p expression was negatively correlated in
melanoma tissues. The expression of ZEB1 was decreased by GA in A375 cells and
implanted tumours, and up-regulation of ZEB1 significantly prevented GA-induced
effect on cell viability, apoptosis, migration, invasion and cisplatin
sensitivity. Down-regulation of ZEB1 reduced tumour weight and volume in vivo and
decreased cell viability, increased apoptosis and reduced migration and invasion
in vitro. We identified the important roles of miR-199a-3p and ZEB1 in melanoma
and elucidated the tumour suppressor function of miR-199a-3p through inhibition
of ZEB1. The results highlight the importance of miR-199a-3p-ZEB1 signalling in
antitumour effect of GA in malignant melanoma and provide novel targets for the
chemotherapy of melanoma.
PMID- 29959880
TI - Risk acceptance of human T-lymphotropic virus infection in solid organ
transplantation-A survey of Atlantic Canadian ambulatory patients.
AB - BACKGROUND: Human T-lymphotropic virus (HTLV) has an estimated prevalence of 12
per 100 000 in the general Canadian population (with higher rates in distinct
groups) and is most commonly transmitted by breast feeding, sexual intercourse,
sharing injection tools, and blood transfusions. A minority of those infected
will develop severe disease. Health Canada mandates that people who are positive
for HTLV are not suitable to be solid organ donors. Given the apparent low
disease burden of HTLV in Canada, we explored HTLV risk tolerance among patients,
in the context of organ transplantations. METHODS: Using telephone, and in-person
questionnaires, we assessed willingness of patients to accept the risk of HTLV
infection in hypothetical scenarios in which they required an organ transplant
for survival. RESULTS: Seventy-four outpatients attending various medical clinics
participated in the survey. In a standard gamble scenario, 37.5% of respondents
would have accepted a solid organ transplant regardless of HTLV risk, as compared
to 27.3% and 24.6% accepting organ transplantation if there was a risk of human
immunodeficiency virus (HIV) or of human virus Y (HVY; a fictitious virus
describing HTLV in terms of neurological outcomes), respectively. Similarly, the
median longevity traded to ensure a virus-free organ was 4-5 years regarding all
viruses, except for HVY, for which the median time exchanged to ensure a virus
free organ was 10 (out of a possible 20) years. CONCLUSIONS: These data suggest
that patients, though willing to accept some risk of viral infection, would not
be willing to forgo HTLV screening of solid organs.
PMID- 29959881
TI - Predicting Pre-transplant Abstinence in Patients with Alcohol-Induced Liver
Disease.
AB - BACKGROUND: Some patients with alcohol-induced liver failure will succumb to
their disease prior to demonstrating compliance with the six months abstinence
rule for liver transplantation. PURPOSE: The purpose of this study was to
determine whether a patient's self-reported, longest period of abstinence
predicts subsequent abstinence. METHODS: Adult patients (n=63) with alcohol
induced liver disease were asked to recall their longest period of abstinence
prior to their initial hepatology visit. Compliance with instructions to remain
abstinent was then documented. RESULTS: Nineteen patients (30%) achieved
abstinence and 44 (70%) relapsed within six months of seeing their hepatologist.
Relapses were more common in patients who self-reported previous periods of
abstinence exceeding six months (19/44, 43%) compared with 2/19 (11%) in those
with periods of less than six months (p=0.01). Serum albumin levels were lower in
relapsers but other tests of liver function (bilirubin level and international
ratio of prothrombin time) and predictors of post-transplant recidivism did not
associate with relapses. On multivariate analysis, self-reported abstinence (OR:
0.11, 95% CI: 0.02-0.57, p=0.008) and serum albumin levels (regression
coefficient 0.113, p=0.02) predicted relapses. CONCLUSIONS: A self-reported
period of abstinence in excess of six months was associated with an increased
risk of subsequent relapse following a hepatologist's instructions to remain
abstinent. These counter-intuitive findings should be confirmed by larger,
prospective studies.
PMID- 29959882
TI - Short and Long Term Mortality Predictors in Octogenarians with Acute Coronary
Syndromes.
AB - PURPOSE: Octogenarians with acute coronary syndromes have higher mortality and
morbidity due to higher prevalence of comorbidities and frailty. The aim of this
study was to explore the predictors of short and long term mortality in
octogenarians with ACS. METHODS: Ninety-eight consecutive octogenarians
presenting with acute coronary syndrome (mean age:84+/-3 years, 56 male) were
included. All patients underwent coronary angiography and were given optimal
medical treatment. The primary end point was cardiovascular mortality in hospital
and at one year. RESULTS: Fifteen patients died during hospitalization and 20
patients died after discharge within the first year. ST-segment-elevation
myocardial infarction and hypotension were significantly more prevalent in the in
hospital mortality group while atrial fibrillation and hyponatremia were more
prevalent in the long-term mortality group. All deceased patients had
significantly lower left ventricular ejection fraction and glomerular filtration
rate. Cox analysis revealed ST-segment-elevation myocardial infarction,
hypotension and left ventricular ejection fraction as independent predictors of
in-hospital mortality while hyponatremia, atrial fibrillation and renal
dysfunction as independent predictors of long term mortality. CONCLUSION: It
would be reasonable to pay further attention to octogenarians with acute coronary
syndrome if they are presenting with ST-segment-elevation myocardial infarction,
and have hypotension, impaired left ventricular function, hyponatremia, atrial
fibrillation or renal dysfunction, which are associated with increased mortality.
PMID- 29959883
TI - Combining the Love of Art, Science, Business and Medicine to Innovate and Enhance
Patient Health. Highlights from the 7th Annual Leaders in Medicine Symposium of
the Cummings School of Medicine, Calgary, AB.
AB - The Leader in Medicine (LIM) Program of the Cumming School of Medicine,
University of Calgary, hosted its 7th Annual LIM Research Symposium on October
30, 2015 and participation grew once again, with a total of six oral and 99
posters presentations! Over 45 of our Faculty members also participated in the
symposium. This year's LIM Symposium theme was "Innovations in Medicine" and the
invited guest speaker was our own Dr. Breanne Everett (MD/MBA). She completed her
residency in plastic surgery at University of Calgary and holds both a medical
degree and an MBA from the University of Calgary. In her inspiring talk, entitled
"Marrying Business and Medicine: Toe-ing a Fine Line", she described how she
dealt with a clinical problem (diabetic foot ulcers), came up with an innovation
that optimized patient care, started her own company and delivered her product to
market to enhance the health of the community. She clearly illustrated how to
complete the full circle, from identifying a clinical problem to developing and
providing a solution that both enhances clinical care and patient health as well
as reduces health care costs and hospital admissions. The research symposium was
an outstanding success and the abstracts are included in companion article in
CIM.
PMID- 29959885
TI - A peculiar reaction curve with dual spikes in absorbance during a total bilirubin
assay in spite of accurate results induced by high M-protein concentration.
PMID- 29959884
TI - Proceedings from the 7th Annual University of Calgary Leaders in Medicine
Research Symposium.
AB - TOn October 30th, 2015, the Leaders in Medicine (LIM) program at the Cumming
School of Medicine, University of Calgary hosted its 7th Annual Research
Symposium. Dr. Breanne Everett, President and CEO of Orpyx Medical Technologies
and holder both of medical and MBA degrees from the University of Calgary,
presented a lecture entitled "Marrying Business and Medicine: Toe-ing a Fine
Line". The LIM symposium also provides a forum for both LIM and non-LIM medical
students to present their research work in oral and poster presentation formats.
This year over 100 students submitted their work and six oral presentations and
99 posters were presented. The oral presentations were as follows: Ryan Lewinson,
Prediction of wedged insole-induced changes to knee joint moments during
walkingLindsey Logan, Robotic measures provide insight on sensorimotor and
cognitive impairments following traumatic brain injury Jackie Mann, What
medication information do community doctors want to receive in discharge
summaries for safer transfers? Ashley Jensen, Increased mortality associated with
resident handoff periods at ten veterans administration medical centers Jason
Bau, Keratinocyte growth factor protects against C. difficile-induced cell injury
and death Michael Keough, A novel drug class promotes regeneration of central
nervous system myelin by overcoming inhibitory scar molecules in vitro and in
vivo For further details on the University of Calgary Leaders in Medicine Program
see "A Prescription that Addresses the Decline of Basic Science Education in
Medical School" (Clinical and Investigative Medicine. 2014;37(5):E29). The LIM
Symposium has the following objectives: (1) to showcase the variety of projects
undertaken by students in the LIM Program as well as University of Calgary
medical students; (2) to encourage medical student participation in research and
special projects; (3) to inform students and faculty about the diversity of
opportunities available for research and special projects during medical school
and beyond; and, (4) to enhance student and staff interactions, with the ultimate
goal being to enhance translational medicine improve health.
PMID- 29959886
TI - No central adrenal insufficiency found in patients with Prader-Willi syndrome
with an overnight metyrapone test.
AB - Background Individuals with Prader-Willi syndrome (PWS) have hypothalamic
dysfunction and may have central adrenal insufficiency (CAI). The prevalence of
CAI in PWS remains unknown. Methods Twenty-one subjects with PWS aged 4-53 years
underwent a low dose adrenocorticotropic hormone (ACTH) stimulation test (LDAST)
(1 MUg/m2, maximum 1 MUg) followed by an overnight metyrapone test (OMT).
Metyrapone (30 mg/kg, maximum 3 g) was administered at 2400 h. Cortisol, 11
deoxycortisol (11-DOC) and ACTH levels were collected the following morning at
0800 h. OMT was the standard test for comparison. Peak cortisol >=15.5 MUg/dL
(427.6 nmol/L) on LDAST and 0800 h 11-DOC >=7 MUg/dL (200 nmol/L) on OMT were
classified as adrenal sufficiency. Results Twenty subjects had 0800 h 11-DOC
values >=7 MUg/dL on OMT indicating adrenal sufficiency. One subject had an
inconclusive OMT result. Six of the 21 (29%) subjects had peak cortisol <15.5
MUg/dL on LDAST. Conclusions We found no evidence of CAI based on OMT, yet 29% of
our PWS population failed the LDAST. This suggests that the LDAST may have a high
false positive rate in diagnosing CAI in individuals with PWS. OMT may be the
preferred method of assessment for CAI in patients with PWS.
PMID- 29959887
TI - Mesenchymal stem cell transplantation and aerobic exercise for Parkinson's
disease: therapeutic assets beyond the motor domain.
AB - Parkinson's disease (PD) is a very common neurodegenerative condition in which
both motor and nonmotor deficits evolve throughout the course of the disease.
Normally characterized as a movement disorder, PD has been broadly studied from a
motor perspective. However, mild to moderate cognitive deficits began to appear
in the early phases of the disease, even before motor disturbances actually
manifest, and continue to progress relentlessly. These nonmotor manifestations
are also a source of detriment to the patients' already strained functionality
and quality of life, and pose a therapeutic challenge seeing that replacing
therapies have had conflicting results. Considering that the currently approved
therapies can hardly be considered curative, efforts to find therapeutic
approaches with an actual disease-modifying quality and capable of addressing not
only motor but also cognitive dysfunctions are clearly needed. Among possible
alternatives with such attribute, mesenchymal stem cell transplantation and
exercise are worth highlighting given their common neuroprotective, neuroplastic,
and immunomodulatory properties. In this paper, we will summarize the existent
literature on the topic, focusing on the mechanisms of action through which these
two approaches might beget therapeutic benefits for PD beyond the commonly
assessed motor dysfunctions, alluding, at the same time, toward a potential
synergic association of both therapies as an optimized approach for PD.
PMID- 29959888
TI - Comparisons of classification methods for viral genomes and protein families
using alignment-free vectorization.
PMID- 29959889
TI - Pain in the hand caused by a previously undescribed mechanism with possible
relevance for understanding regional pain.
AB - Background and aims A previously undescribed mechanism of pain in the ulnar side
of the hand was observed in a series of four patients. All were found to have a
sensitive point in the first interspace of the hand and possible entrapment of a
terminal branch of ulnar nerve piercing the fascia in the first interphalangeal
webspace was suggested. Methods Pressure on the sensitive point reproduced the
ulnar sided hand pain. Diagnostic and therapeutic injection of the mixture of
local anesthetic and corticosteroid were performed. The degree and duration of
relief of pain was noted. Results In individuals with recent onset hand pain of
this type the injections abolished pain for 2 or more years. In individuals with
long-standing pain (longer than 3-6 months) the pain was abolished for periods of
time lasting several hours to several weeks. The correspondence of the point,
where injections were done with acupuncture point LI4 was noted. Conclusions The
location of possible nerve entrapment corresponds with an acupuncture point LI4
and may additionally represent a previously undescribed myofascial trigger point.
Implications The suggested mechanism of ulnar sided hand pain represents a
miniature chronic constriction injury similar to the animal model of neuropathic
pain and may have relevance for regional pain elsewhere in the body.
PMID- 29959892
TI - Evolution and genetic control of the floral ground plan.
AB - Contents Summary 70 I. Introduction 70 II. What is the floral ground plan? 71
III. Diversity and evolution of the floral ground plan 72 IV. Genetic mechanisms
77 V. What's next? 82 Acknowledgements 83 References 83 SUMMARY: The floral
ground plan is a map of where and when floral organ primordia arise. New results
combining the defined phylogeny of flowering plants with extensive character
mapping have predicted that the angiosperm ancestor had whorls rather than
spirals of floral organs in large numbers, and was bisexual. More confidently,
the monocot ancestor likely had three organs in each whorl, whereas the rosid and
asterid ancestor (Pentapetalae) had five, with the perianth now divided into
sepals and petals. Genetic mechanisms underlying the establishment of the floral
ground plan are being deduced using model species, the rosid Arabidopsis, the
asterid Antirrhinum, and in grasses such as rice. In this review, evolutionary
and genetic conclusions are drawn together, especially considering how known
genes may control individual processes in the development and evolution of ground
plans. These components include organ phyllotaxis, boundary formation, organ
identity, merism (the number or organs per whorl), variation in the form of
primordia, organ fusion, intercalary growth, floral symmetry, determinacy and,
finally, cases where the distinction between flowers and inflorescences is
blurred. It seems likely that new pathways of ground plan evolution, and new
signalling mechanisms, will soon be uncovered by integrating morphological and
genetic approaches.
PMID- 29959890
TI - The Prognostic Value of Serum Neuron Specific Enolase (NSE) and S100B Level in
Patients of Acute Spinal Cord Injury.
AB - BACKGROUND The correlation between serum concentration of neuron specific enolase
(NSE), S100B, and the prognosis of patients with acute spinal cord injury (ASCI)
remains controversial. MATERIAL AND METHODS Sixty patients with confirmed
diagnosis of ASCI were recruited for this study from February 2015 to January
2017. The serum level of NSE and S100B were dynamically measured: on the day of
injury and for 2 weeks. The 60 cases were divided into Group A (1 or more than 1
ASIA grade improved at 6 months after the injury) and Group B (ASIA grades
changed <1 at 6 months after the injury). The serum level of the 2 groups were
compared at different time points. And the prognostic value of serum NSE and
S100B as biomarkers in patients with ASCI were calculated by Bayes theorem.
RESULTS The serum levels of NSE in Groups A and B on the 2nd day of injury
reached a peak at 66.80+/-13.76 g/L and 98.87+/-20.12 MUg/L, respectively, and
then declined gradually. On the 14th day of injury, the serum levels of NSE in
both groups were 21.23+/-8.45 and 39.32+/-16.31 MUg/L, respectively, which were
much lower than those on the 2nd day (P<0.05). The serum levels of S100B in
Groups A and B rose after the injury and reached a peak on the 4th day of injury.
Then, the levels declined gradually to 1.14+/-0.64 and 1.97+/-0.98 MUg/L,
respectively, 2 weeks after the injury. Serum levels of NSE and S100B were good
biomarkers for predicting the prognosis of ASCI patients with the sensitivity of
74.35% and 71.79%, the specificity of 71.43% and 66.67%. The cutoff value for
serum NSE and S100B were 29.07 MUg/L and 1.67 MUg/L respectively. The AUCs were
0.78 (95% CI: 0.66-0.89) and 0.76 (95% CI: 0.63-0.89) respectively for serum NSE
and S100B. CONCLUSIONS Serum levels of NSE and S100B protein can reflect the
degree of spinal cord injury and could be potential biomarkers for the prognosis
of acute spinal cord injury.
PMID- 29959891
TI - Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a
protease-activated receptor 1- and protease-activated receptor 4-dependent
mechanism.
AB - BACKGROUND AND PURPOSE: Thrombin is massively released upon tissue damage
associated with bleeding or chronic inflammation. The effects of this thrombin on
tissue regrowth and repair has been scarcely addressed and only in cancer cell
lines. Hence, the purpose of the present study was to determine thrombin's
pharmacological effects on human intestinal epithelium growth, proliferation and
apoptosis, using three-dimensional cultures of human colon organoids.
EXPERIMENTAL APPROACH: Crypts were isolated from human colonic resections and
cultured for 6 days, forming human colon organoids. Cultured organoids were
exposed to 10 and 50 mU.mL-1 of thrombin, in the presence or not of protease
activated receptor (PAR) antagonists. Organoid morphology, metabolism,
proliferation and apoptosis were followed. KEY RESULTS: Thrombin favoured
organoid maturation leading to a decreased number of immature cystic structures
and a concomitant increased number of larger structures releasing cell debris and
apoptotic cells. The size of budding structures, metabolic activity and
proliferation were significantly reduced in organoid cultures exposed to
thrombin, while apoptosis was dramatically increased. Both PAR1 and PAR4
antagonists inhibited apoptosis regardless of thrombin doses. Thrombin-induced
inhibition of proliferation and metabolic activity were reversed by PAR4
antagonist for thrombin's lowest dose and by PAR1 antagonist for thrombin's
highest dose. CONCLUSIONS AND IMPLICATIONS: Overall, our data suggest that the
presence of thrombin in the vicinity of human colon epithelial cells favours
their maturation at the expense of their regenerative capacities. Our data point
to thrombin and its two receptors PAR1 and PAR4 as potential molecular targets
for epithelial repair therapies.
PMID- 29959893
TI - A genetic screen for plant mutants with altered nodulation phenotypes in response
to rhizobial glycan mutants.
AB - Nodule primordia induced by rhizobial glycan mutants often remain uninfected. To
identify processes involved in infection and organogenesis we used forward
genetics to identify plant genes involved in perception and responses to
bacterial glycans. To dissect the mechanisms underlying the negative plant
responses to the Mesorhizobium loti R7AexoU and ML001cep mutants, a screen for
genetic suppressors of the nodulation phenotypes was performed on a chemically
mutagenized Lotus population. Two mutant lines formed infected nitrogen-fixing
pink nodules, while five mutant lines developed uninfected large white nodules,
presumably altered in processes controlling organogenesis. Genetic mapping
identified a mutation in the cytokinin receptor Lhk1 resulting in an alanine to
valine substitution adjacent to a coiled-coil motif in the juxta-membrane region
of LHK1. This results in a spontaneous nodulation phenotype and increased
ethylene production. The allele was renamed snf5, and segregation studies of snf5
together with complementation studies suggest that snf5 is a gain-of-function
allele. This forward genetic approach to investigate the role of glycans in the
pathway synchronizing infection and organogenesis shows that a combination of
plant and bacterial genetics opens new possibilities to study glycan responses in
plants as well as identification of mutant alleles affecting nodule
organogenesis.
PMID- 29959894
TI - MicroRNAs in Marchantia polymorpha.
AB - Contents Summary 409 I. Introduction 409 II. RNA silencing machinery in
Marchantia polymorpha 410 III. miRNA prediction by integrating omics approach 410
IV. miRNAs and their targets in Marchantia polymorpha 410 V. Mpo-miR390-mediated
MpTAS3 tasiRNA biogenesis and potential tasiARF target MpARF2 414 VI. Artificial
miRNA and CRISPR-CAS9 edited MIR gene in Marchantia polymorpha 414 VII.
Conclusions 415 Acknowledgements 415 References 415 SUMMARY: The liverwort
Marchantia polymorpha occupies an important phylogenetic position for comparative
studies of land plant gene regulation. Multiple gene regulatory pathways mediated
by small RNAs, including microRNAs (miRNAs), trans-acting short-interfering RNAs,
and heterochromatic siRNAs often associated with RNA-dependent DNA methylation,
have been characterized in flowering plants. Genes for essential components for
all of these small RNA-mediated gene silencing pathways are found in M.
polymorpha as well as the moss Phsycomitrella patens, indicating that these
pathways existed in the ancestral land plant. However, only seven miRNAs are
conserved across land plants, with both ancestral and novel targets identified in
M. polymorpha. There is little or no evidence that any of these conserved miRNAs
are present in algae. As with other plants investigated, most miRNAs in M.
polypmorpha exhibit lineage-specific evolution. Application of artificial miRNA
and CRISPR-Cas9 technologies in genetic studies of M. polymorpha provide avenues
to further investigate miRNA biology.
PMID- 29959895
TI - Epigenetic regulation of anthocyanin biosynthesis by an antagonistic interaction
between H2A.Z and H3K4me3.
AB - The accumulation of anthocyanins in response to specific developmental cues or
environmental conditions plays a vital role in plant development and protection
against stresses. Extensive research has examined the regulation of anthocyanin
biosynthetic genes at the transcriptional and post-transcriptional levels, but
the role of chromatin in this regulation remains unknown. Chromatin
immunoprecipitation and quantitative reverse transcription-polymerase chain
reaction (qRT-PCR) analyses were performed. Genetic interactions between
trimethylation of lysine 4 on histone H3 (H3K4me3) and the chromatin remodeling
complex SWR1 in the control of anthocyanin biosynthesis were further studied. In
this study, we provide evidence that a conserved histone H2 variant, H2A.Z,
negatively regulates anthocyanin accumulation through deposition at a set of
anthocyanin biosynthetic genes and consequently represses their expression in
Arabidopsis thaliana. Our data indicate that the accumulation of anthocyanin in
H2A.Z deposition-deficient mutants is associated with increased H3K4me3, which is
required for promotion of the expression of anthocyanin biosynthetic genes. We
further provide evidence that H3K4me3 in anthocyanin biosynthetic genes is
negatively associated with the presence of H2A.Z. Our results reveal an
antagonistic relationship between H2A.Z and H3K4me3 in the regulation of the
expression of anthocyanin biosynthesis genes, adding another layer of regulation
to anthocyanin biosynthesis genes and highlighting the role of chromatin in gene
regulation.
PMID- 29959896
TI - The value of wet leaves.
AB - Contents Summary 1156 I. Introduction 1156 II. How often are leaves wet? 1157
III. The costs of leaf wetting 1157 IV. The real and potential benefits of leaf
wetting 1161 V. Wet leaves: costs, benefits and tradeoffs in a changing world
1165 Acknowledgements 1166 References 1166 SUMMARY: An often-overlooked feature
of all plants is that their leaf surfaces are wet for significant periods over
their lifetimes. Leaf wetting has a number of direct and indirect effects on
plant function from the scale of the leaf to that of the ecosystem. The costs of
leaf wetting for plant function, such as the growth of pathogens and the leaching
of nutrients, have long been recognized. However, an emerging body of research
has also begun to demonstrate some very clear benefits. For instance, leaf
wetting can improve plant-water relations and lead to increased photosynthesis.
Leaf wetting may also lead to synergistic effects on plant function, such as when
leaf water potential improvements lead to enhanced growth that does not occur
when plant leaves are dry. We identify important reasons why leaf wetting can be
critical for plant sciences to not only acknowledge, but also directly address,
in future research. To do so, we provide a framework for the consideration of the
relative balance of the various costs and benefits resulting from leaf wetting,
as well as how this balance may be expected to change given projected scenarios
of global climate change in the future.
PMID- 29959897
TI - Tumor necrosis factor-alpha and diabetic retinopathy: Review and meta-analysis.
AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is produced by multinuclear
giant cells and acts as local intensification signals in pathological processes
associated with chronic eye inflammation. This meta-analysis was performed to
provide a better understanding of the relationship between TNF-alpha and diabetic
retinopathy (DR). METHOD: Online electric databases were searched to retrieve all
relevant articles published before October 2017. The standard mean difference
(SMD) and their 95% confidence intervals (CI) were included and then pooled with
a random effects model. RESULTS: A total of 16 articles with 1286 participants
were included in this meta-analysis. No difference in the level of TNF-alpha was
found between DR patients and healthy controls (SMD = 0.39, 95% CI = -0.09 to
0.68, P = 0.01). Subgroup analysis showed that with respect to the level of TNF
alpha, the association was significant for studies conducted in Europe (SMD:
0.57, 95% CI: 0.11-1.02, P = 0.01), patients with type 1 DM (SMD: 1.06, 95% CI:
0.09-2.04, P = 0.03), studies based on serum samples (SMD: 0.57, 95% CI: 0.12
1.02, P = 0.01) and studies with a sample size >50 (SMD: 0.39, 95% CI: 0.03-0.75,
P = 0.04). CONCLUSION: The results this meta-analysis indicated that the level of
TNF-alpha in DR patients was significantly different from that in the healthy
controls, so TNF-alpha represents a candidate biomarker for DR.
PMID- 29959898
TI - VEST and Interpretation of a Randomized Controlled Trial.
PMID- 29959899
TI - Historical Milestones in the Management of Stable Coronary Artery Disease over
the Last Half Century.
AB - Coronary revascularization for coronary artery disease dates back to the
introduction of coronary bypass by Favaloro in 1967 and coronary angioplasty by
Gruentzig in 1977 (first published in 1968 and 1978, respectively). There have
been many technical improvements over the ensuing 5 decades, studied in clinical
trials. This article reviews the history of coronary revascularization (the
development of optimal medical therapy) and points the way to the future of
stable coronary artery disease management.
PMID- 29959900
TI - The Role of the Environment in Health Outcomes.
PMID- 29959901
TI - One-year adolescent bone mineral density and bone formation marker changes
through the use or lack of use of combined hormonal contraceptives.
AB - OBJECTIVE: The objective of this study was to evaluate the effects of two low
dose combined oral contraceptives on bone metabolism in adolescents for one year.
METHODS: This was a quasi-experimental study. The adolescents were divided into
three groups: oral contraceptives 1 (n=42) (20MUg EE/150MUg desogestrel), oral
contraceptives 2 (n=66) (30MUg EE/3mg drospirenone), and a control group (n=70).
Adolescents underwent anthropometric assessment and densitometry (dual-energy X
ray). Bone age and bone formation markers (osteocalcin and bone alkaline
phosphatase) were evaluated. The oral contraceptives users were evaluated again
after 12 months. Linear regression analysis was used to indirectly study the
effect of each additional year of chronological age on anthropometric and
densitometric variables as well as on bone markers in the control group. RESULTS:
At study entry, no significant differences were observed between the oral
contraceptives 1, oral contraceptives 2, and controls in the analyzed variables.
Linear regression analysis showed an increase in bone mineral density and bone
mineral content for each additional year. There was a significant reduction in
bone alkaline phosphatase levels; no significant difference was observed for
osteocalcin in control individuals. Comparison of dual-energy X-ray variables at
baseline and after one year showed no significant differences in the oral
contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone
alkaline phosphatase and osteocalcin levels was observed in both the oral
contraceptives 1 and oral contraceptives 2 groups. CONCLUSION: Adolescent women
gain peak bone mass during this phase of life. Two low-dose combined oral
hormonal contraceptives were associated with lower bone gain and lower bone
formation markers than in untreated controls.
PMID- 29959902
TI - ERICA: smoking is associated with more severe asthma in Brazilian adolescents.
AB - OBJECTIVE: To investigate the association between smoking and asthma, and
possible associated factors in Brazilian adolescents. METHODS: A cross-sectional,
national, school-based study with adolescents aged 12-17 years, participants in
the Study of Cardiovascular Risks in Adolescents (Estudo de Riscos
Cardiovasculares em Adolescentes - ERICA). A total of 66,394 participants
answered a self-administered questionnaire with questions about asthma, smoking,
lifestyle and sociodemographic variables. Bivariate analysis between Current
Asthma (CA) and Severe Asthma (SA) and the other study variables were performed
using Chi-squared. Then, the crude and adjusted Prevalence Ratios (PR), and
respective 95% Confidence Intervals (95% CI) of current asthma/severe asthma and
smoking variables, corrected for sociodemographic and lifestyle variables, were
estimated using generalized linear models with Poisson regression, logit link,
and robust variance. RESULTS: The prevalence of current asthma and severe asthma
were significantly higher in adolescents who were exposed to: experimentation
(current asthma: PR=1.78, 95% CI: 1.51-2.09; severe asthma: PR=2.01; 95% CI: 1.35
2.98); current smoking (current asthma: PR=2.08, 95% CI: 1.65-2.64; severe
asthma: PR=2.29; 95% CI: 1.38-3.82); regular smoking (current asthma: PR=2.25,
95% CI: 1.64-3.07; severe asthma: PR: 2.41; 95% CI: 1.23-4.73); and passive
smoking (current asthma: PR=1.47, 95% CI: 1.27-1.67; severe asthma: PR=1.66; 95%
CI: 1.19-2.32); these associations remained significant after adjustment.
CONCLUSIONS: Asthma and smoking were significantly associated in Brazilian
adolescents, regardless of the sociodemographic and lifestyle factors, notably in
those with more severe disease.
PMID- 29959903
TI - In silico analysis of putative dormancy genes in Plasmodium vivax.
AB - Plasmodium vivax is the most widely spread species causing human malaria. The
control of malaria caused by P. vivax has been largely hampered by its ability to
develop a dormant liver stage that can generate a new blood infection at
different periods of time. Unfortunately, the mechanisms of dormancy in P. vivax
have not been thoroughly elucidated to date. In this study, the putative dormancy
genes were analyzed to select genes with less genetic variability to maintain the
function of relapsing. Expression data concerning these genes were searched to
support the selection. Protein interactions among selected gene products were
identified based on known and predicted protein-protein interaction using String
database. Potentially interacting proteins (n = 15) were used to propose a
mechanism involved in dormancy based on the differential vesicular transport due
to the iron available in the hepatocyte.
PMID- 29959904
TI - Antimicrobial Resistance and Respiratory Infections.
AB - Since their introduction into health care and clinical practice in the early 20th
century, antibiotics have revolutionized medicine. Alarmingly, these drugs are
increasingly threatened by bacteria that have developed a broad diversity of
resistance mechanisms. Antibiotic resistance can be transferred between bacteria,
often on mobile genetic elements; be acquired from the environment; or arise
through mutation because of selective pressures of the drugs themselves. There
are various strategies to resistance, including active efflux of the drug from
the bacterial cell, reduced permeability of the cell envelope, alteration of the
drug's target within the bacterial cell, and modification or destruction of the
antibiotic. Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas
aeruginosa, and Mycobacterium tuberculosis frequently are implicated in
respiratory infections, often manifesting with reduced susceptibility to multiple
classes of antibiotics. Some mechanisms of resistance, such as the beta
lactamases that confer resistance to penicillins and related drugs, have been
well characterized and are widespread in clinical isolates. Other newly
identified determinants, including the colistin resistance gene mcr-1, are
spreading rapidly worldwide and threaten last-resort treatments of multidrug
resistant organisms. Various approaches to detecting antibiotic resistance
provide surveys of the determinants that are available for transfer into
pathogenic bacteria. Together with molecular characterization of newly identified
mechanisms, this surveillance can target drug discovery efforts and increase
antibiotic stewardship. A greater understanding of the mechanisms of antibiotic
resistance in respiratory pathogens combined with rapid diagnostics ultimately
will reduce treatment failure due to inappropriate antibiotic use and prevent
further spread of resistance.
PMID- 29959905
TI - Antimicrobial and anti-inflammatory activities of chemokine CXCL14-derived
antimicrobial peptide and its analogs.
AB - CXCL14 is a CXC chemokine family that exhibits antimicrobial activity and
contains an amphipathic cationic alpha-helical region in the C-terminus, a
characteristic structure of antimicrobial peptides (AMPs). In this study, we
designed three analogs of CXCL1459-75 (named CXCL14-C17) corresponding to the C
terminal alpha-helix of CXCL14, which displayed potential antimicrobial activity
against a wide variety of gram-negative and gram-positive bacteria with minimum
inhibitory concentrations of 4-16 MUM without mammalian cell toxicity.
Furthermore, two CXCL14-C17 analogs (CXCL14-C17-a1 and CXCL14-C17-a3) with
improved cell selectivity were engineered by introducing Lys, Arg, or Trp in
CXCL14-C17. Additionally, CXCL14-C17 analogs showed much greater synergistic
effect (FICI: 0.3125-0.375) with chloramphenicol and ciprofloxacin against
multidrug-resistant Pseudomonas aeruginosa (MDRPA) than LL-37 did (FICI: 0.75
1.125). CXCL14-C17 analogs were more active against antibiotic-resistant bacteria
including methicillin-resistant Staphylococcus aureus (MRSA), MDRPA, and
vancomycin-resistant Enterococcus faecium (VREF) than LL-37 and melittin. In
particular, CXCL14-C17-a2 and CXCL14-C17-a3 completely inhibited the biofilm
formation at sub-MIC and all of the peptides were able to eliminate pre-formed
biofilm as well. Membrane depolarization, flow cytometry, sytox green uptake,
ONPG hydrolysis and confocal microscopy revealed the possible target of the
native peptide (CXCL14-C17) to likely be intracellular, and the amphipathic
designed analogs targeted the bacterial membrane. CXCL14-C17 also showed DNA
binding characteristic activity similar to buforin-2. Interestingly, CXCL14-C17
a2 and CXCL14-C17-a3 effectively inhibited the production and expression of
nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and
monocyte chemoattractant protein (MCP)-1 from lipopolysaccharide (LPS)-stimulated
RAW264.7 cells, suggesting that these peptides could be promising anti
inflammatory and antimicrobial agents.
PMID- 29959906
TI - Women with Hidradenitis Suppurativa Have an Elevated Risk of Suicide.
PMID- 29959907
TI - Pyruvate Protects against Cellular Senescence through the Control of
Mitochondrial and Lysosomal Function in Dermal Fibroblasts.
AB - Mitochondrial dysfunction can drive cellular senescence, which is accompanied by
changes in metabolism and increases in senescence-associated secretory
phenotypes. Although pyruvate, a key metabolite for numerous aspects of
metabolism, has been used as general supplement in synthetic media, the
physiological function of pyruvate underlying its protective role against
cellular senescence under normal conditions has remained unknown. Here, we show
that extracellular pyruvate prevents senescence in normal human dermal
fibroblasts through increasing the generation of oxidized nicotinamide adenine
dinucleotide (NAD+) during the conversion to lactate. Acetylated peroxisome
proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), vacuolar
type H+-ATPaseV0A1 (v-ATPaseV0A1), NF-kappaB p65 subunit (RelA), and histone H3
accumulate under pyruvate deprivation conditions, resulting in the onset of
senescence in normal human dermal fibroblasts through the accumulation of
abnormal mitochondria generated by lysosomal inactivation-induced mitophagy
defects, and through an increase in senescence-associated secretory phenotypes.
Furthermore, pyruvate showed a protective effect against aging phenotypes in skin
equivalents, which consist of a dermis and epidermis that act similarly to in
vivo skin tissues. Our findings reveal a connection between pyruvate and
mitochondrial dysfunction in the progression of senescence that is, to our
knowledge, previously unreported. These results suggest that the pyruvate
deprivation-induced senescence model can be used to study the connection between
metabolism and senescence under normal conditions.
PMID- 29959909
TI - Development of a mass spectrometry-based tryptophan 2, 3-dioxygenase assay using
liver cytosol from multiple species.
AB - A novel and rapid method to determine the potency of inhibitors for tryptophan 2,
3-dioxygenase (TDO2) activities in human and preclinical species was successfully
developed and validated utilizing LC-MS/MS. Previously reported TDO2 activity
assays are resource intensive, requiring cloning and overexpression of TDO2.
Here, we demonstrated that liver cytosol contained sufficient active TDO2 for
evaluating the potency of TDO2 inhibitors across multiple species. TDO2
expression in human cytosol was estimated by LC-MS/MS to be 41 pmoL/mg cytosolic
protein, with similar levels in dogs and monkeys, whereas mice and rats had 9.6
and 5.0-fold greater expression, respectively. Reaction conditions for TDO2
mediated conversion of l-tryptophan to kynurenine were optimized. Marked
differences in kinetic parameters and inhibition potency were observed in TDO2
across species, with different Km values in dog (0.055 mM), monkey (0.070 mM),
human (0.19 mM), mouse (0.32 mM) and rat (0.36 mM). Subsequently, IC50 values
were determined for a series of TDO2 inhibitors in liver cytosol of five species,
and good agreement with the literature values was observed for human enzyme.
Taken together, these data indicate that TDO2 inhibition can be rapidly
determined in readily available hepatic cytosol to assess potential species
differences in potency.
PMID- 29959908
TI - MANF protects dopamine neurons and locomotion defects from a human alpha
synuclein induced Parkinson's disease model in C. elegans by regulating ER stress
and autophagy pathways.
AB - Many studies have demonstrated that mesencephalic astrocyte-derived neurotrophic
factor (MANF) has been shown protective effects on neurotoxin based models of
Parkinson's disease (PD). It still remains unclear whether MANF can rescue
dopaminergic (DA) neurons in an alpha-synuclein model. Glial cell line-derived
neurotrophic factor (GDNF) and its related neurturin (NRTN) can protect DA
neurons in the neurotoxin but not alpha-synuclein animal models of PD, it failed
in the clinical trials. Since alpha-synuclein model can better mimic the
progression of human PD, in our study we overexpressed MANF specifically in DA
neurons by using an alpha-synuclein Caenorhabditis elegans (C. elegans) model.
Our results showed MANF alleviated progressive neuronal degeneration and
prevented locomotion defects. Indeed, MANF can protect cilia of DA neurons at an
early stage, suggested that MANF participated in the whole process of neuronal
degeneration. Furthermore, we found MANF facilitated the removal of misfolded
alpha-synuclein proteins and rescued the function of damaged DA neurons. By using
RNAi approach, we inhibited ER stress and autophagy related genes and effects of
MANF were decreased, which demonstrated ER stress and autophagy pathways were
involved in the MANF-mediated neuroprotection. Our study suggests MANF exhibits
potential as a neuroprotective agent for PD therapy.
PMID- 29959910
TI - Reduce the burden of dementia now.
PMID- 29959911
TI - ARF promotes the degradation of the Epidermal Growth Factor Receptor by the
lysosome.
AB - Epidermal Growth Factor Receptor (EGFR) signaling regulates multiple cellular
processes including proliferation, survival and apoptosis, and is attenuated by
lysosomal receptor degradation. EGFR is a potent oncogene and activating
mutations of EGFR are critical determinants of oncogenic transformation as well
as therapeutic targets in non-small cell lung cancer. We previously demonstrated
that wild type and mutant EGFRs repress the expression of the ARF tumor
suppressor to promote the survival of lung tumor cells. In this study, using
transient transfection systems in CHO EGFR-null cells as well as in various lung
tumor cell lines carrying wild type or activated mutant EGFR, we show that ARF
downregulates the expression of EGFR protein by reducing its half life. In wild
type EGFR cells, ARF promotes canonical lysosomal degradation of the receptor
through enhanced phosphorylation of EGFR-Y1045 and Cbl-Y731. In contrast, in
mutant EGFR cells, ARF induces EGFR degradation by activating a non-canonical AKT
dependent lysosomal pathway. Taken together, these results uncover a feedback
loop by which ARF may control EGFR turnover to restrain oncogenic signaling. They
also highlight distinct degradation promoting pathways between wild type and
mutant EGFRs in response to ARF.
PMID- 29959912
TI - SAHA and cisplatin sensitize gastric cancer cells to doxorubicin by induction of
DNA damage, apoptosis and perturbation of AMPK-mTOR signalling.
AB - Chemotherapy remains the most prescribed anti-cancer therapy, despite patients
suffering severe side effects and frequently developing chemoresistance. These
complications can be partially overcome by combining different chemotherapeutic
agents that target multiple biological pathways. However, selecting efficacious
drug combinations remains challenging. We previously used fission yeast
Schizosaccharomycespombe as a surrogate model to predict drug combinations, and
showed that suberoylanilide hydroxamic acid (SAHA) and cisplatin can sensitise
gastric adenocarcinoma cells toward the cytotoxic effects of doxorubicin. Yet,
how this combination undermines cell viability is unknown. Here, we show that
SAHA and doxorubicin markedly enhance the cleavage of two apoptosis markers,
caspase 3 and poly-ADP ribose polymerase (PARP-1), and increase the
phosphorylation of gammaH2AX, a marker of DNA damage. Further, we found a
prominent reduction in Ser485 phosphorylation of AMP-dependent protein kinase
(AMPK), and reductions in its target mTOR and downstream ribosomal protein S6
phosphorylation. We show that SAHA contributes most of the effect, as confirmed
using another histone deacetylase inhibitor, trichostatin A. Overall, our results
show that the combination of SAHA and doxorubicin can induce apoptosis in gastric
adenocarcinoma in a synthetically lethal manner, and that fission yeast offers an
efficient tool for identifying potent drug combinations against human cancer
cells.
PMID- 29959913
TI - Expression, purification and characterization of an active C491G variant of
ferredoxin sulfite reductase from Synechococcus elongatus PCC 7942.
AB - Recently developed molecular wire technology takes advantage of [4Fe-4S] clusters
that are ligated by at least one surface exposed Cys residue. Mutagenesis of this
Cys residue to a Gly opens an exchangeable coordination site to a corner iron
atom that can be chemically rescued by an external thiolate ligand. This ligand
can be subsequently displaced by mass action using a dithiol molecular wire to
tether two redox active proteins. We intend to apply this technique to tethering
Photosystem I to ferredoxin sulfite reductase (FdSiR), an enzyme that catalyzes
the six-electron reduction of sulfite to hydrogen sulfite and nitrite to ammonia.
The enzyme contains a [4Fe-4S]2+/1+ cluster and a siroheme active site. FdSiRWT
and an FdSiRC491G variant were cloned from Synechococcus elongatus PCC 7942 and
expressed along with the cysG gene from Salmonella typhimurium using the pCDFDuet
plasmid. UV/Vis absorbance spectra of both FdSiRWT and the FdSiRC491G variant
displayed characteristic peaks at 278, 392 (Soret), 585 (alpha) and 714 nm
(charge transfer band), and 278, 394 (Soret), 587 (alpha) and 714 nm (charge
transfer band) respectively. Both enzymes in their as-isolated forms displayed an
EPR spectrum characteristic of an S = 5/2 high spin heme. When reduced, both
enzymes exhibited the signal of a low spin S = 1/2 [4Fe-4S]1+ cluster. The
FdSiRWT and FdSiRC491G variant both showed activity using reduced methyl viologen
and Synechococcus elongatus PCC 7942 ferredoxin 1 (Fd1) as electron donors. Based
on these results, the FdSIRC491G variant should be a suitable candidate for
wiring to Photosystem I.
PMID- 29959914
TI - Synthetic DNA system for structure-function studies of the high affinity CO2
uptake NDH-13 protein complex in cyanobacteria.
AB - The CO2-concentrating mechanism (CCM) in cyanobacteria supports high rates of
photosynthesis by greatly increasing the concentration of CO2 around the major
carbon fixing enzyme, Rubisco. However, the CCM remains poorly understood,
especially in regards to the enigmatic CO2-hydration enzymes which couple
photosynthetically generated redox energy to the hydration of CO2 to bicarbonate.
This CO2-hydration reaction is catalysed by specialized forms of NDH-1 thylakoid
membrane complexes that contain phylogenetically unique extrinsic proteins that
appear to couple CO2 hydration to NDH-1 proton pumping. The development of the
first molecular genetic system to probe structure-function relationships of this
important enzyme system is described. A CO2-hydration deficient strain was
constructed as a recipient for DNA constructs containing different forms of the
CO2-hydration system. This was tested by introducing a construct to an ectopic
location that gives constitutive expression, rather than native inducible
expression, of the ndhF3-ndhD3-cupA-cupS, (cupA operon) encoding high affinity
CO2-hydration complex, NDH-13. Uptake assays show the restoration of high
affinity for CO2 uptake, but demonstrate that the CupA complex can drive only
modest uptake fluxes, underlining the importance of its tandem operation with the
CupB-containing complex NDH-14, the complementary high flux, low affinity CO2
hydration system. Experiments with the carbonic anhydrase inhibitor,
ethoxyzolamide, indicate that the NDH-13 complex is strongly inhibited, yet the
remaining NDH-14 activity in the wild-type is less so, suggesting structural
differences between the low affinity and high affinity CO2-hydration systems.
This new construct will be an important tool to study and better understand
cyanobacterial CO2 uptake systems.
PMID- 29959915
TI - Evaluating rodent experimental models for studies of Blastocystis ST1.
AB - Blastocystis is a common inhabitant of the human gut, colonizing at least one
billion people at a prevalence ranging from <10% to 100% in healthy human
populations globally. The majority of carriers remain asymptomatic, suggesting
that Blastocystis is largely a commensal, though Blastocystis has also been
implicated in disease in some people. However, there are no in vivo model systems
in which to experimentally test the impact of Blastocystis on mammalian hosts and
the gut ecosystem and determine which factors underlie these variable clinical
outcomes. We evaluated a rat model for sustaining of a human-derived Blastocystis
ST1 and assess colonization success and longevity. Because of the broad host
range of Blastocystis, we compared the rat with three other rodent species to
establish the reproducibility of our method. Blastocystis was introduced by
esophageal gavage and colonization success evaluated by Blastocystis culture.
Culture was also used to determine that all animals were negative prior to
colonization and negative controls remain Blastocystis-free. In this study,
Blastocystis ST1 established in 100% of the outbred rats (Rattus norvegicus) and
gerbils (Meriones unguiculatus) challenged. Rats were colonized asymptomatically
for more than one year, but Blastocystis ST1 was not transmitted between rats.
Mus musculus strain CD1 and Mastomys coucha were not susceptible to Blastocystis
ST1. Thus, rats appear to be a suitable in vivo model for studies of Blastocystis
ST1, as do gerbils though testing was less extensive. This work lays the
foundation for experimental work on the role of Blastocystis in health and
disease.
PMID- 29959916
TI - Host specificity and age-dependent resistance to Cryptosporidium avium infection
in chickens, ducks and pheasants.
AB - Host- and age-specificity of Cryptosporidium avium were studied in 1-, 21- and
365-day-old chickens (Gallus gallus), domestic ducks (Anas platyrhynchos) and
ring-necked pheasants (Phasianus colchicus) under experimental conditions.
Cryptosporidium avium was not infectious for ring-necked pheasants, but it was
infectious for ducks and chickens at all age categories. The course of infection
in ducks did not differ among age categories, but 365-day-old chickens had less
severe infections than 1- and 21-day-old chickens. The patent period in chickens
and ducks was >30 DPI, but ducks started to shed oocysts of C. avium earlier (5-6
DPI) and at a lower intensity (accumulated value of infection intensity of 58,000
65,000 OPG) than chickens (9-11 DPI and accumulated value of infection intensity
of 100,000-105,000 OPG). Experimentally infected birds showed no clinical signs
of cryptosporidiosis.
PMID- 29959917
TI - Screening and identification of potential protein biomarkers for evaluating the
efficacy of intensive therapy in pulmonary tuberculosis.
AB - This research aimed to discover potential biomarkers for evaluating the
therapeutic efficacy of intensive therapy in pulmonary tuberculosis (TB). Protein
profiles in 2-months intensively treated TB patients, untreated TB patients, and
healthy controls were investigated with iTRAQ-2DLC-MS/MS technique. 71
differential proteins were identified in 2-months intensively treated TB
patients. Significant differences in complement component C7 (CO7),
apolipoprotein A-IV (APOA4), apolipoprotein C-II (APOC2), and angiotensinogen
(ANGT) were found by ELISA validation. CO7 and ANGT were also found significantly
different in sputum negative patients, compared with sputum positive patients
after intensive treatment. Clinical analysis showed that after 2-months intensive
treatment several indicators were significantly changed, and the one-year cure
rate of sputum negative patients were significantly higher than sputum positive
patients. Diagnostic models consisting of APOC2, CO7 and APOA4 were established
to distinguish intensively treated TB patients from untreated TB patients and
healthy controls with the AUC value of 0.910 and 0.935. Meanwhile, ANGT and CO7
were combined to identify sputum negative and sputum positive TB patients after
intensive treatment with 89.36% sensitivity, 71.43% specificity, and the AUC
value of 0.853. The results showed that APOC2, CO7, APOA4, and ANGT may be
potential biomarkers for evaluating the efficacy of intensive anti-TB therapy.
PMID- 29959918
TI - MagT1 is essential for Drosophila development through the shaping of Wingless and
Decapentaplegic signaling pathways.
AB - Magnesium transporter subtype 1 (MagT1) is a magnesium membrane transporter with
channel like properties. We have previously identified MagT1 (CG7830) in
Drosophila genome and characterized its protein product by electrophysiological
means. Here, we report the generation of fly MagT1 mutants and show that MagT1 is
essential for early embryonic development. In wings and primordial wings, by
clonal analysis and RNAi knock down of MagT1, we have found that loss of MagT1
results in enhanced/ectopic Wingless (Wg, a fly Wnt) signaling and disrupted
Decapentaplegic (Dpp) signaling, indicating the crucial role of MagT1 for fly
development at later stages. Finally, we demonstrate directly that magnesium
transportations are proportional with the MagT1 expressional levels in Drosophila
S2 cells. Taken together, these findings may suggest that MagT1 is a major
magnesium transporter/channel profoundly involved in fly development by affecting
developmental signaling pathways, such as Wg and Dpp signaling.
PMID- 29959919
TI - LncRNA EPIC1 protects human osteoblasts from dexamethasone-induced cell death.
AB - Dexamethasone (Dex) can induce injury to human osteoblasts. Long non-coding RNA
(LncRNA) EPIC1 (Lnc-EPIC1) is a novel Myc-interacting LncRNA. Its effect on Dex
treated human osteoblasts is studied here. In OB-6 osteoblastic cells and primary
human osteoblasts, treatment with Dex increased expression of Lnc-EPIC1. Its
expression is also elevated in the necrotic femoral head tissues of Dex-taking
patients. Ectopic overexpression of Lnc-EPIC1 inhibited Dex-induced apoptosis and
programmed necrosis in OB-6 cells and primary human osteoblasts. Reversely, Lnc
EPIC1 silencing by targeted siRNA potentiated Dex-induced cytotoxicity. Myc is
the target of Lnc-EPIC1 in osteoblasts. Exogenous overexpression of Myc protected
OB-6 cells from Dex. Conversely, Myc knockout by CRISPR-Cas-9 method abolished
Lnc-EPIC1-induced OB-6 cytoprotection against Dex. Together, Lnc-EPIC1 expression
protects human osteoblasts from Dex possible via regulation of Myc.
PMID- 29959920
TI - Inhibition of eukaryotic translation initiation factor 4E is effective against
chemo-resistance in colon and cervical cancer.
AB - Although cancer patients initially respond well to chemotherapy, they eventually
develop resistance and relapse. In this work, we demonstrate that eIF4E-targeting
therapy is a potential sensitizing strategy for overcoming chemoresistance and
progression in cancer. We show that ribavirin, an anti-viral drug and
pharmacological eIF4E inhibitor, effectively inhibits proliferation and decreases
viability of paclitaxel-resistant cervical cancer and 5-FU-resistant colon cancer
cells while is less toxic to human fibroblast cells. Importantly, oral
administration of ribavirin significantly inhibits paclitaxel-resistant colon and
5-FU-resistant cervical cancer growth in xenograft mouse cancer model without
causing significant toxicity in mice. Consistently, combination of ribavirin with
paclitaxel or 5-FU sensitizes colon and cervical cancer cells to chemotherapeutic
agents treatment in vitro and in vivo. We further confirm that the mechanism of
the action of ribavirin in chemoresistant cancer cells is through suppressing
eIF4E function. In addition, specific eIF4E knockdown via two independent siRNA
mimics the effects of ribavirin in chemoresistant colon and cervical cancer
cells. Cell cycle analysis indicate that ribavirin enhances the anti
proliferative effect of 5-FU by additionally arresting cells at G2/M phase via
increasing cyclin B1, p-histone H3(Ser10) and Mad2 levels. Our work demonstrates
that eIF4E inhibition using inhibitor or siRNA, either as single agent or in
combination, could sensitize chemoresistant cancer cells to paclitaxel or 5-FU
treatment and thereby improving the efficacy of chemodrug. Our findings
demonstrate the therapeutic value of inhibiting eIF4E, particularly in
chemoresistant cancers. Our findings also suggest ribavirin as a promising
sensitizing drug for cancer treatment.
PMID- 29959921
TI - Induction of pigmentation by a small molecule tyrosine kinase inhibitor
nilotinib.
AB - Skin color is determined by the melanin pigments that are produced in melanocytes
then transferred to surrounding keratinocytes. Despite the growing number of
commercial products claiming the pigmentation-regulatory effects, there is still
a demand for the development of new materials that are safe and more efficacious.
We tried to screen the pigmentation-regulatory materials using a commercially
available drugs, and found that nilotinib could induce pigmentation in melanoma
cells. When HM3KO melanoma cells were treated with nilotinib, melanin content was
increased together with increase of tyrosinase activity. Nilotinib increased the
expression of pigmentation-related genes such as MITF, tyrosinase and TRP1.
Consistent with these results, the protein level for MITF, tyrosinase, and TRP1
was significantly increased by nilotinib. To delineate the action mechanism of
nilotinib, we investigated the effects of nilotinib on intracellular signaling.
As a result, nilotinib decreased the phosphorylation of AKT, while increased the
phosphorylation of CREB. The pretreatment of PKA inhibitor H89 markedly blocked
the nilotinib-induced phosphorylation of CREB. In accordance with, pretreatment
of H89 significantly inhibited the nilotinib-induced pigmentation, indicating
that nilotinib induces pigmentation via the activation of PKA signaling.
Together, our data suggest that nilotinib can be developed for the treatment of
hypopigmentary disorder such as vitiligo.
PMID- 29959922
TI - Circular RNA HIPK3 regulates human lens epithelial cells proliferation and
apoptosis by targeting the miR-193a/CRYAA axis.
AB - Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated from back
splicing. Accumulating evidence has demonstrated their vital regulation in
several biological processes and ocular diseases. However, the role of circRNAs
in age-related cataract (ARC), the leading cause of visual impairment worldwide,
is still unknown. CircRNA sequencing reveals that 101 circRNAs are differentially
expressed between the capsules of transparent and ARC lenses, including 75 down
regulated circRNAs and 26 up-regulated circRNAs transcripts. Eight of 10
differentially expressed circRNAs are further verified by quantitative RT-PCRs.
One highly conserved circRNA, circHIPK3, is significantly down-regulated in all
cortical, nuclear and posterior subcapsular subtypes of ARC. The silencing of
circHIPK3, but not HIPK3 mRNA, significantly accelerates apoptosis development
upon oxidative stress and decreases cell viability and proliferation in primary
cultured human lens epithelial cells (HLECs). The expression of alpha-SMA and
vimentin was downregulated, while the expression of E-cadherin and ZO-1was
upregulated, suggesting the repression of epithelial-mesenchymal transition after
circHIPK3 knockdown. CircHIPK3 silencing increases miR-193a expression. miR-193a
regulates CRYAA expression by targeting the binding site within the 3'UTR.
Moreover, miR-193a decreases the viability and proliferation, and increases the
apoptosis of HLECs upon oxidative stress. This study suggests that circRNAs are
the potential regulators in cataractogenesis. CircHIPK3 regulates HLECs function
through miR-193a-mediated CRYAA expression. This finding would provide a novel
insight into the pathogenesis of ARC.
PMID- 29959923
TI - Functional Genomics via CRISPR-Cas.
AB - RNA-guided CRISPR (clustered regularly interspaced short palindromic repeat)
associated Cas proteins have recently emerged as versatile tools to investigate
and engineer the genome. The programmability of CRISPR-Cas has proven especially
useful for probing genomic function in high-throughput. Facile single-guide RNA
library synthesis allows CRISPR-Cas screening to rapidly investigate the
functional consequences of genomic, transcriptomic, and epigenomic perturbations.
Furthermore, by combining CRISPR-Cas perturbations with downstream single-cell
analyses (flow cytometry, expression profiling, etc.), forward screens can
generate robust data sets linking genotypes to complex cellular phenotypes. In
the following review, we highlight recent advances in CRISPR-Cas genomic
screening while outlining protocols and pitfalls associated with screen
implementation. Finally, we describe current challenges limiting the utility of
CRISPR-Cas screening as well as future research needed to resolve these
impediments. As CRISPR-Cas technologies develop, so too will their clinical
applications. Looking ahead, patient centric functional screening in primary
cells will likely play a greater role in disease management and therapeutic
development.
PMID- 29959924
TI - Subunit Exchange in Protein Complexes.
AB - Over the past 50 years, protein complexes have been studied with techniques such
as X-ray crystallography and electron microscopy, generating images which
although detailed are static and homogeneous. More recently, limited application
of in vivo fluorescence and other techniques has revealed that many complexes
previously thought stable and compositionally uniform are dynamically variable,
continually exchanging components with a freely circulating pool of "spares."
Here, we consider the purpose and prevalence of protein exchange, first reviewing
the ongoing story of exchange in the bacterial flagella motor, before surveying
reports of exchange in complexes across all domains of life, together
highlighting great diversity in timescales and functions. Finally, we put this in
the context of high-throughput proteomic studies which hint that exchange might
be the norm, rather than an exception.
PMID- 29959926
TI - Impact of simulated micro-scotomas on reading performance in central and
peripheral retina.
AB - Observers with central field loss typically fixate within a non-foveal region
called the preferred retinal locus, which can include localized sensitivity
losses, or micro-scotomas (Krishnan and Bedell, 2018). In this study, we
simulated micro-scotomas at the fovea and in the peripheral retina to assess
their impact on reading speed. Ten younger (<36 years old) and 8 older (>50 years
old) naive observers with normal vision monocularly read high and/or low contrast
sentences, presented at or above the critical print size for young observers at
the fovea and at 5 and 10 deg in the inferior visual field. Reading material
comprised MNREAD sentences and sentences taken from novels that were presented in
rapid serial visual presentation (RSVP) format. Randomly distributed 13 * 13 arc
min blocks corresponding to 0-78% of the text area (corresponding to ~0-17 micro
scotomas/deg2) were set to the background luminance to simulate micro-scotomas. A
staircase algorithm estimated maximum reading speed from the threshold exposure
duration for each combination of retinal eccentricity, contrast and micro-scotoma
density in both age groups. Log10(RSVP reading speed) decreased significantly
with simulated micro-scotoma density and eccentricity. Across conditions, reading
speed was slower with low-compared to high-contrast text and was faster in
younger than older normal observers. For a given eccentricity and contrast, a
higher density of random element losses maximally affected older observers with
normal vision. These outcomes may explain some of the reading deficits observed
in older observers with central field loss.
PMID- 29959925
TI - Revisit of Reconstituted 30-nm Nucleosome Arrays Reveals an Ensemble of Dynamic
Structures.
AB - It has long been suggested that chromatin may form a fiber with a diameter of ~30
nm that suppresses transcription. Despite nearly four decades of study, the
structural nature of the 30-nm chromatin fiber and conclusive evidence of its
existence in vivo remain elusive. The key support for the existence of specific
30-nm chromatin fiber structures is based on the determination of the structures
of reconstituted nucleosome arrays using X-ray crystallography and single
particle cryo-electron microscopy coupled with glutaraldehyde chemical cross
linking. Here we report the characterization of these nucleosome arrays in
solution using analytical ultracentrifugation, NMR, and small-angle X-ray
scattering. We found that the physical properties of these nucleosome arrays in
solution are not consistent with formation of just a few discrete structures of
nucleosome arrays. In addition, we obtained a crystal of the nucleosome in
complex with the globular domain of linker histone H5 that shows a new form of
nucleosome packing and suggests a plausible alternative compact conformation for
nucleosome arrays. Taken together, our results challenge the key evidence for the
existence of a limited number of structures of reconstituted nucleosome arrays in
solution by revealing that the reconstituted nucleosome arrays are actually best
described as an ensemble of various conformations with a zigzagged arrangement of
nucleosomes. Our finding has implications for understanding the structure and
function of chromatin in vivo.
PMID- 29959927
TI - Quantification of blood flow in the superior ophthalmic vein using phase contrast
magnetic resonance imaging.
AB - Phase contrast magnetic resonance imaging (PC MRI), a validated, non-invasive
technique for measuring intracranial blood and cerebrospinal flows, has been
recently applied to studies of blood flow of the ophthalmic artery (OA). This
study evaluated PC-MRI's ability to quantify blood flow in the superior
ophthalmic vein (SOV). We analyzed with 3 T PC MRI the blood flow in the SOV in
11 healthy subjects and, for comparison purpose, in the OA. Segmentation software
was used to analyze the PC images and quantify the variation in blood flow over
the cardiac cycle in each of the vessels. The anatomy of the orbital veins was
also assessed. We were able to measure the blood flow in 19 SOV; the mean +/-
standard deviation (SD) SOV flow was 9.13 +/- 7.10 mL/min with a mean +/- SD
variation of flow during cardiac cycle of 8.45 +/- 4.90 mL/min. The mean +/- SD
flow in the OA was 12.83 +/- 8.36 mL/min. The SOV was constantly present, with a
mean cross-sectional area of 2.43 mm2. A medium and an inferior ophthalmic veins
were found in 5 and 3 orbits, respectively. In conclusion, PC MRI is able to
measure SOV as well as OA flows. To the best of our knowledge, the present study
is the first to provide quantitative SOV blood flow values using PC MRI.
Investigations of hydrocephalus, intracranial hypertension and even glaucoma
might be facilitated by the application of this quantitative imaging modality.
PMID- 29959928
TI - A new multichannel method quantitating TUNEL in detached photoreceptor nuclei.
AB - Nuclear co-localization labels are critical to ocular research. Among these, the
TUNEL assay has been established as a gold standard of cell death and apoptosis.
While several validated computer-based methods exist to quantitate these markers,
including ImageJ Retina Analysis (RA) Toolkit and ImagePro, none verify the count
with the nuclear counter stain to confirm nuclear co-localization. We established
a new ImageJ-based automated multichannel thresholding (MCT) method to quantitate
nuclear co-localized labeling. The MCT method was validated by comparing it with
the two published TUNEL analysis in TUNEL-positive photoreceptors in an
experimental retinal detachment (RD) model. RDs were induced in murine eyes and
cross-sectional images of TUNEL and DAPI counter stain were obtained. Images were
classified as "typical" or high density "hotspot" TUNEL regions (n = 10/group).
Images were analyzed and compared between the MCT method and the published
techniques including both "standard" and "high" settings of the RA Toolkit for
detecting lower or higher TUNEL densities, respectively. Additional testing of
the MCT method with built-in ImageJ thresholding algorithms was performed to
produce fully automated measurements. All images were compared with Bland-Altman
mean difference plots to assess the difference in counts and linear regression
plots to assess correlation. Comparison between the MCT method and the ImagePro
method were found to be well correlated (typical: R2 = 0.8972, hotspot: R2 =
0.9000) with minor to non-significant differences. The RA Toolkit settings were
found to be mostly well correlated as well (standard/typical: R2 = 0.8036,
standard/hotspot: R2 = 0.4309, high/typical: R2 = 0.7895, high/hotspot: R2 =
0.8738) but were often found to have significantly higher counts than the MCT. In
conclusion, the MCT method compared favorably with validated computer-based
methods of nuclear marker immunofluorescence quantitation and avoids staining
artifacts through the incorporation of the nuclear counter stain to confirm
positive cells.
PMID- 29959929
TI - A randomized controlled trial to determine whether a video presentation improves
informed consent for hysterectomy.
AB - BACKGROUND: Informed consent is an integral part of the preoperative counseling
process. It is important that we know the best way to relay this information to
patients undergoing surgery, specifically, hysterectomy. OBJECTIVE: We sought to
determine whether supplementing normal physician counseling with a video
presentation improves patient comprehension during the informed consent process
for hysterectomy. STUDY DESIGN: In a randomized, mixed factorial controlled
trial, standard physician counseling (control arm) was compared to physician
counseling plus video presentation (video arm) during the prehysterectomy
informed consent process. Primary outcome was improvement in patient
comprehension measured by assessments at baseline, postcounseling, day of
surgery, and postsurgery. Patient satisfaction was measured by a validated
questionnaire. Audiotaped patient-physician interactions were analyzed to
determine time spent counseling, number of patient questions, and whether
standard counseling included 11 predetermined critical components included in the
video. A sample size of 60 per group (N = 120) was planned to compare both
groups. RESULTS: From May 2014 through June 2015, 120 patients were enrolled and
116 randomized: 59 to the video arm and 57 to the control arm. All
characteristics were similar between groups. Video arm subjects demonstrated
greater improvement in comprehension scores in both postcounseling (9.9%
improvement; 95% confidence interval, 4.2-15.7%; P = .0009) and day-of-surgery
questionnaires (7.2% improvement; 95% confidence interval, 0.96-13.4%; P = .02).
Scores 4-6 weeks after surgery returned to baseline for both groups. Control
subjects were less likely to be counseled about risk of thrombosis (P < .0001),
colostomy (P < .0001), further medical/surgical therapy (P = .002), hormone
replacement therapy (P < .0001), or postoperative expectations (P < .0001).
Physicians spent more time counseling patients who did not watch the video (8 vs
12 minutes, P = .003) but number of questions asked by patients in each group was
similar. CONCLUSION: Enhancing prehysterectomy counseling with a video improves
patient comprehension through day of surgery, increases thoroughness of
counseling, and reduces physician time.
PMID- 29959931
TI - Uterine weight and complications after abdominal, laparoscopic, and vaginal
hysterectomy.
AB - BACKGROUND: Although uterine size has been a previously cited barrier to
minimally invasive hysterectomy, experienced gynecologic surgeons have been able
to demonstrate that laparoscopic and vaginal hysterectomy is feasible with
increasingly large uteri. By demonstrating that minimally invasive hysterectomy
continues to have superior outcomes even with increased uterine weights,
opportunity exists to meaningfully decrease morbidity, mortality, and cost
associated with abdominal hysterectomy. OBJECTIVE: We sought to determine if
there is an association between uterine weight and posthysterectomy complications
and if differences in that association exist across vaginal, laparoscopic, and
abdominal approaches. STUDY DESIGN: We conducted a cohort study of prospectively
collected quality improvement data from the American College of Surgeons National
Surgical Quality Improvement Program database, composed of patient information
and 30-day postoperative outcomes from >500 hospitals across the United States
and targeted data files, which includes additional data on procedure-specific
risk factors and outcomes in >100 of those participating hospitals. We analyzed
patients undergoing hysterectomy for benign conditions from 2014 through 2015,
identified by Current Procedural Terminology code. We excluded patients who had
cancer, surgery by a nongynecology specialty, or missing uterine weight. Patients
were compared with respect to 30-day postoperative complications and uterine
weight, stratified by surgical approach. Bivariable tests and multivariable
logistic regression were used for analysis. RESULTS: In all, 27,167 patients were
analyzed. After adjusting for potential confounders, including medical and
surgical variables, women with 500-g uteri were >30% more likely to have
complications compared to women with uteri <=100 g (adjusted odds ratio, 1.34;
95% confidence interval, 1.17-1.54; P < .0001), women with 750-g uteri were
nearly 60% as likely (adjusted odds ratio, 1.58; 95% confidence interval, 1.37
1.82; P < .0001), and women with uteri >=1000 g were >80% more likely (adjusted
odds ratio, 1.85; 95% confidence interval, 1.55-2.21; P < .0001). The incidence
of 30-day postsurgical complications was nearly double in the abdominal
hysterectomy group (15%) compared to the laparoscopic group (8%). Additionally,
for each stratum of uterine weight, abdominal hysterectomy had significantly
higher odds of any complication compared to laparoscopic hysterectomy, even after
adjusting for potential demographic, medical, and surgical confounders. For uteri
<250 g, abdominal hysterectomy had twice the odds of any complication, compared
to laparoscopic hysterectomy (adjusted odds ratio, 2.05; 95% confidence interval,
1.80-2.33), and among women with uteri between 250-500 g, abdominal hysterectomy
was associated with an almost 80% increase in odds of any complication (adjusted
odds ratio, 1.76; 95% confidence interval, 1.41-2.19). Even among women with
uteri >500 g, abdominal hysterectomy was still associated with a >30% increased
odds of any complication, compared to laparoscopic hysterectomy (adjusted odds
ratio, 1.35; 95% confidence interval, 1.07-1.71). CONCLUSION: We found that while
uterine weight was an independent risk factor for posthysterectomy complications,
abdominal hysterectomy had higher odds of any complication, compared to
laparoscopic hysterectomy, even for markedly enlarged uteri. Our study suggests
that uterine weight alone is not an appropriate indication for abdominal
hysterectomy. We also identified that it is safe to perform larger hysterectomies
laparoscopically. Patients may benefit from referral to experienced surgeons who
are able to offer laparoscopic hysterectomy even for markedly enlarged uteri.
PMID- 29959930
TI - Physical examination techniques for the assessment of pelvic floor myofascial
pain: a systematic review.
AB - BACKGROUND: Myofascial pain is characterized by the presence of trigger points,
tenderness to palpation, and local or referred pain, and commonly involves the
pelvic floor muscles in men and women. Pelvic floor myofascial pain in the
absence of local or referred pain has also been observed in patients with lower
urinary tract symptoms, and we have found that many patients report an
improvement in these symptoms after receiving myofascial-targeted pelvic floor
physical therapy. OBJECTIVE: We sought to systematically review the literature
for examination techniques used to assess pelvic floor myofascial pain in women.
STUDY DESIGN: We performed a systematic literature search using strategies for
the concepts of pelvic floor disorders, myofascial pain, and diagnosis in Ovid
MEDLINE 1946-, Embase 1947-, Scopus 1960-, Cochrane Central Register of
Controlled Trials, Database of Abstracts of Reviews of Effects, and Cochrane
Database of Systematic Reviews. Articles were screened by 3 authors and included
if they contained a description of a pelvic myofascial physical examination.
RESULTS: In all, 55 studies met our inclusion criteria. Overall, examination
components varied significantly among the included studies and were frequently
undefined. A consensus examination guideline was developed based on the available
data and includes use of a single digit (62%, 34/55) to perform transvaginal
palpation (75%, 41/55) of the levator ani (87%, 48/55) and obturator internus
(45%, 25/55) muscles with a patient-reported scale to assess the level of pain to
palpation (51%, 28/55). CONCLUSION: Physical examination methods to evaluate
pelvic musculature for presence of myofascial pain varied significantly and were
often undefined. Given the known role of pelvic floor myofascial pain in chronic
pelvic pain and link between pelvic floor myofascial pain and lower urinary tract
symptoms, physicians should be trained to evaluate for pelvic floor myofascial
pain as part of their physical examination in patients presenting with these
symptoms. Therefore, the development and standardization of a reliable and
reproducible examination is needed.
PMID- 29959932
TI - Changes in the burnout profile of chairs of academic departments of obstetrics
and gynecology over the past 15 years.
AB - BACKGROUND: While many studies have documented the high prevalence of burnout in
practicing physicians and medical trainees, fewer reports describe burnout in
academic leaders. In 2002, we observed a moderate-high to high level of burnout
in 41.4% of chairs of academic departments of obstetrics and gynecology.
OBJECTIVE: The purpose of this study was to identify trends in burnout and
associated factors in today's obstetrics and gynecology chairs as they face
complex changes to the current health care environment. STUDY DESIGN: This was a
cross-sectional study. A survey was developed based on the questionnaire used in
our first investigation and sent electronically to all members of the Council of
University Chairs of Obstetrics and Gynecology. Burnout was measured using an
abbreviated Maslach Burnout Inventory-Human Sciences Survey. In addition to
demographic data, we assessed perceived stressors, job satisfaction,
spousal/partner support, self-efficacy, depression, suicidal ideation, and stress
management. RESULTS: The response rate was 60% (84/139). Almost 30% of chairs
were women, increased from 7.6% in 2002. Hospital and department budget deficits
and loss of key faculty remain major stressors noted by participants. The Maslach
Burnout Inventory results have changed dramatically over the past 15 years.
Today's chairs demonstrated less burnout but with an "ineffective" profile.
Subscale scores for emotional exhaustion and depersonalization were reduced but
>50% reported low personal accomplishment. Spousal support remained important in
preventing burnout. CONCLUSION: Chairs of academic departments of obstetrics and
gynecology continue to face significant job-related stress. Burnout has
decreased; however, personal accomplishment scores have also declined most likely
due to administrative factors that are beyond the chairs' perceived control.
PMID- 29959934
TI - Correlation Between Pharyngeal Residue and Aspiration In Fiberoptic Endoscopic
Evaluation of Swallowing - An Observational Study.
AB - OBJECTIVES: To examine the correlation between pharyngeal residue severity and
clearance to penetration-aspiration on FEES. DESIGN: Retrospective cohort.
SETTING: Kaplan Medical Center dysphagia clinic. PARTICIPANTS: 110 patients
visiting a dysphagia clinic between 2014-2016 undergoing FEES. INTERVENTIONS:
FEES were scored for penetration-aspiration with the penetration-aspiration scale
(PAS), for residue severity using the Yale Pharyngeal Residue Severity Rating
Scale, YPR-SRS. The numbers of swallows required to clear the pharynx were
recorded. The first and the worst bolus challenge for each consistency (liquid,
puree and solid) were analyzed. MAIN OUTCOME MEASURES: YPR-SRS and number of
clearing swallows were correlated with the PAS of the same bolus challenge.
RESULTS: The study population's mean age was 67+/-13.4 years; 54% were males
(n=58). A significant correlation was found between the YPR-SRS and the PAS for
all consistencies tested, in each anatomical site (vallecula or pyriform sinus)
and for both the first and worst bolus challenge (p<0.001 for all). The
correlation of residue with aspiration was stronger when vallecula and pyriform
sinuses scores were summated (Pearson's correlation coefficient=0.573/0.631/0.446
for liquid/puree/solid for worst bolus challenge). Incorporating the number of
clearing swallows to the YPR-SRS strengthened the correlation with PAS.
CONCLUSIONS: Residue severity and clearance correlate with penetration/aspiration
on FEES. The YPR-SRS can be applied to standardize description of residue in FEES
and to aid in dysphagia evaluation.
PMID- 29959935
TI - Reply by Authors.
PMID- 29959936
TI - Editorial Comment.
PMID- 29959933
TI - A cautionary response to SMFM statement: pharmacological treatment of gestational
diabetes.
AB - Use of oral agents to treat gestational diabetes mellitus remains controversial.
Recent recommendations from the Society for Maternal-Fetal Medicine assert that
metformin may be a safe first-line alternative to insulin for gestational
diabetes mellitus treatment and preferable to glyburide. However, several issues
should give pause to the widespread adoption of metformin use during pregnancy.
Fetal concentrations of metformin are equal to maternal, and metformin can
inhibit growth, suppress mitochondrial respiration, have epigenetic modifications
on gene expression, mimic fetal nutrient restriction, and alter postnatal
gluconeogenic responses. Because both the placenta and fetus express metformin
transporters and exhibit high mitochondrial activity, these properties raise
important questions about developmental programming of metabolic disease in
offspring. Animal studies have demonstrated that prenatal metformin exposure
results in adverse long-term outcomes on body weight and metabolism. Two recent
clinical randomized controlled trials in women with gestational diabetes mellitus
or polycystic ovary syndrome provide evidence that metformin exposure in utero
may produce a metabolic phenotype that increases childhood weight or obesity.
These developmental programming effects challenge the conclusion that metformin
is equivalent to insulin. Although the Society for Maternal-Fetal Medicine
statement endorsed metformin over glyburide if oral agents are used, there are
few studies directly comparing the 2 agents and it is not clear that metformin
alone is superior to glyburide. Moreover, it should be noted that prior clinical
studies have dosed glyburide in a manner inconsistent with its pharmacokinetic
properties, resulting in poor glycemic control and high rates of maternal
hypoglycemia. We concur with the American Diabetes Association and American
Congress of Obstetricians and Gynecologists, which recommend insulin as the
preferred agent, but we believe that it is premature to embrace metformin as
equivalent to insulin or superior to glyburide. Due to the uncertainty of the
long-term metabolic risks of either metformin or glyburide, we call for carefully
controlled studies that optimize oral medication dosing according to their
pharmacodynamic and pharmacokinetic properties in pregnancy, appropriately target
medications based on individual patterns of hyperglycemia, and follow the
offspring long-term for metabolic risk.
PMID- 29959938
TI - Editorial Comment.
PMID- 29959937
TI - Editorial Comment.
PMID- 29959939
TI - Reply by Authors.
PMID- 29959940
TI - Higher Use of Surgery Confers Superior Survival in Stage I Non-Small Cell Lung
Cancer.
AB - BACKGROUND: Lobar resection is the gold standard therapy for medically fit
patients with stage I non-small cell lung cancer (NSCLC). However, considerable
variability exists in the use of surgical therapy. This study tested the
hypothesis that center-based variation in the use of surgical therapy affects
survival in NSCLC. METHODS: We queried the National Cancer Database for patients
with stage I NSCLC. Mixed-effects multivariable models were developed to
establish the per-center adjusted rate of surgical therapy. Patients were
stratified into quartiles based on the treating center's adjusted rate of
surgical therapy. Survival was estimated and then tested by using Kaplan-Meier
and the log-rank test. Multivariable Cox proportional hazard models were
developed to estimate the effect of rate of surgical therapy on overall survival.
RESULTS: A total of 139,802 patients met the criteria. There was wide variation
in the per-center rate of surgical resection in the highest (80.8%) versus lowest
(41.4%, p < 0.001) quartile. Across cohorts, patients were similar in age (mean
68.8 years in the highest quartile versus 69.7 in the lowest quartile) and
Charlson-Deyo Score of 2 or greater (15.1% in the highest quartile versus 14.4%
in the lowest quartile). Five-year survival was higher for patients treated at
high-use centers (52.7% versus 36.7%, p < 0.001). After adjustment, an adjusted
rate of surgical therapy in the lowest 25th percentile was associated with lower
survival (adjusted hazard ratio 1.40, 95% confidence interval: 1.37 to 1.40, p <
0.001). CONCLUSIONS: Treatment at a center with a higher rate of surgical therapy
confers a considerable survival advantage, even after adjustment for hospital
volume, surgical approach, and other confounders. Targeted efforts to improve
adherence to guidelines about provision of surgical therapy in early-stage NSCLC
may represent a meaningful opportunity to improve outcomes.
PMID- 29959941
TI - Frailty Characteristics Predict Respiratory Failure in Patients Undergoing
Tracheobronchoplasty.
AB - BACKGROUND: Respiratory complications are the leading cause of morbidity in
patients undergoing tracheobronchoplasty, yet risk stratification systems on this
population are insufficient. We investigated the association between frailty and
risk of major respiratory complications after tracheobronchoplasty. METHODS: A
retrospective review was made of 161 consecutive tracheobronchoplasties (October
2002 to September 2016). A frailty index was developed by the deficit
accumulation approach comprising 26 multidomain preoperative variables. The main
outcome was a composite endpoint of major respiratory complications within 30
days of surgery. Odds ratio (OR) and 95% confidence interval (CI) were estimated
using logistic regression. RESULTS: The cohort consisted of 103 women (64%),
median age of 58 years (interquartile range, 51 to 66) and median FI of 0.25
(interquartile range, 0.1 to 0.3). Forty-eight patients (30%) had respiratory
complications, the most common being respiratory failure (n = 27, 16.8%) and
pneumonia (n = 25, 15.5%). Severe frailty (frailty index >=0.33) was strongly
associated with major respiratory complications (73.8% versus 2.5%; OR 58.8, 95%
CI: 9.6 to 358.3). The association with severe frailty appeared stronger for
respiratory failure (47.6% versus 2.5%; OR 30, 95% CI: 4.7 to 189.9) than for
pneumonia (40.5% versus 0%; OR 35.2. 95% CI: 2.0 to 599.8). Further adjustment
for intraoperative crystalloid volume or forced expiratory volume in 1 second
moderately attenuated the association between frailty with major respiratory
complications (OR 17.4. 95% CI: 2.0 to 150.8), respiratory failure (OR 13.1, 95%
CI: 1.7 to 95.8), and pneumonia (OR 20.1, 95% CI: 1.1 to 341.8). CONCLUSIONS:
Frailty, as indicated by frailty index, was associated with major respiratory
complications, particularly respiratory failure after tracheobronchoplasty.
Preoperative identification of frailty may help guide decision making for
patients considering this effective, although arduous procedure.
PMID- 29959942
TI - Partial Hammock Valve: Surgical Repair and Long-Term Follow-Up in 23 Patients.
AB - BACKGROUND: In 2006, we reported a "forme frustree" of hammock valve involving
the posterior mitral leaflet resulting in restricted leaflet motion and mitral
regurgitation. The purpose of this retrospective report is to describe the
surgical techniques and long-term outcome of 23 patients with partial hammock
valve who underwent successful repaired over a 22-year period (1995 to 2017).
METHODS: Partial hammock valve is defined as anomalous papillary muscles that
have hypertrophied and fused together. There are three or four papillary muscles
implanted high on the posterior wall, forming a palisade under the posterior
leaflet. Twenty-three patients were operated on, 19 adults and 4 children. In all
but 3 patients, repair consisted of posterior leaflet enlargement of the P2 and
P3 segments with a semilunar patch of bovine pericardium. The fused papillary
muscles were split longitudinally, and some secondary chordae were cut. All adult
patients received a prosthetic ring. RESULTS: A satisfactory repair was achieved
in all patients. Mean age at the time of operation was 62 +/- 11 years (range, 6
days to 79 years). Hospital mortality occurred in 1 patient (1 of 23; 4.3%). Mean
follow-up was 7 years (range, 1 to 22). Actuarial survival rate at 7 years was
70%. At last echocardiogram, all survivors were free from mitral regurgitation
grade II or higher. There was no reoperation. CONCLUSIONS: Partial hammock valve
is a rare congenital anomaly resulting in mitral regurgitation. Patch enlargement
of the posterior leaflet achieves long-term repair. It is safe and reliable.
PMID- 29959943
TI - Meta-Analysis of Peripheral or Central ECMO in Postcardiotomy and Non
Postcardiotomy Shock.
AB - BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO)
application in post-cardiotomy shock (PCS) and non-PCS is increasing. VA-ECMO
plays a critical role in the management of these patients, yet may be associated
with serious complications. METHODS: A systematic review of all available reports
in the literature of patients receiving VA-ECMO, either directly or indirectly
comparing central cannulation (right atrial to ascending aorta) versus peripheral
cannulation (femoral vein to femoral artery or axillary artery) were analyzed.
The primary endpoint was survival. Cerebrovascular events, limb complications,
bleeding requiring reoperation, sepsis, continuous veno-venous hemofiltration,
and transfusions, were also assessed in both groups. RESULTS: Seventeen
retrospective case series clearly describing the VA-ECMO access and including
1,691 patients with PC- and non-PCS were found. The peripheral approach was more
commonly used (980 patients, 57.9%) than the central one. There was no difference
in the analysis between the two techniques regarding all-cause mortality RR (Risk
Ratio) 95 CIs (Confidence Intervals): 1.00 (0.94-1.08) I2=0%, P=0.92. No
statistical differences were found between peripheral and central VA-ECMO with
regards to cerebrovascular events, limb complications, or sepsis rates.
Peripheral cannulation, was associated with a significant reduction in the risk
of bleeding (p=0.02), continuous veno-venous hemofiltration (p=0.03), transfusion
of red blood cells units (p<0.00001), fresh frozen plasma units (p=0.0002) and
platelets units (p<0.00001). CONCLUSIONS: Peripheral and central VA-ECMO
configurations showed comparable in-hospital survival in PCS and non-PCS. The
risk of bleeding, continuous veno-venous hemofiltration and blood product
transfusion was significantly lower with the peripheral cannulation strategy.
PMID- 29959945
TI - Improving pharmacological treatment in brain and mental health disorders: the
need for gender and sex analyses.
PMID- 29959944
TI - Residual Arch Tears and Major Adverse Events After Acute DeBakey Type I Aortic
Dissection Repair.
AB - BACKGROUND: Tear-oriented surgical procedure is considered a standard treatment
for acute DeBakey type I aortic dissection (AIAD). However, long-term surgical
outcomes, including aortic growth and rate of major adverse aortic events
(MAAEs), have yet to be clarified. METHODS: Of the 274 patients who underwent
surgical repair for AIAD between 2009 and 2016, 105 patients with both
predischarge and follow-up computed tomographic scans were enrolled. The surgical
extent was determined by primary entry tear location. We measured aortic
diameters (pulmonary artery bifurcation, maximum diameter of the descending
thoracic aorta [maxDTA], and celiac axis) and compared MAAEs (aorta growth rate
>= 5 mm/year or maxDTA >= 55 mm according to surgical extent). RESULTS: Twenty
nine patients underwent total arch replacement (TAR); 76 underwent non-TAR. In
the non-TAR group, patients with or without residual tears in the arch vessels
were classified as having complete arch repair (non-TAR-CAR, n = 52) or
incomplete arch repair (non-TAR-IAR, n = 24). Considerable differences were found
in the aortic growth rate between the TAR and non-TAR groups and the non-TAR-CAR
and non-TAR-IAR groups. Freedom from MAAEs at 5 years was considerably higher in
the non-TAR-CAR group than in the non-TAR-IAR group (84.5% versus 31.1%).
However, no differences were observed in the aortic growth rate and freedom from
MAAEs between the TAR and non-TAR-CAR groups. CONCLUSIONS: Classic tear-oriented
surgical procedure is insufficient for optimal long-term surgical outcomes,
mainly regarding aortic dilation. CAR without residual arch vessel tears leads to
favorable aortic remodeling in the residual DTA and prevents MAAEs after AIAD
repair.
PMID- 29959946
TI - Effects of population- and seed bank size fluctuations on neutral evolution and
efficacy of natural selection.
AB - Population genetics models typically consider a fixed population size and a
unique selection coefficient. However, population dynamics inherently generate
fluctuations in numbers of individuals and selection acts on various components
of the individuals' fitness. In plant species with seed banks, the size of both
the above- and below-ground compartments induce fluctuations depending on seed
production and the state of the seed bank. We investigate if this fluctuation has
consequences on (1) the rate of genetic drift, and (2) the efficacy of selection.
We consider four variants of two-allele Moran-type models defined by combinations
of presence and absence of fluctuations in the population size in above-ground
and seed bank compartments. Time scale analysis and dimension reduction methods
allow us to reduce the corresponding Fokker-Planck equations to one-dimensional
diffusion approximations of a Moran model. We first show that if the fluctuations
of above-ground population size classically affect the rate of genetic drift,
fluctuations of below-ground population size reduce the diversity storage effect
of the seed bank. Second, we consider that selection can act on four different
components of the plant fitness: plant or seed death rate, seed production or
seed germination. Our striking result is that the efficacy of selection for seed
death rate or germination rate is reduced by fluctuations in the seed bank size,
whereas selection occurring on plant death rate or seed production is not
affected. We derive the expected site-frequency spectrum reflecting this
heterogeneity in selection efficacy between genes underpinning different plant
fitness components. Our results highlight the importance to consider the effect
of ecological noise to predict the impact of seed banks on neutral and selective
evolution.
PMID- 29959947
TI - Contemporary lipidomic analytics: opportunities and pitfalls.
AB - Recent advances in analytical techniques have greatly enhanced the depth of
coverage, however lipidomic studies are still restricted to analysing only a
subset of known lipids. Numerous complementary techniques are used for
investigation of cellular lipidomes, including mass spectrometry (MS), nuclear
magnetic resonance and vibrational spectroscopy. The development in electrospray
ionization (ESI) MS has accelerated lipidomics research in the past two decades
and represents one of the most widely used technique. The versatility of ESI-MS
systems allows development of methods to detect and quantify a large diversity of
lipid species and classes. However, highly targeted and specific approaches can
preclude global analysis of many lipid classes. Indeed, experimental procedures
are generally optimised for the lipid species, or lipid class of interest.
Therefore, careful consideration of experimental procedures is required for
characterisation of biological lipidomes. The current review will describe the
lipidomic approaches for considering tissue lipid physiology. Discussion of the
main sequences in a lipidomics workflow will be presented, including preparation
of samples, accurate quantitation of lipid species and statistical modelling.
PMID- 29959948
TI - Chitins and chitinase activity in airway diseases.
AB - Chitin, one of the most abundant biopolymers on Earth, is bound and degraded by
chitinases, specialized enzymes that are similarly widespread in nature. Chitin
catabolism affects global carbon and nitrogen cycles through a host of diverse
biological processes, but recent work has focused attention on systems of chitin
recognition and degradation conserved in mammals, connecting an ancient pathway
of polysaccharide processing to human diseases influenced by persistent immune
triggering. Here we review current advances in our understanding of how chitin
chitinase interactions affect mucosal immune feedback mechanisms essential to
maintaining homeostasis and organ health.
PMID- 29959949
TI - How to choose biomarkers in view of parameter estimation.
AB - In numerous applications in biophysics, physiology and medicine, the system of
interest is studied by monitoring quantities, called biomarkers, extracted from
measurements. These biomarkers convey some information about relevant hidden
quantities, which can be seen as parameters of an underlying model. In this paper
we propose a strategy to automatically design biomarkers to estimate a given
parameter. Such biomarkers are chosen as the solution of a sparse optimization
problem given a user-supplied dictionary of candidate features. The method is in
particular illustrated with two realistic applications, one in electrophysiology
and the other in hemodynamics. In both cases, our algorithm provides composite
biomarkers which improve the parameter estimation problem.
PMID- 29959950
TI - Serum level of the autophagy biomarker Beclin-1 in patients with diabetic kidney
disease.
AB - : Autophagy is a major cellular clearance mechanism that maintains cellular
survival and homeostasis. Autophagy has a crucial role in the progression of
diabetes and kidney diseases. AIMS: To investigate serum concentrations of Beclin
1, a key regulator of autophagy, in patients with diabetic kidney disease (DKD).
METHODS: The study included 70 patients with type 2 diabetes and DKD (group 1; 35
patients with estimated glomerular filtration rate (eGFR) >= 30 ml/min/1.73 m2
and group 2; 35 patients with eGFR < 30 ml/min/1.73 m2) and 20 age- and sex
matched healthy subjects (group 3). Laboratory work up included; glycated
hemoglobin (HbA1c), serum creatinine, eGFR using modification of diet in renal
disease (MDRD) formula, urine albumin to creatinine ratio (ACR), and serum Beclin
1 measurement. RESULTS: Patients with DKD had significantly lower Beclin-1 levels
(2.38 +/- 1.46 ng/mL) compared to control group (6.03 +/- 1.94 ng/mL; P < 0.001).
Moreover, serum Beclin-1 significantly decreased in group 2 (1.43 +/- 0.83 ng/mL)
compared to group 1 (3.36 +/- 1.30 ng/mL; P < 0.001). In univariate analysis, the
concentration of Beclin-1 correlated well with eGFR (r = 0.64, P < 0.001), ACR (r
= -0.63, P < 0.001), and duration of diabetes (r = -0.43, P < 0.001) but didn't
correlate with HbA1c (r = -0.17, P = 0.15). However, ACR was the only significant
predictor of Beclin-1 level on performing multiple regression analysis (beta =
0.40, P = 0.01). CONCLUSION: Serum level of Beclin-1 is reduced in patients with
DKD. Furthermore, its level is related to the stage of DKD and correlates with
the degree of albuminuria.
PMID- 29959951
TI - A systematic review on economic evaluations of school-based lifestyle
interventions targeting weight-related behaviours among 4-12 year olds: Issues
and ways forward.
AB - Current guidelines for economic evaluations do not provide specific
recommendations for the evaluation of school-based lifestyle interventions. This
study examined and discussed the key aspects in the design of economic
evaluations on school-based interventions targeting weight-related behaviours
among 4-12 year olds. The PubMed and CRD databases (NHS EED) were searched. Grey
literature was identified from reference lists and websites of relevant
organizations. Full economic evaluations on school-based interventions targeting
physical activity, sedentariness, or diet were selected. Key aspects included the
objective, audience, intervention, comparator, population, type of analysis,
perspective, costs, outcomes, and time horizon. Information was also extracted on
measuring and valuing costs and outcomes, linking and extrapolating outcomes, and
the maintenance of intervention effects. The 23 included studies reported on cost
effectiveness (CEAs) (N = 12), cost-utility (CUAs) (N = 9), social cost benefit
(SCBA) (N = 2), and social return on investment (SROI) (N = 1) analysis. The
usual practice comparator was generally not clearly defined. The SROI analysis
was the single study that included outcomes in other persons than the child.
Healthcare costs (N = 14), productivity costs (N = 4), and costs to the household
(N = 3), or education (N = 2) sector were examined. The outcome in trial-based
CEAs consisted of a variety of weight-related measures. Seven distinctive models
were used to extrapolate health and/or productivity costs. To enhance the
usefulness of economic evaluations on school-based lifestyle interventions in
allocating public health budgets, transparent reporting on key aspects,
broadening the scope of economic evaluations, and standardizing the measurement,
valuation, and extrapolation of costs and outcomes should be improved. This study
was conducted in Maastricht, the Netherlands.
PMID- 29959953
TI - The removal of DAA restrictions in Europe - One step closer to eliminating HCV as
a major public health threat.
AB - Of ~10.2 million people with chronic HCV infection in Europe, 6.7 million live in
Eastern Europe, 2.3 million in Western Europe and 1.2 million in Central Europe.
HCV transmission continues to occur in parallel with an increasing HCV-related
liver disease burden, the result of an ageing population infected during peak HCV
epidemics decades earlier. In 2016, the World Health Organization set targets to
eliminate HCV infection as a major public health threat by 2030. Across Europe,
an estimated 36% of those living with chronic HCV infection have been diagnosed
and ~5% have been treated. A major barrier to enhancing HCV treatment uptake has
been restrictions set by payers, including national governments and others, in
response to the initially high list prices of direct-acting antiviral (DAA)
therapies. The aims of this article are to discuss DAA restrictions in Europe,
why DAA restrictions are still in place, what has facilitated the removal of DAA
restrictions, and what challenges remain as we attempt to eliminate HCV as a
major public health threat in the region by 2030.
PMID- 29959952
TI - Less is more: Negative income shock increases immediate preference in cross
commodity discounting and food demand.
AB - Negative income shock, or the rapid reduction in financial stability, has
previously been shown to increase impulsive choice for money and demand for fast
food. The interplay of these conditions for obesity is called reinforcer
pathology. The present work examines the impact of negative income shock on
monetary and fast food discounting using a cross-commodity delay discounting task
and on purchasing of fast food and an alternative commodity. An obese sample (n =
120) was recruited from Amazon Mechanical Turk and assigned to read one of two
narratives: negative income shock (n = 60) or control (n = 60). Participants then
completed both within- and cross-commodity discounting tasks of money and food,
and purchase tasks for fast food and bottled water. The negative income shock
group demonstrated greater impulsive choice across discounting tasks, as well as
higher intensity of demand for fast food but not for a non-caloric control
commodity (bottled water). These results suggest that negative income shock
increases preference for immediate reinforcement regardless of commodity type
(money or fast food), but has specific effects increasing demand for particular
commodities (fast food but not an alternative). In a reinforcer pathology
framework, negative income shock increasing discounting of the future while
increasing demand for fast food specifically represents a high-risk state for
negative health behavior in obesity.
PMID- 29959954
TI - A PCR detection method for discerning Serratia marcescens in extended boar semen.
AB - Serratia marcescens is a bacterial contaminant that can be spermicidal when
present in extended boar semen that is typically stored prior to breeding use at
15 to 18 degrees C for several days. This particular contaminant appears to
originate from carrier boars, where it resides in the preputial cavity, but has
also been shown to then easily contaminate the semen-processing laboratory.
Screening for carrier boars to date has been performed through detection of
S.marcescens in ejaculates using traditional agar plate culture techniques. These
agar growth techniques are labor and time consuming due to the need for sample
degrees titration and temporal growth followed by isolation, leading to delays in
identification. The aim of this study was to develop a rapid, sensitive
traditional PCR technique that can detect the presence of S.marcescens in
extended boar semen. Primers for the detection of S. marcescens 16S rRNA were
designed and specificity tested. After PCR optimization, assay sensitivity was
evaluated using extended boar semen that was inoculated with various
physiological ratios of spermatozoa: S.marcescens (100:1, 50:1, 20:1, 10:1, 8:1,
6:1, 4:1, 2:1. 1:1 and 1:10). Samples, held at 16 degrees C, were tested every
24 h over a 96 h period, with bacterial DNA extraction performed at each time
point using a commercial kit. As a final step, the developed technique was used
to screen random samples of extended boar semen for S. marcescens contamination.
Results showed that this PCR technique had a sensitivity (90%) and specificity
(100%) at detecting S.marcescens in the different inoculated ratios as well as in
random, naturally contaminated samples of extended boar semen. In conclusion,
this study reports a traditional PCR technique that is effective at rapidly and
accurately detecting the presence of S.marcescens in boar extended semen.
PMID- 29959955
TI - Development of a rapid PCR-Nucleic Acid Lateral Flow Immunoassay (PCR-NALFIA)
based on rDNA IGS sequence analysis for the detection of Macrophomina phaseolina
in soil.
AB - The 'Nucleic Acid Lateral Flow Immunoassay' (NALFIA) using a generic 'Lateral
Flow Device' (LFD), combined with PCR employing labelled primers (PCR-NALFIA),
enables to circumvent the use of electrophoresis, making the diagnostic procedure
more rapid and easier. If the specific amplicon is present in the sample, a
coloured band, with an intensity proportional to the amplicon concentration, will
develop on the LFD strip in addition to the control band. Species-specific
primers for M. phaseolina based on the rDNA intergenic spacer (IGS) were
developed and their specificity was checked and confirmed using 20 isolates of M.
phaseolina and other 16 non-target fungi. A DNA extraction protocol based on a
bead-beating technique using silica beads, skimmed milk and PVP was also
developed. The M. phaseolina specific primers MP102F/MP102R, 5' labelled with
biotin and FITC respectively, were used in the PCR-NALFIA assay to identify the
pathogen starting from mycelium or microsclerotia. Microsclerotia of M.
phaseolina (1, 10, 100 and 200) were manipulated under a stereomicroscope and
their DNA was extracted using microsclerotia alone or mixed with different types
of soil. The resulting DNA, used for the PCR-NALFIA assay, provided positive
results for all the samples tested. A semi-quantitative grey-scale reference card
based on the PCR-NALFIA assay using intervals corresponding to microsclerotia
soil number was developed. For this purpose, the normalized pixel grey volumes
obtained after a densitometric analysis of the test line intensity generated by
the LFD dipsticks were used.
PMID- 29959956
TI - A tour of contemporary color vision research.
AB - The study of color vision encompasses many disciplines, including art,
biochemistry, biophysics, brain imaging, cognitive neuroscience, color
preferences, colorimetry, computer modelling, design, electrophysiology, language
and cognition, molecular genetics, neuroscience, physiological optics,
psychophysics and physiological optics. Coupled with the elusive nature of the
subjective experience of color, this wide range of disciplines makes the study of
color as challenging as it is fascinating. This overview of the special issue
Color: Cone Opponency and Beyond outlines the state of the science of color, and
points to some of the many questions that remain to be answered in this exciting
field.
PMID- 29959958
TI - The emerging role of physiologically based pharmacokinetic modelling in solid
drug nanoparticle translation.
AB - The use of solid drug nanoparticles (SDN) has become an established approach to
improve drug delivery, supporting enhancement of oral absorption and long-acting
administration strategies. A broad range of SDNs have been successfully utilised
for multiple products and several development programmes are currently underway
across different therapeutic areas. With some approaches, a large range of
material space is available with diversity in physical characteristics, excipient
choice and pharmacological behaviour. The selection of SDN lead candidates is a
complex process including a broad range of in vitro and in vivo data, and a
better understanding of how physical characteristics relate to performance is
required. Physiologically-based pharmacokinetic (PBPK) modelling is based upon a
comprehensive integration of experimental data into a mathematical description of
drug distribution, allowing simulation of SDN pharmacokinetics that can be
qualified in vivo prior to human prediction. This review aims to provide a
description of how PBPK can find application into the development of SDN.
Integration of predictive PBPK modelling into SDN development allows a better
understanding of the SDN dose-response relationship, supporting a framework for
rational optimisation while reducing the risk of failure in developing safe and
effective nanomedicines.
PMID- 29959957
TI - Chronic stress dysregulates amygdalar output to the prefrontal cortex.
AB - Chronic stress contributes to the neuropathology of mental health disorders,
including those associated with anxiety. The basolateral amygdala (BLA)
coordinates emotional behavioral responses through glutamatergic outputs to
downstream regions such as the prefrontal cortex (PFC), nucleus accumbens core
(NAcc) and bed nucleus of the stria terminalis (BNST). We explored the effects of
chronic stress on BLA outputs to the PFC, NAcc and BNST using slice
electrophysiology combined with optogenetics in two inbred mouse strains with
distinct stress-induced anxiety responses. We found that ten consecutive days of
chronic restraint stress enhanced pre-synaptic glutamate release at BLA-to-PFC
synapses in C57BL/6J mice, but reduced pre-synaptic glutamate release at these
synapses in DBA/2J mice. To assess the behavioral relevance of enhanced glutamate
output at BLA-to-PFC synapses, we approximated the effects of chronic stress on
the BLA-PFC circuit using optogenetics. We found that photostimulation of the BLA
PFC circuit in unstressed C57BL/6J mice produced persistent (i.e., post
stimulation) increased anxiety-like behavior and hyperactivity in the elevated
plus-maze - a profile consistent with prototypical behavioral responses of
stressed C57BL/6J mice. These data demonstrate that chronic stress dysregulates
the BLA-PFC circuit by altering pre-synaptic glutamate release from BLA outputs,
and provide a mechanism by which chronic stress can lead to increased anxiety.
PMID- 29959959
TI - Strategic design of extracellular vesicle drug delivery systems.
AB - Extracellular vesicles (EVs), sub-micron vectors used in intercellular
communication, have demonstrated great promise as natural drug delivery systems.
Recent reports have detailed impressive in vivo results from the administration
of EVs pre-loaded with therapeutic cargo, including small molecules,
nanoparticles, proteins and oligonucleotides. These results have sparked
intensive research interest across a huge range of disease models. There are,
however, enduring limitations that have restricted widespread clinical and
pharmaceutical adoption. In this perspective, we discuss these practical and
biological concerns, critically compare the relative merit of EVs and synthetic
drug delivery systems, and highlight the need for a more comprehensive
understanding of in vivo transport and delivery. Within this framework, we seek
to establish key areas in which EVs can gain a competitive advantage in order to
provide the tangible added value required for widespread translation.
PMID- 29959960
TI - Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and
cooperative gating.
AB - L-type CaV1.2 channels are key regulators of gene expression, cell excitability
and muscle contraction. CaV1.2 channels organize in clusters throughout the
plasma membrane. This channel organization has been suggested to contribute to
the concerted activation of adjacent CaV1.2 channels (e.g. cooperative gating).
Here, we tested the hypothesis that dynamic intracellular and perimembrane
trafficking of CaV1.2 channels is critical for formation and dissolution of
functional channel clusters mediating cooperative gating. We found that CaV1.2
moves in vesicular structures of circular and tubular shape with diverse
intracellular and submembrane trafficking patterns. Both microtubules and actin
filaments are required for dynamic movement of CaV1.2 vesicles. These vesicles
undergo constitutive homotypic fusion and fission events that sustain CaV1.2
clustering, channel activity and cooperative gating. Our study suggests that
CaV1.2 clusters and activity can be modulated by diverse and unique intracellular
and perimembrane vesicular dynamics to fine-tune Ca2+ signals.
PMID- 29959961
TI - Part I: Onychomycosis: Clinical Overview and Diagnosis.
AB - Onychomycosis is a fungal nail infection caused by dermatophytes, non
dermatophytes, and yeast and is the most common nail disorder seen in clinical
practice. It is an important problem, as it may cause local pain, paresthesias,
difficulties performing activities of daily life, and impair social interactions.
In the following continuing medical education manuscript, we review the
epidemiology, risk factors, and clinical presentation of onychomycosis and
demonstrate current and emerging diagnostic strategies.
PMID- 29959962
TI - Part II: Onychomycosis: Treatment and Prevention of Recurrence.
AB - Onychomycosis is a fungal nail infection caused by dermatophytes, non
dermatophytes, and yeast and is the most common nail disorder seen in clinical
practice. It is an important problem, as it may cause local pain, paresthesias,
difficulties performing activities of daily life, and impair social interactions.
The epidemiology, risk factors, and clinical presentation and diagnosis of
onychomycosis were discussed in the first article in this continuing medical
education series. In this article, we review the prognosis and response to
onychomycosis treatment, Food and Drug Administration approved medications for
onychomycosis, as well as, off-label therapies and devices. Methods to prevent
onychomycosis recurrences and emerging therapies are also described.
PMID- 29959963
TI - Purinergic modulation of glutamate transmission: An expanding role in stress
linked neuropathology.
AB - Chronic stress has been extensively linked to disturbances in glutamatergic
signalling. Emerging from this field of research is a considerable number of
studies identifying the ability of purines at the pre-, post-, and peri-synaptic
levels to tune glutamatergic neurotransmission. While the evidence describing
purinergic control of glutamate has continued to grow, there has been relatively
little attention given to how chronic stress modulates purinergic functions. The
available research on this topic has demonstrated that chronic stress can not
only disturb purinergic receptors involved in the regulation of glutamate
neurotransmission, but also perturb glial-dependent purinergic signalling. This
review will provide a detailed examining of the complex literature relating to
glutamatergic-purinergic interactions with a focus on both neuronal and glial
contributions. Once these detailed interactions have been described and
contextualised, we will integrate recent findings from the field of stress
research.
PMID- 29959964
TI - Mathematical modeling of dynamic behavior of fluid bilayer membranes under the
effect of density asymmetry.
AB - Shape transformations in biological membranes are crucial in a variety of
cellular processes such as transport in the Golgi apparatus and endoplasmic
reticulum, shaping the cell organelles and signaling in neuronal synapses.
Dynamic analysis of lipid bilayer membranes is popular among researchers as
valuable information about cell functions can be retrieved. There are several
limitations in experimental tests and simulations such as computational and
implementation cost while in theoretical studies, different phenomena can be
modeled and the effect of each parameter can be investigated. In this paper, a
continuum model including elastic energies and dissipation functions is utilized
with energy approach to obtain the governing equations of an enclosed lipid
bilayer membrane. The governing equations are solved numerically for vesicles
initially disturbed and the relaxation dynamics is studied. The stationary shape
of the vesicles for different values of reduced volume and reduced area
difference is obtained to explore the phase diagram and verify the governing
equations. Then, the density asymmetry in bilayers caused by the change in the
density or the equilibrium density of the outer monolayer is studied. This leads
to the formation of buds, tubules, and pearls. This can be observed in the
recruitment of proteins to the outer monolayer or pH gradients of the environment
of a vesicle. The effect of density difference and curvature on creation and
growth of tubules are investigated. An interesting metastable state in the
adsorption of the final bud due to the increase in the density of the outer
monolayer is observed in which the shape of the vesicle is almost unchanged. A
prolate vesicle relaxes toward an oblate or a stomatocyte vesicle when the
equilibrium density of the outer monolayer increases.
PMID- 29959965
TI - Fourth down and five.
AB - Binocular diplopia and right hemifacial numbness developed in a 52-year-old woman
after resection of a right temporal lobe glioblastoma. Based on the Parks
Bielschowsky 3-step test, she was diagnosed with a right cranial nerve (CN) IV
palsy in addition to right CN V dysfunction. Iatrogenic diplopia may result from
temporal lobe surgery due to the intimate relationship of CN IV and CN III to the
mesial temporal lobe. In addition, injury to CN V within Meckel cave is believed
to be the cause of facial numbness in some patients after temporal lobe surgery.
The anatomy of the intracranial portion of CN IV is reviewed, and the etiologies
of CN IV palsy are discussed.
PMID- 29959967
TI - Bactridine 2 effect in DRG neurons. Identification of NHE as a second target.
AB - Bactridine 2 (Bact-2) is an antibacterial toxin from Tityus discrepans venom
which modifies isoforms 1.2, 1.4 and 1.6 voltage-dependent sodium (Nav) channels.
Bactridine-induced Na+ outflow in Yersinia enterocolitica was blocked by
amiloride, suggesting that Bact-2 effect was mediated by an amiloride sensitive
sodium channel. In this study we show that Bact-2 increases also an outward
rectifying current in rat dorsal root ganglia (DRG) sensory neurons; therefore,
the nature of the outward rectifying currents was characterized and then the
effect of Bact-2 on these currents was studied. These currents are enhanced by
amiloride, are decreased by Na+ when an outward pH gradient is present and its
reversal potential coincides with that of a Cl-/H+ exchanger, suggesting that
rectifying currents are produced by the electrogenic Cl-/H+ exchanger modulated
by the Na+/H+ antiporter. Bact-2 also leads to an increase of the outward
currents in a similar way to the produced by the inhibition of the Na+/H+
exchanger. Additionally, the subsequent application of Bact-2 after blocking the
Na+/H+ exchanger does not produce any further effect, suggesting that Bact-2
modifies the outward current by modulating the activity of the Na+/H+ exchanger.
The effect of Bact-2 on pHi regulation was determined using the pH indicator
BCECF. The results show that the Na+/H+ exchanger is blocked by amiloride and Na+
free solutions and is modulated by Bact-2 in a similar way as cariporide. This
study validates that besides Nav channels, Bact-2 modulates the activity of the
Na+/H+ exchanger.
PMID- 29959966
TI - Language and cognitive control networks in bilinguals and monolinguals.
AB - Neuroimaging studies have reported overlapping neural circuits for cognitive
control when engaging in tasks that involve verbal and nonverbal stimuli in young
adult bilinguals. However, no study to date has examined the neural basis of
verbal and nonverbal task switching in both monolinguals and bilinguals due to
the inherent challenge of testing verbal task switching with monolinguals.
Therefore, it is not clear whether the finding for overlapping networks is unique
to bilingualism or indicative of general cognitive control. To address this
question, the current study compared functional neural activation for young
adults who were bilingual speakers of English and French or monolingual English
speakers who had limited French learning experience ("functional monolinguals")
on verbal and nonverbal task switching. Analyses showed common variance
explaining general cognitive control in task switching across verbal and
nonverbal domains for both groups, in line with the explanation that task
switching involves general cognitive control, as well as unique brain regions
recruited by monolinguals and bilinguals. Specifically, beyond the processing
common to the tasks, monolinguals also recruited distinct networks for each of
verbal and nonverbal switching but bilinguals used a common shared network. Thus,
the domain-general aspect of switching is different for monolinguals and
bilinguals.
PMID- 29959968
TI - Current technology for the industrial manufacture of snake antivenoms.
AB - Snake antivenoms are formulations of animal immunoglobulins used in the treatment
of snakebite envenomation. The general scheme for producing snake antivenoms has
undergone few changes since its development more than a century ago; however,
technological innovations have been introduced in the manufacturing process.
These medicines must comply with identity, purity, safety and efficacy profiles,
as requested by the current Good Manufacturing Practices (GMPs) applied to modern
biopharmaceutical drugs. Industrial production of snake antivenoms comprises
several stages, such as: 1) production of reference venom pools, 2) production of
hyperimmune plasma, 3) purification of the antivenom immunoglobulins, 4)
formulation of the antivenom, 5) stabilization of the formulation, and 6) quality
control of in-process and final products. In this work, a general review of the
existing technology used for the industrial manufacture of snake antivenoms is
presented.
PMID- 29959969
TI - Impact of tooth wear on masticatory performance.
AB - OBJECTIVE: Masticatory performance is influenced by a number of variables such as
age, gender, bite force, and occlusal units. Tooth wear may also play a role due
to changes in occlusal area and in vertical dimension of occlusion. The aim of
this study was to evaluate the effect of tooth wear on masticatory performance,
using a communition test. MATERIALS AND METHODS: Patients with different degrees
of tooth wear, referred by their general dental practitioners, and included in
the Radboud Tooth Wear Project, were approached for this study and included after
informed consent. The amount of post canine wear was scored with the Tooth Wear
Index (TWI). The number of occluding posterior units was quantified and the bite
force was measured using a transducer. Masticatory performance was measured with
a communition test, with the median particle size (X50) after 20 chewing cycles
as outcome measure. A multiple regression model was used to assess the relation
between TWI, age, gender, bite force, occlusal units and X50. RESULTS: 52
participants (40 male, 12 female, mean age: 40 +/- 8.2y) were included in the
study. The post canine TWI-score was between 1.0-3.3. The average number of
occlusal units per participant was 11.9 +/- 1.4 and the mean bite force 369 +/-
172 N. The mean X50 was 4.2 +/- 1.1. The results showed no significant relation
between post canine TWI-score, age, gender, bite force, and occlusal units upon
the X50 (p > 0.13). CONCLUSION: This study showed that the degree of tooth wear
could not be observed to have an effect on masticatory performance. CLINICAL
SIGNIFICANCE: On individual level an effect could be present but looking at a
larger group of patients, the degree of tooth wear did not have a relation with
masticatory performance as measured with a communition test.
PMID- 29959970
TI - Oxytocinergic modulation of brain activation to cues related to reproduction and
attachment: Differences and commonalities during the perception of erotic and
fearful social scenes.
AB - In animal research, the neuropeptide oxytocin (OT) has been known for its role in
reproduction and attachment for a longer time. There is strong evidence for an
involvement of the mesolimbic dopaminergic system for these effects of OT. In
contrast, human research rather concentrated on more human concepts of social
cognition and behavior (e.g. trust or processing of fearful faces) and mainly
focused on the amygdala as the main neurobiological substrate. To extend this
view, we wanted to gain more insight into the neurobiological effects of OT in
the context of reproduction and attachment in humans and compare these effects to
its well-known effects on fear processing. In a double-blind placebo-controlled
fMRI study, we investigated 55 healthy young men using intranasal OT
administration. During fMRI, participants saw attachment-related erotic scenes
and fearful social scenes. Over all participants, OT had a differential effect on
processing of erotic and fearful scenes. While OT administration led to a
relative increase of neural activation in mesolimbic structures during processing
of erotic stimuli, it decreased amygdala activation for fearful stimuli. On the
individual level, we observed significant positive correlations between OT
induced activation changes across different brain regions and under different
stimulus conditions. Our findings extend the already existing animal literature
and provide evidence for a similar involvement of the mesolimbic dopaminergic
system for OT effects in the context of reproduction and attachment in humans.
PMID- 29959971
TI - Molecular mechanisms underlying progesterone-induced cytoplasmic retention of p27
in breast cancer cells.
AB - It has been reported that progesterone (P4) can contribute to the aggressiveness
of human breast cancers through promoting cytoplasmic localization of p27 and
stimulating proliferation. However, the molecular mechanisms underlying P4
induced cytoplasmic retention of p27 are still unclear. Here, we demonstrated
that P4 (12.5-100 nM) concentration-dependently increased the number of T47D and
MCF-7 cells. P4 (50 nM) also time-dependently increased the levels of p27
protein. Knock-down of p27 using the small interfering RNA (siRNA) technique
abolished the P4-increased cell number of T47D and MCF-7. The signaling pathway
involved in the P4-promoted breast cancer cell proliferation was further
investigated. Our results suggest that P4 activated the PI3K/AKT-mediated
signaling, subsequently increasing phophorylation of p27 at pT198 and T157, and
thereby caused cytoplasmic retention of p27 protein. In addition, P4 activated
kinase-interacting stathmin (KIS), subsequently increasing phosphorylation of
nuclear p27 at serine 10 (S10), and thereby caused cytoplasmic translocation of
p27pS10 from the nucleus. P4 also increased the level of nuclear CDK2pT160,
thereby inducing p27 phosphorylation at T187, and hence caused cytosolic
translocation of p27pT187 from the nucleus. In the cytosol, both p27pS10 and
p27pT187 were degraded via the ubiquitin-proteasome pathway. Taken together, our
data suggest that P4 promoted breast cancer cell proliferation through
cytoplasmic retention of p27pT157 and p27pT198 and nuclear export of p27pS10 and
p27pT187.
PMID- 29959972
TI - Role of orexin-1 and orexin-2 receptors in the CA1 region of hippocampus in the
forced swim stress- and food deprivation-induced reinstatement of morphine
seeking behaviors in rats.
AB - Hippocampus (HIP) is an essential brain site to study reward-related learning
tasks, such as conditioning place preference (CPP) that can measure the
preference for environmental stimuli related to reward. Furthermore, orexin
neurons, situated exclusively in the lateral hypothalamus (LH) and link the
rewarding effects of drugs of abuse in the LH and the CA1 region of the HIP.
Therefore, in this study adult male rats were conditioned with morphine using a
CPP paradigm. After the eighth day of the extinction period, on the reinstatement
day, orexin-1 and orexin-2 receptor antagonists were administered bilaterally
into the CA1 region prior to acute stress. Using two different types of acute
stress, forced swim stress (FSS) and food deprivation (FD), the role of orexin-1
and orexin-2 receptors in the CA1 brain region in FSS and FD induced
reinstatement was investigated. Our results showed that application of the orexin
1 and orexin-2 antagonists, SB334867 and TCSOX2 29, respectively, reduced the CPP
scores in the reinstatement phase. Moreover, it can be concluded that orexin
neurons are activated in acute stress states, such as FSS and FD, as blocking the
orexin receptors, decreased the effects of acute stress in triggering the
reinstatement of morphine-CPP.
PMID- 29959973
TI - The role of the GLP-1/GLP-1R signaling pathway in regulating seizure
susceptibility in rats.
AB - OBJECTIVE: This study aimed to investigate the role of glucagon-like peptide-1
(GLP-1)/GLP-1 receptor(R) signaling in the regulation of seizure susceptibility
and to explore the potential mechanism in rats. METHODS: Hyperthermia-induced
seizures in SD rats were generated using hot bath methods, and seizure severity
was measured according to Racine scores and electroencephalogram (EEG). Protein
levels of GLP-1 and GLP-1R in the brain tissues of rats were evaluated through
ELISA, western blot analysis, and immunohistochemistry to explore the possible
roles of each in FS. Neuronal excitability, spontaneous inhibitory postsynaptic
currents (sIPSCs) and transient receptor potential cation channel subfamily V
member 1(TRPV1) currents were tested using the patch-clamp method in cultured
hippocampal neurons. RESULT: Significant decreases in the levels of GLP-1 and GLP
1R were observed in the hippocampi of rats compared to those in the control
group. Furthermore, treatment with the GLP-1R pharmacological inhibitor exendin9
39 increased hyperthermia- induced seizure severity in rats and promoted neuronal
firing activity in cultured neurons. Importantly, exendin9-39 and GLP-1R
knockdown decreased the amplitude and frequency of sIPSCs in cultured neurons. In
addition, GLP-1R knockdown elevated downstream TRPV1 expression and promoted
capsaicin-induced TRPV1 function, which may regulate inhibitory neurotransmission
to affect seizure susceptibility. CONCLUSION: The present study suggests that
inhibition of GLP-1R signaling promotes seizure activity, which plays a key role
in the pathogenesis of FS.
PMID- 29959974
TI - Neuroprotection by ethanolic extract of Syzygium aromaticum in Alzheimer's
disease like pathology via maintaining oxidative balance through SIRT1 pathway.
AB - The oxidative stress plays a key role in Alzheimer's disease (AD) and Sirtuin
(SIRT1) is potential mediator of oxidative pathway. This study explored the role
of Syzygium aromaticum on SIRT1 and oxidative balance in amyloid beta induced
toxicity. Anti-oxidative capacity of Syzygium aromaticum was performed in Abeta25
35 induced neurotoxicity in neuronal cells. Superoxide dismutase, Catalase and
Glutathione enzyme activity were determined by the treatment of Syzygium
aromaticum. Both recombinant and endogenous SIRT1 activity were performed in its
presence. The expression of gamma-secretase and SIRT1 were evaluated by western
blot. Syzygium aromaticum was capable to scavenge ROS and elevate the percentage
of anti-oxidant enzymes. It also activated and elevated the level of SIRT1 and
downregulated gamma-secretase level. These findings show a holistic approach
towards the neurodegenerative disease management by Syzygium aromaticum which
could lead to the formulation of new drug for AD. This Ayurvedic product can give
a healthy aging with no side effects and also be cost effectives. It may meet
unmet medical needs of current relevance.
PMID- 29959975
TI - Embryonic intraventricular transplantation of neural stem cells augments
inflammation-induced prenatal brain injury.
AB - OBJECTIVE: Prenatal brain injury results from undesirable circumstances during
the embryonic development. Current endeavors for treating this complication are
basically excluded to postnatal therapeutic approaches. Neural stem cell therapy
has shown great promise for treating neurodevelopmental disorders. To our
knowledge, this is the first study that investigates the therapeutic effect of in
utero transplantation of neural stem cells (NSCs) in inflammation model of
prenatal brain injury. METHODS: To induce prenatal injury, time-mated C57BL6J
mice were intraperitoneally injected with 50 MUg/kg lipopolysaccharide (LPS(on
the day 15 of gestation. In the treatment group, NSCs were transplanted into the
lateral ventricle of embryos on day 17 of gestation. The expression of GFAP, Iba
1, Olig2, and NeuN were assessed by real time PCR and immunohistochemistry.
Changes in IL-6, TNF-alpha and IL-10 cytokines level, and caspase 3 activity were
evaluated in the cortex of pups. RESULTS: Intrauterine transplanted NSCs homed to
the brain cortex of offspring. Brain levels of pro-inflammatory cytokines showed
a significant downward trend in the NSCs group. Furthermore, NSCs ameliorated
inflammation-induced reactive microgliosis and astrogliosis as well as cellular
degeneration. Apoptosis inhibition in the treated group was demonstrated by the
decline in the caspase 3 activity and dark neurons. CONCLUSION: This study
suggests a promising prospect to initiate the treatment of prenatal brain injury
before birth by intrauterine transplantation of NSCs.
PMID- 29959976
TI - PTEN expression responds to transcription factor POU and regulates p-AKT levels
during diapause initiation in the cotton bollworm, Helicoverpa armigera.
AB - Diapause is a complex physiological response accompanied by many signaling
pathways participating in the process. Previous studies have shown that p-AKT
levels in brains of diapause-destined pupae are elevated by ROS, and the
activated AKT promotes Glut expression for glucose uptake during diapause entry
in Helicoverpa armigera. However, the mechanism by which ROS activate AKT is
still unclear. Here, we show that PTEN, a PI3K/p-AKT signaling inhibitor, was
significantly lower in the brains of diapause-destined pupae and that p-AKT
levels were elevated by a lack of PTEN dephosphorylating PIP3. In addition, POU
was identified as a transcription factor that binds to the PTEN promoter and
regulates its expression. POU expression was enhanced by ecdysone but suppressed
by ROS, suggesting that POU/PTEN plays a central role in responding to ROS
signaling and regulating p-AKT levels. These results suggest that ecdysone and
ROS participate together in the regulation of insect diapause through
downregulation of POU/PTEN, which elevates p-AKT levels.
PMID- 29959977
TI - Transcriptome-wide survey, gene expression profiling and exogenous chemical
induced transcriptional responses of cytochrome P450 superfamily genes in
migratory locust (Locusta migratoria).
AB - Cytochrome P450 monooxygenases (CYPs) belong to a large superfamily of heme
containing enzymes catalyzing at least 60 different types of chemically distinct
reactions. Insect CYPs play key roles in biotransformation of insecticides and
plant chemicals, and are implicated in insecticide resistance and insect
adaptation to their host plants. Insect CYPs are well studied in model insects,
but little is known about the CYP superfamily in paurometabolous insects. We
employed Illumina sequencing technology to identify 71 partial and 78 full-length
open reading frames (ORFs) of LmCYP genes from the migratory locust (Locusta
migratoria), one of the most destructive paurometabolous insect pests in the
world. Seventy-eight LmCYPs with complete ORFs were formally named and classified
into 19 families and 43 subfamilies. The majority of LmCYPs were mainly expressed
in nymphal and adult stages, but LmCYP expression varied widely among thirteen
different tissues examined. Regulatory elements were predicted in the promoter
regions of LmCYP genes, and subsequent exposure of locusts to 12 different
exogenous chemicals showed that 2-tridecanone and xanthotoxin were the most
effective at increasing LmCYP expression. Our results represent the first
transcriptome-wide analysis of the LmCYP superfamily from migratory locust, and
provide a foundation for understanding the physiological functions, functional
diversity, evolution, and regulatory mechanisms controlling the expression of the
CYP gene superfamily in the locust.
PMID- 29959978
TI - Prolactin controls Na+,Cl- cotransporter via Stat5 pathway in the teleost gill.
AB - In some freshwater fish species, the control of gill Na, Cl cotransporter (Ncc2b)
by prolactin appears to be instrumental to ionic homeostasis. This study was
carried out to examine the signaling pathways involved in prolactin-mediated salt
retention using gill explants from Japanese medaka (Oryzias latipes). Ovine
prolactin induced a concentration-dependent stimulation of ncc2b with significant
effects of 10, 100 and 1000 ng of hormone per mL media (2-6 fold). To understand
the molecular mechanisms mediating prolactin control of gill function, we
analyzed effects on signaling pathways known to be involved in the hormones
action in other systems, namely Stat5, Akt and Erk1/2. Their activation was
examined in a time course and concentration response experiment. Prolactin (1 MUg
mL-1) induced a rapid phosphorylation (stimulation) of Stat5 (10 min) that
reached a plateau after 30 min and was maintained for at least 120 min. The
effect of prolactin on Stat5 phosphorylation was concentration-dependent (4-12
fold). No activation of Akt or Erk1/2 was observed in either experiment. The
Stat5 activation was further investigated in localization studies that
demonstrated strong nuclear expression of phosphorylated Stat5 in prolactin
treated gill ionocytes. Using specific inhibitors, we analyzed the signalling
pathways mediating prolactin induction of gill ncc2b. Co-incubation experiments
showed that Stat5 inhibition blocked prolactin's stimulation of ncc2b expression,
while PI3K-Akt and Mek1/2-Erk1/2 pathway inhibitors had no effect. These findings
show that ncc2b expression is dependent on prolactin's downstream activation of
Stat5 and its subsequent nuclear translocation within branchial ionocytes.
PMID- 29959980
TI - Bone morphogenetic protein 4 expression in the developing lumbosacral spinal cord
of rat embryos with anorectal malformations.
AB - Although there are improvements in treatment of anorectal malformations (ARMs),
patients can still develop fecal incontinence, constipation, and soiling with
loss in quality of life. Recent evidence suggests that malformations in the
lumbosacral spinal cord are one of the factors that affect postoperative
anorectal function. However, the underlying mechanism that produces these
malformations has yet to be elucidated. The bone morphogenetic proteins (BMPs)
comprise a large group of highly conserved molecules that are involved in
multiple processes and play important roles in the formation, development, and
differentiation of the spinal cord. This study was designed to investigate the
levels of BMP4 expression in the lumbosacral spinal cord in ARMs rat embryos
induced by ethylenethiourea (ETU). Specifically, we assessed the association of
BMP4 levels with the maldevelopment of the lumbosacral spinal cord and whether
BMP4 acted through the canonical intracellular pathway in embryonic rats with
ARMs. BMP4 expression was confirmed with immunohistochemical staining, RT-qPCR
and western blot analyses of embryonic day (E) 16, E17, E19 and E21 embryos,
moreover Smad1/5 and pSmad1/5 expression were confirmed with western blot
analyses at peak time point of BMP4 expression. Our results reveal that BMP4
expression in the lumbosacral spinal cord of ARMs rat embryos is decreased at
both the mRNA and protein levels and could decrease the phosphorylation of
smad1/5, when compared with their expression levels in normal tissue. These
results also suggest that reductions in BMP4 expression were possibly responsible
for dysfunction of the lumbosacral spinal cord during late developmental stages
in ARMs fetal rats. Taken together, we conclude a role for BMP4 in the
pathogenesis of lumbosacral spinal cord maldevelopment in developing ARMs rats.
PMID- 29959979
TI - M3-subtype muscarinic receptor activation stimulates intracellular calcium
oscillations and aldosterone production in human adrenocortical HAC15 cells.
AB - A previous body of work in bovine and rodent models shows that cholinergic
agonists modulate the secretion of steroid hormones from the adrenal cortex. In
this study we used live-cell Ca2+ imaging to investigate cholinergic activity in
the HAC15 human adrenocortical carcinoma cell line. The cholinergic agonists
carbachol and acetylcholine triggered heterogeneous Ca2+ oscillations that were
strongly inhibited by antagonists with high affinity for the M3 muscarinic
receptor subtype, while preferential block of M1 or M2 receptors was less
effective. Acute exposure to carbachol and acetylcholine modestly elevated
aldosterone secretion in HAC15 cells, and this effect was also diminished by M3
inhibition. HAC15 cells expressed relatively high levels of mRNA for M3 and M2
receptors, while M1 and M5 mRNA were much lower. In conclusion, our data extend
previous findings in non-human systems to implicate the M3 receptor as the
dominant muscarinic receptor in the human adrenal cortex.
PMID- 29959981
TI - Immature sleep pattern in newborn rats when dams encountered sleep restriction
during pregnancy.
AB - There is a growing realization that proper sleep during pregnancy is essential
for the health of the mother and the offspring. However, there are no reports on
the effects of maternal sleep restriction on the sleep-wake profiles of newborns.
So, this study was conducted to evaluate the effects of sleep restriction during
the third term of pregnancy on the sleep-wake profiles of neonates born to them.
The female pregnant Wistar rats were sleep restricted for 5 h/day on gestational
days 15-20 by gentle handling. Sleep-wake profiles of the pups born to them and
to the control rats were recorded on postnatal days 1-21. Pups of sleep
restricted dams had higher active sleep (AS) and lower quiet sleep (QS) as well
as wakefulness. Higher ratio of AS to QS, longer duration of sleep cycles, lesser
bout frequency and reduced EEG delta power were also observed in these pups, all
of which indicated brain immaturity. All these signs of delayed maturation,
usually found in premature babies, were observed in the pups of sleep restricted
mothers, who had longer gestation period. This report not only shows the
importance of sleep during pregnancy, but it also suggests that neonatal sleep
monitoring can be used as a tool for early assessment of retarded brain
development.
PMID- 29959982
TI - Analysis of the conserved NER helicases (XPB and XPD) and UV-induced DNA damage
in Hydra.
AB - BACKGROUND: Nucleotide excision repair (NER) pathway is an evolutionarily
conserved mechanism of genome maintenance. It detects and repairs distortions in
DNA double helix. Xeroderma Pigmentosum group B (XPB) and group D (XPD) are
important helicases in NER and are also critical subunits of TFIIH complex. We
have studied XPB and XPD for the first time from the basal metazoan Hydra which
exhibits lack of organismal senescence. METHODS: In silico analysis of proteins
was performed using MEGA 6.0, Clustal Omega, Swiss Model, etc. Gene expression
was studied by in situ hybridization and qRT-PCR. Repair of CPDs was studied by
DNA blot assay. Interactions between proteins were determined by co-
immunoprecipitation. HyXPB and HyXPD were cloned in pET28b, overexpressed and
helicase activity of purified proteins was checked. RESULTS: In silico analysis
revealed presence of seven classical helicase motifs in HyXPB and HyXPD. Both
proteins revealed polarity-dependent helicase activity. Hydra repairs most of the
thymine dimers induced by UVC (500 J/m2) by 72 h post-UV exposure. HyXPB and
HyXPD transcripts, localized all over the body column, remained unaltered post-UV
exposure indicating their constitutive expression. In spite of high levels of
sequence conservation, XPB and XPD failed to rescue defects in human XPB- and XPD
deficient cell lines. This was due to their inability to get incorporated into
the TFIIH multiprotein complex. CONCLUSIONS: Present results along with our
earlier work on DNA repair proteins in Hydra bring out the utility of Hydra as
model system to study evolution of DNA repair mechanisms in metazoans.
PMID- 29959984
TI - Phylogenetic relationships of the conoidean snails (Gastropoda: Caenogastropoda)
based on mitochondrial genomes.
AB - With more than 5,000 species, Conoidea is one of the most diversified
superfamilies of Gastropoda. Recently, the family-level classification of these
venomous predator snails has undergone substantial changes, on the basis of a
phylogenetic tree reconstructed combining partial mitochondrial and nuclear gene
sequences, and up to 16 families are now recognized. However, phylogenetic
relationships among these families remain largely unresolved. Here, we sequenced
20 complete or nearly complete mitochondrial (mt) genomes, which were combined
with mt genomes available in GenBank to construct a dataset that included
representatives of 80% of the known families, although for some we had only one
species or genus as representative. Most of the sequenced conoidean mt genomes
shared a constant genome organization, and observed rearrangements were limited
exclusively to tRNA genes in a few lineages. Phylogenetic trees were
reconstructed using probabilistic methods. Two main monophyletic groups, termed
"Clade A" and "Clade B", were recovered with strong support within a monophyletic
Conoidea. Clade A (including families Clavatulidae, Horaiclavidae, Turridae s.s.,
Terebridae, Drilliidae, Pseudomelatomidae, and Cochlespiridae) was composed of
four main lineages, one of which was additionally supported by a rearrangement in
the gene order. Clade B (including families Conidae, Borsoniidae, Clathurellidae,
Mangeliidae, Raphitomidae, and Mitromorphidae) was composed of five main
lineages. The reconstructed phylogeny rejected the monophyly of Clavatulidae,
Horaiclavidae, Turridae, Pseudomelatomidae, and Conidae, indicating that several
of the currently accepted families may be ill-defined. The reconstructed tree
also revealed new phylogenetic positions for genera characterized as tentative
(Gemmuloborsonia, Lucerapex, and Leucosyrinx), enigmatic (Marshallena) or
challenging to place (Fusiturris), which will potentially impact the
classification of the Conoidea.
PMID- 29959985
TI - Understanding effects of process parameters and forced feeding on die filling.
AB - Die filling is a critical step during pharmaceutical tablet production and is
still not well understood due to the rather complex interplay between particle
attributes, die orifice diameter and fill energetics. While shoe-die filling
models have been used to simulate die filling conditions, they typically lack the
sophistication of the actual production-scale, feeder-based die filling
conditions. The relationship between tableting process parameters and filling
into die orifices of different diameters by powders of different flowabilities
requires critical examination and understanding. In this study, a special die
filling contraption was designed and custom-made to simulate the effects of
gravity, suction and feeder paddle assistance as present in modern rotary tablet
presses. Die fill performance was studied using powders with different flow
properties. Suction impact was greatest on die fill, in particular, for small
orifice diameters and less permeable powders. Effect of paddle velocity on die
fill was greater for compressible powders and larger orifice diameters. In
comparison to suction and paddle velocity, forced feeding did not significantly
affect die fill performance. Relationship between process parameters and die fill
performance was found to be highly dependent on the material and orifice
diameter.
PMID- 29959986
TI - Inhibition of Nrf2 alters cell stress induced by chronic iron exposure in human
proximal tubular epithelial cells.
AB - Iron can catalyze reactive oxygen species (ROS) formation, causing cellular
injury. In systemic iron overload, renal tubular epithelial cells are luminally
exposed to high iron levels due to glomerular filtration of increased circulating
iron. Reports of tubular dysfunction and iron deposition in beta-thalassemia
major support an association between increased chronic iron exposure and renal
tubular injury. In acute iron exposure, Nuclear factor-erythroid 2-related factor
2 (Nrf2) may protect from iron-induced injury, whereas chronic renal stress may
lead to Nrf2 exhaustion. We studied the cytotoxic mechanisms of chronic iron
exposure using human conditionally immortalized proximal tubular epithelial cells
(ciPTECs). Long-term iron exposure resulted in iron accumulation, cytosolic ROS
formation and increased heme oxygenase 1 (HMOX-1) mRNA expression (all p <
0.001). This was accompanied by nuclear translocation of Nrf2 and induction of
its target protein NQO1, which both could be blocked by the Nrf2 inhibitor
trigonelline. Interestingly, iron and trigonelline incubation reduced ROS
production, but did not affect HMOX-1 mRNA levels. Moreover, ferritin protein and
CHOP mRNA expression were induced in combined iron and trigonelline incubated
cells (p < 0.05). Together, these findings suggest that chronic iron exposure
induces oxidative stress and that exhaustion of the antioxidant Nrf2 pathway may
lead to renal injury.
PMID- 29959983
TI - Stochastic simulations of nanoparticle internalization through transferrin
receptor dependent clathrin-mediated endocytosis.
AB - BACKGROUND: Receptor dependent clathrin-mediated endocytosis (CME) is one of the
most important endocytic pathways for the internalization of bioparticles into
cells. During CME, the ligand-receptor interactions, development of clathrin
coated pit (CCP) and membrane evolution all act together to drive the
internalization of bioparticles. In this work, we develop a stochastic
computational model to investigate the CME based on the Metropolis Monte Carlo
simulations. METHODS: The model is based on the combination of a stochastic
particle binding model with a membrane model. The energetic costs of membrane
bending, CCP formation and ligand-receptor interactions are systematically linked
together. RESULTS: We implement our model to investigate the effects of particle
size, ligand density and membrane stiffness on the overall process of CME from
the drug delivery perspectives. Consistent with some experiments, our results
show that the intermediate particle size and ligand density favor the particle
internalization. Moreover, our results show that it is easier for a particle to
enter a cell with softer membrane. CONCLUSIONS: The model presented here is able
to provide mechanistic insights into CME and can be readily modified to include
other important factors, such as actins. The predictions from the model will aid
in the therapeutic design of intracellular/transcellular drug delivery and
antiviral interventions.
PMID- 29959988
TI - Genetic and metabolic hallmarks of clear cell renal cell carcinoma.
AB - Clear cell renal cell carcinoma (ccRCC) is a malignancy characterized by
deregulated hypoxia-inducible factor signaling, mutation of several key chromatin
modifying enzymes, and numerous alterations in cellular metabolism. Pre-clinical
studies have historically been limited to cell culture models, however, the
identification of critical tumor suppressors and oncogenes from large-scale
patient sequencing data has led to several new genetically engineered mouse
models with phenotypes reminiscent of ccRCC. In this review, we summarize recent
literature on these topics and discuss how they inform targeted therapeutic
approaches for the treatment of ccRCC.
PMID- 29959987
TI - TLR2 and TLR3 expression as a biomarker for the risk of doxorubicin-induced heart
failure.
AB - Doxorubicin (Dox) is limited in its use because of its adverse effect of inducing
irreversible heart dysfunction. Innate immune factors, including toll-like
receptors (TLRs), play important roles in most cardiac diseases and doxorubicin
induced cardiotoxicity. In this study, subjects were divided into the following
groups: healthy controls (n = 62), HF group (n = 60), Dox group (n = 82), and Dox
HF group (n = 32). Expressions of TLR mRNAs in peripheral blood mononuclear cells
were detected by RT-PCR. Western blotting was used to quantify protein
expressions of Peripheral blood mononuclear cells (PBMCs) TLRs and their
downstream signal proteins. The release of inflammatory factors was detected by
ELISA. Results indicated that TLR2 was increased and TLR3 was decreased between
the control group and Dox group, and between the Dox group and Dox-HF group.
Serum inflammatory factors were comparable between the HF group, the Dox group,
and the Dox-HF group. This study suggested that TLR2 and TLR3 are up- and down
regulated, respectively, in doxorubicin-treated patients who develop heart
dysfunctions. This may suggest a predictive role for TLR2-TLR3 imbalance in
doxorubicin-induced heart failure.
PMID- 29959989
TI - Metabolic reprogramming for cancer cells and their microenvironment: Beyond the
Warburg Effect.
AB - While metabolic reprogramming of cancer cells has long been considered from the
standpoint of how and why cancer cells preferentially utilize glucose via aerobic
glycolysis, the so-called Warburg Effect, the progress in the following areas
during the past several years has substantially advanced our understanding of the
rewired metabolic network in cancer cells that is intertwined with oncogenic
signaling. First, in addition to the major nutrient substrates glucose and
glutamine, cancer cells have been discovered to utilize a variety of
unconventional nutrient sources for survival. Second, the deregulated biomass
synthesis is intertwined with cell cycle progression to coordinate the
accelerated progression of cancer cells. Third, the reciprocal regulation of
cancer cell's metabolic alterations and the microenvironment, involving extensive
host immune cells and microbiota, have come into view as critical mechanisms to
regulate cancer progression. These and other advances are shaping the current and
future paradigm of cancer metabolism.
PMID- 29959990
TI - Preclinical models for precision oncology.
AB - Precision medicine approaches have revolutionized oncology. Personalized
treatments require not only identification of the driving molecular alterations,
but also development of targeted therapies and diagnostic tests to identify the
appropriate patient populations for clinical trials and subsequent therapeutic
implementation. Preclinical in vitro and in vivo models are widely used to
predict efficacy of newly developed treatments. Here we discuss whether, and to
what extent, preclinical models including cell lines, organoids and tumorgrafts
recapitulate key features of human tumors. The potential of preclinical models to
anticipate treatment efficacy and clinical benefit is also presented, using
examples in different tumor types.
PMID- 29959991
TI - Characterization of inter-crystallite peptides in human enamel rods reveals
contribution by the Y allele of amelogenin.
AB - Proteins of the inter-rod sheath and peptides within the narrow inter-crystallite
space of the rod structure are considered largely responsible for visco-elastic
and visco-plastic properties of enamel. The present study was designed to
investigate putative peptides of the inter-crystallite space. Entities of 1-6 kDa
extracted from enamel rods of erupted permanent teeth were analysed by mass
spectrometry (MS) and shown to comprise N-terminal amelogenin (AMEL) peptides
either containing or not containing exon 4 product. Other dominant entities
consisted of an N-terminal peptide from ameloblastin (AMBN) and a series of the
most hydrophobic peptides from serum albumin (ALBN). Amelogenin peptides encoded
by the Y-chromosome allele were strongly detected in Enamel from male teeth.
Location of N-terminal AMEL peptides as well as AMBN and ALBN, between apatite
crystallites, was disclosed by immunogold scanning electron microscopy (SEM).
Density plots confirmed the relative abundance of these products including exon
4+ AMEL peptides that have greater capacity for binding to hydroxyapatite.
Hydrophilic X and Y peptides encoded in exon 4 differ only in substitution of non
polar isoleucine in Y for polar threonine in X with reduced disruption of the
hydrophobic N-terminal structure in the Y form. Despite similarity of X and Y
alleles of AMEL the non-coding region upstream from exon 4 shows significant
variation with implications for segregation of processing of transcripts from
exon 4. Detection of fragments from multiple additional proteins including
keratins (KER), fetuin A (FETUA), proteinases and proteinase inhibitors, likely
reflect biochemical events during enamel formation.
PMID- 29959992
TI - Oleocanthal and oleacein contribute to the in vitro therapeutic potential of
extra virgin oil-derived extracts in non-melanoma skin cancer.
AB - Although the anticancer properties of extra virgin olive oil (EVOO) extracts have
been recognized, the role of single compounds in non-melanoma skin cancer is
still unknown. The in vitro chemopreventive and anticancer action of EVOO
extracts and oil-derived compounds in non-melanoma skin cancer models were
evaluated on cutaneous squamous cell carcinoma cells and on immortalized human
keratinocytes stimulated with epidermal growth factor. Preparation of EVOO
extracts and isolation of single compounds was carried out by chromatographic
methods. Antitumor activity was assessed by cell-based assays (cell viability,
migration, clonogenicity, and spheroid formation) and apoptosis documented by
internucleosomal DNA fragmentation. Finally, inhibition of key oncogenic
signaling nodes involved in the progression from actinic keratosis to cutaneous
squamous cell carcinoma was studied by western blot. EVOO extracts reduced non
melanoma skin cancer cell viability and migration, prevented colony and spheroid
formation, and inhibited proliferation of atypical keratinocytes stimulated with
epidermal growth factor. Such a pharmacological activity was promoted by
oleocanthal and oleacein through the inhibition of Erk and Akt phosphorylation
and the suppression of B-Raf expression, whereas tyrosol and hydroxytyrosol did
not have effect. The current study provides in vitro evidence for new potential
clinical applications of EVOO extracts and/or single oil-derived compounds in the
prevention and treatment of non-melanoma skin cancers.
PMID- 29959993
TI - Label-free cell signaling pathway deconvolution of angiotensin type 1 receptor
reveals time-resolved G-protein activity and distinct AngII and AngIIIIV
responses.
AB - Angiotensin II (AngII) type 1 receptor (AT1R) is a G protein-coupled receptor
known for its role in numerous physiological processes and its implication in
many vascular diseases. Its functions are mediated through G protein dependent
and independent signaling pathways. AT1R has several endogenous peptidic
agonists, all derived from angiotensinogen, as well as several synthetic ligands
known to elicit biased signaling responses. Here, surface plasmon resonance (SPR)
was used as a cell-based and label-free technique to quantify, in real time, the
response of HEK293 cells stably expressing the human AT1R. The goal was to take
advantage of the integrative nature of this assay to identify specific signaling
pathways in the features of the response profiles generated by numerous
endogenous and synthetic ligands of AT1R. First, we assessed the contributions of
Gq, G12/13, Gi, Gbetagamma, ERK1/2 and beta-arrestins pathways in the cellular
responses measured by SPR where Gq, G12/Rho/ROCK together with beta-arrestins and
ERK1/2 were found to play significant roles. More specifically, we established a
major role for G12 in the early events of the AT1R-dependent response, which was
followed by a robust ERK1/2 component associated to the later phase of the
signal. Interestingly, endogenous AT1R ligands (AngII, AngIII and AngIV)
exhibited distinct responses signatures with a significant increase of the ERK1/2
like components for both AngIII and AngIV, which points toward possibly distinct
physiological roles for the later. We also tested AT1R biased ligands, all of
which affected both the early and later events. Our results support SPR-based
integrative cellular assays as a powerful approach to delineate the contribution
of specific signaling pathways for a given cell response and reveal response
differences associated with ligands with distinct pharmacological properties.
PMID- 29959994
TI - The first complete mitochondrial genome of the Japanese beetle Popillia japonica
(Coleoptera: Scarabaeidae) and its phylogenetic implications for the superfamily
Scarabaeoidea.
AB - Popillia japonica is a harmful pest with a wide range of hosts, presenting
particular dangers to golf courses, lawns, and pastures. Very limited molecular
data for Po. japonica are available in GenBank, including only some partial
nuclear gene or mitochondrial gene sequences, and acquiring more molecular
information is urgent for studying the diagnosis of infestation, phylogeny, and
evolution of this beetle. Herein, we characterize the complete mitochondrial
genome of Po. japonica using next-generation sequencing and describe its
structural features. The circular mitochondrial genome of Po. japonica is 16,541
bp in size, containing thirteen protein-coding genes (PCGs), two ribosomal RNA
genes (rRNAs), twenty-two transfer RNA genes (tRNAs), and a control region. The
base composition of the whole mitochondrial genome of Po. japonica is 39.00%,
9.50%, 14.80%, and 36.70% for A, G, C, and T, respectively, demonstrating high A
+ T content (75.70%). Phylogenetic relationships of the superfamily Scarabaeoidea
show that Po. japonica and Protaetia brevitarsis form in a clade that is a sister
group to Rhopaea magnicornis and Polyphylla laticollis from Melolonthinae.
Cheirotonus jansoni from Melolonthinae is a sister group with Po. japonica,
Protaetia brevitarsis, Rhopaea magnicornis and Polyphylla laticollis, indicating
that Melolonthinae is a polyphyletic group. This is the first report of a
complete mitochondrial genome of Po. japonica and it will contribute to further
studies of infestation diagnosis, phylogeny, and evolution of Scarabaeoidea.
PMID- 29959996
TI - Citric acid crosslinked carboxymethylcellulose-poly(ethylene glycol) hydrogel
films for delivery of poorly soluble drugs.
AB - In present work, carboxymethylcellulose (CMC) - polyethylene glycol (PEG)
hydrogel films were prepared using citric acid as a non-toxic crosslinking agent,
for the controlled delivery of model hydrophobic drug (ketoconazole). The
carboxyl content of the hydrogel films were determined by acid-base titration.
The films were characterized by solid state 13C NMR, ATR-FTIR, TGA and DSC, and
evaluated for swelling behavior, drug loading, drug release, hemocompatibility,
in vitro cytotoxicity and implantation test. An increase in the amount of PEG
caused increase in the carboxyl content and swellability of the hydrogel films.
The solid state 13C NMR, ATR-FTIR and thermal analysis confirmed the formation of
ester crosslinks in between CMC and PEG in the hydrogel films. The release of KTZ
was found to be retarded due to presence of grafted PEG in the hydrogel films.
The hydrogel films exhibited excellent hemocompatibility and cytocompatibility.
Implantation test revealed that the hydrogel films caused minimum inflammation.
From the overall results, citric acid crosslinked CMC-PEG hydrogel films were
found to be suitable for enhanced loading and controlled release of the poorly
soluble drugs.
PMID- 29959995
TI - Orientin-mediated Nrf2/HO-1 signal alleviates H2O2-induced oxidative damage via
induction of JNK and PI3K/AKT activation.
AB - Oxidative stress is closely associated with the pathogenesis of various diseases.
Orientin (Ori), a flavonoid component isolated from natural plants, possesses
antioxidant activity. Accordingly, we focused on exploring the potential
therapeutic effects of Ori on hydrogen peroxide (H2O2)-induced oxidative
impairment in RAW 264.7 cells and the underlying antioxidative mechanisms. Our
findings suggested that Ori exposure effectively alleviated H2O2-stimulated
cytotoxicity, inhibited reactive oxygen species (ROS) generation, and glutathione
(GSH) depletion, which were involved in induction of heme oxygenase-1 (HO-1) by
enhancing the nuclear factor-erythroid 2-related factor 2 (Nrf2) translocation,
decreasing the Keap1 protein expression, and increasing the antioxidant response
element (ARE) activity. However, knockdown of Nrf2 and HO-1 with siRNA mostly
abolished the cytoprotective effects against H2O2-induced cell oxidative injury,
reduced the expression of Nrf2 and HO-1, respectively. Moreover, Ori exposure
significantly induced a c-Jun NH2-terminal kinase (JNK) and phosphatidylinositol
3-kinase (PI3K)/serine/threonine kinase (AKT) phosphorylation, but JNK and
PI3K/AKT inhibitors treatment effectively reduced levels of Ori-enhanced Nrf2
nuclear translocation and HO-1 protein expression, and blocked Ori-inhibited
cytotoxicity and ROS accumulation triggered by H2O2 respectively. Taken together,
Ori might exhibit a protective role against H2O2-stimulated oxidative damage by
the induction of HO-1 expression through the activation of the JNK- and PI3K/AKT
Nrf2 signaling pathways.
PMID- 29959997
TI - Preparation, characterization and in vitro release study of beta
cyclodextrin/chitosan nanoparticles loaded Cinnamomum zeylanicum essential oil.
AB - Cinnamomum zeylanicum essential oil (CEO) is an effective antimicrobial agent.
However, its high volatile nature and low stability require an efficient
encapsulation system for drug delivery applications. We herein report the
synthesis of beta-cyclodextrin modified chitosan (beta-CD/CS) nanoparticles
binary system via ionic gelation method for the controlled release of CEO. The
nanoparticles were characterized by optical and structural spectroscopies
followed by the in-vitro released study. The results showed that the particles
are spherical in shape with positively charged surface and maximum encapsulation
efficiency of 58.03%. In vitro release profiles showed an overall CEO release of
71% for the binary system compared to 49% for CEO- loaded chitosan (CS)
nanoparticles single system. The release mechanism followed Fickian behaviour
while in vitro CEO release analysis showed a sustained and controlled release for
over 120 h. The as-synthesized beta-cyclodextrin/chitosan nanoparticles offer a
promising system for enhancing the therapeutic effect of CEO.
PMID- 29959998
TI - Energy drink and alcohol combination leads to kidney and liver alterations in
rats.
AB - The aim of this study was to evaluate the acute toxicity of the association of
energy drink and alcohol in male Wistar rats. Animals were treated by oral gavage
with 10 ml/kg distilled water (control); 10 ml/kg energy drink (ED10); 3.2 mg/kg
caffeine + 40 mg/kg taurine; 2 g/kg alcohol 20%; 2 g/kg alcohol 20% + ED10; and 2
g/kg alcohol 20% + 3.2 mg/kg caffeine + 40 mg/kg taurine. Behavioral alterations
were observed for 6 h after treatment. Animals presented significant differences
in the frequency of rearing, ambulation, grooming, wakefulness and tachypnea
along time. Caffeine + taurine increased the levels of TBARS and total thiols in
kidneys. ED10 increased lipoperoxidation in liver. The association of ED10 +
alcohol induced nephrotoxicity observed by the increase of urinary N-acetyl-beta
d-glucosaminidase (NAG) activity. Histopathological analysis showed the presence
of congestion and hydropic and hyaline degenerations in the livers of ED10 +
alcohol treated rats, and hemorrhage in the liver of alcohol + caffeine + taurine
group. In kidneys, hyaline degeneration was observed in ED10; ED10 + alcohol;
caffeine + taurine; and alcohol + caffeine + taurine. Hemorrhage was present in
the kidneys of all groups. The combination of energy drinks and alcohol is not
safe for the consumers. Therefore, precautionary measures should be disseminated
among risk populations, especially the teenagers.
PMID- 29959999
TI - Measuring EMPs in the lung what can be measured in the lung: Asbestiform minerals
and cleavage fragments.
AB - Asbestos mineral fibers have been associated with the development of a variety of
diseases in humans and experimental animals, including asbestosis, lung cancer,
and mesothelioma. Asbestos includes several mineral types divided into two
mineral groups, serpentine and amphibole forms. Chrysotile is the serpentine
mineral classified as asbestos, whereas the amphiboles include amosite,
crocidolite, tremolite, actinolite and anthophyllite. There are a number of
mineral fibers that occur with asbestiform morphology and that have been
associated with various asbestos-induced diseases. These include the Libby
amphiboles (associated with a vermiculite mine northwest of Libby, MT), erionite
(in Turkey and North America), fluoro-edenite (in Sicily), and perhaps
balangeroite (in Italy). In addition, each of the asbestos minerals occurs in a
non-fibrous form, and these may occur as cleavage fragments that satisfy the
definition for a fiber, i.e., particles with an aspect ratio of at least 3:1 and
roughly parallel sides. Cleavage fragments of non-asbestiform minerals have not
been associated with asbestos-induced diseases nor are these minerals regulated
by the Occupational Safety and Health Administration. Finally, there are a number
of other mineral species which can occur in human lung samples that satisfy the
definition for a fiber as given above. These similarly have not been associated
with asbestos-induced diseases. All of these various minerals satisfying the
definition for a fiber can be referred to as elongated mineral particles (EMP).
It is the purpose of this presentation to discuss the role of scanning electron
microscopy (SEM) equipped with an energy dispersive x-ray analyzer (EDXA) in the
detection and classification of EMP in human lung samples.
PMID- 29960000
TI - The asbestos-carbon nanotube analogy: An update.
AB - Nanotechnology is an emerging industry based on commercialization of materials
with one or more dimensions of 100 nm or less. Engineered nanomaterials are
currently incorporated into thin films, porous materials, liquid suspensions, or
filler/matrix nanocomposites with future applications predicted in energy and
catalysis, microelectronics, environmental sensing and remediation, and
nanomedicine. Carbon nanotubes are one-dimensional fibrous nanomaterials that
physically resemble asbestos fibers. Toxicologic studies in rodents demonstrated
that some types of carbon nanotubes can induce mesothelioma, and the World Health
Organization evaluated long, rigid multiwall carbon nanotubes as possibly
carcinogenic for humans in 2014. This review summarizes key physicochemical
similarities and differences between asbestos fibers and carbon nanotubes. The
"fiber pathogenicity paradigm" has been extended to include carbon nanotubes as
well as other high-aspect-ratio fibrous nanomaterials including metallic
nanowires. This paradigm identifies width, length, and biopersistence of high
aspect-ratio fibrous nanomaterials as critical determinants of lung disease,
including mesothelioma, following inhalation. Based on recent theoretical
modeling studies, a fourth factor, mechanical bending stiffness, will be
considered as predictive of potential carcinogenicity. Novel three-dimensional
lung tissue platforms provide an opportunity for in vitro screening of a wide
range of high aspect ratio fibrous nanomaterials for potential lung toxicity
prior to commercialization.
PMID- 29960001
TI - Flavonoids interfere with NLRP3 inflammasome activation.
AB - NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome is
a component of innate immunity, and is responsible for producing mature IL-1beta
and -18. Several flavonoids were found to affect inflammasome pathway, but the
mechanism of action is still obscure. To elucidate the effects on NLRP3
inflammasome pathway and to determine the structure-activity relationships, NLRP3
inflammasome in differentiated THP-1 cells was activated via treatment with
monosodium urate (MSU) crystals. Levels of mature IL-1beta, NLRP3 inflammasome
components and apoptosis-associated speck-like protein containing a CARD (caspase
recruitment domain) (ASC) oligomerization were investigated and the mechanisms of
action were also elucidated. Among the 56 flavonoids initially tested, only
flavone, 2',4'-dihhydroxyflavone, 3',4'-dichloroflavone, 4',5,7-trihydroxyflavone
(apigenin), 3,4',5,7-tetrahydroxyflavone (kaempferol) and 3,3',4',5,7
pentahydroxyflavone (quercetin) significantly inhibited IL-1beta production at 10
MUM. Apigenin, kaempferol and 3',4'-dichloroflavone inhibited ASC oligomerization
without affecting the ASC level in cell lysates. Apigenin also inhibited absent
in melanoma 2 (AIM2) inflammasome-related pathway, but not NLR family CARD domain
containing protein 4 (NLRC4) inflammasome activation. The action of apigenin on
NLRP3 inflammasome activation is mediated partly via inhibition of
phosphorylation of spleen tyrosine kinase/protein tyrosine kinase 2 (Syk/Pyk2)
pathway. Furthermore, orally administered apigenin (100 mg/kg) strongly reduced
the number of neutrophils and monocytes in MSU-induced peritonitis in mice. The
present study, for the first time, demonstrated the structure-activity profiles
of flavonoids in NLRP3 inflammasome activation and mechanisms of cellular action.
Certain flavonoids including apigenin are expected to ameliorate the inflammatory
symptoms in autoinflammatory diseases associated with NLRP3 inflammasome
activation.
PMID- 29960002
TI - Expression of cytochrome P450 epoxygenases and soluble epoxide hydrolase is
regulated by hypolipidemic drugs in dose-dependent manner.
AB - CYP epoxygenases metabolize arachidonic acid into four regioisomers of
epoxyeicosatrienoic acids (EETs) which are hydrolysed into their corresponding
diols by soluble epoxide hydrolase (sEH). EETs are very biologically active
molecules. They promote proliferation and inhibit apoptosis as well as numerous
other functions within organisms. Peroxisome proliferator-activated receptor
alpha (PPARalpha) play role in regulation of CYP epoxygenases and sEH. PPARalpha
is the ligand-dependent transcriptional factor which is activated by various
compounds, including fibrates. The latter are widely used in clinical practice.
This study investigates the changes in expression of CYP2C8, CYP2J2, and sEH in
HEK293, HepG2, and HT-29 cell lines after fibrate treatment using two different
incubation times. The results demonstrate that the effect of fibrates on
arachidonic acid-metabolizing enzymes expression is concentration-dependent.
Although CYP2C8 expression is downregulated by the fibrates treatment, the
results reveal that changes in CYP2J2/sEH ratio are closely associated with cell
proliferation and could explain the differing proliferation response of cells to
different concentrations of fibrates.
PMID- 29960003
TI - Reevaluating Warm Ischemia Time as a Predictor of Renal Function Outcomes After
Robotic Partial Nephrectomy.
AB - OBJECTIVE: To explore whether variation of warm ischemia time (WIT) is associated
with functional and perioperative outcomes following robotic partial nephrectomy
(RPN). MATERIALS AND METHODS: Six hundred sixty eight patients, each with 2
kidneys, undergoing RPNs for a cT1 tumor were identified from a U.S. multi
institutional database. The associations between WIT, normal excisional volume
loss (EVL), and surgical and renal function outcomes, including acute kidney
injury at discharge and percent change in eGFR at up to 24 months post-RPN, were
evaluated using Spearman's rank correlation test as well as multivariable models
controlling for tumor, surgeon, and patient characteristics. RESULTS: WIT was
weakly correlated with EVL (r = 0.32, P < .001), blood loss (r = 0.34, P < .001),
and length of stay (r = 0.35, P < .001). WIT was found to be significantly
associated with acute kidney injury at discharge (odds ratio = 6.23; confidence
interval 1.52, 30.39). Extended WIT was not found to be significantly associated
with renal function decline at 1 year post RPN (P > .05). CONCLUSION: Extended
WIT is associated with worse perioperative outcomes. While controlling for tumor
size and EVL, effects on short-term renal function were still seen after as short
as 20 minutes. Efforts to limit warm ischemia time should continue to be
implemented during RPN to maximize postoperative renal function.
PMID- 29960004
TI - A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for
Postfinasteride Syndrome.
AB - OBJECTIVE: To quantify reports made to the Food and Drug Administration Adverse
Event Reporting System (FAERS), create a demographic of patient reports, and
examine the cluster of symptoms to correlate consistency of postfinasteride
syndrome (PFS) complaints. PFS is a provisional diagnosis encompassing a cluster
of sexual, physical, and psychological and/or neurologic symptoms associated with
5-alpha reductase inhibitor use that emerge or continue after discontinuation of
medication. MATERIALS AND METHODS: FAERS dataset of 5-alpha reductase inhibitors
from April 2011 to October 2014 was obtained. Each FAERS report had 16 categories
for completion, but not every report was fully completed. Statistical analysis
compared variables of interest between the 2 doses of finasteride (1 mg vs 5 mg).
RESULTS: From FAERS, 2048 monotherapy cases were identified: 1581 of finasteride
1 mg, 240 of finasteride 5 mg, and 226 of unreported doses. Possibly related to
labeling changes, from 2011 to 2014, there was a significant increase in adverse
events (AEs) reported involving 1 mg dosing. Finasteride use was reported with
many sexual AEs including diminished libido, erectile dysfunction, and
ejaculatory complaints. Other common AEs included dermatologic, metabolic, and
psychological and/or neurologic complaints. There were more AE reports with the 1
mg dose than the 5 mg dose. One case of dutasteride reported back pain, not
generally attributed to PFS. CONCLUSION: FAERS data suggests that finasteride
exposure is reported with a diverse collection of symptoms, particularly in
younger men on 1 mg dosage compared to older men on 5 mg. Many of these
complaints fall well out of the realm of previously established AEs from long
term controlled studies.
PMID- 29960005
TI - Patient-specific Virtual Simulation-A State of the Art Approach to Teach Renal
Tumor Localization.
AB - OBJECTIVE: To test whether a novel visuospatial testing platform improves trainee
ability to convert two-dimensional to three-dimensional (3D) space. METHODS:
Medical students were recruited from Baylor College of Medicine and McGovern
Medical School (Houston, TX). We 3D reconstructed 3 partial nephrectomy cases
using a novel, rapid, and highly accurate edge-detection algorithm. Patient
specific reconstructions were imported into the dV-Trainer (Mimics Technologies,
Seattle, WA) as well as used to generate custom 3D printed physical models. Tumor
location was altered digitally to generate 9 physical models for each case, 1
with the correct tumor location and 8 with sham locations. Subjects were
randomized 1:1 into the dV-Trainer (intervention) and No-dV-Trainer (control)
groups. Each subject completed the following steps: (1) visualization of computed
tomographic images, (2) visualization of the reconstructed kidney and tumor in
the dV-Trainer (intervention group only), and (3) selection of the correct tumor
location on the 3D printed models (primary outcome). Normalized distances from
the correct tumor location were quantified and compared between groups. RESULTS:
A total of 100 subjects were randomized for this study. dV-Trainer use
significantly improved subjects ability to localize tumor position (tumor
localization score: 0.24 vs 0.38, P < .001). However, subjects in the No-dV
Trainer group more accurately assigned R.E.N.A.L. scores. CONCLUSION: Even brief
exposure to interactive patient-specific renal tumor models improves a novice's
ability to localize tumor location. Virtual reality simulation prior to surgery
could benefit trainees learning to localize renal masses for minimally invasive
partial nephrectomy.
PMID- 29960006
TI - Are methicillin-susceptible Staphylococcus aureus carriers protected from
methicillin-resistant Staphylococcus aureus infections?
PMID- 29960007
TI - Colistin resistance in carbapenemase-producing Klebsiella pneumoniae bloodstream
isolates: Evolution over 15 years and temporal association with colistin use by
time series analysis.
AB - Colistin is often the only available treatment option against infections caused
by carbapenemase-producing Klebsiella pneumoniae (CP-Kp). In this study, the
evolution of colistin resistance among CP-Kp and its relationship with colistin
use in a tertiary-care hospital in Athens, Greece, was investigated. All CP-Kp
blood isolates recovered between January 2002 and June 2016 were tested for
susceptibility to colistin by agar dilution and broth microdilution methods. Data
on colistin use were collected from the pharmacy database. Time series of
colistin use and resistance were analysed using the Box and Jenkins method. A
transfer function model was built to quantify the dynamic relationship between
colistin use and resistance. Overall, 313 CP-Kp isolates were identified. The
percentage colistin resistance increased from 0% in 2002 to 26.9% in 2016 (R2 =
0.5, P < 0.01). A temporal association between colistin use and resistance was
observed; an increase in colistin use by 1 DDD/100 patient-days led to a 0.05
increase in the incidence rate of colistin resistance. The time lag between the
effect of colistin use on subsequent variations in colistin resistance was 3
months. Colistin use and prior levels of colistin resistance could explain 69% of
colistin resistance; in the remaining 31%, other factors might have played a
role. The results presented here demonstrate a significant temporal association
between colistin use and colistin resistance. These findings have important
implications in implementing strategies to contain colistin resistance.
PMID- 29960008
TI - Integrons and insertion sequence common region 1 (ISCR1) of carbapenem-non
susceptible Gram-negative bacilli in fecal specimens from 5000 patients in
southern China.
AB - The integrons and insertion sequence common region 1 (ISCR1) of 329 carbapenem
non-susceptible Gram-negative bacilli, excluding 60 Stenotrophomonas maltophilia
strains, in fecal specimens from 5000 patients in southern China were studied. A
total of 205 (62.3%) class 1 integron-positive strains and 126 (61.5%) gene
cassette-positive strains were detected, and 44 types of gene-cassette arrays
were found, including 8 types described for the first time in the corresponding
species and one gene cassette originally detected in integrons, a putative
helicase. A total of 9 types of 21 ISCR1-linked resistance gene regions in 35
ISCR1-positive bacilli and 2 previously unreported types of complex class 1
integrons were detected. All strains were extensively drug-resistant. Class 1
integrons and ISCR1 were widely disseminated and these structures carried various
resistance genes, which were closely associated with mechanisms of multidrug
resistance, including carbapenem resistance.
PMID- 29960009
TI - Transcriptional effects of androstenedione and 17alpha-hydroxyprogesterone in
zebrafish embryos.
AB - Steroid hormones in the aquatic environment may pose a risk to fish health. Here
we evaluated effects of two different class steroids that frequently occur in the
aquatic environment, the androgen androstenedione (A4) and the progestin 17alpha
hydroxyprogesterone (17-OHP4). Zebrafish embryos were exposed to four
concentrations of A4 and the positive control testosterone and to 17-OHP4, and
transcriptional changes were determined at 96 h post fertilization (hpf) and 120
hpf. Transcriptional changes of 18 selected genes were assessed upon exposure to
measured concentrations of 0.004, 0.046, 0.62 and 6.56 MUg/L A4. Significant
induction of the genes encoding sulfotransferase (sult2st3) and aromatase
(cyp19b) occurred in 120 hpf embryos at 6.56 MUg/L A4 and 1 MUg/L testosterone.
Additionally, cyp2k7 was significantly induced in two of three independent
experiments. 17-OHP4 did not induce physiological effects (muscle contraction,
heart rate, hatching success, swimming activity) at concentrations between 0.01
and 10 MUg/L. Of the analyzed 15 genes, slight transcriptional alterations
occurred for the genes encoding progesterone receptor, aromatases (cyp19a) and
(cyp19b) and cyp2k7 at 10 MUg/L. Our study highlights sult2st3, cyp19b and cyp2k7
as potential markers of androgen exposure in fish and indicates that 17-OHP4 is
not likely to pose a risk for fish at environmental concentrations.
PMID- 29960010
TI - Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel
normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug
resistance in EGFR-mutated non-small cell lung cancer.
AB - : Although novel molecular targeted drugs have been recognized as an effective
therapy for non-small cell lung cancer (NSCLC) harboring epidermal growth factor
receptor (EGFR) activating mutations, their efficacy fails to meet the
expectation due to the acquired resistance in tumors. Up-regulation of the anti
apoptotic protein Survivin was shown to contribute to the resistance to EGFR
tyrosine kinase inhibitors (TKI) in EGFR mutation-positive NSCLC. However, the
unorganized tumor blood vessels impeded drug penetration into tumor tissue. The
resulting insufficient intracellular drug/gene delivery in drug-resistant cancer
cells remarkably weakened the drug efficacy in NSCLC. In this work, a multi
functional drug delivery system AP/ES was developed by using anti-EGFR aptamer
(Apt)-modified polyamidoamine to co-deliver erlotinib and Survivin-shRNA.
Chloroquine (CQ) was used in combination with AP/ES to normalize tumor vessels
for sufficient drug/gene delivery to overcome drug resistance in NSCLC cells. The
obtained AP/ES possessed desired physicochemical properties, good biostability,
controlled drug release profiles, and strong selectivity to EGFR-mutated NSCLC
mediated by Apt. CQ not only enhanced endosomal escape ability of AP/ES for
efficient gene transfection to inhibit Survivin, but also showed strong vessel
normalization ability to improve tumor microcirculation, which further promoted
drug delivery and enhanced drug efficacy in erlotinib-resistant NSCLC cells. Our
innovative gene/drug co-delivery system in combination with CQ showed a promising
outcome in fighting against erlotinib resistance both in vitro and in vivo. This
work indicates that normalization of tumor vessels could help intracellular
erlotinib/Survivin-shRNA delivery and the down-regulation of Survivin could act
synergistically with erlotinib for reversal of erlotinib resistance in EGFR
mutation-positive NSCLC. STATEMENT OF SIGNIFICANCE: NSCLC patients who benefited
from EGFR-TKIs inevitably developed acquired resistance. Previous research
focused on synthesis of new generation of molecular targeted drugs that could
irreversibly inhibit EGFR with a particular gene mutation to overcome drug
resistance. However, they failed to inhibit EGFR with other gene mutations.
Activation of bypass signaling pathway and the changes of tumor microenvironment
are identified as two of the mechanisms of acquired resistance to EGFR-TKIs. We
therefore constructed multifunctional gene/drug co-delivery nanocomplexes AP/ES
co-formulated with chloroquine that could target the both two mechanisms. We
found that chloroquine not only enhanced endosomal escape ability of AP/ES for
efficient gene transfection to inhibit Survivin, but also showed strong vessel
normalization ability to improve tumor microcirculation, which further promoted
drug delivery into tumor tissue and enhanced drug efficacy in erlotinib-resistant
NSCLC.
PMID- 29960011
TI - Single-cell epigenetics - Chromatin modification atlas unveiled by mass
cytometry.
AB - Modifications of histone proteins are fundamental to the regulation of epigenetic
phenotypes. Dysregulations of histone modifications have been linked to the
pathogenesis of diverse human diseases. However, identifying differential histone
modifications in patients with immune-mediated diseases has been challenging, in
part due to the lack of a powerful analytic platform to study histone
modifications in the complex human immune system. We recently developed a highly
multiplexed platform, Epigenetic landscape profiling using cytometry by Time-Of
Flight (EpiTOF), to analyze the global levels of a broad array of histone
modifications in single cells using mass cytometry. In this review, we summarize
the development of EpiTOF and discuss its potential applications in biomedical
research. We anticipate that this platform will provide new insights into the
roles of epigenetic regulation in hematopoiesis, immune cell functions, and
immune system aging, and reveal aberrant epigenetic patterns associated with
immune-mediated diseases.
PMID- 29960012
TI - Management of patients with sickle cell disease in oral surgery. Literature
review and update.
AB - Sickle cell disease, the most common genetic disease in the world, is a chronic
hemolytic disease that can be complicated by severe vaso-occlusive pain crises
resulting in tissue necrosis and even death. Due to its increasing incidence,
oral surgeons will inevitably be faced with the management of these patients. To
limit the risk of crises, our goal is to share recommendations for the management
of sickle cell patients in oral surgery. The vaso-occlusive crises (VOC), heart
attacks and chronic anemia endured by these patients cause chronic lesions in
various organs. Complications include retinal disease, avascular necrosis,
priapism, neurological involvement (cerebrovascular accident), cardiomyopathy,
lower limb ulceration, renal and hepatic dysfunction, and cardiopulmonary
disease. These complications inevitably lead to an increase in mortality rate.
Thorough knowledge of this pathology is essential for the management of these
patients in oral surgery. Management strategies include prevention and diagnosis
of oral lesions related to sickle cell disease and its treatment, as well as
methods of preparation and execution of oral surgery procedures. We suggest
guidelines for the management of these complications and implementation of
preoperative, intraoperative and postoperative surgical protocols for both
practitioners and patients.
PMID- 29960013
TI - Development of the jaw sensorimotor control and chewing - a systematic review.
AB - Mastication is a complex sensorimotor interaction between the central nervous
system and the peripheral masticatory apparatus. To understand the effect of oro
facial abnormalities on mastication, it is important to first understand the
normal development of jaw sensorimotor control and chewing in healthy children.
Original studies which investigated four main objective parameters of chewing,
i.e. maximum occlusal bite force, electromyography (EMG), jaw kinematics and
chewing efficiency in children were systematically searched using three
established databases. The targeted sample was healthy children below the age of
18-years. All studies that subjectively assessed mastication, studies of children
with abnormalities, or non-English studies were excluded. A total of 6193 papers
were identified, 53 met the final inclusion criteria. Results are presented
according to the dentition stage. Children below 6-years (primary dentition) had
lower biting forces and EMG activity, and the frontal jaw movement pattern was
more laterally displaced and less stable than children older than 6-years. EMG
activities and bite forces increased in children 6- to 10-year-old (early mixed
dentition) with a reduction in lateral jaw displacement and an increase in
vertical jaw displacement. Twelve-year-old children were able to chew food into
smaller particles compared to 6-year-olds. Gender differences were visible in all
parameters except EMG activity in late mixed dentition (10- to 12-years). After
12-years, there was a significant increase in bite forces and EMG activities, and
the frontal jaw pattern became similar to adults. Studied chewing parameters
gradually improve with the development of the oro-facial structures and were
mainly influenced by dental eruption. A significant development of chewing
parameters occurs after 12 years of age. A transition to the adult-type of
masticatory behavior occurs between 10- to 14-years of age.
PMID- 29960014
TI - Chronic depression symptoms desensitize renin activity to protect against volume
loading hypertension in Blacks: The SABPA study.
AB - BACKGROUND: Low-renin levels in Blacks have been associated with volume-loading
hypertension (HT). Depression symptoms, frequently co-occurring with vascular
dysregulation, might reflect a disturbed renin-angiotensin-aldosterone-system
(RAAS). We aimed to assess prospective changes (?) in depression symptoms, RAAS
(renin, aldosterone), diastolic blood pressure (DBP), and estimated glomerular
filtration rate (eGFR) in a bi-ethnic sex cohort. METHODS: We included 195 Black
and White teachers (43.7 +/- 9 years) from a South African 3-year prospective
study. Hypertension medication users, diabetics and human immunodeficiency virus
infected individuals were excluded. Depression symptoms (Patient-Health
Questionnaire-9/PHQ-9), 24 h blood pressure measurements and fasting blood
samples were obtained. RESULTS: Blacks had lower renin but higher DBP and eGFR
levels at baseline (p <= .01) when compared to Whites. Blacks and Whites with
depression (PHQ-9 >= 10) at baseline developed co-morbidity for having both
depression plus DBP-HT at follow-up (Blacks, 49.1%; Whites, 13.1%). At 3-year
follow-up, chronic depression symptoms were related to chronic lower renin in
Blacks [Adjusted R2 0.20; beta -0.37 (-0.66, -0.08), p = .02]. Chronic depression
symptoms also predicted DBP hypertension in Blacks [ROC AUC = 0.61 (0.48-0.75);
sensitivity/specificity 78.1/46.3%]. No prospective associations existed between
depression symptoms, aldosterone and eGFR. CONCLUSION: Chronic depression
symptoms in Blacks activated the RAAS system activity with apparent
desensitization of renin activity. Chronic depression could be causal to
hypertension and in turn, lowers renin activity as a protective mechanism against
volume-loading. These findings emphasize the potential impact of depression on
the low renin-hypertension phenotype in Blacks in terms of diagnosis and
treatment.
PMID- 29960015
TI - A doxorubicin loaded colloidal delivery system for the intravesical therapy of
non-muscle invasive bladder cancer using wheat germ agglutinin as targeter.
AB - Non-muscle invasive bladder cancer is one of the most frequent forms of cancer.
Commonly, the superficial tumor is removed by a minimal invasive surgery, mostly
followed by the intravesical instillation of cytostatic agents. Although the
initial treatment is usually successful, the recurrence rate is extraordinary
high, which might be grounded in limiting factors during instillation, such as
the high resistance of the bladder wall and the constant dilution with the
permanently produced urine reducing the probability of interaction between the
drug and the target cell. To overcome these limitations, we introduce a lectin
mediated drug delivery system consisting of wheat germ agglutinin as targeter,
poly-l-glutamic acid as backbone and the active pharmaceutical ingredient (API)
doxorubicin that should prolong the residence time in the bladder cavity. The
optimized WGA-PGA-Doxo conjugate revealed an API load of 81 molecules per mole
backbone and convinced in urothelial cell monolayer studies with an up to 56-fold
higher cell-binding potential than pure doxorubicin. Additionally, the highly
substituted drug delivery system not only internalized into urothelial cells, but
also inhibited cell viability up to 99%. The combination of the high drug load
with the promising cell-associative properties, which also revealed a higher
affinity to malignant than to healthy urothelial cells, and the proven cytotoxic
potential might lead to an improved efficacy of intravesical chemotherapy.
PMID- 29960016
TI - Surface modification with polyethylene glycol enhances colorectal distribution
and retention of nanoparticles.
AB - Dense surface modification with short chain polyethylene glycol (PEG) has been
previously demonstrated as favoring the transport of nanoparticles (NPs) across
mucus. However, the ability of such approach to influence the distribution and
retention of NPs along the length of the colorectum after rectal delivery has not
been previously established. Herein, the distribution and retention of
poly(lactic-co-glycolic acid) NPs modified with PEG in a non-covalent fashion are
reckoned in a mouse model. Despite overall rapid depletion, both PEG-modified and
non-modified NPs are able to reach the middle segment of the colon. PEG-modified
NPs are able to enhance retention up to at least two hours post-administration,
contrasting with nearly residual levels observed for non-modified NPs after 15
min. The ability of PEG-modified NPs to putatively cross mucus also appears to
promote association with tissues. Overall, the work provides significant insights
as to the behavior of NPs in the colorectum, which could be valuable for the
development of rectal nanomedicines. It further reinforces the potential
usefulness of PEG-modified NPs as mucus-penetrating carriers for mucosal drug
delivery.
PMID- 29960017
TI - Does botulinum toxin treatment improve upper limb active function?
AB - BACKGROUND: Spasticity following lesions of the central nervous system such as
stroke is a major cause of impairment and disability, especially when it affects
the upper limb, and can be focally relieved by intramuscular injections of
botulinum toxin (BT). Functional improvements of the affected upper limb after a
BT focal treatment remain controversial. OBJECTIVE: We aimed to assess the
functional effects of BT treatment on upper-limb spasticity in the literature,
identify flaws and deficiencies in proving these effects and propose leads for
future trials. METHODS: We searched the MEDLINE and Cochrane databases for
trials, reviews and meta-analyses assessing the effect of BT injection in upper
limb spasticity. This was a non-systematic narrative review, and the selection of
articles was based on the authors' expertise. The review focused on stroke
related spasticity and disability. RESULTS: Patients' therapeutic targets
involved use of the disability assessment scale (DAS) or goal attainment scale
(GAS). Impairments and passive function goals prevailed for active function and
participation and were more frequently achieved for the former than the latter.
Meta-analyses showed no to mild effect sizes for improvement in upper-limb
function but failed to show higher and/or better use of the paretic upper limb in
activities of daily living after BT injection. CONCLUSION: BT injections for
impairment and passive function are related to improved kinematic parameters;
however, the relation between relief of spasticity and improved upper-limb
activity has not been established. Possible explanations for the lack of
functional effect in studies are first, disability is mainly due to muscle
weakness rather than spasticity, so patients with the best underlying motricity
may benefit the most from BT injections; second, assessment methods may not be
adapted to screen eligible patients; third, most studies' endpoints were at 4 to
12 weeks after a single injection, but repeated treatment sessions might be
needed to observe functional outcome on the upper limbs; and finally, the
association of rehabilitation programs or non-pharmacological treatments may
enhance the functional effects of BT injections.
PMID- 29960018
TI - Mechanism of cyclosporine A nephrotoxicity: Oxidative stress, autophagy, and
signalings.
AB - Cyclosporine A (CsA) is a widely used immunosuppressive agent that greatly
reduces the rates of kidney-, heart-, and liver-transplant rejection. However,
CsA nephrotoxicity is a serious side effect that limits the clinical use of CsA.
While the mechanisms underlying CsA nephrotoxicity are still not fully
understood, increasing lines of evidence suggest that oxidative stress plays an
important role in this phenomenon. Specifically, CsA induces endoplasmic
reticulum stress and increases mitochondrial reactive oxygen species production:
this modifies the redox balance, which causes lipid peroxidation and thereby
induces nephrotoxicity. Recent studies on the pathogenesis of CsA nephrotoxicity
suggest that CsA-induced autophagy can alleviate the deleterious effects of CsA
induced endoplasmic reticulum stress, thereby preventing nephrotoxicant-induced
renal injury. A variety of signaling pathways participate in the pathogenesis of
CsA nephrotoxicity. Specifically, the p38, ERK, and JNK MAPK subfamilies are all
involved in CsA nephrotoxicity, while NF-kappaB is a target molecule of CsA.
Moreover, the fibrogenic cytokine TGF-beta1 contributes to CsA-induced renal
fibrosis, while Nrf2 modulates CsA-induced cellular oxidative stress. In
addition, CsA generally inhibits nitric oxide synthesis and impairs endothelium
dependent relaxation in the renal artery. However, some reports also suggest that
nitric oxide synthesis is enhanced in the kidney cortex during CsA
nephrotoxicity. Notably, the biomarkers of CsA nephrotoxicity associated with CsA
have not been reviewed previously. Therefore, in this review, we will first
provide an update on CsA nephrotoxicity in humans and describe the potential
biomarkers of CsA nephrotoxicity. The molecular and cellular mechanisms that
underlie CsA nephrotoxicity and the roles played by oxidative stress, autophagy,
and signaling pathways will then be comprehensively summarized and discussed.
Finally, the current therapeutical strategies for CsA nephrotoxcixity are
summarized. We hope this review will provide a better understanding of CsA
nephrotoxicity, thereby improving the management of patients who are treated with
CsA.
PMID- 29960019
TI - Nano-diamino-tetrac (NDAT) inhibits PD-L1 expression which is essential for
proliferation in oral cancer cells.
AB - Programmed death-ligand 1 (PD-L1) is a critical regulator to defend tumor cells
against immune surveillance. Thyroid hormone has been shown to induce PD-L1
expression in cancer cells. Its nano-particulated analogue, nano-diamino-tetrac
(NDAT; Nanotetrac) is an anticancer/anti-angiogenic agent. In the current study,
the inhibitory mechanism by which NDAT inhibited PD-L1 mRNA abundance and PD-L1
protein content in oral cancer cells was investigated. NDAT inhibited inducible
PD-L1 expression and protein accumulation by the inhibition of activated ERK1/2
and PI3K. Knockdown PD-L1 also inhibited the proliferation of oral cancer cells
which suggests that the inhibitory effect of NDAT on PD-L1 expression maybe is
one of the critical mechanisms for NDAT-induced anti-proliferative effect in oral
cancer cells.
PMID- 29960020
TI - Anti-proliferative activity-guided isolation of clerodermic acid from Salvia
nemorosa L.: Geno/cytotoxicity and hypoxia-mediated mechanism of action.
AB - The adaptation of solid tumors to the low oxygen/nutrient environment is mediated
by the pivotal transcription role of hypoxia-inducible factor-1 (HIF-1). Thus,
the HIF-1 and its subunits have been considered to be hopeful anti-cancer
targets. Various natural compounds were reported to persuade cell cytotoxicity
through targeting and downregulation of the HIF-1. The genus Salvia is a rich
source of bioactive terpenoids which show promising anti-cancer activities. Here,
the identification of natural anti-proliferative compound targeting the HIF
1alpha expression was reported. A bioassay-guided isolation was employed for the
discovery of natural anti-proliferative compounds from Salvia extracts using MTT
assay against A549 cells. In this direction, clerodermic acid (CDA) as a potent
cytotoxic compound was purified from Salvia nemorosa and identified using 1D and
2D NMR analysis. Results indicated that CDA has anti-proliferation activity (IC50
value of 35 MUg/mL) which was confirmed by genotoxicity and apoptosis detection
analyses. The quantitative qPCR analysis showed that the expression level of HIF
1 alpha was strongly inhibited in the hypoxic cells treated with CDA compared to
the untreated cells tolerated hypoxia. Findings exhibited that S. nemorosa and
clerodermic acid have significant potential for reducing HIF-1alpha expression
and could be considered for further studies for cancer therapy.
PMID- 29960021
TI - Appropriateness of End-of-Life Care in People Dying From COPD. Applying Quality
Indicators on Linked Administrative Databases.
AB - CONTEXT: Large-scale evaluations of the quality of end-of-life care in people
with chronic obstructive pulmonary disease (COPD) are lacking. OBJECTIVES: By
means of a validated set of quality indicators (QIs), this study aimed to 1)
assess appropriateness of end-of-life care in people dying from COPD; 2) examine
variation between care regions; 3) establish performance standards. METHODS: We
conducted a retrospective observational study of all deaths from COPD (ICD-10
codes J41-J44) in 2012 in Belgium, using data from administrative population
level databases. QI scores were risk-adjusted for comparison between care
regions. RESULTS: A total of 4231 people died from COPD. During the last 30 days
of life, 60% was admitted to hospital and 11.8% received specialized palliative
care. Large regional variation was found in specialized palliative care use (4.0%
32.0%) and diagnostic testing in the last 30 days of life (44.0%-69.7%). Based on
best performing quartile scores, relative standards were set (e.g., <=54.9% for
diagnostic testing). CONCLUSION: Our study found indications of inappropriate end
of-life care in people with COPD, such as high percentages of diagnostic testing
and hospital admissions and low proportions receiving specialized palliative
care. Risk-adjusted variation between regions was high for several QIs,
indicating the usefulness of relative performance standards to improve quality of
end-of-life COPD care.
PMID- 29960022
TI - Production from both wild harvest and cultivation: The cross-border Swertia
chirayita (Gentianaceae) trade.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Swertia chirayita is the most widely traded
species in a genus of 150 species, many of which are used in traditional
medicine. S. chirayita is used mainly in Ayurvedic and Tibetan systems of
medicine and the homoeopathic system of medicine as well as in regional folk
medicine. Primarily wild collected, with some cultivation. S. chirayita is traded
as a medicinal substance and exported in the forms of dried whole plant or
extract of whole plant individually and/or as active ingredients of Ayurvedic
medicines. S. chirayita export valuations continue to make S. chirayita one of
Nepal's highest foreign exchange earning medicinal plant species. AIMS OF THE
REVIEW: The aims of this review were first, to assess the scale of the global
trade in S. chirayita, second, to review evidence from plant population biology
and from studies on the impacts of wild harvest on S. chirayita populations and
cultivation as an alternative source of supply. METHODS: The taxonomy and trade
names for S. chirayita were reviewed, followed by a synthesis of published
information on Swertia population biology and studies on impacts of wild S.
chirayita harvest from across the geographic range of this species. Data on the
prices paid for S. chirayita were then compiled for the period 2001-2017,
followed by an analysis of global trade data for S. chirayita. RESULTS AND
CONCLUSIONS: Based on India import data and assuming an estimate in an earlier
study that 60% of Nepal's S. chirayita production goes to India and 35% to Tibet,
then Nepal's 2013 annual production was about 711 metric tonnes (MT) of which
about 675.6 MT would be exported (India + Tibet). Nepal's 2014 annual production
would be an estimated 503.25 MT of which about 478 MT would be exported. Declines
in S. chirayita populations have been widely noted across its range. In India,
since 2004, a ban was placed on the export of wild harvested S. chirayita by the
Government of India, where the Director General of Foreign Trade prohibited
export of S. chirayita plants, plant portions and their derivatives and extracts
obtained from the wild with the exception of 'formulations'. Cultivation of S.
chirayita to meet commercial demand has been an important part of a solution to
over-exploitation of wild stocks in eastern Nepal for 25 years, producing
significant quantities that enter the export trade to India and Tibet. In
Sankhuwasabha district, for example, 53.1 MT of S. chirayita were produced in
2013/014, just over half of which (27 MT) were exported to India, with the
remainder exported to Tibet. Based on value-chain analysis and cost-benefit
assessments, S. chirayita cultivation has been shown to be profitable in Nepal.
However, since the first cost-benefit assessment was done (2013), prices dropped
from NRs750/kg in April 2013 to a low of 250 NRs/kg in December 2017). Taking
inflation into account further highlights the steep decline in the profitability
for local farmers, who have limited options for value-adding. Consequently,
farmers prefer to grow more profitable alternative crops, such as Nepal cardamom
(Amomum subulatum Roxb.).
PMID- 29960023
TI - Sphenodesme involucrata var. paniculata (C.B. Clarke) Munir.: Chemical
characterization, anti-nociceptive and anti-inflammatory activities of methanol
extract of leaves.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sphenodesme involucrata var. paniculata (C. B.
Clarke) Munir is native as well as endemic to South India. Its leaves are used in
folklore medicine to treat pain and rheumatism. OBJECTIVE: This study was aimed
to investigate the chemical characterization, anti-nociceptive and mode of action
underlying the anti-inflammatory effects of methanol extract of S. involucrata
leaves (MESi). METHODS: Phytoconstituents of MESi was analyzed using colorimetric
and liquid chromatography-mass spectrometry (LC-MS) methods, and the oral acute
toxicity was evaluated in mice up to 2000 mg/kg. The anti-nociceptive effect was
evaluated in hot plate and writhing tests; whereas the anti-inflammatory effect
was investigated using carrageenan, cotton pellet and lipopolysaccharide (LPS)
induced peritonitis models at doses of 100, 200 and 400 mg/kg. Additionally
nitric oxide (NO) and inflammatory cytokines levels were also evaluated. RESULTS:
MESi exhibited the high content of phenolics and flavonoids as well as compounds
like austricine, benzylglucosinolate, gossypin, justicidin B and cirsimarin were
detected in LC-MS. In the acute toxicity study, oral administration of MESi did
not cause any toxic effect and mortality up to 2000 mg/kg body weight in mice. In
the anti-nociceptive tests, MESi augmented the latency period at higher dose (400
mg/kg), on the other hand attenuated writhings at the dose of 400 mg/kg by 87.87%
(p < 0.001). In the carrageenan induced paw oedema MESi significantly inhibited
the oedema formation at dose 400 mg/kg by 32.1%; besides, anti-inflammatory
effect was registered in the cotton pellets-induced inflammation model at doses
200 and 400 mg/kg by 27.09% (p < 0.001) and 35.47% (p < 0.001) respectively. On
the other hand, MESi appreciably reduced leukocyte, neutrophils infiltration,
nitric oxide, TNF-alpha and IL-1beta levels and increased the IL-10 level in the
(LPS)-induced peritonitis model. CONCLUSION: The results conclude that MESi has
no acute toxic effect and it demonstrated potent anti-nociceptive and anti
inflammatory activities. Its anti-nociceptive activities are probably mediated
through peripheral and central mechanisms. The anti-inflammatory effect of MESi
involved the inhibition of neutrophils migration and the modulation of Th1 and
Th2 cytokines, besides the attenuation of production of PGE2 and NO. LC-MS
analysis revealed the predominant presence of the austricine,
benzylglucosinolate, gossypin, justicidin B and cirsimarin compounds, which are
possibly involved in the anti-nociceptive and anti-inflammatory effects of MESi.
The current study provided supportive evidence for the folklore use of S.
involucrata in the treatment of pain and inflammatory conditions.
PMID- 29960024
TI - Solid-State Insight Into the Action of a Pharmaceutical Solvate: Structural,
Thermal, and Dissolution Analysis of Indinavir Sulfate Ethanolate.
AB - The crystal structure of indinavir sulfate, a pharmaceutical administered as an
ethanol solvate, is presented, revealing a unique channel/ionic solvate structure
to be characteristic of the compound. The properties of the material with regard
to thermal treatment and water adsorption follow closely from the structure. The
in situ amorphization of the pharmaceutical upon contacting liquid water is
observed and highlights the unique dissolution enhancement of marketing the
crystalline solvate dosage. Through survey of published crystal structures, an
ambiguous sulfate/bisulfate ionization state is also observed in the crystal,
which challenges the general understanding of the pharmaceutical. This study
provides a solid-state insight into the function of a special multicomponent
crystalline pharmaceutical form.
PMID- 29960025
TI - Liquid Droplet of Protein-Polyelectrolyte Complex for High-Concentration
Formulations.
AB - The formulation of high-concentration protein solutions is a challenging issue
for achieving subcutaneous administration. Previously, we developed a method of
precipitation-redissolution using polyelectrolyte as a precipitant to produce
protein solutions at high concentrations. However, the redissolution yield of
proteins was insufficient. This study aims to optimize the solution conditions
for practical applications by combining IgG and poly-l-(glutamic acid) (polyE). A
systematic analysis of solution pH and polyE size conditions revealed that an
acidic condition favors precipitation, whereas neutral pH values are more
effective for the redissolution. We find that the optimal size for polyE ranged
from 15,000 to 50,000. This slight modification in the procedure in comparison
with previous studies increased the precipitation and redissolution yields to
nearly 100%, without irreversible protein denaturation. The fully reversible IgG
polyE complex formed as a droplet structure, which is similar to a condensate of
liquid-liquid phase separation. The droplet structure plays an indispensable role
in the salt-induced, redissolved state, which is pertinent to the new application
that takes advantage of the methods to produce highly concentrated protein
solutions.
PMID- 29960026
TI - N-7-Guanine Adduct of the Active Monoepoxide of Prodrug Treosulfan: First
Synthesis, Characterization, and Decomposition Profile Under Physiological
Conditions.
AB - (2S,3S)-1,2:3,4-diepoxybutane (DEB) cross-links DNA guanines by forming the
intermediate epoxy-adduct ((2'S,3'S)-N-7-(3',4'-epoxy-2'-hydroxybut-1'-yl)guanine
[EHBG]). This process is presently considered a primary mechanism for the action
of treosulfan (TREO), the prodrug that transforms to DEB via the monoepoxide
intermediate (2S,3S)-1,2-epoxybutane-3,4-diol 4-methanesulfonate (EBDM). In this
article, the N-7-guanine adduct of EBDM ((2'S,3'S)-N-7-(2'3'-dihydroxy-4'
methylsulfonyloxybut-1'-yl)guanine [HMSBG]) was synthesized for the first time,
and its stability was investigated at physiological in vitro conditions. To
synthesize HMSBG, EBDM, formed in-situ from TREO, was treated with guanosine in
glacial acetic acid at 60 degrees C followed by ribose cleavage in 1 M HCl at 80
degrees C. HMSBG was stable during the synthesis, which showed that a beta
hydroxy group protects the sulfonate moiety against hydrolysis in acid
environment. At pH 7.2 and 37 degrees C, HMSBG exclusively underwent first-order
epoxidation to EHBG with a half-life of 5.0 h. EHBG further decomposed to
trihydroxybutyl-guanine, chlorodihydroxybutyl-guanine (major products),
phosphodihydroxy-guanine, and a structural isomer (minor products). The isomeric
derivative was identified as guanine with a fused 7-membered ring, which provided
a new insight into the EHBG stability. To conclude, the exclusive conversion of
HMSBG to EHBG indicates that EBDM might contribute to DNA cross-linking
independently from DEB and play a more important role in the TREO action than
expected before.
PMID- 29960027
TI - Within-subject test-retest reliability of the atlas-based cortical volume
measurement in the rat brain: A voxel-based morphometry study.
AB - BACKGROUND: Various neurological and psychological disorders are related to
cortical volume changes in specific brain regions, which can be measured in vivo
using structural magnetic resonance imaging (sMRI). There is an increasing
interest in MRI studies using rat models, especially in longitudinal studies of
brain disorders and pharmacologic interventions. However, morphometric changes
observed in sMRI are only meaningful if the measurements are reliable. To date, a
systematic evaluation of the test-retest reliability of the morphometric measures
in the rat brain is still lacking. NEW METHOD: We rigorously evaluated the test
retest reliability of morphometric measures derived from the voxel-based
morphometry (VBM) analysis. 37 Sprague-Dawley rats were scanned twice at an
interval of six hours and the gray matter volume was estimated using the VBM
DARTEL method. The intraclass coefficient, percent volume change and Pearson
correlation coefficient were used to evaluate the reliability in 96 subregions of
the rat brain. RESULTS: Most subregions showed excellent test-retest
reliabilities within an interval of 6 h while a few regions demonstrated lower
reliability, especially in the retrosplenial granular cortex. The results were
consistent between different methods of reliability assessment. COMPARISON WITH
EXISTING METHOD: To the best of our knowledge, this is the first study to
quantify the test-retest reliability of the VBM measurements of the rat brain.
CONCLUSION: Atlas-based cortical volume of the rat brain can be reliably
estimated using the VBM-DARTEL method in most subregions. However, findings in
subregions with lower reliability must be interpreted with caution.
PMID- 29960028
TI - Data-driven re-referencing of intracranial EEG based on independent component
analysis (ICA).
AB - BACKGROUND: Intracranial recordings from patients implanted with depth electrodes
are a valuable source of information in neuroscience. They allow for the unique
opportunity to record brain activity with high spatial and temporal resolution. A
common pre-processing choice in stereotactic EEG (S-EEG) is to re-reference the
data with a bipolar montage. In this, each channel is subtracted from its
neighbor, to reduce commonalities between channels and isolate activity that is
spatially confined. NEW METHOD: We challenge the assumption that bipolar
reference effectively performs this task. To extract local activity, the
distribution of the signal source of interest, interfering distant signals, and
noise need to be considered. Referencing schemes with fixed coefficients can
decrease the signal to noise ratio (SNR) of the data, they can lead to
mislocalization of activity and consequently to misinterpretation of results. We
propose to use Independent Component Analysis (ICA), to derive filter
coefficients that reflect the statistical dependencies of the data at hand.
RESULTS: We describe and demonstrate this on human S-EEG recordings. In a
simulation with real data, we quantitatively show that ICA outperforms the
bipolar referencing operation in sensitivity and importantly in specificity when
revealing local time series from the superposition of neighboring channels.
COMPARISON WITH EXISTING METHOD(S): We argue that ICA already performs the same
task that bipolar referencing pursues, namely undoing the linear superposition of
activity and will identify activity that is local. CONCLUSIONS: When
investigating local sources in human S-EEG, ICA should be preferred over re
referencing the data with a bipolar montage.
PMID- 29960029
TI - Establishment of a precise novel brain trauma model in a large animal based on
injury of the cerebral motor cortex.
AB - BACKGROUND: Animal models are essential in simulating clinical diseases and
facilitating relevant studies. NEW METHOD: We established a precise canine model
of traumatic brain injury (TBI) based on cerebral motor cortex injury which was
confirmed by neuroimaging, electrophysiology, and a series of motor function
assessment methods. Twelve beagles were divided into control, sham, and model
groups. The cerebral motor cortex was identified by diffusion tensor imaging
(DTI), a simple marker method, and intraoperative electrophysiological
measurement. Bony windows were designed by magnetic resonance imaging (MRI) scan
and DTI. During the operation, canines in the control group were under general
anesthesia. The canines were operated via bony window craniotomy and dura mater
opening in the sham group. After opening of the bony window and dura mater, the
motor cortex was impacted by a modified electronic cortical contusion impactor
(eCCI) in the model group. RESULTS: Postoperative measurements revealed damage to
the cerebral motor cortex and functional defects. Comparisons between
preoperative and postoperative results demonstrated that the established model
was successful. COMPARISON WITH EXISTING METHOD(S): Compared with conventional
models, this is the first brain trauma model in large animal that was constructed
based on injury to the cerebral motor cortex under the guidance of DTI, a simple
marker method, and electrophysiology. CONCLUSION: The method used to establish
this model can be standardized to enhance reproducibility and provide a stable
and precise large animal model of TBI for clinical and basic research.
PMID- 29960030
TI - The extended application of The Rat Brain in Stereotaxic Coordinates in rats of
various body weight.
AB - BACKGROUND: Stereotaxic procedures in rats are frequently used in neurological
research. The commonly used rat brain stereotaxic atlases areThe Rat Brain in
Stereotaxic Coordinates, the second most cited book in science, and Stereotaxic
Atlas of Rat Brain (in Chinese) which based on Wistar rats of 290 g and SD rats
of 225 g, respectively. However, rats of different weight are frequently used,
while the stereotaxic coordinates of their brain regions show obvious differences
with the rats on which the atlases were based. NEW METHOD: The craniometric
parameters were measured as accurately as possible, then curve fitting equations
obtained from the parameters were used to deduce the relative coordinates in rats
of different weight for the first time. RESULTS: The results revealed that if the
coordinates of target brain region were defined as AP(a), ML(b), DV(c) in
"standard" rats, the corresponding coordinates AP(a'),ML(b'),DV(c') for rats
weighingm(g) were described as follows: For Wistar rats using The Rat Brain in
Stereotaxic Coordinates: a' =0.138*lnm+0.1770.138*ln290+0.177*a b'
=0.055*lnm+0.5150.055*ln290+0.515*b c' =0.054*lnm+0.7060.054*ln290+0.706*c
0.00012*m-290 and for SD rats using Stereotaxic Atlas of Rat Brain(in Chinese):
a' =0.127*lnm+0.1760.127*ln225+0.176*a b'=0.049*ln?m+0.5560.049*ln?225+0.556*b c'
=0.077*lnm+0.6040.077*ln225+0.604*c-0.00010*m-225 Unit of a, b, c, a', b', c' are
centimeter, unit of m is gram. Comparison with existing method: The Rat Brain in
Stereotaxic Coordinates is applicable for rats weighing about 290 g, while our
equations extended the use of atlas to rats weighing 90-400 g. CONCLUSIONS: In
this manner, the application of the rat brain atlases could be extended and the
results would be of great help in stereotaxic procedures.
PMID- 29960032
TI - The role of the retinal pigment epithelium and Muller cells secretome in
neovascular retinal pathologies.
AB - Secreted trophic factors are key to maintain the structural and functional
integrity of the retina, as they regulate cellular pathways responsible for
survival, function, and response to injury. Nevertheless, these same factors can
also be involved in retinal pathologies, as a consequence of the impairment of
the secretory function of cells. The cells considered as major contributors to
the retinal secretome are the retinal pigmented epithelium (RPE) and Muller
cells. Their role in the pathophysiology of the most common neovascular
pathologies in the retina - Age-related Macular Degeneration (AMD), Diabetic
Retinopathy (DR), and Retinopathy of Prematurity (ROP) - is highlighted in this
short review, together with current trophic factor-based therapies, which are
mainly focused on controlling inflammation, cell survival, and angiogenesis.
PMID- 29960031
TI - A new xanthatin analogue 1beta-hydroxyl-5alpha-chloro-8-epi-xanthatin induces
apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition
in human hepatocellular carcinoma.
AB - 1beta-hydroxyl-5alpha-chloro-8-epi-xanthatin (XTT), a sesquiterpene lactone
isolated from Xanthium sibiricum, possessed potent cytotoxicity on cancer cells
in vitro. The objective of this study was to investigate the anti-tumor effect
and underlying mechanisms of XTT on human hepatocellular carcinoma (HCC).
Firstly, XTT inhibited the cell growth and induced apoptosis in human HCC cells,
which was associated with the induction of Bax and cleaved-caspase-3, inhibition
of Bcl-2 and survivin expression. Importantly, XTT induced the generation of
reactive oxygen species (ROS) and malondialdehyde (MDA), and depletion of
glutathione (GSH) in HCC cells through covalently modification of GSH.
Furthermore, XTT caused obvious activation of extracellular regulated protein
kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) and inactivation
of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3)
in HCC cells. ROS scavenger N-acetyl cysteine abrogated the effects of XTT on
ERK/p38 MAPK activation and JAK2/STAT3 inhibition, and rescued HCC cells from XTT
induced apoptosis. Additionally, inhibitors of ERK/p38 MAPKs or activator of
JAK2/STAT3 partially abolished XTT-mediated effect. In summary, XTT inhibited
cell growth and induced apoptosis in HCC cells through ROS-mediated ERK/p38 MAPK
activation and JAK2/STAT3 inhibition by GSH depletion. These findings also show
the therapeutic potential of XTT in HCC.
PMID- 29960033
TI - Integration of the human exposome with the human genome to advance medicine.
AB - Identifying precise and predictive biomarkers of health and disease is a critical
objective of clinical biochemistry and biomedical research. New concepts and
technologies have emerged recently that could support such an objective. The
exposome corresponds to the totality of exposure over the lifetime. Research in
this field allowed the development of sensors and biological biomarkers using
omics technologies that are relevant for predicting the effect of those exposure
on human health. Precision medicine has primarily focused on adapting treatments
to the genetic profiles of tumors, when in fact, it had originally a wider scope
including the use of robust biomarkers for disease prevention. Large-scale
genetic studies have also contributed to highlight gene environment interactions,
and were extended more recently to epigenetics. In line with the systems medicine
approach, we propose to integrate the genome and exposome data in what we present
as the exposome-genome paradigm. Such an integrated view will help strengthen
approaches to identify relevant predictive markers that can support precise
prevention actions both at the population and at the individual levels.
PMID- 29960034
TI - Identification of 7alpha,24-dihydroxy-3-oxocholest-4-en-26-oic and 7alpha,25
dihydroxy-3-oxocholest-4-en-26-oic acids in human cerebrospinal fluid and plasma.
AB - Dihydroxyoxocholestenoic acids are intermediates in bile acid biosynthesis. Here,
using liquid chromatography - mass spectrometry, we confirm the identification of
7alpha,24-dihydroxy-3-oxocholest-4-en-26-oic and 7alpha,25-dihydroxy-3-oxocholest
4-en-26-oic acids in cerebrospinal fluid (CSF) based on comparisons to authentic
standards and of 7alpha,12alpha-dihydroxy-3-oxocholest-4-en-26-oic and 7alpha,x
dihydroxy-3-oxocholest-4-en-26-oic (where hydroxylation is likely on C-22 or C
23) based on exact mass measurement and multistage fragmentation. Surprisingly,
patients suffering from the inborn error of metabolism cerebrotendinous
xanthomatosis, where the enzyme CYP27A1, which normally introduces the (25 R)26
carboxylic acid group to the sterol side-chain, is defective still synthesise
7alpha,24-dihydroxy-3-oxocholest-4-en-26-oic acid and also both 25 R- and 25 S
epimers of 7alpha,12alpha-dihydroxy-3-oxocholest-4-en-26-oic acid. We speculate
that the enzymes CYP46A1 and CYP3A4 may have C-26 carboxylase activity to
generate these acids. In patients suffering from hereditary spastic paraplegia
type 5 the CSF concentrations of the 7alpha,24- and 7alpha,25-dihydroxy acids are
reduced, suggesting an involvement of CYP7B1 in their biosynthesis in brain.
PMID- 29960036
TI - Contact lenses with dual drug delivery for the treatment of bacterial
conjunctivitis.
AB - Currently, bacterial conjunctivitis is treated by frequent administration of
antibiotic eye drop solutions, which is tedious and patient noncompliant. Contact
lenses could be ideal medical devices to sustain the release of ophthalmic drugs,
but the incorporation of the latter can alter the optical and physical properties
of the lenses. In addition, many contact lens users have reported the pink eye
syndrome, making them unsuitable as ocular medical devices. In the present study,
we have designed a novel type of lenses containing semi-circular rings loaded
with moxifloxacin HCl (a broad spectrum antibiotic) and hyaluronic acid (a
comfort agent), respectively, in order to treat bacterial conjunctivitis without
altering the critical lens properties. The drug loaded rings were implanted
separately within the periphery of the contact lenses using the modified cast
moulding technology. The atomic force microscopy report showed an average
roughness of 22.27 nm for the implant lens, which was significantly lower in
comparison to the marketed Freshlook(r) (116.27 nm) contact lens. The major
amount of moxifloxacin HCl was leached (68.16-74.55%) during the monomer
extraction and wet sterilization (autoclave) steps; hence the lenses were
terminally sterilized by radiation and packaged under dry condition (dehydrated).
The in vitro release data showed release for moxifloxacin HCl and hyaluronic acid
up to 96 h. The in vivo drug release studies showed significant improvement [>MIC
for Staphylococcus aureus] in the drug residence time in comparison to the eye
drop therapy. The in vivo efficacy study in the staphylococcus aureus induced
conjunctivitis showed equivalent healing effect with the single implant contact
lens in comparison to the frequent high dose eye drop therapy. The study
demonstrated the successful application of the implantation technology to co
deliver moxifloxacin HCl and hyaluronic acid from the contact lenses for the
extended period of time to treat conjunctivitis.
PMID- 29960035
TI - Diterpenoids and lignans from the leaves of Tripterygium wilfordii.
AB - Three new diterpenoids (1-3) and three new esterifying lignans (4-6) were
isolated from the leaves of Tripterygium wilfordii. The structures of these
compounds were elucidated on the basis of spectroscopic techniques (UV, IR, NMR,
HRESIMS, and ECD method). At 10 MUmol/L, compounds 4-6 showed moderate inhibitory
effects on nitric oxide production in LPS-induced macrophages with inhibitory
rate >80%.
PMID- 29960037
TI - A modified USP induction port to characterize nasal spray plume geometry and
predict turbinate deposition under flow.
AB - There is currently no in vitro technique for assessing plume geometry of nasal
sprays under airflow conditions. However, a majority of FDA approved nasal
products recommend that patients inhale during actuation. Therefore, a
reproducible in vitro test that measures plume angles under physiologically
relevant inhalation flow rates would be useful. The purpose of this study was to
adapt the recently described Plume Induction Port Evaluator (PIPE) apparatus for
nasal sprays under flow and correlate these with nasal cast deposition patterns.
Mass Median Plume Angles (MMPAs) of four nasal spray formulations with increasing
viscosities were determined using the PIPE apparatus in the absence and presence
of airflow. MMPAs were then correlated to drug deposition within 3D printed nasal
casts using airflow. We evaluated different inhalation instructions obtained from
the package insert of nasal products. MMPAs significantly reduced (narrower
angles) when using flow for the three formulations with the lowest viscosities.
An increase in the turbinate deposition was observed in the nasal casts when just
one of the nostrils was closed during inhalation, except by the highest viscosity
formulation. The turbinate deposition numerically correlated with changes in the
plume angles observed using PIPE.
PMID- 29960038
TI - Boronate-based fluorescent carbon dot for rapid and selectively bacterial sensing
by luminescence off/on system.
AB - Boronic acid, which can bind chemo-selectively and reversibly to diols, could be
used for the early detection of bacteria through its affinity-binding reaction
with diol groups on the bacterial cell wall. Herein, we describe the use of a
diol-modified fluorescent probe (DYE) conjugated to a nanosensor consisting of
phenylboronic acid-functionalized fluorescent carbon dot (FCD) to allow quenching
via the Forster resonance energy transfer (FRET) process. Phenylboronic acid is
well-known for its preferential affinity for diol-containing molecules through
cyclic ester bond formation. Therefore, in the presence of glucose-containing
bacteria, the DYE in the cyclic ester form will be released from the FCD and
replaced by the bacterial cell forming a new cyclic boronate ester bond with the
nanoparticle, inducing recovery of the fluorescence. Quantitatively, the system's
detection performance at various bacterial concentrations (101-107 CFU/mL)
reached ~100% after 60 min, indicating that the high binding affinity of the diol
moeity on the peptidoglycan (sugar)-rich bacteria was enough to displace the DYE
from the boronic acid-functionalized FCD platform. Our facile and tunable
fluorescence switch-on system was tested for its ability to detect bacteria in
water from a contaminated river. Incredibly, the system was most successful in
detecting bacteria in the contaminated river water, thus proving it to be a less
expensive and more robust affinity biosensor for the detection of contaminating
pathogens in various chemoselective ligand-based environments.
PMID- 29960039
TI - A novel approach for determination of paraquat based on dried blood spot (DBS)
extraction and UHPLC-HRMS analysis.
AB - Paraquat is an effective herbicide chemical but a highly toxic compound for
humans and animals. The measurement of paraquat concentration in blood is
important to clinic or forensic practice. Herein, a method has been developed for
the analysis of paraquat in human blood using dried blood spot (DBS) extraction
and subsequent UHPLC-HRMS analysis. Three droplets (100 MUL each) of blood were
spotted on the Whatman(r) FTA classic card and then let dry by microwave
irradiation (1200 W) for 5 min to prepare DBS. An 8 mm diameter punch was removed
from the center of DBS and extracted with 190 MUL of mobile phase (20 mM ammonium
acetate with 0.1% formic acid and 5% acetonitrile in ultra-pure water) and 10 MUL
of internal standard (paraquat-d8, 100 ng/mL). After ultrasonic treatment for 10
min, the tube was centrifuged, and the supernatant was then filtered by 0.2 MUm
membrane and injected into the UHPLC-HRMS system. The method was validated
considering the following parameters: selectivity, LOD and LLOQ, linearity,
precision, accuracy. The method showed satisfactory linearity in the range of 1
1000 ng/mL, with high determination coefficient (0.9986). LOD was 0.5 ng/mL, and
LLOQ was 1 ng/mL. Selectivity, intra and inter day precision and accuracy were
acceptable. The validated method was then applied to authentic blood samples and
has proved to be a simple, fast and reliable procedure for the determination of
paraquat in blood.
PMID- 29960040
TI - Lipid vesicles affect the aggregation of 4-hydroxy-2-nonenal-modified alpha
synuclein oligomers.
AB - Parkinson's disease (PD) and other synucleinopathies are characterized by
accumulation of misfolded aggregates of alpha-synuclein (alpha-syn). The normal
function of alpha-syn is still under investigation, but it has been generally
linked to synaptic plasticity, neurotransmitter release and the maintenance of
the synaptic pool. alpha-Syn localizes at synaptic terminals where it can bind to
synaptic vesicles as well as to other cellular membranes. It has become clear
that these interactions have an impact on both alpha-syn functional role and its
propensity to aggregate. In this study, we investigated the aggregation process
of alpha-syn covalently modified with 4-hydroxy-2-nonenal (HNE). HNE is a product
of lipid peroxidation and has been implicated in the pathogenesis of different
neurodegenerative diseases by modifying the kinetics of soluble toxic oligomers.
Although HNE-modified alpha-syn has been reported to assemble into stable
oligomers, we found that slightly acidic conditions promoted further protein
aggregation. Lipid vesicles delayed the aggregation process in a concentration
dependent manner, an effect that was observed only when they were added at the
beginning of the aggregation process. Co-aggregation of lipid vesicles with HNE
modified alpha-syn also induced cytotoxic effects on differentiated SHSY-5Y
cells. Under conditions in which the aggregation process was delayed cell
viability was reduced. By exploring the behavior and potential cytotoxic effects
of HNE-alpha-syn under acidic conditions in relation to protein-lipid
interactions our study gives a framework to examine a possible pathway leading
from a physiological setting to the pathological outcome of PD.
PMID- 29960041
TI - TIGIT-Fc alleviates acute graft-versus-host disease by suppressing CTL activation
via promoting the generation of immunoregulatory dendritic cells.
AB - Graft-versus-host disease (GVHD) is the most common complication and major
limitation of allogeneic hematopoietic stem cell transplantation. The CD226/TIGIT
CD155 signal is critical for the cross-talk between T cells and dendritic cells
(DCs). Studies have shown that blockade of the CD226-CD155 interaction, using an
anti-CD226 antibody, can significantly ameliorate GVHD. It has also been reported
that a TIGIT-Fc fusion protein exerts immunosuppressive effects by binding to
CD155 on DCs. Here, we used a mouse allogeneic acute GVHD model to explore the
therapeutic potential and mechanism of action of TIGIT-Fc. C57/BL6 and Balb/c
mice were used as hematopoietic cell graft donors and recipients, respectively.
In the TIGIT-Fc-treated mice, GVHD symptom occurrence and mortality were delayed
compared to that in isotype control group mice. Histopathological analyses
revealed that following TIGIT-Fc treatment, liver and small intestine tissue
damage was reduced with minimal lymphocytic infiltration. The percentage of
CD8+IFN-gamma+ and CD8+ granzyme B+ cells significantly decreased in the TIGIT-Fc
group. Moreover, treatment with TIGIT-Fc, even after the onset of GVHD,
ameliorated symptoms and prolonged survival. TIGIT-Fc also inhibited CD8+ T cell
activation in vitro; this was dependent on the presence of CD155 on bone marrow
derived dendritic cells (BMDCs) and on IL-10 production. In addition, TIGIT-CD155
ligation triggered both Erk phosphorylation and STAT3 nuclear translocation.
These data indicate that TIGIT plays an important role in the development of GVHD
and is an ideal molecular target to treat acute GVHD.
PMID- 29960042
TI - Modulation of cellular membrane properties as a potential therapeutic strategy to
counter lipointoxication in obstructive pulmonary diseases.
AB - Maintaining the equilibrium between saturated and unsaturated fatty acids within
membrane phospholipids (PLs) is crucial to sustain the optimal membrane
biophysical properties, compatible with selective organelle-based processes.
Lipointoxication is a pathological condition under which saturated PLs tend to
accumulate within the cell at the expense of unsaturated species, with major
impacts on organelle function. Here, we show that human bronchial epithelial
cells extracted from lungs of patients with Obstructive Pulmonary Diseases
(OPDs), i. e. Cystic Fibrosis (CF) individuals and Smokers, display a
characteristic lipointoxication signature, with excessive amounts of saturated
PLs. Reconstitution of this signature in cellulo and in silico revealed that such
an imbalance results in altered membrane properties and in a dramatic
disorganization of the intracellular network of bronchial epithelial cells, in a
process which can account for several OPD traits. Such features include
Endoplasmic Reticulum-stress, constitutive IL8 secretion, bronchoconstriction
and, ultimately, epithelial cell death by apoptosis. We also demonstrate that a
recently-identified lipid-like molecule, which has been shown to behave as a
"membrane-reshaper", counters all the lipointoxication hallmarks tested.
Altogether, these insights highlight the modulation of membrane properties as a
potential new strategy to heal and prevent highly detrimental symptoms associated
with OPDs.
PMID- 29960043
TI - Serum proteome mapping of EGF transgenic mice reveal mechanistic biomarkers of
lung cancer precursor lesions with clinical significance for human
adenocarcinomas.
AB - Atypical adenomatous hyperplasia (AAH) of the lung is a pre-invasive lesion (PL)
with high risk of progression to lung cancer (LC). However, the pathways involved
are uncertain. We searched for novel mechanistic biomarkers of AAH in an EGF
transgenic disease model of lung cancer. Disease regulated proteins were
validated by Western immunoblotting and immunohistochemistry (IHC) of control and
morphologically altered respiratory epithelium. Translational work involved
clinical resection material. Collectively, 68 unique serum proteins were
identified by 2DE-MALDI-TOF mass spectrometry and 13 reached statistical
significance (p < 0.05). EGF, amphiregulin and the EGFR endosomal sorting protein
VPS28 were induced up to 5-fold while IHC confirmed strong induction of these
proteins. Furthermore, ApoA1, alpha-2-macroglobulin, and vitamin-D binding
protein were nearly 6- and 2-fold upregulated in AAH; however, ApoA1 was
oppositely regulated in LC to evidence disease stage dependent regulation of this
tumour suppressor. Conversely, plasminogen and transthyretin were highly
significantly repressed by 3- and 20-fold. IHC confirmed induced ApoA1, Fetuin-B
and transthyretin expression to influence calcification, inflammation and tumour
infiltrating macrophages. Moreover, serum ApoA4, ApoH and ApoM were 2-, 2- and 6
fold repressed; however tissue ApoM and sphingosine-1-phosphate receptor
expression was markedly induced to suggest a critical role of sphingosine-1
phosphate signalling in PL and malignant transformation. Finally, a comparison of
three different LC models revealed common and unique serum biomarkers
mechanistically linked to EGFR, cMyc and cRaf signalling. Their validation by IHC
on clinical resection material established relevance for distinct human lung
pathologies. In conclusion, we identified mechanistic biomarker candidates
recommended for in-depth clinical evaluation.
PMID- 29960044
TI - Interaction of PEGylated interferon-beta with antibodies to recombinant
interferon-beta.
AB - Because PEGylated molecules exhibit different physicochemical properties from
those of the parent molecules, PEGylated interferonbeta-1a (pegIFNbeta-1a) may be
able to be used with retained bioactivity in Multiple Sclerosis (MS) patients who
have previously developed neutralizing antibodies (NABs) to recombinant
interferonbeta (rIFNbeta). Hence, the objective of the present study was to test
whether pegIFNbeta-1a is less antigenic for NABs in vitro than rIFNbeta. Two in
vitro assays were used to quantitate NABs in 115 sera obtained from MS patients
included in the INSIGHT study: the cytopathic effect (CPE) assay, and the MxA
protein induction assay. NABs cross-reactivity was assessed by comparing
dilutions of serum with fixed doses of rIFNbeta-1a Avonex(r) and pegIFNbeta-1a
Plegridy(r). NABs were shown to cross-react in both assays. The y-intercept (c),
the slope of the line of agreement (b), the Pearson coefficients as well as the
Bland-Altman analysis, indicated that there is good level of agreement between
NAB titers against the two IFNbeta-1a formulations, with both the CPE (c = 0.1044
+/- 0.1305; b = 0.8438 +/- 0.06654; r2 = 0.587; bias index +/- SD = -0.01702 +/-
0.6334), and the MxA protein induction (c = 0.08246 +/- 0.1229; b = 0.8878 +/-
0.06613; r2 = 0.615; bias index +/- SD = -0.09965 +/- 0.6467) assays. Until
further in vivo evidence is established, clinicians should consider the current
in vitro data demonstrating NAB cross-reactivity between pegIFNbeta-1a and
rIFNbeta when discussing new treatment options with MS patients.
PMID- 29960045
TI - Synaptic Mitochondria are More Susceptible to Traumatic Brain Injury-induced
Oxidative Damage and Respiratory Dysfunction than Non-synaptic Mitochondria.
AB - Traumatic brain injury (TBI) results in mitochondrial dysfunction and induction
of lipid peroxidation (LP). Lipid peroxidation-derived neurotoxic aldehydes such
as 4-HNE and acrolein bind to mitochondrial proteins, inducing additional
oxidative damage and further exacerbating mitochondrial dysfunction and LP.
Mitochondria are heterogeneous, consisting of both synaptic and non-synaptic
populations. Synaptic mitochondria are reported to be more vulnerable to injury;
however, this is the first study to characterize the temporal profile of synaptic
and non-synaptic mitochondria following TBI, including investigation of
respiratory dysfunction and oxidative damage to mitochondrial proteins between 3
and 120 h following injury. These results indicate that synaptic mitochondria are
indeed the more vulnerable population, showing both more rapid and severe
impairments than non-synaptic mitochondria. By 24 h, synaptic respiration is
significantly impaired compared to synaptic sham, whereas non-synaptic
respiration does not decline significantly until 48 h. Decreases in respiration
are associated with increases in oxidative damage to synaptic and non-synaptic
mitochondrial proteins at 48 h and 72 h, respectively. These results indicate
that the therapeutic window for mitochondria-targeted pharmacological
neuroprotectants to prevent respiratory dysfunction is shorter for the more
vulnerable synaptic mitochondria than for the non-synaptic population.
PMID- 29960046
TI - Expanding the phenotypic spectrum associated with OPHN1 variants.
AB - Genomic sequencing has allowed for the characterization of new gene-to-disease
relationships, as well as the identification of variants in established disease
genes in patients who do not fit the classically-described phenotype. This is
especially true in rare syndromes where the clinical spectrum is not fully known.
After a lengthy and costly diagnostic odyssey, patients with atypical
presentations may be left with many questions even after a genetic diagnosis is
identified. We present a 22-year old male with hypotonia, developmental delay,
seizure disorder, and dysmorphic facial features who enrolled in our rare disease
research center at 18 years of age, where exome sequencing revealed a novel,
likely pathogenic variant in the OPHN1 gene. Through efforts by the study team
and collaborations with the larger genetics community, contacts with other
families with OPHN1 variants were eventually made, and outreach by these families
expanded the patient network. This partnership between families and researchers
facilitated the gathering of phenotypic information, allowing for comparison of
clinical presentations among three new patients and those previously reported in
the literature. These comparisons found previously unreported commonalities
between the newly identified patients, such as the presence of otitis media and
the lack of genitourinary abnormalities (i.e. hypoplastic scrotum, microphallus,
cryptorchidism), which had been noted to be classic features of patients with
OPHN1 variants. As genomic sequencing becomes more common, connecting patients
with novel variants in the same gene will facilitate phenotypic analysis and
continue to refine the clinical spectrum associated with that gene.
PMID- 29960047
TI - An 18 bps in-frame deletion mutation in RUNX2 gene is a population polymorphism
rather than a pathogenic variant.
AB - We recruited a family with an affected child exhibiting features of cleidocranial
dysplasia with some phenotypic variations from reported cases. Whole exome
sequencing data analysis identified an 18-bps heterozygous in-frame deletion
variant (c.243-260delGGCGGCTGCGGCGGCGGC) in the RUNX2 gene. Sanger sequencing
validated the presence of deletion in affected individual. Initially, we
considered this variant as a causal mutation for the patient's phenotype based on
previous report(s). However, further analysis of variant revealed that it is
present in high frequency in variety of genome variation databases. Moreover,
segregation analysis discovered the presence of variant in mother as well.
Furthermore, screening of population matched control individuals revealed that
the variant is present in apparently healthy individuals as well. Three
dimensional structures of the wild-type and mutant RUNX2 protein
(p.Ala82_Ala87del) were analysed and it was found that both wild type and mutant
protein show similar secondary structure pattern. Presence of RUNX2 deletion
variant (c.243-260delGGCGGCTGCGGCGGCGGC) in control individuals, its high
population frequency, benign effect on the overall protein structure lead to the
argument that this variant is a population polymorphism and not a pathogenic
mutation.
PMID- 29960048
TI - Targeting cancer stem cells with dietary phytochemical - Repositioned drug
combinations.
AB - The tumor microenvironment is complex with the cancer stem cell (CSC) as a member
within its community. This population possesses the capacity to self-renew and to
cause cellular heterogeneity of the tumor. CSCs are resistant to conventional
anti-proliferative drugs. In order to be curative, it is imperative that CSCs
must be eliminated by cancer therapy. A variety of dietary phytochemicals and
repositioned drugs can act synergistically with conventional anti-cancer agents.
In this review, we advocate the development of a novel approach, namely
combination therapy by incorporating both phytochemicals and repositioned drugs
to target CSCs. We cover select dietary phytochemicals (curcumin, resveratrol,
EGCG, genistein) and repurposed drugs (metformin, niclosamide, thioridazine,
chloroquine). Five of the eight (curcumin, resveratrol, EGCG, genistein,
metformin) are listed in "The Halifax Project", that explores "the concept of a
low-toxicity 'broad-spectrum' therapeutic approach that could simultaneously
target many key pathways and mechanisms" [1]. For these compounds, we discuss
their mechanisms of action, in which models their anti-CSC activities were
identified, as well as advantages, challenges and potentials of combination
therapy.
PMID- 29960049
TI - Deleting MyD88 signaling in myeloid cells promotes development of adenocarcinomas
of the colon.
AB - Intestinal myeloid cells are not only essential for keeping local homeostasis,
but also play an important role in regulating the occurrence of colitis and
colitis-associated cancer (CAC). In these diseases, the manner in which the
myeloid cells work and which molecular pathways influence them are still not
fully understood. In our study, we discovered that MyD88 signaling in colonic
myeloid cells participates in the development of CAC. Myeloid MyD88-deficient
mice showed greater susceptibility to azoxymethane (AOM)/dextran sodium sulfate
(DSS)-induced CAC, as evidenced by the increase in the number and sizes of
tumors. Myeloid MyD88 deletion markedly increased production of pro-inflammatory
and pro-tumor cytokines; recruitment of more IL-1beta producing-neutrophils in
colon from bone marrow; increased in epithelial cell apoptosis and decreased in
epithelial cell proliferation; enhancement of colon mucosal expression of COX-2,
p-STAT3, beta-catenin, and cyclinD1; induction of further DNA damage and beta
catenin mutation. To sum up, these results suggest that myeloid MyD88 signaling
protects the intestine from tumorigenesis during the development of CAC.
PMID- 29960050
TI - N-alpha-acetyltransferase 10 protein promotes metastasis by stabilizing matrix
metalloproteinase-2 protein in human osteosarcomas.
AB - N-alpha-Acetyltransferase 10 protein (Naa10p) mediates N-terminal acetylation of
nascent proteins. Oncogenic or tumor suppressive roles of Naa10p were reported in
cancers. Here, we report an oncogenic role of Naa10p in promoting metastasis of
osteosarcomas. Higher NAA10 transcripts were observed in metastatic osteosarcoma
tissues compared to non-metastatic tissues and were also correlated with a worse
prognosis of patients. Knockdown and overexpression of Naa10p in osteosarcoma
cells respectively led to decreased and increased cell migratory/invasive
abilities. Re-expression of Naa10p, but not an enzymatically inactive mutant,
relieved suppression of the invasive ability in vitro and metastasis in vivo
imposed by Naa10p-knockdown. According to protease array screening, we identified
that matrix metalloproteinase (MMP)-2 was responsible for the Naa10p-induced
invasive phenotype. Naa10p was directly associated with MMP-2 protein through its
acetyltransferase domain and maintained MMP-2 protein stability via NatA complex
activity. MMP-2 expression levels were also significantly correlated with Naa10p
levels in osteosarcoma tissues. These results reveal a novel function of Naa10p
in the regulation of cell invasiveness by preventing MMP-2 protein degradation
that is crucial during osteosarcoma metastasis.
PMID- 29960051
TI - Cancer-type organic anion transporting polypeptide 1B3 is a target for cancer
suicide gene therapy using RNA trans-splicing technology.
AB - Cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3) has been
identified as a cancer-specific transcript in various solid cancers, including
colorectal cancer. Given its excellent cancer-specific expression profile, we
hypothesized that Ct-OATP1B3 could represent a promising target for cancer
specific expression of the suicide gene, herpes simplex virus 1 thymidine kinase
(HSV-tk), via a spliceosome-mediated RNA trans-splicing (SMaRT) approach. SMaRT
technology is used to recombine two RNA molecules to generate a chimeric
transcript. In this study, we engineered an RNA trans-splicing molecule carrying
a translation-defective HSV-tk sequence (RTM44), which was capable of inducing
its own trans-splicing to the desired Ct-OATP1B3 pre-mRNA target. RTM44
expression in LS180 cells resulted in generation of Ct-OATP1B3/HSV-tk fusion
mRNA. A functional translation start site contributed by the target pre-mRNA
restored HSV-tk protein expression, rendering LS180 cells sensitive to
ganciclovir treatment in vitro and in xenografted mice. The observed effects are
ascribed to accurate and efficient trans-splicing, as they were absent in cells
carrying a splicing-deficient mutant of RTM44. Collectively, our data highlights
Ct-OATP1B3 as an ideal target for the HSV-tk SMaRT suicide system, which opens up
new translational avenues for Ct-OATP1B3-targeted cancer therapy.
PMID- 29960053
TI - Decreased parvalbumin and somatostatin neurons in medial prefrontal cortex in
BRINP1-KO mice.
AB - BRINPs (BMP/RA-inducible Neural Specific Protein-1, 2, 3) are family genes
expressed mainly in both the central and peripheral nervous system. BRINP1 is
abundantly expressed in many of adult brain regions including cerebral cortex and
hippocampus, with expression regulated in an activity-dependent manner in the
dentate gyrus. Mice with disrupted BRINP1 gene exhibit abnormal behaviors such as
increased locomotive activity and poor social activity which are analogous to
symptoms of human psychiatric disorders such as schizophrenia (SCZ), autism
spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). In
the present study, to clarify the physiological roles of BRINP1 in psychiatric
disorders, we examined the numbers of parvalbumin (PV)-expressing neurons and
somatostatin (SST)-expressing neurons in the medial prefrontal cortex (mPFC) in
BRINP1-KO mice. Immunohistochemical analysis revealed the numbers of PV
expressing neurons and SST-expressing neurons in mPFC of BRINP1-KO mice were,
respectively, 50% and 20% fewer than corresponding neurons in mPFC of wild-type
mice. These data suggest that the abnormal behaviors related to human psychiatric
disorders in BRINP1-KO mice could be derived from the hyperexcitability of
pyramidal neurons as a consequence of decreased inhibitory innervation and
conceivable dysregulation of the Excitatory/Inhibitory balance in mPFC.
PMID- 29960052
TI - Effects of nerve growth factor neutralization on TRP channel expression in laser
captured bladder afferent neurons in mice with spinal cord injury.
AB - Nerve growth factor (NGF) is reportedly involved in the changes in C-fiber
bladder afferent pathways that induce detrusor overactivity (DO) following spinal
cord injury (SCI). This study examined the roles of NGF in TRP channel expression
in bladder afferent neurons in mice with SCI using laser-capture microdissection
(LCM) methods. Spinal intact (SI) and SCI mice were divided into 3 groups: (1) SI
with vehicle treatment; (2) SCI with vehicle treatment; and (3) SCI with anti-NGF
antibody. Two weeks after SCI, an osmotic pump was placed subcutaneously into the
back of the mice and vehicle or anti-NGF antibody was administered at a rate of
10 MUg/kg per hour for two weeks. Four weeks after SCI, the L6 dorsal root
ganglia (DRG) were removed. Expression of the TRPV1, TRPC1, TRPC3, and TRPC6
genes was analyzed using real-time polymerase chain reaction (PCR) following LCM
of the bladder afferent neurons, which were labeled by Fast Blue injected into
the bladder wall 1 week prior to tissue removal. The mRNA expression of TRPV1 was
found to be higher in vehicle-treated SCI mice than in SI mice. The expression
level of TRPC3 and TRPC6 in vehicle-treated SCI mice was lower than in SI mice.
However, in SCI mice treated with anti-NGF antibody, the mRNA expression of TRPV1
was lower, and the mRNA levels of TRPC3 and TRPC6 were higher than in vehicle-SCI
mice. These results suggest that the NGF-dependent changes in specific TRP
channel genes, such as TRPV1, TRPC3, and TRPC6, could be involved in SCI-induced
afferent hyperexcitability and DO.
PMID- 29960054
TI - Non-invasive brain stimulation to enhance cognitive rehabilitation after stroke.
AB - Stroke is a main cause for long-term disability. Stroke symptoms cover various
domains, e.g., motor, sensory, language, or other cognitive functions. In
clinical practice and rehabilitation research, especially motor impairment
attracts much attention. However, also cognitive impairments are common after
stroke, effecting approximately two-thirds of stroke patients in the acute phase.
Although 30% of stroke patients spontaneously recover from their cognitive
impairments, large amounts of patients remain cognitively impaired. These
patients have more problems reintegrating in personal and professional life. To
date, cognitive rehabilitation strategies are not yet satisfactory. One promising
strategy is combining non-invasive brain stimulation (NIBS) with cognitive
training. In the current review, we will discuss the relevance of cognitive
impairment after stroke and innovative interventional strategies to improve
cognition, such as NIBS. Furthermore, we will address the potential of using
cognitive training to enhance recovery in other behavioural domains, such as the
motor domain.
PMID- 29960056
TI - Short-afferent inhibition and cognitive impairment in Parkinson's disease: A
quantitative review and challenges.
AB - Traditionally, Parkinson's disease (PD) has been considered a single
neurotransmitter (dopaminergic) disease. However, research over the past 20 years
has shed light on the involvement of multiple neurotransmission systems, in
particular, the cholinergic system. Research has mainly focused on the role of
this system in the pathophysiology of PD and its implications in the development
of motor and non-motor disorders. Short-latency sensory afferent inhibition
(SAI), investigates sensori-motor integration, and has emerged as a putative
neurophysiological marker of cholinergic function in the human brain. In this
quantitative review, a moderate-to-severe reduction in SAI was observed in PD
patients. Furthermore, through moderator analysis, the impairment of SAI was
shown to be associated with disease duration and therapeutic state. Patients
under dopaminergic agents ("on" state) displayed worse SAI than those after
dopaminergic agent withdrawal ("off"). We further assess the potential value of
SAI as a marker of cognitive impairment in PD, and its association with four
specific cognitive domains. This analysis revealed that patients with cognitive
impairment displayed significantly lower levels of SAI than those without
cognitive impairment. To conclude, a set of challenges to be addressed before SAI
can be validated as a useful clinical tool in PD are presented.
PMID- 29960055
TI - cGMP mediates short- and long-term modulation of excitability in a decision
making neuron in Aplysia.
AB - In elementary neural circuits, changes in excitability can have a strong impact
in the expression of a given behavior. One example is provided by B51, a neuron
with decision-making properties in the feeding neural circuit of the mollusk
Aplysia. The excitability of B51 is bidirectionally modulated by external and
internal stimuli in a manner that is consistent with the corresponding induced
changes in feeding behavior. For example, in operant reward learning, which up
regulates feeding, B51 excitability is increased via a cAMP-dependent mechanism.
Conversely, following training protocols with aversive stimuli, which down
regulate feeding, B51 excitability is decreased. In this study, we tested the
hypothesis that B51 decreased excitability may be mediated by another cyclic
nucleotide, cGMP. Our results revealed that iontophoretic injection of cGMP was
capable of inducing both short-term (45 min) and long-term (24 h) reduction of
B51 excitability. We next investigated which biochemical trigger could increase
cGMP cytosolic levels. The neurotransmitter nitric oxide was found to decrease
B51 excitability through the activation of the soluble guanylyl cyclase. These
findings indicate that a cGMP-dependent pathway modulates B51 excitability in a
manner opposite of cAMP, indicating that distinct cyclic-nucleotide pathways
bidirectionally regulate the excitability of a decision-making neuron.
PMID- 29960057
TI - Osteoradionecrosis of the Skull Base in Nasopharyngeal Carcinoma: Incidence and
Risk Factors.
AB - PURPOSE: Nasopharyngeal carcinoma (NPC) is a type of malignancy with a high
prevalence in southern China and Southeast Asia. The primary treatment modality
is radiation therapy (RT). Osteoradionecrosis (ORN) of the skull base remains one
of the most serious complications after RT, affecting survival time and quality
of life. Thus far, skull base ORN has been seldom reported and can be difficult
to distinguish and easy to misdiagnose. In this retrospective study, we report
the incidence of skull base ORN and analyze its associated factors in an attempt
to decrease the occurrence of ORN. METHODS AND MATERIALS: From January 2001 to
December 2012, a total of 1348 patients who received diagnoses of NPC received 1
course of RT. Complete medical records were reviewed, and the patients were
examined by magnetic resonance imaging and nasopharyngeal endoscopy during follow
up after primary treatment. Patients with other tumors of the head and neck, a
history of RT, failure to complete RT, and those lost to follow-up were excluded.
Treatment was delivered with external beam RT using standard linear accelerators.
RESULTS: A total of 1348 patients with NPC were enrolled in this study after 1
course of RT; among these patients, 14 received diagnoses of skull base ORN. The
incidence of skull base ORN was 1.04%. The average latency interval from the
completion of RT to the diagnosis of skull base ORN was 45.57 months. Skull base
ORN after 1 course of RT was associated with the T stage; total radiation dose to
the nasopharynx, including the skull base in the radiation field; and anemia.
CONCLUSIONS: The occurrence of skull base ORN was associated with primary tumors
with advanced T stages, high doses of nasopharynx RT, and radiation fields that
included the skull base. These factors may be used as predictors for the
incidence of skull base ORN.
PMID- 29960058
TI - The Relationship Between Preresidency Peer-Reviewed Publications and Subsequent
Citation-Based Scholarly Activity of United States Radiation Oncology Residents.
AB - PURPOSE: Preresidency peer-reviewed publications (PRP) have been associated with
resident choice of academic versus private practice careers in both neurosurgery
and radiation oncology. The relationship between PRP and subsequent citation
based scholarly activity of radiation oncology residents has not been previously
examined. METHODS AND MATERIALS: A list of 2016 radiation oncology resident
graduates (163 residents from 76 Accreditation Council for Graduate Medical
Education-certified programs) and their PRP were compiled. The Scopus
bibliometric citation database was then searched to collect Hirsch index (h
index) data for each resident, as well as manuscripts limited to first-author
only and first- or second-author only for each resident. Analyses were stratified
based on the absence or presence of (at least 1) PRP for each resident. RESULTS:
The mean h-index score for all resident graduates was 4.15. Residents with at
least 1 PRP had significantly higher h-index scores (5.93 vs 2.12; P < .01) than
those with no PRP. PRP was also associated with significantly higher first-author
only (2.84 vs 1.17; P < .01) and second-author only (3.90 vs 1.47; P < .01)
scores. CONCLUSIONS: Radiation oncology residents with at least 1 PRP are
significantly more likely than those with no PRP to have higher h-index scores,
as well as higher scores when stratified by first and/or second authorship. The
average radiation oncology resident graduate with at least 1 PRP has published
approximately 6 manuscripts cited at least 6 times, been first or second author
on nearly 4 manuscripts cited at least 4 times, and been first author on nearly 3
manuscripts cited at least 3 times. More than 30% of graduates without PRP did
not publish any cited manuscripts. These results allow for potential predictive
evaluation of resident productivity during the radiation oncology residency
applicant process and have potential utility in predicting career choices
postresidency.
PMID- 29960059
TI - Impact of Immunohistochemistry-Based Subtypes in Muscle-Invasive Bladder Cancer
on Response to Chemoradiation Therapy.
AB - PURPOSE: A bladder-sparing strategy is a useful option for patients with muscle
invasive bladder cancer (MIBC), in which the response to chemoradiation therapy
(CRT) is primarily important in achieving favorable oncologic outcomes. Our
objective is to evaluate the impact of immunohistochemistry (IHC)-based subtyping
in MIBC on prediction of CRT response. METHODS AND MATERIALS: Treatment protocol
consisted of induction CRT followed by partial or radical cystectomy as
consolidative surgery; 118 eligible patients with nonmetastatic MIBC were
retrospectively analyzed. Of these patients, 92 eventually underwent partial or
radical cystectomy after CRT. We applied the IHC-based subtyping model developed
by Lund University, which classifies patients into urobasal (Uro), genomically
unstable (GU), and squamous cell cancer-like (SCCL) subtypes. GU and SCCL cancers
are supposed to be highly aggressive and to have worse prognoses than Uro.
Correlations of subtypes with CRT response were analyzed clinically in all
patients and pathologically in 92 cystectomized patients. The impact of each
subtype on cancer-specific mortality (CSM) was also analyzed. RESULTS: Of all
patients, 26 (22%), 61 (52%), and 31 (26%) were classified into Uro, GU, and SCCL
subtypes, respectively. Clinical complete response (CR) was achieved in 42% of
patients overall after CRT, with a significantly higher proportion in GU patients
(52%) and SCCL patients (45%) than in Uro patients (15%; P < .001 and P = .01,
respectively). On multivariate analysis, the GU/SCCL subtype was a significant
predictor of clinical CR, as was absence of hydronephrosis or concomitant
carcinoma in situ. Analyses for pathologic CR in the cystectomized patients
revealed analogous findings. Five-year CSM of Uro, GU, and SCCL patients was 16%,
23%, and 28% overall, respectively, and 19%, 22%, and 23% in cystectomized
patients, respectively, with no significant difference among the subtypes. CR
status after CRT was significantly and independently correlated with low CSM in
both clinical and pathologic evaluations. CONCLUSIONS: GU and SCCL cancers showed
significantly more favorable CRT response than did Uro cancers. IHC-based
subtyping may improve clinical decisions about the indication of CRT for MIBC
patients.
PMID- 29960060
TI - Significance of Negative Posttreatment 18-FDG PET/CT Imaging in Patients With
p16/HPV-Positive Oropharyngeal Cancer.
AB - PURPOSE: Patients with p16/human papilloma virus (HPV)-associated oropharyngeal
squamous cell carcinoma have a favorable outcome after treatment. In this group
of patients who could have a long life expectancy, the optimal surveillance
strategy and modality is not well established. We aim to determine the ability of
a negative postradiation positron emission tomography (PET)/computed tomography
scan to predict the risk of subsequent relapse in these patients. MATERIALS AND
METHODS: A retrospective analysis of patients with p16/HPV-associated
oropharyngeal squamous cell carcinoma who completed definitive (chemo)radiation
therapy and had a posttreatment PET/computed tomography scan from 2006 to 2013
was performed. Patient, tumor, and treatment characteristics and clinical
outcomes were recorded. Tumors were considered HPV/p16 positive if either HPV (by
in situ hybridization) or p16 (by immunohistochemistry) was positive. Disease
free survival and overall survival rates were estimated using the Kaplan-Meier
method. RESULTS: In our study, 327 patients were evaluated. The median age was 57
years. The most common primary sites were base of tongue (50%) and tonsil (48%).
Of the patients evaluated, 291 (89%) had a negative posttreatment PET scan. For
these 291 patients who had a complete metabolic response after treatment, the 5
year disease-free survival and overall survival rates were 91% and 89%,
respectively. The median time to development of recurrence was 16 months. Of the
291 patients, 24 patients (8%) had disease recurrence; 13 recurrences were
locoregional, and 13 were distant. Eleven (4%) patients with recurrence had
further surgery or radiation, and 8 patients (3%) were without disease as of the
last follow-up. CONCLUSIONS: Patients who achieve a complete metabolic response
on posttreatment PET imaging have an excellent prognosis, and the risk of
developing a recurrence in the future is very low. Therefore, a more cost
effective surveillance program should be considered for this subgroup of
patients.
PMID- 29960061
TI - Dietary administration of eryngii mushroom (Pleurotus eryngii) powder on haemato
immunological responses, bactericidal activity of skin mucus and growth
performance of koi carp fingerlings (Cyprinus carpio koi).
AB - The aim of present study was to evaluate the effects of edible eryngii mushroom
powder, Pleurotus eryngii (PE), for 63 days on haematological parameters, the
serum immune responses, skin mucus, bactericidal activity, stress resistance,
growth performance and digestive enzyme activities of Koi carp fingerlings
(Cyprinus carpio koi). Fish were divided into five groups and each group was fed
with dietary PE with five graded levels (0, 0.5, 1, 1.5 and 2%). The results
showed a significant dose-dependent increase of Ht, Hb, MCV and MCH levels in
fish fed dietary PE (P < 0.05). The highest levels of WBCs, lymphocytes and
monocytes were measured in fish fed 1.5% and 2% of dietary PE (P < 0.05). The
activities of total IG, lysozyme, Alternative haemolytic complement activity in
serum of fish fed with 2% of dietary PE for 63 days as well as 5-min air exposure
challenge test were significantly higher than other groups (P < 0.05). The most
bactericidal activity was observed in skin mucus of fish fed with 1.5% of dietary
PE against Streptococcus iniae (P < 0.05). The highest ratio of the lactobacillus
count to the total viable count was observed in fish fed 2% of dietary PE. The
alpha-amylase activity of fish fed with dietary PE (1, 1.5 and 2%) were
significantly higher than control group (P < 0.05). Feeding fish 2% of dietary PE
increased the trypsin and lipase activity compared to others groups (P < 0.05).
The growth performance of fish fed 1.5% of dietary PE improved compared to
control group (P < 0.05). The results revealed that feeding koi fish with dietary
supplementation of PE (1.5 and 2%) improved the selected humoral innate immune
responses, bactericidal activity of skin mucus and growth performance of koi
fish.
PMID- 29960062
TI - Ctenopharyngodon idella TBK1 activates innate immune response via IRF7.
AB - In mammals, IFN regulatory factor (IRF) 7 is a central regulator of IFN-alpha
expression in response to variable pathogenic infections. There are several
pathogenic sensors involved in monitoring pathogen intrusion in mammals. These
sensors trigger IRF7-mediated responses through different pathways. TANK-binding
kinase 1 (TBK1) is a critical mediator of IRF7 activation upon pathogen
infection. In fish, there are many reports on TBK1, IRF3 and IRF7, especially on
TBK1-IRF3 signaling pathway. However, it is not very clear how TBK1-IRF7 works in
innate immune signaling pathway. In this study, we explored how TBK1 up-regulates
IFN, ISG expression, and how TBK1 initiates innate immune response through IRF7
in fish under lipopolysaccharides (LPS) stimulation. After stimulation with LPS,
grass carp IRF3 and IRF7 transcriptions were up-regulated, indicating they
participate in TLR-mediated antiviral signaling pathway. It is interesting that
the response time of grass carp IRF3 to LPS was earlier than that of IRF7. In
addition, IRF7 rather than IRF3 acted as a stronger positive regulator of IFN and
ISG transcription in Ctenopharyngodon idella kidney cells (CIKs). It is suggested
the potential function differentiation between IRF3 and IRF7 upon LPS infection
in fish. Dual luciferase assays also showed that overexpression of grass carp
IRF7 and TBK1 up-regulated the transcription level of IFN and PKR. However,
knockdown of IRF7 inhibits ISG expression, suggesting that grass carp TBK1
regulates the transcription via IRF7. Co-immunoprecipitation and GST pull-down
assays proved the binding of grass carp IRF7 to TBK1. Furthermore, grass carp
TBK1 can promote the nuclear translocation of IRF7. The results indicated that
grass carp TBK1 can bind directly to and activate IRF7.
PMID- 29960063
TI - A "Lamellar structure" contributes to autophagosome biogenesis and mitophagy in
zebrafish hepatocytes.
AB - Despite many studies being conducted over the past few decades, the origin of
autophagosomal membranes remains unclear. The present study aimed to uncover the
formation process of autophagosomal membranes in hepatocytes of zebrafish (Danio
rerio), a model organism in medical science. Immunohistochemistry of zebrafish
hepatocytes indicated that light chain 3-like protein 2 (LC3-II) is highly active
in some hepatocytes, but poorly expressed in others. Under transmission electron
microscopy, the amount of autophagosomes (APs) varied in different hepatocytes.
When the endoplasmic reticulum (ER) is dispersed in the cytoplasm, few isolation
membranes (IMs) and APs were observed. Subsequently, when the ER assembles into a
particular "lamellar structure" (LS), IMs arise from it and extend to enwrap the
mitochondria. With further aggregation of the ER, the LS developed into an over
twenty-layered structure, and mitophagy was more obvious in the hepatocytes and
cavities appeared in mitochondria. Finally, most ERs were assembled into several
LSs. At this point, mitophagy was most active in the hepatocytes. Thereafter,
glycogen and lipid droplet increased gradually, while the LS degenerated and ER
scatter increased. Then, the glycogen and lipid droplets dominated the
hepatocellular cytoplasm. After suppressing the formation of autophagosomes using
3-Methyladenine (3-MA), the LS could no longer be visualized in the
hepatocellular cytoplasm, and mitophagy decreased drastically. Taken together,
the results suggested that this LS in the hepatocytes of zebrafish, might be
another manifestation of a pre-autophagosomal structure in zebrafish liver,
analogous to the omegasome in yeast or the ER-IM complex in mammalian cell lines.
Furthermore, selective mitophagy and consequent cyclic utilization of its
products were probably relevant to dynamic cycle of the hepatocellular cytoplasm.
PMID- 29960064
TI - Characterization of a cold-active transglutaminase from a crayfish, Pacifastacus
leniusculus.
AB - Transglutaminase (TGase) from signal crayfish (Pacifastacus leniusculus) and its
activity at low temperatures was studied. TGase is an abundant protein in the
hematopoietic (HPT) cells and this tissue was used for TGase enzyme preparation.
The optimal temperature and pH for the activity of crayfish TGase were
determined. We found that TGase activity at 4 degrees C showed nearly the same
activity as at a temperature of 22 degrees C. TGase activity from crayfish was
compared with guinea pig liver TGase activity at 4 degrees C and the crayfish
TGase displayed a higher activity while guinea pig liver TGase had a very low
activity at this low temperature. By comparing kinetic parameters to guinea pig
liver TGase, the results showed that a high activity of crayfish TGase was due to
a decreasing Km value for pentylamine as a substrate, while it did not affect the
kcat value (at 22 degrees C). The amino acid sequences of a krill and a crayfish
TGase, which both are cold adapted, do not give any clue to why these two enzymes
are cold-adapted. These results demonstrate that crayfish TGase is adapted to
have significant activity at low temperatures and since crayfish are living in
quite cold waters this is an interesting adaptation of this enzyme.
PMID- 29960065
TI - l-glutamine in vitro supplementation enhances Nile tilapia Oreochromis niloticus
(Linnaeus, 1758) leukocyte function.
AB - Under appropriate conditions, glutamine (Gln) is an essential nutrient for
immunological responses, acting as a metabolic substrate for proliferation of
enterocytes and lymphocytes, and having positive effects on the function of
stimulated immune cells. Thus, specific components of both innate and adaptive
immune systems of Nile tilapia were evaluated after supplementing Gln to cell
culture media. Primary cell cultures of kidney leukocytes were used for
respiratory burst and phagocytic activity assessment. The ability of macrophages
to kill Streptococcus iniae also was evaluated. Additionally, a proliferation
assay was conducted with peripheral blood lymphocytes (PBL) exposed to non
specific mitogens. Results showed that macrophage phagocytosis, anion superoxide
production, and bactericidal capacity were significantly (P < 0.05) enhanced by
Gln supplementation to the culture media. The proliferation of lymphocytes upon
mitogenic exposure also was significantly (P < 0.05) enhanced by Gln
supplementation to the media. Our results suggest that in vitro, different levels
of Gln were necessary for optimal immunological responses of leukocytes and
lymphocytes. As such, Gln supplementation was able to enhance and modulate both
innate and adaptive responses of Nile tilapia leukocytes, highlighting its
potential application as an immunonutrient.
PMID- 29960066
TI - A Lysin motif (LysM)-containing protein from Hong Kong oyster, Crassostrea
hongkongensis functions as a pattern recognition protein and an antibacterial
agent.
AB - Lysin motif (LysM)-containing proteins are a family of carbohydrate-binding
modules and are generally regarded as chitin- and peptidoglycan-binding proteins.
In the present study, a novel LysM-containing protein, designated as ChLysM, was
cloned and identified in a marine mollusk, Crassostrea hongkongensis. The full
length cDNA of ChLysM consists of 1129 bp, with an open reading frame of 861 bp
encoding a 286 amino acid polypeptide. The deduced protein had a calculated
molecular mass of 32.66 kDa and a pI of 8.16. SMART analysis indicated that
ChLysM has one Lysin motif and a transmembrane region in the C-terminal residues.
Tissue distribution analysis of ChLysM revealed high expression in gills and
hemocytes. The upregulated transcripts of ChLysM in response to bacterial
challenge suggest that ChLysM is involved in innate immunity against pathogen
infection. The recombinant protein of ChLysM was found to bind to various kinds
of peptidoglycans from Staphylococcus aureus, Bacillus subtilis and Saccharomyces
cerevisiae, as well as binding strongly to both Gram-positive and Gram-negative
bacteria. Moreover, ChLysM displayed broad-spectrum antibacterial activity
against both Gram-positive bacteria (S. aureus and S. haemolyticus) and Gram
negative bacteria (Escherichia coli and Vibrio alginolyticus). Collectively,
these results indicate that ChLysM is a pattern recognition molecule with
bacterial growth-inhibiting activity in immune defense of C. hongkongensis.
PMID- 29960067
TI - LncRNA TUG1 affects cell viability by regulating glycolysis in osteosarcoma
cells.
AB - Osteosarcoma is an aggressive malignant neoplasm in teenagers and young adults.
Long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is considered as
an oncogene in osteosarcoma. However, the mechanism of TUG1 in regulating
osteosarcoma has not been fully understood. We aimed to investigate whether the
metabolic alteration is involved in the effect of TUG1 on osteosarcoma cells.
Herein, we found that TUG1 was overexpressed in osteosarcoma cells compared with
the normal osteoblastic cell line. Knockdown of TUG1 inhibited glucose
consumption, lactate production and cell viability of osteosarcoma cells.
Overexpression of TUG1 induced cell viability, whereas the induction was
attenuated by 2-DG. The aberrant expression of TUG1 markedly affected the
expression of hexokinase-2 (HK2). Knockdown of HK2 weakened the effect of TUG1
overexpression on glycolysis in osteosarcoma cells. We concluded that glycolysis
was involved in the effect of TUG1 on cell viability of osteosarcoma cells. HK2
might be an important molecule by which TUG1 affected the glycolysis.
PMID- 29960068
TI - Emerging role of nutrition and the non-coding landscape in type 2 diabetes
mellitus: A review of literature.
AB - With the advent of recent advances in molecular techniques and whole genome
sequencing, we have come to know that the non-coding landscape (including non
coding RNAs, tRNAs and even telomeres) plays a major role in the regulation of
cellular processes. Furthermore, the deregulation of this landscape has been
found to contribute to and even bring about the pathogenesis of a large number of
diseases. One of such diseases is diabetes mellitus (type 2 specifically) whose
incidence rate and global burden is constantly increasing. Nutrition has been
proven to be a key player in the development, onset and control of type 2
diabetes mellitus. Additionally, non-coding DNA based molecular markers are
emerging as biomarkers of T2D, susceptibility, and perhaps dietary supplements
can modulate non-coding DNA based markers expression and function in T2D
management. In this review, we provide a brief overview of the developmental
origins and genetics of type 2 diabetes mellitus, how each component of the non
coding landscape contributes to the development and progression of the disease
and finally we discuss how dietary interventions modulate the non-coding
landscape in T2D.
PMID- 29960069
TI - Alternative splicing of (ppp1r12a/mypt1) in zebrafish produces a novel myosin
phosphatase targeting subunit.
AB - Myosin phosphatase is an evolutionarily conserved regulator of actomyosin
contractility, comprised of a regulatory subunit (Mypt1), and a catalytic subunit
(PP1). Zebrafish has become an ideal model organism for the study of the genetic
and cell physiological role of the myosin phosphatase in morphogenesis and
embryonic development. We identified and characterized a novel splice variant of
Mypt1 (ppp1r12a-tv202) from zebrafish, which is widely expressed during early
embryonic development. Importantly, mutant alleles and antisense morpholinos that
have been used to demonstrate the important role of Mypt1 in early development,
not only disrupt the longer splice variants, but also tv202. The protein product
of ppp1r12a-tv202 (Mypt1-202) contains the PP1-binding N-terminus, but lacks the
regulatory C-terminus, which contains two highly conserved inhibitory
phosphorylation sites. We observed that the protein product of tv202 assembled a
constitutively active myosin phosphatase uninhibited by kinases such as Zipk.
Thus, we propose that Mypt1-202 plays an important role in maintaining baseline
Mlc2 dephosphorylation and actomyosin relaxation during early zebrafish
development.
PMID- 29960070
TI - MiR-361-5p inhibits the mobility of gastric cancer cells through suppressing
epithelial-mesenchymal transition via the Wnt/beta-catenin pathway.
AB - MiR-361-5p has been reported to be dysregulated in several types of cancers.
However, the function of miR-361-5p in gastric cancer (GC) is still not clear. In
our present study, we aimed to investigate the effects of miR-361-5p in the
mobility of GC and its potential mechanism. We found that miR-361-5p was
significantly decreased in GC cell lines and tumor tissues. Decreased miR-361-5p
expression was correlated with larger tumor size and advanced TNM stage.
Functional analysis revealed that overexpression of miR-361-5p inhibited cell
proliferation and mobility through suppressing the expression of MMP-3, MMP-9 and
VEGF. Moreover, the expression of epithelial marker E-cadherin was increased
while the expression of mesenchymal marker (Snail, N-cadherin, b-catenin) and
Wnt/beta-catenin pathway related proteins (TCF4, Cyclin-D1, c-Myc) was increased
by overexpression of miR-361-5p, indicating that overexpression of miR-361-5p
suppressed epithelial-mesenchymal transition (EMT) via inhibiting Wnt/beta
catenin pathway in GC cells. In order to further verify our conjecture that miR
361-5p mimic inhibited cell mobility through suppressing EMT via Wnt/beta-catenin
pathway in GC, the Wnt/beta-catenin pathway activator LiCl was used in this
study. Our data showed that activation of Wnt/beta-catenin pathway by LiCl
counteracted the regulating roles of miR-361-5p mimic through promoting EMT and
cell mobility. In addition, TCF4 was knockdown and overexpressed in GC cells, and
the results convinced the involvement of Wnt pathway in the regulation of EMT.
Finally, results from in vivo experiments suggested that overexpression of miR
361-5p suppressed tumor growth and the expression of VEGF markedly through
inhibiting EMT via the Wnt/beta-catenin pathway in GC nude mice. Taken together,
our in vitro and in vivo experiments indicated that miR-361-5p suppressed cell
mobility in GC through the inhibition of EMT via Wnt/beta-catenin pathway. Our
findings indicated that miR-361-5p could be a promising therapeutic target for GC
treatment.
PMID- 29960071
TI - A comprehensive genome-wide analysis of the long noncoding RNA expression profile
in metastatic lymph nodes of oral mucosal melanoma.
AB - BACKGROUND & AIM: Oral mucosal melanoma (OMM) is a kind of malignancy with
extremely rare morbidity. It exhibits a poorer biological behavior and clinical
outcome compared with cutaneous melanoma. lncRNAs are endogenous cellular RNA
transcripts with no protein-coding potential and are associated with oncogenesis
through cis- or trans-acting mechanisms. Despite increased evidence that proved
lncRNAs have vital roles in tumorigenesis of mucosal melanoma, little is known
about their functions in the progress of lymph node dissemination of OMM. METHOD:
Here, we constructed a lncRNA and mRNA microarray using six metastatic lymph
nodes and paired-matched non-metastatic lymph nodes. Then, we performed RT-PCR to
validate the microarray data both in primary and metastases. We further
constructed lncRNA and mRNA co-expressing networks and analyzed the biological
functions by Gene Ontology (GO) and pathway analyses for dysregulated lncRNAs and
mRNAs. Cis- and trans-regulation analysis were also performed to explore the
specific mechanism of lncRNAs in OMM. RESULT: Our results showed that 570 lncRNAs
were upregulated with 292 lncRNAs downregulated in the metastatic OMM tissues.
The results of RT-PCR were consistent with our microarray dataset both in primary
and metastases. Gene Ontology (GO) and pathway analyses indicated that they play
an important role in the melanin biosynthetic process, new growing cell tip and
lysosomes in metastatic OMM. In the cis-regulation analysis, we observed
metastasis-associated gene, PLEKHA5, the cis gene of lnc-AEBP2-1_1 and lnc-AEBP2
2_1, and microphthalmia-associated transcription factor (MITF), the cis gene of
SAMMSON_3, SAMMSON_5 and lnc-MITF-5_1. In the trans-regulation analysis, CTBP2
and SUZ12 regulated lncRNA expression in the core TF-lncRNA-gene network.
CONCLUSION: Our results suggest that lncRNAs may be involved in the metastasis of
OMM, and further investigation is needed to focus on the biological functions and
the underlining molecular mechanisms exerted by these dysregulated lncRNAs in
OMM.
PMID- 29960072
TI - Among autophagy genes, ATG16L1 but not IRGM is associated with Crohn's disease in
Iranians.
AB - BACKGROUND: The prevalence of inflammatory bowel diseases is uprising in
countries like Iran. Genetic predisposing elements play prominent role in the
pathogenesis of Crohn's disease. In this study we studied the role of autophagy
genes like IRGM (Immunity related GTPase M) and ATG16L1 (Autophagy related 16
like 1) in the pathogenesis of Crohn's Disease in Iranian patients. METHODS: One
hundred thirty-eight patients and 99 normal controls were recruited in this
study. Polymorphisms in -1644 and -308 upstream of IRGM gene were studied by PCR
sequencing and 20 kb CNVdel/insertion was studied by specific PCR. Rs10065171,
rs4958847 in IRGM gene and rs2241880 in ATG16L1 were studied by Taqman genotyping
assays. RESULTS: None of the so-called predisposing alleles of IRGM gene
predispose Iranians to Crohn's disease while the prevalence of some of them like
CNV deletion was higher in normal controls. Surprisingly all the so-called
predisposing alleles in IRGM were linked to each other (especially rs4958847 with
rs10065172 and polymorphisms in -308 region with rs4958847). Patients harboring A
allele in rs4958847 site showed higher ratio of fibrostenotic type of disease
while in patients with C/T genotype in rs4958847, colonic involvement was seen
more frequently. G allele in ATG16L1 was associated with Crohn's disease though
it was not associated with any phenotypic manifestation. CONCLUSION: In our study
the association of ATG16L1 to Crohn's disease in Iranian patients was confirmed
while it was shown that the studied polymorphisms in IRGM was not associated with
Crohn's disease. Therefore in order to have a better picture about the genetics
of Crohn's disease in Iranian patients, it is recommended to study other
clinically effective polymorphisms in IRGM and ATG16L1 in addition to other genes
which are responsible for the process of autophagy.
PMID- 29960073
TI - Characterization of four new mitogenomes from Ocypodoidea & Grapsoidea, and
phylomitogenomic insights into thoracotreme evolution.
AB - Four new complete mitochondrial genomes (mitogenomes) from the two superfamilies
Ocypodoidea and Grapsoidea were sequenced, which represented Uca (Gelasimus)
borealis (Ocypodidae: Ucinae), Dotilla wichmani (Dotillidae), Metopograpsus
quadridentatus (Grapsidae: Grapsinae), and Gaetice depressus (Varunidae:
Gaeticinae). All of the mitogenomes shared the complete set of 37 mitochondrial
genes. Mitogenome lengths were 15,659, 15,600, 15,517, and 16,288 bp,
respectively, with A + T contents of 69.41%, 68.46%, 70.30%, and 72.96%,
respectively. Comparative genomic analyses suggested that they exhibited
different genomic rearrangements. In particular, G. depressus shared a major
rearrangement pattern present in Eriocheir crabs, while the remainder shared the
brachyuran ground genomic rearrangement patterns. Phylomitogenomic inferences
provided new evidence for the strongly supported nesting of Thoracotremata within
Heterotremata clades. A close phylogenetic relationship was observed between
Varunidae and Macrophthalmidae crabs, and between Dotillidae and Grapsidae crabs,
which was consistent with mitochondrial genomic rearrangement similarities.
Altogether, these results suggest the presence of reciprocal paraphyly for
Ocypodoidea and Grapsoidea.
PMID- 29960074
TI - Comparison of two complete mitochondrial genomes from Perlodidae (Plecoptera:
Perloidea) and the family-level phylogenetic implications of Perloidea.
AB - To obtain a better understanding of the mitochondrial genome in Perlodidae and
the phylogeny of Perloidea, we sequenced two perlodid mitochondrial genomes and
present comparative analyses in the family Perlodidae. Our results show that
genome organization, base composition, codon usage and non-coding and overlapping
regions, the sequences of mitochondrial transcription termination factor (DmTTF)
and structural elements in control region were conserved in Perlodidae. The
unique non-coding regions in COI-trnL2 and trnL2-COII were present in Perlodidae
but were incomplete or absent from other stoneflies, and we also discuss the
conservative property of the sequences between trnE and trnF, trnS1 and ND1. The
secondary structure of tRNAs showed that the trnK, trnP, trnS1 and trnW were
identical and the trnS1 could not be folded into typical secondary structure due
to its absence of DHU arm. Phylogenetic implications supported that
Chloroperlidae is a sister group to Perlodidae and the Perlidae is a sister group
to the clade Chloroperlidae + Perlodidae. This study contributes to understanding
the comparative mitogenomic analysis of Perlodidae and phylogenetic relationships
within the Perloidea.
PMID- 29960075
TI - Effects of dispatcher-assisted bystander cardiopulmonary resuscitation on
neurological recovery in paediatric patients with out-of-hospital cardiac arrest
based on the pre-hospital emergency medical service response time interval.
AB - OBJECTIVES: We investigated the effect of bystander cardiopulmonary resuscitation
(BCPR) with dispatcher assistance (DA) on neurological outcomes based on the
response time interval (RTI) of the pre-hospital emergency medical service (EMS)
among paediatric patients with out-of-hospital cardiac arrest (OHCA). METHODS:
This retrospective registry study was conducted on paediatric patients (<19 years
old) with OHCA who were assessed by EMS providers between 2012 and 2016. The
primary outcome was good neurological recovery based on BCPR with or without DA
and the EMS RTI. Differential effects of BCPR with DA based on the EMS RTI were
analysed by multivariable logistic regression analysis with interaction terms.
RESULTS: Adjusted odds ratios (AORs) and corresponding 95% confidence intervals
(95% CIs) for good neurological recovery were 2.22 (1.27-3.88) for BCPR with DA
and 1.51 (0.77-2.97) for BCPR without DA compared to no BCPR. The faster EMS RTI
group (<5 min) had better neurological recovery than the later EMS RTI group (>=5
min) (AOR: 1.87 [1.04-3.29]). The AORs for good neurological recovery following
BCPR with DA based on the EMS RTI were 2.52 (0.91-6.97) in the faster EMS RTI
group and 2.17 (1.13-4.19) in the later EMS RTI group compared to the no BCPR
group. CONCLUSION: BCPR with DA and a faster EMS RTI were significantly
associated with good neurological recovery in paediatric patients with OHCA. When
the EMS RTI was delayed, the association of BCPR with DA with good neurological
recovery was preserved in paediatric patients with OHCA.
PMID- 29960076
TI - Building Community Support Using a Modified World Cafe Method for Pregnant and
Parenting Teenagers in Forsyth County, North Carolina.
AB - STUDY OBJECTIVE: To identify community priorities, foster awareness of existing
supports, and recognize barriers and opportunities to enhance support services
for pregnant and parenting teens (PPTs). DESIGN AND SETTING: A modified World
Cafe event incorporated parallel, rotating focus groups with semistructured, case
based discussions of salient issues. The event was organized and took place in
Forsyth County, North Carolina. PARTICIPANTS: Seventy-eight local health and
social service professionals and 15 PPT representatives. INTERVENTIONS AND MAIN
OUTCOME MEASURES: Qualitative coding was used to thematically analyze transcript
data. Quantitative data pre-/post-event comparisons were made using Fisher exact
test. RESULTS: Key community-based support services for PPTs were identified.
Qualitative analysis yielded 10 key codes regarding barriers and opportunities to
enhance community-based support services, resulting in 4 themes. Themes included
maximizing access and efficient delivery of high-quality health care, engaging a
3-generation approach to meet the current and future needs of at-risk families,
focusing efforts to meet the unique needs of each teen and his/her family, and
emphasizing teen self-advocacy. Pre/post survey responses were overwhelmingly
positive regarding use of the modified World Cafe format for discussion and
network building. CONCLUSION: The modified World Cafe Method offered a platform
to collaboratively identify challenges and opportunities and to develop networks
to improve health and well-being of PPTs. Engaging multiple stakeholders in
meaningful dialogue might foster multidisciplinary, cross-sector collaboration
that mitigates risk and enhances resilience among PPTs and their children.
PMID- 29960077
TI - The effect of the cerclage wire in the treatment of subtrochanteric femur
fracture with the long proximal femoral nail: A review of 52 cases.
AB - INTRODUCTION: To present the effect of the cerclage fixation, which was performed
for the purpose of preserving the alignment obtained by open reduction, on the
long-term clinical and radiological results of subtrochanteric fractures.
MATERIALS AND METHODS: The inclusion criterias were at least 2 years of follow
up, no severe cognitive impairment, and to be able to walk independently prior to
fracture. Patients with transverse or short oblique subtrochanteric hip fractures
(AO/OTA class 32-A3.1), patients underwent previous femoral or hip operation for
the same side and those with segmental fractures, bilateral fractures and
pathological fractures were not included in the study. The clinical and
radiological results of the patients were evaluated. The clinical evaluations
were performed with Palmer and Parker Mobility Score (PPM), Lower Extremity
Functional Score (LEFS), visual analogue score (VAS) and return to pre-injury
activity status. The elapsed time between the trauma and the surgery date, the
duration of surgery the estimated amount of bleeding, and the length of hospital
stay of patients were assessed. RESULTS: Thirty-two of the 52 patients were
female and 20 were male. The mean age of females was 77.80 +/- 9.75 years and the
mean age of the males was 79.18 +/- 6.50 years. The mean follow-up period of the
patients was 62.25 +/- 34.68 months. The mean time until the patients' surgery
was 6.18 +/- 3.32 days. The mean duration of surgery was 52.6 +/- 13.8 min. The
mean amount of bleeding was 176 +/- 90 ml. The mean length of patients' hospital
stay was 6.2 +/- 3.2 days. The postoperative mean duration of union was found to
be 3.8 +/- 1.6 months. The mean value of varus/valgus angulation in coronal plane
measurements was 0.52 degrees . No complication was observed in any patient
during the cerclage application. The mean number of wire was 1.3. LEFS difference
was statistically significant. PPM decline was not statistically significant.
CONCLUSION: Open reduction and the use of cerclage did not produce a negative
effect in terms of fracture union. The generation of medial support by anatomical
reduction of the fracture prevents the implant failure and provide a basis for
union.
PMID- 29960078
TI - Towards better prediction of Mycobacterium tuberculosis lineages from MIRU-VNTR
data.
AB - The determination of lineages from strain-based molecular genotyping information
is an important problem in tuberculosis. Mycobacterial interspersed repetitive
unit-variable number tandem repeat (MIRU-VNTR) typing is a commonly used
molecular genotyping approach that uses counts of the number of times pre
specified loci repeat in a strain. There are three main approaches for
determining lineage based on MIRU-VNTR data - one based on a direct comparison to
the strains in a curated database, and two others, on machine learning algorithms
trained on a large collection of labeled data. All existing methods have
limitations. The direct approach imposes an arbitrary threshold on how much a
database strain can differ from a given one to be informative. On the other hand,
the machine learning-based approaches require a substantial amount of labeled
data. Notably, all three methods exhibit suboptimal classification accuracy
without additional data. We explore several computational approaches to address
these limitations. First, we show that eliminating the arbitrary threshold
improves the performance of the direct approach. Second, we introduce RuleTB, an
alternative direct method that proposes a concise set of rules for determining
lineages. Lastly, we propose StackTB, a machine learning approach that requires
only a fraction of the training data to outperform the accuracy of both existing
machine learning methods. Our approaches demonstrate superior performance on a
training dataset collected in New York City over 10 years, and the improvement in
performance translates to a held-out testing set. We conclude that our methods
provide opportunities for improving the determination of pathogenic lineages
based on MIRU-VNTR data.
PMID- 29960079
TI - Cousins at work: How combining medical with optical imaging enhances in vivo cell
tracking.
AB - Microscopy and medical imaging are related in their exploitation of
electromagnetic waves, but were developed to satisfy differing needs, namely to
observe small objects or to look inside subjects/objects, respectively. Together,
these techniques can help elucidate complex biological processes and better
understand health and disease. A current major challenge is to delineate
mechanisms governing cell migration and tissue invasion in organismal
development, the immune system and in human diseases such as cancer where the
spatiotemporal tracking of small cell numbers in live animal models is extremely
challenging. Multi-modal multi-scale in vivo cell tracking integrates medical and
optical imaging. Fuelled by basic research in cancer biology and cell-based
therapeutics, it has been enabled by technological advances providing enhanced
resolution, sensitivity and multiplexing capabilities. Here, we review which
imaging modalities have been successfully used for in vivo cell tracking and how
this challenging task has benefitted from combining macroscopic with microscopic
techniques.
PMID- 29960080
TI - Trabecular bone microarchitecture predicts fragility fractures in postmenopausal
women on denosumab treatment.
AB - BACKGROUND: High-resolution peripheral quantitative computed tomography (HR-pQCT)
represents a three-dimensional tool for the screening of osteoporosis patients
i.e., regarding fracture risk. The purpose of this study was to determine the
baseline and follow-up bone microarchitecture in relation to incident fracture
risk in postmenopausal women on denosumab treatment. METHODS: We have
retrospectively evaluated data from 182 postmenopausal women treated with
denosumab that underwent an initial HR-pQCT scan before the initiation of the
treatment; and at least one second HR-pQCT after 12 months. Women were assigned
to two groups based on documented fragility fractures for the following 2.9 +/-
1.1 years: fracture (n = 22) and no fracture (n = 160). Baseline parameters from
DXA, HR-pQCT and bone turnover were compared between the two groups. Furthermore,
ROC and multiple regression analyses of the baseline and follow-up data were
performed to evaluate the predictive value regarding incident fractures. RESULTS:
At baseline, trabecular parameters were significantly reduced in the fracture
group and showed the best predictive value for new fractures, while DXA results
could not predict fractures. A multiple regression model identified BV/TV and age
as the best baseline parameters for incident fracture risk. At 12 months,
cortical and trabecular parameters increased in the non-fracture group, while no
significant increase was noted in the fracture group. However, no significant
differences regarding the changes of these parameters could be detected between
the non-fracture and fracture cohort. CONCLUSIONS: Trabecular bone microstructure
at baseline is crucial for incident fracture risk in postmenopausal women on
denosumab treatment, especially in comparison to DXA values. In this context, the
microstructural follow-up results seemed to be of lesser importance regarding
fracture risk. The results of this exploratory study should be validated in
independent populations.
PMID- 29960081
TI - Cumulative radiation exposure from medical imaging and associated lifetime cancer
risk in children with osteogenesis imperfecta.
AB - OBJECTIVES: To estimate the cumulative effective dose of radiation (E) and
additional lifetime attributable risk (LAR) of cancer from ionizing radiation in
children with osteogenesis imperfecta (OI), who require frequent imaging for
fractures and bone densitometry (DXA) surveillance. Also, to evaluate the pattern
of long bone fractures. METHODS: We reviewed all imaging (x-rays, DXA and
computed tomography [CT]) conducted in a cohort of children with OI with a
minimum observation period of 5 years. For each image, E was estimated using age
dependent local data, and LAR of cancer was extrapolated. LAR and fracture data
were compared among children with mild, moderate and severe OI. LAR was allocated
to cancer risk categories, and the moderate risk group (1 in 1000 to 1 in 100)
was evaluated further. RESULTS: Results from 106 children with OI (50% females,
5747 images) are presented, with a median (range) observation period of 11.7 (5.2
15.6) years. CT accounted for 0.8% of total imaging procedures but contributed to
66% of total E. The overall LAR of cancer was minimal, averaging an additional
8.8 cases per 100,000 exposed patients (0.8-403). LAR was significantly lower in
children with mild OI compared to those with moderate (p = 0.006) and severe OI
(p = 0.001). All patients with a moderate LAR of cancer (n = 8) had undergone CT
scans and 88% had scoliosis or vertebral fractures. The cohort experienced 412
long bone fractures, with the most common site being the femur (26.5%). OI
severity correlated positively with long bone fracture rates (p < 0.001).
CONCLUSIONS: When compared to baseline LAR of cancer (50%) the additional cancer
risk from ionizing radiation imaging in our paediatric OI cohort was small
(0.0088%). To reduce additional cancer risk, we recommend replacing spinal x-rays
with vertebral fracture assessments on DXA and exercising caution with CT
imaging.
PMID- 29960082
TI - Monitoring changing cellular characteristics during the development of a fin cell
line from Cyprinus carpio.
AB - The establishment and in-depth characterization of a novel continuous cell line
derived from fin tissue of common carp (Cyprinus carpio), CCApin, is reported.
The cells of the cell line could be propagated in Leibovitz's L-15 medium
containing 15% foetal calf serum and 0.5% carp serum for >150 passages during the
last 24 months, with a stable fast growth. Furthermore, antibody staining
indicated that cell types obtained in primary cultures, containing the epithelial
stem-cell marker tumorprotein 63, were different from cells in long-term cell
cultures, containing tight junction protein zona occludens 1 and cytokeratin 7.
These observations suggest a switch of dominant cell types. Molecular analysis of
gene expression profiles of caudal fin tissue and CCApin cells showed that genes
relevant in epithelial cells but also in mesenchymal cells were expressed.
However, during cultivation of CCApin a set of very steadily expressed, primarily
mesenchymal genes like collagen 1 alpha 1, fibronectin or cadherin 2 was found.
In summary, the long-term cell culture could be described as a stably growing
epithelial population with some mesenchymal features. There are several
application possibilities, especially for virus susceptibility studies, e.g.
cyprinid herpesvirus-3 (CyHV-3). The study leads to a better understanding of
molecular and physiological mechanisms of in vitro fish cell cultures.
PMID- 29960083
TI - Epidemiology and risk factors associated with Anaplasma marginale infection of
cattle in Peninsular Malaysia.
AB - Bovine anaplasmosis is a major concern to cattle farming in most parts of the
world. Anaplasmosis negatively impacts the profitability of cattle farming by
reducing the production, reproduction, and draft ability of cattle. Here, we
report results from a one-year cross sectional study to determine the
epidemiology and the risk factors for Anaplasma marginale infection of cattle in
Peninsular Malaysia. Examination of one thousand and forty five blood samples of
apparently healthy cattle from forty-three farms in all the states of Peninsular
Malaysia by polymerase chain reaction (PCR) assay revealed an overall prevalence
of A. marginale infection of cattle of 72.6%, showing high endemicity of this
heamoprotozoan among cattle in the country. Cattle breeds, production type, herd
owner, herd size, management system, farm size, farm age, prophylactic treatment
against blood parasites, presence of ticks, frequency of deticking, zones,
closeness to forest, closeness to waste area, closeness to human settlement and
closeness to body of water were the risk factors significantly associated (P <
0.05) with the detection of A. marginale in cattle. Results of this first
molecular study on the epidemiology and risk factors for A. marginale infection
of cattle from all the states of Peninsular Malaysia suggest policies and
strategies for the prevention and control of the parasite to improve
profitability of cattle farming in the country.
PMID- 29960084
TI - Educational scaffolding: Back to basics for nursing education in the 21st
century.
PMID- 29960085
TI - Developing the social media presence of @NurseEducToday by using Twitter.
PMID- 29960086
TI - New advances in encoding and decoding of brain signals.
PMID- 29960088
TI - High-resolution 3D diffusion tensor MRI of anesthetized rhesus macaque brain at
3T.
AB - Diffusion Magnetic Resonance Imaging (dMRI) has been widely used to investigate
human brain microstructure and connectivity and its abnormalities in a variety of
brain deficits, whether acute, neurodevelopmental or neurodegenerative. However,
the biological interpretation and validation of dMRI data modelling is still a
crucial challenge in the field. In this respect, achieving high spatial
resolution in-vivo dMRI in the non-human primate to compare these observations
both with human dMRI on the one hand and 'ground truth' microstructural and
histological data on the other hand is of outmost importance. Here, we developed
a dMRI pulse sequence based on 3D-multishot Echo Planar Imaging (3D-msEPI) on a
3T human clinical scanner. We demonstrate the feasibility of cerebral dMRI at an
isotropic resolution of 0.5 mm in 4 anesthetized macaque monkeys. The added value
of the high-resolution dMRI is illustrated by focusing on two aspects. First, we
show an enhanced descriptive power of the fine substructure of the hippocampus.
Second, we show a more physiological description of the interface between cortex
grey matter, superficial and deep white matter. Overall, the high spatial
resolution dMRI acquisition method proposed in this study is a significant
achievement with respect to the state of the art of dMRI on anesthetized monkeys.
This study highlights also the potential of very high-resolution dMRI to
precisely capture the microstructure of thin cerebral structures such as the
hippocampus and superficial white matter.
PMID- 29960087
TI - Mapping the topological organisation of beta oscillations in motor cortex using
MEG.
AB - The spatial topology of the human motor cortex has been well studied,
particularly using functional Magnetic Resonance Imaging (fMRI) which allows
spatial separation of haemodynamic responses arising from stimulation of
different body parts, individual digits and even spatially separate areas of the
same digit. However, the spatial organisation of electrophysiological responses,
particularly neural oscillations (rhythmic changes in electrical potential across
cellular assemblies) has been less well studied. Mapping the spatial signature of
neural oscillations is possible using magnetoencephalography (MEG), however
spatial differentiation of responses induced by movement of separate digits is a
challenge, because the brain regions involved are separated by only a few
millimetres. In this paper we first show, in simulation, how to optimise
experimental design and beamformer spatial filtering techniques to increase the
spatial specificity of MEG derived functional images. Combining this result with
experimental data, we then capture the organisation of the post-movement beta
band (13-30 Hz) oscillatory response to movement of digits 2 and 5 of the
dominant hand, in individual subjects. By comparing these MEG results to ultra
high field (7T) fMRI, we also show significant spatial agreement between beta
modulation and the blood oxygenation level dependent (BOLD) response. Our results
show that, when using an optimised inverse solution and controlling subject
movement (using custom fitted foam padding) the spatial resolution of MEG can be
of order 3-5 mm. The method described offers exciting potential to understand
better the cortical organisation of oscillations, and to probe such organisation
in patient populations where those oscillations are known to be abnormal.
PMID- 29960089
TI - Influence of talker discontinuity on cortical dynamics of auditory spatial
attention.
AB - In everyday acoustic scenes, listeners face the challenge of selectively
attending to a sound source and maintaining attention on that source long enough
to extract meaning. This task is made more daunting by frequent perceptual
discontinuities in the acoustic scene: talkers move in space and conversations
switch from one speaker to another in a background of many other sources. The
inherent dynamics of such switches directly impact our ability to sustain
attention. Here we asked how discontinuity in talker voice affects the ability to
focus auditory attention to sounds from a particular location as well as neural
correlates of underlying processes. During electroencephalography recordings,
listeners attended to a stream of spoken syllables from one direction while
ignoring distracting syllables from a different talker from the opposite
hemifield. On some trials, the talker switched locations in the middle of the
streams, creating a discontinuity. This switch disrupted attentional modulation
of cortical responses; specifically, event-related potentials evoked by syllables
in the to-be-attended direction were suppressed and power in alpha oscillations
(8-12 Hz) were reduced following the discontinuity. Importantly, at an individual
level, the ability to maintain attention to a target stream and report its
content, despite the discontinuity, correlates with the magnitude of the
disruption of these cortical responses. These results have implications for
understanding cortical mechanisms supporting attention. The changes in the
cortical responses may serve as a predictor of how well individuals can
communicate in complex acoustic scenes and may help in the development of
assistive devices and interventions to aid clinical populations.
PMID- 29960090
TI - Kinematic alignment of current TKA implants does not restore the native trochlear
anatomy.
AB - INTRODUCTION: Preserving constitutional patellofemoral anatomy, and thus
producing physiological patellofemoral kinematics, could prevent patellofemoral
complications and improve clinical outcomes after kinematically aligned TKA (KA
TKA). Our study aims 1) to compare the native and prosthetic trochleae (planned
or implanted), and 2) to estimate the safety of implanting a larger Persona(r)
femoral component size matching the proximal lateral trochlea facet height
(flange area) in order to reduce the native articular surfaces understuffing
generated by the prosthetic KA trochlea. METHODS: Persona(r) femoral component 3D
model was virtually kinematically aligned on 3D bone-cartilage models of healthy
knees by using a conventional KA technique (group 1, 36models, planned KA TKA) or
an alternative KA technique (AT KA TKA) aiming to match the proximal (flange
area) lateral facet height (10 models, planned AT KA TKA). Also, 13postoperative
bone-implant (KA Persona(r)) models were co-registered to the same coordinate
geometry as their preoperative bone-cartilage models (group 2implanted KA TKA).
In-house analysis software was used to compare native and prosthetic trochlea
articular surfaces and medio-lateral implant overhangs for every group. RESULTS:
The planned and performed prosthetic trochleae were similar and valgus oriented
(6.1 and 8.5, respectively), substantially proximally understuffed compared to
the native trochlea. The AT KA TKAs shows a high rate of native trochlea surface
overstuffing (70%, 90%, and 100% for lateral facet, groove, medial facet) and
mediolateral implant overhang (60%). There was no overstuffing with conventional
KA TKAs having their anterior femoral cut flush. CONCLUSION: We found that with
both the planned and implanted femoral components, the KA Persona(r) trochlea was
more valgus oriented and understuffed compared to the native trochlear anatomy.
In addition, restoring the lateral trochlea facet height by increasing the
femoral component size generated a high rate of trochlea overstuffing and
mediolateral implant overhang. While restoring a native trochlea with KA TKA is
not possible, the clinical impact of this is low, especially on PF complications.
In current practice it is better to undersize the implants even if it does not
restore the native anatomy. Longer follow-up is needed for KA TKAs performed with
current implant, and the debate of developing new, more anatomic, implants
specifically designed for KA technique is now opened. LEVEL OF EVIDENCE: II,
Laboratory controlled study.
PMID- 29960091
TI - Isolated arthroscopic Bankart repair vs. Bankart repair with "remplissage" for
anterior shoulder instability with engaging Hill-Sachs lesion: A meta-analysis.
AB - INTRODUCTION: Arthroscopic "remplissage" of a Hill-Sachs lesion (HSL) associated
with a Bankart repair (BR) has been recently introduced as a surgical option to
treat chronic anterior shoulder instability. The purpose of this study was to
analyze the current literature comparing results of isolated BR versus
BR+remplissage in the treatment of anterior shoulder instability with engaging
HSL. HYPOTHESIS: BR+remplissage are superior to isolated BR in the management of
anterior shoulder instability with engaging HSL. MATERIAL AND METHODS: Four
electronic databases were searched for original, English-language studies
comparing BR vs. BR+remplissage procedures. During the inclusion process we used
international Preferred Reporting Items for Systematic review and Meta-Analysis
(PRISMA) guidelines and the Strengthening the Reporting of Observational Studies
in Epidemiology (STROBE) checklist. Our data were extracted from the text, tables
and figures of the selected studies. RESULTS: Three comparative studies were
identified, which included 146 patients; 74 of them underwent isolated BR, and 72
BR+remplissage procedure. The isolated BR results in significantly higher risk of
recurrence and redislocation. There was no significant difference in the rates of
reoperation and time to return to sport between the two procedures. Rowe and UCLA
scores were lower in the isolated BR group compared with the BR+remplissage
group. DISCUSSION: This meta-analysis demonstrates the superiority of
BR+remplissage procedure vs. isolated BR in the management of anterior shoulder
instability with engaging HSL and with up to 25% glenoid bone loss regarding
redislocation rate, recurrent instability and functional scores. A comparison
between postoperative range of motion and particularly external rotation was not
able to be formally assessed in this study. LEVEL OF EVIDENCE: III.
PMID- 29960092
TI - Responses of antioxidant and biotransformation enzymes in Carassius carassius
exposed to hexabromocyclododecane.
AB - The ubiquitous existence of hexabromocyclododecane (HBCD) in environmental
matrices has made it attractive to both field investigators as well as laboratory
researchers. However, literature on the biological effects caused by HBCD on
aquatic vertebrates seldom exist. This has inevitably increased the difficulty of
toxicological assessment in the aquatic environment. Juvenile crucian carp
(Carassius carassius) were exposed (flow-through) to different concentrations of
technical HBCD (nominal 2, 20, 200 MUg L-1) for 7 days to determine the responses
of antioxidant and biotransformation enzymes. HBCD was found to be increasingly
bioconcentrated in the fish livers as time proceeds. Also, the contribution of
alpha-HBCD exhibited an enhancement from 13% in the exposure solutions to 24% in
crucian carp, still much lower than in wild fishes (ca. 80%). HBCD induced
activities of antioxidant enzymes in most cases, as well as increased level of
lipid peroxidation. In contrast to the weak response of 7-ethoxyresorufin-O
deethylase (EROD), 7-pentoxyresorufin-O-depentylase (PROD) activity was generally
induced in a time-dependent manner with peaks at day 2. Phase II enzyme
Glutathione-S-transferase (GST) showed a dose-dependent induction with maximums
in the 20 MUg L-1 treatment at all the four timepoints of 1, 2, 4 and 7 days.
Some enzymatic responses showed good associations, indicating coordinated
functions. To sum up, tHBCD exposure in the present circumstance had produced an
ecological stress to crucian carp. The low levels of biotransformation and slow
rates of bioisomerization suggest a possible long-term toxic effect, especially
around HBCD point sources.
PMID- 29960093
TI - Management of Recurrent Glossopharyngeal Neuralgia Following Microvascular
Decompression Surgery.
AB - BACKGROUND: Glossopharyngeal neuralgia (GPN) is a rare condition, commonly
misdiagnosed as trigeminal neuralgia. Microvascular decompression (MVD) is
considered the first line of treatment in medically refractive idiopathic GPN,
and the recurrence rate is reported to be 7.1%. We present our first case report
on the surgical management of a patient with recurrent GPN and analyze the
possible causes for recurrence after MVD. CASE DESCRIPTION: A 73-year-old
gentleman was referred to us with a diagnosis of recurrent left GPN. He was
diagnosed 6 years ago with left mandibular branch trigeminal neuralgia for the
complaint of left-side tongue pain. He received left mandibular nerve block twice
earlier and Gamma Knife radiotherapy 2 years ago without relief. A year ago he
was diagnosed with GPN by a neurosurgeon, and MVD was performed. The posterior
inferior cerebellar artery and vertebral artery were the offending vessels and
were interposed with Teflon. After a temporary pain relief, the patient had a
recurrence. Redo-MVD with transposition of the vertebral artery and further
interposition of posterior inferior cerebellar artery did not help. After
referral to us, we operated on the patient again and found 2 small arteries at
the root entry zone (REZ). Interposition with Teflon and splitting of the
rootlets relieved the pain. CONCLUSIONS: MVD is considered the first line of
treatment in drug-resistant idiopathic GPN. Thorough exploration of REZ for small
arteries and veins is mandatory to prevent recurrence. Vascular compression can
occur at the cisternal portion or at the REZ. In recurrent cases, splitting of
the glossopharyngeal nerve rootlets adds to the good outcome.
PMID- 29960094
TI - Stereotactic Brachytherapy with Iodine-125 Seeds Plus Temozolomide Induced
Complete and Durable Remission in a Patient with Recurrent Primary Central
Nervous System Lymphoma.
AB - BACKGROUND: The optimal treatment of recurrent primary central nervous system
lymphoma (PCNSL) has not yet been determined. We report a patient with recurrent
PCNSL who has been successfully treated with stereotactic brachytherapy (SBT)
with iodine-125 seeds plus temozolomide (TMZ). CASE DESCRIPTION: A 51-year-old
man who underwent left occipital lobe tumor resection 11 years earlier presented
with a 1-month history of right hand weakness. Magnetic resonance imaging (MRI)
revealed a recurrent PCNSL, which was confirmed by pathological examination. He
was treated with SBT plus TMZ. At 1 month after surgery, a repeat MRI revealed
nearly complete disappearance of the lesion. At 13.5 months postsurgery, the
patient was neurologically intact except for right homonymous hemianopia, and
follow-up MRI did not reveal a recurrent tumor. CONCLUSIONS: To our knowledge,
this is the first case of recurrent PCNSL successfully treated with SBT plus TMZ.
Further randomized studies are needed to confirm the therapeutic impact of this
new method.
PMID- 29960095
TI - Endoscopically Assisted Targeted Keyhole Retrosigmoid Approaches for
Microvascular Decompression: Quantitative Anatomic Study.
AB - OBJECTIVE: We describe and quantitatively assess minimally invasive keyhole
retrosigmoid approaches targeted to the upper, middle, and lower cranial nerve
(CN) complexes of the cerebellopontine angle (CPA). METHODS: Anatomic dissections
were performed on 10 sides of 5 fixed, silicone-injected cadaver heads. Surgical
views through various trajectories were assessed in endoscopic videos and 3
dimensional (3D) interactive virtual reality microscope views. Surgical freedom
and angles of attack to the proximal and distal areas of CN complexes of the CPA
were compared among upper and lower keyholes and conventional retrosigmoid
craniotomy using neuronavigation. RESULTS: Compared with keyholes, the
conventional approach had superior surgical freedom to most areas except for the
distal CN V, the root of CN VII, and the root of CN IX, where differences were
not significant. The conventional retrosigmoid approach provided a larger
horizontal angle of attack than either the upper or lower keyholes for all
selected areas; however, the vertical angles of attack were not different.
Splitting the petrosal fissure resulted in a significant increase in the vertical
angle of attack to the root zones of CNs V and VII but not to the distal areas of
these nerves or CN IX. Illustrative cases of endoscope-assisted keyhole
retrosigmoid approaches for the treatment of trigeminal neuralgia, hemifacial
spasm, and glossopharyngeal neuralgia are presented. CONCLUSIONS: Targeted
keyhole retrosigmoid approaches require detailed understanding of the 3D anatomy
of the CPA to create appropriate locations of corridors, including skin incisions
and keyholes. Endoscope assistance complements the standard microsurgical
technique by maximizing the visualization and identification of the delicate
neurovascular structures.
PMID- 29960097
TI - Roads and the spread of HIV in Africa.
AB - I here use GIS and HIV data from five African countries to estimate the effect of
road proximity on HIV infection. I find a negative effect of the distance to the
nearest paved road on the probability of being infected with HIV: a one standard
deviation fall in this distance (approximately 2.4 km) increases the probability
of infection by 0.6-2.0 percentage points. Using slope as an instrument for road
distance continues to produce a negative and significant estimated coefficient.
However this relationship may also reflect selection and reverse causality in
individual choice of location, and I extensively discuss the role of migration.
While the number of lifetime sexual partners is significantly influenced by the
presence of roads in some recent years, the effect of road distance on access to
protection has disappeared.
PMID- 29960096
TI - Convection-Enhanced Delivery of Polymeric Nanoparticles Encapsulating
Chemotherapy in Canines with Spontaneous Supratentorial Tumors.
AB - BACKGROUND: Despite aggressive multimodal treatment, survival for patients with
glioblastoma remains dismal. One obstacle to improving patient outcomes is the
difficulty in delivering adequate therapeutic to the central nervous system due
to the presence of the blood-brain barrier. Although direct drug infusion by
convection-enhanced delivery (CED) can bypass the blood-brain barrier and
facilitate delivery to intracranial tumors, determining the distribution of
delivered therapeutic remains problematic. Image guidance is a strategy that can
optimize the accuracy of therapeutic delivery. METHODS: Here we performed an open
label clinical trial in 10 pet dogs with spontaneous intracranial tumors to
examine the target coverage accuracy of delivering polymeric magnetite
nanoparticles (PMNPs) encapsulating temozolomide (TMZ). A modified small animal
frame was applied to the head of each subject, and PMNPs were delivered
stereotactically to the center of the tumor. Magnetic resonance imaging (MRI) was
performed immediately postoperatively to examine PMNP distribution, and the
animals were followed until death. RESULTS: Nine of the 10 dogs underwent PMNP
infusion without complications. No infusate backflow was observed during any
procedure. In 70% of the cases, the infusion accurately targeted the tumor mass,
as determined by the presence of PMNP signal in the tumor on immediate
postoperative MRI. CONCLUSIONS: These data suggest that CED of PMNPs carrying TMZ
is safe in dogs with intracranial tumors and can lead to nanoparticle
distribution in the region of the target. Image guidance is an important adjunct
to CED, because distribution is unpredictable, with the potential for missed
target delivery.
PMID- 29960098
TI - High rate of Clostridium difficile among young adults presenting with diarrhea at
two hospitals in Kenya.
AB - BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of
antibiotic-associated diarrhea worldwide. As a result, the US Centers for Disease
Control and Prevention have designated C. difficile as an urgent threat. Despite
the global public health risk posed by CDI, little is known about its
epidemiology on the African continent. This article describes the common
occurrence of CDI from a cross-section of consecutively seen, randomly enrolled
patients presenting with diarrhea at two major hospitals in Kenya. METHODS:
Patients presenting with diarrhea at two major hospitals in Kenya from May to
July 2017 were enrolled. After signing the informed consent, stool samples,
demographic data, medical history, prior antibiotic use, and HIV status were
obtained from the patients. C. difficile was detected and validated by toxigenic
culture and PCR. RESULTS: The average age of the patients was 35.5 years (range 3
86 years); 59% were male and 41% were female. Out of 105 patient stools tested,
98 (93.3%) were positive for C. difficile by culture. PCR analysis confirmed C.
difficile-specific genes, tcdA, tcdB, and tcdC, in the strains isolated from the
stools. Further, 82.5% of the stools had C. difficile isolates bearing the frame
shift deletion associated with hypervirulent strains. Remarkably, 91.9% of the
stools that tested positive for C. difficile came from patients under 60 years
old, with 64.3% being less than 40 years of age. The majority of the patients
(85%) reported over-the-counter antibiotic use in the last 30days before the
hospital visit. CONCLUSIONS: Together, the results revealed an unusually high
incidence of C. difficile in the stools analyzed, especially among young adults
who are thought to be less vulnerable. Comprehensive research is urgently needed
to examine the epidemiology, risk factors, pathogenesis, comorbidities, clinical
outcomes, antibiotic susceptibility, and genetic makeup of C. difficile strains
circulating on the African continent.
PMID- 29960099
TI - Trx-1 ameliorates learning and memory deficits in MPTP-induced Parkinson's
disease model in mice.
AB - Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic
neurons in the substantia nigra pars compacta (SNpc), characteristic motor
symptoms and cognitive impairment. Thioredoxin-1 (Trx-1) is a redox protein and
protects neurons from various injuries. Our previous study has shown that Trx-1
overexpression attenuates movement disorder in PD. However, whether Trx-1
ameliorates cognitive deficits in PD is still unknown. In the present study, we
investigated the effects of Trx-1 on learning and memory in the 1-methyl-4-phenyl
1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in mice. We demonstrated that
deficits in learning and memory were induced by MPTP in mice through the elevated
plus-maze test. We found that the retention transfer latency time was shorten,
escape latency was decreased and the number of platform crossings was increased
in the Morris water maze (MWM) in Trx-1 transgenic (TG) mice when compared with
wild type mice. The expressions of tyrosine hydroxylase (TH) and dopamine D1
receptor (D1R) were decreased by MPTP, which were restored in Trx-1 TG mice. The
expression of N-methyl-D-aspartate receptor 2B subunit (NR2B), the levels of
phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cAMP
response element binding protein (CREB) in the hippocampus were decreased by
MPTP, which were reversed in Trx-1 TG mice. These results suggest that Trx-1
ameliorates learning and memory deficits in MPTP-induced PD model in mice via
modulating the D1R and the NMDAR-ERK1/2-CREB pathway. Trx-1 may be a therapy
target for learning and memory deficits in PD.
PMID- 29960101
TI - Clinical and genetic features of L1 syndrome patients: Definition of two novel
mutations.
AB - L1 syndrome is a rare X linked recessive disorder caused bygene mutations in the
L1 cell adhesion molecule (L1CAM), and characterized by hydrocephalus,
intellectual disability, adducted thumbs and spasticity of the legs. The gene
encodes a protein which plays an important role in neuronal development. Two
unrelated L1 syndrome cases, with global developmental delay and hydrocephalus,
were referred to pediatric genetics subdivision for genetic counseling. Bilateral
adducted thumbs and spasticity in the lower extremities were also observed in
both patients. Molecular analysis revealed two novel hemizygous mutations in the
patients: a deletion mutation (c.749delG; p.Ser250Thrfs*51) and a splicing
mutation (c.3166+1G>A). To conclude; in male patients with intellectual
disability and hydrocephalus, where adducted thumbs are present, L1 syndrome
should be considered.
PMID- 29960102
TI - Breakthrough treatment with bortezomib for a patient with anti-NMDAR
encephalitis.
AB - After its discovery, anti-N-methyl-d-aspartate receptor encephalitis is now an
established neuroinflammatory disorder, for which various immune-suppressive
strategies have been successfully proposed. The most commonly applied therapy
includes high dose cortico-steroids, as well as plasma exchange procedures
(PLEX), and subsequently either oral immunosuppressants, such as azathioprine or
B-cell depletion by the anti- CD20 monoclonal antibody rituximab. However, in
rare cases we are faced with patients who do not respond to either oral
immunosuppressants, or rituximab. Hence, we have recently described bortezomib, a
proteasome inhibitor as a potentially effective treatment in patients not
responding to first-line immune-therapies. Particularly, plasma cells as mature,
non-dividing antibody secreting cells are highly sensitive to proteasome
inhibitors. Here, we report of a patient with severe, and prolonged anti-NMDAR
encephalitis despite PLEX and repeatedly applied high dose rituximab. As
documented in the accompanying video that shows the different stages before, and
immediately after bortezomib therapy the patient recovered swiftly.
PMID- 29960103
TI - Utility of CT angiography in screening for traumatic cerebrovascular injury.
AB - OBJECTIVE: Computed tomographic angiography (CTA) is increasingly utilized to
evaluate for traumatic cerebrovascular injury (TCVI). The purpose of this study
was to determine the yield, management effect, and risk of stroke or poor outcome
of a positive CTA in a large cohort of trauma patients. PATIENTS AND METHODS: A
retrospective analysis was performed on 1290 consecutive trauma patients that
underwent head and/or neck CTA at our level I trauma center from 2006 to 2015.
Clinical variables assessed include mechanism of injury, neurological status, CTA
findings, subsequent imaging results, patient management, and clinical outcomes.
RESULTS: Among 1290 patients who underwent CTA, 200 (15.5%) were positive for
TCVI, higher in blunt than penetrating trauma patients. In a generalized linear
model, factors that increased likelihood of positive CTA included multiple
cervical fractures, fractures with foraminal involvement, gunshot injury, Glasgow
Coma Scale <= 13, and focal neurological deficit. Excluding cases with these
factors lowered the positive rate to 4.3%. Of the 200 CTA-positives, 99 were
treated for TCVI and 9 (4.5%) developed a subsequent stroke as compared to 5
(0.5%) in CTA-negative patients (odds ratio 10.2, Fisher exact test, p < 0.001).
Risk of death or nursing facility discharge location was also higher in CTA
positive patients, correcting for age and presenting GCS (p < 0.01). CONCLUSION:
CTA had a modest yield in identifying TCVI in this cohort. When positive, CTA
influenced management and predicted an increased risk of subsequent stroke and
poor outcome.
PMID- 29960104
TI - Reality orientation therapy benefits cognition in older people with dementia: A
meta-analysis.
AB - BACKGROUND/AIMS: To investigate the effect of reality orientation therapy on
cognition, behavioral problems, and depressive symptoms in older people with
dementia. DESIGN: Meta-analysis of randomized controlled trials (RCTs). DATA
SOURCE: Various electronic databases were searched to select eligible articles,
which included CINAHL, Embase, Pubmed, ProQuest, PsycINFO, the Cochrane Central
Register of Controlled Trials, Google Scholar and Chinese electronic databases
comprising Chinese Electronic Periodical Services and China Knowledge Resource
Integrated. REVIEW METHODS: Two reviewers independently extracted data and
evaluated the methodological quality of the included articles. All analyses were
performed using a random-effects model. Moderator analyses were conducted to
identify the superior subgroup of intervention details that benefited from
reality orientation therapy. RESULTS: There was an overall random effect of
reality orientation therapy of improving cognitive functions (n = 11, g = 0.39,
95% confidence interval [CI] = 0.25, 0.53); however, reality orientation therapy
did not ameliorate behavioral problems (n = 5, g= -0.18, 95% CI= -0.36, 0.00) and
depressive symptoms (n = 5, g= -0.17, 95% CI= -0.39, 0.05). A subgroup analysis
revealed that studies of reality orientation therapy alone had a greater
improvement in cognitive functions compared to those studies adopting reality
orientation therapy combined with other types of techniques, but the difference
in effect sizes between the two approaches was not significant (g = 0.51 vs.
0.35, p = 0.333). CONCLUSIONS: Reality orientation therapy can be considered
routine care for the maintenance and improvement of cognitive functions in older
populations with dementia. Health professionals and caregivers can be further
educated and trained to regularly perform reality orientation therapy to improve
the cognition of older people with dementia.
PMID- 29960105
TI - Efficacy of facilitated tucking combined with non-nutritive sucking on very
preterm infants' pain during the heel-stick procedure: A randomized controlled
trial.
AB - BACKGROUND: Reducing acute pain in premature infants during neonatal care
improves their neurophysiological development. The use of pharmacological and non
pharmacological analgesia, such as sucrose, is limited per day, particularly for
very preterm infants. Thus, the usual practice of non-nutritive sucking is often
used alone. Facilitated tucking could be an additional strategy to non-nutritive
sucking for reducing pain. To the best of our knowledge, no randomized trial has
compared the combination of facilitated tucking and non-nutritive sucking to non
nutritive sucking alone. OBJECTIVES: To compare the efficacy of facilitated
tucking in combination with non-nutritive sucking (intervention group) to non
nutritive sucking alone (control group) in reducing pain during the heel-stick
procedure in very preterm infants. DESIGN: Prospective, randomized controlled
trial. SETTINGS: Level III and II neonatal care units, including the neurosensory
care management program. METHODS: Very preterm infants (gestational age between
28 and 32 weeks) were randomly assigned by a computer programme to the
intervention or control group during a heel-stick procedure within the first 48 h
of life. In both groups, infants were placed in an asymmetric position on a
cushion; noise and light were limited following routine care. A heel-stick was
performed first in the care sequence. In the intervention group, facilitated
tucking was performed by a nurse or nursing assistant. The procedure was video
recorded from 15 s (T-15 s) before the procedure until three minutes (T + 3 min)
after the end of the procedure. Pain was blindly assessed by two independent
specialist nurses. The primary outcome was the pain score evaluated 15 s before
the procedure and 30 s immediately after by the premature infant pain profile
(PIPP) scale. The secondary outcome was the pain score evaluated between T-15 s
and T + 3 min by the DAN scale (a French acronym for the acute pain of a
newborn). RESULTS: Sixty infants were included (30 in each group). The PIPP pain
scores did not differ between the intervention group (median: 8.0; interquartile
range (IQR): 6.0-12.0) and the control group (median: 9.5; IQR: 7.0-13.0, p =
0.32). Pain assessed by the DAN scale at T + 3 min was lower in the intervention
group than in the control group (median: 0.3; IQR: 0.0-1.0 and 2.0; IQR: 0.5-3.0,
respectively, p = 0.001). CONCLUSIONS: The combined use of facilitated tucking
and non-nutritive sucking did not significantly alleviate pain during the heel
stick procedure. However, the addition of facilitated tucking facilitated faster
pain recovery following the heel-stick procedure.
PMID- 29960106
TI - Molecular Mechanisms of Leaf Morphogenesis.
AB - Plants maintain the ability to form lateral appendages throughout their life
cycle and form leaves as the principal lateral appendages of the stem. Leaves
initiate at the peripheral zone of the shoot apical meristem and then develop
into flattened structures. In most plants, the leaf functions as a solar panel,
where photosynthesis converts carbon dioxide and water into carbohydrates and
oxygen. To produce structures that can optimally fulfill this function, plants
precisely control the initiation, shape, and polarity of leaves. Moreover, leaf
development is highly flexible but follows common themes with conserved
regulatory mechanisms. Leaves may have evolved from lateral branches that are
converted into determinate, flattened structures. Many other plant parts, such as
floral organs, are considered specialized leaves, and thus leaf development
underlies their morphogenesis. Here, we review recent advances in the
understanding of how three-dimensional leaf forms are established. We focus on
how genes, phytohormones, and mechanical properties modulate leaf development,
and discuss these factors in the context of leaf initiation, polarity
establishment and maintenance, leaf flattening, and intercalary growth.
PMID- 29960100
TI - Adaptive homeostasis and the free radical theory of ageing.
AB - The Free Radical Theory of Ageing, was first proposed by Denham Harman in the mid
1950's, based largely on work conducted by Rebeca Gerschman and Daniel Gilbert.
At its core, the Free Radical Theory of Ageing posits that free radical and
related oxidants, from the environment and internal metabolism, cause damage to
cellular constituents that, over time, result in an accumulation of structural
and functional problems. Several variations on the original concept have been
advanced over the past six decades, including the suggestion of a central role
for mitochondria-derived reactive species, and the proposal of an age-related
decline in the effectiveness of protein, lipid, and DNA repair systems. Such
innovations have helped the Free Radical Theory of Aging to achieve widespread
popularity. Nevertheless, an ever-growing number of apparent 'exceptions' to the
Theory have seriously undermined its acceptance. In part, we suggest, this has
resulted from a rather simplistic experimental approach of knocking-out, knocking
down, knocking-in, or overexpressing antioxidant-related genes to determine
effects on lifespan. In some cases such experiments have yielded results that
appear to support the Free Radical Theory of Aging, but there are just as many
published papers that appear to contradict the Theory. We suggest that free
radicals and related oxidants are but one subset of stressors with which all life
forms must cope over their lifespans. Adaptive Homeostasis is the mechanism by
which organisms dynamically expand or contract the homeostatic range of stress
defense and repair systems, employing a veritable armory of signal transduction
pathways (such as the Keap1-Nrf2 system) to generate a complex profile of
inducible and enzymatic protection that best fits the particular need. Viewed as
a component of Adaptive Homeostasis, the Free Radical Theory of Aging appears
both viable and robust.
PMID- 29960107
TI - Four IVa bHLH Transcription Factors Are Novel Interactors of FIT and Mediate JA
Inhibition of Iron Uptake in Arabidopsis.
AB - Plants have evolved sophisticated genetic networks to regulate iron (Fe)
homeostasis for their survival. Several classes of plant hormones including
jasmonic acid (JA) have been shown to be involved in regulating the expression of
iron uptake and/or deficiency-responsive genes in plants. However, the molecular
mechanisms by which JA regulates iron uptake remain unclear. In this study, we
found that JA negatively modulates iron uptake by downregulating the expression
of FIT (bHLH29), bHLH38, bHLH39, bHLH100, and bHLH101 and promoting the
degradation of FIT protein, a key regulator of iron uptake in Arabidopsis. We
further demonstrated that the subgroup IVa bHLH proteins, bHLH18, bHLH19, bHLH20,
and bHLH25, are novel interactors of FIT, which promote JA-induced FIT protein
degradation. These four IVa bHLHs function redundantly to antagonize the activity
of the Ib bHLHs (such as bHLH38) in regulating FIT protein stability under iron
deficiency. The four IVa bHLH genes are primarily expressed in roots, and are
inducible by JA treatment. Moreover, we found that MYC2 and JAR1, two critical
components of the JA signaling pathway, play critical roles in mediating JA
suppression of the expression of FIT and Ib bHLH genes, whereas they
differentially modulate the expression of bHLH18, bHLH19, bHLH20, and bHLH25 to
regulate FIT accumulation under iron deficiency. Taken together, these results
indicate that by transcriptionally regulating the expression of different sets of
bHLH genes JA signaling promotes FIT degradation, resulting in reduced expression
of iron-uptake genes, IRT1 and FRO2, and increased sensitivity to iron
deficiency. Our data suggest that there is a multilayered inhibition of iron
deficiency response in the presence JA in Arabidopsis.
PMID- 29960108
TI - Quantitative Trait Loci Analysis Identifies a Prominent Gene Involved in the
Production of Fatty Acid-Derived Flavor Volatiles in Tomato.
AB - To gain insight into the genetic regulation of lipid metabolism in tomato, we
conducted metabolic trait loci (mQTL) analysis following the lipidomic profiling
of fruit pericarp and leaf tissue of the Solanum pennellii introgression lines
(IL). To enhance mapping resolution for selected fruit-specific mQTL, we profiled
the lipids in a subset of independently derived S. pennellii backcross inbred
lines, as well as in a near-isogenic sub-IL population. We identified a putative
lecithin:cholesterol acyltransferase that controls the levels of several lipids,
and two members of the class III lipase family, LIP1 and LIP2, that were
associated with decreased levels of diacylglycerols (DAGs) and triacylglycerols
(TAGs). Lipases of this class cleave fatty acids from the glycerol backbone of
acylglycerols. The released fatty acids serve as precursors of flavor volatiles.
We show that LIP1 expression correlates with fatty acid-derived volatile levels.
We further confirm the function of LIP1 in TAG and DAG breakdown and volatile
synthesis using transgenic plants. Taken together, our study extensively
characterized the genetic architecture of lipophilic compounds in tomato and
demonstrated at molecular level that release of free fatty acids from the
glycerol backbone can have a major impact on downstream volatile synthesis.
PMID- 29960109
TI - Prevalence of anatomic variations of the atlas vertebra.
AB - BACKGROUND CONTEXT: The retrotransverse foramen (RTF), arcuate foramen (AF),
unclosed transverse foramen (UTF) and posterior atlas arch defects (PAAD) are
anatomic variations of the atlas vertebra that surgeons must be aware of before
spine surgery is performed. PURPOSE: To analyze the prevalence of the AF, RTF,
UTF, and PAAD. STUDY DESIGN: Ex-vivo anatomical study. PATIENT SAMPLE: Two
hundred eighteen atlas vertebrae obtained from 100 Caucasian subjects and 118 sub
Saharan African subjects (48 Sotho subjects, 35 Xhosa subjects and 35 Zulu
subjects). METHODS: We studied 218 atlas vertebrae from skeletons of the Raymond
A. Dart Collection in order to analyze the prevalence of AF, RTF, UTF, and PAAD
in both Caucasian and sub-Saharan African subjects. OUTCOME MEASURES: Not
applicable. RESULTS: Sixty-nine (31.2%) atlases presented anatomical variants: 64
(29.3%) presented one anatomical variant, 4 (1.8%) presented two, and 1 (0.5%)
presented three. AF, RTF, UTF, Type A and Type E defects were present in 35
(16.1%), 17 (7.8%), 17 (7.8%), 5 (2.3%), and 1 (0.5%) vertebrae, respectively.
The vertebrae with two anatomical variants presented a bilateral UTF and a Type A
defect, a bilateral AF and a Type A defect, a right UTF and a left AF, and a
right UTF and a Type E defect. The vertebra with three anatomical variants
presented a bilateral RTF, a left UTF, and a left AF. No sex differences in
prevalence of the RTF (p=.775), AF (p=.605), UTF (p=.408) and Type A defects
(p=1.000) were found in the sub-Saharan African and Caucasian groups (RTF,
p=.306; AF, p=.346; UTF, p=.121; Type A defects, p=.561). Comparison between the
sub-Saharan African (all subjects) and the Caucasian group revealed no
differences in the UTF (p=.105), AF (p=.144), RTF (p=.542) and Type A defects
(p=.521) prevalence. Also, no differences in the prevalence of the UTF (p=.515),
AF (p=.278), and RTF (p=.857) between Zulu, Xhosa and Sotho subjects were found.
Neither were found sex differences in the prevalence of UTF, RTF and AF in Zulu
(p=.805, p=.234, p=.129), Xhosa (p=.269, p=.181, p=.309), and Sotho subjects
(p=.062, p=.590, p=.106). CONCLUSIONS: The present study has revealed no sex
differences in the prevalence of AF, UTF, RTF or PAAD in both Caucasian and sub
Saharan African subjects. This research has also indicated no differences in the
prevalence of the UTF, AF and RTF between Zulu, Xhosa and Sotho subjects. In
addition, this study has revealed no differences in the Type A, UTF, AF, and RTF
prevalence between the sub-Saharan African (all subjects) and the Caucasian
subjects. These variations may be known by surgeons before spine surgery for
better planning.
PMID- 29960110
TI - Electromyography stimulation compared with intraoperative O-arm imaging for
evaluating pedicle screw breaches in lumbar spine surgery: a prospective analysis
of 1006 screws in 164 patients.
AB - BACKGROUND CONTEXT: Lumbar pedicle screw placement can be technically
challenging. Malpositioned screws occur in up to 15% of patients and could result
in radiculopathy or instrumentation failure. PURPOSE: To compare intraoperative
electromyography (EMG) and image guidance using an O-arm for identifying pedicle
breach during elective lumbar fusion. STUDY DESIGN: Prospective observational
study. PATIENT SAMPLE: All adult patients undergoing elective lumbar spinal
fusion operations for degenerative spine disorders (including adjacent segment
degeneration, degenerative scoliosis, and symptomatic spondylosis and
spondylolisthesis) at a single institution from July 1, 2014, to December 1,
2015, were prospectively tracked. OUTCOME MEASURES: Pedicle breach. METHODS:
Pedicle screws from L2-S1 were placed using C-arm assisted freehand technique.
All screws were stimulated with EMG and evaluated using the O-arm intraoperative
imaging system. Electromyography data were compared with intraoperative images to
assess the accuracy of identifying pedicle breaches. No funding was received for
this work. RESULTS: One thousand six lumbar pedicles screws were placed from L2
to S1 in 164 consecutive cases. The mean patient age was 59.2 years. Thirty-five
breaches (15 lateral and 20 medial) were visualized with O-arm imaging and
confirmed by palpation (3.5% of screws placed). Of the breaches, 14 screws
stimulated below the 12-mA threshold, nine screws stimulated between 12 and 20
mA, and 12 screws did not generate an EMG response. Forty screws stimulated below
a 12-mA threshold but showed no breach on imaging. Using the 12-mA threshold, the
sensitivity of EMG was 40%, specificity was 96%, positive predictive value was
26%, and negative predictive value was 98%. All 35 breached screws were corrected
during surgery. There were no postoperative symptoms caused by breached screws
and no patients required reoperation. CONCLUSIONS: Our findings indicate that EMG
may not be a highly reliable tool in determining an anatomical breach during
placement of lumbar pedicle screws. O-arm may be better for detecting either
medial or lateral breaches than EMG stimulation if there are concerns about screw
placement or for confirmation of placement before leaving the operating room.
PMID- 29960111
TI - The association between pro-inflammatory biomarkers and nonspecific low back
pain: a systematic review.
AB - BACKGROUND CONTEXT: About 85% of the patients with low back pain seeking medical
care have nonspecific low back pain (NsLBP), implying that no definitive cause
can be identified. Nonspecific low back pain is defined as low back pain and
disability which cannot be linked to an underlying pathology, such as cancer,
spinal osteomyelitis, fracture, spinal stenosis, cauda equine, ankylosing
spondylitis, and visceral-referred pain. Many pain conditions are linked with
elevated serum levels of pro-inflammatory biomarkers. Outcomes of interest are
NsLBP and the level of pro-inflammatory biomarkers. PURPOSE: To unravel the
etiology and get better insight in the prognosis of NsLBP, the aim of this study
was to assess the association between pro-inflammatory biomarkers and the
presence and severity of NsLBP. STUDY DESIGN: A systematic literature search was
made in Embase, Medline, Cinahl, Webof-science, and Google scholar up to January
19th 2017. METHODS: Included were cross-sectional and cohort studies reporting on
patients aged over 18 years with NsLBP, in which one or more pro-inflammatory
biomarkers were measured in blood plasma. The methodological quality of the
included studies was assessed using the Newcastle Ottawa Scale. A best-evidence
synthesis was used to summarize the results from the individual studies, meaning
that the included studies were ranked according to the consistency of the
findings and according to their methodological quality score using the Newcastle
Ottawa Scale. RESULTS: Included were 10 studies which assessed four different pro
inflammatory biomarkers. For the association between the presence of NsLBP and C
reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF)
alpha limited, conflicting and moderate evidence, respectively, was found. For
the association between the severity of NsLBP and CRP and IL-6, moderate evidence
was found. For the association between the severity of NsLBP and TNF-alpha and
RANTES Regulated on Activation, Normal T Cell Expressed and Secreted conflicting
and limited evidence, respectively, was found. CONCLUSIONS: This study found
moderate evidence for (i) a positive association between the pro-inflammatory
biomarkers CRP and IL-6 and the severity of NsLBP, and (ii) a positive
association between TNF-alpha and the presence of NsLBP. Conflicting and limited
evidence was found for the association between TNF-alpha and Regulated on
Activation, Normal T Cell Expressed and Secreted and severity of NsLBP,
respectively.
PMID- 29960112
TI - Prognostic factors associated with best outcomes (minimal symptom state)
following fusion for lumbar degenerative conditions.
AB - BACKGROUND CONTEXT: Previous studies suggest that a postoperative symptom state
with Oswestry Disability Index (ODI)<=20 and pain Numeric Rating Scales (NRS)<=2
following surgery for lumbar degenerative conditions are reasonable thresholds
for best outcomes in which patients will be unlikely to seek additional medical
care or require additional health-care resources. PURPOSE: To identify prognostic
factors that predict a "best outcome," defined as postoperative ODI<=20 and pain
NRS<=2 following fusion for lumbar degenerative conditions. STUDY DESIGN:
Longitudinal observational cohort. PATIENT SAMPLE: A total of 396 patients from a
single site enrolled in the Quality Outcomes Database who underwent fusion for
lumbar degenerative conditions. OUTCOME MEASURES: Oswestry Disability Index, Back
and Leg Pain NRS (0-10). METHODS: Collected and analyzed variables included age,
sex, body mass index, American Society of Anesthesia grade, number of surgical
levels, surgical time, preoperative ODI, preoperative back pain, preoperative leg
pain, workmen compensation status, surgical approach, smoking status, and
principal diagnosis. RESULTS: A total of 74 patients (19%) reported a minimal
symptom state at 1-year postoperative (ODI<=20, back pain NRS<=2, and leg pain
NRS<=2) and were included in the best outcomes group. Patients in the best
outcomes group were older (62vs. 57years, p=.001), had lower preoperative ODI
(43vs. 56, p=.000), lower preoperative back pain (6.5vs. 7.5, p=.000). They had
fewer surgical levels (1.25vs. 1.47, p=.005) and shorter operative times [OR]
times (208vs. 241 minutes, p=.002). They were more likely to have a preoperative
diagnosis of spondylolisthesis or disc herniation and less likely to have a
diagnosis of adjacent segment disease or mechanical disc collapse (p=.001).
Stepwise forward regression analysis revealed diagnosis (p=.023, OR=0.75), age
(p=.000, OR=1.04), baseline ODI (p=.000, OR=0.96), and number of levels (p=.019,
OR=0.53) as predictive variables. CONCLUSION: Achieving a minimal symptom state,
defined here as a postoperative ODI<=20 and pain NRS<=2, following fusion for
lumbar degenerative conditions is more likely in an older patient with a lower
baseline ODI undergoing a single level lumbar fusion for spondylolisthesis.
PMID- 29960113
TI - The olive constituent oleuropein, as a PPARalpha agonist, markedly reduces serum
triglycerides.
AB - Oleuropein (OLE), a main constituent of olive, exhibits antioxidant and
hypolipidemic effects, while it reduces the infarct size in chow- and cholesterol
fed rabbits. Peroxisome proliferator-activated receptor alpha (PPARalpha) has
essential roles in the control of lipid metabolism and energy homeostasis. This
study focused on the mechanisms underlying the hypolipidemic activity of OLE and,
specifically, on the role of PPARalpha activation in the OLE-induced effect.
Theoretical approach using Molecular Docking Simulations and luciferase reporter
gene assay indicated that OLE is a ligand of PPARalpha. The effect of OLE (100
mg/kg, p.o., per day, *6 weeks) on serum triglyceride (TG) and cholesterol levels
was also assessed in adult male wild-type and Ppara-null mice. Molecular Docking
Simulations, Luciferase reporter gene assay and gene expression analysis
indicated that OLE is a PPARalpha agonist that up-regulates several PPARalpha
target genes in the liver. This effect was associated with a significant
reduction of serum TG and cholesterol levels. In contrast, OLE had no effect in
Ppara-null mice, indicating a direct involvement of PPARalpha in the OLE-induced
serum TG and cholesterol reduction. Activation of hormone-sensitive lipase in the
white adipose tissue (WAT) and the liver of wild-type mice and up-regulation of
several hepatic factors involved in TG uptake, transport, metabolism and
clearance may also contribute in the OLE-induced TG reduction. In summary, OLE
has a beneficial effect on TG homeostasis via PPARalpha activation. OLE also
activates the hormone sensitive lipase in the WAT and liver and up-regulates
several hepatic genes with essential roles in TG homeostasis.
PMID- 29960114
TI - Interaction between leucine and palmitate catabolism in 3T3-L1 adipocytes and
primary adipocytes from control and obese rats.
AB - Metabolic profiling studies have highlighted increases in the plasma free fatty
acid (FFA) and branched-chain amino acid (BCAA) concentrations, which are
hallmarks of the obese and insulin-resistant phenotype. However, little is known
about how the increase of the BCAA concentration modifies the metabolic fate of
FFA, and vice versa, in adipocytes. Therefore, we incubated differentiated 3T3-L1
adipocytes or primary adipocytes from rats fed a control or a high-fat diet with:
(1) 0, 250, 500 and 1000 MUM of leucine and determined the oxidation and
incorporation of [1-14C]-palmitate into lipids or proteins or (2) 0, 250, 500 or
1000 MUM of palmitate and evaluated the oxidation and incorporation of [U-14C]
leucine into lipids or proteins. Leucine decreased palmitate oxidation and
increased its incorporation into the lipid fraction in adipocytes; the latter was
reduced in adipocytes from obese rats. However, palmitate increased leucine
oxidation in adipocytes as well as reduced leucine incorporation into the protein
and lipid fractions in adipocytes from obese rats. These results demonstrate that
leucine modifies the metabolic fate of palmitate, and vice versa, in adipocytes
and that the metabolic interaction between leucine and palmitate catabolism is
altered in adipocytes from obese rats.
PMID- 29960115
TI - Chronic palmitic acid-induced lipotoxicity correlates with defective trafficking
of ATP sensitive potassium channels in pancreatic beta cells.
AB - Lipotoxicity is associated with a high level of fatty acid accumulation in
pancreatic beta-cells. An overload of free fatty acids contributes to pancreatic
beta-cell apoptosis and dysfunction. Insulin secretion involves sequential ionic
events upon glucose stimulation. ATP sensitive potassium (KATP) channels serve as
glucose sensors and effectively initiate glucose-stimulated insulin secretion.
This study investigated the effects of lipotoxicity on the trafficking of KATP
channels in pancreatic beta cells using chronic palmitic acid -injected mice and
treated insulinoma cells. The chronic palmitic acid -injected mice displayed type
II diabetic characteristics. The pancreatic sections of these mice exhibited a
decrease in the expression of KATP channels. We then tested the time and dose
effects of palmitic acid on the cell viability of INS-1 cells. We observed a
significant decrease in the surface expression of KATP channels after 72 h of
treatment with 0.4 mM palmitic acid. In addition, this treatment induced
pancreatic beta-cell apoptosis by increasing cleaved caspase 3 protein level. Our
results demonstrated cotreatment with glibenclamide, the sulfonylurea compounds
for type II diabetes mellitus, in palmitic acid -treated cells reduces cell death
and recovers the glucose stimulated insulin secretion through increasing the
surface expression of KATP channels. Importantly, glibenclamide also improved
glucose tolerance, triglyceride concentration, and insulin sensitivity in the
palmitic acid-injected mice. In conclusion, an increase in the surface expression
of KATP channels restores insulin secretion, reduces pancreatic beta-cell's
apoptosis, highlighting correct trafficking of KATP channels is important in
survival of beta-cells during lipotoxicity.
PMID- 29960116
TI - Association of serum zinc with markers of liver injury in very heavy drinking
alcohol-dependent patients.
AB - Zinc deficiency is a frequent complication of alcohol abuse for multiple reasons
including poor intake, increased excretion, internal redistribution and altered
transporters. Zinc deficiency has been postulated to play a role in the
development/progression of alcoholic liver disease (ALD). This study aimed to
relate serum zinc levels with alcohol intake, serum albumin concentration and
markers of inflammation and liver injury. One hundred and eight male and female
very heavy drinking (>=10 drinks/day) individuals without clinical evidence of
ALD were grouped by serum zinc concentration: normal-zinc group (zinc level>=71
MUg/dl) included 67 patients, and low-zinc group (zinc level<71 MUg/dl) included
41 patients. Data were collected on demographics, drinking history in last 90
days (heavy drinking days, HDD90 and total drinks, TD90), lifetime drinking
history (LTDH) and clinical/ laboratory assessments. Our data show that in a very
well-characterized, chronically heavy-drinking population without clinical
evidence of liver disease, about 40% of subjects had low serum zinc levels.
Frequency of heavy drinking days (HDD90) was significantly higher in the low-zinc
group. Total drinks in past 90 days, LTDH and HDD90 showed significant
associations with low zinc levels. The group with the low serum zinc had a higher
aspartate aminotransferase/alanine aminotransferase ratio (good marker of
alcoholic liver disease). Those in the low-zinc group had the lower albumin
levels, a marker of hepatic synthetic function, and the highest C-reactive
protein level, a biomarker of inflammation.
PMID- 29960117
TI - Copper supplementation reverses dietary iron overload-induced pathologies in
mice.
AB - Dietary iron overload in rodents impairs growth and causes cardiac hypertrophy,
serum and tissue copper depletion, depression of serum ceruloplasmin (Cp)
activity and anemia. Notably, increasing dietary copper content to ~25-fold above
requirements prevents the development of these physiological perturbations.
Whether copper supplementation can reverse these high-iron-related abnormalities
has, however, not been established. The current investigation was thus undertaken
to test the hypothesis that supplemental copper will mitigate negative outcomes
associated with dietary iron loading. Weanling mice were thus fed AIN-93G-based
diets with high (>100-fold in excess) or adequate (~80 ppm) iron content. To
establish the optimal experimental conditions, we first defined the time course
of iron loading, and assessed the impact of supplemental copper (provided in
drinking water) on the development of high-iron-related pathologies. Copper
supplementation (20 mg/L) for the last 3 weeks of a 7-week high-iron feeding
period reversed the anemia, normalized serum copper levels and Cp activity, and
restored tissue copper concentrations. Growth rates, cardiac copper
concentrations and heart size, however, were only partially normalized by copper
supplementation. Furthermore, high dietary iron intake reduced intestinal 64Cu
absorption (~60%) from a transport solution provided to mice by oral,
intragastric gavage. Copper supplementation of iron-loaded mice enhanced
intestinal 64Cu transport, thus allowing sufficient assimilation of dietary
copper to correct many of the noted high-iron-related physiological
perturbations. We therefore conclude that high- iron intake increases the
requirement for dietary copper (to overcome the inhibition of intestinal copper
absorption).
PMID- 29960118
TI - Potential of electrical impedance spectroscopy to differentiate between healthy
and osteopenic bone.
AB - : Osteoporosis involves loss of structural stability of bone due to an increase
in bone porosity. Dual energy X-ray absorptometry is used to evaluate bone in
terms of quantity. However, it does not give an evaluation of the patient's bone
quality. For this, present study has been carried out to assess the structural
deterioration of bone using electrical impedance spectroscopy. METHODS:
Electrical Impedance Spectroscopy has been applied to evaluate the structural and
compositional changes of cortical bone in the frequency range of 50 Hz to 5 MHz
for the ovariectomized rat model. Initially, bone resorption in the
ovariectomized group has been confirmed by estimating tartaric resistant acid
phosphatase levels; morphometric parameters; bone matrix components,
hydroxyapatite crystallite size and bone micro architecture. The mid diaphyseal
regions from the femora and tibiae of sixty days post ovariectomy and control
rats were used for the measurement of dielectric parameters. A dispersion model
based analysis has been developed by a complex least square fitting of the
dielectric data. FINDINGS: Increased tartaric resistant acid phosphatase levels,
altered bone matrix components, hydroxyapatite crystallite size and disturbed
microarchitecture in the ovariectomized group give us the confirmation of
increased bone resorption following estrogen deficiency. These changes were shown
to be reflected by single dispersion model based fitted parameters which shows
the considerable change in all the parameters of ovariectomized group compared to
the control. INTERPRETATION: It has been demonstrated that the parameters of the
dispersion model can reflect the bone structural and compositional changes.
PMID- 29960119
TI - Assessment the ecotoxicity and inhibition of imidazolium ionic liquids by
respiration inhibition assays.
AB - The ecotoxicity and inhibition of 12 imidazolium ionic liquids (ILs) with alkyl
chain from C4 to C10 and chloride (Cl-), tetrafluoroborate (BF4-) and
bis(trifluoromethanesulfonyl)imide (NTf2-) anions have been studied by means of
respiration inhibition assays using activated sludge collected from a wastewater
treatment plant. This test represents an alternative easy, economic and quick way
to evaluate the true impact of ILs on activated sludge-based wastewater
treatment. For comparison purposes, the EC50 values were also determined by the
Microtox test (Vibrio fischeri). It was observed that this widely used microbial
test overestimates the effect of the ILs on biological wastewater treatment
facilities, especially in the case of ILs with lower ecotoxicity. The results of
the biological tests showed that the alkyl chain length plays a crucial role in
the ecotoxicity of ILs. A significant increase of the toxicity with the length of
the n-alkyl chain was found. Regarding to the impact of the anion, the
ecotoxicity measured by respiration inhibition assays follows the order NTf2- >
Cl- > BF4-, being the anion effect higher as decreasing the length of cation
alkyl chain. According to the hazard substances ranking for aquatic organisms
(Passino and Smith, 1987), imidazolium ILs with C4 alkyl chain can be classified
as "practically harmless" compounds whereas those with alkyl chains C8 or C10
correspond to "highly toxic" species.
PMID- 29960120
TI - Screening ornamental plants to identify potential Cd hyperaccumulators for
bioremediation.
AB - To identify possible cadmium (Cd) accumulators or hyperaccumulators among
ornamental plants, a pot experiment involving increasing Cd concentration (0, 5,
15, 30, 60, and 100 mg kg-1) was conducted among seven species. The principal
objective was to screen for ornamental plants with an exceptional ability to
accumulate and translocate Cd ions as well as sufficient biomass for harvesting.
Regarding shoot biomass, root biomass, plant height and tolerance index (TI),
Malva rotundifolia showed high tolerance to Cd and Malva crispa, Sida
rhombifolia, Celosia argentea and Celosia cristata medium tolerance; Althaea
rosea and Abutilon theophrasti were more sensitive to Cd than the other plants. A
hormetic response was induced by Cd in M. crispa, C. argentea, C. cristata and M.
rotundifolia. Based on its capacity for Cd accumulation, bioaccumulation
coefficients (BCFs) and translocation factors (TFs), M. rotundifolia was selected
from candidate plants after 60 days of exposure to Cd-contaminated soil and found
to have accumulated more than 200 mg kg-1 Cd in its roots and 900 mg kg-1 in its
shoots. Moreover, M. rotundifolia BCFs and TFs were higher than 1.0, with the
former ranging from 1.41 to 3.31 and the latter from 1.03 to 7.37. Taken
together, these results indicate that M. rotundifolia can be classified as a
model hyperaccumulator.
PMID- 29960121
TI - NiO/Ni/TiO2 nanocables with Schottky/p-n heterojunctions and the improved
photocatalytic performance in water splitting under visible light.
AB - Construction of Schottky junction or p-n heterojunction is admitted as an
effective way for improving the separation of photo-induced carriers through its
built-in electric field. In this work, fabrication of cooperative Schottky and p
n (SPN) heterojunction has been realized by intercalating metal Ni into a
NiO/TiO2p-n junction, forming a NiO/Ni/TiO2 Sandwich-like heterojunction. The
special heterostructure was confirmed by X-ray powder diffraction (XRD), X-ray
photoelectron spectroscopy (XPS), scanning electron microscopy (SEM),
transmission electron microscopy (TEM) and the high-resolution transmission
electron microscopic (HRTEM), Brunauer Emmett Teller (BET). After a serial of
contrast experiments with solo Schottky or p-n junction, it was found that the
electron-hole separation in this NiO/Ni/TiO2 SPN heterojunction was enhanced
through charge transfer channel, and it was also in accordance with their related
optical and photoelectrical properties characterizations, such as
photoluminescence (PL) spectrum and UV-Vis diffused reflectance spectra. In the
following photocatalytic water splitting process under visible light, the
hydrogen generation rate of NiO/Ni/TiO2 reached up to 4653 MUmol h-1 g-1, which
was 10.2, 6.7 and 2.3 times of those of TiO2 (457 MUmol h-1 g-1), Ni/TiO2 (691
MUmol h-1 g-1) with a Schottky junction and NiO/TiO2 (2059 MUmol h-1 g-1) with a
p-n junction, respectively. This SPN heterojunction with excellent photo-induced
electron-hole separation ability opens a new window to exploring photocatalyst
for water splitting.
PMID- 29960122
TI - Insight in to the degradation of bisphenol A by doped ZnO@ZnHCF nanocubes: High
photocatalytic performance.
AB - Bisphenol-A (BPA) is suspected of been endocrine-disrupter and carcinogen. Hence,
removal of extensively used BPA by low-cost and efficient coupled-nanomaterials
is viewed as vital to environmental protection. Herein, nanocomposite of ZnO
doped with zinc-hexacyanoferrate (ZnO@ZnHCF) was employed for photodegradation of
BPA. Green synthesized nanocomposite consisted of ZnO wrapped ZnHCF distorted
nanocubes piled together. Under daylight, prompt early exponential decline in
concentration over time revealed elevated photo-activity of nanocomposite.
Improvement in surface-area (113.491 m2g-1) and band-gap (2.2 eV) of catalyst was
resulted from synergism of semiconducting and intercalative feature of ZnO and
ZnHCF. At optimum catalyst-dose (25 mg) and neutral pH, photodegradation of BPA
(97% of 2 mgL-1) followed first-order-kinetics involving initial Langmuir
adsorption isotherms (R2 >= 0.996; p <= 0.05). Nanocomposites were more effective
for greater adsorption of BPA (Xm = 18.0 mg g-1) than the ZnHCF (10.8 mg g-1) and
ZnO (3.9 mg g-1). Moreover, doped ZnO@ZnHCF reduced the half-life of BPA upto 2.8
h than that with bared ZnHCF (8 h) and ZnO (17.4 h). GC-MS revealed presence of
smaller and safer byproducts clearly supported electron excitement from wrapped
nanocomposite followed by oxidation of BPA with countless OH. Degradation
pathways were constructed to track-ways leading to mineralization. Overall, due
to greater surface-activity, reusability upto ten-cycles and charge separation (e
+h+ pairs) led to promotion of huge free radicals, ZnO@ZnHCF might be supposed a
promising photocatalyst.
PMID- 29960123
TI - Biodegradable nanocomposite of glycerol citrate polyester and ultralong
hydroxyapatite nanowires with improved mechanical properties and low acidity.
AB - Glycerol citrate polyester based on the condensation of glycerol and citric acid
has a great potential in biomedical applications owing to biocompatible monomers
and biodegradation properties. However, the applications of glycerol citrate
polyester are impaired by its poor mechanical properties and high acidity caused
by citric acid produced in the degradation process. In this work, a new kind of
nanocomposite has been developed using ultralong hydroxyapatite (HAP) nanowires
as the "skeleton", and strongly bound glycerol citrate polyester as the "muscle".
The ultralong HAP nanowires interweave with each other to form a three
dimensional nanoporous network, and glycerol citrate polyester is homogeneously
distributed in the nanoporous network. Owing to the reinforcement of ultralong
HAP nanowires, the mechanical properties of the as-prepared nanocomposite are
significantly improved compared with the pure glycerol citrate polyester, and the
tensile strength even reaches to the level of human cortical bones. Furthermore,
the acidity of the aqueous solution after degradation is neutralized by the
reaction between citric acid and ultralong HAP nanowires, and the pH value can be
stabilized. The as-prepared nanocomposite can solve some problems of the pure
glycerol citrate polyester, and shows promising applications in the biomedical
field.
PMID- 29960124
TI - A systematic review and meta-analysis of clinicopathologic factors linked to
oncologic outcomes for renal cell carcinoma with tumor thrombus treated by
radical nephrectomy with thrombectomy.
AB - BACKGROUND: There remain discrepancies over the factors that influence oncologic
outcomes after radical nephrectomy with thrombectomy (RNTE). To assess
significant predictors of oncologic outcomes after RNTE from a systematic review
and meta-analysis. METHODS: A comprehensive search of PubMed, Embase, Cochrane
Library and Web of Science was performed to identify eligible studies. The
endpoints included cancer-specific survival (CSS), overall survival (OS), and
recurrence-free survival (RFS). A formal meta-analysis was performed for studies
containing non-metastatic and metastatic tumors. Additionally, a sensitivity
analysis including the subgroup of studies containing non-metastatic tumors only
was conducted. Cumulative analyses of hazard ratios (HRs) and their corresponding
95% confidence intervals (CIs) were conducted. RESULTS: Overall, 35 retrospective
studies of low to moderate risk of bias including 11,929 patients were included.
The results indicated that large tumor size, high Fuhrman grade, tumor necrosis,
positive lymph node, and metastasis at surgery were adverse significant
predictors for both CSS and OS. Also, IVC tumor thrombus, sarcomatoid
differentiation, perinephretic fat invasion, and adrenal gland invasion were
associated with poor CSS. In the subset of non-metastatic patients, the
significant predictors were clinical symptom, thrombus level, Fuhrman grade and
adrenal gland invasion for CSS; thrombus consistency, Fuhrman grade and tumor
necrosis for OS; tumor size, Fuhrman grade and perinephretic fat invasion for
RFS. CONCLUSIONS: A meta-analysis of available data identified significant
prognostic factors of CSS, OS and RFS that should be systematically evaluated to
propose a risk-adapted approach to postoperative patient counseling, risk
stratification, and therapy selection.
PMID- 29960125
TI - Autobiographical memory retrieval and appraisal in social anxiety disorder.
AB - Individuals with social anxiety disorder (SADs; n = 41) and healthy controls
(HCs; n = 40) were administered the Waterloo Images and Memories Interview, in
which they described mental images that they tend to experience in both anxiety
provoking and non-anxiety-provoking social situations. Participants then
recalled, in as much detail as possible, specific autobiographical memories of
salient aversive and non-aversive social experiences that they believed led to
the formation of these images. Audio-recorded memory narratives were transcribed
and coded based on the procedure of the Autobiographical Interview, which
provides a precise measure of the degree of episodic detail contained within each
memory. Participants also rated the subjective properties of their recalled
memories. Results revealed that participants across the two groups retrieved
equivalent rates of both aversive and non-aversive social memories. However, SAD
participants' memories of aversive events contained significantly more episodic
detail than those of HCs, suggesting that they may be more highly accessible.
Moreover, participants with SAD appraised their memories of aversive experiences
as more distressing and intrusive than HCs, and perceived them as having a
significantly greater influence on their self-perception. In contrast, no group
differences were observed for memories of non-aversive events. Findings have the
potential to shed new light on autobiographical memory in SAD, with implications
for psychotherapeutic intervention.
PMID- 29960126
TI - Mechanisms, genes and treatment: Experimental fear conditioning, the serotonin
transporter gene, and the outcome of a highly standardized exposure-based fear
treatment.
AB - There is considerable interindividual variation in response to
psychotherapeutical intervention. In order to realize the long-term goal of
personalised treatment approaches, it is important to identify behavioural and
biological moderators and mediators of treatment responses. Here, we tested the
predictive value of experimental fear extinction efficacy as well as the role of
genetic variation of the serotonin transporter gene for the outcome of a fear
exposure treatment. A discriminative fear conditioning paradigm was conducted in
159 adults highly fearful of spiders, dental surgeries or blood, injuries and
injections. Participants were genotyped for the long (L) and short (S) allelic
variant of the serotonin transporter gene linked polymorphic region (5HTTLPR) and
treated with a highly standardized exposure-based one-session treatment.
Participants' subjective fear was assessed during experimental fear conditioning
and extinction. Furthermore, subjective phobic fear was assessed at pre-, post
and at 7 months follow-up treatment assessment. A threat-biased contingency
learning pattern characterized by exaggerated fear responses to the CS- was
associated with larger initial subjective fear reduction immediately following
the large-group treatment, p = .03. There were no learning pattern-associated
differences in subjective fear at 7-month follow-up. The odds of homozygous s
allele carriers to display a threat-biased contingency learning pattern were 3.85
times larger compared to l-allele carriers, p = .01. Fear-recovery in homozygous
S-allele carriers at follow-up assessment, p = .01, emerged regardless of the
experimental fear acquisition pattern. Our results suggest the homozygous S
allele carriers are biologically biased towards ignoring safety signals in threat
related situations. Short-term, this response pattern might be positively related
to the outcome of exposure treatments, potentially due to increased responding to
safe context conditions or a stronger violation of threat expectancies. However,
alterations in inhibiting the response to cues formerly signalling threat
evidenced for S-allele carriers can have negative impact on exposure success.
PMID- 29960127
TI - The evolutionary history of human populations in Europe.
AB - I review the evolutionary history of human populations in Europe with an emphasis
on what has been learned in recent years through the study of ancient DNA. Human
populations in Europe ~430-39kya (archaic Europeans) included Neandertals and
their ancestors, who were genetically differentiated from other archaic Eurasians
(such as the Denisovans of Siberia), as well as modern humans. Modern humans
arrived to Europe by ~45kya, and are first genetically attested by ~39kya when
they were still mixing with Neandertals. The first Europeans who were
recognizably genetically related to modern ones appeared in the genetic record
shortly thereafter at ~37kya. At ~15kya a largely homogeneous set of hunter
gatherers became dominant in most of Europe, but with some admixture from
Siberian hunter-gatherers in the eastern part of the continent. These hunter
gatherers were joined by migrants from the Near East beginning at ~8-9kya:
Anatolian farmers settled most of mainland Europe, and migrants from the Caucasus
reached eastern Europe, forming steppe populations. After ~5kya there was
migration from the steppe into mainland Europe and vice versa. Present-day
Europeans (ignoring the long-distance migrations of the modern era) are largely
the product of this Bronze Age collision of steppe pastoralists with Neolithic
farmers.
PMID- 29960128
TI - The natural history of crouch gait in bilateral cerebral palsy: A systematic
review.
AB - AIM: To systematically review the natural history of crouch gait in bilateral
cerebral palsy (CP) in the absence of surgical intervention and to review any
relationship between clinical variables and progression of knee crouch. METHODS:
Relevant literature was identified by searching article databases (PubMed,
CINAHL, EMBASE, and Web of Science). Included studies reported on participants
with bilateral CP who had 3-dimensional gait analysis on at least two occasions
with no surgical interventions between analyses. RESULTS: Five papers (4
retrospective cohort studies; 1 case report) comprised the final selection.
Studies varied in follow-up times and participant numbers. Increased knee flexion
over time was reported in the four retrospective studies with two distinct
patterns of increasing knee flexion evident. Only the case-study reported
improved knee extension between assessments. Four studies demonstrated increased
hamstring tightness over time with the biggest increases related to longer follow
up time rather than increase in crouch. CONCLUSION AND IMPLICATIONS: The existing
literature suggests that the natural history of crouch gait is towards increasing
knee flexion over time. Future prospective studies of bigger groups are needed to
examine the relationship between increasing crouch and clinical variables.
PMID- 29960129
TI - SCoT: Swept coherence transfer for quantitative heteronuclear 2D NMR.
AB - Nuclear magnetic resonance (NMR) spectroscopy is frequently applied in
quantitative chemical analysis (qNMR). It is easy to measure one-dimensional (1D)
NMR spectra in a quantitative regime (with appropriately long relaxation delays
and acquisition times); however, their applicability is limited in the case of
complex samples with severe peak overlap. Two-dimensional (2D) NMR solves the
overlap problem, but at the cost of biasing peak intensities and hence
quantitativeness. This is partly due to the uneven coherence transfer between
excited/detected 1H nuclei and the heteronuclei coupled to them (typically 13C).
In the traditional approach, the transfer occurs via the evolution of a spin
system state under the J-coupling Hamiltonian during a delay of a fixed length.
The delay length is set on the basis of the predicted average coupling constant
in the sample. This leads to disturbances for pairs of nuclei with coupling
constants deviating from this average. Here, we present a novel approach based on
non-standard processing of the data acquired in experiments, where the coherence
transfer delay is co-incremented with non-uniformly sampled evolution time. This
method allows us to obtain the optimal transfer for all resonances, which
improves quantitativeness. We demonstrate the concept for the coherence transfer
and multiplicity-edit delays in a heteronuclear single-quantum correlation
experiment (HSQC).
PMID- 29960130
TI - A study of MR signal reception from a model for a battery cell.
AB - Number of NMR/MRI studies on batteries is rapidly increasing in the past decade.
As the test batteries designed for the studies contain metal parts such as
electrodes and lead wires as well as other conductive parts (electrolyte), which
all present obstacles for good MR signal reception, understanding of the role of
battery design and of battery interactions with magnetic field is of a key
importance for a successful performance of the experiments. For the study, five
different samples mimicking a real battery cell were made. All the samples had
two parallel copper electrodes separated by a gel layer, however, they differed
in electrode thickness, gel conductivity and separation between the electrodes.
The samples were inserted in an MRI magnet in different orientations with respect
to magnetic fields B0 and B1 and scanned with the spin-echo and single point
imaging methods in 2D and 3D (spin-echo only). The performed experiments
confirmed that the main reason for poor MR signal reception from a test battery
are RF-induced eddy currents. These were found stronger with the sample with the
smaller distance between the electrodes. The effect of RF-induced eddy currents
was efficiently suppressed when the sample was oriented with the electrodes
parallel to the B1 field. However, in the orientation there were still
susceptibility effects that caused a signal voiding in a narrow region near the
electrodes. The susceptibility effects were found lower with the sample with thin
electrodes and the non-conductive gel. The results of the study can help
optimizing test battery and capacitor designs for NMR/MRI experiments.
PMID- 29960131
TI - The revised four-factor motivational thought frequency and state motivation
scales for alcohol control.
AB - INTRODUCTION: Elaborated Intrusion (EI) Theory holds that both functional and
dysfunctional motivational cognitions are characterized by their intensity,
cognitive availability and involvement of imagery, and can be assessed in terms
of their frequency and cross-sectional nature. Recently published data on the
Motivational Thought Frequency (MTF-A) and State Motivation (SM-A) scales for
alcohol control, which were based on EI theory, have shown acceptable fit for a
three-subscale structure (Intensity, Imagery, Availability). However, subsequent
analyses on the MTF's adaptation to diabetic regimen adherence suggested superior
fit from a four-factor model, splitting Imagery into Incentives and Self-Efficacy
Imagery. The current paper reanalyzed data on the MTF-A and SM-A, including an
additional item on each and using a more robust statistical approach. METHODS:
Participants (n = 504) reporting recent high-risk drinking or were currently
trying to control alcohol consumption volunteered to complete an online survey
that included the MTF-A, SM-A, Alcohol Use Disorders Identification Test and
Readiness to Change Questionnaire. Confirmatory factor analyses employed robust
maximum likelihood (MLR) with Yuan-Bentler chi2 adjustment, and presented
internal consistencies using omega. RESULTS: After omission of multivariate
outliers, SM-A data were available from 399 participants, and MTF-A data from
351. Better fit was found for the four-factor model on both measures, and high
internal consistencies were obtained for all subscales. Incentives Imagery and
Self-Efficacy Imagery were both associated with greater alcohol problems and
readiness to change. CONCLUSIONS: The four-factor structures are statistically
superior and more theoretically coherent, and allow a focused assessment of key
targets of motivational interventions.
PMID- 29960132
TI - Expanding the reach of alcohol and other drug services: Prevalence and correlates
of US adult engagement with online technology to address substance problems.
AB - Online technologies are well integrated into the day-to-day lives of individuals
with alcohol and other drug (i.e., substance use) problems. Interventions that
leverage online technologies have been shown to enhance outcomes for these
individuals. To date, however, little is known about how those with substance use
problems naturally engage with such platforms. In addition, the scientific
literatures on health behavior change facilitated by technology and harms driven
by technology engagement have developed largely independent of one another. In
this secondary analysis of the National Recovery Study (NRS), which provides a
geo-demographically representative sample of US adults who resolved a substance
use problem, we examined a) the weighted prevalence estimate of individuals who
engaged with online technologies to "cut down on substance use, abstain from
substances, or strengthen one's recovery" (i.e., recovery-related use of online
technology, or ROOT), b) clinical/recovery correlates of ROOT, controlling for
demographic covariates, and c) the unique association between ROOT and self
reported history of internet addiction. Results showed one in ten (11%) NRS
participants reported ROOT. Significant correlates included greater current
psychological distress, younger age of first substance use, as well as history of
anti-craving/anti-relapse medication, recovery support services, and drug court
participation. Odds of lifetime internet addiction were 4 times greater for those
with ROOT (vs. no ROOT). These data build on studies of technology-based
interventions, highlighting the reach of ROOT, and therefore, the potential for a
large, positive impact on substance-related harms in the US.
PMID- 29960133
TI - Suicide prevention activities in Bangladesh.
PMID- 29960134
TI - Selective mutism in a child with autism spectrum disorder: A case report and an
approach to the management in such difficult to treat scenario in children.
PMID- 29960135
TI - RNA-Seq analysis of differentially expressed genes in the grand jackknife clam
Solen grandis under aerial exposure.
AB - Aerial exposure tolerance has been long considered as an important trait for the
life survival under acute environmental stress. In this study, we utilized RNA
seq-based transcriptomic profiling to characterize the molecular responses of
grand jackknife clam in response to aerial exposure. This assembly yielded
190,856 unigenes with an average length of 1147 bp, a minimum length of 201 bp,
and a maximum length of 51,869 bp, with an N50 length of 1875 bp. After
differential expression analysis, a total of 1344 genes were captured
significantly differentially expressed, and were categorized into
antioxidant/oxidative stress response, immune alteration, and apoptosis. GO and
KEGG analyses revealed that signal transduction, immune response, cellular
component organization or biogenesis, and energy production processes were the
most highly enriched pathways among the genes that were differentially expressed
under aerial exposure stress. All these pathways could be assigned to the
following biological functions in the aerial exposure tolerant Solen grandis:
signaling, transporter activity, macromolecular complex, cellular component
organization or biogenesis, and molecular transducer activity. This study
highlighted candidate genes linked to stress response during aerial exposure and
provide a useful resource for further work on gills tissue or for selection of
aerial exposure tolerant phenotypes.
PMID- 29960136
TI - Speech rate adjustment of adults during conversation.
AB - PURPOSE: Speech rate convergence has been reported previously as a phenomenon in
which one's speech rate is influenced by his/her partner's speech rate. This
phenomenon has been demonstrated in artificial settings, and to some extent, in
mother-child interactions. The purpose of this study was to explore speech rate
adjustment in a quasi-natural adult-adult conversation. METHODS: An A-B-A-B
paradigm was used, in which ten adults conversed on a given topic with two
experimenters. Speech rates of both communication partners were measured.
RESULTS: Participants significantly reduced their speech rate, in response to the
experimenters' reduction in speech rate. However, the participants' reduction in
speech rate was significantly smaller than the experimenters' reduction in speech
rate. In addition, during the controlled slow speech rate, the participants'
speech rate correlated negatively with that of the experimenters'. CONCLUSION:
Results suggest that speech rate convergence is a non-linear phenomenon, and may
be affected by various linguistic as well as communicational factors. From a
clinical perspective, the results support the use of the modeling strategy in
speech therapy, as a means to facilitate a reduction in clients' speech rate.
PMID- 29960137
TI - Clinical experiences with ultrasound-guided supra-inguinal fascia iliaca block: A
new approach.
PMID- 29960138
TI - Persistent cortical blindness following total laparoscopic distal gastrectomy.
PMID- 29960139
TI - Patients with Binge Eating Disorder and Obesity have qualitatively different
interpersonal characteristics: Results from an Interpersonal Circumplex study.
AB - BACKGROUND: Patients with Binge Eating Disorder (BED) and obesity experience
distressing relationships, which could trigger negative affect and over-eating.
To date no studies compared the interpersonal profiles and prototypicality of
both groups using the Interpersonal Circumplex. METHOD: A sample of 177 patients
with BED (mean age: 41.0 +/- 12.5 years; 11.3% males), 321 obese non-BED adults
(mean age: 44.5 +/- 13.4 years; 28% males), and 108 normal weight adults (mean
age: 37.3 +/- 9.6 years; 52.77% males) completed the Inventory of Interpersonal
Problems (IIP-32), and scales of binge eating and psychological distress at one
time-point. RESULTS: Compared to normal weight and obese participants, those with
BED reported higher levels of interpersonal problems on all circumplex
dimensions, except for Vindictive, with small to medium effects. All groups had
highly prototypical profiles. Both obese and normal weight adults had very
similar interpersonal profiles characterized by predominant friendly-dominant
themes. On the contrary, those with BED had predominant friendly-submissive
themes. Patients with BED reported significantly higher levels of psychological
distress and binge eating severity, compared to the other two groups. Greater
Domineering, Cold, Socially Inhibited and Non-Assertive scale scores, and lower
Vindictive scale scores significantly predicted higher binge eating and
psychological distress, regardless of group membership. DISCUSSION: Findings lend
support to an interpersonal model of binge eating and to the presence of
qualitative differences between patients with obesity and BED. Finally, results
suggest some strategies for the clinical management of BED focused on non
assertion and problems with experiences and expression of anger.
PMID- 29960140
TI - Effect of ampicillin on adhesive properties of bacteria examined by atomic force
microscopy.
AB - Discovery of new antibacterial agents requires the development of novel
techniques for bacteria surface characterization after treatment with
antibiotics. In this study, we investigate the effect of ampicillin at MICs
levels on adhesive properties of Gram-positive and Gram-negative bacteria, using
atomic force microscopy (AFM). Our results revealed that the treatment leads to
changes of bacterial surface properties, especially cell surface roughness. A
nanomechanical alteration of the cells led to an increase of adhesive forces and
rupture lengths. Changes in adhesive properties are determined not only by the
modification of physicochemical cell properties but also by an increase in
roughness, leading to an increase of the contact area with a cantilever tip. We
discovered that the contribution of non-specific physicochemical interactions in
the bacteria attachment to a substrate is not negligible and was significantly
influenced by the presence of antibiotic. Ampicillin caused much greater change
in the adhesion properties of Bacillus subtilis than Escherichia coli due to the
mode of action of beta-lactam antibiotic. Adhesion measurements may by a new way
to investigate subtle changes of the bacterial surface properties caused by
antibiotic, especially those targeting the bacterial cell wall. In contrast to
nanoindentation assays, they provide information on adhesive properties of the
bacteria surface.
PMID- 29960141
TI - Dynamic spasticity determines hamstring length and knee flexion angle during gait
in children with spastic cerebral palsy.
AB - BACKGROUND: Previous researchers reported that popliteal angle did not correlate
well with knee angle during gait in individuals with spastic cerebral palsy (CP).
RESEARCH QUESTION: To determine if hamstring spasticity, as measured by Modified
Tardieu Scale (MTS) at rest, is associated with knee flexion angle at initial
contact and midstance during gait. METHODS: Thirty ambulatory children (mean age
8.7 +/- 2.4 years) diagnosed with spastic CP participated. The hamstrings'
spasticity was assessed in the supine position with the MTS, measuring R1 (muscle
reaction to passive fast stretch), R2 (passive range of motion), and R2-R1
(dynamic component of spasticity). We conducted 3-dimensional computerized gait
analysis and calculated semimembranosus muscle-tendon length and lengthening
velocity during gait using musculoskeletal modeling and inverse kinematic
analysis by OpenSim. Pearson correlation coefficients were calculated to estimate
the association of MTS with biomechanical parameters during gait. RESULTS: Knee
flexion angle at initial contact and maximal knee extension angle during stance
phase significantly positively correlated with both R1 and ?R2 - R1? of MTS, but
not with R2 angle. The length of semimembranosus at initial contact, end of
swing, and minimal length during stance phase were strongly negatively associated
with R1, rather than R2 or ?R2 - R1? angles. SIGNIFICANCE: The R1 angle of MTS
(muscle reaction to passive fast stretch) is more relevant correlate of knee
flexion angle during gait than the R2 (passive range of motion).
PMID- 29960142
TI - An introduction to Mendelian randomization with applications in neurology.
AB - Mendelian randomization studies have become increasingly common due to the
maturation of genome-wide association studies and its potential to ascertain
causal relationships. With the increasing use of this method comes the need for
medical practitioners and clinicians to develop an understanding of its
rationale, limitations, and interpretation. Mendelian randomization attempts to
ascertain a causal relationship between some risk factor of interest and some
outcome or disease of interest. It exploits Mendel's law on the random assortment
of genetic variants. This random assortment of genetic variants mimics the main
principle of randomization used in clinical trials; with the genetic variant
replacing the randomly allocated treatment. In this paper we provide a readable
introduction to the rationale behind Mendelian randomization and its limitations.
We also discuss and interpret several examples of Mendelian randomization
analyses which pertain to neurological diseases.
PMID- 29960143
TI - Differential influence of molybdenum and tungsten on the growth of barley
seedlings and the activity of aldehyde oxidase under salinity.
AB - The influence of molybdenum, tungsten on germination and growth of barley Hordeum
vulgare L. was studied. Results of this study revealed the differential effect of
heavy metals on seedlings growth. Exogenous molybdenum treatment stimulated the
growth of seedlings. The addition of the metal significantly stimulated root
elongation. Contrastingly, the addition of tungsten resulted in increased seed
germination and inhibits the growth of seedlings. The negative effect of tungsten
on the growth of barley was more profound for roots of plants. In addition, the
influence of metals on the growth of plants was also tested in saline conditions.
It is shown that under salinity stress plant growth drastically decreased in
presence of tungsten. Results of this study showed that activity of molybdenum
containing aldehyde oxidase (AO; EC 1.2.3.1) was also significantly affected by
metals. The activity of AO in leaves and roots enhanced with increasing
concentrations of molybdate, while tungstate treatment inhibited the enzyme
activity. Perhaps, the differential influence of molybdenum and tungsten on the
growth of barley is a direct effect of metals on aldehyde oxidase activity in
plants. Moreover, the intense negative effect of tungsten treatment on barley
growth under salinity conditions emphasizes an important role of aldehyde oxidase
in plant resistance to stress factors.
PMID- 29960144
TI - Socioeconomic inequality in maternal healthcare: An analysis of regional
variation in Bangladesh.
AB - Socioeconomic inequality in the utilisation of maternal healthcare services is
well-documented in Bangladesh. However, the spatial dimension of this inequality
is largely unexplored in the literature. This study examined the regional
variation of wealth-related inequality in the utilisation of maternal healthcare
services using data from Bangladesh Demographic and Health Survey, 2014. The
highest extent of pro-wealthy inequality was found in Chittagong and Sylhet for
ANC services compared to Khulna and Rangpur where inequality was the lowest. Pro
wealthy inequality was the lowest in Rangpur while Dhaka and Barisal tended to
have the greatest degree of inequality for delivery care services. Policy efforts
aiming to tackle socioeconomic inequality in maternal healthcare should consider
this spatial dimension of inequality in Bangladesh.
PMID- 29960145
TI - Accelerated PET kinetic maps estimation by analytic fitting method.
AB - In this work, we propose and test a new approach for non-linear kinetic
parameters' estimation from dynamic PET data. A technique is discussed, to derive
an analytical closed-form expression of the compartmental model used for kinetic
parameters' evaluation, using an auxiliary parameter set, with the aim of
reducing the computational burden and speeding up the fitting of these complex
mathematical expressions to noisy TACs. Two alternative algorithms based on
numeric calculations are considered and compared to the new proposal. We perform
a simulation study aimed at (i) assessing agreement between the proposed method
and other conventional ways of implementing compartmental model fitting, and (ii)
quantifying the reduction in computational time required for convergence. It
results in a speed-up factor of ~120 when compared to a fully numeric version, or
~38, with respect to a more conventional implementation, while converging to very
similar values for the estimated model parameters. The proposed method is also
tested on dynamic 3D PET clinical data of four control subjects. The results
obtained supported those of the simulation study, and provided input and
promising perspectives for the application of the proposed technique in clinical
practice.
PMID- 29960146
TI - Highly deleterious variations in COX1, CYTB, SCG5, FK2, PRL and PGF genes are the
potential adaptation of the immigrated African ostrich population.
AB - Because of variable inconvenient living conditions in some places around the
world, it is difficult to collect reliable physiological data for ostriches.
Therefore, this study aims to provide a comprehensive in silico insight for the
nature of polymorphism of important genetic loci that are related to
physiological and reproductive traits. Sixty-nine mature ostriches ranging over
half of Iraq were screened. Six exonic genetic loci, including cytochrome c
oxidase I (COX1), cytochrome b (CYTB), secretogranin V (SCG5), feather keratin 2
like (FK2), prolactin (PRL) and placenta growth factor (PGF) were genotyped by
PCR-single stranded conformation polymorphism (SSCP). Thirty-six novel SNPs,
including seventeen nonsynonymous (ns) SNPs, were observed. Several computational
software programs were utilized to assess the extent of the nsSNPs on their
corresponding proteins structure, function and stability. The results showed
several deleterious functional and stability changes in almost all the proteins
studied. The total severity of each missense mutation was evaluated and compared
with other nsSNPs accumulatively. It is evident from the extensive cumulative in
silico computation that both p.E34D and p.E60K in PGF have the highest
deleterious effect. The cumulative predictions from the present study are an
impressive guide for the genotypes of African ostriches, which bypassed the
expensive protocols for wet laboratory screening, to identify the effects of
variants. To the best of our knowledge, this is the first investigation of its
kind on the analyses and prediction outcome of missense mutations in African
ostrich populations. The highly deleterious nsSNPs in the placenta growth factor
are possible adaptive mutations which might be associated with adaptation in
extreme and new environments. The flow and protocol of the computational
predictions can be extended for various wild animals to identify the molecular
nature of adaptations.
PMID- 29960147
TI - The association of affective disorders and facial scarring: Systematic review and
meta-analysis.
AB - BACKGROUND: Facial scarring can have a dramatic effect on a patient's
psychological health and wellbeing and present unique management challenges. This
patient population remains poorly characterised in the contemporary literature.
AIMS: To evaluate the prevalence of, and risk factors associated with affective
disorders in adult patients with facial scars. METHODS: A systematic review was
conducted using a protocol registered with PROSPERO and in line with the PRISMA
statement. A comprehensive search of the literature was conducted using PubMed,
MEDLINE, EMBASE, PSYCHInfo and The Cochrane Library. RESULTS: Twenty one studies
were included, with a total of 2,394 participants. Using a random effects model,
the weighted pooled prevalence of anxiety was 26.1% (95% CI 17.9%-36.3%) and the
weighted pooled prevalence of depression was 21.4% (95% CI 15.4%-29.0%). Studies
identified female gender, past psychiatric history and violent causation as
factors associated with anxiety and depression. LIMITATIONS: Included studies
were limited to those published in peer reviewed journals. Longitudinal trends in
both anxiety and depression were limited by a short duration of follow up.
CONCLUSIONS: There is a high and persistent burden of affective disorders in
patients with facial scars. Additional research is required to further
characterise this population and develop effective management strategies.
PMID- 29960148
TI - PDK1 regulates definitive HSCs via the FOXO pathway during murine fetal liver
hematopoiesis.
AB - PDK1 (phosphoinositide dependent kinase-1) plays an important regulatory role in
B cells, T cells and platelets. Less is known about how PDK1 acts in
hematopoietic stem cells (HSCs), especially in the fetal liver (FL) during
embryonic hematopoiesis, as the FL is the primary fetal hematopoietic organ and
the main site of HSC expansion and differentiation. Here, we deleted the PDK1
gene in hematopoietic cells by crossing Vav-Cre transgenic mice with PDK1f/f
mice. Using a transplantation assay, we found that HSCs from the E15.5 FL of Vav
Cre;PDK1f/f embryos are severely impaired compared when compared with HSCs from
PDK1f/f or PDK1f/+ FLs. Additionally, we found that there were more FL HSCs in an
apoptotic state and active cell cycle in PDK1-deficient embryos than in control
embryos. By comparing the expression profiles of FL-derived LSKs in Vav
Cre;PDK1f/f embryos to the controls, we found that the BH3-only protein PUMA and
the cyclin family proteins were expressed higher in the Vav-Cre;PDK1f/f group,
which may account for the increased apoptosis and activated cell cycle in the
deficient HSCs. Furthermore, we demonstrated that the expression of FoxO3a was
higher in PDK1-deficient LSKs, indicating that the Akt-FoxO3a-PUMA axis may
participate in regulating LSKs apoptosis in the E15.5 FL. In contrast, FoxO1
expression was lower in PDK1-deficient LSK cells, suggesting that Akt-FoxO1-CCND
may regulate the HSC cell cycle. Taken together, our findings support a critical
role for PDK1 in maintaining FL hematopoiesis via regulating apoptosis and cell
cycle of definitive hematopoiesis by the Akt-FOXO signaling pathways.
PMID- 29960149
TI - Generation of two isogenic human induced pluripotent stem cell lines from a 15
year-old female patient with MERRF syndrome and A8344G mutation of mitochondrial
DNA.
AB - MERRF syndrome is predominantly caused by A8344G mutation in the mitochondrial
DNA (mtDNA), affecting MT-TK gene, which impairs the mitochondrial electron
transport chain function. Here, we report the generation of two isogenic induced
pluripotent stem cell (iPSC) lines, TVGH-iPSC-MRF-Mlow and TVGH-iPSC-MRF-Mhigh,
from the skin fibroblasts of a female MERRF patient harboring mtDNA A8344G
mutation by using retrovirus transduction system. Both cell lines share the same
genetic background except containing different proportions of mtDNA with the
A8344G mutation. Both cell lines exhibited the pluripotency and capacity to
differentiate into three germ layers.
PMID- 29960150
TI - Synthesis and biological characterization of organoruthenium complexes with 8
hydroxyquinolines.
AB - In this study we report the synthesis, characterization and a thorough biological
evaluation of twelve organoruthenium-8-hydroxyquinolinato (Ru-hq) complexes. The
chosen hqH ligands bear various halogen atoms in different positions which
enables to study effect of the substituents on physico-chemical and biological
properties. The determined crystal structures of novel complexes expectedly show
the cymene ring, a bidentately coordinated deprotonated hq and a halide ligand
(chlorido or iodido) coordinated to the ruthenium central ion. In previous
studies the anticancer potential of organoruthenium complex with 8
hydroxyquinoline ligand clioquinol was well established and we have decided to
perform an extended biological evaluation (antibacterial and antitumor activity)
of the whole series of halo-substituted analogs. Beside the cytotoxic potential
of studied compounds also the effect of two selected complexes (9 and 10) on
apoptosis induction in MG-63 and A549 cells was also studied via externalization
of phosphatidylserine at the outer plasma membrane leaflet. Both selected
complexes that gave best preliminary cytotoxicity results contain bromo
substituted hq ligands. Apoptosis induction results are in agreement with the
cell viability assays suggesting the higher and more selective anticancer
activity of complex 10 in comparison to complex 9 on MG-63 cells.
PMID- 29960151
TI - It's craving time: time of day effects on momentary hunger and food craving in
daily life.
AB - OBJECTIVE: A key determinant of food intake besides hunger is food craving, which
refers to an intense desire to consume a specific food. Although they commonly co
occur, they are conceptually different and their dissociation is thought to
underlie unhealthy eating (e.g., eating in the absence of hunger). To date, we
know almost nothing about their coherence (or dissociation) in daily life or
about the role of time of day and different food types. METHODS: The present
investigation assessed both hunger and food craving for several food categories
in daily life using smartphone-based ecological momentary assessment. Across
three independent studies (n = 50, n = 51, and n = 59), participants received
five or six prompts a day and reported their momentary hunger and desire for
tasty food (a subcomponent of food craving). RESULTS: Consistent across studies,
hunger and desire for tasty food exhibited largely similar patterns throughout
the day with two peaks (roughly corresponding to lunch and dinner). Examining
more specific food categories, study 3 found that although desire for main meal
type foods had a two-peak pattern in coherence with hunger, this pattern was
different for snack-type foods: Desire for fruits decreased, whereas desire for
sweets and salty snacks increased throughout the day with less coherence with
hunger. CONCLUSIONS: These findings suggest that dissociations between hunger and
craving are found only for snack-type foods, whereas hunger and general food
cravings cohere strongly. Interventions addressing snacking may take these
circadian patterns of food cravings into account.
PMID- 29960152
TI - Dairy products and chronic kidney disease: protective or harmful? asystematic
review of prospective cohort studies.
AB - OBJECTIVE: Evidence on the relationship between food sources of protein and
progressive decline in renal function in the general population is still
controversial. Among the protein-rich foods, dairy products have gained a lot of
attention in research on the prevention of metabolic disorders. This systemic
review attempted to summarize the findings of prospective cohort studies on the
relationship between dairy foods and incident chronic kidney disease (CKD) in the
general population. METHODS: The PubMed, Embase, Scopus, and Web of Science
databases were searched from inception up to January 2018 with no restriction on
the language of publication. Studies conducted in the general population with
consumption of dairy foods as the exposure of interest and with incident CKD
and/or decline in renal function as the study outcome were eligible for inclusion
in the review. RESULTS: Of the 391 articles that were extracted through database
searching, 7 were included in the review. Of the seven studies, five reported a
protective association for dairy consumption, particularly low-fat dairy, against
incident CKD or rapid decline in renal function; however, two studies did not
find such an association. CONCLUSION: Despite the limited studies on this topic,
findings from the available reports are generally in favor of a positive
association between dairy and renal health in the general population. However,
further studies are needed to replicate this finding and to determine whether
this relationship could be influenced by the fat content and/or the dairy
subtypes.
PMID- 29960153
TI - Arginine administration increases circulating endothelial progenitor cells and
attenuates tissue injury in a mouse model of hind limb ischemia/reperfusion.
AB - OBJECTIVE: This study investigated whether the administration of L-Arginine, the
precursor of nitric oxide, increases the percentages of blood endothelial
progenitor cells and protects against ischemia/reperfusion induced inflammatory
response in a mouse model of hind-limb IR injury. METHOD: C57BL/6 mice were
randomized to one normal-control and four ischemia/reperfusion groups. The normal
control group did not undergo an ischemia/reperfusion procedure but mice in the
ischemia/reperfusion groups were subjected to 150 min of unilateral hind-limb
ischemia. The ischemia/reperfusion groups were subjected to either intravenous
saline or L-Arginine (300 mg/kg body weight) administration before reperfusion
and then sacrificed at either 24 h or 48 h after reperfusion. Blood and muscle
tissues were collected for analysis. RESULTS: Ischemia/reperfusion injury led to
a significant decrease in the percentage of blood endothelial progenitor cells
and plasma nitric oxide concentration but plasma interleukin-6 levels and gene
expression of inflammatory cytokines in injured muscle tissue were elevated. In
contrast to the saline groups, those with L-Arginine administration were able to
maintain a normal level of blood endothelial progenitor cells. In addition, after
reperfusion, concentrations of nitric oxide, matrix metallopeptidase-9, and
vascular endothelial growth factor in plasma were upregulated but keratinocyte
derived chemokine and monocyte chemoattractant protein-1 messenger RNA
expressions in muscle were attenuated 48 h after reperfusion. Histologic findings
also demonstrated a significant reduction of ischemia/reperfusion-induced muscle
injury when L-Arginine was administered. CONCLUSION: A single dose of L-Arginine
administration before reperfusion increases the percentage of endothelial
progenitor cells and reduces the inflammatory reaction locally and systemically
after ischemia/reperfusion injury.
PMID- 29960154
TI - Antioxidant activity from extra virgin olive oil via inhibition of hydrogen
peroxide-mediated NADPH-oxidase 2 activation.
AB - OBJECTIVES: Extra virgin olive oil (EVOO) supplementation is associated with a
significant reduction in cardiovascular disease but the underlying mechanism is
still unclear. METHODS: In platelets that were taken from healthy subjects (n =
5), agonist-induced hydrogen peroxide (H2O2) production and NADPH oxidase 2
(NOX2) activation in the presence of or without catalase, which catabolizes H2O2,
were investigated. Platelet H2O2 production, NOX2 activation, EVOO vitamin E, and
total polyphenols as well as EVOO's ability to scavenge H2O2 were also measured.
RESULTS: Platelet NOX2 activation and H2O2 production were significantly
inhibited in catalase-treated platelets and platelets that were incubated with
five different EVOOs. The EVOO content of vitamin E was 53 to 223 mg/kg and total
polyphenols 145 to 392 mg/L Gallic acid equivalent. EVOOs quenched in vitro H2O2
by 39 to 62%, which is an effect that is significantly correlated with vitamin E
and total polyphenol concentrations (R = 0.688; P <0.001 and R = 0.541; P <0.001,
respectively). CONCLUSIONS: This in vitro study provides the first evidence that
EVOO downregulates platelet H2O2 and in turn NOX2 activity via H2O2 scavenging.
PMID- 29960155
TI - Television advertising of food during children's programming in Nepal.
AB - OBJECTIVE: The World Health Organization has recommended that advertising of
unhealthy food to children decrease in quantity (exposure) and efficacy (power).
The degree to which marketing practices align with these recommendations varies
across countries. The purpose of this study is to describe the television food
marketing landscape that children experience in the South Asian country of Nepal.
RESEARCH METHODS & PROCEDURES: Commercials from 57hours of television were
recorded from three channels during hours that children's programming was played.
In a content analysis of 1,203 food commercials, researchers coded commercials
for nutrition content, product category and marketing appeal type. RESULTS:
Principal findings of this study were that nearly 21% of airtime during
children's programming was dedicated to commercials, and 55% of that was
dedicated to foods. Over 70% of food commercials aired advertised foods with
excessive amounts of saturated fat, sugar, and/or sodium; nearly half of the
commercials (47.7%) featured products that contained excess sugar. The most
prevalent food types shown were ice cream and popsicles (20.7%),
energy/nutritional supplements (20.6%), and candy (14.7%). Additionally, the
three most commonly occurring marketing appeals featured highly-efficacious
strategies for persuading children-animated effects (83.2%), movie, cartoon,
animated, or costumed characters (36.8%), and television/movie tie-ins (16.5%).
CONCLUSION(S): Results from this study suggest that many television commercials
shown in Nepal do not meet WHO recommendations for advertising foods to children.
This is likely to negatively impact the diet and health of the next generation of
Nepalis.
PMID- 29960156
TI - Intravenous lipid emulsions and liver function in adult chronic intestinal
failure patients: results from a randomized clinical trial.
AB - AIM: Intravenous lipid emulsion (ILE) can become a risk factor for intestinal
failure associated liver disease (IFALD). Many ILEs are commercially available,
however, a direct comparison of their impact on liver has, to our knowledge,
never been performed. The aim of the study was to analyse that clinical problem
during long term parenteral nutrition (PN). METHODS: A randomized, controlled
clinical trial was performed at the Intestinal Failure Center in Skawina, Poland.
Sixty-seven patients (37 F, 30 M, mean age 53.9 years) enrolled in home
parenteral nutrition (HPN) due to stable chronic intestinal failure (CIF) were
randomized to receive one the following for 12 months: long-chain triglycerides
(LCT), medium/long-chain triglycerides, olive oil/LCT (OO/LCT) and a mix of
LCT/MCT/OO/fish oil. Clinical evaluation and biochemical tests (total bilirubin,
SGOT, SGTP, GGPT, alkaline phosphatase) were performed at enrolment and after 6
and 12 months. RESULTS: the most common reason for intestinal failure (IF) was
short bowel due to mesenteric ischaemia, followed by Crohn's disease, surgical
complications and radiation enteritis. PN stabilized liver parameters in all
patients. No essential fatty acids deficiency was diagnosed. All four ILEs
demonstrated comparable influence on liver in all study periods. The only
exception was the decrease in total bilirubin concentration after 12 months (28.1
+/- 25.3vs 11.1 +/- 4.5, p = 0.0023) and GGTP (222.5 +/- 205.8vs 146.6 +/- 197.7,
p = 0.0079) when OO/LCT was in use. CONCLUSIONS: All four ILEs tested may be safe
even during long-term parenteral nutrition. OO/LCT may be more effective than the
others, but more studies in the field are needed.
PMID- 29960157
TI - Prevalence of sarcopenia in systemic sclerosis: assessing body composition and
functional disability in patients with systemic sclerosis.
AB - OBJECTIVE: We analyzed the prevalence of sarcopenia among systemic sclerosis
(SSc) patients with respect to quality of life, disability, organ involvement,
and muscle function. METHODS: A total of 129 patients who met the ACR/EULAR 2013
classification criteria were included. Body composition was measured using
bioelectric impedance analysis. Sarcopenia was defined according to the criteria
of the European Working Group on Sarcopenia in Older People. Handgrip and knee
extension strength and pulmonary peak flow were measured. Physical function was
assessed with the Short Form-36 Health Survey and Scleroderma Health Assessment
Questionnaire. RESULTS: Sarcopenia was prevalent in 22.5% of patients. There were
significant differences between patients with and without sarcopenia regarding
handgrip strength (11.5 [2.0-30.0] versus 18.0 [1.0-41.0] kilogram force [kgf]; P
<0.001) and knee extension strength (11.0 [3.5-32.5] versus 17.5 [3.5-88.0] kgf;
P = 0.006), physical function (38.8 [9.9-85.0] versus 48.8 [0-88.0]; P = 0.032)
and number of immunosuppressants (2 [0-4] versus 1 [0-5]; P = 0.009). There were
no differences regarding age (57.0 [32.0-83.0] versus 60.5 [28.0-82.0] years; P =
0.350) and disease duration (8 [1-27] versus 7 [0-34] years; P = 0.350).
CONCLUSIONS: Sarcopenia is common in patients with SSc and is associated with
physical impairment that affects everyday life and participation in work.
Interestingly, although age is the main risk factor for sarcopenia in the general
population, it did not differ between sarcopenic and non-sarcopenic SSc patients
in our study. Instead, the number of immunosuppressive drugs was significantly
higher among sarcopenic patients.
PMID- 29960158
TI - Inflammatory potential of diet is associated with cognitive function in an older
adult Korean population.
AB - OBJECTIVE: To examine the association between the inflammatory potential of diet
and the quality of cognitive function in an older adult Korean population.
METHODS: A total of 239 participants (88 men and 151 women) ages >=65 y were
selected from various health centers in Korea. To assess the inflammatory
potential of diet, Energy-adjusted Dietary Inflammatory Index (E-DII) scores were
computed based on a single 24-h recall. Cognitive function was assessed using the
Korean Mini-Mental State Examination. Multiple linear and logistic regression
models were fit to estimate the association between E-DII scores and the degree
of cognitive function. RESULTS: E-DII scores were significantly inversely
associated with Korean Mini-Mental State Examination score in both unadjusted and
adjusted models, after controlling for sex, age, body mass index, sleep hours,
supplement use, education level, self-reported health conditions, history of
dementia, and physical activity (beta = -1.33, 95% confidence interval [CI] =
1.95, -0.71, P <0.0001; beta = -0.58, 95% CI = -1.11, -0.06, P = 0.03,
respectively). Participants in the highest E-DII tertile had increased risk for
mild or moderate cognitive impairment compared with those in the lowest E-DII
tertile (adjusted odds ratio 6.32, 95% CI 1.18-33.78; P for trend = 0.0031).
CONCLUSIONS: Higher E-DII scores were associated with increased risk of cognitive
impairment, suggesting that consuming a proinflammatory diet is associated with
increased risk for cognitive impairment in the older Korean adults.
PMID- 29960159
TI - Caffeic acid ameliorates hepatic steatosis and reduces ER stress in high fat diet
induced obese mice by regulating autophagy.
AB - OBJECTIVE: Non-alcoholic fatty liver disease is characterized by high hepatic
triacylglycerol contents, which is associated with endoplasmic reticulum (ER)
stress and insulin resistance. Caffeic acid (CA) has antioxidant,
immunomodulatory, and antiinflammatory effects. We investigated the effects of CA
on hepatic steatosis and its mechanism of action. METHODS: We treated CA (50 uM)
with AML12 cells. We categorized mice into three groups as follows: low-fat diet
mice (LFD, n = 10), high-fat diet-induced obese mice (HFD, n = 10), and HFD fed
with CA (50 mg/kg/d, n = 10) for 10 wk. RESULTS: CA did not cause any cytotoxic
effect on AML12 cell line within the range of concentrations tested (0-200 uM).
We found that CA (50 uM) treatment in palmitate-treated AML12 hepatocytes reduced
lipid accumulation and lipogenesis markers, decreased ER stress, and increased
autophagy markers. However, there was no significant difference in lipid droplets
of palmitate-treated AML12 hepatocytes and CA-treated autophagy-related protein 7
deficiency AML12 hepatocytes with palmitate. Similarly, CA significantly lowered
body and liver weights. Lipid accumulation in the liver decreased in the HFD + CA
group compared with the HFD group. Glucose intolerance and insulin sensitivity
also were markedly improved in the HFD + CA group. Moreover, the levels of ER
stress markers were decreased in the livers of the HFD + CA group. CONCLUSION:
Autophagy markers were increased in the livers of the HFD + CA group. These
results suggest that caffeic acid may ameliorate hepatic steatosis and decrease
ER stress by increasing autophagy.
PMID- 29960160
TI - Lipid profile associated with the systemic inflammatory response syndrome and
sepsis in critically ill patients.
AB - OBJECTIVES: Changes in lipid profiles occur in systemic inflammatory response
syndrome (SIRS), whether due to sepsis or another cause. Hypocholesterolemia
associated with hypertriacylglycerolemia can lead to disease severity and higher
mortality. The aim of this systematic review was to describe the principal
alterations in markers that participate in the alteration of the lipid profile.
METHODS: We reviewed articles focused on alterations in the lipid profile in
SIRS, sepsis, or both that were indexed in the Scientific Electronic Library
Online from 2000 to 2017. The descriptors used were SIRS; sepsis; lipid profile;
and lipoproteins. We focused in particular on the relationships among SIRS,
sepsis, and lipid profiles. RESULTS: We included 29 studies that discussed
decreased high-density lipoprotein (HDL), total cholesterol, and low-density
lipoprotein, and elevated triacylglycerols concentrations in patients with SIRS,
sepsis, or both. The variation in the lipid profile was proportional to the level
of inflammation as evaluated by inflammatory markers, including C-reactive
protein, interleukin-6 and interleukin-8, lipopolysaccharide-binding protein, and
tumor necrosis factor. Additionally, there was a change in the composition of
lipoproteins, especially HDL, triacylglycerols, and very low-density lipoprotein.
HDL appears to be an inflammatory marker, as reduction of its levels reflects the
intensity of the underlying inflammatory process. CONCLUSION: Critically ill
patients with SIRS, sepsis, or both presented with alterations in lipid
metabolism.
PMID- 29960161
TI - Should we calculate or measure energy expenditure? practical aspects in the ICU.
AB - Indirect calorimetry is currently a gold standard of resting energy expenditure
(REE) assessment in critically ill patients. Many predictive equations of energy
expenditure have been proved to imprecisely predict REE and lead to under- or
overfeeding. The benefits of indirect calorimetry-guided nutrition therapy rather
than calculation-based strategy have been demonstrated in randomized controlled
trials. To minimize energy debt in the intensive care unit, we support early
enteral feeding. REE should be measured as soon as the patient's conditions allow
and the target of delivered calorie should be around 0.7 to 1 of measured REE to
avoid overfeeding. The supplemental parenteral nutrition should be prescribed to
close the caloric gap if the goal is not reached by enteral nutrition alone.
PMID- 29960162
TI - Carnosine as malondialdehyde scavenger in stallion seminal plasma and its role in
sperm function and oxidative status.
AB - Semen biotechniques may impair sperm quality due to excessive production of
reactive oxygen species (ROS). Additionally, products of the oxidative reaction,
especially involving lipids (e.g., malondialdehyde - MDA), may be even more
harmful to sperm. Carnosine, previously reported to be present in seminal plasma
of several species, may be a key factor on sperm tolerance to biotechniques by
counterattacking the deleterious influence of MDA. Therefore, the aim of this
study was to measure the levels of carnosine present in equine seminal plasma and
relate these findings with sperm function and oxidative status during cooling and
cryopreservation. Thus, semen samples were collected from 40 stallions in
duplicate (N = 80) and then submitted to cooling and cryopreservation. Samples
were then allocated into groups of high and low tolerance to refrigeration and
cryopreservation (bad cooler and good cooler/bad freezer and good freezer,
respectively), and in groups of different concentrations of carnosine (High,
Medium-high, Medium-low and Low carnosine). Samples were evaluated for sperm
kinetics patterns, function of sperm structures and oxidative status. In good
cooler samples, it was observed higher concentrations of carnosine (Good cooler:
224.98 +/- 19.16 ng/mL; Bad cooler: 159.72 +/- 15.99 ng/mL; p = 0.0056), ROS
production (Good cooler: 26.40 +/- 18.33%; Bad cooler: 18.33 +/- 1.84%; p =
0.001) and lipid peroxidation rates (Good cooler: 193.23 +/- 18.22 ng/mL; Bad
cooler: 131.92 +/- 12.25; p = 0.0064). Groups of samples with higher carnosine
concentrations had lower levels of malondialdehyde (High: 79.33 +/- 6.72 ng/mL;
Medium-high: 140.45 +/- 11.70 ng/mL; Medium-low: 202.57 +/- 16.30 ng/mL and Low:
231.02 +/- 32.35 ng/mL; p < 0.05), demonstrating that carnosine was effective in
removing lipid peroxidation products. Due to the removal of seminal plasma during
the cryopreservation process, no differences occurred in carnosine levels between
bad and good freezer groups. In this context, this study provides relevant data
for future therapies using carnosine during cryopreservation, aiming to replace
the levels lost due to the necessary removal of seminal plasma.
PMID- 29960163
TI - Effects of melatonin implants on the reproductive performance and endocrine
function of camel (Camelus dromedarius) bulls during the non-breeding and
subsequent breeding seasons.
AB - This study aimed to evaluate the effects of melatonin implants on the
reproductive performances and hormone levels of dromedary (Camelus dromedarius)
bulls during the non-breeding and subsequent breeding seasons. Fourteen mature
dromedary bulls were divided into a control group (n = 7) and a group that was
implanted with melatonin (n = 7) twice, at the beginning of the study and 35 days
later. The trial started on the 17th June and continued for 10 weeks during the
non-breeding season. Reproductive performances of animals in the control and
melatonin groups were evaluated weekly during the non-breeding season [control
non-breeding (CNB) and melatonin non-breeding (MNB) groups, respectively] and
evaluated again during the subsequent breeding season [control breeding (CB) and
melatonin breeding (MB) groups, respectively], which started on the 6th December
and continued for 10 weeks. MNB bulls had greater (P <= 0.05) scrotum
circumference and testicular volume, sexual desire, reaction time and mating
ability scores, and serum melatonin and testosterone concentration values (24.91
+/- 0.26 cm, 271.00 +/- 7.81 cm3, 2.31 +/- 0.13, 2.03 +/- 0.22, 2.26 +/- 0.09,
23.90 +/- 0.05 pg/mL and 2764.51 +/- 137.02 pg/mL, respectively) than the CNB
group (23.63 +/- 0.05 cm, 199.21 +/- 3.27 cm3, 1.00 +/- 0.00, 0.00 +/- 0.00, 1.00
+/- 0.00, 9.46 +/- 0.08 pg/mL and 1872.41 +/- 264.89 pg/mL, respectively). The
scrotum and testes, reaction time score, proportion of bulls refusing to mount,
and serum melatonin values were significantly higher in MB than CB bulls (P <=
0.05). Progressive motility (PM), average pathway velocity, straight-line
velocity, curvilinear velocity (VCL), linearity, straightness (STR), wobble, beat
cross frequency (BCF), livability, and DNA integrity were significantly higher in
MB than CB bulls (P <= 0.05). PM, VCL, STR, amplitude of lateral head
displacement, BCF, and livability were significantly higher in MNB than CB bulls
(P <= 0.05). In conclusion, melatonin implants improved the reproductive
performance of bulls during the non-breeding and subsequent breeding seasons.
PMID- 29960164
TI - Luteinizing hormone upregulates NPPC and downregulates NPR3 mRNA abundance in
bovine granulosa cells through activation of the EGF receptor.
AB - During folliculogenesis, the luteinizing hormone (LH) surge triggers dynamic
events in granulosa cells that culminate with ovulation. The aim of this study
was to evaluate if the epidermal growth factor receptor (EGFR) is required for
ovulation in cattle, and if it regulates the expression of the natriuretic
peptide (NP) system in granulosa cells after gonadotropin-releasing hormone
(GnRH)/LH stimulation. It was observed that GnRH induces amphiregulin (AREG) and
epiregulin (EREG) mRNA at 3 and 6 h after in vivo treatment, but the expression
of these genes was not regulated by atrial (ANP) and C-type (CNP) NPs in
granulosa cells cultured in vitro. The abundance of mRNA encoding the NP
receptors (NPR1, 2 and 3) was not altered by LH supplementation and/or EGFR
inhibition (AG1478; AG) in granulosa cells after 6 h of in vitro culture.
However, in the same conditions, mRNA encoding the natriuretic peptide precursor
C (NPPC) was upregulated by LH, whereas AG (0.5 and 5 MUM) inhibited the LH
effect. In order to confirm those results, 5 MUM AG or saline were
intrafollicularly injected in preovulatory follicles and cows were simultaneously
treated with GnRH intramuscularly. Granulosa cells harvested at 6 h after GnRH
injection revealed higher NPR3 and lower NPPC mRNA levels in AG-treated, compared
to control cows. However, intrafollicular injection of AG did not inhibit GnRH
induced ovulation. In granulosa cells cultured in vitro, ANP associated with LH
increased prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA abundance. In
conclusion, we inferred that LH modulated NPPC and NPR3 mRNA abundance through
EGFR in bovine granulosa cells, but ovulation in cattle did not seem to depend on
EGFR activation.
PMID- 29960165
TI - The time-course of cortical responses to speech revealed by fast optical imaging.
AB - Recent work has sought to describe the time-course of spoken word recognition,
from initial acoustic cue encoding through lexical activation, and identify
cortical areas involved in each stage of analysis. However, existing methods are
limited in either temporal or spatial resolution, and as a result, have only
provided partial answers to the question of how listeners encode acoustic
information in speech. We present data from an experiment using a novel
neuroimaging method, fast optical imaging, to directly assess the time-course of
speech perception, providing non-invasive measurement of speech sound
representations, localized to specific cortical areas. We find that listeners
encode speech in terms of continuous acoustic cues at early stages of processing
(ca. 96 ms post-stimulus onset), and begin activating phonological category
representations rapidly (ca. 144 ms post-stimulus). Moreover, cue-based
representations are widespread in the brain and overlap in time with graded
category-based representations, suggesting that spoken word recognition involves
simultaneous activation of both continuous acoustic cues and phonological
categories.
PMID- 29960166
TI - ROS mediated ER stress induces Bax-Bak dependent and independent apoptosis in
response to Thioridazine.
AB - A dopamine receptor antagonist, Thioridazine (TDZ) is known for its cytotoxic
activity against various cancers and its role in combinational chemotherapy is
being actively investigated. Several molecular targets of TDZ have been studied
to delineate its anticancer activities, with contrasting findings in different
cancer types. Moreover, the underlying mechanism of cell death from TDZ treatment
is not well defined. In the current study, we studied TDZ mediated cell death
mechanism employing cervical cancer cells. TDZ treatment induced nuclear
condensation, mitochondrial membrane potential loss, mitochondrial cytochrome c
release, activation of caspase-9 and caspase-3 substantiating mitochondrial
pathways of apoptosis in cells. TDZ induced ROS generation and up-regulation of
ER stress linked proteins, such as CHOP, BiP etc. ER stress and apoptosis caused
by TDZ were prevented by ROS inhibitor N-acetyl-L-cysteine (NAC) and protein
synthesis inhibitor cycloheximide. In TDZ mediated cytocidal cellular process,
autophagy acted as a cell survival factor as the inhibition of autophagy by 3
Methyladenine resulted in increased cell death. TDZ induced apoptosis was
associated with decreased Bcl-2 expression and the overexpression of Bcl-2
resulted in inhibition of apoptosis. Studies in Bax-Bak knock-out cell model
indicated that TDZ trigger both the Bax-Bak dependent and independent apoptosis
through ROS. In the presence of Bax and Bak, cells are more sensitised to death
than in the absence of these proteins. Both Bax-Bak dependent and independent
apoptosis were significantly inhibited by ROS inhibitor NAC. Conclusively, TDZ
induced Bax-Bak dependent and independent apoptosis by enhancing ROS production
followed by ER stress.
PMID- 29960167
TI - Dexmedetomidine protects against lipopolysaccharide-induced sepsis-associated
acute kidney injury via an alpha7 nAChR-dependent pathway.
AB - Acute kidney injury (AKI) is a clinical syndrome that results in severe tubular
damage with high morbidity and mortality. However, there is a lack of effective
therapy strategies. Therefore, it is critical to develop effective drugs for AKI.
Dexmedetomidine (DEX), a highly selective alpha2-adrenoreceptor agonist, has
neuroprotective, anti-inflammatory and sympatholytic properties. The present
study aimed to investigate the effect DEX on attenuating the inflammatory
reaction and apoptosis in the kidney tissues of septic mice and to explore its
underlying mechanisms. Sepsis-induced AKI mice models were generated via
intraperitoneal injection of lipopolysaccaride (LPS). DEX reduced LPS-induced
local inflammation and tubular apoptosis, which was aggravated in the
pathogenesis of renal dysfunction. Reverse transcription-quantitative polymerase
chain reaction and western blot analysis results revealed that the expression of
pro-apoptotic genes and inflammatory factors were markedly reduced by DEX
pretreatment. Furthermore, the protective role of DEX was markedly inhibited by
the alpha7 nicotinic acetylcholine receptor (nAChR) antagonist alpha
bungarotoxin. These findings provided novel evidence for the anti-apoptotic and
anti-inflammatory effects of DEX in LPS-induced AKI mice through an alpha7 nAChR
dependent signaling pathway.
PMID- 29960168
TI - MiRNA-34a reversed TGF-beta-induced epithelial-mesenchymal transition via
suppression of SMAD4 in NPC cells.
AB - Epithelial-mesenchymal transition (EMT) is considered a prerequisite for tumor
invasion and metastasis in many cancers. However, the mechanisms underlying EMT
in nasopharyngeal carcinoma (NPC) is largely unknown. In this study, we found
that transforming growth factor-beta (TGF-beta), which reportedly promotes EMT in
multiple cancers, can trigger EMT and increase the invasive and migratory
capacities of NPC cells. Conversely, the downregulation of SMAD4, a vital member
of the canonical TGF-beta pathway, reversed the TGF-beta-induced EMT, invasion,
and migration. Further experiments revealed that SMAD4 was the target of miRNA
34a, which was downregulated in NPC tissues and suppressed NPC cell metastasis in
vivo. miRNA-34a overexpression also antagonized the TGF-beta-induced EMT
progression, invasion, and migration through SMAD4 inhibition. However, the
restoration of SMAD4 expression rescued the inhibitory effects of miRNA-34a on
tumorigenesis. All these results confirmed that miRNA-34a suppressed the TGF-beta
induced EMT, invasion, and migration of NPC cells by directly targeting SMAD4,
which indicated the potential of miR-34a as a therapeutic target against NPC.
PMID- 29960170
TI - Keeping secrets in the cloud: Mobile phones, data security and privacy within the
context of pregnancy and childbirth in Tanzania.
AB - Growing evidence points to the potential value of mobile phone-based technologies
('mHealth') to help strengthen community health systems in low- and middle-income
countries, but mHealth approaches also carry considerable risks with respect to
data security, individual privacy, and confidentiality. We examined the
perspectives of frontline community health workers and their female clients
regarding data security and privacy within the context of an mHealth intervention
to improve women's uptake of maternal health services from October 2013 to July
2014 in rural Tanzania. Qualitative findings demonstrate that the use of new
technologies to capture health service user data during pregnancy and childbirth
has both positive and negative impacts on perceptions of personal privacy and
confidentiality. Women's concerns regarding privacy aligned closely with a belief
that pregnancies and expected delivery dates must be kept secret, reflecting
fears that pregnancy renders women vulnerable to witchcraft by jealous neighbors.
Women also shared concerns that health workers' male partners could access their
private information. Strong community-based engagement is recommended from the
outset when developing a mHealth intervention to integrate beliefs and gender
dynamics that may influence acceptability and implementation of new technologies.
PMID- 29960169
TI - Angelica sinensis polysaccharide protects rat cardiomyocytes H9c2 from hypoxia
induced injury by down-regulation of microRNA-22.
AB - BACKGROUND: The cardioprotective role of Angelica sinensis has been proven in
previous studies. However, the effects of Angelica sinensis polysaccharide (ASP,
major bioactive component of Angelica sinensis) on myocardial infarction (MI)
remain unclear. This study aimed to investigate the effects of ASP on hypoxia
induced H9c2 cell injury as well as the underlying mechanisms. METHODS: We
constructed in vitro hypoxic model to mimic MI. Cell viability, proliferation and
apoptosis were respectively measured by using CCK-8 assay, Western blot analysis,
and flow cytometry assay/Western blot analysis, to evaluate cell injury after
treatments. The effects of ASP pretreatment on hypoxia-induced injury were
explored. Expression of miR-22 after treatments was determined by stem-loop RT
PCR, and whether ASP affected H9c2 cells via miR-22 was studied. Involvements of
the PI3K/AKT and JAK1/STAT3 pathways were finally explored. RESULTS: Hypoxia
induced decreases of cell viability and proliferation as well as increase of
apoptosis were attenuated by ASP pretreatments. Hypoxia treatment up-regulated
miR-22 expression, and the up-regulation was mitigated by ASP pretreatment.
Effects of ASP pretreatment on hypoxia-treated H9c2 cells were mitigated by miR
22 overexpression while were augmented by miR-22 inhibition. Phosphorylation
levels of PI3K, AKT, JAK1 and STAT3 were increased by ASP through down-regulating
miR-22 in hypoxia-treated H9c2 cells. CONCLUSION: ASP pretreatment attenuated
hypoxia-induced H9c2 cell injury, possibly through down-regulating miR-22
expression. The PI3K/AKT and JAK1/STAT3 pathways were activated by ASP
pretreatment via miR-22 in hypoxia-treated cells.
PMID- 29960171
TI - Ethnic and geographic variations in multimorbidty: Evidence from three large
cohorts.
AB - A common characteristic of patients seen at the Veterans Health Administration
(VHA) is a high number of concurrent comorbidities (i.e. multimorbidity). This
study (i) examines the magnitude and patterns of multimorbidity by race/ethnicity
and geography; (ii) compares the level of variation explained by these factors in
three multimorbidity measures across three large cohorts. We created three
national cohorts for Veterans with chronic kidney disease (CKD:n = 2,190,564),
traumatic brain injury (TBI:n = 167,954) and diabetes-mellitus (DM:n =
1,263,906). Multimorbidity was measured by Charlson-Deyo, Elixhauser and Walraven
Elixhauser scores. Multimorbidity differences by race/ethnicity and geography
were compared using generalized linear models (GLM). Latent class analysis (LCA)
was used to identify groups of conditions that are highly associated with
race/ethnic groups. Differences in age (CKD,74.5, TBI,49.7, DM, 66.9 years), race
(CKD,80.9%, TBI,76.4%, DM, 63.8% NHW) and geography (CKD,64.4%, TBI,70%, DM,
70.9% urban) were observed among the three cohorts. Accounting for these
differences, GLM results showed that risk of multimorbidity in non-Hispanic
blacks (NHB) with CKD were 1.16 times higher in urban areas and 1.10 times higher
in rural areas compared to non-Hispanic whites (NHW) with CKD. DM and TBI showed
similar results with risk for NHB, 1.05 higher in urban areas and 0.97 lower in
rural areas for both diseases. Overall, our results show that (i) multimorbidity
risk was higher for NHB in urban areas compared to rural areas in all three
cohorts; (ii) multimorbidity risk was higher for Hispanics in urban areas
compared to rural areas in the DM and CKD cohorts; and (iii) the highest overall
multimorbidity risk of any race group or location exists for Hispanics in insular
islands for all three disease cohorts. These findings are consistent among the
three multimorbidity measures. In fact, our LCA also showed that a three class LC
model based on Elixhauser or Charlson provides good discrimination by type and
extent of multimorbidity.
PMID- 29960172
TI - Navigating the evidentiary turn in public health: Sensemaking strategies to
integrate genomics into state-level chronic disease prevention programs.
AB - In the past decade, healthcare delivery has faced two major disruptions: the
mapping of the human genome and the rise of evidence-based practice. Sociologists
have documented the paradigmatic shift towards evidence-based practice in
medicine, but have yet to examine its effect on other health professions or the
broader healthcare arena. This article shows how evidence-based practice is
transforming public health in the United States. We present an in-depth
qualitative analysis of interview, ethnographic, and archival data to show how
Michigan's state public health agency has navigated the turn to evidence-based
practice, as they have integrated scientific advances in genomics into their
chronic disease prevention programming. Drawing on organizational theory, we
demonstrate how they managed ambiguity through a combination of sensegiving and
sensemaking activities. Specifically, they linked novel developments in genomics
to a long-accepted public health planning model, the Core Public Health
Functions. This made cutting edge advances in genomics more familiar to their
peers in the state health agency. They also marshaled state-specific surveillance
data to illustrate the public health burden of hereditary cancers in Michigan,
and to make expert panel recommendations for genetic screening more locally
relevant. Finally, they mobilized expertise to help their internal colleagues and
external partners modernize conventional public health activities in chronic
disease prevention. Our findings show that tools and concepts from organizational
sociology can help medical sociologists understand how evidence-based practice is
shaping institutions and interprofessional relations in the healthcare arena.
PMID- 29960173
TI - Attentional ERPs distinguish aging and early Alzheimer's dementia.
AB - The early detection of Alzheimer's disease requires our distinguishing it from
cognitive aging. Here, we test whether spatial attentional changes might support
that distinction. We engaged young normal (YN), older normal (ON), and patients
with early Alzheimer's dementia (EAD) in an attentionally cued, self-movement
heading discrimination task while we recorded push-button response times and
event related potentials. YNs and ONs show the behavioral effects of attentional
shifts from the cue to the target, whereas EAD patients did not (p < 0.001). YNs
and ONs also show the shifting lateralization of a newly described attentional
event related potentials component, whereas EAD patients did not (p < 0.001). Our
findings suggest that spatial inattention in EAD patients may contribute to
heading direction processing impairments that distinguish them from ONs and
undermine their navigational capacity and driving safety.
PMID- 29960174
TI - The perception of water related risks and the state of the water environment in
the European Union.
AB - In this work, we examine the factors predicting the perception of three distinct
risks, namely "Algae growth", "Chemical pollution" and "Changes to ecosystems",
to the water environment of each European Union Member State. We utilize a novel
dataset that combines a Europe-wide Eurobarometer poll on water-related issues
and a database of water quality indicators, water stressors and impacts compiled
for the European Environment Agency (EEA) under the Water Information System for
Europe (WISE). We utilize a three-level logistic regression model with the 2nd
and 3rd levels being the region and the country in which the respondent lives. We
find that perceived risks generally reflect the actual state of the environment
at both the regional and national level, with the national level being stronger.
Perceived risks are also related to socio-demographics, information and
knowledge, pro-environmental activity and consumer practices. The influence of
unobserved factors, captured in the model by random effects, was large at the
national level, reflecting differences in cultural and institutional structures".
Results support higher levels of water policy devolution and more focused and
targeted policy communication.
PMID- 29960175
TI - Remediation of sedimented fiber originating from pulp and paper industry:
Laboratory scale anaerobic reactor studies and ideas of scaling up.
AB - Anaerobic treatment of sedimented fibers collected from bottom of a bay that had
been receiving pulp and paper mill wastewater for about 70 years were studied for
the first time in semi-continuously fed continuously stirred tank reactors
(CSTR). Anaerobic treatment of the fiber sediment was shown to be feasible,
without dilution and with nitrogen and buffer supplement, at organic loading
rates (OLR) up to 2.5 kg VS/m3d and hydraulic retention times (HRT) of 60 d
resulting in methane yields of 201 +/- 18 L CH4/kg VS. Co-digestion of sedimented
fiber with sewage sludge at an OLR of 1.5 kg VS/m3d and HRT of 20 d resulted in a
methane production of 246 +/- 10 L CH4/kg VS. The techno-economic feasibility of
mono and co-digestion process together with several case dependent factors such
as maximum operable OLR, digestate utilization needs to be evaluated before
making further conclusions for larger scale remediation applications.
PMID- 29960176
TI - Optimal and objective placement of sensors in water distribution systems using
information theory.
AB - Optimization-based deployment of contamination warning system in water
distribution systems has been widely used in the literature, due to their
superior performance compared to rule- and opinion-based approaches. However,
optimization techniques impose an excessive computational burden, which in turn
is compensated for by shrinking the problem's decision space and/or using faster
optimization algorithms with less accuracy. This imposes subjectivity in
interpretation of the system and associated risks, and undermines model's
accuracy by not exploring the entire feasible space. We propose a framework that
uses information theoretic techniques, including value of information and
transinformation entropy, for optimal sensor placement. This can be used either
as pre-selection, i.e. pinpointing best potential locations of sensors to be in
turn used in optimization framework, or ultimate selection, i.e. single-handedly
selecting sensor locations from the feasible space. The proposed framework is
then applied to Lamerd water distribution system, in Fars province, Iran, and the
results are compared to the suggested potential locations of sensors in previous
studies and results of TEVA-SPOT model. The proposed information theoretic scheme
enhances the decision space, provides more accurate results, significantly
reduces the computational burden, and warrants objective selection of sensor
placement.
PMID- 29960177
TI - Faecal indicator organism inputs to watercourses from streamside pastures grazed
by cattle: Before and after implementation of streambank fencing.
AB - Faecal indicator organisms (FIOs) are major pollutants in many catchments world
wide, with streamside pastures on livestock farms being potentially significant
sources. Hitherto, few empirical studies have quantified FIO fluxes from such
areas or investigated streambank fencing (SBF) and other possible mitigation
measures. The aim of this two-phase (before/after intervention) study of the
effectiveness of SBF was to generate an empirical evidence-base to enable
regulatory authorities to make better-informed decisions concerning the
implementation of this measure. It was undertaken during the summer bathing
season along a 271 m stream reach in the River Tamar catchment, SW England. The
study included: cattle distribution surveys; monitoring of changes in E. coli
(EC) and intestinal enterococci (IE) concentrations and fluxes down the reach and
of concentrations in ditch flow and surface runoff; phage tracer studies of
surface runoff from pasture land; and experimental streambed trampling to
investigate streambed FIO sources. The results show that cattle spend a
disproportionately large amount of time in the watercourse/riparian zone along
unfenced streams; identify direct defecation to the stream by wading livestock
and the release/mobilisation of FIOs from cowpats by surface runoff from the
adjacent pastures at times of high flow as key transmission routes; and
demonstrate that FIOs become incorporated within streambed sediments, from which
they may subsequently be released by trampling. Partial exclusion of cattle
through SBF with a drinking bay greatly reduces the time cattle spend in streams.
Total exclusion SBF, with provision of an alternative drinking supply,
considerably reduces FIO load inputs to the stream reach, e.g. at times of high
flow, which are critical in terms of pollutant fluxes to coastal waters, the mean
EC and IE input loads to the reach fell by 0.842 and 2.206 log10, respectively.
PMID- 29960178
TI - Response of enhanced sludge methanogenesis by red mud to temperature:
Spectroscopic and electrochemical elucidation of endogenous redox mediators.
AB - Adding conductive materials can promote methanogenesis via facilitating electron
exchange between syntrophic bacteria and methanogenic archaea. However, little is
known about how temperature would interact with such an addition and thus affect
the compositions and characteristics of endogenous redox mediators (ERMs). In
particular, it is of strong interest to understand how the temperature variation
would affect the improvement on methanogenesis induced by ERMs with conductive
materials. Herein, we have investigated the response of sludge methanogenesis to
temperature variation (from 15 to 35 degrees C) and spectroscopically detected
the ERMs induced by conductive red mud. It was demonstrated that the increasing
temperature enhanced the stimulating effect of conductive red mud on methane
accumulation, and the methane production potential showed a linear relationship
with redox parameters such as areal capacitance (Ca), free charges (R2) and
electron exchange capacity (EEC). 2DCOS spectra further indicated that nu(C-O)
and delta(O-H) in humic acids, beta-turn type III amide I nus(C=O) in Cytochrome
c, and delta(C-H) in amines and lipids became the main redox groups in ERMs at 35
degrees C with the addition of red mud. The model revealed that the contribution
of ERMs to the CO2 reduction to CH4 increased from 35.2 +/- 1.4% to 58.6 +/- 1.5%
when the temperature increased from 15 to 35 degrees C. Our finding that
conductive materials stimulated the formation and electroactivity of ERMs with
the increasing temperature during anaerobic digestion can have important
implications for the improvement of engineered methanogenic processes.
PMID- 29960179
TI - Simultaneous removal of dissolved organic matter and nitrate from sewage
treatment plant effluents using photocatalytic membranes.
AB - The residual dissolved organic matter (DOM) and nitrate in sewage treatment plant
(STP) effluent have potential negative impacts on the aqueous environment. To
that end, we used formic acid (FA) to enhance the photochemical behavior of the
photocatalytic membrane for the simultaneous removal of DOM and nitrate from
secondary STP effluent. Effluent samples were collected from two different
biological treatment processes, Anaerobic-Oxic and Anaerobic-Anoxic-Oxic-membrane
bioreactor, respectively. Through Fourier transform-ion cyclotron resonance-mass
spectrometry (FT-ICR-MS) analysis, we found that the addition of FA resulted in a
similar molecular transformation in different STP effluent samples. Besides, the
radical signal of the carboxyl anion could be observed during the photocatalytic
process. Based on the results, we proposed the mechanism of the process that
carboxyl anion radicals generated by FA could attack DOM and result in further
oxidation of the DOM transition state to CO2 or small molecule by nitrate.
Meanwhile, CHON and CHOS compounds in DOM were attacked by the carboxyl anion
radicals more easily than CHO compounds. Moreover, long-term use of the membrane
confirmed its durability and reusability in practical applications. At a moderate
FA concentration and lower hydraulic retention time, the nitrate and DOM removal
efficiencies for the sample from JX STP were 68% and 70%, respectively, whereas
those of the CD STP sample were 85% and 60%. The removal of DOM and nitrate from
different STP effluents using photocatalytic membranes is an advanced approach
for the treatment of secondary effluent, and may be applicable to other membranes
or systems.
PMID- 29960180
TI - Cardiovascular symptoms and longitudinal declines in processing speed
differentially predict cerebral white matter lesions in older adults.
AB - It is well established that cerebral white matter lesions (WML), present in the
majority of older adults, are associated with cardiovascular and cerebrovascular
diseases and also with cognitive decline. However, much less is known about how
WML are related to other important individual characteristics and about the
generality vs. brain region-specificity of WML. In a longitudinal study of 112
community-dwelling adults (age 50-71 years at study entry), we used a machine
learning approach to evaluate the relative strength of 52 variables in
association with WML burden. Variables included socio-demographic, lifestyle, and
health indices-as well as multiple cognitive abilities (modeled as latent
constructs using factor analysis)-repeatedly measured at three- to six-year
intervals. Greater chronological age, symptoms of cardiovascular disease, and
processing speed declines were most strongly linked to elevated WML burden
(accounting for ~49% of variability in WML). Whereas frontal lobe WML burden was
associated both with elevated cardiovascular symptoms and declines in processing
speed, temporal lobe WML burden was only significantly associated with declines
in processing speed. These latter outcomes suggest that age-related WML-cognition
associations may be etiologically heterogeneous across fronto-temporal cerebral
regions.
PMID- 29960181
TI - Functional disability among partners and community activity in elderly Japanese:
The Ohsaki Cohort 2006 Study.
AB - INTRODUCTION: This cross-sectional study aimed to determine association between
partners' functional disability and community activity in an elderly Japanese
population. METHODS: A baseline survey was conducted between December 1 st and
December 15th, 2006 and included 6600 participants from whom we collected data
regarding their participation in community activity and functional disability
among their partners. We defined functional disability as receiving certification
for long-term care insurance in Japan, and frequent community activity as
engaging in community activity more than once a month. Multiple logistic
regression analysis was used to calculate odds ratios (ORs) and 95% confidence
intervals (CIs) for frequent community activity based on functional disability
among partners. We also conducted additional analyses using three types of
community activities (neighborhood associations; sports, exercise, or a hobby;
and volunteering for nonprofit organizations) as outcomes. RESULTS: Multivariate
adjusted analysis showed that the OR (95% CI) for frequent community activity was
0.70 (0.54-0.89, P < 0.01) among those whose partners had functional
disabilities, compared with those whose partners did not have functional
disabilities. This finding remained true even for different types of community
activities such as neighborhood activities, sports, exercises, hobbies, and
volunteering for nonprofit organizations. CONCLUSION: In this cross-sectional
study of an elderly Japanese population, participants whose partners had
functional disabilities were less likely to participate in community activity. We
conclude that enhancement of support systems is important to promote
participation in community activity, not only for patients with disability but
their partners as well.
PMID- 29960182
TI - Identification of jumonjiC domain containing gene family among the Oryza species
and their expression analysis in FL478, a salt tolerant rice genotype.
AB - The jumonji (JMJ)-C domain containing proteins belong to histone demethylases
family with the ability to demethylate the tri-methylated histone residues. They
act as chromatin regulators to regulate many physiological functions in plants.
The present study deals with the characterization of JMJ-C gene family members in
wild as well as cultivated rice species and their expression analysis in salt
tolerant rice genotype, FL478. The genome wide study identified 151 members
belonging to JMJ-C gene family in 11 different Oryza species. We also studied
their structure, genomic location, gene duplication events, phylogenetic
relationship, in silico expression analysis and identified cis elements in their
promoters. We also found a few JMJ-C gene family members in rice which underwent
duplication before the whole genome duplication event of the rice. The qRT-PCR
based expression profiling revealed that out of the total 15 rice JMJ-C members,
two were highly expressed in the flag leaf stage of FL478 under salt treatment.
These two candidate JMJ-C members were also found to render salinity tolerance
when over-expressed in yeast cells. Thus, the present study helps in further
structural as well as functional characterization of JMJ-C genes under salinity
stress in Oryza species.
PMID- 29960183
TI - Stomata regulation by tissue-specific expression of the Citrus sinensis MYB61
transcription factor improves water-use efficiency in Arabidopsis.
AB - Water-use efficiency (WUE) is a quantitative measurement of biomass produced per
volume of water transpired by a plant. WUE is an important physiological trait
for drought response to mitigate the water deficiency. In this work, a cisgenic
construction from Citrus sinensis was developed and its function in the
improvement of WUE was evaluated in Arabidopsis. Sequences of the CsMYB61 coding
region, a transcription factor implicated in the closure of stomata, together
with a putative stomata-specific promoter from CsMYB15, were identified and
cloned. The protein encoded in the CsMYB61 locus harbors domains and motifs
characteristic of MYB61 proteins. In addition, a 1.2 kb promoter region of the
gene CsMYB15 (pCsMYB15) containing regulatory elements for expression in guard
cells and in response to Abscisic Acid (ABA) and light was isolated. In
Arabidopsis, pCsMYB15 directs the expression of the reporter gene GUS in stomata
in the presence of light. In addition, transgenic lines expressing the CsMYB61
coding region under transcriptional control of pCsMYB15 have a normal phenotype
under in vitro and greenhouse conditions. These transgenic lines exhibited a
smaller opening of the stomata pore, lower stomatal conductance and respiration
rate, enhanced sensitivity to exogenous ABA, and high drought stress tolerance.
Our results indicate that stomata-specific expression of CsMYB61 enhances water
use efficiency under drought conditions in Arabidospis.
PMID- 29960184
TI - Residues important for K+ ion transport in the K+-dependent Na+-Ca2+ exchanger
(NCKX2).
AB - K+-dependent Na+-Ca2+ exchangers (NCKXs) play an important role in Ca2+
homeostasis in many tissues. NCKX proteins are bi-directional plasma membrane
Ca2+-transporters which utilize the inward Na+ and outward K+ gradients to move
Ca2+ ions into and out of the cytosol (4Na+:1Ca2+ + 1 K+). In this study, we
carried out scanning mutagenesis of all the residues of the highly conserved
alpha-1 and alpha-2 repeats of NCKX2 to identify residues important for K+
transport. These structural elements are thought to be critical for cation
transport. Using fluorescent intracellular Ca2+-indicating dyes, we measured the
K+ dependence of transport carried out by wildtype or mutant NCKX2 proteins
expressed in HEK293 cells and analyzed shifts in the apparent binding affinity
(Km) of mutant proteins in comparison with the wildtype exchanger. Of the 93
residue substitutions tested, 34 were found to show a significant shift in the
external K+ ion dependence of which 16 showed an increased affinity to K+ ions
and 18 showed a decreased affinity and hence are believed to be important for K+
ion binding and transport. We also identified 8 residue substitutions that
resulted in a partial loss of K+ dependence. Our biochemical data provide strong
support for the cation binding sites identified in a homology model of NCKX2
based on crystal structures reported for distantly related archaeal Na+-Ca2+
exchanger NCX_Mj. In addition, we compare our results here with our previous
studies that report on residues important for Ca2+ and Na+ binding. Supported by
CIHR MOP-81327.
PMID- 29960185
TI - Main force directions of trunk muscles: A pilot study in healthy male subjects.
AB - Muscles work most effectively along their anatomically defined action vector(s)
which has implications in training and therapeutics. Action vectors can easily be
identified in extremity muscles and smaller muscles of the trunk, but are less
clear in larger trunk muscles. Trunk muscle exercises and diagnostics have
traditionally relied on tasks in the sagittal plane - a practice that is being
reconsidered. Therefore, this study aimed at identifying main force directions
(MFDs) of major trunk muscles expressed in terms of deviation from the sagittal
plane. 20 healthy male subjects underwent graded isometric submaximal static load
applications on their trunk by application of simultaneous and incremental
tilting and rotating from vertical to horizontal at rotational angles of 45
degrees starting from 0 degrees (forward tilting) around 360 degrees with only
the lower body secured. Surface EMG (SEMG) from six trunk muscles on each body
side was recorded. The MFD of each trunk muscle was estimated by considering SEMG
amplitudes of all rotational angles, separately for all tilt angles, and was
expressed as angular deviation from sagittal plane. The calculated MFDs of trunk
muscles deviated from sagittal plane to differing extents. Mean MFD angle was
smallest (more parallel to sagittal plane) for rectus abdominis muscle (+/-14
degrees ), becoming more lateral for external oblique (OE, +/-32 degrees ) and
internal oblique abdominal muscles (OI, +/-47 degrees ). As tilt angle increased,
MFD angles increased for OE, but decreased for OI. Iliocostalis muscle showed an
almost laterally directed MFD with systematic dependency on body side (-90
degrees for left and +75 degrees for right side). Both paravertebral muscles
(longissimus and multifidus muscles) showed almost identical MFD angles of about
+/-145 degrees and varied the least with tilt angle. All trunk muscles' MFDs
deviate from sagittal plane and, in addition to flexing and extending, have both
bending and/or rotational capabilities. MFDs of oblique abdominal muscles are
systematically altered by tilt angle in accordance with their more divergent
fiber directionality. The results provide a basis for specifically targeted
diagnostics and training of trunk muscles.
PMID- 29960186
TI - Mechanisms of cellular cholesterol compartmentalization: recent insights.
AB - This review discusses advances in understanding how the controlled delivery of
cholesterol between subcellular compartments is achieved and what novel
experimental strategies are being employed to address this fundamental question.
Recent work has focused on cholesterol-binding proteins that can facilitate
directional cholesterol transfer between contacts of the ER and Golgi or late
endosomal membranes. Increasing structural information on cholesterol-binding
proteins, new modules engineered from them as well as improved imaging and gene
editing techniques are providing valuable insights. There is also mounting
information on how the crosstalk between cholesterol transport and nutrient
signaling is orchestrated and how cellular fatty acid metabolism and cholesterol
homeostasis are intertwined.
PMID- 29960187
TI - Cytotoxicity and genotoxicity of CuO nanoparticles in sea urchin spermatozoa
through oxidative stress.
AB - Copper oxide nanoparticles (CuO NPs) are extensively used in various industrial
and commercial applications. Despite their wide application may lead to the
contamination of marine ecosystem, their potential environmental effects remain
to be determined. Toxicity assessment studies have primarily focused on
investigating the effects of CuO NPs on fertilization success and embryo
development of different sea urchin species while the impact on sperm quality
have never been assessed. In this line, this study aims to assess the effects of
CuO NPs on the spermatozoa of the sea urchin Paracentrotus lividus. After sperm
exposure to CuO NPs, biomarkers of sperm viability, cytotoxicity, oxidative
stress, and genotoxicity as well as morphology were evaluated. Results showed
that CuO NPs exposure decreased sperm viability, impaired mitochondrial activity
and increased the production of reactive oxygen species (ROS) and lipid
peroxidation. Furthermore, CuO NPs exposure caused DNA damage and morphological
alterations. Together with the antioxidant rescue experiments, these results
suggest that oxidative stress is the main driver of CuO NP spermiotoxic effects.
The mechanism of toxicity is here proposed: the spontaneous generation of ROS
induced by CuO NPs and the disruption of the mitochondrial respiratory chain lead
to production of ROS that, in turn, induce lipid peroxidation and DNA damage, and
result in defective spermatozoa up to induce sperm cytotoxicity. Investigating
the effects of CuO NPs on sea urchin spermatozoa, this study provides valuable
insights into the mechanism of reproductive toxicity induced by CuO NPs.
PMID- 29960188
TI - Safety of pitch-side care provision in community contact sport within England.
PMID- 29960189
TI - Mowing: A cause of invasion, but also a potential solution for management of the
invasive, alien plant species Erigeron annuus (L.) Pers.
AB - Erigeron annuus is one of the major invasive, alien plants in Korea, and
therefore research to manage (control) this invasive plant is essential. In this
research, studies were conducted to determine the mechanisms by which E. annuus
became the dominant plant at a landfill site and to develop management strategies
for this alien plant. Because the seeds and seedling stage did not have superior
adaptations to disturbed soil, demonstrate allelopathy, outcompete other species,
or show rapid growth, the disturbance from mowing was likely the primary reason
for the dominance of E. annuus. The areas without mowing showed a significant
decrease in the coverage of E. annuus, whereas the mowed (managed) areas showed a
significant increase. Additionally, mowing once increased the weight of
reproductive organs by 50% and suppressed the growth of native species. Thus, the
primary factor in the invasion of the alien species E. annuus was mowing, and, to
control such an invasion, areas should be protected from mowing. Additionally,
with selective mowing that targeted only E. annuus, mowing three times produced
only approximately 10% of the reproductive organ biomass compared with that of
the control. Because the flower stalk of E. annuus was relatively tall compared
with that of native species in early summer, selective mowing might also provide
a solution to control invasions of E. annuus. Therefore, with improved ecological
understanding of the site and species, mowing of the right target during the
optimal season and at an appropriate frequency is an environmental friendly
solution to the management of E. annuus.
PMID- 29960190
TI - Revisiting the temperature-economic growth relationship using global subnational
data.
AB - Previous studies have used national data to demonstrate that higher annual
temperatures negatively affect economic output and growth. Yet, annual
temperatures and productivity can also vary greatly across space within
countries. With this in mind, we revisit the relationship between temperature and
economic growth using subnational short panel data for 10,597 grid cells across
the terrestrial Earth. Our estimates from fitting a quadratic model to the data
imply that cell-level economic growth in countries with below-median per-capita
incomes is concave in temperature, with a maximum at about 16 degrees C. Our
findings suggest that even with similar economic development within a country,
climate vulnerability can vary at the regional level. Furthermore, as soon as we
take into account the nonlinear relationship between temperatures and economic
growth within countries, the impacts of temperature increases are found to be
larger, compared to those that disregard such within-country heterogeneity.
PMID- 29960192
TI - Biochar from sewage sludge and pruning trees reduced porewater Cd, Pb and Zn
concentrations in acidic, but not basic, mine soils under hydric conditions.
AB - This study aimed to assess the effectiveness of biochar from sewage sludge -BSS-
and from pruning trees -BPT- (addition dose of 6% d.w.) to immobilise metals in
acidic (pH ~ 4.7) and basic (pH ~ 7.4) mine soils under variable flooding
conditions, and to determine biochar influence on plant (Sarcocornia fruticosa
Sf-) growth and metal uptake. BSS had lower pH (~8.2 vs. ~ 9.8), CaCO3 (~71 vs. ~
85 g kg-1), total organic carbon (~354 vs. ~ 656 g kg-1) and higher water soluble
organic carbon (WSOC ~ 0.15 vs ~ 0.06 mg kg-1) than BPT. PVC columns (15 * 30 cm)
were prepared with the following treatments (n = 4): 1) no Biochar-no Sf; 2) no
Biochar-Sf; 3) BSS-no Sf; 4) BSS-Sf; 5) BPT-no Sf; 6) BPT-Sf. Changes in water
table level (WL) were simulated for 303 days with tap water (upper 0-15 cm
alternating flooding-drying conditions, lower 15-30 cm always underwater). The
pH, redox potential (Eh), temperature and porewater WSOC, Zn, Cd and Pb
concentrations were regularly measured, and plants were removed at the end and
length, fresh weight and metal concentrations in tissues measured. In the basic
soil, there were no consistent evidences that BSS and BPT were effective
decreasing porewater metal concentrations and reducing metal uptake in plants. Sf
contributed to mobilise Zn, and in less extent Cd, in the upper soil layer,
regardless of the type of biochar, and this effect increased with aging. In the
acidic soil, BSS and BPT were effective increasing the pH and decreasing
porewater metals. BSS increased its efficiency with aging, which can be mainly
attributable to the more reduced conditions that induced (lower Eh values) due to
its higher WSOC content. Biochar was effective hindering metal mobilisation by Sf
and reducing plant's metal uptake (e.g. reduction in roots: ~7 fold for Zn, ~19
fold for Cd and ~ 2-fold for Pb). BSS was more effective promoting Sf growth
(fresh weight) than BPT. Therefore, in relation with the use of biochar from
sewage sludge and from pruning trees as soil amendments under flooding-non
flooding conditions, we can conclude that it can be a useful option in acidic
mine soils for decreasing water soluble metals and improving plant growth.
However, in basic mine soils, we have no evidences to support the advantages of
using these two types of biochar as amendments. Hence, the use of biochar in
metal-polluted wetlands has environmental implications that must be planned for
each specific case in order to optimize the positive aspects (wetland as sinks of
pollutants) and reduce the drawbacks (wetland as source of pollutants).
PMID- 29960191
TI - Behaviour of doxycycline, oxytetracycline, tetracycline and flumequine during
manure up-cycling for fertilizer production.
AB - The fate of four widely used veterinary antibiotics (doxycycline, flumequine,
oxytetracycline and tetracycline) during manure upcycling was investigated at
laboratory and pilot scale. The pilot was operated continuously, while the
laboratory scale in batch mode. Both set-ups consisted of anaerobic digestion,
ammonia stripping and a solid liquid separation step. A partial nitritation
anammox process was used to treat the laboratory scale effluent. In the pilot
installation, pig manure as feed, natural occurring antibiotics levels were
reduced by 92% for doxycycline, 88% for flumequine, 95% for oxytetracycline and
100% for tetracycline. In the laboratory scale set-up, antibiotic free sludge was
used and the four substances were spiked. The input antibiotics concentration was
reduced by 85% for doxycycline, 46% for flumequine, 97% for oxytetracycline and
100% for tetracycline. In both set-ups the centrifuge cake was identified as the
major emission pathway for residual antibiotics. Manure upcycling, while
producing fertilizers, can be considered effective in reducing the residual
antibiotic load.
PMID- 29960193
TI - Prolonged therapy with antidepressants increases hippocampal level of kynurenic
acid and expression of Kat1 and Kat2 genes.
AB - BACKGROUND: Accumulating data suggest an important role of disturbed kynurenine
pathway and altered glutamatergic transmission in the pathogenesis of depression.
In here, we focused on detailed analyses of kynurenic acid (KYNA) status in vivo
following single and 14-day administration of selected tricyclic antidepressant
drugs (TCAs) and serotonin selective reuptake inhibitors (SSRIs) in rats.
METHODS: The effect of antidepressants on serum and brain KYNA levels, as well as
on the activity of kynurenine aminotransferases (KATs I and II) and expression of
Kat1 and Kat2 genes mRNA was studied in three brain regions. RESULTS: Chronic,
but not acute, application of antidepressants invariably stimulated KYNA
production in hippocampus (amitriptyline, imipramine, fluoxetine and citalopram)
and sporadically in cortex (amitriptyline, fluoxetine), whereas no change in KYNA
level was observed in striatum. Cortical and hippocampal expression of Kat1 and
Kat2 genes was increased after chronic, but not single administration of all
studied antidepressants. The activity of semi-purified enzymatic proteins, KAT I
and II, was not paralleling changes of Kat1 and Kat2 genes. CONCLUSION: Our data
indicate that prolonged administration of antidepressants targets expression of
KYNA biosynthetic enzymes. Furthermore, post-translational modulation of KATs
seems to play an important role in tuning of KYNA synthesis within brain
structures. We suggest that consistent increase of hippocampal KYNA levels may
represent hallmark of antidepressant activity. Mechanisms governing region- and
drug-selective action of antidepressants require further investigations.
PMID- 29960194
TI - Adult dragonflies are indicators of environmental metallic elements.
AB - Adult dragonflies (Insecta; Odonata) are aerial predatory arthropods that occur
globally except in the polar regions. However, we know of no research on adult
dragonflies as potential indicators of metallic elements in the environment or
metallic element concentrations and relative contribution patterns between sites,
species, size classes, habitat types, and relation to possible pollution sources.
There is also no information available about adult dragonflies and their
responses to toxic metals. However, metallic elements are toxic in elevated
concentrations to all organisms. We predict that adult dragonflies would be
suitable indicators of elemental concentrations. We analysed 105 adult male
dragonflies from 21 sites in South Africa for 33 metallic elements including Hg,
As, Pb, Cr, Cu, Cd, Ni, Se, Al, and Au. The results indicated that all species of
dragonflies, regardless of body size, are suitable indicators. Furthermore,
different aquatic habitat types did not affect the metallic element
concentrations at the scale of this study. Dragonflies collected near wastewater
treatment plants showed concentrations of certain elements such as Au higher than
from elsewhere. Elements such as As and Pb were found at elevated concentrations
(relative to the other sites) in dragonflies collected near mines. Dragonflies
from sampling sites near potential pollution sources, but had seemingly isolated
water sources, showed lower metallic element concentrations when compared with
other sites. We conclude that adult dragonflies would be good indicators of
environmental metallic elements.
PMID- 29960195
TI - Soil mutagenicity - Effects of acidification and organic pollutants in
urban/industrial areas.
AB - This study aimed to analyze (i) the effect of different acid extractions,
simulating changes in the background pH of rain on the availability of soil
mutagenic compounds, (ii) the presence of organic compounds in soil and (iii)
evaluation of the effects of soil sieving on the samples mutagenicity. Surface
soil samples were collected at urban and industrial areas and assessed as total
grain size composition (Total Soil) and in sieved fraction <0.5 mm (Soil <0.5
mm), through acid extracts with pH simulating those found in local rainfall.
Metals were quantified in extracts and soils in natura. Organic extracts were
analyzed for PAH content. Salmonella/microsome mutagenicity assay (TA98 strain)
was used, in the presence/absence of exogenous metabolism. Nitro-sensitive
strains YG1021 and YG1024 were used in the organic extracts. Results showed
different mutagenic responses in total soils and in soil <0.5 mm. Soil extraction
at pH 3.6 presented higher toxicity, greater variety and concentration of metals.
Extraction at pH 5.3 improved mutagenic detection. Thus, local rainfall may be an
environmental contamination route, with additional risk of releasing toxic
substances during acid precipitation events.
PMID- 29960197
TI - The international symposium BFR2017, York, UK.
PMID- 29960196
TI - Emerging contaminants in Brazilian rivers: Occurrence and effects on gene
expression in zebrafish (Danio rerio) embryos.
AB - Emerging contaminants (ECs) are synthetic or naturally occurring chemicals that
are not commonly monitored despite having the potential of entering the
environment and causing adverse ecological and/or human health effects. This
study aimed to determine whether ECs are present in the surface waters of two
rivers in Mato Grosso do Sul State, Brazil, and evaluate the effects of ECs
mixtures at environmentally relevant concentrations on zebrafish (Danio rerio)
gene expression. ECs concentrations were determined using solid-phase extraction
and liquid chromatography-mass spectrometry. The ECs most frequently detected
were caffeine, imidacloprid, 2-hydroxy atrazine, tebuthiuron, atrazine, and
bisphenol A. We used these data to reconstruct ECs mixtures reflecting
environmental concentrations, codenamed T1, T2, and T3. No effects were observed,
so the concentrations were increased. After a preliminary evaluation of the No
Observed Effect Concentration for each mixture, we analyzed changes in the
expression of zebrafish target genes (cyp1a, hsp70, cat, sod1, tsh, cyp19a1a,
cyp19a1b, cyp26b1, casp8, sox2, cyb561d2, and thrb). cat was overrepresented in
T1 and underrepresented in the other treatments. All of the mixtures induced the
expression of cyp19a1b, which is a marker for (xeno-)estrogen exposure, and two
of them increased the expression of cyp1a, which is used to indicate the presence
of dioxin-like compounds. The rivers studied had low EC concentrations, and there
was no indication of any harmful effects on the zebrafish. However, intensive
agricultural activity may result in unsuspected peaks of EC pollution, and
subsequent negative effects on living organisms.
PMID- 29960198
TI - Solvent-based separation and recycling of waste plastics: A review.
AB - Since the creation of first man-made plastic, the global production and
consumption of plastics have been continuously increasing. However, because
plastic materials are durable and very slow to degrade, they become waste with
high staying power. The over-consumption, disposal, and littering of plastics
result in pollution, thus causing serious environmental consequences. To date,
only a fraction of waste plastics is reused and recycled. In fact, recycling
plastics remains a great challenge because of technical challenges and relatively
insufficient profits, especially in mixed plastics. This review focuses on an
environmentally friendly and potentially profitable method for plastics
separation and recovery and solvents extraction. It includes the
dissolution/reprecipitation method and supercritical fluid extraction, which
produce high-quality recovered plastics comparable to virgin materials. These
methods are summarized and discussed taking mass-produced plastics (PS, PC,
Polyolefins, PET, ABS, and PVC) as examples. To exploit the method, the quality
and efficiency of solvent extraction are elaborated. By eliminating these
technical challenges, the solvent extraction method is becoming more promising
and sustainable for plastic issues and polymer markets.
PMID- 29960199
TI - A recyclable adsorbent for salinized groundwater: Dual-adsorbent desalination and
potassium-exchanged zeolite production.
AB - This study focused on advancing the dual-adsorbent desalination technique that
sequentially combines calcined layered double hydroxide (CLDH) and acid-treated
zeolites (H-form zeolite) using groundwater spiked with potash mining effluent
(brine). In sequential batch experiments, the CLDH adsorbent first reduced the
high Cl- concentration (4600 mg/L) of saline groundwater by 96%, the Ca2+ by 90%,
and the Mg2+ by 92%, while transiently raising the pH to 12.80. H-form zeolites
preconditioned with Na+ then removed 92% of the Na+ (2010 mg/L), while
neutralizing the adsorption effluent pH to 7.7 and lowering the sodium adsorption
ratio (SAR; 139.6 to 6.6) and the hardness (574 to 48.4 mg/L). In comparison, an
equivalent amount of unmodified zeolite removed only 51% of the Na+ and generated
extremely hard water due to Ca2+ and Mg2+ release (1519 mg/L). Na+-conditioning
the zeolites prior to acid treatment enhances native cation removal, forming H
form zeolites. Synchrotron-based X-ray scanning transmission microscopy (STXM)
showed the occurrence of dealumination and visualized the sodium distribution
associated with Si and Al sites in the H-form zeolites. Four consecutive
desalination cycles were feasible for Na+ and K+ adsorption by regenerating the H
form zeolite. During regeneration, the Na+ desorbed while the K+ remained in the
regenerated zeolites. Cumulative K+ loading in the regenerated zeolites increased
from 4.8 to 21.2 mg/g, producing K-form zeolites. These K-form zeolites released
K+ (2.15 mg/L for 24 h) in a leaching test and could potentially be considered as
nutrient-supply media in other applications, thereby recycling the spent zeolites
after multiple desalination treatments.
PMID- 29960200
TI - Vaginal diazepam plus transcutaneous electrical nerve stimulation to treat
vestibulodynia: A randomized controlled trial.
AB - OBJECTIVE: To assess the effectiveness of vaginal diazepam in addition to
transcutaneous electrical nerve stimulation (TENS) in the treatment of
vestibulodynia (VBD). STUDY DESIGN: This study was a randomized, double-blind,
placebo-controlled trial. Forty-two patients with VBD were randomized, 21
underwent diazepam and TENS (diazepam group) and 21 received placebo and TENS
(placebo group). Vulvar pain was assessed on a on a 10-cm visual analogue scale
(VAS) and dyspareunia according to the Marinoff dyspareunia scale. Vaginal
surface electromyography (EMG) and vestibular current perception threshold (CPT)
testing were performed at baseline and 60 days after treatment. The primary
endpoints included the change in pain and dyspareunia from baseline to 60 days of
pain and dyspareunia. The secondary endpoints was the variation in objectivity of
pelvic floor muscle (PFM) function and vestibular nerve fiber current perception
threshold (CPT). RESULTS: The VAS scores for pain from basal values of 7.5 and
7.2 for the diazepam and placebo, respectively, showed significant (p 0.01)
decreases from 4.7 to 4.3, but this difference was not statistically significant.
The Marinoff dyspareunia scores in the diazepam group showed a significant
difference (p 0.05) from values measured in the placebo group. The ability to
relax the PFM after contraction (difference between maximal contraction and rest
tone) was significantly greater for the diazepam group versus the placebo group
(3.8 MUv and 2.4 MUv, respectively, p 0.01). The CPT values for all of the nerve
fibers increased after the treatment, but this increase was significant in the
diazepam group only for the values at a 5-Hz stimulation (C fibers) with a change
of 47.8% vs 26.9% (p < 0.05). Only two patients reported a mild drowsiness in the
diazepam group. CONCLUSIONS: The present study provided indications that vaginal
diazepam plus TENS is useful to improve pain and PFM instability in women with
VBD.
PMID- 29960201
TI - A study of treatments and outcomes in elderly women with cervical cancer.
AB - OBJECTIVE: With the population aging, development of safe and effective
treatments for elderly patients with cancer is needed. Although old age is
considered a poor prognostic factor, this is not only because of the patient's
disease condition or response to treatment, but also because of treatment
strategy and intensity. The purpose of this study was to clarify the influence of
age on treatment and prognosis in patients with cervical cancer. METHODS: Women
with stage Ib-IV cervical cancer treated at our institution between 1997 and 2014
were retrospectively analyzed. Patients were stratified by age into groups for
analysis, <65 years and >=65 years. Categorical variables were compared using chi
squared and Fisher's exact tests. Survival analyses were performed using the
Kaplan-Meier method, and comparisons were made using the log-rank test.
Subsequently, Cox proportional hazards models were developed to find independent
prognostic factors. RESULTS: Of 959 patients included in our study, 247 were >=65
and 712 were <65 years of age. Elderly patients tended to be at a more advanced
stage than younger patients (p < 0.001). Elderly patients more commonly had
comorbidities. More received standard treatment in the younger patient group at
any disease stage than in the elderly patient group (p < 0.001). Similar rates of
adverse effects caused by surgery or radiotherapy were seen in patients from both
groups. Although overall survival was statistically shorter in elderly patients
(74.7 vs. 57.1%, p < 0.001), there was no significant difference in disease
specific survival for patients treated only with standard treatment. In
multivariate analyses, clinical stage, histological type, treatment intensity,
and primary surgery remained independent prognostic factors. Age was not an
independent prognostic factor. CONCLUSIONS: The influence of age on prognosis in
patients with cervical cancer was less than we expected. Elderly patients might
have better outcomes depending on the type of standard treatment they receive.
The appropriate modality and intensity of treatment should be based on the
patient's general condition and background.
PMID- 29960202
TI - Characterizing peer roles in an overdose crisis: Preferences for peer workers in
overdose response programs in emergency shelters.
AB - OBJECTIVES: A growing body of research points to increasing peer involvement in
programs for people who use drugs, although this work has focused primarily on
naloxone education and distribution. This study extends this work by examining
the roles of peers in leading a novel overdose response program within emergency
shelters. METHODS: Semi-structured qualitative interviews were conducted with 24
people who use drugs, recruited from two emergency shelters, as well as
ethnographic observation in these settings. Interviews were transcribed and
analyzed thematically with attention to peer roles. RESULTS: Four themes emerged
from the data. First, participants discussed the development of peer support
through relationship building and trust. Second, participants described a level
of safety using drugs in front of peer workers due to their shared lived
experience. Third, peer workers were described as favorable compared to non-peer
staff because of nominal power dynamics and past negative experiences with non
peer staff. Last, given the context of the overdose crisis, peer worker roles
were often routinized informally across the social networks of residents, which
fostered a collective obligation to respond to overdoses. CONCLUSIONS: Findings
indicate that participants regarded peer workers as providing a range of unique
benefits. They emphasized the critical role of both social networks and informal
roles in optimizing overdose responses. The scaling up of peer programming in
distinct risk environments such as emergency shelters through both formal and
informal roles has potential to help improve overdose prevention efforts,
including in settings not well served by conventional public health programming.
PMID- 29960203
TI - Correlates of suicide ideation and behaviors among transgender people: A
systematic review guided by ideation-to-action theory.
AB - Transgender people are at high risk for suicide ideation, attempts, and deaths
compared to the general population. Several correlates of suicide ideation and
attempts have been identified empirically to understand this increased risk.
However, few attempts have been made to systematically review this literature.
Further, a theory to understand and identify targetable factors for intervention
has rarely been applied to this population. In the first systematic review guided
by ideation-to-action frameworks of suicide, we systematically reviewed the
literature from January 1991 to July 2017 regarding correlates of suicide
ideation, attempts, and deaths among transgender people. To be included in the
review, articles must have been reported in English, reported on empirical data,
included a sample or subsample of transgender people, and reported separately on
correlates of suicide ideation, attempts, or deaths. Two independent reviewers
searched three major databases, references of included articles, and unpublished
literature, which produced 45 articles for review. The review suggested that
ideation-to-action frameworks would be worth investigating within this
population, with attention to sources of psychological pain, social
connectedness, and capacity/capability for suicide unique to this population.
Additionally, other aspects of cultural identity were often studied (e.g., race,
religion), suggesting the need to understand intersectionality of identities
among transgender people and their effects on suicide risk. Finally, the review
highlighted important limitations of the literature, namely measurement of
suicide ideation and attempts and sampling method, which future work should seek
to improve.
PMID- 29960204
TI - Prescription drug use, misuse and related substance use disorder symptoms vary by
educational status and attainment in U.S. adolescents and young adults.
AB - BACKGROUND: Prescription drug misuse (PDM) rates are highest in adolescents and
young adults. Little research in these high-risk groups has examined PDM
differences by educational status or attainment. This investigation attempted to
further our understanding of adolescent and young adult prescription drug use and
misuse through examining PDM type (i.e., nonmedical misuse, medical misuse and
mixed misuse) and substance use disorder (SUD) symptoms from PDM by educational
status/attainment. METHODS: Data were from the 2015 National Survey on Drug Use
and Health, with 13,585 adolescent and 14,553 young adult respondents.
Participants were categorized by educational status separately in adolescents and
young adults. Outcomes were rates of past-year prescription drug use, PDM, PDM
type, and SUD symptoms, with analyses performed separately by age group and for
opioids, stimulants and sedatives/tranquilizers. Analyses used logistic
regression and controlled for age, race/ethnicity and sex. RESULTS: In
adolescents and across medication classes, the highest rates of any use, PDM,
medical misuse, nonmedical misuse and presence of two or more SUD symptoms were
seen in those with poor school adjustment or not in school. In young adults,
opioid-PDM and related outcomes were more prevalent in those not in school,
especially high school dropouts. For stimulants, rates were highest in full-time
college students and college graduates. CONCLUSIONS: These results further
suggest the importance of assessing educational status in adolescent and
educational attainment in young adult PDM investigations. Adolescents poorly
engaged in school or not in school appear especially in need of interventions to
limit PDM and associated SUD symptoms.
PMID- 29960205
TI - Cefiderocol (S-649266), A new siderophore cephalosporin exhibiting potent
activities against Pseudomonas aeruginosa and other gram-negative pathogens
including multi-drug resistant bacteria: Structure activity relationship.
AB - The structure-activity relationship (SAR) for a novel series of catechol
conjugated siderophore cephalosporins is described with their in vitro activities
against multi-drug resistant Gram-negative pathogens including Pseudomonas
aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and
Enterobacteriaceae. Cefiderocol (3) was one of the best molecules which displayed
well-balanced and potent activities against multi-drug resistant Gram-negative
pathogens including carbapenem resistant bacteria among the prepared compounds
with the modified C-7 side chain and the modified C-3 side chain. Cefiderocol (3)
is a highly promising parenteral cephalosporin for the treatment of multi-drug
resistant Gram-negative infection.
PMID- 29960206
TI - Homopiperazine-rhodamine B adducts of triterpenoic acids are strong mitocans.
AB - Parent pentacyclic triterpenoic acids such as ursolic-, oleanolic,
glycyrrhetinic, betulinic and boswellic acid were converted into their acetylated
piperazinyl amides that were coupled with rhodamine B. SRB assays to evaluate
their cytotoxicity showed all of these triterpene-homopiperazinyl-rhodamine
adducts 16-20 being highly cytotoxic for a panel of human tumor cell lines even
in nanomolar concentrations while being significantly less cytotoxic for non
malignant cells. Interestingly enough, these compounds were even more cytotoxic
than previously prepared piperazinyl analogs, thus making the homopiperazinyl
spacer a very interesting scaffold for the development of biologically active
compounds. Extra staining experiments showed that the cytostatic effect of
compounds 18 and 20 onto A2780 cancer cells is due to their ability to act as a
mitocan.
PMID- 29960207
TI - Targeting prohibitin with small molecules to promote melanogenesis and apoptosis
in melanoma cells.
AB - Prohibitins 1 and 2 (PHB1/2) are scaffold proteins that are involved in both
melanogenesis and oncogenic pathways. We hypothesized that a PHB1 ligand,
melanogenin, may display anti-cancer effects in addition to its known melanogenic
activity in melanocytes. Here, we disclose a convenient synthesis of melanogenin,
and its analogs. We found that, among 57 new melanogenin analogs, two (Mel9 and
Mel41) significantly promoted both melanogenesis in melanocytes by activating one
of the PHB2-interacting proteins, microtubule-associated protein light chain 3
(LC3), and upregulating the expression of microphthalmia associated transcription
factor (MITF). These analogs also activate ERK. Besides, in addition to their
promelanogenic activities, we uncovered that melanogenin and its active analogs
induce apoptosis in several cancer cell lines, including melanoma cells, and that
this effect is caused by an inhibition of AKT survival pathway. Our findings
present a new putative function for PHBs as regulators of LC3/ERK/MITF
melanogenic signaling, and suggest that Mel9 and Mel41 may provide the basis for
the development of new drugs candidates to treat melanoma and other types of
cancers.
PMID- 29960208
TI - A case report of an incidental Brenner tumor found after resection of a large
ovarian mucinous neoplasm.
AB - INTRODUCTION: Brenner Tumors are rare adenofibromas that are most commonly benign
and discovered in post-menopausal women. PRESENTATION OF CASE: This is a case
report of a 57-year-old female with three months of progressively worsening
abdominal pain due to a large abdominal mass discovered on CT scan. Surgical
removal of the mass revealed a giant mucinous tumor of the ovary with an
associated Brenner tumor that was discovered incidentally. DISCUSSION: Although
the Brenner tumor was accurately identified in the intraoperative frozen section
evaluation, the mucinous tumor was underdiagnosed by frozen section as benign
when permanent section revealed borderline mucinous cystadenoma. This finding did
not change the treatment course for this particular patient as she had expressed
personal preference for total abdominal hysterectomy. However, underdiagnosis of
frozen sections of ovarian tumors is not rare. It is unclear whether an
associated Brenner tumor increases malignancy potential. CONCLUSION: Further
investigation is required to determine whether associated Brenner tumors found
during frozen section are more highly associated with malignancy and could
therefore change intraoperative and overall decision making.
PMID- 29960209
TI - Gall stone ileus: Unfamiliar cause of bowel obstruction. Case report and
literature review.
AB - INTRODUCTION: Gallstone ileus is a rare sequela of cholelithiasis. The pathology
occurs as a result of bilioenteric fistula due to erosion by the offending
gallbladder stone. It is most commonly encountered in elderly females and CT
imaging is diagnostic in the majority of cases. Surgical intervention aims to
promptly relief the obstruction by removing the gallstone and dealing with the
fistula. Morbidity and mortality are usually high since it usually occurs in
elderly patients. PRESENTATION OF CASE: An 88-year-old lady with multiple chronic
medical problems and no history of biliary manifestation presented with acute
small bowel obstruction. Abdominal CT imaging revealed a bilioenteric fistula and
an impacted gallstone in the jejunum causing occlusion. Laparotomy was performed
and the stone was removed via enterolithotomy. Manipulation of the
cholecystoduodenal fistula was not attempted due to severe inflammatory
adhesions. The patient had uneventiful postoperative course and remained symptom
free on one year follow-up. DISCUSSION AND CONCLUSION: Management of gallstone
ileus is mainly surgical. Delay in detection and treatment of gallstone ileus may
result in significant morbidity and mortality. The choice of surgical option is
influenced by the preoperative medical status of the patient. A literature review
generally supports the employment of enterolithotomy in high-risk patients and
reserving cholecystectomy and resection of the fistula for less comorbid patients
with feasible anatomy.
PMID- 29960210
TI - A case of De Garengeot's hernia with acute appendicitis and literature review.
AB - BACKGROUND: De Garengeot hernia is defined as femoral hernia containing appendix.
An acute appendicitis in a femoral hernia is a extremely unusual surgical finding
and occurs in 0.08%-0.013% of all cases. CASE REPORT: We report the case of an
elderly woman, who presented with a typical clinical image of incarcerated
femoral hernia and underwent open surgery. An infrainguinal incision was
performed and after the dissection of hernia sac, an acute appendicitis within
femoral hernia was revealed. Subsequently, appendectomy and hernioplasty were
performed. CONCLUSION: Acute appendicitis within femoral hernia should be
included in differential diagnosis of patients presenting with clinical signs of
an incarcerated femoral hernia and prompt surgical treatment is essential in
order to avoid severe complications.
PMID- 29960212
TI - Correspondence of maternal and paternal perception of school-aged children's
sleep with in-home sleep-electroencephalography and diary-reports of children's
sleep.
AB - OBJECTIVE: Parents are often the first to report children's sleep difficulties.
The aim of the present study was to evaluate the accuracy of parent reports by
examining the correspondence of maternal and paternal reports of children's sleep
with in-home electroencephalography (EEG) sleep assessment and sleep diary
reports. METHODS: A total of 143 children (57 formerly very preterm born
children) aged 7-12 years underwent one night of in-home sleep-EEG; mothers and
fathers reported children's sleep-related behavior by using the German version of
the Children's Sleep Habits Questionnaire, and children and parents together
completed a sleep diary of children's sleep. RESULTS: Less EEG-derived total
sleep time (TST) was associated with increased mother questionnaire reports of
sleep duration problems, while less sleep efficiency (SE) and longer sleep onset
latency (SOL) were associated with increased mother questionnaire reports of
sleep onset delay. For fathers, only longer SOL was related to increased father
questionnaire reports of sleep onset delay. The abovementioned associations did
not change with children's increasing age and did not differ for boys and girls.
More parent questionnaire reports of sleep duration problems, sleep onset delay,
and night wakings were related to shorter diary reports of sleep duration,
increased sleep latency, and more nocturnal awakenings, respectively.
CONCLUSIONS: Mother questionnaire reports of children's sleep corresponded
moderately with objective measures of TST, SE, and SOL assessed with in-home
sleep-EEG. Both mother and father questionnaire reports of children's sleep
duration problems, sleep onset delay, and night wakings were related to diary
reports of children's sleep.
PMID- 29960211
TI - "Sleep disordered breathing and ECG R-wave to radial artery pulse delay, The
Multi-Ethnic Study of Atherosclerosis".
AB - BACKGROUND: Electrocardiography R-wave to radial artery pulse delay (RRD)
represents pulse transit time inclusive of pre-ejection period (PEP) and arterial
pulse propagation time. RRD is proposed to largely reflect arterial stiffness
when PEP is accounted for (shorter RRD = higher arterial stiffness). Sleep
disordered breathing (SDB) causes intermittent hypoxemia and sympathetic
activation, which negatively influences vascular function. We aimed to examine
the association of measures of SDB with RRD. METHODS: Our sample consisted of
participants in the Multi-Ethnic Study of Atherosclerosis without prevalent
cardiovascular disease who underwent a daytime arterial elasticity exam, cardiac
magnetic resonance imaging (MRI), and overnight polysomnography. SDB measures of
interest included apnea hypopnea index (AHI) and oxygen desaturation index (ODI)
(N = 1173). RRD was regressed on each measure of SDB separately, with adjustment
for other cardiovascular risk factors as well as for correlates of the PEP,
another component of RRD, by including cardiac MRI measures of contractility and
preload. RESULTS: In multivariate analysis, among measures of SDB, ODI, a marker
of intermittent hypoxemia, was inversely associated with RRD (beta = -60.2 msec
per SD [15.5/hr], p = 0.04). No significant association was found with AHI. In
gender stratified analyses, ODI and AHI were predictive of RRD in men only (beta
= -111.3 msec per SD [15.5/hr], p = 0.01 and beta = -100.3 msec per SD [16.1/hr],
p = 0.02 respectively). CONCLUSION: Severity of SDB as measured by ODI was
associated with RRD, a marker of arterial stiffness. Thus, association of RRD
with measures of SDB appears to be gender-dependent.
PMID- 29960213
TI - Overweight and obese children with sleep disordered breathing have elevated
arterial stiffness.
AB - BACKGROUND: The prevalence of obese children with sleep disordered breathing
(SDB) is increasing. Obesity and SDB are independent cardiovascular risk factors,
of which arterial stiffness is an early sign. Pulse wave velocity (PWV), is a
marker of arterial stiffness and central systolic blood pressure (cSBP) is a
better predictor of cardiovascular outcome than peripheral blood pressure.
Therefore, we aimed to determine PWV and cSBP in overweight/obese or normal
weight children with sleep disordered breathing (SDB), and non-snoring normal
weight controls. METHODS: Children (3-18 y) with SDB (overweight/obese [BMI z
scores >= 1.04], n = 48; normal weight n = 44) referred for clinical assessment
of SDB and normal weight non-snoring controls recruited from the community (n =
38) underwent overnight polysomnography. PWV was calculated using
photoplethysmography. cSBP was calculated using applanation tonometry in a subset
of children older than 8 y (n = 55) who had usable waveforms. RESULTS:
Overweight/obese SDB group had higher PWV (mean cm/s (95% CI); wake: 366 (355
380); sleep: 340 (324-357)), than the normal-weight SDB group (wake: 257 (247
267), p = 0.002; sleep: 255 (242-269), p = 0.005), and non-snoring controls
(wake: 238 (226-249), p = 0.002; sleep: 235 (220-250), p < 0.001). The normal
weight SDB group had higher PWV than controls (p = 0.03). Overweight/obese
children with SDB had higher cSBP (105 (100-110) mmHg) compared with the normal
weight children with SDB (96 (90-102)) and the non-snoring controls (97 (91-104);
p < 0.05 for both). CONCLUSION: This study suggests that overweight/obesity
substantially worsens the cardiovascular sequelae of SDB, highlighting the
imperative to treat obesity and SDB in children early in order to reduce future
cardiovascular disease risk.
PMID- 29960214
TI - Activity enhancement of selective antitumoral selenodiazoles formulated with
poloxamine micelles.
AB - Selenium (Se) incorporated into organic frameworks has demonstrated anticancer
activity against several cancer types. One of the drawbacks of most of these
constructs is their poor solubility and bioavailability, which can be overcome
with the use of suitable nanocarriers. We have synthesized a series of 5
substituted amide selenodiazoles, based on the parent structure of ebselen, an
organoselenium drug with proven cytoprotective activity, and solubilized them in
polymeric micelles of poloxamines, poly(ethylene oxide)-poly(propylene oxide) X
shaped tetrablock-copolymers. Scattering methods (SANS and DLS) were employed to
characterize the micellar nanocarriers. MTT biological evaluation highlights the
selectivity of the Se-compounds towards cancer cells, with MCF-7 standing as the
most responsive line. The alkylation of the heterocycle with a 12-carbon
hydrophobic tail displays the highest activity, showing a 100-fold increase with
respect to ebselen. This compound also exhibits the greatest increase in
solubility in poloxamine micelles, overall resulting in a one-fold increase in
activity with respect to the non-formulated form, making it a hit compound for
further optimization.
PMID- 29960215
TI - Selective contrast agents with potential to the earlier detection of tumors:
Insights on synthetic pathways, physicochemical properties and performance in MRI
assays.
AB - Magnetic iron oxide nanoparticles (MNPs) have been prepared and stabilized with
three organic acids (tartaric, malic and ascorbic) in order to obtain
biocompatible and water dispersible MNPs with potential to bind specifically to
tumoral cancer cells. An in deep characterization was performed aiming to verify
the presence and effect of the coating and stabilizer on MNPs surface. Besides
the mechanisms followed by the different acids to bind MNPs were elucidated and
used to justify the differences in the physicochemical properties of each
formulation. Data related to characterization revealed that MNPs coated with
ascorbic acid (MNPs-AA) resulted the most suitable in terms of their size,
surface charge and stability along the time. Besides, ascorbic acid may be
recognized by GLUTs receptors that are overexpressed in several kinds of tumoral
cells. Therefore, MNPs-AA was selected to explore its performance in both MRI and
in vitro assays using human colon cancer cells HCT 116. MRI experiments were
performed in clinical equipment using a series of aqueous dispersions of MNPs-AA
that were evaluated as T2 contrast agent. The T2- weighted images obtained as
well as the calculated r2, indicated that MNPs-AA could act as efficient T2
contrast agent for MRI. Regarding in vitro assays, MNPs-AA did not alter the
cellular function neither exert cytotoxicity using the three explored doses. The
internalization of the nanoparticles on the cellular structure was confirmed
quanti and qualitatively using atomic absorption spectroscopy and Prussian blue
techniques respectively. From these results, it emerges that ascorbic acid coated
magnetite nanoparticles may be used as alternative contrast agent to avoid or
minimize some toxicological issues related to the widely used gadolinium.
PMID- 29960217
TI - Brand name to generic substitution of levetiracetam in patients with epilepsy.
AB - PURPOSE: Levetiracetam is one of the most widely used antiepileptic drugs, but
the evidence related to the safety of substitution from brand name to generic
levetiracetam is scarce. The present study evaluated the risk of increased
frequency of seizures after replacement of a brand-name levetiracetam with a
generic product. METHODS: We enrolled patients with epilepsy who were treated
with branded levetiracetam for at least 6 months of sustained use. Patients were
advised to switch to the generic levetiracetam. We analyzed data from 6 months
before, to 6 months after, generic substitution. Increased seizure frequency was
defined as a>= 50% increase in seizure frequency after conversion date compared
with seizure frequency before the conversion date. We analyzed changes in seizure
frequency and performed subgroup analysis according to changes in seizure
frequency. RESULTS: We analyzed 148 epilepsy patients. Among the 148 patients,
109 (73.6%) were seizure-free before substitution and 105 patients remained
seizure-free after switching. After generic substitution, an increased seizure
frequency was noted in seven patients (4.7%), and a decreased seizure frequency
was noted in 10 (6.8%). Patients with decreased seizure frequency were
significantly younger (p = 0.035) than those with an unchanged seizure frequency.
CONCLUSION: This study suggests that the risk of increased seizure frequency
after generic substitution was minimal. The generic substitution of levetiracetam
was generally safe, although larger prospective studies are warranted to
corroborate our findings.
PMID- 29960218
TI - Integrating hepatitis C and addiction care for people who inject drugs in the era
of direct-acting antiviral therapy.
AB - As new, more tolerable and effective hepatitis C virus (HCV) treatments are
available, there is a global need to consider how to maximize treatment access
for groups who are most affected by HCV. A substantial number of people who
inject drugs (PWID) are living with HCV, yet only a minority have received
treatment. HCV treatment programs that are integrated into community-based
addiction care may be a successful way to overcome barriers and increase access
and uptake of HCV treatment for this population. Examples of successful HCV and
addiction care integration in the community have been documented. However,
potential challenges to integration exist and include changing healthcare
provider roles, lack of stimulant use research and restrictive drug policies.
Successful engagement of PWID in HCV care is critical step towards the
elimination of HCV infection. Further research and efforts are needed in order to
reach this goal.
PMID- 29960216
TI - Biophysical characterization of asolectin-squalene liposomes.
AB - Liposomes are shell nanoparticles able to embed hydrophobic molecules into their
lipid layers to be released to cells. In pharmaceutical sciences, liposomes
remain the delivery system with the highest biocompatibility, stability, loading
characteristics, tunable physicochemical properties. Squalene is a natural, water
insoluble, lipid, abundant in olive oil and shark liver. Studies in vitro and in
animal models suggest protective and inhibitory effects of squalene against
cancer. To study its effect on cells, and to overcome its insolubility in water,
we have designed and produced large unilamellar liposomes containing different
quantities of this terpene (0%, 2.8%, 5% w/w). Liposomes have been characterized
by different biophysical techniques. Size-exclusion and affinity chromatography
showed a unimodal size distribution and confirmed the squalene loaded dose.
Laurdan fluorescence evidenced the changes in the hydration of the external layer
of liposomes as a function of squalene concentration. Dynamic light scattering
and small angle X-ray scattering revealed squalene induced structural differences
in the hydrodynamic radius distribution and in the bilayer thickness
respectively. Finally, preliminary experiments on the effects of liposome
delivered squalene on tumor and non-tumor cell lines showed time- and dose
dependent cytotoxic effects on LAN5 tumor cells and no effect on NIH-3T3 normal
cells.
PMID- 29960219
TI - Continuous to discrete: Ensemble-based segmentation in the perception of multiple
feature conjunctions.
AB - Although objects around us vary in a number of continuous dimensions (color,
size, orientation, etc.), we tend to perceive the objects using more discrete,
categorical descriptions (e.g., berries and leaves). Previously, we described how
continuous ensemble statistics of simple features are transformed into
categorical classes: The visual system tests whether the feature distribution has
one or several peaks, each representing a likely "category". Here, we tested the
mechanism of segmentation for more complex conjunctions of features. Observers
discriminated between two textures filled with lines of various lengths and
orientations, which had same distributions between the textures, but opposite
directions of correlations. Critically, feature distributions could be
"segmentable" (only extreme feature values and a large gap between them) or "non
segmentable" (both extreme and middle values with smooth transition are present).
Segmentable displays yielded steeper psychometric functions indicating better
discrimination (Experiment 1). The effect of segmentability arises early in
visual processing (Experiment 2) and is likely to be provided by global sampling
of the entire field (Experiment 3). Also, rapid segmentation requires both
feature dimensions having a "segmentable" distribution supporting division of the
textures into categorical classes of conjunctions. We propose that observers
select items from one side (peak) of one dimension and sample mean differences
along a second dimension within the selected subset. In this scenario, subset
selection is a limiting factor (Experiment 4) of texture discrimination. Yet,
segmentability provided by the sharp feature distributions seems to facilitate
both subset selection and mean comparison.
PMID- 29960220
TI - Urinary concentrations of environmental phenols and their association with type 2
diabetes in a population in Jeddah, Saudi Arabia.
AB - A few epidemiologic studies suggest that exposure to bisphenol A (BPA) is
associated with type 2 diabetes mellitus (T2DM). However, little is known about
association between other phenolic endocrine disrupting chemicals (EDCs) and
T2DM. In this case-control study, we measured urinary concentrations of 23
phenolic EDCs in 101 individuals from Jeddah, Saudi Arabia, to examine the
association of parabens, antimicrobials, bisphenols, benzophenones and bisphenol
A diglycidyl ethers with T2DM. Urine samples were collected from 54 T2DM cases
and 47 non-diabetic individuals (controls), aged 28-68 years old, during 2015
2016. Unconditional logistic regression was performed to estimate odd ratios
(ORs) for the association between diabetes and EDC exposures after adjusting for
confounders including age, gender, nationality, smoking status and occupation.
Age from 40 to 59 years (OR 5.56, 95% CI 2.20-14.0) and smoking status (OR 2.92,
95% CI 1.25-6.79) showed significant positive associations with T2DM. After
adjusting for potential confounders, we found that T2DM cases had high urinary
levels of parabens (i.e., methyl- (MeP), ethyl- (EtP), propyl- (PrP) and 4
hydroxy benzoic acid (4-HB)), bisphenols (i.e., bisphenols A (BPA) and F (BPF)),
and benzophenone (i.e., 4-hydroxybenzophenone (4-OH-BP)) relative to the
controls. Individuals in the 4th quartile for urinary concentrations of MeP, EtP,
PrP, 4-HB and BPF and in the 3rd quartile for BPA and 4-OH-BP showed over a 6
fold increase in the odds of having diabetes compared with those in the first
quartile. Overall, our study shows that urinary levels of multiple phenolic EDCs
were associated with increased risk for diabetes. Further prospective studies are
required to verify these associations.
PMID- 29960221
TI - Integrating population connectivity into pollution assessment: Overwintering
mixing reveals flame retardant contamination in breeding areas in a migratory
raptor.
AB - Determining the exposure and magnitude at which various pollutants are
differentially assimilated at the breeding and non-breeding grounds of migratory
wildlife is challenging. Here, the possibility of applying the migratory
connectivity framework to understanding contamination in birds is illustrated by
considering flame retardants in inviable eggs of a migratory raptor, the black
kite (Milvus migrans). The occurrence and concentration of legacy and emerging
compounds in eggs from the southeastern peri-urban area of Madrid city, central
Spain, were compared with those from Donana National Park in southern Spain. A
much higher occurrence and concentration of multiple polybrominated diphenyl
ethers and Dechlorane 602 were found in Madrid than Donana, but the opposite
patterns were found for Dechlorane Plus. Individuals from these and other
breeding areas in western Europe showed a strong intermixing pattern over
widespread wintering areas in Africa, as assessed by ringing recoveries and
movements tracked by satellite devices. This diffuse migratory connectivity
reveals breeding areas as the main contamination grounds. High contamination
burdens sequestered in eggs point to rapid assimilation of these compounds before
laying, associated with important emission sources in Madrid, especially
landfills of partially incinerated urban refuse, and other anthropogenic
operations. Diet composition regarding aquatic vs. terrestrial prey, and
bioaccumulation and biomagnification processes are suggested to explain
differential assimilation of some compounds, especially Dechlorane Plus in
Donana, although a local emission source polluting this area cannot be ruled out.
Insight from the migratory connectivity framework can help to disentangle large
scale patterns of contaminant uptake and refocus attention on key regions and
potential causes of chemical hazards in declining migratory species and human
populations.
PMID- 29960222
TI - Potential association between exposure to legacy persistent organic pollutants
and parasitic body burdens in Indo-Pacific finless porpoises from the Pearl River
Estuary, China.
AB - A high prevalence of infectious diseases (mostly lungworms) is found in finless
porpoises (genus Neophocaena) in the coastal waters of China, which is one of the
most dichlorodiphenyltrichloroethane (DDT)-polluted areas worldwide, while its
association with contaminant exposure remains undetermined. To address this gap,
we investigated blubber levels of polychlorinated diphenyls (PCBs),
organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons in Indo
Pacific finless porpoises (Neophocaena phocaenoides) stranded in the Pearl River
Estuary (PRE) of China. In the post-mortem examinations, lungworms (Halocercus
species) were found to be the most common parasites, with a high density observed
in lungs and bronchi. Severe infections by nematode parasites were also found in
the uterus (Cystidicola species), intestine (Anisakis typica) and muscle (A.
typica). For all the pollutant compounds analyzed, only the concentrations of
p,p'-DDT, p,p'-dichlorodiphenyldichloroethane (DDD) and o,p'-DDD were
significantly higher in porpoises died of infectious diseases than in the
"healthy" individuals (died from physical trauma). Contrasted accumulation
pattern of DDTs and their metabolites was found between animals with different
health status. The proportion of p,p'-DDT in SigmaDDTs was higher than that of
p,p'-dichlorodiphenyldichloroethylene (DDE) in diseased animals, whereas an
opposite pattern was shown for "healthy" ones. While this study is the first to
describe a significant positive correlation between parasitic diseases and high
levels of DDTs in cetaceans, the direction of causality cannot be determined in
our data: either a parasitic infection affected the porpoises' ability to
metabolize DDTs, resulting in high levels of p,p'-DDT in their blubber, or the
pollutant burden rendered them more susceptible to parasitic infection.
PMID- 29960223
TI - Environmental strains potentially contribute to the proliferation and maintenance
of antibiotic resistance in drinking water: A case study of Cupriavidus
metallidurans.
AB - Fitness costs of antibiotic resistance detrimentally affect the fate of
resistance carriers. Intriguingly, numerous antibiotic resistant bacteria (ARB)
have been detected despite the low concentration of antibiotics in drinking
water. To reveal the causes of this discrepancy, we investigated the fitness cost
of antimicrobial resistance in strain Cupriavidus metallidurans CR2 which was
isolated from a drinking water filter. Pure culture and 1:1 competitive
experiments were established at different nutrient levels. The growth rates of
strain C. metallidurans CR2 significantly decreased when pure cultured under poor
nutrient conditions, however, the multi-resistance and the resistance
megaplasmids were well maintained. Competitiveness costs were observed in C.
metallidurans when separately co-cultured with environmentally-isolated
Flectobacillus BS1 and Pseudomonas sp. S3, while C. metallidurans was outnumbered
by the rivals with a decrease of 1-2 logs. But the majority of C. metallidurans
retained the plasmids under oligotrophic conditions even after 144 h (1.99 and
0.199 mg C/L). Additionally, C. metallidurans CR2 has a higher tolerance to
chlorine and chloramine, which potentially could become prevalent in the
subsequent distribution systems other than drinking water treatment plant. As a
potential pathogen, the prevalence of Cupriavidus metallidurans in drinking water
would also pose certain threats to human health.
PMID- 29960224
TI - Biogeochemistry and sedimentology of Lago di Lesina (Italy).
AB - The Lago di Lesina (Lesina Lake, southeastern Italy) is a coastal pond located on
an alluvial plain to the north of Gargano Promontory. The aim of this work was to
study the depositional and hydrological processes, the benthic environment and
the heavy metal sediments pollution of Lesina Lake. The study was carried out by
Redox potential, water content, grain-size, mineralogical and biogeochemical
analyses in surface sediments collected from 100 sampling stations in the coastal
pond bottom. The results showed a predominance of three types of bottom pelitic
sediments of different origins and compositions: siliciclastic, carbonatic, and
organic. Siliciclastic sediments, which were found especially in the western
basin and in the northwestern sector of the central basin, are due to inputs from
Acquarotta Canal, some intermittent western streams, and deflation by northerly
winds of the sandy barrier that separates the lake from the sea. Carbonate
sediments are carried by streams and canals draining the carbonate rocks of the
Gargano Mountains and entering the lake from its eastern and southeastern border,
these sediments are predominant in the eastern basin and in the southeastern
sector of the central basin. Organic matter is abundant throughout the whole
lake; it is due to the high productivity of the Lago di Lesina waters that are
rich of nutrients for inputs of waters draining the surrounding intensively
cultivated agricultural areas. The finer bottom sediments of the lake tend to be
removed from the shallower bottoms between the central and eastern sub-basins and
near the borders to be deposited in the central portion of the central and
western sub-basins. Heavy metal sediment pollution due to anthropic inputs is
limited and consists of As, Pb, Cu, and Ni in the western basin, Cu, Zn, and Ni
in the eastern basin, and Pb along the northern border.
PMID- 29960225
TI - Stressor-driven emigration and recolonisation patterns in disturbed habitats.
AB - Although essential to conservation, little is known about how stress intensity
can provoke emigration from disturbed habitats and allow recolonisation of those
same environments. To demonstrate the applicability of laboratory experiments, we
tested two hypotheses empirically using zebrafish response to artificially
polluted environments that exhibited a linear gradient of stressor (acid mine
drainage) levels. We hypothesized that emigration is distance-independent but
time-correlated (spacelessness hypothesis). Additionally, we hypothesized that
stressor-driven emigration could predict the extent of population growth in
recovering habitats (avoidance-recolonisation hypothesis). For example, if half
the organisms emigrate at a given stressor level, then the remainder should be
able to recolonise a habitat experiencing the same stressor intensity.
Comparisons of the small-scale experiment with a larger-scale simulation
suggested that controlled laboratory results can be extrapolated to field
populations (although time to perceive the contamination gradient may pose
differential individual effects) because AC50 (median avoidance concentration)
values of an acid mine drainage sample (AMD) were not statistically different
when fish were exposed to the same gradient in 3-m long [0.50% (0.43-0.57)] or 30
m long [0.73% (0.30-2.2)] systems. Regarding the avoidance-recolonisation
hypothesis, the number of recolonisers was inversely proportional to the number
of avoiders (ACx = RC100-x). In particular, the similar distribution of fish
along the 0-3% AMD gradient in both avoidance and recolonisation experiments
resulted in identical AC50 and RC50 values: 0.55% (0.34-0.87) and 0.55% (0.45
0.67) AMD, respectively. The inclusion of avoidance and recolonisation responses
in the environmental risk assessments provides a novel perspective of risk based
on the emigration of organisms and contributes to the understanding and
prediction of biological invasions and ecosystem recovery after restoration.
PMID- 29960226
TI - A comparison of disaggregated nitrogen budgets for Danish agriculture using
Europe-wide and national approaches.
AB - Spatially detailed information on agricultural nitrogen (N) budgets is relevant
to identify regions where there is a need for a reduction in inputs in view of
various forms of N pollution. However, at the scale of the European Union, there
is a lack of consistent, reliable, high spatial resolution data necessary for the
calculation of regional N losses. To gain insight in the reduction in uncertainty
achieved by using higher spatial resolution input data. This was done by
comparing spatially disaggregated agricultural N budgets for Denmark for the
period 2000-2010, generated by two versions of the European scale model
Integrator, a version using high spatial resolution national data for Denmark
(Integrator-DK) and a version using available data at the EU scale (Integrator
EU). Results showed that the national N fluxes in the N budgets calculated by the
two versions of the model were within 1-5% for N inputs by fertilizer and manure
excretion, but inputs by N fixation and N mineralisation differed by 50-100% and
N uptake also differed by ca 25%, causing a difference in N leaching and runoff
of nearly 50%. Comparison with an independently derived Danish national budget
appeared generally to be better with Integrator-EU results in 2000 but with
Integrator-DK results in 2010. However, the spatial distribution of manure
distribution and N losses from Integrator-DK were closer to observed
distributions than those from Integrator-EU. We conclude that close attention to
local agronomic practices is needed when using a leaching fraction approach and
that for effective support of environmental policymaking, Member States need to
collect or submit high spatial resolution agricultural data to Eurostat.
PMID- 29960227
TI - Carbon uptake by European agricultural land is variable, and in many regions
could be increased: Evidence from remote sensing, yield statistics and models of
potential productivity.
AB - Agricultural plants, covering large parts of the global land surface and
important for the livelihoods of people worldwide, fix carbon dioxide seasonally
via photosynthesis. The carbon allocation of crops, however, remains relatively
understudied compared to, for example, forests. For comprehensive consistent
resource assessments or climate change impact studies large-scale reliable
vegetation information is needed. Here, we demonstrate how robust data on carbon
uptake in croplands can be obtained by combining multiple sources to enhance the
reliability of estimates. Using yield statistics, a remote-sensing based
productivity algorithm and climate-sensitive potential productivity, we mapped
the potential to increase crop productivity and compared consistent carbon uptake
information of agricultural land with forests. The productivity gap in Europe is
higher in Eastern and Southern than in Central-Western countries. At continental
scale, European agriculture shows a greater carbon uptake in harvestable
compartments than forests (agriculture 1.96 vs. forests 1.76 t C ha-1 year-1).
Mapping productivity gaps allows efforts to enhance crop production to be
prioritized by, for example, improved crop cultivars, nutrient management or pest
control. The concepts and methods for quantifying carbon uptake used in this
study are applicable worldwide and allow forests and agriculture to be included
in future carbon uptake assessments.
PMID- 29960228
TI - Assessing environmental flows of coordinated operation of dams and weirs in the
Geum River basin under climate change scenarios.
AB - The International Panel on Climate Change (IPCC) has predicted frequent and
severe droughts and floods caused by irregular climatic conditions in the future,
making water resources management difficult. Within the field of integrated
watershed management, the concept of 'environmental flow' is being increasingly
studied. In Korea, the Four Major Rivers Restoration Project was carried out as
part of the plan to manage future water resources, particularly in response to
climate change. In order to improve comprehensive water resources management,
there is an interest in integrating into the operation of the existing dams the
multi-functional weirs constructed under the said project. To date, there is an
absence of studies comprehensively considering climate change, run-off volume,
reservoir operations, and environmental flow, with most of the existing studies
focusing only on one or the other of these factors. In this study, we presented a
method to evaluate the river environment that considers all the said factors. To
evaluate how environmental flow is influenced by the changes in river flow due to
climate change and hydraulic structure operation, the Streamflow Synthesis and
Reservoir Regulation (SSARR) was used as the hydrological model, HEC-ResSim was
used as the hydraulic structures operational model, and the Global Environmental
Flow Calculator (GEFC) was used as the method to evaluate environmental flows.
RCP climate change scenarios, provided by the Climate Change Information Center
(CCIC), a branch of the Korea Meteorological Administration, were applied to
analyze the future watershed runoff characteristics of the Geum River Basin under
different hydraulic structure operation modes. This study concludes that
efficient use of water resources can be achieved through the integrated operation
of the dams and multi-functional weirs in times of water shortage. Comparing the
results of modelling under a no-carbon reduction scenario on one hand, and a
scenario in which emissions were reduced on the other hand, differences were
found in flows during floods, in the mean annual runoff ratio in accordance with
the environment management class, and in the environmental flow rating. It
appears that a new water resources management plan is required to respond to
climate change as indicated by the shift of the flow duration curve to a lower
environmental management class (EMC) under climate change scenarios.
PMID- 29960229
TI - Responses of soil microbial community structure changes and activities to biochar
addition: A meta-analysis.
AB - The objective of this study was to investigate responses of soil microbial
community structure changes and activities to biochar addition under different
biochar characteristics, soil properties, and experiment conditions. A meta
analysis was conducted based on 265 datasets from 49 published studies. Results
showed that biochar addition significantly increased the ratios of soil fungi to
bacteria (F/B) and the ratios of Gram-positive bacteria to Gram-negative bacteria
(G+/G-), and microbial biomass and activities. The enhancement of F/B ratios was
most significant with addition of biochars produced at low temperatures to soils
with lower pH and nutrients in a long-term condition, which improved ecosystem
stability of agricultural soils. The F/B ratios were mainly affected by biochar
nutrients, soil nutrients, and soil pH values. Biochar nutrients and structural
properties (i.e., surface area and porosity) also played the important role in
enhancing G+/G-, total microbial biomass, and activities of bacteria, fungi, and
actinomycetes. The G+/G- ratios increased the most with addition of biochars
produced with medium temperatures and residue accompanied with fertilizers in dry
land (dried farmland) soils. High biochar load greatly improved the total
phospholipid fatty acids, and activities of bacteria, fungi, and actinomycetes in
fine/coarse, paddy soils, and soils with low nutrients, in turn increased the
soil nutrient cycling. In addition, the structural properties of biochars were
the most influencing factor to increase total microbial biomass and actinomycete
activity. Overall, the enhancement of microbial activities and community
structure shifts under biochar addition should promote soil nutrients cycling and
carbon sequestration, and improve crop yields.
PMID- 29960230
TI - Effect of suspended solids on peracetic acid decay and bacterial inactivation
kinetics: Experimental assessment and definition of predictive models.
AB - The work addresses the effect of total suspended solids (TSS) on disinfection by
peracetic acid (PAA) concerning both PAA decay and bacterial inactivation
kinetics. The effect of TSS on PAA decay was evaluated at five TSS concentrations
(5, 40, 80, 120 and 160 mg/L), obtained from stock TSS solutions prepared from
activated sludge samples. The influence of the soluble matter associated to the
suspended solids on PAA decay was evaluated separately, using the same stock TSS
solution after the removal of solids by filtration. The contributions of
suspended and soluble fractions were found to be independent, and a predictive
model formed by two additive sub-models was proposed to describe the overall PAA
decay kinetics. Moreover, an uncertainty analysis was performed by a series of
Monte Carlo simulations to propagate the uncertainties associated to the
coefficients of the model. Then, the disinfectant dose (mg/L min) was highlighted
as the main parameter determining disinfection efficiency on a pure culture of E.
coli and an inactivation kinetic model was developed based on the response of E.
coli to various PAA doses. Finally, the effect of TSS (40 and 160 mg/L) on the
inactivation of free-swimming E. coli was investigated at two PAA doses (5 and 20
mg/L min). TSS reduced inactivation extent an average of 0.4 logs at 5 mg/L min
and 1.5 logs at 20 mg/L min. It was hypothesized that this might be due to the
formation of bacteria aggregates as defense mechanism against disinfection,
enhanced by the presence of solids.
PMID- 29960231
TI - Effects of ocean acidification on the levels of primary and secondary metabolites
in the brown macroalga Sargassum vulgare at different time scales.
AB - Most of the studies regarding the impact of ocean acidification on macroalgae
have been carried out for short-term periods, in controlled laboratory
conditions, thus hampering the possibility to scale up the effects on long-term.
In the present study, the volcanic CO2 vents off Ischia Island were used as a
natural laboratory to investigate the metabolic response of the brown alga
Sargassum vulgare to acidification at different time scales. For long-term
effects, algal populations naturally growing at acidified and control sites were
compared. For short-term responses, in situ reciprocal transplants from control
to acidified site and vice-versa were performed. Changes in the levels of sugars,
fatty acids (FAs), amino acids (AAs), antioxidants, and phenolic compounds were
examined. Our main finding includes variable metabolic response of this alga at
different time scales to natural acidification. The levels of sugars, FAs, and
some secondary metabolites were lower in the natural population at the acidified
site, whereas the majority of AAs were higher than those detected in thalli
growing at control site. Moreover, in algae transplanted from control to
acidified site, soluble sugars (glucose and mannose), majority of AAs, and FAs
increased in comparison to control plants transplanted within the same site. The
differences in the response of the macroalga suggest that the metabolic changes
observed in transplants may be due to acclimation that supports algae to cope
with acidification, thus leading to adaptation to lowered pH in long time scale.
PMID- 29960232
TI - Measurements of atmospheric HONO vertical distribution and temporal evolution in
Madrid (Spain) using the MAX-DOAS technique.
AB - Nitrous acid (HONO) stands as one of the main species in tropospheric chemistry,
primarily in polluted, urban regions. Due to its fast photodissociation, it is
considered as one the main sources of the hydroxyl radical (OH), the most
relevant oxidant in the atmosphere. Therefore, the evaluation of HONO
concentration profiles and their temporal evolution is important for urban
atmospheric chemistry. In this study, we report a year-round measurement of HONO
vertical concentration profiles, as well as their diurnal and seasonal evolution
during 2016 in Madrid. Making use of the Multi-AXis Differential Absorption
Spectroscopy (MAX-DOAS) technique in addition to inversion algorithms, we
retrieved the aerosol extinction and trace gas concentrations. Our results show
HONO maximum values of 3.5-4 ppbv in the early morning and late afternoon, and
minima around noon, when the lifetime of HONO against photolysis is shortest. On
average, there is a pronounced HONO concentration gradient across different
seasons, being higher during the autumn and winter months. Finally, we estimate
and discuss the production rate of OH radicals from HONO photolysis, along with
its variability throughout the year.
PMID- 29960233
TI - Distribution, formation and human-induced evolution of geogenic contaminated
groundwater in China: A review.
AB - The sustainability of groundwater usage faces quality problem caused by
anthropogenic activity as well as geogenic contamination. With varied climate
zones, geomorphology and geological background, China faces a variety of geogenic
contaminated groundwater (GCG) reported known as high TDS, Fe, Mn, As, F, I,
NH4+, U, Cr and low I, Se, etc., may still exist some others not fully known yet.
The problem of GCG is more significant in northern China due to extensive
groundwater usage, arid climate and widespread Holocene strata. High salinity
groundwater is mainly distributed in semi-arid/arid northwestern inland basins
and coastal areas. Elevated Fe and Mn are frequently concomitant and controlled
by redox potential, prevailing in the Sanjiang Plain, Yellow River Basin, and
middle and lower reaches of the Yangtze River Basin. High As groundwater occurs
in reducing aquifer is mainly distributed in the Yellow River, Yangtze River and
Huai River Basins as well as the Songnen Plain and Xinjiang. Fluoride is
characterized by its areal distribution in northern China in comparison with
scatter occurrence in the south. The dissolution of F-bearing minerals as well as
evaporation effect both contribute to elevated F. High iodine groundwater mainly
distributed in the Yellow-Huai-Hai River Basin and low iodine prevailing in
piedmont areas both pose health issues. Iodine is related to decomposition of
organic matter (OC) as well as marine origin. Contributed by OC mineralization
naturally-occurring NH4+ was found in reducing aquifers. The GCG triggers endemic
disease in addition to reduce groundwater resource. The co-occurrence like high
TDS and F, As and F are frequently observed posing major challenges for
mitigation. Anthropogenic influence like abstraction and pollutant infiltration
would alter groundwater flow and the redox condition causing the further
evolution of GCG. Identification of GCG should be made in rural areas where
private wells prevail to ensure resident's health.
PMID- 29960234
TI - Carbon dots coated with molecularly imprinted polymers: A facile bioprobe for
fluorescent determination of caffeic acid.
AB - A new and sensitive method for fluorescent determination of caffeic acid (CA) was
proposed based on silane-functionazed carbon dots coated with molecularly
imprinted polymers (CDs@MIPs). CDs@MIPs were prepared by using CA as the
templates on the surface of silane-functionazed carbon dots(CDs) with a sol-gel
process. The as-prepared CDs@MIPs were characterized by Fourier transform
infrared spectroscopy, transmission electron microscopy and fluorescence
spectroscopy. The CDs@MIPs exhibited distinguished selectivity and high binding
affinity to CA templates, and also showed good reusability. Under optimal
conditions, the fluorescence intensity of CDs@MIPs decreased linearly with the
increase of CA in the range of 0.5-200 MUM. The limit of detection was 0.11 MUM
(3sigma/K). Finally, the proposed method was successfully applied to the
detection of CA in human plasma. The result indicates that the method built has
promising potential for monitoring CA concentration in clinic.
PMID- 29960235
TI - Formation and dispersion of organometal halide perovskite nanocrystals in various
solvents.
AB - The solvent-induced precipitation in a mixture of good and poor solvents was
often used to synthesize organometal halide perovskite nanocrystals (OMHP NCs).
Here we investigate the formation of OMHP NCs by using HBr based precursors in
various solvents. Various emission colors and morphologies of perovskite NCs were
obtained depending on the solvents used. The nanoplatelets with blue emission
were produced for the low polar solvents, such as toluene, PhCl and EtOAc. The
increase in polarity of poor solvents results in the red shift of emission of
obtained NCs. The much more polar solvents like acetone and CH3CN lead to
formation of CH3NH3PbBr3 NCs (MaPbBr3) with cubic phase. The dispersion behaviors
of MaPbBr3 NCs in different solvents was also investigated. MaPbBr3 NCs can exist
stably in most unpolar solvents. However, they will be dissolved in polar
solvents, like acetone and acetonitrile, to give rise to a clear solution with
red emission of Pb2+. By injecting this clear solution to unpolar solvents, OMHP
NCs can be reproduced.
PMID- 29960236
TI - Wetting behavior of four polar organic solvents containing one of three lithium
salts on a lithium-ion-battery separator.
AB - HYPOTHESIS: The wetting behavior of an electrolyte solution on the separator,
determined by contact-angle measurements, has a significant effect on the
internal resistance of the battery and on its cycle life. The solvent, the
lithium-salt type and its concentration may affect the wettability. However, few
systematic studies address the effect of salt concentration on surface tension
and contact angle. EXPERIMENTS: Surface tensions and advancing contact angles
were measured for dimethyl sulfoxide (DMSO), propylene carbonate (PC), dimethyl
carbonate (DMC), and a PC/DMC mixture (1:1 mass ratio) with various
concentrations of a lithium salt (LiClO4, LiPF6, and LiTFSI) at 23 degrees C.
Measurements were made by a Kruss Drop Shape Analyzer 100, with a video camera
mounted on a microscope to record the drop image. FINDINGS: For DMSO, PC and
PC/DMC, surface tensions increase by adding LiClO4 or LiPF6 but decrease upon
addition of LiTFSI. For DMC, the lithium salts have little impact on the surface
tensions. For each solvent, contact angles and adhesion energies follow the same
trend as those for surface tensions. The TFSI- anion reduces the surface tension
of the solvent, favoring good wettability of the separator. The optimal surface
tension for wettability of Celgard 2500 is at or below 26.1 mN/m.
PMID- 29960237
TI - Chemometrics-assisted study of the interconversion between the crystalline forms
of nimodipine.
AB - Nimodipine (NIM) is a calcium channel-blocking agent, which in the solid state
exhibits two crystalline modifications, Mode I and Mode II. The first one is a
racemic mixture, while the second is a conglomerate. Because the drug has poor
aqueous solubility and Mode I is twice as soluble as Mode II, the former is
widely preferred for the development of pharmaceutical forms. In order to study
the effect of thermal stimuli on the behavior of NIM, an analytical method was
developed coupling ATR-FTIR spectroscopy to Multivariate Curve Resolution with
Alternating Least Squares (MCR-ALS). The method allowed to monitor the
transformations of each polymorph, their respective mixtures and commercial
samples, during the thermal treatment. It was observed that Mode II experienced
changes during the experiments and the chemometric technique provided the
abundance profile and the pure spectra of the different species involved. In this
way, it was established that Mode II has two transitions, at 116.8 degrees C and
131.9 degrees C, which reflect that Mode II is first transformed into Mode I,
which then melts. The liquid phase solidifies to give an amorphous (AM) vitreous
solid, which does not revert to the crystalline state. The analysis of a
commercial sample of NIM exhibited the similar transformations than Mode II;
however, a pronounced decrease was noted in the first transition temperature (95
degrees C), whereas the second remained essentially unchanged (131.6 degrees C).
This could be a result of the presence of mixtures of Mode I and Mode II
(0.32:0.68) in the bulk solid, as confirmed by the analysis of a physical mixture
of crystals of Modes I and II. Therefore, it was concluded that the developed ATR
FTIR/MCR-ALS method is suitable for the detailed analysis of the crystalline
forms of NIM in bulk drug and enables de study of their possible thermally
promoted interconversions.
PMID- 29960238
TI - Acetylcholinesterase-inhibitory activity of Iranian plants: Combined
HPLC/bioassay-guided fractionation, molecular networking and docking strategies
for the dereplication of active compounds.
AB - In order to search for discovery of acetylcholinesterase (AChE) inhibitors, as a
therapeutic strategy for treatment of the Alzheimer's disease, twenty-five
Iranian plants have been evaluated by an in vitro enzymatic Ellman method and
molecular docking study. Each plant was successively extracted by n-hexane, ethyl
acetate and methanol to obtain a total of 75 extracts. The inhibiting effect of
extracts was measured by a colorimetric assay in 96-well microplates. The n
hexane extract of Prangos ferulacea showed the highest AChE inhibitory activity
with 75.6% inhibition at a concentration of 50 MUg/mL. The chemical composition
of this extract was investigated in detail based on a combination of
HPLC/bioassay-guided fractionation and molecular networking techniques. The
results led to the identification of seventeen compounds, one of them was a fatty
acid derivative, two compounds had flavonoid structure and others were
furanocoumarin type compounds. In vitro analysis showed that the subfraction F10f
was the most potent inhibitor against the activity of AChE with an IC50 value of
25.2 MUg/mL and good docking scores of its constituents confirming its high
activity.
PMID- 29960239
TI - Gold nanoparticles coupled with graphene quantum dots in organized medium to
quantify aminoglycoside anti-biotics in yellow fever vaccine after solid phase
extraction using a selective imprinted polymer.
AB - The determination of kanamycin sulfate was made indirectly by measuring its
effect on photoluminescent amino functionalized graphene quantum dots (GQDs
amino) associated with gold nanoparticles (AuNPs) that were produced by the
reduction of AuCl4 with NaBH4 in an aqueous dispersion of GQDs-amino (obtained by
the pyrolysis of citric acid and glutathione) also containing the cationic
surfactant CTAB. The AuNPs-GQDs-amino-CTAB system presents a suppressed
photoluminescence that is amplified in the presence of kanamycin. Under optimized
experimental conditions, the photoluminescence amplification of the nanomaterial
system showed a linear response as a function of kanamycin concentration,
covering three orders of magnitude (10-7 to 10-5 mol L-1). The use of solid phase
extraction with a cartridge packed with aminoglycoside selective molecularly
imprinted polymer ensured selectivity in determinations made on yellow-fever
vaccine and veterinary pharmaceutical formulations. The analytical results were
statistically similar to those obtained with an HPLC-based fluorescence method
(after chemical derivatization). The proposed method is a simple, sensitive and
selective approach that does not involve the use of toxic reagents employed for
chemical derivatization of aminoglycoside antibiotics.
PMID- 29960240
TI - Synthesis and SERS activity of super-multibranched AuAg nanostructure via silver
coating-induced aggregation of nanostars.
AB - The super-multibranched AuAg bimetallic nanostructures are synthesized due to the
aggregation of Au nanostars in the process of silver coating. The super
multibranched bimetallic nanostructures with different silver coating thickness
are obtained by changing the concentration of silver nitrate and ascorbic acid.
It has been found that the formation of these nanostructures is due to the
stacking of several nanostars during the process of silver coating. By comparing
the silver coating process of gold nanostars with different branch lengths, we
found that the nanostars with longish branches are easy to aggregate and form the
super-multibranched nanostructures in the process of silver coating. In the AuAg
bimetallic nanostructures, the silver layer is mainly covered on the surface of
the cores and the thickness increases with the increasing of the AgNO3, which
leads to the change of the surface-enhanced Raman scattering (SERS) activity. It
has been found that the SERS activity is stronger when the silver layer is thin
and the Au branches are still exposed to the outside of the Ag shell. The sample
with the strongest SERS activity has been used to detect thiram with different
concentrations. The Raman intensity increases linearly with the logarithmic
concentration of thiram ranging from 10-3 to 10-7 M with a detection limit of 6.3
* 10-7 M. These experimental results show that the super-multibranched bimetallic
nanostructures have a broad application prospect in molecular detection and
biologic sensing based on SERS.
PMID- 29960241
TI - Luminescent and electrochemical properties of four novel butterfly-shaped hetero
pentanuclear [Zn4Ln] complexes constructed from a bis(salamo)-type ligand.
AB - Four novel butterfly-shaped hetero-pentanuclear 3d-4f complexes
[Zn4(L)2Sm(H2O)4]3NO3.2EtOH (1) [Zn4(L)2Eu(NO3)2(MeOH)(EtOH)]NO3.H2O (2),
[Zn4(L)2Gd(H2O)4]3NO3.MeOH.EtOH (3) and [Zn4(L)2Tb(NO3)(EtOH)(H2O)2]NO3.MeOH.EtOH
(4) were synthesized by the reactions of a bis(salamo)-type tetraoxime ligand
(H4L) with Zn(OAc)2.2H2O and Ln(NO3)3.6H2O (Ln = Sm, Eu, Gd and Tb),
respectively. The structures of complexes 1-4 were fully characterized by
elemental analyses, FT-IR, UV-Vis spectroscopy and single crystal X-ray
crystallography, and their luminescence properties were also discussed. In
addition, cyclic voltammograms were used to characterize electrochemical
properties of the Zn(II)-Ln(III) (Ln = Sm, Eu, Gd and Tb) complexes.
PMID- 29960242
TI - Biosynthesis of pyruvic acid from glycerol-containing substrates and its
regulation in the yeast Yarrowia lipolytica.
AB - The ability of different yeasts to synthesize pyruvic acid (PA) from glycerol
containing substrates has been studied. The selected strain Yarrowia lipolytica
VKM Y-2378 synthesized PA with alpha-ketoglutaric acid (KGA) as a byproduct. The
content of KGA greatly depended on cultivation conditions. The minimal formation
of the byproduct was provided by the limitation of yeast growth by thiamine (0.6
ug/g biomass); the use of ammonium sulfate (0.6%) as a nitrogen source; addition
of glycerol to cultivation medium in 20 g/L portions; maintaining the cultivation
temperature at 28 degrees C, pH of the cultivation medium at 4.5, and medium
aeration between 55 and 60% of saturation; the optimal cultivation time was 48 h.
The selected strain cultivated under such conditions in a fermenter with a waste
glycerol from biodiesel production process synthesized 41 g/L PA with a yield of
0.82 g/g. The mechanism of PA production from glycerol-containing substrates in
Y. lipolytica is discussed.
PMID- 29960243
TI - Spent substrate of Ganodorma lucidum as a new bio-adsorbent for adsorption of
three typical dyes.
AB - Spent substrate of Ganodorma lucidum (SSGL), waste from cultivation of Ganoderma
lucidum, was firstly used as a bio-adsorbent to adsorb three typical dyes
malachite green, safranine T and methylene blue, and the adsorption
thermodynamics and dynamics were also studied. SSGL was rich of hydroxyl group
and carbonyl group, which had the potential to be an efficient bio-adsorbent for
the three dyes removal from water and wastewater, and the treatment model should
be eco-friendly. The experimental data fit well with the Langmuir and Freundlich
isotherm, and the adsorption of dyes took place mainly on monolayer surface of
SSGL. The experimental data fit also well with the adsorption thermodynamics, the
adsorption were spontaneous and mainly a chemical adsorption. SSGL could adsorb
the dyes rapidly and achieve an equilibrium in a short time, and the experimental
data fit well with the second-order kinetics model.
PMID- 29960244
TI - Cr(III) removal from synthetic and industrial wastewaters by using co
gasification chars of rice waste streams.
AB - Blends of rice waste streams were submitted to co-gasification assays. The
resulting chars (G1C and G2C) were characterized and used in Cr(III) removal
assays from a synthetic solution. A Commercial Activated Carbon (CAC) was used
for comparison purposes. The chars were non-porous materials mainly composed by
ashes (68.3-92.6% w/w). The influences of adsorbent loading (solid/liquid ratio -
S/L) and initial pH in Cr(III) removal were tested. G2C at a S/L of 5 mg L-1 and
an initial pH of 4.50 presented an uptake capacity significantly higher than CAC
(7.29 and 2.59 mg g-1, respectively). G2C was used in Cr(III) removal assays from
an industrial wastewater with Cr(III) concentrations of 50, 100 and 200 mg L-1.
Cr(III) removal by precipitation (uptake capacity ranging from 11.1 to 14.9 mg g
1) was more effective in G2C, while adsorption (uptake capacity of 16.1 mg g-1)
was the main removal mechanism in CAC.
PMID- 29960245
TI - Fast start-up of the single-stage nitrogen removal using anammox and partial
nitritation (SNAP) from conventional activated sludge in a membrane-aerated
biofilm reactor.
AB - The single-stage nitrogen removal using anammox and partial nitritation (SNAP) is
a promising alternative for low-cost ammonium removal from wastewaters. This
study aimed to evaluate the anammox biomass enrichment and SNAP process start-up
in a laboratory-scale membrane-aerated biofilm reactor (MABR) at nitrogen loading
rates of 50 g N.m-3.d-1 (period 1) and 100 g N.m-3.d-1 (period 2). Anammox
activity was observed after 48 days, and the SNAP process was stable after 80
days. In period 1, the average total nitrogen (TN) removal was 78 +/- 6%, and the
maximum removal was 84%. In period 2, the average TN removal was 61 +/- 5%, and
the maximum was 69%. Higher dissolved oxygen levels may have caused imbalances in
the microbial community in period 2, decreasing the reactor performance. These
results demonstrated the potential of the MABR for the fast implementation of the
single-stage partial nitritation and anammox processes.
PMID- 29960246
TI - Exploring the effects of galantamine paired with meditation and dream reliving on
recalled dreams: Toward an integrated protocol for lucid dream induction and
nightmare resolution.
AB - An experimental home study examined the impact of a pre-sleep protocol for
enhancing self-awareness, lucidity, and responsiveness in dreams. It included
ingesting the cholinesterase inhibitor galantamine--which is widely reported to
increase the frequency of lucid dreaming--prior to engaging in middle-of-the
night meditation and the imaginary reliving of a distressing dream while
exercising new responses. Thirty-five participants completed an eight-night
study, which included pre- and post-baseline nights and six conditions: waking
for 40 min before returning to bed, called Wake-Back-to-Bed (WBTB); Wake-Back-to
Bed plus placebo (WBTB + P); Wake-Back-to-Bed plus galantamine (WBTB + G);
meditation and dream reliving (MDR); meditation and dream reliving plus placebo
(MDR + P); and meditation and dream reliving plus galantamine (MDR + G). The
outcome measures included lucidity, reflectiveness, interactive behavior, role
change, constructive action, and fear and threat, as measured by the
participants' self-ratings. The results support the use of this protocol in
further studies of lucid dream induction and nightmare/trauma resolution.
PMID- 29960247
TI - Bond strength of resin cement to zirconia treated in pre-sintered stage.
AB - PURPOSE: Aim of this study was to evaluate the tensile bond strength (TBS)
between resin cement and zirconia surface treated in different sintering stages.
MATERIALS AND METHODS: Eighty zirconia discs having final dimensions of 12 mm
diameter and 3.2 mm thickness were milled then divided into three main groups
according to the type of surface treatment performed (group 1: air abrasion using
50 um Al2O3 particles, group 2: silica coating using Rocatec soft, and group 3: a
control group receiving no surface treatment). Groups 1 and 2 were divided into
two subgroups each according to the stage in which the surface treatment was
performed (subgroup A; surface treatment performed in the pre-sintered stage and
subgroup B; surface treatment performed in the post-sintered stage). Discs were
later bonded to composite core materials using resin cement then tested for TBS
either being subjected to 3 days of water storage or 150 days of water storage
and 37,500 thermal cycles. RESULTS: Long-term aging caused a significant decrease
in TBS of all subgroups except the subgroup air-abraded in the post-sintered
stage. After long-term aging, the group silica coated in the pre-sintered stage
showed the significantly lowest TBS compared to all other groups. There was also
no significant difference between the subgroups air-abraded and silica coated in
the pre-sintered stage. All specimens in the control group debonded during long
term aging. SIGNIFICANCE: Air-abrading zirconia with Al2O3 at a reduced pressure
in the pre-sintered stage may result in durable bond strength to resin cement.
PMID- 29960248
TI - Influence of microscale expansion and contraction caused by thermal and
mechanical fatigue on retentive strength of CAD/CAM-generated resin-based
composite crowns.
AB - CAD/CAM-generated resin-based composite crowns have been proposed as an
inexpensive alternative to conventional crowns. However, concerns have been
raised about crown loosening in clinical use. Therefore, the present in vitro
study aimed to evaluate the influence of thermal and mechanical cycling (TC and
MC) on retentive strength of CAD/CAM resin-based crowns in relation to microscale
expansion and contraction caused by fatigue. Eighty standardized dies were
produced using a resin-based composite material. Crowns were milled from resin
based composite (n = 40) and glass-ceramic blocks (n = 40; control) using a
dental CAD/CAM system. The crowns bonded to the dies were subjected to TC
(temperature: 5 and 55 degrees C, cycles: 50,000) and MC (load: 200 N, cycles:
1.2 million). After fatigue treatment, retentive strength of the crowns was
evaluated by a crown pull-off test at a crosshead speed of 1 mm/min. Coefficient
of thermal expansion (CTE) and modulus of elasticity (E-modulus) of each material
were also analyzed to estimate the microscale expansion and contraction during TC
and MC. TC and MC significantly reduced the retentive strength of the CAD/CAM
resin-based crowns whereas that of the CAD/CAM ceramic crowns was only affected
by TC. In addition, the resin-based crowns showed a higher number of crown
loosening during TC than the ceramic crowns. Analyses of CTE and E-modulus
indicated that the resin-based crowns would be more deformed during TC and MC
than the ceramic crowns. The present study demonstrated that the resistance of
crowns to microscale expansion and contraction caused by thermal and mechanical
fatigue would play an important role in maintaining retentive strength.
PMID- 29960249
TI - Experimental and analytical evaluation on the mass transfer performance of
braided stent-grafts.
AB - Endoleak and luminal loss related to blood permeation and microthrombus migration
remain the main challenges in the aneurysm treatment, although stent-grafts have
been widely applied. Stent-grafts provide a boundary to shield blood and
microemboli transport, which are correlated with their mass transfer performance.
Water permeability of vascular prostheses with woven and knitted structures has
been analyzed and documented by many researchers, as well as oxygen and protein
transfer. However, it is almost a total lack of blood and microemboli transfer
along the braided stent-graft thickness direction. In this research, we provided
a methodology for the vascular prostheses mass transfer evaluation. Braided stent
grafts in our former research were conducted on a self-developed testing system
to investigate their blood permeability and microthrombus transfer behaviors. The
pressure along wall thickness direction can be changed. Analytical models were
also established based on pore parameters, making them applicative to different
structures. Results revealed that the mass transfer behavior of stent-grafts was
positively affected by porosity and pore diameter while negatively influenced by
their thickness.
PMID- 29960250
TI - Simultaneous determination of nine anticoagulant rodenticides by ultra
performance liquid chromatography-tandem mass spectrometry with ultrasound
assisted low-density solvent dispersive liquid-liquid microextraction.
AB - A sensitive determination method is developed for nine anticoagulant rodenticides
(ARs) in urine samples by ultra-performance liquid chromatography-tandem mass
spectrometry (UPLC-MS/MS) with ultrasound-assisted low-density solvent dispersive
liquid-liquid microextraction (UA-LDS-DLLME) pretreatment. The target analytes
are brodifacoum, bromadiolone, warfarin, coumachlor, coumatetralyl, difenacoum,
pindone, diphacinone and chlorophacinone. The parameters that influence the
extraction recovery in the UA-LDS-DLLME were systematically investigated and
optimized. With the optimized extraction parameters, recoveries ranging from
64.6%-124.2% were obtained for the target analytes. The linear range for all
analytes was 0.1-100 ng/mL with correlation coefficients higher than 0.99. Very
low LODs ranging in 0.003-0.03 ng/mL were obtained. LOQs were in the range of
0.01-0.1 ng/mL for the nine target analytes. The accuracy that was expressed as
mean relative error was within +/-5.8% while the precision expressed as relative
standard error was less than 5.9%. The combination of UA-LDS-DLLME with UPLC
MS/MS is a feasible, sensitive and rapid analytical approach for the
determination of ARs in urine matrix, which is particularly suitable for clinical
and forensic purposes.
PMID- 29960251
TI - An effective and high-throughput analytical methodology for pesticide screening
in human urine by disposable pipette extraction and gas chromatography - mass
spectrometry.
AB - In this paper, the use of disposable pipette extraction (DPX) for the
determination of pesticides in human urine in possible cases of poisoning is
proposed for the first time. The pesticides studied were oxamyl, propoxur,
carbofuran, 3-hydroxycarbofuran, carbaryl, methiocarb, terbufos, parathion
methyl, malathion, chlorpyrifos and endosulfan. The pipette tip used for the
extraction of these compounds was commercially acquired. It has a capacity of 5
mL and contains 20 mg of sorbent material (styrene-divinylbenzene). The
optimization of the main parameters that can influence the extraction efficiency
of this sample preparation technique was performed with univariate and
multivariate approaches. The analytes were separated and identified by gas
chromatography coupled to mass spectrometry (GC-MS). The optimal extraction
conditions were 5 extraction cycles of 30 s and 5 desorption cycles of 15 s with
250 MUL of ethyl acetate. Elution of the extract was performed in a vial
containing 100 mg of anhydrous sodium sulfate. The method developed was
validated, providing correlation coefficients higher than 0.9955 for all
analytes, limits of detection (LOD) of 0.76 to 1.52 MUg L-1, limits of
quantification (LOQ) of 2.5 to 5.0 MUg L-1, relative recoveries of 63 to 118%,
intra-day precision of 0.7 to 15.3% and inter-day precision of 4.9 to 13.1%. An
effective and rapid method for the analysis of human urine for the identification
of possible cases of poisoning by pesticides was successful developed.
PMID- 29960252
TI - Cytomegalovirus-associated splanchnic vein thrombosis in immunocompetent
patients: A systematic review.
AB - INTRODUCTION: Venous thromboembolic events (VTE) occur in more than 5% of
hospitalized patients with acute CMV infection. In immunocompetent patients,
splanchnic vein thrombosis (SVT) and splenic infarction have been suggested to
represent approximately half of the published cases of CMV-associated VTE. We
performed a systematic review of the literature with the aim to describe
epidemiology, clinical characteristics, treatment, and natural history of CMV
associated SVT in immunocompetent patients. METHODS: Studies were identified by a
PubMed and Google Scholar electronic database search until January 2018. All
published papers describing immunocompetent adults with SVT occurring
concomitantly to an acute CMV infection were included. RESULTS: Forty-four
patients with CMV-associated SVT were described in 38 papers. Twenty-three
patients were male, mean age was 38.1 years (range, 17-68). Symptomatic SVT
occurred in 31 patients, incidental SVT in 13 patients. In symptomatic SVT, an
acute and severe onset with small bowel or splenic infarction required surgical
treatment for resolution in 22.6% of cases. Anticoagulation induced both a
favourable clinical outcome and a recanalization of SVT in more than 70% of the
remaining cases. In incidental SVT, a favourable clinical outcome and a complete
recanalization of SVT by anticoagulation were reported in more than 80% of cases.
No patient with CMV-associated SVT died and no SVT recurrence was reported.
CONCLUSIONS: CMV-associated SVT has probably a favourable clinical course in most
patients. Only future, well-designed, prospective studies with an adequate follow
up will allow to confirm the data of published cases.
PMID- 29960254
TI - Dual function of the boron center of BH(CO)2/BH(N2)2 in halogen- and triel-bonded
complexes with hypervalent halogens.
AB - The complexes between BH(CO)2/BH(N2)2 and XF3/XF5 are stabilized by a halogen
bond and a triel bond. The MEP analyses of BH(CO)2/BH(N2)2 indicate that there
are both a region with negative MEPs on the B atom in the vertical direction of
the molecular plane and a sigma-hole at the B-H bond end. Therefore, the boron
atom in BH(CO)2/BH(N2)2 plays a dual role of a Lewis base and an acid in the
halogen bond and triel bond, respectively. The halogen and triel bonds are
stronger in order of IF3< BrF3< ClF3, IF5< BrF5< ClF5, and BH(CO)2< BH(N2)2 in
most complexes. These complexes have large stability since the interaction energy
varies from -5 to -115 kcal/mol. The halogen bond belongs to a covalent
interaction or a partially covalent interaction in most complexes. The subsystems
in these complexes have prominent deformation, accompanied with big charge
transfer and large polarization.
PMID- 29960253
TI - Tracing natural and industrial contamination and lead isotopic compositions in an
Australian native bee species.
AB - This study investigates trace element concentrations (arsenic (As), manganese
(Mn), lead (Pb) and zinc (Zn)) and Pb isotopic compositions in an Australian
native bee species, Tetragonula carbonaria, and its products of honey and wax. Co
located soil and dust samples were simultaneously analysed with the objective of
determining if the bees or their products had potential application as a proxy
for monitoring environmental contamination. The most significant relationships
were found between Pb concentrations in honey (r = 0.814, p = 0.014) and wax (r =
0.883, p = 0.004) and those in co-located dust samples. In addition, Zn
concentrations in honey and soil were significantly associated (r = 0.709, p =
0.049). Lead isotopic compositions of native bee products collected from
background sites adjacent to Sydney national parks (206Pb/207Pb = 1.144,
208Pb/207Pb = 2.437) corresponded to local geogenic rock and soil values
(206Pb/207Pb = 1.123-1.176, 208Pb/207Pb = 2.413-2.500). By contrast, inner Sydney
metropolitan samples, including native bees and wax (206Pb/207Pb = 1.072-1.121,
208Pb/207Pb = 2.348-2.409), co-located soil and dust (206Pb/207Pb = 1.090-1.122,
208Pb/207Pb = 2.368-2.403), corresponded most closely to aerosols collected
during the period of leaded petrol use (206Pb/207Pb = 1.067-1.148, 208Pb/207Pb =
2.341-2.410). A large range of Pb isotopic compositions in beehive samples
suggests that other legacy sources, such as Pb-based paints and industrials, may
have also contributed to Pb contamination in beehive samples. Native bee data
were compared to corresponding samples from the more common European honey bee
(Apis mellifera). Although Pb isotopic compositions were similar in both species,
significant differences in trace element concentrations were evident across the
trace element suite, the bees and their products. The statistical association
between T. carbonaria and co-located environmental contaminant concentrations
were stronger than those in European honey bees, which may be attributable to its
smaller foraging distance (0.3-0.7 km versus 5-9 km, respectively). This implies
that T. carbonaria may be more suitable for assessing small spatial scale
variations of trace element concentrations than European honey bees.
PMID- 29960255
TI - Targeting a hidden site on class A beta-lactamases.
AB - Increasing resistance against available orthosteric beta-lactamase inhibitors
necessitates the search for novel and powerful inhibitor molecules. In this
respect, allosteric inhibitors serve as attractive alternatives. Here, we examine
the structural basis of inhibition in a hidden, druggable pocket in TEM-1 beta
lactamase. Based on crystallographic evidence that 6-cyclohexyl-1-hexyl-beta-D
maltoside (CYMAL-6) binds to this site, first we determined the kinetic mechanism
of inhibition by CYMAL-6. Activity measurements with CYMAL-6 showed that it
competitively inhibits the wild type enzyme. Interestingly, it exhibits a steep
dose-response curve with an IC50 of 100 MUM. The IC50 value changes neither with
different enzyme concentration nor with incubation of the enzyme with the
inhibitor, showing that inhibition is not aggregation-based. The presence of the
same concentrations of CYMAL-6 does not influence the activity of lactate
dehydrogenase, further confirming the specificity of CYMAL-6 for TEM-1 beta
lactamase. Then, we identified compounds with high affinity to this allosteric
site by virtual screening using Glide and Schrodinger Suite. Virtual screening
performed with 500,000 drug like compounds from the ZINC database showed that top
scoring compounds interact with the hydrophobic pocket that forms between H10 and
H11 helices and with the catalytically important Arg244 residue through pi-cation
interactions. Discovery of novel chemical scaffolds that target this allosteric
site will pave the way for a new avenue in the design of new antimicrobials.
PMID- 29960256
TI - Anti-inflammatory and antiproliferative diterpenoids from Plectranthus
scutellarioides.
AB - Chemical investigation of the dichloromethane extract of the aerial parts of
Plectranthus scutellarioides led to the isolation and characterization of 10
diterpenoids with an abietane skeleton and one cembrane-type diterpenoid. Among
them, six have not yet been described in the literature. Their structures were
established by 1D and 2D NMR, UV and IR spectroscopy, and HRESIMS. The relative
configuration was determined by Gauge-Independent Atomic Orbital NMR chemical
shift calculations supported by the advanced statistical method DP4 plus and
further confirmed by electronic circular dichroism. The isolated constituents
were evaluated for their in vitro NF-kappaB inhibitory activity, as well as for
their cytotoxic effects in human multiple myeloma cancer stem cells and RPMI 8226
tumor cell line. Coleon O, coleon G, lanugone K and 6-acetylfredericone B showed
the highest inhibitory effect against NF-kappaB, displaying IC50 of 11.2, 11.0,
4.5 and 9.7 MUM, respectively. Coleon O exhibited also a significant activity
towards human multiple myeloma cancer stem cells and RPMI 8226 cells with IC50 of
9.2 and 8.4 MUM, respectively.
PMID- 29960257
TI - A fast and reliable method for quantitation of THC and its 2 main metabolites in
whole blood by GC-MS/MS (TQD).
AB - An analytical method was developed for the simultaneous determination of Delta9-
tetrahydrocannabinol (THC), 11-hydroxy-Delta9-tetrahydrocannabinol (11-OH-THC)
and l1-nor-9-carboxy-Delta9-tetrahydrocannabinol (THC-COOH) in whole blood
samples, for identification and quantitation purposes. Samples were prepared
using solid-phase extraction, followed by gas chromatography/tandem mass
spectrometry (GC-MS/MS) analysis in multiple reaction monitoring mode, with a
total run time of 7.6min. MS/MS detection was achieved with two ion transitions
per substance. The method was fully validated, including selectivity and capacity
of identification, limit of detection and limit of quantitation, recovery,
carryover, linearity (1-100ng/mL), intra-assay precision, inter-assay accuracy.
The obtained results allowed its use in routine forensic analysis, with the
application to real samples, both clinical and post-mortem.
PMID- 29960258
TI - Ecological aspects of unusual findings of animals nesting inside a mummified
human corpse in natural conditions.
AB - We report, for the first time, a case of nesting by Apis mellifera mellifera (L.,
1758) (Insecta: Hymenoptera: Apidae), Vespula vulgaris (L., 1758) (Insecta:
Hymenoptera: Vespidae), and Sciurus vulgaris L., 1758 (Mammalia: Rodentia:
Sciuridae) inside a mummified human corpse in natural conditions (Lower Silesia
province, south-western Poland). A case history, autopsy findings, and biological
observations are provided. A list of the insect species found in the corpse is
provided and compared with available data. Other zoological findings are
mentioned and briefly discussed.
PMID- 29960259
TI - Impact of the electron beam on the thermal stability of gold nanorods studied by
environmental transmission electron microscopy.
AB - In-situ transmission electron microscopy experiments are of great interest to
nanoscience and nanotechnology. However, it is known that the electron beam can
have a significant impact on the structure of the sample which makes it important
to carefully interpret in-situ data. In this work, we studied the thermal
stability of CTAB-stabilized gold nanorods under different gaseous environments
in an environmental transmission electron microscope and compared the outcome to
ex-situ heating experiments. We observed a remarkable influence of the electron
beam: While the nanorods were stable under inert conditions when exposed to the
electron beam even at 400 degrees C, the same nanorods reshaped at temperatures
as low as 100 degrees C under ex-situ conditions. We ascribe the stabilizing
effect to the transformation of the CTAB bi-layer into a thin carbon layer under
electron beam irradiation, preventing the nanorods from deforming. When exposed
to an oxidizing environment in the environmental transmission electron
microscope, this carbon layer was gradually removed and the gold atoms became
mobile allowing for the deformation of the rod. This work highlights the
importance of understanding the phenomena taking place under electron beam
irradiation, which can greatly affect in-situ experiments and conclusions drawn
from these. It stresses that in-situ electron microscopy data, taken on measuring
the temperature dependence of nanoparticle properties, should be carefully
assessed and accompanied by ex-situ experiments if possible.
PMID- 29960260
TI - Association of lifestyle-related factors and psychological factors on quality of
life in people with schizophrenia.
AB - In people with schizophrenia several factors are associated with poor quality of
life (QoL), namely, lifestyle-related factors and psychological factors. However,
there has been little research on the impact of these factors on QoL. Therefore,
the relation between lifestyle-related factors, psychological factors, and QoL in
people with schizophrenia was assessed. A cross-sectional study was conducted
among 115 patients (25% women, 50% inpatients). QoL was measured by World Health
Organisation Quality of Life- Brief Version. Lifestyle-related factors were
assessed, namely physical activity (International Physical Activity Questionnaire
Short Form), sleep quality (Pittsburgh Sleep Quality Index) and dietary intake
(Mediterranean Diet score). Psychological factors such as self-esteem (Rosenberg
Self-Esteem Scale) and autonomous motivation (Behavioural Regulation
Questionnaire- version 3) were also measured. Regression analyses were performed
to identify significant predictors of QoL. Results showed that self-esteem
predicted better global, physical, psychological and environmental QoL. Physical
activity predicted better global and physical QoL, while sedentary time predicted
poor social and environmental QoL. Identifying predictors of QoL has implication
for the effective design and delivery of lifestyles interventions, including
physical activity, dietary education and smoking cessation in people with
schizophrenia. Adopting healthy lifestyles may lead to improved physical health,
psychological well-being and QoL in this population.
PMID- 29960261
TI - Understanding mental health among military veterans in the fire service.
AB - Firefighters who have previously served in the military may be at potentially
higher risk for worsened mental health outcomes. This investigation examined the
mental health of military veterans, as compared to non-veterans, in the fire
service. We hypothesized that firefighters who endorsed military veteran status
would have higher rates of mental health symptoms, in comparison to firefighters
who did not endorse prior service in the military. Age, gender, and
race/ethnicity were used as covariates. The sample was comprised of 910 career
firefighters, 209 (23.0%) of whom endorsed military veteran status. One-way
analyses of covariance were employed. The military veteran subsample reported
significantly higher levels of sleep disturbance, depression, and posttraumatic
stress symptom severity in comparison to the non-veteran subsample; however,
effect sizes were small indicating that between group differences are actually
negligible. Results highlight the need to improve our understanding of risk and
resilience factors for firefighters who have served in the military, as this line
of inquiry has potentially important mental health intervention implications for
this exceptionally understudied population.
PMID- 29960262
TI - Fine particulate matter constituents and stress hormones in the hypothalamus
pituitary-adrenal axis.
AB - Fine particulate matter (PM2.5) has recently been associated with the activation
of the hypothalamus-pituitary-adrenal (HPA) axis, increasing cardiometabolic
risks. However, it is unknown which constituents of PM2.5 were mainly responsible
for these associations. In a longitudinal panel study with 4 repeated
measurements among 43 college students in Shanghai, China, we measured serum
levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone
(ACTH) and cortisol, as indicators of HPA axis activation. Then, we evaluated the
associations of 22 constituents of PM2.5 with these stress hormones using linear
mixed-effect models. During the study period, the average daily concentration of
PM2.5 was 41.1 MUg/m3. We found that short-term exposure to PM2.5 was associated
with elevated levels of the 3 stress hormones. We observed that water-soluble
inorganic ions, especially nitrate (NO3-) and ammonium, had stronger influences
on 3 hormones. Six metallic elements, including Zn, Mn, Cu, Fe, Br, and Cr, had
positive but generally instable associations with 3 hormones. The effects of
organic carbon and elemental carbon on hormones were generally weak. When
correcting for multiple comparisons using false discovery rate, NO3- was still
significantly associated with CRH, but other important associations turned to be
insignificant. An interquartile range increase in NO3- on the previous day were
associated with 12.13% increase (95% confidence interval: 4.45%, 20.37%) in CRH.
Our findings suggested that water-soluble inorganic constituents of PM2.5
(especially, NO3-) might have stronger influences on the activation of HPA axis
than carbonaceous and elemental components.
PMID- 29960263
TI - The effect of medication on vastus lateralis muscle activation patterns in
Parkinson's disease patients.
AB - The effect of levodopa on muscle activity patterns in Parkinson's disease (PD)
patients is currently unclear. The aim of the present study was to compare the
spatial distribution pattern of electromyographic activity during sustained
isometric contraction in PD patients during on- and off-medication periods using
multi-channel surface electromyography (SEMG). Ten female PD patients were
recruited for the present study. All patients performed a sustained isometric
knee extension at 10% maximum voluntary contraction task for 60 s. To evaluate
alterations in the spatial SEMG potential distribution, the coefficient of
variation (CV) of force, normalized root mean square (RMS), modified entropy, CV
of the RMS, and correlation coefficients were calculated at during contraction
task. The off-medication period exhibited more fluctuation during the contraction
task than those in the on-medication period. The off-medication period exhibited
less change in modified entropy, the CV of RMS, the correlation coefficient and
patterns of spatial SEMG distribution. These data demonstrated that the
heterogeneity and changes in the activation pattern are smaller in the off
medication period than in those in the on-medication period. These findings might
indicate that levodopa enhanced the activation of muscle action potentials during
force production.
PMID- 29960264
TI - Radionuclide observables of underwater nuclear explosive tests.
AB - There remain technical challenges for an On-site Inspection (OSI) in the high
seas environment, which gathers evidence of a violation of the Comprehensive
Nuclear-Test-Ban Treaty (CTBT). For terrestrial nuclear explosions, the
radionuclide observables are well defined and States Parties have chosen 17
particulate radionuclides that allow discrimination from other nuclear events.
However, an underwater nuclear explosion generates induced radionuclides from the
neutron activation of seawater, which has the potential to interfere with the
measurement of the radionuclide observables using gamma-spectrometry techniques.
To understand these effects the inventory of OSI relevant (6.0 * 1016 Bq) and
activation (1.6 * 1019 Bq) radionuclides has been calculated for a 1 kT
underwater nuclear explosion. The activation products consist predominantly of
38Cl and 24Na, which decay to 5.56% and 0.0007% of their initial activity within
1 and 14 days. Monte Carlo techniques have been used to assess spectral
interferences within this timeframe. It is demonstrated that during this period
they do not interfere with the measurement of the existing radionuclide
observables. Additionally, 24Na has been identified as useful for inspection
purposes.
PMID- 29960265
TI - Feasibility of a low-dose orbital CT protocol with a knowledge-based iterative
model reconstruction algorithm for evaluating Graves' orbitopathy.
AB - PURPOSE: To evaluate the clinical feasibility of low-dose orbital CT with a
knowledge-based iterative model reconstruction (IMR) algorithm for evaluating
Graves' orbitopathy. METHODS: Low-dose orbital CT was performed with a CTDIvol of
4.4 mGy. In 12 patients for whom prior or subsequent non-low-dose orbital CT data
obtained within 12 months were available, background noise, SNR, and CNR were
compared for images generated using filtered back projection (FBP), hybrid
iterative reconstruction (iDose4), and IMR and non-low-dose CT images. Comparison
of clinically relevant measurements for Graves' orbitopathy, such as rectus
muscle thickness and retrobulbar fat area, was performed in a subset of 6
patients who underwent CT for causes other than Graves' orbitopathy, by using the
Wilcoxon signed-rank test. RESULTS: The lens dose estimated from skin dosimetry
on a phantom was 4.13 mGy, which was on average 59.34% lower than that of the non
low-dose protocols. Image quality in terms of background noise, SNR, and CNR was
the best for IMR, followed by non-low-dose CT, iDose4, and FBP, in descending
order. A comparison of clinically relevant measurements revealed no significant
difference in the retrobulbar fat area and the inferior and medial rectus muscle
thicknesses between the low-dose and non-low-dose CT images. CONCLUSIONS: Low
dose CT with IMR may be performed without significantly affecting the measurement
of prognostic parameters for Graves' orbitopathy while lowering the lens dose and
image noise.
PMID- 29960266
TI - Cross sectional imaging of pulmonary fibrosis translating pathology into
radiology.
AB - There are three major pathologic patterns of pulmonary fibrosis; usual
interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and
airway-centered fibrosis (ACF). These pathologic patterns correspond with
radiographic patterns of UIP, NSIP, and chronic hypersensitivity pneumonitis
(CHP). Previous studies have demonstrated that the radiologic diagnosis is
correct approximately 50% of the time for these fibrotic lung diseases.
Understanding the microscopic pathologic patterns that are recapitulated at a
macroscopic level in the high resolution CT scan is key to radiologists' ability
to correctly diagnose pulmonary fibrosis and thus improve patient outcomes with
early diagnosis and avoidance of biopsy. We investigate the similarities between
the pathology and radiology features of UIP, NSIP, and ACF.
PMID- 29960267
TI - Acute eosinophilic appendicitis: a radiologic-pathologic correlation.
AB - Inflammation of the appendix is one of the most common conditions requiring
emergent surgical intervention. Computed tomography commonly demonstrates a
dilated appendix with adjacent inflammation. Traditionally, luminal obstruction
of the appendix has been thought to be the primary etiology of appendicitis.
However, current evidence suggests that etiology of appendicitis is
multifactorial and can involve a number of different pathogenic pathways. Here we
present a case of acute eosinophilic appendicitis with radiologic-pathologic
correlation from a hypersensitivity reaction pathway. Acute eosinophilic
appendicitis may represent an early precursor to conventional acute suppurative
(phlegmonous) appendicitis, or a variant form of acute appendicitis.
PMID- 29960268
TI - Modelling of magnetoimpedance response of thin film sensitive element in the
presence of ferrogel: Next step toward development of biosensor for in-tissue
embedded magnetic nanoparticles detection.
AB - In-tissue embedded magnetic nanoparticle (MNPs) detection is one of the most
interesting cases for cancer research. In order to understand the origin, the
limits and the way of improvement of magnetic biosensor sensitivity for the
detection of 3D mezoscopic distributions of MNPs, we have developed a
magnetoimpedance biosensor prototype with a [Cu (3 nm)/FeNi(100 nm)]5/Cu(500
nm)/[FeNi(100 nm)/Cu(3 nm)]5 rectangular sensitive element. Magnetoimpedance (MI)
responses were measured with and without polyacrylamide ferrogel layer mimicking
natural tissue in order to evaluate stray fields of embedded MNPs of gamma-Fe2O3
iron oxide. A model for MI response based on a solution of Maxwell equations with
Landau-Lifshitz equation was developed in order to understand the origin of the
prototype sensitivity which reached 1.3% of DeltaZ/Z per 1% of MNPs concentration
by weight. To make this promising technique useful for magnetically labeled
tissue detection, a synthesis of composite gels with MNPs agglomerates compactly
located inside pure gel and their MI testing are still necessary.
PMID- 29960269
TI - Biosensors for determination of D and L- amino acids: A review.
AB - Amino acids (AAs) of nutritional importance exist as L-isomers, while D-isomeric
form of AAs is common constituent of bacterial cell wall. The presence of D-amino
acids in foods is promoted by harsh technological processes (e.g., high
temperature, extreme pH, adulteration or microbial contamination). The detection
of free AAs in different brain disorders is also very important. Among the
various methods available for detection of AAs, most are complicated and require
time-consuming sample pre-treatment, expensive instrumental set-up and trained
persons to operate, specifically for chromatographic methods. The biosensing
methods overcome these drawbacks, as these are simple, fast, specific and highly
sensitive and can also be applied for detection of AAs in vivo. This review
presents the principles, merits and demerits of various analytical methods for AA
determination with special emphasis on D-amino acids (DAA) and L-amino acids
(LAA) biosensors. The electrochemical AA biosensors work optimally within 2-900
s, pH range, 5.3-9.5; temperature range, 25-45 degrees C; AA concentration
range, 0.0008-8000 mM, limit of detection(LOD) between 0.02 and 1250 uM and
working potential from -0.05 to 0.45 V. These biosensors measured AA level in
fruit juices, beverages, urine, sera and were reused 200 times over a period of 7
120 days. The use of various nanostructures and electrochemical microfluidic
paper based analytical device (EMUPAD) are suggested for further development of
AA biosensors.
PMID- 29960270
TI - Highly sensitive paper-based immunoassay using photothermal laser speckle
imaging.
AB - Paper-based lateral-flow assay (LFA) is a simple and inexpensive point-of-care
device that has become commonplace in medicine, environmental monitoring, and
over-the-counter personal use. Some LFAs have demonstrated comparable analytical
performance with laboratory-based methods, but the detection limit or sensitivity
of most LFAs is significantly inferior to other molecular techniques by 10-100 *
. Consequently, LFAs are not viable for the early detection of disease-relevant
biomarkers that are present in extremely small amounts in clinical specimens.
Herein, we present a simple, cost-effective, and highly sensitive LFA sensor
based on photothermal laser speckle imaging (PT-LSI). Under the illumination of a
photothermal excitation light, gold nanoparticles (AuNPs), a common signal
transduction medium in LFAs, absorb the light energy to produce heat, which
subsequently induces modulation of the optical property and thermal deformation
of the membrane. We measured these fluctuations through laser speckle imaging to
quantify the concentration of AuNP-biomarker complexes. We experimentally
demonstrate that the detection limit of our technique is superior to that of
colorimetric detector by 68-125 * . The capability of our sensor for highly
sensitive detection of disease biomarkers is validated by using U.S. FDA-approved
LFA kits for cryptococcal antigens (CrAg).
PMID- 29960271
TI - RuO2/graphene nanoribbon composite supported on screen printed electrode with
enhanced electrocatalytic performances toward ethanol and NADH biosensing.
AB - In this work, we aimed to propose a newly synthesized composite material with
enhanced electrocatalytic properties as a novel screen-printed sensor for the
quantification of NADH. Additionally, the surface was modified with alcohol
dehydrogenase for the preparation of an amperometric biosensor for analysis of
ethanol. Synthesized material was characterized using several microstructural (FE
SEM, HR-TEM, XRD) and electrochemical (CV, EIS) techniques. The electrochemical
response of the tested analytes was investigated as a function of important
parameters. Under optimal conditions, the working linear range and limit of
detection for ethanol sensing was 1-1800 uM and 0.19 uM, respectively. For NADH,
the linear range was from 1 to 1300 uM with limit of detection of 0.52 uM.
Moreover, effects of some possible interfering compounds were investigated and
the developed procedure was applied to commercial alcoholic beverages. The
results obtained showed satisfactory precision and accuracy of the developed
method and confirm the proposed approach could be a possible replacement for the
currently used techniques for ethanol and NADH quantification.
PMID- 29960272
TI - Deletion of Extra Domain A of Fibronectin Reduces Acute Myocardial
Ischaemia/Reperfusion Injury in Hyperlipidaemic Mice by Limiting Thrombo
Inflammation.
AB - BACKGROUND: Fibronectin splicing variant containing extra domain A (Fn-EDA),
which is an endogenous ligand for Toll-like receptor 4 (TLR4), is present in
negligible amounts in the plasma of healthy humans, but markedly elevated in
patients with co-morbid conditions including diabetes and hyperlipidaemia, which
are risk factors for myocardial infarction (MI). Very little is known about the
role of Fn-EDA in the pathophysiology of acute MI under these co-morbid
conditions. MATERIALS AND METHODS: We determined the role of Fn-EDA in
myocardial ischaemia/reperfusion (I/R) injury in the hyperlipidaemic
apolipoprotein E-deficient (ApoE-/-) mice. Infarct size, plasma cardiac troponin
I (cTnI) levels, intravascular thrombosis (CD41-positive), neutrophil
infiltration (Ly6 B.2-positive), neutrophil extracellular traps (citrullinated H3
positive) and myocyte apoptosis (terminal deoxynucleotidyl transferase-mediated
dUTP nick-end labelling-positive) were assessed in myocardial I/R injury model (1
hour ischaemia/23 hours of reperfusion). RESULTS: Irrespective of gender, Fn-EDA
/-ApoE-/- mice exhibited smaller infarct size and decreased cTnI levels
concomitant with reduced post-ischaemic intra-vascular thrombi, neutrophils
influx, neutrophil extracellular traps and myocyte apoptosis (p < 0.05 vs. ApoE-/
mice). Genetic deletion of TLR4 attenuated myocardial I/R injury in ApoE-/- mice
(p < 0.05 vs. ApoE-/- mice), but did not further reduce in Fn-EDA-/- ApoE-/- mice
suggesting that Fn-EDA requires TLR4 to mediate myocardial I/R injury. Bone
marrow transplantation experiments revealed that Fn-EDA exacerbates myocardial
I/R injury through TLR4 expressed on the haematopoietic cells. Infusion of a
specific inhibitor of Fn-EDA, 15 minutes post-reperfusion, into ApoE-/- mice
attenuated myocardial I/R injury. CONCLUSION: Fn-EDA exacerbates TLR4-dependent
myocardial I/R injury by promoting post-ischaemic thrombo-inflammatory response.
Targeting Fn-EDA may reduce cardiac damage following coronary artery re
canalization after acute MI.
PMID- 29960273
TI - Haematopoietic Stem Cell Transplantation in Children Shifts the Coagulation
System towards a Pro-Coagulant State.
AB - Coagulation system is disturbed by several mechanisms after allogeneic
haematopoietic stem cell transplantation (HSCT). We evaluated the effect of HSCT
on coagulation system by various conventional and investigational methods in 30
children and adolescents who received HSCT due to haematological malignancies.
Pro-thrombin fragment 1 + 2, a specific measure of thrombin generation, and von
Willebrand factor, a measure of endothelial activation, increased after
conditioning treatment, and remained elevated until 3 months after HSCT (p < 0.05
for all comparisons to pre-conditioning treatment). D-dimer, a measure of fibrin
turnover, was elevated from the second week onwards until 4 weeks after HSCT (p <
0.05). Endogenous thrombin potential was increased after conditioning, and at 2
weeks after HSCT (p < 0.05). Furthermore, the activities of acute phase reactants
fibrinogen and coagulation factor VIII were increased (p < 0.05 for all
comparisons to pre-conditioning treatment) from the first week onwards up to 3
weeks and 3 months after HSCT, respectively. Taken together, paediatric patients
receiving HSCT demonstrate distinct and prolonged variations in the coagulation
system towards a pro-coagulant state. This shift is of importance when estimating
the risk of haemostatic and thrombotic complications in these children.
PMID- 29960274
TI - Rivaroxaban and Apixaban Anti-Xa Measurements: Impact of Plasma Storage for 7
Days at Room Temperature.
PMID- 29960275
TI - Novel Immunoassay for Complement Activation by PF4/Heparin Complexes.
PMID- 29960276
TI - Derivation and Validation of a Prediction Model for Risk Stratification of Post
Thrombotic Syndrome in Elderly Patients with a First Deep Vein Thrombosis.
AB - BACKGROUND: Not all patients carry the same risk of developing a post-thrombotic
syndrome (PTS), we therefore aimed to derive a prediction rule for risk
stratification of PTS in patients with deep vein thrombosis (DVT). METHODS: Our
derivation sample included 276 patients with a first acute symptomatic lower limb
DVT enrolled in a prospective cohort. We derived our prediction rule using
regression analysis, with the occurrence of PTS within 24 months of a DVT based
on the Villalta score as outcome, and 11 candidate variables as predictors. We
used bootstrapping methods for internal validation. RESULTS: Overall, 161
patients (58.3%) developed a PTS within 24 months of a DVT. Our prediction rule
was based on five predictors (age >= 75 years, prior varicose vein surgery, multi
level thrombosis, concomitant antiplatelet/non-steroidal anti-inflammatory drug
therapy and the number of leg symptoms and signs). Overall, 16.3, 31.2 and 52.5%
of patients were classified as low- (score, 0-3), moderate (score, 4-5) and high
risk (score, >= 6), for developing a PTS. Within 24 months of the index DVT,
24.4% of the patients in the low-risk category developed a PTS, 38.4% in the
moderate and 80.7% in the high-risk category. The prediction model showed good
predictive accuracy (area under the curve, 0.77; 95% confidence interval, 0.71
0.82, calibration slope, 0.90 and Brier score, 0.20). CONCLUSION: This easy-to
use clinical prediction rule accurately identifies patients with DVT who are at
high risk of developing PTS within 24 months who could potentially benefit from
special educational or therapeutic measures to limit the risk of PTS.
PMID- 29960277
TI - Is a normal chest radiograph sufficient to exclude pulmonary abnormalities
potentially associated with chronic cough?
AB - INTRODUCTION: There are few original studies on the true role of normal chest
radiograph (CXR) in exclusion of pulmonary conditions that may be associated with
chronic cough. Thus, the aim of the study was to assess whether a plain CXR is a
sufficient tool to exclude relevant pulmonary causes of chronic cough. MATERIAL
AND METHODS: A retrospective analysis of chest computed tomography (CT) scans in
non-smoking patients with chronic cough and normal CXR was performed. The
percentage of individuals in whom chest CT revealed relevant abnormalities was
compared with the percentage of patients with irrelevant findings or normal chest
CT scans. The negative predictive value (NPV) of the CXR in diagnosing the causes
of chronic cough was calculated as a proportion of true negative CXRs (normal CXR
AND irrelevant CT findings OR normal CT scan) to all negative CXRs (all patients,
who had both a CXR and CT scan). RESULTS: The study group consisted of 59 adult
patients with chronic cough, normal CXR and CT scan performed to diagnose the
cause of chronic cough. In 21 patients (21/59, 36%), chest CT revealed
abnormalities that were classified as relevant to chronic cough. The most
frequent were: bronchiectasis (7/59, 11.9%), bronchial wall thickening (6/59,
10.2%) and mediastinal lymphadenopathy (5/59, 8.5%). The NPV of a CXR in
diagnosing the causes of chronic cough was 64%. CONCLUSIONS: In conclusion, the
NPV of CXR in diagnosing pulmonary causes of chronic cough is relatively low.
Thus, plain CXR seems to be insufficient to exclude pulmonary diseases
potentially associated with chronic cough.
PMID- 29960278
TI - Pulmonary tuberculosis in a male with silicosis.
AB - Silicosis, a preventable occupational lung disease, is associated with various
diseases, including tuberculosis (TB). There is an increased lifelong risk for
lung tuberculosis even if exposure to silica dust ceases. That association
contributes in a large extent to very high rates of tuberculosis in countries
with poor TB and silica exposure control. We report a case of a male with a prior
diagnosis of silicosis who was diagnosed with and treated for TB. Anti
tuberculous treatment was extended due to a positive sputum smear in the six th
month of treatment. However, the culture of the sputum was negative. This case
report highlights the value of thorough screening for tuberculosis in silicotic
patients. The clinical management of these patients may be challenging due to
frequent overlapping radiological features and uncertain results of TB treatment.
PMID- 29960279
TI - Difficulties in the treatment of recurring diffuse alveolar hemorrhage
accompanying primary antiphospholipid syndrome: a case report and literature
review.
AB - Pulmonary embolism is the most common pulmonary manifestation of primary
antiphospholipid syndrome (PAPS). However, PAPS may manifest in the respiratory
system also due to non-thrombotic processes. In the following paper we present a
case of PAPS-related diffuse alveolar hemorrhage (DAH). Because of sparse
literature and a lack of randomized controlled trials, there are currently no
recommendations regarding the optimal choice of steroid-sparing agent in treating
PAPS-related DAH. In our patient, treatment with cyclophosphamide or
mycophenolate mofetil along with low dose prednisone was ineffective, partially
because of infectious complications, whereas addition of monthly intravenous
immunoglobulin to mycophenolate mofetil and prednisone, appears to control the
disease.
PMID- 29960280
TI - Pulmonary veno-occlusive disease: pathogenesis, risk factors, clinical features
and diagnostic algorithm - state of the art.
AB - Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary haemangiomatosis
(PCH) are rare disorders, with the estimated prevalence of less than 1 case per
million inhabitants. The vascular pathology in PVOD/PCH involves pre-septal and
septal veins, alveolar capillaries and small pulmonary arteries. According to the
ERS/ESC classification of pulmonary hypertension (PH) from 2015, PVOD/PCH have
been included in the subgroup 1' of pulmonary arterial hypertension (PAH). Recent
data indicate, however, the possibility of PVOD/PCH pathology in the patients
diagnosed in the group 1. The problem may concern PAH associated with
scleroderma, drug- induced PAH, PAH due to HIV infection and up to 10% of
patients with idiopathic PAH (IPAH). Recently, bi-allelic EIF2AK4 mutations were
found in the cases with heritable form of PVOD/PCH and in about 9% of sporadic
cases. Moreover, an association between occupational exposure to organic solvents
and PVOD/PCH was proved. The present review is an attempt to summarise the
current data on pathogenesis, risk factors, clinical features and diagnostic
algorithm for PVOD/PCH.
PMID- 29960281
TI - Immune checkpoint inhibitors in non-small cell lung cancer - towards daily
practice.
AB - Immunotherapy with immune checkpoint inhibitors (ICIs) revolutionized therapy of
solid tumors, among them- lung cancer. PD-1, PD-L1 blockers have been shown to
improve overall survival in advanced, metastatic non-small cell lung cancer. In
individual patients, 3-5-year survival has been achieved. Nivolumab,
pembrolizumab, atezolizumab are approved in lung cancer treatment. Practical
observations in reallife show that the results are comparable with those achieved
in clinical trials. The effects of ICIs depend on the patient performance status;
age, sex, histology; the presence of brain metastases have not modified treatment
results. ICIs therapy is safe and well tolerated; immune related adverse events
are observed. Pneumonitis may be a serious and fatal complication, but
glucocorticoids are usually curative. For proper patients selection for ICIs
treatment, the detection of PD-L1 expression on cancer cells is used. The so
called "hot" tumors with high expression of PD-L1 and abundant infiltration by
cytotoxic cells seem to better respond to treatment than "cold" tumors.
PMID- 29960282
TI - Recommendations for the management of tuberculosis in children - KOMPASS TB. Part
1: Tuberculosis prevention.
AB - Since the second half of the 20th century the incidence of tuberculosis has been
declining in Poland. Despite this, current epidemiological data still support the
need for the continued mass BCG vaccination in Poland in the near future. Apart
from the protection against severe hematogenous forms of tuberculosis,
vaccination lowers the risk of infection with Mycobacterium tuberculosis. Primary
and acquired immunodeficiency, including immunity disorders associated with an
ongoing treatment, are contraindications to BCG vaccination. The most common
adverse effects following BCG vaccination are reactions at the site of injection
and in regional lymph nodes, which usually does not require treatment. Methods of
tuberculosis prevention, particularly recommended in low-incidence countries,
include: diagnostic investigations of patients who had contacts with pulmonary
tuberculosis as well as an active detection and treatment of latent Mycobacterium
tuberculosis infection. Latent tuberculosis infection can be identified on the
basis of positive results of the tuberculin skin test or interferon-gamma release
assays after the active disease has been ruled out. This condition does require
prophylactic treatment.
PMID- 29960283
TI - Traditional medical uses of Drimia species in terms of phytochemistry,
pharmacology and toxicology.
AB - Drimia genus includes plants that used from ancient time for various ailments
such as dropsy, respiratoryailment, bone and joint complications, skin disorders,
epilepsy and cancer. Toxic propertiesof some Drimia species also were noted by
ancient scientists and these plants have been traditionallyused for rat control.
Bufadienolides have been identified as the main constituents in the genus
ofDrimia. Phenolics, sterols, protein and some of other phytochemicals have been
also isolated fromthese plants. Pharmacological and clinical studies have
strongly approved their effect on cardiovascularsystem. Extracts and compounds
isolated from Drimia species showed biological activities such asantibacterial,
antifungal, antiviral, antioxidant, anti-inflammatory and insecticidal effects
through several in vivo and in vitro studies. Moreover, cytotoxic and antitumor
activities which may be relatedto bufadienolide content of these plants have been
considered by many researchers. Traditional therapeuticvalues of these plants for
treating respiratory and rheumatic ailments as well as skin disordersare needed
to be validated through more researches. Toxic effects of these plants and
isolated compoundshave been investigated through several in vivo studies. Drimia
plants and their isolated compoundshave narrow therapeutic index, so patients
should be prohibited from applying these plantswithout medical supervision and
should be informed about the main intoxication symptoms beforestarting treatment.
Moreover, interaction of Drimia plants with other constituents of
traditionalherbal mixtures as well as chemical and biological modalities for
reducing toxicity of bufadienolidecompounds can be subjected for future studies.
PMID- 29960284
TI - Adherence reporting in clinical trials of type 2 Diabetes Metellius in the field
of Traditional Chinese Medicine.
AB - OBJECTIVE: To assess the medication adherence reporting in clinical trials the
field of Traditional ChineseMedicine (TCM) and the impact factors of medication
adherence. METHODS: Reviewed and evaluated were all randomized clinical trials in
the field of TCM in treatmentof type 2 diabetes mellitus published in Chinese
journals in 2012, in terms of their medicationadherence, adherence measurement,
and impacted factors of adherence. RESULTS: Finally 124 studies were included.
None studies reported the medication adherence. Thefactors impacting medication
adherence couldn'tbe analyzed due to none reporting adherence. CONCLUSION:
Medication adherence reporting was poor in clinical trials in TCM research.
Establishingstandards for adherence assessment and reporting may be one of the
important steps to improvethe quality of clinical studies.
PMID- 29960285
TI - Treatment of exfoliative cheilitis with Traditional Chinese Medicine: a
systematic review.
AB - OBJECTIVE: To systematically review treatments of exfoliative cheilitis based on
symptom patterns interms of Traditional Chinese Medicine. METHODS: PubMed,
Cochrane Central Register of Controlled Trials and Wanfang data were screenedfor
case reports, case series or clinical trials that were published in English or
Chinese from January,1973 to September, 2015. The keyword of "exfoliative
cheilitis or scaling cheilitis or factitious cheilitis"was used. Effectiveness or
ineffectiveness was investigated as outcome for Meta analysis, which isbased on
effective index in each study. Response to treatment was described for case
reports or caseseries. RESULTS: From 38 screened studies, 17 were randomized
controlled trials (RCTs), 5 were single-armtrials, and 16 were case reports or
case series. Three RCTs were eligible for Meta analysis and all of themcompared
managements between Traditional Chinese Medicine and corticosteroids for
exfoliativecheilitis, which involved 223 participants. Interestingly, data of
Meta analysis showed similar effect ofTraditional Chinese Medicine and
corticosteroids for patients with exfoliative cheilitis [relative risk
ratio:1.10; 95% CI (1.00-1.21), P = 0.06]. CONCLUSION: Traditional Chinese
Medicine might be a substitute for corticosteroids on exfoliativecheilitis.
However, the evidence and recommendation of exfoliative cheilitis managements
need tobe taken with caution because of the low quality of evidence in the
studies obtained.
PMID- 29960286
TI - Influence of clinical pathways used the hospitals of Traditional Chinese Medicine
on patients hospitalized with stroke: a systematic reviewand Meta-analysis.
AB - OBJECTIVE: To evaluate the influence of clinical pathways in the hospitals using
the Traditional ChineseMedicine in treatment of stroke in terms of postoperative
complications, length of stay (LOS),costs incurred during hospitalization,
compared with standard medical care. METHODS: Medline, Embase, China National
Knowledge Infrastructure (CNKI) platforms, Wanfangdatabases and the Cochrane
Central Register of Controlled Trials were searched. The search wasperformed up
to August 2014. Each study was assessed independently by two reviewers. The
assessmentof methodological quality of the included studies was based on the
Methodological index fornon-randomized studies standard. Meta-analyses were
performed using RevMan software, version5.0. RESULTS: Six studies met the study
inclusion criteria and were included in the Meta-analysis for a totalsample of
710 patients. The aggregate overall results showed that shorter length of stay in
the clinicalpathway group was observed during hospital stay was associated with
the use of the clinicalpathways. No significant differences were found in other
effects. CONCLUSION: Regardless the possible limitations, our findings show that
clinical pathways can significantlyreduce LOS. Although there is no clear
evidence that clinical pathways can reduce hospitalcosts, but the cost of
hospitalization path group for each included study were lower than the control
group.
PMID- 29960287
TI - Add-on effect of Qinbei Qingfei Yiqi granules for ventilator-associated pneumonia
in intensive care units: a randomized controlled trial.
AB - OBJECTIVE: To evaluate the add-on effect of Qinbei Qingfei Yiqi (QBQFYQ) granules
for ventilator-associatedpneumonia (VAP) in non-infectious critically ill
patients. METHODS: In this randomized controlled trial, 80 non-infectious
critically ill patients undergoing mechanicalventilation in the intensive care
unit (ICU) were randomly divided into two groups: those receivingQBQFYQ granules
plus usual treatment (experimental group, n = 50) and those receiving onlythe
usual treatment (control group, n = 30). The main outcome measures were VAP rate,
time of VAPoccurrence, duration of mechanical ventilation, and length of ICU
stay. Interleukin-6 (IL-6), C-reactiveprotein (CRP), and T-lymphocyte (CD4+,
CD8+, and CD4+/CD8+ ratio) serum levels were also evaluatedbefore and after
treatment. RESULTS: Compared with the control group treatment QBQFYQ
administration significantly reducedthe duration of mechanical ventilation [(9.58
+/- 3.14) vs (12.52 +/- 4.33) days] and length of ICUstay [(14.57 +/- 3.72) vs
(17.82 +/- 5.24) days] and delayed VAP occurrence [(4.31 +/- 0.86) vs (2.43 +/-
0.27)days]. Additionally, CRP and IL-6 serum levels and CD4+/CD8+ ratio were
significantly lower in the experimental group (P < 0.05) than in the control
group. However, there were no significant differencesin hospital mortality rate
(30.0% vs 33.3% ) and adverse events (4.0% vs 6.7%).adverse events (4.0% vs
6.7%). CONCLUSION: QBQFYQ delays the time of VAP occurrence and shortens the
duration of mechanicalventilation in non-infectious critically ill patients,
possibly through anti-inflammatory and immunomodulatorymechanisms.
PMID- 29960288
TI - Effect of Tiaoshen Kaiqiao acupuncture in the treatment of ischemic post-stroke
depression: a randomized controlled trial.
AB - OBJECTIVE: To observe the effect of Tiaoshen Kaiqiao acupuncture in the treatment
of ischemicpost-stroke depression. METHODS: This research was a single-blind,
positive-controlled trial done in a single entity. Totally58 patients with
ischemic post-stroke depression were randomly divided into two groups. The
acupuncturegroup was given Tiaoshen Kaiqiao acupuncture therapy and placebo
starch tablets treatment,while the control group was treated with fluoxetine
tablets and body acupuncture treatment.Evaluated the clinical efficacy of the two
groups with Hamilton Depression Scale (HAMD),Anti Depression Drug Side Effects
Rating Scale (SERS), Clinical Global Impression Scale (CGI) respectivelybefore
treatment, the fourth weekend of treatment, the eighth weekend of treatment, the
twelfth weekend of treatment. The adverse reactions in two groups were observed
and documented. RESULTS: The HAMD scale scores of the two groups in different
treatment period were significantlydecreased compared with that before treatment
(P < 0.05); the score reduction of HAMD scalebetween the two groups had no
significant differences (P > 0.05). There was significant difference betweenthe
SERS scores of two groups (P < 0.05); the control group had more adverse
reactions, and thescore would be increased with the extension of treatment time.
Effect index (EI) of CGI in the acupuncturegroup is better than that of control
group (P < 0.05). CONCLUSION: The effects of Tiaoshen Kaiqiao acupuncture and
fluoxetine in the treatment of ischemicpost-stroke depression were similar, but
the former had no obvious adverse reaction and side effects.
PMID- 29960289
TI - Effect of electroacupuncture on chemotherapy-induced peripheral neuropathy in
patients with malignant tumor: a single-blinded, randomizedcontrolled trial.
PMID- 29960290
TI - Efficacy and safety of Reduqing granules in the treatment of common cold with
wind-heat syndrome: a randomized, double-blind,double-dummy, positive-controlled
trial.
AB - OBJECTIVE: To assess the efficacy and safety of Reduqing granules in patients
with common coldwith wind-heat syndrome (CCWHS). METHODS: A randomized, double
blind, double-dummy, parallel, positive- controlled trial included72 CCWHS
patients was performed. The participants were randomly assigned to two
groups,Reduqing (RDQ) group and Lianhuaqingwen (LHQW) group, in a 1:1 ratio.
Patients in RDQ groupreceived Reduqing granules and dummy Lianhuaqingwen capsules
three times a day and patients inLHQW group received Lianhuaqingwen capsules and
dummy Reduqing granules three times daily.The duration of treatment and follow-up
were four days. RESULTS: There were no statistically significant differences in
total markedly effective rate and totaleffective rate between RDQ group and LHQW
group after treatment. Traditional Chinese Medicine(TCM) symptom score was
significantly reduced after treatment in RDQ group, as well as inLHQW group.
However, the difference of change in TCM symptom score between two groups was
notstatistically significant (P > 0.05). There were no significant differences
between two groups in the mediantime to fever relief [RDQ group (4 +/- 8) h vs
LHQW group (4 +/- 5) h] or the median time to feverclearance (RDQ group 47 h vs
LHQW 36 h). No serious adverse events were reported during the study. CONCLUSION:
Compared with Lianhuaqingwen capsules, Reduqing granules achieved similar
therapeuticeffect in the treatment of CCWHS and no drug-related adverse events
were reported duringthe study. Therefore, Reduqing granules might be effective
and safe in the treatment of CCWHS.
PMID- 29960291
TI - Evaluation of a granulated formula for the nerve root type and vertebral artery
type of cervical spondylosis: a multicenter, single-blind, randomized,
controlled, phase III clinical trial.
AB - OBJECTIVE: To evaluate the effectiveness and safety of cervical spondylosis
formula granules in reducingthe symptoms of patients with the nerve root type and
the vertebral artery type of cervical spondylosis. METHODS: This was a
multicenter, single-blind, randomized, controlled trial. From April 2002 to
November2003, 499 patients were randomly assigned to either the treatment or the
control group.The treatment group was orally administered granules prepared with
a formula for cervical spondylosis,while the control group was given Jingfukang
granules. The treatment course was 1 month for both groups. RESULTS: In patients
with the nerve root type of cervical spondylosis, the total effect rate in
thetreatment group (87.21% ) was significantly higher than that in the control
group (80.70%, P < 0.01). Afterthe treatment period in both groups, the treatment
group had a significantly greater rate of resolutionof pain, numbness of the
upper limbs, muscle strength of the upper limbs, and fatigue thanthe control
group (all P < 0.05). In patients with the vertebral artery type of cervical
spondylosis, the totaleffect rate in the treatment group (82.07%) was similar to
that in the control group (71.21% , P >0.05). After the treatment period in both
groups, the treatment group had a significantly greater rateof resolution of
weakness of the waist and knees than the control group (P < 0.05). CONCLUSION:
The cervical spondylosis formula granules significantly improve numbness,
musclestrength, and fatigue, and reduce pain in patients with the nerve root type
of cervical spondylosis,and improve the weakness of the waist and knees in
patients with the vertebral artery type of cervicalspondylosis.
PMID- 29960292
TI - Association between peroxisome proliferator-activated receptor gamma gene
polymorphism and susceptibility to northwest dryness syndrome.
AB - OBJECTIVE: To investigate the relationship between gene polymorphism of
peroxisome proliferator-activated receptor (PPAR) and susceptibility to northwest
dryness syndrome (NDS). METHODS: The polymorphisms of 11 PPARgamma gene loci
rs10510418, rs12633551, rs1373640,rs17036188, rs2921190, rs4135247, rs4135275,
rs4135283, rs6768587, rs709156, and rs7615916were detected in 249 patients with
NDS and 260 patients with non-NDS (control group) by usingSnapshot single
nucleotide polymorphism typing technology. RESULTS: All locus detections were in
accordance with Hardy-Weinberg equilibrium test. Comparedwith the control group,
rs2921190 genotype frequency showed statistical difference in the NDSgroup (P <
0.05). Two-two comparison result showed that CC genotype frequency in the
NDSgroup was higher than that in the control group. CT and TT genotype
distribution frequenciesshowed differences between the two groups. The rare
allele frequency in the NDS group was lowerthan that of the control group (P <
0.01). Multi-factor logistic regression analysis showed that the ageand genotype
entered the regression equation. The subjects in the age bracket 30-55 and 45-45
were1.796 and 1.561 times likely, respectively, than those in other age brackets
to contract NDS,. Thepatients with CC genotype was only 0.524 times likely than
those with CT/TT genotype to suffer from NDS. CONCLUSION: PPARgamma gene
rs2921190 polymorphism was correlated with the susceptibility to NDS.
PMID- 29960293
TI - Effect of Icariin on apoptosis and expression of Fas, Fas ligand, B cell
lymphoma, and Bcl-2-associated X protein in CD4+ T lymphocytesfrom patients with
ankylosing spondylitis.
AB - OBJECTIVE: To investigate the effects of icariin on apoptosis and the expression
of Fas, Fas ligand(FasL), B cell lymphoma (Bcl-2), and Bcl-2-associated X protein
(Bax) in CD4+ T lymphocytes from patientswith ankylosing spondylitis. METHODS:
Primary cultures of peripheral blood CD4+ T lymphocytes were established and
treatedwith icariin at high, medium, and low doses (0.5, 0.25, and 0.125 mg/mL).
Sulfasalazine treated andhelthy cells were used as controls. Apoptosis of treated
cells was determined by flow cytometry. Reversetranscription polymerase chain
reaction and enzyme-linked immunosorbent assays were usedto determine the effects
of icariin on the expression of Fas, FasL, Bcl-2, and Bax. The activity of
caspase8 and caspase 3 was determined by a colorimetric assay. RESULTS: The mRNA
and protein expression of Fas, and activity of caspase 8 and caspase 3 in CD4+
Tlymphocytes were increased by icariin (P < 0.05). Conversely, the mRNA and
protein expression ofBcl-2 was decreased (P < 0.05). The expression of FasL and
Bax were not significantly different betweengroups. The proapoptotic effects of
icariin were dose-dependent. CONCLUSION: Icariin induces the apoptosis of CD4 + T
cells from patients with AS comparing tonormal control. Therefore, the induction
of apoptosis may be the likely mechanism of action of icariin'santirheumatics
activities.
PMID- 29960294
TI - Effects of feet reflexology versus segmental massage in reducing pain and its
intensity, frequency and duration of the attacks in femaleswith migraine: a pilot
study.
AB - OBJECTIVE: To evaluate the effects of feet reflexology versus segmental massage
in reducing painand its intensity, frequency and duration of the attacks in
females suffering from migraine. METHODS: Forty eight females aged 33-58,
suffering from migraine for 2 to 10 years were includedin this study from
November 2013 to November 2015. The study protocol was carried out in
Departmentof Chronic Diseases at the Regional Hospital in Zywiec. In the
reflexology group (RG) the patientsreceived a series of 10 treatments 2 times per
week; in the segmental massage group (SMG) thepatients received a series of 15
treatments 3 times per week. Pain during migraine attacks was assessedusing the
visual analog scale (VAS), and headache features such as intensity (IA),
frequency(FA) and duration (DA) of attacks were assessed before the treatment,
just after the treatment, 3months after the treatment. RESULTS: All variables
(VAS, IA, FA and DA) decreasedwithin RG and SMG 3 months after thetreatment in
compare with the baseline values, andthe differences were statistically
significant. The differencesbetween groups were also statistically significant.
CONCLUSION: Feet reflexology and segmental massage provide a safe alternative for
the pharmacologicaltreatment of migraine. The patients with migraine obtain
significant health benefits withfeet reflexology.
PMID- 29960295
TI - Comparative study on skin temperature response to menstruation at acupuncture
points in healthy volunteers and primary dysmenorrheapatients.
AB - OBJECTIVE: To assess skin temperature response to menstruation at acupuncture
points in primarydysmenorrhea (PD) patients and healthy volunteers so as to
explore acupuncture point specificityin reflecting diseases in the light of skin
temperature. METHODS: Fifty-two PD patients and 49 healthy volunteers were
recruited. Skin temperature measurementswere performed with a skin temperature
assessment device at 10 points. Absolute differencebetween skin temperature of
the same point on the left and right side is used as main outcome measure.
RESULTS: On the first day of menstruation, when menstrual pain attacking in PD
patients, a significantincrease in skin temperature difference was detected at
Taixi (KI 3) compared with the healthygroup (P < 0.01). A significant reduction
in skin temperature difference was detected at Taixi (KI 3) inthe first day of
menstruation compared with those values in the third day after menstruation (P <
0.01)in the healthy group. On the third day after menstruation, a significant
reduction in skin temperaturedifference was found at Zhongdu (LR 6) in PD group
compared with the healthy group (P < 0.05).No significant differences of skin
temperature were detected at other points (P > 0.05). CONCLUSION: The skin
temperature difference at menstruation-relevant points in PD patients didnot all
change significantly more than those in women without PD. Significant difference
was only found in Taixi (KI 3), the Yuan-source point of Kidney meridian.
PMID- 29960296
TI - Baicalin extracted from Huangqin (Radix Scutellariae Baicalensis) induces
apoptosis in gastric cancer cells by regulating B cell lymphoma(Bcl-2)/Bcl-2
associated X protein and activating caspase-3 and caspase-9.
AB - OBJECTIVE: To evaluate the effects of baicalin in human gastric cancer cells,
including apoptosis-inducingeffects, and to investigate its underlying mechanisms
of action. METHODS: Cell proliferation and apoptosis assays were performed to
investigate the anti-proliferation effects of baicalin in human gastric cancer
BGC-823 and MGC-803 cells. Real time-quantitativepolymerase chain reaction and
Western blotting analysis were performed to elucidate the molecularmechanisms
underlying the anti-tumor properties of baicalin. RESULTS: In BGC-823 and MGC-803
gastric cancer cells treated with 80, 120, and 160 MUmol/L baicalinfor 48 h, a 3
(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay showed
thatbaicalin significantly inhibited cell proliferation in a dose-dependent
manner, while flow cytometricanalysis demonstrated that baicalin could induce
apoptosis, also in a dose-dependent manner.Moreover, baicalin up-regulated the
expression of caspase-3, caspase-9, and B cell lymphoma(Bcl-2)-associated X
protein and down-regulated the expression of Bcl-2 at both the mRNA andprotein
level. CONCLUSION: Baicalin has potential as a therapeuticagent for gastric
cancer by inducing apoptosis in cancer cells.
PMID- 29960298
TI - A reactive, scalable, and transferable model for molecular energies from a neural
network approach based on local information.
AB - Despite the ever-increasing computer power, accurate ab initio calculations for
large systems (thousands to millions of atoms) remain infeasible. Instead,
approximate empirical energy functions are used. Most current approaches are
either transferable between different chemical systems, but not particularly
accurate, or they are fine-tuned to a specific application. In this work, a data
driven method to construct a potential energy surface based on neural networks is
presented. Since the total energy is decomposed into local atomic contributions,
the evaluation is easily parallelizable and scales linearly with system size.
With prediction errors below 0.5 kcal mol-1 for both unknown molecules and
configurations, the method is accurate across chemical and configurational space,
which is demonstrated by applying it to datasets from nonreactive and reactive
molecular dynamics simulations and a diverse database of equilibrium structures.
The possibility to use small molecules as reference data to predict larger
structures is also explored. Since the descriptor only uses local information,
high-level ab initio methods, which are computationally too expensive for large
molecules, become feasible for generating the necessary reference data used to
train the neural network.
PMID- 29960297
TI - External use of Ruyanneixiao cream efficiently blocks precancerous mammary
lesions by interfering with glycolysis induced by inhibitionof hypoxia inducible
factor-1alpha, hexokinase 2, phosphofructokinase, and pyruvate kinase M2
expression.
PMID- 29960299
TI - Vibronic exciton theory of singlet fission. III. How vibronic coupling and
thermodynamics promote rapid triplet generation in pentacene crystals.
AB - We extend the vibronic exciton theory introduced in our previous work to study
singlet fission dynamics, in particular addressing recent indications of the
importance of vibronic coupling in this process. A microscopic and non
perturbative treatment of electronic and selected vibrational degrees of freedom
in combination with Redfield theory allows us to dynamically consider clusters of
molecules under conditions close to those in molecular crystals that exhibit
fission. Using bulk pentacene as a concrete example, our results identify a
number of factors that render fission rapid and effective. Strong coupling to
high-frequency Holstein modes generates resonances between the photo-prepared
singlet and product triplet states. We furthermore find the large number of
triplet combinations associated with bulk periodic systems to be critical to the
fission process under such vibronically resonant conditions. In addition, we
present results including, in an approximate manner, the effects of Peierls
coupling, indicating that this factor can both enhance and suppress fission
depending on its interplay with vibronic resonance and thermodynamics.
PMID- 29960300
TI - Benchmarking acid and base dopants with respect to enabling the ice V to XIII and
ice VI to XV hydrogen-ordering phase transitions.
AB - Doping the hydrogen-disordered phases of ice V, VI, and XII with hydrochloric
acid (HCl) has led to the discovery of their hydrogen-ordered counterpart ices
XIII, XV, and XIV. Yet, the mechanistic details of the hydrogen-ordering phase
transitions are still not fully understood. This includes, in particular, the
role of the acid dopant and the defect dynamics that it creates within the ices.
Here we investigate the effects of a wide range of acid and base dopants on the
hydrogen ordering of ices V and VI with calorimetry and X-ray diffraction.
Surprisingly, lithium-hydroxide doping achieves a performance comparable to
hydrofluoric-acid doping in ice V, but it is ineffective in the case of ice VI.
Ice V is therefore the first phase of ice that can be hydrogen-ordered with both
acid and base doping. Hydrobromic-acid doping facilitates hydrogen ordering of
ice VI, but it is ineffective in the case of ice V. HCl is reaffirmed to be the
most effective for both phases which is attributed to a favorable combination of
high solubility and strong acid properties. Sodium-hydroxide, potassium-hydroxide
(as previously shown), and perchloric-acid doping are ineffective for both
phases. These findings highlight the need for future computational studies but
also raise the question why lithium hydroxide is the best-performing alkali
hydroxide for hydrogen-ordering ice V whereas potassium-hydroxide doping is most
effective for the "ordinary" ice Ih.
PMID- 29960301
TI - Decoding entangled transitions: Polyamorphism and stressed rigidity.
AB - There is much to learn from simulation studies of polyamorphism achieved for
systems with different bonding environments. Chalcogenide glasses such as Ge-Se
glasses undergo an elastic phase transition involving important changes in
network connectivity. Stimulated by recent developments of topological constraint
theory, we show that the concept of rigidity can be extended to a broader range
of thermodynamic conditions including densified glasses. After having validated
our structural first principles molecular dynamics models with experimental data
over a broad pressure range for GeSe4, we show that the onset of polyamorphism is
strongly related to the constraint density measuring the degree of rigidity of
the network backbone, while voids and cavities in the structure collapse at very
small pressures. This leads to the identification that the progressive onset of
higher coordinated species typical of high pressure phases is responsible for the
onset of stressed rigidity, although the constraint analysis also indicates
progressive stiffening of bonding angles. Results are compared to stoichiometric
and stressed rigid GeSe2 and to isostatic As2Se3 and then generalized to other
compositions in the Ge-Se binary under pressure.
PMID- 29960302
TI - Communication: Is directed percolation in colloid-polymer mixtures linked to
dynamic arrest?
AB - Using computer simulations, we study the dynamic arrest in a schematic model of
colloid-polymer mixtures combining short-ranged attractions with long-ranged
repulsions. The arrested gel is a dilute rigid network of colloidal particles
bonded due to the strong attractions. Without repulsions, the gel forms at the
spinodal through arrested phase separation. In the ergodic suspension at
sufficiently high densities, colloidal clusters form temporary networks that
percolate space. Recently [M. Kohl et al., Nat. Commun. 7, 11817 (2016)], it has
been proposed that the transition of these networks to directed percolation (DP)
coincides with the onset of the dynamic arrest, thus linking structure to
dynamics. Here, we evaluate for various screening lengths the underlying gas
liquid binodal and the percolation transitions. We find that DP shifts the
continuous percolation line to larger densities, but even beyond this line the
suspension remains ergodic. Only when approaching the spinodal does dynamic
arrest occur. Competing repulsions thus do not modify the qualitative scenario
for non-equilibrium gelation, although the structure of the emerging percolating
network shows some differences.
PMID- 29960303
TI - Genarris: Random generation of molecular crystal structures and fast screening
with a Harris approximation.
AB - We present Genarris, a Python package that performs configuration space screening
for molecular crystals of rigid molecules by random sampling with physical
constraints. For fast energy evaluations, Genarris employs a Harris
approximation, whereby the total density of a molecular crystal is constructed
via superposition of single molecule densities. Dispersion-inclusive density
functional theory is then used for the Harris density without performing a self
consistency cycle. Genarris uses machine learning for clustering, based on a
relative coordinate descriptor developed specifically for molecular crystals,
which is shown to be robust in identifying packing motif similarity. In addition
to random structure generation, Genarris offers three workflows based on
different sequences of successive clustering and selection steps: the "Rigorous"
workflow is an exhaustive exploration of the potential energy landscape, the
"Energy" workflow produces a set of low energy structures, and the "Diverse"
workflow produces a maximally diverse set of structures. The latter is
recommended for generating initial populations for genetic algorithms. Here, the
implementation of Genarris is reported and its application is demonstrated for
three test cases.
PMID- 29960304
TI - High-dimensional fitting of sparse datasets of CCSD(T) electronic energies and
MP2 dipole moments, illustrated for the formic acid dimer and its complex IR
spectrum.
AB - We present high-level, coupled-mode calculations of the infrared spectrum of the
cyclic formic acid dimer. The calculations make use of full-dimensional, ab
initio potential energy and dipole moment surfaces. The potential is a linear
least-squares fit to 13 475 CCSD(T)-F12a/haTZ (haTZ means aug-cc-pVTZ basis set
for O and C, and cc-pVTZ for H) energies, and the dipole moment surface is a fit
to the dipole components, calculated at the MP2/haTZ level of theory. The
variables of both fits are all (45) internuclear distances (actually Morse
variables). The potential, which is fully permutationally invariant, is the one
published recently and the dipole moment surface is newly reported here. Details
of the fits, especially the dipole moment, and the database of configurations are
given. The infrared spectrum of the dimer is calculated by solving the nuclear
Schrodinger equation using a vibrational self-consistent field and virtual-state
configuration interaction method, with subsets of the 24 normal modes, up to 15
modes. The calculations indicate strong mode-coupling in the C-H and O-H
stretching region of the spectrum. Comparisons are made with experiments and the
complexity of the experimental spectrum in the C-H and O-H stretching region is
successfully reproduced.
PMID- 29960305
TI - Refining Markov state models for conformational dynamics using ensemble-averaged
data and time-series trajectories.
AB - A data-driven modeling scheme is proposed for conformational dynamics of
biomolecules based on molecular dynamics (MD) simulations and experimental
measurements. In this scheme, an initial Markov State Model (MSM) is constructed
from MD simulation trajectories, and then, the MSM parameters are refined using
experimental measurements through machine learning techniques. The second step
can reduce the bias of MD simulation results due to inaccurate force-field
parameters. Either time-series trajectories or ensemble-averaged data are
available as a training data set in the scheme. Using a coarse-grained model of a
dye-labeled polyproline-20, we compare the performance of machine learning
estimations from the two types of training data sets. Machine learning from time
series data could provide the equilibrium populations of conformational states as
well as their transition probabilities. It estimates hidden conformational states
in more robust ways compared to that from ensemble-averaged data although there
are limitations in estimating the transition probabilities between minor states.
We discuss how to use the machine learning scheme for various experimental
measurements including single-molecule time-series trajectories.
PMID- 29960306
TI - Exponential propagators for the Schrodinger equation with a time-dependent
potential.
AB - We consider the numerical integration of the Schrodinger equation with a time
dependent Hamiltonian given as the sum of the kinetic energy and a time-dependent
potential. Commutator-free (CF) propagators are exponential propagators that have
shown to be highly efficient for general time-dependent Hamiltonians. We propose
new CF propagators that are tailored for Hamiltonians of the said structure,
showing a considerably improved performance. We obtain new fourth- and sixth
order CF propagators as well as a novel sixth-order propagator that incorporates
a double commutator that only depends on coordinates, so this term can be
considered as cost-free. The algorithms require the computation of the action of
exponentials on a vector similar to the well-known exponential midpoint
propagator, and this is carried out using the Lanczos method. We illustrate the
performance of the new methods on several numerical examples.
PMID- 29960307
TI - Sparse learning of stochastic dynamical equations.
AB - With the rapid increase of available data for complex systems, there is great
interest in the extraction of physically relevant information from massive
datasets. Recently, a framework called Sparse Identification of Nonlinear
Dynamics (SINDy) has been introduced to identify the governing equations of
dynamical systems from simulation data. In this study, we extend SINDy to
stochastic dynamical systems which are frequently used to model biophysical
processes. We prove the asymptotic correctness of stochastic SINDy in the
infinite data limit, both in the original and projected variables. We discuss
algorithms to solve the sparse regression problem arising from the practical
implementation of SINDy and show that cross validation is an essential tool to
determine the right level of sparsity. We demonstrate the proposed methodology on
two test systems, namely, the diffusion in a one-dimensional potential and the
projected dynamics of a two-dimensional diffusion process.
PMID- 29960308
TI - Langevin dynamics simulation of crystallization of ring polymers.
AB - We have studied the crystallization of ring polymers using Langevin dynamics
simulations with a coarse-grained united atom model. We show that there are
marked differences in the crystallization of single ring polymers in comparison
to single linear polymers. Contrary to expectations from equilibrium
thermodynamics, ring polymers melt at lower temperatures than linear polymers. An
analysis of the early stage crystallization mechanism shows that ring and linear
polymers crystallize through the birth of baby nuclei with their coarsening
depending uniquely on their topology. The single ring polymers nucleate faster
than the single linear analogs and into several metastable lamellar thicknesses,
although the motion of the monomers in both cases is comparable. Additionally,
using multiple polymer molecules, we find that the secondary nucleation of ring
polymers proceeds with free energy barriers, as opposed to linear polymers where
no barriers are found. Our results are in qualitative agreement with some
experiments, while in disagreement with some other experiments, indicating
additional roles by chemistries of ring and linear polymers. Our simulations are
designed to explore only the topological effects without any consideration of non
universal chemical effects for our particular model.
PMID- 29960309
TI - Note: Diffusion-limited annihilation in cavities.
PMID- 29960310
TI - A description of hydroquinone clathrates using molecular dynamics: Molecular
model and crystalline structures for CH4 and CO2 guests.
AB - The crystalline structure of hydroquinone clathrates has been studied using
molecular dynamics. A flexible non-polarizable all-atom molecular model, based on
the original Optimized Potentials for Liquid Simulations force field with
recalculated point electric charges, has been used to describe the hydroquinone
molecule, and the crystalline solid structure of the alpha native phase has been
analyzed. Then, the beta clathrates have been studied, considering CO2 and CH4 as
guest molecules, and also the empty clathrate structure. In all cases, the
lattice parameters obtained through molecular simulation show excellent agreement
with reported experimental values, showing that the molecular model selected is
able to reproduce both the native crystalline phase and also the clathrate
structures. In addition, the process of clathrate guest molecule release upon
heating has been characterized, and the simulations show a good correspondence
with the very recent experimental trends observed for both guest molecules
analyzed.
PMID- 29960311
TI - Hierarchical modeling of molecular energies using a deep neural network.
AB - We introduce the Hierarchically Interacting Particle Neural Network (HIP-NN) to
model molecular properties from datasets of quantum calculations. Inspired by a
many-body expansion, HIP-NN decomposes properties, such as energy, as a sum over
hierarchical terms. These terms are generated from a neural network-a composition
of many nonlinear transformations-acting on a representation of the molecule. HIP
NN achieves the state-of-the-art performance on a dataset of 131k ground state
organic molecules and predicts energies with 0.26 kcal/mol mean absolute error.
With minimal tuning, our model is also competitive on a dataset of molecular
dynamics trajectories. In addition to enabling accurate energy predictions, the
hierarchical structure of HIP-NN helps to identify regions of model uncertainty.
PMID- 29960312
TI - Guest Editorial: Special Topic on Data-Enabled Theoretical Chemistry.
AB - A survey of the contributions to the Special Topic on Data-enabled Theoretical
Chemistry is given, including a glossary of relevant machine learning terms.
PMID- 29960313
TI - New nickel-based hybrid organic/inorganic metal halide for photovoltaic
applications.
AB - In this work, we have synthesized and fabricated solar cells with the hybrid
metal halide compounds with the general formula ABX3, where the A cation is
methylammonium, the B cation is nickel, and the X anion is chlorine or a mixture
of chlorine and iodine. We obtained experimental evidence that this material is a
semiconductor with an orthorhombic crystalline structure which pertains to the
space group Cmcm. The bandgap can be modulated from 1.4 eV to 1.0 eV by changing
the chlorine anion to iodine. Therefore, we were able to obtain solar cells with
efficiencies up to 0.16% with the CH3NH3NiCl2I composition. We have also studied
by means of first-principles calculations, taking into account van der Waals
dispersive forces, the ground state properties of these materials such as their
crystal structure and formation and decomposition energies. We have found that
these energies are lowered by the lighter mass anion, and the calculated
decomposition energies show that only CH3NH3NiCl3 is stable with respect to the
most probable decomposition pathway. The electronic band structure and band edge
alignments have been calculated using quasiparticle effects through the GW0
approximation; these materials show an indirect bandgap with the valence band
maxima at -6.93 and -5.49 eV with respect to vacuum and the conduction band
minima at -5.62 and -4.60 eV with respect to vacuum for CH3NH3NiCl3 and
CH3NH3NiI3, respectively. This work provides a pathway to explore new hybrid
A+B2+X3--type semiconductor materials.
PMID- 29960314
TI - Criegee intermediate inside fullerene cage: Evidence for size-dependent
reactivity.
AB - In the theoretical calculations reported here, we show that the hydration of the
Criegee intermediate within the sub-nanospace of fullerene cages occurs
differently in different fullerenes, thereby providing evidence for the size
dependent reactivity inside these exotic carbon cages. Upon C70 or C84
encapsulation, the Criegee hydration occurs instantaneously without any
activation barrier, whereas inside the C120 cage, the hydration involves a small
barrier of 4.4 kcal/mol. Our Born-Oppenheimer molecular dynamics simulations
suggest that the Criegee intermediate and the product of its hydration, alpha
hydroxy methyl hydroperoxide, remain dynamically stable over 20 ps time scale at
the 300 K, implying that fullerene cages provide a robust framework for
reactivity.
PMID- 29960315
TI - When Hartree-Fock exchange admixture lowers DFT-predicted barrier heights:
Natural bond orbital analyses and implications for catalysis.
AB - The conventional wisdom in density functional theory (DFT) is that standard
approximations systematically underestimate chemical reaction barrier heights and
that exact (Hartree-Fock-like, HF) exchange admixture improves this. This
conventional wisdom is inconsistent with the good performance of functionals
without HF exchange for many reactions on metal catalyst surfaces. We have
studied several "anomalous" gas-phase reactions where this conventional wisdom is
upended, and a HF exchange admixture decreases or does not affect the predicted
barrier heights [Mahler et al., J. Chem. Phys. 146, 234103 (2017)]. Here we show
how natural bond orbital analyses can help identify and explain some factors that
produce anomalous barriers. Applications to pnictogen inversion, standard
benchmark reaction barrier datasets, and a model Grubbs catalyst illustrate the
utility of this approach. This approach is expected to aid DFT users in choosing
appropriate functionals, and aid DFT developers in devising DFT approximations
generally applicable to catalysis.
PMID- 29960316
TI - Comparison of permutationally invariant polynomials, neural networks, and
Gaussian approximation potentials in representing water interactions through many
body expansions.
AB - The accurate representation of multidimensional potential energy surfaces is a
necessary requirement for realistic computer simulations of molecular systems.
The continued increase in computer power accompanied by advances in correlated
electronic structure methods nowadays enables routine calculations of accurate
interaction energies for small systems, which can then be used as references for
the development of analytical potential energy functions (PEFs) rigorously
derived from many-body (MB) expansions. Building on the accuracy of the MB-pol
many-body PEF, we investigate here the performance of permutationally invariant
polynomials (PIPs), neural networks, and Gaussian approximation potentials (GAPs)
in representing water two-body and three-body interaction energies, denoting the
resulting potentials PIP-MB-pol, Behler-Parrinello neural network-MB-pol, and GAP
MB-pol, respectively. Our analysis shows that all three analytical
representations exhibit similar levels of accuracy in reproducing both two-body
and three-body reference data as well as interaction energies of small water
clusters obtained from calculations carried out at the coupled cluster level of
theory, the current gold standard for chemical accuracy. These results
demonstrate the synergy between interatomic potentials formulated in terms of a
many-body expansion, such as MB-pol, that are physically sound and transferable,
and machine-learning techniques that provide a flexible framework to approximate
the short-range interaction energy terms.
PMID- 29960317
TI - Gaussian process regression to accelerate geometry optimizations relying on
numerical differentiation.
AB - We study how with means of Gaussian Process Regression (GPR) geometry
optimizations, which rely on numerical gradients, can be accelerated. The GPR
interpolates a local potential energy surface on which the structure is
optimized. It is found to be efficient to combine results on a low computational
level (HF or MP2) with the GPR-calculated gradient of the difference between the
low level method and the target method, which is a variant of explicitly
correlated Coupled Cluster Singles and Doubles with perturbative Triples
correction CCSD(F12*)(T) in this study. Overall convergence is achieved if both
the potential and the geometry are converged. Compared to numerical gradient
based algorithms, the number of required single point calculations is reduced.
Although introducing an error due to the interpolation, the optimized structures
are sufficiently close to the minimum of the target level of theory meaning that
the reference and predicted minimum only vary energetically in the MUEh regime.
PMID- 29960318
TI - Investigating photoinduced proton coupled electron transfer reaction using quasi
diabatic dynamics propagation.
AB - We investigate photoinduced proton-coupled electron transfer (PI-PCET) reactions
through a recently developed quasi-diabatic (QD) quantum dynamics propagation
scheme. This scheme enables interfacing accurate diabatic-based quantum dynamics
approaches with adiabatic electronic structure calculations for on-the-fly
simulations. Here, we use the QD scheme to directly propagate PI-PCET quantum
dynamics with the diabatic partial linearized density matrix path-integral
approach with the instantaneous adiabatic electron-proton vibronic states. Our
numerical results demonstrate the importance of treating protons quantum
mechanically in order to obtain accurate PI-PCET dynamics as well as the role of
solvent fluctuation and vibrational relaxation on proton tunneling in various
reaction regimes that exhibit different kinetic isotope effects. This work opens
the possibility to study the challenging PI-PCET reactions through accurate
diabatic quantum dynamics approaches combined with efficient adiabatic electronic
structure calculations.
PMID- 29960319
TI - Scattering of CO with H2O: Statistical and classical alternatives to close
coupling calculations.
AB - Energy transfer in inelastic atom-molecule and molecule-molecule collisions can
be described theoretically using the quantum-mechanical close-coupling method.
Unfortunately, for bimolecular collisions implying heavy colliders and/or for
which the potential energy surface has a deep well, the resulting coupled
equations become numerically intractable and approximate methods have to be
employed. H2O-CO collisions provide an important example for which close-coupling
calculations are not feasible. In this paper, we investigate the accuracy of
three approximate methods (the coupled states method, the quasi-classical
trajectory method, and the statistical adiabatic channel model) to describe
inelastic collisions of H2O with CO. We perform scattering calculations on a
recent 5D potential energy surface, and we compare the results of the three
approximate methods to fully converged close-coupling calculations at energies
below 300 cm-1 and at low values of the total angular momentum. We show that the
statistical method provides an attractive alternative to fully quantum mechanical
close-coupling calculations at low collision energies, while the quasi-classical
method is more advantageous at high energies.
PMID- 29960320
TI - Combining first-principles and data modeling for the accurate prediction of the
refractive index of organic polymers.
AB - Organic materials with a high index of refraction (RI) are attracting
considerable interest due to their potential application in optic and
optoelectronic devices. However, most of these applications require an RI value
of 1.7 or larger, while typical carbon-based polymers only exhibit values in the
range of 1.3-1.5. This paper introduces an efficient computational protocol for
the accurate prediction of RI values in polymers to facilitate in silico studies
that can guide the discovery and design of next-generation high-RI materials. Our
protocol is based on the Lorentz-Lorenz equation and is parametrized by the
polarizability and number density values of a given candidate compound. In the
proposed scheme, we compute the former using first-principles electronic
structure theory and the latter using an approximation based on van der Waals
volumes. The critical parameter in the number density approximation is the
packing fraction of the bulk polymer, for which we have devised a machine
learning model. We demonstrate the performance of the proposed RI protocol by
testing its predictions against the experimentally known RI values of 112 optical
polymers. Our approach to combine first-principles and data modeling emerges as
both a successful and a highly economical path to determining the RI values for a
wide range of organic polymers.
PMID- 29960321
TI - Constructing first-principles phase diagrams of amorphous LixSi using machine
learning-assisted sampling with an evolutionary algorithm.
AB - The atomistic modeling of amorphous materials requires structure sizes and
sampling statistics that are challenging to achieve with first-principles
methods. Here, we propose a methodology to speed up the sampling of amorphous and
disordered materials using a combination of a genetic algorithm and a specialized
machine-learning potential based on artificial neural networks (ANNs). We show
for the example of the amorphous LiSi alloy that around 1000 first-principles
calculations are sufficient for the ANN-potential assisted sampling of low-energy
atomic configurations in the entire amorphous LixSi phase space. The obtained
phase diagram is validated by comparison with the results from an extensive
sampling of LixSi configurations using molecular dynamics simulations and a
general ANN potential trained to ~45 000 first-principles calculations. This
demonstrates the utility of the approach for the first-principles modeling of
amorphous materials.
PMID- 29960322
TI - SchNet - A deep learning architecture for molecules and materials.
AB - Deep learning has led to a paradigm shift in artificial intelligence, including
web, text, and image search, speech recognition, as well as bioinformatics, with
growing impact in chemical physics. Machine learning, in general, and deep
learning, in particular, are ideally suitable for representing quantum-mechanical
interactions, enabling us to model nonlinear potential-energy surfaces or
enhancing the exploration of chemical compound space. Here we present the deep
learning architecture SchNet that is specifically designed to model atomistic
systems by making use of continuous-filter convolutional layers. We demonstrate
the capabilities of SchNet by accurately predicting a range of properties across
chemical space for molecules and materials, where our model learns chemically
plausible embeddings of atom types across the periodic table. Finally, we employ
SchNet to predict potential-energy surfaces and energy-conserving force fields
for molecular dynamics simulations of small molecules and perform an exemplary
study on the quantum-mechanical properties of C20-fullerene that would have been
infeasible with regular ab initio molecular dynamics.
PMID- 29960323
TI - Anion photoelectron spectroscopy and chemical bonding of ThO2- and ThO3.
AB - We conducted a study of electronic structures and chemical bonding of gaseous
ThO2- and ThO3- using velocity-map imaging and ab initio calculations. The
electron affinity of neutral ThO2 molecule is reported for the first time with
the value of 1.21(5) eV. We obtained a vibrationally resolved photoelectron
spectroscopy of ThO2- and observed the symmetric stretching frequency of 824(40)
cm-1 for neutral molecules. One hot band transition is observed in the spectrum
of ThO2-, which allows the measurement of symmetric stretching mode for ThO2-.
The ground state of ThO2- is 2A1 with C2v symmetry: the detachment of an electron
from the singly occupied molecular orbital (SOMO) results in the ground state of
ThO2. Kohn-Sham molecular orbital analyses reveal an sigma and two weak pi bonds
for Th-O multiple bonds in ThO2. Global minimum search methodology combined with
quantum chemical calculations are used to find the minima of ThO3 and ThO3-, and
the adiabatic detachment energy of ThO3- is calculated to be 3.26 eV at the
coupled cluster with singles and doubles plus perturbative triples level. Our
theoretical calculations suggest that the ground state of ThO3 is 1A' with a
symmetry of Cs, while the most stable ThO3- is 2A1 with C2v symmetry; thus, the
transition from ThO3- to ThO3 undergoes a significant geometry reorganization.
Molecular orbital analyses suggest that the SOMO of ThO3- is mainly participated
by O 2p and O to Th back donation was found in HOMO-2 molecular orbital. This
investigation will shed some light on the understanding of covalent bonding in Th
contained molecules.
PMID- 29960324
TI - Neural-network Kohn-Sham exchange-correlation potential and its out-of-training
transferability.
AB - We incorporate in the Kohn-Sham self-consistent equation a trained neural-network
projection from the charge density distribution to the Hartree-exchange
correlation potential n -> VHxc for a possible numerical approach to the exact
Kohn-Sham scheme. The potential trained through a newly developed scheme enables
us to evaluate the total energy without explicitly treating the formula of the
exchange-correlation energy. With a case study of a simple model, we show that
the well-trained neural-network VHxc achieves accuracy for the charge density and
total energy out of the model parameter range used for the training, indicating
that the property of the elusive ideal functional form of VHxc can approximately
be encapsulated by the machine-learning construction. We also exemplify a factor
that crucially limits the transferability-the boundary in the model parameter
space where the number of the one-particle bound states changes-and see that this
is cured by setting the training parameter range across that boundary. The
training scheme and insights from the model study apply to more general systems,
opening a novel path to numerically efficient Kohn-Sham potential.
PMID- 29960325
TI - A near-linear scaling equation of motion coupled cluster method for ionized
states.
AB - In this work, a domain-based local pair natural orbital (DLPNO) version of the
equation of motion coupled cluster theory with single and double excitations for
ionization potentials (IP-EOM-CCSD) equations has been formulated and
implemented. The method uses ground state localized occupied and pair natural
virtual orbitals and applies the DLPNO machinery to arrive at a linear scaling
implementation of the IP-EOM-CCSD method. The accuracy of the method is
controllable using ground state truncation parameters. Using default thresholds,
the method predicts ionization potential (IP) values with good accuracy (mean
absolute error of 0.08 eV). We demonstrate that our code can be used to compute
IP values for systems with more than 1000 atoms and 10 000 basis functions.
PMID- 29960326
TI - Rheology of the lambda transition in liquid sulfur: Insights from arsenic sulfide
liquids.
AB - The frequency dependence of the storage and loss shear moduli and viscosity of
AsxS100-x glass-forming liquids (x = 5, 10, 15, 40) are obtained over a frequency
range covering nearly 15 orders of magnitude using parallel plate rheometry. The
S-rich (x <= 15) liquids are characterized by a ring-to-chain structural
transition near Tlambda ~ 120 degrees C, and their rheological behavior below
Tlambda strongly resembles that of long-chain and entangled polymers as well as
that recently speculated for liquid sulfur above its lambda transition. These
AsxS100-x liquids are characterized by the coexistence of a slow and a fast
relaxation process with similar activation energy. Both processes are coupled to
viscosity, but differ in time scale by several orders in magnitude and are
assigned, respectively, to the reptation and the Rouse dynamics of the Sn chains
in these liquids. Such complex polymer-like rheological behavior disappears in
the As40S60 liquid, characterized by corner-shared AsS3/2 pyramids, where a
single average shear relaxation time typical of simple liquids instead emerges.
PMID- 29960327
TI - Probabilistic performance estimators for computational chemistry methods: The
empirical cumulative distribution function of absolute errors.
AB - Benchmarking studies in computational chemistry use reference datasets to assess
the accuracy of a method through error statistics. The commonly used error
statistics, such as the mean signed and mean unsigned errors, do not inform end
users on the expected amplitude of prediction errors attached to these methods.
We show that, the distributions of model errors being neither normal nor zero
centered, these error statistics cannot be used to infer prediction error
probabilities. To overcome this limitation, we advocate for the use of more
informative statistics, based on the empirical cumulative distribution function
of unsigned errors, namely, (1) the probability for a new calculation to have an
absolute error below a chosen threshold and (2) the maximal amplitude of errors
one can expect with a chosen high confidence level. Those statistics are also
shown to be well suited for benchmarking and ranking studies. Moreover, the
standard error on all benchmarking statistics depends on the size of the
reference dataset. Systematic publication of these standard errors would be very
helpful to assess the statistical reliability of benchmarking conclusions.
PMID- 29960328
TI - Accelerating molecular discovery through data and physical sciences: Applications
to peptide-membrane interactions.
AB - Simulation and data analysis have evolved into powerful methods for discovering
and understanding molecular modes of action and designing new compounds to
exploit these modes. The combination provides a strong impetus to create and
exploit new tools and techniques at the interfaces between physics, biology, and
data science as a pathway to new scientific insight and accelerated discovery. In
this context, we explore the rational design of novel antimicrobial peptides
(short protein sequences exhibiting broad activity against multiple species of
bacteria). We show how datasets can be harvested to reveal features which inform
new design concepts. We introduce new analysis and visualization tools: a
graphical representation of the k-mer spectrum as a fundamental property encoded
in antimicrobial peptide databases and a data-driven representation to illustrate
membrane binding and permeation of helical peptides.
PMID- 29960329
TI - Rotational-mode specific effects on the stereo-requirement in the reaction of
prealigned-CHD3(v1 = 1; |JK = |10 or |1 +/- 1) with the chlorine atom.
AB - Several aspects of the stereo-specific requirement in the title reaction are
systematically investigated in a crossed-beam experiment using a time-sliced,
velocity-mapped imaging technique. Specifically, we explored (1) the differential
steric effect from pre-aligning two different reagent rotational states and (2)
the effect from probing different product rotational states. In the reaction with
an aligned JK=10 reagent at Ec = 3.2 kcal mol-1, the head-on geometry yields a
predominantly backward-scattered CD3(00) + HCl(v = 0) product pair, whereas the
side-on approach results in a pronounced sideway-scattered distribution. The
alternative CD3(00) + HCl(v = 1) channel exhibits a sharply forward-scattering
feature for both the collisional geometries. The branching of the two product
channels shows sensitive dependency on the collisional geometries. Probing
different rotational states of CD3(00) reveals little variation in pair
correlated angular distributions, yet yields notable effect on the correlated
vibrational branching of the HCl(v = 0, 1) coproducts. Similar steric
propensities hold at lower collisional energy of 1.3 kcal mol-1. In stark
contrast, diminishing steric effects were observed in the reaction with an
aligned 1+/-1 reagent. Such huge differential, K-dependent stereo-requirements
are largely attributed to the distinct "shapes" of the two rotational states of
the aligned CHD3(v1 = 1) reagents.
PMID- 29960330
TI - Non-covalent interactions across organic and biological subsets of chemical
space: Physics-based potentials parametrized from machine learning.
AB - Classical intermolecular potentials typically require an extensive
parametrization procedure for any new compound considered. To do away with prior
parametrization, we propose a combination of physics-based potentials with
machine learning (ML), coined IPML, which is transferable across small neutral
organic and biologically relevant molecules. ML models provide on-the-fly
predictions for environment-dependent local atomic properties: electrostatic
multipole coefficients (significant error reduction compared to previously
reported), the population and decay rate of valence atomic densities, and
polarizabilities across conformations and chemical compositions of H, C, N, and O
atoms. These parameters enable accurate calculations of intermolecular
contributions-electrostatics, charge penetration, repulsion,
induction/polarization, and many-body dispersion. Unlike other potentials, this
model is transferable in its ability to handle new molecules and conformations
without explicit prior parametrization: All local atomic properties are predicted
from ML, leaving only eight global parameters-optimized once and for all across
compounds. We validate IPML on various gas-phase dimers at and away from
equilibrium separation, where we obtain mean absolute errors between 0.4 and 0.7
kcal/mol for several chemically and conformationally diverse datasets
representative of non-covalent interactions in biologically relevant molecules.
We further focus on hydrogen-bonded complexes-essential but challenging due to
their directional nature-where datasets of DNA base pairs and amino acids yield
an extremely encouraging 1.4 kcal/mol error. Finally, and as a first look, we
consider IPML for denser systems: water clusters, supramolecular host-guest
complexes, and the benzene crystal.
PMID- 29960331
TI - Extending the accuracy of the SNAP interatomic potential form.
AB - The Spectral Neighbor Analysis Potential (SNAP) is a classical interatomic
potential that expresses the energy of each atom as a linear function of selected
bispectrum components of the neighbor atoms. An extension of the SNAP form is
proposed that includes quadratic terms in the bispectrum components. The
extension is shown to provide a large increase in accuracy relative to the linear
form, while incurring only a modest increase in computational cost. The
mathematical structure of the quadratic SNAP form is similar to the embedded atom
method (EAM), with the SNAP bispectrum components serving as counterparts to the
two-body density functions in EAM. The effectiveness of the new form is
demonstrated using an extensive set of training data for tantalum structures.
Similar to artificial neural network potentials, the quadratic SNAP form requires
substantially more training data in order to prevent overfitting. The quality of
this new potential form is measured through a robust cross-validation analysis.
PMID- 29960333
TI - Structure prediction of boron-doped graphene by machine learning.
AB - Heteroatom doping has endowed graphene with manifold aspects of material
properties and boosted its applications. The atomic structure determination of
doped graphene is vital to understand its material properties. Motivated by the
recently synthesized boron-doped graphene with relatively high concentration,
here we employ machine learning methods to search the most stable structures of
doped boron atoms in graphene, in conjunction with the atomistic simulations.
From the determined stable structures, we find that in the free-standing pristine
graphene, the doped boron atoms energetically prefer to substitute for the carbon
atoms at different sublattice sites and that the para configuration of boron
boron pair is dominant in the cases of high boron concentrations. The boron
doping can increase the work function of graphene by 0.7 eV for a boron content
higher than 3.1%.
PMID- 29960332
TI - Survival of the most transferable at the top of Jacob's ladder: Defining and
testing the omegaB97M(2) double hybrid density functional.
AB - A meta-generalized gradient approximation, range-separated double hybrid (DH)
density functional with VV10 non-local correlation is presented. The final 14
parameter functional form is determined by screening trillions of candidate fits
through a combination of best subset selection, forward stepwise selection, and
random sample consensus (RANSAC) outlier detection. The MGCDB84 database of 4986
data points is employed in this work, containing a training set of 870 data
points, a validation set of 2964 data points, and a test set of 1152 data points.
Following an xDH approach, orbitals from the omegaB97M-V density functional are
used to compute the second-order perturbation theory correction. The resulting
functional, omegaB97M(2), is benchmarked against a variety of leading double
hybrid density functionals, including B2PLYP-D3(BJ), B2GPPLYP-D3(BJ), omegaB97X
2(TQZ), XYG3, PTPSS-D3(0), XYGJ-OS, DSD-PBEP86-D3(BJ), and DSD-PBEPBE-D3(BJ).
Encouragingly, the overall performance of omegaB97M(2) on nearly 5000 data points
clearly surpasses that of all of the tested density functionals. As a Rung 5
density functional, omegaB97M(2) completes our family of combinatorially
optimized functionals, complementing B97M-V on Rung 3, and omegaB97X-V and
omegaB97M-V on Rung 4. The results suggest that omegaB97M(2) has the potential to
serve as a powerful predictive tool for accurate and efficient electronic
structure calculations of main-group chemistry.
PMID- 29960334
TI - Physics-informed machine learning for inorganic scintillator discovery.
AB - Applications of inorganic scintillators-activated with lanthanide dopants, such
as Ce and Eu-are found in diverse fields. As a strict requirement to exhibit
scintillation, the 4f ground state (with the electronic configuration of [Xe]4fn
5d0) and 5d1 lowest excited state (with the electronic configuration of [Xe]4fn-1
5d1) levels induced by the activator must lie within the host bandgap. Here we
introduce a new machine learning (ML) based search strategy for high-throughput
chemical space explorations to discover and design novel inorganic scintillators.
Building upon well-known physics-based chemical trends for the host dependent
electron binding energies within the 4f and 5d1 energy levels of lanthanide ions
and available experimental data, the developed ML model-coupled with knowledge of
the vacuum referred valence and conduction band edges computed from first
principles-can rapidly and reliably estimate the relative positions of the
activator's energy levels relative to the valence and conduction band edges of
any given host chemistry. Using perovskite oxides and elpasolite halides as
examples, the presented approach has been demonstrated to be able to (i) capture
systematic chemical trends across host chemistries and (ii) effectively screen
promising compounds in a high-throughput manner. While a number of other
application-specific performance requirements need to be considered for a viable
scintillator, the scheme developed here can be a practically useful tool to
systematically down-select the most promising candidate materials in a first line
of screening for a subsequent in-depth investigation.
PMID- 29960335
TI - How do hydrogen bonds break in supercooled water?: Detecting pathways not going
through saddle point of two-dimensional potential of mean force.
AB - Supercooled water exhibits remarkably slow dynamics similar to the behavior
observed for various glass-forming liquids. The local order of tetrahedral
structures due to hydrogen-bonds (H-bonds) increases with decreasing temperature.
Thus, it is important to clarify the temperature dependence of the H-bond
breakage process. This was investigated here using molecular dynamics simulations
of TIP4P supercooled water. The two-dimensional (2D) potential of mean force
(PMF) is presented using combinations of intermolecular distance and angle
between two water molecules. The saddle point of the 2D PMF suggests the presence
of the transition state that distinguishes between H-bond and non H-bond states.
However, we observed pathways not going through this saddle point particularly at
supercooled states, which are due to translational rather than rotational motions
of the molecules. We quantified the characteristic time scales of rotational and
translational H-bond breakages. The time scale of the translational H-bond
breakage shows a non-Arrhenius temperature dependence comparable to that of the H
bond lifetime. This time scale is relevant for the temperature dependence of the
transmission coefficient based on the transition state theory. The translational
H-bond breakage is also related to cage-jumps observed in glass-forming liquids,
which mostly involve spatially correlated molecules. Our findings warrant further
exploration of an appropriate free-energy surface or reaction coordinates beyond
the geometrical variables of the water dimer to describe a possible saddle point
related to collective jump motions.
PMID- 29960337
TI - Machine learning approaches to evaluate correlation patterns in allosteric
signaling: A case study of the PDZ2 domain.
AB - Many proteins are regulated by dynamic allostery wherein regulator-induced
changes in structure are comparable with thermal fluctuations. Consequently,
understanding their mechanisms requires assessment of relationships between and
within conformational ensembles of different states. Here we show how machine
learning based approaches can be used to simplify this high-dimensional data
mining task and also obtain mechanistic insight. In particular, we use these
approaches to investigate two fundamental questions in dynamic allostery. First,
how do regulators modify inter-site correlations in conformational fluctuations
(Cij)? Second, how are regulator-induced shifts in conformational ensembles at
two different sites in a protein related to each other? We address these
questions in the context of the human protein tyrosine phosphatase 1E's PDZ2
domain, which is a model protein for studying dynamic allostery. We use molecular
dynamics to generate conformational ensembles of the PDZ2 domain in both the
regulator-bound and regulator-free states. The employed protocol reproduces
methyl deuterium order parameters from NMR. Results from unsupervised clustering
of Cij combined with flow analyses of weighted graphs of Cij show that regulator
binding significantly alters the global signaling network in the protein;
however, not by altering the spatial arrangement of strongly interacting amino
acid clusters but by modifying the connectivity between clusters. Additionally,
we find that regulator-induced shifts in conformational ensembles, which we
evaluate by repartitioning ensembles using supervised learning, are, in fact,
correlated. This correlation Deltaij is less extensive compared to Cij, but in
contrast to Cij, Deltaij depends inversely on the distance from the regulator
binding site. Assuming that Deltaij is an indicator of the transduction of the
regulatory signal leads to the conclusion that the regulatory signal weakens with
distance from the regulatory site. Overall, this work provides new approaches to
analyze high-dimensional molecular simulation data and also presents applications
that yield new insight into dynamic allostery.
PMID- 29960336
TI - Can exact conditions improve machine-learned density functionals?
AB - Historical methods of functional development in density functional theory have
often been guided by analytic conditions that constrain the exact functional one
is trying to approximate. Recently, machine-learned functionals have been created
by interpolating the results from a small number of exactly solved systems to
unsolved systems that are similar in nature. For a simple one-dimensional system,
using an exact condition, we find improvements in the learning curves of a
machine learning approximation to the non-interacting kinetic energy functional.
We also find that the significance of the improvement depends on the nature of
the interpolation manifold of the machine-learned functional.
PMID- 29960338
TI - Mixed quantum/classical theory for rotationally and vibrationally inelastic
scattering of open-shell molecules and its application to the NH(X3Sigma-) + He
collisional system.
AB - We developed the mixed quantum/classical theory (MQCT) for rotationally and
vibrationally inelastic scattering of a diatomic molecule in a 2S+1Sigma
electronic state with a closed-shell atom. In this approach, the rotational (and
vibrational) fine-structure states of the molecule are treated quantum
mechanically, whereas the relative motion of collisional partners is treated
classically. This theory is benchmarked against full quantum (close-coupling)
calculations for the NH(X3Sigma-) + He system. Good agreement is found in all
cases, and MQCT reproduces all main features of energy dependence of the cross
section, except narrow scattering resonances at very low energies. Our method
recovers propensity rules that govern values of close-coupling cross sections.
Particularly, MQCT correctly predicts that the magnitudes of F-conserving
transitions are significantly larger than those of F-changing ones. This new
development makes MQCT a viable candidate for obtaining fine-structure resolved
rotational rate coefficients at higher temperatures and for complex polyatomic
systems where the standard full quantum treatment is computationally infeasible.
PMID- 29960339
TI - Searching the stable segregation configuration at the grain boundary by a Monte
Carlo tree search.
AB - Non-stoichiometric structure localized at the grain boundary, namely,
segregations of impurities, dopants, and vacancies, has an important effect on a
broad variety of material properties. An understanding of this behavior is
therefore indispensable for further material development. Although molecular
dynamics simulation and a simulation combined with randomly swapping atoms and
vacancies have usually been used to investigate the segregation structures, they
require more than ten thousand structures and energy calculations to reach the
stable configuration. Although several mathematical or informatics approaches,
for example, genetic algorithm and Bayesian optimization, have been proposed to
solve such combination optimization problems, they required some hyper parameters
which crucially affect efficiency and huge computations to tune these parameters.
Furthermore, a parallelization of the computation task is often impossible in
molecular dynamics simulation and Bayesian optimization because their structures
are related to each other before and after the time or simulation steps. Here, we
develop a Monte Carlo tree search algorithm for grain boundary segregation and
apply it to determine the stable segregation configuration of copper
Sigma5[001]/(210) and Sigma37[001]/(750) with silver impurities. We achieved a
determination of the stable configuration by searching only 1% of all possible
configurations. Furthermore, we found that the search path and the number of
playouts at the branch provide important insight to comprehend the background of
the search. In the present case, the search path was identical to the sites with
the spatially larger sites.
PMID- 29960340
TI - Maximally resolved anharmonic OH vibrational spectrum of the water/ZnO(101-0)
interface from a high-dimensional neural network potential.
AB - Unraveling the atomistic details of solid/liquid interfaces, e.g., by means of
vibrational spectroscopy, is of vital importance in numerous applications, from
electrochemistry to heterogeneous catalysis. Water-oxide interfaces represent a
formidable challenge because a large variety of molecular and dissociated water
species are present at the surface. Here, we present a comprehensive theoretical
analysis of the anharmonic OH stretching vibrations at the water/ZnO(101-0)
interface as a prototypical case. Molecular dynamics simulations employing a
reactive high-dimensional neural network potential based on density functional
theory calculations have been used to sample the interfacial structures. In the
second step, one-dimensional potential energy curves have been generated for a
large number of configurations to solve the nuclear Schrodinger equation. We find
that (i) the ZnO surface gives rise to OH frequency shifts up to a distance of
about 4 A from the surface; (ii) the spectrum contains a number of overlapping
signals arising from different chemical species, with the frequencies decreasing
in the order nu(adsorbed hydroxide) > nu(non-adsorbed water) > nu(surface
hydroxide) > nu(adsorbed water); (iii) stretching frequencies are strongly
influenced by the hydrogen bond pattern of these interfacial species. Finally, we
have been able to identify substantial correlations between the stretching
frequencies and hydrogen bond lengths for all species.
PMID- 29960341
TI - Accelerating atomic structure search with cluster regularization.
AB - We present a method for accelerating the global structure optimization of atomic
compounds. The method is demonstrated to speed up the finding of the anatase
TiO2(001)-(1 * 4) surface reconstruction within a density functional tight
binding theory framework using an evolutionary algorithm. As a key element of the
method, we use unsupervised machine learning techniques to categorize atoms
present in a diverse set of partially disordered surface structures into clusters
of atoms having similar local atomic environments. Analysis of more than 1000
different structures shows that the total energy of the structures correlates
with the summed distances of the atomic environments to their respective cluster
centers in feature space, where the sum runs over all atoms in each structure.
Our method is formulated as a gradient based minimization of this summed cluster
distance for a given structure and alternates with a standard gradient based
energy minimization. While the latter minimization ensures local relaxation
within a given energy basin, the former enables escapes from meta-stable basins
and hence increases the overall performance of the global optimization.
PMID- 29960342
TI - Gaussian approximation potential modeling of lithium intercalation in carbon
nanostructures.
AB - We demonstrate how machine-learning based interatomic potentials can be used to
model guest atoms in host structures. Specifically, we generate Gaussian
approximation potential (GAP) models for the interaction of lithium atoms with
graphene, graphite, and disordered carbon nanostructures, based on reference
density functional theory data. Rather than treating the full Li-C system, we
demonstrate how the energy and force differences arising from Li intercalation
can be modeled and then added to a (prexisting and unmodified) GAP model of pure
elemental carbon. Furthermore, we show the benefit of using an explicit pair
potential fit to capture "effective" Li-Li interactions and to improve the
performance of the GAP model. This provides proof-of-concept for modeling guest
atoms in host frameworks with machine-learning based potentials and in the longer
run is promising for carrying out detailed atomistic studies of battery
materials.
PMID- 29960343
TI - Effect of membrane tension on transbilayer movement of lipids.
AB - The stretching of plasma membranes of cells and lipid bilayers of vesicles
affects the physical properties of the membrane as well as the functions of
proteins/peptides in the membranes. Here, we examined the effect of membrane
tension on the rate constant of the transbilayer movement (kFF) of fluorescent
probe-labeled lipids using a new method. Specifically, we recently reported
[Hasan et al., Langmuir 34, 3349 (2018)] the development of a technique that
employs giant unilamellar vesicles (GUVs) with asymmetric lipid compositions in
two monolayers. In the present work, we found that the kFF greatly increased with
tension without leakage of water-soluble fluorescent probes from the GUV lumen
(i.e., without the formation of pores in the GUV membrane). We discussed the
plausible mechanisms for the effect of tension on the transbilayer movement of
lipids. As one of the mechanisms, we hypothesized that the transbilayer movement
of lipids occurs through the lateral diffusion of lipids in the walls of
hydrophilic pre-pores.
PMID- 29960344
TI - Time-lagged autoencoders: Deep learning of slow collective variables for
molecular kinetics.
AB - Inspired by the success of deep learning techniques in the physical and chemical
sciences, we apply a modification of an autoencoder type deep neural network to
the task of dimension reduction of molecular dynamics data. We can show that our
time-lagged autoencoder reliably finds low-dimensional embeddings for high
dimensional feature spaces which capture the slow dynamics of the underlying
stochastic processes-beyond the capabilities of linear dimension reduction
techniques.
PMID- 29960345
TI - Theoretical study of (e, 2e) triple differential cross sections of
tetrahydrofuran using multicenter distorted-wave method.
AB - We present in this work a theoretical study of the triple differential cross
sections for electron-impact single ionization of 12a' and 9b orbitals of a
tetrahydrofuran molecule. The calculations are performed by the multicenter
distorted-wave (MCDW) method in coplanar asymmetric kinematics with an incident
electron energy of 250 eV, where previous (e, 2e) experiments and theories are
available for comparison. The present calculations reproduce the experimental
measurements satisfactorily, indicating that the MCDW method can be easily
extended to study biomolecules with sufficiently high calculation efficiency.
PMID- 29960346
TI - Neural networks vs Gaussian process regression for representing potential energy
surfaces: A comparative study of fit quality and vibrational spectrum accuracy.
AB - For molecules with more than three atoms, it is difficult to fit or interpolate a
potential energy surface (PES) from a small number of (usually ab initio)
energies at points. Many methods have been proposed in recent decades, each
claiming a set of advantages. Unfortunately, there are few comparative studies.
In this paper, we compare neural networks (NNs) with Gaussian process (GP)
regression. We re-fit an accurate PES of formaldehyde and compare PES errors on
the entire point set used to solve the vibrational Schrodinger equation, i.e.,
the only error that matters in quantum dynamics calculations. We also compare the
vibrational spectra computed on the underlying reference PES and the NN and GP
potential surfaces. The NN and GP surfaces are constructed with exactly the same
points, and the corresponding spectra are computed with the same points and the
same basis. The GP fitting error is lower, and the GP spectrum is more accurate.
The best NN fits to 625/1250/2500 symmetry unique potential energy points have
global PES root mean square errors (RMSEs) of 6.53/2.54/0.86 cm-1, whereas the
best GP surfaces have RMSE values of 3.87/1.13/0.62 cm-1, respectively. When
fitting 625 symmetry unique points, the error in the first 100 vibrational levels
is only 0.06 cm-1 with the best GP fit, whereas the spectrum on the best NN PES
has an error of 0.22 cm-1, with respect to the spectrum computed on the reference
PES. This error is reduced to about 0.01 cm-1 when fitting 2500 points with
either the NN or GP. We also find that the GP surface produces a relatively
accurate spectrum when obtained based on as few as 313 points.
PMID- 29960347
TI - Fourier-transform-spectroscopic photoabsorption cross sections and oscillator
strengths for the S2 BSigmau-3-XSigmag-3 system.
AB - Photoabsorption cross sections and oscillator strengths for the strong,
predissociating vibrational bands, v >= 11, in the S2 BSigmau-3-XSigmag-3(v,0)
system are reported. Absorption measurements were undertaken on S2 vapor produced
by a radio-frequency discharge through H2S seeded in helium, and also in a two
temperature sulfur furnace, at temperatures of 370 K and 823 K, respectively. S2
column densities were determined in each source by combining experimental line
strengths in low-v non-predissociating B - X bands (v < 7) with calculated line f
values based on measured radiative lifetimes and calculated branching ratios. The
broad-band capabilities of two vacuum-ultraviolet Fourier-transform
spectrometers, used with instrumental resolutions of 0.22 cm-1 and 0.12 cm-1,
respectively, allowed for simultaneous recordings of both non-predissociating and
predissociating bands, thus placing the predissociating-band cross sections on a
common absolute scale. Uncertainties in the final cross section datasets are
estimated to be 15% for the 370-K vapor and 10% for the 823-K vapor. The
experimental cross sections are used to inform a detailed predissociation model
of the B(v) levels in Paper II [Lewis et al., J. Chem. Phys. 148, 244303 (2018)].
For astrophysical and other applications, this model can be adjusted simply to
provide isotopologue-specific cross sections for a range of relevant
temperatures.
PMID- 29960348
TI - Atomic diffusion in liquid nickel: First-principles modeling.
AB - Self- and impurity diffusion coefficients are assessed in the liquid nickel
system by the fundamental ab initio molecular dynamics approach. The impurity
diffusion coefficients in the Ni-X systems (X=C, Co, N, Nb, Ta, Ti, W) are mostly
not available in the current literature. The simulations are performed at four
temperatures, in the range from 1903 to 2303 K, which allows to extract
activation energies and frequency factors for the temperature dependent diffusion
coefficient assuming an Arrhenius-type behavior in the liquid. In addition to the
temperature dependence, the concentration-dependent impurity diffusion was
investigated for the Ni-Co system. The data are of relevance for the development
of the state-of-the art Ni-based superalloys and alternative binder systems in
cemented carbides. The obtained theoretical results are in very good agreement
with the limited experimental data for the diffusion in liquid Ni systems.
PMID- 29960349
TI - A local environment descriptor for machine-learned density functional theory at
the generalized gradient approximation level.
AB - We propose a grid-based local representation of electronic quantities that can be
used in machine learning applications for molecules, which is compact, fixed in
size, and able to distinguish different chemical environments. We apply the
proposed approach to represent the external potential in density functional
theory with modified pseudopotentials and demonstrate its proof of concept by
predicting the Perdew-Burke-Ernzerhof and local density approximation electronic
density and exchange-correlation potentials by kernel ridge regression. For 16
small molecules consisting of C, H, N, and O, the mean absolute error of exchange
correlation energy was 0.78 kcal/mol when trained for individual molecules.
Furthermore, the model is shown to predict the exchange-correlation energy with
an accuracy of 3.68 kcal/mol when the model is trained with a small fraction (4%)
of all 16 molecules of the present dataset, suggesting a promising possibility
that the current machine-learned model may predict the exchange-correlation
energies of an arbitrary molecule with reasonable accuracy when trained with a
sufficient amount of data covering an extensive variety of chemical environments.
PMID- 29960350
TI - Machine learning of molecular properties: Locality and active learning.
AB - In recent years, the machine learning techniques have shown great potent1ial in
various problems from a multitude of disciplines, including materials design and
drug discovery. The high computational speed on the one hand and the accuracy
comparable to that of density functional theory on another hand make machine
learning algorithms efficient for high-throughput screening through chemical and
configurational space. However, the machine learning algorithms available in the
literature require large training datasets to reach the chemical accuracy and
also show large errors for the so-called outliers-the out-of-sample molecules,
not well-represented in the training set. In the present paper, we propose a new
machine learning algorithm for predicting molecular properties that addresses
these two issues: it is based on a local model of interatomic interactions
providing high accuracy when trained on relatively small training sets and an
active learning algorithm of optimally choosing the training set that
significantly reduces the errors for the outliers. We compare our model to the
other state-of-the-art algorithms from the literature on the widely used
benchmark tests.
PMID- 29960351
TI - Alchemical and structural distribution based representation for universal quantum
machine learning.
AB - We introduce a representation of any atom in any chemical environment for the
automatized generation of universal kernel ridge regression-based quantum machine
learning (QML) models of electronic properties, trained throughout chemical
compound space. The representation is based on Gaussian distribution functions,
scaled by power laws and explicitly accounting for structural as well as
elemental degrees of freedom. The elemental components help us to lower the QML
model's learning curve, and, through interpolation across the periodic table,
even enable "alchemical extrapolation" to covalent bonding between elements not
part of training. This point is demonstrated for the prediction of covalent
binding in single, double, and triple bonds among main-group elements as well as
for atomization energies in organic molecules. We present numerical evidence that
resulting QML energy models, after training on a few thousand random training
instances, reach chemical accuracy for out-of-sample compounds. Compound datasets
studied include thousands of structurally and compositionally diverse organic
molecules, non-covalently bonded protein side-chains, (H2O)40-clusters, and
crystalline solids. Learning curves for QML models also indicate competitive
predictive power for various other electronic ground state properties of organic
molecules, calculated with hybrid density functional theory, including
polarizability, heat-capacity, HOMO-LUMO eigenvalues and gap, zero point
vibrational energy, dipole moment, and highest vibrational fundamental frequency.
PMID- 29960352
TI - Inclusion of nuclear quantum effects for simulations of nonlinear spectroscopy.
AB - The computation and interpretation of nonlinear vibrational spectroscopy is of
vital importance for understanding a wide range of dynamical processes in
molecular systems. Here, we introduce an approach to evaluate multi-time response
functions in terms of multi-time double symmetrized Kubo transformed thermal
correlation functions. Furthermore, we introduce a multi-time extension of ring
polymer molecular dynamics to evaluate these Kubo transforms. Benchmark
calculations show that the approximations are useful for short times even for
nonlinear operators, providing a consistent improvement over classical
simulations of multi-time correlation functions. The introduced methodology thus
provides a practical way of including nuclear quantum effects in multi-time
response functions of non-linear optical spectroscopy.
PMID- 29960353
TI - Less is more: Sampling chemical space with active learning.
AB - The development of accurate and transferable machine learning (ML) potentials for
predicting molecular energetics is a challenging task. The process of data
generation to train such ML potentials is a task neither well understood nor
researched in detail. In this work, we present a fully automated approach for the
generation of datasets with the intent of training universal ML potentials. It is
based on the concept of active learning (AL) via Query by Committee (QBC), which
uses the disagreement between an ensemble of ML potentials to infer the
reliability of the ensemble's prediction. QBC allows the presented AL algorithm
to automatically sample regions of chemical space where the ML potential fails to
accurately predict the potential energy. AL improves the overall fitness of
ANAKIN-ME (ANI) deep learning potentials in rigorous test cases by mitigating
human biases in deciding what new training data to use. AL also reduces the
training set size to a fraction of the data required when using naive random
sampling techniques. To provide validation of our AL approach, we develop the
COmprehensive Machine-learning Potential (COMP6) benchmark (publicly available on
GitHub) which contains a diverse set of organic molecules. Active learning-based
ANI potentials outperform the original random sampled ANI-1 potential with only
10% of the data, while the final active learning-based model vastly outperforms
ANI-1 on the COMP6 benchmark after training to only 25% of the data. Finally, we
show that our proposed AL technique develops a universal ANI potential (ANI-1x)
that provides accurate energy and force predictions on the entire COMP6
benchmark. This universal ML potential achieves a level of accuracy on par with
the best ML potentials for single molecules or materials, while remaining
applicable to the general class of organic molecules composed of the elements
CHNO.
PMID- 29960354
TI - Communication: Contact values of pair distribution functions in colloidal hard
disks by test-particle insertion.
AB - We apply Henderson's method for measuring the cavity distribution function y(r)
[J. Henderson, Mol. Phys. 48, 389 (1983)] to obtain the pair distribution
function at contact, g(sigma+). In contrast to the conventional distance
histogram method, no approximate extrapolation to contact is required. The
resulting equation of state from experiments and simulations of hard disks agrees
well with the scaled particle theory prediction up to high fluid packing
fractions. We also provide the first experimental measurement of y(r) inside the
hard core, which will allow for a more complete comparison with theory. The
method's flexibility is further illustrated by measuring the partial pair
distribution functions of binary hard-disk mixtures in simulation. The equation
for the contact values can be used to derive familiar results from statistical
geometry.
PMID- 29960355
TI - Predicting molecular properties with covariant compositional networks.
AB - Density functional theory (DFT) is the most successful and widely used approach
for computing the electronic structure of matter. However, for tasks involving
large sets of candidate molecules, running DFT separately for every possible
compound of interest is forbiddingly expensive. In this paper, we propose a
neural network based machine learning algorithm which, assuming a sufficiently
large training sample of actual DFT results, can instead learn to predict certain
properties of molecules purely from their molecular graphs. Our algorithm is
based on the recently proposed covariant compositional networks framework and
involves tensor reduction operations that are covariant with respect to
permutations of the atoms. This new approach avoids some of the representational
limitations of other neural networks that are popular in learning from molecular
graphs and yields promising results in numerical experiments on the Harvard Clean
Energy Project and QM9 molecular datasets.
PMID- 29960356
TI - An efficient water force field calibrated against intermolecular THz and Raman
spectra.
AB - A polarizable water model is presented which has been calibrated against
experimental THz and Raman spectra of bulk water. These low-frequency spectra
directly probe the dynamics, and thereby intermolecular interactions, on time
scales relevant to molecular motions. The model is based on the TL4P force field
developed recently by Tavan and co-workers [J. Phys. Chem. B 117, 9486 (2013)],
which has been designed to be transferable between different environments; in
particular, to correctly describe the electrostatic properties of both the
isolated water molecule in the gas-phase and the liquid water at ambient
conditions. Following this design philosophy, TL4P was amended with charge
transfer across hydrogen-bonded dimers as well as an anisotropic polarizability
in order to correctly reproduce the THz and Raman spectra. The thermodynamic and
structural properties of the new model are of equal quality as those of TL4P, and
at the same time, an almost quantitative agreement with the spectroscopic data
could be achieved. Since TL4P is a rigid model with a single polarizable site, it
is computationally very efficient, while the numerical overhead for the addition
of charge transfer and the anisotropic polarizability is minor. Overall, the
model is expected to be well suited for, e.g., large scale simulations of 2D
Raman-THz spectra or biomolecular simulations.
PMID- 29960357
TI - Compositional descriptor-based recommender system for the materials discovery.
AB - Structures and properties of many inorganic compounds have been collected
historically. However, it only covers a very small portion of possible inorganic
crystals, which implies the presence of numerous currently unknown compounds. A
powerful machine-learning strategy is mandatory to discover new inorganic
compounds from all chemical combinations. Herein we propose a descriptor-based
recommender-system approach to estimate the relevance of chemical compositions
where crystals can be formed [i.e., chemically relevant compositions (CRCs)]. In
addition to data-driven compositional similarity used in the literature, the use
of compositional descriptors as a prior knowledge is helpful for the discovery of
new compounds. We validate our recommender systems in two ways. First, one
database is used to construct a model, while another is used for the validation.
Second, we estimate the phase stability for compounds at expected CRCs using
density functional theory calculations.
PMID- 29960358
TI - Machine learning-based screening of complex molecules for polymer solar cells.
AB - Polymer solar cells admit numerous potential advantages including low energy
payback time and scalable high-speed manufacturing, but the power conversion
efficiency is currently lower than for their inorganic counterparts. In a Phenyl
C_61-Butyric-Acid-Methyl-Ester (PCBM)-based blended polymer solar cell, the
optical gap of the polymer and the energetic alignment of the lowest unoccupied
molecular orbital (LUMO) of the polymer and the PCBM are crucial for the device
efficiency. Searching for new and better materials for polymer solar cells is a
computationally costly affair using density functional theory (DFT) calculations.
In this work, we propose a screening procedure using a simple string
representation for a promising class of donor-acceptor polymers in conjunction
with a grammar variational autoencoder. The model is trained on a dataset of 3989
monomers obtained from DFT calculations and is able to predict LUMO and the
lowest optical transition energy for unseen molecules with mean absolute errors
of 43 and 74 meV, respectively, without knowledge of the atomic positions. We
demonstrate the merit of the model for generating new molecules with the desired
LUMO and optical gap energies which increases the chance of finding suitable
polymers by more than a factor of five in comparison to the randomised search
used in gathering the training set.
PMID- 29960359
TI - Size-independent neural networks based first-principles method for accurate
prediction of heat of formation of fuels.
AB - Neural network-based first-principles method for predicting heat of formation
(HOF) was previously demonstrated to be able to achieve chemical accuracy in a
broad spectrum of target molecules [L. H. Hu et al., J. Chem. Phys. 119, 11501
(2003)]. However, its accuracy deteriorates with the increase in molecular size.
A closer inspection reveals a systematic correlation between the prediction error
and the molecular size, which appears correctable by further statistical
analysis, calling for a more sophisticated machine learning algorithm. Despite
the apparent difference between simple and complex molecules, all the essential
physical information is already present in a carefully selected set of small
molecule representatives. A model that can capture the fundamental physics would
be able to predict large and complex molecules from information extracted only
from a small molecules database. To this end, a size-independent, multi-step
multi-variable linear regression-neural network-B3LYP method is developed in this
work, which successfully improves the overall prediction accuracy by training
with smaller molecules only. And in particular, the calculation errors for larger
molecules are drastically reduced to the same magnitudes as those of the smaller
molecules. Specifically, the method is based on a 164-molecule database that
consists of molecules made of hydrogen and carbon elements. 4 molecular
descriptors were selected to encode molecule's characteristics, among which raw
HOF calculated from B3LYP and the molecular size are also included. Upon the size
independent machine learning correction, the mean absolute deviation (MAD) of the
B3LYP/6-311+G(3df,2p)-calculated HOF is reduced from 16.58 to 1.43 kcal/mol and
from 17.33 to 1.69 kcal/mol for the training and testing sets (small molecules),
respectively. Furthermore, the MAD of the testing set (large molecules) is
reduced from 28.75 to 1.67 kcal/mol.
PMID- 29960360
TI - Unitary coupled-cluster based self-consistent polarization propagator theory: A
third-order formulation and pilot applications.
AB - In this article, the development of a third-order self-consistent polarization
propagator method based on unitary coupled-cluster (UCC) parametrization of the
ground-state wavefunction and the excitation manifold comprising unitary
transformed excitation operators, hereafter referred to as UCC3, is reported. The
UCC3 method is designed to provide excitation energies correct up to the third
order for excited states dominated by single excitations. An expansion for the
UCC transformed Hamiltonian involving Bernoulli numbers as expansion coefficients
is adopted in the derivation of UCC3 working equations. Interestingly, UCC-based
polarization propagator theory offers an alternative derivation for the strict
version of the third-order algebraic diagrammatic construction [ADC(3)-s] method.
The UCC3 results for the excitation energies of excited states in H2O, HF, N2,
Ne, CH2, BH, and C2 molecules are compared with benchmark full configuration
interaction values as well as ADC(3) and equation-of-motion coupled-cluster
singles and doubles results to demonstrate the accuracy of the UCC3 method. UCC
based self-consistent polarization propagator theory appears to be a promising
framework for developing non-perturbative hermitian formulations for treating
electronically excited states.
PMID- 29960361
TI - Constant size descriptors for accurate machine learning models of molecular
properties.
AB - Two different classes of molecular representations for use in machine learning of
thermodynamic and electronic properties are studied. The representations are
evaluated by monitoring the performance of linear and kernel ridge regression
models on well-studied data sets of small organic molecules. One class of
representations studied here counts the occurrence of bonding patterns in the
molecule. These require only the connectivity of atoms in the molecule as may be
obtained from a line diagram or a SMILES string. The second class utilizes the
three-dimensional structure of the molecule. These include the Coulomb matrix and
Bag of Bonds, which list the inter-atomic distances present in the molecule, and
Encoded Bonds, which encode such lists into a feature vector whose length is
independent of molecular size. Encoded Bonds' features introduced here have the
advantage of leading to models that may be trained on smaller molecules and then
used successfully on larger molecules. A wide range of feature sets are
constructed by selecting, at each rank, either a graph or geometry-based feature.
Here, rank refers to the number of atoms involved in the feature, e.g., atom
counts are rank 1, while Encoded Bonds are rank 2. For atomization energies in
the QM7 data set, the best graph-based feature set gives a mean absolute error of
3.4 kcal/mol. Inclusion of 3D geometry substantially enhances the performance,
with Encoded Bonds giving 2.4 kcal/mol, when used alone, and 1.19 kcal/mol, when
combined with graph features.
PMID- 29960362
TI - Conformation and dynamics of flexible polyelectrolytes in semidilute salt-free
solutions.
AB - We present steady shear rheology data for sodium polystyrene sulfonate (NaPSS) in
semidilute unentangled salt-free aqueous solution as a function of polymer
concentration (c) and degree of polymerisation (N). The measured terminal modulus
(G) agrees with the scaling prediction of G ? kBTc/N. The specific viscosity
varies with the degree of polymerisation as etasp ? N1.24+/-0.08. The observed
dependence differs with the linear relation expected from the Rouse model for
ideal chains as predicted by de Gennes' scaling model and subsequent theories.
Together with the diffusion data of Oostwal et al., our results suggest that
chains may follow non-Gaussian statistics beyond the correlation length (xi).
Small angle neutron scattering data on salt-free semidilute solutions at low
polymer concentrations partially support this hypothesis but do not confirm it.
The electrostatic Kuhn length of NaPSS salt-free solutions is found to be
proportional and slightly larger than the correlation length (LK,e ? 1.3xi). This
result agrees well with the scaling model of Dobrynin et al. Radii of gyration
(Rg) data as a function of polymer concentration reveal that a concentrated
regime (Rg ? c0) does not occur for NaPSS in the concentration range considered
(c ? 4M). We conclude by comparing the predictions of the scaling model of
Dobrynin et al. and Muthukumar's double screening theory with viscosity data for
different polyelectrolyte-solvent systems. Dobrynin's model provides a better
description of experimental observations. Our findings confirm several aspects of
current models for polyelectrolyte solutions but some deviations from theory
remain.
PMID- 29960363
TI - Large-scale ab initio calculations of Raman scattering spectra within time
dependent density functional perturbation theory.
AB - We develop an ab initio approach for large-scale Raman scattering spectra
simulations based on time-dependent density functional theory in conjunction with
the plane-wave pseudopotential method at the Gamma point. A Lagrangian functional
is introduced to analytically compute the first-order derivatives of the
frequency dependent polarizability with respect to nuclear coordinates. The
computational effort of Raman intensities required by our method is reduced by
one power of system size compared to that required for phonon frequency
calculations. The method is validated for several molecular and solid systems
including CH4, C2H2, C6H6, C60, bulk Si, and boron doped Si crystal and exhibits
excellent agreements with the experimental Raman spectra. We show that the method
yields a computational scaling of Ne2, with Ne ranging from 32 to 4000 electrons,
opening doors for many large-scale Raman spectra computations that are beyond the
reach of previous approaches.
PMID- 29960364
TI - Predissociation of the B Sigmau-3 state of S2: A coupled-channel model.
AB - A coupled-channel Schrodinger equation model of predissociation in the B Sigmau-3
state of S2 is developed and optimized by comparison with recent photoabsorption
spectra of the B Sigmau-3-X Sigmag-3(v,0) bands for 11 <= v <= 27, covering the
energy range 35 800-41 500 cm-1. All bands in this range exhibit varying degrees
of diffuseness, with corresponding predissociation linewidths Gamma ~ 4-60 cm-1
full-width at half-maximum. Model comparisons with both low-temperature (T = 370
K) and high-temperature (T = 823 K) spectra indicate, for many bands, significant
dependence of the linewidth on both the rotational quantum number J and the fine
structure component Fi. Just as in the analogous case of O2, the B(v)-state
predissociation in S2 is caused principally by spin-orbit interaction with 3Piu,
1Piu, 5Piu, and Sigmau+3 states. The inner-limb crossing with B"3Piu is
responsible for the predissociation of B(v = 11) and provides a significant
slowly varying contribution for B(v >= 12). The outer crossings with the 1Piu,
5Piu, and 2 Sigmau+3 states are responsible for oscillatory contributions to the
predissociation widths, with first peaks at v = 13, 20, and 24, respectively, and
the 5Piu contribution dominant. Prior to the photodissociation imaging study of
Frederix et al. [J. Phys. Chem. A 113, 14995 (2009)], which redefined the
dissociation energy of S2, the prevailing paradigm was that only the 1Piu
interaction was responsible for the B(v = 11-16) predissociation: this view is
not supported by our model.
PMID- 29960365
TI - Solid harmonic wavelet scattering for predictions of molecule properties.
AB - We present a machine learning algorithm for the prediction of molecule properties
inspired by ideas from density functional theory (DFT). Using Gaussian-type
orbital functions, we create surrogate electronic densities of the molecule from
which we compute invariant "solid harmonic scattering coefficients" that account
for different types of interactions at different scales. Multilinear regressions
of various physical properties of molecules are computed from these invariant
coefficients. Numerical experiments show that these regressions have near state
of-the-art performance, even with relatively few training examples. Predictions
over small sets of scattering coefficients can reach a DFT precision while being
interpretable.
PMID- 29960366
TI - Influence of weak reversible cross-linkers on entangled polymer melt dynamics.
AB - In this paper, we study a system of entangled chains that bear reversible cross
links in a melt state. The cross-links are tethered uniformly on the backbone of
each chain. A slip-link type model for the system is presented and solved for the
relaxation modulus. The effects of entanglements and reversible cross-linkers are
modelled as a discrete form of constraints that influence the motion of the
primitive path. In contrast to a non-associating entangled system, the model
calculations demonstrate that the elastic modulus has a much higher first plateau
and a delayed terminal relaxation. These effects are attributed to the evolution
of the entangled chains, as influenced by tethered reversible linkers. The model
is solved for the case when the linker survival time taus is greater than the
entanglement time taue, but less than the Rouse time tauR.
PMID- 29960367
TI - Enhancement of reaction rate in small-sized droplets: A combined analytical and
simulation study.
AB - Several recent mass spectrometry experiments reveal a marked enhancement of the
reaction rate of organic reactions in microdroplets. This enhancement has been
tentatively attributed to the accumulation of excess charge on a surface, which
in turn can give rise to a lowering of activation energy of the reaction. Here we
model the reactions in droplets as a three-step process: (i) diffusion of a
reactant from the core of the droplet to the surface, (ii) search by diffusion of
the reactant on the surface to find a reactive partner, and finally (iii) the
intrinsic reaction leading to bond breaking and product formation. We obtain
analytic expressions for the mean search time (MST) to find a target located on
the surface by a reactant in both two- and three-dimensional droplets. Analytical
results show quantitative agreement with Brownian dynamics simulations. We find,
as also reported earlier, that the MST varies as R2/D, where R is the radius of
the droplet and D is the diffusion constant of the molecules in the droplet
medium. We also find that a hydronium ion in the vicinity can substantially
weaken the bond and hence lowers the activation barrier. We observe a similar
facilitation of bond breaking in the presence of a static dipolar electric field
along any of the three Cartesian axes. If the intrinsic reaction is faster
compared to the mean search time involved, it becomes primarily a diffusion
controlled process; otherwise the reaction cannot be accelerated in the droplet
medium. The air-droplet interface provides a different environment compared to
the interior of the droplet. Hence, we might also expect a completely different
mechanism and products in the case of droplet reactions.
PMID- 29960368
TI - Automatic selection of atomic fingerprints and reference configurations for
machine-learning potentials.
AB - Machine learning of atomic-scale properties is revolutionizing molecular
modeling, making it possible to evaluate inter-atomic potentials with first
principles accuracy, at a fraction of the costs. The accuracy, speed, and
reliability of machine learning potentials, however, depend strongly on the way
atomic configurations are represented, i.e., the choice of descriptors used as
input for the machine learning method. The raw Cartesian coordinates are
typically transformed in "fingerprints," or "symmetry functions," that are
designed to encode, in addition to the structure, important properties of the
potential energy surface like its invariances with respect to rotation,
translation, and permutation of like atoms. Here we discuss automatic protocols
to select a number of fingerprints out of a large pool of candidates, based on
the correlations that are intrinsic to the training data. This procedure can
greatly simplify the construction of neural network potentials that strike the
best balance between accuracy and computational efficiency and has the potential
to accelerate by orders of magnitude the evaluation of Gaussian approximation
potentials based on the smooth overlap of atomic positions kernel. We present
applications to the construction of neural network potentials for water and for
an Al-Mg-Si alloy and to the prediction of the formation energies of small
organic molecules using Gaussian process regression.
PMID- 29960369
TI - A simulation method for the phase diagram of complex fluid mixtures.
AB - The phase behavior of complex fluid mixtures is of continuing interest, but
obtaining the phase diagram from computer simulations can be challenging. In the
Gibbs ensemble method, for example, each of the coexisting phases is simulated in
a different cell, and ensuring the equality of chemical potentials of all
components requires the transfer of molecules from one cell to the other. For
complex fluids such as polymers, successful insertions are rare. An alternative
method is to simulate both coexisting phases in a single simulation cell, with an
interface between them. The challenge here is that the interface position moves
during the simulation, making it difficult to determine the concentration profile
and coexisting concentrations. In this work, we propose a new method for single
cell simulations that uses a spatial concentration autocorrelation function to
(spatially) align instantaneous concentration profiles from different snapshots.
This allows one to obtain average concentration profiles and hence the coexisting
concentrations. We test the method by calculating the phase diagrams of two
systems: the Widom-Rowlinson model and the symmetric blends of freely jointed
polymer molecules for which phase diagrams from conventional methods are
available. Excellent agreement is found, except in the neighborhood of the
critical point where the interface is broad and finite size effects are
important. The method is easy to implement and readily applied to any mixture of
complex fluids.
PMID- 29960370
TI - Structural evolution and bonding properties of Au2Sin-/0 (n = 1-7) clusters:
Anion photoelectron spectroscopy and theoretical calculations.
AB - The photoelectron spectra of Au2Sin- (n = 1-7) clusters were measured, and the
structural evolution and bonding properties of Au2Si1-7- anions and their
corresponding neutral counterparts were investigated by theoretical calculations.
The two Au atoms in Au2Si1-7-/0 prefer to occupy low coordinate sites and form
fewer Au-Si bonds. The aurophilic interaction is fairly weak in these clusters.
The most stable structures of both Au2Sin- anions and Au2Sin neutrals can be
described as the two Au atoms interacting with the Sin frameworks. The most
stable isomers of Au2Sin- anions are in spin doublet states, while those of the
neutral clusters are in spin singlet states. The lowest-lying isomers of Au2Si1
/0 have C2v symmetric V-shaped structures. The global minimum of the Au2Si2-
anion has a D2h symmetric planar rhombus structure, while that of the Au2Si2
neutral adopts a C2v symmetric dibridged structure. In Au2Si3-/0, the two Au
atoms independently interact with the different Si-Si bonds of the Si3 triangular
structure. The global minima of Au2Si4-7-/0 primarily adopt prismatic based
geometries. Interestingly, Au2Si6-/0 have significant 3D aromaticity and possess
sigma plus pi double bonding characters, which play important roles in their
structural stability.
PMID- 29960371
TI - Predicting the stability of ternary intermetallics with density functional theory
and machine learning.
AB - We use a combination of machine learning techniques and high-throughput density
functional theory calculations to explore ternary compounds with the AB2C2
composition. We chose the two most common intermetallic prototypes for this
composition, namely, the tI10-CeAl2Ga2 and the tP10-FeMo2B2 structures. Our
results suggest that there may be ~10 times more stable compounds in these phases
than previously known. These are mostly metallic and non-magnetic. While the use
of machine learning reduces the overall calculation cost by around 75%, some
limitations of its predictive power still exist, in particular, for compounds
involving the second-row of the periodic table or magnetic elements.
PMID- 29960372
TI - wACSF-Weighted atom-centered symmetry functions as descriptors in machine
learning potentials.
AB - We introduce weighted atom-centered symmetry functions (wACSFs) as descriptors of
a chemical system's geometry for use in the prediction of chemical properties
such as enthalpies or potential energies via machine learning. The wACSFs are
based on conventional atom-centered symmetry functions (ACSFs) but overcome the
undesirable scaling of the latter with an increasing number of different elements
in a chemical system. The performance of these two descriptors is compared using
them as inputs in high-dimensional neural network potentials (HDNNPs), employing
the molecular structures and associated enthalpies of the 133 855 molecules
containing up to five different elements reported in the QM9 database as
reference data. A substantially smaller number of wACSFs than ACSFs is needed to
obtain a comparable spatial resolution of the molecular structures. At the same
time, this smaller set of wACSFs leads to a significantly better generalization
performance in the machine learning potential than the large set of conventional
ACSFs. Furthermore, we show that the intrinsic parameters of the descriptors can
in principle be optimized with a genetic algorithm in a highly automated manner.
For the wACSFs employed here, we find however that using a simple empirical
parametrization scheme is sufficient in order to obtain HDNNPs with high
accuracy.
PMID- 29960373
TI - Semi-local machine-learned kinetic energy density functional with third-order
gradients of electron density.
AB - A semi-local kinetic energy density functional (KEDF) was constructed based on
machine learning (ML). The present scheme adopts electron densities and their
gradients up to third-order as the explanatory variables for ML and the Kohn-Sham
(KS) kinetic energy density as the response variable in atoms and molecules.
Numerical assessments of the present scheme were performed in atomic and
molecular systems, including first- and second-period elements. The results of 37
conventional KEDFs with explicit formulae were also compared with those of the ML
KEDF with an implicit formula. The inclusion of the higher order gradients
reduces the deviation of the total kinetic energies from the KS calculations in a
stepwise manner. Furthermore, our scheme with the third-order gradient resulted
in the closest kinetic energies to the KS calculations out of the presented
functionals.
PMID- 29960374
TI - The potential for machine learning in hybrid QM/MM calculations.
AB - Hybrid quantum-mechanics/molecular-mechanics (QM/MM) simulations are popular
tools for the simulation of extended atomistic systems, in which the atoms in a
core region of interest are treated with a QM calculator and the surrounding
atoms are treated with an empirical potential. Recently, a number of atomistic
machine-learning (ML) tools have emerged that provide functional forms capable of
reproducing the output of more expensive electronic-structure calculations; such
ML tools are intriguing candidates for the MM calculator in QM/MM schemes. Here,
we suggest that these ML potentials provide several natural advantages when
employed in such a scheme. In particular, they may allow for newer, simpler QM/MM
frameworks while also avoiding the need for extensive training sets to produce
the ML potential. The drawbacks of employing ML potentials in QM/MM schemes are
also outlined, which are primarily based on the added complexity to the algorithm
of training and re-training ML models. Finally, two simple illustrative examples
are provided which show the power of adding a retraining step to such "QM/ML"
algorithms.
PMID- 29960375
TI - Building machine learning force fields for nanoclusters.
AB - We assess Gaussian process (GP) regression as a technique to model interatomic
forces in metal nanoclusters by analyzing the performance of 2-body, 3-body, and
many-body kernel functions on a set of 19-atom Ni cluster structures. We find
that 2-body GP kernels fail to provide faithful force estimates, despite
succeeding in bulk Ni systems. However, both 3- and many-body kernels predict
forces within an ~0.1 eV/A average error even for small training datasets and
achieve high accuracy even on out-of-sample, high temperature structures. While
training and testing on the same structure always provide satisfactory accuracy,
cross-testing on dissimilar structures leads to higher prediction errors, posing
an extrapolation problem. This can be cured using heterogeneous training on
databases that contain more than one structure, which results in a good trade-off
between versatility and overall accuracy. Starting from a 3-body kernel trained
this way, we build an efficient non-parametric 3-body force field that allows
accurate prediction of structural properties at finite temperatures, following a
newly developed scheme [A. Glielmo et al., Phys. Rev. B 95, 214302 (2017)]. We
use this to assess the thermal stability of Ni19 nanoclusters at a fractional
cost of full ab initio calculations.
PMID- 29960376
TI - Adsorption of molecular oxygen on the Ag(111) surface: A combined temperature
programmed desorption and scanning tunneling microscopy study.
AB - The adsorption of O2 on Ag(111) between 300 and 500 K has been studied with
temperature-programmed desorption (TPD) and scanning tunneling microscopy (STM).
At the first stage of adsorption, the disordered local oxide phase (commonly
looking in STM as an array of black spots) is formed on the surface irrespective
of the substrate temperature. The maximum concentration of black spots was found
to be ~0.11 ML, which corresponds to an oxygen coverage of ~0.66 ML. Taking into
account that the nucleation of the Ag(111)-p(4 * 4)-O phase starts after the
saturation of the disordered phase, one can conclude that its coverage is at
least not less than 0.66 ML. The analysis of STM and TPD data shows that the
thermodesorption peak (m/e = 32) at 570 K is related exclusively to the
decomposition of the p(4 * 4) phase, while the local oxide phase does not
contribute to desorption.
PMID- 29960377
TI - Metadynamics for training neural network model chemistries: A competitive
assessment.
AB - Neural network model chemistries (NNMCs) promise to facilitate the accurate
exploration of chemical space and simulation of large reactive systems. One
important path to improving these models is to add layers of physical detail,
especially long-range forces. At short range, however, these models are data
driven and data limited. Little is systematically known about how data should be
sampled, and "test data" chosen randomly from some sampling techniques can
provide poor information about generality. If the sampling method is narrow,
"test error" can appear encouragingly tiny while the model fails catastrophically
elsewhere. In this manuscript, we competitively evaluate two common sampling
methods: molecular dynamics (MD), normal-mode sampling, and one uncommon
alternative, Metadynamics (MetaMD), for preparing training geometries. We show
that MD is an inefficient sampling method in the sense that additional samples do
not improve generality. We also show that MetaMD is easily implemented in any
NNMC software package with cost that scales linearly with the number of atoms in
a sample molecule. MetaMD is a black-box way to ensure samples always reach out
to new regions of chemical space, while remaining relevant to chemistry near kbT.
It is a cheap tool to address the issue of generalization.
PMID- 29960378
TI - Analytic gradient and derivative couplings for the spin-flip extended
configuration interaction singles method: Theory, implementation, and application
to proton transfer.
AB - We present the formalism of analytic gradients and derivative couplings for the
spin-flip extended configuration interaction with single excitations (SF-XCIS)
method. We report an efficient implementation of the SF-XCIS method in the
framework of semiempirical quantum chemistry that allows fast excited-state
calculations for large systems. The performance of the SF-XCIS method in
combination with semiempirical orthogonalization-corrected models (OMx) is
statistically evaluated for vertical singlet excitation energies. The SF-XCIS
method treats the ground state and excited states in a fully balanced manner and
properly describes conical intersections involving the ground state. It can thus
be used in fewest switches surface hopping (FSSH) simulations of nonadiabatic
dynamics processes. This is demonstrated in an OM2/SF-XCIS FSSH pilot study of
excited-state proton transfer in 7-(2-pyridyl)indole.
PMID- 29960379
TI - The accuracy of ab initio calculations without ab initio calculations for charged
systems: Kriging predictions of atomistic properties for ions in aqueous
solutions.
AB - Using the machine learning method kriging, we predict the energies of atoms in
ion-water clusters, consisting of either Cl- or Na+ surrounded by a number of
water molecules (i.e., without Na+Cl- interaction). These atomic energies are
calculated following the topological energy partitioning method called
Interacting Quantum Atoms (IQAs). Kriging predicts atomic properties (in this
case IQA energies) by a model that has been trained over a small set of
geometries with known property values. The results presented here are part of the
development of an advanced type of force field, called FFLUX, which offers
quantum mechanical information to molecular dynamics simulations without the
limiting computational cost of ab initio calculations. The results reported for
the prediction of the IQA components of the energy in the test set exhibit an
accuracy of a few kJ/mol, corresponding to an average error of less than 5%, even
when a large cluster of water molecules surrounding an ion is considered. Ions
represent an important chemical system and this work shows that they can be
correctly taken into account in the framework of the FFLUX force field.
PMID- 29960380
TI - Fermi resonance in OH-stretch vibrational spectroscopy of liquid water and the
water hexamer.
AB - Vibrational spectroscopy of water contains a wealth of information about the
structure and dynamics of this fascinating substance. Theoretical modeling of
fundamental vibrational transitions in condensed water has proven difficult, and
in many circumstances, one cannot reach even qualitative agreement with
experiment. Due to the ability of water to form hydrogen bonds of various
strengths, the OH stretching band spans several hundreds of wave numbers in the
spectra, overlapping with the first overtone of the HOH bending band and
triggering a resonance between these two vibrations. This effect, known as Fermi
resonance, has been traditionally ignored in theoretical condensed-phase
simulations due to the additional computational burden and its deemed low
importance. Depending on a particular molecular environment, the Fermi resonance
manifests itself from small spectral features in the spectra of liquid water to
pronounced distinct peaks in the spectra of ice and water clusters. The goal of
this work is to illustrate the effects of including the Fermi resonance coupling
between the bending overtone and stretching fundamental vibrations in the mixed
quantum-classical formalism developed by Skinner and co-workers on the IR and
Raman spectra of liquid water and the water hexamer. We show that by adding the
Fermi resonance coupling, we are able to reproduce the location of the peak and a
shoulder on the red side of the IR spectrum as well as the bimodal structure of
the polarized Raman spectrum of liquid water at 300 K. Very good agreement
between theory and experiment is achieved for the IR spectra of the water hexamer
as well. We suggest that the Fermi resonance should not be ignored if intricate
features of spectra are of interest. In spite of these promising results obtained
in the region of a spectrum where Fermi resonance is important, further
development of spectroscopic maps is needed to improve agreement with the
experiment outside of the frequency range affected by the Fermi resonance.
PMID- 29960381
TI - Changes in political party systems arising from conflict and transfer among
political parties.
AB - Conflict that arises between two groups of different paradigms is an inevitable
phenomenon, and a representative example of the conflict among different groups
is a conflict phenomenon caused by competition among political parties. In this
paper, we study the dynamical behavior of a political party system. Considering
three major political parties, we investigate how political party systems can be
changed by employing a mathematical model. By considering the transfer mechanism
of recruitment as well as conflict of competition between political parties, we
found that all parties are likely to coexist when both the competition and
transfer between the parties are weak, or if either mechanism can occur at a
relatively low level. Otherwise, a political party system is changed to a single
party system. In addition, we found that when a party system was changed into a
single-party system, it appeared to be either bistable or multistable, and has
been elucidate by linear stability analysis. Our results may provide insights to
understand mechanisms how political party systems can be changed by conflict and
transfer.
PMID- 29960382
TI - Attractor reconstruction by machine learning.
AB - A machine-learning approach called "reservoir computing" has been used
successfully for short-term prediction and attractor reconstruction of chaotic
dynamical systems from time series data. We present a theoretical framework that
describes conditions under which reservoir computing can create an empirical
model capable of skillful short-term forecasts and accurate long-term ergodic
behavior. We illustrate this theory through numerical experiments. We also argue
that the theory applies to certain other machine learning methods for time series
prediction.
PMID- 29960383
TI - Resonance of scroll rings with periodic external fields in excitable media.
AB - By direct numerical simulations of a chemical reaction-diffusion system coupled
to a periodic external AC electric field with frequency equal to double frequency
of the scroll wave rotation, we find that scroll rings resonate with the electric
field and exhibit various dynamical behaviors, for example, their reversals,
collapses, or growths, depending both on the initial phase of AC electric fields
and on the initial phase of scroll rings. A kinematical model characterizing the
drift velocity of the scroll rings along their radial directions as well as that
of the scroll rings along their symmetry axes is proposed, which can effectively
account for the numerical observations and predict the behaviors of the scroll
rings. Besides, the existence of the equilibrium state of a scroll ring under the
AC electric fields is predicted by the kinematical model and the predictions
agree well with the simulations.
PMID- 29960384
TI - Influences of adding negative couplings between cliques of Kuramoto-like
oscillators.
AB - We study the dynamics in a clustered network of coupled oscillators by
considering positive and negative coupling schemes. Second order oscillators can
be interpreted as a model of consumers and generators working in a power network.
Numerical results indicate that coupling strategies play an important role in the
synchronizability of the clustered power network. It is found that the
synchronizability can be enhanced as the positive intragroup connections
increase. Meanwhile, when the intragroup interactions are positive and the
probability p that two nodes belonging to different clusters are connected is
increased, the synchronization has better performance. Besides, when the
intragroup connections are negative, it is observed that the power network has
poor synchronizability as the probability p increases. Our simulation results can
help us understand the collective behavior of the power network with positive and
negative couplings.
PMID- 29960385
TI - A Bayesian nonparametric approach to dynamical noise reduction.
AB - We propose a Bayesian nonparametric approach for the noise reduction of a given
chaotic time series contaminated by dynamical noise, based on Markov Chain Monte
Carlo methods. The underlying unknown noise process (possibly) exhibits heavy
tailed behavior. We introduce the Dynamic Noise Reduction Replicator model with
which we reconstruct the unknown dynamic equations and in parallel we replicate
the dynamics under reduced noise level dynamical perturbations. The dynamic noise
reduction procedure is demonstrated specifically in the case of polynomial maps.
Simulations based on synthetic time series are presented.
PMID- 29960386
TI - The emergence of multistability and chaos in a two-mode van der Pol generator
versus different connection types of linear oscillators.
AB - In this work, we study the multistability and chaos phenomena in a classical two
mode van der Pol generator which consists of a nonlinear element and two linear
oscillators. We show that the configuration of the connections of the linear
oscillators in the two-mode self-oscillating system significantly affects its
oscillation regimes and bifurcational transitions. In the case of the feedback
loop including one oscillator, the two-mode system demonstrates the well-known
effect of frequency entrainment, including bistability and hysteresis phenomena.
If the feedback loop involves both linear oscillators, the entrainment effect
disappears; however, two new complex regimes of quasi-periodicity and chaotic
self-oscillations emerge. We present here the results of the bifurcation analysis
of the multistability formation and transition to chaos.
PMID- 29960387
TI - Efficient disintegration strategies with cost constraint in complex networks: The
crucial role of nodes near average degree.
AB - The study of network disintegration, including controlling disease spread and
destroying terrorist organizations, has wide application scenarios and attracts
many researchers. In this paper, we concentrate on the network disintegration
problem with heterogeneous disintegration cost, where the disintegration cost to
eliminate each node might be non-identical. We first put forward a disintegration
cost model and an optimization model for disintegration strategy. Then, we
analyze the hub strategy, leaf strategy, and the average degree strategy to
investigate the nodes tendency of the optimal disintegration strategy. Numerical
experiments in three synthetic networks and real-world networks indicate that the
disintegration effect of hub strategy drops gradually when the disintegration
cost changes from homogeneity to heterogeneity. For the situation of strong
heterogeneity of disintegration cost of each node, average degree strategy
achieves the maximum disintegration effect gradually. Also, taking another
perspective, average degree strategy might enlighten efficient solutions to
protect critical infrastructure through strengthening the nodes which are chosen
by the average degree strategy.
PMID- 29960388
TI - Interactions of three-dimensional solitons in the cubic-quintic model.
AB - We report results of a systematic numerical analysis of interactions between
three-dimensional (3D) fundamental solitons, performed in the framework of the
nonlinear Schrodinger equation (NLSE) with the cubic-quintic (CQ) nonlinearity,
combining the self-focusing and defocusing terms. The 3D NLSE with the CQ terms
may be realized in terms of spatiotemporal propagation of light in nonlinear
optical media, and in Bose-Einstein condensates, provided that losses may be
neglected. The first part of the work addresses interactions between identical
fundamental solitons, with phase shift phi between them, separated by a finite
distance in the free space. The outcome strongly changes with the variation of
phi: in-phase solitons with phi = 0, or with sufficiently small phi, merge into a
single fundamental soliton, with weak residual oscillations in it (in contrast to
the merger into a strongly oscillating breather, which is exhibited by the 1D
version of the same setting), while the choice of phi = pi leads to fast
separation between mutually repelling solitons. At intermediate values of phi,
such as phi = pi/2, the interaction is repulsive too, breaking the symmetry
between the initially identical fundamental solitons, there appearing two
solitons with different total energies (norms). The symmetry-breaking effect is
qualitatively explained, similar to how it was done previously for 1D solitons.
In the second part of the work, a pair of fundamental solitons trapped in a 2D
potential is considered. It is demonstrated that they may form a slowly rotating
robust "molecule," if initial kicks are applied to them in opposite directions,
perpendicular to the line connecting their centers.
PMID- 29960389
TI - Detecting chaotic behaviors in dynamic complex social networks using a feature
diffusion-aware model.
AB - This paper contributes in detecting chaotic behaviors in dynamic complex social
networks using a new feature diffusion-aware model from two perspectives of
abnormal links as well as abnormal nodes. The proposed approach constructs a
probabilistic model of dynamic complex social networks and subsequently, applies
it to detect chaotic behaviors by measuring deviations from the model. The
predictive model considers the main processes of features' dynamics, evolution of
nodes' features, feature diffusion, and link generation processes in dynamic
complex social networks. The feature diffusion process indicates the process in
which each node former features influence the future features of its neighbors.
The proposed approach is validated by experiments on two real dynamic complex
social network datasets of Google+ and Twitter. The approach uses some Markov
Chain Monte Carlo sampling methods like Metropolis-Hastings algorithm and Slice
sampling strategy to extract the model parameters, given these real datasets.
Experimental results indicate the improved performance characteristics of the
proposed approach in comparison with baseline approaches in terms of the
performance measures of accuracy, F1-score, Matthews Correlation Coefficient,
recall, precision, area under ROC curve, and log-likelihood.
PMID- 29960390
TI - Symbolic recurrence plots to analyze dynamical systems.
AB - This paper, based on the concept of symbolic correlation integral, introduces a
set of symbolic recurrence plots and associated invariant measures, which are
independent of the distance parameter, serving as a tool for quantifying the
dynamic structure. These new measures allow the study of transient behavior,
coexistence of attractors, bifurcations, and structural change. The final user
does not have to choose the free distance parameter. An empirical application to
electrocardiography data illustrates the use of symbolic recurrence measures.
PMID- 29960391
TI - Apparent remote synchronization of amplitudes: A demodulation and interference
effect.
AB - A form of "remote synchronization" was recently described, wherein amplitude
fluctuations across a ring of non-identical, non-linear electronic oscillators
become entrained into spatially-structured patterns. According to linear models
and mutual information, synchronization and causality dip at a certain distance,
then recover before eventually fading. Here, the underlying mechanism is finally
elucidated through novel experiments and simulations. The system non-linearity is
found to have a dual role: it supports chaotic dynamics, and it enables the
energy exchange between the lower and higher sidebands of a predominant
frequency. This frequency acts as carrier signal in an arrangement resembling
standard amplitude modulation, wherein the lower sideband and the demodulated
baseband signals spectrally overlap. Due to a spatially-dependent phase
relationship, at a certain distance near-complete destructive interference occurs
between them, causing the observed dip. Methods suitable for detecting non
trivial entrainment, such as transfer entropy and the auxiliary system approach,
nevertheless, reveal that synchronization and causality actually decrease with
distance monotonically. Remoteness is, therefore, arguably only apparent, as also
reflected in the propagation of external perturbations. These results demonstrate
a complex mechanism of dynamical interdependence, and exemplify how it can lead
to incorrectly inferring synchronization and causality.
PMID- 29960393
TI - A variational method for analyzing limit cycle oscillations in stochastic hybrid
systems.
AB - Many systems in biology can be modeled through ordinary differential equations,
which are piece-wise continuous, and switch between different states according to
a Markov jump process known as a stochastic hybrid system or piecewise
deterministic Markov process (PDMP). In the fast switching limit, the dynamics
converges to a deterministic ODE. In this paper, we develop a phase reduction
method for stochastic hybrid systems that support a stable limit cycle in the
deterministic limit. A classic example is the Morris-Lecar model of a neuron,
where the switching Markov process is the number of open ion channels and the
continuous process is the membrane voltage. We outline a variational principle
for the phase reduction, yielding an exact analytic expression for the resulting
phase dynamics. We demonstrate that this decomposition is accurate over
timescales that are exponential in the switching rate epsilon-1. That is, we show
that for a constant C, the probability that the expected time to leave an O(a)
neighborhood of the limit cycle is less than T scales as T exp (-Ca/epsilon).
PMID- 29960394
TI - Phase walk analysis of leptokurtic time series.
AB - The Fourier phase information play a key role for the quantified description of
nonlinear data. We present a novel tool for time series analysis that identifies
nonlinearities by sensitively detecting correlations among the Fourier phases.
The method, being called phase walk analysis, is based on well established
measures from random walk analysis, which are now applied to the unwrapped
Fourier phases of time series. We provide an analytical description of its
functionality and demonstrate its capabilities on systematically controlled
leptokurtic noise. Hereby, we investigate the properties of leptokurtic time
series and their influence on the Fourier phases of time series. The phase walk
analysis is applied to measured and simulated intermittent time series, whose
probability density distribution is approximated by power laws. We use the day-to
day returns of the Dow-Jones industrial average, a synthetic time series with
tailored nonlinearities mimicing the power law behavior of the Dow-Jones and the
acceleration of the wind at an Atlantic offshore site. Testing for nonlinearities
by means of surrogates shows that the new method yields strong significances for
nonlinear behavior. Due to the drastically decreased computing time as compared
to embedding space methods, the number of surrogate realizations can be increased
by orders of magnitude. Thereby, the probability distribution of the test
statistics can very accurately be derived and parameterized, which allows for
much more precise tests on nonlinearities.
PMID- 29960392
TI - Is human atrial fibrillation stochastic or deterministic?-Insights from missing
ordinal patterns and causal entropy-complexity plane analysis.
AB - The mechanism of atrial fibrillation (AF) maintenance in humans is yet to be
determined. It remains controversial whether cardiac fibrillatory dynamics are
the result of a deterministic or a stochastic process. Traditional methods to
differentiate deterministic from stochastic processes have several limitations
and are not reliably applied to short and noisy data obtained during clinical
studies. The appearance of missing ordinal patterns (MOPs) using the Bandt-Pompe
(BP) symbolization is indicative of deterministic dynamics and is robust to brief
time series and experimental noise. Our aim was to evaluate whether human AF
dynamics is the result of a stochastic or a deterministic process. We used 38
intracardiac atrial electrograms during AF from the coronary sinus of 10 patients
undergoing catheter ablation of AF. We extracted the intervals between
consecutive atrial depolarizations (AA interval) and converted the AA interval
time series to their BP symbolic representation (embedding dimension 5, time
delay 1). We generated 40 iterative amplitude-adjusted, Fourier-transform (IAAFT)
surrogate data for each of the AA time series. IAAFT surrogates have the same
frequency spectrum, autocorrelation, and probability distribution with the
original time series. Using the BP symbolization, we compared the number of MOPs
and the rate of MOP decay in the first 1000 timepoints of the original time
series with that of the surrogate data. We calculated permutation entropy and
permutation statistical complexity and represented each time series on the causal
entropy-complexity plane. We demonstrated that (a) the number of MOPs in human AF
is significantly higher compared to the surrogate data (2.7 +/- 1.18 vs. 0.39 +/-
0.28, p < 0.001); (b) the median rate of MOP decay in human AF was significantly
lower compared with the surrogate data (6.58 * 10-3 vs. 7.79 * 10-3, p < 0.001);
and (c) 81.6% of the individual recordings had a rate of decay lower than the 95%
confidence intervals of their corresponding surrogates. On the causal entropy
complexity plane, human AF lay on the deterministic part of the plane that was
located above the trajectory of fractional Brownian motion with different Hurst
exponents on the plane. This analysis demonstrates that human AF dynamics does
not arise from a rescaled linear stochastic process or a fractional noise, but
either a deterministic or a nonlinear stochastic process. Our results justify the
development and application of mathematical analysis and modeling tools to enable
predictive control of human AF.
PMID- 29960395
TI - Analysis and generation of chaos using compositely connected coupled memristors.
AB - In large-scale high-density integrated circuits, memristors in close proximity to
one another both influence, and are influenced by, the behavior of nearby
memristors. However, the previous analyses of memristors-based circuit
applications have seldom considered the possibility of coupling effects between
memristors which invariably influences the response of all memristors, thus
rendering much previous research as incomplete. In this paper, the circuit
dynamics of memristive Chua's circuits are systematically analyzed based on a
pair of compositely connected flux-controlled memristors characterized by cubic
nonlinearity as a typical example. A theoretical analysis is undertaken and
verified via MATLAB. While tuning the coupling strength, variations in circuit
dynamics are characterized by phase portraits, bifurcation diagrams, and Lyapunov
exponents. A new floating memristor emulator with coupling ports, described by
cubic nonlinearity, is designed using off-the-shelf circuit devices and is shown
to be successfully used in building chaotic circuits in hardware experiments,
verifying theoretical results in simulations. This paper provides a new way
through which memristors-based circuit dynamics can be influenced by tuning the
coupling strength between memristors without changing other circuit parameters.
It is further highlighted that when designing future memristors-based circuits,
the coupling action between memristors should be considered if necessary and
compensated when causing undesired circuit responses.
PMID- 29960396
TI - The impact of individual heterogeneity on the coupled awareness-epidemic dynamics
in multiplex networks.
AB - Awareness of disease outbreaks can trigger changes in human behavior and has a
significant impact on the spread of epidemics. Previous studies usually
considered the coupled awareness-epidemic dynamics to be two competing processes
that interact in the information and epidemic layers. However, these studies
mostly assumed that all aware individuals have the same reduced infectivity and
that different neighbors have the same influence on one's perception, ignoring
the heterogeneity of individuals. In this paper, we propose a coupled awareness
epidemic spreading model in multiplex networks incorporating three types of
heterogeneity: (1) the heterogeneity of individual responses to disease
outbreaks, (2) the influence heterogeneity in the epidemic layer, and (3) the
influence heterogeneity in the information layer. The theoretical analysis shows
that the influence heterogeneity in the information layer has two-stage effects
on the epidemic threshold. Moreover, we find that the epidemic threshold in the
higher stage depends on the heterogeneity of individual responses and the
influence heterogeneity in the epidemic layer, while the epidemic threshold in
the lower stage is independent of awareness spreading and individual behaviors.
The results give us a better understanding of how individual heterogeneity
affects epidemic spreading and provide some practical implications for the
control of epidemics.
PMID- 29960397
TI - Gap-junction coupling can prolong beta-cell burst period by an order of magnitude
via phantom bursting.
AB - Pancreatic beta-cells show multiple intrinsic modes of oscillation with bursting
electrical activity playing a crucial role. Bursting is seen both in
experimentally isolated beta-cells as well as in electrically coupled cells in
the pancreatic islets, but the burst period is typically an order of magnitude
greater in coupled cells. This difference has previously been attributed to
noisier dynamics, or perturbed electrophysiological properties, in isolated beta
cells. Here, we show that diffusive coupling alone can extend the period more
than ten-fold in bursting oscillators modeled with a so-called phantom burster
model and analyze this result with slow-fast bifurcation analysis of an
electrically coupled pair of cells. Our results should be applicable to other
scenarios where coupling of bursting units, e.g., neurons, may increase the
oscillation period drastically.
PMID- 29960398
TI - Detection of traffic incidents using nonlinear time series analysis.
AB - In this study, we present results of the application of nonlinear time series
analysis on traffic data for incident detection. More specifically, we analyze
daily volume records of Attica Tollway (Greece) collected from sensors located at
various locations. The analysis was performed using the Recurrence Plot (RP) and
Recurrence Quantification Analysis (RQA) method of the volume data of the lane
closest to the median. The results show that it is possible to identify, through
the abrupt change of the dynamics of the system revealed by RPs and RQA, the
occurrence of incidents on the freeway and differentiate from recurrent traffic
congestion. The proposed methodology could be of interest for big data traffic
analysis.
PMID- 29960399
TI - Enhancing noise-induced switching times in systems with distributed delays.
AB - The paper addresses the problem of calculating the noise-induced switching rates
in systems with delay-distributed kernels and Gaussian noise. A general
variational formulation for the switching rate is derived for any distribution
kernel, and the obtained equations of motion and boundary conditions represent
the most probable, or optimal, path, which maximizes the probability of escape.
Explicit analytical results for the switching rates for small mean time delays
are obtained for the uniform and bi-modal (or two-peak) distributions. They
suggest that increasing the width of the distribution leads to an increase in the
switching times even for longer values of mean time delays for both examples of
the distribution kernel, and the increase is higher in the case of the two-peak
distribution. Analytical predictions are compared to the direct numerical
simulations and show excellent agreement between theory and numerical experiment.
PMID- 29960400
TI - Lagged multi-affine height correlation analysis for exploring lagged correlations
in complex systems.
AB - In order to analyze lagged correlations hidden in complex systems, we propose a
new method by incorporating a time-lagged operator into the multi-affine height
correlation analysis (MA-HCA). Application of this lagged MA-HCA to an
artificially simulated example indicates that the method is feasible to
successfully detect the existence of lagged correlations. We then apply this
method to explore lagged correlations in series arising from three real-world
complex systems.
PMID- 29960401
TI - Sparse identification of nonlinear dynamics for rapid model recovery.
AB - Big data have become a critically enabling component of emerging mathematical
methods aimed at the automated discovery of dynamical systems, where first
principles modeling may be intractable. However, in many engineering systems,
abrupt changes must be rapidly characterized based on limited, incomplete, and
noisy data. Many leading automated learning techniques rely on unrealistically
large data sets, and it is unclear how to leverage prior knowledge effectively to
re-identify a model after an abrupt change. In this work, we propose a conceptual
framework to recover parsimonious models of a system in response to abrupt
changes in the low-data limit. First, the abrupt change is detected by comparing
the estimated Lyapunov time of the data with the model prediction. Next, we apply
the sparse identification of nonlinear dynamics (SINDy) regression to update a
previously identified model with the fewest changes, either by addition,
deletion, or modification of existing model terms. We demonstrate this sparse
model recovery on several examples for abrupt system change detection in periodic
and chaotic dynamical systems. Our examples show that sparse updates to a
previously identified model perform better with less data, have lower runtime
complexity, and are less sensitive to noise than identifying an entirely new
model. The proposed abrupt-SINDy architecture provides a new paradigm for the
rapid and efficient recovery of a system model after abrupt changes.
PMID- 29960402
TI - Exponentially time decaying susceptible-informed (SIT) model for information
diffusion process on networks.
AB - Modeling information diffusion on networks is a timely topic due to its
significance in massive online social media platforms. Models motivated by
disease epidemics, such as the Susceptible-Infected-Removed and Susceptible
Infected-Susceptible (SIS), ones have been used for this task, together with
threshold models. A key limitation of these models is that the intrinsic time
value of information is not accounted for, an important feature for social media
applications, since "old" piece of news does not attract adequate attention. We
obtain results pertaining to the diffusion size across the diffusion's evolution
over time, as well as for early time points that enable us to calculate the phase
transition epoch and the epidemic threshold, using mean field approximations.
Further, we explicitly calculate the total probability of getting informed for
each node depending on its actual path to the single seed node and then propose a
novel approach by constructing a Maximum Weight Tree (MWT) to approximate the
final fraction of diffusion, with the weight of each node approximating the total
probability of getting informed. The MWT approximation is a novel approach that
is exact for tree-like network and is specifically designed for sparse networks.
It is also fast to compute and provides another general tool for the analyst to
obtain accurate approximations of the "epidemic's" size. Extensive comparisons
with results based on Monte Carlo simulation of the information diffusion process
show that the derived mean field approximations, as well as that employing the
MWT one, provide very accurate estimates of the quantities of interest.
PMID- 29960403
TI - Less can be more: How to make operations more flexible and robust with fewer
resources.
AB - We review empirical evidence from practice and general theoretical conditions,
under which simple rules of thumb can help to make operations flexible and
robust. An operation is flexible when it responds adaptively to adverse events
such as natural disasters; an operation is robust when it is less affected by
adverse events in the first place. We illustrate the relationship between
flexibility and robustness in the context of supply chain risk. In addition to
increasing flexibility and robustness, simple rules simultaneously reduce the
need for resources such as time, money, information, and computation. We
illustrate the simple-rules approach with an easy-to-use graphical aid for
diagnosing and managing supply chain risk. More generally, we recommend a four
step process for determining the amount of resources that decision makers should
invest in so as to increase flexibility and robustness.
PMID- 29960404
TI - Quantifying transient spreading dynamics on networks.
AB - Spreading phenomena on networks are essential for the collective dynamics of
various natural and technological systems, from information spreading in gene
regulatory networks to neural circuits and from epidemics to supply networks
experiencing perturbations. Still, how local disturbances spread across networks
is not yet quantitatively understood. Here, we analyze generic spreading dynamics
in deterministic network dynamical systems close to a given operating point.
Standard dynamical systems' theory does not explicitly provide measures for
arrival times and amplitudes of a transient spreading signal because it focuses
on invariant sets, invariant measures, and other quantities less relevant for
transient behavior. We here change the perspective and introduce formal
expectation values for deterministic dynamics to work out a theory explicitly
quantifying when and how strongly a perturbation initiated at one unit of a
network impacts any other. The theory provides explicit timing and amplitude
information as a function of the relative position of initially perturbed and
responding unit as well as depending on the entire network topology.
PMID- 29960405
TI - Synchronous high-frequency oscillations in inhibitory-dominant network motifs
consisting of three dentate gyrus-CA3 systems.
AB - Studies on the structural-functional connectomes of the human brain have
demonstrated the existence of synchronous firings in a specific brain network
motif. In particular, synchronization of high-frequency oscillations (HFOs) has
been observed in the experimental data sets of temporal lobe epilepsy (TLE). In
addition, both clinical and experimental evidences have accumulated to
demonstrate the effect of electrical stimulation on TLE, which, however, remains
largely unexplored. In this work, we first employ our previously proposed dentate
gyrus (DG)-CA3 network model to investigate the influence of an external
electrical stimulus on the HFO transitions. The results indicate that the
reinforcing stimulus can induce the HFO transitions of the DG-CA3 system from the
gamma band to the fast ripples band. Along with that, the consistent oscillations
of neurons within DG-CA3 can also be enhanced with the increasing of stimulus.
Then, we expand into a simple motif of three coupled DG-CA3 systems in both the
feedforward inhibition and feedback inhibition connections, to investigate the
synchronous evolutions of HFOs by regulating both the stimulation strength and
inhibitory function. It is shown that the comprehensive effects, which lead to
band transition, are independent of the motif configurations. The enhanced
external electrical stimulus weakens the synchronism and correlation of connected
motifs. In contrast, we demonstrate that the increased inhibitory coupling could
facilitate correlation to some extent. Overall, our work highlights the possible
origin of synchronous HFOs of hippocampal motifs governed by external inputs and
inhibitory connection, which might contribute to a better understanding of the
interplay between synchronization dynamics and epileptic structure in the human
brain.
PMID- 29960406
TI - On the emergence of critical regions at the onset of thermoacoustic instability
in a turbulent combustor.
AB - We use complex network theory to investigate the dynamical transition from stable
operation to thermoacoustic instability via intermittency in a turbulent
combustor with a bluff body stabilized flame. A spatial network is constructed,
representing each of these three dynamical regimes of combustor operation, based
on the correlation between time series of local velocity obtained from particle
image velocimetry. Network centrality measures enable us to identify critical
regions of the flow field during combustion noise, intermittency, and
thermoacoustic instability. We find that during combustion noise, the bluff body
wake turns out to be the critical region that determines the dynamics of the
combustor. As the turbulent combustor transitions to thermoacoustic instability,
during intermittency, the wake of the bluff body loses its significance in
determining the flow dynamics and the region on top of the bluff body emerges as
the most critical region in determining the flow dynamics during thermoacoustic
instability. The knowledge about this critical region of the reactive flow field
can help us devise optimal control strategies to evade thermoacoustic
instability.
PMID- 29960407
TI - Elementary fractal geometry. New relatives of the Sierpinski gasket.
AB - By slight modification of the data of the Sierpinski gasket, keeping the open set
condition fulfilled, we obtain self-similar sets with very dense parts, similar
to fractals in nature and in random models. This is caused by a complicated
structure of the open set and is revealed only under magnification. Thus, the
family of self-similar sets with separation condition is much richer and has
higher modelling potential than usually expected. An interactive computer search
for such examples and new properties for their classification are discussed.
PMID- 29960408
TI - Correlation in brain networks at different time scale resolution.
AB - Assessing brain connectivity makes up a major issue in the field of network
dynamics and neuroscience. Conventional experimental techniques are based on
functional imaging and magnetoencephalography, allowing to reconstruct the
activity of relatively small brain volume elements. A common approach to identify
networks consists in singling out sets of elements that maintain a correlated
activity over time. Despite the general consensus that these networks are
detectable on a time window of 10 s, no study is presently available on the
distribution and thus the reliability of this time scale. In this work, we
describe a new method to assess time scales on which correlations between network
elements occur and to consequently identify the underlying network structures.
The analysis relies on the evaluation of quasi-zero-delay cross-correlation
between power sequences associated with distinct volume elements. By changing the
width of the running window used to analyze successive segments of time series,
the behavior of cross-correlation at different time scales was investigated. The
onset of connectivity was estimated to be observable at about 30 s. The method
was applied to a set of volume elements that are supposed to belong to a known
resting-state network, namely the Default Mode Network. Fully connected networks
were identified, provided that a sufficiently long time scale is considered. Our
method makes up a new tool for the investigation of the temporal dynamics of
networks.
PMID- 29960409
TI - Chimera states and intermittency in an ensemble of nonlocally coupled Lorenz
systems.
AB - We study the spatiotemporal dynamics of coupled Lorenz systems with nonlocal
interaction and for small values of the coupling strength. It is shown that due
to the interaction the effective values of the control parameters can shift and
the classical quasi-hyperbolic Lorenz attractor in an isolated element is
transformed to a nonhyperbolic one. In this case, the network becomes multistable
that is a typical property of nonhyperbolic chaotic systems. This fact gives rise
to the appearance of chimera-like states, which have not been found in the
studied network before. We also reveal and describe three different types of
intermittency, both in time and in space, between various spatiotemporal
structures in the network of nonlocally coupled Lorenz models.
PMID- 29960410
TI - A mean-field game model for homogeneous flocking.
AB - Empirically derived continuum models of collective behavior among large
populations of dynamic agents are a subject of intense study in several fields,
including biology, engineering, and finance. We formulate and study a mean-field
game model whose behavior mimics an empirically derived nonlocal homogeneous
flocking model for agents with gradient self-propulsion dynamics. The mean-field
game framework provides a non-cooperative optimal control description of the
behavior of a population of agents in a distributed setting. In this description,
each agent's state is driven by optimally controlled dynamics that result in a
Nash equilibrium between itself and the population. The optimal control is
computed by minimizing a cost that depends only on its own state and a mean-field
term. The agent distribution in phase space evolves under the optimal feedback
control policy. We exploit the low-rank perturbative nature of the nonlocal term
in the forward-backward system of equations governing the state and control
distributions and provide a closed-loop linear stability analysis demonstrating
that our model exhibits bifurcations similar to those found in the empirical
model. The present work is a step towards developing a set of tools for
systematic analysis, and eventually design, of collective behavior of non
cooperative dynamic agents via an inverse modeling approach.
PMID- 29960411
TI - New fractional derivatives with non-singular kernel applied to the Burgers
equation.
AB - In this paper, we extend the model of the Burgers (B) to the new model of time
fractional Burgers (TFB) based on Liouville-Caputo (LC), Caputo-Fabrizio (CF),
and Mittag-Leffler (ML) fractional time derivatives, respectively. We utilize the
Homotopy Analysis Transform Method (HATM) to compute the approximate solutions of
TFB using LC, CF, and ML in the Liouville-Caputo sense. We study the convergence
analysis of HATM by computing the interval of the convergence, the residual error
function (REF), and the average residual error (ARE), respectively. The results
are very effective and accurate.
PMID- 29960412
TI - A 0.18-MUm CMOS high-data-rate true random bit generator through DeltaSigma
modulation of chaotic jerk circuit signals.
AB - A full-custom design of chaos-based True Random-Bit Generator (TRBG) implemented
on a 0.18-MUm CMOS technology is presented with unique composition of three major
components, i.e., (i) chaotic jerk oscillator, (ii) DeltaSigma modulator, and
(iii) simple pre/post-processing. A chaotic jerk oscillator is a deterministic
source of randomness that potentially offers robust and highly random chaotic
signals and exhibits a distinctive property of smoothly balanced-to-unbalanced
alternation of double-scroll attractors. The continuous-time 2nd-order DeltaSigma
modulator is introduced as a mixed-signal interface in order to increase a
resolution of random bit sequences while no extra clock is required. The
DeltaSigma modulator is constructed mainly by a folded-cascode amplifier with
sufficient gain and phase margin of 64 dB and 83 degrees , respectively, and a
high-speed comparator with a time constant of 2.7 ns. An uncomplicated structure
of shift-registers is realized as a post-processing process. The bit sequence of
the proposed TRBG successfully passes all statistical tests of NIST SP800-22 test
suite, and the ultimate output bit rate is 50 Mbps. The physical layout of a chip
area is 212.8 * 177.11 MUm and the DC power dissipation is 1.32mW using a 1.8-V
single supply voltage. This paper therefore offers a potential alternative to a
fully embedded cryptographic module in ASIC applications.
PMID- 29960413
TI - Flux bias-controlled chaos and extreme multistability in SQUID oscillators.
AB - The radio frequency (rf) Superconducting QUantum Interference Device (SQUID) is a
highly nonlinear oscillator exhibiting the rich dynamical behavior. It has been
studied for many years and it has found numerous applications in magnetic field
sensors, in biomagnetism, in non-destructive evaluation, and gradiometers, among
others. Despite its theoretical and practical importance, there is relatively
very little work on its multistability, chaotic properties, and bifurcation
structure. In the present work, the dynamical properties of the SQUID in the
strongly nonlinear regime are demonstrated using a well-established model whose
parameters lie in the experimentally accessible range of values. When driven by a
time-periodic (ac) flux either with or without a constant (dc) bias, the SQUID
exhibits extreme multistability at frequencies around the (geometric) resonance.
This effect is manifested by a "snake-like" form of the resonance curve. In the
presence of both ac and dc flux, multiple bifurcation sequences and secondary
resonance branches appear at frequencies above and below the geometric resonance.
In the latter case, the SQUID exhibits chaotic behavior in large regions of the
parameter space; it is also found that the state of the SQUID can be switched
from chaotic to periodic or vice versa by a slight variation of the dc flux.
PMID- 29960414
TI - Centrality in earthquake multiplex networks.
AB - Seismic time series has been mapped as a complex network, where a geographical
region is divided into square cells that represent the nodes and connections are
defined according to the sequence of earthquakes. In this paper, we map a seismic
time series to a temporal network, described by a multiplex network, and
characterize the evolution of the network structure in terms of the eigenvector
centrality measure. We generalize previous works that considered the single layer
representation of earthquake networks. Our results suggest that the multiplex
representation captures better earthquake activity than methods based on single
layer networks. We also verify that the regions with highest seismological
activities in Iran and California can be identified from the network centrality
analysis. The temporal modeling of seismic data provided here may open new
possibilities for a better comprehension of the physics of earthquakes.
PMID- 29960415
TI - Bistability in two simple symmetrically coupled oscillators with symmetry-broken
amplitude- and phase-locking.
AB - In the model system of two instantaneously and symmetrically coupled identical
Stuart-Landau oscillators, we demonstrate that there exist stable solutions with
symmetry-broken amplitude- and phase-locking. These states are characterized by a
non-trivial fixed phase or amplitude relationship between both oscillators, while
simultaneously maintaining perfectly harmonic oscillations of the same frequency.
While some of the surrounding bifurcations have been previously described, we
present the first detailed analytical and numerical description of these states
and present analytically and numerically how they are embedded in the bifurcation
structure of the system, arising both from the in-phase and the anti-phase
solutions, as well as through a saddle-node bifurcation. The dependence of both
the amplitude and the phase on parameters can be expressed explicitly with
analytic formulas. As opposed to the previous reports, we find that these
symmetry-broken states are stable, which can even be shown analytically. As an
example of symmetry-breaking solutions in a simple and symmetric system, these
states have potential applications as bistable states for switches in a wide
array of coupled oscillatory systems.
PMID- 29960416
TI - Lower bound of network dismantling problem.
AB - The network dismantling problem is one of the most fundamental problems in
network science. It aims to identify the minimum number of nodes, such that after
their removal the network is broken into many disconnected pieces with a sub
extensive size. However, the identification of the minimum removed nodes belongs
to the class of nondeterministic polynomial problems. Although many heuristic
algorithms have been proposed to identify the removed nodes, the smallest
dismantling set remains unknown. Therefore, the determination of a good lower
bound of dismantling sets is of great significance to evaluating the performances
of heuristic algorithms. The minimum number of deleted nodes to dismantle a
network is strictly no smaller than that to dismantle its any subnetwork in
nature. Any lower bound of a subnetwork is indeed a lower bound of the original
network. Utilizing the heterogeneous degree distribution and 2-core properties,
we find that with previous removal of some appropriate nodes, the lower bound
obtained on the basis of the subnetwork is counterintuitively significantly
better than the one obtained directly on the original network, especially for the
real-world networks.
PMID- 29960417
TI - Development of a clarity parameter using a time-varying loudness model.
AB - The perceived sound clarity is often estimated with the clarity index, which is
calculated on the basis of physical acoustic measures that can correlate weakly
to the way humans perceive sound for certain test conditions. Therefore, this
study proposes a clarity parameter based on a binaural room impulse response
processed with a time-varying loudness model. The proposed parameter is validated
by calculating the correlation coefficient with subject responses collected from
previous listening experiments. Results show that the parameter outperforms the
clarity index in most of the tested conditions, but its performance is less
robust than parameter for clarity (PCLA).
PMID- 29960418
TI - Computation of propagating and non-propagating guided modes in nonuniformly
stressed plates using spectral methods.
AB - This paper presents a numerical approach based on spectral methods for the
computation of guided ultrasonic wave modes (i.e., Lamb and shear horizontal) in
nonuniformly stressed plates. In particular, anisotropic elastic plates subjected
to a normal stress profile, which varies nonuniformly over their thickness, are
considered. The proposed approach computes the modeshapes and the full three
dimensional dispersion spectrum (i.e., real frequency, complex wavenumber). It
therefore includes both propagating (real wavenumber) and non-propagating
(complex wavenumber) modes. Furthermore, an approach for robustly post-processing
the dispersion spectra in order to compute the group velocity of propagating
modes is presented, which is based on a spectral quadrature method. Numerical
results are presented for two case studies: (1) a bending profile in a fiber
reinforced graphite/epoxy plate, and (2) an exponential profile in a silver
plate. The results show the computational efficiency (i.e., spectral convergence)
of the proposed method compared to other existing approaches such as the
sublayering and finite element methods.
PMID- 29960419
TI - Wideband compressive beamforming tomography for drive-by large-scale acoustic
source mapping.
AB - Noise-mapping is an effective sound visualization tool for the identification of
urban noise hotspots, which is crucial to taking targeted measures to tackle
environmental noise pollution. This paper develops a high-resolution wideband
acoustic source mapping methodology using a portable microphone array, where the
joint localization and power spectrum estimation of individual sources sparsely
distributed over a large region are achieved by tomographic imaging with the
multi-frequency delay-and-sum beamforming power outputs from multiple array
positions. Exploiting the fact that a wideband source has a common spatial signal
support across the frequency spectrum, two-dimensional tomographic maps are
produced by applying compressive sensing techniques including group least
absolute shrinkage selection operator formulation and sparse Bayesian learning to
promote group sparsity over multiple frequency bands. The high-resolution mapping
is demonstrated with experimental data recorded with a microphone array mounted
atop an electric vehicle driven along a road while playing audio clips from a
loudspeaker positioned within the adjacent open field.
PMID- 29960420
TI - Acoustic landmarks contain more information about the phone string than other
frames for automatic speech recognition with deep neural network acoustic model.
AB - Most mainstream automatic speech recognition (ASR) systems consider all feature
frames equally important. However, acoustic landmark theory is based on a
contradictory idea that some frames are more important than others. Acoustic
landmark theory exploits quantal nonlinearities in the articulatory-acoustic and
acoustic-perceptual relations to define landmark times at which the speech
spectrum abruptly changes or reaches an extremum; frames overlapping landmarks
have been demonstrated to be sufficient for speech perception. In this work,
experiments are conducted on the TIMIT corpus, with both Gaussian mixture model
(GMM) and deep neural network (DNN)-based ASR systems, and it is found that
frames containing landmarks are more informative for ASR than others. It is
discovered that altering the level of emphasis on landmarks by re-weighting
acoustic likelihood tends to reduce the phone error rate (PER). Furthermore, by
leveraging the landmark as a heuristic, one of the hybrid DNN frame dropping
strategies maintained a PER within 0.44% of optimal when scoring less than half
(45.8% to be precise) of the frames. This hybrid strategy outperforms other non
heuristic-based methods and demonstrate the potential of landmarks for reducing
computation.
PMID- 29960421
TI - Reconstruction of articulatory movements during neutral speech from those during
whispered speech.
AB - A transformation function (TF) that reconstructs neutral speech articulatory
trajectories (NATs) from whispered speech articulatory trajectories (WATs) is
investigated, such that the dynamic time warped (DTW) distance between the
transformed whispered and the original neutral articulatory movements is
minimized. Three candidate TFs are considered: an affine function with a diagonal
matrix ( Ad) which reconstructs one NAT from the corresponding WAT, an affine
function with a full matrix ( Af) and a deep neural network (DNN) based nonlinear
function which reconstruct each NAT from all WATs. Experiments reveal that the
transformation could be approximated well by Af, since it generalizes better
across subjects and achieves the least DTW distance of 5.20 (+/-1.27) mm (on
average), with an improvement of 7.47%, 4.76%, and 7.64% (relative) compared to
that with Ad, DNN, and the best baseline scheme, respectively. Further analysis
to understand the differences in neutral and whispered articulation reveals that
the whispered articulators exhibit exaggerated movements in order to reconstruct
the lip movements during neutral speech. It is also observed that among the
articulators considered in the study, the tongue exhibits a higher precision and
stability while whispering, implying that subjects control their tongue movements
carefully in order to render an intelligible whispered speech.
PMID- 29960423
TI - The acoustical signals produced by antibubble formation.
AB - An antibubble is an unusual object: a submerged water drop encapsulated in a thin
shell of air that is stable underwater for 10-100 s. They are often thought of as
the inverse of a soap bubble because they are a spherical shell of air in water
in contrast to a shell of water in air. Antibubbles may be formed when water
droplets impact the surface of surfactant-covered water, within a limited range
of drop radius and drop impact velocity. In this paper, the range of drop size
and impact velocity over which large antibubbles (radius 1-3 mm) are generated by
the impact of falling drops is characterised, and the relationship of these
parameters to the size of the antibubble formed is shown. Measurements of the two
acoustical signals that may be produced as an antibubble is formed by drop impact
are reported, and their relationship to the antibubble radius and shell thickness
is established. Acoustical measurements taken are interpreted in the context of a
modified Rayleigh-Plesset equation that provides a good fit to the frequency data
for air shells greater than 100 MUm in thickness. However, these results
highlight the need for future work on the damping mechanisms associated with
these larger antibubbles.
PMID- 29960422
TI - The influence of gas diffusion on bubble persistence in shock-scattering
histotripsy.
AB - Bubble cloud persistence reduces the efficacy of mechanical liquefaction with
shock-scattering histotripsy. In this study, the contribution of gas transfer to
bubble longevity was investigated in silico by solving the equations for bubble
oscillations and diffusion in parallel. The bubble gas content increased more
than 5 orders of magnitude during the expansion phase, arresting the inertial
collapse. The residual gas bubble required more than 15 ms for passive
dissolution post excitation, consistent with experimental observation. These
results demonstrate gas diffusion is an important factor in the persistence of
histotripsy-induced cavitation.
PMID- 29960424
TI - Multiple snapshot grid free compressive beamforming.
AB - Compressive sensing (CS) based estimation technique utilizes a sparsity promoting
constraint and solves the direction-of-arrival (DOA) estimation problem
efficiently with high resolution. In this paper a grid free CS based DOA
estimation technique is proposed, which uses sequential multiple snapshot data.
Conventional CS technique suffers from a basis mismatch issue, while grid free CS
technique is relieved of basis mismatch problem. Moreover, when the DOAs are
stationary, multiple snapshot processing provides stable estimates over
fluctuating single snapshot processing results. For multiple snapshot processing,
the generalized version of total variation norm (group total variation norm) is
implemented to impose a common sparsity pattern of multiple snapshot solution
vectors in a continuous angular domain. Furthermore, an extended version is
proposed using the singular value decomposition technique to mitigate
computational complexity resulting from a large number of multiple snapshots.
Data from SWellEx-96 are used to examine the proposed method. From the
experimental data, it was observed that the present method not only offers high
resolution even when the sources are coherent, but also the basis mismatch in the
conventional CS method can be avoided.
PMID- 29960425
TI - The influence of tonal categories and prosodic boundaries on the creakiness in
Mandarin.
AB - This study examines the distribution of creaky voice as a function of various
prosodic structures in a large-scale corpus of continuous speech of Mandarin.
Both tonal categories and prosodic boundaries have strong effects on the
likelihood of creak and relative creakiness. It was found that (1) creaky voice
in Mandarin is indeed largely driven by the occurrence of low pitch and
weakening; (2) Tone 3 sandhi and Tone 2 are different in both pitch and voice
quality; (3) the creakiness of Tone 3 (low tone) and the neutral tone (weakening)
is realized differently. Moreover, females and males do not differ in how they
use creaky voice linguistically.
PMID- 29960426
TI - Model-scale jet noise analysis with a single-point, frequency-domain nonlinearity
indicator.
AB - A single-point, frequency-domain nonlinearity indicator is calculated and
analyzed for noise from a model-scale jet at Mach 0.85, Mach 1.8, and Mach 2.0.
The nonlinearity indicator, nuN, has been previously derived from an ensemble
averaged, frequency-domain version of the generalized Burgers equation (GBE) from
Reichman, Gee, Neilsen, and Miller [J. Acoust. Soc. Am. 139, 2505-2513 (2016)].
The indicator gives the spatial rate of change due to nonlinear processes in
sound pressure level (SPL) spectrum, and two other indicators from the GBE-nuS
and nualpha-give the same quantity due to geometric spreading and absorption,
respectively. Trends with frequency, angle, distance, and jet condition-supported
both by spectral analysis and by calculation of the GBE-derived indicators-reveal
a concentration of nonlinear effects along radials close to the plume with large
overall SPLs. The calculated indicators for nonlinearity and absorption effects
far from the source combine to give the same decay predicted by nonlinear theory
for monofrequency sources. Trends in the nuN indicator are compared with trends
observed for other indicators such as pressure-derivative skewness and
bicoherence, revealing both the qualitative and quantitative advantages of the
nuN indicator.
PMID- 29960427
TI - Uncertainty of speech level parameters measured with a contact-sensor-based
device and a headworn microphone.
AB - This work estimates the uncertainty contributions of speech level parameters
measured with a contact-sensor-based device and a headworn microphone. Four
contributions are considered: (1) instrumental uncertainty, related to device
calibration; (2) method repeatability and (3) reproducibility, estimated through
repeated measurements without and with device repositioning, respectively; (4)
source reproducibility, due to the variability of human speech. To ascertain
changes in speech production, differences between measures should be at least
higher than the expanded uncertainty. In the case of device repositioning, the
expanded uncertainty combines contributions (1), (3), and (4). When the device is
not repositioned, it combines contributions (2) and (4).
PMID- 29960428
TI - Scattering of an arbitrary order acoustical Bessel beam by a rigid off-axis
spheroid.
AB - In this study, the authors use the partial-wave series expansion method in the
spherical coordinate system and provide a theoretical formula for the off-axis
acoustical scattering by rigid prolate and oblate spheroids illuminated by an
arbitrary-order Bessel beam to explore the physical characteristics of the off
axis far-field scattering (the axis of the Bessel beam is parallel to the axis of
the spheroids). The proposed method is verified and several three-dimensional far
field directivity patterns of rigid spheroids illuminated by zeroth- and first
order Bessel beams are depicted to explore the off-axis scattering. A special
emphasis is placed on the geometry size of the prolate and oblate spheroids, the
half-cone angle of the Bessel beam, the order of the Bessel beam, and the offset
position. Compared with the on-axis scattering, the derivation and calculation of
the off-axis scattering takes into account the spherical harmonic function using
a numerical integral procedure. In addition, no symmetry was observed in the
patterns of the far-field acoustic scattering form function for the zeroth- and
higher-order Bessel beams with the off-axis illumination. This investigation
provides a tool for the exploration of the complex scattering problems of
underwater non-spherical particles under the illumination of the Bessel beam.
PMID- 29960429
TI - Development of speech rhythm in first language: The role of syllable intensity
variability.
AB - The opening-closing alternations of the mouth were viewed as the articulatory
basis of speech rhythm. Such articulatory cycles have been observed to highly
correlate with the intensity curve of the speech signal. Analysis of the
intensity variability in English monolingual children and adults revealed that
(1) adults showed significantly smaller intensity variability than children, and
(2) intensity variability decreased from intermediate-aged children to older
children. Maturation of articulatory motor control is likely to be the main
reason for the reduced variability in articulatory cycles, and hence smaller
intensity variability in adults and older children.
PMID- 29960430
TI - Resolution enhancement of two-dimensional grid-free compressive beamforming.
AB - Reconstructing the acoustic source distribution via imposing a sparsity
constraint on a continuum, the atomic norm minimization (ANM) based grid-free
compressive beamforming can eliminate the basis mismatch of conventional grid
based compressive beamforming. However, it works well only for sufficiently
separated sources, which prohibits high resolution. The drawback arises because
it uses an atomic norm to measure the source sparsity, while the atomic norm is
not a direct sparse metric and its minimization is equivalent to the sparsity
constraint only when the sources are sufficiently separated. This paper devotes
itself to overcoming the drawback for the two-dimensional ANM based grid-free
compressive beamforming. First, a sparse metric that can promote sparsity to a
greater extent than the atomic norm is proposed. Then, using this metric a
minimization problem is formulated and the majorization-minimization (MM) solving
algorithm is introduced. MM iteratively conducts atomic norm minimization with a
sound reweighting strategy, and therefore the developed method can be termed as
iterative reweighted atomic norm minimization (IRANM). Both simulations and
experiments demonstrate that whether a standard uniform rectangular array or a
non-uniform array constituted by a small number of microphones is utilized, IRANM
can overcome the drawback and thus enhance the resolution.
PMID- 29960431
TI - Effects of ear canal occlusion on hearing sensitivity: A loudness experiment.
AB - Over the last century, hearing research has repeatedly reported differences in
loudness perception when different types of transducers are being used. One of
the effects of using different transducers is that listening may be performed via
an open ear (loudspeaker), a cushioned ear (headphones), or an occluded ear
(hearing aid receivers, insert earphones). The question of whether varying the
acoustic load applied to the ear canal might impact hearing sensitivity has
therefore become essential given the need to establish realistic noise damage
risk criteria in an attempt to prevent noise-induced hearing loss for any given
listening condition. Although such loudness discrepancies in the cushioned ear
have been recently proven to be caused by loudness measurement artifacts,
currently available data do not exclude a possible impact of ear canal occlusion
on loudness perception. This paper presents the results of a loudness balance
test carried out on 18 normal-hearing listeners. Using an earplug to occlude the
canal, in-ear sound pressure levels were compared between the occluded ear and
the cushioned ear at equal loudness. The results show agreement within 1 dB
between the two listening conditions, and support the conclusion that loudness
does not depend on the type of acoustic load applied to the ear canal.
PMID- 29960432
TI - Statistics on noise covariance matrix for covariance fitting-based compressive
sensing direction-of-arrival estimation algorithm: For use with optimization via
regularization.
AB - A covariance fitting algorithm for the estimation of direction-of-arrivals of
multiple incident signals is addressed in this paper. The scheme takes advantage
of the fact that the incident signals are spatially sparse. A previous study has
presented the regularization parameters of the covariance fitting for a very
large number of snapshots. In this paper, a strategy on how to determine the
regularization constant of the covariance fitting for a general number of
snapshots is presented. The strategy essentially exploits the norm of the noise
covariance matrix. The proposed algorithm has been validated via numerical
simulations.
PMID- 29960433
TI - Tuning a musical instrument with vibrato system: A mathematical framework to
study mechanics and acoustics and to calculate optimal tuning strategies.
AB - String instruments such as electric guitars are often equipped with a vibrato
system, which allows varying the pitch of all strings as a musical effect. It is
usually based on a mobile bridge that is kept in balance by the strings and a
coiled spring. Tuning such an instrument is complex, since adjusting the tension
on one string will alter all other strings' tensions. In practice, a heuristic
method is used where all strings are repeatedly tuned to the desired pitch, which
appears to reliably yield correct pitches after a while. It is unclear why this
method works; an analysis is lacking. This paper presents a mathematical model to
study this subject in detail; the model captures the underlying mechanics and
acoustics and can be used to simulate a typical tuning process. The paper then
verifies the model with experimental data and shows that the model permits
calculation of optimal tuning strategies that use the least number of adjustment
steps.
PMID- 29960434
TI - Learning to extract a large inter-aural level difference in lag clicks.
AB - Many blind people learn to use sound reflections to localize objects. However,
precedence-effect research has reported evidence both for and against the
possibility to improve lateralization of lag clicks preceded by lead clicks. This
training study used stimuli more relevant to human echolocation than did previous
training studies. One participant, the author, practiced lateralizing a lag-click
inter-aural level difference (ILD) of 10 dB for 60 days, with performance
measured in the lag-lead peak amplitude ratio at threshold. Clear improvements
were observed at interclick intervals of 2-18 ms, suggesting that extracting a
large lag-click ILD may improve with practice.
PMID- 29960435
TI - Using residential proximity to wind turbines as an alternative exposure measure
to investigate the association between wind turbines and human health.
AB - This analysis uses data from the Community Noise and Health Study developed by
Statistics Canada to investigate the association between residential proximity to
wind turbines and health-related outcomes in a dataset that also provides
objective measures of wind turbine noise. The findings indicate that residential
proximity to wind turbines is correlated with annoyance and health-related
quality of life measures. These associations differ in some respects from
associations with noise measurements. Results can be used to support discussions
between communities and wind-turbine developers regarding potential health
effects of wind turbines.
PMID- 29960436
TI - Spatial power spectral density estimation using a multitapered coprime sensor
array minimum processor.
AB - A coprime sensor array (CSA) is a sparse array geometry that interleaves two
spatially undersampled uniform linear arrays (ULAs) with coprime undersampling
factors. The CSA Min processor achieves an asymptotically unbiased spatial power
spectral density (PSD) estimate while approaching the variance of a ULA
conventional beamformer. Nonstationary underwater sonar environments often
preclude the number of snapshots required to achieve a desirable PSD variance.
The multitaper method improves PSD variance by O(K) at the expense of resolution
without additional snapshot cost by averaging uncorrelated PSD estimates obtained
using a set of K orthogonal tapers. This paper proposes the multitapered Min
processor to achieve unambiguous PSD estimates with desirable variance properties
for passive beamforming scenarios. The probability density function and the first
two moments of the MT-Min processor's PSD estimate are derived in closed-form for
spatially white Gaussian processes. Simulations verify the variance reduction
predicted by the analytical derivation for white processes and, by extension, for
non-white processes. The multitaper method is then extended to an ad hoc mixture
of Min and Product processors under constant noise plateau normalization that
attenuates the spurious peaks occurring in the CSA PSD estimates in the presence
of multiple planewave arrivals.
PMID- 29960437
TI - Diffuse-field reciprocity calibration of half-inch laboratory standard
microphones using simultaneous reverberation time measurement.
AB - This paper presents a procedure for diffuse-field calibration of half-inch
laboratory standard microphones by reciprocity using three microphones and a
small reverberation chamber. The procedure consists of obtaining the impulse
response of the system microphone-chamber-microphone and employing it to
determine both the electrical transfer impedance between the microphones and the
chamber's reverberation time (necessary to calculate the acoustic transfer
impedance between the microphones). The electrical transfer impedance is
calculated from the reverberant part of the obtained impulse response and the
reverberation time is obtained by integrating the same impulse response. A
comparison between results obtained by the proposed procedure (by the reciprocity
method) and pressure field results corrected to diffuse-field (an usual
alternative method) shows the accuracy of the proposal, while a comparison with
other diffuse-field procedures using the reciprocity method shows that the
measured frequency range is extended down, whereas similar performance is found
in the common range.
PMID- 29960438
TI - Multisensory stimuli improve relative localisation judgments compared to
unisensory auditory or visual stimuli.
AB - Observers performed a relative localisation task in which they reported whether
the second of two sequentially presented signals occurred to the left or right of
the first. Stimuli were detectability-matched auditory, visual, or auditory
visual signals and the goal was to compare changes in performance with
eccentricity across modalities. Visual performance was superior to auditory at
the midline, but inferior in the periphery, while auditory-visual performance
exceeded both at all locations. No such advantage was seen when performance for
auditory-only trials was contrasted with trials in which the first stimulus was
auditory-visual and the second auditory only.
PMID- 29960439
TI - Sequential adaptive elastic net approach for single-snapshot source localization.
AB - This paper proposes efficient algorithms for accurate recovery of direction-of
arrivals (DoAs) of sources from single-snapshot measurements using compressed
beamforming (CBF). In CBF, the conventional sensor array signal model is cast as
an underdetermined complex-valued linear regression model and sparse signal
recovery methods are used for solving the DoA finding problem. A complex-valued
pathwise weighted elastic net (c-PW-WEN) algorithm is developed that finds
solutions at the knots of penalty parameter values over a path (or grid) of
elastic net (EN) tuning parameter values. c-PW-WEN also computes least absolute
shrinkage and selection operator (LASSO) or weighted LASSO in its path. A
sequential adaptive EN (SAEN) method is then proposed that is based on c-PW-WEN
algorithm with adaptive weights that depend on previous solution. Extensive
simulation studies illustrate that SAEN improves the probability of exact
recovery of true support compared to conventional sparse signal recovery
approaches such as LASSO, EN, or orthogonal matching pursuit in several
challenging multiple target scenarios. The effectiveness of SAEN is more
pronounced in the presence of high mutual coherence.
PMID- 29960440
TI - Modeling of the multimodal radiation from an open-ended waveguide.
AB - The multimodal radiation from the open end of a cylindrical waveguide with
arbitrary wall thickness is solved by deriving algebraic solutions of the
radiation impedance matrix, without restrictive hypothesis on the frequency
range. The basic idea of the method is to turn the original unbounded problem
into the problem of a cylindrical waveguide embedded in an infinite waveguide
with an annular perfectly matched layer (PML) on its wall. Then, using a
multimodal formalism of the guided wave propagation and a complex coordinate
stretching PML, algebraic expressions are derived for the continuity and
radiation conditions in this coupled system.
PMID- 29960441
TI - Observations of wind-generated noise by the tropical cyclone.
AB - An analysis of the measured ocean noise during the tropical cyclone period is
presented. While the observed noise is highly correlated with wind, this study
reveals the dispersion of noise spectra. A wind-driven noise model within the
framework of the bubble oscillation is developed. The noise spectrum for
frequencies from hundreds of hertz to kilohertz due to the effective bubble
oscillation within the bubble cloud is assumed instead of the collective bubble
oscillation. The proposed model addresses the arbitrarily-shaped bubble clouds in
a stratified ocean and the relation between the wind speed and the noise level,
and these aspects develop from the existing models in the literature. The wind
driven ocean noise spectrum is estimated as a function of frequency and wind
speed based on available information of the bubble creation rate. The comparison
shows that the proposed model with optimized oceanographic parameters could fit
the noise spectra of data for the frequencies from about 0.5 to 4 kHz, which
indicates that the modified model based on the bubble oscillations within the
bubble clouds could account for the mechanism of wind-generated noise data.
PMID- 29960442
TI - Ultrasonic backscatter difference measurements of cancellous bone from the human
femur: Relation to bone mineral density and microstructure.
AB - Ultrasonic backscatter techniques are being developed to detect changes in
cancellous bone caused by osteoporosis. One technique, called the backscatter
difference technique, measures the power difference between two portions of a
backscatter signal. The goal of the present study is to investigate how bone
mineral density (BMD) and the microstructure of human cancellous bone influence
four backscatter difference parameters: the normalized mean of the backscatter
difference (nMBD) spectrum, the normalized slope of the backscatter difference
spectrum, the normalized intercept of the backscatter difference spectrum, and
the normalized backscatter amplitude ratio (nBAR). Ultrasonic measurements were
performed with a 3.5 MHz broadband transducer on 54 specimens of human cancellous
bone from the proximal femur. Volumetric BMD and the microstructural
characteristics of the specimens were measured using x-ray micro-computed
tomography. Of the four ultrasonic parameters studied, nMBD and nBAR demonstrated
the strongest univariate correlations with density and microstructure.
Multivariate analyses indicated that nMBD and nBAR depended on trabecular
separation and possibly other microstructural characteristics of the specimens
independently of BMD. These findings suggest that nMBD and nBAR may be sensitive
to changes in the density and microstructure of bone caused by osteoporosis.
PMID- 29960443
TI - Steady-state anti-plane shear wave scattering by a crack with friction.
AB - The present article describes the steady-state numerical modeling of anti-plane
shear wave scattering by a crack with frictional boundary conditions. The system
is composed of an unbounded elastic solid that includes a closed crack under
static compressive stress. A time-harmonic anti-plane shear wave is incident, and
dynamic friction between the crack faces is induced as a nonlinear phenomenon.
The anti-plane wave scattering can be described in a retarded potential integral
equation by taking the nonlinearity into account. The present article introduces
the steady-state expression as an asymptotic vibration of crack faces after a
sufficient elapsed time. In order to solve the equations describing nonlinear
steady-state vibration, a harmonic balance method is integrated into a boundary
element method. Fourier coefficients of crack opening displacement distributed on
the crack face are treated as unknown variables. The system of nonlinear
equations is solved by means of a numerical continuation method. The present
numerical results show almost complete agreement with those obtained by the
conventional time-domain analysis after a sufficient elapsed time. Furthermore,
the robustness and effectiveness of the proposed method are demonstrated
numerically.
PMID- 29960444
TI - A Legendre-Galerkin spectral method for constructing atmospheric acoustic normal
modes.
AB - A Legendre-Galerkin spectral method is applied to the construction of atmospheric
acoustic normal modes above level ground, represented by a complex impedance. A
search in the complex plane for modal eigenvalues is replaced by a complex
symmetric matrix eigenvalue problem. The Legendre-Galerkin spectral method
projects the acoustic normal modes onto an orthogonal basis of Legendre
polynomials. The matrix eigenvalue problem can be solved by readily available,
public domain, software. Prior knowledge of the location of a set of nearby real
eigenvalues is unnecessary since the complex symmetric matrix formulation
embodies an approximation of all of the physical constraints of the problem. The
normal modes are used to compute the acoustic field, due to a harmonic point
source in the atmosphere, including a group of discrete modes radiating into the
upper atmosphere, usually associated with the continuous spectrum. The validity
of the acoustic field calculation is tested in a comparison with the fast field
program and interpreted, with aid of the normal modes, in a downward-refracting
atmosphere.
PMID- 29960445
TI - Acoustic scattering from a cylindrical shell with an internal rigid plate:
Analysis and experiment.
AB - The sound scattering from a fluid-loaded stiffened cylindrical shell at normal
incidence is studied by theoretical and experimental approaches. The cylindrical
shell is reinforced by an internal longitudinal rigid plate attached to the shell
along the axial direction. The backscattered sound is analyzed via the frequency
angle spectra. By studying the generation, propagation, and radiation of the
waves, the authors found that the dominant features in the frequency-angle
spectra can be explained by the resonance of the shell and the interaction
between the scattered and radiation waves. The most significant effect of the
internal plate is the radiation of the subsonic a0 waves caused by the
attachments of the internal plate. Furthermore, simple formulas are given to
predict the interference fringes in the frequency-angle spectra due to the
interference between the specular reflection and the scattering from the shell
structure response.
PMID- 29960446
TI - Explaining intelligibility in speech-modulated maskers using acoustic glimpse
analysis.
AB - Intelligibility was measured in speech-modulated noise varying in level and
temporal modulation rate (TMR). Acoustic analysis measured glimpses available
above a local signal-to-noise ratio criterion (LC). The proportion and rate of
glimpses were correlated with intelligibility, particularly in relation to masker
level or TMR manipulations, respectively. Intelligibility correlations for each
metric were maximized at different analysis LCs. Regression analysis showed that
both metrics measured at -2 dB LC were required to best explain the total
variance (R2 = 0.49) for individual sentence intelligibility. Acoustic conditions
associated with recognizing speech in complex maskers are best explained using
multidimensional glimpse metrics.
PMID- 29960448
TI - Effect of pile-driving sounds on harbor seal (Phoca vitulina) hearing.
AB - Seals exposed to intense sounds may suffer hearing loss. After exposure to
playbacks of broadband pile-driving sounds, the temporary hearing threshold shift
(TTS) of two harbor seals was quantified at 4 and 8 kHz (frequencies of the
highest TTS) with a psychoacoustic technique. The pile-driving sounds had: a 127
ms pulse duration, 2760 strikes per h, a 1.3 s inter-pulse interval, a ~9.5% duty
cycle, and an average received single-strike unweighted sound exposure level
(SELss) of 151 dB re 1 MUPa2s. Exposure durations were 180 and 360 min
[cumulative sound exposure level (SELcum): 190 and 193 dB re 1 MUPa2s]. Control
sessions were conducted under low ambient noise. TTS only occurred after 360 min
exposures (mean TTS: seal 02, 1-4 min after sound stopped: 3.9 dB at 4 kHz and
2.4 dB at 8 kHz; seal 01, 12-16 min after sound stopped: 2.8 dB at 4 kHz and 2.6
dB at 8 kHz). Hearing recovered within 60 min post-exposure. The TTSs were small,
due to the small amount of sound energy to which the seals were exposed.
Biological TTS onset SELcum for the pile-driving sounds used in this study is
around 192 dB re 1 MUPa2s (for mean received SELss of 151 dB re 1 MUPa and a duty
cycle of ~9.5%).
PMID- 29960449
TI - Variability due to short-distance favorable sound propagation and its
consequences for immission assessment.
AB - The specific noise immission from an (industrial) noise source is commonly
assessed by short-term measurements. Good practice prescribes measuring under
downwind conditions at modest wind speeds. Nevertheless, this still leads to
large variation, even at short distances and needs quantification. More
specifically, the variation in sound propagation due to the changing refractive
state of the atmosphere and the relatively large variation in soil impedance one
can find for (visually determined) "grassland" is studied. Highly detailed
meteorological tower data were combined with measured grassland impedances. These
data are fed to the full-wave one-directional Green's function parabolic equation
sound propagation model. The variation, even under these good-practice
measurement conditions, is found to be large, and strongly dependent on sound
frequency, source height, receiver height, and propagation distance. When
assessing the specific sound pressure level from a multitude of sources, this
variation strongly decreases compared to a low-height single source. Besides
absolute variations, fluctuations in the transmission loss between a close point
and a more distant one are discussed in this paper. The variation ranges give an
idea on this systematic uncertainty when performing short-term measurements, and
their impact on convergence to yearly averaged equivalent sound pressure levels.
PMID- 29960450
TI - Acoustic features of auditory medical alarms-An experimental study of alarm
volume.
AB - Audible alarms are a ubiquitous feature of all high-paced, high-risk domains such
as aviation and nuclear power where operators control complex systems. In such
settings, a missed alarm can have disastrous consequences. It is conventional
wisdom that for alarms to be heard, "louder is better," so that alarm levels in
operational environments routinely exceed ambient noise levels. Through a robust
experimental paradigm in an anechoic environment to study human response to
audible alerting stimuli in a cognitively demanding setting, akin to high-tempo
and high-risk domains, clinician participants responded to patient crises while
concurrently completing an auditory speech intelligibility and visual vigilance
distracting task as the level of alarms were varied as a signal-to-noise ratio
above and below hospital background noise. There was little difference in
performance on the primary task when the alarm sound was -11 dB below background
noise as compared with +4 dB above background noise-a typical real-world
situation. Concurrent presentation of the secondary auditory speech
intelligibility task significantly degraded performance. Operator performance can
be maintained with alarms that are softer than background noise. These findings
have widespread implications for the design and implementation of alarms across
all high-consequence settings.
PMID- 29960451
TI - Engineering Noise Control, Fifth Edition.
PMID- 29960452
TI - Surface curvature effects on the tonal noise of a wall-mounted finite airfoil.
AB - This paper is concerned with the influence of camber on the noise of a wall
mounted finite airfoil with natural boundary layer transition. Tonal noise
measurements taken in an aeroacoustic wind tunnel are presented for airfoils with
aspect ratio of 2, NACAxx12 profile and camber between 0 and 6% at 40% chord. The
results show camber is an important parameter that determines the operating
conditions for which acoustic tone generation occurs and the number and intensity
of the tones produced. Airfoils with 0%-2% camber have an acoustic signature that
is dominated by a high amplitude primary tone, whereas the spectra of airfoils
with higher camber of 4%-6% feature a more pronounced side tone structure. Tonal
noise production does not collapse with lift coefficient, demonstrating that the
local flow conditions influence the noise source. Tonal noise production is
explained in terms of changes to mean flow topology, namely the location of flow
separation, which is linked to tonal noise generation. Scaling of airfoil tonal
noise is found to vary with angle of attack and pressure gradient. Empirical
scaling laws for the primary tone frequency dependence on velocity are also
derived for the cambered airfoils.
PMID- 29960453
TI - Compressive acoustic holography with block-sparse regularization.
AB - Sparse reconstruction methods, such as Compressive Sensing, are powerful methods
in acoustic array processing, as they make wideband reconstruction possible.
However, when addressing sound fields that are not necessarily sparse (e.g., in
acoustic near-fields, reflective environments, extended sources, etc.), the
methods can lead to a poor reconstruction of the sound field. This study examines
the use of sparse analysis priors to promote block-sparse solutions. In
particular, a Fused Total Generalized Variation (F-TGV) method is developed, to
analyze the sound field in the near-field of acoustic sources. The method
promotes sparsity both on the spatial derivatives of the solution and on the
solution itself, thus seeking solutions where the non-zero coefficients are
grouped together. The performance of the method is examined numerically and
experimentally, and compared with established methods. The results indicate that
the F-TGV method is suitable to examine both compact and spatially extended
sources. The method is promising for its generality, robustness to noise, and the
capability to provide a wideband reconstruction of sound fields that are not
necessarily sparse.
PMID- 29960454
TI - Processor dependent bias of spatial spectral estimates from coprime sensor
arrays.
AB - Coprime sensor arrays (CSAs) can estimate the directions of arrival of O(MN)
narrowband plane wave sources using only O(M+N) sensors with the CSA product
processor. Processing data from a finite aperture array effectively smears the
true spatial power spectral density (PSD) with a kernel function determined by
both the array geometry and the processing of the signals observed by the array.
This paper examines the asymptotic behaviors of the kernel functions resulting
from two different processors applied to a CSA sampling geometry in the limit of
large aperture. The kernel functions of the product processed CSA and
conventionally beamformed coprime sensor arrays (CBF CSA) are compared to the
baseline of the kernel of a densely populated uniform line array (ULA) of similar
aperture. At the limit of large aperture, the product processed CSA estimate is
asymptotically unbiased like the ULA, while the CBF CSA estimate is not. The PSD
estimates computed from the CSA processors are compared when spatially correlated
Gaussian noise is an input to the array to highlight the bias issues.
PMID- 29960455
TI - Temporal factors in cochlea-scaled entropy and intensity-based intelligibility
predictions.
AB - Cochlea-scaled entropy (CSE) was proposed as a signal-based metric for automatic
detection of speech regions most important for intelligibility, but its proposed
superiority over traditional linguistic and psychoacoustical characterisations
was not subsequently confirmed. This paper shows that the CSE concept is closely
related to intensity and as such captures similar speech regions. However, a
slight but significant advantage of a CSE over an intensity-based
characterisation was observed, associated with a time difference between the two
metrics, suggesting that the CSE index may capture dynamical properties of the
speech signal crucial for intelligibility.
PMID- 29960456
TI - Time delay estimation based on log-sum and l-norm penalized minor component
analysis.
AB - Time-delay estimation (TDE), which measures the relative time delay between
different receivers, is a fundamental approach for identifying, localizing, and
tracking radiating sources. The generalized cross-correlation method is the most
popular and is well explained in a landmark paper by Knapp and Carter [(1976).
IEEE Trans. Acoust. Speech Signal Process. 24(4), 320-327]. Adaptive eigenvalue
decomposition- (EVD) based algorithms have also been developed to improve TDE
performance, especially in reverberant environments. This paper extends the
adaptive EVD algorithm to utilize the sparsity in transfer channel between source
and receivers. Two estimation algorithms based on the log-sum and lp-norm
penalized minor component analysis by excitatory and inhibitory learning rules is
proposed. In addition, simulations with uncorrelated, correlated noise and
reverberation for several signal-to-noise ratios are performed to show the
improved estimation performance in noise and reverberation.
PMID- 29960457
TI - Acoustic analysis of misarticulated trills in cleft lip and palate children.
AB - In this paper, acoustic analysis of misarticulated trills in cleft lip and palate
speakers is carried out using excitation source based features: strength of
excitation and fundamental frequency, derived from zero-frequency filtered
signal, and vocal tract system features: first formant frequency (F1) and trill
frequency, derived from the linear prediction analysis and autocorrelation
approach, respectively. These features are found to be statistically significant
while discriminating normal from misarticulated trills. Using acoustic features,
dynamic time warping based trill misarticulation detection system is
demonstrated. The performance of the proposed system in terms of the F1-score is
73.44%, whereas that for conventional Mel-frequency cepstral coefficients is
66.11%.
PMID- 29960458
TI - A sparsification and reconstruction strategy for compressed sensing photoacoustic
tomography.
AB - Compressed sensing (CS) is a promising approach to reduce the number of
measurements in photoacoustic tomography (PAT) while preserving high spatial
resolution. This allows to increase the measurement speed and reduce system
costs. Instead of collecting point-wise measurements, in CS one uses various
combinations of pressure values at different sensor locations. Sparsity is the
main condition allowing to recover the photoacoustic (PA) source from compressive
measurements. In this paper, a different concept enabling sparse recovery in CS
PAT is introduced. This approach is based on the fact that the second time
derivative applied to the measured pressure data corresponds to the application
of the Laplacian to the original PA source. As typical PA sources consist of
smooth parts and singularities along interfaces, the Laplacian of the source is
sparse (or at least compressible). To efficiently exploit the induced sparsity, a
reconstruction framework is developed to jointly recover the initial and modified
sparse sources. Reconstruction results with simulated as well as experimental
data are given.
PMID- 29960459
TI - Sound transmission loss through triple-walled cylindrical shells with porous
layers.
AB - Sound transmission loss through triple-walled sandwich cylindrical shells in the
presence of an external mean flow is analytically examined. Love's theory and a
simplified method based on Biot's theory are considered to describe the motions
of thin isotropic shells and wave propagation in the porous material cores,
respectively. The random incidence transmission loss in a diffuse field is
calculated numerically by considering the limiting incidence angle due to the
total internal reflection. The analytical model and numerical code are validated
against both experimental and analytical results reported by previous studies.
The transmission loss of triple-walled structure in the diffuse sound field is
compared with its double-walled counterpart at the same weight. The results
generally show a superior performance in the sound insulation for the triple
walled shell, considerably at mid-high and high frequencies, in comparison with
its double-walled counterpart at the same weight. The effects of sandwich shell
configuration and air gap depth are also investigated on the sound transmission
loss.
PMID- 29960460
TI - Sound source localization and speech enhancement with sparse Bayesian learning
beamforming.
AB - Speech localization and enhancement involves sound source mapping and
reconstruction from noisy recordings of speech mixtures with microphone arrays.
Conventional beamforming methods suffer from low resolution, especially with a
limited number of microphones. In practice, there are only a few sources compared
to the possible directions-of-arrival (DOA). Hence, DOA estimation is formulated
as a sparse signal reconstruction problem and solved with sparse Bayesian
learning (SBL). SBL uses a hierarchical two-level Bayesian inference to
reconstruct sparse estimates from a small set of observations. The first level
derives the posterior probability of the complex source amplitudes from the data
likelihood and the prior. The second level tunes the prior towards sparse
solutions with hyperparameters which maximize the evidence, i.e., the data
probability. The adaptive learning of the hyperparameters from the data auto
regularizes the inference problem towards sparse robust estimates. Simulations
and experimental data demonstrate that SBL beamforming provides high-resolution
DOA maps outperforming traditional methods especially for correlated or non
stationary signals. Specifically for speech signals, the high-resolution SBL
reconstruction offers not only speech enhancement but effectively speech
separation.
PMID- 29960461
TI - Multiscale prediction of acoustic properties for glass wools: Computational study
and experimental validation.
AB - This work is concerned with the multiscale prediction of the transport and sound
absorption properties associated with industrial glass wool samples. In the first
step, an experimental characterization is performed on various products using
optical granulometry and porosity measurements. A morphological analysis, based
on scanning electron imaging, is further conducted to identify the probability
density functions associated with the fiber angular orientation. The key
morphological characterization parameters of the microstructure, which serve as
input parameters of the model, include the porosity, the weighted volume diameter
accounting for both lengths and diameters of the analyzed fibers (and therefore
the specific surface area of the random fibrous material), and the preferred out
of-plane fiber orientation generated by the manufacturing process. A
computational framework is subsequently proposed and allows for the
reconstruction of an equivalent fibrous network. A fully stochastic
microstructural model, parameterized by the probability laws inferred from the
database, is also proposed herein. Multiscale simulations are carried out to
estimate transport properties and sound absorption. With no adjustable parameter,
the results accounting for ten different samples obtained with various processing
parameters are finally compared with the experimental data and used to assess the
relevance of the reconstruction procedures and the multiscale computations.
PMID- 29960462
TI - Bottlenose dolphin (Tursiops truncatus) discrimination of harmonic stimuli with
range-dependent signal degradation.
AB - The importance of perceived sound source distance has been noted in controlled
exposure studies with free-ranging marine mammals. Different behavioral reactions
have been observed for sonar exposures with a similar received level but
differing source distances. This psychophysical study examined bottlenose
dolphins' use of range-dependent acoustic features in classifying frequency
modulated tonal stimuli (~10-kHz fundamental). Repetitive tones with simulated
range-dependent high-frequency attenuation (HFA) and reverberation (REV) were
presented with roving levels (levels varied +/-10 dB). The dolphins were trained
to produce a phonic response upon hearing tones simulating relatively distant 30
km sources and to withhold response for closer-range tones. Once this behavior
was reliably performed, probe trials with intermediate ranges were used to
examine stimulus classification based on HFA and REV. Dolphins responded to
nearly all probe trials with ranges of 10 and 20 km, while responses were less
frequent at 1 and 2 km. Probes with HFA and REV decoupled from simulated source
distance indicated that the dolphins used HFA to a greater degree than REV in
response decisions. These results suggest that dolphins can classify harmonic
signals based on range-dependent HFA and REV independent of received level,
making these cues potentially useful in deciding behavioral reactions to acoustic
sources.
PMID- 29960463
TI - Baseline-free guided wave damage detection with surrogate data and dictionary
learning.
AB - In guided wave structural health monitoring, damage detection is often
accomplished by comparing measurements before damage (i.e., baseline data) and
after damage (i.e., test data). Yet, in practical scenarios, baseline data is
often unavailable. Data from surrogate structures (structures similar to the test
structure) could replace baseline data, but due to small differences in material
properties, such as thickness, temperature, and other effects, this data is often
unreliable. In this paper, a dictionary learning framework overcomes this
challenge and detects damage with surrogate information. The framework combines
wave propagation characteristics of a test structure with geometric information
from surrogate structures to create a synthetic damage-free baseline. The test
data is compared with the synthetic baseline to detect damage. The framework is
evaluated with four 108 mm *108 mm plates: two 1.6-mm thick aluminum plates, one
1.6-mm thick steel plate, and one 6.25 mm thick aluminum plate. The framework is
applied to each test structure after learning from plates with different material
properties and thicknesses. With full wavefield data, this paper successfully
isolates reflections from a mass without using explicit baseline data.
Furthermore, with sparse guided wave data, this paper shows that a drop in a
correlation coefficient can detect a mass without using explicit baseline data.
PMID- 29960464
TI - Separability of wave solutions in nonlinear brass instrument modelling.
AB - Travelling wave representations of wave propagation are commonly employed in
brass instrument modeling and have been extended to the nonlinear regimes. For
the case of a real brass instrument, the assumptions that lead to the travelling
wave solutions no longer strictly hold. The validity of these assumptions is
investigated here with regard to two typical parts of brass instrument geometry.
The first example shows that there is a small interaction between forwards and
backwards travelling waves in a cylindrical tube. The second example highlights
nonlinear backscattering of a traveling wave caused by variations in the tube
cross-sectional area.
PMID- 29960465
TI - Sparse broadband time varying acoustic response modeling and estimation from an
undersampled vertical array with application to underwater communications.
AB - Sparse broadband time varying acoustic response functions associated with
horizontally stratified environments can be well estimated from an undersampled
vertical array. The sparsity of the arrivals here is captured by means of a two
component Gaussian mixture model. The implied posterior expectation of the
bifrequency function serves to attenuate low amplitude non-coherent arrivals
while leaving coherent arrivals at the array unchanged. This estimate of the
acoustic response specifies a time varying increment operator that unravels the
time varying motion between the source and receiver array allowing for a further
sparsification of the response. This additional improved sparsity allows for
improved coherent multipath combining at the receiver. The model is applied to a
three element vertical array during a set of broadband acoustic observations in
the shallow waters of Buzzard's Bay, MA. M-ary orthogonal spread spectrum
acoustic transmissions at 32.5 kHz center frequency and 25 kHz bandwidth are
considered. With M = 4, throughput rates of 95 bps are tested. At 2 km and at a
receive signal-to-noise ratio per element of -15.5 dB, a 3 element undersampled
vertical array achieved bit error rates less than 10-5.
PMID- 29960466
TI - Empirical Bayes based relative impulse response estimation.
AB - Relative impulse responses (ReIRs) have several applications in speech
enhancement, noise suppression and source localization for multi-channel speech
processing in reverberant environments. Estimating the ReIRs can be reduced to a
system identification problem. A system identification method using an empirical
Bayes framework is proposed and its application for spatial source subtraction in
audio signal processing is evaluated. The proposed estimator allows for
incorporating prior structure information of the system into the estimation
procedure, leading to an improved performance especially in the presence of
noise. The estimator utilizes the sparse Bayesian learning algorithm with
appropriate priors to characterize both the early reflections and reverberant
tails. The mean squared error of the proposed estimator is studied and an
extensive experimental study with real-world recordings is conducted to show the
efficacy of the proposed approach over other competing approaches.
PMID- 29960467
TI - Mechanisms of active control of sound radiation from an opening with boundary
installed secondary sources.
AB - Previous work has demonstrated that installing secondary sources at the edge of a
cavity opening can reduce sound radiation through it, but the mechanisms are not
clear, which is investigated in this paper by using the modal decomposition
method. It is found that a double layer edge system achieves better performance
than a single layer system because secondary sources at the edge of the same
layer cannot excite some modes effectively and those at different heights
compensate this. There exists an upper limit frequency for the systems with
boundary installed secondary sources, which is mainly decided by the length of
the short side of the opening. More secondary source layers at the edge will
increase the upper limit frequency.
PMID- 29960468
TI - Binaural rendering of Ambisonic signals by head-related impulse response time
alignment and a diffuseness constraint.
AB - Binaural rendering of Ambisonic signals is of great interest in the fields of
virtual reality, immersive media, and virtual acoustics. Typically, the spatial
order of head-related impulse responses (HRIRs) is considerably higher than the
order of the Ambisonic signals. The resulting order reduction of the HRIRs has a
detrimental effect on the binaurally rendered signals, and perceptual evaluations
indicate limited externalization, localization accuracy, and altered timbre. In
this contribution, a binaural renderer, which is computed using a frequency
dependent time alignment of HRIRs followed by a minimization of the squared error
subject to a diffuse-field covariance matrix constraint, is presented. The
frequency-dependent time alignment retains the interaural time difference (at low
frequencies) and results in a HRIR set with lower spatial complexity, while the
constrained optimization controls the diffuse-field behavior. Technical
evaluations in terms of sound coloration, interaural level differences, diffuse
field response, and interaural coherence, as well as findings from formal
listening experiments show a significant improvement of the proposed method
compared to state-of-the-art methods.
PMID- 29960469
TI - Local compressed convex spectral embedding for bird species identification.
AB - This paper proposes a multi-layer alternating sparse-dense framework for bird
species identification. The framework takes audio recordings of bird
vocalizations and produces compressed convex spectral embeddings (CCSE). Temporal
and frequency modulations in bird vocalizations are ensnared by concatenating
frames of the spectrogram, resulting in a high dimensional and highly sparse
super-frame-based representation. Random projections are then used to compress
these super-frames. Class-specific archetypal analysis is employed on the
compressed super-frames for acoustic modeling, obtaining the convex-sparse CCSE
representation. This representation efficiently captures species-specific
discriminative information. However, many bird species exhibit high intra-species
variations in their vocalizations, making it hard to appropriately model the
whole repertoire of vocalizations using only one dictionary of archetypes. To
overcome this, each class is clustered using Gaussian mixture models (GMM), and
for each cluster, one dictionary of archetypes is learned. To calculate CCSE for
any compressed super-frame, one dictionary from each class is chosen using the
responsibilities of individual GMM components. The CCSE obtained using this GMM
archetypal analysis framework is referred to as local CCSE. Experimental results
corroborate that local CCSE either outperforms or exhibits comparable
performances to existing methods including support vector machine powered by
dynamic kernels and deep neural networks.
PMID- 29960470
TI - Comparison between adaptive and adjustment procedures for binaural loudness
balancing.
AB - Binaural loudness balancing is performed in research and clinical practice when
fitting bilateral hearing devices, and is particularly important for bimodal
listeners, who have a bilateral combination of a hearing aid and a cochlear
implant. In this study, two psychophysical binaural loudness balancing procedures
were compared. Two experiments were carried out. In the first experiment, the
effect of procedure (adaptive or adjustment) on the balanced loudness levels was
investigated using noise band stimuli, of which some had a frequency shift to
simulate bimodal hearing. In the second experiment, the adjustment procedure was
extended. The effect of the starting level of the adjustment procedure was
investigated and the two procedures were again compared for different reference
levels and carrier frequencies. Fourteen normal hearing volunteers participated
in the first experiment, and 38 in the second experiment. Although the final
averaged loudness balanced levels of both procedures were similar, the adjustment
procedure yielded smaller standard deviations across four test sessions. The
results of experiment 2 demonstrated that in order to avoid bias, the adjustment
procedure should be conducted twice, once starting from below and once from above
the expected balanced loudness level.
PMID- 29960471
TI - When singing with cochlear implants, are two ears worse than one for
perilingually/postlingually deaf individuals?
AB - Many individuals with bilateral cochlear implants hear different pitches when
listening with their left versus their right cochlear implant. This conflicting
information could potentially increase the difficulty of singing with cochlear
implants. To determine if bilateral cochlear implants are detrimental for singing
abilities, ten perilingually/postlingually deaf bilateral adult cochlear implant
users were asked to sing "Happy Birthday" when using their left, right, both, or
neither cochlear implant. The results indicated that bilateral cochlear implant
users have more difficulty singing the appropriate pitch contour when using both
cochlear implants as opposed to the better ear alone.
PMID- 29960472
TI - A model-based Bayesian framework for sound source enumeration and direction of
arrival estimation using a coprime microphone array.
AB - Coprime microphone arrays use sparse sensing to achieve greater degrees of
freedom, while the coprimality of the microphone subarrays help resolve grating
lobe ambiguities. The result is a narrow beam at frequencies higher than the
spatial Nyquist limit allows, with residual side lobes arising from aliasing.
These side lobes can be mitigated when observing broadband sources, as shown by
Bush and Xiang [J. Acoust. Soc. Am. 138, 447-456 (2015)]. Peak positions may
indicate directions of arrival in this case; however, one must first ask how many
sources are present. In answering this question, this work employs a model
describing scenes with potentially multiple concurrent sound sources. Bayesian
inference is used to first select which model the data prefer from competing
models before estimating model parameters, including the particular source
locations. The model is a linear combination of Laplace distribution functions
(one per sound source). The likelihood function is explored by a Markov Chain
Monte Carlo method called nested sampling in order to evaluate Bayesian evidence
for each model. These values increase monotonically with model complexity;
however, diminished returns are penalized via an implementation of Occam's razor.
PMID- 29960473
TI - A theoretical model of fuselage pressure levels due to fan tones radiated from
the intake of an installed turbofan aero-engine.
AB - An existing theoretical model to predict the pressure levels on an aircraft's
fuselage is improved by incorporating a more physically realistic method to
predict fan tone radiation from the intake of an installed turbofan aero-engine.
Such a model can be used as part of a method to assess cabin noise. Fan tone
radiation from a turbofan intake is modelled using the exact solution for the
radiated pressure from a spinning mode exiting a semi-infinite cylindrical duct
immersed in a uniform flow. This approach for a spinning duct mode incorporates
scattering/diffraction by the intake lip, enabling predictions of the radiated
pressure valid in both the forward and aft directions. The aircraft's fuselage is
represented by an infinitely long, rigid cylinder. There is uniform flow aligned
with the cylinder, except close to the cylinder's surface where there is a
constant-thickness boundary layer. In addition to single mode calculations it is
shown how the model may be used to rapidly calculate a multi-mode incoherent
radiation from the engine intake. Illustrative results are presented which
demonstrate the relative importance of boundary-layer shielding both upstream and
downstream of the source, as well as examples of the fuselage pressure levels due
to a multi-mode tonal source at high Helmholtz number.
PMID- 29960474
TI - Distributed compressed sensing based channel estimation for underwater acoustic
multiband transmissions.
AB - Distributed compressed sensing techniques are applied to enhance sparse channel
estimation performance in underwater acoustic multiband systems. The core idea is
to use receptions from multiple sub-bands to enhance the detection of channel tap
positions. A known variant of the orthogonal matching pursuit (OMP) algorithm
based on the distributed compressed sensing principle is simultaneous orthogonal
matching pursuit (SOMP). However, the impulse responses across multiple sub-bands
may have different arrival structures, although they often show a certain level
of similarity. To address such differences at the sub-bands, a multiple selection
strategy is applied to select multiple candidates at individual sub-bands at each
iteration. This is different from the conventional OMP and SOMP algorithms that
select only one candidate at each iteration. When the multiple selection strategy
is combined with the SOMP algorithm, the proposed algorithm is referred to as JB
MSSOMP algorithm. To take advantage of channel coherence between adjacent data
blocks from different sub-bands, the multiple selection strategy is further used
over time. This leads to JBT-MSSOMP algorithm. Computer simulations show improved
channel estimation performance of the proposed JB-MSSOMP and JBT-MSSOMP
algorithms over the OMP or SOMP algorithms. Communication data from a recent
acoustic experiment demonstrates improved receiver performance with the proposed
channel estimators.
PMID- 29960475
TI - Introduction to special issue on compressive sensing in acoustics.
AB - Compressive sensing (CS) in acoustics has received significant attention in the
last decade, and thus motivates this special issue. CS emerged from the signal
processing and applied math community and has since generated compelling results
in acoustics. This special issue primarily addresses the acoustics CS topics of
compressive beamforming and holography. For a sound field observed on a sensor
array, CS reconstructs the direction of arrival of multiple sources using a
sparsity constraint. Similarly, in holography a sparsity constraint gives
improved sound field reconstruction over conventional l2-regularization. Other
topics in this issue include sparse array configurations (as co-arrays) and
sparse sensing in acoustic communication.
PMID- 29960476
TI - Stochastic matched-field localization of an acoustic source based on principles
of Riemannian geometry.
AB - Passive localization of acoustic sources is treated within a geometric framework
where non-Euclidean distance measures are computed between a cross-spectral
density estimate of received data on a vertical array and a set of stochastic
replica steering matrices, rather than traditional replica steering vectors. A
processing scheme involving matrix-matrix comparisons where steering matrices, as
functions of the replica source coordinates, naturally incorporate environmental
variability or uncertainty provides a general framework for considering the
acoustic inverse source problem in an ocean waveguide. Within this context a
subset of matched-field processors is examined, based on recent advances in the
application of non-Euclidean geometry to statistical classification of data
feature clusters. The matrices are interpreted abstractly as points in a
Riemannian manifold, and an appropriately defined distance measure between pairs
of matrices on this manifold defines a matched-field processor for estimating
source location. Acoustic simulations are performed for a waveguide comprising
both a depth-dependent sound-speed profile perturbed by linear internal gravity
waves and a depth-correlated surface noise field, providing an example of the
viability of this approach to passive source localization in the presence of
sound-speed variability.
PMID- 29960478
TI - A performance metric for screen selection with the acoustic single pixel imager.
AB - In the recent literature, an Acoustic Single-Pixel Imager has been successfully
developed for source localization in a two-dimensional waveguide. Source bearing
angle estimation was carried out by applying sparse recovery techniques on sensor
measurements taken over different imaging screens. This paper shows that the
Mutual Coherence of the sensing matrix can be used as a metric to predict the
source localization capability of the single-pixel imaging system. In particular,
this paper's analysis focuses on the sparsity of open cells within the imaging
screen and the number of imaging screens used to maximize the probability of
correct detection over varying levels of source sparsity. In this work, a
simulation environment to demonstrate how the mutual coherence of the sensing
matrix correlates with source localization performance over source sparsity,
sparsity of open screen cells, and number of measurements used for sparse
recovery is developed. The analysis shows that the leading factor in source
localization performance gains is primarily from the number of imaging screens
used to measure the acoustic wave-field.
PMID- 29960477
TI - Human ossicular-joint flexibility transforms the peak amplitude and width of
impulsive acoustic stimuli.
AB - The role of the ossicular joints in the mammalian middle ear is still debated.
This work tests the hypothesis that the two synovial joints filter potentially
damaging impulsive stimuli by transforming both the peak amplitude and width of
these impulses before they reach the cochlea. The three-dimensional (3D) velocity
along the ossicular chain in unaltered cadaveric human temporal bones (N = 9),
stimulated with acoustic impulses, is measured in the time domain using a Polytec
(Waldbronn, Germany) CLV-3D laser Doppler vibrometer. The measurements are
repeated after fusing one or both of the ossicular joints with dental cement.
Sound transmission is characterized by measuring the amplitude, width, and delay
of the impulsive velocity profile as it travels from the eardrum to the cochlea.
On average, fusing both ossicular joints causes the stapes velocity amplitude and
width to change by a factor of 1.77 (p = 0.0057) and 0.78 (p = 0.011),
respectively. Fusing just the incudomalleolar joint has a larger effect on
amplitude (a factor of 2.37), while fusing just the incudostapedial joint
decreases the stapes velocity on average. The 3D motion of the ossicles is
altered by fusing the joints. Finally, the ability of current computational
models to predict this behavior is also evaluated.
PMID- 29960479
TI - Envelope following responses, noise exposure, and evidence of cochlear
synaptopathy in humans: Correction and comment.
AB - A correction and comment are provided for a recent article by Paul, Waheed,
Bruce, and Roberts [(2017). J. Acoust. Soc. Am. 142(5), EL434-EL440].
PMID- 29960480
TI - Translations of spherical harmonics expansion coefficients for a sound field
using plane wave expansions.
AB - A translation method for the spherical harmonics expansion coefficients of a
sound field using plane wave expansions is proposed. It is based on the
decomposition of a plane wave in the spherical harmonics domain and without the
use of the spherical harmonics addition theorem, thus is very computationally
efficient. Simulations are conducted for validation. The stabilities of the
translations are compared with the conventional method in terms of matrix
condition numbers. The proposed method is demonstrated to be more robust as the
frequency increases and when upscaling the coefficients. Besides, the computation
is much faster when high truncated orders are solved.
PMID- 29960481
TI - Slitted leading edge profiles for the reduction of turbulence-aerofoil
interaction noise.
AB - Aerofoils operating in a turbulent flow are an efficient source of noise
radiation by scattering vorticity into sound at the leading edge (LE). Much work
has now been undertaken demonstrating the effectiveness of serrations, or
undulations, introduced onto the LE can substantially reduce broadband LE
interaction noise. However, all of this work is focused on sinusoidal LE
serration profiles. In this paper, an alternative profile is proposed that is
capable of providing significantly greater noise reductions than the maximum
noise reductions that can be achieved by single-wavelength serrations of the same
peak-to-root amplitude. In its most general realization, the LE serration
profiles simply comprise of a sawtooth or single wavelength serration for which
every root has a single narrow slit. This simple geometry, upon interaction with
a turbulent flow, produces compact source regions at either end of the slit,
which then destructively interfere, leading to considerably less efficient noise
radiation than conventional single-wavelength geometries. The paper will
demonstrate experimentally that even slits by themselves can provide greater
levels of noise reduction than conventional profiles of the same peak-to-root
amplitude.
PMID- 29960482
TI - Sparse regularization for reconstructing transient sources with time domain
nearfield acoustical holography.
AB - In this paper, the l1-norm sparse regularization method is applied to the time
domain reconstruction of transient acoustic fields such as impulse noise. This
method properly reconstructs the back-propagated sound field where its amplitude
should be null: for transient sources, this occurs mostly for positions and times
that precede the arrival of the first wave front. Therefore, it significantly
reduces causal errors typically found in time domain reconstruction when standard
Tikhonov regularizations is applied. The reconstructions obtained from both
Tikhonov and sparse regularization methods are compared using a transient baffled
piston model, and show that the global root-mean-square (RMS) error is
significantly reduced when using sparse regularization. The improvement provided
depends on the level of sparsity of the reconstructed signal. For the studied
cases, it can represent a reduction of the global RMS error by up to a factor of
3. The performance of Pareto frontier curve for predicting the optimal sparse
regularization parameter is examined; it leads to accurate predictions especially
for lower noise levels. Finally, sparse regularization is applied to experimental
data over time and spatial domains in order to obtain an accurate reconstruction
of the transient sound field produced by an impacted plate.
PMID- 29960483
TI - Broadband characterization of plastic and high intensity therapeutic ultrasound
phantoms using time delay spectrometry-With validation using Kramers-Kronig
relations.
AB - Time delay spectrometry (TDS) is extended for broadband characterization of
plastics (low-density polyethylene, LDPE) and tissue-mimicking material (TMM).
The results suggest that TDS and the conventional broadband pulse method give
comparable measurements for frequency-dependent attenuation coefficient and phase
velocity near the center frequency, where signal-to-noise ratio is high. However,
TDS measurements show enhanced bandwidth for attenuation coefficient of 30%-40%
(LDPE) and 89%-100% (TMM) and for phase velocity of 43% (LDPE) and 36% (TMM) for
a single transmitter/receiver pair. In addition, TDS provides measurements of
dispersion that are consistent with predictions based on the Kramers-Kronig
relations to within 5 m/s over the band from 2 to 12 MHz in LDPE and to within 1
m/s in TMM over the band from 0.5 to 29 MHz.
PMID- 29960484
TI - Exploiting time varying sparsity for underwater acoustic communication via
dynamic compressed sensing.
AB - While it has been recognized that the multipath structure of the underwater
acoustic (UWA) channel offers the potential for compressed sensing (CS) sparsity
exploitation, the rapidly time varying arrivals induced by highly dynamic
surfaces unfortunately pose significant difficulties to channel estimation. From
the viewpoint of underwater acoustic propagation, with the exception of the
highly time varying arrivals caused by dynamic surface, generally there exist
relatively stationary or slowly changing arrivals caused by direct path or bottom
reflection, which imply the adoption of a discriminate estimation method to
handle sparse components with different time variation scale. By modeling the
time varying UWA channels as a sparse set consisting of constant and time-varying
supports, in this paper, estimation of time varying UWA channel is transformed
into a problem of dynamic compressed sensing sparse recovery. The combination of
a Kalman filter and compressed sensing is adopted to pursue the solution of it.
Numerical simulations demonstrate the superiority of the proposed algorithm. In
the form of a channel-estimation-based decision-feedback equalizer, the
experimental results with the field data obtained in a shallow water acoustic
communication experiment indicate that the proposed dynamic compressed sensing
algorithm outperforms classic algorithms as well as CS algorithms.
PMID- 29960485
TI - Deep learning models to remix music for cochlear implant users.
AB - The severe hearing loss problems that some people suffer can be treated by
providing them with a surgically implanted electrical device called cochlear
implant (CI). CI users struggle to perceive complex audio signals such as music;
however, previous studies show that CI recipients find music more enjoyable when
the vocals are enhanced with respect to the background music. In this manuscript
source separation (SS) algorithms are used to remix pop songs by applying gain to
the lead singing voice. This work uses deep convolutional auto-encoders, a deep
recurrent neural network, a multilayer perceptron (MLP), and non-negative matrix
factorization to be evaluated objectively and subjectively through two different
perceptual experiments which involve normal hearing subjects and CI recipients.
The evaluation assesses the relevance of the artifacts introduced by the SS
algorithms considering their computation time, as this study aims at proposing
one of the algorithms for real-time implementation. Results show that the MLP
performs in a robust way throughout the tested data while providing levels of
distortions and artifacts which are not perceived by CI users. Thus, an MLP is
proposed to be implemented for real-time monaural audio SS to remix music for CI
users.
PMID- 29960486
TI - Thermal analysis of ultrasound-powered miniaturized implants: A tissue-phantom
study.
AB - Neurological implants that harvest ultrasound power have the potential to provide
long-term stimulation without complications associated with battery power. An
important safety question associated with long-term operation of the implant
involves the heat generated by the interaction of the device with the ultrasound
field. A study was performed in which the temperature rise generated by this
interaction was measured. Informed by temperature data from thermocouples outside
the ultrasound beam, a mathematical inverse method was used to determine the
volume heat source generated by ultrasound absorption within the implant as well
as the surface heat source generated within the viscous boundary layer on the
surface of the implant. For the test implant used, it was determined that most of
the heat was generated in the boundary layer, giving a maximum temperature rise
~5 times that for absorption in an equivalent volume of soft tissue. This result
illustrates that thermal safety guidelines based solely on ultrasound absorption
of tissue alone are not sufficient. The method presented represents an
alternative approach for quantifying ultrasound thermal effects in the presence
of implants. The analysis shows a steady temperature rise of about 0.2 degrees C
for every 100 mW/cm2 for the presented test implant.
PMID- 29960487
TI - Primary calibration by reciprocity method of high-frequency acoustic-emission
piezoelectric transducers.
AB - Although acoustic-emission (AE) piezoelectric transducers have distinctive
variations in sensitivity, depending on frequency, propagation medium, and
coupling, the vast majority of AE research is conducted by utilizing uncalibrated
AE transducers. As a consequence, most results obtained by different groups are
not comparable among each other. In this work, primary calibration by the method
of reciprocity is shown. Rayleigh and longitudinal wave calibration curves are
presented for piezoelectric high-frequency broadband transducer, mounted on steel
and aluminium, in the frequency range 300 kHz-4 MHz. Influences on primary
calibration of AE transducers, namely, by coupling medium, contact pressure, and
propagation medium, are investigated.
PMID- 29960488
TI - Application of a forward model of axisymmetric shear wave propagation in
viscoelastic media to shear wave elastography.
AB - A simple but general solution of Navier's equation for axisymmetric shear wave
propagation in a homogeneous isotropic viscoelastic medium is presented. It is
well-suited for use as a forward model for some acoustic radiation force impulse
based shear wave elastography applications because it does not require precise
knowledge of the strength of the source, nor its spatial or temporal
distribution. Instead, it depends on two assumptions: (1) the source distribution
is axisymmetric and confined to a small region near the axis of symmetry, and (2)
the propagation medium is isotropic and homogeneous. The model accounts for the
vector polarization of shear waves and exactly represents geometric spreading of
the shear wavefield, whether spherical, cylindrical, or neither. It makes no
assumption about the frequency dependence of material parameters, i.e., it is
material-model independent. Validation using measured shear wavefields excited by
acoustic radiation force in a homogeneous gelatin sample show that the model
accounts for well over 90% of the measured wavefield "energy." An optimal fit of
the model to simulated shear wavefields with noise in a homogeneous viscoelastic
medium enables estimation of both the shear storage modulus and shear wave
attenuation to within 1%.
PMID- 29960489
TI - Modeling underwater noise propagation from marine hydrokinetic power devices
through a time-domain, velocity-pressure solution.
AB - Marine hydrokinetic (MHK) devices generate electricity from the motion of tidal
and ocean currents, as well as ocean waves, to provide an additional source of
renewable energy available to the United States. These devices are a source of
anthropogenic noise in the marine ecosystem and must meet regulatory guidelines
that mandate a maximum amount of noise that may be generated. In the absence of
measured levels from in situ deployments, a model for predicting the propagation
of sound from an array of MHK sources in a real environment is essential. A set
of coupled, linearized velocity-pressure equations in the time-domain are derived
and presented in this paper, which are an alternative solution to the Helmholtz
and wave equation methods traditionally employed. Discretizing these equations on
a three-dimensional (3D), finite-difference grid ultimately permits a finite
number of complex sources and spatially varying sound speeds, bathymetry, and bed
composition. The solution to this system of equations has been parallelized in an
acoustic-wave propagation package developed at Sandia National Labs, called
Paracousti. This work presents the broadband sound pressure levels from a single
source in two-dimensional (2D) ideal and Pekeris wave-guides and in a 3D domain
with a sloping boundary. The paper concludes with demonstration of Paracousti for
an array of MHK sources in a simple wave-guide.
PMID- 29960490
TI - Effect of frequency mismatch and band partitioning on vocal tract length
perception in vocoder simulations of cochlear implant processing.
AB - The vocal tract length (VTL) of a speaker is an important voice cue that aids
speech intelligibility in multi-talker situations. However, cochlear implant (CI)
users demonstrate poor VTL sensitivity. This may be partially caused by the
mismatch between frequencies received by the implant and those corresponding to
places of stimulation along the cochlea. This mismatch can distort formant
spacing, where VTL cues are encoded. In this study, the effects of frequency
mismatch and band partitioning on VTL sensitivity were investigated in normal
hearing listeners with vocoder simulations of CI processing. The hypotheses were
that VTL sensitivity may be reduced by increased frequency mismatch and
insufficient spectral resolution in how the frequency range is partitioned,
specifically where formants lie. Moreover, optimal band partitioning might
mitigate the detrimental effects of frequency mismatch on VTL sensitivity.
Results showed that VTL sensitivity decreased with increased frequency mismatch
and reduced spectral resolution near the low frequencies of the band partitioning
map. Band partitioning was independent of mismatch, indicating that if a given
partitioning is suboptimal, a better partitioning might improve VTL sensitivity
despite the degree of mismatch. These findings suggest that customizing the
frequency partitioning map may enhance VTL perception in individual CI users.
PMID- 29960491
TI - A binaural auditory steering strategy based hearing-aid algorithm design.
AB - Beamforming techniques are widely used in hearing aids to enhance the
intelligibility of speech from a target direction, but they tend to isolate the
listener from their acoustic environment and distort spatial cues. The main
reason for this is that a typical beamformer method alters the head-related
transfer function of the individual users' ears and functions under monaural
assumptions instead of a binaural model. In this letter, a binaural auditory
steering strategy (BASS) is proposed for the design of asymmetrically presented
spatial filters which improves awareness of the surrounding acoustic environment
while preserving intelligibility from a target direction. Additionally, an
objective metric and the results of a subjective study to evaluate the
effectiveness of the BASS are presented.
PMID- 29960492
TI - Exploiting platform motion for passive source localization with a co-prime
sampled large aperture array.
AB - Co-prime array geometries have received a great deal of attention due to their
ability to discriminate O(MN) sources with only O(M + N) sensors. This has been
demonstrated both theoretically and in simulation. However, there are many
practical limitations that make it difficult to realize the enhanced degrees of
freedom when applying co-prime geometries to real acoustic data taken on a
horizontal line array. For instance, co-prime sampling leads to grating lobes
that can obscure lower signal-to-noise-ratio acoustic signals making them
difficult to detect. In this work, a synthetic aperture (SA) method is presented
for filling in holes and increasing redundancy in the difference co-array by
exploiting array motion. The SA method is applied to acoustic data collected off
the Southeastern shore of Florida on a fixed large aperture horizontal array.
Array motion is simulated by taking a co-prime sampled subarray and virtually
moving it along the horizontal aperture of the fixed array. It is demonstrated
that SA processing on real acoustic data results in reduced side-lobe and grating
lobe levels compared to that of the physical co-prime aperture.
PMID- 29960493
TI - Suppression of vocal responses to auditory perturbation with real-time visual
feedback.
AB - Speakers can adjust pitch using auditory feedback through a short-latency
corrective response known as the pitch-shift response (PSR). Suppression of the
PSR denotes on-line stabilization of pitch. In this paper, the hypothesis that
pitch-shift responses can be suppressed with real-time visual feedback of vocal
F0 is investigated. Mandarin speakers and naive speakers without tonal language
experience were instructed to produce the sustained vowel /a/ and Mandarin tone
/ma1/ in an audio-only condition and a separate audio-visual condition. Both
Mandarin speakers and naive speakers suppressed pitch-shift responses in the
audio-visual condition, regardless of task (/a/ or /ma1/) and stimulus magnitude
(25 cents or 200 cents). These findings suggest that multisensory feedback (audio
visual) can improve the stability of voice F0. The benefit of audio-visual
integration is independent of language experience.
PMID- 29960494
TI - Iterative algorithm for solving acoustic source characterization problems under
block sparsity constraints.
AB - In this paper, an iterative Compressive Sensing (CS) algorithm is proposed for
acoustical source characterization problems with block sparsity constraints.
Source localization and signal separation are accomplished in a unified CS
framework. The inverse problem is formulated with the Equivalent Source Method as
a linear underdetermined system of equations. As conventional approaches based on
convex optimization can be computationally expensive and fail to deal with
continuously distributed sources, the proposed approach that is adapted from the
Newton's method and is augmented with a special pruning procedure is capable of
solving the inverse problem far more efficiently with comparable accuracy. The
pruning procedure employs a binary mask that admits sparsity constraints of two
dimensional block sources. The binary mask is heuristic in that it tends to
promote nonzero positive source magnitudes. In each iteration, the source
amplitude vector is on one hand updated by the Newton's method and on the other
hand pruned with the binary mask. With the pruning procedure, the source
magnitudes become increasingly sparse and clustered such that the block
characteristics are enhanced. In the post-processing phase, particle velocity is
calculated on the basis of the equivalent source amplitudes. Numerical and
experimental investigations are conducted to validate the proposed technique. The
results have demonstrated the efficacy of the proposed Compressive Newton's
method in imaging block sources and extracting signal waveforms with little
computational cost, as compared to a convex optimization package.
PMID- 29960495
TI - A comparison of iterative sparse equivalent source methods for near-field
acoustical holography.
AB - During the past decade, several publications have described the use of
compressive sensing principles to extend the frequency range supported by a given
irregular microphone array for near-field acoustic holography. The applied
numerical source model has typically been of the type used for the equivalent
source method, i.e., a mesh of point sources, and a one-norm regularized inverse
problem has been solved using a very stable, but slow interior-point optimization
algorithm. A few publications have investigated the use of simpler and faster
iterative algorithms. The present paper gives a brief description of five such
iterative algorithms, and it compares their performances with that of the
interior-point algorithm based on a set of simulated measurements. A particular
focus is on the suitability for industrial applications. Finally, an optimal
choice of methodology is discussed based on the presented limited set of
simulated tests.
PMID- 29960496
TI - Wideband sparse spatial spectrum estimation using matrix filter with nulling in a
strong interference environment.
AB - Wideband direction of arrival (DOA) estimation using a sensor array plays a
fundamental role in passive sonar signal processing. Although sparsity-based DOA
estimation methods can attain high resolution in the condition of few snapshots
and low signal-to-noise ratio, the localization accuracy is seriously affected by
strong interferences. In this paper, a matrix filter with nulling (MFN) is used
to pass weak targets in sector-of-interest (passband) while attenuating the out
of-sector (stopband) interferences by forming deep nulls toward the directions of
interferences adaptively. Then, a method based on sparse spectrum fitting (SpSF)
and MFN is proposed to localize closely spaced wideband signals in a strong
interference environment. In comparison with the minimum variance distortionless
response and SpSF, the proposed method achieves higher localization accuracy,
which is verified by simulation and experimental results.
PMID- 29960497
TI - A corpus of audio-visual Lombard speech with frontal and profile views.
AB - This paper presents a bi-view (front and side) audiovisual Lombard speech corpus,
which is freely available for download. It contains 5400 utterances (2700 Lombard
and 2700 plain reference utterances), produced by 54 talkers, with each utterance
in the dataset following the same sentence format as the audiovisual "Grid"
corpus [Cooke, Barker, Cunningham, and Shao (2006). J. Acoust. Soc. Am. 120(5),
2421-2424]. Analysis of this dataset confirms previous research, showing
prominent acoustic, phonetic, and articulatory speech modifications in Lombard
speech. In addition, gender differences are observed in the size of Lombard
effect. Specifically, female talkers exhibit a greater increase in estimated
vowel duration and a greater reduction in F2 frequency.
PMID- 29960498
TI - Sparse sound field decomposition for super-resolution in recording and
reproduction.
AB - A sound field recording and reproduction method based on sparse sound field
decomposition is proposed. Most current methods are based on plane-wave or
harmonic decomposition of the pressure distribution obtained by microphones,
which leads to spatial aliasing artifacts with severe effects. This paper
proposes a method for sound field decomposition based on a generative model of
the sound field consisting of near-field source components and far-field plane
wave components. Since the distribution of the near-field source components can
be assumed to be spatially sparse, the pressure distribution obtained by the
microphones can be decomposed into these two components using sparse
decomposition algorithms. Using the proposed method, the sound field can be more
accurately interpolated and super-resolution in recording and reproduction can be
achieved. Experimental results show that the reproduction accuracy above the
spatial Nyquist frequency determined by the microphone intervals was improved
compared with that of the current methods.
PMID- 29960499
TI - Temporally weighting a time varying noise field to improve Green function
retrieval.
AB - The authors consider the retrieval of Green functions G from the correlations of
non-stationary non-fully diffuse noise incident on an array of sensors. Multiple
schemes are proposed for optimizing the time-varying weights with which
correlations may be stacked. Using noise records created by direct numerical
simulation of waves in a two-dimensional multiply scattering medium, cases are
shown in which conventional stacking does a poor job and for which the proposed
schemes substantially improve the recovered G, rendering it more causal and/or
more symmetric, and more similar to the actual G. It is found that the schemes
choose weights such that the effective incident intensity distribution is closer
to isotropic.
PMID- 29960500
TI - Effects of spectral resolution on spectral contrast effects in cochlear-implant
users.
AB - The identity of a speech sound can be affected by the long-term spectrum of a
preceding stimulus. Poor spectral resolution of cochlear implants (CIs) may
affect such context effects. Here, spectral contrast effects on a phoneme
category boundary were investigated in CI users and normal-hearing (NH)
listeners. Surprisingly, larger contrast effects were observed in CI users than
in NH listeners, even when spectral resolution in NH listeners was limited via
vocoder processing. The results may reflect a different weighting of spectral
cues by CI users, based on poorer spectral resolution, which in turn may enhance
some spectral contrast effects.
PMID- 29960501
TI - Reconstruction of the sound field in a room using compressive sensing.
AB - Capturing the impulse or frequency response functions within extended regions of
a room requires an unfeasible number of measurements. In this study, a method to
reconstruct the response at arbitrary points based on compressive sensing (CS) is
examined. The sound field is expanded into plane waves and their amplitudes are
estimated via CS, obtaining a spatially sparse representation of the sound field.
The validity of the CS assumptions are discussed, namely, the assumption of the
wave field spatial sparsity (which depends strongly on the properties of the
specific room), and the coherence of the sensing matrix due to different spatial
sampling schemes. An experimental study is presented in order to analyze the
accuracy of the reconstruction. Measurements with a scanning robotic arm make it
possible to circumvent uncertainty due to positioning and transducer mismatch,
and examine the accuracy of the reconstruction over extended regions of space.
The results indicate that near perfect reconstructions are possible at low
frequencies, even from a limited set of measurements. In addition, the study
shows that it is possible to reconstruct damped room responses with reasonable
accuracy well into the mid-frequency range.
PMID- 29960502
TI - Understanding deep-water striation patterns and predicting the waveguide
invariant as a distribution depending on range and depth.
AB - The Waveguide Invariant (WI) theory has been introduced to quantify the
orientation of the intensity interference patterns in a range-frequency domain.
When the sound speed is constant over the water column, the WI is a scalar with
the canonical value of 1. But, when considering shallow waters with a stratified
sound speed profile, the WI ceases to be constant and is more appropriately
described by a distribution, which is mainly sensitive to source/receiver depths.
Such configurations have been widely investigated, with practical applications
including passive source localization. However, in deep waters, the interference
pattern is much more complex and variable. In fact the observed WI varies with
source/receiver depth but it also varies very quickly with source-array range. In
this paper, the authors investigate two phenomena responsible for this
variability, namely the dominance of the acoustic field by groups of modes and
the frequency dependence of the eigenmodes. Using a ray-mode approach, these two
features are integrated in a WI distribution derivation. Their importance in deep
water is validated by testing the calculated WI distribution against a reference
distribution directly measured on synthetic data. The proposed WI derivation
provides a thorough way to predict and understand the striation patterns in deep
water context.
PMID- 29960503
TI - Acoustically induced cavity cloud generated by air-gun arrays-Comparing video
recordings and acoustic data to modeling.
AB - For seismic air-gun arrays, ghost cavitation is assumed to be one of the main
mechanisms for high-frequency signal generation. Ghost cavitation signals are
weak for seismic frequencies (<300 Hz) and do not contribute to seismic
reflection profiling. In the current experiment, the ghost cavity cloud is
monitored by a high-speed video camera using 120 frames per second. This is, as
far as the authors know, the first convincing photographic evidence of ghost
induced cavitation. In addition to video recording, acoustic signals were
recorded with a sampling rate of 312.5 kHz using broadband hydrophones suspended
17 m below the array. The pressure drop around the source array is estimated
using air-gun modeling followed by a phenomenological modeling of the growth and
collapse of each vapor cavity. The cumulative effect of cavity collapses is
modeled based on linear superposition of the acoustic signals generated by
individual cavities. The simulated acoustic ghost cavitation signal and the
corresponding cavity cloud show good agreement with the field data.
PMID- 29960504
TI - Effect of stimulus type and pitch salience on pitch-sequence processing.
AB - Using a same-different discrimination task, it has been shown that discrimination
performance for sequences of complex tones varying just detectably in pitch is
less dependent on sequence length (1, 2, or 4 elements) when the tones contain
resolved harmonics than when they do not [Cousineau, Demany, and Pessnitzer
(2009). J. Acoust. Soc. Am. 126, 3179-3187]. This effect had been attributed to
the activation of automatic frequency-shift detectors (FSDs) by the shifts in
resolved harmonics. The present study provides evidence against this hypothesis
by showing that the sequence-processing advantage found for complex tones with
resolved harmonics is not found for pure tones or other sounds supposed to
activate FSDs (narrow bands of noise and wide-band noises eliciting pitch
sensations due to interaural phase shifts). The present results also indicate
that for pitch sequences, processing performance is largely unrelated to pitch
salience per se: for a fixed level of discriminability between sequence elements,
sequences of elements with salient pitches are not necessarily better processed
than sequences of elements with less salient pitches. An ideal-observer model for
the same-different binary-sequence discrimination task is also developed in the
present study. The model allows the computation of d' for this task using
numerical methods.
PMID- 29960505
TI - Perceptual evaluation of measures of spectral variance.
AB - In many applications, it is desirable to achieve a signal that is as close as
possible to ideal white noise. One example is in the design of an artificial
reverberator, whereby there is a need for its lossless prototype output from an
impulse input to be perceptually white as much as possible. The Ljung-Box test,
the Drouiche test, and the Wiener Entropy-also called the Spectral Flatness
Measure-are three well-known methods for quantifying the similarity of a given
signal to ideal white noise. In this paper, listening tests are conducted to
measure the Just Noticeable Difference (JND) on the perception of white noise,
which is the JND between ideal Gaussian white noise and noise with a specified
deviation from the flat spectrum. This paper reports the JND values using one of
these measures of whiteness, which is the Ljung-Box test. This paper finds
considerable disagreement between the Ljung-Box test and the other two methods
and shows that none of the methods is a significantly better predictor of
listeners' perception of whiteness. This suggests a need for a whiteness test
that is more closely correlated to human perception.
PMID- 29960506
TI - Experimental investigations on sound energy propagation in acoustically coupled
volumes using a high-spatial resolution scanning system.
AB - The aim of this work is to study the sound field distribution in an experimental
scale-model of two coupled rooms. An automatic scanning mechanism moves a
microphone in small grid steps to measure room impulse responses at each grid
point. The measurements cover the entire two-dimensional area of the coupled
rooms. Sound energy distributions can be analyzed in the form of animated visual
displays, revealing sound propagation across the coupling aperture and inside
each room. This paper describes the measurement results, and the analysis method,
which offer deep insights into the temporal development of a sound field in
coupled spaces.
PMID- 29960507
TI - Microstructure design of lightweight fibrous material acting as a layered damper
for a vibrating stiff panel.
AB - Based on the idea that a layer of properly designed and manufactured fibrous
material can serve as both a sound absorber and a structural damper, an approach
is introduced in this article to design the microstructure of a fibrous layer for
it to provide optimal damping performance. To begin with, previous work related
to structural damping by fibrous layers was reviewed. Then the most appropriate
models from the literature were adapted for use in the current study. A system
comprising an aluminum panel and a limp fibrous layer was driven by a line force,
and both the spatial velocity response of the panel and the power distribution
within the system were calculated to quantify the degree of damping provided by
the fibrous layer, which helped identify the airflow resistivity that provides
optimal damping for any frequency and panel of interest. Given the optimal
airflow resistivity, a model relating fiber microstructure to airflow resistivity
was used to infer the optimal microstructure required to achieve the optimal
damping performance. One finding of the current work, for example, was that as
the target frequency was reduced, the fiber size required to achieve the optimal
damping performance increased.
PMID- 29960508
TI - Discrimination bandwidths for amplitude modulated and quasi-frequency modulated
tones with spectral cues degraded by a roving-level.
AB - Theoretically, discriminating an amplitude modulated tone (AM) from a quasi
frequency modulated tone (QFM) is an ideal task for measuring the bandwidth of
phase sensitivity because the stimuli have identical amplitude spectra but
different phase spectra. The stimuli are perfectly discriminable at narrow
bandwidths, but become indistinguishable at wide bandwidths. Measurements,
however, are thought to be compromised by auditory distortion products,
particularly a cubic distortion tone which interacts with the lower sideband of
the stimulus to create an intensity cue. The results and implications of using a
roving level procedure to eliminate distortion product effects are discussed.
PMID- 29960509
TI - Magnetic monitoring of a small Foucault pendulum.
AB - A three-axis magnetometer is used to measure the precession angle of a small
Foucault pendulum of 65.4 cm length and period 1.623 s. The swinging brass bob (4
kg) contains a small neodymium magnet to detect and sustain its motion. A
microcontroller is used to control electronics that drive the pendulum while
sampling the time-dependent magnetic field from the swinging bob. These data are
used to calculate the precession angle for each pendulum period. Long-term
studies demonstrated a precession rate of 10.31 degrees /h which is within 0.5%
of that expected for the latitude of the experiment. Considerable short-term
variation in the precession rate is observed (1.5 degrees /h) which is correlated
with the structure of the pendulum mechanics. The angle measurement noise is
found to be 0.059 degrees which enables a clear detection of the earth's
rotation with only 26.7 s of observation.
PMID- 29960510
TI - Inter-satellite laser link acquisition with dual-way scanning for Space Advanced
Gravity Measurements mission.
AB - Laser link acquisition is a key technology for inter-satellite laser ranging and
laser communication. In this paper, we present an acquisition scheme based on the
differential power sensing method with dual-way scanning, which will be used in
the next-generation gravity measurement mission proposed in China, called Space
Advanced Gravity Measurements (SAGM). In this scheme, the laser beams emitted
from two satellites are power-modulated at different frequencies to enable the
signals of the two beams to be measured distinguishably, and their corresponding
pointing angles are determined by using the differential power sensing method. As
the master laser beam and the slave laser beam are decoupled, the dual-way
scanning method, in which the laser beams of both the master and the slave
satellites scan uncertainty cones simultaneously and independently, can be used,
instead of the commonly used single-way scanning method, in which the laser beam
of one satellite scans and that of the other one stares. Therefore, the
acquisition time is reduced significantly. Numerical simulation and experiments
of the acquisition process are performed using the design parameters of the SAGM
mission. The results show that the average acquisition time is less than 10 s for
a scanning range of 1-mrad radius with a success rate of more than 99%.
PMID- 29960511
TI - Note: Measurement of the cathode layer thickness in glow discharges with a
Langmuir probe.
AB - A method using a Langmuir probe to determine the thickness of the cathode layer
for a glow discharge is developed. The method is based on the phenomenon that the
curve of the voltage-current characteristics changes in shape as the Langmuir
probe moves from the positive column into the cathode layer. The method was used
to measure the thicknesses of the cathode layer in the normal glow discharges of
argon and air with the cathodes made from stainless steel and aluminum. The
results are in good agreement with those given in a book of gas discharge.
PMID- 29960512
TI - Impedance measurement system for automatic determination of glycated hemoglobin.
AB - In this study, an automatic glycated hemoglobin (HbA1c) impedance measurement
system (AHMS) is developed for the detection of HbA1c. The proposed device
removes some of the drawbacks of common instruments for HbA1c detection (i.e.,
large, expensive, difficult to operate) by detecting the ratio of HbA1c to Hb.
The method is label-free and requires only a small sample volume; no additional
reagents are required. The manpower consumption and bulk of the instrument are
also reduced. The method provides a simple way to analyze impedance deviation and
effectively reduces the effort required by the operator. The ratios of HbA1c to
Hb (4%-7%) are well distinguished, and the experiment is used to build a database
for AHMS. To check the reliability of the proposed system, a sample test using
three different ratios of HbA1c is applied in this study. The sample test uses
HbA1c to Hb ratios of 4.7%, 5.6%, and 6.8%, and the determined experimental
values are 4.93%, 5.8%, and 6.83%, respectively. The sample test has an accuracy
of approximately 96.99%. Based on these results, the proposed system for
detecting HbA1c through protein coverage is both effective and feasible.
PMID- 29960513
TI - An enhanced broad-frequency-band apparatus for dynamic measurement of elastic
moduli and Poisson's ratio of rock samples.
AB - We built a broad-frequency-band measurement system for rock elastic parameters
based on the stress-strain method following Batzle et al., Geophysics 71, N1-N9
(2006). The system gives strain amplitude anomalies at some measurement
frequencies. These anomalies put limitations on the range of the measurement
frequency and jeopardize the credibility of the measurement results over a broad
frequency band. To overcome these limitations, we investigated the cause of these
anomalous strains by numerical model simulations with a finite element method
based on the experimental apparatus. Through the systematic analysis of the
modeling results, we conclude that the resonances caused by non-axial
perturbations lead to such anomalous measurement results. Based on the analysis,
we give a solution to reduce the effect of the resonances and shift the first
resonance frequency beyond the frequency band of 1-2000 Hz. The enhanced
measurement system can provide robust and reliable measurements on the elastic
parameters of rocks between 1 and 2000 Hz, which is crucial for a quantitative
study of the frequency-dependent phenomenon related to fluid effects. This in
turn will provide a powerful tool for the experimental characterization of
elastic properties of oil/gas reservoir rocks, thus laying a solid foundation for
low-frequency rock physics analysis and quantitative seismic interpretation.
PMID- 29960514
TI - A multi-channel high-speed magnetic field detection system based on FPGA for
transcranial magnetic stimulation.
AB - Transcranial magnetic stimulation (TMS), a popular technology, acts on the brain
by using a pulse magnetic field to cause a series of physiological and
biochemical reactions. In order to detect the magnetic field generated by the TMS
coil with high-speed and multi-channel performance, a novel magnetic field
detection system based on a field programmable gate array (FPGA) is designed and
implemented. The detection system includes an induction coil array, a data
acquisition (DAQ) card, and upper computer monitor software. The DAQ card
contains analog signal processing circuits, a multiplexer, an analog-to-digital
converter, and a FPGA with a high-speed, parallel, and switching idea. The system
can sample at a rate of 500 ksps, with 14-bit resolution and 12 channels. The
three dimensional (3D) magnetic field can be monitored on the screen with a
waveform display and 3D magnetic field vector display. The DAQ card has a good
signal noise and distortion and cross talk of 88.35 dB and -79.69 dB,
respectively. Compared with the NI DAQ card, the proposed system has a relative
error smaller than 1.81% and a mean square error smaller than 2.89 * 10-6, which
verifies that the proposed detection system has a good performance. The multi
channel high-speed magnetic field detection system provides an important platform
for the study of TMS in medical, engineering, and other fields.
PMID- 29960516
TI - A novel trigger for pseudospark switch with high repetition rate, low jitter, and
compact structure.
AB - This paper presents the design and development of a trigger with a high
repetition rate, low jitter, and compact structure for the pseudospark switch
(PSS), which includes an improved Marx generator based on avalanche transistors
and a corona-plasma trigger unit. The generator adopted a novel 3 * 12-stage Marx
circuit based on avalanche transistors in which the failure rate of transistors
in the first and second stages was significantly reduced by connecting the
parallel capacitors compared to the previous similar generator. The reason for
the improved performance was also discussed. The main parameters of output pulses
were an amplitude of -7 kV, rise time of 6 ns, jitter of 0.2 ns, and repetition
rate of 2 kHz. The corona-plasma trigger unit adopted BaTiO3 ceramics with high
epsilonr as the dielectric and was arranged in the hollow cathode of the PSS. The
experiments of triggering a PSS prototype were conducted. The influence of anode
voltage and pressure on the trigger delay and jitter was studied, and the minimum
trigger jitter achieved <1 ns. This trigger worked for 107 shots at the
repetition rate of 2 kHz continuously without obvious performance degradation and
any failure of the generator. The main advantage of this trigger is the
simultaneous combination of the high repetition rate, low jitter, long lifetime,
and great simplicity in a compact structure.
PMID- 29960515
TI - Characterisation of a sub-20 ps temporal resolution pulse dilation
photomultiplier tube.
AB - A pulse-dilation photomultiplier tube (PD-PMT) with sub-20 ps temporal resolution
has been developed for use with gamma-ray-sensitive gas Cherenkov detectors at
the National Ignition Facility to improve the diagnosis of nuclear fusion burn
history and the areal density of the remaining capsule ablator. The pulse
dilation mechanism entails the application of a time-dependent, ramp waveform to
a photocathode-mesh structure, introducing a time-dependent photoelectron
accelerating potential. The electric field imparts axial velocity dispersion to
outgoing photoelectrons. The photoelectron pulse is dilated as it transits a
drift region prior to amplification in a microchannel plate and read out with a
digital oscilloscope. We report the first measurements with the prototype PD-PMT
demonstrating nominal <20 ps FWHM across a 400 ps measurement window and <30 ps
FWHM for an extracted charge up to 300 pC. The output peak areas are linear to
within 20% over 3 orders of magnitude of input intensity. 3D particle in cell
simulations, which included space charge effects, have been carried out to
investigate the device temporal magnification, resolution, and linearity.
PMID- 29960517
TI - Application of the space-resolving flux detector for radiation measurements from
an octahedral-aperture spherical hohlraum.
AB - Space-resolving flux detection is an important technique for the diagnostic of
the radiation field within the hohlraum in inertial confinement fusion,
especially for the radiation field diagnostic in the novel spherical hohlraum
with octahedral six laser entrance holes (LEHs), where localized measurements are
necessary for the discrimination of the radiation flux from different LEHs. A
novel space-resolving flux detector (SRFD) is developed at the SG-III laser
facility for the radiation flux measurement in the first campaign of the
octahedral spherical hohlraum energetics experiment. The principle and
configuration of the SRFD system is introduced. The radiation flux from the wall
of a gas-filled octahedral spherical hohlraum is measured for the first time by
placing the SRFD system at the equatorial position of the SG-III laser facility,
aiming at the hohlraum wall through one of the six LEHs. The absolute radiation
flux from the re-emission area on the hohlraum wall is measured, and good
consistency is found between the experimental data and the calculated data from a
three-dimensional view factor analysis.
PMID- 29960518
TI - An ultra-high vacuum scanning tunneling microscope operating at sub-Kelvin
temperatures and high magnetic fields for spin-resolved measurements.
AB - We present the construction and performance of an ultra-low-temperature scanning
tunneling microscope (STM), working in ultra-high vacuum (UHV) conditions and in
high magnetic fields up to 9 T. The cryogenic environment of the STM is generated
by a single-shot 3He magnet cryostat in combination with a 4He dewar system. At a
base temperature (300 mK), the cryostat has an operation time of approximately 80
h. The special design of the microscope allows the transfer of the STM head from
the cryostat to a UHV chamber system, where samples and STM tips can be easily
exchanged. The UHV chambers are equipped with specific surface science treatment
tools for the functionalization of samples and tips, including high-temperature
treatments and thin film deposition. This, in particular, enables spin-resolved
tunneling measurements. We present test measurements using well-known samples and
tips based on superconductors and metallic materials such as LiFeAs, Nb, Fe, and
W. The measurements demonstrate the outstanding performance of the STM with high
spatial and energy resolution as well as the spin-resolved capability.
PMID- 29960519
TI - Tunable VUV photochemistry using vacuum ultraviolet free electron laser combined
with H-atom Rydberg tagging time-of-flight spectroscopy.
AB - In this article, we describe an experimental setup for studying tunable vacuum
ultraviolet photochemistry using the H-atom Rydberg tagging time-of-flight
technique. In this apparatus, two vacuum ultraviolet laser beams were used: one
is generated by using a nonlinear four-wave mixing scheme in a Kr gas cell and
fixed at 121.6 nm wavelength to probe the H-atom product through the Lyman alpha
transition and the other beam, produced by a seeded free electron laser facility,
can be continuously tunable for photodissociating molecules in the wavelength
range of 50-150 nm with extremely high brightness. Preliminary results on the H2O
photodissociation in the 4d (000) Rydberg state are reported here. These results
suggest that the experimental setup is a powerful tool for investigating
photodissociation dynamics in the vacuum ultraviolet region for molecules
involving H-atom elimination processes.
PMID- 29960520
TI - Amplitude-phase cross talk as a deterioration factor of signal-to-noise ratio in
phase-detection noise-cancellation technique for spectral pump/probe measurements
and compensation of the amplitude-phase cross talk.
AB - Noise cancellation of the light source is an important method to enhance the
signal-to-noise ratio (SNR) and facilitate high-speed detection in pump/probe
measurements. We developed a method to eliminate the noise for the multichannel
spectral pump/probe measurements with a spectral dispersion of a white probe
pulse light. In this method, the sample-induced intensity modulation is converted
to the phase modulation of the pulse repetition irrespective of the intensity
noise of the light source. The SNR is enhanced through the phase detection of the
observed signal with the signal synchronized to the pulse repetition serving as
the phase reference (synchronized signal). However, the shot-noise limited
performance is not achieved with an intense probe light. In this work, we
demonstrate that the performance limitation below the shot noise limit is caused
by the amplitude-phase cross talk. It converts the amplitude noise into the phase
noise and is caused by the space-charge effect in the photodetector, the reverse
bias voltage drop across the load impedance, and the phase detection circuit. The
phase delay occurs with an intense light at a PIN photodiode, whereas the phase
is advanced in an avalanche photodiode. Although the amplitude distortion
characteristics also reduce the performance, the distortion effect is equivalent
to the amplitude-phase cross talk. We also propose possible ways to compensate
the cross talk effect by using the phase modulation of the synchronized signal
for the phase detection based on the instantaneous amplitude.
PMID- 29960521
TI - Microwave magnetic field detection based on Cs vapor cell in free space.
AB - In this study, we demonstrate the direct measurement of a microwave (MW) magnetic
field through the detection of atomic Rabi resonances with Cs vapor cells in a
free-space low-Q cavity. The line shape (amplitude and linewidth) of detected
Rabi resonances is investigated versus several experimental parameters such as
the laser intensity, cell buffer gas pressure, and cell length. The specially
designed low-Q cavity creates a suitable MW environment allowing easy testing of
different vapor cells with distinct properties. Obtained results are analyzed to
optimize the performances of a MW magnetic field sensor based on the present atom
based detection technique.
PMID- 29960522
TI - Linear least-squares method for global luminescent oil film skin friction field
analysis.
AB - A data analysis method based on the linear least-squares (LLS) method was
developed for the extraction of high-resolution skin friction fields from global
luminescent oil film (GLOF) visualization images of a surface in an aerodynamic
flow. In this method, the oil film thickness distribution and its spatiotemporal
development are measured by detecting the luminescence intensity of the thin oil
film. From the resulting set of GLOF images, the thin oil film equation is solved
to obtain an ensemble-averaged (steady) skin friction field as an inverse
problem. In this paper, the formulation of a discrete linear system of equations
for the LLS method is described, and an error analysis is given to identify the
main error sources and the relevant parameters. Simulations were conducted to
evaluate the accuracy of the LLS method and the effects of the image patterns,
image noise, and sample numbers on the results in comparison with the previous
snapshot-solution-averaging (SSA) method. An experimental case is shown to enable
the comparison of the results obtained using conventional oil flow visualization
and those obtained using both the LLS and SSA methods. The overall results show
that the LLS method is more reliable than the SSA method and the LLS method can
yield a more detailed skin friction topology in an objective way.
PMID- 29960523
TI - Instrumentation for in situ flow electrochemical Scanning Transmission X-ray
Microscopy (STXM).
AB - We report the design and performance of a 3-electrode device for real time in
situ scanning transmission X-ray microscopy studies of electrochemical processes
under both static (sealed, non-flow) conditions and with a continuous flow of
electrolytes. The device was made using a combination of silicon microfabrication
and 3D printing technologies. The performance is illustrated by results of a
study of copper deposition and stripping at a gold working electrode. X-ray
absorption spectromicroscopy at the Cu 2p edge was used to follow the evolution
as a function of potential and time of the spatial distributions of Cu(0) and
Cu(i) species electro-deposited from an aqueous solution of copper sulphate. The
results are interpreted in terms of competing mechanisms for the reduction of
Cu(ii).
PMID- 29960524
TI - Developing a solid-state quasi-square pulse Marx generator.
AB - A solid-state quasi-square pulse Marx generator has been designed, constructed,
and tested in this paper. The spark gap switches of a typical Marx generator have
been replaced by a fractional-turn ratio saturable pulse transformer (FRSPT), and
a three-section anti-resonance network has taken the role of pulse forming module
in this quasi-square Marx generator. For the switches, thyristors are used as the
primary switches and the FRSPT is used as the pulse modulating switch. The
experimental results show that if the charge voltage is about 1000 V, the output
quasi-square pulse has an amplitude of 18.5 kV and a pulse width of 3.15 MUs, and
the experimental results verify the feasibility of the concept of an all-solid
state quasi-square square pulse Marx generator based on an FRSPT and anti
resonance network.
PMID- 29960525
TI - Calibration of micro-capacitance measurement system for thermal barrier coating
testing.
AB - In order to comprehensively evaluate the thermal barrier coating system of an
engine blade, an integrated planar sensor combining electromagnetic coils with
planar capacitors is designed, in which the capacitance measurement accuracy of
the planar capacitor is a key factor. The micro-capacitance measurement system is
built based on an impedance analyzer. Because of the influence of non-ideal
factors on the measuring system, there is an obvious difference between the
measured value and the actual value. It is necessary to calibrate the measured
results and eliminate the difference. In this paper, the measurement model of a
planar capacitive sensor is established, and the relationship between the
measured value and the actual value of capacitance is deduced. The model
parameters are estimated with the least square method, and the calibration
accuracy is evaluated with experiments under different dielectric conditions. The
capacitance measurement error is reduced from 29% ~ 46.5% to around 1% after
calibration, which verifies the feasibility of the calibration method.
PMID- 29960526
TI - Development of a radiative heating facility for studying flow and heat transfer
in hydrocarbon-cooled structures.
AB - An experimental facility was designed to simulate the heat exchange between the
hot gas and the fuel-cooled wall in a scramjet combustor. Thermal radiation from
an electrically heated graphite plate is employed to unilaterally heat up a multi
channeled cooling plate. A maximum heat flux of over 0.8 MW/m2 was achieved for
an effective heating area up to 1000 mm * 40 mm. Precise control of the back
pressure of a coolant (up to 5 MPa) in a unique way was also demonstrated. With
this facility, studies of flow and heat transfer in hydrocarbon-cooled structures
can be performed under a well-controlled manner.
PMID- 29960527
TI - Ultra-broadband coplanar waveguide for optically detected magnetic resonance of
nitrogen-vacancy centers in diamond.
AB - We report on coplanar waveguides (CPWs) designed for optically detected magnetic
resonance of nitrogen-vacancy (NV) centers in diamonds. A broad band up to 15.8
GHz has been realized, which ensures that the electron spins can be manipulated
under external magnetic fields up to 5000 G. The conversion factor of CPW has
been measured by Rabi nutation experiments, which ranges from 6.64 G W-1/2 to
10.60 G W-1/2 in the frequency band from 0.76 GHz to 17.3 GHz. Broadband CPWs
also provide high quality control pulses due to the minimization of the
distortion. These characteristics will find potential applications in NV-based
quantum information processing and single spin magnetometry.
PMID- 29960528
TI - Magnetically confined electron beam system for high resolution electron
transmission-beam experiments.
AB - A novel experimental setup has been implemented to provide accurate electron
scattering cross sections from molecules at low and intermediate impact energies
(1-300 eV) by measuring the attenuation of a magnetically confined linear
electron beam from a molecular target. High-resolution electron energy is
achieved through confinement in a magnetic gas trap where electrons are cooled by
successive collisions with N2. Additionally, we developed and present a method to
correct systematic errors arising from energy and angular resolution limitations.
The accuracy of the entire measurement procedure is validated by comparing the N2
total scattering cross section in the considered energy range with benchmark
values available in the literature.
PMID- 29960529
TI - Velocity- and pointing-error measurements of a 300 000-r/min self-bearing
permanent-magnet motor for optical applications.
AB - Compact, ultra-high-speed self-bearing permanent-magnet motors enable a wide
scope of applications including an increasing number of optical ones. For
implementation in an optical setup, the rotors have to satisfy high demands
regarding their velocity and pointing errors. Only a restricted number of
measurements of these parameters exist and only at relatively low velocities.
This manuscript presents the measurement of the velocity and pointing errors at
rotation frequencies up to 5 kHz. The acquired data allow us to identify the
rotor drive as the main source of velocity variations with fast fluctuations of
up to 3.4 ns (RMS) and slow drifts of 23 ns (RMS) over ~120 revolutions at 5 kHz
in vacuum. At the same rotation frequency, the pointing fluctuated by 12 MUrad
(RMS) and 33 MUrad (peak-to-peak) over ~10 000 round trips. To our best
knowledge, this states the first measurement of velocity and pointing errors at
multi-kHz rotation frequencies and will allow potential adopters to evaluate the
feasibility of such rotor drives for their application.
PMID- 29960530
TI - Note: Pulsed optically pumped atomic clock based on a paraffin-coated cell.
AB - We report on the implementation of a pulsed optically pumped atomic clock based
on a paraffin-coated cell. The relaxation times are measured, with the
longitudinal relaxation time, T1 = 9.7 +/- 0.4 ms, and the transversal relaxation
time, T2 = 0.40 +/- 0.03 ms. We demonstrated that the measured frequency
stability of the clock is 3.9 * 10-13 tau-1/2 (1 s <= tau <= 100 s) and reaches a
value of 3.1 * 10-14 for tau = 1000 s, where tau is the averaging time. This is
an unprecedented result for a paraffin-coated vapor cell clock, and it makes
significant contributions toward improving the performance of the wall-coated
vapor cell atomic clock.
PMID- 29960531
TI - Experimental setup for the study of resonant inelastic X-ray scattering of
organometallic complexes in gas phase.
AB - A new setup has been designed and built to study organometallic complexes in gas
phase at the third-generation Synchrotron radiation sources. This setup consists
of a new homemade computer-controlled gas cell that allows us to sublimate solid
samples by accurately controlling the temperature. This cell has been developed
to be a part of the high-resolution X-ray emission spectrometer permanently
installed at the GALAXIES beamline of the French National Synchrotron Facility
SOLEIL. To illustrate the capabilities of the setup, the cell has been
successfully used to record high-resolution Kalpha emission spectra of gas-phase
ferrocene Fe(C5H5)2 and to characterize their dependence with the excitation
energy. This will allow to extend resonant X-ray emission to different
organometallic molecules.
PMID- 29960532
TI - High-density convergent plasma sputtering device for a liquid metal target using
an unheated glass plate.
AB - A high-density convergent plasma sputtering device has been developed for a
liquid metal target, using an unheated glass plate. The convergent magnetic field
lines, which are produced by an external solenoid coil and a permanent magnet
positioned behind the liquid metal target, effectively transport high-density
plasmas near the target. In this study, a liquid gallium target was sputtered
with nitrogen plasmas, without additive gas required for depositing gallium
nitride films on the unheated substrates. The deposition rate of the GaN film was
estimated at ~13 nm/min at a gas pressure of 0.2 Pa. A strong diffraction peak
was observed along the GaN (002) axis, with the use of an unheated glass plate
and a target-substrate distance of ~45 mm.
PMID- 29960533
TI - Large field of view imaging system for remote target capture and trajectory
measurement based on cone rotation.
AB - In the remote target trajectory measurement system, because of the size
limitation of the image sensor, the angle of view of the current telephoto camera
is very small, which cannot meet the requirements of target acquisition. After
comparing the current large-field imaging methods, a scheme of a large field of
view (FoV) and high frame rate scanning by controlling the camera to perform
conical rotation is proposed, and a 3 * 3 external FoV stitching system that
includes the scheme is designed. An experimental prototype was constructed to
verify the system. In this paper, the mechanical structure of the prototype, the
camera exposure control flow, and the image data processing flow are introduced,
and the imaging motion feature of the prototype caused by the camera exposure
during conical motion is analyzed. In the experiment, the prototype controlled
the camera accurately exposed to the sub-fields. Using a camera with an angle of
view of 0.78 degrees , a large angle of view system of 2.23 degrees was obtained
by FoV stitching. The system we present is less difficult to implement and has
obvious advantages in volume and weight compared to multi-camera arrays. It is
suitable for engineering applications in remote target measurement system.
PMID- 29960534
TI - A method to eliminate the influence of incident light variations in spectral
analysis.
AB - The intensity of the light source and consistency of the spectrum are the most
important factors influencing the accuracy in quantitative spectrometric
analysis. An efficient "measuring in layer" method was proposed in this paper to
limit the influence of inconsistencies in the intensity and spectrum of the light
source. In order to verify the effectiveness of this method, a light source with
a variable intensity and spectrum was designed according to Planck's law and
Wien's displacement law. Intra-lipid samples with 12 different concentrations
were prepared and divided into modeling sets and prediction sets according to
different incident lights and solution concentrations. The spectra of each sample
were measured with five different light intensities. The experimental results
showed that the proposed method was effective in eliminating the influence caused
by incident light changes and was more effective than normalized processing.
PMID- 29960535
TI - An efficient phase error self-compensation algorithm for nonsinusoidal gating
fringes in phase-shifting profilometry.
AB - The phase-shifting method is widely used in fringe projection profilometry. Since
both the digital light projector and camera used in a grating projection
measurement system are nonlinear pieces of equipment, the grating fringes
captured by using the camera do not have a good sinusoidal property, which leads
to a three-dimensional measurement error. Although the double-step phase-shifting
method has proved that the phase error can be reduced to a large extent, the
number of grating fringes is doubled, which affects the measurement efficiency.
In this paper, we present an efficient phase error self-compensation algorithm.
It transforms the initial wrapped phase into a second wrapped phase and
integrates the initial and second wrapped phases to reduce the phase error. The
advantage is that the measurement accuracy is close to that of the double-step
phase-shifting method without increasing the number of projection fringes; at the
same time, the measurement time is shortened, and the measurement efficiency is
improved. We have elaborated the proposed algorithm in detail and compared it
with the traditional single-step phase-shifting method and the double-step phase
shifting method. Finally, we utilize the proposed algorithm to measure different
objects. The results prove its effectiveness.
PMID- 29960536
TI - A stable pulsed power supply for multi-beamline XFEL operations.
AB - Since an X-ray Free Electron Laser (XFEL) facility is a linac-based single-user
machine, a multi-beamline mode of operation, which improves the efficiency of
user experiments, is critical for accommodating users' rapidly increasing demand
for beamtime. A key supporting technology is a highly stable pulsed power supply
(PS), which enables stable XFEL operations by precisely switching the beam route.
We developed a high-power pulsed PS to drive a kicker magnet installed in a
SACLA's beam switching system. SiC MOSFETs were adapted as switching elements to
reduce the required size and to increase the electric power efficiency. The PS we
developed provides two key capabilities: (i) a high current stability of 20 ppm
(peak-to-peak) at a peak power of 0.24 MW and (ii) generation of controllable,
bipolar, and trapezoidal current waveforms at 60 Hz. This paper describes the
overall concept, the detailed design, the performance achieved, and the initial
beam test results.
PMID- 29960537
TI - Publisher's Note: "Sub-millisecond electron density profile measurement at the
JET tokamak with the fast lithium beam emission spectroscopy system" [Rev. Sci.
Instrum. 89, 043509 (2018)].
PMID- 29960538
TI - Design and analysis of a centripetal force type-magnetic bearing for a flywheel
battery system.
AB - In this study, a novel centripetal force type-magnetic bearing (CFT-MB) for a
flywheel battery system is proposed. First, the configuration, magnetic circuits,
and working principles of the CFT-MB are analyzed in detail. Then, a backward
step-by-step method based on magnetic field division is adopted for the parameter
design. In addition, the proposed CFT-MB prototype is simulated and manufactured
based on the design results. The simulation result verifies the accuracy of
parameter design results and the superiority performance of the CFT-MB. Finally,
the experiments and tests of the stiffness and gyroscopic effects are conducted.
The experimental results show that the presented CFT-MB has superior performance
than the traditional cylindrical magnetic bearing, and the gyroscopic effect can
be obviously suppressed by adopting the CFT-MB.
PMID- 29960539
TI - Partial compensation interferometry measurement system for parameter errors of
conicoid surface.
AB - Surface parameters, such as vertex radius of curvature and conic constant, are
used to describe the shape of an aspheric surface. Surface parameter errors
(SPEs) are deviations affecting the optical characteristics of an aspheric
surface. Precise measurement of SPEs is critical in the evaluation of optical
surfaces. In this paper, a partial compensation interferometry measurement system
for SPE of a conicoid surface is proposed based on the theory of slope
asphericity and the best compensation distance. The system is developed to
measure the SPE-caused best compensation distance change and SPE-caused surface
shape change and then calculate the SPEs with the iteration algorithm for
accuracy improvement. Experimental results indicate that the average relative
measurement accuracy of the proposed system could be better than 0.02% for the
vertex radius of curvature error and 2% for the conic constant error.
PMID- 29960540
TI - Test bed for contact-mode triboelectric nanogenerator.
AB - The triboelectric nanogenerator (TENG) has become one of the strongest candidates
for sustainable power sources. The power of a TENG depends on factors such as
contact area, contact parallelism, contact force, and contact speed. In order to
evaluate the performance of the TENG precisely and quantitatively, it is
necessary to apply consistent experimental conditions and measurement processes.
In this paper, we propose a test bed capable of adjusting the contact area and
contact parallelism and measuring the contact force, contact speed, current, and
voltage in real time. The test bed consists of a 2-axis planar stage, a 2-axis
tilting stage, a 1-axis vertical stage, a 3-degree-of-freedom (DOF) force/torque
sensor, a capacitive displacement sensor, and a voice coil actuator. The 3-DOF
force/torque sensor can provide feedback on the degree of parallelism and contact
area alignment as well as contact force. With the proposed test bed, the effects
of parallelism error, contact area, contact force, and contact speed on the
performance of contact-mode TENGs are quantitatively analyzed. This test bed is
expected to be used for the quantitative analysis of contact-mode TENGs with
various new structures and for comparison among different devices.
PMID- 29960541
TI - Microwave probe stations with three-dimensional control of the magnetic field to
study high-frequency dynamics in nanoscale devices.
AB - We present two microwave probe stations with motorized rotary stages for
adjusting the magnitude and angle of the applied magnetic field. In the first
system, the magnetic field is provided by an electromagnet and can be adjusted
from 0 to ~1.4 T while its polar angle (theta) can be varied from 0 degrees to
360 degrees . In the second system, the magnetic field is provided by a Halbach
array permanent magnet, which can be rotated and translated to cover the full
range of polar (theta) and azimuthal (phi) angles with a tunable field magnitude
up to ~1 T. Both systems are equipped with microwave probes, bias-Ts, amplifiers,
and spectrum analyzers to allow for microwave characterization up to 40 GHz, as
well as software to automatically perform continuous large sets of electrical and
microwave measurements.
PMID- 29960542
TI - Note: Temperature-frequency calibration method based on spectral analysis for QCR
dew point sensor.
AB - Each quartz crystal resonator (QCR) shows different frequency behavior as a
function of temperature. To get the curve of the temperature effect compensation
during the dew-deposition process, we use the active controlled temperature type
of the QCR dew point sensor. In this note, a QCR temperature-frequency
calibration method based on spectral analysis is described. It combines FFT and
spectral refinement and the parameter table method to achieve high precision
frequency extraction. Frequency identification accuracy is 10-6. The results
showed that the method has a good performance in frequency extraction of the QCR
sensors.
PMID- 29960543
TI - Note: A well-confined pulsed low-energy ion beam: Test experiments of Ar.
AB - Here we report a pulsed low-energy ion beam source for ion-molecule reaction
study, in which the ions produced by the pulsed electron impact are confined well
in the spatial size of each bunch. In contrast to the ion focusing method to
reduce the transverse section of the beam, the longitudinal section in the
translational direction is compressed by introducing a second pulse in the ion
time-of-flight system. The test experiments for the low-energy argon ions are
performed. The present beam source is ready for applications in the ion-molecule
reaction dynamics experiments, in particular, in combination with the ion
velocity map imaging technique.
PMID- 29960544
TI - Design and test of a Faraday cup for low-charge measurement of electron beams
from laser wakefield acceleration.
AB - Nowadays, laser wakefield acceleration is considered to be one of the perspective
methods for GeV electron beam production. The combination of laser accelerated
electrons and Compton backscattering of a probe light beam opens the possibility
of creating the tabletop source of a femtosecond light beam in x-ray and gamma
ranges. The project is aimed at creating a laser-driven Compton light source in
ILP SB RAS in collaboration with BINP SB RAS. Production of 1-10 pC electron
beams in sub-ps time range duration with energies up to 100 MeV is expected to be
a result of the first stage of the project. Since the energy of electrons does
not exceed 100 MeV, it allows the use of the Faraday cup (FC) with reasonable
dimensions, instead of the commonly used integrating current transformer. The
geometry of the FC has been optimized taking into account beam stopping
simulation as well as a low capacity requirement. Simulation of high-frequency
properties of the entire system was carried out. The system has been tested at
the VEPP-5 electron linac. The results of developing and testing this FC are
presented.
PMID- 29960545
TI - The Heidelberg compact electron beam ion traps.
AB - Electron beam ion traps (EBITs) are ideal tools for both production and study of
highly charged ions (HCIs). In order to reduce their construction, maintenance,
and operation costs, we have developed a novel, compact, room-temperature design,
the Heidelberg Compact EBIT (HC-EBIT). Four already commissioned devices operate
at the strongest fields (up to 0.86 T) reported for such EBITs using permanent
magnets, run electron beam currents up to 80 mA, and energies up to 10 keV. They
demonstrate HCI production, trapping, and extraction of pulsed Ar16+ bunches and
continuous 100 pA ion beams of highly charged Xe up to charge state 29+, already
with a 4 mA, 2 keV electron beam. Moreover, HC-EBITs offer large solid-angle
ports and thus high photon count rates, e.g., in x-ray spectroscopy of
dielectronic recombination in HCIs up to Fe24+, achieving an electron-energy
resolving power of E/DeltaE > 1500 at 5 keV. Besides traditional on-axis electron
guns, we have also implemented a novel off-axis gun for laser, synchrotron, and
free-electron laser applications, offering clear optical access along the trap
axis. We report on its first operation at a synchrotron radiation facility
demonstrating the resonant photoexcitation of highly charged oxygen.
PMID- 29960546
TI - Note: Multi-sheet light enables optical interference lithography.
AB - We propose and demonstrate a modified spatial filter-based single-shot
lithography technique for fabricating an array of microfluidic channels. This is
achieved by illuminating the photopolymer specimen with a multiple light sheet
(MLS) pattern. Modified spatial filtering is employed in a cylindrical lens
system to generate the MLS pattern. The transmission window [the difference
(alpha - beta) angle] of the spatial filter determines the characteristics of the
pattern and the fabricated microfluidic channel array. After exposing to a
negative photoresist (DPHPA monomer with rose bengal as the photoinitiator), this
gives rise to an array of micro-fluidic channels (post development process). We
studied the effect of micro-channel geometry (channel width, inter-channel
separation, and aspect ratio) for varying exposure times that show near-linear
dependence. The results show that the fabricated array has 7 prominent channels
with an individual channel width and inter-channel separation of approximately 5
MUm and 12 MUm, respectively. The proposed technique enables selective plane
patterning and reduces the overall cost for large-scale production.
PMID- 29960547
TI - Demonstration of a chamber for strain mapping of steel specimens under mechanical
load in a hydrogen environment by synchrotron radiation.
AB - We demonstrate a hydrogen gas chamber suitable for lattice strain measurements
and capturing radiographs of a steel specimen under a mechanical load using high
energy synchrotron x-rays. The chamber is suitable for static and cyclic
mechanical loading. Experiments were conducted at the 1-ID-E end station of the
Advanced Photon Source, Argonne National Laboratory. Diffraction patterns show a
high signal-to-noise ratio suitable for lattice strain measurements for the
specimen and with minimal scattering and overlap from the gas chamber
manufactured from aluminum. In situ radiographs of a specimen in the hydrogen
chamber show the ability to track a growing crack and to map the lattice strain
around the crack with high spatial and strain resolution.
PMID- 29960548
TI - A fast response, low heat generating activation method for LHe level sensors.
AB - A superconducting liquid helium (LHe) level sensor of length 300 mm has been
fabricated based on the principle of differential heat transfer characteristic in
helium gas compared to that in liquid. The sensor wire used has a diameter of 38
MUm, and the wire was obtained from a pack of multifilament wires. A full thermo
electrical characterisation of the sensor was carried out in a dedicated setup.
Its dynamic thermal response was also studied to understand its timing
characteristics at different liquid levels and excitation currents. Based on the
sensor characterisation, a new level measurement technique is evaluated which can
reduce the heat load going to LHe during sensor activation without compromising
on its sensitivity or accuracy. The timing response with this technique will make
the level detection faster compared to the conventional techniques.
PMID- 29960549
TI - Stationary afterglow apparatus with CRDS for study of processes in plasmas from
300 K down to 30 K.
AB - A cryogenic stationary afterglow apparatus equipped with a near-infrared cavity
ring-down-spectrometer (Cryo-SA-CRDS) for studies of electron-ion recombination
processes in the plasma at temperatures 30-300 K has been designed, constructed,
tested, and put into operation. The plasma is generated in a sapphire discharge
tube that is contained in a microwave cavity. The cavity and the tube are
attached to the second stage of the cold head of the cryocooler system, and they
are inserted to an UHV chamber with mirrors for CRDS and vacuum windows on both
ends of the tube. The temperature of the discharge tube can be made as low as 25
K. In initial test measurements, the discharge was ignited in He/Ar/H2 or He/H2
gas mixtures and the density of H3+ ions and their kinetic and rotational
temperatures were measured during the discharge and afterglow. From the measured
decrease in the ion density, during the afterglow, effective recombination rate
coefficients were determined. Plasma relaxation was studied in He/Ar gas mixtures
by monitoring the presence of highly excited argon atoms. The spectroscopic
measurements demonstrated that the kinetic temperature of the ions is equal to
the gas temperature and that it can be varied from 300 K down to 30 K.
PMID- 29960550
TI - A 4 K FT-ICR cell for infrared ion spectroscopy.
AB - We present the design of the newly constructed cryogenic Fourier-transform ion
cyclotron resonance (FT-ICR) ion trap for infrared ion spectroscopy. Trapped ions
are collisionally cooled by the pulsed introduction of buffer gas into the cell.
Using different buffer gases and cell temperatures, we record action spectra of
weakly bound neutral gas-analyte complexes with an IR laser source. We show for
the first time that ion-He complexes can be observed in an ICR cell at
temperatures around 4 K. We compare the experimental vibrational spectra of
Ag(PPh3)2+ obtained by tagging with different neutral gases: He, Ne, Ar, H2, and
N2 to computed vibrational spectra. Furthermore, the conditions necessary for the
formation of neutral tags within an ICR ion trap are studied.
PMID- 29960551
TI - Scalable cryogenic readout circuit for a superconducting nanowire single-photon
detector system.
AB - The superconducting nanowire single-photon detector (SNSPD) is a leading
technology for quantum information science applications using photons, and is
finding increasing uses in photon-starved classical imaging applications.
Critical detector characteristics, such as timing resolution (jitter), reset
time, and maximum count rate, are heavily influenced by the readout electronics
that sense and amplify the photon detection signal. We describe a readout circuit
for SNSPDs using commercial off-the-shelf amplifiers operating at cryogenic
temperatures. Our design demonstrates a 35 ps timing resolution and a maximum
count rate of over 2 * 107 counts per second, while maintaining <3 mW power
consumption per channel, making it suitable for a multichannel readout.
PMID- 29960552
TI - Gaussian process tomography for soft x-ray spectroscopy at WEST without
equilibrium information.
AB - Gaussian process tomography (GPT) is a recently developed tomography method based
on the Bayesian probability theory [J. Svensson, JET Internal Report EFDA-JET
PR(11)24, 2011 and Li et al., Rev. Sci. Instrum. 84, 083506 (2013)]. By modeling
the soft X-ray (SXR) emissivity field in a poloidal cross section as a Gaussian
process, the Bayesian SXR tomography can be carried out in a robust and extremely
fast way. Owing to the short execution time of the algorithm, GPT is an important
candidate for providing real-time reconstructions with a view to impurity
transport and fast magnetohydrodynamic control. In addition, the Bayesian
formalism allows quantifying uncertainty on the inferred parameters. In this
paper, the GPT technique is validated using a synthetic data set expected from
the WEST tokamak, and the results are shown of its application to the
reconstruction of SXR emissivity profiles measured on Tore Supra. The method is
compared with the standard algorithm based on minimization of the Fisher
information.
PMID- 29960553
TI - Development of a hard X-ray split-and-delay line and performance simulations for
two-color pump-probe experiments at the European XFEL.
AB - A hard X-ray Split-and-Delay Line (SDL) under construction for the Materials
Imaging and Dynamics station at the European X-Ray Free-Electron Laser (XFEL) is
presented. This device aims at providing pairs of X-ray pulses with a variable
time delay ranging from -10 ps to 800 ps in a photon energy range from 5 to 10
keV for photon correlation and X-ray pump-probe experiments. A custom designed
mechanical motion system including active feedback control ensures that the high
demands for stability and accuracy can be met and the design goals achieved.
Using special radiation configurations of the European XFEL's SASE-2 undulator
(SASE: Self-Amplified Spontaneous Emission), two-color hard x-ray pump-probe
schemes with varying photon energy separations have been proposed. Simulations
indicate that more than 109 photons on the sample per pulse-pair and up to about
10% photon energy separation can be achieved in the hard X-ray region using the
SDL.
PMID- 29960554
TI - In situ measurements of the spectral reflectance of metallic mirrors at the
Halpha line in a low density Ar-H plasma.
AB - The efficient and reliable control and monitoring of the quality of the optical
properties of mirrors is an open problem in laboratory plasmas. Until now, the
measurement of the reflectance of the first mirrors was based on the methods that
require additional light calibration sources. We propose a new technique based on
the ratio of the red- and blue-shifted emission signals of the reflected hydrogen
atoms which enables the in situ measurement of the spectral reflectance of
metallic mirrors in low-density Ar-H or Ar-D plasmas. The spectral reflectance
coefficients were measured for C, Al, Ag, Fe, Pd, Ti, Sn, Rh, Mo, and W mirrors
installed in the linear magnetized plasma device PSI-2 operating in the pressure
range of 0.01-0.1 Pa. The results are obtained for the Halpha line using the
emission of fast atoms induced by excitation of H atoms through Ar at a plasma
solid interface by applying a negative potential U = -80, ..., -220 V to the
mirror. The agreement between the measured and theoretical data of reflectance is
found to be within 10% for the investigated materials (except for C). The spectra
also allow us to efficiently determine the material of the mirror.
PMID- 29960555
TI - Octave bandwidth hybrid-coupled microstrip diplexer for a broadband radio
astronomy receiver.
AB - A new octave bandwidth high selectivity compact microstrip diplexer working in
the band from 10 to 20 GHz is presented, intended to be a part of an electro
optical interferometer covering the whole frequency band. The circuit is based on
the combination of hybrid couplers and bandpass filters both on the microstrip
technology. The diplexer provides two output frequency bands which cover the 10
14 GHz (relative bandwidth of 33%) and the 16-20 GHz (relative bandwidth of 22%)
ranges, respectively, with a stop band in between from 14 to 16 GHz. Measured
results show a insertion loss level of 3.3 dB for both output bands and high
selectivity performance, exhibiting a rejection level between output bands higher
than 20 dB and return loss better than 10 dB in all ports.
PMID- 29960556
TI - A fiber-optic bolometer based on a high-finesse silicon Fabry-Perot
interferometer.
AB - We report a fiber-optic bolometer based on a high-finesse silicon Fabry-Perot
interferometer (FPI). The silicon FPI absorbs and converts the incident radiation
into temperature variations, which are interrogated by the shift of the
reflection spectrum of the FPI. The FPI is a silicon pillar with one side coated
with a high-reflectivity dielectric mirror and the other side coated with a gold
mirror. A multimode fiber collimator is applied between the FPI and lead-in
single-mode fiber to reduce the round-trip diffraction loss, giving rise to a
high-finesse of 35 of the FPI. The sensor is demodulated using a low-cost
distributed feedback diode laser. A dummy bolometer was used to effectively
reduce the common noises from the laser wavelength drift and ambient temperature
variations. Experimental results show that, compared with a previously reported
fiber-optic bolometer, the one reported here has a 5-fold decrease in noise and a
7-fold increase in responsivity with a noise equivalent power density (NEPD) of
0.27 W/m2, which is comparable with the NEPDs of the state-of-the-art resistive
bolometers.
PMID- 29960557
TI - A dedicated system for in situ testing of gamma ray induced optical absorption
and emission in optical materials.
AB - Serious radiation damage due to the high energy neutron/gamma fluxes is expected
for optical materials such as scintillators, windows, and lenses which will be
part of the plasma diagnostics in future fusion devices. Radiation induced
absorption represents a major concern for these components for which experimental
validation under as near as possible reactor conditions becomes essential. A new
experimental system has been developed at the CIEMAT Nayade 60Co gamma
irradiation facility for in situ radiation induced optical absorption
measurements, covering a spectral range between 370 and 730 nm. This setup
consists in a rotating sample holder which allows one to collect incident light
(reference signal) and transmitted light through the material to be tested as a
function of irradiation dose. This is an advanced and robust system which
overcomes the important experimental difficulties that radiation involves
providing a valuable testing capability for transmission components and
scintillators under realistic fusion conditions. A detailed description of the
experimental arrangement, together with preliminary tests carried out for system
validation is given in this paper.
PMID- 29960558
TI - 500 MHz resonant photodetector for high-quantum-efficiency, low-noise homodyne
measurement.
AB - We design and demonstrate a resonant-type differential photodetector for a low
noise quantum homodyne measurement at 500 MHz optical sideband with 17 MHz of
bandwidth. By using a microwave monolithic amplifier and a discrete voltage
buffer circuit, a low-noise voltage amplifier is realized and applied to our
detector. 12 dB of signal-to-noise ratio of the shot noise to the electric noise
is obtained with 5 mW of a continuous-wave local oscillator. We analyze the
frequency response and the noise characteristics of a resonant photodetector, and
the theoretical model agrees with the shot noise measurement.
PMID- 29960559
TI - A new experimental capability for the study of regolith surface physical
properties to support science, space exploration, and in situ resource
utilization (ISRU).
AB - Many surfaces found on the Moon, asteroids, Mars, moons, and other planetary
bodies are covered in a fine granular material known as regolith. Increased
knowledge of the physical properties of extraterrestrial regolith surfaces will
help advance the scientific knowledge of these bodies as well as the development
of exploration (e.g., instrument and robotic) and in situ resource utilization
(ISRU) systems. The Center for Space Resources at the Colorado School of Mines as
part of the Institute for Modeling Plasma, Atmospheres, and Cosmic Dust of NASA's
Solar System Exploration Research Virtual Institute has developed a novel system,
called the ISRU Experimental Probe (IEP) that can support studies of dry and icy
regolith from -196 to 150 degrees C and pressure from laboratory ambient
pressure to 10-7 Torr. The IEP system and proof-of-concept results are presented
in this paper.
PMID- 29960560
TI - Ultrafast two-dimensional lithium beam emission spectroscopy diagnostic on the
EAST tokamak.
AB - A diagnostic instrument is described for the Experimental Advanced
Superconducting Tokamak (EAST) for the measurement of the edge plasma electron
density profile and plasma turbulence properties. An accelerated neutral lithium
beam is injected into the tokamak and the Doppler shifted 670.8 nm light emission
of the Li2p-2s transition is detected. A novel compact setup is used, where the
beam injection and observation take place from the same equatorial diagnostic
port and radial-poloidal resolution is achieved with microsecond time resolution.
The observation direction is optimized in order to achieve a sufficient Doppler
shift of the beam light to be able to separate from the strong edge lithium line
emission on this lithium coated device. A 250 kHz beam chopping technique is also
demonstrated for the removal of background light. First results show the
capability of measuring turbulence and its poloidal flow velocity in the scrape
off layer and edge region and the resolution of details of transient phenomena
like edge localized modes with few microsecond time resolution.
PMID- 29960562
TI - High speed CMOS acquisition system based on FPGA embedded image processing for
electro-optical measurements.
AB - Electro-optical measurements, i.e., optical waveguides and plasmonic based
electrochemical impedance spectroscopy (P-EIS), are based on the sensitive
dependence of refractive index of electro-optical sensors on surface charge
density, modulated by an AC electrical field applied to the sensor surface.
Recently, P-EIS has emerged as a new analytical tool that can resolve local
impedance with high, optical spatial resolution, without using microelectrodes.
This study describes a high speed image acquisition and processing system for
electro-optical measurements, based on a high speed complementary metal-oxide
semiconductor (CMOS) sensor and a field-programmable gate array (FPGA) board. The
FPGA is used to configure CMOS parameters, as well as to receive and locally
process the acquired images by performing Fourier analysis for each pixel,
deriving the real and imaginary parts of the Fourier coefficients for the AC
field frequencies. An AC field generator, for single or multi-sine signals, is
synchronized with the high speed acquisition system for phase measurements. The
system was successfully used for real-time angle-resolved electro-plasmonic
measurements from 30 Hz up to 10 kHz, providing results consistent to ones
obtained by a conventional electrical impedance approach. The system was able to
detect amplitude variations with a relative variation of +/-1%, even for rather
low sampling rates per period (i.e., 8 samples per period). The PC (personal
computer) acquisition and control software allows synchronized acquisition for
multiple FPGA boards, making it also suitable for simultaneous angle-resolved P
EIS imaging.
PMID- 29960563
TI - ANITA-An active vibration cancellation system for scanning probe microscopy.
AB - The high sensitivity of scanning probe microscopes poses a barrier to their use
in noisy environments. Vibrational noise, whether from structural or acoustic
sources, can manifest as relative motion between the probe tip and sample, which
then appears in the probe position ("Z") feedback as it tries to cancel this
motion. Here we describe an active cancellation process that nullifies the
appearance of this vibration by adding a drive signal into the existing Z
feedback loop. The drive is digitally calculated from accelerometer-based
vibration measurements. By transferring the vibration cancellation effort to this
drive signal, vibration-created noise is significantly reduced. This inexpensive
and easy solution requires no major instrumental modifications and is ideal for
those looking to place their microscopes in noisier environments, coupled, for
example, to active refrigeration systems (e.g., pulse tube cryocoolers) or other
high-vibration instruments.
PMID- 29960564
TI - Coherent synchrotron radiation monitor for microbunching instability in XFEL.
AB - The microbunching instability is an important issue in an X-ray Free Electron
Laser (XFEL). The intensity of the Free Electron Laser (FEL) can be reduced
significantly by the microbunching instability so that the laser heater is widely
used to reduce it. In the X-ray Free Electron Laser of the Pohang Accelerator
Laboratory (PAL-XFEL), to directly monitor the microbunching instability, a
visible charge coupled device camera was included into the coherent radiation
monitor which uses a pyroelectric detector. It enabled us to measure the
microbunching instability more clearly and optimize the FEL lasing in the PAL
XFEL.
PMID- 29960565
TI - Readout models for BaFBr0.85I0.15:Eu image plates.
AB - The linearity of the photostimulated luminescence process makes repeated image
plate scanning a viable technique to extract a more dynamic range. In order to
obtain a response estimate, two semi-empirical models for the readout fading of
an image plate are introduced; they relate the depth distribution of activated
photostimulated luminescence centers within an image plate to the recorded
signal. Model parameters are estimated from image-plate scan series with BAS-MS
image plates and the Typhoon FLA 7000 scanner for the hard x-ray image-plate
diagnostic over a collection of experiments providing x-ray energy spectra whose
approximate shape is a double exponential.
PMID- 29960566
TI - Hexapod Hall scanner for high-resolution large area magnetic imaging.
AB - We demonstrate a six-axis scanning imaging apparatus using piezo bending
actuators with a large scan range. The six axes of motion of the bending
actuators together with the coupling mechanism to the translation stage allow
complete control of the sensor position and orientation over the scanning
surface, which is ideal for the use of planar sensors such as Hall devices. In
particular, the design allows for in situ correction of the probe tilt angle so
that the sensor distance to sample surface can be minimized. We investigate the
impact of this alignment on the quality of the measured data using an InSb Hall
sensor and a magnetic sample. We also demonstrate a synchronous commutation setup
that can greatly enhance the magnetic image by reducing the Hall signal offset.
PMID- 29960567
TI - Note: Effect of the parasitic forced vibration in an atom gravimeter.
AB - The vibration isolator usually plays an important role in atom interferometry
gravimeters to improve their sensitivity. We show that the parasitic forced
vibration of the Raman mirror, which is induced by external forces acting on the
vibration isolator, can cause a bias in atom gravimeters. The mechanism of how
this effect induces an additional phase shift in our interferometer is analyzed.
Moreover, modulation experiments are performed to measure the dominant part of
this effect, which is caused by the magnetic force between the passive vibration
isolator and the coil of the magneto-optic trap. In our current apparatus, this
forced vibration contributes a systematic error of -2.3(2) * 10-7 m/s2 when the
vibration isolator works in the passive isolation mode. Even suppressed with an
active vibration isolator, this effect can still contribute -6(1) * 10-8 m/s2;
thus, it should be carefully considered in precision atom gravimeters.
PMID- 29960568
TI - Measurement of doping profiles by a contactless method of IR reflectance under
grazing incidence.
AB - An improved contactless method of the measurement and evaluation of charge
carrier profiles in polished wafers by infrared reflectance was developed. The
sensitivity of optical reflectance to the incidence angle was theoretically
analyzed. A grazing incident angle enhances sensitivity to doping profile
parameters. At the same time, the sensitivity to experimental errors sharply
increases around the Brewster angle. Therefore, the optimal angle of 65 degrees
was chosen. Experimental errors such as unintentional polarization of the
measurement beam were minimized by division by reference spectra taken on an
undoped sample and further by normalization to a fixed value in the region of
4000 cm-1 to 7000 cm-1. The carrier profile in boron-doped samples was
parametrized by 3 parameters and that in phosphorous-doped samples was
parametrized by 4 parameters, using additional empirically determined
assumptions. As a physical model, the Drude equation is used with two parameters
assumed to be concentration-dependent: relaxation time and contribution from band
to-band excitations. The model parameters were calibrated independently by
infrared ellipsometry. The presented method gives results in satisfactory
agreement with the profiles measured by the electrochemical capacitance-voltage
method.
PMID- 29960569
TI - Photon Doppler velocimetry measurements of transverse surface velocities.
AB - The goal of this work was to develop a technique for making transverse surface
velocity measures utilizing Photon Doppler Velocimetry (PDV). Such a task is
achieved by transmitting light and collecting Doppler-shifted light at an angle
relative to the normal axis, where measured velocities are representative of a
component of the transverse velocity. Because surface characteristics have an
intrinsic effect on light scatter, different surface preparations were explored
to direct reflectivity, including diffusion by means of sandpapering, or
increasing retroreflectivity by coating with microspheres, milling v-cuts, and
electrochemically etching grooves. Testing of these surface preparations was
performed using an experiment featuring a 30 mm diameter aluminum disk rotating
at 6000 or 6600 RPM. A single PDV collimator was positioned along the rotational
axis of the disk at various angles, resolving the apparent transverse velocity.
To characterize surface preparations, light return and velocities were recorded
as a function of probe angle ranging from 0 degrees to 51 degrees from the
surface normal for each preparation. Polished and electrochemically etched
surfaces did not provide enough reflected light to resolve a beat frequency;
however, sandpapered surfaces, retroreflective microspheres, and milled v-cuts
provided adequate reflected light for incidence angles up to 51 degrees .
Applications of the surface preparations were then studied in gas gun
experiments. Retroreflective microspheres were studied in a planar impact
experiment, and milled v-cuts were studied in an oblique impact experiment. A
normal and transverse profile of particle velocity was resolved in the oblique
impact experiment.
PMID- 29960570
TI - Erratum: "Invited Review Article: 'Hands-on' laser-driven ion acceleration: A
primer for laser-driven source development and potential applications" [Rev. Sci.
Instrum. 87, 071101 (2016)].
PMID- 29960571
TI - Singular value decomposition based impulsive noise reduction in multi-frequency
phase-sensitive demodulation of electrical impedance tomography.
AB - As an important means in electrical impedance tomography (EIT), multi-frequency
phase-sensitive demodulation (PSD) can be viewed as a matched filter for
measurement signals and as an optimal linear filter in the case of Gaussian-type
noise. However, the additive noise usually possesses impulsive noise
characteristics, so it is a challenging task to reduce the impulsive noise in
multi-frequency PSD effectively. In this paper, an approach for impulsive noise
reduction in multi-frequency PSD of EIT is presented. Instead of linear filters,
a singular value decomposition filter is employed as the pre-stage filtering
module prior to PSD, which has advantages of zero phase shift, little distortion,
and a high signal-to-noise ratio (SNR) in digital signal processing. Simulation
and experimental results demonstrated that the proposed method can effectively
eliminate the influence of impulsive noise in multi-frequency PSD, and it was
capable of achieving a higher SNR and smaller demodulation error.
PMID- 29960572
TI - Design and validation of an advanced entrained flow reactor system for studies of
rapid solid biomass fuel particle conversion and ash formation reactions.
AB - The design and validation of a newly commissioned entrained flow reactor is
described in the present paper. The reactor was designed for advanced studies of
fuel conversion and ash formation in powder flames, and the capabilities of the
reactor were experimentally validated using two different solid biomass fuels.
The drop tube geometry was equipped with a flat flame burner to heat and support
the powder flame, optical access ports, a particle image velocimetry (PIV) system
for in situ conversion monitoring, and probes for extraction of gases and
particulate matter. A detailed description of the system is provided based on
simulations and measurements, establishing the detailed temperature distribution
and gas flow profiles. Mass balance closures of approximately 98% were achieved
by combining gas analysis and particle extraction. Biomass fuel particles were
successfully tracked using shadow imaging PIV, and the resulting data were used
to determine the size, shape, velocity, and residence time of converting
particles. Successful extractive sampling of coarse and fine particles during
combustion while retaining their morphology was demonstrated, and it opens up for
detailed time resolved studies of rapid ash transformation reactions; in the
validation experiments, clear and systematic fractionation trends for K, Cl, S,
and Si were observed for the two fuels tested. The combination of in situ access,
accurate residence time estimations, and precise particle sampling for subsequent
chemical analysis allows for a wide range of future studies, with implications
and possibilities discussed in the paper.
PMID- 29960573
TI - On the scattering correction of fast-ion D-alpha signals on NSTX-U.
AB - Analysis of fast-ion D-alpha (FIDA) data on National Spherical Torus Experiment
Upgrade (NSTX-U) shows that the cold Dalpha line contaminates the FIDA baseline.
The scattered light is comparable to the FIDA emission. A scattering correction
is required to extract the FIDA signal. Two methods that relate the scattered
light contamination to the intensity of the cold Dalpha line are employed. One
method uses laboratory measurements with a calibration lamp; the other method
uses data acquired during plasma operation and singular value decomposition
analysis. After correction, both the FIDA spectra and spatial profile are in
better agreement with theoretical predictions.
PMID- 29960574
TI - Polarimetric microscopy for optical control and high precision measurement of
valley polarization.
AB - Two-dimensional transition metal dichalcogenides (2D TMDCs) have two degenerate
energy valleys in their Brillouin zone, and these two separate valleys can be
used as an information carrier in optoelectronic devices. Circularly polarized
optical pumping can selectively populate a single valley, resulting in direct
band transitions at the populated valley and associated circularly polarized
photoluminescence (PL) emission. However, the birefringence and linear dichroism
in optical microscopes can not only distort the circular polarization states of
optical pumping but also contaminate experimentally derived information about the
polarization states of valley-polarized PL signals. To solve this problem, we
suggest a polarimetric microscopy method that manipulates the valley population
by optical pumping and measures the polarized PL emission of 2D TMDCs; pumping
beam polarization can be precisely controlled by the polarization correction
unit, and the original polarization state of the emitted PL signal can be
recovered using the Mueller matrix inherent to the optical experimental setup.
Using our method, errors when measuring the degree of circular polarization in PL
signals can be reduced from 19% to 6%, enabling accurate estimation of exciton
lifetimes. Our result offers an accurate and reliable way to process information
in valley-based optoelectronic devices.
PMID- 29960575
TI - The high-energy x-ray diffraction and scattering beamline at the Canadian Light
Source.
AB - The optical design for the high-energy x-ray diffraction and scattering beamline
of the Brockhouse sector at the Canadian Light Source is described. The design is
based on a single side-bounce silicon focusing monochromator that steers the
central part of a high-field permanent magnet wiggler beam into the experimental
station. Two different configurations are proposed: a higher energy resolution
with vertical focusing and a lower energy resolution with horizontal and vertical
focusing. The monochromator will have the possibility of mounting three crystals:
one crystal optimized for 35 keV that focuses in the horizontal and vertical
directions using reflection (1,1,1) and two other crystals both covering the
energies above 40 keV: one with only vertical focusing and another one with
horizontal and vertical focusing. The geometry of the last two monochromator
crystals was optimized to use reflections (4,2,2) and (5,3,3) to cover the broad
energy range from 40 to 95 keV.
PMID- 29960576
TI - Two-dimensional displacement measurement based on two parallel gratings.
AB - In this paper, a two-dimensional (2-D) planar encoder based on two parallel
gratings, which includes a scanning grating and scale grating, is presented. The
scanning grating is a combined transmission rectangular grating comprised of a 2
D grating located at the center and two one-dimensional (1-D) gratings located at
the sides. The grating lines of the two 1-D gratings are perpendicular to each
other and parallel with the 2-D grating lines. The scale grating is a 2-D
reflective-type rectangular grating placed in parallel with the scanning grating,
and there is an angular difference of 45 degrees between the grating lines of
the two 2-D gratings. With the special structural design of the scanning grating,
the encoder can measure the 2-D displacement in the grating plane simultaneously,
and the measured interference signals in the two directions are uncoupled.
Moreover, by utilizing the scanning grating to modulate the phase of the
interference signals instead of the prisms, the structure of the encoder is
compact. Experiments were implemented, and the results demonstrate the validity
of the 2-D planar grating encoder.
PMID- 29960577
TI - The software-defined fast post-processing for GEM soft x-ray diagnostics in the
Tungsten Environment in Steady-state Tokamak thermal fusion reactor.
AB - This article presents a novel software-defined server-based solutions that were
introduced in the fast, real-time computation systems for soft X-ray diagnostics
for the WEST (Tungsten Environment in Steady-state Tokamak) reactor in Cadarache,
France. The objective of the research was to provide a fast processing of data at
high throughput and with low latencies for investigating the interplay between
the particle transport and magnetohydrodynamic activity. The long-term objective
is to implement in the future a fast feedback signal in the reactor control
mechanisms to sustain the fusion reaction. The implemented electronic measurement
device is anticipated to be deployed in the WEST. A standalone software-defined
computation engine was designed to handle data collected at high rates in the
server back-end of the system. Signals are obtained from the front-end field
programmable gate array mezzanine cards that acquire and perform a selection from
the gas electron multiplier detector. A fast, authorial library for plasma
diagnostics was written in C++. It originated from reference offline MATLAB
implementations. They were redesigned for runtime analysis during the experiment
in the novel online modes of operation. The implementation allowed the
benchmarking, evaluation, and optimization of plasma processing algorithms with
the possibility to check the consistency with reference computations written in
MATLAB. The back-end software and hardware architecture are presented with data
evaluation mechanisms. The online modes of operation for the WEST are discussed.
The results concerning the performance of the processing and the introduced
functionality are presented.
PMID- 29960578
TI - Feedback control of local hotspot temperature using resistive on-substrate
nanoheater/thermometer.
AB - This article reports the active control of a local hotspot temperature for
accurate nanoscale thermal transport measurement. To this end, we have fabricated
resistive on-substrate nanoheater/thermometer (NH/T) devices that have a sensing
area of ~350 nm * 300 nm. Feedback-controlled temporal heating and cooling
experiments of the NH/T device confirm that the feedback integral gain plays a
dominant role in device's response time for various setpoint temperatures. To
further verify the integration of the feedback controller with the NH/T devices,
a local tip-induced cooling experiment is performed by scanning a silicon tip
over the hotspot area in an atomic force microscope platform. By carefully
optimizing the feedback gain and the tip scan speed, we can control the hotspot
temperature with the accuracy of ~+/-1 K for a broad range of setpoints from 325
K to 355 K. The obtained tip-substrate thermal conductance, including the effects
of solid-solid conduction, water meniscus, air conduction, and near-field thermal
radiation, is found to be a slightly increasing function of temperature in the
range of 127 +/- 25 to 179 +/- 16 nW/K. Our work demonstrates the reliable
controllability of a local hotspot temperature, which will allow the further
improvement of various nanoscale thermal metrologies including scanning thermal
microscopy and nanoscale thermometry.
PMID- 29960579
TI - Note: Optics design of a periscope for the KSTAR visible inspection system with
mitigated neutron damages on the camera.
AB - The visible TV system used in the Korea Superconducting Tokamak Advanced Research
device has been equipped with a periscope to minimize the damage on its CCD
pixels from neutron radiation. The periscope with more than 2.3 m in overall
length has been designed for the visible camera system with its semi-diagonal
field of view as wide as 30 degrees and its effective focal length as short as
5.57 mm. The design performance of the periscope includes the modulation transfer
function greater than 0.25 at 68 cycles/mm with low distortion. The installed
periscope system has confirmed the image qualities as designed and also as
comparable as those from its predecessor but with far less probabilities of
neutral damages on the camera.
PMID- 29960580
TI - A flow-pulse adsorption-microcalorimetry system for studies of adsorption
processes on powder catalysts.
AB - A pulse chemisorption system combining a Tian-Calvet microcalorimeter (Setaram
Sensys EVO 600) and an automated chemisorption apparatus (Micromeritics Autochem
II 2920) was established to accurately measure differential adsorption heats of
gas molecules' chemisorption on solid surfaces in a flow-pulse mode. Owing to
high sensitivity and high degree of automation in a wide range of temperatures
from -100 to 600 degrees C, this coupled system can present adsorption heats as
a function of adsorption temperature and adsorbate coverage. The functions of
this system were demonstrated by successful measurements of CO adsorption heats
on Pd surfaces at various temperatures and also at different CO coverages by
varying the CO concentration in the pulse dose. Key parameters, including
adsorption amounts, integral adsorption heats, and differential adsorption heats
of CO adsorption on a Pd/CeO2 catalyst, were acquired. Our adsorption
microcalorimetry system provides a powerful technique for the investigation of
adsorption processes on powder catalysts.
PMID- 29960581
TI - Integration of fiber Bragg grating temperature sensors in plasma facing
components of the WEST tokamak.
AB - Plasma Facing Components (PFC) temperature measurement is mandatory to ensure
safe high power and long pulse tokamak operation. IR thermography systems which
are widely used in magnetic fusions devices become challenged with the choice of
tungsten as a PFC material in the ITER tokamak, mainly due to emissivity
uncertainties and reflection issues in a hot environment. Embedded temperature
measurements are foreseen to cross-check the IR thermography measurements. Fiber
Bragg grating sensors are potentially of great interest for this application
because they are immune to electromagnetic interference and allow the measurement
of a large number of temperature spots on a single fiber. Four optical fiber
temperature sensing probes, each of them including 11 regenerated fiber Bragg
gratings equally spaced by 12.5 mm (equivalent to one ITER-like tungsten
monoblock), have been specifically designed and manufactured for the WEST project
(W-tungsten Environment and Steady State Tokamak). The four probes are embedded
in W-coated graphite components at two different distances from the surface, 3.5
mm and 7 mm, to cover a wide range of temperatures up to 900 degrees C. This
paper addresses the design and integration issues and the qualification and
performance assessment performed in the laboratory. It also shows the first
measurements of this new diagnostic achieved in a tokamak environment during
baking of the machine and during early diverted plasma exposure.
PMID- 29960582
TI - A new three-dimensional nonscanning laser imaging system based on the
illumination pattern of a point-light-source array.
AB - One of the most important goals of research on three-dimensional nonscanning
laser imaging systems is the improvement of the illumination system. In this
paper, a new three-dimensional nonscanning laser imaging system based on the
illumination pattern of a point-light-source array is proposed. This array is
obtained using a fiber array connected to a laser array with each unit laser
having independent control circuits. This system uses a point-to-point imaging
process, which is realized using the exact corresponding optical relationship
between the point-light-source array and a linear-mode avalanche photodiode array
detector. The complete working process of this system is explained in detail, and
the mathematical model of this system containing four equations is established. A
simulated contrast experiment and two real contrast experiments which use the
simplified setup without a laser array are performed. The final results
demonstrate that unlike a conventional three-dimensional nonscanning laser
imaging system, the proposed system meets all the requirements of an eligible
illumination system. Finally, the imaging performance of this system is analyzed
under defocusing situations, and analytical results show that the system has good
defocusing robustness and can be easily adjusted in real applications.
PMID- 29960583
TI - Laser driving and data processing concept for mobile trace gas sensing: Design
and implementation.
AB - High precision mobile sensing of multi-species gases is greatly demanded in a
wide range of applications. Although quantum cascade laser absorption
spectroscopy demonstrates excellent field-deployment capabilities for gas
sensing, the implementation of this measurement technique into sensor-like
portable instrumentation still remains challenging. In this paper, two crucial
elements, the laser driving and data acquisition electronics, are addressed.
Therefore, we exploit the benefits of the time-division multiplexed intermittent
continuous wave driving concept and the real-time signal pre-processing
capabilities of a commercial System-on-Chip (SoC, Red Pitaya). We describe a re
designed current driver that offers a universal solution for operating a wide
range of multi-wavelength quantum cascade laser device types and allows stacking
for the purpose of multiple laser configurations. Its adaptation to the various
driving situations is enabled by numerous field programmable gate array (FPGA)
functionalities that were developed on the SoC, such as flexible generation of a
large variety of synchronized trigger signals and digital inputs/outputs (DIOs).
The same SoC is used to sample the spectroscopic signal at rates up to 125 MS/s
with 14-bit resolution. Additional FPGA functionalities were implemented to
enable on-board averaging of consecutive spectral scans in real-time, resulting
in optimized memory bandwidth and hardware resource utilisation and autonomous
system operation. Thus, we demonstrate how a cost-effective, compact, and
commercial SoC can successfully be adapted to obtain a fully operational research
grade laser spectrometer. The overall system performance was examined in a
spectroscopic setup by analyzing low pressure absorption features of CO2 at 4.3
MUm.
PMID- 29960585
TI - Colorectal cancer and screening awareness and sources of information in the
Hungarian population.
AB - BACKGROUND: This study aims to survey the level of awareness of colorectal cancer
and screening and to identify sources of information among the population under
investigation. METHODS: A cross-sectional study was conducted among 1150 adults
between the ages of 40 and 70 using quota sampling. Data were collected through
self-made questionnaires to be completed by respondents. RESULTS: 32.7% of the
participants correctly identified the recommended beginning of colorectal cancer
screening, these participants were more likely to see their physician more
frequently in the past years than those answering to the qusetion incorrectly (p
= 0.008). 22.4% of the respondents were in possession of appropriate information
on the frequency of colorectal cancer screening and had a relatively high level
of educational attainment (p < 0.001). Very few respondents were well-informed
about the risk factors and symptoms of colorectal cancer. Those who were well
informed were likely to live in a county town (p < 0.001) and to have a
relatively high level of educational attainment (p < 0.001). They were most
likely to have accessed their information on the internet. 27.0% of respondents
had not heard of CRC screening methods before. They were likely to be male and
relatively young and to have a relatively low level of educational attainment.
Furthermore, they saw their doctor relatively seldom. The respondents who had
heard about screening methods were most likely to have gathered their information
from health workers. CONCLUSIONS: The majority of respondents did not have
sufficient information about colorectal cancer and screening. This is
particularly true of less educated, younger male participants who do not live in
a county town and of respondents who see their physician relatively seldom.
Sources of information should be used more effectively, thus yielding an
increased level of awareness.
PMID- 29960586
TI - Jaw tremor: a manifestation of vascular parkinsonism? - a case report.
AB - BACKGROUND: Vascular Parkinsonism (VP) is a heterogeneous group of conditions
that manifest clinically in parkinsonian features, but are presumably of vascular
cause. It is usually bilateral, non-tremulous, and frequently associated with
pyramidal signs. Classically VP is described as lower body parkinsonism affecting
predominantly the legs. CASE PRESENTATION: A 67 years old lady presented with a
history of acute onset jaw tremor, with tremor predominantly in both upper limbs.
Neurological examination revealed hypomimia of the face with cogwheel rigidity
and bradykinesia bilaterally, predominantly in the upper limbs without pyramidal
signs. She had a marked tremor of the jaw at rest. When she was asked to open her
mouth the tremor was re-emergent. Non contrast CT scan of her brain revealed an
infarction in the region of putamen on the left with no evidence of diffuse
subcortical white matter ischemia or extension to the caudate nucleus. She was
treated with levodopa and responded well to medication. CONCLUSIONS: This case
describes atypical clinical features which could be associated with VP including
jaw tremor. This case also stresses the importance of initiating a trial of
levodopa as certain patients may respond well to medication.
PMID- 29960584
TI - Actions of metformin and statins on lipid and glucose metabolism and possible
benefit of combination therapy.
AB - Patients with diabetes type 2 have an increased risk for cardiovascular disease
and commonly use combination therapy consisting of the anti-diabetic drug
metformin and a cholesterol-lowering statin. However, both drugs act on glucose
and lipid metabolism which could lead to adverse effects when used in combination
as compared to monotherapy. In this review, the proposed molecular mechanisms of
action of statin and metformin therapy in patients with diabetes and dyslipidemia
are critically assessed, and a hypothesis for mechanisms underlying interactions
between these drugs in combination therapy is developed.
PMID- 29960587
TI - Interactions between ALDH2 rs671 polymorphism and lifestyle behaviors on coronary
artery disease risk in a Chinese Han population with dyslipidemia: A guide to
targeted heart health management.
AB - BACKGROUND: Both aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and
lifestyle behaviors are involved in coronary artery disease (CAD), while the
interaction between them is currently unknown. METHODS: A nested case-control
study was conducted in 161 patients with CAD and 495 controls in dyslipidemia
population in Yinzhou District, Ningbo, Zhejiang Province, China, in August 2013.
Anthropometric data and blood samples were collected, demographic characteristics
and lifestyle behaviors information were obtained by a face-to-face interview,
dietary intake was assessed by a food frequency questionnaire, and genomic DNA
was genotyped. RESULTS: Carriers with increasing number of A alleles had an
elevated CAD risk compared with G allele carriers (adjusted OR = 1.483, 95% CI =
1.114-1.974). Carriers of rs671 A/G and A/A genotypes had a higher CAD risk than
carriers of G/G genotype (adjusted OR = 1.492, 95% CI = 1.036-2.148). Similarly,
individuals with rs671 A/A genotype had a higher CAD risk than individuals with
A/G and G/G genotypes (adjusted OR = 2.161, 95% CI = 1.139-4.101). We found a
borderline additive interaction between regular fried food intake and A/A and A/G
genotypes, and a significantly additive interaction between sedentary/light
physical activity and A/A and A/G genotypes. CONCLUSIONS: Individuals with A/A or
A/G genotypes of rs671 have a higher CAD risk, if they lack physical activity and
take fried food regularly, than individuals with G/G genotypes. These findings
can help to provide a guide to targeted heart health management.
PMID- 29960588
TI - Association between epicardial adipose tissue, high-sensitivity C-reactive
protein and myocardial dysfunction in middle-aged men with suspected metabolic
syndrome.
AB - BACKGROUND: As body fat composition and metabolism differ between men and women,
we evaluated sex-related differences in the association among epicardial adipose
tissue (EAT), secretome profile, and myocardial function of subjects with
suspected metabolic syndrome. METHODS: We evaluated 277 participants (men, n =
140; 56.1 +/- 4.7 years) who underwent conventional echocardiography and two
dimensional speckle tracking from the Seoul Metabolic Syndrome cohort. EAT was
measured from the right ventricular free wall perpendicular to the aortic annulus
at end systole. Global longitudinal strain (GLS) was obtained from 18 apical
segments. Apolipoprotein A1, apolipoprotein B, adiponectin, and high-sensitivity
C-reactive protein (hs-CRP) levels were measured using immunoturbidimetry assay.
RESULTS: Mean age, body mass index, and hs-CRP level did not differ by sex. Waist
circumference, fasting blood glucose level, and triglyceride/high-density
lipoprotein cholesterol ratio were higher, and apolipoprotein AI and adiponectin
levels were lower in men. No significant difference in mean EAT thickness was
found (7.02 +/- 1.81 vs. 7.13 +/- 1.70 mm, p = 0.613). Men had a higher left
ventricular (LV) mass index and lower GLS. EAT thickness was associated with hs
CRP level in men alone (beta = 0.206, p = 0.015). LV mass index (beta = 2.311, p
= 0.037) and function represented by e' (beta = - 0.279, p = 0.001) and GLS (beta
= - 0.332, p < 0.001) were independently associated with EAT thickness in men
alone. CONCLUSIONS: In middle-aged subjects with suspected metabolic syndrome,
EAT was associated with inflammation represented by hs-CRP level, LV mass, and
subclinical myocardial dysfunction only in men, suggesting that the inflammatory
activity of EAT induced myocardial remodeling and dysfunction in middle-aged
subjects but was attenuated in women. Trial registration NCT02077530 (date of
registration: November 1, 2013).
PMID- 29960589
TI - The course of complaints of arm, neck and/or shoulder: a cohort study in a
university population participating in work or study.
AB - BACKGROUND: Not much is known about the characteristics, course and prognosis of
complaints of arm, neck and/or shoulder that have not been caused by a trauma or
systemic disease (CANS), in a screened population. This study aims to: (1)
describe personal and complaint characteristics in a screened population; (2)
describe the course during one-year follow-up, in terms of the three different
domains of functioning of the International Classification of Functioning,
Disability and Health (ICF); and (3) to explore prognostic factors for the
different domains of functioning at one-year follow-up. Additionally, this study
aims to investigate the manifestation of selection effects (i.e. tertiary
selection effects), in order to understand their impact on the interpretation of
results. METHODS: A cross-sectional survey was conducted in a university
population. Survey respondents who fulfilled eligibility criteria were asked to
participate in a longitudinal cohort study. The course of CANS was assessed in
terms of the three ICF domains of functioning. Possible prognostic factors across
the different components of the ICF were selected to investigate their influence
on outcome at one-year follow-up. Non-response analyses were performed to
investigate the presence of tertiary selection effects. RESULTS: The results
revealed a population with relatively mild complaints at baseline, and a
relatively stable course during follow-up. Because of the small change in scores
between baseline and follow-up measurements, examination of prognostic factors
was not feasible. The results of the non-response analyses revealed some
indications for the potential presence of tertiary selection effects, which may
imply that the results obtained are a slight overestimation of the true results.
CONCLUSION: The results of this study demonstrate mild complaints at baseline and
an overall stable course during one-year follow-up. Since selection effects
cannot be ruled out, the true course might possibly be somewhat less favourable
than our results suggest.
PMID- 29960590
TI - Patient safety and safety culture in primary health care: a systematic review.
AB - BACKGROUND: Patient safety in primary care is an emerging field of research with
a growing evidence base in western countries but little has been explored in the
Gulf Cooperation Council Countries (GCC) including the Sultanate of Oman. This
study aimed to review the literature on the safety culture and patient safety
measures used globally to inform the development of safety culture among health
care workers in primary care with a particular focus on the Middle East. METHODS:
A systematic review of the literature. Searches were undertaken using Medline,
EMBASE, CINAHL and Scopus from the year 2000 to 2014. Terms defining safety
culture were combined with terms identifying patient safety and primary care.
RESULTS: The database searches identified 3072 papers that were screened for
inclusion in the review. After the screening and verification, data were
extracted from 28 papers that described safety culture in primary care. The
global distribution of the articles is as follows: the Netherlands (7), the
United States (5), Germany (4), the United Kingdom (1), Australia, Canada and
Brazil (two for each country), and with one each from Turkey, Iran, Saudi Arabia
and Kuwait. The characteristics of the included studies were grouped under the
following themes: safety culture in primary care, incident reporting, safety
climate and adverse events. The most common theme from 2011 onwards was the
assessment of safety culture in primary care (13 studies, 46%). The most commonly
used safety culture assessment tool is the Hospital survey on patient safety
culture (HSOPSC) which has been used in developing countries in the Middle East.
CONCLUSIONS: This systematic review reveals that the most important first step is
the assessment of safety culture in primary care which will provide a basic
understanding to safety-related perceptions of health care providers. The HSOPSC
has been commonly used in Kuwait, Turkey, and Iran.
PMID- 29960591
TI - Prognostic impact of HbA1c variability on long-term outcomes in patients with
heart failure and type 2 diabetes mellitus.
AB - BACKGROUND: The prognostic impact of long-term glycemic variability on clinical
outcomes in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM)
remains unclear. We determined and compared hemoglobin A1c (HbA1c) variability
and clinical outcomes for patients with HF with preserved ejection fraction
(HFpEF), HF with mid-range ejection fraction (HFmrEF) and HF with reduced
ejection fraction (HFrEF) in a prospective longitudinal study. METHODS: Patients
with HF and T2DM, undergone 3 or more HbA1c determinations during the first 18
months, were then followed for 42 months. The primary outcome was death from any
cause. Secondary outcome was composite endpoints with death and HF
hospitalization. Cox proportional hazards models were used to compare outcomes
for patients with HFpEF, HFmrEF and HFrEF. RESULTS: Of 902 patients enrolled,
32.2% had HFpEF, 14.5% HFmrEF, and 53.3% HFrEF. During 42 months of follow-up,
270 (29.9%) patients died and 545 (60.4%) patients experienced composite
endpoints of death and HF readmission. The risk of all-cause death or composite
endpoints was lower for HFpEF than HFrEF. Moreover, higher HbA1c variability was
associated with higher all-cause mortality or composite endpoints and HbA1c
variability was an independent predictor of all-cause mortality or composite
endpoints, regardless of EF. CONCLUSIONS: This prospective longitudinal study
showed that the all-cause death and composite events was lower for HFpEF than
HFrEF. HbA1c variability was independently and similarly predictive of death or
combined endpoints in the three HF phenotypes.
PMID- 29960592
TI - Late recurrence of pStage 1 low-grade serous ovarian tumor presenting as a
symptomatic bone metastasis: a case report.
AB - BACKGROUND: Ovarian serous borderline tumor/atypical proliferative serous tumor
(SBT/APST) is characterized by presenting at an early stage and much longer
survival than high-grade serous carcinoma. Given that the prognosis of ovarian
SBT/APST with no invasive features is excellent, remote relapse after surgery can
pose a diagnostic pitfall. Bone metastasis as transformed low-grade carcinoma is
an extremely rare initial presentation of recurrence in patients whose primary
tumor was confined to the ovaries. CASE PRESENTATION: A 55-year-old Japanese
woman who had undergone surgery for a right ovarian tumor 13 years previously
presented with right-lateral chest pain and neurologic abnormalities in the lower
limbs. Computed tomography (CT) scan and magnetic resonance imaging revealed an
irregular mass in the right arch of the 12th thoracic vertebra, extending through
the intervertebral foramen and into surrounding soft tissue, the maximum diameter
of the whole mass being 78 mm. Pathological examination of a CT-guided needle
biopsy of the paraspinal lesion demonstrated papillary cell clusters with blunt
nuclear atypia and psammomatous calcification that were positive for PAX8,
estrogen receptor, and WT1, but negative for thyroglobulin on immunohistochemical
testing, and of a P53 non-mutational pattern. On clinicopathologic review, the
previous 13- * 11- * 9-cm ovarian tumor was an intracystic and exophytic
papillary growth without surface involvement; it had ruptured intraoperatively.
Microscopically there was serous epithelium with minimal cytologic atypia
proliferating in hierarchical branches with no invasive foci or micropapillary
components. The tumor was confined to the right ovary with no peritoneal
implants. Neither primary nor metastatic tumor harbored KRAS/BRAF mutations
according to polymerase chain reaction using formalin-fixed paraffin-embedded
tissues. We concluded that, after a 13-year disease-free interval, the paraspinal
lesion was bone metastasis of low-grade carcinoma originating from the ovarian
SBT/APST. The patient received radiotherapy for the paraspinal lesion followed by
administration of paclitaxel and carboplatin plus bevacizumab and remains alive
168 months after the initial surgery. CONCLUSIONS: Pathologists and radiologists
should not exclude late recurrence of ovarian SBT/APST when bone metastases are
suspected, even when neither peritoneal nor lymph node involvement are detected.
Long-term surveillance of women with ovarian serous tumors with no invasive
features is recommended.
PMID- 29960593
TI - Optimising treatment in opioid dependency in primary care: results from a
national key stakeholder and expert focus group in Ireland.
AB - BACKGROUND: Treatment for opioid dependence in Ireland is provided predominantly
by general practitioners (GP) who have undergone additional training in opioid
agonist treatment (OAT) and substance misuse. The National Methadone Treatment
Programme (MTP) was introduced in 1998, and was designed to treat the opioid
dependent population and to regulate the prescribing regimes at the time. The
past two decades have seen the increased prescribing of methadone in primary care
and changes in type of opioid abused, in particular, the increased use of over
the counter (OTC) and prescription medications. Despite the scaling up of OAT in
Ireland, drug related deaths however have increased and waiting lists for
treatment exist in some areas outside the capital, Dublin. Two previous MTP
reviews have made recommendations aimed at improving and scaling up of OAT in
Ireland. This study updates these recommendations and is the first time that a
group of national experts have engaged in structured research to identify
barriers to OAT delivery in Ireland. The aim was to explore the views of national
statutory and non-statutory stakeholders and experts on current barriers within
the MTP and broader OAT delivery structures in order to inform their future
design and implementation. METHODS: A single focus group with a chosen group of
national key stakeholders and experts with a broad range of expertise (clinical,
addiction and social inclusion management, harm reduction, homelessness,
specialist GPs, academics) (n = 11) was conducted. The group included national
representation from the areas of drug treatment delivery, service design, policy
and practice in Ireland. RESULTS: Four themes emerged from the narrative
analysis, and centred on OAT Choices and Patient Characteristics; Systemic
Barriers to Optimal OAT Service Provision; GP Training and Registration in the
MTP, and Solutions and Models of Good Practice: Using What You Have. CONCLUSION:
The study identified a series of improvement strategies which could reduce
barriers to access and the stigma associated with OAT, optimise therapeutic
choices, enhance interagency care planning within the MTP, utilise the strengths
of community pharmacy and nurse prescribers, and recruit and support methadone
prescribing GPs in Ireland.
PMID- 29960594
TI - The association of body mass index with difficult tracheal intubation management
by direct laryngoscopy: a meta-analysis.
AB - BACKGROUND: Obesity is a serious disorder and may bring about many difficulties
of perioperative management. A systematic review was conducted to assess the
association between obesity and difficult intubation. METHODS: We searched
electronic databases for related reviews and references of meta-analyses on
August 14, 2017. The databases of PubMed, Embase, and the Cochrane controlled
trials register were searched compared obese with non-obese patients in which
difficult intubation rate of the adult population were retrieved. Patients with a
BMI >= 30 kg.m- 2 were considered obese. The primary outcome was difficult
tracheal intubation; secondary outcomes were the rates of difficult laryngoscopy
and Mallampati score >= 3. This review included papers published from 1998 to
2015. RESULTS: This review included 204,303 participants in 16 studies. There was
a statistically significant association between obesity and risk of difficult
tracheal intubation (pooled RR = 2.04, 95% CI: 1.16-3.59, p = 0.01; I2 = 71%, p =
0.008, Power = 1.0). It also showed significantly association between obesity and
risk of difficult laryngoscopy (pooled RR = 1.54, 95% CI: 1.25-1.89, p < 0.0001;
I2 = 45%, p = 0.07, Power = 1.0), obesity and risk of Mallampati score >= 3
(pooled RR = 1.83, 95% CI: 1.24-2.69, p = 0.002; I2 = 81%, p < 0.00001, Power =
0.93). However, there were no association of obesity and risks of difficult
intubation compared with non-obesity in the cohort studies (pooled RR = 3.41, 95%
CI: 0.88-13.23, p = 0.08; I2 = 50%, p = 0.14) and the elective tracheal
intubation (pooled RR = 2.31, 95% CI: 0.76-6.99, p = 0.14; I2 = 73%, p = 0.01),
no associated with an increased risk of difficult laryngoscopy in the sniffing
position (pooled RR = 2.00, 95% CI: 0.97-4.15, p = 0.06; I2 = 67%, p = 0.03).
CONCLUSION: Obesity was associated with an increased risk of difficult
intubation, difficult laryngoscopy and Mallampati score >= 3 in adults patients
undergoing general surgical procedures. However, there were no association of
obesity and risks of difficult intubation compared with non-obesity in the cohort
studies and the elective tracheal intubation, no associated with an increased
risk of difficult laryngoscopy in the sniffing position. Future analyses should
explore the association of BMI and difficult airway.
PMID- 29960595
TI - Associations of self-reported physical activity and depression in 10,000 Irish
adults across harmonised datasets: a DEDIPAC-study.
AB - BACKGROUND: Depression is a prevalent, debilitating, and often recurrent mood
disorder for which successful first-line treatments remains limited. The purpose
of this study was to investigate the cross-sectional associations between self
reported physical activity (PA) and depressive symptoms and status among Irish
adults, using two existing datasets, The Irish Longitudinal Study on Ageing
(TILDA) and The Mitchelstown Cohort Study. METHODS: The two selected databases
were pooled (n = 10,122), and relevant variables were harmonized. PA was measured
using the short form International Physical Activity Questionnaire. Depressive
symptoms were measured by the Center for Epidemiologic Studies Depression (CES-D)
questionnaire. Participants were classified as meeting World Health Organization
moderate-to-vigorous PA (MVPA) guidelines or not, and divided into tertiles based
on weekly minutes of MVPA. A CES-D score of >=16 indicated elevated depressive
symptoms. Data collection were conducted in 2010-2011. RESULTS: Significantly
higher depressive symptoms were reported by females (7.11 +/- 7.87) than males
(5.74 +/- 6.86; p < 0.001). Following adjustment for age, sex, BMI, and dataset,
meeting the PA guidelines was associated with 44.7% (95%CI: 35.0 to 52.9; p <
0.001) lower odds of elevated depressive symptoms. Compared to the low PA
tertile, the middle and high PA tertiles were associated with 25.2% (95%CI: 8.7
to 38.6; p < 0.01) and 50.8% (95%CI: 40.7 to 59.2; p < 0.001) lower odds of
elevated depressive symptoms, respectively. CONCLUSION: Meeting the PA guidelines
is associated with lower odds of elevated depressive symptoms, and increased
volumes of MVPA are associated with lower odds of elevated depressive symptoms.
PMID- 29960597
TI - Modifiable dementia risk score to study heterogeneity in treatment effect of a
dementia prevention trial: a post hoc analysis in the preDIVA trial using the
LIBRA index.
AB - BACKGROUND: Selecting high-risk participants for dementia prevention trials based
on a modifiable dementia risk score may be advantageous, as it increases the
opportunity for intervention. We studied whether a multi-domain intervention can
prevent all-cause dementia and cognitive decline in older people across three
different levels of a modifiable dementia risk score. METHODS: Prevention of
Dementia by Intensive Vascular Care (preDIVA) is a randomised controlled trial
studying the effect of multi-domain vascular care during 6-8 years on incident
all-cause dementia in community-dwelling people aged 70-78 years. For this post
hoc analysis, we stratified preDIVA participants in tertiles based on their
baseline LIfestyle for BRAin Health (LIBRA) index, a modifiable dementia risk
score. With Cox proportional hazards regression, the intervention effect on
dementia was assessed. The effect on cognition was measured every 2 years with
the Mini-Mental State Examination and Visual Association Test. RESULTS: Dementia
developed in 220 of 3274 (6.7%) participants. In participants with a low,
intermediate and high LIBRA index, the hazard ratio (HR) of the intervention on
incident dementia was respectively 0.71 (95% CI 0.45-1.12), 1.06 (95% CI 0.66
1.69) and 1.02 (95% CI 0.64-1.62). Also, when adding the non-modifiable risk
factors age, education and sex to the index, results were comparable
(respectively HR 0.88, 95% CI 0.54-1.43; HR 0.91, 95% CI 0.57-1.47; HR 0.92, 95%
CI 0.59-1.41). There was no statistically significant intervention effect on
cognition during follow-up across the LIBRA groups. CONCLUSIONS: In the preDIVA
study population aged 70-78 years, the LIBRA modifiable dementia risk score did
not identify a (high-)risk group in whom the multi-domain intervention was
effective in preventing dementia or cognitive decline. TRIAL REGISTRATION:
International Standard Randomised Controlled Trial Number registry,
ISRCTN29711771 . Registered on 14 February 2006.
PMID- 29960596
TI - Structural aspects of plasticity in the nervous system of Drosophila.
AB - Neurons extend and retract dynamically their neurites during development to form
complex morphologies and to reach out to their appropriate synaptic partners.
Their capacity to undergo structural rearrangements is in part maintained during
adult life when it supports the animal's ability to adapt to a changing
environment or to form lasting memories. Nonetheless, the signals triggering
structural plasticity and the mechanisms that support it are not yet fully
understood at the molecular level. Here, we focus on the nervous system of the
fruit fly to ask to which extent activity modulates neuronal morphology and
connectivity during development. Further, we summarize the evidence indicating
that the adult nervous system of flies retains some capacity for structural
plasticity at the synaptic or circuit level. For simplicity, we selected examples
mostly derived from studies on the visual system and on the mushroom body, two
regions of the fly brain with extensively studied neuroanatomy.
PMID- 29960598
TI - The influence of the intestinal microflora to the efficacy of Rosuvastatin.
AB - BACKGROUND: Intestinal microflora has been shown to play essential roles in the
clinical therapies of metabolic diseases. The present study is aiming to
investigate the potential roles and mechanisms of how intestinal microflora
mediates lipid-reduction efficacy of Rosuvastatin. METHODS: To investigate the
correlation between the intestinal microflora and efficacy of Rosuvastatin, we
analyzed the diversity of intestinal microflora using PCR-DGGE analysis and 16S
rDNA sequencing approaches. Furthermore, we compared the blood lipid levels of
rat models with dysbiosis of intestinal microflora and control rats upon the
Rosuvastatin administration. RESULTS: The diversity of the intestinal flora was
obviously decreased upon the antibiotic treatment, this effect could be
maintained for 2 weeks after establishment of the models. Importantly, the
results from 16S rDNA sequencing demonstrated that the abundance of Lactobacillus
and Bifidobacterium was remarkably diminished upon the antibiotic treatment in
antibiotic+Rosuvastatin-treated group compared to that of Rosuvastatin-treated
group and control group. Correspondently, the lipid-reduction efficacy of
Rosuvastatin was significantly compromised. However, the diversity of the
intestinal flora was recovered 4 weeks after the antibiotic treatment.
Subsequently, the lipid-reduction efficacy of Rosuvastatin was also recovered to
level of the control rats treated with Rosuvastatin alone. CONCLUSION: Intestinal
flora could play an essential role in mediating the lipid-reduction efficacy of
Rosuvastatin.
PMID- 29960599
TI - Development of an evidence-based brief 'talking' intervention for non-responders
to bowel screening for use in primary care: stakeholder interviews.
AB - BACKGROUND: Bowel cancer is the third most common cause of cancer death
worldwide. Bowel screening has been shown to reduce mortality and primary care
interventions have been successful in increasing uptake of screening. Using
evidence-based theory to inform the development of such interventions has been
shown to increase their effectiveness. This study aimed to develop and refine a
brief evidence-based intervention for eligible individuals whom have not
responded to their last bowel screening invitation (non-responders), for
opportunistic use by primary care providers during routine consultations.
METHODS: The development of a brief intervention involving a conversation between
primary care providers and non-responders was informed by a multi-faceted model
comprising: research team workshop and meetings to draw on expertise; evidence
from the literature regarding barriers to bowel screening and effective
strategies to promote informed participation; relevant psychological theory, and
intervention development and behaviour change guidance. Qualitative telephone
interviews with 1) bowel screening stakeholders and 2) patient non-responders
explored views regarding the acceptability of the intervention to help refine its
content and process. RESULTS: The intervention provides a theory and evidence
based tool designed to be incorporated within current primary care practice.
Bowel screening stakeholders were supportive of the intervention and recognised
the importance of the role of primary care. Interviews highlighted the importance
of brevity and simplicity to incorporate the intervention into routine clinical
care. Non-responders similarly found the intervention acceptable, valuing a
holistic approach to their care. Moreover, they expected their primary care
provider to encourage participation. CONCLUSIONS: A theory-based brief
conversation for use in a primary care consultation was acceptable to bowel
screening stakeholders and potential recipients, reflecting a health promoting
primary care ethos. Findings indicate that it is appropriate to test the
intervention in primary care in a feasibility study.
PMID- 29960600
TI - Structural validity of the Dutch version of the disability of arm, shoulder and
hand questionnaire (DASH-DLV) in adult patients with hand and wrist injuries.
AB - BACKGROUND: Fractures of the hand and wrist are one of the most common injuries
seen in adults. The Disabilities of the Arm, Shoulder and Hand (DASH)
questionnaire has been developed as a patient-reported assessment of pain and
disability to evaluate the outcome after hand and wrist injuries. Patient
reported outcomes (PROs) can be interpreted as pain, function or patient
satisfaction. To be able to interpret clinical relevance of a PRO, the structural
validity and internal consistency is tested. The Dutch version of the DASH has
not yet been validated. The aim of this study was to evaluate the structural
validity and the internal consistency of the existing Dutch version of the DASH.
The relevance of reporting subscale scores was investigated. METHODS: This study
was a retrospective analysis of cross-sectional data of 370 patients with an
isolated hand or wrist injury. Adult patients aged 18 to 65 years treated
conservatively or surgically were included. Patients unable to understand or read
the Dutch language were excluded. Confirmatory factor analysis was used to
investigate the structural validity, while Cronbach's alpha and coefficient omega
were used to assess internal consistency. RESULTS: All investigated models (a
single factor model, a 3-correlated factor, and a bifactor model) were associated
with a good model fit. Both the single factor and the 3-correlated factor model
were associated with factor loadings of at least 0.70. In addition, the
covariance between the factors in the 3-correlated factor model was positive (at
least 0.89) and statistically significant (p < 0.001). In the bifactor model, the
additional value of subscales was limited as the items loaded high on the general
factor but low on the subscale factors. CONCLUSION: This study indicates that the
Dutch version of the DASH should be considered as an unidimensional trait. A
single score should be reported.
PMID- 29960601
TI - Asymptomatic progressive multifocal leukoencephalopathy: a case report and review
of the literature.
AB - BACKGROUND: We report the development of asymptomatic progressive multifocal
leukoencephalopathy in a patient with multiple sclerosis on natalizumab therapy.
Progressive multifocal leukoencephalopathy often presents with debilitating
neurologic symptoms. Very few cases have documented a completely asymptomatic
course of the disease. CASE PRESENTATION: A 26-year-old white woman with multiple
sclerosis was treated with natalizumab. She was diagnosed as having progressive
multifocal leukoencephalopathy based on characteristic magnetic resonance imaging
lesions after 27 infusions of natalizumab. She had no neurologic deficits at the
time of diagnosis and John Cunningham virus in cerebrospinal fluid was detected
at 15 copies/ml. She was initially treated with mefloquine and mirtazapine and
remained asymptomatic for 3 months. She later developed worsening magnetic
resonance imaging lesions related to immune reconstitution inflammatory syndrome.
At that time, she received intravenously administered immunoglobulin and high
dose intravenously administered methylprednisolone with radiologic improvement of
the lesions. CONCLUSIONS: Our case report illustrates that early detection of
asymptomatic progressive multifocal leukoencephalopathy and its subsequent
treatment resulted in a benign clinical course. In consideration of the
additional small number of cases of asymptomatic progressive multifocal
leukoencephalopathy that have been reported, we conclude that routine magnetic
resonance imaging surveillance is important for patients with multiple sclerosis
who are at high risk for developing natalizumab-associated progressive multifocal
leukoencephalopathy.
PMID- 29960603
TI - Dosage of pain rehabilitation programs: a qualitative study from patient and
professionals' perspectives.
AB - BACKGROUND: There is a large and unexplained practice variation in prescribed
dosages of pain rehabilitation programs (PRP), and evidence regarding the optimum
dosage is unknown. METHODS: To explore perspectives of patients and
rehabilitation professionals regarding dosages of PRP an explorative qualitative
research design was performed with thematic analysis. Patients and rehabilitation
professionals were recruited from three rehabilitaton centers in the Netherlands.
A purposive sample of patients who completed a PRP, with a range of personal and
clinical characteristics was included. Rehabilitation professionals from all
different disciplines, working within multidisciplinary PRP for a minimum of two
years, for at least 0.5 fte were included. Individual semi-structured interviews
were conducted with 12 patients undergoing PRP, and three focus groups were
formed with a total of 17 rehabilitation professionals involved in PRP. RESULTS:
All patients were satisfied with received dosage. Factors important in relation
to dosage of PRP were categorized into patient related characteristics (case
complexity from a biopsychosocial perspective) to treatment related
characteristics (logistics and format of the program, interaction between
patients and professionals), and external factors (support from others, costs,
traveling distance and injury compensation). Professionals concluded that dosage
was currently based on historical grounds and clinical expertise. CONCLUSION:
Patients and professionals from different centers considered the same factors
related to dosage of PRP, but these considerations (from patients and
professionals) led to different dose choices between centers. PRP dosage appeared
to be mainly based on historical grounds and clinical expertise. The insights of
this study could assist in future research regarding optimum dosage of PRP and
rehabilitation programs in general.
PMID- 29960605
TI - Impact of a tailored activity counselling intervention during inpatient
rehabilitation after knee and hip arthroplasty - an explorative RCT.
AB - BACKGROUND: The aim of the study was to improve physical activity (PA), well
being and clinical outcome after total knee and hip arthroplasty through tailored
activity counselling during inpatient rehabilitation. METHODS: 65 patients (aged
70.4 +/- 7.3 years, BMI 28.5 +/- 4.3) starting inpatient rehabilitation after
primary knee or hip arthroplasty due to osteoarthritis were recruited and pseudo
randomized into an intervention (IG) and a control group (CG). Twice a week, the
IG was encouraged to increase their daily step count by 5%. PA, e. g. number of
steps, step frequency, or active minutes, was measured by step activity
monitoring. Well-being and clinical outcome were assessed using the SF-36, Oxford
Knee/Hip Score and Global rating of Change. Procedures were conducted at the
onset of inpatient rehabilitation, and repeated one and 6 months after inpatient
rehabilitation. RESULTS: Data sets were obtained from 49 patients (IG: n = 23,
CG: n = 26). Both groups significantly increased their number of daily steps from
the 1 month to the 6 months follow up after rehabilitation: CG: 9019 (95%CI:
7812, 10,226), IG: 9280 (7972, 10,588) and CG: 10921 (9571, 12,271), IG: 11326
(9862, 12,791) respectively. Additionally, well-being and clinical outcome
improved significantly in both groups. No significant differences in physical
activity, clinical outcome and well-being were found between the groups.
CONCLUSIONS: PA counselling during inpatient rehabilitation does not improve PA,
well-being and clinical outcome in patients with primary knee or hip arthroplasty
in addition to the rehabilitation program. PA interventions may be more effective
after the completion of the inpatient rehabilitation phase. TRIAL REGISTRATION:
DRKS DRKS00012682 . Registered retrospectively on 03-07- 2017.
PMID- 29960604
TI - Plasma amyloid-beta levels, cerebral atrophy and risk of dementia: a population
based study.
AB - BACKGROUND: Plasma amyloid-beta (Abeta) levels are increasingly studied as a
potential accessible marker of cognitive impairment and dementia. However, it
remains underexplored whether plasma Abeta levels including the novel Abeta
peptide 1-38 (Abeta1-38) relate to preclinical markers of neurodegeneration and
risk of dementia. We investigated the association of plasma Abeta1-38, Abeta1-40,
and Abeta1-42 levels with imaging markers of neurodegeneration and risk of
dementia in a prospective population-based study. METHODS: We analyzed plasma
Abeta levels in 458 individuals from the Rotterdam Study. Brain volumes,
including gray matter, white matter, and hippocampus, were computed on the basis
of 1.5-T magnetic resonance imaging (MRI). Dementia and its subtypes were defined
on the basis of internationally accepted criteria. RESULTS: A total of 458
individuals (mean age, 67.8 +/- 7.7 yr; 232 [50.7%] women) with baseline MRI
scans and incident dementia were included. The mean +/- SD values of Abeta1-38,
Abeta1-40, and Abeta1-42 (in pg/ml) were 19.4 +/- 4.3, 186.1 +/- 35.9, and 56.3
+/- 6.2, respectively, at baseline. Lower plasma Abeta1-42 levels were associated
with smaller hippocampal volume (mean difference in hippocampal volume per SD
decrease in Abeta1-42 levels, - 0.13; 95% CI, - 0.23 to - 0.04; p = 0.007). After
a mean follow-up of 14.8 years (SD, 4.9; range, 4.1-23.5 yr), 79 persons
developed dementia, 64 of whom were diagnosed with Alzheimer's disease (AD).
Lower levels of Abeta1-38 and Abeta1-42 were associated with increased risk of
dementia, specifically AD (HR for AD per SD decrease in Abeta1-38 levels, 1.39;
95% CI, 1.00-2.16; HR for AD per SD decrease in Abeta1-42 levels, 1.35; 95% CI,
1.05-1.75) after adjustment for age, sex, education, cardiovascular risk factors,
apolipoprotein E epsilon4 allele carrier status, and other Abeta isoforms.
CONCLUSIONS: Our results show that lower plasma Abeta levels were associated with
risk of dementia and incident AD. Moreover, lower plasma Abeta1-42 levels were
related to smaller hippocampal volume. These results suggest that plasma Abeta1
38 and Abeta1-42 maybe useful biomarkers for identification of individuals at
risk of dementia.
PMID- 29960602
TI - Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers.
AB - Extracellular vesicles (EVs) are heterogeneous, nano-sized vesicles that are shed
into the blood and other body fluids, which disperse a variety of bioactive
molecules (e.g., protein, mRNA, miRNA, DNA and lipids) to cellular targets over
long and short distances. EVs are thought to be produced by nearly every cell
type, however this review will focus specifically on EVs that originate from
cells at the interface of CNS barriers. Highlighted topics include, EV
biogenesis, the production of EVs in response to neuroinflammation, role in
intercellular communication and their utility as a therapeutic platform. In this
review, novel concepts regarding the use of EVs as biomarkers for BBB status and
as facilitators for immune neuroinvasion are also discussed. Future directions
and prospective are covered along with important unanswered questions in the
field of CNS endothelial EV biology.
PMID- 29960606
TI - Second Malignancies Following Childhood Cancer Treatment in Germany From 1980 to
2014.
AB - BACKGROUND: Because of improvements in cancer treatment, more than 80% of all
children with cancer now survive at least five years from the time of diagnosis.
As a result, late sequelae of cancer and its treatment have become more common,
particularly second malignancies. We studied the current incidence of second
malignancies among childhood cancer survivors in Germany. METHODS: This study is
based on the cohort of the German Childhood Cancer Registry (Deutsches
Kinderkrebsregister, DKKR). Persons given the diagnosis of a first malignancy at
any time in the years 1980-2014 who were no more than 14 years old at the time of
diagnosis and survived at least six months thereafter were included in the study.
Cumulative incidences and hazard ratios were calculated, and comparisons with the
general population were made with the aid of standardized incidence ratios (SIR).
RESULTS: Among the 47 650 survivors included in the study, there were 1262 cases
of second malignancies. After a follow-up interval of up to 35 years, the
cumulative incidence of second malignancies was 8.27% (95% confidence interval
[7.51; 9.03]). Second malignancies were more common in female patients (hazard
ratio 1.29, [1.16; 1.44]) and in those who had had a systemic cancer as their
initial malignancy (hazard ratio 1.22 [1.09; 1.36]). The SIR compared to the
general population for the period 1955-2014 was 7.08 [6.42; 7.9] for female
patients and 5.83 [5.27; 6.42] for male patients. CONCLUSION: The cumulative
incidence of second malignancies is 5.4% at 25 years and 8.3% at 35 years; these
figures may be slight underestimates. The DKKR is an epidemiologic registry
containing no data about treatment, so the effect of treatment on the risk of
second malignancies could not be studied. The acquisition and evaluation of
treatment data for the overall cohort is currently one of the main tasks for
research on the late sequelae of childhood cancer. This may enable conclusions to
be drawn about whether treatment strategies that have been introduced to lessen
the risk of a second malignancy actually have the desired effect.
PMID- 29960607
TI - Frequent Adverse Drug Reactions, and Medication Groups under Suspicion.
AB - BACKGROUND: The adverse drug reaction database of the German Federal Institute
for Drugs and Medical Devices (Bundesinstitut fur Arzneimittel und
Medizinprodukte, BfArM) contains reports of suspected adverse drug reactions
(ADRs) that are spon- taneously submitted by physicians, pharmacists, or
patients. The aim of the present study was a descriptive analysis of all of these
spontaneous reports. METHODS: 345 662 spontaneously submitted reports were
analyzed with respect to the number of reports per year, the sources of the
reports, demographic variables, the most commonly reported ADRs, and the drug
classes most commonly suspected. RESULTS: The number of reports submitted
spontaneously each year has grown steadily since 1978. At the least detailed
level of analysis, "drugs for the treatment of nervous system disorders" were the
most common class of drugs under suspicion of causing the reported adverse drug
reactions (23.1%). In a more detailed analysis by therapeutic subgroup, the three
subgroups most commonly reported as suspected of causing side effects were
antithrombotic agents, systemic antibiotics, and psycholeptics-causing
thrombocytopenia, diarrhea, and drug dependency as the most frequently reported
ADRs, respectively. The order of drug classes most commonly causing ADRs differed
markedly between the physicians' reports (diazepines, fluoroquinolones, heparins)
and the patients' reports (interferons, anti- thrombotic drugs, selective
immunosuppressant drugs). Patients more commonly reported subjectively perceived
ADRs, while physicians more commonly reported findings or diagnoses that require
medical expertise. CONCLUSION: The increasing number of spontaneous reports is
mainly due to reports forwarded from pharmaceutical companies to the BfArM. This,
in turn, is probably a result of increasingly strict legal reporting requirements
in Germany. The detected differences between physicians' and patients' ADR
reports can be taken to indicate that patients should be more specifically
informed and questioned about potential ADRs. By reporting adverse drug
reactions, physicians may improve drug safety.
PMID- 29960608
TI - Heart failure symptom science: Is adrenergic dysregulation a missing link?
PMID- 29960609
TI - Caring for yourself leads to better outcomes for patients.
PMID- 29960610
TI - Heart Teams: A New Paradigm in Health Care.
PMID- 29960611
TI - Predictors of Cardiorespiratory Fitness Improvements With Cardiac Rehabilitation:
Lower Baseline Fitness With the Most to Gain, Gains the Most.
PMID- 29960612
TI - Decision Support Tools, Systems, and Artificial Intelligence in Cardiac Imaging.
AB - Noninvasive cardiac imaging is widely used for the diagnosis and management of
cardiac patients. The increasing demand for cardiac imaging begins to exceed the
number of available interpreting physicians, leaving less time to interpret
studies. In addition, the busy clinician is facing the increasingly daunting task
of keeping abreast of current medical advancements and the ongoing changes in
disease diagnosis and therapy. Committing to memory and recalling such large
volumes of information is challenging and is responsible for difficulties in
adopting the rapid changes in imaging practice, and is likely partially
responsible for errors in patient diagnosis and management. Diagnostic errors
rank high in the cause of death in the United States, and are more common than
any other medical error and are responsible for most malpractice claims. Most of
these errors are related to cognitive errors. The use of artificial intelligence
systems that can serve as complementary methods to assist humans with decision
making can potentially prevent these errors. The past decades witnessed the
development and integration of these tools, which can assist physicians with
image interpretation. These tools work to optimize image quality for better
visualization and accompany all imaging modalities, starting from patient
selection for the appropriate test, patient preparation, image acquisition,
processing, and finally interpretation. Current and future directions for
technologies that support cardiac imaging physicians are discussed in this
review.
PMID- 29960613
TI - "NEW" Prehabilitation: A 3-Way Approach to Improve Postoperative Survival and
Health-Related Quality of Life in Cardiac Surgery Patients.
AB - With advances in health care practices and delivery, the overall life expectancy
of the Western population has increased. For those practitioners involved in the
care of the patient with advanced cardiac disease, there has been a resultant
higher prevalence of increasingly frail and older patients undergoing complex
cardiac procedures. The higher rates of comorbid-associated higher vulnerability,
with associated deconditioning, predisposes older, frail patients to poorer
postoperative outcomes and a complicated recovery process after cardiac surgery.
In addition, such patients experience inferior quality of life as a result of
reduced ability to independently perform activities of daily living. During the
preoperative waiting period, the cardiac symptoms and anxiety induces inactivity
that in turn compounds the physical and mental deconditioning. To improve
functional capacity and enhance postoperative recovery, prehabilitation, a
component of the enhanced recovery after surgery model, might be of particular
importance. In some studies, the preoperative improvement of the baseline
physical, nutritional, and mental status has been reported to improve
postoperative outcomes and enhance recovery after cardiac surgery. To address
these domains, a 3-way approach to prehabilitation that is targeted toward
improving nutritional status (N), exercise capacity (E) and worry reduction (W)
(nutrition, exercise, and worry; "NEW" approach) might facilitate the
perioperative management by ameliorating the postoperative outcomes and
alleviating the surgical stress-related health deconditioning. In this review,
the NEW approach and its potential benefits on postoperative outcomes as well as
an implementation model (Promoting Action on Research Implementation in Health
Services [PARiHS] framework) to aid institutional level implementation is
described.
PMID- 29960615
TI - The Spoke-Hub-and-Node Model of Integrated Heart Failure Care.
AB - Heart failure (HF) is a significant public health concern. Specialized HF clinics
provide the optimal environment to address the complex needs of these patients
and improve outcomes. The current and growing population of patients with HF
outstrips the ability of these clinics to deliver care. Integrated care is
defined as health services that are managed and delivered so that people receive
a seamless continuum of health promotion, disease prevention, diagnosis,
treatment, disease management, rehabilitation, and palliative care services. This
approach requires coordination across different levels and sites of care within
and beyond the health sector, according to changing patient needs throughout
their lives. The spoke-hub-and-node (SHN) model represents an organization of
care that works collaboratively with the primary care sector and is highly
integrated with community-based multidisciplinary teams of health care
professionals and specialty care. The purpose of this article is to analyze the
requirements for successful implementation of SHN models. We consider the
respective roles of HF clinics, HF nurse specialists, pharmacists, palliative
care teams, telemonitoring, and solo practitioners. We also discuss levels of
care delivery and the importance of patient stratification and patient flow. The
SHN approach has the potential to build on and improve the chronic care model
(CCM) to deliver centralized services to preserve high-quality patient-centred
care at affordable costs.
PMID- 29960614
TI - Postoperative Remote Automated Monitoring: Need for and State of the Science.
AB - Worldwide, more than 230 million adults have major noncardiac surgery each year.
Although surgery can improve quality and duration of life, it can also
precipitate major complications. Moreover, a substantial proportion of deaths
occur after discharge. Current systems for monitoring patients postoperatively,
on surgical wards and after transition to home, are inadequate. On the surgical
ward, vital signs evaluation usually occurs only every 4-8 hours. Reduced in
hospital ward monitoring, followed by no vital signs monitoring at home, leads to
thousands of cases of undetected/delayed detection of hemodynamic compromise. In
this article we review work to date on postoperative remote automated monitoring
on surgical wards and strategy for advancing this field. Key considerations for
overcoming current barriers to implementing remote automated monitoring in Canada
are also presented.
PMID- 29960616
TI - Heart Failure Management in Nursing Homes: A Scoping Literature Review.
AB - Heart failure (HF) affects 20% of nursing home (NH) residents, causing high
morbidity and mortality. The optimal approach to HF management in NHs remains
elusive. We conducted a scoping review of published guidelines and HF management
interventions in NHs. A search for English publications since 1990 was conducted
using PubMed, EMBASE, CINAHL, and Scopus, for scientific statements, guidelines,
recommendations, or intervention studies that addressed at least 1 principle of
HF management. Of 2545 records retrieved, 19 articles were retained after
screening, and 2 additional articles identified through reference list manual
searches. Six articles represented 5 guidelines and 15 described interventions.
All guidelines endorsed the applicability of general HF guidelines to NH
residents, tailored to comorbidities, frailty, and advance care preferences. Four
addressed quality assurance but not feasibility and sustainability.
Methodological quality of the interventions was poor, although results suggest
that guideline-based HF management in NHs can improve nursing staff knowledge and
job satisfaction, prescribing, and reduce acute care utilization. Clinically
based education for staff, and access to specialist mentorship are important. NH
physician involvement was limited, and resident/family education potentially
ineffective. Concerns about feasibility, sustainability, and quality assurance
were identified in most interventions, and advance care planning was rarely
addressed. HF guidelines for NH support the applicability of general HF
guidelines to the care of NH residents, and published interventions suggest that
guideline-based HF management in NHs is effective. Future work should support
greater physician and resident engagement, advance care planning, and provide
robust guidelines on developing feasible and sustainable interventions.
PMID- 29960617
TI - Interventions to Mobilize Elderly Patients and Reduce Length of Hospital Stay.
AB - For older people, and in particular frail older people, acute illness and
hospitalization are associated with significant potential harm. One of the major
drivers of iatrogenic harm in older adults is hospital-induced immobility, the so
called "pajama paralysis." Older people in hospital are often confined to bed
even after their acute illness has improved; not only by physical factors such as
potentially unnecessary urinary catheters and monitoring equipment but also by
the culture often found in hospital of keeping patients in bed for most of the
day. Bed rest is associated with sarcopenia, infections, and greater length of
stay, and early mobilization of patients is often overlooked as an intervention,
despite being inexpensive and effective. In this article we review the evidence
of the harm of unnecessary immobilization and discuss the innovations that have
been developed to encourage a cultural shift away from pajama paralysis and
toward early mobilization of older people in hospital.
PMID- 29960618
TI - New Dimensions in Palliative Care Cardiology.
AB - The landscape of patient care at the beginning of the 19th century was
dramatically different than it is today. With few good treatment options, illness
courses were generally brief. Near the end of life, patients were attended to by
spiritual advisors, not health care professionals. Death typically occurred at
home, surrounded by friends and family. Moving to the present time, decades of
medical advances have significantly improved life expectancy. Cardiology has
particularly benefited from many of these advances. Cardiac patients are
initiated on optimal medication regimens. As disease burdens progress,
interventions such as implantable defibrillators and cardiac resynchronization
pacing systems become options for many patients. With further clinical
deterioration, select patients might be candidates for ventricular assist devices
and heart transplants. These advances have unquestionably improved the prognosis
with advanced cardiovascular illnesses. However, they have also changed patient
and family attitudes about death and dying, to the point where we have
effectively "medicalized our mortality." The importance of introducing palliative
care to the cardiac patient population is now well recognized, with the major
cardiovascular societies incorporating palliative care principles into their
guideline and consensus statement documents. However, despite this recognition,
few cardiac patients get access to palliative care and other resources such as
hospice. In this article the existing literature on this topic is reviewed and
opportunities for developing and fostering a more collaborative relationship
between the disciplines of cardiology and palliative care are discussed.
PMID- 29960619
TI - Variation in Preparticipation Screening Medical Questionnaires and Physical
Examinations Across Canadian Universities.
AB - Pre-participation screening of athletes to prevent sudden cardiac arrest or death
is endorsed by international guidelines. Standardized histories and physical
examinations are recommended to optimize effectiveness. To assess current
screening practices across Canada in the university athlete population, we sought
to analyze the preparticipation screening form of all universities. A comparative
analysis to recommendations from the American Heart Association (AHA), European
Society of Cardiology (ESC), and the Preparticipation Physical Evaluation (PPE-4)
was conducted. Pre-participation forms from 30 of 56 U Sports universities were
obtained. Adherence to published guidelines was highly variable. Ten percent
strictly followed any of the 3 guideline recommendations, and only 43% contained
at least 75% of the recommended items. Average percentage adherence to AHA and
ESC guidelines was statistically significantly higher than adherence to the PPE-4
(62.2% and 66.1%, respectively, vs 52.7%, P < 0.001). Family history of common
cardiac conditions predisposing athletes to sudden cardiac death and family
history of sudden or unexpected death was omitted in 80% and 30% of forms,
respectively. Recommendations for examining for stigmata of Marfan syndrome and
assessment of femoral pulses was absent on more than 70% of forms. Although there
is great controversy regarding the benefits and impact of screening, our results
suggest that Canadian universities are conducting pre-participation screening
although in a highly variable manner. Incomplete and variable screening
questionnaires employed by Canadian universities may negatively affect the
potential to identify athletes with underlying disease. We recommend that, if pre
participation screening is performed, a guideline-based questionnaire be used to
optimize accuracy.
PMID- 29960620
TI - Geographical Differences in Comorbidity Burden and Outcomes in Adults With
Syncope Hospitalizations in Canada.
AB - A recent study found that rates of hospitalization for syncope vary across
provinces; however, it is unknown whether differences in comorbidity burden and
outcomes also exist. The Canadian Institute for Health Information Discharge
Abstract Database was used to identify primary syncope hospitalizations (ICD-10
code R55) from 2004 to 2013 for all provinces (except Quebec). Charlson
comorbidity score was calculated from comorbidities at the time of
hospitalization. Outcomes were defined as in-hospital mortality, 30-day
readmission for any cause, and syncope. Logistic regression models were
constructed for odds ratios (ORs) and 95% confidence intervals (CIs) to estimate
interprovincial differences in outcomes. The interprovincial range (IPR) for mean
age was 61.1 +/- 17.5 to 73.7 +/- 16.3 years, and at least half were male
patients. There were significant differences in comorbidity burden across
provinces (P < 0.01); however, the majority of patients had a Charlson
comorbidity score = 0 (IPR, 53.9%- 71.9%). In multivariable analysis, compared
with Ontario, in-hospital mortality was higher for British Columbia (OR, 1.59;
95% CI, 1.22-2.06), Nova Scotia (OR, 1.67; 95% CI, 1.05-2.65), and Newfoundland
(OR, 2.27; 95% CI, 1.29-4.00); 30-day readmission for any cause was higher for
British Columbia (OR, 1.15; 95% CI, 1.06-1.26), Alberta (OR, 1.19; 95% CI, 1.07
1.31), Manitoba (OR, 1.36; 95% CI, 1.18-1.56), and Prince Edward Island (OR,
1.38; 95% CI, 1.0-1.89), and all outcomes were higher in Saskatchewan. There is
significant interprovincial heterogeneity in comorbidity burden and outcomes for
hospitalizations for syncope. Future research evaluating whether standardized
practices for management of syncope reduce variability and improve healthcare
utilization and costs is needed.
PMID- 29960621
TI - Stroke Prevention for High-Risk Atrial Fibrillation in the Emergency Setting:
Differences Between Canada and the United States.
PMID- 29960622
TI - Reply to Kea et al.-Stroke Prevention for High-Risk Atrial Fibrillation in the
Emergency Setting: Differences Between Canada and the US.
PMID- 29960623
TI - Development of a Virtual Radiation Oncology Clinic for training and simulation of
errors in the radiation oncology workflow.
PMID- 29960624
TI - Review of thoracic reirradiation with stereotactic body radiation therapy: A
focus on toxicity risks.
AB - Reirradiation of thoracic malignancies is clinically challenging in balancing the
risks and efficacy. Stereotactic body radiation therapy (SBRT) can facilitate
ablative dosing of discrete targets while minimizing normal tissue exposure;
thus, SBRT is an attractive, minimally invasive option to consider for patients
with recurrent or new malignancies within a previously irradiated field.
Published data are summarized from 28 studies on the use of SBRT for thoracic
reirradiation. We review clinical outcomes with a primary focus on toxicity
risks, dosimetric correlates of normal tissue complication probability (NTCP),
and other factors that correlate with NTCP. Meaningful compilation of published
data on reirradiation with SBRT is limited because of the retrospective nature of
published studies, which include mostly small numbers of patients, with various
clinical scenarios and SBRT dosing and techniques. Nevertheless, these studies
show that thoracic reirradiation with SBRT is feasible, with relatively favorable
outcomes. Yet, severe to fatal toxicities do occur, and dosimetric measures to
predict severe toxicity are poorly characterized, necessitating further study to
better characterize predictive factors for NTCP.
PMID- 29960625
TI - Preoperative contralateral lung radiation dose is associated with postoperative
pulmonary toxicity in patients with locally advanced non-small cell lung cancer
treated with trimodality therapy.
AB - PURPOSE: In patients with non-small cell lung cancer (NSCLC) who undergo
trimodality therapy (chemoradiation followed by surgical resection), it is
unknown whether limiting preoperative radiation dose to the uninvolved lung
reduces postsurgical morbidity. This study evaluated whether radiation fall-off
dose parameters to the contralateral lung that is unaffected by NSCLC are
associated with postoperative complications in NSCLC patients treated with
trimodality therapy. METHODS AND MATERIALS: We retrospectively reviewed NSCLC
patients who underwent trimodality therapy between March 2008 and October 2016,
with available restored digital radiation plans. Fischer's exact test was used to
assess associations between patient and treatment characteristics and the
development of treatment-related toxicity. Spearman rank correlation was used to
measure the strength of association between dosimetric parameters. RESULTS: Forty
six patients were identified who received trimodality therapy with intensity
modulated radiation (median, 59.4 Gy; range, 45-70) and concurrent platinum
doublet chemotherapy, followed by surgical resection. The median age was 64.9
years (range, 45.6-81.6). The median follow-up time was 1.9 years (range, 0.3
8.4). Twenty-four (52.2%) patients developed any-grade pulmonary toxicity and 14
(30.4%) patients developed grade 2+ pulmonary toxicity. There was an increased
incidence of any-grade pulmonary toxicity in patients with contralateral lung
volume receiving at least 20 Gy (V20) >=7% compared with <7% (90%, n = 9 vs
41.7%, n = 15; P = .01). Similarly, contralateral lung V10 >=20% was associated
with an increased rate of any-grade pulmonary toxicity compared with V10 <20%
(80%, n = 12 vs 38.7%, n = 12; P = .01). Pneumonectomy/bilobectomy was associated
with grade 2+ pulmonary toxicity (P = .04). CONCLUSIONS: Patients who received a
higher radiation fall-off dose volume parameter (V20 >=7% and V10 >=20%) to the
contralateral uninvolved lung had a higher incidence of any-grade postoperative
pulmonary toxicity. Limiting radiation fall-off dose to the uninvolved lung may
be an important modifiable radiation parameter in limiting postoperative toxicity
in trimodality patients.
PMID- 29960626
TI - Psychometric Validation of the Sexual Distress Scale in Men with Prostate Cancer.
AB - BACKGROUND: Different scales exist for the assessment of sexual distress in men
with prostate cancer (PCa); however, these measures narrowly focus on distress
associated with sexual function. AIM: To validate and examine the psychometric
properties of the Sexual Distress Scale (SDS) and Sexual Distress Scale-Revised
(SDS-R), which were recently validated for use within men, in samples of sexually
functional and sexually dysfunctional men with PCa. METHODS: A sample of 538 men
(with and without PCa and with and without sexual dysfunction) were used to
examine the psychometric properties of the SDS. Confirmatory factor analysis
followed by tests of measurement bias, calculations of reliability, and
estimation of receiver operating characteristic (ROC) curves were used to examine
the psychometric properties of the SDS and SDS-R. A subsample of 321 men
completed the survey again 1 month later, and their responses were used to
examine test-retest reliability. OUTCOMES: Participants completed the SDS and SDS
R, as well as measures of sexual bother and sexual concerns, sexual function,
sexual attitudes, and mood states. RESULTS: The SDS and SDS-R assess 1 general
domain of sexual distress; 1 violation of measurement invariance was found
between men with and men without PCa, which limits the comparability of scores
between these 2 groups. Internal consistency and test-retest reliabilities were
above 0.93 and 0.82, respectively. Evidences of validity based on relations with
other variables supported our predictions because sexual distress was associated
with other measures of distress, sexual function, satisfaction, and mood and not
correlated to sexual attitudes. Although the SDS and SDS-R discriminated between
sexually functional and dysfunctional men, the accuracy of the cutoff scores was
only moderate. CLINICAL TRANSLATION: This instrument can be used by researchers
and clinicians to examine sexual distress and can be used to elucidate how sexual
distress relates to sexual function, well-being, and quality of life. STRENGTHS
AND LIMITATIONS: The SDS and SDS-R assess sexual distress independently of sexual
function; however, with the current evidence, they should not be used to compare
men with and men without PCa and to classify men with and men without sexual
dysfunction. CONCLUSION: This study provides a validation of the SDS and SDS-R
that can be used in samples of men with PCa and with and without sexual
dysfunction for the assessment of distress. Santos-Iglesias P, Walker LM.
Psychometric Validation of the Sexual Distress Scale in Men with Prostate Cancer.
J Sex Med 2018;15:1010-1020.
PMID- 29960628
TI - Erratum.
PMID- 29960629
TI - High Prevalence of Erectile Dysfunction in Diabetic Men With Depressive Symptoms:
A Meta-Analysis.
AB - BACKGROUND: Erectile dysfunction (ED) may be common among diabetic men with
depressive symptoms (DS), but its prevalence is still debated. AIM: To conduct a
meta-analysis of the prevalence of ED in diabetic men with DS compared to those
without DS, calculating the relative odds ratios (ORs) and 95% CIs. METHODS:
PubMed, MEDLINE, Embase, and Web of Science were searched up to January 2018. All
the studies assessing the risk of ED among diabetic men having DS were reviewed.
2 Authors independently assessed literature and extracted information
eligibility. Any disagreement was resolved by a third reviewer. Newcastle-Ottawa
quality assessment scale was used to evaluate study quality in meta-analyses. We
calculated the ORs with 95% CIs using software Stata, Version 12.0; StataCorp,
College Station, TX). Data were pooled using a fixed or random effects model
according to heterogeneity. Sensitivity analyses were conducted to assess
potential bias. This study was conducted according to the guidelines for Meta
Analyses and Systematic Reviews of Observational Studies. OUTCOMES: The strength
of the association between DS and the prevalence of ED was evaluated using ORs
and 95% CIs. RESULTS: 5 Studies were eligible for the present analysis, reporting
on a total of 2525 diabetic men. Mean age of patients ranged from 42.37-61.65
years in the included studies. The overall prevalence of ED in diabetic men with
DS was 74.2% (95% CI 59.0-89.4). The overall prevalence of ED in diabetic men
without DS was 37.4% (95% CI 16.2-58.6). The pooled crude OR for these 5 studies
was 6.40 (95% CI 2.11-19.38, P < .05, I2 = 94.6%). The pooled OR of 4 multi
variate analyses was 3.08 (95% CI 1.32-4.85, P < .001, I2 = 83.5%). CLINICAL
IMPLICATIONS: Diabetic men with DS had a significantly increased prevalence of
ED, suggesting that ED should be of concern to clinicians when managing diabetic
men with DS. STRENGTHS & LIMITATIONS: A strength of this study is that it is the
first meta-analysis to assess the prevalence of ED in diabetic men with DS and
quantitatively analyze the association between DS and ED risk among diabetic men.
A limitation is that all included studies were cross-sectional studies, which may
generate bias. CONCLUSION: The present meta-analysis of 5 cross-sectional studies
suggests that diabetic men showing DS, compared to the diabetic men without DS,
have more risk of ED. Further larger prospective cohorts with more power or meta
analysis based on individual patient data need to be conducted to confirm this
association. Wang X, Yang X, Cai Y, et al. High Prevalence of Erectile
Dysfunction in Diabetic Men With Depressive Symptoms: A Meta-Analysis. J Sex Med
2018;15:935-941.
PMID- 29960627
TI - Biomechanical Comparison of Inflatable Penile Implants: A Cadaveric Pilot Study.
AB - BACKGROUND: Throughout the last decade there has been a growing interest in the
biomechanical differences between inflatable penile prostheses (IPPs) and their
significance with regard to the patient experience. AIM: To present our findings
assessing the biomechanical properties of IPPs with and without rear tip
extenders (RTEs). METHODS: This is a biomechanical study of the 3 most commonly
used IPPs (AMS CX, AMS LGX, and Coloplast Titan) as assessed by column
compression, modified cantilever deflection, and 3-point bending methods. The
IPPs were surgically placed into 3 fresh cadavers via an infrapubic technique by
a single large-volume implanter. A biomechanical evaluation of the properties of
each IPP inside the fibroelastic tunica albuginea was assessed in blinded
testing, and analyses were based on industry standard methods for assessment.
OUTCOMES: Maximum axial load; kink formation; horizontal stiffness; and
resistance to 3-point flexure testing were measured. RESULTS: At maximum
inflation, all 3 implants had similar performance. Differences appear to be most
affected by fill pressures. In fact, only the AMS LGX at less than maximum
inflation (LTMI) was unable to consistently withstand the roughly 0.9 kg (2 lbs)
of pressure for column load testing mimicking vaginal intromission. The Coloplast
Titan showed slightly better rigidity than the AMS LGX and CX devices in
horizontal load testing, and, with 3-point flexure testing, the CX showed the
best rigidity in the shortest phallus (A). Overall, the Titan showed slightly
better rigidity in the longest phallus (C) and the phallus with mild Peyronie's
disease (B). CLINICAL TRANSLATIONS: Penile implants with circumferential
expansion had higher rigidity on biomechanical testing and should be considered
in a patient's decision during selection of a penile implant. STRENGTHS AND
LIMITATIONS: Strengths include blinding of the biomechanical testing and
analyses, surgical procedures performed by a highly experienced surgeon, and that
this is the "closest to" in vivo evaluation (inside the tunica albuginea) of
penile implant function and properties to date. Weaknesses are that this study
was performed in cadavers and not in live patients. It also has a small sample
size, including the use of only 3 cadavers, and there was no correlation of
performance to patient satisfaction. CONCLUSION: The results of this study
support the conclusion that all devices are capable of functionally restoring
erectile capacity. However, we observed that, in general, the 2 circumferentially
expanding penile prosthesis showed greater resistance in biomechanical testing
when compared with longitudinal and circumferential expanding devices. This
should be considered as a guide during device selection for a patient undergoing
penile prosthesis. Wallen JJ, Barrera EV, Ge L, et al. Biomechanical Comparison
of Inflatable Penile Implants: A Cadaveric Pilot Study. J Sex Med 2018;15:1034
1040.
PMID- 29960630
TI - The Changes of MicroRNA Expression in the Corpus Cavernosum of a Rat Model With
Cavernous Nerve Injury.
AB - BACKGROUND: MicroRNAs (miRs) were found to be dysregulated in erectile
dysfunction (ED) related to aging, type 2 diabetes mellitus, and vasculogenic
abnormalities. However, miR expression in ED after radical prostatectomy (RP) is
not known. AIM: To detect abnormal miR expression in post-RP ED and analyze
target genes and pathways. METHODS: 16 Sprague Dawley rats were divided into
bilateral cavernous nerve crush (BCNC) and control groups. 4 weeks after surgery,
erectile function and histological change in the corpus cavernosum were
evaluated. Total RNA from 3 rats from each group was isolated and processed to
analyze the miR expression profiling by RNA sequencing. The top 10 up-regulated
miR profiles were chosen directly and further validated in another 5 rats per
each group by quantitative real-time polymerase chain (PCR) reaction. The target
genes were predicted by online databases, including: TargetScan, mirwalk,
miRanda, miRDB, and DIANA. The enrichment analysis of gene ontology-term analysis
and Kyoto Encyclopedia of Genes and Genomes were performed by DAVID database.
OUTCOMES: Intra-cavernosal pressure, mean arterial pressure, smooth muscle
content, and miR expression were measured. RESULTS: Compared to the control
group, the BCNC group had decreased intra-cavernosal/mean arterial pressure ratio
and smooth muscle marker (alpha-smooth muscle actin). The sequence results showed
that 124 miR expression dysregulated in the BCNC group, in which 122 miR
expression were up-regulated. Of the 122 miRs, 21 miR expressions were increased
above 2-fold. Among the top 10 up-regulated miRs, 4 miRs (miR-101a, miR-138, miR
338, and miR-142) levels were finally validated for over-expression by
quantitative (PCR) reaction. The gene ontology analysis results showed that these
4 miRs could regulate the processes of cell apoptosis, fibrosis, endothelium, and
smooth muscle cells function. The Kyoto Encyclopedia of Genes and Genomes pathway
analysis showed the target genes were involved in 7 pathways related to ED.
CLINICAL TRANSLATION: Our findings provide novel insights into post-RP ED that
may stimulate further studies to develop miR targeted therapy or damage detection
for ED. STRENGTHS & LIMITATIONS: To our knowledge, this is the first study to
identify the miR profiling and function in the BCNC rat model. The rat model
might not represent the human condition and the miR was only detected at 1
period. Besides that, there is a high probability of false positives for RNA
sequence results. CONCLUSION: 4 dysregulated miRs were found in the BCNC rat
model, which may be related to post-RP ED by regulating apoptosis, fibrosis,
endothelial, and smooth muscle cells. Liu C, Cao Y, Ko TC, et al. The Changes of
MicroRNA Expression in the Corpus Cavernosum of a Rat Model With Cavernous Nerve
Injury. J Sex Med 2018;15:958-965.
PMID- 29960631
TI - Ejaculatory Disorders in Men With Urethral Stricture and Impact of Urethroplasty
on the Ejaculatory Function: A Systematic Review.
AB - BACKGROUND: Urethral stricture may disturb both micturition and semen emission.
Urethroplasty, despite the restoration of a proper urethral patency, may not
eliminate the accompanying ejaculatory dysfunction (EjD). AIM: To investigate the
relationship among urethral stricture, urethroplasty, and ejaculatory function.
METHODS: For the systematic review, the authors followed the Preferred Reporting
Items for Systematic Reviews and Meta-Analysis statement. Internet-based
bibliographic databases (PubMed and Scopus) were searched to access studies that
examined the influence of urethral stricture and urethroplasty on ejaculatory
function. OUTCOMES: EjD accompanying urethral stricture, before and after
urethroplasty, was evaluated. RESULTS: 20 Studies were included in the final
analysis. In total, these studies comprised a population of 1,913 patients, aged
between 11-86 years, 1,823 with an anterior urethral stricture and 90 with a
posterior one. No randomized trials regarding the topic were found. Patients with
urethral stricture typically report poor force of ejaculation, reduced
ejaculatory volume, reduced pleasure, or complete failure to ejaculate. The
prevalence of pre-operative disorders depends on patients' age and is more severe
in the older population. The pre-operative stricture length, location, and type
of surgery have no statistically significant influence on post-operative EjD. In
some patients, despite a successful urethral reconstruction, problems with
ejaculation persist. The improvement in ejaculation after urethroplasty is
observed only in younger men. The available data are inconclusive whether the
separation of the bulbospongiosus muscle during urethroplasty impairs its later
functionality. CLINICAL IMPLICATIONS: Analyzing the available literature on the
subject, this review provides knowledge about the possible influence of
urethroplasty on ejaculatory function, which may be useful both in the pre
operative patient consultation and in the choice of treatment method. STRENGTHS &
LIMITATIONS: The evidence is sufficient to determine effects on health outcomes.
However, the strength of evidence is limited by the lack of randomized trials and
differences in terms of methodology and analyzed populations, preclusive of
conducting the meta-analysis. CONCLUSION: It has not been unequivocally
determined which factors related to the stricture or surgery are decisive for
post-operative ejaculatory function. The improvement in ejaculation after
urethroplasty is observed only in younger men. Kaluzny A, Gibas A, Matuszewski M.
Ejaculatory Disorders in Men With Urethral Stricture and Impact of Urethroplasty
on the Ejaculatory Function: A Systematic Review. J Sex Med 2018;15:974-981.
PMID- 29960632
TI - The Hemodynamic Effects of Intracavernosal Phenylephrine for the Treatment of
Ischemic Priapism.
AB - AIM: We sought to evaluate whether the administration of phenylephrine (PE) at
concentrations higher than those described in guidelines resulted in any
significant changes in vital signs or impacted outcomes. METHODS: After receiving
institutional review board approval, we retrospectively reviewed the charts of
patients presenting to our emergency department between May 1, 2014, and August
15, 2016, using International Classification of Diseases, Ninth Edition and
Internation Classification of Disease, Tenth Edition diagnosis codes for
priapism. Treatment was reviewed, including corporal aspiration/irrigation,
injection of PE, and shunt procedures. Vital signs were compared before and after
treatment with PE. Baseline variables were explored with categorical data
analysis (chi-squared tests, t-tests, and Mann-Whitney nonparametric tests).
Where feasible, linear regression was used to evaluate outcomes. MAIN OUTCOME
MEASURE: Detumescence and changes in blood pressure and heart rate. RESULTS: We
identified 74 different patient encounters of acute priapism. The median age was
36.5 years (interquartile range [IQR] = 27-47), and the median time to
presentation was 5.4 hours (IQR = 4.0-9.6). 62 percent of cases were due to drug
induced priapism. In 58 (74%) encounters, patients received PE. The median dose
of PE given was 1000 MUg (IQR 500-2,000). Univariate regression found no
association between PE dose and change in patient heart rate or blood pressure. A
statistically significant decrease in heart rate (HR) (-4.2 BPM), systolic blood
pressure (BP) (-1.8 mm Hg), and diastolic BP (-5.4 mm Hg) was noted. Fifty-three
of 58 (91%) patients receiving PE experienced detumescence at the bedside, 2
required shunting in operating room, and 3 refused treatment and left against
medical advice. No adverse events occurred. CONCLUSION: We frequently treat
patients with high doses of PE and seldom notice adverse effects, typically
resulting in resolution of priapism without any additional procedures. Careful
administration of high doses of intracavernosal PE in patients presenting with
priapism does not appear to significantly affect heart rate or blood pressure and
may help prevent further ischemic damage and achieve detumescence effectively and
efficiently. Sidhu AS, Wayne GF, Kim BJ, et al. The hemodynamic effects of
intracavernosal phenylephrine for the treatment of ischemic priapism. J Sex Med
2018;15:990-996.
PMID- 29960634
TI - Congratulations to APIC award winners.
PMID- 29960633
TI - Validity and Clinically Meaningful Changes in the Psychosexual Daily
Questionnaire and Derogatis Interview for Sexual Function Assessment: Results
From the Testosterone Trials.
AB - BACKGROUND: Limited information is available on the performance characteristics
of 2 questionnaires commonly used in clinical research, the Psychosexual Daily
Questionnaire (PDQ) and the Derogatis Interview for Sexual Function (DISF)-II
Assessment, especially in older men with low testosterone (T) and impaired sexual
function. AIM: To determine reliability of PDQ and DISF-II by assessing the
correlation within and between domains in the questionnaires and to define
clinically meaningful changes in sexual activity (PDQ question 4 [Q4]) and desire
(DISF-II sexual desire domain [SDD]) domains. METHODS: Data from 470 men
participating in the T Trials were used to calculate Spearman correlation
coefficients of individual items and total score among questionnaires to
determine convergent and construct validity. Clinically meaningful changes for
sexual desire and activity were determined by randomly dividing the sample into
training and validation sets. Anchor- and distribution-based clinically
meaningful change criteria were defined in the training set, and selected changes
were evaluated in the validation set. OUTCOMES: Validity of the PDQ and DISF-II
and clinically meaningful changes in sexual desire and activity were determined
in older men in T Trials. RESULTS: Moderate to strong correlations were shown
within and between domains from different questionnaires. Using Patient Global
Impression of Change as an anchor, clinically meaningful change in PDQ sexual
activity was >=0.6, and in DISF-SDD was >=5.0. Applying these change cut-points
to the validation set, a greater proportion of T-treated men achieved clinically
meaningful improvement in their sexual desire and activity compared to placebo
treated men. CLINICAL IMPLICATIONS: The PDQ-Q4 and DISF-II-SDD can be used to
reliably assess clinically meaningful changes in sexual activity and sexual
desire in hypogonadal men treated with T. STRENGTHS & LIMITATIONS: Strengths of
this study include a large sample size, long trial duration, and inclusion of men
with low libido and unequivocally low T levels. Limitations include using data
from a single study that enrolled only older hypogonadal men, and only 1 anchor
for both sexual desire and activity. CONCLUSION: Moderate to strong correlations
were demonstrated within and between different sexual domains of the PDQ and DISF
II confirming construct and convergent validity. Clinically meaningful
improvement in elderly hypogonadal men was change of >=0.6 score in the PDQ-Q4
and >=5.0 in the DISF-SDD. Improvements in sexual activity and desire in the T
Trials were modest but clinically meaningful. Wang C, Stephens-Shields AJ,
DeRogatis LR, et al. Validity and Clinically Meaningful Changes in the
Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function
Assessment: Results From the Testosterone Trials. J Sex Med 2018;15:997-1009.
PMID- 29960635
TI - Effect of Zishenpingchan granule prepared from Chinese medicinal substances on
the c-Jun N-terminal protein kinase pathway in micewith Parkinson's disease
induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
AB - OBJECTIVE: To investigate the regulatory mechanism of the c-Jun N-terminal
protein kinase (JNK)signaling pathway in substantia nigra (SN) dopaminergic
neurons inflammation and apoptosis, andthe neuroprotective effect of
Zishenpingchan granules in mice with Parkinson's disease (PD) inducedby 1-methyl
4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS: PD model mice were
established by intraperitoneally injecting MPTP. Sixty mice were dividedinto a
model group, Traditional Chinese Medicine (TCM) group and control group. The mice
ofthe TCM group were administered Zishenpingchan granules 7 days before PD
induction. Seven days afterPD induction, we examined locomotor activity, and
performed the rotarod test and swimming test,to evaluate limb movement function.
Furthermore, we used immunohistochemistry and western blottingto examine the
expression of tyrosine hydroxylase (TH), cyclooxygenase-2 (Cox-2), caspase-3 andp
JNK. The terminal deoxynucleotidyl transferase mediated dUTP nick end labeling
(TUNEL) methodwas used to examine neuron apoptosis in the SN. RESULTS: Compared
with the control group, the mean score of locomotor activity, rotarod test
andswimming test was significantly lower in the model group (P < 0.05); the TH
positive neuron expressionwas significantly decreased in the SN pars compacta
(SNpc); the protein expression levels of Cox-2,caspase-3 and p-JNK was obviously
increased; and the number of TUNEL-positive neurons in the SNwas increased (P <
0.01). Compared with the model group, the mean score of neurobehavioral tests
inthe TCM group was obviously higher, the loss of TH-positive neurons
ignificantly decreased, the proteinexpression levels of Cox-2, caspase-3 and p
JNK obviously decreased, and the number of TUNEL-positive neurons in the SN
clearly decreased (P < 0.01). CONCLUSION: The JNK pathway plays an important role
in the regulation of inflammation andapoptosis in nigral cells in PD mice. TCM
can suppress the over-activation of the JNK pathway in theSN, and alleviate the
inflammatory response in nigral cells and dopaminergic neuron apoptosis in PD
mice.
PMID- 29960636
TI - A march by any other name.
PMID- 29960637
TI - Lancisi's Sign: The Giant Venous Wave.
PMID- 29960638
TI - [Fluoropyrimidines cardiac toxicity: 5-fluorouracil, capecitabine, compound S-1
and trifluridine/tipiracil].
AB - The incidence of cardiac toxicity of 5-flurorouracil (5-FU) IV and capecitabine
varies from 1.2 to 18%. The physiopathology of this toxicity is still under
study, various hypotheses are mentioned. In the absence of identified
prophylactic treatment, reintroduction of this cytotoxic is at risk. A discussion
between oncologists and cardiologists is essential to estimate the balance
between benefit and risk and the careful reintroduction of treatment. An
alternative compound might be raltitrexed which is currently the treatment
recommended in case of intolerance to fluoropyrimidines. The compound S-1 does
not have any cardiac toxicity. Of a total of 2910 patients in phase II or III
studies, no grade III or IV cardiovascular events were reported. However, the
treatment is not reimbursed in France and therefore not available. The
trifluridine/tipiracil, for which approval from French authorities was obtained
in November 2016 for patients with metastatic colorectal cancer in progress
despite standard treatment lines, does not appear to have cardiac toxicity
according to studies published to date. The pivotal phase III study (RECOURSE),
that led to this marketing authorization, was performed in 800 patients with
metastatic colorectal cancer refractory and only one patient (less than 1% of
patients) treated with trifluridine/tipiracil presented an episode of cardiac
ischemia. Thus, trifluridine/tipiracil, which is well tolerated, could be an
alternative to raltitrexed for patients with cardiovascular history
contraindicating or discouraging the use of fluoropyrimidines.
PMID- 29960640
TI - Special Issue on Cell Biophysics.
PMID- 29960639
TI - [What role for the direct oral anticoagulants in oncology?]
PMID- 29960641
TI - Hypertension and Obstructive Sleep Apnea.
PMID- 29960642
TI - Authors' response.
PMID- 29960643
TI - Corrections and clarifications.
PMID- 29960644
TI - Authors' response.
PMID- 29960645
TI - Concerns about NSAIDs.
PMID- 29960646
TI - Systematic reviews and meta-analyses in minimally invasive surgery.
PMID- 29960647
TI - Rising to the challenge of fragility fractures.
PMID- 29960648
TI - Surgical team workload comparison for 4-port and single-port laparoscopic
cholecystectomy procedures.
AB - Advanced minimally invasive procedures may cause postural constraints and
increased workload and stress for providers. This study compared workload and
stress across surgical team roles for 48 laparoscopic cholecystectomies (4-port
vs single-port) using a task load index (NASA-TLX), a procedural difficulty
question, and salivary stress hormones. Statistical analyses were performed based
on the presence intra-cluster correlation within team roles, at alpha=0.05. The
single-port technique resulted in an 89% increase in physical workload for the
surgeon and 63% increase for the assistant (both p<0.05). The surgeon had
significantly higher salivary stress hormones during single-port surgeries. The
degree of procedural difficulty was positively correlated between the surgeon and
most roles: resident (r=0.67), assistant (r=0.81), and technician (r=0.81). There
was a statistically significant positive correlation between the surgeon and
assistant for all selfreported workload measures (p<0.05). The single-port
technique requires further improvement to balance surgical team workload for
optimal patient safety and satisfaction.
PMID- 29960649
TI - Increasing the reliability and reproducibility of aquatic ecotoxicology: Learn
lessons from aquaculture research.
AB - Regulatory ecotoxicology highly relies on aquatic toxicity studies carried out
under controlled conditions. Researchers recently expressed increasing concern
about their possible lack of repeatability/reproducibility in many cases. Poor
experimental designs, inappropriate statistics and lack of accurate reporting are
often pointed out. However, I believe that there is also insufficient attention
paid to the various experimental conditions under which fish studies are
conducted. These conditions encompass numerous factors (temperature, photoperiod,
food, stressors...) which modulate fish response to chemicals. Their effects are
poorly studied in ecotoxicology but have been investigated for decades in
aquaculture research. It is therefore proposed herein to consider experimental
ecotoxicology from an aquaculture perspective. An overview of modulating factors
and plausible associated experimental flaws is presented, with emphasis to fish
health, growth and reproduction which are the most common regulatory endpoints.
Photoperiod and temperature mainly determine growth/reproductive status for which
fish also have species and stage-specific nutritional requirements. Stressors,
sex ratio, density, water quality and factorial interactions may induce
experimental bias. Modulating factors can strongly limit findings applicability
and might explain the lack of reproducibility in some cases. Aquaculture
knowledge/experience can already allow avoiding some experimental flaws (e.g.,
stress) while further research is warranted for some other aspects (e.g.,
nutrition). Detailed reporting of fish husbandry and experimental conditions is
of utmost importance for study quality assessment.
PMID- 29960650
TI - Herd typologies based on multivariate analysis of biosecurity, productivity,
antimicrobial and vaccine use data from Danish sow herds.
AB - The use of antimicrobials in livestock constitutes an increasing global concern,
and many countries pursue approaches to reduce the amount used, particularly in
the pig production industry. The EU Commission has decided, due to environmental
concerns, to phase out use of zinc oxide in pigs by 2022. This poses an
additional challenge to efforts to reduce antimicrobial use (AMU) in European pig
production. The pig production sector needs further information about how to
comply with official AMU requirements without losing competitiveness. The most
efficient approaches are likely to involve a combination of multiple factors.
Therefore, the objective of this study was to explore multidimensional
associations between biosecurity, productivity, vaccination and AMU. A cross
sectional study was conducted using data from 160 Danish sow herds in 2014-2015.
Biosecurity data were collected through computer-assisted telephone interviews
using a pre-developed questionnaire (Biocheck.UGent(r)) supplemented with
additional country-specific questions and translated into Danish. Herd-specific
data, consisting of antimicrobial prescriptions, purchase of vaccines against
five endemic infections, herd health status and one productivity measure (i.e.
number of weaned piglets per sow per year) were extracted from various databases.
Factor analysis was conducted on a subset of the data from 152 herds with
sufficiently complete data. The identified factors were explained by evaluating
data from herds with extreme loadings on the respective factor. The results were
further discussed based on plots combining herd factor loadings on two factors at
a time. Four factors were selected based on the break-point in the scree-plot.
Factor 1 included herd type, herd size, and age of farm buildings. Factor 2
covered general biosecurity, including several internal and external biosecurity
measures. Factor 3 represented preventive measures implying specific focus on
avoiding introduction of ASF by foreign employees. Lastly, Factor 4 covered
vaccination status, specifically regarding vaccination against Mycoplasma
hyopneumoniae and Porcine Reproductive and Respiratory Syndrome virus. These
factors were used to group the 152 sow herds into herd typologies. Feasible
strategies aimed at improving health by reducing AMU without hampering animal
welfare were identified and discussed for each typology. AMU and productivity
correlated only weakly with other variables. This is probably due to limited
variability in both these variables in study herds, which might be attributed to
official restrictions on AMU, and a general high level of health and biosecurity
in Danish sow herds.
PMID- 29960651
TI - Hepatopulmonary syndrome.
PMID- 29960652
TI - Effect of high-intensity curing lights on the polymerization of bulk-fill
composites.
AB - OBJECTIVES: The purpose of this study was to investigate the effect of high
irradiance light-curing-units (LCUs) on the depth-of-cure (DoC) and degree-of
polymerization (DoP) of bulk-fill composites (BFCs). METHODS: The DoC of
composites (Beautifil-Bulk, SHOFU; Filtek-Bulk-Fill, 3M ESPE; Tetric-EvoCeram
Bulk-Fill, Ivoclar; Sonic-Fill-2, Kerr; Venus-Bulk-Fill, Heraeus; Z250, 3M-ESPE)
were measured according to ISO-4049 using high-irradiance LCUs (FlashMax-P3, CMS
Dental; SPEC3, Coltene) and conventional LCU (Paradigm, 3M-ESPE) for exposure
times: 3/9-s, 3/20-s, and 10/20-s respectively. Using FTIR, the DoP per composite
was measured at the bottom surface as a function of post-curing times for the
LCUs at the same exposure times. Data was analyzed with nonlinear regression and
ANOVA/Tukey. RESULTS: Significant differences in DoC were found amongst the LCUs
for the various exposure times. All BFCs failed to meet the DoC claimed by
manufacturers and failed to satisfy ISO-4049 with the high-irradiance LCUs with 3
s exposures. Standard irradiance and 20-s exposures outperformed all other
irradiance-exposure combinations for maximizing the DoC and DoP of BFCs. A
minimum of 15.3J/cm2 radiant exposure was required to achieve an adequate maximum
polymerization rate. Venus Bulk exhibited the highest DoC and DoP for any LCU
exposure-time combination. SIGNIFICANCE: Among the different combinations of BFCs
and LCUs, DoC and DoP were always increased with longer exposure time, but there
exists a theoretical radiant-exposure limit beyond which DoP or DoC remains
unchanged. However, high DoC or DoP are not always associated with one another.
Thus, the exposure-reciprocity law must be approached thoughtfully since
irradiance and exposure can independently affect DoP and DoC.
PMID- 29960653
TI - Hydration dependent mechanical performance of denture adhesive hydrogels.
AB - OBJECTIVE: Hydration in denture adhesives regulates the formation of complex
morphologies and mechanical function. Multiscale experimental approaches are
required to evaluate the impact of hydration on the inherent heterogeneity of
denture adhesive-based hydrogels at different length scales and the impact of
such phenomena on adhesion performance. METHODS: The morphology of hydrated
denture adhesives was examined via cryo-scanning electron microscopy (cryo-SEM).
The rheological and thermodynamic behaviour of bulk hydrated deture adhesives was
examined by rheology and differential scanning Calorimetry (DSC). The microscopic
mechanical properties of the denture adhesives were characterised by atomic force
microscopy (AFM) and compared to the properties measured at the macroscopic
scale. RESULTS: The rheological and mechanical properties of commerically
available denture adhesive hydrogels were found to be critically dependent on
both the formulation of the adhesives and their hydration level. Clear
progression of phase separation was observed in hydrated denture adhesives as
hydration increased and changed the mechanical properties of the adhesives at
multiple length scales. The adhesives displaying more heterogeneous structures,
which were associated with the presence of hydrophobic and organic compounds in
the formulation, exhibited more variable mechanical behaviour and weaker
rheological properties, but stronger adhesive properties. SIGNIFICANCE: Our
results are important in defining the relationships between hydrophilicity,
hydration, mechanical and adhesive properties of denture adhesives, allowing the
development of improved chemical formulations that control the fixation of
dentures.
PMID- 29960654
TI - A Female with Strange Movements.
PMID- 29960655
TI - Phacoemulsification of the rock-hard dense nuclear cataract: Options and
recommendations.
AB - We describe the essential steps in the successful phacoemulsification of the rock
hard, dense cataract. Appropriate and directed preoperative history, physical
examination, and diagnostics allow the surgeon to select the best incision,
anesthesia, and intended surgical technique for a given dense nuclear challenge.
Hard nucleus-specific approaches for hydrodissection, pupil management, and
zonular protection then allow the surgeon to approach the rock-hard nucleus with
maximum safety. Dense nuclear dismantling options are then discussed in detail
along with fluidic and power modulation considerations. Various specific
phacoemusification machine settings for rock-hard cataracts from the authors
representing several different phaco systems are then presented. The combination
of these steps and considerations allow a more successful dense cataract removal
and potential restoration of vision for patients. This paper represents the
collective experience and advice of the Challenging and Complex Cataract Surgery
Subcommittee.
PMID- 29960656
TI - Comparison of the effect of LASIK parameters on the percent tissue altered (1
dimensional metric) versus percent volume altered (3-dimensional metric).
AB - PURPOSE: To determine the theoretical volumes of flap and tissue ablation altered
during laser in situ keratomileusis (LASIK) correction of myopic refractive
errors. SETTING: Rothschild Foundation, Paris, France. DESIGN: Experimental
study. METHODS: The theoretical volumes of the flap and ablated corneal
lenticules for spherical myopic corrections were calculated by mathematical
approximations based on a simplified geometric model. These results were then
compared for various zone diameters, dioptric corrections, and the percentage of
the volumes altered (PVA) with the percentage of tissue altered (PTA). RESULTS:
The volume of the flap varied linearly with flap thickness and with the square of
the flap diameter. The volume of ablated corneal tissue was estimated to be
proportional to the magnitude of myopia treatment and to the 4th power of the
treatment diameter. For the same depth of ablation, the volume of tissue ablated
can vary significantly, depending on the magnitude of the correction and the
optical zone diameter. As a result, the PTA calculation is not predictive of the
actual PVA. CONCLUSIONS: The flap diameters and the laser correction were the
most important determinants of the PVA altered during LASIK surgery. New models
estimating the volume of the flap and corneal tissue might be necessary to
determine their influence on corneal biomechanical stability and each procedure's
outcome.
PMID- 29960657
TI - Angiography of ovarian and uterine vessels of the dog.
AB - A thorough knowledge about anastomoses between uterine and ovarian arteries could
have great impact in surgical interventions. The present study aimed to use an
angiographic procedure to show the vascular relationship between uterus and
ovaries, possible anastomoses between uterine arteries during pregnancy, blood
supply to gestational sacs, and the vascular pattern in the uterus of a bitch
with pyometra. Uteri from 6 dogs (3 non-pregnant, 2 pregnant, and one with a
pyometra uterus) were collected after ovariohysterectomy. A suspension of barium
sulfate was injected into the middle uterine artery and, dorso-ventral
radiographs were taken. In non-pregnant uteri, a contrast medium flowed into the
middle uterine artery and, after covering all of its branches, the medium entered
the ovarian parenchymal vessels. In addition, in the 35-day pregnant uteri, by
injecting the contrast medium into the middle uterine artery of one horn the
contralateral middle uterine artery received the media once the arteries of the
initial horn were filled. The results showed some anastomoses between arteries of
the two horns at this age of the pregnancy. The blood circulation of the
gestational sacs in each uterine horn started from the base of the horn and
continued to the apex. In conclusion, there are anastomoses between uterine and
ovarian arteries in non-pregnant, and between arteries of different uterine horns
in pregnant bitch.
PMID- 29960658
TI - Shortened daily photoperiod during the non-breeding season can improve the
reproductive performance of camel bulls (Camelus dromedarius).
AB - The effects of a shortened photoperiod on the reproductive performance and
hormones of mature dromedary camel bulls (Camelus dromedarius) were evaluated. A
group of 6 bulls were blindfolded to induce a daily photoperiod that was ~2.55 h
shorter than the natural day length (10.83L:13.17D), whereas 6 others served as
the control group. The trial started in June and continued for 10 weeks during
the non-breeding season. The reproductive performance of all animals was
evaluated weekly during this time and also during the breeding season, starting
in December and continuing for 10 weeks. Camel bulls in the treatment group
showed a significant (p < 0.05) increase in testicular volume, scrotal
circumference, sexual desire, reaction time, and mating ability scores, and serum
melatonin and testosterone concentrations, relative to the control group, during
the non-breeding season. In addition, sexual desire and reaction time and mating
ability scores were significantly (p < 0.05) higher in the treatment group than
in the control during the breeding season. There was no significant difference
between the treatment groups in both seasons and the control group in the
breeding season regarding semen volume, sperm cell concentration, total motility,
progressive motility, plasma membrane integrity, and viability. Shortening the
daily photoperiod by blindfolding can improve the reproductive performance of
dromedary camel bulls during the non-breeding season and the following breeding
season. This simple, inexpensive, and easily applicable method can enable
breeders to collect semen of acceptable quality during the non-breeding season.
PMID- 29960659
TI - Emergency medicine physicians' ability to predict hospital admission at the time
of triage.
AB - BACKGROUND: We seek to determine if experienced emergency medicine physicians can
accurately predict the likelihood of admission for patients at the time of
triage. Such predictions, if proven to be accurate, could decrease the time spent
in the ED for patients who will ultimately be admitted by hastening downstream
workflow. METHODS: This is a prospective cohort study of experienced physicians
at a large urban hospital. Physicians were asked to predict the likelihood of
admission for patients based only on information available in the EMR at the time
of triage. Physicians also predicted the service to which the patients would be
admitted. Physicians provided a confidence level of their prediction. Measures of
predictive accuracy were calculated, including sensitivity, specificity, and area
under the receiver operating characteristic curve. RESULTS: 35 physicians
evaluated 398 patient charts and made predictions. Sensitivity of determining
admission for the entire cohort was 51.8%. The specificity was 89.1%. For those
predictions made with a confidence level of >90%, sensitivity was 61.5% and
specificity was 95.7%. Among physicians correctly predicting admission, the
admitting service was predicted accurately 88.6% of the time. CONCLUSION:
Physicians performed poorly at predicting which patients would be admitted at the
time of triage, even when they were confident in their predictions. Conversely,
physicians accurately predicted who would be discharged. Physicians predicted
with reasonable accuracy the service to which patients were ultimately admitted.
More research and operational assessment needs to be performed to determine if
these predictions can help improve ED efficiency.
PMID- 29960660
TI - Emergency department utilization by a jail population.
AB - BACKGROUND: Incarcerated individuals represent a significant proportion of the US
population and face unique healthcare challenges. Scarce articles have been
published about emergency department (ED) care of these patients. We studied the
ED visits from one urban jail to better describe this population. METHODS: A
cohort study design was used, identifying patients who were sent to the ED from a
city jail in 2015. Demographics, triage information, length of stay, number of
studies, billing codes, diagnoses, and disposition data were collected. These
were compared to the overall ED patient population in the same year. RESULTS: 868
ED visits by jail patients occurred, representing 1.3% of the ED census. Compared
to the general population, incarcerated patients were younger (32.1 years vs.
44.0 years, p < .01), healthier based on Elixhauser comorbidity scores (0.71 vs.
0.98, p < .01), and had lower admission rates (11.29% vs. 21.54%, p < .01). An
abnormal vital sign was noted in 25% of incarcerated patients. Laboratory (61%
vs. 57%, p < .02) and radiologic (63% vs 45%, p < .001) testing was more frequent
for inmates and length of stay was longer (271 vs. 225 min, p < .01). CONCLUSION:
ED visits from jail were common, involving a relatively young and healthy
population with a low incidence of abnormal vital signs and admission. Given the
high costs associated with ED care and the medical resources available at some
jails, further study should evaluate if increased jail medical capabilities could
improve care and decrease costs by decreasing ED visits.
PMID- 29960662
TI - Comparison of Frequency of Silent Cerebral Infarction After Coronary Angiography
and Stenting With Transradial Versus Transfemoral Approaches.
AB - Silent cerebral infarction (SCI) can be seen after coronary procedures. We
investigated whether vascular access sites have an impact on the risk of SCI. A
total of 255 consecutive patients who underwent diagnostic or interventional
coronary procedures through transfemoral (n = 126 patients) or transradial (n =
129 patients) approach were evaluated. Neuron-specific enolase (NSE) levels were
studied before and 12 hours after the procedure. Elevation of greater than 12
ng/ml was considered as SCI. Patients were mainly men (60%) with a mean age of 62
years. SCI was observed in 74 of 255 patients (29%). It was significantly more
prevalent among transradial group. Elevation of NSE was observed in 36% of
transradial group (n = 47) and 21% of the transfemoral group (n = 27) (p =
0.008). Patients with SCI were more likely to have male sexuality,
hyperlipidemia, history of smoking, and previous myocardial infarction.
Multivariate analysis demonstrated that patients who underwent coronary
procedures through transradial approach were 2.1 times more likely to have an SCI
than patients with transfemoral approach (95% confidence interval [CI] 1.205 to
3.666; p = 0.008). Other independent predictors of NSE elevation were previous
myocardial infarction (odds ratio 8.6; 95% CI 4.209 to 17.572; p <0.001) and
smoking history (odds ratio 7.251; 95% CI 3.855 to 13.639; p <0.001). The present
study suggests that transradial coronary procedures carry higher risk of SCI when
compared with transfemoral route.
PMID- 29960661
TI - Hospital Complications and Causes of 90-Day Readmissions After Implantation of
Left Ventricular Assist Devices.
AB - Left ventricular assist devices (LVADs) have emerged as an attractive option in
patients with advance heart failure. Nationwide readmission database 2013 to 2014
was utilized to identify LVAD recipients using ICD-9 procedure code 37.66. The
primary outcome was 90-day readmission. Readmission causes were identified using
ICD-9 codes in primary diagnosis field. The secondary outcomes were LVAD
associated with hospital complications. Hierarchic 2-level logistic models were
used to evaluate study outcomes. We identified 4,693 LVAD recipients (mean age 57
years, 76.2% males). Of which 53.9% were readmitted in first 90 days of
discharge. Cardiac causes (33.3%), bleeding (21.3%), and infections (12.4%) were
leading etiologies of 90-day readmissions. Significant predictors (odds ratio,
95% confidence interval, p value) of readmission were disposition to nursing
facilities (1.33, 1.09 to 1.63, p = 0.01) and longer length of stay (1.01, 1.00
to 1.01, p <0.01). Although private insurance (0.75, 0.66 to 0.86, p <0.01), and
self-pay (0.58, 0.42 to 0.81, p <0.01) predicted lower readmissions. Cardiac
complications (36.3%), major bleeding (29.8%), and postoperative infections
(10.4%) were most common LVAD-related complications. In conclusion, high early
readmission rate was observed among LVAD recipients with Cardiac complications,
bleeding complications, and infections were driving force for major complications
and most of readmissions.
PMID- 29960663
TI - Primary Ventricular Fibrillation in the Primary Percutaneous Coronary
Intervention ST-Segment Elevation Myocardial Infarction Era (from the "Codi IAM"
Multicenter Registry).
AB - Primary ventricular fibrillation (PVF) is a dreadful complication of ST segment
elevation myocardial infarction (STEMI). Scarce data are available regarding PVF
prognosis since primary percutaneous coronary intervention (PPCI) became routine
practice in STEMI. Our aim was to compare 30-day and 1-year mortality for
patients with and without PVF (including out-of-hospital and in-hospital PVF)
within a regional registry of PPCI-treated STEMI patients. This prospective
multicenter registry included all consecutive STEMI patients treated with PPCI
from January 2010 to December 2014. Patients were classified as non-PVF or PVF,
with further subdivision into out-of-hospital and in-hospital PVF. We analyzed 30
day and 1-year all-cause mortality in groups. The registry included 10,965
patients. PVF occurred in 949 patients (8.65%), including 74.2% out-of-hospital
and 25.8% in-hospital PVF. Compared with the non-PVF group, PVF patients were
younger; less commonly diabetic; more frequently had anterior wall STEMI, higher
Killip-Kimball class, and left main disease; and showed significantly higher 24
hour (5.1% vs 1.1%), 30-day (18.5% vs 4.7%), and 1-year mortality (23.2% vs 7.9%)
(all p <0.001). Mortality did not differ in out-of-hospital versus in-hospital
PVF. After multivariable adjustment, PVF remained associated with all-cause 30
day (2.32, 95% CI: 1.91 to 2.82, p <0.001) and 1-year (HR: 1.59, 95% CI: 1.13 to
2.24, p = 0.008) mortality. In conclusion, we present the largest registry of PVF
patients in the era of routine PPCI in STEMI. Although overall STEMI mortality
has declined, PVF emerged as a predictor of both 30-day and 1-year mortality.
These data warrant prospective validation and proper identification and
protection of high-risk patients.
PMID- 29960664
TI - Comparison of Causes and Associated Costs of 30-Day Readmission of Transcatheter
Implantation Versus Surgical Aortic Valve Replacement in the United States (A
National Readmission Database Study).
AB - Our current knowledge about comparative differences in 30-day readmissions and
the impact of readmissions on overall costs after transcatheter aortic valve
implantation (TAVI) and surgical aortic valve replacement (SAVR) is largely
derived from clinical trials. The objectives of this study were to compare
readmissions and costs for TAVI and SAVR in a nationally representative
population-based sample. The Healthcare Cost and Utilization Project's National
Readmission Database was used for the study. Hierarchical multivariable
regression analyses were used to examine differences in the propensity score 1:1
matched cohort. The matched cohort included 4,682 patients who survived index
procedures done from January through November 2013. Compared with SAVR, the rate
of 30-day readmission was not significantly different for endovascular TAVI (16%
vs 18%; p = 0.19); and was higher for the transapical TAVI (22% vs 17%; p <0.01)
group. The 30-day cumulative costs were higher for the 2 endovascular TAVI
($51,025 vs $46,228; p = 0.03) and transapical TAVI ($59,575 vs $45,792; p
<0.01). In multivariable analyses, the risk of 30-day readmission was similar for
endovascular TAVI (odds ratio [OR] 0.93; 95% confidence interval [CI] 0.78 to
1.12) and was 27% higher for transapical TAVI (OR 1.27; 95% CI 1.02 to 1.57).
Cumulative costs (index plus readmission costs) were 13% (beta 0.13; 95% CI 0.10
to 0.15) and 19% (beta 0.19; 95% CI 0.16 to 0.23) higher for the endovascular
TAVI and transapical TAVI, respectively. In conclusion, the rate of readmissions
was similar for endovascular TAVI and SAVR but the costs were 26% higher for TAVI
than for SAVR.
PMID- 29960665
TI - Socioeconomic Disadvantage and Days at Home After Hospital Discharge of Patients
with Heart Failure.
AB - The risk of heart failure (HF) readmission may be reduced by disease management
programs, but the resource-intensive nature of these requires targeting to the
greatest need. As socioeconomic status (SES) is related to other health outcomes,
we sought whether regional markers of SES were associated with days at home
(alive and out of hospital) after discharge. This study used statewide data of
1,391 HF patients who had their first ever HF admission to a public hospital in
Tasmania (Australia) during 2009 to 2012. Measurements of residential SES
included four indexes and a remoteness index generated by the Australian Bureau
of Statistics. The primary outcome was days at home. Secondary outcomes included
30- and 90-day readmission or death, number of readmissions, and days to first
readmission. Our HF patients had a median of 352 days at home [interquartile
range 167, 361]. All four SES indexes and the remoteness index (p <0.001) were
adversely associated with days at home, independent of other clinical and
nonclinical factors. Findings for readmission at 30 and 90 days of discharge were
inconsistent; the index of Relative Socioeconomic Advantage and Disadvantage (but
not other SES indexes) was independently associated with 30-day readmission (odds
ratio 1.58, p = 0.008) and remoteness index was significantly associated with 90
day readmission (odds ratio = 1.99, p = 0.009). Analyzing days to first
readmission did not show any significant differences among categories of SES (log
rank test p = 0.81) or remoteness index (log-rank test p = 0.47). Thus,
residential SES is associated with adverse outcome in HF, and might be useful in
planning services to reduce HF readmission.
PMID- 29960666
TI - Mechanical Thrombectomy: Emerging Technologies and Techniques.
AB - BACKGROUND: The treatment of acute ischemic stroke due to large vessel occlusion
(LVO) has revolutionized in the last decade. We sought to compile the most
relevant literature published about the evolution in treating this disabling and
fatal disease. METHODS: A literature review of recent studies describing early
treatment options like intravenous tissue plasminogen activator to the latest
mechanical thrombectomy (MT) techniques was performed. We described in a
chronological order the evolution of LVO treatment. RESULTS: Recanalization rates
with newer techniques and MT devices approach a 90% of effectiveness. Timely
interventions have also resulted in better clinical outcomes with approximately
50% of patient achieving functional independence at 90 days. At least 14 new
third generation thrombectomy devices are currently being evaluated in in vitro
and clinical studies. CONCLUSIONS: The treatment of LVO with MT is feasible and
safe. MT is standard of care in treating acute ischemic stroke due to LVO.
PMID- 29960667
TI - Homocysteine is Associated with Exaggerated Morning Blood Pressure Surge in
Patients with Acute Ischemic Stroke.
AB - BACKGROUND: Considerable researches suggest that high level of homocysteine (Hcy)
is associated with the risk of ischemic stroke. Ambulatory blood pressure
monitoring (ABPM) parameters have also been confirmed associated with cardio
cerebrovascular events. However, the relationship between Hcy and ABPM parameters
remains unclear in patients with acute ischemic stroke. In this study, we aim to
investigate the association between Hcy level and ABPM parameters in patients
with acute ischemic stroke. METHODS: We enrolled 60 patients with acute ischemic
stroke who received ABPM. We calculated ABPM parameters like morning blood
pressure surge (MBPS), ambulatory arterial stiffness index, blood pressure
variability, and night dipping patterns. RESULTS: Multivariate logistic
regression analysis indicated that patients in the top quartile of Hcy level
tended to have a higher level of prewaking and sleep-trough MBPS compared with
patients in the lower 3 quartiles after adjusted for age and gender (P = .028 and
P = .030, respectively). When treating Hcy as a continuous variable, the linear
regression showed the association between Hcy level and both MBPS parameters
remained significant (prewaking MBPS, r = .356, P = .022; sleep-trough MBPS, r =
.365, P = .017, respectively). However, there is no association between Hcy level
and ambulatory arterial stiffness index, blood pressure variability or night
dipping patterns (P = .635, P = .348 and P = .127 respectively). CONCLUSIONS:
There is a relationship between the 2 major cerebrovascular risk factors: MBPS
and Hcy.
PMID- 29960669
TI - Immuno-metabolic changes in herpes virus infection.
AB - Recent evidences indicate that change in cellular metabolic pathways can alter
immune response and function of the host; emphasizing the role of metabolome in
health and diseases. Human Herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2)
causes diseases from asymptomatic to highly prevalent oral and genital herpes,
recurrent blisters or neurological complications. Immune responses against HSV
are complex with delicate interplay between innate signaling pathways and
adaptive immune responses. The innate response involves the induction of
protective IFN-1; while Natural Killer (NK) cells and plasmacytoid Dendritic
Cells (pDC) confer in vivo adaptive anti-HSV response along with humoral and
cellular components in controlling infection and latency. Metabolic changes lead
to up-/down-regulation of several cytokines and chemokines like IFN-gamma, IL-2,
IL-4, IL-10 and MIP1beta in HSV infection and recurrences. Recently, the viral
protein ICP0 has been identified as an attenuator of TLR signaling, that inhibit
innate responses to HSV. This review will summarize the role of metabolome in
innate and adaptive effectors in infection, pathogenesis and immune control of
HSV, highlighting the delicate interplay between the metabolic changes and
immunity.
PMID- 29960668
TI - Depression and Risk of Alzheimer Dementia: A Longitudinal Analysis to Determine
Predictors of Increased Risk among Older Adults with Depression.
AB - OBJECTIVE: Older adults with depression are at increased risk of Alzheimer
dementia, but predictors of increased risk remain incompletely understood. We aim
to identify characteristics of older adults with depression most at risk of
progressing to Alzheimer dementia. Identification of high-risk subgroups could
facilitate future interventional strategies to reduce risk of Alzheimer dementia
in older adults with depression. METHODS: Using data from the National
Alzheimer's Coordinating Center, 1,965 participants with clinically defined
depression and mild cognitive impairment at baseline were followed until
development of Alzheimer dementia or loss to follow-up. RESULTS: Seven hundred
and eighty (39.7%) developed Alzheimer dementia over a median follow-up duration
of 27 months. In survival analyses, age (hazard ratio [HR] 1.04, 95% 1.03-1.05),
baseline Mini-Mental State Exam (HR 0.85, 95% confidence interval 0.83-0.87),
amnestic subtype of mild cognitive impairment (HR 1.66, 95% 1.30-2.12), presence
of APOE4 allele (HR 1.99, 1.69-2.36), and presence of active depression within
the last two years (HR 1.44, 95% confidence interval 1.16-1.79) were all
independently associated with increased risk of Alzheimer dementia. Six hundred
and fifty-six (41.7%) participants with mild cognitive impairment and active
depression within the last two years developed Alzheimer dementia compared to 120
(31.6%) of those with a more remote history of depression. CONCLUSION: Older
adults with depression and mild cognitive impairment demonstrated a high rate of
progression to Alzheimer dementia over a relatively short duration of follow-up.
Individuals with a combination of mild cognitive impairment and recently active
depression are a particularly high-risk subgroup.
PMID- 29960670
TI - Clinical Predictors of Port Infections in Adult Patients with Hematologic
Malignancies.
AB - PURPOSE: To identify clinical predictors of port infections in adult patients
with hematologic malignancies. MATERIALS AND METHODS: A retrospective chart
review identified 223 adult patients (age >= 18 y) with hematologic malignancies,
including lymphoma (n = 163), leukemia (n = 49), and others (n = 11), who had a
port placed from 2012 to 2015. Early (< 30 d after port placement) and overall
port infections (bloodstream and site infections) were recorded. To elucidate
clinical predictors for early and overall port infections, proportional
subdistribution hazard regression (PSHREG) analyses were conducted with variables
including patients' demographics, medications used, laboratory data, and port
characteristics. RESULTS: Total duration of follow-up was 83,722 catheter-days
(median per patient, 274 catheter-days). Early and overall port infections were
identified in 8 (3.6%) and 26 (11.7%) patients, respectively. Early and overall
infection rates were 1.2 and 0.3 infections/1,000 catheter-days, respectively.
Backward stepwise multivariate PSHREG analyses identified hypoalbuminemia (< 3.5
mg/dL) at the time of port placement (hazard ratio = 5.03; 95% confidence
interval, 1.14-22.16; P = .03) and steroid use (> 30 d cumulatively during follow
up period) (hazard ratio = 3.41; 95% confidence interval, 1.55-7.47; P = .002) as
independent risk factors for early and overall port infections, respectively.
CONCLUSIONS: In adult patients with hematologic malignancies, hypoalbuminemia at
the time of port placement was a clinical predictor for early port infections,
whereas steroid use was a clinical predictor for overall port infections.
PMID- 29960672
TI - Townley's Chloroform Inhaler.
AB - While cataloguing the historical items in the Department of Anaesthesia,
Addenbrooke's Hospital, Cambridge, UK, we discovered an unusual chloroform
inhaler, which incorporated two air-inlet tubes in addition to its main
inspiratory valve as well as a funnel on one of its lateral walls. An
accompanying card stated that the device was thought to be a modification of
Snow's inhaler, by James Robinson. It had been found among some old instruments
in a General Practice in Huntingdon, Cambridgeshire, and had probably been
acquired by an early practitioner named Dr. Newton, who qualified in 1851 and
performed a lot of minor surgery in the practice. Using information published in
books, medical journals, instrument catalogues, and other sources available in
the public domain, we sought to confirm the identify of this inhaler and further
investigate its provenance. Soon after the introduction of chloroform anesthesia
in November 1847, James Robinson modified Snow's ether face-piece to produce an
ingenious device for administering the vapor of chloroform. However, Robinson's
inhaler did not include the air-inlet tubes, or funnels, which are an integral
feature of the device found in the Addenbrooke's collection. Following further
research, we formally identified our device to be of the type introduced by James
Townley in 1862 for use with his "Anodyne mixture." We describe Townley's
chloroform inhaler and provide an insight into the life and work of its inventor,
as well as Dr. Newton and his son, who may have used the apparatus in the
Cambridgeshire area.
PMID- 29960673
TI - Recent History of Publication-Based Academic Interest in General Anesthetics.
AB - PURPOSE: The aim of this study was to determine how interest in various general
anesthetics among the authors of academic publications changed over the past 50
years. METHODS: Publication-based academic interest were analyzed using specific
scientometric indices: popularity index (PI), top journal selectivity index
(TJSI), and index of change (IC). Terms used for searches were the names of drugs
belonging to two pharmacological classes of general anesthetics - inhaled and
intravenous. Only those that had a PI value > 2.0 during at least one of the 10
five-year periods, from 1967 to 2016, were selected. RESULTS: The PI, an index of
comparative popularity, reflects a consistent decline in academic interest over
time in both classes of general anesthetics. Over the past 25 years, the PI of
inhaled anesthetics decreased by 52 %, and that of intravenous anesthetics fell
by 32%. At the same time, the PI of anesthesia management increased by 167%.
Among individual anesthetics, the most impressive change was a profound decline
in halothane's PI, from 22.9 in 1972-1976 to 0.5 in 2012-2016. The interest in
halothane was gradually supplanted by that in new agents, initially by enflurane,
followed by isoflurane and finally, sevoflurane. The next meaningful change was
the gradual rise in sevoflurane's PI to surpass that of isoflurane. The most
dramatic change among the PIs of intravenous anesthetics was associated with the
introduction of propofol: an increase from 1.8 to its maximum of 13.6.
CONCLUSIONS: The study revealed a constant decline over time in academic interest
in the pharmacological basis of general anesthesia relative to all fields of
anesthesia combined.
PMID- 29960674
TI - The Perfect and Famous Anesthetic Known as Methyl in Boston in 1895.
AB - Extravagant claims were made for proprietary dental anesthetics in Boston, MA, in
the late 1800s. For instance, in 1883, Urial K. Mayo introduced an inhaled
Vegetable Anaesthetic comprised of nitrous oxide that had been uselessly
pretreated with botanical material. This misguided concept may have been inspired
by homeopathy, but it was also in line with the earlier false belief of Elton R.
Smilie, Charles T. Jackson, and William T.G. Morton that sulfuric ether could
volatilize opium at room temperature. In 1895, the Dental Methyl Company
advertised an agent they called Methyl, a supposedly perfect topical anesthetic
for painless dental extraction. The active ingredient was probably chloroform.
Anesthetic humbug did not cease in Boston on Ether Day of October 16, 1846.
PMID- 29960675
TI - Popular Literature as an Educational Aid for History of Anesthesia.
AB - INTRODUCTION: History of anesthesia can be learned through formal didactic
lectures, discussions, tours, audiovisual media, general anesthesia textbooks,
anesthesia history texts, and by popular literature. METHODS: We studied thirteen
books that describe events and advances related to the discovery and development
of modern anesthesia. Deliberately omitted were books that might be considered by
some to be textbooks, because our aim was to explore the genre of popular
literature. RESULTS: The books span the spectrum from introductory historical
narratives to comprehensive summaries, biographies, and scholarly works.
CONCLUSIONS: These books provide a varied perspective on various aspects of the
discovery of anesthesia, ranging from a quick read to scholarly work. If only one
book were to be recommended for the novice, we suggest Julie Fenster's historical
narrative, Ether Day.
PMID- 29960676
TI - Charles T. Jackson and William T.G. Morton Patented the "Ethereal Solution of
Opium" of Elton Romeo Smilie.
AB - The Jackson-Morton 1846 patent for surgical insensibility by means of sulphuric
ether states that opiates can be added to the ether and co-administered by
inhalation. The erroneous concept that ether could carry opiates in its vapor
phase at room temperature was proposed in Boston in 1846 by Elton Romeo Smilie
(1819-1889), who believed that the opiates were more important than the ether
vehicle.
PMID- 29960678
TI - From Dental to Mental Institutions: An American Dentist and a British
Psychiatrist Highlight Insanity Following Nitrous-Oxide Administration.
AB - In 1887, American dentist Samuel J. Hayes published reports associating
unoxygenated anesthetics with asphyxia and insanity, and then British
psychiatrist George H. Savage published a report of cases of insanity following
nitrous-oxide anesthesia in British journals.
PMID- 29960677
TI - A Nitrous-Oxide Pioneer Peddles His Own Dentifrice: "Dr Colton's Vegetable
Dentonic".
AB - During the latter half of the six-year long "Panic of 1873," nitrous-oxide
pioneer G.Q. Colton developed, advertised, and sold his dentifrice, "Dr Colton's
Vegetable Dentonic" to supplement his dental anesthetic enterprise.
PMID- 29960679
TI - The Use and Relevance of the Hippocratic Oath in 2015-a Survey of US Medical
Schools.
AB - INTRODUCTION: We determined the extent and context in which the Hippocratic or
other oaths are administered at accredited medical schools in the United States.
METHODS: An online survey was used to gather data about oath ceremonies at every
allopathic medical school in the US. RESULTS: Sixty-seven of 141 contacted
medical schools (48%) had medical students recite an oath. Fifty-nine (88% of
responding institutions) had students swear an oath more than once during medical
training and 30 (45%) used more than one oath. Responses show that 29 (43%)
schools used the classic Hippocratic Oath or a modified version of it, 29 (43%)
used oaths authored by students and/or faculty, and 28 (42%) used some other
oath. All reporting institutions (67, 100%) incorporated an oath into a White
Coat Ceremony (62, 92%), a ceremonial event where medical students are given
short white coats to be worn during clinical rotations, or Commencement (62,
93%). DISCUSSION: Oaths play a significant role in medical school ceremonies with
an unknown impact on shaping the medical ethics of student physicians. Although
sections of the Hippocratic Oath may seem outdated, its principles remain vastly
applicable to the ethical practice of modern medicine. On the contrary, we argue
that many features of the oath are more applicable than ever before to the modern
clinician. We believe that the Hippocratic Oath ought to remain a vital part of
today's medical education and clinical practice.
PMID- 29960680
TI - Multiparametric slice culture platform for the investigation of human cardiac
tissue physiology.
AB - Human cardiac slices have emerged as a promising model of the human heart for
scientific research and drug testing. Retaining the normal tissue architecture, a
multi-cell type environment, and the native extracellular matrix, human cardiac
slices faithfully replicate organ-level adult cardiac physiology. Previously, we
demonstrated that human cardiac tissue slices cultured for 24 h maintained normal
electrophysiology. In this project, we further optimized the organotypic culture
condition to maintain normal electrophysiology of the human cardiac slices for 4
days. The prolonged culture of human cardiac tissue slices demonstrated here
enables the study of chronic drug effects, gene therapies, and gene editing. To
achieve greater control of the culture environment, we have also developed an
automated, self-contained heart-on-a-chip system. The culture system supports
media circulation, oxygenation, temperature control, electrical stimulation, and
static mechanical loading. The culture parameters can be individually adjusted to
establish the optimal culture condition to achieve long-term culture and to
minimize tissue dedifferentiation. The development of the heart-on-a-chip
technology presented here further encourages the use of organotypic human cardiac
slices as a platform for pre-clinical drug testing and research in human cardiac
physiology.
PMID- 29960681
TI - [Mentalization based treatment (MBT) for borderline personality disorder among a
population of French-speaking patients].
AB - INTRODUCTION: Borderline Personality Disorder is a frequent disorder that is
challenging for therapists to treat due to the prevalence of self-damaging and
suicidal behaviours and interruptions of the therapeutic alliance, as well as a
poor response to psychotropic treatments. In recent years, several empirically
validated psychotherapeutic treatments have been developed, including
Mentalisation-Based Therapy, which is an integrative psychodynamic approach
created in Britain. Although numerous studies have showed Mentalisation-Based
Therapy to be an efficient treatment of Borderline Personality Disorder, its
specific components have yet to be assessed. Furthermore, there have been no
empirical studies conducted among groups of French-speaking patients. The purpose
of this study is twofold: To provide an initial assessment of the efficacy of the
mentalisation-based psycho-educational component, which is the first component of
any mentalisation-based therapy, and to provide the first assessment of this
approach among a population of French-speaking patients. METHOD: Over a three
month period, 14 Borderline Personality Disorder sufferers followed a psycho
educational Mentalisation-Based Therapy programme consisting of group sessions to
introduce patients to mentalisation and weekly individual interviews. Patients
filled in various question forms assessing, among others, the intensity of their
depression, their degree of hopelessness, their emotional regulation strategies,
and their reflective abilities. RESULTS: The psycho-educational component of
Mentalisation-Based Therapy is significantly associated with improved cognitive
emotional regulation, empathy and reflective abilities, and with a reduced sense
of hopelessness. The programme retention rate was of 71.4%. CONCLUSION: Despite
the small sample size and the short treatment period, these preliminary results
demonstrate the efficiency of the psycho-educational phase of Mentalisation-Based
Therapy, and in particular the positive effects of the treatment on depressive
symptomatology and self-regulation processes among patients with a Borderline
Personality Disorder diagnosis.
PMID- 29960682
TI - Decline of empathy among medical students: Dehumanization or useful coping
process?
AB - OBJECTIVES: Empathy is central in patient-physician interactions and
understanding its development is decisive for education. However, scientific
literatures report a striking decline of empathy among medical students during
their study course. Firstly, we aimed to replicate this result on a Belgian
population. Secondly, as well reported by literature, we expected higher empathy
scores for women. Lastly, as central, we expected higher empathy levels for
medical students than for "control" students (commercial students were used as a
control group: social interactions without a curing aspect) at the beginning of
their study course, suggesting that empathy drives students to select specific
education fields. METHODS: Through a cross-sectional design, we assessed students
from medical and commercial educations at different years of study with the Basic
Empathy Scale (N=1602). We compared: (1) empathy scores at different scholar
levels for both populations; (2) scores between men and women; (3) empathy scores
between medical and commercial students in their first year of study. RESULTS: As
expected, a significant empathy decline was displayed over time for medical
students; women reported significant higher empathy scores than men; and, in
their first year, medical students presented significant higher empathy scores
than commercials. CONCLUSIONS: Replicating the empathy decline on several student
populations is crucial, especially by using different tools. This decline is a
multi-factorial process that mainly reflects self-representation changes. The
empathy gender bias is a strong effect observed in several empathy-linked
phenomena. Finally, empathy is not only central but also drives students to
select specific education fields.
PMID- 29960683
TI - Psychometric properties of the Resilience Scale - 14 in a sample of college
students from France.
AB - INTRODUCTION: In recent years, the integration of resilience in several
psychological and medical studies underscores a need for resilience assessment
measures with robust psychometric properties. This study aimed to evaluate the
underlying structure of the French version of the Resilience Scale (RS-14), a
widely used measure to assess resilience both in general and clinical population.
METHOD: A sample of 2195 college students from France (18.68% of male; Mean
age=20.09 years old (+/-1.21) completed the RS-14, the Child and Youth Resilience
Measure, the Social Support Questionnaire and the Kessler Psychological Distress
Scale. EFA with parallel analysis was conducted to assess the factorial structure
of the RS-14 while CFA was performed to investigate the goodness-of-fit. Internal
consistency, concurrent and convergent validity were evaluated. RESULTS: A one
dimensional-factorial-solution emerged from the EFA, its goodness-of-fit was
adequate and it presented good internal consistency. As expected, the RS-14 score
correlated positively to the CYRM and SSQ scores and negatively to the
psychological distress score, supporting the validity of the scale. CONCLUSION:
The one-dimensional-factor corroborates the initial and many languages versions
of the RS-14. The results showed that the French version of the RS-14 presents
adequate psychometric properties and that is a reliable and valid scale in
evaluating resilience.
PMID- 29960671
TI - Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098
Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis
(ENIGMA) Consortium.
AB - BACKGROUND: The profile of cortical neuroanatomical abnormalities in
schizophrenia is not fully understood, despite hundreds of published structural
brain imaging studies. This study presents the first meta-analysis of cortical
thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA
(Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working
Group. METHODS: The study included data from 4474 individuals with schizophrenia
(mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers
(mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized
methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers,
individuals with schizophrenia have widespread thinner cortex (left/right
hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right
hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in
frontal and temporal lobe regions. Regional group differences in cortical
thickness remained significant when statistically controlling for global cortical
thickness, suggesting regional specificity. In contrast, effects for cortical
surface area appear global. Case-control, negative, cortical thickness effect
sizes were two to three times larger in individuals receiving antipsychotic
medication relative to unmedicated individuals. Negative correlations between age
and bilateral temporal pole thickness were stronger in individuals with
schizophrenia than in healthy volunteers. Regional cortical thickness showed
significant negative correlations with normalized medication dose, symptom
severity, and duration of illness and positive correlations with age at onset.
CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can
achieve robust findings in clinical neuroscience studies; also, medication
effects should be taken into account in future genetic association studies of
cortical thickness in schizophrenia.
PMID- 29960684
TI - Adjuvant postoperative high-dose radiotherapy for atypical and malignant
meningioma: A phase-II parallel non-randomized and observation study (EORTC 22042
26042).
AB - PURPOSE: The therapeutic strategy for non-benign meningiomas is controversial.
The objective of this study was to prospectively investigate the impact of high
dose radiation therapy (RT) on the progression-free survival (PFS) rate at 3
years in WHO grade II and III meningioma patients. MATERIALS AND METHODS: In this
multi-cohorts non-randomized phase II and observational study, non-benign
meningioma patients were treated according to their WHO grade and Simpson's
grade. Patients with atypical meningioma (WHO grade II) and Simpson's grade 1-3
[Arm 1] entered the non-randomized phase II study designed to show a 3-year PFS >
70% (primary endpoint). All other patients entered the 3 observational cohorts:
WHO grade II Simpson grade 4-5 [Arm 2] and Grade III Simpson grade 1-3 or 4-5
[Arm 3&4] in which few patients were expected. RESULTS: Between 02/2008 and
06/2013, 78 patients were enrolled into the study. This report focuses on the 56
(median age, 54 years) eligible patients with WHO grade II Simpson's grade 1-3
meningioma who received RT (60 Gy). At a median follow up of 5.1 years, the
estimated 3-year PFS is 88.7%, hence significantly greater than 70%. Eight
(14.3%) treatment failures were observed. The 3-year overall survival was 98.2%.
The rate of late signs and symptoms grade 3 or more was 14.3%. CONCLUSIONS: These
data show that 3-year PFS for WHO grade II meningioma patients undergoing a
complete resection (Simpson I-III) is superior to 70% when treated with high-dose
(60 Gy) RT.
PMID- 29960685
TI - Stereotactic radiosurgery and immunotherapy in melanoma brain metastases:
Patterns of care and treatment outcomes.
AB - PURPOSE: Preclinical studies have suggested that radiation therapy (RT) enhances
antitumor immune response and can act synergistically when administered with
immunotherapy. However, this effect in melanoma brain metastasis is not well
studied. We aim to explore the clinical effect of combining RT and immunotherapy
in patients with melanoma brain metastasis (MBM). MATERIALS AND METHODS: Patients
with MBM between 2011 and 2013 were obtained from the National Cancer Database.
Patients who did not have identifiable sites of metastasis and who did not
receive RT for the treatment of their MBM were excluded. Patients were separated
into cohorts that received immunotherapy versus patients who did not. Univariable
and multivariable analyses were performed using Cox model to determine predictors
of OS. Kaplan-Meier method was used to compare OS. Univariable and multivariable
analyses using logistic regression model were used to determine the factors
predictive for the use of immunotherapy. Propensity score analysis was used to
account for differences in baseline patient characteristics between the RT and RT
+ immunotherapy groups. Significance was defined as a P value <= 0.05. RESULTS: A
total of 1104 patients were identified: 912 received RT alone and 192 received RT
plus immunotherapy. The median follow-up time was 6.4 (0.1-56.8) months. Patients
with extracranial disease (OR 1.603, 95% CI 1.146-2.243, P = 0.006), and patients
receiving SRS (OR 1.955, 95% CI 1.410-2.711, P < 0.001) as compared to WBRT, had
a higher likelihood of being treated with immunotherapy. The utilization of
immunotherapy had nearly doubled between 2011 and 2013 (12.9-22.8%). On
multivariable analysis, factors associated with superior OS were younger age,
lower medical comorbidities, lack of extracranial disease, and treatment with
immunotherapy and SRS. The median OS was 11.1 (8.9-13.4) months in RT plus
immunotherapy vs. 6.2 (5.6-6.8) months in RT alone (P < 0.001), which remained
significant after propensity score matching. CONCLUSIONS: An increase in trend
for the use of immunotherapy was noted, however, an overwhelming majority of the
patients with this disease are still treated without immunotherapy. Addition of
immunotherapy to RT is associated with improved OS in MBM. Given the selection
biases that are inherent in this analysis, prospective trials investigating the
combination of RT, especially SRS and immunotherapy are warranted.
PMID- 29960686
TI - Selenium analysis in waters. Part 1: Regulations and standard methods.
AB - Selenium is released into the aquatic environment through anthropogenic
activities such as agricultural irrigation, coal mining, and metallurgical
activities, where it acts as a reproductive toxin with negative effects on
predatory fish and water fowl. Waterborne selenium concentrations are closely
regulated worldwide, and various standardized methods are implemented by
regulatory bodies to allow for the monitoring of selenium concentrations in
different types of waters. Here, we discuss worldwide regulations relating to
concentration limits of selenium in drinking, natural, and industrial waters.
Focusing specifically on North America, we look at some standardized analysis
methods and discuss the fact that many of these methods are not adequately
sensitive to measure selenium in the concentrations outlined by the associated
regulations for natural waters. We look in detail at the limitations of these
methods with regards to both detection limits and interfering sample matrix
components and establish the need for more sensitive and robust methods of
analysis for regulatory compliance. This review is complemented by a second part
(LeBlanc et al., 2018) where we discuss the state of selenium speciation analysis
and importance of speciation data for decision makers in industry and regulators.
PMID- 29960687
TI - Dynamic Gender Presentations: Understanding Transition and "De-Transition" Among
Transgender Youth.
AB - The following clinical scenarios are composite cases that illustrate clinically
important phenomena based on several patients. Jamie is a 19-year-old who was
assigned a female gender at birth and had a history of major depressive disorder
in remission. She presented to her primary care physician, psychiatrist, and
psychotherapist reporting dysphoria related to gender and requesting gender
affirming hormone therapy. Jamie had symptoms for at least 6 months consistent
with DSM-5 criteria for gender dysphoria. After full clinical assessment by her
therapist, psychiatrist, and primary care physician, her integrated care team
initiated gender-affirming hormone therapy and provided close follow-up from her
mental health providers. For 13 months, Jamie was treated with testosterone,
changed her pronouns to he/him/his, and began wearing traditionally masculine
clothing. Throughout this period, she remained engaged in regular care with her
psychotherapist, who was experienced in providing gender-affirming care.
Eventually, Jamie informed her care team that after the trial of testosterone and
much reflection, she had come to understand her identity as a queer woman and
wished to discontinue hormone therapy. Jamie reported being pleased about the
hormone therapy trial, because this allowed her to clarify her gender identity.
She did not regret her social affirmation or any physical changes that occurred
during this process, such as fat redistribution and minor facial hair growth, in
the context of otherwise being healthy. Lupita is a 23-year-old who was assigned
a male gender at birth and had a history of major depressive disorder and panic
disorder. At 18 years of age, after a comprehensive evaluation, she initiated
gender-affirming hormone therapy with her primary care provider, changed her name
to "Lupita," changed her pronouns to she/her/hers, and started wearing more
traditionally feminine clothing. That following year, she started attending
college and faced continual gender-based harassment from other students as a
result of her gender-nonconforming physical appearance. Her college health
services were not affirming of her gender and referred to her repeatedly by her
birth name and with he-series pronouns. Lupita became demoralized and after 5
months decided to de-transition. She became progressively more depressed and
attempted suicide in her sophomore year. Then she transferred colleges, found
gender-affirming clinical providers, and resumed estradiol and spironolactone (an
antiandrogen) therapy and her social affirmation through name, pronouns, and
style of dress. Her mood improved dramatically and she was able to graduate from
college. Lupita now presents seeking breast augmentation surgery.
PMID- 29960688
TI - Pioneering Research Into Specificity of Intergenerational Transmission of
Interpretation Biases From Parents to Children: Challenges for the Future.
AB - Childhood anxiety disorders are highly prevalent and debilitating psychiatric
conditions. Numerous studies have shown that anxiety disorders run in families.
Children of anxiety-disordered parents have an elevated risk of developing an
anxiety disorder as compared to children of nonanxious parents.1 However, it is
not yet fully understood which mechanisms contribute to the familial aggregation
of anxiety disorders.
PMID- 29960689
TI - Treating a Child With Anxiety and Attention-Deficit/Hyperactivity Disorder? Don't
Rule Out Cognitive-Behavioral Therapy.
AB - Anxiety disorders (ADs) and attention deficit/hyperactivity disorder (ADHD) are
two of the most common psychiatric disorders in youth and approximately 25% of
those with an AD have comorbid ADHD.1 Children with AD and ADHD evidence greater
impairment than those with either disorder alone, making them a particularly
vulnerable population in need of effective treatment.2 Although a strong evidence
base supports the efficacy of cognitive-behavioral therapy (CBT) for treating
anxiety in children,3 there is little information to guide practitioners on how
to best treat those dually diagnosed with an AD and ADHD. Questions have arisen
as to whether the cognitive, attentional, and behavioral impairments associated
with ADHD interfere with the ability of these children to benefit from CBT for
anxiety.4 Does the distractibility and overactivity characteristic of ADHD
inhibit, perhaps differentially, the ability of these children to effectively
engage in CBT for anxiety (e.g., psychoeducation, cognitive restructuring,
therapeutic exposure)?
PMID- 29960690
TI - Identity, Conformity, and Nonconformity: A Closer Look.
AB - As clinicians, we have been vigilant to screen for underlying psychopathology in
children and adolescents who meet criteria for gender dysphoria (GD) based on the
risk these individuals have for developing externalizing and/or internalizing
disorders, likely driven by a stigmatizing society. However, we have not paid
careful attention to an often overlooked population, namely gender-nonconforming
(GNC) children-especially those in community samples-who do not meet criteria for
GD per se but who, according to the well-done and thought-provoking study
featured in this issue, van der Miesen et al.'s "Behavioral and Emotional
Problems in Gender-Nonconforming Children: A Canadian Community-Based Study,"1
appear to share some similar psychiatric vulnerabilities as their peers with GD,
with some unique features noted for natal boys versus natal girls. The few
studies that have looked at this group of children have relied on clinical
samples, which complicates whether the increased rates of psychopathology are in
fact due to GNC-related factors versus inherently higher rates of psychopathology
in clinical samples. Because of this, previous studies using clinical samples
might overestimate the rates of psychopathology in GNC youths. Van der Miesen et
al. smartly attempted to avoid that bias by drawing participants from the
community and by excluding participants with any previous mental health
diagnoses, including GD.1 This study is a refreshing shift, delving into
community samples and using a validated measure, the Gender Identity
Questionnaire for Children (GIQC), thus allowing comparisons to be made with
prior clinical samples.
PMID- 29960691
TI - Biases in Interpretation as a Vulnerability Factor for Children of Parents With
an Anxiety Disorder.
AB - OBJECTIVE: Children of parents with an anxiety disorder have a higher risk of
developing an anxiety disorder than children of parents without an anxiety
disorder. Parental anxiety is not regarded as a causal risk factor itself, but is
likely to be mediated via other mechanisms, for example via cognitive factors. We
investigated whether children of parents with an anxiety disorder would show an
interpretation bias corresponding to the diagnosis of their parent. We also
explored whether children's interpretation biases were explained by parental
anxiety and/or children's levels of anxiety. METHOD: In total, 44 children of
parents with a panic disorder (PD), 27 children of parents with a social anxiety
disorder (SAD), 7 children of parents with SAD/PD, and 84 children of parents
without an anxiety disorder (controls) participated in this study. Parents and
children filled out the Screen for Child Anxiety Related Disorders (SCARED)
questionnaire, and children performed two ambiguous scenario tasks: one with and
one without video priming. RESULTS: Children of parents with PD displayed
significantly more negative interpretations of panic scenarios and social
scenarios than controls. Negative interpretations of panic scenarios were
explained by parental PD diagnosis and children's anxiety levels. These effects
were not found for children of parents with SAD. Priming did not affect
interpretation. CONCLUSION: Our results showed that children of parents with PD
have a higher chance of interpreting ambiguous situations more negatively than
children of parents without anxiety disorders. More research is needed to study
whether this negative bias predicts later development of anxiety disorders in
children.
PMID- 29960692
TI - Results From the Child/Adolescent Anxiety Multimodal Extended Long-Term Study
(CAMELS): Primary Anxiety Outcomes.
AB - OBJECTIVE: To report anxiety outcomes from the multisite Child/Adolescent Anxiety
Multimodal Extended Long-term Study (CAMELS). Rates of stable anxiety remission
(defined rigorously as the absence of all DSM-IV TR anxiety disorders across all
follow-up years) and predictors of anxiety remission across a 4-year period,
beginning 4 to 12 years after randomization to 12 weeks of medication, cognitive
behavioral therapy (CBT), their combination, or pill placebo were examined.
Examined predictors of remission included acute treatment response, treatment
assignment, baseline child and family variables, and interim negative life
events. METHOD: Data were from 319 youths (age range 10.9-25.2 years; mean age
17.12 years) originally diagnosed with separation, social, and/or generalized
anxiety disorders and enrolled in the multi-site Child/Adolescent Anxiety
Multimodal Study (CAMS). Participants were assessed annually by independent
evaluators using the age-appropriate version of the Anxiety Disorders Interview
Schedule and completed questionnaires (eg, about family functioning, life events,
and mental health service use). RESULTS: Almost 22% of youth were in stable
remission, 30% were chronically ill, and 48% were relapsers. Acute treatment
responders were less likely to be in the chronically ill group (odds ratio =
2.73; confidence interval = 1.14-6.54; p < .02); treatment type was not
associated with remission status across the follow-up. Several variables (eg,
male gender) predicted stable remission from anxiety disorders. CONCLUSION:
Findings suggest that acute positive response to anxiety treatment may reduce
risk for chronic anxiety disability; identified predictors can help tailor
treatments to youth at greatest risk for chronic illness. CLINICAL TRIAL
REGISTRATION INFORMATION: Child and Adolescent Anxiety Disorders (CAMS).
http://clinicaltrials.gov/; NCT00052078.
PMID- 29960693
TI - Cognitive-Behavioral Therapy for Children With Anxiety and Comorbid Attention
Deficit/Hyperactivity Disorder.
AB - OBJECTIVE: To determine whether comorbid attention-deficit/hyperactivity disorder
(ADHD) diagnosis (including subtype) predicts response to cognitive-behavior
therapy (CBT) for anxiety in children and to examine change in ADHD symptoms
after treatment of primary anxiety. METHOD: A sample of 842 children 5 to 18
years of age received CBT for a primary anxiety disorder. A subsample of 94
children met criteria for comorbid mild-to-moderate ADHD, mostly consisting of
predominantly inattentive (n = 61) and combined (n = 27) subtypes. Outcome was
defined as response (change in diagnostic severity) and remission (absence of the
primary diagnosis) at each time point (after treatment and 3- and/or 6-month
follow-up) and analyzed using linear and logistic mixed models. RESULTS: Neither
ADHD diagnosis nor subtype predicted response or remission rates for children's
primary anxiety disorders. Children with ADHD also showed modest yet significant
improvements in ADHD symptoms after CBT for anxiety. CONCLUSION: The present
findings support the suitability of manual-based group-based CBT for anxiety
treatment in children with nonprimary ADHD. Further research should examine
whether the positive outcomes reported can be extended to children with primary
or severe ADHD.
PMID- 29960694
TI - Behavioral and Emotional Problems in Gender-Nonconforming Children: A Canadian
Community-Based Study.
AB - OBJECTIVE: To examine childhood gender nonconformity (GNC) and psychological well
being in a community-based sample using measures that bridge clinical and
nonclinical literature. METHOD: Caregivers reported on the GNC (Gender Identity
Questionnaire for Children [GIQC]) and behavioral and emotional problems (Child
Behavior Checklist [CBCL]) of their children aged 6 to 12 years (N = 1719, 48.8%
boys). The GIQC was compared to the commonly used single-item proxy, CBCL Item
110 ("wishes to be of the opposite sex"). RESULTS: Using the GIQC, 2.3% of boys
and 2.8% of girls showed GNC levels comparable to those of children referred
clinically for gender dysphoria (GD). Item 110 was endorsed for 1.7% of boys and
1.8% of girls. These measures corresponded, but Item 110 endorsement was biased
toward more extreme GNC. Among boys, increased GNC on the GIQC, but not Item 110,
corresponded with increased clinical-range CBCL problems. Among girls, Item 110
endorsement was associated with increased clinical-range Externalizing problems,
whereas the GIQC indicated that intermediate gender expression was associated
with fewer externalizing problems. Overall, rates of clinical-range CBCL problems
among GNC children were consistent with those reported for GD-referred children.
CONCLUSION: The scope of mental health risk among community children who exhibit
GNC is likely considerably greater than previously recognized. A substantial
minority of community children show GNC and mental health risk levels comparable
to those seen among GD-referred children. Also, compared to the GIQC, a more
comprehensive GNC measure, CBCL Item 110 is likely useful only for detecting
extreme manifestations of GNC, which may affect associations with mental health.
PMID- 29960695
TI - Strengthening College Students' Mental Health Knowledge, Awareness, and Helping
Behaviors: The Impact of Active Minds, a Peer Mental Health Organization.
AB - OBJECTIVE: To examine the relationship between college students' familiarity with
and involvement in Active Minds, a student peer organization focused on
increasing mental health awareness, decreasing stigma, and affecting mental
health knowledge, attitudes, and behaviors. METHOD: Students (N = 1,129) across
12 California colleges completed three waves of a web-based survey during the
2016-2017 academic year to assess familiarity with and involvement in Active
Minds and mental health attitudes, behaviors, and perceived knowledge. Fixed
effects models assessed relations between changes in organization familiarity and
involvement and changes in mental health-related outcomes over time overall and
stratified by students' baseline engagement (ie, familiarity/involvement) with
Active Minds. RESULTS: Overall, increased familiarity with Active Minds was
associated with increases in perceived knowledge (0.40; p < .001) and decreases
in stigma over time (-0.33; p < .001). Increased involvement was associated with
increases in perceived knowledge (0.40; p < .001) and a range of helping
behaviors. Associations differed by students' baseline engagement with Active
Minds. For students with low engagement, increased familiarity with Active Minds
was associated with decreased stigma and improved perceived knowledge. For
students with moderate baseline engagement, increasing involvement with Active
Minds was associated with increases in helping behaviors (eg, providing emotional
support, connecting others to services) over time. CONCLUSION: Student peer
organizations' activities can improve college student mental health attitudes and
perceived knowledge and significantly increase helping behaviors. Such
organizations can complement more traditional programs and play an important role
in improving the campus climate with respect to mental health.
PMID- 29960696
TI - Postdischarge Suicide and Death in South Korean Children and Adolescents
Hospitalized for a Psychiatric Illness.
AB - OBJECTIVE: The postdischarge suicide rate in children and adolescents ever
hospitalized for a psychiatric illness is much higher than that of children and
adolescents in the general population. We aimed to investigate the postdischarge
death and suicide among children and adolescents hospitalized for a psychiatric
illness using the Korean National Health Insurance database and causes of death
statistics from the National Statistics Office. METHOD: We identified children
and adolescents less than 18 years of age who experienced at least one
psychiatric hospitalization from 2008 to 2013 with a principal diagnosis of a
psychiatric disorder based on the International Classification of Diseases, 10th
Revision, Code Fxx.x). Postdischarge deaths (all-cause death or suicide) after
the first psychiatric hospitalization were investigated. RESULTS: The total
number of patients hospitalized for a psychiatric illness was 14,097, and the
numbers of all-cause deaths and suicide deaths after discharge were 93 and 64,
respectively. The rates of suicide according by diagnostic group were 440.1 (per
100,000 person-years) for psychosis, 248.8 for depression, 155.4 for conduct
disorder, 153.6 for bipolar disorder, 103.4 for posttraumatic stress disorder,
93.0 for anxiety disorder, and 38.4 for attention-deficit/hyperactivity disorder.
CONCLUSION: As suicide is the main cause of postdischarge death, there is an
urgent need to develop and implement effective prevention strategies after
psychiatric hospitalization.
PMID- 29960697
TI - Trends in Children's Mental Health Services Research Funding: Response to
Hoagwood and Colleagues' Commentary.
AB - In their recent JAACAP Commentary, Hoagwood et al.1 examined data extracted from
the National Institutes of Health Research Portfolio Online Reporting Tools
(RePORT) and concluded there has been a decrease in National Institute of Mental
Health (NIMH) funding for child and adolescent services and intervention research
during the 10-year period from 2005 to 2015. They eloquently argued for the
importance of research that can guide practice and inform the organization and
delivery of children's mental health services in the current context of unmet
need and the state of mental health service delivery.
PMID- 29960698
TI - Is the Right Research Being Done to Guide the Development of the American Academy
of Child and Adolescent Psychiatry's Practice Parameters?
AB - The American Academy of Child and Adolescent Psychiatry (AACAP) developed
Practice Parameters (PPs) to provide recommendations regarding the assessment and
treatment of children and adolescents with mental health disorders. Each
recommendation comes with a rating, based on the level of evidence. In descending
order, recommendations are rated as a clinical standard (CS), clinical guideline,
or clinical option (CO), as well as recommendations that are "not endorsed" due
to ineffectiveness or contraindication. According to the PPs, a recommendation is
rated as a CS if it is supported by "rigorous empirical evidence and/or
overwhelming clinical consensus," whereas, the lower quality recommendations,
rated as COs, are founded on "emerging empirical evidence (e.g. uncontrolled
trials or case series/reports) or clinical opinion, but lack strong evidence
and/or strong clinical consensus." Based on the current definition, clinicians
may be perpetuating practices that are based on as little as expert opinion. We
are aware that AACAP is in the process of transitioning from PPs to Clinical
Practice Guidelines (CPGs), which will embody a systematic approach to reconcile
recommendations with national guidelines. In accordance with these higher
standards, we believe that our evaluation of the research gaps will elucidate the
need to encourage resource allocation in deficient areas.
PMID- 29960699
TI - Catatonia in Children and Adolescents: A High Rate of Genetic Conditions.
AB - Pediatric catatonia is a rare and severe neuropsychiatric syndrome. We previously
reported, in 58 children and adolescents with catatonia, a high prevalence (up to
20%) of medical conditions, some of which have specific treatments.1 Here we
extend the cohort inclusion and report the first systematic molecular genetic
data for this syndrome. Among the 89 patients consecutively admitted for
catatonia (according to the pediatric catatonia rating scale)2 between 1993 and
2014, we identify 51 patients (57.3%) who had genetic laboratory testing, of whom
37 had single nucleotide polymorphism (SNP) microarray tests for CNVs and 14 had
routine genetic explorations (karyotyping and searches for specific chromosomal
abnormalities by fluorescence in situ hybridization [FISH]) or a specific
diagnosis test based on clinical history. To assess the causality of observed
genetic findings in each patient, we used a causality assessment score (CAUS)3
including 5 causality-support criteria on a 3-point scale (0 = absent; 1 =
moderate; 2 = high): the existence of similar cases in the literature; the
presence of a clinical contributing factor; the presence of a biological
contributing factor; the presence of other paraclinical symptoms; and response to
a specific treatment related to the suspected genetic or medical condition.
PMID- 29960700
TI - A Peace of Advice.
PMID- 29960701
TI - Autologous stem cell ovarian transplantation to increase reproductive potential
in patients who are poor responders.
AB - OBJECTIVE: To evaluate effects of autologous stem cell ovarian transplant (ASCOT)
on ovarian reserve and IVF outcomes of women who are poor responders with very
poor prognosis. DESIGN: Prospective observational pilot study. SETTING:
University hospital. PATIENT(S): Seventeen women who are poor responders.
INTERVENTION(S): Ovarian infusion of bone marrow-derived stem cells. MAIN OUTCOME
MEASURE(S): Serum antimullerian hormone levels and antral follicular count (AFC),
punctured follicles, and oocytes retrieved after stimulation (controlled ovarian
stimulation) were measred. Apheresis was analyzed for growth factor
concentrations. RESULT(S): The ASCOT resulted in a significant improvement in AFC
2 weeks after treatment. With an increase in AFC of three or more follicles
and/or two consecutive increases in antimullerian hormone levels as success
criteria, ovarian function improved in 81.3% of women. These positive effects
were associated with the presence of fibroblast growth factor-2 and
thrombospondin. During controlled ovarian stimulation, ASCOT increased the number
of stimulable antral follicles and oocytes, but the embryo euploidy rate was low
(16.1%). Five pregnancies were achieved: two after ET, three by natural
conception. CONCLUSION(S): Our results suggest that ASCOT optimized the
mobilization and growth of existing follicles, possibly related to fibroblast
growth factor-2 and thrombospondin-1 within apheresis. The ASCOT improved
follicle and oocyte quantity enabling pregnancy in women who are poor responders
previously limited to oocyte donation. CLINICAL TRIAL REGISTRATION NUMBER:
NCT02240342.
PMID- 29960702
TI - In vivo characterization of metabolic activity and oxidative stress in grafted
human ovarian tissue using microdialysis.
AB - OBJECTIVE: To characterize oxidative stress and metabolic activity in xenografted
human ovarian tissue using microdialysis. DESIGN: Prospective experimental study.
SETTING: Gynecology research unit at a university hospital. PATIENT(S):
Cryopreserved ovarian cortex from five women 27-35 years of age. INTERVENTION(S):
Frozen-thawed human ovarian tissue fragments were xenografted to the back muscle
of ten nude mice. Before grafting, a microdialysis probe was placed inside each
fragment. MAIN OUTCOME MEASURE(S): Daily reactive oxygen species (ROS), lactate,
and glucose levels were collected by means of microdialysis. Follicle loss
(hematoxylin and eosin), murine and human vascularization, and vessel stability
(CD31, von Willebrand factor, and alpha-smooth muscle actin triple
immunofluorescence) were analyzed on post-grafting days 10 and 21. RESULT(S):
Lactate levels were significantly higher than glucose levels until day 10, after
which time the lactate-glucose ratio stabilized at ~1:1. Regarding ROS
generation, there were two peaks on post-grafting days 10 and 17. Total
vascularization increased significantly up to day 10 and remained similar up to
day 21. However, murine vessel area and stabilization significantly increased up
to day 21. Major follicle loss occurred in the first 10 days after
transplantation. CONCLUSION(S): Our data validated microdialysis as a tool to
characterize metabolic behavior and oxidative stress in grafted ovarian tissue.
Three different post-grafting periods were identified according to the metabolic
activity of grafted tissue, showing a long progression from anaerobic to aerobic
metabolism and a protracted period of ROS generation. Oxidative stress was
observed relatively late, after the most critical period of follicle loss, and
lasted until the tissue vasculature stabilized.
PMID- 29960703
TI - Diabetes mellitus and insulin resistance in mothers, fathers, sisters, and
brothers of women with polycystic ovary syndrome: a systematic review and meta
analysis.
AB - OBJECTIVE(S): To analyze whether first-degree relatives (FDR) of patients with
polysystic ovary syndrome (PCOS) have an increased risk of insulin resistance and
glucose intolerance. DESIGN: Systematic review and meta-analysis. SETTING: None.
PATIENT(S): Parents and siblings of women with and without PCOS. INTERVENTION(S):
Search of PubMed database from 1960 to September 2017 with cross-checking of
references of relevant articles in English. MAIN OUTCOME MEASURE(S): Prevalence
of type 2 diabetes mellitus (T2DM) and impaired glucose tolerance, and levels of
fasting insulin, 2-hour insulin levels, and homeostatic model assessment insulin
resistance (HOMA IR). RESULT(S): Our search retrieved 4,796 articles of which 19
were included. The prevalence of T2DM was significantly increased in mothers and
fathers of PCOS probands (rate ratio [RR] 2.43; 95% confidence interval [CI],
1.58-3.75, and RR 2.27; 95% CI, 1.25-4.12). Moreover, the fasting insulin (in
mothers, fathers, and sisters) and HOMA IR (in mothers, fathers, and sisters)
levels were statistically significantly higher in parents and siblings of PCOS
patients. The sisters (RR 1.34; 95% CI, 0.59-3.03) and brothers (RR 1.51; 95% CI,
0.63-3.62) had a higher prevalence of T2DM than the control subjects, but the
difference was not statistically significant. CONCLUSION(S): Our meta-analysis
provides quantitative evidence demonstrating clustering of T2DM and insulin
resistance in the parents and siblings of PCOS probands. SYSTEMATIC REVIEW
REGISTRATION NUMBER: PROSPERO 2016 CRD42016048551.
PMID- 29960704
TI - Endometritis: new time, new concepts.
AB - Endometritis is subdivided into two categories. Acute endometritis is symptomatic
and characterized by microabscess formation and neutrophil invasion in the
endometrial superficial epithelium, gland lumina, and uterine cavity. Chronic
endometritis is rather silent and recognized as unusual plasmacyte infiltration
in the endometrial stromal areas. Over the last decade, studies have disclosed
the potential association between poor reproductive outcomes and endometritis,
particularly chronic endometritis. The aim of this review is to address the
current literature surrounding chronic endometritis and highlight recent advances
in the research of this long-neglected gynecologic disease.
PMID- 29960705
TI - Antimullerian hormone: Don't put all the eggs in one basket.
PMID- 29960706
TI - Development of a question prompt list for women with polycystic ovary syndrome.
AB - OBJECTIVE: To develop a question prompt list (QPL) for women with polycystic
ovary syndrome (PCOS) and explore its acceptability and feasibility. DESIGN:
Nationwide online survey, interviews, and clinical pilot test. SETTING:
Australia. PATIENT(S): Two-hundred and forty-nine women online, 18 women in
interviews, and 20 women in clinics. INTERVENTION(S): A QPL for PCOS. MAIN
OUTCOME MEASURE(S): From survey, women's likeliness to use a QPL and priority
topics; from interview, QPL user-friendliness and associated feelings; from
pilot, women's QPL use, perceived helpfulness, and intended future use.
RESULT(S): Evidence-based guidelines and multidisciplinary experts informed the
QPL development. Of 249 survey respondents, 66.7% to 68.7% reported difficulty
communicating with health care providers about mood, weight management, and how
PCOS affects daily life, and 85.8% indicated they were very likely to use a PCOS
QPL. Women were interviewed to explore acceptability; the semistructured
interviews (n = 18) revealed that the devised QPL was easy to understand, user
friendly, and encouraged information seeking and targeted question asking. The
refined QPL was pilot-tested in a clinic setting to explore feasibility between
2016 and 2017: 60.0% of women asked 1 to 2 questions from the QPL, 20.0% asked
several questions, and 10.0% reported the QPL helped them generate their own
questions. Women agreed the QPL was helpful (95.0%) and that they would use the
QPL again (90.0%). CONCLUSION(S): The PCOS QPL is acceptable and feasible, and
may assist women in information seeking and targeted question asking.
PMID- 29960707
TI - Pushing the limits of detection: investigation of cell-free DNA for aneuploidy
screening in embryos.
AB - OBJECTIVE: To determine the accuracy of cell-free DNA (cfDNA) in spent embryo
medium (SEM) for ploidy and sex detection at the cleavage and blastocyst stages.
To determine if assisted hatching (AH) and morphologic grade influence cfDNA
concentration and accuracy. DESIGN: Prospective cohort. SETTING: Academic
fertility center. PATIENT(S): Nine patients undergoing IVF; 41 donated two
pronuclei embryos and 20 embryos from patients undergoing preimplantation genetic
testing for aneuploidy (PGT-A). INTERVENTIONS(S): In a donated embryo arm, SEM
was collected on days 3 and 5, with one-half of the embryos undergoing AH before
and one-half after. In a clinical arm, SEM was collected on day 5 before
trophectoderm (TE) biopsy. Samples underwent PGT-A with the use of next
generation sequencing. cfDNA results were compared with corresponding whole
embryos and TE biopsies. MAIN OUTCOME MEASURE(S): Concordance rates, sensitivity,
specificity, positive predictive value (PPV), and negative predictive value (NPV)
for ploidy and sex detection with the use of cfDNA. RESULT(S): Of 141 samples,
cfDNA was amplified in 39% and 80.4% of days 3 and 5 SEM, respectively.
Concordances for ploidy and sex, respectively, were 56.3% and 81.3% between day 3
cfDNA and whole embryos, and 65% and 70% between day 5 cfDNA and TE biopsies. Day
5 cfDNA sensitivity and specificity for aneuploidy were 0.8 and 0.61,
respectively. PPV and NPV were 0.47 and 0.88, respectively. Timing of AH and
morphology did not influence cfDNA concentration or accuracy. CONCLUSION(S):
cfDNA is detectable on days 3 and 5, but more accurate on day 5. Although our
data suggest moderate concordance rates, PGT-A with the use of cfDNA must be
further optimized before clinical implementation.
PMID- 29960708
TI - Multicenter evaluation of the Access AMH antimullerian hormone assay for the
prediction of antral follicle count and poor ovarian response to controlled
ovarian stimulation.
AB - OBJECTIVE: To evaluate a new fully automated antimullerian hormone (AMH) assay
for prediction of poor ovarian response (POR) to ovarian stimulation defined as
four or fewer oocytes retrieved. DESIGN: Prospective cohort study. SETTING:
Thirteen private and academic fertility centers in the United States.
PATIENTS(S): A total of 178 women undergoing their first in vitro fertilization
(IVF) cycle eligible for the study were consented and enrolled, with data
available from 160 women for prediction of POR and 164 women for AMH correlation
with antral follicle count (AFC). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff
point for AMH that correlates with antral follicle count >15. RESULT(S): The mean
AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal
to high responders. The AMH cutoff at 90% specificity for predicting POR with the
use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an
associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that
AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH
(AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho =
0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of
59.1%. CONCLUSION(S): A fully automated AMH assay can be a useful biomarker for
predicting POR in IVF cycles. Because AMH cutoff points vary depending on the
assay used, future studies should continue to calibrate test results to
clinically important outcomes.
PMID- 29960709
TI - Non-aspirin NSAID use and ovarian cancer mortality.
AB - OBJECTIVE: Preclinical studies suggest that non-aspirin non-steroidal anti
inflammatory drugs (NSAIDs) may improve survival of ovarian cancer. We examined
the association between non-aspirin NSAID use and ovarian cancer mortality.
METHODS: All women in Denmark with a first diagnosis of epithelial ovarian cancer
between 2000 and 2012 were identified. We obtained information on drug use,
mortality outcomes, and potential confounding factors from nationwide registries.
Cox regression models were used to estimate hazard ratios (HRs) and 95%
confidence intervals (CIs) for the association between postdiagnosis non-aspirin
NSAID use (>=1 prescription) and ovarian cancer-specific or other-cause mortality
compared with non-use (no prescriptions). The influence of competing risks was
evaluated using the sub-distribution hazards model proposed by Fine and Gray.
RESULTS: Among 4117 patients, any postdiagnosis use of non-aspirin NSAIDs was not
associated with either ovarian cancer (HR = 0.97, 95% CI = 0.87-1.08) or other
cause (HR = 0.99, 95% CI = 0.77-1.27) mortality, however, inverse associations
for ovarian cancer mortality were observed with high cumulative (HR = 0.75, 95%
CI = 0.60-0.94) or high-intensity (HR = 0.86, 95% CI = 0.72-1.03) postdiagnosis
use of non-aspirin NSAIDs. The associations differed substantially with
histological subtype of ovarian cancer, with only inverse associations observed
for serous ovarian cancer (HR = 0.87, 95% CI = 0.77-0.99). Among a smaller number
of patients with a non-serous tumor, postdiagnosis non-aspirin NSAID use was
associated with increased ovarian cancer mortality. CONCLUSIONS: Any
postdiagnosis use of non-aspirin NSAIDs did not influence ovarian cancer
mortality overall, however, more intensive use was associated with improved
survival of serous ovarian cancer.
PMID- 29960710
TI - Laparoscopic hand-assisted Miami Pouch after pelvic exenteration in 10 steps.
AB - BACKGROUND: Improvements in surgical technique of pelvic exenteration have mainly
occurred in the reconstructive phase of the procedure. Quality of life seems to
be improved when performing continent rather than non-continent urinary diversion
[1]. Unfortunately, Miami continent urinary pouch is a surgical technique not
frequently used among surgeons. METHODS: This video illustrates the creation of a
laparoscopic hand-assisted Miami Pouch in 10 consecutive steps. We present the
case of a patient with an isolated central pelvic recurrence of cervical cancer
who underwent a laparoscopic anterior pelvic exenteration, which is not included
in the film. The surgery was performed by an experienced oncological surgeon in a
French comprehensive cancer center. RESULTS: We split the surgical technique in
the 10 following steps: CONCLUSIONS: Miami Pouch is a urinary reconstructive
procedure that can improve quality of life after pelvic exenteration. As it has
been previously reported, this film illustrates the feasibility of laparoscopic
hand-assisted Miami Pouch after laparoscopic anterior pelvic exenteration [2,3].
A step-by-step comprehensive standardization of surgical techniques shortens
learning curve of training surgeons [4].
PMID- 29960711
TI - Risk reduction of endometrial and ovarian cancer after bisphosphonates use: A
meta-analysis.
AB - OBJECTIVE: Recent epidemiological studies have investigated the associations
between the use of bisphosphonates and the development of endometrial cancer and
ovarian cancer; these studies have shown controversial results. Hence, this meta
analysis was conducted to evaluate the changes in the risks of developing
endometrial and ovarian cancers after using bisphosphonates based on current
evidence. METHODS: A comprehensive search was performed in the MEDLINE, EMBASE,
and Web of Science databases through January 2017. The summary relative risk (RR)
estimates for the effects of the use of bisphosphonates on the risks of
developing endometrial and ovarian cancers were calculated using a random-effects
model. RESULTS: Seven studies were included with a total of 6471 endometrial
cancer cases (7 studies with 213,920 participants) and 6783 ovarian cancer cases
(4 studies with 105,507 participants). This meta-analysis suggested that any use
of bisphosphonates was associated with a significant 27% reduction in the risk of
endometrial cancer (RR = 0.73, 95% CI: 0.58-0.93, P = 0.012), but the reduction
in the risk of ovarian cancer (RR = 0.81, 95% CI: 0.58-1.14, P = 0.227) was not
significant. The protective effects of the use of bisphosphonates against
endometrial cancer are mainly found in postmenopausal women (RR = 0.53, 95% CI:
0.34-0.93, P = 0.012) or in those who have taken bisphosphonates for longer than
1 year (RR = 0.57, 95% CI: 0.35-0.93, P = 0.024). CONCLUSION: This meta-analysis
suggests that the use of bisphosphonates is associated with a reduction in the
risk of endometrial cancer but not ovarian cancer.
PMID- 29960713
TI - Re: "Paediatric cystolitholapaxy through the Mitrofanoff/Monti channel".
PMID- 29960712
TI - Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for
precursor lesions in cervical cancer.
AB - OBJECTIVES: The methylation profile of genes in precursor lesions in cervical
cancer was characterized to improve screening techniques for high-grade
intraepithelial neoplasia. METHODS: A total of 447 cervical cytology samples
obtained from women who underwent colposcopy were examined. The cases were
distributed as follows: (1) cervices without cervical intraepithelial neoplasia
(CIN; n = 152); (2) cervices with a CIN grade of 1 (CIN 1; n = 147); and (3)
cervices with a CIN grade of 2 or 3 (CIN 2/3; n = 148). The methylation pattern
for a panel of 15 genes was analysed by quantitative methylation-specific PCR
(qMSP) and compared between the groups (<=CIN 1 vs. CIN 2+). RESULTS: In the
validation set, seven genes presented significantly different methylation
profiles according to diagnosis, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001),
HIC1 (p = 0.028), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001),
and TERT (p = 0.001). Six genes showed a significant increase in the frequency of
methylation in the presence of hr-HPV, namely, DAPK1 (p = 0.001), EPB41L3 (p =
0.001), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT
(p = 0.001). The methylation of the hsa-miR-124 gene showed sensitivity and
specificity (86.7% and 61.3%, respectively) similar to that of the HPV test
(91.3% and 50.0%, respectively). The independent factors associated with the
diagnosis of CIN 2+ and the methylation of the hsa-miR-124-2 (OR = 5.1), SOX1 (OR
= 2.8), TERT (OR = 2.2), and LMX1A (OR = 2.0) genes were a positive test for hr
HPV (odds ratio [OR] = 5.5). CONCLUSIONS: Hypermethylation of the hsa-miR-124-2,
SOX1, TERT, and LMX1A genes may be a promising biomarker for precursor lesions in
cervical cancer regardless of the hr-HPV status.
PMID- 29960714
TI - Nurses best practices for the management of thrombotic thrombocytopenic purpura.
AB - A group of Canadian apheresis nurses developed best practice for in the
management of thrombotic thrombocytopenic purpura (TTP). The recommendations
address issues related to infusion protocols, preventing and managing adverse
events, comprehensive patient assessments, treatment procedures, as well as pre-
and post- treatment care. The Canadian group encourages institutes to include
nurses on committees that examine recommendations for TTP management.
PMID- 29960715
TI - The effects of beta blockade and clonidine on persistent injury-associated
anemia.
AB - BACKGROUND: Nonselective beta blockade (BB) and clonidine may abrogate
catecholamine-mediated persistent injury-associated anemia. We hypothesized that
critically ill trauma patients who received BB or clonidine would have favorable
hemoglobin (Hb) trends when adjusting for operative blood loss (OBL), phlebotomy
blood loss (PBL), and red blood cell (RBC) transfusion volumes, and that the
effect would be greatest among the elderly, who have higher catecholamine levels.
METHODS: We performed a 4-y retrospective cohort analysis of 280 consecutive
trauma patients with ICU stay >=48 h and moderate/severe anemia. Patients who
received BB or clonidine for >=25% of their hospital stay were grouped as the
BB/clonidine cohort (n = 84); all other patients served as controls (n = 196).
Admission and discharge Hb were used to calculate DeltaHb. OBL, PBL, and RBC
volume were used to calculate adjusted DeltaHb assuming 300 mL RBC = 1 g/dL Hb.
RESULTS: BB/clonidine and control patients had similar age, injury severity,
comorbid illness, and admission Hb. BB/clonidine patients received fewer RBCs
despite greater OBL, though neither association was statistically significant.
BB/clonidine patients had higher discharge Hb (9.9 versus 9.5, P = 0.029) and
adjusted DeltaHb (+1.0 versus -0.8, P = 0.003). Hb curves separated after
hospital day 10. The difference in adjusted DeltaHb between groups increased with
advanced age (all patients: 1.7, >=50 y: 1.8, >=60 y: 2.4, >=70 y: 3.7).
CONCLUSIONS: Critically ill trauma patients receiving BB or clonidine had
favorable Hb trends when accounting for OBL, PBL, and RBC transfusions. These
findings support the hypothesis that BB and clonidine alleviate persistent injury
associated anemia, with strongest effects among the elderly.
PMID- 29960716
TI - Adolescents' receptivity to E-cigarette harms messages delivered using text
messaging.
AB - INTRODUCTION: E-cigarette use among adolescents has dramatically risen since
2011, yet little research has tested e-cigarette harms messages among
adolescents. We conducted a pretest-posttest pilot study to examine adolescents'
receptivity to e-cigarette health harms messages delivered using text messaging.
METHODS: N = 69 adolescents were enrolled in an 8-day pretest-posttest text
messaging study. Participants completed a pretest survey on day one, were texted
one of three e-cigarette health harms messages per day on days two through seven,
and completed a posttest survey on day eight (88% retention). We assessed message
ratings at posttest and knowledge, thoughts, and beliefs about e-cigarette harms
at pretest and posttest. RESULTS: Adolescents rated the three messages favorably,
with both the chemical and brain messages scoring higher than the nicotine
message on fear arousal and perceived message effectiveness. More than one-third
of adolescents showed the messages to others and talked to others about the
messages. At posttest, knowledge about the harms of e-cigarettes, thinking about
the risks of e-cigarettes, and perceived risks of e-cigarettes were all
significantly higher compared to pretest (p < .05). Participants largely adhered
to the text messaging protocol and found the study highly acceptable.
CONCLUSIONS: This pilot study suggests that adolescents are receptive to e
cigarette health harms messages and that delivering such messages using text
messaging is feasible and acceptable. Future research should systematically
develop and test a broad set of e-cigarette health harms messages and examine
their impact in a randomized controlled trial.
PMID- 29960717
TI - A combined fractional flow reserve and optical coherence tomography approach to
guide coronary artery bypass grafting: A pilot study.
PMID- 29960718
TI - Fatal complications associated with surgical left atrial appendage exclusion.
PMID- 29960719
TI - Use of Group Concept Mapping to Identify Patient Domains of Uncertainty That
Contribute to Emergency Department Use.
AB - INTRODUCTION: Prior research suggests that uncertainty related to symptoms is a
driver of emergency department (ED) use, and that patients often leave the ED
with uncertainty not being addressed. Our objective was to engage patients to
identify domains that contribute to feelings of uncertainty and decisions to use
the ED. METHODS: We used Group Concept Mapping, a quasi-qualitative/quasi
quantitative method, to elicit patients' views on how uncertainty related to
experiencing symptoms contributes to decisions to access the ED. Purposive
sampling was used to recruit participants who either sought treatment at the ED
twice within a 30-day period, or visited both the ED and a primary care provider
at least once within the past year. RESULTS: Thirty-four participants engaged in
two rounds of Group Concept Mapping during which participants participated in
structured brainstorming of ideas, followed by ranking and clustering of ideas
into domains. The first round generated 47 idea statements reflecting uncertainty
about consequences, severity, emergency room services, primary care options,
finances, and psychologic concerns. The second round generated 52 idea statements
reflecting uncertainty about self-management, causation, diagnosis and treatment
plan, trust in the provider and institution, accessibility, and alternative care
options. DISCUSSION: Factors that contribute to uncertainty and decision-making
about ED use are both intrinsic (ie, cause, symptom severity) and extrinsic (ie,
finances, accessibility). These domains can inform approaches to measure the
uncertainty that patients experience, and to design and test interventions for
nurses and other providers to help manage patient uncertainty during acute
illness.
PMID- 29960720
TI - Postmortem glycolysis and glycogenolysis: insights from species comparisons.
AB - After an animal is harvested for meat, the skeletal muscle initiates a complex
series of biochemical reactions in an attempt to maintain energy homeostasis. In
order to maintain energy homeostasis, enzymes within the skeletal muscle
metabolize stored carbohydrate into energy under predominantly anaerobic
conditions in a process known as postmortem energy metabolism. Because these
biochemical reactions have the potential to affect meat quality attributes either
positively or negatively, evaluating their regulation postmortem is fundamental
to understanding meat quality. In this review, the regulation of postmortem
glycolytic enzymes will be evaluated. Special consideration will be given to
species-specific quality defects in pigs, poultry, and fish as a means to further
discuss similarities and differences in postmortem glycolysis and glycogenolysis.
PMID- 29960721
TI - Chemometrics and hyperspectral imaging applied to assessment of chemical,
textural and structural characteristics of meat.
AB - Spectroscopy in the visible near-infrared spectral (Vis-NIRS) range combined with
imaging techniques (hyperspectral imaging, HSI) allows assessment of chemical
composition, texture, and meat structure. The use of HSI in the meat and food
industry has observed a significant growth in the last decade, yet its use for
assessment of meat it is not optimal yet. The application of HSI for assessment
of meat is reviewed with focus on its ability to capture meat unique chemical and
structural characteristics. While HSI is widely used for assessment of chemical
composition, a limited number of evidences on its ability to handle the effect of
different sources of variation on the assessment is found. The use of spatially
resolved spectroscopy has been able to detect structural information related to
animal background, muscle type, rigor process and ageing. Similarly the use of
texture features seem to capture unique characteristics of meat.
PMID- 29960722
TI - Meiofaunal communities in four Adriatic ports: Baseline data for risk assessment
in ballast water management.
AB - Ports receive a variety of contaminants related to a wide range of anthropogenic
activities - including ship ballast water (BW) - that ultimately find their way
to sediments. Benthic meiofauna from four Adriatic ports (Ancona, Trieste, Koper,
and Split) was assessed for the main environmental pollutants, to evaluate the
effects of human activities on meiobenthos and identify the most appropriate
descriptor to assess the ecological quality of marine ecosystems. Sediment
analysis demonstrated that Trieste and Split were the most contaminated ports,
followed by Koper and Ancona. All meiofaunal parameters showed high spatial and
temporal variability, in line with the marked heterogeneity of the four ports.
Sand, total organic carbon, and pollutants seemed to be the variables that best
explained meiofaunal patterns. Community structure and rare taxa were the
meiofaunal descriptors that reflected the environmental status and biological
response most accurately. The present data suggest that meiofauna can be used to
assess the biological impact of BW.
PMID- 29960723
TI - High grade serous intraepithelial carcinoma arising in a benign ovarian serous
cyst - a bridge too far?
PMID- 29960724
TI - Surgical extrusion with an atraumatic extraction system: A clinical study.
AB - STATEMENT OF PROBLEM: Clinical studies evaluating the feasibility of a novel
technique for the surgical extrusion of nonrestorable teeth with subgingival
caries are lacking. PURPOSE: The purpose of this clinical study was to
investigate the success rate and incidence of biological and technical
complications after tooth extrusion with an atraumatic extraction system (AES).
MATERIAL AND METHODS: Participants were recruited from 61 consecutive patients
initially referred to a specialist oral surgery practice. Fifty-one participants
who underwent surgical extrusion with an AES followed by endodontic treatment and
coronal restoration could be re-evaluated clinically and radiographically.
RESULTS: The mean observation period was 3.1 years (range: 0.8 to 6.5 years). The
participants varied in age between 24.8 and 86.3 years. The amount of extrusion
was between 2.5 and 5.0 mm (mean 3.2 mm). At recall, 92.2% (47 of 51) of the
extruded teeth were considered successful. All extruded teeth were asymptomatic,
without clinical signs of inflammation. Percussion appeared normal and did not
differ from that of the adjacent teeth, indicating absence of ankylosis.
Transient resorption with a slightly altered root contour was detected in 5 of
the 51 teeth. Minor reduction of the bone level (less than 10%) was detected in 8
of the 51. In a further 2 teeth, bone loss amounted to 25% and 30%. Periapical
periodontitis at recall was seen in 4 of the 51 teeth, and a preexisting
periapical lesion healed in 10 of 13. Root perforation was identified in 3 of the
51, and a further 3 of 11 were not available for recall. Thus, the technical
complication rate was 9.7% (6 of 62). CONCLUSIONS: The AES may be successfully
used for surgical extrusion to save apparently nonrestorable teeth, irrespective
of patient age.
PMID- 29960725
TI - Cortisol response to stress in schizophrenia: Associations with oxytocin, social
support and social functioning.
AB - Previous studies reported attenuated cortisol reactivity as one explanation for
poor social functioning in schizophrenia. Recent research has demonstrated that
both glucocorticoid and oxytocin systems are central to stress regulation. Here,
we studied the associations between basal oxytocin, stress-induced cortisol
levels, and social functioning and social support in schizophrenia. A mock job
interview was used as an ecologically-valid social stressor in 32 schizophrenia
patients. Blood samples were taken before and after stress induction to assess
basal oxytocin and cortisol levels. In addition social functioning and social
support scales were collected. Patients were divided into cortisol responders and
non-responders according to percentage change following stress induction. Our
findings revealed a possible subgroup of patients who did not exhibit attenuated
cortisol responses. Importantly, cortisol responders had generally better social
functioning, but perceived social support was not different between groups. There
was also no evidence of a relationship between cortisol and oxytocin. This study
highlights the heterogeneity of cortisol responses to stress in a schizophrenia
population, and the importance of the relationship between social functioning and
cortisol reactivity. These findings could be relevant when considering
therapeutic interventions that manipulate endocrinology in order to improve real
world functioning.
PMID- 29960727
TI - Reply to: "Controversial points in the obesity paradox in patients with coronary
artery disease".
PMID- 29960726
TI - Not so little differences: variation in hot weather risk to young children in New
York City.
AB - OBJECTIVES: High ambient temperatures are associated with significant health risk
in the United States. The risk to children has been minimally explored, and often
young children are considered as a single age group despite marked physiologic
and social variation among this population from infancy through preschool. This
study explored the heterogeneity of risk of heat among young children. STUDY
DESIGN: Using a time-stratified, case-crossover design, we evaluated associations
between maximum daily temperature (Tmax) and ED visits (n = 1,002,951) to New
York City (NYC) metropolitan area hospitals for children aged 0-4 years in May
September, 2005-2011. METHODS: Conditional logistic regression analysis estimated
risks for an interquartile range of Tmax for 0-6 lag days. Stratified analyses
explored age strata by year, race/ethnic groups, and diagnostic codes.
Sensitivity analyses controlled for same day ambient ozone, particulate matter
<2.5 microns, and relative humidity and, separately, explored race groups without
ethnicity and different diagnostic code groupings. RESULTS: Children ages 0-4
years had increased risk of emergency department visits with increased Tmax on
lag days 0, 1, and 3. The association was strongest on lag day 0, when an
increase in Tmax of 13 degrees F conferred an excess risk of 2.6% (95%
confidence interval [CI]: 2.2-3.0). Stratifying by age, we observed significant
positive associations for same-day exposures, for 1-4 year olds. Children less
than 1 year of age showed a significant positive association with Tmax only on
lag day 3. The race/ethnicity stratified analysis revealed a similar lag pattern
for all subgroups. The diagnostic group analysis showed percent excess risk for
heat-specific diagnoses (16.6% [95% CI: 3.0-31.9]); general symptoms (10.1% [95%
CI: 8.2-11.9]); infectious (4.9% [95% CI: 3.9-5.9]); and injury (5.1% [95% CI:
3.8-6.4]) diagnoses. CONCLUSION: We found a significant risk of ED visits in
young children with elevated Tmax. Risk patterns vary based on age with infants
showing delayed risk and toddlers and preschoolers with same day risk. In
addition, the finding of increased risk of injury associated with higher
temperatures is novel. Altogether, these findings suggest a need for a tailored
public health response, such as different messages to caregivers of different age
children, to protect children from the effects of heat. Next steps include
examining specific subcategories of diagnoses to develop protective strategies
and better anticipate the needs of population health in future scenarios of
climate change.
PMID- 29960728
TI - Design, synthesis and evaluation of novel bivalent beta-carboline derivatives as
multifunctional agents for the treatment of Alzheimer's disease.
AB - To develop potent multi-target ligands against Alzheimer's disease (AD), a series
of novel bivalent beta-carboline derivatives were designed, synthesized, and
evaluated. In vitro studies revealed these compounds exhibited good
multifunctional activities. In particular, compounds 8f and 8g showed the good
selectivity potency on BuChE inhibition (IC50 = 1.7 and 2.7 MUM, respectively),
Abeta1-42 disaggregation and neuroprotection. Compared with the positive control
resveratrol, 8f and 8g showed better activity in inhibiting Abeta1-42
aggregation, with inhibitory rate 82.7% and 85.7% at 25 MUM, respectively.
Moreover, compounds 8e, 8f and 8g displayed excellent neuroprotective activity by
ameliorating the impairment induced by H2O2, okadaic acid (OA) and Abeta1-42
without cytotoxicity in SH-SY5Y cells. Thus, the present study evidently showed
that compounds 8f and 8g are potent multi-functional agents against AD and might
serve as promising lead candidates for further development.
PMID- 29960729
TI - Design, synthesis, and biological evaluation of novel oxadiazole- and thiazole
based histamine H3R ligands.
AB - Histamine H3 receptor (H3R) is largely expressed in the CNS and modulation of the
H3R function can affect histamine synthesis and liberation, and modulate the
release of many other neurotransmitters. Targeting H3R with antagonists/inverse
agonists may have therapeutic applications in neurodegenerative disorders,
gastrointestinal and inflammatory diseases. This prompted us to design and
synthesize azole-based H3R ligands, i.e. having oxadiazole- or thiazole-based
core structures. While ligands of oxadiazole scaffold were almost inactive,
thiazole-based ligands were very potent and several exhibited binding affinities
in a nanomolar concentration range. Ligands combining 4-cyanophenyl moiety as
arbitrary region, para-xylene or piperidine carbamoyl linkers, and/or pyrrolidine
or piperidine basic heads were found to be the most active within this series of
thiazole-based H3R ligands. The most active ligands were in silico screened for
ADMET properties and drug-likeness. They fulfilled Lipinski's and Veber's rules
and exhibited potential activities for oral administration, blood-brain barrier
penetration, low hepatotoxicity, combined with an overall good toxicity profile.
PMID- 29960730
TI - Synthesis and characterization of some atypical sphingoid bases.
AB - Sphingolipids are ubiquitous and abundant components of all eukaryotic and some
prokaryotic organisms. Sphingolipids show a large structural variety not only
between the different species, but also within an individual cell. This variety
is not limited to alterations in the polar headgroups of e.g. glycosphingolipids,
but also affects the lipophilic anchors comprised of different fatty acids on the
one hand and different sphingoid bases on the other hand. The structural
variations within different sphingoid bases e.g. in pathogens can be used to
identify novel biomarkers and drug targets and the specific change in the profile
of common and uncommon sphingolipids are associated with pathological conditions
like diabetes or cancer. Therefore, the emerging field of sphingolipidomics is
dedicated to collect data on the sphingolipidome of a cell and hence to assign
changes therein to certain states of a cell or to pathological conditions. This
powerful tool however is still limited by the availability of structural
information about the individual lipid species as well as by the availability of
appropriate internal standards for quantification. Herein we describe the
synthesis of a variety of 1-deoxy-sphingoid bases. 1-DeoxySphingolipids have
recently acquired significant attention due to its pathological role in the rare
inherited neuropathy, HSAN1 but also as predictive biomarkers in diabetes type
II. Some of the compounds synthesized and characterized herein, have been used
and will be used to elucidate the correct structure of these disease-related
lipids and their metabolites.
PMID- 29960731
TI - Does U=U for breastfeeding mothers and infants? Breastfeeding by mothers on
effective treatment for HIV infection in high-income settings.
AB - Can the campaign Undetectable=Untransmittable (U=U), established for the sexual
transmission of HIV, be applied to the transmission of HIV through breastfeeding?
European AIDS Clinical Society and, to some extent, American guidelines now state
that mothers with HIV who wish to breastfeed should be supported, with increased
clinical and virological monitoring. This Viewpoint summarises existing evidence
on transmission of HIV through breastfeeding, differences in HIV dynamics and
viral load between breastmilk and plasma, and the effects of antiretroviral
therapy on infants. At present, insufficient evidence exists to make clear
recommendations for the required frequency of clinical and virological monitoring
for mother and infant in a breastfeeding relationship or for the action to be
taken in the event of viral rebound. We propose a roadmap for collaborative
research to provide the missing evidence required to enable mothers who wish to
breastfeed to make a fully informed choice.
PMID- 29960733
TI - Plantarflexor moment arms estimated from tendon excursion in vivo are not
strongly correlated with geometric measurements.
AB - Geometric and tendon excursion methods have both been used extensively for
estimating plantarflexor muscle moment arm in vivo. Geometric measures often
utilize magnetic resonance imaging, which can be costly and impractical for many
investigations. Estimating moment arm from tendon excursion measured with
ultrasonography may provide a cost-effective alternative to geometric measures of
moment arm, but how well such measures represent geometry-based moment arms
remains in question. The purpose of this study was to determine whether moment
arms from tendon excursion can serve as a surrogate for moment arms measured
geometrically. Magnetic resonance and ultrasound imaging were performed on 19
young male subjects to quantify plantarflexor moment arm based on geometric and
tendon excursion paradigms, respectively. These measurements were weakly
correlated that approached statistical significance (R2 = 0.21, p = 0.052), and
moment arm from tendon excursion under-approximated geometric moment arm by
nearly 40% (p < 0.001). This weak correlation between methods is at odds with a
prior report (N = 9) of a strong correlation (R2 = 0.94) in a similar study.
Therefore, we performed 92,378 regression analyses (19 choose 9) to determine if
such a strong correlation existed in our study population. We found that certain
sub-populations of the current study generated similarly strong coefficients of
determination (R2 = 0.92), but 84% of all analyses revealed no correlation (p >
0.05). Our results suggest that the moment arms from musculoskeletal geometry
cannot be otherwise obtained by simply scaling moment arms estimated from tendon
excursion.
PMID- 29960732
TI - Modification of a three-compartment muscle fatigue model to predict peak torque
decline during intermittent tasks.
AB - This study aimed to test whether adding a rest recovery parameter, r, to the
analytical three-compartment controller (3CC) fatigue model (Xia and Frey Law,
2008) will improve fatigue estimates during intermittent contractions. The 3CC
muscle fatigue model uses differential equations to predict the flow of muscle
between three muscle states: Resting (MR), Active (MA), and Fatigued (MF). This
model uses a feedback controller to match the active state to target loads and
two joint-specific parameters: F, fatigue rate controlling flow from active to
fatigued compartments) and R, the recovery rate controlling flow from the
fatigued to the resting compartments. This model does well to predict intensity
endurance time curves for sustained isometric tasks. However, previous studies
find when rest intervals are present that the model over predicts fatigue.
Intermittent rest periods would allow for the occurrence of subsequent reactive
vasodilation and post-contraction hyperemia. We hypothesize a modified 3CC-r
fatigue model will improve predictions of force decay during intermittent
contractions with the addition of a rest recovery parameter, r, to augment
recovery during rest intervals, representing muscle re-perfusion. A meta-analysis
compiling intermittent fatigue data from 63 publications reporting decline in
peak torque (% torque decline) were used for comparison. The original model over
predicted fatigue development from 19 to 29% torque decline; the addition of a
rest multiplier significantly improved fatigue estimates to 6-10% torque decline.
We conclude the addition of a rest multiplier to the three-compartment controller
fatigue model provides a physiologically consistent modification for tasks
involving rest intervals, resulting in improved estimates of muscle fatigue.
PMID- 29960734
TI - 3D patient-specific numerical modeling of the soft palate considering adhesion
from the tongue.
AB - Collapse of the soft palate in the upper airway contributes to obstructive
sleeping apnea (OSA). In this study, we investigate the influence of the adhesion
from the tongue on the soft palate global response. This is achieved using a
cohesive zone finite element approach. A traction-separation law is determined to
describe the adhesion effect from the surface tension of the lining liquid
between the soft palate and the tongue. According to pull-off experimental tests
of human lining liquid from the oral surface of the soft palate, the
corresponding cohesive properties, including the critical normal traction stress
and the failure separation displacement, are obtained. The 3D patient-specific
soft palate geometry is accounted for, based on one specific patient's computed
tomography (CT) images. The calculation results show that influence of the
adhesion from the tongue surface on the global response of the soft palate
depends on the length ratio between the cohesive length and the soft palate
length. When the length of the cohesive zone is smaller than half of the soft
palate length, the adhesion's influence is negligible. When the adhesion length
is larger than 70 percent of soft palate length, the adhesion force contributes
to preventing the soft palate from collapsing towards to the pharynx wall, i.e.
the closing pressure is more negative than in the no adhesion case. These results
may provide useful information to the clinical treatment of OSA patients.
PMID- 29960735
TI - Separation and identification of polymeric dispersants in detergents by two
dimensional liquid chromatography.
AB - Polymeric dispersants are an important ingredient in many consumer products.
Their separations and identifications in final product formulation can be very
challenging due to the presence of multiple polymeric dispersants at different
levels and the presence of other polymeric and small-molecule components. In this
study, using nearly comprehensive two-dimensional liquid chromatography (2D-LC),
various water-soluble polymer and co-polymer dispersants were separated with
aqueous size exclusion chromatography (SEC) in the first dimension (1D) and
gradient elution reversed-phase liquid chromatography (RPLC) in the second
dimension (2D). Detection of the polymeric dispersants was accomplished by
evaporative light scattering detector (ELSD). A large ID (8.0 mm) SEC column used
in common one-dimensional SEC practices was directly adopted in the 2D setup for
rapid method development. A close representation of fully comprehensive 2D
separation was achieved even with 60% of 1D eluent diverted to waste,
demonstrating the flexibility and versatility of having SEC in 1D for two
dimensional separation of polymers. Important method parameters, such as 2D
column dimensions and flow rate, gradient conditions, and buffer pH were studied.
Practical aspects of routine industrial applications such as solvent consumption
and analysis time were also considered. This method was exploited for quick
identification of polymeric dispersants in commercial detergent samples. Nine
detergent samples were screened and polymeric dispersants and additional polymer
features were detected in the samples.
PMID- 29960736
TI - Modelling the enantioresolution capability of cellulose tris(3,5
dichlorophenylcarbamate) stationary phase in reversed phase conditions for
neutral and basic chiral compounds.
AB - To the best of our knowledge, the prediction of the enantioresolution ability of
polysaccharides-based stationary phases in liquid chromatography for structurally
unrelated compounds has not been previously reported. In this study, structural
information of neutral and basic compounds is used to model their
enantioresolution levels obtained from an immobilised cellulose tris(3,5
dichlorophenylcarbamate) stationary phase in reversed phase conditions. Thirty
four structurally unrelated chiral drugs and pesticides, from seven families, are
studied. Categorical enantioresolution levels (RsC, 0 = no baseline
enantioresolution and 1 = baseline enantioresolution) are established from the
experimental enantioresolution values obtained at a fixed experimental
conditions. From 58 initial structural variables, three topological parameters
(two of them connected to the chiral carbon), and six molecular descriptors (one
of them also related with the chiral carbon), are selected after a discriminant
partial least squares refinement process. The molar total charge of the molecule
at the working pH is the most important variable. The relationships between RsC
and the most important structural variables and the drug/pesticide family are
evaluated. An explicit model is proposed to anticipate the RsC levels, which
provides 100% of correct anticipations. A criterion is introduced to alert about
the compounds that should not be anticipated.
PMID- 29960737
TI - Matrix solid-phase dispersion associated to gas chromatography for the assessment
in honey bee of a group of pesticides of concern in the apicultural field.
AB - A method based on matrix solid-phase dispersion (MSPD) associated to gas
chromatography-flame photometric detection (GC-FPD), GC-electron capture
detection (GC-ECD) and GC-mass spectrometry (GC-MS) for confirmation purposes,
was developed for the determination of a representative group of twelve
pesticides in honeybee with particular concern in the apicultural field
(fipronil, thiamethoxam, acetamiprid, acrinathrin, metamidophos, dimetoathe,
diazinon, chlorpyrifos, methidathion, profenophos, azinphos methyl and
coumaphos). Factors influencing the extraction efficiency of MSPD were
investigated and optimized through response surface method. The use of
octadecylsilyl (C18) sorbent combined with a florisil clean-up and acetonitrile
methanol (99:1) elution was the optimal condition for the extraction of the
selected pesticides. Under this condition the recovery of pesticides at the limit
of quantification of the method (0.007 to 0.050 MUg g-1) ranged from 68 to 102%
with RSDs for within-laboratory reproducibility <=20%. The proposed method was
applied to the analysis of honeybees collected in 68 field hives from areas of
great apicultural and agricultural development in central Chile. In 65% of these
samples eight different pesticides were detected. Pesticides most frequently
found were chlorpyrifos (34% of the samples, <0.017-0.067 MUg g-1), acrinathrin
(32% of the samples, <0.020-0.026 MUg g-1) and diazinon (10% of the samples at
values <0.015 MUg g-1). The incidence of these pesticides in bees can be related
to their high employ in central Chile, use to combat the varroosis in hives and
hydrophobicity.
PMID- 29960738
TI - Cationic amine-bridged periodic mesoporous organosilica materials for off-line
solid-phase extraction of phenoxy acid herbicides from water samples prior to
their simultaneous enantiomeric determination by capillary electrophoresis.
AB - Two novel materials based on periodic mesoporous organosilica (PMO) with cationic
amine-bridged ligands, (styrylmethyl)bis(triethoxysilylpropyl)ammonium chloride
(PMO-STPA) and bis(3-triethoxysilylpropyl)amine (PMO-TEPA), were synthesized in
this work to obtain materials with reverse-phase/strong anionic exchange mixed
mode or strong anionic exchange retention mechanism, respectively. The resulting
materials were comprehensively characterized and showed functionalization with
cationic amine-bridged ligands, and values of surface areas characteristic of
mesoporous materials (higher than 100m2/g). These materials were evaluated for
the off-line solid-phase extraction (SPE) of a mixture of six phenoxy acid
herbicides (fenoprop, mecoprop, dichlorprop, 2-(4-chlorophenoxy)propionic acid (4
CPPA), 2-(3-chlorophenoxy)propionic acid (3-CPPA), 2-phenoxypropionic acid (2
PPA)) from water samples previous to their analysis by CE with diode-array
detection using a dual chiral selector system (20mM of heptakis(2,3,6-tri-O
methyl)-beta-CD (TM-beta-CD) and 7mM of (2-hydroxypropyl)-beta-CD (HP-beta-CD)
dissolved in 50mM phosphate buffer, pH 7.0) which enabled the simultaneous
enantiomeric separation of the six phenoxy acid herbicides in 11min. SPE
parameters were optimized and recoveries obtained for PMO-STPA and PMO-TEPA
sorbents were compared. Under the optimized conditions, it was demonstrated that
using 100mg of PMO-STPA sorbent, a maximum preconcentration factor (PF) of 1500
was achieved with 750mL of standard solution, allowing recoveries between 75.5
and 112.2%, with good repeatability (RSD=1.9-8.7%, n=6). Analytical
characteristics of the method were evaluated in terms of precision, linearity and
accuracy with method quantitation limits (MQL) between 0.4 and 14.3MUg/L. The
developed method was applied to the analysis of river samples and effluents from
wastewater treatment plants, with recoveries ranging from 78.3 to 107.5%.
PMID- 29960739
TI - Nanoparticle-templated hierarchically porous polymer/zeolitic imidazolate
framework as a solid-phase microextraction coatings.
AB - A two-step ZnO nanoparticle-directed method has been implemented to prepare
polymer monolith/zeolitic imidazolate framework (ZIF) solid-phase microextraction
(SPME) fiber coatings with hierarchical micro-meso-macroporosity. The polymer/ZIF
monolith was prepared on the surface of a stainless steel wire from a
polymerization mixture containing dispersed ZnO nanoparticles. The embedded ZnO
nanoparticles in the precursor polymer monolith coating were converted on-fiber
to submicrometric porous crystals of the prototypical ZIF-8, based on the
coordination of Zn(II) with 2-methylimidazole. The polymer/ZIF monolith coating
was applied to the headspace SPME of benzene, toluene, ethylbenzene, and xylenes
(BTEX) from water samples, followed by gas chromatography-flame ionization
detection (GC-FID). Hierarchically porous polymer/ZIF monolithic coatings showed
a superior performance for BTEX extraction in comparison to coatings based on
pure macroporous organic polymer monoliths, silicone glue/ZIF-8 coatings or
commercial PDMS coatings. Experimental parameters such as desorption temperature,
desorption time, salt concentration, temperature effect, equilibrium time and
extraction time were investigated. Under the selected experimental conditions,
limits of detection of 0.02-0.11 MUg L-1, linear ranges of 0.2-200 MUg L-1,
relative standard deviations of 4.3-8.2%, and a fiber-to-fiber reproducibility of
8.9-9.8% (n = 3) were obtained. Recoveries higher than 88% were obtained for BTEX
analysis in tap water, wastewater and landfill leachates.
PMID- 29960741
TI - Pelvic floor electrical stimulation and muscles training: a combined
rehabilitative approach for management of non-neuropathic urinary incontinence in
children.
AB - PURPOSE: To assess the efficacy of combined transcutaneous interferential (IF)
electrical stimulation and pelvic floor muscle training through biofeedback on
non-neuropathic urinary incontinence in children. METHODS: This prospective study
comprised of 46 anatomically and neurologically normal children (9 boys, 37
girls; mean age of 8.4 +/- 2.2 years old) with non-neuropathic urinary
incontinence. All children were evaluated by kidney and bladder ultrasounds,
uroflowmetry with electromyography (EMG), a complete voiding diary and a
dysfunctional voiding scoring questionnaire at the baseline. Children were
randomly allocated into two treatment groups including group A (n = 23) who
underwent biofeedback therapy in addition to IF electrical stimulation and group
B (n = 23) who received only biofeedback therapy. Re-evaluation was performed 6
months and one year after completion of the treatment sessions. RESULTS:
Improvement of non-neuropathic urinary incontinence was significantly higher in
group A in comparison to group B at two follow ups (P < 0.05). Daytime
incontinence was improved in 19/23(82%) and 13/23(56.5%) of children in groups A
and B respectively after the treatment (P < 0.01). There was no significant
difference in uroflowmetry measures between two groups after the treatment.
CONCLUSIONS: Combination of biofeedback therapy and transcutaneous IF electrical
stimulation is a potential effective modality in treating non-neuropathic urinary
incontinence in children. LEVEL OF EVIDENCE: Type of study: Treatment study.
Level I: Randomized controlled trials with adequate statistical power to detect
differences (narrow confidence intervals) and follow up >80%.
PMID- 29960740
TI - The artificial placenta: Continued lung development during extracorporeal support
in a preterm lamb model.
AB - PURPOSE: An artificial placenta (AP) utilizing extracorporeal life support (ECLS)
could avoid the harm of mechanical ventilation (MV) while allowing the lungs to
develop. METHODS: AP lambs (n = 5) were delivered at 118 days gestational age
(GA; term = 145 days) and placed on venovenous ECLS (VV-ECLS) with jugular
drainage and umbilical vein reinfusion. Lungs remained fluid-filled. After 10
days, lambs were ventilated. MV control lambs were delivered at 118 ("early MV";
n = 5) or 128 days ("late MV"; n = 5), and ventilated. Compliance and oxygenation
index (OI) were calculated. After sacrifice, lungs were procured and H&E-stained
slides scored for lung injury. Slides were also immunostained for PDGFR-alpha and
alpha-actin; alveolar development was quantified by the area fraction of alveolar
septal tips staining double-positive for both markers. RESULTS: Compliance of AP
lambs was 2.79 +/- 0.81 Cdyn compared to 0.83 +/- 0.19 and 3.04 +/- 0.99 for
early and late MV, respectively. OI in AP lambs was lower than early MV lambs
(6.20 +/- 2.10 vs. 36.8 +/- 16.8) and lung injury lower as well (1.8 +/- 1.6 vs.
6.0 +/- 1.2). Double-positive area fractions were higher in AP lambs (0.012 +/-
0.003) than early (0.003 +/- 0.0005) and late (0.004 +/- 0.002) MV controls.
CONCLUSIONS: Lung development continues and lungs are protected from injury
during AP support relative to mechanical ventilation. LEVEL OF EVIDENCE: n/a
(basic/translational science).
PMID- 29960743
TI - The impact of dose reduction on the quantification of coronary artery
calcifications and risk categorization: A systematic review.
AB - Multiple dose reduction techniques have been introduced for coronary artery
calcium (CAC) computed tomography (CT), but few have emerged into clinical
practice while an increasing number of patients undergo CAC scanning. We sought
to determine to what extend the radiation dose in CAC CT can be safely reduced
without a significant impact on cardiovascular disease (CVD) risk stratification.
A systematic database-review of articles published from 2002 until February 2018
was performed in Pubmed, WebOfScience, and Embase. Eligible studies reported
radiation dose reduction for CAC CT, calcium scores and/or risk stratification
for phantom or patient studies. Twenty-eight studies were included, under which
17 patient studies, 10 phantom/ex-vivo studies, and 1 study evaluated both
phantom and patients. Dose was reduced with tube voltage reduction and tube
current reduction with and without iterative reconstruction (IR), and tin-filter
spectral shaping. The different dose reduction techniques resulted in varying
final radiation doses and had varying impact on CAC scores and CVD risk
stratification. In 78% of the studies the radiation dose was reduced by >= 50%
ranging from (CTDIvol) 0.6-5.5 mGy, leading to reclassification rates ranging
between 3% and 21%, depending on the acquisition technique. Specific dose reduced
protocols, including either tube current reduction and IR or spectral shaping
with tin filtration, that showed low reclassification rates may potentially be
used in CAC scanning and in future population-based screening for CVD risk
stratification.
PMID- 29960744
TI - Clinical feasibility and efficiency of a 3-dimensional printed surgical template
for mandibular angle osteotomy and mandibular angle splitting osteotomy.
AB - Mandibular angle osteotomy (MAO) and mandibular angle splitting osteotomy (MASO)
are the two main surgical approaches used to correct a square mandible for a
desirable aesthetic appearance. However, there are concerns about the safety and
accuracy of both procedures as they may lead to unsatisfactory results such as
injury to the nerve. To achieve symmetry and security we designed and evaluated a
3-dimensional printed surgical template, which indicates the outer cortex
splitting line of the MASO, and the curved cutting line of the MAO. We operated
on 11 patients who had been diagnosed with broad mandibles using the assisted
template. The mean duration of osteotomy, degree of numbness of the inferior
alveolar nerve, and reduction in the width of the mandible (Go-Go) were recorded.
The mandibular curve before and after operation was fitted to evaluate its
accuracy. The results showed that mean duration of osteotomy and numbness of the
nerve were reduced, and there was no significant difference between simulation
and postoperatively. The mean (SD) reduction in the mandibular width was 15.2
(1.6)mm. The template facilitated accuracy and safety in both procedures.
PMID- 29960745
TI - Infantile spasms in a mosaic monocentric and duplicated SMC 15 patient.
AB - OBJECTIVE: To report detail of a patient with infantile spasms whose cytogenetic
analysis revealed mosaic monocentric and duplicated supernumerary marker
chromosome (SMC) 15. SUBJECT AND METHODS: The subject for this case was a 13
month-old girl with infantile spasms and delayed developmental milestones.
Chromosomal analysis with G-band showed the presence of SMC in mosaic. Further
investigations using in situ hybridization, methylation-specific multiplex
ligation-dependent probe amplification (MS-MLPA), microsatellite marker, and
single nucleotide polymorphism (SNP) array analysis were performed. RESULTS: Her
karyotype was noted as mosaic 47,XX,+mar[26]/46,XX[4], ish der(15)(D15Z1+,
SNRPN++, PML-) de novo. MS-MLPA analysis showed that the Prader-Willi
syndrome/Angelman syndrome critical region is highly methylated, and
microsatellite marker analysis proved that the 15q11.2 region of the patient
comprises three kinds of alleles: one paternal and two maternal. SNP array
analysis suggested an asymmetric structure of SMC(15) composed of 15q11-q13
recombination at breakpoint (BP) 4:BP5. CONCLUSIONS: This is the first report of
SMC(15) with monocentric and duplicated proximal 15q. The clinical presentations
are quite similar to those of isodicentric chromosome 15 syndrome. The results of
microsatellite and SNP array analysis suggest two possibilities regarding the
timing of the mosaic SMC(15) formation. One possibility is that it occurred
during maternal meiosis, and the other possibility is formation during a very
early stage of embryo development that was initially trisomic of chromosome 15.
PMID- 29960746
TI - The AGES-Reykjavik Study suggests that change in kidney measures is associated
with subclinical brain pathology in older community-dwelling persons.
AB - Decreased glomerular filtration rate (GFR) and albuminuria may be accompanied by
brain pathology. Here we investigated whether changes in these kidney measures
are linked to development of new MRI-detected infarcts and microbleeds, and
progression of white matter hyperintensity volume. The study included 2671
participants from the population-based AGES-Reykjavik Study (mean age 75, 58.7%
women). GFR was estimated from serum creatinine, and albuminuria was assessed by
urinary albumin-to-creatinine ratio. Brain MRI was acquired at baseline (2002
2006) and 5 years later (2007-2011). New MRI-detected infarcts and microbleeds
were counted on the follow-up scans. White matter hyperintensity progression was
estimated as percent change in white matter hyperintensity volumes between the
two exams. Participants with a large eGFR decline (over 3 ml/min/1.73m2 per year)
had more incident subcortical infarcts (odds ratio 1.53; 95% confidence interval
1.05, 2.22), and more marked progression of white matter hyperintensity volume
(difference: 8%; 95% confidence interval: 4%, 12%), compared to participants
without a large decline. Participants with incident albuminuria (over 30 mg/g)
had 21% more white matter hyperintensity volume progression (95% confidence
interval: 14%, 29%) and 1.86 higher odds of developing new deep microbleeds (95%
confidence interval 1.16, 2.98), compared to participants without incident
albuminuria. The findings were independent of cardiovascular risk factors.
Changes in kidney measures were not associated with occurrence of cortical
infarcts. Thus, larger changes in eGFR and albuminuria are associated with
increased risk for developing manifestations of cerebral small vessel disease.
Individuals with larger changes in these kidney measures should be considered as
a high risk population for accelerated brain pathology.
PMID- 29960747
TI - The Aftermath of Zika: Need for Long-Term Monitoring of Exposed Children.
AB - Pregnancy infections with Zika virus are associated with a spectrum of fetal
brain injuries beyond microcephaly. Nonmicrocephalic children exposed to Zika
virus in utero or early life should undergo neurodevelopmental testing to
identify deficits and allow for early intervention. Additionally, long-term
monitoring for higher order neurocognitive deficits should be implemented.
PMID- 29960748
TI - Causes of mortality in older patients with stage 3 colon cancer.
AB - OBJECTIVES: Life expectancy plays a key role in the selection of patients with
stage III colon cancer for adjuvant chemotherapy, but little is known about
causes of mortality in older patients with colon cancer. We aimed to examine
causes of death in this population and compare these causes between patients who
received chemotherapy and those who did not. Specifically, we chose to examine
the rates of death related to recurrent colon cancer versus non colon cancer.
MATERIALS AND METHODS: Patients aged 50 and older diagnosed with stage III colon
cancer between 2005 and 2009 were included. Patients were divided into "younger"
(aged 50-69) and "older" (aged 70+). Causes of death, which were categorized into
colon cancer versus non-colon cancer related. RESULTS: 1361 patients were
included, 50% of whom were 70 or older. Younger patients were more likely to
receive adjuvant chemotherapy (90% vs. 60%). 601 patients died in the follow up
period. Deceased patients in the younger group were more likely to die from colon
cancer (81% vs. 62%). The most common cause of non-colon cancer death was other
primary malignancies in younger patients and cardiovascular diseases in older
patients. In older patients who received chemotherapy, 41% died; 89% of these
deaths were related to colon cancer. In older patients who did not receive
chemotherapy 72% died, with 38% of patients ultimately dying from colon cancer.
CONCLUSIONS: Older patients remain under-treated with chemotherapy. Although non
colon cancer deaths were more frequent in older patients with cancer, colon
cancer was a still a significant cause of mortality. These deaths may be
preventable with adjuvant chemotherapy.
PMID- 29960749
TI - Vesical Imaging-Reporting and Data System (VI-RADS): Added Value for Management
of Bladder Cancer Patients?
PMID- 29960751
TI - A case of alleged discharge of a firearm within a vehicle.
AB - A road-rage altercation occurred between two vehicle drivers. The driver of
vehicle 1 stopped and allegedly fired two shots from within his vehicle over the
heads of the driver and passenger of vehicle 2 when they were out of their
vehicle. The driver of vehicle 2, an off-duty police officer, fired his .45
calibre pistol at the driver of vehicle 1. The bullet went through the windshield
and lodged in the instrument panel. Eight gunshot residue (GSR) samples were
taken from the interior of vehicle 1 and analysed by automated scanning electron
microscopy/energy dispersive x-ray spectroscopy. The results show for vehicle 1
that a firearm discharged with its breach or cylinder gap within the vehicle was
unlikely to have occurred and the .45 calibre bullet which impacted five surfaces
of vehicle 1 was accompanied by GSR throughout its travel. A recreational shooter
is shown in this study to transfer GSR to the seat of his car. The driver of
vehicle 1 visited a recreational gun range prior to the altercation, which would
explain the significant GSR contamination of the driver's seat of his vehicle.
PMID- 29960750
TI - A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating
Clinically Significant Nonmetastatic Prostate Cancer.
AB - BACKGROUND: Clinically significant nonmetastatic prostate cancer (PCa) is
currently treated using whole-gland therapy. This approach is effective but can
have urinary, sexual, and rectal side effects. OBJECTIVE: To report on 5-yr PCa
control following focal high-intensity focused ultrasound (HIFU) therapy to treat
individual areas of cancer within the prostate. DESIGN, SETTING, AND
PARTICIPANTS: This was a prospective study of 625 consecutive patients with
nonmetastatic clinically significant PCa undergoing focal HIFU therapy
(Sonablate) in secondary care centres between January 1, 2006 and December 31,
2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or
high-risk PCa was found in 505 patients (84%). INTERVENTION: Disease was
localised using multiparametric magnetic resonance imaging (mpMRI) combined with
targeted and systematic biopsies, or transperineal mapping biopsies. Areas of
significant disease were treated. Follow-up included prostate-specific antigen
(PSA) measurement, mpMRI, and biopsies. OUTCOME MEASUREMENTS AND STATISTICAL
ANALYSIS: The primary endpoint, failure-free survival (FFS), was defined as
freedom from radical or systemic therapy, metastases, and cancer-specific
mortality. RESULTS AND LIMITATIONS: The median follow-up was 56 mo (interquartile
range [IQR] 35-70). The median age was 65 yr (IQR 61-71) and median preoperative
PSA was 7.2 ng/ml (IQR 5.2-10.0). FFS was 99% (95% confidence interval [CI] 98
100%) at 1 yr, 92% (95% CI 90-95%) at 3 yr, and 88% (95% 85-91%) at 5 yr. For the
whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5
yr was 98% (95% CI 97-99%), 100%, and 99% (95% CI 97-100%), respectively. Among
patients who returned validated questionnaires, 241/247 (98%) achieved complete
pad-free urinary continence and none required more than 1 pad/d. Limitations
include the lack of long-term follow-up. CONCLUSIONS: Focal therapy for select
patients with clinically significant nonmetastatic prostate cancer is effective
in the medium term and has a low probability of side effects. PATIENT SUMMARY: In
this multicentre study of 625 patients undergoing focal therapy using high
intensity focused ultrasound (HIFU), failure-free survival, metastasis-free
survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and
99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy
for patients with clinically significant prostate cancer that has not spread has
a low probability of side effects and is effective at 5 yr.
PMID- 29960752
TI - Respiratory variability of peak velocities in the common femoral vein estimated
with vector flow imaging and Doppler ultrasound.
AB - Respiratory variability of peak velocities (RVPV) in the common femoral vein
measured with ultrasound can reveal venous outflow obstruction. Pulse wave (PW)
Doppler is the gold standard for venous velocity estimation of the lower
extremities. PW Doppler measurements are angle dependent, whereas vector flow
imaging (VFI) can yield angle-independent measures. The hypothesis of the present
study was that VFI can provide RVPV estimations without the angle dependency of
PW Doppler for an improved venous disease assessment. Sixty-seven patients with
symptomatic chronic venous disease were included in the study. On average, VFI
measured a lower RVPV than PW Doppler (VFI: 14.11 cm/s; PW: 17.32 cm/s, p =
0.002) with a non-significant improved precision compared with PW Doppler (VFI:
21.09%; PW: 26.49%, p = 0.08). In a flow phantom, VFI had improved accuracy (p <
0.01) and equal precision compared with PW Doppler. The study indicated that VFI
can characterize the hemodynamic fluctuations in the common femoral vein.
PMID- 29960753
TI - MitraClip Implantation to Treat Early Recurrence of Mitral Regurgitation After
Percutaneous Direct Annuloplasty With Cardioband.
PMID- 29960754
TI - Optical Coherence Tomographic Features of Unstable Coronary Lesions Corresponding
to Histopathological Intraplaque Hemorrhage Evaluated by Directional Coronary
Atherectomy Specimens.
PMID- 29960756
TI - Transcatheter Aortic Valve Replacement in Extremely Large Annuli: (Over)expanding
Bioprosthetic Technology to the Limits?
PMID- 29960755
TI - Impact of Aortic Root Anatomy and Geometry on Paravalvular Leak in Transcatheter
Aortic Valve Replacement With Extremely Large Annuli Using the Edwards SAPIEN 3
Valve.
AB - OBJECTIVES: The aim of this study was to determine factors affecting paravalvular
leak (PVL) in transcatheter aortic valve replacement (TAVR) with the Edwards
SAPIEN 3 (S3) valve in extremely large annuli. BACKGROUND: The largest
recommended annular area for the 29-mm S3 is 683 mm2. However, experience with S3
TAVR in annuli >683 mm2 has not been widely reported. METHODS: From December 2013
to July 2017, 74 patients across 16 centers with mean area 721 +/- 38 mm2 (range:
684 to 852 mm2) underwent S3 TAVR. The transfemoral approach was used in 95%, and
39% were under conscious sedation. Patient, anatomic, and procedural
characteristics were retrospectively analyzed. Valve Academic Research Consortium
2 outcomes were reported. RESULTS: Procedural success was 100%, with 2 deaths, 1
stroke, and 2 major vascular complications at 30 days. Post-dilatation occurred
in 32%, with final balloon overfilling (1 to 5 ml extra) in 70% of patients.
Implantation depth averaged 22.3 +/- 12.4% at the noncoronary cusp and 20.7 +/-
9.9% at the left coronary cusp. New left bundle branch block occurred in 17%, and
6.3% required new permanent pacemakers. Thirty-day echocardiography showed mild
PVL in 22.3%, 6.9% moderate, and none severe. There was no annular rupture or
coronary obstruction. Mild or greater PVL was associated with larger maximum
annular and left ventricular outflow tract (LVOT) diameters, larger LVOT area and
perimeter, LVOT area greater than annular area, and higher annular eccentricity.
CONCLUSIONS: TAVR with the 29-mm S3 valve beyond the recommended range by
overexpansion is safe, with acceptable PVL and pacemaker rates. Larger LVOTs and
more eccentric annuli were associated with more PVL. Longer term follow-up will
be needed to determine durability of S3 TAVR in this population.
PMID- 29960757
TI - Percutaneous Transhepatic Mitral Valve Repair With the MitraClip System.
PMID- 29960758
TI - Porous CARDIOFORM Septal Occluder Balloons Within the Right Atrial Cavity.
PMID- 29960759
TI - Substance P and the neurokinin-1 receptor in the ischaemic heart: Two sides to
the coin.
PMID- 29960760
TI - High rate of death in patients with atrial fibrillation -Results from EORP-AF
Pilot General Registry.
PMID- 29960761
TI - Is CRT response rate all about patient selection?
PMID- 29960762
TI - Risk factors for early death in primary malignant cardiac tumors: An analysis of
over 40 years and 500 patients.
AB - OBJECTIVES: To investigate risk factors contributing to early death in patients
diagnosed with primary malignant cardiac tumors (PMCTs) and derive better
understanding of these poorly characterized individuals. METHOD: Data from the
Surveillance, Epidemiology and End-Results (SEER) registries on 564 patients
diagnosed with PMCTs between 1973 and 2014 were analyzed. Early death was defined
as survival of <=3 months from the time of diagnosis. Two-tailed chi2 or fisher's
exact test were used for association between categorical variables and occurrence
of early death. Logistic regression analysis was used to assess independent risk
factors of early death. Time trends in early death rates of PMCTs were described
using scatter plot. RESULTS: Of the 564 patients with PMCTs, early death was
identified in 214 individuals (37.9%). Patients with unspecified soft tissue
sarcomas and blood vessel tumors had the highest risk of early death. Age > 80
years and non-consent for surgery were strong predictors of early death in all
PMCT subtypes. In sarcomas, disadvantaged income was associated with an increase
in early mortality, while black race was associated with a reduction in early
mortality. In mesotheliomas and others, male sex was a risk factor for early
mortality, while Hispanic ethnicity was associated with a reduction in early
mortality. Percentages of early death slightly decreased over the past 40 years.
CONCLUSIONS: Predictors of early death are primarily related to age older than 80
years, no surgery and specific histopathology types but also include
disadvantaged socioeconomic status and male sex. Initiatives to identify those at
risk and develop preventive interventions should be prioritized.
PMID- 29960763
TI - Impact of antihypertensive agents on arterial stiffness in hypertensive patients.
AB - AIMS: The present network meta-analysis was performed to comprehensively compare
the ability of different types of antihypertensive agents to ameliorate arterial
stiffness in hypertensive patients. METHODS AND RESULTS: To conduct this network
meta-analysis, we searched PubMed, the Embase database, and the
https://clinicaltrials.gov/ website for all relevant articles concerning clinical
trials on hypertension therapy. The last search date was 10 August 2017. As a
result, 28 eligible articles were enrolled in our meta-analysis. According to the
included studies, there was no significant difference in pulse wave velocity
(PWV) between these treatments. The eight types of antihypertension agents
outperformed placebo in controlling systolic blood pressure (SBP). Angiotensin
converting enzyme inhibitor (ACEI) outperformed angiotensin II receptor blocker
(ARB) in SBP; and angiotensin receptor-neprilysin inhibitor (ARNI) outperformed
diuretic (D)in SBP. CONCLUSIONS: This study found that the eight antihypertensive
agents show obvious effect on reducing SBP other than arterial stiffness.
PMID- 29960764
TI - The Impact of Being Born Preterm or Small for Gestational Age on Early Vascular
Aging in Adolescents.
AB - OBJECTIVE: To assess the impact of being born preterm or small for gestational
age (SGA) on early vascular aging (EVA) in a cohort of healthy Tyrolean
adolescents. STUDY DESIGN: This study is part of an ongoing clinical trial, EVA
Tyrol, a regional cohort study being conducted in western Austria. EVA was
assessed in adolescents (mean age, 16 years) by means of carotid-femoral pulse
wave velocity (PWV), carotid intima-media thickness (cIMT), and blood pressure
measurements. Adolescents were grouped as either term or preterm. Subsequently,
being born SGA was taken into consideration in subgroup analysis. Complete data
on gestational age and birth weight were available for 930 adolescents. RESULTS:
Systolic blood pressure and diastolic blood pressure were significantly higher in
the preterm (mean gestational age, 34.8 +/- 2.3 weeks) and appropriate for
gestational age (AGA) group than in the term and AGA group (P < .05). This
finding remained significant in linear regression analysis after adjustment for
covariables in all models. PWV was significantly higher in the term-SGA group
than in the term-AGA group (6.67 +/- 1.73 m/s vs 6.07 +/- 1.09 m/s; P < .05). In
the linear regression analysis, this finding remained significant in all models.
There were no differences in cIMT between study groups. CONCLUSION: Being born
preterm or SGA might render persons susceptible to EVA. Long-term follow-up of
preterm and SGA individuals is warranted to confirm these results.
PMID- 29960765
TI - Neurocognitive and Health Correlates of Overweight and Obesity among Ten-Year-Old
Children Born Extremely Preterm.
AB - OBJECTIVE: To assess the relationship between overweight (body mass index [BMI]
percentile >=85 and <95) and obesity (BMI >=95 percentile) and developmental and
health outcomes at 10 years of age in a cohort of individuals born extremely
preterm. STUDY DESIGN: This was an observational cohort study of children born
extremely preterm and then assessed at age 10 years for neurocognitive function
and parent-reported behavior and health outcomes. Participants included 871
children aged 10 years. To describe the strength of association between
overweight or obesity and outcomes, we used logistic regression models adjusting
for confounders. Neurocognitive function, academic achievement, parent-reported
health outcome surveys, and height and weight were measured. RESULTS: BMI
category at 10 years of age was not associated with differences in intelligence,
language, or academic achievement. Parents of children with obesity were more
likely to report their child had asthma (OR 2.2; 95% CI 1.4-3.5), fair/poor
general health (OR 3.2; 95% CI 1.4-7.5), and decreased physical function (OR 1.7;
95% CI 1.1-2.9) but less likely to have physician diagnosed attention
deficit/hyperactivity disorder (OR 0.5; 95% CI 0.3-0.97) or an individualized
education plan (OR 0.6; 95% CI 0.4-0.99). CONCLUSION: Among children born
extremely preterm, an elevated BMI, compared with normal or low BMI, is not
associated with a difference in neurocognitive function. However, asthma,
fair/poor general health, and decreased physical function were more prevalent
among study participants with obesity, and attention-deficit/hyperactivity
disorder and individualized education plan were less prevalent.
PMID- 29960767
TI - Acceptability of Multiple Uncoated Minitablets in Infants and Toddlers: A
Randomized Controlled Trial.
AB - OBJECTIVES: To assess the acceptability and swallowability of several minitablets
when administered as a unit dose compared with an equivalent dose of syrup in
children aged 6 months to 5 years. STUDY DESIGN: The acceptability and
swallowability of multiple drug-free minitablets in comparison with glucose syrup
was assessed in 372 children of 2 age groups (186 in age group 1 [6-23 months of
age] and 186 in age group 2 [2-5 years of age]) in a randomized, 3-way, single
administration cross-over study. Age group 1 received 25 minitablets, 100
minitablets, and 5 mL syrup. Age group 2 received 100 minitablets, 400
minitablets, and 10 mL syrup. RESULTS: Superiority was demonstrated in age group
1 for acceptability (25 minitablets, P < .017; 100 minitablets, P < .0001) and
swallowability (25 minitablets and 100 minitablets, both P < .0001) compared with
syrup. In age group 2, noninferiority of acceptability was found only for 400
minitablets (P < .0003), not for 100 minitablets. Subgroup analysis revealed a
strong sequential effect. For swallowability, noninferiority could be
demonstrated for 100 minitablets (P < .01) but not for 400 minitablets.
CONCLUSIONS: Administration of >=25 minitablets is well-tolerated, feasible, and
safe in children aged from 6 months, and was superior to the equivalent dose of
syrup. Children aged >1 year accept <=400 minitablets even better than the
equivalent dose of syrup. Minitablets open the perspective for introducing small
sized solid drug formulations for all children, thus, further shifting the
paradigm from liquid toward small-sized solid drug formulations. TRIAL
REGISTRATION: German Clinical Trials Register (DRKS): DRKS00008843.
PMID- 29960766
TI - Pre-, Perinatal, and Parental Predictors of Body Mass Index Trajectory
Milestones.
AB - OBJECTIVE: To assess associations of pre-, perinatal, and parental factors with
age and magnitude at body mass index (BMI) peak and rebound. STUDY DESIGN: Among
1681 children with BMI data from birth to mid-childhood in Project Viva, we
fitted individual BMI trajectories using mixed-effect models with natural cubic
spline functions and estimated age and magnitude at peak in infancy and rebound
in early childhood. We used stepwise multivariable regression to identify
predictors of peak and rebound in the 1354 (63.6%) children with estimable
trajectory milestones. RESULTS: The mean (SD) of age at BMI peak was 8.4 (2.7)
months and at rebound was 59.8 (19.6) months, and the mean (SD) of magnitude at
peak was 18.0 (1.4) kg/m2 and at rebound was 15.9 (1.2) kg/m2. Girls had a later
age at peak, earlier age at rebound, and lower magnitudes at peak and rebound
than boys. Maternal isolated hyperglycemia (vs normoglycemia: beta 0.7 months
[95% CI 0.2-1.2]) and pre-eclampsia (vs normal blood pressure: 1.6 months [0.8
2.4]) were associated with a later peak, and impaired glucose tolerance (vs
normoglycemia: -0.5 kg/m2 [-0.9, -0.1]) was associated with a lower magnitude at
peak. Greater maternal first-trimester weight gain, smoking during pregnancy, no
breastfeeding, parental obesity, and no university education were associated with
greater BMI at rebound. CONCLUSIONS: We have identified modifiable prenatal and
parental predictors of BMI peak in infancy and rebound in childhood. Early-life
interventions that address these factors may be effective in changing BMI peak
and rebound and potentially preventing later obesity.
PMID- 29960768
TI - Presenting Signs and Symptoms do not Predict Aspiration Risk in Children.
AB - OBJECTIVES: To determine if any presenting symptoms are associated with
aspiration risk, and to evaluate the reliability of clinical feeding evaluation
(CFE) in diagnosing aspiration compared with videofluoroscopic swallow study
(VFSS). STUDY DESIGN: We retrospectively reviewed records of children under 2
years of age who had evaluation for oropharyngeal dysphagia by CFE and VFSS at
Boston Children's Hospital and compared presenting symptoms, symptom timing, and
CFE and VFSS results. We investigated the relationship between symptom presence
and aspiration using the Fisher exact test and stepwise logistic regression with
adjustment for comorbidities. CFE and VFSS results were compared using the
McNemar test. Intervals from CFE to VFSS were compared using the Student t test.
RESULTS: A total of 412 subjects with mean (+/-SD) age 8.9 +/- 6.9 months were
evaluated. No symptom, including timing relative to meals, predicted aspiration
on VFSS. This lack of association between symptoms and VFSS results persisted
even in the adjusted multivariate model. The sensitivity of CFE for predicting
aspiration by VFSS was 44%. Patients with a reassuring CFE waited 28.2 +/- 8.5
days longer for confirmatory VFSS compared with those with a concerning CFE (P <
.05). CONCLUSIONS: Presenting symptoms are varied in patients with aspiration and
cannot be relied upon to determine which patients have aspiration on VFSS. The
CFE does not have the sensitivity to consistently diagnose aspiration so a VFSS
should be performed in persistently symptomatic patients.
PMID- 29960769
TI - Surgical resection as an adjuvant to tyrosine kinase inhibitors in metastatic
GIST: Association or causation?/Are we any closer to an answer?
PMID- 29960770
TI - Oncologic treatment strategies and relative survival of patients with stage I-III
rectal cancer - A EURECCA international comparison between the Netherlands,
Belgium, Denmark, Sweden, England, Ireland, Spain, and Lithuania.
AB - INTRODUCTION: The aim of this EURECCA international comparison is to compare
oncologic treatment strategies and relative survival of patients with stage I-III
rectal cancer between European countries. MATERIAL AND METHODS: Population-based
national cohort data from the Netherlands (NL), Belgium (BE), Denmark (DK),
Sweden (SE), England (ENG), Ireland (IE), Spain (ES), and single-centre data from
Lithuania (LT) were obtained. All operated patients with (y)pTNM stage I-III
rectal cancer diagnosed between 2004 and 2009 were included. Oncologic treatment
strategies and relative survival were calculated and compared between
neighbouring countries. RESULTS: We included 57,120 patients. Treatment
strategies differed between NL and BE (p < 0.001), DK and SE (p < 0.001), and ENG
and IE (p < 0.001). More preoperative radiotherapy as single treatment before
surgery was administered in NL compared with BE (59.7% vs. 13.1%), in SE compared
with DK (55.1% vs. 10.4%), and in ENG compared with IE (15.2% vs. 9.6%). Less
postoperative chemotherapy was given in NL (9.6% vs. 39.1%), in SE (7.9% vs.
14.1%), and in IE (12.6% vs. 18.5%) compared with their neighbouring country. In
ES, 55.1% of patients received preoperative chemoradiation and 62.3%
postoperative chemotherapy. There were no significant differences in relative
survival between neighbouring countries. CONCLUSION: Large differences in
oncologic treatment strategies for patients with (y)pTNM I-III rectal cancer were
observed across European countries. No clear relation between oncologic treatment
strategies and relative survival was observed. Further research into selection
criteria for specific treatments could eventually lead to individualised and
optimal treatment for patients with non-metastasised rectal cancer.
PMID- 29960771
TI - Short communication: Comparison of growth kinetics at different temperatures of
Streptococcus macedonicus and Streptococcus thermophilus strains of dairy origin.
AB - Within the genus Streptococcus, S. thermophilus and S. macedonicus are the 2
known species related to foods. Streptococci are widely used as starter cultures
to rapidly lower milk pH. As S. macedonicus has been introduced quite recently,
much less information is available on its technological potential. Because
temperature is an important factor in fermented food production, we compared the
growth kinetics over 24 h of 8 S. thermophilus and 7 S. macedonicus strains
isolated from various dairy environments in Italy, at 4 temperatures, 30 degrees
C, 34 degrees C, 37 degrees C and 42 degrees C. We used the Gompertz model to
estimate the 3 main growth parameters; namely, lag phase duration (lambda),
maximum growth rate (umax), and maximum cell number at the stationary phase
(Nmax). Our results showed significant differences in average growth kinetics
between the 2 species. Among the strains tested, 37 degrees C appeared to be the
optimal temperature for the growth of both species, particularly for S.
macedonicus strains, which showed mean shorter lag phases and higher cell numbers
compared with S. thermophilus. Overall, the growth curves of S. macedonicus
strains were more similar to each other whereas S. thermophilus strains grew very
differently. These results help to better define and compare technological
characteristics of the 2 species, in view of the potential use of S. macedonicus
in place of S. thermophilus in selected technological applications.
PMID- 29960772
TI - Effects of supplementing rumen-protected niacin on fiber composition and
metabolism of skeletal muscle in dairy cows during early lactation.
AB - Nicotinic acid (NA) has been shown to induce muscle fiber switching toward
oxidative type I fibers and a muscle metabolic phenotype that favors fatty acid
(FA) utilization in growing rats, pigs, and lambs. The hypothesis of the present
study was that supplementation of NA in cows during the periparturient phase also
induces muscle fiber switching from type II to type I fibers in skeletal muscle
and increases the capacity of the muscle to use free FA, which may help to reduce
nonesterified fatty acid (NEFA) flow to the liver, liver triglyceride (TG)
accumulation, and ketogenesis. Thirty multiparous Holstein dairy cows were
allocated to 2 groups and fed a total mixed ration without (control group) or
with ~55 g of rumen-protected NA per cow per day (NA group) from 21 d before
expected calving until 3 wk postpartum (p.p.). Blood samples were collected on d
21, -14, -7, 7, 14, 21, 35, and 63 relative to parturition for analysis of TG,
NEFA, and beta-hydroxybutyrate. Muscle and liver biopsies were collected on d 7
and 21 for gene expression analysis and to determine muscle fiber composition in
the musculus semitendinosus, semimembranosus, and longissimus lumborum by
immunohistochemistry, and liver TG concentrations. Supplementation of NA did not
affect the proportions of type I (oxidative) or the type II:type I ratio in the 3
muscles considered. A slight shift from glycolytic IIx fibers toward oxidative
glycolytic fast-twitch IIa fibers was found in the semitendinosus, and a tendency
in the longissimus lumborum, but not in the semimembranosus. The transcript
levels of the genes encoding the muscle fiber type isoforms and involved in FA
uptake and oxidation, carnitine transport, tricarboxylic acid cycle, oxidative
phosphorylation, and glucose utilization were largely unaffected by NA
supplementation in all 3 muscles. Supplementation of NA had no effect on plasma
TG and NEFA concentrations, liver TG concentrations, and hepatic expression of
genes involved in hepatic FA utilization and lipogenesis. However, it reduced
plasma beta-hydroxybutyrate concentrations in wk 2 and 3 p.p. by 18 and 26% and
reduced hepatic gene expression of fibroblast growth factor 21, a stress hormone
involved in the regulation of ketogenesis, by 74 and 56%. In conclusion, a high
dosage of rumen-protected NA reduced plasma beta-hydroxybutyrate concentrations
in cows during early lactation, but failed to cause an alteration in muscle fiber
composition and muscle metabolic phenotype.
PMID- 29960773
TI - Methylglyoxal: A newly detected and potentially harmful metabolite in the blood
of ketotic dairy cows.
AB - Ketosis causes serious economic losses for the modern dairy industry because it
is a highly prevalent metabolic disease among cows in high-producing herds during
the transition period. Due to some striking similarities between diabetes in
humans and ketosis in dairy cows, there is potential for the use of methylglyoxal
(MGO)-commonly used in human diabetics-as a biomarker in dairy cattle. However,
currently no data are available about the presence of MGO in the serum of dairy
cattle or about the characteristics of its production or its potential
contribution in the pathogenesis of ketosis. To determine the potential origin
and pathway of formation of MGO, cows in different metabolic conditions [i.e.,
non-subclinically ketotic dairy cows in early lactation (n = 7), subclinically
ketotic dairy cows in early lactation (n = 8), overconditioned dry cows (BCS
>4.25, n = 6), and nonlactating heifers (n = 6)] were selected. Serum MGO
concentrations were determined and correlated with indicators of the glucose and
lipid metabolism and with haptoglobin (Hp) as an inflammatory marker. The serum
MGO concentrations in subclinically ketotic cows (712.60 +/- 278.77 nmol/L) were
significantly greater than in nonlactating heifers (113.35 +/- 38.90 nmol/L),
overconditioned dry cows (259.71 +/- 117.97 nmol/L), and non-subclinically
ketotic cows (347.83 +/- 63.56 nmol/L). In serum of lactating cows,
concentrations of glucose and fructosamine were lower than in heifers and were
negatively correlated with MGO concentrations. Even so, concentrations of
metabolic and inflammatory markers such as dihydroxyacetone phosphate,
nonesterified fatty acids, beta-hydroxybutyrate, acetone, and Hp were remarkably
higher in subclinically ketotic cows compared with nonlactating heifers; these
metabolites were also positively correlated with MGO. In human diabetics elevated
MGO concentrations are stated to originate from both hyperglycemia and the
enhanced lipid metabolism, whereas higher MGO concentrations in subclinically
ketotic cows were not associated with hyperglycemia. Therefore, our data suggest
MGO in dairy cows to be a metabolite produced from the metabolization of acetone
within the lipid metabolization pathway and from the metabolization of
dihydroxyacetone phosphate. Furthermore, the highly positive correlation between
MGO and Hp suggests that this reactive compound might be involved in the
proinflammatory state of subclinical ketosis in dairy cows. However, more
research is needed to determine the potential use of MGO as a biomarker for
metabolic failure in dairy cows.
PMID- 29960774
TI - Effect of modified atmosphere packaging on the growth of spoilage microorganisms
and Listeria monocytogenes on fresh cheese.
AB - Queso Fresco has a limited shelf life and has been shown to support the rapid
growth of Listeria monocytogenes during refrigerated storage. In addition to
improving quality and extending shelf life, modified atmosphere packaging (MAP)
has been used to control the growth of pathogenic microorganisms in foods. The
objectives of this study were to determine the effects of MAP conditions on the
survival and growth of spoilage microorganisms and L. monocytogenes during
storage of Queso Fresco manufactured without starter cultures. For L.
monocytogenes experiments, cheeses were surface inoculated at ~4 log10 cfu/g
before packaging. Inoculated and uninoculated (shelf life experiments) cheeses
were placed in 75-um high-barrier pouches, packaged under 1 of 7 conditions
including air, vacuum, or combinations of N2 and CO2 [100% N2 (MAP1), 30% CO2:70%
N2 (MAP2), 50% CO2:50% N2 (MAP3), or 70% CO2:30% N2 (MAP4), 100% CO2 (MAP5)], and
stored at 7 degrees C. Samples were removed weekly through 35 d of storage.
Listeria monocytogenes counts were determined for inoculated samples.
Uninoculated samples were assayed for mesophilic and psychrotolerant counts,
lactic acid bacteria, coliforms, and yeast and mold. In general, cheeses packaged
under conditions consisting of higher contents of CO2 had lower pH levels during
storage compared with those stored in conditions with lower levels or no CO2 at
all. Similarly, the antimicrobial efficacy of MAP in controlling spoilage
microorganisms increased with increasing CO2 content, whereas conditions
consisting of 100% N2, vacuum, or air were less effective. Mean L. monocytogenes
counts remained near inoculation levels for all treatments at d 1 but increased
~2 log10 cfu/g on cheeses packaged in air, vacuum, and 100% N2 (MAP1) conditions
at d 7 and an additional ~1.5 log10 cfu/g at d 14 where they remained through 35
d. In contrast, treatments consisting of 70% CO2 (MAP4) and 100% CO2 (MAP5)
limited increases in mean L. monocytogenes counts to <1 log10 cfu/g through 14 d
and ~1.5 log10 cfu/g by d 21. Mean L. monocytogenes counts increased to levels
significantly higher than inoculation (d 0) on cheeses stored in MAP2 and MAP3 on
d 21, on d 28 for MAP4, and on d 35 for cheeses stored under MAP5 conditions.
Overall, significant treatment * time interactions were observed between air,
vacuum, and MAP1 when each was compared with MAP2, MAP3, MAP4, and MAP5. These
data demonstrate that packaging fresh cheese under modified atmospheres
containing CO2 may be a promising approach to extend shelf life while limiting L.
monocytogenes growth during cold storage.
PMID- 29960775
TI - Short communication: Chronology of different sexual behaviors and motion activity
during estrus in dairy cows.
AB - In studying the efficiency of a variety of methods for estrus detection in a
large dairy herd, we suspected a definite sequence of estrus signs. Consequently,
we observed a subset of animals continuously between 0400 and 2400 h, making a
note of the precise timing and frequency of each sexual behavior. Sixteen
Holstein-Friesian cows, >20 d postpartum, were equipped with motion activity
sensing neck collars and had milk progesterone profiles monitored simultaneously.
The duration between the first and last observed estrus behavior was (mean +/-
SE) 14.0 +/- 1.9 h, with a range 8.5 to 28.75 h. The duration of standing to be
mounted (STBM) was 4.68 +/- 1.49 h, with a range of 0.25 to 18.25 h. Sniffing the
vulva of another cow occurred on average 5.5 +/- 1.3 h (range = 0.25-18.25 h)
before the first STBM. By ranking the first appearance of each behavior, we
established that sniffing was followed by the active behaviors of mounting
another cow and not accepting a mount, as well as the passive behaviors of being
sniffed and STBM by another cow. Chin resting occurred before not accepting a
mount and STBM. All these behaviors were observed in the reverse order after the
last STBM. The mean profile of motion activity revealed an increase in motion
activity with the onset of exploratory behaviors, and highest values occurred
within the period of STBM. Such distinct behavioral sequences may be controlled
by changes in peripheral progesterone and estradiol concentrations, as well as by
subtle independent mechanisms via pheromones in differing concentrations or
divergent composition.
PMID- 29960776
TI - Milk replacer restriction during early life impairs the live body weight and
progesterone patterns of ewe lambs during the replacement period.
AB - Nutritional programming caused by feed restriction during the early life may
counteract the profitability of the dairy sheep farm. However, most studies have
been focused exclusively on the prenatal period, and scarce information regarding
the effect of milk replacer (MR) restriction on feed efficiency [residual feed
intake (RFI)] and progesterone patterns of replacement ewe lambs is available.
Therefore, in the present study 40 Assaf female newborn lambs were penned
individually and assigned randomly to 1 of 2 treatment groups (n = 20 per
treatment). The first group of lambs was fed MR ad libitum (ADLB), whereas the
second one (restricted, RES) only received approximately 62.5% of the MR intake
measured in the ADLB group. All the lambs were weighed twice a week until they
were 35 d old. Then 8 lambs from each group were killed and a morphological study
of the gut was performed. Moreover, a piece of liver was cut to measure fat
content and oxidative status. The rest of the ewe lambs (24) were weaned and
offered a total mixed ration ad libitum to calculate the RFI during the
replacement phase. Plasma samples were collected when ewe lambs were 8 mo old to
perform a nontargeted metabolomic analysis on a hybrid quadrupole-time-of-flight
mass spectrometer coupled to an ultra-high-performance liquid chromatographic
system. Progesterone was also measured weekly on serum samples by sequential
competitive immunoassay until the end of the experiment (9.5 mo old). The results
observed indicate that moderated MR restriction promoted differences in the
morphology of the gut of the 35-d-old lambs, but not in the apparent
digestibility or feed efficiency traits (RFI) during the replacement phase.
However, there was a trend toward reduced live body weight of the RES ewe lambs
when they were 9.5 mo old. Moreover, progesterone patterns revealed that only 1
RES versus 4 ADLB ewe lambs had ovulated for the first time at the end of the
experiment. This evidence suggests the existence of long-term effects caused by
early feed restriction with negative consequences on live body weight and
reproductive traits of replacement ewe lambs.
PMID- 29960777
TI - Genetic parameters of different measures of somatic cell counts in the Rendena
breed.
AB - The objective of this study was to consider different and alternative methods of
using somatic cell count (SCC) data recorded according to the Italian official
milk recording system, estimating its genetic parameters and the correlations
with the yield traits (milk, fat, and protein) in the Rendena breed. The SCC
traits defined for genetic evaluation were somatic cell score, log of the total
daily SCC (LTSCC, i.e., SCC multiplied by daily milk yield) individually recorded
in a day of official control, and 3 different thresholds (>=80,000, >=150,000,
and >=400,000 cells/mL) for somatic cells. A total of 187,052 test-day monthly
records of milk, fat, and protein yields and SCC belonging to 11,718 cows were
used to estimate heritability and genetic correlations between SCC and yield
traits via a bi-trait repeatability test-day model using a Bayesian approach. The
heritability values estimated for the threshold traits ranged from 0.036 to
0.065, less than those observed for monthly somatic cell score and LTSCC traits
that were equivalent to 0.088 and 0.103, respectively. Higher genetic
correlations were estimated between LTSCC trait and all productive traits (0.379
for milk, 0.240 for fat, and 0.370 for protein). The other SCC traits considered
have shown low or almost null genetic correlations with the productive traits
(from 0.008 between fat yield and SCC >=150,000 cells/mL to 0.234 between protein
yield and SCC >=400,000 cells/mL) and almost all estimates included zero in the
95% highest posterior density region interval. These results indicated that
genetic selection for milk, fat, and protein production negatively affects the
LTSCC content and SCC >=400,000 cells/mL but does not negatively influence the
other somatic cell and threshold SCC traits in the Rendena breed. However, the
complete framework of genetic relationships of SCC with all traits under
selection should be considered when deciding on the possible inclusion of SCC in
the breeding program of this small cattle population.
PMID- 29960778
TI - Effect of fibrolytic enzymes on lactational performance, feeding behavior, and
digestibility in high-producing dairy cows fed a barley silage-based diet.
AB - The objectives of this study were to evaluate the effects of pretreating dairy
cow rations with a fibrolytic enzyme derived from Trichoderma reesei (FETR;
mixture of xylanase and cellulase; AB Vista, Wiltshire, UK) on lactation
performance, digestibility, and feeding behavior in response to feeding a barley
silage-based diet. Before starting the dairy trial, in vitro incubations were
conducted to determine whether the addition of FETR would have an effect on these
animal performance characteristics when applied to a barley silage-based diet for
dairy cows. The dairy trial was performed using 8 Holstein dairy cows. The cows
were blocked by parity and assigned randomly to 1 of 4 treatments: 0, 0.5, 0.75,
and 1 mL of FETR/kg of dry matter (DM) diet in a replicated Latin square design.
The pretreatment was applied to the complete diet during the mixing process. The
experimental period continued for 22 d, with each experimental period consisting
of a 16-d adaptation period and a 6-d sampling period. The daily feed intake of
each individual cow was monitored using Insentec feed bins (RIC system, Insentec,
Marknesse, the Netherlands). Feeding behavior characteristics were measured
during the entire sampling period using the feed bin attendance data. Milk
samples were collected in the last 3 d of each experimental period. The addition
of FETR linearly increased the in vitro DM digestibility and tended to improve
the in vitro digestibility of barley silage. There was a cubic effect of the
enzyme levels on the total-tract DM and neutral detergent fiber digestibility.
Maximal digestibility was reached at 0.75 mL of FETR/kg of TMR. The milk fat
yield, fat-corrected milk, and energy-corrected milk quadratically responded to
the incremental levels of FETR. The milk protein percentage linearly improved in
response to FETR. Increasing FETR levels resulted in a quadratic effect on feed
efficiency. There was no effect of FETR level on feeding behavior. In conclusion,
pretreating dairy cow barley silage-based diet with 0.75 mL of FETR/kg of TMR
increased the milk production efficiency of dairy cows fed diet containing 34%
barley silage (DM basis). The positive effect of adding FETR could benefit the
dairy industry in western Canada, where barley silage-based diets are common.
PMID- 29960779
TI - Pegbovigrastim treatment affects gene expression in neutrophils of pasture-fed,
periparturient cows.
AB - Treatment with granulocyte colony-stimulating factor has been reported to
increase circulating neutrophil count and enhance neutrophil function in the
periparturient cow. It was hypothesized that a commercially available recombinant
bovine granulocyte colony-stimulating factor product (pegbovigrastim) affects
gene expression profiles of neutrophils and supports neutrophil function in
periparturient cows. Hence this study was undertaken to analyze expression of
genes involved in neutrophil functions, including migration, interaction with
pathogens, and cell survival. It also assessed the hypothesis that gene
expression profiles in neutrophils are modulated by negative energy balance in
the peripartum period. Holstein-Friesian, Jersey, and mixed-breed cows on pasture
were blocked by expected calving date and body condition score and randomly
assigned in a 2 * 2 factorial design. Cows were fed to exceed energy requirements
prepartum (122%) or restricted to approximately 85% of prepartum energy
requirements. At approximately 7 d before expected calving date, half the cows in
each feed group were randomly assigned to be injected with pegbovigrastim or
saline. Treatments were repeated within 24 h after calving. Blood samples were
collected pretreatment approximately 7 d before calving (d -7). Blood, uterine
flush, and milk samples were collected at 4 (d 4) and 7 d in milk (d 7) to
measure the expression of a panel of 20 genes representing cell adhesion, pattern
recognition, inflammation and cytokine response, antimicrobial capacity, and
apoptosis functions in neutrophils using NanoString technology (NanoString
Technologies Inc., Seattle, WA) to quantify RNA copy numbers. No effects were
observed of prepartum feeding group or a feeding group * treatment interaction
for any of the investigated genes. An effect was observed of time on expression
of several genes in blood neutrophils. After calving, expression of 2 of 4 cell
adhesion-related genes, 3 of 4 pattern recognition receptors, 2 of 4 inflammatory
genes, 2 antimicrobial genes, and 2 of 4 cell survival genes was significantly
greater at d 4 or 7 or both compared with before calving (d -7). Expression of
ICAM1, TLR2, and PTGS2 was significantly higher in blood neutrophils from animals
treated with pegbovigrastim compared with untreated controls, suggesting greater
migration, pattern recognition, and inflammatory response ability. Pegbovigrastim
also affected RNA expression in uterine cells with ICAM1, NOD1, CLEC6A, PTGS2,
MPO, DEFB5, and CATHL6 being expressed at higher levels and SELL, ITGB8, IL8RB,
and IL10 at lower levels. Milk somatic cells showed a similar pattern but with
fewer significant changes. In contrast to the reported decline in neutrophil
function in the transition period, neutrophil gene expression was increased for
many of the genes studied, an apparent attempt to compensate for reduced
neutrophil function. Treatment with pegbovigrastim further increased expression
of several genes involved in these processes in blood neutrophils and changed
uterine cells to a phenotype with increased antimicrobial capacity, typical for
neutrophils that have migrated into their target tissue.
PMID- 29960780
TI - Graduate Student Literature Review: Detecting health disorders using data from
automatic milking systems and associated technologies.
AB - This review synthesizes a range of research findings regarding behavioral and
production responses to health disorders and subsequent illness detection for
herds using automatic (robotic) milking systems (AMS). We discuss the effects of
health disorders on cow behavior and production, specifically those variables
that are routinely recorded by AMS and associated technologies. This information
is used to inform the resultant use of behavior and production variables and to
summarize and critique current illness detection studies. For conventional and
AMS herds separately, we examined research from the past 20 yr and those
variables recorded automatically on-farm that may respond to development of
illness and lameness. The main variables identified were milk yield, rumination
time, activity, and body weight, in addition to frequency of successful, refused,
and fetched (involuntary) milkings in AMS herds. Whether making comparisons
within cow or between sick and healthy cows, consistent reductions in activity,
rumination time, and milk yield are observed. Lameness, however, had obvious
negative effects on milk yield but not necessarily on rumination time or
activity. Finally, we discuss detection models for identifying lameness and other
health disorders using routinely collected data in AMS, specifically focusing on
their scientific validation and any study limitations that create a need for
further research. Of the current studies that have worked toward disease
detection, many data have been excluded or separated for isolated models (i.e.,
fresh cows, certain lactation groups, and cows with multiple illnesses or
moderate cases). Thus, future studies should (1) incorporate the entire lactating
herd while accounting for stage of lactation and parity of each animal; (2)
evaluate the deviations that cows exhibit from their own baseline trajectories
and relative to healthy contemporaries; (3) combine the use of several variables
into health alerts; and (4) differentiate the probable type of health disorder.
Most importantly, no model or software currently exists to integrate data and
directly support decision-making, which requires further research to bridge the
gap between technology and herd health management.
PMID- 29960781
TI - Short communication: Relationships among plasma and milk vitamin B12, plasma free
fatty acids, and blood beta-hydroxybutyrate concentrations in early lactation
dairy cows.
AB - This study was undertaken to evaluate the relationship between plasma and milk
concentrations of vitamin B12 as well as the relationship between plasma or milk
concentrations of vitamin B12 and plasma concentration of free fatty acids (FFA)
or blood concentration of beta-hydroxybutyrate (BHB) of early lactating Ayrshire
(AY) and Holstein (HO) cows. A total of 44 dairy herds (7 AY and 37 HO herds) and
62 AY (21 in first, 19 in second, and 22 in third and more lactations) and 228 HO
(51 in first, 74 in second, and 103 in third and more lactation) cows between 3
and 40 d in milk were involved in the study. Hand-stripped milk samples and blood
samples were taken 6 h after the morning milking. Milk and plasma samples were
analyzed for vitamin B12 concentration and plasma samples were analyzed for FFA
concentration. A handheld device was used for blood BHB concentration
determination. Thresholds for elevated plasma FFA concentration and
hyperketonemia were set at >=0.70 and >=1.2 mmol/L, respectively. Vitamin B12
concentration in milk of AY primiparous cows [2,557 (1,995-3,276) pg/mL] was
lower than in milk from HO primiparous cows [3,876 (3,356-4,478) pg/mL], whereas
no difference was observed among other parities and breeds. Regardless of breeds,
plasma concentration of vitamin B12 of first and second parities was lower than
plasma concentration of third and more lactation cows. Milk vitamin B12
concentration was positively correlated with plasma vitamin B12 concentration,
but the relationship was stronger for AY (rho averaging 0.63) than for HO cows
(rho averaging 0.36). For AY and HO breeds, a significant relationship between
milk or plasma vitamin B12 concentrations and plasma FFA concentration (rho
between 0.29 and 0.59) was observed. Moreover, cows with elevated plasma FFA
concentration had greater milk and plasma vitamin B12 concentrations than cows
with normal plasma FFA concentration. No relationship between vitamin B12
concentration in milk or plasma and blood BHB concentration and hyperketonemia
was noted. In summary, milk is not well correlated with plasma vitamin B12
concentration for HO. It could be hypothesized that elevated plasma concentration
of FFA could have a negative effect on the use of vitamin B12 by cow cells, which
increases the concentration of the vitamin in plasma and its secretion in milk.
PMID- 29960782
TI - Pseudomonas fluorescens group bacterial strains are responsible for repeat and
sporadic postpasteurization contamination and reduced fluid milk shelf life.
AB - Postpasteurization contamination (PPC) of high temperature, short time
pasteurized fluid milk by gram-negative (GN) bacteria continues to be an issue
for processors. To improve PPC control, a better understanding of PPC patterns in
dairy processing facilities over time and across equipment is needed. We thus
collected samples from 10 fluid milk processing facilities to (1) detect and
characterize PPC patterns over time, (2) determine the efficacy of different
media to detect PPC, and (3) characterize sensory defects associated with PPC.
Specifically, we collected 280 samples of high temperature, short time
pasteurized milk representing different products (2%, skim, and chocolate) and
different fillers over 4 samplings performed over 11 mo at each of the 10
facilities. Standard plate count (SPC) as well as total GN, coliform, and
Enterobacteriaceae (EB) counts were performed upon receipt and after 7, 10, 14,
17, and 21 d of storage at 6 degrees C. We used 16S rDNA sequencing to
characterize representative bacterial isolates from (1) test days with SPC
>20,000 cfu/mL and (2) all samples with presumptive GN, coliforms, or EB. Day-21
samples were also evaluated by a trained defect judging panel. By d 21, 226
samples had SPC >20,000 cfu/mL on at least 1 d of shelf life; GN bacteria were
found in 132 of these 226 samples, indicating PPC. Crystal violet tetrazolium
agar detected PPC with the greatest sensitivity. Spoilage due to PPC was
predominantly associated with Pseudomonas (isolated from 101 of the 132 samples
with PPC); coliforms and EB were found in 27 and 37 samples with spoilage due to
PPC, respectively. Detection of Pseudomonas and Acinetobacter was associated with
lower flavor scores; coagulated, fruity fermented, and unclean defects were more
prevalent in d-21 samples with PPC. Repeat isolation of Pseudomonas fluorescens
group strains with identical partial 16S rDNA sequence types was observed in 8
facilities. In several facilities, specific lines, products, or processing days
were linked to repeat product contamination with Pseudomonas with identical
sequence types. Our data show that PPC due to Pseudomonas remains a major
challenge for fluid milk processors; the inability of coliform and EB tests to
detect Pseudomonas may contribute to this. Our data also provide important
initial insights into PPC patterns (e.g., line-specific contamination),
supporting the importance of molecular subtyping methods for identification of
PPC sources.
PMID- 29960783
TI - Effects of milk replacer acidification and free-access feeding on early life
feeding, oral, and lying behavior of dairy calves.
AB - Acidification is a practical way of preserving the bacteriological quality of
milk so that it can be fed to calves under free-access conditions. The objectives
of this study were to evaluate how milk replacer acidification and free-access
feeding affect dairy calf behavior during the first week of life. Sixteen
Holstein male calves were purchased at birth and transported to the University of
Guelph Kemptville Campus Dairy Education and Research Centre. Calves were
randomly assigned to 1 of 4 milk feeding programs: (1) free-access (ad libitum)
feeding of acidified milk replacer (22% crude protein and 17% fat, 150 g/L; FA);
(2) restricted (6 L/d, 150 g/L) feeding of acidified milk replacer (RA); (3) free
access feeding of nonacidified milk replacer (FN); and (4) restricted feeding of
nonacidified milk replacer (RN). Formic acid was used to acidify milk replacer to
a target pH between 4.0 and 4.5. Video recordings of each calf at 1, 2, and 6 d
were analyzed continuously over 24 h for all occurrences of each behavior in the
ethogram. Feeding behavior observations were organized into sucking bouts, from
which feeding behavior outcome variables were calculated. Calves consuming
acidified milk replacer demonstrated more fragmented feeding patterns,
characterized by more pauses within a sucking bout (FA, FN, RA, and RN calves =
12.4, 4.4, 13.7, and 11.9 pauses/bout, respectively) and longer sucking bout
duration (FA, FN, RA, and RN calves = 8.8, 5.2, 9.3, and 8.1 min/bout,
respectively), than calves fed nonacidified milk replacer. Restricted-fed calves
tended to have longer sucking bouts and performed more within-bout sucks (FA, FN,
RA, and RN calves = 10.7, 5.8, 13.5, and 14.1, respectively) and pauses than free
access calves. Acidification and free-access feeding did not affect lying
duration. Calves assigned to the acidified feeding treatments tended to perform
more grooming behavior than those fed nonacidified milk replacer (FA, FN, RA, and
RN calves = 0.9, 0.5, 0.8, and 0.6 h/d, respectively). Free-access feeding did
not affect grooming duration. The observed differences in feeding and grooming
behavior suggest that acidification to a pH between 4.0 and 4.5 may have altered
the palatability of milk replacer. Calves assigned to the acidified milk replacer
feeding treatments did not, however, show avoidance toward this feedstuff during
the first week of life.
PMID- 29960784
TI - Dietary supplement of conjugated linoleic acids or polyunsaturated fatty acids
suppressed the mobilization of body fat reserves in dairy cows at early lactation
through different pathways.
AB - To investigate the metabolic changes in the adipose tissue (AT) of dairy cows
under milk fat depression (MFD), 30 cows were randomly allocated to a control
diet, a conjugated linoleic acid (CLA)-supplemented diet, or a high-starch diet
supplemented with a mixture of sunflower and fish oil (2:1; as HSO diet) from 1
to 112 d in milk. Performance of animals, milk yield, milk composition, energy
balance, and blood metabolites were measured during lactation. Quantitative PCR
analyses were conducted on the AT samples collected at wk 3 and 15 of lactation.
The CLA and HSO diets considerably depressed milk fat yield and milk fat content
at both wk 3 and 15 in the absence of significant changes in milk protein and
lactose contents. In addition, the HSO diet lowered milk yield at wk 15 and
decreased dry matter intake of cows from wk 3 to 15. Compared with the control,
both CLA and HSO groups showed reduced body weight loss, improved energy balance,
and decreased plasma concentrations of nonesterified fatty acids and beta
hydroxybutyrate at early lactation. The gene expression analyses reflected
suppressed lipolysis in AT of the CLA and HSO groups compared with the control at
wk 3, as suggested by the downregulation of hormone-sensitive lipase and fatty
acid binding protein 4 and the upregulation of perilipin 2. In addition, the HSO
diet promoted lipogenesis in AT at wk 15 through the upregulation of 1
acylglycerol-3-phosphate O-acyltransferase 2, mitochondrial glycerol-3-phosphate
acyltransferase, perilipin 2, and peroxisome proliferator-activated receptor
gamma. The CLA diet likely regulated insulin sensitivity in AT as it upregulated
the transcription of various genes involved in insulin signaling, inflammatory
responses, and ceramide metabolism, including protein kinase B2, nuclear factor
kappa B1, toll-like receptor 4, caveolin 1, serine palmitoyltransferase long
chain base subunit 1, and N-acylsphingosine amidohydrolase 1. In contrast, the
HSO diet resulted in little or no change in the pathways relevant to insulin
sensitivity. In conclusion, the CLA and HSO diets induced a shift in energy
partitioning toward AT instead of mammary gland during lactation through the
regulation of different pathways.
PMID- 29960785
TI - Effect of cream aging temperature and agitation on butter properties.
AB - Aging of cream is an important process to manage production time and to produce
butter with consistent quality. The objective of this study was to evaluate the
combined effect of temperature (5, 10, and 15 degrees C) and agitation rate (0,
40, and 240 rpm) during aging of cream on the physical properties of cream and
butter in a model system. Cream's solid fat content (SFC), melting behavior, and
droplet size distribution were measured during and after 90 min of aging. Butter
physical properties such as melting behavior, water content, and hardness were
measured. The effects of agitation on SFC and droplet size are dependent on aging
and churning temperature. Solid fat content increased faster at 5 degrees C, and
the maximum SFC was the highest at this temperature. An effect of agitation on
SFC was observed only when cream was aged at 15 degrees C. Agitating cream at 40
rpm increased the droplet size regardless of aging temperature. Two melting
peaks, medium melting fraction (MMF) and high melting fraction (HMF), were found
in cream samples aged at 5 and 10 degrees C, but only a HMF melting peak was seen
in the cream aged at 15 degrees C. The enthalpy of MMF in the cream aged at 10
degrees C with 40 rpm and without agitation was significantly lower than that in
samples aged at 5 degrees C regardless of agitation rate. Butter can be formed
only from cream aged under certain conditions during 14.5 min of churning, which
are 5 degrees C with high agitation and 10 degrees C regardless of agitation
level. Butter produced with cream aged at 5 degrees C with high agitation showed
significantly higher MMF and total enthalpy values. However, no significant
difference in enthalpy values was observed among the butter samples made from the
cream aged at 10 degrees C. Further crystallization of MMF occurred in the butter
produced with cream aged at 10 degrees C during 24 h of storage at 5 degrees C,
whereas no further crystallization occurred in the butter made with the cream
aged at 5 degrees C with high agitation. The hardest butter was obtained when
cream was aged at 5 degrees C with 240 rpm and at 10 degrees C with 40 rpm.
Softer butter was obtained when cream aged at 10 degrees C with 240 rpm was used.
This butter also had the highest water content. This study shows that butter
hardness can be tailored by changing the aging conditions of the cream. Cream can
be aged at higher temperature with low agitation without altering the hardness of
butter. These results will help dairy producers to optimize butter making
processes to obtain desired properties in the final product.
PMID- 29960786
TI - Adaptation of dairy cows to increasing degrees of incomplete milk removal during
a single milking interval.
AB - Milk accumulation in the udder decreases milk secretion and this effect is
explained as well by the effects of the quantity of milk stored in the udder as
by the duration and repetition of periods of milk stasis. This experiment aimed
to better understand the underlying mechanisms of decreased milk yield in
response to the specific effects of the quantity of milk stored in the udder,
independent from storage duration, on milk yield and composition. Sixteen
Holstein cows were assigned to 4 blocks of 4 cows in a 4 * 4 Latin square design
using 7-d periods, with a 4-d sampling period and a 3-d washout period. Cows were
milked twice daily at approximately 0700 and 1630 h throughout the trial.
Treatments consisted of 4 degrees of milk removal (100, 70, 40, and 0%) applied
at one morning milking, designated M0. Effects of the quantity accumulated were
studied in relation to udder distension, via measurements of the total distance
between the ends of the 4 teats, and cisternal capacity, via the evaluation of
cisternal area by ultrasonographic scan at 1 and 9 h after M0. The effect of the
quantity accumulated was also evaluated in relation to mammary epithelium
permeability by determining plasma lactose concentrations 1 h before and 4, 7,
and 10 h after M0. Leaving milk in the udder at M0 decreased milk production
during the M0-M1 interval in a negative curvilinear manner. As a result, M0+M1
milk yield decreased or tended to decrease significantly by -1.3, -5.3, and -12.8
kg for the 70, 40, and 0% treatments compared with the 100% treatment (41.7 +/-
1.26 kg/d), respectively. Negative carry-over effects on milk yield were observed
until the M3 milking only for the 40 and 0% treatments, and no differences were
observed between the effects of these treatments. The total distance between
teats increased significantly but to decreasing degrees during the M0-M1
interval. For the 40 and 0% treatments, cisternal area, which was increased 1 h
after M0 milking, exhibited no further increase during the M0-M1 interval,
suggesting cisternal distension was close to maximum. Simultaneously, lactose
concentrations increased in blood plasma for only these 2 treatments, and this
increase occurred earlier for the 0% treatment. It was also observed that cows
presenting the earliest increases in plasma lactose concentrations during milk
accumulation lost more milk in response to extended milking intervals.
PMID- 29960787
TI - Effect of alphaS1-casein genotype on phenolic compounds and antioxidant activity
in goat milk yogurt fortified with Rhus coriaria leaf powder.
AB - The aim of this work was to evaluate the phenolic compounds and antioxidant
activity of goat milk yogurt characterized by different alphaS1-casein genotypes
and fortified with Rhus coriaria leaf powder. The alphaS1-casein genotype was
determined by isoelectric focusing, total phenol content was determined by the
Folin-Ciocalteu method, phenolic compounds were identified and quantified by HPLC
UV analysis, and antioxidant activity was measured using 2,2'-azino-bis-3
ethylbenzothiazoline-6-sulfonic acid and ferric-reducing antioxidant power. The
statistical analysis showed a significant effect of the studied factors.
Comparing different genotypes it emerged that yogurt from goats with weak alleles
at CSN1S1 loci (FF) showed the lowest phenolic compounds and therefore a lower
antioxidant activity compared with yogurt from goats with strong alleles at
CSN1S1 loci (AA, BB, AB). Rhus coriaria-fortified yogurt showed a significant
increase in total phenolic compounds and antioxidant activity in comparison with
plain yogurt. The FF-fortified yogurt presented the lowest total phenol content
and antioxidant activity. This could be due to a greater capacity of proteins and
peptides in this yogurt to form stable complexes with phenols. The different
total phenol content detected in R. coriaria-fortified yogurt indicates that the
alphaS1-casein genotype influenced the amount of added phenols that are bound to
the caseins and, therefore, the part that remains free and that affects the
biological capacity of the final product.
PMID- 29960788
TI - Social housing influences the behavior and feed intake of dairy calves during
weaning.
AB - We investigated the effect of social housing on the behavioral, intake, and
physiological changes that occur at weaning for dairy calves fed milk ad libitum.
These changes were evaluated during the weaning (d 40 to 48 of age) and
postweaning (d 49 to 56 of age) stages. Twenty male Holstein calves were fed milk
replacer ad libitum and weaned gradually by dilution over 9 d starting at d 40 of
age. Calves were housed in pairs (10 calves) or individually (10 calves) from
birth until the beginning of the postweaning phase, when all calves were paired.
Feed and water intake were monitored daily. Feeding time was video-recorded, and
blood beta-hydroxybutyrate concentration was measured on alternate days beginning
on d 40 and ending on d 56 of age. Electronic accelerometers continuously
recorded standing and lying behavior for the 17-d study. Solid feed consumption
increased by more than 5-fold over the weaning phase in all calves; during this
phase pair-housed calves consumed more than twice (0.96 vs. 0.50 kg/d on d 48)
that of the individually housed calves. Postweaning all calves rapidly increased
their solid feed intake, and to a greater extent for previously individually
housed calves, such that intake was similar between treatments by d 56. Free
water intake was stable during weaning; however, a decrease (of 6.6 L) occurred
in the constituent milk replacer water intake across this phase. As result, total
water intake (free water + milk replacer water content) decreased (by 6.0 L) over
the weaning phase between d 40 (14.9 L/d) and d 48 (8.9 L/d). On the first day
postweaning (d 49), total water intake for all calves increased sharply (to 19.0
L/d) and then returned to a lower baseline (13.2 L/d) the next day (d 50), and
slowly increased over the following week. During the weaning phase, feeding time
and feeding rate increased with time for all calves, whereas pair-housed calves
had greater feeding rates than individually housed calves (13.4 vs. 6.6 g of
DM/min). After weaning, calves previously housed individually spent more time
feeding in the early hours of the day than calves housed in pairs. Lying time and
lying bout frequency decreased with calf age during the weaning period across
treatments, and pair-housed calves tended to spend less time lying than
individually housed calves (1,015 vs. 1,039 min/d) during this time period. Blood
beta-hydroxybutyrate increased across treatments over the weaning period, with
the largest increase occurring between d 48 (0.05 mmol/L) and d 50 (0.2 mmol/L).
These results show that calves alter their behavioral patterns during weaning and
that housing calves in pairs may ease the transition from milk to solid feed.
PMID- 29960789
TI - Glucocorticoid effects on sheep peripheral blood mononuclear cell proliferation
and cytokine production under in vitro hyperthermia.
AB - The present experiment aimed at understanding the effects of cortisol levels on
sheep peripheral blood mononuclear cell (PBMC) proliferation and cytokine
production during hyperthermia. To mimic stress related to the exposition of high
ambient temperatures, PBMC were cultured at 43 degrees C for 12 h, and
subsequently at 39 degrees C for additional 12 h. Cells in normothermia were
cultured at 39 degrees C for 24 h. Phytohemagglutinin-stimulated PBMC were
cultured with different cortisol levels: 0 ng/mL; 100 ng/mL, representing the
physiological cortisol concentration simulating stress condition (Cort100); and
1,000 ng/mL, representing the hyperactivated hypothalamic-pituitary-adrenal axis
(Cort1000). Phytohemagglutinin-stimulated PBMC with 0 ng/mL of cortisol
concentration represented the positive control, whereas nonstimulated PBMC
without cortisol represented the negative control (NC). The free cell
supernatants were collected for the determination of IL-6, IL-1beta, and IL-10 by
ELISA. Bromodeoxyuridine assay was performed on cells to determine cell
proliferation. Exposition to hyperthermia negatively affected cell proliferation,
IL-6, IL-1beta, and IL-10 concentrations in cell supernatants. The interaction of
hyperthermia and cortisol level affected both cell proliferation and IL-10
production. Both PBMC proliferation and IL-10 production in positive control,
Cort100, and Cort1000 decreased at 43 degrees C as compared with 39 degrees C NC.
On average, the Cort100 treatment displayed higher concentrations of IL-6 than
NC. The present experiment demonstrated that the action of cortisol concentration
simulating stress condition on cell proliferation and cytokine production was a
permissive/stimulatory action during normothermia, whereas it was a suppressive
action during hyperthermia. These data confirmed that cortisol concentration
simulating stress condition could have a role in the immune system of sheep via
mediating cellular homeostasis in the condition of hyperthermia. The negative
effects of hyperthermia on sheep immune responses were apparent when performing
an immunological challenge.
PMID- 29960790
TI - Epidemiology of fatal ruptured aortic aneurysms in the United States (1999-2016).
AB - OBJECTIVE: Ruptured aortic aneurysms (rAAs) are associated with high mortality.
The purpose of this study was to describe the trends of deaths due to rAA in the
United States. METHODS: A retrospective review of the national death certificate
data from the U.S. National Vital Statistics System was done to identify deaths
due to rAAs in the United States between 1999 and 2016. Patients aged 15 years or
older with rAA as the underlying cause of death as defined by International
Classification of Diseases, Tenth Revision codes I71.1 (ruptured thoracic aortic
aneurysm [rTAA]), I71.3 (ruptured abdominal aortic aneurysm [rAAA]), I71.5
(ruptured thoracoabdominal aortic aneurysm), and I71.8 (rAA of unspecified site)
were included and standardized to U.S. Census data. RESULTS: A total of 104,458
deaths due to rAAs occurred during the study period. The overall age-adjusted
incidence of fatal rAA was 23.3 per 1 million (rAAA, 15.1; rTAA, 3.1;
thoracoabdominal, 0.4; and unspecified site, 4.8). The annual incidence of rAA
decreased by 68% from 40.0 (1999) to 12.8 (2016) per 1 million (rTAA by -67% from
5.5 to 1.8 and rAAA by -70% from 26.3 to 7.89 per 1 million; P < .001 for all
comparisons). These trends were consistent across age groups, sexes, and races.
There was a significant seasonal variation in rAA mortality, with higher deaths
in winter months compared with summer months. The incidence of rAA is highest in
Midwest states (27.1 per 1 million), followed by Northeast (23.8 per 1 million)
and West (14 per 1 million) states, and lowest in Southern states (13.6 per 1
million). Only 57% of rAAA deaths occurred in men >=65 years. CONCLUSIONS: The
incidence of fatal rAA, rTAA, and rAAA drastically decreased in the United States
between 1999 and 2016, a trend that was consistent across age groups, sexes, and
races. A significant percentage of fatal rAAAs occurred in patients who are not
eligible for the current screening program.
PMID- 29960791
TI - The role of selective stenting for superior mesenteric artery scallops during
fenestrated endovascular aneurysm repair.
AB - OBJECTIVE: Stenting of small fenestrations of the Zenith fenestrated endograft
(ZFEN; Cook Medical, Bloomington, Ind) is necessary during fenestrated
endovascular aneurysm repair (FEVAR) of complex abdominal aortic aneurysms to
avoid malalignment. However, stenting of superior mesenteric artery (SMA)
scallops of ZFEN devices is optional according to the instructions for use. The
objective of this study was to assess the early and midterm outcomes of selective
use of stents in SMA scallops of ZFEN during FEVAR procedures. METHODS: This
study is a single-institution retrospective review of prospectively enrolled
patients treated at the University of North Carolina at Chapel Hill between July
2010 and August 2014. Only patients with SMA scallops were included for analysis.
We compared results between patients grouped as stented or unstented SMA
scallops. The scallops were stented when one or more of the following criteria
were present: misalignment of scallop determined by balloon testing
intraoperatively; configuration consisting of an SMA scallop and a single renal
fenestration or stent; and pre-existing stenosis in the vessel adjacent to the
graft scallop. The study was approved by the local Institutional Review Board.
Primary outcomes addressed were mortality, vessel patency, early and late
complications, and reintervention rates. Baseline characteristics of the patients
and procedure data were also described. RESULTS: During the 48-month study
period, 61 patients were treated for complex abdominal aortic aneurysms at the
University of North Carolina with a mean age of 73 years, and 74.3% of patients
were male. Thirty-nine of 61 patients (63.9%) had a device design with an SMA
scallop and were included for analysis. Eleven of 39 patients (28%) had the SMA
primarily stented and 28 (72%) were unstented. There was only one death (2.5%)
during the 30-day postoperative period, with 100% technical success and branch
patency. In the unstented group, there were three SMA complications during follow
up, two requiring reintervention; however, there were no associated deaths. Among
the stented group, there was one branch-related complication that occurred during
the procedure but no stent stenosis or occlusion during the long-term follow-up.
During the mean follow-up period of 21.7 months, no SMA stent thrombosis
occurred. There was no statistical difference in outcomes between groups.
CONCLUSIONS: Single-wide SMA scallops of ZFEN during FEVAR procedures may be
selectively stented using specific criteria and rigorous follow-up, without
compromising the safety and efficacy of the SMA.
PMID- 29960792
TI - Early cannulation of bovine carotid artery grafts (Artegraft) after primary
vascular access and fistula revision procedures.
AB - OBJECTIVE: Tunneled dialysis catheter (TDC) use has been associated with
increased infectious complications and mortality in hemodialysis-dependent
patients. Unfortunately, patients who undergo fistula revisions or creation of a
new arteriovenous fistula frequently require a TDC during the postoperative
period. Bovine carotid artery grafts (BCAGs) can be used as an early-access
dialysis conduit to reduce TDC dependence. This study describes the performance
of BCAGs that were cannulated early (<3 days) after implantation and associated
clinical outcomes. METHODS: BCAGs were implanted in 63 consecutive dialysis
dependent patients. Patients and dialysis centers were directly provided early
cannulation instructions; 31 (49%) patients were cannulated early, and of the 31
patients cannulated early, 21 (68%) were cannulated during the first
postoperative day. Early complications, primary patency, secondary patency, and
TDC incidence were monitored through clinic visits, hospital records, and phone
calls to dialysis centers. RESULTS: The primary patency of BCAGs at 1 year in the
early and late cannulation cohorts was 28% and 39%, respectively. The secondary
patency of BCAGs at 1 year in the early and late cannulation cohorts was 74% and
77%, respectively. Early complications occurred in 11 (19%) patients who received
a BCAG. There were no significant differences in complication rates between early
and late cannulation patients. Of the 24 patients who underwent the operation
without a pre-existing TDC, only three (13%) required TDC placement during the 30
day postoperative period. CONCLUSIONS: BCAGs can be cannulated early without
increased complication rates or a negative impact on midterm patency. Early
cannulation of BCAGs obviates the need for a TDC postoperatively in dialysis
dependent patients undergoing primary vascular access or fistula revision
procedures.
PMID- 29960793
TI - Impact of external carotid artery occlusion at declamping of the external and
common carotid arteries during carotid endarterectomy on development of new
postoperative ischemic cerebral lesions.
AB - OBJECTIVE: The external carotid artery (ECA) is inadvertently occluded during
carotid endarterectomy (CEA). The importance of ECA occlusion has been emphasized
as a loss of extracranial to intracranial collaterals, a source of chronic
embolization, or a site for extended thrombosis during wound closure. This study
aimed to determine whether ECA occlusion that inadvertently developed during
endarterectomy and that was eventually detected using blood flow measurement of
the ECA after declamping of all carotid arteries is a risk factor for development
of new postoperative ischemic lesions at declamping of the ECA and common carotid
artery (CCA) while clamping the internal carotid artery (ICA). This study also
aimed to determine whether intraoperative transcranial Doppler (TCD) monitoring
predicts the risk for development of such lesions. METHODS: This was a
prospective observational study that included patients undergoing CEA for severe
stenosis (>=70%) of the cervical ICA. When blood flow through the ECA measured
using an electromagnetic flow meter decreased rapidly on clamping of only the ECA
before carotid clamping for endarterectomy and was not changed by clamping of
only the ECA after carotid declamping following endarterectomy, the patient was
determined to have developed ECA occlusion. These patients underwent additional
endarterectomy for the ECA. TCD monitoring in the ipsilateral middle cerebral
artery was also performed throughout surgery to identify microembolic signals
(MESs). Brain magnetic resonance diffusion-weighted imaging (DWI) was performed
before and after surgery. RESULTS: There were 104 patients enrolled in the study.
Eight patients developed ECA occlusion during surgery. The incidence of
intraoperative ECA occlusion was significantly higher in patients without MESs at
the phase of ECA and CCA declamping (8/12 [67%]) than in those with MESs (0/92
[0%]; P < .0001). Six patients exhibited new postoperative ischemic lesions on
DWI. The incidence of intraoperative ECA occlusion (P < .0001) and the absence of
MESs at declamping of the ECA and CCA while clamping the ICA (P <. 0001) were
significantly higher in patients with development of new postoperative ischemic
lesions on DWI than in those without. Sensitivity and specificity for the absence
of MESs at declamping of the ECA and CCA while clamping the ICA for predicting
development of new postoperative ischemic lesions on DWI were 100% (6/6) and 94%
(92/98), respectively. CONCLUSIONS: ECA occlusion at declamping of the ECA and
CCA while clamping the ICA during CEA is a risk factor for development of new
postoperative ischemic lesions. Intraoperative TCD monitoring accurately predicts
the risk for development of such lesions.
PMID- 29960794
TI - Fascial suture technique versus open femoral access for thoracic endovascular
aortic repair.
AB - BACKGROUND: Fascial suture technique (FST) has proved to be a safe and effective
access closure technique after endovascular repair of the abdominal aorta. FST
has not yet been investigated for closure of large-bore access after thoracic
endovascular aortic repair (TEVAR). The aim of this study was to compare FST with
open femoral access in terms of access safety, hemostasis efficacy, and
reintervention rate after TEVAR. METHODS: A retrospective study including
consecutive patients undergoing TEVAR with either FST or open femoral access
between January 2010 and April 2016 was undertaken. Exclusion criteria included
the use of closure devices. The composite primary end point was defined as any
access-related complication (bleeding, femoral artery stenosis or occlusion,
pseudoaneurysm, and wound infection) during 30 postoperative days. Preoperative
and procedural variables were examined in a multiple logistic regression model as
potential associated factors with access morbidity. All access vessels were
postoperatively examined by clinical examination and computed tomography
angiography before discharge as well as during the follow-up period. In case of
suspected pseudoaneurysm, additional duplex ultrasound and computed tomography
angiography confirmed the diagnosis. RESULTS: From a total of 206 patients
undergoing TEVAR, 109 (53%) had FST, whereas 93 (45%) had an open femoral access.
Four patients were excluded: closure device was used in one; one had primary
conversion after percutaneous puncture without FST; and in two, no data were
available about the femoral access. The access complication rate was higher in
FST (FST, 14 [13%]; open access, 3 [3%]; P = .01). Five (4.6%) patients needed
early reintervention, two for bleeding and three for vessel occlusion. Seven
(6.4%) pseudoaneurysms were detected during the 30-day period in the FST group;
three had successful exclusion with thrombin injection, one was treated with
manual compression, one was treated with open repair, and two were managed
conservatively. Four (3.6%) patients in the FST group and three (3%) patients in
the open access group had wound complications. After multiple logistic
regression, FST was the only independent factor for any access complication (odds
ratio, 5.176; 95% confidence interval, 1.402-19.114; P = .014). During follow-up,
neither new pseudoaneurysm nor stenosis or occlusion was detected. CONCLUSIONS:
FST for large-hole closure had higher risk for any access complication compared
with open access in TEVAR during the 30-day postoperative period. No other
complications during 12 months of follow-up were observed in FST patients.
PMID- 29960795
TI - Metabolic Changes of Brain Developmental Venous Anomalies on 18F-FDG-PET.
AB - RATIONALE AND OBJECTIVES: To determine the metabolic effects of developmental
venous anomalies (DVAs) and to correlate those effects with conventional magnetic
resonance imaging (MRI) findings. MATERIALS AND METHODS: We conducted a
retrospective review of MRI and brain 18F-fluorodeoxyglucose positron emission
tomography (18F-FDG-PET) examinations in subjects with DVAs. Conventional MRI was
used to determine DVA number, location, size, and associated parenchymal findings
such as atrophy, hemorrhage, cavernoma, capillary telangiectasia, cortical
dysplasia/polymicrogyria, and white matter signal abnormality. Qualitative and
quantitative measures of relative metabolism in the drainage territory of the DVA
were measured on 18F-FDG-PET. RESULTS: Fifty-four subjects with 57 DVAs were
included in the analysis. 38% were associated with qualitative and quantitative
metabolic abnormalities on 18F-FDG-PET, with decreased metabolism in the
parenchyma surrounding all but one of these DVAs. DVAs draining gray matter were
significantly more likely to be hypometabolic than those draining only white
matter, suggesting that the metabolic effects of DVAs may be underestimated on
18F-FDG-PET. CONCLUSION: Altered metabolism is seen in the drainage territory of
a significant proportion of DVAs, suggesting that these anomalies are vascular
lesions with abnormal physiologic features.
PMID- 29960796
TI - Erratum Regarding "Arteriovenous Fistula Maturation in Prevalent Hemodialysis
Patients in the United States: A National Study" (Am J Kidney Dis. 2018;71[6]:793
801).
PMID- 29960797
TI - Spuriously Low Serum Bicarbonate Levels in Patients With Hyperlipidemia: A Report
of 4 Cases.
AB - Four patients were recently seen at our institution presenting with severe
hypobicarbonatemia and elevated anion gap on serum specimens processed by an
autoanalyzer using enzymatic reactions. Arterial blood gas values in each case
revealed no significant acid-base disturbance and a marked discordance between
arterial blood gas calculated bicarbonate levels and those reported on the basic
metabolic panel. All patients had profound hyperlipidemia (triglycerides >
3,500mg/L), and ultracentrifugation of one patient's serum corrected the
discordance. Lipid interference with the photometric measurement of light
absorbance after enzymatic reaction in the autoanalyzer is thought to be
responsible for the low reported bicarbonate values. Use of an indirect ion
specific electrode method for total carbon dioxide analysis would avoid this
pitfall. Caution is advised when enzymatic autoanalyzer-calculated laboratory
values are used to diagnose acid-base disturbances in patients with severe
hyperlipidemia. Physicians involved in the diagnosis of acid-base disorders in
hospitalized patients should always be aware of the method used by their
chemistry laboratories to determine total carbon dioxide values.
PMID- 29960798
TI - Military applications of soldier physiological monitoring.
AB - Wearable physiological status monitoring is part of modern precision medicine
that permits predictions about an individual's health and performance from their
real-time physiological status (RT-PSM) instead of relying on population-based
predictions informed by estimated human, mission, and environmental/ambient
conditions. RT-PSM systems have useful military applications if they are soldier
acceptable and provide important actionable information. Most commercially
available systems do not address relevant military needs, typically lack the
validated algorithms that make real time computed information useful, and are not
open architected to be integrated with the soldier technological ecology.
Military RT-PSM development requires committed investments in iterative efforts
involving physiologists, biomedical engineers, and the soldier users. Military
operational applications include: (1) technological enhancement of performance by
providing individual status information to optimize self-regulation, workload
distribution, and enhanced team sensing/situational awareness; (2) detection of
impending soldier failure from stress load (physical, psychological, and
environmental); (3) earliest possible detection of threat agent exposure that
includes the "human sensor"; (4) casualty detection, triage, and early clinical
management; (5) optimization of individual health and fitness readiness habits;
and (6) long term health risk-associated exposure monitoring and dosimetry. This
paper is focused on the performance-related applications and considers near term
predictions such as thermal-work limits, alertness and fitness for duty status,
musculoskeletal fatigue limits, neuropsychological status, and mission-specific
physiological status. Each new measurement capability has provided insights into
soldier physiology and advances the cycle of invention, lab and field testing,
new discovery and redesign.
PMID- 29960799
TI - Generation of a broadly reactive influenza H1 antigen using a consensus HA
sequence.
AB - H1N1, one of the most prevalent influenza A virus subtypes affecting the human
population, can cause infections varying from mild respiratory syndrome to severe
pneumonia. The current H1N1 vaccine needs to be updated annually and does not
protect against future outbreaks. Here, we downloaded 2,656 HA protein sequences
of human H1N1 viruses from the NCBI influenza database (up to the date of Aug.
2012) and constructed a phylogenetic tree of these H1 proteins via the neighbor
joining method using MEGA 5.0 software. A consensus H1 protein (CH1) was
generated and was further modified with published conserved T-cell and B-cell
epitopes. Interestingly, this CH1 protein is genetically similar to an H1 isolate
obtained during the 1980s (A/Memphis/7/1980), indicating that a universal HA
antigen may exist in nature. Vaccination with a DNA vaccine expressing CH1
elicited broadly reactive T-cell and B-cell responses to heterologous H1N1
viruses, though this vaccine did not successfully neutralize pdm09 H1N1 viruses.
A combination of CH1 and pdm09 HA in a DNA vaccination neutralized pdm09 H1N1
viruses and protected mice from lethal infections by all representative H1N1
viruses. Moreover, a recombinant chimeric PR8-CH1 virus carrying HA sequence of
the consensus H1 and all other seven genes from the PR8 strain was highly
attenuated in mice, with a lethal dose (LD50) of more than 106 pfu. Vaccination
with PR8-CH1 virus provided complete protection against infections by
heterologous H1N1 strains. Taken together, a universal H1 antigen, CH1, was
developed by constructing a consensus HA sequence, and the PR8-CH1 virus
containing this consensus sequence elicited broadly protective immunity against
heterologous H1N1 viruses.
PMID- 29960800
TI - Immunogenicity and safety of the quadrivalent meningococcal vaccine MenACWY-TT co
administered with a combined diphtheria-tetanus-acellular pertussis vaccine
versus their separate administration in adolescents and young adults: A phase
III, randomized study.
AB - BACKGROUND: This study evaluated the immunogenicity and safety of quadrivalent
meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein
(MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis
vaccine (Tdap) versus their separate administration in adolescents and young
adults. METHODS: In this phase III, randomized, partially-blind study
(NCT01767376), healthy 11-25-year-olds (N = 660) were randomized (1:1:1) to
receive MenACWY-TT and Tdap at Month 0 (Co-ad group), MenACWY-TT at Month 0 and
Tdap at Month 1 (ACWY_Tdap group) or Tdap at Month 0 and MenACWY-TT at Month 1
(Tdap_ACWY group). Immune responses to MenACWY-TT were measured by serum
bactericidal assay using rabbit complement (rSBA). Anti-diphtheria (D), anti
tetanus (T), anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA) and
anti-pertactin (PRN) antibody concentrations were assessed using enzyme-linked
immunosorbent assays. Non-inferiority of immunogenicity was assessed using pre
defined clinical criteria. Safety was also evaluated. RESULTS: Non-inferiority of
immunogenicity of MenACWY-TT and Tdap when co-administered versus their separate
administration was demonstrated in terms of rSBA geometric mean titers (GMTs) for
4 meningococcal serogroups and of the percentage of participants with antibody
concentrations >1 IU/ml for D and T. Among the pertussis antigens, non
inferiority criteria for geometric mean concentrations (GMCs) were reached for
PT, but not met for FHA and PRN. Across all groups, >=93.2% of participants had
vaccine responses to each meningococcal serogroup, >=99.1% were seroprotected
against T and D, and >=85.5% had booster responses to each pertussis antigen.
Robust increases in antibody GMTs/GMCs were observed for all antigens between pre
and post-vaccination. Both vaccines had clinically acceptable safety profiles.
CONCLUSION: Immune responses to MenACWY-TT and to the T and D antigens from Tdap
were not impacted by their co-administration. The lower antibody concentrations
observed against the pertussis components may be of limited clinical relevance
since robust anti-pertussis booster responses were observed. This study supports
concurrent administration of the 2 vaccines in adolescents.
PMID- 29960801
TI - Improving ability of RSV microneutralization assay to detect G-specific and cross
reactive neutralizing antibodies through immortalized cell line selection.
AB - Respiratory syncytial virus (RSV) is a significant cause of bronchiolitis and
pneumonia. Protection against RSV is associated with neutralizing antibodies
against the fusion (F) and attachment (G) glycoproteins. Several RSV vaccine
candidates are in development, but their immunogenicity is hard to compare due to
the little-understood differences between multiple RSV neutralizing antibody
assays used. Existing assays utilize primarily Vero or HEp-2 cells, but their
ability to detect G-neutralizing antibodies or antibodies against specific RSV
strains is unclear. In this work, we developed an RSV microneutralization assay
(MNA) using unmodified RSV and immortalized cell line derived from human airway
epithelial cells (A549). Performance of A549-, HEp-2- and Vero-based MNA was
compared under the same assay conditions (fixed amount of virus and cells) with
regards to detection of neutralizing antibodies against RSV A or B viruses, G
reactive neutralizing antibodies, and effect of complement. Our results indicate
that A549 cells yield the highest MNA titers, particularly in the RSV A/A2 MNA,
are least susceptible to complement-enhancing effect of neutralizing titer
readout and are superior to Vero or HEp-2 MNA at recognizing G-reactive
neutralizing antibodies when no complement is used. Vero cells, however, can be
more consistent at recognizing neutralizing antibodies against multiple RSV
strains. The choice of substrate cells thus affects the outcome of MNA, as some
immortalized cells better support detection of broader range of neutralizing
antibodies, while others facilitate detection of G-targeting neutralizing
antibodies, a long-thought prerogative of primary airway epithelial cells.
PMID- 29960802
TI - Cyclic OmpC peptidic epitope conjugated to tetanus toxoid as a potential vaccine
candidate against shigellosis.
AB - In earlier works we have described that mice immunized with outer membrane
protein OmpC survive the challenge with live Shigella flexnerii 3a. We have also
identified conformational epitope of this protein, that was recognized by mice
antibodies. The aim of current work was to investigate whether synthetic OmpC
epitope homologs can elicit immunological response sufficient in protecting mice
against shigellosis. Several linear peptides containing RYDERY motif were
synthesized and conjugated to poly-lysine. These conjugates appeared to be poor
immunogens and to boost the immunological response an addition of the adjuvant
(MPL) was required. Unfortunately, the MPL alone caused a very high immunological
reaction that was masking response to peptidic epitope. Under those circumstances
we used tetanus toxoid (TT) as the carrier protein for the peptides and the agent
stimulating immunological response. Series of cyclic peptides, homologs of the
OmpC main epitope were synthesized and conjugated to TT. The loop size in cyclic
peptides varied by number of glycine residues, i.e., 1-3 residues added to the
GLNRYDERYIGK motif. The linear GLNRYDERYIGC-TT was also prepared as the control.
The latter conjugate gave the highest immunological response, followed by the
cyclic-GGLNRYDERYIGC-TT and cyclic-GLNRYDERYIGC-TT. The third peptide, cyclic
GGGLNRYDERYIGC-TT, gave a very low response, although it was the most resistant
to proteolysis. However, antibodies obtained against cyclic-GGLNRYDERYIGC-TT were
more potent to recognize both OmpC and Shigella flexnerii 3a cells than the
antibodies against linear GLNRYDERYIGC-TT. Furthermore, the monoclonal antibodies
raised against linear GLNRYDERYIGC-TT showed 20-fold lower dissociation constant
(KD) than the naturally occurring polyclonal antibodies from umbilical cord sera.
Monoclonal antibodies also gave a weaker signal in electron microscope than mice
and human polyclonal antibodies. In overall, our results point to cyclic peptides
as better candidates for a vaccine development, since they are eliciting
production of the higher affinity antibodies against Shigella cells and OmpC.
PMID- 29960803
TI - From aquaporin to ecosystem: Plants in the water cycle.
AB - Vascular plants are major intermediaries in the global water cycle, and are
highly adapted to both facilitate and resist water fluxes, such as during root
uptake, translocation in the xylem, and transpiration by leaves. Here, we
summarize the contributions to a Special Issue on water in the Journal of Plant
Physiology, which cluster around the theme of control and facilitation of water
movement in plants. We conclude with an editorial view of the need for plant
physiologists to consider larger cultural issues surrounding water use,
especially in terms of the increasing agricultural demand for water to produce
animal feed, with its associated trophic nutritive losses and environmental
damage.
PMID- 29960804
TI - A Case of Palpitations Due to T-Wave Oversensing Caused by Sacubitril/Valsartan.
AB - A 58-year-old man with previous mitral/aortic mechanical-valve replacement,
aortic root repair, and coronary disease developed severe left-ventricular
dysfunction following AV-node ablation/single-chamber pacemaker implantation for
management of atrial fibrillation. He then underwent an upgrade to cardiac
resynchronization therapy with a defibrillator. To manage his heart failure
better, angiotensin-receptor blocker therapy was changed to sacubitril/valsartan,
after which symptomatic palpitations with T-wave oversensing occurred. The
resolved T-wave oversensing and palpitations stopped upon discontinuation of
sacubitril/valsartan and recurred upon rechallenge, requiring a switch back to
valsartan monotherapy. Our report presents the first known case of T-wave
oversensing due to sacubitril/valsartan.
PMID- 29960805
TI - Immune Checkpoint Inhibitors: Game Changing Cancer Therapy With a Cardiac Cost.
What Are the Mechanisms and Unresolved Questions in Cardiotoxicity?
PMID- 29960807
TI - Immunoglobulins from sera of antiphospholipid syndrome patients are internalized
in the HTR-8/SVneo cell line and cytotrophoblast in culture.
AB - Women with antiphospholipid syndrome (APS) experience pregnancy complications
mostly due to impaired trophoblast cell functions. Antiphospholipid antibodies
(aPL) affect extravillous trophoblast in vivo and in culture, but the mechanisms
are still poorly understood. Previously, syncytiotrophoblast was shown to bind
and internalize aPL, which was not replicated for extravillous cytotrophoblast in
short term culture. Here, aPL binding and time dependent internalization was
demonstrated with exposure to aPL in the extravillous cell line HTR-8/SVneo and
isolated first trimester of pregnancy cytotrophoblast (CT) using
immunocytochemistry and flow cytometry. Intracellular aPL were detectable from 2
h of culture, reaching 30.7 +/- 3.1% (p < 0.001) positive cells in CT and 24.8 +/
7% (p < 0.01) in HTR-8/SVneo cells at 24 h and 33 +/- 4.2% (p < 0.01) at 48 h.
The data presented show that extravillous trophoblast cells internalize aPL in a
time-dependent manner significantly more than control immunoglobulins after 24 h
of exposure.
PMID- 29960806
TI - Regulation of IL-10 and IL-17 mediated experimental autoimmune encephalomyelitis
by S-nitrosoglutathione.
AB - In this study, we investigated IL-10 and IL-17 specific immunomodulatory
potential of S-nitrosoglutathione (GSNO), a physiological nitric oxide carrier
molecule, in experimental autoimmune encephalomyelitis (EAE). In active EAE
model, GSNO treatment attenuated EAE severity and splenic CD4+ T cells isolated
from these mice exhibited decreased IL-17 expression without affecting the IFN
gamma expression compared to the cells from untreated EAE mice. Similarly,
adoptive transfer of these cells to nave mice resulted in reduction in IL-17
expression in the spinal cords of recipient mice with milder EAE severity. CD4+ T
cells isolated from GSNO treated EAE mice, as compared to untreated EAE mice,
still expressed lower levels of IL-17 under TH17 skewing conditions, but
expressed similar levels of IFN-gamma under TH1 skewing condition. Interestingly,
under both TH17 and TH1 skewing condition, CD4+ T cells isolated from GSNO
treated EAE mice, as compared to untreated EAE mice, expressed higher levels of
IL-10 and adoptive transfer of these TH17 and TH1 skewed cells seemingly
exhibited milder EAE disease. In addition, adoptive transfer of CD4+ T cells from
GSNO treated EAE mice to active EAE mice also ameliorated EAE disease with
induction of spinal cord expression of IL-10 and reduction in of IL-17, thus
suggesting the participation of IL-10 mechanism in GSNO mediated
immunomodulation. GSNO treatment of mice passively immunized with CD4+ T cells
either from GSNO treated EAE mice or untreated mice further ameliorated EAE
disease, supporting efficacy of GSNO for prophylaxis and therapy in EAE. Overall,
these data document a modulatory role of GSNO in IL-17/IL-10 axis of EAE and
other autoimmune diseases.
PMID- 29960808
TI - Patterns of nutrients intakes in relation to glioma: A case-control study.
AB - BACKGROUND & AIMS: Nutrient pattern analysis is an easy way to compare nutrient
intakes across different nations due to the universality of nutrients nature. The
current study aimed to investigate the relation between patterns of nutrients
intake and glioma in a case-control study in Iranian adults. METHODS: In this
hospital-based case-control study, we enrolled 128 pathologically confirmed new
cases of glioma and 256 age and sex-matched controls. Dietary intakes of study
participants were assessed using the validated Block-format 123-item semi
quantitative FFQ. Data on potential confounders were also collected through the
use of pre-tested questionnaire. RESULTS: Four nutrient patterns were identified
through the use of factor analysis. Participants were categorized based on
tertiles of nutrient patterns' scores. Adherence to the first nutrient pattern
was not significantly associated with the odds of glioma (0.93; 0.40-2.15).
Participants with greater adherence to the second nutrient pattern were less
likely to have glioma in crude model (0.48; 0.28-0.83). The inverse association
remained significant after controlling for age, sex and energy intake (0.42; 0.24
0.78). Further controlling for other potential confounders, including BMI,
resulted in the disappearance of the association (0.52; 0.25-1.10). Greater
adherence to the third nutrient pattern was directly associated with the odds of
glioma (1.92; 1.10-3.35). Even after controlling for sex, age and energy intake,
the association was statistically significant (2.83; 1.28-4.21). However, when
other confounders were taken into account, the association became non-significant
(2.28; 0.89-5.82). The fourth nutrient pattern was not associated with the odds
of glioma (0.71; 0.35-1.42). CONCLUSION: We failed to find any significant
independent association between nutrient patterns and odds of glioma. Further
studies needed to confirm these findings.
PMID- 29960809
TI - Effect of vegetarian dietary patterns on cardiometabolic risk factors in
diabetes: A systematic review and meta-analysis of randomized controlled trials.
AB - BACKGROUND & AIMS: To update the European Association for the Study of Diabetes
(EASD) clinical practice guidelines for nutrition therapy, we conducted a
systematic review and meta-analysis of randomized controlled trials to summarize
the evidence for the effect of vegetarian dietary patterns on glycemic control
and other established cardiometabolic risk factors in individuals with diabetes.
METHODS: We searched MEDLINE, EMBASE, and Cochrane databases through February 26,
2018 for randomized controlled trials >=3 weeks assessing the effect of
vegetarian dietary patterns in individuals with diabetes. The primary outcome was
HbA1c. Secondary outcomes included other markers of glycemic control, blood
lipids, body weight/adiposity, and blood pressure. Two independent reviewers
extracted data and assessed risk of bias. Data were pooled by the generic inverse
variance method and expressed as mean differences (MD) with 95% CIs.
Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).
The overall certainty of the evidence was assessed using the Grading of
Recommendations Assessment, Development, and Evaluation (GRADE) approach.
RESULTS: Nine trials (n = 664 participants) met the eligibility criteria.
Vegetarian dietary patterns significantly lowered HbA1c (MD = -0.29% [95% CI:
0.45, -0.12%]), fasting glucose (MD = -0.56 mmol/L [95% CI: -0.99, -0.13
mmol/L]), LDL-C (MD = -0.12 mmol/L [95% CI: -0.20, -0.04 mmol/L]), non-HDL-C (MD
= -0.13 mmol/L [95% CI: -0.26, -0.01 mmol/L]), body weight (MD = -2.15 kg [95%
CI: -2.95, -1.34 kg]), BMI (MD = -0.74 kg/m2 [95% CI: -1.09, -0.39 kg/m2]) and
waist circumference (MD = -2.86 cm [95% CI: -3.76, -1.96 cm]). There was no
significant effect on fasting insulin, HDL-C, triglycerides or blood pressure.
The overall certainty of evidence was moderate but was low for fasting insulin,
triglycerides and waist circumference. CONCLUSION: Vegetarian dietary patterns
improve glycemic control, LDL-C, non-HDL-C, and body weight/adiposity in
individuals with diabetes, supporting their inclusion for diabetes management.
More research is needed to improve our confidence in the estimates.
CLINICALTRIALS. GOV IDENTIFIER: NCT02600377.
PMID- 29960810
TI - Clinical intervention using Bifidobacterium strains in celiac disease children
reveals novel microbial modulators of TNF-alpha and short-chain fatty acids.
AB - BACKGROUND & AIMS: Celiac disease (CD) is an immune-mediated systemic disease,
caused by ingestion of gluten in genetically predisposed individuals. Gut
microbiota dysbiosis might play a significant role in pathogenesis of chronic
enteropathies and its modulation can be used as an intervention strategy in CD as
well. In this study, we aimed to identify correlations between fecal microbiota,
serum tumor necrosis factor alpha (TNF-alpha) and fecal short-chain fatty acids
(SCFAs) in healthy children and children with CD after administration of
probiotic Bifidobacterium breve BR03 and B632. METHODS: A double-blind placebo
controlled study enrolled 40 children with CD (CD) and 16 healthy children (HC).
CD children were randomly allocated into two groups, of which 20 belonged to the
placebo (PL) group and 20 to the Probiotic (PR) group. The PR group received a
probiotic formulation containing a mixture of 2 strains, B. breve BR03 (DSM
16604) and B. breve B632 (DSM 24706) in 1:1 ratio for 3 months. Subsequently, for
statistical analysis, blood and fecal samples from CD children (on enrolment - T0
and after 3 months, at the end of intervention with probiotic/placebo - T1) and
HC children were used. The HC group was sampled only once (T0). RESULTS:
Verrucomicrobia, Parcubacteria and some yet unknown phyla of Bacteria and Archaea
may be involved in the disease, indicated by a strong correlation to TNF-alpha.
Likewise, Proteobacteria strongly correlated with fecal SCFAs concentration. The
effect of probiotic administration has disclosed a negative correlation between
Verrucomicrobia, some unknown phyla of Bacteria, Synergistetes, Euryarchaeota and
some SCFAs, turning them into an important target in microbiome restoration
process. Synergistetes and Euryarchaeota may have a role in the anti-inflammatory
process in healthy human gut. CONCLUSIONS: Our results highlight new phyla, which
may have an important relation to disease-related parameters, CD itself and
health.
PMID- 29960811
TI - [Beyond mycosis and warts on feet...].
PMID- 29960812
TI - An evaluation of the differences in DNA damage in lymphocytes and repair
efficiencies in patients with schizophrenia and schizoaffective disorder.
AB - Schizophrenia and schizoaffective disorder are chronic and debilitating
psychiatric disorders. The present study was designed to determine DNA damage in
patients with schizophrenia and schizoaffective disorder to assess the roles of
oxidative metabolism and DNA repair mechanisms in this process, to assess the
contribution of drugs, and thus to demonstrate the differences between
schizophrenia and schizoaffective disorder. Thirty schizophrenia and 30
schizoaffective disorder patients, each having at least five years of disease
history, aged between 18 and 60 years with no physical or neurological diseases,
and 30 healthy volunteers participated in the study. Psychometric scales were
applied, and 5 ml of blood was taken from all participants. The DNA damage was
measured in lymphocytes by the comet assay method; the total oxidative parameters
by ELISA; OGG1 and NEIL1 gene expressions by real-time PCR; and the role of drugs
by in vitro assays. The most important finding in this study was that patients
with schizophrenia had significantly greater DNA damage than schizoaffective
disorder patients and the controls. This study also provides evidence of high
oxidative stress statuses and inadequate DNA repair capacities in patients with
schizophrenia. Moreover, psychotropic drugs did not induce any DNA damage to the
lymphocytes according to in vitro analyses. The use of clozapine and adequate
repair processes of the patients were the decisive factors in the prevention of
DNA damage. The results of this study provide a reexamination of schizoaffective
disorder within the schizophrenia spectrum and indicate that schizoaffective
disorder may be considered a different diagnostic category.
PMID- 29960813
TI - Well-being and quality of life among oral cancer patients - Psychological
vulnerability and coping responses upon entering initial treatment.
AB - BACKGROUND: Little is known about the psychological constitution and potential
coping mechanisms of oral cancer patients when they enter initial treatment. This
study aimed at 1) establishing a feasible study protocol and 2) implementing it
to examine patients' coping and psychological responses during the initial
treatment phase in the hospital. METHODS: In three consecutive feasibility phases
a study procedure including measurement time points and instrumentation as well
as a patient recruitment strategy was developed. To assess patients' responses,
the following qualitative (interviews) and quantitative (questionnaires) measures
were applied: WOC-CA, briefCOPE, HADS, EORTCQlQC30- H&N35 and SAM/POMS. RESULTS:
Results revealed a highly burdened and distressed patient group that had not yet
developed clear coping strategies. Further, one third of examined patients showed
severe levels of anxiety and depression, indicating a high vulnerability to
develop psychological disorders. CONCLUSION: At this early stage of oral cancer
treatment, potential psychosocial interventions should prioritize addressing
anxiety and depression to enable patients to develop functional coping strategies
later on.
PMID- 29960814
TI - Clinical evaluation of non-syndromic scaphocephaly surgically corrected with the
procedure of total vertex craniectomy.
AB - The present investigation constitutes a retrospective evaluation of the outcome
in children who received surgical correction of a scaphocephalic phenotype by
median total vertex craniectomy. Between September 2009 and September 2015, a
total of 35 infants with non-syndromic scaphocephaly were treated according to
the same standardized operative technique of total vertex craniectomy by a single
surgeon approach. At the time of surgery, the patients were between 3 and 12
months of age, with a median of 5 months. The mean duration of the procedure was
94 min. The duration of postoperative follow-up was a mean of 24 months (range 6
49 months). A total of 34 (97%) patients were successfully treated by total
vertex craniectomy and were thus classified as category I according to the
Whitaker score. Only one individual was assigned to category IV, necessitating
secondary major craniofacial corrective surgery. Aesthetic outcomes were
excellent in 34 cases and poor in one case. No major complication occurred. The
reoperation rate was 3%. The surgical method we present herein is a wide median
craniectomy which can be applied in young individuals with non-syndromic single
suture scaphocephaly.
PMID- 29960815
TI - Optimized 3D virtually planned intermediate splints for bimaxillary orthognathic
surgery: A clinical validation study in 20 patients.
AB - Orthognathic surgery is indicated for the treatment of significant skeletal
malocclusions and facial dysmorphosis. Recent technological developments allow
surgeons to virtually plan the orthognathic jaw movements. When producing
intermediate splints, overlap between the upper and lower dentitions can occur.
Autorotation of the mandible is often used as a solution for this problem. The
purpose of this study was to present an optimized approach to fabricate digital
intermediate splints based on the use of a scanned thick wax bite to overcome
dental overlap during planning. Twenty patients (9 males and 11 females)
undergoing bimaxillary orthognathic surgery participated in this prospective
study. Planning of the maxillary movements was conducted by the same surgeon. The
thick wax bite was scanned using an intraoral scanner and a special CBCT
protocol. The fabrication of the intermediate splints was done by means of
conventional model surgery and virtual 3D planning-printing. The splints were
clinically assessed by comparing the digitally printed intermediate splints to
the corresponding conventional set-up which served as the clinical standard.
Moreover, reproducibility and comparison tests between the scanned wax bites were
implemented. The root mean square (RMS) for the reproducibility and comparison
tests was respectively 0,15 mm (SD 0,24 mm) and 0,19 mm (SD 0,08 mm). 19 out of
the 20 intermediate digitally 3D printed splints were clinically accepted. This
proposed protocol can be considered as an optimization to the current 3D planning
protocols of bimaxillary orthognathic surgery.
PMID- 29960816
TI - Seed Evolution, A 'Simpler' Story.
AB - Seed evolution is often presented as the evolution of morphological complexity.
Following the steps of Wilhelm Hofmeister, I argue that changes in the
development of one tissue, the megasporangium/nucellus, can explain the origin of
the seed habit. Here, I lay down a 'simpler' story that correlates seed evolution
to nucellus cell fate.
PMID- 29960817
TI - Corrigendum to "Highly sensitive microfluidic paper-based photoelectrochemical
sensing platform based on reversible photo-oxidation products and morphology
preferable multi-plate ZnO nanoflowers" [Biosens. Bioelectron. 110 (2018) 58-64].
PMID- 29960818
TI - Nusinersen in type 1 SMA infants, children and young adults: Preliminary results
on motor function.
AB - We report preliminary data on the six month use of Nusinersen in 104 type 1
patients of age ranging from three months to 19 years, 9 months. Ten of the 104
were classified as 1.1, 58 as 1.5 and 36 as 1.9. Three patients had one SMN2
copy, 65 had two and 24 had three copies. In 12 the SMN2 copy number was not
available. After six months an improvement of more than two points was found in
58 of the 104 (55.7%) on the CHOP INTEND and in 21 of the 104 (20.19%) on the
Hammersmith Infant Neurological Examination (HINE). Changes more than two points
were found in 26/71 patients older than two years, and in seven of the 20 older
than 10 years. Changes >= four points were found in 20/71 older than two years,
and in six of the 20 patients older than 10 years. The difference between
baseline and six months on both CHOP INTEND and HINE was significant for the
whole group (p < 0.001) as well as for the subgroups with two (p < 0.001), and
three SMN2 copies (p < 0.001). Our preliminary results suggest that functional
improvement can be observed in type 1 patients outside the range of the inclusion
criteria used in the Endear study.
PMID- 29960819
TI - Evaluating the PD-1 Axis and Immune Effector Cell Infiltration in Oropharyngeal
Squamous Cell Carcinoma.
AB - PURPOSE: Programmed death-1 (PD-1) inhibitors are approved for the treatment of
patients with recurrent and metastatic squamous cell carcinoma of the head and
neck (SCCHN). Ongoing and planned randomized phase 3 trials are testing the
benefit of combining PD-1/programmed death-ligand 1 (PD-L1) inhibitors with
chemoradiation for patients with locoregionally confined SCCHN. Few studies have
investigated relationships among potential predictive pathologic biomarkers such
as PD-L1, PD-L2, and PD-1 in this population and associations between these
markers and clinical characteristics. METHODS AND MATERIALS: We retrospectively
reviewed records and pathology from 81 patients with locoregional oropharynx
SCCHN treated with curative intent. Samples were analyzed for PD-L1, PD-L2, PD-1,
CD8, and CD56 expression using immunohistochemistry. Human papilloma virus (HPV)
status was determined by p16-immunohistochemistry and confirmed by in situ
hybridization or polymerase chain reaction-based HPV typing. Correlations between
HPV status, clinical features, and recurrence status with immune markers in both
tumor and tumor-associated stroma were determined. Hazard ratios were estimated
via Cox proportional hazards model. RESULTS: Tumor PD-L1 expression was inversely
associated with age (P = .01) and the highest levels of expression (>30% of tumor
cells) were observed in HPV-associated tumors. There was a correlation between
tumor and stromal PD-L1 expression (P = < .0001). PD-1 and CD8 expression within
tumor deposits was associated with HPV status (P = 0.003 and P = .008,
respectively) and decreased local recurrence (P = .001 and P < .001,
respectively). In addition to the association between tumor and stromal PD-1 (P <
.0001), PD-1 was also correlated with tumor PD-L1 expression (P < .001). CD56+
natural killer cell infiltrates correlated with PD-L1 expression. CONCLUSIONS: In
patients with untreated oropharyngeal SCCHN, HPV-associated tumors displayed the
highest levels of PD-L1 expression and PD-1+ and CD8+ immune cells. Locally
recurrent tumors had lower levels of PD-L1, PD-1, and CD-8 positivity. Whereas
almost all SCCHN tumors had CD56+ infiltrating natural killer cells, most tumors
didn't have PD-L2 expression. These associations may help predict which patients
may benefit most from immunotherapeutic approaches.
PMID- 29960820
TI - Imaging gamma-Glutamyltranspeptidase for tumor identification and resection
guidance via enzyme-triggered fluorescent probe.
AB - Development of high selectivity, accurate targeted and noninvasive fluorescent
probe for monitoring specific enzyme activity associated with the tumor is urgent
needed for early diagnosis of cancer and clinical fluorescence interventional
resection guidance treatment. Owing to the invasion of malignant tumor cells,
tumor cells are mixed with normal cells in the actual tumor location, which make
it quite difficult for clinician to diagnose early diagnosis of tumor as well as
resection of tumor. To overcome aforementioned obstacle, herein, an ingenious
enzyme-activated one and two-photon fluorescent probe TCF-GGT was constructed and
synthesized including gamma-GGT enzyme specific identification site and far-red
fluorophore for imaging. Under simulative physiological condition, probe TCF-GGT
demonstrated high selectivity, sensitivity (DL 0.014 mU/mL), rapid response (Te
14 min) for the detection of gamma-GGT enzyme. By virtue of its biocompatibility,
probe was employed for the identification of ovarian cancer cells (A2780 cells)
from normal cells (NIH-3T3 cells), particularly in mixed cultivation dish
(simulate the actual environment of tumor) through 2D&3D fluorescence imaging
with "dual" mark (Nucleic acid labeling used by Hoechst 33342 dye and gamma-GGT
enzyme labeling used by probe TCF-GGT) for the first time. Probe TCF-GGT could be
visualize endogenous gamma-GGT activity in HepG-2 cells and zebrafish on the two
photon confocal platform, which is conduce to estimate the inhibitor of gamma-GGT
enzyme in vivo. Through NaBu (a potential anticancer drug) stimulation, the
changes of gamma-GGT activity were observed in living MCF-7 cells by using this
probe. More importantly, the deep tissue penetration ability of far-red
fluorescence allowed the two-photon fluorescent probe TCF-GGT to real-time track
gamma-GGT activity in tissue slices and tumor xenotransplantation model of mice
by the tail vein injection, which showed that this enzyme-triggered fluorogenic
probe would be a potential tool for preclinical applications of tumor resection.
PMID- 29960821
TI - Early effects of parathyroid hormone on vascularized bone regeneration and
implant osseointegration in aged rats.
AB - The decreased bone mass and impaired osteogenesis capacities that occur with
aging may influence the outcome of dental implants. Parathyroid hormone (PTH) (1
34) is an anabolic agent for the treatment of osteoporosis. However, little is
known about its effects and mechanisms on vascularized bone regeneration and
implant osseointegration in aging. In current study, we adopted both in vivo and
in vitro approaches to explore the mechanisms of early actions of PTH (1-34) on
the angiogenic and osteogenic microenvironment to enhance implant
osseointegration in aged rats. Daily subcutaneous injections of 30 MUg/kg PTH (1
34) were given to female rats aged 20 months beginning on next day of
implantation and lasting for 5 weeks. Radiological and histological analysis
confirmed that PTH (1-34) improved new bone formation, angiogenesis and implant
osseointegration in aged rats in the early stage. The osteogenic potential of
aged bone mesenchymal stem cells (BMSCs) was enhanced, while their adipogenesis
capacity was attenuated. Furthermore, PTH (1-34) was shown to promote
angiogenesis directly via endothelial cell migration and blood vessel formation
in vitro. Meanwhile, PTH (1-34) stimulated more osteoclasts participation in bone
remodeling by secreting angiogenic and osteogenic growth factors to induce early
vascularization and stimulate the migration or differentiation of BMSCs
indirectly. Together, these results demonstrate mechanistic insight into how PTH
(1-34) regulates the angiogenic and osteogenic microenvironment to result in more
active bone remodeling and new bone formation, making it an excellent potential
therapeutic agent for rapid vascularized bone regeneration and implant
osseointegration in the aged population.
PMID- 29960823
TI - Proximal junctional kyphosis following correction surgery in the Lenke 5
adolescent idiopathic scoliosis patient.
AB - BACKGROUND: To investigate the risk factors of proximal junctional kyphosis (PJK)
in Lenke 5 AIS patients after all-pedicle instrumentation and correction, and to
compare the difference of radiographic and clinical outcome between PJK and Non
PJK populations. METHOD: Medical records of Lenke 5 AIS patients were reviewed
from January 2008 to January 2013, included posteroanterior and lateral full
spine X-ray films preoperatively, postoperatively (4-7 days after surgery), and
at final follow-up. Demographic data and radiologic parameters were evaluated.
Based on the proximal junctional angle (PJA) at final follow-up, those patients
were divided into 2 groups: PJK group (n = 35, PJA?10 degrees ), and Non-PJK
group (n = 52, PJA<10 degrees ). Comparisons analyses between PJK and Non-PJK
groups were carried out. Binary logistic Regression analysis was performed to
detect the risk factors of PJK at follow-up. RESULTS: The current study recruited
87 Lenke 5 AIS patients with average follow-up of 4.67 +/- 1.17 years.
Significant differences between PJK and Non-PJK groups were observed as follows:
UIV(P = 0.010), the disruption of junctional ligaments (P < 0.001); preoperative
variables [MTC (P = 0.001), TK(P < 0.001), LL (P = 0.017), SVA (P = 0.036), and
PJA (P = 0.014)], postoperative variables [TLK(P = 0.004), and PJA (P < 0.001)],
and follow-up [SVA (P = 0.014), C-SVA (P < 0.001), and PJA (P0.001). Binary
logistic regression showed that the disruption of junctional ligaments,
postoperative PJA and UIV (upper instrumented vertebra) at proximal or lower
thoracic levels were the main risk factors of PJK [Odds Ratio (OR) = 5.114,
2.345, and 6.212, respectively]. However, the SRS-22 scores did not change
significantly in PJK and Non-PJK groups. CONCLUSION: Greater postoperative PJA,
disruption of junctional ligaments, UIV at lower thoracic levels were the main
risk factors for PJK in Lenke 5 AIS patients. Recommedation: Preserve junctional
ligaments in those individuals with UIV located in the lower thoracic region.
PMID- 29960822
TI - Settable polymer/ceramic composite bone grafts stabilize weight-bearing tibial
plateau slot defects and integrate with host bone in an ovine model.
AB - Bone fractures at weight-bearing sites are challenging to treat due to the
difficulty in maintaining articular congruency. An ideal biomaterial for fracture
repair near articulating joints sets rapidly after implantation, stabilizes the
fracture with minimal rigid implants, stimulates new bone formation, and remodels
at a rate that maintains osseous integrity. Consequently, the design of
biomaterials that mechanically stabilize fractures while remodeling to form new
bone is an unmet challenge in bone tissue engineering. In this study, we
investigated remodeling of resorbable bone cements in a stringent model of
mechanically loaded tibial plateau defects in sheep. Nanocrystalline
hydroxyapatite-poly(ester urethane) (nHA-PEUR) hybrid polymers were augmented
with either ceramic granules (85% beta-tricalcium phosphate/15% hydroxyapatite,
CG) or a blend of CG and bioactive glass (BG) particles to form a settable bone
cement. The initial compressive strength and fatigue properties of the cements
were comparable to those of non-resorbable poly(methyl methacrylate) bone cement.
In animals that tolerated the initial few weeks of early weight-bearing, CG/nHA
PEUR cements mechanically stabilized the tibial plateau defects and remodeled to
form new bone at 16 weeks. In contrast, cements incorporating BG particles
resorbed with fibrous tissue filling the defect. Furthermore, CG/nHA-PEUR cements
remodeled significantly faster at the full weight-bearing tibial plateau site
compared to the mechanically protected femoral condyle site in the same animal.
These findings are the first to report a settable bone cement that remodels to
form new bone while providing mechanical stability in a stringent large animal
model of weight-bearing bone defects near an articulating joint.
PMID- 29960824
TI - Female reproductive factors and risk of all-cause and cause-specific mortality
among women: The Japan Public Health Center-based Prospective Study (JPHC study).
AB - PURPOSE: We investigated the association between reproductive history and
mortality from all and major causes among Japanese women. METHODS: A large-scale
population-based cohort study in Japan included 40,149 eligible women aged 40-69
years in 1990-1994. A total of 4788 deaths were reported during follow-up
(average 20.9 years). A Cox proportional hazards regression model was used to
estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for all
cause and major causes of mortality, adjusting for potential confounders.
RESULTS: Inverse associations with all-cause mortality were found in parous women
(0.74 [0.67-0.82]), women with two or three births compared with a single birth
(2 births: 0.88 [0.78-0.99]; 3 births: 0.83 [0.74-0.94]), parous women who
breastfed (0.81 [0.75-0.87]), women who were older at menopause (0.88 [0.80
0.97]; p-trend: <0.01), and women who had a longer fertility span (0.85 [0.76
0.95]; p-trend: <0.01). A positive association was seen between all-cause
mortality and later age at first birth (>=30 years) than early childbearing (<=22
years). CONCLUSIONS: Our study suggests that parous, two or three births,
breastfeeding, late age at menopause, and longer reproductive span are associated
with lower risk of all-cause of mortality.
PMID- 29960825
TI - The path forward for lignocellulose biorefineries: Bottlenecks, solutions, and
perspective on commercialization.
AB - Lignocellulose biorefinery encompasses process engineering and biotechnology
tools for the processing of lignocellulosic biomass for the manufacturing of bio
based products (such as biofuels, bio-chemicals, biomaterials). While,
lignocellulose biorefinery offers clear value proposition, success at industrial
level has not been vibrant for the commercial production of renewable chemicals
and fuels. This is because of high capital and operating expenditures,
irregularities in biomass supply chain, technical process immaturity, and scale
up challenges. As a result, commercial production of biochemicals and biofuels
with right economics is still lagging behind. To hit the market place, efforts
are underway by bulk and specialty chemicals producing companies like DSM
(Succinic acid, Cellulosic ethanol), Dow-DuPont (1,3-Propanediol, 1,4
Butanediol), Clariant-Global bioenergies-INEOS (bio-isobutene), Braskem
(Ethylene, polypropylene), Raizen, Gran-bio and POET-DSM (Cellulosic ethanol),
Amyris (Farnesene), and several other potential players. This paper entails the
concept of lignocellulose biorefinery, technical challenges for industrialization
of renewable fuels and bulk chemicals and future directions.
PMID- 29960826
TI - Corrigendum to 'Evidence-Based Thresholds for the Volume and Length of Stay
Relationship in Total Hip Arthroplasty: Outcomes and Economies of Scale' [Journal
of Arthroplasty 33 (2018) 2031-2037].
PMID- 29960827
TI - Effects of symmetry, texture, and monocular viewing on geographical slant
estimation.
AB - Hills often appear to be steeper than they are. The unusual magnitude of this
error has prompted extensive experimentation. The judgment mode, such as verbal
vs. action-based measures, the state of the observer - whether exhausted or well
rested - all can influence perceived geographical slant. We hold that slant
perception is inherently shaky as soon as the slope in question is no longer
palpable, that is if it is outside our personal space. To make this point, we
have added symmetry, texture, and depression to the list of factors that might
modulate slant perception. When the frontal slope of a hill is to be judged, it
appears steeper when the side slopes are steep. We have used model hills close to
the subject. Their slopes were judged most accurately when binocular stereoscopic
vision was permitted. When closing one eye, observers grossly overestimated all
slopes. This error was larger for verbal judgments than for judgments made by
indicating the slope with their forearm, however, the pattern of the
overestimation remained unchanged. Surface texture mattered surprisingly little.
Depressed subjects produced exactly the same results as healthy controls. We
conclude that in action space and in vista space (outside immediate personal
space), slopes are overestimated because the visual system attempts to turn the
2D retinal stimulus into a regular 3D object, akin to the erection tendency
(Aufrichtungstendenz) found in diminished or 2D-stimuli. This tendency is
inherently instable and can be swayed by a large number of variables.
PMID- 29960828
TI - Health Systems in Latin America: The Search for Universal Health Coverage.
AB - This paper discusses the health challenges faced by countries in Latin America.
These challenges have two dimensions: those related to the health needs of
populations and those related to the way in which health systems are responding
to these needs. The main conclusion is that in order to improve health conditions
and move towards universal health coverage, Latin American countries need to
design a new generation of policy innovations based on the separation of the
three main functions of health systems: financing, delivery and stewardship.
PMID- 29960829
TI - Executive summary of clinical practice guideline for the management of invasive
diseases caused by Aspergillus: 2018 Update by the GEMICOMED-SEIMC/REIPI.
AB - Aspergillus infection is a significant cause of morbi-mortality in an at-risk
population. The Study Group of Fungal Infections (GEMICOMED) from the Spanish
Society of Infectious Diseases and Clinical Microbiology (SEIMC) has reviewed
announcements made in invasive aspergillosis management. We have organized our
recommendations in such a way as to provide a guide in resolving different
clinical situations concerning the entire spectrum of invasive diseases caused by
Aspergillus in various populations. Diagnostic approach, treatment and
preventions strategies are outlined. It is not our aim that these guidelines
supplant clinical judgment with respect to specific patients; however, it is our
objective to perform a comprehensive summary of quality of care evidence for
invasive aspergillosis management in different settings.
PMID- 29960830
TI - Results reporting in single case experiments and single case meta-analysis.
AB - Single Case Experimental Design is a discipline grounded in applied behavior
analysis where the needs of individual clients and the application of scientific
inquiry are fundamental tenets. These two principles remain tantamount in the
conduct of research using this methodology and the expansion of the method into
evidence-based practice determinations. Although recommendations for quality
indicators are widespread, implementation is not. Concurrent to the rise of
quality indicators is an increasing interest in analysis methodology. Visual
analysis has a history of application and validity, newer forms of analysis less
so. While some argue for concordance between the two, it may be the differences
that are worth exploration in understanding characteristics of trend and
variability in much of the published literature. Design choice and visual
analysis decisions are rarely fully articulated. Statistical analyses are
likewise inadequately justified or described. Recommendations for the explicit
language of reporting as derived from prior meta-analysis and a current review of
two leading journals provides a scaffold consistent with existing guidelines but
additive in detail, exemplars, and justification. This is intended to improve
reporting of results for individual studies and their potential use in future
meta-analytic work.
PMID- 29960831
TI - Prognostic Value of Testing PD-L1 Expression After Radical Cystectomy in High
risk Patients.
AB - INTRODUCTION: The use of cisplatin-based adjuvant chemotherapy (AC) after radical
cystectomy (RC) is a highly controversial issue and has been infrequently used
owing to the high rates of postoperative complications, cisplatin ineligibility,
and lack of randomized trials. Checkpoint inhibitors such as nivolumab,
pembrolizumab, or atezolizumab are currently being tested in phase III studies in
the adjuvant setting owing to their more favorable safety profile compared with
chemotherapy. The aim of the present study was to investigate whether
compartmentalization of programmed cell death ligand 1 (PD-L1) expression in
different locations of RC specimens influences recurrence-free survival (RFS)
after RC. MATERIALS AND METHODS: PD-L1 expression was quantified on tumor cells
and immune cells by immunohistochemistry in 83 "high-risk" patients (stage >=
pT3a and/or pN+ disease) who had undergone RC without cisplatin-based AC.
RESULTS: PD-L1 (>= 1%) was expressed on tumor cells in 33 patients (39.8%) and
immune cells in 51 patients (61.4%), respectively. PD-L1 positivity on tumor
cells was not associated with RFS (P = .455). In contrast, PD-L1+ expression on
immune cells was significantly associated with shorter RFS compared with PD-L1-
expression (P = .015). CONCLUSIONS: We have confirmed the high heterogeneity of
PD-L1 cell type-dependent expression, with the resulting divergent outcomes.
Ultimately, no clear statement about PD-L1 expression as a prognostic biomarker
for further AC after RC could be made, although PD-L1 expression on immune cells
seemed to have the greatest effect in predicting the outcome.
PMID- 29960832
TI - What the internist should know about stem cell transplant in the elderly patient.
AB - Most hematological malignancies are increasing in frequency with age. Allogeneic
hematopoietic cell transplantation (allo-HCT) is a potentially curative
therapeutic option for patients with malignant and non-malignant hematological
diseases. The treatment of elderly patients with advanced hematological
malignancies has expanded to include reduced intensity conditioning allo-HCT.
Physicians increasingly refer older patients for allo-HCT due to more experience
and improved supportive care in allo-HCT. This review article discusses the
available data regarding the feasibility, tolerability, toxicity, and
effectiveness of allo-HCT in different hematological diseases in the elderly.
Over the past decade, utilization and survival after allo-HCT have increased in
patients >=70 years. Selected adults >=70 years with hematological diseases
should be evaluated for transplantation.
PMID- 29960833
TI - Royal jelly supplementation reduces skeletal muscle lipotoxicity and insulin
resistance in aged obese rats.
AB - BACKGROUND: Consumption of a high-fat diet (HFD) in aged rats is associated with
several metabolic disorders. The mechanism of skeletal muscle lipotoxicity and
insulin resistance (IR) is multi-factorial, but the exact mechanism of how aging
affects these processes unknown. Royal jelly (RJ) is a dietary supplement with
many physiological and pharmacological properties. No previous studies have
demonstrated the protective effects and mechanism of RJ in aged obese rats.
OBJECTIVES: The study was carried to investigate the effects of aging and HFD on
skeletal muscles, and adipose tissue metabolism and inflammation, in aged rats,
and whether RJ could combat such adverse effects. METHODOLOGY: A total of 40 male
rats were divided into5 groups; young rats fed a standard diet, aged rats fed a
standard diet, aged rats fed RJ, aged rats fed a HFD, and aged rats fed both a
HFD and RJ for 8 weeks. We investigated changes in body weights (BW), abdominal
fat weights, total cholesterol, triglycerides (TG), low density lipoprotein
cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c), muscle TG, and
IR levels. Also, concentrations of TNF-alpha receptor 1(TNFR1) were estimated in
the serum and adipose tissues. RESULTS: Aged, obese rats showed increased BW,
adipose weights, IR, and disturbed serum and muscle lipids. Also, TNFR1 was
increased. Rats fed RJ showed decreased adiposity, improved lipids' profiles,
improved IR, and decreased TNFR1. CONCLUSION: Aging and HFD were associated with
disturbed metabolism, and muscle lipotoxicity and inflammation, while RJ could
counteract muscle lipotoxicity in rats and reduce IR, most likely due to an anti
inflammatory effect.
PMID- 29960835
TI - Temporal Changes in Characteristics, Treatment and Outcomes of Heart Failure
Patients Undergoing Percutaneous Coronary Intervention Findings from Melbourne
Interventional Group Registry.
AB - BACKGROUND: Limited data exist on whether outcomes of patients with heart failure
(HF) undergoing percutaneous coronary intervention (PCI) have improved over time.
The purpose of this study was to assess temporal trends in patient
characteristics, treatment and outcomes of patients with HF undergoing PCI.
METHODS: Using data from the Melbourne Interventional Group (MIG), we evaluated
temporal trends of procedure volume, major adverse cardiac events (MACE; a
composite of all-cause mortality, myocardial infarction and target vessel
revascularisation) and rates of cardiovascular readmission, all-cause death and
cardiovascular death in consecutive patients with HF undergoing PCI. Change over
time was assessed by Box-Jenkins autoregressive integrated moving average (ARIMA)
models. RESULTS: Data from 1604 patients were analysed. In our cohort, there were
no significant changes in the number of procedures performed annually and patient
characteristics between January 2005 and December 2014. Optimal use of HF therapy
has improved over the study period. Planned clopidogrel therapy of more than 12
months increased in tandem with increasing use of drug-eluting stents (DES).
Procedural success was high (>=90%). However, the rates of MACE, cardiovascular
readmission, all-cause death and cardiovascular death remained unchanged
throughout the study period. CONCLUSIONS: Clinical outcomes in HF patients
undergoing PCI have remained unchanged despite improvement in medical technology
and contemporary therapeutic measures.
PMID- 29960834
TI - TRIF deficiency protects non-obese diabetic mice from type 1 diabetes by
modulating the gut microbiota and dendritic cells.
AB - The incidence of type 1 diabetes (T1D) is determined by both genetic and
environmental factors. In recent years, the gut microbiota have been identified
to be an important environmental factor that could modify diabetes
susceptibility. We have previously shown that Myeloid differentiation primary
response gene 88 (MyD88), a major adaptor protein downstream of most innate
immune Toll-like receptor (TLR) signaling, is important for mediating diabetes
susceptibility in the non-obese diabetic (NOD) mouse model of human T1D. Here we
report the role of TIR-domain-containing adapter-inducing interferon-beta (TRIF)
in T1D development, as TRIF is an important adaptor protein downstream of TLR3
and TLR4 signaling. We found that TRIF-deficient (TRIF-/-) NOD mice were
protected from development of diabetes, but only when housed with TRIF-deficient
(TRIF-/-) NOD mice. When housed with TRIF-sufficient wild type (WT, i.e.,
TRIF+/+) NOD mice, the mice developed diabetes. We further investigated the gut
microbiota as a potential cause for the altered diabetes development.
Interestingly, TRIF-/-NOD mice had a different microbiota composition compared to
WT NOD mice, only if they were housed with TRIF-/-NOD mice. However, the
composition of gut microbiota in the TRIF-/-NOD mice was indistinguishable from
WT NOD mice, if they were housed with WT NOD mice. The difference in the gut
microbiota in TRIF-/-NOD mice, due to cohousing, accorded with the diabetes
development in TRIF-/-NOD mice. Comparing the gut microbiota in TRIF-/- and WT
NOD mice, we identified changes in percentage of Sutterella, Rikenella and
Turicibacter species. Moreover, bacteria from WT NOD mice induced significantly
stronger inflammatory immune responses in vitro compared to those from TRIF-/-NOD
mice. Further immunological analysis revealed impaired function of dendritic
cells and reduced T cell activation and proliferation in TRIF-/-NOD mice. Our
data show that TRIF-deficiency protects NOD mice from diabetes development
through alteration of the gut microbiota and reduced immune cell activation;
however, that protection is over-ridden upon exposure to WT NOD bacteria.
Therefore exposure to different microbiota can modify disease susceptibility
determined by genetic factors related to innate immunity.
PMID- 29960836
TI - Clinical Implications of Contrast-Induced Nephropathy in Patients Without
Baseline Renal Dysfunction Undergoing Coronary Angiography.
AB - BACKGROUND: The clinical implications of different definitions of contrast
induced nephropathy (CIN) in patients without baseline renal dysfunction are not
well defined. METHODS: Consecutive patients at a single centre without baseline
renal dysfunction (estimated glomerular filtration rate, eGFR>=60ml/min/1.73m2)
undergoing coronary angiography or percutaneous coronary intervention (PCI), were
systematically evaluated for long-term risk of mortality following CIN using two
broad definitions: an absolute increase from baseline in serum creatinine (SCr)
>=0.3mg/dl (mild to severe absolute CIN) and a relative increase from baseline of
25% (mild to severe relative CIN) within 72hours. RESULT: Of 2823 subjects alive
before discharge following coronary angiography there were 320 episodes of mild
to severe relative CIN (11.3%) and 125 of mild to severe absolute CIN (4.4%).
During a median follow-up of 2.3years, 73 patients (3.2%) died. After adjustment
for confounders, mild to severe absolute CIN was associated with an adjusted
hazard ratio (HR) (95% confidence interval) for all-cause mortality of 3.31 (1.74
6.30) (p<0.0001) and relative CIN with an adjusted HR of 1.92 (1.09, 3.38)
(p=0.024). The risk of mortality rose with severity of CIN. Two commonly used
definitions of CIN combining absolute and relative terms (increase >= 0.3mg/dl or
50%, and >= 0.5mg/dl or 25% from the baseline) confirmed these results.
CONCLUSION: Among patients without baseline renal dysfunction undergoing coronary
angiography, the incidence of CIN can range widely depending on definition.
Absolute CIN is less common than relative CIN. Regardless of definition, CIN is
associated with a markedly increased risk of long-term mortality. This finding
requires confirmation in multicentre studies.
PMID- 29960837
TI - Heart failure with preserved ejection fraction: A systemic disease linked to
multiple comorbidities, targeting new therapeutic options.
AB - Heart failure is a pathology associated with severe morbidity and mortality. In
this large field, heart failure with preserved ejection fraction (HFpEF) appears
to be an increasing global health problem; it should be considered as a
progressive syndrome, characterized by complex mechanisms of systemic and cardiac
adaptation that vary over time, particularly with ageing. Multiple biological
phenotypes contribute to the heterogeneous clinical syndrome. HFpEF emerges as a
model with proinflammatory cardiovascular and non-cardiovascular coexisting
comorbidities, leading to systemic inflammation and subsequent fibrosis and to
diverse clinical HFpEF phenotypes. All of these aspects are often present in the
elderly population, bordering on the emergence of a true geriatric syndrome. The
therapeutic approach cannot be uniform, and must involve management of the
different comorbidities according to a phenotype treatment strategy, respecting
the pharmacological approaches to the biological pathways involved in the
proinflammatory comorbidity-related status. Future studies should consider these
multiple distinct HFpEF phenotypes in the development of large morbimortality
trials adapted to comorbidities or specific risk factors.
PMID- 29960838
TI - Costochondral grafting for paediatric temporomandibular joint reconstruction: 10
year outcomes in 55 cases.
AB - Costochondral grafting (CCG) can be used for the reconstruction of ankylotic,
hypoplastic, and resected temporomandibular joint (TMJ) defects. CCGs have
previously been considered the gold standard in children due to their growth
potential and autogenous origin, but the disadvantages are unpredictable growth
and joint ankylosis. This was a retrospective study of all children who received
CCGs for TMJ reconstruction from 1985 to 2004, to allow a 10-year follow-up.
Fifty-five patients were included in this study, with 74 grafts being placed;
their mean age was 7.9+/-4.2years. Infection-related ankylosis (18.2%) and
craniofacial microsomia (16.4%) were the most common diagnoses. Overall, 58.2% of
patients suffered one or more complications over the follow-up period, with
ankylosis (32.7%) and overgrowth (16.4%) being most common. There was a
significant correlation between those with infection-related ankylosis and
subsequent complications (chi2=8.8, df=1, P<0.005), while ankylotic patients in
general exhibited greater overall complication rates (chi2=9.0, df=1, P<0.005).
Patients with congenital TMJ defects were more likely to be complication-free
than those with acquired defects (chi2=4.0, df=1, P<0.05). Caution is advised
when placing CCGs in paediatric patients with ankylosed TMJs, especially those
with infection-related ankylosis.
PMID- 29960839
TI - Excess mortality for people diagnosed with type 2 diabetes in 2012 - Estimates
based on claims data from 70 million Germans.
AB - BACKGROUND AND AIMS: The hazard ratio (HR) is a meaningful concept for comparing
the mortality of people with and without type 2 diabetes (T2D). Nevertheless,
there is only one German study estimating age-specific HRs. Thus, this study
aimed to provide population-wide age-specific HRs for Germany using a novel
method based on aggregated population data. METHODS AND RESULTS: We used an
illness-death model and published data on T2D prevalence and incidence as well as
mortality in the German general population to estimate age-specific HRs in the
year 2012 for the population aged 65-90 years. For men, the overall HR was 2.3,
which decreased from 2.8 between 65 and 69 years old to 1.6 between 85 and 90
years old. For women, the overall HR was 3.0, which decreased from 4.2 to 1.7 in
the same age groups, respectively. CONCLUSION: In Germany, men and women in 2012
with T2D aged 65-90 years experienced a three-to four-fold higher mortality
compared to people without T2D, which might indicate that the excess mortality
could be higher than in countries with comparable health care systems. Female sex
and younger age were associated with higher excess mortality.
PMID- 29960840
TI - Yield of brain imaging among neurologically normal children with headache on
wakening or headache waking the patient from sleep.
AB - BACKGROUND: Headache on wakening (HoW) or sleep interruption secondary to
headache (SIH) has been commonly regarded as a potential sign of raised
intracranial pressure and therefore a sign of significant underlying pathology
that necessitates further investigation. Current recommendations for neuroimaging
in patients with HoW/SIH are neither consistent nor clear across headache
guidelines published both nationally and internationally. AIM: The main aim of
this study was to ascertain the relevance of HoW and/or SIH as an indication for
routine neuroimaging. METHODS: This study focused on clinically well patients
with normal neurological examinations who had experienced HoW or SIH. Demographic
and neuroradiological data were collected prospectively and the headache
diagnosis was based on the International Classification of Headache Disorders.
RESULTS: 102/1065 patients reported either HoW and/or SIH. There were 57/102
(56%) females, 45/102 males (44%), and 33/102 (32%) of ethnic minority. Their age
ranged between 5 and 17 years. 79/102 (77%) patients with HoW, 19/102 (19%) with
SIH and 4/102 (4%) with both HoW and SIH. Headache diagnosis included migraine (n
= 67; 66%), tension type headaches (n = 16; 16%), medication overuse headaches (n
= 11; 11%), and sinusitis (n = 1; 1%). Neuroimaging was performed in 101/102
patients; imaging was normal for 97 scanned patients, and showed non-significant
abnormality in the remaining 4 patients. CONCLUSION: HoW or SIH among clinically
well and neurologically normal paediatric patients was most likely to be caused
by primary headaches, particularly migraine or tension type headaches. This
symptom alone among healthy and clinically well children is not an indication for
routine neuroimaging and is unlikely to be caused by sinister aetiologies.
PMID- 29960841
TI - Self-reported needs after pediatric stroke.
AB - BACKGROUND: Pediatric stroke has the potential for long term impact on the lives
of children and their families. Child-centred intervention depends on
understanding of needs from diagnosis onwards. However, little is known about the
health and care support self-reported needs of this population. AIMS: This study
aimed to describe the nature and extent of needs (met and unmet) of pediatric
stroke patients and their families and compare these with previously reported
adult stroke needs. METHODS: The questionnaire, adapted from a previously
published adult stroke study, was conducted with parents of children who had an
ischemic or haemorrhagic stroke between birth - 18 years, and young people with
stroke now aged between 12 and 18 years. Participants were recruited from three
tertiary pediatric stroke clinics in England. Levels and type of needs, and self
reported neurological impairment were captured. Comparisons of needs was reported
descriptively and explored using Chi-square test. RESULTS: Of 44 participants (39
parents, 5 young people), over two thirds reported at least one unmet need. Over
half had difficulties in school-related activities, and over one-third in leisure
activities and social relationships. Participants reported similar nature and
extent of need when compared to previously reported adult stroke needs. Higher
severity of neurological impairment was associated with higher number of needs.
CONCLUSIONS: Children and young people and their parents have high levels of
unmet need across a range of health domains in the months and years after
pediatric stroke. This information supports the importance of a needs-based
approach to maximising health and well-being.
PMID- 29960842
TI - Outcome of newly diagnosed high risk medulloblastoma treated with carboplatin,
vincristine, cyclophosphamide and etoposide.
AB - Medulloblastoma is the most common malignant brain tumor among children. Although
molecular study has been included in the new classification, in developing
countries with limited resources the previous Chang staging system is still used.
Therefore, treatment with postoperative radiation and chemotherapy remains the
standard treatment. One common complication after treatment is ototoxicity,
mainly due to radiation and cisplatinum. We report a revised chemotherapy
protocol, replacing cisplatinum with carboplatin in newly diagnosed
medulloblastoma cases. All 23 patients in this study had high risk
medulloblastoma. Mean (SD) age was 9.5 +/- 3.1 years. The 5-year progression free
survival (PFS), 5-year overall survival (OS), and 10-year OS were 41.8 +/- 12.2%,
60.0 +/- 11.2%, and 48.0 +/- 14.0 respectively. Most patients had grade 3-4
hematologic toxicity. Twelve patients had hearing tests, with 11 patients having
grade 0 and 1 patient having grade 1 according to the Brock criteria.
PMID- 29960843
TI - Strategies to Optimize the Efficacy of Anthelmintic Drugs in Ruminants.
AB - Anthelmintic resistance in human and animal pathogenic helminths has been
spreading in prevalence and severity. Multidrug resistance is a widespread
problem in livestock animals. The use of available pharmacology-based information
is critical to the design of successful future approaches for parasite control.
Relevant scientific work supporting the main strategies to optimize anthelmintic
therapy in ruminants under the current drug-resistance scenario is described
here. We emphasize the need for further integrated pharmaco-parasitological
knowledge to extend the lifespan of both traditional and novel anthelmintic
compounds, and to progress in the identification of complementary/alternative
measures of parasite control in livestock animals.
PMID- 29960845
TI - LncRNA TUG1 promoted viability and associated with gemcitabine resistant in
pancreatic ductal adenocarcinoma.
AB - OBJECTIVE: To investigate the underlying mechanism of lncRNA TUG1 in pancreatic
ductal adenocarcinoma (PDAC). METHODS: The expression of TUG1 was defined by qRT
PCR. The apoptotic cells were detected by flow cytometry assay. The cell
migration and invasion were measured by scratch assay and Transwell assay. The
level of ERK pathway was detected using Western blot. RESULTS: Compared with
normal tissues and cells, the expression of TUG1 was up-regulated in pancreatic
cancer tissue and cells. Meanwhile, knockdown of TUG1 could promote PDAC cells
apoptosis and inhibit PDAC cells viability, migration and invasion. In addition,
overexpression of TUG1 enhanced the gemcitabine chemoresistance of PDAC cells.
Surprisingly, gemcitabine combined with SCH772984 (a suppressor of ERK pathway)
could reverse the drug resistance resulted from overexpression of TUG1.
CONCLUSION: TUG1 promoted the viability of PDAC cells and enhanced its resistance
of gemcitabine.
PMID- 29960844
TI - Salidroside protects renal tubular epithelial cells from hypoxia/reoxygenation
injury in vitro.
AB - Oxidative stress, inflammation and cell apoptosis are important mechanisms of
renal ischemia/reperfusion (I/R) injury. Salidroside, a natural phenylpropanoid
glycoside, possesses anti-inflammatory, anti-oxidative, and anti-apoptotic
effects. However, the effect of salidroside on renal I/R injury has not been
fully elucidated. The present study aimed to investigate the effect of
salidroside on renal I/R injury in vitro. Our results showed that salidroside
improved the viability of human renal tubular epithelial cells (HK-2) in response
to hypoxia/reoxygenation (H/R). Salidroside caused apparent decrease in the
levels of reactive oxygen species (ROS) and malondiaidehyde (MDA), and
significant increase in superoxide dismutase (SOD) activity in HK-2 cells.
Pretreatment with salidroside markedly inhibited the production levels of tumor
necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in a
dose-dependent manner. Salidroside treatment exhibited significant increase in
Bcl-2 expressions, and decrease in Bax expressions and caspase-3 activity when
compared with the H/R group. Salidroside decreased the levels of toll-like
receptor 4 (TLR4) and p-p65 in HK-2 cells. Overexpression of TLR4 significantly
attenuated the effects of salidroside on cell viability, oxidative stress,
cytokine production and cell apoptosis in HK-2 cells. These findings indicated
that salidroside protected HK-2 cells from H/R stimulation, which was mediated by
the TLR4/NF-kappaB pathway.
PMID- 29960847
TI - Optimising surveillance for relapse of Wilms' tumour.
PMID- 29960846
TI - Bisphenol A induces Nrf2-dependent drug-metabolizing enzymes through
nitrosylation of Keap1.
AB - Bisphenol A (BPA) is an endocrine-disrupting chemical, and activates the aryl
hydrocarbon receptor (AhR) and the estrogen receptor, leading to the induction of
drug metabolizing enzymes. In this study, we found that BPA increased nitric
oxide (NO) levels but not reactive oxygen species (ROS) levels in the human
hepatoma cell line, Hep3B, and induced drug-metabolizing enzymes such as UDP
glucuronosyltransferase (UGT). Nuclear factor erythroid 2-related factor 2 (Nrf2)
has been reported to be activated by ROS through inactivation of its regulating
protein, Kelch-like ECH-associated protein (Keap1), and to be the key mediator of
phase I and phase II drug metabolizing enzymes, and phase III drug transporters.
Treatment of Hep3B with BPA increased the levels of nitrous oxide, a metabolite
of nitric oxide and activated Nrf2 by nitrosylation of Keap1, leading to the
induction of heme oxygenase-1 (HO-1) and UGT2B1 mRNAs. A nitric oxide donor, 1
Hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC7), also
activated Nrf2 and a NOS inhibitor, NG-Monomethyl-l-arginine, monoacetate salt (L
NMMA), inhibited activation of Nrf2 by BPA. Furthermore, calcium efflux by BPA
was observed. These results suggested the new idea that BPA increases NO levels
and activates Nrf2 via Keap1 inactivation, leading to induction of Nrf2-dependent
drug-metabolizing enzymes.
PMID- 29960849
TI - Left ventricular noncompaction cardiomyopathy: Recent update on genetics,
usefulness of biomarker, and speckle imaging.
PMID- 29960848
TI - Relapse of Wilms' tumour and detection methods: a retrospective analysis of the
2001 Renal Tumour Study Group-International Society of Paediatric Oncology Wilms'
tumour protocol database.
AB - BACKGROUND: Wilms' tumour is the most common renal cancer in childhood and about
15% of patients will relapse. There is scarce evidence about optimal surveillance
schedules and methods for detection of tumour relapse after therapy. METHODS: The
Renal Tumour Study Group-International Society of Paediatric Oncology (RTSG-SIOP)
Wilms' tumour 2001 trial and study is an international, multicentre, prospective
registration, biological study with an embedded randomised clinical trial for
children with renal tumours aged between 6 months and 18 years. The study covers
243 different centres in 27 countries grouped into five consortia. The current
protocol of SIOP surveillance for Wilms' tumour recommends that abdominal
ultrasound and chest x-ray should be done every 3 months for the first 2 years
after treatment and be repeated every 4-6 months in the third and fourth year and
annually in the fifth year. In this retrospective cohort study of the protocol
database, we analysed data from participating institutions on timing, anatomical
site, and mode of detection of all first relapses of Wilms' tumour. The primary
outcomes were how relapse of Wilms' tumour was detected (ie, at or between
scheduled surveillance and with or without clinical symptoms, scan modality, and
physical examination) and to estimate the number of scans needed to capture one
subclinical relapse. The RTSG-SIOP study is registered with Eudra-CT, number 2007
004591-39. FINDINGS: Between June 26, 2001, and May 8, 2015, of 4271 eligible
patients in the 2001 RTSG-SIOP Wilms' tumour database, 538 (13%) relapsed. Median
follow-up from surgery was 62 months (IQR 32-93). The method used to detect
relapse was registered for 410 (76%) of 538 relapses. Planned surveillance
imaging captured 289 (70%) of these 410 relapses. The primary imaging modality
used to detect relapse was reported for 251 patients, among which relapse was
identified by abdominal ultrasound (80 [32%] patients), chest x-ray (78 [31%]),
CT scan of the chest (64 [25%]) or abdomen (20 [8%]), and abdominal MRI (nine
[4%]). 279 (68%) of 410 relapses were not detectable by physical examination and
261 (64%) patients did not have clinical symptoms at relapse. The estimated
number of scans needed to detect one subclinical relapse during the first 2 years
after nephrectomy was 112 (95% CI 106-119) and, for 2-5 years after nephrectomy,
500 (416-588). INTERPRETATION: Planned surveillance imaging captured more than
two-thirds of predominantly asymptomatic relapses of Wilms' tumours, with most
detected by abdominal ultrasound, chest x-ray, or chest CT scan. Beyond 2 years
post-nephrectomy, a substantial number of surveillance scans are needed to
capture one relapse, which places a burden on families and health-care systems.
FUNDING: Great Ormond Street Hospital Children's Charity, the European Expert
Paediatric Oncology Reference Network for Diagnostics and Treatment, The Danish
Childhood Cancer Foundation, Cancer Research UK, the UK National Cancer Research
Network and Children's Cancer and Leukaemia Group, Societe Francaise des Cancers
de l'Enfant and Association Leon Berard Enfant Cancereux and Enfant et Sante,
Gesellschaft fur Padiatrische Onkologie und Hamatologie and Deutsche Krebshilfe,
Grupo Cooperativo Brasileiro para o Tratamento do Tumor de Wilms and Sociedade
Brasileira de Oncologia Pediatrica, the Spanish Society of Pediatric Haematology
and Oncology and the Spanish Association Against Cancer, and SIOP-Netherlands.
PMID- 29960850
TI - Recent advances in the metamaterial-inspired biosensors.
AB - Metamaterials (MM)-inspired microwave biosensors are a valuable addition to the
field of diagnostic approaches and prognostic tools. The fundamental principle
behind these biosensors is unique dielectric signatures corresponding to
healthy/diseased tissues. Relying on nonionizing radiation and offering an
increased resolution with accuracy comparable to that of ultrasound devices, they
are an attractive solution for noninvasive and label-free biosensing
applications. High-quality-factor MM-inspired resonators are integrated with
microfluidics to accelerate the lab-on-chip and point-of-care diagnostic
approaches owing to the small detection volume and overall compact size of these
devices. A variety of biomolecular detection, glucose detection and hyperthermia
treatment using state-of-the-art MM-inspired biosensors have been discussed.
Optical transduction techniques (e.g., surface plasmon resonance) which enhance
the sensitivity in terms of limit-of-detection and resolution, have also been
outlined. Utilization of microwave biosensors as therapeutic agents is at its
initial stages owing to lack of required sensitivity and reliability in recently
proposed MM-inspired biosensors.
PMID- 29960851
TI - Effectiveness of robo-assisted lower limb rehabilitation for spastic patients: A
systematic review.
AB - BACKGROUND: Though many rehabilitative treatments are available for treatment of
spasticity, thus the effectiveness of different robo-rehabilitative devices needs
to be evaluated through a systematic review. OBJECTIVE: The objective of this
study is to focuses on the efficacy of Robot assistive rehabilitation device for
the removal of spasticity from the lower limb of Spastic patients. DATA
SOURCESSOURCES: PubMed, Web of Sciences, EMBASE (Excerpta Medical database), CDSR
(Cochrane database of systematic reviews), Scopus, IEEE Xplore, Wiley online
library, MEDLINE (OvidSP), Science Direct, Springer Link were from January 1980
to September 2017 DATA EXTRACTIONEXTRACTION: Seventy-one publications from eleven
databases published were selected using keywords Ankle foot, spasticity, robotic
rehabilitation, efficacy of robotics and Ankle foot rehabilitation. The review is
narrowed down to twenty-six articles which were selected for they focused on
effects of Robot assistive rehabilitation device quantitatively. RESULT: A
quantitative study from analyzing 26 studies comprising of 786 subjects is
carried out. The major outcome of the effectiveness of the robot assistive
therapy for the movement of ankle and functioning of gait is deduced. As the used
protocols and treatment procedures vary, made comparative study complex or
impracticable. CONCLUSION: Robo-rehabilitation possesses an ability to provide
unified therapy protocols with greater ease in comparison to conventional
therapies. They continuously prove to be irreplaceable assistant devices when it
comes to providing excellent treatment in terms of improvement from this study.
Though many mechatronic devices are available but the devices for treatment of
early stage rehabilitation of stroke patients is very limited.
PMID- 29960852
TI - Improving compliance in adults with epilepsy on a modified Atkins diet: A
randomized trial.
AB - PURPOSE: To determine whether use of a ketogenic formula during the first month
of the modified Atkins diet (MAD) in adults with drug-resistant epilepsy (DRE)
improves seizure reduction and compliance compared to MAD alone. METHODS: Eighty
adults (age >=18 years) with DRE and >=4 reliably quantifiable seizures/month
were enrolled. All participants were trained to follow a 20 g/day net
carbohydrate limit MAD. Patients were randomized to receive one 8-ounce (237 mL)
tetrapak of KetoCal(r), a 4:1 ketogenic ratio formula, daily in combination with
MAD during the first month (treatment arm) or second month (control/cross-over
arm). Patients recorded urine ketones, weight, and seizure frequency and followed
up at 1 and 2 months. RESULTS: By 1 month, 84% of patients achieved ketosis
(median of 4-4.5 days). At 1 month, the treatment arm had a significantly higher
ketogenic ratio and more patients with a >=1:1 ketogenic ratio compared to the
control arm. There was no difference in median seizure frequency, proportion of
responders (>=50% seizure reduction), or median seizure reduction from baseline
between groups. However, patients treated with KetoCal(r) during the first month
were significantly more likely to continue MAD for 6 months or more. CONCLUSION:
Although supplementing MAD with a ketogenic formula in the first month did not
increase the likelihood of reducing seizures compared to MAD alone, significantly
more adults remained on MAD long-term with this approach. This suggests a
potential strategy for encouraging compliance with MAD in adults with DRE.
PMID- 29960853
TI - The Strengths and Limitations of Claims Based Research in Countries With Fee for
Service Reimbursement.
PMID- 29960854
TI - Causes of Death Among Avalanche Fatalities in Colorado: A 21-Year Review.
AB - INTRODUCTION: A better understanding of the nature of morbidity and mortality in
avalanche accidents helps direct both rescue efforts as well as preventive
strategies to reduce fatalities. METHODS: We reviewed all avalanche fatalities
from the avalanche years beginning in 1994 to 2015 in the state of Colorado,
United States, using the database maintained by the Colorado Avalanche
Information Center. For each fatality, we obtained the coroner's official
determination of cause of death, and autopsy records if one was performed. We
used these records to determine cause of death. Injury severity scores (0-75
scale) were calculated for those victims who underwent autopsy. RESULTS:
Mortality information was available for 110 fatalities occurring during the 21
year study period. Of these, 64 underwent autopsy. Asphyxia was the cause of
death in 65% of fatalities (72/110). Trauma was the cause of death in 29% of the
fatalities (32/110). Of these, the primary cause was multiple system trauma in
38% (12/32), head trauma in 31% (10/32), and spinal injuries in 19% (6/32). Of
the victims who died of asphyxia and had autopsy, only 10% (4/42) also had
significant trauma, defined as an injury severity score greater than 15. There
were 6 fatalities from other causes, including hypothermia, drowning, and primary
cardiac arrest. There was no correlation between trauma and mode of travel,
avalanche type, or starting zone elevation. CONCLUSIONS: Asphyxia was the primary
cause of death in avalanche fatalities in Colorado during our study period. The
incidence of fatal trauma was 29% and did not correlate with user group
demographics or avalanche characteristics.
PMID- 29960856
TI - The ATP-stimulated translocation promoter (ASTP) activity of glycerol kinase
plays central role in adipogenesis.
AB - Glycerol kinase (GK) is a multifunctional enzyme located at the interface of
carbohydrate and fat metabolism. It contributes to both central carbon metabolism
and adipogenesis; specifically, through its role as the ATP-stimulated
translocation promoter (ASTP). GK overexpression leads to increased ASTP activity
and increased fat storage in H4IIE cells. We performed metabolic flux analysis in
human GK-overexpressing H4IIE cells and found that overexpressing cells had
significantly altered fluxes through central carbon and lipid metabolism
including increased flux through the pentose phosphate pathway and increased
production of lipids. We also observed an equal contribution of glycerol to
carbohydrate metabolism in all cell lines, suggesting that GK's alternate
functions rather than its enzymatic function are important for these processes.
To further elucidate the contributions of the enzymatic (phosphorylation) and
alternative (ASTP) functions of GK in adipogenesis, we performed experiments on
mammalian GK and E. coli GK. We determined that the ASTP function of GK (which is
absent in E. coli GK) plays a greater role than the enzymatic activity in these
processes. These studies further emphasize GK's diverse functionality and
provides fundamental insights into the multiple protein functions of glycerol
kinase.
PMID- 29960857
TI - Is there a place for surgical treatment of nonpharmacoresistant epilepsy?
AB - Epilepsy surgery has been shown to be the best possible treatment in well-defined
and difficult-to-treat epilepsy syndromes, such as mesial temporal lobe epilepsy
with unilateral hippocampal sclerosis, even early in the course of the disease if
pharmacoresistance is proven. This review addresses the question if epilepsy
surgery may be justified today even in nonpharmacoresistant cases. There are two
possible groups of patients: first, there are epilepsy syndromes with a benign
spontaneous course or with a potentially good treatment prognosis under
appropriate antiepileptic drug (AED) treatment. Second, there are epilepsies with
potentially worse AED treatment prognosis in which appropriate AED treatment has
not yet been applied because of the short course of the disease, tolerability
problems that prevented usually effective dosing, or adherence issues. In group
one, the good spontaneous prognosis or the usually satisfying course under AED
treatment in line with the commonly generalized underlying epileptogenesis does
not suggest that epilepsy surgery is a realistic alternative, not even in cases
with distinct focal clinical and/or electroencephalography (EEG) patterns like in
Rolandic epilepsy with centrotemporal spikes. In the second group, the recent
International League Against Epilepsy (ILAE) definition should allow assessment
of individual pharmacoresistance early after the onset of the disease in order to
avoid any delay. Concerns about a potential disease-specific or drug-specific
cognitive decline that could be avoided in early surgery are speculative, a
matter of controversial discussion, and certainly not relevant, if
pharmacoresistance is consequently addressed in time according to the ILAE
recommendations. One should also not forget that even in typically
pharmacoresistant epilepsy syndromes that are suitable for surgical procedures,
satisfying courses do exist that would not require early or any epilepsy surgery.
Therefore, in almost any instance, epilepsy surgery as initial treatment or
immediately after a first AED is still not recommended although, especially in
cases with nonadherence to AEDs, it may be occasionally considered in order to
outweigh the risks of ongoing seizures and epilepsy if surgery is not performed.
PMID- 29960859
TI - Investigation of the interaction between bta-miR-222 and the estrogen receptor
alpha gene in the bovine ovarium.
AB - The aim of the present study was to investigate the posttranscriptional
regulation of bta-miR-222 and the estrogen receptor (ER)-alpha gene in cows. The
preovulatory follicles (POFs) were detected and ER-alpha levels in the corpus
luteum (CL) were measured via immunofluorescent method. Afterwards, an ELISA test
was performed to detect estradiol- and progesterone-active follicles, and the
expression levels of ER-alpha, progesterone receptor (PR), and bta-miR-222 were
measured via qRT-PCR. Finally, a western blot analysis was performed to determine
ER-alpha protein levels. Immunofluorescence staining was highly positive in the
follicular phase, showing ER-alpha and PR immunopositivity. In the luteal phase,
ER-alpha immunopositivity decreased in lutein cells, whereas the PRs were
observed to be similar in intensity to those in follicular phase. While the
estradiol levels were higher in the POFs, the progesterone level was higher in
the CL. In the CL, the transcription levels of ER-alpha and PR mRNA were observed
to be the same as in the POFs; however, the expression of bta-miR-222 was lower.
In the CL, the transcription level of ER-alpha mRNA was lower than that of PR
mRNA, and the expression level of bta-miR-222 was higher than that of PR mRNA.
The results of the western blot analysis show that the ER-alpha protein level in
the CL was lower than that in the POFs. Taken together, our results here suggest
that there is a negative correlation between bta-miR-222 and ER-alpha expression
during follicular development in cow ovaries.
PMID- 29960858
TI - Differential expression of interferon-gamma, IL-4 and IL-10 in peripheral blood
mononuclear cells during early pregnancy of the bovine.
AB - Maternal systemic immune response is regulated by conceptus-derived signals
through peripheral blood mononuclear cells (PBMCs) via blood circulation during
early pregnancy in cattle. In this study, the PBMCs from day 18 in non-pregnant
cows and days 14, 18 and 30 in pregnant cows were used to explore the expression
of interferon-gamma (IFN-gamma), interleukin 4 (IL-4) and IL-10, and the plasma
progesterone (P4) concentration was also determined. The results showed that the
expression levels of mRNA and the protein of IFN-gamma were lower and that IL-4
and IL-10 were higher in the PBMCs from the pregnant cows than in those of non
pregnant cows. From this study, early pregnancy induced a lower Th1 immunity (IFN
gamma) and a higher Th2 immunity (IL-4 and IL-10) in the PBMCs, which may be
related to interferon-tau and P4, thereby contributing to successful pregnancy in
cattle.
PMID- 29960860
TI - When change is the only constant: The promise of longitudinal neuroimaging in
understanding social anxiety disorder.
AB - Longitudinal studies offer a unique window into developmental change. Yet, most
of what we know about the pathophysiology of psychiatric disorders is based on
cross-sectional work. Here, we highlight the importance of adopting a
longitudinal approach in order to make progress towards identifying the
neurobiological mechanisms of social anxiety disorder (SAD). Using examples, we
illustrate how longitudinal data can uniquely inform SAD etiology and timing of
interventions. The brain's inherently adaptive quality requires that we model
risk correlates of disorders as dynamic in their expression. Developmental
theories regarding timing of environmental events, cascading effects and
(mal)adaptations of the developing brain will be crucial components of
comprehensive, integrative models of SAD. We close by discussing analytical
considerations when working with longitudinal, developmental data.
PMID- 29960861
TI - Function of three RuBisCO enzymes under different CO2 conditions in
Hydrogenovibrio marinus.
AB - The obligate chemolithoautotrophic bacterium, Hydrogenovibrio marinus MH-110 has
three ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) isoenzymes,
designated CbbLS-1, CbbLS-2, and CbbM, which are encoded by the cbbL1S1, cbbL2S2,
and cbbM genes, respectively. Functions of these isoenzymes at different CO2
concentrations were investigated using deletion mutants of their genes. Deletion
of cbbL1 had no effect on cell growth under any of the test growth conditions.
The cbbL2 mutant was unable to grow under lower (<=0.15%) CO2 conditions, though
it grew normally under higher (>=2%) CO2 conditions. Growth of the cbbM mutant
was retarded under higher CO2 conditions but was not affected by lower CO2
conditions. These results indicate that CbbLS-2 and CbbM specifically function
under lower and higher CO2 conditions, respectively. The growth retardation of
the cbbL2 and cbbM mutants was not restored by complementation with plasmids
carrying the cbbL2S2 and cbbM genes, respectively. The cbbL2S2 and cbbM genes are
followed by the carboxysome genes and the cbbQmOm genes, respectively. Co
expression of these downstream genes was probably necessary for the in vivo
function of CbbLS-2 and CbbM. CbbLS-1 was upregulated in the cbbL2 and cbbM
mutants under the lower and higher CO2 conditions, respectively, indicating that
the expression of cbbL1S1 was controlled to compensate the deficiency of the
other RuBisCO isoenzymes.
PMID- 29960862
TI - Urinary neutrophil gelatinase-associated lipocalin in type 2 diabetes: Relation
to nephropathy and retinopathy.
AB - BACKGROUND: Diabetes mellitus is the leading cause of end stage renal disease
worldwide. Early identification of diabetic nephropathy even before appearance of
microalbuminuria is a challenge for early prevention of occurrence and
progression of this complication. Neutrophil gelatinase-associated lipocalin is a
small protein that belongs to the lipocalin protein. Urinary neutrophil
gelatinase-associated lipocalin is a promising early marker in different renal
problems. AIM OF THE WORK: To measure urinary neutrophil gelatinase-associated
lipocalin in type 2 diabetic patients and to assess its role as an early marker
for diagnosis of diabetic nephropathy and diabetic retinopathy. PATIENT AND
METHODS: The current study included 60 subjects with type 2 diabetes and 20
healthy control subjects. Diabetic subjects were divided into 3 groups according
to urinary albumin creatinine ratio; 20 normoalbuminuric patients, 20 micro
albuminuric patients and 20 macroalbuminuric patients. They were subjected to
history taking, full clinical examination, fundus examination, anthropometric
measurement, urinary neutrophil gelatinase-associated lipocalin and urinary
albumin creatinine ratio. RESULTS: Urinary neutrophil gelatinase-associated
lipocalin was higher in all diabetic groups than in the control group, with no
difference in between diabetic groups. The difference was of great value when
comparing normoalbuminuric group with control as albumin creatinine ratio was not
different while the urinary neutrophil gelatinase-associated lipocalin was
statistically significant (5.94 +/- 1.85 ng/dl vs 1.96 +/- 0.65, p < 0.001). No
correlation was found with retinopathy. CONCLUSION: Urinary neutrophil gelatinase
associated lipocalin is a sensitive marker for early detection of diabetic
nephropathy even in normoalbuminuric patients denoting early tubular damage
before microalbuminuria. It is not correlated with retinopathy.
PMID- 29960863
TI - Management of asenapine treatment in clinical practice: Recommendations from a
panel of experts.
AB - INTRODUCTION: The choice of an antipsychotic should be based on bipolar disorder
(BD) symptoms and the particular needs of each patient, as well as the adverse
events potentially associated with treatment. Asenapine is an atypical
antipsychotic indicated for the management of type-I BD, with distinct
pharmacokinetic and receptor affinity profiles. MATERIAL AND METHODS:
Recommendations document developed by a panel of experts with extensive
experience in the use of asenapine in psychiatric care, including emergency
department, hospital, and outpatient care. Recommendations were discussed in a
single meeting and were based on both the clinical experience of the panel of
experts and the empirical evidence provided in the scientific literature.
RESULTS: The present document describes the patient profile that best suits the
pharmacodynamic characteristics of asenapine, as well as the advantages and
limitations of the pharmacokinetics associated with the sublingual route. The
document also addresses the main safety issues of asenapine and suggests
interventions aimed at mitigating the most frequent adverse reactions associated
with asenapine treatment. Finally, the article provides advice on dosing and
overall management of asenapine treatment, including the combination with other
treatments and the switch from other antipsychotics to asenapine. CONCLUSIONS: In
this recommendations document, we provide clinicians with guidance on the use of
asenapine in real-life practice, including the identification of patients who
best suit the characteristics of this antipsychotic.
PMID- 29960855
TI - Degree of implementation of preventive strategies for post-ICU syndrome: Multi
centre, observational study in Spain.
AB - AIM: To evaluate the degree of implementation of protocols associated with the
prevention of intensive-care-unit (ICU) acquired muscle weakness, and the
presence of the physiotherapist in various ICU in Spain. METHOD: A descriptive,
cross-sectional study performed in 86 adult ICU in Spain between March and June
2017. Neurosurgical and major burns ICU were excluded. A multiple-choice survey
was used that included questions on protocols for glycaemia control, sedation,
pain assessment, delirium prevention, delirium management and early mobilisation.
The survey was completed using a user-protected application and password. The
Student's t-test or Mann-Whitney U test and Pearson's correlation or Spearman's
Rho test were used for the inferential analysis. RESULTS: Eighty-nine point five
percent of the ICU had a glycaemia control protocol, with a predominating range
of 110-140mg/dl. Seventy-four point four percent evaluated sedation levels,
although only 36% had sedation protocols. Pain assessment was carried out on
communicative patients in 73.7%, and on uncommunicative patients in only 47.5%.
Only 37.2% performed daily screening to detect delirium and 31.4% of the ICU had
delirium prevention protocols, 26.7% had delirium management protocols and 14%
had protocols for early mobilisation. Thirty-four point nine percent requested
cross consultation with the rehabilitation department. CONCLUSIONS: The
implementation of the different protocols associated with the prevention of ICU
acquired muscle weakness was high in relation to glycaemia control protocols,
sedation level and pain assessment in communicative patients, and was low for
early mobilisation and delirium screening and prevention. Similarly, the
physiotherapist was seldom present in the ICU.
PMID- 29960864
TI - Cumulative dose of bevacizumab associates with albuminuria rather than
podocyturia in cancer patients.
AB - Angiogenesis inhibition with bevacizumab, a monoclonal antibody against vascular
endothelial growth factor A (VEGF-A), is an anticancer treatment associated with
hypertension and renal glomerular toxicity referred to as a preeclampsia-like
syndrome. In preeclampsia, podocyturia predates proteinuria and clinical features
of preeclampsia, and is regarded as a biomarker of ongoing glomerular injury.
Using a quantitative polymerase chain reaction of the podocyte-specific molecules
nephrin, podocin, and VEGF-A in the urine, we examined whether podocyturia is
present in bevacizumab-treated cancer patients, and whether it relates to
proteinuria and the cumulative dose of bevacizumab. Urine samples were cross
sectionally collected from 43 bevacizumab-treated patients, 21 chemotherapy
treated patients, and 7 healthy controls. Urinary protein-to-creatinine ratio
(mean and range) was 32.0 mg/mmol (5.2-284.4) in the bevacizumab group, compared
with 11.4 mg/mmol (1.1-21.0) in the chemotherapy group and 7.4 mg/mmol (3.9-16.5)
(P < .05) in healthy controls, whereas urinary albumin-to-creatinine ratio values
in the three groups were, respectively, 18.9 mg/mmol (0.1-227.7), 1.5 mg/mmol
(0.2-3.5), and 0.2 mg/mmol (0.1-0.4) (P < .05). The cumulative dose of
bevacizumab ranged from 550 to 93,628 mg. Urinary podocin mRNA expression was
undetectable in 59% of participants, urinary nephrin mRNA expression per mmol
creatinine ranged from 0.0 to 5.3 and urinary VEGF-A mRNA expression from 0.0 to
2.7. Urinary nephrin mRNA expression did not correlate to the albumin-to
creatinine ratio or the cumulative dose of bevacizumab, whereas the latter
correlated with the albumin-to-creatinine ratio (r = 0.77; P < .001). Our results
demonstrate that the cumulative dose of bevacizumab is closely correlated with
albuminuria but not with podocyturia as measured with the quantitative polymerase
chain reaction technique, challenging the feasibility of this measurement to
monitor ongoing glomerular injury in patients chronically treated with
bevacizumab.
PMID- 29960866
TI - Prevalence and predictors of postoperative thiamine deficiency after vertical
sleeve gastrectomy.
PMID- 29960865
TI - The role of kidney in the inter-organ coordination of endogenous glucose
production during fasting.
AB - OBJECTIVE: The respective contributions to endogenous glucose production (EGP) of
the liver, kidney and intestine vary during fasting. We previously reported that
the deficiency in either hepatic or intestinal gluconeogenesis modulates the
repartition of EGP via glucagon secretion (humoral factor) and gut-brain-liver
axis (neural factor), respectively. Considering renal gluconeogenesis reportedly
accounted for approximately 50% of EGP during fasting, we examined whether a
reduction in renal gluconeogenesis could promote alterations in the repartition
of EGP in this situation. METHODS: We studied mice whose glucose-6-phosphatase
(G6Pase) catalytic subunit (G6PC) is specifically knocked down in the kidneys (K
G6pc-/- mice) during fasting. We also examined the additional effects of
intestinal G6pc deletion, renal denervation and vitamin D administration on the
altered glucose metabolism in K-G6pc-/- mice. RESULTS: Compared with WT mice, K
G6pc-/- mice exhibited (1) lower glycemia, (2) enhanced intestinal but not
hepatic G6Pase activity, (3) enhanced hepatic glucokinase (GK encoded by Gck)
activity, (4) increased hepatic glucose-6-phosphate and (5) hepatic glycogen
spared from exhaustion during fasting. Increased hepatic Gck expression in the
post-absorptive state could be dependent on the enhancement of insulin signal
(AKT phosphorylation) in K-G6pc-/- mice. In contrast, the increase in hepatic GK
activity was not observed in mice with both kidney- and intestine-knockout (KI
G6pc-/- mice). Hepatic Gck gene expression and hepatic AKT phosphorylation were
reduced in KI-G6pc-/- mice. Renal denervation by capsaicin did not induce any
effect on glucose metabolism in K-G6pc-/- mice. Plasma level of 1,25 (OH)2 D3, an
active form of vitamin D, was decreased in K-G6pc-/- mice. Interestingly, the
administration of 1,25 (OH)2 D3 prevented the enhancement of intestinal
gluconeogenesis and hepatic GK activity and blocked the accumulation of hepatic
glycogen otherwise observed in K-G6pc-/- mice during fasting. CONCLUSIONS: A
diminution in renal gluconeogenesis that is accompanied by a decrease in blood
vitamin D promotes a novel repartition of EGP among glucose producing organs
during fasting, featured by increased intestinal gluconeogenesis that leads to
sparing glycogen stores in the liver. Our data suggest a possible involvement of
a crosstalk between the kidneys and intestine (via the vitamin D system) and the
intestine and liver (via a neural gut-brain axis), which might take place in the
situations of deficient renal glucose production, such as chronic kidney disease.
PMID- 29960867
TI - miR-320 mediates diabetes amelioration after duodenal-jejunal bypass via
targeting adipoR1.
AB - BACKGROUND: Duodenal-jejunal bypass (DJB) surgery can improve type 2 diabetes
(T2D) dramatically. Accumulating evidence implicates deficiency of hepatic
adiponectin signaling as a contributor to gluconeogenesis disorders, and some
microRNAs (miRNAs) regulate adiponectin receptors (AdipoR1, AdipoR2). We
investigated the effects of DJB on hepatic gluconeogenesis, lipid metabolism, and
inflammation as well as the effects of miRNA-320 (AdipoR1-targeting miRNA) on DJB
induced T2D amelioration. OBJECTIVES: To investigate the essential role of miRNAs
in regulation of adiponectin signaling by targeting AdipoR1 in DJB and the
underlying mechanisms. SETTING: University Hospital, China. METHODS: We studied
hepatic adiponectin signaling changes and hepatic miRNAs involved in a rat model
of DJB. We investigated the effects of miR-320 on AdipoR1 signaling in buffalo
rat liver cell lines. Liver tissues and glucose tolerance tests were analyzed in
DJB rats injected with lentivirus encoding a miR-320 mimic. RESULTS: Transfection
with a miR-320 mimic reduced AdipoR1 protein levels and inhibited downstream
adiponectin signaling; transfection with a miR-320 inhibitor elicited the
opposite effects. A luciferase assay confirmed that miR-320 binds to the 3'
untranslated regions of AdipoR1. Global upregulation of miR-320 expression in DJB
rats showed impaired gluconeogenesis, lipid metabolism, and relatively higher
expression of inflammation markers. CONCLUSION: miR-320 regulates the adipoR1
mediated amelioration of T2D in DJB and should be explored as a potential target
for T2D treatment.
PMID- 29960868
TI - MiR-122 marks the differences between subcutaneous and visceral adipose tissues
and associates with the outcome of bariatric surgery.
AB - The physiological roles and clinical impacts of the differences between visceral
fat (VF) and subcutaneous fat (SF) are unclear. The present study aimed to
compare the miRNA signatures between visceral fat (VF) and subcutaneous fat (SF)
and study their influences on outcomes of bariatric surgery. To study the
microRNA signatures of the VF and SF in obesity, we performed paired microRNA
arrays of the adipose tissues from 20 bariatric surgery patients. The microRNA
analysis identified miR-122 as the most significant signature between VF and SF.
The tissue distribution, functions, and influences on adipogensis of miR-122 were
analysed by Northern blotting, microRNA mimics and inhibitors, and whole-genome
microarray analysis. The outcomes of body weight changes after bariatric surgery
were analysed and correlated with the miR-122 abundances. Northern blotting
confirmed that miR-122 was highly expressed in VF and SF. Bioinformatics analysis
of the microarray revealed that proliferator activator receptor-gamma (PPAR
gamma) signalling was critically affected by miR-122. The modulation of PPAR
gamma by miR-122 was confirmed in murine adipocytes and human adipose tissues.
Furthermore, the differentiation of preadipocytes was significantly influenced by
miR-122. In obese patients receiving bariatric surgery, the ratio of VF and SF
miR-122 abundance correlated with 6-month and 1-year % excess body weight loss.
Our findings indicate that miR-122 is highly expressed in adipose tissue. The
abundance of miR-122 affects PPAR-gamma signalling and adipocytes differentiation
in vitro and human adipose tissues. Higher miR-122 in VF may be associated with
greater body weight loss after bariatric surgery.
PMID- 29960869
TI - Predictors of postpartum weight retention among urban Malaysian mothers: A
prospective cohort study.
AB - BACKGROUND: Women of childbearing age are predisposed to becoming overweight or
obese. This study determines the mean, prevalence and factors associated with 6
months postpartum weight retention among urban Malaysian mothers. METHODS: A
prospective cohort study was conducted at baseline (after delivery), 2, 4 and 6
months postpartum. From 638 eligible mothers initially recruited, 420 completed
until 6 months. Dependent variable was weight retention, defined as difference
between weight at 6 months postpartum and pre-pregnancy weight, and weight
retention >=5kg was considered excessive. Independent variables included socio
demographic, history of pregnancy and delivery, lifestyle, practices and
traditional postpartum practices. RESULTS: Average age was 29.61+/-4.71years,
majority (83.3%) were Malays, 58.8% (low education), 70.0% (employed), 65.2%
(middle income family), 33.8% (primiparous) and 66.7% (normal/instrumental
delivery). Average gestational weight gain was 12.90+/-5.18kg. Mean postpartum
weight retention was 3.12+/-4.76kg, 33.8% retaining >=5kg. Bivariable analysis
showed low income, primiparity, gestational weight gain >=12kg, less active
physically, higher energy, protein, carbohydrate and fat intake in diet, never
using hot stone compression and not continuing breastfeeding were significantly
associated with higher 6 months postpartum weight retention. From multivariable
linear regression analysis, less active physically, higher energy intake in diet,
gestational weight gain >=12kg, not continuing breastfeeding 6 months postpartum
and never using hot stone compression could explain 55.1% variation in 6 months
postpartum weight retention. CONCLUSION: Women need to control gestational weight
gain, remain physically active, reduce energy intake, breastfeed for at least 6
months and use hot stone compression to prevent high postpartum weight retention.
PMID- 29960870
TI - Antifungal activity of Camellia sinensis crude extracts against four species of
Candida and Microsporum persicolor.
AB - OBJECTIVE OF THE STUDY: Candidiasis and dermatophytoses are benign infections in
humans and animals, but they are very dreaded diseases in immunocompromised
individuals. These infections become resistant to different treatments which make
them more dangerous. In this work, we tried to find a new way for treating them.
So we were interested in the antifungal activity of Camellia sinensis (tea); this
plant is known to have many health benefits. MATERIALS AND METHODS: We tested the
ability of the acetone and aqueous crude extracts of the plant to inhibit in
vitro the growth of Candida albicans, Candida glabrata, Candida tropicalis,
Candida krusei and Microsporum persicolor. Then, the antifungal activity against
these species was tested in vivo in mice. RESULTS: The results showed that the
acetone crude extract had the most important in vitro activity against all the
fungi. But in vivo it was only the most active against Candida albicans, Candida
glabrata, Candida tropicalis and Microsporum persicolor. Candida krusei was more
sensitive to the aqueous crude extract. CONCLUSION: These results indicated that
tea could be considered to treat infections caused by the five tested species.
PMID- 29960871
TI - Spotted fever group Rickettsiae in Ticks from Missouri.
AB - Tick-borne rickettsioses pose a major health threat among vector-borne infections
in Missouri but there are some uncertainties regarding the vector competence and
range of tick species, as well as the virulence of certain bacterial species. A
survey was developed and implemented to assess local healthcare practitioners'
awareness of the prevalence and diagnosis of tick-borne diseases. In addition,
ticks collected from rural areas of St. Louis County, Missouri, were evaluated to
detect spotted fever group (SFG) rickettsiae and to determine the most common
tick species present. Physician responses showed a good general awareness of tick
borne diseases and antibiotic choices but responses varied regarding length of
treatment, the most common tick-borne diseases, and tick vectors. No new tick
vectors were collected in the area; Rickettsia amblyommatis was the predominant
SFG species, and it was detected in Amblyomma americanum, Dermacentor variabilis,
andIxodes scapularis; Rickettsia montanensis was detected in D. variabilis. The
high prevalence of Rickettsia amblyommatis in these ticks suggests that there is
a high risk of exposure to this SFG rickettsial species to humans and that it may
be providing some cross-protective immunity to R. rickettsii.
PMID- 29960872
TI - Development of a serodiagnostic IgM-ELISA for tick-borne encephalitis virus using
subviral particles with strep-tag.
AB - Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe
encephalitis in humans. IgM antibody detection is useful for the serological
diagnosis of TBEV infection, because IgM has high specificity for each flavivirus
and indicates a recent infection. Commercial IgM-ELISA kits are somewhat
expensive and difficulties in their sensitivity have been suggested due to their
format and formalin-inactivated antigens. Therefore, the development of an
inexpensive IgM-ELISA with high specificity and sensitivity is needed. In this
study, a MU-capture ELISA was developed to detect TBEV-specific IgM antibodies
using subviral particles (SPs) with strep-tag (strep-SP-IgM-ELISA). The results
of our strep-SP-IgM-ELISA were highly correlated with diagnoses made by the
neutralization test (sensitivity: 94.1%), and our strep-SP-IgM-ELISA could detect
anti-TBEV IgM antibodies in patients who could not be diagnosed with the
neutralization test. Besides, 51 of 52 positive samples by a commercial IgM-ELISA
were also diagnosed as positive by our strep-SP-IgM-ELISA (98.1%), and our strep
SP-IgM-ELISA could detect anti-TBEV IgM antibodies in all samples that were
inconclusive based on the commercial IgM-ELISA. Our strep-SP-IgM-ELISA will be
useful for diagnoses in TBE-endemic areas.
PMID- 29960873
TI - The Use of Stromal Vascular Fraction in the Treatment of Male Sexual Dysfunction:
A Review of Preclinical and Clinical Studies.
AB - INTRODUCTION: Stem cell therapy using stromal vascular fraction (SVF) is a
promising treatment modality. SVF is comprised of a mixture of adipose-derived
stem cells, endothelial precursor cells, and immune modulatory cells that act
synergistically to facilitate angiogenesis and epithelial cell differentiation.
This makes SVF an attractive option for men's sexual disorders that require
reconstitution of vasculature and endothelial lining, namely erectile dysfunction
(ED) and Peyronie's disease (PD). AIM: The objective of this study was to compare
and contrast the available literature regarding the use of SVF in the treatment
of male sexual dysfunction. METHODS: A literature review was performed in PubMed
with the keywords "stromal vascular fraction" and/or "erectile dysfunction"
and/or "Peyronie's disease" and/or "sexual dysfunction." MAIN OUTCOME MEASURES:
The main outcome measure for preclinical studies was erectile function, as
measured by changes in intracavernous pressures, and results of histopathologic
analysis of corporal tissue. Clinical endpoint analysis in humans included
various patient questionnaires. RESULTS: For ED, there were 5 preclinical studies
included in the analysis, with 1 Phase 1 clinical trial in humans. Major
limitations of both the preclinical and clinical studies included the absence of
SVF component analysis, and short duration of follow-up. Despite a paucity of
preclinical studies, there was a single clinical study assessing the efficacy of
combination SVF and shock wave therapy in the treatment of PD. Limitations of
this study included an absence of a control group and the use of subjective data.
CONCLUSION: Preclinical and clinical data in the use of SVF for the treatment of
male sexual dysfunction is deficient. Even though multiple medicinal disciplines
are studying the use of SVF on a myriad of pathologies, further investigative
work elucidating the mechanism and potential adverse effects of SVF need to be
performed before clinical trials are undertaken. Haney NM, Gabrielson A, Kohn TP,
Hellstrom WJG. The Use of Stromal Vascular Fraction in the Treatment of Male
Sexual Dysfunction: A Review of Preclinical and Clinical Studies. Sex Med Rev
2018;XX:XXX-XXX.
PMID- 29960874
TI - Cardiovascular Safety of Phosphodiesterase Type 5 Inhibitors After Nearly 2
Decades on the Market.
AB - BACKGROUND: The phosphodiesterase-5 (PDE5) inhibitors that have been available
for nearly 20 years are highly effective in treating erectile dysfunction and
have been consistently shown to be safe when used according to package insert
instructions. AIM: To review the cardiovascular (CV) safety of PDE5 inhibitors
used to treat erectile dysfunction. METHODS: PubMed, the Derwent Drug File, and
Embase were searched to identify papers published from 1990-2016 presenting CV
safety data for PDE5 inhibitors. OUTCOMES: This narrative review focuses mainly
on papers published in the last 10 years with CV safety data for sildenafil,
tadalafil, or vardenafil. RESULTS: Similar to earlier studies, newer studies
demonstrate that PDE5 inhibitors do not show an increased incidence of serious CV
adverse events such as cardiac death or myocardial infarction. There are drug
drug interactions with PDE5 inhibitors that for the most part are now commonly
known, and PDE5 inhibitors are generally safe to use with other commonly used
drugs including antihypertensive agents. CONCLUSION: PDE5 inhibitors are a class
of drugs that when used appropriately demonstrate a favorable CV safety profile
and present some encouraging signals for new CV indications, which will require
additional study. Kloner RA, Goldstein I, Kirby MG, et al. Cardiovascular Safety
of Phosphodiesterase Type 5 Inhibitors After Nearly 2 Decades on the Market. Sex
Med Rev 2018;6:583-594.
PMID- 29960875
TI - A specialized method of sputum collection and processing for therapeutic
interventions in cystic fibrosis.
AB - Cystic fibrosis (CF) lung disease is characterized by aggressive neutrophil
dominated inflammation mediated in large part by neutrophil elastase (NE), an
omnivorous protease released by activated or disintegrating neutrophils and a key
therapeutic target. To date, several short-term studies have shown that anti-NE
compounds can inhibit NE and have anti-inflammatory effects. However, progression
to large-scale or multicenter clinical trials has been hampered by the fact that
the current gold standard methodology of evaluating airway NE inhibition,
bronchoalveolar lavage (BAL), is invasive, difficult to standardize across sites
and excludes those with severe lung disease. Attempts to utilize sputum that is
either spontaneously expectorated (SS) or induced (IS) have been hindered by poor
reproducibility, often due to the various processing methods employed. In this
study, we evaluate TEmperature-controlled Two-step Rapid Isolation of Sputum
(TETRIS), a specialized method for the acquisition and processing of SS and IS.
Using TETRIS, we show for the first time that NE activity and cytokine levels are
comparable in BAL, SS and IS samples taken from the same people with CF (PWCF) on
the same day once this protocol is used. We correlate biomarkers in TETRIS
processed IS and clinical outcome measures including FEV1, and show stability and
reproducible inhibition of NE over time in IS processed by TETRIS. The data offer
a tremendous opportunity to evaluate prognosis and therapeutic interventions in
CF and to study the full spectrum of people with PWCF, many of whom have been
excluded from previous studies due to being unfit for BAL or unable to
expectorate sputum.
PMID- 29960876
TI - Randomized controlled study comparing simultaneous modulated accelerated
radiotherapy versus simultaneous integrated boost intensity modulated
radiotherapy in the treatment of locally advanced head and neck cancer.
AB - OBJECTIVES: Comparison of two fractionation schedules of intensity modulated
radiotherapy (IMRT) for locally advanced head and neck cancer - simultaneous
integrated boost (SIB-IMRT) and simultaneous modulated accelerated radiotherapy
(SMART) boost in terms of toxicity and survival end-point measures. PATIENTS AND
METHODS: Sixty patients with locally advanced head and neck cancer were
randomized in two treatment arms (SIB-IMRT [control arm] and SMART boost arm
[study arm]). In the control arm, patients received 70, 63 and 56 Gy in 35
fractions to clinical target volumes (CTV) 1, 2 and 3, respectively. In the study
arm, patients received 60 and 50 Gy to CTV 1 and CTV 3, respectively. Toxicities,
progression free survival (PFS) and overall survival (OS) were compared between
both arms. RESULTS: Baseline patient-related characteristics were comparable
between the arms except for primary site of tumour. No significant differences
were noted in acute toxicities between the arms except for fatigue which was
statistically higher for control arm. No significant differences in 2-year late
toxicities were observed. The median follow-up duration was 25.5 (range, 1.8
39.9) months. The 2-year PFS was 53.3% and 80.0% (p = 0.028) for control and
study arm, respectively. The 2-year OS was 60.0% and 86.7% (p = 0.020) in control
and study arms, respectively. Multivariate analysis showed clinical stage and
site to be significant predictors for OS and PFS, respectively. CONCLUSIONS: The
SMART boost technique can be a feasible alternative fractionation schedule that
reduces the overall treatment time, maintaining comparable toxicity and survival
compared with SIB-IMRT.
PMID- 29960877
TI - [Efficacy and safety of replacement treatment in isolated growth hormone
deficiency].
AB - INTRODUCTION: Growth in patients with isolated growth hormone (GH) deficiency is
heterogeneous despite treatment due to the low specificity of diagnostic tests,
making it necessary to define efficacy variables. AIMS: To evaluate efficacy of
hormone replacement therapy in children with isolated GH deficiency. METHODS:
Observational-ambispective study of patients treated in our department in the
last 14 years for isolated GH deficiency. This was defined as a GH level less
than 7.4mg/dl in response to 2 stimulation tests in patients with height<2SD and
a decreased growth rate. RESULTS: The study included a total 97 patients, of whom
69% were boys. The large majority (89.58%) achieved final height. None of them
had side effects. The median dose of GH used was 0.028mg/kg/day (0.03-0.025).
There was a gain of 1.17 SD in final height. Around three-quarters (71.13%) of
the patients were reassessed in adulthood, of whom 39.4% maintained the
deficiency, and 79.31% achieved target range height. Target height, estimated
height, and the total pubertal gain were positively correlated with final height,
while the bone age/chronological age ratio and the initial insulin-like growth
factor-1 showed a negative correlation. CONCLUSIONS: A majority of patients
reached target size, although only a few of them maintained the deficiency in
adulthood. Target size, estimated adult height, and pubertal variables are
directly related to adult height, while bone age/chronological age and insulin
like growth factor-1 were inversely related, and these can be used as efficacy
variables. No adverse effects were observed in the sample with the doses used for
the treatment.
PMID- 29960878
TI - A modified stakeholder participation assessment framework for design thinking in
health innovation.
AB - Increasing pressure to improve health outcomes of populations with limited
resources has prompted an emphasis on innovation. Design thinking has been
proposed as a systematic approach to innovation in health, owing to its human
centred methodology that prioritises deep empathy for the end-users' desires,
needs and challenges, which results in a better understanding of the problem in
order to develop more comprehensive and effective solutions. A key feature of
design thinking is stakeholder participation. If design thinking is going to be
used as an approach to design and implement effective, equitable and sustainable
health solutions, assessing stakeholder participation should be integrated into
the process. Therefore, the purpose of this review is to i) provide an analysis
of the literature on assessing stakeholder participation in health and ii)
propose a framework based on the literature analysis that can be used to assess
stakeholder participation during the design thinking process in health
innovation. Drawing from participatory research in health, where stakeholder
participation is recognised as a core principle that facilitates the
implementation of solutions, we integrate stakeholder evaluation tools into the
design thinking approach. We draw on an assessment framework that describes
levels of stakeholder participation by their involvement in making decisions
about their health. Using a 5-point continuum where the lower end represents the
medical approach (professionals make all the decisions) and the upper end
represents the community development approach (all stakeholders are key decision
makers), we propose a modified assessment framework to evaluate stakeholder
participation during the design thinking process. The modified framework provides
a simple and practical tool to evaluate stakeholder participation. Stakeholders
can rate their perceived level of participation, as well as that of the other
stakeholders. Evaluation of participation in a design thinking project may be
used to improve participation, and therefore the uptake and sustainability of
innovations. The framework may also be used in design thinking beyond health
applications.
PMID- 29960879
TI - La tuberculose durant la grossesse: une menace trop souvent negligee.
PMID- 29960880
TI - The FLORA study: presenting a novel IPF trial design.
PMID- 29960881
TI - Disadvantages of set length antibiotic treatment for pulmonary exacerbation.
PMID- 29960882
TI - Benefits of set length antibiotic treatment for pulmonary exacerbations.
PMID- 29960883
TI - In Vivo Decoding Mechanisms of the Temporal Patterns of Blood Insulin by the
Insulin-AKT Pathway in the Liver.
AB - Cells respond to various extracellular stimuli through a limited number of
signaling pathways. One strategy to process such stimuli is to code the
information into the temporal patterns of molecules. Although we showed that
insulin selectively regulated molecules depending on its temporal patterns using
Fao cells, the in vivo mechanism remains unknown. Here, we show how the insulin
AKT pathway processes the information encoded into the temporal patterns of blood
insulin. We performed hyperinsulinemic-euglycemic clamp experiments and found
that, in the liver, all temporal patterns of insulin are encoded into the insulin
receptor, and downstream molecules selectively decode them through AKT. S6K
selectively decodes the additional secretion information. G6Pase interprets the
basal secretion information through FoxO1, while GSK3beta decodes all secretion
pattern information. Mathematical modeling revealed the mechanism via differences
in network structures and from sensitivity and time constants. Given that almost
all hormones exhibit distinct temporal patterns, temporal coding may be a general
principle of system homeostasis by hormones.
PMID- 29960884
TI - MHCflurry: Open-Source Class I MHC Binding Affinity Prediction.
AB - Predicting the binding affinity of major histocompatibility complex I (MHC I)
proteins and their peptide ligands is important for vaccine design. We introduce
an open-source package for MHC I binding prediction, MHCflurry. The software
implements allele-specific neural networks that use a novel architecture and
peptide encoding scheme. When trained on affinity measurements, MHCflurry
outperformed the standard predictors NetMHC 4.0 and NetMHCpan 3.0 overall and
particularly on non-9-mer peptides in a benchmark of ligands identified by mass
spectrometry. The released predictor, MHCflurry 1.2.0, uses mass spectrometry
datasets for model selection and showed competitive accuracy with standard tools,
including the recently released NetMHCpan 4.0, on a small benchmark of affinity
measurements. MHCflurry's prediction speed exceeded 7,000 predictions per second,
396 times faster than NetMHCpan 4.0. MHCflurry is freely available to use,
retrain, or extend, includes Python library and command line interfaces, may be
installed using package managers, and applies software development best
practices.
PMID- 29960886
TI - IKZF1 Enhances Immune Infiltrate Recruitment in Solid Tumors and Susceptibility
to Immunotherapy.
AB - Immunotherapies are some of the most promising emergent treatments for several
cancers, yet there remains a majority of patients who do not benefit from them
due to immune-resistant tumors. One avenue for enhancing treatment for these
patients is by converting these tumors to an immunoreactive state, thereby
restoring treatment efficacy. By leveraging regulatory networks we previously
characterized in autoimmunity, here we show that overexpression of the master
regulator IKZF1 leads to enhanced immune infiltrate recruitment and tumor
sensitivity to PD1 and CTLA4 inhibitors in several tumors that normally lack
IKZF1 expression. This work provides proof of concept that tumors can be rendered
susceptible by hijacking immune cell recruitment signals through molecular master
regulators. On a broader scale, this work also demonstrates the feasibility of
using computational approaches to drive the discovery of novel molecular
mechanisms toward treatment.
PMID- 29960885
TI - Four Key Steps Control Glycolytic Flux in Mammalian Cells.
AB - Altered glycolysis is a hallmark of diseases including diabetes and cancer.
Despite intensive study of the contributions of individual glycolytic enzymes,
systems-level analyses of flux control through glycolysis remain limited. Here,
we overexpress in two mammalian cell lines the individual enzymes catalyzing each
of the 12 steps linking extracellular glucose to excreted lactate, and find
substantial flux control at four steps: glucose import, hexokinase,
phosphofructokinase, and lactate export (and not at any steps of lower
glycolysis). The four flux-controlling steps are specifically upregulated by the
Ras oncogene: optogenetic Ras activation rapidly induces the transcription of
isozymes catalyzing these four steps and enhances glycolysis. At least one
isozyme catalyzing each of these four steps is consistently elevated in human
tumors. Thus, in the studied contexts, flux control in glycolysis is concentrated
in four key enzymatic steps. Upregulation of these steps in tumors likely
underlies the Warburg effect.
PMID- 29960887
TI - Dissecting FcgammaR Regulation through a Multivalent Binding Model.
AB - Many immune receptors transduce activation across the plasma membrane through
their clustering. With Fcgamma receptors (FcgammaRs), this clustering is driven
by binding to antibodies of differing affinities that are in turn bound to
multivalent antigen. As a consequence of this activation mechanism, accounting
for and rationally manipulating immunoglobulin (Ig)G effector function is
complicated by, among other factors, differing affinities between FcgammaR
species and changes in the valency of antigen binding. In this study, we show
that a model of multivalent receptor-ligand binding can effectively account for
the contribution of IgG-FcgammaR affinity and immune complex valency. This model
in turn enables us to make specific predictions about the effect of immune
complexes of defined composition. In total, these results enable both rational
immune complex design for a desired IgG effector function and the deconvolution
of effector function by immune complexes.
PMID- 29960888
TI - The Significance of the Female Orgasm: A Nationally Representative, Dyadic Study
of Newlyweds' Orgasm Experience.
AB - BACKGROUND: Self-reported orgasm, perception of partner's orgasm, and
misperception of partner's orgasm have each been correlated with individual
sexual and relationship satisfaction, but these associations have rarely included
dyadic data, have not fully accounted for potentially confounding variables such
as sexual communication, and have never been simultaneously studied with a
nationally representative sample. AIM: To provide a more complete picture of how
the orgasmic experience within the heterosexual couple influences individual and
partner sexual and relationship satisfaction. METHODS: Using a nationally
representative dyadic sample of 1,683 newlywed heterosexual couples, a structural
equation model was estimated to test associations between husband and wife self
reported orgasm frequency, husband and wife report of the other partner's orgasm
frequency, and husband and wife misperception of their partner's orgasm
frequency, as correlates of relationship and sexual satisfaction. OUTCOMES: Both
husband and wife completed the Couples Satisfaction Index to assess their own
relationship satisfaction, and completed a sexual satisfaction instrument
designed for the CREATE study. RESULTS: 87% of husbands and 49% of wives reported
consistently experiencing orgasm. 43% of husbands misperceived how often their
wives experienced orgasm. The final structural equation model, including sexual
communication, explained moderate amounts of variance in wives' and husbands'
relationship satisfaction, and a high level of variance for wives' and husbands'
sexual satisfaction. Wives' relationship satisfaction was positively associated
with wives' and husbands' sexual communication. Wives' sexual satisfaction was
positively associated with self-reported orgasm frequency, and both wives' and
husbands' sexual communication. Husbands' relationship satisfaction was
positively associated with husbands' and wives' sexual communication. Husbands'
sexual satisfaction was positively associated with husbands' perception of wives'
orgasm frequency, and both husbands' and wives' sexual communication. CLINICAL
TRANSLATION: When counseling couples, clinicians should give particular attention
to the wife's orgasm experiences, to potentially help both husbands and wives
have higher sexual satisfaction. STRENGTHS & LIMITATIONS: Strengths of this study
include the use of a nationally representative sample and dyadic data.
Limitations include cross-sectional data, and the assessment of sexual
experiences only in newlywed couples. CONCLUSION: Wives' orgasm (wives' self
report of frequency and husbands' perception of frequency) has a unique positive
association with sexual satisfaction, even after taking into account other
aspects of the orgasm experience and sexual communication. Leonhardt ND,
Willoughby BJ, Busby DM, et al. The Significance of the Female Orgasm: A
Nationally Representative, Dyadic Study of Newlyweds' Orgasm Experience. J Sex
Med 2018;15:1140-1148.
PMID- 29960889
TI - Adult Buried Penis Repair with Escutcheonectomy and Split-Thickness Skin
Grafting.
AB - AIM: To describe a technique for surgical correction of adult buried penis,
including a technique for skin graft harvesting from the escutcheonectomy
specimen itself, with an emphasis on remaining open questions in the literature.
METHODS: We present our method for surgical correction of adult buried penis with
a review of the literature. MAIN OUTCOME MEASURE: Components of successful buried
penis repair include return of directed voiding, elimination of local skin
inflammation and infection, improvement in hygiene, return of sexual functioning,
cosmesis, and patient satisfaction. To date, there are no broadly accepted tools
for comprehensive measurement of outcomes after buried penis repair. RESULTS:
Adult buried penis repair is generally associated with excellent rates of
satisfaction and improvement in functioning. Currently available data are
extremely limited; however, they do suggest that, when in doubt, more aggressive
debridement of diseased tissue combined with split-thickness skin grafting may
provide superior outcomes. Split-thickness skin grafts are associated with
excellent rates of successful graft take, even in cases of severe preoperative
pathology and patient comorbidity. Although these grafts come at the cost of some
increased surgical morbidity, they are associated with low rates of major
complications. Morbidity can be further significantly decreased by harvesting the
graft from the excised escutcheon itself, a technique that we present here.
CONCLUSION: Surgical correction of adult buried penis is safe and effective;
however, future work is required to further optimize outcomes and reduce surgical
morbidity. Strother MC, Skokan AJ, Sterling ME, et al. Adult Buried Penis Repair
with Escutcheonectomy and Split-Thickness Skin Grafting. J Sex Med 2018;15:1198
1204.
PMID- 29960891
TI - Erectile Dysfunction and Depression: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Some studies have reported that exposure to depression increases the
risk of erectile dysfunction (ED), whereas others have observed no association.
Moreover, additional studies have reported that exposure to ED increases the risk
of depression. AIM: To identify and quantitatively synthesize all studies
evaluating the association between ED and depression and to explore factors that
may explain differences in the observed association. METHODS: We conducted a
systematic review and meta-analysis. We searched Medline, Ovid Embase, and the
Cochrane Library through October 2017 for studies that had evaluated the
association between ED and depression. Studies were included in accordance with
Patient Population or Problem, Intervention, Comparison, Outcomes, and Setting
(PICOS) inclusion criteria. OUTCOMES: The odds ratio (OR) was regarded as the
effect size, and the heterogeneity across studies was assessed using the I2
statistic. RESULTS: We identified 49 eligible publications. The pooled OR for
studies evaluating depression exposure and risk of ED was 1.39 (95% CI: 1.35
1.42; n = 46 publications with 48 studies). Although we observed large
heterogeneity (I2 = 93.6%), subgroup analysis indicated that it may have been as
a result of variations in study design, comorbidities, ED assessment, depression
assessment, the source of the original effect size, etc. No significant
publication bias was observed (P = .315), and the overall effect size did not
change by excluding any single study. The pooled OR for studies evaluating ED
exposure and risk of depression was 2.92 (95% CI: 2.37-3.60; n = 5 publications
with 6 studies). No significant heterogeneity (P < .257, I2 = 23.5%) or
publication bias (P = .260) was observed. CLINICAL IMPLICATIONS: Patients
reporting ED should be routinely screened for depression, whereas patients
presenting with symptoms of depression should be routinely assessed for ED.
STRENGTHS AND LIMITATIONS: There are several strengths to this study. First,
evaluations of the association between ED and depression are timely and relevant
for clinicians, policymakers, and patients. Second, we intentionally conducted 2
meta-analyses on the association, allowing us to include all potentially relevant
studies. However, our study also possesses some limitations. First, the OR is a
measure of association that only reveals whether an association is present. Thus,
this study was unable to determine the direction of causality between ED and
depression. Second, the high heterogeneity among studies makes it difficult to
generalize the conclusions. CONCLUSION: This study demonstrates an association
between depression and ED. Policymakers, clinicians and patients should attend to
the association between depression and ED. Liu Q, Zhang Y, Wang J, et al.
Erectile dysfunction and depression: A systematic review and meta-analysis. J Sex
Med 2018;15:1073-1082.
PMID- 29960890
TI - Surgeons Corner: Cavernoscopy for Rear Tip Extender Removal.
AB - INTRODUCTION: Cavernoscopy (using a cystoscope in the corpora) is traditionally
used to retrieve rear tip extenders (RTEs) that are embedded at the time of
removal or replacement of inflatable penile prostheses. AIM: To describe
indications and techniques of cavernoscopy. METHODS: We describe our preferred
method of cavernoscopy to retrieve retained rear tips and present a thorough
review of the literature regarding cavernoscopy. MAIN OUTCOME MEASURE: Ability of
cavernoscopy to retrieve embedded rear tips without causing complications.
RESULTS: Cavernoscopy is feasible anecdotally in case reports, but other less
invasive methods of retrieving RTEs seem to have similar efficacy. CONCLUSION:
Cavernoscopy is a technically feasible procedure that can be attempted as part of
a stepwise algorithm for removing retained RTEs. Thirumavalavan N, Hoover CRV,
Gross MS. Surgeons Corner: Cavernoscopy for Rear Tip Extender Removal. J Sex Med
2018;15:1195-1197.
PMID- 29960892
TI - Transcriptomic analysis reveals the molecular adaptation to NaCl stress in
Zostera marina L.
AB - The seagrass Zostera marina L. shows optimal growth in marine water and reduced
growth under low salinity conditions. However, little is known about the
molecular mechanisms underlying its adaptation to high salinity in Z. marina. In
this study, transcriptomic analyses were performed using RNA-seq of the following
two groups with different NaCl content: the CK group (seagrasses grown in the
absence of NaCl) and the NaCl group (seagrasses grown in the presence of 400 mM
NaCl for 6 h). Approximately 316 million high-quality reads were generated, and
87.9% of the data were mapped to the reference genome. Moreover, differentially
expressed genes between the CK and NaCl groups were identified. According to a
functional analysis, the up-regulated genes after the NaCl treatment were
significantly enriched in nitrogen metabolism, calcium signalling and DNA
replication while the down-regulated genes were significantly enriched in
photosynthesis. A comparative transcriptomic analysis detected many
differentially expressed genes and pathways required for adaptation to NaCl
stress, providing a foundation for future studies investigating the molecular
mechanisms of salt adaptation in Z. marina. We discuss how molecular changes in
these processes may have contributed to the NaCl adaptation.
PMID- 29960893
TI - Tigecycline in the treatment of multidrug-resistant Acinetobacter baumannii
meningitis: Results of the Ege study.
AB - OBJECTIVES: In this study we retrospectively reviewed A. baumannii meningitis
cases treated with tigecycline including regimens and evaluated the efficacy of
tigecycline in the therapy. PATIENTS AND METHODS: Study was performed in seven
tertiary-care educational hospitals from five cities of Turkey and one center
from France. We extracted data and outcomes of all adult (aged >18) patients with
culture proven A. baumannii meningitis treated with tigecycline including
antibiotic therapy until April 2016. RESULTS: A total of 23 patients (15 male and
eight female) fulfilled our inclusion criteria. All Acinetobacter strains were
carbapenem-resistant and susceptible to tigecycline. Six cases received
tigecycline monotherapy while 17 received tigecycline including combination
therapy (10 with colistin, 4 with netilmicin, 3 with amikacin, 4 with meropenem).
Seven of 23 cases (30%) died during the tigecycline including therapy (1 in
monotherapy, 4 in colistin, 2 in netilmicin, 1 amikacin, one case received
tigecycline + netilmicin followed by tigecycline + colistin). Hence, overall end
of treatment (EOT) success was 70%. However, since further 27% died due to
additional nosocomial infections, overall clinical success (relieved symptoms at
the EOT and one-month post-therapy survival without any relapse or reinfection)
decreased to 43%. CONCLUSION: We conclude that tigecycline may be an alternative
in the salvage treatment of nosocomial multidrug-resistant Acinetobacter spp.
meningitis. Acinetobacter spp. Meningitis.
PMID- 29960894
TI - A scoping review of trials of interventions led or delivered by cancer nurses.
AB - BACKGROUND: Advances in research and technology coupled with an increased cancer
incidence and prevalence have resulted in significant expansion of cancer nurse
role, in order to meet the growing demands and expectations of people affected by
cancer (PABC). Cancer nurses are also tasked with delivering an increasing number
of complex interventions as a result of ongoing clinical trials in cancer
research. However much of this innovation is undocumented, and we have little
insight about the nature of novel interventions currently being designed or
delivered by cancer nurses. OBJECTIVES: To identify and synthesise the available
evidence from clinical trials on interventions delivered or facilitated by cancer
nurses. DATA SOURCES AND REVIEW METHODS: A systematic review of randomised
controlled trials (RCT), quasi-RCTs and controlled before and after studies (CBA)
of cancer nursing interventions aimed at improving the experience and outcomes of
PABC. Ten electronic databases (CENTRAL, MEDLINE, AMED, CINAHL, EMBASE,
Epistemonikos, CDSR, DARE, HTA, WHO ICTRP) were searched between 01 January 2000
and 31 May 2016. No language restrictions were applied. Bibliographies of
selected studies and relevant Cochrane reviews were also hand-searched.
Interventions delivered by cancer nurses were classified according to the OMAHA
System. Heat maps were used to highlight the volume of evidence available for
different cancer groups, intervention types and stage of cancer care continuum.
RESULTS: The search identified 22,450 records; we screened 16,169 abstracts and
considered 925 full papers, of which 214 studies (247,550 participants) were
included in the evidence synthesis. The majority of studies were conducted in
Europe (n = 79) and USA (n = 74). Interventions were delivered across the cancer
continuum from prevention and risk reduction to survivorship, with the majority
of interventions delivered during the treatment phase (n = 137). Most studies
(131/214) had a teaching, guidance or counselling component. Cancer nurse
interventions were targeted at primarily breast, prostate or multiple cancers. No
studies were conducted in brain, sarcoma or other rare cancer types. The majority
of the studies (n = 153) were nurse-led and delivered by specialist cancer nurses
(n = 74) or advanced cancer nurses (n = 29), although the quality of reporting
was poor. CONCLUSIONS: To the best of our knowledge, this is the first review to
synthesise evidence from intervention studies across the entire cancer spectrum.
As such, this work provides new insights into the nature of the contribution that
cancer nurses have made to evidence-based innovations, as well as highlighting
areas in which cancer nursing trials can be developed in the future.
PMID- 29960895
TI - Nurse perceptions of person-centered handovers in the oncological inpatient
setting: A qualitative study.
AB - BACKGROUND: Deficient communication during shift change can cause negative
patient outcomes and hinder person-centeredness in care. Person-centered handover
is performed together with the patient at bedside, with the intention of
providing a safe and efficient handover while promoting patient participation.
The knowledge about nurse perspectives on handover models that involve patient
participation is sparse. OBJECTIVE: To describe registered nurses' perceptions of
person-centered handover in an oncological inpatient setting. DESIGN: A
qualitative interview study. SETTING: The study was undertaken at two oncological
inpatient wards at the Karolinska University Hospital, Stockholm, where person
centered handover was implemented in 2015. PARTICIPANTS: Registered nurses who
had worked at the wards for at least six months. We aimed for a full sample
investigation. All eligible nurses (n = 13) were approached, and 11 chose to
participate. Participants' age ranged from 23 to 60 years, the mean work
experience was 10 years, and 4 out of 11 nurses were oncology nurse specialists.
METHODS: Semi-structured interviews were performed by an independent researcher.
The data was analyzed using content analysis with an inductive approach. RESULTS:
Three main themes with ten subsequent subthemes emerged from the data. The main
themes were: clinical communication and assessment; opportunity for patient
participation; consequences for nursing care. In general, the nurses were
positive towards person-centered handover, but they expressed concerns regarding
patients' integrity and insecurities regarding bedside communication. All nurses
described how they aimed at enhancing patient participation and viewed person
centered handover as an opportunity, but still perceived it difficult to succeed
due to drawbacks and factors hindering nursing care. Overall, the nurses were
positive regarding the involvement of patients in the handover procedure.
Information provision from nurse to patient, as opposed to information exchange,
was predominant. CONCLUSIONS: The intentions of person-centered handovers
differed from the way it was actually performed, especially in regards to the
obtained levels of patient participation, as described by nurses. Professional
insecurity in relation to bedside communication with patients and their visitors
is a novel finding that should be considered when implementing person-centered
handovers. Overall, the perceptions of person-centered handovers, as expressed by
the nurses, enhance our understanding of what to consider when implementing the
model and why compliance may vary.
PMID- 29960896
TI - Genetic and evolutionary determinants of human population variation in immune
responses.
AB - Humans display remarkable immune response variation when exposed to identical
immune challenges. However, our understanding of the genetic, evolutionary, and
environmental factors that impact this inter-individual and inter-population
immune response heterogeneity is still in its early days. In this review, we
discuss three fundamental questions concerning the recent evolution of the human
immune system: the degree to which individuals from different populations vary in
their innate immune responses, the genetic variants accounting for such
differences, and the evolutionary mechanisms that led to the establishment of
these variants in modern human populations. We also discuss how past selective
events might have contributed to the uneven distribution of immune-related
disorders across populations.
PMID- 29960897
TI - Lipocalin-2 contributes to experimental atherosclerosis in a stage-dependent
manner.
AB - BACKGROUND AND AIMS: Lipocalin-2 (Lcn2) is a glycoprotein which can be secreted
by immune cells. Several studies in humans have suggested Lcn2 can be used as a
biomarker for the detection of unstable atherosclerotic lesions, partly as it is
known to interact with MMP-9. METHODS: In this study, we generated Ldlr-/-Lcn2-/-
mice to assess the functional role of Lcn2 in different stages of
atherosclerosis. Atherosclerotic lesions were characterized through histological
analysis and myeloid cell populations were examined using flow cytometry.
RESULTS: We show that Ldlr-/-Lcn2-/- mice developed larger atherosclerotic
lesions during earlier stages of atherosclerosis and had increased circulating
Ly6Chi inflammatory monocytes compared to Ldlr-/- mice. Advanced atherosclerotic
lesions from Ldlr-/-Lcn2-/- mice had decreased necrotic core area, suggesting
Lcn2 deficiency may affect lesion stability. Furthermore, MMP-9 activity was
diminished in plaques from Ldlr-/-Lcn2-/- mice. CONCLUSIONS: Altogether, these
findings suggest that Lcn2 deficiency promotes lesion growth in earlier stages of
the disease while it decreases MMP-9 activity and necrotic core size in advanced
atherosclerosis.
PMID- 29960898
TI - Lipoprotein(a) and apolipoprotein(a) isoform size: Associations with angiographic
extent and severity of coronary artery disease, and carotid artery plaque.
AB - BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is an emerging genetic risk factor
for cardiovascular disease (CVD). We examined whether plasma Lp(a) concentration
and apolipoprotein(a) [apo(a)] isoform size are associated with extent and
severity of coronary artery disease (CAD), and the presence of carotid artery
plaque. METHODS: We included in our study male participants (n = 263) from a
cohort with angiographically defined premature CAD (Carotid Ultrasound in
Patients with Ischemic Heart Disease). The angiographic extent and severity of
CAD were determined by the modified Gensini and Coronary Artery Stenosis>=20%
(CAGE) scores. Carotid artery plaque was assessed by bilateral carotid B-mode
ultrasound. Apo(a) isoform size was determined by LPA Kringle IV-2 copy number
(KIV-2 CN). RESULTS: Lp(a) concentration, but not KIV-2 CN, was positively
associated with the Gensini score. The association remained significant following
adjustment for conventional CVD risk factors (all p < 0.05). Lp(a) concentration
and elevated Lp(a) [>=50 mg/dL] were positively associated with the CAGE>=20
score, independent of conventional CVD risk factors. KIV-2 C N Q1 (lowest KIV-2
CN quartile) was associated with CAGE>=20 score and KIV-2 CN, with the CAGE>=20
score in those without diabetes. In multivariate models that included phenotypic
familial hypercholesterolemia or low-density lipoprotein cholesterol, Lp(a)
concentration, but not KIV-2 CN, was independently associated with the Gensini
and CAGE>=20 scores. No significant associations between Lp(a) concentration and
KIV-2 CN with carotid artery plaque were observed. CONCLUSIONS: Lp(a)
concentration, but not apo(a) isoform size, is independently associated with
angiographic extent and severity of CAD. Neither Lp(a) nor apo(a) isoform size is
associated with carotid artery plaque.
PMID- 29960899
TI - Breaking bad news: How to cope.
PMID- 29960900
TI - Association between non-variceal spontaneous portosystemic shunt and outcomes
after TIPS in cirrhosis.
AB - BACKGROUND: Whether pre-existing nonvariceal spontaneous portosystemic shunts
(SPSSs) in cirrhotic patients affect outcomes after transjugular intrahepatic
portosystemic shunt (TIPS) and whether they need to be closed remains unclear.
AIM: To assess the effects of the presence or embolization of SPSSs on outcomes
after TIPS for cirrhosis. METHODS: From January 2004 to December 2014, 903
consecutive cirrhotic patients who underwent TIPS in a tertiary-care center were
included, of which 715 patients had no SPSS (N-SPSS group), 144 patients had an
SPSS without embolization (SPSS group), and 44 had an SPSS with embolization
(SPSS + E group). RESULTS: During a median follow-up period of 27.7 months, 368
(41%) patients experienced overt hepatic encephalopathy (OHE), 256 (28%)
experienced clinical relapse, 164 (18%) developed shunt dysfunction, and 379
(42%) died. The SPSS group had a higher risk of OHE compared with the N-SPSS and
SPSS + E groups (adjusted HR [95%CI]: N-SPSS vs SPSS vs SPSS + E: 1 vs 1.36 [1.06
1.75] vs 0.77 [0.46-1.29]; p = 0.027). In stratification analysis, a higher risk
of OHE was only observed in patients with a large SPSS (SPSS diameter >=6 mm) but
not a small SPSS. Additionally, SPSS embolization was associated with a lower
risk of OHE among patients with a large SPSS (adjust HR = 0.51; 95% CI: 0.29
0.91; p = 0.034). The risks of clinical relapse (p = 0.584), shunt dysfunction (p
= 0.267), and mortality (p = 0.4743) did not significantly differ among groups.
CONCLUSIONS: Among cirrhotic patients undergoing TIPS, a pre-existing large SPSS
was associated with a higher risk of OHE, which could be decreased by SPSS
embolization. There was no clear association between the presence/embolization of
an SPSS and post-TIPS clinical relapse, shunt dysfunction or mortality.
PMID- 29960902
TI - In vivo identification of novel TGIF2LX target genes in colorectal adenocarcinoma
using the cDNA-AFLP method.
AB - BACKGROUND AND STUDY AIMS: Homeobox-containing genes are composed of a group of
regulatory genes encoding transcription factors involved in the control of
developmental processes. The homeodomain proteins could activate or repress the
expression of downstream target genes. This study was conducted to in vivo
identify the potential target gene(s) of TGIF2LX in colorectal adenocarcinoma.
METHODS: A human colorectal adenocarcinoma cell line, SW48, was transfected with
the recombinant pEGFPN1-TGIF2LX. The cells were injected subcutaneously into the
flank of the three groups of 6-week-old female athymic C56BL/6 nude mice (n = 6
per group). The transcript profiles in the developed tumours were investigated
using the cDNA amplified fragment length polymorphism (cDNA-AFLP) technique.
RESULTS: The real-time RT-PCR and DNA sequencing data for the identified genes
indicated that the N-terminal domain-interacting receptor 1 (Nir1) gene was
suppressed whereas Nir2 and fragile histidine triad (FHIT) genes were upregulated
followed by the overexpression of TGIF2LX gene. CONCLUSION: Downregulation of
Nir1 and upregulation of Nir2 and FHIT genes due to the overexpression of TGIF2LX
suggests that the gene plays an important role as a suppressor in colorectal
adenocarcinoma.
PMID- 29960901
TI - Management of haemostatic alterations and associated disorders in cirrhosis in
Spain: A national survey.
AB - BACKGROUND: Knowledge of haematological abnormalities in cirrhosis has greatly
improved in recent years. AIMS: To evaluate how Spanish Digestive Disease
specialists manage haemostatic alterations and associated disorders in patients
with cirrhosis. METHODS: All members of the Spanish Association for the Study of
the Liver and Spanish Society of Digestive Pathology were invited to fill in a
web-based questionnaire. RESULTS: 135 professionals, 93 hepatologists and 42 non
hepatologists responded to the survey. The concept of rebalanced haemostasis was
known by 74.8% of them. Most specialists corrected the INR and thrombocytopenia
before invasive procedures with moderate risk of bleeding or major surgery and in
severe gastrointestinal bleeding. The threshold of platelets and, especially, INR
used to administer blood products varied greatly. Pharmacological prophylaxis of
venous thromboembolism prevailed, but it was highly dependent on the INR and
platelet figures. Most participants initiated anticoagulation regardless of the
degree of portal vein thrombosis, even in patients ineligible for
transplantation. In potential candidates, only 56% maintained it indefinitely or
until liver transplantation. No major differences between hepatologists and non
hepatologists were found. CONCLUSIONS: A significant variability and certain
deviation from current guidelines was observed among Spanish Digestive Disease
specialists regarding management of haemostatic alterations and associated
disorders in cirrhosis.
PMID- 29960903
TI - Communicative eye contact signals a commitment to cooperate for young children.
AB - Making commitments to cooperate facilitates cooperation. There is a long-standing
theoretical debate about how promissory obligations come into existence, and
whether linguistic acts (such as saying "I promise") are a necessary part of the
process. To inform this debate we experimentally investigated whether even
minimal, nonverbal behavior can be taken as a commitment to cooperate, as long as
it is communicative. Five- to 7-year-old children played a Stag Hunt coordination
game in which they needed to decide whether to cooperate or play individually.
During the decision-making phase, children's partner made either ostensive,
communicative eye contact or looked non-communicatively at them. In Study 1 we
found that communicative looks produced an expectation of collaboration in
children. In Study 2 we found that children in the communicative look condition
normatively protested when their partner did not cooperate, thus showing an
understanding of the communicative looks as a commitment to cooperate. This is
the first experimental evidence, in adults or children, that in the right
context, communicative, but not non-communicative, looks can signal a commitment.
PMID- 29960904
TI - Robust carbon nanotube foam for efficient electromagnetic interference shielding
and microwave absorption.
AB - Lightweight and robust carbon nanotube (CNT)/chitosan (CS) foams were assembled
by a facile unidirectional freeze-drying method in this work. The CNT/CS foam
exhibited an excellent electromagnetic interference (EMI) shielding effectiveness
(SE) of 37.6 dB while the density was only 17.6 mg.cm-3, and thus the
corresponding specific SE was up to 8556 dB.cm2.g-1. The superior EMI shielding
performance was mainly attributed to the perfect conductive networks.
Additionally, the absorption coefficient of CNT/CS foam was up to 81.73% under
high EMI SE of 37.6 dB, which was remarkable among the reported EMI shielding
materials with comparable EMI shielding level. More importantly, the addition of
CS significantly increased the compressive strength and modulus of CNT/CS foam to
34.1 KPa and 177.1 KPa, which were 84% and 149% higher than those for the pure
CNT foam, respectively. These results indicate that the CNT/CS foam is an ideal
high-efficient EMI shielding material, which has high potential applications in
the fields of aerospace, automotive, and electronic devices.
PMID- 29960905
TI - Fabrication of three-dimensional composite textile electrodes by metal-organic
framework, zinc oxide, graphene and polyaniline for all-solid-state
supercapacitors.
AB - Textile electrode materials have attracted intense attention in the flexible
supercapacitor field due to their flexibility, light weight, hierarchical
porosity and mechanical robustness. However, their electrochemical performance is
not good due to the low conductivity, ineffective ion diffusion and small
electroactive surface area. In this study, a three-dimensional (3D) textile
electrode material was constructed by utilizing ZIF-8 (Zeolitic Imidazolate
Framework), metal oxides, conductive polymers and graphene sheets. The
polyaniline/ZnO/ZIF-8/graphene/polyester textile electrode exhibited good
electrochemical performance with a high areal capacitance of 1.378 F/cm2 at 1
mA/cm2 and high stability under different mechanical deformations. A flexible all
solid-state symmetric supercapacitor device was further fabricated, which can
provide a high energy density of 235 MUWh/cm3 at a power density of 1542 MUW/cm3.
PMID- 29960906
TI - Novel electrochemical synthesis of copper oxide nanoparticles decorated graphene
beta-cyclodextrin composite for trace-level detection of antibiotic drug
metronidazole.
AB - Over the past decades, the synthesis of inorganic and organic nanocomposites has
received much attention in the range of fields including electroanalysis of
organic chemicals. In this regard, we have prepared copper oxide nanoparticle
(CuO NPs) decorated graphene/beta-cyclodextrin (GR-beta-CD) composites using a
simple electrochemical methodology, where the CuO NPs are electrodeposited on GR
beta-CD composite modified electrodes. A stable GR-beta-CD composite was prepared
by sonication of GR in beta-CD aqueous solution. As-prepared GR-beta-CD/CuO NPs
composites were characterized by the high-resolution scanning electron
microscopy, X-ray diffraction, and Raman spectroscopy. Cyclic voltammetry results
reveal that the GR-beta-CD/CuO NPs composite modified electrode exhibits an
excellent catalytic activity and lower reduction potential towards the
electrochemical detection of metronidazole (MTZ) over other modified electrodes
including GR, GR-beta-CD, and CuO NPs. Under optimized conditions, amperometry
was used for the determination of MTZ using GR-beta-CD/CuO NPs composite modified
electrodes. The response of MTZ using the composite electrodes was linear over
the range from 0.002 to 210.0 uM. This sensor showed the lowest limit of
detection of 0.6 nM and was much lower than the previously reported MTZ sensors.
In addition, the sensor is highly sensitive, selective and durable in the
presence of a range of potentially interfering electroactive compounds.
PMID- 29960907
TI - Crumpled graphene balls as rapid and efficient adsorbents for removal of copper
ions.
AB - A novel, three-dimensional (3D), self-supporting material-the crumpled graphene
ball-was developed using an aerosol capillary approach. The resultant crumpled
graphene-ball architecture showed a self-supporting, 3D network microstructure
with plenty of ridges and wrinkles. Due to their unique structural
characteristics, the 3D balls exhibited a rapid adsorption rate and superior
adsorption capacity toward the copper ion (Cu2+). It was noted that the
adsorption capacity for Cu2+ reached about 224.56 mg/g within 2 min. A high
adsorption capacity, fast adsorption kinetics, excellent regeneration and
reusability characteristics, and the ease of materials processing make these
crumpled graphene balls ideal candidates for heavy metal ion decontamination in
practical application.
PMID- 29960908
TI - Synthesis of Eu2+/Eu3+ Co-Doped Gallium oxide nanocrystals as a full colour
converter for white light emitting diodes.
AB - Eu2+ and Eu3+ co-doped Ga2O3 nanocrystals (Ga2O3:Eu NCs) were synthesized in an
organic phase at a low reaction temperature of 300 degrees C. The surface of
Ga2O3:Eu NCs was passivated by oleylamine (OAm) and acetylacetone (acac). The
coexistence of Eu2+ and Eu3+ as well as passivation by acac and OAm enable Ga2O3
to be excited in the broad spectral range of 200-500 nm. The broadened absorption
band is attributed to the strong acac -> Ln(III) ligand to the metal charge
transfer transition at ~370 nm, Eu(III) f-f allowed 7F0 -> 5L6 transition at 395
nm, and 7F0 -> 5D2 transition at 465 nm, as well as the efficient electronic
transition of Eu(II) 4f -> 5d at ~400 nm. Under near-ultraviolet excitation,
white light emission can be achieved by combining orange-red light from f-f
electronic transition of Eu(III) with blue-green-yellow light from Ga2O3 oxygen
defects levels. Furthermore, the resultant Ga2O3:Eu NCs with optimized quantum
yield of 14.5% were coated onto 395 nm near-ultraviolet chips to fabricate a
white light emitting diode. It exhibits a luminous efficiency of 34 lm/W, CIE
colour coordinate of (0.2964, 0.2831) and high colour rendering index of 80.
PMID- 29960909
TI - Facile construction of ultrafine nickel-zinc oxyphosphide nanosheets as high
performance electrocatalysts for oxygen evolution reaction.
AB - Realizing the synthesis of highly efficient electrocatalysts for water splitting
is generally regarded as a significant section in the field of renewable energy
conversion and storage but still an intriguing challenge. Here, a series of
transition metal oxyphosphides with ultrafine nanosheet structure have been
successfully created as high-performance electrocatalysts for oxygen evolution
reaction (OER). Taking advantages of the abundant surface defects, modified
electronic effects, as well as the high surface active areas, we herein
successfully construct a novel class of highly-efficient electrocatalysts, and
the resultant NiZn oxyphosphide nanosheets (NiZnP NSs) can exhibit relatively low
overpotentials of 290 and 332 mV to achieve the current densities of 10 and 50 mA
cm-2 for OER, respectively, outperforming most of non-noble metal
electrocatalysts. More impressively, such NiZnP NSs can also retain high
catalytic activity with negligible composition and structure variations after
long-term electrochemical test. This work provides prospects to construct highly
efficient, earth abundant, and ultra-durable two-dimensional (2D)
electrocatalysts for water splitting.
PMID- 29960910
TI - Vesicle formation by cholesterol based hydrazone tethered amphiphiles: Stimuli
responsive dissipation of self-assembly.
AB - Stimuli are one of the key parameters to achieve a control over the
association/dissociation of molecular tectons in self-assemblies. In this present
article, we synthesized cholesterol based pH-sensitive hydrazone-tailored low
molecular mass amphiphiles (CBH-1-3). The hydrazone residue was modified by
varying the carbonyl moieties from aldehyde (benzaldehyde (CBH-1), p
dimethylaminobenzaldehyde (CBH-2)) to ketone (benzophenone (CBH-3)). Microscopic
and spectroscopic characterizations were carried out to investigate the pattern
of self-aggregation and its morphology. Among these amphiphiles, CBH-1 and CBH-2
were found to form vesicular aggregates through H-type aggregation in 1:3 v/v,
DMSO-water having dimension of around 50-120 nm in the case of CBH-1 and ~150-250
nm for CBH-2. Moreover, low angle X-ray diffraction (XRD) pattern of the self
aggregates confirmed the formation of bilayer vesicles through highly ordered
lamellar like structure for the hydrazone-tailored amphiphiles. These vesicles
are stable at pH 7.0 and above, however get disassembled at acidic pH (pH < 5.0).
This dissipation of the vesicular self-aggregates because of the cleavage of the
hydrazone bond under acidic environment was investigated by UV-visible, FTIR and
mass spectrometric studies. Moreover, absence of any spherical aggregate in the
transmission electron microscopic (TEM) images of the acid treated vesicles
confirmed its disintegration in acidic medium. Furthermore, dye encapsulation and
its pH-responsive release from the CBH-1 vesicles were tested using doxorubicin
as drug.
PMID- 29960911
TI - Flame retardant and visible light-activated Fe-doped TiO2 thin films anchored to
wood surfaces for the photocatalytic degradation of gaseous formaldehyde.
AB - Flame retardant and visible light-activated Fe-doped TiO2 thin films were
anchored to wood surfaces by a facile precipitation method for the photocatalytic
degradation of gaseous formaldehyde. All of the as-prepared TiO2 thin films
exhibited the anatase crystal structure and grew on the wood surfaces by the
aggregation of nanoparticles with diameters ranging from 11 to 16 nm. The UV-vis
diffuse reflectance spectroscopy (UV-vis DRS) results showed that the presence of
a small amount of iron ions in the TiO2 matrix could significantly extend the
optical responses in the UV to visible region. Compared to the pure TiO2/wood
samples, the Fe-doped TiO2/wood samples exhibited higher photocatalytic
activities under visible light irradiation. The optimum nFe/nTi molar ratio was
2.0 at. %. The electron spin resonance (ESR) tests further confirmed that the
active oxygen species of OH and O2- that were generated on the Fe-doped TiO2/wood
samples under visible light irradiation are responsible for the degradation of
formaldehyde. The Fe-doped TiO2 samples also exhibited high stability and
reusability after 6 cycles. Additionally, the limiting oxygen index of the
original wood increased from 24.8% to 33.9% after it was coated with Fe-doped
TiO2 thin films, indicating a significant improvement in its flame resistance.
PMID- 29960912
TI - Morphology control of shell-crosslinked polymer particles prepared by photo
induced shell-selective crosslinking approach via dispersed state control.
AB - HYPOTHESIS: Morphology control of polymer particles is of great importance for
creating functional particulate materials. Photoinduced shell-selective
crosslinking approach with spherical polymer particles has been previously
developed in a dispersed state, in which the polymer particles could rotate
freely, yielding hollow polymer particles after removal of non-crosslinked
polymers because photoinduced crosslinking occurred for the entire particle
surface. This insight prompted the question of whether non-spherical particles
can be obtained if particle rotation is restricted and photoirradiation occurs
for only part of the shell region. EXPERIMENTS: Herein, we developed a facile
approach for morphology control of polymer particles prepared by photoinduced
shell-selective crosslinking of spherical polymer particles bearing photoreactive
cinnamoyl groups by regulating the dispersed state. The morphology of the polymer
particles obtained from the photo-induced shell-selective crosslinking approach
in dispersed or non-dispersed states was confirmed. In-situ real time observation
of forming the non-spherical polymer particles was also performed by optical
microscope. FINDINGS: Hollow and bowl-shaped polymer particles were successfully
obtained from same spherical polymer particles bearing photo-crosslinking groups
in dispersed and non-dispersed states, respectively. The versatility of the
approach was confirmed by using various comonomers. Furthermore, post
functionalization for the polymer particles was also successfully performed using
functional groups derived from the comonomers.
PMID- 29960913
TI - Reduced phytotoxicity of propazine on wheat, maize and rapeseed by salicylic
acid.
AB - Propazine belongs to the triazine herbicide family and widely used in the
farmland for crop production. Recent studies have shown that the residue of
propazine in environment is accumulative. This inevitably results in accumulation
of propazine in crops. Therefore, reduction of propazine toxicity and
accumulation in crops is critically important. In this study, the growth of
wheat, maize and rapeseed was significantly inhibited by 2, 8 and 0.4 mg kg-1
propazine in soils. The chlorophyll content of the three crops also showed
significant decrease, while the electrolyte permeability, a biomarker of cellular
damage, increased in the plant cells. However, when plants were sprayed with 5 mg
L-1 of salicylic acid (SA), the propazine phytotoxicity of the crops was
relieved, with increased chlorophyll content and reduced electrolyte permeability
of all crops. Meanwhile, the activities of peroxidase (POD) and glutathione
transferase (GST) remained lower. The propazine accumulation in the crops and the
residues in the soil were determined by high performance liquid chromatography.
The concentration of propazine in plants and soils treated by SA was less than
that of the untreated control. Six propazine degraded products (derivatives) in
rhizosphere of wheat were characterized using ultraperformance liquid
chromatography with a quadrupole-time-of-flight tandem mass spectrometer. Our
work indicates that the improved growth of crops was possibly due to the
acceleration of propazine degradation by salicylic acid.
PMID- 29960914
TI - Influence of iron plaque on the uptake and accumulation of chromium by rice
(Oryza sativa L.) seedlings: Insights from hydroponic and soil cultivation.
AB - The effects of iron plaque formation on chromium (Cr) uptake and accumulation by
rice seedlings (Oryza sativa L.) were assessed using hydroponic and soil
experiments, where each 3 levels of Fe supplementation were added to Hoagland
solution (0, 30, and 100 mg Fe2+ L-1) and a typical paddy soil (0, 1, and 2 g
Fe2+ kg-1). For each treatment, rice seedlings were exposed to different levels
of Cr as chromate at 0, 0.5, 2, 5, 10, and 20 mg L-1 in solution or 300 mg kg-1
in soil. Low levels of Cr supply (0.5, 2, and 5 mg L-1) promoted root biomass,
while high levels (10 and 20 mg L-1) decreased root and shoot biomass and
undermined the density and integrity of iron plaque. Iron supply significantly
increased the proportion of Cr in iron plaque, but decreased that in rice plants.
The results of hydroponic experiment showed that iron plaque formed with Fe
supply at 100 mg L-1 markedly reduced Cr accumulation in shoots of rice seedlings
when exposure to 10 and 20 mg L-1 Cr. The soil culture experiment also
demonstrated that exogenous Fe addition significantly decreased Cr concentration
in leaf and stem of rice seedlings. These results suggested that iron plaque with
appropriate amount was effective to reduce the uptake and accumulation of Cr in
rice plants, which have strong implication for taking measures to regulate Cr
accumulation in rice grains.
PMID- 29960915
TI - Effects of the water-soluble fraction of diesel oil (WSD) on the fertilization
and development of a sea urchin (Echinometra lucunter).
AB - Considering the high number of accidents with diesel oil spills occurring in the
marine ecosystem, toxicity tests aimed at assessing the effects of this pollutant
on biota are necessary and urgent. Thus, the present study aimed to evaluate the
toxicity of the soluble fraction of diesel oil (WSD) in the fertilization success
of gametes and pluteu larvae of the sea urchin Echinometra lucunter. To do this,
gametes and embryos were exposed to concentrations of 0% (control group), 0.5%,
1.5% and 2.5% of WSD. The fertilization success of exposed gametes and embryos
were reduced significantly when compared to the control group in all tested
concentrations. With this finding, it is evident that diesel oil can be
significantly promoted in the early and adult life stages of a particular
organism, and a better way of evaluating this toxicity is through the analysis of
contaminant effects throughout the reproductive cycle of a species.
PMID- 29960916
TI - Comparing aryltetralin lignan accumulation patterns in four biotechnological
systems of Linum album.
AB - Linum album is a herbaceous plant with medical interest due to its content of
podophyllotoxin (PTOX), an aryltetralin lignan with cytotoxic activity. Previous
studies in our laboratory showed that cell suspension cultures of L. album
produced more PTOX than methoxypodophyllotoxin (6-MPTOX), both lignans being
formed from the same precursor after divergence close to the end of the
biosynthetic pathway. In contrast, the hairy roots produced more 6-MPTOX than
PTOX. Taking into account this variability, we were interested to know if the
lignan profile of an in vitro PTOX-producing L. album plant changes according to
the biotechnological system employed and, if so, if this is due to cell
dedifferentiation and/or transformation events. With this aim, we established
four biotechnological systems: (1) Wild type cell suspensions, (2) transformed
cell suspensions, (3) adventitious roots and (4) hairy roots. We determined the
production of four aryltetralin lignans: PTOX, 6-MPTOX, deoxypodophyllotoxin
(dPTOX) and beta-peltatin. The results show that in vitro plantlets, WT cells and
transformed cells predominantly produced PTOX, production being 11-fold higher in
the plantlets. Otherwise, the adventitious and hairy roots predominantly produced
6-MPTOX, the adventitious roots being the most productive, with MPTOX levels 1.58
fold higher than in transformed roots. We can infer from these results that in
the studied plants, cell differentiation promoted the formation of 6-MPTOX over
PTOX, while transformation did not influence the lignan pattern.
PMID- 29960917
TI - Identification of major matrix metalloproteinase-20 proteolytic processing
products of murine amelogenin and tyrosine-rich amelogenin peptide using a
nuclear magnetic resonance spectroscopy based method.
AB - OBJECTIVE: The aim of this study was to identify major matrix metalloproteinase
20 (MMP20) proteolytic processing products of amelogenin over time and determine
if the tyrosine-rich amelogenin peptide (TRAP) was a substrate of MMP20. DESIGN:
Recombinant15N-labeled murine amelogenin and 13C,15N-labeled TRAP were incubated
with MMP20 under conditions where amelogenin self-assembles into nanospheres.
Digestion products were fractionated by reverse-phase high-performance liquid
chromatography at various time points. Product identification took advantage of
the intrinsic disorder property of amelogenin that results in little change to
its fingerprint 1H-15N heteronuclear single-quantum coherence nuclear magnetic
resonance spectrum in 2% acetic acid upon removing parts of the protein, allowing
cleavage site identification by observing which amide cross peaks disappear.
RESULTS: The primary product in five out of the six major reverse-phase high
performance liquid chromatography bands generated after a 24 h incubation of
murine amelogenin with MMP20 were: S55-L163, P2-L147, P2-E162, P2-A167, and P2
R176. After 72 h these products were replaced with five major reverse-phase high
performance liquid chromatography bands containing: L46-A170, P2-S152, P2-F151,
P2-W45, and short N-terminal peptides. TRAP was completely digested by MMP20 into
multiple small peptides with the initial primary site of cleavage between S16 and
Y17. CONCLUSIONS: Identification of the major MMP20 proteolytic products of
amelogenin confirm a dynamic process, with sites towards the C-terminus more
rapidly attacked than sites near the N-terminus. This observation is consistent
with nanosphere models where the C-terminus is exposed and the N-terminus more
protected. One previously reported end-product of the MMP20 proteolytic
processing of amelogenin, TRAP, is shown to be an in vitro substrate for MMP20.
PMID- 29960918
TI - Marijuana eCHECKUPTO GO: Effects of a personalized feedback plus protective
behavioral strategies intervention for heavy marijuana-using college students.
AB - BACKGROUND: Marijuana use is common among U.S. college students. Liberalization
of marijuana use policies is hypothesized to decrease social norms discouraging
use, which protects against marijuana use. This may increase the importance of
protective behavioral strategies (PBS) to reduce marijuana use harm. METHODS:
This study tested direct and moderated (by sex) program effects of an adapted
version of the Marijuana eCHECKUPTO GO, a web-based marijuana use intervention
providing university-specific personalized feedback (PF) with normative
information and PBS to students attending a university in a state with legalized
adult recreational marijuana. Participants were 298 heavy-using college students
randomly assigned to receive Marijuana eCHECKUPTO GO or strategies for healthy
stress management (HSM). General linear models (GLMs) tested direct program
effects on proximal intervention targets, marijuana use, and use consequences.
Multi-group GLMs then tested the moderating effect of sex on direct intervention
effects. RESULTS: Marijuana eCHECKUPTO GO participants reported decreases in
estimated use prevalence (i.e., descriptive norms), self-reported hours high per
week, days high per week, periods high per week, and weeks high per month. Sex
moderated intervention effects on the use of PBS such that females in the PF
condition increased their use of PBS more than males. CONCLUSION: Results
demonstrate preliminary support for the adapted Marijuana eCHECKUPTO GO in
reducing marijuana use for "heavy college-aged users". Future research should
test adapted Marijuana eCHECKUPTO GO sustained effects over time, and examine
whether program effects on harm reduction manifest after sustained (e.g.,
booster) program implementation.
PMID- 29960920
TI - Gender moderates the association between distress tolerance and alcohol use among
individuals with opioid use disorder.
AB - BACKGROUND: Alcohol use among individuals with opioid use disorder (OUD) can be
dangerous, and understanding factors contributing to alcohol use in this
population is important. The current study examined alcohol use among individuals
with prescription OUD based on distress tolerance. It was hypothesized that
individuals with greater distress tolerance abilities would have a lower
frequency and quantity of alcohol use compared to individuals with less distress
tolerance. It was also hypothesized that this association would differ based on
gender. METHODS: A total of 122 individuals with prescription OUD participated in
the current study. Participants completed questionnaires regarding demographics,
distress tolerance, mental health symptoms, and frequency and quantity of alcohol
in the past 30 days. A regression model was conducted using the alcohol-related
variables as outcomes. RESULTS: There was a significant interaction between
gender and distress tolerance on alcohol use frequency. Greater distress
tolerance was associated with fewer alcohol use days in women, but there was no
association between distress tolerance and alcohol use days in men. CONCLUSIONS:
The findings suggest that distress tolerance skills may be key to reducing
alcohol use in women with prescription OUD.
PMID- 29960921
TI - Maternal immunization with a recombinant adenovirus-expressing fusion protein
protects neonatal cotton rats from respiratory syncytia virus infection by
transferring antibodies via breast milk and placenta.
AB - We evaluated the efficacy of a recombinant adenovirus that expresses a membrane
truncated respiratory syncytial virus (RSV) fusion protein (Ad-F0DeltaTM) in
newborns via maternal immunization (MI) of pregnant cotton rats. Intranasal Ad
F0DeltaTM immunization was given to pregnant female rats, and MI-newborn rats
were then challenged intranasally with RSV. Anti-RSV IgGs were observed in the
serum of MI-newborn rats after birth. The pulmonary viral loads in Ad-F0DeltaTM
vs. control vector, Ad-LacZ, and MI-newborns on day 3 post-challenge were reduced
by 4 log10/g lung. The neutralizing antibody remained for up to 3 weeks in the
serum of MI-newborns, which is when weaning began. Ad-F0DeltaTM protected MI
newborns from RSV challenge for 1 week. Vertical-transferred protective
antibodies were examined in the breast milk and placenta as well. Finally, anti
RSV immunity was not boosted but was only primed during the next RSV exposure in
Ad-F0DeltaTM-MI-newborns. Maternal Ad-F0DeltaTM immunization provides acute
protection against RSV infection in neonates.
PMID- 29960922
TI - Molecular evolution of fibropapilloma-associated herpesviruses infecting juvenile
green and loggerhead sea turtles.
AB - Chelonid Alphaherpesvirus 5 (ChHV5) has long been associated with
fibropapillomatosis (FP) tumor disease in marine turtles. Presenting primarily in
juvenile animals, FP results in fibromas of the skin, connective tissue, and
internal organs, which may indirectly affect fitness by obstructing normal turtle
processes. ChHV5 is near-universally present in tumorous tissues taken from
affected animals, often at very high concentrations. However, there is also
considerable asymptomatic carriage amongst healthy marine turtles, suggesting
that asymptomatic hosts play an important role in disease ecology. Currently,
there is a paucity of studies investigating variation in viral genetics between
diseased and asymptomatic hosts, which could potentially explain why only some
ChHV5 infections lead to tumor formation. Here, we generated a database
containing DNA from over 400 tissue samples taken from green and loggerhead
marine turtles, including multiple tissue types, a twenty year time span, and
both diseased and asymptomatic animals. We used two molecular detection
techniques, quantitative (q)PCR and nested PCR, to characterize the presence and
genetic lineage of ChHV5 in each sample. We found that nested PCR across multiple
loci out-performed qPCR and is a more powerful technique for determining
infection status. Phylogenetic reconstruction of three viral loci from all ChHV5
positive samples indicated widespread panmixia of viral lineages, with samples
taken across decades, species, disease states, and tissues all falling within the
same evolutionary lineages. Haplotype networks produced similar results in that
viral haplotypes were shared across species, tissue types and disease states with
no evidence that viral lineages associated significantly with disease dynamics.
Additionally, tests of selection on viral gene trees indicated signals of
selection dividing major clades, though this selection did not divide sample
categories. Based on these data, neither the presence of ChHV5 infection nor
neutral genetic divergence between viral lineages infecting a juvenile marine
turtle is sufficient to explain the development of FP within an individual.
PMID- 29960919
TI - Normal glutathione levels in autopsied brain of chronic users of heroin and of
cocaine.
AB - BACKGROUND: Animal studies suggest that exposure to either of the two widely used
drugs of abuse, heroin or cocaine, causes depletion of the antioxidant, reduced
glutathione, a hallmark of oxidative stress, in the brain. However, the relevance
of the animal findings to the human is uncertain and clinical trials with the
antioxidant GSH precursor n-acetylcysteine have produced mixed results in cocaine
dependence. METHODS: Our major objective was to compare glutathione levels,
determined by an HPLC-coulometric procedure, in autopsied brain of chronic heroin
(n = 11) and cocaine users (n = 9), who were positive for the drugs in the brain,
to those of matched controls (n = 16). Six brain regions were examined, including
caudate, hippocampus, thalamus and frontal, temporal and insular cortices.
RESULTS: In contrast to experimental animal findings, we found no statistically
significant difference between mean levels of reduced or oxidized glutathione in
the drug user vs. control groups. Moreover, no correlation was found between
levels of drugs in the brain and those of glutathione. CONCLUSIONS: Acknowledging
the many generic limitations of an autopsied human brain study and the
preliminary nature of the findings, our data nevertheless suggest that any
oxidative stress caused by heroin or cocaine in chronic users of the drugs might
not be sufficient to cause substantial loss of stores of glutathione in the human
brain, at least during early withdrawal. These findings, requiring replication,
might also have some relevance to future clinical trials employing glutathione
supplement therapy as an anti-oxidative strategy in chronic users of the two
abused drugs.
PMID- 29960923
TI - The role of ancillary ligand substituents in the biological activity of
triruthenium-NO complexes.
AB - Two novel triruthenium clusters, [Ru3(MU3-O)(MU-OOCCH3)6(NO)L2]PF6 (L = 4
acetylpyridine, 1, or 4-tert-butylpyridine, 2) release NO. Their spectroscopic
and electrochemical characterization confirmed their structure. These complexes
efficiently deliver NO in solution under irradiation at lambdairrad = 377 nm
and/or through chemical reduction with ascorbic acid. Clusters 1 and 2 elicit
vasodilation and, at concentrations of 10-5 M, can relax up to 100% of pre
contracted rat aorta. Complex 2 is more cytotoxic to murine melanoma B16F10 cells
than complex 1: at 50 times lower concentration than complex 1, complex 2
decreases cell viability to 50% in the dark or under irradiation with visible
light (lambdairrad = 527 nm). The higher cytotoxicity of complex 2 can be
assigned to its larger hydrophobicity, promoted by the methylated tert
butylpyridine ancillary ligand in its structure. Investigation into human serum
albumin (HSA) fluorescence quenching by clusters 1 or 2 revealed that complex 2
quenches HSA luminescence with a very high Stern-Vomer constant (KSV = 9.49 * 107
M-1 at T = 298 K) and suggested that the nature of the interaction between
complex 2 and HSA is hydrophobic (DeltaH = 80.81 kJ/mol and DeltaS = 334.71 J/K
mol). HSA lifetime and circular dichroism data pointed to a static quenching
mechanism for both complexes. Together, our results show that a hydrophobic
substituent in the cluster ancillary ligand improves NO release ability,
cytotoxicity, and interaction with a bio-target.
PMID- 29960924
TI - Silver pyridine-2-sulfonate complex - its characterization, DNA binding,
topoisomerase I inhibition, antimicrobial and anticancer response.
AB - In the current study the ability of silver pyridine-2-sulfonate complex to exert
multiple biological activities is compared with the pharmacological action of
silver sulfadiazine (AgSD). Polymeric form of {[Ag(py-2-SO3)]}n (AgPS) was
synthesized and characterized by analytical techniques (IR, CHN, TG/DTA, MS) and
its molecular formula was established. The crystal structure was determined by X
ray diffraction method and the polymeric complex crystallizes in the triclinic P
1 space group. The stability of Ag(I) complex was verified by 1H and 13C NMR
measurements and the interaction with calf thymus DNA through UV-VIS and
fluorescence quenching experiments was studied. The Ag(I) complex was able to
interact with DNA by dual binding mode: partial intercalation along groove
binding. The binding constants were calculated to be in the order of 103 M-1.
Topoisomerase I inhibition study have shown that silver complex is inhibiting its
activity at concentration of 30 MUM. The cytotoxic activity of AgPS and AgSD
against mouse leukaemia L1210 S, R and T cell line was also evaluated. AgPS
showed higher cytotoxicity than AgSD after 48 h incubation. The results suggest
that mechanism of cell death is necrosis with a contribution of late apoptosis.
Antimicrobial testing indicates higher growth inhibition effect of AgPS with
comparison to commercially available AgSD.
PMID- 29960925
TI - Consultation frequency in general practice before cancer diagnosis in relation to
the patient's usual consultation pattern: A population-based study.
AB - BACKGROUND: Cancer patients who usually consult the general practitioner (GP)
rarely are generally diagnosed with more advanced stages of cancer. This subgroup
of cancer patients may thus postpone relevant healthcare seeking. AIM: We aimed
to investigate the rates of daytime face-to-face consultations in general
practice before a cancer diagnosis in patients with different categories of
'usual' consultation frequency. MATERIAL AND METHODS: We conducted a population
based comparative study using register data on all 123,934 first-time cancer
patients aged 50-90 years who were diagnosed in 2009-2013 in Denmark. Usual
consultation rates were based on number of consultations from 19 to 36 months
before cancer diagnosis. We predicted the marginal monthly consultation rates for
up to 18 months before diagnosis. These were based on the estimated (mean) rates
of consultations with corresponding 95% confidence intervals (CIs), which were
calculated by negative binomial regression analysis with robust variance
estimation. RESULTS: Patients with cancer began to increase their consultation
frequency four to six months before their cancer diagnosis. The average monthly
consultation rates varied slightly across usual consultation groups; rates were
lowest among male 'frequent' consulters (0.28 (95% CI: 0.27;0.29)) and highest
among female 'frequent' consulters (0.35 (95% CI: 0.34;0.37)). The additional
number of consultations was 1-2 for all combinations of usual consultation
frequency, sex, and cancer type (except for female breast cancer and 'average'
consulters with lung or prostate cancer). CONCLUSION: Patients with cancer begin
to increase their consultation frequency in general practice before a cancer
diagnosis independently of their usual consultation frequency.
PMID- 29960926
TI - Subcellular distributions of trace elements (Cd, Pb, As, Hg, Se) in the livers of
Alaskan yelloweye rockfish (Sebastes ruberrimus).
AB - Yelloweye rockfish (Sebastes ruberrimus) is an extremely long-lived species (up
to ~120 years) of fish, which inhabits the coastal waters of Alaska. Due to their
long lifespans, yelloweye are known to accumulate high levels of mercury, and
potentially other trace elements, in their tissues. Relatively little is known
about the subcellular distribution of trace elements in the tissues of yelloweye
rockfish; such information can provide important insights into
detoxification/toxicity mechanisms at the subcellular level. To address this, we
collected yelloweye rockfish (n = 8) from the eastern coast of Prince of Wales
Island, Alaska in 2014. We determined the subcellular partitioning of trace
elements (cadmium (Cd), lead (Pb), arsenic (As), total mercury (Hg), and selenium
(Se)) in yelloweye livers with a partitioning procedure designed to separate
liver cells into putative metal-sensitive fractions (cytosolic enzymes,
organelles) and detoxified metal fractions (metallothionein or metallothionein
like proteins and peptides, granule-like structures) using differential
centrifugation, NaOH digestion, and heat denaturation steps. The resulting
fractions were then analyzed for total Hg with a direct Hg analyzer and for trace
element concentrations by inductively coupled plasma-mass spectrometry (ICP-MS).
For Cd, Pb, and As, the greatest contributions were found in the detoxified
fractions, whereas the majority of total Hg was found in sensitive fractions.
Selenium, an essential trace element, was distributed to a similar degree between
the sensitive and detoxified compartments. Results indicate that although
yelloweye sequestered and immobilized potentially toxic elements in detoxified
fractions, the extent of binding differed among elements and followed the order:
Cd > As > Pb > Hg. In yelloweye rockfish livers, the accumulation of non
essential elements at sensitive sites could lead to deleterious effects at the
subcellular level, which should be evaluated in future studies.
PMID- 29960927
TI - Removal of selenium containing algae by the bivalve Sinanodonta woodiana and the
potential risk to human health.
AB - Selenium (Se) is an essential micronutrient for animals and humans with a
relatively narrow margin between nutritional essentiality and potential toxicity.
Even though our previous studies have demonstrated algae could efficiently remove
Se, mainly through volatilization, concern is raised about eco-risks posed by the
remaining Se in algae. Here, Sinanodonta woodiana was investigated as a biofilter
for the removal of Se-containing Chlorella vulgaris and for its potential risk to
human health. Our results suggest filtration rates of S. woodiana were
independent of Se levels in algal biomass, with a removal efficiency of between
60 and 78%. However, Se concentrations accumulated in mussels were significantly
correlated with algal-borne Se levels, with a dietary assimilation efficiency
ranging from 12% to 46%. Thus, a pilot biofiltration system was set up to assess
uptake and depuration processes. The system was found to efficiently remove Se
laden algae through the uptake by mussels, while 21% of Se in mussels could be
depurated in 6 days. Among tissues, gills accumulated the highest Se
concentration after assimilating algal-borne Se but shed Se compounds in the
fastest pace during depuration. Health risks posed by consumption of mussels
exposed to different sources of Se were further assessed. S. woodiana accumulated
the highest Se concentration after exposure to waterborne SeMet, followed by
dietary Se, selenite and control. The relatively higher Se levels were found in
gills for all the treatments. After boiling, the most common method of cooking
mussels, the greatest reduction in Se concentration occurred in mantle for the
control and dietary Se groups and in muscle for the SeMet and selenite
treatments. Therefore, within the safe limits, Se-containing mussels can be
consumed as a dietary supplement. Overall, our research suggests incorporation of
mussels into an algal treatment system can improve Se removal efficiency and also
provide financial incentives for practitioners.
PMID- 29960928
TI - The impacts of nitrogen deposition on community N:P stoichiometry do not depend
on phosphorus availability in a temperate meadow steppe.
AB - Nitrogen (N) enrichment has great consequences on several fundamental ecological
processes through its impacts on plant nutrition traits (i.e. nutrient
concentration and stoichiometric ratios); however, the extent to which the
effects of N enrichment depend on phosphorus (P) availability are less well
understood. While there is mounting evidence for the species-specific responses
of plant nutrition traits to nutrient enrichment, we know little about the
changes at the community-level. Here, we measured community-level biomass
weighted (CWM) and non-weighted (CM) plant N and P concentrations and N:P ratio
in a temperate meadow steppe after four years factorial N and P addition, with
biomass and nutrition traits of each species in each plot being recorded.
Nitrogen addition significantly increased community-level N concentration,
decreased P concentration, and enhanced community N:P ratio. Phosphorus addition
had no impacts on community-level N concentration, significantly increased P
concentration, and reduced community N:P ratio. The impacts of N addition on
community nutrition traits were not dependent on P addition and the community
level nutrition trait responses to N and P additions were primarily driven by
intraspecific trait variation (ITV) rather than by species turnover. Community
level nutrition traits in the temperate meadow steppe were sensitive to the
projected N and P enrichment. While nutrient enrichment had substantially changed
community composition, its impacts on community nutrition traits were driven by
ITV. Nitrogen deposition would result in imbalance of N and P in plant community,
as indicated by the substantial increase in community-level N:P, which was not
affected by increased P availability.
PMID- 29960930
TI - The Little-known Freshwater Metopid Ciliate, Idiometopus turbo (Dragesco and
Dragesco-Kerneis, 1986) nov. gen., nov. comb., Originally Discovered in Africa,
Found on the Micronesian Island of Guam.
AB - Class Armophorea Lynn, 2004 includes two orders of mainly free-living anaerobic
ciliates, Armophorida Jankowski, 1980 and Metopida Jankowski, 1980 and, a third,
the exclusively endosymbiotic Clevelandellida. Kahl described the majority of
free-living metopid species early in the 20th century. Excepting Jankowski in the
1960's, little further interest was shown in this group. Metopus turbo Dragesco
and Dragesco-Kerneis, 1986, from a West African pond, was more recently
described. Although not explicitly described as endemic, Dragesco believed in
some degree of endemism of sub-Saharan ciliates. Our discovery of M. turbo on
Guam, Micronesia was unexpected. Metopus turbo was identified by live
observation, protargol impregnation, and scanning electron microscopy, providing
reasonable evidence of conspecificity when compared with the original
description. Outstanding morphologic features include the stout shape and
transversely situated bandform macronucleus. The morphology of Metopus turbo
differs markedly from that of the Metopus/Brachonella clade and is distant from
Metopus es in phylogenetic analyses. The 18S rDNA sequence of the Guam M. turbo
differs from that of M. es, type species of Metopus, by >8% and shows distinct
morphologic differences from the genus Atopospira to which it is sister. These
facts suggest that transfer to a new genus, Idiometopus gen. nov. is indicated.
PMID- 29960929
TI - Emission of sulfur dioxide from polyurethane foam and respiratory health effects.
AB - Recently, health damage to children exposed to synthetic polyurethane (PU)
running tracks has aroused social panic in China. Some possible toxic volatiles
may be responsible for these damages. However, the exact cause remains unclear.
We have detected a low concentration of sulfur dioxide (SO2; 1.80-3.30 mg/m3) on
the surface of the PU running track. Surprisingly, we found that SO2 was
generated from the PU running track, and even such a low concentration of SO2
could induce severe lung inflammation with hemorrhage, inflammatory cell
infiltration, and inflammatory factor secretion in mice after 2-week exposure.
Prolonged exposure (5 weeks) to the SO2 caused chronic pulmonary inflammation and
pulmonary fibrosis in the mice. Peripheral hemogram results showed that platelet
concentration increased significantly in the SO2 group compared to that in the
control group, and the proportion of blood neutrophils and monocytes among total
leukocytes was more imbalanced in the SO2 group (16.6%) than in the control group
(8.0%). Further histopathology results of sternal marrow demonstrated that
hematopoietic hyperplasia was severely suppressed with increased reticular stroma
and adipocytes under SO2 exposure. These data indicate that a low concentration
of SO2 generated spontaneously from PU running track outdoors as a secondary
product is still harmful to health, as it impairs the respiratory system,
hematopoiesis, and immunologic function. This indicates that the low
concentration SO2 could be a major cause of diseases induced by air pollution,
such as chronic obstructive pulmonary disease.
PMID- 29960931
TI - Calcineurin Silencing in Dictyostelium discoideum Leads to Cellular Alterations
Affecting Mitochondria, Gene Expression, and Oxidative Stress Response.
AB - Calcineurin is involved in development and cell differentiation of the social
amoeba Dictyostelium discoideum. However, since knockouts of the calcineurin
encoding genes are not possible in D. discoideum it is assumed that the
phosphatase also plays a crucial role during vegetative growth of the amoebae.
Therefore, we investigated the role of calcineurin during vegetative growth in D.
discoideum. RNAi-silenced calcineurin mutants showed cellular alterations with an
abnormal morphology of mitochondria and had increased content of mitochondrial
DNA (mtDNA). In contrast, mitochondria showed no substantial functional
impairment. Calcineurin-silencing led to altered expression of calcium-regulated
genes as well as mitochondrially-encoded genes. Furthermore, genes related to
oxidative stress were higher expressed in the mutants, which correlated to an
increased resistance towards reactive oxygen species (ROS). Most of the changes
observed during vegetative growth were not seen after starvation of the
calcineurin mutants. We show that impairment of calcineurin led to many subtle,
but in the sum crucial cellular alterations in vegetative D. discoideum cells. As
these alterations were not observed after starvation we propose a dual role for
calcineurin during growth and development. Our results imply that calcineurin is
one player in the mutual interplay between mitochondria and ROS during vegetative
growth.
PMID- 29960932
TI - Occurrence and persistence of carbapenemases genes in hospital and wastewater
treatment plants and propagation in the receiving river.
AB - This study aims to investigate the prevalence of clinically relevant
carbapenemases genes (blaKPC, blaNDM and blaOXA-48) in water samples collected
over one-year period from hospital (H), raw and treated wastewater of two
wastewater treatment plants (WWTPs) as well as along the Zenne River (Belgium).
The genes were quantified in both particle-attached (PAB) and free-living (FLB)
bacteria. Our results showed that absolute abundances were the highest in H
waters. Although absolute abundances were significantly reduced in WWTP
effluents, the relative abundance (normalized per 16S rRNA) was never lowered
through wastewater treatment. Particularly, for the PAB the relative abundances
were significantly higher in the effluents respect to the influents of both WWTPs
for all the genes. The absolute abundances along the Zenne River increased from
upstream to downstream, peaking after the release of WWTPs effluents, in both
fractions. Our results demonstrated that blaKPC, blaNDM and blaOXA-48 are widely
distributed in the Zenne as a consequence of chronic discharge from WWTPs. To
conclude, the levels of carbapenemases genes are significantly lower than other
genes conferring resistance to more widely used antibiotics (analyzed in previous
studies carried out at the same sites), but could raise up to the levels of high
prevalent resistance genes.
PMID- 29960933
TI - Mesoporous TiO2 with WO3 functioning as dopant and light-sensitizer: A highly
efficient photocatalyst for degradation of organic compound.
AB - The suitable doping or modification on TiO2 holds promise for improving charge
separation and extending light absorption range. Here, WO3 modifying reduced band
gap mesoporous TiO2 (WO3/RM-TiO2) due to WO3 doping was successfully fabricated
by immersing mesoporous TiO2 nanoparticles in the peroxotungstic acid sol with
controllable reaction time (0-1 h). The W6+ ions were first incorporated into the
TiO2 lattice to form WOTi bonds, resulting in the formation of WO3 doping TiO2.
Then, WO3 nanoparticles gradually formed and attached on the TiO2 surface,
constructing a novel heterojunction catalyst with WO3 serving as both dopant and
light-sensitizer for TiO2. Photocatalytic activity of the resulting WO3/RM-TiO2
depends on the immersing duration in the peroxotungstic acid. The BET analysis
shows that 0.5 h-WO3/RM-TiO2 has the largest pore volume of 0.491 cm3 g-1 and the
highest surface area of 82.3 m2 g-1, whereas these values decline with prolonged
immersing duration. As expected, the optimal efficiency in removing p-nitrophenol
(PNP) is achieved over 0.5 h-WO3/RM-TiO2 under visible light irradiation, which
is 2.33 times that of the unmodified M-TiO2. This should be attributed to the
suitable WO3 doping and WO3 modification.
PMID- 29960934
TI - Oxidation of Rhodamine B by persulfate activated with porous carbon aerogel
through a non-radical mechanism.
AB - In this study, porous carbon aerogel (CA) was synthesized with D-glucose,
ammonium persulfate and aniline by a hydrothermal carbonization method. It was
reported for the first time as an excellent catalyst for activating persulfate
(PS) to degrade rhodamine B (RhB). The morphology of CA was characterized,
exhibiting microporous and mesoporous structures. The solution pH of 3, 5, 7 and
9 showed slight impact on the degradation of RhB; however, when the pH increased
to 11, the removal of RhB decreased. The PS concentration and CA dosage played a
key role in the RhB degradation, and the activation energy was calculated to be
22.11 kJ/mol. Electron paramagnetic resonance (EPR) spectra suggested that
neither sulfate radical (SO4-) nor hydroxyl radical (OH) was generated from the
PS activation. The radical quenching experiments also confirmed that CA activated
PS in a non-radical pathway. It was indicated that PS bonded with CC in the sp2
hybridized system could directly degrade RhB. The defective edges at the boundary
of CA also facilitated the RhB removal. This work presented a green material with
both excellent catalytic performance and high regeneration possibility in the
heterogeneous metal-free PS activation, providing a new strategy in water
treatment.
PMID- 29960935
TI - Boron- and phenyl-codoped graphitic carbon nitride with greatly enhanced light
responsive range for photocatalytic disinfection.
AB - The development of metal-free photocatalyst to make maximum use of the solar
energy for photocatalytic disinfection is highly desired. Herein, boron-and
phenyl-codoped graphitic carbon nitride was prepared by thermal polycondensation
of cyanamide with 3-aminobenzeneboronic acid and applied as photocatalyst to
inactivate Escherichia coli (E. coli). The photocatalysts exhibited the enhanced
light responsive range over ultraviolet to near infrared light and 99.9% bacteria
could be inactivated within 3 h with a low concentration of photocatalyst under
the irradiation of simulated solar light. The disinfection mechanism was studied
by scavenger experiments, indicating H2O2 was the main reactive species for the
inactivation of bacteria. Finally, the photocatalyst was deposited on the surface
of solid material and also exhibited strong disinfection performance. Taking
advantage of excellent disinfection activity and low cytotoxicity, the
photocatalyst showed a promising application in solar-driven photocatalytic
disinfection in public place.
PMID- 29960936
TI - Innovative application for bauxite residue: Red mud-based inorganic polymer
spheres as pH regulators.
AB - In this study, and for the first time, red mud (RM)-based geopolymer spheres were
synthesised, with varying porosity and RM content, and then their use as pH
regulators was evaluated. The aluminosilicate sources of these inorganic polymers
were 100% waste-based, consisting of a mixture of RM and fly ash wastes.
Geopolymer spheres containing up to 60 wt.% RM were successfully produced, while
higher RM contents distorted the specimens' spherical shape. Results showed that
alkalis leaching from the spheres over time can be controlled by their porosity,
while the RM content induces only minor changes to leaching. The RM-based spheres
leached up to 0.0237 mol/dm3g of OH- ions from their structure, this being among
the highest values ever reported for geopolymers. This allowed a continuous and
prolonged pH buffer capacity with narrow pH decay over the 28 days (2.4 pH
units), suggesting the use of the RM-based spheres as pH buffering materials in
wastewater treatment and anaerobic digestion systems.
PMID- 29960937
TI - Distress tolerance as a mechanism of PTSD symptom change: Evidence for mediation
in a treatment-seeking sample.
AB - Low distress tolerance, the perceived or actual inability to tolerate negative
emotional states, is a transdiagnostic risk marker associated with greater PTSD
symptoms and poorer treatment outcomes. However, the role of distress tolerance
in PTSD symptom trajectories has not yet been explored. This study examined the
mediating role of distress tolerance in PTSD symptom change among outpatients
participating in a trial of computerized interventions for anxiety-related and
mood-related risk factors. It was hypothesized that pre- to post-intervention
change in distress tolerance would predict PTSD symptoms at three- and six-month
follow-up, and mediate the effect of condition on PTSD symptoms above and beyond
the effects of a competing mediator, anxiety sensitivity. Although condition
differences in distress tolerance change were non-significant, distress tolerance
change predicted month-three PTSD symptoms and mediated the direct effect of
condition on month-three PTSD symptoms. After accounting for the direct effect of
condition on month-six PTSD symptoms, distress tolerance change did not predict
month-six PTSD symptoms. Findings suggest distress tolerance does play a
longitudinal role in PTSD symptom change, and distress tolerance interventions
may benefit certain samples who may otherwise not be able to immediately access,
or remain in PTSD treatments.
PMID- 29960938
TI - Prevalence of psychological distress and the effects of resilience and perceived
social support among Chinese college students: Does gender make a difference?
AB - This study aimed to examine the gender differences in the prevalence of
psychological distress, and in the effects of resilience and perceived social
support on psychological distress among Chinese college students. A cross
sectional survey was conducted in current study. The psychological distress,
resilience, and perceived social support of 1400 university students of China
were measured using the Kessler Psychological Distress Scale, the 10-item Connor
Davidson Resilience Scale, and the 12-item Multidimensional Scale of Perceived
Social Support, respectively. Multiple group analyses were conducted using
structural equation modeling to examine the moderating role of gender in the
effects of resilience and perceived social support on psychological distress. The
prevalence of psychological distress was 90.86%. Female college students reported
a higher prevalence of psychological distress (94.07%) than males (89.11%). Among
male college students, the resilience was more strongly associated with
psychological distress than perceived social support (-0.18 vs.-0.16). In
contrast, among female college students, resilience was not significantly
related, but perceived social support was closely related with psychological
distress (0.01 vs. -0.31). In conclusion, Chinese female college students are
more vulnerable to psychological distress than males. Gender moderates the
relationships among resilience, perceived social support, and psychological
distress.
PMID- 29960939
TI - Individuals with Borderline Personality Disorder manifest cognitive biases
implicated in psychosis.
AB - Individuals with Borderline Personality Disorder (BPD) frequently manifest
psychotic symptoms. Certain cognitive biases have been implicated in the genesis
and maintenance of psychotic symptoms. The present study aimed at exploring
whether individuals with BPD manifest these cognitive biases. Twenty-eight
individuals with BPD and 28 healthy participants were assessed on four sub
domains of the Davos Assessment of Cognitive Biases Scale, viz. jumping to
conclusions, belief inflexibility, attention for threat and external attribution.
The BPD group had significantly higher scores on all the four cognitive biases in
comparison to the healthy controls. Thus, the findings of the present study
indicate that individuals with BPD manifest cognitive biases implicated in
psychosis more prominently than healthy individuals. These findings can be used
to improve the existing psychotherapeutic techniques for BPD.
PMID- 29960940
TI - Temporal and spatial distribution of Microcystis biomass and genotype in bloom
areas of Lake Taihu.
AB - Cyanobacterial blooms as a global environmental issue are of public health
concern. In this study, we investigated the spatial (10 sites) and temporal
(June, August and October) variations in: 1) their biomass based on chlorophyll-a
(chl-a) concentration, 2) their toxic genotype based on gene copy ratio of mcyJ
to cpcBA, and 3) their cpcBA genotype composition of Microcystis during
cyanobacterial bloom in Lake Taihu. While spatial-temporal variations were found
in chl-a and mcyJ/cpcBA ratio, only spatial variation was observed in cpcBA
genotype composition. Samples from northwestern part had a higher chl-a, but
mcyJ/cpcBA ratio didn't vary among the sites. High chl-a was observed in August,
while mcyJ/cpcBA ratio and genotypic richness increased with time. The spatial
variations in chl-a and mcyJ/cpcBA ratio and temporal variation in cpcBA genotype
were correlated negatively with dissolved N and positively with dissolved P.
Spatial distribution of Microcystis biomass was positively correlated with
nitrite and P excluding October, but no correlation was found for spatial
distribution of mcyJ/cpcBA ratio and cpcBA genotype. Spatial distribution of
toxic and cpcBA genotypes may result from horizontal transport of Microcystis
colonies, while spatial variation in Microcystis biomass was probably controlled
by both nutrient-mediated growth and horizontal transport of Microcystis. The
temporal variation in Microcystis biomass, toxic genotype and cpcBA genotype
composition were related to nutrient levels, but cause-and-effect relationships
require further study.
PMID- 29960941
TI - Anodic potentials, electricity generation and bacterial community as affected by
plant roots in sediment microbial fuel cell: Effects of anode locations.
AB - A planted sediment microbial fuel cell (PSMFC) is a promising new technology for
harvesting energy and remediating a contaminated geo-environment. In this study,
the effects of roots (of Acorus tatarinowii) on oxygen profiles in sediment,
power generation, and anodic bacterial community were investigated in PSMFCs and
unplanted SMFCs with different anode locations to roots. The presence of plant
did not improve the electricity generation when roots were placed on the surface
of an anode because a high amount of oxygen loss from roots increased the redox
potential at anode and made aerobic bacteria co-exit and compete with
electrochemically active bacteria in substance utilization. It was suggested to
place the anode under the roots with a proper distance, where the PSMFCs made use
of root-derived organics, avoiding the negative effects of oxygen loss. Oxygen
loss could control the diurnal rhythm of power generation in the PSMFCs.
PMID- 29960942
TI - Impact of interaction between Limnoperna fortunei and Roundup Max(r) on
freshwater phytoplankton: An in situ approach in Salto Grande reservoir
(Argentina).
AB - The joint impact of the glyphosate-based commercial formulation Roundup Max(r)
and the invasive mussel Limnoperna fortunei on phytoplankton and water quality
was assessed in Salto Grande reservoir, a scenario were both stressors coexist.
We performed an in situ mesocosm approach, through a 7-day experiment using 400-L
enclosures. The following treatments were applied by triplicate: addition of 250
mussels (M); addition of 5 mg L-1 of active ingredient (a.i.) in Roundup Max(r)
(R); addition of 250 mussels and 5 mg L-1 of a.i. in Roundup Max(r) (MR), and
controls, without any addition (C). R showed higher total phosphorus (TP) and
ammonium nitrogen (NNH4+) concentrations due to the herbicide input, and a
significant increase in algal abundance, biovolume and chlorophyll a levels (Chl
a). In M mussels grazed on phytoplankton, which resulted in subsequent phosphates
(SRP) release. A decrease in species diversity was observed in R and M with
respect to C. In MR, there were higher TP and NNH4+ concentrations, a decrease in
biovolume, an antagonistic effect on Chl-a and a synergistic effect on
phytoplankton abundance. Species diversity and evenness showed a significant
decrease due to the explosive growth of a small and opportunistic Chlorophyta,
Spermatozopsis exsultans. The dominance of this species may be due to negative
selectivity for S. exsultans and/or release of potential competitors by L.
fortunei, and to the input of nutrients by Roundup Max(r) and/or removal of
competitors by its toxicity.
PMID- 29960943
TI - Typical polar organic aerosol tracers in PM2.5 over the North China Plain:
Spatial distribution, seasonal variations, contribution and sources.
AB - PM2.5 samples were collected simultaneously at three urban sites including
Beijing (BJ), Tianjin (TJ), Shijiazhuang (SJZ) and one background site Xinglong
(XL) from June 2014 till April 2015. Typical polar organic aerosol tracers
including 2-methylglyceric acid, 2-methyltetrols, 3-hydroxyglutaric acid,
anhydrous saccharides and phthalic acid were analyzed by gas chromatography-mass
spectrometry. Both Isoprene secondary organic aerosol (SOA) tracers and pinene
SOA tracers had higher mass concentrations at background site than those at urban
sites. But they showed different seasonal variations. The former had the highest
mass concentration in summer while the latter had the highest mass concentration
in spring. Anhydrous saccharides and phthalic acids at urban sites had higher
mass concentrations than those at background site and showed higher mass
concentration in autumn and winter, respectively. Corresponding estimated
secondary organic carbons (SOCs) showed similar variation trends with tracers. In
general, biogenic sources had more influence on background site while urban sites
were more affected by anthropogenic sources.
PMID- 29960944
TI - Attenuation of pharmaceuticals, nutrients and toxicity in a rural sewage lagoon
system integrated with a subsurface filtration technology.
AB - Although many studies have addressed the ability of subsurface filtration systems
to remove emerging contaminants from wastewater at micro- and mesocosm-scale,
little is known about their performance on full-scale wastewater treatment
facilities. To understand better how effective these systems can be for municipal
wastewater polishing, we assessed the ability of a full-scale lagoon-subsurface
filter system located in Dunnottar, Manitoba, Canada, to attenuate regulatory
wastewater parameters, nutrients, pharmaceuticals, and toxicity over the course
of the discharge periods in 2015 and 2016 (June-October). Pharmaceuticals
included beta-blockers, anticonvulsant drugs, and macrolide and sulfonamide
antibiotics. Out of six consistently detected pharmaceuticals, four were
efficiently removed through lagoon treatment (e.g. clarithromycin, metoprolol,
propranolol), while two persisted to a certain extent (e.g. carbamazepine,
sulfamethoxazole), even after subsurface filtration. Attenuation was observed for
nutrients with averages of 40% and 60% for ammonia and total phosphorus
respectively within the filter, consistent with previous pilot-scale studies at
this facility. Compliance with regulations for conventional wastewater parameters
at the effluent was observed, as well as reduced acute toxicity (as determined by
Microtox(r)) from the primary lagoon to the effluent, and little likelihood of
acute toxicity in receiving waters. Our results suggest that first, the full
scale system has an overall similar performance when compared to the previously
studied pilot-scale system; second, there was no apparent effect of acclimation
on the attenuation of studied contaminants or toxicity; and finally, the
concentrations of contaminants do not appear to pose an acute risk for aquatic
species in the receiving environment.
PMID- 29960945
TI - Effect of mixed chelators of EDTA, GLDA, and citric acid on bioavailability of
residual heavy metals in soils and soil properties.
AB - Soil washing is an effective technology for the remediation of multi-metal
contaminated soils. However, bioavailability of residual heavy metals in soils
and soil properties could be changed during washing processes. This study
investigated the effects of EDTA, FeCl3 and mixed chelators (MC) on
bioavailability of residual heavy metals in soils and soil biological properties
after soil washing. The results showed that soil washing by chelators
successfully decreased the total concentration of heavy metals in soils, while it
did not effectively decrease the exchangeable fraction of heavy metals,
especially for calcareous contaminated soil. The toxic effects of the washed
soils seemed to exhibit higher correlations with the changes in the soil
properties such as soil pH and nutrient concentrations. As compared with FeCl3
and EDTA, MC tended to moderately change soil properties (e.g., pH, total N,
available N, available P, and exchangeable K, Ca, and Mg). Additionally, MC
washed soil had the least influence on the soil enzymes activities, and had the
highest germination and growth of Chinese cabbage. Accordingly, MC is a moderate
washing solution in the removal of heavy metals from multi-metal contaminated
soils, and had minimal negative effects on soil qualities.
PMID- 29960946
TI - Water-stable metal-organic frameworks for aqueous removal of heavy metals and
radionuclides: A review.
AB - Heavy metals and radionuclides in water are a global environmental issue, which
has been receiving considerable attention worldwide. Water-stable MOFs are green
and recyclable materials to eliminate the environmental impacts caused by the
hazardous heavy metal ions and radionuclides in water. This paper presents a
systematical review on the current status of water-stable MOFs that capture and
convert a wide range of heavy metal ions (e.g., As(III)/As(V), Pb(II), Hg(II),
Cd(II), and Cr(III)/Cr(VI)) and radionuclides (e.g., U(VI), Se(IV)/Se(VI) and
Cs(I)) in aqueous solution. Water-stable MOFs and MOF-based composites exhibit
the superior adsorption capability for these metal species in water.
Significantly, MOFs show high selectivity in capturing target metal ions even in
the presence of multiple water constituents. Mechanisms involved in capturing
metal ions are described. MOFs also have excellent catalytic performance
(photocatalysis and catalytic reduction by formic acid) for Cr(VI) conversion to
Cr(III). Future research is suggested to provide insightful guidance to enhance
the performance of the MOFs in capturing target pollutants in aquatic
environment.
PMID- 29960948
TI - Investigation of some of the factors influencing fingermark detection.
AB - The primary aims of fingermark detection research are to improve the quality and
increase the rate of detection of identifiable impressions. This is usually
performed through the development of new methods and technologies to provide
alternatives to or improve current procedures. While research of this nature is
important to pursue, it fails to address the underlying question related to the
factors that affect the detection of a latent fingermark. There has been
significant research that has examined the differences between techniques, donors
and fingermark age, as well as the composition of latent fingermarks. However,
they tend not to focus on determining how these factors influence the quality of
the developed mark. This study involved the development and evaluation of over
14,000 natural fingermarks deposited on a variety of surfaces to examine the
effect of substrate, age, donor variability (both inter- and intra-), depletions
and type of finger on fingermark development. Fingermarks were deposited on four
substrates (two non-porous and two porous) and developed with either indanedione
zinc (IND-Zn) or cyanoacrylate followed by rhodamine 6G staining (CA+R6G). Three
independent assessors graded each mark on the quality of development using an
absolute scale proposed by the UK Centre for Applied Science and Technology
(CAST). The data generated from these assessments were then analysed for trends
or other useful insights. The results from this work reaffirm that individual
substrate characteristics (and the choice of development technique) play a
significant role in determining the number and quality of marks developed. It was
found that fingermarks were more likely to be detected on porous substrates and
to also be of a higher quality than on non-porous. The effect of fingermark donor
variability was also explored, with significant differences observed between
donors and within donors. This research shows that current detection techniques
do not detect all available fingermarks, reinforcing the need for further
research into the fundamentals of fingermark detection in order to gain a better
understanding of the techniques currently used. The study has identified
considerations for the development of novel techniques and how we need to account
for variability when designing fingermark research experiments.
PMID- 29960947
TI - Combined effects of antifouling biocides on the growth of three marine microalgal
species.
AB - The toxicity of the antifouling compounds diuron, irgarol, zinc pyrithione
(ZnPT), copper pyrithione (CuPT) and copper was tested on the three marine
microalgae Tisochrysis lutea, Skeletonema marinoi and Tetraselmis suecica.
Toxicity tests based on the inhibition of growth rate after 96-h exposure were
run using microplates. Chemical analyses were performed to validate the exposure
concentrations and the stability of the compounds under test conditions. Single
chemicals exhibited varying toxicity depending on the species, irgarol being the
most toxic chemical and Cu the least toxic. Selected binary mixtures were tested
and the resulting interactions were analyzed using two distinct concentration
response surface models: one using the concentration addition (CA) model as
reference and two deviating isobole models implemented in R software; the other
implementing concentration-response surface models in Excel(r), using both CA and
independent action (IA) models as reference and three deviating models. Most
mixtures of chemicals sharing the same mode of action (MoA) were correctly
predicted by the CA model. For mixtures of dissimilarly acting chemicals, neither
of the reference models provided better predictions than the other. Mixture of
ZnPT together with Cu induced a strong synergistic effect on T. suecica while
strong antagonism was observed on the two other species. The synergy was due to
the transchelation of ZnPT into CuPT in the presence of Cu, CuPT being 14-fold
more toxic than ZnPT for this species. The two modelling approaches are compared
and the differences observed among the interaction patterns resulting from the
mixtures are discussed.
PMID- 29960949
TI - Irinotecan delivery by unimolecular micelles composed of reduction-responsive
star-like polymeric prodrug with high drug loading for enhanced cancer therapy.
AB - Nanomedicine based polymeric prodrug have showed high impact in the inhibition of
tumor growth due to its high therapeutic efficiency and improved
biocompatibility. Herein, we synthesized a novel star-like amphiphilic copolymer
[beta-CD-P(Ir-co-OEGMA), denoted as CPIO] through atom transfer radical
polymerization (ATRP) to deliver the hydrophilic anticancer drug irinotecan (Ir).
The polymer could form monodisperse unimolecular micelles and had excellent
stability in aqueous solution. Moreover, the reduction-responsive feature of the
micelles facilitated controlled release of drug, thus achieving targeted therapy
and reduced toxicity to healthy cells. The in vitro cytotoxicity assays indicated
that CPIO had a notable anticancer effect against HeLa and MCF-7 tumor cells. The
confocal laser scanning microscopy and flow cytometry experiments revealed that
CPIO micelles could be internalized into tumor cells efficiently. Furthermore,
the obtained prodrug micelles produced better efficacy compared to free Ir.
Moreover, the CPIO micelles showed excellent biocompatibility in vivo after
intravenous injection on a mouse model. This study demonstrated that CPIO carrier
could provide a rational design of a stimuli-responsive polymeric prodrug for
delivery of irinotecan.
PMID- 29960950
TI - Three dimensional macroporous hydroxyapatite/chitosan foam-supported polymer
micelles for enhanced oral delivery of poorly soluble drugs.
AB - In the current study, a novel three-dimensional macroporous hydroxyapatite/
chitosan foam (HA/CS)-supported polymer micelle (PM/HA/CS) was developed, and its
potential as an oral drug delivery system to enhance the solubility and oral
bioavailability of poorly soluble compounds was systemically studied. Candesartan
cilexetil (CC) was selected as a poorly soluble model drug. Firstly, HA/CS foam
was synthesized using a wet chemical co-precipitation approach and poly-(methyl
methacrylate) colloidal crystals as a macropore template. Subsequently, the CC
loaded polymer micelles were efficiently encapsulated into the macropores of the
HA/CS foam and freeze-dried to produce powdery CC-loaded PM/HA/CS composites (CC
PM/HA/CS). The resulting CC-PM/HA/CS particles were then characterized in terms
of porous structure, morphology, angle of repose, crystallinity, drug loading,
dissolution profiles, and physical stability. Differential scanning calorimetry
(DSC) analysis confirmed that CC-PM/HA/CS was present in an amorphous form and
has an excellent physical stability. Under both simulated gastric and intestinal
conditions, the aqueous solubility and dissolution rate of the PM/HA/CS-based CC
formulation were significantly increased compared with the pure drug powder. In
addition, PM/HA/CS is almost completely non-cytotoxic. The PM/HA/CS-based CC
formulation produced approximately 1.9-fold increased bioavailability when
compared to the marketed tablets (Blopress(r)) administered to fasted Sprague
Dawley rats. On the whole, PM/HA/CS benefits from the advantages of three
dimensional macroporous HA/CS foam and polymer micelles, and exhibits great
potential as a drug delivery system for increasing the solubility and oral
bioavailability of a poorly soluble compound, like CC.
PMID- 29960951
TI - Promising effects of silver tungstate microcrystals on fibroblast human cells and
three dimensional collagen matrix models: A novel non-cytotoxic material to fight
oral disease.
AB - Silver tungstate (alpha-Ag2WO4) microcrystals have shown encouraging results
regarding their antimicrobial activity. However, in addition to the promising
outcomes in fighting oral disease, cytotoxic tests are mandatory for screening
new materials for biological applications. Here, we developed a better
understanding of the effects of microcrystals on the behavior of both human
gingival fibroblast (HGF) cells and three-dimensional (3D) collagen matrices. To
perform these experiments, the lowest concentration of alpha-Ag2WO4 capable of
preventing the visible growth of Candida albicans (C. albicans) planktonic cells
was defined as the test concentration, and it ranged from 0.781 (C1) to 7.81 (C2)
to 78.1 (C3) MUg/mL. Complete medium and lysis buffer (LB) served as negative (C
) and positive (C+) controls, respectively. The effect of the microcrystal
concentration on the morphology, remodeling and proliferation of HGF cells was
evaluated by different approaches. Quantitative and qualitative assessments
demonstrated that alpha-Ag2WO4 did not affect the mitochondrial enzymatic
activity of HGF cells cultured in a monolayer or the cell viability within 3D
collagen matrices. These experiments showed that alpha-Ag2WO4 at the C2
concentration did not damage the genomic DNA. The development of new materials is
attractive for the possible treatment of diseases and for avoiding indiscriminate
prescribing of antibiotics. These findings provide information on the effect of
alpha-Ag2WO4 on cell behavior and reveal that these microcrystals are non
cytotoxic against human gingival cells over a sufficient period to measure the
hazard potential.
PMID- 29960952
TI - pH sensitive liposomes delivering tariquidar and doxorubicin to overcome
multidrug resistance of resistant ovarian cancer cells.
AB - Multidrug resistance of tumour cells is one of the most important hurdles in
tumour chemotherapy. To overcome the multidrug resistance, we constructed a pH
sensitive liposome formulation (pHSL) by loading tariquidar (TQR) and DOX
simultaneously in this work. The formulation showed high stability at pH 7.4 and
excellent sensitivity at acidic pH, which facilitated the delivery of TQR and DOX
into cells. Cellular experiments demonstrated that the pHSL/TQR/DOX 0.05 could
almost restore the drug sensitivity of OVCAR8/ADR cells. Therefore, the pH
sensitive liposome formulation pHSL/TQR/DOX 0.05 was very promising in treating
resistant tumours.
PMID- 29960953
TI - Mast cells and basophils in allergic inflammation.
AB - Mast cells and basophils have similar characteristics in terms of their function
and development. They both have detrimental functions, being implicated in pro
inflammatory responses to allergens, but can also provide protection against
multicellular parasites such as parasitic worms (helminths). Both cell types
express the high affinity Fc receptor for IgE, FcepsilonRI, and allergen cross
linking of this receptor triggers degranulation and release a set of cytokines
and biochemical mediators. Although mast cells and basophils are similar in many
respects, newly developed antibody reagents and genetically modified mouse models
that enable cell type-specific deletion have allowed us to appreciate their
independent in vivo roles. This review focuses on recent advances in our
understanding of the contribution of basophils and mast cells to innate and
adaptive allergic responses.
PMID- 29960954
TI - Mortality among diagnostic medical radiation workers in South Korea, 1996-2015.
AB - OBJECTIVES: To evaluate the risk for all-cause and cause-specific mortality in
diagnostic medical radiation workers in South Korea. METHODS: The study
population included all diagnostic medical radiation workers enrolled in the
National Dosimetry Registry (NDR) between 1996 and 2011. NDR data were linked
with mortality data obtained from national registries through 2015. Standardised
mortality ratios (SMRs) and relative standardised mortality ratios (rSMRs) were
calculated for external comparison and for adjustment of the cohort's overall
healthiness. RESULTS: A total of 1099 deaths (974 in men and 125 in women) were
reported from among 80 837 medical radiation workers. The SMRs for all causes of
death were significantly lower than expected in both men (SMR 0.45, 95% CI 0.42
to 0.48) and women (SMR 0.49, 95% CI 0.41 to 0.58). No excesses were observed for
any specific cause of death. The findings were similar by job title, calendar
year of entry and year of birth. However, relative to all causes of death,
mortality from all cancers (rSMR 1.60, 95% CI 1.41 to 1.82), leukaemia, colon
cancer, stomach cancer and diseases of the circulatory system increased
significantly among male workers. The results for female workers were limited due
to small number of deaths; however, the rSMR for all cancers was significantly
elevated (rSMR 1.70, 95% CI 1.17 to 2.46). CONCLUSIONS: This cohort showed lower
mortality among diagnostic medical radiation workers than in the general
population. However, occupational factors may have been involved in the increased
relative mortality for several causes of death.
PMID- 29960955
TI - Correlates of disrupted sleep-wake variables in patients with advanced cancer.
AB - OBJECTIVES: High rates of sleep difficulties have been found in patients with
advanced cancer. However, not much is known about factors that are associated
with sleep impairments in this population and that could constitute their
potential risk factors or consequences. This study conducted in patients with
cancer receiving palliative care aimed to evaluate the relationships of
subjective (sleep diary; Insomnia Severity Index, ISI) and objective (actigraphy)
sleep-wake variables with several physical and psychological symptoms,
maladaptive sleep behaviours, erroneous beliefs about sleep, quality of life,
time to death and environmental factors. METHODS: The sample was composed of 57
community-dwelling patients with cancer receiving palliative care and with an
Eastern Cooperative Oncology Group Scale score of 2 or 3. Actigraphic, light and
sound recording and a daily sleep and pain diary were completed for seven
consecutive days. A battery of self-report scales was also administered. RESULTS:
Greater disruptions of subjective and objective sleep-wake variables were more
consistently associated with worse physical symptoms than with psychological
variables. Disrupted objective sleep-wake parameters were also associated with a
greater frequency of maladaptive sleep behaviours. Finally, a greater nocturnal
noise in the bedroom was correlated with more impairments in subjective and
objective sleep-wake variables while a lower 24-hour light exposure was
associated with more disruption of subjectively assessed sleep only. CONCLUSIONS:
Although longitudinal studies are needed to establish the etiology of sleep-wake
difficulties in patients with advanced cancer, our findings suggest that physical
symptoms, maladaptive sleep behaviours and environmental factors can contribute
to their development or their persistence and need to be adequately addressed.
PMID- 29960956
TI - Laparoscopic excision of round ligament endometrioma.
AB - A 14-year-old female patient consulted due to 4 months of recurrent right pelvic
pain during her menstrual period. Sonography revealed a 35 mm haemorrhagic right
ovarian cyst, initially treated with hormone therapy and oral analgesics with no
response. Surgery was indicated due to growth on sonography control and no
response to medical treatment. Laparoscopy showed a 7 cm leiomyomatous-like mass
arising from the right round ligament that was extracted en bloc without rupture
with right salpingectomy and ovarian preservation. The histopathological
examination confirmed the diagnosis of round ligament endometrioma with no
atypia. The patient presented an uncomplicated postoperative course and was
discharged home 48 hours after surgery. Hormonal contraceptives were initiated
after the histopathological confirmation; the patient remains asymptomatic at 1
year follow-up.
PMID- 29960957
TI - Phytobezoar and duodenal ulcer as complication of Duodopa therapy in a patient
affected by Parkinson's disease.
AB - Continuous duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an
established treatment to control motor fluctuations in Parkinson's disease.
Duodenal infusion allows a steady absorption of the drug in the small bowel,
reducing plasmatic fluctuations of levodopa. Some complications may occur during
the treatment, often related to intrajejunal percutaneous endoscopic gastrostomy
(PEG-J). We report a case of duodenal ulcer associated with a phytobezoar
involving the end of jejunal probe, in a patient who underwent PEG-J for LCIG
infusion. In the last 2 weeks, the patient suffered from abdominal pain and
dyspepsia. Oesophagogastroduodenoscopy showed an ulcerative lesion of the
duodenum due to traction of the jejunal tube; the end of the jejunal tube was
wrapped in a phytobezoar. This case is interesting because of the extension of
the ulcerative lesion due to PEG-J dislocation and because of the subtle symptoms
associated with it.
PMID- 29960958
TI - Ectopic insulinomas in the pelvis secondary to rectum neuroendocrine tumour.
AB - We describe a middle-aged woman with recurrent hypoglycaemia, who confirmed with
rectum G1 neuroendocrine tumour (NET) 6 years ago. Biochemical assay showed high
concentration of serum insulin and C-peptide associated with hypoglycaemia.
Because of recurrent hypoglycaemia in June 2015, she underwent a resection of the
tail of the pancreas. However, hypoglycaemia attack happened more frequently and
severely. 68Ga-DOTA-NOC positron emission tomography/CT revealed five foci in the
pelvis with intense uptake. Immediately after excision of the pelvic lesions,
insulin and C-peptide decreased to normal levels promptly, and therefore, serum
glucose increased significantly. Hypoglycaemia was disappeared, and insulin and C
peptide were normal at 2 years follow-up after surgery. Immunohistochemistry
validated the primary rectum NET and pelvic tumours expressed with higher
insulin, somatostatin receptor and glucagon-like peptide-1. This is the first
reported ectopic pelvic insulinomas secondary to rectum NET, which may originate
both from neuroendocrine cells in the rectum and pelvic tissues.
PMID- 29960959
TI - Unusual cause of elbow pain in a baseball pitcher.
AB - An adolescent, right hand-dominant, baseball pitcher presented to sports medicine
clinic with posterolateral right elbow pain over 4 months. He rated his pain as
8/10 with pitching, especially at the late cocking phase of throwing. Prior to
consult, he had rested 3 months from pitching, progressing to strengthening
exercises, with no pain relief. On physical examination, he had 120 degrees of
active external rotation, 80 degrees of active internal rotation, mild
tenderness to palpation over the capitellum and normal elbow radiography.
Magnetic resonance arthrogram of the right elbow revealed subtle, posterolateral
joint capsular tear and adjacent synovial hypertrophy. The patient was diagnosed
with elbow synovial fold syndrome that was causing impingement at the
radiocapitellar joint and was referred to an orthopaedic surgeon. Arthroscopy
revealed redundant tissue; scar formation at the radiocapitellar joint was
debrided. The patient participated in physical therapy for 2 months and was able
to start throwing 3 months later.
PMID- 29960960
TI - Early-stage right temporal lobe variant of frontotemporal dementia: 3 years of
follow-up observations.
AB - The right temporal lobe variant of frontotemporal dementia (FTD) is an uncommon
progressive neurodegenerative disorder. We present the case of a 77-year-old
right-handed man who presented with altered behaviour and problems with
interpersonal relationships. He had no decline in cognitive function but brain
perfusion single-photon emission CT demonstrated distinct hypoperfusion in the
right temporal pole. At 2-year follow-up, he could not recognise his wife's
relatives; and at 3-year follow-up, he had semantic aphasia. Decreased brain
perfusion extended from the right temporal lobe into the contralateral temporal
and both frontal lobes. These findings suggest that the right temporal lobe
variant of FTD should be considered in elderly patients with altered behaviour
and problems with interpersonal relationships, even if dementia is not suspected.
The right anterior temporal lobe may play a key role in the onset of the early
symptoms of this disease.
PMID- 29960961
TI - Suction-induced retinopathy: optical coherence tomography correlations.
AB - We report a clinical case of a teenager whose eyes were exposed to highly
negative suction pressures for brief seconds. The patient presented with a
bilateral cystoid macular oedema associated with a thickening of outer nuclear
layer evidenced by optical coherence tomography. The patient's constellation of
findings is most easily explained by the abrupt expansion and traction of a
cohesive vitreous base onto the retinal layers.
PMID- 29960962
TI - Second look at Streptococcus sanguinis and the colon.
AB - Although the link between Streptococcus bovis bacteraemia and colon cancer is
well established, bacteraemia from other viridans group streptococci that
commonly colonise colonic mucosa may also herald occult malignancy. We present a
case of Streptococcus sanguinis bacteraemia in an elderly man with new anaemia
that led to the detection and removal of a high-grade colon neoplasm. This case
contributes to a growing body of literature contending that unexplained
streptococcal bacteraemia merits a thorough workup that may include relatively
invasive procedures such as endoscopy. Diagnostic colonoscopy provides an
opportunity to prevent invasive malignancy that may outweigh bleeding and
perforation risks in elderly patients.
PMID- 29960963
TI - EBV colitis with ulcerative colitis: a double whammy.
AB - We report this case of a 21-year-old immunocompetent man presenting with
ulcerative colitis and superimposed Epstein-Barr virus (EBV) colitis. He
presented for the first time with symptoms of blood-mixed diarrhoea and raised
inflammatory markers. His endoscopic and histological appearances were found to
be due to ulcerative colitis for which he was started on standard therapy with
intravenous steroids. In spite of this, he continued to be symptomatic and his
inflammatory markers continued to rise. A virology screen done showed evidence of
previous EBV infection, and in view of poor response to immunosuppression, a
superimposed infection was suspected. EBV DNA PCR done on colonic biopsies was
found to be positive and the patient was started on intravenous ganciclovir to
which he responded well. This case highlights the importance of considering a
superimposed infection in patients with poor initial response to steroid therapy
in inflammatory bowel disease.
PMID- 29960965
TI - Pineal gland apoplexy mimicking as migraine-like headache.
PMID- 29960964
TI - Reversible cardiac dysfunction in long-standing hypertension may be global
variant of stress cardiomyopathy.
AB - An adult man with long-standing poorly controlled cardiac risk factors presented
with acute decompensated heart failure (ADHF). Echocardiogram, cardiac MRI and
catheterisation suggested idiopathic dilated cardiomyopathy, severe systolic
dysfunction, ejection fraction 25% with global left ventricular (LV) dilation and
apical thrombus. He responded well to diuretics and gradual uptitration of
lisinopril and carvedilol. Follow-up echocardiogram in 2 months demonstrated
complete recovery of systolic function, normalisation of LV size and shape with
severe LV hypertrophy. This presentation is potentially a global variant of
stress cardiomyopathy with recovery of LV function, highlighting the importance
of appropriate imaging, catheterisation and clinical monitoring in patients with
ADHF.
PMID- 29960966
TI - Inflammatory myofibroblastic tumour: a rare cause of central airway obstruction.
PMID- 29960967
TI - Just another case of bacterial meningitis... or... is it?
AB - Non-traumatic cerebrospinal fluid (CSF) rhinorrhoea is a rare condition. We
describe a case of a 62-year-old woman with pneumococcal bacterial meningitis who
later was found to have CSF rhinorrhoea secondary to an eroding skull base
tumour, which was proven to be pituitary macroadenoma on biopsy. She recovered
well from meningitis without any neurological sequelae and underwent trans
sphenoidal surgery for tumour removal as well as dural repair.
PMID- 29960968
TI - Atypical presentation of type B aortic dissection mimicking appendicitis managed
medically.
AB - This is a case of a 53-year-old male patient with a history of hypertension who
developed sudden onset of right lower quadrant pain. On arrival, chest X-ray
showed prominent aortic arch without cardiomegaly. CT of the abdomen/pelvis
showed aortic dissection in descending aorta without rupture. CT of the chest
displayed sparing of ascending and aortic arch. Ultrasound Doppler of the kidney
displayed mild renal artery stenosis. Differential diagnosis was acute
appendicitis, acute ureteric and severe gastroenteritis. The patient was started
on oral blood pressure (BP) medicine to titrate off intravenous nicardipine and
esmolol drip. After 10 days, he was switched to oral BP medicine. His leg pain
was resolved with normal palpable pulse. One week later, his kidney function
worsened. Thus, Lasix and minoxidil were stopped. The patient had no
chest/abdominal pain and was tolerating the medicine well during his 2-week
follow-up. Acute aortic dissection can be a fatal clinical emergency. Timing is
critical during diagnosis and management of patients.
PMID- 29960969
TI - Double tongue signs in a case of submandibular space infection.
PMID- 29960970
TI - Adult-onset epileptic aphasia.
AB - Aphasia is a language disorder characterised by loss of ability to produce or
comprehend written or spoken language. In majority of the cases, it is due to
stroke. Aphasia may also present as an ictal or postictal state of temporal or
frontal lobe seizures. Nevertheless, its isolated occurrence in individuals
without a clear-cut history of seizures raises diagnostic difficulties with
important therapeutic implications.A case of epileptic aphasia is reported in
which the diagnosis was confirmed by electroencephalogram with a dramatic
therapeutic response to an antiepileptic drug.
PMID- 29960971
TI - Ayurveda metallic-mineral 'Bhasma'-associated severe liver injury.
AB - Ayurveda Bhasma is a metallic-mineral preparation homogenised with herbal juices
or decoctions and modified with heat treatment to apparently detoxify the heavy
metals. It is widely recommended for the treatment of many disease conditions by
practitioners of complementary and alternative medicine in the absence of good
quality clinical trial evidence on its safety and efficacy. Heavy metal-induced
liver injury is widely reported in the literature, and heavy metal adulteration
of non-Bhasma-related Ayurveda and herbal products has been well described. We
report a patient who developed severe liver injury requiring listing for liver
transplantation for improved survival, after consumption of Bhasma for dyspepsia.
This case describes the first documented case and toxicology analysis of Ayurveda
Bhasma associated with severe drug-induced liver injury. Physicians must be alert
regarding patient's use of supposedly safe Ayurveda Bhasma that may promote acute
severe liver injury in the absence of other known aetiologies.
PMID- 29960972
TI - Anomalous aortic origin of a coronary artery with an intraseptal course: novel
techniques in haemodynamic assessment.
PMID- 29960973
TI - Pseudo-Wellens' syndrome secondary to concurrent cannabis and phencyclidine
intoxication.
AB - Wellens' syndrome is an electrocardiographic pattern of T-wave changes associated
with critical stenosis of the proximal left anterior descending artery,
signifying imminent risk of an anterior-wall myocardial infarction. The Wellens'
electrocardiographic pattern can also be noted in several cardiac and non-cardiac
diseases. We chronicle here a unique case of a patient who presented with
atypical left chest pain and dizziness for 6 hours. His pain started after he
smoked phencyclidine-laced cannabis. Cardiac panel demonstrated normal troponin T
levels. Electrocardiogram showed sinus rhythm with new deep biphasic T-wave
inversions in anterolateral leads. Coronary angiography showed no pathological
processes. Subsequently, ECG changes resolved coincidentally with the resolution
of chest pain. He was eventually diagnosed with pseudo-Wellens' syndrome. This
paper illustrates that physicians should be vigilant for Wellens' syndrome
mimicked by acute phencyclidine and cannabis intoxication. Additionally, we
present a review of various aetiologies of pseudo-Wellens' syndrome, especially
in patients with substance abuse.
PMID- 29960974
TI - Biot's breathing associated with acute bacterial meningitis in a child.
PMID- 29960975
TI - A case of massive haemoptysis.
PMID- 29960976
TI - Gas within the stomach wall and hepatic portal vein.
PMID- 29960977
TI - Subfoveal congenital hypertrophy of retinal pigment epithelium.
PMID- 29960978
TI - Variation in antinuclear antibody detection: need for clear expectations and
additional studies.
PMID- 29960979
TI - FISH studies in DLBCL: correlations with cell of origin: the Irish experience.
PMID- 29960980
TI - A family case with germline TSC1 and mtDNA mutations developing bilateral
eosinophilic chromophobe renal cell carcinomas without other typical phenotype of
tuberous sclerosis.
AB - AIM: We examined the genetic alterations in a mother and son with multiple
eosinophilic chromophobe renal cell carcinomas (chRCCs) showing no other
features. METHODS: Germline DNA and bilateral renal cell carcinoma DNA were
genetically analysed by whole-exome sequencing. Candidate gene alterations in the
first patient's germline were investigated in her child's germline and the
chRCCs. RESULTS: We detected several germline gene alterations in the mother.
Among the identified alterations, TSC1 and mitochondrial DNA mutations were also
confirmed in her son. Regarding somatic alterations in bilateral chRCCs, no
common candidate gene alteration was found. CONCLUSION: To the best of our
knowledge, this is the first report of whole-exome sequencing revealing bilateral
eosinophilic chRCCs associated with tuberous sclerosis complex in a family case
without classical phenotype. These results suggest that germline TSC1 and
mitochondrial DNA gene mutations may be involved in the development of chRCCs in
some cases.
PMID- 29960981
TI - Geographic variation in molecular subtype for gastric adenocarcinoma.
PMID- 29960982
TI - Examining unmet needs: a cross-sectional study exploring knowledge, attitudes and
sexually transmitted infection screening preferences among persons who inject
drugs in Camden, New Jersey.
AB - OBJECTIVES: To inform the development of targeted sexually transmitted infection
(STI) control programmes for persons who inject drugs (PWID). METHODS: We
recruited 116 PWID (aged >= 18 years) from a community-based syringe exchange
programme (SEP) and assessed their STI knowledge and screening preferences via
technology assisted self-interview. We estimated prevalence of STI transmission
knowledge, attitudes and screening preferences as well as the association between
reported sexual behaviours (past 6 months) and willingness to self-collect
specimens. RESULTS: Participants were white (77%), female (51%) and heterosexual
(77%). STI knowledge regarding transmission and testing was high among the
sample. More than 70% of participants were aware extragenital infections were
possible and were least likely to know urine tests do not detect rectal
infections (40.9%). Site-specific specimen collection was highly reflective of
reported sexual behaviour. PWID who reported receptive sex (36% vs 5%, p<0.01)
and insertive anal sex (31% vs 6%, p=0.01) were more likely to collect rectal
specimens than those who did not. A similar trend was seen for oral sex
performance on men and self-collection of oropharyngeal swabs (15% vs 3%,
p=0.04). In addition, participants preferred collecting their own sample to
having a clinician collect it for them (69% vs 31%, p<0.01) and testing at the
SEP compared with a STI clinic (86% vs 14%, p<0.01). CONCLUSION: Our findings
suggest site-specific specimen collection may be a proxy for risk behaviour
engagement in this fairly knowledgeable high-risk population. To increase case
finding, STI control programmes should educate patients about site-specific
screening and pair outreach with the infrastructure provided by SEPs, in settings
where these programmes exist.
PMID- 29960983
TI - Tibial bone density, cross-sectional geometry and strength in Finnish pet
rabbits: a peripheral quantitative computed tomography study.
AB - Rabbit bones are brittle and prone to fissure formation. Radiographs of very
young and old rabbits are often indicative of decreased bone density. The aim of
this study was to investigate the tibial bone parameters in pet rabbits, and
their association with age, sex, castration and dental disease. Eighty-seven (43
female/5 spayed, 44 male/19 castrated) pet rabbits (mean age 2.6 years, range 0.3
9.3 years) of various breeds were studied, of which 37 had dental disease. Right
tibiae were scanned with peripheral quantitative CT at the distal (4percent) and
mid-shaft sites (50percent of the tibial length). Analysed bone parameters
included the total cross-sectional area, cortical bone area and density,
trabecular bone density and strength-strain index. The mean diaphyseal cortical
density was high (about 1400 mg/cm3) in comparison to many other species. Within
the studied age range, age was weakly but positively associated with diaphyseal
cortical density, with the juvenile rabbits clearly showing the lowest values.
There was no tendency for age-related decrease in trabecular or cortical bone
density at least up to six years of age. Neither were sex, castration nor dental
disease associated with decreased tibial bone density.
PMID- 29960984
TI - Postpartum ketoprofen treatment does not alter stress biomarkers in cows and
calves experiencing assisted and unassisted parturition: a randomised controlled
trial.
AB - Dystocia is considered painful and stressful for both the dam and the calf,
although systematic evidence of this is limited. Few studies have investigated
biochemical markers of stress and pain postpartum and whether any adverse effects
are ameliorated by administration of analgesia. In this study, cow-calf pairs
experiencing both mild to moderate farmer assistance and no assistance at
parturition were randomly assigned to either treatment or placebo group in a two
by-two design (animals subject to veterinary intervention were excluded). The
treatments were the NSAID ketoprofen or saline, administered within three hours
of parturition. Blood samples taken in the immediate postpartum period, and at 24
hours, 48 hours and 7 days after parturition, were analysed for plasma
concentrations of creatine kinase and cortisol (cows and calves) and plasma L
lactate and total protein concentration (calves). Stress biomarkers were highest
in the immediate postpartum period and declined over time (P<0.05). Cow plasma
cortisol was higher in animals experiencing assisted parturition in the immediate
postpartum period (P=0.023); by 24 hours no difference was evident. Intervention
with NSAID analgesia did not result in beneficial changes in stress biomarkers.
Based on biomarkers alone, this suggests limited benefits of NSAID treatment in
unassisted or mild to moderately assisted parturition.
PMID- 29960985
TI - Relationship Between Plasma 8-OH-Deoxyguanosine and Cardiovascular Disease and
Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial.
AB - BACKGROUND: 8-Oxo-2'-deoxyguanosine (8-oxo-2'-dG) is a biomarker of oxidative DNA
damage that is associated with cardiovascular disease and premature mortality in
the general population. Although oxidative stress has a proven role in
cardiovascular complications in diabetes mellitus, evidence for a relationship
between plasma 8-oxo-2'-dG and major cardiovascular outcomes in diabetes mellitus
is weak. METHODS AND RESULTS: A case-cohort study was performed in 3766
participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes
and Vascular Disease: Preterax and Diamicron Modified Release Controlled
Evaluation) trial (ClinicalTrials.gov number NCT00145925). The hazard ratios for
mortality and major acute cardiovascular events were derived using Cox regression
models. During a median of 5 years of follow-up, 695 (18.4%) participants in this
enriched cohort died (including 354 deaths from cardiovascular disease).
Individuals with higher levels of 8-oxo-2'-dG were more likely to die. After
adjusting for cardiovascular disease risk factors, the hazard ratio for a 1-SD
increase in plasma 8-oxo-2'-dG was 1.10 (95% confidence interval, 1.01-1.20;
P=0.03). This was driven by an independent association between plasma 8-oxo-2'-dG
and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10-1.37
[P<0.001]). By contrast, no association was seen between 8-oxo-2'-dG and
noncardiovascular disease death (of which cancer was the major single cause). 8
Oxo-2'-dG was also not significantly associated with either nonfatal myocardial
infarction or nonfatal stroke. CONCLUSIONS: In adults with type 2 diabetes
mellitus, increased levels of 8-oxo-2'-dG are independently associated with all
cause mortality and cardiovascular mortality in adults with longstanding type 2
diabetes mellitus who participated in the ADVANCE trial, consistent with the role
of oxidative damage in the development and progression of cardiovascular
decompensation in diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00145925.
PMID- 29960986
TI - Delphi Analysis of Science Gaps in the 2015 American Heart Association Cardiac
Arrest Guidelines.
AB - BACKGROUND: Current cardiac arrest guidelines have limited high-quality
scientific evidence to support recommendations for care. The quality of
scientific evidence on which guidelines are based may correlate with improved
patient outcomes and meaningful survival. We sought to develop a prioritized list
of knowledge gaps in resuscitation to assist researchers, policy makers, and
funding agencies in their decision-making process. METHODS AND RESULTS: A 4-stage
modified Delphi method was used with a panel of cardiac arrest experts. Experts
addressed the prompt: "What are the top 3 gaps in knowledge involving cardiac
arrest care that should be research priorities for National Institutes of
Health/American Heart Association funding to have the greatest impact on public
health?" Knowledge gaps were identified in the initial round, rated in a second
round, and rank ordered in the third round, and they underwent final review and
consensus (final round). The outcome was 10 knowledge gaps, with prioritization
of the top 3 gaps. A total of 61 gaps, with 19 distinct themes, were identified
by participants. The 10 knowledge gaps most likely to affect public health
identified by the expert panel included, in order, the following:
telecommunicator cardiopulmonary resuscitation, hemodynamic monitoring for goal
directed resuscitation, reasons why bystanders fail to respond, optimization of
postarrest care, out-of-hospital cardiac arrest identification and response,
individualizing resuscitation strategies, predicting patients at risk, tools for
neuroprognostication, optimal airway management, and optimizing educational
strategies. CONCLUSIONS: Ten priorities for cardiac arrest research were
identified, but consensus was not reached on the prioritized top 3. Future
research should address these gaps to potentially improve resuscitation guideline
evidence quality.
PMID- 29960987
TI - Impact of Angiographic Residual Stenosis on Clinical Outcomes After New
Generation Drug-Eluting Stents Implantation: Insights From a Pooled Analysis of
the RESET and NEXT Trials.
AB - BACKGROUND: Previous intravascular ultrasound studies suggested the association
of stent underexpansion with increased risk of stent thrombosis and restenosis.
However, no previous study has addressed the association of the suboptimal
angiographic result with target-lesion revascularization (TLR) in patients
receiving new-generation drug-eluting stents (DES). METHODS AND RESULTS: RESET
(Randomized evaluation of sirolimus-eluting versus everolimus-eluting stent
trial) and NEXT (NOBORI biolimus-eluting versus XIENCE/PROMUS everolimus-eluting
stent trial) are prospective, multicenter, randomized "DES versus DES" trials;
3196 patients and 3235 patients were enrolled in the RESET and NEXT,
respectively. Using the pooled individual patient-level data, the current study
population consisted of 3679 patients who received single-lesion treatment using
new-generation DES such as everolimus-eluting stent and biolimus-eluting stent.
The study population was divided into 3 groups according to the residual in-stent
% diameter stenosis (%DS) after stent implantation by offline quantitative
coronary angiography assessed in a core angiographic laboratory (optimal group:
%DS <10%, intermediate group: %DS=10% to 20%, suboptimal group: %DS ?20%). The
cumulative 3-year incidence of TLR was significantly higher in the suboptimal
group than in the intermediate and optimal groups (9.8% versus 5.8% versus 5.7%,
log-rank P=0.004). Even after adjusting for the clinical, angiographic, and
procedural characteristics, the excess TLR risk of the suboptimal group relative
to the optimal group remained significant (hazard ratio: 1.65, 95% confidence
interval, 1.14-2.41, P=0.009). The excess TLR risk of the suboptimal group
relative to the optimal group was consistently seen across all the subgroups
including heavy calcification. CONCLUSIONS: The residual angiographic in-stent
%DS >=20% was associated with increased risk for TLR in patients treated with the
new-generation DES.
PMID- 29960988
TI - Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress,
Atherosclerosis, and Hypertension, Most Likely Mediated via an IL-1-Mediated
Mechanism.
AB - BACKGROUND: Hypertension is a complex condition and a common cardiovascular risk
factor. Dietary docosahexaenoic acid (DHA) modulates atherosclerosis and
hypertension, possibly via an inflammatory mechanism. IL-1 (interleukin 1) has an
established role in atherosclerosis and inflammation, although whether IL-1
inhibition modulates blood pressure is unclear. METHODS AND RESULTS: Male apoE-/-
(apolipoprotein E-null) mice were fed either a high fat diet or a high fat diet
plus DHA (300 mg/kg per day) for 12 weeks. Blood pressure and cardiac function
were assessed, and effects of DHA on wall shear stress and atherosclerosis were
determined. DHA supplementation improved left ventricular function, reduced wall
shear stress and oscillatory shear at ostia in the descending aorta, and
significantly lowered blood pressure compared with controls (119.5+/-7 versus
159.7+/-3 mm Hg, P<0.001, n=4 per group). Analysis of atheroma following DHA
feeding in mice demonstrated a 4-fold reduction in lesion burden in distal aortas
and in brachiocephalic arteries (P<0.001, n=12 per group). In addition, DHA
treatment selectively decreased plaque endothelial IL-1beta (P<0.01).
CONCLUSIONS: Our findings revealed that raised blood pressure can be reduced by
inhibiting IL-1 indirectly by administration of DHA in the diet through a
mechanism that involves a reduction in wall shear stress and local expression of
the proinflammatory cytokine IL-1beta.
PMID- 29960989
TI - Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased
Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All
Postural Tachycardia Syndrome Variants.
AB - BACKGROUND: Postural tachycardia syndrome (POTS) is a heterogeneous condition. We
stratified patients previously evaluated for POTS on the basis of supine resting
cardiac output (CO) or with the complaint of platypnea or "shortness of breath"
during orthostasis. We hypothesize that postural hyperventilation is one cause of
POTS and that hyperventilation-associated POTS occurs when initial reduction in
CO is sufficiently large. We also propose that circulatory abnormalities
normalize with restoration of CO2. METHODS AND RESULTS: Fifty-eight enrollees
with POTS were compared with 16 healthy volunteer controls. Low CO in POTS was
defined by a resting supine CO <4 L/min. Patients with shortness of breath had
hyperventilation with end tidal CO2 <30 Torr during head-up tilt table testing.
There were no differences in height or weight between control patients and
patients with POTS or differences between the POTS groups. Beat-to-beat blood
pressure was measured by photoplethysmography, and CO was measured by ModelFlow.
Systemic vascular resistance was defined as mean arterial blood pressure/CO. End
tidal CO2 and cerebral blood flow velocity of the middle cerebral artery were
only reduced during head-up tilt in the hyperventilation group, whereas blood
pressure was increased compared with control. We corrected the reduced end tidal
CO2 in hyperventilation by addition of exogenous CO2 into a rebreathing
apparatus. With added CO2, heart rate, blood pressure, CO, and systemic vascular
resistance in hyperventilation became similar to control. CONCLUSIONS: We
conclude that all POTS is related to decreased CO, decreased central blood
volume, and increased systemic vascular resistance and that a variant of POTS is
consequent to postural hyperventilation.
PMID- 29960990
TI - Extracellular Fluid Excess Is Significantly Associated With Coronary Artery
Calcification in Patients With Chronic Kidney Disease.
AB - BACKGROUND: Extracellular fluid (ECF) excess is an independent predictor of
cardiovascular morbidity in patients undergoing dialysis. This study aimed to
investigate the relationship between ECF status, which is affected by renal
function, and coronary artery calcification (CAC), which is a marker of
cardiovascular disease, in patients with chronic kidney disease (CKD). METHODS
AND RESULTS: A total of 1741 patients at all stages of pre-dialysis CKD from the
prospective observational cohort of CMERC-HI (Cardiovascular and Metabolic
Disease Etiology Research Center-High Risk) were analyzed for the association
between ECF status and CAC. ECF status was defined as extracellular water-to
total body water ratio (ECW/TBW) measured using bioelectrical impedance analysis.
ECF excess was defined as ECW/TBW >=0.390 or >=0.400 depending on its severity.
To define CAC, Agatston coronary artery calcium scores were measured. A total
coronary artery calcium score of >=400 was defined as CAC. The CKD stages were
defined according to estimated glomerular filtration rate calculated using the
CKD Epidemiology Collaboration equation. ECW/TBW and the proportion of ECF excess
increased with progressing CKD stages. Multivariable logistic regression analyses
showed that ECW/TBW was independently associated with CAC (per 0.01 increase of
ECW/TBW, odds ratio 1.168, 95% confidence interval, 1.079-1.264, P<0.001). The
adjusted R2 for predicting higher coronary artery calcium scores and CAC
significantly improved after ECW/TBW was added to conventional factors. This
association was further confirmed by net reclassification and integrated
discriminant improvements, sensitivity analysis, and subgroup analysis.
CONCLUSIONS: ECF status is independently associated with a high risk of CAC in
patients with CKD. STUDY REGISTRATION: URL: https://www.clinicaltrials.gov/.
Unique identifier: NCT02003781.
PMID- 29960991
TI - Cerebral Protection During Catheter Ablation of Ventricular Tachycardia in
Patients With Ischemic Heart Disease.
AB - BACKGROUND: Catheter ablation of ventricular tachycardia (VT) is associated with
the risk of cerebral embolism. The origin of periprocedural brain embolism in the
setting of VT ablation is often unknown and strategies to avoid it are sparse.
The aim of this study was to assess the safety and feasibility of an endovascular
2-filter-based cerebral protection system (CPS) in left ventricular VT ablation
procedures in patients with ischemic heart disease. Furthermore,
histopathological correlates of periprocedural embolization were investigated.
METHODS AND RESULTS: In this pilot study, 11 patients with ischemic heart disease
and sustained VT underwent left ventricular catheter ablation under CPS
surveillance. The placement of the CPS was conducted before the ablation
procedure via the right radial artery. The VT ablation procedure was performed
via a combined transaortic and transseptal approach. All VTs were successfully
ablated. Placement and retrieval of the CPS was successful and safe in all cases.
No periprocedural complications related to the CPS were observed and no
periprocedural transient ischemic attack or stroke occurred. Debris captured by
the CPS was detected in all patients. Histology revealed that acute thrombus was
the most common type of debris (91%), followed by arterial wall tissue (73%) and
foreign material (55%). Less frequently found were myocardium (27%),
calcification (9%), necrotic core (9%), and valve tissue (9%). CONCLUSIONS:
Cerebral protection during VT ablation seems to be safe and feasible. Ablation
procedures of VT are associated with embolization of embolic debris, which was
found in every patient.
PMID- 29960992
TI - Continuous ST-Monitoring Function of Implantable Cardioverter Defibrillator
Detects Silent Ischemia in Patients With Coronary Artery Disease.
AB - BACKGROUND: Newer implantable cardioverter defibrillators can monitor
intracardiac ECGs , but their ability to detect ischemia is unclear. This study
investigated the usefulness of implantable cardioverter defibrillators with an ST
monitoring function in coronary artery disease patients. METHODS AND RESULTS: We
conducted a prospective study of implantable cardioverter defibrillator patients
with the ST-monitoring function. One hundred seventy-three patients who received
implantable cardioverter defibrillators for primary or secondary prevention of
sudden cardiac death. All patients underwent medical examinations at least every
6 months, with standard 12-lead ECGs and device checks that included analysis of
the ST-monitoring function. Myocardial perfusion imaging or coronary angiography
was performed during the follow-up. The mean follow-up duration was 23.3+/-7.7
months. Significant ST changes occurred in 15 patients (8.7%), of whom 14 were
asymptomatic. The incidence of angina pectoris was significantly higher in the ST
change (+) group than that in the ST change (-) group (28.6% versus 7.2%,
P=0.03). In the patients who underwent myocardial perfusion imaging, the
sensitivity, specificity, and negative predictive value of the ST-monitoring
feature to detect ischemia were 75.0%, 72.5%, and 93.5%, respectively. The
sensitivity, specificity, and negative predictive value of the ST-monitoring
feature to predict residual stenosis evaluated using coronary angiography were
76.9%, 83.5%, and 97.5%, respectively. The percentage of patients with a septal
right ventricular lead was significantly lower in the ST change (+) group than in
the ST change (-) group (13.5% versus 33.5%, P=0.01). CONCLUSIONS: If
intracardiac ECGs ST changes are detected, it is necessary to use additional
modalities even in asymptomatic patients. CLINICAL TRIAL REGISTRATION: URL:
upload.umin.ac.jp. Unique identifier: UMIN000011824.
PMID- 29960993
TI - Lack of a Tricuspid Regurgitation Doppler Signal and Pulmonary Hypertension by
Invasive Measurement.
AB - BACKGROUND: Transthoracic echocardiography (TTE) is used to estimate pulmonary
artery systolic pressure, but an adequate tricuspid regurgitation velocity (TRV)
needed to calculate pulmonary artery systolic pressure is not always present. It
is unknown whether the absence of a measurable TRV signifies normal pulmonary
artery pressure. METHODS AND RESULTS: We extracted hemodynamic, TTE, and clinical
data from Vanderbilt's deidentified electronic medical record in all patients
referred for right heart catheterization between 1998 and 2014. Pulmonary
hypertension (PH) was defined as mean pulmonary artery pressure >=25 mm Hg. We
examined the prevalence and clinical correlates of PH in patients without a
reported TRV. We identified 1262 patients with a TTE within 2 days of right heart
catheterization. In total, 803/1262 (64%) had a reported TRV, whereas 459 (36%)
had no reported TRV. Invasively confirmed PH was present in 47% of patients
without a reported TRV versus 68% in those with a reported TRV (P<0.001). Absence
of a TRV yielded a negative predictive value for excluding PH of 53%. Right
ventricular dysfunction, left atrial dimension, elevated body mass index, higher
brain natriuretic peptide, diabetes mellitus, and heart failure were
independently associated with PH among patients without a reported TRV.
CONCLUSIONS: PH is present in almost half of patients without a measurable TRV
who are referred for both TTE and right heart catheterization. Clinical and
echocardiographic features of left heart disease are associated with invasively
confirmed PH in subjects without a reported TRV. Clinicians should use caution
when making assumptions about PH status in the absence of a measurable TRV on
TTE.
PMID- 29960994
TI - Discovery of an Experimental Model of Unicuspid Aortic Valve.
AB - BACKGROUND: The epithelial growth factor receptor family of tyrosine kinases
modulates embryonic formation of semilunar valves. We hypothesized that mice
heterozygous for a dominant loss-of-function mutation in epithelial growth factor
receptor, which are EgfrVel/+ mice, would develop anomalous aortic valves, valve
dysfunction, and valvular cardiomyopathy. METHODS AND RESULTS: Aortic valves from
EgfrVel/+ mice and control mice were examined by light microscopy at 2.5 to 4
months of age. Additional EgfrVel/+ and control mice underwent echocardiography
at 2.5, 4.5, 8, and 12 months of age, followed by histologic examination. In
young mice, microscopy revealed anatomic anomalies in 79% of EgfrVel/+ aortic
valves, which resembled human unicuspid aortic valves. Anomalies were not
observed in control mice. At 12 months of age, histologic architecture was
grossly distorted in EgfrVel/+ aortic valves. Echocardiography detected moderate
or severe aortic regurgitation, or aortic stenosis was present in 38% of
EgfrVel/+ mice at 2.5 months of age (N=24) and in 74% by 8 months of age. Left
ventricular enlargement, hypertrophy, and reversion to a fetal myocardial gene
expression program occurred in EgfrVel/+ mice with aortic valve dysfunction, but
not in EgfrVel/+ mice with near-normal aortic valve function. Myocardial fibrosis
was minimal or absent in all groups. CONCLUSIONS: A new mouse model uniquely
recapitulates salient functional, structural, and histologic features of human
unicuspid aortic valve disease, which are phenotypically distinct from other
forms of congenital aortic valve disease. The new model may be useful for
elucidating mechanisms by which congenitally anomalous aortic valves become
critically dysfunctional.
PMID- 29960995
TI - Long-Term Mortality of Older Patients With Acute Myocardial Infarction Treated in
US Clinical Practice.
AB - BACKGROUND: There is limited information about the long-term survival of older
patients after myocardial infarction (MI). METHODS AND RESULTS: CRUSADE (Can
rapid risk stratification of unstable angina patients suppress adverse outcomes
with early implementation of the ACC/AHA guidelines) was a registry of MI
patients treated at 568 US hospitals from 2001 to 2006. We linked MI patients
aged >=65 years in CRUSADE to their Medicare data to ascertain long-term
mortality (defined as 8 years post index event). Long-term unadjusted Kaplan
Meier mortality curves were examined among patients stratified by
revascularization status. A landmark analysis conditioned on surviving the first
year post-MI was conducted. We used multivariable Cox regression to compare
mortality risks between ST-segment-elevation myocardial infarction and non-ST
segment-elevation myocardial infarction patients. Among 22 295 MI patients >= age
65 years (median age 77 years), we observed high rates of evidence-based
medication use at discharge: aspirin 95%, beta-blockers 94%, and statins 81%.
Despite this, mortality rates were high: 24% at 1 year, 51% at 5 years, and 65%
at 8 years. Eight-year mortality remained high among patients who underwent
percutaneous coronary intervention (49%), coronary artery bypass graft (46%), and
among patients who survived the first year post-MI (59%). Median survival was 4.8
years (25th, 75th percentiles 1.1, 8.5); among patients aged 65-74 years it was
8.2 years (3.3, 8.9) while for patients aged >=75 years it was 3.1 years (0.6,
7.6). Eight-year mortality was lower among ST-segment-elevation myocardial
infarction than non-ST-segment-elevation myocardial infarction patients (53%
versus 67%); this difference was not significant after adjustment (hazard ratio
0.94, 95% confidence interval, 0.88-1.00). CONCLUSIONS: Long-term mortality
remains high among patients with MI in routine clinical practice, even among
revascularized patients and those who survived the first year.
PMID- 29960997
TI - Quality of life of extremely preterm school-age children without major handicap:
a cross-sectional observational study.
AB - OBJECTIVE: To determine the quality of life (QoL) of school-aged children who
were born <28+0 weeks of gestation and who have no resultant major disabilities.
DESIGN, SETTING AND PATIENTS: A cross-sectional multicentre study of extremely
preterm (EPT) infants born <28+0 weeks, discharged alive and free from severe
impairments (cerebral palsy, autism, major cognitive disabilities). Two generic,
self-evaluation and hetero-evaluation (by parent) QoL measurement questionnaires
(Kidscreen 10/VSP-A) were used and then compared with French population
reference. MAIN OUTCOME MEASURES: Clinical examination, an assessment of
cognitive functions and QoL between 7 and 10 years of age. RESULTS: 40 (7.5%)
severely disabled children were excluded. Among those 471 eligible, the lost to
follow-up group (169 (36%)) paralleled those 302 (64%) included in the study. The
mean gestational age was 26.2 (+/-0.8), birth weight was 879 (+/-181) g and the
mean age was 8.4 (+/-0.87) years. 48% of participants had minor or moderate
cognitive disabilities based on their Full-Scale Index Quotient. Working memory,
attention and mental flexibility scored as low-average. Except for family
relationships, the EPT QoL VSP-A and Kidscreen 10 assessment were significantly
lower based on the children's and parent's perspectives. Children reported the
most significant QoL decline as (1) friends' relationships, (2) self-esteem and
(3) leisure, while parents indicated (1) psychological well-being, (2) schoolwork
and (3) vitality. CONCLUSION: The QoL of a school-age EPT child without severe
impairment was lower relative to a reference population from both the parents'
and child's points of view. This evaluation should help to better understand the
long-term outcomes and to provide better support for them and their families.
TRIAL REGISTRATION NUMBER: NCT01675726, pre-results.
PMID- 29960996
TI - Systematic Review of Circulating, Biomechanical, and Genetic Markers for the
Prediction of Abdominal Aortic Aneurysm Growth and Rupture.
AB - BACKGROUND: The natural course of abdominal aortic aneurysms (AAA) is growth and
rupture if left untreated. Numerous markers have been investigated; however, none
are broadly acknowledged. Our aim was to identify potential prognostic markers
for AAA growth and rupture. METHODS AND RESULTS: Potential circulating,
biomechanical, and genetic markers were studied. A comprehensive search was
conducted in PubMed, Embase, and Cochrane Library in February 2017, following
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines. Study selection, data extraction, and methodological quality
assessment were conducted by 2 independent researchers. Plausibility of markers
was based on the amount of publications regarding the marker (more than 3),
pooled sample size (more than 100), bias risk and statistical significance of the
studies. Eighty-two studies were included, which examined circulating (n=40),
biomechanical (n=27), and genetic markers (n=7) and combinations of markers
(n=8). Factors with an increased expansion risk included: AAA diameter (9
studies; n=1938; low bias risk), chlamydophila pneumonia (4 studies; n=311;
medium bias risk), S-elastin peptides (3 studies; n=205; medium bias risk),
fluorodeoxyglucose uptake (3 studies; n=104; medium bias risk), and intraluminal
thrombus size (5 studies; n=758; medium bias risk). Factors with an increased
rupture risk rupture included: peak wall stress (9 studies; n=579; medium bias
risk) and AAA diameter (8 studies; n=354; medium bias risk). No meta-analysis was
conducted because of clinical and methodological heterogeneity. CONCLUSIONS: We
identified 5 potential markers with a prognostic value for AAA growth and 2 for
rupture. While interpreting these data, one must realize that conclusions are
based on small sample sizes and clinical and methodological heterogeneity.
Prospective and methodological consonant studies are strongly urged to further
study these potential markers.
PMID- 29960998
TI - Qualitative study of perspectives concerning recent rehospitalisations among a
high-risk cohort of veteran patients in Connecticut, USA.
AB - OBJECTIVES: Veterans Affairs (VA) patients are at risk for rehospitalisation due
to their lower socioeconomic status, older age, poor social support or multiple
comorbidities. The study explored inpatients' perceptions about factors
contributing to their rehospitalisation and their recommendations to reduce this
risk. DESIGN: Thematic qualitative data analysis of interviews with 18 VA
inpatients. SETTING: VA Connecticut Healthcare System, West Haven Hospital
medical inpatient units. PARTICIPANTS: All were aged 18+ years, rehospitalised
within 30 days of most recent discharge, medically stable and competent to
provide consent. MEASUREMENTS: Interviews assessed inpatients' health status
after last discharge, reason for rehospitalisation, access to and support from
primary care providers (PCP), medication management, home support systems and
history of substance use or mental health disorders. RESULTS: The mean age was
71.6 years (11.1 SD); all were Caucasian, living on limited budgets, and many had
serious medical conditions or histories of mental health disorders. Participants
considered structural barriers to accessing PCP and limited PCP involvement in
medical decision-making as contributing to their rehospitalisation, although most
believed that rehospitalisation had been inevitable. Peridischarge themes
included beliefs about premature discharge, inadequate understanding of
postdischarge plans and insufficiently coordinated postdischarge services. Most
highly valued their VA healthcare but recommended increasing PCPs' involvement
and reducing structural barriers to accessing primary and specialty care.
CONCLUSIONS: Increased PCP involvement in medical decision-making about
rehospitalisation, expanded clinic hours, reduced travel distances, improved
communications to patients and their families about predischarge and
postdischarge plans and proactive postdischarge outreach to high-risk patients
may reduce rehospitalisation risk.
PMID- 29960999
TI - Health-related quality of life and psychosocial impacts of a diagnosis of non
specific genital infection in symptomatic heterosexual men attending UK sexual
health clinics: a feasibility study.
AB - INTRODUCTION: Non-specific genital infection (NSGI; non-Chlamydia trachomatis,
non-Neisseria gonorrhoeae-associated urethritis) is a common diagnosis in
symptomatic heterosexual men attending UK sexual health clinics (SHCs). but
little is known about the psychosocial impact of this diagnosis. METHODS: We
conducted an observational study among symptomatic heterosexual men attending
SHCs to evaluate the psychosocial impact of an NSGI diagnosis compared with a
diagnosis of Chlamydia trachomatis (CT), Neisseria gonorrhoeae or no
abnormalities detected focusing on the feasibility of our study methodology.
Participants completed a computer-assisted self-interviewing (CASI) including two
validated measures of psychosocial impact: the EQ-5D-5L health-related quality of
life and Rosenberg Self-Esteem Scale, before diagnostic testing and 2 weeks after
receiving test results (follow-up 1 (FU-1)) and a qualitative interview. We
compared scores between diagnostic groups using paired t-tests, qualitative data
were analysed thematically and feasibility was assessed by process analysis.
RESULTS: 60 men completed the baseline CASI (75% response rate). 46 (76.6%) were
eligible for follow-up; 11/46 (23.9%) completed the follow-up CASI, and 3/11
(27.3%) completed the qualitative interview. 81.7% of all participants left CASI
feedback at baseline: 73.5% reported the questionnaire as 'fine' or 'very good'.
Qualitative interview participants reported the study was acceptable. Compared
with baseline, among patients completing FU-1, only patients with a diagnosis of
NSGI (p<0.05) or CT (p<0.05) showed increased EQ-5D-5L Index, whereas patients
with a diagnosis of NSGI (p=0.05) showed decreased mean Rosenberg Self-Esteem
Scale score. CONCLUSIONS: Although most participants indicated study
acceptability at baseline, and we employed measures to increase retention (CASI
questionnaires, reminder messages and a focus on men's health), we experienced
high loss to follow-up. We found that heterosexual men attending SHCs with
symptoms of urethritis experience both positive and negative psychosocial impacts
following their clinic attendance, which warrants further investigation.
PMID- 29961000
TI - Associations of disaster-related and psychosocial factors with changes in smoking
status after a disaster: a cross-sectional survey after the Great East Japan
Earthquake.
AB - OBJECTIVE: Few studies have comprehensively examined changes in smoking status
and related factors after a disaster. We examined these factors among residents
of an evacuation area in Fukushima after the Great East Japan Earthquake.
METHODS: The study participants included 58 755 men and women aged >=20 years who
participated in the Fukushima Health Management Survey in 2012 after the
disaster. Smoking status was classified as either current smokers or current non
smokers before and after the disaster. The participants were divided into the
following groups: (1) non-smokers both before and after the disaster, (2) non
smokers before and smokers after the disaster, (3) smokers before and non-smokers
after the disaster and (4) smokers both before and after the disaster. The
adjusted prevalence ratios and 95% CIs of changes in smoking status for
demographic, disaster-related and psychosocial factors were tested using logistic
regression analysis that was stratified by smoking status before the disaster.
RESULTS: Among the 44 729 participants, who were non-smokers before the disaster,
634 (1.4%) began smoking after the disaster. Among the 14 025 smokers before the
disaster, 1564 (11.1%) quit smoking after the disaster, and the proportion of
smokers in the evacuation area consequently decreased from 21.2% to 19.6%. In the
multivariable model, factors significantly associated with beginning smoking
included being a male, being younger, having a lower education, staying in a
rental house/apartment, house being damaged, having experienced a tsunami, change
jobs and the presence of traumatic symptoms and non-specific psychological
distress. On the contrary, factors associated with quitting smoking included
being a female, being older, having a higher education and having a stable
income. CONCLUSION: The proportion of smokers slightly decreased among residents
in the evacuation area. The changes in smoking statuses were associated with
disaster-associated psychosocial factors, particularly changes in living
conditions, having experienced a tsunami, change jobs and developing post
traumatic stress disorder.
PMID- 29961001
TI - History and publication trends in the diffusion and early uptake of indirect
comparison meta-analytic methods to study drugs: animated coauthorship networks
over time.
AB - OBJECTIVE: To characterise the early diffusion of indirect comparison meta
analytic methods to study drugs. DESIGN: Systematic literature synthesis. DATA
SOURCES: Cochrane Database of Systematic Reviews, EMBASE, MEDLINE, Scopus and Web
of Science. STUDY SELECTION: English language papers that used indirect
comparison meta-analytic methods to study the efficacy or safety of three or more
interventions, where at least one was a drug. DATA EXTRACTION: The number of
publications and authors was plotted by year and type: methodological
contribution, review or empirical application. Author and methodological details
were summarised for empirical applications, and animated coauthorship networks
were created to visualise contributors by country and affiliation type (academia,
industry, government or other) over time. RESULTS: We identified 477 papers (74
methodological contributions, 42 reviews and 361 empirical applications) by 1689
distinct authors from 1997 to 2013. Prior to 2002, only three applications were
published, with contributions from the USA (n=2) and Canada (n=1). The number of
applications gradually increased annually with rapid uptake between 2011 and 2013
(n=254, 71%). Early diffusion occurred primarily in Europe with the first
application credited to the UK in 2003. Application spread to other European
countries in 2005, and may have been supported by regulatory requirements for
drug approval. By the end of 2013, contributions included 49% credited to Europe
(22% UK, 27% other), 37% credited to North America (11% Canada, 26% USA) and 14%
from other regions. CONCLUSION: Indirect comparison meta-analytic methods are an
important innovation for health research. Although Canada and the USA were the
first to apply these methods, Europe led their diffusion. The increase in uptake
of these methods may have been facilitated by acceptance by regulatory agencies,
which are calling for more comparative drug effect data to assist in drug
accessibility and reimbursement decisions.
PMID- 29961002
TI - Acute kidney injury in the UK: a replication cohort study of the variation across
three regional populations.
AB - OBJECTIVES: A rapid growth in the reported rates of acute kidney injury (AKI) has
led to calls for greater attention and greater resources for improving care.
However, the reported incidence of AKI also varies more than tenfold between
previous studies. Some of this variation is likely to stem from methodological
heterogeneity. This study explores the extent of cross-population variation in
AKI incidence after minimising heterogeneity. DESIGN: Population-based cohort
study analysing data from electronic health records from three regions in the UK
through shared analysis code and harmonised methodology. SETTING: Three
populations from Scotland, Wales and England covering three time periods:
Grampian 2003, 2007 and 2012; Swansea 2007; and Salford 2012. PARTICIPANTS: All
residents in each region, aged 15 years or older. MAIN OUTCOME MEASURES:
Population incidence of AKI and AKI phenotype (severity, recovery, recurrence).
Determined using shared biochemistry-based AKI episode code and standardised by
age and sex. RESULTS: Respectively, crude AKI rates (per 10 000/year) were 131,
138, 139, 151 and 124 (p=0.095), and after standardisation for age and sex: 147,
151, 146, 146 and 142 (p=0.257) for Grampian 2003, 2007 and 2012; Swansea 2007;
and Salford 2012. The pattern of variation in crude rates was robust to any
modifications of the AKI definition. Across all populations and time periods, AKI
rates increased substantially with age from ~20 to ~550 per 10 000/year among
those aged <40 and >=70 years. CONCLUSION: When harmonised methods are used and
age and sex differences are accounted for, a similar high burden of AKI is
consistently observed across different populations and time periods (~150 per 10
000/year). There are particularly high rates of AKI among older people. Policy
makers should be careful not draw simplistic assumptions about variation in AKI
rates based on comparisons that are not rigorous in methodological terms.
PMID- 29961003
TI - Association between recreational drug use and sexual practices among people who
inject drugs in Southwest China: a cross-sectional study.
AB - OBJECTIVE: To describe the differences in sexual practices among individuals with
various drug administration patterns. SETTING: A detoxification centre in
Southwest China, a part of the Chinese national sentential surveillance network
for hepatitis C virus (HCV), HIV and syphilis infections, was recruited.
PARTICIPANTS: A total of 610 newly enrolled injection drug users (IDUs) from
detoxification centre were included during 2015. PRIMARY AND SECONDARY OUTCOME
MEASURES: Self-reported sexual activities, drug-related practices and laboratory
confirmed HCV, HIV and syphilis infection status were collected. RESULTS: Of the
610 IDU, 295 (48.4%) used heroin only, 277 (45.4%) poly-drug users reported the
mixed use of synthetic drugs (SDs) with heroin and 38 (6.2%) used SDs only. The
average daily drug injection frequency for poly-drug users (3.3+/-1.2 times) was
the highest, followed by heroin-only (2.2+/-0.8 times) and SD-only users (1.2+/
0.4 time). SD-only drug users reported the highest proportion (86.8%) of engaging
in sexual activities in the previous month, with more than half (54.5%) reporting
any condomless sex. A higher frequency of daily injecting in heroin-only users
was significantly correlated with the less likelihood of sex, condomless sex in
the past month, having sex with fixed partners, condomless commercial sex in the
previous 12 months (all p<0.01). In poly-drug users, who injected drugs two times
per day was associated with the highest proportion of people who engaged in sex
and commercial sex (p<0.05). For SD-only users, increased drug use was not
associated with reducing sexual risk (p>0.05). Different patterns of HCV, HIV and
syphilis infections prevalence rates were shown among the IDU depending on the
roles and length of exposure. CONCLUSIONS: The daily drug injecting frequency of
heroin-only and poly-drug users was negatively associated with sexual activities,
but SD-only users kept a high frequent engagement in sex. The interventions for
relevant diseases should adapt to characteristics of IDU.
PMID- 29961004
TI - Augmenting inpatient treatment for post-traumatic stress disorder with a
computerised cognitive bias modification procedure targeting appraisals (CBM
App): protocol for a randomised controlled trial.
AB - INTRODUCTION: Influential theories of post-traumatic stress disorder (PTSD)
suggest that dysfunctional appraisals of trauma play a key role in the
maintenance of symptoms, and this suggestion is increasingly supported by
research. Experimental studies have indicated that a simple computerised
cognitive training procedure, here termed cognitive bias modification-appraisals
(CBM-App), can modify trauma-relevant appraisals and reduce analogue trauma
symptoms among healthy volunteers. This suggests the possibility that CBM-App
could improve outcomes in PTSD via targeting the key process of dysfunctional
appraisals, for example, if applied as an adjunct to treatment. METHODS AND
ANALYSIS: The study is a randomised controlled trial with two parallel arms. It
is planned to randomise 80 patients admitted for treatment for PTSD to an
inpatient treatment clinic to complete either sessions of CBM-App or a sham
training control condition, the peripheral vision task. Both interventions
comprise eight sessions scheduled over a 2-week period and are completed in
addition to the standard treatment programme in the clinic. Outcome assessment
occurs pretraining, after 1 week of training, post-training, at discharge from
the inpatient clinic and 6 weeks and 3 months postdischarge. The primary outcome
is dysfunctional trauma-relevant appraisals at post-training, measured using a
scenario completion task. Secondary outcomes include symptom measures and hair
cortisol. Outcome analyses will be primarily via mixed linear models and
conducted with both intention to treat and per protocol samples. ETHICS AND
DISSEMINATION: The trial has been approved by the Ethics Committee for the
Faculty of Psychology, Ruhr-Universitat Bochum (approval no 204) and the Ethics
Committee for the Faculty of Medicine, Ruhr-Universitat Bochum (approval no 15
5477). Results will be published in peer-reviewed journals and will inform future
clinical and experimental studies into targeting maladaptive appraisals for the
reduction of PTSD symptoms. TRIAL REGISTRATION NUMBER: NCT02687555.
PMID- 29961005
TI - Equity and efficiency in the scaled-up implementation of integrated neglected
tropical disease control: the health economics protocol of the COUNTDOWN
multicountry observational study in Ghana, Cameroon and Liberia.
AB - INTRODUCTION: Worldwide, millions of individuals are affected by neglected
tropical diseases (NTDs). They are frequently the poorest and most marginalised
members of society. Their living conditions, among other things, make them
susceptible to such diseases. Historically, several large-scale treatment
programmes providing mass drug administrations (MDAs) were carried out per single
disease but over the last decade there has been an increasing trend towards co
implementation of MDA activities given the resources used for such programmes are
often the same. The COUNTDOWN multicountry studies focus on scaled-up
implementation of integrated control strategies against four diseases: lymphatic
filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis.
The objective of the COUNTDOWN economic study is to assess the multicountry
implementation of control interventions in terms of equity, impact and
efficiency. METHODS: The health economic study uses different analytical methods
to assess the relationship between NTDs and poverty and the cost-effectiveness of
different large-scale intervention options. Regression analysis will be used to
study the determinants of NTD occurrence, the impact of NTDs on poverty, factors
that hinder access to MDAs and the effect of NTDs on quality-of-life of those
affected, including disability. Cost-effectiveness analyses of various
integration methods will be performed using health economic modelling to estimate
the cost and programme impact of different integration options. Here, cost
effectiveness ratios will be calculated, including multivariate sensitivity
analyses, using Bayesian analysis. ETHICS AND DISSEMINATION: Ethics approval has
been received both at the Liverpool School of Tropical Medicine and in all
participating countries. Results of the various substudies will be presented for
publication in peer-reviewed journals. STUDY DATES: 1 July 2016 to 30 June
October 2019.
PMID- 29961006
TI - Factors associated with continued smoking after the diagnosis of type 2 diabetes:
a retrospective study in the Korean cohort.
AB - OBJECTIVE: To investigate the factors associated with continued smoking in
patients newly diagnosed with type 2 diabetes. DESIGN: Retrospective study using
the Korean National Health Insurance Service-National Health Screening Cohort
(2002-2013) database. PARTICIPANTS: Male patients newly diagnosed with type 2
diabetes between 1 January 2004 and 31 December 2011. MEASUREMENT: Change in
smoking behaviour after the diabetes diagnosis was assessed using a self-reported
questionnaire, which was administered before and after the diagnosis. To identify
the factors associated with continued smoking after diabetes diagnosis, a
multivariate-adjusted logistic regression was conducted using only the variables
with statistical significance from the univariate analyses. RESULTS: Younger age,
lower economic status, heavier smoking habit, lower Charlson Comorbidity Index
and comorbid hypertension were identified as factors associated with continued
smoking after the diagnosis of type 2 diabetes. Older patients (adjusted OR (aOR)
0.71, 95% CI 0.63 to 0.79) and patients with longer diabetic duration (1-2 years
OR 0.88, 95% CI 0.80 to 0.98, >=3 years OR 0.63, 95% CI 0.55 to 0.73) were more
likely to quit smoking. Contrastingly, smokers in the lower economic status (aOR
1.29, 95% CI 1.18 to 1.42) and heavier smoking habit (moderate: aOR 1.53, 95% CI
1.35 to 1.72; heavy: aOR 1.90, 95% CI 1.67 to 2.17) categories were more likely
to continue smoking after the diagnosis. CONCLUSIONS: It is important to identify
the factors associated with smoking behaviour in patients with type 2 diabetes.
Recognising the factors that contribute to the vulnerability of patients to
continued smoking will be helpful in developing policies and intervention
strategies in future. Vulnerable patients may require intensive education and
encouragement to quit smoking. We recommend physicians to take a more proactive
approach, such as encouraging frequent clinical sessions for behavioural
counselling and even early pharmacological interventions, when they encounter
patients with the factors outlined in this study.
PMID- 29961007
TI - Common mental disorders among Indigenous people living in regional, remote and
metropolitan Australia: a cross-sectional study.
AB - OBJECTIVE: To determine, using face-to-face diagnostic interviews, the prevalence
of common mental disorders (CMD) in a cohort of adult Indigenous Australians, the
cultural acceptability of the interviews, the rates of comorbid CMD and
concordance with psychiatrists' diagnoses. DESIGN: Cross-sectional study July
2014-November 2016. Psychologists conducted Structured Clinical Interviews for
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
Revision Axis I Disorders (SCID-I) (n=544). Psychiatrists interviewed a subsample
(n=78). SETTING: Four Aboriginal Medical Services and the general community
located in urban, regional and remote areas of Southern Queensland and two
Aboriginal Reserves located in New South Wales. PARTICIPANTS: Indigenous
Australian adults. OUTCOME MEASURES: Cultural acceptability of SCID-I interviews,
standardised rates of CMD, comorbid CMD and concordance with psychiatrist
diagnoses. RESULTS: Participants reported that the SCID-I interviews were
generally culturally acceptable. Standardised rates (95% CI) of current mood,
anxiety, substance use and any mental disorder were 16.2% (12.2% to 20.2%), 29.2%
(24.2% to 34.1%), 12.4% (8.8% to 16.1%) and 42.2% (38.8% to 47.7%), respectively
6.7-fold, 3.8-fold, 6.9-fold and 4.2-fold higher, respectively, than those of the
Australian population. Differences between this Indigenous cohort and the
Australian population were less marked for 12-month (2.4-fold) and lifetime
prevalence (1.3-fold). Comorbid mental disorder was threefold to fourfold higher.
In subgroups living on traditional lands in Indigenous reserves and in remote
areas, the rate was half that of those living in mainstream communities. Moderate
to-good concordance with psychiatrist diagnoses was found. CONCLUSIONS: The
prevalence of current CMD in this Indigenous population is substantially higher
than previous estimates. The lower relative rates of non-current disorders are
consistent with underdiagnosis of previous events. The lower rates among Reserve
and remote area residents point to the importance of Indigenous peoples'
connection to their traditional lands and culture, and a potentially important
protective factor. A larger study with random sampling is required to determine
the population prevalence of CMD in Indigenous Australians.
PMID- 29961008
TI - Changes in antipsychotic drug usage and factors affecting the use of typical
drugs based on nationwide health insurance data in South Korea.
AB - OBJECTIVES: To determine changes in antipsychotic drug usage in all South Korean
patients with schizophrenia in 2011-2015 and factors affecting their utilisation
in 2015. DESIGN AND SETTING: Retrospective cohort study using health insurance
claims data on patients with schizophrenia in South Korea in 2011-2015.
PARTICIPANTS: All treated patients with schizophrenia in South Korea in 2011
2015. The number of patients with schizophrenia was 171 302 in 2011, 175 488 in
2012, 177 763 in 2013, 180 079 in 2014 and 183 427 in 2015. MAIN OUTCOME
MEASURES: Changes in antipsychotic drug usage and factors affecting the use of
antipsychotics. RESULTS: Among patients with schizophrenia, there were tendencies
of decreased use of antipsychotic combination therapy of typical drugs (from
11.5% to 7.5%) but increased use of combination therapy of atypical drugs (from
21.8% to 29.0%). Factors affecting the use of typical drugs were sex, age,
geographical region, type of benefits/insurances and type of medical
institutions. Use of typical antipsychotics was increased by age (OR=1.02, 95% CI
1.02 to 1.02). It was higher in men (OR=1.27, 95% CI 1.23 to 1.30) than that in
women. It was higher in Medicaid benefiters (OR=4.49, 95% CI 4.35 to 4.64) than
that in patients with health insurance. Use of typical drugs was higher among
patients treated in general hospitals (OR=1.46, 95% CI 1.32 to 1.64), primary
hospitals (OR=3.25, 95% CI 2.95 to 3.59), long-term care hospitals (OR=3.00, 95%
CI 2.59 to 3.49) and clinics (OR=8.87, 95% CI 8.06 to 9.76) compared with that in
tertiary care hospitals. Compared with metropolitan region, higher use of typical
antipsychotics was seen in Gangwon (OR=1.14, 95% CI 1.05 to 1.25), Jeolla
(OR=1.32, 95% CI 1.26 to 1.39) and Gyeongsang (OR=1.14, 95% CI 1.10 to 1.18)
provinces. CONCLUSIONS: Results of this study confirmed changes of antipsychotic
drug usage from typical to atypical antipsychotics in the treatment of
schizophrenia and identified factors affecting the use of typical drugs, in
contrast with current treatment trend in South Korea. These results may be used
in the improvement of a medical system.
PMID- 29961010
TI - Statewide cross-sectional survey of emergency departments' adoption and
implementation of the Ohio opioid prescribing guidelines and opioid prescribing
practices.
AB - STUDY OBJECTIVE: To evaluate the implementation of the Ohio Emergency and Acute
Care Facility Opioids and Other Controlled Substances Prescribing Guidelines and
their perceived impact on local policies and practice. METHODS: The study design
was a cross-sectional survey of emergency department (ED) medical directors, or
appropriate person identified by the hospital, perception of the impact of the
Ohio ED Opioid Prescribing Guidelines on their departments practice. All
hospitals with an ED in Ohio were contacted throughout October and November 2016.
Distribution followed Dillman's Tailored Design Method, augmented with telephone
recruitment. Hospital chief executive officers were contacted when necessary to
encourage ED participation. Descriptive statistics were used to assess the impact
of opioid prescribing policies on prescribing practices. RESULTS: A 92% response
rate was obtained (150/163 EDs). In total, 112 (75%) of the respondents stated
that their ED has an opioid prescribing policy, is adopting one or is
implementing prescribing guidelines without a specific policy. Of these 112 EDs,
81 (72%) based their policy on the Ohio ED Opioid Prescribing Guidelines. The
majority of respondents strongly agreed/agreed that the prescribing guidelines
have increased the use of the prescription drug monitoring programme (86%) and
have reduced inappropriate opioid prescribing (71%). CONCLUSION: This study
showed that the Ohio ED Opioid Prescribing Guidelines have been widely
disseminated and that the majority of EDs in Ohio are using them to develop local
policies. The majority of respondents believed that the Ohio opioid prescribing
guidelines reduced inappropriate opioid prescribing. However, prescribing
practices still varied greatly between EDs.
PMID- 29961009
TI - A systematic review of epigenetic biomarkers in progression from non-dysplastic
Barrett's oesophagus to oesophageal adenocarcinoma.
AB - OBJECTIVES: The objective of this systematic review is to identify and summarise
studies which examine epigenetic biomarkers in patients with Barrett's oesophagus
(BO) and their association with progression to oesophageal adenocarcinoma (OADC).
BO is a precursor lesion for OADC. There is no clinical test to predict patients
who are likely to progress to OADC. An epigenetic biomarker could predict
patients who are at high risk of progression from BO to OADC which could
facilitate earlier diagnosis and spare those unlikely to develop cancer from
regular invasive surveillance endoscopy. SETTING: A systematic search was
conducted of the following databases: MEDLINE, MEDLINE in Process, EMBASE,
Cochrane Central, ISI Conference Proceedings Citation Index and the British
Library's ZETOC. Studies were conducted in secondary and tertiary care settings.
PARTICIPANTS: All studies measuring epigenetic change in patients over 18 years
old who progressed from non-dysplastic BO to OADC were included. Genetic, in
vitro and studies which did not measure progression in the same patient cohort
were excluded. Study inclusion and risk of bias of individual eligible studies
were assessed in duplicate by two reviewers using a modified Quality in
Prognostic Studies tool. RESULTS: 14 studies met the inclusion criteria. 42
epigenetic markers were identified, and 5 studies developed models aiming to
predict progression to OADC. CONCLUSIONS: The evidence from this systematic
review is suggestive of a role for p16 as an epigenetic biomarker for the
progression of BO to OADC. PROSPERO NUMBER: CRD42016038654.
PMID- 29961011
TI - Outpatient antibiotic use in Dutch infants after 10-valent pneumococcal vaccine
introduction: a time-series analysis.
AB - OBJECTIVE: This population-based cohort study assesses the impact of switching
from a 7-valent pneumococcal conjugate vaccine (PCV) to a 10-valent PCV on
outpatient antibiotic use in Dutch infants, and whether geographical vaccination
coverage modifies this association. SETTING AND PARTICIPANTS: We extracted 2006
2013 anonymised antibiotic purchase data of 255 154 Dutch infants aged below 2
years from Achmea Health, a health insurance fund covering 28% of the national
population. DESIGN AND MAIN OUTCOME MEASURE: Changes in monthly antibiotic use
from 2006-2011 (PCV7) to 2011-2013 (PCV10) were estimated using time-series
analysis accounting for seasonality and autocorrelation. Interaction terms for
vaccination coverage (categorised into seven groups) and period were added to the
model to test whether this association was vaccination coverage-dependent.
RESULTS: 275 337 antibiotic courses were used by 119 078 infants (461 352 person
years). PCV10 introduction was associated with a modest 1.6% overall reduction in
antibiotic use (purchase rate ratio: 0.98, 95% CI: 0.98 to 0.99). Our model
showed a significant difference in time trend in antibiotic use after PCV10
introduction (p=0.0084) with an increase in prescriptions in the PCV7 period
(slope: 0.0023/month, 95% CI: -0.0001 to 0.0047) versus a decline in the PCV10
period (slope: -0.0089/month, 95% CI: -0.0150 to -0.0029). There was no evidence
that PCV vaccination coverage affected this association, but since the largest
rate ratios were observed in municipalities with the lowest vaccine coverage and
had very wide accompanying CIs, our study might have insufficient power to detect
such an association. CONCLUSIONS: Switching from PCV7 to PCV10 was associated
with a modest decline in outpatient antibiotic use in Dutch infants.
PMID- 29961012
TI - Treatment and persistence with oral anticoagulants among newly diagnosed patients
with non-valvular atrial fibrillation: a retrospective observational study in a
US commercially insured and Medicare Advantage population.
AB - OBJECTIVES: With the approval of new non-vitamin K antagonist oral anticoagulants
for stroke prevention in non-valvular atrial fibrillation (NVAF), it is
anticipated that their introduction may change NVAF treatment patterns; however,
there is limited supporting real-world evidence. This study investigated
guideline-recommended oral anticoagulation (OAC) treatment and persistence in
newly diagnosed patients with NVAF to understand demographic and clinical
characteristics. DESIGN: Retrospective observational administrative claims study
in the USA. SETTING: Patients with NVAF with >=1 pharmacy claim for OAC
(warfarin, dabigatran, rivaroxaban or apixaban) and no atrial fibrillation
diagnosis within 12 months prior to the first claim were identified in the
HealthCore Integrated Research Database between 1 November 2010 and 30 November
2013. PARTICIPANTS: 45 092 patients with NVAF were included. OUTCOMES: The
proportion of OAC-treated patients was stratified by CHADS2 score. Treatment
persistence was measured from OAC initiation to discontinuation, end of
eligibility or end of study period (30 November 2014), whichever occurred first.
RESULTS: Almost half of the patients (41.1%) received an OAC. The proportion
treated differed slightly in baseline stroke risk (CHADS2<2: 39.8%; CHADS2=2 or
3: 42.4%; and CHADS2>3: 40.3%: p<0.001). Treated patients were slightly younger
(70+/-12.2 vs 71+/-14.3 years; p<0.001), more likely male (59.7% vs 52.5%;
p<0.001) and had a slightly elevated stroke risk (CHADS2: 2.03+/-1.3 vs 1.98+/
1.4; p<0.001) and a lower bleeding risk (HEMORR2HAGES: 2.55+/-1.8 vs 2.80+/-1.9;
p<0.001) relative to untreated patients. Overall, patients with higher CHADS2
scores had higher HEMORR2HAGES scores. The mean follow-up was 2.25 years (2.25+/
0.85) and 72.7% of patients discontinued OACs; nearly 25% within 3 months and 55%
within 12 months. The mean time to discontinuation was 255+/-249 days.
CONCLUSIONS: The proportion of patients with NVAF who received OAC treatment was
lower than previously reported and differed slightly by stroke risk. Patients
with an elevated stroke risk had a higher bleeding risk, suggesting that
clinicians may incorporate both in the treatment decision.
PMID- 29961013
TI - Systematic review and meta-analysis of the effect of SGLT-2 inhibitors on
microvascular outcomes in patients with type 2 diabetes: a review protocol.
AB - INTRODUCTION: Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a relatively
new drug-class of glucose-lowering medications. Several trials and systematic
reviews have demonstrated their beneficial effect on some macrovascular outcomes.
Their effect on microvascular outcomes has been reported as positive in several
trials, however, their effect remains uncertain. Therefore, we report the
protocol of a systematic review and meta-analysis aimed at determining the effect
of SGLT-2 inhibitors regarding patient-important and surrogate microvascular
outcomes in patients with type 2 diabetes. METHODS AND ANALYSIS: A comprehensive
search will be conducted to find eligible articles from each database's earliest
inception to November 2017. These databases will include Ovid, MEDLINE, EMBASE,
Web of Science, and Scopus. We will search for randomized controlled trials
(RCTs) that compare any of the SGLT-2 inhibitors with any other active treatment
or placebo assessing microvascular outcomes in either their primary or secondary
outcomes. Reviewers working independently and in duplicate will review all
abstracts, and full-text manuscripts for eligibility, and will systematically
extract the data and will assess the risk of bias in the included studies. Random
effects models will also be used. ETHICS AND DISSEMINATION: The results of the
systematic review will be disseminated via publication in a peer-reviewed journal
regardless of outcome and will be presented at relevant conferences. The data we
will use do not include individual patient data, so ethical approval is not
required PROSPERO REGISTRATION NUMBER: CRD42017076460.
PMID- 29961014
TI - Accuracy and utility of using administrative healthcare databases to identify
people with epilepsy: a protocol for a systematic review and meta-analysis.
AB - INTRODUCTION: In an increasingly digital age for healthcare around the world,
administrative data have become rich and accessible tools for potentially
identifying and monitoring population trends in diseases including epilepsy.
However, it remains unclear (1) how accurate administrative data are at
identifying epilepsy within a population and (2) the optimal algorithms needed
for administrative data to correctly identify people with epilepsy within a
population. To address this knowledge gap, we will conduct a novel systematic
review of all identified studies validating administrative healthcare data in
epilepsy identification. We provide here a protocol that will outline the methods
and analyses planned for the systematic review. METHODS AND ANALYSIS: The
systematic review described in this protocol will be conducted to follow the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines. MEDLINE and Embase will be searched for studies validating
administrative data in epilepsy published from 1975 to current (01 June 2018).
Included studies will validate the International Classification of Disease (ICD),
Ninth Revision (ICD-9) onwards (ie, ICD-9 code 345 and ICD-10 codes G40-G41) as
well as other non-ICD disease classification systems used, such as Read Codes in
the UK. The primary outcome will be providing pooled estimates of accuracy for
identifying epilepsy within the administrative databases validated using
sensitivity, specificity, positive and negative predictive values, and area under
the receiver operating characteristic curves. Heterogeneity will be assessed
using the I2 statistic and descriptive analyses used where this is present. The
secondary outcome will be the optimal administrative data algorithms for
correctly identifying epilepsy. These will be identified using multivariable
logistic regression models. 95% confidence intervals will be quoted throughout.
We will make an assessment of risk of bias, quality of evidence, and completeness
of reporting for included studies. ETHICS AND DISSEMINATION: Ethical approval is
not required as primary data will not be collected. Results will be disseminated
in peer-reviewed journals, conference presentations and in press releases.
PROSPERO REGISTRATION: CRD42017081212.
PMID- 29961015
TI - POFA trial study protocol: a multicentre, double-blind, randomised, controlled
clinical trial comparing opioid-free versus opioid anaesthesia on postoperative
opioid-related adverse events after major or intermediate non-cardiac surgery.
AB - INTRODUCTION: Reducing opioid consumption during and after surgery has been
recommended for more than 10 years. Opioid-free anaesthesia (OFA) is a multimodal
anaesthesia associating hypnotics, NMDA antagonists, local anaesthetics, anti
inflammatory drugs and alpha-2 agonists. Proofs of the effect of OFA on reducing
opioid-related adverse effects after major or intermediate non-cardiac surgery
are still scarce. We hypothesised that the reduced opioid consumption allowed by
OFA compared with standard of care will be associated with a reduction of
postoperative opioid-related adverse events. METHODS/ANALYSIS: The POFA trial is
a prospective, randomised, parallel, single-blind, multicentre study of 400
patients undergoing elective intermediate or major non-cardiac surgery. Patients
will be randomly allocated to receive either a standard anaesthesia protocol or
an OFA. The primary outcome measure is the occurrence of a severe postoperative
opioid-related adverse event within the first 48 hours after extubation defined
as: postoperative hypoxaemia or postoperative ileus or postoperative cognitive
dysfunction. In addition, each component of the primary outcome measure will be
analysed separately. Data will be analysed on the intention-to-treat principle
and a per-protocol basis. ETHICS AND DISSEMINATION: The POFA trial has been
approved by an independent ethics committee for all study centres. Participant
recruitment begins in November 2017. Results will be published in international
peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT03316339; Pre
results.
PMID- 29961016
TI - Long-term sickness absence of 32 chronic conditions: a Danish register-based
longitudinal study with up to 17 years of follow-up.
AB - OBJECTIVES: Sickness absence has been used as a central indicator of work
disability, but has mainly been examined in single diseases, with limited follow
up time. This study identified the risk of long-term sickness absence (LTSA) of
32 chronic disease groups in the first year after diagnosis and the subsequent
years. SETTING: We identified chronic disease groups prevalent in the work force
(26 physical and 6 mental conditions) requiring all levels of care (primary,
secondary, tertiary), by national registers of diagnoses from all hospital visits
and prescribed medicine in Denmark from 1994 to 2011. PARTICIPANTS: A general
population sample within the working age range (18-59 years) was drawn by
Statistics Denmark. Participants not working before and during the follow-up
period were excluded. A total of 102 746 participants were included. PRIMARY AND
SECONDARY OUTCOME MEASURES: HRs of transitions from work to LTSA of each of the
chronic conditions were estimated in Cox proportional hazards models for repeated
events-distinguishing between risk within the first (<1 year) and subsequent
years of diagnosis (>=1 year) and an HR ratio (HRR): HR >=1 year divided by HR <1
year. RESULTS: Almost all the conditions were associated with significantly
increased risks of LTSA over time. The risks were generally more increased in men
than in women. Three main patterns of LTSA were identified across diseases:
strong decreases of LTSA from the first to subsequent years (eg, stroke in men <1
year: HR=7.55, 95% CI 6.45 to 8.85; >=1 year HR=1.43, 95% CI 1.20 to 1.74;
HRR=0.23). Moderate or small decreases in LTSA (HRR between 0.46 and 0.76). No
changes (HRR between 0.92 and 0.95) or increases in elevated risks of LTSA over
time (HRR between 1.02 and 1.16). CONCLUSIONS: The 32 chronic diseases were
associated with three different risk patterns of LTSA over time. These patterns
implicate different strategies for managing work disability over time.
PMID- 29961017
TI - Quality of life among individuals with rugby-related spinal cord injuries in
South Africa: a descriptive cross-sectional study.
AB - OBJECTIVES: Rugby-related spinal cord injuries (SCIs) are rare but life altering
and traumatic events. Little is known about the long-term consequences and
outcomes of players who have sustained these injuries. This study investigated
current quality of life (QoL) and factors associated with QoL, among individuals
with rugby-related SCI in South Africa, by using the International Classification
of Functioning, Disability and Health (ICF) framework. DESIGN: Descriptive cross
sectional study. SETTING: Rugby-related SCI population of South Africa, as
captured in the BokSmart/Chris Burger Petro Jackson Players' Fund database.
PARTICIPANTS: Ninety (n=90) of the 102 eligible players on the database agreed to
participate in the study. MAIN OUTCOME MEASURE: The relationship between QoL, as
measured with the WHO Quality of Life questionnaire (WHOQOL-BREF) and specific
independent variables (demographic information, level of independence and
participation in various activities and life roles) was investigated. Variables
that were significantly associated with QoL in bivariate analyses were included
in multiple linear regression analyses. RESULTS: The mean score and SD of the
WHOQOL-BREF was 15.1+/-2.3 arbitrary units. Participation (an ICF framework
construct) and income were significantly associated with overall QoL (p<0.001).
Participation was the only variable significantly associated with all QoL
subdomains (p<0.001). Additionally, number of health concerns, type of healthcare
(public vs private) and level of education were significantly associated with
various QoL domains (p<0.001). CONCLUSIONS: On average, these individuals with
rugby-related SCI presented with higher QoL scores than other comparable SCI
studies. However, lower levels of participation and income, certain levels of
education, increased health concerns and use of public healthcare were associated
with lower levels of QoL. Sporting bodies have a responsibility to optimise
player welfare, by acting on the modifiable factors associated with QoL.
PMID- 29961018
TI - Development and feasibility of a guided and tailored internet-based cognitive
behavioural intervention for kidney donors and kidney donor candidates.
AB - OBJECTIVES: Living donor kidney transplantation is currently the preferred
treatment for patients with end-stage renal disease. A subgroup of the kidney
donor population experiences adjustment problems during or after the donation
procedure (eg, anxiety or fatigue). There is a need for evidence-based
interventions that decrease donation-related difficulties before or after
donation. In the current study, a guided and tailored internet-based cognitive
behavioural therapy (ICBT) intervention for donors and donor candidates was
developed and the feasibility and perceived effectiveness were evaluated. DESIGN:
Pilot study including qualitative and quantitative research methods for
intervention development and evaluation. SETTING: Living kidney donor population
of two Dutch transplantation centres. PARTICIPANTS: Donors and healthcare
professionals participated in focus group interviews conducted to identify
intervention themes and to map attitudes towards internet-based interventions. In
a pilot feasibility study, 99 donors and donor candidates participated, of whom
38 completed the screening. Eight donors or donor candidates with a risk profile
(ie, impaired mental health-related quality of life (HRQoL)) received and
evaluated the intervention. INTERVENTIONS: A guided and tailored ICBT
intervention for donors and donor candidates was developed. Donation-related
treatment modules, assignments and psychoeducation were integrated within an
existing disease-generic ICBT intervention. OUTCOME MEASURES: HRQoL, anxiety and
depression were assessed before and after the ICBT intervention. Additional
questionnaires were included to identify specific problem areas of donor
functioning to tailor the ICBT intervention to the donor's needs. RESULTS:
Different intervention themes were derived from the focus group interviews (eg,
physical limitations, and donation-specific emotional and social-relational
problems). Participants were satisfied about the intervention content (7.7+/-0.8
on a 0-10 scale) and the therapeutic relationship (4.4+/-0.6 on a 1-5 scale), and
indicated an improvement on domains of their treatment goals (3.2+/-0.7 on a 1-4
scale). CONCLUSION: This study showed positive evaluations concerning both
feasibility and perceived effectiveness of the tailored ICBT intervention in
kidney donors and donor candidates, in line with previous studies using
comparable ICBT treatment protocols in other populations. Future research should
examine the possibilities of integrating the intervention into psychosocial care
for kidney donors.
PMID- 29961020
TI - What can make things better for parents when babies need abdominal surgery in
their first year of life? A qualitative interview study in the UK.
AB - OBJECTIVES: To understand the experiences of parents of infants who required
surgery early in life. To identify messages and training needs for the extended
clinical teams caring for these families-including paediatric surgeons,
neonatologists, nurses, obstetricians, midwives and sonographers. SETTING: UK
wide interview study, including England, Wales and Scotland. PARTICIPANTS: In
depth interviews were conducted with 44 parents who had a baby who underwent
early abdominal surgery. Conditions included those diagnosed antenatally (eg,
exomphalos, gastroschisis, congenital diaphragmatic hernia) or those which were
detected postnatally (eg, Hirschsprung's disease, necrotising enterocolitis).
Interviews were video and audio recorded and analysed using a modified grounded
theory approach. RESULTS: While some parents reported experiencing excellent
communication and felt they were listened to and involved by the care team, this
was not always the case. Dealing with large, complex medical and surgical teams
could result in conflicting messages, uncertainty and distress. Parents wanted
information but also described being overwhelmed and wanting to distance
themselves to maintain hope. Information and support from other parents in
hospital and online groups were highly valued. Of particular concern was support
when going home and caring for their baby after discharge; an open access policy
for readmission offered a helpful safety net. CONCLUSIONS: Listening to the
experience of parents provides rich data to enhance clinical understandings on
how to improve information and communication with parents, and ameliorate the
deep and lasting distress and anxiety that some parents feel when their infants
face early surgery. We suggest that the writings of Bourdieu could have resonance
in interpreting the experiences of parents as they enter the world of highly
technical neonatal medicine and surgery and the knowledge of the professionals
who work in these environments.
PMID- 29961019
TI - Conflict of interest among Italian medical oncologists: a national survey.
AB - OBJECTIVES: To assess Italian medical oncologists' opinion on the implications of
conflict of interest (COI) on medical education, care and research, and to
evaluate their direct financial relationships. DESIGN: National cross-sectional
survey conducted between March and April 2017 among Italian oncologists. SETTING:
Online survey sponsored by the Italian College of Medical Oncology Chiefs through
its website. PARTICIPANTS: Italian oncologists who filled out an anonymous
questionnaire including 19 items and individual and working characteristics. MAIN
OUTCOME MEASURE: The proportion of medical oncologists perceiving COI as an
outstanding issue and those receiving direct payments from industry. RESULTS:
There were 321 respondents, representing 13% of Italian tenured medical
oncologists. Overall, 62% declared direct payments from the pharmaceutical
industry in the last 3 years. Sixty-eight per cent felt the majority of Italian
oncologists have a COI with industry, but 59% suppose this is not greater than
that of other specialties. Eighty-two per cent consider that most oncology
education is supported by industry. More than 75% believe that current allocation
of industry budget on marketing and promotion rather than research and
development is unfair, but 75% consider it appropriate to receive travel and
lodging hospitality from industry. A median net profit margin of ?5000 per
patient enrolled in an industry trial was considered appropriate for the employee
institution. Sixty per cent agree to receive a personal fee for patients enrolled
in industry trials, but 79% state this should be reported in the informed
consent. Over 90% believe that scientific societies should publish a financial
report of industry support. Finally, 79% disagree to being a coauthor of an
article written by a medical writer when no substantial scientific contribution
is made. CONCLUSIONS: Among Italian oncologists COI is perceived as an important
issue influencing costs, education, care and science. A more rigorous policy on
COI should be implemented.
PMID- 29961021
TI - Using electronic health records to quantify and stratify the severity of type 2
diabetes in primary care in England: rationale and cohort study design.
AB - INTRODUCTION: The increasing prevalence of type 2 diabetes mellitus (T2DM)
presents a significant burden on affected individuals and healthcare systems
internationally. There is, however, no agreed validated measure to infer diabetes
severity from electronic health records (EHRs). We aim to quantify T2DM severity
and validate it using clinical adverse outcomes. METHODS AND ANALYSIS: Primary
care data from the Clinical Practice Research Datalink, linked hospitalisation
and mortality records between April 2007 and March 2017 for patients with T2DM in
England will be used to develop a clinical algorithm to grade T2DM severity. The
EHR-based algorithm will incorporate main risk factors (severity domains) for
adverse outcomes to stratify T2DM cohorts by baseline and longitudinal severity
scores. Provisionally, T2DM severity domains, identified through a systematic
review and expert opinion, are: diabetes duration, glycated haemoglobin,
microvascular complications, comorbidities and coprescribed treatments. Severity
scores will be developed by two approaches: (1) calculating a count score of
severity domains; (2) through hierarchical stratification of complications.
Regression models estimates will be used to calculate domains weights. Survival
analyses for the association between weighted severity scores and future outcomes
cardiovascular events, hospitalisation (diabetes-related, cardiovascular) and
mortality (diabetes-related, cardiovascular, all-cause mortality)-will be
performed as statistical validation. The proposed EHR-based approach will
quantify the T2DM severity for primary care performance management and inform the
methodology for measuring severity of other primary care-managed chronic
conditions. We anticipate that the developed algorithm will be a practical tool
for practitioners, aid clinical management decision-making, inform stratified
medicine, support future clinical trials and contribute to more effective service
planning and policy-making. ETHICS AND DISSEMINATION: The study protocol was
approved by the Independent Scientific Advisory Committee. Some data were
presented at the National Institute for Health Research School for Primary Care
Research Showcase, September 2017, Oxford, UK and the Diabetes UK Professional
Conference March 2018, London, UK. The study findings will be disseminated in
relevant academic conferences and peer-reviewed journals.
PMID- 29961022
TI - Mindful Self-Care and Resiliency (MSCR): protocol for a pilot trial of a brief
mindfulness intervention to promote occupational resilience in rural general
practitioners.
AB - INTRODUCTION: The Mindful Self-Care and Resiliency (MSCR) programme is a brief
psychosocial intervention designed to promote resilience among various
occupational groups. The intervention is based on the principles of mindfulness
and also incorporates an educational self-care component. The current paper
presents the protocol for a pilot study that will evaluate the effectiveness of
this programme among general practitioners working in rural Queensland,
Australia. METHODS AND ANALYSIS: We will measure the impact of the MSCR programme
on levels of employee resilience (Connor-Davidson Resilience Scale; State-Trait
Assessment of Resilience STARS), compassion satisfaction and compassion fatigue
(Professional Quality of Life Scale), self-compassion (Self-Compassion Scale) and
mood (Positive and Negative Affect Scale). We will also assess the impact of the
programme on job satisfaction (The Abridged Job in General Scale),
absenteeism/presenteeism (The WHO Health and Work Performance Questionnaire) and
general well-being (WHO Five Well-being Index). Repeated measures analysis of
variance will be used to analyse the impact of the intervention on the outcome
measures taken at pre, post, 1-month, 3-month and 6-month follow-ups. We will
conduct individual interviews with participants to gather data on the feasibility
and acceptability of the programme. Finally, we will conduct an initial cost
effectiveness analysis of the programme. ETHICS AND DISSEMINATION: Approval for
this study was obtained from the Curtin University Human Research ethics
committee and the study has been registered with the Australian Clinical Trials
Registry. Results will be published and presented at national and international
congresses. TRIAL REGISTRATION NUMBER: ACTRN12617001479392p; Pre-results.
PMID- 29961023
TI - Can inspiratory muscle training improve weaning outcomes in difficult to wean
patients? A protocol for a randomised controlled trial (IMweanT study).
AB - INTRODUCTION: Respiratory muscle dysfunction has been associated with failure to
wean from mechanical ventilation. It has therefore been hypothesised that these
patients might benefit from inspiratory muscle training (IMT). Evidence, however,
is thus far limited to data from small, single-centre studies with heterogeneity
in inclusion criteria, training modalities and outcomes. The aim of this study is
to evaluate the effects of a novel IMT method on weaning outcomes in selected
patients with weaning difficulties. METHODS: This study is designed as a double
blind, parallel-group, randomised controlled superiority trial with 1:1
allocation ratio. Patients with weaning difficulties will be randomly allocated
into either an IMT group (intervention) or a sham-IMT group (control).
Ninetypatients (45 in each group) will be needed to detect a 28% difference in
the proportion of weaning success between groups (estimated difference in primary
outcome based on previous studies) with a risk for type I error (alpha) of 5% and
statistical power (1-beta) of 80%. Patients will perform four sets of 6-10
breaths daily against an external load using a tapered flow resistive loading
device (POWERbreathe KH2, HaB International, UK). Training intensity in the
intervention group will be adjusted to the highest tolerable load. The control
group will train against a low resistance that will not be modified during the
training period. Training will becontinued until patients are successfully weaned
or for a maximum duration of 28 days. Pulmonary and respiratory muscle function,
weaning duration, duration of mechanical ventilation, ventilator-free days and
length of stay in the intensive care unit will be evaluated as secondary
outcomes. Chi2 tests and analysis of covariance with adjustments for baseline
values of respective outcomesas covariates will be used to compare results after
the intervention period between groups. ETHICS AND DISSEMINATION: Ethics approval
was obtained from the local ethical committee (Ethische Commissie Onderzoek UZ/KU
Leuven protocol ID: S60516). Results from this randomised controlled trial will
be presented at scientific meetings as abstracts for poster or oral presentations
and published in peerreviewed journals. TRIAL STATUS: Enrolment into the study
have started in August 2017. Data collection and data analysis are expected to be
completed in September 2021. TRIAL REGISTRATION NUMBER: NCT03240263.
PMID- 29961024
TI - Evaluation of published assessment tools for comorbidity in liver
transplantation: a systematic review protocol.
AB - INTRODUCTION: Liver transplantation is considered the best therapy option for end
stage liver disease. Different factors including recipient comorbidity at time of
transplantation are supposed to have substantial impact on outcomes. Although
several studies have focused on comorbidity assessment indices for liver
transplant recipients, there is no systematic review available on the
methodological details and prognostic accuracy of these instruments. The aim of
this study is to systematically review recipient comorbidity assessment indices
in the context of liver transplantation. METHODS AND ANALYSIS: PubMed, Embase,
Web of Science and PsyINFO databases will be searched. Studies describing, using
or evaluating specific assessment tools to predict the effect of comorbidity on
clinical outcomes after liver transplantation will be included. The selection
will be conducted independently by two reviewers. The study characteristics and
methodological information on published comorbidity assessment tools will be
extracted into a predefined structural table. This approach will be deployed to
systematically extract information on the validity, reliability and practical
feasibility of investigated comorbidity assessment tools for comparative
evaluation. Narrative information synthesis will be conducted, and additional
meta-analytical comparison will be performed, if appropriate. ETHICS AND
DISSEMINATION: All data are collected from published literature. Thus, formal
ethics review for the research is not required. The findings of this systematic
review will be published in a peer-reviewed journal and presented at relevant
conferences. The results of this systematic review will be highly relevant for
further research on prognostic models, clinical decision making and optimisation
of donor organ allocation. PROSPERO REGISTRATION NUMBER: CRD42017074609.
PMID- 29961025
TI - Facilitators and barriers to the effective implementation of the individual
maternal near-miss case reviews in low/middle-income countries: a systematic
review of qualitative studies.
AB - BACKGROUND: The maternal near-miss cases review (NMCR), a type of clinical audit,
proved to be effective in improving quality of care and decreasing maternal
mortality in low/middle-income countries (LMICs). However, challenges in its
implementation have been described. OBJECTIVES: Synthesising the evidence on
facilitators and barriers to the effective implementation of NMCR in LMICs.
DESIGN: Systematic review of qualitative studies. DATA SOURCES: MEDLINE, LILACS,
Global Health Library, SCI-EXPANDED, SSCI, Cochrane library and Embase were
searched in December 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
Qualitative studies exploring facilitators and/or barriers of implementing NMCR
in LMIC were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers
extracted data, performed thematic analysis and assessed risk of bias. RESULTS:
Out of 25 361 papers retrieved, 9 studies from Benin, Brazil, Burkina Faso, Cote
D'Ivoire, Ghana, Malawi, Morocco, Tanzania, Uganda could be included in the
review. The most frequently reported barriers to NMCR implementation were the
following: absence of national guidelines and local protocols; insufficient
training on how to perform the audit; lack of leadership, coordination,
monitoring and supervision; lack of resources and work overload; fear of blame
and punishment; poor knowledge of evidenced-based medicine; hierarchical
differences among staff and poor understating of the benefits of the NMCR. Major
facilitators to NMCR implementation included: good leadership and coordination;
training of all key staff; a good cultural environment; clear staff's perception
on the benefits of conducting audit; patient empowerment and the availability of
external support. CONCLUSIONS: In planning the NMCR implementation in LMICs,
policy-makers should consider actions to prevent and mitigate common challenges
to successful NMCR implementation. Future studies should aim at documenting
facilitators and barriers to NMCR outside the African Region.
PMID- 29961027
TI - Development of a research platform for children with arthrogryposis multiplex
congenita: study protocol for a pilot registry.
AB - INTRODUCTION: Arthrogryposis multiplex congenita (AMC) describes a heterogeneous
group of conditions with multiple congenital contractures. These conditions may
be attributed to genetic or other factors inducing decreased fetal movements,
including maternal and paternal factors. Discovering the underlying genetic
pathways has important repercussions for prevention, gene therapy and genetic
counselling. The current literature mainly consists of small-scale, single-site
studies, limiting comparability and pooling of findings across individual
studies. A pilot registry for children presenting with AMC is proposed to provide
the framework for a large-scale AMC registry. This registry will provide the
platform to support high-quality studies to inform the distribution, clinical
practice and genetics contributing to this group of conditions. METHODS AND
ANALYSIS: The registry will be piloted on 40 families of children from birth to
21 years of age presenting with AMC. Data will be collected on the child
(demographic and newborn variables), mother and father (demographic, lifestyle
habits and medical history). To promote standardised data collection, a manual of
operations will be developed. Descriptive statistics will be used to summarise
relevant data, regression analyses will be used to explore associations to
generate hypotheses regarding factors contributing to AMC. Qualitative analysis
will also be used to better describe the various phenotypes. ETHICS AND
DISSEMINATION: Ethics approval was obtained at the participating sites. The pilot
registry will provide the platform for multisite AMC registry that will generate
multiple research avenues to enhance current care and establish new therapies.
Following this pilot study, the participant selection criteria will be refined
and datasets will be expanded to include rehabilitation and surgical
interventions, and genetic sequencing. The best timing for the questionnaire
administration and frequency of follow-up prior to the implementation of a
multisite AMC registry will be determined.
PMID- 29961026
TI - Relationship between sociodemographic factors and selection into UK postgraduate
medical training programmes: a national cohort study.
AB - INTRODUCTION: Knowledge about allocation of doctors into postgraduate training
programmes is essential in terms of workforce planning, transparency and equity
issues. However, this is a rarely examined topic. To address this gap in the
literature, the current study examines the relationships between applicants'
sociodemographic characteristics and outcomes on the UK Foundation Training
selection process. METHODS: A longitudinal, cohort study of trainees who applied
for the first stage of UK postgraduate medical training in 2013-2014. We used UK
Medical Education Database (UKMED) to access linked data from different sources,
including medical school admissions, assessments and postgraduate training.
Multivariable ordinal regression analyses were used to predict the odds of
applicants being allocated to their preferred foundation schools. RESULTS:
Applicants allocated to their first-choice foundation school scored on average a
quarter of an SD above the average of all applicants in the sample. After
adjusting for Foundation Training application score, no statistically significant
effects were observed for gender, socioeconomic status (as determined by income
support) or whether applicants entered medical school as graduates or not.
Ethnicity and place of medical qualification were strong predictors of allocation
to preferred foundation school. Applicants who graduated from medical schools in
Wales, Scotland and Northern Ireland were 1.17 times, 3.33 times and 12.64 times
(respectively), the odds of applicants who graduated from a medical school in
England to be allocated to a foundation school of their choice. CONCLUSIONS: The
data provide supportive evidence for the fairness of the allocation process but
highlight some interesting findings relating to 'push-pull' factors in medical
careers decision-making. These findings should be considered when designing
postgraduate training policy.
PMID- 29961028
TI - Missing from the debate? A qualitative study exploring the role of communities
within interventions to address female genital mutilation in Europe.
AB - INTRODUCTION: Public attention on female genital mutilation (FGM) in diaspora
communities is increasing in Europe, as health and social welfare implications
become better understood. This study explored the role of potentially affected
communities within interventions to address FGM in Europe, examining current
practices, promising interventions and remaining gaps. METHODS: A qualitative
study design incorporated 18 individual key informant interviews and five
semistructured group interviews with policy-makers, service providers and
community representatives. Data were analysed thematically, guided by the
Scottish Government '4Ps' framework for addressing violence against women and
girls, that is, prevention, protection, provision of services and participation.
RESULTS: Participants emphasised both the importance of community participation
and the lack of consistent engagement by policy-makers and practitioners. All
indicated that communities had a key role, though most interventions focused on
awareness-raising rather than community empowerment, behaviour change or
influence on the design, delivery and/or evaluation of interventions.
CONCLUSIONS: Despite clear consensus around the need to engage, support and
empower potentially affected communities and several examples of meaningful
community participation in addressing FGM (eg, REPLACE, REPLACE 2, Ketenaapak,
Tackling FGM Initiative), the role of communities remains inconsistent and
further engagement efforts are necessary.
PMID- 29961029
TI - Death within 1 year among emergency medical admissions to Scottish hospitals:
incident cohort study.
AB - BACKGROUND: It is increasingly recognised that large numbers of hospital
inpatients have entered the last year of their lives. AIM: To establish the
likelihood of death within 12 months of admission to hospital; to examine the
influence on survival of a cancer diagnosis made within the previous 5 years; to
assess whether previous emergency admissions influenced mortality; and to compare
mortality with that of the wider Scottish population. DESIGN: Incident cohort
study. SETTING: 22 hospitals in Scotland. PARTICIPANTS: This study used routinely
collected data from 10 477 inpatients admitted as an emergency to medicine in 22
Scottish hospitals between 18 and 31 March 2015. These data were linked to
national death records and the Scottish Cancer Registry. PRIMARY OUTCOME
MEASURES: 1 year cohort mortality compared with that of the general Scottish
population. Patient factors correlating with higher risk of mortality were
identified using Cox regression. RESULTS: There were 2346 (22.4%) deaths in the
year following the census admission. Six hundred and ten patients died during
that admission (5.8% of all admissions and 26% of all deaths) while 1736 died
after the census admission (74% of all deaths). Malignant neoplasms (33.8%),
circulatory diseases (22.5%) and respiratory disease (17.9%) accounted for almost
three-quarters of all deaths. Mortality rose steeply with age and was five times
higher at 1 year for patients aged 85 years and over compared with those who were
under 60 years of age (41.9%vs7.9%) (p<0.001). Patients with cancer had a higher
mortality rate than patients without a cancer diagnosis (55.6%vs16.6%) (p<0.001).
Mortality was higher among patients with one or more emergency medical admissions
in the previous year (30.1% v 15.1%) (p<0.001). Age/sex-standardised mortality
was 110.4 (95% CI 104.4 to 116.5) for the cohort and 11.7 (95% CI 11.6 to 11.8)
for the Scottish population, a 9.4-fold increase in risk. CONCLUSION: These data
may help identify groups of patients admitted to hospital as medical emergencies
who are at greatest risk of dying not only during admission but also in the
following 12 months.
PMID- 29961030
TI - Prevalence of dyslipidaemia and awareness of blood cholesterol levels among
community-living people: results from the Longevity check-up 7+ (Lookup 7+) cross
sectional survey.
AB - OBJECTIVE: The aim of the present study was to investigate the prevalence of
abnormal cholesterol levels and to explore awareness of cholesterol values in an
unselected sample of community-living adults. DESIGN: Cross-sectional survey.
SETTING: Exhibitions, malls and health promotion campaigns across Italy.
PARTICIPANTS: 3535 community dwellers aged 18-98 years were enrolled between
September 2016 and June 2017. Analyses were conducted in 3040 participants, after
excluding 495 enrolees on cholesterol-lowering medications. MAIN OUTCOME
MEASURES: Total blood cholesterol levels and awareness of cholesterol values.
RESULTS: Abnormal blood cholesterol values were found in 1961 (64.5%) of
participants with no differences between genders (p=0.06). Among those who
believed they had normal cholesterol levels, only 48% had values below 200 mg/dL.
More than 40% had cholesterol values between 200 and 240 mg/dL, and around 10%
had values >240 mg/dL. More than one-third of participants had not measured
cholesterol in the last year. Among them, only 36% had normal cholesterol levels.
CONCLUSIONS: Abnormal blood cholesterol is highly prevalent in our sample of
Italian community dwellers, with less than half of participants being aware of
their cholesterol levels.
PMID- 29961031
TI - Physiotherapy and Anterior Resection Syndrome (PARiS) trial: feasibility study
protocol.
AB - INTRODUCTION: Rectal cancer affects more than 600 patients per year in Wales,
with a 5-year survival rate of around 60%. A recent report demonstrated that 19%
of patients with bowel cancer had difficulty controlling their bowels after
surgery, and these patients were twice as likely to report lower quality of life
than those who had control. Nearly all patients will experience bowel dysfunction
initially following surgery and up to 25% will experience severe bowel
dysfunction on a long-term basis. The aim of this study is to test the
feasibility of introducing a simple intervention in an attempt to improve bowel
function following surgery for rectal cancer. We propose the introduction of an
educational session from specialist nurses and physiotherapists prior to surgery
and a subsequent physiotherapy programme for 3 months to teach patients how to
strengthen their pelvic floor. METHODS AND ANALYSIS: All patients with rectal
cancer planned to receive an anterior resection will be approached for the study.
The study will take place in three centres over 12 months, and we expect to
recruit 40 patients. The primary outcome measure is the proportion of eligible
patients approached who consent to and attend the educational session. The
secondary outcomes include patient compliance to the pelvic floor rehabilitation
programme (assessed by patient paper or electronic diary), the acceptability of
the intervention to the patient (assessed using qualitative interviews) and
preoperative and postoperative pelvic floor tone (assessed using the Oxford
Grading System and the International Continence Society Grading System), patient
bowel function and patient quality of life (assessed using validated
questionnaires). ETHICS AND DISSEMINATION: Ethics approval was granted. This
feasibility study is in progress. If patients find the intervention acceptable,
the next stage would be a trial comparing outcomes after anterior resection in
those who have and do not have physiotherapy. TRIAL REGISTRATION NUMBER:
ISRCTN77383505; Pre-results.
PMID- 29961032
TI - SMARTphone and social media-based Cardiac Rehabilitation and Secondary Prevention
(SMART-CR/SP) for patients with coronary heart disease in China: a randomised
controlled trial protocol.
AB - INTRODUCTION: The burden of cardiovascular disease (CVD) is rapidly increasing in
developing countries, however access to cardiac rehabilitation and secondary
prevention (CR/SP) in these countries is limited. Alternative delivery models
that are low-cost and easy to access are urgently needed to address this service
gap. The objective of this study is to investigate whether a smartphone and
social media-based (WeChat) home CR/SP programme can facilitate risk factor
monitoring and modification to improve disease self-management and health
outcomes in patients with coronary heart disease (CHD), after percutaneous
coronary intervention (PCI) therapy. METHODS AND ANALYSIS: We propose a single
blind, randomised controlled trial of 300 patients post-PCI with follow-up over
12 months. The intervention group will receive a smartphone-based and WeChat
based CR/SP programme providing education and support for risk factor monitoring
and modification. SMART-CR/SP incorporates core components of modern CR/SP:
physical activity tracking with interactive feedback and goal setting; education
modules addressing CHD understanding and self-management; remote blood pressure
monitoring and strategies to improve medication adherence. Furthermore, a
dedicated data portal and a CR/SP coach will facilitate individualised
supervision and counselling. The control group will receive usual care but no
formal CR/SP programme. The primary outcome is change in exercise capacity
measured by 6 minute walk test distance. Secondary outcomes include knowledge and
awareness of CHD, risk factor status, medication adherence, psychological well
being and quality of life, major cardiovascular events, re-hospitalisations and
all-cause mortality. To assess the feasibility and patients' acceptance of the
intervention, a process evaluation will be performed at the conclusion of the
study. ETHICS AND DISSEMINATION: Ethics approval was granted by both the Human
Research Ethics Committee of Fudan University Zhongshan Hospital (HREC B2016-058)
and Curtin University Human Research Ethics Office (HRE2016-0120). Results will
be disseminated via peer-reviewed publications and presentations at conferences.
CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-INR-16009598; Pre-results.
PMID- 29961033
TI - How do iLead? Validation of a scale measuring active and passive implementation
leadership in Swedish healthcare.
AB - OBJECTIVES: This study aims to describe the creation of a scale-the iLead scale
through adaptations of existing domain-specific scales that measure active and
passive implementation leadership, and to describe the psychometric properties of
this scale. METHODS: Data collected from a leadership intervention were used in
this validation study. Respondents were 336 healthcare professionals (90% female
and 10% male; mean age 47 years) whose first-line and second-line managers
participated in the intervention. The data were collected in the Stockholm
regional healthcare organisation that offer primary, psychiatric, rehabilitation
and acute hospital care, among other areas. The items for measuring
implementation leadership were based on existent research and the full-range
leadership model. Confirmatory factor analysis was performed to evaluate the
dimensionality of the scale, followed by tests for reliability and convergent,
discriminant and criterion-related validity using correlations and multilevel
regression analyses. RESULTS: The final scale consists of 16 items clustered into
four subscales representing active implementation leadership, and one scale
signifying passive implementation leadership. Findings showed that the
hypothesised model had an acceptable model fit (chi2(99)=382.864**, Comparative
Fit Index=0.935, Tucker-Lewis Index=0.911, root mean square error of
approximation=0.059). The internal consistency and convergent, discriminant and
criterion-related validity were all satisfactory. CONCLUSIONS: The iLead scale is
a valid measure of implementation leadership and is a tool for understanding how
active and passive leader behaviours influence an implementation process. This
brief scale may be particularly valuable to apply in training focusing on
facilitating implementation, and in evaluating leader training. Moreover, the
scale can be useful in evaluating various leader behaviours associated with
implementation success or failure.
PMID- 29961034
TI - Development of a toolkit to enhance care processes for people with a long-term
neurological condition: a qualitative descriptive study.
AB - OBJECTIVE: To (A) explore perspectives of people with a long-term neurological
condition, and of their family, clinicians and other stakeholders on three key
processes: two-way communication, self-management and coordination of long-term
care; and (B) use these data to develop a 'Living Well Toolkit', a structural
support aiming to enhance the quality of these care processes. DESIGN: This
qualitative descriptive study drew on the principles of participatory research.
Data from interviews and focus groups with participants (n=25) recruited from
five hospital, rehabilitation and community settings in New Zealand were analysed
using conventional content analysis. Consultation with a knowledge-user group
(n=4) and an implementation champion group (n=4) provided additional operational
knowledge important to toolkit development and its integration into clinical
practice. RESULTS: Four main, and one overarching, themes were constructed: (1)
tailoring care:referring to getting to know the person and their individual
circumstances; (2) involving others: representing the importance of negotiating
the involvement of others in the person's long-term management process; (3)
exchanging knowledge: referring to acknowledging patient expertise; and (4)
enabling: highlighting the importance of empowering relationships and processes.
The overarching theme was: assume nothing. These themes informed the development
of a toolkit comprising of two parts: one to support the person with the long
term neurological condition, and one targeted at clinicians to guide interaction
and support their engagement with patients. CONCLUSION: Perspectives of
healthcare users, clinicians and other stakeholders were fundamental to the
development of the Living Well Toolkit. The findings were used to frame toolkit
specifications and highlighted potential operational issues that could prove key
to its success. Further research to evaluate its use is now underway.
PMID- 29961035
TI - Is atrial fibrillation a risk factor for in-hospital cardiac arrest?: a Swedish
retrospective cohort study.
AB - INTRODUCTION: Atrial fibrillation (AF) is associated with increased morbidity and
mortality. Recent findings suggest that AF is also associated with out-of
hospital cardiac arrest. However, whether that association can be generalised to
in-hospital cardiac arrests (IHCAs) is still unknown. AIMS: To examine whether
there is a stronger association with IHCA among hospitalised patients with AF
compared with patients without AF. MATERIALS AND METHODS: All adult patients
admitted to the Karolinska University Hospital, Stockholm, Sweden during 2014
2015 were included. Data were drawn from their medical file and matched against
the Swedish Registry for Cardiopulmonary Resuscitation. Patients who were
documented as ever having the International Classification of Diseases, 10th
revision code I48 prior to the current hospitalisation were categorised to the AF
group and the remaining were categorised to the non-AF group. The primary outcome
was occurrence of an IHCA. RESULTS: In all, 102 416 patients were included. Among
these, 10% had been diagnosed with AF and <1% (n=326) suffered from an IHCA, only
42 (13%) had a VF/VT. In a multivariable model adjusting for sex, age,
CharlsonComorbidity Index score and whether the patients had been admitted
electively or urgently, having AF was significantly associated with IHCA (OR
1.760; 95% CI 1.356 to 2.269; p<0.001). CONCLUSIONS: Within this observational
cohort study, patients with AF had a stronger association with IHCA than patients
without AF. AF might be an independent risk factor for IHCA.
PMID- 29961036
TI - How do care home staff understand, manage and respond to agitation in people with
dementia? A qualitative study.
AB - OBJECTIVES: Little is known about how care home staff understand and respond to
distress in residents living with dementia labelled as agitation. The aim of this
study was to describe how care home staff understand and respond to agitation and
the factors that determine how it is managed. DESIGN: We conducted a qualitative
thematic analysis. SETTING: We recruited staff from six care homes in South East
England including residential and nursing homes of differing sizes run by both
the private and charity sector and located in urban and rural areas.
PARTICIPANTS: We interviewed 25 care home staff using purposive sampling to
include staff of either sex, differing age, ethnicity, nationality and with
different roles and experience. RESULTS: We identified four overarching themes:
(1) behaviours expressing unmet need; (2) staff emotional responses to agitation;
(3) understanding the individual helps and (4) constraints on staff responses.
Staff struggled with the paradox of trying to connect with the personhood of
residents while seeing the person as separate to and, therefore, not responsible
for their behaviours. Staff often felt powerless, frightened and overwhelmed, and
their responses were constrained by care home structures, processes and a culture
of fear and scrutiny. CONCLUSIONS: Responding to agitation expressed by residents
was not a linear process and staff faced tensions and dilemmas in deciding how to
respond, especially when initial strategies were unsuccessful or when attempts to
respond to residents' needs were inhibited by structural and procedural
constraints in the care home. Future trials of psychosocial interventions should
support staff to identify and respond to residents' unmet needs and include how
staff can look after themselves.
PMID- 29961037
TI - Intra-articular botulinum toxin A for base-of-thumb osteoarthritis: protocol for
a randomised trial (RHIBOT).
AB - INTRODUCTION: Recent studies have suggested that intra-articular injection of
botulinum toxin A (BTA) may have analgesic effects in degenerative joint
diseases. We aim to assess the efficacy of intra-articular injection of BTA
associated with splinting in patients with trapeziometacarpal osteoarthritis (TMC
OA). METHODS AND ANALYSIS: We will conduct a randomised double-blind controlled
trial. Overall, 60 individuals with TMC OA fulfilling adapted 1990 American
College of Rheumatology criteria for hand OA will be recruited in one tertiary
care centre in France and randomised to receive splinting + a single ultrasound
guided injection in the TMC joint of 50 Allergan Units of BTA resuspended in 1 mL
saline or splinting +1 mL saline. Randomisation will be centralised. The
allocation ratio will be 1:1. The primary outcome will be the mean change from
baseline in base-of-thumb pain on a self-administered 11-point Numeric Rating
Scale in 10-point increments at 3 months after injection. Secondary outcomes will
be the mean change in base-of-thumb pain at 1 and 6 months, mean change in hand
specific activity limitations assessed by the self-administered Cochin Hand
Function Scale, proportion of responders assessed by the Osteoarthritis Research
Society International -Outcome Measures in Rheumatology (OMERACT) criteria and
consumption of analgesics and non-steroidal anti-inflammatory drugs assessed by a
self-administered 4-class scale at 3 and 6 months. Cointerventions will be
allowed in both groups and will be self-reported. Adverse events will be recorded
at 3 and 6 months. Participants, care providers and statisticians will be blinded
to the allocated treatment. ETHICS AND DISSEMINATION: The RHIBOT trial has been
authorised by the Agence Nationale de Securite du Medicament and approved by the
Comite de Protection des Personnes de Tours Ouest-1. The findings of the study
will be disseminated in peer-reviewed journals and at conferences. If the results
are positive, intra-articular BTA could be an efficient and safe complementary
therapeutic option for patients with TMC OA. DATE AND VERSION IDENTIFIER OF THE
PROTOCOL: 8 January 2018, V. 2.0. TRIAL REGISTRATION NUMBER: NCT03187626; Pre
results.
PMID- 29961038
TI - Do frailty measures improve prediction of mortality and morbidity following
transcatheter aortic valve implantation? An analysis of the UK TAVI registry.
AB - OBJECTIVES: Previous studies indicate frailty to be associated with poor outcomes
following transcatheter aortic valve implantation (TAVI), but there is limited
evidence from multicentre registries. The aim was to investigate the independent
association of frailty with TAVI outcomes, and the prognostic utility of adding
frailty into existing clinical prediction models (CPMs). DESIGN: The UK TAVI
registry incorporated three frailty measures since 2013: Canadian Study of Health
and Ageing, KATZ and poor mobility. We investigated the associations between
these frailty measures with short-term and long-term outcomes, using logistic
regression to estimate multivariable adjusted ORs, and Cox proportional hazards
models to explore long-term survival. We compared the predictive performance of
existing TAVI CPMs before and after updating them to include each frailty
measure. SETTING: All patients who underwent a TAVI procedure in England or Wales
between 2013 and 2014. PARTICIPANTS: 2624 TAVI procedures were analysed in this
study. PRIMARY AND SECONDARY OUTCOMES: The primary endpoints in this study were
30-day mortality and long-term survival. The Valve Academic Research Consortium
(VARC)-2 composite early safety endpoint was considered as a secondary outcome.
RESULTS: KATZ <6 (OR 2.10, 95% CI 1.39 to 3.15) and poor mobility (OR 2.15, 95%
CI 1.41 to 3.28) predicted 30-day mortality after multivariable adjustment. All
frailty measures were associated with increased odds of the VARC-2 composite
early safety endpoint. We observed a significant increase in the area under the
receiver operating characteristic curves by approximately 5% after adding KATZ <6
or poor mobility into the TAVI CPMs. Risk stratification agreement was
significantly improved by the addition of each frailty measure, with an increase
in intraclass correlation coefficient of between 0.15 and 0.31. CONCLUSION:
Frailty was associated with worse outcomes following TAVI, and incorporating
frailty metrics significantly improved the predictive performance of existing
CPMs. Physician-estimated frailty measures could aid TAVI risk stratification,
until more objective scales are routinely collected.
PMID- 29961039
TI - Effects of high-intensity interval training on vascular function in breast cancer
survivors undergoing anthracycline chemotherapy: design of a pilot study.
AB - INTRODUCTION: Cardiovascular disease (CVD) mortality is higher among breast
cancer survivors (BCS) who receive chemotherapy compared with those not receiving
chemotherapy. Anthracycline chemotherapy is of particular concern due to
anthracycline-related impairment of vascular endothelial cells and dysregulation
of the extracellular matrix. One strategy proven to offset these impairments is a
form of exercise known as high-intensity interval training (HIIT). HIIT improves
endothelial function in non-cancer populations by decreasing oxidative stress,
the main contributor to anthracycline-induced vascular dysfunction. The purpose
of this pilot study is to assess the feasibility of an 8-week HIIT, as well as
the HIIT effects on endothelial function and extracellular matrix remodelling, in
BCS undergoing anthracycline chemotherapy. METHODS AND ANALYSIS: Thirty BCS are
randomised to either HIIT, an 8-week HIIT intervention occurring three times per
week (seven alternating bouts of 90% of peak power output followed by 10% peak
power output), or delayed group (DEL). Feasibility of HIIT is assessed by (1) the
percentage of completed exercise sessions and (2) the number of minutes of
exercise completed over the course of the study. Vascular function is assessed
using brachial artery flow-mediated dilation and carotid intima media thickness.
Extracellular matrix remodelling is assessed by the level of matrix
metalloproteinases in the plasma. A repeated-measures analysis of covariance
model will be performed with group (HIIT and DEL group) and time (pre/post
assessment) as independent factors. We hypothesise that HIIT will be feasible in
BCS undergoing anthracycline chemotherapy, and that HIIT will improve endothelial
function and extracellular matrix remodelling, compared with the DEL group.
Success of this study will provide evidence of feasibility and efficacy to
support a larger definitive trial which will impact cancer survivorship by
decreasing anthracycline-induced vascular dysfunction, thereby benefiting
cardiovascular markers that are related to CVD risk. ETHICS AND DISSEMINATION:
This trial was approved by the University of Southern California Institutional
Review Board (HS-15-00227). TRIAL REGISTRATION NUMBER: NCT02454777; Pre-results.
PMID- 29961040
TI - Does the architectural layout of a NICU affect alarm pressure? A comparative
clinical audit of a single-family room and an open bay area NICU using a
retrospective study design.
AB - OBJECTIVES: To determine differences in alarm pressure between two otherwise
comparable neonatal intensive care units (NICUs) differing in architectural
layout-one of a single-family room (SFR) design and the other of an open bay area
(OBA) design. DESIGN: Retrospective audit of more than 2000 patient days from
each NICU cataloguing the differences in the number and duration of alarms for
critical and alerting alarms, as well as the interaction of clinicians with the
patient monitor. SETTING: Two level 3 NICUs. RESULTS: A total of more than 150
000 critical and 1.2 million alerting alarms were acquired from the two NICUs.
The number of audible alarms and the associated noise pollution varied
considerably with the OBA NICU generating 44% more alarms per infant per day even
though the SFR NICU generated 2.5 as many critical desaturation alarms per infant
per day. CONCLUSION: Differences in the architectural layout of NICUs and the
consequent differences in delays, thresholds and distribution systems for alarms
are associated with differences in alarm pressure.
PMID- 29961041
TI - Psychometric evaluation of an interview-administered version of the Kessler 10
item questionnaire (K10) for measuring psychological distress in rural
Bangladesh.
AB - OBJECTIVE: The aim of this study was to translate, adapt and validate the Kessler
10-item questionnaire (K10) for measuring psychological distress in rural
Bangladesh. DESIGN: Cohort study. SETTING: Narail district, Bangladesh.
PARTICIPANTS: A random sample of 2425 adults of age 18-90 years was recruited.
OUTCOME MEASURE: Validation of the K10 was the major outcome. Sociodemographic
factors were measured to assess if the K10 needed adjustment for factors such as
age or gender. The Rasch measurement model was used for the validation, and RUMM
2030 and SPSS V.24 software were used for analyses. RESULTS: Initial inspection
of the total sample showed poor overall fit. A sample size of 300, which is more
satiated for Rasch analysis, also showed poor overall fit, as indicated by a
significant item-trait interaction (chi2= 262.27, df=40, p<0.001) and item fit
residual values (mean=-0.25, SD=2.49). Of 10 items, five items were disordered
thresholds, and seven items showed misfit, suggesting problems with the response
format and items. After removing three items ('feel tired', 'depressed' and
'worthless') and changing the Likert scale categories from five to four
categories, the remaining seven items showed ordered threshold. A revised seven
item scale has shown adequate internal consistency, with no evidence of
multidimensionality, no differential item functioning on age and gender, and no
signs of local dependency. CONCLUSIONS: Analysis of the psychometric validity of
K10 using the Rasch model showed that 10 items are not appropriate for measuring
psychological distress in rural Bangladesh. A modified version of seven items
(K7) with four response categories would provide a psychometrically more robust
scale than the original K10. The study findings suggest repeating the K7 version
in other remote areas for further validation can substantiate an efficient
screening tool for measuring psychological distress among the general Bangladeshi
population.
PMID- 29961042
TI - Hospitalisation and mortality outcomes of patients with comorbid COPD and heart
failure: a systematic review protocol.
AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and heart failure (HF)
often coexist in patients. Many studies have explored the short-term and long
term outcomes of patients with comorbid COPD and HF; however, there have been
discrepancies in their findings. METHODS AND ANALYSIS: In this systematic review,
MEDLINE and Embase will be searched using a prespecified search strategy.
Randomised controlled trials and studies conducted in the general population that
employ analytical or descriptive (longitudinal or case-control) study designs
that report odds ratios (ORs), hazard ratios (HRs), or risk ratios (RRs) of
mortality or hospitalisation, comparing patients with comorbid COPD and HF with
patients with just COPD, will be selected. Screening by title and abstract, then
full-text screening will be conducted by two reviewers. The Population, Exposure,
Comparator, Outcomes, Study (PECOS) characteristics framework will be used to
systemise the data extraction from selected studies. Study quality will be
assessed using an adapted version of the Newcastle-Ottawa risk of bias tool. Data
extraction and the risk of bias will also be conducted by two reviewers. Given
sufficient homogeneity of selected studies, a meta-analysis will be conducted.
Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)
criteria will be used to assess the quality of cumulative evidence.
DISSEMINATION: With this review, we hope to improve the understanding of clinical
outcomes of patients with comorbid COPD and HF. We intend to publish the results
of our review in a peer-reviewed journal and to present our findings at national
and international meetings and conferences. PROSPERO REGISTRATION NUMBER:
CRD42018089534.
PMID- 29961043
TI - The impact of financial incentives to improve quality indicators in patients with
diabetes in Swiss primary care: a protocol for a cluster randomised controlled
trial.
AB - INTRODUCTION: There is only limited and conflicting evidence on the effectiveness
of Pay-for-Performance (P4P) programmes, although they might have the potential
to improve guideline adherence and quality of care. We therefore aim to test a
P4P intervention in Swiss primary care practices focusing on quality indicators
(QI) achievement in the treatment of patients with diabetes. METHODS AND
ANALYSIS: This is a cluster-randomised, two-armed intervention study with the
primary care practice as unit of randomisation. The control group will receive
bimonthly feedback reports containing last data of blood pressure and glycated
haemoglobin (HbA1c) measurements. The intervention group will additionally be
informed about a financial incentive for each percentage point improved in QI
achievement. Primary outcomes are differences in process (measurement of HbA1c)
and clinical QI (blood pressure control) between the two groups. Furthermore, we
investigate the effect on non-incentivised QIs and on sustainability of the
financial incentives. Swiss primary care practices participating in the FIRE
(Family Medicine ICPC Research using Electronic Medical Record) research network
are eligible for participation. The FIRE database consists of anonymised
structured medical routine data from Swiss primary care practices. According to
power calculations, 70 of the general practitioners contributing to the database
will be randomised in either of the groups. ETHICS AND DISSEMINATION: According
to the Local Ethics Committee of the Canton of Zurich, the project does not fall
under the scope of the law on human research and therefore no ethical consent is
necessary. Results will be published in a peer-reviewed journal. TRIAL
REGISTRATION NUMBER: ISRCTN13305645; Pre-results.
PMID- 29961044
TI - Child Labor Hazard on Mental Health: Evidence from Brazil.
AB - BACKGROUND: Child labor has been usually claimed to produce negative effects on
health. However, most of the studies that investigated this hypothesis examined
only its impact on child laborers' physical health. This study formulates the
hypothesis that child labor may have an impact on the mental health of these
individuals. AIMS OF STUDY: The aim of this study was to investigate the risk of
child laborers to develop symptoms of depression in adulthood and to examine the
role of physical and mental health of the family members on their risk of
developing depression. DATA AND METHODS: We used the 2008 National Household
Sample Survey (PNAD, Pesquisa Nacional por Amostra de Domicilios) and its special
supplements to estimate probit models. RESULTS: Individuals who started working
between the age group of 15-17 have about 0.6 percentage points lesser risk of
developing depression as compared to those who started working between the age
group of 10-14. Further reduction of this risk was observed for the age groups of
18-19 and 20-24. No statistical evidence was found regarding older age groups.
Individuals with a mother with depression have about 3.2 percentage points higher
risk of presenting symptoms of depression. Chronic physical illness in mothers
increases the risk of depression in child laborers by 0.3 percentage points.
DISCUSSION AND CONCLUSION: Our study supports the hypothesis that work during
childhood increases the risk of developing depression in adulthood. Family mental
health status and chronic physical illness play a substantial role in the risk
that child laborers have to develop depression. IMPLICATIONS FOR HEALTH POLICIES:
The results of the study indicate the need of basic mental health services aimed
to the assessment and care for child laborers who withdraw from work, with the
aim of reducing the risk of depression in adulthood. The results underline also
the importance of mental health assessment and care for those children with a
family member with depression or chronic physical illness.
PMID- 29961045
TI - Cost-effectiveness Analysis of a Stepped, Collaborative and Coordinated Health
Care Network for Patients with Somatoform Disorders (Sofu-Net).
AB - BACKGROUND: Somatoform disorders are highly prevalent mental disorders causing
impairment and large economic burden. In order to improve the diagnosis and
management of affected patients, a health care network for somatoform disorders
(Sofu-Net) was implemented in primary care. AIMS OF THE STUDY: The aim of the
study was to determine the cost-effectiveness of a stepped, collaborative and
coordinated health care network for somatoform and functional disorders (Sofu
Net) compared with regular primary care physician (PCP) practices in German
primary care from a societal perspective. METHODS: This study was part of a 6
month controlled, prospective, non-randomized, observer-blinded cluster cohort
trial. Participants were recruited from 33 PCP practices in Hamburg, Germany. The
health care network was a collaboration of PCPs, psychotherapists, inpatient
clinics and a specialized outpatient clinic. Participants in the control group
received usual care. A cost-effectiveness analysis, using treatment response as
measure of effectiveness, was performed. Uncertainty in cost-effectiveness was
analyzed using cost-effectiveness acceptability curves. RESULTS: In total, n=218
patients (n=119 patients in the intervention group and n=99 patients in the
control group) were included in the study. At 6 months, patients within the Sofu
Net group did not differ significantly from the control group with regard to
costs (533; standard error 941) and treatment response (--10.3%). For Sofu-Net,
the probability of being cost-effective at a willingness-to-pay (WTP) of 10,000
per additional response to treatment was only 31%. DISCUSSION: Sofu-Net is
unlikely to be cost-effective. Even for high WTP, the probability of cost
effectiveness was low. The results were robust to variation of costs included in
the analysis as well as when only complete cases were included in the analysis.
The most important limitations of the study were that randomization could not be
established at patient level and at practice level and that the study design did
not allow measurement of costs at baseline. CONCLUSION: Patients with severe
somatic symptoms did not benefit from the health care network. Sofu-Net might
have reduced costs in patients with moderate somatic symptoms. IMPLICATIONS FOR
FURTHER RESEARCH: Owing to the limitations and due to a short follow-up of this
study, further cost-effectiveness analyses with high methodological quality and a
follow-up of at least one year are needed in order to produce results that are
more reliable.
PMID- 29961046
TI - A Cost-effectiveness Study of the Impact of the Affordable Care Act on Depression
Outcomes in the United States.
AB - OBJECTIVE: Two separate changes in insurance regulation have altered mental
health delivery to Americans: (i) the Mental Health Parity and Addiction Equity
Act (MHPA 2008) and (ii) the Patient Protection and Affordable Care Act (ACA
2010). This study aims to model and provide estimates for the costs and effects
of depression that are impacted by these regulations. METHOD: Literature exists
on the effectiveness of insurance coverage in reducing the prevalence, the costs
of treatment and lost productivity time, as well as the health related quality of
life (HRQL) associated with depression. Data from this literature is employed in
a Markov model to obtain costs and effects associated with depression under both
the MHPA and the ACA regulations as compared to without either one. RESULTS: The
implementation of these regulations may reduce the per capita lifetime costs of
depression treatment and lost productivity by USD 215 and enhance life expectancy
by 0.01 Quality Adjusted Life Years (QALY) per capita. CONCLUSIONS: If the
savings of these regulations are expanded over the entire cohort of Americans
adults, the potential cost savings from treated depression are estimated at USD
47.30 billion in addition to 2.2 million QALYs saved.
PMID- 29961047
TI - Measuring Efficiency at the Interface of Behavioral and Physical Health Care.
AB - BACKGROUND: Measures of efficiency in healthcare delivery, particularly between
different parts of the healthcare system could potentially improve health
resource utilization. We use a typology adapted from the Agency for Healthcare
Research and Quality to characterize current measures described in the literature
by stakeholder perspective (payer, provider, patient, policy-maker), type of
output (reduced utilization or improved outcomes) and input (physical, financial
or both). AIMS OF THE STUDY: To systematically describe measures of healthcare
efficiency at the interface of behavioral and physical healthcare and identify
gaps in the literature base that could form the basis for further measure
development. METHODS: We searched the Medline database for studies published in
English in the last ten years with the terms 'efficiency', 'inefficiency',
'productivity', 'cost' or 'QALY' and 'mental' or 'behavioral' in the title or
abstract. Studies on healthcare resource utilization, costs of care, or broader
healthcare benefits to society, related to the provision of behavioral health
care in physical health care settings or to people with physical health
conditions or vice versa were included. RESULTS: 85 of 6,454 studies met
inclusion criteria. These 85 studies described 126 measures of efficiency. 100 of
these measured efficiency according to the perspective of the purchaser or
provider, whilst 13 each considered efficiency from the perspective of society or
the consumer. Most measures counted physical resources (such as numbers of
therapy sessions) rather than the costs of these resources as inputs. Three times
as many measures (95) considered service outputs as did quality outcomes (31).
DISCUSSION: Measuring efficiency at the interface of behavioral and physical care
is particularly difficult due to the number of relevant stakeholders involved,
ambiguity over the definition of efficiency and the complexity of providing care
for people with multimorbidity. Current measures at this interface concentrate on
a limited range of outcomes. LIMITATIONS: We only searched one database and did
not review the gray literature, nor solicit a call for relevant but unpublished
work. We did not assess the methodological quality of the studies identified.
IMPLICATION FOR HEALTH CARE PROVISION AND USE: Most measures of healthcare
efficiency are currently viewed from the perspective of payers and providers,
with very few studies addressing the benefits of healthcare to society or the
individual interest of the consumer. One way this imbalance could be addressed is
through much stronger involvement of consumers in measurement-development, for
example, by an expansion in patient-reported outcome measures in assessing
quality of care. IMPLICATIONS FOR HEALTH POLICIES: Integrating behavioral and
physical care is a major area of implementation as health systems in high income
countries move from volume to value based care delivery. Measuring efficiency at
this interface has the potential to incentivize and also evaluate integration
efforts. IMPLICATIONS FOR FURTHER RESEARCH: There has been only one previous
systematic review of efficiency measurement and none at the interface of
behavioral and physical care. We identify gaps in the evidence base for
efficiency measurement which could inform further research and measurement
development.
PMID- 29961048
TI - The Influence of Rearing on Behavior, Brain Monoamines, and Gene Expression in
Three-Spined Sticklebacks.
AB - The causes of individual variation in behavior are often not well understood, and
potential underlying mechanisms include both intrinsic and extrinsic factors,
such as early environmental, physiological, and genetic differences. In an
exploratory laboratory study, we raised three-spined sticklebacks (Gasterosteus
aculeatus) under 4 different environmental conditions (simulated predator
environment, complex environment, variable social environment, and control). We
investigated how these manipulations related to behavior, brain physiology, and
gene expression later in life, with focus on brain dopamine and serotonin levels,
turnover rates, and gene expression. The different rearing environments
influenced behavior and gene expression, but did not alter monoamine levels or
metabolites. Specifically, compared to control fish, fish exposed to a simulated
predator environment tended to be less aggressive, more exploratory, and more
neophobic; and fish raised in both complex and variable social environments
tended to be less neophobic. Exposure to a simulated predator environment tended
to lower expression of dopamine receptor DRD4A, a complex environment increased
expression of dopamine receptor DRD1B, while a variable social environment tended
to increase serotonin receptor 5-HTR2B and serotonin transporter SLC6A4A
expression. Despite both behavior and gene expression varying with early
environment, there was no evidence that gene expression mediated the relationship
between early environment and behavior. Our results confirm that environmental
conditions early in life can affect phenotypic variation. However, the
mechanistic pathway of the monoaminergic systems translating early environmental
variation into observed behavioral responses was not detected.
PMID- 29961049
TI - The Microbiome and Acute Kidney Injury.
AB - Acute kidney injury (AKI) is a major clinical problem in native and transplanted
kidneys. Bidirectional interaction between gut microbiota and kidney tissue or
the "colo-renal" system is being recognized as an important modulating factor in
AKI. Gut microbes appear to have a complex but yet poorly understood
communication with renal cellular and molecular processes that affect normal
kidney function and response to injury. There have been major recent advances in
the study of the microbiome that provide an opportunity to apply this knowledge
to improve our understanding and treatment of patients with AKI. This mini-review
aims to focus on select general concepts about the microbiome, mechanisms by
which the microbiome can modify kidney function, and data on microbiome and AKI.
We have briefly touched on a few topics rather than comprehensively reviewing the
role of microbiome in kidney diseases. We also propose future gut microbiota-AKI
studies based on advances in gut microbiota studies in other human diseases and
experimental models.
PMID- 29961050
TI - SALTO - Study Protocol and Rationale of a Community-Oriented Obesity Prevention
Program in the Kindergarten.
AB - BACKGROUND: The prevalence of early childhood overweight and obesity in Austria
has reached average European levels of 20% in boys and 18% in girls. The
rationale and study protocol of SALTO, Salzburg Together against Obesity will be
presented, which is aimed to assist adults in increasing the rate of 4- to 6-year
old children with a healthy body weight. METHODS: A controlled longitudinal
sequential study design consisting of 14 intervention (IK) and 8 control (CK)
kindergarten was used to investigate the effect of actions tailored for teachers
and parents on BMI among 4- to 6-year-old children. The study launched in
November 2014 was approved by the ethics committee of the University of Salzburg.
RESULTS: 681 children, 181 parents (119 mothers, 62 fathers) and 30 teachers were
investigated until October 2016. Preliminary analyses revealed that more boys
(19%) and fathers (60% IK, 43% CK) were overweight and obese than girls (16%) and
mothers (19% IK, 20% CK). CONCLUSION: The challenges faced by the SALTO staff in
the implementation of health-promoting actions in the kindergarten are manifold.
The Community-Oriented Core Setting (COCS) intervention approach will show
whether the actions will reduce the percentage of obesity and be sustainable in
the long term.
PMID- 29961051
TI - Prevention Models of Childhood Obesity in Sweden.
AB - The impact of childhood obesity on the Swedish Health Care system is described.
Childhood Obesity and Diabetes Type 2 is increasing for the last 10 years, but
not Diabetes Type 1. Thus, prevention is needed. How to define prevention of
obesity? Could treatment of childhood obesity be regarded as prevention of adult
obesity? Of course it could, but we are lacking a long term follow-up from
childhood to adulthood. However, we know that childhood obesity is a risk factor
for adult disease. But we need long-lasting results in children to being able to
state that we have prevented adult obesity. What about treatment of children with
overweight, i.e. defined as the less severe level of an increased body weight as
opposed to obesity? There are few if any studies restricting the treatment only
to overweight children. Normally, obese children are treated, and some overweight
children are added usually to increase the study sample. Then of course promotion
of a healthy lifestyle could be of major interest. Finally, the traditional
concept of primary prevention seems to be the only solution that is realistic
according to many. However, there is no clear pattern when primary prevention
works.
PMID- 29961053
TI - A Randomized Clinical Trial of Flex 19G Needles versus 22G Needles for
Endobronchial Ultrasonography in Suspected Lung Cancer.
AB - BACKGROUND: A flexible 19-gauge (Flex 19G) needle has been developed for
endobronchial ultrasonography. OBJECTIVES: We aimed to evaluate quantitative and
qualitative specimen characteristics of Flex 19G in a randomized controlled
setting for patients with suspected lung cancer. METHODS: We undertook a single
center, randomized, controlled trial. A computer-generated randomization assigned
all enrolled patients 1: 1 to undergo endobronchial ultrasonography using a Flex
19G or a 22-gauge (22G) needle for lymph node tissue sampling. Pathologists were
blinded to the group assignment. The primary end point was histological tissue
core procurement. The secondary end points were diagnostic yield, specimen
bloodiness and overall quality, tissue surface area and performance for next
generation sequencing (NGS), and procedure-related complications. RESULTS:
Between June 2016 and February 2017, we randomly allocated a total of 78
patients: 39 patients to Flex 19G and 39 patients to 22G. No superiority in
tissue core procurement was observed for Flex 19G compared to 22G (67 vs. 72%, p
= 0.81). No significant difference was observed in diagnostic yield and overall
specimen quality, but transbronchial needle aspiration specimens by Flex 19G were
bloodier and had a larger tissue surface area. NGS was successful for clinically
relevant genes in 96% and for all 26 genes tested in 81% of the samples. There
was no difference in clinically relevant complications. CONCLUSIONS: No
superiority is observed for Flex 19G in histological tissue core procurement
rate. The Flex 19G needle could be considered when a larger tissue surface is of
special interest.
PMID- 29961052
TI - Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat
Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized
Controlled Trials.
AB - BACKGROUND/AIMS: Spinal cord injury (SCI) has long been a subject of great
interest in a wide range of scientific fields. Several attempts have been made to
demonstrate motor function improvement in rats with SCI after transplantation of
induced pluripotent stem cells (iPSC). This systematic review and meta-analysis
was designed to summarize the effects of iPSC on locomotor recovery in rat models
of SCI. METHODS: We searched the publications in the PubMed, Medline, Science
Citation Index, Cochrane Library, CNKI, and Wan-fang databases and the China
Biology Medicine disc. Results were analyzed by Review Manager 5.3.0. The quality
of evidence was assessed using the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) methodology. RESULTS: Six randomized
controlled preclinical trials covering eight comparisons and including 212 rats
were selected. The subgroup analyses were based on the following items: different
SCI models, cell counts, iPSC sources, iPSC differentiations and transplantation
methods. The pooled results indicated that iPSC transplantation significantly
improved locomotor recovery of rats after SCI by sustaining beneficial effects,
especially in the subgroups of contusion, moderate cell counts (5*105), source of
human fetal lung fibroblasts, iPSC-neural precursors and intraspinal injection.
CONCLUSION: Our meta-analysis of the effects of iPSC transplantation on locomotor
function in SCI models is, to our knowledge, the first meta-analysis in this
field. We conclude that iPSC transplantation improves locomotor recovery in rats
with SCI, implicating this strategy as an effective therapy. However, more
studies are required to validate our conclusions.
PMID- 29961054
TI - Puerarin Attenuates Osteoarthritis via Upregulating AMP-Activated Protein
Kinase/Proliferator-Activated Receptor-gamma Coactivator-1 Signaling Pathway in
Osteoarthritis Rats.
AB - BACKGROUND/AIMS: Osteoarthritis is the most common degenerative joint disease and
causes major pain and disability in adults. It has been reported that
mitochondrial dysfunction in chondrocytes was associated with osteoarthritis.
Puerarin has multiple effects including restoring mitochondrial function. In this
study, the potential effects of puerarin on osteoarthritis and osteoarthritis
associated mitochondrial dysfunctions were evaluated. METHODS: Osteoarthritis
rats were treated with puerarin and the severity of osteoarthritis and cartilage
damages was evaluated. The mitochondrial biogenesis and functions were analyzed
by measuring related proteins expression, mitochondrial DNA content, ATP
production, and oxygen consumption. The dependence of AMP-activated protein
kinase (AMPK) pathway on puerarin-regulated mitochondrial function was analyzed
by applying AMPK inhibitor Compound C. RESULTS: Puerarin treatment alleviated
mechanical hyperalgesia and cartilage damage in osteoarthritis rats. Puerarin
increased mitochondrial biogenesis and attenuated mitochondrial dysfunctions in
osteoarthritis rats. AMPK inhibitor Compound C abolished puerarin's effects.
CONCLUSION: Puerarin attenuates osteoarthritis by upregulating the
AMPK/proliferator-activated receptor-gamma coactivator signaling pathway in
osteoarthritis rats.
PMID- 29961055
TI - Prevention of Obesity in Childhood and Adolescence.
PMID- 29961056
TI - The Diagnostic Work-Up of Hypereosinophilia.
AB - Hypereosinophilia (HE) is defined as a persistent elevated eosinophil count of
>=1.5 * 109/L. HE can be one of the dominant manifestations of a hematopoietic
myeloid neoplasm or secondary/reactive to an underlying medical condition. If a
cause of HE and its associated tissue/organ damage is not determined, the
condition is considered to be idiopathic hypereosinophilic syndrome (HES). The
work-up of HE can be challenging due to a broad range of causes of HE that can be
either reactive or neoplastic. In recent years, with the advent of molecular
genetic testing and the introduction of targeted therapy in the management of
these patients, there is a growing interest in better characterization of these
diseases. Using a multimodality approach and following a proper -algorithm, a
diagnosis can be made in a large proportion of patients. In idiopathic HES,
myeloid neoplasm associated -somatic mutations as evidence of clonality are
reported in -20-25% patients; however, the mutation data should be -interpreted
cautiously considering the prevalence of clonal hematopoiesis of indeterminate
potential (CHIP). Bone marrow morphology has been shown to have important value
in the identification of a true myeloid neoplasm in these disorders. A genome
wide study may be needed to understand the "idiopathic" cases that would
ultimately lead to better patient care.
PMID- 29961058
TI - How Journals Treat Scientific Misconduct Allegations: Should Articles Be
Retracted?
PMID- 29961057
TI - A Partial Response at Week 4 Can Predict Subsequent Outcome during Lamotrigine
Augmentation Therapy in Treatment-Resistant Depressive Disorder: A Preliminary
Study.
AB - BACKGROUND/AIMS: The present study prospectively examined whether or not a
partial response at week 4 predicts subsequent response at week 8 during
lamotrigine augmentation therapy in 51 (16 males and 35 females) inpatients with
treatment-resistant depressive disorder using an open-study design. METHODS: The
subjects were 51 depressed patients who had already shown insufficient response
to at least 3 psychotropics including antidepressants, mood stabilizers, and
atypical antipsychotics. The diagnoses were major depressive disorder (n = 19),
bipolar I disorder (n = 9), and bipolar II disorder (n = 23). The final doses of
lamotrigine were 100 mg/day for 29 subjects who were not taking valproate and 75
mg/day for 22 subjects taking valproate. Depressive symptoms were evaluated by
the Montgomery-Asberg Depression Rating Scale (MADRS) before the start of
lamotrigine and then at week 4, and finally after the 8th week of treatment.
RESULTS: A significant linear relationship was found between percent improvements
in MADRS scores at weeks 4 and 8 (r = 0.492, y = 0.438x + 30.223, R2 = 0.226, p <
0.001). The receiver operating characteristics analysis indicated that a percent
improvement of 16% or greater at week 4 was significantly (p < 0.01) predictive
of response (50% or more reduction in the MADRS score). The patients were
significantly divided by the cut-off point into the responders and the
nonresponders (18/26 vs. 1/25, p < 0.001). CONCLUSION: The present study suggests
that a partial response at week 4 can predict subsequent outcome at week 8 during
lamotrigine augmentation therapy in patients with treatment-resistant depressive
disorder, and that the absence of a partial improvement at week 4 is highly
predictive of nonresponse.
PMID- 29961059
TI - Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing
the Renoprotective Effects of Potassium Supplementation in Chronic Kidney
Disease.
AB - BACKGROUND/AIMS: Dietary potassium (K+) has beneficial effects on blood pressure
and cardiovascular (CV) outcomes. Recently, several epidemiological studies have
revealed an association between urinary K+ excretion (as proxy for dietary
intake) and better renal outcomes in subjects with chronic kidney disease (CKD).
To address causality, we designed the "K+ in CKD" study. METHODS: The K+ in CKD
study is a multicenter, randomized, double blind, placebo-controlled clinical
trial aiming to include 399 patients with hypertension, CKD stage 3b or 4
(estimated glomerular filtration rate [eGFR] 15-44 mL/min/1.73 m2), and an
average eGFR decline > 2 mL/min/1.73 m2/year. As safety measure, all included
subjects will start with a 2-week open-label phase of 40 mmol potassium chloride
daily. Patients who do not subsequently develop hyperkalemia (defined as serum K+
>5.5 mmol/L) will be randomized to receive potassium chloride, potassium citrate
(both K+ 40 mmol/day), or placebo for 2 years. The primary end point is the
difference in eGFR after 2 years of treatment. Secondary end points include other
renal outcomes (> 30% decrease in eGFR, doubling of serum creatinine, end-stage
renal disease, albuminuria), ambulatory blood pressure, CV events, all-cause
mortality, and incidence of hyperkalemia. Several measurements will be performed
to analyze the effects of potassium supplementation, including body composition
monitoring, pulse wave velocity, plasma renin and aldosterone concentrations,
urinary ammonium, and intracellular K+ concentrations. CONCLUSION: The K+ in CKD
study will demonstrate if K+ sup-plementation has a renoprotective effect in
progressive CKD, and whether alkali therapy has additional beneficial effects.
PMID- 29961060
TI - Depression and Smoking Augment the Production of Circulating Autoantibodies
against Glycated HSA in Rheumatoid Arthritis Patients.
AB - BACKGROUND: Depression and smoking contribute to the prognosis of autoimmune
rheumatoid arthritis (RA). Advanced glycation end products (AGEs) are also
detected in RA patients. This study correlates RA in patients with various levels
of depression and a history of smoking through the detection of antibodies
against AGEs of proteins. METHODS: Sixty RA subjects were selected and divided
into 4 groups based on their levels of depression and smoking habits. The
division was as follows: group I consisted of RA patients classified as depressed
(RA-D); group II consisted of RA patients with a history of smoking (RA-S); group
III consisted of RA patients suffering from depression who were also smokers (RA
DS); and group IV consisted of patients with RA alone (RA-A), i.e., not depressed
and non-smokers. In vitro human serum albumin (HSA) was modified by glucose, and
the modifications were studied by biochemical and biophysical techniques.
Glycated (G)-HSA was used as an antigen, and autoantibodies against G-HSA (G-HSA
Abs) were screened in serum samples of different groups of RA subjects. Oxidative
stress levels in all patients and healthy individuals were analyzed by protein
bound carbonyl content estimations. RESULTS: Significant biochemical and
biophysical changes were detected in G-HSA when compared to native (N)-HSA. All
patients and control subjects were screened for circulating G-HSA-Abs and N-HSA
Abs. From the cohort of different samples, serum autoantibodies from RA-DS showed
a high recognition of G-HSA-Abs titres compared to RA-D or RA-S. RA-A exhibited
the least binding of circulating G-HSA-Abs of all the groups. The oxidative
stress marker, the carbonyl content also exhibited highest levels in RA-DS,
followed by RA-D and RA-S. Band shift assay showed the highest titres of
immunoglobulin G in the serum samples of RA-DS. CONCLUSIONS: Smoking and
concomitant depression in RA subjects may lead to enhanced oxidative stress
levels responsible for the gradual formation and/or exposing of cryptic epitopes
on HSA that induce the production of G-HSA-Abs. Hence, we postulate that by
reducing depression and corresponding oxidative stress, it may be possible to
control or limit the severity of the precipitation of RA disease activity and
improve prognosis.
PMID- 29961061
TI - Temporal and Vertical Variation in Microbial Community Composition in Response to
Physicochemical Characteristics in a Water Column of Highly Eutrophied Jinhae
Bay, South Korea.
AB - Microbial communities play an essential role in marine biogeochemical cycles.
Physical and biogeochemical changes in Jinhae Bay, the most anthropogenically
eutrophied bay on the coasts of South Korea, are well described, but less is
known about the associated changes in microbial communities. Temporal and
vertical variation in microbial communities at three depths (surface, middle, and
bottom) at seven time points (June to December) at the J1 sampling site were
investigated on the MiSeq platform based on the 16S rRNA gene. Overall, the
microbial community was dominated by Proteobacteria, Cyanobacteria, and
Bacteroidetes from June to November, whereas Firmicutes were dominant in
December, especially in the middle and bottom layers. The results indicate that
the microbial community composition strongly varied with temporal changes in the
physicochemical water properties. Moreover, the community composition differed
markedly between the surface and middle layers and the bottom layer in the
summer, when the water column was strongly stratified and bottom water hypoxia
developed. A redundancy analysis suggested a significant correlation between
physicochemical variables (i.e., temperature, salinity, and oxygen concentration)
and microbial community composition. This study indicates that temporal changes
in water conditions and eutrophication-induced hypoxia effectively shape the
structure of the microbial community.
PMID- 29961062
TI - Cell Death Pathways Drive Necroinflammation during Acute Kidney Injury.
AB - Renal tubules represent an intercellular unit and function as a syncytium. When
acute tubular necrosis was first visualized to occur through a process of
synchronized regulated necrosis (SRN) in handpicked primary renal tubules, it
became obvious that SRN actually promotes nephron loss. This realization adds to
our current understanding of acute kidney injury (AKI)-chronic kidney disease
(CKD) transition and argues for the prevention of AKI episodes to prevent CKD
progression. Because SRN is triggered by necroptosis and executed by ferroptosis,
2 recently identified signaling pathways of regulated necrosis, a combination
therapy employing necrostatins and ferrostatins may be beneficial for protection
against nephron loss. Clinical trials in AKI and during the process of kidney
transplantation are now required to prevent SRN. Additionally, necrotic cell
death drives autoimmunity and necroinflammation and therefore represents a
therapeutic target even for the prevention of antibody-mediated rejection of
allografts years after the transplantation process.
PMID- 29961063
TI - Maternal High-Fat Diet Promotes the Development and Progression of Prostate
Cancer in Transgenic Adenocarcinoma Mouse Prostate Offspring.
AB - BACKGROUND/AIMS: We aim to investigate the impact of maternal high fat diet (HFD)
on the development and progression of prostate cancer (PCa) in transgenic
adenocarcinoma mouse prostate (TRAMP) offspring. METHODS: The TRAMP model was
used, and divided into maternal HFD group and normal diet (ND) group in the
present study. Each group contained 36 TRAMP mice. Serum levels of leptin,
adiponectin, interleukin (IL) -1alpha, IL-1beta, IL-6, tumor necrosis factor
alpha and monocyte chemotactic protein-1 were measured by the 20th, 24th and 28th
week old through ProcartaPlex Multiplex Immunoassay. Body fat ratio was measured
by MiniQMR. Tumor formation rate was measured through hematoxylin and eosin (H&E)
staining, and mortality rate was measured meantime. Western blot was applied to
determine the levels of Protein Kinase B (Akt) and Phosphatase and tensin homolog
(PTEN). RESULTS: The mortality rate of maternal HFD group was significantly
higher than that of ND group (P = 0.046). The tumor formation rate was
significantly higher in maternal HFD group than in ND group only in 20th week
subgroup (P = 0.040). A significant increase of leptin was seen in maternal HFD
20th and 24th week subgroups (P = 0.001 and < 0.001, respectively) and a decrease
of adiponectin was seen in maternal HFD 20th and 28th week subgroups (P =0.006
and < 0.001, respectively). Besides, an activated phos-Akt (P-Akt) and
deactivated PTEN were observed in maternal HFD group. CONCLUSIONS: Maternal HFD
could increase the standard serum leptin level, inhibit the expression of PTEN
protein, promote P-Akt protein expression, activate the PI3K/Akt pathway, and
ultimately promote the development and progression of PCa in TRAMP offspring.
PMID- 29961064
TI - The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and
Growth-Related Hormone Concentrations: The SKOT Cohort Studies.
AB - BACKGROUND/AIMS: Exposure to obesity during pregnancy may lead to adverse changes
in the offspring's metabolic profile. We compared appetite- and growth-related
hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born
mainly to nonobese mothers (SKOT-I). METHODS: Infants from SKOT-I (n = 273) and
SKOT-II (n = 132) were examined including anthropometric measurements and blood
samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I),
adiponectin, and leptin. Information on breastfeeding and parental
characteristics were also collected. RESULTS: At 9 months of age, SKOT-II infants
were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers
were shorter. There was no difference in body mass index (BMI). SKOT-II infants
had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I
compared to SKOT-I infants (all p <= 0.015). These differences remained, except
for leptin, when adjusted for current weight. Breastfeeding versus
nonbreastfeeding at 9 months was associated with lower concentrations of all
hormones (all p <= 0.003). In adjusted models, maternal BMI at 9 months was
positively associated with insulin and adiponectin and negatively with IGF-I.
CONCLUSIONS: Pre-pregnancy obesity confers symmetrically larger infant body size
and higher levels of most growth- and appetite-related hormones but surprisingly
lower levels of IGF-I, suggesting other possible infant growth-promoting effects
through insulin.
PMID- 29961065
TI - Verbascoside Inhibits Glioblastoma Cell Proliferation, Migration and Invasion
While Promoting Apoptosis Through Upregulation of Protein Tyrosine Phosphatase
SHP-1 and Inhibition of STAT3 Phosphorylation.
AB - BACKGROUND/AIMS: As a natural antioxidant, verbascoside (VB) is proved to be a
promising method for the treatment of oxidative-stress-related neurodegenerative
diseases. Thus, this study aimed to investigate the effects of VB on glioblastoma
cell proliferation, apoptosis, migration, and invasion as well as the mechanism
involving signal transducer and activator of transcription 3 (STAT3) and Src
homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). METHODS: U87
cells were assigned to different treatments. The MTT assay was used to test cell
proliferation, flow cytometry was used to detect cell apoptosis, and a Transwell
assay was used for cell migration and invasion. We analyzed the glioblastoma
tumor growth in a xenograft mouse model. Western blot analysis was employed to
determine the protein expression of related genes. RESULTS: Glioblastoma cells
exhibited decreased cell proliferation, migration, invasion, and increased
apoptosis when treated with VB or TMZ. Western blot analysis revealed elevated
SHP-1 expression and reduced phosphorylated (p)-STAT3 expression in glioblastoma
cells treated with VB compared with controls. Correspondingly, in a xenograft
mouse model treated with VB, glioblastoma tumor volume and growth were decreased.
Glioblastoma xenograft tumors treated with VB showed elevated SHP-1, Bax, cleaved
caspase-3, and cleaved PARP expression and reduced p-STAT3, Bcl-2, survivin, MMP
2, and MMP-9 expression. siRNA-SHP-1 inhibited the VB effects on glioblastoma.
CONCLUSION: This study demonstrates that VB inhibits glioblastoma cell
proliferation, migration, and invasion while promoting apoptosis via SHP-1
activation and inhibition of STAT3 phosphorylation.
PMID- 29961066
TI - Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid
Leukemia of FAB Subtypes M0 and M1.
AB - BACKGROUND/AIMS: Acute myeloid leukemia (AML) of French-American-British (FAB)
subtypes M0 and M1 are both poorly differentiated AML, but their mutational
spectrum and molecular characteristics remain unknown. This study aimed to
explore the mutational spectrum and prognostic factors of AML-M0 and M1. METHODS:
Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were
enrolled in this study. Whole-genome sequencing was performed to depict the
mutational spectrum of each patient. Clinical characteristics at diagnosis,
including peripheral blood (PB) white blood cell counts (WBC), blast percentages
in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent
genetic mutations were described. Survival was estimated using the Kaplan-Meier
methods and log-rank test. Univariate and multivariate Cox proportional hazard
models were constructed for event-free survival (EFS) and overall survival (OS),
using a limited backward elimination procedure. RESULTS: Forty-six patients had
more than five recurrent genetic mutations. FLT3 had the highest mutation
frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1
(n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate
analysis showed that age >=60 years and TP53 mutations had adverse effect on EFS
(P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC
count >=50*109/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034,
respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and
allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all
P< 0.001). Multivariate analysis suggested that allo-HSCT and NPM1 mutations were
independent favorable prognostic factors for EFS and OS (all P< 0.05), WBC count
>=50*109/L was an independent risk factor for EFS (P=0.002) and TP53 mutations
for OS (P=0.043). CONCLUSIONS: Our study provided new insights into the
mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that
FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML
M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT.
PMID- 29961067
TI - Persistence and Transcription of Paternal mtDNA Dependent on the Delivery
Strategy Rather than Mitochondria Source in Fish Embryos.
AB - BACKGROUND/AIMS: Mitochondria (MT) and mitochondrial DNA (mtDNA) show maternal
inheritance in most eukaryotic organisms; the sperm mtDNA is usually delivered to
the egg during fertilization and then rapidly eliminated to avoid heteroplasmy,
which can affect embryogenesis. In our previous study, fertilization-delivered
sperm mtDNA exhibited late elimination and transcriptional quiescence in cyprinid
fish embryos. However, the mechanisms underlying elimination and transcriptional
quiescence of paternal mtDNA are unclear. METHODS: Goldfish and zebrafish were
used to investigate the fate of mtDNAs with different parental origins delivered
by fertilization or microinjection in embryos. Goldfish MT from heart, liver and
spermatozoa were microinjected into zebrafish zygotes, respectively. Specific PCR
primers were designed so that the amplicons have different sizes to characterize
goldfish and zebrafish cytb genes or their cDNAs. RESULTS: The MT injection
delivered paternal mtDNA from sperm, as well as those from the heart and liver,
was capable of persistence and transcription until birth, in contrast to the
disappearance and transcriptional quiescence at the heartbeat stage of
fertilization-delivered sperm mtDNA. In addition, the exogenous MT-injected
zebrafish embryos have normal morphology during embryonic development.
CONCLUSIONS: The fate of paternal mtDNA in fishes is dependent on the delivery
strategy rather than the MT source, suggesting that the presence of sperm
factor(s) is responsible for elimination and transcriptional quiescence of
fertilization-delivered sperm mtDNA. These findings provide insights into the
mechanisms underlying paternal mtDNA fate and heteroplasmy in cyprinid fishes.
PMID- 29961068
TI - MRI Changes in the Thalamus and Basal Ganglia of Full-Term Neonates with
Perinatal Asphyxia.
AB - BACKGROUND: Magnetic resonance imaging (MRI) is the standard neuroimaging
technique to assess perinatal asphyxia-associated brain injury in full-term
infants. Diffusion-weighted imaging (DWI) is most informative when assessed
during the first week after the insult. OBJECTIVES: To study the DWI
abnormalities of the thalamus and basal ganglia in full-term infants with
perinatal asphyxia. METHODS: Fifty-five (near) term infants (normothermia n = 23;
hypothermia n = 32) with thalamus and/or basal ganglia injury were included. MRI
findings were assessed visually and quantitatively calculating apparent diffusion
coefficient (ADC) values. Thalamus/basal ganglia ADC ratios were calculated to
analyze the differences between these areas. Infants with an early MRI (days 1-3)
or later MRI (days 4-7) were compared. RESULTS: Isolated extensive thalamic
injury was seen early, and focal thalamic and basal ganglia injury was seen
later. On the early MRI, visual assessment underestimated abnormalities in the
basal ganglia (59% abnormal vs. 90% abnormal on quantitative assessment; p =
0.015), suggesting the need for quantitative assessment. In infants treated with
hypothermia, the thalamus/basal ganglia ADC ratio was lower. CONCLUSIONS: Both
visual analysis and quantitative evaluation of cerebral MRI after perinatal
asphyxia are needed, especially during the first few days after birth. Timing of
ADC changes is influenced by therapeutic hypothermia.
PMID- 29961069
TI - Differential Impact of Chronic Kidney Disease on Coronary Calcification and
Atherosclerosis in Asymptomatic Individuals with or without Diabetes: Analysis
from a Coronary Computed Tomographic Angiography Registry.
AB - AIM: The aim of this study was to assess the combined effects of chronic kidney
disease (CKD) and diabetes on the extent and developmental pattern of coronary
artery disease (CAD). METHODS: A total of 3,017 self-referred asymptomatic
individuals without known CAD who underwent 64-channel dual-source coronary
computed tomography angiography between 2006 and 2010 were enrolled. The patients
were divided into six groups based on their diabetes status (nondiabetic or
diabetic) and estimated glomerular filtration rate (eGFR) (eGFR > 90 mL/min/1.73
m2, normal renal function; eGFR 60-89, mild CKD; or eGFR 30-59, moderate CKD). We
compared the coronary artery calcium score (CACS), segment stenosis score (SSS),
and >=50% obstructive CAD among the groups. RESULTS: In nondiabetics, whereas SSS
and >=50% obstructive CAD were not different as renal function deteriorated,
after adjusting for cardiovascular risk factors, CACS showed a unique
developmental pattern: no CACS increase until mild CKD, but abrupt increase from
the stage of moderate CKD (moderate vs. normal renal function, adjusted OR 5.118,
95% CI 1.293-20.262, p = 0.020). In diabetics, patients from the stage of mild
CKD were more likely to have >=50% obstructive CAD (p = 0.004), higher CACS (p =
0.020), and SSS (p = 0.001) in multivariable analysis. CONCLUSIONS: The presence
of CKD did not have a significant impact on the development of coronary
atherosclerosis, but affected the progression of coronary calcification more
markedly from the stage of moderate CKD in nondiabetics. However, in diabetics,
the deterioration of renal function was significantly associated with the
development of coronary atherosclerosis and calcification from the stage of mild
CKD.
PMID- 29961071
TI - Prognostic Models Associated with 6-Month Survival of Patients Admitted to
Nursing Homes.
AB - BACKGROUND: Health status and the needs presented by people admitted to nursing
homes make it necessary to contemplate aspects such as prognosis to offer quality
palliative care. OBJECTIVE: To compare the prognostic utility in nursing homes of
two prognostic models of 6-month survival based on the Palliative Prognostic
Index (PPI) or Palliative Performance Status (PPS) instruments and palliative
needs indicators. METHODS: A longitudinal prospective observational and
analytical cohort study of survival and prognostic models in 88 patients with
palliative needs (assessed by the NECPAL-ICO-CCOMS(c)) from an Andalusian (Spain)
nursing home was performed. Sociodemographic and clinical variables were
assessed, and 6 months later, in September 2017, survival was checked. Multiple
logistic regression analysis was performed using the R-Commander program (version
3.2.2). RESULTS: Two models of the logistic regression analysis met the fit
criteria. The two models combined the Surprise Question, the presence of
persistent symptoms, and the clinical indicators of severity from the NECPAL
tool, in addition to the Charlson Comorbidity Index, and varied only in terms of
the latter variable, including the PPI in the first model and the PPS in the
second. In the first model, significant associations were identified between 6
month survival and the persistent symptoms variable (OR = 7.78, p = 0.025, 95% CI
= 1.45-60.92) and PPI (OR = 1.94, p < 0.001, 95% CI = 1.21). In the second model,
6-month survival was also significantly associated with the persistent symptoms
variable (OR = 4.57, p = 0.045, 95% CI = 1.07-22.41) and the PPS (OR = 0.93, p =
0.001, 95% CI = 0.88-0.96). CONCLUSIONS: Prognostic models such as ours that
include variables commonly included in clinical assessments can help nursing home
professionals prioritize and ensure adequate mobilization of palliative care
resources, which are very limited in these institutions.
PMID- 29961070
TI - PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling
Pathway.
AB - BACKGROUND/AIMS: Tyrosine kinase inhibitor gefitinib significantly improves the
survival of patients with non-small-cell lung cancer (NSCLC) by inhibiting
epidermal growth factor receptor (EGFR) tyrosine kinase. However, patients
eventually develop resistance to gefitinib through uncharacterized mechanisms. It
is known that plasminogen activator urokinase receptor (PLAUR) plays an important
role in cell proliferation, migration and apoptosis. However, the role of PLAUR,
particularly exosomal PLAUR in gefitinib resistance in NSCLC has not been
reported. The aim of this study is to determine the relationship between PLAUR
and gefitinib resistance. METHODS: In this study, a tethered cationic lipoplex
nanoparticle (TCLN) biochip containing molecular beacons was used as probes to
detect PLAUR mRNA in plasma exosomes from patients with gefitinib-sensitive and
resistant NSCLC. In vitro, Real-time PCR was used to examine the expression of
PLAUR mRNA and Western blot was applied to examine the expression of related
proteins. The gene knockdown was achieved by Lentivirus based RNA silence
technique. The cell counting kit-8 assay and EdU incorporation were used to
examine cell proliferation. The flow cytometry was applied to determine cell
apoptosis and cell cycle, while the mitochondrial membrane potential was measured
by JC-1 dye assay. Signaling pathway affected by PLAUR knockdown was identified
by cDNA Microarray. The effect of PLAUR knockdown on tumorigenesis was analyzed
in vivo. RESULTS: We found that the exosomal PLAUR mRNA in the plasma of
gefitinib-resistant NSCLC patients was significantly increased compared to that
of gefitinib-sensitive NSCLC patients. The PLAUR mRNA and soluble PLAUR protein
were also significantly increased in gefitinib-resistant human lung
adenocarcinoma PC9R cells compared to gefitinib-sensitive PC9 cells. Silencing
PLAUR in PC9R cells impaired mitochondrial membrane potential and increased cell
apoptosis via EGFR/p-AKT/survivin signaling pathway. Furthermore, EGFR was
upregulated in the geftinib-resistant PC9R cells, and knockdown of EGFR
significantly increased cell apoptosis. CONCLUSIONS: Taken together, our results
demonstrated that PLAUR induces geftinib-resistance through EGFR/p-AKT/survivin
signaling pathway in gefitinib-resistant human lung adenocarcinoma cells. PLAUR
could be a novel therapeutic target for gefitinib-resistant NSCLC patients.
PMID- 29961072
TI - Aortic Angulation Does Not Impact Outcomes in Self-Expandable or Balloon
Expandable Transcatheter Aortic Valve Replacement.
AB - OBJECTIVES: The role of aortic angulation in attenuating procedural success in
balloon-expandable (BE) and self-expandable (SE) transcatheter aortic valve
replacement (TAVR) has been controversial. METHODS: We retrospectively assessed
patients undergoing SE and BE TAVR who had an aortic angle measured on
multidetector computed tomography at a single tertiary referral center. The
primary outcome was device success, measured per the Valve Academic Research
Consortium-2 criteria. Clinical outcomes at 30 days (including mortality) were
also assessed. RESULTS: A total of 251 patients were identified; 182 patients
received a BE valve and 69 patients an SE valve. The median aortic angle was 46.8
degrees (range 24.4-70 degrees ) in the BE group and 43.3 degrees (range 20-71
degrees ) in the SE group. In multivariate logistic regression analysis, aortic
angulation did not affect device success. Mortality at 30 days and 12 months and
postprocedural clinical outcomes were similarly not associated with aortic
angulation. CONCLUSION: In this cohort of patients undergoing BE and SE TAVR over
a wide range of aortic angles, we found no associations between angle and device
success or any other clinical metrics. Increased aortic angulation does not
adversely affect outcomes in BE or SE TAVR.
PMID- 29961073
TI - A Natural Occurring Mouse Model with Adgrv1 Mutation of Usher Syndrome 2C and
Characterization of its Recombinant Inbred Strains.
AB - BACKGROUND/AIMS: Our laboratory discovered a Kunming mouse with enormous
electroretinogram (ERG) defects. Its auditory brainstem response (ABR) threshold
was significantly elevated and closely resembled the features of Usher syndrome
(USH). This study sought to cross these USH-like mice (named KMush/ush mice) with
CBA/CaJ mice to establish recombinant inbred strains and identify their
phenotypes and genotypes. METHODS: KMush/ush mice were crossed with CBA/CaJ mice
to establish inbred strains by sibling mating. ERG, ABR, ocular fundus
morphology, histological examinations of the retina and inner ear, quantitative
real-time polymerase chain reaction, western blotting, and exon sequencing were
performed to assess the phenotypes and genotypes of the offspring strains.
RESULTS: The F1 hybrids from crossing KMush/ush and CBA/CaJ mice had normal ERG
and ABR responses. The F2 offspring from intercrossing the F1 mice showed a
segregation of the retinitis pigmentosa (RP) and hearing loss phenotypes. The CBA
1ush/ush mice had an RP phenotype that was characterized by a vanished ERG
waveform and loss of the outer nuclear layer. Their Pde6b gene had a nonsense
mutation that resulted in the failure of protein production in western blotting.
However, the ABR threshold of this strain of mice was normal. The CBA-2ush/ush
mice had normal retinal function and architecture. Their ABR threshold was
increased, with a dramatic degeneration of the stereocilia bundles in the outer
hair cells of the inner ear. Whole exome sequencing and exon sequencing revealed
a deletion of one base pair in exon 31 of the Adgrv1 gene, which would result in
the premature termination of protein encoding. The level of Adgrv1 mRNA was
reduced in the CBA-2ush/ush mice. The CBA-3ush/ush mice had phenotypes of RP,
elevated ABR threshold, and degeneration of the stereocilia bundles in the outer
hair cells. They were closely associated with the nonsense mutations of Pde6b and
Adgrv1, respectively. CONCLUSION: We isolated a mouse strain with hearing loss
from inbred mice with retinal degeneration and established it as a recombinant
inbred strain with a spontaneous mutation in Adgrv1, the human Usher syndrome 2C
gene. The retinal degeneration was cause by a mutation in Pde6b, while the
hearing loss was caused by a mutation in Adgrv1.
PMID- 29961074
TI - Testicular Function and Bone in Young Men with Severe Childhood-Onset Obesity.
AB - BACKGROUND: Previous studies suggest increased risk for hypoandrogenism and
fractures in men with obesity. We aimed to describe the effects of severe
childhood-onset obesity on the cross talk between metabolic state, testes, and
skeleton at late puberty. METHODS: A cohort of adolescent and young adult males
with severe childhood-onset obesity (n = 21, mean age 18.5 years) and an age
matched control group were assessed for testicular hormones and X-ray
absorptiometry-derived bone mass. RESULTS: Current median body mass indexes for
the obese and control subjects were 37.4 and 22.9. Severe early-onset obesity
manifested with lower free testosterone (median [interquartile range] 244 [194
332] vs. 403 [293-463] pmol/L, p = 0.002). Lower insulin-like 3 (1.02 [0.82-1.23]
vs. 1.22 [1.01-1.46] ng/mL, p = 0.045) and lower ratio of testosterone to
luteinizing hormone (2.81 [1.96-3.98] vs. 4.10 [3.03-5.83] nmol/IU, p = 0.008)
suggested disrupted Leydig cell function. The degree of current obesity inversely
correlated with free testosterone (tau = -0.516, p = 0.003), which in turn
correlated positively with bone area at all measurement sites in males with
childhood-onset obesity. CONCLUSIONS: Severe childhood-onset obesity is
associated with impaired Leydig cell function in young men and lower free
testosterone may contribute to impaired skeletal characteristics.
PMID- 29961075
TI - Effect of Bisphenol A Glycol Methacrylate on Virulent Properties of Streptococcus
mutans UA159.
AB - Bisphenol A glycidyl methacrylate (bis-GMA), which is released into the oral
environment by dental composites through incomplete polymerization, hydrolysis,
and mechanical degradation, can significantly influence oral ecology around resin
based materials. The purpose of this study was to investigate how bis-GMA changes
the virulence properties of Streptococcus mutans, a major cariogenic bacterium in
humans. The results show that bis-GMA not only inhibited the planktonic growth of
cells in medium containing glucose, fructose, or mannose, but also reduced the
viability of S. mutans. However, the presence of bis-GMA increased sugar
transport and intracellular polysaccharide accumulation in S. mutans, thereby
increasing the potential of cell persistence. In addition, bis-GMA could enhance
S. mutans's adhesion to hard surfaces and glucan synthesis, which could
contribute to biofilm formation. Although free bis-GMA made cells vulnerable to
acidic stress, it also provided increased resistance to hydrogen peroxide, which
might confer an advantage in competition with other oral microorganisms during
the early stage of biofilm development. Interestingly, the presence of bis-GMA
did not change the ability of S. mutans to interact with saliva. The results
suggest that leachable bis-GMA could contribute to biofilm-related secondary
dental caries at the marginal interface between resin-based materials and teeth
by altering the virulent properties of S. mutans, although bis-GMA reduced the
planktonic growth and viability of S. mutans.
PMID- 29961076
TI - Selection and Investigation of a Primate Model of Spontaneous Degenerative Knee
Osteoarthritis, the Cynomolgus Monkey (Macaca Fascicularis).
AB - BACKGROUND The aim of this study was to identify a primate model of degenerative
knee osteoarthritis (KOA) that may be more relevant for research studies on
degenerative KOA in humans. MATERIAL AND METHODS Sixteen specific-pathogen-free
(SPF) male cynomolgus monkeys (Macaca fascicularis) were divided into group A
(n=8), an old group (22.0-25.3 years of age), and group B (n=8), a young group
(3.0-5.2 years of age). For each primate, the behavior was observed, knee
circumference was measured, knee joint X-rays were performed, and peripheral
blood white blood cell (WBC) counts were measured, and the Kellgren and Lawrence
(K-L) system was used for the classification of osteoarthritis. An enzyme-linked
immunoassay (ELISA) was performed on knee joint fluid to measure levels of
interleukin (IL)-1beta, transforming growth factor (TGF)-beta1, and matrix
metalloproteinase (MMP)13. Changes in articular cartilage were evaluated using
the Brittberg score and the Mankin histopathology grading score, respectively.
Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and
Western blot were used to measure the expression of the NOTCH3, JAG1, and ACAN
genes in knee cartilage specimens, and the findings in the two groups of primates
were compared. RESULTS Seven old aged primates in group A were compared with
group B, and showed significant differences in WBC count, synovial fluid IL
1beta, TGF-beta1, and MMP13 levels, expression levels of the NOTCH3, JAG1, and
ACAN genes in knee cartilage specimens, and in the Brittberg and Mankin scores
(all, P<0.05). CONCLUSIONS Cynomolgus monkeys (Macaca fascicularis) might be a
model for age-related degenerative KOA.
PMID- 29961077
TI - The Value of Pre-Infarction Angina and Plasma D-Dimer in Predicting No-Reflow
After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Acute
Myocardial Infarction Patients.
AB - BACKGROUND Primary percutaneous coronary intervention (PCI) has improved outcomes
greatly in patients with ST-elevation myocardial acute infarction (STEMI).
However, the no-reflow phenomenon significantly reduces its efficacy. MATERIAL
AND METHODS In this study, we investigated the value of combining plasma D-dimer
level on admission and pre-infarction angina (PIA) in predicting no-reflow
phenomenon in STEMI patients after primary PCI. A total of 926 STEMI patients who
underwent primary PCI were included. RESULTS The average age was 52.6 years, 617
(66.6%) of them had experienced a PIA, and 435 (47.9%) showed no-reflow
phenomenon after primary PCI. Both PIA and plasma D-dimer on admission were
independent predictors of no-reflow, with a risk of 0.516 (95% CI: 0.380 to
0.701) and 2.563 (95% CI: 1.910 to 3.439), respectively. Plasma D-dimer level had
an area under curve (AUC) of 0.604 (95% CI: 0.568~0.641) in predicting no-reflow
phenomenon, and PIA had an AUC of 0.574 (95% CI: 0.537 to 0.611). Importantly,
the new signature combining D-dimer level on admission and PIA showed an
increased AUC (0.637, 95%CI: 0.601 to 0.673) in predicting the no-reflow
phenomenon. Moreover, the patients with high D-dimer level on admission but
without PIA had significantly increased ratio of no-reflow phenomenon and in
hospital mortality compared to the other patients (P<0.001 and P=0.041,
respectively). CONCLUSIONS Based on these solid results, we conclude that
combining plasma D-dimer level on admission and PIA might create a good signature
for use in predicting the no-reflow phenomenon after primary PCI in STEMI
patients.
PMID- 29961078
TI - Foot Morphology in Chinese School Children Varies by Sex and Age.
AB - BACKGROUND Knowledge of children's foot shape is essential for podiatric
healthcare and footwear design. Differences in foot shapes relative to sex and
age were demonstrated among white children; however, no study has examined the
foot characteristics of Asian children according to sex and age. This study aimed
to analyze the age- and sex-associated differences in foot measurements in
Chinese children. MATERIAL AND METHODS We recruited 1240 boys and 1303 girls from
China as participants for the present study. Foot dimensions were recorded by a
video filming system, and 12 foot-shape measurements were acquired. One-way ANOVA
was used to calculated the changes in measurements with age for boys and girls.
Scores were analyzed as raw and normalized to foot length using the independent
samples t test. RESULTS Most measurements increased significantly at 7-8 and 8-9
years for girls and 8-9 and 10-11 years for boys. Arch height, instep length, and
heel width showed greatest increases for both sexes ages 7-12 years (P<0.05). Sex
differences in measurements mainly occurred at 8, 9, and 11 years. When we
analyzed the normalized measurements of the same age children, instep length,
heel width, ball girth, and instep girth were significantly different between
boys and girls (P<0.05). CONCLUSIONS Sex- and age-associated differences were
identified in the foot morphology of the Chinese school-aged children in this
study. These differences should be considered when making clinical decisions
about normal foot development and manufacturing shoes for Chinese school
children.
PMID- 29961080
TI - CAR-T in the clinic: drive with care.
PMID- 29961079
TI - Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet
ring cell cancer.
AB - Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in
gastric cancer, however, with no systematical investigation for prognostic
genomic features. Here we report a systematic investigation conducted in 1868
Chinese gastric cancer patients indicating that signet-ring cells content was
related to multiple clinical characteristics and treatment outcomes. We thus
perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent
CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation,
prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet
ring cell content, age at diagnosis, female/male ratio, and TNM stage.
Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes,
and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which
is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26
introduced cell lines. Overall, this study provides insights into the clinical
and genomic features of SRCC, and highlights the importance of frequent CLDN18
ARHGAP26/6 fusions in chemotherapy response for SRCC.
PMID- 29961081
TI - Scientific basis of the OCRA method for risk assessment of biomechanical overload
of upper limb, as preferred method in ISO standards on biomechanical risk
factors.
AB - We are writing in regards to Armstrong et al's recent discussion paper (1), which
addresses the scientific basis of ISO standards on biomechanical risk factors and
more specifically the OCRA methodology. The paper comments on the ISO's working
methods, but it will be up to the ISO to respond if it sees fit to do so. As the
authors of the OCRA method, we wish to respond in a individual capacity. For
several years, we have belonged to an ISO working group (ISO TC 159/SC3/WG4)
advocating methods for the assessment of biomechanical overload risk; the members
of the working group come from various countries and represent public
authorities, social partners and researchers with particular expertise in this
field. Our decision to send this letter to the editor was motivated by the
following position put forth in Armstrong et al's paper concerning the rigor of
development of the ISO ergonomics standards: "The production of the ISO
ergonomics standards differed substantially from the writing of evidence-based
practical guidelines. According to the limited information provided in the
published documents, the ISO ergonomics standards were not based on a systematic
search and appraisal of available literature. It is not clear why the ISO
subcommittee preferred one method of risk assessment over others. For instance,
the ISO 11228-3 identified three detailed risk assessment methods for repetitive
hand exertions at high frequency: OCRA (a concise index for the assessment of
exposure to repetitive movements of the upper limbs) (20), ACGIH hand activity
level (HAL) (21), and the Strain Index (22), but preferred the OCRA methods
without providing a scientific basis or comparison (eg, intra- and inter-observer
reliability, strength of association with musculoskeletal disorders (MSD), etc.)
even though such comparisons are available in the literature (13, 23). As a
result, some statements in ISO 11228-3 appear to be based on personal opinions
and are in contrast with scientific evidence from the literature. For instance,
the ISO standard includes a statement "in many epidemiological surveys it (OCRA)
has shown itself to be well related with health effects (such as the occurrence
of UL-WMSD [upper limb-work related MSD)]" (13). This statement was not supported
by a well-designed epidemiological study in 2007 when the ISO standard was
published (19). Indeed, in 2010, Takala and colleagues noted the absence of
longitudinal studies on the association between the OCRA index and the risk of
MSD. They also pointed out the absence of studies on the repeatability of the
OCRA method (13)". (Note: the references in italic relate to the original paper).
We would like to point out that the ISO standards in question (2) were actually
developed by the working group, as mandated by ISO, over the period 2000-2004.The
years leading up to the publication of the standard (2005-2007) were dedicated to
the challenging task of democratically seeking the endorsement of the ISO member
countries. During this time, no significant changes could be made to the basic
text other than those arising from specific observations or comments from the
countries. This needs to be taken into account, especially when debating the
references underpinning the standard. More specifically, the standard in question
(ISO 11228-3) (2) in Annex A, clearly states that the general reference model for
assessing "repetitive, high frequency, low load movements of the upper limbs" is
a Consensus Document, drafted and published in 2001 by the IEA-Technical
Committee on Musculoskeletal Disorders, with the endorsement of the International
Commission on Occupational Health (ICOH) (3). The study considered at least 14
different methods that have over time been suggested in the literature as briefly
summarized in the same ISO standard (2). The recommendations set forth in this
vital Consensus Document went on to become the basis for choosing the most
appropriate methods to suggest to future users through the standard (OCRA; ACGIH
Hand Activity Level (HAL); Strain Index), each with their respective merits and
limits in compliance with the criteria set out in the Consensus Document and
taking into account their applicability in the field and ability to interpret the
results of the risk assessment. It is against this background, and in light of
the rationale described in Annex A, that the entire group agreed that the OCRA
method was to be considered as the "preferred" method, insofar as it was deemed
to best match the recommendations laid out in the aforementioned Consensus
Document. Furthermore the OCRA method was, at the time, the only risk assessment
method supported by the results of several epidemiological, albeit cross
sectional studies, uniquely available in literature. The study was based on a
very large number of cases (>5000 cases) with results both of risk evaluation of
upper-limb biomechanical overload (using the OCRA method) and of musculo-skeletal
clinical examination (assessing the corresponding diseases). Such studies were
reported in a special issue of Ergonomics (4), in an updated paper - first
published in Italian (5) - also in Ergonomics (6), in the books edited by
Elsevier (7), and CRC Taylor & Francis (8). This risk/damage database enabled an
estimation (within defined limits) of the risk of upper-limb work-related
musculoskeletal disorders at a given OCRA index level. Starting from the
established relation among risk indexes and percent of pathological subjects, it
was possible to determine the risk limit values provided by the ISO standard (2).
With reference to the alleged absence of studies on the repeatability of the OCRA
method, we prefer to mention the most recent results obtained by other
researchers, rather than our findings, acknowledging the good "inter-rater
reliability" of the OCRA Checklist, and stating that "the OCRA Checklist inter
rater reliability scores were among the highest reported in the literature for
semi-quantitative physical exposure assessment tools of the upper extremity" (9)
As for the scientific base, we suggest Armstrong et al (1) could get more
valuable information about the OCRA methodology looking not only to the 1996
special issue in Italian language (10) - the only publication they mention
dealing specifically with OCRA - but to the many updated publications. Some of
the most relevant publications in English (as suggested by the publisher) are
mentioned in the references here below. Many other publications and manuals in
English, Italian, Spanish and Portuguese are available but not reported here due
to limitation of space. A complete list of our publications can be found on our
website: www.epmresearch.org, where some of the articles are available for
download. Simple tools (Excel spreadsheets) for carrying out risk assessments by
OCRA can also be freely downloaded from the same website. The validity and
usability of OCRA methodology can also be indirectly confirmed by its extensive
use around the world. For example, a recent search on ScienceDirect
(www.sciencedirect.com/science/journals/all/full-text-access) has recently shown
that more than 477 works dealing with OCRA hae been published by different
authors in indexed journals to date. In conclusion, we recommend the authors of
the discussion paper (1) deepen their analysis of the OCRA methodology [beyond
the only cited old 1996 paper (10)] before expressing definite conclusions about
the scientific value of the OCRA methodology and about the entire ISO standard
setting system. Our team is always happy to engage with the scientific community
and end users of studies on biomechanical overload, as we have also done within
the ISO for many years now. ISO working groups arguably offer valuable
opportunities to come together at the international level and table discussions
between researchers and users. We are researchers who have devoted our life's
work to prevention, and intend to continue striving towards that goal, with
everyone's help and without bickering, bias, vested interests, or professional
rivalry. The health and well-being of workers is all we have ever cared about. We
have always been ready to cooperate with those who share this vital objective.
References 1. Armstrong T J, Burdorf I A, Descatha A, Farioli A, Graf M, Horie S,
Marras W S, Potvin J R, Rempel D, Spatari G, Takala E P, Verbeek J, Violante FS.
Scientific basis of ISO standards on biomechanical risk factors. Scand J Work
Environ Health - online first. https://doi.org/10.5271/sjweh.3718 2. ISO. ISO
11228-3. Ergonomics - Manual handling - Handling of low loads at high frequency.
ISO, 2007. Geneva, Switzerland. 3. Colombini D, Occhipinti E, Delleman D,
Fallentin N, Kilbom A, Grieco A. Exposure assessment of upper limb repetitive
movements: a consensus document in W. Karwowski International Encyclopaedia of
Ergonomics and Human Factors, New York: Taylor & Francis, 2001. 4. Colombini D,
Grieco A, Occhipinti E. Occupational musculoskeletal disorders of the upper limbs
due to mechanical overload. Ergonomics. Special issue;1998:41(9). 5. Occhipinti,
E., Colombini, D. Metodo OCRA: aggiornamento dei valori di riferimento e dei
modelli di previsione dell'occorrenza di UL-WMSDs nelle popolazioni lavorative
esposte a movimenti e sforzi ripetuti degli arti superiori. [The OCRA method:
update of UL-WMSDs reference values and prediction models of occurrence in
working populations exposed to repetitive movements and strains of the upper
limbs]. La Medicina del Lavoro, 2004. 95;4:305-319 6. Occhipinti E, Colombini D.
Updating reference values and predictive models of the OCRA method in the risk
assessment of work-related musculoskeletal disorders of the upper limbs.
Ergonomics; 2007,50(11):1727-1739. https://doi.org/10.1080/00140130701674331 7.
Colombini D, Occhipinti E, Grieco A. Risk assessment and management of repetitive
movements and exertions of upper limbs. Amsterdam: Elsevier Science, 2002. 8.
Colombini D, Occhipinti E. Risk analysis and management of repetitive actions: a
guide for applying the OCRA system (occupational repetitive actions). New York:
CRC press, 2016. 9. Paulsen R, Gallu T, Gilkey D, Reiser R, Murgia L, Rosecrance
J. The inter-rater reliability of Strain Index and OCRA Checklist task
assessments in cheese processing. Applied Ergonomics. 2015;51,199-204.
https://doi.org/10.1016/j.apergo.2015.04.019 10. Occhipinti E, Colombini D.
Proposal of a concise index for the evaluation of the exposure to repetitive
movements of the upper extremity (OCRA index)]. Med Lav. Special issue, 1996 Nov
Dec; 87(6): 526-548.
PMID- 29961082
TI - Authors' response: Letter to the Editor concerning OCRA as preferred method in
ISO standards on biomechanical risk factors.
AB - We thank Drs. Colombini and Occhipinti for their personal reply to our Discussion
Paper (1, 2). We share the overall goal of preventing workplace injuries and
welcome a discussion of the ISO process on workplace ergonomics standards; this
was the primary aim of the Discussion Paper. We hope that other members of the
relevant ISO working groups will also participate in the discussion. However,
Drs. Colombini and Occipinti misinterpret our paper. Our aim was not to
"addresses the scientific basis of ISO standards on biomechanical risk factors
and more specifically the OCRA methodology". The purpose was to point out that
"while the ISO process has value, it has also clear limitations when it comes to
developing occupational health and safety standards that should be based on
scientific principles". It is true that our paper discussed the OCRA method, but
only as an example, in a single paragraph. We noted that the OCRA method was
promoted as the preferred method by the ISO working group even though there were
other risk assessment methods which, at the time (and currently), were at least
as scientifically valid (3). The discovery that, while on the ISO working group,
Drs. Colombini and Occipinti elevated the risk assessment method that they
developed (OCRA) over the other methods, demonstrates one of several limitations
of the ISO process, namely, the lack of attention to conflict of interest.
Finally, we would like to draw attention to the note by Drs. Colombini and
Occhipinti that "the ISO standards in question were actually developed by the
working group, as mandated by ISO, over the period 2000-2004". This long-elapsed
time, without an update to the standard, should be a concern for all scientists
given the large quantity of quality scientific literature published since then
(eg, 3-6). Fourteen years is well beyond what is recommended in the ISO
guidelines. References 1. Colombini D, Occhipinti E. Scientific basis of the OCRA
method for risk assessment of biomechanical overload of the upper limb, as
preferred method in ISO standards on biomechanical risk factors. Scand J Work
Environ Health - online first. https://doi.org.10.5271/sjweh.3746 2. Armstrong T
J, Burdorf I A, Descatha A, Farioli A, Graf M, Horie S, Marras W S, Potvin J R,
Rempel D, Spatari G, Takala E P, Verbeek J, Violante FS. Scientific basis of ISO
standards on biomechanical risk factors. Scand J Work Environ Health - online
first. https://doi.org/10.5271/sjweh.3718 3. Takala EP, Pehkonen I, Forsman M,
Hansson GA, Mathiassen SE, Neumann WP, Sjogaard G, Veiersted KB, Westgaard RH,
Winkel J. Systematic evaluation of observational methods assessing biomechanical
exposures at work. Scand J Work Environ Health. 2010;36:3-24.
https://doi.org/10.5271/sjweh.2876 4. Paulsen R, Gallu T, Gilkey D, Reiser R,
Murgia L, Rosecrance J. The inter-rater reliability of Strain Index and OCRA
Checklist task assessments in cheese processing. Applied Ergonomics. 2015; 51,199
204. https://doi.org/10.1016/j.apergo.2015.04.019 5. Kapellusch JM, Gerr FE,
Malloy EJ, Garg A, Harris-Adamson C, Bao SS, Burt SE, Dale AM, Eisen EA, Evanoff
BA, Hegmann KT, Silverstein BA, Theise MS, Rempel DM. Exposure-response
relationships for the ACGIH threshold limit value for hand-activity level:
results from a pooled data study of carpal tunnel syndrome. Scand J Work Environ
Health. 2014;40:610-20. https://doi.org/10.5271/sjweh.3456 6. Violante FS,
Farioli A, Graziosi F, Marinelli F, Curti S, Armstrong TJ, Mattioli S,
Bonfiglioli R. Carpal tunnel syndrome and manual work: the OCTOPUS cohort,
results of a ten-year longitudinal study. Scand J Work Environ Health.
2016;42:280-90. https://doi.org/10.5271/sjweh.3566.
PMID- 29961083
TI - Focal traumatic rupture of a dermoid cyst in a pediatric patient: case report and
literature review.
AB - BACKGROUND: Dermoid cysts are rare congenital teratomas that can occasionally
rupture and cause chemical meningitis, neurological deficit, or hydrocephalus.
Rarely, dermoid cysts in the pediatric population can rupture spontaneously and
even more rarely rupture due to trauma. To date, there are only five documented
cases of traumatic rupture of a dermoid cyst. A 2-year-old male presented with 5
days of left eye ptosis and ophthalmoplegia after suffering a fall and was found
to have a ruptured left anterior clinoid dermoid cyst that was surgically
resected. The patient had significant improvement postoperatively. SIGNIFICANCE:
To the authors' knowledge, this is the first reported case in the literature of a
ruptured dermoid cyst after trauma in a pediatric patient and the first case of a
traumatically ruptured dermoid cyst presenting with neurological deficit.
PMID- 29961084
TI - Hydatid disease (Echinococcus) of the central nervous system.
AB - Hydatid disease of the central nervous system is rare and comprises about 2-3% of
all the hydatid cyst cases reported in the world. Spinal hydatid is still rare.
It is endemic in sheep and cattle-raising regions, seen mainly in Mediterranean
countries including Turkey and Syria. Pediatric neurosurgeons in nonendemic
countries face a challenge when they are encountered with hydatid cyst of the
central nervous system due to lack of awareness and diagnostic dilemmas. It is
also a mammoth economic problem in developing countries due to improper hygiene
and lack of dedicated veterinary practice. The clinical features are largely
nonspecific. However, with the advent of MR imaging, the diagnostic accuracy has
increased. Intact removal of the cyst without causing any spillage is the goal
and key to cure. In this manuscript, the current literature on hydatid cyst of
the brain and spine is reviewed to understand the epidemiological, diagnostic
accuracy and advances in therapeutics. A heightened clinical suspicion about
hydatid disease, role of MR imaging and improving surgical strategies is
discussed. A nationwide prevention of the disease is the ultimate goal.
PMID- 29961085
TI - Endoscopic versus open approach in craniosynostosis repair: a systematic review
and meta-analysis of perioperative outcomes.
AB - INTRODUCTION: Surgery for craniosynostosis remains a crucial element in
successful management. Intervention by both endoscopic and open approaches has
been proven effective. Given the differences in timing and indications for these
procedures, differences in perioperative outcomes have yet to be thoroughly
compared between the two approaches. The aim of the systematic review and meta
analysis was to assess the available evidence of perioperative outcomes between
the two approaches in order to better influence the management paradigm of
craniosynostosis. METHODS: We followed recommended PRISMA guidelines for
systematic reviews. Seven electronic databases were searched to identify all
potentially relevant studies published from inception to February 2018 which were
then screened against a set of selection criteria. Data were extracted and
analyzed using meta-analysis of proportions. RESULTS: Twelve studies satisfied
all the selection criteria to be included, which described a pooled cohort
involving 2064 craniosynostosis patients, with 965 (47%) and 1099 (53%) patients
undergoing surgery by endoscopic and open approaches respectively. When compared
to the open approach, it was found that the endoscopic approach conferred
statistically significant reductions in blood loss (MD = 162.4 mL), operative
time (MD = 112.38 min), length of stay (MD = 2.56 days), and rates of
perioperative complications (OR = 0.58), reoperation (OR = 0.37) and transfusion
(OR = 0.09), where all p < 0.001. CONCLUSION: Both endoscopic and open approaches
for the surgical management of craniosynostosis are viable considerations. The
endoscopic approach confers a significant reduction in operative and
postoperative morbidity when compared to the open approach. Given that specific
indications for either approach should be considered when managing a patient, the
difference in perioperative outcomes remain an important element of this
paradigm. Future studies will validate the findings of this study and consider
long-term outcomes, which will all contribute to rigor of craniosynostosis
management.
PMID- 29961086
TI - Extended release versus immediate release tacrolimus in kidney transplant
recipients: a systematic review and meta-analysis.
AB - PURPOSE: To compare the estimated glomerular filtration rate (eGFR) at 12 months
together with other outcomes among adult kidney transplant recipients (KTRs) who
received extended release, once daily tacrolimus (ER-Tac) compared to those who
received the immediate release, twice daily tacrolimus (IR-Tac) administration.
METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) Statement, we systematically reviewed all randomized
controlled trials (RCTs) that compared clinical outcomes between ER-Tac versus IR
Tac in KTRs. The systematic searches were conducted on PubMed, EMBASE, Cochrane
Register of Controlled Trials, Scopus, Web of Science, and CINAHL without
language restriction. The trials registered and reference lists were also
searched and reviewed. Data were extracted for eGFR, serum creatinine (Scr),
creatinine clearance (CrCl), biopsy-proven acute rejection rate (BPAR), graft
survival, and overall patient survival at different times over 24 months after
kidney transplant (KT). A meta-analysis was performed to integrate the results
from eligible studies. RESULTS: From 1145 articles screened, 11 RCTs were
included. The pooled results of included RCTs showed no significant difference of
eGFR at 12 months between ER-Tac and IR-Tac groups (four trials, n = 1738; mean
difference - 0.77 mL/min/1.73 m2, 95% CI: - 2.41 to 0.87; p = 0.56; I2 = 0%).
Comparing between the two tacrolimus formulations, there were no significant
differences of eGFR, CrCl, Scr, BPAR, graft survival, and patient survival at
different times over 4 years after transplantation. CONCLUSIONS: Based upon
currently available evidences in KTRs, the impact on kidney allograft function
appears to be comparable between ER-Tac and IR-Tac.
PMID- 29961087
TI - Properties of short-latency responses in the upper limbs evoked by axial impulses
during leaning: evidence for reticulospinal projections.
AB - We studied the short-latency (SL) effects of postural perturbations produced by
impulses applied over the spine of the C7 vertebra or the sternum ("axial
impulses") in 12 healthy subjects. EMG recordings were made bilaterally from the
triceps brachii, biceps brachii, soleus, and tibialis anterior muscles, and
unilaterally from the deltoid, forearm flexors, forearm extensors, and first
dorsal interosseous (FDI) muscles. Sternal impulses evoked short-latency
responses in the biceps when subjects leaned posteriorly to support approximately
12% of their body weight with the arms, but these responses were only modestly
larger than for isometric contraction of the arms (26.3 vs. 14.7%). In contrast,
clear excitatory responses could be evoked in the deltoid, triceps, forearm
muscles, and FDI when leaning anteriorly to support similar amounts of body
weight. These responses were significantly larger than during isometric
contraction. The deltoid (42.5%) and triceps (44.7%) had the largest responses in
supported anterior lean and onset latencies increased distally in this condition
(mean 31.8 ms in deltoid to 53.7 ms in FDI). There was a disproportionate delay
between the forearm muscles and FDI. For both directions of lean, postural reflex
responses normally present in the legs were severely attenuated. SL upper limb
excitatory responses were bigger in proximal muscles as well as larger and more
widespread for anterior axial perturbations compared to posterior axial
perturbations when using the arms to support body weight. Our findings also
provide further evidence of a role for reticulospinal pathways in mediating these
rapid postural responses to accelerations of the trunk.
PMID- 29961088
TI - Should you stop wearing neckties?-wearing a tight necktie reduces cerebral blood
flow.
AB - PURPOSE: Negative cerebrovascular effects can be expected by compressing jugular
veins and carotids by a necktie. It was already demonstrated that a necktie
increases intraocular pressure. In many professions, a special dress code
including a necktie and a collared shirt is mandatory although little is known
about the effect of this "socially desirable strangulation." METHODS: In this
study, the effect of wearing a necktie concerning cerebral blood flow and jugular
venous flow by magnetic resonance imaging. Thirty volunteers were divided in two
groups. One underwent MRI with necktie, the other without. RESULTS: The
examination resulted in a statistically significant decrease of CBF after
tightening the necktie (p < 0.001) while the venous flow did not show any
significant changes. CONCLUSION: It appears that wearing a necktie leads to a
reduction in CBF.
PMID- 29961089
TI - Reaction to Koppen et al., 'Assessing colonic anatomy normal values based on air
contrast enemas in children younger than 6 years'.
PMID- 29961090
TI - Concerning our publication 'Assessing colonic anatomy normal values based on air
contrast enemas in children younger than 6 years': reply to M. D. Levin.
PMID- 29961091
TI - Baseline knee joint effusion and medial femoral bone marrow edema, in addition to
MRI-based T2 relaxation time and texture measurements of knee cartilage, can help
predict incident total knee arthroplasty 4-7 years later: data from the
Osteoarthritis Initiative.
AB - OBJECTIVE: To evaluate if baseline pathological knee conditions as assessed via
single features of the MR-based Whole-Organ Magnetic Resonance Imaging Scoring
(WORMS), standard T2, and T2 gray-level co-occurrence matrix (GLCM) texture
parameters of knee cartilage can serve as potential long-term radiological
predictors of incident total knee arthroplasty (TKA) 4-7 years later. MATERIALS
AND METHODS: Baseline 3-T knee MRIs of 309 subjects from the Osteoarthritis
Initiative (n = 81 TKA cases, with right-knee TKA 4-7 years after enrolment, and
n = 228 TKA-free matched controls) were evaluated for the presence and severity
of pathological knee conditions via modified WORMS. Knee cartilage was segmented
and standard T2 cartilage and T2 GLCM texture measures (contrast, variance) were
computed. Statistical analysis employed conditional logistic regression. RESULTS:
We found that a one-point increase on the joint effusion scale, the bone marrow
edema scale or on the cartilage lesion scale at baseline predicted incident TKA
(ORs: 2.45, 1.65, and 1.37 respectively (p <= 0.003)). For T2 cartilage
measurements, we observed that in the lateral femur, a 1-SD increase in T2
relaxation time yielded a 28% increase in the odds of TKA (1.28 [1.09-1.643], p =
0.046). When looking at cartilage texture, we similarly noted that a 1-SD
increase in the cartilage texture parameter "contrast" was associated with a 33
40% increased risk of incident TKA in the lateral femur and tibia (0.003 <= p <=
0.021), as was a 1-SD increase in the texture parameter "variance" in the lateral
femur (p = 0.002). CONCLUSION: Radiological evaluation of standard knee MR images
via single WORMS features and T2 standard and texture analysis at baseline can
help predict the patient's individual risk for an incident TKA 4-7 years later.
PMID- 29961092
TI - On determining the power of digital PCR experiments.
AB - The experimental design that will be carried out to evaluate a nucleic acid
quantification hypothesis determines the cost and feasibility of digital
polymerase chain reaction (digital PCR) studies. Experiment design involves the
calculation of the number of technical measurement replicates and the
determination of the characteristics of those replicates, and this in accordance
with the capabilities of the available digital PCR platform. Available digital
PCR power analyses suffer from one or more of the following limitations: narrow
scope, unrealistic assumptions, no sufficient detail for replication, lack of
source code and user-friendly software. Here, we discuss the nature of six
parameters that affect the statistical power, i.e., desired effect size, total
number of partitions, fraction of positive partitions, number of replicate
measurements, between-replicate variance, and significance level. We also show to
what extent these parameters affect power, and argue that careful design of
experiments is needed to achieve the desired power. A web tool, dPowerCalcR, that
allows interactive calculation of statistical power and optimization of the
experimental design is available.
PMID- 29961093
TI - Outcome of kinematic alignment using patient-specific instrumentation versus
mechanical alignment in TKA: a meta-analysis and subgroup analysis of randomised
trials.
AB - INTRODUCTION: Kinematic alignment (KA) in total knee arthroplasty (TKA) matches
component position to the pre-arthritic anatomy of an individual patient, with
the aim of improving functional outcomes. Recent randomised controlled trials
(RCTs) comparing KA to traditional neutral mechanical alignment (MA) have been
mixed. This collaborative study combined raw data from RCTs, aiming to compare
functional outcomes between KA using patient-specific instrumentation (PSI) and
MA, and whether any patient subgroups may benefit more from KA technique.
MATERIALS AND METHODS: A literature search in PubMed, EMBASE and Cochrane
databases identified four randomised controlled trials comparing patients
undergoing TKA using PSI-KA and MA. Unpublished data including Western Ontario
McMaster Universities Arthritis Index (WOMAC) and Knee Society Score (KSS) were
obtained from study authors. Meta-analysis compared MA to KA change (post-op
minus pre-op) scores. Subgroup-analysis on KA patients looked for subgroups more
likely to benefit from KA and the impact of PSI accuracy. RESULTS: Meta-analyses
of change scores in 229 KA patients versus 229 MA patients were no different from
WOMAC (mean difference 3.4; 95% confidence interval - 0.5 to 7.3), KSS function
(1.3, - 3.9 to 6.4) or KSS combined (7.2, - 0.8 to 15.2). A small advantage was
seen for KSS pain in the KA group (3.6, 95% CI 0.2-7.1). Subgroup-analysis showed
no difference between varus, valgus and neutral pre-operative alignment groups,
and those who did and did not achieve KA plans. Pain-free patients at 1-year were
more likely to achieve KA plans. CONCLUSION: Patient-reported outcome scores
following TKA using PSI-KA are similar to MA. No identifiable subgroups benefited
more from KA, and long-term results remain unknown. Inaccuracy of the PSI system
used in KA patients could potentially affect outcome.
PMID- 29961094
TI - Profile of fibrosis-related gene transcripts and megakaryocytic changes in the
bone marrow of myelodysplastic syndromes with fibrosis.
AB - Bone marrow fibrosis (MF) in myelodysplastic syndromes (MDS) is associated with
an adverse prognosis. It is likely that molecular changes similar to those in
primary myelofibrosis (PMF) lead to MDS-MF, but gene expression profiling has not
yet been carried out. We analysed bone marrow biopsy samples by PCR, qPCR (45
transcripts per sample), and immunohistochemistry from MDS patients with fibrosis
(n = 70/119; including 19/70 MF0 > MF follow-up cases), MDS without fibrosis (n =
49/119), and 33 controls. SRSF2 and JAK2 mutations were detectable in up to 13%
including 3/19 follow-up cases with evidence of clonal evolution during MF
progression. MDS-MF showed increased expression of thrombospondin 1 (THBS1), TIMP
metallopeptidase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGFB1),
matrix metallopeptidases 2 and 14 (MMP2, MMP14), SMAD family members 3 and 4
(SMAD3, SMAD4), and miR-146b. Paralleling MF progression, a subfraction of follow
up cases showed megakaryocytic changes with increased CD42b+ pro-platelet
deposition in the bone marrow. In summary, fibrosis in MDS-MF and PMF shows many
molecular and morphological similarities.
PMID- 29961095
TI - Bioabsorbable screws, whatever the composition, can result in symptomatic intra
osseous tibial tunnel cysts after ACL reconstruction.
AB - PURPOSE: To describe the clinical results of patients who underwent surgical
treatment for a intra-osseous tibial tunnel cyst on a bioabsorbable interference
screw following anterior cruciate ligament reconstruction (ACL). METHODS: This
retrospective study included all patients who underwent surgery between 2004 and
2016 for an intra-osseous tibial tunnel cyst on bioabsorbable interference screw
following ACL reconstruction. The diagnosis was suggested clinically by pretibial
pain at the incision site, sometimes associated with a palpable subcutaneous
nodule and then confirmed on MRI. The first stage of surgery included exploratory
arthroscopy followed by open excision/curettage of the cyst and then the tunnel
was filled. The main criterion for outcome was a clinically normal knee (no pain,
0-120 range of motion, stable, with no effusion) at 6 months of follow-up.
RESULTS: This series included 53 patients, mean age 35.3 +/- 9.9 years old w ith
a mean 4.6 +/- 3.1 years (between 3.1 months and 19 years) of follow-up after
ligament reconstruction. The tibial screw was completely absorbed in 9/53 (17%)
of patients, and fragmented in 22/53 (41.5%). At the 6-month follow-up, 42/53
(79.2%) patients had a normal knee, 11/53 (20.8%) persistent pain in the cyst
area, 52/53 (98.1%) normal range of motion and 53 (100%) a stable knee. A
recurrent cyst developed at 2 years of follow-up in one patient. CONCLUSION:
Complete absorption of a bioabsorbable interference screw is long, increasing the
risk of developing intra-osseous tibial cysts during this period. The development
of new materials with improved absorption properties is needed. LEVEL OF
EVIDENCE: IV-Retrospective study.
PMID- 29961096
TI - A new, MRI-based classification system for tibial spine fractures changes
clinical treatment recommendations when compared to Myers and Mckeever.
AB - PURPOSE: Tibial spine fractures (TSFs) are graded according to the Meyers and
McKever (MM) classification system, which is based on a qualitative evaluation of
plain radiographs. However, although MRI images can provide important information
about these fractures, there is no MRI-based classification system. This study
aims to (1) establish the intra- and inter-rater reliability of the MM system for
use with radiographs, (2) propose a quantitative, MRI-based system and compare
its reliability to the MM system, and (3) assess how often using the MRI-based
system changes the classification and potential treatment plan as previously
determined using MM. METHODS: The MRI-based system was designed with three grades
based on quantitative displacement patterns of the fractured fragment and tissue
entrapment. Four raters from a tertiary care center evaluated 20 fractures
according to the MM and MRI-based systems. Observers graded images at two time
points at least 2 weeks apart, after which we compared the intra- and inter-rater
reliability of each system (using Fleiss' kappa and weighted kappa, respectively)
and assessed how often using the MRI-based system changed the fracture grade.
RESULTS: Both the MM and MRI-based systems exhibit fair to moderate intra- and
inter-rater reliability (average kappa values ranged from 0.38 to 0.66). Use of
the MRI-based system changed the fracture grade and as a result modified the
treatment recommendations in 32.5% of cases: 6.9% were previously unnoticed
fractures, 13.1% underwent a raise in grade, and 12.5% were graded as lower than
before. CONCLUSION: The MRI-based system is as reliable as the MM system and
provides specific, quantitative criteria for classifying fractures according to
fragment displacement and tissue entrapment. The new MRI-based system potentially
clarifies treatment indications for TSFs. LEVEL OF EVIDENCE: Diagnostic Study,
Level II.
PMID- 29961097
TI - Due to great variability fixed HKS angle for alignment of the distal cut leads to
a significant error in coronal TKA orientation.
AB - PURPOSE: For coronal alignment in total knee arthroplasty (TKA) most surgeons use
the patient's individual hip-knee shaft (HKS) angle (angle between the anatomical
axis and the mechanical axis of the femur). The major problem of the sole use of
HKS angle is that the individual patient's distal femoral asymmetry is not
considered. The purpose of this study was to determine the variability of the HKS
angle, the mechanical femoral angle (FMA) and to evaluate whether or not one of
the two angles is more important for TKA alignment strategy. It was the
hypothesis that HKS and FMA are not directly related to each other and hence HKS
should not be considered as guide for coronal alignment. METHODS: Prospectively
collected CT data of 1480 consecutive patients who underwent 3D reconstructed CT
scans before TKA was used for this retrospective registry study [882 women and
598 men, mean age +/- standard deviation 71 +/- 9 years (34-99 years)]. The CT
protocol was modified according to the Imperial Knee Protocol, which is a lowdose
CT protocol that includes high-resolution 0.75-mm slices of the knee and 3-mm
slices of the hip and ankle joints. All measurements were done using Symbios(r)
3D knee preoperative planning's software (Symbios, Yverdon les Bains,
Switzerland). The HKS, FMA and hip-knee-ankle (HKA) angles were measured. Angles
measured were displayed as mean, standard deviation (SD) and range. In addition,
the angles were shown as percentages after categorization. The HKS was
categorized between 3 degrees and 9 degrees in 1 degrees increments. The FMA
was categorized between 83.5 degrees and 98.5 degrees in 3 degrees increments.
The HKA was categorized between 12.5 degrees varus 5.5 degrees valgus in 3
degrees increments. Pearson correlations were used to investigate correlation of
HKS and FMA (p < 0.05). RESULTS: The HKS angle was not constant at 7 degrees but
averaged 6 degrees , and ranged from 2.5 degrees to 9 degrees . The FMA angle
was on average 93 degrees but varied more than 20 degrees , ranging from 75
degrees (varus) to 104 degrees (valgus). The mean HKA +/- SD was - 3.4 degrees
+/- 5.7 degrees (range - 23.0 degrees to 15.0 degrees ). The mean HKSSD was 5.6
degrees +/- 0.9 degrees (range 2.5 degrees -8.8 degrees ). The mean FMASD was
92.6 degrees +/- 2.8 degrees (range 75.2 degrees -103.5 degrees ). The Pearson
correlations of all measured angles are presented in Table 1. HKS significantly
correlated negatively with HKA and FMA (p < 0.001). FMA and HKA were strongly
correlated with each other (p < 0.0001). Considering the HKS angle as a constant
angle can induce a deviation of up to 5 degrees with respect to an orthogonal
distal femoral cutting objective. The great variability of the FMA angle implies
that the FMA seems more relevant than the HKS angle to define the strategy of
realignment of the lower limb. However, then patient specific instrumentation has
to be used to precisely transfer the planning to the surgical technique. Having
the aim of a more personalized TKA alignment in mind the individual
constitutional knee phenotype should be taken into account.
PMID- 29961098
TI - A novel signal transduction system for development of uric acid biosensors.
AB - Uric acid (UA) is an important biomarker for clinical diagnosis. Here, we present
a novel signal transduction system for the development of UA biosensors with the
characteristics of stability and ease-of-use. In this system, bacterial
allosteric transcription factor HucR was used as the bio-recognition element, and
the competition between HucR and the restriction endonuclease HindIII-HF to bind
to the designed DNA template was employed to enable signal transduction of UA
recognized by HucR. The presence of UA can induce conformational change of HucR,
which dissociates HucR from the designed DNA template, allowing the access of the
competitor HindIII-HF to cut this DNA template. Thus, the signal of UA recognized
by HucR is transduced to easily detectable DNA signal. As proof-of-concept, we
demonstrated two UA biosensors by coupling this signal transduction system with
real-time quantitative PCR (RT-qPCR) and amplified luminescent proximity
homogeneous assay (Alpha), respectively. The RT-qPCR-based UA biosensor has a
detection limit of 5 nM with a linear range up to 300 nM UA; Alpha-based UA
biosensor has a detection limit of 30 nM with a linear range of 100 nM-10 MUM.
Moreover, the robustness of both biosensors was verified by reliably detecting UA
present in a human serum sample. Altogether, the novel UA biosensors developed in
this work hold great potential for clinical application.
PMID- 29961099
TI - Efficacy of heat-labile enterotoxin B subunit-adjuvanted parenteral porcine
epidemic diarrhea virus trimeric spike subunit vaccine in piglets.
AB - Devastating outbreaks of porcine epidemic diarrhea (PED) started in China in late
2010 and rapidly spread to North America and Asia causing severe diarrhea and
high mortality in neonatal piglets, indicating that a new generation of vaccine
against porcine epidemic diarrhea virus (PEDV) is urgently needed. In the present
study, to mimic the native spike (S) glycoprotein, a stable cell line producing
the trimeric ectodomain of S glycoprotein of the PEDV Pintung-52 (PEDV-PT) strain
was successfully established by incorporating T4 bacteriophage foldon sequence of
fibritin trimerization domains at the C-terminal end and replacing the signal
peptide of S protein with the tissue plasminogen activator signal peptide
sequence at the N terminal end. The trimeric structure, bio-reactivity to PEDV
specific antibodies, and the N-glycosylation level of the recombinant S protein
were characterized. To induce systemic and mucosal immunity, conventional 5-week
old piglets were immunized with the trimeric S glycoprotein combined with the B
subunit of Escherichia coli heat-labile enterotoxin (LTB) by the intramuscular
(IM) route. As compared with the control group, all piglets in the S protein-LTB
immunized (IM PEDV S-LTB) group generated systemic PEDV S-specific IgG and
neutralizing antibody in blood but a low level of fecal PEDV-specific IgA and
limited protection against challenge of PEDV-PT strain. Our results suggest that
the recombinant PEDV trimeric S glycoprotein could be a potential subunit vaccine
candidate against PEDV, but IM immunization with LTB as the adjuvant provided
insufficient protection. The development of a vaccine regimen for inducing
mucosal immunity is an important task for generating a successful subunit vaccine
against PEDVs.
PMID- 29961100
TI - Concepts and applications of foliar spray for microbial inoculants.
AB - Damages of the (agro)ecosystem by extensive use of chemical fertilizers and
pesticides, the global dying of bee populations possibly linked to pesticide
spraying, and stricter regulations for pesticide use together with successful use
of microbials in IPM programs are pushing on the development and
commercialization of new microbial products and a large and growing biostimulants
and biocontrol market. This review focuses on microbial inoculants including
bacteria, fungi, and viruses used as biostimulant or biocontrol agent for foliar
application and covers all important steps from inoculant development to
successful field application. Topics presented comprise typical spraying
equipment including the importance of the spraying process and relating effects,
furthermore formulation development including classification and adjuvants, and
thirdly regulatory aspects as currently applied or under discussion. Microbial
inoculants for foliar spray reported in scientific literature are summarized and
contrasted with selected commercial products. Special attention is given to
factors most important in microbial spray: (a) type of active ingredient
(bacteria, fungi, viruses), (b) mode of action (ingestion, contact, competition),
(c) interaction with the plant leaf surface, (d) droplet size in terms of microbe
concentration and leaf coverage, and (e) environmental conditions during
spraying. Finally, we want to emphasize that timely administration is of utmost
importance for successful spraying and maximum efficacy. This might be supported
by weather stations and disease/pest models as an important step towards
precision farming.
PMID- 29961101
TI - Standardization of red flags for referral to rheumatologists and ophthalmologists
in patients with rheumatic diseases and ocular involvement: a consensus
statement.
AB - Ocular involvement is a common manifestation of inflammatory rheumatic diseases,
often requiring a multidisciplinary collaboration between rheumatologists and
ophthalmologists. The aim of this study was to standardize "red flags" for
referral for rheumatologists and ophthalmologists using a Delphi consensus for
the management of rheumatic diseases with ocular involvement. The scientific
board comprised 11 Italian hospital-based rheumatologists (N = 6) and
ophthalmologists (N = 5). A systematic review identified potential red flags for
referral. The panel developed 19 statements consisting of (a) referral from
ophthalmologist to rheumatologist (b) referral from rheumatologist to
ophthalmologist and (c) overarching principles relating to multidisciplinary
roles/goals and management. Voting was performed anonymously using an online
Delphi method. Each participant expressed a level of agreement on each statement
using a 5-point scale (1="strongly disagree"; 5="strongly agree"). Total
cumulative agreement was defined as the sum of the percentage of response to
items 4 ("agree") and 5 ("absolutely agree"), consensus defined as >= 80%
cumulative agreement for each statement. Positive consensus among 11 participants
was reached for 15/19 (78.9%) statements. Statements not reaching consensus were
discussed in a face-to-face meeting prior to the second vote (10 participants).
Positive consensus was reached for all 19 statements, with final total cumulative
agreement of 90-100%. This is the first Delphi consensus undertaken to
standardize red flags for referral to rheumatologists and ophthalmologists for
patients with rheumatic diseases and ocular involvement.
PMID- 29961102
TI - Multi-environment QTL analysis of plant and flower morphological traits in
tetraploid rose.
AB - KEY MESSAGE: Rose morphological traits such as prickles or petal number are
influenced by a few key QTL which were detected across different growing
environments-necessary for genomics-assisted selection in non-target
environments. Rose, one of the world's most-loved and commercially important
ornamental plants, is predominantly tetraploid, possessing four rather than two
copies of each chromosome. This condition complicates genetic analysis, and so
the majority of previous genetic studies in rose have been performed at the
diploid level. However, there may be advantages to performing genetic analyses at
the tetraploid level, not least because this is the ploidy level of most breeding
germplasm. Here, we apply recently developed methods for quantitative trait loci
(QTL) detection in a segregating tetraploid rose population (F1 = 151) to unravel
the genetic control of a number of key morphological traits. These traits were
measured both in the Netherlands and Kenya. Since ornamental plant breeding and
selection are increasingly being performed at locations other than the production
sites, environment-neutral QTL are required to maximise the effectiveness of
breeding programmes. We detected a number of robust, multi-environment QTL for
such traits as stem and petiole prickles, petal number and stem length that were
localised on the recently developed high-density SNP linkage map for rose. Our
work explores the complex genetic architecture of these important morphological
traits at the tetraploid level, while helping to advance the methods for marker
trait exploration in polyploid species.
PMID- 29961104
TI - Uncommon barotrauma while on high-flow nasal cannula.
PMID- 29961103
TI - The early flowering trait of an emmer wheat accession (Triticum turgidum L. ssp.
dicoccum) is associated with the cis-element of the Vrn-A3 locus.
AB - KEY MESSAGE: We identified a novel allele of the Vrn-A3 gene that is associated
with an early flowering trait in wheat. This trait is caused by a cis-element
GATA box in Vrn-A3. To identify novel flowering genes in wheat, we investigated
days from germination to heading (DGH) in tetraploid wheat accessions. We found
that the tetraploid variety Triticum turgidum L. ssp. dicoccum (TN26) harbors
unknown genes that surpass the earliness effect of the early flowering allele Ppd
A1a harbored by TN28 (T. turgidum L. ssp. turgidum conv. pyramidale). Using
recombinant inbred lines resulting from a cross between TN26 and TN28, we
performed a quantitative trait locus (QTL) analysis for DGH. We identified a QTL
for earliness in TN26 on chromosome 7AS, the chromosome on which Vrn-A3 is
located. By sequence analysis for the Vrn-A3 locus in both TN26 and TN28, we
identified a 7-bp insertion that included a cis-element GATA box sequence at the
promoter region of the Vrn-A3 locus of TN26. Based on an expression analysis
using sister lines for Vrn-A3, we suggest that the early flowering trait of TN26
was caused by the GATA box in Vrn-A3. In addition, we identified tetraploid wheat
as a useful genetic resource for wheat breeding.
PMID- 29961105
TI - Building communities of respect in the intensive care unit.
PMID- 29961107
TI - Routine multi detector computed tomography evaluation of tracheal impairment
compared to laryngo-tracheal endoscopy in children with vascular ring.
AB - PURPOSE: The aim of this study is to compare free-breathing routine multi
detector computed tomography (MDCT) and laryngo-tracheal (LT) flexible endoscopy
in the evaluation of tracheal impairment in children with vascular ring (VR).
MATERIALS AND METHODS: We performed a retrospective and monocentric study of all
patients with VR from 1997 to 2014. Clinical data included: initial symptoms,
type of surgery and clinical outcome. MDCT were blindly reviewed by two
radiologists in consensus, independently of LT endoscopy results. Radiologic and
endoscopic results were reviewed according to four criteria: percentage of
tracheal narrowing, distance of the compression from carina, presence of
bronchial compression and signs of tracheomalacia (TM). Concordance was evaluated
for each criterion with a Spearman coefficient. RESULTS: From 1997 to 2016, 21
patients with a vascular ring were operated on, among which 57% by thoracoscopy:
double aortic arch (n = 14), Neuhauser anomaly (n = 4) and Right aorta + aberrant
right subclavian artery (n = 3). 90% of them presented with respiratory symptoms
among which 43% of stridor. Chest X-ray was suggestive of VR in 87% of the cases.
MDCT images and LT endoscopy results were available and analyzed for nine
patients. Concordance (Spearman correlation coefficient) was excellent for
percentage and level of tracheal narrowing (1) and good for TM (0.79).
CONCLUSION: Free breathing routine MDCT is a reliable exam compared to LT
endoscopy in the evaluation of tracheal impairment in children with VR. In case
of respiratory symptoms (except stridor) and suggestive chest X-ray of VR,
endoscopy could be avoided and routine MDCT alone performed.
PMID- 29961106
TI - Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in
older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC)
cohort study.
AB - AIMS/HYPOTHESIS: We aimed to evaluate the link between severe hypoglycaemia and
domain-specific cognitive decline, smaller brain volumes and dementia in adults
with type 2 diabetes, which so far has been relatively poorly characterised.
METHODS: We included participants with diagnosed diabetes from the community
based Atherosclerosis Risk in Communities (ARIC) study. At the participants'
fifth study visit (2011-2013), we examined the cross-sectional associations of
severe hypoglycaemia with cognitive status, brain volumes and prior 15 year
cognitive decline. We also conducted a prospective survival analysis of incident
dementia from baseline, visit 4 (1996-1998), to 31 December 2013. Severe
hypoglycaemia was identified, using ICD-9 codes, from hospitalisations, emergency
department visits and ambulance records. Prior cognitive decline was defined as
change in neuropsychological test scores from visit 4 (1996-1998) to visit 5
(2011-2013). At visit 5, a subset of participants underwent brain MRIs. Analyses
were adjusted for demographics, APOE genotype, use of diabetes medication,
duration of diabetes and glycaemic control. RESULTS: Among 2001 participants with
diabetes at visit 5 (mean age 76 years), a history of severe hypoglycaemia (3.1%
of participants) was associated with dementia (vs normal cognitive status): OR
2.34 (95% CI 1.04, 5.27). In the subset of participants who had undergone brain
MRI (n = 580), hypoglycaemia was associated with smaller total brain volume (
0.308 SD, 95% CI -0.612, -0.004). Hypoglycaemia was nominally associated with a
15 year cognitive change (-0.14 SD, 95% CI -0.34, 0.06). In prospective analysis
(n = 1263), hypoglycaemia was strongly associated with incident dementia (HR
2.54, 95% CI 1.78, 3.63). CONCLUSIONS/INTERPRETATION: Our results demonstrate a
strong link between severe hypoglycaemia and poor cognitive outcomes, suggesting
a need for discussion of appropriate diabetes treatments for high-risk older
adults.
PMID- 29961108
TI - Association between objectively measured built environments and adult physical
activity in Gyeonggi province, Korea.
AB - OBJECTIVES: In the present study, the association between objectively measured
built environments and physical activity (PA) was examined. METHODS: Data were
obtained from the Korean Community Health Survey (KCHS). A total of 82,419
individuals living in 546 neighborhoods of Gyeonggi province were analyzed. Built
environments were measured by geographic information systems (GIS) using Korean
government databases. PA was assessed using the IPAQ-short form. Multilevel
logistic regression was performed. RESULTS: Living in a community with a short
distance to parks was associated with a 42% increased odds of PA; living in a
community with low population density was associated with a 21% decreased odds of
PA. However, most variations in PA were attributed to individual factors.
Additionally, gender-specific correlates associated with PA were observed.
CONCLUSIONS: Although the associations of individual factors with PA were
stronger than of community factors, notably, built environments influenced most
people in a community. Therefore, along with health education and service, policy
makers and planners should consider more parks in less populated areas to create
a supportive environment for PA.
PMID- 29961109
TI - Recovering sexual satisfaction after prolapse surgery: a secondary analysis of
surgical recovery.
AB - INTRODUCTION AND HYPOTHESIS: We compared pre- and postoperative sexual function
scores in sexually active women undergoing pelvic organ prolapse (POP) surgery.
METHODS: Planned secondary analysis of women enrolled in the Restricted
Convalescence: Outcomes Following Urogynecologic Procedures study, a randomized
trial of postoperative activity after POP surgery. All participants could return
to sexual activity at 6 weeks. Participants completed the Pelvic Floor Distress
Inventory (PFDI), the Patient-Reported Outcomes Measurement Information System
(PROMIS) profile, and the Golombok Rust Inventory of Sexual Satisfaction (GRISS)
questionnaires at baseline and 3 months. GRISS is a validated 28-item survey for
heterosexual couples that contains seven subscales to assess sexual function.
Higher scores represent worse sexual function. RESULTS: Thirty-seven sexually
active women were assessed. Mean age +/- standard deviation (SD) was 56 +/- 11,
most of whom (92%) were Caucasian; 78% had undergone minimally invasive
sacrocolpopexy, and the remainder had native tissue vaginal repairs. GRISS scores
improved 3 months after surgery [4.5 +/- 2.6 to 3.6 +/- 2.2, p < 0.001; mean
decrease of 0.9, 95% confidence interval (CI) 0.36-1.36]. PFDI scores improved
from 122 +/- 53 at baseline to 28 +/- 31 at 3 months (p < 0.001). Higher GRISS
scores were correlated with higher PFDI scores (Spearman's rho = 0.35, p = 0.03)
at baseline and 3 months (Spearman's rho = 0.31, p = 0.03). Several GRISS
subscales improved after surgery: partner avoidance (p = 0.01), vaginismus (p =
0.02), noncommunication (p = 0.01), dissatisfaction (p = 0.03), and anorgasmia (p
= 0.001). However, sexual infrequency (p = 0.08) and nonsensuality (p = 0.4) did
not change. Fifty-one percent had sexual dysfunction before surgery, which
decreased to 32% after surgery (p = 0.04). CONCLUSION: Sexual function and
satisfaction are significantly improved 3 months following POP surgery. Improved
sexual function is correlated with improved pelvic floor symptoms.
PMID- 29961111
TI - In vivo assessment of the levator ani muscles using shear wave elastography: a
feasibility study in women.
AB - INTRODUCTION AND HYPOTHESIS: We hypothesized that shear wave elastography (SWE)
technology might be useful for assessing the elastic properties of the pelvic
floor in women. Our primary objective was to evaluate the feasibility of
assessing the levator ani muscles using SWE in women. Our secondary aim was to
investigate the changes in their elastic properties from rest to Valsalva
maneuver. METHODS: During this prospective feasibility study in nonpregnant
female volunteers, we collected data on participant age, body mass index (BMI),
parity, and time since the delivery. The levator ani muscles of each participant
were assessed using SWE technology at rest and during a Valsalva maneuver by
measuring the shear modulus (in kilopascals). We then assessed the changes in the
shear modulus at rest and during the Valsalva maneuver using a Wilcoxon test.
RESULTS: Twelve parous women participated in this study. The mean time since the
last delivery was 14 months, the mean age was 31 years, and mean BMI was 28 kg.m
2. All the assessments performed at rest were successfully completed, but we
encountered two failures during the Valsalva maneuver. The mean shear modulus
increased by a factor of more than 2 from rest to the Valsalva maneuver for both
the right (16.0 vs 35.4 kPa) and left side (17.1 vs 37.6 kPa). CONCLUSIONS: An
assessment of the elastic properties of the levator ani muscles is feasible for
nonpregnant women. The reproducibility of the technique and its application in
pregnant women and women with pelvic floor disorders must be investigated.
PMID- 29961110
TI - RCT of vaginal extraperitoneal uterosacral ligament suspension (VEULS) with
anterior mesh versus sacrocolpopexy: 4-year outcome.
AB - INTRODUCTION AND HYPOTHESIS: This study assessed the safety and efficacy of
vaginal extraperitoneal uterosacral ligament suspension (VEULS) with anterior
overlay mesh versus sacrocolpopexy (SCP) for posthysterectomy vault prolapse.
METHODS: This was a multicenter randomized trial of women with posthysterectomy
vault prolapse stage >2 according to the Pelvic Organ Prolapse Quantification
(POP-Q) system. Primary outcome was a composite of no vaginal bulge symptoms, no
anatomical recurrence in the anterior or apical compartment at or beyond the
hymenal ring, and no surgical retreatment for prolapse 12 months postsurgery.
Secondary outcomes were peri- and postoperative complications, changes in
prolapse, and urogenital and sexual symptoms at 12, 24, and 48 months based on
the Pelvic Floor Distress Inventory (PFDI)-20. RESULTS: Between 2006 and 2011, 82
eligible women were randomized: 39 received VEULS and 43 received SCP. Primary
composite outcome at 12 months for success was 41% for VEULS and 65% for SCP
[odds ratio (OR 2.68, p = 0.03)]. Perioperative complications were more common in
the SCP group. C-point was higher for SCP (-6.0 VEULS vs -8.0 SCP, p = 0.005) and
total vaginal length (TVL) was longer for SCP (8.0 VEULS vs 9.0 SCP, p = 0.05).
Cumulative mesh exposure rate at 4 years was similar between the uterosacral
[4/39 (10.3%)] and sacrocolpopexy [4/43 (9.3%)] groups, bearing in mind that not
all patients were examined at 4 years. Subjective outcomes derived from three
domains of the PFDI-20 were similar at 12, 24, 48 months. Postoperative Pelvic
Organ Prolapse Distress Inventory (POPDI) score improved similarly for both
groups at all timepoints, with the minimally important difference of at least 21
reached for both groups. CONCLUSIONS: Composite outcome of success was better for
SCP at 12 months, but subjective outcomes for prolapse at all timepoints over 4
years for VEULS and SCP were not significantly different.
PMID- 29961112
TI - The Female Genital Self-Image Scale (FGSIS): cross-cultural adaptation and
validation of psychometric properties within a Turkish population.
AB - INTRODUCTION AND HYPOTHESIS: Women's perceived satisfaction from their own
genital appearance is linked to genital image and sexual esteem. A comprehensive
and easy to use scale to measure self-image was scarce in the literature. It was
aimed in the present study to complement cross-culturally adapted and validated
into Turkish version of the Female Genital Self-Image Scale (FGSIS) and to assess
its psychometric properties. METHODS: After cross-cultural adaptation, the
Turkish version of the FGSI, Female Sexual Distress Scale-Revised (FSDS-R), and
Female Sexual Function Index (FSFI) were administered to 461 female participants.
Content/face validity, exploratory, and confirmatory factor analysis, internal
consistency, and reliability were appropriately assessed. Predefined and specific
hypotheses were formulated for construct validity. RESULTS: Our findings
indicated excellent content/face validity, sufficient internal consistency
(Cronbach's alpha 0.818), and test-retest reliability [intraclass correlation
coefficient (ICC) 0.951]. Construct validity was demonstrated by proving the
hypothesis that participants who have performed at least one vaginal/clitoral
masturbation for the last month reported significantly higher FGSIS scores
compared with those who abstained (Z -6.37, p < 0.001). Factor analyses formed
one factor structure. In the proposed two-factor construct, all seven items
demonstrated good to high correlations with their subdomains and lower
correlations with the other domain, indicating sufficient convergent validity.
CONCLUSIONS: The FGSIS was successfully validated for use in the Turkish
population. The scale exhibited strong psychometric properties to assess
perceived female genital image. It might be reliably used in genital cosmetic
surgeries and in a variety of gynecologic conditions.
PMID- 29961113
TI - Uterus preservation is superior to hysterectomy when performing laparoscopic
lateral suspension with mesh.
AB - INTRODUCTION AND HYPOTHESIS: We aimed to compare differences between laparoscopic
lateral suspension with mesh (LLS) performed with supracervical hysterectomy
(LLSHE) and without hysterectomy (LLSUP). METHODS: We retrospectively collected
data from women operated by a single surgeon between 2003 and 2011. From a total
of 339 women with symptomatic anterior and/or apical pelvic organ prolapse (POP)
and an intact uterus, 224 had LLSUP (70.4%) and 94 had LLSHE (29.6%). Three
hundred and sixteen patients were examined at 1 year. Primary outcomes were
objective and subjective success at 1 year during clinical evaluation. Secondary
outcomes were complications (Clavien-Dindo scale) and mesh exposure. Patient
satisfaction was evaluated by telephone interview using a 10-point scale and the
Patient Global Impression of Improvement Scale (PGI-I). RESULTS: LLSUP and LLSHE
did not differ for age (mean 57 and 55 years, respectively), preoperative status,
complications, and participation at the interview (52 vs 53%). LLSHE is
associated with higher mesh exposure (6.5 vs 1.3%, p = 0.014) and more frequent
use of Mersilene. Titanium-coated and noncoated polypropylene was more frequently
used in LLSUP. At 1 year, both anatomic success rate for the anterior compartment
(98.7 vs 94.6%, p = 0.021) and subjective success rate (83.5 vs 72.8%, p = 0.035)
were higher for LLSUP. Without hysterectomy, patients more often improved (90.5
vs 76.5%, p = 0.013) and would more frequently recommend the procedure (94.5 vs
80.4%, p = 0.004). CONCLUSIONS: LLS with or without hysterectomy is a safe
technique with high patient satisfaction. The uterus-preserving approach appears
to result in better anatomic outcome for the anterior compartment, better
subjective outcome, and higher patient satisfaction.
PMID- 29961114
TI - Completion of a validated pelvic floor symptom and bother instrument in real-life
practice.
AB - INTRODUCTION AND HYPOTHESIS: Validated questionnaires are commonly used in
research, but successful completion rates in clinical settings are largely
unknown. The primary goal of this study was to assess the frequency of
appropriate completion of a validated research survey. We secondarily examined
relationships between demographics and successful questionnaire completion.
METHODS: New patients completed a paper form of the Pelvic Floor Bother
Questionnaire (PFBQ) to assess pelvic floor symptoms and level of bother. Various
aspects of successful survey completion were assessed, including unanswered
questions, affirmative responses without selection of a level of bother, or
choosing a level of bother despite reporting not having a symptom. Relationships
between self-reported demographic characteristics and completion of the survey
were also evaluated. RESULTS: Five hundred and fourteen questionnaires were
completed by a cohort of women with a mean age of 57.5 +/- 14.4 years (range 19
97). Overall, 45.3% of women (n = 233) completed the entire PFBQ properly as
originally described. Women skipped at least one entire question 16.5% of the
time. On logistic regression, older age was significantly associated with
improper questionnaire completion (55.0 years +/-14.9 successful vs 59.6 years +/
13.6 unsuccessful completion, p < 0.001 for overall completion). Age was
significantly associated with proper completion of every individual PFBQ
question, except question 8 concerning fecal incontinence (p = 0.06). Education
level was not significantly associated with successful questionnaire completion.
CONCLUSIONS: Overall successful completion of the survey as designed and
validated was low, even in a highly educated population. Ways to simplify the
instrument to enhance completion, such as electronic smart questionnaires, should
be further investigated.
PMID- 29961115
TI - Impact of lifetime compared to adolescent-onset mental illness on psychosocial
employment quality in adulthood: analysis of a nationally representative French
cohort.
AB - PURPOSE: We investigated prospective associations between mental illness and
psychosocial employment quality using a nationally representative sample of the
French working population by gender, primary diagnosis, and age of onset.
METHODS: 6234 employed French adults (aged 20-74 years) were followed from 2006
to 2010. All respondents provided data on 26 indicators of psychosocial
employment quality drawn from the Job-Strain Model, other job stressors, and
indicators of working time stressors (i.e., shift work, night work, and long
working hours). RESULTS: We performed 272 statistical tests, of which 37 were
significant following adjustment for age, poor socio-economic position during
childhood, unemployment status at wave one, and anxiety or depression at wave
two. Females with a lifetime diagnosis of any mental illness reported higher
psychological and emotional demands at work, whilst males reported low decision
latitude, tensions with the public, and work-life imbalance. In both genders a
lifetime diagnosis of any mental illness was associated with role and ethical
conflict. A lifetime diagnosis of major depression appeared to have stronger
associations for females, whilst substance use disorder was associated with
poorer psychosocial employment quality in males. Adolescent-onset mental illness
might be associated with poorer psychosocial employment quality among men more so
than among women. CONCLUSIONS: Results suggest that people with a history of
mental illness who obtain employment tend to be employed in jobs characterized by
poor psychosocial quality. Employment quality should be considered in vocational
rehabilitation policies and practices aimed at optimizing employment
participation in this population.
PMID- 29961116
TI - A fuzzy multi-stakeholder multi-criteria methodology for water allocation and
reuse in metropolitan areas.
AB - In this paper, a fuzzy decision making methodology is proposed to find a socially
optimal scenario for allocating effluent of wastewater treatment plants and urban
and suburban runoffs to agricultural regions and recharging aquifers. The
presented methodology named modified fuzzy social choice (MFSC) considers multi
stakeholder multi-criteria problems under uncertainties inherent in a decision
making process utilizing a fuzzy ranking method and the fuzzy social choice (FSC)
theory. A set of water and wastewater allocation scenarios are proposed for water
quantity and quality management of the study area, while six main stakeholders
with conflicting utilities and different negotiation powers are involved. The
proposed methodology is applied to Tehran metropolitan area, the capital city of
Iran with the population of about 8 million people, to examine its applicability
and effectiveness. The results shows that using fuzzy multi-stakeholder multi
criteria decision making method considering equal and different negotiation
powers can lead to different outcomes. Based on the results, the MFSC method,
which considers a number of decision makers having different negotiation powers,
degrees of importance of decision making criteria, and some important
uncertainties, performs more promising in real water resources management
problems.
PMID- 29961117
TI - Retrospective analysis of primarily treated group D retinoblastoma.
AB - PURPOSE: To assess the effectiveness of intra-arterial chemotherapy (IAC),
intravenous chemotherapy (IVC), and their combination in the management of group
D retinoblastoma. METHODS: This was a retrospective, interventional, comparative,
and non-randomized clinical study, including all eyes with primarily treated
group D retinoblastoma managed in a single institution from February 2010 to July
2016. Patient demographics, treatment modality (primary enucleation, intravenous
chemotherapy, intra-arterial chemotherapy alone or intravenous, and intra
arterial chemotherapy), additional need for consolidation treatments or
intravitreal melphalan (IVM) injections, and follow-up time were recorded. The
main outcome measure was ocular survival rate after various treatment modalities.
RESULTS: Of 87 eyes of 83 consecutive cases, 9 eyes (10.3%) were primarily
enucleated, 37 (42.6%) eyes received IVC, 30 (34.5%) eyes had IAC, and 11 (12.6%)
eyes were treated with IVC followed by IAC. After a mean 81.1 +/- 75.2 weeks of
follow-up, enucleation rates were 56.8% in the IVC group, 23.3% in the IAC group,
and 36.6% in the IVC + IAC group (p = 0.021). There was no significant difference
of ocular survival estimates among these 3 groups at 2 or 5 years (p = 0.998, p =
0.986). With logistic regression analysis, age; gender; disease laterality;
administration of IVM, TTT, or cryotherapy; mean dose of IVM; follow-up time; and
number of IAC or IVC cycles were not significantly related to the enucleation
rate (p > 0.05 for all variables). CONCLUSIONS: Our experience showed that in
group D patients, primary IAC achieved ocular survival in 76.7% of eyes, and less
need for local consolidation treatments, whereas following primary IVC ocular
survival was 43.2%.
PMID- 29961118
TI - Prevalence of naturally occurring amino acid substitutions associated with
resistance to hepatitis C virus NS3/NS4A protease inhibitors in Sao Paulo state.
AB - Hepatitis C (HCV)-infected patients are treated with direct-acting antiviral
agents (DAAs) in highly effective, well-tolerated, all-oral regimens. However,
naturally occurring resistance-associated amino acid substitutions (RASs) may be
selected during treatment. This study aimed to screen naturally occurring RASs
NS3/NS4A inhibitors (PIs). Samples were obtained from DAA naive patients, living
in Sao Paulo state, Brazil. Screening for RASs in the HCV NS3 region was
conducted in 859 samples from HCV-infected patients, of which 425 and 434 samples
were subtype 1a and 1b, respectively. HCV-RNA was extracted, amplified, and
sequenced. The overall prevalence of RASs to HCV PIs was 9.4%. The following RASs
were observed in HCV-1a subtype infected patients: V36L (2.6%), T54S (1.6%),
V55I/A (1.2% / 8.9%, respectively), Q80K (2.1%), R155K (0.5%), and D168E (0.2%);
and in HCV-1b infected patients: V36L (0.7%), T54A/S (0.2% and 0.5%,
respectively), V55A (0.5%), Q80K (0.2%), D168E (1.6%), and M175L (0.5%). HCV 1a
infected subjects had higher serum viral load than that seen in patients infected
with HCV 1b. There was no difference between the proportions of NS3 RASs with
regards to geographic distribution within the investigated areas. These findings
should be supported by additional studies in Brazil to help in the formation of
local clinical guidelines for managing hepatitis C.
PMID- 29961119
TI - Clinical evaluation of a panel of multiplex quantitative real-time reverse
transcription polymerase chain reaction assays for the detection of 16
respiratory viruses associated with community-acquired pneumonia.
AB - We developed a panel of multiplex quantitative real-time reverse transcription
polymerase chain reaction (mqRT-PCR) assay consisting of seven internally
controlled qRT-PCR assays to detect 16 different respiratory viruses. We compared
the new mqRT-PCR with a previously reported two-tube mRT-PCR assay using 363
clinical sputum specimens. The mqRT-PCR assay performed comparably with the two
tube assay for most viruses, offering the advantages of quantitative analysis,
easier performance, lower susceptibility to contamination, and shorter turnaround
time in laboratories equipped with conventional real-time PCR instrumentation,
and it could therefore be a valuable tool for routine surveillance of respiratory
virus infections in China.
PMID- 29961120
TI - Titanium dioxide nanoparticles impaired both photochemical and non-photochemical
phases of photosynthesis in wheat.
AB - Titanium dioxide nanoparticles (TiO2-NP) are increasingly being proposed for
nanoagriculture but their effect on photosynthesis is limited and contradictory,
mostly regarding putative chronical effects associated to the exposure to the
commercial P25 formulation (anatase:rutile). This research aims at evaluating how
chronical exposure to P25-NP affect photosynthetic processes in Triticum
aestivum. Wheat plants were exposed (from the germination stage) to 0, 5, 50, and
150 mg L-1 P25-NP for 20 days. P25-NP impaired both light-dependent and
independent phases of photosynthesis, decreased chlorophyll a content, maximal
and effective efficiency of PSII, net photosynthetic rate, transpiration rate,
stomatal conductance, intercellular CO2 concentration, and starch content. On the
other hand, no effects were observed in photochemical and in non-photochemical
quenching values, on total soluble sugar (TSS) content or in RuBisCO activity.
Our results support that the induced decay in chlorophyll a content compromised
the electron transport through PSII and that stomatal limitations impaired CO2
assimilation. The decline of starch content seems to be a consequence of its
degradation as a mechanism to maintain the TSS levels. Consequently, we propose
that photosynthetic related endpoints are sensitive and valuable biomarkers to
assess TiO2-NP toxicity.
PMID- 29961121
TI - Selective, fast and semi-automatic enrichment of nucleosides by using a
phenylboronic acid modified hybrid material composed of graphene oxide and
melamine sponge.
AB - A hybrid material was prepared from graphene oxide and melamine sponge, and
modified with phenylboronic acid to obtain a sorbent for the enrichment of the
nucleosides cytidine, uridine, inosine, guanosine and adenosine. The loading
capacity typically is around 27.8 mg g-1 which is comparable to other sorbents,
and highly selectivity for cis-diols is observed even if the concentration of
potential interferents is 1500-fold higher. The sorbent was placed in an
injector, and the process was operated semiautomatically by using a peristaltic
pump. The sorbent is stable and can be re-used six times without decrease in
efficiency. It was applied to the selective extraction of the cis-diols
(cytidine, uridine, inosine, guanosine, adenosine) from HepG2 cells. It presents
good linear between 3 to 5000 MUg L-1 and the limits of detection (in HPLC
analysis with UV detection) are 1-4 MUg L-1. Good recoveries of 85-101% were
obtained with spiked HepG2 cells samples, with relative standard deviation of
<=9.9%. Graphical abstract Schematic for the preparation of boronic acid modified
graphene oxide/melamine sponge composite for in-syringe solid-phase extraction of
nucleosides.
PMID- 29961122
TI - Olfactory navigation versus olfactory activation: a controversy revisited.
AB - In the early 1970s, Floriano Papi and colleagues proposed the olfactory
navigation hypothesis, which explains the homing ability of pigeons by the
existence of an odor-based map acquired through learning. This notion, although
supported by some observations, has also generated considerable controversy since
its inception. As an alternative, Paulo Jorge and colleagues formulated in 2009
the olfactory-activation hypothesis, which states that atmospheric odorants do
not provide navigational information but, instead, activate a non-olfactory path
integration system. However, this hypothesis is challenged by an investigation
authored by Anna Gagliardo and colleagues and published in the current issue of
the Journal of Comparative Physiology A. In this editorial, the significance of
the findings of this study is assessed in the broader context of the role of
olfaction in avian navigation and homing, and experiments are suggested that
might help to finally resolve the olfactory-navigation versus olfactory
activation controversy.
PMID- 29961123
TI - Poly(amidoamine)-alginate hydrogels: directing the behavior of mesenchymal stem
cells with charged hydrogel surfaces.
AB - The surface charge of a biomaterial represents a promising tool to direct
cellular behavior, which is crucial for therapeutic approaches in regenerative
medicine. To expand the understanding of how the material surface charge affects
protein adsorption and mesenchymal stem cell behavior, differently charged
surfaces with zeta potentials spanning from -25 mV to +15 mV were fabricated by
the conjugation of poly(amidoamine) to alginate-based hydrogels. We showed that
the increase of the biomaterials surface charge resulted in enhanced quantities
of biologically available, surface-attached proteins. Since different surface
charges were equalized after protein adsorption, mesenchymal stem cells
interacted rather with diverse protein compositions instead of different surface
features. Besides an enhanced cell attachment to increasingly positively charged
surfaces, the cell spreading area and the expression of adhesion-related genes
integrin alpha5 and tensin 1 were found to be increased after adhesion. Moreover,
first results indicate a potential impact of the surface charge on mesenchymal
stem cell differentiation towards bone and fat cells. The improved understanding
of surface charge-related cell behavior has significant impact on the design of
biomedical devices and artificial organs.
PMID- 29961126
TI - External neurolysis as a treatment for foot drop secondary to weight loss: a
retrospective analysis of 200 cases.
AB - BACKGROUND: Peroneal nerve entrapment is the most common peripheral
mononeuropathy of the lower limbs. Foot drop, a common presentation, leads to an
impaired eversion and dorsiflexion of the foot. An intriguing observation is the
occurrence of foot drop secondary to weight loss. METHODS: A retrospective study
of patients surgically treated for peroneal nerve entrapment was performed
between January 1, 1995 and December 31, 2016, at the Department of Neurosurgery,
Genk, Belgium. Out of a total of 421 patients, 200 patients with foot drop
secondary to weight loss were included. For each subject, motor and sensory
outcomes after external neurolysis were investigated. As a primary objective, we
examined the postoperative outcomes of external neurolysis as a treatment for
foot drop in patients with peroneal nerve entrapment at the fibular head
secondary to weight loss. As a secondary objective, we analyzed the correlation
between patient characteristics and the success rate of external neurolysis.
RESULTS: When defining success as a postoperative MRC score of 4 or 5, external
neurolysis has a success rate of 85% in patients with foot drop secondary to
weight loss. A significant difference (P = < 0.0001) between postoperative and
preoperative MRC scores indicates that external neurolysis leads to significant
improvement of motor function in patients with foot drop secondary to weight
loss. A multiple logistic regression model showed that "preoperative MRC scores"
and "duration of symptoms" were the only variables with an impact on
postoperative MRC scores. Other variables such as "age," "gender," and "side of
entrapment" had no significant impact on postoperative results. CONCLUSIONS:
Statistical analysis emphasizes the important role of external neurolysis in the
treatment of peripheral peroneal nerve entrapment. Therefore, external neurolysis
at the fibular head should be regarded as a very effective and safe procedure in
patients with foot drop secondary to weight loss.
PMID- 29961125
TI - Predictors of early progression of surgically treated atypical meningiomas.
AB - BACKGROUND: Clinical behaviour of atypical meningiomas is not uniform. While, as
a group, they exhibit a high recurrence rate, some pursue a more benign course,
whereas others progress early. We aim to investigate the imaging and pathological
factors that predict risk of early tumour progression and to determine whether
early progression is related to outcome. METHODS: Adult patients with WHO grade
II meningioma treated in three regional referral centres between 2007 and 2014
were included. MRI and pathology characteristics were assessed. Gross total
resection (GTR) was defined as Simpson 1-3. Recurrence was classified into early
and late (<= 24 vs. > 24 months). RESULTS: Among the 220 cases, 37 (16.8%)
patients progressed within 24 months of operation. Independent predictors of
early progression were subtotal resection (STR) (p = 0.005),
parafalcine/parasagittal location (p = 0.015), peritumoural oedema (p = 0.027)
and mitotic index (MI) > 7 (p = 0.007). Adjuvant radiotherapy was negatively
associated with early recurrence (p = 0.046). Thirty-two per cent of patients
with residual tumour and 26% after GTR received adjuvant radiotherapy. There was
a significantly lower proportion of favourable outcomes at last follow-up (mRS 0
1) in patients with early recurrence (p = 0.001). CONCLUSIONS: Atypical
meningiomas are a heterogeneous group of tumours with 16.8% patients having
recurrence within 24 months of surgery. Residual tumour, parafalcine/parasagittal
location, peritumoural oedema and a MI > 7 were all independently associated with
early recurrence. As administration of adjuvant radiotherapy was not protocolised
in this cohort, any conclusions about benefits of irradiation of WHO grade II
meningiomas should be viewed with caution. Patients with early recurrence had
worse neurological outcome. While histological and imaging characteristics
provide some prognostic value, further molecular characterisation of atypical
meningiomas is warranted to aid clinical decision making.
PMID- 29961127
TI - Hyponatremia: a new predictor of mortality in patients with Shiga toxin-producing
Escherichia coli hemolytic uremic syndrome.
AB - OBJECTIVES: (1) Evaluate mortality rate in patients with Shiga toxin-producing
Escherichia coli hemolytic uremic syndrome, (2) determine the leading causes of
death, and (3) identify predictors of mortality at hospital admission. METHODS:
We conducted a multicentric, observational, retrospective, cross-sectional study.
It included patients under 18 years old with Shiga toxin-producing Escherichia
coli hemolytic uremic syndrome hospitalized between January 2005 and June 2016.
Clinical and laboratory data were obtained from the Argentine National
Epidemiological Surveillance System of Hemolytic Uremic Syndrome. Clinical and
laboratory variables were compared between deceased and non-deceased patients.
Univariate and multivariate analyses were performed. ROC curves and area under
the curve were obtained. RESULTS: Seventeen (3.65%) out of the 466 patients died,
being central nervous system involvement the main cause of death. Predictors of
death were central nervous system involvement, the number of days since the
beginning of diarrhea to hospitalization, hyponatremia, high hemoglobin, high
leukocyte counts, and low bicarbonate concentration on admission. In the
multivariate analysis, central nervous system involvement, sodium concentration,
and hemoglobin were independent predictors. The best cut off for sodium was <=
128 meq/l and for hemoglobin >= 10.8 g/dl. CONCLUSIONS: Mortality was low in
children with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome,
being central nervous system involvement the main cause of death. The best
mortality predictors found were central nervous system involvement, hemoglobin,
and sodium concentration. Hyponatremia may be a new Shiga toxin-producing
Escherichia coli hemolytic uremic syndrome mortality predictor.
PMID- 29961128
TI - Fluorometric aptamer-based determination of ochratoxin A based on the use of
graphene oxide and RNase H-aided amplification.
AB - The authors describe a fluorometric assay for ochratoxin A (OTA) that is based on
the use of graphene oxide and RNase H-aided amplification. On addition of OTA,
cAPT is replaced from the APT/cAPT hybridization complex and then hybridizes with
RNA labeled with a fluorophore at the 5'-end. Eventually, the fluorophore is
released by RNase H cleavage. As the concentration of OTA increases, more cAPTs
are displaced, this leading to fluorescence enhancement (best measured at
excitation/emission wavelengths of 495/515 nm). This RNase H-assisted cycle
response results in strong signal amplification. The limit of detection,
calculated on the basis of a signal to noise ratio of 3, is 0.08 ng.mL-1.
Response is linear in the 0.08-200 ng.mL-1 OTA concentration range. The method is
highly selective for OTA over ochratoxin B and aflatoxin B1. It was applied to
the determination of OTA in red wine samples spiked at levels of 1, 7, and 50
ng.mL-1, and the recoveries ranged from 90.9 to 112%. Graphical abstract
Schematic of a novel fluorometric aptasensor for ochratoxin A based on the use of
graphene oxide and RNase H-aided amplification.
PMID- 29961130
TI - Endoscopic diagnosis and treatment of esophageal adenocarcinoma: introduction of
Japan Esophageal Society classification of Barrett's esophagus.
AB - Endoscopic surveillance of Barrett's esophagus has become a foundation of the
management of esophageal adenocarcinoma (EAC). Surveillance for Barrett's
esophagus commonly involves periodic upper endoscopy with biopsies of suspicious
areas and random four-quadrant biopsies. However, targeted biopsies using narrow
band imaging can detect more dysplastic areas and thus reduce the number of
biopsies required. Several specific mucosal and vascular patterns characteristic
of Barrett's esophagus have been described, but the proposed criteria are complex
and diverse. Simpler classifications have recently been developed focusing on the
differentiation between dysplasia and non-dysplasia. These include the Japan
Esophageal Society classification, which defines regular and irregular patterns
in terms of mucosal and vascular shapes. Cancer invasion depth is diagnosed by
endoscopic ultrasonography (EUS); however, a meta-analysis of EUS staging of
superficial EAC showed favorable pooled values for mucosal cancer staging, but
unsatisfactory diagnostic results for EAC at the esophagogastric junction.
Endoscopic resection has recently been suggested as a more accurate staging
modality for superficial gastrointestinal cancers than EUS. Following endoscopic
resection for gastrointestinal cancers, the risk of metastasis can be evaluated
based on the histology of the resected specimen. European guidelines describe
endoscopic resection as curative for well- or moderately differentiated mucosal
cancers without lymphovascular invasion, and these criteria might be extended to
lesions invading the submucosa (<= 500 MUm), i.e., to low-risk, well- or
moderately differentiated tumors without lymphovascular involvement, and < 3 cm.
These criteria were confirmed by a recent study in Japan.
PMID- 29961129
TI - Large elevation and small host plant differences in the arbuscular mycorrhizal
communities of montane and alpine grasslands on the Tibetan Plateau.
AB - Understanding the diversity and community structure of arbuscular mycorrhizal
fungi (AMF) in extreme conditions is fundamental to predict the occurrence and
evolution of either symbiotic partner in alpine ecosystems. We investigated the
AMF associations of three plant species at elevations ranging between 3105 and
4556 m a.s.l. on Mount Segrila on the Tibetan Plateau. Three of four locations
were studied in two consecutive years. The AMF diversity and community
composition in the roots of Carex pseudofoetida, Pennisetum centrasiaticum, and
Fragaria moupinensis differed little. However, at high elevations, the abundance
of members of Acaulosporaceae increased relative to that of Glomeraceae. Plants
at lower elevation sites, where Glomeraceae predominated as root symbionts, had
higher leaf nitrogen and phosphorus concentrations than plants at higher
elevation sites, where Acaulosporaceae predominated. The overall phylogenetic
relatedness of the AMF increased with increasing elevation. This suggests that
abiotic filtering may play an important role in the structuring of symbiotic AMF
communities along elevational gradients. The functional role of Acaulosporaceae
whose relative abundance was found to increase with elevation in alpine
environments needs to be clarified in future studies.
PMID- 29961131
TI - Photographic comparison: a method for qualitative outdoor thermal perception
surveys.
AB - This article addresses the use of photographic comparison as a complementary
visual appraisal method in an outdoor thermal perception survey. This survey was
carried out during a Ph.D. research exploring how materials and vegetation
influence thermal comfort in outdoor public spaces. Objective and subjective
thermal perception parameters were combined and quantitative and qualitative
research methods were used. The quantitative methods included microclimatic
measurements, whilst the qualitative methods comprised observations and spatially
localised interviews based on a questionnaire and the photographic comparison.
This article explores how such visual research method allowed triangulating
findings of this field survey. Three non-edited photographs of outdoor public
spaces, under similar summer meteorological conditions but with contrasting
spatial features, were shown to respondents to the questionnaire. The photographs
depicted undisclosed locations for preventing biased emotional appreciations.
Respondents were asked to select the potentially most comfortable and
uncomfortable environments depicted. The choice of photographs matched the
previous answers on the thermal sensation and evaluation judgement scales. Hence,
we discuss the way the visual interpretations by respondents allowed the
triangulation of in situ thermal perception data. The extent to which thermal
comfort can be interpreted from thermal environments depicted in photographs
containing clear visual signs is further discussed. The article concludes on how
such a visual appraisal method can be valuable for enriching future qualitative
outdoor thermal perception surveys with subjective interpretation of visual data.
PMID- 29961124
TI - Neurotrophic factors and neuroplasticity pathways in the pathophysiology and
treatment of depression.
AB - Depression is a major health problem with a high prevalence and a heavy
socioeconomic burden in western societies. It is associated with atrophy and
impaired functioning of cortico-limbic regions involved in mood and emotion
regulation. It has been suggested that alterations in neurotrophins underlie
impaired neuroplasticity, which may be causally related to the development and
course of depression. Accordingly, mounting evidence suggests that antidepressant
treatment may exert its beneficial effects by enhancing trophic signaling on
neuronal and synaptic plasticity. However, current antidepressants still show a
delayed onset of action, as well as lack of efficacy. Hence, a deeper
understanding of the molecular and cellular mechanisms involved in the
pathophysiology of depression, as well as in the action of antidepressants, might
provide further insight to drive the development of novel fast-acting and more
effective therapies. Here, we summarize the current literature on the involvement
of neurotrophic factors in the pathophysiology and treatment of depression.
Further, we advocate that future development of antidepressants should be based
on the neurotrophin theory.
PMID- 29961132
TI - Three-dimensional modeling of removal torque and fracture progression around
implants.
AB - In the present study, a model for simulations of removal torque experiments was
developed using finite element method. The interfacial retention and fracturing
of the surrounding material caused by the surface features during torque was
analyzed. It was hypothesized that the progression of removal torque and the
phases identified in the torque response plot represents sequential fractures at
the interface. The 3-dimensional finite element model fairly accurately predicts
the torque required to break the fixation of acid-etched implants, and also
provides insight to how sequential fractures progress downwards along the implant
side.
PMID- 29961133
TI - Clinical manifestations and radiological characteristics in patients with
idiopathic syringomyelia and scoliosis.
AB - PURPOSE: To clarify the clinical manifestation and radiological characteristics
of idiopathic syringomyelia (IS) and to investigate the relationship between
syrinx and scoliotic curves in IS-related scoliosis patients. METHODS: Fifty-five
patients with IS and scoliosis were identified and reviewed retrospectively from
June 2009 to December 2016. Radiographic features of syrinx, scoliosis and
clinical manifestations of neurological deficits were collected. The syrinx/cord
(S/C) ratio was defined as the anteroposterior diameter of syrinx divided by the
diameter of spinal cord at the same level. Patients were classified into two
groups, the thoracic group (T group, apex vertebra located from T2 to
intervertebral disk of T11-T12) and the thoracolumbar/lumbar group (TL/L group,
apex vertebra located from T12 to L5). RESULTS: There was no correlation between
the radiological features of idiopathic syrinx and scoliotic curve parameters.
The TL/L group had a lower level of most caudal extent (13.7 compared with 10.6,
P = 0.029) and lower level of largest S/C ratio (12.0 compared with 8.7, P =
0.016) than that in T group. The deviated side of syrinx was not coincident with
major curve convexity (27.2% concordance rate, P = 0.522) or dominant side of
neurological deficit (16.3% concordance rate, P = 0.212). CONCLUSIONS: Patients
with major curves located on the thoracolumbar or lumbar spine had a much lower
caudal extent and lower level of greatest S/C ratio compared to patients with
major curves located on the thoracic spine. No significant relationships were
detected between syrinx features, scoliotic curve parameters and neurological
deficits. These slides can be retrieved under Electronic Supplementary Material.
PMID- 29961134
TI - Updated Guidelines for the Treatment of Acquired Aplastic Anemia in Children.
AB - PURPOSE OF REVIEW: This review aimed to provide updated guidelines for the
management of children with acquired aplastic anemia (AA), particularly focusing
on hematopoietic stem cell transplantation (HSCT). RECENT FINDINGS: Failure-free
survival for children with aplastic anemia has been shown to be better after bone
marrow transplantation (BMT) from matched or one-locus mismatched related donors
(MRD/1MMRD) than after immunosuppressive therapy (IST). A combination of the
absence of minor paroxysmal nocturnal hemoglobinuria clones and short telomere
length was identified as a strong predictor of a poor response to IST. Upfront
HSCT from matched unrelated donors (MUD) and MRD was recently demonstrated to
have comparable outcomes. Moreover, unrelated cord blood transplantation (UCBT)
and haploidentical HSCT have shown promising outcomes, and the
fludarabine/melphalan-based regimen has resulted in excellent survival without
poor graft function. BMT from MRD/1MMRD is the treatment of choice. When a
MRD/1MMRD is not available, upfront BMT from a MUD should be considered for
patients with only a slim chance of responding to IST. UCBT and haploidentical
HSCT are promising options. This updated treatment algorithm should improve
overall outcomes for children with AA.
PMID- 29961135
TI - The effect of the systematic birth preparation program on fear of vaginal
delivery and quality of life.
AB - PURPOSE: The aim of this study was to assess the impact of systematic birth
preparation program on fear of vaginal delivery and quality of life (QoL) in
pregnant women who request elective cesarean delivery without any obstetric
indication. METHODS: This study was conducted prospectively. A total of 100 women
who requested elective cesarean delivery due to psychosocial reasons were
included into the study. Women were divided into two groups according to their
desire to participate in the systematic birth preparation program. Group A: case
group (n = 50) consisted of women who participated in the systematic birth
preparation program. Group B: control group (n = 50) received usual antenatal
care. All patients were interviewed with questionnaires including the World
Health Organization Quality of Life Assessment-BREF (WHOQOL-BREF) and Edinburgh
Postnatal Depression Scale (EPDS) at postpartum 6th week. Type of delivery,
maternal request for cesarean section, scores for QoL, and postpartum depression
were compared between the two groups. RESULTS: Vaginal delivery rate was
significantly higher in among the patients who received the systematic birth
preparation program (group A: 78%, group B: 56%). Maternal request for elective
cesarean section significantly decreased after the systematic birth preparation
program (group A: 8%, group B: 28%). In group A, the WHOQOL-BREF-TR mean scores
(SD) for physical domain, psychological domain, and environmental domain were
significantly higher than the values exhibited in group B. In scores of the
postpartum depression scale, there were no significant differences between the
two groups (p = 0.075). CONCLUSIONS: The current study indicates that systematic
birth preparation program may decrease the rate of elective cesarean delivery by
reducing fear of vaginal delivery and improve the quality of life at postpartum
period.
PMID- 29961136
TI - Levothyroxine use and the risk of breast cancer: a nation-wide population-based
case-control study.
AB - PURPOSE: To investigate whether the use of levothyroxine was associated with
breast cancer risk. METHODS: We conducted a population-based case-control study
in Taiwan. Cases consisted of all patients who were aged 20 years and older, and
had a first-time diagnosis of breast cancer for the period between 2001 and 2011.
The controls were matched to the cases by age, sex, year, and month of diagnosis.
Adjusted odd ratios (ORs) and 95% confidence intervals (CIs) were estimated by a
conditional logistic regression. RESULTS: We examined 65,491 breast cancer cases
and 261,964 controls. We found that use of levothyroxine was associated with a
significant increase in breast cancer risk (OR 1.24, 95% CI 1.15-1.33; P <
0.001). Compared with no use levothyroxine, the adjusted odd ratio was 1.22 (95%
CI 1.11-1.35; P = 0.01) for the group having been prescribed levothyroxine 2
months to 1 year, and 1.26 (95% CI 1.12-1.41; P < 0.01) for the group with more
than 1 year. When stratified by age, the adjusted odd ratio was 1.45 (95% CI 1.23
1.71; P < 0.01) for the patients aged 65 years or more and 1.19 (95% CI 1.09
1.29, P < 0.01) for the patients aged less than 65 years. CONCLUSION: The results
of the present study are the first to suggest that levothyroxine use increased
the risk of breast cancer. However, a larger long-term prospective randomized
controlled trial specifically designed to assess the effect of levothyroxine use
on the risk of developing breast cancer is needed.
PMID- 29961137
TI - Public reporting on cardiac electrophysiology procedures and outcomes: where are
we now and where are we headed?
AB - Over the years, public reporting of patient outcomes has been promoted as a means
to improve healthcare quality. More recently, in response to dramatic rises in
healthcare costs, the Medicare Access and CHIP Reauthorization Act (MACRA) of
2015 was implemented in an effort to link quality with reimbursement. As part of
a value-based model, public reporting of procedural outcomes has been
incorporated into this initiative. Outcomes measures that have been introduced in
cardiology include heart failure readmission and post-myocardial infarction
medication prescription. Public reporting of these data has led not only to
positive changes but also to unintended negative consequences. The limited number
of existing registries and lack of clear consensus on quality metrics have posed
challenges for quality and value assessment in cardiac electrophysiology. After
learning from the lessons of existing models of public reporting, physicians,
professional societies, stakeholders, and patients will need to collaborate to
develop a health care model that can improve outcomes and reduce waste.
PMID- 29961138
TI - Effectiveness of adjunctive hyaluronic acid application in coronally advanced
flap in Miller class I single gingival recession sites: a randomized controlled
clinical trial.
AB - OBJECTIVES: The aim of this randomized controlled clinical trial was to evaluate
the possible advantages of adjunctive hyaluronic acid (HA) application in the
coronally advanced flap (CAF) procedure in single Miller class I/recession type 1
(RT1) gingival recession treatment. MATERIAL AND METHODS: Thirty patients with
one recession were enrolled; 15 were randomly assigned CAF + HA and 15 to CAF
alone. The recession reduction (RecRed), clinical attachment level gain (CAL
gain), changes in probing pocket depth (PPD) and in the width of keratinized
tissue (KT), complete root coverage (CRC), and mean root coverage (MRC) were
calculated after 18 months. Post-operative morbidity (pain intensity, discomfort,
and swelling) was recorded 7 days after treatment using visual analogue scale
(VAS). RESULTS: After 18 months, RecRed was statistically significantly higher in
the test group (2.7 mm [1.0]) than in the control group (1.9 mm [1.0]; p =
0.007). PPD were found to be slightly but statistically significantly increased
in both groups. No statistically significant difference was found for KT gain
between treatments. CRC was 80% for test and 33.3% for control sites (p < 0.05).
A MRC of 93.8 +/- 13.0% for test and 73.1 +/- 20.8% for control sites was
calculated (p < 0.05). The test group reported lower swelling and discomfort
values 7-days post-surgery (p < 0.05). Statistically significant difference was
not found for pain intensity. CONCLUSIONS: The adjunctive use of HA was effective
in obtaining CRC for single Miller class I/RT1 gingival recession sites. CLINICAL
RELEVANCE: Adjunctive application of HA in the coronally advanced flap procedure
may improve the reduction of the recessions and increase the probability of CRC
in Miller class I recessions.
PMID- 29961139
TI - Iodonium salt incorporation in dental adhesives and its relation with degree of
conversion, ultimate tensile strength, cell viability, and oxidative stress.
AB - OBJECTIVE: The aim of this study was to evaluate the degree of conversion,
ultimate tensile strength, cell viability, and oxidative stress of two different
ternary initiation systems, using two photoinitiation polymerization times.
METHODS: The groups investigated were camphorquinone (CQ); CQ and
diphenyleneiodonium hexafluorophosphate (DPI); CQ and ethyl 4-dimethylamine
benzoate (EDAB); and CQ, EDAB, and DPI, with EDAB in high and low concentration.
To assess the degree of conversion (DC) and the ultimate tensile strength (UTS),
a real-time Fourier transform infrared spectroscopy and a universal test machine
Emic DL-500 were used, respectively. Cell viability and oxidative stress were
evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide),
superoxide dismutase (SOD), total sulfhydryl (SH) content, and thiobarbituric
acid reactive species (TBARS) formation assays. RESULTS: Slight lower cell
viability was shown when DPI was associated with high concentrations of EDAB;
this reduction seemed to be attenuated when lower concentrations of EDAB were
used. When EDAB and DPI were associated, no oxidative damage was shown. The
degree of conversion was increased in the ternary systems (CQ + EDAB lower
concentration + DPI) group, which did not affect the UTS, cytotoxicity, and
oxidative stress parameters. The polymerization time did not affect cell
viability, total SH, and TBARS; however, a slight increase was shown in SOD
levels. CLINICAL RELEVANCE: Our study emphasizes the relevance of incorporating
the third element-iodonium salt-in a binary adhesive systems composed exclusively
of CQ and EDAB.
PMID- 29961140
TI - Analysis of blood supply in the hard palate and maxillary tuberosity-clinical
implications for flap design and soft tissue graft harvesting (a human cadaver
study).
AB - OBJECTIVES: The aim of the present study is to provide a detailed macroscopic
mapping of the palatal and tuberal blood supply applying anatomical methods and
studying specific anastomoses to bridge the gap between basic structural and
empirical clinical knowledge. MATERIALS AND METHODS: Ten cadavers (three dentate,
seven edentulous) have been prepared for this study in the Department of Anatomy,
Semmelweis University, Budapest, Hungary, and in the Department of Anatomy of the
Medical University of Graz. All cadavers were fixed with Thiel's solution. For
the macroscopic analysis of the blood vessels supplying the palatal mucosa,
corrosion casting in four cadavers and latex milk injection in other six cadavers
were performed. RESULTS: We recorded major- and secondary branches of the greater
palatine artery (GPA) and its relation to the palatine spine, different
anastomoses with the nasopalatine artery (NPA), and lesser palatal artery (LPA)
as well as with contralateral branches of the GPA. Penetrating intraosseous
branches at the premolar-canine area were also detected. In edentulous patients,
the GPA developed a curvy pathway in the premolar area. The blood supply around
the maxillary tuberosity was also presented. CONCLUSION: The combination of
different staining methods has shed light to findings with relevance to palatal
blood supply, offering a powerful tool for the design and execution of surgical
interventions involving the hard palate. CLINICAL RELEVANCE: The present study
provides clinicians with a good basis to understand the anatomical background of
palatal and tuberal blood supply. This might enable clinicians to design
optimized incision- and flap designs. As a result, the risk of intraoperative
bleeding and postoperative wound healing complications related to impaired blood
supply can be minimized.
PMID- 29961141
TI - Detection of carnosinase-1 in urine of healthy individuals and patients with type
2 diabetes: correlation with albuminuria and renal function.
AB - Low serum carnosinase (CN-1) concentrations are associated with low risk for
development of diabetic nephropathy (DN) in patients with type 2 diabetes (T2D).
Although CN-1 is expressed in the kidney, urinary CN-1 (CNU) excretion and its
pathological relevance in patients with T2D have not been investigated to date.
The present study therefore assessed the extent of CNU excretion in healthy
subjects (n = 243) and in patients with T2D (n = 361) enrolled in the DIAbetes
and LifEstyle Cohort Twente-1 (DIALECT-1) in relation to functional renal
parameters. CNU was detected in a high proportion of healthy individuals, 180
(74%); median CNU excretion was 0.25 mg/24 h [(IQR 0-0.65 mg/24 h]. In patients
with T2D the prevalence and extent of CNU increased in parallel with albuminuria
(r = 0.59, p < 0.0001; median CNU 0.1 vs 0.2 vs 1.5 mg/24 h, p < 0.0001;
prevalence of CNU 61 vs. 81 vs. 97% p < 0.05 in normo- (n = 241), micro- (n = 80)
and macroalbuminuria (n = 40), respectively). Patients with estimated glomerular
filtration rate (eGFR) < 30 ml/min/1.73 m2 displayed higher median CNU excretion
rates in comparison to patients with preserved eGFR (> 90 ml/min/1.73 m2) (1.36
vs 0.13 mg/24 h, p < 0.05). Backward stepwise multivariate linear regression
analysis revealed albuminuria, eGFR and glycosuria to be independent factors of
CNU excretion rates, all together explaining 37% of variation of CNU excretion
rates (R2 = 0.37, p < 0.0001). These results show for the first time that CN-1
can be detected in urine and warrants prospective studies to assess the relevance
of CNU for renal function deterioration in diabetes patients.
PMID- 29961142
TI - Colorimetric chiral recognition of D/L-phenylalanine based on triangular silver
nanoplates.
AB - A new colorimetric analysis approach for chiral recognition of D- and L-forms of
phenylalanine (phe) was developed based on triangular silver nanoplates (TAg
NPs). The TAg-NPs could be used as chiral colorimetric probes for D- and L-forms
of phe. Upon addition of D-phe to TAg-NPs solution, a color change from blue to
purple to pink could be observed, while no obvious color change was found on
addition of L-phe. L-phe could prevent the TAg-NPs from being etched to small
size particles while the protective effect of D-phe was weak. Moreover, the
enantiomeric excess of D-phe could be determined using the proposed chiral assay
in the percentage of L-phe from 0 to 100% with a correlation coefficient of
0.9855. The phenomenon could be monitored by bare eyes and quantified analysis by
UV-Vis spectrophotometry. The developed approach had several advantages, such as
simplicity, visualization, short analysis time and low cost. This study presented
a fast visualization analysis method of chiral D/L-phenylalanine and may lay the
foundation for the development of visualization chiral recognition of other
target analytes.
PMID- 29961143
TI - Maternal L-glutamine supplementation during late gestation alleviates
intrauterine growth restriction-induced intestinal dysfunction in piglets.
AB - Maternal dietary supplementation with L-glutamine (Gln) has been considered as an
option to improve fetal growth and to prevent the occurrence of intrauterine
growth restriction (IUGR). This study investigated whether maternal Gln
supplementation could improve fetal growth as well as the intestinal development
during late pregnancy. Sixty pregnant Landrace * Large White multiparous sows
were assigned to two groups, either the group fed the control diet or the group
with the diet supplemented with 1% Gln from d 85 of gestation until farrowing.
One normal body weight piglet and one IUGR piglet were obtained from six litters
in each group. Reproductive performance, plasma concentrations of free amino
acids and related metabolites as well as piglet growth and tissue indexes were
determined. Maternal Gln supplementation during late gestation increased the
average birth weight, while decreasing the within-litter variation of newborn
piglets. The concentrations of Gln in plasma were lower in IUGR piglets than in
normal piglets. Glutamine supplementation enhanced Gln concentrations in maternal
and piglet plasma and the piglet jejunum, compared with the Control group.
Supplementing Gln suppressed intestinal miR-29a levels, and increased the
abundance of extracellular matrix (ECM) and tight junction (TJ) proteins,
resulting in increased intestinal weight and improved morphologies of the
piglets. Collectively, Gln supplementation to the sow's diet increased fetal
growth, decreased the within-litter variation of newborn piglets, and alleviated
the IUGR-induced intestinal impairment. These findings suggest the possibility of
maternal glutamine supplementation in the prevention and treatment of IUGR in
animal production and human medicine.
PMID- 29961145
TI - Emergency admissions and subsequent inpatient care through an emergency oncology
service at a tertiary cancer centre: service users' experiences and views.
AB - PURPOSE: Avoiding unnecessary emergency admissions and managing those that are
admitted more effectively is a major concern for both patients and health
services. To generate evidence useful for improving services for direct patient
benefit, this study explores service users' views and experiences of emergency
admissions and subsequent inpatient care. METHODS: Participants were recruited
during a cancer-related emergency admission from a tertiary cancer centre with an
emergency oncology service and emergency department. Semi-structured interviews
were conducted with 15 patients and 12 carers post hospital discharge. Interview
transcripts were analyzed using framework analysis. RESULTS: Twenty patients
experienced 43 emergency admissions over 6 months. Most admissions (35/43)
followed patients presenting acutely or as emergencies with cancer treatment side
effects. Most admissions (35/43) were directly to an oncology ward following
specialist advice, review and triage, and thus unavoidable. Participants
experienced outstanding inpatient care because of the following: prompt and
effective symptom control and stabilization of acute conditions; continuity of
cancer care and coordination between acute and long-term treatment; satisfactory
professional-patient communication and information sharing; responsive, motivated
and competent staff; and less restrictive visiting times. Gaps in care were
identified. CONCLUSIONS: Many emergency admissions are necessary for people with
cancer. Future work should focus on improving easy access to specialist advice
and triage, and the process of admission; providing rapid palliation of symptoms
and prompt stabilization of acute conditions, and satisfactory inpatient care;
closing the circle of care for patients by actively involving primary care and
palliative/end-of-life care services to address the complex needs of patients and
carers.
PMID- 29961144
TI - Design and Evaluation of a Real Time Physiological Signals Acquisition System
Implemented in Multi-Operating Rooms for Anesthesia.
AB - With critical importance of medical healthcare, there exist urgent needs for in
depth medical studies that can access and analyze specific physiological signals
to provide theoretical support for practical clinical care. As a consequence,
obtaining the valuable medical data with minimal cost and impacts on hospital
work comes as the first concern of researchers. Anesthesia plays a widely
recognized role in surgeries, which attracts people to undertake relevant
research. In this paper, a real-time physiological medical signal data
acquisition system (PMSDA) for the multi-operating room applications is proposed
with high universality of the hospital practical settings and research
requirements. By utilizing a wireless communication approach, it provides an
easily accessible network platform for collection of physiological medical
signals such as photoplethysmogram (PPG), electrocardiograph (ECG) and
electroencephalogram (EEG) during the surgery. In addition, the raw data is
stored on a server for safe backup and further analysis of depth of anesthesia
(DoA). Results show that the PMSDA exhibits robust, high quality performance and
efficiently reduces costs compared to previously manual methods and allows
seamless integration into hospital environment, independent of its routine work.
Overall, it provides a pragmatic and flexible surgery-data acquisition system
model with low impact and resource cost applicable to research in critical and
practical medical circumstances.
PMID- 29961147
TI - Mitochondrial signalling, physiology and pathophysiology.
PMID- 29961146
TI - The pathophysiology of cancer-related fatigue: current controversies.
AB - Fatigue is one of the most common and debilitating cancer symptoms, and is
associated with impaired quality of life. The exact pathophysiology of cancer
related fatigue (CRF) is poorly understood, but in any individual, it is likely
multifactorial and involves inter-related cytokine, muscular, neurotransmitter,
and neuroendocrine changes. Underlying CRF mechanisms proposed include central
and peripheral hypotheses. Central mechanisms include hypotheses about cytokine
dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm
disruption, serotonin, and vagal afferent nerve function while peripheral
mechanisms include hypotheses about adenosine triphosphate and muscle contractile
properties. Currently, these hypotheses are largely based on evidence from other
conditions in which fatigue is characteristic. The purpose of this article is to
provide a narrative review of the literature and present the current
controversies in the pathophysiology of CRF, particularly in relation to central
and peripheral hypotheses for CRF. An understanding of pathophysiology may
facilitate direct and simple therapeutic interventions for those with cancer.
PMID- 29961148
TI - Natural and synthetic flavonoids, novel blockers of the volume-regulated anion
channels, inhibit endothelial cell proliferation.
AB - Natural flavonoids are ubiquitous in dietary plants and vegetables and have been
proposed to have antiviral, antioxidant, cardiovascular protective, and
anticancer effects. Volume-regulated anion channels (VRACs), which are essential
for cell volume regulation, have been proposed to play a key role in cell
proliferation and migration, apoptosis, transepithelial transport, and cancer
development. In this study, we screened a group of 53 structurally related
natural flavonoids and three synthetic flavonoids for their inhibitory activities
on VRAC currents. A whole-cell patch technique was used to record VRAC currents
in the human embryonic kidney (HEK) 293 and human umbilical vein endothelial
(HUVEC) cells. The 5'-bromo-2-deoxyuridine (BrdU) assay technique was used to
investigate cell proliferation. At 100 MUM, 34 of 53 compounds significantly
inhibited hypotonic extrasolution-induced VRAC currents by > 50% in HEK293 cells.
Among these compounds, luteolin, baicalein, eupatorin, galangin, quercetin,
fisetin, karanjin, Dh-morin, genistein, irisolidone, and prunetin exhibited the
highest efficacy for VRAC blockade (the mean inhibition > 80%) with IC50s of 5-13
MUM and Emaxs of about 87-99%. We also studied the effects of three synthetic
flavonoids on VRAC currents in HEK293 cells. Flavoxate showed high inhibition
efficacy toward VRAC currents (IC50 = 2.3 +/- 0.3 MUM; Emax = 91.8% +/- 2.7%).
Finally, these flavonoids inhibited endogenous VRAC currents and cell
proliferation in endothelial cells. This study demonstrates that natural and
synthetic flavonoids are potent VRAC current inhibitors, and VRAC inhibition by
flavonoids might be responsible for their anti-angiogenic effects.
PMID- 29961149
TI - PGC-1alpha in exercise and fasting-induced regulation of hepatic UPR in mice.
AB - The aim of the present study was to test the hypothesis that PGC-1alpha is
involved in the regulation of hepatic UPR and autophagy in response to both
exercise and fasting in mice. Liver-specific PGC-1alpha knockout (LKO) mice and
their floxed littermates (lox/lox) were used in two experimental parts. Liver and
plasma were obtained from (1) fed and 18 h fasted mice and (2) immediately after,
2, 6, and 10 h after 1-h treadmill running as well as from resting mice, where
one resting group was euthanized at time points corresponding to 0 and 2 h and
another corresponding to 6 and 10 h of recovery. Hepatic eIF2alpha
phosphorylation and sXBP1 mRNA content increased immediately after exercise and
IRE1alpha phosphorylation as well as cleaved ATF6 protein content was higher 2 h
into recovery than at rest in both genotypes. Fasting reduced hepatic IRE1alpha
phosphorylation and protein content as well as PERK protein and sXBP1 mRNA
content similarly in lox/lox and LKO mice. In addition, the hepatic LC3II/LC3I
protein ratio increased immediately after exercise and with fasting in both
genotypes, while fasting decreased p62 protein content in lox/lox mice. Liver
specific PGC-1alpha knockout did not affect these responses, but the LC3II/LC3I
protein ratio was higher in LKO than lox/lox mice in both rest groups. In
conclusion, the present study provides evidence for pathway-specific exercise
induced activation and fasting-induced downregulation of the UPR as well as
exercise and fasting-induced regulation of autophagy in mouse liver. In addition,
overall PGC-1alpha does not seem to be required for the fasting and exercise
induced regulation of UPR and autophagy, but may be involved in regulating basal
hepatic autophagy.
PMID- 29961150
TI - Voltammetric immunoassay for alpha-fetoprotein by using a gold
nanoparticle/dendrimer conjugate and a ferrocene derived ionic liquid.
AB - An immunosensor is described for the voltammetric determination of alpha
fetoprotein. It is making use of an AuNP-dendrimer conjugate and an ionic liquid.
A gold electrode was first modified with chitosan. Then, the AuNP-dendrimer
conjugate was covalently immobilized on the electrode. Following this, an ionic
liquid was placed on the electrode via formation of a covalent bond between the
amino groups of PAMAM and the aldehyde groups of an ionic liquid containing
ferrocene. Thus, the redox probe ferrocene becomes immobilized on the electrode
surface. PAMAM increases the amount of ferrocene immobilized on the electrode due
to its globular shape and rich amino groups. The use of AuNPs improves the
conductivity of the electrode. The modified electrode was applied to the
determination of alpha-fetoprotein in human serum and has a linear response that
covers the 0.05 to 30 ng mL-1 alpha-fetoprotein concentration range, with a
detection limit of 0.02 ng mL-1. This assay is stable, selective and
reproducible. It is perceived to provide a powerful tool for the early detection
of cancer markers. Graphical abstract Schematic of a voltammetric immunoassay for
alpha-fetoprotein based on a gold nanoparticle/dendrimer conjugate and ionic
liquids anchored with both aldehyde and ferrocene. Chit: chitosan; GA:
glutaraldehyde ; PAMAM: G4 polyamidoaminic dendrimers; AuNP: Au nanoparticle; Fc:
ferrocene; IL: ionic liquid. PB: phosphate buffer solution.
PMID- 29961152
TI - Impact of homocysteine on vasculogenic factors and bone formation in chicken
embryos.
AB - Developmental endochondral ossification requires constant blood supply, which is
provided by the embryonic vascular network. High levels of homocysteine (Hcy)
have vasculotoxic properties, but it remains unclear how Hcy disrupts blood
vessel formation in endochondral ossification. Thus, we investigated the toxicity
of Hcy on contents of vasculogenic factors (VEGF, VCAM-1, NOS3) and osteocalcin,
using developing limbs as model. Chicken embryos were submitted to treatment with
20 MUmol D-L Hcy at 12H&H and the analyses occur at 29H&H and 36H&H. We did not
identify differences in the area of limb ossification in Hcy-treated (7.5 * 105
MUm2 +/- 3.9 * 104) and untreated embryos (7.6 * 105 MUm2 +/- 3.3 * 104) at
36H&H. In Hcy-treated embryos, we observed a significantly decrease of 46.8% at
29H&H and 26.0% at 36H&H in the number of VEGF-reactive cells. Also, treated
embryos showed decrease of 98.7% in VCAM-1-reactive cells at 29H&H and 34.6% at
36H&H. The number of NOS3-reactive cells was reduced 54.0% at 29H&H and 91.5% at
36H&H, in the limbs of Hcy-treated embryos. Finally, in Hcy-treated embryos at
36H&H, we observed a reduction of 58.86% in the number of osteocalcin-reactive
cells. Here, we demonstrated for the first time that the toxicity of Hcy is
associated with a reduction in the contents of proteins involved in blood vessel
formation and bone mineralization, which interferes with endochondral
ossification of the limb during embryonic development. Graphical abstract.
PMID- 29961151
TI - Mast cells participate in allograft rejection: can IL-37 play an inhibitory role?
AB - OBJECTIVE: The aim of this study was to evaluate the role of mast cells (MCs) in
allograft rejection, eventually inhibited by IL-37. Immune cells including MCs
participate in allograft rejection by generating IL-1, IL-33, TNF and other
cytokines. METHODS: We evaluated allograft rejection on the experience of our
experimental data and using the relevant literature. RESULTS: MCs are involved in
initiation and regulation of innate and adaptive immune responses-pathways. MCs
are important pro-inflammatory cells which express high-affinity receptor FceRI
and can be activated by IgE and some pro-inflammatory cytokines, such as IL-1 and
IL-33. The cross-linkage of high affinity IgE receptor on MCs by antigen ligation
has a crucial role in allergy, asthma, anaphylaxis, cancer and allograft
rejection. MCs mediate immunity in organ transplant, leading to the activation of
allospecific T cells implicated in the rejection and generate pro-inflammatory
cytokines/chemokines. IL-1 pro-inflammatory cytokine family members released by
MCs mediate allograft rejection and inflammation. IL-37 is also an IL-1 family
member generated by macrophage cell line in small amounts, which binds to IL
18Ralpha and produces an anti-inflammatory effect. IL-37 provokes the inhibition
of TLR signaling, TLR-induced mTOR and (MyD88)-mediated responses, suppressing
pro-inflammatory IL-1 family members and increasing IL-10. CONCLUSION: IL-37
inhibition offers the opportunity to immunologically modulate MCs, by suppressing
their production of IL-1 family members and reducing the risk of allograft
rejection, resulting as a potential good therapeutic new cytokine. Here, we
report the relationship between inflammatory MCs, allograft rejection and pro
inflammatory and anti-inflammatory IL-37.
PMID- 29961154
TI - Brachial plexus injury after shoulder dislocation: a literature review.
AB - Brachial plexus injuries are among the rarest but at the same time the most
severe complications of shoulder dislocation. The symptoms range from transient
weakening or tingling sensation of the upper limb to total permanent paralysis of
the limb associated with chronic pain and disability. Conflicting opinions exist
as to whether these injuries should be treated operatively and if so when surgery
should be performed. In this review, available literature dedicated to
neurological complications of shoulder dislocation has been analysed and
management algorithm has been proposed. Neurological complications were found in
5.4-55% of all dislocations, with the two most commonly affected patient groups
being elderly women sustaining dislocation as a result of a simple fall and young
men after high-energy injuries, often multitrauma victims. Infraclavicular part
of the brachial plexus was most often affected. Neurapraxia or axonotmesis
predominated, and complete nerve disruption was observed in less than 3% of the
patients. Shoulder dislocation caused injury to multiple nerves more often than
mononeuropathies. The axillary nerve was most commonly affected, both as a single
nerve and in combination with other nerves. Older patient age, higher energy of
the initial trauma and longer period from dislocation to its reduction have been
postulated as risk factors. Brachial plexus injury resolved spontaneously in the
majority of the patients. Operative treatment was required in 13-18% of the
patients in different studies. Patients with suspected neurological complications
require systematic control. Surgery should be performed within 3-6 months from
the injury when no signs of recovery are present.
PMID- 29961153
TI - Revisiting the Children-of-Twins Design: Improving Existing Models for the
Exploration of Intergenerational Associations.
AB - Datasets comprising twins and their children can be a useful tool for
understanding the nature of intergenerational associations between parent and
offspring phenotypes. In the present article we explore structural equation
models previously used to analyse Children-of-Twins data, highlighting some
limitations and considerations. We then present new variants of these models,
showing that extending the models to include multiple offspring per parent
addresses several of the limitations discussed. Accompanying the updated models,
we provide power calculations and demonstrate with application to simulated data.
We then apply to intergenerational analyses of height and weight, using a sub
study of the Norwegian Mother and Child Cohort (MoBa); the Intergenerational
Transmission of Risk (IToR) project, wherein all kinships in the MoBa data have
been identified (a children-of-twins-and-siblings study). Finally, we consider
how to interpret the findings of these models and discuss future directions.
PMID- 29961155
TI - Calcium-sensing receptor (CaSR) modulates vacuolar H+-ATPase activity in a cell
model of proximal tubule.
AB - BACKGROUND: The calcium-sensing receptor (CaSR) is localized in the apical
membrane of proximal tubules in close proximity to the transporters responsible
for proton secretion. Therefore, the aim of the present study was to analyze the
effects of CaSR stimulation on the biochemical activity of the vacuolar H+-ATPase
in a cellular model of proximal tubule cells, OKP cells. METHODS: Biochemical
activity of H+-ATPase was performed using cell homogenates, and the inorganic
phosphate released was determined by a colorimetric method. Changes in cytosolic
ionized calcium [Ca2+]i were also determined using Fluo-4. RESULTS: A significant
increase of vacuolar H+-ATPase activity was observed when the CaSR was stimulated
with agonists such as Gd3+ (300 uM) and neomycin (200 uM). This activity was also
stimulated in a dose-dependent fashion by changes in extracellular Ca2+ (Ca2+o)
between 10-4 and 2 mM. Gd3+ and neomycin produced a sustained rise of [Ca2+]i, an
effect that disappears when extracellular calcium was removed in the presence of
0.1 uM thapsigargin. Inhibition of phospholipase C (PLC) activity with U73122 (5
* 10-8 M) reduced the increase in [Ca2+]i induced by neomycin. CONCLUSION: CaSR
stimulation induces an increase in the vacuolar H+-ATPase activity of OKP cells,
an effect that involves an increase in [Ca2+]i and require phospholipase C
activity. The consequent decrease in intratubular pH could lead to increase
ionization of luminal calcium, potentially enhancing its reabsorption in distal
tubule segments and reducing the formation of calcium phosphate stones.
PMID- 29961156
TI - Characterising skeletal muscle haemoglobin saturation during exercise using near
infrared spectroscopy in chronic kidney disease.
AB - BACKGROUND: Chronic kidney disease (CKD) patients have reduced exercise capacity.
Possible contributing factors may include impaired muscle O2 utilisation through
reduced mitochondria number and/or function slowing the restoration of muscle ATP
concentrations via oxidative phosphorylation. Using near-infrared spectroscopy
(NIRS), we explored changes in skeletal muscle haemoglobin/myoglobin O2
saturation (SMO2%) during exercise. METHODS: 24 CKD patients [58.3 (+/- 16.5)
years, eGFR 56.4 (+/- 22.3) ml/min/1.73 m2] completed the incremental shuttle
walk test (ISWT) as a marker of exercise capacity. Using NIRS, SMO2% was measured
continuously before, during, and after (recovery) exercise. Exploratory
differences were investigated between exercise capacity tertiles in CKD, and
compared with six healthy controls. RESULTS: We identified two discrete phases; a
decline in SMO2% during incremental exercise, followed by rapid increase upon
cessation (recovery). Compared to patients with low exercise capacity [distance
walked during ISWT, 269.0 (+/- 35.9) m], patients with a higher exercise capacity
[727.1 (+/- 38.1) m] took 45% longer to reach their minimum SMO2% (P = .038) and
recovered (half-time recovery) 79% faster (P = .046). Compared to controls, CKD
patients took significantly 56% longer to recover (i.e., restore SMO2% to
baseline, full recovery) (P = .014). CONCLUSIONS: Using NIRS, we have determined
for the first time in CKD, that favourable SMO2% kinetics (slower deoxygenation
rate, quicker recovery) are associated with greater exercise capacity. These
dysfunctional kinetics may indicate reduced mitochondria capacity to perform
oxidative phosphorylation-a process essential for carrying out even simple
activities of daily living. Accordingly, NIRS may provide a simple, low cost, and
non-invasive means to evaluate muscle O2 kinetics in CKD.
PMID- 29961158
TI - Response to Costa, Lemos, and Paneque Letter to the Editor.
PMID- 29961157
TI - Trans-spliced long non-coding RNA: an emerging regulator of pluripotency.
AB - With dual capacities for unlimited self-renewal and pluripotent differentiation,
pluripotent stem cells (PSCs) give rise to many cell types in our body and PSC
culture systems provide an unparalleled opportunity to study early human
development and disease. Accumulating evidence indicates that the molecular
mechanisms underlying pluripotency maintenance in PSCs involve many factors.
Among these regulators, recent studies have shown that long non-coding RNAs
(lncRNAs) can affect the pluripotency circuitry by cooperating with master
pluripotency-associated factors. Additionally, trans-spliced RNAs, which are
generated by combining two or more pre-mRNA transcripts to produce a chimeric
RNA, have been identified as regulators of various biological processes,
including human pluripotency. In this review, we summarize and discuss current
knowledge about the roles of lncRNAs, including trans-spliced lncRNAs, in
controlling pluripotency.
PMID- 29961159
TI - Toxicity and uptake of nanoparticulate and bulk ZnO in nematodes with different
life strategies.
AB - Despite the increasing number and quantity of nanomaterials released in the
environment, our knowledge on their bioavailability and possible toxicity to
organisms is rather limited. Thus, we know quite little about sensitivity of
various nematode feeding types and life strategies to treatments with nano metal
oxides. The toxicity of zinc oxide nanoparticles (nano-ZnO) (with a particle size
of 25 nm) and the bulk counterpart was investigated in two free-living nematode
species of different life strategies: Xiphinema vuittenezi, a K-strategist plant
feeder nematode and Panagrellus redivivus, an r-strategist bacterivor nematode.
The internal zinc concentration and the concentration of minor and trace elements
were determined by total reflection X-ray fluorescence spectrometry.
Concentration-dependent mortality in both nematode species was observed following
a 24-h exposure both to nano-ZnO and bulk ZnO. The zinc concentration of the
treating suspension had a significant effect on the internal zinc content of the
animals in both cases. Particle size did not influence the internal zinc content.
Our results show that nano and bulk ZnO have a similar dose-response effect on
mortality of the bacterivor P. redivivus. In contrast, the nano-ZnO has stronger
toxic effect on the mortality of X. vuittenezi. In general, X. vuittenezi did not
react more sensitively to the treatments than P. redivivus, but appeared
sensitive to the nano-ZnO treatment compared to bulk ZnO.
PMID- 29961160
TI - BMPLS: Blockchain-Based Multi-level Privacy-Preserving Location Sharing Scheme
for Telecare Medical Information Systems.
AB - The sharing of patients' locations is an important part in mobile medical
services and modern smart healthcare. Although location sharing based on
blockchains has advantages on decentralization and openness, there is also a
challenge to guarantee the security and the privacy of locations recorded in a
blockchain. To this end, this paper investigates the location sharing based on
blockchains for telecare medical information systems. Firstly, we define the
basic requirements of blockchain-based location sharing including
decentralization, unforgeability, confidentiality, multi-level privacy
protection, retrievability and verifiability. Then, using order-preserving
encryption and merkle tree, we propose a blockchain-based multi-level location
sharing scheme, i.e. BMPLS. The analysis results show that our scheme satisfies
the above requirements. Finally, the performance of our scheme is evaluated and
the experiment results show that our scheme is efficient and feasible for both
patients and medical workers. In a word, our scheme can be applied to realize
privacy-preserving location sharing based on blockchains for telecare medical
information systems.
PMID- 29961161
TI - Joint longitudinal model development: application to exposure-response modeling
of ACR and DAS scores in rheumatoid arthritis patients treated with sirukumab.
AB - Exposure-response modeling is important to optimize dose and dosing regimen in
clinical drug development. The joint modeling of multiple endpoints is made
possible in part by recent progress in latent variable indirect response (IDR)
modeling for ordered categorical endpoints. This manuscript presents the results
of joint modeling of continuous and ordered categorical endpoints in the latent
variable IDR modeling framework through the sharing of model parameters, with an
application to the exposure-response modeling of sirukumab. Sirukumab is a human
anti- interleukin-6 (IL-6) monoclonal antibody that binds soluble human IL-6 thus
blocking IL-6 signaling, which plays a major role in the pathophysiology of
rheumatoid arthritis (RA). A phase 2 clinical trial was conducted in patients
with active RA despite methotrexate therapy, who received subcutaneous (SC)
administration of either placebo or sirukumab of 25, 50 or 100 mg every 4 weeks
(q4w) or 100 mg every 2 weeks (q2w). Major efficacy endpoints were the 20, 50,
and 70% improvement in the American College of Rheumatology (ACR20, ACR50, and
ACR70) disease severity criteria, and the 28-joint disease activity score using C
reactive protein (DAS28). The ACR endpoints were treated as ordered categorical
and DAS28 as continuous. The results showed that, compared with the common
approach of separately modeling the endpoints, the joint model could describe the
observed data better with fewer parameters through the sharing of random effects,
and thus more precisely characterize the dose-response relationship. The
implications on future dose and dosing regimen optimization are discussed in
contrast with those from landmark analysis.
PMID- 29961162
TI - Comparative Analysis of Regulatory Role of Notch Signaling Pathway in 8 Types
Liver Cell During Liver Regeneration.
AB - Notch signaling is closely related to cell proliferation, cell apoptosis, cell
fate decisions, DNA damage repair, and so on. However, the exactly regulatory
mechanism of Notch signaling pathway in liver regeneration (LR) remains unclear.
To reveal the role of Notch signaling pathway in rat liver regeneration,
Ingenuity Pathway Analysis (IPA) software and related pathway database were
firstly used to construct the Notch signaling pathway in this study. Next, eight
type cells with high purity were obtained by Percoll density centrifugation and
immunomagnetic beads sorting. Then, the expression profiles of Notch signaling
pathway-related genes in eight type cells were checked by using Rat Genome 230
2.0 Array, and the results showed that the expression of 42 genes were
significantly regulated. H-cluster results showed that the hepatic stellate cells
are attributed to one cluster; hepatocyte cell, oval cell, sinusoidal endothelial
cell, and Kupffer cell are clustered together; and biliary epithelial cell, pit
cell, and dendritic cell are one cluster. IPA software and Expression analysis
systematic explorer analysis indicated that Notch signaling pathway-related genes
were involved in cell proliferation, apoptosis, cell cycle, DNA damage repair,
etc. In conclusion, Notch signaling pathway might regulate various physiological
activities of LR through multiple pathways.
PMID- 29961163
TI - Oral Health Challenges in Refugees from the Middle East and Africa: A Comparative
Study.
AB - The aim was to explore and compare oral health and need for dental treatment in
newly arrived refugees from the Middle East and Africa to Norway. Oral
examination and structured interviews were performed with attending interpreters.
Associations between origin and measures for oral health were studied with
multiple linear regression. Half of the refugees (n = 132) reported oral impacts
on daily performances (OIDP) and mean number of decayed teeth (DT) was 4.3 (SD
3.5). Refugees from the Middle East had more DT (1.38, p = 0.044), higher sum of
decayed, missing and filled teeth (DMFT) (3.93, p = 0.001) and lower OIDP-score (
3.72, p = 0.026) than refugees from Africa. Refugee oral health is generally
poor, with more extensive challenges in refugees from the Middle East. However,
few missing teeth, and manageable caries-gradient at the time of registration
indicate that most refugees have the prerequisites for a good dentition, provided
they get the necessary treatment.
PMID- 29961164
TI - Cumulative Stress and Trauma from the Migration Process as Barriers to HIV
Testing: A Qualitative Study of Latino Immigrants.
AB - Immigrants are at increased risk for late HIV testing; however, there is limited
understanding of how migration to the United States shapes HIV testing behaviors.
This study examined the relationship between the migration process and HIV
testing among Latino immigrants. Semi-structured, in-depth interviews were
conducted in March and April 2017 with 34 Latino immigrants in New York City.
Grounded theory guided analysis of the qualitative data. Results indicated that
Latino immigrants experienced cumulative stress and trauma throughout the
migration process that contributed to significant emotional and psychological
consequences. Stress and trauma accumulated from the migration process posed
barriers to HIV testing as Latino immigrants sought to avoid activities perceived
as stressful, including learning one's HIV status. Targeted interventions that
ameliorate the stressful effects of migration may facilitate preventive health
behaviors among Latino immigrants.
PMID- 29961165
TI - Benzylpenicillin versus wide-spectrum beta-lactam antibiotics as empirical
treatment of Haemophilus influenzae-associated lower respiratory tract infections
in adults; a retrospective propensity score-matched study.
AB - There is consensus that definitive therapy for infections with H. influenzae
should include antimicrobial agents with clinical breakpoints against the
bacterium. In Scandinavia, benzylpenicillin is the recommended empirical
treatment for community-acquired pneumonia (CAP) except in very severe cases.
However, the effect of benzylpenicillin on H. influenzae infections has been
debated. The aim of this study was to compare the outcomes of patients given
benzylpenicillin with patients given wide-spectrum beta-lactams (WSBL) as
empirical treatment of lower respiratory tract H. influenzae infections requiring
hospital care. We identified 481 adults hospitalized with lower respiratory tract
infection by H. influenzae, bacteremic and non-bacteremic. Overall, 30-day
mortality was 9% (42/481). Thirty-day mortality, 30-day readmission rates, and
early clinical response rates were compared in patients receiving
benzylpenicillin (n = 199) and a WSBL (n = 213) as empirical monotherapy. After
adjusting for potential confounders, empirical benzylpenicillin treatment was not
associated with higher 30-day mortality neither in a multivariate logistic
regression (aOR 2.03 for WSBL compared to benzylpenicillin, 95% CI 0.91-4.50, p =
0.082), nor in a propensity score-matched analysis (aOR 2.14, 95% CI 0.93-4.92, p
= 0.075). Readmission rates did not significantly differ between the study
groups, but early clinical response rates were significantly higher in the WSBL
group (aOR 2.28, 95% CI 1.21-4.31, p = 0.011), albeit still high in both groups
(84 vs 81%). In conclusion, despite early clinical response rates being slightly
lower for benzylpenicillin compared to WSBL, we found no support for increased
mortality or readmission rates in patients empirically treated with
benzylpenicillin for lower respiratory tract infections by H. influenzae.
PMID- 29961166
TI - How small modifications in laboratory workflow of blood cultures can have a
significant impact on time to results.
AB - Rapid identification and antimicrobial susceptibility testing of micro-organisms
causing bloodstream infections is crucial in the management of septic patients.
In this study, we compared a period of twice-daily and a period of thrice-daily
reading of subculture agar plates. In 2016, 10,644 positive blood cultures
bottles (bioMerieux) from 2608 patients were analyzed at UZ Leuven.
Identification and antimicrobial susceptibility testing were performed by MALDI
TOF MS (Bruker Daltonics) and Vitek 2 (bioMerieux) respectively. In period 1
(January to June), subculture plates were read at 8:30 a.m. and 2:00 p.m. during
the weekdays. In period 2 (August until December), reading was performed at 8:30
a.m., 2:00 p.m., and 5:00 p.m. Time to identification and time to AST results
after positivity were compared. In period 1, median time to identification of all
organisms was 22.8 h compared to 20.2 h in period 2 (p < 0.01). Moreover, micro
organisms were identified before 12 h in 9% of samples in period 2, a significant
increase compared to 2% in period 1 (p < 0.01). In period 2, AST results were
known within 36 h in 39% of samples, compared to 31% in period 1 (p < 0.01).
Optimization of the reading frequency of subcultures of blood cultures
significantly decreases time to results. Further optimization can be done by
introducing lab automation. We will use the data of this study as a baseline to
analyze the impact of introducing WASPLab (Copan Diagnostics) automation on time
to results.
PMID- 29961167
TI - Identifying Psychosocial Problems Among Children and Youth in the Child Welfare
System Using the PSC-17: Exploring Convergent and Discriminant Validity with
Multiple Informants.
AB - Youth who enter foster care are at risk of mental health need, but questions
arise as to the validity of their self-reported symptomatology. This study
examines the screening validity of the youth-report version of the Pediatric
Symptom Checklist-17 (PSC-17) in a child welfare population. Data come from 2389
youth who completed a version of the PSC-17 adapted for youth report, and their
biological and foster parents who completed the parent-report version. Youth also
completed a shortened version of the Screen for Child Anxiety Related Disorders
(SCARED). Convergent and discriminant validity of the PSC-17 was assessed using
multi-trait multi-method matrices. The PSC-17's internalizing subscale was
strongly correlated, attention subscale was moderately correlated, and
externalizing subscale was weakly correlated with the SCARED's anxiety and PTSD
subscales. Comparing youth and foster parent scores, the PSC-17 had moderate
convergent validity and weak/fair discriminant validity. Comparing youth, foster
parent, and biological parent scores, the PSC-17 had moderate convergent validity
and weak/fair discriminant validity. The current study provides some support for
the validity of the PSC-17 for the population of youth in foster care.
PMID- 29961168
TI - Quality of social interaction in foster dyads at child age 2 and 3 years.
AB - The main aim of this study was to investigate the quality of social interaction
between 60 foster parents and their foster children compared to a group of 55 non
foster families at 2 (T1) and again at 3 (T2) years of age. Video observations
were used to investigate child-parent interaction at both time-points. "This is
My Baby" interview was administered to investigate foster parents' commitment at
T1. The main results revealed significant group differences at T1 on all child
parent social interaction measures, although not at T2. Further, a significant
group by time interaction was identified for parental sensitivity, revealing a
positive development over time in the foster group. Finally, a significant
positive relation was found between commitment at T1 and parental sensitivity.
The results convey an optimistic view of the possibilities for foster dyads to
develop positive patterns of social interaction over time.
PMID- 29961169
TI - Choice of a spin singlet or triplet: electronic properties of Bis-Co(II), Bis
Ni(II), Bis-Cu(II) and Bis-Zn(II) oxygen doubly N-confused hexaphyrin
(1.1.1.1.1.1).
AB - Fused hexaphyrins have many physical and chemical properties and can coordinate
transition metal ions. In this study, we investigated the geometric structure,
charge decomposition analysis (CDA), spin density, frontier molecular orbital
(FMO) compositions and absorption spectra of four oxygen doubly N-confused
hexaphyrin (1.1.1.1.1.1) (ONCP) complexes with the metal ions Co(II), Ni(II),
Cu(II) and Zn(II) (designated ONCP-d-Co, ONCP-d-Ni, ONCP-d-Cu and ONCP-d-Zn).
Based on their energies, geometric structures, FMO characteristics and comparison
to experiments, ONCP-d-Co and ONCP-d-Cu have the mix-states of the triplet state
and broken-symmetry state (antiferromagnetic state) rather than the spin singlet
of a closed shell as previously reported. Moreover, based on analyses of the spin
density and spin population of the spin triplet ONCP-d-Co and ONCP-d-Cu
complexes, the charge transfer in ONCP-d-Cu is greater than that in ONCP-d-Co
because the spin density in ONCP-d-Cu is concentrated not only on the Cu ion but
also on the ONCP ligand. Thus, the CDA value for ONCP-d-Cu is larger. Finally,
through comparative analysis of the FMO compositions and absorption spectra, the
complexes and ligand are shown to have very similar absorption spectra with
characteristics that arise mainly from pi -> pi* transitions both in the B-band
and the Q-band, which is due to the FMO compositions being dominated by the
highly delocalized conjugated system, rather than by the metal ions. The
absorption maxima of the Q-band are ONCP-d-Co (1020 nm) > ONCP-d-Zn (1012 nm) >
ONCP-d-Ni (997 nm) > ONCP-d-Cu (988 nm), which is inversely proportional to the
energy gap in their FMOs. Graphical Abstract The present work investigates the
geometric structure, charge decomposition analysis (CDA), spin density, frontier
molecular orbital (FMO) compositions and absorption spectra of four oxygen doubly
N-confused hexaphyrin (1.1.1.1.1.1) (ONCP) complexes with the metal ions Co(II),
Ni(II), Cu(II) and Zn(II) (designated ONCP-d-Co, ONCP-d-Ni, ONCP-d-Cu and ONCP-d
Zn). Based on their energies, geometric structures, FMO characteristics and
comparison to experiments, ONCP-d-Co and ONCP-d-Cu have the mix-state of the
triplet state and broken-symmetry state (antiferromagnetic state) rather than the
spin singlet of a close shell as were previously reported. Meanwhile, ONCP-d-Ni
and ONCP-d-Zn show spin singlet structure. The calculated CDA shows the following
order: ONCP-d-Cu (1.487) > ONCP-d-Ni (1.255) > ONCP-d-Co (1.211) > ONCP-d-Zn
(1.201). Through comparisons of spin density and spin populations of ONCP-d-Co
and ONCP-d-Cu, charge transfer between Cu and ligand ONCP is greater than that of
Co and ONCP, which makes the CDA value of ONCP-d-Cu obviously larger than that of
the other complexes.
PMID- 29961170
TI - Evolutionary dynamics of transposable elements during silkworm domestication.
AB - Although there are some documented examples on population dynamics of
transposable elements (TEs) in model organisms, the evolutionary dynamics of TEs
in domesticated species has not been systematically investigated. The objective
of this study is to understand population dynamics of TEs during silkworm
domestication. In this work, using transposon-display we examined the
polymorphism of seven TE families [they represent about 59% of silkworm (Bombyx
mori) total TE content] in four domesticated silkworm populations and one wild
silkworm population. Maximum likelihood (ML) was used to estimate selection
pressure. Population differentiation and structure were performed by using AMOVA
analysis and program DISTRUCT, respectively. The results of transposon-display
showed that significant differentiation occurred between the domesticated
silkworm and wild silkworm. These TEs have experienced expansions and fixation in
the domesticated silkworm but not in wild silkworm. Furthermore, the ML results
indicated that purifying selection of TEs in the domesticated silkworm were
significantly weaker than that in the wild silkworm. Interestingly, an adaptation
insertion induced by BmMITE-2 was found, and this insertion can reduce the
polymorphism of the flanking regions of its neighboring COQ7 gene. Our results
suggested that TEs expanded and were fixed in the domesticated silkworm might
result from demographic effects and artificial selection during domestication. We
concluded that the data presented in this study have general implication in
animal and crop improvements as well as in domestication of new species.
PMID- 29961172
TI - The validity of the surgical indication for intraductal papillary mucinous
neoplasm of the pancreas advocated by the 2017 revised International Association
of Pancreatology consensus guidelines.
AB - PURPOSE: This study was performed to evaluate the surgical indication for
intraductal papillary mucinous neoplasm (IPMN) advocated by the 2017 revised
International Association of Pancreatology consensus guidelines (IAPCG2017).
METHODS: The medical records of 63 patients who underwent pancreatectomy for IPMN
were retrospectively reviewed. RESULTS: Thirteen patients had main-duct IPMN, 25
had mixed IPMN, and 25 had branch-duct IPMN with frequencies of high-grade
dysplasia or invasive carcinoma of 62, 24, and 28%, respectively. The sensitivity
and specificity of high-risk stigmata for high-grade dysplasia or invasive
carcinoma advocated by the IAPCG2017 were 90 and 67%, respectively. Of 17
patients with invasive carcinoma, all patients had high-risk stigmata, and 16 had
an enhanced mural nodule (MN) of >= 5 mm. The sensitivity and specificity of a >=
5-mm enhanced MN for predicting invasive carcinoma were 94% and 87%,
respectively. CONCLUSIONS: Introducing a size threshold for enhanced MNs into the
assessment of high-risk stigmata increases the specificity without jeopardizing
the sensitivity. The surgical indication for any type of IPMN may be determined
using only a >= 5-mm enhanced MN. When the type of IPMN is classified strictly,
about half of IPMNs are mixed type, and most are benign. The surgical indication
for mixed IPMN should be reconsidered.
PMID- 29961171
TI - Curcumin Attenuates Airway Inflammation and Airway Remolding by Inhibiting NF
kappaB Signaling and COX-2 in Cigarette Smoke-Induced COPD Mice.
AB - The purpose of this study is to evaluate the therapeutic effects of curcumin on
airway inflammation using LPS and cigarette smoke (LC)-induced COPD murine models
and LPS-stimulated human bronchial epithelial (BEAS-2B) cells. In this research,
COPD murine models were established after challenged with LPS for 2 days and
exposed to cigarette smoke for 35 days. Treatment with curcumin for 10 days
distinctly alleviated airway inflammation and airway remolding in LC-induced COPD
mice according to the lung H&E histopathological examination. The number of
neutrophils and lymphocytes in broncho alveolar lavage fluid (BALF) was
significantly decreased in curcumin+LC-treated group compared with the LC-induced
mice. Additionally, curcumin inhibited BEAS-2B cells proliferation, which
suggested the preventive effect of curcumin on progressive airway remolding and
inflammatory response mediated by bronchial epithelial cells. Further
investigation demonstrated an underlying molecular mechanism for the therapeutic
effects of curcumin may rely on the inhibition of the degradation of IkappaBalpha
and COX-2 expression in curcumin+LC-treated COPD mice and LPS-stimulated BEAS-2B
cells. Overall, curcumin alleviates the airway inflammation and airway remolding,
which is closely related to inhibit the BEAS-2B cells proliferation and suppress
the activation of NF-kappaB and COX-2 expression. These findings indicate that
curcumin may be a potential agent for the therapy of COPD.
PMID- 29961173
TI - Magnetic resonance-based pelvimetry and tumor volumetry can predict surgical
difficulty and oncologic outcome in locally advanced mid-low rectal cancer.
AB - PURPOSE: To investigate the impact of the pelvic dimensions and tumor volume on
surgery in locally advanced rectal cancer. METHODS: Patients who underwent open
surgery after neoadjuvant long-course chemoradiation for primary rectal cancer
were included. The predictive value of magnetic resonance-based pelvic
measurements and tumor volume on the surgical difficulty and oncologic outcome
were analyzed. RESULTS: 125 patients were included. The independent risk factors
related to the circumferential resection margin status were the pT stage [odds
ratio (OR) 3.64, confidence interval (CI) 1.409-7.327] and tumor volume after
neoadjuvant chemoradiotherapy (OR 1.59, CI 1.018-2.767). The operative time (p =
0.014, OR 1.453) and pelvic depth (p = 0.023, OR 1.116) were independent
predictive factors for anastomotic leak. The median follow-up was 72 (2-113)
months. Local recurrence was seen in 17 (14.1%) patients. Anastomotic leak (OR
1.799, CI 0.978-3.277), the circumferential resection margin status (OR 3.217, CI
1.262-7.870) and the relative tumor volume rate (OR 1.260, CI 1.004-1.912) were
independent prognosticators of local recurrence. The 5-year overall survival was
66.7%. The circumferential resection margin status (hazard ratio: 4.739, CI 2.276
9.317), pN stage (OR 3.267, CI 1.195-8.930) and relative tumor volume rate (OR
2.628, CI 1.042-6.631) were independent prognostic factors for the overall
survival. CONCLUSIONS: Relative dimensions of the tumor in the pelvis influence
the local recurrence and overall survival rates. Magnetic resonance-based
measurements can predict the difficulty of surgery and allow surgeons to consider
the appropriate surgical approach.
PMID- 29961174
TI - Molecular analysis of an asbestos-exposed Belgian family with a high prevalence
of mesothelioma.
AB - Familial clustering of malignant mesothelioma (MM) has been linked to the
presence of germline mutations in BAP1. However, families with multiple MM
patients, without segregating BAP1 mutation were described, suggesting the
existence of other predisposing genetic factors. In this study, we report a
previously undescribed Belgian family, in which BAP1 was found to be absent in
the epithelial malignant mesothelial cells of the index patient. Whole exome
analysis did not reveal a germline or somatic BAP1 variant. Also, no germline or
somatic copy number changes in the BAP1 region could be identified. However,
germline variants, predicted to be damaging, were detected in 11 other 'Cancer
census genes' (i.e. MPL, RBM15, TET2, FAT1, HLA-A, EGFR, KMT2C, BRD3, NOTCH1, RB1
and MYO5A). Of these, the one in RBM15 seems to be the most interesting given its
low minor allele frequency and absence in the germline DNA of the index patient's
mother. The importance of this 'Cancer census gene' in familial MM clustering
needs to be evaluated further. Nevertheless, this study strengthens the suspicion
that, next to germline BAP1 alterations, other genetic factors might predispose
families to the development of MM.
PMID- 29961175
TI - Clinicopathological value of programmed cell death 1 (PD-1) and programmed cell
death ligand 1 (PD-L1) expression in synovium of patients with rheumatoid
arthritis.
AB - The etiology of rheumatoid arthritis (RA) is thought to involve dysfunction of
the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway;
PD-1 negatively regulates autoimmunity by interacting with its ligand, PD-L1. We
therefore investigated PD-1/PD-L1 expression in synovial tissue of patients with
RA. We immunohistochemically stained synovial specimens from 51 patients with RA
and assessed the association between PD-1/PD-L1 expression and rheumatoid factor
(RF), the total count of infiltrating T cells, C-reactive protein (CRP), and
Krenn's synovitis score. PD-1 expression on infiltrating lymphocytes was detected
in 34/51 RA cases (66.7%), while PD-1 expression was very mildly correlated only
with the number of total infiltrating T cells (R2 = 0.1011, P = 0.0230). On the
other hand, PD-L1 expression on synovial lining cells was observed in 37/51 RA
cases (72.5%). Furthermore, a higher PD-L1 expression was significantly
associated with RF positive state (P = 0.0454), and the correlations between PD
L1 expression and the number of infiltrating T cells (R2 = 0.5571, P < 0.0001),
CRP (R2 = 0.4060, P < 0.0001), and Krenn's synovitis score (R2 = 0.7785, P <
0.0001) were confirmed. PD-1 was expressed on infiltrating lymphocytes, while PD
L1 was expressed on synovial lining cells; the expression of PD-L1 on synovial
lining cells was significantly correlated with the active state of the disease.
These data suggest that PD-1/PD-L1 pathway may have an important role in the
pathogenesis of RA.
PMID- 29961176
TI - First report of the isolation of Balamuthia mandrillaris in the northern region
of Japan.
AB - Balamuthia mandrillaris is a free-living amoeba that lives in soil and water near
human settlements. B. mandrillaris was first isolated from a mandrill baboon that
died at the San Diego Zoo Wildlife Park in California in 1986, and the first
human infection was reported in 1990. Although reported B. mandrillaris
infections are often not properly characterized, it appears that B. mandrillaris
invades the living body from the soil and water, either via a wound or the nasal
cavity. Most confirmed infections have originated in South and North America. B.
mandrillaris inhabits warm climates and is recognized as a pathogen in warm areas
such as desert climates and tropical climates. B. mandrillaris has been isolated
from environmental samples since 2000, most of which originated from warm areas
such as step climates, tropical climates, and desert climates. However, B.
mandrillaris may survive in diverse environments, although fewer granulomatous
amebic encephalitis patients have been reported in colder Japanese and Northern
European regions. In the present study, we conducted a survey of 13 soil samples
in Aomori Prefecture located at the northernmost tip of Japan Honshu and
successfully isolated one strain of B. mandrillaris from soil for the first time
in Japan. In addition, B. mandrillaris gene was detected from several soils. This
confirms that B. mandrillaris is capable of spreading to a wider climatic region.
PMID- 29961177
TI - Reply to the letter: Evaluation of hyoscine N-butyl bromide efficacy on the
prevention of catheter-related bladder discomfort after transurethral resection
of prostate: a prospective randomized, double-blind control trial.
PMID- 29961178
TI - Ultrasound-guided peripheral intravenous access placement for children in the
emergency department.
AB - : The usefulness of ultrasound guidance in peripheral intravenous access
placement has yet to be established in children. In this prospective comparative
study, we investigated success rates of intravenous access placement with
ultrasound guidance in a pediatric emergency department. After a failed first
attempt with the conventional technique, the second and third attempts were
conducted using either the ultrasound guidance (a real-time, dual operator
method) or the conventional technique. The success rates within the two
interventional attempts were then compared. From a total of 712 participants,
those with a failed first attempt were allocated to the ultrasound guidance (n =
99) and conventional technique (n = 100) groups. The success rate was
significantly lower for the ultrasound guidance (65%) than for the conventional
technique (84%) group (p = 0.002, chi-square test). This remained significant
after adjusting for confounders with multiple logistic regression analysis (odds
ratio 2.60, 95% confidence interval 1.26-5.37, p = 0.001). CONCLUSION: Ultrasound
guided intravenous access placement using a real-time, dual operator method led
to a significantly lower success rate than the conventional technique in children
with one failed conventional attempt in the emergency department. TRIAL
REGISTRATION: UMIN000014730 What is Known: * Children experience a low success
rate (about 60% with 1 attempt and about 90% with 4 attempts) for IV access
placement. * Ultrasound guidance may lead to a decreased number of attempts and
shorter procedural time with comparable overall IV success rate. What is New: *
Ultrasound-guided IV placement (a real-time, dual operator method) actually led
to a significantly lower IV success rate than the conventional technique in
children in the emergency department. * Our result warrants further trials to
determine the precise population who benefits from ultrasound guidance.
PMID- 29961179
TI - Gastric Plication and Sleeve Gastrectomy in an Experimental Model of Obesity: New
Insights into Weight Loss, Intake and Metabolic Results.
AB - AIM: Laparoscopic gastric plication (LGP) is a bariatric surgical technique based
on the anatomical principles of laparoscopic sleeve gastrectomy (LSG), but its
effects on the metabolic profile are still uncertain. The aim of our study is to
compare the changes in weight, metabolic parameters and gastric histology
following intervention by gastric plication (GP) and sleeve gastrectomy (SG) in
an experimental model of obesity. METHODS: To conduct the study, 32 8-week-old
male Sprague-Dawley rats (Charles River(r)) were fattened by means of a cafeteria
diet and randomly assigned to the following experimental groups: group 1: GP (n =
12); group 2: SG (n = 12) and group 3: sham (n = 8). RESULTS: Unlike the SG
group, the GP group attained the weight of the sham group at the end of the
experiment (week 16). The GP group continued to eat more cafeteria diet than the
SG group. In addition, the SG group achieved better glycaemic control than the GP
group. Significantly higher plasma ghrelin levels were observed at week 16 in the
GP group than in the SG group (2.29 +/- 0.5 vs 1.07 +/- 0.4, p < 0.05), which
also occurred for the glucagon plasmatic levels (62.71 +/- 36.2 vs 24.63 +/- 9.3,
p < 0.05). CONCLUSIONS: GP is not as effective as SG and cannot be considered a
metabolic surgery due to observed hormonal variations. The animals subjected to a
GP continued to have a high appetite for the cafeteria diet unlike the animals
submitted to an SG. Hormonal mechanisms possibly related to glucagon and ghrelin
may be involved in this metabolic response.
PMID- 29961180
TI - Diet shifts by adult flightless dung beetles Circellium bacchus, revealed using
DNA metabarcoding, reflect complex life histories.
AB - Life history changes may change resource use. Such shifts are not well understood
in the dung beetles, despite recognised differences in larval and adult feeding
ability. We use the flightless dung beetle Circellium bacchus to explore such
shifts, identifying dung sources of adults using DNA metabarcoding, and comparing
these with published accounts of larval dung sources. C. bacchus is traditionally
considered to specialise on the dung of large herbivores for both larval and
adult feeding. We successfully extracted mammal DNA from 151 adult C. bacchus
fecal samples, representing 16 mammal species (ranging from elephants to small
rodents), many of which are hitherto undescribed in the diet. Adult C. bacchus
showed clear dung source preferences, especially for large herbivores inhabiting
dense-cover vegetation. Our approach also confirmed the presence of cryptic taxa
in the study area, and we propose that this may be used for biodiversity survey
and monitoring purposes. Murid rodent feces were the most commonly fed-upon dung
source (77.5%) for adult C. bacchus, differing markedly from the large and
megaherbivore dung sources used for larval rearing. These findings support the
hypothesis of life history-specific shifts in resource use in dung beetles, and
reveal a hitherto unsuspected, but ecologically important, role of these dung
beetles in consuming rodent feces. The differences in feeding abilities of the
larval and adult life history stages have profound consequences for their
resource use and foraging strategies, and hence the ecological role of dung
beetles. This principle and its ecological consequences should be explored in
other scarabaeids.
PMID- 29961181
TI - The Role and Influence of the Mother in the Development of the Fetus: Comparative
Study of Qur'an, Hadiths, and Modern Medical Perspectives.
AB - The creation and development of the fetus is one of the wonders of nature and
still has many unknowns. It was previously believed that the mother has no role
in fetus formation/development and only acts as a chamber. Today, we know that
the mother is involved in both formation and development of the fetus and even in
the future of the baby's life. In this article, the relationship between some
Qur'anic verses, Hadiths, and the results of new medical research on the
importance of mother's role in the development of the fetus and future of the
newborn life is discussed. It can be concluded that Qur'an and Hadiths are
consistent with modern science in the issue discussed.
PMID- 29961182
TI - Association between insomnia and type 2 diabetes mellitus in Han Chinese
individuals in Shandong Province, China.
AB - PURPOSE: Diabetes and sleep disorders are public health threats worldwide, but
the potential association between them is still unclear. METHODS: We conducted a
community-based cross-sectional study including 5078 participants (2665, 52.5%
male) to determine the association between insomnia and diabetes mellitus
prevalence. RESULTS: In patients with type 2 diabetes mellitus (T2DM) and
nondiabetic controls, the prevalence of insomnia was 20.2% (68/377) and 12.2%
(578/4741), respectively. The results showed that insomnia was associated with
T2DM after adjusting for age, sex, BMI, smoking, alcohol consumption, presence of
disease history (hypertension, dyslipidemia, stroke, cardiovascular diseases,
cancers), and depression (odds ratio [OR] = 1.31, 95% confidence interval [CI]
1.03-1.66). After stratifying by age and sex, insomnia was significantly
associated with diabetes mellitus only in the subgroup of middle-aged
participants (40-59 years) (OR = 1.61, 95% CI 1.16-2.23) and males (OR = 1.48,
95% CI 1.08-2.03) after controlling for the above covariates. CONCLUSIONS: This
study suggests that insomnia is independently and significantly associated with
diabetes mellitus in the northern Chinese population, especially in the 40-59
year-old age group and in males.
PMID- 29961183
TI - Combining Tumor Vaccination and Oncolytic Viral Approaches with Checkpoint
Inhibitors: Rationale, Pre-Clinical Experience, and Current Clinical Trials in
Malignant Melanoma.
AB - The field of tumor immunology has faced many complex challenges over the last
century, but the approval of immune checkpoint inhibitors (anti-cytotoxic T
lymphocyte-associated protein 4 [CTLA4] and anti-programmed cell death-1 [PD
1]/PD-ligand 1 [PD-L1]) and talimogene laherparepvec (T-VEC) for the treatment of
metastatic melanoma have awakened a new wave of interest in cancer immunotherapy.
Additionally, combinations of vaccines and oncolytic viral therapies with immune
checkpoint inhibitors and other systemic agents seem to be promising synergistic
strategies to further boost the immune response against cancer. These
combinations are undergoing clinical investigation, and if successful, will
hopefully soon become available to patients. Here, we review key basic concepts
of tumor-induced immune suppression in malignant melanoma, the historical
perspective around vaccine development in melanoma, and advances in oncolytic
viral therapies. We also discuss the emerging role for combination approaches
with different immunomodulatory agents as well as new developments in
personalized immunization approaches.
PMID- 29961184
TI - The epidemiology and survivorship of clear cell sarcoma: a National Cancer
Database (NCDB) review.
AB - PURPOSE: Clear cell sarcoma (CCS) is a rare soft tissue tumor thought to
originate from tendons and aponeuroses. This is the largest and most
comprehensive study of CCS to the best of our knowledge. In addition, this is the
first study to determine the estimated 10-year overall survival, specific
treatment modalities including neoadjuvant and adjuvant combinations, and sites
of distant metastasis in CCS utilizing a national database. METHODS: The National
Cancer Database (NCDB) was used to study 489 patients diagnosed with CCS from
2004 to 2014. Kaplan-Meier methods were used to estimate 5- and 10-year overall
survival, and log-rank tests were used to compare survival amongst stage.
RESULTS: Median age at diagnosis was 39 years. Males and females were equally
affected. Race distribution was 78% Caucasian and 15% Black. Most common primary
site was lower limb or hip (53%). Percentage of patients with distant organ
metastases was 15%, with lung being the most common site (4%). Median overall
survival was 57.2 months. Overall estimated 5- and 10-year survival was
approximately 50 and 38%, respectively. Approximate 5-year survival for Stages I
IV was 75, 65, 35, and 15%, respectively. Stages at disease presentation were 34%
at Stage I, 13% at Stage II, 16% at Stage III, and 38% at Stage IV. Surgery was
the most common form of treatment (83%); 34% received radiation and 20% received
chemotherapy. CONCLUSION: The 5-year overall survival for CCS in Stages III and
IV was much worse than Stages I and II. Overall estimated 5- and 10-year survival
was approximately 50 and 38%, respectively. Men and women were equally affected
and had a median age at diagnosis of 39 years. The most common tumor location was
lower limb and hip and the most common site of metastases was the lung.
PMID- 29961186
TI - Factors Associated with College Women's Personal and Parental Decisions to be
Vaccinated Against HPV.
AB - The human papillomavirus (HPV) is a public health concern because of its
association with cancer. HPV vaccine rates among college students remains low.
This is a critical catch-up age for individuals to receive the HPV vaccine and
research shows parents still play a role in college students' medical decision
making. Therefore, the purpose of this study was to examine factors related to
college women making a solo decision to initiate the HPV vaccination in
comparison to making a joint parent-daughter decision. Data collected using an
internet-delivered questionnaire were analyzed from 799 college women who had
initiated or completed the HPV vaccination. Multinomial logistic regression was
performed to compare study variables on who decided the participant should be
vaccinated (self-decision, parent-only decision, joint parent-daughter decision).
Participants who were older (OR 1.68, p < 0.001) and sexually active (OR 4.97, p
< 0.001) were significantly more likely to have made a solo decision to be
vaccinated. Participants who completed the HPV vaccination (OR 0.33, p < 0.001)
and those who talked with a parent about the HPV vaccine (OR 0.12, p < 0.001)
were significantly less likely to have made a solo decision to be vaccinated.
Findings indicate joint parent-daughter decisions may improve HPV vaccination
cycle completion.
PMID- 29961185
TI - New Developments in the Management of Cytomegalovirus Infection After
Transplantation.
AB - Cytomegalovirus (CMV) continues to be one of the most important pathogens that
universally affect solid organ and allogeneic hematopoietic stem cell transplant
recipients. Lack of effective CMV-specific immunity is the common factor that
predisposes to the risk of CMV reactivation and clinical disease after
transplantation. Antiviral drugs are the cornerstone for prevention and treatment
of CMV infection and disease. Over the years, the CMV DNA polymerase inhibitor,
ganciclovir (and valganciclovir), have served as the backbone for management,
while foscarnet and cidofovir are reserved for the management of CMV infection
that is refractory or resistant to ganciclovir treatment. In this review, we
highlight the role of the newly approved drug, letermovir, a viral terminase
inhibitor, for CMV prevention after allogeneic hematopoietic stem cell
transplantation. Advances in immunologic monitoring may allow for an
individualized approach to management of CMV after transplantation. Specifically,
the potential role of CMV-specific T-cell measurements in guiding the need for
the treatment of asymptomatic CMV infection and the duration of treatment of CMV
disease is discussed. The role of adoptive immunotherapy, using ex vivo-generated
CMV-specific T cells, is highlighted. This article provides a review of novel
drugs, tests, and strategies in optimizing our current approaches to prevention
and treatment of CMV in transplant recipients.
PMID- 29961187
TI - Effects of chromium picolinate supplementation on growth, body composition, and
biochemical parameters in Nile tilapia Oreochromis niloticus.
AB - A feeding trial was conducted to evaluate the effects of chromium picolinate (Cr
Pic) on growth performance, body composition, and biochemical parameters in Nile
tilapia Oreochromis niloticus. Five experimental diets were formulated with high
protein diet (HP), low-protein diet (LP), and LP + 0.6, 1.2, or 1.8 mg kg-1 Cr,
respectively. Each diet was randomly assigned to four replicate groups of 30 fish
per aquarium in a water-circulated rearing system for 60 days. Dietary 1.2 or 1.8
mg kg-1 Cr inclusion significantly affects the final body weight, weight gain
rate, specific growth rate, feed efficiency rate, and protein efficiency ratio of
tilapia compare to the LP diet. The Cr inclusion significantly decreased the
content of blood urea nitrogen and the blood glucose level generally with
increasing Cr inclusion levels. The Cr content of gill tissue was higher than
that of back muscle in all treatments, and the addition of 1.2 or 1.8 mg kg-1 Cr
significantly enhanced the Cr contents of back muscle. The cold stress test
results showed that adding Cr significantly enhanced the serum T3 concentration
and reduced the activity of serum creatine kinase and the serum cortisol level.
These results indicated that the supplementation of chromium picolinate can
improve the growth performance and reshape the serum protein and carbohydrate
metabolism profile and has the potentiality to alleviate the detrimental effects
of cold stress in Nile tilapia. The low-protein diet with 1.8 mg kg-1 Cr obtained
the same growth performance as the high-protein diet.
PMID- 29961188
TI - Anti-inflammatory activities of Ophiopogonis Radix on hydrogen peroxide-induced
cellular senescence of normal human dermal fibroblasts.
AB - Ophiopogonis Radix (Ophiopogon root), which nourishes the yin, has been used in
clinical practice to promote fluid secretion and to moisturize the lungs and skin
in traditional Chinese and Japanese (Kampo) medicine. To evaluate this
traditional medicinal effect, we investigated the anti-chronic inflammatory
effect of Radix Ophiopogonis on senescent cells. Conversely, although several
phenotypes of Ophiopogon japonicus Ker-Gawler (Liliaceae) are prevalent in Japan
and China, we used these Ophiopogon roots by considering them as one crude drug,
Ophiopogonis Radix. In this study, it was revealed that there are two chemotypes
(Types A and B) in the root of the original plant, O. japonicus.
Methylophiopogonanone A (compound 1) and methylophiopogonanone B (compound 2)
were isolated as index compounds from Type A and compound 1 and ophiopogonanone A
(compound 3) from Type B. In addition, ophiopogonin B (compound 4) was isolated
as the main steroidal saponin from both Type A and B. The results indicated that
two different methanol extracts (from Types A and B) and the main constituents of
O. japonicus (compound 1-4), significantly downregulated the expression of
interleukin (IL)-6 and IL-8, which were enhanced by senescent normal human dermal
fibroblasts. Moreover, the two different methanol extracts and compounds 1-4
decreased IL-6 production in a strong and concentration-dependent manner by the
ELISA method.
PMID- 29961190
TI - Optimising drug therapy for non-infectious uveitis.
AB - INTRODUCTION: Uveitis encompasses a wide variety of sight-threatening diseases
characterized by intraocular inflammation. It is often classified as infectious
and non-infectious uveitis. Unlike infectious uveitis, a distinct infectious
agent cannot be identified in non-infectious uveitis and disease origin is
usually autoimmune, drug related, or idiopathic. THE ISSUE AT HAND: Non
infectious uveitis can often have a relapsing-remitting course, making it
difficult to treat, and poses a significant challenge to ophthalmologists. The
autoimmune nature of non-infectious uveitis warrants the use of anti-inflammatory
and immunomodulatory agents for disease control. However, a subset of patients
has persistent or recurrent ocular inflammation despite appropriate treatment,
stressing the need for newer therapies aimed at more specific inflammatory
targets such as tumour necrosis factor (TNF) alpha agents, anti-interleukin
agents, and anti-interleukin receptor agents. OBJECTIVES: This article discusses
the various medical options available for the treatment of non-infectious uveitis
in the light of the most recent evidence. CONCLUSION: Successful management of
non-infectious uveitis requires the clinician carefully balance advantages and
disadvantages of each new and old therapy while considering individual
circumstances. Counselling regarding the benefits and complications of each
therapy can help patients make an informed choice.
PMID- 29961191
TI - Mst1 promotes cardiac ischemia-reperfusion injury by inhibiting the ERK-CREB
pathway and repressing FUNDC1-mediated mitophagy.
AB - Cardiac ischemia-reperfusion (I/R) injury results mainly from mitochondrial
dysfunction and cardiomyocyte death. Mitophagy sustains mitochondrial function
and exerts a pro-survival effect on the reperfused heart tissue. Mammalian STE20
like kinase 1 (Mst1) regulates chronic cardiac metabolic damage and autophagic
activity, but its role in acute cardiac I/R injury, especially its effect on
mitophagy, is unknown. The aim of this study is to explore whether Mst1 is
involved in reperfusion-mediated cardiomyocyte death via modulation of FUN14
domain containing 1 (FUNDC1)-related mitophagy. Our data indicated that Mst1 was
markedly increased in reperfused hearts. However, genetic ablation of Mst1 in
Mst1-knockout (Mst1-KO) mice significantly reduced the expansion of the cardiac
infarction area, maintained myocardial function and abolished I/R-mediated
cardiomyocyte death. At the molecular level, upregulation of Mst1 promoted ROS
production, reduced mitochondrial membrane potential, facilitated the leakage of
mitochondrial pro-apoptotic factors into the nucleus, and activated the caspase-9
related apoptotic pathway in reperfused cardiomyocytes. Mechanistically, Mst1
activation repressed FUNDC1 expression and consequently inhibited mitophagy.
However, deletion of Mst1 was able to reverse FUNDC1 expression and thus re
activate protective mitophagy, effectively sustaining mitochondrial homeostasis
and blocking mitochondrial apoptosis in reperfused cardiomyocytes. Finally, we
demonstrated that Mst1 regulated FUNDC1 expression via the MAPK/ERK-CREB pathway.
Inhibition of the MAPK/ERK-CREB pathway prevented FUNDC1 activation caused by
Mst1 deletion. Altogether, our data confirm that Mst1 deficiency sends a pro
survival signal for the reperfused heart by reversing FUNDC1-related mitophagy
and thus reducing cardiomyocyte mitochondrial apoptosis, which identifies Mst1 as
a novel regulator for cardiac reperfusion injury via modulation of mitochondrial
homeostasis.
PMID- 29961192
TI - Prognostic factors for short-term and long-term outcomes of gastric cancer
surgery for elderly patients: 10 years of experience at a single tertiary care
center.
AB - This retrospective study aimed to verify the short-term and long-term outcomes of
elderly patients who underwent gastric resection for gastric cancer and to
compare the results between younger and elderly patients. 222 Patients, who
underwent gastrectomy between January 2005 and December 2014, were divided into 2
groups: <= 75 years old (group A) and > 75 years (group B). The groups were
homogeneous except for more advanced pathological stage (p = 0.011) and higher
number of comorbidities in group B (p < 0.001) and a higher rate of neoadjuvant
or adjuvant complementary therapy in group A (p = 0.029 and p < 0.001).
Perioperative morbidity rates were 38.7 and 65.5% (p = 0.001), and mortality
rates were 2.5 and 7.9% (p = ns), respectively. The independent negative
prognostic factors for morbidity were age older than 75 years [odds ratio (OR)
2.7], multiple organ resection (OR 2.4), and male gender (OR 1.8). The 36-month
survival rates were 76.1% and 42.1% (p = 0.002) and disease-free survival rates
were 85% and 76.3% (p = 0.017), respectively. Surgical indications should not be
limited by age.
PMID- 29961189
TI - Lipid transport required to make lipids of photosynthetic membranes.
AB - Photosynthetic membranes provide much of the usable energy for life on earth. To
produce photosynthetic membrane lipids, multiple transport steps are required,
including fatty acid export from the chloroplast stroma to the endoplasmic
reticulum, and lipid transport from the endoplasmic reticulum to the chloroplast
envelope membranes. Transport of hydrophobic molecules through aqueous space is
energetically unfavorable and must be catalyzed by dedicated enzymes, frequently
on specialized membrane structures. Here, we review photosynthetic membrane lipid
transport to the chloroplast in the context of photosynthetic membrane lipid
synthesis. We independently consider the identity of transported lipids, the
proteinaceous transport components, and membrane structures which may allow
efficient transport. Recent advances in lipid transport of chloroplasts,
bacteria, and other systems strongly suggest that lipid transport is achieved by
multiple mechanisms which include membrane contact sites with specialized protein
machinery. This machinery is likely to include the TGD1, 2, 3 complex with the
TGD5 and TGD4/LPTD1 systems, and may also include a number of proteins with
domains similar to other membrane contact site lipid-binding proteins.
Importantly, the likelihood of membrane contact sites does not preclude lipid
transport by other mechanisms including vectorial acylation and vesicle
transport. Substantial progress is needed to fully understand all photosynthetic
membrane lipid transport processes and how they are integrated.
PMID- 29961193
TI - Low-Virulence Organisms and Periprosthetic Joint Infection-Biofilm Considerations
of These Organisms.
AB - PURPOSE OF REVIEW: The purpose of this manuscript is to provide a critical review
of peer-reviewed literature over the last 5 years related to low virulent
organisms associated with periprosthetic joint infection (PJI). We evaluated the
most common organisms, the diagnostic challenges, and the novel tools available
in the perioperative workup of PJI as well as the current understanding of how
biofilm potentiates the indolent clinical presentation and explore a possible
shift in the surgical management of these patients. RECENT FINDINGS: Biofilm
actively prevents macrophage phagocytosis by suppressing proinflammatory activity
through the recruitment of myeloid-derived suppressor cells. Given the
appropriate host and organism conditions, increased utilization of one-stage
exchange arthroplasty in the surgical treatment of these low virulent infections
may be on the rise. Biomarkers and molecular techniques offer encouraging results
to diagnose low virulent organisms and future research focused on the disruption
of biofilm may ultimately give rise to improved treatment strategies.
PMID- 29961194
TI - Preparation, characterization, and pharmacokinetics of liposomal docetaxel for
oral administration.
AB - A docetaxel (DTX) liposomal formulation composed of egg phosphatidylcholine,
sodium deoxycholate, and stearylamine was developed. Eudragit (0.5%) was coated
to deliver the drug to the region between the distal small intestine and the
colon. Lyophilized trehalose and mannitol were used as cryoprotectants because
they preserve the particle integrity and good appearance. In vitro release
studies showed that the amount of drug released from the coated liposomes was low
in solution 1, which simulated the pH condition of the stomach. Especially during
the average gastric emptying time, the amount of drug released decreased when
Eudragit was added. The plasma DTX concentration was evaluated in pharmacokinetic
studies. The plasma drug concentration after intravenous (i.v.) administration
decreased rapidly within 120 min. Free DTX formulated using Tween 80 and the
lyophilized Eudragit-coated liposomal formulation were compared after oral
administration. The oral liposomal formulation had a longer half-life (t1/2) and
three-fold higher oral bioavailability. Thus, lyophilized Eudragit-coated
liposomal DTX could be a promising therapy for various solid tumors to improve
patient convenience and quality of life.
PMID- 29961195
TI - Anti-inflammatory activity of compounds from the rhizome of Cnidium officinale.
AB - Five new compounds, 9,3'-dimethoxyhierochin A (1), 6-oxo-trans-neocnidilide (2),
(+/-)-(3E)-trans-6-hydroxy-7-methoxydihydroligustilide (3), (+/-)-cnidiumin (4),
and 6-(1-oxopentyl)-salicylic acid methyl ester (5), together with twenty known
compounds (6-25), were isolated from the rhizome of Cnidium officinale. The
chemical structures of new compounds were established by NMR spectroscopic
techniques, mass spectrometry, Mosher's method, and CD spectrum. Their anti
inflammatory activities were evaluated against lipopolysaccharide (LPS)-induced
nitric oxide (NO) production in macrophage RAW 264.7 cells. Compounds 7, 13, and
14 showed inhibitory effects with IC50 values of 5.1, 24.5, and 27.8 MUM,
respectively. In addition, compounds 7, 13, and 14 reduced LPS-induced inducible
nitric oxide synthase (iNOS) expression and cyclooxygenase-2 (COX-2) protein in a
concentration-dependent manner.
PMID- 29961196
TI - Crosstalk between cancer cells and endothelial cells: implications for tumor
progression and intervention.
AB - Communication between tumor cells and stromal cells is crucial to tumor
development and progression. Fibroblasts and macrophages are the most common
stromal cells in the tumor microenvironment. Endothelial cells are another type
of stromal cell in the tumor microenvironment required for angiogenesis via
interaction with tumor cells. Tumor angiogenesis provides not only oxygen and
nutrients for tumor cells but also the necessary anchorage to facilitate tumor
metastasis. The present review summarizes studies on the crosstalk between cancer
cells and endothelial cells with a focus on implications for tumor progression.
The following four categories are discussed in this review: (1) cell-cell
communication in tumor microenvironment; (2) induction of metastasis by
interaction between cancer cells and endothelial cells; (3) angiogenesis induced
by tumor cells; (4) therapeutic strategies targeting adhesion and signaling
molecules as well as chemokines. This review provides useful information
highlighting the process of cancer aggressiveness affected by the crosstalk
between cancer cells and endothelial cells, and suggests therapeutic strategies
against tumor progression.
PMID- 29961197
TI - Quality measures in ventral hernia repair: a systematic review.
AB - BACKGROUND: The US healthcare system is shifting towards reimbursement for
quality over quantity of care. Quality measures are tied to financial incentives
in these healthcare models. It is important that surgeons become familiar with
quality measures addressing ventral hernia repair and understand candidate
measures that may drive future quality measure development. STUDY DESIGN: We
performed a systematic review of society websites, quality measure databases, and
the literature (Pubmed, Embase/Scopus, and Google Scholar) for quality measures
addressing ventral hernia surgery. Clinical practice guidelines were included as
candidate quality measures. All measures were categorized as structure, process
or outcome according to Donabedian domains, as well as within the six National
Quality Strategy (NQS) domains. RESULTS: Thirty quality measures and candidate
measures were identified. Eight candidate measures from the American Hernia
Society addressed ventral hernia repair, and 22 quality measures in general
surgery were also relevant to ventral hernia repair. Of the candidate measures, 6
(75%) were outcome and 2 (25%) were process measures. Of existing general surgery
quality measures, 9 (41%) were outcome and 13 (59%) were process measures. No
structural measures were identified. Overall, the majority of measures addressed
NQS priorities of effective clinical care (33%) and patient safety (27%), while
few addressed other domains. CONCLUSION: Both the Donabedian domains of quality
and NQS priorities were unequally represented in the current measures addressing
ventral hernia repair. Recognizing and addressing the under-represented areas
will provide a more balanced framework for developing quality measures and ensure
that ventral hernia surgery is appropriately evaluated in value-based payment
models.
PMID- 29961198
TI - Strategies to reduce readmissions for hyponatremia after transsphenoidal surgery
for pituitary adenomas.
AB - PURPOSE: Disorders of water balance, particularly hyponatremia from altered
antidiuretic hormone (ADH) secretion, are a common post-operative complication of
transsphenoidal surgery (TSS). We present our results from implementation of a 2
week 1.5 liter/daily fluid restriction on readmission rates for hyponatremia.
METHODS: A retrospective chart review was performed on 295 patients that
underwent TSS for pituitary adenomas at the University of Colorado, between March
2014 and March 2017. Groups were divided into those before and after the
implementation of a two-week, 1.5 liter daily fluid restriction and measurement
of a serum sodium level 7 days (+/- 2 days) after discharge. A standard-of-care
approach for variable degrees of hyponatremia was also utilized to guide
hyponatremia management. Patient demographics, hospital course, post-operative
complication rates, and rates of hospital admissions for hyponatremia were then
evaluated. RESULTS: Readmissions for symptomatic hyponatremia within 30 days of
TSS occurred in 9 of 118 (7.6%) of patients prior to fluid restriction
implementation and in four of 169 (2.4%) of patients in the post-implementation,
fluid-restricted group (p-value = 0.04): a 70% reduction in hospitalizations. The
two groups were similarly matched for pituitary tumor sub-type, age and gender.
None of these factors were predictive for hyponatremia. Importantly, the mild
fluid restriction did not result in any hospital readmissions for hypernatremia.
CONCLUSIONS: Mild fluid restriction (to 1.5 liters daily), in addition to a
single post-operative serum sodium level, is an effective approach to preventing
readmission for hyponatremia after TSS for pituitary adenomas.
PMID- 29961199
TI - Application of gamma-aminobutyric acid increased the level of phytohormones in
Citrus sinensis.
AB - MAIN CONCLUSION: In the current study, we showed that exogenous GABA
supplementation increases the endogenous GABA level, several amino acids, and
phytohormones in citrus plants, suggesting that GABA works in harmony with
phytohormones. Gamma-aminobutyric acid (GABA) plays a key role in cytosolic
regulation of pH, controlling of carbon and nitrogen metabolism, and protection
against biotic and abiotic stresses. Although it is well-known that GABA is
implicated in plant defense and it could act as a signaling molecule, its effect
on phytohormones is not completely understood. In this study, we investigated the
effect of exogenous GABA on citrus phytohormones using gas chromatography-mass
spectrometry. A significant increase in endogenous GABA was observed in GABA
treated plants. The highest increase in GABA was recorded in plants treated with
10 mM 7 days post-treatment. In addition, we observed a moderate increase in
several amino acids including glycine, L-alanine, L-proline, L-asparagine, and L
glutamine. The levels of benzoic acid, cinnamic acid, salicylic acid, trans
jasmonic acid, indole acetic acid, indole propionic acid, and abscisic acid were
significantly increased in GABA-treated plants compared to the control. The gene
expression showed that GABA transaminase (GABA-T) and succinic semialdehyde
dehydrogenase (SSADH) were induced in GABA-treated plants, indicating a
conversion of GABA to succinate. In addition, the gene expression of the
regulatory enzymes of the TCA cycle (malate dehydrogenase and succinic
dehydrogenase) was upregulated in GABA-treated plants, indicating an induction of
respiration. In agreement with the chemical analysis, the gene expression results
showed that most of the genes implicated in the biosynthesis of phytohormones
were also upregulated in GABA-treated plants. Our results indicated that GABA
works in harmony with phytohormones and suggested that regulation of
phytohormones by exogenous GABA could play a key role in reducing plant stress.
PMID- 29961200
TI - Long-term nitrate removal through methane-dependent denitrification
microorganisms in sequencing batch reactors fed with only nitrate and methane.
AB - Denitrifying anaerobic methane oxidation (damo) bioprocesses can remove nitrate
using methane as the electron donor, which gains great concern due to the current
stringent discharge standard of nitrogen in wastewater treatment plants. To
obtain an engineering acceptable nitrogen removal rate (NRR) and demonstrate the
long-term stable ability of damo system under conditions of nitrate and methane,
two sequencing batch reactors (SBRs) fed with only nitrate and methane were
operated for more than 600 days at 30 degrees C. The NRR of 21.91 +/- 0.73 mg
NO3--N L-1 day-1 was obtained which is, to the best of our knowledge, the highest
rate observed in the literatures under such conditions. The temperature was found
to significantly affect the system performance. Furthermore, the microbial
community was analyzed by using real-time PCR technique. The results showed that
the microbial consortium contained damo archaea and bacteria. These two microbes
cooperated to maintain the long-term stability. And the number of damo archaea
was higher than that of damo bacteria with the ratio of 1.77. By using methane as
the electron donor, damo archaea reduced nitrate to nitrite coupled to methane
oxidation and damo bacteria reduce the generated nitrite to nitrogen gas. The
first step of nitrate to nitrite taken by damo archaea might be the limiting step
of this cooperation system. SBR could be a suitable reactor configuration to
enrich slow-growing microbes like damo culture. These results demonstrated the
potential application of damo processes for nitrogen removal of wastewater
containing low C/N ratios.
PMID- 29961201
TI - Hyperhomocysteinemia influenced malnutrition in Parkinson's disease patients.
AB - INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disease with many
motor and non-motor symptoms. Hyperhomocysteinemia is reported in many PD
patients. Homocysteine (Hcy) is reported to be a risk factor for some PD non
motor symptoms. AIM: The aim was to analyze Hcy level and its correlation with
physical activity and motor and some non-motor symptoms (depression and
cognition) in PD patients. PATIENTS AND METHODS: Patients were surveyed for
physical activity and demographic data. Blood samples were obtained for Hcy,
vitamin B12, and folic acid determination. The Mini Nutritional Assessment (MNA),
Unified Parkinson's Disease Rating Scale (UPDRS) parts III and IV, Hoehn and Yahr
(H&Y) Scale, Beck Depression Inventory (BDI), and Mini Mental State Examination
(MMSE) were used to assess nutritional status, disease stage, and motor and some
non-motor symptoms (depression and cognition) of PD in study patients. RESULTS:
We analyzed 34 PD patients. Elevated Hcy level was found in 70.6% of these
patients. Patients reporting regular exercise had lower Hcy level (p < 0.025).
Hcy level yielded a statistically significant correlation with MNA score (rs = -
0.510; p < 0.003), UPDRS part III (rs = 0.372; p < 0.030), vitamin B12 (rs = -
0.519; p < 0.002), and folic acid (rs = - 0.502; p < 0.003) but not with
cognition and depression. There were no statistically significant differences in
Hcy level for disease stage either for dyskinesia or "off" periods. CONCLUSION:
PD patients are at a risk of hyperhomocysteinemia. Regular physical activity
decreases Hcy level, whereas poor motor function increases it. There is
correlation between Hcy level and malnutrition in PD patients.
PMID- 29961202
TI - Singlet Oxygen Generating Properties of Different Sizes of Charged Graphene
Quantum Dot Nanoconjugates with a Positively Charged Phthalocyanine.
AB - Various sizes of graphene quantum dots (GQDs) denoted as GQD2, GQD6 and GQD10
(increasing in size) were non-covalently attached to 2,9,16,23-tetrakis[4-(N
methylpyridyloxy)]-phthalocyanine (ZnTPPcQ) to form GQDs-ZnTPPcQ nanoconjugates.
X-ray photoelectron spectroscopy (XPS) showed that increasing sizes of GQDs
decreases the atomic concentrations of oxygen, which leads to blue shift in
spectra of the GQDs. Relative to Pcs alone (0.03), the presence of GQDs improved
the singlet oxygen quantum yields with the following values: GQD2-ZnTPPcQ (0.17),
GQD6-ZnTPPcQ (0.27) and GQD10-ZnTPPcQ (0.11). GQD2-ZnTPPcQ nanoconjugate system
had the most ZnTPPcQ loading, but did not generate the most singlet oxygen
species due to aggregation. This study shows that, the quantity of oxygen, size
and quality of GQDs as well as amount of Pc loading are amongst the vital
properties to consider when constructing GQD-nanoconjugate systems with optimal
singlet oxygen quantum yields.
PMID- 29961203
TI - Excimer Emission of Acridine Orange Adsorbed on Gadolinium-Yttrium Orthovanadate
Nanoparticles.
AB - Studying the complexes of inorganic nanoparticles - organic dye molecules is of
great importance for their theranostics application. In this paper, we report
gadolinium-yttrium orthovanadate nanoparticles (VNPs) - Acridine Orange (AO)
complex formation in water solutions. To study the interactions between VNPs and
AO, the methods of steady-state and time-resolved spectroscopy were used. It was
shown that in aqueous solutions containing VNPs, AO aggregation takes place with
a sandwich-like stacking of AO molecules in the near-surface layer of VNPs. The
VNPs-AO complex formation causes significant changes in the AO fluorescence
spectrum, namely, the appearance of a new broad, structureless band in the long
wavelength spectral edge, which was not observed in AO spectrum in a pure water
solution. By analyzing of the absorption, fluorescence excitation spectra and
fluorescence decay, the static excimer origin of the long-wavelength fluorescence
band has been established.
PMID- 29961204
TI - The Time-Resolved Fluorescence Stokes Shift of Cucurbit[6]Uril Complexes with a
Pyridinium Styryl Dye.
AB - The time-resolved Stokes shift of fluorescence of styryl dye, trans-4-[4
(dimethylamino)-styryl]-1-methylpyridinium iodide (DASPI), and its host-guest
complexes with cucurbit[6]uril (CB[6]) was studied by up-conversion technique on
a 5 ps time scale. In all cases, the solvation time correlation function - that
describes relaxation of the fluorescent state - contains two components. The time
constant of the first component, which is related to the vibrational relaxation
of the dye cation, increases from 118 fs without CB[6] to 224 fs in the presence
CB[6]. It suggests the production of CB[6] complexes to disturb the hydrogen-bond
net in the vicinity of DASPI cation. The time constant of the second component,
which is associated with solvation, changes from 0.81 ps without CB[6] to 1.15 ps
in the presence of the cavitand. The observed increase can be related to the
displacement of the dye cation deeper into CB[6] that allows considering DASPI
CB[6] complexes as a light-controlled molecular machine with a response time on
the picosecond scale.
PMID- 29961205
TI - Spectroscopic, Computational, Antimicrobial, DNA Interaction, In Vitro Anticancer
and Molecular Docking Properties of Biochemically Active Cu(II) and Zn(II)
Complexes of Pyrimidine-Ligand.
AB - Biochemically active Cu(II) and Zn(II) complexes [CuL(ClO4)2(1) and
ZnL(ClO4)2(2)] have been synthesized from N,N donor Schiff base ligand L derived
from4,6-dichloropyrimdine-5-carboxaldehyde with 4-(2-aminoethyl)morpholine. The
L, complexes 1 and 2 have been structurally characterized by elemental analysis,
1H-NMR, FTIR, MS, UV-Visible and ESR techniques. The results obtained from the
spectral studies supports the complexes 1 and 2 are coordinated with L through
square planar geometry. DFT calculations results supports, the ligand to metal
charge transfer mechanism can occur between L and metal(II) ions. The
antimicrobial efficacy results have been recommended that, complexes 1 and 2 are
good anti-pathogenic agents than ligand L. The interaction of complexes 1 and 2
with calf thymus (CT) DNA has been studied by electronic absorption, viscometric,
fluorometric and cyclic voltammetric measurements. The calculated Kb values for
L, complexes 1 and 2 found from absorption titrations was 4.45 * 104, L; 1.92 *
105, 1 and 1.65 * 105, 2. The Ksv values were found to be 3.0 * 103, 3.68 *
103and 3.52 * 103 for L, complexes 1 and 2 by using competitive binding with
ethidium bromide (EB). These results suggest that, the compounds are interacted
with DNA may be electrostatic binding. The molecular docking studies have been
carried out to confirm the interaction of compounds with DNA. Consequently, in
vitro anticancer activities of L, complexes 1 and 2 against selected cancer (lung
cancer A549, liver cancer HepG2 and cervical carcinoma HeLa) and normal (NHDF)
cell lines were assessed by MTT assay.
PMID- 29961206
TI - Engineering E. coli cell surface in order to develop a one-step purification
method for recombinant proteins.
AB - Sortases are enzymes mostly found in Gram-positive bacteria which cleave proteins
site-specifically. This feature makes them a promising tool in molecular biology
and biotechnology. In this study, using bacterial surface display of recombinant
proteins and ability of sortase A in site-specifically cleavage of the amino acid
sequences, a novel method for one-step purification of recombinant proteins was
developed. Using computational program tools, a chimeric protein containing a
metallothionein (mt) and chitin binding domain (ChBD) was attached to the C
terminal domain of the truncated outer membrane protein A (Lpp'-ompA) using
sortase recognition site (amino acid residues: LPQTG) as a separator. The
structure of the chimeric protein was simulated using molecular dynamics to
determine if the LPQTG motif is accessible to the sortase active site. The
designed chimeric protein was expressed and purified. The purified chimeric
protein was also displayed on the surface of E. coli cells. Both purified
chimeric protein and the E. coli cells displaying Lpp'-ompA-mt-ChBD carrier
protein were then treated with sortase to evaluate the efficiency of sortase
mediated cleavage of purified chimeric protein as well as surface displayed
chimeric protein. It is shown that mt-ChBD protein was successfully cleaved and
dissociated from Lpp'-ompA carrier and released into the medium after treatment
with sortase in both recombinant protein and surface displayed-chimeric protein.
The experimental results confirmed the molecular dynamics analysis results. The
presented method could be regarded as a novel strategy for one step expression
and purification of recombinant proteins.
PMID- 29961209
TI - Dual antiretroviral therapy with tenofovir (TDF) and darunavir/ritonavir
(DRV/RTV) in an HIV-1 positive patient: a case report, review, and meta-analysis
of the literature on dual treatment strategies using protease inhibitors in
combination with an NRTI.
AB - BACKGROUND: Here, we report the case of an HIV positive patient under a dual
antiretroviral drug regimen with tenofovir disoproxil and darunavir/ritonavir
with stable clinical, virological, and immunological response over 126 weeks.
Dual antiretroviral therapy has the advantage of reduced toxicity and lower
health care costs, treatment failure and fostering drug resistance are perceived
risks. Optimal drug combinations and indication criteria for dual treatment
remain controversial. Nevertheless, first clinical trials indicate non
inferiority for combinations of nucleoside reverse transcriptase inhibitors and
protease inhibitors. This case presents the combination of tenofovir disoproxil
in combination with a protease inhibitor as a new potential dual treatment
regimen. METHOD: We performed a systematic literature search and meta-analysis of
trials comparing dual to triple ART. RESULTS: Literature review revealed nine
studies in which dual therapy with a protease inhibitor and an NRTI was compared
to triple therapy. We performed a meta-analysis of six trials that reported a 48
week follow-up. In treatment-naive patients as well when ART switch was assessed,
there was no difference in the treatment success in patients with dual ART versus
triple. CONCLUSION: We conclude that dual therapy with a protease inhibitor and
NRTI is safe and effective. The use of tenofovir in dual treatment as described
in our case needs to be assessed in future clinical trials.
PMID- 29961207
TI - The NBA and Youth Basketball: Recommendations for Promoting a Healthy and
Positive Experience.
AB - Participation in sports offers both short-term and long-term physical and
psychosocial benefits for children and adolescents. However, an overemphasis on
competitive success in youth sports may limit the benefits of participation, and
could increase the risk of injury, burnout, and disengagement from physical
activity. The National Basketball Association and USA Basketball recently
assembled a group of leading experts to share their applied research and
practices to address these issues. This review includes the group's analysis of
the existing body of research regarding youth sports participation and the
related health, performance, and psychosocial outcomes. Based upon this, age
specific recommendations for basketball participation are provided that aim to
promote a healthy and positive experience for youth basketball players.
PMID- 29961208
TI - Are the Mechanical or Material Properties of the Achilles and Patellar Tendons
Altered in Tendinopathy? A Systematic Review with Meta-analysis.
AB - BACKGROUND: Changes in the mechanical behaviour of the Achilles and patellar
tendons in tendinopathy could affect muscle performance, and have implications
for injury prevention and rehabilitation strategies. OBJECTIVES: To determine the
effect of clinically diagnosed tendinopathy on the mechanical and material
properties of the Achilles tendon (AT) and patellar tendon (PT). DESIGN:
Systematic review with meta-analysis. METHODS: A search of electronic databases
(SPORTDiscus, CINAHL, PubMed, ScienceDirect and Google Scholar) was conducted to
identify research articles that reported local and global in vivo mechanical
(e.g. strain, stiffness) and/or material properties (e.g. modulus) of the AT
and/or PT in people with and without tendinopathy. Effect sizes and corresponding
95% confidence intervals for individual studies were calculated for tendon
strain, stiffness, modulus and cross-sectional area. RESULTS: Eighteen articles
met the inclusion criteria (AT only = 11, PT only = 5, AT and PT = 2). There was
consistent evidence that the reported AT strain was higher in people with
tendinopathy, compared to asymptomatic controls. People with Achilles
tendinopathy had a lower AT global stiffness, lower global modulus and lower
local modulus, compared to asymptomatic controls. In contrast, there was no clear
and consistent evidence that the global or local mechanical or material
properties of the PT are altered in tendinopathy. CONCLUSIONS: The in vivo
mechanical and material properties of the Achilles tendon-aponeurosis are altered
in tendinopathy, compared to asymptomatic tendons. Despite a similar clinical
presentation to Achilles tendinopathy, patellar tendinopathy does not appear to
alter the tensile behaviour of the PT in vivo.
PMID- 29961210
TI - Is there any evidence that AGE/sRAGE is a universal biomarker/risk marker for
diseases?
AB - Advanced glycation end products (AGE) and its cell-bound receptor called receptor
for AGE (RAGE) are implicated in the pathogenesis of numerous diseases. Soluble
receptor for AGE (sRAGE) counteracts the adverse effects of AGE-RAGE interaction
by competing with RAGE for binding with AGE. Low levels of serum sRAGE have been
proposed as a biomarker for diseases. However, the serum levels of sRAGE in
diabetes and end-stage renal disease (ESRD) are elevated. Thus, low levels of
sRAGE cannot be a universal biomarker. An elevated ratio of AGE/sRAGE was then
proposed as a universal biomarker. However, evidence was not provided for this
new biomarker. The objective of this paper is to provide evidence in support of
elevated AGE/sRAGE being a universal biomarker. The data for serum levels of AGE,
sRAGE, and ratio of AGE/sRAGE were collected from patients with low serum sRAGE
[non-ST-elevation myocardial infarction (NSTEMI), hyperthyroidism (HT), thoracic
aortic aneurysm (TAA),and hypercholesterolemia (HC)], and with high serum levels
of sRAGE [type-2 diabetes (T2D) and ESRD], and control subjects. The serum levels
of AGE and ratio of AGE/sRAGE were higher in all types of patients irrespective
of low or high serum sRAGE as compared to control subjects. Reasons are provided
as to why AGE or sRAGE individually cannot be considered as a universal
biomarker. In conclusion, the evidence supports the validity of the high ratio
AGE/sRAGE as a universal biomarker/risk marker for diseases.
PMID- 29961211
TI - Basement membrane extract attenuates the more malignant gene expression profile
accentuated by fibronectin in prostate cancer cells.
AB - Prostate cancer (PCa) has high mortality rates, with most of the deaths resulting
from the development of metastasis. Fibronectin (FN) plays key roles in cell
adhesion and affects the migratory behavior of cells. In the tumor
microenvironment and also in the blood plasma during metastasis, FN displays
increased expression, however its role in prostate cancer remains poorly
understood. This study aimed to unveil the specific roles of FN as a soluble
component, alone or in combination with a complex basement membrane. To
investigate the impact of FN in neoplastic prostate cells, we evaluated the gene
expression of LNCaP cells by RT-qPCR after exposure to soluble FN (25 ug/mL)
either alone or in combination with a basement membrane. When FN was the
predominant matrix element, such as in blood plasma, PCa tumor cells increased
their expression of genes related to an invasive behavior and resistance to
apoptosis, including CDH2, ITGA5, AKT1, and BCL2. However, the combined presence
of FN and a complex basement membrane had the opposite effect on LNCaP cells, in
which the expression levels of CDH2, ITGA5, AKT1, and BCL2 were reduced.
Hierarchical clustering analysis with LNCaP and RWPE-1 cells showed that LNCaP
cells exposed to an enriched extracellular matrix displayed an expression pattern
more similar to that shown by RWPE-1 cells, a cell line that illustrates
characteristics of the normal prostate epithelium. These findings provide the
groundwork for future studies addressing the role of FN in tumor growth,
particularly in the context of cancer evolution/progression from a solid primary
tumor to a transitory circulating state.
PMID- 29961212
TI - Antibacterial Activity of Vancomycin Encapsulated in Poly(DL-lactide-co
glycolide) Nanoparticles Using Electrospraying.
AB - Vancomycin is often used to treat infections caused by beta-lactam-resistant
bacteria. However, methicillin-resistant strains of Staphylococcus aureus (MRSA)
acquired resistance to vancomycin, rendering it less effective in the treatment
of serious infections. In the search for novel antibiotics, alternative delivery
mechanisms have also been explored. In this study, we report on the encapsulation
of vancomycin in PLGA [poly(DL-lactide-co-glycolide)] nanoparticles by
electrospraying. The nanoparticles were on average 247 nm in size with small bead
formations on the surface. Clusters of various sizes were visible under the SEM
(scanning electron microscope). Vancomycin encapsulated in PLGA (VNP) was more
effective in inhibiting the growth of S. aureus Xen 31 (MRSA) and S. aureus Xen
36 than un-encapsulated vancomycin. Encapsulated vancomycin had a minimum
inhibitory concentration (MIC) of 1 MUg/mL against MRSA compared to 5 MUg/mL of
free vancomycin. At least 70% (w/w) of the vancomycin was encapsulated. Thirty
percent of the vancomycin was released within the first 144 h, followed by slow
release over 10 days. Vancomycin encapsulated in PLGA nanoparticles may be used
to treat serious infections.
PMID- 29961213
TI - Teeth whitening with 6% hydrogen peroxide and its impact on quality of life: 2
years of follow-up.
AB - This study aimed to evaluate color longevity after 2 years of whitening gel (6%
hydrogen peroxide (HP), blue LED/infrared laser activation system) in comparison
to a control 35% concentration in a split-mouth study and investigate the long
term effect on quality of life (QOL).Thirty-one patients were treated. Whitening
using 6% or 35% HP gel was performed on half of the upper jaw in each patient.
The color was measured at baseline and 1 week, 1 month, 1 and 2 years after
treatment using the Easyshade Vita spectrophotometer and the Vita Bleached and
Vita Classical Shade Guides organized by value. During 2 years of follow-up,
color was evaluated before and after dental prophylaxis. Oral Health of Impact
Profile (OHIP 14) and Psychosocial Impact Dental Aesthetics Questionnaire (PIDAQ)
surveys measured QOL. Nineteen patients were evaluated at the 2-year follow-up.
Significant differences in DeltaE were measured between the two groups at all
time points (p < 0.05). No significant differences in DeltaSGU were observed at
any time point (p > 0.05). The positive effect of bleaching on QOL was maintained
in patients treated with a low concentration of the whitening gel. The two
compounds remained effective after 2 years. An objective color difference was
found between the groups, but no difference was observed in subjective reports.
The positive effect on QOL remained after 2 years of follow-up in this cohort of
patients. ClinicalTrials.gov identifier NCT02353611.
PMID- 29961214
TI - Between the Reasonable and the Particular: Deflating Autonomy in the Legal
Regulation of Informed Consent to Medical Treatment.
AB - The law of informed consent to medical treatment has recently been extensively
overhauled in England. The 2015 Montgomery judgment has done away with the long
held position that the information to be disclosed by doctors when obtaining
valid consent from patients should be determined on the basis of what a
reasonable body of medical opinion agree ought to be disclosed in the
circumstances. The UK Supreme Court concluded that the information that is
material to a patient's decision should instead be judged by reference to a new
two-limbed test founded on the notions of the 'reasonable person' and the
'particular patient'. The rationale outlined in Montgomery for this new test of
materiality, and academic comment on the ruling's significance, has focused on
the central ethical importance that the law now (rightfully) accords to respect
for patient autonomy in the process of obtaining consent from patients. In this
paper, we dispute the claim that the new test of materiality articulated in
Montgomery equates with respect for autonomy being given primacy in re-shaping
the development of the law in this area. We also defend this position, arguing
that our revised interpretation of Montgomery's significance does not equate with
a failure by the courts to give due legal consideration to what is owed to
patients as autonomous decision-makers in the consent process. Instead,
Montgomery correctly implies that doctors are ethically (and legally) obliged to
attend to a number of relevant ethical considerations in framing decisions about
consent to treatment, which include subtle interpretations of the values of
autonomy and well-being. Doctors should give appropriate consideration to how
these values are fleshed out and balanced in context in order to specify
precisely what information ought to be disclosed to a patient as a requirement of
obtaining consent, and as a core component of shared decision-making within
medical encounters more generally.
PMID- 29961215
TI - A novel mechanism of autophagy-associated cell death of vasopressin neurons in
familial neurohypophysial diabetes insipidus.
AB - Familial neurohypophysial diabetes insipidus (FNDI), characterized by delayed
onset progressive polyuria and loss of arginine vasopressin (AVP) neuron, is an
autosomal dominant disorder caused by AVP gene mutations. We previously generated
a knock-in mouse model for FNDI, which recapitulated the phenotype of human FNDI.
To address the mechanisms underlying AVP neuron loss, we subjected FNDI mice to
intermittent water deprivation, which accelerated the phenotype and induced AVP
neuron loss within a relative short period. Electron microscopic analyses
revealed that aggregates were confined to a sub-compartment of the endoplasmic
reticulum (ER), ER-associated compartment (ERAC), in AVP neurons of FNDI mice
under normal conditions. In contrast, aggregates scattered throughout the dilated
ER lumen, and phagophores, autophagosome precursors, emerged and surrounded the
ER containing scattered aggregates in FNDI mice subjected to water deprivation
for 4 weeks, suggesting that failure of ERAC formation leads to autophagy
induction for degradation of aggregates. Furthermore, the cytoplasm was entirely
occupied with large vacuoles in AVP neurons of FNDI mice subjected to water
deprivation for 12 weeks, at which stage 30-40% of AVP neurons were lost. Our
data demonstrated that although autophagy should primarily be a protective
mechanism, continuous autophagy leads to gradual loss of organelles including ER,
resulting in autophagy-associated cell death of AVP neurons in FNDI mice.
PMID- 29961216
TI - MicroRNAs in the hypothalamic control of energy homeostasis.
PMID- 29961217
TI - Efficient generation of functional cardiomyocytes from human umbilical cord
derived virus-free induced pluripotent stem cells.
AB - We have previously demonstrated that human umbilical cord-derived mesenchymal
stem cells (UC-MSCs) can differentiate into cardiomyocyte-like cells. However, no
contracting cells were observed during differentiation. In this study, we
generated induced pluripotent stem cells (iPSCs) from UC-MSCs using mRNA
reprogramming and focused on the differentiation of reprogrammed iPSCs into
functional cardiomyocytes. For cardiac differentiation, the spontaneously
contracting cell clusters were present on day 8 of differentiation.
Immunostaining studies and cardiac-specific gene expression confirmed the
cardiomyocyte phenotype of the differentiated cells. Electrophysiology studies
indicated that iPSCs derived from UC-MSCs had a capacity for differentiation into
nodal-, atrial-, and ventricular-like phenotypes based on action potential
characteristics, and the derived cardiomyocytes exhibited responsiveness to beta
adrenergic and muscarinic stimulations. Moreover, the derived cardiomyocytes
displayed spontaneous intracellular Ca2+ transients. These results demonstrate
that functional cardiomyocytes can be generated from reprogrammed UC-MSCs, and
the methodology described here will serve as a useful protocol to obtain
functional cardiomyocytes from human mesenchymal stem cells.
PMID- 29961218
TI - Expression of beta-hexosaminidase in the male reproductive system of the lizard,
Eutropis carinata. (Reptilia, Squamata) (Schneider, 1801).
AB - Beta-hexosaminidase (Hex) is the major lysosomal enzyme associated with the event
of fertilization. In this study, we have analyzed the distribution of Hex in the
testis and the epididymis of the lizard, Eutropis carinata by a polyclonal
antibody of beta-hexosaminidase isoform (Hex A). Presence of Hex in the
epididymis was performed by Western blotting. The result reveals that Hex A is
present in the epididymal epithelium, lumen as well as spermatozoa. The
anatomical distribution of Hex was studied by immunohistochemical localization.
The study reveals that Hex is intensely stained in the epithelium of anterior and
middle regions of the epididymis, whereas, posterior epididymal epithelium shows
moderate staining. In addition, seminiferous epithelium of the testis shows
staining for Hex. But lumen of the testis did not show any reaction for Hex.
Further, immunohistochemical localization of Hex on the spermatozoa from the
testis and different regions of the epididymis revealed that the Hex from the
testis did not show any staining; the epididymal epithelium is moderately
localized in the spermatozoa of the anterior region and gradually increases in
the intensity in the spermatozoa of the posterior region of the epididymis. This
indicates that the Hex is released from the epididymal epithelium and binds to
the spermatozoa, and in the lumen, it gradually increases from anterior to the
posterior region of the epididymis. The result also suggests that Hex A bound to
the epididymal spermatozoa originates from the epididymis and not from the
testis. The regional difference in the expression of Hex in the epididymis of the
lizard, E. carinata, indicates the possible site of secretion of this enzyme.
PMID- 29961219
TI - An approach to the heating dynamics of residues from greenhouse-crop plant
biomass originated by tomatoes (Solanum lycopersicum, L.).
AB - The most representative of greenhouse-crop plant biomass residues of tomatoes
(Solanum lycopersicum L.) were selected for this study by using X-ray
fluorescence spectrometry (XRF) and X-ray powder diffraction (XRD). The heating
dynamics in air in the 600-1150 degrees C range of these residues for the
production of renewable energy and the resultant ashes have been investigated. A
total of 11 elements were determined by XRF in the biomass ashes and some minor
elements. The content of alkaline elements and chlorides decreased as increasing
heating temperature and disappeared at 1150 degrees C. Alkaline salts, NaCl and
KCl, were volatilized by heating since 800 degrees C. The total contents of S
and P in the biomass ashes were associated to CaSO4, and a complex phosphate
identified by XRD. CaCO3 present at 600 degrees C was decomposed to CaO with
disappearance at 1000 degrees C. By heating, new silicates were formed by solid
state reactions in the biomass residue. The minor elements have been found in a
relative proportion lower than 0.9 wt.% and they characterized the obtained
ashes, with potential use as micronutrients.
PMID- 29961221
TI - Varying concentrations of soil chromium (VI) for the exploration of tolerance
thresholds and phytoremediation potential of the oregano (Origanum vulgare).
AB - Varying concentrations of soil Cr(VI) were used in order to explore the tolerance
thresholds and phytoremediation potential of Greek oregano (Origanum vulgare), in
a pot experiment conducted outdoors. Oregano exhibited a rather exceptional
capacity to bioaccumulate Cr in both the aerial part (up to 1200 mg of total Cr
kg-1 DM) and the root-reaching 4300 mg kg-1 DM when grown in soil [Cr(VI)] of 150
200 mg kg-1. Plant responses indicated that there was a threshold set at 100 mg
Cr(VI) kg-1 in the soil, above which the following results were recorded: (i) a
restriction of Cr translocation from below- to above-ground plant part, (ii) a
raise of the soil-to-root Cr transfer, and (iii) the Cr(III) evolution from the
reduction of Cr(VI) was significantly decelerated in the root and accelerated in
the aerial part. Soil [Cr] that surpassed this threshold challenged plant
tolerance, resulting in a dose-dependent reduction of growth and antioxidant
phenolics pool. Nonetheless, the significant Cr uptake capacity at plant level
accounted for the considerably short remediation time (i.e., 29 years at soil
[Cr(VI)] of 150 mg kg-1) calculated according to these results. The overall
performance of oregano indicated that phytoremediation would be feasible at sites
with Cr contamination levels ranging within the above-defined thresholds.
PMID- 29961220
TI - Association between prenatal nickel exposure and preterm low birth weight:
possible effect of selenium.
AB - There is a proposed link between prenatal nickel (Ni) exposure and preterm low
birth weight (PLBW); however, this association remains unclear. Selenium (Se) may
modify this relationship by protecting against Ni toxicity. Concentrations of Ni
and Se were measured in urine samples collected from 408 pregnant women (102 PLBW
cases and 306 matched controls) in China. Conditional logistic regression was
utilized to explore the association between Ni levels and PLBW, as well as the
effect modification by Se on this association. A significant association was
observed between higher maternal urinary Ni levels and risk of PLBW [adjusted
odds ratio (OR) = 2.80 (95% confidence interval (CI): 1.44, 5.44) for the highest
tertile], and this association was more apparent among female infants than that
among male infants. Further analyses showed that mothers with high urinary Ni and
low urinary Se levels had a significantly increased risk for PLBW [adjusted OR =
2.87 (95% CI: 1.09, 7.56)] compared with the mothers with low urinary Ni and high
urinary Se levels. Our study indicates that prenatal exposure to Ni was a risk
factor for PLBW. Se might provide protection against the toxicity of Ni.
PMID- 29961222
TI - Impact of waste-derived organic and inorganic amendments on the mobility and
bioavailability of arsenic and cadmium in alkaline and acid soils.
AB - In agriculture, more and more frequently waste-derived amendments are applied to
soil to improve physical and chemical properties. Nevertheless, in soils polluted
by potentially toxic metal(loid)s, this agricultural practice may significantly
affect the mobility and bioavailability of pollutants modifying the risks for
biota and human health. This work was aimed to assess the influence of poultry
manure, biochar and coal fly ash on the mobility and bioavailability of As and Cd
spiked in two Australian soils with different pH and texture: Mount Gambier (MGB)
alkaline sandy clay loam and Kapuda (KPD)-acid loamy sand. After 4 weeks of
incubation from spiking and another 4 weeks from amendment addition, the soils
were analysed for pH and amounts of As and Cd in pore-water and following 1 M
NH4NO3 extraction. Bioavailable amounts were assessed by plant uptake, using Zea
mays L. as test crop. In the alkaline MGB soil, the availability of Cd was
reduced, while that of As increased. An opposite behaviour was observed in the
acid KPD soil. All amendments, when added to KPD soil, increased pH and
consequently reduced the mobility of Cd and increased the mobility of As. In MGB,
the amendment addition had an effect only on As mobility and bioavailability,
which increased likely as a result of the increased competition for adsorption
with DOC released by organic compounds. These trends were confirmed by the
amounts of Cd and As uptaken by maize plants.
PMID- 29961223
TI - The spatial distribution of phosphorus and their correlations in surface
sediments and pore water in Lake Chaohu, China.
AB - The study presents the spatial distribution of different forms of phosphorus in
the sediments in Lake Chaohu, a large eutrophic Chinese lake, and their
correlation with phosphorus content in pore water. The sediment and pore water
samples were taken from 19 sampling sites. A sequential extraction was used to
determine the contents of different forms of phosphorus in the sediments. The
compositions and spatial distribution of different forms of phosphorus in the
sediments and their correlation with orthophosphate and total phosphorus content
in the pore water were studied. The following results were obtained: (1) the mean
content of total phosphorus was 474.7 +/- 20.5 mg/kg, with 390.8 +/- 82.4 mg/kg
for the eastern lake (N = 5), 469.0 +/- 53.9 mg/kg for the western lake (N = 5),
and 524.5 +/- 185.3 mg/kg for rivers (N = 9); (2) the order of the proportions of
the different forms of phosphorus was occluded phosphorus (Oc-P, 52.4%) > debris
phosphorus (De-P, 14.2%) > auto-calcium-bound phosphorus (ACa-P, 13.5%) >
aluminum-bound phosphorus (Al-P, 9.8%) > organic phosphorus (Or-P, 6.8%) >
exchangeable phosphorus (Ex-P, 2.1%) > iron-bound phosphorus (Fe-P, 1.3%); (3) Ex
P, Al-P, and Fe-P had significantly positive correlations with orthophosphate and
total phosphorus content in pore water, which showed that these forms of
phosphorus were released more easily and had an indirect impact on lake
eutrophication.
PMID- 29961224
TI - Ecotoxicological evaluation of electrochemical oxidation for the treatment of
sanitary landfill leachates.
AB - In this study, the efficiency of electrochemical oxidation to treat a sanitary
landfill leachate was evaluated by the reduction in physico-chemical parameters
and in ecotoxicity. The acute toxicity of the sanitary landfill leachates, before
and after treatment, was assessed with the model organism Daphnia magna.
Electrochemical oxidation treatment was effective in the removal of organic load
and ammonium nitrogen and in the reduction of metal ions concentrations.
Furthermore, a reduction of 2.5-fold in the acute toxicity towards D. magna after
36 h of treatment was noticed. Nevertheless, the toxicity of the treated leachate
is still very high, and further treatments are necessary in order to obtain a non
toxic effluent to this aquatic organism. Toxicity results were also compared with
others described in the literature for different leachate treatments and test
organisms.
PMID- 29961225
TI - Silicon improves salt tolerance of Glycyrrhiza uralensis Fisch. by ameliorating
osmotic and oxidative stresses and improving phytohormonal balance.
AB - Si has a beneficial effect on improving plant tolerance to salt stress.
Nevertheless, the mechanisms of Si in mediating the stress responses are still
poorly understood. Glycyrrhiza uralensis Fisch. (G. uralensis), a well-known
medicinal plant, possesses vast therapeutic potentials. In the present study, a
pot experiment was conducted to investigate the long-term effects of Si on growth
and physiobiochemical characteristics in 2-year-old G. uralensis subjected to
different levels of salinity. Si markedly affected G. uralensis growth in a salt
concentration-dependent manner and had no effect on G. uralensis growth under 6
g/kg NaCl. However, it partly reversed the reduction effect induced by 9 g/kg
NaCl. In addition, Si significantly increased the contents of soluble sugar and
protein but deceased proline content and thus increased water relations; Si
markedly increased the activities of SOD, peroxidase, and CAT and further
resulted in decreased MDA content and membrane permeability. Moreover, Si altered
the levels of phytohormones and their balances. With correlation analysis and
principal component analysis (PCA), root biomass had a significant negative
correlation with MDA and membrane permeability while a positive correlation with
indole-3-acetic acid and GA3. The PCA partitioned the total variance into three
PCs contributing maximum (88.234%) to the total diversity among the salt stress
with or without Si due to the study of various traits. In conclusion, Si exerts a
beneficial property on salt-induced harmful effects in G. uralensis by relieving
osmotic stress, improving water relations, and alleviating oxidative stress;
thus, altering the levels and balance of phytohormones results in improved growth
of salt-stressed G. uralensis.
PMID- 29961227
TI - Editorial to accompany the discussion paper 'Survival models and health
sequences' by Walter Dempsey and Peter McCullagh.
PMID- 29961226
TI - Determination of carbamazepine in urine and water samples using amino
functionalized metal-organic framework as sorbent.
AB - A stable and porous amino-functionalized zirconium-based metal organic framework
(Zr-MOF-NH2) containing missing linker defects was prepared and fully
characterized by FTIR, scanning electron microscopy, powder X-ray diffraction,
and BET surface area measurement. The Zr-MOF-NH2 was then applied as an adsorbent
in pipette-tip solid phase extraction (PT-SPE) of carbamazepine. Important
parameters affecting extraction efficiency such as pH, sample volume, type and
volume of eluent, amount of adsorbent, and number of aspirating/dispensing cycles
for sample solution and eluent solvent were investigated and optimized. The best
extraction efficiency was obtained when pH of 100 uL of sample solution was
adjusted to 7.5 and 5 mg of the sorbent was used. Eluent solvent was 10 uL
methanol. Linear dynamic range was found to be between 0.1 and 50 ug L-1 and
limit of detection for 10 measurement of blank solution was 0.05 ug L-1. This
extraction method was coupled to HPLC and was successfully employed for the
determination of carbamazepine in urine and water samples. The strategy combined
the advantages of fast and easy operation of PT-SPE with robustness and large
adsorption capacity of Zr-MOF-NH2.
PMID- 29961228
TI - Less radiation, same quality: contrast-enhanced multi-detector computed
tomography investigation of thoracic lymph nodes with one milli-sievert.
AB - PURPOSE: Mediastinal, hilar, and peripheral pulmonary lymphadenopathy is a
hallmark sign of different benign and malignant diseases of the chest. Contrast
enhanced (CE) chest CT is a test frequently applied to examine thoracic lymph
node zones. We attempted to find out whether mediastinal, hilar, and peripheral
lymph nodes delineate equally in CE chest CT with reduced dose (CE-LDCT, about 1
mSv) when compared with accepted standard CE chest CT (CE-SDCT). MATERIALS AND
METHODS: In this ethics committee-approved, mono-institutional, retrospective (20
months) matched case-control study, two independent, blinded observers compared
measurable lymph node delineation (yes-no) in six different International
Association for the Study of Lung Cancer (IASLC) zones (upper mediastinal,
aortopulmonary, subcarinal, lower mediastinal, hilar, peripheral) between 62 CE
LDCT cases and 124 CE-SDCT controls (respective tube charge, 100, 120 KVp,
computed tomography dose index, 1.66 +/- 0.51, 5.36 +/- 2.24 mGy, automatic
exposure control-modulated 64-row multi-detector chest CT with iterative image
reconstruction). Individual matching for gender (53% female), age (53 +/- 19
years), body height, weight, anterior-posterior and transverse diameters of chest
and lung ruled out pre-test confounders. Lymph node size (cut-off value, 1 cm)
was a potential post-test confounder. Two-tailed T test and Chi-square test were
significant for p < 0.05. RESULTS: Measurable lymph nodes delineated equally in
cases (261/372 IASLC zones, 70%; 280/372, 75%) and controls (528/744, 71%;
519/744, 70%; no significant differences, power 90%). One observer delineated
significantly more peripheral zone lymph nodes in cases (35/62) than in controls
(43/124); there were no significant differences otherwise. Lymph node size did
not differ significantly; effective dose was 1.0 +/- 0.3 mSv in cases and 3.4 +/-
1.5 mSv in controls. CONCLUSION: CE-LDCT with about 1 mSv demonstrated equal
delineation of thoracic lymph nodes when compared with accepted standard CE-SDCT.
PMID- 29961229
TI - Fast non-enhanced abdominal examination protocols in PET/MRI for patients with
neuroendocrine tumors (NET): comparison to multiphase contrast-enhanced PET/CT.
AB - PURPOSE: To evaluate fast non-enhanced protocols for abdominal PET/MRI in
comparison to contrast-enhanced PET/CT with somatostatin receptor (SSR)-specific
radiotracers regarding effectiveness of lesion detection in NET patients.
METHODS: This was a retrospective analysis of 29 patients (12 male, 57 +/- 13
years) who underwent PET/CT and subsequently PET/MRI at the same day. Two readers
evaluated independently four PET/MRI setups: (I) PET + T2 Half Fourier
Acquisition Single Shot Turbo Spin Echo (T2 HASTE), (II) PET + T2 HASTE + T2
weighted spin-echo sequence (T2 TSE), III) PET + T2 HASTE + Diffusion Weighted
Imaging (DWI) and (IV) PET + T2 HASTE + T2 TSE + DWI. A consensus reading of
PET/MRI and PET/CT including follow-up examinations served as the reference
standard for lesion-based analysis. Lesion sizes were assessed. RESULTS: Setup IV
provided comparable overall detection rates as PET/CT in both readers: PET/MRI
91.5%/92.9% versus 89.7% in PET/CT. In liver and bone lesions (mean diameter: 1.9
and 1.5 cm), PET/MRI was equal or superior to PET/CT: 98%/98% versus 85% in
PET/CT; 100%/95% versus 100% in PET/CT, but inferior in pancreatic lesions, small
bowel lesions and lymph node metastases (mean diameter: 1.3, 0.5 and 1.8 cm).
CONCLUSION: A non-enhanced MR protocol comprising T2 HASTE, T2 TSE and DWI for
SSR-PET/MRI seems to provide comparable effectiveness in lesions detection as
multiphase contrast-enhanced PET/CT. It might, therefore, serve as valid
alternative, e.g., for follow-up examinations in patients with unresectable NET
and kidney failure.
PMID- 29961230
TI - When Fathers are Perceived to Share in the Maternal Decision to Breastfeed:
Outcomes from the Infant Feeding Practices Study II.
AB - Objectives The present study investigates the influence of joint feeding
preferences of both the mother and father on initiation and duration of
breastfeeding. Methods Data from the Infant Feeding Practices Study II was
analyzed. Female participants in a national consumer opinion panel were followed
from pregnancy through 1 year postpartum, and were asked about infant feeding
practices. We examined the association between maternal prenatal perception of
the expectant father's breastfeeding preferences and breastfeeding outcomes
(initiation, duration of exclusive breastfeeding and any breastfeeding) and
whether concordance between the parents' infant feeding preferences influenced
breastfeeding. Results Mothers who perceived that the father preferred exclusive
breastfeeding (vs. no preference) were more likely to initiate breastfeeding
[adjusted odds ratio (aOR) = 1.9; 95% confidence interval (95% CI) 1.0-3.7], and
they had a lower hazard of stopping exclusive and any breastfeeding at any given
time [exclusive breastfeeding: adjusted hazard ratio (aHR) = 0.8; 95% CI 0.6-0.9;
any breastfeeding: aHR = 0.6; 95% CI 0.5-0.7]. When both the mother and the
father preferred exclusive breastfeeding, the hazard of breastfeeding cessation
at any given time was lowest (exclusive breastfeeding: aHR = 0.4; 95% CI 0.3-0.5;
any breastfeeding: aHR = 0.4; 95% CI 0.3-0.5). The risk of breastfeeding
cessation remained lower even when only the father preferred exclusive
breastfeeding. Conclusions for Practice Mothers tend to breastfeed for a longer
duration when they perceive that the expectant father prefers exclusive
breastfeeding and, even more so, when both parental preferences for exclusive
breastfeeding concur. Efforts are needed to involve expectant fathers in
breastfeeding decision-making and education to achieve breastfeeding success.
PMID- 29961231
TI - Breathing valve resistance alters physiological responses during a graded
exercise test.
AB - PURPOSE: To determine the impact of breathing valve resistance on peak aerobic
capacity ([Formula: see text]) and running economy (RE) in endurance-trained and
recreationally active individuals. METHODS: Ten endurance-trained males (ETM), 10
endurance-trained females (ETF), 10 recreationally active males (RAM), and 10
recreationally active females (RAF) participated in this study. On two separate
occasions, subjects performed identical graded exercise treadmill protocols using
either a Hans Rudolph 2700 (high resistance) or a Daniels' (low resistance) two
way non-rebreathing valve. Parameters obtained from these protocols included
energy expenditure (EE), ventilation ([Formula: see text]), heart rate,
respiratory exchange ratio, RE, [Formula: see text], and time to exhaustion
(TTE). RESULTS: When using the Daniels' valve, all groups had lower submaximal EE
(- 2.4, - 3.4, - 2.7, and - 2.0% for ETM, ETF, RAM, and RAF) and better RE (-
2.7, - 3.5, - 1.9, and - 1.8% for ETM, ETF, RAM and RAF) across all submaximal
speeds. Only the ET groups had lower submaximal [Formula: see text] (4.6 and 3.8%
for ETM and ETF) when using the Daniels' valve. TTE increased when using the
Daniels' valve for all groups (6.0, 10.9, 6.2 and 9.8% for ETM, ETF, RAM and
RAF), but [Formula: see text] was unaltered. CONCLUSION: Compared to the Daniels'
valve, the Hans Rudolph 2700 valve altered the assessment of RE, submaximal EE,
and TTE regardless of fitness level or sex, but did not change [Formula: see
text]. Therefore, airflow resistance of a breathing valve must be considered when
assessing and comparing EE, RE and TTE in the applied and research settings.
PMID- 29961232
TI - Neohesperidin Prevents Abeta25-35-Induced Apoptosis in Primary Cultured
Hippocampal Neurons by Blocking the S-Nitrosylation of Protein-Disulphide
Isomerase.
AB - A growing body of literature has established a link between the cerebral
ischaemic injury and pathological state of Alzheimer's disease (AD), and this
correlation indicated that the preventive agent for ischaemia might improve the
pathology of AD. Our previous studies have demonstrated that Neohesperidin (NH)
exhibited neuroprotective effects against cerebral ischemia via the down
regulation of Bcl-2, Akt/PI3K and Nrf2 pathways. In the present study, we first
confirmed the protective effects of NH on Abeta25-35-induced neurotoxicity on
primary cultured hippocampal neurons. We further demonstrated NH attenuated
Abeta25-35-induced apoptosis by preventing neurotoxicity associated with lethal
UPR and ER stress via blocking S-nitrosylation of protein-disulphide isomerase
(PDI). These results suggested that S-nitrosylation of PDI and ER dysfunction
might be the synergistic and synchronous pathological process between cerebral
ischaemia and AD.
PMID- 29961233
TI - Surgical strategy in extensive proximal brachial plexus palsies.
AB - PURPOSE: To describe and assess an overall surgical strategy addressing extensive
proximal brachial plexus injuries (BPI). METHODS: Forty-five consecutive
patients' charts with C5-C6-C7 and C5-C6-C7-C8 BPI were reviewed. Primary
procedures were nerve transfers to restore elbow function and grafts to restore
shoulder function when a cervical root was available; when nerve surgery was not
possible or had failed, tendon transfers were conducted at the elbow while
addressing shoulder function with glenohumeral arthrodesis or humeral osteotomy.
Tendon transfers were used to restore finger extension. RESULTS: Forty-one
patients underwent elbow flexion reanimation: thirty-eight had nerve transfers
and eight received tendon transfers, including five cases secondary to nerve
surgery failure; grade-3 strength or greater was reached in thirty-seven cases
(90%). Twenty-nine patients had nerve transfers to restore elbow extension:
twenty-five recovered grade-3 or grade-4 strength (86%). Forty-one patients
underwent shoulder surgery: fourteen had nerve surgery and thirty-one received
palliative procedures, including four cases secondary to nerve surgery failure;
thirty patients recovered at least 60 degrees of abduction and rotation (73%).
Distal reconstruction was performed in thirty-seven patients, providing finger
full extension in all cases but two (95%). CONCLUSIONS: A standardized strategy
may be used in extensive proximal BPI, providing overall satisfactory outcomes.
PMID- 29961235
TI - Novel biallelic PCNT deletion causing microcephalic osteodysplastic primordial
dwarfism type II with congenital heart defect.
PMID- 29961234
TI - The incidence, prevalence, and survival of systemic sclerosis in the UK Clinical
Practice Research Datalink.
AB - To estimate the incidence, prevalence, and survival of systemic sclerosis in the
United Kingdom. We conducted a historical cohort study using data from the
Clinical Practice Research Datalink (CPRD). We calculated the incidence and
survival of systemic sclerosis between 1994 and 2013 and examined its association
with age, sex, and socioeconomic status. We calculated point prevalence on 1 July
2013 and examined its association with the same exposures. We identified 1327
cases with incident systemic sclerosis. Annual incidence was 19.4 per million
person-years between 1994 and 2013. The incidence was 4.7 times higher in women
than in men, was not influenced by socioeconomic status, and has remained stable
over the 20 year study period. The peak age of onset was 55-69 years. Survival at
1, 5, and 10 years was 94.2, 80.0, and 65.7%, respectively. The prevalence was
307 (290-323) per million with the highest prevalence in the 70-84 years age
group. We estimate there are currently 1180 new cases of systemic sclerosis each
year in the UK, and 19,390 people living with systemic sclerosis. Due to the
predicted growth and aging of the population, we predict a 24% increase in
incident cases and 26% increase in prevalent cases in 20 years' time. Our
estimates of incidence and prevalence are higher than previously reported in the
UK, but similar to recent USA and Swedish studies, and do not support a north
south gradient of the occurrence of systemic sclerosis in Europe.
PMID- 29961236
TI - Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver
fibrosis model.
AB - Biomarker is the change associated with the disease. Blood is relatively stable
because of the homeostatic mechanisms of the body. However, urine accumulates
changes of the body, which makes it a better early biomarker source. Liver
fibrosis is a reversible pathological condition, whereas cirrhosis, the end-stage
of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers
for fibrosis are desperately needed. In this study, differential urinary proteins
were identified in the thioacetamide liver fibrosis rat model using tandem mass
tagging and two-dimensional liquid chromatography tandem mass spectrometry. A
total of 766 urinary proteins were identified, 143 and 118 of which were
significantly changed in the TAA 1-week and 3-week groups, respectively. Multiple
reaction monitoring (MRM)-targeted proteomics was used to further validate the
abundant differentially expressed proteins. A total of 40 urinary proteins were
statistically significant, 15 of which had been previously reported as biomarkers
of liver fibrosis, cirrhosis or other related diseases and 10 of which had been
reported to be associated with the pathology and mechanism of liver fibrosis.
These differential proteins were detected in urine before the alanine
aminotransferase and aspartate transaminase changes in the serum and before
fibrosis was observed upon hematoxylin and eosin (HE) and Masson's staining.
PMID- 29961237
TI - Efficiency of structural connectivity networks relates to intrinsic motivation in
children born extremely preterm.
AB - Intrinsic motivation is essential for academic success and cognitive growth, but
limited work has examined the neuroanatomical underpinnings of intrinsic
motivation from a network perspective, particularly in early childhood. Using
graph theoretical analysis, this study investigated global and local properties
of structural connectivity networks in relation to intrinsic motivation within a
vulnerable group of children at early school age. Fifty-three 7 year-old children
born extremely preterm (<28 weeks' gestational age)/extremely low birth weight
(<1000 g) underwent T1 and diffusion weighted imaging. Structural connectivity
networks were generated using 162 cortical and subcortical nodes, and edges were
created using constrained spherical deconvolution-based tractography. Global and
node-specific network measures were analyzed in association with self-reported
aspects of intrinsic motivation for school learning (Mastery, Challenge and
Curiosity) using linear regression. Results indicated that increased information
transfer across the network was associated with greater Mastery, while increased
clustering and small-world topology related to greater Challenge. Increased
efficiency and connection strength of the striatum in particular, related to
greater intrinsic motivation. These findings suggest that both integrated and
segregated network communication support aspects of intrinsic motivation in
childhood, and shed new light on structural network properties important for
intrinsic motivation orientations in extremely preterm children at early school
age.
PMID- 29961238
TI - Axillary reverse mapping (ARM): where to go.
AB - In the past decades, breast surgeons have changed the clinical practice in the
surgical treatment of breast cancer, by performing sentinel lymph node biopsy
(SLNB) instead of performing axillary lymph node dissection (ALND) in axillary
lymph node clinically negative breast cancer patients. ALND can also be avoided
in SLN-positive patients who meet the Z-0011 criteria. However, the postoperative
complications of SLNB and ALND, such as the secondary upper extremity lymphedema,
are common and need effective solutions to prevent as soon as possible. The
axillary reverse mapping (ARM) technique has been developed to map and preserve
arm lymphatic drainage during ALND and/or SLNB, thereby minimizing arm
lymphedema. However, the success of ARM in reducing lymphedema has not been
exactly determined. If ARM can be confirmed to be both effective and
oncologically safe in preventing lymphedema, this technique should be recommended
in the management of breast cancer treatment.
PMID- 29961239
TI - Physiological determinants of walking effort in older adults: should they be
targets for physical activity intervention?
AB - Older adults do not get enough physical activity increasing risk for chronic
disease and loss of physical function. The purpose of this study was to determine
whether neuromuscular, metabolic, and cardiorespiratory indicators of walking
effort explain daily activity in community-dwelling older adults. Sixteen women
and fourteen men, 78 +/- 8 years, performed a steady-state walk on a treadmill at
1.25 m s-1 while muscle activation, heart rate, lactate, respiratory exchange
ratio, oxygen consumption (VO2), ventilation, and rating of perceived exertion
(RPE) were recorded as markers of Walking Effort. Daily walking time,
sitting/lying time, energy expenditure, and up-down transitions were recorded by
accelerometers as markers of Daily Activity. Structural equation modeling was
used to explore the relationship between the latent variables Walking Effort and
Daily Activity controlling for age and BMI. Participants spent 9.4 +/- 1.9 h of
the waking day sedentary and 1.9 +/- 0.6 h walking. In the structural equation
model, the latent variable Walking Effort explained 64% of the variance in the
Daily Activity latent variable (beta = 0.80, p = 0.004). Walking Effort was
identified by heart rate (beta = 0.64), ventilation (beta = 0.88), vastus
lateralis activation (beta = 0.49), and lactate (beta = 0.58), all p < 0.05, but
not RPE or VO2. Daily Activity was identified by stepping time (beta = 0.75) and
up-down transitions (beta = 0.52), all p < 0.05. Walking effort mediated the
effects of age and BMI on older adults' daily activity making physiological
determinants of walking effort potential points of intervention.
PMID- 29961240
TI - Experiencing and Learning About Emotions: A Longitudinal Analysis of Youth
Program Participants.
AB - Organized youth programs provide a context where adolescents experience strong
emotions and may develop new ways of thinking about and dealing with emotions.
The current study examined youth's reports of positive and negative emotions
arising during the course of their work in different types of project-based
programs; learning about emotions from different sources (e.g., from observing
peers, interacting with adult staff, or engaging in self-reflection); and
longitudinal associations between emotional experiences and learning.
Quantitative data were collected at two time points from 319 youth (57% female; M
age = 15.8 years; 33% Latino, 29% Black, 32% White, 6% other) participating in 14
Midwestern programs focused on Leadership, Arts and Performance (Arts), and
Science, Technology, Engineering, and Math (STEM). Overall, positive emotions
occurred more frequently than negative emotions, but emotional experiences
differed based on the focus of the program. There were few significant
differences in emotional learning from various sources (self, peers, staff)
across the three types of programs. Multiple regression models controlling for
prior learning indicated that, consistent with theory, positive emotions
predicted subsequent learning about emotions from all sources. In contrast,
negative emotions predicted increased learning from peers but decreased learning
from self, suggesting that experiencing negative (vs. positive) emotions may lead
youth to attend to different sources of information. The study's findings have
implications for theory, research, and practice.
PMID- 29961241
TI - The Temporal Dynamics of Neighborhood Disadvantage in Childhood and Subsequent
Problem Behavior in Adolescence.
AB - Research on neighborhood effects has increasingly focused on how long children
have lived in a deprived neighborhood during childhood (duration), but has
typically ignored when in childhood the exposure occurred (timing) and whether
neighborhood circumstances were improving or deteriorating (sequencing). In this
article, the authors applied sequence analysis to simultaneously capture
children's duration, timing, and sequencing of exposure to neighborhood
(dis)advantage in childhood. Logistic regression analysis was subsequently used
to test how different patterns of exposure are related to teenage parenthood,
school dropout, and delinquent behavior. Using register data from the
Netherlands, an entire cohort was followed from birth in 1995 up until age 19 in
2014 (N = 168,645, 48.8% females, 83.2% native Dutch). Compared to children who
had lived in a deprived neighborhood throughout childhood, children who were
exposed to neighborhood deprivation only during adolescence were found to be
equally likely to become a teenage parent and were even more likely to drop out
of school. Unexpectedly, children who had lived in an affluent neighborhood
throughout childhood were most likely to engage in delinquent behavior. Possible
explanations and implications are discussed.
PMID- 29961243
TI - Recurrent hepatic failure and status epilepticus: an uncommon presentation of
hyperargininemia.
AB - Argininemia is a rare hereditary disease due to a deficiency of hepatic arginase,
which is the last enzyme of the urea cycle and hydrolyzes arginine to ornithine
and urea. Herein we report a patient with arginase I (ARG1) deficiency who
presented with recurrent nonconvulsive status epilepticus and liver failure. A
novel homozygous frameshift mutation c.703_707delGGACTinsAGACTGGACC
(p.G235Rfs*20) was detected.
PMID- 29961244
TI - Turkish Insulin Injection Techniques Study: Complications of Injecting Insulin
Among Turkish Patients with Diabetes, Education They Received, and the Role of
Health Care Professional as Assessed by Survey Questionnaire.
AB - INTRODUCTION: Using the Turkish and rest of world (ROW) Injection Technique
Questionnaire (ITQ) data we address key insulin injection complications. METHODS:
Summarized in first ITQ paper. RESULTS: Nearly one-third of Turkish insulin users
described lesions consistent with lipohypertrophy (LH) at their injection sites
and 27.4% were found to have LH by the examining nurse (using visual inspection
and palpation). LH lesions in the abdomen and thigh of Turkish patients are
slightly smaller than those measured in ROW but more than half of Turkish
patients who have LH continue to inject into them at least daily. More than a
quarter of Turkish patients have frequent unexplained hypoglycemia and nearly 2
out of 5 have glycemic variability, both of which have been linked to the
presence of LH and the habit of injecting into it. Nearly half of Turkish
injectors report having pain on injection. Of these, just over half report having
painful injections only several times a month or year (i.e., not with every
injection). In Turkey the diabetes nurse has by far the major role in teaching
patients how to inject. Nearly 40% of Turkish injectors get their sites checked
at least annually, and a larger proportion than ROW had received recent (within
the last 12 months) instruction on how to inject properly. CONCLUSION: Turkish
patients and professionals have clearly made progress in injection technique, but
there are still considerable challenges ahead which the new Turkish guidelines
will help address. FUNDING: BD Diabetes Care.
PMID- 29961245
TI - Turkish Insulin Injection Technique Study: Population Characteristics of Turkish
Patients with Diabetes Who Inject Insulin and Details of Their Injection
Practices as Assessed by Survey Questionnaire.
AB - INTRODUCTION: Over 7 million people in Turkey have diabetes. Of the 1 million who
inject insulin little is known of their habits and injection techniques. METHODS:
We conducted an Injection Technique Questionnaire (ITQ) survey throughout Turkey
that involved 1376 patients from 56 centers. Turkish values were compared with
those from 41 other countries participating in the ITQ, known here as Rest of
World (ROW). RESULTS: The majority (50.4%) of Turkish insulin users give four
injections/ day as opposed to ROW, where only 30.9% do. The abdomen is the most
common injection site used by Turkish patients, but they also inject insulin in
multiple body sites more often than do patients in ROW. Body mass index values in
Turkey were 0.75 units higher than those in ROW as was the mean total daily dose
(average daily dose [ADD]) of insulin (54.0 IU in Turkey vs. 47.4 IU in ROW).
Mean glycated hemoglobin (HbA1c) in Turkey was 9.1%, which is higher than in ROW
and possibly related to the higher BMI and ADD. Turkish patients use insulin
analogs (short and long-acting) more frequently than do patients in ROW. The
shortest pen needles (4 mm) are used by about one-third of patients in Turkey,
but the longer ones (8 mm) are equally common. Needles are reused in Turkey at a
rate of 3.4 injections/single needle. However, needle reuse, whether with pens or
syringes, is lower in Turkey than ROW, as is the number of times a reused needle
is used. More than 75% of used sharps in Turkey go into the rubbish, with nearly
6% having no protection of the tip. CONCLUSION: The continued use of 8-mm needles
raises the risk of intramuscular injections in Turkish patients. Despite full
reimbursement, needle reuse still remains an important issue. More focus needs to
be given to dwell times under the skin, reconstitution of cloudy insulant,
correct use of skin folds and safe disposal of sharps. FUNDING: BD Diabetes Care.
PMID- 29961246
TI - Glycemic Control in Hospitalized Patients with Diabetes Receiving Corticosteroids
Using a Neutral Protamine Hagedorn Insulin Protocol: A Randomized Clinical Trial.
AB - INTRODUCTION: Hospitalized patients with diabetes receiving corticosteroids are
at risk of developing hyperglycemia and related complications. This study
evaluated a neutral protamine Hagedorn (NPH) insulin-based protocol in improving
glycemic control in hospitalized patients receiving corticosteroids. METHODS:
This was a randomized, prospective, non-blinded study in an inpatient setting
involving patients with diabetes who were hospitalized and receiving prednisone
>= 10 mg per day or equivalent. High dose corticosteroids group (prednisone > 40
mg/day or equivalent) received NPH insulin 0.3 U/kg between 0600 and 2000 hours
if eating or 0.2 U/kg between 2000 and 0600 hours if not eating. Low dose
corticosteroids group (prednisone 10-40 mg/day or equivalent) received 0.15 U/kg
between 0600 and 2000 hours if eating or 0.1 U/kg between 2000 and 0600 hours if
not eating. Primary outcome measure was mean blood glucose level measured pre
meal and at bedtime for days 1-5. RESULTS: Mean blood glucose level was lower in
the intervention (n = 29) than in the usual care (n = 31) group [226.12 vs.
268.57 mg/dL, respectively, (95% CI for difference - 63.195 to - 21.695), p <
0.0001]. Significant differences in mean glucose level were noted at fasting
[170.96 vs. 221.13 mg/dL, respectively, (95% CI for difference - 72.70 to -
27.63), p < 0.0001] and pre-lunch [208 vs. 266.48 mg/dL, respectively, (95% CI
for difference - 86.61 to - 30.36), p < 0.0001]. CONCLUSION: In hospitalized
patients with diabetes receiving corticosteroids, an NPH insulin-based protocol
improves glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
NCT01970241. FUNDING: Eli Lilly and Company.
PMID- 29961248
TI - Grammatical Aspect in Early Child Mandarin: Evidence from a Preferential Looking
Experiment.
AB - The study assessed 30-month-old Mandarin-speaking children's awareness of
aspectual distinctions involving the perfective marker le and the imperfective
marker zhe in a preferential looking experiment. In the experiment, we presented
our child subjects with a choice between two video clips (one depicting a closed
event and the other depicting an on-going event), in the presence of an auditory
stimulus (either the le sentence, the zhe sentence or the control sentence
without any aspect marker). Children's looking behavior in the task was recorded
and analyzed. The results revealed 30-month-old children's emerging sensitivity
to the aspectual contrast between le and zhe. This was manifest by an increase in
looking to the closed event when hearing the le sentence and an increase in
looking to the on-going event when hearing the zhe sentence. The absence of le or
zhe in the control sentence did not result in any increase or decrease in looking
to either event. We also found that the effect of le on children's looking
behavior was immediate whereas the effect of zhe was late. We attributed this
difference to the facilitative role of le in children's sentence processing as
well as their preference for the event boundary. The results lend support to the
continuity view that functional morphemes like aspect markers are available to
children early in language development.
PMID- 29961249
TI - Growth In Vitro of Granulosa Cell-Oocyte Complexes of the Mouse.
AB - Analysis of the mechanisms that drive the growth and meiotic maturation of the
female germ cell, the oocyte, has been greatly facilitated by the development of
conditions that support these processes in vitro. Easily identified signposts of
oocyte differentiation enable the ability of specific culture conditions to
recapitulate normal oocyte development to be robustly assayed. Here we describe a
technique for deriving complexes consisting of an oocyte surrounded by somatic
granulosa cells from follicles and growing these granulosa cell-oocyte complexes
in vitro. Such culture systems are useful for uncovering the principles of germ
cell development and for improving our ability to preserve human and animal
fertility through assisted reproduction.
PMID- 29961247
TI - The Role of Testosterone Therapy in the Setting of Prostate Cancer.
AB - PURPOSE OF REVIEW: The role of testosterone in the development of prostate cancer
and the safety of testosterone therapy (TTh) after prostate cancer treatment, or
in the setting of active surveillance, remains controversial. There are many
concerns about using TTh in men, particularly those with a history of prostate
cancer, ranging from a possible increased risk of cardiovascular disease to
cancer progression or recurrence. With many prostate cancer patients living
longer, and hypogonadism having significant morbidity, much care must go into the
decision to treat. Here, we review the literature investigating the effects of
testosterone on the prostate as well as the efficacy and safety of exogenous
testosterone in men with a history of prostate cancer. RECENT FINDINGS: The
improvement in quality of life with TTh is well studied and understood, while the
argument for significantly increased risk of cancer or other adverse effects is
much less robust. Neither increased rates of prostate cancer, cancer recurrence,
or cardiovascular risk have been well established. In men with high-risk prostate
cancer, evidence in the setting of TTh is very limited, and TTh should be used
with caution. The fears of TTh causing or worsening prostate cancer do not appear
to be well supported by available data. Though more studies are needed to
definitively determine the safety of TTh in men with prostate cancer,
consideration should be given to treatment of hypogonadal men with a history of
CaP.
PMID- 29961250
TI - In Vitro Culture of Mouse Oocytes for Meiotic Maturation.
AB - In vitro maturation of mouse oocytes, as well as of many other mammalian species,
is used commonly in experimental embryology. This model system gives the
possibility to easily obtain maturing oocytes at desired stages of the maturation
process. Here we describe how to establish the in vitro culture of maturating
mouse oocytes. We focus on the use of oocytes maturation inhibitors to
synchronize oocytes at the GVBD stage and on the procedure to distinguish between
transcribing and nontranscribing GV-arrested oocytes.
PMID- 29961251
TI - In Vitro Maturation and Culture of Human Oocytes.
AB - We describe the collection, culture, and ex vivo, in vitro maturation of germinal
vesicle (GV) oocytes obtained from human small antral follicles (hSAFs). hSAFs
contain fully grown GV oocytes and have the advantages that they are more
numerous than large or mature follicles, which are used in IVF treatment. hSAFs
can be obtained directly from human ovarian tissue without exogenous
gonadotrophin stimulation and therefore allows studies of oocytes even from young
women and girls. The method described here was developed to study human female
meiosis but could in theory also be used for fertility treatment.
PMID- 29961252
TI - Pronuclear Transfer in Human Oocytes.
AB - The method described is for early pronuclear transfer (PNT) in normally
fertilized human eggs. The PNT procedure should be performed shortly after the
appearance of the two pronuclei. Each pronucleus is pinched off with a minimal
amount of surrounding cytoplasm to form a membrane enclosed karyoplast. The
karyoplasts are then fused with a fertilized egg which has had its pronuclei
removed. An experienced individual will achieve approximately 90% survival of the
fertilized eggs manipulated.
PMID- 29961253
TI - In Vitro Fertilization of Mouse Oocyte.
AB - The early development of embryos is a widely studied process. Fertilization is
the consequence of the fusion of two haploid gametes, the oocyte and the sperm.
In mammals, such as human and mouse, this occurs in the female genital tracks.
However, imaging in utero is still very limited, which prompts the use of extra
utero techniques. In particular, in vitro fertilization provides a quick and
simple way to study the very early steps of mouse embryo development. Here, I
describe a simple and hands-on protocol to perform in vitro fertilization using
the mouse as a model system.
PMID- 29961254
TI - Profiling Maternal mRNA Translation During Oocyte Development.
AB - With the progress in our understanding of germ cell development, there is an
emerging need to investigate the mechanisms of mRNA translation functioning in
these cells. Indeed, posttranscriptional regulations of gene expression drive the
most important transitions of the germ cell life cycle. Here we describe a
strategy to measure mRNA translation in the oocyte, taking advantage of an
approach originally developed to identify the transcriptome of a subgroup of
cells in a complex cell mixture. This technique takes advantage of the "RiboTag"
approach to express an HA-tag on the large ribosomal subunit of the ribosomes in
the oocyte. Immunoprecipitation of the extracts followed by qPCR or RNAseq is
used to identify mRNAs actively translated.
PMID- 29961255
TI - Transcriptome Profiling of Single Mouse Oocytes.
AB - Single-cell RNA-sequencing (scRNAseq) enables the detection and quantification of
mature RNAs in an individual cell. Assessing single cell transcriptomes can
circumvent the limited amount of starting material obtained in oocytes or
embryos, in particular when working with mutant mice. Here we outline our
scRNAseq protocol to study mouse oocyte transcriptomes, derived from Tang et al.,
Nat Methods 6(5):377-382, 2009 . The method describes the different steps from
single cell isolation and cDNA amplification to high-throughput sequencing. The
bioinformatics pipeline used to analyze and compare genome-wide gene expression
between individual oocytes is then described.
PMID- 29961256
TI - Immunofluorescence Technique to Detect Subcellular Structures Critical to Oocyte
Maturation.
AB - Immunofluorescence is a useful technique for analysis of protein expression and
localization, thereby providing information regarding protein function,
regulation, and protein-protein interactions. It is a standard approach to
determine the temporal and spatial location of gene products that function in
oocyte meiotic maturation. Fixation is one of the critical steps in the
immunofluorescence protocol. Here, we describe the use of antibodies that are
widely utilized in oocytes studies: anti-centromeric antigen (ACA), anti-Aurora
kinase A (AURKA) and anti-alpha and gamma-tubulin antibodies that require
different technical approaches for successful visualization, and we provide
protocols for these conditions that are amenable to mouse oocyte studies.
Detection of these proteins provides phenotypic information about spindle
morphology, chromosome alignment, and microtubule attachments to kinetochores
critical to assessing oocyte quality.
PMID- 29961257
TI - Immunofluorescence Staining of K-Fibers in Mouse Oocytes Using Cold Fixation.
AB - The kinetochore is a multiprotein complex that assembles on centromeric DNA and
constitutes the main attachment interface between chromosomes and microtubules of
the spindle apparatus. Kinetochores also provide the platform for integrating the
surveillance mechanism known as the spindle assembly checkpoint (SAC) that
regulates the timing of anaphase onset. Saturation of microtubule binding sites
on kinetochores displaces SAC proteins leading to loss of SAC-mediated inhibition
and the triggering of anaphase. Microtubule binding sites become saturated by
bundles of microtubules attached in an end-on manner to kinetochores, termed
kinetochore fibers or K-fibers. The appearance of K-fibers therefore signifies
the completion of attachment between kinetochores and microtubules and the
silencing of the SAC. Here we describe a method involving cold-fixation for
immunostaining and imaging K-fibers during meiosis I in mouse oocytes.
PMID- 29961258
TI - Triple-Color Live Imaging of Mouse Oocytes.
AB - Meiotic division is a dynamic process that exhibits active interactive behaviors
amongst different intracellular structures and components for spindle assembly
and chromosome segregation. Understanding the mechanisms of meiotic spindle
assembly and chromosome segregation therefore requires a quantitative analysis of
spatiotemporal relationships among different structures and components. In this
chapter, we describe a method for triple-color live imaging of meiotic division
in mouse oocytes. This approach combines the microinjection of RNAs encoding
proteins tagged with green and red fluorescent proteins and the visualization of
microtubules with the fluorogenic far-red probe SiR-Tubulin. This method enables
the simultaneous spatiotemporal mapping of three different components of the
spindle and chromosomes, which opens the way to quantitative analysis of their
interactive behaviors.
PMID- 29961259
TI - Detection of Separase Activity Using a Cleavage Sensor in Live Mouse Oocytes.
AB - Separase proteolytically removes cohesin complexes from sister chromatid arms in
meiosis I, which is essential for chromosome segregation. Regulation of separase
activity is essential for proper cell cycle progression and correct chromosome
segregation. Onset of endogenous separase activity has not yet been observed in
live oocytes.We describe here a method for detecting separase activity in mouse
oocytes in vivo. This method utilizes a previously described cleavage sensor made
up of H2B-mCherry fused with Scc1(107-268 aa)-YFP. The cleavage sensor is loaded
on the chromosomes through its H2B-tag, and the signal from both mCherry and YFP
is visible. Upon separase activation the Scc1 fragment is cleaved and YFP
dissociates from the chromosomes. The change in the ratio between mCherry and YFP
fluorescence intensity is a readout of separase activity.
PMID- 29961260
TI - Manipulating Cohesin Levels in Live Mouse Oocytes.
AB - The cohesin complex is essential for chromosome segregation in mitosis and
meiosis. Cohesin is a tripartite protein complex that holds sister chromatids
together from DNA replication until anaphase. In mammals, meiotic DNA replication
occurs in oogonia of embryos and chromosome segregation occurs in oocytes of
sexually mature females. Sister chromatid cohesion establishment and chromosome
segregation are thus separated by months in the mouse and decades in the human.
The meiotic cohesin complex that maintains sister chromatid cohesion must
therefore hold replicated sisters together for a long time in oocytes.
Remarkably, this is achieved by establishing cohesion exclusively in prenatal
oocytes. Meiotic cohesion in females is maintained without detectable turnover
and cohesin is therefore thought to be a long-lived protein complex.
Nevertheless, the lifespan of cohesin molecules is limited as chromosomal cohesin
levels decline with maternal age. The age-related loss of cohesin and weakened
cohesion correlate with an age-related increase in chromosome missegregation of
meiosis I oocytes that results in aneuploid eggs. Therefore, loss of chromosomal
cohesin has been proposed to be a leading cause of the maternal age effect. To
better understand cohesin deterioration in oocytes, it is crucial to gain
insights into mammalian cohesion establishment and maintenance mechanisms by
manipulating cohesin in live oocytes.This chapter describes techniques that
address the manipulation of meiotic cohesin levels in mouse oocytes. First, we
describe how cohesin can be efficiently removed from meiotic chromosomes by
injecting mRNA encoding TEV protease in live oocytes expressing cohesin with
engineered TEV recognition sites, followed by imaging. Secondly, we describe how
cohesin expression can be induced during different stages of oocyte development
using genetically modified mouse strains. In particular, we describe how to
determine the deletion timing of germline-specific Cre recombinases using beta
galactosidase staining of fetal ovaries. Lastly, we provide guidance on how to
quantify cohesin levels on metaphase I chromosome spreads.
PMID- 29961261
TI - Optogenetic Manipulation of Mouse Oocytes.
AB - Like many biological processes, oocyte development depends on careful
orchestration of protein localization. Optogenetic approaches have the potential
to manipulate this dynamic system with spatial and temporal precision and
molecular specificity. This chapter describes the use of a photocaged chemical
inducer of dimerization to control localization of genetically tagged proteins
with light. As an example, we recruit a fluorescently tagged protein to one
spindle pole in metaphase.
PMID- 29961262
TI - Monitoring Microtubule Dynamics in the Mouse Egg Using Photoactivatable-GFP
Tubulin.
AB - Fluorescence photoactivation provides a strategy for monitoring protein kinetics
within living cells. In particular, fluorescence photoactivation of a
subpopulation of microtubule subunits within the spindle using photoactivatable
fluorescent tubulin constructs has proven useful for assessing a variety of
features of spindle microtubule dynamics, including poleward microtubule
movement, microtubule depolymerization, and microtubule turnover, in various
cellular settings. The current chapter describes a method for monitoring
microtubule dynamics within the mouse egg spindle by photoactivation of
photoactivatable-GFP-tubulin, followed by time-lapse confocal imaging.
PMID- 29961263
TI - Photoactivation of Actin in Mouse Oocyte.
AB - Development of fluorescence distribution assays like FRAP (fluorescence recovery
after photobleaching) or photoactivation has had a great impact in studying
intracellular protein dynamics. In particular, the cytoskeleton field largely
benefited from these techniques, with lots of new information provided about the
dynamics and organization of actin networks whithin cells.In mouse oocyte, actin
photoactivation has been very useful to determine the dynamics of different actin
structures involved in meiotic divisions, including a cytoplasmic meshwork and a
subcortical actin layer.Here, we describe a method, actin photoactivation, to
determine the dynamics of the actin cytoplasmic meshwork and the subcortical
actin layer during the first meiotic division in the mouse oocyte, that could be
adapted to other actin structures or other stages of meiotic divisions.
PMID- 29961264
TI - Laser Ablation of Microtubule-Chromosome Attachment in Mouse Oocytes.
AB - Laser ablation is a powerful tool to study forces within biological systems. This
technique has been extensively used to study mitotic spindle formation and
chromosome segregation. This chapter describes laser ablation of microtubule
chromosome attachments coupled to fluorescence live microscopy and quantitative
analysis of individual chromosome movement after microtubule severing. This
method allows to gain insight into the organization and dynamics of the meiotic
spindle and chromosomes in metaphase I mouse oocytes.
PMID- 29961265
TI - Micropipette Aspiration of Oocytes to Assess Cortical Tension.
AB - Just as it is important to understand the cell biology of signaling pathways, it
is valuable also to understand mechanical forces in cells. The field of
mechanobiology has a rich history, including study of cellular mechanics during
mitosis and meiosis in echinoderm oocytes and zygotes dating back to the 1930s.
This chapter addresses the use of micropipette aspiration (MPA) to assess
cellular mechanics, specifically cortical tension, in mammalian oocytes.
PMID- 29961266
TI - Honesty Speaks a Second Language.
AB - Theories of dishonest behavior implicitly assume language independence. Here, we
investigated this assumption by comparing lying by people using a foreign
language versus their native tongue. Participants rolled a die and were paid
according to the outcome they reported. Because the outcome was private, they
could lie to inflate their profit without risk of repercussions. Participants
performed the task either in their native language or in a foreign language. With
native speakers of Hebrew, Korean, Spanish, and English, we discovered that, on
average, people inflate their earnings less when they use a foreign language. The
outcome is explained by a dual system account that suggests that self-serving
dishonesty is an automatic tendency, which is supported by a fast and intuitive
system. Because using a foreign language is less intuitive and automatic, it
might engage more deliberation and reduce the temptation to lie. These findings
challenge theories of ethical behavior to account for the role of the language in
shaping ethical behavior.
PMID- 29961268
TI - Shedding Light on Keeping People in the Dark.
AB - We want to keep hackers in the dark about our passwords and our credit card
numbers. We want to keep potential eavesdroppers in the dark about our private
communications with friends and business associates. This need for secrecy raises
important questions in epistemology (how do we do it?) and in ethics (should we
do it?). In order to answer these questions, it would be useful to have a good
understanding of the concept of keeping someone in the dark. Several philosophers
(e.g., Bok, 1983; Carson, 2010; Mahon, 2009; Scheppele, 1988) have analyzed this
concept (or, equivalently, the concept of keeping secrets) in terms of concealing
and/or withholding information. However, their analyses incorrectly exclude clear
instances of keeping someone in the dark. And more important, they incorrectly
focus on possible means of keeping someone in the dark rather than on what it is
to keep someone in the dark. In this paper, I argue that you keep X in the dark
about a proposition P if and only if you intentionally cause X not to have a true
belief that P. In addition, I show how this analysis of keeping someone in the
dark can be extended from a categorical belief model of epistemic states to a
credence (or degree of belief) model.
PMID- 29961267
TI - Differential patterns of age-related cortical and subcortical functional
connectivity in 6-to-10 year old children: A connectome-wide association study.
AB - INTRODUCTION: Typical brain development is characterized by specific patterns of
maturation of functional networks. Cortico-cortical connectivity generally
increases, whereas subcortico-cortical connections often decrease. Little is
known about connectivity changes amongst different subcortical regions in typical
development. METHODS: This study examined age- and gender-related differences in
functional connectivity between and within cortical and subcortical regions using
two different approaches. The participants included 411 six- to ten-year-old
typically developing children sampled from the population-based Generation R
study. Functional connectomes were defined in native space using regions of
interest from subject-specific FreeSurfer segmentations. Connections were defined
as: (a) the correlation between regional mean time-series; and (b) the focal
maximum of voxel-wise correlations within FreeSurfer regions. The association of
age and gender with each functional connection was determined using linear
regression. The preprocessing included the exclusion of children with excessive
head motion and scrubbing to reduce the influence of minor head motion during
scanning. RESULTS: Cortico-cortical associations echoed previous findings that
connectivity shifts from short to long-range with age. Subcortico-cortical
associations with age were primarily negative in the focal network approach but
were both positive and negative in the mean time-series network approach. Between
subcortical regions, age-related associations were negative in both network
approaches. Few connections had significant associations with gender.
CONCLUSIONS: The present study replicates previously reported age-related
patterns of connectivity in a relatively narrow age-range of children. In
addition, we extended these findings by demonstrating decreased connectivity
within the subcortex with increasing age. Lastly, we show the utility of a more
focal approach that challenges the spatial assumptions made by the traditional
mean time series approach.
PMID- 29961269
TI - Dysregulated circRNAs in plasma from active tuberculosis patients.
AB - Endogenous circular RNAs (circRNAs) have been reported in various diseases.
However, their role in active TB remains unknown. The study was aimed to
determine plasma circRNA expression profile to characterize potential biomarker
and improve our understanding of active TB pathogenesis. CircRNA expression
profiles were screened by circRNA microarrays in active TB plasma samples.
Dysregulated circRNAs were then verified by qRT-PCR. CircRNA targets were
predicted based on analysis of circRNA-miRNA-mRNA interaction. GO and KEGG
pathway analyses were used to predict the function of circRNA. ROC curve was
calculated to evaluate diagnostic value for active TB. A total of 75 circRNAs
were significantly dysregulated in active TB plasma. By further validation,
hsa_circRNA_103571 exhibited significant decrease in active TB patients and
showed potential interaction with active TB-related miRNAs such as miR-29a and
miR-16. Bioinformatics analysis revealed that hsa_circRNA_103571 was primarily
involved in ras signalling pathway, regulation of actin cytoskeleton, T- and B
cell receptor signalling pathway. ROC curve analysis suggested that
hsa_circRNA_103571 had significant value for active TB diagnosis. Circulating
circRNA dysregulation may play a role in active TB pathogenesis.
Hsa_circRNA_103571 may be served as a potential biomarker for active TB
diagnosis, and hsa_circRNA_103571-miRNA-mRNA interaction may provide some novel
mechanism for active TB.
PMID- 29961272
TI - Erratum.
PMID- 29961270
TI - Jaguar movement database: a GPS-based movement dataset of an apex predator in the
Neotropics.
AB - The field of movement ecology has rapidly grown during the last decade, with
important advancements in tracking devices and analytical tools that have
provided unprecedented insights into where, when, and why species move across a
landscape. Although there has been an increasing emphasis on making animal
movement data publicly available, there has also been a conspicuous dearth in the
availability of such data on large carnivores. Globally, large predators are of
conservation concern. However, due to their secretive behavior and low densities,
obtaining movement data on apex predators is expensive and logistically
challenging. Consequently, the relatively small sample sizes typical of large
carnivore movement studies may limit insights into the ecology and behavior of
these elusive predators. The aim of this initiative is to make available to the
conservation-scientific community a dataset of 134,690 locations of jaguars
(Panthera onca) collected from 117 individuals (54 males and 63 females) tracked
by GPS technology. Individual jaguars were monitored in five different range
countries representing a large portion of the species' distribution. This dataset
may be used to answer a variety of ecological questions including but not limited
to: improved models of connectivity from local to continental scales; the use of
natural or human-modified landscapes by jaguars; movement behavior of jaguars in
regions not represented in this dataset; intraspecific interactions; and predator
prey interactions. In making our dataset publicly available, we hope to motivate
other research groups to do the same in the near future. Specifically, we aim to
help inform a better understanding of jaguar movement ecology with applications
towards effective decision making and maximizing long-term conservation efforts
for this ecologically important species. There are no costs, copyright, or
proprietary restrictions associated with this data set. When using this data set,
please cite this article to recognize the effort involved in gathering and
collating the data and the willingness of the authors to make it publicly
available.
PMID- 29961271
TI - Are cortisol concentrations in human breast milk associated with infant crying?
AB - The present longitudinal study is the first to investigate the association
between human breast milk cortisol and infant crying over the first three months
of life. Higher concentrations of breast milk cortisol were expected to be
differentially associated with fussing and crying in boys and girls. At 2, 6, and
12 weeks of infant age, mothers (N = 70) collected a morning sample of their milk
and kept a 3-day diary to measure infant fussing and crying. Cortisol was
extracted and quantified from milk samples. Results showed that breast milk
cortisol concentrations increased from 2 weeks through 12 weeks of infant age.
Milk cortisol was unrelated to the total duration, frequency, and bout length of
infant fussing and crying for both boys and girls. Directions for future research
aiming to extend our knowledge on the biology of milk cortisol in relation to
infant behavior and development are discussed.
PMID- 29961274
TI - Application of Traditional Chinese Medicine in medical practice: a survey of
community residents in Beijing, China.
AB - OBJECTIVE: To investigate how community residents in Beijing understood and used
TraditionalChinese Medicine (TCM) in their medical practice. METHODS: This was a
cross-sectional study conducted on 3410 community residents from fourlarge
communities of Tongzhou district in Beijng, China. A validated, self-administered
questionnairecomprised of three sections was used to gather the data. A
systematic sampling procedure was appliedto recruit the community residents.
RESULTS: A total of 3410 participants completed the questionnaire survey. It
showed that in highlyeducated residents, 33.4% (170) knew of the names of 3-10
Chinese herbals, 35.8% (182) knew ofnames of 3-10 traditional Chinese patent
drug. Among all the respondent residents, 80.7% (2753)believed that TCM herbal
therapy and TCM non-drug treatments were effective in diseasetreatment, health
enhancement, 85.7% (2923) had taken traditional Chinese patent drug in their
life,56.8% (1937) of residents had used herbal decoction, 40.0% (1365) had
received non-drug treatmentof TCM, such as acupuncture, massage, cupping,
auricular acupuncture. Among the elderly residents,11.4% (98) often used Chinese
patent drug and 9.8% (85) often used herbal decoction. In addition,70.8% (2415)
of residents were willing to accept knowledge and information on TCM for
healthenhancement and disease prevention, such as medicated diet, medicinal tea,
Tai Chi and Qi Gong, although82.8% (2825) of residents had never used them.
CONCLUSION: Chinese patent drug and herbal decoction are widely used in the
communities in Beijing,and there existed a possible close correlation between
high educational level and better understandingof TCM. Age and occupation also
correlated with the attitude to TCM therapies. The characteristicsof the
residents should be considered seriously in the course of promoting the
understandingand application of TCM.
PMID- 29961273
TI - Effect of electroacupuncture on gene expression in calcium signaling pathway in
hippocampal cells in mice with cerebral ischemia reperfusion.
AB - OBJECTIVE: To observe the regulation of electroacupuncture on gene expression at
calcium signalingpathways in mice with cerebral ischemia reperfusion. METHODS:
Sixty male, inbred Kunming mice were randomly assigned to three groups: repeated
cerebralischemia reperfusion group (RG, n = 24), sham-operated group (SG, n =
12), and electroacupuncturegroup (EG, n = 24). Mice in RG and EG groups were
modeled by repeated cerebral ischemiareperfusion surgery, and EG mice were
treated with electroacupuncture for 30 min after recoveryfrom anesthesia. Changes
in gene expression profile of mice hippocampi were analyzed by globalexpression
profile microarray. Genes that were up-regulated or down-regulated greater than
1.5folds were considered to be biologically meaningful. Real-time quantitative
polymerase chain reaction(q-PCR) method was used to verify the expression of
selected genes based on the algorithm [2^(DeltaDeltaCt)]. RESULTS: Compared with
SG mice, 242 genes showed different in expressions in RG mice: 107down-regulated
and 135 up-regulated. Compared with RG mice, 609 genes showed a difference of
expressionin EG mice: 315 down-regulated and 375 up-regulated. Gene ontology and
Kyoto Encyclopediaof Genes and Genomes analyses indicated two pathways: calcium
signaling and long-term potentiationin which 11 differentially expressed genes
selected. Six of the 11 genes in the calcium signalingpathway were verified after
real-time q-PCR testing. CONCLUSION: Electroacupuncture treatment of cerebral
ischemia reperfusion appears to regulateAtp2a2, Cacna1e, Camk2a, Gnas, Grm1,
Rapgef3 genes in the calcium signaling pathway.
PMID- 29961276
TI - [To raise standards in the diagnosis and management of gestational trophoblastic
diseases and concern about quality of life of peri-chemotherapy patients].
PMID- 29961275
TI - Mechanism of herbal pairs with the properties of Qi-tonifying, blood activation,
blood-stasis breaking in treating coronary heartdisease.
PMID- 29961277
TI - [Clinical outcome of patients with gestational trophoblastic neoplasia receiving
primary treatment at Peking Union Medical College Hospital: a 30-year
retrospective cohort study].
AB - Objective: To summarize and analyze the clinical outcomes of gestational
trophoblastic neoplasia (GTN) patients receiving primary treatment at Peking
Union Medical College Hospital from 1985 to 2015, and investigate the changes in
treatment efficacy between the first and the second 15 years. Methods: Clinical
data of GTN patient receiving primary chemotherapy at Peking Union Medical
College Hospital from January 1985 to December 2015 were retrospectively
analyzed. It further compared the therapeutic results and chemotherapy cycles
given to GTN patients, according to International Federation of Gynecology and
Obstetrics (FIGO, 2000) prognostic score system, who were classified to different
stages and low- or high-risk groups. Results: In total, 1 711 GTN patients were
included in this study. Comparing the 1985-2000 group and the 2001-2015 group,
the results showed that: (1) while the overall complete remission (CR) rate was
93.7% (1 603/1 711) , the CR rate of 2001-2015 group was significantly higher
than that of 1985-2000 group [98.4% (1 155/1 174) vs 83.4% (448/537) ,
chi(2)=139.353, P<0.01]. This difference was significant between stage III and IV
patients, but nonexistent between stage I and II patients, including low- and
high-risk groups. (2) The relapse rate of patients who had been in CR was 2.7%
(43/1 603) , with no significant differences between the groups of 1985-2001 and
2001-2015 [3.6% (16/448) vs 2.3% (27/1 155) , chi(2)=6.867, P=0.142]. (3) The
overall mortality rate was 2.6% (44/1 711) , which significantly decreased in
2001-2015 group compared to 1985-2000 group [1.6% (19/1 174) vs 4.7% (25/537) ,
chi(2)=13.830, P<0.01]. This difference appeared only in high-risk patients with
stage III disease (chi(2)=9.505, P<0.01) . (4) Fluorouracil was gradually
replaced by floxridine in chemotherapy regimens. The total cycles of chemotherapy
regimens given to low-risk patients with stage III disease significantly
decreased in 2001-2015 group, but no statistical difference was shown with
patients at other stages. Moreover, the cycles of consolidation treatment were
significantly reduced in patients with stage III patients. Conclusions: GTN
patients could obtain satisfactory curative results after appropriate and
standard treatment. Peking Union Medical College Hospital has achieved better
curative effect in the latest 15 years than before.
PMID- 29961278
TI - [EMA/CO regimen for chemotherapy 24 patients with ultra high-risk gestational
trophoblastic neoplasia].
AB - Objective: To evaluate etoposide, methotrexate and dactinomycin (EMA)
/cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk
gestational trophoblastic neoplasia (GTN) . Methods: A total of twenty-four ultra
high-risk patients who had International Federation of Gynecology and Obstetrics
(FIGO) prognostic scores greater or equal to 12 with liver, brain, or extensive
metastases did poorly when treated with primary chemotherapy admitted in Women's
Hospital, School of Medicine, Zhejiang University from January 2001 to December
2015. All of the patients were treated by EMA/CO regimen and followed up to death
or December 2017. The clinical data of patients were analyzed retrospectively and
the efficacy and toxicity of EMA/CO were evaluated. Results: All of the cases
with ultra high-risk GTN had FIGO prognostic scores >=12 (ranged 12-18, median
13.0) . Twenty patients (83%, 20/24) received EMA/CO regimen as primary treatment
and 4 patients (17%, 4/24) had a history of failed chemotherapy. Seven patients
(29%, 7/24) had metastasis of liver or brain and 17 patients (71%, 20/24) had no
metastasis of liver and brain. Twenty-four patients received totally 167 courses
of EMA/CO regimen (average 7.0 courses) . Sixteen patients achieved complete
remission and 8 patients showed drug-resistant. The complete remission rate was
67% (16/24) and the resistance rate was 33% (8/24) . Of the 16 patients who got
complete remission, 6 cases were treated with EMA/CO regimen alone, and 10 cases
were treated by chemotherapy combined with surgery. For the 8 patients who showed
drug-resistant to EMA/CO, 5 cases of them received EMA/etoposide and cisplatin
(EP) regimen and 3 cases got remission, 1 case received methotrexate,
dactinomycin and cyclophosphamide (MAC) regimen and got remission, 2 cases gave
up treatment because of economic factors. The side effects of EMA/CO mainly
included III-IV degree neutropenia, anemia and alopecia. The incidence of III-IV
degree neutropenia during the treatment of EMA/CO was 21.6% (36/167) , the
incidence of anemia was 96.4% (161/167) , and the incidence of alopecia was 60.5%
(101/167) . In these 24 ultra high-risk GTN patients, 4 patients died during
follow-up. In the 20 patients who got complete remission, no recurrence or
secondary tumor by chemotherapy were occurred. Conclusion: EMA/CO is an effective
regimen with manageable toxicity for patients with ultra high-risk GTN.
PMID- 29961279
TI - [Impact of chemotherapy on ovarian function and quality of life of patients with
gestational trophoblastic neoplasia].
AB - Objective: Using a questionnaire to evaluate different regimens of chemotherapy
on ovarian function and quality of life of patients with gestational
trophoblastic neoplasia (GTN) . Methods: At least 6 months after completion of
chemotherapy, 200 patients with GTN treated in Peking Union Medical College
Hospital from January 2010 to June 2017 were randomly selected to fill up the
questionnaire. The questionnaire items were included the patient's menstrual
cycles, sexual life, gestational issues and common health. The patients were
divided into 3 groups by chemotherapy regimens: actinomycin D (Act-D) group,
floxuridine+Act-D+vincristine (FAV) or floxuridine+Act-D+etoposide+vincristine
(FAEV) group (FAV-FAEV group) , and etoposide+methotrexate+Act-D (EMA)
/vincristine+cyclophosphamide (CO) or EMA/ etoposide+cisplatin (EP) group (EMA/CO
EMA/EP group) . Chi-square test was used with a significance level of P-value
less than 0.05. Results: One hundred and seventy-three (86.5%,173/200) of the
patients completed the questionnaire. Forty three point two percent (43.2%,
19/44) in the EMA/CO-EMA/EP group had a normal menstrual cycle, which were
significantly lower than those of Act-D group (84.6%,22/26) and FAV-FAEV group
(71.2%, 37/52; all P<0.05) . Amenorrhea rate was also significantly higher in
EMA/CO-EMA/EP group (25.0%, 11/44) than in Act-D group (0) and FAV-FAEV group
(17.3%, 9/52; all P<0.05) . The sexual life parameters were comparable among 3
groups. Ten out of thirty-two patients conceived after chemotherapy, 2 had
miscarriages and 8 had full-term delivery of healthy babies. The common health
and labor capacity were significantly decreased after chemotherapy (all P<0.05) .
Conclusions: EMA/CO or EMA/EP regimen have a worse impact on ovarian function
than Act-D and FAV or FAEV regimen. Gynecologic oncologist should be concerned
about the ovarian function and quality of life of GTN patients.
PMID- 29961280
TI - [Application of chest CT scan in gestational trophoblastic neoplasia with lung
metastasis].
AB - Objective: To explore the role of CT scan for the diagnosis of lung metastasis in
stage III gestational trophoblastic neoplasia (GTN) . Methods: To figure out the
role of CT scan for lung metastasis in GTN initial diagnosis, treatment and
follow-up, 93 GTN patients with lung metastasis from January, 2015 to December,
2016 were retrospectively analyzed in Obstetrics and Gynecology Hospital of Fudan
University. Results: (1) Among 93 GTN patients with lung metastasis, 70 patients
with the International Federation of Gynecology and Obstetrics (FIGO) score <=6
were defined as low risk GTN and 23 patients score score >=7 were defined as high
risk GTN. Forty nine patients had negative chest X-ray findings and 39 cases with
pulmonary lesions were identified both by chest X-ray compared to CT scan. Five
cases were excluded due to no consensus could make for the results of chest X
ray. The true positive rate of chest X-ray for lung metastasis were 41% (29/70)
in low risk GTN and 43% (10/23) in high risk GTN patients without statistical
difference (chi(2)=0.090, P=0.925) . For those patients with positive chest CT
scan and negative chest X-ray finding, pulmonary lesions in 32 (65%, 32/49) cases
were blocked by heart, chest wall or diaphragm in chest X-ray. Seventeen
(35%,17/49) patients with lung lesions less than 5 mm had negative chest X-ray
results due to the lower sensitivity compared to CT scan. (2) In 88 patients with
stage III, 78 patients had successful initial treatment, but 4 of them were
recurrence in twelve months follow-up. Ten patients were chemotherapy resistance
for the initial treatment. The initial chemotherapy remission rate in low risk
GTN patients was higher than that in high risk ones (chi(2)=4.911, P=0.027) . In
49 cases with negative chest X-ray, there was no correlation with the rate of
remission,chemotherapy resistance and recurrence in stage III patients (P>0.05) .
(3) For those patients who had poorly response to initial chemotherapy, the
diameters of lesions in lung were unchanged or increased during the treatment,
form (5.1+/-4.1) mm to (7.4+/-2.8) mm. The pulmonary lesions were continuously
shrunk from (7.8+/-5.3) mm to (4.7+/-4.4) mm for those patients with complete and
partial remission including the recurrent GTN patients (Z=-2.713, P=0.007) .
Conclusions: Patients with GTN in stage III have down staging if only use chest X
ray for imaging at the initial diagnosis. Chest CT scan is recommended for
primary imaging evaluation of FIGO staging in qualified medical organization. For
those patients with persistent abnormal serum hCG level and negative chest X-ray,
chest CT scan is strongly recommended to identify the persist or resistant lung
lesions and follow up.
PMID- 29961282
TI - [Expert consensus on diagnosis and treatment of perimenopausal abnormal uterine
bleeding].
PMID- 29961281
TI - [Clinical significance of centralized surveillance of hydatidiform mole].
AB - Objective: To explore the clinical significance of centralized surveillance of
hydatidiform mole. Methods: From Feb. 2013 to Feb. 2017 all patients with
hydatidiform mole, who underwent suction curettage and were confirmed by
histopathology in Dalian Maternal and Child Health Care Hospital, were registered
centrally for serum hCG monitoring and treatment if necessary. Prophylactic
chemotherapy was not administered regardless of risk factors for malignant
transformation of hydatidiform mole. The risk factors included age of over 40
years, excessive uterine enlargement for presumed gestational age, a serum hCG
level greater than 5 00 000 U/L, large theca lutein ovarian cysts (>6 cm), and a
history of previous hydatidiform mole. The centralized surveillance of
hydatidiform mole was based on the central pathology review, team cooperation and
service improvement. Their treatments and outcomes were analyzed retrospectively.
Results: A total of 407 women of hydatidiform mole were registered with
histopathology confirmation, including 70 high-risk hydatidiform moles. The
follow-up rate was 97.5% (397/407) . The incidence of post-mole neoplasia was
8.1% (32/397) , which was diagnosed in 22.9% (16/70) of high-risk and in 4.9%
(16/327) of low-risk hydatidiform moles, showed statistically significant
difference between high-risk and low-risk groups (chi(2)=25.108, P<0.01) . Thirty
two patients with post-mole neoplasia were all at low risk of International
Federation of Gynecology and Obstetrics (FIGO) score (range, 0-6) and received
complete remission with chemotherapy alone in 31 of them except one treated by
hysterectomy. The primary cure rate of single-agent chemotherapy was 60.0%
(18/30) . Patients with low-risk or high-risk post-mole neoplasia were both 16.
There were no significant differences between the two groups in interval that was
end of antecedent pregnancy to start of treatment, the serum level of hCG before
treatment, clinical stage or risk factor score (all P>0.05) . Conclusions: The
risk of malignant transformation is increased in high-risk hydatidiform mole,
however, the high risk factor itself does not affect the prognosis in patients
with timely diagnosis and treatment of post-mole neoplasia. Therefore,
prophylactic chemotherapy is not recommended to high-risk hydatidiform mole
patients. Centralized surveillance of hydatidiform mole is practical in a local
hospital of China and could greatly improve the prognosis of post-mole neoplasia.
PMID- 29961283
TI - [Effects of dyslipidemia on IVF/ICSI pregnancy outcome in patients with
polycystic ovary syndrome].
AB - Objective: To investigate the impact of dyslipidemia on in-vitro fertilization or
intracytoplasmic sperm injection (IVF/ICSI) pregnancy outcome in patients with
polycystic ovary syndrome (PCOS) . Methods: From July 2013 to March 2016, 468
PCOS patients with antagonist protocol in IVF/ICSI of First Affiliated Hospital
of Nanjing Medical University, cycles were divided into dyslipidemia group (108
cases) and normol blood lipids group (360 cases) according to the serum
cholesterol, triglyceride (TG) , high-density lipoprotein, low density
lipoprotein levels. The general condition and clinical outcomes of the two groups
were analyzed retrospectively, including the implantation rate, clinical
pregnancy rate, live birth rate and the incidence of moderate to severe ovarian
hyperstimulation syndrome (OHSS) , etc. Besides, stratified analysis and
multivariate logistic regression analysis were used to correct the impact of body
mass index (BMI) . Results: (1) Comparing the based data of dyslipidemia group
and normal blood lipids group: age, years of infertility, basic FSH, basic LH,
basic estradiol and other indexes had no significant differences (all P>0.05) ,
but BMI of dyslipidemia group was significantly higher than normal blood lipids
group [ (25.0+/-3.0) versus (23.1+/-3.0) kg/m(2)], difference had statistical
significance (P<0.01) . (2) The high score embryo rate, endometrial thickness on
the day of hCG injection, progesterone and LH levels on the day of hCG injection,
moderate to severe OHSS rate and miscarriage rate in the two groups did not
exhibit remarkable differences (all P>0.05) . However, the number of dominant
follicle, retrieved oocyte number, estrogen level on the day of hCG injection,
implantation rate, biochemical pregnancy rate, clinical pregnancy rate and the
live birth rate in dyslipidemia group were significantly less than those of
normal blood lipids group (all P<0.05) , the dose of gonadotropin (Gn) and days
of stimulation were significantly higher compared with the normal blood lipids
group, there were significant differences statistically (all P<0.05) . (3)
Stratified analysis showed that no matter in BMI<24 or BMI>=24 kg/m(2) group, the
dose of Gn and days of stimulation were significantly higher in the dyslipidemia
group than those of the normal blood lipids group, the difference was
statistically significant (P<0.05) . However, the number of oocytes retrieved,
estrogen level on the day of hCG injection had obvious downtrend, and the
difference was statistically significant (P<0.05) in BMI>=24 kg/m(2) group.
Multivariate logistic regression analysis found that, even after the correction
of BMI, dyslipidemia still had negative impact on implantation rate, biochemical
pregnancy rate, clinical pregnancy rate and the live birth rate (P<0.05) . (4)
Further analysis of the different components of blood lipids in the clinical
pregnancy group and unobtained pregnancy group revealed that the level of
triglyceride (TG) in the unobtained pregnancy group was significantly higher than
that in the pregnancy group, and the difference was statistically significant
(P<0.05) ; logistic regression analysis also showed that the increase of TG
levels was negatively correlated with the clinical pregnancy rate of PCOS
patients (P<0.05) . Conclusions: PCOS patients combined with dyslipidemia have a
higher BMI, and dyslipidemia increases the dosage of Gn, reduces the implantation
rate, clinical pregnancy rate and live birth rate, especially the increase of TG
level,which has adverse effects on IVF/ICSI outcome in patients with PCOS.
PMID- 29961284
TI - [Efficacy and safety of low-dose levonorgestrel-releasing intrauterine system in
Chinese women: a multicenter, single-arm, open labeled interventional trial].
AB - Objective: To evaluate the efficacy, bleeding profile and safety of low-dose
levonorgestrel-releasing intrauterine system (LNG-IUS 8) in Chinese healthy women
of childbearing age. Methods: A multi-center, open-label, single-arm clinical
trial conducted at 16 centres in China enrolled 773 healthy women of childbearing
age (mean age 31.6 years old, range 18 to 40 years old) , who demanded
contraception, from April 2006 to June 2013. All women placed LNG-IUS 8 for 3
years and then been followed up at 3, 6, 9, 12, 18, 24, 30, 36 months. The
efficacy variables including pregnancy rate and expulsion rate were analyzed
using life table, while observing adverse events (AE) to evaluate the safety. The
bleeding profile happened during the study was assessed using 90-day reference
intervals (World Health Organization criteria) . Results: Eight pregnancies
occurred among 773 women, resulting in a overall Pearl index of 0.42 per 100
women years. The 3-year cumulative pregnancy rate was 0.37 per 100 women years
and the 3-year cumulative expulsion rate was 1.99 per 100 women years. The number
of women with bleeding/spotting reduced and the bleeding/spotting days declined
over time. Totally 219 AE were reported related to LNG-IUS 8 placements. The most
common AE were vaginal bleeding (8.2%, 63/773) and the ovarian cyst (6.2%,
52/773) . LNG-IUS 8 had an improving effect on dysmenorrhea that the percentage
of women with dysmenorrhea as well as the days of dysmenorrhea decreased over
time. The percentage of women satisfied or very satisfied with LNG-IUS 8 was
87.2% (622/713) . Conclusion: LNG-IUS 8 is highly effective and safe for Chinese
healthy women of childbearing age.
PMID- 29961285
TI - [Reflection on rescue and treatment of mass burn casualties in 21st century].
AB - The rescue and treatment of mass burn casualties is a test for both the burn
treatment level and the disaster emergency response ability of a country or a
region. In recent years, burn disasters happened occasionally around the world
despite of the improvement of safety level in production and the awareness of
fire prevention. On one hand, mass burn casualty events caused catastrophic
damages to human health. On the other hand, they also promoted the development of
burn treatment and disaster medicine. This paper may provide some references for
further improving the management of mass burn casualties in the future by
reviewing several typical cases of burn disaster rescue and treatment in the
world since the 21st century.
PMID- 29961286
TI - [Reflection on rescue and treatment of mass burn patients involved in August 2nd
Kunshan factory aluminum dust explosion accident].
AB - The treatment of mass burn patients is related to social stability, life saving,
and disability reducing. It is also an important opportunity to accumulate,
summarize, and improve clinical rescue and treatment experience. Aiming at August
2nd Kunshan factory aluminum dust explosion, this article reviews and summarizes
experience and problems about rescue reserve, first-aid system, multidisciplinary
cooperation, and integration of usual time and emergent time treatment, so as to
propose corresponding strategies and provide reference for the treatment of mass
burn patients and critically burned patients.
PMID- 29961287
TI - [Challenges for rescue and treatment of mass burns: the experience of rescue and
treatment for casualties in August 2nd Kunshan factory aluminum dust explosion
accident].
AB - The Kunshan factory aluminum dust explosion accident in August 2nd, 2014 caused
the largest number of serious burn casualties in China in the recent 30 years.
With the support of the whole country and the multidisciplinary cooperation, 185
severely burned patients were rescued and treated at 20 hospitals in Jiangsu
province and Shanghai with satisfactory results. The rescue and treatment of mass
burn is a complicated and systematic project on account of its suddenness,
uncertainty, and non-repeatability. The treatment of this explosion accident was
reviewed in this paper to explore the treatment model and experience of
multidisciplinary cooperation. It is worthy to ponder and explore how to face
challenges and strive to improve the treatment level of mass burns.
PMID- 29961288
TI - [Analysis on treatment of eight extremely severe burn patients in August 2nd
Kunshan factory aluminum dust explosion accident].
AB - Objective: To summarize the measures and experience of treatment in mass
extremely severe burn patients. Methods: The clinical data and treatment of 8
extremely severe burn patients in August 2 Kunshan factory aluminum dust
explosion accident who were admitted in the 100th Hospital of PLA on August 2nd,
2014, were retrospectively analyzed. There were 4 males and 4 females, aging 22
45 (34+/-7) years, with total burn area of 55%-98% [(89+/-15)%] total body
surface area (TBSA) and full-thickness burn area of 45%-97% [(80+/-21)%] TBSA.
All the 8 patients were accompanied with severe shock, inhalation injury, and
blast injury. According to the requirements of former PLA General Logistics
Department and Nanjing Military Command, a treatment team was set up including a
special medical unit and a special care unit, with Chai Jiake from the First
Affiliated Hospital of PLA General Hospital as the team leader, Zheng Qingyi from
the 175th Hospital of PLA (the Affiliated Dongnan Hospital of Xiamen University)
as the deputy leader, the 100th Hospital of PLA as the treatment base, and burn
care, respiratory, nephrology, nursing specialists from the First Affiliated
Hospital of PLA General Hospital, and the burn care experts and nursing staff
from the 180th Hospital of PLA, 118th Hospital of PLA, 98th Hospital of PLA, and
175th Hospital of PLA, and nurses from the 85th Hospital of PLA, 455th Hospital
of PLA, 101th Hospital of PLA, 113th Hospital of PLA as team members. Treatment
strategies were adopted as unified coordination by the superior, unified
responsibility of team leader, division of labor and cooperation between team
members, and multidisciplinary cooperation led by department of burns. With
exception of one patient who received deep vein catheterization before admission,
the other 7 patients were treated with deep vein catheterization 0.5 to 3.0 hours
after admission to correct hypovolemic shock as soon as possible. Eight patients
received tracheotomy, and 7 patients were treated with mechanical ventilation by
ventilator in protective ventilation strategy with low tide volume and low volume
pressure to assist breathing. Fiberoptic bronchoscopy was done one to three times
for all the 8 patients to confirm airway injuries and healing status.
Escharectomy and Meek dermatoplasty in the extremities of all the 8 patients were
performed 3 to 6 days after injury for the first time. Escharectomy, microskin
grafting, and covering of large pieces of allogeneic skin on the trunks of 4
patients were performed 11 to 16 days after injury for the second time. The broad
spectrum antibiotics were uniformly used at first time of anti-infective therapy,
and then the antibiotics species were adjusted in time. The balance of internal
environment was maintained and the visceral functions were protected. One special
care unit was on responsibility of only one patient. Psychological intervention
was performed on admission. The rehabilitative treatment was started at early
stage and in company with the whole treatment. Results: Acute renal injury
occurred in 5 patients within 36 hours after injury and their renal function was
restored to normal 4 days after injury due to active adjustment of fluid
resuscitation program. No pulmonary complications, such as severe pulmonary
infection and ventilator-associated pneumonia, occurred in the survived patients.
One of the 8 patients died, and the other 7 patients were cured successfully. The
wounds were basically healed in 2 patients in 26 or 27 days by 2 or 3 times of
operation, and in 5 patients by 4 or 5 times of operation. The basic wound
healing time was 26-64 (48+/-15) days for all the 7 patients. Conclusions:
Treatment strategies of unified coordination by the superior, unified
responsibility of team leader, division of labor and cooperation between team
members, and multidisciplinary cooperation led by department of burns are the
bases to successful treatment. Correcting shock as soon as possible is the
prerequisite and closing wound as soon as possible is the key to successful
treatment. Comprehensive treatment measures, such as maintaining and regulating
the function of viscera, improving the body immunity, and preventing and treating
the complications, are the important components to successful treatment. It is
emphasized that in the treatment of mass extremely severe burn patients,
specialist burn treatment should always be in the dominant position, and other
related disciplines may play a part in auxiliary function.
PMID- 29961289
TI - [Experience of wound treatment on extremely severe mass burn patients involved in
August 2nd Kunshan factory aluminum dust explosion accident].
AB - Objective: To explore experience of wound treatment of extremely severe mass burn
patients involved in August 2nd Kunshan factory aluminum dust explosion accident.
Methods: On August 2nd, 2014, 98 extremely severe burn mass patients involved in
August 2nd Kunshan factory aluminum dust explosion accident were admitted to 20
hospitals in China. The patients with complete medical record were enrolled in
the study and divided into microskin graft group with 56 patients and Meek skin
graft group with 42 patients. Split-thickness skin in area of residual skin were
resected to repair wounds of patients in microskin graft group and Meek skin
graft group by microskin grafting and Meek miniature skin grafting, respectively.
The residual wound size on 28 days post injury and wound infection after skin
grafting of patients in the two groups, and position of donor site of all
patients were retrospectively analyzed. Data were processed with t test and chi
square test. Results: The size of residual wound of patients in Meek skin graft
group on 28 days post injury was (59+/-13)% total body surface area (TBSA), which
was obviously smaller than that in microskin graft group [(70+/-14)%TBSA,
t=4.379, P<0.05]. Twenty-nine patients in microskin graft group and 11 patients
in Meek skin graft group suffered from obvious wound infection after skin
grafting. Wounds of patients in two groups were repaired with residual skin
around wound in head, trunk, groin, armpit, and uncommon donor sites of scrotum
(4 patients), vola (10 patients), and toe or finger web (8 patients).
Conclusions: Meek skin graft is the first choice for wound repair of extremely
severe burn mass patients, with faster wound healing, less wound infection.
Uncommon donor sites of scrotum, vola, and toe or finger web can also be used for
wound repair in case of lack of skin.
PMID- 29961290
TI - [Comparison of machine learning method and logistic regression model in
prediction of acute kidney injury in severely burned patients].
AB - Objective: To build risk prediction models for acute kidney injury (AKI) in
severely burned patients, and to compare the prediction performance of machine
learning method and logistic regression model. Methods: The clinical data of 157
severely burned patients in August 2nd Kunshan factory aluminum dust explosion
accident conforming to the inclusion criteria were collected. Patients suffering
AKI within 90 days after admission were enrolled in group AKI, while the others
were enrolled in non-AKI group. Single factor analysis was used to choose
independent factors associated with AKI, including sex, age, admission time,
features of basic injuries, initial score on admission, treatment condition, and
mortality on post injury days 30, 60, and 90. Data were processed with Mann
Whitney U test, chi-square test, and Fisher's exact test. Variables with P<0.1 in
single factor analysis and those with possible clinical significance were brought
into the establishment of prediction model. Logistic regression and XGBoost
machine learning algorithm were used to build the prediction model of AKI. The
area under receiver operating characteristic curve (AUC) was calculated, and the
sensitivity and specificity for optimal threshold value were also calculated for
each model. Nonparametric resampling test was used to compare the significance of
difference of AUC of the two models. Results: (1) Eighty-nine (56.7%) patients
developed AKI within 90 days from admission. Compared with 68 patients in non-AKI
group, 89 patients in group AKI were older (Z=-2.203, P<0.05), with larger total
burn area and full-thickness burn area (Z=-5.200, -6.297, P<0.01), worse acute
physical and chronic health evaluation (APACHE) II score, abbreviated burn
severity index score, and sequential organ failure assessment (SOFA) score on
admission (Z=-7.485, -4.739, -4.590, P<0.01), higher occurrence rate of sepsis
(chi(2)=33.087, P<0.01), higher rates of accepting tracheotomy, mechanical
ventilation, and continuous renal replacement therapy (chi(2)=12.373, 17.201,
43.763, P<0.01), larger first excision area (Z=-2.191, P<0.05), and higher
mortality on post injury days 30, 60, and 90 (chi(2)=7.483, 37.259, 45.533,
P<0.01). There were no statistically significant differences in sex, open
decompression, admission time, 24-hour fluid volume after admission, 48-hour
fluid volume after admission, the first 24-hour urine volume, the second 24 hour
urine volume, the first excision time, and inhalation injury (chi(2)=0.529,
3.318, Z=-1.746, -0.016, -1.199, -1.824, -0.625, -1.747, P>0.05). The rates of
deep vein catheterization of patients in the two groups were both 100%. (2) There
were twenty possible prediction variables for preliminary establishment of model
according to the difference results of single factor analysis and clinical
significance of variables. (3) The logistic regression prediction model had three
variables: APACHE II score [odds ratio (OR)=1.36, 95% confidence interval
(CI)=1.20-1.53, P<0.001], sepsis (OR=2.63, 95% CI=0.90-7.66, P>0.05), and the
first 24-hour urine volume (OR=0.71, 95% CI=0.50-1.01, P>0.05). The AUC of the
logistic regression prediction model was 0.875 (95% CI=0.821-0.930), with the
specificity and sensitivity of optimal threshold value 84.4% and 77.7%,
respectively. (4) XGBoost machine learning model had seven main predictive
variables: APACHE II score, full-thickness burn area, 24-hour fluid volume after
admission, sepsis, the first 24-hour urine volume, SOFA score, and 48-hour fluid
volume after admission. The AUC of machine learning model was 0.920 (95% CI=0.879
0.962), higher than that of logistic regression model (P<0.001), with the
specificity and sensitivity of optimal threshold value 89.7% and 82.0%,
respectively. Conclusions: Sepsis and fluid resuscitation are two important
predictive variables that can be intervened for AKI in severely burned patients.
Machine learning method has a better performance and can provide more accurate
prediction for individuals than logistic regression prediction model, and
therefore has good clinical application prospect.
PMID- 29961291
TI - [Analysis of effects of discipline cooperation on rescue and treatment of severe
mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion
accident].
AB - Objective: To analyze effects of cooperation between physicians in department of
burn surgery and department of intensive care medicine on rescue and treatment of
severe mass burn patients involved in August 2nd Kunshan factory aluminum dust
explosion accident. Methods: On August 2nd, 2014, 15 extremely severe burn
patients involved in August 2nd Kunshan factory aluminum dust explosion accident
were admitted to temporary burn treatment center established in Department of
Critical Care Medicine of the Second Affiliated Hospital of Soochow University.
The 15 patients were equally divided into 3 groups, with 5 patients in each
group. Fifteen surgeons and 30 nurses from department of burn surgery and 15
physicians and 30 nurses from department of intensive care medicine from
different hospitals in China were divided into 3 groups, with 5 physicians and 10
nurses from department of burn surgery and 5 physicians and 10 nurses from
department of intensive care medicine in each group. Each group of physicians and
nurses were responsible for treatment of 5 patients. Treatment of patients was
leaded by surgeons from department of burn surgery, who were responsible for
wound dealing and operation. Physicians from department of intensive care
medicine were responsible for systemic treatment and adjustment of relevant
equipment's parameters. Volume of fluid infusion and urine output in shock
period, severe systemic complication during period of treatment, using time and
kind of antibiotics, death in 1 month after admission, length of hospital stay,
and survival of patients were monitored. Results: Volume of fluid infusion of 15
extremely severe burn patients within the first 24 hours post injury was 10 360
17 162 (12 998+/-1 811) mL, including (1.62+/-0.23) mL.% total body surface area
(TBSA)(-1).kg(-1) electrolyte and colloid and (2 850+/-232) mL glucose, with
electrolyte and colloid ratio of (1.76+/-0.23)?1.00. Volume of urine output
within the first 24 hours post injury was (2 384+/-1 242) mL, with (99+/-52) mL
in each hour. Volume of fluid infusion of 15 extremely severe burn patients
within the second 24 hours post injury was 8 720-11 616 (9 406+/-1 277) mL,
including (1.04+/-0.22) mL.%TBSA(-1).kg(-1) electrolyte and colloid and (2 910+/
187) mL glucose, with electrolyte and colloid ratio of (1.53+/-0.31)?1.00. Volume
of urine output within the second 24 hours post injury of patients was (2 299+/-1
362) mL , with (108+/-61) mL in each hour. One patient had pulmonary infection,
and 7 patients had fungal infection, and no patient had gut microbiota dysbiosis.
Patients were treated with combined 2 kinds of antibiotics for 21-85 (50+/-16) d.
No patient died within 1 month after admission. The length of hospital stay was
53-132 (98+/-44) d. Ten patients survived finally. Conclusions: After being
treated by cooperation between physicians in department of burn surgery and
department of intensive care medicine, severe mass burn patients involved in
August 2nd Kunshan factory aluminum dust explosion accident had hemodynamic
stability and could stably experience shock period, with less complication,
shorter length of hospital stay, no death within 1 month after admission, more
survived patients, which can provide reference for rescue and treatment of severe
mass burn patients.
PMID- 29961292
TI - [Effects of airway management team in the treatment of severely mass burn
patients combined with inhalation injury].
AB - Objective: To explore and analyze the effects of airway management team (AMT) in
the treatment of severely mass burn patients combined with inhalation injury.
Methods: The clinical data of 58 severely burned patients combined with
inhalation injury hospitalized in our unit from January 2012 to August 2014,
conforming to the inclusion criteria, were retrospectively analyzed. According to
whether airway management was implemented by AMT or not, patients hospitalized
from January 2012 to July 2014 were divided into control group (n=27), while
patients in Kunshan factory aluminum dust explosion accident hospitalized on 2nd
August 2014 were divided into observation group (n=31). Patients in control group
received regular airway nursing carried out by nurses on duty, while patients in
observation group received specialized airway concentration nursing implemented
by AMT. The concrete implementation included overall assessment of patients'
airway, elaborate airway care, and controlled management of mechanical
ventilation. Arterial blood gas indexes and oxygenation index of patients in the
two groups on post injury day (PID) 1, 7, and 14 were compared. Sputum viscosity,
ventilator-associated pneumonia (VAP) occurrence rate, and ventilation time of
patients in the two groups in post injury week(s) 1, 2, and 3 after admission
were monitored and recorded. Survival rates of patients in the two groups were
compared. Data were processed with analysis of variance for repeated measurement,
t test and Bonferroni correction, chi-square test, and Wilcoxon rank sum test.
Results: (1) There were no statistically significant differences in pH value,
arterial partial pressure of oxygen (PaO(2)), arterial partial pressure of carbon
dioxide (PaCO(2)), arterial oxygen saturation (SaO(2)), and oxygenation index of
patients in the two groups on PID 1 (t=0.595, -0.166, 1.518, -0.828, 0.458,
P>0.05). The pH values of patients in observation group on PID 7 and 14 were
7.327+/-0.050 and 7.367+/-0.043, respectively, significantly better than those in
control group (7.304+/-0.021 and 7.390+/-0.029, respectively, t=-2.385, 2.391,
P<0.05). The PaO(2) values of patients in observation group on PID 7 and 14 were
(95.1+/-6.7) and (106.3+/-7.8) mmHg (1 mmHg=0.133 kPa), respectively,
significantly higher than those in control group [(91.6+/-5.7) and (102.0+/-8.3)
mmHg, respectively, t=-2.109, -2.059, P<0.05]. The PaCO(2) values of patients in
observation group on PID 7 and 14 were (41+/-4) and (40+/-4) mmHg, respectively,
significantly lower than those in control group [(43+/-5) and (43+/-4) mmHg,
respectively, t=2.220, 2.304, P<0.05]. The SaO(2) values of patients in
observation group on PID 7 and 14 were 0.95+/-0.04 and 0.96+/-0.04, respectively,
significantly higher than those in control group (0.93+/-0.05 and 0.94+/-0.05,
respectively, t=-2.201, -2.016, P<0.05). The oxygenation indexes of patients in
observation group on PID 7 and 14 were (286+/-18) and (329+/-20) mmHg,
significantly higher than those in control group [(277+/-14) and (306+/-58) mmHg,
respectively, t=-2.263, -2.022, P<0.05]. (2) Sputum viscosity of patients in
observation group in post injury week(s) 1, 2, and 3 were superior to that in
control group (Z=-2.096, -2.076, -2.033, P<0.05). (3) VAP occurrence rate of
patients in observation group was lower than that in control group, and time of
mechanical ventilation of patients in observation group was shorter than that in
control group (chi(2)=4.244, t=2.425, P<0.05). (4) Survival rate of patients in
observation group was higher than that in control group (chi(2)=4.244, P<0.05).
Conclusions: The special intensive care of airway management by AMT can
effectively improve the oxygenation status of severely burned patients combined
with inhalation injury, alleviate the sputum viscosity, reduce the occurrence of
VAP, and shorten the time of mechanical ventilation, thus benefits the treatment
of severely mass burn patients combined with inhalation injury.
PMID- 29961293
TI - [Changes of helper T lymphocytes 17 and regulatory T lymphocytes in peripheral
blood of patients with extensive burn at early stage in August 2nd Kunshan
factory aluminum dust explosion accident and the significance].
AB - Objective: To explore the changes of helper T lymphocytes 17 (Th17) and
regulatory T lymphocytes (Tregs) in peripheral blood of patients with extensive
burn at early stage in August 2nd aluminum dust explosion accident in Kunshan
factory (hereinafter referred to as Kunshan explosion accident) and the
significance. Methods: Twenty patients with extensive burn in Kunshan explosion
accident admitted to our department of burns and plastic surgery were enrolled in
burn group, and 10 healthy adult volunteers with no history of smoking were
enrolled in healthy control group. Five mL of peripheral venous blood samples
were collected from patients in burn group at admission (<=post injury hour 6,
PIH 6) and PIH 24, and on post injury day (PID) 7, and from volunteers in healthy
control group respectively. The percentages of CD64(+) T lymphocytes, human
leukocyte antigen-DR positive (HLA-DR(+) ) T lymphocytes, CD3(+) CD8(-) Th17, and
CD4(+) CD25(+) Tregs in peripheral blood T lymphocytes were determined by flow
cytometer. Results: (1) The percentages of CD64(+) T lymphocytes in peripheral
blood T lymphocytes of patients in burn group at admission and PIH 24 [(2.35+/
0.32)% and (4.02+/-0.15)%] were higher than (0.67+/-0.11)% of healthy volunteers
in healthy control group. The percentage of CD64(+) T lymphocytes in peripheral
blood T lymphocytes of patients in burn group on PID 7 [(0.39+/-0.25)% ] was
lower than that of healthy volunteers in healthy control group. The percentages
of HLA-DR(+) T lymphocytes in peripheral blood T lymphocytes of patients in burn
group at admission and PIH 24 [(54+/-18)% and (72+/-17)%] were higher than (38+/
14)% of healthy volunteers in healthy control group. The percentage of HLA-DR(+)
T lymphocytes in peripheral blood T lymphocytes of patients in burn group on PID
7 [(28+/-15)% ] was lower than that of healthy volunteers in healthy control
group. (2) The percentages of CD3(+) CD8(-)Th17 in peripheral blood T lymphocytes
of patients in burn group at admission and PIH 24 [(4.21+/-0.46)% and (7.38+/
0.39)%] were higher than (0.98+/-0.09)% of healthy volunteers in healthy control
group. The percentage of CD3(+) CD8(-)Th17 in peripheral blood T lymphocytes of
patients in burn group on PID 7 [(0.81+/-0.05)% ] was lower than that of healthy
volunteers in healthy control group. (3) The percentages of CD4(+) CD25(+) Tregs
in peripheral blood T lymphocytes of patients in burn group at admission and PIH
24, and on PID 7 [(1.78+/-0.26)%, (1.26+/-0.37)%, and (0.38+/-0.03)%] were lower
than (3.24+/-0.52)% of healthy volunteers in healthy control group. Conclusions:
The percentage of Th17 in peripheral blood T lymphocytes of patients with
extensive burn at early stage in Kunshan explosion accident increased at first
and then decreased compared with that of healthy volunteers, indicating that the
patients' immune function increased first and then weakened. The percentages of
Tregs in peripheral blood T lymphocytes at each time point were lower than the
percentage of healthy volunteers, indicating that the patients' immunomodulation
gradually weakened after extensive burns.
PMID- 29961295
TI - [Effect of continuous plasma filtration adsorption on treatment of severely
burned patients with sepsis].
AB - Objective: To investigate effect of continuous plasma filtration adsorption on
treatment of severely burned patients with sepsis. Methods: In January 2014 to
September 2017, 86 severely burned patients with sepsis, conforming to the study
criteria, were admitted to our hospital and divided into into routine treatment
group and continuous plasma filtration group according to the random number table
method, with 43 patients in each group. Patients in routine treatment group were
treated with routine treatment after admission. Patients in continuous plasma
filtration group were treated with blood filter, blood purification machine, and
plasma separator for continuous plasma filtration adsorption on the basis of the
routine treatment group on the second day after admission. The course of
treatment in the 2 groups was 7 d. The total effective treatment rate, changes of
leukocyte count (WBC), usea nitrogen, serum creatinine, neutrophile CD64,
procalcitonin, and C reactive protein (CRP) before and after treatment, and
mortality on 28 days after treatment of patients in 2 groups were analyzed and
compared. Results: (1) The total effective treatment rate of patients in
continuous plasma filtration group was 88.37% (38/43), which was significantly
higher than that of the routine treatment group [65.12% (28/43), chi(2)=6.515,
P=0.018]. (2) After treatment, WBC, urea nitrogen, serum creatinine, neutrophils
CD64, procalcitonin, and CRP of patients in continuous plasma filtration group
were significantly lower those in routine treatment group (t=6.305, 4.420,
18.537, 13.435, 12.975, 14.234, P<0.05). WBC, urea nitrogen, serum creatinine,
neutrophile CD64, procalcitonin, and CRP of patients in 2 groups after treatment
were significantly lower than those before treatment (t=9.459, 9.130, 25.438,
35.467, 23.471, 23.601, 3.802, 5.662, 12.067, 25.694, 20.720, 12.437, P<0.05).
(3) On 28 days after treatment, mortality of patients in continuous plasma
filtration group was 6.98% (3/43), which was significantly lower than that in
routine treatment group [25.58% (11/43)], chi(2)=5.460, P=0.023. Conclusions:
Continuous plasma filtration adsorption is effective in treating severely burned
patients with sepsis, which can alleviate inflammatory reaction mediated by
inflammatory cytokine with good prognosis.
PMID- 29961294
TI - [Application value of endoscope in probing chronic wound with sinus tract in
clinic].
AB - Objective: To explore the application value of endoscope in probing the chronic
wound with sinus tract in clinic. Methods: Twenty-eight chronic wounds with sinus
tracts from 27 patients conforming to the inclusion criteria admitted to
Outpatient Department of Wound Healing Center of Ruijin Hospital from December
2017 to March 2018 were investigated in a prospective and self-controlled trial.
After being cleaned, the diameter of the opening of sinus tract was measured with
a rule. A probe was used to measure the depth of a sinus tract according to the
touch from the probe extremity in operation, and to measure the depth of a sinus
tract that could be observed with naked eyes with the help of a pair of
hemostatic forceps. Five minutes later, a probe was inserted deeply into the
sinus tract to measure the depth under the endoscopic view combined with touch
from the probe extremity in operation. Afterwards, the sinus tract was observed
with endoscope, and the depth of the tract which could be observed under the
endoscopic view was measured using a probe inserted deeply into the sinus tract.
After completion of the above exploration, the sinus tract was infused with
contrast agent Omnipaque 350 and scanned by computed tomography (CT) later to
obtain its depth. The following indicators were calculated: the ratio of the
depth of the sinus tract measured by CT to the diameter of the opening of the
sinus tract (hereinafter referred to as the depth/diameter ratio of the sinus
tract), the deviation rate comparing the depth of the sinus tract measured by
conventional method (measured by probe only) and by endoscope (measured by probe
under the endoscope view) with the depth of the sinus tract measured by CT
(hereinafter referred to as the deviation rate of the measured depth of the sinus
tract), the deviation rate comparing the depth of the sinus tract that could be
observed measured by conventional method and by endoscope with the depth of the
sinus tract measured by CT (hereinafter referred to as the deviation rate of the
depth of the sinus tract that could be observed). Data were processed with paired
t test. Pearson correlation analysis was applied to analyze the correlation
between the depth/diameter ratio of the sinus tract and the deviation rate of the
measured depth of the sinus tract and the deviation rate of the depth of the
sinus tract that could be observed by conventional method and by endoscope.
Results: The depth/diameter ratio of the sinus tract of this group of wounds was
1-32 (8+/-7). The deviation rate of the measured depth of the sinus tract and the
deviation rate of the depth of the sinus tract that could be observed by
conventional method were (19+/-14)% and (79+/-18)%, respectively, both obviously
larger than (9+/-9)% and (25+/-25)% by endoscope (t=3.837, 13.626, P<0.01).
Positive correlation existed between the depth/diameter ratio of the sinus tract
and the deviation rate of the measured depth of the sinus tract by conventional
method, and between the depth/diameter ratio of the sinus tract and the deviation
rate of the depth of the sinus tract that could be observed by conventional
method and by endoscope (r=0.514, 0.585, 0.651, P<0.01). However, there was no
obvious correlation between the depth/diameter ratio of the sinus tract and the
deviation rate of the measured depth of the sinus tract by endoscope (r=0.113,
P>0.05). Conclusions: Compared with the conventional method, application of
endoscope is able to get more accurate data of chronic wounds with sinus tracts
and observe the wounds with wider range.
PMID- 29961296
TI - [Effect of early supplementation of exogenous carnitine on liver mitochondrial
damage in severely scalded rats and its pathological mechanism].
AB - Objective: To observe the effect of early supplementation of exogenous carnitine
on liver mitochondrial damage in severely scalded rats and to explore its
pathological mechanism. Methods: Seventy-two adult female Sprague-Dawley rats
were divided into sham injury group, scald injury group, and scald injury+
carnitine group according to the random number table, with 24 rats in each group.
Rats in sham injury group was sham injured on the back by immersing in 37 C water
bath for 12 s without fluid replacement. While rats in scald injury and scald
injury+ carnitine groups were inflicted with 30% total body surface area (TBSA)
full-thickness scald on the back by immersing in 98 Cwater bath for 12 s.
Immediately after injury, rats in scald injury group and scald injury+ carnitine
group were injected with Ringer's lactate solution with the dosage of 4 mL.kg(
1).%TBSA(-1) via tail vein according to the Parkland formula, meanwhile rats in
scald injury+ carnitine group were injected with L-carnitine solution with dosage
of 300 mg.kg(-1).d(-1) via tail vein from post injury hour (PIH) 1. At PIH 12,
24, 48 and 72, abdominal aorta blood and liver tissue were collected from 6 rats
in each group. The serum levels of carnitine, beta-hydroxybutyric acid, and
ornithine carbamoyltransferase (OCT) were determined with enzyme-linked immuno
sorbent assay, and the serum levels of lactate dehydrogenase (LDH), alanine
aminotransferase(ALT), and aspartate transaminase (AST) was determined by
automatic biochemical analyzer, Pathological changes of rats liver tissue were
detected with HE staining. Data were processed with analysis of variance of
factorial design and Student-Newman-Keulstest or Tamhane test, Bonferroni
correction. Results: (1) Compared with sham injury group, the serum level of
carnitine of rats in scald injury group was significantly lower at each time
point (P<0.05), and that of scald injury+ carnitine group was significantly lower
at PIH 12, 24, and 48 (P<0.05). The serum level of carnitine of rats in scald
injury+ carnitine group at PIH 72 [(28.2+/-3.0) MUg/mL] was similar to that in
sham injury group[(29.4+/-4.0) MUg/mL, P>0.05]. The serum level of carnitine in
scald injury+ carnitine group was significantly higher than that in scald injury
group at each time point (P<0.05). (2) The serum levels of beta-hydroxybutyric
acid of rats in scald injury group and scald injury+ carnitine group were
significantly lower than those in sham injury group at each time point (P<0.05).
The serum levels of beta-hydroxybutyric acid of rats in scald injury and scald
injury+ carnitine groups both showed a trend of increase, and they peaked at PIH
72 [(1.77+/-0.30) , (2.93+/-0.44) mmol/L, respectively]. The serum levels of beta
hydroxybutyric acid in scald injury+ carnitine group were significantly higher
than those of scald injury group at each time point (P<0.05). (3) The serum
levels of OCT of rats in scald injury and scald injury+ carnitine groups were
significantly higher than those of sham injury group at each time point (P<0.05).
The serum levels of OCT of rats in scald injury group and scald injury+ carnitine
groups both showed a trend of decrease, and they peaked at PIH 12 [(186.28+/
6.77), (163.38+/-9.34) ng/mL, respectively]. The serum levels of OCT of rats in
scald injury+ carnitine group were significantly lower than those of scald injury
group at each time point (P<0.05). (4) Compared with those of sham injury group,
the serum levels of LDH of rats in scald injury group were significantly higher
at each time point (P<0.05). Compared with those of sham injury group, those of
scald injury+ carnitine group were significantly higher at PIH 12 and 24
(P<0.05), which peaked at PIH 12 [(2 226+/-274) U/L]. The serum levels of LDH of
rats in scald injury+ carnitine group were close to those of sham injury group at
PIH 48 and72 (P>0.05). The serum levels of LDH of rats in scald injury+ carnitine
group were significantly lower than those of scald injury group at each time
point (P<0.05). (5) The serum levels of ALT and AST of rats in scald injury group
and scald injury+ carnitine group were significantly higher than those of sham
injury group at each time point (P<0.05). In scald injury+ carnitine group, the
serum levels of ALT of rats were significantly lower than those in scald injury
group at PIH 48 and 72 (P<0.05), and the serum level of AST of rats was
significantly lower than that in scald injury group at PIH 48 (P<0.05), and the
serum levels of AST and ALT of rats were close to those in scald injury group at
other time points (P>0.05). The serum levels of ALT and AST in scald injury+
carnitine group both showed a trend of decrease, and they peaked at PIH 12
[(260+/-25), (1 511+/-145) U/L, respectively]. (6) The liver tissue of rats in
sham injury group was basically normal at each time point. The degree of liver
injury of rats in scald injury+ carnitine group was lighter than that in scald
injury group. The liver tissue of rats in scald injury group at PIH 72 showed
obvious cytoplasm loose, liver tissue structure loss with diffuse fatty
degeneration and large coagulative necrosis. Only partially scattered fatty
degeneration was observed in the liver tissue of ras in scald injury+ carnitine
group. Conclusions: By early supplementation of exogenous carnitine, serum levels
of carnitine and beta-hydroxybutyric acid can be restored to normal levels
faster, alleviate mitochondrial damage of hepatocytes, and maintain the metabolic
stability of hepatocytes in early stage of severe scald.
PMID- 29961298
TI - [Management of analgesia and sedation in critically burned adult patients].
AB - Analgesia and sedation play important roles in the overall treatment of
critically burned adult patients. According to clinical actual situation of
critically burned adult patients, a set of analgesic and sedative practices,
including analgesia-based sedation, scientifically reasonable sedation status
monitoring, early goal-directed sedation strategy, standardized and
individualized strategy for analgesia and sedation, and early comfort using
analgesia, minimal sedative, maximal human care strategy are recommended and
widely implemented nowadays. However, guideline or consensus about how to provide
analgesia and sedation treatment for critically burned adult patients is lacking.
In this article, we discuss strategy for analgesic and sedative management in
critically burned adult patients, with preexisting ideas in critical care
medicine, pathophysiological characteristics of critically burned patients, and
our clinical practice for reference.
PMID- 29961297
TI - [Effect of alprostadil on wound healing of scalded rats and the mechanism].
AB - Objective: To explore effect of alprostadil on wound healing of scalded rats and
the mechanism. Methods: According to random number table method, forty-eight
Sprague Dawley rats were divided into sham scald group, simple scald group,
lithium chloride group, and alprostadil group, with 12 rats in each group. Rats
in sham injury group were sham injured on the back, and rats in the other three
groups were inflicted with 30% total body surface area deep partial thickness
scald on the back.Immediately after scald, rats in sham scald group and simple
scald group were injected with 1 mL saline through caudal vein, and rats in
lithium chloride group and alprostadil group were injected respectively with 1 mL
lithium chloride and alprostadil through caudal vein. Saline, lithium chloride,
and alprostadil were injected once in a day and lasted for 14 days. General wound
appearance and wound healing rate on post scald day (PSD) 7, 10, 14 were observed
and calculated. Expressions of protein and mRNA of Wnt1 and beta-catenin on PSD
14 were detected. Data were processed with analysis of variance of factorial
design, one-way analysis of variance, Student Newman Keuls q test, t test, and
Bonferroni correction. Results: (1) On PSD 7, wounds of scalded rats in each
group formed dry eschar and had little exudation. On PSD 10, wounds of rats in
simple scald group were covered with eschar, with little exudation, and wounds of
rats in lithium chloride group were covered with eschar, and partial wounds
healed under the eschar. On PSD 10, partial eschar of rats in alprostadil group
desquamated; partial wounds healed; newly burned skin was ruddy. On PSD 14,
partial wounds of rats in simple scald group were healed under eschar with little
exudation. On PSD 14, most of the eschar of rats in lithium chloride group were
desquamated with patial wounds healed and little exudation. On PSD 14, wounds of
rats in alprostadil group were basically healed with vigorously growing hair on
the back. (2) On PSD 7, the wound healing rates of rats in simple scald group,
lithium chloride group, and alprostadil group were close (F=0.41, P>0.05). On PSD
10 and 14, wound healing rate of rats in lithium chloride group and alprostadil
group were significantly higher than that in simple scald group (q=5.73, 17.45,
26.30, 11.28, P<0.05), and wound healing rate of rats in alprostadil group was
significantly higher than that in lithium chloride group (q=32.03, 28.73,
P<0.05). (3) On PSD 14, the mRNA expressions of Wnt1 and beta-catenin of rats in
lithium chloride group and alprostadil group were significantly higher than those
in simple scald group (q=65.40, 19.16, 66.79, 18.41, P<0.05), and the mRNA
expressions of Wnt1 and beta-catenin of rats in simple scald group was
significantly higher than those in sham scald group (t=14.86, 4.46, P<0.05). (4)
On PSD 14, the protein expressions of Wnt1 and beta-catenin of rats in lithium
chloride group and alprostadil group were 0.98+/-0.05, 0.98+/-0.06, 0.97+/-0.06,
and 1.00+/-0.06, which were significantly higher than 0.49+/-0.04 and 0.66+/-0.04
of rats in simple scald group (q=34.62, 22.38, 33.61, 23.47, P<0.05). On PSD 14,
the protein expressions of Wnt1 and beta-catenin of rats in simple scald group
was significantly higher than 0.29+/-0.03 and 0.31+/-0.03 of rats in sham scald
group (q=14.73, 23.88, P<0.05). Conclusions: Alprostadil can accelerate wound
healing through activating Wnt/beta-catenin signal pathway and upregulating the
expressions of Wnt1 and beta-catenin.
PMID- 29961299
TI - [Advances in the research of mesenchymal stem cells in chronic wounds].
AB - Skin is the largest organ in the body, with a variety of functions, such as
thermoregulation, physical barriers, and sensory transmission, etc. Therefore, to
restore the function after injury as soon as possible is particularly important.
Mesenchymal stem cells (MSCs) are derived from mesoderm, and can differentiate
into a variety of tissues, such as cartilaginous tissue, myoideum, and adipose
tissue. Weak immunogenicity of MSCs make them become the ideal seed cells of
tissue engineering. MSCs have a wide range of sources, including known sources of
bone marrow, skin, placenta, and adipose tissue, etc. MSCs from different sources
also have many different mechanisms in wound repair. This article reviews the
recent researches on MSCs in the treatment of chronic wounds, so as to explore
new ideas for the clinical treatment of chronic wounds.
PMID- 29961300
TI - [Advances in the research of drug intralesional injection therapy in keloid].
AB - Keloid is characterized by tumor-like invasive growth, high incidence, and low
remission rate. The pathogenesis of keloid is still unknown. Keloids can not only
affect appearance, but also cause severe itching and pain, which may affect
physical and mental health of patients. Previous treatments for keloids include
surgery, drugs, lasers and so on. Due to the high recurrence rate of surgical
treatment accompanied by keloid enlargement, drug therapy has gradually become a
hot topic. Among various methods of administration, intralesional injection is
widely accepted as it can promote drug absorption to achieve better results. The
progress of several drugs used in intralesional injection therapy for keloid is
reviewed in this paper.
PMID- 29961301
TI - [Advances in the research of techniques for traumatic scars intervention with
photoelectric acoustic therapy].
AB - Traumatic scar is a common complication of skin injury, such as burn, trauma, and
surgery. The mechanism for scar formation still remains unclear. Traumatic scar
has a negative impact on the quality of patients' life, due to the appearance of
scar always causes physical or/and psychological problems to patients. The
treatments for scar include surgery, chemotherapy, radiotherapy, and pressure,
depending on the kind of scar present. Recently, a great progress in treating
scar has been achieved by novel techniques with laser, intense pulsed light,
micro-plasma radiofrequency, and ultrasound. The aim of this review is
introducing the advances of these techniques for traumatic scars intervention.
PMID- 29961302
TI - [Advances in the research of application of three-dimensional bioprinting in skin
tissue engineering].
AB - Deep skin wounds require skin grafts for coverage. Current treatments such as
tissue engineered skin or skin substitutes can not meet the needs of clinical
application due to the technical problems involving preservation, transportation,
and a lengthy preparation process. In comparison with traditional methods such as
freeze-drying, three-dimensional bioprinting can precisely dispense living cells,
nucleic acid, growth factor, and phase-changing hydrogels according to the wound
form, while maintaining high cell viability. Besides, it has excellent
performance in high resolution, flexibility, reproducibility, and high
throughput, showing great potential in the fabrication of tissue engineered skin.
This review mainly introduces the common techniques of three-dimensional
bioprinting, and their application in skin tissue engineering, focusing on the
latest research progress, and summarizes the current challenges and future
development of three-dimensional skin printing.
PMID- 29961303
TI - Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke.
PMID- 29961304
TI - Susceptibility Vessel Sign in the ASTER Trial: Higher Recanalization Rate and
More Favourable Clinical Outcome after First Line Stent Retriever Compared to
Contact Aspiration.
PMID- 29961305
TI - Journal metrics of Clinical and Molecular Hepatology based on the Web of Science
Core Collection.
AB - Background/Aims: Eight years have passed since Clinical and Molecular Hepatology
changed its language policy to English-only in September 2010. The journal has
been included in PubMed Central since September 2010. Present title continues the
Korean Journal of Hepatology since June 2012. It has been indexed in the Web of
Science Core Collection as an Emerging Sources Citation Index journal since 2015.
I sought to determine whether the change in language policy was successful based
on journal metrics. I also investigated whether the journal has become one of the
top-ranked world journals in the category of gastroenterology and hepatology.
METHODS: The following journal metrics were calculated or analyzed based on the
journal's bibliographic information from 2012 to 2017 and the Web of Science Core
Collection database: citable and non-citable articles, country of authors, total
cites, impact factor, the immediacy index, country of citing authors, citing
journal titles, and the Hirsch index. RESULTS: From 2012 to 2017, there were 282
citable articles. Authors from 29 countries have published in the journal. The
number of total citations in 2017 was 611. The impact factor increased from 2.1
in 2014 to 2.8 in 2017. The citing authors were from 85 countries, and their
papers have been cited in 663 journals. The Hirsch index was 19. Conclusions:
Based on journal metrics, Clinical and Molecular Hepatology has succeeded in
becoming a top-ranked international journal 8 years after changing its language
policy to English-only.
PMID- 29961306
TI - Intravascular imaging analysis of a drug-eluting balloon followed by a bare metal
stent compared to a drug-eluting stent for treatment of de novo lesions.
AB - Background/Aims: After a study comparing drug-eluting stents (DESs) to sequential
treatment with drug-eluting balloons (DEBs) and bare metal stents (BMSs), we
retrospectively analysed strut malapposition and neointimal hyperplasia in de
novo coronary lesions using optical coherence tomography (OCT) or intravascular
ultrasonography (IVUS). Methods: We obtained OCT data from 16 patients (eight per
group) and IVUS data from 40 patients (20 per group). OCT or IVUS was performed
after the index procedure and after 9 months. Parameters including obstruction
volume due to neointimal hyperplasia (neointimal hyperplasia volume/stent volume,
%), strut malapposition (% of malapposed struts), and intra-individual
inhomogeneity of in-stent restenosis were compared. Results: Although obstruction
volume due to neointimal hyperplasia was significantly higher in the DEB-BMS
group (14.90 +/- 15.36 vs. DES 7.03 +/- 11.39, p = 0.025), there was no
difference in strut malapposition between the two groups (DEB-BMS 1.99 +/- 5.37
vs. DES 0.88 +/- 2.22, p = 0.856). The DEB-BMS group showed greater intra
individual inhomogeneity of in-stent restenosis pattern than the DES group.
Conclusions: Treatment with DEB followed by BMS failed to improve strut
malapposition despite higher in-stent neointimal growth, probably because of the
inhomogeneous inhibition of in-stent neointimal hyperplasia by DEB. DEB
technology should be improved to obtain even drug delivery to the vessel wall and
homogeneous prevention of neointimal growth comparable to contemporary DES.
PMID- 29961307
TI - Applications of kidney organoids derived from human pluripotent stem cells.
AB - The establishment of protocols to differentiate kidney organoids from human
pluripotent stem cells provides potential applications of kidney organoids in
regenerative medicine. Modeling of renal diseases, drug screening, nephrotoxicity
testing of compounds, and regenerative therapy are attractive applications.
Although much progress still remains to be made in the development of kidney
organoids, recent advances in clustered regularly interspaced short palindromic
repeat (CRISPR)-CRISPR-associated system 9 (Cas9) genome editing and three
dimensional bioprinting technologies have contributed to the application of
kidney organoids in clinical fields. In this section, we review recent advances
in the applications of kidney organoids to kidney disease modelling, drug
screening, nephrotoxicity testing, and regenerative therapy.
PMID- 29961308
TI - Clinical usefulness of bioimpedance analysis for assessing volume status in
patients receiving maintenance dialysis.
AB - Chronic volume overload is associated with left ventricular hypertrophy and high
cardiovascular mortality in patients undergoing dialysis. Therefore, estimating
body fluid status is important in these patients. However, most dry-weight
assessments are still performed clinically, while attempts have been made to
measure the volume status and dry weight of patients undergoing dialysis using
bioimpedance analysis (BIA). BIA uses the electrical properties of the human body
to alternate current flow and measures resistance values to estimate body water
content and composition. BIA is divided into single-frequency BIA, multi
frequency BIA, and bioimpedance spectroscopy (BIS) according to the number of
frequencies used, and into whole-body and segmental BIA according to whether or
not the whole body is divided into segments. Extracellular water (ECW),
intracellular water, and total body water (TBW) contents can be measured with
BIA. Dry weight can be estimated by measuring the volume overload of the patient
through the ECW/TBW and ECW-to-body weight ratios. Other estimation methods
include the normovolemia/hypervolemia slope method, a resistance-reactance (RXc)
graph, overhydration measurements using a body composition monitor, and calf BIS.
In this review, we will examine the principles of BIA, introduce various volume
status measurement methods, and identify the optimal method for patients
undergoing dialysis.
PMID- 29961309
TI - Hepatitis C virus infection in chronic kidney disease: paradigm shift in
management.
AB - Hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is associated
with increased liver-related morbidity and mortality rates, accelerated
progression to end-stage renal disease, and risk of cardiovascular events. CKD
patients with HCV infection require antiviral therapy. Pegylated interferon (peg
IFN) plus ribavirin was the standard of care for HCV-infected CKD patients before
the introduction of first-generation direct-acting antiviral (DAA) oral anti-HCV
agents. Peg-IFN-based treatment has a low virologic response rate and poor
compliance, resulting in a high dropout rate. Recently, several clinical trials
of all-DAA combination regimens have reported excellent antiviral efficacy and
few adverse drug reactions in HCV-infected patients with CKD. These positive
results have revolutionized the treatment of chronic HCV infection in this
population. In this review, we address the impact of chronic HCV infection in CKD
patients, and discuss their management using next-generation DAAs.
PMID- 29961310
TI - Transradial intervention as the first choice of treatment for ST elevation
myocardial infarction patients: editorial comment.
PMID- 29961311
TI - Avoiding "curiosity killed the cat": personalized surveillance in post-resection
colorectal cancer patients.
PMID- 29961312
TI - Evaluating LC-MS/MS To Measure Accumulation of Compounds within Bacteria.
AB - A general method for determining bacterial uptake of compounds independent of
antibacterial activity would be a valuable tool in antibacterial drug discovery.
LC-MS/MS assays have been described, but it has not been shown whether the data
can be used directly to inform medicinal chemistry. We describe the evaluation of
an LC-MS/MS assay measuring association of compounds with bacteria, using a set
of over a hundred compounds (inhibitors of NAD-dependent DNA ligase, LigA) for
which in vitro potency and antibacterial activity had been determined. All
compounds were active against an efflux-deficient strain of Escherichia coli with
reduced LigA activity ( E. coli ligA251 Delta tolC). Testing a single compound
concentration and incubation time, we found that, for equipotent compounds, LC
MS/MS values were not predictive of antibacterial activity. This indicates that
measured bacteria-associated compound was not necessarily exposed to the target
enzyme. Our data suggest that, while exclusion from bacteria is a major reason
for poor antibacterial activity of potent compounds, the distribution of compound
within the bacterial cell may also be a problem. The relative importance of these
factors is likely to vary from one chemical series to another. Our observations
provide directions for further study of this difficult issue.
PMID- 29961313
TI - A Zero Cross-Talk Ratiometric Two-Photon Probe for Imaging of Acid pH in Living
Cells and Tissues and Early Detection of Tumor in Mouse Model.
AB - Acid-base disorders disrupt proper cellular functions, which are associated with
diverse diseases. Development of highly sensitive pH probes being capable of
detecting and monitoring the minor changes of pH environment in living systems is
of considerable interest to diagnose disease as well as investigate biochemical
processes in vivo. We report herein two novel high-resolution ratiometric two
photon (TP) fluorescent probes, namely, PSIOH and PSIBOH derived from carbazole
oxazolidine pi-conjugated system for effective sensing and monitoring acid pH in
a biological system. Remarkably, PSIOH exhibited the largest emission shift of
~169 nm from 435 to 604 nm upon pH changing from basic to acidic with an ideal p
Ka value of 6.6 within a linear pH variation range of 6.2-7.0, which is highly
desirable for high-resolution tracking and imaging the minor fluctuation of pH in
live cells and tissues. PSIOH also exhibits high pH sensitivity, excellent
photostability, and reversibility as well as low cytotoxicity. More importantly,
this probe was successfully applied to (i) sense and visualize the pH alteration
in HeLa cells caused by various types of exogenous stimulation and (ii) detect
and differentiate cancer and tumors in liver tissues and a mouse model, realizing
its practical in vitro and in vivo applications.
PMID- 29961314
TI - GaCl3-Mediated "Inverted" Formal [3 + 2]-Cycloaddition of Donor-Acceptor
Cyclopropanes to Allylic Systems.
AB - A new process of "inverted" formal [3 + 2]-cycloaddition of donor-acceptor
cyclopropanes (DACs) to allylic systems to give polyfunctionalized cyclopentanes
has been developed. Unlike the classical version of formal [3 + 2]-cycloaddition,
a DAC acts in this process as a two-carbon synthon (1,2-zwitterionic reactivity
type), while an alkene acts as a three-carbon synthon. Tetramethylethylene,
allylbenzenes, homoallylbenzene, terminal and internal aliphatic alkenes, and
methylenecyclobutane were successfully used as alkenes. Furthermore, in order to
suppress annulation at the aromatic ring in 2-arylcyclopropane-1,1-dicarboxylates
and enhance the selectivity of the reaction with the allylic system of alkenes,
we suggested a new approach for managing the reactivity of DACs involving
substitution at both ortho positions of the aromatic ring. Multinuclear NMR
spectroscopy was used to study the structure of the 1,2-zwitterionic gallium
complexes generated and their properties and to examine the mechanisms of the
occurring reactions.
PMID- 29961315
TI - Can Path Integral Molecular Dynamics Make a Good Approximation for Vapor Pressure
Isotope Effects Prediction for Organic Solvents? A Comparison to ONIOM QM/MM and
QM Cluster Calculation.
AB - Isotopic fractionation of volatile organic compounds (VOCs), which are under
strict measures of control because of their potential harm to the environment and
humans, has an important ecological aspect, as the isotopic composition of
compounds may depend on the conditions in which such compounds are distributed in
Nature. Therefore, detailed knowledge on isotopic fractionation, not only
experimental but also based on theoretical models, is crucial to follow
conditions and pathways within which these contaminants are spread throughout the
ecosystems. In this work, we present carbon and, for the first time, bromine
vapor pressure isotope effect (VPIE) on the evaporation process from pure-phase
systems-dibromomethane and bromobenzene, the representatives of aliphatic and
aromatic brominated VOCs. We combine isotope effects measurements with their
theoretical prediction using three computational techniques, namely path integral
molecular dynamics, QM cluster, and hybrid ONIOM models. While evaporation of
both compounds resulted in normal bromine VPIEs, the difference in the direction
of carbon isotopic fractionation is observed for the aliphatic and aromatic
compounds, where VPIEs are inverse and normal, respectively. Even though
theoretical models tested here turned out to be insufficient for quantitative
agreement with the experimental values, cluster electronic structure
calculations, as well as two-layer ONIOM computations, provided better
reproduction of experimental trends.
PMID- 29961316
TI - Ultrahigh-Resolution Mass Spectrometry in Real Time: Atmospheric Pressure
Chemical Ionization Orbitrap Mass Spectrometry of Atmospheric Organic Aerosol.
AB - The accurate and precise mass spectrometric measurement of organic compounds in
atmospheric aerosol particles is a challenging task that requires analytical
developments and adaptations of existing techniques for the atmospheric
application. Here we describe the development and characterization of an
atmospheric pressure chemical ionization Orbitrap mass spectrometer (APCI
Orbitrap-MS) for the measurement of organic aerosol in real time. APCI is a well
known ionization technique, featuring minimal fragmentation and matrix
dependencies, and allows rapid alternation between the positive and negative
ionization mode. As a proof of principle, we report ambient organic aerosol
composition in real-time, with alternating ionization, high mass resolution ( R =
140 000) and accuracy (<2 ppm). The instrument was calibrated in the negative ion
mode using 3-methyl-1,2,3-butanetricarboxylic acid (MBTCA) model aerosol. We
obtain a detection limit of 1.3 ng/m3. Based on the performed calibration using
MBTCA particles, the ambient concentration of MBTCA in the particle phase
measured in an urban area in Mainz, Germany, ranged between 10 and 80 ng/m3. For
the first time, we apply a nontarget screening approach on real-time data,
showing molecular variability between ambient day- and nighttime aerosol
composition. The detected compounds were grouped in the night- and daytime and
analyzed by ultrahigh-resolution MS (UHRMS) visualization methods. Among several
prevalent biogenic secondary organic aerosol (BSOA) markers, 24 organic
mononitrates and one organic dinitrate were detected. We further estimate that,
on average, organic nitrates contribute to 5% and 14% of the measured particulate
organic aerosol at day and night, respectively.
PMID- 29961317
TI - Measurement of (Aptamer-Small Target) KD Using the Competition between
Fluorescently Labeled and Unlabeled Targets and the Detection of Fluorescence
Anisotropy.
AB - Registration of fluorescence anisotropy (FA) allows for characterizing the
interactions of ligands with aptamers and other receptors under homogeneous
conditions without reagent immobilization, prolonged incubations, and product
separation. We proposed an approach for aptamer affinity determination by FA
taking into account the difference in label fluorescence before and after
complexation. The detailed step by step scheme using a native and fluorescently
labeled ligand was described and justified in the paper. The scheme ensures the
exclusion of data with low reliability and establishes valid criteria for
selecting optimal concentrations of reagents (labeled ligand and aptamer) used in
the experiments. The approach was experimentally tested using ochratoxin A (OTA),
its fluorescein-labeled derivative (OTA-Flu), and the aptamer binding them. We
demonstrated that it allows minimizing the influence of fluorescence change to
accurately determine the dissociation constant. On the basis of FA registration,
the binding constants of the aptamer-OTA-Flu and the aptamer-OTA complexes were
found to be equal to 245 + 33 and 63 + 18 nM, respectively. The value for the
aptamer-OTA complexes was confirmed by the equilibrium dialysis technique. The
resulting constant was 80 +/- 9 nM. The versatility and methodological simplicity
of the proposed protocol, as well as the short implementation time, are why it
can be recommended as an effective tool for characterizing aptamer-ligand
complexes.
PMID- 29961318
TI - Palladium-Catalyzed Oxidative Three-Component Coupling of Anthranilamides with
Isocyanides and Arylboronic Acids: Access to 2,3-Disubstituted Quinazolinones.
AB - A novel palladium-catalyzed oxidative three-component coupling of easily
accessible N-substituted anthranilamides with isocyanides and arylboronic acids
is achieved. This protocol offers an alternative approach toward 2,3
disubstituted quinazolinones with a wide substrate scope and good functional
group tolerance.
PMID- 29961319
TI - Pinostrobin Exerts Neuroprotective Actions in Neurotoxin-Induced Parkinson's
Disease Models through Nrf2 Induction.
AB - The aim of the present study was to assess the neuroprotective effects of
pinostrobin (PSB), a dietary bioflavonoid, and its underlying mechanisms in
neurotoxin-induced Parkinson's disease (PD) models. First, PSB could attenuate 1
methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic
neurons and improve behavior deficiency in zebrafish, supporting its potential
neuroprotective actions in vivo. Next, PSB could decreased apoptosis and death in
the 1-methyl-4-phenylpyridinium (MPP+)-intoxicated SH-SY5Y cells, evidenced by
MTT, LDH, Annexin V-FITC/PI, and DNA fragmentation assay. PSB also blocked MPP+
induced apoptotic cascades, including loss of mitochondrial membrane potential,
activation of caspase 3, and reduced ratio of Bcl-2/Bax. In addition, PSB
suppressed MPP+-induced oxidative stress but increased antioxidant enzymes,
evidenced by decrease of reactive oxygen species generation and lipid
peroxidation and up-regulation of GSH-Px, SOD, CAT, GSH/GSSG, and NAD/NADH.
Further investigations showed that PSB significantly enhanced Nrf2 expression and
nuclear accumulation, improved ARE promoter activity and up-regulated expression
of HO-1 and GCLC. Furthermore, Nrf2 knockdown via specific Nrf2 siRNA abolished
PSB-induced antioxidative and antiapoptotic effects against MPP+ insults.
Interestingly, we then found that PSB promoted phosphorylation of PI3K/AKT and
ERK, and pharmacological inhibition of PI3K/AKT or ERK signaling diminished PSB
induced Nrf2/ARE activation and protective actions. In summary, PSB confers
neuroprotection against MPTP/MPP+-induced neurotoxicity in PD models. Promoting
activation of Nrf2/ARE signaling contributes to PSB-mediated antioxidative and
neuroprotective actions, which, in part, is mediated by PI3K/AKT and ERK.
PMID- 29961320
TI - Intramolecular Energy and Electron Transfers in Bodipy Naphthalenediimide Triads.
AB - Borondipyrromethene (BDP) naphthalenediimide (NDI) triads (BDP-NDI) and diiodo
BDP derivative (DiiodoBDP-NDI)) were synthesized to study the Forster resonance
energy transfer (FRET) and its impact on the triplet state formation and
dynamics. In these triads, diiodo-BDP and BDP are the energy donors and NDI is
the energy acceptor. Nanosecond transient absorption spectra of triads indicated
that triplet state is localized on NDI moiety, either by selective
photoexcitation of the Diiodo-BDP or NDI unit. The intersystem crossing (ISC) is
attributed to intramolecular heavy atom effect. The triplet state quantum yield
was found to be 54% with a lifetime of 38 MUs. However, no triplet state is
observed for BDP-NDI system either by exciting BDP or NDI unit. Thus, we
confirmed that charge recombination does not produce a triplet state.
Interestingly, DiiodoBDP-NDI can be used as broadband excitable (500-620 nm)
triplet photosensitizer, and high triplet-triplet annihilation (TTA) upconversion
quantum yield of PhiUC = 2.8% was observed with 9,10-bis(phenylethynyl)
anthracene (BPEA) as a triplet acceptor/emitter.
PMID- 29961321
TI - Amphiphilically Nanostructured Deep Eutectic Solvents.
AB - Deep eutectic solvents (DESs) are neoteric liquids produced by mixing a high
melting-point salt and a molecular hydrogen-bond donor. Amphiphilic (self
assembled) liquid nanostructure, which is key for many of the useful properties
of the related ionic liquid class, has not previously been experimentally
demonstrated in DESs. Here we show how amphiphilically nanostructured DESs can be
prepared using primary ammonium cations. The bulk structure of alkylammonium
bromide (alkyl = ethyl-, propyl-, and butyl) and glycerol DESs at a 1:2 mol ratio
is examined using neutron diffraction and empirical potential structure
refinement fitting. Analysis reveals cation alkyl chain association, which is the
signature of amphiphilic liquid nanostructure, in all systems, which becomes
better defined with increasing chain length. The ability to form amphiphilically
nanostructured DESs will enable the translation of ionic liquid properties
associated with liquid nanostructure to DESs.
PMID- 29961322
TI - Formulation of Long-Range Transport Rates through Molecular Bridges: From
Unfurling to Hopping.
AB - Weak fluctuations about the rigid equilibrium structure of ordered molecular
bridges drive charge transfer in donor-bridge-acceptor systems via quantum
unfurling, which differs from both hopping and ballistic transfer, yet static
disorder (low frequency motions) in the bridge is shown to induce a change of
mechanism from unfurling to hopping when local fluctuations along the molecular
bridge are uncorrelated. Remarkably, these two different transport mechanisms
manifest in similar charge-transfer rates, which are nearly independent of the
molecular bridge length. We propose an experimental test for distinguishing
unfurling from hopping in DNA models with different helix directionality. A
unified formulation explains the apparent similarity in the length dependence of
the transfer rate despite the difference in the underlying transport mechanisms.
PMID- 29961323
TI - Biomineralization of Calcium Phosphate and Calcium Carbonate within Iridescent
Chitosan/Iota-Carrageenan Multilayered Films.
AB - This work systematically explores the biomineralization of calcium phosphate
(CaP) and carbonate (CaCO3) within chitosan/iota-carrageenan multilayer films.
Multilayer films of chitosan and iota-carrageenan (up to 128-coupled layers) were
prepared on glass substrates by a layer-by-layer dip-coating technique. Cryo
scanning electron microscopy revealed dense interfaces between the chitosan and
iota-carrageenan layers with thicknesses in the range 250 and 350 nm in the
hydrated state, accounting for the iridescent nature of multilayer films when
wet. Immersion of the multilayered films in simulated body fluid or simulated
seawater at 25 degrees C resulted in the mineralization of CaP and CaCO3,
respectively, at the interfaces between the biopolymer layers and modified the
iridescence of the films. Lamellar scattering features in small-angle neutron
scattering measurements of the mineralized films provided evidence of the
localized mineralization. Further evidence of this was found through the lack of
change in the dynamic and static correlation lengths of the polymer networks
within the bulk phase of the chitosan and iota-carrageenan layers. CaP
mineralization occurred to a greater extent than CaCO3 mineralization within the
films, evidenced by the higher lamellar density and greater rigidity of the CaP
mineralized films. Results provide valuable new insights into CaP and CaCO3
biomineralization in biopolymer networks.
PMID- 29961324
TI - Visualizing miR-155 To Monitor Breast Tumorigenesis and Response to
Chemotherapeutic Drugs by a Self-Assembled Photoacoustic Nanoprobe.
AB - MicroRNA-155 (miR-155), which facilitates breast tumor growth and invasion by
promoting tumor cell proliferation and inhibiting cell apoptosis, is considered
an ideal early diagnostic and prognostic marker. Herein, we developed a self
assembled hybridization chain reaction (HCR)-based photoacoustic (PA) nanoprobe
for highly sensitive in situ monitoring of dynamic changes in miR-155 expression
during breast tumorigenesis and chemotherapy. The PA nanoprobes (Au-H1/PEG and Au
H2/PEG) were constructed by linking poly(ethylene glycol) (PEG) and two hairpin
DNA strands (H1 and H2, respectively) to the surface of gold nanoparticles
(AuNPs). In the presence of miR-155, the PA nanoprobes self-assembled into Au
aggregates via HCR between H1, H2, and miR-155. The decreased interparticle
distance in these aggregates enhanced the surface plasmon resonance (SPR) in the
AuNPs. Consequently, the absorption peak of the PA nanoprobes red-shifted, and
strong PA signals were generated. This strategy enabled the sensitive and
quantitative detection of miR-155 with a low detection limit of 0.25 nM. As a
result, PA signals of miR-155 were captured on the second day after tumor
inoculation when the solid tumor had not yet formed. Dynamic changes in miR-155
during tumor growth and chemotherapy were also monitored in real time to assess
the therapeutic effects via PA imaging. By virtue of these advantages, the PA
nanoprobes may provide a powerful platform for in situ detection of miR-155 and
thus real-time monitoring of tumorigenesis and drug response in breast cancer.
PMID- 29961325
TI - Arl2-Mediated Allosteric Release of Farnesylated KRas4B from Shuttling Factor
PDEdelta.
AB - Proper localization of Ras proteins at the plasma membrane (PM) is crucial for
their functions. To get to the PM, KRas4B and some other Ras family proteins bind
to the PDEdelta shuttling protein through their farnesylated hypervariable
regions (HVRs). The docking of their farnesyl (and to a lesser extent
geranylgeranyl) in the hydrophobic pocket of PDEdelta's stabilizes the
interaction. At the PM, guanosine 5'-triphosphate (GTP)-bound Arf-like protein 2
(Arl2) assists in the release of Ras from the PDEdelta. However, exactly how is
still unclear. Using all-atom molecular dynamics simulations, we unraveled the
detailed mechanism of Arl2-mediated release of KRas4B, the most abundant
oncogenic Ras isoform, from PDEdelta. We simulated ternary Arl2-PDEdelta-KRas4B
HVR complexes and observed that Arl2 binding weakens the PDEdelta-farnesylated
HVR interaction. Our detailed analysis showed that allosteric changes (involving
beta6 of PDEdelta and additional PDEdelta residues) compress the hydrophobic
PDEdelta pocket and push the HVR out. Mutating PDEdelta residues that mediate
allosteric changes in PDEdelta terminates the release process. Mutant Ras
proteins are enriched in human cancers, with currently no drugs in the clinics.
This mechanistic account may inspire efforts to develop drugs suppressing
oncogenic KRas4B release.
PMID- 29961326
TI - Adsorption of Maleic Acid Monomer on the Surface of Hydroxyapatite and TiO2: A
Pathway toward Biomaterial Composites.
AB - Poly(styrene- alt-maleic acid) adsorption on hydroxyapatite and TiO2 (rutile) was
studied using experimental techniques and complemented by ab initio simulations
of adsorption of a maleic acid segment as a subunit of the copolymer. Ab initio
calculations suggest that the maleic acid segment forms a strong covalent bonding
to the TiO2 and hydroxyapatite surfaces. If compared to vacuum, the presence of a
solvent significantly reduces the adsorption strength as the polarity of the
solvent increases. The results of first-principles calculations are confirmed by
the experimental measurements. We found that the adsorbed poly(styrene- alt
maleic acid) allowed efficient dispersion of rutile and formation of films by the
electrophoretic deposition. Moreover, rutile can be codispersed and codeposited
with hydroxyapatite to form composite films. The coatings showed an enhanced
corrosion protection of metallic implants in simulated body fluid solutions,
which opens new avenues for the synthesis, dispersion, and colloidal processing
of advanced composite materials for biomedical applications.
PMID- 29961327
TI - Sonochemically Assembled Photoluminescent Copper-Modified Graphene Oxide
Microspheres.
AB - A new accessible sonochemical assembly method is developed for the preparation of
photoluminescent oil-filled silica@CuS/Cu2O/CuO-graphene oxide (GO) microspheres
that emit light of green, yellow, and red colors. This method is based on the
ultrasonic emulsification of a biphasic mixture consisting of CuS/Cu2O/CuO
graphene oxide (GO) nanocomposites with poly(vinyl alcohol) (PVA) (aqueous phase)
and tetraethyl orthosilicate with sunflower oil (organic phase). CuS/Cu2O/CuO-GO
nanocomposites are composed of sonochemically formed three phases of copper:
covellite CuS (p-type semiconductor), cuprite Cu2O (Bloch p-type semiconductor),
and CuO (charge-transfer insulator). The photoluminescence properties of
microspheres result from H-bridging between PVA and CuS/Cu2O/CuO-GO
nanostructures, light absorption ability of Cu2O, and charge-transfer insulation
by CuO. Substitution of PVA by S-containing methylene blue quenches fluorescence
by enhanced dye adsorption on CuS/Cu2O/CuO-GO because of CuS and induced charge
transfer. Non-S-containing malachite green is in a nonionized form and tends to
be in the oil phase, prohibiting the charge transfer on CuS/Cu2O/CuO-GO.
PMID- 29961328
TI - Molecular Interactions behind the Self-Assembly and Microstructure of Mixed
Sterol Organogels.
AB - In this work, we have employed docking and atomistic molecular dynamics (MD)
simulations supported by complementary experiments using atomic force microscopy,
rheology, and spectroscopy to investigate the self-assembled structure of beta
sitosterol and gamma-oryzanol molecules into cylindrical tubules in a nonaqueous
solvent. Docking models of several phytosterols, including sitosterol, with
oryzanol and other sterol esters demonstrate that for systems to form tubules,
the phytosterol sterane group must be stacked in a wedge shape with the ester
sterane group and a hydrogen bond must form between the hydroxyl group of the
phytosterol and the carbonyl group of the ester. MD of the self-assembled
structure were initiated with the molecules in a roughly cylindrical
configuration, as suggested from previous experimental studies, and the
configurations were found to be stable during 50 ns simulations. We performed MD
simulations of two tubules in proximity to better understand the aggregation of
these fibrils and how the fibrils interact in order to stick together. We found
that an interfibril network of noncovalent bonds, in particular van der Waals and
pi-pi contacts, which is formed between the ferulic acid groups of oryzanol
through the hydroxyl, methoxy, and aromatic groups, is responsible for the
surface-to-surface interactions between fibrils; an observation supported by
molecular spectroscopy. We believe that these interactions are of primary
importance in creating a strong organogel network.
PMID- 29961329
TI - Multi-Valued Logic Circuits Based on Organic Anti-ambipolar Transistors.
AB - Multivalued logic circuits, which can handle more information than conventional
binary logic circuits, have attracted much attention as a promising way to
improve the data-processing capabilities of integrated circuits. In this study,
we developed a ternary inverter based on organic field-effect transistors (OFET)
as a potential component of high-performance and flexible integrated circuits.
Key elements are anti-ambipolar and n-type OFETs connected in series. First, we
demonstrate an organic ternary inverter that exhibits three distinct logic
states. Second, the operating voltage was greatly reduced by taking advantage of
an Al2O3 gate dielectric. Finally, the operating voltage was finely tuned by the
designing of the device geometry. These results are achievable owing to the
flexible controllability of the device configuration, suggesting that the organic
ternary inverter plays an important role with regard to high-performance organic
integrated circuits.
PMID- 29961331
TI - Solvent-Free Enantioselective Michael Reactions Catalyzed by a Calixarene-Based
Primary Amine Thiourea.
AB - An upper-rim functionalized calix[4]arene-based thiourea installed onto the ( R,
R)-1,2-cyclohexanediamine scaffold was synthesized with a view to investigate its
catalytic ability in enantioselective Michael additions. The reactions were found
to conveniently proceed under solvent-free conditions, observing good to high
enantioselectivities. From this preliminary study, the calix[4]arene unit is
likely to play a role in affecting the conversion and to a lesser extent to the
stereochemical outcome of the reactions through van der Waals contacts and C
H...pi interactions with the substrates.
PMID- 29961330
TI - Activation Energy of Organic Cation Rotation in CH3NH3PbI3 and CD3NH3PbI3: Quasi
Elastic Neutron Scattering Measurements and First-Principles Analysis Including
Nuclear Quantum Effects.
AB - The motion of CH3NH3+ cations in the low-temperature phase of the promising
photovoltaic material methylammonium lead triiodide (CH3NH3PbI3) is investigated
experimentally as well as theoretically, with a particular focus on the
activation energy. Inelastic and quasi-elastic neutron scattering measurements
reveal an activation energy of ~48 meV. Through a combination of experiments and
first-principles calculations, we attribute this activation energy to the
relative rotation of CH3 against an NH3 group that stays bound to the inorganic
cage. The inclusion of nuclear quantum effects through path integral molecular
dynamics gives an activation energy of ~42 meV, in good agreement with the
neutron scattering experiments. For deuterated samples (CD3NH3PbI3), both theory
and experiment observe a higher activation energy for the rotation of CD3 against
NH3, which results from the smaller nuclear quantum effects in CD3. The rotation
of the NH3 group, which is bound to the inorganic cage via strong hydrogen
bonding, is unlikely to occur at low temperatures due to its high energy barrier
of ~120 meV.
PMID- 29961332
TI - Sodium Butyrate Ameliorates High-Fat-Diet-Induced Non-alcoholic Fatty Liver
Disease through Peroxisome Proliferator-Activated Receptor alpha-Mediated
Activation of beta Oxidation and Suppression of Inflammation.
AB - Peroxisome proliferator-activated receptor alpha (PPARalpha) plays a protective
role against non-alcoholic fatty liver disease (NAFLD). Sodium butyrate (NaB) has
been shown to alleviate NAFLD, yet whether and how PPARalpha is involved in the
action of NaB remains elusive. In this study, NaB administration alleviated high
fat-diet-induced NAFLD in adult rats, with a decrease of hepatic triglyceride
content from 108.18 +/- 5.77 to 81.34 +/- 7.94 MUg/mg ( p < 0.05), which was
associated with a significant activation of PPARalpha. Nuclear factor kappa-light
chain-enhancer of activated B cell (NF-kappaB)-mediated nucleotide-binding domain
like receptor protein 3 signaling and pro-inflammatory cytokine release were
diminished by NaB treatment. NaB-induced PPARalpha upregulation coincided with a
reduced protein content of histone deacetylase 1 and promoted histone H3 acetyl
K9 (H3K9Ac) modification on the promoter of PPARalpha, whereas NaB-induced
suppression of inflammation was linked to significantly increased PPARalpha
binding with p-p65. NaB acts as a histone deacetylase inhibitor to upregulate
PPARalpha expression with enhanced H3K9Ac modification on it promoter. NaB
induced PPARalpha activation stimulates fatty acid beta oxidation and inhibits NF
kappaB-mediated inflammation pathways via protein-protein interaction, thus
contributing to amelioration of high-fat-diet-induced NAFLD in adult rats.
PMID- 29961333
TI - Multisensor Imaging-From Sample Preparation to Integrated Multimodal
Interpretation of LA-ICPMS and MALDI MS Imaging Data.
AB - Laterally resolved chemical analysis (chemical imaging) has increasingly
attracted attention in the Life Sciences during the past years. While some
developments have provided improvements in lateral resolution and speed of
analysis, there is a trend toward the combination of two or more analysis
techniques, so-called multisensor imaging, for providing deeper information into
the biochemical processes within one sample. In this work, a human malignant
pleural mesothelioma sample from a patient treated with cisplatin as a cytostatic
agent has been analyzed using laser ablation inductively coupled plasma mass
spectrometry (LA-ICPMS) and matrix-assisted laser desorption/ionization mass
spectrometry (MALDI MS). While LA-ICPMS was able to provide quantitative
information on the platinum distribution along with the distribution of other
elemental analytes in the tissue sample, MALDI MS could reveal full information
on lipid distributions, as both modes of polarity, negative and positive, were
used for measurements. Tandem MS experiments verified the occurrence of distinct
lipid classes. All imaging analyses were performed using a lateral resolution of
40 MUm, providing information with excellent depth of details. By analyzing the
very same tissue section, it was possible to perfectly correlate the obtained
analyte distribution information in an evaluation approach comprising LA-ICPMS
and MALDI MS data. Correlations between platinum, phosphorus, and lipid
distributions were found by the use of advanced statistics. The present proof-of
principle study demonstrates the benefit of data combination for outcomes beyond
one method imaging modality and highlights the value of advanced chemical imaging
in the Life Sciences.
PMID- 29961334
TI - Surface Modification of SiC Powder with Sodium Humate: Adsorption Kinetics,
Equilibrium, and Mechanism.
AB - Highly dispersible SiC powder was prepared using sodium humate as a modifier. The
results showed that the zeta-potential absolute value of the modified SiC powder
increased from 13.1 to 38.7 mV when the adsorption capacity of sodium humate on
the SiC surface was 2.368 mg/g. The slurry with a maximum solid content of 65 vol
% was obtained using the modified SiC powder, and the minimum viscosity value was
0.322 Pa s at a solid content of 50 vol %. The adsorption kinetics equation of
sodium humate on the SiC surface is t/ q t = 0.6253 t + 11.0472, which is in
accordance with the pseudo-second-order kinetics model. In addition, the isotherm
equation, ln qe = 0.461 ln Ce - 0.334, agrees with the Freundlich model. The
adsorption energy of sodium humate on the SiC surface was 0.8280 kJ/mol,
indicating that the adsorption type was physical adsorption.
PMID- 29961335
TI - Dearomative Cascade Photocatalysis: Divergent Synthesis through Catalyst
Selective Energy Transfer.
AB - The discovery and application of dearomative cascade photocatalysis as a strategy
in complex molecule synthesis is described. Visible-light-absorbing
photosensitizers were used to (sequentially) activate a 1-naphthol derived arene
precursor to divergently form two different polycyclic molecular scaffolds
through catalyst selective energy transfer.
PMID- 29961336
TI - Giant Lipid Vesicle Formation Using Vapor-Deposited Charged Porous Polymers.
AB - In this study, we prepare giant lipid vesicles using vapor-deposited charged
microporous poly(methacrylic acid- co-ethylene glycol diacrylate) polymer
membranes with different morphologies and thicknesses. Our results suggest that
vesicle formation is favored by thinner, more structured porous hydrogel
substrates. Electrostatic interactions between the polymer and the lipid head
groups affect vesicle yield and size distribution. Repulsive electrostatic
interactions between the hydrogel and the lipid head groups promote vesicle
formation; attractive electrostatic interactions suppress vesicle formation.
Ionic strength and sugar concentration are also major parameters affecting the
yield and size of giant vesicles. The presence of both ions and sugars in the
hydration buffer results in increased vesicle yields. These results indicate that
lipid-polymer interactions and osmotic effects in addition to the substrate
morphology and surface charge are key factors affecting vesicle formation. Our
data suggest that surface chemistry should be designed to tune electrostatic
interactions with the lipid mixture of interest to promote vesicle formation.
This vapor-deposited hydrogel fabrication technique offers tunability over the
physicochemical properties of the hydrogel substrate for the production of giant
vesicles with different sizes and compositions.
PMID- 29961337
TI - Evolution strategy of ROS1 kinase inhibitors for use in cancer therapy.
AB - The abnormal expression of c-ros oncogene1 receptor tyrosine kinase (ROS1) has
been identified as clinically actionable oncogenic driver in non-small-cell lung
cancer. Since crizotinib was approved by the US FDA for the treatment of advanced
ROS1-positive non-small-cell lung cancer, ROS1 kinase has become a promising
therapeutic target. Under the guidance of some advanced computer-assisted
technologies, such as structure-based drug design, homology modeling and
lipophilic efficiency parameters, several potent and selective inhibitors against
wild-type and mutant ROS1 were designed and synthesized. In this article, we will
review a series of scaffolds targeting ROS1 kinase from the hit-to-drug evolution
strategies of their representative compounds and it is hoped that these design
strategies would facilitate medicinal chemists to optimize the process of drug
design.
PMID- 29961338
TI - Effect of artificial cell miniaturization on urea degradation by immobilized E.
coli DH5alpha (pKAU17).
AB - Second generation E. coli DH5alpha (pKAU17) was successfully encapsulated by
means of atomization (MA), inkjet printing (MI) and double-encapsulation (DDMI)
for the purpose of urea degradation in a simulated uremic medium at 37 degrees
C. Experimentally determined values of the effectiveness factor are 0.83, 0.28
and 0.34 for the MI, MA and DDMI capsules, respectively, suggesting that the
catalytic activity of the E. coli DH5alpha (pKAU17) immobilized in MI capsule (d
= 52 MUm +/- 2.7 MUm) is significantly less diffusion-limited than in the case of
the MA (d = 1558 MUm +/- 125 MUm) and DDMI (d = 1370 MUm +/- 60 MUm) bio
encapsulation schemes at the 98.3% CI. The proposed novel double encapsulation
biofabrication method for alginate-based microspheres, characterized by lower
membrane degradation rates due to secondary containment is recommended compared
to the standard atomization scheme currently adopted across immobilization-based
therapeutic scenarios. A Fickian-based mechanism is proposed with simulations
mimicking urea degradation for a single capsule for the atomization and the
inkjet schemes.
PMID- 29961339
TI - A novel method for determination of the filling level in the feed frame of a
rotary tablet press.
AB - AIM: The aim of this study was to investigate whether the filling level within
the feed frame of a rotary tablet press can be quantified by laser triangulation
combined with the angle recognition of one paddle wheel via rotary encoder.
SIGNIFICANCE: Rotary tablet press feed frames are supposed to assure a uniform
die filling and, thus, to guarantee the weight and content uniformity of the
resulting tablets. Therefore, a constant bulk availability and flow within the
feed frame is crucial and has to be ensured by the feed frame design and the
operating conditions. So far, there is no instrument available to monitor the
bulk filling level or the bulk distribution within feed frames. METHODS: Calcium
phosphate dihydrate was used as model powder. The powder surface level was
determined via laser triangulation and the angle position of the paddle wheel was
monitored via incremental rotary encoder. The data of both parameters was
acquired synchronously and evaluated by in-house written software. RESULTS:
Different powder masses led to significantly different filling level signals. The
experiments showed a high reproducibility of the determined filling levels.
Furthermore, an influence of the rotational speed on the powder distribution was
observed. CONCLUSIONS: The developed instrument may be used for quantification of
the volumetric filling level within rotary tablet press feed frames. It may
either be used to better understand the powder behavior within feed frames or for
improvement of the die filling process by implementing the device into a feedback
loop.
PMID- 29961340
TI - Age and health-related quality of life, general self-efficacy, and functional
level 12 months following dysvascular major lower limb amputation: a prospective
longitudinal study.
AB - AIM: This study investigates the effect of time and age on health-related quality
of life, general self-efficacy, and functional level 12 months following
dysvascular major lower limb amputation (LLA). METHODS: A prospective cohort
study design with assessments at baseline and follow-up 3, 6, and 12 months post
amputation. Data were collected via in-person interviews using Short Form 36, the
General Self-efficacy scale and Barthel Index 100. Out of a consecutive sample of
103 patients having dysvascular major LLA (tibia, knee, or femoral), 38 patients
completed the study. Outcome at follow-up was compared with baseline and analyzed
in age groups. RESULTS: All SF36 subscale scores were below population norms at
baseline. At 12 months, two out of eight scores-physical function and role
physical-had not improved. Different patterns of change over the 12 months were
detected among the subscales, and psychosocial problems persisted and fluctuated
throughout the 12 months in all age groups. Large differences were identified
between age groups in physical function with the loss of physical function almost
solely evident among the oldest (aged 75+ years) patients. CONCLUSIONS: Special
attention should be given to the oldest patients need for rehabilitation so that
they gain higher quality of life. Implications for rehabilitation Psychosocial
problems persist and fluctuate throughout the first 12 months after major LLAs in
all age groups and rehabilitation services should include psychosocial support
throughout the first year to all patients independent of age. Waiting for an
unnecessarily long period of time for a prosthesis can negatively impact both
physical and psychosocial aspects of health-related QOL, and interventions to
reduce waiting time are warranted. Differences between age groups in functional
level after 12 months exist, with the loss of function almost solely evident
among the oldest patients (aged 75+ years). A special focus should be given to
the oldest patients' need of everyday rehabilitation to regain basic physical
functions.
PMID- 29961341
TI - Resuming Publication of an Established Journal.
PMID- 29961342
TI - The effects of cigarette smoking and smoking cessation on high-density
lipoprotein functions: implications for coronary artery disease.
AB - Background Smoking cessation was associated with improved prognosis of coronary
artery disease. This study was designed to investigate the effect of smoking
cessation on high-density lipoprotein functionality in coronary artery disease
patients. Methods In this prospective, randomized and parallel controlled study,
coronary artery disease smokers ( n = 28) and healthy smokers ( n = 30) were
divided into smoking cessation group and continuous smoking group, respectively.
Blood samples were collected before and after three-month smoking cessation.
Plasma high-density lipoprotein was isolated by density gradient centrifugation.
The ability of high-density lipoprotein against copper-induced oxidation of
lipoprotein was determined to evaluate the antioxidative property of high-density
lipoprotein, and the macrophage migration inhibited by high-density lipoprotein
was tested to identify the antichemotactic property of high-density lipoprotein.
High-density lipoprotein-induced macrophage cholesterol efflux was measured by
fluorescence spectrometry using NBD cholesterol analogue. Healthy non-smoking
volunteers were enrolled as the baseline control. Results The baseline
antioxidative, antichemotactic ability of high-density lipoprotein and high
density lipoprotein-induced cellular cholesterol efflux in coronary artery
disease smokers and healthy smokers were significantly attenuated when compared
with those in healthy non-smokers. After three-month smoking cessation, both the
antioxidative ability and antichemotactic ability of high-density lipoprotein
were improved significantly in coronary artery disease smokers. However, high
density lipoprotein-induced cellular cholesterol efflux was not increased by
smoking cessation. In in vitro experiments, carbon monoxide reduced the
antioxidative ability and nicotine enhanced the antichemotactic ability of high
density lipoprotein. Conclusions Smoking cessation is an effective measure to
improve high-density lipoprotein functions in coronary artery disease smokers.
Our study re-emphasizes the importance of smoking cessation in the secondary
prevention of coronary artery disease.
PMID- 29961343
TI - Release promoter-based systematically designed nanocomposite(s): a novel approach
for site-specific delivery of tumor-associated antigen(s) (TAAs).
AB - The aim of present approach was to design and develop mannose functionalized
reverse polymeric nanocomposite(s) system based on release promoter (MRPRPNs).
Thus, the composition of the present formulation was optimized by employing the
systematic design of experiments (DoE) for screening and optimization using L8
Array Taguchi and 3-level-3-factor Box-Behnken Design (BBD). Further, the
developed formulation was observed for its preferential internalization by
professional antigen presenting cells (macrophages/dendritic cells) and prompt
release of loaded antigen in a pH-dependent manner. The optimized formulation was
also extensively characterized for average hydrodynamic diameter, surface
potential, poly dispersity index of reverse polymeric nanocomposite(s) which were
recoded to be 189.4 +/- 8.52 nm, 0.111 +/- 0.024, -23.4 +/- 2.0 mV, respectively;
while percentage entrapment efficiency of OVA in MRPRPNs to be 60.17 +/- 2.41%.
The release pattern of OVA from MRPRPNs was consistent at pH 7.4. However, at
acidic pH (~5.5) where in protons (H+) are in-filtered into the core of MRPRPNs
thereby generating the pressure, resultantly causing and creating the pores or
disruption of the system thus allowed a prompt release (~60-70%) of encapsulated
OVA from interior to outer milieu within 1 h. MRPRPNs were preferentially
internalized through receptor-mediated endocytosis and released the loaded OVA
into the cytosol of RAW 264.7 cells. From the above findings, it can be concluded
that reverse polymeric system could significantly be loaded with
immunobioactive(s) and could potentially deliver the contents at the specific
site for the better therapeutic outcome.
PMID- 29961344
TI - Emulgel based on amphotericin B and bacuri butter (Platonia insignis Mart.) for
the treatment of cutaneous leishmaniasis: characterization and in vitro assays.
AB - OBJECTIVE: This work aimed to develop and characterize a topical emulgel of
amphotericin B (AmB) with bacuri butter (Platonia insignis Mart.) and evaluate
its antileishmanial activity using in vitro assays. SIGNIFICANCE: Leishmaniasis
is considered an infectious disease, with high incidence and capacity to produce
deformities. The first-line treatment recommended by WHO, with pentavalent
antimonials, is aggressive and very toxic. Therefore, the development of topical
treatments can emerge as a promising and less offensive alternative. METHODS: The
developed formulations were evaluated for organoleptic characteristics,
centrifugation resistance, globule size, pH, electrical conductivity, viscosity,
spreadability, drug content, preliminary stability, in vitro release profile,
evaluation of antileishmanial activity using promastigotes forms of Leishmania
major as infecting agents, macrophage cytotoxicity and selectivity index (IS).
RESULTS: Formulated emulsions presented organoleptic characteristics compatible
with its constituents; pH values were suitable for topical application, ranging
from 4.73 to 5.02; introduced non-Newtonian shear thinning system; drug content
was within the established standards, and the most suitable kinetic model of
release was the first order. Regarding the in vitro assays, formulations
containing both 1% and 3% of AmB presented similar outcomes, indicating a
synergism between the bacuri butter and the drug, possibly showing a reduction on
cytotoxicity to host cells. CONCLUSIONS: It was concluded that the formulations
developed showed promising antileishmanial action and high potential for topical
use.
PMID- 29961345
TI - Dual effects include antioxidant and pro-oxidation of ascorbic acid on the redox
properties of bovine hemoglobin.
AB - The oxidation reactions have become the main obstacle of development of bovine
hemoglobin-derivates products. Herein, the effects of vitamin C (Vc), a easily
available natural antioxidant reagent, on the redox reaction of bovine hemoglobin
were systematically investigated through methemoglobin (MetHb) formation and
spectrophotometric analysis and oxygen affinity monitoring of hemoglobin. The
results showed that Vc presented antioxidant effects in the initial stage of
reaction and then could accelerated the MetHb content increasing by production of
hydrogen peroxide, which can be indirectly characterized by the formation of
choleglobin in the following side reactions. The dual effects of Vc include
antioxidant and pro-oxidant effects could be confirmed by the spectrophotometric
spectrums analysis in this research. The results of this research supplied the
novel insight into understanding of redox properties of bovine hemoglobin and
also revealed the main obstacle in exploration of Vc application in the future
development of bovine hemoglobin-derivates products.
PMID- 29961346
TI - Experiences of participating in a client-centred ADL intervention after stroke.
AB - BACKGROUND: This qualitative study was conducted in the context of a client
centred activities of daily living (CADL) intervention aiming to enable agency in
daily activities and participation in everyday life after stroke. The
intervention was based on the principles of client-centred occupational therapy
and then further developed based on empirical research findings. OBJECTIVE: To
identify what from the clients' perspective characterises the lived experience
and meaning of participating in a CADL intervention after stroke. METHODS: The
study included 10 persons with stroke who received the intervention and who were
able to communicate their experience of participating. Data were collected
through two interviews, after the initiation and after the end of the
intervention. The analysis was performed using an empirical phenomenological
psychological method. RESULTS: The overall characteristic of the meaning of
participating in the intervention was transparency, which was expressed in the
participants' experiences of being able to see and follow their own
rehabilitation process. An awareness and understanding of their own situation
enabled the participants to be actively involved in their rehabilitation.
CONCLUSION: The intervention contributed to transparency, which appeared to
enable and support the client's sense of ownership of daily activities and
rehabilitation after stroke. Implications for rehabiliation A client-centred
activities of daily living intervention seems to contribute to transparency,
where persons with stroke can discover and understand their new ability and
situation after stroke. A client-centred rehabilitation situation seems to enable
clients to actively engage in their own rehabilitation process. Inviting clients
to participate in goal-setting seems to be important in order to create the
experience of transparency. Creating continuity in the therapeutic alliance seems
to be important in order for the clients to feel trust and experience agency in
everyday life.
PMID- 29961347
TI - TREM-1 Neutrophil Activation Pathway Is Suppressed in Eosinophilic Nasal Polyps.
AB - Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by
type 2 helper T-cell-skewed immune profiles, but the state of the neutrophil
activation signaling pathway in CRSwNP is unknown. The purpose of this study was
to examine neutrophil activation pathways in the pathogenesis of CRSwNP. Methods
Institutional review board approved the study in which tissue proteomes were
compared between control (inferior turbinate) and CRSwNP (nasal polyps) (n =
10/group) using an aptamer-based proteomic array and confirmed by whole
transcriptomic analysis. Protein expression was analyzed using Student's t test
and Benjamini-Hochberg procedures followed by the application of Ingenuity
Pathway, MetaCore, and Genemania bioinformatics analyses. Results All the
patients with CRSwNP (n = 10) had eosinophilic nasal polyps. Compared with
controls, proteins associated with the triggering receptor expressed on myeloid
cells 1 (TREM-1) neutrophil activation signaling pathway such as Calcineurin B,
zeta chain-associated protein kinase of 70 kD (ZAP70), 14-3-3 protein theta, 14-3
3 protein zeta/delta, protein kinase C delta type (PKC-D), Interleukin (IL)-17B,
IL-17B receptor, IL-23, and IL-1B were significantly decreased in CRSwNP (fold
change [FC] = -1.60, P = .003; FC = -1.85, P = .040; FC = -1.26, P < .001; FC =
1.05, P = .008; and FC = -1.31, P = .004; FC = -1.22, P < .001; FC = -1.09, P =
.022; FC = -1.25, P < .001; and FC = -1.31, P = .014; respectively). In contrast,
tissue eosinophil count ( P < .001) and eosinophil-associated proteins such as C
C motif chemokine 17, periostin, and galectin 10 were all significantly increased
in CRSwNP (FC = 1.56, P = .009; FC = 3.95, P < .001; and FC = 2.44, P < .001;
respectively). Furthermore, the FC of the studied proteins' expression
significantly and positively correlated with FC of their mRNA expression ( P =
.001, r = .75). Conclusions TREM-1-associated neutrophilic signaling pathway
proteins are significantly suppressed in eosinophilic CRSwNP.
PMID- 29961348
TI - A path analysis model for grooming performance in stroke patients.
AB - PURPOSE: The aim of this study was to clarify the relationships between various
types of functions and grooming performance and describe their hierarchical
structure in survivors of stroke. METHOD: This was a retrospective observational
study on 75 individuals with first stroke. A hypothetical path model, created
based on previous studies, was examined for goodness of fit between the data and
the model using path analysis. We hypothesized that in survivors of stroke,
grooming performance is influenced by age, motor and sensory functions of the
affected limbs, trunk function, grip and knee extensor strength, visuospatial
perception, intellectual function, motivation, affected and unaffected upper limb
function, and balance. RESULTS: A revised path model was created that achieved
goodness-of-fit index criteria. Balance, affected and unaffected upper limb
function, and motivation were found to have a direct effect and balance and
unaffected upper limb function were found to have especially stronger effect on
grooming performance. The order of the standardized total effects of each
function was as follows: balance, unaffected upper limb function, motivation, and
affected lower limb function. CONCLUSIONS: Our results suggest that interventions
targeting balance and unaffected upper limb function could be effective in
rehabilitation to improve grooming performance in survivors of stroke.
Implications for rehabilitation Balance and unaffected upper limb function have a
strong effect on grooming independence in survivors of stroke. Balance is most
influenced by affected lower limb function, and unaffected upper limb function is
equally influenced by balance, visuospatial perception, and grip strength.
Interventions targeting balance and unaffected upper limb function can improve
grooming performance in survivors of stroke.
PMID- 29961349
TI - Case Report of Pink Papules and a Single Nodule: What Could They Have in Common?
PMID- 29961350
TI - Systematic review of the clinical development of group B streptococcus serotype
specific capsular polysaccharide-based vaccines.
AB - INTRODUCTION: Vaccination against group B Streptococcus (GBS) during pregnancy
could provide protection against disease in the mother, fetus, and newborn.
Immunity through transplacental acquired antibodies in the newborns could persist
through early infancy, reducing the risk of early-onset (<7 days age) and late
onset (7-89 days age) disease. We conducted a systematic review of clinical
trials on GBS capsular polysaccharide (CPS) vaccine to assess its safety and
immunogenicity in pregnant and nonpregnant adults. Areas covered: We searched
literature databases PubMed (Medline), Scopus, and the Cochrane library and
identified 25 unique records on GBS CPS vaccines with or without conjugant
protein. Expert commentary: GBS vaccines were well tolerated, with mild local
reactogenicity being the main solicited adverse event and no difference in
reporting of other serious adverse events compared to placebo recipients. CPS
vaccines conjugated to immunogenic proteins induced >=fourfold increase of
serotype-specific antibodies with high longevity (1-2 years); and capable of
promoting homotypic GBS opsonophagocytic killing. Feto-maternal transplacental
antibody ratio of serotype-specific IgG ranged between 0.49 and 0.81. The
clinical relevance of these immunogenicity studies, however, need to be weighed
against a correlate of protection against invasive GBS disease in infants, which
is yet to be established using a universally accepted standardized assay.
PMID- 29961351
TI - Oxygen uptake on-kinetics before and after aerobic exercise training in
individuals with traumatic brain injury.
AB - OBJECTIVE: The high prevalence of fatigue among persons with traumatic brain
injury (TBI) may be related to poor cardiorespiratory fitness observed in this
population. Oxygen uptake on-kinetics is a method of assessing cardiorespiratory
fitness and may be used to examine performance fatigability (decline in
performance during a given activity) in persons with TBI. PURPOSE: To examine the
effect of aerobic exercise training on oxygen uptake on-kinetics during treadmill
walking in individuals with TBI. METHODS: Seven ambulatory adults with chronic
non-penetrating TBI performed short moderate-intensity (3-6 metabolic
equivalents) walking bouts on a treadmill, prior to and following an aerobic
exercise training program (clinicaltrials.gov: NCT01294332). The 12-week training
program consisted of vigorous-intensity exercise on a treadmill for 30 min, 3
times a week. Breath-by-breath pulmonary gas exchange was measured throughout the
bouts, and oxygen uptake on-kinetics described the time taken to achieve a steady
state response. RESULTS: Faster oxygen uptake on-kinetics was observed after
exercise training, for both the absolute and relative intensity as pre-training.
CONCLUSIONS: Faster oxygen uptake on-kinetics following aerobic exercise training
suggests an attenuated decline in physical performance during a standardized
walking bout and improved performance fatigability in these individuals with TBI.
Implications for rehabilitation Severe fatigue is a common complaint among
persons with traumatic brain injury (TBI). Oxygen uptake on-kinetics may be used
as an objective physiological measure of performance fatigability in persons with
TBI. Faster oxygen uptake on-kinetics following aerobic exercise training
suggests improved performance fatigability in these individuals with TBI. Aerobic
exercise training appeared beneficial for reducing performance fatigability and
may be considered as part of the rehabilitative strategy for those living with
TBI.
PMID- 29961352
TI - Do bismuth complexes hold promise as antileishmanial drugs?
AB - Even after 70 years, pentavalent antimonials sodium stibogluconate and meglumine
antimoniate remain the most important and cost-effective antileishmanial drugs.
However, the drugs cannot be delivered orally and treatment involves
intravascular or intramuscular injections for 28 days under strict medical
monitoring due to the toxicity of Sb(III). The main alternatives, amphotericin B,
pentamidine and miltefosine, are expensive and not without their own problems.
Bismuth sits below antimony in the periodic table and is considered to be
relatively nontoxic to humans while being capable of providing powerful
antimicrobial activity. This review describes recent efforts into developing
antileishmanial Bi(III) and Bi(V) drugs, which may resemble Sb analogs in effect
and mode-of-action while providing lower mammalian cell toxicity and
opportunities of oral delivery. Within the last 10 years, various studies
concerning bismuth-based compounds as potential antileishmanial agents have been
published. This review seeks to summarize the relevant studies and draw a
conclusion as to whether bismuth complexes have the potential to be effective
drugs.
PMID- 29961353
TI - Effectiveness and safety of dual influenza and pneumococcal vaccination versus
separate administration or no vaccination in older adults: a meta-analysis.
AB - BACKGROUND: The advantages of dual pneumococcal and influenza vaccination in
older adults have not been clarified and controversy remains regarding their
optimal use. METHODS: This meta-analysis was conducted on 25 January 2018 using
PubMed, the Cochrane Library, and Embase databases. Seventeen studies were
selected ultimately for meta-analysis using a multi-step approach by two separate
authors. Primary outcomes were pneumonia, pneumococcal pneumonia, influenza,
hospitalization, and all-cause mortality rates, and the secondary outcome was
adverse effects (AEs). RESULTS: The additive preventive effects of dual influenza
and pneumococcal vaccination versus influenza vaccination alone for pneumonia and
death were 15% (95% confidence interval [CI]: 4-24%) and 19% (95% CI: 6-30%),
respectively. Compared with pneumococcal vaccination alone, dual influenza and
pneumococcal vaccination resulted in a 24% (95% CI: 16-31%) reduction in
pneumonia and a 28% (95% CI: 13-40%) reduction in death. Compared with placebo or
no vaccination, the effectiveness of dual vaccination was 29% (95% CI: 14-42%)
for pneumonia, 38% (95% CI: 25-49%) for death, 35% (95% CI: 22-46%) for
influenza, and 18% (95% CI: 6-29%) for hospitalization. Both vaccines showed
acceptable safety profiles and AEs were mild or moderate. CONCLUSION: Our
findings highlight the importance of concomitant influenza and pneumococcal
vaccination in older adults.
PMID- 29961354
TI - Between SET and ASP: balancing the scales of student evaluation of teaching (SET)
and teachers' assessments of student performance (ASP) for medical school
education in psychiatry.
AB - OBJECTIVES:: We explore the relative roles of student evaluation of teaching
(SET) and teachers' assessment of student performance (ASP) in medical school
education in psychiatry. CONCLUSIONS:: We conclude that SET and ASP need to be
better researched as outcome measures, and input from both processes needs to be
balanced in evaluating psychiatric medical education.
PMID- 29961355
TI - Activity of silver nanoparticles on prokaryotic cells and Bothrops jararacussu
snake venom.
AB - Nanoparticle-conjugated venom-toxins of venomous animals and its therapeutic
efficacy against emerging or neglecting diseases is a promising strategy. In this
study, silver nanoparticles (AgNPs ~50 nm, 0.081 mg mL-1) were studied against
the neuromuscular blockade, myotoxic effects induced by Bothrops jararacussu
venom (60 ug mL-1) and also against prokaryotic cells. The neurotoxicity was
evaluated on ex vivo mouse phrenic nerve-diaphragm using traditional myographic
technique, able to obtain functional contractile responses and to check the
neurotransmission. The myotoxicity on mammalian cells was evaluated in muscles
resulting from pharmacological assays using routine histological techniques and
light microscopy. The toxicity to prokaryotic cells was evaluated on Salmonella
typhimurium TA100 without metabolic activation. The in vitro preincubation model
between AgNPs and venom was enough to abolish toxic effects of B. jararacussu
venom, but mammalian cells were highly sensitive to AgNPs more than prokaryotic
cells, by acting as dose-independently and dose-dependently parameters,
respectively. These results allowed us to conclude that AgNPs showed promising
activity as antivenom agent but for its safer use, the toxicity should be
evaluated on experimental animals.
PMID- 29961356
TI - Exploring the dynamics of ART adherence in the context of a mindfulness
instruction intervention among youth living with HIV in Baltimore, Maryland.
AB - Youth living with HIV have sub-optimal rates of adherence to antiretroviral
therapy (ART). Mindfulness instruction interventions have shown promise for
improving medication adherence, but the effects and mechanisms of these
interventions are still being explored among people living with HIV, including
youth. In the context of a randomized controlled trial of the efficacy of a
Mindfulness-Based Stress Reduction (MBSR) program on ART adherence and viral
suppression among youth living with HIV, we conducted 44 iterative, semi
structured, in-depth interviews with 20 study participants (13-24 years)
recruited from clinics at two academic centers in Baltimore, Maryland. Interviews
explored the social context and psychosocial dynamics of ART adherence in the
context of the MBSR intervention, compared with those in a control arm. We
employed thematic content analysis to systematically code and synthesize textual
interview data. Participants' challenges with ART adherence were often situated
within an ongoing process of working to manage HIV as a stigmatized, chronic
condition in addition to other intersecting social stigmas, inequalities, and
stressors. Participation in the MBSR program and related group support allowed
participants to non-judgmentally observe and accept difficult thoughts, feelings,
and experiences associated with living with HIV and taking ART, which facilitated
greater reported adherence. Mindfulness training may stimulate new perspectives
and understanding, including greater self- and illness-acceptance among youth
living with HIV, leading to improved HIV outcomes.
PMID- 29961357
TI - An update on intracerebral stem cell grafts.
AB - INTRODUCTION: Primary neurological disorders are notoriously debilitating and
deadly, and over the past four decades stem cell therapy has emerged as a
promising treatment. Translation of stem cell therapies from the bench to the
clinic requires a better understanding of delivery protocols, safety profile, and
efficacy in each disease. Areas covered: In this review, benefits and risks of
intracerebral stem cell transplantation are presented for consideration.
Milestone discoveries in stem cell applications are reviewed to examine the
efficacy and safety of intracerebral stem cell transplant therapy for disorders
of the central nervous system and inform design of translatable protocols for
clinically feasible stem cell-based treatments. Expert commentary: Intracerebral
administration, compared to peripheral delivery, is more invasive and carries the
risk of open brain surgery. However, direct cell implantation bypasses the blood
brain barrier and reduces the first-pass effect, effectively increasing the
therapeutic cell deposition at its intended site of action. These benefits must
be weighed with the risk of graft-versus-host immune response. Rigorous clinical
trials are underway to assess the safety and efficacy of intracerebral
transplants, and if successful will lead to widely available stem cell therapies
for neurologic diseases in the coming years.
PMID- 29961359
TI - Allan McLane Hamilton.
PMID- 29961358
TI - Medication-Assisted Treatment for Alcohol-Dependent Adults With Serious Mental
Illness and Criminal Justice Involvement: Effects on Treatment Utilization and
Outcomes.
AB - OBJECTIVE: Adults with serious mental illness and comorbid alcohol dependence are
at high risk for both high utilization of crisis-driven health care services and
criminal justice involvement. Evidence-based medication-assisted treatment (MAT)
for alcohol dependence may reduce both crisis service utilization and criminal
recidivism. The authors estimated the effect of MAT on behavioral health
treatment utilization and criminal justice outcomes for this population. METHOD:
Relevant administrative data were merged from several public agencies in
Connecticut for 5,743 adults >=18 years old who had schizophrenia spectrum
disorder, bipolar disorder, or major depressive disorder comorbid with moderate
to severe alcohol dependence and who were incarcerated for at least one night
during the study window (2002-2009). Longitudinal multivariable regression models
were used to estimate the effect of MAT compared with other outpatient substance
abuse treatments on inpatient mental health and substance abuse hospitalizations,
emergency department visits, criminal convictions, and incarcerations. RESULTS:
MAT was associated with significant improvements in clinical outcomes in the 12
months following initiation compared with non-MAT comparison treatment, including
greater reductions in mental health hospitalization and emergency department
visits and greater improvements in psychotropic medication adherence. No benefits
of MAT were found for most criminal justice outcomes, except for significant
reductions in felony convictions among adults with bipolar disorder. CONCLUSIONS:
MAT is underused for treating alcohol dependence, especially among adults with
serious mental illness. These results suggest that MAT can have important
benefits for clinical outcomes in this population. More research is needed to
improve its use in this patient population as well as to address barriers to its
availability.
PMID- 29961360
TI - Comment on the Association of Hormonal Contraception With Suicide Attempts and
Suicides.
PMID- 29961361
TI - Reports to the Membership.
AB - The following are edited/abbreviated versions of the annual reports of the APA
Secretary, Treasurer, CEO and Medical Director, Speaker, and Speaker-Elect and
the chairpersons of the APA Committee on Bylaws, Membership Committee, Committee
of Tellers, and Elections Committee. The full reports were presented at the APA
Annual Business Meeting in New York, May 6, 2018.
PMID- 29961362
TI - Clarifying Methods and Results in Studies of the Association Between Hormonal
Contraception and Mental Health Issues: Response to Berlin et al.
PMID- 29961364
TI - Would Addressing Alcohol Consumption Further Account for Variance in Methylation?
PMID- 29961365
TI - Medication-Assisted Treatment for Alcohol Use Disorder: Hope for Incarcerated
Patients and for Our Communities.
PMID- 29961363
TI - Sensitization of the Neural Salience Network to Repeated Emotional Stimuli
Following Initial Habituation in Patients With Borderline Personality Disorder.
AB - OBJECTIVE: Borderline personality disorder is the prototypical disorder of
emotion reactivity and dysregulation, yet there remains limited understanding of
its neurocognitive correlates. Two mechanisms that may underlie anomalous
reactivity in response to negative stimuli among patients with borderline
personality disorder are impairment in habituation and exaggerated sensitization
of activity in the neural salience network, including the amygdala, anterior
insula, and dorsal anterior cingulate cortex. The authors aimed to reveal the
most plausible mechanism by examining the effect of repeated exposure to
emotional images both within and across study sessions. METHOD: A total of 75
participants (patients with borderline personality disorder, N=26; patients with
avoidant personality disorder included as a psychopathological control group,
N=25; and healthy control subjects, N=24) were included in the study analyses.
All participants viewed five presentations of the same set of negative and
neutral images at each of two sessions, separated by approximately 3 days, while
functional MRI data were acquired. Salience network activity, as measured by
blood-oxygen-level-dependent signal in anatomically defined regions of interest
across the salience network, was compared across the three groups for each
presentation at each of the two study sessions. Self-reported negative affect was
measured for each trial. RESULTS: Salience network activity showed a main effect
of within-session habituation across all groups and sessions. However, a group-by
session interaction was present, such that only patients with borderline
personality disorder showed increased salience network activity in response to
the images reencountered at the second session, and this increased salience
network sensitization predicted greater sensitization in self-reported negative
affect. CONCLUSIONS: These results elucidate the neural mechanisms by which
patients with borderline personality disorder appraise negative social situations
as exaggeratedly salient and suggest potential neurocognitive intervention
targets.
PMID- 29961366
TI - Abnormal Sensitization of Neural and Behavioral Responses to Socially Relevant
Images in Individuals With Borderline Personality Disorder: Implications for
Guiding More Effective Targeting of Treatments.
PMID- 29961367
TI - Antidepressant-Resistant Depression in Patients With Comorbid Subclinical
Hypothyroidism or High-Normal TSH Levels.
PMID- 29961368
TI - Can Personality Disorders Be Redefined in Personality Trait Terms?
PMID- 29961369
TI - Turning problems and freezing of gait in Parkinson's disease: a systematic review
and meta-analysis.
AB - OBJECTIVE: To understand the differences of step and turn parameters between
freezers and non-freezers during turning and determine the influence of turn
angle and turn characteristics on freezing of gait. DATA SOURCES: PubMed and Web
of Science were searched from the earliest data available to August 2017. STUDY
SELECTION: Case-control studies that examined the differences in turning while
walking between freezers and non-freezers were included. Two reviewers selected
studies independently. DATA EXTRACTION: Methodological quality was evaluated by
two independent reviewers using the STROBE checklist for case-control studies.
Mean differences and 95% confidence intervals were calculated from pooled data
for turn duration, peak turn velocity, number of steps and cadence. Center of
mass deviation, segmental rotation, phase coordination and freezing of gait
frequency were also extracted. When possible, different turning angles or spatial
confounds were compared. DATA SYNTHESIS: Sixteen studies met the inclusion
criteria. Freezing of gait occurred in 38.2% of the freezers. Freezing appeared
most frequently at the end of a turn and at the inner leg of the turn cycle. The
meta-analysis revealed that turning in freezers was characterized by an increased
turn duration, cadence and number of steps and a decreased peak turn velocity.
Qualitative analysis showed that results concerning step width, step length and
step time variability were inconsistent. Turning was characterized by an
increased head-pelvis coupling and worse coordination in freezers compared to non
freezers. A decreased medial deviation of the center of mass was present prior to
a freezing episode. CONCLUSIONS: Both step and rotational parameters differed in
freezers compared to non-freezers while turning. These differences increased with
increasing task complexity (i.e., larger turning angle or spatial confounds
during turning). The results suggest that improving axial rotation could be a
valuable rehabilitation target to ameliorate freezing. Implications for
rehabilitation Patients with freezing of gait turn with a larger arc and a
smaller angle compared to non-freezing patients Freezing-related turning deficits
have both spatiotemporal and rotational motor control components Improving axial
rotation could be a novel rehabilitation target to ameliorate freezing.
PMID- 29961370
TI - [Examination of sex chromosome abnormalities in childhood].
AB - INTRODUCTION: Early diagnosis of sex chromosome abnormalities is important
because of prevention, family planning and optimal therapy. AIM: Investigation of
the relationship between phenotype, age at time of diagnosis and therapeutic
options in sex chromosome aberrations. METHOD: Processing data of 51 children
with sex chromosome abnormalities who were diagnosed between 2009 and 2014 and
examined at the 2nd. Department of Pediatrics, Semmelweis University, by the
methods of anamnesis, family tree analysis, physical examination, karyotype
analysis and fluorescent in situ hybridisation. RESULTS: 41% of the patients were
diagnosed with Turner-, 18% with Klinefelter-, 10% with double-Y-, 6% with triple
and poly-X-syndrome, 19% with other gonadal dysgenesis and 6% with other
abnormality. The average age at diagnosis: Turner- and Klinefelter-syndrome 10
years, other gonadal dysgenesis 9 years, 46,XX,t(X;10) 17 years, other
abnormalities 1-2 years. CONCLUSIONS: Numerical aberrations of the sex
chromosomes are more common than structural aberrations. Klinefelter-, triple-
and poly-X-syndromes are underdiagnosed in childhood. Early diagnosis of Turner
syndrome and other gonadal dysgenesis is necessary to optimise therapy and
prevent associated diseases. This can be achieved by modern prenatal diagnostic
methods and targeted activity of family pediatricians. Orv Hetil. 2018; 159(27):
1121-1128.
PMID- 29961371
TI - [Prognostic significance of the total ischemic time in patients with ST-elevation
myocardial infarction].
AB - INTRODUCTION: The significance of the total ischemic time (from the beginning of
the complaint to the opening of the vessel) is an important factor for myocardial
salvage. AIM: The aim of the study was to determine the prognostic significance
of the TIT in patients with ST elevation myocardial infarction in Hungary.
METHOD: From 1 January 2014 all patients with myocardial infarction were recorded
by law in an on-line database of the Hungarian Myocardial Infarction Registry.
Between 1 January 2014 and 31 March 2016, 27 157 patients with 28 408 myocardial
infarction events were recorded. To investigate TIT, 7146 STEMI patients were
selected who were treated with percutaneous coronary intervention (PCI) within 24
hours of the beginning of the complaint and all of its components were known.
RESULTS: Average follow-up was 740 +/- 346 days. The median time of the TIT is
260 minutes, within which the earliest prehospital time was found (median 205
minutes). The TIT influenced survival: if this time was less than 400 minutes,
the 30-day and the 1-year deaths were 7.5% and 12.2%, respectively. In longer
TIT, higher mortality rate was found (9.2% versus 19.7%, respectively).
Multivariate analysis was performed for short (<30 days), medium (30-364 days)
and long-term (>=365 days) survival. Diabetes mellitus is a short-term prognostic
factor, abnormal creatinine, and severe coronary status have affected short and
medium survival. PCI was significant in terms of medium and long-term survival.
Previous myocardial infarction and TIT influenced the long-term survival
significantly. CONCLUSIONS: In Hungary, TIT is too long, and its dominant part
falls within the prehospital period. The TIT is an independent prognostic factor,
so reducing this time can improve the long-term prognosis of patients with ST
elevation myocardial infarction. Orv Hetil. 2018; 159(27): 1113-1120.
PMID- 29961372
TI - [The addictive model of obesity: psychoneurobiological relationships].
AB - Among the various etiological theories (e.g., psychosomatic stress) the addictive
model of obesity has also been described. Those suffering from eating disorders
triggered by emotional causes (in consequence of the reward system) tend to grab
a snack mostly out of happiness. The aim of the present study was to examine the
addictive model of obesity so that the relationships identified here could help
provide more accurate treatments to those suffering from being overweight. This
study identifies the anatomical, neurobiological and psychic relationships
between the etiological factors from the aspect of the addictive model of obesity
so that further logical relationships could be confirmed based on the conclusions
drawn here. Another system participating in energy homeostasis besides the
rewarding or dopamine controlling circles is the hypothalamic pro
opiomelanocortin (POMC) system. The effects and efficiency of these systems can
be modified by different biological factors and molecules. By exploring these
neurobiochemical processes it may become understandable why someone who is not
hungry will eat and have a tendency to overeat while others will not and why
someone is unable to lose weight permanently without relapse. Therefore in the
light of the findings further opportunities for intervention and treatment could
be identified (with drugs or by psychotherapy) which would allow us to develop
more sophisticated and tailor-made therapeutic solutions for the clinical picture
of obesity as well. Orv Hetil. 2018; 159(27): 1095-1102.
PMID- 29961374
TI - [Quality of life of asthmatic patients after complex rehabilitation treatment].
AB - Asthma is a serious public health challenge for all age groups around the world.
Heightened attention surrounds the use of the natural therapeutic factors that
potentially make medication more cost-efficient in the treatment of diseases. Our
research has tried to reveal how the medical conditions, quality of life of
asthmatic patients change after medical treatments that are accompanied by
climate therapy. Asthma patients (514 patients) participated in a 3-week complex
therapy at Matra Health Resort. Beyond medical examinations and treatments,
patients were involved in breathing exercises on the curing terraces or outdoors
twice a day, they were to attend the rehabilitative physical exercises led by a
physiotherapist once a day, were given dietetic and lifestyle advice and provided
with diets that were fitted to their individual medical conditions. Their
respiratory function was examined before the commencement of the cure as well as
after the therapy just before departing from the institution. The patients'
exercise capacities were assessed with the 6-minute walk test before the
treatment and then 3 weeks later. For the patients, a questionnaire was compiled
to reveal information in relation to their conditions in the first 6 months after
leaving the institution. Our results show that values of respiratory function in
the sample and 6-minute walk test significantly improved with the treatment.
After leaving the institute, the results of the Asthma Control Test in the 1st
month after treatment revealed a significantly better quality of life and better
control-level of patients than after the 3rd month. Orv Hetil. 2018; 159(27):
1103-1112.
PMID- 29961375
TI - Cerebral venous sinus thrombosis after vestibular schwannoma surgery: a call for
evidence-based management guidelines.
AB - OBJECTIVE Postoperative cerebral venous sinus thrombosis (CVST) is an uncommon
complication of posterior fossa surgery. The true incidence of and optimal
management strategy for this entity are largely unknown. Herein, the authors
report their institutional incidence and management experience of postoperative
CVST after vestibular schwannoma surgery. METHODS The authors undertook a
retrospective review of all vestibular schwannoma cases that had been treated
with microsurgical resection at a single institution from December 2011 to
September 2017. Patient and tumor characteristics, risk factors, length of stay,
surgical approaches, sinus characteristics, CVST management, complications, and
follow-up were analyzed. RESULTS A total of 116 patients underwent resection of
vestibular schwannoma. The incidence of postoperative CVST was 6.0% (7 patients).
All 7 patients developed lateral CVST ipsilateral to the lesion. Four cases
occurred after translabyrinthine approaches, 3 occurred after retrosigmoid
approaches, and none occurred following middle cranial fossa approaches. Patients
were managed with anticoagulation or antiplatelet therapy. Although patients were
generally asymptomatic, one patient experienced intraparenchymal hemorrhage,
epidural hemorrhage, and obstructive hydrocephalus, likely as a result of the
anticoagulation therapy. However, all 7 patients had a modified Rankin scale
score of 1 at the last follow-up. CONCLUSIONS Postoperative CVST is an infrequent
complication, with an incidence of 6.0% among 116 patients who had undergone
vestibular schwannoma surgery at one institution. Moreover, the management of
postoperative CVST with anticoagulation therapy poses a serious dilemma to
neurosurgeons. Given the paucity of reports in the literature and the low
incidence of CVST, additional studies are needed to better understand the cause
of thrombus formation and help to establish evidence-based guidelines for CVST
management and prevention.
PMID- 29961376
TI - Dynamic assessment of venous anatomy and function in neurosurgery with real-time
intraoperative multimodal ultrasound: technical note.
AB - The relevance of the cerebral venous system is often underestimated during
neurosurgical procedures. Damage to this draining system can have catastrophic
implications for the patient. Surgical decision-making and planning must consider
each component of the venous compartment, from the medullary draining vein to the
dural sinuses and extracranial veins. Intraoperative ultrasound (ioUS) permits
the real-time study of venous compartments using different modalities, thus
allowing complete characterization of their anatomical and functional features.
The B-mode (brightness mode) offers a high-resolution anatomical representation
of veins and their relationships with lesions. Doppler modalities (color, power,
spectral) allow the study of blood flow and identification of vessels to
distinguish their functional characteristics. Contrast-enhanced US allows one to
perform real-time angiosonography showing both the functional and the anatomical
aspects of vessels. In this technical report, the authors demonstrate the
different applications of multimodal ioUS in neurosurgery for identifying the
anatomical and functional characteristics of the venous compartment. They discuss
the general principles and technical nuances of ioUS and analyze their potential
implications for the study of various venous districts during neurosurgical
procedures.
PMID- 29961377
TI - Safety profile of superior petrosal vein (the vein of Dandy) sacrifice in
neurosurgical procedures: a systematic review.
AB - OBJECTIVE Walter E. Dandy described for the first time the anatomical course of
the superior petrosal vein (SPV) and its significance during surgery for
trigeminal neuralgia. The patient's safety after sacrifice of this vein is a
challenging question, with conflicting views in current literature. The aim of
this systematic review was to analyze the current surgical considerations
regarding Dandy's vein, as well as provide a concise review of the complications
after its obliteration. METHODS A systematic review was performed according to
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines. A thorough literature search was conducted on PubMed, Web of Science,
and the Cochrane database; articles were selected systematically based on the
PRISMA protocol and reviewed completely, and then relevant data were summarized
and discussed. RESULTS A total of 35 publications pertaining to the SPV were
included and reviewed. Although certain studies report almost negligible
complications of SPV sectioning, there are reports demonstrating the deleterious
effects of SPV obliteration when achieving adequate exposure in surgical
pathologies like trigeminal neuralgia, vestibular schwannoma, and petroclival
meningioma. The incidence of complications after SPV sacrifice (32/50 cases in
the authors' series) is 2/32 (6.2%), and that reported in various case series
varies from 0.01% to 31%. It includes hemorrhagic and nonhemorrhagic venous
infarction of the cerebellum, sigmoid thrombosis, cerebellar hemorrhage, midbrain
and pontine infarct, intracerebral hematoma, cerebellar and brainstem edema,
acute hydrocephalus, peduncular hallucinosis, hearing loss, facial nerve palsy,
coma, and even death. In many studies, the difference in incidence of
complications between the SPV-sacrificed group and the SPV-preserved group was
significant. CONCLUSIONS The preservation of Dandy's vein is a neurosurgical
dilemma. Literature review and experiences from large series suggest that
obliterating the vein of Dandy while approaching the superior cerebellopontine
angle corridor may be associated with negligible complications. However, the
counterview cannot be neglected in light of some series showing an up to 30%
complication rate from SPV sacrifice. This review provides the insight that
although the incidence of complications due to SPV obliteration is low, they can
happen, and the sequelae might be worse than the natural history of the existing
pathology. Therefore, SPV preservation should be attempted to optimize patient
outcome.
PMID- 29961378
TI - Bridging veins and veins of the brainstem in microvascular decompression surgery
for trigeminal neuralgia and hemifacial spasm.
AB - OBJECTIVE In microvascular decompression surgery for trigeminal neuralgia and
hemifacial spasm, the bridging veins are dissected to provide the surgical
corridors, and the veins of the brainstem may be mobilized in cases of venous
compression. Strategy and technique in dissecting these veins may affect the
surgical outcome. The authors investigated solutions for minimizing venous
complications and reviewed the outcome for venous decompression. METHODS The
authors retrospectively reviewed their surgical series of microvascular
decompression for trigeminal neuralgia and hemifacial spasm in patients treated
between 2005 and 2017. Surgical strategies included preservation of the superior
petrosal vein and its tributaries, thorough dissection of the arachnoid sleeve
that enveloped these veins, cutting of the inferior petrosal vein over the lower
cranial nerves, and mobilization or cutting of the veins of the brainstem that
compressed the nerve roots. The authors summarized the patient characteristics,
operative findings, and postoperative outcomes according to the vascular
compression types as follows: artery alone, artery and vein, and vein alone. They
analyzed the data using chi-square and 1-way ANOVA tests. RESULTS The cohort was
composed of 121 patients with trigeminal neuralgia and 205 patients with
hemifacial spasm. The superior petrosal vein and its tributaries were preserved
with no serious complications in all patients with trigeminal neuralgia. Venous
compression alone and arterial and venous compressions were observed in 4% and
22%, respectively, of the patients with trigeminal neuralgia, and in 1% and 2%,
respectively, of those with hemifacial spasm (p < 0.0001). In patients with
trigeminal neuralgia, 35% of those with artery and venous compressions and 80% of
those with venous compression alone had atypical neuralgia (p = 0.015). The
surgical cure and recurrence rates of trigeminal neuralgias with venous
compression were 60% and 20%, respectively, and with arterial and venous
compressions the rates were 92% and 12%, respectively (p < 0.0001, p = 0.04). In
patients with hemifacial spasm who had arterial and venous compressions, their
recurrence rate was 60%, and that was significantly higher compared to other
compression types (p = 0.0008). CONCLUSIONS Dissection of the arachnoid sleeve
that envelops the superior petrosal vein may help to reduce venous complications
in surgery for trigeminal neuralgia. Venous compression may correlate with worse
prognosis even with thorough decompression, in both trigeminal neuralgia and
hemifacial spasm.
PMID- 29961379
TI - Understanding the complex pathophysiology of idiopathic intracranial hypertension
and the evolving role of venous sinus stenting: a comprehensive review of the
literature.
AB - Idiopathic intracranial hypertension (IIH) is a disease defined by elevated
intracranial pressure without established etiology. Although there is now
consensus on the definition of the disorder, its complex pathophysiology remains
elusive. The most common clinical symptoms of IIH include headache and visual
complaints. Many current theories regarding the etiology of IIH focus on
increased secretion or decreased absorption of cerebrospinal fluid (CSF) and on
cerebral venous outflow obstruction due to venous sinus stenosis. In addition, it
has been postulated that obesity plays a role, given its prevalence in this
population of patients. Several treatments, including optic nerve sheath
fenestration, CSF diversion with ventriculoperitoneal or lumboperitoneal shunts,
and more recently venous sinus stenting, have been described for medically
refractory IIH. Despite the availability of these treatments, no guidelines or
standard management algorithms exist for the treatment of this disorder. In this
paper, the authors provide a review of the literature on IIH, its clinical
presentation, pathophysiology, and evidence supporting treatment strategies, with
a specific focus on the role of venous sinus stenting.
PMID- 29961380
TI - Use of ICG videoangiography and FLOW 800 analysis to identify the patient
specific venous circulation and predict the effect of venous sacrifice: a
retrospective study of 172 patients.
AB - OBJECTIVE The best management of veins encountered during the neurosurgical
approach is still a matter of debate. Even if venous sacrifice were to lead to
devastating consequences, under certain circumstances, it might prove to be
desirable, enlarging the surgical field or increasing the extent of resection in
tumor surgery. In this study, the authors present a large series of patients with
vascular or oncological entities, in which they used indocyanine green
videoangiography (ICG-VA) with FLOW 800 analysis to study the patient-specific
venous flow characteristics and the management workflow in cases in which a
venous sacrifice was necessary. METHODS Between May 2011 and December 2017, 1972
patients were admitted to the authors' division for tumor and/or neurovascular
surgery. They retrospectively reviewed all cases in which ICG-VA and FLOW 800
were used intraoperatively with a specific target in the venous angiographic
phase or for the management of venous sacrifice, and whose surgical videos and
FLOW 800 analysis were available. RESULTS A total of 296 ICG-VA and FLOW 800
studies were performed intraoperatively. In all cases, the venous structures were
clearly identifiable and were described according to the flow direction and
speed. The authors therefore defined different patterns of presentation:
arterialized veins, thrombosed veins, fast-draining veins with anterograde flow,
slow-draining veins with anterograde flow, and slow-draining veins with
retrograde flow. In 16 cases we also performed a temporary clipping test to
predict the effect of the venous sacrifice by the identification of potential
collateral circulation. CONCLUSIONS ICG-VA and FLOW 800 analysis can provide
complete and real-time intraoperative information regarding patient-specific
venous drainage pattern and can guide the decision-making process regarding
venous sacrifice, with a possible impact on reduction of surgical complications.
PMID- 29961381
TI - Retraction. Knowledge of skull base anatomy and surgical implications of human
sacrifice among pre-Columbian Mesoamerican cultures.
PMID- 29961382
TI - Introduction. Surgery involving the venous system and complication avoidance.
PMID- 29961383
TI - Transvenous embolization of brain arteriovenous malformations: a review of
techniques, indications, and outcomes.
AB - Endovascular embolization of brain arteriovenous malformations (AVMs) is
conventionally performed from a transarterial approach. Transarterial AVM
embolization can be a standalone treatment or, more commonly, used as a
neoadjuvant therapy prior to microsurgery or stereotactic radiosurgery. In
contrast to the transarterial approach, curative embolization of AVMs may be more
readily achieved from a transvenous approach. Transvenous embolization is
considered a salvage therapy in contemporary AVM management. Proposed indications
for this approach include a small (diameter < 3 cm) and compact AVM nidus, deep
AVM location, hemorrhagic presentation, single draining vein, lack of an
accessible arterial pedicle, exclusive arterial supply by perforators, and en
passage feeding arteries. Available studies of transvenous AVM embolization in
the literature have reported high complete obliteration rates, with reasonably
low complication rates. However, evaluating the efficacy and safety of this
approach is challenging due to the limited number of published cases. In this
review the authors describe the technical considerations, indications, and
outcomes of transvenous AVM embolization.
PMID- 29961384
TI - A review of extraaxial developmental venous anomalies of the brain involving
dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii,
venous varices or aneurysmal malformations, and enlarged emissary veins.
AB - This paper is a narrative review of extraaxial developmental venous anomalies
(eDVAs) of the brain involving dural venous flow or sinuses: persistent embryonic
sinuses, sinus pericranii, enlarged emissary veins, and venous varices or
aneurysmal malformations. The article highlights the natural history, anatomy,
embryology, imaging, clinical implications, and neurosurgical significance of
these lesions, which the authors believe represent a continuum, with different
entities characterized by distinct embryopathologic features. The indications and
surgical management options are discussed for these individual intracranial
pathologies with relevant illustrations, and a novel classification is proposed
for persistent falcine sinus (PFS). The role of neurointervention and/or
microsurgery in specific cases such as sinus pericranii and enlarged emissary
veins of the skull is highlighted. A better understanding of the pathophysiology
and developmental anatomy of these lesions can reduce treatment morbidity and
mortality. Some patients, including those with vein of Galen malformations
(VOGMs), can present with the added systemic morbidity of a high-output cardiac
failure. Although VOGM is the most studied and classified of the above-mentioned
eDVAs, the authors believe that grouping the former with the other venous
anomalies/abnormalities listed above would enable the clinician to convey the
exact morphophysiological configuration of these lesions, predict their natural
history with respect to evolving venous hypertension or stroke, and extrapolate
invaluable insights from VOGM treatment to the treatment of other eDVAs. In
recent years, many of these symptomatic venous malformations have been treated
with endovascular interventions, although these techniques are still being
refined. The authors highlight the broad concept of eDVAs and hope that this work
will serve as a basis for future studies investigating the role of evolving focal
venous hypertension/global intracranial hypertension and possibilities of fetal
surgical intervention in these cases.
PMID- 29961385
TI - Jugular bulb and skull base pathologies: proposal for a novel classification
system for jugular bulb positions and microsurgical implications.
AB - OBJECTIVE There is no definitive or consensus classification system for the
jugular bulb position that can be uniformly communicated between a radiologist,
neurootologist, and neurosurgeon. A high-riding jugular bulb (HRJB) has been
variably defined as a jugular bulb that rises to or above the level of the basal
turn of the cochlea, within 2 mm of the internal auditory canal (IAC), or to the
level of the superior tympanic annulus. Overall, there is a seeming lack of
consensus, especially when MRI and/or CT are used for jugular bulb evaluation
without a dedicated imaging study of the venous anatomy such as digital
subtraction angiography or CT or MR venography. METHODS A PubMed analysis of
"jugular bulb" comprised of 1264 relevant articles were selected and analyzed
specifically for an HRJB. A novel classification system based on preliminary
skull base imaging using CT is proposed by the authors for conveying the
anatomical location of the jugular bulb. This new classification includes the
following types: type 1, no bulb; type 2, below the inferior margin of the
posterior semicircular canal (SCC), subclassified as type 2a (without dehiscence
into the middle ear) or type 2b (with dehiscence into the middle ear); type 3,
between the inferior margin of the posterior SCC and the inferior margin of the
IAC, subclassified as type 3a (without dehiscence into the middle ear) and type
3b (with dehiscence into the middle ear); type 4, above the inferior margin of
the IAC, subclassified as type 4a (without dehiscence into the IAC) and type 4b
(with dehiscence into the IAC); and type 5, combination of dehiscences.
Appropriate CT and MR images of the skull base were selected to validate the
criteria and further demonstrated using 3D reconstruction of DICOM files. The
microsurgical significance of the proposed classification is evaluated with
reference to specific skull base/posterior fossa pathologies. RESULTS The authors
validated the role of a novel classification of jugular bulb location that can
help effective communication between providers treating skull base lesions.
Effective utilization of the above grading system can help plan surgical
procedures and anticipate complications. CONCLUSIONS The authors have proposed a
novel anatomical/radiological classification system for jugular bulb location
with respect to surgical implications. This classification can help surgeons in
complication avoidance and management when addressing HRJBs.
PMID- 29961387
TI - Retraction. A look at Mayan artificial cranial deformation practices:
morphological and cultural aspects.
PMID- 29961386
TI - Transverse venous stenting for the treatment of idiopathic intracranial
hypertension, or pseudotumor cerebri.
AB - OBJECTIVE Idiopathic intracranial hypertension (IIH) is a commonly occurring
disease, particularly among young women of child-bearing age. The underlying
pathophysiology for this disease has remained largely unclear; however, the
recent literature suggests that focal outflow obstruction of the transverse sinus
may be the cause. The purpose of this study was to report one group's early
experience with transverse venous sinus stenting in the treatment of IIH and
assess its effectiveness. METHODS The authors performed a retrospective chart
review to identify patients who had undergone stenting of an outflow-obstructed
transverse venous sinus for the treatment of IIH at Gates Vascular Institute
between January 2015 and November 2017. Patient demographic data of interest
included age, sex, BMI, and history of smoking, hypertension, obstructive sleep
apnea, hormonal contraceptive use, and acetazolamide therapy. Each patient's
presenting signs and symptoms and whether those symptoms improved with treatment
were reviewed. The average opening lumbar puncture (LP) pressure preprocedure,
average pressure gradient across the obstructed segment prior to stenting,
treatment failure rate (need for shunt placement), and mean follow-up period were
calculated. RESULTS Of the 18 patients who had undergone transverse venous
stenting for IIH, 16 (88.9%) were women. The mean age of all the patients was
38.3 years (median 38 years). Mean BMI was 34.2 kg/m2 (median 33.9 kg/m2).
Presenting symptoms were headache (16 patients [88.9%]), visual disturbances (13
patients [72.2%]), papilledema (8 patients [44.4%]), tinnitus (3 patients
[16.7%]), and auditory bruit (3 patients [16.7%]). The mean opening LP pressure
pre-procedure was 35.6 cm H2O (median 32 cm H2O). The mean pressure gradient
measured proximally and distally to the area of focal obstruction within the
transverse sinus was 16.5 cm H2O (median 15 cm H2O). Postprocedurally, 14
patients (77.8%) continued to have headaches; 6 (33.3%) continued to have visual
disturbances. No patients continued to have auditory bruit (0%) or papilledema
(0%). One patient (5.6%) had new-onset tinnitus postprocedure. Overall
improvement of symptoms was noted in 16 patients (88.9%) postprocedure, with 1
patient (5.6%) requiring shunt placement and 2 other patients (11.1%) requiring
postprocedural LP to monitor intracranial pressure to determine candidacy for
further surgical interventions to treat residual symptoms. The mean duration of
follow-up was 194.2 days. CONCLUSIONS Transverse sinus stenting is a rapidly
developing technique that has shown good effectiveness and safety in the
literature. Authors of the present study found that stenting a flow-obstructed
transverse sinus in patients with IIH was a safe and effective way to treat the
condition.
PMID- 29961388
TI - Cerebral venous thrombosis requiring invasive treatment for elevated intracranial
pressure in women with combined hormonal contraceptive intake: risk factors,
anatomical distribution, and clinical presentation.
AB - OBJECTIVE Women taking combined hormonal contraceptives (CHCs) are generally
considered to be at low risk for cerebral venous thrombosis (CVT). When it does
occur, however, intensive care and neurosurgical management may, in rare cases,
be needed for the control of elevated intracranial pressure (ICP). The use of
nonsurgical strategies such as barbiturate coma and induced hypothermia has never
been reported in this context. The objective of this study is to determine
predictive factors for invasive or surgical ICP treatment and the potential
complications of nonsurgical strategies in this population. METHODS The authors
conducted a 2-center, retrospective chart review of 168 cases of CVT in women
between 2000 and 2012. Eligible patients were classified as having had a mild or
a severe clinical course, the latter category including all patients who
underwent invasive or surgical ICP treatment and all who had an unfavorable
outcome (modified Rankin Scale score >= 3 or Glasgow Outcome Scale score <= 3).
The Mann-Whitney U-test was used for continuous parameters and Fisher's exact
test for categorical parameters, and odds ratios were calculated with statistical
significance set at p <= 0.05. RESULTS Of the 168 patients, 57 (age range 16-49
years) were determined to be eligible for the study. Six patients (10.5%)
required invasive or surgical ICP treatment. Three patients (5.3%) developed
refractory ICP > 30 mm Hg despite early surgical decompression; 2 of them (3.5%)
were treated with barbiturate coma and induced hypothermia, with documented
infectious, thromboembolic, and hemorrhagic complications. Coma on admission,
thrombosis of the deep venous system with consecutive hydrocephalus,
intraventricular hemorrhage, and hemorrhagic venous infarction were associated
with a higher frequency of surgical intervention. Coma, quadriparesis on
admission, and hydrocephalus were more commonly seen among women with unfavorable
outcomes. Thrombosis of the transverse sinus was less common in patients with an
unfavorable outcome, with similar distribution in patients needing invasive or
surgical ICP treatment. CONCLUSIONS The need for invasive or surgical ICP
treatment in women taking CHCs who have CVT is partly predictable on the basis of
the clinical and radiological findings on admission. The use of nonsurgical
treatments for refractory ICP, such as barbiturate coma and induced hypothermia,
is associated with systemic infectious and hematological complications and may
worsen morbidity in this patient population. The significance of these factors
should be studied in larger multicenter cohorts.
PMID- 29961389
TI - Editorial. The use of ICG videoangiography and FLOW 800 analysis.
PMID- 29961390
TI - Letter to the Editor. Errors in the meta-analysis of outcomes and complications
of MRgFUS.
PMID- 29961391
TI - Letter to the Editor. Magnetic resonance-guided focused ultrasound and essential
tremor.
PMID- 29961392
TI - miR-135 promotes proliferation and stemness of oesophageal squamous cell
carcinoma by targeting RERG.
AB - MicroRNA (miRNA) plays an important role in tumourigenesis and cancer development
by regulating oncogenes or tumour suppressor that are implicated in cell cycle,
cell mobility and even cell senescence. Due to the resistance to enzymes that
could degrade nucleotides, miRNAs have been considered proper for diagnosis and
prognosis evaluation of cancer. The present study was designed to investigate
miRNA associated with ESCC and identified effective miRNAs, which could serve as
biomarker or targets. We first performed miRNA profiling to identify a subset of
dysregulated miRNAs in ESCC. miR-135, miR-451 and miR-186 were the most
differentially expressed miRNAs. Subsequent RT-PCR validated that miR-135 was
upregulated in ESCC cell lines TE2 and TE9, implying the promise as a prognostic
and diagnostic marker. The Cox regression analysis suggests the correlation of
miR-135 expression and tumour stages. Survival analysis demonstrated metastatic
samples largely have higher miR-135 expression. Downregulation of miR-135
suppressed proliferation and invasion of TE2 and TE9 cell lines. Subsequent
target prediction combined with functional enrichment analysis identified "Small
GTPase superfamily" that are possibly targeted by miR-135, which offers
candidates for further investigation. Finally, RERG was identified as a target of
miR-135. Downregulation of RERG could inhibit the cell proliferation and sphere
formation ability of TE2 and TE9. Taken together, miR-135 was proved to promote
tumour development of ESCC, which promises the prospect of using miR-135 as a
biomarker indicator in diagnosis and prognosis.
PMID- 29961393
TI - Polarity and morphogenesis of the eye epithelium requires the adhesion junction
associated adaptor protein Traf4.
AB - During development, neuroepithelial progenitors acquire apico-basal polarity and
adhere to one another via apically located tight and adherens junction complexes.
This polarized neuroepithelium must continue to integrate cells arising through
cell divisions and intercalation, and allow for cell movements, at the same time
as undergoing morphogenesis. Cell proliferation, migration and intercalation all
occur in the morphing embryonic eye. To understand how eye development might
depend on dynamic epithelial adhesion, we investigated the function of a known
regulator of junctional plasticity, Tumour necrosis factor receptor-associated
factor 4 (Traf4). traf4a mRNA is expressed in the developing eye vesicle over the
period of optic cup morphogenesis, and Traf4a loss leads to disrupted evagination
and elongation of the eye vesicles, and aberrant organization and apico-basal
polarity of the eye epithelium. We propose a model whereby Traf4a regulates
apical junction plasticity in nascent eye epithelium, allowing for its
polarization and morphogenesis. Symbols and Abbreviations: AB: apico-basal; aPKC:
atypical protein kinase-C; CRISPR: clustered regularly-interspaced short
palindromic repeats; GFP: green fluorescent protein; hpf: hours post
fertilization; MO: antisense morpholino oligonucleotide; pHH3: phospho histone
H3; ss: somite stage; Traf4: Tumour necrosis factor receptor-associated factor 4;
ZO-1: zona occludens-1.
PMID- 29961394
TI - Chondroid Differentiation in Thyroid Nodular Hyperplasia: An Innocent Bystander?
PMID- 29961395
TI - Ruptures in psychotherapy: Experiences of therapist trainees.
AB - METHOD: We used consensual qualitative research (CQR) to investigate the
experiences of therapist trainees who had a rupture with a client. RESULTS: Of 21
trainees who were tracked weekly, 14 experienced a rupture and were interviewed 1
week after the rupture and again 2 weeks later about antecedents, repair
attempts, and consequences. Trainees typically reported experiencing tension at
the beginning of the rupture session and difficult emotions during the rupture
(e.g., anger, depleted self-efficacy). CONCLUSION: Trainees typically tried to
repair the rupture by using immediacy or facilitating exploration about the
conflict. Trainees typically reported both negative (e.g., strained therapeutic
relationship) and positive consequences (e.g., therapeutic work became more
productive). Trainees seemed to be less aware of withdrawal than confrontational
ruptures. Implications are that trainees could benefit from learning more about
ruptures including how to regulate negative emotions toward clients and acquiring
more rupture-repair tools, as well as realizing that ruptures can have some
positive as well as negative aspects.
PMID- 29961396
TI - Maternal serum uric acid levels in pregnancy and fetal growth.
AB - OBJECTIVE: Studies of maternal serum uric acid (UA) in pregnancy focus primarily
on high levels of UA, however, both low and high UA levels can be markers of
oxidative stress, a biological state potentially linked to fetal growth. We
therefore aimed to test whether low and high maternal serum UA levels during
pregnancy are associated with atypical fetal growth (unusually small or large)
measured as birthweight (BW) for gestational age. METHODS: The Pregnancy Outcomes
and Community Health Study enrolled 3019 pregnant women between their 16th-27th
week of pregnancy from 52 clinics in five Michigan communities (1998-2004).
Maternal UA levels were measured in blood collected at enrollment among a
subcohort of 1291 participants. Infant BW and gestational age were used to
calculate gestational age-specific BW Z-score. Infants were grouped as small (SGA
= BW < 10th percentile), appropriate (AGA = BW 10th-90th percentile), or large
(LGA) = BW > 90th percentile) for their gestational age. Analyses considered
multiple potential confounders. Linear spline or multiple linear regression
models were applied to evaluate the relationship between maternal UA levels and
BW Z-score overall and within SGA, AGA, and LGA groups. Model robustness was
tested through bootstrap, sensitivity analysis, and cross-validation techniques.
RESULTS: The relation between maternal UA levels and BW Z-score varied by infant
group. Among SGA infants, the relation was nonlinear (J-shape): both extremes of
UA had lower BW Z-score with a breakpoint of 0.267 mmol/L UA (adjusted regression
coefficient beta = 2.32, p = .01 for lower UA; adjusted beta = -37.38, p < .01
for higher UA). Among AGA infants, there was no significant association, and
among LGA infants, the relation was linear (adjusted beta = 2.86, p = .03).
CONCLUSIONS: Future research on maternal UA levels in pregnancy may benefit from
considering both very low and high levels, and identifying in utero conditions
associated with the two extremes.
PMID- 29961397
TI - Oxidative insults disrupt OPA1-mediated mitochondrial dynamics in cultured
mammalian cells.
AB - OBJECTIVE: To explore the impact of oxidative insults on mitochondrial dynamics.
In mammalian cells, oxidative insults activate stress response pathways including
inflammation, cytokine secretion, and apoptosis. Intriguingly, mitochondria are
emerging as a sensitive network that may function as an early indicator of
subsequent cellular stress responses. Mitochondria form a dynamic network,
balancing fusion, mediated by optic atrophy-1 (OPA1), and fission events,
mediated by dynamin-related protein-1 (DRP1), to maintain homeostasis. METHODS:
Here, we examine the impact of oxidative insults on mitochondrial dynamics in
143B osteosarcoma and H9c2 cardiomyoblast cell lines via confocal microscopy,
flow cytometry, and protein-based analyses. RESULTS: When challenged with
hydrogen peroxide (H2O2), a ROS donor, both cell lines display fragmentation of
the mitochondrial network and loss of fusion-active OPA1 isoforms, indicating
that OPA1-mediated mitochondrial fusion is disrupted by oxidative damage in
mammalian cells. Consistent with this, cells lacking OMA1, a key protease
responsible for cleavage of OPA1, are protected against OPA1 cleavage and
mitochondrial fragmentation in response to H2O2 challenge. DISCUSSION: Taken
together, these findings indicate that oxidative insults damage OPA1-mediated
mitochondrial dynamics in mammalian cells via activation of OMA1, consistent with
an emerging role for mitochondrial dynamics as an early indicator of cellular
stress signaling.
PMID- 29961399
TI - Suiga/Change: An Ethnodrama Exploring Challenges in Intimate Relationships With
Young People in Samoa.
AB - Intimate partner violence (IPV) is a significant global issue and there is an
immediate need to strengthen knowledge and support innovative action,
particularly with young people and people in diverse cultural settings. This
ethnodrama provides insights into the way young people in Samoa, a Pacific Island
nation reporting high rates of IPV, experience and perceive IPV and challenges
within intimate relationships. Suiga/Change is an authentic, emotive, and
powerful story of four young people who represent the diversity and lived
experiences of the wider population of young people in Samoa. Implications for
future research and practice are discussed.
PMID- 29961398
TI - Protein-restricted maternal diet during lactation decreases type I and type III
tropocollagen synthesis in the skin of mice offspring.
AB - We investigated the effects of a low protein (LP) maternal diet during lactation
on type I and III tropocollagen synthesis in infant mouse skin. The LP diet
decreased the levels of type I and III tropocollagen proteins and COL1A1 and
COL3A1 mRNA. Thus, the protein composition of the maternal perinatal diet may
influence the skin health of offspring.
PMID- 29961400
TI - Expanding and Validating a Typology of Intimate Partner Violence: Intersections
of Violence and Control Within Relationships.
AB - This research explored an expanded typology of intimate partner violence (IPV),
intersecting violent and controlling behaviors of partners. Secondary data were
analyzed ( n = 714). Cluster analyses indicated that elements of IPV (control
perpetration, control victimization, violence victimization, and violence
perpetration) all clustered in high/low patterns, which intersected to form 10
unique categories of IPV. Support for all of Johnson's categories of IPV was
found, but there was also evidence for the three control-related categories:
Unidirectional Control, Bidirectional Control, and Control Resistance. This
expanded typology can move research, practice, and policies beyond the gender
symmetry debate.
PMID- 29961401
TI - Malignant Solitary Fibrous Tumor of the Humerus: A Case Report of an Extremely
Rare Primary Bone Tumor.
AB - Solitary fibrous tumor (SFT) is a spindle-shaped cell neoplasm originally
described in the pleura, but subsequently found in many anatomic sites. Only few
cases of primary SFTs in the bone have been previously described in the
literature. We present the case of an 86-year-old man with a 1-week history of
pain in his left arm. Imaging studies demonstrated a well-defined osteolytic
lesion in the proximal humerus measuring 6.1 cm in diameter. Sections showed a
round to spindle-shaped cell neoplasm with prominent mitotic activity (28 mitoses
per 10 high-power fields) and areas of necrosis, focally surrounding staghorn
shaped vessels. The tumor cells were positive for CD34, CD99, Bcl-2, and STAT6
and negative for smooth muscle actin, epithelial membrane antigen, and
cytokeratin AE1/AE3. These findings were consistent with a malignant SFT
involving the left humerus. Although extremely rare, SFT should be considered in
the differential diagnosis of primary bone tumors. This is the first case report
of a primary SFT in a long bone with malignant histological features.
PMID- 29961402
TI - Primary Hepatoid Carcinoma of the Pancreas: A Clinicopathological Study of 3
Cases With Review of Additional 31 Cases in the Literature.
AB - Primary pancreatic hepatoid carcinoma (PHC) is very rare. Here, we reported 3
such cases with review of additional 31 cases in the literature. Our 3 patients
were male (83, 72, and 54 years old, respectively). Serum alpha-fetoprotein (AFP)
was elevated in 1 patient (case 3, 8338 ng/mL) and not measured in the other two.
The PHC in patient 1 (pathological stage pT2N0M0) and patient 2 (pT3N0M0) showed
pure hepatocellular carcinoma (HCC)-like morphology, whereas in case 3 it was a
PHC with true glandular differentiation (pT4N0M0). The diagnosis of PHC was
confirmed with positive immunohistochemical staining in the tumor cells for AFP
(2/3), Hep Par 1 (3/3), glypican-3 (2/3), arginase-1 (2/3), and Sal-like protein
4 (1/3). CD10 and polyclonal carcinoembryonic antigen stains show focal
canalicular pattern in 2/3 tumors. Patient 1 did not receive further treatment
after resection and was alive with no evidence of disease at 107 months. Patient
2 died of postoperative complications, whereas patient 3 received postsurgical
chemoradiation and died of disease at 29 months. Our findings and literature
review indicate that PHCs can be divided into 4 histological subtypes: with pure
HCC-like morphology (n = 22), with neuroendocrine differentiation (n = 8), with
true glandular differentiation (n = 3), and with acinar cell differentiation (n =
1). On univariate analysis, pure HCC-like morphology was associated with better
disease-specific survival (DSS; P = .04), whereas lymph node and distant
metastases were associated with worse DSS ( P = .002 for both). Age, gender,
presenting symptoms, serum AFP level, and T stage were not associated with DSS.
On multivariate analysis, none of these parameters was significantly associated
with DSS.
PMID- 29961404
TI - Rheumatic manifestations of inflammatory bowel diseases: A study from the Middle
East.
AB - Objective To examine the prevalence of rheumatic manifestations among patients
with inflammatory bowel disease (IBD). Methods This prospective study enrolled
patients with IBD in whom the diagnosis and extent of IBD were confirmed by
colonoscopy and histopathology. Patients were interviewed and examined by a
rheumatologist. A complete rheumatological examination, X-rays of the lumbosacral
and sacroiliac joints and HLA-B27 blood tests were performed. Results A total of
127 adult patients were recruited: 46 (36.2%) with Crohn's disease (CD) and 81
(63.8%) with ulcerative colitis (UC). Rheumatic manifestations of any type were
present in 57.5% (73 of 127 patients) with no significant differences between CD
and UC. Peripheral manifestations were present in 43.3% (55 of 127 patients),
four patients (3.1%) had axial arthritis alone and 14 patients (11.0%) had both
types. Among those with peripheral manifestations, five patients (7.2%) had type
1 arthritis (pauciarticular) and one patient (1.4%) had type 2 arthritis
(polyarticular). A higher proportion of patients with CD had axial manifestations
with or without peripheral manifestations (eight of 46; 17.4%) compared with
patients with UC (10 of 81; 12.3%), but no difference was observed in patients
with peripheral manifestations alone. Conclusions Rheumatic manifestations in
patients with IBD in Qatar are more prevalent than in other regions of the world.
Peripheral manifestations were more prevalent than axial.
PMID- 29961405
TI - Contextual factors on physical demands in professional women's soccer: Female
Athletes in Motion study.
AB - The aim of this study was to examine the impact of contextual factors on relative
locomotor and metabolic power distances during professional female soccer
matches. Twenty-eight players (forwards, n = 4; midfielders, n = 12; defenders, n
= 12) that competed in a 90-min home and away match (regular season only). The
generalised estimating equations (GEE) was used to evaluate relative locomotor
and metabolic power distances for three contextual factors: location (home vs.
away), type of turf (natural vs. artificial), and match outcome (win, loss and
draw). No differences were observed for home vs. away matches. Moderate-intensity
running (20.0 +/- 1.0 m min-1 and 16.4 +/- 0.9 m min-1), high-intensity running
(8.6 +/- 0.4 m min-1 and 7.3 +/- 0.4 m min-1) and high-metabolic power (16.3 +/-
0.5 m min-1 and 14.4 +/- 0.5 m min-1) distances were elevated on artificial turf
compared to natural grass, respectively. Relative sprint distance was greater
during losses compared with draws (4.3 +/- 0.4 m min-1 and 3.4 +/- 0.3 m min-1).
Overall physical demands of professional women's soccer were not impacted by
match location. However, the elevation of moderate and high-intensity demands
while playing on artificial turf may have implications on match preparations as
well as recovery strategies.
PMID- 29961403
TI - Rosuvastatin alleviates high-salt and cholesterol diet-induced cognitive
impairment in rats via Nrf2-ARE pathway.
AB - OBJECTIVE: The objectives of our study were to investigate the possible effect of
rosuvastatin in ameliorating high salt and cholesterol diet (HSCD)-induced
cognitive impairment and to also investigate its possible action via the Nrf2-ARE
pathway. METHODS: In silico studies were performed to check the theoretical
binding of rosuvastatin to the Nrf2 target. HSCD was used to induce cognitive
impairment in rats and neurobehavioral studies were performed to evaluate the
efficacy of rosuvastatin in enhancing cognition. Biochemical analyses were used
to estimate changes in oxidative markers. Western blot and immunohistochemical
analyses were done to check Nrf2 translocation. TUNEL and caspase 3 tests were
performed to evaluate reversal of apoptosis by rosuvastatin. RESULTS:
Rosuvastatin showed good theoretical affinity to Nrf2, significantly reversed
changes in oxidative biomarkers which were induced by HSCD, and also improved the
performance of rats in the neurobehavioral test. A rise in nuclear translocation
of Nrf2 was revealed through immunohistochemical analysis and western blot. TUNEL
staining and caspase 3 activity showed attenuation of apoptosis. DISCUSSION: We
have investigated a novel mechanism of action for rosuvastatin (via the Nrf2-ARE
pathway) and demonstrated that it has the potential to be used in the treatment
of cognitive impairment.
PMID- 29961406
TI - Potential effect of maternal dietary sucrose or fructose syrup on CD36, leptin,
and ghrelin-mediated fetal programming of obesity.
AB - The influence of HFCS (high fructose corn syrup - free fructose) and sucrose
(bound fructose) on fetal appetite signals is unknown. This study aimed to
determine the effects of HFCS or sucrose on the peptide-mediated appetite
regulation in fetal programming of obesity. Sprague Dawley female rats were
administered feed and plain water (control) or water containing maltodextrin
(vehicle), sucrose, fructose, or HFCS (20%, w/v) for 12 weeks before mating and
throughout pregnancy and lactation (ndams = 31; npups = 207). Maternal chow-feed
consumption in the HFCS and sucrose groups and sugar-added drink consumption in
the HFCS group were higher compared to the vehicle and control groups (P < 0.05).
The total body fat accumulated in sucrose, fructose, and HFCS groups in dams and
pups was higher than those in the vehicle and control groups (P < 0.05). The HFCS
groups showed lower plasma leptin levels and higher ghrelin levels. Soluble CD36
levels in plasma and tongue samples were high in HFCS groups of dams and pups (P
< 0.05). Rather than bound fructose, the free fructose from the maternal diet
contributes to the programming of obesity through the disruption of leptin,
ghrelin, and CD36 expression involved in appetite regulation.
PMID- 29961407
TI - Maternal and neonatal outcomes following expectant management of preterm prelabor
rupture of membranes before viability.
AB - PURPOSE: To provide center-based outcome data on obstetric and neonatal
complications arising from expectantly managed pregnancies affected by preterm
prelabor rupture of membranes (PPROM) before viability. MATERIALS AND METHODS: We
collected data on 130 consecutive pregnancies complicated by spontaneous rupture
of membranes before 24 week's gestation, occurring over a 7-year period. These
were women who delivered >24 h after membrane rupture, and had no signs of
chorioamnionitis or advanced labor at admission. Women with amniocentesis-induced
PPROM (n = 7) were analyzed separately. The descriptive statistics of obstetrics
and neonatal outcomes were reported. RESULTS: The overall neonatal survival to
discharge rate was 33.8%. Stratification of patients into early (12 to 19+6
weeks' gestation) and late pre-viable PPROM (20 to 23+6 weeks' gestation)
revealed a 3.6-fold increase in survival rate in the latter group (12.2% versus
43.8%, p < .001). Pre-viable PPROM following amniocentesis predicted a 100%
survival outcome, however anhydramnios impacted negatively. The most common
neonatal morbidities of those admitted to intensive care unit were respiratory
distress syndrome (78.7%) and bronchopulmonary dysplasia (84.4%). The most common
maternal morbidities affecting pre-viable PPROM were clinical chorioamnionitis
(47.7%), histological chorioamnionitis (81.8%), retained products of conception
(39.3%) and preterm labor (45.4%). CONCLUSIONS: Later gestational ages at PPROM
were associated with better survival rates, however neonatal morbidity remained
high. Women experiencing pre-viable PPROM following amniocentesis can be
reassured, while those with anhydramnios at any time during the latency period
should be adequately counseled regarding poorer outcomes.
PMID- 29961409
TI - Perception Matters: The Pitfalls of Misperceiving Psychological Barriers to
Climate Policy.
PMID- 29961408
TI - Open Science Is Liberating and Can Foster Creativity.
AB - Some scholars think that Open Science practices constrain researchers in ways
that reduce their creativity, arguing, for instance, that preregistration
discourages data exploration and so stifles discovery. In this article, we argue
the opposite: Open Science practices are liberating and can foster creativity.
Open Science practices are liberating because they (a) enable us to explore data
transparently and comfortably; (b) reward quality, which is under our control,
rather than outcomes, which are not; and (c) reduce the choke hold of needing to
find "positive" results for career advancement. Open Science practices can foster
creativity because they cultivate an open and flexible mind-set, create a more
collaborative and constructive climate, and generate more accurate information
and make it more accessible. In sum, Open Science liberates researchers more than
it constrains them.
PMID- 29961410
TI - Implications of the Credibility Revolution for Productivity, Creativity, and
Progress.
AB - The credibility revolution (sometimes referred to as the "replicability crisis")
in psychology has brought about many changes in the standards by which
psychological science is evaluated. These changes include (a) greater emphasis on
transparency and openness, (b) a move toward preregistration of research, (c)
more direct-replication studies, and (d) higher standards for the quality and
quantity of evidence needed to make strong scientific claims. What are the
implications of these changes for productivity, creativity, and progress in
psychological science? These questions can and should be studied empirically, and
I present my predictions here. The productivity of individual researchers is
likely to decline, although some changes (e.g., greater collaboration, data
sharing) may mitigate this effect. The effects of these changes on creativity are
likely to be mixed: Researchers will be less likely to pursue risky questions;
more likely to use a broad range of methods, designs, and populations; and less
free to define their own best practices and standards of evidence. Finally, the
rate of scientific progress-the most important shared goal of scientists-is
likely to increase as a result of these changes, although one's subjective
experience of making progress will likely become rarer.
PMID- 29961411
TI - From Outcome to Process Focus: Fostering a More Robust Psychological Science
Through Registered Reports and Results-Blind Reviewing.
AB - A variety of alternative mechanisms, strategies, and "ways of doing" have been
proposed for improving the rigor and robustness of published research in the
psychological sciences in recent years. In this article, we describe two existing
but underused publication models-registered reporting (RR) and results-blind
reviewing (RBR)-that we believe would contribute in important ways to improving
both the conduct and evaluation of psychological research. We first outline the
procedures and distinguishing features of both publication pathways and note
their value for promoting positive changes to current scientific practices. We
posit that a significant value of RR and RBR is their potential to promote a
greater focus on the research process (i.e., how and why research is conducted)
relative to research outcomes (i.e., what was observed or concluded from
research). We conclude by discussing what we perceive to be five common beliefs
about RR and RBR practices and attempt to provide a balanced perspective of the
realities likely to be experienced with these systems.
PMID- 29961412
TI - Psychological Barriers to Bipartisan Public Support for Climate Policy.
AB - Psychological scientists have the expertise-and arguably an obligation-to help
understand the political polarization that impedes enactment of climate policy.
Many explanations emphasize Republican skepticism about climate change. Yet
results from national panel studies in 2014 and 2016 indicate that most
Republicans believe in climate change, if not as strongly as Democrats. Political
polarization over climate policy does not simply reflect that Democrats and
Republicans disagree about climate change but that Democrats and Republicans
disagree with each other. The results of a national panel experiment and of in
depth interviews with four former members of Congress suggest that Democrats and
Republicans-both ordinary citizens and policymakers-support policies from their
own party and reactively devalue policies from the opposing party. These partisan
evaluations occur both for policies historically associated with liberal
principles and politicians (cap-and-trade) and for policies associated with
conservative principles and politicians (revenue-neutral carbon tax). People also
exaggerate how much other Democrats and Republicans are swayed by partisanship.
This foments false norms of partisan opposition that, in turn, influence people's
personal policy support. Correcting misperceived norms of opposition and
decoupling policy evaluation from identity concerns would help overcome these
seemingly insurmountable barriers to bipartisan support for climate policy.
PMID- 29961413
TI - The Creativity-Verification Cycle in Psychological Science: New Methods to Combat
Old Idols.
AB - Over the years, researchers in psychological science have documented and
investigated a host of powerful cognitive fallacies, including hindsight bias and
confirmation bias. Researchers themselves may not be immune to these fallacies
and may unwittingly adjust their statistical analysis to produce an outcome that
is more pleasant or better in line with prior expectations. To shield researchers
from the impact of cognitive fallacies, several methodologists are now advocating
preregistration-that is, the creation of a detailed analysis plan before data
collection or data analysis. One may argue, however, that preregistration is out
of touch with academic reality, hampering creativity and impeding scientific
progress. We provide a historical overview to show that the interplay between
creativity and verification has shaped theories of scientific inquiry throughout
the centuries; in the currently dominant theory, creativity and verification
operate in succession and enhance one another's effectiveness. From this
perspective, the use of preregistration to safeguard the verification stage will
help rather than hinder the generation of fruitful new ideas.
PMID- 29961414
TI - The Impact of Changing Norms on Creativity in Psychological Science.
AB - The open science or credibility revolution has divided psychologists on whether
and how the "policy" change of preregistration and similar requirements will
affect the quality and creativity of future research. We provide a brief history
of how norms have rapidly changed and how news and social media are beginning to
"disrupt" academic science. We note a variety of benefits, including more
confidence in research findings, but there are possible costs as well, including
a reduction in the number of studies conducted because of an increased workload
required by new policies. We begin to craft a study to evaluate the short- and
long-term impacts of these changing norms on creativity in psychological science,
run into some possible roadblocks, and hope others will build on this idea. This
policy change can be evaluated in the short term but will ultimately need to be
evaluated decades from now. Long-term evaluations are rare, yet this is the
ultimate measure of creative scientific advance. Our conclusion supports the
goals and procedures for creating a more open science.
PMID- 29961415
TI - Toward Surmounting the Psychological Barriers to Climate Policy-Appreciating
Contexts and Acknowledging Challenges: A Reply to Weber (2018).
AB - The authors acknowledge and respond to three concerns raised by Weber (2018)
about oversimplifying psychological barriers to climate policy. First, skepticism
about climate change remains a major barrier to climate policy, along with
political partisanship. Second, recognizing multifaceted barriers to climate
policy calls for multiple targeted interventions to be implemented at critical
junctures. Finally, translating pro-environmental attitudes into action requires
an appreciation of proximate sociopolitical contexts and cultures. Rather than a
one-size-fits-all approach, psychological scientists are well equipped to
understand and address the complex barriers to climate policy within the natural
flow of everyday social life.
PMID- 29961416
TI - The Creative Cycle and the Growth of Psychological Science.
AB - Scientific progress relies on the dialectics of loosening and tightening
processes. Although most gripping accomplishments in psychological science
testify to the critical role of creative and innovative theorizing (loosening),
the ongoing debate on the quality of psychological science is focused almost
totally on a restrictive sense of tightening, revolving around statistical
hypothesis testing (tightening). A discussion of the imbalance between the
conspicuous neglect of theory and the overstated importance of the sacred cow of
significance testing raises a skeptical question: Do we seriously believe that
stricter compliance rules, exact p values, effect size calculations, new
statistics, and monitoring of research practices will foster the growth of
excellent science? A more effective strategy would be to start a positive debate
that focuses on the best exemplars of strong theorizing and fascinating findings,
replacing the focus on insufficient science and unwanted practices.
PMID- 29961417
TI - Replication, Registration, and Scientific Creativity.
AB - The bureaucratization of psychological science exacts intellectual costs that go
beyond the sheer amount of time that is drained away from creative scientific
activity. Additional administrative hurdles are now being generated in an attempt
to ensure the replicability of psychological effects. A cognitive analysis of
those hurdles shows that impairment of scientific creativity is a foreseeable
consequence, owing to their frequent verbatim-processing focus and the negative
emotional context in which they are embedded. We consider whether it is possible
to enhance replicability without increasing bureaucratic obstacles and to enhance
scientific creativity in the presence of such obstacles.
PMID- 29961418
TI - The Road to Uncreative Science Is Paved With Good Intentions: Ideas,
Implementations, and Uneasy Balances.
AB - How does the current replication crisis, along with other recent psychological
trends, affect scientific creativity? To answer this question, we consider
current debates regarding replication through the lenses of creativity research
and theory. Both scientific work and creativity require striking a balance
between ideation and implementation and between freedom and constraints. However,
current debates about replication and some of the emerging guidelines stemming
from them threaten this balance and run the risk of stifling innovation. Although
we recognize the importance of doing rigorous science, we argue that any "one
size fits all" research guidelines being proposed or enforced will do more harm
than good for scientific creativity.
PMID- 29961419
TI - Novel Xanthine Oxidase (XO) inhibitory phenylindanes produced by thermal reaction
of caffeic acid.
AB - The products from the thermal reaction of chlorogenic and caffeic acids, which is
a model process of roasting coffee beans, exhibited xanthine oxidase (XO)
inhibitory activity. From caffeic acid, six inhibitory phenylindanes were
identified, and a new phenylindane displayed the highest inhibitory activity
among them. The activity of these phenylindanes may contribute to XO inhibition
related functions of roasted coffee beverages.
PMID- 29961420
TI - A biophysically-defined hyaluronic acid-based compound accelerates migration and
stimulates the production of keratinocyte-derived neuromodulators.
AB - Hyaluronic acid (HA) preparations are widely used in clinical practice and recent
data suggest that commercially available HA-based compounds promote ulcer re
epithelialization and induce pain relief. However, the pathophysiological basis
of these effects remains poorly understood. In the present study, we investigated
the biophysical, biomolecular and functional properties of a HA preparation
combined with a pool of collagen precursor synthetic aminoacids, namely l
proline, l-leucine, l-lysine and glycine (Aminogam(r)). Hydrodynamic
characterization of Aminogam(r) by size exclusion chromatography-triple detector
array (SEC-TDA) revealed an average molecular weight in the range of 700-1700
kDa. Rheological measurements of the 1700kDa Mw lot showed a pseoudoplastic
behaviour with a zero-shear viscosity (eta0) equal to 90 +/- 9 Pa?s at 25 degrees
C and 55 +/- 6 Pa?s at 37 degrees C. Automated time-lapse videomicroscopy studies
in a fibroblast-free system demonstrated that 1% (v/v) Aminogam(r) significantly
reduced the healing time of wounded keratinocyte monolayers. In AKGOS assays,
Aminogam(r) stimulated cellular locomotion (chemokinesis) and directional
migration (chemotaxis) of keratinocytes. Analysis of microarray data suggested
that keratinocytes had a functional neuroendocrine machinery, and this was
confirmed by testing the secretion of six neuroactive molecules by ELISA, namely
alpha-MSH, beta-endorphins, melatonin, substance P, cortisol, and neurotensin.
Interestingly, Aminogam(r) regulated the production of several neuropeptides,
including beta-endorphins. In conclusion, our data shed light on the epithelial
dependent mechanisms that underlie the efficacy of Aminogam(r), particularly in
reference to wound healing and nociception.
PMID- 29961421
TI - Monitoring anoxic depolarization at the bedside: A step closer to the 24th
century.
AB - Anoxic depolarization starts the clock for irreversible brain injury. Yet, this
critical indicator has been highly elusive and notoriously difficult to capture
using currently available clinical monitoring tools. Recent data suggest that it
may be possible to detect anoxic depolarization at the bedside. Detection of such
terminal events has far-reaching implications for diagnosis, prognostication, and
neuroprotection, as well as the ethics of end-of-life decision-making in
neurocritical care.
PMID- 29961422
TI - Recurrence quantification analysis of resting state EEG signals in autism
spectrum disorder - a systematic methodological exploration of technical and
demographic confounders in the search for biomarkers.
AB - BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with
a worldwide prevalence of 1-2%. In low-resource environments, in particular,
early identification and diagnosis is a significant challenge. Therefore, there
is a great demand for 'language-free, culturally fair' low-cost screening tools
for ASD that do not require highly trained professionals. Electroencephalography
(EEG) has seen growing interest as an investigational tool for biomarker
development in ASD and neurodevelopmental disorders. One of the key challenges is
the identification of appropriate multivariate, next-generation analytical
methodologies that can characterise the complex, nonlinear dynamics of neural
networks in the brain, mindful of technical and demographic confounders that may
influence biomarker findings. The aim of this study was to evaluate the
robustness of recurrence quantification analysis (RQA) as a potential biomarker
for ASD using a systematic methodological exploration of a range of potential
technical and demographic confounders. METHODS: RQA feature extraction was
performed on continuous 5-second segments of resting state EEG (rsEEG) data and
linear and nonlinear classifiers were tested. Data analysis progressed from a
full sample of 16 ASD and 46 typically developing (TD) individuals (age 0-18
years, 4802 EEG segments), to a subsample of 16 ASD and 19 TD children (age 0-6
years, 1874 segments), to an age-matched sample of 7 ASD and 7 TD children (age 2
6 years, 666 segments) to prevent sample bias and to avoid misinterpretation of
the classification results attributable to technical and demographic confounders.
A clinical scenario of diagnosing an unseen subject was simulated using a leave
one-subject-out classification approach. RESULTS: In the age-matched sample,
leave-one-subject-out classification with a nonlinear support vector machine
classifier showed 92.9% accuracy, 100% sensitivity and 85.7% specificity in
differentiating ASD from TD. Age, sex, intellectual ability and the number of
training and test segments per group were identified as possible demographic and
technical confounders. Consistent repeatability, i.e. the correct identification
of all segments per subject, was found to be a challenge. CONCLUSIONS: RQA of
rsEEG was an accurate classifier of ASD in an age-matched sample, suggesting the
potential of this approach for global screening in ASD. However, this study also
showed experimentally how a range of technical challenges and demographic
confounders can skew results, and highlights the importance of probing for these
in future studies. We recommend validation of this methodology in a large and
well-matched sample of infants and children, preferably in a low- and middle
income setting.
PMID- 29961423
TI - Estimating the prevalence of schistosomiasis japonica in China: a serological
approach.
AB - BACKGROUND: The prevalence of schistosomiasis japonica has decreased
significantly, and the responses changing from control to elimination in Jiangsu
Province, P.R. China. How to estimate the change in prevalence of schistosomiasis
using only serological data will be important and useful. METHODS: We collected
serum samples from 2011 to 2015 to build a serum bank from Dantu County of
Jiangsu, China. Serum samples were detected by enzyme-linked immunosorbent assay
(ELISA), the positive rate and optical density (OD) value were obtained. The
Bayesian model including the prior information of sensitivity and specificity of
ELISA was established, and the estimated infection rates were obtained for
different years, genders and age groups. RESULTS: There was no significant
difference in the mean OD between different years and genders, but there was a
significant difference between the different age groups. There were statistically
significant differences in the positive rate for different years and age groups,
but no significant difference at different genders. The estimated infection rate
for the five years was 1.288, 1.456, 1.032, 1.485 and 1.358%, respectively. There
was no significant difference between different years and between genders, but a
significant difference between different age groups. CONCLUSIONS: The risk of
schistosomiasis transmission in this area still exists, and risk monitoring of
schistosomiasis should be strengthened.
PMID- 29961424
TI - Non-contrast assessment of microvascular integrity using arterial spin labeled
cardiovascular magnetic resonance in a porcine model of acute myocardial
infarction.
AB - BACKGROUND: Following acute myocardial infarction (AMI), microvascular integrity
and function may be compromised as a result of microvascular obstruction (MVO)
and vasodilator dysfunction. It has been observed that both infarcted and remote
myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns
associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR
is a novel non-contrast technique that can quantitatively measure MBF. This study
investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in
swine. METHODS: Thirty-one swine were included in this study. Resting ASL-CMR was
performed on 24 healthy swine (baseline group). A subset of 13 swine from the
baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen
swine were subjected to a 90-min left anterior descending (LAD) coronary artery
occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1-2
days (N = 9, of which 6 were from the baseline group), 1-2 weeks (N = 8, of which
4 were from the day 1-2 group), and 4 weeks (N = 4, of which 2 were from the week
1-2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were
performed post-AMI for reference. RESULTS: At rest, regional MBF and
physiological noise measured from ASL-CMR were 1.08 +/- 0.62 and 0.15 +/- 0.10
ml/g/min, respectively. Regional MBF increased to 1.47 +/- 0.62 ml/g/min with
dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in
the infarcted region 1-2 days, 1-2 weeks, and 4 weeks post-AMI compared to
baseline (P < 0.03). This was consistent with perfusion deficit seen on first
pass CMR and with MVO seen on LGE. There were no significant differences between
measured MBF in the remote regions pre and post-AMI (P > 0.60). CONCLUSIONS: ASL
CMR can assess vasodilator response in healthy swine and detect significant
reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to
gadolinium-based techniques for assessment of MVO and microvascular integrity
within infarcted, as well as salvageable and remote myocardium. This has the
potential to provide early indications of adverse remodeling processes post
ischemia.
PMID- 29961425
TI - The risk factors of vertebral refracture after kyphoplasty in patients with
osteoporotic vertebral compression fractures: a study protocol for a prospective
cohort study.
AB - BACKGROUND: Percutaneous kyphoplasty (PKP) is the first-line treatment for
osteoporotic vertebral compression fractures (OVCFs) that can immediately relieve
pain and allow the quick recovery of lost mobility. However, some studies
reported that after PKP, the incidence of vertebral refracture, particularly
adjacent vertebral fracture (AVF), was high. Our previous meta-analysis suggested
that the risks for vertebral refracture and AVF did not increase after
percutaneous vertebral augmentation in OVCF patients. Despite the negative
results of our meta-analysis, there is still significant evidence regarding the
relationship between kyphoplasty and AVF, so a new prospective cohort study is
warranted. In addition, in our previous retrospective study, we found that
advanced age, female sex and low oestradiol (E2) concentrations might be related
to the occurrence of postoperative vertebral refracture after PKP. To
sufficiently evaluate the probable factors involved in the occurrence of
postoperative vertebral refracture, we designed this prospective study. METHODS:
This is a prospective cohort study of patients admitted for PKP to treat painful
OVCFs. The baseline data, including demographic information, lifestyle, bone
metabolic status, sex hormone and sex hormone-binding globulin (SHBG) levels, and
clinical characteristics will be collected at the time of enrolment. Surgical
features of PKP will be recorded on the operation day. Lifestyle, bone metabolic
status, sex hormone levels, and SHBG levels will be assessed during the follow-up
period at 1 m, 3 m, 12 m, and 24 m postoperatively. Patients suffering from
acutely aggravated back pain will be referred to an orthopaedist, and refractured
vertebrae will be confirmed by magnetic resonance imaging and computed
tomography. The primary outcome will be the incidence of vertebral refracture.
Multivariate analyses will be carried out to evaluate the variables that are
independently correlated with vertebral refracture. DISCUSSION: To evaluate the
risk of postoperative refracture preoperatively and to identify the surgical
points related to postoperative refracture, this study will explore the risk
factors related to vertebral refracture after PKP. The results may provide new
information about defining OVCF patients suitable for PKP treatment. TRIAL
REGISTRATION: ChiCTR-ROC-17011562 . Registered on July 4th, 2017.
PMID- 29961426
TI - Marijuana promotions on social media: adolescents' views on prevention
strategies.
AB - BACKGROUND: Youth exposure to positive marijuana messages increases their risk of
marijuana use. Since Washington State legalized recreational marijuana in 2012,
marijuana businesses have used social media business pages to promote their
products. Regulations to prevent youth access and targeting by marijuana
businesses on social media in Washington State are absent. The purpose of this
study was to engage youth in conceptualizing prevention approaches to limit youth
exposure to marijuana business promotions on social media. METHODS: Towards our
goal of generating novel prevention approaches and promoting youth interaction to
build ideas, we used focus groups. Adolescents ages 15-20 years in Washington
State were recruited through purposeful sampling to achieve a diverse sample from
six schools across two counties. During focus groups, trained facilitators used a
semi-structured guide to prompt discussion about marijuana business presence on
social media. In the latter half of focus groups, facilitators showed example
social media posts from marijuana businesses. All focus groups were audio
recorded and manually transcribed. Qualitative analysis was conducted using the
constant comparative method. RESULTS: A total of 32 adolescents with average age
17 years (SD = 0.6), 71% female, 43.8% Asian and 21.9% mixed race, participated
in 5 focus groups. Recommendations for prevention focused in two main thematic
areas. First, participants supported policies to restrict underage access to
marijuana social media pages, an example quote was: "you have access to [the
social media page] without being 21 and I think that's a problem." Second,
participants proposed regulation of content that marijuana companies can post on
social media, an example quote was: "I'm thinking they shouldn't be allowed to
use children or anything associated with children and the memes that they post."
CONCLUSIONS: Our findings indicate two strategies to limit youth exposure to
marijuana content on social media. These specific strategies represent potential
avenues to revise state policies and test the effectiveness of these approaches
for states that permit recreational marijuana.
PMID- 29961427
TI - Unusual case of primary spontaneous hemopneumothorax in a young man with atypical
tension pneumothorax: a case report.
AB - BACKGROUND: Spontaneous life-threatening hemopneumothorax is an atypical but
treatable entity of unexpected circulatory collapse in young patients, affecting
0.5-11.6% of patients with primary spontaneous pneumothorax. Spontaneous
pneumothorax is a well-documented disorder with a classic clinical presentation
of acute onset chest pain and shortness of breath. This disorder might be
complicated by the development of hemopneumothorax or tension pneumothorax. CASE
PRESENTATION: A 23-year-old Asian man was referred to the emergency room of
Xiamen Chang Gung Memorial Hospital with a 1-day history of right-sided chest
pain that had been aggravated for 1 hour. A physical examination revealed a young
man who was awake and alert but in mild to moderate painful distress. His vital
parameters were relatively stable at first. The examining physician noted slight
tenderness along the right posterolateral chest wall along the eighth and tenth
ribs. Primary spontaneous pneumothorax was considered, and a standing chest X-ray
confirmed the diagnosis. A right thoracostomy tube was immediately placed under
sterile conditions, and he was referred to the respiratory service. While in the
respiratory department, approximately 420 mL of blood was drained from the
thoracostomy tube over 15 minutes. Our patient developed obvious hemodynamic
instability with hypovolemic shock and was subsequently admitted to the
cardiothoracic surgical ward after fluid resuscitation. During the ensuing 4
hours after admission, 750 mL of blood was drained through the thoracostomy tube.
A bedside chest X-ray was requested after he was temporarily hemodynamically
stabilized. Primary spontaneous hemopneumothorax associated with right tension
pneumothorax was considered based on the radiological impression and clinical
signs. An emergency limited posterolateral thoracotomy was performed. A standing
chest X-ray performed on day 6 of admission after the removal of the thoracostomy
tube showed a complete re-expansion of his right lung. He remained stable and was
discharged within 1 week. CONCLUSIONS: The successful treatment of a large
spontaneous hemopneumothorax depends on early recognition, proactive
intervention, and early consideration by a cardiothoracic surgeon. Once the
diagnosis is confirmed, early thoracotomy should be considered. Such an
aggressive surgery not only leads to shorter hospitalization but also confers
better long-term outcomes.
PMID- 29961428
TI - Activity of translation regulator eukaryotic elongation factor-2 kinase is
increased in Parkinson disease brain and its inhibition reduces alpha synuclein
toxicity.
AB - Parkinson disease (PD) is the second most common neurodegenerative disorder and
the leading neurodegenerative cause of motor disability. Pathologic accumulation
of aggregated alpha synuclein (AS) protein in brain, and imbalance in the
nigrostriatal system due to the loss of dopaminergic neurons in the substantia
nigra- pars compacta, are hallmark features in PD. AS aggregation and propagation
are considered to trigger neurotoxic mechanisms in PD, including mitochondrial
deficits and oxidative stress. The eukaryotic elongation factor-2 kinase (eEF2K)
mediates critical regulation of dendritic mRNA translation and is a crucial
molecule in diverse forms of synaptic plasticity. Here we show that eEF2K
activity, assessed by immuonohistochemical detection of eEF2 phosphorylation on
serine residue 56, is increased in postmortem PD midbrain and hippocampus.
Induction of aggressive, AS-related motor phenotypes in a transgenic PD M83 mouse
model also increased brain eEF2K expression and activity. In cultures of
dopaminergic N2A cells, overexpression of wild-type human AS or the A53T mutant
increased eEF2K activity. eEF2K inhibition prevented the cytotoxicity associated
with AS overexpression in N2A cells by improving mitochondrial function and
reduced oxidative stress. Furthermore, genetic deletion of the eEF2K ortholog efk
1 in C. elegans attenuated human A53T AS induced defects in behavioural assays
reliant on dopaminergic neuron function. These data suggest a role for eEF2K
activity in AS toxicity, and support eEF2K inhibition as a potential target in
reducing AS-induced oxidative stress in PD.
PMID- 29961430
TI - Cultural influences on the developing semantic lexicon.
AB - To determine whether the developing semantic lexicon varies with culture, we
examined the animal and food naming of children from three communities
distinguished by language, cultural heritage, and population density. The
children were five- and seven-year-olds from Australia (n = 197), Taiwan (n =
456), and the US (n = 172). Naming patterns revealed hierarchical and flexible
organization of the semantic lexicon. The content of the lexicon, particularly
food names, varied with cultural heritage. In all three communities, wild mammals
were predominant during animal naming, a likely influence of children's media.
The influence of the Chinese zodiac was evident in the clustering of animal names
in the Taiwanese sample. There was no apparent influence of population density
and little influence of language, except that the Taiwanese children more
frequently named foods at the superordinate level, a possible influence of the
structure of Mandarin. Children develop their lexicons in response to culture as
experienced first-hand or through media.
PMID- 29961429
TI - Modeling the elevated risk of yellow fever among travelers visiting Brazil, 2018.
AB - BACKGROUND: Unlike the epidemic of yellow fever from 2016 to 17 in Brazil mostly
restricted to the States of Minas Gerais and Espirito Santo, the epidemic from
2017 to 18 mainly involved Sao Paulo and Rio de Janeiro and resulted in multiple
international disseminations. To understand mechanisms behind this observation,
the present study analyzed the distribution of imported cases from Brazil, 2018.
METHODS: A statistical model was employed to capture the risk of importing yellow
fever by returning international travelers from Brazil. We estimated the relative
risk of importation among travelers by the extent of wealth measured by GDP per
capita and the relative risk obtained by random assignment of travelers'
destination within Brazil by the relative population size. RESULTS: Upper-half
wealthier countries had 2.1 to 3.4 times greater risk of importation than
remainders. Even among countries with lower half of GDP per capita, the risk of
importation was 2.5 to 2.8 times greater than assuming that the risk of
travelers' infection within Brazil is determined by the regional population size.
CONCLUSIONS: Travelers from wealthier countries were at elevated risk of yellow
fever, allowing us to speculate that travelers' local destination and behavior at
high risk of infection are likely to act as a key determinant of the
heterogeneous risk of importation. It is advised to inform travelers over the
ongoing geographic foci of transmission, and if it appears unavoidable to visit
tourist destination that has the history of producing imported cases, travelers
must be strongly advised to receive vaccination in advance.
PMID- 29961431
TI - Genome-wide study to detect single nucleotide polymorphisms associated with
visceral and subcutaneous fat deposition in Holstein dairy cows.
AB - Excessive abdominal fat might be associated with more severe metabolic disorders
in Holstein cows. Our hypothesis was that there are genetic differences between
cows with low and high abdominal fat deposition and a normal cover of
subcutaneous adipose tissue. The objective of this study was to assess the
genetic basis for variation in visceral adiposity in US Holstein cows. The study
included adult Holstein cows sampled from a slaughterhouse (Green Bay, WI, USA)
during September 2016. Only animals with a body condition score between 2.75 and
3.25 were considered. The extent of omental fat at the level of the insertion of
the lesser omentum over the pylorus area was assessed. A group of 100 Holstein
cows with an omental fold <5 mm in thickness and minimum fat deposition
throughout the entire omentum, and the second group of 100 cows with an omental
fold ?20 mm in thickness and with a marked fat deposition observed throughout the
entire omentum were sampled. A small piece of muscle from the neck was collected
from each cow into a sterile container for DNA extraction. Samples were submitted
to a commercial laboratory for interrogation of genome-wide genomic variation
using the Illumina BovineHD Beadchip. Genome-Wide association analysis was
performed to test potential associations between fat deposition and genomic
variation. A univariate mixed linear model analysis was performed using genome
wide efficient mixed model association to identify single nucleotide
polymorphisms (SNPs) significantly associated with variation in a visceral fat
deposition. The chip heritability was 0.686 and the estimated additive genetic
and residual variance components were 0.427 and 0.074, respectively. In total, 11
SNPs defining four quantitative trait locus (QTL) regions were found to be
significantly associated with visceral fat deposition (P<0.00001). Among them,
two of the QTL were detected with four and five significantly associated SNPs,
respectively; whereas, the QTLs detected on BTA12 and BTA19 were each detected
with only one significantly associated SNP. No enriched gene ontology terms were
found within the gene networks harboring these genes when supplied to DAVID using
either the Bos taurus or human gene ontology databases. We conclude that
excessive omental fat in Holstein cows with similar body condition scores is not
caused by a single Mendelian locus and that the trait appears to be at least
moderately heritable; consequently, selection to reduce excessive omental fat is
potentially possible, but would require the generation of predicted transmitting
abilities from larger and random samples of Holstein cattle.
PMID- 29961432
TI - Functional outcome after long-term low-dose trimethoprim/sulfamethoxazole in
chronic rhinosinusitis with purulence: a prospective study.
AB - OBJECTIVE: Trimethoprim/sulfamethoxazole has been suggested as a treatment option
for chronic rhinosinusitis with purulence. This study aimed to assess the
functional and endoscopic outcomes after a three-month course of low-dose
trimethoprim/sulfamethoxazole. METHODS: A prospective study was performed,
comprising patients referred to a tertiary care medical centre with a diagnosis
of chronic rhinosinusitis with purulence. Trimethoprim/sulfamethoxazole was
prescribed at 960 mg/day for three months. Sinonasal complaints and endoscopic
findings were documented, and bacteriological data were compared. RESULTS:
Fifteen patients were included. Staphylococcus aureus was the most common
bacterium cultured (86 per cent). Improvement in nasal function, as measured by
the 22-item Sino-Nasal Outcome Test, was highly significant at three months (p <
0.0005). This improvement slightly decreased but remained significant at 6, 9 and
12 months. No side effects were noted. Endoscopic scores revealed similar and
concordant improvements. CONCLUSION: Long-term low-dose
trimethoprim/sulfamethoxazole therapy seems to be a safe option for selected
patients. Additional randomised multicentre studies remain necessary.
PMID- 29961433
TI - Smokers' knowledge and perception of electronic cigarettes (e-cigarettes): a
qualitative study of non-quitting smokers in a North London general practice.
AB - BACKGROUND: The introduction of electronic cigarettes (e-cigarettes) has provided
smokers with an alternative source of nicotine. Interest and use of the device
has increased exponentially in the last decade with an estimated 2.9 m adult
users in Great Britain. Research so far on the attitudes and perceptions of
smokers to this new product has largely focussed on the views of current e
cigarette users, smokers attempting to quit and former cigarette smokers.AimThis
study aimed to explore the views of current tobacco smokers who were not using e
cigarettes and not looking for a cessation method, their understanding and
knowledge of e-cigarettes, and their views of e-cigarettes as a smoking cessation
aid provided by the National Health Service (NHS). METHODS: Semi-structured in
depth interviews were conducted with 14 patients from a general practice in North
London, who smoked conventional tobacco cigarettes on a daily or weekly basis,
over 18 years old. An iterative approach allowed for constant data analysis using
a thematic approach throughout the data collection stage, and generated four
recurring themes.FindingsE-cigarettes were primarily seen as a smoking cessation
device, with the supply of nicotine viewed as a benefit helping to reduce
withdrawal symptoms, although for some participants this supply could also be a
hindrance to dealing with their addiction. Despite uncertainty about the
components, e-cigarettes were mostly viewed as healthier due to their lack of
carcinogens, tar and smoke inhalation. The lack of reliable information and
strong evidence for both the effectiveness and the safety of e-cigarettes led
participants to be apprehensive about their provision by the NHS, and acted as a
barrier to their use as an aid to quitting. The recurring appeal for more
information regarding e-cigarettes make it clear that further high-quality
research is urgently needed in this field to provide reliable and accurate
information to smokers.
PMID- 29961434
TI - Management of locally advanced T3-4 glottic laryngeal carcinomas.
AB - OBJECTIVES: To assess five-year local control and ultimate local control rates of
patients treated for locally advanced T3-4 glottic carcinoma with surgery only,
radiotherapy only, or surgery plus radiotherapy. Cancer-specific survival,
overall survival and rates of malignancy development were also assessed. METHODS:
A retrospective review was conducted on patients from 1967 to 2015, with analysis
of local control, ultimate local control, overall survival and cancer-specific
survival performed using Kaplan-Meier and Cox regression. RESULTS: Of 169
eligible patients, the majority (59 per cent) were treated with surgery plus
radiotherapy, with laryngectomy being the most common surgical procedure. Local
control and ultimate local control rates were higher with surgery only (94.1 per
cent) and surgery plus radiotherapy (87.9 and 86.8 per cent respectively),
compared to radiotherapy only (46.8 and 52.4 per cent) (both p < 0.001). Cancer
specific survival, overall survival and malignancy development did not differ
between groups. CONCLUSION: Surgery, with or without radiotherapy, offers
significantly higher five-year local control and ultimate local control for
patients with advanced glottic carcinoma, compared to radiotherapy only.
PMID- 29961435
TI - Cost-effectiveness of three different strategies for the treatment of first
recurrent Clostridium difficile infection diagnosed in a community setting.
AB - OBJECTIVE: A significant portion of patients with Clostridium difficile
infections (CDI) experience recurrence, and there is little consensus on its
treatment. With the availability of newer agents for CDI and the added burdens of
recurrent disease, a cost-effectiveness analysis may provide insight on the most
efficient use of resources. DESIGN: A decision-tree analysis was created to
compare the cost-effectiveness of 3 possible treatments for patients with first
CDI recurrence: oral vancomycin, fidaxomicin, or bezlotoxumab plus vancomycin.
The model was performed from a payer's perspective with direct cost inputs and a
timeline of 1 year. A systematic review of literature was performed to identify
clinical, utility, and cost data. Quality-adjusted life years (QALY) and
incremental cost-effectiveness ratios were calculated. The willingness-to-pay
(WTP) threshold was set at $100,000 per QALY gained. The robustness of the model
was tested using one-way sensitivity analyses and probabilistic sensitivity
analysis. RESULTS: Vancomycin had the lowest cost ($15,692) and was associated
with a QALY gain of 0.8019 years. Bezlotoxumab plus vancomycin was a dominated
strategy. Fidaxomicin led to a higher QALY compared to vancomycin, at an
incremental cost of $500,975 per QALY gained. Based on our WTP threshold,
vancomycin alone was the most cost-effective regimen for treating the first
recurrence of CDI. Sensitivity analyses demonstrated the model's robustness.
CONCLUSIONS: Vancomycin alone appears to be the most cost-effective regimen for
the treatment of first recurrence of CDI. Fidaxomicin alone led to the highest
QALY gained, but at a cost beyond what is considered cost-effective.
PMID- 29961436
TI - Operational burden of implementing Salmonella Enteritidis and Typhimurium cluster
detection using whole genome sequencing surveillance data in England: a
retrospective assessment.
AB - Since April 2014 all presumptive Salmonella isolates received by Public Health
England (PHE) have been characterised using whole genome sequencing (WGS) and the
genomic data generated used to identify clusters of infection. To inform the
implementation and development of a national gastrointestinal infection
surveillance system based on WGS we have retrospectively identified genetically
related clusters of Salmonella Enteritidis and Salmonella Typhimurium infection
over a one year period and determined the distribution of these clusters by PHE
operational levels. Using a constrained WGS cluster definition based on single
nucleotide polymorphism distance, case frequency and temporal spread we
demonstrate that the majority of clusters spread to multiple PHE operational
levels. The greatest investigative burden is on national level staff
investigating small, geographically dispersed clusters. We also demonstrate that
WGS identifies long-running, slowly developing clusters that may previously have
remained undetected. This analysis also indicates likely increased workload for
local health protection teams and will require an operational strategy to balance
limited human resources with the public health importance of investigating small,
geographically contained clusters of highly related cases. While there are
operational challenges to its implementation, integrated cluster detection based
on WGS from local to international level will provide further improvements in the
identification of, response to and control of clusters of Salmonella spp. with
public health significance.
PMID- 29961437
TI - Promoting an action plan for devices in the emergency department-does it impact
catheter duration?
PMID- 29961438
TI - Comparison of basal lamella relaxing incision and combined conventional
medialisation and controlled synechiae in functional endoscopic sinus surgery: a
randomised prospective study.
AB - OBJECTIVES: To compare combined conventional Freer medialisation and controlled
synechiae, performed for middle meatal access (during the initial steps of
functional endoscopic sinus surgery) and post-operative middle turbinate
medialisation, with basal lamella relaxing incision, the latter of which is a
single step for achieving both middle meatal access and post-operative
medialisation. The study also compared the effects of controlled synechiae and
basal lamella relaxing incision on post-operative olfaction. METHOD: A randomised
prospective study was performed on 52 nasal cavity sides (32 patients). Only
basal lamella relaxing incision was performed in one group, and both conventional
medialisation and controlled synechiae were performed in the other. Intra
operative and post-operative photography was used to measure the middle meatal
area. A pocket smell test was used to assess olfaction. RESULTS: There were no
significant differences in operative middle meatal access and post-operative
medialisation of the middle turbinate. Post-operative olfaction was affected more
in the combined conventional medialisation and controlled synechiae group,
compared to the basal lamella relaxing incision group, but this finding was not
statistically significant. CONCLUSION: Basal lamella relaxing incision is an
effective single-step technique for achieving adequate middle meatal access and
post-operative medialisation, with no significant effect on olfaction.
PMID- 29961439
TI - Screening of cell surface properties of potential probiotic lactobacilli isolated
from human milk.
AB - Evaluation of eleven candidate probiotic Lactobacillus strains isolated from
human milk showed that some of the strains were well endowed with desirable cell
surface and attachment attributes. The cell surface properties (hydrophobicity,
auto-aggregation, attachment to collagen and HT-29 monolayer) of probiotic
Lactobacillus species of human milk origin were compared with reference
probiotic/ non-probiotic species and pathogenic strains. The bacterial adhesion
to hydrocarbons (BATH) was determined using three aliphatic (Chloroform, n-Hexane
and n-Octane) and two aromatic (Toluene and Xylene) solvents. Maximum affinity of
Lactobacillus strains towards chloroform and toluene indicated the presence of
low electron acceptor/ acidic surface components on cell surface of most of the
strains. The highest value of per cent hydrophobicity was recorded with
chloroform in HM1 (L. casei) (97.10 +/- 3.35%) and LGG (98.92 +/- 1.24%). A
moderate auto-aggregation attribute was observed in all of our Lactobacillus
isolates. Only HM10, HM12 and HM13 exhibited comparatively enhanced precipitation
rate after 7 h of incubation period. The adhesion potential to collagen matrix
was highest in LGG (26.94 +/- 5.83%), followed by HM1 (11.07 +/- 3.54%) and HM9
(10.85 +/- 1.74%) whereas, on HT-29 cells, HM8 (14.99 +/- 3.61%), HM3 (13.73 +/-
1.14%) and HM1 (11.21 +/- 3.18%) could adhere effectively. In this manner, we
noticed that although the cell surface properties and adhesion prospective of
probiotic bacteria were strain dependent, five of our isolates viz. HM1, HM3,
HM8, HM9 and HM10 exhibited promising cell surface properties, which could be
further targeted as indigenous probiotic.
PMID- 29961440
TI - Differences in mortality between infections due to extended-spectrum-beta
lactamase-producing Klebsiella pneumoniae and Escherichia coli.
PMID- 29961441
TI - Spiking of intravenous bags does not cause time-dependent microbial
contamination: a preliminary report.
PMID- 29961442
TI - A pedometer-based walking intervention in 45- to 75-year-olds, with and without
practice nurse support: the PACE-UP three-arm cluster RCT.
AB - BACKGROUND: Guidelines recommend walking to increase moderate to vigorous
physical activity (MVPA) for health benefits. OBJECTIVES: To assess the
effectiveness, cost-effectiveness and acceptability of a pedometer-based walking
intervention in inactive adults, delivered postally or through dedicated practice
nurse physical activity (PA) consultations. DESIGN: Parallel three-arm trial,
cluster randomised by household. SETTING: Seven London-based general practices.
PARTICIPANTS: A total of 11,015 people without PA contraindications, aged 45-75
years, randomly selected from practices, were invited. A total of 6399 people
were non-responders, and 548 people self-reporting achieving PA guidelines were
excluded. A total of 1023 people from 922 households were randomised to usual
care (n = 338), postal intervention (n = 339) or nurse support (n = 346). The
recruitment rate was 10% (1023/10,467). A total of 956 participants (93%)
provided outcome data. INTERVENTIONS: Intervention groups received pedometers, 12
week walking programmes advising participants to gradually add '3000 steps in 30
minutes' most days weekly and PA diaries. The nurse group was offered three
dedicated PA consultations. MAIN OUTCOME MEASURES: The primary and main secondary
outcomes were changes from baseline to 12 months in average daily step counts and
time in MVPA (in >= 10-minute bouts), respectively, from 7-day accelerometry.
Individual resource-use data informed the within-trial economic evaluation and
the Markov model for simulating long-term cost-effectiveness. Qualitative
evaluations assessed nurse and participant views. A 3-year follow-up was
conducted. RESULTS: Baseline average daily step count was 7479 [standard
deviation (SD) 2671], average minutes per week in MVPA bouts was 94 minutes (SD
102 minutes) for those randomised. PA increased significantly at 12 months in
both intervention groups compared with the control group, with no difference
between interventions; additional steps per day were 642 steps [95% confidence
interval (CI) 329 to 955 steps] for the postal group and 677 steps (95% CI 365 to
989 steps) for nurse support, and additional MVPA in bouts (minutes per week) was
33 minutes per week (95% CI 17 to 49 minutes per week) for the postal group and
35 minutes per week (95% CI 19 to 51 minutes per week) for nurse support.
Intervention groups showed no increase in adverse events. Incremental cost per
step was 19p and L3.61 per minute in a >= 10-minute MVPA bout for nurse support,
whereas the postal group took more steps and cost less than the control group.
The postal group had a 50% chance of being cost-effective at a L20,000 per
quality-adjusted life-year (QALY) threshold within 1 year and had both lower
costs [-L11M (95% CI -L12M to -L10M) per 100,000 population] and more QALYs [759
QALYs gained (95% CI 400 to 1247 QALYs)] than the nurse support and control
groups in the long term. Participants and nurses found the interventions
acceptable and enjoyable. Three-year follow-up data showed persistent
intervention effects (nurse support plus postal vs. control) on steps per day
[648 steps (95% CI 272 to 1024 steps)] and MVPA bouts [26 minutes per week (95%
CI 8 to 44 minutes per week)]. LIMITATIONS: The 10% recruitment level, with lower
levels in Asian and socioeconomically deprived participants, limits the
generalisability of the findings. Assessors were unmasked to the group.
CONCLUSIONS: A primary care pedometer-based walking intervention in 45- to 75
year-olds increased 12-month step counts by around one-tenth, and time in MVPA
bouts by around one-third, with similar effects for the nurse support and postal
groups, and persistent 3-year effects. The postal intervention provides cost
effective, long-term quality-of-life benefits. A primary care pedometer
intervention delivered by post could help address the public health physical
inactivity challenge. FUTURE WORK: Exploring different recruitment strategies to
increase uptake. Integrating the Pedometer And Consultation Evaluation-UP (PACE
UP) trial with evolving PA monitoring technologies. TRIAL REGISTRATION: Current
Controlled Trials ISRCTN98538934. FUNDING: This project was funded by the
National Institute for Health Research (NIHR) Health Technology Assessment
programme and will be published in full in Health Technology Assessment; Vol. 22,
No. 37. See the NIHR Journals Library website for further project information.
PMID- 29961443
TI - Danish general practitioners' professional attention to children of parents with
depression.
AB - INTRODUCTION: Offspring of parents with depression has an increased risk of
experiencing somatic and psychiatric diseases. Early child support can reduce
this risk. This study aimed to describe general practitioners' (GPs) professional
attention to children of depressed patients. METHODS: This was a survey study. We
mailed ques-tion-naires to randomly selected Danish GPs. RESULTS: Among the 1,760
GPs invited, 890 (51%) partici-pated. Female GPs accounted for 45% of the
respondents and 41% of the total GP population (p = 0.02). Respondents were
younger than the mean GP population. A total of 94% of the GPs reported that
giving attention to children of de-pressed parents was relevant, and 65% reported
addressing the children's well-being during the consultation with the parent. A
total of 39% of the GPs found that their knowledge about the significance of
parental depression for the child was poor, and 41% were highly interested in
learning more. Female GPs perceived that they had sufficient knowledge (66%) more
frequently than male GPs (56%) (p < 0.001). GPs with sufficient perceived
knowledge addressed the children's well-being more frequently than GPs with poor
perceived knowledge (odds ratio = 5.8; 95% confidence interval: 4.14-8.07).
CONCLUSIONS: This study showed a significant, under-utilised potential for
improving GPs' awareness about children of parents with depression. Perceived
knowledge of the potential impact of parental depression was crucial for the
attention given to the children. FUNDING: The study was funded by The Central
Denmark Region and the Danish National Research Foundation for Primary Care.
TRIAL REGISTRATION: not relevant.
PMID- 29961444
TI - The applicability of guidelines on antimicrobials provided by the Danish Health
Authority.
AB - INTRODUCTION: Our objective was to investigate the know-ledge of "Guidelines on
prescribing antibiotics for physicians and others in Denmark" published by the
Danish Health Au-thority in 2012, and the usefulness of these guidelines for
Danish hospital doctors. METHODS: We collected information on the perceived aware
ness and usefulness of the guidelines using a ques-tionnaire distributed at two
regional hospitals. Furthermore, to evaluate the use of the guidelines, we
collected data about 310 patients treated with antimicrobials at the two
hospitals. RESULTS: Less than 50% of the respondents knew that the guidelines
existed and among those who did know of the existence of the guidelines, less
than 50% found that the guidelines were applicable to their daily clinical work.
Regarding sampling of microbiological tests, we found that in 188 of the 310
cases both urine and blood had been sampled. A discontinuation date was
registered in the medication module at the time of the prescription in 27% of the
prescriptions. In terms of reassessment, we evaluated 282 cases and found that a
reassessment had taken place in 62% of these cases. CONCLUSIONS: The results of
the survey indicate that knowledge and use of the guidelines are sparse, and our
data from the audits underline these data. FUNDING: The Fund for the Prevention
of Hospital-acquired Infections, the Danish Ministry of Health (R. no. 1406148)
and the Fund for Improving Skills in Infection Control, Central Denmark Region,
funded the study. TRIAL REGISTRATION: not relevant. The Danish Data Protection
Agency (R. no.: 1-16-02-84-15) and the Central Denmark Region approved the
project.
PMID- 29961445
TI - Have we reached the bottom of the bottomless pit- lessons from the recent lipid
lowering trials?
PMID- 29961446
TI - Incidence and predictors of perioperative myocardial infarction in patients
undergoing non-cardiac surgery in a tertiary care hospital.
AB - BACKGROUND: The stress in the perioperative period is compounded by unpredictable
and un-physiological changes in sympathetic tone, cardiovascular performance,
coagulation and inflammatory responses, all of which in turn lead to alterations
in plaque morphology predisposing to perioperative myocardial infarction (PMI).
PMI has a considerable morbidity and mortality in patients undergoing not only
high risk surgery, but also even with minor surgical interventions. OBJECTIVE: To
study the incidence of PMI and its predictors in patients undergoing non-cardiac
surgery in a tertiary care hospital. MATERIALS AND METHODS: Patients undergoing
non-cardiac surgery were included in this prospective single-center observational
study. The revised cardiac risk index (RCRI) was used for risk stratification.
ECG monitoring was done for all patients. For patients suggestive of acute
myocardial ischemia, echocardiography and serum troponin were evaluated. The
patient was labeled as having a PMI if there was raised troponin level along with
any one evidence of myocardial ischemia (symptoms, ECG changes or imaging
results) and in these patients the factors predisposing to PMI were evaluated.
All patients in the study were followed up to 30 days. RESULTS: Of the 525
patients analyzed, 33 patients (6.28%) had a PMI. Twelve out of the 33 (36.36%)
PMI patients died within 30 days following surgery. Patients undergoing high risk
surgery, smokers and patients with a past history of ischemic heart disease (IHD)
were found to be at higher risk of developing PMI. The ASA physical status
classification and the RCRI proved to be good predictors of PMI. Most of the PMI
events (72.7%) occurred within 48 hours of surgery. CONCLUSION: PMI is a dreaded
complication associated with a very high mortality. High risk surgery, smoking
and past history of ischemic heart disease were independent predictors of PMI.
The RCRI is a useful tool in pre-operative risk stratification of patients.
PMID- 29961447
TI - Pulse wave analyzed cardiovascular parameters in young first degree relatives of
type 2 diabetics- a cross-sectional study.
AB - BACKGROUND: First degree relatives (FDR) of type 2 diabetic (T2D) are predisposed
for type 2 diabetes mellitus (T2DM) which accelerates cardiovascular aging. Pulse
wave analysis (PWA) gives non-invasive measurement of central hemodynamics like
central blood pressure (cBP), cardiac output (CO), stroke work (SW) and vascular
stiffness like pulse wave velocity (PWV) and augmentation index at heart rate 75
(AIx@75). OBJECTIVE: To study PWA derived cardiovascular parameters in FDRs of
T2D as compared to controls. MATERIALS AND METHODS: We enrolled 117 FDRs of T2D
and 117 matched controls for a cross-sectional study. We performed PWA using
Mobil-o-Graph (IEM, Germany) by oscillometric method to derive cardiovascular
parameters which were compared and correlated for significance. P value less than
0.05 was considered statistically significant. RESULTS: Gender, age, height,
weight, body mass index (BMI), physical activity were comparable between groups.
FDRs of T2D had significantly higher blood pressure (brachial-systolic 125 vs
118, diastolic 80 vs 77, mean 100 vs 96mmHg and central- systolic 113 vs 105,
diastolic 82 vs 79, pulse pressure 31 vs 28mmHg), SW (98 vs 90gm/bt), rate
pressure product (RPP- 113 vs 107), PWV (5.14 vs 4.89m/s), AIx@75 (30 vs 27) than
control. Dependant variables correlated with brachial BP more than age or
anthropometric variables. Result did not differ by maternal or paternal
inheritance in case group. CONCLUSIONS: Young, sedentary, non-obese FDRs of T2D
have adverse cardiovascular profile which is suggested to worsen before or with
onset of T2DM and definitely need attention for life style modification as
primary prevention.
PMID- 29961448
TI - The association of plasma high-sensitivity C-reactive protein level with
rheumatic heart disease: The possible role of inflammation.
AB - BACKGROUND: Currently, it is not clear whether recurrent traumatic events lead to
progression of rheumatic heart disease (RHD) after the incident of acute
rheumatic fever or a persistent inflammatory state at the site of the valves. The
aim of this study was to assess the possible association between plasma high
sensitive C Reactive Protein (hs-CRP) level as an indicator of inflammation and
RHD. MATERIALS & METHODS: Ninety patients with RHD and 90 healthy controls who
had undergone complete echocardiographic examination were enrolled in this cross
sectional study. A score was given to each patient according to the severity of
valvular involvement. Plasma hs-CRP level was checked for each patient by ELISA
method twice with two-week interval, and the mean hs-CRP was calculated. RESULTS:
The mean plasma hs-CRP level in the case group was significantly higher compared
to its level in the control group (2.59+/-4.82 and 0.55+/-0.43 in the case and
control groups respectively, p<0.001). There was also a strong association
between the level of plasma hs-CRP and the severity of rheumatic valvular
involvement (p<0.001). CONCLUSION: The mean plasma hs-CRP level seems to have a
significant association with RHD and its severity. Further studies are needed to
determine the cause and effect relationship.
PMID- 29961449
TI - Physical activity levels of patients prior to acute coronary syndrome -
Experience at a tertiary care hospital in Sri Lanka.
AB - OBJECTIVES: Physical inactivity is associated with high cardiovascular risk. The
purpose of this study was to study physical activity levels of patients with
acute coronary syndrome (ACS). METHODOLOGY: A total of 504 patients, from the
Professorial Unit of the Colombo South Teaching Hospital completed the
International Physical Activity Questionnaire (IPAQ). IPAQ is a validated
questionnaire used internationally to objectively measure physical activity. Both
the total volume and the number of sessions of activity are included in the IPAQ.
Populations are divided into three levels based on physical activity levels: low,
moderate and high activity. RESULTS: Out of 504 patients, 128 (25.1%) were highly
active, 87 (17.1%) were minimally active and 289 (56.7%) were found be inactive.
When considering mets per week 134 (26.3%) spent less than 1000mets/week.
Physical activity levels of men and women were similar (p=0.06). There was a no
significant association between body mass index (BMI) with total IPAQ score
(p=0.11). There was no difference in the physical activity levels of patients
presenting with different types of ACS: ST-Elevation Myocardial Infarction
(STEMI), non-ST-elevation myocardial infarction (NSTEMI) or unstable angina (UA)
(p=0.36). The activity levels did not affect the severity of ACS assessed by
Thrombolysis In Myocardial Infarction (TIMI) scores. (NSTEMI/UA p=0.24, STEMI
p=0.10). CONCLUSION: In Sri Lanka, a majority of patients with ACS were
physically inactive. Physical inactivity is one of the remediable major risk
factors of ACS and an active life style should be promoted.
PMID- 29961450
TI - Efficacy of serum blood urea nitrogen, creatinine and electrolytes in the
diagnosis and mortality risk assessment of patients with acute coronary syndrome.
AB - BACKGROUND: Although blood urea nitrogen (BUN), creatinine (Cr) and electrolytes
are not the mainstay of diagnosis in acute coronary syndrome (ACS) patients but
they may have a role in providing a more detailed view of the complications and
mortality rates. The aim of this study was to determine the efficacy of these
parameters in the diagnosis and mortality risk-assessment of patients with ACS.
METHODOLOGY: A total of 200 patients with ACS were recruited in this prospective
study. The relationship of serum BUN, Cr and electrolytes with cardiac enzymes,
Global Registry of Acute Coronary Events (GRACE) and mortality was assessed
during a 6-months follow-up. Statistical test like multivariate linear regression
and binary logistic regression analysis were applied. RESULTS: On multivariate
linear regression analysis, serum potassium (K) (Unstandardized Coefficient B=
3.77; p=0.04) showed significant negative association with Creatine Kinease and
serum BUN (Unstandardized Coefficient B=0.52; p=0.001) showed significant
positive association with Troponin I. The patients with GRACE>105 had
significantly higher levels of serum BUN and Cr. Receiver operating
characteristic curves showed that area under curve (AUC) of BUN (0.7) was higher
than AUC of Cr (0.5). Multiple adjusted model showed that patients with
BUN>32.5mg/dl were almost 20 times more likely to be associated with mortality as
compared to reference group. CONCLUSION: In addition to cardiac enzymes, K along
with BUN and Cr may serve as important aid in diagnosis of ACS. BUN and Cr may
also serve as important tools in mortality-risk assessment of ACS patients.
PMID- 29961451
TI - Factors affecting seasonal changes in blood pressure in North India: A population
based four-seasons study.
AB - OBJECTIVE: There are no community based, longitudinal, intra individual
epidemiological studies on effect of weather and season on blood pressure (BP).
We evaluated the effect of season and temperature on prevalence and epidemiology
of BP in tropical climate. METHODS AND RESULTS: It was a longitudinal cross
sectional survey of rural and urban subjects in their native surroundings. BP was
measured in four different seasons in same subjects. A total of 978 subjects (452
rural and 521 urban) were included in the current analysis. Demographic
characteristics such as age, gender, education, occupational based physical
activity and body mass index (BMI) were recorded. Mean BP, both systolic and
diastolic were significantly higher in winter season as compared to summer
season. Mean difference between winter and summer was 9.01 (95% CI: 7.74-10.28,
p<0.001) in systolic BP and 5.61 (95% CI: 4.75-6.47, p<0.001) in diastolic BP.
This increase in BP was more marked in rural areas and elderly subjects.
Prevalence of hypertension was significantly higher during winter (23.72%) than
in summer (10.12%). CONCLUSION: BP increases significantly during winter season
as compared to summer season. Increase is more marked in rural areas and elderly
subjects. Seasonal variation in BP should be taken into account while looking at
prevalence of hypertension in epidemiological studies.
PMID- 29961452
TI - Is mitral annular ascent useful in studying left ventricular function through
left atrio-ventricular interactions?
AB - BACKGROUND: The mitral annulus (MA) is a crucial structure that is in constant
motion throughout the cardiac cycle. The main purpose of this study was to
determine if M-mode evaluation of the longitudinal motion of the MA could be
useful to examine atrio-ventricular interactions. METHODS: Echocardiographic data
obtained from 150 patients (mean age 56 +/- 16; 82 males) from the University of
Cincinnati College of Medicine was evaluated to examine if any relationship
exists between MA motion and measures of atrio-ventricular interactions. RESULTS:
Even though left atrial size, left ventricular (LV) mass index, LV ejection
fraction (LVEF) and degree of LV diastolic dysfunction (LVDD) were significant
echocardiographic variables affecting MA motion; LVEF and the degree of LVDD were
the main determinants of MA excursion during systole (MAPSE) and after atrial
contraction (MAa). Our results confirm the surrogate value of MAPSE with regards
to LVEF and also show that the extent of MA excursion during systole is the main
determinant of MAa. The effect of LV diastolic function applies more strongly to
MAPSE than to MAa. However, the maximal MAa amplitude varies in accordance to the
type of LVDD. CONCLUSIONS: We have shown for the first time that M-mode
interrogation of the MA longitudinal motion appears useful to assess atrio
ventricular interactions. Since LV systolic and diastolic functions are so
closely related; additional studies are now required to examine how this
longitudinal measure correlates with known circumferential rotational data
obtained with other imaging modalities.
PMID- 29961453
TI - Value of mitral annular plane systolic excursion in the assessment of contractile
reserve in patients with ischemic cardiomyopathy before cardiac
revascularization.
AB - BACKGROUND: Mitral annular plane systolic excursion (MAPSE) is an M-mode derived
echocardiographic marker of left ventricular longitudinal function, the aim of
this study is to evaluate the value of MAPSE in assessment of contractile reserve
in patients with ischemic cardiomyopathy before cardiac revascularization.
METHODS: The study included 50 patients with ischemic cardiomyopathy with
ejection fraction (EF) <=35%, the patients presented to echocardiography
laboratory for dobutamine stress echocardiography (DSE) to assess viability and
contractile reserve before revascularization, patients with primary valvular
disease, and those with significant mitral annular calcifications were excluded
from the study. A low dose DSE was done to all patients using standardized
incremental infusions of 5, 10, and 20 MUg/kg/min and the following parameters
were measured at both baseline and peak dose, (EF, wall motion score index(WMSI)
and MAPSE). Contractile reserve was measured as the difference between the low
dose and baseline values of the EF and WMSI. RESULTS: The study included 50
patients aged 55.08+/-7.15 years, 94% were males, the DSE protocol was complete
in all patients without serious side effects. A total of eight hundred segments
were analyzed, at baseline 65% were dysfunctional including 31.2% hypokinetic,
28.8% were akinetic, and 5% were dyskinetic. At low dose study 70% of the
dysfunctional myocardium showed viability, EF increased significantly from
30.84+/-4.56 to 42.24+/-8.15%, p <0.001, the WMSI reduced significantly from
1.92+/-0.33 to 1.47+/-0.39, and MAPSE increased significantly from 1.02+/-0.23 to
1.30+/-0.30mm. MAPSE showed a significant positive correlation with EF at both
baseline and low dose study (r=0.283, p=0.046 & r=0.348, p=0.013) respectively
and a significant negative correlation with WMSI at both baseline and low dose
study (r=-0.3, p=0.034 & r=-0.409, p=0.003), respectively. By ROC curve analysis
we found that Delta MAPSE >=2mm can predict contractile reserve at Delta EF >10%
(AUC=0.6, sensitivity 67.86, specificity 59.09), and Delta MAPSE >=1.8mm can
predict contractile reserve at DeltaWMSI <=0.20 (AUC=0.61, sensitivity 65.5,
specificity 75.6). CONCLUSIONS: MAPSE is a rapid simple quantitative
echocardiographic method that can asses contractile reserve in patients with
ischemic cardiomyopathy before cardiac revascularization.
PMID- 29961454
TI - The correlation between speckle tracking echocardiography and coronary artery
disease in patients with suspected stable angina pectoris.
AB - BACKGROUND: To examine the value of speckle tracking echocardiography to detect
the presence, extent and severity of coronary artery affection in patients with
suspected stable angina pectoris. METHODS: Two hundred candidates with suspected
stable angina pectoris and normal resting conventional echocardiography were
subjected to speckle tracking echocardiography and coronary angiography. Global
and segmental longitudinal peak systolic strain were assessed and were correlated
to the results of coronary angiography for each patient. RESULTS: There was a
statistically significant difference in the mean of global longitudinal peak
systolic strain between normal coronaries and different degrees of coronary
artery disease (CAD) (-20.11+/-0.8 for normal, -18.34+/-2.52 for single vessel,
16.14+/-2.85 for two vessels, -14.81+/-2.12 for three vessels, -13.01+/-2.92 for
left main disease). GLPSS showed high sensitivity for the diagnosis of single
vessel CAD (90%, specificity 95.1%, cutoff value: -18.44, AUC: 0.954); two
vessels disease (90%, sensitivity 88.9%, cutoff value -17.35, AUC: 0.906) and for
three vessels CAD (cutoff value -15.33, sensitivity 63% and specificity 72.2% AUC
0.681) segmental LPSS also showed statistical significance for localization of
the affected vessel for left anterior descending, left circumflex and right
coronary artery (rho=0.001) and inverse correlation with syntax score that was
significant with high and intermediate score (rho=0.001) and insignificant for
low syntax score (rho value 0.05). CONCLUSION: Two-dimensional speckle tracking
echocardiography has good sensitivity and specificity to predict the presence,
extent and severity of CAD.
PMID- 29961455
TI - Three-dimensional echocardiographic evaluation of mechanical dyssynchrony in
systolic heart failure with narrow QRS complex.
AB - OBJECTIVES: To investigate the role of three-dimensional echocardiography (3DE)
in evaluation of left ventricular mechanical dyssynchrony (LVMD) in heart failure
(HF) patients with narrow QRS. METHODS: 143 subjects (70 with HF and narrow QRS,
23 with HF and LBBB and 50 controls) were subjected to 3DE, evaluating global and
regional dyssynchrony using systolic dyssynchrony index, maximum segmental
dyssynchrony and opposite segment dyssynchrony. Spatial distribution of LVMD was
studied in each patient using 3DE derived regional time volume curves. Extent of
LVMD in HF patients with narrow QRS was compared to those with left bundle branch
block (LBBB). RESULTS: Frequency of LVMD was similar in HF patients with narrow
QRS or LBBB (55.7% vs. 47.8%, p=NS). There was no difference in the severity of
LVMD between these two groups (10.7+/-6.7% vs. 12.1+/-7.4%, p=NS). Both HF groups
had significantly more dyssynchrony than controls. A scattered pattern of
distribution of asynchronous segments was seen in narrow QRS patients; 33.96% of
them had their earliest contracting segment, instead of delayed segment, located
in areas conventionally targeted for LV pacing i.e. anterolateral, inferolateral
or inferior segments. CONCLUSIONS: 3DE confirmed significant dyssynchrony in >50%
HF patients with narrow QRS as demonstrated by other imaging methods. 3D
distribution patterns of asynchronous segments indicate possibility of left
ventricular mechanics related reasons responsible for lack of CRT responsiveness,
an observation that generates hypothesis on possible reasons of CRT non
responsiveness.
PMID- 29961456
TI - Long-term outcomes following left main bifurcation stenting in Indian population
Analysis based on SYNTAX I and II scores.
AB - BACKGROUND: Syntax 1 and recently Syntax 2 (SS2) scores are validated risk
prediction models in coronary disease. OBJECTIVES: To find out the long term
outcomes following stenting for unprotected left main bifurcation disease (LMD)
and to validate and compare the performance of the SYNTAX scores 1 and 2 (SS1 and
SS2 PCI) for predicting major adverse cardiac events (MACE) in Indian population.
METHODS: Single-center, retrospective, observational study involving patients who
underwent percutaneous coronary intervention (PCI) with at least one stent
implanted for the LMD. Discrimination and calibration models were assessed by ROC
curve and the Hosmer-Lemeshow test. RESULTS: Data of 103 patients were analyzed.
The mean SS1 and SS2 scores were 27.9 and 30.7 and MACE was 16.5% at 4 years. The
target lesion revascularization (TLR) rate at 4 years was 11(10.7%). There were 4
deaths (3.8%). The mean left ventricular ejection fraction (LVEF) was the only
variable in SS2, which predicted cardiac events. ROC curve analysis showed both
models to be accurate in predicting TLR and mortality following LM PCI. SS2 score
showed a better risk prediction than SSI with AUC for TLR (SSI 0.560 and SS2PCI
0.625) and AUC for mortality (SS1 0.674 and SS2PCI 0.833). Hosmer-Lemeshow test
validated the accuracy of both the risk models in predicting the events.
CONCLUSIONS: Both risk models were applicable for Indian patients. The SS2 score
was a better predictor for mortality and TLR. In the SS2 score, the LVEF was the
most useful predictor of events after LM PCI.
PMID- 29961457
TI - Predictors of contrast induced nephropathy and the applicability of the Mehran
risk score in high risk patients undergoing coronary angioplasty-A study from a
tertiary care center in South India.
AB - OBJECTIVE: To study the incidence and predictors of Contrast induced nephropathy
(CIN) in high risk patients undergoing coronary angioplasty. To study the
applicability of the Mehran Risk Score (MRS) in the prediction of CIN in our
population. METHODS: This was a prospective observational study where patients
with an estimated glomerular filtration rate (eGFR) between 30 and 60ml/mt
undergoing elective percutaneous coronary intervention (PCI) over a period of 15
months were evaluated prospectively for the development of CIN. The patients who
developed CIN were then analysed for the presence of specific risk factors. The
patients were categorized into the 4 risk groups based on the MRS. RESULTS: 100
high risk patients underwent PCI during the study period. The incidence of CIN
was 29%. On multivariate analysis, the presence of anemia (p=0.007), increased
contrast volume usage (as defined by >5* B.Wt/S.cr) (p=0.012) and usage of loop
diuretics (p=0.033) were independently found to confer a significant risk of CIN.
In patients belonging to the high Mehran risk group (MRS10- 15) and very high
risk group (MRS >15) the risk of CIN was 3 fold (OR: 3.055, 95% CI: 1.18-7.94,
p=0.022) and 24 fold (OR: 24, 95% CI: 2.53-228.28, p=0.006) higher respectively
when compared to intermediate and low risk patients (MRS <10). CONCLUSION: The
incidence of CIN in high risk patients undergoing PCI is substantially higher in
our population compared to similar studies in the west. The MRS risk prediction
is pertinent even in an Indian population.
PMID- 29961458
TI - Risk factors and angiographic profile of coronary slow flow (CSF) phenomenon in
North Indian population: An observational study.
AB - BACKGROUND: "Coronary slow flow'' (CSF) is delayed vessel opacification in the
absence of epicardial stenosis. Studies in different ethnic groups have found
variable risk factors associated with CSF. AIM: of present study was to analyze
the risk factors and angiographic profile of CSF in North Indian population, not
studied till date. METHODS: 40 patients with CSF and 40 controls were studied.
CSF was determined quantitatively by thrombolysis in myocardial infarction (TIMI)
frame count method. Various clinical risk factors (age, sex, body mass Index
(BMI), diabetes, hypertension, dyslipidemia, smoking), hematological and
biochemical parameters (hematocrit, platelet count, uric acid, homocysteine,
fibrinogen, high sensitivity C reactive protein (hsCRP), glycosylated hemoglobin
(HbA1c) were assessed. RESULTS: Of the 40 patients with CSF, 37 (92.5%) were
males. While 20 patients (50%) presented with chronic stable angina, rest 20
(50%) presented with acute coronary syndrome. [15 (37.5%) with unstable angina
and 5 (12.5%) with non ST elevation myocardial infarction (NSTEMI)]. Patients
with CSF had significantly higher BMI (27.27+/-2.82 vs. 24.12+/-2.35, p<0.001),
fibrinogen levels (398.48+/-120.96 vs. 331.55+/-162.6, p=0.04) and smoking
(24(60.0%) vs 14(35.0%), p=0.02). On multivariable regression analysis, only BMI
was found to have an independent association with CSF (odds ratio 1.613, 95%
confidence interval 1.265-2.057, p<0.001). CONCLUSION: This is the first study to
analyze clinical presentation, angiographic profile and risk factors associated
with CSF in North Indian population. In this study, we found only BMI to have an
independent association with CSF.
PMID- 29961459
TI - Reversal of premature ventricular complexes induced cardiomyopathy. Influence of
concomitant structural heart disease.
AB - BACKGROUND: We examined the effect of radiofrequency (RF) catheter ablation of
premature ventricular complexes (PVCs) on left ventricle (LV) function recovery
in patients with LV dysfunction, regardless the presence of structural heart
disease (SHD). METHODS: Seventy seven patients with impaired LV ejection fraction
(EF) (37.1+/-9.4), suspected to have PVCs cardiomyopathy (PVC-CM) (>10% PVCs
burden), referred for RF ablation were enrolled, and divided into 2 groups
according to the presence of SHD. SHD was ruled out by echocardiography, coronary
angiography or MRI. CARTO 3 mapping system was used employing activation mapping
in the majority of cases. Initial success was defined as complete elimination or
residual PVCs<=10 beats/30min. Long term success was defined as reduction in PVCs
burden >80% on follow-up holter. Echocardiography was done after 6 months.
Improvement of EF >5% was considered significant. RESULTS: Forty two (55.8%)
cases had SHD. PVCs burden was 28.4+/-9.8%. EF improved to 48.6+/-10.3. Initial
success, overall success, post procedural PVCs burden and EF were comparable in
both groups. EF improved in 47(75%) of successful cases with no significant
differences between both groups. Post-MI Patients were the least category to
improve. PVCs burden before and after ablation were the independent predictors of
LVEF recovery by multivariate analysis. Cutoff values of >18%, <8% had 100%
sensitivity and 85%, 87% specificity, respectively. CONCLUSIONS: PVCs elimination
by RF ablation results in significant improvement even restoration of LV function
regardless of PVC origin, or the presence of concomitant SHD. PVCs burden before
and after ablation are the main predictors of LVEF recovery.
PMID- 29961460
TI - Brugada syndrome in patients with acute febrile illness.
AB - BACKGROUND: Brugada syndrome (BrS) is an inherited electroclinical syndrome and
can be occasionally precipitated by fever. The prevalence of Brugada-type
electrocardiographic patterns (BTEP) due to febrile illnesses have not been
previously studied in India. MATERIALS AND METHODS: Between June 2014 and
December 2015, 525 consecutive patients admitted to a government hospital with
acute febrile illness were retrospectively enrolled. In addition to their
investigations for workup of fever, ECGs were analyzed and BTEP types 1 and 2
were noted. Daily ECGs if available were perused to document reversal. RESULTS:
BTEP was seen in 23 (4% 95%CI: 2.9-6.5%): BTEP type 1 (Brugada syndrome) in 11
patients (2%; 95%CI 1.2-3.7%) and BTEP type 2 in 12. All patients with BrS (BTEP
type1) were males; mean age and temperature were 37.7 years (SD: 17.6) and 38.8
degrees C (SD: 0.6), respectively. There were no significant differences in age,
temperature or ECG parameters between patients with BTEP and those without. These
patients neither had cardiac symptoms nor family history of sudden cardiac
deaths. Bacterial infections were the commonest cause of fever in patients with
BrS. All BTEP changes resolved with defervesence of fever except in one.
CONCLUSION: The prevalence of the fever induced BrS is higher in our study group
and is comparable to estimates in Southeast Asian populations. An ECG should be
considered in all febrile patients. Further studies are required for better
characterization and risk stratification of these patients.
PMID- 29961461
TI - Clinical profile in arrhythmogenic cardiomyopathy and a recessive plakophilin-2
gene mutation.
AB - OBJECTIVE: Arrhythmogenic cardiomyopathy (ACM) is not an uncommon cause of
cardiac morbidity in Kashmir valley. This study was designed to document various
clinical features and to sequence exons 11 and 12 of plakophilin 2 (PKP2) gene in
these patients. METHODS: ACM patients who attended cardiology outpatient
department of our institute from January 2014 to April 2015 were included in the
study. Their records were reviewed. Controls were randomly selected, who had no
history or family history of cardiac illness and had a normal cardiac
examination. A blood sample was also taken from both the groups for sequencing of
exon 11 and 12 of PKP2 gene. ACM patients were followed up until July 2016.
RESULTS: Eleven ACM patients and seven controls were included in the study. Most
common mode of presentation was ventricular tachycardia (VT). Two patients had
left ventricular (LV) systolic dysfunction. One patient had a splice site
mutation in exon 12 of PKP2 gene and one patient died during follow-up. One of
the controls had an intronic variation that has no pathogenic significance vis-a
vis ACM. CONCLUSION: Our study describes various clinical parameters in ACM
patients and a recessive plakophilin 2 mutation after a limited PKP2 gene
sequencing.
PMID- 29961462
TI - Profile of pulmonary embolism in service personnel posted at high altitude area.
AB - BACKGROUND: We evaluated the clinical presentation and risk factors of pulmonary
embolism (PE) in soldiers posted at high altitude areas (HAA). METHODS: We
conducted a retrospective analysis of all cases of PE presented to us between
March 2011 and Aug 2014. The patients were serving at an altitude between 10,000
and 22,000ft above sea level and PE was diagnosed using the pulmonary CT
angiography. Screening for the deep vein thrombosis (DVT) and procoagulant
conditions was done at presentation and after six months of treatment. The
patients were managed as per the American College of Cardiology (ACC) guidelines
and descriptive statistics were used to present the data. RESULTS: The patients
(53 males) had a mean age of 33+/-4.2 year and were serving at a mean altitude of
12,176+/-448 feet (ranged between 10,000 and 20,500) at the onset of symptoms.
Dyspnea (79%) and tachycardia (68%) were the commonest symptom and sign,
respectively. D dimer was positive in 96.2% of the cases while nonspecific T
inversion in the ECG was seen in 54.7% of the patients. Procoagulant work up
revealed a hereditary thrombophilic condition in 9 out of 53 patients. A total of
44 cases were idiopathic and DVT of lower limb veins was seen in 2 patients.
There was no mortality in our case series. CONCLUSION: PE is a common
complication of HAA and hereditary thrombophilia contributes in a minority of the
patients. Further studies are needed to ascertain the risk factors of PE at HAA.
PMID- 29961463
TI - Are cardiovascular risk parameters and glycemic levels associated with
periodontitis in type 2 diabetes patients? A clinical study.
AB - This study investigated the associations between cardiovascular risk parameters,
glycemic level and periodontitis in the diabetic adult population. BMI (body mass
index), total cholesterol and triglyceride was used as cardiovascular risk
measure and glycosylated hemoglobin (HbA1c) was recorded for glycemic levels.
Study results provide evidence of significant association between periodontal
disease, cardiovascular risk and glycemic levels.
PMID- 29961464
TI - Reperfusing the myocardium - a damocles Sword.
AB - Return of blood flow after periodic ischemia is often accompanied by myocardial
injury, commonly known as lethal reperfusion injury (RI). Experimental studies
have shown that 50% of muscle die of ischemia and another 50% die because of
reperfusion. It is characterized by myocardial, vascular, or electrophysiological
dysfunction that is induced by the restoration of blood flow to previously
ischemic tissue. This phenomenon reduces the efficiency of the present modalities
used to combat the ischemic myocardium. Moreover, despite an improved
understanding of the pathophysiology of this process and encouraging preclinical
trials of multiple agents, most of the clinical trials to prevent RI have been
disappointing and leaves us at ground zero to explore newer approaches.
PMID- 29961466
TI - Feasibility of ultra low-dose coronary computed tomography angiography.
AB - There is an urgent need to develop new protocols to reduce radiation dose of
coronary computed tomography angiography (CTA). The aim of this pilot study was
to demonstrate the feasibility of an ultra-low dose CTA scanning.
PMID- 29961467
TI - Intracoronary tenecteplase in STEMI with massive thrombus.
AB - Primary percutaneous coronary intervention is the current standard of care in ST
elevation myocardial infarction (STEMI). However, large thrombus is an
independent predictor for stent thrombosis and major adverse cardiac events in
patients undergoing primary angioplasty for STEMI. Here we report a series of
STEMI patients with large thrombus burden treated successfully with low dose
intracoronary thrombolysis. There was prompt and early ST resolution. There was
improvement in thrombolysis in myocardial infarction (TIMI) flow and myocardial
blush grade postlysis in all patients. Majority had recanalised infarct related
coronary artery thus obviating the need for stenting. There was no inhospital or
1 month mortality or bleeding events. Hence intracoronary thrombolysis is an
option in patients with large thrombus burden.
PMID- 29961465
TI - Post-truth era and cardiology: After ORBITA, before CABANA.
AB - The evidence-based medicine is rooted in the scientific truth. Oxford
Dictionaries has released its 2016 word of the year: "Post-truth," which they
define as "relating to or denoting circumstances in which objective facts are
less influential in shaping public opinion than appeals to emotion and personal
belief". In everything from climate change denial to the anti-vaccine movement,
we're seeing the consequences of a failure to engage with scientific evidence.
Fake news and post-truth pronouncements are increasingly common in social media
and political era and are unfortunately also progressively being applied to the
medical science. We also see some evidence of post-truth signals in daily
cardiology procedures and guidelines including both interventional cardiology and
cardiac electrophysiology. Guideline recommendations made before the randomized
controlled trials (RCT) are published might result in a scenario that the
interventions or procedures have been performed on millions of people, costing
billions of dollars, leading to unnecessary use of health care resources and
often, ending up being even accepted as routine procedures in certain clinical
situations. "Justice delayed is justice denied" is a legal cliche meaning that if
timely justice is not provided to the sufferer, it loses it importance and
violates human rights. In medicine, "The RCT delayed is justice denied", as
highlighted by ORBITA (Objective Randomised Blinded Investigation with optimal
medical Therapy of Angioplasty in stable angina) trial and as may happen with
CABANA (Catheter Ablation versus Anti-arrhythmic Drug Therapy for Atrial
Fibrillation Trial) in the post-truth era.
PMID- 29961468
TI - Percutaneous intervention for restoration of patency of occluded lower limb
arteriovenous dialysis access.
AB - BACKGROUND: Arteriovenous (AV) fistula thrombosis is a serious complication in
patients undergoing hemodialysis, often presenting with symptoms of venous
hypertension, failure to dialysis and uremic symptoms. Treatment is aimed to
provide symptomatic relief and to maintain hemodialysis access site patency. AIM:
To describe our initial experience in the endovascular treatment of lower limb AV
dialysis access (AV fistula) thrombosis and/or obstruction in patients undergoing
hemodialysis. SETTINGS AND DESIGN: This was a retrospective study carried out in
a tertiary care center. Study duration was 24 months. Follow-up was variable.
MATERIALS AND METHODS: Two patients with chronic kidney disease with stage 5
renal failure undergoing hemodialysis presented with lower limb arteriovenous
dialysis access (arteriovenous fistula) failure between July 2014 and September
2016. Both the patients underwent endovascular treatment and were analyzed
retrospectively. RESULTS AND CONCLUSION: Both the patient underwent successful
endovascular treatment for the failure of the lower limb AV dialysis access
thrombosis and/or obstruction. One patient had minimal dye extravasation during
manipulation of the guide wire, which ceased spontaneously. On follow-up, both
patients maintained patency of the dialysis access and are undergoing successful
hemodialysis. One patient had a recurrence of the thrombosis of the fistula at
9th month of the follow-up. Endovascular treatment was tried but we could not
succeed. However, we found endovascular treatment safe and effective in treating
AV fistula failures.
PMID- 29961470
TI - Stevia rebaudiana the unique medicinal plant with sweet taste having hypoglycemic
and hypolipidemic activities.
PMID- 29961469
TI - Takotsubo syndrome and coronary vasospasm: Two faces of the same coin?
PMID- 29961471
TI - Exercise based evaluations and rehabilitation in heart failure: An addendum to
the Cardiology Society of India's management protocols for chronic heart failure.
PMID- 29961472
TI - Authors reply: Stevia: Long term data is lacking!
PMID- 29961473
TI - Response to the editorial titled "BVS, RDN, IABP: The Afghanistan of
interventional clinical trials.
PMID- 29961474
TI - Authors reply: Exercise, but with caution!
PMID- 29961475
TI - Authors reply: Response to the editorial titled "BVS, RDN, IABP: The Afghanistan
of interventional clinical trials".
PMID- 29961477
TI - What determines the rejection of immigrants through an integrative model.
AB - This study tests different explanations of anti-immigrant attitudes through a
model that incorporates aspects of group conflict, social identity and intergroup
contact theories. Multigroup structural equation modelling was applied in three
surveys, which tracked the same indicators in no similar economic and migratory
contexts. In times of economic crisis, the perceived economic threat seems to
lead more to discrimination and rejection of immigrants (in line with Group
Conflict Theory), while sense of cultural threat is more likely to curb any
desire for coexistence with them. Both threats show to be affected by the
perceived size of the immigrant population, which increases the feeling of threat
in those traditionally favourable to immigration. Other explanatory factors were
also corroborated. Increasing contact with immigrants helps to lessen rejection,
especially in the case of cultural threat. Effects due to insecurity were less
marked and those relating to qualification were contrary to what was
hypothesized.
PMID- 29961478
TI - Predicting bias homicide across victim groups: A county-level analysis.
AB - Outside several notable exceptions, few studies have examined variations in bias
crime occurrences across American communities, and how community-level factors
may differentially shape violent and non-violent bias crimes across victim
groups. Drawing from ecological theories of crime, this study asks, (1) what are
the structural predictors of the likelihood of bias homicide occurrences? and (2)
how do structural predictors differ across bias victim groups? To answer these
questions, data on bias homicide are derived from the United States Extremist
Crime Database (ECDB) for the years 1990 through 2014 and paired with socio-
structural variables from the United States Census Bureau. Results are discussed
relative to the goals of understanding where fatal bias crimes are more likely to
occur as a means of informing law enforcement and policymakers interested in
preventing and responding to this specific form of crime.
PMID- 29961479
TI - Mental and physical health impairments at the transition to college: Early
patterns in the education-health gradient.
AB - Part of the education-health gradient may be related to inequalities in the
transition from high school to college by health impairment status. In this
paper, we use the National Longitudinal Survey of Youth 1997 to investigate the
link between health impairments beginning prior to high school completion and
college-going, distinguishing between individuals with mental, physical, or
multiple health impairments and between enrollment in 2-year and 4-year
postsecondary institutions. We find that individuals with mental impairments or
multiple impairments are less likely to initially enroll in 4-year postsecondary
institutions than individuals without health impairments, controlling on
background and high school preparation. We also find evidence that advanced math
course-taking in high school, an important step on the pathway to a 4-year
college for all students, does not provide students with mental impairments the
same return as students without health impairments. We discuss implications for
policy to address educational inequalities in health.
PMID- 29961480
TI - How far can the apple fall? Differences in teacher perceptions of minority and
immigrant parents and their impact on academic outcomes.
AB - While a large body of research has focused on increasing parental involvement in
schools, less work has considered teacher perceptions of parental involvement.
Teacher perceptions of parents are important because they influence teacher
practices and relationships with students, with ensuing consequences for student
outcomes. Prior research suggests that teacher perceptions of parents vary by
children's family background, but empirical work comparing teacher perceptions of
parental involvement across groups and the impact of such perceptions on
different student outcomes is lacking. Using nationally representative data from
the Education Longitudinal Study of 2002, we find that even after taking into
account parents' self-reported involvement in their adolescent children's
education, teachers are less likely to perceive that minority immigrant parents
are as involved as native-born White parents. Patterns also differ for teachers
of English and teachers of math in ways that are consistent with racial and
ethnic stereotypes about academic ability. Further, teacher perceptions of
parental involvement matter for student GPAs and teacher recommendations.
PMID- 29961481
TI - Educational attainment of transgender adults: Does the timing of transgender
identity milestones matter?
AB - Adolescence is a difficult life stage in which to navigate a transgender
identity, yet adolescence plays a key role in shaping educational trajectories.
While transgender-related stigma and victimization within secondary schools
persists, the social climate in which transgender adolescents navigate their
identity has changed over time. Analyzing data from the National Transgender
Discrimination Survey, a national, non-probability sample of U.S. transgender
adults, we address the following research questions: 1) Is experiencing
transgender identity milestones in adolescence associated with educational
attainment?; 2) Does this association vary by birth cohort? We find that those
who first experienced transgender identity milestones in adolescence attained
less education than those who first experienced milestones in other life stages.
This association is larger among younger birth cohorts, pointing to the
adolescent years as a particularly difficult time to navigate a transgender
identity, even in the midst of increased transgender awareness and resources
within schools and society.
PMID- 29961482
TI - Conflict thinking: Exploring the social basis of perceiving the world through the
lens of social conflict.
AB - Both human rights organisations and studies in political communication have
noticed an increasing use of conflict frames in contemporary politics within
Western societies. As such frames are only interesting for political actors if
they find resonance among a substantial share of the population, these
observations raise the question as to who supports conflict thinking and why?
Whereas public opinion research has studied many attitudes that are based on
conflict thinking (e.g., ethnic prejudice, populism, feelings of collective
deprivation, and welfare chauvinism), this paper addresses the more fundamental
question as to whether it is possible to measure people's general tendency to
perceive the world through the lens of social conflict. Data from the European
Quality of Life Survey (34,655 respondents; 34 countries) reveal strong
correlations between the perceptions of the amount of tension between seven pairs
of groups. These correlations are combined into a single scale reflecting the
amount of perceived social conflict in society. Subsequent multilevel analyses
support the claim that conflict thinking is embedded in different feelings of
vulnerability. In the conclusion, we elaborate on the implications of our
findings.
PMID- 29961483
TI - Perceived group cohesion versus actual social structure: A study using social
network analysis of egocentric Facebook networks.
AB - Research on group cohesion often relies on individual perceptions, which may not
reflect the actual social structure of groups. This study draws on social network
theory to examine the relationship between observable structural group
characteristics and individual perceptions of group cohesion. Leveraging Facebook
data, we extracted and partitioned the social networks of 109 participants into
groups using a modularity algorithm. We then surveyed perceptions of cohesion,
and computed group density and size using social network analysis. Out of six
linear mixed effects models specified, a random intercept and fixed slope model
with group size as a predictor of perceived group cohesion emerged as best
fitting. Whereas group density was not linked to perceived cohesion, size had a
small negative effect on perceived cohesion, suggesting that people perceive
smaller groups as more cohesive. We discuss the potential of social network
analysis, visualization tools, and Facebook data for advancing research on
groups.
PMID- 29961484
TI - Sexual identities and participation in liberal and conservative social movements.
AB - The desire for social change, political activism, and sexual identities may all
be related. Lesbians and gays generally contest heterosexism more than
heterosexuals but we do not know how sexual identities sways participation in
class, race, and gender based social movements. When analyzing the American
National Election Surveys of 2012 (n = 3519), gays and lesbians were about twenty
times more likely to join LGB justice campaigns than heterosexuals. Moreover, the
greater activism of gays and lesbians also crossed over to recent Occupy Wall
Street, peace, and environmental mobilizations. Finally, this analysis ends with
logistic regressions that determine if any sexual identity gaps in movement
participation are the result of demographic, contextual, and ideological
covariates.
PMID- 29961485
TI - Measuring religiosity in a religiously diverse society: The China case.
PMID- 29961486
TI - Group size and secular endogamy among the religiously unaffiliated in Canada.
AB - High religious intermarriage among the religiously unaffiliated is usually
interpreted as evidence of religion's minor importance for this group. Between
1981 and 2011, religious intermarriage among the unaffiliated in Canada declined
from 38 percent to 21 percent, while the unaffiliated population tripled from 7
percent to 23 percent. This paper examines the role of demographic factors such
as increased group size in decreased religious intermarriage among the
unaffiliated. Using census and survey data, we estimate probit models of
religious intermarriage for unaffiliated men and women. The models include
individual and group-level characteristics. Results show that for both sexes,
relative group size was the single largest contributor to decreased
intermarriage. Increased group size allowed the expression of endogamous or
within-group marital preferences among the unaffiliated. This secular endogamy,
or preference for within-group marriage among the unaffiliated, represents an
increasingly important form of religion-related marriage as the unaffiliated
population grows.
PMID- 29961487
TI - Using latent class analysis to produce a typology of environmental concern in the
UK.
AB - Factor analysis is often used to study environmental concern. This choice of
methodology is driven by predominant theories that tie environmental attitudes to
the multidimensional construct of environmental concern. This paper demonstrates
that using a clustering method such as latent class analysis can be a valuable
tool for studying environmental attitudes as they exist within a given
population. In making the case for the value of latent class analysis in this
context, we examine UK public concern for the environment and how this concern is
associated with pro-environmental behaviours. To do this we use responses to
DEFRA's 2009 Survey of Public Attitudes and Behaviours towards the Environment,
which is still the most nationally representative survey of its type in the UK.
Grouping respondents according to homogenous response patterns, we identify four
classes of people, defined by their concern for the environment: Pro-environment,
Neutral Majority, Disengaged and Paradoxical. To understand how these attitude
classes are associated with behaviour and socio-economic status, class membership
probability is regressed onto education, income and social grade, as well as 16
measures of environmental behaviour related to transport, food, recycling and
home energy conservation. The results contradict most previous research with the
environmental attitude classes by being highly predictive of environmental
behaviour.
PMID- 29961488
TI - Gender differences in the impact of job mobility on earnings: The role of
occupational segregation.
AB - In recent years, researchers have begun to explore the extent to which the impact
of switching firms (inter-firm mobility) on wages varies between men and women.
Using data from the NLSY79 from 1979 to 2012, this paper extends existing
research by exploring how occupational segregation and individual level factors
contribute to gender differences in the impact of voluntary inter-firm mobility
on wages. The paper also examines how patterns vary depending on education level.
Findings suggest that men without a college education receive greater wage gains
from voluntary inter-firm mobility than similarly educated women although there
is no overall gender difference for individuals with a bachelor's degree. The
wage returns to voluntary inter-firm mobility for both men and women increase as
a function of the male representation in the occupation. For individuals without
a college education, the male premium to voluntary inter-firm mobility is largest
in highly male dominated occupations. However, women with a bachelor's degree
employed in highly male dominated occupations use voluntary inter-firm mobility
to narrow the gender wage gap.
PMID- 29961489
TI - Occupational status benefits of studying abroad and the role of occupational
specificity - A propensity score matching approach.
AB - Occupational status benefits of student mobility remain uncertain, despite
increasing interest in the implications of international student mobility for the
reproduction of societal inequality. Since mobile young people are a selective
group in terms of socio-economic and achievement-oriented factors, we apply
propensity score techniques to test whether German higher education graduates who
did or did not study abroad differ in occupational status (based on the Socio
Economic Index of Occupational Status) three years after graduation. Analyses are
based on multi-cohort representative data of the German population (Working and
Learning in a Changing World). Results confirm a positively biased effect of
mobility on early career occupational status driven by compositional differences.
Subgroup analyses show that even when accounting for this bias, occupational
status returns to mobility are positive for those graduating in occupationally
unspecific fields of study. There are no returns for those graduating in
occupationally specific fields of study. Findings also suggest that the effect of
studying abroad is not homogeneous across the study population. Individuals less
likely to study abroad are at the same time more likely to reap the occupational
benefits from this experience.
PMID- 29961490
TI - Diversity preferences among employees and ethnoracial workplace segregation.
AB - Ethno-racial workplace segregation increases already existing ethno-racial
inequality. While previous research has identified discriminatory employers as
drivers of workplace segregation, this study addresses the role of the employees.
Sociological and social psychological theory suggest that people prefer to
surround themselves with people who positively confirm their social identity or
who contribute with higher group status. Through web-based surveys, we measure
employee attitudes and preferences concerning ethno-racial workplace diversity,
to what extent they differ by ethnicity/race, and if they contain intersectional
patterns. Thereafter, we use simulation models to analyze the consequences for
workplace segregation that these preferences would have, if realized. The main
survey results showed that all ethno-racial groups favored their own in-group as
colleagues, especially European Americans. As a secondary choice, the respondents
preferred the out-group with the highest labor market status. Intersectional
patterns were identified, as minority women were preferred as colleagues over
minority men. Our simulation model, based on the results of two surveys on stated
vs. indirectly revealed preferences, showed that employee preferences were at
best not diverse enough to desegregate workplaces. When based on the most common
preferences (i.e. excluding a few outliers), the simulations even suggested that
these preferences can cause segregation. We relate these findings to Schelling's
model of segregation.
PMID- 29961491
TI - Less equal, less trusting? Longitudinal and cross-sectional effects of income
inequality on trust in U.S. States, 1973-2012.
AB - Does income inequality reduce social trust? Although both popular and scholarly
accounts have argued that income inequality reduces trust, some recent research
has been more skeptical, noting these claims are more robust cross-sectionally
than longitudinally. Furthermore, although multiple mechanisms have been proposed
for why inequality could affect trust, these have rarely been tested explicitly.
I examine the effect of state-level income inequality on trust using the 1973
2012 General Social Surveys. I find little evidence that states that have been
more unequal over time have less trusting people. There is some evidence that the
growth in income inequality is linked with a decrease in trust, but these effects
are sensitive to how time is accounted for. While much previous inequality and
trust research has focused on status anxiety, this mechanism receives the little
support, but mechanisms based on social fractionalization and on exploitation and
resentment receive some support. This analysis improves on previous estimates of
the effect of state-level inequality on trust by using far more available
observations, accounting for more potential individual and state level
confounders, and using higher-quality income inequality data based on annual IRS
tax returns. It also contributes to our understanding of the mechanism(s) through
which inequality may affect trust.
PMID- 29961492
TI - Varying weekly work hours and earnings instability in the Great Recession.
AB - Unstable work schedules are increasingly a prominent stratification outcome,
particularly for low-wage workers. Nationally representative and longitudinal
research on the topic is limited, however. This article examines varying numbers
of weekly work hours among hourly workers, their increase during the Great
Recession of the late 2000s, and their impact on growing earnings instability.
Using data from the Survey of Income and Program Participation (SIPP), the
cumulative probability of ever reporting varying hours among hourly workers
increased from 36 percent between 2004 and 2007 to 46 percent between 2008 and
2012. Changes in state-level economic conditions, particularly state-level
unemployment rates and economic growth, largely explain the increase in varying
hours, consistent with arguments that employers pass the costs of volatile demand
onto workers. Finally, variance function regressions show the growth of varying
hours accounts for the significant increase in earnings instability from 2004-7
to 2008-12.
PMID- 29961493
TI - Introduction to the Issue.
PMID- 29961494
TI - The First Case of Riboflavin Transporter Deficiency in sub-Saharan Africa.
AB - This report describes the first case of a child with genetically confirmed Brown
Vialetto-van Laere syndrome in sub-Saharan Africa. This is an extremely rare
clinical condition that presents with an auditory neuropathy, bulbar palsy,
stridor, muscle weakness, and respiratory compromise that manifests with
diaphragmatic and vocal cord paralysis. It is an autosomal recessive condition
for which the genetic mutation has only recently been linked to a riboflavin
transporter deficiency. We describe an 11-month-old affected male infant. He has
required long-term respiratory support and a gastrostomy tube to support feeding.
With high-dose riboflavin supplementation, he had limited recovery of motor
function. His respiratory chain enzyme studies were abnormal suggestive of
mitochondrial (mt) dysfunction. In the setting of limited resources, recognition
of this striking clinical phenotype is important to highlight, specifically
regarding the genetic implications of the condition and the potentially remedial
response to vitamin supplementation.
PMID- 29961495
TI - A 15-Year-Old Boy With Refractory Status Epilepticus.
AB - In this case report, we discuss a 15-year-old previously healthy boy who
presented with acute onset encephalopathy with refractory status epilepticus
requiring pentobarbital-induced burst suppression for seizure control. We review
the differential diagnosis and important diagnostic considerations for pediatric
patients presenting with acute encephalopathy. We then review Hashimoto
encephalopathy (SREAT) and discuss presentation, diagnosis, and treatment.
PMID- 29961496
TI - A Newborn With Hyperlactatemia and Epileptic Encephalopathy.
AB - The etiology of hyperlactatemia in newborns could be a challenging diagnosis. In
this article we are discussing a diagnostic paradigm using the clinical history,
laboratory results, and brain imaging that could be helpful in directing the work
up.
PMID- 29961497
TI - Status Epilepticus-The Hunt for Treatable Causes.
PMID- 29961498
TI - "Cerebral Palsy" in a Patient With Arginase Deficiency.
AB - Inborn errors of metabolism (IEMs) are thought to present in infancy with acute
decompensation including feeding intolerance and vomiting, lethargy, and coma.
Most practitioners assume that children will be diagnosed in their first months
of life. However, certain IEMs present more insidiously, and occasionally
children fail to receive newborn screening resulting in delayed diagnoses, as
metabolic and genetic disorders are overlooked causes of cognitive and neurologic
deficits. Although signs and symptoms may be present but subtle, careful and
detailed history taking, particularly of a child's diet and neurologic medical
history, in addition to certain physical examination findings may suggest a
diagnosis that is later supported by laboratory and radiographic testing. We
present the case of an 11-year-old girl who presented with a diagnosis of
cerebral palsy, seizure disorder, and concerns of fatigue and increasing seizure
frequency. During hospitalization, she was found to have hyperammonemia, and a
diagnosis of arginase deficiency was made. More thorough review of her previous
records may have raised suspicion for IEM earlier.
PMID- 29961499
TI - Hypothalamic Hamartoma With Infantile Spasms: Case Report With Surgical
Treatment.
AB - We report a 10-month-old boy with treatment-resistant infantile spasms associated
with hypothalamic hamartoma (HH). Electroencephalography before surgical
treatment showed modified hypsarrhythmia. Transventricular endoscopic resection
and disconnection resulted in immediate and enduring disappearance of the
epileptic spasms and improvement in the postoperative electroencephalography.
After 8 years of treatment, the patient has nondisabling gelastic seizures
associated with a small amount of residual HH but no other seizure types. He is
not taking any antiepilepsy drugs. He is academically and socially successful. We
are not aware of any prior reports of surgical treatment of HH with concurrent
infantile spasms as an uncontrolled seizure type. The immediate disappearance of
infantile spasms demonstrates that the HH lesion itself is an active and
necessary component within the epileptic network responsible for spasms in this
particular condition. This case contributes to the recognition that focal
pathologies can be responsible for infantile spasms with hypsarrhythmia and
respond successfully to surgical intervention.
PMID- 29961500
TI - Editorial Comment: Case #26 Hypothalamic Hamartoma and Infantile Spasms.
PMID- 29961501
TI - A 2-Year-Old Boy With Difficulty Waking After Bone Marrow Transplantation.
AB - We report a 2-year-old boy who was evaluated for difficult waking during
prolonged intensive care unit admission associated with bone marrow transplant
for Wiskott-Aldrich syndrome. Neurologic examination was found to be abnormal,
with nuchal rigidity initially, then decreased extremity movement and areflexia
developing over several days. Electromyogram showed length-dependent, axonal,
sensorimotor polyneuropathy. Cerebrospinal fluid showed albuminocytologic
dissociation suggestive of Guillain-Barre syndrome or acute motor and sensory
axonal neuropathy variant. The patient was treated with immunotherapy and slowly
showed signs of motor recovery over several months. A review of Wiskott-Aldrich
syndrome, Guillain-Barre syndrome, immune-mediated complications of bone marrow
transplantation, and acute weakness in the intensive care unit is provided in
this case report.
PMID- 29961502
TI - A 15-Year-Old Girl With Sudden Onsent Reversible Neurologic Symptoms After
Cranial Irradiation for Medulloblastoma.
AB - A 15-year-old girl with history of medulloblastoma was evaluated for headache and
neurologic deficits 5 years after completion of initial radiation therapy and 3
years following completion of reirradiation. Neurologic examination was notable
for new-onset left hemianopia, hemiparesis, and neglect. Magnetic resonance
imaging showed extensive areas of cortical T2 prolongation and thickening
involving the right parietal, occipital, and temporal lobes with associated
extensive gyral enhancement. Upon spontaneous resolution of her weakness after 4
days, repeat magnetic resonance imaging showed resolution of the edema and gyral
enhancement, suggestive of the diagnosis of stroke-like migraine attacks after
radiation therapy (SMART syndrome). A review of SMART is provided in this case
report.
PMID- 29961503
TI - A 15-Month-Old Girl Presenting With Clitoromegaly and a Chest Mass.
AB - A 15-month-old girl was initially referred for endocrine evaluation for
clitoromegaly and subsequently found to have an adrenal mass that tracked along
the paravertebral region and was associated with increased vascular markings
along the skin. Neurologic examination was normal. Magnetic resonance imaging of
the chest mass demonstrated a serpiginous lesion along the intercostal margins.
Initial differential diagnosis included neuroblastoma, ganglioneuroblastoma,
vascular lesion, or nerve sheath tumor. Biopsy was consistent with plexiform
neurofibroma. Subsequent examination revealed features consistent with
neurofibromatosis type 1. A review of clinical features of NF1 is provided in the
case report.
PMID- 29961504
TI - Multifocal Brain Lesions With Extensive Perilesional Edema in a Young Boy
Returning From Kenya.
AB - We report the case of an 8-year-old boy who presented with headaches, optic disc
edema, and left eye esotropia. He had recently returned to the United States
after living in Kenya for approximately 3 years. His brain magnetic resonance
imaging showed multifocal lesions with significant perilesional edema seemingly
out of proportion to his neurologic examination findings. With appropriate
therapy there was remarkable improvement in his symptoms with reduction in size
of the lesions and surrounding edema.
PMID- 29961505
TI - Intracranial Calcifications in Young Children.
AB - Intracranial calcifications in young infants, while suggesting intrauterine
infections, can also be due to numerous other conditions, including rare genetic
disorders. We describe 2 children in whom the presence and pattern of
intracranial calcifications led to the diagnosis of uncommon genetic disorders,
Adams-Oliver syndrome and Aicardi-Goutieres syndrome. Differentiating genetic
conditions from intrauterine infections or other causes of intracranial
calcifications enables practitioners to provide accurate counseling regarding
prognosis and recurrence risk.
PMID- 29961506
TI - Editorial Comment: Cases #27-31.
PMID- 29961507
TI - Editorial Comment: Brown-Vialetto-Van Laere and the Advances in Molecular
Medicine.
PMID- 29961508
TI - Novel Homozygous Variant in TTC19 Causing Mitochondrial Complex III Deficiency
with Recurrent Stroke-Like Episodes: Expanding the Phenotype.
AB - A 7-year-old boy with family history of consanguinity presented with
developmental delay and recurrent hemiplegia involving both sides of the body,
with variable facial and ocular involvement. Brain MRI showed bilateral striatal
necrosis with cystic degeneration and lactate peaks on spectroscopy. Biochemical
testing demonstrated mildly elevated lactate and pyruvate. Whole-exome sequencing
revealed a novel homozygous pathogenic frameshift mutation in gene TTC19,
diagnostic of mitochondrial complex III deficiency.
PMID- 29961509
TI - Genetic, Radiologic, and Clinical Variability in Brown-Vialetto-van Laere
Syndrome.
AB - Brown-Vialetto-van Laere syndrome is characterized by a progressive sensorimotor
neuropathy, optic atrophy, hearing loss, bulbar dysfunction, and respiratory
insufficiency. Mutations in SLC52A2 and SLC52A3, encoding riboflavin transporters
RFVT2 and RFVT3, respectively, are the genetic basis of this disorder, often
referred to as riboflavin transporter deficiency types 2 and 3, respectively. We
present cases of both types of riboflavin transporter deficiency, highlighting
the distinguishing clinical features of a rapidly progressive motor or
sensorimotor axonal neuropathy, optic atrophy, sensorineural hearing loss, and
bulbar dysfunction. One child presented with isolated central apnea and
hypoventilation, not previously described in genetically confirmed Brown-Vialetto
van Laere, later complicated by diaphragmatic paralysis secondary to phrenic
nerve palsy. Magnetic resonance imaging showed T2 hyperintensity in the dorsal
spinal cord in 2 children, as well as previously unreported cervical nerve root
enlargement and cauda equina ventral nerve root enhancement in 1 child. Novel
homozygous mutations were identified in each gene-a NM_024531.4(SLC52A2):c.505C >
T, NP_078807.1(SLC52A2):p.(Arg169Cys) variant in SLC52A2 and
NM_033409.3(SLC52A3):c.1316G > A, NP_212134.3(SLC52A3):p.(Gly439Asp) variant in
SLC52A3. Both treated children showed improvement on high-dose riboflavin
supplementation, highlighting the importance of early recognition of this
treatable clinical entity.
PMID- 29961510
TI - A Novel Phenotype in a Previously Described Epilepsy-Aphasia Disorder.
AB - The clinical presentation of patients with epileptic encephalopathies can be
heterogenous. When attempting to classify a patient's epilepsy syndrome,
challenges can arise due to the phenotypic overlap of various epilepsies as well
as the different presentations of mutations within the same gene. Genetic testing
can be most helpful in evaluation of children with features spanning several
epilepsy phenotypes. In this case, we report on a boy with an epileptic
encephalopathy found to have a previously unreported mutation in a recently
described gene.
PMID- 29961511
TI - Language Regression in an Atypical SLC6A1 Mutation.
AB - Recent technological advances in exome sequencing or targeted gene sequencing
with epilepsy panels have allowed clinicians to better understand the
pathogenesis and clinical presentation of children with epilepsy. We present a
child with a SLC6A1 mutation with language delay and autistic spectrum disorder
and remind the reader that the identification of specific mutations in these
conditions increase the likelihood of identification of potential therapeutic
targets.
PMID- 29961512
TI - Neonatal epileptic encephalopathy caused by de novo GNAO1 mutation misdiagnosed
as atypical Rett syndrome: Cautions in interpretation of genomic test results.
AB - Epileptic encephalopathies are childhood brain disorders characterized by a
variety of severe epilepsy syndromes that differ by the age of onset and seizure
type. Until recently, the cause of many epileptic encephalopathies was unknown.
Whole exome or whole genome sequencing has led to the identification of several
causal genes in individuals with epileptic encephalopathy, and the list of genes
has now expanded greatly. Genetic testing with epilepsy gene panels is now done
quite early in the evaluation of children with epilepsy, following brain imaging,
electroencephalogram, and metabolic profile. Early infantile epileptic
encephalopathy (EIEE1; OMIM #308350) is the earliest of these age-dependent
encephalopathies, manifesting as tonic spasms, myoclonic seizures, or partial
seizures, with severely abnormal electroencephalogram, often showing a
suppression-burst pattern. In this case study, we describe a 33-month-old female
child with severe, neonatal onset epileptic encephalopathy. An infantile epilepsy
gene panel test revealed 2 novel heterozygous variants in the MECP2 gene; a 70-bp
deletion resulting in a frameshift and truncation (p.Lys377ProfsX9) thought to be
pathogenic, and a 6-bp in-frame deletion (p.His371_372del), designated as a
variant of unknown significance. Based on this test result, the diagnosis of
atypical Rett syndrome (RTT) was made. Family-based targeted testing and
segregation analysis, however, raised questions about the pathogenicity of these
specific MECP2 variants. Whole exome sequencing was performed in this family
trio, leading to the discovery of a rare, de novo, missense mutation in GNAO1 (p.
Leu284Ser). De novo, heterozygous mutations in GNAO1 have been reported to cause
early infantile epileptic encephalopathy-17 (EIEE17; OMIM 615473). The child's
severe phenotype, the family history and segregation analysis of variants and
prior reports of GNAO1-linked disease allowed us to conclude that the GNAO1
mutation, and not the MECP2 variants, was the cause of this child's neurological
disease. With the increased use of genetic panels and whole exome sequencing, we
will be confronted with lists of gene variants suspected to be pathogenic or of
unknown significance. It is important to integrate clinical information, genetic
testing that includes family members and correlates this with the published
clinical and scientific literature, to help one arrive at the correct genetic
diagnosis.
PMID- 29961513
TI - Infantile Epileptic Encephalopathy With Multiple Genetic Mutations: How Important
are Variants of Undetermined Significance?
AB - The importance of so called variants of undetermined significance in the
development of Infantile Epileptic Encephalopathy is discussed and an
illustrative case is presented.
PMID- 29961514
TI - The More Things Change... Child Neurology in the Age of Next-Generation
Sequencing.
PMID- 29961515
TI - The Terrible Summer of 1952 ... When Polio Struck Our Family.
AB - This is the story of my twin brother's struggle with polio. The story reflects
the thoughts and feelings of Lyle and members of his family and describes how we
all coped with the event.
PMID- 29961516
TI - Editorial: A Terrible Time.
PMID- 29961517
TI - Elevated Creatine Kinase in a 6-Year-Old Boy.
AB - Paucisymptomatic or asymptomatic but persistently elevated serum creatine kinase
is not an uncommon pediatric neurology referral question. The challenge is in
promptly identifying etiologies with specific treatments, even if they are rare.
The presenting features for a child or adolescent with juvenile-onset Pompe
disease (JOPD) can be nonspecific and heterogeneous. Clinical manifestations can
appear at any age after 2 years and before adulthood, with insidious onset of
symptoms related to slowly progressive skeletal or respiratory muscle weakness.
This reported case highlights the importance of screening for JOPD in children
with "hyper-CK-emia." Dried blood spot measuring acid alpha-glucosidase enzyme
activity is reliable, rapid, noninvasive, and inexpensive, allowing early
diagnosis. Diagnosis of JOPD is important as enzyme replacement therapy with
alglucosidase alpha, an intravenous recombinant alpha-glucosidase, is available,
and early treatment improves muscle function, quality of life, and long-term
survival.
PMID- 29961518
TI - McArdle Disease Presenting With Muscle Pain in a Teenage Girl: The Role of Whole
Exome Sequencing in Neurogenetic Disorders.
AB - We present the case of a young woman with worsening attacks of muscle pain and
rhabdomyolysis beginning at age 14. Initial metabolic testing and
electromyography revealed findings of a nonspecific myopathy. Diagnostic options
were discussed among the members of a neurogenetics clinic team. Whole-exome
sequencing was selected as a first tier test. This testing revealed a known
disease causing mutation in the PYGM gene consistent with McArdle disease. We
discuss the decision to use whole-exome sequencing in diagnostics and the
rationale for making this our choice as a first-level test modality.
PMID- 29961519
TI - Infantile-Onset Myelin Protein Zero-Related Demyelinating Neuropathy Presenting
as an Upper Extremity Monoplegia.
AB - We describe an infant with an early-onset demyelinating neuropathy who presented
with an upper extremity monoplegia and progressive asymmetric weakness.
Neurophysiologic testing revealed a generalized severe neuropathy with marked
slowing of nerve conduction. The disproportionate severity and asymmetry of upper
extremity involvement at presentation was atypical of inherited neuropathies, and
an initial diagnosis of chronic inflammatory demyelinating polyneuropathy was
considered. Nerve biopsy showed severe depletion of large myelinated fibers
without inflammatory cells, and focally folded myelin sheaths were seen on
electron microscopy. Genetic testing revealed a de novo heterozygous mutation in
the myelin protein zero gene.
PMID- 29961520
TI - The Curse of Apneic Spells.
AB - A 6-year-old girl had reduced fetal movements, numerous apneic spells, muscle
hypotonia, and developmental motor delay. Her muscle biopsy tissue showed
variation in myofiber diameters, small minicores by electron microscopy, and near
uniformity of type I fibers. Although no mutations were detected in RYR1, SEPN1,
and DMPK genes, the RAPSN gene revealed one known mutation, p.Asn88Lys, from the
mother, and one novel mutation, p.Cys366Gly, from the father. Life-saving
pyridostigmine treatment suppressed her apneic spells and improved her motor
development.
PMID- 29961521
TI - Editorial (To Follow Cases #9-12).
PMID- 29961522
TI - Consideration of Genetic Diagnoses of Developmental Delay in Children of
Consanguineous Families.
AB - In patients presenting with global developmental day, eliciting a history of
consanguinity may increase a clinician's bias toward suspecting an autosomal
recessive etiology. We present 3 cases wherein children of consanguineous parents
presented to the pediatric neurology clinic for evaluation and potential
diagnosis of the cause of global developmental delay. The outcome of the
investigations in each case demonstrate the need to follow established guidelines
for appropriate genetic testing as they pertain to the patient's presentation
rather than a single element of the history (ie, consanguinity).
PMID- 29961523
TI - Facial Weakness and Ophthalmoplegia in a 4-Day-Old Infant.
AB - We present a neonate with neurologic deficits recognized at 4 days of age. A male
infant was born at term via emergency cesarian section due to failure to progress
and fetal decelerations. He underwent therapeutic hypothermia for hypoxic
ischemic encephalopathy. Upon completion of rewarming, he was noted to have left
facial palsy, abduction deficit on the left eye past the midline, and nystagmus
involving the right eye. Brain magnetic resonance imaging showed a pontine
stroke, and computed tomography angiogram revealed basilar artery thrombosis. He
was treated with enoxaparin for 3 months, followed by low-dose aspirin. The
mechanism of the stroke remains unclear, and there is limited evidence to guide
management.
PMID- 29961524
TI - Editorial Comment Case #14 Basilar Artery Thrombosis in a Neonate.
PMID- 29961525
TI - Focal Epilepsy in a Teenager With Facial Atrophy and Hair Loss.
AB - There is increasing evidence to demonstrate that Parry-Romberg syndrome and
linear scleroderma en coup de sabre are both forms of linear scleroderma,
representing localized autoimmune conditions affecting the skin, eyes, brain, and
surrounding tissues. We present a case highlighting the clinical presentation of
a 12-year-old boy with focal seizures and physical examination findings of facial
atrophy and hair loss. This article reviews the literature related to the
presentation, epidemiology, diagnosis, and treatment of Parry-Romberg syndrome
and linear scleroderma en coupe de sabre with focus on the significant
correlation with neurologic disease, particularly seizures.
PMID- 29961526
TI - Pseudobulbar Affect in Survivors of Extreme Prematurity With Cerebellar Injury:
Support for the Cerebellar Link in Pathologic Laughter and Crying.
AB - Pseudobulbar affect, that is, pathologic laughter and crying is being
increasingly recognized in adults and is seen in association with a number of
diseases like Parkinson disease, dementia, traumatic encephalopathy, and others,
but has not previously been described in children with cerebral palsy. The
condition pseudobulbar affect may be due to lesions in (or degeneration of) the
cerebro-ponto-cerebellar pathways. Here we report 2 children with cerebral palsy
who have structural cerebellar injury because of their being born extremely
premature who have pathologic crying and probably laughter.
PMID- 29961527
TI - A Case of An Unusual Bell's Palsy Mimic.
AB - We discuss the case of a 5-year-old boy who presented with an isolated left-sided
cranial nerve 7 palsy that was initially magnetic resonance imaging negative.
Owing to continued symptoms, repeat magnetic resonance imaging was performed and
showed a temporal bone encephalocele. A review of the differential diagnosis of
cranial nerve 7 palsy, warning signs signaling the need for additional workup,
and a discussion of temporal lobe encephaloceles is provided in this case report.
It is important to recognize that structural lesions can closely mimic idiopathic
Bell's palsy, despite initial negative imaging.
PMID- 29961528
TI - A 20-Month-Old Girl With Fever, Seizures, Hemiparesis, and Brain Lesions
Requiring a Diagnostic Brain Biopsy.
AB - We report a case of a 20-month-old girl with atypical presentation of a fairly
common condition. She presented with acute onset of fever, seizures, and
hemiparesis. Her cerebrospinal fluid showed total nucleated cells 10/mm3 with
lymphocyte dominance. Polymerase chain reaction was negative for herpes simplex
virus. Computed tomography of head showed a cerebral hemorrhage of the left
frontal lobe and small subarachnoid hemorrhage in the right frontal region. Brain
magnetic resonance imaging revealed multiple foci of hyperintensity in bilateral
parietal lobes and right basal ganglia. She remained clinically stable without a
specific therapy. Her diagnosis was made after a brain biopsy.
PMID- 29961529
TI - Diplopia With Dural Fibrotic Thickening.
AB - Idiopathic hypertrophic pachymeningitis (HP) is a rare disorder of diffuse
thickening of the cranial or spinal dura mater without an identifiable cause.
Most common in adult males, idiopathic HP typically presents with headache with
or without varied associated focal neurologic deficits and findings of dural
enhancement on magnetic resonance imaging in a linear, nodular, or combined
pattern. As it is felt to be an autoimmune disorder, treatment with high-dose
corticosteroids is typically recommended, and without intervention, the course is
usually progressive. The disease can commonly progress with a relapsing remitting
course requiring other immune modulators such as methotrexate, azathioprine, or
cyclophosphamide for control. Here, we describe a unique case of idiopathic HP as
it presented in a pediatric patient and resolved without immunomodulatory
therapy.
PMID- 29961530
TI - A Quiet Disease With Loud Manifestations.
AB - Cytomegalovirus (CMV) is the most common congenital virus passed from mother to
fetus in the United States, and the most common acquired cause of sensorineural
hearing loss. Neuroimaging in patients with symptomatic congenital CMV
demonstrates abnormalities frequently, but many providers are unaware of the
extent of these findings. We present a case of a 15-month-old girl with
progressive sensorineural hearing loss and developmental delays. Magnetic
resonance imaging of her brain was done by her otolaryngologist as part of a
routine cochlear implant evaluation where it was found to be drastically abnormal
and reported as a likely leukodystrophy. It was subsequently found to be related
to congenital CMV on further evaluation. Congenital CMV should be considered in
the differential of white matter hyperintensities, especially in the setting of
sensorineural hearing loss, developmental delays, or both, and given how common
CMV is around the world.
PMID- 29961531
TI - A Boy With Red Ears.
AB - Vague complaints of ear pain can bring frustration in the neurology office as the
differential is broad and often nonneurologic. Herein, we present a case of red
ear syndrome, a treatable migraine variant that can cause significant distress
and lead to delayed treatment if not considered as a diagnostic possibility.
PMID- 29961532
TI - Editorial to Follow Case #21 Regarding Cases #14-21.
PMID- 29961533
TI - Atypical Presentation of a Progressive and Treatable Encephalopathy in an Older
Child With Gelastic and Dacrystic Seizures.
AB - We discuss an unusual case of a teenage boy who presented with waxing and waning
cognitive decline and gelastic-dacrystic seizures, evolving later into a rapidly
progressive encephalopathy with status epilepticus. Extensive genetic and
metabolic testing did not lead to a specific diagnosis. Cerebrospinal fluid
studies performed during admission to the intensive care unit provided the
information needed to establish a diagnosis. After implementation of specific
treatment, his seizures stopped and his background electroencephalogram returned
to normal. He has remained largely seizure-free experiencing a significant
cognitive recovery. This case illustrates the importance of performing
cerebrospinal fluid analysis in patient with refractory seizures and cognitive
decline of unknown etiology.
PMID- 29961534
TI - Do Patients Really Need to Be Prone for Foot or Ankle Surgery?
PMID- 29961535
TI - Seeing the Future: A Crystatistical Ball.
AB - We are used to identifying risk factors, or predisposing factors, for outcomes of
interest, whether those outcomes are negative or positive, using the tools of
statistical modeling. We are far less accustomed to making predictions of
outcomes for specific individuals or testing the accuracy of those predictions.
In this commentary, we consider this more difficult task and discuss, in this
context, why statistics has such difficulty talking about individuals, even as it
easily informs us about populations.
PMID- 29961536
TI - Erratum.
PMID- 29961537
TI - Erratum.
PMID- 29961538
TI - Inheritance of epigenetic dysregulation from male factor infertility has a direct
impact on reproductive potential.
AB - OBJECTIVE: To evaluate the epigenetic consequence on the methylome and subsequent
transcriptome in euploid blastocysts of male-factor (MF) infertility patients.
DESIGN: Methylome and transcriptome analysis on individual
oligoasthenoteratozoospermia (OAT [MF]) blastocysts. SETTING: Infertility clinic.
PATIENT(S): Clinical data from 128 couples presenting with OAT (MF) and 118
maternal age-matched control (no MF) subjects undergoing infertility treatment
from 2010 to 2014, along with 72 surplus cryopreserved blastocysts donated from
33 couples with their informed consents. INTERVENTION(S): None. MAIN OUTCOME
MEASURE(S): Methyl Maxi-Seq (Zymo Research) was used to determine genome-wide DNA
methylation, and small cell number RNA-Seq was used to examine the global
transcriptome. Validation experiments were performed with the use of
pyrosequencing or quantitative real-time polymerase chain reaction. Statistical
analysis used Student t test, analysis of variance in R, Fisher exact test, and
pairwise fixed reallocation randomization test where appropriate, with
significance at P<.05. RESULT(S): Clinical pregnancy rates were similar between
OAT (MF) patients and control (no MF) subjects after euploid embryo transfer.
However, the miscarriage rate for OAT (MF) patients was significantly higher
(14.7% vs. 2.2%; P<.05). Methylome and transcriptome analyses of individual
blastocysts revealed significant alterations in 1,111 CpG sites and 469
transcripts, respectively (P<.05). Pathway analysis elucidated genes involved in
"regulation of cellular metabolic process" as universally affected. Validation of
the genome-wide approaches was performed for SBF1 and SLC6A9 (P<.05).
CONCLUSION(S): Methylation and transcription aberrations in individual OAT (MF)
blastocysts illustrate an epigenetic consequence of MF infertility on
embryogenesis, significantly altering key developmental genes and affecting
embryonic competence. This epigenetic dysregulation provides an explanation for
the reduced reproductive potential in OAT (MF) patients despite euploid
blastocyst transfers.
PMID- 29961539
TI - The left cradling bias: An evolutionary facilitator of social cognition?
AB - A robust left side cradling bias (LCB) in humans is argued to reflect an
evolutionarily old left visual field bias and right hemisphere dominance for
processing social stimuli. A left visual field bias for face processing, invoked
via the LCB, is known to reflect a human population-level right cerebral
hemisphere specialization for processing social stimuli. We explored the
relationship between cradling side biases, hand dominance and socio-communicative
abilities. Four and five year old typically-developing children (N = 98)
participated in a battery of manual motor tasks interspersed by cradling trials
comprising a(n): infant human doll, infant primate doll, proto-face pillow and no
face pillow. Mean social and communication ability scores were obtained via a
survey completed by each child's key teacher. We found a population-level LCB for
holding an infant human doll that was not influenced by hand dominance, sex, age
or experience of having a younger sibling. Children demonstrating a LCB, did
however, obtain a significantly higher mean social ability score compared with
their right side cradling counterparts. Like the infant human doll, the proto
face pillow's schematic face symbol was sufficient to elicit a population-level
LCB. By contrast, the infant primate doll elicited a population-level right side
cradling bias, influenced by both hand dominance and sex. The findings suggest
that the LCB is present and visible early in development and is likely therefore,
to represent evolutionarily old domain-specific organization and function of the
right cerebral hemisphere. Additionally, results suggest that a LCB requires
minimal triggering but can be reversed in some situations, possibly in response
to species-type or levels of novelty or stress as perceived by the viewer.
Patterns of behavioral biases within the context of social stimuli and their
associations with cognitive ability are important for understanding how socio
communication abilities emerge in developing children.
PMID- 29961540
TI - White matter neuro-plasticity in mental arithmetic: Changes in hippocampal
connectivity following arithmetic drill training.
AB - Verbally-mediated arithmetic fact retrieval has been suggested to be subserved by
a left-lateralized network including angular gyrus and hippocampus. However, the
contribution of these areas to retrieval of arithmetic facts has been under
debate lately, challenging the prominent role of the angular gyrus in arithmetic
fact retrieval. In the present study, we evaluated changes in structural
connectivity of left hippocampus and left angular gyrus in 32 participants
following a short extensive drill training of complex multiplication. We observed
a significant increase of structural connectivity in fibers encompassing the left
hippocampus but not the left angular gyrus. As such, our findings substantiate
that the left hippocampus plays a central role in arithmetic fact retrieval.
While both structures, left angular gyrus and left hippocampus seem to be parts
of the network processing arithmetic facts, hippocampus actually seems to
subserve encoding and retrieval of arithmetic facts. In turn, the role of the
left angular gyrus might rather be to mediate the fact retrieval network as to
whether or not processes of fact retrieval are referred to.
PMID- 29961541
TI - The prototype concept in a full digital implant workflow.
AB - BACKGROUND: The aim of this case report is to describe the innovative concept of
a prototype use in a digital implant workflow. A prototype is required for
simultaneous evaluation of the accuracy of a dental impression and esthetic and
functional parameters before final framework realization. CASE DESCRIPTION: Three
digital impressions were obtained to create a master file, which contained
information on the 3-dimensional (3D) position of the implant, the gingival
architecture, and the esthetic and functional features of the provisional
restoration. A stereolithographic master model (SMM) featuring implant analogs
was 3D printed. Two prototypes were realized with the use of 2 different
modalities. The first resin prototype (A), which lacked implant connections, was
produced with the use of a certified digital workflow process. The titanium
connections were luted onto the SMM. The second resin prototype (B), considered
experimental, was a single piece with milled implant connections. Both prototypes
were tested in the patient by means of visual inspection, finger pressure
testing, screw resistance testing, and periapical radiography. In the case of
accurate fit of prototype A or B on the SMM and misfit in the patient, the
impression should be invalidated. For prototype B, in the case of proper fit in
the patient and misfit on the SMM (because of the occurrence of an error during
3D printing, incorrect analog position, or both), the impression should be
validated, but the model should be adapted. CONCLUSIONS AND PRACTICAL
IMPLICATIONS: The use of a prototype allows the clinician to simultaneously test
implant position and esthetic and functional parameters. However, a single
structure prototype could be preferable for the identification of impression
inaccuracy.
PMID- 29961542
TI - Pain assessment in individuals with dementia and communication problems in Spain.
A systematic review.
AB - BACKGROUND AND OBJECTIVE: Pain assessment in individuals with advanced dementia
and communication problems continue to be underdiagnosed and undertreated due to
the difficulty in performing this assessment. This review explores and
synthesises how pain in individuals with advanced dementia and communication
problems are being assessed in the context of Spanish healthcare. MATERIALS AND
METHODS: A systematic review of the literature was conducted following the PRISMA
criteria. We reviewed the databases of PubMed, Web of Science, Cinahl, Scopus,
Dialnet and Cuitatge up to December 2017. Four independent reviewers identified
studies that included instruments to assess pain in individuals with dementia and
communication problems in the Spanish healthcare context. We performed a
narrative synthesis of the included articles. RESULTS: After applying the
inclusion criteria, 10 studies were included. Of these, 4 were methodological
studies validating Spanish versions of scales (Abbey, Algoplus, Doloplus and
PAINAD-Sp), and 1 was on the development of the original EDAD scale. We also
identified 3 studies conducted in Spain that used a translation of the PAINAD, 1
study that used a Spanish translation of Doloplus2 and 1 publication that
included the use in Spain of a scale not validated for this patient profile (Pain
VAS). CONCLUSIONS: There are currently several instruments validated in Spanish
to assess pain in individuals with advanced dementia and communication problems
(Abbey, Algoplus, Doloplus y PAINAD-Sp). However, these instruments have still
not been widely used in research, and their psychometric properties could be
improved.
PMID- 29961543
TI - The King Is Dead: Clark Gable's Heart Attack.
AB - Clark Gable was born in a small Ohio mining town and never finished high school.
Stage struck as a young man, he did menial jobs while working his way up to movie
stardom-his most famous role was in "Gone with the Wind." He married 5 times.
During WWII, he enlisted in the Army Air Corps, flew a few combat missions as a
gunner and won the Distinguished Service Cross. Personally, he was intermittently
obese, a drinker, smoker, hypertensive and predictably in 1960, he suffered an
acute myocardial infarction. His clinical course was benign until the 10th
hospital day, when he died suddenly. No resuscitation was attempted. At the time
of his death, preventive cardiology, mouth-to-mouth ventilation, closed chest
cardiac massage, defibrillation and coronary care units were in their infancy.
The history of these and subsequent therapeutic practices are reviewed, but Gable
died a bit too early for their application.
PMID- 29961544
TI - A computational model of pedestrian road safety: The long way round is the safe
way home.
AB - We propose a novel linear model of pedestrian safety in urban areas with respect
to road traffic crashes that considers a single independent variable of
pedestrian path safety. This variable is estimated for a given urban area by
sampling pedestrian paths from the population of such paths in that area and in
turn estimating the mean safety of these paths. We argue that this independent
variable directly models the factors contributing to pedestrian safety. This
contrasts previous approaches, which, by considering multiple independent
variables describing the environment, traffic and pedestrians themselves,
indirectly model these factors. Using data about 15 UK cities, we demonstrate
that the proposed model accurately estimates numbers of pedestrian casualties.
PMID- 29961545
TI - Inspired by the past and looking to the future of the Stroop effect.
PMID- 29961546
TI - An analysis of Drug Survival, Effectiveness, and Safety in Moderate to Severe
Psoriasis Treated With Ustekinumab: An Observational Study of 69 Patients in
Routine Clinical Practice.
PMID- 29961547
TI - Photodynamic Therapy in the Treatment of Cutaneous Leishmaniasis.
PMID- 29961549
TI - Editorial.
PMID- 29961548
TI - Google search patterns monitoring the daily health impact of heatwaves in
England: How do the findings compare to established syndromic surveillance
systems from 2013 to 2017?
AB - One of the implications of climate change is a predicted increase in frequent and
severe heatwaves. The impact of heatwaves on the health of the population is
captured through real-time syndromic healthcare surveillance systems monitored
daily in England during the summer months. Internet search data could potentially
provide improved timeliness and help to assess the wider population health impact
of heat by capturing a population sub-group who are symptomatic but do not seek
healthcare. A retrospective observational study was carried out from June 2013 to
September 2017 in England to compare daily trends in validated syndromic
surveillance heat-related morbidity indicators against symptom-based heatwave
related Google search terms. The degree of correlation was determined with
Spearman correlation coefficients and lag assessment was carried out to determine
timeliness. Daily increases in frequency in Google search terms during heatwave
events correlated well with validated syndromic indicators. Correlation
coefficients between search term frequency and syndromic indicators from 2013 to
2017 were highest with the telehealth service NHS 111 (range of 0.684-0.900 by
search term). Lag analysis revealed a similar timeliness between the data
sources, suggesting Google data did not provide a delayed or earlier signal in
the context of England's syndromic surveillance systems. This work highlights the
potential benefits for countries which lack established public health
surveillance systems to monitor heat-related morbidity and the use of internet
search data to assess the wider population health impact of exposure to heat.
PMID- 29961550
TI - Paired Analysis of Outcomes After Kidney Transplantation in Peritoneal and
Hemodialysis Patients.
AB - BACKGROUND: The impact of dialysis modality before kidney transplantation
(hemodialysis or peritoneal dialysis) on outcomes is not clear. In this study we
retrospectively analyzed the impact of dialysis modality on posttransplant follow
up. METHODS: To minimize donor bias, a paired kidney analysis was applied. One
hundred thirty-three pairs of peritoneal dialysis (PD) and hemodialysis (HD)
patients were transplanted at our center between 1994 and 2016. Those who
received kidneys from the same donor were included in the study. HD patients were
significantly older (44 vs 48 years), but the Charlson Comorbidity Index was
similar (3.12 vs 3.46) in both groups. The groups did not differ significantly
with respect to immunosuppressive protocols and number of mismatches (2.96 vs
2.95). RESULTS: One-year patient (98% vs 96%) and graft (90% vs 93%) survival was
similar in the PD and HD patient groups. The Kaplan-Meier curves of the patients
and graft survival did not differ significantly. Delayed graft function (DGF) and
acute rejection (AR) occurred significantly more often in the HD recipients.
Graft vessel thrombosis resulting in graft loss occurred in 9 PD (6.7%) and 4 HD
(3%) patients (P > .05). Serum creatinine concentration and estimated glomerular
filtration rate (using the Modification of Diet in Renal Disease guidelines)
showed no difference at 1 month, 1 year, and at final visit. On multivariate
analysis, factors significantly associated with graft loss were graft vessel
thrombosis, DGF, and graft function 1 month after transplantation. On univariate
analysis, age, coronary heart disease, and graft loss were associated with death.
Among these factors, only coronary heart disease (model 1) and graft loss were
significant predictors of death on multivariate analysis. CONCLUSION: The long
term outcome for renal transplantation is similar in patients with PD and HD.
These groups differ in some aspects, however, such as susceptibility to vascular
thrombosis in PD patients, and to DGF and AR in HD patients.
PMID- 29961551
TI - Outcomes of Prolonged Treatment With Intravenous Immunoglobulin Infusions for
Acute Antibody-mediated Rejection in Kidney Transplant Recipients.
AB - BACKGROUND: Treatment of antibody-mediated rejection (AMR) is one of the main
problems after kidney transplantation (KTx). The results of intensive AMR
treatment with plasmapheresis (PF) and repeated infusions of intravenous
immunoglobulin (IVIg) are presented. METHODS: Diagnosis of AMR was based on graft
biopsy and the presence of donor-specific antibodies (DSAs). AMR therapy
consisted of 5 PF and IVIg infusions given after the last PF. Subsequent IVIg
doses were given every 4 weeks for 6 months. Graft biopsy and DSA assessment were
repeated at the end of the treatment (ET). RESULTS: Four women and 10 men were
included in our study; mean time from KTx to AMR was 79 (range, 3-193) months.
During the treatment, 4 patients had graft failure. Graft function at baseline
was significantly worse (P = .02) in this group compared with patients who
completed the therapy. At baseline, mean flourescence intensity (MFI) was 6574
(range, 852-15,917) in the whole group, 7088 (range, 1054-15,917) in patients who
completed treatment, and 4828 (range, 852-11,797) in patients who restarted
hemodialysis. At ET, DSA MFI decreased in 8 of 10 patients (80%) who completed
the therapy. The MFI decrease was 3946 (range, 959-11,203). Control graft
biopsies revealed decreased intensity of C4d deposits in peritubular capillaries
in 7 patients (78%) and decreased peritubular capillaritis in 2 patients (22%).
CONCLUSION: Intensive, prolonged AMR therapy with PF and IVIg resulted in a
decrease in DSA titer and intensity of C4d deposits, but was not associated with
reduction of microcirculation inflammation. Treatment was ineffective in patients
with baseline advanced graft insufficiency.
PMID- 29961552
TI - Long-Term Shape, Curvature, and Depth Changes of the Lamina Cribrosa after
Trabeculectomy.
AB - PURPOSE: To evaluate changes in lamina cribrosa (LC) shape, curvature, and depth
after trabeculectomy. DESIGN: Prospective, observational case series.
PARTICIPANTS: A total of 112 patients (118 eyes) with open- or closed-angle
glaucoma undergoing trabeculectomy. METHODS: The optic nerve head was imaged
using enhanced depth imaging spectral-domain OCT before trabeculectomy and at 6
follow-up visits throughout the first postoperative year. The anterior LC surface
and Bruch's membrane opening were marked in the serial horizontal B scans for the
analysis of LC parameters using Morphology 1.0 software. Postoperative
morphologic LC changes were assessed. MAIN OUTCOME MEASURES: The postoperative LC
global shape index (GSI), nasal-temporal (N-T) and superior-inferior (S-I)
curvatures, and mean and sectoral LC depth (LCD). RESULTS: The mean LC GSI
increased only during the early postoperative period (P = 0.02), resulting in a
change toward the saddle-rut shape. There was a flattening of the LC curvature in
N-T (P < 0.001) and S-I (P = 0.003) meridians 12 months after trabeculectomy. A
shallowing of the mean and sectoral LCD from baseline was significant throughout
the entire follow-up period (P < 0.001) and progressed up to postoperative month
6. Twenty-eight patients showed a deepening of the LC from baseline in at least 1
visit. Eyes with shallower LCD compared with baseline responded to intraocular
pressure (IOP) reduction with greater movement anteriorly than eyes with deeper
LCD (P = 0.002). Greater IOP reduction (P = 0.007), less retinal nerve fiber
layer thinning over the year (P = 0.003), and more superiorly-inferiorly curved
baseline LC (P = 0.001) were associated with an increase in GSI. Younger age and
IOP reduction were related to LC shallowing (P < 0.001, P = 0.002) and N-T
flattening (P < 0.001). CONCLUSIONS: In most eyes, trabeculectomy resulted in
long-term flattening and shallowing of the LC. However, in some eyes, LC deepened
from baseline. Change in LC global shape appeared to be temporal. Reduction in
IOP plays an important role in the early phase of LC change; however, in the
later phase, LC remodeling may play a crucial role in view of stable IOP.
PMID- 29961553
TI - A case study for applying therapeutic jurisprudence to policymaking: Assembling a
policy toolbox to achieve a trauma-informed early care and learning system.
PMID- 29961555
TI - Author Reply.
PMID- 29961554
TI - Editorial Comment.
PMID- 29961556
TI - Association between attention-deficit/hyperactivity disorder (ADHD) and
amyotrophic lateral sclerosis (ALS).
PMID- 29961557
TI - Economic burden of resected (stage IB-IIIA) non-small cell lung cancer in France,
Germany and the United Kingdom: A retrospective observational study (LuCaBIS).
AB - OBJECTIVES: New adjuvant treatments are being developed for patients with
resected non-small cell lung cancer (NSCLC). Due to scarcity of real-world data
available for treatment costs and resource utilization, health technology and
cost-effectiveness assessments can be limited. We estimated the burden and cost
of-illness associated with completely resected stage IB-IIIA NSCLC in France,
Germany and the United Kingdom (UK). MATERIALS AND METHODS: Eligible patients
were aged >=18 years with completely resected stage IB-IIIA NSCLC between August
2009 and July 2012. Patients (living or deceased) were enrolled at clinical sites
by a systematic sampling method. Data were obtained from medical records and
patient surveys. Direct, indirect and patient out-of-pocket expenses were
estimated by multiplying resource use by country-specific unit costs. National
annual costs were estimated based on disease prevalence data available from
published sources. RESULTS: 39 centers provided data from 831 patients of whom
patient surveys were evaluable in 306 patients. Median follow-up was 26 months.
The mean total direct costs per patient during follow-up were: ?19,057 (France),
?14,185 (Germany), and ?8377 (UK). The largest cost drivers were associated with
therapies received (?12,375 France; ?3694 UK), and hospitalization/emergency
costs (?7706 Germany). Monthly direct costs per patient were the highest during
the distant metastasis/terminal illness phase in France (?15,562) and Germany
(?6047) and during the adjuvant treatment period in the UK (?2790). Estimated
mean total indirect costs per patient were: ?696 (France), ?2476 (Germany), and
?1414 (UK). Estimates for the annual national direct cost were ?478.4 million
(France), ?574.6 million (Germany) and ?325.8 million (UK). CONCLUSION: To our
knowledge, this is the first comprehensive study describing the burden of illness
for patients with completely resected stage IB-IIIA NSCLC. The economic burden
was substantial in all three countries. Treatment of NSCLC is associated with
large annual national costs, mainly incurred during disease progression.
PMID- 29961558
TI - Lessons for achieving health equity comparing Aotearoa/New Zealand and the United
States.
AB - Aotearoa/New Zealand (Aotearoa/NZ) and the United States (U.S.) suffer inequities
in health outcomes by race/ethnicity and socioeconomic status. This paper
compares both countries' approaches to health equity to inform policy efforts. We
developed a conceptual model that highlights how government and private policies
influence health equity by impacting the healthcare system (access to care,
structure and quality of care, payment of care), and integration of healthcare
system with social services. These policies are shaped by each country's culture,
history, and values. Aotearoa/NZ and U.S. share strong aspirational goals for
health equity in their national health strategy documents. Unfortunately,
implemented policies are frequently not explicit in how they address health
inequities, and often do not align with evidence-based approaches known to
improve equity. To authentically commit to achieving health equity, nations
should: 1) Explicitly design quality of care and payment policies to achieve
equity, holding the healthcare system accountable through public monitoring and
evaluation, and supporting with adequate resources; 2) Address all determinants
of health for individuals and communities with coordinated approaches, integrated
funding streams, and shared accountability metrics across health and social
sectors; 3) Share power authentically with racial/ethnic minorities and promote
indigenous peoples' self-determination; 4) Have free, frank, and fearless
discussions about impacts of structural racism, colonialism, and white privilege,
ensuring that policies and programs explicitly address root causes.
PMID- 29961560
TI - Training the global midwifery workforce.
PMID- 29961559
TI - Neoadjuvant chemotherapy in elderly women with ovarian cancer: Rates of use and
effectiveness.
AB - BACKGROUND: Neoadjuvant chemotherapy (NACT) may reduce perioperative morbidity in
women undergoing primary treatment for ovarian cancer. We evaluated patterns of
use and outcomes in a population-based cohort of elderly women with ovarian
cancer (OC). METHODS: A cohort of patients >=66 years old diagnosed between 2000
and 2013 with stage III-IV epithelial OC who received surgery and platinum/taxane
chemotherapy for primary treatment was identified from the SEER-Medicare
database. Propensity-score matching methods were used to examine differences in
outcomes. Kaplan-Meier analysis was performed to compare overall survival (OS) in
the matched cohort. RESULTS: From 2000 to 2013, 22.5% of older women received
NACT. The use of NACT increased over time from 16% in 2000 to 35.4% in 2013 (p <
.0001). Among women who received PCS, the rate of ostomy creation was higher
compared with NACT (23.3% vs. 10.8%, p < .0001). Infectious and other surgical
complications were higher among those who had PCS, regardless of stage. Median OS
of women III ovarian cancer who underwent PCS was longer compared with NACT (38.8
vs. 28 months, p <= .0001). There were no survival differences between NACT and
PCS in women with stage IV disease (29.4 vs. 29.8 months, p = .61) or for women
aged >80. CONCLUSION: Careful consideration should be given to older patients
prior to undergoing PCS. Survival outcomes were similar for patients with stage
IV disease, although NACT was associated with decreased perioperative morbidity
compared with PCS. Among women with stage III disease, PCS was associated with
improved overall survival, but higher rates of perioperative morbidity and acute
care.
PMID- 29961561
TI - Culture, bathing and hydrotherapy in labor: An exploratory descriptive pilot
study.
AB - OBJECTIVE: Though bathing (hydrotherapy) is widely used during labor to decrease
anxiety and pain and to promote relaxation, the influence of cultural beliefs
about bathing by parturients is virtually unknown. This pilot study explored
pregnant women's experiences of bathing, bathing in labor, and cultural beliefs
about bathing. DESIGN: An exploratory, descriptive design. SETTING: Low risk
obstetrical clinics. PARTICIPANTS: Healthy Hispanic, Black, White, American
Indian and Asian women (N = 41) at >37 weeks gestation. METHODS: During a routine
prenatal visit women responded to a brief openended questionnaire on the use of
bathing. Data was captured using a modified ethnographic method involving
observation and note taking with thematic analysis and quantification of percent
response rates. FINDINGS: Forty-six percent (N = 41) of women used bathing for
purposes other than hygiene but only 4.9% (N = 41) of these women bathed during a
previous labor. The women described bathing as relaxing, easing, calming, and
efficacious for relief of menstrual cramps and labor contractions. Ten percent of
women reported cultural beliefs about bathing. CONCLUSIONS: Women who bathe,
report relief of anxiety, menstrual and labor pain and promotion of mental and
physical relaxation. The findings do not support the view that bathing is
associated with identifiable cultural beliefs; rather, they suggest that bathing
is a self-care measure used by women. This practice is likely transmitted from
generation to generation by female elders through the oral tradition. Assumptions
that race or ethnicity precludes the use of bathing may be faulty. Cautionary
instructions should be given to pregnant women who are <37 completed weeks of
gestation, to avoid bathing for relief of cramping or contractions and to seek
immediate health care evaluation. Study of culturally intact groups may uncover
additional themes related to bathing in labor and as a self-care measure for
dysmenorrhea.
PMID- 29961562
TI - Usefulness of Oral Ferric Citrate in Patients With Iron-Deficiency Anemia and
Chronic Kidney Disease With or Without Heart Failure.
AB - Patients with chronic inflammatory conditions including chronic kidney disease
(CKD) and heart failure (HF) are undertreated with iron-deficiency anemia (IDA).
Progressive inflammation and reduced iron transport associated with CKD and HF
may reduce the efficacy of oral iron therapy. Oral ferric citrate improves anemia
markers in CKD, but its effects in patients with CKD and concomitant HF have not
been described. Patients with CKD not on dialysis and IDA from a phase 2 and 3
trial were treated with ferric citrate (n = 190) or placebo (n = 188); patients
with HF were identified from medical histories. Hemoglobin response was defined
as a >=10.0-g/L increase in hemoglobin. Changes in hemoglobin, transferrin
saturation, ferritin, and serum phosphate from baseline to week 12 and the
incidence of adverse events potentially related to HF were evaluated. HF was
reported in 22% (n = 81) of patients. The proportion of patients with hemoglobin
response to ferric citrate treatment did not significantly differ in patients
with and without HF (43% vs 49%, respectively; p = 0.47); changes from baseline
in hemoglobin, iron parameters, and serum phosphate were similar. Adverse events
potentially related to HF were noted more frequently in patients with HF (ferric
citrate, 23%; placebo, 17%) versus those without HF (ferric citrate, 12%;
placebo, 11%). In conclusion, these results indicate a potential role for ferric
citrate in the treatment of IDA in patients with CKD not on dialysis and
concomitant HF.
PMID- 29961563
TI - Influence of Sociodemographic Factors and Provider Specialty on Anticoagulation
Prescription Fill Patterns and Outcomes in Atrial Fibrillation.
AB - Early cardiology involvement after atrial fibrillation (AF) diagnosis is
associated with increased oral anticoagulant prescription fills and reduced
stroke risk. It is unknown if this association varies by race, sex, or education.
We examined anticoagulant fills in 223,891 patients with incident nonvalvular AF
(mean age = 71 years; 44% women; 84% white; 9% black; 5% Hispanic; 2% Asian) from
the Optum Clinformatics database (2009 to 2014). Provider specialty and filled
anticoagulant prescriptions 3 months before and 6 months after AF diagnosis were
obtained. Poisson regression was used to compute the probability of oral
anticoagulant prescription fill and Cox regression was used to estimate the risk
of stroke and major bleeding. Cardiology involvement was less likely among
nonwhites (white = Referent; black = relative risk = 0.96, 95% confidence
interval (0.95 to 0.97); Hispanic = 0.99 (0.98 to 1.00); Asian = 0.95 (0.93 to
0.97)) and women (0.92 (0.91 to 0.93)), but more likely with higher education
level (high school or less = Referent; some college = 1.03 (1.02 to 1.04);
college or more = 1.08 (1.07 to 1.09)). Patients seen by cardiology providers
were more likely to fill anticoagulant prescriptions (Any = 1.67 (1.64 to 1.69);
direct oral anticoagulants = 2.59 (2.49 to 2.68); warfarin = 1.38 (1.35 to 1.41))
compared with patients not seen by a cardiology provider. Patients seen by a
cardiologist had a reduced stroke risk (hazard ratio = 0.84 (0.79 to 0.88)) and
similar bleeding risk (1.01 (0.96 to 1.06)). Outcomes did not vary by race, sex,
or education level. In conclusion, although race, sex, and education differences
exist in early cardiology involvement after AF diagnosis, the influence of
cardiology involvement on anticoagulant prescription fills and AF-related
outcomes does not vary by these factors. Initiatives to improve early cardiology
referral in nonwhites, women, and those with lower educational attainment may
improve AF outcomes.
PMID- 29961564
TI - Microstructural Changes in Higher-Order Nuclei of the Thalamus in Patients With
First-Episode Psychosis.
AB - BACKGROUND: Disruption in the thalamus, such as volume, shape, and cortical
connectivity, is regarded as an important pathophysiological mechanism in
schizophrenia. However, there is little evidence of nuclei-specific structural
alterations in the thalamus during early-stage psychosis, mainly because of the
methodological limitations of conventional structural imaging in identifying the
thalamic nuclei. METHODS: A total of 37 patients with first-episode psychosis and
36 matched healthy control subjects underwent diffusion tensor imaging, diffusion
kurtosis imaging, and T1-weighted magnetic resonance imaging. Connectivity-based
segmentation of the thalamus was performed using diffusion tensor imaging, and
averages of the diffusion kurtosis values, which represent microstructural
complexity, were estimated using diffusion kurtosis imaging and were compared in
each thalamic nucleus between the groups. RESULTS: The mean kurtosis values in
the thalamic regions with strong connections to the orbitofrontal cortex (F1,70 =
8.40, p < .01) and the lateral temporal cortex (F1,70 = 8.46, p < .01) were
significantly reduced in patients with first-episode psychosis compared with
those of the healthy control subjects. The mean kurtosis values in the thalamic
region with strong connection to the orbitofrontal cortex showed a significant
correlation with spatial working memory accuracy in patients with first-episode
psychosis (r = .36, p < .05), whereas no significant correlation between these
variables was observed in the healthy control subjects. CONCLUSIONS: The observed
pattern of reduced microstructural complexity in the nuclei not only highlights
the involvement of the thalamus but also emphasizes the role of the higher-order
nuclei in the pathophysiology beginning in the early stage of schizophrenia.
PMID- 29961566
TI - The 2018 version of the gene table of monogenic neuromuscular disorders (nuclear
genome).
PMID- 29961565
TI - Endogenous Cell Type-Specific Disrupted in Schizophrenia 1 Interactomes Reveal
Protein Networks Associated With Neurodevelopmental Disorders.
AB - BACKGROUND: Disrupted in schizophrenia 1 (DISC1) has been implicated in a number
of psychiatric diseases along with neurodevelopmental phenotypes such as the
proliferation and differentiation of neural progenitor cells. While there has
been significant effort directed toward understanding the function of DISC1
through the determination of its protein-protein interactions within an in vitro
setting, endogenous interactions involving DISC1 within a cell type-specific
setting relevant to neural development remain unclear. METHODS: Using CRISPR/Cas9
(clustered regularly interspaced short palindromic repeats/CRISPR-associated
protein 9) genome engineering technology, we inserted an endogenous 3X-FLAG tag
at the C-terminus of the canonical DISC1 gene in human induced pluripotent stem
cells (iPSCs). We further differentiated these cells and used affinity
purification to determine protein-protein interactions involving DISC1 in iPSC
derived neural progenitor cells and astrocytes. RESULTS: We were able to
determine 151 novel cell type-specific proteins present in DISC1 endogenous
interactomes. The DISC1 interactomes can be clustered into several subcomplexes
that suggest novel DISC1 cell-specific functions. In addition, the DISC1
interactome in iPSC-derived neural progenitor cells associates in a connected
network containing proteins found to harbor de novo mutations in patients
affected by schizophrenia and contains a subset of novel interactions that are
known to harbor syndromic mutations in neurodevelopmental disorders. CONCLUSIONS:
Endogenous DISC1 interactomes within iPSC-derived human neural progenitor cells
and astrocytes are able to provide context to DISC1 function in a cell type
specific setting relevant to neural development and enables the integration of
psychiatric disease risk factors within a set of defined molecular functions.
PMID- 29961567
TI - Variants of Unknown Significance in Genes Associated with Heritable Thoracic
Aortic Disease Can Be Low Penetrant "Risk Variants".
AB - Thoracic aortic aneurysms leading to acute aortic dissections are a preventable
cause of premature deaths if individuals at risk can be identified. Individuals
with early-onset aortic dissections without a family history or syndromic
features have an increased burden of rare genetic variants of unknown
significance (VUSs) in genes with pathogenic variants for heritable thoracic
aortic disease (HTAD). We assessed the role of VUSs in the development of disease
using both in vitro enzymatic assays and mouse models. VUSs in LOX and MYLK
identified in individuals with acute aortic dissections were assayed to determine
whether they disrupted enzymatic activity. A subset of VUSs reduced enzymatic
activity compared to the wild-type proteins but less than pathogenic variants.
Additionally, a Myh11 variant, p.Arg247Cys, which does not cause aortic disease
in either humans or mice, was crossed with the Acta2-/- mouse, which has aortic
enlargement with age while Acta2+/- mice do not. Acta2+/-Myh11R247C/R247C mice
have aortic dilation by 3 months of age without medial degeneration, indicating
that two variants not known to cause disease do lead to aortic enlargement in
combination. Furthermore, the addition of Myh11R247C/R247C to the Acta2-/- mouse
model accelerates aortic enlargement and increases medial degeneration.
Therefore, our results emphasize the need for a classification system for
variants in Mendelian genes that goes beyond the 5-tier system of pathogenic,
likely pathogenic, VUS, likely benign, and benign, and includes a designation for
low-penetrant "risk variants" that trigger disease either in combination with
other risk factors or in a stochastic manner.
PMID- 29961569
TI - De Novo Missense Variants in TRAF7 Cause Developmental Delay, Congenital
Anomalies, and Dysmorphic Features.
AB - TRAF7 is a multi-functional protein involved in diverse signaling pathways and
cellular processes. The phenotypic consequence of germline TRAF7 variants remains
unclear. Here we report missense variants in TRAF7 in seven unrelated individuals
referred for clinical exome sequencing. The seven individuals share substantial
phenotypic overlap, with developmental delay, congenital heart defects, limb and
digital anomalies, and dysmorphic features emerging as key unifying features. The
identified variants are de novo in six individuals and comprise four distinct
missense changes, including a c.1964G>A (p.Arg655Gln) variant that is recurrent
in four individuals. These variants affect evolutionarily conserved amino acids
and are located in key functional domains. Gene-specific mutation rate analysis
showed that the occurrence of the de novo variants in TRAF7 (p = 2.6 * 10-3) and
the recurrent de novo c.1964G>A (p.Arg655Gln) variant (p = 1.9 * 10-8) in our
exome cohort was unlikely to have occurred by chance. In vitro analyses of the
observed TRAF7 mutations showed reduced ERK1/2 phosphorylation. Our findings
suggest that missense mutations in TRAF7 are associated with a multisystem
disorder and provide evidence of a role for TRAF7 in human development.
PMID- 29961570
TI - Deep Phenotyping on Electronic Health Records Facilitates Genetic Diagnosis by
Clinical Exomes.
AB - Integration of detailed phenotype information with genetic data is well
established to facilitate accurate diagnosis of hereditary disorders. As a rich
source of phenotype information, electronic health records (EHRs) promise to
empower diagnostic variant interpretation. However, how to accurately and
efficiently extract phenotypes from heterogeneous EHR narratives remains a
challenge. Here, we present EHR-Phenolyzer, a high-throughput EHR framework for
extracting and analyzing phenotypes. EHR-Phenolyzer extracts and normalizes Human
Phenotype Ontology (HPO) concepts from EHR narratives and then prioritizes genes
with causal variants on the basis of the HPO-coded phenotype manifestations. We
assessed EHR-Phenolyzer on 28 pediatric individuals with confirmed diagnoses of
monogenic diseases and found that the genes with causal variants were ranked
among the top 100 genes selected by EHR-Phenolyzer for 16/28 individuals (p < 2.2
* 10-16), supporting the value of phenotype-driven gene prioritization in
diagnostic sequence interpretation. To assess the generalizability, we replicated
this finding on an independent EHR dataset of ten individuals with a positive
diagnosis from a different institution. We then assessed the broader utility by
examining two additional EHR datasets, including 31 individuals who were
suspected of having a Mendelian disease and underwent different types of genetic
testing and 20 individuals with positive diagnoses of specific Mendelian
etiologies of chronic kidney disease from exome sequencing. Finally, through
several retrospective case studies, we demonstrated how combined analyses of
genotype data and deep phenotype data from EHRs can expedite genetic diagnoses.
In summary, EHR-Phenolyzer leverages EHR narratives to automate phenotype-driven
analysis of clinical exomes or genomes, facilitating the broader implementation
of genomic medicine.
PMID- 29961572
TI - Interleukin-6 receptor inhibition with tocilizumab induces a selective and
substantial increase in plasma IP-10 and MIP-1beta in non-ST-elevation myocardial
infarction.
AB - AIM: To evaluate the effect of interleukin-6 inhibition with tocilizumab on the
cytokine network in patients with acute non-ST-elevation myocardial infarction
(NSTEMI). METHODS: 117 patients with acute NSTEMI were randomised to an
intravenous infusion of 280 mg tocilizumab or placebo prior to coronary
angiography. Blood samples were obtained at baseline, at 6 consecutive points in
time during hospitalisation, and at follow-up after 3 and 6 months. Cytokines (n
= 27) were analysed with a multiplex cytokine assay. RESULTS: Using a mixed
between-within subjects analysis of variance, we observed a significant (p <
0.001) between-group difference in changes for interferon gamma-inducible protein
(IP-10) and macrophage inflammatory protein-1beta (MIP-1beta), due to significant
increases in the tocilizumab group during hospitalisation (i.e., IP-10 median
change from baseline during hospitalisation (mDelta), placebo: 3 (-60, 68) pg/ml
vs tocilizumab: 209 (69, 335) pg/ml; MIP-1beta mDelta, placebo: 5 (-2, 12) pg/ml
vs tocilizumab: 39 (24, 63) pg/ml). MIP-1beta was inversely correlated to
troponin T (r = -0.28, p < 0.05) and neutrophils (r = -0.32, p < 0.05) in the
tocilizumab group. In contrast, tocilizumab had only modest or no effects on the
other examined cytokines. CONCLUSIONS: Tocilizumab led to a selective and
substantial increase in IP-10 and MIP-1beta during the acute phase of NSTEMI,
with no or only minor effects on the other measured cytokines.
ClinicalTrials.gov, NCT01491074.
PMID- 29961571
TI - MPZL2, Encoding the Epithelial Junctional Protein Myelin Protein Zero-like 2, Is
Essential for Hearing in Man and Mouse.
AB - In a Dutch consanguineous family with recessively inherited nonsyndromic hearing
impairment (HI), homozygosity mapping combined with whole-exome sequencing
revealed a MPZL2 homozygous truncating variant, c.72del (p.Ile24Metfs*22). By
screening a cohort of phenotype-matched subjects and a cohort of HI subjects in
whom WES had been performed previously, we identified two additional families
with biallelic truncating variants of MPZL2. Affected individuals demonstrated
symmetric, progressive, mild to moderate sensorineural HI. Onset of HI was in the
first decade, and high-frequency hearing was more severely affected. There was no
vestibular involvement. MPZL2 encodes myelin protein zero-like 2, an adhesion
molecule that mediates epithelial cell-cell interactions in several (developing)
tissues. Involvement of MPZL2 in hearing was confirmed by audiometric evaluation
of Mpzl2-mutant mice. These displayed early-onset progressive sensorineural HI
that was more pronounced in the high frequencies. Histological analysis of adult
mutant mice demonstrated an altered organization of outer hair cells and
supporting cells and degeneration of the organ of Corti. In addition, we observed
mild degeneration of spiral ganglion neurons, and this degeneration was most
pronounced at the cochlear base. Although MPZL2 is known to function in cell
adhesion in several tissues, no phenotypes other than HI were found to be
associated with MPZL2 defects. This indicates that MPZL2 has a unique function in
the inner ear. The present study suggests that deleterious variants of
Mplz2/MPZL2 affect adhesion of the inner-ear epithelium and result in loss of
structural integrity of the organ of Corti and progressive degeneration of hair
cells, supporting cells, and spiral ganglion neurons.
PMID- 29961573
TI - Serum lipoprotein(a) is not modified by interleukin-6 receptor antagonism or
associated with inflammation in non-ST-elevation myocardial infarction.
AB - BACKGROUND: The IL-6 receptor antagonist tocilizumab has been shown to attenuate
the proatherogenic lipoprotein a [Lp(a)] in rheumatoid arthritis. We evaluated if
a single dose of tocilizumab reduced Lp(a) in patients with non-ST-elevation
myocardial infarction (NSTEMI). METHODS: Lp(a) was assessed by immunoassay (n =
117 patients) at 7 consecutive time-points between day 1 and 3 and at 3 and 6
months follow-up. RESULTS: Tocilizumab did not affect Lp(a) at any time-point
during the study and was not associated with cardiovascular risk factors.
CONCLUSIONS: Short-time inhibition of IL-6 with tocilizumab in patients with
NSTEMI did not influence Lp(a) levels.
PMID- 29961574
TI - Evolution of Cortical Neurogenesis in Amniotes Controlled by Robo Signaling
Levels.
AB - Cerebral cortex size differs dramatically between reptiles, birds, and mammals,
owing to developmental differences in neuron production. In mammals, signaling
pathways regulating neurogenesis have been identified, but genetic differences
behind their evolution across amniotes remain unknown. We show that direct
neurogenesis from radial glia cells, with limited neuron production, dominates
the avian, reptilian, and mammalian paleocortex, whereas in the evolutionarily
recent mammalian neocortex, most neurogenesis is indirect via basal progenitors.
Gain- and loss-of-function experiments in mouse, chick, and snake embryos and in
human cerebral organoids demonstrate that high Slit/Robo and low Dll1 signaling,
via Jag1 and Jag2, are necessary and sufficient to drive direct neurogenesis.
Attenuating Robo signaling and enhancing Dll1 in snakes and birds recapitulates
the formation of basal progenitors and promotes indirect neurogenesis. Our study
identifies modulation in activity levels of conserved signaling pathways as a
primary mechanism driving the expansion and increased complexity of the mammalian
neocortex during amniote evolution.
PMID- 29961575
TI - Direct Visualization of the Conformational Dynamics of Single Influenza
Hemagglutinin Trimers.
AB - Influenza hemagglutinin (HA) is the canonical type I viral envelope glycoprotein
and provides a template for the membrane-fusion mechanisms of numerous viruses.
The current model of HA-mediated membrane fusion describes a static "spring
loaded" fusion domain (HA2) at neutral pH. Acidic pH triggers a singular
irreversible conformational rearrangement in HA2 that fuses viral and cellular
membranes. Here, using single-molecule Forster resonance energy transfer (smFRET)
imaging, we directly visualized pH-triggered conformational changes of HA trimers
on the viral surface. Our analyses reveal reversible exchange between the pre
fusion and two intermediate conformations of HA2. Acidification of pH and
receptor binding shifts the dynamic equilibrium of HA2 in favor of forward
progression along the membrane-fusion reaction coordinate. Interaction with the
target membrane promotes irreversible transition of HA2 to the post-fusion state.
The reversibility of HA2 conformation may protect against transition to the post
fusion state prior to arrival at the target membrane.
PMID- 29961576
TI - Recovering Gene Interactions from Single-Cell Data Using Data Diffusion.
AB - Single-cell RNA sequencing technologies suffer from many sources of technical
noise, including under-sampling of mRNA molecules, often termed "dropout," which
can severely obscure important gene-gene relationships. To address this, we
developed MAGIC (Markov affinity-based graph imputation of cells), a method that
shares information across similar cells, via data diffusion, to denoise the cell
count matrix and fill in missing transcripts. We validate MAGIC on several
biological systems and find it effective at recovering gene-gene relationships
and additional structures. Applied to the epithilial to mesenchymal transition,
MAGIC reveals a phenotypic continuum, with the majority of cells residing in
intermediate states that display stem-like signatures, and infers known and
previously uncharacterized regulatory interactions, demonstrating that our
approach can successfully uncover regulatory relations without perturbations.
PMID- 29961568
TI - De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with
Seizures.
AB - Next-generation sequencing has been invaluable in the elucidation of the genetic
etiology of many subtypes of intellectual disability in recent years. Here, using
exome sequencing and whole-genome sequencing, we identified three de novo
truncating mutations in WAS protein family member 1 (WASF1) in five unrelated
individuals with moderate to profound intellectual disability with autistic
features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex
and acts as a mediator between Rac-GTPase and actin to induce actin
polymerization. The three mutations connected by Matchmaker Exchange were
c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T
(p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants
are predicted to partially or fully disrupt the C-terminal actin-binding WCA
domain. Functional studies using fibroblast cells from two affected individuals
with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin
remodeling. This study provides evidence that de novo heterozygous mutations in
WASF1 cause a rare form of intellectual disability.
PMID- 29961578
TI - Defects in the Alternative Splicing-Dependent Regulation of REST Cause Deafness.
AB - The DNA-binding protein REST forms complexes with histone deacetylases (HDACs) to
repress neuronal genes in non-neuronal cells. In differentiating neurons, REST is
downregulated predominantly by transcriptional silencing. Here we report that
post-transcriptional inactivation of REST by alternative splicing is required for
hearing in humans and mice. We show that, in the mechanosensory hair cells of the
mouse ear, regulated alternative splicing of a frameshift-causing exon into the
Rest mRNA is essential for the derepression of many neuronal genes. Heterozygous
deletion of this alternative exon of mouse Rest causes hair cell degeneration and
deafness, and the HDAC inhibitor SAHA (Vorinostat) rescues the hearing of these
mice. In humans, inhibition of the frameshifting splicing event by a novel REST
variant is associated with dominantly inherited deafness. Our data reveal the
necessity for alternative splicing-dependent regulation of REST in hair cells,
and they identify a potential treatment for a group of hereditary deafness cases.
PMID- 29961577
TI - A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion
like RNA Binding Proteins.
AB - Proteins such as FUS phase separate to form liquid-like condensates that can
harden into less dynamic structures. However, how these properties emerge from
the collective interactions of many amino acids remains largely unknown. Here, we
use extensive mutagenesis to identify a sequence-encoded molecular grammar
underlying the driving forces of phase separation of proteins in the FUS family
and test aspects of this grammar in cells. Phase separation is primarily governed
by multivalent interactions among tyrosine residues from prion-like domains and
arginine residues from RNA-binding domains, which are modulated by negatively
charged residues. Glycine residues enhance the fluidity, whereas glutamine and
serine residues promote hardening. We develop a model to show that the measured
saturation concentrations of phase separation are inversely proportional to the
product of the numbers of arginine and tyrosine residues. These results suggest
it is possible to predict phase-separation properties based on amino acid
sequences.
PMID- 29961579
TI - Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor
Microenvironment.
AB - Knowledge of immune cell phenotypes in the tumor microenvironment is essential
for understanding mechanisms of cancer progression and immunotherapy response. We
profiled 45,000 immune cells from eight breast carcinomas, as well as matched
normal breast tissue, blood, and lymph nodes, using single-cell RNA-seq. We
developed a preprocessing pipeline, SEQC, and a Bayesian clustering and
normalization method, Biscuit, to address computational challenges inherent to
single-cell data. Despite significant similarity between normal and tumor tissue
resident immune cells, we observed continuous phenotypic expansions specific to
the tumor microenvironment. Analysis of paired single-cell RNA and T cell
receptor (TCR) sequencing data from 27,000 additional T cells revealed the
combinatorial impact of TCR utilization on phenotypic diversity. Our results
support a model of continuous activation in T cells and do not comport with the
macrophage polarization model in cancer. Our results have important implications
for characterizing tumor-infiltrating immune cells.
PMID- 29961580
TI - High-Throughput Investigation of Diverse Junction Elements in RNA Tertiary
Folding.
AB - RNAs fold into defined tertiary structures to function in critical biological
processes. While quantitative models can predict RNA secondary structure
stability, we are still unable to predict the thermodynamic stability of RNA
tertiary structure. Here, we probe conformational preferences of diverse RNA two
way junctions to develop a predictive model for the formation of RNA tertiary
structure. We quantitatively measured tertiary assembly energetics of >1,000 of
RNA junctions inserted in multiple structural scaffolds to generate a
"thermodynamic fingerprint" for each junction. Thermodynamic fingerprints enabled
comparison of junction conformational preferences, revealing principles for how
sequence influences 3-dimensional conformations. Utilizing fingerprints of
junctions with known crystal structures, we generated ensembles for related
junctions that predicted their thermodynamic effects on assembly formation. This
work reveals sequence-structure-energetic relationships in RNA, demonstrates the
capacity for diverse compensation strategies within tertiary structures, and
provides a path to quantitative modeling of RNA folding energetics based on
"ensemble modularity."
PMID- 29961582
TI - Response to Spartalis et al.
PMID- 29961581
TI - Radiotherapy dose-volume parameters predict videofluoroscopy-detected dysphagia
per DIGEST after IMRT for oropharyngeal cancer: Results of a prospective
registry.
AB - PURPOSE: Our primary aim was to prospectively validate retrospective dose
response models of chronic radiation-associated dysphagia (RAD) after intensity
modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim
was to validate a grade >=2 cut-point of the published videofluoroscopic
dysphagia severity (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as
radiation dose-dependent. MATERIAL AND METHODS: Ninety-seven patients enrolled on
an IRB-approved prospective registry protocol with stage I-IV OPC underwent pre-
and 3-6 month post-RT videofluoroscopy. Dose-volume histograms (DVH) for
swallowing regions of interest (ROI) were calculated. Dysphagia severity was
graded per DIGEST criteria (dichotomized with grade >=2 as moderate/severe RAD).
Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC)
were used to identify dose-volume effects associated with moderate/severe RAD.
RESULTS: 31% developed moderate/severe RAD (i.e. DIGEST grade >=2) at 3-6 months
after RT. RPA found DVH-derived dosimetric parameters of geniohyoid/mylohyoid
(GHM), superior pharyngeal constrictor (SPC), and supraglottic region were
associated with DIGEST grade >=2 RAD. V61 >= 18.57% of GHM demonstrated optimal
model performance for prediction of DIGEST grade >=2. CONCLUSION: The findings
from this prospective longitudinal registry validate prior observations that dose
to submental musculature predicts for increased burden of dysphagia after
oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade >=2 as
a dose-dependent split for use as an endpoint in trials or predictive dose
response analysis of videofluoroscopy results.
PMID- 29961583
TI - Fatigue evaluation of long cortical bone using ultrasonic guided waves.
AB - Bone fatigue fracture is a progressive disease due to stress concentration. This
study aims to evaluate the long bone fatigue damage using the ultrasonic guided
waves. Two-dimensional finite-difference time-domain method was employed to
simulate the ultrasonic guided wave propagation in the long bone under different
elastic modulus. The experiment was conducted on a 3.8 mm-thick bovine bone
plate. The phase velocities of two fundamental guided modes, A1 and S1, were
measured by using the axial transmission technique. Simulation shows that the
phase velocities of guided modes A1 and S1 decrease with the increasing of the
fatigue damage. After 20,000 cycles of fatigue loading on the bone plate, the
average phase velocities of A1 and S1 modes were 6.6% and 5.3% respectively,
lower than those of the intact bone. The study suggests that ultrasonic guided
waves can be potentially used to evaluate the fatigue damage in long bones.
PMID- 29961584
TI - Effects of reproduction on sexual dimorphisms in rat bone mechanics.
AB - Osteoporosis most commonly affects postmenopausal women. Although men are also
affected, women over 65 are 6 times more likely to develop osteoporosis than men
of the same age. This is largely due to accelerated bone remodeling after
menopause; however, the peak bone mass attained during young adulthood also plays
an important role in osteoporosis risk. Multiple studies have demonstrated sexual
dimorphisms in peak bone mass, and additionally, the female skeleton is
significantly altered during pregnancy/lactation. Although clinical studies
suggest that a reproductive history does not increase the risk of developing
postmenopausal osteoporosis, reproduction has been shown to induce long-lasting
alterations in maternal bone structure and mechanics, and the effects of
pregnancy and lactation on maternal peak bone quality are not well understood.
This study compared the structural and mechanical properties of male, virgin
female, and post-reproductive female rat bone at multiple skeletal sites and at
three different ages. We found that virgin females had a larger quantity of
trabecular bone with greater trabecular number and more plate-like morphology,
and, relative to their body weight, had a greater cortical bone size and greater
bone strength than males. Post-reproductive females had altered trabecular
microarchitecture relative to virgins, which was highly similar to that of male
rats, and showed similar cortical bone size and bone mechanics to virgin females.
This suggests that, to compensate for future reproductive bone losses, females
may start off with more trabecular bone than is mechanically necessary, which may
explain the paradox that reproduction induces long-lasting changes in maternal
bone without increasing postmenopausal fracture risk.
PMID- 29961585
TI - Discussion.
PMID- 29961586
TI - Introducing the concept of semielective lung transplantation through the use of
ex vivo lung perfusion.
PMID- 29961587
TI - Who should be "let in" when managing the thoracic outlet?
PMID- 29961589
TI - The value of long-term postoperative quality of life and patient-centered
decision-making: What is at stake?
PMID- 29961588
TI - An in vitro evaluation of turbulence after transcatheter aortic valve
implantation.
AB - BACKGROUND: This study aimed at assessment of post-transcatheter aortic valve
(TAV) replacement hemodynamics and turbulence when a same-size SAPIEN 3 (Edwards
Lifesciences Corp, Irvine, Calif) and Medtronic Evolut (Minneapolis, Minn) were
implanted in a rigid aortic root with physiological dimensions and in a
representative root with calcific leaflets obtained from patient computed
tomography scans. METHODS: TAV hemodynamics were studied by placing a SAPIEN 3 26
mm and an Evolut 26-mm in rigid aortic roots and representative root with
calcific leaflets under physiological conditions. Hemodynamics were assessed
using high-fidelity particle image velocimetry and high-speed imaging.
Transvalvular pressure gradients (PGs), pinwheeling indices, and Reynolds shear
stress (RSS) were calculated. RESULTS: (1) PGs obtained with the Evolut and the
SAPIEN 3 were comparable among the different models (10.5 +/- 0.15 mm Hg vs 7.76
+/- 0.083 mm Hg in the rigid model along with 13.9 +/- 0.19 mm Hg vs 5.0 +/- 0.09
mm Hg in representative root with calcific leaflets obtained from patient
computed tomography scans respectively); (2) more pinwheeling was found in the
SAPIEN 3 than the Evolut (0.231 +/- 0.057 vs 0.201 +/- 0.05 in the representative
root with calcific leaflets and 0.366 +/- 0.067 vs 0.122 +/- 0.045 in the rigid
model); (3) higher rates of RSS were found in the Evolut (161.27 +/- 3.45 vs
122.84 +/- 1.76 Pa in representative root with calcific leaflets and 337.22 +/-
7.05 vs 157.91 +/- 1.80 Pa in rigid models). More lateral fluctuations were found
in representative root with calcific leaflets. CONCLUSIONS: (1) Comparable PGs
were found among the TAVs in different models; (2) pinwheeling indices were found
to be different between both TAVs; (3) turbulence patterns among both TAVs
translated according to RSS were different. Rigid aortic models yield more
conservative estimates of turbulence; (4) both TAVs exhibit peak maximal RSS that
exceeds platelet activation 100 Pa threshold limit.
PMID- 29961590
TI - Computed tomography features of resected lung adenocarcinomas with spread through
air spaces.
AB - BACKGROUND: Spread through air spaces (STAS) is a recently recognized invasive
pattern of lung cancer defined as "micropapillary clusters, solid nests, or
single cells beyond the edge of the tumor into air spaces." Since STAS has been
shown to be a significant prognosticator for the postoperative survival,
predicting STAS preoperatively by computed tomography (CT) might help determine
the optimum surgical procedures. METHODS: Information on STAS and preoperative CT
was available in 327 patients with resected lung adenocarcinomas. STAS was
defined as tumor cells within air spaces in the lung parenchyma beyond the edge
of the main tumor. The association of STAS with CT characteristics, such as
vascular convergence, ground-glass opacity (GGO), air bronchogram, notch, pleural
indentation, spiculation, and cavitation, was analyzed. RESULTS: Among the 327
patients with resected adenocarcinoma, 191 (58.4%) were positive for STAS. A
univariable analysis demonstrated that STAS-positive adenocarcinomas were
significantly associated with a larger radiologic tumor diameter (P = .02), the
presence of vascular convergence (P < .01), notch (P < .01), pleural indentation
(P = .03), spiculation (P < .01), and the absence of GGO (P < .01) compared with
STAS-negative ones. In a multivariable analysis, the presence of notch (P = .01)
and the absence of GGO (P < .01) were shown to be significantly associated with
the STAS phenomenon. The odds ratio for STAS of notch-positive and GGO-negative
adenocarcinomas against notch-negative and GGO-positive ones was 5.01 (P < .01).
CONCLUSIONS: The presence of notch and the absence of GGO were independently
associated with the STAS phenomenon. These results will prove helpful in
identifying STAS-positive adenocarcinoma by CT before surgical resection.
PMID- 29961591
TI - Chest wall reconstruction with 3-dimensional custom-made carbon fiber ribs.
PMID- 29961592
TI - Comparative effectiveness of coronary artery bypass grafting versus percutaneous
coronary intervention in a real-world Surgical Treatment for Ischemic Heart
Failure trial population.
AB - OBJECTIVE: There are no prospective randomized trial data to guide decisions on
optimal revascularization strategies for patients with multivessel coronary
artery disease and reduced ejection fraction. In this analysis, we describe the
comparative effectiveness of coronary artery bypass grafting (CABG) versus
percutaneous coronary intervention (PCI) in this patient population. METHODS: A
multicenter, retrospective analysis of all CABG (n = 18,292) and PCIs (n =
55,438) performed from 2004 to 2014 among 7 medical centers reporting to the
Northern New England Cardiovascular Disease Study Group. After applying inclusion
and exclusion criteria from the Surgical Treatment for Ischemic Heart Failure
trial, there were 955 CABG and 718 PCI patients with an ejection fraction <= 35%
and 2- or 3-vessel disease. Inverse probability weighting was used for risk
adjustment. The primary end point was all-cause mortality. Secondary end points
included rates of 30-day mortality, stroke, acute kidney injury, and incidence of
repeat revascularization. RESULTS: The median duration of follow-up was 4.3 years
(range, 1.59-6.71 years). CABG was associated with improved long-term survival
compared with PCI after risk adjustment (hazard ratio, 0.59; 95% confidence
interval, 0.50-0.71; P < .01). Although CABG and PCI had similar 30-day mortality
rates (P = .14), CABG was associated with a higher frequency of stroke (P < .001)
and acute kidney injury (P < .001), whereas PCI was associated with a higher
incidence of repeat revascularization (P < .001). CONCLUSIONS: Among patients
with reduced ejection fraction and multivessel disease, CABG was associated with
improved long-term survival compared with PCI. CABG should be strongly considered
in patients with ischemic cardiomyopathy and multivessel coronary disease.
PMID- 29961593
TI - Residual pulmonary hypertension after pulmonary endarterectomy: What is there
more than meets the eye?
PMID- 29961594
TI - A lesson in the power of observation.
PMID- 29961595
TI - Beyond #ILookLikeASurgeon.
PMID- 29961596
TI - Does Neuroscience Leave Room for Free Will?
AB - A reductively mechanistic approach to neuroscience suggests that low-level
physical laws determine our actions and that mental states are epiphenomena. In
this scheme there seems to be little room for free will or genuine agency. I
argue here that physical indeterminacy provides room for the information entailed
in patterns of neuronal firing - the mental content of beliefs, goals, and
intentions - to have real causal power in decision-making.
PMID- 29961597
TI - Retained foreign bodies and associated risk factors and outcomes in pediatric
surgical patients.
AB - BACKGROUND: Retained foreign bodies discovered after surgery are documented as
Agency for Health Care Quality and Research Patient Safety Indicators. Our goal
was to identify pediatric patient and procedure risk factors and outcomes
associated with RFB based on AHRQ Definitions. METHODS: We performed a
retrospective case-control study of children with RFB using the PHIS database.
Patients were defined as having RFB based on the AHRQ PSI definition. Controls
were matched in a 5:1 ratio on age, procedure date, and hospital. Our primary
outcome was the presence of RFB. Secondary outcomes included hospital length of
stay and mortality. RESULTS: Patients with RFB often underwent emergent
procedures, experienced one or more chronic conditions, and required ICU
admission or mechanical ventilation. Musculoskeletal procedures contribute the
largest numbers of RFB (30.4%), but interventional radiology procedures had
higher odds of having RFB (AOR 7.88, p < 0.0001). After multivariate adjustment,
children with RFB required 4 more days of hospitalization (p < .001), but there
was no difference in mortality (p = .579). CONCLUSIONS: The implications of our
study include identifying which administrative flags can be used to identify
children at higher risks for RFB. Early identification of at-risk patients and
prevention are key towards addressing the primary problem and corresponding
sequela of RFB. LEVELS OF EVIDENCE: Prognostic Study Level III.
PMID- 29961598
TI - Concerning "Comments and question on "Selective inhibition of endothelial NF-kB
signaling attenuates chronic intermittent hypoxia-induced atherosclerosis in
mice" ".
PMID- 29961599
TI - Universal screening of children for familial hypercholesterolaemia: Value for
money?
PMID- 29961600
TI - Unlocking the secrets of high-risk lipid rich plaque: Are we there?
PMID- 29961601
TI - Depression: A cognitive perspective.
AB - Cognitive science has been instrumental in advancing our understanding of the
onset, maintenance, and treatment of depression. Research conducted over the last
50 years supports the proposition that depression and risk for depression are
characterized by the operation of negative biases, and often by a lack of
positive biases, in self-referential processing, interpretation, attention, and
memory, as well as the use of maladaptive cognitive emotion regulation
strategies. There is also evidence to suggest that deficits in cognitive control
over mood-congruent material underlie these cognitive processes. Specifically,
research indicates that difficulty inhibiting and disengaging from negative
material in working memory: (1) increases the use of maladaptive emotion
regulation strategies (e.g., rumination), decreases the use of adaptive emotion
regulation strategies (e.g., reappraisal), and potentially impedes flexible
selection and implementation of emotion regulation strategies; (2) is associated
with negative biases in attention; and (3) contributes to negative biases in long
term memory. Moreover, studies suggest that these cognitive processes exacerbate
and sustain the negative mood that typifies depressive episodes. In this review,
we present evidence in support of this conceptualization of depression and
discuss implications of research findings for theory and practice. Finally, we
advance directions for future research.
PMID- 29961602
TI - GM-CSF improves the immune response to the diphtheria-component in a multivalent
vaccine.
AB - Multivalent tetanus and diphtheria toxoid containing vaccines belong to the most
frequently applied vaccines. However, there is an imbalance in the degree of
protection against the two antigens with insufficient long-term protection
against diphtheria, particularly in the elderly population. We have previously
reported a positive correlation between granulocyte macrophage-colony stimulating
factor (GM-CSF) and the production of diphtheria-specific antibodies. Therefore,
in the present study we analyzed the effects of in vivo applied recombinant GM
CSF on immunization with multivalent tetanus/diphtheria vaccine in mice of
different age. In vivo application of GM-CSF lead to enhanced production of
diphtheria-specific antibodies as well as more diphtheria-specific CD4+ T cells
following vaccination with multivalent tetanus/diphtheria vaccine. In contrast,
the humoral and cellular immune response to the tetanus component was unaltered.
Furthermore, application of GM-CSF resulted in more splenic CD11b+ dendritic
cells (DCs) with a higher MHC-II expression. GM-CSF also induced a stronger
recruitment of CD11b+ DCs to the injected muscle. Most remarkably, GM-CSF was
able to boost the diphtheria-specific immune response to the multivalent vaccine
in aged mice. This study demonstrates that local administration of GM-CSF is able
to improve immune responsiveness to the diphtheria component of multivalent
tetanus/diphtheria vaccine in young and old mice. This information could be
useful for the future design of vaccines for the elderly.
PMID- 29961603
TI - The economic burden of human papillomavirus infection-associated diseases in the
Republic of Korea, 2002-2015.
AB - BACKGROUND: This prevalence-based, cost-of-illness study estimated the health
care costs of human papillomavirus (HPV) infection-associated diseases in the era
before the introduction of organized HPV vaccination for 12-year-old girls in
2016, South Korea. METHODS: The claims data provided by the National Health
Insurance Service was used to estimate the prevalence of HPV-associated diseases
and their direct medical costs, including costs related to hospitalizations,
outpatient visits, and medications. RESULTS: A total of 1.3 million men and women
used medical services for HPV-attributed diseases between 2002 and 2015. Among
women, the most common diseases attributable to HPV were cervical dysplasia
(64.4%), anogenital warts (12.9%), cervical carcinoma in situ (10.7%) and
cervical cancer (2.6%), whereas anogenital warts (80.6%), benign neoplasms of
larynx (14.3%), and anal cancers (8.9%) were most common among men. In 2015, the
healthcare cost attributable to HPV was 124.9 million US dollars (USD)
representing 69.0% of the annual cost of all HPV-associated diseases. At a cost
of 75.1 million USD, cervical cancer contributed the largest economic burden in
2015 followed by cervical dysplasia (19.4 million USD) and cervical carcinoma in
situ (10.7 million USD). These three conditions represented 58.2% of the total
annual cost of all HPV-associated diseases, while 84.2% of the total annual cost
was attributable to HPV. Annual health care costs increased from 42.6 million USD
in 2002 to 180.9 million USD in 2015. CONCLUSION: The healthcare costs associated
with HPV-related diseases in Korea are substantial and increased between 2002 and
2015 mainly caused by increased number of patients. Expanding the target age for
HPV vaccination of girls and introducing HPV vaccination for boys are possible
ways of reducing the economic burden of HPV-associated disease and should be
considered.
PMID- 29961604
TI - Meningococcal disease burden and transmission in crowded settings and mass
gatherings other than Hajj/Umrah: A systematic review.
AB - BACKGROUND: Mass gatherings (MGs) such as the Hajj and Umrah pilgrimages are
known to amplify the risk of invasive meningococcal disease (IMD) due to enhanced
transmission of the organism between attendees. The burden of IMD at MGs other
than Hajj and Umrah has not previously been quantified through a systematic
review. METHODS: A systematic search for relevant articles in PubMed and Embase
was conducted using MeSH terms; this was buttressed by hand searching. Following
data abstraction, a narrative synthesis was conducted to quantify the burden of
IMD at MGs and identify potential risk factors and mitigation measures. RESULTS:
Thirteen studies reporting occurrence of IMD at MGs or similar crowded settings
were identified. Eight studies reported cases or outbreaks in MGs of >=1000
people; five others reported IMD in other crowded settings; all occurred between
1991 and 2015. All age groups were involved in the identified studies; however
the majority of cases (~80%) were young people aged 15-24 years. The number of
affected people ranged from one to 321 cases and the overall crude estimate of
incidence was calculated as 66 per 100,000 individuals. Serogroups A, C, B and W
were identified, with serogroups A and C being most common. Of 450 cases of IMD
reported in non-Hajj/Umrah MGs, 67 (14.9%) had fatal outcomes. CONCLUSION: IMD
outbreaks at non-Hajj/Umrah MGs are generally much smaller than Hajj-related
outbreaks and affect mainly young people. Health education and vaccination should
be considered for attendees of high risk non-Hajj/Umrah MGs, especially those
involving adolescents and young adults.
PMID- 29961605
TI - DNA prime/MVTT boost regimen with HIV-1 mosaic Gag enhances the potency of
antigen-specific immune responses.
AB - HIV-1 diversity and latent reservoir are the major challenges for the development
of an effective AIDS vaccine. It is well indicated that Gag-specific CD8+ T cells
serve as the dominant host immune surveillance for HIV-1 control, but it still
remains a challenge for vaccine design to induce broader and stronger cytotoxic T
cell immunity against the virus. Genetic variation of the HIV-1 gag gene across
different clades is one of the reasons for the reduction of antigenic epitope
coverage. Here, we report an immunization strategy with heterologous vaccines
expressing a mosaic Gag antigen aimed to increase antigenic breadth against a
wider spectrum of HIV-1 strains. Priming using a DNA vaccine via in vivo
electroporation, followed by boosting with a live replication-competent modified
vaccinia TianTan (MVTT) vectored vaccine, elicited greater and broader protective
Gag-specific immune responses in mice. Compared to DNA or MVTT homologous
immunization, the heterologous DNA/MVTT vaccination resulted in higher
frequencies of broadly reactive, Gag-specific, polyfunctional, long-lived
cytotoxic CD8+ T cells, as well as increased anti-Gag antibody titer.
Importantly, the DNA/MVTT heterologous vaccination induced protection against
EcoHIV and mesothelioma AB1-Gag challenges. In summary, the stronger protective
Gag-specific immunity induced by the heterologous regimen using two safe vectors
shows promise for further development to enhance anti-HIV-1 immunity. Our study
has important implications for immunogen design and the development of an
effective HIV-1 heterologous vaccination strategy.
PMID- 29961607
TI - [Promoting Health Promotion: Medical students perceptions about an educational
program on behavioral change in primary care].
AB - OBJECTIVE: To evaluate whether a training program offered by family physicians in
the official medical curriculum on principles and strategies to help patients
change risk behaviours (HPCRB), produces changes in perceptions, opinions, and
attitudes regarding this type of intervention. DESIGN: Quasi-experimental before
after study. SETTING: A School of Medicine. PARTICIPANTS: All students in their
4th year (n=110). INTERVENTIONS: Experiential training course on communicative
strategies for HPCRB. MEASUREMENTS: Opinions and perceptions were evaluated
before and after the course using an ad hoc survey. RESULTS: After the course,
students (n=103) changed their ideas about motivation as an 'internal' (15, 13%)
to 'internal-external' factor (71, 61%) (P=.003), reinforcing their opinions
about the clinician's ability for HPCRB (high: 72, 62%; low: 10, 12%; P=.008).
They considered themselves more capable to respect patient autonomy when they
make decisions or follow harmful behaviours (easy: 58, 50%; difficult: 28, 24%;
P=.001), and increased their perception of their ability to cope with this type
of interview (83, 72% vs. 1, 1%; P<.001). CONCLUSIONS: This training course seems
to contribute to creating positive perceptions and attitudes in students, as
regards key aspects when conducting an interview for HPCRB. This is a key
preliminary aspect to implement this type of strategy.
PMID- 29961606
TI - Randomized trial comparing the safety and antibody responses to live attenuated
versus inactivated influenza vaccine when administered to breastfeeding women.
AB - BACKGROUND: Live attenuated influenza vaccine (LAIV) and inactivated influenza
vaccine (IIV) are both licensed for administration to nursing mothers. Little is
known about the potential for transmission of LAIV viruses from the mother to the
infant and the comparative breast milk antibody responses to LAIV and IIV.
METHODS: We performed a randomized, double-blind study comparing the
immunogenicity of LAIV to IIV when administered to nursing mothers. The safety of
LAIV to IIV in women and their infants was also compared. Women received LAIV +
intramuscular placebo, or IIV + intranasal placebo on Day 0. Breast milk and
nasal swabs (from women and infants) were collected on Days 0, 2, and 8 for
detection of LAIV. Breast milk and serum antibody responses were measured at Days
0 and 28. The primary hypothesis was that LAIV would provide superior induction
of breast milk IgA responses to influenza as compared to IIV when administered to
nursing mothers. RESULTS: Breast milk IgG, breast milk IgA (H1N1 only), serum
hemagglutination inhibition (HAI), and serum IgG responses were significantly
higher following administration of IIV compared to LAIV. Receipt of either LAIV
or IIV was safe in women and their infants. One (1%) LAIV recipient transmitted
vaccine virus to her infant who remained well. No influenza virus was detected in
breast milk. CONCLUSIONS: Breast milk and serum antibody responses were higher
for IIV compared to LAIV. LAIV and IIV were safe for nursing women but there was
one (1%) possible transmission of LAIV to an infant. This study suggests that IIV
may be the preferred vaccine for nursing mothers.
PMID- 29961608
TI - Mannose Binding Lectin and Pentraxin 3 in Patients with Diabetic Retinopathy.
AB - BACKGROUND: Mannose binding lectin (MBL) is a protein of the complement system
and pentraxin-3 (PTX3) is an acute phase protein both with an important role in
inflammatory diseases, such as diabetic retinopathy (DR). AIM OF THE STUDY: To
evaluate whether plasma MBL and PTX3 levels are associated with the development
of DR and if patients with and without DR can be distinguished. METHODS: The
patients were divided into three groups: diabetic without DR; with mild/moderate
DR, and with severe/proliferative DR. PTX3 and MBL levels were measured with
enzyme-linked immunosorbent assay kits. RESULTS: A total of 74 patients were
included. A significant association was observed between high levels of MBL and
severe DR; 47% of patients with severe/proliferative DR had high levels of MBL,
whereas 12% of the patients with diabetes but no DR had high levels of MBL (p =
0.008; odds ratio [OR]: 6.06; 95% confidence interval [CI]: 1.4-25.0). High
levels of MBL were more frequent in patients with severe/proliferative disease
(47%) when compared to those with mild/moderate DR (20%), p = 0.04 (OR: 3.46; 95%
CI: 1.0-11.8). PTX3 levels were similar among the groups and were not related to
the development or severity of DR. CONCLUSION: We found a significant association
between high plasma MBL levels and DR development as well as with
severe/proliferative DR. We observed no relationship between plasma PTX3 levels
and the development or severity of DR.
PMID- 29961609
TI - Contour correction for stock titanium healing abutments.
PMID- 29961610
TI - Evaluation of the trueness and tissue surface adaptation of CAD-CAM mandibular
denture bases manufactured using digital light processing.
AB - STATEMENT OF PROBLEM: Studies assessing the trueness and tissue surface
adaptation of computer-aided design and computer-aided manufacturing (CAD-CAM)
mandibular complete denture bases fabricated using digital light processing (DLP)
are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the
trueness of DLP-generated denture bases and to compare the tissue surface
adaptation of DLP with milling and pack and press. MATERIAL AND METHODS: The
mandibular denture bases were virtually designed on a reference cast and were
fabricated using DLP. Their intaglio surfaces were scanned and superimposed on
the reference CAD denture base to evaluate the trueness. The reference cast was
duplicated to create 10 identical master casts that were scanned to design 10
virtual denture bases. Twenty denture bases were fabricated with DLP and milling
(10 specimens per technique). In addition, 10 denture bases were fabricated with
the pack and press technique. The intaglio surfaces of the denture bases were
scanned and superimposed on the corresponding master casts to compare tissue
surface adaptation among the 3 techniques. The Mann-Whitney test and Kruskal
Wallis analysis of variance (alpha=.05) were used for statistical analyses.
RESULTS: For trueness, the milled denture base was better than the DLP denture
base (P<.001). However, no statistically significant difference was detected with
respect to tissue surface adaptation of the denture base, regardless of the
fabrication technique (P>.05). The DLP denture base showed comparable tissue
surface adaptation with the milled base, one with a small interquartile range.
CONCLUSIONS: The intaglio surfaces of DLP and milled denture bases corresponded
within a 100-MUm accuracy compared with the master cast. Although the DLP denture
base exhibited tissue compression on the ridge crest, it showed comparable tissue
adaptation to the milled denture base.
PMID- 29961611
TI - Effect of silica-containing glass-ceramic liner treatment on zirconia coping
retention.
AB - STATEMENT OF PROBLEM: Zirconia prostheses show a high rate of retention loss, and
more information is needed regarding the treatment of the intaglios of zirconia
prostheses to improve the bond strength between zirconia and resin cement.
PURPOSE: The purpose of this in vitro study was to evaluate the retention of
titanium abutments and zirconia prostheses treated with silica-containing glass
ceramic liners. The effect of the abutment convergence angle on retention force
was also examined. MATERIAL AND METHODS: Titanium abutments and zirconia copings
(n=90) were fabricated with 3 different convergence angles (6, 12, and 24
degrees). Specimens were divided into 2 groups according to surface treatment: an
airborne-particle-abraded control group and a group that was coated with a silica
containing glass-ceramic liner after airborne-particle abrasion (liner group).
The thickness of the liner was measured, and the inner spacing of the zirconia
coping was modified in the liner group. The coping was cemented, and the
retention was evaluated with a tensile bond strength test by using a universal
testing machine. Retention was analyzed by using a 2-way analysis of variance.
Modes of failure were evaluated by examining the fracture surface. Elemental
analysis of the interface was also performed. RESULTS: The liner group showed a
significantly higher retention force for the zirconia prosthesis (P<.05).
Regardless of surface treatment, the retention force at a convergence angle of 6
degrees was higher than that at 24 degrees (P<.05). The control group showed
mostly adhesive type failures, whereas the liner group exhibited mostly mixed
type failures. CONCLUSIONS: Silica-containing glass-ceramic liner treatment
increased the retention compared with airborne-particle abrasion treatment alone.
Tensile bond strength increased with decreasing abutment convergence angle.
PMID- 29961612
TI - Digital design and 3D printing of an implant-supported prosthetic stent for
protecting complete arch soft tissue grafts around dental implants: A dental
technique.
AB - A method for digital fabrication of an implant-supported soft tissue graft stent
to protect, shape, and ensure intimate adaptation of the complete arch graft to
the periosteum surrounding dental implants is described. To fabricate the stent,
an extraoral scanner was used to convert the implant cast into digital data.
Dental design software was then used to fabricate the stent, which is produced by
3-dimensional (3D) printing. Due to the lack of long-term biocompatible 3D
printing material, the stent was duplicated in bisacryl resin. The patient
reported more comfort and stability with the implant-supported stent than the
conventional stent received following a previous debulking surgical procedure.
PMID- 29961613
TI - Retrofitting a foundation restoration to an existing ceramic crown after
endodontic treatment: A dental technique.
AB - This article describes the fabrication of a foundation restoration after
endodontic treatment using a preexisting ceramic prosthesis and
polytetrafluoroethylene (PTFE) tape as a barrier. This technique presents a
solution if the prosthesis and marginal integrity are to be maintained.
PMID- 29961614
TI - In vitro retention of prefabricated and individually formed posts: A pilot study.
AB - STATEMENT OF PROBLEM: Data on the retention of individually formed fiber
reinforced composite posts (everStick) cemented with self-adhesive cement are
lacking. PURPOSE: The purpose of this in vitro study was to investigate the pull
out strength of 2 different fiber-reinforced composite posts (prefabricated and
individually formed) cemented into extracted teeth with self-adhesive resin
cement. MATERIAL AND METHODS: Thirty extracted single-rooted human teeth were
decoronated, endodontically treated, and prepared with post spaces of equal
length. Prepared specimens were divided into 2 groups (n=15 each) based on the
type of post: commercially prefabricated fiber posts (GC) and individually formed
resin posts (using GC reinforcing fibers). Self-adhesive resin cement (G-CEM
LinkAce; GC) was used to cement all posts. Each post was held with moderate
pressure, and root surfaces were light polymerized for 20 seconds (650 mW/cm2).
After cementation, the specimens were stored in saline solution for 30 days.
Treated teeth were kept in water for 24 hours before pull-out testing parallel to
the longitudinal axis of the posts. Data were analyzed using the Student t test
(alpha=.05) and the coefficient of variance as the ratio of the standard
deviation to the mean. RESULTS: The mean pull-out retention strength was 185.7 +/
61.2 N for the prefabricated fiber posts and 98.9 +/-56.5 N for the individually
formed fiber posts (P=.026). CONCLUSIONS: The prefabricated fiber posts exhibited
significantly higher retention forces than the individually formed posts.
PMID- 29961615
TI - Effect of layered manufacturing techniques, alloy powders, and layer thickness on
mechanical properties of Co-Cr dental alloys.
AB - STATEMENT OF PROBLEM: The popularity of direct metal laser sintering (DMLS) and
melting (DMLM) has increased in dental practice. The layered manufacturing
device, the alloy powder, and the layer thickness may affect the mechanical
properties of layer-fabricated metals. PURPOSE: The purpose of this in vitro
study was to evaluate the mechanical, fractographic, and compositional properties
of metals fabricated by using different layered manufacturing techniques (DMLS
and DMLM), cobalt-chromium (Co-Cr) alloy powders, and layer thicknesses. MATERIAL
AND METHODS: A total of 90 dumbbell-shaped test specimens (n=15/group) were
fabricated by using either DMLS or DMLM. Powder alloys used were EOS Co-Cr SP-2
and Keramit NP-S, each with layer thicknesses of 20 and 30 MUm; their mechanical
properties were evaluated by using a test for tensile strength. Three-way ANOVA,
Student t test, and 1-way analysis of variance, followed by the Tukey honest
significant differences test were used for statistical analysis (alpha=.05). The
fracture surface was analyzed by using scanning electron microscopy, and energy
dispersive spectroscopy was used for compositional evaluation. RESULTS: Different
layered manufacturing equipment affected the mechanical properties of the final
objects, but the powder and layer thickness did not affect mechanical properties.
CONCLUSIONS: The powder and layer thickness did not affect mechanical properties
of the layered manufactured alloy, but different manufacturing methods did affect
the mechanical properties of the final product.
PMID- 29961616
TI - A custom positioning aid for an auricular prosthesis: A clinical report.
AB - This report describes the treatment of a 68-year-old man with basosquamous cell
carcinoma of the left auricular area. His oncologic treatment resulted in the
loss of his left ear and much of the left temporal bone. The loss of a
significant portion of the temporal bone precluded the use of extraoral implants.
Owing to the lack of anatomic landmarks after his surgical treatment, positioning
his auricular prosthesis proved challenging. The fabrication of his prosthesis
and a custom positioning aid are described.
PMID- 29961617
TI - The effect of extended glaze firing on the flexural fatigue strength of hard
machined ceramics.
AB - STATEMENT OF PROBLEM: It is unclear whether an extended glaze firing could
improve the long-term mechanical performance of densely sintered CAD-CAM
ceramics. PURPOSE: The purpose of this in vitro study was to analyze the effect
of an extended glaze firing on the flexural fatigue strength (FFS) of densely
sintered milled (hard-machined) leucite-based (LEU) and lithium disilicate-based
(DIS) ceramics. MATERIAL AND METHODS: Disks were machined from ceramic blocks and
divided into 6 groups (n=20) according to the material, LEU or DIS, and to the
applied glaze firing: manufacturer-recommended glaze (G group), extended glaze
(EG group), and control/no firing (C group). The surface roughness of the disks
was measured before and after firing by using a contact profilometer, and data
were compared by paired sample tests. Specimens were submitted to fatigue by
using the staircase test design in water (piston-on-3 balls; 500 000 cycles, 20
Hz, and sinusoidal loading). Mean (+/-SD) FFS values were then calculated and
analyzed by using 1-way analysis of variance and post hoc Tukey test (alpha=.05).
RESULTS: Surface roughness did not change after the firing (P>.05). The highest
FFS value in both ceramics was obtained after EG firing (LEU-EG=80.52 +/-6.3 MPa;
DIS-EG=147.25 +/-10.5 MPa), which was statistically superior to G firing (LEU
G=73 +/-6.8 MPa, P=.003; DIS-G=134.34 +/-15.6 MPa; P=.023) and C group (LEU
C=61.94 +/-6.3 MPa; P<.001; DIS-C=134.13 +/-17.3 MPa; P=.023). CONCLUSIONS: EG
firing optimized the biaxial flexural fatigue strength of hard-machined leucite
and lithium disilicate ceramics compared with conventional glaze firing.
PMID- 29961618
TI - The accuracy of virtual interocclusal registration during intraoral scanning.
AB - STATEMENT OF PROBLEM: Evidence on the accuracy and reproducibility of the virtual
interocclusal registration procedure and recommendations as to how to make a
virtual interocclusal record are lacking. PURPOSE: The purpose of this in vitro
study was to assess whether virtual interocclusal registration records made at
different locations around the arch affect the alignment of virtual casts, and to
assess whether quadrant and complete arch scans have different effects on cast
alignment when they are articulated with virtual interocclusal records. MATERIAL
AND METHODS: Three sites of close proximity (SCPs) and 3 sites of clearance (SCs)
were identified in each sextant of mounted zirconia master models. The SCPs and
SCs were confirmed by using shimstock foil and the transillumination of an
interocclusal impression. Complete-arch and quadrant scans of the master models
were made with an intraoral scanner and registered with different virtual
interocclusal registration records. The SCPs and SCs indicated by the scanner's
software and by independent software were compared according to the sensitivity,
specificity, and predictive values of each method. RESULTS: Changed locations of
SCPs were found depending on the location of the virtual interocclusal
registration record. The intraoral scanner's software contacts had a higher
sensitivity of 92.86% and a negative predictive value of 84.21% than the contacts
revealed by the independent software that exhibited a sensitivity of 69.05% and a
negative predictive value of 70.45%. However, the intraoral scanner software had
a lower specificity of 41.03% and a positive predictive value of 62.90% compared
with the independent software, which exhibited a specificity of 79.49% and a
positive predictive value of 78.38%. The quadrant scans had a higher sensitivity
than did the complete-arch scans. CONCLUSIONS: Different occlusal contacts are
obtained from interocclusal registration scans in different segments of the
dental arch. The difference is more obvious in complete-arch scans, where a
tilting effect toward the site of the interocclusal registration scan was
observed. Occlusal contacts obtained from interocclusal registration scans for
quadrant scans had a higher sensitivity than did those for complete-arch scans.
PMID- 29961619
TI - Combination of digital photographs for the identification of the screw-access
hole of cement-retained implant restorations.
PMID- 29961620
TI - Use of finite element analysis for the assessment of biomechanical factors
related to pain sensation beneath complete dentures during mastication.
AB - STATEMENT OF PROBLEM: The pain commonly suffered by denture wearers during
mastication is not documented in the objective biomechanical criteria for the
pressure pain threshold. PURPOSE: The purpose of this finite element analysis
study was to determine whether the pressures developed beneath a removable
mandibular complete denture during mastication would exceed the average pressure
pain threshold in patients for whom the denture foundation had an acceptable load
bearing capacity. MATERIAL AND METHODS: A patient with an acceptable load-bearing
denture foundation was modeled with finite element analysis. The denture/mucosa
interface was modeled as a sliding or detaching interface. A convex mandibular
residual ridge, resilient mucosa, and denture were modeled in computer-aided
design (CAD) software using curves and cross sections. A unilateral vertical
occlusal load of 100 N was assumed only for model verification, and an oblique
mastication load of 141 N was assumed for simulated mastication with balanced
articulation. The nonworking-side occlusal contact was simulated in 2 situations:
prompt nonworking-side occlusal contact and delayed nonworking-side occlusal
contact by setting an initial distance of 0.1 mm or 1 mm between the denture and
a flat solid above the nonworking side. RESULTS: The denture was held to the
mucosa under vertical force and a maximum pressure of 203 kPa. The denture was
tilted under an oblique mastication load and achieved stability through
nonworking-side occlusal contact. This means that the denture was supported not
only by the denture foundation but also by the nonworking-side occlusal contact
and had a downwardly directed stabilizing reaction force. The denture was weakly
supported on the delayed nonworking-side occlusal contact compared with the
prompt nonworking-side occlusal contact and weakly supported on the denture
foundation. In delayed nonworking-side occlusal contact, the pressure beneath the
denture was 783 kPa (>pressure pain threshold) compared with 484 kPa (.05). However, the implant orientation of group OBJ was significantly
different from the orientation of groups GYP and FORM (P<.05). The actual
clinical relevance of these printing system discrepancies is yet to be determined
because the level of clinical acceptable discrepancy in the x, y, and z vectors
is still undefined. CONCLUSIONS: This study showed statistically significant
differences in accuracy among the implant analog cast fabrication systems;
however; the level of clinical acceptable discrepancy is still undefined.
Although further research is needed, this study supports the conclusion that the
Polyjet industrial printing system was more accurate than the conventional
implant analog gypsum cast.
PMID- 29961628
TI - Comparison of marginal fit between CAD-CAM and hot-press lithium disilicate
crowns.
AB - STATEMENT OF PROBLEM: Hot-pressing and computer-aided design and computer-aided
manufacturing (CAD-CAM) are major techniques for the fabrication of lithium
disilicate crowns. They exhibit different accuracies regarding marginal fit, an
important factor in restoration survival. However, studies comparing the marginal
fit of different fabrication methods are lacking. PURPOSE: The purpose of this in
vitro study was to compare the marginal discrepancy (MD) and absolute marginal
discrepancy (AMD) of lithium disilicate crowns produced by the hot-press and CAD
CAM techniques. MATERIAL AND METHODS: Thirty (30) typodont teeth were divided
into 2 groups. Fifteen teeth were scanned with the CEREC Omnicam intraoral
scanner, and crowns were fabricated with the CEREC MC XL chairside CAD-CAM
milling unit from IPS e.max CAD blocks. Fifteen typodont teeth were sent to a
dental laboratory, and lithium disilicate crowns were fabricated from IPS e.max
press ingots using the hot-press technique. The 30 crowns were cemented and then
sectioned with a precision saw. The MD and AMD were measured for each crown with
a light microscope. One-way ANOVA was conducted to analyze significant
differences in crown marginal fit between the fabrication systems (alpha=.05).
RESULTS: For the CAD-CAM technique, the mean values of the AMD measurements were
115 MUm, and for the hot-press technique, 130 MUm. The MD measurements were 87
MUm for the CAD-CAM technique and 90 MUm for the hot-press technique. One-way
ANOVA revealed no significant differences between the fabrication methods
regarding marginal fit (P>05). CONCLUSIONS: No significant differences were found
between the fabrication methods tested. Both the CAD-CAM and hot-press techniques
for producing monolithic lithium disilicate crowns produced MD values of less
than 120 MUm, within the clinically acceptable range.
PMID- 29961629
TI - Load-bearing capacity of simulated Locator-retained overdenture system.
AB - STATEMENT OF PROBLEM: Acrylic resin overdenture bases usually fracture because of
stress concentrations at the area of the abutments. PURPOSE: The purpose of this
study was to evaluate the reinforcing effect of bidirectional woven electrical
glass (E-glass) fiber weaves with a different number of layers and different
locations on the load-bearing capacity of simulated Locator-retained overdenture
specimens. MATERIAL AND METHODS: Test specimens with a centrally located metal
housing for a Locator stud attachment were fabricated from autopolymerizing
acrylic resin (polymethylmethacrylate based) and reinforced with bidirectional
woven E-glass fiber layers. The control group specimens were fabricated without
fiber reinforcement. The 2L group had 2 layers of E-glass fiber weaves and was
divided according to the fiber location within the specimens as follows: 2L-A
subgroup with 2 fiber layers above the metal housing; 2L-N subgroup with 2 fiber
layers adjacent to the housing; and 2L-A+2L-N subgroup with 2 fiber layers above
and 2 fiber layers adjacent to the housing. The 4L group had 4 layers of E-glass
fiber weaves and was divided according to the fiber location as follows: 4L-A
subgroup with 4 fiber layers above the housing; 4L-N subgroup with 4 fiber layers
adjacent to the housing; and 4L-A+4L-N subgroup with 4 fiber layers above and 4
fiber layers adjacent to the housing. Dry specimens were submitted to a 3-point
static loading test, and the mean flexural strength, flexural modulus, and strain
values were analyzed with 1-way ANOVA and Tukey post hoc tests (alpha=.05). Two
way ANOVA was conducted to detect the influence of the number and location of the
reinforcing layers (alpha=.05). RESULTS: The results revealed a significant
difference (P<.001) in flexural strength values between the control group (92.4
+/-14 MPa) and the 2 subgroups, 4L-A (116 +/-7.3 MPa) and 4L-A+4L-N (117.1 +/-6
MPa), with a significant effect only from the number of the reinforcing layers
(P<.001) and not the location (P=.153). No significant differences were found
with flexural modulus (P=.195) and strain values (P=.174) among the tested
groups. CONCLUSIONS: The load-bearing capacity of a Locator-retained overdenture
can be significantly increased by placing 4 layers of bidirectional woven E-glass
fiber weaves either only above the metal housing or in both locations above and
adjacent to the metal.
PMID- 29961630
TI - Digital workflow to rehabilitate worn dentition on a non-hinge simulated patient.
AB - This report describes the complete mouth rehabilitation of worn dentition by
using a digital workflow on a non-hinge simulated patient. A dentiform was used
to simulate a patient with loss of occlusal vertical dimension. Physical
diagnostic waxing along with a digital workflow was then used to re-establish the
occlusal vertical dimension at the interim and definitive restoration stages.
PMID- 29961631
TI - Replacement of maxillary incisor crowns over discolored substrates in a single
visit with a CAD-CAM system and lithium silicate ceramic.
AB - Discolored substrates constitute a challenge to the esthetics of the definitive
restoration. Because of technique sensitivity, the generally prolonged treatment
time is a drawback to both the patient and the dentist. The technique described
presents the replacement of ceramic maxillary incisors crowns over discolored
substrates in a single visit by using a milling machine. Translucent blocks of a
lithium silicate ceramic reinforced with zirconium dioxide particles were used.
Intraoral scans of the trial restorations and of the tooth preparations were
performed. The crown parameters were defined in the software. Ceramic blocks were
milled in the presintered phase and characterized. The crowns were cemented at
the end of the appointment with excellent esthetics.
PMID- 29961632
TI - Should the restoration of adjacent implants be splinted or nonsplinted? A
systematic review and meta-analysis.
AB - STATEMENT OF PROBLEM: The decision to splint or to restore independently
generally occurs during the planning stage, when the advantages and disadvantages
of each clinical situation are considered based on the proposed treatment.
However, clinical evidence to help clinicians make this decision is lacking.
PURPOSE: The purpose of this systematic review and meta-analysis was to assess
the marginal bone loss, implant survival rate, and prosthetic complications of
splinted and nonsplinted implant restorations. MATERIAL AND METHODS: This study
was designed according to the Cochrane criteria for elaborating a systematic
review and meta-analysis and adopted the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) statement. Also, this review was registered at
the International Prospective Register of Systematic Reviews (PROSPERO)
(CRD42017080162). An electronic search in the PubMed/MEDLINE, Cochrane Library,
and Scopus databases was conducted up to November 2017. A specific clinical
question was structured according to the population, intervention, comparison,
outcome (PICO) approach. The addressed focused question was "Should the
restoration of adjacent implants be splinted or nonsplinted?" The meta-analysis
was based on the Mantel-Haenszel and inverse variance methods to assess the
marginal bone loss, implant survival, and prosthetic complications of splinted
and nonsplinted implant restorations. RESULTS: Nineteen studies were selected for
qualitative and quantitative analyses. A total of 4215 implants were placed in
2185 patients (splinted, 2768; nonsplinted, 1447); the mean follow-up was 87.8
months (range=12-264 months). Quantitative analysis found no significant
differences between splinted and nonsplinted restorations for marginal bone loss.
The assessed studies reported that 75 implants failed (3.4%), of which 24 were
splinted (99.1% of survival rate) and 51 were nonsplinted (96.5% of survival
rate). Quantitative analysis of all studies showed statistically significant
higher survival rates for splinted restorations than for nonsplinted
restorations. Ceramic chipping, screw loosening, abutment screw breakage, and
soft tissue inflammation were reported in the selected studies. The quantitative
analysis found no statistically significant difference in the prosthetic
complications of splinted and nonsplinted restorations. CONCLUSIONS: Within the
limitations of this systematic review and meta-analysis, it was concluded that
there was no difference in the marginal bone loss and prosthetic complications of
splinted and nonsplinted implant restorations; this is especially true for
restorations in the posterior region. However, splinted restorations were
associated with decreased implant failure.
PMID- 29961633
TI - Osteogenesis ability of CAD-CAM biodegradable polylactic acid scaffolds for
reconstruction of jaw defects.
AB - STATEMENT OF PROBLEM: Reconstruction of alveolar bony defects is difficult using
grafting materials in a powder form. A biodegradable scaffold material might
simplify the procedure. PURPOSE: The purpose of this in vivo study was to
evaluate osteogenesis ability of a biodegradable CAD-CAM-fabricated polylactic
acid (PLA) scaffold enriched with calcium phosphate salts including
hydroxyapatite (HA) and beta tricalcium phosphate (beta-TCP) used to reconstruct
mandibular defects in a dog model. MATERIAL AND METHODS: Surgical defects were
made bilaterally in the mandible of male beagle dogs. Computerized tomography
images were obtained for determination of the 3-dimensional shape of the defects
after 3 months of healing. Porous PLA scaffolds were fabricated by milling custom
made CAD-CAM blocks into the desired shape. After milling, half of the scaffolds
were prepared by filling the pores of the scaffolds by a mixture of HA and beta
TCP. Scaffolds were inserted in the mandibular defects bilaterally. After a
healing time of 8 weeks, the bone-scaffold interface was analyzed
histomorphometrically to detect the amount of new bone formation. Stained
histological sections were examined using a computer software and depth of new
bone formation was assessed (n=14, alpha=.05). RESULTS: Histomorphometric
analysis revealed that enriched scaffolds with calcium phosphates had
significantly (t=4.4, P<.001) higher amounts of new bone formation (1.3 +/-0.33
mm) compared with the controls (0.7 +/-0.39 mm). Average new bone growth in
enriched scaffolds was 1.3 mm while almost half this value was observed in
uncoated scaffolds, 0.7 mm. CONCLUSIONS: Within the limitations of this animal
study, HA and beta-TCP enhanced osteogenesis ability of CAD-CAM-fabricated PLA
scaffolds.
PMID- 29961634
TI - Immediate placement of dental implants into infected versus noninfected sites in
the esthetic zone: A systematic review and meta-analysis.
AB - STATEMENT OF PROBLEM: Immediate implantation has been established to shorten
waiting time before definitive restoration, offering the ability to deliver a
predictable esthetic and functional outcome for patients. However, this approach
remains controversial for a tooth with a periodontal or periapical lesion.
PURPOSE: The purpose of this systematic review was to analyze the treatment
outcomes of immediate implant placement into extraction sockets with or without
infection of periodontal or periapical origin in the esthetic zone and to provide
treatment protocols based on current studies. MATERIAL AND METHODS: An electronic
search was performed in PubMed, ISI Web of Knowledge, and the Cochrane Library
between January 2009 and October 2017. A subsequent manual search included all
clinical studies published in the English language and excluded any reviews or
animal studies. An article quality assessment scale, Newcastle-Ottawa Scale
(NOS), was used to evaluate the quality of studies enrolled. The implant survival
rate was expressed as risk ratio, whereas bone level changes and gingiva level
changes were expressed as mean differences in millimeters with 95% confidence
intervals. The meta-analysis was conducted by using commercial software. RESULTS:
The search initially found 1171 references. The manual search of the reference
lists of identified articles yielded additional papers. Altogether, 9 studies
were identified within the selection criteria, with NOS scores between 5 and 8.
Compared with the healthy sites, immediate implant placement in infected sites in
the esthetic zone showed similar survival rates (97.6% vs. 98.4%, respectively;
risk ratio [RR], 0.99; 95% confidence interval [CI], 0.97 to 1.00; P=.138). No
statistically significant differences were found in bone level changes (mean
difference [MD], 0.03; 95%CI, -0.09 to 0.14; P=.667) or in gingiva level changes
(MD, -0.06; 95% CI, -0.13 to 0.01; P=.070) between the 2 groups. CONCLUSIONS:
Meta-analysis showed that immediate implant placement into infected sites and
noninfected sites in esthetic zone had similar survival rates, bone level
changes, and gingiva level changes.
PMID- 29961635
TI - Patient-centred care for multimorbidity: an end in itself?
PMID- 29961636
TI - Reducing NCDs globally: the under-recognised role of environmental risk factors.
PMID- 29961637
TI - Discontinuing tumour necrosis factor inhibitors in non-radiographic axial
spondyloarthritis.
PMID- 29961638
TI - Management of multimorbidity using a patient-centred care model: a pragmatic
cluster-randomised trial of the 3D approach.
AB - BACKGROUND: The management of people with multiple chronic conditions challenges
health-care systems designed around single conditions. There is international
consensus that care for multimorbidity should be patient-centred, focus on
quality of life, and promote self-management towards agreed goals. However, there
is little evidence about the effectiveness of this approach. Our hypothesis was
that the patient-centred, so-called 3D approach (based on dimensions of health,
depression, and drugs) for patients with multimorbidity would improve their
health-related quality of life, which is the ultimate aim of the 3D intervention.
METHODS: We did this pragmatic cluster-randomised trial in general practices in
England and Scotland. Practices were randomly allocated to continue usual care
(17 practices) or to provide 6-monthly comprehensive 3D reviews, incorporating
patient-centred strategies that reflected international consensus on best care
(16 practices). Randomisation was computer-generated, stratified by area, and
minimised by practice deprivation and list size. Adults with three or more
chronic conditions were recruited. The primary outcome was quality of life
(assessed with EQ-5D-5L) after 15 months' follow-up. Participants were not masked
to group assignment, but analysis of outcomes was blinded. We analysed the
primary outcome in the intention-to-treat population, with missing data being
multiply imputed. This trial is registered as an International Standard
Randomised Controlled Trial, number ISRCTN06180958. FINDINGS: Between May 20,
2015, and Dec 31, 2015, we recruited 1546 patients from 33 practices and randomly
assigned them to receive the intervention (n=797) or usual care (n=749). In our
intention-to-treat analysis, there was no difference between trial groups in the
primary outcome of quality of life (adjusted difference in mean EQ-5D-5L 0.00,
95% CI -0.02 to 0.02; p=0.93). 78 patients died, and the deaths were not
considered as related to the intervention. INTERPRETATION: To our knowledge, this
trial is the largest investigation of the international consensus about optimal
management of multimorbidity. The 3D intervention did not improve patients'
quality of life. FUNDING: National Institute for Health Research.
PMID- 29961640
TI - Efficacy and safety of continuing versus withdrawing adalimumab therapy in
maintaining remission in patients with non-radiographic axial spondyloarthritis
(ABILITY-3): a multicentre, randomised, double-blind study.
AB - BACKGROUND: Success of treatment withdrawal in patients with non-radiographic
axial spondyloarthritis who are in remission remains unknown. The ABILITY-3 study
explored the ability to withdraw adalimumab treatment in patients with non
radiographic axial spondyloarthritis who achieved sustained clinical remission
after open-label treatment with adalimumab. METHODS: ABILITY-3 was a multicentre,
two-period study done in 107 sites in 20 countries. We enrolled adult patients
(>=18 years) diagnosed with non-radiographic axial spondyloarthritis, fulfilling
Assessment of SpondyloArthritis international Society classification criteria but
not the modified New York radiologic criterion, who had objective evidence of
active inflammation, active disease, and inadequate response to at least two non
steroidal anti-inflammatory drugs. Patients who achieved Ankylosing Spondylitis
Disease Activity Score (ASDAS) inactive disease (<1.3) with open-label adalimumab
(40 mg subcutaneously every other week for 28 weeks) at weeks 16, 20, 24, and 28
were randomly assigned (1:1) using an interactive voice or web response system to
40-week, double-blind treatment with adalimumab (continuation) or placebo
(withdrawal). The primary efficacy endpoint was the proportion of patients who
did not experience a flare (defined as ASDAS >=2.1 at two consecutive visits)
during the double-blind period. Patients who flared were rescued with open-label
adalimumab. This study is registered with ClinicalTrials.gov, number NCT01808118.
FINDINGS: Between June 27, 2013, and October 22, 2015, 673 patients were enrolled
to the study. The trial completed on April 14, 2017. Of 673 enrolled patients,
305 (45%) achieved sustained remission and were randomly assigned to double-blind
treatment (152 patients to adalimumab and 153 to placebo). A greater proportion
of patients continuing adalimumab than those receiving placebo did not experience
a flare (107 [70%] of 152 patients vs 72 [47%] of 153 patients; p<0.0001) up to
and including week 68. Among 673 patients receiving adalimumab at any time, 516
(77%) patients reported an adverse event and 28 (4%) experienced a serious
adverse event. The most common adverse events in both the adalimumab and placebo
groups were nasopharyngitis (25 [16%] vs 20 [13%]), upper respiratory tract
infection (20 [13%] vs 12 [8%]), and worsening of axial spondyloarthritis (ten
[7%] vs 21 [14%]). INTERPRETATION: In patients with active non-radiographic axial
spondyloarthritis who achieved sustained remission with adalimumab, continued
therapy was associated with significantly fewer patients flaring than was
treatment withdrawal. FUNDING: AbbVie.
PMID- 29961642
TI - Oxygen Treatment for Immature Infants beyond the Delivery Room: Lessons from
Randomized Studies.
PMID- 29961641
TI - The how: a message for the UN high-level meeting on NCDs.
PMID- 29961639
TI - On the road to universal health care in Indonesia, 1990-2016: a systematic
analysis for the Global Burden of Disease Study 2016.
AB - BACKGROUND: As Indonesia moves to provide health coverage for all citizens,
understanding patterns of morbidity and mortality is important to allocate
resources and address inequality. The Global Burden of Disease 2016 study (GBD
2016) estimates sources of early death and disability, which can inform policies
to improve health care. METHODS: We used GBD 2016 results for cause-specific
deaths, years of life lost, years lived with disability, disability-adjusted life
years (DALYs), life expectancy at birth, healthy life expectancy, and risk
factors for 333 causes in Indonesia and in seven comparator countries. Estimates
were produced by location, year, age, and sex using methods outlined in GBD 2016.
Using the Socio-demographic Index, we generated expected values for each metric
and compared these against observed results. FINDINGS: In Indonesia between 1990
and 2016, life expectancy increased by 8.0 years (95% uncertainty interval [UI]
7.3-8.8) to 71.7 years (71.0-72.3): the increase was 7.4 years (6.4-8.6) for
males and 8.7 years (7.8-9.5) for females. Total DALYs due to communicable,
maternal, neonatal, and nutritional causes decreased by 58.6% (95% UI 55.6-61.6),
from 43.8 million (95% UI 41.4-46.5) to 18.1 million (16.8-19.6), whereas total
DALYs from non-communicable diseases rose. DALYs due to injuries decreased, both
in crude rates and in age-standardised rates. The three leading causes of DALYs
in 2016 were ischaemic heart disease, cerebrovascular disease, and diabetes.
Dietary risks were a leading contributor to the DALY burden, accounting for 13.6%
(11.8-15.4) of DALYs in 2016. INTERPRETATION: Over the past 27 years, health
across many indicators has improved in Indonesia. Improvements are partly offset
by rising deaths and a growing burden of non-communicable diseases. To maintain
and increase health gains, further work is needed to identify successful
interventions and improve health equity. FUNDING: The Bill & Melinda Gates
Foundation.
PMID- 29961643
TI - The correct use of noninferiority trials.
PMID- 29961644
TI - Patterns of Dietary Supplement Use in Children with Down Syndrome.
AB - OBJECTIVE: To determine the frequency of dietary supplement use for children with
Down syndrome, and to obtain additional descriptive data regarding the age of
initial treatment, cost, perceived benefits, and disclosure of use to the
pediatrician. STUDY DESIGN: An anonymous questionnaire in English and Spanish was
created for parents of children under age 18 years with Down syndrome. Surveys
were completed in our clinic, or accessed on a number of Down syndrome-related
websites. RESULTS: A total of 1167 responses were completed and analyzed. Forty
nine percent of responders currently/previously gave their child supplement(s).
The average child received 3 supplements (ranging from 1-18). Although Nutrivene,
curcumin, and green tea extract were most common, over 150 different products
were reported. Supplementation began most often in infancy, generally between age
4 and 6 months. Average cost was $90.53/month. Overall, 87% of users noted
improvement, mainly in speech, immunity, and attention; 17% reported side
effects, predominantly gastrointestinal disturbance. Lack of improvement and cost
were the main reasons for discontinuation. Most parents learned of supplements
through a parent group or friend. In almost 20%, the pediatrician was unaware of
the supplement use. CONCLUSIONS: Almost one-half of parents surveyed administer
or have administered supplement(s) to their children with Down syndrome. Many of
the supplements have concerning ingredient profiles and are given to children too
young to articulate potential ill effects. Providers need to be aware of these
products and question families about their use.
PMID- 29961645
TI - Reply.
PMID- 29961646
TI - Skin-to-skin care cannot be blamed for increase in suffocation deaths.
PMID- 29961647
TI - Use of a Pediatric Syncope Unit Improves Diagnosis and Lowers Costs: A Hospital
Based Experience.
AB - OBJECTIVES: To assess the effect of a dedicated pediatric syncope unit on the
diagnostic and therapeutic management of children with suspected syncope. We also
evaluated the effectiveness of the pediatric syncope unit model in decreasing
unnecessary tests and hospitalizations, minimizing social costs, and improving
diagnostic yield. STUDY DESIGN: This single-center cohort observational,
prospective study enrolled 2278 consecutive children referred to Bambino Gesu
Children's Hospital from 2012 to 2017. Characteristics of the study population,
number and type of admission examinations, and diagnostic findings before the
pediatric syncope unit was implemented (2012-2013) and after the pediatric
syncope unit was implemented (2014-2015 and 2016-2017) were compared. RESULTS:
The proportion of undefined syncope, number of unnecessary diagnostic tests
performed, and number of hospital stay days decreased significantly (P < .0001),
with an overall decrease in costs. A multivariable logistic regression analysis,
adjusted for confounding variables (age, sex, number of diagnostic tests), the
period after pediatric syncope unit (2016-2017) resulted as the best independent
predictor of effectiveness for a defined diagnosis of syncope (P < .0001).
CONCLUSIONS: Pediatric syncope unit organization with fast-tracking access more
appropriate diagnostic tests is effective in terms of accuracy of diagnostic
yield and reduction of costs.
PMID- 29961648
TI - Variance in interpretation of plain radiographs for the assessment of third
molars for coronectomy: our solution.
PMID- 29961649
TI - Serum vitamin D levels correlate with the presence and histological grading of
colorectal adenomas in peri and postmenopausal women.
AB - BACKGROUND & AIMS: Vitamin D is known to modulate immune function and
proliferation. Higher vitamin D [25(OH)D3] serum levels have been reported to
have protective effects on adenoma detection and colorectal cancer (CRC)
development and survival. METHODS: This retrospective cohort study included 315
peri and post-menopausal women submitted to opportunistic colorectal and
osteoporosis screening at the gynaecology outpatient clinic of a tertiary medical
centre between 2004 and 2015. Colonoscopy findings were correlated with 25(OH)D3
and PTH serum levels, and subsequently adjusted in a multivariate logistic
regression model. Confounding factors included demographic and colorectal risk
factors, pharmacological therapies and bone densitometry metrics. RESULTS: A
total of 77 lesions were identified in 66 patients. Vitamin D insufficiency (<30
ng/mL) and deficiency (<20 ng/mL) were identified in 79.4% and 35.2% of patients,
respectively. In univariate analysis, lower levels of 25(OH)D3 were associated
with polyp, adenoma and advanced adenoma detection. After adjusting for
confounders, an association with polyps could not be observed, but a trend
towards a negative correlation with adenoma detection was found (adjusted OR:
0.96; 95% CI 0.92-1.00; p = 0.083). Regarding advanced adenoma detection,
25(OH)D3 (adjusted OR: 0.86; 95% CI 0.77-0.97; p = 0.013) proved to be an
independent predictive factor. No association was found between 25(OH)D3 levels
and lesion detection site. CONCLUSION: The association of 25(OH)D3 serum levels
with colorectal lesions seems to be restricted to adenomatous lesions and is
influenced by histological grading. Vitamin D may be a valuable biomarker for
optimization of risk stratification in group-specific CRC screening protocols.
PMID- 29961650
TI - Quantification of inorganic anions and organic acids in apple and orange juices
using novel covalently-bonded hyperbranched anion exchanger with improved
selectivity.
AB - Chromatographic analysis of orange and apple juices is provided using novel
covalently-bonded poly(styrene-divinylbenzene)-based (PS-DVB) hyperbranched anion
exchanger for suppressed ion chromatography (IC) with improved selectivity toward
inorganic anions and organic acids. The obtained stationary phase provides
baseline resolution of weakly retained organic acids such as glycolate, acetate,
lactate, and formate, which are not separated to baseline with modern
commercially available anion exchangers. The proposed method is validated with
respect to linearity, recovery, limits of detection, and intra-day and inter-day
precision.
PMID- 29961651
TI - Challenging pharmaceutical analyses by gas chromatography with vacuum ultraviolet
detection.
AB - Vacuum ultraviolet (VUV) detector for gas chromatography (GC) provides
qualitative spectral information from 125 nm to 240 nm. In this article, this
information was applied to facilitate the development of a GC method for
challenging pharmaceutical applications. Seven organic solvents were screened for
trace level water content using VUV detection at 168 nm, and the results were
used to identify n-hexane as a suitable diluent for 4-ethoxy-1,1,1-trifluoro-3
buten-2-one (ETFBO), a water reactive compound. Selective detection of compounds
of interest was demonstrated by varying detection wavelengths. All compounds were
detected at 145 nm except for one unknown impurity, which co-eluted with n-hexane
solvent. This impurity was detected at 225 nm, where n-hexane has no absorbance.
In addition, the VUV spectra were used to: 1) accurately track peaks during early
method development; 2) detect co-eluting peaks; 3) match peak identity in a
sample vs. a standard; and 4) assess peak purity. With the universal
detectability, qualitative spectral information and ease of use, VUV will become
a versatile tool for GC for both method development and routine analysis.
PMID- 29961652
TI - Enantioseparation of fluorinated 3-arylthio-4,4'-bipyridines: Insights into
chalcogen and pi-hole bonds in high-performance liquid chromatography.
AB - A chalcogen bond (ChB) is a sigma-hole-based noncovalent interaction between a
Lewis base and an electrophilic element of Group VI (O, S, Se, Te), which behaves
as a Lewis acid. Recently, we demonstrated that halogen bond, the more familiar
sigma-hole-based interaction, is able to promote the enantioseparation of chiral
compounds in HPLC environment. On this basis, an investigation to detect ChBs,
functioning as stereoselective secondary interactions for HPLC
enantioseparations, was started off and the results of this study are described
herein. Our investigation also focused on the impact of the perfluorinated
aromatic ring as a pi-hole donor recognition site. For these purposes, seven
atropisomeric fluorinated 3-arylthio-4,4'-bipyridines were designed, synthesized
and used as potential ChB donors (ChBDs) with two cellulose-based chiral
stationary phases (CSPs) containing carbonyl groups as ChB acceptors (ChBAs). In
addition, one and two analogues lacking fluorine and sulphur, respectively, were
prepared as terms of comparison. The design of the test analytes was
computationally guided. In this regard, electrostatic potentials (EPs) associated
with sigma- and pi-holes were computed and the atomic contributions to the
sulphur EP maxima were derived using a molecular space partitioning in terms of
Bader's atomic basins. This procedure is akin to the Bader-Gatti electron density
source function (SF) decomposition, yet suitably extended to the EP field. For
five 3-substituted-4,4'-bipyridines, thermodynamic parameters were derived from
van't Hoff plots. Finally, the use of molecular dynamic (MD) simulation to model
ChB in cellulose-analyte complexes was explored. Evidences that sigma-hole and pi
hole interactions can jointly drive HPLC enantioseparations through recognition
sites generated by electronic charge depletion emerged from both experimental
results and theoretical data.
PMID- 29961653
TI - Depression and Anxiety in Patients With Pulmonary Hypertension: The Role of Life
Satisfaction and Optimism.
AB - BACKGROUND: Pulmonary hypertension is a highly disabling condition characterized
by a progressive increase in pulmonary arterial pressure. Even though pulmonary
hypertension may cause great emotional distress, research examining the
determinants of patients' emotional well-being has been scarce and has mostly
focused on the role of disease-related factors. OBJECTIVES: This study examined
whether patients' emotional well-being may be effected by their life
circumstances. METHODS: Sixty-four patients with pulmonary hypertension completed
measures of symptoms of pulmonary hypertension, functional disability, depression
and anxiety symptoms, life satisfaction, optimism, and quality of life (QoL).
RESULTS: Clinically-significant symptoms of depression and anxiety were only
accurately predicted in 50.5% and 56.5% of patients, respectively, based on
disease severity alone. However, the addition of life satisfaction and optimism
to the models improved the prediction of depressive and anxiety symptomatology.
Further, symptoms of anxiety were a significant predictor of QoL, above and
beyond disease severity. CONCLUSIONS: Patients with considerably different levels
of disease severity may develop clinically-significant depressive and anxiety
symptomatology. This suggests that there is not a perfect correspondence between
the level of disease severity and the repercussions thereof across patients.
Accordingly, these results suggest that emotional well-being may be better
explained by taking into consideration patients' life circumstances, as these may
modulate the repercussions of having pulmonary hypertension. The results also
showed that anxiety symptoms constituted an extra burden to patients' QoL. The
higher prevalence in this sample of clinically-significant symptoms of anxiety,
compared to that of depression, suggest that feelings of fear and uncertainty may
require special attention among patients with pulmonary hypertension.
PMID- 29961654
TI - Stereotactic radiotherapy in three weekly fractions for the management of
vestibular schwannomas.
AB - PURPOSE: This study evaluates the rates of tumor control, hearing preservation
and cranial nerve toxicity with the use of CyberKnife stereotactic radiotherapy
consisting of 2100 cGy to the 80% isodose line delivered in three weekly
fractions to treat vestibular schwannomas. MATERIALS AND METHODS: Retrospective
chart review of vestibular schwannoma patients treated with CyberKnife
stereotactic radiotherapy or undergoing watchful waiting between 2006 and 2017
was performed. For inclusion, patients receiving CyberKnife stereotactic
radiotherapy must have had pretreatment magnetic resonance imaging and
audiography, and 2 follow-up magnetic resonance imaging and audiograms. Watchful
waiting patients must have had a minimum of 2 magnetic resonance imaging and 2
audiograms. RESULTS: Forty patients met inclusion criteria. Twenty-two underwent
CyberKnife stereotactic radiotherapy. Eighteen remain in watchful waiting. Crude
tumor control was 86.4% at mean radiographic follow-up of 52.3 months. Kaplan
Meier progression-free survival was 76.9% at 5 years. Kaplan-Meier survival from
radiographic growth was 61.5% at 5 years. Kaplan-Meier hearing preservation was
17.5% at 5 years. All patients undergoing watchful waiting presenting with
serviceable hearing maintained serviceable hearing. Serviceable hearing among
CyberKnife stereotactic radiotherapy patients was 42.9% prior to treatment and
14.2% through mean follow-up of 53.7 months. One patient experienced trigeminal
nerve toxicity 45 months after SRT. 95.5% of CyberKnife stereotactic radiotherapy
patients were complication-free. CONCLUSIONS: Our fractionation regimen provides
tumor control consistent with current literature. Hearing outcomes, however,
should be discussed with patients prior to CyberKnife stereotactic radiotherapy.
PMID- 29961655
TI - Utility of narrow band imaging in the diagnosis of middle turbinate head edema.
AB - PURPOSE: Middle turbinate head edema has recently been found to have high
specificity for diagnosis of inhalant allergy. However, subtle mucosal edema can
be difficult to appreciate under white light endoscopy. Narrow band imaging (NBI)
has the potential to demonstrate edema by identifying reduced mucosal vascularity
and improve sensitivity for the detection of mucosal edema. Narrow band imaging
was assessed to determine its utility in objectifying mucosal edema. MEATERIALS
AND METHODS: A cross-sectional diagnostic study was performed on patients with
edematous mucosa of the middle turbinate head. Under traditional white light
endoscopy, areas of edematous mucosa were identified. Using NBI, these areas were
compared to areas of normal mucosa on the middle turbinate head. NBI images of
these same areas were then converted to grey scale and a vascularity index was
created by pixel analysis and brightness in Fiji Image J software (Wisconsin,
US). RESULTS: Thirty-three middle turbinates were assessed (age 42.4 +/- 12.5,
42.4% female). NBI discriminated between areas identified under white light
endoscopy as edematous and normal (158.2 +/- 48.4 v 96.9 +/- 32.7 p < 0.01).
Receiver operating curve (ROC) analysis suggested a threshold of 115 brightness
units to define endoscopically visible edematous mucosa with sensitivity 70% and
specificity 79% (ROC AUC, p = 0.85). CONCLUSIONS: NBI can differentiate edematous
from normal mucosa. The potential for an objective measure of mucosal edema may
assist research efforts and may provide a more sensitive tool for subtle mucosal
inflammatory changes.
PMID- 29961656
TI - A case report of cyanotic nephropathy.
PMID- 29961657
TI - WIC Participation and Blood Lead Levels among Children 1-5 Years: 2007-2014.
AB - BACKGROUND: The CDC recommends a targeted strategy for childhood blood lead
screening based on participation in federal programs, such as Medicaid and the
Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).
Yet, there is scarcity of data on blood lead levels (BLLs) among WIC
participants. OBJECTIVE: Our objective was to investigate whether children
participating in WIC and not enrolled in Medicaid, who have not been targeted in
the historical Medicaid-focused screening strategy, have higher BLLs than
children in neither of these programs. METHODS: The analysis included 3,180
children 1-5 y of age in the National Health and Nutrition Examination Surveys
conducted in 2007-2014. Log-binomial regression, which allows direct estimation
of prevalence ratios, was used to examine associations between WIC participation
(in conjunction with Medicaid enrollment) and having BLLs >=5 MUg/dL with
adjustment for age (1-2 vs. 3-5 y). RESULTS: The percentage of children
participating in "WIC only," "Medicaid only," "both WIC and Medicaid," and
"neither" were 18.9%, 10.8%, 25.4%, and 44.9%, respectively. "WIC only,"
"Medicaid only," and "both WIC and Medicaid" children were more likely to have
BLLs >=5 MUg/dL than children who were not enrolled in either program, with
adjusted prevalence ratios of 3.29 [95% confidence interval (CI): 1.19, 9.09],
4.56 (95% CI: 2.18, 9.55), and 2.58 (95% CI: 1.18, 5.63). CONCLUSIONS: Children
participating in WIC but not Medicaid were more likely to have BLLs >=5 MUg/dL
than children who were not enrolled in either program. These findings may inform
public health recommendations and clinical practice
guidelines.https://doi.org/10.1289/EHP2384
PMID- 29961658
TI - The Health of Our Health Care System.
PMID- 29961659
TI - Clinical Pearls.
PMID- 29961660
TI - Ensuring Breathing Comfort at the End of Life: The Integral Role of the Critical
Care Nurse.
AB - This article describes the author's program of clinical research focused on
assessment and treatment of respiratory distress among critically ill patients at
the end of life. Dyspnea is a subjective experience of breathing discomfort that
occurs in the presence of cardiopulmonary and neuromuscular diseases. Dyspnea is
one of the most common and most distressing symptoms experienced by critically
ill patients. Many critically ill patients, particularly those not expected to
survive, become cognitively impaired or unconscious and lose the ability to
report symptoms, although dyspnea can be known only from a patient's report. When
self-reporting ability is lost, the critical care nurse must rely on signs
indicative of a patient's respiratory distress. The critically ill patient unable
to self-report is vulnerable to under-recognition of symptom distress and
subsequent over-treatment or undertreatment. When the patient is dying, there is
only 1 chance to optimize the assessment and treatment of symptoms.
PMID- 29961661
TI - Educational Intervention to Improve Delirium Recognition by Nurses.
AB - BACKGROUND: Delirium poses increased morbidity and mortality risks for
hospitalized patients. Underrecognition by health care providers contributes to
poor outcomes for patients. Little has been published about methods used to teach
health care providers how to screen for delirium using the Confusion Assessment
Method for the Intensive Care Unit (CAM-ICU). OBJECTIVE: To evaluate the
effectiveness of a multimodal educational intervention for nurses in the medical
intensive care unit to improve their knowledge and skills regarding delirium and
delirium recognition. METHODS: An educational intervention was done in the
medical intensive care unit of an academic medical center. Effectiveness was
evaluated via a quasi-experimental design and using preintervention and
postintervention assessments. Procedural correctness of performing the CAM-ICU
delirium screening also was measured. RESULTS: Nurses participated in 1 small
group session (n = 34). Fifteen sessions were conducted from June to September
2016, and assessments were completed before and after the intervention. The
sample consisted of predominantly nurses with a bachelor's degree (56%) who had 1
to 5 years' experience (59%). Mean scores overall and on the knowledge subscale
differed significantly (P < .001) from before to after the intervention. No
correlation was found between demographic groups and score differences. Seventy
nine percent of participants used the tool correctly after the intervention.
CONCLUSIONS: The educational intervention provided for these nurses further
validated published reports of the benefits of an educational program about
delirium. The content of the educational intervention should be targeted for the
setting, the risk factors for the patient population in question, and the
specific delirium screening tool used.
PMID- 29961662
TI - Using Patient Assessment Tools.
PMID- 29961663
TI - Correlation Between mMINDS and CIWA-Ar Scoring Tools in Patients With Alcohol
Withdrawal Syndrome.
AB - BACKGROUND: Many alcohol withdrawal scoring tools are used in hospitalized
patients to assess the severity of alcohol withdrawal and guide treatment. The
revised Clinical Institute Withdrawal Assessment (CIWA-Ar) and the modified
Minnesota Detoxification Scale (mMINDS) are commonly used but have never been
correlated. OBJECTIVE: To determine the strength of correlation between the CIWA
Ar and mMINDS scoring tools in patients with alcohol withdrawal syndrome.
METHODS: A single-center, prospective correlation study conducted at a large
academic medical center. Patients treated for alcohol withdrawal syndrome
according to the Yale Alcohol Withdrawal Protocol were identified daily, and both
the CIWA-Ar and mMINDS were administered at each time point required by the
protocol. Clinical data were obtained from the electronic medical records.
RESULTS: A total of 185 CIWA-Ar and mMINDS scores were collected in 30 patients.
The Pearson correlation coefficient across all scores was 0.82, indicating a
strong correlation. The Pearson correlation coefficient was 0.87 for CIWA-Ar
scores of 10 or less and 0.52 for CIWA-Ar scores above 10. Strong correlations
were also shown for tremor (0.98), agitation (0.84), and orientation (0.87).
CONCLUSIONS: The correlation between the CIWA-Ar and mMINDS tools is strong and
appears to be most robust in patients with CIWA-Ar scores of 10 or less.
PMID- 29961664
TI - Derivation of a PIRO Score for Prediction of Mortality in Surgical Patients With
Intra-Abdominal Sepsis.
AB - BACKGROUND: Mortality in patients with intra-abdominal sepsis remains high.
Recognition and classification of patients with sepsis are challenging; about 70%
of critical care specialists find the existing definitions confusing and not
clinically useful. OBJECTIVE: To assess the usefulness of the predisposition,
infection/injury, response, organ dysfunction (PIRO) concept in surgical
intensive care patients with severe sepsis or septic shock due to an intra
abdominal source. METHODS: Data from 2005 through 2010 of a prospective
observational cohort were reviewed retrospectively. RESULTS: Among 905 patients,
overall mortality was 21.3%, but patients with septic shock had a mortality of
40.6%. The variables in each PIRO subset with P <= .10 were entered into a
stepwise backward elimination logistic regression. A PIRO score was developed
that included the following variables: age greater than 65 years; comorbid
conditions; leukopenia; hypothermia; and cardiovascular, renal, respiratory, and
central nervous system failure. One point was given for each feature detected.
The mean score was significantly higher (P < .001) in non-survivors (3.9) than in
survivors (2.3). When the data were distributed according to PIRO scores,
mortality rate increased (P < .001). The area under the receiver operating
characteristic curve indicated consistent mortality discrimination by PIRO scores
(0.80; 95% CI, 0.79-0.83), outperforming the Acute Physiology and Chronic Health
Evaluation II (0.72; 95% CI, 0.68-0.75) and the Sequential Organ Failure
Assessment (0.72; 95% CI, 0.68-0.76) (P < .001). CONCLUSION: The PIRO score is
useful for predicting mortality in patients with surgically related intra
abdominal sepsis.
PMID- 29961665
TI - Relationships Among Palliative Care, Ethical Climate, Empowerment, and Moral
Distress in Intensive Care Unit Nurses.
AB - BACKGROUND: Intensive care unit nurses experience moral distress when they feel
unable to deliver ethically appropriate care to patients. Moral distress is
associated with nurse burnout and patient care avoidance. OBJECTIVES: To evaluate
relationships among moral distress, empowerment, ethical climate, and access to
palliative care in the intensive care unit. METHODS: Intensive care unit nurses
in a national database were recruited to complete an online survey based on the
Moral Distress Scale-Revised, Psychological Empowerment Index, Hospital Ethical
Climate Survey, and a palliative care delivery questionnaire. Descriptive,
correlational, and regression analyses were performed. RESULTS: Of 288 initiated
surveys, 238 were completed. Participants were nationally representative of
nurses by age, years of experience, and geographical region. Most were white and
female and had a bachelor's degree. The mean moral distress score was moderately
high, and correlations were found with empowerment (r = -0.145; P = .02) and
ethical climate scores (r = -0.354; P < .001). Relationships between moral
distress and empowerment scores and between moral distress and ethical climate
scores were not affected by access to palliative care. Nurses reporting
palliative care access had higher moral distress scores than those without such
access. Education, ethnicity, unit size, access to full palliative care team, and
ethical climate explained variance in moral distress scores. CONCLUSIONS: Poor
ethical climate, unintegrated palliative care teams, and nurse empowerment are
associated with increased moral distress. The findings highlight the need to
promote palliative care education and palliative care teams that are well
integrated into intensive care units.
PMID- 29961666
TI - Collecting Nursing Research Data 24 Hours a Day: Challenges, Lessons, and
Recommendations.
AB - BACKGROUND: Research on many routine nursing interventions requires data
collection around the clock each day (24/7). Strategies for implementing and
coordinating a study 24/7 are not discussed in the literature, and best practices
are needed. OBJECTIVE: To identify strategies incorporated into implementing a
nursing intervention trial 24/7, including key lessons learned. METHODS:
Strategies to facilitate implementation of a clinical trial of a nursing
intervention with patients undergoing mechanical ventilation are shared.
Challenges and changes for future studies also are discussed. RESULTS: Adequate
planning, including a detailed operations manual, guides study implementation.
Staffing is the most challenging and costly part of a study but is essential to a
study's success. Other important strategies include communication among the study
personnel and with collaborators and direct care staff. An electronic method of
recording study-related data also is essential. CONCLUSIONS: A nursing clinical
trial that requires interventions on a 24/7 basis can be done with thorough
planning, staffing, and continuous quality improvement activities.
PMID- 29961667
TI - Family Members' Experiences With Bereavement in the Intensive Care Unit.
AB - BACKGROUND: Losing a loved one in the intensive care unit can be challenging for
families. Providing bereavement support may assist in the grieving process.
OBJECTIVE: To describe family members' experiences with bereavement after the
death of a loved one in the intensive care unit. METHODS: This secondary analysis
used an exploratory, descriptive design to study family members' experiences with
bereavement. Family members of patients from 2 intensive care units in a tertiary
medical center in the western United States participated. Audiotaped telephone
interviews using a semistructured questionnaire were conducted. A qualitative,
descriptive technique was used for data analysis. Two independent raters coded
transcripts of audiotaped interviews with family members about their bereavement
experiences. RESULTS: Seventeen family members participated in the study. Most
participants were female (n = 12; 71%) and spouses of deceased patients (n = 14;
82%), and their mean (SD) age was 62.4 (10.0) years. Three themes emerged: (1)
bereavement was an individual experience; (2) situations occurring during the
intensive care unit encounter remained significant for family members beyond a
year after the death; and (3) social, cultural, spiritual, and religious events
after the death hold importance for families of patients in the intensive care
unit. CONCLUSIONS: Bereavement is a challenging experience for families of
deceased intensive care unit patients. The themes identified in this study add
insight into the experiences of these family members. The results of this study
may guide future interventions to help support bereaved families of intensive
care unit patients.
PMID- 29961668
TI - Disinfection of Blood Pressure Cuffs and Electrocardiographic Telemetry Leads
With 0.5% Hydrogen Peroxide Wipes.
AB - BACKGROUND: Disinfection of frequently touched surfaces in the hospital is
critical for providing safe care. Because of their complex intricate surfaces,
blood pressure cuffs and electrocardiographic telemetry leads may be harder than
other equipment to disinfect. OBJECTIVE: To determine the effectiveness of 0.5%
hydrogen peroxide wipes in cleaning and disinfecting inpatient hospital surfaces,
including hook and loop (Velcro) fasteners of blood pressure cuffs and
electrocardiographic telemetry leads. METHODS: A prospective study of an
inpatient telemetry unit was designed to measure the persistence of a UV
indicator and the presence of bacterial colonization on electrocardiographic
telemetry leads and blood pressure cuffs. Call buttons and patient trays were
used as control surfaces, because they are often touched but are easy to
disinfect via standard practices. RESULTS: A total of 392 samples were collected
between July 11 and August 3, 2016, and cultured for microorganisms. Among the
cultures, 247 (63%) had at least 1 colony-forming unit. After adjustments in a
multivariable analysis, odds of a contaminated surface (>= 10 colony-forming
units) after final cleaning with 0.5% hydrogen peroxide wipes were 3.70 times
greater for patient trays than for blood pressure cuffs (P = .03) and 3.80 times
greater for telemetry leads than for blood pressure cuffs (P = .04). The UV
indicator persisted longer on blood pressure cuffs and telemetry leads than on
patient trays or call buttons (P < .001). CONCLUSION: Wipes with 0.5% hydrogen
peroxide adequately disinfect blood pressure cuffs but not telemetry leads.
PMID- 29961669
TI - Postoperative Bedside Critical Care of Thoracic Surgery Patients.
PMID- 29961670
TI - Skin Impact of Alcohol-Based Hand Rubs vs Handwashing.
PMID- 29961671
TI - Validation of Displayed Electrocardiographic Rhythms at the Central Monitoring
Station.
PMID- 29961672
TI - miR-15b reduces amyloid-beta accumulation in SH-SY5Y cell line through targetting
NF-kappaB signaling and BACE1.
AB - Alzheimer's disease (AD) is the multifactorial neurodegenerative disorder causing
progressive memory loss and cognitive impairment. The aberrant accumulation of
amyloid-beta (Abeta) and neuroinflammation are two major events in AD. BACE1 is
required for the cleavage of amyloid precursor protein (APP) to generate Abeta,
which stimulates the nuclear transcription factor kappaB (NF-kappaB) signaling,
leading to the secretion of inflammatory cytokines. And NF-kappaB can up-regulate
the expression of BACE1. miRNAs are small non-coding RNAs that regulate gene
transcription. miR-15b down-regulates BACE1 expression while it is unclear
whether miR-15b can regulate Abeta in human neuronal cells, and if so, whether it
is by targetting NF-kappaB. SH-SY5Y cell line was transfected with Swedish APP
mutant (APPswe) as an in vitro AD model. Quantitative PCR (qPCR), WB, and ELISA
were used to detected related gene expression intracellularly or in supernatant.
Dual luciferase assay was used to validate miRNA and targets binding. miR-15b
inhibits expression of BACE1and APP. Moreover, the reduced level of Abeta was
observed in response to miR-15b mimics in SH-SH5Y/APPswe cells. miR-15b directly
targetted the conserved Bace1 3'UTR to regulate its expression. In addition, the
inhibition of APPswe-induced secretion of inflammatory cytokines and the
suppression of NF-kappaB activation by miR-15b were validated. And miR-15b
directly targetted the 3'UTRs of NF-kappaB1 and inhibitor of NF-kappaB (IkappaB)
kinase alpha (IKK-alpha), encoding NF-kappaB1 and IKK-alpha, respectively. Our
study suggests that miR-15b inhibits Abeta accumulation through targetting NF
kappaB signaling and BACE1 and serves as a potential molecular target for AD
therapy.
PMID- 29961673
TI - Atherosclerosis in subjects newly diagnosed with human immunodeficiency virus
infection.
AB - HIV infection is associated with the increased risk of cardiovascular disease
(CVD), even in patients successfully treated with the combination antiretroviral
therapy (cART). However, the relationship between HIV, cART, and pathogenesis of
CVD remains controversial. In the present study, we evaluated the carotid intima
media thickness (CIMT), a surrogate marker of atherosclerosis, in HIV-infected
subjects receiving or not receiving cART. One hundred nine newly diagnosed HIV
infected subjects and one hundred nine uninfected age-matched controls (all
males) without the history of CVD, hypertension, or diabetes were recruited into
the present study. Cross-sectional analysis at baseline (BL) showed significantly
increased levels of triglycerides (TG) and decreased levels of high-density
lipoprotein (HDL) in HIV-infected subjects, indicating that these risk factors
for CVD appeared during the undiagnosed period of HIV infection. Nevertheless, no
differences in CIMT were detected between the groups, suggesting that these risk
factors were yet to be translated into the clinical disease. The prospective arm
of the study, which included 37 HIV-infected and 23 uninfected subjects, showed
higher CIMT increase in HIV-infected group than in control group (P=0.0063). This
difference was significant for both cART-treated (P=0.0066) and untreated
(P=0.0246) subgroups relative to the uninfected subjects, but no difference was
found between the HIV-infected subgroups. These results suggest that cART does
not reverse the HIV-induced increase of CIMT. The present study demonstrates that
the progression of atherosclerosis is accelerated in HIV-infected subjects
regardless of treatment.
PMID- 29961676
TI - Fat Metaplasia in Inflammatory Sacroiliitis and in Nonrheumatic Conditions: A
Step Toward Better Characterization.
PMID- 29961675
TI - Chasing the Ghost of Imaging Remission in Rheumatoid Arthritis.
PMID- 29961677
TI - Isolated Cervical Cord Involvement in Primary Central Nervous System Vasculitis.
PMID- 29961674
TI - The diagnostic values of circulating miRNAs for hypertension and bioinformatics
analysis.
AB - Few studies have compared the performances of those reported miRNAs as biomarkers
for hypertension in a same cohort, we aimed to comprehensively examine the
performances of those reported miRNAs as biomarkers for hypertension and identify
the genes and pathways targetted by these miRNAs. Serum samples were collected
from patients hospitalized for hypertension in Zhongshan Hospital. Gene
expressions of 25 miRNAs were compared between hypertension and normal groups.
Receiver operating characteristic (ROC) curves were used to evaluate the accuracy
of those miRNAs as biomarkers for hypertension. miRWALK2.0 and Kyoto Encyclopedia
of Genes and Genomes (KEGG) enrichment analysis were performed to predict the
target genes and pathways of selected miRNAs. A total of 164 participants were
enrolled, amongst which 53 were patients with hypertension, 111 were normal
population. MiR-122-5p (area under curve (AUC): 0.750), miR-199a-3p (AUC: 0.744),
miR-208a-3p (AUC: 0.743), miR-423-5p (AUC: 0.740), and miR-223-5p (AUC: 0.718)
showed better performance than others, and the best performance was the
combination of miR-199a-3p, miR-208a-3p, miR-122-5p, and miR-223-3p (AUC: 0.80).
Pathway analysis revealed that 94 pathways enriched with genes targetted by miR
199a-3p, miR-208a-3p, miR-122-5p, miR-223-5p FoxO signaling was enriched with
genes targetted by all the three miRNAs (miR-199a-3p, miR-208a-3p, miR-122-5p).
The combination of miR-199a-3p, miR-208a-3p, miR-122-5p, and miR-223-3p has a
good diagnostic performance for hypertension, and multitudes of possible
mechanisms/pathways through which dysregulation of these miRNAs may impact risk
of hypertension.
PMID- 29961678
TI - Impairment of Motivational Efforts: Another Complication of Opioid Compromise of
Sleep Quality?
PMID- 29961679
TI - Dr. Rossides, et al reply.
PMID- 29961680
TI - At What Age Was Systemic Lupus Erythematosus Diagnosed in This Cohort?
PMID- 29961681
TI - Advancing the Development of Patient-reported Outcomes for Adult Myositis at
OMERACT 2016: An International Delphi Study.
PMID- 29961682
TI - Dr. Fitzcharles and Dr. Shir reply.
PMID- 29961683
TI - Hospitalization Increases the Risk of Acute Arthritic Flares in Gout: A
Population-based Study over 2 Decades.
AB - OBJECTIVE: To assess in-hospital gout flares in patients with gout. METHODS:
Hospitalizations were evaluated for gout flares in a cohort of Olmsted County,
Minnesota, residents with incident gout in 1989-1992 or 2009-2010. RESULTS: There
were 429 patients followed up to 5 years. Of these, 169 patients experienced 454
hospitalizations. Hospitalization rates increased without reaching statistical
significance from 1989-1992 to 2009-2010 [rate ratio (RR) 1.19, 95% CI 0.98
1.45]. The gout flare rate increased significantly during hospitalization (RR
10.2, 95% CI 6.8-14.5). In-hospital gout flare increased the average hospital
stay by 1.8 days (p < 0.001). CONCLUSION: Hospitalization increased the risk of
gout flares 10-fold. In-hospital gout flares were associated with longer
hospitalization.
PMID- 29961684
TI - Associations Between Cardiorespiratory Fitness and Arterial Stiffness in
Ankylosing Spondylitis: A Cross-sectional Study.
AB - OBJECTIVE: To assess associations between cardiorespiratory fitness (CRF),
measured as peak oxygen uptake (VO2peak), and cardiovascular disease (CVD) risk,
measured by arterial stiffness, in patients with ankylosing spondylitis (AS).
METHODS: VO2peak was assessed by a maximal walking test on a treadmill. Arterial
stiffness was measured noninvasively (Sphygmocor apparatus). Cross-sectional
associations between VO2peak and arterial stiffness were analyzed using backward
multivariable linear regression. RESULTS: Among 118 participating patients, there
were significant inverse associations between VO2peak and arterial stiffness,
independent of traditional CVD risk factors and measures of disease activity.
CONCLUSION: Reduced CRF may be related to increased risk of CVD in AS.
PMID- 29961685
TI - Influence of Disease Manifestations on Health-related Quality of Life in Early
Psoriatic Arthritis.
AB - OBJECTIVE: Psoriatic arthritis (PsA) is a multifaceted disease. Affecting joints,
skin, entheses, and dactylitis, its effect on health-related quality of life
(HRQOL) could be substantial. We aim to assess HRQOL in patients newly diagnosed
with PsA and analyze its associations with disease manifestations. METHODS: Data
collected at time of diagnosis from patients with PsA included in the Dutch south
west Early Psoriatic Arthritis cohort (DEPAR) study were used. HRQOL was assessed
using 8 domains of the Medical Outcomes Study Short Form-36 (SF-36)
questionnaire. Patients were classified based on primary manifestation in
arthritis subtypes (i.e., mono-, oligo-, or polyarthritis) and other subtypes
(i.e., enthesitis, dactylitis, and axial disease). In all patients, presence of
arthritis, enthesitis, dactylitis, psoriasis, and chronic inflammatory back pain
was determined. Multivariable linear regression was used to determine
associations of PsA manifestations with HRQOL. RESULTS: Of 405 patients, primary
manifestation was peripheral arthritis in 320 (78 monoarthritis, 151
oligoarthritis, and 91 polyarthritis), enthesitis in 37, axial disease in 9, and
dactylitis in 39. Mean scores of SF-36 domains were lower than the Dutch
reference population and similar across arthritis subtypes. A higher number of
enthesitis locations and tender joints, and presence of chronic back pain, were
independently associated with worse SF-36 scores. Psoriasis and dactylitis were
not associated with worse scores. CONCLUSION: HRQOL was diminished in PsA at time
of diagnosis compared to the Dutch reference population, and tender joints,
enthesitis at clinical examination, and back pain as indicators of pain affected
HRQOL.
PMID- 29961686
TI - Growth During Tocilizumab Therapy for Polyarticular-course Juvenile Idiopathic
Arthritis: 2-year Data from a Phase III Clinical Trial.
AB - OBJECTIVE: Evaluate growth in patients with polyarticular-course juvenile
idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ) for up to 2 years in
a phase III trial. METHODS: Patients with pcJIA lasting at least 6 months and
inadequate response to methotrexate received open-label TCZ intravenously every 4
weeks (randomly assigned to 8 or 10 mg/kg if they weighed < 30 kg; received 8
mg/kg if they weighed >= 30 kg) for 16 weeks. Patients with JIA American College
of Rheumatology 30 response at Week 16 were randomly assigned to TCZ or placebo
for 24 weeks, with an open-label extension through Week 104. Mean +/- SD height
velocity (cm/yr) and World Health Organization (WHO) height SD score (SDS) were
measured in patients receiving >= 1 dose of TCZ who did not receive growth
hormone and in patients whose baseline Tanner stage was <= 3. RESULTS: The study
included 187 of 188 patients (99.5%) with mean WHO height SDS -0.5 +/- 1.2, which
was unrelated to age or disease duration (Spearman rank correlations r = 0.08 and
r = -0.12, respectively). There were 123 patients at Tanner stage <= 3 at
baseline, among whom 103 completed the study with 2 years of height SDS data.
Mean height SDS increased from baseline to year 2 (+0.40, p < 0.0001). In 74 of
103 patients (72%), height SDS was greater than at baseline, and mean height
velocity was 6.7 +/- 2.0 cm/year. CONCLUSION: Among patients with pcJIA at Tanner
stage <= 3 at baseline, 72% (74/103) had increased height SDS at the end of the
study.
PMID- 29961688
TI - Monitoring of Osteonecrosis in Systemic Lupus Erythematosus: A Systematic Review
and Metaanalysis.
AB - OBJECTIVE: Nontraumatic osteonecrosis (ON) is a well-recognized complication
causing disability and affecting quality of life in patients with systemic lupus
erythematosus (SLE). The aim of this study was to identify the risk factors for
ON, and to identify the minimal investigation(s) needed to optimally monitor the
risk of ON in patients with SLE. METHODS: A systematic review was conducted using
MEDLINE and EMBASE. These databases were searched up to January 2016 using the
Medical Subject Heading (MeSH) terms "Osteonecrosis," "Systemic lupus
erythematosus," and synonymous text words. Randomized controlled trials, case
control, cohort, and cross-sectional studies were included. Risk factors for ON
in patients with SLE were compiled. The quality of each study was assessed using
the Newcastle-Ottawa scale for nonrandomized studies. The quality of evidence of
each risk factor was assessed using the Grading of Recommendations, Assessment,
Development, and Evaluation method. RESULTS: Of the 545 references yielded, 50
met inclusion criteria. Corticosteroid (CS) use may be strongly associated with
ON in patients with SLE. Other clinical variables were moderately associated,
including hypertension, serositis, renal disease, vasculitis, arthritis, and
central nervous system disease. However, the evidence was low to very low in
quality. CONCLUSION: Based on the best evidence available, CS use may be strongly
associated with ON in patients with SLE. Results of this review were considered
in the development of recommendations for the diagnosis and monitoring of
patients with SLE in Canada and will guide clinicians in their assessment of
these patients.
PMID- 29961687
TI - Assessing Vasculitis in Giant Cell Arteritis by Ultrasound: Results of OMERACT
Patient-based Reliability Exercises.
AB - OBJECTIVE: To test the reliability of Outcome Measures in Rheumatology Clinical
Trials (OMERACT) consensus-based ultrasound definitions for normal and vasculitic
temporal and axillary arteries in patients with giant cell arteritis (GCA) and in
controls. METHODS: A preliminary 1-day meeting and a full 3-day meeting
fulfilling OMERACT Ultrasound Group guidelines were held. Temporal and axillary
arteries were examined at 2 timepoints by 12 sonographers on 4 patients with GCA
and 2 controls. The aim was to test inter- and intrareader reliability for normal
findings, halo sign, and compression sign. In both meetings, patients had
established GCA. Pathology was more recent in the full meeting, which was
preceded by 6 h of training. Scanning time was 15-20 min instead of 10-13 min.
RESULTS: In the preliminary exercise, interreader reliabilities were fair to
moderate for the overall diagnosis of GCA (Light kappa 0.29-0.51), and poor to
fair for identifying vasculitis in the respective anatomical segments (Light
kappa 0.02-0.46). Intrareader reliabilities were moderate (Cohen kappa 0.32
0.64). In the main exercise, interreader reliability was good to excellent (Light
kappa 0.76-0.86) for the overall diagnosis of GCA, and moderate to good (Light
kappa 0.46-0.71) for identifying vasculitis in the respective anatomical
segments. Intrareader reliability was excellent for diagnosis of GCA (Cohen kappa
0.91) and good (Cohen kappa 0.71-0.80) for the anatomical segments. CONCLUSION:
OMERACT-derived definitions of halo and compression signs of temporal and
axillary arteries are reliable in recent-onset GCA if experienced sonographers (>
300 examinations) have 15-20 min for a standardized examination with prior
training and apply > 15 MHz probes.
PMID- 29961689
TI - Frequency of Impaired Spinal Mobility in Patients with Chronic Back Pain Compared
to Patients with Early Axial Spondyloarthritis.
AB - OBJECTIVE: To examine the frequency of impaired spinal mobility in patients with
chronic back pain of short duration and to compare it with the frequency of
impaired spinal mobility in patients with axial spondyloarthritis (axSpA),
possible SpA, and no SpA. METHODS: The SpondyloArthritis Caught Early (SPACE)
cohort includes patients with chronic back pain (>= 3 mos, <= 2 yrs, onset < 45
yrs). Spinal mobility was assessed with lateral spinal flexion, chest expansion,
cervical rotation, occiput-to-wall distance, and lumbar flexion. Hip mobility was
assessed with intermalleolar distance. Mobility measures were defined as impaired
if below the 5th percentile reference curve from general population, adjusted for
age and height when appropriate. Proportions of patients categorized with
impaired mobility were examined with chi square. RESULTS: In total, 393 patients
with chronic back pain were included: 142 axSpA, 140 possible SpA, and 111 no
SpA. Impairment in >= 1 mobility measure was present in 66% of all patients. The
most frequently impaired mobility measure was lateral spinal flexion (40%),
followed by chest expansion (22%), cervical rotation (18%), intermalleolar
distance (17%), lumbar flexion (15%), and occiput-to-wall distance (11%). No
statistically significant differences in proportion of patients with impaired
spinal mobility were found between patients with axSpA and the other subgroups in
any of the tests. CONCLUSION: Two out of 3 patients with chronic back pain of
short duration had impaired spinal mobility compared to the general population.
Impaired spinal mobility occurs as often in patients with early axSpA as in other
forms of chronic back pain.
PMID- 29961690
TI - KL-6 But Not CCL-18 Is a Predictor of Early Progression in Systemic Sclerosis
related Interstitial Lung Disease.
AB - OBJECTIVE: The 2 pneumoproteins, KL-6 and CCL-18, are promising biomarkers in
systemic sclerosis (SSc)-related interstitial lung disease (ILD). Our goal was to
determine their predictive significance for forced vital capacity % (FVC%)
decline within the first year of followup in patients with early SSc-ILD.
METHODS: Early SSc patients with imaging-verified ILD enrolled in the Genetics
versus Environment in Scleroderma Outcome Study (GENISOS) cohort were included.
Annualized rate of change in FVC% based on the baseline and followup measurement
within 12-18 months was used as the surrogate outcomes for ILD progression.
RESULTS: Eighty-two early SSc-ILD patients with mean disease duration of 2.3
years were investigated. FVC% change ranged from -23% to 38%. Baseline KL-6
levels were higher in patients than healthy controls (p < 0.0001). Higher KL-6
levels were predictive of faster FVC% decline at the 1-year followup (r = -0.23,
p = 0.037). Upon categorizing KL-6 using a previously published cutoff of 1273
U/ml, its predictive significance remained in the univariable model (b = -0.07, p
= 0.01), indicating that patients with positive KL-6 had on average 7% more
decline in annualized percent change of FVC%. Moreover, KL-6 remained an
independent predictor after adjustment for sex, disease type, anti-Scl-70, and
immunosuppressive treatment status in multivariable models. Although CCL-18 was
higher in patients than controls (p < 0.001), its levels did not predict FVC
decline rate (p = 0.458). CONCLUSION: KL-6 but not CCL-18 is predictive of early
SSc-ILD progression. KL-6 is a promising pneumoprotein that can contribute to SSc
ILD clinical trial enrichment.
PMID- 29961691
TI - Influence of Axial Involvement on Clinical Characteristics of Psoriatic
Arthritis: Analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis
Registry.
AB - OBJECTIVE: We analyzed the characteristics of patients with psoriatic arthritis
(PsA) with and without axial involvement in the US-based Corrona Psoriatic
Arthritis/Spondyloarthritis Registry. METHODS: All patients were included who had
PsA and data on axial involvement, defined as physician-reported presence of
spinal involvement at enrollment, and/or radiograph or magnetic resonance imaging
showing sacroiliitis. Demographics, clinical measures, patient-reported outcomes,
and treatment characteristics were assessed at enrollment. RESULTS: Of 1530
patients with PsA, 192 (12.5%) had axial involvement and 1338 (87.5%) did not.
Subgroups were similar in sex, race, body mass index, disease duration, presence
of dactylitis, and prevalence of most comorbidities. However, patients with axial
involvement were younger and more likely to have enthesitis, a history of
depression, and more frequently used biologics at enrollment. They were also more
likely to have moderate/severe psoriasis (body surface area >= 3%, 42.5% vs
31.5%) and significantly worse disease as measured by a lower prevalence of
minimal disease activity (30.1% vs 46.2%) and higher nail psoriasis scores
[visual analog scale (VAS) 11.4 vs 6.5], enthesitis counts (5.1 vs 3.4), Bath
Ankylosing Spondylitis Disease Activity Index (4.7 vs 3.5) scores, Bath
Ankylosing Spondylitis Functional Index (3.8 vs 2.5) scores, C-reactive protein
levels (4.1 vs 2.4 mg/l), and scores for physical function (Health Assessment
Questionnaire, 0.9 vs 0.6), pain (VAS, 47.7 vs 36.2), and fatigue (VAS, 50.2 vs
38.6). CONCLUSION: Presence of axial involvement was associated with a higher
likelihood of moderate/severe psoriasis, with higher disease activity and greater
effect on quality of life. These findings highlight the importance of monitoring
patients with PsA for signs of axial symptoms or spinal involvement.
PMID- 29961692
TI - Maternal and Fetal Outcomes in a Cohort of Patients Exposed to Tumor Necrosis
Factor Inhibitors throughout Pregnancy.
AB - OBJECTIVE: Tumor necrosis factor inhibitors (TNFi) are increasingly used in
pregnancy but are frequently withheld in the second or third trimesters. We
evaluated the maternal and fetal outcomes of women who continued their TNFi
throughout pregnancy compared to women who interrupted TNFi during pregnancy.
METHODS: We retrospectively analyzed the outcomes of women seen in clinic with
rheumatoid arthritis (RA), psoriatic arthritis, juvenile idiopathic arthritis
(JIA), or ankylosing spondylitis, who were exposed to TNFi during pregnancy. We
separated pregnancies into 2 groups based on the level of TNFi exposure and
compared outcomes. RESULTS: In Group 1 (TNFi exposure in first trimester only),
11 women had 14 pregnancies and 12 live births. There were 2 first-trimester
losses (2/14, 14%), one in the setting of active RA. Five pregnancies (5/14,
35.7%) were complicated by a disease flare. Eight patients (8/12, 66%) flared
postpartum. In Group 2 (TNFi exposure throughout pregnancy), 29 women had 32
pregnancies and 34 live births. Three (3/28, 10.7%) adverse pregnancy outcomes
were reported in 2 patients. One patient had a twin pregnancy and delivered at 33
weeks after developing preterm premature rupture of membranes at 32 weeks in the
setting of a JIA flare. Her second pregnancy was complicated by active JIA before
and throughout gestation, and hemolysis, elevated liver enzyme levels, and low
platelet levels (HELLP) syndrome at 39 weeks. Another patient with comorbid
antiphospholipid syndrome underwent a cesarean birth at 36 weeks for suspicion of
HELLP syndrome. Six (6/32, 18.7%) postpartum flares occurred. CONCLUSION: Women
who discontinued their TNFi during pregnancy had a higher risk of peri- or
postpartum flare compared to those who continued their TNFi throughout pregnancy.
PMID- 29961693
TI - Increased Rates of Both Knee and Hip Arthroplasties in Older Patients with
Ankylosing Spondylitis.
AB - OBJECTIVE: To determine the risks of primary total hip arthroplasty (THA) and
total knee arthroplasty (TKA) in older patients with ankylosing spondylitis (AS).
METHODS: We used administrative data from 1999 to 2013 on US Medicare
beneficiaries to identify patients (< 75 yrs old) with AS and a comparison group
without AS. Rates of primary THA and primary TKA were computed for each group,
and standardized for age, sex, and race. We also examined risks of primary TKA
among patients with AS by their THA status. RESULTS: We analyzed 52,568 patients
with AS and 4,617,179 patients without AS. Between 1999 and 2013, the
standardized incidence of primary THA in patients with AS doubled from 4.5 per
1000 patient-years (PY) to 9.6 per 1000 PY. Rates of primary TKA were higher in
patients with AS than controls in all years. In 2013, the standardized incidence
of primary TKA in AS was 12.3 per 1000 PY versus 5.7 per 1000 PY in the
comparison group (RR 2.14, 95% CI 1.93-2.38). Rates of primary TKA were twice as
high among patients with AS and THA than among those without THA (20.4 vs 10.2
per 1000 PY). CONCLUSION: Rates of THA in older patients with AS doubled over
recent years, outpacing the increase in the general population. Rates of TKA were
also substantially higher in older patients with AS. The increased risk of TKA in
AS may be a consequence of damage from knee inflammation, or alterations in lower
extremity biomechanics due to hip arthritis.
PMID- 29961694
TI - Sarcoidosis in Patients with Antisynthetase Syndrome: Presentation and Outcome.
AB - OBJECTIVE: To investigate the uncommon co-occurrence of antisynthetase syndrome
(AS) and sarcoidosis. METHODS: From 2000 to 2015, patients with sarcoidosis were
extracted from a retrospective multicentric cohort of 352 patients with AS.
RESULTS: Ten patients (2.8%; 6 men, 8 whites, 5 smokers, median age 50 yrs) had
both AS and sarcoidosis. Most of the time, sarcoidosis and AS occurred
simultaneously (n = 7). Antibody testing revealed anti-Jo1 (n = 5), anti-PL12 (n
= 4), or anti-PL7 (n = 1). Finally, no patient had a worsening of muscular
condition, 5 patients presented respiratory deterioration, 3 remained stable, and
2 showed improvement. CONCLUSION: Sarcoidosis may be underdiagnosed in patients
with AS.
PMID- 29961697
TI - Bylaws of the American Dental Education Association: (With changes approved by
the 2018 House of Delegates).
PMID- 29961698
TI - ADEA Mission, Strategic Directions, and Key Priorities, 2015-18.
PMID- 29961696
TI - Do Poor Prognostic Factors in Rheumatoid Arthritis Affect Treatment Choices and
Outcomes? Analysis of a US Rheumatoid Arthritis Registry.
AB - OBJECTIVE: To characterize patients with rheumatoid arthritis (RA) by number of
poor prognostic factors (PPF: functional limitation, extraarticular disease,
seropositivity, erosions) and evaluate treatment acceleration, clinical outcomes,
and work status over 12 months by number of PPF. METHODS: Using the Corrona RA
registry (January 2005-December 2015), biologic-naive patients with diagnosed RA
having 12-month (+/- 3 mos) followup were identified and categorized by PPF (0-1,
2, >= 3). Changes in medication, Clinical Disease Activity Index (CDAI), and work
status (baseline-12 mos) were evaluated using linear and logistic regression
models. RESULTS: There were 3458 patients who met the selection criteria: 1489
(43.1%), 1214 (35.1%), and 755 (21.8%) had 0-1, 2, or >= 3 PPF, respectively. At
baseline, patients with >= 3 PPF were older, and had longer RA duration and
higher CDAI versus those with 0-1 PPF. In 0-1, 2, and >= 3 PPF groups,
respectively, 20.9%, 23.2%, and 26.5% of patients received >= 1 biologic (p =
0.011). Biologic/targeted synthetic disease-modifying antirheumatic drug
(tsDMARD) use was similar in patients with/without PPF (p = 0.57). After
adjusting for baseline CDAI, mean (standard error) change in CDAI was -4.95
(0.24), -4.53 (0.27), and -2.52 (0.34) for 0-1, 2, and >= 3 PPF groups,
respectively. More patients were working at baseline but not at 12-month followup
in 2 (13.9%) and >= 3 (12.5%) versus 0-1 (7.3%) PPF group. CONCLUSION: Despite
high disease activity and worse clinical outcomes, number of PPF did not
significantly predict biologic/tsDMARD use. This may warrant reconsideration of
the importance of PPF in treat-to-target approaches.
PMID- 29961695
TI - Reproducibility and Utility of the 6-minute Walk Test in Systemic Sclerosis.
AB - OBJECTIVE: To assess the reproducibility and the utility of the 6-minute walk
test (6MWT) in systemic sclerosis (SSc). METHODS: All patients with SSc who
underwent at least two 6MWT within a minimum 3-month interval plus simultaneous
routine clinical, biological, and functional evaluations were consecutively
enrolled in this observational study over 6 years. Following American Thoracic
Society guidelines, each 6MWT was repeated twice to assess the 6-minute walk
distance (6MWD) reproducibility, with the highest value being reported for
subsequent analysis. RESULTS: Among 56 (38 female) included patients aged 46 +/-
SD 12.7 years, with 17 +/- 10 modified Rodnan skin score (mRSS) and 1 +/- 0.8
Scleroderma Health Assessment Questionnaire (SHAQ) at first referral, 277 6MWT
evaluations (5 +/- 3.9 6MWT per patient) were performed over 23 +/- 22.5 months
followup. Meanwhile, 8 deaths (87.5% SSc-related) occurred. The mean 6MWD
absolute value was 457 +/- 117 m with a 4 +/- 2.2 mean Borg dyspnea score. The
6MWD intraclass correlation coefficient was 0.996 (95% CI 0.995-0.999, p <
0.0001). In multivariate linear regression analysis, these factors were
independently associated with a lower 6MWD: sex (R2 = 0.47, p < 0.0001), mRSS (R2
= 0.47, p = 0.008), tendon friction rub (R2 = 0.47, p = 0.003), SHAQ (R2 = 0.47,
p = 0.02), muscle disability score (R2 = 0.47, p = 0.03), DLCO% (R2 = 0.47, p =
0.0008), and left ventricular ejection fraction (R2 = 0.47, p = 0.006). The 6MWD
at first referral was an independent predictor for the overall mortality (HR
0.99, 95% CI 0.988-0.999) and the SSc-related mortality (HR 0.99, 95% CI 0.988
0.999). CONCLUSION: We show strong reproducibility for the 6MWD and confirm the
6MWT utility to assess the overall prognosis of patients with SSc.
PMID- 29961706
TI - Exhibit 9: ADEA Competency Documents.
PMID- 29961707
TI - Exhibit 10: ADEA Principles for Accreditation in Dental Education: (As approved
by the 1997 ADEA House of Delegates).
PMID- 29961708
TI - Exhibit 11: ADEA Policy Statements.
PMID- 29961709
TI - Exhibit 12: ADEA Position Papers.
PMID- 29961713
TI - Editors' Note.
PMID- 29961714
TI - "This Fathom-Long Body": Bodily Materiality and Ascetic Ideology in Medieval
Chinese Buddhist Scriptures.
AB - An outside observer might be excused for assuming that Buddhists, being focused
on transcendence, would have little interest in investigating the body's
structure or constituent parts in any detail. However, nothing could be further
from the truth. Bodies and body parts have in fact long been ubiquitous subjects
of contemplation, speculation, and veneration in Buddhist circles. This article
discusses representative examples of Chinese Buddhist scriptures from the
medieval period that forward an ascetic ideology, with special attention to how
the corporeal body is spoken about in such texts. It shows that the very Buddhist
writings that were most concerned with teaching ascetics how to transcend the
material world in fact focused a great deal of meticulous attention on the
corporeal body and drew heavily on Indian medical concepts in forwarding that
agenda.
PMID- 29961712
TI - ERRATUM.
PMID- 29961715
TI - Leprosy's Untainted Child.
AB - In the face of an obdurate disease, the Mission to Lepers made a virtue out of
"saving" children from leprosy and from paganism by separating them from their
parents so that they became a source of publicity, sponsorship, and fund-raising.
This policy transformed a benevolent work of mercy into a professional one, for
it soon became clear that children separated from their parents did not develop
leprosy. Consequently, the asylum became a site where scientific conclusions were
made about the transmission of the disease, and the authority of the mission was
enhanced at international medical conferences. This nascent professionalism
became sufficient for the Philippines to also be persuaded to remove children
from their leprosy-infected parents. In turn, Culion-based research on the
observations of children ensured the authority of the American and Philippine
doctors in informing decisions made by the League of Nations and later the World
Health Organization.
PMID- 29961716
TI - Religion, Medicine, and Politics: Catholic Physicians' Guilds in America,1909-32.
AB - In 1909 the first Catholic physicians' guild formed in New York City. By 1911
guilds could be found in Philadelphia and Boston. They acted as professional
organizations as well as brotherhoods built on a set of shared religious and
moral convictions. They brought moral perspectives from Catholic doctrine into
critical conversation with their medical work. By 1931, enough enthusiasm existed
to form the National Federation of Catholic Physicians' Guilds (NFCPG). The
creation of NFCPG marked a clear effort to insert Catholic values into America's
health care debates. Focusing on the Philadelphia and Boston guilds, and with the
use of archival collections at the Boston and Philadelphia archdioceses, this
article examines the origins of the guild movement. Over the first several
decades of their existence the guilds became an increasingly politically savvy
force in American health care as they worked to influence local, state, and
federal health policies surrounding women's health care.
PMID- 29961717
TI - Swann Song: Antibiotic Regulation in British Livestock Production (1953-2006).
AB - Antibiotics have played a significant yet ambivalent role in Western livestock
husbandry. Mass introduced to agriculture to boost animal production and reduce
feed consumption in the early 1950s, agricultural antibiotics were soon accused
of selecting for bacterial resistance, causing residues and enabling bad animal
welfare. The dilemma posed by agricultural antibiotic regulation persists to this
day. This essay traces the history of British antibiotic regulation from 1953 to
the influential 1969 Swann report. It highlights the role that individual experts
using bacteriophage typing played in warning about the mass selection for
bacterial resistance on farms and the response of a corporatist system, whose
traditional laissez-faire arrangements struggled to cope with the risk posed by
bacterial resistance. In addition to contextualizing the Swann report's origins,
the essay also discusses the report's fate and implications for current
antibiotic regulation.
PMID- 29961718
TI - Some Notes on Papyrus Ebers, Ancient Egyptian Treatments of Migraine, and a
Crocodile on the Patient's Head.
AB - Modern literature about the history of migraine treatments often starts with an
ancient Egyptian remedy said to be from Papyrus Ebers that involves crocodiles
that should be wrapped around the head. A fresh look on this treatment shows the
need for revision on many points, including the source of the remedy, its content
and meaning, and further implications for the history of Papyrus Ebers.
PMID- 29961719
TI - News And Events.
PMID- 29961720
TI - Memento Mutter.
PMID- 29961722
TI - Disability and Dissent in Ann Petry's The Street.
AB - I argue that Ann Petry in her novel The Street (1946) portrays chronic illness,
disfigurement, and disability as embodied effects of racism resulting from labor
exploitation, crowded and unsafe housing conditions, and lack of access to
nourishing food and respectful, thorough, and effective health care. Further,
Petry conveys that Western medicine (as practiced in the United States)
reproduces and maintains white supremacy through mechanisms including how
treatment resources are allocated, how medical institutions collaborate with law
enforcement officials and institutions, and how medical professionals and spaces
authorize the objectification of Black bodies. Some of the conditions Petry
portrays as disabling are not recognized by Western medicine or measured in
health disparities research; other conditions, Petry shows, are misrecognized by
those discourses. Thus, Petry's novel challenges the medical model of disability
while also urging a more expansive understanding of what should be recognized as
an embodied effect of racism.
PMID- 29961723
TI - Mary Todd Lincoln, Elizabeth Keckley, and America's Psychiatric Republic.
AB - This article reveals how Elizabeth Keckley framed American citizenship as a
psychiatric rather than political category. In Behind the Scenes (1868), Keckley
emblematizes Mary Todd Lincoln's "scandalous" behavior to describe and critique
what I call the psychiatric republic: a politico-economic paradigm that
paradoxically condemns women as mad, often for expressing the very traits
required of men elected to public office, while simultaneously positing feminine
virtues as foundational for republican citizenship. Focusing on how notions of
civic femininity were originally linked to psychiatric nosology, I show how
nineteenth-century women were circumscribed temporally in a seemingly inescapable
loop of diagnosis, treatment, and moral refinement. The spectacular case of Mary
Todd Lincoln is an extreme example of how women were considered mentally unstable
enough to merit exclusion from civic life but were also forced to perform in cure
cultures that would ostensibly ready them for civic duties predicated on rational
democratic subjecthood.
PMID- 29961724
TI - Utopian Literature and Bioethics: Exploring Reproductive Difference and Gender
Equality.
AB - This essay explores how feminist utopian literature can inform bioethical debates
regarding the fundamental differences between female and male experiences of
human reproduction, focusing on the use of biological and technological methods
to redress natural inequalities arising from biological difference. Inherently
speculative, utopian fiction serves as a useful tool for interrogating social and
political attitudes toward procreation and childrearing, adopting a similar
degree of abstraction as a philosophical thought experiment. Thus, there is the
potential for bioethicists to engage more thoroughly with this form of literature
in order to communicate key ethical issues related to reproductive rights and
sexual equality.
PMID- 29961725
TI - The Carnivalesque in Illness: Hollis Seamon's Somebody Up There Hates You.
AB - This article analyzes Hollis Seamon's Somebody Up There Hates You in light of
Mikhail Bakhtin's theory of the carnivalesque as it is developed both in Rabelais
and His World and in Problems of Dostoevsky's Poetics. The novel shows the power
of carnivalesque episodes and ironic laughter to question both the conventional
approach to illness and death, and to illness literature in general. However, it
also exposes the limits of parody and laughter in the face of death-no matter how
regenerating this carnivalesque novel may prove to be for literature as a whole.
PMID- 29961726
TI - Of Drugs and Droogs: Cultural Dynamics, Psychopharmacology, and Neuroscience in
Anthony Burgess's A Clockwork Orange.
AB - Anthony Burgess's A Clockwork Orange is rarely considered in terms of
psychopharmacology. Furthermore, the connection between the novel and the
development of neuroscience-including the use of drugs that affect the brain-has
yet to be considered. This essay explains the function and representation of
drugs in the novel within the context of neuroscience's development during the
1960s. I argue that the novel engages the dynamics among psychopharmacology,
neuroscience, and psychiatry, and investigates how these specialties function
within Western culture to mediate between dominant and subordinate divisions. As
such, a neuroscientific reading of A Clockwork Orange articulates how
counterculture perverts psychopharmacology, driving it away from the normalizing
discourses of psychiatric power (as it is used to correct deviant mental states).
Simultaneously, it demonstrates the failures of the politics of a reactionary,
fear-based neuroscience. Ultimately, the novel both reflects on and intervenes in
a critical biopolitical shift in regulating the brain.
PMID- 29961727
TI - Traces of Stigma in John Banville's The Sea.
AB - Despite acknowledging the centrality of Anna's illness in studies of John
Banville's The Sea, scholars have not attended to the close relationship between
Anna's cancer and her husband Max's process of self-stigmatization. Drawing on
Paul Ricoeur's notion of the trace, I analyze Max's experience of his wife's
illness to show how Banville depicts disease imprinting psychic traces not only
on the patient but also on his/her family. My main contention is that an assay of
Max's self-stigma creates new insights into The Sea that show how the novel's
superb reflections on disease, stigma, pain, suffering, age, death, and artistic
creation promote a narrative destabilization of time categories. This
destabilization underscores the fact that consciousness of finitude is inherent
in the human experience-not just in the late stages of one's life but throughout
the entire life cycle.
PMID- 29961728
TI - "There Is No Miracle More Cruel Than This": Readian Relaxation and Maternal
Agency in Plath's Three Women.
AB - In this article, I contend that Plath's Three Women (1962) stages a poetic
commentary on the theory of natural childbirth pioneered by Dr. Grantly Dick Read
and popularized during the mid-1950s in Great Britain and the United States as an
alternative to the "Twilight Sleep." Plath annotated Read's bestseller Childbirth
Without Fear (1959) and attended relaxation classes before the birth of her
daughter Frieda; however, the long poem has yet to be read in terms of this
medical intertext. As this article demonstrates, treating Plath's poem alongside
Read's popular manual pushes us to consider poetry's (generic) place in making
legible psychologically complex embodied states. Although Read is not directly
referenced, I argue that Three Women wrestles with the psychological implications
of this obstetrician's concept of the Fear-Tension-Pain Syndrome and the
antenatal curriculum he developed to end such anxiety-produced suffering.
PMID- 29961729
TI - An Economy of Illness: The Poetics of Women in Pain.
AB - This essay examines the position of illness within a capitalist economy,
exploring how labor, production, and consumption change through the bodily
experiences of illness. Using contemporary poetry by Elizabeth Arnold and Anne
Boyer, I suggest first that the experience of illness places women in an
alternative economy, not unlike the familiar ways in which women are routinely
devalued when their labor is under-appreciated or under(/un)compensated. I argue
that being ill often challenges the productivity required by capitalism, and that
as a response, experiences of illness play a role in the formation of an
alternative economy. Within these new economic structures, affective experiences
of pain and disgust-typically devalued in a capitalist economy-become
foundational features of taste formation. The poets I examine here explore this
complicated affect to suggest that experiences of pain can have important
economic and affective effects.
PMID- 29961730
TI - Showing that Medical Ethics Cases Can Miss the Point: Rewriting Short Stories as
Cases.
AB - I propose a new role for literature in medical ethics: rewriting short stories as
ethics cases. This activity is instructive for its power to show that our
standard ways of analyzing cases can overlook deeper ethical problems, such as
those the short stories raise. To illustrate this claim, I begin by distilling
Richard Selzer's story "Fetishes" to an ethics case. Then, using principle-based
ethics as a representative analytical framework, I argue that a typical
principlist's response to the "Fetishes" case misses the point, failing to
address insidious issues like physician arrogance and patient mistrust. By
comparing short story and case, we are led to wonder anew whether ethics cases
that represent real events might also fail to probe to the heart of the matter.
Thus, rewriting short stories as ethics cases can inculcate a healthy skepticism
as to whether any case has succeeded in conveying what is most at stake.
PMID- 29961731
TI - Printing Parasites: Hookworm and Public Health Narratives in Southern Fiction.
AB - During the early twentieth century, public health campaigns taught Americans from
all strata of society to recognize that a great threat to the health and
prosperity of the South was not an enemy abroad, but rather a bloodsucking
parasite living underfoot in Southern soil: hookworm. According to the
information widely disseminated by these campaigns, hookworm infection was
responsible for the physical "backwardness" of Southern men, women, and children.
By linking physical and cognitive symptoms to a parasitic source, the public
health campaign introduced a new literary tool for constructing characters who
are not "quite right" that continues to be employed in contemporary fiction. This
paper focuses on the so-called "lazy man's disease" (hookworm) and takes the work
of William Faulkner as a case study to demonstrate how authors deployed a
figurative form of hookworm to construct disabled, poor, and degenerate
characters.
PMID- 29961732
TI - Not Playing Around: Games in Graphic Illness Narratives.
AB - Why do recent graphic narratives about illness play with metaphors of merry-go
rounds, board games, and games of pretend and performance to explain the
experience of being ill? Play and game typically associate with nostalgia, with
pleasure, and with a sense of freedom, none of which come to mind as viable
images to discuss a struggle with difficult physical and mental illnesses.
Acclaimed graphic narratives including Miriam Engelberg's Cancer Made Me a
Shallower Person (2006), Daryl Cunningham's Psychiatric Tales (2011), Ellen
Forney's Marbles (2012), Marisa Acocella Marchetto's Cancer Vixen (2006), and
Brian Fies's Mom's Cancer (2006) use the rich narrative ambiguities of game
situations to work against the grain, correlating the gap between "player" and
"played" with the gap between an active, organically healthy self and a self
being unmade by illness.
PMID- 29961734
TI - How much self-poisoning attempts are visible in Iran?
AB - BACKGROUND: Stigma of suicide attempt (SA) results in not asking friends and
relatives for help. Others' awareness of an individual's SA sometimes can solve
his/her problems and reduce rates of SA. This study is intended to examine the
degree of SA visibility through deliberate self-poisoning (DSP), which is the
most common method of SA in Iran. METHODS: In order to study visibility, all
individuals who had attempted to suicide by DSP and had been referred to the
western Iran poisoning center during April-June, 2016 were entered to the study.
A female and a male interviewer experienced in role-playing were recruited to
interview clients, each with clients of their own gender, in order to increase
compliance and information accuracy. Multivariate Poisson Regression was used to
identify visibility determinants. RESULTS: Among 100 subjects interviewed, 10
denied SA. Regardless of those denying SA, self-poisoning visibility factor (SVF)
was 26.6% (21.7-31.5) which decreased to 23.9% (19.7-28.1) after considering
those individuals who denied SA. The highest values of SVF were observed in
subjects poisoned by toxins, alcohol and illegal drugs, respectively. In the
multivariate model, the value of SVF increased with an increase in age (IRR=1.03,
95% CI: 1.02-1.04), having history of SA (IRR=1.18, 95% CI: 1.07-1.30), and being
married (IRR=1.70, 95% CI: 1.05-1.29). CONCLUSIONS: Lower values of SVF of DSP
indicate that individuals committing suicide do not ask others for help and
saying their SA intents. The higher the degree of visibility, the lower the rates
of committing and repeating SAs. To increase the visibility of SA, therefore, the
one way is to prevent and reduce SA repetition.
PMID- 29961735
TI - Evaluation of Ataxia in Mild Ischemic Stroke Patients Using the Scale for the
Assessment and Rating of Ataxia (SARA).
AB - OBJECTIVE: To demonstrate the utility of Scale for the Assessment and Rating of
Ataxia (SARA) for evaluation of posterior circulation-related features in
patients with mild stroke. METHODS: Forty-five subjects, diagnosed with acute
infarction in the cerebellum, basis pontis, thalamus, corona radiata, posterior
limb of internal capsule, and their National Institutes of Health Stroke Scale
(NIHSS) scores <=5 were enrolled. SARA scores were graded by the cut-off value of
severity in dependency of activities of daily living (ADL). SARA, Berg Balance
Scale (BBS), Timed Up-and-Go (TUG), and Trunk Control Test (TCT) were correlated
in regression analysis with the modified Rankin Scale (mRS) at discharge.
Correlation between SARA and other tools was analyzed. Patients were divided
based on mRS at admission (group A, mRS 0-2; group B, mRS 3-5). Scores between
the two groups were compared. RESULTS: Among the subjects, 48.9% (22/45) scored
above 5.5 on SARA, and even 11.1% (5/45) scored higher than 14.25, which is the
cut-off value of 'severe dependency' in ADL. SARA showed significant value for
prediction of mRS at discharge. SARA was correlated with BBS (r=-0.946, p<0.001),
TUG (r=-0.584, p<0.001), and TCT (r=-0.799, p<0.001). The SARA, BBS, TUG, and TCT
scores between were lower in group B than in group A patients. SARA as well as
BBS, TUG, and TCT reflect the functional severity of all patients. CONCLUSION:
SARA is a complementary tool for evaluation of the severity of ataxia in mild
stroke patients with features of posterior circulation.
PMID- 29961736
TI - Quantitative Evaluation of Post-stroke Spasticity Using Neurophysiological and
Radiological Tools: A Pilot Study.
AB - OBJECTIVE: To determine the possibility of a new measurement tool using
electromyography and ultrasonography for quantitative spasticity assessment in
post-stroke patients. METHODS: Eight hemiplegic stroke patients with ankle
plantarflexor spasticity confirmed by a Modified Ashworth Scale (MAS) were
enrolled. Spasticity was evaluated using the MAS and Modified Tardieu Scale
(MTS). Each subject underwent surface electromyography (sEMG) using the Brain
Motor Control Assessment (BMCA) protocol and was compared with a healthy control
group. Using ultrasonography, muscle architecture and elasticity index were
measured from the medial gastrocnemius muscle (GCM) on the affected and
unaffected sides. RESULTS: MAS and MTS revealed significant correlation with sEMG
activity. The fascicle length and pennation angle were significantly decreased in
the medial GCM on the hemiplegic side compared with the unaffected side. The
elasticity index of the spastic medial GCM was significantly increased compared
with the unaffected side. The MTS X and R2-R1 values were significantly
correlated with the elasticity index in the hemiplegic GCM. The relationship
between clinical evaluation tools and both BMCA and sonoelastography was linear,
but not statistically significant in the multiple regression analysis.
CONCLUSION: The BMCA protocol and ultrasonographic evaluation provide objective
assessment of post-stroke spasticity. Further studies are necessary to conduct
accurate assessment and treatment of spasticity.
PMID- 29961737
TI - Changes in Diffusion Metrics of the Red Nucleus in Chronic Stroke Patients With
Severe Corticospinal Tract Injury: A Preliminary Study.
AB - OBJECTIVE: To explore plastic changes in the red nucleus (RN) of stroke patients
with severe corticospinal tract (CST) injury as a compensatory mechanism for
recovery of hand function. METHODS: The moderate group (MG) comprised 5 patients
with synergistic hand grasp movement combined with limited extension, and the
severe group (SG) included 5 patients with synergistic hand grasp movement alone.
The control group (CG) included 5 healthy subjects. Motor assessment was measured
by Motricity Index (MI). Diffusion tensor imaging was analyzed using fractional
anisotropy (FA) and radial diffusivity (RD) in the individual regions of interest
(ROIs)-bilateral internal capsule and anterior pons for CST injury and bilateral
RN for rubrospinal tract (RST) injury. RESULTS: The SG showed a significantly
lower MI score than the MG mainly due to differences in hand subscores.
Significantly reduced FA was observed in both MG and SG compared with CG, while
SG showed increased MD and RD in the affected ROIs of CST, and increased FA on
the unaffected side compared with CG. However, in the RN ROI, a significantly
increased FA and decreased RD on the unaffected side similar to the affected side
were found only in the SG. The relative index of FA was lower and RD in SG was
higher than in CG in RST. CONCLUSION: The diffusion metrics of RST showed changes
in patients with severe CST injury, suggesting that RST may play a role in the
recovery of hand function in patients with severe CST injury.
PMID- 29961738
TI - Efficacy and Safety of Caregiver-Mediated Exercise in Post-stroke Rehabilitation.
AB - OBJECTIVE: To assess the efficacy and safety of our 4-week caregiver-mediated
exercise (CME) in improving trunk control capacity, gait, and balance and in
decreasing concerns about post-stroke falls when there is an increase in its
efficacy. METHODS: Acute or subacute stroke survivors were assigned to either the
trial group (n=35) or the control group (n=37). Changes in Modified Barthel Index
(MBI), Functional Ambulation Categories (FAC), Berg Balance Scale (BBS), and
Trunk Impairment Scale (TIS) scores at 4 weeks from baseline served as primary
outcome measures. Correlations of primary outcome measures with changes in Fall
Efficacy Scale-International (FES-I) scores at 4 weeks from baseline in the trial
group served as secondary outcome measures. Treatment-emergent adverse events
(TEAEs) served as safety outcome measures. RESULTS: There were significant
differences in changes in MBI, FAC, BBS, TIS-T, TIS-D, TIS-C, and FES-I scores at
4 weeks from baseline between the two groups (all p<0.0001). There were no
significant (p=0.0755) differences in changes in TIS-S scores at 4 weeks from
baseline between the two groups. MBI, FAC, BBS, and TIS scores showed
significantly inverse correlations with FES-I scores in patients receiving CME.
There were no TEAEs in our series. CONCLUSION: CME was effective and safe in
improving the degree of independence, ambulation status, dynamic and static
balance, trunk function, and concerns about post-stroke falls in stroke
survivors.
PMID- 29961739
TI - Changes in Hyolaryngeal Movement During Swallowing in the Lateral Decubitus
Posture.
AB - OBJECTIVE: To investigate the differences in hyolaryngeal kinematics at rest and
during swallowing in the upright sitting (UP) and the lateral decubitus (LD)
postures in healthy adults, and delineating any potential advantages of
swallowing while in the LD posture. METHODS: Swallowing was videofluoroscopically
evaluated in 20 healthy volunteers in UP and LD postures, based on the movements
of hyoid bone, vocal folds, and the bolus head. Parameters included the
Penetration-Aspiration Scale (PAS), horizontal and vertical displacement,
horizontal and vertical initial position, horizontal and vertical peak position,
time to peak position of the hyoid bone and vocal folds, and pharyngeal transit
time (PTT). RESULTS: Nine participants were rated PAS 2 in the UP and 1 was rated
PAS 2 in the LD (p=0.003) at least 1 out of 3 swallows each posture. The hyoid
and vocal folds showed more anterior and superior peak and initial positions in
the LD. In addition, swallowing resulted in greater vertical and smaller
horizontal displacement of the hyoid in LD posture compared with UP. Time to peak
position of the hyoid was shorter in LD. The maximal vertical and horizontal
displacement of the vocal folds, and PTT were comparable between postures.
CONCLUSION: The results showed that the peak and initial positions of the hyoid
and larynx and the pattern of hyoid movement varied significantly depending on
the body postures. This study suggests that the LD posture was one of the safe
feeding postures without any increased risk compared with UP posture.
PMID- 29961740
TI - Relationship Between Swallowing Function and Maximum Phonation Time in Patients
With Parkinsonism.
AB - OBJECTIVE: To identify the relationship between maximum phonation time (MPT) and
swallowing function, as well as the elements of swallowing, in order to provide a
rationale for speech therapy in patients with Parkinsonism manifesting dysphagia.
METHODS: Thirty patients with Parkinsonism who underwent speech evaluation and
videofluoroscopic swallowing study (VFSS) were recruited. The MPT, the longest
periods of sustained pronunciation of /aa/, was evaluated. The VFSS was evaluated
using Penetration Aspiration Scale (PAS), National Institutes of Health
Swallowing Safety Scale (NIH-SSS), and Videofluoroscopic Dysphagia Scale (VDS).
The relationship between dysphagia scales and MPT was analyzed using Pearson
correlation. The difference in VDS variables between subgroups (Parkinson disease
or Parkinsonian syndrome, independent or dependent ambulation, and normal or
abnormal MPT) and the difference in MPT between subgroups based on the VDS
variables were analyzed using the independent t-test. RESULTS: Bolus formation
and laryngeal elevation functions were significantly higher in the normal MPT
group compared with the impaired group. In the VDS variables, patients with
intact bolus formation, oral transit time, pharyngeal swallow triggering, and
laryngeal elevation showed significantly longer MPTs compared with the impaired
groups. In addition, MPT was significantly correlated with the VDS and modestly
correlated with the NIH-SSS, but not the PAS, suggesting that phonatory function
is related to the oropharyngeal swallowing function, but not directly to the
aspiration itself. CONCLUSION: The correlation between MPT and several swallowing
related elements was identified, indicating an interactive correlation between
swallowing and phonation. This result justifies voice therapy as a treatment for
dysphagia in patients with Parkinsonism.
PMID- 29961741
TI - The Availability of Quantitative Assessment of Pain Perception in Patients With
Diabetic Polyneuropathy.
AB - OBJECTIVE: To evaluate the usefulness of the quantitative assessment of pain
perception (QAPP) in diabetic polyneuropathy (DPN) patients. METHODS: Thirty-two
subjects with DPN were enrolled in this study. The subjects' pain perception was
assessed quantitatively. Current perception threshold (CPT) and pain equivalent
current (PEC) were recorded. All patients were tested with a nerve conduction
study (NCS) for evaluation of DPN and pain-related evoked potential (PREP) for
evaluation of small fiber neuropathy (SFN) on bilateral upper and lower limbs.
All patients were asked to participate in tests such as visual analogue scale
(VAS) and SF-36 Health Survey Version 2 to evaluate their subjective pain and
quality of life, respectively. RESULTS: The PEC of QAPP showed significant
correlations with VAS (p=0.002) and physical function surveyed with SF-36 Health
Survey Version 2 (p=0.035). The results of QAPP had no correlation with NCS, but
there was a significant relationship between the CPT of QAPP and PREP (p=0.003).
CONCLUSION: The QAPP may be useful not only in providing objective evaluations of
subjective pain in patients with DPN but also in the assessment of diabetic SFN.
PMID- 29961742
TI - The Changes of CTX, DPD, Osteocalcin, and Bone Mineral Density During the
Postmenopausal Period.
AB - OBJECTIVE: To investigate appropriate treatment time and useful bone turnover
markers (BTMs) for monitoring bone turnover during the postmenopausal period, we
analyzed changes of two bone resorption markers; serum carboxyterminal
telopeptide of collagen I (s-CTX), urine deoxypyridinoline (u-DPD), one bone
formation marker; serum osteocalcin (s-OC), and bone mineral density (BMD) in
Korean postmenopausal women. METHODS: Seventy-eight menopausal women were divided
into three groups according to postmenopausal period: group I (0-5 years), group
II (6-10 years), group III (>=10 years). All groups were subdivided into an
osteoporosis group (T-score<=-2.5) and a non-osteoporosis group (T-score>-2.5).
BTMs such as s-CTX, u-DPD, s-OC, and BMD (g/cm2) were measured by dual-energy X
ray absorptiometry (DXA) in all patients. Analysis of variables among groups
based on the postmenopausal period was performed using ANOVA. RESULTS: There was
significant negative correlation between BMD and postmenopausal period. The
levels of all BTMs including s-CTX, u-DPD, and s-OC were highest in group II and
the increased levels of all BTMs subsequently declined in group III. The levels
of BTMs were higher in the osteoporosis groups than in the non-osteoporosis
groups in all subjects. It was statistically significant that the level of s-CTX
in group I was higher in the osteoporosis group than in the non-osteoporosis
group. CONCLUSION: This study showed that bone resorption and bone formation were
the highest 5-10 years after menopause, and s-CTX is more useful than u-DPD among
the bone resorption markers. It's important to measure serially both BMD and BTM
within 10 years after menopause for accurate diagnosis and management for
postmenopausal osteoporosis.
PMID- 29961743
TI - Clinical and Radiological Evaluation After Chemical Synovectomy With Rifampicin
in Hemophilic Arthropathy: Korean Experience With a 2-Week Interval Protocol.
AB - OBJECTIVE: To assess the clinical outcome of chemical synovectomy with rifampicin
in hemophilic arthropathy by using the World Federation of Hemophilia (WFH)
scoring system and plain radiograph. METHODS: We performed rifampicin synovectomy
(RS) on 30 joints of 28 hemophilic patients diagnosed as hemophilic arthropathy
stage I-III (based on Fernandez-Palazzi clinical classification). Clinical status
(bleeding frequency, pain, joint physical status) and radiological staging were
evaluated as parts of the WFH scoring system before and 1 year after RS. The
patients were divided into two groups by the Arnold-Hilgartner scale of the
initial X-ray as stage 3 or less for the low-stage group (n=17) and over 3 for
the high-stage group (n=13). RESULTS: Total WFH joint physical scores were
reduced after injection, and the number of bleeding episodes and pain showed
especially significant improvement. For other subscores of the WFH joint physical
score, only swelling, range of motion, and crepitus showed statistically
significant improvement. According to the severity of the radiologic finding, the
WFH joint physical score of both the low-stage and high-stage groups showed
significant improvement. In the radiological aspect, the low-stage group, without
joint space narrowing at the initial plain radiograph, showed no further
aggravation after injection. However, in the high-stage group, radiology found
aggravation regardless of the procedure. CONCLUSION: It is suggested that
chemical synovectomy with rifampicin may prevent hemarthrosis and improve
clinical symptoms. Especially in the early stage of arthropathy without joint
space narrowing, it seems to have an additional benefit that delays radiological
aggravation and preserves joint status.
PMID- 29961744
TI - Motor and Sensory Function as a Predictor of Respiratory Function Associated With
Ventilator Weaning After High Cervical Cord Injury.
AB - OBJECTIVE: To analyze the respiratory function of high cervical cord injury
according to ventilator dependence and to examine the correlations between
diaphragm movement found on fluoroscopy and sensory and motor functions. METHODS:
A total of 67 patients with high cervical spinal cord injury (SCI), admitted to
our hospital were enrolled in the study. One rehabilitation physician performed
sensory and motor examinations on all patients while each patient was in the
supine position on the American Spinal Injury Association (ASIA) standard. In
addition, fluoroscopic diaphragm movement studies and bedside spirometry were
performed. RESULTS: Bedside spirometry and diaphragm fluoroscopic tests were
analyzed according to ventilator dependence. Forced vital capacity and maximal
inspiratory pressure were significantly higher in the ventilator weaned group.
Natural breathing during the fluoroscopic diaphragm examinations and ventilator
weaning showed statistical significance with the movement on the right, while
deep breathing showed statistical significance with the movement on both sides.
Deep breathing movement has correlation with the C5 key muscle. Diaphragm
movement has correlation with right C3 and bilateral C4 sensory functions.
CONCLUSION: The present expansion study showed that, through simple bedside
physical examinations, rehabilitation physicians could relatively easily predict
diaphragm movement and respiratory function recovery, which showed significance
with ventilator weaning in patients with high cervical SCI.
PMID- 29961745
TI - Needs for Medical and Rehabilitation Services in Adults With Cerebral Palsy in
Korea.
AB - OBJECTIVE: To investigate medical comorbidities and needs for medical and
rehabilitation services of adults with cerebral palsy (CP) in Korea. METHODS:
This was a prospective cross-sectional study. One hundred fifty-four adults with
CP were enrolled in the study between February 2014 and December 2014.
Information was obtained from participants regarding functional status,
demographic and socioeconomic data, medical problems, and requirements for and
utilization of medical and rehabilitation services. RESULTS: The participants
included 93 males and 61 females with a mean age of 40.18+/-9.15 years. The
medical check-up rate of adults with CP was lower than that of healthy adults and
the total population with disabilities (53.2% vs. 58.6% vs. 70.4%). A quarter of
the subjects failed to visit the hospital during the past year, and the main
reason was the financial burden. Due to a cost burden and lack of knowledge, more
than one-third of the subjects had unmet needs for rehabilitation services; the
majority reported needs for rehabilitation services, such as physical therapy for
pain management. CONCLUSION: The medical check-up rate was lower in the adults
with CP, even though their medical comorbidities were not less than those of
healthy people. Several non-medical reasons hindered them from receiving proper
medical and rehabilitation services. Such barriers should be managed effectively.
PMID- 29961746
TI - Optimal Placement of Needle Electromyography in Extensor Indicis: A Cadaveric
Study.
AB - OBJECTIVE: To identify the center of extensor indicis (EI) muscle through cadaver
dissection and compare the accuracy of different techniques for needle
electromyography (EMG) electrode insertion. METHODS: Eighteen upper limbs of 10
adult cadavers were dissected. The center of trigonal EI muscle was defined as
the point where the three medians of the triangle intersect. Three different
needle electrode insertion techniques were introduced: M1, 2.5 cm above the lower
border of ulnar styloid process (USP), lateral aspect of the ulna; M2, 2 finger
breadths (FB) proximal to USP, lateral aspect of the ulna; and M3, distal fourth
of the forearm, lateral aspect of the ulna. The distance from USP to the center
(X) parallel to the line between radial head to USP, and from medial border of
ulna to the center (Y) were measured. The distances between 3 different points
(M1- M3) and the center were measured (marked as D1, D2, and D3, respectively).
RESULTS: The median value of X was 48.3 mm and that of Y was 7.2 mm. The median
values of D1, D2 and D3 were 23.3 mm, 13.3 mm and 9.0 mm, respectively.
CONCLUSION: The center of EI muscle is located approximately 4.8 cm proximal to
USP level and 7.2 mm lateral to the medial border of the ulna. Among the three
methods, the technique placing the needle electrode at distal fourth of the
forearm and lateral to the radial side of the ulna bone (M3) is the most accurate
and closest to the center of the EI muscle.
PMID- 29961747
TI - Factors Associated With Discharge Destination in Advanced Cancer Patients With
Bone Metastasis in a Japanese Hospital.
AB - OBJECTIVE: To analyze patient characteristics of cancer rehabilitation and
outcomes at our hospital. METHODS: This retrospective study analyzed 580
patients, who underwent cancer rehabilitation at our hospital and rehabilitation
outcome after therapy were investigated. The relationship between the initial
Barthel index and discharge outcomes was investigated, with a special focus on
cancer patients with bone metastasis. The Barthel index and performance status
(Eastern Cooperative Oncology Group) before and after rehabilitation were
analyzed, and threshold value of home discharge was calculated from a receiver
operating characteristic curve (ROC). General criteria for home discharge from
our hospital included independence in performing basic activities of daily living
such as bathing, feeding, and toileting or availability of home support from a
family member/caregiver. RESULTS: The outcomes after rehabilitation among all the
patients were as follows: discharge home 59%, death 13%, and others 27%.
Statistical differences were observed between the initial and final values of the
Barthel index in patients with bone metastasis, who could be discharged home
(p=0.012). ROC analysis of the initial Barthel index for predicting home
discharge revealed a threshold value of 60, sensitivity of 0.76, and specificity
of 0.72. CONCLUSION: The patients with bone metastasis had a lower rate of home
discharge and a higher rate of mortality than all the study patients who
underwent cancer rehabilitation at our hospital. It is proposed that at the time
of initiation of rehabilitation for patients with bone metastasis, an initial
Barthel index lower than 60 might predict a worse outcome than home discharge.
PMID- 29961748
TI - Diagnosis of Pure Ulnar Sensory Neuropathy Around the Hypothenar Area Using
Orthodromic Inching Sensory Nerve Conduction Study: A Case Report.
AB - Ulnar neuropathy at the wrist is an uncommon disease and pure ulnar sensory
neuropathy at the wrist is even rarer. It is difficult to diagnose pure ulnar
sensory neuropathy at the wrist by conventional methods. We report a case of pure
ulnar sensory neuropathy at the hypothenar area. The lesion was localized between
3 cm and 5 cm distal to pisiform using orthodromic inching test of ulnar sensory
nerve to stimulate at three points around the hypothenar area. Ultrasonographic
examination confirmed compression of superficial sensory branch of the ulnar
nerve. Further, surgical exploration reconfirmed compression of the ulnar nerve.
This case report demonstrates the utility of orthodromic ulnar sensory inching
test.
PMID- 29961749
TI - Femoral Neuropathy Secondary to Autosomal Dominant Polycystic Kidney Disease: A
Case Report.
AB - Compressive femoral neuropathy is a disabling condition accompanied by difficulty
in hip flexion and knee extension. It may result from retroperitoneal hematoma or
bleeding, or from complications associated with pelvic, hip surgery, and renal
transplants. A 55-year-old female with autosomal dominant polycystic kidney
disease presented with proximal muscle weakness in lower extremities. The patient
experienced recurrent renal cyst infection, with aggravated weakness during each
event. Electromyography and nerve conduction study revealed bilateral femoral
neuropathy. Computed tomography and magnetic resonance images were added to
further identify the cause. As a result, a diagnosis of femoral neuropathy caused
by enlarged polycystic kidney was made. Cyst infection was managed with
antibiotics. Renal function was maintained by frequent regular hemodialysis.
While avoiding activities that may increase abdominal pressure, rehabilitation
exercises were provided. Motor strength in hip flexion and knee extension
improved, and was confirmed via electrodiagnostic studies.
PMID- 29961750
TI - A Challenging Case of Retroperitoneal Abscess in a Post-Partum Crohn's Disease
Patient.
AB - BACKGROUND Crohn's disease (CD) is an inflammatory bowel disease affecting
approximately 1 in 3000 people in the United States. Since the inflammation of CD
is transmural, patients are at risk for fistula and abscess formation.
Retroperitoneal abscesses are one type of which physicians must be aware. CASE
REPORT We present the case of a 29-year-old woman with CD who complained of right
hip and flank pain that began when she was 6-months pregnant. After delivery, she
continued to complain of severe right flank pain and was admitted to the hospital
1 month later. CT scan imaging revealed a complicated retroperitoneal and right
flank abscess, possibly due to a colonic intramural fistula. She developed severe
acute necrotizing soft-tissue infection requiring 13 days of intensive care. She
required debridement of the necrotizing infection of the right flank, drainage of
the abscess, and washout for intraperitoneal sepsis. The patient tolerated the
procedures well and was discharged 1 month later. CONCLUSIONS Given that the
clinical manifestation of retroperitoneal fistula with abscess is insidious and
its formation is less common than intraperitoneal abscesses, we hope healthcare
providers learn from this case to avoid morbidity and mortality. When presented
with a pregnant CD patient complaining of nonspecific abdominal symptoms,
providers should consider fistulization and/or abscess formation. The option to
evaluate pregnant patients using noninvasive methods, such as ultrasound or low
dose CT scan, can decrease radiation exposure to the fetus and prevent delays in
diagnosis and treatment.
PMID- 29961751
TI - Effects of 3-Tetrazolyl Methyl-3-Hydroxy-Oxindole Hybrid (THOH) on Cell
Proliferation, Apoptosis, and G2/M Cell Cycle Arrest Occurs by Targeting Platelet
Derived Growth Factor D (PDGF-D) and the MEK/ERK Signaling Pathway in Human Lung
Cell Lines SK-LU-1, A549, and A-427.
AB - BACKGROUND The aim of this study was to evaluate the effects of 3-tetrazolyl
methyl-3-hydroxy-oxindole hybrid (THOH) on cell proliferation, apoptosis, and the
cell cycle in human lung cancer cell lines SK-LU-1, A549, and A-427, and the
normal lung fibroblast cell line, MRC-5, in vitro. MATERIAL AND METHODS Human
lung adenocarcinoma cells SK-LU-1, A549, and A-427, and the normal lung
fibroblast cells, MRC-5 were cultured and treated with increasing concentrations
of 10 mM of a stock solution of THOH in dimethyl sulfoxide (DMSO). An MTT cell
proliferation assay was used. Cell apoptosis and the cell cycle were studied
using fluorescence-activated cell sorting (FACs) with fluorescein isothiocyanate
(FITC), Annexin-V, propidium iodide (PI), and nuclear staining with 4',6
diamidino-2-phenylindole (DAPI). DNA damage was measured using the comet (single
cell gel electrophoresis) assay. Cell migration was evaluated using a wound
healing assay, and Western blotting was used to measure protein expression
levels. RESULTS Treatment of SK-LU-1 cells with THOH inhibited cell migration.
Treatment of lung cancer cells, SK-LU-1, A549, and A-427, with THOH inhibited
cell proliferation, with the most marked inhibition found in the SK-LU-1 lung
cancer cells (IC50, 12 uM). Treatment of lung cancer cells, SK-LU-1, A549, and A
427, with THOH increased cell apoptosis, resulted in G2/M cell cycle arrest, and
inhibited both the platelet-derived growth factor D (PDGF-D) and MEK/ERK
signaling pathways. CONCLUSIONS Treatment of adenocarcinoma cells, SK-LU-1, A549,
and A-427, with THOH inhibited cell proliferation, apoptosis, and resulted in
G2/M cell cycle arrest by targeting PDGF-D and the MEK/ERK signaling pathway.
PMID- 29961752
TI - [Risk sharing contracts in the national health care system: Perceptions of health
care professionals].
AB - OBJECTIVE: Risk-sharing contracts (RSC) present a novel management tool, which
link the payment to the pharmaceutical company to health outcomes. The objective
of this work was to know the perception of health professionals about the utility
of these agreements in the Spanish National Health System. METHODS: A
questionnaire was designed to conduct a series of semi-structured interviews with
hospital pharmacy, laboratory and oncology professionals from Spanish hospitals
in Madrid, Aragon, Castilla-La Mancha, Castilla y Leon, Cataluna, La Rioja, Pais
Vasco and Navarra. The selection criteria was for convenience. The interview
period was from April to November 2017. A qualitative analysis was performed
based on the responses from 14 interviews. RESULTS: All the surveyed affirmed
that the CRCs allow to improve the economic and administrative management of the
hospital, emphasizing as main advantages the budgetary control, the obtaining of
funding and the savings possibilities. CRCs are perceived (13 of 14 respondents)
as agreements with positive health implications because they increased the
portfolio of treatments and had greater efficacy. The need for CRCs to register
patients, involved monitoring and control, also contributed to the improvement of
their health. In addition, CRCs were believed (8 out of 14 respondents) to
facilitate the introduction of personalized medicine (MP) as both depend on
diagnostic tests, one for screening reasons (MP) and the other for obtain
clinical evidences that improve economic outcomes (CRC). However, it was
considered that signing the CRCs entails the need to modify certain regulations
(5 out of 14 respondents) as well as to increase the number of staff to handle
bureaucratic tasks and to increase laboratory tests, which can complicate health
management. CONCLUSIONS: Qualitative social research techniques have proven to be
useful for gathering information on a new topic and understanding the perception
of the advantages and disadvantages of CRCs, as well as their association with
the MP. In addition, synergies were detected between the CRCs and the MP.
Respondents had positive opinions on CRCs about its application, although work
must be done in order to improve the normative and organizational context so that
the additional complexity that they incorporate does not constitute an obstacle
to extend its use.
PMID- 29961753
TI - CRISPR/Cas9-mediated deletion of miR-146a enhances antiviral response in HIV-1
infected cells.
AB - The human immunodeficiency virus type 1 (HIV-1) causes persistent infection in
human and induces miR-146a expression in infected cells. miR-146a represses the
innate immune response by inhibiting the expression of TRAF6 and IRAK1 genes,
thus negatively controls the NF-kappaB-related cytokines and interferon
stimulated genes. Here we reported that lentiviral CRISPR/Cas9 system was highly
efficient in introducing mutations in the precursor miR-146a genomic sequences,
resulting in a loss of miR-146a expression and function. miR-146a ablation led to
increasing cytokines production in LPS-stimulated A549 cells. Moreover, miR-146a
knockout in HIV-1 infected MT2 cells markedly increased the expression of
cytokines and HIV-1 restriction factors and reversed T cell exhaustion markers
expression, thus influencing HIV-1 replication. Our study indicates that
lentiviral CRISPR/Cas9-mediated gene editing is an effective approach to abrogate
miR-146a expression, which consequently inhibits HIV-1 replication as well as
proviral reactivation by enhancing the expression of cytokines and HIV-1
restriction factors.
PMID- 29961754
TI - Autophagy-related gene LC3 expression in tumor and liver microenvironments
significantly predicts recurrence of hepatocellular carcinoma after surgical
resection.
AB - BACKGROUND: The role of autophagy-related markers as the prognostic factor of
post-operative hepatocellular carcinoma (HCC) recurrence remained controversial.
METHODS: Overall, 535 consecutive HCC patients undergoing curative resection from
2010 to 2014 were followed and classified with early (ER, <2 years) or late
recurrence (LR). Autophagy-related markers, LC3, Beclin-1, and p62 expression was
immunohistochemically assessed in HCC and adjacent non-tumor (ANT) tissues.
RESULTS: HCC recurred in 245 patients: 116 with ER and 129 with LR. The
cumulative incidence of recurrence at 1, 3, 5, and 7 years was 9.7%, 33.9%,
53.3%, and 66.3%, respectively. In multivariate analysis, HCC recurrence was
significantly associated with low LC3 expression in tumor and ANT tissues, HCC
tissues only and ANT tissues only (hazard ratio/95% confidence interval:
6.12/2.473-17.53, 4.18/1.285-13.61, and 1.89/1.299-2.757) and macrovascular
invasion (1.63/1.043-2.492) and cirrhosis (1.59/1.088-2.326). ER was
significantly associated with low LC3 expression in tumor and ANT tissues, HCC
tissues only and ANT tissues only (6.54/2.934-15.81, 3.26/1.034-10.27, and
2.09/1.313-3.321) and macrovascular and microvascular invasion (2.65/1.306-5.343
and 2.55/1.177-5.504). LR was significantly associated with low LC3 expression in
tumor and ANT tissues, HCC tissues only and ANT tissues only (5.02/1.372-18.83,
3.19/1.13-12.09, and 1.66/1.051-2.620) and cirrhosis (1.66/1.049-2.631). Patients
with low and high LC3 expression in tumor and ANT tissues showed a 5-year
cumulative recurrence of 94.3% and 41.7%, respectively (p < 0.001). CONCLUSIONS:
The high LC3 expression in the tumor and liver microenvironments is significantly
associated with lower HCC recurrence. Furthermore, tumor characteristics and
liver microenvironment were also significantly associated with ER and LR,
respectively. TRANSLATIONAL IMPACT: The analysis for LC3 expression in both the
HCC and ANT tissues could identify patients at risk of HCC recurrence.
PMID- 29961755
TI - Role of age in presentation, response to therapy and outcome of autoimmune
hepatitis.
AB - BACKGROUND: Few studies with diverging results and a small sample size have
compared autoimmune hepatitis (AIH) in the elderly to younger patients. AIM: To
unbiasedly investigate the role of age in behaviour and treatment outcome of AIH.
METHODS: All patients with probable or definite AIH type 1 in four tertiary
academic centres were included in this retrospective-and since 2006 prospective
cohort study. Influence of age on presentation, remission and outcome of AIH were
investigated. RESULTS: 359 patients were included. Presence of cirrhosis at AIH
diagnosis around 30% was independent of age. ALAT was higher at age 30-60 years
on AIH diagnosis, and above age 60 there were less acute onset, less jaundice and
more concurrent autoimmune disease. Remission was reached in 80.2%, incomplete
remission in 18.7%, only 1.1% (all aged 50-65) was treatment-refractory. Age was
not an independent predictor of remission, while cirrhosis was. Above age 45
there was more diabetes, above age 60 more loss of remission. Rate of progression
to cirrhosis was 10% in the 10 years after diagnosis and unrelated to age at AIH
diagnosis. With onset below age 30, there was more development of decompensated
cirrhosis over time. With higher age at AIH diagnosis there was a lower survival
free of liver-related death or liver transplantation. CONCLUSIONS: AIH presents
at all ages. Age influences features at diagnosis, but not response to treatment,
while survival without liver-related death or liver transplantation decreases
with higher age at diagnosis.
PMID- 29961756
TI - Isolated limb perfusion for unresectable extremity cutaneous squamous cell
carcinoma; an effective limb saving strategy.
AB - BACKGROUND: A small minority of patients present with locally advanced cutaneous
Squamous Cell Carcinoma (cSCC). The aim of this study was to evaluate the
effectiveness of Tumour necrosis factor alpha (TNF) and melphalan based isolated
limb perfusion (TM-ILP) as a limb saving strategy for locally advanced extremity
cSCC. METHODS: A retrospective search from prospectively maintained databases, at
two tertiary referral centers, was performed to identify patients treated with TM
ILP for locally advanced cSSC of an extremity between 2000 and 2015. RESULTS: A
total of 30 patients treated with TM-ILP for cSCC were identified, with a median
age of 71 years (36-92) and 50% female. Response could not be evaluated in 3
patients. After a median follow up of 25 months, the overall response rate was
81% (n = 22), with 16 patients having a complete response (CR, 59%). A total of 7
patients developed local recurrence, with a median time to recurrence of 9 months
(Interquartile Range 7-10). Progressive disease was observed in 5 patients (19%).
Limb salvage rate was 80%. The overall 2-year survival was 67%. CONCLUSIONS: TM
ILP should be considered as an option in patients with locally advanced cSCC in
specialised centers, resulting in a high limb salvage rate.
PMID- 29961757
TI - Reply to 'Comment on 'Dairy, calcium, vitamin D and ovarian cancer risk in
African-American women''.
PMID- 29961758
TI - Comment on 'Dairy, calcium, vitamin D, and ovarian cancer risk in African
American women'.
PMID- 29961759
TI - Early metabolic response in sequential FDG-PET/CT under cetuximab is a predictive
marker for clinical response in first-line metastatic colorectal cancer patients:
results of the phase II REMOTUX trial.
AB - BACKGROUND: To assess the predictive value of early metabolic response (DeltaSUV)
after short-term treatment with first-line cetuximab in patients (pts) with RAS
wt metastatic colorectal cancer (mCRC). METHODS: In this prospective phase II
study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2
weeks. DeltaSUV was assessed with FDG-PET/CT on days 0 and 14. Early clinical
response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI
cetuximab. Primary endpoint was the predictive significance of DeltaSUV for ECR.
Secondary endpoints were PFS (progression free survival), OS and the influence of
DeltaSUV on survival. RESULTS: Forty pts were enroled and 33 pts were evaluable
for the primary endpoint. The CT response rate was 57.6%. For responders,
DeltaSUV was significantly higher (p = 0.0092). A significant association of
DeltaSUV with ECR was found (p = 0.02). Median PFS was 11.7 months and median OS
was 33.5 months with a 1-year survival rate of 87.9%. DeltaSUV was found to
significantly impact the hazard for OS (p = 0.045). CONCLUSIONS: We demonstrate
that cetuximab induces metabolic responses in mCRC pts. The study endpoint was
met with the DeltaSUV discriminating between responders and non-responders.
However, these data should be validated in larger patient cohorts.
PMID- 29961760
TI - Patients with early-stage oropharyngeal cancer can be identified with label-free
serum proteomics.
AB - BACKGROUND: The increasing incidence of oropharyngeal squamous cell carcinoma
(OPSCC) is mainly related to human papillomavirus (HPV) infection. As OPSCCs are
often diagnosed at an advanced stage, mortality and morbidity remain high. There
are no diagnostic biomarkers for early detection of OPSCC. METHODS: Serum from 25
patients with stage I-II OPSCC, and 12 healthy controls, was studied with
quantitative label-free proteomics using ultra-definition MSE. Statistical
analyses were performed to identify the proteins most reliably distinguishing
early-stage OPSCCs from controls. P16 was used as a surrogate marker for HPV. P16
positive and P16-negative tumours were analysed separately. RESULTS: With two or
more unique proteins per identification, 176 proteins were quantified. A clear
separation between patients with early-stage tumours and controls was seen in
principal component analysis. Latent structures discriminant analysis identified
96 proteins, most reliably differentiating OPSCC patients from controls, with 13
upregulated and 83 downregulated proteins in study cases. The set of proteins was
studied further with network, pathway and protein-protein interaction analyses,
and found to participate in lipid metabolism, for example. CONCLUSIONS: We found
a set of serum proteins distinguishing early-stage OPSCC from healthy
individuals, and suggest a protein set for further evaluation as a diagnostic
biomarker panel for OPSCC.
PMID- 29961761
TI - Epithelial cell adhesion efficacy of a novel peptide identified by panning on a
smooth titanium surface.
AB - Epithelial attachment via the basal lamina on the tooth surface provides an
important structural defence mechanism against bacterial invasion in combating
periodontal disease. However, when considering dental implants, strong epithelial
attachment does not exist throughout the titanium-soft tissue interface, making
soft tissues more susceptible to peri-implant disease. This study introduced a
novel synthetic peptide (A10) to enhance epithelial attachment. A10 was
identified from a bacterial peptide display library and synthesized. A10 and
protease-activated receptor 4-activating peptide (PAR4-AP, positive control) were
immobilized on commercially pure titanium. The peptide-treated titanium showed
high epithelial cell migration ability during incubation in platelet-rich plasma.
We confirmed the development of dense and expanded BL (stained by Ln5) with
pericellular junctions (stained by ZO1) on the peptide-treated titanium surface.
In an adhesion assay of epithelial cells on A10-treated titanium, PAR4-AP-treated
titanium, bovine root and non-treated titanium, A10-treated titanium and PAR4-AP
treated titanium showed significantly stronger adhesion than non-treated
titanium. PAR4-AP-treated titanium showed significantly higher inflammatory
cytokine release than non-treated titanium. There was no significant difference
in inflammatory cytokine release between A10-treated and non-treated titanium.
These results indicated that A10 could induce the adhesion and migration of
epithelial cells with low inflammatory cytokine release. This novel peptide has a
potentially useful application that could improve clinical outcomes with titanium
implants and abutments by reducing or preventing peri-implant disease.
PMID- 29961762
TI - Differences in prenatal aneuploidy screening among African-American women with
hemoglobin S variants.
AB - OBJECTIVE: It has been shown that hemoglobinopathies increase the risk of
pregnancy complications and placental dysfunction. This could alter the placental
analytes examined during prenatal aneuploidy screening. Our objective was to
determine whether there is a difference in maternal serum screening results for
women with hemoglobin S variants (AS, SS, SC, S/beta thalassemia) compared with
women with normal hemoglobin (AA). STUDY DESIGN: This is a retrospective cohort
study in African-American women receiving aneuploidy screening at MedStar
Washington Hospital Center from 2008 to 2015. We evaluated 79 women with
hemoglobin S variants (69 AS and 10 sickle cell disease (SCD)) and 79 controls.
Descriptive statistics (means, medians, and frequencies) were calculated for each
group. For the continuous variables, differences in the averages between the two
groups were tested using the t test or Wilcoxon rank sum test. Differences in the
averages between three or more groups were tested using the analysis of variance
test or the Kruskal-Wallis test. RESULTS: Demographics were similar between cases
and controls. The overall screen positive rate for Down syndrome among patients
with sickle cell trait (AS) was 3% (2/69). For patients with SCD, the overall
screen positive rate was 10% (1/10). None of the women in the control population
(AA) has a positive Down syndrome screening result (0/79). CONCLUSION: As
expected, the screen positive rate in patients with hemoglobin S variants was
higher than controls, however, patients with sickle cell trait do not appear to
be at an increased risk for false-positive results with serum aneuploidy
screening compared with the general population. We did, however, find an
increased risk of false-positive quad screen results in patients with sickle cell
disease.
PMID- 29961763
TI - Non-contact retinal imaging compared to indirect ophthalmoscopy for retinopathy
of prematurity screening: infant safety profile.
AB - OBJECTIVE: Most retinopathy of prematurity screening involves an ophthalmologist
performing indirect ophthalmoscopy, which can be stressful to infants. The
purpose of this study is to evaluate the safety profile (using cardiopulmonary
events as an indicator) of imaging infants with a non-contact retinal camera
compared to examining them using indirect ophthalmoscopy. STUDY DESIGN:
Prospective cohort study of 99 infants at a community hospital who were examined
using indirect ophthalmoscopy and imaged using a non-contact retinal camera for
retinopathy of prematurity. We evaluated the difference in the occurrence of
safety events (i.e., clinically significant bradycardia, tachycardia, oxygen
desaturation, or apnea) following the clinical examination versus retinal
imaging. RESULT: Safety events occurred after 0.8% (n = 1) of imaging sessions
and 5.8% (n = 18) of clinical examinations (mean difference = -0.055 (p = 0.015),
favoring imaging). CONCLUSION: Retinal imaging with a non-contact camera was well
tolerated and less stressful to infants compared to indirect ophthalmoscopy by an
ophthalmologist.
PMID- 29961764
TI - Photoplethysmographic assessment of pulse transit time correlates with
echocardiographic measurement of stroke volume in preterm infants with patent
ductus arteriosus.
AB - OBJECTIVE: We aimed to correlate photoplethysmographic parameters with stroke
volume in infants with PDA. Photoplethysmography constitutes the optical signal
in pulse oximetry. STUDY DESIGN: Stroke volume was determined
echocardiographically. Pulse transit time, right hand to foot arrival time
difference, and relative amplitude were measured from pulse oximeter and ECG
waveforms. Photoplethysmographic parameters before and after PDA closure were
compared with stroke volume. RESULTS: After PDA closure, pulse transit time to
the hand and to the foot were prolonged (54.7 +/- 6.7 vs 65.5 +/- 9.8 ms, p <
0.001, 82.5 +/- 12.8 vs 88.6 +/- 10.6 ms, p = 0.03), arrival time difference
decreased (27.7 +/- 7.6 vs 23.1 +/- 5.6 ms, p = 0.021), and relative amplitude
decreased (from 2.1 +/- 0.7% to 1.5 +/- 0.5%, p = 0.003). The time-based
photoplethysmographic parameters correlated with stroke volume. CONCLUSIONS:
Photoplethysmographic waveform parameters are significantly different before and
after PDA closure and the time-based parameters correlate well with stroke
volume. Monitoring pulse transit time may assist in evaluation for spontaneous
PDA closure or response to therapy.
PMID- 29961765
TI - Raspberry alleviates obesity-induced inflammation and insulin resistance in
skeletal muscle through activation of AMP-activated protein kinase (AMPK) alpha1.
AB - OBJECTIVE: Through dynamic means, etiological factors, including chronic
inflammation and insulin resistance have the potential to perpetuate metabolic
incidences such as type 2 diabetes and obesity. Abatement of such syndromes can
be achieved by complex mechanisms initiated through bioactive compounds such as
polyphenols derived from fruits. Using a whole-fruit approach, the effects of
dietary red raspberry, which is rich in polyphenols, on inflammatory responses
and insulin resistance in the skeletal muscles of Mus musculus were studied along
with the potential role of AMP-activated protein kinase (AMPK) to act as a key
mediator. SUBJECTS: Wild-type (WT) mice and mice deficient in the catalytic
subunit (alpha1) of AMPK (AMPKalpha1-/-) were fed with a high-fat diet (HFD) or
HFD supplemented with raspberry (5% dry weight) for 10 weeks. Factors involved in
inflammatory responses, insulin signaling transduction, and mitochondrial
biogenesis were evaluated. RESULTS: Dietary raspberry reduced ectopic lipid
storage, alleviated inflammation responses, improved whole-body insulin
sensitivity, and promoted mitochondrial biogenesis in the skeletal muscle of WT
mice, but not AMPKalpha1-/- mice. CONCLUSIONS: AMPKalpha1 is an important
mediator for the beneficial effects of raspberry through alleviating inflammatory
responses and sensitizing insulin signaling in skeletal muscle of HFD-fed mice.
PMID- 29961766
TI - Beyond the panel: preconception screening in consanguineous couples using the
TruSight One "clinical exome".
AB - PURPOSE: To provide proof of concept by broadening preconception screening beyond
targeted testing to inform reproductive risk in consanguineous couples. METHODS:
Consanguineous couples were screened for autosomal recessive and X-linked
disorders using the TruSight One panel of 4,813 genes associated with human
disease. RESULTS: We recruited 22 couples, of whom 15 elected to have sequencing.
We found four couples to be at risk of autosomal recessive disorders, including
one with a child affected by Poretti-Boltshauser syndrome (a diagnosis not made
prior to the study) and another previously known to carry a beta-globin variant.
Two couples were found to carry variants unrelated to known family history. These
variants were in the genes C5orf42 (associated with Joubert syndrome and
orofaciodigital syndrome) and GYS2 (associated with glycogen synthase
deficiency). One known variant was not detected-a single exon deletion in FAM20C.
We would not expect to identify this variant with the methodology employed. Of
the four variants identified, only the beta-globin variant would have been found
using available commercial preconception screening panels. CONCLUSION:
Preconception screening of consanguineous couples for recessive and X-linked
disorders using genomic sequencing is practicable, and is likely to detect many
more at-risk couples than any targeted panel could achieve. A couples-based
approach greatly reduces the associated analysis and counselling burden.
PMID- 29961767
TI - Genome sequencing as a first-line genetic test in familial dilated
cardiomyopathy.
AB - PURPOSE: We evaluated genome sequencing (GS) as an alternative to multigene panel
sequencing (PS) for genetic testing in dilated cardiomyopathy (DCM). METHODS:
Forty-two patients with familial DCM underwent PS and GS, and detection rates of
rare single-nucleotide variants and small insertions/deletions in panel genes
were compared. Loss-of-function variants in 406 cardiac-enriched genes were
evaluated, and an assessment of structural variation was performed. RESULTS: GS
provided broader and more uniform coverage than PS, with high concordance for
rare variant detection in panel genes. GS identified all PS-identified pathogenic
or likely pathogenic variants as well as two additional likely pathogenic
variants: one was missed by PS due to low coverage, the other was a known disease
causing variant in a gene not included on the panel. No loss-of-function variants
in the extended gene set met clinical criteria for pathogenicity. One BAG3
structural variant was classified as pathogenic. CONCLUSION: Our data support the
use of GS for genetic testing in DCM, with high variant detection accuracy and a
capacity to identify structural variants. GS provides an opportunity to go beyond
suites of established disease genes, but the incremental yield of clinically
actionable variants is limited by a paucity of genetic and functional evidence
for DCM association.
PMID- 29961770
TI - A Tale of Three Tails and a Cystic Lesion: A Rare Cause of Recurrent Acute
Pancreatitis.
PMID- 29961769
TI - Population genomics in South East Asia captures unexpectedly high carrier
frequency for treatable inherited disorders.
AB - PURPOSE: Genomic studies have demonstrated the necessity of ethnicity-specific
population data to ascertain variant pathogenicity for disease diagnosis and
treatment. This study examined the carrier prevalence of treatable inherited
disorders (TIDs), where early diagnosis of at-risk offspring can significantly
improve clinical outcomes. METHODS: Existing exome/ genome sequencing data of 831
Singaporeans were aggregated and examined for disease causing variants in 104
genes associated with 80 TIDs. RESULTS: Among the 831 Singaporean participants,
genomic variant filtering and analysis identified 1 in 18 individuals (6%) to be
carriers amongst one of 13 TIDs. Citrin deficiency and Wilson disease had the
highest carrier frequency of 1 in 41, and 1 in 103 individuals, respectively. The
pathogenic variants associated with citrin deficiency were 24 times more
prevalent in our local cohorts when compared to Western cohorts. CONCLUSION: This
study demonstrates the value of a population specific genomic database to
determine true disease prevalence and has enabled the discovery of carrier
frequencies of treatable genetic conditions specific to South East Asian
populations, which are currently underestimated in existing data sources. This
study framework can be adapted to other population groups and expanded to
multiple genetic conditions to inform health policies directing precision
medicine.
PMID- 29961768
TI - Germline cancer susceptibility gene variants, somatic second hits, and survival
outcomes in patients with resected pancreatic cancer.
AB - PURPOSE: Germline variants in double-strand DNA damage repair (dsDDR) genes
(e.g., BRCA1/2) predispose to pancreatic adenocarcinoma (PDAC) and may predict
sensitivity to platinum-based chemotherapy and poly(ADP) ribose polymerase (PARP)
inhibitors. We sought to determine the prevalence and significance of germline
cancer susceptibility gene variants in PDAC with paired somatic and survival
analyses. METHODS: Using a customized next-generation sequencing panel,
germline/somatic DNA was analyzed from 289 patients with resected PDAC
ascertained without preselection for high-risk features (e.g., young age,
personal/family history). All identified variants were assessed for
pathogenicity. Outcomes were analyzed using multivariable-adjusted Cox
proportional hazards regression. RESULTS: We found that 28/289 (9.7%; 95%
confidence interval [CI] 6.5-13.7%) patients carried pathogenic/likely pathogenic
germline variants, including 21 (7.3%) dsDDR gene variants (3 BRCA1, 4 BRCA2, 14
other dsDDR genes [ATM, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C]), 3 Lynch
syndrome, and 4 other genes (APC p.I1307K, CDKN2A, TP53). Somatic sequencing and
immunohistochemistry identified second hits in the tumor in 12/27 (44.4%)
patients with germline variants (1 failed sequencing). Compared with noncarriers,
patients with germline dsDDR gene variants had superior overall survival (hazard
ratio [HR] 0.54; 95% CI 0.30-0.99; P = 0.05). CONCLUSION: Nearly 10% of PDAC
patients harbor germline variants, although the majority lack somatic second
hits, the therapeutic significance of which warrants further study.
PMID- 29961771
TI - Continuous Anti-TNFalpha Use Throughout Pregnancy: Possible Complications For the
Mother But Not for the Fetus. A Retrospective Cohort on the French National
Health Insurance Database (EVASION).
AB - OBJECTIVES: Inflammatory bowel diseases (IBD) need long-term treatment, which can
influence pregnancies in young women. Uncontrolled IBD is associated with poor
pregnancy outcomes. Despite the labeling of Anti-tumor necrosis factor (TNF)
antibodies (anti-TNFalpha) which indicates that their use is not recommended
during pregnancy, anti-TNFalpha are increasingly being used during pregnancy and
may expose women and their fetuses to treatment-related complications. Existing
recommendations on the timing of treatment during pregnancy are inconsistent. We
aimed to assess the safety of anti-TNFalpha treatment in pregnant women with IBD,
and up to the first year of life for their children. METHODS: An exposed/non
exposed retrospective cohort was conducted on the French national health system
database SNIIRAM (Systeme National d'Information Inter-Regimes de l'Assurance
Maladie). All IBD women who became pregnant between 2011 and 2014 were included.
Women with concomitant diseases potentially treated with anti-TNFalpha were
excluded. Anti-TNFalpha exposure (infliximab, adalimumab, golimumab or
certolizumab pegol) during pregnancy was retrieved from the exhaustive
prescription database in SNIIRAM. The main judgment criterion was a composite
outcome of disease-, treatment- and pregnancy-related complications during
pregnancy for the mother, and infections during the first year of life for
children. RESULTS: We analyzed data from 11,275 pregnancies (8726 women with
IBD), among which 1457 (12.9%) pregnancies were exposed to anti-TNFalpha, mainly
infliximab or adalimumab, with 1313/7722 (17.0%) suffering from Crohn's disease
and 144/3553 (4.1%) from ulcerative colitis. After adjusting for disease
severity, steroid use, age, IBD type, and duration and concomitant 6
mercaptopurine use, anti-TNFalpha treatment was associated with a higher risk of
overall maternal complications (adjusted Odds Ratio (aOR) = 1.49; 95% confidence
interval (CI): 1.31-1.67) and infections (aOR = 1.31; 95% CI: 1.16-1.47).
Maintaining anti-TNFalpha after 24 weeks did not increase the risk of maternal
complication, but interrupting the anti-TNFalpha increased relapse risk. No
increased risk for infection was found in children (aOR = 0.89; 95% CI: 0.76
1.05) born to mother exposed to anti-TNFalpha during pregnancy. CONCLUSIONS: Anti
TNFalpha treatment during pregnancy increased the risk of maternal complications
compared to unexposed; however, discontinuation before week 24 increased the risk
of disease flare. There was no increased risk for children exposed to anti
TNFalpha up to 1 year of life.
PMID- 29961772
TI - EUS-Guided Biliary Drainage Versus ERCP for the Primary Palliation of Malignant
Biliary Obstruction: A Multicenter Randomized Clinical Trial.
AB - OBJECTIVES: The goal of the study was to determine whether endoscopic ultrasound
(EUS)-guided biliary drainage (EUS-BD) is comparable to conventional
transpapillary stenting with endoscopic retrograde cholangiopancreatography
(ERCP) in palliation of malignant distal biliary obstruction. Although ERCP for
the palliation of malignant biliary obstruction is the standard of care, post
procedure pancreatitis and stent dysfunctions are not uncommon. While EUS-BD has
garnered interest as a viable alternative when ERCP is impossible, its role as a
primary palliation of malignant distal biliary obstruction is yet to be proven.
METHODS: We performed random allocation to EUS-BD or ERCP in 125 patients with
unresectable malignant distal biliary obstruction at four tertiary academic
referral centers in South Korea. RESULTS: Technical success rates were 93.8%
(60/64) for EUS-BD and 90.2% (55/61) for ERCP (difference 3.6%, 95% 1-sided
confidence interval lower limit -4.4%, P = 0.003 for noninferiority margin of
10%). Clinical success rates were 90.0% (54/60) in EUS-BD and 94.5% (52/55) in
ERCP (P = 0.49). Lower rates of overall adverse events (6.3% vs 19.7%, P = 0.03)
including post-procedure pancreatitis (0 vs 14.8%), reintervention (15.6% vs
42.6%), and higher rate of stent patency (85.1% vs 48.9%) were observed with EUS
BD. EUS-BD was also associated with more preserved quality of life (QOL) than
transpapillary stenting after 12 weeks of the procedure. CONCLUSIONS: This study
demonstrated comparable technical and clinical success rates between EUS-BD and
ERCP in relief malignant distal biliary obstruction. Substantially longer
duration of patency coupled with lower rates of adverse events and
reintervention, and more preserved QOL were observed with EUS-BD (cris.nih.go.kr,
Identifier: KCT0001396,
https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=9716<ype=&rtyp
= ).
PMID- 29961773
TI - Corrigendum: Computer-assisted quantification of motile and invasive capabilities
of cancer cells.
AB - This corrects the article DOI: 10.1038/srep15338.
PMID- 29961774
TI - Microporous 2D indium metal-organic frameworks for selective CO2 capture and
their application in the catalytic CO2-cycloaddition of epoxides.
AB - Four new 2D indium metal-organic frameworks (MOFs) (Me2NH2)[In(SBA)2] (1),
(Me2NH2)[In(SBA)(BDC)] (2), (Me2NH2)[In(SBA)(BDC-NH2)] (3), and
(NH4)3[In3Cl2(BPDC)5] (4), (H2SBA = 4,4'-sulfonyldibenzoic acid; H2BDC = 1,4
benzenedicarboxylic acid; H2BDC-NH2 = 2-amino-1,4-benzenedicarboxylic acid;
H2BPDC = 4,4'-biphenyldicarboxylic acid) have been synthesized under solvothermal
reaction conditions for compounds 1 to 3 and the DES (deep eutectic solvent)
reaction has been attempted for compound 4. The structure of these MOFs has been
determined by using single crystal X-ray diffraction study and all of theses four
2D monolayer framework with porous properties. The N2 gas sorption measurements
indicated that Brunauer-Emmer-Teller (BET) and Langmuir surface areas of compound
1 are 207 and 301 m2 g-1, respectively, which is probably the first one having
substantial gas uptake properties in the entire 2D In-MOF family to date.
Furthermore, these new indium MOFs on the addition of n-Bu4NBr were active for
the cycloaddition of CO2 and propylene oxide, generating propylene carbonates in
high conversions under mild conditions. Particularly, the most active MOF 4 was
found to efficiently couple CO2 with a series of terminal epoxides to give the
corresponding cyclic organic carbonates with high selectivities.
PMID- 29961775
TI - Electronic structure and large second-order non-linear optical property of COT
derivatives - a theoretical exploration.
AB - A new strategy to design new molecules based on a fused hydrocarbon ring system
comprising a COT ring and two 5-membered rings has been proposed for the study of
second order NLO properties. The four charge transferring groups -NR2 (R = H, Li,
Na and K) in conjunction with a sufficient number of electron withdrawing groups
lead to significant variation of structural parameters and polarity. The charge
transfer characteristics can be strongly modulated by introducing calcium metal
atoms at suitable sites. Ca metal atoms end-capping the nitrogen ends of two
adjacent -CN groups lead to electride character while a Ca metal atom bonded
directly to the COT ring leads to greater charge transfer. The size of the alkali
metal atom has been found to have a dramatic effect on the enhancement of first
hyperpolarizability. The most significant electronic asymmetry induced by the
larger potassium metal atom strongly enhances the magnitude of first
hyperpolarizability. The variation of first hyperpolarizability has been
satisfactorily explained in terms of TD-CAMB3LYP calculated spectroscopic
parameters in light of the two-state model.
PMID- 29961776
TI - A new route to substituted furocoumarins via copper-catalyzed cyclization between
4-hydroxycoumarins and ketoximes.
AB - A new route to substituted furocoumarins via copper-catalyzed cyclization between
4-hydroxycoumarins and ketoximes was developed. CuBr2 exhibited higher activity
than other copper salts, affording the desired furocoumarins in high yields. The
transformation proceeded readily in the absence of stoichiometric external
oxidants. The significance of this synthetic strategy would be (1) the easily
available starting materials; (2) low cost catalyst CuBr2; and (3) being without
stoichiometric external oxidants. This protocol is complementary to previous
approaches in the synthesis of substituted furocoumarins.
PMID- 29961777
TI - Carbon-contacted single molecule electrical junctions.
AB - A fully metal-free molecular junction (MJ) has been built by using an
electrochemically etched carbon fibre STM tip as the top electrode and graphene
as the bottom electrode. The corresponding conductance values for 1,n
alkanediamine and 1,n-alkanedithiol (n = 2, 4, 6, 8 and 10) have been measured
using the STM-I(s) technique. The tunnelling decay constant of the alkanediamine
and alkanedithiol junctions with these carbon contacts is much lower than the
corresponding metal contacted junctions of 0.24 and 0.38 per -CH2 unit, but the
junction conductance with these carbon contacts is also lower. The carbon fibre
tip can be considered a good candidate as an electrode. Compared with a gold tip,
the carbon fibre tip leads to correspondingly lower molecular junction
conductance.
PMID- 29961779
TI - The complex global response to copper in the multicellular bacterium Myxococcus
xanthus.
AB - The complex copper response of the multicellular proteobacterium M. xanthus
includes structural genes similar to those described in other bacteria, such as
P1B-type ATPases, multicopper oxidases, and heavy metal efflux systems. However,
the two time-dependent expression profiles of the different copper systems are
unique. There are a number of genes responsible for an immediate response, whose
expression increases after the addition of copper, but rapidly decreases
thereafter to basal levels. The regulatory element that controls this early
response is CorE, a novel extracytoplasmic function sigma factor that is
activated by Cu2+ and inactivated by Cu+. Other genes are part of a maintenance
response. These genes show a profile that slows up after the copper addition and
reaches a plateau at 24-48 h incubation. Most of the genes involved in this
response are encoded by the operon curA, which is regulated by the two-component
system CorSR. Moreover, other genes involved in the maintenance response are
regulated by different regulatory elements that remain unknown. Additionally,
copper activates the transcription of the structural genes for carotenoid
synthesis through a mechanism that requires the activation of the sigma factor
CarQ. Bearing in mind that M. xanthus is not very resistant to copper, it is
speculated that the complexity of its copper response might be related to its
complex life cycle.
PMID- 29961778
TI - Diagnosis of immunomarkers in vivo via multiplexed surface enhanced Raman
spectroscopy with gold nanostars.
AB - In this work, we demonstrate the targeted diagnosis of immunomarker programmed
death ligand 1 (PD-L1) and simultaneous detection of epidermal growth factor
receptor (EGFR) in breast cancer tumors in vivo using gold nanostars (AuNS) with
multiplexed surface enhanced Raman spectroscopy (SERS). Real-time longitudinal
tracking with SERS demonstrated maximum accumulation of AuNS occurred 6 h post
intravenous (IV) delivery, enabling detection of both biomarkers simultaneously.
Raman signal correlating to both PD-L1 and EGFR decreased by ~30% in control
tumors where receptors were pre-blocked prior to AuNS delivery, indicating both
the sensitivity and specificity of SERS in distinguishing tumors with different
levels of PD-L1 and EGFR expression. Our in vivo study was combined with the
first demonstration of ex vivo SERS spatial maps of whole tumor lesions that
provided both a qualitative and quantitative assessment of biomarker status with
near cellular-level resolution. High resolution SERS maps also provided an
overview of AuNS distribution in tumors which correlated well with the vascular
density. Mass spectrometry showed AuNS accumulation in tumor and liver, and
clearance via spleen, and electron microscopy revealed AuNS were endocytosed in
tumors, Kupffer cells in the liver, and macrophages in the spleen. This study
demonstrates that SERS-based diagnosis mediated by AuNS provides an accurate
measure of multiple biomarkers both in vivo and ex vivo, which will ultimately
enable a clinically-translatable platform for patient-tailored immunotherapies
and combination treatments.
PMID- 29961780
TI - Dispersity, mesoporous structure and particle size modulation of hollow
mesoporous silica nanoparticles with excellent adsorption performance.
AB - Hollow mesoporous silica nanoparticles (HMSNs) with different dispersities,
mesoporous structures and particle sizes have been systematically synthesized by
simply changing the octadecyltrimethoxysilane (C18TMS, mesopore-forming agent)
percentage of the total silica sources over a wide range. The effects of the
C18TMS percentage on the dispersity, mesoporous structure and particle size of
HMSNs have been discussed in detail based on elaborate structure
characterization. In addition, the volume of the core-etching agent and etching
time have been adjusted carefully to further modulate the mesoporous structure of
HMSNs. Encouragingly, the obtained HMSNs show excellent performance in removing
organic pollutants with short equilibrium adsorption time, high adsorption
capacity and outstanding recyclability. It is believed that these prepared HMSNs
with different dispersities, mesoporous structures and particle sizes possess the
potential to be used in many fields.
PMID- 29961781
TI - Nanoscale liquid crystal lubrication controlled by surface structure and film
composition.
AB - Liquid crystals have emerged as potential candidates for next-generation
lubricants due to their tendency to exhibit long-range ordering. Here, we
construct a full atomistic model of 4-cyano-4-hexylbiphenyl (6CB) nematic liquid
crystal lubricants mixed with hexane and confined by mica surfaces. We explore
the effect of the surface structure of mica, as well as lubricant composition and
thickness, on the nanoscale friction in the system. Our results demonstrate the
key role of the structure of the mica surfaces, specifically the positions of
potassium (K+) ions, in determining the nature of sliding friction with monolayer
lubricants, including the presence or absence of stick-slip dynamics. With the
commensurate setup of confining surfaces, when the grooves created between the
periodic K+ ions are parallel to the sliding direction we observe a lower
friction force as compared to the perpendicular situation. Random positions of
ions exhibit even smaller friction forces with respect to the previous two cases.
For thicker lubrication layers the surface structure becomes less important and
we observe a good agreement with the experimental data on bulk viscosity of 6CB
and the additive hexane. In case of thicker lubrication layers, friction may
still be controlled by tuning the relative concentrations of 6CB and hexane in
the mixture.
PMID- 29961783
TI - Rational design of nano-architecture composite hydrogel electrode towards high
performance Zn-ion hybrid cell.
AB - In this paper, we developed a novel Zn-ion hybrid cell based on a graphene
conducting polymer composite hydrogel (capacitor-type) cathode and a zinc metal
(battery-type) anode. The pseudocapacitive-type cathode materials can effectively
boost the capacity of Zn-ion hybrid cell compared to that of electrical double
layer cathode materials. In particular, the composite hydrogel with rational
designed three-dimensional (3D) nano-architecture combining 3D porous
nanostructure with hydrogel, can significantly enlarge the active interfaces
between the electrode and electrolyte. According to our experiments, the 3D
graphene@PANI composite hydrogel electrode exhibits a large capacity of 154 mA h
g-1, a superior rate capability and excellent capacity retention of 80.5% after
6000 charge-discharge cycles in a Zn-ion hybrid cell. The outstanding
electrochemical properties demonstrate that the 3D nanostructure composite
hydrogel materials can effectively promote the material utilization, transport of
charges, and reduce the degradation of conducting polymers, leading to a highly
efficient, fast and stable electrochemical process. Based on our results, Zn-ion
hybrid cells based on a composite hydrogel electrode could be an extremely
promising candidate for next generation electrochemical energy storage devices.
PMID- 29961784
TI - Exopolysaccharides from olive brines could reduce the adhesion of ETEC K88 to
intestinal epithelial cells.
AB - This study aims to explore the biological functions of the isolated
exopolysaccharides (EPSs) produced during the industrial fermentation of olives
against enterotoxigenic E. coli (ETEC) K88. Exopolysaccharides were isolated from
five industrial fermenters. Analysis of their monosaccharide composition by GLC
revealed that the main components were glucose (27%-50%) and galactose (23%-33%)
followed by rhamnose (4-23%) and arabinose (6-17%). The 1H NMR spectrum showed a
very similar profile between samples, and a more in-depth analysis revealed the
presence of an alpha-pyranose in the form of alpha-d-Glcp-(1->) and two different
alpha-furanoses, with chemicals shift values, suggesting the presence of alpha-d
Glcf and alpha-d-Galf. Miniaturized in vitro tests demonstrated the ability of
EPS samples to attach specifically to ETEC K88 (P < 0.05) with variable
intensities. The competition test did not show the ability to block the ETEC K88
adhesion to IPEC-J2 cells; however, in the displacement test, all EPS samples
were shown to effectively remove the pathogens attached to the cells (P < 0.01).
These results suggest that the EPSs produced during the fermentation of table
green olives could interfere with the attachment of opportunistic pathogens onto
the intestinal epithelial cells. This would open the possibility of novel
functional properties for this traditional Mediterranean fermented food and for
the isolated EPSs as candidates for nutraceutics to be used in human and/or
animal diets in the prevention and treatment of ETEC diarrhoea.
PMID- 29961782
TI - Deciphering hot- and multi-exciton dynamics in core-shell QDs by 2D electronic
spectroscopies.
AB - Although the harnessing of multiple and hot excitons is a prerequisite for many
of the groundbreaking applications of semiconductor quantum dots (QDs), the
characterization of their dynamics through conventional spectroscopic techniques
is cumbersome. Here, we show how a careful analysis of 2DES maps acquired in
different configurations (BOXCARS and pump-probe geometry) allows the tracking
and visualization of intraband Auger relaxation mechanisms, driving the hot
carrier cooling, and interband bi- and tri-exciton recombination dynamics. The
results obtained on archetypal core-shell CdSe/ZnS QDs suggest that, given the
global analysis of the resulting datasets, 2D electronic spectroscopy techniques
can successfully and efficiently dispel the intertwined dynamics of fast and
ultrafast recombination processes in nanomaterials. Hence, we propose this
analysis scheme to be used in future research on novel quantum confined systems.
PMID- 29961785
TI - Visible light-induced Ag nanoparticle deposited urchin-like structures for
enhanced SERS application.
AB - A simple and new fabrication method of Ag nanoparticle deposited "urchin-like"
structures has been reported by the visible light-induced approach. The as
synthesized structures show the deposition of ~5 nm sized Ag nanoparticles with
nanogaps, which can generate highly enhanced electromagnetic fields for higher
activity of surface-enhanced Raman scattering. Thus, these structures are
important for highly sensitive Raman scattering activity.
PMID- 29961786
TI - Selenoprotein-U (SelU) knockdown triggers autophagy through PI3K-Akt-mTOR pathway
inhibition in rooster Sertoli cells.
AB - Selenium (Se) is a major component of male reproduction which exerts its effects
via selenoproteins. Selenoprotein U (SelU), a newly identified protein, is
expressed highly in eukaryotes and possesses a conserved motif similar to that
existing in other thiol-dependent redox regulating selenoproteins; however its
function is unknown. To investigate the role of SelU in testis autophagic and/or
apoptosis cell death mechanisms, we established a Sertoli cell (SC) model
isolated from 45 day old layer roosters. Small interfering RNA (siRNA) technology
was used to develop SelU-knockdown (SelU-KD) and normal (N) SC models. Consequent
to transfection, electron microscopy, qPCR, and western blot were performed. The
results show that the mRNA and proteins of autophagy and anti-apoptosis genes
increased while that of anti-autophagic mammalian target of rapamycin (mTOR) and
pro-apoptosis genes decreased significantly in SelU-KD in contrast to N cells.
Simultaneously, in contrast to N cells the expression of phosphoinositide-3
kinase (PI3K) and protein kinase B (PKB/Akt) both at the mRNA and protein levels
decreased significantly in SelU-KD cells. In-addition, SelU depletion altered the
expression of regulatory factors and increased the mRNA of TSC (tuberous
sclerosis complex) genes as compared to N cells. Extensive autophagosome
formation and lysosome degradation with an intact cytoskeleton were observed in
SelU-KD cells. Our data indicate that SelU deprivation elicits autophagy and
reduces the expression of important growth factors in SCs by disrupting the PI3K
Akt-mTOR signaling pathway. However SelU attenuation did not induce apoptosis in
rooster SCs. Taken together, we conclude that SelU is essential for the survival
and normal functioning of SCs.
PMID- 29961788
TI - Synthesis of acyloxyl pyrazolines by copper-mediated aminoacyloxylation of
unsaturated ketohydrazones.
AB - An efficient and step-economical copper-mediated intra-/intermolecular
aminoacyloxylation of beta,gamma-unsaturated hydrazones has been developed.
Copper carboxylates serve as both reaction promoters and carboxylate sources in
these easily conducted reactions. This method provides straightforward access to
diversely useful acyloxyl pyrazolines, which are hard to access traditionally, in
good to excellent yields.
PMID- 29961787
TI - Administration of Lactobacillus paracasei ameliorates type 2 diabetes in mice.
AB - Probiotics have been proposed as an option for the prevention of type 2 diabetes
mellitus (T2DM). The objective of this study was to evaluate the hypoglycemic
effects of Lactobacillus paracasei on diabetic mice and explore the possible
underlying molecular mechanism. The alpha-glucosidase inhibitory activities of
eight L. paracasei strains were assessed in vitro. L. paracasei TD062 with high
alpha-glucosidase inhibitory activity (31.9%) showed an excellent antidiabetic
ability and it could survive in simulated gastrointestinal juices. To investigate
the beneficial effects of L. paracasei TD062, diabetic mice were treated with the
strain at 109, 108 and 107 CFU ml-1. The results indicated that the
administration of L. paracasei TD062 could regulate the levels of fasting blood
glucose (FBG), postprandial blood glucose (PBG), glucose tolerance, hepatic
glycogen and lipid metabolism. In addition, the antioxidant capacity was also
improved by oral administration of L. paracasei TD062. And the hypoglycemic
effects exhibited dose dependence to some extent. Furthermore, it was revealed
that L. paracasei TD062 had a positive effect on the expression levels of genes
related to glucose metabolism and the PI3K/Akt pathway. These results
demonstrated that L. paracasei TD062 played an important role in preventing the
development of T2DM and might be applied as a new type of hypoglycemic agent in
functional foods.
PMID- 29961789
TI - Thermodynamic features and enthalpy relaxation in a metal-organic framework
glass.
AB - In this work, we explore the thermodynamic evolution in a melt-quenched metal
organic framework glass, formed from ZIF-62 upon heating to the melting point
(Tm), and subsequent enthalpy relaxation. The temperature dependence of the
difference in Gibbs free energy between the liquid and crystal states of ZIF-62
in the temperature range from the glass transition temperature (Tg) to Tm is
found to be weaker than those of other types of glasses, e.g., metallic glasses.
Additionally, we find that the stretched exponent of the enthalpy relaxation
function in the glass varies significantly (beta = 0.44-0.76) upon changing the
extent of sub-Tg annealing, compared to metallic and oxide glasses with similar
Tgs, suggesting a high degree of structural heterogeneity. Pair distribution
function results suggest no significant structural changes during the sub-Tg
relaxation in ZIF-62 glass.
PMID- 29961790
TI - Direct label-free imaging of brain tissue using synchrotron light: a review of
new spectroscopic tools for the modern neuroscientist.
AB - The incidence of brain disease and brain disorders is increasing on a global
scale. Unfortunately, development of new therapeutic strategies has not increased
at the same rate, and brain diseases and brain disorders now inflict substantial
health and economic impacts. A greater understanding of the fundamental
neurochemistry that underlies healthy brain function, and the chemical pathways
that manifest in brain damage or malfunction, are required to enable and
accelerate therapeutic development. A previous limitation to the study of brain
function and malfunction has been the limited number of techniques that provide
both a wealth of biochemical information, and spatially resolved information
(i.e., there was a previous lack of techniques that provided direct biochemical
or elemental imaging at the cellular level). In recent times, a suite of direct
spectroscopic imaging techniques, such as Fourier transform infrared spectroscopy
(FTIR), X-ray fluorescence microscopy (XFM), and X-ray absorption spectroscopy
(XAS) have been adapted, optimized and integrated into the field of neuroscience,
to fill the above mentioned capability-gap. Advancements at synchrotron light
sources, such as improved light intensity/flux, increased detector sensitivities
and new capabilities of imaging/optics, has pushed the above suite of techniques
beyond "proof-of-concept" studies, to routine application to study complex
research problems in the field of neuroscience (and other scientific
disciplines). This review examines several of the major advancements that have
occurred over the last several years, with respect to FTIR, XFM and XAS
capabilities at synchrotron facilities, and how the increases in technical
capabilities have being integrated and used in the field of neuroscience.
PMID- 29961791
TI - Etoposide loaded layered double hydroxide nanoparticles reversing chemoresistance
and eradicating human glioma stem cells in vitro and in vivo.
AB - Glioblastoma (GBM) is the most malignant and lethal glioma in human brain tumors
and contains self-renewing, tumorigenic glioma stem cells (GSCs) that contribute
to tumor initiation, therapeutic resistance and further recurrence. In this
study, we combined in vitro cellular efficacy with in vivo antitumor performance
to evaluate the outcome of an etoposide (VP16) loaded layered double hydroxide
(LDH) nanocomposite (L-V) on human GSCs. The effects on GSC proliferation and
apoptosis showed that loading with LDH could significantly sensitize GSCs to VP16
and enhance the GSC elimination. Further qPCR and western blot assays
demonstrated that L-V could effectively attenuate GSC related pluripotency gene
expression and reduce the cancer stemness. An in vivo GSC xenograft mice model
showed that L-V can overcome drug resistance, eradicate GSCs, sharply decrease
the stemness and reverse the epithelial-mesenchymal transition (EMT). RNA-seq
analysis elucidated that L-V plays a vital role by down-regulating the
PI3K/AKt/mTOR expression and activating the Wnt/GSK3beta/beta-catenin signaling
pathway, hence leading to GSC stemness loss and greatly enhancing the GSC
targeting effect. Taken together, this study demonstrated the outstanding
performance of L-V reversing the drug resistance of GSCs, thus providing a novel
strategy for clinical translation application of nanomedicine in malignant glioma
chemotherapy.
PMID- 29961792
TI - Proline hydroxylation at different sites in hypoxia-inducible factor 1alpha
modulates its interactions with the von Hippel-Lindau tumor suppressor protein.
AB - Hypoxia-inducible factor 1 (HIF-1) plays an essential role in the regulation of
hypoxia in humans. This regulation is mediated by the interaction of the von
Hippel-Lindau tumor suppressor protein (pVHL) with the hydroxylated HIF-1alpha at
proline564 (Pro564). Experimental studies reported that Pro567 could also be
hydroxylated. However, the conformational dynamics of the complex of pVHL with
hydroxylated HIF-1alpha at Pro564 is not well understood, and whether
hydroxylated Pro567 plays the similar essential role as Pro564 in regulating HIF
1alpha-pVHL interaction remains elusive. Herein, we performed all-atom molecular
dynamics (MD) simulations on the pVHL/HIF-1alpha complexes with single
hydroxylation at Pro564 and Pro567, double hydroxylation at both Pro564 and
Pro567, and without hydroxylation. Our multiple MD simulations and binding energy
calculations show that hydroxylation at Pro567 is less favorable for the binding
of HIF-1alpha to pVHL, whereas hydroxylation at Pro564 results in an increase of
structural rigidity of the pVHL/HIF-1alpha complex and an enhancement of the
interactions between HIF-1alpha and pVHL. The different roles revealed here for
Pro564 and Pro567 in regulating HIF-1alpha-pVHL interactions, together with the
previous finding that HIF-prolyl hydroxylase PHD-3 participates in a negative
feedback loop controlling the HIF-1 level, suggest that hydroxylated HIF-1alpha
at Pro567 may perturb or may not participate in this negative feedback loop.
Intriguingly, our simulation data and community network analysis demonstrate that
the binding of hydroxylated HIF-1alpha at Pro564 to the beta-domain of pVHL
allosterically induces the conformational change of the alpha-domain via an
optimal communication pathway from Pro564 of HIF-1alpha to S168 of the pVHL alpha
domain. This study reveals the different roles of Pro564 and Pro567 hydroxylation
in HIF-1alpha in HIF-1alpha-pVHL interactions, which will be beneficial for
developing effective strategies to treat hypoxia-related diseases and
understanding the molecular basis of hypoxic training/exercise.
PMID- 29961793
TI - Ultra-sensitive fluorescent probes for hypochlorite acid detection and
exogenous/endogenous imaging of living cells.
AB - Two fluorescent probes (Naph-1 and Naph-2), which can be prepared via a facile
process, have been developed to detect hypochlorite acid (HOCl). The N,N-dimethyl
thiocarbamate group quenches the fluorescence of the probes through
intramolecular charge transfer (ICT). Upon reaction with HOCl in aqueous buffer,
Naph-1 shows ultra-high sensitivity towards HOCl through a 4600-fold increase in
fluorescence intensity, as well as a detection limit of 2.37 nM. The probes have
been applied to confocal fluorescence imaging of exogenous and endogenous HOCl in
living cells.
PMID- 29961794
TI - Synergetic effect of H and He impurities in Ti3AlC2: first principles
calculations.
AB - First principles calculations have been performed to investigate the synergetic
effect of H and He impurities with vacancies in Ti3AlC2. The configurations and
energetics of Hn-He-VAl complexes (n <= 4) and He-He/He-H/H-H interactions have
been studied. It is found that the impurity H atom prefers to occupy the
tetrahedral interstitial site (Itetr-3), but the He atom prefers to occupy the
octahedral interstitial site (Ioct-4) in perfect Ti3AlC2. Within a pre-existing
Al vacancy, the most favorable site for a He atom is close to tetr-site,
meanwhile the H atom preferentially deviates from the vacancy center with the
separation 1.3 A along the 001 direction. He-H and He-He show a weakly attractive
interaction, but weak repulsion occurs in the H-H interaction, which is different
from the case of Ti3SiC2. The He-VAl complex plays an important role in the
trapping of H atoms. The He-VAl cluster can trap up to three H atoms in the
absence of H2 molecules, which leads to the formation of a H-He hybridized
bubble. Thus, the He atom can subsequently suppress further aggregation of H
atoms and block hydrogen embrittlement and volume swelling.
PMID- 29961795
TI - Assessment of the performance of triphenylphosphine for the voltammetric
determination of elemental sulphur in cosmetic products.
AB - In this paper, an alternative voltammetric method for the determination of
elemental sulphur in cosmetic products is presented. It is based on the decrease
of triphenylphosphine oxidation current in the presence of elemental sulphur by
using a glassy carbon electrode. A solution of 2% (m/v) acetic acid and 0.6 mol L
1 sodium acetate in methanol was used as a supporting electrolyte. The
experimental conditions for indirect determination of elemental sulphur were
established. Using square-wave voltammetry, the analytical curve was linear in
the elemental sulphur concentration range of 9.94-271 MUmol L-1, with a detection
limit of 2.59 MUmol L-1. The method was successfully applied to determine
elemental sulphur in soap bars and anti-acne cream, without any preliminary
sample treatment, therefore, it is shortened and simplified. The results obtained
with the indirect voltammetric method were not statistically different in
comparison with a titrimetric one, at a 95% confidence level. Additionally,
excellent recovery percentages were obtained, proving no matrix interferences.
PMID- 29961796
TI - A new stable luminescent Cd(ii) metal-organic framework with fluorescent sensing
and selective dye adsorption properties.
AB - A new luminescent metal-organic framework, {[Cd3(HL)2(H2O)3].3H2O.2CH3CN}n (1)
(H4L = 1-(3,5-dicarboxylatobenzyl)-3,5-pyrazole dicarboxylic acid), has been
synthesized by solvothermal reaction and characterized by infrared spectroscopy,
powder X-ray diffraction, thermogravimetry measurements and so on. 1 shows a new
trinodal (4,4,6)-connected topology. Importantly, 1 displays intense luminescence
in the solid state and high luminescent sensitivity and selectivity for Fe3+,
CrO42- and Cr2O72- ions in aqueous solution, making it a potential probe for
detecting these substances. The quenching mechanisms are also further discussed
in detail. In addition, further research on the adsorption of dyes shows that 1
can selectively adsorb Congo red dye from other dye molecules.
PMID- 29961797
TI - Ultrafast proton-assisted tunneling through ZrO2 in dye-sensitized SnO2-core/ZrO2
shell films.
AB - Core-shell architectures are used to modulate injection and recombination in dye
sensitized photoelectrochemical cells. Here, we demonstrate that exposing SnO2
core/ZrO2-shell films to acid permits photoinduced electron transfer through ZrO2
shells at least 4 nm thick. A novel mechanism of charge transfer is proposed
where protonic defects permit ultrafast trap-assisted tunneling of electrons.
PMID- 29961798
TI - Miniature diamond-anvil cells for FTIR-microspectroscopy of small quantities of
biosamples.
AB - Fourier transform infrared (FTIR) spectroscopy techniques and data analyses have
become widely available, are easy to use, and are convenient for studies of
various biosamples, especially in biomedical science. Yet, cultivation of cells
and purification of cell components are costly, often methodically challenging,
and time and labor consuming. Therefore, reduction of the sample amount is of
high value. Here we propose a novel method for the analysis of small quantities
of biosamples by FTIR-microscopy of dry films using a diamond-anvil cell (DAC).
This approach allows us to decrease the sample volume at least a hundred times
compared to that for a high-throughput screening device (HTS-XT, Bruker,
Germany), while still obtaining homogeneous films, acquiring qualitative spectra,
and using a conventional 15* objective instead of an ATR-objective. Both FTIR
methods were applied for analyses of human colorectal cancer cell lines SW480 and
SW620 cultured under hypoxic conditions to estimate the strengths and weaknesses
of each approach. FTIR absorption spectra acquired by both methods were compared
and no significant spectral differences were detected. It was shown that FTIR
microscopy of films on the DAC can be used for evaluation, screening,
discrimination and identification of biochemical markers in biosamples like
cells. We conclude that the DAC can be transferred to other biosamples like
tissues, biofluids, their components and extracellular matrix, and is especially
valuable when the available quantities of biosamples are limited.
PMID- 29961799
TI - CeO2-x nanorods with intrinsic urease-like activity.
AB - The large-scale production and ecotoxicity of urea make its removal from
wastewater a health and environmental challenge. Whereas the industrial removal
of urea relies on hydrolysis at elevated temperatures and high pressure, nature
solves the urea disposal problem with the enzyme urease under ambient conditions.
We show that CeO2-x nanorods (NRs) act as the first and efficient green urease
mimic that catalyzes the hydrolysis of urea under ambient conditions with an
activity (kcat = 9.58 * 101 s-1) about one order of magnitude lower than that of
the native jack bean urease. The surface properties of CeO2-x NRs were probed by
varying the Ce4+/Ce3+ ratio through La doping. Although La substitution increased
the number of surface defects, the reduced number of Ce4+ sites with higher Lewis
acidity led to a slight decrease of their catalytic activity. CeO2-x NRs are
stable against pH changes and even to the presence of transition metal ions like
Cu2+, one of the strongest urease inhibitors. The low costs and environmental
compatibility make CeO2-x NRs a green urease substitute that may be applied in
polymer membranes for water processing or filters for the waste water
reclamation. The biomimicry approach allows the application of CeO2-x NRs as
functional enzyme mimics where the use of native or recombinant enzyme is
hampered because of its costs or operational stability.
PMID- 29961800
TI - Two {ZnDyIII} complexes supported by monophenoxido/dicarboxylate bridges with
multiple relaxation processes: carboxylato ancillary ligand-controlled magnetic
anisotropy in square antiprismatic DyIII species.
AB - Two linear-shaped heterometallic trinuclear {ZnII2DyIII} clusters were prepared
with a compartmental Schiff-base ligand and carboxylate as the co-ligand. The
central DyIII ion is sandwiched by two [ZnHhms(RCOO)2] (H2hms = (2-hydroxy-3
methoxybenzylidene)-semicarbazide) units to form a distorted square antiprismatic
(SAP) geometry with D4d symmetry. The DyIII and ZnII ions are triply bridged by
one unique monophenoxido/dicarboxylate group, where one of the carboxylates shows
a severe angular distortion. The magnetic analysis revealed a field-dependent
change with two relaxation processes in 1 and 2, which originated from the
molecular magnetic center and dipolar-dipolar coupling. The dipole-induced slow
relaxation disappeared upon magnetic-site dilution, while another faster
relaxation appeared in the high frequency region associated with the different
distortions of the antiprismatic sites for 1 and disordered structures for 2. Ab
initio calculations revealed that two {ZnII2DyIII}-carboxylate complexes are
axial in nature, but the remarkable quantum tunnelling of the magnetization
exists in the ground state, which lowers the anisotropic barrier and prohibits
zero-field single-molecule magnet behavior. The crystal field of the carboxylato
ancillary ligands produces a competitive effect with the phenoxido bridging
ligands on the magnetic anisotropy of the lanthanide ions, which greatly affects
the electrostatic distribution of this type of {ZnII2DyIII} single-ion magnets
(SIMs). The results offer a model for further investigating structural factors in
the relaxation mechanism of SIM systems.
PMID- 29961801
TI - Kinetic analysis methods applied to single motor protein trajectories.
AB - Molecular motors convert chemical or electrical energy into mechanical
displacement, either linear or rotary. Under ideal circumstances, single-molecule
measurements can spatially and temporally resolve individual steps of the motor,
revealing important properties of the underlying mechanochemical process.
Unfortunately, steps are often hard to resolve, as they are masked by thermal
noise. In such cases, details of the mechanochemistry can nonetheless be
recovered by analyzing the fluctuations in the recorded traces. Here, we expand
upon existing statistical analysis methods, providing two new avenues to extract
the motor step size, the effective number of rate-limiting chemical states per
translocation step, and the compliance of the link between the motor and the
probe particle. We first demonstrate the power and limitations of these methods
using simulated molecular motor trajectories, and we then apply these methods to
experimental data of kinesin, the bacterial flagellar motor, and F1-ATPase.
PMID- 29961802
TI - A synthetic channel that efficiently inserts into mammalian cell membranes and
destroys cancer cells.
AB - Despite the fact that a large number of synthetic channels have been developed in
the last three decades, few of them can function in mammalian cell membranes
because of their weak membrane insertion abilities. This study describes a
tubular molecule with terminal positively charged amino groups that displays a
strong ability to insert into lipid bilayers composed of phosphatidylcholine and
consequently forming unimolecular transmembrane channels. It has been
demonstrated that the insertion of the channel into the phosphatidylcholine
bilayers was driven by the electrostatic interaction between the positively
charged amino groups of the channel molecules and the negatively charged
phosphate groups of the lipid molecules. The high affinity of the channels for
lipid bilayers led to efficient mammalian cell membrane insertion. The channels
showed high effective activity against HepG2 cancer cells at concentrations above
5.1 MUM.
PMID- 29961803
TI - Human histone demethylase KDM6B can catalyse sequential oxidations.
AB - Jumonji domain-containing demethylases (JmjC-KDMs) catalyse demethylation of
Nepsilon-methylated lysines on histones and play important roles in gene
regulation. We report selectivity studies on KDM6B (JMJD3), a disease-relevant
JmjC-KDM, using synthetic lysine analogues. The results unexpectedly reveal that
KDM6B accepts multiple Nepsilon-alkylated lysine analogues, forming alcohol,
aldehyde and carboxylic acid products.
PMID- 29961804
TI - Whole genome comparison of two Starmerella bacillaris strains with other wine
yeasts uncovers genes involved in modulating important winemaking traits.
AB - Starmerella bacillaris is an osmotolerant yeast with interesting winemaking
traits such as low-ethanol and high-glycerol production, previously considered as
wine spoilage and recently proposed to improve the sensory quality of wine. This
is the first work performing a whole-genome analysis of the variants identified
by comparing two S. bacillaris strains (PAS13 and FRI751). Additionally, an
extensive search for orthologous genes against Saccharomyces and non
Saccharomyces yeasts produced a detailed reconstruction of the pan-genome for
yeast species used in winemaking. Starmerella bacillaris PAS13 was able to
produce 36% more glycerol than S. bacillaris FRI751 without increasing ethanol
level over 5% (v/v). Orthologous genes revealed new insights in the response to
osmotic stress determined by the mitogen-activated protein kinase (MAPK) from S.
bacillaris strains. The comparison between the two S. bacillaris genomes revealed
33 771 high-quality variants that were ranked considering their predicted impact
on gene functions. Furthermore, analysis of structural variations in the genome
revealed five translocations. The absence of some transcriptional factors
involved in the regulation of GPD (glycerol-3-phosphate dehydrogenase), like the
protein kinases YpK1p and YpK2p, and the identification of a tandem duplication
increasing the GPP1 (glycerol-3-phosphate phosphatase) gene copy number suggest a
remarkably different regulation of the glycerol pathway for S. bacillaris in
comparison to S. cerevisiae.
PMID- 29961807
TI - Investigating causality in associations between education and smoking: a two
sample Mendelian randomization study.
AB - Background: Lower educational attainment is associated with increased rates of
smoking, but ascertaining causality is challenging. We used two-sample Mendelian
randomization (MR) analyses of summary statistics to examine whether educational
attainment is causally related to smoking. Methods and Findings: We used summary
statistics from genome-wide association studies (GWAS) of educational attainment
and a range of smoking phenotypes (smoking initiation, cigarettes per day,
cotinine levels and smoking cessation). Of 74 single nucleotide polymorphisms
(SNPs) that predict educational attainment, 57 (or their highly correlated
proxies) were present in the smoking initiation, cigarettes per day and smoking
cessation GWAS, and 72 in the cotinine GWAS. Various complementary MR techniques
(inverse variance weighted regression, MR Egger, weighted median regression) were
used to test the robustness of our results. We found broadly consistent evidence
across these techniques that higher educational attainment leads to reduced
likelihood of smoking initiation, reduced heaviness of smoking among smokers (as
measured via self-report [e.g. inverse variance weighted beta -2.25, 95%
confidence interval (CI) -3.81, -0.70, P = 0.005] and cotinine levels [e.g.
inverse variance weighted beta -0.34, 95% CI -0.67, -0.01, P = 0.057]), and
greater likelihood of smoking cessation among smokers (inverse variance weighted
beta 0.65, 95% CI 0.35, 0.95, P = 5.54 * 10-5). Less consistent across the
different techniques were associations between educational attainment and smoking
initiation. Conclusions: Our findings indicate a causal association between low
educational attainment and increased risk of smoking, and may explain the
observational associations between educational attainment and adverse health
outcomes such as risk of coronary heart disease.
PMID- 29961808
TI - Training to implement a community program has positive effects on health
promoters: JC FAMILY Project.
AB - To ease the shortage of professionals, lay volunteers were trained to become
health promoters and role models for a large community program to enhance
physical activity, well-being, and neighborhood cohesion in socioeconomically
disadvantaged groups in Hong Kong. This study aimed to examine the effects on
health promoters (trainees) and the feasibility and acceptability of capability
building train-the-trainer workshops (TTTs) using Zero-time Exercise (ZTEx) to
implement a community program for about 1,000 participants. A four-session
(totally 8 hours) TTT introduced an evidence-based ZTEx intervention to enhance
physical activity and well-being, and build capacity for community program
implementation. Twenty-eight trainees actively participated in the TTT. Twenty
five and 21 trainees completed the 1- and 3-month questionnaires, respectively.
Eleven trainees attended the 1-year focus group interview. Repeated measures
analysis of variance and Friedman test were used to compare the parametric and
nonparametric data, respectively. Qualitative data were analyzed using thematic
content analysis. The trainees reduced their sedentary behavior and improved
their interpersonal communication skills, knowledge, and attitude toward ZTEx,
grip strength, balance, and perceived well-being. The community participants
reported improvements in neighborhood cohesion and grip strength. The 1-year
qualitative results supported the 3-month quantitative findings. This brief and
innovative TTT affirmed the feasibility of using ZTEx and the role modeling
approach for lay health promoters to reduce sedentary behavior and enhance
physical activity, fitness, and well-being. They then contributed to the
successful implementation of community programs that benefited many. This study
provides a new model for building capacity for health promotion in the community.
PMID- 29961809
TI - Plant Cuttings.
PMID- 29961805
TI - Structure of HIV TAR in complex with a Lab-Evolved RRM provides insight into
duplex RNA recognition and synthesis of a constrained peptide that impairs
transcription.
AB - Natural and lab-evolved proteins often recognize their RNA partners with
exquisite affinity. Structural analysis of such complexes can offer valuable
insight into sequence-selective recognition that can be exploited to alter
biological function. Here, we describe the structure of a lab-evolved RNA
recognition motif (RRM) bound to the HIV-1 trans-activation response (TAR) RNA
element at 1.80 A-resolution. The complex reveals a trio of arginines in an
evolved beta2-beta3 loop penetrating deeply into the major groove to read
conserved guanines while simultaneously forming cation-pi and salt-bridge
contacts. The observation that the evolved RRM engages TAR within a double
stranded stem is atypical compared to most RRMs. Mutagenesis, thermodynamic
analysis and molecular dynamics validate the atypical binding mode and quantify
molecular contributions that support the exceptionally tight binding of the TAR
protein complex (KD,App of 2.5 +/- 0.1 nM). These findings led to the hypothesis
that the beta2-beta3 loop can function as a standalone TAR-recognition module.
Indeed, short constrained peptides comprising the beta2-beta3 loop still bind TAR
(KD,App of 1.8 +/- 0.5 MUM) and significantly weaken TAR-dependent transcription.
Our results provide a detailed understanding of TAR molecular recognition and
reveal that a lab-evolved protein can be reduced to a minimal RNA-binding
peptide.
PMID- 29961810
TI - Raptor directs Sertoli cell cytoskeletal organization and polarity in the mouse
testis.
AB - Sertoli cells (SCs) play a central role in testis development, and their normal
number and functions are required for spermatogenesis. Although the canonical
tuberous sclerosis complex-mammalian target of rapamycin complex 1(TSC-mTORC1)
pathway is critical for testis development and spermatogenesis, the signaling
mechanisms governing SC functions remain unclear. In this study, we generated two
SC-specific mouse mutants using the Cre-LoxP system. Loss of Raptor (a key
component of mTORC1) caused severe tubular degeneration in the neonatal testis
and adult mice displayed azoospermia, while adult Rheb (an upstream activator for
mTORC1) mutant mice had intact tubules and many sperm in their epididymides.
Disruption of cytoskeletal organization, including actin, microtubules, and SC
intrinsic vimentin, was observed in Raptor but not Rheb mutant mice. We
investigated the reasons for these different effects by whole-transcriptome
sequencing, and found that expression of the tight junction adaptor protein
cingulin was significantly reduced in Raptor mutant mice. The expression profile
of cingulin was synchronous with the differentiation and cytoskeletal dynamics of
SCs in control mice, but was disordered in Raptor mutant mice. Furthermore,
activity of the small GTPase Rac1 was reduced and expression of the guanine
exchange factor for Rac1, Asef, were decreased in Raptor but not Rheb mutant
mice. Collectively, these findings establish novel functions of Raptor,
independent of the canonical Rheb/mTORC1 pathway, in controlling cytoskeletal
homeostasis and cell polarity in SCs, by affecting cingulin expression and Rac1
activity.
PMID- 29961811
TI - Detection of VBNC Vibrio cholerae by RT-Real Time PCR based on differential gene
expression analysis.
AB - The recognition of the viable but non-culturable (VBNC) state of pathogenic
bacteria has brought with it many questions to answer related to the need to
detect and quantify viable bacteria in the environment in an accurate way. To
assess viability of Vibrio cholerae, we developed a RT-Real Time PCR technique
based on differential expression analysis from mRNA deep sequencing data. We
compared two induction conditions to achieve the VBNC state: a bacterial
suspension induced by artificial seawater at 4 degrees C, and the addition of
3',5'-cyclic diguanylic acid. The evaluation of the up-regulated genes in the
induced bacterial samples was compared with a fresh culture in the mid
exponential phase. The data analysis was performed with the NOISeq R-package and
revealed 17 up-regulated genes for induction condition I and 22 up-regulated
genes for induction condition II. Only one region was found to be up-regulated
for both induction conditions. The VCA0656 gene related to the aminoimidazole
riboside kinase protein was detected as the most up-regulated region and used as
a genetic marker to precisely detect the VBNC state in combination with the RT
Real Time PCR technique. This approach describes a novel method to differentiate
the VBNC state of V. cholerae in water samples.
PMID- 29961812
TI - Recovery kinetics of micronucleus formation by fractionated X-ray irradiation in
various types of human cells.
AB - High-dose ionizing radiation is sufficient for breaking DNA strands, leading to
cell death and mutations. By contrast, the effects of fractionated ionizing
radiation on human-derived cells remain unclear. To better understand the
genotoxic effects of fractionated ionizing radiation, as well as the cellular
recovery rate, we investigated the frequency of micronucleus (MN) formation in
various types of human cells. We irradiated cells with fractionated X-ray doses
of 2 Gy at a rate of 0.0635 Gy/min, separated into two to eight smaller doses.
After irradiation, we investigated the frequency of MN formation. In addition, we
investigated the rate of decrease in MN frequency after irradiation with 1 or 2
Gy X-rays at various recovery periods. Fractionated irradiation decreased MN
frequency in a dose-dependent manner. When the total dose of X-rays was the same,
the MN frequencies were lower after fractionated X-ray irradiation than acute
irradiation in every cell type examined. The rate of MN decrease was faster in
KMST-6 cells, which were derived from a human embryo, than in the other cells.
The rate of MN decrease was higher in cells exposed to fractionated X-rays than
in those exposed to acute irradiation. Recovery rates were very similar among
cell lines, except in KMST-6 cells, which recovered more rapidly than other cell
types.
PMID- 29961813
TI - Cisplatin resistance in lung cancer is mediated by MACC1 expression through
PI3K/AKT signaling pathway activation.
AB - One of the major obstacles hindering the treatment of lung cancer (LC) is
chemoresistance; however, its mechanism remains unclear. The overexpression of
the metastasis-associated in colon cancer 1 (MACC1) gene has been demonstrated to
reverse chemoresistance. In the current study, the expression of MACC1 in LC
cells with cisplatin resistance (Cis-Re) was investigated. Cisplatin-resistant
cell sublines (A549/CR and H446/CR) were induced by stepwise escalation of
cisplatin exposure. MTS and flow cytometry assays were performed to measure cell
proliferation and apoptosis, respectively. Western blot analysis and qRT-PCR
assays were performed to determine the changes in signaling pathway-related
protein and mRNA levels, respectively. A nude mouse xenograft model was used for
in vivo experiments. Our results showed that MACC1 expression was increased in
the cisplatin-resistant A549/CR and H446/CR cell lines, and the resistance was
reversed with a decrease of MACC1 expression. MACC1 overexpression triggered an
increase of Cis-Re, which was contrary to the effect of MACC1 down-regulation. In
addition, the effect of MACC1 on Cis-Re was blocked by the inhibition of the
PI3K/AKT pathway, and treatment with both cisplatin and a PI3K/AKT inhibitor
effectively inhibited tumor growth in xenografts with MACC1 overexpression. In
conclusion, our results revealed that MACC1 increased Cis-Re partially via the
PI3K/AKT signaling pathway, suggesting that MACC1 could serve as a potential
target to overcome Cis-Re. Furthermore, combination therapy could alleviate Cis
Re resulted from MACC1 overexpression in patients with LC.
PMID- 29961814
TI - The role of HIV in influenza- and respiratory syncytial virus-associated
hospitalizations in South African children, 2011-2016.
AB - Background: Few data describe influenza- or respiratory syncytial virus (RSV)
associated hospitalized illness in children aged <5 years in sub-Saharan Africa.
Methods: During 2011-2016, we conducted prospective surveillance for severe
respiratory illness (SRI) in children aged <5 years in three South African
hospitals. Nasopharyngeal aspirates were tested for influenza and RSV by real
time reverse transcription polymerase chain reaction. We estimated rates of
influenza- and RSV-associated hospitalized SRI by HIV status and compared
children who tested positive for influenza versus RSV using multivariable
penalized logistic regression. Results: Among 3650 hospitalized children, 203
(5.6%) tested positive for influenza viruses, 874 (23.9%) for RSV, and 19 (0.5%)
for both. The median age of children hospitalized with influenza was 13.9 months
versus 4.4 months for RSV (p<0.01). Annual influenza-associated hospitalization
rates per 100,000 were highest among infants aged 6-11 months (545, 95%
Confidence Interval (CI): 409-703), while RSV-associated hospitalization rates
were highest in infants aged 0-2 months (6593, 95% CI: 5947-7217). HIV exposure
was associated with increased incidence of influenza- and RSV-associated
hospitalization in infants aged 0-5 months, Relative Risk (RR) 2.2 (95% CI: 1.4
3.4) and 1.4 (95% CI: 1.3-1.6), respectively. HIV infection was associated with
increased incidence of influenza- and RSV-associated hospitalization in all age
groups; RR 2.7 (95% CI: 2.0-3.5) and 3.8 (95% CI: 3.1-4.8), respectively. The
case-fatality rate was 0.8% among children hospitalized with influenza or RSV.
Conclusions: Influenza- and RSV-associated hospitalization are common among South
African infants. HIV infection, and HIV exposure in infants, increase risk of
influenza- and RSV-associated hospitalization.
PMID- 29961815
TI - Idiopathic Thrombocytopenic Purpura Responsive to Surgery for Crohn's Disease.
PMID- 29961816
TI - Immuno-monitoring reveals an extended subclinical disease activity in tocilizumab
treated giant cell arteritis.
AB - Objective: Tocilizumab is effective in inducing and maintaining remission of GCA.
Despite clinical and serological control of disease, magnetic resonance
angiography may show persistence of inflammatory signals of unknown significance
in arterial walls. Thus, there is an unmet need for tools to detect subclinical
disease activity. Methods: Immune-inflammatory markers were measured in
prospectively collected sera of the first randomized, double-blind, placebo
controlled trial investigating the use of tocilizumab in GCA. As a comparison,
immune-inflammatory markers were also measured in sera from age- and sex-matched
healthy volunteers. The biomarkers were quantified using luminex technology.
Results: Of all the parameters determined, only MMP-3, pentraxin-3 and sTNFR2
were significantly elevated, while ICAM-1 and CD163 were significantly decreased
during the early stages of the study, at time points of full clinical remission
under treatment with tocilizumab plus glucocorticoids. In contrast, tocilizumab
monotherapy towards the end of the study resulted in an almost complete
normalization of immune-inflammatory molecules, as defined by the healthy
controls. MMP-3 levels showed a weak association with magnetic resonance signal
intensity; none of the biomarkers predicted relapse occurring within 6 months
after study end. Conclusion: The data documented a subclinical disease activity
in GCA that was more pronounced during the early stages of treatment and almost
disappeared towards the study end. They indicated that tocilizumab treatment of
at least 52 weeks is necessary in order to reset a broad range of immune
inflammatory pathways. Trial registration: ClinicalTrials.gov,
http://clinicaltrials.gov, NCT01450137.
PMID- 29961818
TI - Chemical-gene relation extraction using recursive neural network.
AB - In this article, we describe our system for the CHEMPROT task of the BioCreative
VI challenge. Although considerable research on the named entity recognition of
genes and drugs has been conducted, there is limited research on extracting
relationships between them. Extracting relations between chemical compounds and
genes from the literature is an important element in pharmacological and clinical
research. The CHEMPROT task of BioCreative VI aims to promote the development of
text mining systems that can be used to automatically extract relationships
between chemical compounds and genes. We tested three recursive neural network
approaches to improve the performance of relation extraction. In the BioCreative
VI challenge, we developed a tree-Long Short-Term Memory networks (tree-LSTM)
model with several additional features including a position feature and a subtree
containment feature, and we also applied an ensemble method. After the challenge,
we applied additional pre-processing steps to the tree-LSTM model, and we tested
the performance of another recursive neural network model called Stack-augmented
Parser Interpreter Neural Network (SPINN). Our tree-LSTM model achieved an F
score of 58.53% in the BioCreative VI challenge. Our tree-LSTM model with
additional pre-processing and the SPINN model obtained F-scores of 63.7 and
64.1%, respectively.Database URL:
https://github.com/arwhirang/recursive_chemprot.
PMID- 29961817
TI - LncCeRBase: a database of experimentally validated human competing endogenous
long non-coding RNAs.
AB - Long non-coding RNAs (lncRNAs) are endogenous molecules longer than 200
nucleotides, and lack coding potential. LncRNAs that interact with microRNAs
(miRNAs) are known as a competing endogenous RNAs (ceRNAs) and have the ability
to regulate the expression of target genes. The ceRNAs play an important role in
the initiation and progression of various cancers. However, until now, there is
no a database including a collection of experimentally verified, human ceRNAs. We
developed the LncCeRBase database, which encompasses 432 lncRNA-miRNA-mRNA
interactions, including 130 lncRNAs, 214 miRNAs and 245 genes from 300
publications. In addition, we compiled the signaling pathways associated with the
included lncRNA-miRNA-mRNA interactions as a tool to explore their functions.
LncCeRBase is useful for understanding the regulatory mechanisms of
lncRNA.Database URL: http://lnccerbase.it1004.com.
PMID- 29961819
TI - dbLGL: an online leukemia gene and literature database for the retrospective
comparison of adult and childhood leukemia genetics with literature evidence.
AB - Leukemia is a group of cancers with increased numbers of immature or abnormal
leucocytes that originated in the bone marrow and other blood-forming organs. The
development of differentially diagnostic biomarkers for different subtypes
largely depends on understanding the biological pathways and regulatory
mechanisms associated with leukemia-implicated genes. Unfortunately, the leukemia
implicated genes that have been identified thus far are scattered among thousands
of published studies, and no systematic summary of the differences between adult
and childhood leukemia exists with regard to the causative genetic mutations and
genetic mechanisms of the various subtypes. In this study, we performed a
systematic literature review of those susceptibility genes reported in small
scale experiments and built an online gene database containing a total of 1805
leukemia-associated genes, available at http://soft.bioinfo-minzhao.org/lgl/. Our
comparison of genes from the four primary subtypes and between adult and
childhood cases identified a number of potential genes related to patient
survival. These curated genes can satisfy a growing demand for further
integrating genomics screening for leukemia-associated low-frequency mutated
genes.Database URL: http://soft.bioinfo-minzhao.org/lgl/.
PMID- 29961820
TI - IsopiRBank: a research resource for tracking piRNA isoforms.
AB - PIWI-interacting RNAs (piRNAs) are essential for transcriptional and post
transcriptional regulation of transposons and coding genes in germline. With the
development of sequencing technologies, length variations of piRNAs have been
identified in several species. However, the extent to which, piRNA isoforms
exist, and whether these isoforms are functionally distinct from canonical piRNAs
remain uncharacterized. Through data mining from 2154 datasets of small RNA
sequencing data from four species (Homo sapiens, Mus musculus, Danio rerio and
Drosophila melanogaster), we have identified 8 749 139 piRNA isoforms from 175
454 canonical piRNAs, and classified them on the basis of variations on 5' or 3'
end via the alignment of isoforms with canonical sequence. We thus established a
database named IsopiRBank. Each isoforms has detailed annotation as follows:
normalized expression data, classification, spatiotemporal expression data and
genome origin. Users can also select interested isoforms for further analysis,
including target prediction and Enrichment analysis. Taken together, IsopiRBank
is an interactive database that aims to present the first integrated resource of
piRNA isoforms, and broaden the research of piRNA biology. IsopiRBank can be
accessed at http://mcg.ustc.edu.cn/bsc/isopir/index.html without any registration
or log in requirement. Database URL:
http://mcg.ustc.edu.cn/bsc/isopir/index.html.
PMID- 29961822
TI - The Impact of (the Concept of) Treatment-Resistant Depression: An Opinion Review.
AB - Treatment-resistant depression refers to major depressive disorder, treatment of
the disorder, and failure to obtain an "acceptable" outcome. Regarding the
disorder, the heterogeneous concept of major depressive disorder and the multiple
definitions of treatment-resistant depression, hesitating between a categorical
and a more dimensional approach, as well as the divergence between diagnostic
criteria and the items in the assessment scales are a source of confusion.
Classifications do not take into account the dramatic influence of patient
characteristics strongly impacting outcome, although these can be the cause of so
called pseudo-resistance. Outcome is the result of spontaneous evolution,
nonspecific factors (including placebo), and active treatment factors. These
should be differentiated to have a reliable estimation of the impact of different
treatment modalities before we can asses treatment-resistant depression or before
we can ascertain the (non)efficacy of treatments for treatment-resistant
depression.The impact and burden of major depressive disorder and treatment
resistant depression are immense and go far beyond their economic cost. It is
often forgotten that both are not only associated with increased suicidality but
also with nonsuicidal mortality and that both can even result in requests for
assisted dying. The caregiver burden and associated stigma are also too often
overlooked despite that it has been suggested that they do influence (treatment)
outcome.
PMID- 29961821
TI - SDADB: a functional annotation database of protein structural domains.
AB - Annotating functional terms with individual domains is essential for
understanding the functions of full-length proteins. We describe SDADB, a
functional annotation database for structural domains. SDADB provides
associations between gene ontology (GO) terms and SCOP domains calculated with an
integrated framework. GO annotations are assigned probabilities of being correct,
which are estimated with a Bayesian network by taking advantage of structural
neighborhood mappings, SCOP-InterPro domain mapping information, position
specific scoring matrices (PSSMs) and sequence homolog features, with the most
substantial contribution coming from high-coverage structure-based domain-protein
mappings. The domain-protein mappings are computed using large-scale structure
alignment. SDADB contains ontological terms with probabilistic scores for more
than 214 000 distinct SCOP domains. It also provides additional features include
3D structure alignment visualization, GO hierarchical tree view, search, browse
and download options.Database URL: http://sda.denglab.org.
PMID- 29961823
TI - Rapid confirmation of the Zaire Ebola Virus in the outbreak of the Equateur
province in the Democratic Republic of Congo: implications for public health
interventions.
AB - Ten days after the declaration of the Ebola outbreak in the Equateur Province of
the Democratic Republic of Congo, rapid identification of the species Zaire
Ebolavirus (EBOV) using partial gene amplification and nanopore sequencing backed
up the use of the rVSV-ZEBOV vaccine in the ring vaccination strategy recommended
by WHO.
PMID- 29961824
TI - Oligomerization of Prph2 and Rom1 is essential for photoreceptor outer segment
formation.
AB - Mutations in peripherin 2 (PRPH2, also known as Rds), a tetraspanin protein found
in photoreceptor outer segments (OSs), cause retinal degeneration ranging from
rod-dominant retinitis pigmentosa (RP) to cone-dominant macular dystrophy (MD).
Understanding why some Prph2 mutants affect rods while others affect cones
remains a critical unanswered question. Prph2 is essential for OS structure and
function and exhibits a very specific pattern of oligomerization with its homolog
Rom1. Non-covalent Prph2/Rom1 homo- and hetero-tetramers assemble into higher
order covalently linked complexes held together by an intermolecular disulfide
bond at Prph2-C150/Rom1-C153. Here we disrupt this crucial bond using a C150S
Prph2 knockin mouse line to study the role of Prph2 higher-order complex
formation. We find that C150S-Prph2 traffics to the OS, interacts with Rom1 and
forms non-covalent tetramers, but alone cannot support normal OS structure and
function. However, C150S-Prph2 supports the initiation or elaboration of OS disc
structures, and improves rod OS ultrastructure in the presence of wild-type (WT)
Prph2 (i.e. Prph2C150S/+ versus Prph2+/-). Prph2C150S/+ animals exhibit
haploinsufficiency in rods, but a dominant-negative phenotype in cones,
suggesting cones have a different requirement for large Prph2 complexes than
rods. Importantly, cone but not rod function can be improved by the addition of
one Prph2Y141C allele, a mutation responsible for pattern dystrophy owing to the
extra cysteine. Combined these findings show that covalently linked Prph2
complexes are essential for OS formation, but not for Prph2 targeting to the OS,
and that cones are especially sensitive to having a broad distribution of Prph2
complex types (i.e. tetramers and large complexes).
PMID- 29961825
TI - Rectal MALT lymphoma regression and anti-Helicobacter pylori therapy.
PMID- 29961826
TI - Parainfluenza Virus in Hospitalized Adults: A 7-Year Retrospective Study.
AB - Background: Parainfluenza virus (PIV) is a cause of respiratory tract infection
in children and the immunocompromised population, but its clinical
manifestations, impact, and outcomes in hospitalized adults are not well studied.
Methods: This retrospective study included adults (>=18 years old) admitted to
Northwestern Memorial Hospital or Prentice Women's Hospital (both in Chicago,
Illinois) between 1 August 2009 and 31 July 2016 with a positive molecular test
result for PIV. Epidemiologic, clinical, and outcomes data were collected from
the enterprise data warehouse and patient electronic health records after
institutional review board approval. Descriptive statistics were used to
summarize the data. Results: A total of 550 adults with a positive molecular test
for PIV were identified. Differences in seasonality, clinical presentation, and
prevalence between the different PIV serotypes (PIV-1, PIV-2, and PIV-3) were
identified. The most common signs/symptoms were cough (88%), productive sputum
(55%), fever (63%), and dyspnea (49%). Of the patients administered antibiotics,
349 (79.6%) had no confirmed bacterial infection throughout their
hospitalization. The average length of hospitalization was 7.7 days. Presence of
bacterial coinfection (P = .01), fungal coinfection (P < .01), decreased body
mass index (P = .03), and increased respiratory rate (P < .01) were associated
with significant differences in mortality rates. Conclusions: PIV infection is
associated with substantial morbidity in hospitalized adults. Such data will be
useful in understanding the impact on epidemiology and outcomes if a PIV-specific
vaccine becomes available. Furthermore, this highlights the need for novel
preventive and therapeutic approaches to PIV infection.
PMID- 29961827
TI - A workflow for simplified analysis of ATAC-cap-seq data in R.
AB - Background: Assay for Transposase-Accessible Chromatin (ATAC)-cap-seq is a high
throughput sequencing method that combines ATAC-seq with targeted nucleic acid
enrichment of precipitated DNA fragments. There are increased analytical
difficulties arising from working with a set of regions of interest that may be
small in number and biologically dependent. Common statistical pipelines for RNA
sequencing might be assumed to apply but can give misleading results on ATAC-cap
seq data. A tool is needed to allow a nonspecialist user to quickly and easily
summarize data and apply sensible and effective normalization and analysis.
Results: We developed atacR to allow a user to easily analyze their ATAC
enrichment experiment. It provides comprehensive summary functions and diagnostic
plots for studying enriched tag abundance. Application of between-sample
normalization is made straightforward. Functions for normalizing based on user
defined control regions, whole library size, and regions selected from the least
variable regions in a dataset are provided. Three methods for detecting
differential abundance of tags from enriched methods are provided, including
bootstrap t, Bayes factor, and a wrapped version of the standard exact test in
the edgeR package. We compared the precision, recall, and F-score of each
detection method on resampled datasets at varying replicate, significance
threshold, and genes changed and found that the Bayes factor method had the
greatest overall detection power, though edgeR was slightly stronger in
simulations with lower numbers of genes changed. Conclusions: Our package allows
a nonspecialist user to easily and effectively apply methods appropriate to the
analysis of ATAC-cap-seq in a reproducible manner. The package is implemented in
pure R and is fully interoperable with common workflows in Bioconductor.
PMID- 29961828
TI - Orthodox and Unorthodox Uses of Electronic Cigarettes: A Surveillance of YouTube
Video Content.
AB - Introduction: Open electronic cigarette (e-cigarette) systems are customizable by
consumers and often allow for potential "unorthodox" use of the product; that is,
use not as intended by the manufacturer. Little is known about the types and
prevalence of unorthodox uses and how these practices are transmitted via popular
social media. Methods: Monthly searches of YouTube were conducted from June
through November 2016 using the search terms: "e-cigarettes", "vaping", and "e
juice". After collecting static and dynamic data on the 150 videos identified,
two coders independently coded videos for general information, unorthodox use
behaviors, health claims, and production quality and characteristics for orthodox
and unorthodox use. Inter coder reliability was high (Cohen's kappa 0.81, p <
.001). Results: One hundred fifty videos were included in the study with a total
of 115,551,563 views. We identified nine categories of unorthodox uses of e
cigarettes. Unorthodox use was three times as prevalent as orthodox use. Seventy
seven percent of the unorthodox use videos included recreational e-cigarette use,
57% included modification of mechanical parts and components, and 44.6% included
unorthodox substance application (dripping). There were more than twice as many
social media links in videos depicting unorthodox compared to orthodox use, but
the level of engagement was lower for unorthodox use. Conclusions: E-cigarette
unorthodox use on YouTube is more prevalent than orthodox use, suggesting the
need to further investigate the prevalence of unorthodox use among e-cigarette
users and the influence of social media on consumer uptake of unorthodox and
orthodox uses of e-cigarettes. Implications: The U.S. Food and Drug
Administration (FDA) has regulatory authority over e-cigarettes, parts and
components. Many e-cigarettes currently marketed are open systems. Closed systems
may allow less manipulation and may influence the safety of these products. This
study provides valuable information on ways that open system e-cigarettes are
used and it can inform safety tests that can be conducted by the FDA to determine
whether or not these products should remain on the market. Additionally, our
definitions of unorthodox use can be incorporated into the Population Assessment
of Tobacco on Health Study to better understand the prevalence of these
behaviors.
PMID- 29961829
TI - Calliphoridae (Diptera) Associated With Rattus rattus Carcasses in the Tijuca
National Park, Rio de Janeiro, Brazil.
AB - Forensic entomology is a complementary tool for penal procedures, mainly on
estimating postmortem interval. Study of cadaveric fauna in various environments
is primary as source of information to support this science. This study collected
information about the fauna of Calliphoridae associated to carcasses of Rattus
rattus in the Tijuca National Park, RJ. Four collections were conducted, one for
each season of 2015, exposing six carcasses at georeferenced points in each
collection. The carcasses were placed 550 m from the boarder and equidistant by
100 m. Five decomposition stages were identified, and 10,559 individuals of
Calliphoridae belonging to 10 species were collected. The most abundant species
were Hemilucilia semidiaphana (Rondani) (Diptera: Calliphoridae) and Lucilia
eximia (Wiedemann) (Diptera: Calliphoridae). L. eximia was the most abundant
species during the Swelling and Black Putrefaction stages, succeeded in the next
stages by two species of the genera Hemilucilia. H. semidiaphana was the dominant
species in the last two stages, followed by Hemilucilia segmentaria (Fabricius)
(Diptera: Calliphoridae). The genus Mesembrinella (Diptera: Calliphoridae)
occurred mainly during the Black putrefaction stage. Mesembrinella bellardiana
(Aldrich) was more abundant, with higher occurrence during the Black putrefaction
and Dry decay stages. Mesembrinella peregrina (Aldrich) occurred in the two last
stages with low abundance. Huascaromusca aeneiventris (Wiedemann) (Diptera:
Calliphoridae) occurred during all the observed stages, mainly during the Butyric
fermentation stage. Huascaromusca purpurata (Aldrich) (Diptera: Calliphoridae)
occurred only during the Dry decay stage and in low abundance. A succession
pattern in the carcasses colonization was observed, providing relevant
information for the resolution of criminal investigations in this environment.
PMID- 29961830
TI - The structure of seminiferous tubules and the development of [spermatids] in
rats.
PMID- 29961831
TI - Molecular diversity of fungal inhibitor cystine knot peptides evolved by domain
repeat and fusion.
AB - Peptides with the inhibitor cystine knot (ICK) motif are extensively present in
animals and plants where they exert a diversity of biological functions. However,
few studies have been undertaken on this class of peptides in fungi. In this
work, we identify a total of 386 fungal ICK peptides and proteins containing this
motif by computational data mining of fungal genome databases, which exhibit 14
different exon-intron structures. According to their domain architectures, these
proteins are classified into three distinct structural types, including single
domains, tandem repeat domains and fusion domains, in which six families
belonging to single or tandem repeat domains show remarkable sequence similarity
to those from animals and plants, suggesting their orthologous relationship.
Extremely high molecular diversity in fungal ICKs might be attributable to
different genetic mechanisms, such as gene/domain duplication and fusion. This
work not only enlarges the number of ICK peptides in multicellular organisms, but
also uncovers their complex evolutionary history in a specific lineage.
PMID- 29961832
TI - Eat, drink and be merry: Leydig cell autophagy in testosterone production.
PMID- 29961833
TI - Update From the Advisory Committee on Immunization Practices.
AB - The Advisory Committee on Immunization Practices (ACIP), a group of medical and
public health experts, meets 3 times per year to develop recommendations for
vaccine use in the United States. There are 15 voting members, and their terms
are for 4 years. ACIP members and Centers for Disease Control and Prevention
staff discuss the epidemiology of vaccine-preventable diseases and vaccine
research, effectiveness, safety data, and clinical trial results. Representatives
from the American Academy of Pediatrics (including D. W. K.) and the Pediatric
Infectious Diseases Society are present as liaisons to the ACIP. In the February
2018 meeting, important votes on the use of influenza vaccine and hepatitis
vaccines were held, and updates on human papillomavirus, meningococcal, and
anthrax vaccines, among others, were provided.
PMID- 29961834
TI - Assessment of human-to-human transmissibility of avian influenza A(H7N9) virus
across five waves by analyzing clusters of case-patients in mainland China, 2013
2017.
AB - Background: The 2016-17 epidemic of human infections with avian influenza A(H7N9)
virus was alarming due to the surge in reported cases across a wide geographic
area and the emergence of highly pathogenic A(H7N9) viruses. Our study aimed to
assess whether human-to-human transmission risk of A(H7N9) virus has changed
across the five waves since 2013. Methods: Data on human cases and clusters of
A(H7N9) virus infection were collected from WHO, national and provincial reports,
informal online sources and published literature. We compared the epidemiological
characteristics and clinical severity of sporadic and cluster cases, estimated
the relative risk (RR) of infection in blood-relatives and non-blood relatives,
and estimated the bounds on the effective reproductive number (Re) across waves
from 2013 through September 2017. Results: 40 human clusters of A(H7N9) virus
infection were identified, with a median cluster size of 2 (range 2-3). The
overall RR of infection in blood-relatives versus non-blood relatives was 1.65
(95% CI 0.88, 3.09), and was not significantly different across waves (chi2=2.66,
P=0.617). The upper and lower limits of Re for A(H7N9) virus were 0.12 (95% CI
0.10, 0.14) and 0.03 (95% CI 0, 0.14), respectively. Re estimates were not
significantly different across waves (chi2=1.52, P=0.822 for upper limit;
chi2=6.58, P=0.160 for lower limit). Conclusions: The small cluster size and low
Re suggest that human-to-human transmissibility of A(H7N9) virus has not changed
over time and remains limited to date. Continuous assessment of A(H7N9) virus
infections and human case clusters is of crucial importance for public health.
PMID- 29961835
TI - Biomechanical characterization and comparison of different aortic root surgical
techniques.
AB - OBJECTIVES: Understanding the biomechanical impact of aortic valve-sparing
techniques is important in an era in which surgical techniques are developing and
are increasingly being used based on biomechanical understanding that is
essential in the refining of existing techniques. The objective of this study was
to describe how the valve-sparing remodelling (Yacoub) and reimplantation (David
Type-1) techniques affect the biomechanics of the native aortic root in terms of
force distribution and geometrical changes. METHODS: Two force transducers were
implanted into 22 pigs, randomized to 1 of 3 groups (David = 7, native = 7 and
Yacoub = 8) along with 11 sonomicrometry crystals and 2 pressure catheters. Force
and geometry data were combined to obtain the local structural stiffness in
different segments of the aortic root. RESULTS: The radial structural stiffness
was not different between groups (P = 0.064) at the annular level; however, the
David technique seemed to stabilize the aortic annulus more than the Yacoub
technique. In the sinotubular junction, the native group was more compliant (P =
0.036) with the right-left coronary segment than the intervention groups.
Overall, the native aortic root appeared to be more dynamic at both the annular
level and the sinotubular junction than both intervention groups. CONCLUSIONS: In
conclusion, the David procedure may stabilize the aortic annulus more than the
Yacoub procedure, whereas the leaflet opening area was larger in the latter (P =
0.030). No difference (P = 0.309) was found in valve-opening delay between
groups. The 2 interventions show similar characteristics at the sinotubular
junction, whereas the David technique seemed more restrictive at the annular
level than the Yacoub technique.
PMID- 29961836
TI - Model selection and parameter inference in phylogenetics using Nested Sampling.
AB - Bayesian inference methods rely on numerical algorithms for both model selection
and parameter inference. In general, these algorithms require a high
computational effort to yield reliable estimates. One of the major challenges in
phylogenetics is the estimation of the marginal likelihood. This quantity is
commonly used for comparing different evolutionary models, but its calculation,
even for simple models, incurs high computational cost. Another interesting
challenge relates to the estimation of the posterior distribution. Often, long
Markov chains are required to get sufficient samples to carry out parameter
inference, especially for tree distributions. In general, these problems are
addressed separately by using different procedures. Nested sampling (NS) is a
Bayesian computation algorithm which provides the means to estimate marginal
likelihoods together with their uncertainties, and to sample from the posterior
distribution at no extra cost. The methods currently used in phylogenetics for
marginal likelihood estimation lack in practicality due to their dependence on
many tuning parameters and their inability of most implementations to provide a
direct way to calculate the uncertainties associated with the estimates, unlike
NS. In this paper, we introduce NS to phylogenetics. Its performance is analysed
under different scenarios and compared to established methods. We conclude that
NS is a competitive and attractive algorithm for phylogenetic inference. An
implementation is available as a package for BEAST 2 under the LGPL licence,
accessible at https://github.com/BEAST2-Dev/nested-sampling.
PMID- 29961837
TI - Strategic Priorities to Improve Effectiveness of Anti-smoking Interventions for
the Korean Military: An Application of the Analytic Hierarchy Process.
AB - Introduction: As South Korea remains technically at war with the North, higher
smoking prevalence in the military might adversely affect the South Korea's
military power and contribute to lifetime smoking in men with mandatory military
service. This study was to identify priorities among the anti-smoking strategies
to improve the existing smoking cessation programs for the Korean military.
Methods: The analytic hierarchy process model with a goal, decision criteria, and
sub-criteria as well as candidate strategies, was developed following a
literature search and expert group discussion. A survey for pairwise comparison
was conducted to determine the priority of the (sub-)criteria and strategies by
14 experts. The Super-Decisions software was used to determine the priorities and
to analyze their consistency ratios and sensitivities. The study was approved by
the ethics committee of the Korea Ministry of Health and Welfare. Results: Eight
candidate strategies were developed to improve the effectiveness of military anti
smoking interventions as follows: (1) development of outcome enhancement plans
for smoking cessation programs for the military, (2) development of
differentiated smoking cessation programs for specific groups, (3) building of
community network for continuity and accessibility of anti-smoking project, (4)
building of industry-academia-government networks for anti-smoking project, (5)
improvement of the perception of and strengthen the reward for smoking cessation,
(6) development of a training system for army clinicians for the delivery of
smoking cessation services, (7) creation of a certification system for smoking
cessation programs, and (8) development of an evaluation system of project
performance for smoking cessation. Through the analytic hierarchy process survey,
the military specificity and its sub-criterion of practicality were selected as
the top concerns of decision criteria for the anti-smoking strategies among the
decision criteria of outcome improvement, military specificity, publicness, and
economic efficiency. The most important strategy was to improve the perception of
and strengthen the reward for smoking cessation. This strategy was most focused
on the creation of an anti-smoking environment and improvement of the
effectiveness of the projects. The creation of a training system for army
clinicians for the delivery of smoking cessation services ranked second.
Conclusion: In conclusion, motivating smoking cessation and utilizing well
trained army clinicians were found to be the most important anti-smoking
strategies for the Korean military. This study might provide valuable insights
for policy makers to reduce tobacco use in the Korean military.
PMID- 29961839
TI - Reliability and Feasibility Considerations in the Assessment of a Malodor
Adaptation Technique: A Pilot Study.
PMID- 29961838
TI - Zolpidem and Eszopiclone Pre-medication for PSG: Effects on Staging, Titration,
and Adherence.
AB - Introduction: The non-benzodiazepine sedative hypnotic (NBSH) eszopiclone
improves polysomnography (PSG) quality and continuous positive airway pressure
(CPAP) adherence. It is unclear whether zolpidem has the same effect and neither
NBSH has been studied in populations with milder forms of obstructive sleep
apnea. Materials and Methods: We performed a retrospective analysis on patients
undergoing level I PSG at our institution. Patients are pre-medicated with NBSHs
at the discretion of the sleep physician. We compared PSG/CPAP titration quality
and subsequent CPAP adherence for patients receiving NBSHs or no pre-study
medication. We adjusted for obstructive sleep apnea pre-test probability (PTP),
arousal threshold, and other factors showing differences at baseline. Results:
Data on 560 patients were analyzed. Mean age and body mass index were 42.2 +/-
10.1 and 28.8 +/- 4.5, respectively. Median apnea hypopnea index was 12.9 (6.4
25.3), 100 (18.0%) patients had normal studies, 97 (17.3%) were split, and 457
(81.6%) had a respiratory low-arousal threshold. After adjusting for differences
at baseline, neither NBSH was associated with sleep efficiency, wake after sleep
onset, or total sleep time on PSG. After adjustment, patients receiving
eszopiclone had a higher apnea hypopnea index at the final CPAP pressure (beta =
14.2; 95% confidence intervals (CI) 7.2-21.2; p < 0.001) and were more likely to
have an unacceptable titration (odds ratio (OR) = 6.6; 95% CI 2.0-21.0; p =
0.002). When only split-night studies were examined, there were no differences in
any adherence variables across or between categories. Conclusions: In a
population with predominantly mild obstructive sleep apnea, NBSHs did not improve
PSG or CPAP titration quality and did not increase CPAP adherence. There was no
difference in effect between eszopiclone and zolpidem.
PMID- 29961840
TI - The Uropathogenic Escherichia coli Subclone ST131-H30 Is Responsible for Most
Antibiotic Prescription Errors at an Urgent Care Clinic.
AB - Background: The pandemic spread of antibiotic resistance increases the likelihood
of ineffective empirical therapy. The recently emerged fluoroquinolone-resistant
Escherichia coli ST131-H30R subclone (H30) is a leading cause of multidrug
resistant urinary tract infection (UTI) and bloodstream infection worldwide.
Objective: We studied the relative impact of H30 on the likelihood that bacteria
isolated from urine of urgent care patients would be resistant to the empirically
prescribed antibiotic regimen for UTI. Results: Of 750 urinalysis-positive urine
samples from urgent care patients with suspected UTI, 306 (41%) yielded E. coli,
from 35 different clonal groups (clonotypes). H30 predominated (14% prevalence
overall), especially among older patients (age 70+ years: 26%) and those with
diabetes (43%) or urinary catheterization (60%). Resistance to the empirically
selected antibiotic regimen occurred in 16% (40/246) of patients overall, 28%
(20/71) of older patients, 30% (8/27) of patients with diabetes, 60% (3/5) of
catheterized patients, and 71% (22/30) of those with H30. H30's contribution to
such mismatched antibiotic selection was 55% overall, 70% among older patients,
and 100% among patients with diabetes or a urinary catheter. Among patients with
>= 2 of these factors (older age, diabetes, or urinary catheter), 24% of all
urinalysis-positive urine samples yielded H30, with a 92% likelihood of
resistance to the selected empirical therapy. Conclusion: The multidrug-resistant
H30 subclone of E. coli ST131 is responsible for the great majority of mismatched
empirical antibiotic prescriptions for suspected UTI at an urgent care clinic
among patients 70+ years old or with diabetes or urinary catheterization.
PMID- 29961841
TI - Accuracy and operational characteristics of Xpert HIV point-of-care testing at
birth and different time-points until week 6 in HIV-exposed neonates in Tanzania.
AB - Background: Point-of-care (PoC) systems for early infant diagnosis (EID) may
improve timely infant HIV management. However, experiences within African public
health settings are limited. Methods: We evaluated the accuracy and operational
feasibility of the Xpert HIV-1 Qual system for PoC-EID testing from fresh and
dried blood spots (DBS) whole blood samples at obstetric health facilities in
Tanzania at birth, and weeks 1, 2, 3 and 6 postpartum in HIV-exposed infants.
Test results were confirmed using TaqMan DBS HIV-DNA and/or plasma HIV-RNA
testing. Results: At week 6, 15 (2.5%) out of 614 infants were diagnosed with
HIV; 10 (66.7%) of them at birth with a median HIV-RNA of 4570 copies/ml. At
birth, the Xpert-PoC and Xpert-DBS was 100% sensitive (95%CI PoC: 69.2-100%, DBS:
66.4-100%) and also 100% specific (PoC: 92.1-100%, DBS: 88.4-100%). Five infants
with intra/postpartum HIV-infection (median HIV-RNA 1.160.000 copies/mL) were all
correctly diagnosed by Xpert by week three. In two cases, Xpert-PoC testing
correctly identified HIV infection when DBS tests (Xpert and TaqMan) were
negative suggesting a greater sensitivity. In two infants with confirmed HIV at
birth, all HIV tests were negative at week six, possibly because of viral
suppression under nevirapine prophylaxis. Problems were reported in 183/2736
(6.7%) of Xpert-PoC tests, mostly related to power cuts (57.9%). Conclusions: We
demonstrated excellent Xpert HIV-1 Qual performance and good operational
feasibility for PoC-EID testing at obstetric health facilities. Week 6
sensitivity issues were possibly related to nevirapine prophylaxis, supporting
additional birth PoC-EID testing to avoid under diagnosis.
PMID- 29961842
TI - Experimenting with reproducibility: a case study of robustness in bioinformatics.
AB - Reproducibility has been shown to be limited in many scientific fields. This
question is a fundamental tenet of scientific activity, but the related issues of
reusability of scientific data are poorly documented. Here, we present a case
study of our difficulties in reproducing a published bioinformatics method even
though code and data were available. First, we tried to re-run the analysis with
the code and data provided by the authors. Second, we reimplemented the whole
method in a Python package to avoid dependency on a MATLAB license and ease the
execution of the code on a high-performance computing cluster. Third, we assessed
reusability of our reimplementation and the quality of our documentation, testing
how easy it would be to start from our implementation to reproduce the results.
In a second section, we propose solutions from this case study and other
observations to improve reproducibility and research efficiency at the individual
and collective levels.While finalizing our code, we created case-specific
documentation and tutorials for the associated Python package StratiPy. Readers
are invited to experiment with our reproducibility case study by generating the
two confusion matrices (see more in section "Robustness: from MATLAB to Python,
language and organization"). Here, we propose two options: a step-by-step process
to follow in a Jupyter/IPython notebook or a Docker container ready to be built
and run.
PMID- 29961844
TI - Erratum to Development and Validation of a Confocal Laser Endomicroscopy-Based
Score for In Vivo Assessment of Mucosal Healing in Ulcerative Colitis Patients.
PMID- 29961843
TI - Rapid and Extensive Expansion in the U.S. of a New Multidrug-Resistant
Escherichia coli Clonal Group, Sequence Type ST1193.
AB - We describe the rapid and ongoing emergence across multiple US cities of a new
multidrug-resistant E. coli clone - ST1193, resistant to fluoroquinolones (100%),
trimethoprim/sulfamethoxazole (55%) and tetracycline (53%). ST1193 is associated
with younger adults (age < 40 years) and currently comprises a quarter of
fluoroquinolone-resistant clinical E. coli urine isolates.
PMID- 29961845
TI - On "Clinical Practice Guideline for Physical Therapy Assessment and Treatment in
Patients With Nonspecific Neck Pain," Bier JD, Scholten-Peeters WGM, Staal JB, et
al. Phys Ther. 2018;98:162-171.
PMID- 29961846
TI - AMBIENT DOSE EQUIVALENT RECEIVED AT 15 MV LINAC ENVIRONMENTS DUE TO PHOTONEUTRONS
CONTAMINATION.
AB - Mapping of the photoneutron spectrum and flux performed at several positions over
the treatment table of a 15 MV medical linac. Neutron activation technique has
been applied to obtain the neutron spectra in the mixed gamma -n field. Thick
foils have been used due to the low neutron flux and the measurements were
unfolded using the MINUIT minimizer. GEANT4 code simulations have been performed
to reproduce the photoneutrons' spectrum and estimate the flux along the
treatment table. The mixed radiation field around medical linear accelerator was
evaluated and the variation of the ambient dose equivalent over the treatment
table was estimated. Photoneutrons' ambient dose equivalent inside the
irradiation field estimated as 0.56 +/- 0.05 while the peripheral as 0.42 +/-
0.04 mSv Gy-1. The effective dose inside the irradiation field is ranged between
0.004 and 0.049 while the peripheral up to 0.035 mSv Gy-1.
PMID- 29961847
TI - Physical Impairments Associated With Post-Intensive Care Syndrome: Systematic
Review Based on the World Health Organization's International Classification of
Functioning, Disability and Health Framework.
AB - Background: Post-intensive care syndrome (PICS) is a constellation of new or
worsening impairments in physical, mental, or cognitive abilities or a
combination of these in individuals who have survived critical illness requiring
intensive care. Purpose: The 2 purposes of this systematic review were to
identify the scope and magnitude of physical problems associated with PICS during
the first year after critical illness and to use the World Health Organization's
International Classification of Functioning, Disability and Health (ICF)
framework to elucidate impairments of body functions and structures, activity
limitations, and participation restrictions associated with PICS. Data Sources:
Ovid MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register
of Controlled Trials (CENTRAL), PubMed, CINAHL Plus with Full Text (EBSCO), Web
of Science, and Embase were searched from inception until March 7, 2017. Study
Selection: Two reviewers screened titles, abstracts, and full text to
independently determine study eligibility based on inclusion and exclusion
criteria. Data Extraction: Study methodological quality was assessed using the
Newcastle-Ottawa Scale. Data describing study methods, design, and participant
outcomes were extracted. Data Synthesis: Fifteen studies were eligible for
review. Within the first year following critical illness, people who had received
intensive care experienced impairments in all 3 domains of the ICF (body
functions and structures, activity limitations, and participation restrictions).
These impairments included decreased pulmonary function, reduced strength of
respiratory and limb muscles, reduced 6-minute walk test distance, reduced
ability to perform activities of daily living and instrumental activities of
daily living, and reduced ability to return to driving and paid employment.
Limitations: The inclusion of only 15 observational studies in this review may
limit the generalizability of the findings. Conclusions: During the first year
following critical illness, individuals with PICS experienced physical
impairments in all 3 domains of the ICF.
PMID- 29961848
TI - Community-based Malaria Screening and Treatment for Pregnant Women Receiving
Standard Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine: A
Multicenter (The Gambia, Burkina Faso, and Benin) Cluster-randomized Controlled
Trial.
AB - Background: We investigated whether adding community scheduled malaria screening
and treatment (CSST) with artemether-lumefantrine by community health workers
(CHWs) to standard intermittent preventive treatment in pregnancy with
sulfadoxine-pyrimethamine (IPTp-SP) would improve maternal and infant health.
Methods: In this 2-arm cluster-randomized, controlled trial, villages in Burkina
Faso, The Gambia, and Benin were randomized to receive CSST plus IPTp-SP or IPTp
SP alone. CHWs in the intervention arm performed monthly CSST during pregnancy.
At each contact, filter paper and blood slides were collected, and at delivery, a
placental biopsy was collected. Primary and secondary endpoints were the
prevalence of placental malaria, maternal anemia, maternal peripheral infection,
low birth weight, antenatal clinic (ANC) attendance, and IPTp-SP coverage.
Results: Malaria infection was detected at least once for 3.8% women in The
Gambia, 16.9% in Benin, and 31.6% in Burkina Faso. There was no difference
between study arms in terms of placenta malaria after adjusting for birth season,
parity, and IPTp-SP doses (adjusted odds ratio, 1.06 [95% confidence interval,
.78-1.44]; P = .72). No difference between the study arms was found for
peripheral maternal infection, anemia, and adverse pregnancy outcomes. ANC
attendance was significantly higher in the intervention arm in Burkina Faso but
not in The Gambia and Benin. Increasing number of IPTp-SP doses was associated
with a significantly lower risk of placenta malaria, anemia at delivery, and low
birth weight. Conclusions: Adding CSST to existing IPTp-SP strategies did not
reduce malaria in pregnancy. Increasing the number of IPTp-SP doses given during
pregnancy is a priority. Clinical Trials Registration: NCT01941264;
ISRCTN37259296.
PMID- 29961850
TI - Personality and long-term health-related benefits.
AB - Background: Although it is well documented that non-medical factors, like
educational level, are associated with sick leave and disability pensioning, the
role of personality has only been studied to a limited degree. Aims: To examine
how normal personality traits (as measured by 'The Big Five') are associated with
long-term sick leave and disability pensioning. Methods: In 2008, a sample of
Norwegian women participating in the population-based Tracking Opportunities and
Problems (TOPP) study were assessed for personality traits. Three years later the
women reported on their job status and any episodes of sick leave and disability
pensioning over the previous 6 months. Using logistic regression analyses, we
examined the association between standardized measures of personality traits and
any episodes of long-term sick leave and disability pensioning. Results: Three
hundred and sixty-four women were included in the analyses (40% of those
invited). One standard level increase in neuroticism was significantly associated
with disability pensioning with an odds ratio (OR) of 2.07 (95% confidence
interval [CI]: 1.38-3.10). In contrast, an increase in extroversion and
conscientiousness was negatively associated with disability pensioning with ORs
of 0.59 (0.39-0.90) and 0.65 (0.43-0.99), respectively. For long-term sick leave,
there were no significant associations, although the trends in the estimates were
similar. Conclusions: Personality is strongly associated with disability
pensioning, but not with long-term sick leave. In particular, high neuroticism,
low extroversion and low conscientiousness seem to increase the risk for
disability pensioning. Initiatives aimed to reduce the prevalence of disability
pensioning should take personality traits into account.
PMID- 29961849
TI - KREAP: an automated Galaxy platform to quantify in vitro re-epithelialization
kinetics.
AB - Background: In vitro scratch assays have been widely used to study the influence
of bioactive substances on the processes of cell migration and proliferation that
are involved in re-epithelialization. The development of high-throughput
microscopy and image analysis has enabled scratch assays to become compatible
with high-throughput research. However, effective processing and in-depth
analysis of such high-throughput image datasets are far from trivial and require
integration of multiple image processing and data extraction software tools.
Findings: We developed and implemented a kinetic re-epithelialization analysis
pipeline (KREAP) in Galaxy. The KREAP toolbox incorporates freely available image
analysis tools and automatically performs image segmentation and feature
extraction of each image series, followed by automatic quantification of cells
inside and outside the scratched area over time. The enumeration of infiltrating
cells over time is modeled to extract three biologically relevant parameters that
describe re-epithelialization kinetics. The output of the tools is organized,
displayed, and saved in the Galaxy environment for future reference. Conclusions:
The KREAP toolbox in Galaxy provides an open-source, easy-to-use, web-based
platform for reproducible image processing and data analysis of high-throughput
scratch assays. The KREAP toolbox could assist a broad scientific community in
the discovery of compounds that are able to modulate re-epithelialization
kinetics.
PMID- 29961852
TI - Improving the visualization, interpretation and analysis of two-sample summary
data Mendelian randomization via the Radial plot and Radial regression.
AB - Background: data furnishing a two-sample Mendelian randomization (MR) study are
often visualized with the aid of a scatter plot, in which single-nucleotide
polymorphism (SNP)-outcome associations are plotted against the SNP-exposure
associations to provide an immediate picture of the causal-effect estimate for
each individual variant. It is also convenient to overlay the standard inverse
variance weighted (IVW) estimate of causal effect as a fitted slope, to see
whether an individual SNP provides evidence that supports, or conflicts with, the
overall consensus. Unfortunately, the traditional scatter plot is not the most
appropriate means to achieve this aim whenever SNP-outcome associations are
estimated with varying degrees of precision and this is reflected in the
analysis. Methods: We propose instead to use a small modification of the scatter
plot-the Galbraith Radial plot-for the presentation of data and results from an
MR study, which enjoys many advantages over the original method. On a practical
level, it removes the need to recode the genetic data and enables a more
straightforward detection of outliers and influential data points. Its use
extends beyond the purely aesthetic, however, to suggest a more general modelling
framework to operate within when conducting an MR study, including a new form of
MR-Egger regression. Results: We illustrate the methods using data from a two
sample MR study to probe the causal effect of systolic blood pressure on coronary
heart disease risk, allowing for the possible effects of pleiotropy. The Radial
plot is shown to aid the detection of a single outlying variant that is
responsible for large differences between IVW and MR-Egger regression estimates.
Several additional plots are also proposed for informative data visualization.
Conclusions: The Radial plot should be considered in place of the scatter plot
for visualizing, analysing and interpreting data from a two-sample summary data
MR study. Software is provided to help facilitate its use.
PMID- 29961853
TI - MrBait: Universal identification and design of targeted-enrichment capture
probes.
AB - Motivation: It is a non-trivial task to identify and design capture probes
("baits") for the diverse array of targeted-enrichment methods now available
(e.g. ultra-conserved elements, anchored hybrid enrichment, RAD-capture). This
often involves parsing large genomic alignments, followed by multiple steps of
curating candidate genomic regions to optimize targeted information content (e.g.
genetic variation), and to minimize potential probe dimerization and non-target
enrichment. Results: In this context, we developed MrBait, a user-friendly,
generalized software pipeline for identification, design, and optimization of
targeted-enrichment probes across a range of target-capture paradigms. MrBait is
an open-source codebase that leverages native parallelization capabilities in
Python and mitigates memory usage via a relational-database back-end. Numerous
filtering methods allow comprehensive optimization of designed probes, including
built-in functionality that employs BLAST, similarity-based clustering, and a
graph-based algorithm that 'rescues' failed probes. Availability: Complete code
for MrBait is available on GitHub (https://github.com/tkchafin/mrbait), and is
also available with all dependencies via one-line installation using the conda
package manager. Online documentation describing installation and runtime
instructions can be found at: https://mrbait.readthedocs.io.
PMID- 29961854
TI - Different twig litter (Salix caprea) diameter does affect microbial community
activity and composition but not decay rate.
AB - Small twigs represent a substantial input of organic carbon into forest soils,
but potential influencing factors on their decomposition have rarely been
investigated. Here, we studied potential effects of twig size on decomposition
and associated composition and activity of microbial communities during
decomposition. Because the surface area for microbial colonization and the volume
of accessible substrate increases with decreasing twig size, we hypothesized that
twig size affects both microbial community and decomposition rate. Litterbags
with twigs (Salix caprea) of two different diameters were placed within the
litter layer and consecutively collected over a seven-year period. We determined
the mass loss and microbial measures after each sampling event. The observed
microbial parameters suggested a faster microbial colonization of thin twigs,
where the proportion of bacteria was higher than in thick twigs. The development
of the microbial community in thick twigs was more gradual and the proportion of
fungi was higher. Despite this differential and successional development of
microbial communities (and against our hypothesis), the mass loss among different
twig diameters did not differ after our seven-year experiment, indicating that
surface-to-volume ratios, though a primary control on microbial succession, may
have limited predictive power for twig decomposition rates.
PMID- 29961855
TI - Pioneer Paper: Pioneers in Pediatric Psychology: The Enduring Value of Learning
to "Think Like a Psychologist".
PMID- 29961856
TI - Toxoplasma gondii rhoptry protein38 (TgROP38) affects parasite invasion, egress,
and induces IL-18 secretion during early infection.
AB - Toxoplasma rhoptry protein 38 (TgROP38) is a new active kinase that modulates
host cell signal transduction and TgROP38 expression shows strain-specificity and
stage-specificity in different isolates. In the present study, we overexpressed
ROP38 in the RH and prugniaud (PRU) strain (RH+rop38II and PRU+rop38II),
disrupted ROP38 (PRUDeltaROP38) in the PRU strain, complemented the ROP38
(PRUDeltaROP38comp+) in the PRUDeltaROP38 strain, and compared phenotypes of gene
edited and parental strains. We found that knockout of ROP38 led to increased
proliferation (P < 0.01) and invasion (P < 0.01) ability of the parasite.
However, intraperitoneal infection with 1000 tachyzoites, PRUDeltaROP38 showed
almost no virulent to mice compared with PRU (P < 0.01). Mice infected with low
dose of PRU parasites produced higher levels of IL-18 and IL-1beta compared with
those infected with the PRUDeltaROP38 parasites during early days (P < 0.01). IL
18 produced by the PRU-infected group was significantly higher than that of the
PRUDeltaROP38-infected group in vitro (P < 0.01). These phenomena may be related
to the involvement of TgROP38 in the regulation of TgProfilin (TgPRF) protein,
which could be recognized by host Toll-like receptor 11 and 12 (TLR11 and TLR12),
an activation of host immune response. We also found that TgPRF expression was
obviously decreased in PRUDeltaROP38, which was related to the cytokines
production in mice model. These findings reveal an intriguing biological function
of ROP38 in the RH and PRU toxoplasma, which may provide us with some clues of
the existence of this protein in other isolates.
PMID- 29961857
TI - Attraction of Ceratitis capitata (Diptera: Tephritidae) Sterile Males to
Essential Oils: The Importance of Linalool.
AB - Small cage and wind tunnel bioassays were used to understand the role of volatile
chemicals found in ginger root oil and other essential oils in the attraction of
sterile male Mediterranean fruit flies, Ceratitis capitata (Wiedemann) (Diptera:
Tephritidae). Small cage bioassays found that both a 10 component blend
(geraniol, linalool, beta-myrcene, limonene, alpha-pinene, beta-pinene, beta
caryophyllene, terpinen-4-ol, alpha-terpineol, and alpha-humulene) and a 4
component subset of that blend (geraniol, linalool, beta-myrcene and limonene)
were more attractive than paired mineral oil controls. Both blends were equally
attractive as ginger root oil and each other. Deletion studies, which tested all
3 component blends, found decreased attraction when linalool was deleted from the
4 component blend. Linalool alone attracted an equal percentage of flies as the 4
component blend, confirming that this chemical was responsible primarily for
attraction to ginger root oil. Wind tunnel bioassays confirmed previous studies
that panel traps baited with ginger root oil captured more flies than traps
baited with manuka oil. Addition of linalool to manuka oil resulted in capture
equal to ginger root oil, and addition of linalool to ginger root oil resulted in
capture of more flies than ginger root alone. The results of this study will
allow a better understanding of the role of individual plant-based chemicals in
the attraction of male C. capitata.
PMID- 29961858
TI - Reining in the QTc: reducing the risk of Torsades de Pointes across a major
health system.
AB - Hospitalized patients have a high prevalence of prolonged QTc and are a high-risk
population for Torsades de Pointes (TdP). One modifiable risk factor for TdP is
the use of QT prolonging drugs. Electronically alerting providers who are
ordering QT prolonging drugs in at-risk patients may help to achieve safer
prescribing practices. Our previous study decreased inappropriate prescription of
IV haloperidol by 36% using a targeted "smart" electronic alert. We wanted to
assess an approach to expanding this type of electronic alert to commonly used QT
prolonging medications and evaluate how this would affect prescribing practice.
This retrospective cohort study evaluated the impact of these alerts for 12
frequently prescribed high-risk medications across a major health system. Between
October 2016 and June 2017, a total of 6453 alerts fired and resulted in 3020
(46.8%) orders being cancelled by the provider. Our focused electronic alert
significantly decreased prescribing of QT prolonging medications in high-risk
patients.
PMID- 29961860
TI - Erratum to Targeting Mucosal Endothelin-A-Receptor Expression by Fluorescence
Endoscopy is Feasible to Detect and Characterize Colitis-Associated Cancer in
Mice.
PMID- 29961861
TI - ANNUAL PER-CAPITA DOSES OF THE JAPANESE FROM COSMIC RADIATION EXPOSURE IN
COMMERCIAL FLIGHTS.
AB - Annual per-capita aviation doses of the Japanese people from commercial flights
were calculated for 6 years period from 2009 (solar minimum) to 2014 (solar
maximum) using the flight routes provided by major Japanese airlines. For
international flights, the area other than Japan was separated to nine regions
and collective effective doses were estimated from the number of the Japanese
flyers to those regions multiplied by the calculated aviation route doses to
representing cities. Collective effective doses for domestic flights were
estimated as the products of the collective distances (man km) and the unit
distance route dose determined from three major routes. The flyer-average, annual
per-capita dose from the international flights was estimated as 54 MUSv and one
flight average dose from the domestic flights was 1.7 MUSv. As the Japanese
population average, the annual per-capita dose was 8.3 MUSv, of which nearly 90%
was from the international flights.
PMID- 29961859
TI - Acquisition of Multidrug-Resistant Human Immunodeficiency Virus Type 1 Infection
in a Patient Taking Preexposure Prophylaxis.
AB - We report a case indicating that acquisition of multidrug-resistant human
immunodeficiency (HIV) virus type 1 during preexposure prophylaxis with
combination tenofovir disoproxil fumarate and emtricitabine or evolution of
resistance after HIV seroconversion remains a risk.
PMID- 29961862
TI - V-Y Flap in Second Stage Release for the Lower Pole Following Autologous Ear
Reconstruction.
PMID- 29961864
TI - Corrigendum.
PMID- 29961863
TI - Sex differences in cardiac arrhythmia: a consensus document of the European Heart
Rhythm Association, endorsed by the Heart Rhythm Society and Asia Pacific Heart
Rhythm Society.
PMID- 29961865
TI - As Long as the Breath Lasts: In Utero Exposure to Ramadan and the Occurrence of
Wheezing in Adulthood.
AB - While prenatal exposure to Ramadan has been shown to be negatively associated
with general physical and mental health, studies on specific organs remain
scarce. In this study, we explored whether Ramadan exposure during pregnancy
affects the occurrence of wheezing, a main symptom of obstructive airway disease.
Using data from the Indonesian Family Life Survey collected between 1997 and 2008
(waves 2-4), we compared wheezing occurrence among adult Muslims who had been in
utero during Ramadan with that in adult Muslims who had not been in utero during
Ramadan. Wheezing prevalence was higher among adult Muslims who had been in utero
during Ramadan, independent of the pregnancy phase in which the exposure to
Ramadan occurred. Moreover, this association tended to increase with age, being
strongest among those aged about 45 years or older. This is in line with fetal
programming theory, suggesting that impacts of in utero exposures often manifest
only after reproductive age. Particularly strong associations were detected for
smokers. The respiratory system of prenatally exposed Muslims thus seems to
perform worse in mitigating later ex utero harmful influences such as smoking.
This study suggests that exposure to Ramadan during pregnancy may have lasting
consequences for adult lung functionality.
PMID- 29961866
TI - Unraveling the role of low-frequency mutated genes in breast cancer.
AB - Motivation: Breast cancer is the most commonly diagnosed malignancy in women and
the second cause of cancer death in developed countries. While advancements in
early detection and therapeutic options have led to a significant decrease in
mortality, response to treatment is affected by the genetic heterogeneity of the
disease. Recent genome-wide DNA mutation analyses revealed the existence of
hundreds of low-frequency mutated genes, in addition to known cancer drivers: a
finding that is prompting research into the impact of these genes on the
pathogenesis of the disease. Results: Herein, we describe a strategy towards the
characterization of the role of low-frequency mutated genes in breast cancer.
Through the combined analyses of publicly available gene expression and
mutational datasets, we identified several Cancer Gene Modules (CMs) that we re
organized in Gene Regulatory Networks (GRN) enriched in low-frequency mutated
genes. Importantly, these low-frequency mutated genes were mutually exclusive
with known cancer drivers. Finally, we provide evidence that gene expression
analysis of these mutated GRNs can predict resistance/sensitivity to
chemotherapeutic drugs for breast cancer treatment. Availability: Datasets are
available at https://www.ncbi.nlm.nih.gov/geo/ and at
https://www.ebi.ac.uk/ega/datasets/. Molecular signatures and GSEA software are
available at http://www.gsea-msigdb.org/gsea/index.jsp. Source codes are
available at https://github.com/EleonoraLusito/Reverse_Engineering_BC_GRNs.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29961867
TI - Early and long-term outcomes for patients undergoing reoperative aortic root
replacement.
AB - OBJECTIVES: There are limited data on aortic root replacement (ARR) in patients
with previous cardiac surgery. We analysed short-term and long-term results for
patients with ARR after previous cardiac surgery. METHODS: From September 1995 to
April 2015, 130 patients underwent reoperative ARR. Fifty patients had undergone
ARR previously (Group I), and 80 had been treated by isolated aortic valve repair
or replacement (Group II). The primary indications for surgery were active
endocarditis in 65 patients (50%), aneurysmatic root dilatation in another 37
(28.5%) and valve failure in 27 (20.8%). RESULTS: Overall hospital mortality was
10% (n = 13). Survival at 10 and 15 years was 59.4% and 40.6%, respectively.
Survival at 10 and 15 years was 71.5% and 62.5% in Group I and 56.2% and 35.4% in
Group II, respectively (P = 0.14). Survival was significantly worse in patients
operated for active endocarditis (23.7% vs 56.4% at 15 years; P < 0.001).
Inferior 15-year survival was also observed for patients requiring concomitant
surgery for cardiac comorbidities (10.5% vs 48.7%; P = 0.003) and in the elderly
(>=60 years; 26.8% vs 59.5%; P < 0.001). Ten-year survival was best in patients
after valve-preserving root replacement (100%). Multivariable analysis revealed
age, active endocarditis and concomitant surgery for cardiac comorbidities as
risk factors for death. CONCLUSIONS: ARR after previous cardiac surgery can be
performed with reasonable short-term and long-term survival. It is inferior in
patients with active endocarditis or cardiac comorbidities and in the elderly. In
these scenarios, less invasive procedures may be considered where applicable.
PMID- 29961868
TI - Leukocyte Telomere Length and All-Cause Mortality: A Between-Within Twin Study
With Time-Dependent Effects Using Generalized Survival Models.
AB - Although previous studies examining leukocyte telomere length (LTL) and all-cause
mortality controlled for several confounders, the observed association could be
biased due to unmeasured confounders, including familial factors. We aimed to
examine the association of LTL with all-cause mortality in a Swedish twin sample
while adjusting for familial factors and allowing for time-dependent effects. A
total of 366 participants (174 twin pairs and 18 individuals) were recruited from
the Swedish Twin Registry. LTL was assessed using the Southern blot method. All
cause mortality data were obtained through linkage with the Swedish Population
Registry, updated through November 15, 2017. To control for familial factors
within twin pairs, we applied a between-within shared frailty model based on
generalized survival models. Overall, 115 (31.4%) participants were men and 251
(68.6%) were women. The average age of the study participants when blood was
drawn was 79.1 years, and follow-up duration ranged from 10 days to 25.7 years
(mean = 10.2 years). During the follow-up period, 341 (93.2%) participants died.
Shorter LTL was associated with higher mortality rates when controlling for
familial factors in the between-within shared frailty model. We found significant
time-dependent effects of LTL on all-cause mortality, where the mortality rate
ratios were attenuated with increasing age.
PMID- 29961869
TI - Cardiac computed tomography and magnetic resonance imaging vs. transoesophageal
echocardiography for diagnosing left atrial appendage thrombi.
AB - Aims: Transoesophageal echocardiography (TOE) is the gold standard for
identification of left atrial appendage (LAA) thrombi. However, TOE is semi
invasive and cannot be performed in certain patients. Left atrial appendage
thrombi can also be identified by cardiac computed tomography (CCT) and cardiac
magnetic resonance imaging (CMR); however, the diagnostic performance of these
techniques vs. TOE is unclear. Methods and results: We performed a systematic
review and meta-analysis of 22 CCT and 4 CMR studies comparing diagnostic
performance to TOE for identification of LAA thrombi. Meta-regression was
performed to determine whether expected sensitivity and specificity differed
between early and delayed image acquisition protocols for CCT vs. TOE and between
CCT and CMR. Cardiac computed tomography demonstrated sensitivity and specificity
of 0.99 [confidence interval (CI 0.93-1.00)] and 0.94 (CI 0.90-0.97) respectively
vs. TOE. A subgroup analysis comparing early vs. delayed protocol CCT imaging was
performed showing no significant differences in sensitivity (P-value = 0.17)
however improved specificity of the delayed imaging protocols (P-value = 0.04).
Cardiac magnetic resonance imaging demonstrated sensitivity and specificity of
0.80 (CI 0.63-0.91) and 0.98 (CI 0.97-0.99), respectively when compared to TOE.
There was no significant difference in sensitivity or specificity between CMR and
CCT (P-values 0.996 and 0.484, respectively). Conclusion: Cardiac computed
tomography and CMR had good to excellent sensitivity and specificity vs. TOE.
Further, there was no significant difference in the sensitivity and specificity
of CCT vs. CMR, suggesting that both modalities can be considered reasonable
alternatives to TOE in the identification of LAA thrombi. Cardiac magnetic
resonance imaging may be especially beneficial when TOE and CCT cannot be
performed.
PMID- 29961870
TI - De novo variants in GABRA2 and GABRA5 alter receptor function and contribute to
early-onset epilepsy.
AB - GABAA receptors are ligand-gated anion channels that are important regulators of
neuronal inhibition. Mutations in several genes encoding receptor subunits have
been identified in patients with various types of epilepsy, ranging from mild
febrile seizures to severe epileptic encephalopathy. Using whole-genome
sequencing, we identified a novel de novo missense variant in GABRA5 (c.880G > C,
p.V294L) in a patient with severe early-onset epilepsy and developmental delay.
Targeted resequencing of 279 additional epilepsy patients identified 19 rare
variants from nine GABAA receptor genes, including a novel de novo missense
variant in GABRA2 (c.875C > A, p.T292K) and a recurrent missense variant in
GABRB3 (c.902C > T, p.P301L). Patients with the GABRA2 and GABRB3 variants also
presented with severe epilepsy and developmental delay. We evaluated the effects
of the GABRA5, GABRA2 and GABRB3 missense variants on receptor function using
whole-cell patch-clamp recordings from human embryonic kidney 293T cells
expressing appropriate alpha, beta and gamma subunits. The GABRA5 p.V294L variant
produced receptors that were 10-times more sensitive to GABA but had reduced
maximal GABA-evoked current due to increased receptor desensitization. The GABRA2
p.T292K variant reduced channel expression and produced mutant channels that were
tonically open, even in the absence of GABA. Receptors containing the GABRB3
p.P301L variant were less sensitive to GABA and produced less GABA-evoked
current. These results provide the first functional evidence that de novo
variants in the GABRA5 and GABRA2 genes contribute to early-onset epilepsy and
developmental delay, and demonstrate that epilepsy can result from reduced
neuronal inhibition via a wide range of alterations in GABAA receptor function.
PMID- 29961871
TI - The effect of a gene associated with retinoid-interferon-induced mortality 19
(GRIM-19) on STAT3-induced gene expression in renal carcinoma.
AB - This study aimed to investigate the exact regulatory mechanisms of retinoid
interferon-induced mortality 19 (GRIM-19) in renal carcinoma. Tumour tissue
samples from patients with renal carcinoma (n = 30, there were seven cases of
Stage I, eight cases of Stage II, eight cases of Stage III, seven cases of Stage
IV) and control subjects were selected from adjacent normal tissue (n = 10). Real
time quantitative PCR and western blotting were used to assess the level of GRIM
19, signal transducer and activator of transcription-3 (STAT3) and its downstream
molecules. CD31 was detected by immunohistochemistry. The MTT assay was used to
measure cell proliferation. The amount of apoptosis cells was analysed by Flow
cytometry. The results showed that expression of GRIM-19 was decreased in renal
carcinoma. However, in tumour tissue, STAT3 and its downstream signalling
molecules showed the higher expression compared with control. Overexpression of
GRIM-19, inhibited tumour growth apoptosis by mediating activators of STAT3
signal. In addition, interferon-beta and all-trans-retinoic acid inhibited the
renal carcinoma cell growth and induced apoptosis, and effect of drug
combinations was particularly evident. In conclusion, GRIM-19 expression is
associated with hyperactivation of STAT3-induced gene expression in renal
carcinoma.
PMID- 29961872
TI - Perioperative Cardiovascular Outcomes of Non-Cardiac Solid Organ Transplant
Surgery.
AB - Background: Perioperative cardiovascular outcomes of transplant surgery are not
well defined. We evaluated the incidence of perioperative major cardiovascular
and cerebrovascular events (MACCE) after non-cardiac transplant surgery from a
large database of hospital admissions from the United States. Methods: Patients
>=18 years of age undergoing non-cardiac solid organ transplant surgery from 2004
to 2014 were identified from the Healthcare Cost and Utilization Project's (HCUP)
National Inpatient Sample (NIS). The primary outcome was perioperative MACCE,
defined as in-hospital death, myocardial infarction (MI), or ischemic stroke.
Results: A total of 49,978 hospitalizations for transplant surgery were
identified. Renal (67.3%), liver (21.6%), and lung (6.7%) transplantation were
the most common surgeries. Perioperative MACCE occurred in 1,539 transplant
surgeries (3.1%). Recipients of organ transplantation were more likely to have
perioperative MACCE in comparison to non-transplant, non-cardiac surgery (3.1%
vs. 2.0%, p < 0.001; adjusted OR [aOR] 1.29, 95% CI 1.22-1.36). MACCE after
transplant surgery were driven by increased mortality (1.7% vs. 1.1%, p < 0.001;
aOR 1.15, 95% CI 1.07-1.23) and MI (1.2% vs. 0.6%, p < 0.001; aOR 2.26, 95% CI
2.09-2.46) versus non-transplant surgery, with lower rates of stroke (0.3% vs.
0.5%, p < 0.001; aOR 0.56, 95% CI 0.47-0.65). Among patients hospitalized for
renal, liver, and lung transplantation, MACCE occurred in 1.7%, 5.6%, and 7.5%,
respectively, with no difference in the frequency of MI by surgery type.
Conclusions: Cardiovascular outcomes of transplant surgery vary by surgical
subtype and are largely driven by increased perioperative death and MI. Efforts
to reduce cardiovascular risks of non-cardiac organ transplant surgery are
necessary.
PMID- 29961873
TI - Transcriptome Characterization of Matched Primary Breast and Brain Metastatic
Tumors to Detect Novel Actionable Targets.
AB - Background: Breast cancer brain metastases (BrMs) are defined by complex
adaptations to both adjuvant treatment regimens and the brain microenvironment.
Consequences of these alterations remain poorly understood, as does their
potential for clinical targeting. We utilized genome-wide molecular profiling to
identify therapeutic targets acquired in metastatic disease. Methods: Gene
expression profiling of 21 patient-matched primary breast tumors and their
associated brain metastases was performed by TrueSeq RNA-sequencing to determine
clinically actionable BrM target genes. Identified targets were functionally
validated using small molecule inhibitors in a cohort of resected BrM ex vivo
explants (n = 4) and in a patient-derived xenograft (PDX) model of BrM. All
statistical tests were two-sided. Results: Considerable shifts in breast cancer
cell-specific gene expression profiles were observed (1314 genes upregulated in
BrM; 1702 genes downregulated in BrM; DESeq; fold change > 1.5, Padj < .05).
Subsequent bioinformatic analysis for readily druggable targets revealed
recurrent gains in RET expression and human epidermal growth factor receptor 2
(HER2) signaling. Small molecule inhibition of RET and HER2 in ex vivo patient
BrM models (n = 4) resulted in statistically significantly reduced proliferation
(P < .001 in four of four models). Furthermore, RET and HER2 inhibition in a PDX
model of BrM led to a statistically significant antitumor response vs control (n
= 4, % tumor growth inhibition [mean difference; SD], anti-RET = 86.3% [1176;
258.3], P < .001; anti-HER2 = 91.2% [1114; 257.9], P < .01). Conclusions: RNA-seq
profiling of longitudinally collected specimens uncovered recurrent gene
expression acquisitions in metastatic tumors, distinct from matched primary
tumors. Critically, we identify aberrations in key oncogenic pathways and provide
functional evidence for their suitability as therapeutic targets. Altogether,
this study establishes recurrent, acquired vulnerabilities in BrM that warrant
immediate clinical investigation and suggests paired specimen expression
profiling as a compelling and underutilized strategy to identify targetable
dependencies in advanced cancers.
PMID- 29961875
TI - Metabolomics of heat stress response in pig adipose tissue reveals alteration of
phospholipid and fatty acid composition during heat stress.
AB - To determine the effect of heat stress (HS) on adipose tissue metabolome, a
combination of liquid chromatography-mass spectrometry-based metabolomics
profiling approaches was applied to characterize changes of metabolite classes in
adipocytes differentiated in culture (in vitro) and mesenteric adipose tissue of
pigs exposed to HS (in vivo). Effect of HS on the composition of individual fatty
acids in cultured adipocytes, mesenteric adipose tissue, and serum of animals was
also investigated using gas chromatography analysis. In vitro, preadipocytes were
differentiated either under control (37 degrees C) or HS (41.5 degrees C)
temperature for 9 d. For the animal experiment, pigs were kept either in control
(Con) environment (20 degrees C) with ad libitum feed intake, HS (35 degrees C)
temperature with ad libitum feed intake (HS), or at 20 degrees C with pair
feeding to the HS pigs. In cultured cells, HS increased triglyceride and
decreased monoacylglycerol (P < 0.05) species accumulation compared with control.
Phosphatidylinositol and phosphatidylserine were increased by HS, whereas
phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol were
decreased relative to control (P < 0.05). Heat-stressed adipocytes in culture
also had higher concentrations of saturated (SFA) and monounsaturated fatty acids
(P < 0.05) relative to control. Pathways of proline and biotin metabolism were
elevated (P < 0.05) by HS in adipocytes. The metabolomics signatures in
adipocytes cultured under HS indicates that pathways centered around
diacylglycerol metabolism are impacted by HS. In adipose tissue from animals in
the HS treatment, there was increased (P < 0.05) abundance of 4,8
dimethylnonanoyl carnitine (P < 0.05). Heat-stressed animals also had higher (P <
005) serum linoleic, total polyunsaturated fatty acids, and decreased total SFA
than PF (P < 0.05). These results indicate that HS elevates lipogenic pathways
while suppressing fatty acid oxidation and demonstrate the usefulness of
metabolomics analysis as a tool for determining the impact of HS in pig tissues.
PMID- 29961876
TI - Risk of acute kidney injury following community prescription of antibiotics: self
controlled case series.
AB - Background: Development of acute kidney injury (AKI) following the use of
antibiotics such as sulphonamides, trimethoprim and aminoglycosides is a
frequently described phenomenon. More recently, an association between
fluoroquinolone use and AKI has been suggested. The aim of this study was to
evaluate the risk of AKI as an unintended consequence of commonly prescribed
antibiotics in a large community cohort using a method that fully adjusts for
underlying patient characteristics, including potential unmeasured confounders.
Methods: A self-controlled case study was conducted and included all individuals
aged 18 years and over in the Tayside region of Scotland who had a serum
creatinine measured between 1 January 2004 and 31 December 2012. AKI episodes
were defined using the Kidney Disease: Improving Global Outcomes definition. Data
on oral community-prescribed antibiotics (penicillins, cephalosporins,
fluoroquinolones, sulphonamides and trimethoprim, macrolides and nitrofurantoin)
were collected for all individuals. Incidence rate ratios (IRRs) for AKI
associated with antibiotic exposure versus time periods without antibiotic
exposure were calculated. Results: Combined use of sulphonamides, trimethoprim
and nitrofurantoin rose by 47% and incidence of community-acquired AKI rose by
16% between 2008 and 2012. During the study period 12 777 individuals developed
14 900 episodes of AKI in the community, of which 68% was AKI Stage 1, 16% Stage
2 and 16% Stage 3. The IRR of AKI during any antibiotic use was 1.16 [95%
confidence interval (CI) 1.10-1.23], and this was highest during sulphonamides or
trimethoprim use; IRR 3.07 (95% CI 2.81-3.35). Fluoroquinolone and nitrofurantoin
use was not associated with a significantly increased rate of AKI; IRR 1.13 (95%
CI 0.94-1.35) and 1.16 (95% CI 0.91-1.50), respectively. Conclusions: Incidence
of AKI rose by 16% between 2008 and 2012. In the same period the use of
sulphonamides, trimethoprim and nitrofurantoin increased by 47%. A significant
increased risk of AKI was seen with the use of sulphonamides and trimethoprim,
but not with fluoroquinolones or nitrofurantoin.
PMID- 29961877
TI - Root and cell hydraulic conductivity, apoplastic barriers and aquaporin gene
expression in barley (Hordeum vulgare L.) grown with low supply of potassium.
AB - Background and Aims: Limited supply of mineral nutrients often reduces plant
growth and transpirational water flow while increasing the ratio of water
absorbing root to water-losing shoot surface. This could potentially lead to an
imbalance between water uptake (too much) and water loss (too little). The aim of
the present study was to test whether, as a countermeasure, the hydraulic
properties (hydraulic conductivity, Lp) of roots decrease at organ and cell level
and whether any decreases in Lp are accompanied by decreases in the gene
expression level of aquaporins (AQPs) or increases in apoplastic barriers to
radial water movement. Methods: Barley plants were grown hydroponically on
complete nutrient solution, containing 2 mm K+ (100 %), or on low-K solution
(0.05 mm K+; 2.5 %), and analysed when they were 15-18 d old. Transpiration,
fresh weight, surface area, shoot water potential (psi), K and Ca concentrations,
root (exudation) and cortex cell Lp (cell pressure probe), root anatomy (cross
sections) and AQP gene expression (qPCR) were analysed. Key Results: The surface
area ratio of root to shoot increased significantly in response to low K. This
was accompanied by a small decrease in the rate of water loss per unit shoot
surface area, but a large (~50 %) and significant decrease in Lp at root and
cortex cell levels. Aquaporin gene expression in roots did not change
significantly, due to some considerable batch-to-batch variation in expression
response, though HvPIP2;5 expression decreased on average by almost 50 %.
Apoplastic barriers in the endodermis did not increase in response to low K.
Conclusions: Barley plants that are exposed to low K adjust to an increased ratio
of root (water uptake) to shoot (water loss) surface primarily through a decrease
in root and cell Lp. Reduced gene expression of HvPIP2;5 may contribute to the
decrease in Lp.
PMID- 29961874
TI - Global Ramifications of Dust and Sandstorm Microbiota.
AB - Dust and sandstorm events inject substantial quantities of foreign microorganisms
into global ecosystems, with the ability to impact distant environments. The
majority of these microorganisms originate from deserts and drylands where the
soil is laden with highly stress-resistant microbes capable of thriving under
extreme environmental conditions, and a substantial portion of them survive long
journeys through the atmosphere. This large-scale transmission of highly
resilient alien microbial contaminants raises concerns with regards to the
invasion of sensitive and/or pristine sink environments, and to human health
concerns exacerbated by increases in the rate of desertification. Further
increases in the transport of dust-associated microbiota could extend the spread
of foreign microbes to new ecosystems, increase their load in present sink
environments, disrupt ecosystem balance, and potentially introduce new pathogens.
Our present understanding of these microorganisms, their phylogenic affiliations
and functional significance, is insufficient to determine their impact. The
purpose of this review is to provide an overview of available data regarding dust
and sandstorm microbiota and their potential ramifications on human and ecosystem
health. We conclude by discussing current gaps in dust and sandstorm microbiota
research, and the need for collaborative studies involving high-resolution meta
omic approaches in conjunction with extensive ecological time-series studies to
advance the field towards an improved and sufficient understanding of these
invisible atmospheric travelers and their global ramifications.
PMID- 29961878
TI - Increasing population height and risk of incident atrial fibrillation: the
Copenhagen City Heart Study.
AB - Aims: The incidence of atrial fibrillation (AF) has increased significantly over
the last decades. Population height is changing in many countries. Height is an
important risk factor for AF. The aim of the present study was to assess the role
of changes in population height in the increased risk of AF. Methods and results:
The Copenhagen City Heart Study comprises 18 852 randomly selected men and women
aged 20-93 years, studied in four separate cross-sectional surveys in 1976-78,
1981-83, 1991-94, and 2001-03, including physical examination, electrocardiogram
(ECG), and standard questionnaires. Hospitalization and mortality data were
collected from public registers. Prevalent AF was determined from ECGs and
incident AF from register diagnoses. During follow-up, age-standardized
prevalence of AF increased significantly from 1.35% to 2.11% in men and from
0.67% to 1.07% in women (P < 0.001). Incident AF increased four-fold in both men
and women [hazard ratio (HR) 4.16, 95% confidence interval (CI) 3.27-5.29; P <
0.001]. In multivariable Fine and Gray subdistribution hazards regression
analyses, height was consistently an important risk factor for incident AF with
HRs between 1.35 (95% CI 1.10-1.66; P = 0.004) and 1.65 (95% CI 1.40-1.93; P <
0.001). Population height increased with 3.3 cm for men and 2.1 cm for women, and
population attributable risks for height was 20-30%. Conclusion: Height is a
powerful risk factor for AF. Adult height is attained at age 20, while AF
incidence occurs 50 years later. Given a causal relationship between height and
AF incidence, increased population height in Denmark will contribute to an
increase in AF occurrence for at least 25 more years.
PMID- 29961880
TI - Examining the Role of Neighborhood-Level Foreclosure in Smoking and Alcohol Use
Among Older Adults in the Multi-Ethnic Study of Atherosclerosis.
AB - The US Great Recession resulted in an alarming number of home foreclosures that
weakened the social and physical environment of thousands of neighborhoods. Few
studies have evaluated whether these neighborhood changes were related to changes
in individual behaviors. We examined the relationship between changes in
neighborhood-level home foreclosure within a quarter-mile (0.4-km) buffer of the
residence and changes in cigarette smoking and alcohol use among 3,807 adults
enrolled in the Multi-Ethnic Study of Atherosclerosis during 2005-2012, using
econometric individual-level fixed-effects models. Increases in neighborhood
level foreclosure were associated with small decreases in the number of
cigarettes smoked per day (mean difference = -0.08, 95% confidence interval:
0.11, -0.04) and small increases in the number of alcoholic beverages consumed
per week (mean difference = 0.11, 95% confidence interval: 0.05, 0.17).
Neighborhood-level foreclosure may not uniformly influence high-risk behaviors.
The impact of home foreclosure on adult drinking should be further explored,
given its potentially negative implications for health.
PMID- 29961879
TI - Spatial Patterns of Extensively Drug-Resistant Tuberculosis Transmission in
KwaZulu-Natal, South Africa.
AB - Background: Transmission is driving the global drug-resistant tuberculosis (TB)
epidemic; nearly three-quarters of drug-resistant TB cases are attributable to
transmission. Geographic patterns of disease incidence, combined with information
on probable transmission links, can define the spatial scale of transmission and
generate hypotheses about factors driving transmission patterns. Methods: We
combined whole-genome sequencing data with home Global Positioning System
coordinates from 344 participants with extensively drug-resistant (XDR) TB in
KwaZulu-Natal, South Africa, diagnosed from 2011 to 2014. We aimed to determine
if genomically linked (difference of <=5 single-nucleotide polymorphisms) cases
lived close to one another, which would suggest a role for local community
settings in transmission. Results: One hundred eighty-two study participants were
genomically linked, comprising 1084 case-pairs. The median distance between case
pairs' homes was 108 km (interquartile range, 64-162 km). Between-district, as
compared to within-district, links accounted for the majority (912/1084 [84%]) of
genomic links. Half (526 [49%]) of genomic links involved a case from Durban, the
urban center of KwaZulu-Natal. Conclusions: The high proportions of between
district links with Durban provide insight into possible drivers of province-wide
XDR-TB transmission, including urban-rural migration. Further research should
focus on characterizing the contribution of these drivers to overall XDR-TB
transmission in KwaZulu-Natal to inform design of targeted strategies to curb the
drug-resistant TB epidemic.
PMID- 29961881
TI - Characteristics of Neighbourhoods with High Incidence of Out-of-Hospital Cardiac
Arrest and Low Bystander Cardiopulmonary Resuscitation Rates in England.
PMID- 29961883
TI - Temporal dynamics and risk factors for bloodstream infection with extended
spectrum beta-lactamase-producing bacteria in previously colonized individuals:
National population-based cohort study.
AB - Background: Little is known of the long-term risk of bloodstream infection (BSI)
with extended spectrum beta-lactamase producing Enterobacteriaceae (EPE) in
previously colonized individuals. We investigated EPE-BSI risk and associated
risk factors during 6 years following EPE colonization. Methods: We performed a
population-based cohort study in Sweden using national health registers. Subjects
were followed from their first EPE finding in feces (n=5513) or urine (n=17189).
The effect of co-morbidity, sociodemography, and outpatient antibiotic
dispensation on EPE-BSI risk was assessed. The EPE-BSI risk was compared to that
of 45161 matched population-based reference subjects. Results: The cumulative 6
year EPE-BSI incidence was 3.8%, 1.6% and 0.02% in the urine, feces and reference
cohorts, respectively. The incidence decreased exponentially during the first 6
12 months. Among EPE-exposed subjects urological disorders were associated with
the highest adjusted cause-specific hazard ratio (aCSHR) for subsequent EPE-BSI:
3.40 (2.47-4.69). The aCSHRs were between 1.62-2.20 for male sex,
immunosuppression, diabetes, malignancy, lung disease, baseline urine source, and
Klebsiella pneumoniae compared to Escherichia coli baseline sample. Antibiotics
with selective activity against gram-negative bacilli but mostly not EPE
(trimethoprim-sulfamethoxazole, fluoroquinolones, oral cephalosporins and
penicillins with extended spectrum), and pivmecillinam were associated with a two
fold increased EPE-BSI risk during three months after antibiotic dispensation in
EPE-colonized subjects. Conclusions: EPE in urine or feces is a substantial risk
factor for subsequent EPE-BSI but the risk declines rapidly during the first year
after detection. In EPE colonized individuals specific risk factors can be used
to identify subgroups for targeted interventions such as eradication therapy.
PMID- 29961882
TI - Long-term exposure to sensory feed additives during the gestational and postnatal
periods affects sows' colostrum and milk sensory profiles, piglets' growth, and
feed intake.
AB - This study investigated the effect of feed supplementation in sows and/or their
progeny with 2 sensory feed additives (FA1: limonene and cinnamaldehyde; FA2:
menthol, carvone, and anethole) on sows' feed intake, body weight, fat
deposition, and colostrum/milk composition, as well as piglets' feed intake
growth and feed efficiency from birth to slaughter at postnatal day 160 (PND160).
During the last third of gestation and the whole of lactation, sows were
subjected to a control diet (C) or the same diet containing FA1 or FA2 at 0.1% of
complete feed content. Colostrum/milk samples were taken at days 1, 14, and 28 of
lactation for gas chromatography-mass spectrometry analyses. After weaning, the
progeny was subjected to a control diet (C) or experimental diets with a
sweetener (0.015%) but no other additive (S), or to diets with a sweetener and
the additive FA1 (FA1S) or FA2 (FA2S). There was no effect of dietary treatment
on sows' feed intake, body weight, or adiposity (P > 0.15 for all), but the
sensory characteristics of their colostrum/milk were modified by the diet and
diet*time interaction. Limonene concentrations were higher in FA1 samples from
PND1 to PND28, whereas carvone and anethole concentrations were higher in FA2
samples from PND1 to PND28. The concentration of these 3 compounds increased with
time in the respective groups where they were mostly detected. Menthol
concentrations were higher in FA2 samples at PND14 and PND28, but there was no
time effect. Overall, cinnamaldehyde was always below the detection range.
Piglets born from FA1 and FA2 sows had higher body weight (P = 0.034 at PND160),
average daily gain (ADG; P = 0.036 for PND0-160), and average daily feed intake
(ADFI; P = 0.006 for PND28-160) than piglets born from C sows. Overall, piglets
that were never exposed to FA or only after weaning had lower ADG (P = 0.030 for
PND0-160) and ADFI (P = 0.016 for PND28-160) than piglets that were exposed to FA
only via the maternal diet, the condition combining both pre- and post-natal
exposure being intermediary. In conclusion, FA1 and FA2 provided to gestating and
lactating sows increased the progeny's feed intake and growth, suggesting
nutritional programming and/or sensory conditioning during the perinatal period.
Addition of FA only in the progeny's diet was not beneficial.
PMID- 29961885
TI - Corrigendum.
PMID- 29961884
TI - A new image-guided technique for intraoperative localization of lung small solid
nodules or ground-glass opacities with a self-expanding tract sealant device: a
preliminary experience.
AB - OBJECTIVES: The aim of this study was to evaluate a new self-expanding tract
sealant device, designed to prevent pneumothorax after computed tomography (CT)
guided lung biopsy, as an intraoperative marker for small pulmonary nodules or
ground-glass opacities during minimally invasive thoracic surgery. METHODS: Three
patients with pulmonary nodules underwent CT-guided biopsies in our radiology
department. During the same procedure, using a 19-gauge coaxial needle, a self
expanding tract sealant device was positioned in the lung nodule to be used not
only for the prevention of pneumothorax but also as an intraoperative marker. A
few days later, conventional thoracoscopic surgery was scheduled. A visual
examination was performed. The site of the deployment of the BioSentry device was
determined by checking for the proximal end of it beyond the visceral pleura.
Thoracoscopic wedge resections using endoscopic staplers were performed to
confirm histological characteristics, surgical margins and correct placement of
the plug. RESULTS: Three consecutive patients underwent CT-guided placement of
this self-expanding tract sealant device (BioSentry) before surgery, without
complications. The thoracoscopic resection was performed with success. The plug
was easy to visualize with the scope, and all removed nodules had surgical free
margins and the plug was correctly positioned in all patients. CONCLUSIONS: The
self-expanding tract sealant device was created for the reduction of pneumothorax
and chest tube placement rates after percutaneous lung biopsy. We used it for the
first time for intraoperative localization of peripheral small solid nodules or
ground-glass opacities with good results.
PMID- 29961886
TI - CHP1 reduction ameliorates spinal muscular atrophy pathology by restoring
calcineurin activity and endocytosis.
AB - Autosomal recessive spinal muscular atrophy (SMA), the leading genetic cause of
infant lethality, is caused by homozygous loss of the survival motor neuron 1
(SMN1) gene. SMA disease severity inversely correlates with the number of SMN2
copies, which in contrast to SMN1, mainly produce aberrantly spliced transcripts.
Recently, the first SMA therapy based on antisense oligonucleotides correcting
SMN2 splicing, namely SPINRAZATM, has been approved. Nevertheless, in type I SMA
affected individuals-representing 60% of SMA patients-the elevated SMN level may
still be insufficient to restore motor neuron function lifelong. Plastin 3 (PLS3)
and neurocalcin delta (NCALD) are two SMN-independent protective modifiers
identified in humans and proved to be effective across various SMA animal models.
Both PLS3 overexpression and NCALD downregulation protect against SMA by
restoring impaired endocytosis; however, the exact mechanism of this protection
is largely unknown. Here, we identified calcineurin-like EF-hand protein 1 (CHP1)
as a novel PLS3 interacting protein using a yeast-two-hybrid screen. Co
immunoprecipitation and pull-down assays confirmed a direct interaction between
CHP1 and PLS3. Although CHP1 is ubiquitously present, it is particularly abundant
in the central nervous system and at SMA-relevant sites including motor neuron
growth cones and neuromuscular junctions. Strikingly, we found elevated CHP1
levels in SMA mice. Congruently, CHP1 downregulation restored impaired axonal
growth in Smn-depleted NSC34 motor neuron-like cells, SMA zebrafish and primary
murine SMA motor neurons. Most importantly, subcutaneous injection of low-dose
SMN antisense oligonucleotide in pre-symptomatic mice doubled the survival rate
of severely-affected SMA mice, while additional CHP1 reduction by genetic
modification prolonged survival further by 1.6-fold. Moreover, CHP1 reduction
further ameliorated SMA disease hallmarks including electrophysiological defects,
smaller neuromuscular junction size, impaired maturity of neuromuscular junctions
and smaller muscle fibre size compared to low-dose SMN antisense oligonucleotide
alone. In NSC34 cells, Chp1 knockdown tripled macropinocytosis whereas clathrin
mediated endocytosis remained unaffected. Importantly, Chp1 knockdown restored
macropinocytosis in Smn-depleted cells by elevating calcineurin phosphatase
activity. CHP1 is an inhibitor of calcineurin, which collectively
dephosphorylates proteins involved in endocytosis, and is therefore crucial in
synaptic vesicle endocytosis. Indeed, we found marked hyperphosphorylation of
dynamin 1 in SMA motor neurons, which was restored to control level by the
heterozygous Chp1 mutant allele. Taken together, we show that CHP1 is a novel SMA
modifier that directly interacts with PLS3, and that CHP1 reduction ameliorates
SMA pathology by counteracting impaired endocytosis. Most importantly, we
demonstrate that CHP1 reduction is a promising SMN-independent therapeutic target
for a combinatorial SMA therapy.
PMID- 29961887
TI - Things Are Changing so Fast: Integrative Technology for Preserving Cognitive
Health and Community History.
AB - Background and Objectives: Multimodal interventions are increasingly targeting
multiple cognitive decline risk factors. However, technology remains mostly
adjunctive, largely prioritizes age relevancy over cultural relevancy, and often
targets individual health without lasting, community-wide deliverables.
Meanwhile, African Americans remain overburdened by cognitive risk factors yet
underrepresented in cognitive health and technology studies. The Sharing History
through Active Reminiscence and Photo-imagery (SHARP) program increases physical,
social, and cognitive activity within a culturally meaningful context that
produces community deliverables-an oral history archive and cognitive health
education. Design and Methods: The SHARP application was tested with 19 African
Americans >=55 years, aiming for an easy, integrative, and culturally meaningful
experience. The application guided triads in walks 3 times weekly for 6 months in
Portland, Oregon's historically Black neighborhoods; local historical images
prompted recorded conversational reminiscence. Focus groups evaluated factors
influencing technology acceptance-attitudes about technology, usefulness,
usability, and relevance to integrating program goals. Thematic analysis guided
qualitative interpretation. Results: Technology acceptance was influenced by
group learning, paper-copy replicas for reluctant users, ease of navigation,
usefulness for integrating and engaging in health behaviors, relevance to
integrating individual benefit and the community priority of preserving history
amidst gentrification, and flexibility in how the community uses deliverables.
Perceived community benefits sustained acceptance despite intermittent technology
failure. Discussion and Implications: We offer applicable considerations for
brain health technology design, implementation, and deliverables that integrate
modalities, age, and cultural relevance, and individual and community benefit for
more meaningful, and thus more motivated community engagement.
PMID- 29961888
TI - Urinary [TIMP-2].[IGFBP7]-guided randomized controlled intervention trial to
prevent acute kidney injury in the emergency department.
AB - Background: Early detection and prevention of acute kidney injury (AKI) is
important to reduce morbidity and mortality. Discovery of early-detection
biomarkers has enabled early preventive approaches. There are no data on early
biomarker-guided intervention with nephrological consultation in emergency
departments (EDs). Methods: In this prospective randomized controlled
intervention trial, patients at high risk for AKI were screened with urinary
[TIMP-2].[IGFBP7] in the ED of Robert-Bosch-Hospital (Stuttgart, Germany). We
screened 257 eligible patients of whom 100 met the inclusion criteria, with
urinary [TIMP-2].[IGFBP7] >0.3, and were included. The intervention group
received immediate one-time nephrological consultation after randomization,
implementing Kidney Disease: Improving Global Outcomes (KDIGO) 2012
recommendations on AKI. The primary outcome was the incidence of moderate to
severe AKI within the first day after admission. Secondary outcomes were AKI
occurrence within 3 days after admission, need for renal replacement therapy
(RRT), length of hospital stay and death. Results: The primary outcome did not
differ significantly (P = 0.9) between the groups, neither within the first day
nor within the first 3 days after admission. The intervention group had
significantly (P < 0.05) lower serum creatinine (SCr) on Day 2 and lower maximum
SCr and tended (P = 0.08) to have higher urine output (UOP) at Day 3 than the non
intervention group. No patient in the intervention group needed RRT (0 versus 3)
during the hospital stay (P = 0.09). Conclusions: One-time routine nephrologist
guided application of the KDIGO bundle in ED patients with a risk for AKI cannot
currently be recommended. However, due to the uniform trend of study endpoints in
favour of intervention, further trials to investigate larger cohorts of more
severely ill patients are warranted. Trial registration: www.ClinicalTrials.gov,
study number NCT02730637.
PMID- 29961889
TI - Action of Neurotensin, CRH, and RFRP-3 in E2-induced Negative Feedback Control:
Studies Using a Mouse ARC Hypothalamic Cell Model.
AB - The recently established immortalized hypothalamic cell model mHypoA-55 possesses
characteristics similar to those of Kiss-1 neurons in the arcuate nucleus (ARC)
region of the hypothalamus. Here, we show that Kiss-1 gene expression in these
cells was downregulated by 17beta-estradiol (E2) under certain conditions. Both
neurotensin (NT) and corticotropin-releasing hormone (CRH) were expressed in
these cells and upregulated by E2. Stimulation of mHypoA-55 cells with NT and CRH
significantly decreased Kiss-1 mRNA expression. A mammalian gonadotropin
inhibitory hormone homolog, RFamide-related peptide-3 (RFRP-3), was also found to
be expressed in mHypoA-55 cells, and RFRP-3 expression in these cells was
increased by exogenous melatonin stimulation. E2 stimulation also upregulated
RFRP-3 expression in these cells. Stimulation of mHypoA-55 cells with RFRP-3
significantly increased the expression of NT and CRH. Furthermore, melatonin
stimulation resulted in the increase of both NT and CRH mRNA expression in mHypoA
55 cells. On the other hand, in experiments using mHypoA-50 cells, which were
originally derived from hypothalamic neurons in the anteroventral periventricular
nucleus, Kiss-1 gene expression was upregulated by both NT and CRH, although E2
increased both NT and CRH expression, similarly to the mHypoA-55 cells.Our
observations using the hypothalamic ARC cell model mHypoA-55 suggest that NT and
CRH have inhibitory effects on Kiss-1 gene expression under the influence of E2
in association with RFRP-3 expression. Thus, these neuropeptides might be
involved in E2-induced negative feedback mechanisms.
PMID- 29961890
TI - Viral Load in the Natural History of Human Papillomavirus Infection Among Men in
Rural China: A Population-based Prospective Study.
AB - Background: High-risk human papillomavirus (HR-HPV) load is predictive of HR-HPV
persistence and subsequent carcinogenesis in women. However, in men, data on
genital HPV load and its effect on the natural history of HPV infection are
limited. Methods: The subjects included 1532 men aged 25-65 years with up to 7
biannual visits for evaluation of genital HPV load in rural China during 2009
2013 who were positive for >=1 of the 18 selected HPV types (including 10 HR-HPV
types) detected by general primer-mediated polymerase chain reaction (PCR) and
sequencing. Type-specific HPV load was quantified with real-time PCR and
dichotomized based on median values. Results: Men with multiple lifetime sex
partners were more likely to have higher overall levels of HR-HPV load across
visits (adjusted odds ratio, 2.42; 95% confidence interval [CI], 1.12-5.24; 2
partners vs 0-1 partner). Higher levels of HR-HPV load at the time of the first
HPV diagnosis conferred an increased probability of the subject remaining type
specific HPV-positive up to 12 months and an increased probability of
persistent/intermittent infection (virus detected repeatedly with or without a
period of intercurrent negativity) versus transient infections (single-time
positive). Higher overall HR-HPV levels were predictive of reduced HR-HPV
clearance rates (adjusted hazard ratio, 0.47; 95% CI, .27-.83). Conclusions:
Having multiple lifetime sex partners is associated with increased male genital
HR-HPV load. Higher HR-HPV load predicts persistence of HR-HPV in men from rural
China.
PMID- 29961891
TI - Gene circuit engineering to improve the performance of a whole-cell lead
biosensor.
AB - To improve the performance of a whole-cell biosensor for lead detection, we
designed six gene circuits by re-configuring the regulatory elements and
incorporating positive feedback loops to the circuits. The lead resistance operon
pbr encodes six genes with pbrRT on one side of the promoter and pbrABCD on the
other side. PbrR, the divergent promoter it regulates, and GFP were used to
design the lead biosensors. One has pbrR and gfp on opposite sides of the
promoter mimicking the native operon. We re-configured it by placing pbrR and gfp
on the same side or under two separate promoters. The one with pbrR and gfp on
the same side demonstrated lead sensitivity 10 times higher than the others.
Positive feedback loop was introduced to these circuits. The strength of the
output signal from the designs with positive feedback loop was 1.5-2 times
stronger than those without positive feedback. This study demonstrates the
importance of configuration and positive feedback as effective strategies to
improve the performance of lead biosensors and they can be extended to the design
of other whole-cell biosensors.
PMID- 29961892
TI - Where is the human in the data? A guide to ethical data use.
AB - Being asked to write about the ethics of big data is a bit like being asked to
write about the ethics of life. Big data is now integral to so many aspects of
our daily lives-communication, social interaction, medicine, access to government
services, shopping, and navigation. Given this diversity, there is no one-size
fits-all framework for how to ethically manage your data. With that in mind, I
present seven ethical values for responsible data use.
PMID- 29961893
TI - Associations of Dietary Protein Intake With Fat-Free Mass and Grip Strength: A
Cross-Sectional Study in 146,816 UK Biobank Participants.
AB - Adequate dietary protein intake is important for the maintenance of fat-free mass
(FFM) and muscle strength, but optimal requirements remain unknown. Our aim in
the current study was to explore the associations of protein intake with FFM and
grip strength. We used baseline data from the UK Biobank (a study of 146,816
participants aged 40-69 years with data collected across the United Kingdom in
2007-2010) to examine the associations of protein intake with FFM and grip
strength. Protein intake was positively associated with FFM (men: 5.1% (95%
confidence interval (CI): 5.0, 5.2); women: 7.7% (95% CI: 7.7, 7.8)) and grip
strength (men: 0.076 kg/kg (95% CI: 0.074, 0.078); women: 0.074 kg/kg (95% CI:
0.073, 0.076)) per 0.5-g/kg/day (grams per kg of body mass per day) increment in
protein intake. FFM and grip strength were higher with higher intakes across the
full range of intakes (i.e., highest in persons who reported consuming >=2.00
g/kg/day) independently of sociodemographic factors, other dietary measures,
physical activity, and comorbidity. FFM and grip strength were lower with age,
but this association did not differ by category of protein intake (P > 0.05). The
current recommendation for all adults (ages 40-69 years) to maintain a protein
intake of 0.8 g/kg/day may need to be increased to optimize FFM and grip
strength.
PMID- 29961894
TI - Darwinian positive selection on the pleiotropic effects of KITLG explain skin
pigmentation and winter temperature adaptation in Eurasians.
AB - Human skin color diversity is considered an adaptation to environmental
conditions such as UV radiation. Investigations into the genetic bases of such
adaptation have identified a group of pigmentation genes contributing to skin
color diversity in African and non-African populations. Here we present a
population analysis of the pigmentation gene KITLG with previously reported
signal of Darwinian positive selection in both European and East Asian
populations. We demonstrated that there had been recurrent selective events in
the upstream and the downstream regions of KITLG in Eurasian populations. More
importantly, besides the expected selection on the KITLG variants favoring light
skin in coping with the weak UV radiation at high latitude, we observed a KITLG
variant showing adaptation to winter temperature. In particular, compared to UV
radiation, winter temperature showed a much stronger correlation with the
prevalence of the presumably adaptive KITLG allele in Asian populations. This
observation was further supported by the in vitro functional test at low
temperature. Consequently, the pleiotropic effects of KITLG, i.e. pigmentation
and thermogenesis were both targeted by natural selection that acted on different
KITLG sequence variants, contributing to the adaptation of Eurasians to both UV
radiation and winter temperature at high latitude areas.
PMID- 29961896
TI - Erratum to "Demographic Parameters of Lipaphis erysimi (Hemiptera: Aphididae) on
Different Cultivars of Brassica Vegetables".
PMID- 29961895
TI - Hookah Use among U.S. Youth: A Systematic Review of the Literature from 2009
2017.
AB - Introduction: Given the U.S. Food and Drug Administration (FDA)'s authority to
regulate hookah, more research is needed to inform regulations intended to
prevent youth from using hookah. This systematic review summarizes and assesses
the literature related to hookah use among adolescents (11 to <=18 years of age)
in the U.S. from 2009 to 2017. Methods: Database searches yielded 867 peer
reviewed articles. After duplicates were removed, authors reviewed 461 articles
for inclusion. Included articles (n=55) were coded for study themes, study
quality and their relevance to FDA's research priorities. A qualitative synthesis
is presented. Results: The following themes were identified: 1) prevalence of
hookah use (n=42); 2) tobacco use transitions (n=7); 3) sociodemographic
correlates (n=35); 4) psychosocial risk factors (n=21); 5) concurrent use of
other tobacco products (n=31); 6) concurrent use of other substances (n=9); and
7) other (n=15)-which includes low prevalence themes. The qualitative synthesis
showed increasing rates of hookah use. Older age, male gender, positive social
normative beliefs, higher peer use as well as lower perceived risk was associated
with hookah use. Longitudinal studies of youth hookah use showed bidirectional
relationships between use of hookah and other tobacco products. All articles fell
within FDA's research priority related to "behavior," and three priorities
("impact analysis," "health effects," and "toxicity") have not been explored for
hookah use among U.S. youth since 2009. Conclusions: The prevalence of hookah use
among youth in the U.S. is increasing, thus more research is needed to inform
policies targeted to protect this vulnerable population. Implications: This study
represents a novel contribution to our understanding of hookah use among youth in
the United States (U.S.) from 2009-the year that the Family Smoking Prevention
and Tobacco Control Act was passed-to 2017. In recent years, hookah has become a
more popular tobacco product among U.S. youth; however, to date, no systematic
reviews of hookah use among this population exist. Results highlight implications
for future U.S. Food and Drug Administration regulatory policy and identify gaps
in research to be addressed in future studies.
PMID- 29961898
TI - A new clinical staging system for esophageal cancer to predict survival after
definitive chemoradiation or radiotherapy.
AB - This study is to evaluate the prognostic value of a new clinical staging system
for esophageal cancer to predict survival after (chemo)radiotherapy. This
retrospective study enrolled 444 patients with esophageal squamous cell carcinoma
who underwent definitive intensity-modulated radiotherapy with or without
chemotherapy between January 2008 and May 2014. A clinical staging system based
on the gross tumor volume and maximum diameter of metastatic lymph nodes was
developed and the prognostic value of this staging system was compared with that
of the 8th edition of American Joint Committee on Cancer TNM staging system. The
3-year survival rate in the whole group was 44.5%. Multivariate analysis showed
that gross tumor volume and maximum diameter of metastatic lymph nodes were
independent prognostic factors. According to the proposed clinical staging
system, the 3-year survival curves of each T, N, and TNM stage were well
segregated. On the other hand, 3-year survival rates based on the 8th edition of
cTNM staging system were similar between cT3 and cT4, cN1 and cN2, cN2, and cN3,
III and IVa stages.The proposed clinical staging system appears to be a simple
and accurate predictor of outcome in patients with esophageal squamous cell
carcinoma who underwent definitive (chemo) intensity-modulated radiotherapy.
PMID- 29961897
TI - Targeting the PI3K/Akt/mTOR signaling pathway by pterostilbene attenuates mantle
cell lymphoma progression.
AB - Mantle cell lymphoma (MCL) is an aggressive and mostly incurable B-cell
malignancy with frequent relapses after an initial response to standard
chemotherapy. Therefore, novel therapies are urgently required to improve MCL
clinical outcomes. In this study, MCL cell lines were treated with pterostilbene
(PTE), a non-toxic natural phenolic compound primarily found in blueberries. The
antitumor activity of PTE was examined by using the Cell Counting Kit-8,
apoptosis assays, cell cycle analysis, JC-1 mitochondrial membrane potential
assay, western blot analysis, and tumor xenograft models. PTE treatment induced a
dose-dependent inhibition of cell proliferation, including the induction of cell
apoptosis and cell cycle arrest at the G0/G1 phase. Moreover, the PI3K/Akt/mTOR
pathway was downregulated after PTE treatment, which might account for the anti
MCL effects of PTE. Synergistic cytotoxicity was also observed, both in MCL cells
and in xenograft mouse models, when PTE was administered in combination with
bortezomib (BTZ). The antitumor effects of PTE shown in our study provide an
innovative option for MCL patients with poor responses to standardized therapy.
It is noteworthy that the treatment combining PTE with BTZ warrants clinical
investigation, which may offer an alternative and effective MCL treatment in the
future.
PMID- 29961899
TI - Models of cytokine dynamics in the inflammatory response of viral zoonotic
infectious diseases.
AB - Inflammatory responses to an infection from a zoonotic pathogen, such as avian
influenza viruses, hantaviruses and some coronaviruses, are distinctly different
in their natural reservoir versus human host. While not as well studied in the
natural reservoirs, the pro-inflammatory response and viral replication appear
controlled and show no obvious pathology. In contrast, infection in humans
results in an initial high viral load marked by an aggressive pro-inflammatory
response known as a cytokine storm. The key difference in the course of the
infection between the reservoir and human host is the inflammatory response. In
this investigation, we apply a simple two-component differential equation model
for pro-inflammatory and anti-inflammatory responses and a detailed mathematical
analysis to identify specific regions in parameter space for single stable
endemic equilibrium, bistability or periodic solutions. The extensions of the
deterministic model to two stochastic models account for variability in responses
seen at the cell (local) or tissue (global) levels. Numerical solutions of the
stochastic models exhibit outcomes that are typical of a chronic infection in the
natural reservoir or a cytokine storm in human infection. In the chronic
infection, occasional flare-ups between high and low responses occur when model
parameters are in a region of bistability or periodic solutions. The cytokine
storm with a vigorous pro-inflammatory response and less vigorous anti
inflammatory response occurs in the parameter region for a single stable endemic
equilibrium with a strong pro-inflammatory response. The results of the model
analyses and the simulations are interpreted in terms of the functional role of
the cytokines and the inflammatory responses seen in infection of the natural
reservoir or of the human host.
PMID- 29961901
TI - Efficient Preparation of Xylonic Acid from Xylonate Fermentation Broth by Bipolar
Membrane Electrodialysis.
AB - Preparation of xylonic acid from xylonate fermentation broth was studied in a
four-chamber bipolar membrane electrodialysis (BMED) setup. The effects of metal
ion size, current density, and xylonate concentration on BMED were evaluated
principally with respect to acid yield and partially with respect to efficiency
and energy consumption. Sodium xylonate was more successful than potassium
xylonate because of its smaller size and easier membrane penetrability for BMDE.
Efficient electrodialysis was achieved using 50 mA/cm2 current density for 14
min; thus, we obtained 92% xylonic acid from 100 g/L sodium xylonate fermentation
broth. In conclusion, BMED can be used for producing xylonic acid from
fermentation broth. Moreover, this study highlights ways of improving the
efficiency of BMED.
PMID- 29961902
TI - N-Acetyl-D-glucosamine Production by a Chitinase of Marine Fungal Origin: a Case
Study of Potential Industrial Significance for Valorization of Waste Chitins.
AB - Chitin is a linear homo-polymer of N-acetyl-D-glucosamine (GlcNAc) and the second
most abundant biopolymer after cellulose. Several industries rely on the
bioprocesses for waste chitin recycle and hydrolysis by chitinase (EC 3.2.1.14)
for potential healthcare applications through the production of its monomeric
subunit, GlcNAc. In the present study, a chitinase-producing fungus (named as
MFSRK-S42) was isolated from the marine water sample of North Bay of the Andaman
and Nicobar Islands. It was identified as Aspergillus terreus by morphological
and molecular characterization methods leveraging the internal transcribed spacer
between 18S rRNA and 5.8S rRNA. Chitinase that was isolated from the fermentation
broth of marine Aspergillus terreus was used to carry out biotransformation of
chitineaceous wastes. Prior to the enzymatic hydrolysis step, chitins from
different sources were characterized for the presence of characteristic
functional groups, grain size distribution, and surface morphology. Enzymatic
hydrolysis of 50 mg/ml substrate with six units of enzyme incubated for 5 days
revealed 15, 36.5, 40, and 46 mg/ml GlcNAc production from ground prawn shell,
chitin flakes, colloidal prawn shell, and swollen chitin respectively under
standardized conditions, as determined by HPLC. In this study, 30, 73, 80, and
92% GlcNAc yields were observed from ground prawn shell, chitin flakes, colloidal
prawn shell, and swollen chitin conversion respectively. The HPLC-eluted product
was confirmed as GlcNAc by the presence of characteristic functional groups in
FTIR and 244 Da molecular weight peak in HRMS analyses.
PMID- 29961903
TI - Acetic Acid Removal from Pre-Pulping Wood Extract with Recovery and Recycling of
Extraction Solvents.
AB - Pre-pulping extraction is a means of deriving a hemicellulose-rich process stream
from the front end of a kraft pulp mill. When the extraction is carried out using
green liquor, pulp quality and quantity can be retained while still releasing
hemicelluloses and acetic acid (HAc) for recovery as bioprocessing feedstock or
chemical products. The HAc that is present in the wood extraction is inhibitory
to microorganisms and can hinder fermentation. HAc is also a commodity chemical
that may provide sufficient value to justify recovery and purification. In this
study, a liquid-liquid extraction (LLE) method is applied to extract HAc from a
green liquor pre-pulping hardwood extract (GLE). The HAc removal is carried out
after acid hydrolysis and prior to fermentation. Two organic solutions:
trioctylphosphine oxide (TOPO) diluted in undecane and trioctylamine (TOA)
diluted in octanol were tested for their abilities to extract HAc from GLE and to
be recycled back through the process. GLE was contacted with the organic
solvents, phase separated by centrifugation, and the organic phase was then
distilled to recover the acetic acid. The solvent was then recycled back for a
subsequent extraction of fresh GLE. It was found that TOA was a superior
extractant, but failed to easily release its HAc through distillation. It also
quickly became contaminated with other compounds in the wood extracts and lost
its extraction efficiency after only a few recycles. The TOPO solvent did release
its HAc through distillation but also lost extraction capacity with recycling.
Back extraction of the TOPO solvent with sodium hydroxide solution restored the
performance of the TOPO solvent.
PMID- 29961904
TI - Next-generation sequencing identified a novel SPTB frameshift insertion causing
hereditary spherocytosis in China.
PMID- 29961900
TI - Cancer; an induced disease of twentieth century! Induction of tolerance,
increased entropy and 'Dark Energy': loss of biorhythms (Anabolism v.
Catabolism).
AB - Maintenance of health involves a synchronized network of catabolic and anabolic
signals among organs/tissues/cells that requires differential bioenergetics from
mitochondria and glycolysis (biological laws or biorhythms). We defined
biological circadian rhythms as Yin (tumoricidal) and Yang (tumorigenic) arms of
acute inflammation (effective immunity) involving immune and non-immune systems.
Role of pathogens in altering immunity and inducing diseases and cancer has been
documented for over a century. However, in 1955s decision makers in
cancer/medical establishment allowed public (current baby boomers) to consume
million doses of virus-contaminated polio vaccines. The risk of cancer incidence
and mortality sharply rose from 5% (rate of hereditary/genetic or innate disease)
in 1900s, to its current scary status of 33% or 50% among women and men,
respectively. Despite better hygiene, modern detection technologies and discovery
of antibiotics, baby boomers and subsequent 2-3 generations are sicker than
previous generations at same age. American health status ranks last among other
developed nations while America invests highest amount of resources for
healthcare. In this perspective we present evidence that cancer is an induced
disease of twentieth century, facilitated by a great deception of cancer/medical
establishment for huge corporate profits. Unlike popularized opinions that cancer
is 100, 200 or 1000 diseases, we demonstrate that cancer is only one disease; the
severe disturbances in biorhythms (differential bioenergetics) or loss of balance
in Yin and Yang of effective immunity. Cancer projects that are promoted and
funded by decision makers are reductionist approaches, wrong and unethical and
resulted in loss of millions of precious lives and financial toxicity to society.
Public vaccination with pathogen-specific vaccines (e.g., flu, hepatitis, HPV,
meningitis, measles) weakens, not promotes, immunity. Results of irresponsible
projects on cancer sciences or vaccines are increased population of drug
dependent sick society. Outcome failure rates of claimed 'targeted' drugs,
'precision' or 'personalized' medicine are 90% (+/- 5) for solid tumors. We
demonstrate that aging, frequent exposures to environmental hazards, infections
and pathogen-specific vaccines and ingredients are 'antigen overload' for immune
system, skewing the Yin and Yang response profiles and leading to induction of
'mild', 'moderate' or 'severe' immune disorders. Induction of decoy or pattern
recognition receptors (e.g., PRRs), such as IRAK-M or IL-1dRs ('designer'
molecules) and associated genomic instability and over-expression of growth
promoting factors (e.g., pyruvate kinases, mTOR and PI3Ks, histamine, PGE2, VEGF)
could lead to immune tolerance, facilitating cancer cells to hijack anabolic
machinery of immunity (Yang) for their increased growth requirements. Expression
of constituent embryonic factors would negatively regulate differentiation of
tumor cells through epithelial-mesenchymal-transition and create "dual negative
feedback loop" that influence tissue metabolism under hypoxic conditions. It is
further hypothesized that induction of tolerance creates 'dark energy' and
increased entropy and temperature in cancer microenvironment allowing disorderly
cancer proliferation and mitosis along with increased glucose metabolism via
Crabtree and Pasteur Effects, under mitophagy and ribophagy, conditions that are
toxic to host survival. Effective translational medicine into treatment requires
systematic and logical studies of complex interactions of tumor cells with host
environment that dictate clinical outcomes. Promoting effective immunity
(biological circadian rhythms) are fundamental steps in correcting host
differential bioenergetics and controlling cancer growth, preventing or delaying
onset of diseases and maintaining public health. The author urges independent
professionals and policy makers to take a closer look at cancer dilemma and stop
the 'scientific/medical ponzi schemes' of a powerful group that control a drug
dependent sick society before all hopes for promoting public health evaporate.
PMID- 29961905
TI - Phytoremediation of Mn-contaminated paddy soil by two hyperaccumulators
(Phytolacca americana and Polygonum hydropiper) aided with citric acid.
AB - The purpose of this study was to investigate the phytoremediation potential of
two hyperaccumulator plants, Phytolacca americana L. and Polygonum hydropiper L.,
on manganese-contaminated paddy soils. The biomass growth, Mn concentrations in
plant tissues, and potential Mn removal efficiency from soils of these two plants
were studied with citric acid, and the mechanisms of citric acid on these two
plants were analyzed by examining the root activity, the activities of superoxide
dismutase (SOD), peroxidase (POD) and catalase (CAT) in leaves, as well as the
concentrations of O2.- and H2O2 in leaves. The results showed that the biomass of
these two plants were both promoted under low level of citric acid (3 mmol kg-1).
The concentration of Mn in the plants and the amount of Mn removed from the soil
by the plants through harvesting were enhanced at low and intermediate (10 mmol
kg-1) citric acid application levels. The results also showed that root activity
was enhanced at the low citric acid level and significantly inhibited under the
intermediate and high levels (15 mmol kg-1), which indicates the facilitative
function of the low level of citric acid and the inhibitive function of the high
level of citric acid application on plant biomass growth. Under the low and
intermediate levels of citric acid application, O2.- in the plant leaves
increased sharply, and the SOD, POD, and CAT activities also increased sharply,
which made the level of H2O2 very similar to that of the control, ensuring the
health of the plants. At the high level of citric acid application, however, the
O2.- continued to rise sharply, while the activity of the three antioxidant
enzymes declined sharply, causing the concentration of hydrogen peroxide to be
much higher than that in the control, thus endangering the plants. The present
study shows the potential of P. hydropiper for use in the phytoremediation of
soil contaminated with a relatively low level of manganese.
PMID- 29961906
TI - Modelling local uncertainty in relations between birth weight and air quality
within an urban area: combining geographically weighted regression with
geostatistical simulation.
AB - In this study, we combine known methods to present a new approach to assess local
distributions of estimated parameters measuring associations between air quality
and birth weight in the urban area of Sines (Portugal). To model exposure and
capture short-distance variations in air quality, we use a Regression Kriging
estimator combining air quality point data with land use auxiliary data. To
assess uncertainty of exposure, the Kriging estimator is incorporated in a
sequential Gaussian simulation algorithm (sGs) providing a set of simulated
exposure maps with similar spatial structural dependence and statistical
properties of observed data. Following the completion of the simulation runs, we
fit a geographically weighted generalized linear model (GWGLM) for each mother's
place of residence, using observed health data and simulated exposure data, and
repeat this procedure for each simulated map. Once the fit of GWGLM with all
exposure maps is finished, we take the distribution of local estimated parameters
measuring associations between exposure and birth weight, thus providing a
measure of uncertainty in the local estimates. Results reveal that the
distribution of local parameters did not vary substantially. Combining both
methods (GWGLM and sGs), however, we are able to incorporate local uncertainty on
the estimated associations providing an additional tool for analysis of the
impacts of place in health.
PMID- 29961907
TI - Impact of PM10 and meteorological factors on the incidence of hand, foot, and
mouth disease in female children in Ningbo, China: a spatiotemporal and time
series study.
AB - Hand, foot, and mouth disease (HFMD) is a viral illness that is considered a
critical public health challenge worldwide. Previous studies have demonstrated
that meteorological parameters are significantly related to the incidence of HFMD
in children; however, few studies have focused only on female children. This
study quantified the associations of HFMD incidence with meteorological
parameters and PM10 (particulate matter with an aerodynamic diameter of 10 MUm)
among female children. Data were collected on daily HFMD cases, meteorological
variables, and PM10 levels in Ningbo, China, from January 2012 to December 2016.
Data were assessed using a distributed lag nonlinear model (DLNM) with Poisson
distribution. A total of 59,809 female children aged 0-15 years with HFMD were
enrolled. The results showed that highest relative risk (RR) of HFMD for
temperature was 3 degrees C and the lag effect was 3 days. The highest RR for
PM10 was 80 mg/m3 and the lag effect was 5 days. Spatial analysis showed that
female HFMD incidence was mainly concentrated in the suburban of Ningbo city
indicating that female children in this area should be more paid attention on
avoiding this disease outbreak. Our findings suggest that HFMD prevention
strategies should focus more attention on local meteorological parameters.
PMID- 29961908
TI - Differences of Cd uptake and expression of MT family genes and NRAMP2 in two
varieties of ryegrasses.
AB - In order to understand the mechanism of the difference of Cd absorption and Cd
enrichment in different ryegrass varieties, pot experiment was conducted to study
on the response of two varieties of ryegrass (Bond and Abbott) to Cd stress as
well as the differences of Cd uptake and expression of MT family genes and
NRAMP2. Results showed that root dry weights of two varieties and shoot dry
weights of Abbott increased first and then decreased with the increase of Cd
level in soil. When exposed to 75 mg kg-1 Cd, shoot dry weight and plant dry
weight of Abbott both reached maximum values (10.92 and 12.03 g pot-1), which
increased by 11.09 and 10.67% compared with the control, respectively. Shoot dry
weight and plant dry weight of Bond decreased with the increase of Cd level in
soil. When the Cd level in soil was 75 mg kg-1, shoot Cd concentrations of the
two varieties were 111.19 mg kg-1 (Bond) and 133.69 mg kg-1 (Abbott),
respectively, both of which exceeded the critical value of Cd hyperaccumulator
(100 mg kg-1). The expression of MT gene family and NRAMP2 in the leaf of Bond
variety significantly increased at the Cd level of 75 mg kg-1 and reached maximum
value (except MT2C) at Cd level of 150 mg kg-1. The expression of MT gene family
in the stem of Bond variety showed a double-peak pattern, while the expression of
NRAMP2 was a single-peak pattern. The expression of MT gene family and NRAMP2 in
Abbott variety was consistent with single-peak pattern. The expression of MT gene
family and NRAMP2 in leaf both significantly increased at Cd level of 150 mg kg
1, while that in stem and root significantly increased at Cd level of 75 mg kg-1.
For both varieties of ryegrass, the expression amount of MT family genes and
Nramp2 in leaf was higher than that in root and stem, indicating the Cd tolerance
of ryegrass can be improved by increasing the expression levels of MT family
genes and Nramp2 in stem and root. There was significant genotypic difference in
the expression of MT gene family and NRAMP2 between the two varieties of
ryegrass, and the expression of MT gene family and NRAMP2 in leaves and stems of
Bond variety was higher than that in Abbott variety, while the expression of MT
gene family and NRAMP2 in roots of Abbott variety was higher than that in Bond
variety. The two gene families investigated in this study may be closely related
to Cd uptake, but not related to Cd transport from root to leaf and Cd enrichment
in shoot.
PMID- 29961910
TI - Traumatic posterior atlantoaxial dislocation with associated C1 Jefferson
fracture and bilateral vertebral artery occlusion without odontoid process
fracture or neurological deficit.
AB - PURPOSE: Traumatic atlantoaxial dislocation (AAD) is usually associated with
fatal high-velocity road traffic accidents (Xu et al. in Medicine (Baltimore)
94:e1768, 2015). There are few reports of survival following posterior AAD
without odontoid fracture (Xu et al. 2015; Zhen et al. in Arch Orthop Trauma Surg
131:681-685, 2011; de Carvalho and Swash in Handb Clin Neurol 119:435-448, 2014).
METHOD: We present a previously undescribed case of posterior AAD associated with
a C1 Jefferson fracture but no odontoid fracture and bilateral vertebral artery
occlusion without neurological deficit. CONCLUSION: The presence of bilateral
vertebral artery occlusion raised challenges in the surgical management. Survival
was only possible due to the presence of robust cerebral collateral circulation.
PMID- 29961912
TI - Winning images from the Photography in Medical Physics (PiMP) competition.
PMID- 29961913
TI - Medical physics workforce modelling: do we need what we want?
PMID- 29961911
TI - Gastric Antral Vascular Ectasia Pathogenesis and the Link to the Metabolic
Syndrome.
AB - PURPOSE OF REVIEW: Gastric antral vascular ectasia (GAVE) is a well-described
source of chronic blood loss. We aim to review the previously hypothesized
etiologies of GAVE and focus on recent proposed mechanisms, including metabolic
syndrome. We will support these theories with newly discovered clinical
associations and possible therapeutic implications. RECENT FINDINGS:
Historically, GAVE has been associated with connective tissue disease and liver
disease. Based on these associations and its histologic appearance, GAVE has
presumed to be caused by mechanical- and hormonally mediated injury. Recent
findings have been notable for a clinical association with aspects of the
metabolic syndrome. Therefore, the pathogenic etiology may be akin to aspects of
the metabolic syndrome via microvascular injury and neoangiogenesis. The
potential etiologies of GAVE include hypergastrinemia, mechanical injury, and
microvascular injury with neovascular proliferation particularly in the metabolic
syndrome. Further research is needed to evaluate these proposed mechanisms and
potential targets for treatment.
PMID- 29961915
TI - Ending the Opioid Epidemic by Changing the Culture.
AB - The opioid epidemic continues to take thousands of lives each year in the United
States, more than motor vehicle accidents and suicides combined. Real solutions,
based on science, will require a culture shift in the way that we think about and
respond to substance use disorders, in the healthcare system and in our
communities. Just more of the same approach will not turn the tide. This article
discusses how to better understand the use of psychoactive drugs and how
prevention, treatment and policy change can disseminate evidence-based practices,
fight stigma, and advance harm reduction; not only as strategies to improve
outcomes, but as a social justice movement as well.
PMID- 29961914
TI - Comparative study of microRNA profiling in one Chinese Family with PSEN1 G378E
mutation.
AB - MicroRNAs are not widely studied in familial Alzheimer's disease cases, whether
the microRNA profilings in familial Alzheimer's disease patients are similar to
the sporadic AD patients is not known. This study aims to investigate the
differential expression of microRNAs (miRNAs) associated with early-onset
familial Alzheimer's disease (EO-FAD) in a Chinese family. We performed the gene
mutation analysis in a family clinically diagnosed of EO-FAD. Micro-arrays were
used to profile the miRNAs in cerebrospinal fluid of 2 affected members, 2
unaffected carriers and 2 mutation negative controls. The clinical presentation
confirmed the EO-FAD diagnosis, and a recurrent mutation of the PSEN1 p.G378E was
found in the family. The result showed that in the miRNAs expression profile, a
total of 166 miRNAs were up-regulated and 3 miRNAs were down-regulated in the
affected individuals compared with mutation negative individuals. But after
Benjamini Hochberg FDR correction, only 25 miRNAs were significantly up-regulated
and no miRNA was down-regulated, the levels of miR-30a-5p, miR-4758-3p and let-7a
3p were elevated significantly. Compared with mutation negative controls, 21
miRNAs were up-regulated and 18 microRNAs were down-regulated in the unaffected
mutation carriers, after Benjamini Hochberg FDR correction, miR-345-5p was up
regulated and miR-4795-3p was down-regulated in the unaffected mutation carriers.
And there was no difference between the affected members and unaffected mutation
carriers. GO database showed that the top biological processes affected by the
predicted target genes are nucleic acid binding transcription factor activity and
transcription factor activity (sequence-specific DNA binding) (GO:0001071 and
GO:0003700). The result of KEGG pathways showed 64 pathways were implicated in
the regulatory network. The present study identified the miRNA profiling of
Chinese siblings with G378E mutation in the PSEN1. Compared with mutation
negative controls, the levels of 25 miRNAs including miR-30a-5p, miR-4758-3p and
let-7a-3p were elevated significantly in the affected members, miR-345-5p was up
regulated and miR-4795-3p was down-regulated in the unaffected mutation carriers.
Our study showed the microRNA profilings in the cases of a EO-FAD family with
PSEN1 p.G378E mutation, but because of the individuals in the family was small,
the results in other types of EO-FAD still need further studied.
PMID- 29961916
TI - Gastropods and Insects Prefer Different Solanum dulcamara Chemotypes.
AB - Solanum dulcamara (Bittersweet nightshade) shows significant intraspecific
variation in glycoalkaloid (GA) composition and concentration. We previously
showed that constitutive differences in overall GA levels are correlated with
feeding preference of the grey field slug (GFS; Deroceras reticulatum). One
particularly preferred accession, ZD11, contained low GA levels, but high levels
of previously unknown structurally related uronic acid conjugated compounds
(UACs). Here we test whether different slug species as well as insect herbivores
show similar feeding preferences among six S. dulcamara accessions with different
GA chemotypes. In addition, we investigate whether slug feeding can lead to
induced changes in the chemical composition and affect later arriving herbivores.
A leaf disc assay using greenhouse-grown plants showed that three slug species
similarly preferred accessions with low GA levels. Untargeted metabolomic
analyses showed that previous slug feeding consistently increased the levels of N
caffeoyl-putrescine and a structurally related metabolite, but not the levels of
GAs and UACs. Slug-induced responses only affected slug preference in one
accession. A common garden experiment using the same six accessions revealed that
ZD11 received the highest natural gastropod feeding damage, but suffered the
lowest damage by specialist flea beetles. The latter preferred to feed on
accessions with high GA levels. Our study indicates that different selection
pressures imposed by generalist gastropods and specialist insects may explain
part of the observed chemical diversity in S. dulcamara.
PMID- 29961919
TI - Pazopanib Monotherapy Is Active in Relapsed and Refractory Metastatic
Gastroesophageal Adenocarcinoma and Can Produce Durable Response.
PMID- 29961917
TI - Molecular basis of atypicality of bupropion inferred from its receptor engagement
in nervous system tissues.
AB - Despite decades of clinical use and research, the mechanism of action (MOA) of
antidepressant medications remains poorly understood. Selective serotonin
reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors
(SNRIs) are the most commonly prescribed antidepressants-atypical antidepressants
such as bupropion have also proven effective, while exhibiting a divergent
clinical phenotype. The difference in phenotypic profiles presumably lies in the
differences among the MOAs of SSRIs/SNRIs and bupropion. We integrated the
ensemble of bupropion's affinities for all its receptors with the expression
levels of those targets in nervous system tissues. This "combined target tissue"
profile of bupropion was compared to those of duloxetine, fluoxetine, and
venlafaxine to isolate the unique target tissue effects of bupropion. Our results
suggest that the three monoamines-serotonin, norepinephrine, and dopamine-all
contribute to the common antidepressant effects of SSRIs, SNRIs, and bupropion.
At the same time, bupropion is unique in its action on 5-HT3AR in the dorsal root
ganglion and nicotinic acetylcholine receptors in the pineal gland. These unique
tissue-specific activities may explain unique therapeutic effects of bupropion,
such as pain management and smoking cessation, and, given melatonin's association
with nicotinic acetylcholine receptors and depression, highlight the
underappreciated role of the melatonergic system in bupropion's MOA.
PMID- 29961918
TI - Risk of secondary rectal cancer and colon cancer after radiotherapy for prostate
cancer: a meta-analysis.
AB - PURPOSE: To investigate whether radiotherapy for prostate cancer increases the
risk of therapy-related rectal cancer and colon cancer. METHODS: A systematic
literature search was carried out using the Medline (PubMed), EMBASE, and the
Cochrane Library to identify studies examining the association between
radiotherapy for prostate cancer and secondary colorectal cancer (rectal cancer
and colon cancer) published before March 19, 2018. The risk of second colorectal
cancer after radiotherapy was summarized using unadjusted odds ratio (OR) and
adjusted hazard ratio (HR) with their 95% confidence interval (CI). Subgroup and
sensitivity analyses were conducted to detect potential bias and heterogeneity.
RESULTS: After study selection, 16 reports were retrieved for analysis. When
patients received radiotherapy compared with those unexposed to radiation, there
was an increased risk of the rectal cancer (OR 1.37, 95%CI 1.01 to 1.85), but not
colon cancer. According to adjusted HR, there was an increased risk of the rectal
cancer (HR 1.64, 95%CI 1.39 to 1.94), and colon cancer (HR 1.33, 95%CI 1.02 to
1.76). The OR for rectal cancer showed an increased risk with longer latent
period (5 years lag time versus 10 years lag time, OR: 1.56 versus 2.22).
Brachytherapy had no association with second cancer across all analyses.
CONCLUSIONS: Radiotherapy was associated with an increased risk of subsequent
rectal cancer compared with patients unexposed to radiation. Colon may be free
from the damage of radiation. Brachytherapy had no association with second rectal
cancer or colon cancer.
PMID- 29961920
TI - Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men.
AB - Fibroblast growth factor 23 (FGF23) is a major endocrine regulator of phosphate
and 1,25 (OH)2 vitamin D3 metabolism and is mainly produced by osteocytes. Its
production is upregulated by a variety of factors including 1,25 (OH)2 vitamin
D3, high dietary phosphate intake, and parathyroid hormone (PTH). Recently, iron
deficiency and hypoxia have been suggested as additional regulators of FGF23 and
a role of erythropoietin (EPO) was shown. However, the regulation of FGF23 by EPO
and the impact on phosphate and 1,25(OH)2 vitamin D3 are not completely
understood. Here, we demonstrate that acute administration of recombinant human
EPO (rhEPO) to healthy humans increases the C-terminal fragment of FGF23 (C
terminal FGF23) but not intact FGF23 (iFGF23). In mice, rhEPO stimulates acutely
(24 h) C-terminal FGF23 but iFGF23 only after 4 days without effects on PTH and
plasma phosphate. 1,25 (OH)2 D3 levels and alphaklotho expression in the kidney
decrease after 4 days. rhEPO induced FGF23 mRNA in bone marrow but not in bone,
with increased staining of FGF23 in CD71+ erythroid precursors in bone marrow.
Chronic elevation of EPO in transgenic mice increases iFGF23. Finally, acute
injections of recombinant FGF23 reduced renal EPO mRNA expression. Our data
demonstrate stimulation of FGF23 levels in mice which impacts mostly on 1,25
(OH)2 vitamin D3 levels and metabolism. In humans, EPO is mostly associated with
the C-terminal fragment of FGF23; in mice, EPO has a time-dependent effect on
both FGF23 forms. EPO and FGF23 may form a feedback loop controlling and linking
erythropoiesis and mineral metabolism.
PMID- 29961921
TI - Flattening of retinal pigment epithelial detachments after pneumatic displacement
of submacular hemorrhages secondary to age-related macular degeneration.
AB - PURPOSE: Pneumatic displacement of submacular hemorrhages (SMHs) with
intravitreal injection of sulfur hexafluoride (SF6) gas with or without tissue
plasminogen activator (tPA) and prone posturing is an effective minimally
invasive treatment. We observed some cases in which simultaneous flattening of
hemorrhagic pigment epithelial detachments (PEDs) occurred after prone posturing.
This study evaluated the impact of pneumatic displacement using tPA to treat PEDs
and visual outcomes in eyes with SMHs secondary to neovascular age-related
macular degeneration (AMD). METHODS: This retrospective analysis reviewed the
medical records of 32 patients (33 eyes) who underwent pneumatic displacement for
AMD-associated SMHs. The SMHs were related to polypoidal choroidal vasculopathy
(PCV) in 24 eyes and typical AMD in nine eyes and treated with intravitreal
injection of SF6 gas with tPA. We assessed the postoperative best-corrected
visual acuities (BCVAs), prevalence and flattening rates of the PEDs, and the
number of additional treatments. RESULTS: The mean follow-up period was 35.4 +/-
19.8 months. The BCVAs improved significantly in eyes with PCV compared with eyes
with typical AMD. Thirty-one (93.9%) of 33 eyes had an accompanying PED. The PEDs
flattened in 14 (58.3%) of 24 eyes with PCV but in only one (14.3%) of seven eyes
with typical AMD (p = 0.04). A mean of one additional treatment was administered
during the first year in 15 eyes with flattened PEDs, which was significantly (p
< 0.05) fewer than the 3.6 additional treatments in 16 eyes with persistent PEDs.
CONCLUSIONS: PEDs often accompany SMHs secondary to neovascular AMD. Pneumatic
displacement of the SMHs using tPA unexpectedly flattened the PEDs, especially in
eyes with PCV, and was associated with fewer additional treatments.
PMID- 29961922
TI - Association between polymorphisms in genes encoding estrogen receptors (ESR1 and
ESR2) and excreted bisphenol A levels after orthodontic bracket bonding: a
preliminary study.
AB - BACKGROUND: Bisphenol A (BPA) is released from orthodontic composites used for
bracket bonding. Genetic variations could modify the metabolism of this chemical
within the organism. Considering that free BPA binds to estrogen receptors
causing harmful effects to health, the present in vivo study aimed to evaluate
the association between genetic polymorphisms in genes encoding estrogen
receptors (ESR1 and ESR2) and excreted BPA levels in orthodontic patients.
METHODS: Quantification of BPA levels in the urine of 16 patients was performed
in a gas chromatograph mass spectrometer before (T0), at 24 h (T1), and 1 week
(T2) after bracket bonding. DNA was extracted from saliva, and one genetic
polymorphism in ESR1 (rs2234693) and two in ESR2 (rs4986938 and rs1256049) were
analyzed by real-time PCR. Increases in BPA levels in the urine at T1 and T2 were
grouped according to the genotype, and mean differences were compared by unpaired
T test or Mann-Whitney test according to the normality of the data. The
established alpha was 5%. RESULTS: BPA levels increased significantly at T1 and
T2. There were no statistically significant differences in the increases in BPA
levels according to the genotype for any genetic polymorphism (P > 0.05), at
neither 24 h nor 1 week after bracket bonding. CONCLUSIONS: The results suggested
that there are no association between excreted BPA levels after bracket bonding
and the evaluated genetic polymorphisms in ESR1 and ESR2. Further research should
be performed in order to confirm these results.
PMID- 29961923
TI - Wood anatomical traits highlight complex temperature influence on Pinus cembra at
high elevation in the Eastern Alps.
AB - Climate sensitivity of populations at the margins of their distribution range is
of key importance to understand species' responses to future warming conditions.
Pinus cembra is of particular interest being a typical high-elevation taxon,
spread with mostly scattered populations within its actual range, but still
overlooked in traditional dendrochronological researches due to low tree-ring
variability and climate sensitivity. With a different approach, we analyzed time
series of xylem anatomical traits, split into intra-ring sectors, and used daily
climate records over 89 years (1926-2014) aiming to improve the quality and time
resolution of the climate/growth associations. From nine trees growing at their
altitudinal limit and on 1.5 * 106 tracheids, we measured ring width (MRW), cell
number per ring, lumen area (LA), and cell-wall thickness (CWT). We then computed
correlations with monthly and fortnightly climate data. Late-spring and summer
temperature emerged as the most important factors. LA and especially CWT showed a
stronger temperature response than MRW, starting in mid-May and early June,
respectively. CWT also evidenced the longest period of correlations with
temperature and a significant difference between latewood radial and tangential
walls. Analysis of xylem anatomical traits at intra-ring level and the use of
daily temperature records proved to be useful for high resolution and detailed
climate/growth association inferences in Pinus cembra.
PMID- 29961924
TI - Histogram analysis of apparent diffusion coefficient maps for differentiating
malignant from benign parotid gland tumors.
AB - PURPOSE: To evaluate the diagnostic performance of histogram parameters derived
from diffusion-weighted imaging (DWI) for differentiating malignant from benign
parotid gland tumors compared with that of hotspot region of interest (ROI)-based
apparent diffusion coefficient (ADC) measurement. METHODS: Our study
retrospectively enrolled 60 patients with parotid gland tumors who had undergone
DWI scan for pre-treatment evaluation. ADC measurements were performed using
hotspot ROI (ADCHS-ROI)-based and histogram-based approach. Histogram parameters
included mean (ADCmean), median (ADCmedian), 10th (ADC10), 90th (ADC90)
percentiles, skewness and kurtosis of ADC. Mann-Whitney U test, Kruskal-Wallis
test with post hoc Dunn-Bonferroni method and receiver operating characteristic
(ROC) curve analyses were used for statistical analyses. RESULTS: ADCHS-ROI and
ADC histogram parameters showed no significant differences between malignant and
benign parotid gland tumors (All Ps > 0.05). Within the sub-group analyses,
Warthin's tumors showed the lowest ADCHS-ROI, ADCmean, ADCmedian, ADC10 and ADC90
value, followed by malignant tumors and pleomorphic adenomas (All Ps < 0.05).
ADC10 out-performed ADCHS-ROI in differentiating malignant tumors from
pleomorphic adenomas (area under curve, 0.890 vs 0.821; sensitivity, 79.31 vs
82.76%; specificity, 90.91 vs 72.73%; P = 0.016), and improved the diagnostic
performance in differentiating malignant tumors from Warthin's tumors (area under
curve, 1.000 vs 0.965; sensitivity, 100.00 vs 90.91%), although the difference
was not significant (P = 0.348). CONCLUSIONS: ADC histogram analysis, especially
ADC10, might be a promising imaging biomarker for characterizing parotid gland
tumors.
PMID- 29961925
TI - Workers compensation-reported injuries among security and law enforcement
personnel in the private versus public sectors.
AB - BACKGROUND: Private and Public security and law enforcement (SLE) sectors perform
multiple overlapping job duties. METHODS: Workers' compensation (WC) SLE first
reports of injury (FROI) data (2005-2015) were analyzed to describe injuries,
identify differences in awarded WC benefits, and compare the probability of a
FROI resulting in awarded benefits between Public and Private SLE. A Pearson's
chi-square test was utilized and reverse selection logistic regression was
performed to estimate the odds ratio that a FROI would result in an awarded
benefit for Private vs. Public SLE, while adjusting for relevant covariates.
RESULTS: Private SLE had higher FROI percentages for younger and for older
workers, fall injuries, and back injuries, compared to Public SLE. The adjusted
odds that a FROI resulted in an awarded benefit was 1.4 times higher for Private
SLE compared to Public SLE; (95% confidence interval [CI] = 1.09,1.69). Middle
aged SLE employee adjusted odds of awarded benefits was 3.3 times (95% CI [1.96,
5.39]) higher compared to younger employees. Adjusted odds of awarded benefits
was 3.8 times (95% CI [1.34, 10.61]) higher for gunshots and 1.7 times (95% CI
[1.22, 2.39]) higher for fractures/dislocations compared to other nature of
injuries. Motor vehicle injury, fall/slip, and strain related FROIs had elevated
adjusted odds of awarded benefits compared to other injury causes. CONCLUSIONS:
Results highlight the importance of injury prevention education and worker safety
training for Private and Public SLE sector workers on fall prevention (especially
in Private SLE) and strain prevention (especially in Public SLE), as well as
motor vehicle safety.
PMID- 29961926
TI - De-escalation of Therapy in Inflammatory Bowel Disease.
AB - PURPOSE OF REVIEW: Currently, inflammatory bowel disease treatment is based on
immunomodulators (IM) and/or biologic as this strategy may prevent the
development of irreversible damage. Nevertheless, long-term treatment may be
associated with non-negligible side effects and with high costs, and therefore
the question on whether therapy can be de-escalated is often posed in clinical
practice. RECENT FINDINGS: Recent studies have shown a predictable rate of
relapse after stop biologic or IM therapy withdrawal. Overall, around 40-50% of
patients will eventually relapse over the following year after drug withdrawal,
and the rates will increase over time. Stratification of patients and therapeutic
drug monitoring could be promising alternatives to guide therapeutic management.
We reviewed the current evidence on de-escalation strategy and summarised the
recent results on discontinuation and dose reduction. Nowadays, de-escalation
strategy is still a case-by-case decision in highly selected patients.
PMID- 29961927
TI - Building Schools' Readiness to Implement a Comprehensive Approach to School
Safety.
AB - Research consistently finds that a comprehensive approach to school safety, which
integrates the best scientific evidence and solid implementation strategies,
offers the greatest potential for preventing youth violence and promoting mental
and behavioral health. However, schools and communities encounter enormous
challenges in articulating, synthesizing, and implementing all the complex
aspects of a comprehensive approach to school safety. This paper aims to bridge
the gap between scientific evidence and the application of that evidence in
schools and communities by defining the key components of a comprehensive
approach to school safety and describing how schools can assess their readiness
to implement a comprehensive approach. We use readiness and implementation data
from the Safe Communities Safe Schools project to illustrate these challenges and
solutions. Our findings suggest that (1) readiness assessment can be combined
with feasibility meetings to inform school selection for implementation of a
comprehensive approach to school safety and (2) intentionally addressing
readiness barriers as part of a comprehensive approach may lead to improvements
in readiness (motivation and capacity) to effectively implement a comprehensive
approach to school safety.
PMID- 29961928
TI - New insights into the role of HNF-1beta in kidney (patho)physiology.
AB - Hepatocyte nuclear factor-1beta (HNF-1beta) is an essential transcription factor
that regulates the development and function of epithelia in the kidney, liver,
pancreas, and genitourinary tract. Humans who carry HNF1B mutations develop
heterogeneous renal abnormalities, including multicystic dysplastic kidneys,
glomerulocystic kidney disease, renal agenesis, renal hypoplasia, and renal
interstitial fibrosis. In the embryonic kidney, HNF-1beta is required for
ureteric bud branching, initiation of nephrogenesis, and nephron segmentation.
Ablation of mouse Hnf1b in nephron progenitors causes defective tubulogenesis,
whereas later inactivation in elongating tubules leads to cyst formation due to
downregulation of cystic disease genes, including Umod, Pkhd1, and Pkd2. In the
adult kidney, HNF-1beta controls the expression of genes required for intrarenal
metabolism and solute transport by tubular epithelial cells. Tubular
abnormalities observed in HNF-1beta nephropathy include hyperuricemia with or
without gout, hypokalemia, hypomagnesemia, and polyuria. Recent studies have
identified novel post-transcriptional and post-translational regulatory
mechanisms that control HNF-1beta expression and activity, including the miRNA
cluster miR17 ~ 92 and the interacting proteins PCBD1 and zyxin. Further
understanding of the molecular mechanisms upstream and downstream of HNF-1beta
may lead to the development of new therapeutic approaches in cystic kidney
disease and other HNF1B-related renal diseases.
PMID- 29961929
TI - Why does invasion imply substitution? Beyond the paradigm of invasion fitness.
AB - Adaptive dynamics combines deterministic population dynamics of groups having
different trait values and random process describing mutation and tries to
predict the course of evolution of a species of interest. One of basic interests
is to know which group survives, residents or mutants. By using invasion fitness
as the primary tool, "invasion implies substitution" principle, IIS principle for
short, has been established under the existence of a generating function in the
sense of Brown and Vincent (Theor Popul Biol 31(1):140-166, 1987) and Vincent and
Brown (Evolutionary game theory, natural selection, and darwinian dynamics.
Cambridge University Press, Cambridge, 2005). This principle essentially says
that the local gradient of invasion fitness ultimately determines the outcome of
the competition. However, as we will see in this paper, even if a system is
within the scope of IIS principle, its neighborhood always contains systems which
are beyond this scope. In this paper, in order to overcome such a limitation, we
establish a wider class of systems which is still reasonable as a model of
evolution of a species. For our wider class, the notion of raw invasion fitness
is introduced. In terms of raw invasion fitness, an explicit criterion for the
existence of generating function and a counterpart of IIS principle are obtained.
This enables us to discuss small perturbations of a system within or without the
scope of generating functions/IIS principle. Eventually, we understand why
invasion implies substitution, i.e. why the method using invasion fitness works
well with the existence of generating function, from our broader point of view.
PMID- 29961930
TI - Rectal Neuroendocrine Tumor with Synchronous Pancreatic Metastasis: A Case
Report.
AB - INTRODUCTION: Gastrointestinal neuroendocrine tumors (GI-NETs) often show
hematogenous metastasis, with the liver being the most common metastatic site;
however, metastasis to the pancreas is rare. CASE PRESENTATION: We report a rare
case of rectal NETs with pancreatic metastases in a 75-year-old man who presented
with a chief complaint of constipation. Imaging and endoscopic findings revealed
a rectal submucosal tumor, a pancreatic hypovascular mass, and multiple liver
masses. The rectal lesion and pancreatic lesions were diagnosed as neuroendocrine
tumors using biopsy and endoscopic ultrasound fine-needle aspiration,
respectively. Synchronous rectal NET and pancreatic NET (P-NET) with liver
metastasis of either of these two were preoperatively diagnosed. A two-stage
surgery was performed, comprising abdominoperineal resection and distal
pancreatectomy. Pre-operative imaging findings showed a solitary mass in the
pancreas, although the resected specimen contained multiple lesions.
Immunohistochemical staining of the resected rectal and pancreatic lesions showed
that both were synaptophysin positive and chromogranin A (CgA) negative.
Generally, rectal NET cells are positive for synaptophysin and negative for CgA,
while the majority of P-NETs are positive for both. The final diagnosis was
rectal NETs with pancreatic and liver metastases. Till date, there have been no
reports on the outcomes in patients with pancreatic metastasis of GI-NETs.
CONCLUSIONS: More case reports on metastatic NETs are needed to arrive at a
consensus for a standardized treatment regimen.
PMID- 29961931
TI - Qualitative Study on the Psychological Experiences of Trans-man and Trans-woman.
AB - Transsexuals have problems associated with self and gender identities, as well as
with their relationships with specialists such as doctor and counsellors. On the
basis of the principle of interpretative phenomenological analysis, an
exploratory research was carried out on self by studying the psychological
experiences of participants and their relationships with specialists.
Consequently the following needs of the transsexuals were identified: (1)
understanding and alleviation of grief, conflict, and anxiety associated with
gender dysphoria; (2) recovery and improvement of self-esteem; (3) support in
real-life experiences and measures related to social and legal issues, such as
coming out; and (4) necessity of information provision at medical institutions
and among peers. To meet these needs, it was suggested that the specialists
should (1) help recover their self-esteem through the exploration of their sexual
identities and maintain and improve their quality of life and (2) provide
comprehensive support to alleviate the grief caused by gender dysphoria. Such
support will facilitate affirmative psychological experiences of transsexuals,
which will require further attention in the form of clinical intervention.
PMID- 29961932
TI - Anesthetic Management in Tracheal Dilatation for Severe Tracheal Stenosis.
AB - We report the anesthetic management of a 65-year-old woman with recurrent, severe
tracheal stenosis who underwent tracheal dilatation. She had visited the
Department of Respiratory Medicine at our hospital for respiratory distress
approximately 20 years ago, and had undergone laser ablation under local
anesthesia. Because of recurrence and aggravation of respiratory distress, she
now presented at the Department of Thoracic Surgery, and was scheduled for
surgery. Percutaneous cardiopulmonary support was prepared, and she was sedated
with midazolam and dexmedetomidine. Under bronchoscopic guidance, a 5-mm
intubation tube was placed directly above the stenosis site. Laser ablation (by
argon plasma coagulation) and balloon dilatation were performed, and the tube was
replaced with one with a larger diameter, which was subsequently replaced with
another with an even larger diameter. Ultimately, a 7-mm tube was placed beyond
the stenosis site, and the operation was completed. After restoration of
spontaneous respiration and consciousness, the patient was extubated in the
operating room and returned to the intensive care unit. In anesthetic management
of patients with tracheal stenosis, treatment of hypoxia is important. In this
case, we collaborated with the attending physician, clinical engineers, and
operating room nurses throughout, and consequently, were able to perform the
operation safely.
PMID- 29961933
TI - Investigations into the Risk of Reproductive Toxicity Following Exposure to
Highly Active Anti-Retroviral Drugs in Rodents.
AB - With the introduction of Highly Active Antiretroviral Therapy (HAART), there has
been drastic decline in morbidity and mortality associated with HIV/AIDS.
However, many patients experience adverse drug reactions perhaps due to the
inherent toxic nature of HAART. The possible toxic effect of HAART (combination
ARVs) on reproduction and sexual dysfunction in seropositive HIV patients remains
a subject of intense research. This study was designed to investigate the toxic
effects of HAART on the reproductive hormones and organs of male and female rats.
Sexually mature adult male and female rats were administered therapeutic doses of
single and combination antiretroviral drugs for 48 days and thereafter sacrificed
under anaesthesia. Morphological and histopathological examination of the testes
and ovaries were carried out. Serum biochemical assay, semen quality analysis and
hormonal assays were also conducted using standard methods. Results show
significant (p < 0.05) reductions in the weight of testes and epididymis across
all groups versus control; sperm count and motility were also significantly
reduced in the test groups while hormonal analysis in males revealed significant
reductions in LH, FSH and Testosterone. In the females, there was a significant
(p < 0.05) reduction in the number of ovarian follicles, prolactin, estrogen and
progesterone. We thus conclude that the administration of single and combined
antiretroviral drugs have potential reproductive toxic effects.
PMID- 29961934
TI - Symptomatic Lacunar Infarct Accompanied with Posterior Reversible Encephalopathy
Syndrome: A Case Report.
AB - We present a 48-year-old man with a history of hypertension, who suddenly noticed
dysarthria and right hemiparesis. Diffusion-weighted MRI at 1 day after the onset
showed a small high-intensity region in the left corona radiata, indicating the
acute phase of lacunar infarction. Fluid attenuation inversion recovery images
showed extensive hyperintense lesions predominantly in the white matter of the
fronto-temporoparietal lobes and pons, indicating posterior reversible
encephalopathy syndrome (PRES). In addition, T2*-weighted gradient-echo images
showed multiple small round hypointense lesions in white matter and basal
ganglia, indicating cerebral microbleeds. This is a rare case of symptomatic
lacunar infarction accompanied with both PRES and microbleeds, which may suggest
that the pathophysiology of PRES is related to hypertension.
PMID- 29961935
TI - Clinical Reasoning in Kampo Education for Teaching Kampo Beginners.
AB - OBJECTIVES: Japanese traditional (Kampo) medicine has its own theories that are
quite different from those of Western medicine. For many students and medical
doctors, mastering it is a painstaking task. We examined the similarities in
clinical reasoning between Western and Kampo medicine, and developed an easy-to
understand method to teach Kampo theories enabling physicians to make accurate
diagnoses and choose suitable Kampo formulae. METHODS: We developed a teaching
method for Kampo medicine along clinical reasoning for beginners and evaluate its
availability and effectiveness in an actual team-based learning class. RESULTS: A
Kampo diagnostic procedure similar to that in Western medicine was developed. In
this method, some Kampo formulae, are chosen according to the chief complaint,
concomitant symptoms, characteristics, and distribution and exacerbation factors.
Subsequently, from a point of view of the chosen Kampo formulae, patients' signs
and symptoms are matched to find the most suitable formula. Students chose the
same suitable formula among 6 groups and gained confidence to choose the correct
Kampo formulae. CONCLUSIONS: A new Kampo educational method was developed that
raises students' and physicians' confidence in making diagnoses and prescribing
Kampo medicines.
PMID- 29961937
TI - Augmented-reality computed tomography-guided transcatheter pacemaker implantation
in dextrocardia and congenitally corrected transposition of great arteries.
PMID- 29961936
TI - Clinical Application of High-pitched Breath Sound in Children with Asthma.
AB - OBJECTIVE: Breath sound parameters have been suggested to be a new biomarker of
airway conditions in asthmatic patients. We investigated new breath sound
parameters to determine their utility for evaluating asthmatic children. METHODS:
Fifty-seven children (mean age, 9.0 years, 6-16 years) were included in the
present study. The new breath sound parameters, the area under the curve
(AUC)>1,000 Hz (A1000 [dBm.Hz]) and the ratio of the A1000 to the total AUC at
100 Hz to the highest frequency of the dBm power spectrum (AT) (A1000/AT [%])
were measured before and after beta2 agonist inhalation. Spirography and the
forced oscillation technique were also used to evaluate all subjects. RESULTS:
The value of A1000 was negatively correlated with the FEV1 (p=0.028). The
increase in the DeltaFEV1 was correlated with the decrease in the DeltaA1000
(p=0.001) and the DeltaA1000/AT (p=0.036). CONCLUSIONS: The A1000 indicates the
airway condition, and the DeltaA1000 and the DeltaA1000/AT well describe the
dilatation of the airways. These parameters are useful for the assessment of
bronchial reversibility in asthmatic children.
PMID- 29961938
TI - Fractional flow reserve and intravascular scan as part of the coronary fistulas
diagnostic process: Future perspectives.
PMID- 29961939
TI - A complex valve anatomy for Mitraclip: Forme fruste of Barlow's disease with
cleft.
PMID- 29961940
TI - Right and left-sided carcinoid heart disease.
PMID- 29961941
TI - Adult woman with giant thrombosed multiple coronary aneurysms.
PMID- 29961943
TI - Biting down on the truth: A case of a delayed hypersensitivity reaction to
lidocaine.
PMID- 29961942
TI - Life-threatening complication of untreated coarctation of the aorta in a teenager
solidified in a three-dimensional printed cardiovascular model.
PMID- 29961944
TI - Viral glycoproteomes: technologies for characterization and outlook for vaccine
design.
AB - It has long been known that surface proteins of most enveloped viruses are
covered with glycans. It has furthermore been demonstrated that glycosylation is
essential for propagation and immune evasion for many viruses. The recent
development of high-resolution mass spectrometry techniques has enabled
identification not only of the precise structures but also the positions of such
post-translational modifications on viruses, revealing substantial differences in
extent of glycosylation and glycan maturation for different classes of viruses.
In-depth characterization of glycosylation and other post-translational
modifications of viral envelope glycoproteins is essential for rational design of
vaccines and antivirals. In this Review, we provide an overview of techniques
used to address viral glycosylation and summarize information on glycosylation of
enveloped viruses representing ongoing public health challenges. Furthermore, we
discuss how knowledge on glycosylation can be translated to means to prevent and
combat viral infections.
PMID- 29961945
TI - Prevalence of low back pain and associated factors among nurses in Jordan.
AB - BACKGROUND: Low back pain (LBP) is a significant work-related problem, especially
among nurses. This is due to its high prevalence and impact on the healthcare
system, either directly through treating affected nurses, or indirectly through
the decrease in nurses' productivity. AIM: The aim of this study is to measure
the prevalence rates of LBP among nurses in Jordan, and to uncover the associated
factors and consequences. METHODS: A cross-sectional design study. Data were
collected through a data collection sheet, developed based on literature, from
seven public hospitals and one university hospital over a period of 2 months.
RESULTS: A total of 384 nurses completed the data sheet with a response rate of
76.8%. Current prevalence of LBP was 69% (n = 265), 1-year prevalence was 78.9%
(n = 303), while accumulative prevalence was 83.6% (n = 321). Factors associated
with LBP were older age, female gender, being overweight, and having longer
experience in nursing; 40% of nurses agreed that the LBP increased their number
of sick leaves, 58.7% agreed it lowered their productivity, and 9% reported that
it forced them to change unit. CONCLUSION: LBP is a significant work-related
problem among Jordanian nurses, with high-prevalence rates, and debilitating
medical and professional consequences. Interdisciplinary efforts are needed to
reduce these consequences.
PMID- 29961946
TI - A copula model for joint modeling of longitudinal and time-invariant mixed
outcomes.
AB - Motivated by a preclinical study in a mouse model of breast cancer, we suggest a
joint modeling framework for outcomes of mixed type and measurement structures
(longitudinal versus single time/time-invariant). We present an approach based on
the time-varying copula models, which is used to jointly model longitudinal
outcomes of mixed types via a time-varying copula, and extend the scope of these
models to handle outcomes with mixed measurement structures. Our framework allows
the parameters corresponding to the longitudinal outcome to be time varying and
thereby enabling researchers to investigate how the response-predictor
relationships change with time. We investigate the finite sample performance of
this new approach via a Monte Carlo simulation study and illustrate its
usefulness by an empirical analysis of the motivating preclinical study,
comparing the effect of various treatments on tumor volume (longitudinal
continuous response) and the number of days until tumor volume triples (time
invariant count response). Through the real-life application and the simulation
study, we demonstrate that, compared with marginal modeling, the joint modeling
framework offers more precision in the estimation of model parameters.
PMID- 29961947
TI - Gastrointestinal: Huge submucosal hematoma of the stomach arising in a patient
with vascular type Ehlers-Danlos syndrome.
PMID- 29961948
TI - "A tool doesn't add anything". The importance of added value: Use of
observational pain tools with patients with advanced dementia approaching the end
of life-a qualitative study of physician and nurse experiences and perspectives.
AB - BACKGROUND: Observational pain tools (OPTs) are widely recommended in health care
policies, clinical guidelines, and recommendations for pain assessment and
management. However, it is unclear whether and how these tools are used for
patients with advanced dementia approaching the end of life. AIM: To explore
hospice, secondary, and primary care physicians' and nurses' use of OPTs with
patients dying with advanced dementia and their perspectives on practice
development and training needs. METHODS: Twenty-three physicians and 24 nurses
with experience of caring for people dying with advanced dementia were recruited
from primary care surgeries (n = 5), hospitals (n = 6), hospices (n = 4), and
nursing homes (n = 10). Semistructured, face-to-face interviews were conducted.
Interviews were digitally recorded, transcribed verbatim, and thematic analysis
applied to identify core themes. RESULTS: Three key themes emerged: (1) use of
OPTs in this vulnerable patient population, (2) barriers to the use of OPTs and
lack of perceived "added value", and (3) perspectives on practice development and
training in pain assessment in advanced dementia at end of life. Just over one
quarter of participants (n = 13) routinely used OPTs. Reasons for nonuse included
perceived limitations of such tools, difficulties with their use and integration
with existing practice, and lack of perceived added value. Most participants
strongly emphasised a need for ongoing training and development which facilitated
transfer of knowledge and multidisciplinary skills across professions and
specialties. CONCLUSIONS: Health professionals require ongoing support in
developing and integrating change to existing pain assessment protocols and
approaches. These findings have important implications for health education,
practice, and policy.
PMID- 29961949
TI - Alterations in brain microstructure in rats that develop abnormal aggression
following peripubertal stress.
AB - Exposure to early adversity is implicated in the development of aggressive
behaviour later in life in some but not all individuals. The reasons for the
variability in response to such experiences are not clear but may relate to pre
existing individual differences that influence their downstream effects. Applying
structural magnetic resonance imaging (MRI) to a rat model of abnormal aggression
induced by peripubertal stress, we examined whether individual differences in the
development of an aggressive phenotype following stress exposure were underpinned
by variation in the structure of aggression-associated, corticolimbic brain
regions. We also assessed whether responsiveness of the hypothalamic-pituitary
adrenal axis to stress was associated with neurobehavioural outcome following
adversity. A subset of the rats exposed to peripubertal stress developed an
aggressive phenotype, while the remaining rats were affected in other behavioural
domains, such as increased anxiety-like behaviours and reduced sociability.
Peripubertal stress led to changes in tissue microstructure within prefrontal
cortex, amygdala and hippocampal formation only in those individuals displaying
an aggressive phenotype. Attenuated glucocorticoid response to stress during
juvenility predicted the subsequent development of an aggressive phenotype in
peripubertal stress-exposed rats. Our study establishes a link between
peripubertal stress exposure in rats and structural deviations in brain regions
linked to abnormal aggression and points towards low glucocorticoid
responsiveness to stress as a potential underlying mechanism. We additionally
highlight the importance of considering individual differences in behavioural
response to stress when determining neurobiological correlates.
PMID- 29961950
TI - Rosacea-like demodicosis and papulopustular rosacea may be two phenotypes of the
same disease, and pityriasis folliculorum may be their precursor: response to the
comment of Tatu.
PMID- 29961951
TI - Compliance with perioperative prophylaxis guidelines and the use of novel outcome
measures.
AB - Postoperative wound infections represent an important source of morbidity and
mortality in children. Perioperative antibiotic prophylaxis has been shown to
decrease the risk of developing infections and hospital guidelines surrounding
antibiotic use exist to standardize patient care. Despite supporting evidence,
rates of compliance with guidelines vary. Quality improvement initiatives have
been introduced to improve compliance with intraoperative antibiotic guidelines.
Thorough infection surveillance, including antibiotic provision in presurgical
checklists, computerized voice antibiotic administration prompts, and national
feedback systems are now increasingly common. Few studies have been conducted
investigating the effectiveness of prophylactic antibiotics in children. Outcome
measures such as morbidity and mortality and return to the operating room can be
used to examine the relationship between antibiotic use and patient outcome but
these measures are limited in that they occur infrequently or are subjective and
difficult to measure. Metrics such as days alive out of hospital and length of
hospital stay may be useful alternatives for ongoing monitoring of infections and
identifying improvements in patient outcomes. Guidelines on antibiotic
prophylaxis have facilitated an increase in the correct provision of
perioperative antibiotics and a reduction in the incidence of postoperative
infection. Measures of patient outcome such as days alive out of hospital and
length of hospital stay are easy to collect and calculate but further work is
needed to confirm the utility of these measures for monitoring infection rates.
PMID- 29961952
TI - Investigating the Effect of Different Surface Treatments on Vickers Hardness and
Flexural Strength of Zirconium and Lithium Disilicate Ceramics.
AB - PURPOSE: To investigate the effect of different surface treatments on Vickers
hardness and flexural strength of zirconia and lithium disilicate ceramics.
MATERIALS AND METHODS: 50 zirconia and 50 lithium disilicate ceramic specimens
were used. After identifying one group as the control, grinding, sandblasting,
CoJet, and Er:YAG laser were applied on the surface of specimens (n = 10). After
applying Vickers hardness test to specimens, flexural strength test was
performed. The data were analyzed with two-way ANOVA and Duncan's multiple
comparisons tests. RESULTS: There were statistically significant differences
found between surface treatment groups in terms of Vickers hardness of zirconia
and lithium disilicate ceramics (p < 0.001), but there were no statistically
significant differences found between surface treatment groups in terms of
flexural strength (p > 0.05). CONCLUSIONS: Surface treatments could affect the
hardness of ceramics. Therefore, was zirconia found to be harder and more durable
than lithium disilicate ceramics.
PMID- 29961953
TI - Impact of blood transfusion on outcomes following resection for colorectal liver
metastases in the modern era.
AB - BACKGROUND: Evidence suggests that perioperative blood loss and blood
transfusions are associated with poorer long-term outcomes in patients undergoing
other oncological surgery. The aim of this study was to determine the long-term
outcomes of patients requiring a blood transfusion post-hepatectomy for
colorectal liver metastases (CRLM). METHODS: This is a retrospective review from
2005 to 2012. Overall survival (OS) and recurrence-free survival (RFS) were
assessed using Kaplan-Meier curves. Red blood cell transfusion (RBCT) and other
clinic-pathological parameters were handled as covariates for Cox regression
analysis. RESULTS: Six hundred and ninety patients were included. Median follow
up was 33 months. Sixty-four (9.3%) patients required a perioperative RBCT. RBCT
was a predictor for decreased OS (median 41 versus 49 months, P = 0.04). However,
on multivariate regression analyses preoperative chemotherapy, post-operative
complications and Clinical Risk Score were independently associated with reduced
OS, though RBCT was not. There was no association between RBCT and RFS (median 15
versus 17 months, P = 0.28). CONCLUSIONS: RBCT is not independently associated
with a poorer OS.
PMID- 29961954
TI - Direct Imaging for Single Molecular Chain of Surfactant on CeO2 Nanocrystals.
AB - Organic surfactant controls the synthesis of nanocrystals (NCs) with uniform size
and morphology by attaching on the surface of NCs and further facilitates their
assembly into ordered superstructure, which produces versatile functional
nanomaterials for practical applications. It is essential to directly resolve the
surfactant molecules on the surface of NCs to improve the understanding of
surface chemistry of NCs. However, the imaging resolution and contrast are
insufficient for a single molecule of organic surfactant on NCs. In this work,
direct characterization of organic surfactant on CeO2 NCs is conducted by using
the state-of-the-art aberration corrected scanning transmission electron
microscopy (STEM) imaging and electron energy loss spectra (EELS) techniques. The
explicit evidence for the existence and distribution of organic surfactant on
CeO2 NCs are obtained on the atomic scale by EELS elemental mapping. Besides,
STEM imaging parameters are systematically adjusted and optimized for the direct
imaging of a single molecular chain of organic surfactant on CeO2 NCs. Such
direct visualization of organic surfactant molecule on the surface of NCs can be
a significant step forward in the fields of nanomaterials surface chemistry and
materials characterization.
PMID- 29961955
TI - Stage selection for neoadjuvant radiotherapy in non-cervical esophageal cancer: A
propensity score-matched study based on the SEER database.
AB - BACKGROUND: The effect of neoadjuvant radiotherapy (NRT) was controversial in non
cervical esophageal cancer. The aim of this study was to identify which stage of
non-cervical esophageal cancer would get benefit from NRT using propensity score
matching (PSM) and survival analysis based on the Surveillance Epidemiology, and
End Results (SEER) database. METHODS: A selection process was used for case
screening from the SEER database. Seven baseline variables were included in PSM.
The survival analysis were based on T stage (T2 and T3 ) and status of lymph node
involvement (N0 and N+ ) using Kaplan-Meier method and log-rank test for
comparing the overall survival of patient with NRT plus surgery versus those who
with surgery alone (SA). RESULTS: A total of 1631 cases were included in this
study. After PSM, 225 cases of esophageal squamous cell carcinoma (ESCC) and 606
cases of esophageal adenocarcinoma (EAC) were enrolled in survival analysis. We
found that only T3 N+ stage of EAC would got survival benefit from NRT (P =
0.0052), while NRT showed no significant benefit in overall survival in other
stages of EAC and ESCC. CONCLUSIONS: NRT followed by resection had a significant
survival benefit in non-cervical EAC patients with T3 N+ stage. For patients with
ESCC and other EAC stages, NRT versus SA did not demonstrate a statistical
significant survival difference.
PMID- 29961956
TI - Vulvo-vaginal lichen planus: A focussed review for the clinician.
AB - Vulvo-vaginal lichen planus is a condition which imposes a significant burden of
symptoms and sequale. There is a paucity of knowledge and evidenced-based
management with significant diagnostic delay prior to appropriate treatment being
common. There remains great variability in clinician practice in the context of
limited knowledge. This clinical review presents current evidence on the
clinicopathological features, practical assessment and management options.
Learning points include characterization of this chronic, burdensome clinical
entity that has no standardized diagnostic or management protocols. We provide
practical clinical conclusions based on current knowledge and identify areas for
future research to improve patient outcomes.
PMID- 29961957
TI - Retirement: A concept for nurses to consider.
AB - PROBLEM: The large number of aging retirees is changing the landscape of US
healthcare and economic systems. Many nurses will be among these retirees. While
retirement has been studied in many fields, it has been explored considerably
less in nursing science. Retirement as a concept is complex, not well-defined
across disciplines, and the impact of this important transition on health and
well-being is not well-understood. PURPOSE: The purpose of this article is to
explore the concept of retirement as a transition that may be related to health
and well-being in aging individuals. FINDINGS: Conceptual exploration supports
that retirement is defined by two identified attributes: (a) It is a transitional
period surrounding stopping or changing full or part-time, paid or unpaid
employment status, and (b) it occurs at a time when a person self-identifies as
being retired. Identified antecedents and consequences of retirement are closely
related to health. CONCLUSION: Many life changes often occur during the
transition of retirement. As a concept, retirement is linked to healthy,
transitional aging. Nursing's holistic perspective of addressing client needs can
be better understood when caring for individuals who have retired or are planning
to retire.
PMID- 29961958
TI - Mitochondrial dysfunction and altered ribostasis in hippocampal neurons with
cytoplasmic inclusions of multiple system atrophy.
AB - Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative
disease. It has recently been shown that patients with MSA accompanied by
cognitive decline display numerous neuronal cytoplasmic inclusions (NCIs) in the
limbic neurons. We examined potential mechanisms underlying the formation of
these NCIs by determining of mitochondrial function and statuses of RNA
processing by analyzing 12 pathologically confirmed cases of MSA. Among them,
four had cognitive impairment Semiquantitative evaluation using
immunohistochemistry analyses revealed a significantly greater NCI burden in the
hippocampal cornu ammonis 1 (CA1) subfield, subiculum, and amygdala in the cases
with cognitive impairments compared with those without cognitive impairment.
Immunofluorescent staining revealed that limbic neurons with NCIs often
accelerated production of reactive oxygen species (ROS) and degraded
mitochondrial quality control. Immunofluorescent staining also revealed that
neurons with these NCIs translocated heterogeneous nuclear ribonucleoprotein A1
(HNRNPA1) from the nucleus and aggregated abnormally at the perinuclear rim.
Since the NCIs in the hippocampal neurons of MSA with cognitive impairments were
more numerous, the neuronal mitochondrial dysfunction and altered ribostasis
observed in NCI formation may be involved in the hippocampal degeneration of MSA.
PMID- 29961959
TI - Natural selection for body shape in resource polymorphic Icelandic Arctic charr.
AB - Resource polymorphisms exhibit remarkable intraspecific diversity and in many
cases are expected to be maintained by diversifying selection. Phenotypic trade
offs can constrain morphologically intermediate individuals from effectively
exploiting both alternate resources, resulting in ecological barriers to gene
flow. Determining if and how phenotypic trade-offs cause fitness variation in the
wild is challenging because of phenotypic and environmental correlations
associated with alternative resource strategies. We investigated multiple
pathways through which morphology could affect organismal performance, as
measured by growth rate, and whether these effects generate diversifying
selection in polymorphic Icelandic Arctic charr (Salvelinus alpinus) populations.
We considered direct effects of morphology on growth and indirect effects via
trophic resource use, estimated by stable isotopic signatures, and via parasitism
associated with trophic resources. We sampled over 3 years in (lakes)
Thingvallavatn and Vatnshlidarvatn using the extended selection gradient path
analytical approach and estimating size-dependent mortality. We found evidence
for diversifying selection only in Thingvallavatn: more streamlined and
terminally mouthed planktivore charr experienced greater growth, with the
opposite pattern in small benthic charr. However, this effect was mediated by
parasitism and nontrophic pathways, rather than trophic performance as often
expected. Detection of between-morph differences in the presence
(Vatnshlidarvatn) and direction (Thingvallavatn) of size-dependent mortality,
together with nontrophic effects of shape, suggests that a morphological trophic
performance explanation for polymorphism is insufficient. This rare insight into
selection during early diversification suggests that a complex of interacting
local factors must be considered to understand how phenotype influences fitness,
despite morphological variation reflecting intuitive trade-off explanations.
PMID- 29961960
TI - An NIR-Fluorophore-Based Therapeutic Endoplasmic Reticulum Stress Inducer.
AB - The endoplasmic reticulum (ER) stress signaling or unfolded protein response
(UPR) is a common feature of many human diseases, including cancer. Excessive
activation of ER stress directly induces cell death, holding a new promising
strategy for the therapeutic intervention of cancer. Current ER-stress-inducing
agents mainly target UPR components or proteasomes, which exert limited treatment
efficacy and undesired side effects due to unselective ER stress and poor tumor
specific distribution. In this study, a unique near-infrared (NIR) fluorophore,
IR-34, is synthesized and identified to selectively and efficiently trigger
tumoricidal ER stress by targeting the mitochondrial protein NDUFS1. IR-34 is
demonstrated to specifically accumulate in living cancer cells for tumor NIR
imaging and drastically inhibit tumor growth and recurrence without causing
apparent toxicity. Thus, this multifunctional NIR fluorophore may represent a
novel theranostic agent for tumor imaging-guided treatment and also strengthens
the idea that mitochondria could be a useful target for therapeutic ER stress in
cancer cells.
PMID- 29961961
TI - Group cognitive-behavioural treatment with long-term follow-up and targeting self
identity for hoarding disorder: An open trial.
AB - BACKGROUND: Group cognitive-behavioural therapy (G-CBT) for hoarding disorder
(HD) may be an intervention of choice, considering its efficacy, low costs, and
impact on comorbid anxiety and depression. But although G-CBT and modifications
of G-CBT have been applied, none has assessed G-CBT efficacy at follow-up. In the
current open-label pilot study, we tested the efficacy of G-CBT at posttreatment
and 6-month follow-up and whether the inclusion of targeted reasoning and self
identity components added to G-CBT efficacy. METHODS: Participants (n = 16) with
the HD according to the DSM-5 criteria without major comorbid conditions and not
requiring immediate medical intervention were retained. The intervention included
a 20-week G-CBT with the inclusion of modules on reasoning and self-identity.
RESULTS: Very large/large effect sizes, depending on the outcome measure, were
observed at posttreatment. Also, HD severity decreased from posttreatment to 6
month follow-up. All participants showed reliable change from pretreatment to
follow-up. CONCLUSIONS: The results emphasize the efficacy of G-CBT with
additional targeted reasoning and self-components.
PMID- 29961962
TI - Pre-adolescent children's experiences of receiving diabetes-related support from
friends and peers: A qualitative study.
AB - BACKGROUND: While pre-adolescent children with type 1 diabetes receive most
support from their parents/caregivers, others also contribute to their care. This
study explored pre-adolescent children's experiences of receiving diabetes
related support from friends and peers. The objective was to identify how
children could be better supported by their friends and peers to undertake
diabetes self-management. METHODS: In-depth interviews with 24 children (aged 9
12 years) with type 1 diabetes. Data were analysed using an inductive, thematic
approach. RESULTS: Children gave mixed accounts of their experiences of speaking
to their school/class about diabetes with some indicating that this had resulted
in unwanted attention. Most individuals reported that other children had a
limited understanding of diabetes and sometimes acted in insensitive ways or said
things they found upsetting. Virtually all children described having a small
number of close friends who were interested in learning about diabetes and
provided them with support. These friends provided support in three overlapping
ways, as "monitors and prompters," "helpers" and "normalizers." While some
children described benefiting from meeting peers with type 1 diabetes, most
indicated that they would prefer to develop friendships based on shared interests
rather than a common disease status. DISCUSSION AND CONCLUSIONS: Friends and
peers provide several kinds of support to pre-adolescent children with diabetes.
Health professionals could consider ways to assist small friendship groups to
undertake monitoring and prompting, helping and normalizing roles. Parents,
schools and health professionals could explore ways to normalize self-management
practices to better support children with diabetes in school settings.
PMID- 29961963
TI - First reported implementation of a German-language progress test in an
undergraduate dental curriculum: A prospective study.
AB - INTRODUCTION: Progress testing is a special form of longitudinal and feedback
oriented assessment. Even though well established in human medical curricula,
this is not the case in dental education. The aim was the prospective development
and implementation of the first reported German-language Dental Progress Test
(DPT) for the undergraduate dental curriculum at the Medical University of Graz,
Austria. MATERIAL AND METHODS: Participation in DPT was compulsory for all dental
students in terms 7-12 (years 4-6). Three tests, each consisting of 100 items out
of a pool of 375, were administered within 3 consecutive terms in 2016 and 2017.
Rasch analyses were used to evaluate the questionnaire and identify misfitting
items. RESULTS: In the item responses, 59.7% were "correct," 27.0% were "false"
and 13.3% were answered with "don't know," with similar results at all 3 time
points. The assumption of parallel ICC was met (T1: chi2 = 51.071, df = 74, P =
.981; T2: chi2 = 57.044, df = 67, P = .802; T3: chi2 = 58.443, df = 72, P =
.876) and item difficulties for the thematic fields were similarly distributed
across the latent dimensions. CONCLUSION: The newly introduced DPT is appropriate
for testing dental students and is well balanced for the tested target group.
PMID- 29961964
TI - Prognostic significance of histopathology in canine anal sac gland
adenocarcinomas: Preliminary results in a retrospective study of 39 cases.
AB - Metastatic rates and survival times of canine anal sac gland adenocarcinomas
(ASGACs) vary among studies, making prognostication difficult. Little is known
about the prognostic significance of histopathology of ASGACs. This retrospective
study investigated associations between histological features, clinical
presentation and outcome for 39 ASGACs. Most tumours were incompletely excised
(62%) and had moderate to marked peripheral infiltration (74%). The predominant
growth pattern was solid, tubules/rosettes/pseudorosettes and papillary in 49%,
46% and 5% of the cases, respectively. Nuclear pleomorphism was either moderate
(77%) or mild (23%). Necrosis and lymphovascular invasion were present in 54% and
10% of the cases, respectively. All histological features except mitotic count
and necrosis were associated with nodal metastasis at presentation. A
statistically significant poorer outcome was identified for tumours with a solid
growth pattern, moderate or marked peripheral infiltration, necrosis and
lymphovascular invasion. These results need further validation in a larger cohort
of dogs.
PMID- 29961965
TI - COMP Report: CPQR Technical Quality Control Guidelines for Data Management
Systems.
AB - The Canadian Organization of Medical Physicists (COMP), in close partnership with
the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series
of Technical Quality Control (TQC) guidelines for radiation treatment equipment.
These guidelines outline the performance objectives that equipment should meet in
order to ensure an acceptable level of radiation treatment quality. The TQC
guidelines have been rigorously reviewed and field tested in a variety of
Canadian radiation treatment facilities. The development process enables rapid
review and update to keep the guidelines current with changes in technology (the
most updated version of this guideline can be found on the CPQR website). This
particular TQC details recommended quality control testing of radiation data
management systems.
PMID- 29961966
TI - Clinical skills as a vehicle for interprofessional learning.
PMID- 29961967
TI - Identification of seven novel HLA class I and II alleles.
AB - Seven novel alleles were identified using two next generation sequencing
technologies. Three alleles were confirmed.
PMID- 29961968
TI - Reinforcement uncertainty enhances preference for choice in humans.
AB - Under concurrent-chains schedules of reinforcement, participants often prefer
situations that allow selection among alternatives (free choice) to situations
that do not (forced choice). The present experiment examined the effects of
reinforcement probability on choice preferences. Preferences for free versus
forced choice were measured under a condition in which participants' choices were
always reinforced (reinforcement probability of 1.0) and a condition in which
outcomes were uncertain (reinforcement probability of 0.5). Forty-four college
students participated and preferences were examined under a concurrent-chains
schedule of reinforcement. Participants preferred free choice under uncertain
reinforcement, but a bias toward free choice was not observed when reinforcement
was certain. These results align with previous findings of preference for free
choice under conditions of uncertainty, but suggest that preference may be
dependent upon probabilistic reinforcement contingencies in the terminal links of
the concurrent-chains arrangement. Thus, reinforcement probability is an
important variable to consider when conducting similar studies on the value of
choice.
PMID- 29961969
TI - An updated phylogeny of the redlip blenny genus Ophioblennius.
AB - An updated molecular phylogeny of the blenny genus Ophioblennius, with a focus on
two geographically disjunct morphotypes observed in Brazil, is presented. The
analyses showed that specimens from the north-eastern Brazilian coast are the
endemic redlip blenny Ophioblennius trinitatis, but specimens from the southern
Brazilian coast are conspecific to an undescribed east Atlantic Ocean (Gulf of
Guinea) species, previously unknown in Brazil. Possible explanations for this
geographical pattern include: natural larval dispersal and rafting across the
Atlantic; an unknown ecological attribute that enabled this species to colonize
southern Brazil; oil platforms as introduction vectors.
PMID- 29961970
TI - Application of Saccharomyces cerevisiae var. boulardii in food processing: a
review.
AB - Probiotics are increasingly being added to food in order to develop products with
health-promoting properties. Particularly, Saccharomyces cereviceae var.
boulardii yeast is recently being investigated like a starting-culture for
development of functional and probiotic foods. Although the literature is
abundant on the beneficial effects of S. boulardii on health, slight information
is available on the effects of supplementing this probiotic to food systems. The
aim of this paper is to examine the applications of S. boulardii to different
food matrices and its implication in food processing (stability, sensorial
properties and other technological implications) and the concomitant effects on
nutrition and health.
PMID- 29961971
TI - Staged repair of thoracoabdominal aneurysm with infra-renal elephant trunk graft.
AB - A patient with residual thoracoabdominal aortic aneurysm and chronic dissection
extending into the branch iliac arteries underwent staged open and endovascular
repair. Open repair of the reno-visceral segment was performed with an "elephant
trunk" trunk graft placed distally into a 12-cm infra-renal aorta. One month
later, the patient underwent a successful completion endovascular aortic repair.
This case demonstrates the utility of combining traditional and endovascular
surgery to manage complex aortic pathologies.
PMID- 29961972
TI - Comparison between May-Grunwald-Giemsa and rapid cytological stains in fine
needle aspirates of canine mast cell tumour: Diagnostic and prognostic
implications.
AB - Mast cell tumours (MCTs) are often diagnosed by cytology based on the
identification of purple intracytoplasmic granules with methanolic Romanowsky
stains, including May-Grunwald-Giemsa (MGG). In clinical practice, aqueous rapid
stains (RS) are commonly used, but mast cell granules may not stain properly. Aim
of this prospective study was to investigate the frequency of MCT hypogranularity
with RS and its potential implications in tumour identification, cytological
grading assessment and recognition of nodal metastatic disease. Cytological
preparations of canine primary MCTs and metastatic lymph nodes with subsequent
histopathological confirmation were included. For each case, good-quality smears
were stained with both MGG and RS and comparatively assessed. Eleven of 60
(18.3%) primary MCTs were hypogranular with RS; 9 of them were histologically
high-grade tumours and in 3 cases (5%) a definitive MCT diagnosis could not be
made. Accuracy in cytological grading assessment (85%) did not differ between RS
and MGG. Thirteen of 28 (46.4%) metastatic lymph nodes were hypogranular with RS
and 3 independent observers failed to identify nodal MCT metastases in 7% to 18%
of RS-stained smears. This study confirms that, in limited cases, RS can be
ineffective in staining MCT granules, particularly in high-grade tumours, thus
making diagnosis more dependent on experience and quality of preparations. In
dubious cases, methanolic stains should be applied. The use of RS is discouraged
for the search of nodal metastases, as the identification of isolated mast cells
can be more challenging.
PMID- 29961974
TI - Topical timolol: An effective treatment option for agminated pyogenic granuloma.
AB - We present three patients with agminated pyogenic granulomas who experienced
significant decrease in size and bleeding with treatment with topical timolol
solution with minimal side effects. One patient had complete clinical resolution.
For patients with agminated pyogenic granuloma who may otherwise have limited
treatment options, timolol is an effective potential solution.
PMID- 29961973
TI - Appreciative management assessed by physiotherapists working in public or private
sector: A cross-sectional study.
AB - PURPOSE: To describe how appreciative management occurs in the working
environment of physiotherapists. METHODS: Cross-sectional survey. The data was
collected with an electronic questionnaire. The survey instrument was
Appreciative Management Scale. The participants were 474 physiotherapists working
in clinical or managerial positions from public or private sector. RESULTS:
Appreciative management was realized on an average level within physiotherapy.
The highest scoring dimension was Equality and the weakest was Systematic
Management. Appreciative management and all of its four categories were
associated with the management education received by the manager, the
respondent's position, and his or her current duties. The dimension of
Appreciation of Know-how and its subdimensions of Guidance and Autonomy were
recognized more often when the manager's basic training was in physiotherapy
rather than another field. CONCLUSIONS: It is important that managers in
physiotherapy recognize the characteristics of appreciative management, so they
can include them as part of their good practice and as part of their own
leadership style. Managers in physiotherapy need to be encouraged to participate
in management education and also enable the participation of others. A background
in physiotherapy can be seen to further the practice and development of
physiotherapy. Offering physiotherapists challenging assignments and enabling
their career development in physical therapy units is therefore of great
importance.
PMID- 29961975
TI - A randomized, open-label, multicentre, parallel-controlled study comparing the
efficacy and safety of biphasic insulin aspart 30 plus metformin with biphasic
insulin aspart 30 monotherapy for type 2 diabetes patients inadequately
controlled with oral antidiabetic drugs: The merit study.
AB - AIM: To confirm non-inferiority of biphasic insulin aspart 30 (BIAsp 30) plus
metformin to BIAsp 30 in lowering glycated haemoglobin (HbA1c) in Chinese
patients with inadequately controlled type 2 diabetes using oral antidiabetic
drugs. MATERIALS AND METHODS: In this 16-week, prospective, randomized, open
label, multicentre, parallel-controlled study, patients aged 18-79 years with
HbA1c >=7% were randomized to BIAsp 30 plus metformin (n = 130) or BIAsp 30 (n =
127). Initially, 500 mg metformin was administered twice daily and BIAsp 30 was
administered at 0.2-0.3 U/kg/d. Changes in HbA1c % from baseline to week 16 as
well as secondary and safety endpoints were assessed. RESULTS: In total, 83.66%
of patients in the BIAsp 30 plus metformin (n = 110) and the BIAsp 30 (n = 105)
groups completed the study. Mean (+/-standard deviation) change in HbA1c from
baseline to endpoint was -1.74 +/- 1.64% and -1.32 +/- 2.05% with BIAsp 30 plus
metformin and BIAsp 30, respectively. Least squares mean treatment difference was
-0.67% (95% CI, -1.06; -0.28). The upper limit of the 95% CI was <0.4 (non
inferiority margin). A significantly higher proportion of individuals reached
HbA1c <7% with BIAsp 30 plus metformin than with BIAsp 30 (53.15% vs 35.19%; P =
0.0074). At endpoint, daily BIAsp 30 dose (P < 0.001) and weight gain were
significantly lower (P < 0.05) in the BIAsp 30 plus metformin group compared with
the BIAsp 30 group. No between-group differences in number of hypoglycaemic
events were observed. CONCLUSION: BIAsp 30 plus metformin was non-inferior to
BIAsp 30 in safely reducing HbA1c in this study.
PMID- 29961976
TI - Metal-Free Halogen(I) Catalysts for the Oxidation of Aryl(heteroaryl)methanes to
Ketones or Esters: Selectivity Control by Halogen Bonding.
AB - Metal-free halogen(I) catalysts were used for the selective oxidation of
aryl(heteroaryl)methanes [C(sp3 )-H] to ketones [C(sp2 )=O] or esters [C(sp3 )
O]. The synthesis of ketones was performed with a catalytic amount of NBS in DMSO
solvent. Experimental studies and density functional theory (DFT) calculations
supported the formation of halogen bonding (XB) between the heteroarene and N
bromosuccinimide, which enabled imine-enamine tautomerism of the substrates. No
additional activator was required for this crucial step. Isotope-labeling and
other supporting experiments suggested that a Kornblum-type oxidation with DMSO
and aerobic oxygenation with molecular oxygen took place simultaneously. A
background XB-assisted electron transfer between the heteroarenes and halogen(I)
catalysts was responsible for the formation of heterobenzylic radicals and, thus,
the aerobic oxygenation. For selective acyloxylation (ester formation), a
catalytic amount of iodine was employed with tert-butyl hydroperoxide in
aliphatic carboxylic acid solvent. Several control reactions, spectroscopic
studies, and Time-Dependent Density Functional Theory (TD-DFT) calculations
established the presence of acetyl hypoiodite as an active halogen(I) species in
the acetoxylation process. With the help of a selectivity study, for the first
time we report that the strength of the XB interaction and the frontier orbital
mixing between the substrates and acyl hypoiodites determined the extent of the
background electron-transfer process and, thus, the selectivity of the reaction.
PMID- 29961978
TI - Integrating behavioral health in the pediatric medical home.
AB - TOPIC: Behavioral health disorders (psychiatric illness and substance abuse
disorders) represent a significant burden across the nation's health care system.
The number of children and adolescents requiring behavioral health care has
increased while at the same time the behavioral health workforce continues to
experience a shortage of providers. The current model of care is failing to meet
the behavioral health needs of children and adolescents. Initiatives are underway
that call for improved integration of behavioral health services into primary
care. Patients and families often seek behavioral health care in the primary care
setting. PURPOSE: The purpose of this article is to describe how one large urban
pediatric practice began to integrate behavioral health services. Opportunities
and challenges are discussed along with a review of three integrated care
delivery models. SOURCES USED: Literature search was performed using PubMed and
CINAHL; we also used Substance Abuse and Mental Health Services Administration,
American Academy of Child and Adolescent Psychiatry, and American Academy of
Pediatrics Guidelines, which describe the need for integration of
behavioral/mental health into pediatric primary care.
PMID- 29961977
TI - The association between acute malnutrition and water, sanitation, and hygiene
among children aged 6-59 months in rural Ethiopia.
AB - The causes of acute malnutrition-or "wasting"-are complex, and a better
understanding of the underlying drivers is necessary in order to design effective
interventions. Water, sanitation, and hygiene (WASH) practices may play a
fundamental role in acute malnutrition, but more research is needed to confirm
this relationship. We investigated the association between WASH practices and
acute malnutrition among children 6 to 59 months of age in rural Ethiopia, making
use of the Ethiopian Demographic and Health Survey. Descriptive statistics were
used to assess the WASH status of all rural children. Bivariate logistic
regression analyses were performed to assess associations between nutritional
status and WASH. Multivariate logistic regression analyses were used to adjust
for confounders. A total of 7,209 children were included in the analysis, of
which 867 (12.0%) were acutely malnourished. Proper toilet facilities (AOR =
0.63, 95% CI [0.46, 0.86]) and a water source close to home (AOR = 0.71, 95% CI
[0.61, 0.83]) were associated with a lower prevalence of wasting. A safe water
source for drinking (COR = 1.03, 95% CI [0.89, 1.19]) and a safe disposal of the
child's stool (AOR = 0.97, 95% CI [0.84, 1.13]) were not significantly associated
with acute malnutrition. These results suggest that WASH practices are related to
acute malnutrition. Future studies-in particular intervention studies-should
investigate whether improving WASH practices is effective in reducing
malnutrition in infants and young children.
PMID- 29961979
TI - Impact of the Acid Treatment on Lignocellulosic Biomass Hard Carbon for Sodium
Ion Battery Anodes.
AB - The investigation of phosphoric acid treatment on the performance of hard carbon
from a typical lignocellulosic biomass waste (peanut shell) is herein reported. A
strong correlation is discovered between the treatment time and the structural
properties and electrochemical performance in sodium-ion batteries. Indeed, a
prolonged acid treatment enables the use of lower temperatures, that is, lower
energy consumption, for the carbonization step as well as improved high-rate
performance (122 mAh g-1 at 10 C).
PMID- 29961980
TI - Alkali Metal Species in the Reversible Activation of H2.
AB - MP(tBu)2 (M=Li, Na, K), KH and KN(SiMe3 )2 are shown to activate HD reversibly.
In the case of MP(tBu)2 this leads to isotopic scrambling and the formation of H2
, D2 , H(D)P(tBu)2 and MH(D) in C6 D6 . In toluene, KP(tBu)2 reacts with H2 but
also leads to isotopic scrambling into the methyl groups of the solvent toluene.
DFT calculations reveal that these systems effect H2 activation via cooperative
interactions with the Lewis acidic alkali metal and the basic phosphorus,
carbanion, or hydride centres, mimicking frustrated Lewis pair (FLP) behaviour.
PMID- 29961981
TI - GFR-related risks for kidney donors are here to stay, but what are they?
PMID- 29961982
TI - Quantitative path to deep phenotyping: Possible importance of reduced hepatic
insulin degradation to type 2 diabetes mellitus pathogenesis.
PMID- 29961983
TI - Dietary sodium intake and its relationship to adiposity in young black and white
adults: The African-PREDICT study.
AB - Obesity and salt intake are both established factors contributing to
cardiovascular disease development. Recently, studies found a controversial
positive relationship between dietary salt and obesity. Therefore, the authors
investigated whether obesity-related measures are associated with 24-hour urinary
sodium in a healthy biethnic population. The study included 761 adults (20-30
years) with complete 24-hour urinary sodium, anthropometry, and bioelectrical
impedance measurements. In single regression analyses all obesity-related
measures related positively with 24-hour urinary sodium (P <= .008). However,
with multivariate adjustments for energy intake, accelerometery, age, sex, black
and white ethnicity, and other covariates, only body surface area (BSA) remained
independently associated with 24-hour urinary sodium (R2 = 0.72, beta = .05, P =
.039). To conclude, we found a consistent and robust positive relationship
between BSA and estimated salt intake - but not with traditional obesity measures
such as body mass index (BMI). Further studies are needed to investigate body
surface area and potentially, skin area, in salt handling.
PMID- 29961984
TI - Structural basis for species-specific activation of mouse Toll-like receptor 9.
AB - Single-stranded DNA containing unmethylated cytosine-phosphate-guanine (CpG)
motifs derived from microorganisms are recognized by Toll-like receptor (TLR) 9
and activate an innate immune response. TLR9 has two DNA-binding sites for CpG
DNA and DNA containing cytosine at the second position from the 5'-end; both are
required for efficient TLR9 activation in most vertebrate species. However, mouse
TLR9 can be dimerized by CpG DNA only, although the underlying mechanism remains
elusive. Here, we report the crystal structure of mouse TLR9 complexed with both
DNAs. Although most TLR9-CpG DNA interactions are conserved among species, some
are unique to mice and involved in species-specificity. These findings provide
the structural basis for how mouse TLR9 dimerizes efficiently in response to CpG
DNA to activate innate immunity.
PMID- 29961985
TI - Lipid oxidation stability of ultra-high-temperature short-time sterilization
sporoderm-broken pine pollen (UHT-PP) and 60 Co-irradiation sterilization
sporoderm-broken pine pollen (60 Co-PP).
AB - BACKGROUND: Pine pollen, a kind of Chinese traditional medicine, is rich in
unsaturated fatty acids. During its processing, it is often needed to break the
sporoderm in order to increase the availability of some ingredients, which can
cause lipid oxidation and the development of rancidity during storage. RESULTS:
The primal peroxide value (PV) of ultra-high-temperature short-time sterilization
sporoderm-broken pine pollen (UHT-PP) was much higher (over 15 times) than raw
pine pollen (R-PP) and 60 Co-irradiation sterilization sporoderm-broken pine
pollen (60 Co-PP). The PV of UHT-PP first increased and then decreased shortly
after; however, PV of R-PP and 60 Co-PP remained almost unchanged during storage.
The volatiles associated with rancidity in UHT-PP were found to be significantly
higher than 60 Co-PP, especially hexanal (nearly 30 times) and hexanoic acid
(about 2 times), and a multi-organoleptic sensor analyzer (electronic nose
system) was able to differentiate these three kinds of samples when the output
was subjected to discriminant function analysis. During storage (30 days),
hexanal first increased and then decreased (at about 5 days), and hexanoic acid
continuously increased for UHT-PP; however, no significant change was noted for R
PP or 60 Co-PP. UHT-PP has a greater surface area than 60 Co-PP, although same
sporoderm-broken processes were applied. Antioxidants (flavone, carotenoid and
tocopherols, sterol compounds) in 60 Co-PP were significantly (P <= 0.05, by
Duncan's multiple range test) higher than that in UHT-PP, although not
significantly different for total phenolics. CONCLUSIONS: Rancidity occurs more
readily in UHT-PP than in R-PP and 60 Co-PP during storage, probably because
significant lipid oxidation and antioxidant degradation occurred during the UHT
sterilization sporoderm-broken processing of pine pollen. (c) 2018 Society of
Chemical Industry.
PMID- 29961986
TI - The Effect of CAD/CAM Crown Material and Cement Type on Retention to Implant
Abutments.
AB - PURPOSE: To evaluate the pullout resistance of CAD/CAM implant-supported crowns
cemented with provisional and definitive cements on Ti-base implant abutments.
MATERIALS AND METHODS: Sixty crowns were milled for use in Ti-base implant
abutments and divided (n = 15/group) according to material, as follows: (a) [Pr]
Temporary acrylic resin; (b) [Co-Cr] Cobalt-Chromium alloy; (c) [Zr]
polycrystalline zirconia; and (d) [Ti] titanium. The cementation was performed
with RelyX Temp NE (RxT) cement or RelyX U200 self-etching resin cement, under a
50 N (5 kg) load for 10 minutes. Twenty-four hours after cementation, the crowns
were subjected to the pullout test in a universal test machine, at a 1.0 mm/min
crosshead speed. The tests were performed first without cement to evaluate
frictional resistance (Baseline), then with provisional cement (RelyX Temp NE
without cement again (Baseline After RxT), and finally with resin cement (U200).
The results were analyzed by ANOVA and Tukey test (p < 0.05). RESULTS: Data
evaluation as a function of cement type demonstrated the superiority of resin
based cements relative to provisional and baseline groups (p < 0.01). While Co-Cr
crowns presented the highest pullout strength values, Pr showed the lowest values
(data collapsed over cement) (p < 0.001). Retentiveness data as a function of
both factors demonstrated similar pullout resistance between groups without
cement (p < 0.001), except Zr baseline. Also, Co-Cr presented higher pullout
strength compared to other materials. CONCLUSIONS: Self-adhesive resin cement
exhibited superior retention compared to temporary cement, regardless of crown
material. Co-Cr and titanium presented higher levels of retention to Ti-base
abutment after being cemented.
PMID- 29961987
TI - Extraction and determination of heavy metals in soil and vegetables irrigated
with treated municipal wastewater using new mode of dispersive liquid-liquid
microextraction based on the solidified deep eutectic solvent followed by GFAAS.
AB - BACKGROUND: In this research, a new extraction method based on dispersive liquid
liquid microextraction and the solidification of deep eutectic solvent has been
developed for the determination of heavy metals in soil and vegetables prior to
their analysis by graphite furnace atomic absorption spectrometry (GFAAS). In
this method, a green solvent consisting of 1-decyl-3-methylimidazolium chloride
and 1-undecanol was used as an extraction solvent, yielding the advantages of
material stability, low density and a suitable freezing point near room
temperature. RESULTS: Under optimal conditions, enrichment factors are in the
range of 114-172. The calibration graphs are linear in the range of 0.02-200 ug
kg-1 and limits of detection are in the range of 0.01-0.03 ug kg-1 .
Repeatability and reproducibility of the method based on seven replicate
measurements of 0.80 ug kg-1 of Hg and 0.20 ug kg-1 of Pb and Cd in analyzed
samples were in the range of 2.3-4.1% and 3.7-6.6%, respectively. CONCLUSION: A
new deep eutectic solvent consists of two parts: 1-decyl-3-methylimidazolium
chloride and 1-undecanol in a molar ratio of 1:2. The accuracy of the proposed
procedure was also assessed by determining the concentration of the studied metal
ions in a polluted farmland soil standard reference material. (c) 2018 Society of
Chemical Industry.
PMID- 29961988
TI - Prevalence, extent and severity of peri-implant diseases. A cross-sectional study
based on a university setting in Brazil.
AB - BACKGROUND AND OBJECTIVE: Peri-implant diseases are a growing concern among
clinicians. Epidemiological studies following recently recommended case
definitions for peri-implant diseases are emerging worldwide. Although a small
number of studies on the prevalence of peri-implant diseases has been conducted
in Brazil, no information on the extent and severity of the condition has been
made available so far. The objective of this study was to estimate the
prevalence, extent and severity of peri-implant diseases in patients treated in a
university setting in Brazil. MATERIAL AND METHODS: Patients with dental implants
with at least 1 year in function were clinically and radiographically examined
and classified according to recently recommended case definitions. A descriptive
analysis on the prevalence, extent and severity of the peri-implant status at
patient and implant level was performed. Risk indicators for peri-implantitis
were also identified with binary logistic regression analysis. RESULTS: Of the
211 participating individuals, 4 (1.9%) presented peri-implant health, 8 (3.8%)
clinical stability, 115 (54.5%) mucositis and 84 (39.8%) peri-implantitis. Of the
748 implants analyzed, 47 (6.3%) presented peri-implant health, 30 (4%) clinical
stability, 518 (69.2%) mucositis and 153 (20.5%) peri-implantitis. The extent of
implants with peri-implantitis and peri-implant mucositis was 41.5% and 90.4%,
respectively. Severe peri-implantitis was found in 36 patients (17.1%) and 67
implants (9%). Gender male, number of implants >=4, implants installed in the
maxilla, cemented prosthesis and keratinized mucosa width <2 mm were
significantly associated with the event peri-implantitis. CONCLUSION: In the
studied population, the prevalence, extent and severity of the peri-implant
diseases were similar to those reported elsewhere. Peri-implant diseases were a
common finding, with only 5.7% of patients and 10.3% of implants presenting peri
implant health or clinical stability. About 17% of patients studied presented the
severe form of peri-implantitis.
PMID- 29961989
TI - Focal cortical cataract due to caterpillar hair migration.
PMID- 29961990
TI - Feline pemphigus foliaceus in non-specialist veterinary practice: a retrospective
analysis.
AB - OBJECTIVES: To characterise the signalment, clinical presentation and therapy of
pemphigus foliaceus in cats treated by primary care practitioners. MATERIALS AND
METHODS: Retrospective evaluation of patient and treatment factors with the
following case outcomes: remission (achieving remission, time to remission),
treatment-related adverse effects (number, severity) and final disease outcome
(medical control, cure, death or euthanasia). RESULTS: Data were obtained from 48
cats with biopsy-confirmed pemphigus foliaceus managed by practitioners from six
countries and 47 hospitals. Clinicians prescribed oral prednisolone most commonly
for immunosuppression (median dose 2.2 mg/kg/day). Disease remission information
was available in 40 cats; 90% achieved disease remission, which did not appear
related to the doses of oral glucocorticoid administered in this study. Disease
relapse occurred in 29 (73%) cats after achieving remission, necessitating
medication adjustments. Severe treatment-related adverse effects occurred in
eight cases, including both cats treated with long-acting injectable
glucocorticoids. Of 31 cats treated with glucocorticoid monotherapy, 27 achieved
remission, as did eight of 11 ciclosporin plus glucocorticoid-treated cats.
Eleven cats experienced adverse effects: five receiving ciclosporin plus
glucocorticoid and six receiving glucocorticoid monotherapy. CLINICAL
SIGNIFICANCE: Pemphigus foliaceus remission with treatment is highly likely in
cats but relapse is common, necessitating close monitoring and individualised
therapy modifications. Clinicians should focus on the judicious use of
glucocorticoids to minimise treatment-related adverse effects, such as avoiding
injectable glucocorticoids, combining glucocorticoids with steroid-sparing
medications, and regularly rechecking patients to adjust drug dosages in response
to disease status.
PMID- 29961991
TI - Hyperplastic sensory corpuscles in nevus sebaceus of labia minora pudendi. A case
report.
AB - A vulvar case of nevus sebaceus is presented. During the routine histopatological
examination, attention was drawn by several corpuscular structures.
Immunohistochemistry demonstrated that they were sensory corpuscles, identified
respectively as Meissner-like and glomerular corpuscles. Nevertheless, compared
with typical Meissner corpuscles from digital glabrous skin, Meissner-like
corpuscles identified here were bigger, the axon showed an irregular course, and
the lamellar cells were smaller. Regarding the glomerular corpuscles they were
bigger but with a normal arrangement of the corpuscular constituents. These
findings suggest that these cutaneous sensory corpuscles are part of the nevus
sebaceus hamartoma.
PMID- 29961992
TI - When I say ... understand.
PMID- 29961993
TI - Frequency of circulating CD14++ CD16+ intermediate monocytes as potential
biomarker for the diagnosis of oral squamous cell carcinoma.
AB - BACKGROUND: Monocytes, which subdivided into three functional subsets (classical,
intermediate, and nonclassical), play important roles in the progression of
cancer. The subset composition is altered in several pathologic conditions
including cancers. However, the composition and function of circulating monocyte
subsets in patients with oral squamous cell carcinoma (OSCC) are still obscure.
METHODS: The frequencies of monocyte subsets in peripheral blood of patients with
OSCC and healthy donors are determined by flow cytometry, and their diagnostic
values for OSCC were evaluated. The associations between levels of monocyte
subsets and clinicopathological features of patients with OSCC were analyzed
using cross-tabulation with the chi-square test. RESULTS: We demonstrated that
the frequency of CD14++ CD16+ intermediate monocytes was remarkably increased (P
< 0.0001) in OSCC patients compared with healthy controls (7.33% +/- 2.56% of
total monocytes, n = 68 versus 4.78% +/- 1.50% of total monocytes, n = 57). A
trend of decrease in CD14++ CD16- classical subset was observed between these two
groups (P = 0.0508), whereas no significant difference was detected in CD14+
CD16++ nonclassical subset (P > 0.05). The receiver operating characteristic
(ROC) curve analysis indicated that the frequency of intermediate monocytes (AUC
= 0.810, P < 0.0001) could be a potential diagnostic biomarker to discriminate
patients with OSCC from healthy subjects. Moreover, this parameter was
significantly correlated to the worst pattern of invasion (WPOI, P < 0.05) of
OSCC tissues. CONCLUSIONS: Detection of monocyte subsets in peripheral blood
sheds a light on utilizing the frequency of intermediate monocytes as a potential
diagnostic biomarker for OSCC.
PMID- 29961994
TI - In vivo biocompatibility and biomineralization of calcium silicate cements.
AB - A new mineral trioxide aggregate (MTA) material has been developed with a
modified composition that requires investigations to support its clinical use.
This study evaluated the biocompatibility and biomineralization of this new MTA
material and compared it with that of two other MTA cements over time. Tubes
containing materials (or empty tubes as controls) were inserted into the
subcutaneous tissues of 40 rats. On days 7, 15, 30, 60, and 90, the tubes were
removed with the surrounding tissues, which were either stained with haematoxylin
and eosin or von Kossa for further analyses or unstained for observation under
polarized light. On days 7 and 15, moderate inflammation was observed in most
specimens, and the fibrous capsule was thick. On day 30, there was mild
inflammation in all groups, and the fibrous capsule was thin. On days 60 and 90,
there was mild inflammation in the material groups, while the control group
showed no inflammation, although no statistically significant difference between
the groups was observed and the fibrous capsule was thin. All material groups
showed structures that stained with von Kossa and could be observed under
polarized light; this was not found for the control. In conclusion, the new MTA
material had biocompatibility and biomineralization properties similar to those
of the two existing MTA materials.
PMID- 29961995
TI - In search of cerebrospinal fluid biomarkers of fatigue in multiple sclerosis: A
proteomics study.
AB - Fatigue in multiple sclerosis is a very common and cumbersome symptom, but its
aetiology is poorly understood. Proteomics is increasingly implemented in
multiple sclerosis research, but has not yet been used to study the
neurobiological basis of fatigue in multiple sclerosis. To identify potential
cerebrospinal fluid biomarkers of fatigue in multiple sclerosis, we collected
cerebrospinal fluid of 20 patients with multiple sclerosis with fatigue (MS+), 20
patients with multiple sclerosis without fatigue (MS-), and 20 control subjects
without multiple sclerosis and without fatigue (HC). We used a shotgun proteomics
approach and label-free quantitative proteomics to analyse the protein content in
cerebrospinal fluid. Selected proteins with differential abundance were further
validated by immunoblotting. Out of 591 detected cerebrospinal fluid proteins,
the abundance of nine proteins differed between the three groups, and seven
additional proteins differed between MS+ and MS- patients. Using immunoblot or
slot-blot techniques, we confirmed decreased levels of protein kinase C-binding
protein NELL2, neural cell adhesion molecule L1-like protein, and reelin in MS+
patients. In conclusion, cerebrospinal fluid proteomics may provide insight into
the neurobiological basis of fatigue in multiple sclerosis. The proteins
identified to be decreased in MS+ are involved in synaptic plasticity and energy
homeostasis, and thus appear as plausible biomarkers of this common symptom.
PMID- 29961996
TI - Substance use disorders in patients with intellectual disability admitted to
psychiatric hospitalisation.
AB - BACKGROUND: Few studies have looked at the prevalence of substance use disorders
(SUD) in people with intellectual disability (ID). The results range between 1%
and 6.4% and go up to 20% in people with ID and psychiatric disorders, probably
underestimating real prevalence due to several limitations in these studies. ID
confers risk for the development of SUD, which in turn will involve negative
psychosocial and clinical consequences. We aimed to study the prevalence of SUD
in a sample of patients with ID admitted to a brief hospitalisation psychiatric
unit, describing them by type and severity and analysing their relationship with
clinical, prognostic and access to treatment variables. METHODS: We undertook a
descriptive, cross-sectional and retrospective study by means of a review of
clinical histories of all patients with a diagnosis of ID, admitted in a period
of 10 years. RESULTS: Among the final sample of patients included, 52.3% had a
mild ID, 40.9% an unspecified ID, 3.4% a moderate ID and another 3.4% a severe
ID. More than one third of the sample met criteria for a SUD. The main SUD was
cannabis use disorder (25%), followed by alcohol use disorder (22.7%) and cocaine
use disorder (13.6%). The use of more than one substance was the most frequent
pattern. Cannabis use disorder and cocaine use disorder were overrepresented in
the group with mild ID. A greater number of psychiatric admissions was observed
for the group with SUD. Specialised mental health services for ID and specialised
addiction network facilities were much less involved in the care of these
patients that could be expected according to good clinical practice
recommendations. CONCLUSIONS: Substance use disorder in patients with ID and
mental health disorders admitted to psychiatric hospitalisation are prevalent,
which makes this issue an area of interest for future improvements in case
identification, proper referring to specialised treatment resources and an
increasing research focusing on specific therapeutic approaches.
PMID- 29961997
TI - Development and applicability of a tool for identification of people with
intellectual disabilities in need of palliative care (PALLI).
AB - BACKGROUND: Timely identifying people with intellectual disabilities in need of
palliative care is important. Therefore, we developed PALLI: a screening tool for
deteriorating health, indicative of a limited life expectancy. Here, we aimed to
describe development of PALLI and to explore its applicability. METHOD: We used a
five-stage mixed-methods procedure to develop PALLI based on knowledge from
practice. For exploring applicability, professionals caring for people with
intellectual disabilities completed PALLI for 185 people with intellectual
disabilities and provided information on applicability after 5-6 months. RESULTS:
The final version of PALLI included 39 questions relevant for people with
intellectual disabilities. Applicability was adequate: Most professionals found
PALLI relevant and reported no ambiguous questions. Added value of PALLI was
reflecting on and becoming aware of the process of decline in health.
CONCLUSIONS: PALLI shows promising applicability and has potential as a tool for
timely identifying people with intellectual disabilities who may benefit from
palliative care.
PMID- 29961998
TI - Empagliflozin compared with glimepiride in metformin-treated patients with type 2
diabetes: 208-week data from a masked randomized controlled trial.
AB - AIM: To report results at week 208, including a 104-week masked extension, of the
EMPA-REG H2H-SU trial in patients with type 2 diabetes with inadequate glycaemic
control on metformin, in which empagliflozin 25 mg given for 104 weeks provided a
sustained reduction in glycated haemoglobin (HbA1c) with a small but
statistically significant benefit vs glimepiride, sustained reductions in weight
and blood pressure, and low risk of hypoglycaemia. RESEARCH DESIGN AND METHODS:
Patients with type 2 diabetes and HbA1c 53-86 mmol/mol (7% to 10%) were
randomized to empagliflozin 25 mg or glimepiride 1 to 4 mg for 104 weeks as add
on to metformin. Patients who completed the randomized treatment period could
participate in a 104-week extension in which they continued the double-blind
treatment allocated at randomization. RESULTS: Of 765 and 780 patients treated
with empagliflozin and glimepiride, 576 and 549 patients, respectively, entered
the extension period of the study. At week 208, the adjusted mean difference in
change from baseline in HbA1c with empagliflozin vs glimepiride was -1.96
mmol/mol, 95% CI -3.57, -0.35 (-0.18%, 95% CI -0.33, -0.03); P = 0.0172. Rescue
therapy was given to 23% of patients on empagliflozin and 34% on glimepiride
(odds ratio 0.56 [95% CI 0.45, 0.71]; P < 0.0001). Confirmed hypoglycaemic
adverse events (plasma glucose <=3.9 mmol/L and/or requiring assistance) occurred
in 3% of patients on empagliflozin and 28% on glimepiride (odds ratio 0.08 [95%
CI 0.05, 0.13]; P < 0.0001). CONCLUSIONS: In patients with type 2 diabetes,
empagliflozin 25 mg as add-on to metformin for 208 weeks reduced HbA1c with a
significantly lower risk of hypoglycaemia and a significantly smaller proportion
of patients receiving rescue therapy compared with glimepiride.
PMID- 29961999
TI - Associations of left atrial volumes and Doppler filling indices with left atrial
function in acute myocardial infarction.
AB - Recent findings suggest that left atrial (LA) function is more strongly related
to adverse prognosis than LA volumes. We aimed to evaluate the associations
between LA volumes and Doppler filling indices with LA function.
Echocardiographic LA volumes (LAVs), mitral valve early (MV-E) and late (MV-A)
peak flow velocities, and mitral atrioventricular plane tissue-Doppler early (TD
e') and late (TD-a') peak velocities were obtained in 320 patients with acute
myocardial infarction (AMI) free from atrial fibrillation and more than moderate
valvular disease. LA function was estimated as the LA emptying fraction (LAEF),
that is 100* (LAVmax-LAVmin)/LAVmax. LA reservoir volume was calculated as LAVmax
LAVmin and LA transit volume as LV stroke volume-reservoir volume. In restricted
cubic spline regression analyses with multivariable adjustment, a reduced LAEF
was strongly associated with smaller reservoir volume, larger transit volume,
LAVmax, LAVpreA and especially LAVmin. MV-E linearly increased with a lower LAEF,
whereas MV-A decreased but only below LAEF levels of approximately 45%. The
resulting E/A ratio showed a sudden increase in LAEF levels below ~45%. Lower TD
a' was linearly associated with a lower LAEF. In conclusion, a reduced atrial
function was associated with smaller LA reservoir volume, larger LA transit
volume, lower TD-a', a non-linear decrease in MV-A and a non-linear increase in
E/A. Our findings are likely a reflection of the adaptation to sustain LV filling
volume and counteracting a rise in pulmonary venous pressure in face of an
enhanced LV end-diastolic pressure.
PMID- 29962000
TI - The seven habits of highly effective clinical support time.
PMID- 29962001
TI - Preferential incorporation of dark, coloured materials into nests by a mound
nesting stream cyprinid.
AB - We compared size and colour characteristics of rocks used by male cutlip minnows
Exoglossum maxillingua to build nests to those of streambed background materials.
We found that materials used to construct conspicuous, mound-shaped nests were
uniform in size and darker and more colour-saturated than background materials of
the same size. To our knowledge, this phenomenon is the first reported example of
fish selecting nest materials based on colour and has important implications for
the conservation of mound-nesting stream cyprinid species.
PMID- 29962002
TI - HPLC-MS/MS combined with membrane-protected molecularly imprinted polymer micro
solid-phase extraction for synthetic cathinones monitoring in urine.
AB - Synthetic cathinones are a type of drug belonging to group of new psychoactive
substances (NPSs). The illicit market for these substances is characterized by
the continuous introduction to the market of new analogs to evade legislation and
to avoid detection. New screening and confirmation assays are therefore needed,
mainly in forensic/clinical samples. In the current development, a porous
membrane-protected, micro-solid-phase extraction (MU-SPE) has been developed for
the assessment of several cathinones in urine. The MU-SPE device consisted of a
cone-shaped polypropylene (PP) porous membrane containing the adsorbent
(molecularly imprinted polymers, MIPs, synthesized for the first time for this
class of drugs). MIPs were prepared using ethylone and 3-methylmethcathinone (3
MMC) as templates, ethylene glycol dimethacrylate (EGDMA) as a functional
monomer, divinylbenzene (DVB) as a cross-linker, and 2,2'-azobisisobutyronitrile
(AIBN) as an initiator. The prepared ethylone-based MIP and 3-MMC-based MIP have
been fully characterized and evaluated as new selective adsorbents for MU-SPE.
Cathinones separation/determination was performed by high performance liquid
chromatography-tandem mass spectrometry (HPLC-MS/MS). Optimum loading conditions
(pH 5.0, loading for 4.0 minutes under orbital-horizontal shaking at 200 rpm) and
elution conditions [2.0 mL of 75:20:5 heptane/2-propanol/ammonium hydroxide and
ultrasounds assistance (37 kHz, 325 W) for 4.0 minutes] were found for ethylone
based MIP. Validation (intra-day and inter-day precision and analytical recovery)
showed RSD values lower than 9 and 10% for intra-day and inter-day precision, and
within the 88%-101% range for intra-day and inter-day analytical recovery.
PMID- 29962003
TI - Nimbolide induced apoptosis by activating ERK-mediated inhibition of c-IAP1
expression in human hepatocellular carcinoma cells.
AB - Nimbolide is one of the major compounds from the leaves and flowers of the neem
tree and exhibits antitumor properties on various cancer cells. However, no
report has shown that nimbolide induces apoptosis in vitro and in vivo in human
hepatocellular carcinoma cells. Our results indicated that it inhibited cell
growth in Huh-7 and PLC/PRF/5 cells. We also found that nimbolide induced cell
death through the induction of G2/M phase arrest and mitochondrial dysfunction,
accompanied by the increased expression of cleaved caspase-7, caspase-9, caspase
3, caspase-PARP, and Bax and decreased expression of Mcl-1 and Bcl-2. A human
apoptosis antibody array analysis demonstrated that inhibition of the apoptosis
family proteins (XIAP, c-IAP1, and c-IAP2) was one of the major targets of
nimbolide. Additionally, nimbolide sustained activation of ERK expression.
Moreover, pretreatment with U0126 (MEK inhibitor) markedly abolished nimbolide
inhibited cell viability, induced cell apoptosis, ERK phosphorylation, cleaved
caspase-9, caspase-3, cleaved-PARP activation, and increased c-IAP1 expression in
Huh-7 cells. An in vivo study showed that nimbolide significantly reduced Huh-7
tumor growth and weight in a xenograft mouse model. This study indicated the
antitumor potential of nimbolide in human hepatocellular carcinoma cells.
PMID- 29962004
TI - p63 and smooth muscle actin expression in low-grade spiradenocarcinomas in a case
of CYLD cutaneous syndrome.
AB - Low-grade spiradenocarcinoma is a rare skin tumor, with fewer than six reported
cases, arising in the context of CYLD cutaneous syndrome (CCS; syn: Brooke
Spiegler syndrome [BSS]). We report two independent cases of spiradenocarcinoma
arising in a 50-year-old man with CCS. The tumors grew rapidly, prompting
clinical excision. The histologic features in our cases corresponded to the
salivary gland type basal cell adenocarcinoma-like pattern, low grade (BCAC-LG),
that has been previously recognized as a recurrent finding in CCS. We performed
genetic testing of the patient and found a novel mutation in CYLD. Recognition of
low-grade spiradenocarcinoma can be difficult for the pathologist as the features
can be subtle, especially in those cases where the transition from benign to
malignant tumor is gradual. We examined p63 and smooth muscle actin (SMA)
expression patterns in BCAC-LG and compared it with the expression pattern in the
precursor spiradenoma. Our report provides information on two rare tumors in the
context of CCS and suggests that the pattern of p63 and SMA staining may aid
pathological detection of the BCAC-LG subtype of spiradenocarcinoma.
PMID- 29962005
TI - A retrospective analysis of surgical resection of large ear keloids.
AB - OBJECTIVE: To investigate surgical methods for the removal of larger ear keloids.
METHODS: Two different surgical techniques were used: Method A, tumour excision
followed by in situ scar flap repair; and Method B, wedge resection of an
auricular lesion followed by primary closure or local flap repair. After the
treatment, patients received postoperative, local radiotherapy. Follow-up was for
1-3 years (median 28.9 months). RESULTS: Twenty patients with 35 large ear
keloids were reviewed. In Method A, six ears were cured, three ears improved,
five ears relapsed after 1 year and one ear recurred within 1 year. In Method B,
17 ears were cured, two ears improved and one ear recurred within 1 year.
CONCLUSION: Keloid scars can be effectively treated with a combination of
radiotherapy and surgical excision.
PMID- 29962007
TI - July 2018 at a glance: practical guidance in acute heart failure, pathophysiology
and clinical trials of medical therapy.
PMID- 29962008
TI - Faecal calprotectin delivers on convenience, cost reduction and clinical decision
making in inflammatory bowel disease: a real world cohort study.
AB - BACKGROUND: Faecal calprotectin (FC) is an accurate biomarker of disease activity
in inflammatory bowel disease (IBD), yet the cost/resource implications of
incorporating FC into 'real world' practice remain uncertain. AIM: To evaluate
the utility of FC in clinical decision-making and on healthcare costs in IBD.
METHODS: Retrospective data including colonoscopy/ other investigations,
medication, admission and surgical data were collected from hospital records and
compared between two groups: (1) pre-FC historical cohort (2005-09) where
colonoscopy was used to assess IBD activity versus (2) FC was used first instead
(2010-14). Post-test costs were also compared. RESULTS: 357 FC tests (246
patients, 2010-14) and 450 colonoscopies (268 patients, 2005-9) were performed.
At subsequent review, both FC and colonoscopy (in their respective cohorts) were
associated with changes in management in 50.7 vs 56.2% respectively (p=0.14) with
similar proportions of subsequent IBD-related investigations within 6 months
(21.8 vs 21.9%, p=1.0). Prior FC availability (2005-09), colonoscopy for disease
reassessment cost $AUD606,578 (cost per patient-year $1887.34) versus $AUD282,048
(cost per patient-year $968.60) when FC+/-colonoscopy was used (2010-2014).
Within the FC cohort, 73.6% did not proceed to colonoscopy within 6 months post
FC, 60.6% had not undergone colonoscopy post-FC by end of follow-up (median 1.8y
(0.1,4.6) post-FC). Those with FC>=250 were scoped earlier than those with FC<100
MUg/ml (median 0.49 vs 1.0 years, p=0.03). CONCLUSIONS: Introduction of FC into
routine IBD care aided changes in clinical management in a similar proportion,
yet at potentially half the total cost, compared to a historical colonoscopy-only
cohort at the same centre. This article is protected by copyright. All rights
reserved.
PMID- 29962006
TI - Implants induce a new niche for microbiomes.
AB - Although much work is being done to develop new treatments, research and
knowledge regarding factors underlying implant-related microbial colonization
leading to infection are less comprehensive. Presence of microorganisms in and
around implants clinically characterized as uninfected remains unknown. The
objective of this study was to detect and identify bacteria and fungi on implants
from various groups of patients with no prior indications of implant related
infections. Patient samples (implants and tissue) were collected from five
different hospitals in the Capital region of Denmark. By in-depth microbiological
detection methods, we examined the prevalence of bacteria and fungi on 106
clinically uninfected implants from four patient groups (aseptic loosening,
healed fractures, craniofacial complications and recently deceased). Of 106
clinically uninfected implants and 39 negative controls investigated, 66% were
colonized by bacteria and 40% were colonized by fungi (p < 0.0001 compared to
negative controls). A large number of microbes were found to colonize the
implants, however, the most prevalent microbes present were not common
aetiological agents of implant infections. The findings indicate that implants
provide a distinct niche for microbial colonization. These data have broad
implications for medical implant recipients, as well as for supporting the idea
that the presence of foreign objects in the body alters the human microbiome by
providing new colonization niches.
PMID- 29962009
TI - Beyond competencies - describing work ready plus graduates for the New Zealand
medical imaging workforce.
AB - INTRODUCTION: Medical imaging is a profession where technology and practice is
moving forward at a fast pace, while also being situated within rapidly evolving
models of healthcare delivery. This requires capabilities in our graduates beyond
the competencies to undertake the role. This study used an existing Professional
Capability Framework as the foundation for the development of a survey tool to
identify those capabilities most valued by the health services that provide
placement opportunities for students. METHODS: A prospective survey, conducted
online, was used to gather the data from senior medical imaging staff who work
regularly with students and new graduates. RESULTS: The results identified the
top capabilities within each of three domains of personal, interpersonal, and
cognitive capabilities. The results from the personal domain show that remaining
calm under pressure or when things take an unexpected turn; understanding
personal strengths and limitations; being willing to face and learn from errors;
wanting to do as good a job as possible and having energy, passion and enthusiasm
for the profession and role are most valued by the profession. We have identified
links between the most desired interpersonal capabilities and attributes of well
functioning interprofessional teams and the cognitive capabilities align to those
required for critical thinking and clinical reasoning. CONCLUSIONS: These results
have allowed the curriculum development team to review the graduate profile of
medical imaging technology graduates. The curriculum development team has begun a
process to incorporate learning strategies that will encourage the development of
these capabilities in our graduates.
PMID- 29962010
TI - Compassion fatigue in nursing: A concept analysis.
AB - AIM: The aim of this article is to clarify the concept of compassion fatigue to
develop methods for prevention and mitigation of compassion fatigue in the
nursing profession. BACKGROUND: Compassion fatigue occurs when nurses develop
declining empathetic ability from repeated exposure to others' suffering.
Conceptual clarity is vital to curtail compassion fatigue via preventative and
restorative measures at the individual and organizational level. DESIGN: Concept
analysis. DATA SOURCES: Databases searched were OVID, CINAHL Complete, Science
Direct, Academic One File, Criminal Justice Abstracts, Education Full Text (H.W.
Wilson), PsycARTICLES, PsycINFO, Social Work Abstracts, and Teacher Reference
Center. Keywords included concept analysis, compassion fatigue, secondary
traumatic stress, burnout, vicarious traumatization, compassion satisfaction,
nursing, psychology, and social work. The timeline for data collection was from
1990 to 2017. METHODS: Walker and Avant's method of concept analysis. RESULTS:
Compassion fatigue occurred across disciplines. Nurses were predisposed to
compassion fatigue by repeated exposure of others' suffering, high stress
environments, and the continuous giving of self. The consequences of compassion
fatigue negatively impacted the nurse, patient, organization, and healthcare
system. CONCLUSION: All nurses are at risk for compassion fatigue. Prevention of
compassion fatigue is achieved through professional boundaries, self-care
measures, self-awareness, and education on the concept at the individual and
organizational level.
PMID- 29962011
TI - Certification of fitness to drive in sleep apnea patients: Are we doing the right
thing?
AB - New European Union (EU) regulations state that untreated moderate to severe
obstructive sleep apnea (OSA) coincident with excessive daytime sleepiness (EDS)
constitutes a medical disorder leading to unfitness to drive. However, fitness to
drive can be re-established by successful treatment of OSA and EDS. The aim of
the current study was to compare patients undergoing the certification process
with those of an unselected OSA patient cohort. The study compared consecutive
patients in the certification group (n = 132) with a representative group of OSA
patients with a current driving license and an Apnea Hypopnea Index (AHI) >= 15
n/h (n = 790). The adherence to positive airway pressure (PAP) therapy and the
change in EDS (Epworth Sleepiness Scale [ESS] score) with treatment were
analysed. Patient characteristics and severity of sleep apnea did not differ
significantly between groups (certification/reference group: BMI 30 +/- 5/31 +/-
5 kg/m2 , AHI 33 +/- 20/36 +/- 20 n/hr, ESS 12 +/- 6/11 +/- 5). However, the
certification group was oversampled with elderly drivers (70-85 years: 22% vs.
9%, p = 0.001). PAP compliance was higher in the certification group than in the
reference group (PAP use >= 4 hr/night in 96% vs. 53%, p = 0.001) and mean ESS
reduction was -8.0 (-8.9 - -7.1) versus -4.0 (-4.4 - -3.5), respectively (p <
0.001). Patients attending the fitness to drive evaluation reported almost
complete adherence to continuous positive airway pressure (CPAP) and elimination
of EDS symptoms. Besides possible baseline differences, this strong response may
be explained by factors such as a selection process of elderly patients, a self
rating component in the assessment of the treatment response and the threat of a
driving license suspension. Our data suggest that an improved certification
process with objective rather than subjective components, along with a reduced
selection bias, is warranted.
PMID- 29962012
TI - Hypertension and cardiovascular disease: Is a treatment strategy focused on high
risk sufficient?
PMID- 29962014
TI - Nucleation-Controlled Plasticity of Metallic Nanowires and Nanoparticles.
AB - Nanowires and nanoparticles are envisioned as important elements of future
technology and devices, owing to their unique mechanical properties. Metallic
nanowires and nanoparticles demonstrate outstanding size-dependent strength since
their deformation is dislocation nucleation-controlled. In this context, the
recent experimental and computational studies of nucleation-controlled plasticity
are reviewed. The underlying microstructural mechanisms that govern the strength
of nanowires and the origin of their stochastic nature are also discussed.
Nanoparticles, in which the stress state under compression is nonuniform, exhibit
a shape-dependent strength. Perspectives on improved methods to study nucleation
controlled plasticity are discussed, as well the insights gained for
microstructural-based design of mechanical properties at the nanoscale.
PMID- 29962013
TI - Balance exercise facilitates everyday life for people with multiple sclerosis: A
qualitative study.
AB - OBJECTIVES: The aim of this qualitative study was to describe the experience and
perceived effects on everyday life for people with multiple sclerosis after
participating in a balance exercise programme focusing on core stability, dual
tasking, and sensory strategies (the CoDuSe programme). METHODS: A qualitative
approach was chosen, using face-to-face interviews analysed with content
analysis. Twenty-seven people with multiple sclerosis (20 women, 7 men) who had
participated in the CoDuSe programme were included. All could walk 20 m with or
without walking aids but could not walk further than 200 m. The CoDuSe programme
was given twice weekly during a 7-week period. RESULTS: The analysis revealed
five categories. Learning to activate the core muscles described how the
participants gained knowledge of using their core muscles and transferred this
core muscle activation into everyday life activities. Improved bodily confidence
covered narratives of being more certain of the ability to control their bodies.
Easier and safer activities showed how they could now perform activities in
everyday life more safely and easily. Increased independence and participation
involved the participants' improved ability and self-confidence to execute
activities by themselves, as well as their increased participation in activities
in daily living. Experiences of the balance exercise programme revealed that they
found the programme novel and challenging. The overall theme was balance exercise
facilitates everyday life. CONCLUSION: Participating in the CoDuSe programme was
perceived to facilitate everyday life for people with multiple sclerosis. Taking
part in the balance exercise programme taught the participants how to activate
and use the core muscles, which increased their bodily confidence. Having
increased bodily confidence helped them to perform everyday life activities with
more ease and safety, which increased their independence and participation. The
participants described the CoDuSe programme as novel and challenging, yet
feasible.
PMID- 29962015
TI - Risk of coronary artery disease and stroke according to sex and presence of
diabetic nephropathy in type 1 diabetes.
AB - AIMS: To determine the effect of different stages of diabetic nephropathy (DN)
and sex on the excess and absolute morbidity of coronary artery disease (CAD) and
stroke in people with type 1 diabetes (T1D) in order to distinguish different
cardiovascular disease (CVD) risk profiles in people with T1D. MATERIALS AND
METHODS: The study included 4410 people with T1D from the Finnish Diabetic
Nephropathy Study (FinnDiane), divided by DN status, and a control population of
12 434 people without diabetes. CVD events were identified from the Finnish
nationwide health registries. Cumulative incidences for CAD and stroke were
calculated and standardized incidence ratios (SIRs) were estimated between
participants with T1D and the control group, stratified by DN status and sex.
RESULTS: There were 487 incident CADs and 290 strokes at the end of 2014 (median
follow-up 12.9 years). The cumulative incidence rates of CAD and stroke were
similar in men and women within different nephropathy groups. The SIR for CAD was
7.5 (95% confidence interval [CI] 6.9-8.2), 17.2 (95% CI 14.9-19.5) in women and
5.3 (95% CI 4.7-5.9) in men. The women-to-men ratio of SIR increased by
nephropathy group: 3.3, 3.7, 5.3 and 6.8 in the normo-, micro- and
macroalbuminuria and end-stage renal disease (ESRD) groups, respectively. The SIR
for stroke was 5.0 (95% CI 4.3-5.5), similar in men and women. The women-to-men
ratio of SIR for stroke was 0.8, 1.3, 1.6 and 1.7, in the normo-, micro- and
macroalbuminuria and ESRD groups, respectively. The SIR in participants with
normoalbuminuria and an estimated glomerular filtration rate >=90 mL/min/1.73 m2
was 3.5 (95% CI 2.5-4.5) for CAD and 1.6 (95% CI 1.0-2.3) for stroke.
CONCLUSIONS: Although the excess CVD risk is several-fold greater in women
compared to men, the absolute CVD risk in men and women was equal when
nephropathy was taken into account. Even participants with normoalbuminuria and
normal kidney function were found to have an excess CVD risk compared with the
control group without diabetes.
PMID- 29962016
TI - Differential electrophysiological properties of D1 and D2 spiny projection
neurons in the mouse nucleus accumbens core.
AB - The striatum consists of the dorsal (caudate/putamen) and the ventral (nucleus
accumbens) regions. The nucleus accumbens is further divided into a core and
shell. Both the dorsal and ventral striatum contain populations of spiny
projection neurons, which make up 95% of the neurons within the striatum. SPNs
are canonically categorized into those that express the D1-type dopamine receptor
(D1 SPNs) and those that express the D2-type dopamine receptor (D2 SPNs). D1 and
D2 SPNs differ with respect to both synaptic inputs and projection targets. In
the dorsal striatum, it is well established that these populations of SPNs differ
in terms of their electrophysiological and morphological properties. However,
there remains a gap in our knowledge of the electrophysiological properties of
SPNs in the nucleus accumbens core. To evaluate the differential properties of
these SPNs, we performed whole-cell recordings from D1 and D2 SPNs in BAC
transgenic mice in which D1 SPNs fluoresce red and D2 SPNs fluoresce green. The
two SPN subtypes did not differ in terms of their time constant, capacitance,
resting membrane potential, or tonic current. However, D2 SPNs displayed
heightened inhibitory postsynaptic current (IPSC) and miniature excitatory PSC
frequency as compared with D1 SPNs. Furthermore, D2 SPNs displayed decreased
rheobase, increased excitability as measured by firing rates to depolarizing
current injections, increased inward rectification, increased input resistance,
and decreased dendritic complexity compared to D1 SPNs. Our results demonstrate a
dichotomy in the electrophysiological properties of D1 and D2 SPNs in the nucleus
accumbens core, which contributes to our knowledge of ventral striatal circuitry.
PMID- 29962017
TI - In Vitro Evaluation of Adhesion of Candida albicans on CAD/CAM PMMA-Based
Polymers.
AB - PURPOSE: To compare the amount of adherent Candida albicans to different CAD/CAM
poly(methyl methacrylate) (PMMA)-based polymers and conventional heat-polymerized
PMMA after long-term thermal cycling. MATERIALS AND METHODS: The specimens were
subjected to 10,000 thermal cycles (5-55 degrees C) and divided into two groups,
uncoated and pellicle-coated. Surface roughness and contact angles of the
specimens were measured. The surface morphology was observed with scanning
electron microscopy (SEM). An adhesion test was performed by incubating the disk
specimens in C. albicans suspensions at 37 degrees C for 2 hours, and the
adherent cells were counted under an optical microscope. The data were analyzed
statistically using a variance analysis and Tukey HSD post hoc comparison test.
The correlation between measurements was tested using a Pearson correlation
analysis (alpha = 0.05). RESULTS: CAD/CAM polymers generally showed statistically
significant lowest Ra and contact angle values, whereas conventional PMMA showed
the highest Ra and contact angle values in the uncoated group (p < 0.05).
Pellicle coating essentially increased contact angle of all materials and reduced
the differences in a number of Candida cells on the materials (p < 0.05). Candida
adhesion was statistically significantly greatest on conventional PMMA when
compared to CAD/CAM polymers. A strong positive correlation was found between the
surface roughness of the specimens (p < 0.05) and the amount of adhered cells,
whereas no correlation was found between hydrophobicity of the specimens and the
amount of adhered cells (p > 0.05). CONCLUSIONS: CAD/CAM PMMA-based polymers may
be preferable to reduce Candida-associated denture stomatitis in long-term use.
PMID- 29962018
TI - Integrating threshold concepts with reflective practice: Discussing a theory
based approach for curriculum refinement in dental education.
AB - INTRODUCTION: The theory of threshold concepts (TCs) is a burgeoning area of
educational research and curriculum reform. This study describes and reviews the
TCs literature, describes the differences between TCs and threshold learning
outcomes (TLOs) and seeks to promote discussion on using an integrated reflective
practice approach to facilitate the translation of TCs into fulfilment of TLOs. A
worked example is included in this study to explore the challenges inherent in
this task but also the learning gains to be made for both staff and students in
this endeavour. INTERSECTION OF REFLECTIVE CLINICAL PRACTICE AND THRESHOLD
CONCEPTS: Reflection is intrinsic to all aspects of learning and is a vital
characteristic of developing competence in the health professions. Further, the
need for explicit teaching and assessment of reflection in health professions
education is recognised. We suggest that the identification of TCs can help to
scaffold reflective processes in dentistry and argue that TCs may achieve a
bridging function between theory and practice when used in conjunction with
reflective writing and dialogue. This study provides a discussion of the
complexities and challenges involved as well as an explicit example of the
process involved for 1 TC in 1 particular discipline-removable prosthodontics.
DISCUSSION: Reflective practice is recognised by the authors as a pedagogical
tool to support the acquisition of threshold concepts. An example is provided of
integrating reflective practice tasks with identified TCs in curricula which
shows the potential of reflective dialogue and discourse as vehicles to make TCs
explicit as well as facilitate the attainment of threshold learning outcomes or
graduate attributes. This is an ongoing process, and although the fully revised
curriculum is not ready to be translated to other contexts, we suggest it is
beneficial to start working towards the integration of reflective practice tasks
and identified TLOs as part of curriculum refinement-rather than adding to a
crowded curriculum. We suggest such an integrated approach can harness the
challenges inherent in discipline-specific contexts to bridge the theory-practice
nexus for students and permit staff greater flexibility in the teaching and
assessment of such traditionally difficult areas. SUMMARY: We propose a way of
thinking about curriculum change by integrating threshold concepts with the
explicit use and assessment of reflective practice tasks as a means to achieve
threshold learning outcomes and professional attributes identified by accrediting
bodies. We provide an overview of the literature in this area and an example of
our approach in linking reflective practice with newly identified threshold
concepts in our School. We welcome further discussion, debate and collaboration
in this area.
PMID- 29962019
TI - A comparison of the EU and US regulatory frameworks for the active substance
registration of microbial biological control agents.
AB - BACKGROUND: Microbial biological control agents (MBCA) are biopesticides based on
living microbes. They have huge potential for the control of pests and diseases,
but have trouble reaching the European Union (EU) market. According to several
authors, this is caused by the regulatory regime, which is less supportive
compared with that in the USA. The main objective of this paper is to present
regulatory differences between the USA and the EU, and the resulting effects and
developments of registration in both regions. RESULTS: Results show that EU
registration is more complex due to differences between EU- and Member State (MS)
level processes, large actor heterogeneity and low flexibility. As a result, EU
registration takes, on average, ~ 1.6 years longer than US registration.
Regulatory amendments have improved EU-level processes and led to a significant
contraction of procedural time spans, but processes at the MS level have not
improved and have become a larger procedural obstacle. CONCLUSION: The results
correspond with the idea that EU registration is complex and lengthy compared
with that in the USA. To improve regulation, national-level processes should be
targeted for amendment. To that end, the authors suggest various ways of
expanding the registration capacity of MS. (c) 2018 The Authors. Pest Management
Science published by John Wiley & Sons Ltd on behalf of Society of Chemical
Industry.
PMID- 29962020
TI - An attempt to incorporate effect of direct interaction between a ligand and
explicit water molecules into MM/3D-RISM.
AB - Endpoint methods using continuum-solvent models are widely used to estimate
protein-ligand affinity. A recently developed method, MM/3D-RISM, estimates the
solvation energy using statistical mechanics by 3D-RISM. This method is
theoretically expected to accurately describe solvation effects and to also be
less dependent on protein-ligand systems. In this study, we examined the
performance of MM/3D-RISM for a set of alpha-thrombin inhibitors with a non
congeneric series of ligands, containing three diverse chemical scaffolds. The
standard MM/3D-RISM showed a weak correlation (R2 = 0.191) but correctly
estimated affinity for two of the three scaffolds. However, the simplest
inhibitor, benzamidine, was not ranked appropriately. From visual inspection of
inhibitor-binding modes, an attempt was made to incorporate the direct
interaction between a ligand and water molecules into MM/3D-RISM. A model (Model
1) dealing with directly interacting water molecules (Wat) as an independent
component of a protein (R)-ligand (L) complex-formation, that is, R + L + Wat ->
R-L-Wat, showed a better linearity (R2 = 0.422) than that of the standard MM/3D
RISM model and achieved a good ranking of all three scaffolds of alpha-thrombin
inhibitors. Additionally, an attempt was made to model avidin-biotin system with
a congeneric series of inhibitors, and results showed that both the standard
MM/3D-RISM model (R2 = 0.839) and Model-1 (R2 = 0.695) satisfactorily estimated
the affinity.
PMID- 29962021
TI - Six novel HLA-B, -DRB1, and -DQB1 alleles identified in Brazilian individuals.
AB - The novel HLA alleles B*40:331, B*40:343, B*42:24, DRB1*01:74, DQB1*03:243, and
DQB1*03:02:20 were identified in Brazilian individuals.
PMID- 29962022
TI - Cognitive and visual diagnostic errors in dermatology: part 1.
AB - Sir William Osler famously, and ironically, stated that 'Medicine is a science of
uncertainty and an art of probability'. The processes by which each physician
metes out diagnostic uncertainty and navigates probabilities in dermatology is
far from uniform. While certain ubiquitous cognitive and visual heuristics can
enhance diagnostic speed, they also create pitfalls and thinking traps that
introduce significant variation in the diagnostic process. Discussed in this part
of a two-part article are various cognitive and visual heuristics as they pertain
to skin disease, with an introduction and special attention paid to the heuristic
methods classically applied by dermatologists. How to best address error and
improve our thought processes will be addressed in part 2.
PMID- 29962023
TI - Basal cell carcinoma in a 17 year-old organ transplant recipient.
AB - Skin cancer is among the most frequent cancers in pediatric organ transplant
recipients. We report a 17-year-old Caucasian girl who had had a kidney
transplant 6 years before and was referred to our outpatient clinic for a basal
cell carcinoma of the scalp. This case emphasizes the importance of teaching sun
protective behavior to transplant recipients and their parents and having a high
index of suspicion and arrange for early referral for dermatologic care if skin
changes are observed.
PMID- 29962024
TI - Extreme Reconfigurable Nanoelectronics at the CaZrO3 /SrTiO3 Interface.
AB - Complex oxide heterostructures have fascinating emergent properties that
originate from the properties of the bulk constituents as well as from
dimensional confinement. The conductive behavior of the polar/nonpolar LaAlO3
/SrTiO3 interface can be reversibly switched using conductive atomic force
microscopy (c-AFM) lithography, enabling a wide range of devices and physics to
be explored. Here, extreme nanoscale control over the CaZrO3 /SrTiO3 (CZO/STO)
interface, which is formed from two materials that are both nonpolar, is
reported. Nanowires with measured widths as narrow as 1.2 nm are realized at the
CZO/STO interface at room temperature by c-AFM lithography. These ultrathin
nanostructures have spatial dimensions at room temperature that are comparable to
single-walled carbon nanotubes, and hold great promise for alternative oxide
based nanoelectronics, as well as offer new opportunities to investigate the
electronic structure of the complex oxide interfaces. The cryogenic properties of
devices constructed from quasi-1D channels, tunnel barriers, and planar gates
exhibit gate-tunable superconductivity, quantum oscillations, electron pairing
outside of the superconducting regime, and quasi-ballistic transport. This newly
demonstrated ability to control the metal-insulator transition at nonpolar oxide
interface greatly expands the class of materials whose behavior can be patterned
and reconfigured at extreme nanoscale dimensions.
PMID- 29962025
TI - Static and dynamic connectomics differentiate between depressed patients with and
without suicidal ideation.
AB - Neural circuit dysfunction underlies the biological mechanisms of suicidal
ideation (SI). However, little is known about how the brain's "dynome"
differentiate between depressed patients with and without SI. This study included
depressed patients (n = 48) with SI, without SI (NSI), and healthy controls (HC,
n = 30). All participants underwent resting-state functional magnetic resonance
imaging. We constructed dynamic and static connectomics on 200 nodes using a
sliding window and full-length time-series correlations, respectively.
Specifically, the temporal variability of dynamic connectomic was quantified
using the variance of topological properties across sliding window. The overall
topological properties of both static and dynamic connectomics further
differentiated between SI and NSI, and also predicted the severity of SI. The SI
showed decreased overall topological properties of static connectomic relative to
the HC. The SI exhibited increases in overall topological properties with regard
to the dynamic connectomic when compared with the HC and the NSI. Importantly,
combining the overall topological properties of dynamic and static connectomics
yielded mean 75% accuracy (all p < .001) with mean 71% sensitivity and mean 75%
specificity in differentiating between SI and NSI. Moreover, these features may
predict the severity of SI (mean r = .55, all p < .05). The findings revealed
that combining static and dynamic connectomics could differentiate between SI and
NSI, offering new insight into the physiopathological mechanisms underlying SI.
Furthermore, combining the brain's connectome and dynome may be considered a
neuromarker for diagnostic and predictive models in the study of SI.
PMID- 29962027
TI - Effects of hot air treatment in combination with Pichia guilliermondii on
postharvest preservation of peach fruit.
AB - BACKGROUND: Antagonistic yeast and hot air treatment are two promising methods
for conferring resistance to pathogenic fungi. The study assessed the
effectiveness of hot-air treatment (45 degrees C, 4 h) and antagonistic yeast
(Pichia guilliermondii at 108 CFU mL-1 ) alone or in combination on the two
major postharvest diseases (Rhizopus stolonifer and Penicillium expansum), as
well as the quality and antioxidant parameters in harvested peaches. RESULTS: The
combination of hot-air treatment and Pichia guilliermondii had notable inhibitory
effects on infections in peach fruit wounds. In addition, the individual hot-air
treatment or Pichia guilliermondii could improve quality indexes to varying
degrees, but the combination of the above two treatments could achieve the
highest efficacy. Furthermore, compared with other groups, the combined treatment
induced the highest activities of superoxide dismutase and catalase, improved the
content of total phenolics and reduced glutathione most obviously. Lastly, the
most significant reductions in malondialdehyde content and relative electrical
conductivity were observed in the combination-treated fruit. CONCLUSIONS: The
combined treatment could control fungal diseases, besides delay the decline of
quality and antioxidant parameters, so as to achieve the purpose of fresh keeping
for harvested peach fruit. (c) 2018 Society of Chemical Industry.
PMID- 29962026
TI - SPECT/CT image-based dosimetry for Yttrium-90 radionuclide therapy: Application
to treatment response.
AB - This work demonstrates the efficacy of voxel-based 90 Y microsphere dosimetry
utilizing post-therapy SPECT/CT imaging and applies it to the prediction of
treatment response for the management of patients with hepatocellular carcinoma
(HCC). A 90 Y microsphere dosimetry navigator (RapidSphere) within a commercial
platform (Velocity, Varian Medical Systems) was demonstrated for three
microsphere cases that were imaged using optimized bremsstrahlung SPECT/CT. For
each case, the 90 Y SPECT/CT was registered to follow-up diagnostic MR/CT using
deformable image registration. The voxel-based dose distribution was computed
using the local deposition method with known injected activity. The system
allowed the visualization of the isodose distributions on any of the registered
image datasets and the calculation of dose-volume histograms (DVHs). The
dosimetric analysis illustrated high local doses that are characteristic of blood
flow directed brachytherapy. In the first case, the HCC mass demonstrated a
complete response to treatment indicated by a necrotic region in follow-up MR
imaging. This result was dosimetrically predicted since the gross tumor volume
(GTV) was well covered by the prescription isodose volume (V150 Gy = 85%). The
second case illustrated a partial response to treatment which was characterized
by incomplete necrosis of an HCC mass and a remaining area of solid enhancement
in follow-up MR imaging. This result was predicted by dosimetric analysis because
the GTV demonstrated incomplete coverage by the prescription isodose volume (V470
Gy = 18%). The third case demonstrated extrahepatic activity. The dosimetry
indicated that the prescription (125 Gy) isodose region extended outside of the
liver into the duodenum (178 Gy maximum dose). This was predictive of toxicity as
the patient later developed a duodenal ulcer. The ability to predict outcomes and
complications using deformable image registration, calculated isodose
distributions, and DVHs, points to the clinical utility of patient-specific dose
calculations for 90 Y radioembolization treatment planning.
PMID- 29962028
TI - A novel HLA-A null allele, HLA-A*66:28N.
AB - The novel HLA-A*66:28N allele differs from HLA-A*66:03 by a single nucleotide
deletion at codon 185.
PMID- 29962029
TI - Editorial Comment to Psychotherapy combined with drug therapy in patients with
category III chronic prostatitis/chronic pelvic pain syndrome: A randomized
controlled trial.
PMID- 29962030
TI - Primum non nocere: Minocycline-induced liver injury in a teenager.
PMID- 29962031
TI - Barriers and facilitators to implementing a process to enable parent escalation
of care for the deteriorating child in hospital.
AB - OBJECTIVE: To identify barriers and facilitators to implementing a parent
escalation of care process: Calling for Help (C4H). DESIGN: Audits, semi
structured interviews and focus groups guided by the Theoretical Domains
Framework. SETTING: Australian paediatric hospital where a parent escalation of
care process was introduced in the previous 6 months. PARTICIPANTS: Four
children, 13 parents, 91 nurses and doctors including Medical Emergency Team
(MET) members. MAIN OUTCOME MEASURES: Parent awareness and involvement in
escalating care and factors impacting implementation of C4H. RESULTS: Two audits
identified low level of parent awareness (16/88, 19% and 5/85, 6%). Parent
involvement in escalation of care was documented in 11/62 (18%) events. The main
facilitators included uniformly positive views that C4H was in the child's best
interest, acknowledgement that parents had skills to recognize deterioration and
would take action. C4H was considered to add to patient safety and being reviewed
by the MET was a patient benefit. Key barriers were the low level of awareness,
doubt about parent capabilities, concern about parents' information overload,
anticipated overuse of resources, staff unease about possible repercussions and
anticipated difficulty for parents to question staff with potential negative
effects on parent-staff relationships. Overall C4H presents a challenge to
traditional hospital hierarchy and culture. CONCLUSIONS: Although there was a low
level of awareness about C4H in practice, there was in-principle support for the
concept. Initial strategies had primarily targeted policy change without taking
into account the need for practice and organizational behaviour changes. Using a
theoretical approach to identify key factors will enable a targeted approach to
implementation.
PMID- 29962032
TI - Early cirrhosis and a preserved bone marrow niche favour regenerative response to
growth factors in decompensated cirrhosis.
AB - BACKGROUND: Exogenous growth factor-mobilized bone marrow (BM) stem cells have
shown a differential response in the management of decompensated cirrhosis (DC).
This study was designed to evaluate potential clinical benefit of adding
Erythropoietin (EPO) in granulocyte-colony stimulating factor (G-CSF)-mobilized
stem cell therapy, possible mechanisms of regeneration and predictive factors of
regenerative response. METHODS: Sixty consecutive DC patients received either G
CSF with EPO (Group A; n = 30) or G-CSF and placebo (Group B; n = 30) for 2
months and were carefully followed up for 1 year. Baseline and post-treatment
liver biopsy, BM biopsy and BM aspirate were analysed for fibro-inflammatory and
regenerative response and BM hematopoietic reservoir. RESULTS: Addition of EPO to
G-CSF showed a significant improvement in Child-Pugh score (P = 0.03) and MELD
score (P = 0.003) as compared to G-CSF alone, with reduction in mortality (16.6%
vs 36.7%, P = 0.09). The combination arm also demonstrated a decreased incidence
of acute kidney injury (P < 0.001), encephalopathy (P = 0.005) and refilling of
ascites (P = 0.03). Compared to monotherapy, it increased CD163+ macrophages (P =
0.013), Ki67+ index (P < 0.001) with decrease in alpha-SMA levels (P < 0.001) in
liver tissue. The response was better with grade 1 and 2 than with grade 3
ascites; Child B cirrhosis and MELD < 16. Non-responders had lower hematopoietic
stem cells (HSCs) at baseline. On multivariate analysis, the liver disease
severity (MELD < 16) and a relatively preserved BM (BM-HSCs > 0.4) predicted
therapeutic response (AUROC = 0.82). CONCLUSIONS: Early DC (MELD < 16) patients
with mild-moderate ascites and those with a healthy cellular baseline BM respond
better to growth factor therapy. Addition of EPO to G-CSF provides better
regenerative response than G-CSF monotherapy.
PMID- 29962033
TI - Inactivation of Vibrio sp. in pure cultures and mussel homogenates using high
hydrostatic pressure.
AB - : The objective of this study was to determine the effect of high hydrostatic
pressure (HHP) on the inactivation of Vibrio sp. in pure cultures and mussel
homogenates. Four Vibrio strains including V. alginolyticus, V. cholerae, V.
parahaemolyticus and V. vulnificus were used. HHP treatments were performed with
both pure Vibrio sp. cultures in alkaline peptone water (2% NaCl) and
artificially inoculated mussel homogenates at pressure levels of 250, 350 and 450
MPa for 1 and 3 min at 25 degrees C. Counts of Vibrio were determined before and
after treatment using drop plating method. The effect of high pressure on the
reduction level significantly differed among the respective Vibrio species.
Vibrio vulnificus was the most susceptible species to HHP. To achieve a >5 log
reduction in mussel homogenates, pressure treatment needs to be (i) 350-450 MPa
for >=1 min at 25 degrees C for both V. alginolyticus and V. cholerae, (ii) 250
MPa for >=3 min or 350-450 MPa for >=1 min for V. vulnificus and (iii) 350 MPa
for >=3 min or 450 MPa for >=1 min for V. parahaemolyticus. SIGNIFICANCE AND
IMPACT OF THE STUDY: High hydrostatic pressure (HHP) has been applied to
inactivate spoilage and pathogenic micro-organisms in a variety of food products,
including seafood. Vibrio sp. are frequently reported as the main cause of
foodborne illness associated with consumption of raw or undercooked seafood
particularly shellfish worldwide. To date, data on the inactivation of Vibrio sp.
via HHP are still limited and most of the trials only investigated HHP
application in oysters and clams. This study demonstrates the efficacy of HHP
inactivating Vibrio sp. in both pure culture and mussel homogenates.
PMID- 29962034
TI - Therapeutic effect of simvastatin on DMBA-induced breast cancer in mice.
AB - Preclinical studies have shown positive effects of statins against specific
cancers. This study aimed to determine the therapeutic effect of simvastatin in
12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer. Female albino mice
were divided into two groups, with or without DMBA administration. After tumor
appearance, DMBA-treated group was further divided into four groups (D1-D4) as
control (D1), treated with simvastatin at 80 and 40 mg/kg/day, orally (D2 and D3)
and tamoxifen (50 mg/kg/day, orally) treated group (D4). After 4 weeks, animals
were sacrificed, serum samples were collected and tumors were dissected for
histopathological study and determination of selected parameters. The tumor
marker carcinoma antigen 15-3 (CA15-3), oxidative stress parameters and
prostaglandin E2 (PGE2) levels were analyzed in serum and tumors in experimental
groups. Tamoxifen and high dose of simvastatin improved parameters of mammary
carcinogenesis including mean tumor volume, body weight and percent of mortality
as compared to mice with breast tumors without treatment (D1). Additionally,
simvastatin usage increased total antioxidant capacity (TAC) level, paraoxonase 1
(PON1) activity in serum and decreased total oxidant status (TOS) and
malondialdehyde (MDA) levels in tumors similar to tamoxifen. No significant
decrease was found in serum CA 15-3 and tumor PGE2 levels in simvastatin and
tamoxifen treated groups as compared to D1 group. These data suggest that
simvastatin has anticancer effects which are relatively similar to that of
tamoxifen in an animal model of breast cancer.
PMID- 29962035
TI - Haploidentical haematopoietic stem cell transplantation for thalassaemia major
based on an FBCA conditioning regimen.
AB - Allogeneic haematopoietic stem cell transplantation (HSCT) is the only available
curative therapy for patients with thalassaemia major. With the progress in human
leucocyte antigen (HLA) antigen typing technology and supportive care, the
outcomes of thalassaemia major have greatly improved in recent years, even in
high-risk patients. However, the problem of finding a suitable donor is still a
major obstacle to curing these patients. In recent decades, the lack of available
HSCT donors has led to the increased use of haploidentical donors (HDs) for HSCT
in haematological malignancies. Recently, we explored the effect of HD HSCT to
eight children with thalassaemia major based on the FBCA conditioning regimen
(fludarabine, busulphan, cyclophosphamide, antithymocyte globulin), which is
usually used in leukaemia patients receiving haploidentical HSCT in our centre.
So far, all of the transplanted patients have a stable engraftment and are
transfusion independent in daily life. This encouraging result has revised our
previous conception about haploidentical HCST for thalassaemia major and strongly
suggests that HD HSCT is a feasible and safe method for thalassaemia major
patients.
PMID- 29962036
TI - Quantum mechanical studies on dioxin-imprinted polymer precursor composites:
Fundamental insights to enhance the binding strength and selectivity of
biomarkers.
AB - We present a benchmark study of binding energies for dioxin-imprinted polymer
complexes. A density functional theory approach was used for screening the
polymerization precursors in the rational design of molecularly imprinted
polymers (MIPs). Tetrachlorodibenzo-p-dioxin (TCDD) was taken as an imprinted
molecule. The geometry optimization, natural bond orbital charge, and molecular
electrostatic potential of TCDD and acrylamide (AM) were studied at the M062X
level and 6-31G(d,p) belonging to one of the hybrid density functional theories.
The results of molecular electrostatic potential and natural bond orbital charge
analysis were comparable. Among the studied functional monomers-AM, methacrylic
acid (MAA), itaconic acid, and vinyl pyridine-AM was confirmed as the best
functional monomer, because the strongest interaction (the maximum number of
hydrogen bonds and the lowest binding energy) occurs between TCDD and AM. The
stability property was excellent when the ratio of TCDD and AM was 1:4. The
polarizable continuum model was used for solvent calculations. Computational
results showed that acetonitrile plays an important role in the MIP formation, as
it seems to control the size and the shape of the cavity. The atoms in molecule
and Becke surface method have also been applied to understand the nature and
strength of the hydrogen bonding interactions in complexes. TCDD-AM complexes
were found involving C-O...Cl and N-H...Cl hydrogen bonds. Good correlations have
been established between hydrogen bond lengths versus atoms in molecule
topological parameter like electron density rho(r) and its Laplacian ?2 rho(r) at
the bond critical points. On ground of theoretical results, a series of MIPs were
synthesized. The MIP prepared using TCDD as the template, the functional monomer
(AM), and the cross-linker (TRIM) in acetonitrile solvent exhibited the highest
adsorption capacity for TCDD. The maximum binding capacity of TCDD on the MIP was
3.7 MUg/mg. This research work can provide a theoretical reference for the
fabrication and characterization of novel TCDD-MIPs for environmental
applications.
PMID- 29962037
TI - An evaluation of preoperative anxiety in Spanish-speaking and Latino children in
the United States.
AB - BACKGROUND: There is a large body of literature examining factors associated with
children's preoperative anxiety; however, cultural variables such as ethnicity
and language have not been included. AIMS: The purpose of this investigation was
to examine the role of Latino ethnicity and Spanish-speaking families in
pediatric preoperative anxiety. METHODS: Participants were 294 children aged 2-15
years of age undergoing outpatient, elective tonsillectomy and/or adenoidectomy
surgery and general anesthesia. Participants were recruited and categorized into
3 groups: English-speaking non-Latino White (n = 139), English-speaking Latino (n
= 88), and Spanish-speaking Latino (n = 67). Children's anxiety was rated at 2
time points before surgery: the time the child entered the threshold of the
operating room (Induction 1) and the time when the anesthesia mask was placed
(Induction 2). RESULTS: Results from separate linear regression models at
Induction 1 and Induction 2, respectively, showed that being from a Spanish
speaking Latino family was associated with higher levels of preoperative anxiety
compared with being from an English-speaking family. In addition, young age and
low sociability was associated with higher preoperative anxiety in children.
CONCLUSION: Clinicians should be aware that younger, less sociable children of
Spanish-speaking Latino parents are at higher risk of developing preoperative
anxiety and manage these children based on this increased risk.
PMID- 29962038
TI - Identification of a unique Staphylococcus aureus ribosomal signature in severe
atopic dermatitis.
PMID- 29962039
TI - Emerging evidence for the modulation of exocytosis by signalling lipids.
AB - Membrane fusion is a key event in exocytosis of neurotransmitters and hormones
stored in intracellular vesicles. In this process, soluble N-ethylmaleimide
sensitive factor attachment protein receptor (SNARE) proteins are essential
components of the exocytotic molecular machinery, while lipids have been seen
traditionally as structural elements. However, the so-called signalling lipids,
such as sphingosine and arachidonic acid, interact with SNAREs and directly
modulate the frequency and mode of fusion events. Interestingly, recent work has
proved that the sphingosine analogue FTY-720, used in the treatment of multiple
sclerosis, mimics the effects of signalling lipids. In the present Review, we
discuss recent investigations suggesting that endogenous signalling lipids and
synthetic analogues can modulate important physiological aspects of secretion,
such as quantal release, vesicle recruitment into active sites, vesicle transport
and even organelle fusion in the cytosol. Therefore, these compounds are far from
being merely structural components of cellular membranes.
PMID- 29962041
TI - Oxygen-Vacancy and Surface Modulation of Ultrathin Nickel Cobaltite Nanosheets as
a High-Energy Cathode for Advanced Zn-Ion Batteries.
AB - The development of high-capacity, Earth-abundant, and stable cathode materials
for robust aqueous Zn-ion batteries is an ongoing challenge. Herein, ultrathin
nickel cobaltite (NiCo2 O4 ) nanosheets with enriched oxygen vacancies and
surface phosphate ions (P-NiCo2 O4-x ) are reported as a new high-energy-density
cathode material for rechargeable Zn-ion batteries. The oxygen-vacancy and
surface phosphate-ion modulation are achieved by annealing the pristine NiCo2 O4
nanosheets using a simple phosphating process. Benefiting from the merits of
substantially improved electrical conductivity and increased concentration of
active sites, the optimized P-NiCo2 O4-x nanosheet electrode delivers remarkable
capacity (309.2 mAh g-1 at 6.0 A g-1 ) and extraordinary rate performance (64%
capacity retention at 60.4 A g-1 ). Moreover, based on the P-NiCo2 O4-x cathode,
our fabricated P-NiCo2 O4-x //Zn battery presents an impressive specific capacity
of 361.3 mAh g-1 at the high current density of 3.0 A g-1 in an alkaline
electrolyte. Furthermore, extremely high energy density (616.5 Wh kg-1 ) and
power density (30.2 kW kg-1 ) are also achieved, which outperforms most of the
previously reported aqueous Zn-ion batteries. This ultrafast and high-energy
aqueous Zn-ion battery is promising for widespread application to electric
vehicles and intelligent devices.
PMID- 29962043
TI - Role of hemodynamics in initiation/growth of intracranial aneurysms.
AB - BACKGROUND: Intracranial aneurysm (IA) is a disease of the vascular wall
resulting in abnormal enlargement of the vessel lumen. It is a common pathology
with a prevalence of 2%-3% in the adult population. IAs are mostly small,
quiescent and asymptomatic; yet, upon rupture, severe brain damage or even death
is frequently encountered. In addition to clinical factors, hemodynamic forces,
mainly wall shear stress (WSS), have been associated with the initiation of IAs
and possibly with their risk of rupture. However, the mechanism by which WSS
contributes to aneurysm growth and rupture is not completely understood. DESIGN:
PubMed and Ovid MEDLINE databases were searched. In addition, key review articles
were screened for relevant original publications. RESULTS: Current knowledge
about the relation between WSS and IA has been obtained from both computational
fluid dynamic studies in patients and experimental models of IA formation and
growth. It is increasingly recognized that a high wall shear stress (gradient)
participates to IA formation and that both low and high WSS can drive IA growth.
Primary cilia (PC) play an important role as mechanosensors as patients with
polycystic kidney disease, which is characterized by the absence or dysfunction
of PC, have increased risk to develop IAs as well as increased risk of rupture.
CONCLUSION: Wall shear stress is a key player in IA initiation and progression.
It is involved in vascular wall remodelling and inflammation, processes
underlying aneurysm pathophysiology.
PMID- 29962042
TI - A Natural Biopolymer Film as a Robust Protective Layer to Effectively Stabilize
Lithium-Metal Anodes.
AB - Li metal is considered as an ideal anode for Li-based batteries. Unfortunately,
the growth of Li dendrites during cycling leads to an unstable interface, a low
coulombic efficiency, and a limited cycling life. Here, a novel approach is
proposed to protect the Li-metal anode by using a uniform agarose film. This
natural biopolymer film exhibits a high ionic conductivity, high elasticity, and
chemical stability. These properties enable a fast Li-ion transfer and feasiblity
to accomodate the volume change of Li metal, resulting in a dendrite-free anode
and a stable interface. Morphology characterization shows that Li ions migrate
through the agarose film and then deposit underneath it. A full cell with the
cathode of LiFPO4 and an anode contaning the agarose film exhibits a capacity
retention of 87.1% after 500 cycles, much better than that with Li foil anode
(70.9%) and Li-deposited Cu anode (5%). This study provides a promising strategy
to eliminate dendrites and enhance the cycling ability of lithium-metal batteries
through coating a robust artificial film of natural biopolymer on lithium-metal
anode.
PMID- 29962040
TI - Racial disparities in fifth-grade sun protection: Evidence from the Healthy
Passages study.
AB - BACKGROUND/OBJECTIVES: Despite rising skin cancer rates in children, multiple
studies reveal inadequate youth sun-protective behavior (eg, sunscreen use).
Using Healthy Passages data for fifth-graders, we set out to determine sunscreen
adherence in these children and investigated factors related to sunscreen
performance. METHODS: Survey data were collected from 5119 fifth-graders and
their primary caregivers. Logistic regression was used to assess associations
between sunscreen adherence and performance of other preventive health behaviors
(eg, flossing, helmet use) and examine predictors of sunscreen adherence.
Analyses were repeated in non-Hispanic black, Hispanic, and non-Hispanic white
subgroups. RESULTS: Five thousand one hundred nineteen (23.4%) children almost
always used sunscreen, 5.9% of non-Hispanic blacks (n = 1748), 23.7% of Hispanics
(n = 1802), and 44.8% of non-Hispanic whites (n = 1249). Performing other
preventive health behaviors was associated with higher odds of sunscreen
adherence (all P < .001), with the greatest association with flossing teeth (odds
ratio = 2.41, 95% confidence interval = 1.86-3.13, P < .001). Factors for lower
odds of sunscreen adherence included being male and non-Hispanic black or
Hispanic and having lower socioeconomic status. School-based sun-safety education
and involvement in team sports were not significant factors. CONCLUSION: Our data
confirm low use of sun protection among fifth-graders. Future research should
explore how public health success in increasing prevalence of other preventive
health behaviors may be applied to enhance sun protection messages. Identifying
risk factors for poor adherence enables providers to target patients who need
more education. Improving educational policies and content in schools may be an
effective way to address sun safety.
PMID- 29962044
TI - Inpatient burden of pediatric dermatology in the United States.
AB - BACKGROUND/OBJECTIVES: It is known that inpatient care accounts for a significant
portion of health care expenditures, but the national burden of inpatient
pediatric dermatology is poorly characterized. We sought to assess risk factors,
conditions, and financial costs associated with pediatric hospitalizations for
skin disease. METHODS: We performed a cross-sectional study of pediatric
dermatology hospitalizations using the 2012 Kids' Inpatient Database, which
samples 80% of non-birth-related pediatric admissions from 44 states to generate
national estimates. The demographic characteristics of children admitted for
dermatologic and nondermatologic conditions were compared, and the financial
costs of these admissions were analyzed. RESULTS: In 2012, there were 74 229 (95%
confidence interval (CI) = 68 620-79 978) pediatric dermatology hospitalizations,
accounting for 4.2% of all pediatric admissions and $379.8 million (95% CI =
$341.3-418.4 million) in health care costs. Bacterial infections (n = 59 115, 95%
CI = 54 669-63 561), viral diseases (n = 3812, 95% CI = 3457-4167), and
noncancerous skin growths (n = 2931, 95% CI = 2318-3545) were the most common
conditions requiring hospitalization. The highest mean cost per hospitalization
was for admissions for cutaneous lymphomas ($58 294, 95% CI = $31 694-84 893),
congenital skin abnormalities ($24 186, 95% CI = $16 645-31 728), and ulcers ($17
064, 95% CI = $14 683-19 446). Pediatric dermatology hospitalizations were most
strongly associated with living in a low-income community (odds ratio (OR) =
1.22, 95% CI = 1.16-1.29) and the South (OR = 1.32, 95% CI = 1.19-1.46) and being
uninsured (OR = 1.35, 95% CI = 1.26-1.45) or having Medicaid insurance (OR =
1.17, 95% CI = 1.13-1.22). CONCLUSION: Skin disease is a common cause of
hospitalizations in children, and there are disparities in these admissions that
could reflect inadequate access to outpatient pediatric dermatologists.
PMID- 29962045
TI - Intravascular leiomyomatosis with extension into the pulmonary artery.
PMID- 29962046
TI - MOF-Confined Sub-2 nm Atomically Ordered Intermetallic PdZn Nanoparticles as High
Performance Catalysts for Selective Hydrogenation of Acetylene.
AB - Controllable synthesis of ultrasmall atomically ordered intermetallic
nanoparticles is a challenging task, owing to the high temperature commonly
required for the formation of intermetallic phases. Here, a metal-organic
framework (MOF)-confined co-reduction strategy is developed for the preparation
of sub-2 nm intermetallic PdZn nanoparticles, by employing the well-defined
porous structures of calcinated ZIF-8 (ZIF-8C) and an in situ co-reduction
therein. HAADF-STEM, HRTEM, and EDS characterizations reveal the homogeneous
dispersion of these sub-2 nm intermetallic PdZn nanoparticles within the ZIF-8C
frameworks. XRD, XPS, and EXAFS measurements further confirm the atomically
ordered intermetallic phase nature of these sub-2 nm PdZn nanoparticles.
Selective hydrogenation of acetylene evaluation results show the excellent
catalytic properties of the sub-2 nm intermetallic PdZn, which result from the
energetically more favorable path for acetylene hydrogenation and ethylene
desorption over the ultrasmall particles than over larger-sized intermetallic
PdZn as revealed by density functional theory (DFT) calculations. Moreover, this
protocol is also extendable for the preparation of sub-2 nm intermetallic PtZn
nanoparticles and is expected to provide a novel methodology in synthesizing
ultrasmall atomically ordered intermetallic nanomaterials by rationally
functionalizing MOFs.
PMID- 29962047
TI - Iron-Catalyzed Synthesis of the Hexahydrocyclopenta[c]furan Core and Concise
Total Synthesis of Polyflavanostilbene B.
AB - The first synthesis of polyflavanostilbene B (1), which has seven contiguous
stereocenters including two quaternary carbon centers, from abundant polymeric (
)-epicatechin gallate on a gram scale in three steps without the use of
protecting groups is reported. The key transformations of this strategy include a
regioselective and stereoselective substitution of resveratrol to give the 4
derivative of (-)-epicatechin 3-gallate and an iron-catalyzed cyclization
reaction. The possible radical cyclization mechanism in the formation of the
hexahydrocyclopenta[c]furan core is also discussed.
PMID- 29962048
TI - MTMR4, a phosphoinositide-specific 3'-phosphatase, regulates TFEB activity and
the endocytic and autophagic pathways.
AB - Phosphatidylinositol 3-phosphate (PI(3)P) is the predominant phosphoinositide
species in early endosomes and autophagosomes, in which PI(3)P dictates traffic
of these organelles. Phosphoinositide levels are tightly regulated by lipid
kinases and -phosphatases; however, a phosphatase that converts PI(3)P back to
phosphatidylinositol in the endosomal and autophagosomal compartments is not
fully understood. We investigated the subcellular distribution and functions of
myotubularin-related protein-4 (MTMR4), which is distinct among other MTMRs in
that it possesses a PI(3)P-binding FYVE domain, in lung alveolar epithelium
derived A549 cells. MTMR4 was localized mainly in late endosomes and
autophagosomes. MTMR4 knockdown markedly suppressed the motility, fusion, and
fission of PI(3)P-enriched structures, resulting in decreases in late endosomes,
autophagosomes, and lysosomes, and enlargement of PI(3)P-enriched early and late
endosomes. In amino acid- and serum-starved cells, MTMR4 knockdown decreased both
autophagosomes and autolysosomes and markedly increased PI(3)P-containing
autophagosomes and late endosomes, suggesting that the fusion with lysosomes of
autophagosomes and late endosomes might be impaired. Notably, MTMR4 knockdown
inhibited the nuclear translocation of starvation stress responsive transcription
factor-EB (TFEB) with reduced expression of lysosome-related genes in starved
cells. These findings indicate that MTMR4 is essential for the integrity of
endocytic and autophagic pathways.
PMID- 29962050
TI - Rationale and design of a randomized study to assess the efficacy and safety of
evolocumab in patients with diabetes and dyslipidemia: The BERSON clinical trial.
AB - Type 2 diabetes mellitus (T2DM) is a major independent risk factor for
cardiovascular disease, and diabetic dyslipidemia is a major contributor to
cardiovascular risk in these patients. Here we report the rationale and design of
a phase 3, double-blind study specifically designed to evaluate the lipid
lowering efficacy of the proprotein convertase subtilisin/kexin type 9 (PCSK9)
inhibitor evolocumab in patients with T2DM and hyperlipidemia or mixed
dyslipidemia who are on background statin therapy. In the BERSON (evolocumaB
Efficacy for LDL-C Reduction in subjectS with T2DM On background statiN) trial,
patients with T2DM, a screening low-density lipoprotein cholesterol (LDL-C) level
of >= 2.6 mmol/L (>=100 mg/dL) or >= 3.4 mmol/L (>=130 mg/dL), and with or
without statin treatment at screening, respectively, were enrolled and started on
atorvastatin 20 mg/day for a lipid stabilization period of at least 4 weeks.
Then, patients were randomly assigned in a 2:2:1:1 ratio to receive atorvastatin
20 mg once daily plus either evolocumab 140 mg every 2 weeks (Q2W), evolocumab
420 mg every month (QM), placebo Q2W, or placebo QM. The co-primary outcome
measures were the percentage change from baseline in LDL-C at week 12 and the
percentage change from baseline in LDL-C at the mean of weeks 10 and 12. The
BERSON trial has completed enrollment. The study completed in the first half of
2018, and will provide information on the efficacy and safety of evolocumab in
patients with T2DM and dyslipidemia.
PMID- 29962051
TI - Establishment of a low-dosage-IPTG inducible expression system construction
method in Escherichia coli.
AB - The lac operon is a delicate inducible gene expression element in bacteria. To
efficiently induce gene expression, a sufficient dosage of an inducer, usually
that of 500-1000 uM isopropyl beta-D-1-thiogalactopyranoside (IPTG), is required
to keep repressor LacI from its binding sites, which is a heavy cost burden in
low-value-added products. So we propose a strategy to reduce the required dosage
of IPTG by restricting LacI expression. To test this strategy, we employed a
reconstructed IPTG inducible expression system based on lac operon,
Promoter(lacO)-target gene-PtacL-lacI, where a modified promoter, Ptac, with a
random synthetic library (PtacL) to instead of PlacI to optimize LacI expression
in Escherichia coli. Finally, the PtacL mutant, PtacL4, which could maintain the
same repression effect as the original PlacI while reducing the required dosage
of IPTG from 500 to 20 uM, was selected. This method is simple and efficient and
can be of a good reference point for attempts to reduce inducer concentration in
the IPTG or similar inducible expression systems.
PMID- 29962049
TI - Statistical harmonization corrects site effects in functional connectivity
measurements from multi-site fMRI data.
AB - Acquiring resting-state functional magnetic resonance imaging (fMRI) datasets at
multiple MRI scanners and clinical sites can improve statistical power and
generalizability of results. However, multi-site neuroimaging studies have
reported considerable nonbiological variability in fMRI measurements due to
different scanner manufacturers and acquisition protocols. These undesirable
sources of variability may limit power to detect effects of interest and may even
result in erroneous findings. Until now, there has not been an approach that
removes unwanted site effects. In this study, using a relatively large multi-site
(4 sites) fMRI dataset, we investigated the impact of site effects on functional
connectivity and network measures estimated by widely used connectivity metrics
and brain parcellations. The protocols and image acquisition of the dataset used
in this study had been homogenized using identical MRI phantom acquisitions from
each of the neuroimaging sites; however, intersite acquisition effects were not
completely eliminated. Indeed, in this study, we found that the magnitude of site
effects depended on the choice of connectivity metric and brain atlas. Therefore,
to further remove site effects, we applied ComBat, a harmonization technique
previously shown to eliminate site effects in multi-site diffusion tensor imaging
(DTI) and cortical thickness studies. In the current work, ComBat successfully
removed site effects identified in connectivity and network measures and
increased the power to detect age associations when using optimal combinations of
connectivity metrics and brain atlases. Our proposed ComBat harmonization
approach for fMRI-derived connectivity measures facilitates reliable and
efficient analysis of retrospective and prospective multi-site fMRI neuroimaging
studies.
PMID- 29962052
TI - Correlated, Dual-Beam Optical Gating in Coupled Organic-Inorganic Nanostructures.
AB - An optical switch with two distinct resonances is formed by combining PbS
nanocrystals and the conductive polymer poly[sodium 2-(2-ethynyl-4
methoxyphenoxy)acetate] (PAE) into a hybrid thin film. Infrared excitation of the
nanocrystals invokes charge transfer and consecutive polaron formation in the
PAE, which activates the switch for excited-state absorption at visible
frequencies. The optical modulation of the photocurrent response of the switch
exhibits highly wavelength-selective ON/OFF ratios. Transient absorption
spectroscopy shows that the polaron formation is correlated with the excited
state of the nanocrystals, opening up new perspectives for photonic data
processing. Such correlated activated absorption can be exploited to enhance the
sensitivity for one optical signal by a second light source of different
frequency as part of an optical amplifier or a device with AND logic.
PMID- 29962053
TI - Phototherapy-induced blistering reaction and eruptive melanocytic nevi in a child
with transient neonatal porphyrinemia.
AB - Neonatal blue-light phototherapy induced a blistering reaction followed by
eruption of melanocytic nevi on the exposed skin surface of a child with
transient neonatal porphyrinemia. New nevi are still developing 4 years after the
triggering event. The role of phototoxicity-induced epidermal injury, that of
porphyrins and the influence of neonatal blue-light therapy, in this unique
phenomenon are discussed.
PMID- 29962054
TI - Childhood nutrition and cardiovascular disease risk: People in training for a
plant-centered diet.
PMID- 29962055
TI - Photopatch and patch testing in 63 patients with frontal fibrosing alopecia: a
case series.
PMID- 29962056
TI - Normative reference data, determinants, and clinical implications of right atrial
reservoir function in women assessed by 2D speckle-tracking echocardiography.
AB - AIM: We aim to determine normative reference data of phasic right atrial (RA)
strain and to investigate determinants, possible clinical implications as well as
feasibility and reproducibility of RA strain analysis. METHODS AND RESULTS: Right
atrial strain was analyzed in 266 participants of the cross-sectional Berlin
Female Risk Evaluation (BEFRI) study using 2D speckle-tracking echocardiography
(2D STE). To determine reference values, phasic RA strain was determined in a
subgroup of 123 individuals without known cardiovascular diseases or risk
factors. Mean RA reservoir strain (RAS), RA conduit, and contraction strain in
this reference group were 44.9 +/- 11.6%, 27.1 +/- 9.5%, and 17.0 +/- 5.9%,
respectively. Regarding possible clinical implications, RAS was significantly
reduced in women with a BMI >= 25, compared with women with a BMI < 25 (35.5 +/-
11.1% vs 43.4 +/- 11.6%, P < 0.0001). RA strain analysis showed a good
feasibility (92.7%); intra- and inter-observer variability was low (<5%). BMI,
global longitudinal peak systolic LV strain (LVGLS%), RA area, TAPSE, and early
diastolic myocardial relaxation velocity of the RV (RV-e') were significantly
associated with RA mechanics in a multivariate logistic regression analysis.
CONCLUSION: In this cross-sectional trial, we determined reference values,
feasibility and reproducibility, clinical and echocardiographic determinants, and
possible clinical implications of RA strain analysis. Our data may help to
introduce the analysis of RA mechanics into future echocardiographic routine use.
PMID- 29962057
TI - Materials with Nanoscale Porosity: Energy and Environmental Applications.
AB - In this personal account, several key inventions on designing novel microporous
and mesoporous materials, and their applications in energy and environmental
research are reviewed. Although, crystalline materials with sub-nanometer pore
size regime like zeolites, AlPOs, MOFs, ZIFs etc. are known over the years,
silicious and non-silicious mesoporous materials have revolutionized the research
on the materials with nanoscale porosity in last two and half decades. A wide
range of inorganic, organic-inorganic hybrid as well as purely organic mesoporous
materials with either periodic or disordered mesopores are known. Apart from
conventional hydrothermal syntheses involving soft templating route, hard
templating, evaporation induced self-assembly (EISA), electrochemical or
solvothermal (using hydrophilic solvents) synthetic routes are often employed in
designing a large spectrum of mesoporous materials. Ease of synthesis using
available cheap raw chemicals and versatility in the framework compositions
together with the unique surface properties like exceptionally high surface area,
pore volume and tunability in pore dimensions have made these materials very
exciting to a wide range of researchers working on materials chemistry. Nanoscale
porosity in the semiconductor nanomaterials is highly beneficial for the
photocatalytic, optoelectronic and related light-harvesting applications. Their
high chemical stability has been explored intensively in designing novel
heterogeneous catalysts for the synthesis of biofuels from biomass or CO2
fixation to reactive organic molecules for the synthesis of fine chemicals and
fuels, which has a large impact on energy and environmental research for the
years to come. Diversity in mesoporous frameworks and their potential
applications related to light harvesting, generation of renewable energy and
synthesis of value added fine chemicals and fuels through environment friendly
routes are mostly focused in this review.
PMID- 29962058
TI - Cryosurvival and pregnancy rates: One-step protocol for freezing-thawing Shangri
la Yak (Bos grunniens) Embryos.
AB - The yak is one of the most important and economically useful animals for
highlanders. The decline in the yak population requires effective measures for
the conservation and multiplication of elite germplasm. A standardized protocol
will simplify the freezing and warming of yak embryos in straw and facilitate
embryo transfer. In this work, we investigated a one-step protocol that uses a
stable basal medium, which comprised a warming medium (1.08 M sucrose) and a
freezing medium (EFS40). We also assessed the effects of the new transfer method
on embryo survival. A total of 145 yak frozen embryos were thawed in a standard
medium system. The one-step protocol led to a high recovery percentage (84.93) of
yak embryos that survived vitrification and warming. The in vitro survival rates
of these embryos significantly different from those of embryos frozen-thawed via
the conventional method. The 95 embryos frozen-thawed via our one-step protocol
were then implanted in selected recipients. Thirty-six singleton pregnancies were
established. In conclusion, the proposed one-step method is a simple, safe, and
standardized freezing-thawing protocol that ensures embryo survival and quality
under field conditions. This study establishes new possibilities for the
widespread use of embryo transfer in yaks.
PMID- 29962059
TI - Measuring the interference of pain on daily life in persons with spinal cord
injury: A Rasch-validated subset of items from the Brief Pain Inventory
interference scale.
AB - BACKGROUND/AIM: Up to 60% of individuals report chronic pain after traumatic
spinal cord injury (SCI). Measurement of the degree to which pain interferes with
activities and emotions can provide valuable clinical insights with implications
for pain management interventions. One questionnaire that can be used to quantify
the impact of pain is the Brief Pain Inventory (BPI) interference scale, a seven
item self-report assessment. Our objective was to examine the Rasch measurement
properties of the BPI interference scale for measuring pain interference in
persons with SCI. METHODS: A secondary analysis of cross-sectional, population
based, self-report data was conducted. Participants were adults with traumatic
SCI with residual effects who were at least one year post-injury and 18 years of
age (n = 876). Rasch analysis was used to evaluate the measurement properties of
the BPI interference items for persons with SCI. RESULTS: Two BPI interference
scale items were excluded from analysis due to high rates of missing data. Of the
remaining five items, four items demonstrated acceptable measurement properties
in the SCI population. CONCLUSION: Four of the original seven BPI interference
items provide acceptable measurements of pain interference in the SCI population.
PMID- 29962061
TI - Medication-based versus target-based lipid management.
PMID- 29962060
TI - Establishment of the Alabama Hereditary Cancer Cohort - strategies for the
inclusion of underrepresented populations in cancer genetics research.
AB - BACKGROUND: Historically, groups that are most susceptible to health and
healthcare disparities have been underrepresented in medical research. It is
imperative to explore approaches that can facilitate the recruitment of
underrepresented individuals into research studies. METHODS: Two approaches,
hospital and community-based recruitment (CBR), were developed and implemented
over 36 months to study the genetics of hereditary breast cancer and associated
cancers in Alabama, a medically underserved state with double the national
percentage of self-identifying African Americans, establishing the Alabama
Hereditary Cancer Cohort. RESULTS: Overall, 242 individuals enrolled. This
included 84 cancer probands through hospital recruitment, as well as 76 probands
and 82 family members through CBR. Eighty-one percent of the study participants'
counties of residence are completely medically underserved. Furthermore, African
Americans represent 26% of the hospital probands compared to 49% and 70% of the
probands and family members who, respectively, enrolled through CBR. CONCLUSION:
Although both recruitment mechanisms were instrumental, the unique trust
building, educational, and traveling components of CBR facilitated the enrollment
of African Americans resulting in large families for genetic analyses. The
ultimate goal is to gain insight from these rudimentary efforts in order to
expand recruitment and accrue a unique resource for cancer genetics research.
PMID- 29962062
TI - Anogenital warts in children: Analysis of a cohort of 34 prepubertal children.
AB - Anogenital warts are caused by infection with the human papillomavirus. We
reviewed the clinical data of 34 children younger than 13 with anogenital warts
referred to the department of dermatovenereology of a tertiary care hospital.
Suspicion of sexual abuse was raised in 11 (32.4%). Human papilloma virus testing
and genotyping was performed in 19 (55.9%) children, and human papilloma virus
type 16 was found in 4, which raises the question regarding what type of follow
up is required for children infected with high-risk oncogenic HPV types. Although
the diagnosis of anogenital warts in children raises concerns regarding sexual
abuse, our study supports that pediatric anogenital warts can be associated with
nonsexual transmission.
PMID- 29962063
TI - Intramolecular Natural Energy Decomposition Analysis: Applications to the
Rational Design of Foldamers.
AB - We describe an intramolecular version of the natural energy decomposition
analysis (NEDA), with the aim of evaluating interactions between molecular
fragments across covalent bonds. The electronic energy in intramolecular natural
energy decomposition analysis (INEDA) is divided into electrical, core, and
charge transfer components. The INEDA method describes the fragments using the
nonfragmented electronic density, and, therefore, there are no limitations in how
to choose the boundary orbital. We used INEDA to evaluate the interaction
energies that give origin to barriers of rotation around Camide ?Caromatic (Cam
?Car ) and Namide ?Caromtaic (Nam ?Car ) bonds in arylamide-foldamer building
blocks. We found that differences of barrier height between models with different
ortho-aryl substituents stem from charge transfer and core interactions. In three
center hydrogen-bond (H-bond) models with an NH proton donor H-bound to two
electronegative ortho-aryl substituents, the interaction energy of the three
center system is larger than in either of the two-center H-bond subsystem alone,
indicating an increase of overall rigidity. The combination of INEDA and NEDA
allows the evaluation of intermolecular and intramolecular interactions using a
consistent theoretical framework. (c) 2018 Wiley Periodicals, Inc.
PMID- 29962064
TI - Pediatric tracheomalacia and the perioperative anesthetic management of
thoracoscopic posterior tracheopexy.
AB - Tracheomalacia is a broad term used to describe an abnormally compliant trachea
that can lead to exaggerated collapse and obstruction with expiration. We
describe the perioperative management of a complex pediatric patient undergoing a
posterior tracheopexy which is a relatively new surgical treatment, with a novel
surgical approach-thoracoscopy. This procedure has competing surgical and
anesthetic needs and presents unique challenges to the physicians involved in
caring for these patients. We also review the current literature on pediatric
tracheomalacia and examine the newest treatment options to highlight the
potential anesthetic challenges and pitfalls associated with management.
PMID- 29962066
TI - Surfactant Assembly within Pickering Emulsion Droplets for Fabrication of
Interior-Structured Mesoporous Carbon Microspheres.
AB - Large-sized carbon spheres with controllable interior architecture are highly
desired, but there is no method to synthesize these materials. Here, we develop a
novel method to synthesize interior-structured mesoporous carbon microspheres
(MCMs), based on the surfactant assembly within water droplet-confined spaces.
Our approach is shown to access a library of unprecedented MCMs such as hollow
MCMs, multi-chambered MCMs, bijel-structured MCMs, multi-cored MCMs, "solid"
MCMs, and honeycombed MCMs. These novel structures, unattainable for the
conventional bulk synthesis even at the same conditions, suggest an intriguing
effect arising from the droplet-confined spaces. This synthesis method and the
hitherto unfound impact of the droplet-confined spaces on the microstructural
evolution open up new horizons in exploring novel materials for innovative
applications.
PMID- 29962065
TI - Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating
Oxygenation.
AB - This study uses a highly fidelity computational simulator of pulmonary physiology
to evaluate the impact of a soluble guanylate cyclase (sGC) modulator on gas
exchange in patients with chronic obstructive pulmonary disease (COPD) and
pulmonary hypertension (PH) as a complication. Three virtual patients with COPD
were configured in the simulator based on clinical data. In agreement with
previous clinical studies, modeling systemic application of an sGC modulator
results in reduced partial pressure of oxygen (PaO2 ) and increased partial
pressure of carbon dioxide (PaCO2 ) in arterial blood, if a drug-induced
reduction of pulmonary vascular resistance (PVR) equal to that observed
experimentally is assumed. In contrast, for administration via dry powder
inhalation (DPI), our simulations suggest that the treatment results in no
deterioration in oxygenation. For patients under exercise, DPI administration
lowers PH, whereas oxygenation is improved with respect to baseline values.
PMID- 29962067
TI - Dermoscopic features of idiopathic facial aseptic granuloma.
AB - Idiopathic facial aseptic granuloma is a recently described condition with
defined clinical features, natural history, and underlying histopathologic
findings. Several reports have recently described the potential diagnostic
usefulness of ultrasound findings in idiopathic facial aseptic granuloma. We
describe herein the dermoscopic features of idiopathic facial aseptic granuloma.
PMID- 29962068
TI - Isolation and molecular characterization of Frankia strains resistant to some
heavy metals.
AB - Frankia strains isolated from Saudi Arabia, reported for the first time, were
identified based on the morphological and molecular tools compared to those
isolated from Egypt. All strains displayed typical morphological characterization
of Frankia strains represented by branched hyphae, production of vesicles and
sporangia. The phylogenetic analysis and relationships among Frankia strains were
investigated by comparing 16S rRNA gene sequences. The analysis revealed three
genetic groups which formed two clusters. The first cluster was composed of eight
Frankia strains subdivided into two genetic groups (one group containing five
strains; CgIT3 L2 , CgIS3 N2 , CgIS1 N1, CgIT7N2, and G5; the other group
included of three strains: CgIT5L3, CgIS1 N2 , and CcI13). The second cluster was
composed of only one genetic group of Frankia strain CgIS3 N1 . The strains in
each genetic group exhibited similar genetic distances. All Frankia strains were
able to reinfect their host of Casuarina species. For ability of these strains to
resist heavy metals, our results proved that all Frankia strains isolated can
resist Cu, Co, and Zn at low concentration except Pb which exhibit highly toxic
effect at the same concentration used. Frankia strain G5 was proved to be the
most resistant strain for heavy metals tested.
PMID- 29962069
TI - Limited health literacy and adverse outcomes among kidney transplant candidates.
AB - More than one-third of US adults have limited health literacy, putting them at
risk of adverse clinical outcomes. We evaluated the prevalence of limited health
literacy among 1578 adult kidney transplant (KT) candidates (May 2014-November
2017) and examined its association with listing for transplant and waitlist
mortality in this pilot study. Limited health literacy was assessed at KT
evaluation by using a standard cutoff score <=5 on the Brief Health Literacy
Screen (score range 0-12, lower scores indicate worse health literacy). We used
logistic regression and adjusted Cox proportional hazards models to identify risk
factors for limited health literacy and to quantify its association with listing
and waitlist mortality. We found that 8.9% of candidates had limited health
literacy; risk factors included less than college education (adjusted odds ratio
[aOR] = 2.87, 95% confidence interval [CI]:1.86-4.43), frailty (aOR = 1.85, 95%
CI:1.22-2.80), comorbidity (Charlson comorbidity index [1-point increase] aOR =
1.12, 95% CI: 1.04-1.20), and cognitive impairment (aOR = 3.45, 95% CI: 2.20
5.41) after adjusting for age, sex, race, and income. Candidates with limited
health literacy had a 30% (adjusted hazard ratio = 0.70, 95% CI: 0.54-0.91)
decreased likelihood of listing and a 2.42-fold (95% CI: 1.16- to 5.05-fold)
increased risk of waitlist mortality. Limited health literacy may be a salient
mechanism in access to KT; programs to aid candidates with limited health
literacy may improve outcomes and reduce disparities.
PMID- 29962070
TI - Default-mode network dynamics are restricted during high speed discrimination in
healthy aging: Associations with neurocognitive status and simulated driving
behavior.
AB - Numerous daily tasks, including car driving, require fine visuospatial tuning.
One such visuospatial ability, speed discrimination, declines with aging but its
neural underpinnings remain unknown. In this study, we use fMRI to explore the
effect of aging during a high speed discrimination task and its neural
underpinnings, along with a complete neuropsychological assessment and a
simulated driving evaluation in order to examine how they interact with each
other through a multivariate regression approach. Beyond confirming that high
speed discrimination performance is diminished in the elderly, we found that this
deficit might be partly due to a lack of modulation in the activity and
connectivity of the default mode network (DMN) in this age group, as well as an
over-recruitment of frontoparietal and cerebellar regions, possibly as a
compensatory mechanism. In addition, younger adults tended to drive at faster
speeds, a behavior that was associated to adequate DMN dynamics and executive
functioning, an effect that seems to be lost in the elderly. In summary, these
results reveal how age-related declines in fine visuospatial abilities, such as
high speed discrimination, were distinctly mediated by DMN functioning, a
mechanism also associated to speeding behavior in a driving simulator.
PMID- 29962071
TI - Pt-M Complexes (M=Ag, Au) as Models for Intermediates in Transmetalation
Processes.
AB - Heteropolynuclear complexes [(CNC)(PPh3 )PtM(PPh3 )]ClO4 [M=Au (1), Ag (2)] and
[{Pt(CNC)(PPh3 )}2 M]ClO4 [M=Ag (3), Au (4); CNC=2,6-diphenylpyridinate] were
prepared and studied by X-ray crystallography, spectroscopic techniques, and DFT
calculations. The X-ray crystal structures of 1, 3, and 4 confirmed the existence
of Pt-M bonds and M???Cipso interactions involving one of the phenyl fragments of
CNC. Their NMR spectra showed the persistence of the Pt-M interactions in
solution and also revealed an intramolecular metronome-like dynamic process
consisting of back-and-forth motion of the acidic M fragments along the C-Pt-C
axis. DFT calculations on these complexes identified two main orbital
interactions between the [PtCNC] and [M]+ fragments, namely, donation from the
former to a vacant orbital of the latter and much weaker backdonation from the
acidic M to the Pt fragment. Overall, the strength of the [Pt]???M interactions
is higher for the gold compounds than for their silver counterparts. The
interaction between the acidic center (silver or gold) and the carbon atom of one
of the phenylene rings in these heteropolymetallic complexes can be envisaged as
the first step in a process of interchange of aryl ligands. However, the ligand
exchange cannot progress further due to the polydentate nature of the CNC ligand,
and therefore these structures can be considered as frozen snapshots of a
transmetalation reaction that has been arrested at different stages of the
process.
PMID- 29962072
TI - Materials Nanoarchitectonics Using 2D Layered Materials: Recent Developments in
the Intercalation Process.
AB - Layered inorganic solids as an attractive classification of 2D materials offer
material diversity and a wide range of interesting properties. Layered inorganic
solids provide an expandable 2D nanospace between each individual layer, the so
called interlayer space, to accommodate/arrange guest species such as molecules,
nanoparticles, and polymer chains and design unique nanoarchitectures, resulting
in the production of intercalation compounds showing different properties in
comparison to those of virgin layered materials and guest species. Layered
inorganic solids can also be exfoliated to result in nanosheet production.
Further ordering of exfoliated nanosheets is also possible via different methods
and normally leads to creating soft materials presenting properties and
applications different from that of relatively rigid intercalation compounds.
Here, the latest studies and up-to-date developments on the possible techniques
of designing novel types of materials using layered inorganic solids are
specifically highlighted.
PMID- 29962073
TI - Cardiac shock wave therapy improves myocardial perfusion and preserves left
ventricular mechanics in patients with refractory angina: A study with speckle
tracking echocardiography.
AB - BACKGROUND: Cardiac shockwave therapy (CSWT) is a new potential option for the
treatment of patients with chronic coronary disease and refractory angina (RA).
We aimed to study the effects of CSWT on left ventricular myocardial perfusion
and mechanics in patients with RA. METHOD: We prospectively studied 19 patients
who underwent CSWT. Left ventricular mechanics were evaluated by speckle tracking
echocardiography (STE), and myocardial perfusion by single-photon emission
computed tomography, using stress/rest-Technetium-99 m Sestamibi, for
determination of summed stress score (SSS). Canadian Cardiac Society (CCS), New
York Heart Association (NYHA), and quality of life by Seattle Angina
Questionnaire (SAQ) were assessed at baseline and 6 months after therapy.
RESULTS: CSWT therapy was applied without major side effects. At baseline, 18
patients (94.7%) had CCS class III or IV, and after CSWT there was reduction to 3
(15.8%), P = .0001, associated with improvement in SAQ (38.5%; P < .001).
Thirteen (68.4%) had class NYHA III or IV before treatment, with significant
reduction to 7 (36.8%); P = .014. No change was observed in the global SSS from
baseline to 6-month follow-up (15.33 +/- 8.60 vs 16.60 +/- 8.06; P = .157).
However, there was a significant reduction in the average SSS of the treated
ischemic segments (2.1 +/- 0.87 pre vs 1.6 +/- 1.19 post CSWT; P = .024). Global
longitudinal strain by STE remained unaltered (-13.03 +/- 8.96 pre vs -15.88 +/-
3.43 6-month post CSWT; P = .256). CONCLUSION: CSWT is a safe procedure for the
treatment of patients with RA that results in better quality of life, improvement
in myocardial perfusion of the treated segments with preservation of left
ventricular mechanics.
PMID- 29962074
TI - What and when is diabetes? A devil's advocate perspective on contemporary
controversies in diabetes criteria and classification.
PMID- 29962075
TI - Fluorinated antimicrobial lysine-based peptidomimetics with activity against
methicillin-resistant Staphylococcus pseudintermedius.
AB - Staphylococcus pseudintermedius is the predominant opportunistic pathogen in dogs
causing primarily integumentary infections such as pyoderma and otitis. The
worldwide emergence of methicillin-resistant S. pseudintermedius (MRSP)
constitutes a significant health problem for companion animals in veterinary
medicine. Thus, discovery of novel agents for treatment of MRSP-associated
infections is highly warranted. In the present work, structure-activity
relationships (based on testing of 37 peptidomimetics) have been explored with
the aim of determining the influence of oligomer length as well as effect of
fluorination, end-group modification, and length of hydrophobic side chains.
Incorporation of fluorine atoms and elongation of hydrophobic side chains both
conferred overall increased potency without significantly enhancing the hemolytic
properties of the compounds. Importantly, it was found that when targeting MRSP,
the peptidomimetic length could be reduced from 12 to 8 residues without
substantial loss of antibacterial activity. By contrast, introduction of end
group modifications did not improve the activity against MRSP (10 strains
tested), but conferred increased activity against Staphylococcus aureus,
Escherichia coli, and Pseudomonas aeruginosa, albeit the concomitantly increased
hemolytic properties resulted in a slightly lowered cell selectivity.
PMID- 29962076
TI - Pifithrin-MU modulates microglial activation and promotes histological recovery
following spinal cord injury.
AB - BACKGROUND: Treatments immediately after spinal cord injury (SCI) are anticipated
to decrease neuronal death, disruption of neuronal connections, demyelination,
and inflammation, and to improve repair and functional recovery. Currently,
little can be done to modify the acute phase, which extends to the first 48 hours
post-injury. Efforts to intervene have focused on the subsequent phases -
secondary (days to weeks) and chronic (months to years) - to both promote
healing, prevent further damage, and support patients suffering from SCI.
METHODS: We used a contusion model of SCI in female mice, and delivered a small
molecule reagent during the early phase of injury. Histological and behavioral
outcomes were assessed and compared. RESULTS: We find that the reagent Pifithrin
MU (PFT-MU) acts early and directly on microglia in vitro, attenuating their
activation. When administered during the acute phase of SCI, PFT-MU resulted in
reduced lesion size during the initial inflammatory phase, and reduced the
numbers of pro-inflammatory microglia and macrophages. Treatment with PFT-MU
during the early stage of injury maintained a stable anti-inflammatory
environment. CONCLUSIONS: Our results indicate that a small molecule reagent PFT
MU has sustained immunomodulatory effects following a single dose after injury.
PMID- 29962077
TI - Boron Ester-Catalyzed Amidation of Carboxylic Acids with Amines: Mechanistic
Rationale by Computational Study.
AB - A novel boron ester-catalyzed amidation reaction of carboxylic acids and amines
with unprecedented functional group tolerance was recently reported. To gain
deeper insights into this reaction, a computational study with density functional
theory methods was performed in this manuscript. Calculations indicate that the
amidation starts with the condensation of carboxylic acids with the boron ester
catalyst. The resulting monoacyloxylated boron species further undergoes the
carboxylic acid-assisted nucleophilic addition with amines to generate the amide
product and a monohydroxyboron species. The condensation of the carboxylic acid
with the monohydroxyboron species with the assistance of an amine regenerates
monoacyloxylated boron species to finish the catalytic cycle. The rate
determining step is catalyst regeneration and the amine-coordinated
monohydroxyboron species is the resting state in the catalytic cycle. The present
results are consistent with the previous NMR study and the observed reaction
orders of catalyst and substrates; it is expected to benefit further reaction
optimization.
PMID- 29962078
TI - Nucleophile-initiated Catalytic and Multicomponent Reactions.
AB - A number of well-known reactions, proceed through the intermediacy of
dipolar/zwitterionic species generated via the addition of a neutral nucleophile
with an unsaturated electrophile. A mechanistic understanding of these reactions
was made possible by seminal contributions of Huisgen. The design of novel
reactions based on such dipolar species was, however, not pursued in detail for a
long time. Our efforts to exploit various reactivity profiles available for the
zwitterionic/dipolar intermediates have resulted in the discovery of a large
number of novel, convenient protocols to access a wide variety of products. The
nucleophilic initiators may participate in the reaction or play a mediating role
depending upon the nature of nucleophile, its quantity and the reaction
conditions. In a majority of these transformations two electrophilic components,
that would normally be inert towards each other, are combined by the intermediacy
of a nucelophile. A brief summary of such nucleophile-initiated novel reactions
that were developed in our research group are described. Reactions involving a
variety of nucleophiles such as phosphines, pyridine, quinoline, isoquinoline,
isocyanides, dimethoxycarbene and N-heterocyclic carbenes (NHCs) are discussed.
PMID- 29962079
TI - Kinetics of the Same Reaction Monitored over Nine Orders of Magnitude in
Concentration: When Are Unique Subensemble and Single-Turnover Reactivity
Displayed?
AB - Essentially no information is known about the behavior of individual molecular
catalysts under reaction conditions. This is a result of the averaging inherent
to traditional analytical techniques. Herein, a combined fluorescence microscopy
and 1 H NMR spectroscopy study reveals that unique (that is, non-ensemble
averaged) distributions and time-variable kinetics from molecular ruthenium
catalysts within growing polynorbornene occur and are detectable between 10-9 m
and 10-6 m of substrate, surprisingly just 1000-fold less concentrated than a
typical laboratory bench-scale reaction. The kinetic states governing single
turnover events are determinable by overlay of the signal arising from individual
monomer insertion reactions with that from polymer growth from neighboring
catalysts.
PMID- 29962080
TI - Successful management of recurrent focal segmental glomerulosclerosis.
AB - Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients
after kidney transplantation. Herein we report the successful management of
recurrent FSGS. A 5-year-old boy with primary FSGS received a deceased donor
renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft
failure that was resistant to plasmapheresis and rituximab. After exclusion of
structural or immunologic damage to the kidney by repeated biopsies, the
allograft was retrieved from the first recipient on day 27 and transplanted into
a 52-year-old second recipient who had vascular nephropathy. Immediately after
retransplantation, the allograft regained function with excellent graft function
persistent now at 3 years after transplant. After 2 years on hemodialysis, the
boy was listed for kidney retransplantation. To prevent FSGS recurrence,
pretreatment with ofatumumab was performed. Nephrotic range proteinuria still
occurred after the second transplantation, which responded, however, to daily
plasma exchange in combination with ofatumumab. At 8 months after kidney
retransplantation graft function is good. The clinical course supports the
hypothesis of a circulating permeability factor in the pathogenesis of FSGS.
Successful ofatumumab pretreatment implicates a key role of B cells. Herein we
provide a description of successful management of kidney failure by FSGS,
carefully avoiding waste of organs.
PMID- 29962081
TI - Identification of an HLA-A null allele, HLA-A*33:129N.
AB - HLA-A*33:129N has a single nucleotide insertion compared with its closest allele
HLA-A*33:01:01 at codon 186.
PMID- 29962082
TI - Abnormalities in thrombotic pathways in diabetes: A tale of two platelets.
PMID- 29962083
TI - Immobilization of Photo-Immunoconjugates on Nanoparticles Leads to Enhanced Light
Activated Biological Effects.
AB - The past three decades have witnessed notable advances in establishing
photosensitizer-antibody photo-immunoconjugates for photo-immunotherapy and
imaging of tumors. Photo-immunotherapy minimizes damage to surrounding healthy
tissue when using a cancer-selective photo-immunoconjugate, but requires a
threshold intracellular photosensitizer concentration to be effective. Delivery
of immunoconjugates to the target cells is often hindered by I) the low
photosensitizer-to-antibody ratio of photo-immunoconjugates and II) the limited
amount of target molecule presented on the cell surface. Here, a nanoengineering
approach is introduced to overcome these obstacles and improve the effectiveness
of photo-immunotherapy and imaging. Click chemistry coupling of benzoporphyrin
derivative (BPD)-Cetuximab photo-immunoconjugates onto FKR560 dye-containing
poly(lactic-co-glycolic acid) nanoparticles markedly enhances intracellular photo
immunoconjugate accumulation and potentiates light-activated photo-immunotoxicity
in ovarian cancer and glioblastoma. It is further demonstrated that co-delivery
and light activation of BPD and FKR560 allow longitudinal fluorescence tracking
of photoimmunoconjugate and nanoparticle in cells. Using xenograft mouse models
of epithelial ovarian cancer, intravenous injection of photo-immunoconjugated
nanoparticles doubles intratumoral accumulation of photo-immunoconjugates,
resulting in an enhanced photoimmunotherapy-mediated tumor volume reduction,
compared to "standard" immunoconjugates. This generalizable "carrier effect"
phenomenon is attributed to the successful incorporation of photo
immunoconjugates onto a nanoplatform, which modulates immunoconjugate delivery
and improves treatment outcomes.
PMID- 29962084
TI - Agricultural land use creates evolutionary traps for nesting turtles and is
exacerbated by mercury pollution.
AB - The rate of anthropogenic habitat conversion often exceeds the rate of natural
ecological and evolutionary processes, which sometimes creates mismatches between
environmental cues and adaptive behaviors. In numerous species of aquatic
turtles, nest site selection is primarily based on cues related to high solar
exposure, which leads females to select sites where humans have disturbed
habitat. These disturbed sites are often contaminated by pollutants, such as
mercury. Despite the fact that anthropogenic disturbances often co-occur, few
studies have examined the interactive influence of major global changes on animal
development. Using Chelydra serpentina, we investigated the individual and
interactive effects of crop agriculture and mercury pollution on hatch success
and offspring phenotype. We hypothesized that following nesting, rapid crop
growth would shade and cool nests in agricultural fields and subsequently
negatively impact embryonic development. Agricultural and control nests were
similar in temperature at the time of oviposition, but temperatures diverged as
crops grew: agricultural nests averaged 2.5 degrees C cooler than control nests
over the course of incubation. In laboratory and field experiments, we found that
turtles incubated under agricultural thermal regimens took longer to hatch,
hatched at smaller body sizes, lost more mass, and had lower posthatching growth
rates. Additionally, thermal conditions associated with agricultural land use
interacted with mercury contamination to decrease hatching success. To our
knowledge, this is the first documentation of negative interactive effects of
mercury pollution and habitat quality on early vertebrate development and
highlights the importance of examining the combined influence of anthropogenic
global changes on organisms.
PMID- 29962085
TI - Metabolic syndrome emerges after artificial selection for low baroreflex
sensitivity.
AB - AIMS: It is unclear whether the impaired BRS plays a key role in the incidence of
cardiovascular diseases. The molecular mechanism of impaired BRS remains to be
fully elucidated. We hypothesized that selection of rats based on deficient and
normal intrinsic BRS would yield models that reflect cardiovascular diseases
risk. METHODS AND RESULTS: Twenty generations of selection produced arterial
baroreflex low rats and normal rats that differed in BRS by about 2.5-fold
change. Metabolic syndrome (including hypertension, overweight, hyperlipemia, and
hyperglycemia) emerged in ABR-DRs. Although ABR-DRs consumed less food, they
gained significantly more body weight. CONCLUSION: Our study demonstrated that
intrinsic low BRS induced hypertension and metabolic disorder. Restoration of
impaired BRS might be a potent target of therapeutic intervention in metabolic
syndrome.
PMID- 29962086
TI - Potential of cassava clones enriched with beta-carotene and lycopene for zinc
biofortification under different soil Zn conditions.
AB - BACKGROUND: Zinc (Zn) deficiency is a major human health concern worldwide, and
biofortification (genetic and agronomic) is a complementary solution for
increasing micronutrient contents, including Zn. Cassava (Manihot esculenta
Crantz) has been used for Zn biofortification because it is an important staple
crop in most countries affected by malnutrition and Zn deficiency. Thus studies
on biofortification of this crop can improve its nutritional quality. Zn content
in cassava clones enriched with beta-carotene or lycopene and cultivated under
different areas and soil managements was investigated to evaluate the influence
of genotypic variation and agronomic management on Zn status in the plant.
RESULTS: A clone-specific response to total Zn content in the soil was found,
with clones 26, 215, and 240 (beta-carotene enriched) and clones 341 and 395
(lycopene enriched) being the most responsive. For both experiments, there was a
positive interaction between total soil Zn and Zn content in the roots.
CONCLUSIONS: Our results suggest that, by combining plant breeding and agronomic
strategies, it is possible to enrich cassava roots with both zinc and beta
carotene or lycopene. (c) 2018 Society of Chemical Industry.
PMID- 29962087
TI - Management of large ureteral stone with severe ureteral tortuosity: A novel
technique of "straightening" against the tortuous ureter using simultaneous
supine percutaneous nephrolithotomy and retrograde semirigid ureterolithotripsy.
PMID- 29962088
TI - Antimetastatic effects of Eclipta prostrata extract on oral cancer cells.
AB - Eclipta prostrata, a traditional Chinese medication, has been used for the
treatment of several diseases. However, the molecular mechanism underlying the
effects of Eclipta prostrata extracts (EPE) on human oral cancer cell metastasis
remains unclear. We thus examined the effects of EPE on metastasis promoting
proteins in oral cancer. Our results revealed that the EPE attenuated SCC-9, HSC
3, and TW2.6 cell migration and invasiveness by reducing matrix metalloproteinase
(MMP)-2 enzyme activities. In addition, Western blot analysis revealed that EPE
significantly reduced the levels of phosphorylated extracellular signal-regulated
kinase 1/2 (ERK 1/2) but not those of c-Jun N-terminal kinase (JNK) 1/2 and p38.
In conclusion, we found that EPE could inhibit oral cancer metastasis through the
inhibition of MMP-2 expression. Therefore, EPE may be used to prevent the
metastasis of oral cancer, and has the potential to be applied to cancer
treatment.
PMID- 29962090
TI - Pilot evaluation of a web-based acceptance and commitment therapy program to
promote mental health skills in university students.
AB - OBJECTIVE: This study evaluated a 4-week web-based acceptance and commitment
therapy (ACT) mental health promotion program called YOLO (You Only Live Once)
for university students. METHOD: A total of 130 participants were randomized to
one of three intervention groups investigating varied program delivery methods.
Primary outcomes assessed: depression, anxiety, stress, well-being, self
compassion, alcohol use, and life satisfaction. ACT processes assessed:
acceptance, cognitive fusion, education values, valued living, and mindfulness.
RESULTS: Improvement on the primary outcomes and ACT processes did not differ
among the three intervention groups. Analyses showed significant improvements on
all primary outcomes (except alcohol use), and on all ACT processes. All ACT
processes mediated changes on one or more primary outcomes in the intent-to-treat
sample. Intervention effects were consistent on most primary outcomes and ACT
processes across three sample groupings. CONCLUSIONS: These preliminary findings
provide support for a web-based ACT mental health promotion program for
university students.
PMID- 29962089
TI - Impact of liver PGC-1alpha on exercise and exercise training-induced regulation
of hepatic autophagy and mitophagy in mice on HFF.
AB - Hepatic autophagy has been shown to be regulated by acute exercise and exercise
training. Moreover, high-fat diet-induced steatosis has been reported to be
associated with impaired hepatic autophagy. In addition, autophagy has been shown
to be regulated by acute exercise and exercise training in a PGC-1alpha dependent
manner in skeletal muscle. The aim of this study was to test the hypotheses that
high-fat high-fructose (HFF) diet changes hepatic autophagy and mitophagy, that
exercise training can restore this through a PGC-1alpha-mediated mechanism, and
that acute exercise regulates autophagy and mitophagy in the liver. Liver samples
were obtained from liver-specific PGC-1alpha KO mice and their littermate Lox/Lox
mice fed a HFF diet or a control diet for 13 weeks. The HFF mice were either
exercise trained (ExT) on a treadmill the final 5 weeks or remained sedentary
(UT). In addition, half of each group performed at the end of the intervention an
acute 1 h exercise bout. HFF resulted in increased hepatic BNIP3 dimer and Parkin
protein, while exercise training increased BNIP3 total protein without affecting
the elevated BNIP3 dimer protein. In addition, exercise training reversed a HFF
induced increase in hepatic LC3II/LC3I protein ratio, as well as a decreased PGC
1alpha mRNA level. Acute exercise increased hepatic PGC-1alpha mRNA in HFF UT
mice only. In conclusion, this indicates that exercise training in part reverses
a HFF-induced increase in hepatic autophagy and capacity for mitophagy in a PGC
1alpha-independent manner. Moreover, HFF may blunt acute exercise-induced
regulation of hepatic autophagy.
PMID- 29962091
TI - Fluoride intake and cortical and trabecular bone characteristics in adolescents
at age 17: A prospective cohort study.
AB - OBJECTIVE: To investigate the associations between period-specific and cumulative
fluoride (F) intakes from birth to age 17 years, and radial and tibial bone
measures obtained using peripheral quantitative computed tomography (pQCT).
METHODS: Participants (n = 380) were recruited from hospitals at birth and
continued their participation in the ongoing Iowa Fluoride Study/Iowa Bone
Development Study until age 17. Fluoride intakes from water, other beverages,
selected foods, dietary fluoride supplements and dentifrice were determined every
1.5-6 months using detailed questionnaires. Associations between F intake and
bone measures (cortical and trabecular bone mineral content [BMC], density and
strength) were determined in bivariate and multivariable analyses adjusted for
height, weight, maturity offset, physical activity, and daily calcium and protein
intake using robust regression analysis. RESULTS: Fluoride intake ranged from 0.7
to 0.8 mg F/d for females and from 0.7 to 0.9 mg F/d for males. Spearman
correlations between daily F intake and pQCT bone measures were weak. For
females, Spearman correlations ranged from r = -.08 to .21, and for males, they
ranged from r = -.03 to .30. In sex-specific, height-, weight- and maturity
offset- partially adjusted regression analyses, associations between females'
fluoride intake and bone characteristics were almost all negative; associations
for males were mostly positive. In the fully adjusted models, which also included
physical activity, and protein and calcium intakes, no significant associations
were detected for females; significant positive associations were detected
between F intake from 14 to 17 years and tibial cortical bone content (beta =
21.40, P < .01) and torsion strength (beta = 175.06, P < .01) for males.
CONCLUSION: In this cohort of 17-year-old adolescents, mostly living in optimally
fluoridated areas, lifelong F intake from combined sources was weakly associated
with bone pQCT measures.
PMID- 29962092
TI - Sinus of valsalva aneurysm associated with a left main coronary artery
dissection.
PMID- 29962093
TI - MicroRNA-137-mediated Src oncogenic signaling promotes cancer progression.
AB - The tyrosine kinase c-Src is frequently overexpressed and activated in a wide
variety of human cancers. However, the molecular mechanisms responsible for the
upregulation of c-Src remain elusive. To examine whether microRNA-mediated c-Src
upregulation promotes cancer progression, we screened miRNAs with complementarity
to the 3'-UTR of c-Src mRNA. Among these miRNAs, down-regulation of miR-137 was
tightly associated with c-Src-mediated tumor progression of human colon cancer
cells/tissues. Re-expression of miR-137 in human colon cancer cells suppressed
tumor growth and caused the disruption of focal contacts, suppression of cell
adhesion, and invasion, although restoration of c-Src in miR-137-treated cells
could not fully rescue the tumor-suppressive effect of miR-137. We found that miR
137 targets AKT2 and paxillin also and miR-137-mediated regulation of c-Src /AKT2
is crucial for controlling tumor growth, whereas that of c-Src/paxillin
contributes to malignancy. miR-137 suppressed Src-related oncogenic signaling and
changed the expression of miRNAs that are regulated by Src activation. miR-137
controls the expression of c-Src/AKT2/paxillin and synergistically suppresses Src
oncogenic signaling evoked from focal adhesions. In various human cancers that
harbor c-Src upregulation, the dysfunction of this novel mechanism would serve as
a critical trigger for tumor progression.
PMID- 29962094
TI - Egg cannibalism in capelin Mallotus villosus at beach and deep-water spawning
habitats in the north-west Atlantic Ocean.
AB - We investigated egg cannibalism in spawning capelin Mallotus villosus on the
north-east Newfoundland coast during July 2012-2014, specifically whether sex,
spawning condition (i.e., spawning or spent) and spawning habitat influenced egg
cannibalism. Capelin spawning in deep-water were 4.5-14 times more likely to be
cannibals than those at the beach, probably due to the higher spatial overlap of
spawners and conspecific eggs within this habitat relative to beaches. Males were
2.1-3.7 times more likely to be cannibals than females, but female cannibals had
more eggs per stomach. Spawning fish were 1.6-1.9 times more likely to be
cannibals than spent fish, but spent female cannibals had more eggs per stomach
relative to spawning males and females in either habitat. Findings suggest that
cannibalism may be an important foraging strategy, especially at deep-water
spawning habitat, possibly extending the spawning season for males or increasing
the probability of post-spawning survival for females. Although 44% of sampled
females and 50% of males were cannibals, the estimated mortality due to egg
cannibalism was low (0.49-2.97% of eggs produced annually), suggesting that egg
cannibalism does not influence recruitment to a great extent in Newfoundland
capelin.
PMID- 29962095
TI - Can antenatal diet and lifestyle interventions influence childhood obesity? A
systematic review.
AB - Evidence suggests that adverse nutritional exposures during in utero development
may contribute to heightened risk of obesity in childhood. Pregnancy offers the
opportunity to modify the intrauterine environment by manipulation of diet and/or
physical activity, which may result in favourable health benefits for the child.
The objective of this systematic review was to determine whether antenatal
lifestyle interventions in pregnant women, aimed at modifying diet and/or
physical activity, and lead to a reduction in measures of offspring obesity in
early childhood. Three electronic databases were searched from January 1990 to
July 2017 for antenatal interventions with subsequent offspring follow-up
publications. Eight trials were identified. Five trials included women from all
body mass index categories, and 3 trials included obese women only. Children in
the offspring follow-up studies were aged 6 months to 7 years. Measures of
adiposity in the offspring (n = 1989) included weight, body mass index, z-scores,
circumferences, and skinfold thicknesses. Two studies, focusing on obese women
only, reported reduced measures of adiposity (subscapular skinfold thickness and
weight-for-age z-score) at 6 and 12 months, respectively. The remaining 6
studies, two from infancy and 4 in early childhood found no effect on measures of
adiposity. Measures of obesity up to 12 months of age have been shown to be
reduced by antenatal lifestyle interventions during pregnancy in obese women. Due
to the heterogeneity of the methodology of the antenatal interventions and the
reported offspring outcomes we were unable to draw any conclusion on the
influence of antenatal interventions on measures of obesity in early childhood.
PMID- 29962096
TI - The Racovitzan impediment and the hidden biodiversity of unexplored environments.
PMID- 29962097
TI - Childhood pilomatricomas: Associated anomalies.
AB - Pilomatricoma is a common benign tumor in children. We present a review of the
literature with the aim of helping clinicians manage these patients. A detailed
review of the literature was performed in the PubMed database using an exhaustive
list of Medical Subject Heading words. One thousand four hundred fifty-eight
children were described in retrospective series and case reports. An associated
disease was found in 32 children (2.2%), most of whom had several pilomatricomas
(n = 23); 9 had a single lesion. Based on this literature review, we recommend
reassuring the family and then conducting a detailed interview regarding past
medical and family history and a thorough clinical examination for signs of
Turner syndrome, constitutional mismatch repair deficiency, Kabuki syndrome,
Steiner's myotonic dystrophy, or Gardner syndrome. Regular long-term clinical
follow-up is recommended. Specific paraclinical examinations should be performed
only in cases of other clinical anomalies or a positive family history.
Pilomatricoma requires management because it may be associated with other
potentially serious diseases, especially when multiple lesions are present.
PMID- 29962098
TI - Immediate effects of leg-press exercises with tibial internal rotation on
individuals with medial knee osteoarthritis.
AB - OBJECTIVE: Although patients with knee osteoarthritis (OA) demonstrate abnormal
kinematics involving greater tibial external rotation during squatting, there
have not been any previous studies investigating an exercise focused on
correcting knee rotational kinematics. This study aimed to determine the
immediate effects of exercise with tibial internal rotation (IR) on symptoms and
functions in patients with knee osteoarthritis (KOA). METHODS: This study
provides Level II evidence using a small randomized controlled trial. Sixty
patients were allocated to either the tibial IR or neutral rotation (NR) group in
this randomized controlled trial. The IR group performed a leg press activity
with the tibia in maximal IR, whereas the NR group performed leg press activity
with the tibia in NR. Outcome measures were (a) 10-m walk test; (b) Timed Up and
Go test, (c) knee flexion angle while squatting, (d) knee pain during walking and
squatting, and (e) difficulty during walking and squatting. RESULTS: Significant
interaction was observed in all outcomes. The IR group exhibited significant
improvement on all outcome measures, whereas the NR group exhibited significant
improvements only in the 10-m walk. CONCLUSION: The IR group exhibited greater
improvements than the NR group on all outcome measures. After a single session,
leg press activity with the tibia in maximal IR improved the symptoms and
functions measured in this study more effectively than leg press activity with
the tibia in a neutral position. This suggests that correcting rotational
malalignment is more important than strengthening the quadriceps for maintaining
or even improving function of OA knees. (Clinical trials registration number:
UMIN000021751).
PMID- 29962099
TI - Excitation and Amplification of Spin Waves by Spin-Orbit Torque.
AB - The emerging field of nanomagnonics utilizes high-frequency waves of
magnetization-spin waves-for the transmission and processing of information on
the nanoscale. The advent of spin-transfer torque has spurred significant
advances in nanomagnonics, by enabling highly efficient local spin wave
generation in magnonic nanodevices. Furthermore, the recent emergence of spin
orbitronics, which utilizes spin-orbit interaction as the source of spin torque,
has provided a unique ability to exert spin torque over spatially extended areas
of magnonic structures, enabling enhanced spin wave transmission. Here, it is
experimentally demonstrated that these advances can be efficiently combined. The
same spin-orbit torque mechanism is utilized for the generation of propagating
spin waves, and for the long-range enhancement of their propagation, in a single
integrated nanomagnonic device. The demonstrated system exhibits a controllable
directional asymmetry of spin wave emission, which is highly beneficial for
applications in nonreciprocal magnonic logic and neuromorphic computing.
PMID- 29962100
TI - Regulation of hepatic glucose production and AMPK by AICAR but not by metformin
depends on drug uptake through the equilibrative nucleoside transporter 1 (ENT1).
AB - AIM: Recently we have observed differences in the ability of metformin and AICAR
to repress glucose production from hepatocytes using 8CPT-cAMP. Previous results
indicate that, in addition to activating protein kinase A, 8CPT-modified cAMP
analogues suppress the nitrobenzylthioinosine (NBMPR)-sensitive equilibrative
nucleoside transporter ENT1. We aimed to exploit 8CPT-cAMP, 8CPT-2-Methyl-O-cAMP
and NBMPR, which is highly selective for a high-affinity binding-site on ENT1, to
investigate the role of ENT1 in the liver-specific glucose-lowering properties of
AICAR and metformin. METHODS: Primary mouse hepatocytes were incubated with AICAR
and metformin in combination with cAMP analogues, glucagon, forskolin and NBMPR.
Hepatocyte glucose production (HGP) and AMPK signalling were measured, and a
uridine uptake assay with supporting LC-MS was used to investigate nucleoside
depletion from medium by cells. RESULTS: AICAR and metformin increased AMPK
pathway phosphorylation and decreased HGP induced by dibutyryl cAMP and glucagon.
HGP was also induced by 8CPT-cAMP, 8CPT-2-Methyl-O-cAMP and NBMPR; however, in
each case this was resistant to suppression by AICAR but not by metformin. Cross
validation of tracer and mass spectrometry studies indicates that 8CPT-cAMP, 8CPT
2-Methyl-O-cAMP and NBMPR inhibited the effects of AICAR, at least in part, by
impeding its uptake into hepatocytes. CONCLUSIONS: We report for the first time
that suppression of ENT1 induces HGP. ENT1 inhibition also impedes uptake and the
effects of AICAR, but not metformin, on HGP. Further investigation of nucleoside
transport may illuminate a better understanding of how metformin and AICAR each
regulate HGP.
PMID- 29962101
TI - Is it time for a culture change? Blood culture collection in the emergency
department.
AB - OBJECTIVE: To describe how frequently blood cultures (BCs) are obtained in the ED
and to describe the incidence of true- and false-positive BC results. METHODS:
Retrospective descriptive study of all patients presenting to a tertiary-level,
mixed Australian ED over a 15 month period. RESULTS: A total of 3617 (3.67%)
patients had BCs collected. Around one (12.1%) in eight of these BCs were
positive; nearly half (45.2%) of which were identified as a false positive.
CONCLUSIONS: BCs are a common investigation in the ED with a high false-positive
rate. Strategies are required to reduce false positives, including reducing
inappropriate collection and improving collection techniques.
PMID- 29962102
TI - Magnetophoretic Sorting of Single Catalyst Particles.
AB - A better understanding of the deactivation processes taking place within solid
catalysts is vital to design better ones. However, since inter-particle
heterogeneities are more a rule than an exception, particle sorting is crucial to
analyse single catalyst particles in detail. Microfluidics offers new
possibilities to sort catalysts at the single particle level. Herein, we report a
first-of-its-kind 3D printed magnetophoretic chip able to sort catalyst particles
by their magnetic moment. Fluid catalytic cracking (FCC) particles were separated
based on their Fe content. Magnetophoretic sorting shows that large Fe aggregates
exist within 20 % of the FCC particles with the highest Fe content. The
availability of Bronsted acid sites decreases with increasing Fe content. This
work paves the way towards a high-throughput catalyst diagnostics platform to
determine why specific catalyst particles perform better than others.
PMID- 29962104
TI - Seroprevalence of malignant catarrhal fever virus in captive wildebeest
(Connochaetes sp.) in France.
AB - Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus carried asymptomatically
by wildebeests (Connochaetes sp.) in sub-Saharan Africa. Although asymptomatic in
wildebeest, AlHV-1 infection in a number of other ruminant species causes a
severe and fatal lymphoproliferative disease named wildebeest-derived malignant
catarrhal fever (WD-MCF). Several endangered species of captive ruminants are
highly susceptible to developing WD-MCF if infected by AlHV-1, which is a
critical concern in zoos, game reserves and wildlife parks where wildebeests are
also kept in captivity. Here, we investigated the seroprevalence of AlHV-1 in 52
captive wildebeests randomly sampled from five different zoos in France. We found
46% (24/52) seropositive animals and detected AlHV-1 DNA in one of them,
demonstrating that AlHV-1 infection is present in captive wildebeests in France.
In an interesting manner, the repartition of seropositive wildebeests was not
homogenous between zoos with 100% (20/20) of seronegative animals in three parks.
These results further highlight the importance of considering WD-MCF as a threat
for clinically susceptible species and encourage for testing AlHV-1 infection in
captive wildebeests as a management control strategy.
PMID- 29962105
TI - The Impact of Prepregnancy Body Mass Index and Gestational Weight Gain on
Perinatal Outcomes for Women With Gestational Diabetes Mellitus.
AB - BACKGROUND: Gestational diabetes mellitus (GDM), an obstetric disease that
affects the health of pregnant women, is one of the key factors associated with
perinatal mortality or disease. AIMS: To explore the impact of prepregnancy body
mass index (BMI) and gestational weight gain (GWG) on perinatal outcomes for
women with GDM. METHODS: With a retrospective study design, women were recruited
who received prenatal checkups, gave birth at two teaching hospitals in southern
Taiwan from 1995 to 2011, and received a diagnosis of GDM by an obstetrician. A
trained research assistant collected the participants' data in each hospital's
archives room. The researcher used a retrospective case study method to identify
women who received a GDM diagnosis between 1995 and 2011. RESULTS: Women with GDM
and with an overweight prepregnancy BMI were more likely to have cesarean
deliveries and to use glucose-lowering medicines after delivery. Their newborns
also had a higher birth weight. In addition, gestational hypertension and
cesarean delivery were more common in women with GDM and with excessive GWG than
in women with GDM and with normal GWG. The newborns of women with GDM and with
excessive GWG had higher birth weights and more nuchal cord than those of women
with GDM and with normal GWG. More women with GDM and with excessive GWG
underwent blood glucose monitoring than did women with GDM and with normal GWG.
LINKING EVIDENCE TO ACTION: The prepregnancy weight and GWG significantly
affected perinatal outcomes in both the women with GDM themselves and their
newborns. Healthcare professionals must provide childbearing women with
additional health education in the areas of health promotion, nutrition, weight
control, exercise, and maintaining regular everyday lives.
PMID- 29962103
TI - Evaluation method regarding the effect of psychotropic drugs on driving
performance: A literature review.
AB - Although automobile driving is necessary for many people, including patients with
mental disorders, the influence of psychotropic drugs on driving performance
remains unclear and requires scientific verification. Therefore, the objective of
this study was to conduct a review of the literature in order to aid the
development of a valid evaluation method regarding the influence of medication on
driving performance. We conducted a literature search using two sets of terms on
PubMed. One set was related to psychotropic drugs, and the other to driving
tests. We excluded reviews and case studies and added literature found on other
sites. A total of 121 relevant reports were found. The experiments were roughly
divided into on-the-road tests (ORT) and driving simulators (DS). Although
highway driving tests in ORT are most often used to evaluate driving performance,
DS are becoming increasingly common because of their safety and low cost. The
validity of evaluation methods for alcohol should be verified; however, we found
that there were few validated tests, especially for DS. The scenarios and
measurement indices of each DS were different, which makes it difficult to
compare the results of DS studies directly. No evaluation indices, except for SD
of lateral position, were sufficiently validated. Although highway ORT are the
gold standard, DS were shown to have an increasing role in evaluating driving
performance. The reliability of DS needs to be established, as does their
validation with alcohol in order to accumulate more high-quality evidence.
PMID- 29962106
TI - Central retinal artery occlusion showing features of paracentral acute middle
maculopathy following uncomplicated pterygium surgery.
PMID- 29962107
TI - Improving outcomes in patients with type 2 diabetes mellitus and chronic heart
failure: New hope.
PMID- 29962108
TI - Right of reply to: Robotic-assisted surgical procedures are the future of
gynaecology in Australasia.
PMID- 29962109
TI - Cholesterol Peroxidation as a Special Type of Lipid Oxidation in Photodynamic
Systems.
AB - Like other unsaturated lipids in cell membranes and lipoproteins, cholesterol
(Ch) is susceptible to oxidative modification, including photodynamic oxidation.
There is a sustained interest in the pathogenic properties of Ch oxides such as
those generated by photooxidation. Singlet oxygen (1 O2 )-mediated Ch
photooxidation (Type II mechanism) gives rise to three hydroperoxide (ChOOH)
isomers: 5alpha-OOH, 6alpha-OOH and 6beta-OOH, the 5alpha-OOH yield far exceeding
that of the others. 5alpha-OOH detection is relatively straightforward and serves
as a definitive indicator of 1 O2 involvement in a reaction, photochemical or
otherwise. Like all lipid hydroperoxides (LOOHs), ChOOHs can disrupt membrane or
lipoprotein structure/function on their own, but subsequent light-independent
reactions may either intensify or attenuate such effects. Such reactions include
(1) one-electron reduction to redox-active free radical intermediates, (2) two
electron reduction to redox-silent alcohols and (3) translocation to other lipid
compartments, where (1) or (2) may take place. In addition to these effects,
ChOOHs may act as signaling molecules in reactions that affect cell fates.
Although processes a-c have been well studied for ChOOHs, signaling activity is
still poorly understood compared with that of hydrogen peroxide. This review
focuses on these various aspects Ch photoperoxidation and its biological
consequences.
PMID- 29962110
TI - Incorporating Ionic Paths into 3D Conducting Scaffolds for High Volumetric and
Areal Capacity, High Rate Lithium-Metal Anodes.
AB - Lithium-metal batteries can fulfill the ever-growing demand of the high-energy
density requirement of electronics and electric vehicles. However, lithium-metal
anodes have many challenges, especially their inhomogeneous dendritic formation
and infinite dimensional change during cycling. 3D scaffold design can mitigate
electrode thickness fluctuation and regulate the deposition morphology. However,
in an insulating or ion-conducting matrix, Li as the exclusive electron conductor
can become disconnected, whereas in an electron-conducting matrix, the rate
performance is restrained by the sluggish Li+ diffusion. Herein, the advantages
of both ion- and electron-conducting paths are integrated into a mixed scaffold.
In the mixed ion- and electron-conducting network, the charge diffusion and
distribution are facilitated leading to significantly improved electrochemical
performance. By incorporating Li6.4 La3 Zr2 Al0.2 O12 nanoparticles into 3D
carbon nanofibers scaffold, the Li metal anodes can deliver areal capacity of 16
mAh cm-2 , volumetric capacity of 1600 mAh cm-3 , and remain stable over 1000 h
under current density of 5 mA cm-2 . The volumetric and areal capacities as well
as the rate capability are among the highest values reported. It is anticipated
that the 3D mixed scaffold could be combined with further electrolytes and
cathodes to develop high-performance energy systems.
PMID- 29962112
TI - Who owns your data? Part II ownership of your scholarly article.
PMID- 29962111
TI - Presurgical language fMRI: Technical practices in epilepsy surgical planning.
AB - Little is known about how language functional MRI (fMRI) is executed in clinical
practice in spite of its widespread use. Here we comprehensively documented its
execution in surgical planning in epilepsy. A questionnaire focusing on cognitive
design, image acquisition, analysis and interpretation, and practical
considerations was developed. Individuals responsible for collecting, analyzing,
and interpreting clinical language fMRI data at 63 epilepsy surgical programs
responded. The central finding was of marked heterogeneity in all aspects of
fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4, or
5 tasks with a modal run duration of 5 min. Variants of over 15 protocols are in
routine use with forms of noun-verb generation, verbal fluency, and semantic
decision-making used most often. Nearly all aspects of data acquisition and
analysis vary markedly. Neither of the two best-validated protocols was used by
more than 10% of respondents. Preprocessing steps are broadly consistent across
sites, language-related blood flow is most often identified using general linear
modeling (76% of respondents), and statistical thresholding typically varies by
patient (79%). The software SPM is most often used. fMRI programs inconsistently
include input from experts with all required skills (imaging, cognitive
assessment, MR physics, statistical analysis, and brain-behavior relationships).
These data highlight marked gaps between the evidence supporting fMRI and its
clinical application. Teams performing language fMRI may benefit from evaluating
practice with reference to the best-validated protocols to date and ensuring
individuals trained in all aspects of fMRI are involved to optimize patient care.
PMID- 29962113
TI - Case report: A transplant candidate with unexpected serum reactivity against the
45KE eplet on HLA-B alleles.
AB - This case report describes the serum antibody specificity against the 45KE eplet
which had not been yet shown to be antibody-verified. This antibody was produced
by a 41-year-old European male with Berger's disease. His serum had HLA class I
antibody reactivity as determined in IgG binding assays with single allele panels
(OneLambda, ThermoFisher, Lot 8 and Lot 9). The HLAMatchmaker analysis revealed
reproducible serum reactivity only with alleles carrying the 45KE eplet. The
cause of this 45KE-specific immunization is unknown because this male patient had
never been transfused nor received a previous transplant, Moreover, his mother's
HLA type did not have any 45KE-carrying allele. This finding might be related to
observations reported in the literature about the appearance of HLA-reactive
antibodies following influenza vaccination but this possibility could not be
investigated.
PMID- 29962114
TI - Rise in antifibrotic and decrease in profibrotic microRNA protect the heart
against fibrosis during pregnancy: A preliminary study.
AB - BACKGROUND: Physiological pregnancy is associated with volume overload. Unlike
cardiac pathologies linked with volume overload, such as mitral or aortic
regurgitation, pregnancy is thought to be unrelated to fibrosis of the heart.
However, changes in the cardiac extracellular matrix during pregnancy remain
poorly understood. OBJECTIVES: The aim of the study was to examine the expression
of 11 microRNAs associated with cardiac fibrosis (miR-21, miR-26a, miR-26b-5p,
miR-29b-3p, miR-29c-3p, miR-101a, miR-146a, miR-208a, miR-223 and miR-328) during
pregnancy and to compare them with a healthy control group. MATERIAL AND METHODS:
Six women in singleton pregnancy (30-36 weeks) and 6 non-pregnant women as a
control group were included in the study. Each woman underwent an
echocardiographic examination, and had blood pressure on both arms measured and a
blood sample taken. MicroRNAs expression was analyzed using Custom TaqMan(r)
Array MicroRNA Cards (Applied Biosystems, Foster City, USA). RESULTS: Median age
of the pregnant women was 34 years (range 25-39 years) and of the control group
32 years (range 29-43 years). Median week of pregnancy was 34 years (range 31-36
years). Most of the examined microRNAs had a lower expression in the pregnancy
group (fold change 1.0). CONCLUSIONS: In the 3rd trimester of physiological
pregnancy, there is a 244% increase in expression of miR-101a and a decrease by
73% in expression of miR-328. Both of these changes can protect against fibrosis
during volume overload occurring in physiological pregnancy.
PMID- 29962115
TI - Assessment of markers expressed in human hair follicles according to different
skin regions.
AB - BACKGROUND: Body region-dependent hair follicle (HF) characteristics are
concerned with follicular size and distribution, and have been demonstrated to
have characteristics for each region of the body. OBJECTIVES: The aim of the
present study was to investigate the expression patterns of the markers called
cytokeratin 15 (K15), cytokeratin 6 (K6) and monoclonal antibody Ki-67, and also
apoptosis in HFs, which can be observed in different parts of the human body.
MATERIAL AND METHODS: In this study, healthy human HFs were taken by biopsy from
5 various donor sites of the human body: the scalp, the leg, the abdomen, the
back and waist. HF-containing skin specimens taken using cryosection were stained
with hematoxylin & eosin (H&E) and K15, K6, Ki-67 and terminal deoxynucleotidyl
transferase-mediated digoxigenin-dNTP nick end-labelling (TUNEL)
immunofluorescence staining protocol was performed. RESULTS: Different skin
regions from the human body were examined histologically. While the HFs of scalp
tissue showed anatomically obvious hair layers, some hair sections from other
regions, like the leg, the abdomen, back and waist, were not as distinct as in
the scalp region. According to our findings, K15 expression was highest in the
scalp. In addition, the immunoreactivity (IR) intensity of K15 was significantly
decreased in the HFs on the waist and abdominal regions, compared to the scalp
and back regions (p < 0.001). However, the IR intensity of K6 in the scalp region
was statistically significantly higher than the IR intensity of K6 in the abdomen
region (p < 0.05). Moreover, we showed intraepithelial apoptosis and
proliferation of keratinocytes in the bulge of HF. In the study, Ki-67-positive
and TUNEL-positive cell numbers were not statistically significant (p > 0.05).
CONCLUSIONS: Our findings are important for further investigation of molecular
aspects of the human hair follicle stem cells compartments in health and disease,
which might be a promising model for comparative studies with different human
diseases.
PMID- 29962116
TI - Evidence-based strategies for the minimally invasive treatment of carious
lesions: Review of the literature.
AB - Resulting in a high economic and biological cost, the traditional therapeutic
approach to carious lesion management is still largely restorative. Minimally
invasive (MI) treatment offers an attractive alternative to managing carious
lesions in a more conservative and effective manner, resulting in enhanced
preservation of tooth structure. The aim of this review was to summarize the
evidence behind several MI alternatives for carious lesion management, including
the use of sealants, infiltration, atraumatic restorative treatment (ART), and
selective carious tissue removal (e.g., indirect pulp capping, stepwise removal,
or selective removal to soft dentine). Relevant literature was screened, and
articles reporting randomized controlled trials or systematic reviews of
strategies to manage non-cavitated or cavitated carious lesions in adults and
children were included. Fifty six articles met the inclusion criteria. For non
cavitated lesions, the use of sealants is supported by strong evidence, while the
evidence for infiltration of proximal lesions is moderate. For deep cavitated
lesions, selective removal to soft dentin and/or stepwise excavation is supported
by strong evidence. The use of the ART technique to restore cavitated lesions is
also supported by strong evidence as a suitable strategy that has been used
extensively in the literature concerning non-dental settings. Preservation of
tooth structure through the use of MI treatment for both non-cavitated and
cavitated lesions is supported by moderatestrong evidence, which supports the
paradigm shift towards routine use of more conservative strategies in the
treatment of carious lesions.
PMID- 29962117
TI - Follow-up monitoring of physical activity after rehabilitation by means of a
mobile application: Effectiveness of measurements in different age groups.
AB - BACKGROUND: Active monitoring of the level of daily physical activity seems to be
a useful element for secondary prevention in public health. Low physical activity
increases the incidence of cardiovascular diseases, obesity, diabetes,
musculoskeletal diseases, and causes loss of the previously achieved effects of
rehabilitation. OBJECTIVES: The purpose of this study was to assess the level of
physical activity in different age groups of adults with the use of the
telemedical system based on a mobile application. MATERIAL AND METHODS: The
research covered data collected remotely from 927 individuals of both genders,
aged 20-80 years (group I: 20-40 years, group II: 41-60 years, group III: 61-80
years). A monitoring system (Activity Measurement Tool) developed in the
Department of General Rehabilitation at the Witold Chodzko Institute of Rural
Health (Lublin, Poland) was used to measure home physical activity in the
examined group. The system uses a dedicated mobile application, cellular data
transmission and web data-showing software. Home physical activity was assessed
using the International Physical Activity Questionnaire - Short Form (IPAQ-SF)
and simultaneous processing of data from a smartphone accelerometer. RESULTS: The
mean level of physical activity in the group of active application users (>=2
days, n = 494), expressed as Metabolic Equivalent of Task (MET)-min/week (IPAQ
SF), was as follows: group I (female participants (F): 5,767.9, n = 73; male
participants (M): 4,888.4 n = 251), group II (F: 3,468.7, n = 24; M: 4,053.5, n =
119) and in group III (M: 5,769.3, n = 27; no female participants were involved).
In 72.3% of users, the registered physical activity was smaller in relation to
IPAQ-assessed/7 days physical activity (sign test: n = 494; percentage of
negative differences: 72.3%; Z = 9.9; p = 0.00). CONCLUSIONS: The research
findings indicate a high level of self-reported physical activity among the users
in all age and gender groups, although it is not reflected in the level of
registered activity. Although the level of daily physical activity was evaluated,
it was mainly among young and middle-aged men who gladly and regularly made use
of the measurement possibilities offered by mobile technology.
PMID- 29962119
TI - Steroid Treatment of Optic Neuropathies.
AB - The etiologies of optic neuropathy include inflammation, ischemia, toxic and
metabolic injury, genetic disease, and trauma. There is little controversy over
the practice of using steroids in the treatment of optic neuritis--it is well
established that intravenous steroid treatment can speed visual recovery but does
not alter final visual function. However, there is controversy surrounding the
acceptable routes of administration, dosage, and course of treatment.
Additionally, the typical patient with optic neuritis is young and otherwise
healthy, and thus is likely to tolerate steroids well. In ischemic and traumatic
causes of optic neuropathies, the initial injury is not inflammatory, but damage
may be compounded by secondary injury due to resultant inflammation and swelling
in the confined space of the optic canal. Steroids have been considered as a
means of minimizing inflammation and swelling, and thus minimizing the secondary
injury that results. However, the use of steroids in traumatic and ischemic optic
neuropathies is highly controversial-the evidence for the efficacy of treatment
with steroids is insufficient to show that there is significant benefit.
Additionally, patients with these conditions are more likely to have
comorbidities that make them vulnerable to significant adverse events with the
use of steroids. In this article, we attempt to analyze the current state of the
literature regarding the use of steroids in the treatment of optic neuropathies,
specifically optic neuritis, nonarteritic anterior ischemic optic neuropathy, and
traumatic optic neuropathy.
PMID- 29962118
TI - Pneumonia in Patients with Chronic Obstructive Pulmonary Disease.
AB - Chronic obstructive pulmonary disease (COPD) is a frequent comorbid condition
associated with increased morbidity and mortality. Pneumonia is the most common
infectious disease condition. The purpose of this review is to evaluate the
impact of pneumonia in patients with COPD. We will evaluate the epidemiology and
factors associated with pneumonia. We are discussing the clinical characteristics
of COPD that may favor the development of infections conditions such as
pneumonia. Over the last 10 years, there is an increased evidence that COPD
patients treated with inhaled corticosteroids are at increased risk to develp
pneumonia. We will review the avaialbe information as well as the possible
mechanism for this events. We also discuss the impact of influenza and
pneumococcal vaccination in the prevention of pneumonia in COPD patients.
PMID- 29962120
TI - [Spatial-Temporal Change Evolution of PM2.5 in Typical Regions of China in Recent
20 Years].
AB - Two decades of PM2.5 pollution has seriously hindered China's sustainable
development. However, relevant research of PM2.5 has been hindered because of the
lack of long-term historical monitoring data. Therefore, ground observations of
PM2.5 concentration from 2013 to 2016 in four typical regions of China and the
MODIS aerosol optical thickness data, boundary layer height, temperature, and
other meteorological data from 2000 to 2016 were used as the basic data. A
combined simulation model was constructed by combining the two algorithms of
backward artificial neural network and support vector regression and obtains the
PM2.5 concentration history for the past 20 years using geospatial analysis
technology. The results demonstrate that the combination model is better than the
single model, with lower error and higher generalization ability. The spatial
temporal analysis results show that the concentration of PM2.5 continued to
increase in the Beijing-Tianjin-Hebei region and in the three northeastern
provinces of China, the PM2.5 concentration decreased slowly in the Pearl River
Delta, the pollution range of PM2.5 in three of the research areas showed an
expanding trend, and the PM2.5 concentration and pollution range remained stable
in the Yangtze River Delta. In 2012, the concentration of PM2.5 in the four study
areas decreased and the pollution range narrowed, but the PM2.5 concentration
rose slightly after that decline and the high pollution range narrowed during
2013-2016, which with the country to take PM2.5 regional defense and other
governance measures.
PMID- 29962121
TI - [Evaluation the Extent of Health Damage Caused by PM2.5 Particulate in Xi'an
City].
AB - The study evaluated the acute health damage effect of PM2.5 exposure in winter in
Xi'an City, using the average concentration of PM2.5 (24 h) and the Average
Poisson Regression Model for three consecutive years, from 2014 to 2016. The
Corrected Human Capital Method was used to evaluate the economic loss from
premature death. The cost of illness was used to assess the economic loss of
hospitalization, illness and clinic. The results show that the economic loss in
the study period (2014, 2015, 2016) caused by PM2.5 was about 33.523 billion yuan
(95% CI: 24.961-36.975), 21.105 billion yuan (95% CI: 13.560-26.880), and 37.132
billion yuan (95% CI: 27.246-41.164). The proportions of GDP were as follows:
6.10% (4.54%-6.73%), 3.64% (2.34%-4.63%), and 5.91% (4.34%-6.55%) for each of the
three years. The health economic loss was positively correlated with the average
PM2.5 concentration in winter. PM2.5 pollutants have a significant impact on the
health of residents in Xi'an. The number of reported cases was about 1071338 (95%
CI: 646432-1385847), 438273 (95% CI: 246842-599989), and 1019503 (95% CI: 611407
1324547) for each of the three years. The effects on children with asthma were
significantly higher than that on adults, while adults with chronic bronchitis
were affected more significantly than children. This study can provide a
scientific basis for cost-benefit analysis of the PM2.5 air quality standard in
Xi'an, and provide a reference for the management of environment quality.
PMID- 29962122
TI - [Analysis of Chemical Composition, Source and Evolution of Submicron Particles in
Xianghe, Hebei Province].
AB - Haze formation is closely related to the chemical composition of fine particles.
An aerosol chemical speciation monitor (ACSM), aethalometer, etc. were used to
investigate the chemical components, source, and evolution of submicron particles
at Xianghe, a suburban site located between the megacities of Beijing and Tianjin
from May 31 to June 30, 2013. The results suggest that the air quality in Xianghe
has suffered severe deterioration, which is imminent to improve air quality and
pollution. On average, PM1 accounted for ~71% of PM2.5 and PM1 distributed in 20
80 MUg.m-3 mainly. Organic aerosols had a high degree of oxidation. Significant
straw burning events were observed during June 2013 in Xianghe. During the straw
burning period, the mass concentration of PM1 significantly increased and the
mass fraction of organic aerosols in PM1 rapidly increased to about 47%, on
average. The contribution of nitrate was generally greater than that of other
inorganic components. Affected by the straw burning events, the aerosol acidity
turns from weak alkaline to weak acid. Positive matrix factorization was
performed on the ACSM OA mass spectra, which identified two primary OA (POA),
i.e., BBOA and HOA, and two secondary OA (SOA), i.e., LV-OOA and SV-OOA, factors.
The SOAs dominated the OAs during the observation, contributing ~69% of OAs.
However, after the straw burning period was removed, the positive matrix
factorization (PMF)results did not reveal biomass combustion organic aerosols.
PMID- 29962123
TI - [Characteristics and Source Analysis of Carbonaceous Components of PM2.5 During
Autumn in the Northern Suburb of Nanjing].
AB - In this study, PM2.5 samples were collected from October to November of 2015 in
the northern suburb of Nanjing. The mass concentrations of organic carbon (OC),
elemental carbon (EC), and levoglucosan in the samples were analyzed by thermal
optical transmittance (TOT) and ion chromatography. The average concentrations of
OC and EC were respectively (11.3+/-4.9) MUg.m-3 and (1.1+/-0.9) MUg.m-3. The
average total carbon (TC) was 22.9%, and the OC/EC was 7.4. The quality
concentrations of PM2.5, OC, EC, and SOC all reflected daytime features, and the
correlation between OC and EC was better during the day than at night
(correlation coefficients of 0.86 for day and 0.7 for night). By analyzing the
mass concentrations of PM2.5, levoglucosan, and SOC, as well as the data of
backward trajectories and fire point data, it was determined that the northern
suburb of Nanjing is affected by the long-distance transportation of biomass from
Hebei and other places from October 13-16. The correlations between levoglucosan
and OC, EC, or SOC were significant (correlation coefficients of 0.78, 0.79, and
0.65, respectively), and the contribution of biomass combustion during sampling
to OC was 21.9%.
PMID- 29962124
TI - [Comparison of Chemical Components Characteristics of PM2.5 Between Haze and
Clean Periods During Summertime in Lin'an].
AB - PM2.5 samples were collected at a background site of the Yangtze River Delta in
China, during summertime, of which the carbonaceous components, i.e., OC and EC,
and water-soluble inorganic ions, including sulfate, nitrate, and ammonium, were
quantified. The average concentrations of OC and EC in PM2.5 during summer at
Lin'an were (14.3+/-3.95) MUg.m-3 and (3.33+/-1.47) MUg.m-3, respectively.
Compared to an urban site, the correlation between OC and EC during summertime in
Lin'an, which was a rural site, was relatively weak (R2=0.31, P<0.01). The
concentrations of secondary inorganic aerosols (sulfate as SO42-, nitrate as NO3
, and ammonium as NH4+) were much higher than those of other water-soluble
inorganic ions, with average values of (8.70+/-5.66), (2.04+/-1.07), and (3.25+/
2.29) MUg.m-3, respectively. Based on long-term intensive observations, combined
with the analysis of back trajectory and fire spots observations, it was revealed
that regional transport and stable synoptic conditions both play important roles
in controlling the variations in aerosol chemical components. During the
transition from clean to hazy days, the EC and POC fractions showed no obvious
variation; in contrast, the SOC fraction decreased obviously. Unlike for SOAs,
relative contributions of sulfate and ammonia to PM2.5 increased during hazy
days, suggesting enhanced chemical production via other pathways for these two
secondary inorganic ions, probably through heterogeneous reactions.
PMID- 29962125
TI - [Characteristics and Sources of Carbon Components in PM2.5 During Autumn and
Winter in Panjin City].
AB - In order to study the pollution characteristics and sources of carbon in Panjin
City during autumn and winter, PM2.5 samples were collected at three monitoring
points in October 2016 and January 2017. Pollution characteristics and sources of
carbon components in PM2.5 were analyzed by the OC/EC ratio method, EC tracer
method, and principal component analysis method. The results showed that the
PM2.5 concentration exceeded the ambient air quality standard (GB 3095-2012) and
that the average concentrations of OC and EC were 10.02 MUg.m-3 and 3.91 MUg.m-3
in autumn, respectively, and 16.04 MUg.m-3 and 5.62 MUg.m-3 in winter. According
to the OC/EC ratio method, the OC/EC ratios were more than 2.0 during the
sampling periods, indicating that there was secondary pollution in autumn and
winter. Spearman correlation analysis and linear fitting indicated that the OC
and EC sources were complex in development zones and that secondary school and
cultural park areas may have similar sources during autumn and winter. SOC was
quantitatively estimated by the EC tracer method, with concentrations of 7.21
MUg.m-3 and 23.07 MUg.m-3 in autumn and winter, respectively. The absolute and
relative errors of SOC uncertainty were 0.98 MUg.m-3 and 14.00% in autumn,
respectively, and 1.87 MUg.m-3 and 8.21% in winter. Based on the method of
principal component analysis, the carbon components in autumn and winter were
mainly derived from coal combustion, biomass burning, and vehicle exhaust.
PMID- 29962126
TI - [Aerosol Optical Properties and Light Absorption Enhancement of EC During
Wintertime in Nanjing].
AB - A three-wavelength photoacoustic soot spectrometer (PASS-3) was employed for real
time online measurement of aerosol optical properties and light absorption
enhancement of EC together with chemical composition analysis in the northern
suburb of Nanjing during January 1-19, 2016. The average aerosol absorption
coefficient, scattering coefficient, and single scattering albedo at 532 nm
during the observation period were (64.19+/-35.28) Mm-1, (454.68+/-238.71) Mm-1,
and 0.87+/-0.03, respectively, and showed clear diurnal variation, mainly
affected by planetary boundary layer height and PM2.5 mass concentration. The
mass absorption cross section (MAC) showed an increasing trend during the
observation period, consistent with the trend of variation in ratios between non
EC and EC components, resulting from the difference in relative percentage of
secondary materials and coating thickness under different pollution conditions.
The estimated light absorption enhancement, denoted EMAC, was calculated based on
the change in MAC. The campaign-averaged EMAC at 405, 532, and 781 nm were 1.53+/
0.56, 1.34+/-0.47, and 1.14+/-0.40, respectively, showing a decrease with
increasing wavelength, suggesting the contribution of brown carbon (BrC). All non
EC components showed linear correlation with EMAC, with the most significant
correlation between OC/EC and EMAC, indicating that an increase in organics was
likely the main contributor to light absorption enhancement in our study. In
addition, the high correlation of K+/EC and EMAC revealed the contribution of
biomass burning.
PMID- 29962127
TI - [Concentration, Solubility, and Dry Deposition Flux of Trace Elements in Fine and
Coarse Particles in Qingdao During Summer].
AB - PM2.5 and total suspended particulate (TSP) samples were synchronously collected
in Qingdao from June to July 2016. The total and water-soluble concentrations of
12 trace elements in these samples were analyzed to investigate their
distribution characteristics in fine and coarse particles as well as their dry
deposition fluxes. The results showed that the total mass concentrations of Al,
Fe, Sr, Mn, and Ba, which are expected to mainly originate from crustal sources,
were generally distributed in the coarse particles, and the part mass in the
coarse mode accounted for 55%-60% of their total concentrations. Cr, Ni, V, Zn,
Pb, As, and Cd, which mainly originate from anthropogenic contributors, generally
existed in fine particles where the part mass accounted for 65%-85% of their
total concentrations. The soluble mass concentrations of trace elements, whether
from crustal or anthropogenic sources, were mainly distributed in the fine
particles. The proportions of Al, Fe, Mn, and Ba in soluble mass concentration
existing in the fine particles were 50%-80% and 70%-90% for Cr, Ni, V, Zn, Pb,
As, and Cd. The solubility of trace elements was higher in fine particles than in
coarse particles. The soluble concentrations of trace elements exhibited a
positive correlation with acid compounds, and the solubility exhibited a negative
correlation with pH in the fine particles, implying that acidification processes
play a key role in determining the solubility of trace elements in fine
particles. The soluble fractions in the total dry deposition flux of Al and Fe
were only 1%-2%; that of Sr, Ba, Cr, and Pb were about 30%-40%; and that of Mn,
Ni, V, Zn, As, and Cd were about 50%-60%. The atmospheric deposition of soluble
Fe supported phytoplankton carbon production of (194+/-150) mg.(m2.d)-1,
contributing about 10% of the primary productivity in the Yellow Sea.
PMID- 29962128
TI - [Characteristics and Sources of Dissolved Heavy Metals in Summer Precipitation of
Taiyuan City, China].
AB - To investigate the characteristics and sources of dissolved heavy metals in
precipitation of Taiyuan, 61 precipitation samples were collected using an
automated dry and wet sampler from 2013 to 2015 during summertime. The
concentrations of 12 dissolved heavy metals were detected using ICP-MS, and wet
deposition fluxes and sources were analyzed. The results showed that the pH
ranged from 4.34 to 7.95, with a volume-weighted mean of 5.37. The mean
concentration of the dissolved heavy metals was 236.931 MUg.L-1, with a range of
66.324 to 1029.212 MUg.L-1. Zn and Fe were the major components, together
accounting for 53.39% of the total concentrations. The wet deposition fluxes of
the 12 dissolved heavy metals reached 1.735 mg.(m2.d)-1. The enrichment factors
of Ba, Cu, Sr, Zn, As, Cd, and Pb were all in excess of 100, suggesting that
these metals were seriously influenced by anthropogenic activities. Results from
positive matrix factorization (PMF) indicated that steel smelting emissions, coal
combustion, vehicle emissions, and crustal dusts were the major sources of heavy
metals in the precipitation of Taiyuan City, with average contributions of
38.34%, 23.06%, 20.45%, and 18.15%, respectively. According to backward
trajectory analysis, air masses from the southwest and southeast directions
contributed the most to precipitation during summer in Taiyuan, with percentages
of 38 and 35, respectively. The southern industrial areas located in the Yuncheng
Linfen-Jinzhong and Jincheng-Changzhi-Jinzhong regions should be paid more
attention.
PMID- 29962129
TI - [Characteristics of and Factors Affecting Atmospheric CO2 Concentration in
Hangzhou].
AB - In situ measurement of CO2 concentration(volume fraction) was carried out in both
urban and rural areas of Hangzhou from August 2015 to September 2016. The
characteristics of CO2 concentration at the urban site were compared to those at
the rural site, and the factors affecting CO2 concentration in Hangzhou were
analyzed via wind direction, weekday-weekend difference in CO2 concentration, and
evolution of CO2 concentration during the G20 summit. The results revealed that
the diurnal variation of CO2 concentration in both the urban and rural areas
presented a single peak curve most of the time, which resulted from the daily
evolution of plant photosynthesis/respiration and atmospheric transport
conditions. The diurnal variation of the difference in CO2 concentration observed
at the urban and rural sites showed a bimodal peak curve, because anthropogenic
emissions played a more important role. The diurnal amplitude of CO2
concentration in rural area was higher than that in urban area in spring and
summer, but lower in autumn. The seasonal variation of CO2 concentration in both
the urban and rural areas showed the same trend, with higher values appearing in
winter and spring and lower values in summer. The difference in CO2 concentration
observed at the urban and rural sites reached its highest level in winter, and
dropped to its lowest in summer. The wind direction induction of high CO2
concentration was consistent with the location of the surrounding urban areas. A
weekday-weekend difference in CO2 concentration was observed in Hangzhou,
especially in urban area, as traffic emissions had an impact on the weekday
weekend difference in diurnal distribution of CO2 concentration. The average
volume fraction of CO2 in urban area of Hangzhou was 9.3*10-6 higher than that in
rural area, and the reduction of anthropogenic emissions during the G20 summit
reduced the atmospheric CO2 concentration effectively, especially in urban area.
PMID- 29962130
TI - [Treatment Status and Emission Characteristics of Volatile Organic Compounds from
Typical Industrial Sources].
AB - The status of treatment equipment, the emission characteristics, and the ozone
formation potential (OFP) of volatile organic compounds (VOCs) for 11 typical
enterprises, which were categorized into the 8 major VOC emission industries
identified by the emission inventory of a typical city in the Yangtze River
Delta, are discussed in this paper. There was a large difference in the removal
efficiency of non-methane hydrocarbon (NMHC) between different treatment
techniques, and even an increase in concentration occurred after some of the
treatments. The current treatment equipment for VOCs needs further optimization.
The emissions of NMHC, benzene, toluene, and xylene in most of the surveyed
enterprises exceeded their corresponding standards, with toluene the worst
offender. The most abundant compounds in the eight emission industries were
aromatic hydrocarbons and oxygenated VOCs, whereas aromatic hydrocarbons
contributed the most to ozone formation potential. There were large differences
in emission characteristics of VOCs from different industries. Priority should be
placed on the industries that have large OFP when control strategies of VOCs are
considered.
PMID- 29962131
TI - [Characteristics of Industrial VOCs Emission Sources and Control Technology
Application in a Prefecture-level City Region-Based on Qinhuangdao City].
AB - Volatile organic compound (VOCs) emissions and control technologies of about 609
industrial enterprises in Qinhuangdao City were investigated in this study. The
results showed that the exhausted emission flow rates from the industries of oil
processing, coking, and nuclear fuel processing were found to be the largest
sources of VOCs in Qinhuangdao City (normally above 105 m.h-1), whereas the other
industrial emission flow rates were mainly within the range of 103-105 m3.h-1.
The detected VOC concentrations for all the industries were less than 1000 mg.m
3. The VOCs emission rates were between 50-10000 g.h-1, but demonstrated
different characteristics among the various industries. It was found that the
industries of transportation equipment manufacturing, petroleum processing,
coking, nuclear fuel processing, machinery and equipment manufacturing, printing
and reproduction of recorded media, and chemical raw material and chemical
product manufacturing had much higher concentrations and emission rates than
other industries did. However, the overall VOCs emission level from this city was
still lower when compared to previous reports for other regions of China. The
investigation of the VOCs control technology application showed that there were
109 constructed or operated VOCs treatment facilities among the 609 industrial
enterprises. Activated carbon adsorption technology accounted for the largest
proportion among the various techniques, with 69%, followed by absorption
technology (19%).
PMID- 29962132
TI - [Pollution Condition and Health Risk Assessment of VOCs in Fermentation Exhaust
from Penicillin Production].
AB - Penicillin is the most widely used and longest-lived antibiotic in the
pharmaceutical industry. It belongs to the bio-fermentation chass of drugs, with
a large amount of fermentation exhaust containing volatile organic compounds
(VOCs) generated during the process of penicillin production, which have a
serious impact on the environment. In this study, the pollution characteristics
of the fermented exhaust are studied by using investigation and testing the
souces of the pollution and via a health risk assessment model. The main results
show that 23 kinds of VOCs were detected in the penicillin fermentation exhaust.
The main pollutants included vinyl acetate trifluorotrichloroethane,
dichlorotetrafluoroethane, and methylene chloride. In the heating stage, holding
stage, cooling stage, and fermentation stage, the proportion of chlorinated
hydrocarbons was the highest, followed by esters, and the total amount of these
two kinds of substances accounted for more than 90% of total volatile organic
compounds (TVOCs). Using the model of health risk assessment, the noncarcinogenic
risk value of the total fermented exhaust was 4.98*10-5, which estimating the
risk value by concentration gradient expansion is much lower than the maximum
acceptable level (5*10-5 a-1) recommended by the International Commission on
Radiation Protection (ICRP), which will not cause certain non-carcinogenic risk
to the exposed population. VOCs in fermentation exhaust also have carcinogenic
effects on human beings. The main health hazards to humans are 1,3-butadiene,
dichloromethane, methyl chloride, carbon tetrachloride, benzene, and 1,1
dichloroethane.
PMID- 29962133
TI - [Measurements of OC and EC Emission Factors for Light-duty Gasoline Vehicles].
AB - Organic carbon (OC) and elemental carbon (EC) emission factors from 27 State 3-5
light-duty gasoline vehicles (LDGVs) were tested in this study using a CVS
(Constant Volume Sampling) system on a dynamometer. The influences of start
conditions, driving cycles, and fuel injection technologies on the OC and EC
emissions were analyzed. The results show that the OC emission factors of the
tested State 3 to 5 LDGVs were (2.09+/-1.03), (1.59+/-0.78), and (0.75+/-0.31)
mg.km-1, respectively, and the EC emission factors were (1.98+/-1.42), (1.57+/
1.80), and (0.65+/-0.49) mg.km-1. Both OC and EC emissions significantly
decreased with the promotion of emission standards. The OC/EC ratios were 1.54+/
0.92, 1.53+/-0.91, and 1.47+/-0.66, respectively. OC1, OC2, EC1, and EC2 were the
most important carbonaceous components from LDGVs, accounting for 15%, 20.6%,
22.2%, and 21.7%, respectively. OC and EC emission factors under cold-start
conditions were 1.4 and 1.8 times those under hot-start conditions. OC and EC
emission factors for highway cycles were 2 and 4 times those for urban cycles. OC
emission factors from GDI (Gasoline Direct Injection) engines were close to those
from PFI (Port Fuel Injection) engines. However, their EC emission factors were
1.7 times those from PFI engines. With the increasing popularity of GDI engines
in LDGV fleets in China, the EC emissions from these engines should be paid more
attention in the future.
PMID- 29962134
TI - [Pollution Levels and Risk Assessment of Heavy Metals from Atmospheric Deposition
in Nanjing].
AB - In order to evaluate the pollution levels of and risk from heavy metals in the
atmospheric deposition of different functional urban districts, dust samples were
collected from 20 sampling sites in typical industrial, traffic, residential, and
educational districts of Nanjing. The concentrations of As, Ba, Cd, Co, Cr, Cu,
Fe, Mn, Ni, Pb, Sr, Ti, V, and Zn were analyzed. The potential ecological risk
and health risk were evaluated using the potential ecological risk index and U.S.
EPA's health risk assessment models. Enrichment factors, correlation analysis,
and principal component analysis were used to analyze the sources of heavy
metals. Results showed that the concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Pb,
and Zn were the highest in the industrial district and the concentrations of Ba,
Ni, Ti, and V were the highest in the traffic district. The value of the
potential ecological risk index was the highest in the industrial district and
lowest in the educational district. Meanwhile, the ecological risk of Cr was the
highest, achieving a moderate ecological hazard level. None of the studied heavy
metals had noncarcinogenic risk or carcinogenic risk, according to the results of
health risk assessment. Source analysis indicated that heavy metals in the
atmospheric deposition from the study areas were mainly from traffic and
industrial activities, coal combustion, natural process and life sources.
PMID- 29962135
TI - [Contamination Levels and Source Analysis of Heavy Metals in the Finer Particles
of Urban Road Dust from Xi'an, China].
AB - Road dust samples were collected from four different functional areas in Xi'an
City, i.e., an educational area, a residential area, a park area, and a traffic
area, to study the influence of intensive human activities on local urban
environmental quality. The contents of Cu, Pb, Zn, Cr, Co, V, Mn, and Ni in the
smaller than 63 MUm road dust particles were determined by X-ray fluorescence
spectrometry, and the pollution levels of these metals were assessed by a
geoaccumulation index and a pollution loading index. The possible sources of
heavy metals measured in the dusts were identified by multivariate statistical
analysis methods, including correlation analysis, principal component analysis,
and cluster analysis, and the contributions of each source to heavy metals in the
dusts were apportioned by a principal component analysis-multiple linear
regression receptor model. The results showed that the contents of Cu, Pb, Zn,
Cr, Co, V, Mn, and Ni in the smaller than 63 MUm road dust particles of urban
road dust from Xi'an ranged 14.2-96.9, 23.5-206.1, 20.0-899.4, 122.7-262.8, 7.9
14.2, 48.7-71.5, 274.0-448.9, and 22.4-62.5 mg.kg-1, respectively, with averages
of 46.6, 97.4, 169.2, 177.5, 9.8, 57.1, 337.6, and 29.3 mg.kg-1. Compared to the
element background values of Shaanxi soil, the finer particles of road dust from
Xi'an had elevated contents of Cu, Pb, Zn, and Cr. The finer particles of road
dust from Xi'an were unpolluted by Co, V, Mn, and Ni; unpolluted to moderately
polluted by Cr, Cu, and Zn; and moderately polluted by Pb. The assessment results
of comprehensive pollution indicated that the pollution levels of the heavy
metals in the dusts were mainly unpolluted to moderately polluted. The
multivariate statistical analysis results displayed that Cr, Cu, Pb, and Zn had
significant positive correlation. These metals belong to a principal component
and a cluster, whereas Mn, Ni, V, and Co belong to another principal component
and cluster and have significant positive correlation. Considering the content
characteristics of heavy metals in the dusts, these results illustrated that two
kinds of sources for the heavy metals studied existed for the finer particles of
road dust from Xi'an, i.e., Cu, Pb, Zn, and Cr mainly originated from traffic
sources, whereas V, Co, Mn, and Ni were mainly from natural sources. The
contributions of traffic sources and natural sources to the heavy metals in the
finer particles of the road dust from Xi'an were respectively 56.7% and 43.3%.
PMID- 29962137
TI - [Major Ionic Features and Their Possible Controls in the Surface Water and
Groundwater of the Jinghe River].
AB - To study the hydrochemical characteristics of tributaries of the Jinghe River
(Heihe River Basin) and their controlling factors, from 2014 to 2015, 242 samples
of surface water and groundwater were collected during the dry and flood seasons
from the Jinghe River. After determining the main water chemical ion content by
comprehensively using correlation analysis, Piper three-line graphs, and Gibbs
graph, the spatiotemporal changes in the hydrochemical characteristics of the
Heihe River Basin were analyzed. The results showed that all the water samples in
the study area were weakly alkaline. In the dry season of 2014, the cations in
the surface water and groundwater were mostly Na+, accounting for 56% and 58% of
the total cations, respectively. The anions were mainly SO42-, accounting for 33%
and 39% of the total anions, respectively. In the other three periods, the main
cation and anion components were HCO3- and Na+, accounting for 44%-46% and 42%
56% of the corresponding totals, respectively. In the dry season, the TDS of
surface water and groundwater gradually increases along the river from upstream
to downstream. From the dry season to the flood season, the hydrochemical types
of the surface water changed from Na-Mg-Cl-SO4 to Ca-Mg-HCO3 and of the
groundwater from Mg-Cl-SO4 to Ca-Na-HCO3. Most of the water chemistry samples
were distributed in the middle and upper parts of the Gibbs diagram, indicating
that the formation of hydrated chemical ions in the basin was mainly affected by
rock weathering and evaporation-enrichment. However, the effects of human
activities on water chemistry were more significant in the dry season than in the
flood season.
PMID- 29962136
TI - [pCO2 in the Main Rivers of the Three Gorges Reservoir and Its Influencing
Factors].
AB - An extensive investigation on the main tributaries of the Three Gorges Reservoir
(TGR) region was conducted in autumn (Oct. 2015), with focuses on riverine CO2
partial pressure (pCO2) and its associated controls. Our results indicated that
pCO2 in the main rivers of the TGR region ranged from 18.75 to 296.31 Pa, with a
mean value of (141.06+/-77.51) Pa in the autumn, which was much higher than the
atmospheric CO2 concentration. Therefore, the studied rivers acted as an
atmospheric CO2 source, and the mean CO2 emission rate to the atmosphere was
estimated at (101.1+/-78.0) mmol.(m2.d)-1. The highest and lowest values were
(131.9+/-101.8) and (70.3+/-54.3) mmol.(m2.d)-1, respectively. pCO2 in the main
rivers of the TGR area was significantly related to DO, pH, and bicarbonate.
Furthermore, the biogeochemical process of within-river respiration of organic
carbon rather than photosynthesis resulted in negative relationships between pCO2
and DO or pH because of the high velocities and short residence time in these
mountainous rivers and streams. Our results will help to accurately develop the
carbon budget for the rivers of the Three Gorges Region.
PMID- 29962138
TI - [Urban Runoff Phosphorus Removal Pathways in Bioretention Systems].
AB - The role of vegetation and saturated zones in stormwater-dissolved phosphorus
(PO43--P) removal was investigated using bioretention microcosms. Nine
bioretention columns were dosed with synthetic stormwater under various
hydrological conditions and phosphorus loading rates and monitored over a 12
month period. Remarkable phosphorus removal (>90%) was achieved using the mixed
filter media of sand and local soil, with or without vegetation. Bioretention
columns in which P. alopecuroides was planted could significantly enhance PO43--P
removal. The saturated zones could also reduce the effluent PO43--P
concentrations, but had no significant effect on total phosphorus removal.
Approximately 50% of the input phosphorus retained in the filter media was
extracted in the top 0-22.5 cm, where it could be available for uptake by plants.
Further, 57.1% to 76.1% of the total phosphorus input recovered in the total
plant biomass was stored in the above-ground shoots. Thus, periodic harvesting of
shoots can be a sustainable method of phosphorus removal from stormwater
bioretention systems.
PMID- 29962139
TI - [Succession Characteristics of Phytoplankton Functional Groups and Their
Relationships with Environmental Factors in Dianshan Lake, Shanghai].
AB - Dianshan Lake, a subtropical shallow lake, is one of the main drinking water
sources of Shanghai City. In order to explore the characteristics of
phytoplankton functional groups (PFGs) and their relationships with environmental
factors in Dianshan Lake, phytoplankton and water samples collected from January
2015 to December 2016 were characterized. Results suggested that there were 26
PFGs during our study period. The biomasses of 15 PFGs (B, C, D, F, G, H1, J, Lo,
M, MP, P, W1, W2, X1, and X2) were dominant and had marked annual succession
patterns: D/C Lo/C/MP MP/J/P/W1 P in 2015 and P W2/Lo W2/G/M/H1 P in 2016. To
elucidate the relationships of PFGs with the environmental factors, canonical
correspondence analysis (CCA) was conducted. Results showed that water level
fluctuation (WLF), dissolved oxygen (DO), water temperature (WT), total
phosphorus (TP), electrical conductivity (EC), transparency (SD), and total
nitrogen (TN) were the main impact factors associated with the composition
variations of PFGs in Dianshan Lake. From this study, it is proposed that the
effects of nitrogen, phosphorus, and WLF on the PFGs in Dianshan Lake should be
paid more attention.
PMID- 29962140
TI - [Spatio-temporal Variations of Diatom Community and Their Relationship with Water
Environment in Fuxian Lake].
AB - Fuxian Lake is an important deep lake in China with trophic status generally
categorized as class I. However, there exists a trend of degradation in its
ecological and environmental health under the increasing impacts derived from
catchment development and recent global warming. Therefore, it is important to
evaluate the community composition, distribution patterns, and driving factors of
lake biota. In order to uncover the spatio-temporal variations in water quality
and diatom communities, a monthly survey of diatom community composition and
limnological characteristics was carried out in the surface waters of three
sampling sites from the south, middle, and north of the lake basin in Fuxian in
2015. A total of 166 diatom species belonging to 31 genera were identified, which
was dominated by planktonic diatoms with the extirpation of Cyclotella rhomboideo
elliptica, an endemic species for Yunnan. Diatom community structure showed
significant seasonal succession across the three sites, which were dominated by
Fragilaria crotonensis in January and February, by Aulacoseira granulata in
March, by Cyclotella ocellata and F. crotonensis in April, and by C. ocellata for
other months (i.e., relative abundance of ~80%). Over the spatial scale, the
distribution of the dominant diatoms displayed a high degree of similarity.
Principal component analysis further showed that there existed significant
difference in the diatom community structure and lake environment over the
temporal scale, but no significant deviance was found across the three sites. The
results of redundancy analysis and variation partitioning revealed that the key
driver included meteorological and physical factors (i.e., water temperature,
wind velocity, and Secchi depth), which accounted for 27.6% of the total variance
in diatom community changes. In combination with the thermocline analysis, the
change in lake hydrodynamics may have influenced the thickness and duration of
the thermal stratification of lake water, resulting in the reorganization of the
diatom community. At the same time, the lake-water nutrients and ions also
exerted an important influence on community structuring, which explained the
21.2% and 9.4% of the diatom variation, respectively. Therefore, regional warming
and catchment development have significantly structured the biological community
and ecosystem health of Fuxian Lake. In all, measures should be taken not only to
control the watershed input of pollutants but also to actively mitigate the long
term impact of climate change for the protection and ecological remediation of
Fuxian Lake.
PMID- 29962141
TI - [Effects of Algal Blooms and Their Degradation on the Sediment-water Micro
interface].
AB - Effects of algal blooms and their degradation on the sediment-water micro
interface under conditions of disturbance and darkness were investigated. The
concentration of chlorophyll a in water was determined via the acetone method,
profiles of oxygen near the interface were measured using a microelectrode, and
profiles of nutrients and metals in sediments were measured at the millimeter
level. The results showed that algal bloom degradation at the sediment-water
micro-interface decreased the concentration of oxygen and affected nutrient and
metal profiles, at depths over approximately 3 mm. Disturbance played an
important role in algal bloom degradation and early diagenesis processes of
nutrients, such as C and P, and metals, such as Fe, Ca, Mg, Al, and K. Darkness
sped up algal bloom degradation and reduced the influence of disturbance. Under
control conditions of no disturbance nor algae, and supplied with enough light, a
layer of benthic algae appeared at the sediment surface, whose photosynthesis
produced oxygen and greatly changed the microenvironment. This brought about
significant differences in the concentrations of nearly all nutrients and metals
in the surficial sediment compared with those of other treatments. Correlation
analyses showed that the vertical variability of sediment P concentration was
most strongly related to sediment Mn, followed by sediment C. The results of this
high-resolution research showed that algal bloom degradation had an effect on the
sediment-water micro-interface at the millimeter level.
PMID- 29962142
TI - [Effect of Biochar on Root Morphological Characteristics of Wetland Plants and
Purification Capacity of Constructed Wetland].
AB - A constructed wetland with Acorus calamus L. was built. Straw biochar, reed
biochar, and sawdust biochar was added into the constructed wetland individually
to study the effect of different biochars on the root morphology, dissolved
oxygen, and purification ability of the constructed wetland. The results show
that the total root length, total projection area, total volume, total surface
area, root number, branch number, and root dry weight of Acorus calamus L.
significantly increased when all three kinds of biochar were added into the
constructed wetland (P<0.05). Similarly, adding the biochars into the constructed
wetland also significantly increased dissolved oxygen content in the wetland
(P<0.05). Addition of sawdust biochar into the constructed wetland increased the
root length, projection area, surface area, total volume, number of root tips,
number of branches, and root dry weight of Acorus calamus L. by 96.1%, 106.2%,
185.6%, 172.5%, 75.3%, 121.6%, and 84.9%, respectively. After adding biochars
into the constructed wetland, the root morphology of Acorus calamus L. and
dissolved oxygen content was significantly correlated with removal rate of TN,
TP, and COD, respectively. Addition of sawdust biochar into the constructed
wetland significantly increased the removal rates of total nitrogen, total
phosphorus, and COD when the hydraulic load was 0.022 m3.(m2.d)-1 (P<0.05). These
results suggested that the addition of sawdust biochar to the constructed wetland
increased the root growth of Acorus calamus L. and enhanced dissolved oxygen
content, resulting in purification capacity of the constructed wetland.
PMID- 29962143
TI - [Preparation of Mn-Co/Ceramic Honeycomb Catalyst and Its Performance on Catalytic
Ozonation of Hydroquinone].
AB - In order to improve the activity and working life of metal catalysts in the
heterogeneous catalytic ozonation of organic wastewater, four kinds of Mn
Co/ceramic honeycomb (CH) catalysts with different mass ratios of Mn and Co were
prepared by coating method using cobalt nitrate hexahydrate [Co(NO3)2.6H2O] and
manganese nitrate [Mn(NO3)2] as precursors, respectively, and CH as the carrier.
The structure of the catalysts was analyzed via X-ray diffraction (XRD), N2
adsorption/desorption, field emission scanning electron microscopy (FESEM), and X
ray photoelectron spectroscopy (XPS). The mechanical properties of the catalysts
were studied. The reaction kinetics model of O3 alone and catalytic ozonation of
the hydroquinone were established and catalytic ozonation performance of
catalysts was investigated. The results showed that the crystal phase of
Mn0Co1/CH belonged to CoAl2O4 and that the crystal phase of the Mn-Co/CH catalyst
(Mn1Co1, Mn2Co1, and Mn3Co1) mainly belonged to Mn3O4 and CoO. In particular, the
Mn1Co1/CH catalyst had a large specific surface area of 190 m2.g-1, high pore
volume of 0.25 cm3.g-1, and pore size of 4.8 nm. The highest catalytic activity
was obtained when Mn?Co was 1?1 (Mn1Co1/CH catalyst). The catalytic activity of
the Mn1Co1/CH catalyst was the highest, and removal efficiencies of hydroquinone
and COD were 78% and 54%, respectively, using Mn1Co1/CH catalytic ozonation. The
Mn-Co/CH catalyst had a high compressive strength (15.89-16.94 MPa). The
degradation efficiency of hydroquinone decreased significantly after the addition
of tert-butanol, which indicated that.OH played an important role in the
Mn1Co1/CH catalytic ozonation. The catalytic ozonation process fitted the first
order kinetic model. The apparent rate constant k for O3 alone was only 0.0306.
Furthermore, the Mn1Co1/CH catalyst had the highest rate, with an apparent rate
constant k of 0.0535 min-1. The Mn-Co/CH catalyst was easy to industrialize owing
to its lower consumption, excellent catalytic characteristics, and long working
life.
PMID- 29962144
TI - [Degradation Mechanism of Tetracycline Using Fe/Cu Oxides as Heterogeneous
Activators of Peroxymonosulfate].
AB - A green, highly efficient, and porous copper-ferrite heterogeneous catalyst (Fe
Cu-400) with good magnetism was synthesized via a coprecipitation method. The
catalysts were characterized using XRD, BET, FESEM, and EDS. The performance of
Fe-Cu-400 as a catalyst was evaluated by activating peroxymonosulfate (PMS) for
degradation of tetracycline (TC) in aqueous solution and investigating the
influence of several water parameters. The Fe-Cu-400/PMS system showed a greater
TC degradation ability, and the degradation rate of TC was enhanced with an
increase in the PMS concentration and the initial pH of the coupled Fe-Cu-400/PMS
system. Anions including H2PO4-, HCO3-, and Cl- promoted TC degradation, whereas
NO3- showed a low inhibitory influence. In addition, Fe-Cu-400 exhibited
excellent reusability towards activating PMS for TC degradation after five runs
of tests. Possible mechanisms of the activation of PMS by Fe-Cu-400 and the main
reactive species were proposed based on radical identification tests and XPS
analysis. Furthermore, a potential degradation pathway was proposed that included
hydrolysis and sequential removal of N-methyl, hydroxyl, and amine functional
groups according to the results of LC-MS and TOC detections.
PMID- 29962145
TI - [Behavior and Mechanisms of Cd(II) Adsorption from Water by Niobate-Modified
Titanate Nanosheets].
AB - Niobate-modified titanate nanosheets (Nb-TNS) were synthesized through a
hydrothermal method and used to remove Cd(II) from water. TEM and SEM
characterizations indicated that the new nanocomposites were non-curled
nanosheets. XRD showed that the material was composed of sodium tri-titanate and
niobate, and titanate was the primary component. Ion exchange between Cd2+ and
Na+ in the interlayers of the Nb-TNSs was the dominant mechanism for Cd(II)
adsorption, leading to good adsorption performance. The material exhibited rapid
adsorption kinetics for Cd(II), reaching equilibrium within 60 min, and the data
fit well with the pseudo-second order model (R2=1). The maximum adsorption
capacity of Cd(II) was 287.9 mg.g-1, according to the Langmuir isotherm model,
which was larger than that of most of traditional adsorbents. Higher pH promoted
adsorption because the negatively charged material could capture Cd(II) cations
more easily. Co-existing inorganic ions (Na+and Ca2+) were unfavorable to the
adsorption of Cd(II) by Nb-TNS owing to the competition for adsorption sites. In
addition, a slight inhibition effect on the adsorption in the presence of humic
acid (HA) was found. Cd(II) was efficiently desorbed from Nb-TNS after HNO3
treatment, and -ONa sites were restored with NaOH treatment. Considering its
simple synthesis method, high removal efficiency for heavy metals, and good
reusability, Nb-TNS is a promising material for remediation of areas contaminated
by heavy metals.
PMID- 29962146
TI - [Trace Amounts of Phosphorus Removal Based on the in-suit Oxidation Products of
Iron or Manganese in a Biofilter].
AB - In order to remove trace amounts of phosphorus from water bodies, a lab-scale
biofilter was constructed to investigate the capacity of in situ oxidation
products of iron or manganese for phosphorus adsorption. SEM, EDS, BET, and zeta
technologies were employed to reveal the adsorption mechanisms. The results
indicated that phosphorus could be removed by the oxide products generated from
the iron or manganese removal process, at 106.28 MUg.mg-1 and 77.98 MUg.mg-1,
respectively, as shown by the linear relationships between phosphorus removal and
the two oxides. SEM, EDS, and BET analysis demonstrated that the BET specific
surface areas for the iron- and manganese-rich oxides were 96 m2.g-1 and 67 m2.g
1, respectively, with the former accumulated between the pore spaces of the
filtering sand and easily washed out of the layer by backwashing, whereas the
latter coated the surface of the filtering sand. Thus, backwashing was favorable
for phosphorus adsorption in the iron oxidation process to avoid
overaccumulation. Moreover, the zero point of charge of the two oxides indicated
electrostatic attraction may have occurred between iron-rich oxide and
phosphorus; however, inner-sphere complex reactions obviously occurred for the
two oxides because the zero point of charge after phosphorus adsorption decreased
to a lower level. In addition, other anions were negatively complexed with the
phosphorus on the surface of the oxides, it demonstrated that phosphorus
adsorption on the surface of the two oxides seemed to be a specific adsorption.
PMID- 29962147
TI - [Effect of Preparation Methods on Phosphate Adsorption by Iron-Titanium Binary
Oxide: Coprecipitation and Physical Mixing].
AB - To investigate the effect of preparation methods on surface characteristics and
adsorption properties of the formed metal composite oxides, two kinds of iron
titanium binary oxides were synthesized by a coprecipitation method or a physical
mixing method and were denoted as CFe-Ti and MFe-Ti, respectively. The prepared
CFe-Ti and MFe-Ti were systematically characterized using SEM, XRD, BET, and FTIR
techniques. Their phosphate adsorption behaviors were also studied via batch
adsorption experiments. Compared with pure FeOOH and TiO2, CFe-Ti exhibited a
looser nanostructure with more pore and surface hydroxyls. Moreover, the CFe-Ti
had a high maximal phosphorus adsorption capacity of 40.6 mg.g-1, which is about
1.5 times and 2.4 times as high as that of pure FeOOH (27.2 mg.g-1) and TiO2
(16.7 mg.g-1), respectively. This suggests that an obvious synergistic effect is
present in the CFe-Ti system. However, the morphology and structure of MFe-Ti
were not significantly different from those of pure FeOOH and TiO2. The maximal
adsorption capacity of MFe-Ti was 22.7 mg.g-1, which is obviously lower than that
of CFe-Ti and even lower than that of pure FeOOH. Evidently, there is no
synergistic effect in the MFe-Ti system. In addition, phosphate adsorption
mechanisms at the surface of CFe-Ti and MFe-Ti were the same as those of their
component oxides, and chemical adsorption occurred at the surface of the oxides
through the formation of inner-sphere complexes. Therefore, the surface
characteristics and adsorption properties of the metal composite oxides were
closely related to their preparation methods. The coprecipitation method was a
simpler and more economical way than the physical mixing method to fabricate a
highly effective iron-titanium binary oxide for phosphate adsorption.
PMID- 29962148
TI - [Effects of Conductivity on Performance of a Combined System of Anaerobic
Acidification, Forward Osmosis, and a Microbial Fuel Cell].
AB - In this study, a novel combined system for simultaneous recovery of
bioelectricity and water from wastewater was developed by integrating anaerobic
acidification and a forward osmosis (FO) membrane with a microbial fuel cell
(AAFO-MFC). Conductivity was thought to be an important factor affecting the
performance of the AAFO-MFC system. Thus, effects of conductivity on the
performance of AAFO-MFC system in treating synthetic wastewater were
investigated. The results indicated that a higher conductivity increased the
bioelectricity production, owing to a reduction in the internal resistance.
However, it resulted in a rapid decrease of FO water flux and a shorter operating
time because of a severer membrane fouling. The conductivity had no impact on the
water quality of the effluents. The total organic carbon (TOC) and total
phosphorus (TP) concentrations in the FO permeate were less than 4 and 0.5 mg.L
1, respectively, at all conductivity levels. However, the rejection of the FO
membrane for NH4+-N was lower at all conductivity levels. The optimal
comprehensive performance of this system was obtained when the conductivity was
maintained at 7-8 mS.cm-1. In this case, the AAFO-MFC system achieved continuous
and relatively stable power generation, and the water flux of FO membrane was
relatively stable during a long-term operation of approximately 29 days.
PMID- 29962149
TI - [COD Requirement for Biological Phosphorus Removal Granule System Under Different
Phosphorus Concentrations].
AB - In this study, the effect of COD loading on a biological phosphorus removal
granule system under different phosphorus concentrations was investigated by
changing the concentration of total phosphorus (TP) and COD in the influent. The
lowest concentration of COD for good performance of the biological phosphorus
removal system under different phosphorus concentrations was obtained. The
results show that when the concentration of TP was 10 mg.L-1 in the influent, the
lowest concentration of COD for good performance of the biological phosphorus
removal system was 175 mg.L-1. The concentration of TP in the effluent was below
0.5 mg.L-1; the particle size and SVI were 1020 MUm and 36 mL.g-1, respectively;
and the contents of PN and PS (by MLSS) were 78 mg.g-1 and 39 mg.g-1,
respectively. Furthermore, the PN/PS was lower and the granules had good
structure and performance. When the concentration of TP was 6 mg.L-1 in the
influent, the lowest concentration of COD for good performance of the biological
phosphorus removal system was 150 mg.L-1. The concentration of TP in the effluent
was below 0.3 mg.L-1; the particle size and SVI were respectively 960 MUm and 35
mL.g-1; and the contents of PN and PS were 75 mg.g-1 and 35 mg.g-1, respectively.
Moreover, the PN/PS was lower and the granules had good structure and
performance. The removal efficiency of COD was above 83% and the concentration of
COD in the effluent was below 25 mg.L-1 throughout the operational process. Under
different the influent phosphorus concentrations, the contents of PN and PS
decreased, PN/PS increased, particle size decreased, SVI increased, and the
structure and performance of the biological phosphorus removal granules
deteriorated as the COD concentration decreased.
PMID- 29962150
TI - [Effect of Substrate Concentration on SAD Collaborative Nitrogen and Carbon
Removal Efficiency in an ABR Reactor].
AB - In order to solve the problem of declining total nitrogen (TN) removal caused by
anaerobic ammonium oxidation (ANAMMOX) and the suppression of organic matter for
ANAMMOX, the anaerobic baffled reactor (ABR), inoculating ANAMMOX sludge and
anaerobic sludge from a municipal WWTP, was selected to construct system of
ANAMMOX coupled denitrification (SAD) by the control of different substrate
concentration. The SAD was constructed to study the effects of different influent
substrates (COD, NO2--N, NH4+-N) on the performance of nitrogen and carbon
removal in the coupled system and pollutant removal rules. The results showed
that the coupling reaction was achieved in the ABR reactor and the inhibitory
effect of organic compounds on anaerobic ammonium oxidation bacteria (AAOB) was
relieved. When influent concentrations of COD, NO2--N, and NH4+-N were 260, 185,
and 100 mg.L-1, respectively, which equates to a ratio of 2.6?1.85?1, the
concentrations of these substances in the effluent decreased to 10, 1.0, and 0.9
mg.L-1, respectively. The TN removal rate reached 99%, hence stable system
operation and ultra-low emissions of carbon and nitrogen pollutants were
achieved. Under different conditions of substrate concentrations and ratios, the
targeted pollutants were generally eliminated in the first compartment, in which
the removal rate reached higher than 75%, and ANAMMOX held the dominant position
in the SAD coupled system.
PMID- 29962151
TI - [Evaluation of Advanced Nitrogen Removal from Coking Wastewater Using Sulfide
Iron-containing Sludge as a Denitrification Electron Donor].
AB - In general, it is difficult to reach the total nitrogen discharge standard in the
effluent after municipal and industrial wastewater treatment. The problems
hindering advanced denitrification include an unstable C/N ratio in the influent
wastewater, increased hydraulic loading with increasing reflux ratio, reduced
reaction kinetics, high energy consumption, and secondary pollution and high
sludge yield resulting from addition of organic carbon sources. Therefore, deep
denitrification with the advantages of energy savings and easy operation is
urgently needed. To address these issues, chemical iron sulfide sludge, collected
after the pretreatment of sulfur-containing industrial wastewater, was used as a
solid-phase electron donor to perform advanced denitrification using autotrophic
denitrifiers. In this study, the secondary biological effluent of coking
wastewater was the influent for denitrification and the performance of
denitrification, transformation of sulfide and iron in the sludge, and microbial
community changes were investigated. The optimal reaction conditions and effect
range of the technology for deep denitrification of wastewater were then
calculated. When the concentrations of NO3--N and NO2--N in the influent were
(74.54+/-0.57) and (1.11+/-0.19) mg.L-1, respectively, the corresponding
concentrations in the effluent were reduced to (2.78+/-1.08) and (2.87+/-0.71)
mg.L-1, respectively, with a hydraulic retention time (HRT) of 18 h. The removal
rate of TON (NO3--N+NO2--N) was as high as 90.0%, of which the reduction rate of
NO3--N and the accumulation rate of NO2--N were 12.06 and 7.74 mmol.(L.d)-1,
respectively. This study showed that the use of chemical sulfide iron sludge as
an electron donor for deep denitrification is of practical importance, as it
could simplify the subsequent treatment of sulfur- and iron-rich chemical sludge,
finally reaching the goal of resource utilization.
PMID- 29962152
TI - [Stability of Nitritation Combined with Limited Filamentous Bulking Under
Intermittent Aeration].
AB - Limited filamentous bulking (LFB) combined with nitritation under low dissolved
oxygen (DO) is a new technology for enhancing nitrogen removal and reducing
aeration requirements. In order to investigate the feasibility and sustainability
of this technology, two sequence batch reactors (SBRs) were operated under
different regimes to stimulate different aeration modes under low DO (0.3-0.8
mg.L-1). Sludge settleability, nitrite accumulation ratio (NAR), total nitrogen
(TN) removal rate, dynamic variation of dominant filaments, and nitrifying
bacterial communities were investigated. The results indicated that short-cut
nitrification combined with LFB could be achieved under intermittent aeration,
and the ratio of anoxic/aerobic was 15 min/30 min, the value of sludge volume
index (SVI) was maintained from 170 mL.g-1 to 200 mL.g-1. An NAR above 95% was
achieved under real-time continuous aeration. Meanwhile, LFB was induced when
nitrite started to accumulate, and the dominant filament was Type 0092. However,
the limited bulking was not maintained for the long term. After a transfer from
continuous aeration to intermittent aeration, LFB reappeared in 60 days and the
value of SVI remained between 170 mL.g-1 and 200 mL.g-1. The process of
nitritation combined with LFB was maintained stably for the next two months, and
the TN removal rate was above 66%. FISH analysis indicated that the identical
dominant filaments were M. parvicella and Type 0092 for maintaining limited
bulking in the two reactors. qPCR results showed that proportion of AOB in the
total bacteria increased from the previous 0.53% to 2.19% in the end, whereas
that of NOB decreased from 17.5% to 3.2% in SBR A. Moreover, the proportion of
AOB increased from 0.51% to 1.53%, whereas that of NOB decreased from 18.05% to
11.01% in SBR B.
PMID- 29962153
TI - [Filamentous Sludge Microbial Community of a SBR Reactor Based on High-throughput
Sequencing].
AB - Samples were collected from a sequencing batch reactor (SBR) to characterize the
similarities and differences in microbial community composition in samples using
Illumina high-throughput sequencing. The main objective of this study was to
characterize changes in microbial community composition during filamentous sludge
bulking and control processes. The SBR working volume was 11 L, and the reactors
were operated for 399 days in total. High-throughput sequencing results indicated
that rich diversity existed in the microbial communities of the seeding sludge.
Generally, during sludge bulking, microbial composition decreased, and after the
sludge was remediated, the diversity gradually increased. The dominant bacteria
in the seeding sludge were Saprospiraceae_norank, Comamonadaceae_unclassified,
and Tetrasphaera, comprising 13.37%, 10.54%, and 8.59% of the community,
respectively. After culturing using sodium acetate as the sole carbon source,
Thiothrix and Trichosporon increased significantly from the seeding to the
bulking sludge, with ranges from 0.1% to 60.14% and from 19.60% to 94.82%,
respectively. After the sludge bulking was controlled, the relative abundances of
Thiothrix and Trichosporon were 0.1% and 2.32%, respectively. Therefore, we
postulate that increases in filamentous Thiothrix and Trichosporon were the main
cause for the sludge bulking.
PMID- 29962154
TI - [Impact of Nano Zero-Valent Iron (NZVI) on Methanogenic Activity, Physiological
Traits, and Microbial Community Structure in Anaerobic Digestion].
AB - Effects of short-term nano zero-valent iron (NZVI) and zero-valent iron (ZVI)
exposure on methanogenic activity of anaerobic sludge, physiological traits,
composition of phospholipid fatty acids (PLFA), and microbial community structure
were investigated. Results show that accumulated methane production decreased
with an increase of NZVI concentration; yet, methane production only changed
slightly with the same concentration of ZVI. In the NZVI (100-5000 mg.L-1) sets,
dissolved iron (DFe) concentrations were 1.6-7.4 times that of the control value
at 5 d, whereas DFe was only slightly above the control in the ZVI set (5000 mg.L
1). The concentration of extracellular polymeric substances and cell viability
decreased to 21.1% and 79.7%, respectively, of the control in the 5000 mg.L-1
NZVI treatments. Coenzyme F420 and coenzyme M decreased to 40.2% and 61.1%,
respectively, of the control in the 5000 mg.L-1 NZVI treatments, which were
significantly increased to 1.3 times that of the control value in the 100 mg.L-1
NZVI and 5000 mg.L-1 ZVI treatments. The order of unsaturation and branch PLFA
content was ZVI-5000 (21.18%) > control (19.37%) > NZVI-1000 (16.69%) > NZVI-5000
(15.94%) > NZVI-100 (12.08%). High NZVI concentration (5000 mg.L-1) resulted in
an increase of DFe and a decrease of cell membrane fluidity and key coenzyme
activity of methanogenesis, which led to the inhibition of methane production.
Principle component analysis and redundancy analysis indicated that differences
in the microbial community existed among these treatments and that Nakamurella,
Bacillus, Trichococcus, and Petrimonas showed tolerance to NZVI.
PMID- 29962155
TI - [Effects of Gas/Water Ratio on the Characteristics of Nitrogen Removal and the
Microbial Community in Post Solid-Phase Denitrification Biofilter Process].
AB - To solve the problems of high-energy consumption, complex processes, and low
nitrogen removal efficiency in the currently available low carbon source
wastewater treatment processes, a novel coagulation sedimentation/post solid
phase denitrification biofilter process (CS-BAF-SPDB) was proposed. The effect of
gas/water ratio on nitrogen removal efficiency of the CS-BAF-SPDB was studied.
The changes in the microbial community structure along the varying gas/water
ratio were investigated, and the functional bacteria were identified using
polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). The
results showed that, to realize favorable nitrifying and denitrifying performance
simultaneously in the BAF-SPDB unit, the gas/water ratio of the BAF should be set
at 4?1. In addition, the influence of the macro operational parameters on the
performance of the BAF and SPDB had a direct relationship with the dynamic
changes in the micro microbial community. The influence of gas/water ratio on
nitrification performance in the BAF was mainly embodied in the changes of
composition, amount, and activity of ammonia-oxidizing bacteria Candidatus and
Nitrospira defluvii and nitrite-oxidizing bacteria Nitrosomonas sp. Nm47, whereas
that on denitrification performance in the SPDB was mainly embodied in the
changes of composition and amount of solid carbon substrate degrading
denitrifying bacteria Pseudomonas sp. and Myxobacterium AT3-03 and heterotrophic
denitrifying bacteria Dechloromonas agitate, Comamonas granuli, and Rubrivivax
gelatinosus.
PMID- 29962156
TI - [Comparison of Extraction Methods of Extracellular Polymeric Substances from
Activated Sludge].
AB - Extracellular polymeric substances (EPSs) are biosynthetic polymers of microbial
origin in the sludge activation process and crucially affect the properties of
sludge in biological wastewater treatment reactors, such as the formation of
sludge flocs, stabilization of sludge structure, and protection of microbes
against noxious environmental conditions. However, the EPS extraction efficiency
differs significantly according to the extraction method used. In this study,
soluble EPSs and loosely bound EPSs can be extracted by centrifugation first and
tightly bound EPSs in activated sludge require additional eight treatments for
extraction, respectively. Three physical methods (centrifugation, sonication, and
heating) and five chemical methods (cation exchange resin, NaOH,
formaldehyde+NaOH, EDTA, and formaldehyde+EDTA) were tested, and the content and
composition of TB-EPS were analyzed. Meanwhile, the functional groups and
elements in TB-EPS were investigated. Results showed that the heating method did
not introduce exogenous substances during the EPS extraction process and that the
destruction of cells from this method was relatively slight. Heating was shown to
be a gentle and efficient method in this study. The three-dimensional excitation
and emission matrix (EEM) fluorescence spectroscopy showed that the cation
exchange resin method had good extraction effect on humic-like and protein-like
substances. As to fulvic-acid-like substances, NaOH was better than the other
seven methods. Infrared spectroscopy showed that no notable difference appeared
in the functional groups of the TB-EPS extracted by physical methods, whereas
chemical methods induced big differences and showed particular bands that did not
appear in the TB-EPS extracted by physical methods. Overall, the amounts of TB
EPS elements extracted using chemical methods were greater than those extracted
using physical methods. In conclusion, a method must be selected and established
for each case, taking into consideration the experimental purpose, and the most
appropriate method should be chosen carefully.
PMID- 29962157
TI - [Identification and Characterization of a Hypothermic Alkaliphilic Aerobic
Denitrifying Bacterium Pseudomonas monteilii Strain H97].
AB - Low temperatures and high pH generally inhibit bio-denitrification. Thus, it is
important to explore psychrotrophic and alkali-resistant microorganisms for
nitrogen degradation. This study mainly focused on the identification of an
alkaliphilic strain and preliminary exploration of its denitrification
characteristics. Based on morphological observations, phospholipid fatty acids
and 16S rRNA gene sequence analysis, strain H97, which was isolated from the
winter paddy field in Guizhou province, was identified as Pseudomonas monteilii.
Till date, there were few reports about the denitrification characteristics of
Pseudomonas monteilii. The effects of environmental factors such as temperature,
inoculation quantity, C/N ratio, initial pH, and carbon source were investigated
using simulated wastewater. The optimum conditions for nitrate and total nitrogen
removal by H97 were: inoculum size 1.5*106 CFU.(100 mL)-1; initial pH 9.0;
C/N=15; 15C; and sodium succinate as the carbon source. The nitrate and total
nitrogen removal efficiencies were 97.69% and 96.32%, respectively, at optimum
conditions with an initial nitrate nitrogen concentration of 50.0 mg.L-1. The
temperature experiments indicated that the optimal temperature for highest
nitrogen removal efficiency was 15C, and that the strain H97 could survive in a
wide range of 15-40C. Additionally, the nitrate and total nitrogen efficiencies
at the initial pH value of 7.0-11.0 were 91.21% and 79.10%, respectively, and the
denitrification capacity then decreased to 64.75% at the initial pH 12.0. These
results indicated that strain H97 showed cold and alkali resistance, which
suggests an application potential for the treatment of alkaline nitrogen polluted
water in the southern winter.
PMID- 29962158
TI - [Isolation, Identification, and Biodegradation Behaviors of a Perfluorooctane
Sulfonic Acid Precursor (PreFOSs) Degrading Bacterium from Contaminated Soil].
AB - Transformation of perfluorooctane sulfonate (PFOS) precursors (PreFOSs) is
considered an additional source of PFOS in the environment and biota. A PreFOSs
degrading bacterium PF1, which was able to utilize PreFOSs as the sole carbon and
energy source for growth, was isolated from contaminated soil collected from the
surroundings of a fluoride factory. According to its morphology and 16S rDNA gene
sequence analysis, strain PF1 was identified as Hyphomicrobium sp. The
degradation rates of perfluorooctane sulfonamide (PFOSA) and N-ethyl
perfluorooctane sulfonamide (N-EtFOSA) by PF1 were 14.6% and 8.2% (30C; pH=7.0
7.2), respectively, whereas PF1 was unable to degrade PFOS. PFOSA could be
biodegraded to PFOS. N-EtFOSA could be biodegraded to perfluorooctane sulfonamide
acetic acid (FOSAA), PFOSA, and PFOS; PFOS was the predominant metabolite. Based
on the above analysis, the proposed metabolic pathway of PFOSA by strain PF1 is
deamination to form PFOS. Two possible degradation pathways are proposed for N
EtFOSA: 1 deethylation of N-EtFOSA to produce PFOSA, followed by deamination to
form PFOS, and 2oxidation of N-EtFOSA to FOSAA followed by sequential
dealkylation to produce PFOSA, and then transformation to PFOS by deamination.
PMID- 29962159
TI - [Microbial Community Distributions in Soils of an Oil Exploitation Site].
AB - To design a reasonable and effective remediation scheme for soil in contaminated
sites, it is necessary to understand the microbial communities in the soil.
Samples were collected at different depths (0 cm to 400 cm) in four locations:
one that was persistently contaminated and near an oil well, one that was
historically contaminated in the middle of the site, one in a mud pit, and one in
farmland. High-throughput sequencing of the V4 region of 16S rRNA in these
samples was performed. In addition to physico-chemical properties of the soil,
the alpha-diversity, species composition, and differences in species between
groups of microorganisms were analyzed, and a principal coordinate analysis and
canonical correlation analysis were conducted. Results showed that oil and salt
contents in soils were the dominant factors affecting microbial community
structure. Hydrocarbon-degrading microorganisms were abundant in oil-contaminated
soils, whereas halophilic hydrocarbon-degrading microorganisms were present in
soils with high salt contents. Therefore, hydrocarbon-degrading microorganisms
might be useful in remediation of oil-contaminated sites.
PMID- 29962160
TI - [Characteristics of Soil Physicochemical Properties and Enzyme Activities over
Different Reclaimed Years in a Copper Tailings Dam].
AB - Mining for metal and mineral resources lead to the rapid rise of tailings dams
and caused serious damage to the ecological environment of the mining area. Soil
physicochemical characteristics and enzyme activities were important indexes for
ecosystem functions, and they were also important factors in evaluating soil
restoration qualities. We selected nine sub-dams of the Eighteen River copper
tailings in Yuanqu County, and analyzed the relationship between soil
physicochemical properties and soil enzyme activities. The results showed that
there were great differences in soil physicochemical properties over different
reclaimed years, and as the reclaimed years passed, soil nutrient contents
significantly increased. There were significant negative correlations between
catalase and the ratio of soil carbon and nitrogen, and urease was positively
correlated to total nitrogen and soil moisture. Phosphatase and sucrose
demonstrated no significant relationships with soil physicochemical factors.
Copper content gradually accumulated in soil as the restoration period of sub
dams increased. Arsenic and cadmium content increased initially and then
decreased before they gradually reached a stable level. In addition, there was no
significant difference in zinc content among different sub-dams. Together, these
results provide the ecological basis for further studies in soil ecosystem
restoration and degradation mechanisms in copper tailings.
PMID- 29962161
TI - [Risk Analysis of Heavy Metal Contamination in Farmland Soil Around a Bauxite
Residue Disposal Area in Guangxi].
AB - Bauxite residue disposal areas (BRDA) appear to result in the heavy metal
pollution of the farm fields surrounding them. In total, 194 topsoil samples were
collected from the fields surrounding a BRDA in Guangxi in order to
comprehensively understand the pollutant characteristics. These characteristics
and their ecological risks were assessed by the Nemerow and Harkanson indices,
whilst the sources and correlations of eight heavy metals (V, Cr, Ni, Cu, Zn, As,
Pb, and Co) were analyzed by means of the spatial interpolation method,
correlation analysis, and principal component analysis (PCA). The results
demonstrated that the surrounding fields were seriously polluted by heavy metals.
Ninety-two percent of samples were polluted, including 36% that showed serious
pollution, and As was the dominant contaminant. The ecological risk results
showed that the risks of the surrounding fields were medium, and As was
responsible for 68% of this. Spatial interpolation suggested that concentrations
of heavy metals in the northeastward and southwestward areas were higher, however
the southeastward areas were lower. Multivariate statistics indicated that the
possible source of As contaminant was different to those of V, Ni, Zn, Pb, and
Co; As was primarily influenced by anthropogenic contamination, including
atmospheric sedimentation, and agricultural fertilization. Cr was affected by
both soil parent material and atmospheric sedimentation, whereas V, Ni, Zn, Pb,
And Co levels were mainly affected by soil parent material.
PMID- 29962162
TI - [Occurrence and Distribution of Phthalate Esters in Urban Soils of Chongqing
City].
AB - In total, 66 soil samples were collected from five different urban functional
areas in Chongqing, and the concentration levels of phthalate esters (PAEs) were
analyzed using ultra-high performance liquid chromatography-quadrupole time-of
flight mass spectrometry (UPLC-Q-TOF-MS). Meanwhile, the composition and
characteristics of PAEs were discussed, along with their possible sources,
through correlation analysis and principal component analysis. The results showed
that the concentrations of ?PAEs ranged from 93.1-312 ng.g-1 dry weight, which is
at the low end of the worldwide figure. DEHP, DBP, and DIBP were the dominant
compounds, contributing 87.4%-92.9% of the total ?PAEs. DEHP was the most
abundant PAE congener, responsible for 52.4% of the total ?PAEs. Through
correlation analysis, it was noted that PAEs with similar molecular weight were
more likely to show a significant relationship with each other, which suggested
that these PAEs may share a similar source. According to the principal component
analysis, DBP, DIBP, and DEHP had a similar source, while BBP and DnOP strongly
correlated with each other. Compared to other studies, relatively low PAE
concentrations were apparently observed in this study, but the potential human
risk via exposure to these compounds should also been considered.
PMID- 29962163
TI - [Profile Distribution of Paddy Soil Organic Carbon and Its Influencing Factors in
Chengdu Plain].
AB - Understanding the effects of environmental factors on the profile distribution of
soil organic carbon (SOC) is a base to accurately modeling the continuous change
of SOC in vertical and three-dimensional spatial distributions, as well as
precisely estimating SOC storage. Based on 171 soil profiles collected from
Chengdu Plain, the effects of environmental factors (including the parent
material, soil type, elevation, distance from river, and land use) on the profile
distribution of paddy SOC to a depth of 1 m were evaluated through the
exponential decay function. The results indicated that SOC was estimated at
19.42, 9.59, 5.99, and 5.20 g.kg-1 at depths of 0-20, 20-40, 40-60, and 60-100cm,
respectively, showing a significant decrease with increased depth. Soil organic
carbon was mainly concentrated above a 40 cm soil depth, accounting for 72.17% of
the total profile, which could be crucial to studying the carbon source/sink of
paddy soils in Chengdu Plain. The parameters of the exponential decay function
had a similar spatial pattern, indicating their spatial dependence. The nugget
coefficients for C and k were 55.400% and 47.671%, respectively, indicating that
paddy SOC in the study area was affected by both structural and random factors.
Regression analysis implied that the parent material and soil genius were the
dominant factors influencing the profile distribution of SOC. Nevertheless,
elevation, distance from river, and land use should also be taken into
consideration. It has been concluded that the parent material and soil genius
should be premeditated when fitting the vertical distribution of SOC, modeling
the three-dimensional prediction of soil organic carbon, and estimating soil
carbon storage in the paddy soils of Chengdu Plain.
PMID- 29962164
TI - [Correlation Between Soil Organic and Inorganic Carbon and Environmental Factors
in Cotton Fields in Different Continuous Cropping Years in the Oasis of the
Northern Tarim Basin].
AB - Studying the characteristics of soil organic carbon (SOC) and soil inorganic
carbon (SIC), and their relationship with environmental factors is helpful for
understanding soil ecological processes, and providing theoretical support for
research on the global carbon budget. Based on the oasis in the northern margin
of Tarim Basin, this study analyzed the characteristics of the soil carbon pool,
and, combined with redundancy and path analyses, explored the relationship
between SOC and SIC, and their environmental factors. The results showed that
there was a significant difference (P<0.05) in SOC and SIC contents in cotton
fields with different continuous cropping years (P<0.05). With an increase in
continuous cropping years, the SOC content increased firstly and then decreased,
while the SIC content decreased firstly and then increased (P<0.05). The SOC
content was the highest in the 0-20 cm layer, while the SIC content was the
highest in the 20-50 cm layer. The importance of environmental factors on the
characteristics of the soil carbon pool was deduced by redundancy analysis. The
order of importance was phosphatase activity > pH > sucrase activity > catalase
activity > total N > available P > available K > soil moisture content > urease
activity > electrical conductivity (EC); phosphatase activity, pH value,
invertase activity, catalase activity, total nitrogen, available phosphorus, and
available potassium showed significant correlation with SOC and SIC (P<0.01).
Soil moisture and urease activity showed significant correlation with SOC and SIC
(P<0.05). The path analysis showed that available P had a direct effect on the
SOC content; it was the main factor affecting it. The urease activity had a
direct effect on SIC; it was the main factor affecting it. This study of soil
carbon pools in arid and semiarid regions is the basis for evaluating the
"source/sink" effect of soil carbon in farmland ecosystems, and is of great
significance for studying the global carbon budget and land carbon cycle
mechanism.
PMID- 29962165
TI - [Soil Organic Carbon Components and Their Correlation with Soil Physicochemical
Factors in Four Different Land Use Types of the Northern Tarim Basin].
AB - In order to clarify the distribution of each component of soil organic carbon
(SOC) in arid areas, and to develop methods to rationally solve problems caused
by inefficient land use and blind tillage, we studied the effects of different
land use patterns on the SOC, microbial biomass carbon (MBC), dissolved organic
carbon carbon (DOC), and easily oxidized organic carbon (EOC) on four different
land use types: saline soil, natural forest, sandy land, and 30 a cotton field in
the northern Tarim Basin. The relationships between different carbon components
and soil physicochemical factors were researched by redundancy analysis (RDA).
The results showed that the SOC showed the highest value (1.92 g.kg-1) in natural
forests and increased with soil depth, while the other land use types showed a
downward trend as a whole. The MBC showed the highest level in natural forests,
and decreased with soil depth, but there was no obvious change trends in other
land use types. The highest and lowest DOC contents appeared in the 80-100 cm
layer (143.23 mg.kg-1 and 30.00 mg.kg-1, respectively) in the natural forest and
30 a cotton field, respectively, and increased with soil depth in the natural
forest (P<0.05). In the saline soil, the DOC content of the soil decreased with
increased depth, and the contents of different soil layers showed significant
differences (P<0.05). The EOC content did not show a obvious regularity in
different soil layers of different land use types. Sensitivity analysis of each
organic carbon component showed that the MBC was the most sensitive to soil layer
changes, and the DOC was the most sensitive to different land use patterns. The
MBC has a certain indication of soil layer change, which may be due to the fact
that microbial biomass C in different layers has different living environments,
so the content was significantly different. The DOC has a certain indication of
land use types change, which may be due to the adaptation to different
situations. Through the RDA, it was found that there was a positive correlation
between soil components and soil water content (SWC), total nitrogen (TN) and pH,
and a negative relationship between bulk density (BD) and electrical conductivity
(EC). The order of importance of environmental factors to the contents of carbon
components is as follows: BD > SWC > EC > TN > pH. This indicates that bulk
density and water content are the main factors affecting organic carbon
components in arid regions.
PMID- 29962166
TI - [Short-term Mechanism of Warming-induced Stability for Organic Carbon in the
Karst Plateau Soil].
AB - Elucidating the mechanisms of warming-induced stability for soil organic C is one
of the keys for evaluating the tendency of soil C sources/sinks in projected
global warming models. Organic C densities in soil, and soil physical and
biochemical fractions, under different warming scenarios in the Karst Plateau
were investigated following a 4-yr continuous warming using infrared radiators,
via density fractionation and acid hydrolysis. Six treatments were arranged: no
warming (ambient temp, CK); symmetric warming (ambient+2.0C full year); and
lowly, moderately, highly, and extremely asymmetric warming (ambient+2.5C/1.5C,
3.0C/1.0C, 3.5C/0.5C, and 4.0C/0C in winter-spring/summer-autumn seasons,
respectively; LAW, MAW, HAW, and EAW). The moderately asymmetric warming was
highly similar to a multi-year warming scenario in the study region. The results
showed there were no significant differences in soil organic C densities in the
surface layer (0-15 cm) among the warming treatments, with a range of 1.95 kg.m-2
to 2.02 kg.m-2, which is insignificantly different to the CK (1.94 kg.m-2). There
were no significant differences in the C density of light and heavy fractions,
and the recalcitrant heavy-fraction among the warming treatments, and between the
warming and no warming treatments. The average recalcitrant C density of the
light fraction in the warming treatments was 1.18 times higher than the CK, with
a significantly higher recalcitrant C density of the light fraction in the
symmetric warming, and lowly and moderately asymmetric warming treatments,
compared to that of the CK. The recalcitrant C density and recalcitrant C index
of the light fraction showed a tendency to decrease as the asymmetry of warming
increased under the five warming scenarios. Warming had negligible effects on the
organic C density in soil, and soil physical and biochemical fractions in the
subsurface layer (15-30 cm). The results revealed that in the short-term, warming
may increase the recalcitrance of non-protected C in the Karst Plateau soil. This
is not necessarily an over- or underestimation of the effects of global warming
on soil organic C density and the capacity of soil to protect C when subjected to
symmetric warming, but may potentially overestimate the recalcitrance of organic
C in the non-protected fraction of the surface layer (0-15 cm).
PMID- 29962167
TI - [Effects of Boron Treatment on Arsenic Uptake and Efflux in Rice Seedlings].
AB - The impacts of boron (B) root application and foliar spray on arsenic (As)
uptake, translocation, and efflux by/in rice seedlings (Oryza sativa L.) were
investigated in three hydroponic experiments. The addition of B to culture medium
did not alter concentrations of arsenite (As[III]), arsenate (As[V]), and total
As, nor did it alter transfer coefficients or uptake efficiency of As in rice
seedlings under either As(III) or As(V) exposure. Foliar B supply increased shoot
B concentrations 15.8-fold, and decreased root As concentrations and As uptake
efficiency by 20.9% and 18.0% under As(V) treatment, and by 12.6% and 13.8% under
As(III) treatment, respectively, yet did not significantly decrease shoot As
concentrations (P>0.05). Interestingly, foliar B supply reduced root B
concentrations by up to 47.1% under exposure to As(V) but not As(III), and
corresponding root B concentrations were 85.3% higher in As(V) treatment than in
As(III) treatment on average (P<0.05). Both total As and As(V) concentrations
were positively related to B concentration in rice roots under As(V) treatment
following foliar B supply (P<0.05). Rice seedlings extruded 105.2% more As after
As(III)-pretreatment than after As(V)-pretreatment. Foliar B supply increased the
amount of As excreted by As(III)-pretreated rice root by 14.0%-16.9% (P>0.05),
and had no effect on the As efflux of As(V)-pretreatment seedlings. A range of
45.9%-70.7% of root As was excreted to solution during one week. These results
indicate that the root application of B at four times the concentration of As can
slightly decrease As accumulation by rice, whereas foliar B supply is conducive
to a decline in As acquisition by rice roots. It is likely that the B channel is
at least not the main pathway for As(III) entering into rice roots, and the As(V)
distribution mechanism in rice plants may be shared with that of B.
PMID- 29962169
TI - [Seasonal Variation in Surface Ozone and Its Effect on the Winter Wheat and Rice
in Nanjing, China].
AB - In recent years, surface ozone concentration has been increasing. A high
concentration of ozone can affect the growth of crops, and reduce crop yields. In
this paper, based on hourly ozone concentration data in the Nanjing area obtained
from 2014 to 2016, we analyzed the variation characteristic of ozone
concentration and its effect on the production and economic loss of winter wheat
and rice. The results shows that the mean concentrations of ozone in 2014, 2015,
and 2016 were 62.9, 68.6 and 69.1 MUg.m-3, respectively; the ozone concentration
and the number of days exceeding the standard gradually increased each year. The
order (high to low) of seasonal average ozone concentrations was summer, spring,
autumn, and winter. The diurnal variation of ozone concentration in the four
seasons showed a single-peak curve, with the peak and valley ozone values
appearing at 15:00-16:00 and 07:00-08:00, respectively. The accumulated ozone
exposure over a threshold of 40 ppb (AOT40) values during the growing season of
winter wheat in 2014, 2015, and 2016 were 10.5, 14.4, and 9.4 MUL.L-1.h,
respectively. The ozone AOT40 values during the growing season of rice in 2014,
2015, and 2016 were 8.5, 20.0, and 25.6 MUL.L-1.h, respectively. At the current
ozone level, the impact of surface ozone on winter wheat is higher than that on
rice; the range of ozone effect on the yield loss rate of winter wheat was 21.4%
32.8%, and the annual economic loss amounted to 150.766-277.996 million Yuan RMB.
The range of ozone effect on the yield loss rate of rice was 8.1%-24.3%, and the
annual economic loss amounted to 197.472-680.757 million Yuan RMB.
PMID- 29962168
TI - [Comparative Analysis of Different Soil Amendment Treatments on Rice Heavy Metal
Accumulation and Yield Effect in Pb and Cd Contaminated Farmland].
AB - Using selected sepiolite (SEP) and biochar (BC) as contrasts, we investigated the
effects of a new cross-linked modified chitin (CC) on the bioavailability of Pb
and Cd in soils, the yield of rice, and the absorption and accumulation of Pb and
Cd in different parts of rice plants in a field environment. We hope this study
provides the basis for the application of this material to improve soil
fertility, and a direction for further soil improvement studies. A field
experiment was carried out in 2015-2016 on selected Pb- and Cd-contaminated rice
fields in Linghai, Liaoning. The changes in soil pH and available Pb and Cd in
the soil were analyzed after the rice was harvested(October 2016). The effects of
different treatments on the growth traits and yield of rice, the absorption of Pb
and Cd by rice roots, stems and leaves, and grains were compared. The results
showed that adding 167-333 kg.hm-2 CC could increase the soil pH value by 0.36
0.45 units, decreasing the contents of available Pb and Cd in the soil by 46.39%
64.01% and 29.73%-43.24% respectively (P<0.05). This treatment significantly
reduced the Pb and Cd contents in all parts of rice (P<0.05) compared to
conventional fertilization; Pb and Cd contents in different parts of rice were
significantly reduced (P<0.05) by 16.09%-38.14% and 21.22%-31.38% in the root,
19.17%-46.92% and 25.66%-45.34% in the stem and leaf, and 29.47%-58.25% and
44.75%-64.02% in the grain, respectively. The treatment of adding 333 kg.hm-2 CC
(CC-2) reduced the contents of Pb and Cd in rice grains to 0.2041+/-0.011 mg.kg-1
and 0.1922+/-0.021 mg.kg-1, respectively, which were lower than or close to the
limit values of Pb and Cd in rice (0.20 mg.kg-1) as per GB 2762-2005. Compared to
conventional fertilization, SEP treatment, and BC treatment, without adding any
amendments, the yield per mu of rice under CC treatment increased by 33.6-47,
27.6-44, and 8.67-34.77 kg, respectively. The effect of CC-2 treatment on yield
was the most obvious; the yield of rice per mu increased by 47 kg, and the yield
increase rate was 8.59%. The ability of CC to repair soil contaminated by Pb and
Cd and to reduce the contents of Pb and Cd in rice was not weaker than that of
SEP and BC. The CC treatment also controlled the migration and redistribution of
Pb and Cd in soil-rice systems, and significantly increased the yield of rice. It
has good potential to ensure the safe production of rice.
PMID- 29962170
TI - [Hair Mercury Concentrations in Residents of Fuling and Zhongxian in the Three
Gorges Reservoir Region and Their Influence Factors].
AB - To evaluate the mercury (Hg) exposure risk for residents of the Three Gorges
Reservoir Region (TGRR), hair samples were collected from 238 local residents
within the central regions of the TGRR (Fuling District and Zhongxian County) in
this study. Subsequently, total mercury (THg) and methylmercury (MeHg)
concentrations were determined. The results obtained showed that the average THg
and MeHg concentrations in hair samples of the residents within these two areas
were (0.50+/-0.54) MUg.g-1 and(0.35+/-0.25) MUg.g-1, respectively. Specifically,
the average THg and MeHg concentrations in hair samples of Fuling residents
were(0.71+/-0.87) MUg.g-1 and(0.53+/-0.46) MUg.g-1, respectively. Both these
values were higher than those in hair samples of Zhongxian County residents
[THg(0.41+/-0.36) MUg.g-1 and MeHg (0.28+/-0.26) MUg.g-1]. It is noteworthy that
the hair Hg levels in residents of these two areas are both well below the U.S.
Environmental Protection Agency's reference dose (1 MUg.g-1). Hair Hg levels
varied slightly among different age groups; higher Hg levels were detected in
residents in the age group of 40-50 years(P<0.05). However, there was no
significant difference between the hair Hg levels among genders(P>0.05). Hair Hg
levels in females were slightly above those in males. Hair Hg levels were
significantly correlated with the frequency of fish consumption. Furthermore,
hair Hg levels in non-fishermen were significantly lower than those in fishermen.
An elevated mean value of (1.44+/-0.79) MUg.g-1(P<0.01), which exceeds the RfD of
1 MUg.g-1, was detected in fishermen. Moreover, hair Hg levels in smokers of
Fuling and Zhongxian County[(0.55+/-0.24) MUg.g-1 and (0.58+/-0.54) MUg.g-1,
respectively] were both markedly higher than those in non-smokers[(0.51+/-0.30)
MUg.g-1 and (0.36+/-0.26) MUg.g-1respectively]. In conclusion, the risk of Hg
exposure to residents of the TGRR was lower. However, in this study, it was
determined that fishermen are at significant risk of Hg exposure.
PMID- 29962171
TI - [Removal of Typical Antibiotics During Aerobic Composting of Human Feces].
AB - Aerobic composting experiments were conducted under three different temperatures
(55C, 35C, and non-temperature-controlled) with human feces and sawdust as the
compost material and bulky matrix respectively. Attention was paid to the effects
of temperature on the removal of four typical antibiotics (tetracycline,
chlortetracycline, sulfadiazine, and ciprofloxacin) during human feces aerobic
composting. Furthermore, three specific experiments were conducted to identify
the possible antibiotic degradation mechanisms in aqueous solution and during
composting with moist sterile sawdust but without feces and composting with feces
and moist sterile sawdust. The most effective removal of the four antibiotics was
achieved through thermophilic composting (55C). At 55C, more than 90% of all the
antibiotics were removed. The degradation of tetracycline and chlortetracycline
was more temperature-dependent than that of sulfadiazine and ciprofloxacin.
Moreover, tetracycline and chlortetracycline removal was primarily through
hydrolysis in moist environments. However, sulfadiazine and ciprofloxacin removal
was mainly attributed to adsorption by sawdust particles. The contribution of
microbial action to antibiotic degradation was insignificant for all the
antibiotics except ciprofloxacin. Up to 20% of this antibiotic was degraded by
microbial action.
PMID- 29962172
TI - [Effect of COD/SO42- Ratio on Anaerobic Digestion of Penicillin Bacterial
Residues].
AB - In order to assess the sulfate-induced inhibition of anaerobic digestion of
antibiotic manufacturing bio-waste. The effect of COD/SO42- ratio on biogas
production potential and substrate utilization characteristics during the
acidogenic phase of anaerobic digestion of penicillin bacterial residues were
investigated through batch experiments. The results obtained indicated that
biogas production was gradually enhanced after 10 days of anaerobic digestion.
However, the maximum cumulative methane production probably exceeded about 208
mL.g-1(on TS basis) since COD/SO42->=3. Because adaptive acclimation, more than
71% COD removal, which may have been converted to methane, was achieved.
Consequently, at COD/SO42-<=1.5, methane production was suppressed by 49% and
100% when the organics and SO42- removal rates were less than 17% and 5%,
respectively. This indicated that methanogens and sulfate-reducing bacteria were
inhibited at high sulfate loading rates. In addition, the COD balance analysis
revealed that less than 9.1% of the COD was converted to methane. However, 5.0%
9.0% of the COD was used for sulfate reduction. This means that methanogens are
more susceptible than sulfate-reducing bacteria to sulfide-induced inhibition.
The S balance showed that the reduced sulfate was mainly present as sulfide in
the digester. A small fraction of it was present as hydrogen sulfide in the
biogas. The analysis of substrate utilization characteristics during the
acidogenic phase revealed that methanation of soluble protein was initiated after
methanation of soluble carbohydrate.
PMID- 29962173
TI - [Characteristics of Odor Emissions from Fresh Compost During Storage and
Application].
AB - The direct application of fresh compost is frequent in practice and might cause
odor pollution. The present study investigated the characteristics of odor
emissions and aimed to estimate the environmental effect of odor over the course
of storage and application. An odors emission potential test lasting 21 days was
conducted using primarily fermented fruit and vegetable waste compost. The
results showed that the fresh compost primarily emitted ammonia, as well as
sulfur compounds, benzenes, and terpenes throughout the experiment. Alcohol and
aldehyde emissions decreased over time, whereas ketone emissions were
consistently low. By simulating two scenarios-one in an enclosed space and one in
open air-the quantity of fresh compost could be applied or stored, and the
protective distance was calculated from the point of odor potential.
PMID- 29962174
TI - [Effects of the Veterinary Antibiotic Sulfamethazine on Ammonia Volatilization
from a Paddy Field Treated with Conventional Synthetic Fertilizer and Manure].
AB - Veterinary antibiotics have been widely detected in croplands due to the
application of animal excrements as fertilizer. However, their effects on ammonia
(NH3) volatilization remain unclear. A field experiment was conducted to evaluate
the effect of sulfamethazine on NH3 volatilization from a paddy field when
conventional synthetic fertilizer or manure was applied as basal fertilizer. Five
different treatments were conducted in this study: without application of
fertilizers and antibiotics (CK), compound fertilizer used as basal fertilizer
with and without the addition of sulfamethazine (CF+SD and CF respectively), and
pig manure used as base fertilizer with and without the addition of
sulfamethazine (CM+SD and CM respectively). Urea was used for topdressing in the
CF, CF+SD, CM, and CM+SD treatments. The results showed that regardless of the
fertilizer type applied, sulfamethazine did not affect the seasonal pattern of
NH3volatilization. However, it promoted the NH3 volatilization rate in the
topdressing stage significantly (P<0.01). During the observation period, the
proportions of applied N lost as NH3-N in the CF+SD and CM+SD treatments were
1.65 and 2.78 times higher than those in the CF and CM treatments, respectively.
The promoting effect of sulfamethazine was more obvious in the pig manure
treatment than in the compound fertilizer treatment. Sulfamethazine significantly
increased the soil urease activity (P<0.05). Furthermore, the NH3 volatilization
rate was positively correlated with urease activity and soil ammonia nitrogen
content (P<0.05). This indicates that sulfamethazine can increase the NH3
volatilization rate by changing the soil urease activity and inorganic nitrogen
content. Controlling the misuse of veterinary antibiotics and environmental and
ecological risks posed by the antibiotic residues in farmland excrements are
urgent problems in China that need to be solved.
PMID- 29962175
TI - A Novel Swimming Performance Test in Rats.
AB - Swimming is an advantageous exercise modality since it induces limited muscle
damage. Performance is a crucial endpoint measurement of physiological relevance
in exercise physiology and clinical settings alike. To our knowledge, the
literature lacks a comprehensive and widely accepted swimming performance
protocol without suffering from high variability in time to exhaustion. Thus, the
present study presents an easily carried out, two-phased swimming performance
incremental test exhibiting low variability in the time to exhaustion among rats.
All nine rats managed to complete the first 12 min-part of the test (phase 1)
with gradually increased loads attached at the base of their tails equal to 2%,
3.5% and 5% (for 4 min each). All rats reached exhaustion at the 10% final load
(phase 2). The mean swimming time until exhaustion, as a measure for defining
exercise performance, was 865 +/- 59 s. In conclusion, we have presented in
detail a novel protocol for practically and satisfactorily measuring swimming
performance in rats characterized by low variability in the time to exhaustion.
This protocol, with the appropriate modifications, can be applied to a wide
spectrum of experimental treatments.
PMID- 29962176
TI - Effect of Lactobacillus Plantarum TWK10 on Improving Endurance Performance in
Humans.
AB - Microbiota is currently an important issue in disease and health and many studies
have revealed it to play an important role in physiological homeostasis and
health promotion. Lactobacillus plantarum (L. plantarum), isolated from Taiwan
pickled vegetables, is a well-known probiotic microorganism. In a recent animal
study, it was shown that supplementation of mice with L. plantarum TWK10 (TWK10)
could increase muscle mass, improve exercise performance and exert anti-fatigue
effects. In order to examine the ergogenic effect of TWK10 supplementation on
endurance performance in humans, we conducted a human double-blind placebo
controlled clinical study. A total of sixteen adult subjects over 20 years of age
were recruited and randomly allocated to the placebo or TWK10 group (n = 8 each).
The TWK10 group received 6 weeks of supplementation. Physiological assessments
were conducted by exhaustive treadmill exercise measurements and related
biochemical indexes. After 6 weeks of supplementation, levels of lactic acid,
blood ammonia, blood glucose, free fatty acid (FFA) and creatine kinase (CK) were
evaluated during exhaustive exercise. We were able to show that the TWK10 group
had significantly higher endurance performance and glucose content in a maximal
treadmill running test compared to the placebo group (P < 0.05), suggesting that
TWK10 supplementation may be beneficial to energy harvest. Taken together, our
results suggest that TWK10 has the potential to be an aerobic exercise supplement
for physiological adaptation or an ergogenic supplement with health benefits for
amateur runners.
PMID- 29962177
TI - Zerumbone from Zingiber zerumbet Ameliorates Lipopolysaccharide-Induced ICAM-1
and Cytokines Expression via p38 MAPK/JNK-IkappaB/NF-kappaB Pathway in Mouse
Model of Acute Lung Injury.
AB - Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality
rates mainly caused by Gram-negative bacteria. Nevertheless, an effective
treatment strategy for ALI is yet to be developed. Zerumbone, a sesquiterpene
isolated from Zingiber zerumbet Smith, possesses several advantageous bioeffects
such as antioxidation, anti-inflammation, and antiulcer. Pretreatment of
zerumbone inhibited lipopolysaccharide (LPS)-induced arterial blood gas exchange,
neutrophils infiltration, and increased pulmonary vascular permeability. LPS
induced expression of intercellular adhesion molecule-1 (ICAM-1) was inhibited by
zerumbone at a lower concentration than that of vascular cell adhesion molecule-1
(VCAM-1). In addition, proinflammatory cytokines, such as interleukin (IL)-1beta
and macrophage inflammatory protein (MIP)-2 were suppressed by zerumbone. The
phosphorylation of nuclear factor (NF)-kappaB, a proinflammatory transcription
factor, and degradation of inhibitor of kappaB (IkappaB), an inhibitor of NF
kappaB, were also reduced by zerumbone. Furthermore, we found the inhibitory
concentration of zerumbone on phosphorylation of p38 mitogen-activated protein
kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was lower than that of
extracellular signal-regulated kinase (ERK). In conclusion, zerumbone could be a
potential protective agent for ALI, possibly via expression of ICAM-1, IL-1beta,
and MIP-2. The protective mechanism of zerumbone was by reversing the activation
of p38 MAPK/JNK-IkappaB/NF-kappaB pathway.
PMID- 29962178
TI - A Single Bout of Exercise Reduces Postprandial Lipemia but Has No Delayed Effect
on Hemorheological Variables.
AB - High plasma triglyceride (TG) concentration in fasting state could cause
hemorheological abnormality, thus increasing the incidence of metabolic diseases.
Exercise has been reported to effectively reduce postprandial TG response. This
study aimed to investigate whether a single bout of pre-prandial exercise can
affect lipemia and hemorheological variables after a high-fat meal. Nine healthy
young male subjects completed two experimental trials. The subjects walked for 1
h at 50% maximal oxygen uptake (VO2max) (the exercise, EX trial), or rested (the
control, CON trial). In the next morning, the subjects consumed a high-fat meal,
and the postprandial lipemia and hemorheological responses were monitored for 6
h. The results showed that postprandial plasma TG concentrations were
significantly lower in the EX trial compared to the CON trial. The postprandial
low-density lipoproteins (LDL) concentration declined in the first 2 h and then
gradually returned to the baseline level in both trials. The postprandial blood
viscosity also decreased in the CON trial. There was no significant difference in
postprandial blood viscosity, red blood cell (RBC) deformation index and
aggregation degree between the trials. There was no significant correlation
between plasma TG concentration and blood viscosity. In conclusion, brisk walking
effectively reduced postprandial TG concentration, but has no significant impact
on postprandial blood viscosity, RBC deformation index and RBC aggregation index.
PMID- 29962180
TI - Effects of Rosuvastatin in combination with Nimodipine in patients with mild
cognitive impairment caused by CSVD.
AB - BACKGROUND: To investigate the clinical efficiency and safeness of the
combination of rosuvastatin and nimodipine in treating mild cognitive impairment
of CSVD patients. METHODS: A total of 120 patients with mild cognitive impairment
caused by CSVD were divided randomly into two groups: an observation group and a
control group, each of which had 60 patients. In the observation group, patients
were given rosuvastatin in combination with nimodipine, and other patients were
given nimodipine in the control group. For the two groups, the course of
treatment was six months. Before and after treatments, levels of TC (total
cholesterol), TG (triacylglycerol), LDL-C (low density lipoprotein-cholesterol),
HDL-C (high density lipoprotein-cholesterol), MMP-9 and hs-CRP (high sensitivity
C reactive protein) were measured. MoCA (Montreal Cognitive Assessment) and ADL
(activities of daily living) were also evaluated. Incidence of adverse reactions
were compared between two groups. RESULTS: The levels of TG, TC and LDL-C were
decreased after treatment in the observation group (P<0.01), and these after
treatment levels were lower than the control group. Additionally, after
treatment, the levels of MMP-9 and hs-CRP were significant lower in the
observation group than the control group. The MoCA and ADL scores were higher in
the observation group than the control group after treatment (P<0.05). Moreover,
the overall effective rate were higher in the observation group (91.7%) than the
control group (65.0%) (P<0.01), while there was no significant difference of the
rate of adverse reactions between the observation group and the control one
(10.0% vs. 8.3%) (P>0.05). CONCLUSIONS: The combination of rosuvastatin and
nimodipine was safe and effective in treating mild cognitive impairment of CSVD
patients.
PMID- 29962179
TI - Low-Intensity Exercise with Blood Flow Restriction Increases Muscle Strength
without Altering hsCRP and Fibrinogen Levels in Healthy Subjects.
AB - Strengthening exercise combined with blood flow restriction potentially increases
muscle strength. This type of exercise does not require heavy weight liftings and
is a feasible method to be performed by persons suffering illnesses. However,
strengthening exercise may induce inflammatory responses due to muscle and
vascular endothelial damage. This study aimed to investigate alterations of high
sensitivity C-reactive protein (hsCRP) and fibrinogen levels in healthy subjects
after five weeks of low intensity resistance training (LIRT) with blood flow
restriction (BFR) on increasing strength in comparison with high intensity
resistance training (HIRT) and LIRT alone, and to evaluate aspects related to the
relative safety of LIRT + BFR. Eighteen healthy subjects were randomized into 3
groups. The HIRT group: 70% of One-Repetition Maximum (1-RM); LIRT + BFR group:
30% of 1-RM with BFR (a modified 13-cm wide cuff was used); LIRT group: 30% of 1
RM. The peak torque of isokinetic contraction of the left elbow flexor in each
subject was measured before and after 5 weeks of resistance exercises to
determine any increases in the left biceps brachii muscle strength. Blood markers
of homeostasis (fibrinogen) and inflammation (hsCRP) were also measured before
and after five weeks of training. Significant increases of strength were
demonstrated between the five weeks of resistance exercises in the HIRT group (P
= 0.003) and the LIRT + BFR group (P = 0.001). Peak torque of isokinetic
contraction of the left flexor elbow joint at 60 degrees per second angular
velocity showed that the LIRT + BFR group produced the greatest peak torque
increase than the HIRT group. There were no significant changes in the hsCRP
levels in all the groups (P > 0.05) after five weeks of intervention. No
significant differences of fibrinogen levels were found in the HIRT group (P =
0.500) and the LIRT + BFR group (P = 0.405), but significant decreases were found
in the fibrinogen levels in the LIRT group (P = 0.017). The LIRT + BFR increases
in the muscle strength were as significant as in HIRT without altering the
fibrinogen and hsCRP levels in the healthy subjects. In this study, LIRT + BFR
showed increase muscle strength without any vascular problems.
PMID- 29962181
TI - Impact of body mass index on female fertility and ART outcomes.
AB - As the global mean body mass index (BMI) is on the rise, the importance of
understanding exactly how female fertility is impacted by once outlier BMI
values, becomes ever more important. Studies have implicated abnormal BMI impacts
the female reproductive system by contributing to anovulation, irregular menses,
adverse oocyte quality, endometrial alterations, and hormonal imbalances that
ultimately result in female infertility, which could complicate natural
conception efforts and request considering assisted reproductive technology (ART)
in such couples. With an increase in the demand for ART, it is crucial to
understand what factors can be altered by the female BMI, in order to maximize
the opportunity for successful pregnancy. The current study aimed to review the
information about the effect of BMI on the female fertility and ART outcomes. The
complex nature of the female reproductive system leaves space for multiple
factors to adversely affect its processes. Imbalances in the hypothalamus
pituitary-ovarian axis can impede efforts for couples to conceive. Leptin and
estrogen are two hormones that have been implicated in regulating BMI as well as
reproductive physiology. Lifestyle modifications prior to, and during ART have
shown promise enhancing fecundity. The intricacies female reproductive system
leaves much to the unknown, and often with conflicting results. Further research
is required to fully elucidate what facets of female fertility are influenced by
BMI, and how the healthcare provider can facilitate successful outcomes. The
current review will enable a better consultation and treatment.
PMID- 29962182
TI - Prevention of pressure ulcers with a motorized air support in at-risk patients
hospitalized in rehabilitation departments APAM + an observational prevalence
study with historical control and incidence study.
AB - BACKGROUND: The main study was a cross-sectional multicenter study of the
prevalence of pressure ulcers in rehabilitation services (RS) where Axtair
Automorpho(r) Plus mattresses were made available ad libitum. The primary
objective was to enable comparison with prevalence as observed in the national
PER SE study (historical control) in similar departments using a variety of
prevention aids. METHODS: This cross-sectional prevalence study was combined with
a prospective study of the incidence of pressure ulcer occurrence in the high
risk target population whose beds were systematically equipped with the studied
support. RESULTS: On the day of the prevalence study, 18 of the 456 patients
presented pressure ulcers which occurred during the period when Axtair
Automorpho(r) Plus supports were made available to the departments. This
corresponds to a prevalence of 3.9% [2.4, 6.2] which is significantly lower than
those recorded in the PER SE study: 11.8% [10.8; 12.8] p <0.0001. The ulcer
incidence study covers 57 patients who were hospitalized on a bed with an Axtair
Automorpho(r) Plus support because of their risk of contracting pressure ulcers.
One pressure ulcer occurred in 3 patients and 3 pressure ulcers occurred in
another patient, i.e. 4 out of 57 corresponding to an incidence of 7.0% [2.0;
17.0]. CONCLUSIONS: The results of the pressure ulcer prevalence study in
rehabilitation departments where Axtair Automorpho(r) Plus supports were
available as well as results of the study of pressure ulcer incidence in patients
bedridden on Axtair Automorpho(r) Plus, confirm the expected benefit provided to
patients in terms of prevention.
PMID- 29962183
TI - Freeze-all strategy in IVF/ICSI cycles: an update on clinical utility.
AB - Over the years concerns have arisen about possible adverse effects associated
with controlled ovarian stimulation (COS) as regards not only the endometrium,
but also on obstetrical and perinatal outcomes in pregnancies after fresh embryo
transfer (ET) during in vitro fertilization (IVF) treatment. The improvements in
cryopreservation techniques associated with the possible impairment in
endometrial receptivity due to the supra-physiologic hormonal levels observed
during conventional COS have increased the implementation of the so-called
'freeze-all' policy. With this strategy, the entire cohort of embryos is
cryopreserved to be transferred to the uterus in subsequent cycles in a more
physiological environment, avoiding the supra-physiologic hormonal levels
observed during COS. The initial studies showed that this strategy could be
beneficial for subgroups of patients, however, the freeze-all policy is being
more and more frequently used for all patient categories. Unfortunately,
currently, no clinical data support this widespread use of the freeze-all
strategy. Based on available trials, it seems justified to implement the strategy
in patients with risk of ovarian hyperstimulation syndrome, hyper-responders and
when performing preimplantation genetic testing for aneuploidy in blastocyst
stage. Therefore, all the other indications, such as implantation failure, high
progesterone levels on the trigger day, advanced maternal age, and endometriosis,
still lack the evidence to support routine use of the freeze-all policy.
PMID- 29962184
TI - Novel insights into the pathophysiology of chemotherapy-induced damage to the
ovary.
AB - Cancer is a worldwide public health problem and is the second leading cause of
death in the United States. Early detection of cancer and advancement of
treatment modalities contributed to declining mortality rates. Consequently,
survival rates increased, leading to a greater interest in maintaining the
quality of life after cancer treatment. Adjuvant chemotherapy results in an
improvement in both disease-free and overall survival. However, chemotherapy
treatment is associated with acute and long- term complications for cancer
survivors. A special concern of women diagnosed with reproductive-age breast
cancer is their reproductive potential after chemotherapy. The chemotherapeutic
agents act by different mechanisms in the ovary. DNA damage of primordial
follicle cells, leading to chemotherapy-induced oocyte apoptosis, was identified
as the main mechanism responsible for the decrease of the ovarian reserve. The
oocyte initially attempts to repair DNA damage through the DNA damage repair
pathway mediated by ataxia-telangiectasia mutated. For cells in which DNA damage
cannot be repaired, elimination occurs via apoptosis. In this review, the
clinical impact and the major mechanisms of chemotherapy-induced ovarian reserve
damage will be briefly described.
PMID- 29962185
TI - The state of the art of preimplantation genetic testing in ART.
AB - Preimplantation genetic testing is a methodology aimed at the assessment of the
genetic composition of an embryo. This diagnostic approach has been used in
assisted reproduction for almost thirty years. During these years, the
technologies used for embryo's genetic analysis have been continuously improved
allowing the development of more precise, comprehensive and robust strategies
that are clinically employed nowadays. In this review, the main diagnostic
approaches used for embryo genetic and chromosomal assessment are described and
discussed both from an embryological and genetic standpoint.
PMID- 29962186
TI - Estimation of age-dependent decrease in blastocyst euploidy by next generation
sequencing: development of a novel prediction model.
AB - BACKGROUND: We developed a model to estimate the female age-dependent decrease in
blastocyst euploidy and the impact of blastocyst cohort size on the likelihood of
having at least one euploid blastocyst for transfer. METHODS: Retrospective
analysis of 1,296 trophectoderm biopsies by next-generation sequencing analysis
from 436 infertile couples undergoing intracytoplasmic sperm injection and
preimplantation genetic testing for aneuploidy. A logistic regression model was
fit to the data. The dependent and independent variables were embryo genetic
status and female age, respectively. The method of fitting was quadratic on age,
and the model was validated with cross validation by a data splitting technique.
RESULTS: The decrease in the probability of blastocyst euploidy follows an age-
dependent binomial distribution, progressing with every year of female age, from
1.2% to 24.5% in 28-44 years-old women (P<0.0001). The minimum number of
blastocysts needed to obtain at least one euploid blastocyst for transfer was
computed for different probabilities and female ages. At the age of 28 years, a
total of three blastocysts is required to obtain at least one euploid blastocyst
with 90% probability, whereas it is 4, 5, 6, 9, 16 and 29 for ages 35, 37, 39,
41, 43, and 45, respectively. CONCLUSIONS: A novel prediction model estimates the
probability of blastocyst euploidy and the number of blastocysts required to
obtain at least one euploid embryo for transfer. This new resource based on
female age and blastocyst cohort size will aid clinicians counsel and plan
treatment of infertile couples undergoing IVF/ICSI.
PMID- 29962187
TI - Methods of surgical sperm extraction and implications for ART success.
AB - Intracytoplasmic sperm injection (ICSI) was developed to overcome the most severe
forms of male factor infertility, including azoospermia. Retrieval of the male
gamete from the epididymis or testis offers the possibility to perform ICSI and
to provide biological parenthood for the affected men. Although reconstruction of
the seminal tract is possible in many men with obstructive azoospermia (OA), this
approach may not be feasible or desired by the couple 1. Unlike OA, non
obstructive azoospermia (NOA) is usually an untreatable condition associated with
spermatogenic failure. In such cases, testicular sperm retrieval and ICSI may be
the only hope for biological fatherhood. In this review, we summarise the recent
evidence about the surgical sperm retrieval (SR) methods for use in association
with ICSI. For the first part, we provide a historical overview of the surgical
sperm retrieval methods development, its indication in both azoospermic and non
azoospermic men, and the technical aspects of each method. For the second part,
we present and critically discuss the evidence concerning the success of ICSI
using non-ejaculated sperm and the consequences of this approach to the health of
resulting offspring.
PMID- 29962188
TI - Mitochondria and reproduction: possibilities for testing and treatment.
AB - Mitochondria, known as the energy factories in all cells, are key regulators of
multiple vital cellular processes and affect all aspects of mammalian
reproduction, being essential for oocyte maturation, fertilization and embryonic
development. Mitochondrial dysfunction is consequently implicated in disease as
well as age-related infertility. Since mitochondria are inherited exclusively
from the mother, the female gamete is central to reproductive outcome and
therapeutic interventions, such as mitochondrial replacement therapies (MRT), and
development of new diagnostic tools. The primary purpose of MRT is to improve
oocyte quality, embryogenesis and fetal development by correcting the imbalance
between mutant and wild-type mitochondrial DNA (mtDNA) in the oocyte or zygote,
either by replacing mutant mtDNA or supplementing with wild-type counterparts
from heterologous or autologous sources. However, the efficacy and safety of
these new technologies have not yet been tested in clinical trials, and various
concerns exist. Nonetheless, the perspectives for such procedures are intriguing
and include two distinct patient populations that could potentially benefit from
the clinical implementation of MRT; (i) patients with mtDNA-disease transmission
risk and (ii) patients undergoing IVF with recurrent poor embryo outcomes due to
advanced maternal age. In this review, we outline the intrinsic roles of
mitochondria during oogenesis and early embryogenesis in relation to disease and
infertility, and discuss the progress in MRT with the developments in
reproductive technologies and the related concerns. In addition, we assess the
use of mtDNA as a potential biomarker for embryo viability in assisted
reproduction.
PMID- 29962189
TI - Best practice in psychological activities in cardiovascular prevention and
rehabilitation: Position Paper.
AB - Recent guidelines on cardiovascular disease prevention suggest multimodal
behavioral interventions for psychosocial risk factors and referral for
psychotherapy in the case of clinically significant symptoms of depression and
anxiety overall. Accordingly, psychologists of the Italian Association for
Cardiovascular Prevention, Rehabilitation and Epidemiology (GICR-IACPR) have
reviewed the key components of psychological activities in cardiovascular
prevention and rehabilitation (CPR). The aim of this study was to elaborate a
position paper on the best practice in routine psychological activities in CPR
based on efficacy, effectiveness and sustainability. The steps followed were: i)
a review of the latest international guidelines and position papers; ii) analysis
of the evidence-based literature; iii) a qualitative analysis of the
psychological services operating in some reference Italian cardiac rehabilitation
facilities; iv) classification of the psychological activities in CPR as low or
high intensity based on the NICE Guidelines on psychological interventions on
anxiety and depression. We confirm the existence of an association between
depression, anxiety, social factors, stress, personality and illness
onset/outcome and coronary heart disease. Evidence for an association between
depression, social factors and disease outcome emerges particularly for chronic
heart failure. Some positive psychological variables (e.g., optimism) are
associated to illness outcome. Evidence is reported on the impact of
psychological activities on 'new' conditions which are now indicated for cardiac
rehabilitation: pulmonary hypertension, grown-up congenital heart, end-stage
heart failure, implantable cardioverter-defribrillator and mechanical ventricular
assist devices, frail and oldest-old patients, and end-of-life care. We also
report evidence related to caregivers. The Panel divided evidence-based
psychological interventions into: i) low intensity (counseling, psycho-education,
self-care, self-management, telemedicine, self-help); or ii) high intensity
(individual, couples and/or family and group psychotherapy, such as stress
management). The results show that psychotherapy is mainly consisting of
cognitive-behavior therapy, interpersonal therapy, and short-term psycho-dynamic
therapy. The current data further refine the working tools available for
psychological activities in CPR, giving clear directions about the choice of
interventions, which should be evidence-based and have at least a minimum
standard. This document provides a comprehensive update on new knowledge and new
paths for psychologists working in the CPR settings.
PMID- 29962190
TI - Ultrasound-guided serratus plane block and image-guided microwave ablation of a
rib metastasis.
PMID- 29962191
TI - Seeking an answer to an unanswered question: gas or drip?
PMID- 29962192
TI - Computerized gait analysis with inertial sensor in the management of idiopathic
normal pressure hydrocephalus.
AB - BACKGROUND: Gait disturbance (GD) is usually the first and most prominent symptom
observed in idiopathic normal pressure hydrocephalus (iNPH). The reversibility of
symptoms is related to early diagnosis and treatment. Nowadays early recognition
of patients is challenging because GD in the elderly is frequently neglected,
leading to late diagnosis and increased disability. In addition, GD is generally
assessed by clinical evaluation since computerized gait analysis methods are
rarely available. In the present study, we demonstrate the clinical application
of an inertial sensor system for gait analysis in iNPH. AIM: The primary aim was
to test the sensor performance in quantifying impairment in gait parameters in
iNPH. The secondary aim was to detect a range of improvement after CSF
subtraction test, which could be considered as predictive of favorable shunt
response. DESIGN: We performed a case-control prospective study from March 2012
to May 2014. SETTING: Inpatients at the Division of Neurology, Department of
Clinical and Experimental Sciences, Brescia. POPULATION: We enrolled 79 patients
with clinical and radiological findings of iNPH and 300 healthy adults over 70
years old without GD as a control group. METHODS: We performed gait analysis, CSF
Tap Test (TT), and shunt surgery in all patients with a diagnosis of iNPH
according to the International Guidelines. According to clinical outcomes, we
divided patients in responsive (group A) and non-responsive (group B). We then
compared pre-operative gait analysis of group A with the control group, and
calculated the percentage of improvement after TT between group A and group B.
RESULTS: Shunt surgery was performed in 52 patients. After 3 months, 35 patients
(group A: 67.3%) showed a positive response to shunt. We quantified the impaired
gait parameters in iNPH and assessed the differences with controls. Improvement
of speed, stride length and double support time after TT was predictive of
positive shunt response. CONCLUSIONS: The proposed inertial sensor system is a
reliable and easy-to-use system for early detection of iNPH and may be used in
any clinical setting. CLINICAL REHABILITATION IMPACT: Identification of a GD
pattern for iNPH, especially in rehabilitation, may be useful for recognizing
patients who are candidates for surgery, thus avoiding permanent disability.
PMID- 29962193
TI - Association of esophageal dilatation in chest CT scan with gastroesophageal
reflux disease: A case control study.
AB - The presence of increased air bubble in the lumina of esophagus on a chest CT
scan may be associated with esophageal disorders. The purpose of this study was
to determine the association between the appearance of air bubbles on chest CT
scan and gastroesophageal Reflux Disease (GERD). In this case-control study,
thirty-two patients with endoscopically proved GERD and 32 subjects without GERD
underwent chest computed tomography (CT) scanning. Esophageal dilatation (ED) was
defined as the presence of air bubbles greater than 10 mm in the supra ventricle
(SV) and ventricle (CV), and air bubbles >15 mm in the ventricle to the lower
esophageal sphincter (V-LES). The results were compared between the two groups.
The GERD patients included 16 (50%) males with a mean age of 58.5+/-11.2 years
and the control group included 17 (54.8%) males and 14 (45.1%) females with a
mean age of 66.7+/-10.5 years. There was a significant relationship between the
presence of GERD and esophageal dilation (ED) in the V-LES sections on the CT
scan (P=0.002). The mean size of the air bubbles in the V-LES section was 11.73
mm in the case group in comparison to 4.32 mm in the control group (P<0.001).
The size and location of the air bubbles in the esophagus can vary and be
important. The possibility of GERD increases in the presence of esophageal
dilation on CT scan.
PMID- 29962194
TI - [The Preparation of Epitope-based Recombinant Rubella Virus Diagnostic Antigen].
AB - To prepare an epitope-based recombinant Rubella virus (RV) recombinant diagnostic
antigen(designated 'H29') and preliminarily evaluate its antigenicity. With
Glutathione S-Transferase (GST) located at the N-terminal, and the His tag at the
C-terminal, the epitope-based RV recombinant diagnostic antigen (designated'H29')
was expressed in Escherichia coli (E.coli) and purified by affinity and anion
exchange chromatography. Based on the antigenicity of H29 identified by Western
blot (WB), we constructed and evaluated a novel early diagnostic ELISA for RV
infection. The soluble H29 protein with a high homogeneity was obtained; the WB
analysis demonstrated that the H29 protein could bind to a monoclonal antibody
for RV-E1 and GST antigens, as well as detect RV acute-phase serum. Using the
novel ELISA, the serum from 48 cases with positive RV infection,48 cases with
negative RV infection, and 48 healthy people was detected, displaying the
excellent consistency. Using prokaryotic expression and chromatography
purification, the epitope-based recombinant RV-IgM diagnostic antigen was
obtained with excellent antigenicity, which could be applied for the serological
detection of the early infection with RV.
PMID- 29962195
TI - [The Expression and Purification of P[4],P[6] and P[8] Rotavirus VP8 * core
Proteins].
AB - P[4], P[6] and P[8] rotaviruses (RVs) are the most prevalent RV genotypes in the
population. In order to further investigate the receptor binding and structural
character of P[4], P[6] and P[8] RVs, VP8 * core proteins of the P[4], P[6] and
P[8] RV strains isolated directly in the stool samples in China were expressed
and purified with the GST and His-tag respectively. The GST-fusion protein was
approximately 46 kDa while the His-tag proteins approximately 20 kDa. In
conclusion, the recombinant plasmids of PGEX4T-1-VP8 * core and pET30a-VP8 * core
were constructed and the VP8 * core proteins were successfully expressed in the
soluble form by using E.coli expression system. These findings provide the basis
for the futhure functional and structural studies of VP8 * proteins.
PMID- 29962196
TI - [Complete Genome Analysis of a Recombinant GI Norovirus Identified in
Huzhou,China].
AB - To study the genotype and genomic and molecular organization of a GI norovirus
isolate from Huzhou, China, the genomic sequence of 2008/Huzhou/N11 was amplified
by RT-PCR, then the PCR product was purified,sequenced, and input into
phylogenetic and Simplot analyses. The complete genomic sequence of the
2008/Huzhou/N11 strain was 7691nucleotides (nt) long. It contained three open
reading frames(ORFs):ORF1,ORF2,and ORF3,with lengths of 5367,1623,and 630 nt,
respectively. Phylogenetic analysis revealed that the RdRp region of
2008/Huzhou/N11 belonged to genotype GI.2,and the VP1 and VP2regions belonged to
genotype GI.6.The SimPlot analysis indicated that potential recombination points
in 2008/Huzhou/N11 were located upstream of the ORF1/ORF2 overlap. The complete
genomic sequence of this recombinant GI.2/GI.6 strain can serve as a reference
sequence for the phylogenetic analysis of norovirus evolution.
PMID- 29962197
TI - [Construction and Immunogenicity Analysis of Herpes Simplex Virus Type 2
Glycoprotein D Recombinant Adenovirus Vaccine].
AB - Herpes simplex virus 2 (HSV-2) is the main pathogen of genital herpes (GH).The
currently available body of evidence suggests that only widespread use of an
effective vaccine can control the spread of HSV-2.We developed a recombinant
replication-defective adenovirus capable of expressing glycoprotein D2(rAd-gD2),
and was identified by PCR and Western blot in gene and protein level,
respectively. The mice in test groups were immunized intramuscularly (i.m.) with
rAd-gD2 in 0and 4 week,while control mice received PBS and AdV. We detected gD2
IgG antibody and neutralizing antibody in order to evaluate of humoral immune
response, detected Th1 (IL-2 and IFN-gamma)/Th2 (IL-4, IL-5 and IL-10) cytokines
in order to evaluate of cellular immune response. The results showed that
immunization with rAd-gD2 could elicit strong gD2IgG(P<0.01)and neutralizing
antibody levels(P<0.05),which were significantly higher than that with PBS and
AdV groups IL-2IFN-gammaIL-4IL-5 and IL-10 detected in rAd-gD2 group were higher
than control groups (P<0.01), Th1/Th2 cytokines were important standard of
cellular/humoral immune response, respectively. The results demonstrated that rAd
gD2 could stimulate not only humoral immune response but also cellular immune
response, rAd-gD2 may be good candidate for the control of HSV-2infection.
PMID- 29962198
TI - [Metagenomic Analysis of Wild Rhesus Monkey Virome in Longhu Mountain in Guangxi
Area, China].
AB - Several viruses have been found in non-human primates, among which some are
pathogenic to humans. To further characterize the spectrum of viruses present in
wild rhesus monkeys, MiSeq high-throughput sequencing were used to analyze 280
fecal samples collected from Guangxi, China. A total of 23,372,679 reads were
obtained, of which 4,641 were annotated to 27 viral families or subfamilies,
including five vertebrate viruses families(78.2%),six insect virus
families(5.5%),eleven plant virus families(10.4%),and other viruses(9.8%).Further
analysis revealed that these reads best fit with the sapelovirus, enterovirus,
parvovirus, adeno-associated virus read sequences shared a high similarity with
the known viruses. However, some reads presented obvious differences from these
viruses. Moreover, PCR amplification was conducted to confirm these potentially
novel viruses. This study had explored the viral spectrum of rhesus monkey feces
in the Guangxi area, which laid the foundation for the potential public health
significance of these viruses.
PMID- 29962199
TI - [Changes in the Expression of AKT and ERK after the JSRV-Env-Induced Transfection
of TC-1 and TC-1-Hyal2 Cells].
AB - This study aims to explore the tumorigenic mechanism of the target cells
following JSRV interaction with its receptor. We transfected mouse lung
epithelial cells (TC-1) and mouse lung epithelial cells stably expressing sheep
Hyal-2(TC-1-Hyal2)with JSRV-Env eukaryotic expression vector, measured the
changes in the mRNA and protein expression of AKT(serine/threonine kinase)and
ERK(extracellular signal-regulated kinase)in cellular signal transduction
pathways, and analyzed the role of sheep Hyal-2in JSRV-Env-induced transformation
of TC-1cells.First,TC-1and TC-1-Hyal2 cells were cultured in vitro and were each
divided into pEGFP-C1-env transfection group,pEGFP-C1 transfection group, and
untransfected group. The expression of key enzymes was determined by PCR and
Western blotting. qPCR showed that, for both cell lines, compared with
untransfected cells, the expression of AKT and ERK1/2mRNA was significantly
increased in the pEGFP-C1-env transfected cells(P<0.05).Western blotting showed
that, relative to untransfected cells, transfection with pEGFP-C1-env
significantly increased p-Akt (S473)protein expression in both cell
lines(P<0.05).Moreover, p-Akt (T308)and p-Erk1/2protein expression was increased
significantly in the pEGFP-C1-env transfected TC-1cells(P<0.05),and very
significantly in the pEGFP-C1-env transfected TC-1-Hyal2cells(P<0.01).Cells of
each type transfected with the empty vector pEGFP-C1 and the untransfected cells
did not show significant differences in their mRNA and protein levels of AKT and
ERK(P >0.05).Thus, the expression of JSRV-Env in the cell lines TC-1and TC-1
Hyal2 activated the cellular signal transduction pathways Ras-Raf-MAPK and PI3K
Akt.The expression of AKT and ERK was significantly increased in pEGFP-C1-env
transfected TC-1and TC-1-Hyal2 cells, but a greater increase was seen in the TC-1
Hyal2 cells.We speculate that Hyal2 plays a catalytic role in JSRV-Env-induced
transformation of TC-1cells.
PMID- 29962200
TI - Sloughing a Precursor Layer to Expose Active Stainless Steel Catalyst for Water
Oxidation.
AB - Hydrogen production by water electrolysis has been regarded as a promising
approach to wean away from sourcing energy through fossil fuels, as the produced
hydrogen gas can be converted to electrical or thermal energy without any harmful
byproducts. However, an efficient hydrogen production is restricted by the
sluggish oxygen evolution reaction (OER) at the counter anode. Therefore, the
development of new OER catalysts with high catalytic activities is crucial for
high performance water splitting. Here, we report a novel sloughing method for
the fabrication of an efficient OER catalyst on a stainless steel (SS) surface. A
chalcogenide (Fe-S) overlayer generated by sulfurization on the SS surface is
found to play a critical role as a precursor layer in the formation of an active
surface during water oxidation. Interestingly, a newly exposed catalytic layer
after sloughing off the Fe-S overlayer has a nanoporous structure with changed
elemental composition, resulting in a significant improvement in OER performance
with an overpotential value of 267 mV at a current density of 10 mA cm-2 (in 1 M
KOH). Our novel method for the preparation of OER catalyst provides an important
insight into designing an efficient and stable electrocatalyst for the water
splitting community.
PMID- 29962201
TI - Nanosized Chiral [Mn6Ln2] Clusters Modeled by Enantiomeric Schiff Base
Derivatives: Synthesis, Crystal Structures, and Magnetic Properties.
AB - Two enantiomeric pairs of new 3d-4f heterometallic clusters have been built from
two enantiomer Schiff base derivatives, labeled as R-/ S-H2L, in situ obtained
from the condensation reactions with o-vanillin and R-/ S-2-phenylglycinol. The
formulas of the series clusters are [Mn6Ln2(MU3-OH)4(MU4-O)(Ac)4(H2O)2( R
L)6].NO3.OH (Ln = Dy (1R), Gd (2R)), [Mn6Ln2(MU3-OH)4(MU4-O)(Ac)4(H2O)2( S
L)6].NO3.OH (Ln = Dy (1S), Gd (2S)), whose crystal structures and magnetic
properties have been characterized. Structural analysis indicated that the above
clusters consisted of a [Mn6Ln2] core, featuring a sandwich configuration. The
results of magnetic measurements showed the presence of slow magnetic relaxation
with the effective energy barrier of 14.85 K in two Dy derivatives under the
condition of zero-dc field, while the significant magnetocaloric effect of Gd
analogues was found in a wide temperature range.
PMID- 29962202
TI - Oxygen Vacancies Mediated Complete Visible Light NO Oxidation via Side-On
Bridging Superoxide Radicals.
AB - It is of a great challenge to seek for semiconductor photocatalysts with
prominent reactivity to remove kinetically inert dilute NO without NO2 emission.
In this study, complete visible light NO oxidation mediated by O2 is achieved
over a defect-engineered BiOCl with selectivity exceeding 99%. Well-designed
oxygen vacancies on the prototypical (001) surface of BiOCl favored the possible
formation of geometric-favorable superoxide radicals (*O2-) in a side-on bridging
mode under ambient condition, which thermodynamically suppressed the terminal end
on *O2- associated NO2 emission in case of higher temperatures, and thus
selectively oxidized NO to nitrate. These findings can help us to understand the
intriguing surface chemistry of photocatalytic NO oxidation and design highly
efficient NO x removal systems.
PMID- 29962203
TI - Getting Drugs into Gram-Negative Bacteria: Rational Rules for Permeation through
General Porins.
AB - Small, hydrophilic molecules, including most important antibiotics in clinical
use, cross the Gram-negative outer membrane through the water-filled channels
provided by porins. We have determined the X-ray crystal structures of the
principal general porins from three species of Enterobacteriaceae, namely
Enterobacter aerogenes, Enterobacter cloacae, and Klebsiella pneumoniae, and
determined their antibiotic permeabilities as well as those of the orthologues
from Escherichia coli. Starting from the structure of the porins and molecules,
we propose a physical mechanism underlying transport and condense it in a
computationally efficient scoring function. The scoring function shows good
agreement with in vitro penetration data and will enable the screening of virtual
databases to identify molecules with optimal permeability through porins and help
to guide the optimization of antibiotics with poor permeation.
PMID- 29962204
TI - One-Pot Access to peri-Condensed Heterocycles via Manganese-Catalyzed Cascade C-N
and C-C Bond Formation.
AB - A Mn(III)-catalyzed three-component cascade C-H/N-H functionalization of 2
aminopyridines with 2 equiv of dialkyl butyndioates leads to peri-condensed
tricylic azines through a selective, but partly destructive, stoichiometry. A
wide range of 2,11-diazatricyclo[5.3.1.04,11]undeca-1(10),4,6,8-tetraen-3-ones
were thus obtained with moderate to high yields in a step-economical fashion
under mild conditions. This transformation can serve as a concise method for
constructing valuable precursors of functional materials and biologically active
compounds.
PMID- 29962205
TI - Discovery of 4-Hydroxy-3-(3-(phenylureido)benzenesulfonamides as SLC-0111
Analogues for the Treatment of Hypoxic Tumors Overexpressing Carbonic Anhydrase
IX.
AB - Herein we report the 2-aminophenol-4-sulfonamide 1 and its ureido derivatives 2
23 as inhibitors of the carbonic anhydrase (CA, EC 4.2.1.1) enzymes as analogues
of the hypoxic tumor phase II entering drug SLC-0111. This scaffold may determine
preferential rotational isomers to selectively interact within the tumor
associated CAs. Most of the compounds indeed showed in vitro selective inhibition
of the tumor associated CA isoforms IX and XII. The most potent derivative within
the series was 11 ( KIs of 2.59 and 7.64 nM on hCA IX and XII, respectively),
which shares the 4-fluorophenylureido tail with the clinical candidate. We
investigated by means of X-ray crystallographic studies the binding modes of
three selected compounds of this series to CA I. The evaluation of therapeutic
efficacy of compound 11 in an orthotopic, syngeneic model of CA IX-positive
breast cancer in vivo showed close matching antitumoral effects and tolerance
with SLC-0111.
PMID- 29962206
TI - Late-Season Shiraz Berry Dehydration That Alters Composition and Sensory Traits
of Wine.
AB - Late-season berry dehydration (LSD) is a common occurrence in Shiraz grapes,
particularly those grown in hot climates. LSD results in significant yield
reductions; however, the effects on wine composition and sensory characteristics
are not well-documented. Wines made of 100% nonshriveled clusters (control) were
related to red fruit flavors by the sensory panel, whereas wines made of 80%
shriveled clusters (S-VCT) were perceived as more alcoholic and associated with
dark fruit and dead/stewed fruit characters. The latter wines also resulted in
higher concentrations of massoia lactone and gamma-nonalactone, compounds known
to contribute to prune and stewed-fruit aromas. Wines made of shriveled grapes
were also characterized by an increase in C6-alcohols and a decrease in esters,
whereas wine terpenoids were altered compound-specific. An increase in orange
pigments and wine chemical age in S-VCT wines indicated faster oxidative aging
compared to the control. LSD appeared to alter final wine composition directly
but also appeared to influence yeast metabolism, potentially due to an alteration
of the composition of lipids in the grape juice. This study emphasized the
relevance of sorting shriveled and nonshriveled berries for final wine chemical
composition and wine style.
PMID- 29962207
TI - Saliva and Flavor Perception: Perspectives.
AB - This paper reports the main trends and perspectives related to the current
understanding of the relationships between saliva and flavor perception. Saliva
is a key factor in flavor perception and controls the transport of flavor
molecules to their receptors, their adsorption onto the mouth surfaces (i.e.,
oral mucosa), their metabolism by enzymatic modification, and the friction force
in the oral cavity. The proteins in free saliva or in the mucosal pellicle
contribute to flavor perception by interacting with or metabolizing flavor
compounds. Most of these reactions were observed when using fresh whole saliva;
however, they were absent or less frequently observed when using artificial
saliva or depleted/frozen whole saliva. There is a need to better understand the
role of protein aggregates in flavor perception. Within humans, there is great
interindividual variation in salivary composition, which has been related to
differences in flavor perception. However, the relative role of salivary proteins
and the microbiota should be deeply investigated together with the impact of
their composition on individual perception during life. Finally, future results
must also consider cross-modal interactions at the brain level.
PMID- 29962208
TI - "Doping" of Polyyne with an Organometallic Fragment Leads to Highly Conductive
Metallapolyyne Molecular Wire.
AB - Exploration of highly conductive molecules is essential to achieve single
molecule electronic devices. The present paper describes the results on single
molecule conductance study of polyyne wires doped with the organometallic
Ru(dppe)2 fragment, X-(C=C) n-Ru(dppe)2-(C=C) n-X. The metallapolyyne wires end
capped with the gold fragments (X = AuL) are subjected to single-molecule
conductance measurements with the STM break junction technique, which reveal the
high conductance (10-3-10-2 G0; n = 2-4) with the low attenuation factor (0.25 A
1) and the low contact resistance (33 kOmega). A unique "'doping'" effect of
Ru(dppe)2 fragment was found to lead to the high performance as suggested by the
hybrid density functional theory-nonequilibrium green function calculation.
PMID- 29962209
TI - Primary Care Providers' Awareness of Physical Activity-Related Intensive
Behavioral Counseling Services for Cardiovascular Disease Prevention.
AB - PURPOSE: The US Preventive Services Task Force recommends that adults at risk for
cardiovascular disease (CVD) be offered or referred to intensive behavioral
counseling interventions to promote a healthful diet and physical activity for
CVD prevention. We assessed primary care providers' (PCPs) awareness of local
physical activity-related behavioral counseling services, whether this awareness
was associated with referring eligible patients, and the types and locations of
services to which they referred. DESIGN: Cross-sectional survey. SETTING: Primary
care providers practicing in the United States. SUBJECTS: 1256 respondents.
MEASURES: DocStyles 2016 survey assessing PCPs' awareness of and referral to
physical activity-related behavioral counseling services. ANALYSIS: Calculated
prevalence and adjusted odds ratios (aORs). RESULTS: Overall, 49.9% of PCPs were
aware of local services. Only 12.6% referred many or most of their at-risk
patients and referral was associated with awareness of local services (aOR =
2.81, [95% confidence interval: 1.85-4.25]). Among those referring patients,
services ranged from a health-care worker within their practice or group (25.4%)
to an organized program in a medical facility (41.2%). Primary care providers
most often referred to services located outside their practice or group (58.1%).
CONCLUSION: About half of PCPs were aware of local behavioral counseling
services, and referral was associated with awareness. Establishing local
resources and improving PCPs' awareness of them, especially using community
clinical linkages, may help promote physical activity among adults at risk for
CVD.
PMID- 29962210
TI - Fall prevention programs for culturally and linguistically diverse groups:
program provider perspectives.
AB - OBJECTIVES: Older people from culturally and linguistically diverse (CALD)
backgrounds are one of the fastest growing and rapidly ageing population segments
in Australia. This qualitative study aims to explore the experiences, needs and
challenges that individual program providers encountered in implementing and
delivering a fall prevention program for CALD groups and meeting the linguistic,
cultural and contextual needs of the program participants. DESIGN: Semi
structured in-depth interviews were conducted with a convenience sample of 24
program providers implementing, delivering or supporting fall prevention programs
including Stepping On for CALD groups. Interview transcripts were analysed using
thematic analysis. RESULTS: Two major themes emerged: (1) extra layers of
complexity are needed in program planning, delivery, recruitment and enabling
participation of older people from CALD background and (2) program leaders 'going
the extra mile' influences success of the program. Complexity included
accommodating the linguistic and sociocultural needs in planning the programs,
knowing and using the 'right way' to reach and deliver the program to CALD groups
and understanding the nuances of facilitating program participation. While it was
important to ensure the acceptability and accessibility of the program for the
older people from diverse CALD communities, it was the drive and determination of
the program leader and their striving for cultural relevance that made the
program possible. Sustainability and wider implementation requires unique support
and additional resources. CONCLUSION: These findings can be used by program
providers, policy-makers and health researchers to improve the capacity of fall
prevention programs to better respond to the growing diversity in needs and
preferences among older populations in Australia and internationally.
PMID- 29962212
TI - Empagliflozin-Induced Pancreatitis.
PMID- 29962211
TI - DNA Methylation of Proximal PLAT Promoter in Chronic Rhinosinusitis With Nasal
Polyps.
AB - Background Nasal polyps (NP) are characterized by pseudocysts derived from
stromal tissue edema and cause persistent infections in patients with chronic
rhinosinusitis (CRS). A low level of tissue-type plasminogen activator (gene name
PLAT) is considered a cause of stromal tissue edema because of insufficient
plasmin activation in NP; however, the mechanism regulating PLAT gene expression
levels is still unclear. The epigenetic mechanism regulating the PLAT gene
expression has been studied in other tissues. Objective We aimed to investigate
the methylation levels in the proximal PLAT promoter and their effects on gene
expression in NP tissue. Methods We investigated the methylation levels at 3 CpG
sites in the proximal PLAT promoter regions (-618, -121, and -105 with respect to
the transcription initiation site) by bisulfite pyrosequencing and their effects
on the gene expression by quantitative real-time polymerase chain reaction (qPCR)
in 20 paired samples of NP and inferior turbinate tissue (IT) from patients with
CRS. Results The DNA methylation levels at all CpG sites were higher ( P < .01),
and the PLAT expression was lower ( P < .001) in NP compared with IT. The
methylation changes at the -618 site showed a negative correlation with the gene
expression changes between NP and IT ( r = -.65, P < .01). Conclusions
Hypermethylation of PLAT promoter may downregulate the gene expression in NP,
leading to excessive fibrin deposition by aberrant coagulation cascade. DNA
methylation of proximal PLAT promoter may contribute to NP growth and have a
potential as a new therapeutic target.
PMID- 29962213
TI - Ozenoxacin: A Novel Topical Quinolone for Impetigo.
AB - OBJECTIVE: To review the data supporting Food and Drug Administration (FDA)
labeling of ozenoxacin and evaluate its place in therapy for impetigo. DATA
SOURCES: A literature search was conducted using PubMed (1966 to May 2018) and
Google Scholar (2000 to May 2018) with the search terms ozenoxacin, T-3912, and
GF-001001-00. Other resources included clinicaltrials.gov , the manufacturing
product label, and the FDA website. STUDY SELECTION AND DATA EXTRACTION: All
relevant English-language data from abstracts, phase 1 to 4 studies, and review
articles were included. DATA SYNTHESIS: FDA labeling of ozenoxacin was based on 2
phase 3 studies conducted in patients 2 months of age and older. Ozenoxacin
demonstrated efficacy and safety for use in bullous or nonbullous impetigo from
Staphylococcus aureus or Streptococcus pyogenes as compared with placebo. The
lack of systemic absorption results in minimal adverse drug reactions. Studies
did not detect possible adverse events commonly associated with other quinolone
antibiotics. Relevance to Patient Care and Clinical Practice: This topical
quinolone has bactericidal activity against Gram-positive organisms, including
methicillin-resistant Staphylococcus aureus. Ozenoxacin may have an expanded
clinical role for the treatment of localized impetigo if resistance to current
therapies increases significantly. However, ozenoxacin is unlikely to play a
significant role in the treatment of impetigo in the foreseeable future, because
of lack of direct comparative clinical efficacy data with currently recommended
therapies and likely high cost. CONCLUSIONS: Ozenoxacin, the first nonfluorinated
quinolone, is a safe, topical treatment for impetigo in patients 2 months of age
and older. Although clinical trials demonstrate efficacy compared with placebo,
comparative trials to current treatment options are needed to identify its
therapeutic use.
PMID- 29962214
TI - Voice Abnormalities and Laryngeal Pathology in Preterm Children.
AB - INTRODUCTION: The prevalence of voice abnormalities in children born prematurely
has been reported to be as high as 58%. Few studies have examined these
abnormalities with laryngoscopic or videostroboscopic findings and characterized
their laryngeal pathologies. OBJECTIVE: To review voice abnormalities in patients
with a history of prematurity and characterize the etiology of their voice
problems. A secondary objective is to see if there is a correlation between the
findings and the patient's intubation and surgical history. METHODS: A
retrospective chart review was conducted of all preterm patients seen in voice
clinic at a tertiary pediatric hospital. Demographic data, diagnoses, and office
laryngoscopies were reviewed as well as any speech therapy evaluations and/or
medical and surgical treatments. RESULTS: Fifty-seven patients were included.
Mean age at presentation was 5.1 (+/-4.3) years. Mean gestational age was 27.8
(+/-3.7) weeks. Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)
perceptual evaluations included a mean overall dysphonia severity of 46.6 (+/
24.2). Patients who had undergone prolonged intubation (?28 days) in the NICU or
had prolonged NICU stays (>12 weeks) had significantly higher overall dysphonia
severity scores. Thirty-three patients with vocal fold hypo- or immobility had
significantly greater voice deviance in breathiness, loudness, and overall
severity compared to those without vocal fold immobility. Of all patients, 35%
were recommended surgical intervention and 49% voice therapy. CONCLUSION:
Intubation greater than 28 days and prolonged NICU stays are associated with more
severe dysphonia in premature patients. There should be a low threshold for
clinical evaluation of dysphonia in this unique patient population.
PMID- 29962215
TI - Responding to adverse childhood experiences: A paediatrician's perspective.
PMID- 29962216
TI - Antioxidant intake in relation to serum C-reactive protein in mid-life and older
African Americans.
AB - OBJECTIVE: African Americans (AAs) experience greater prevalence of
cardiovascular disease (CVD) compared to other ethnic/racial groups. Low-grade
chronic inflammation (often quantified by serum C-reactive protein CRP) is a well
documented risk factor for CVD. A healthy diet is plentiful in antioxidant
nutrients and is associated with a lower inflammatory status and CVD risk. Our
objective was to examine the relationship between dietary intake of antioxidants
(carotenoids, vitamins A, C, E, and selenium) and serum CRP concentrations in mid
life and older AAs, while controlling for confounders. METHODS: Data were from
the baseline phase of a longitudinal church-based intervention study to reduce
CVD risk in AAs. Anthropometrics were measured in a standard manner. Fasting
serum samples were analyzed with ELISA for CRP. Multiple-pass 24-hour dietary
recalls were used to assess intake; self-reported questionnaires were used to
collect demographics. Statistical analyses were performed using SPSS Statistics
21 with the level of significance set at p < 0.05. RESULTS: A total of n = 73
participants (n = 51 females) were included in the analyses. The females and
males, respectively were 58.9 +/- 10.3 and 59.4 +/- 9.7 years old, with BMI of
34.6 +/- 8.3 and 35.6 +/- 9.3 kg/m2 (Mean +/- SD). The mean serum CRP was above
0.6 mg/dL, although slightly lower in males. Males consumed more energy (kcal)
and met RDA for selenium, whereas females met RDA for vitamin C. Both groups met
RDA for vitamin A. All other dietary variables fell below the RDA or had no RDA
established. Results from the binary logistic regression did not show significant
association between dietary antioxidants and serum CRP in males or females.
However, among females, for every unit increase in BMI, there was a 15% increase
in serum CRP (OR = 1.15, p = 0.04). CONCLUSIONS: Our study does not support the
inverse relationship between antioxidants intake and CRP, but does support the
evidence for obesity-induced inflammation and suggests the association can be
applied to AA women.
PMID- 29962217
TI - What's in a name?
PMID- 29962218
TI - Surrogate non-motherhood: Israeli and US surrogates speak about kinship and
parenthood.
AB - Drawing on a comparison of two ethnographic research projects on surrogacy in the
United States and Israel, this paper explores surrogates' views about motherhood
and parenthood, relationships and relatedness. The paper challenges three myths
of surrogacy: that surrogates bond with the babies they carry for intended
parents, that it is immoral not to acknowledge the surrogates' maternity, and
that surrogacy upsets the moral order of society by dehumanizing and commodifying
reproduction. Contrasting the similarities and differences in the voices of
surrogates from these studies, the authors argue that surrogates draw on ideas
about technology, genetics and intent in order to explain that they do not bond
with the child because they are not its mother. This is followed by an
exploration of surrogates' definitions of what constitutes parenthood, suggesting
that in both contexts, surrogates draw clear boundaries between their own family
and that of the intended parents. Finally, it is suggested that surrogates expect
a relationship, or a bond, to develop with the intended parents and view their
contribution as exceptional moral work which involves nurturing, caring,
friendship and solidarity. The paper concludes that for surrogates in the USA and
in Israel, maternity, bonding and kin-ties are not automatic outcomes of
pregnancy, but a choice. Surrogates in both contexts hold that bonding with other
people's children as if they were one's own is wrong while bonding with their
couple and creating 'fictive kin' ties with them is the logical outcome of the
intense and intimate process of collaborative baby-making.
PMID- 29962219
TI - Idiopathic Growing Pains in Pediatric Patients: Review of Literature.
PMID- 29962220
TI - Exploring the Quality of Anticoagulant Prescribed for Patients With Atrial
Fibrillation at the St John of God Hawkesbury District Health Centre, New South
Wales, Australia.
AB - BACKGROUND: Limited data are available on the clinical management of atrial
fibrillation (AF) and its outcomes from an Australian perspective. OBJECTIVE: To
describe the appropriateness of antithrombotic prescribing for patients who
presented with a diagnosis of AF to the Hawkesbury St John of God Hospital, New
South Wales, Australia. METHODS: This retrospective observational study reviewed
patients admitted to St John of God Hawkesbury Hospital with AF between June 2016
and June 2017. We calculated stroke risk using the CHA2DS2-VASc score based on
medical records and reviewed the appropriateness of oral anticoagulant (OAC)
prescribing compared to the 2016 European Society of Cardiology guidelines.
Patients were excluded if they had only 1 episode of AF that reverted either
spontaneously or upon cardioversion without any documented recurrences. RESULTS:
A total of 200 patients (18 years) were included, with 180 (90%) deemed eligible
for anticoagulation. Of these 72.8% (n = 131) were prescribed an OAC. A total of
40.0% of patients at low risk of stroke and 68.4% at intermediate risk were
prescribed an OAC, respectively. Apixaban was the direct OAC of choice with 36.6%
of patients prescribed an OAC receiving apixaban. Warfarin was prescribed for
25.1% of the patients who were prescribed an OAC. CONCLUSIONS: The
underutilization of anticoagulant medication in high-risk groups and over
utilization in low-risk groups remains an ongoing issue in contemporary AF
management, and it highlights the need to improve AF-related stroke prevention in
our jurisdiction.
PMID- 29962221
TI - The combined effect of ambient ozone exposure and toxic air releases on
hospitalization for asthma among children in Harris County, Texas.
AB - This study represents an analysis of the effect of exposure to ambient ozone and
toxic air releases on hospitalization for asthma among children in Harris County,
Texas. Our study identified temporal and spatial variations in asthma
hospitalization across the study region and explored the combined effect of
exposure to ambient ozone and air toxics on asthma hospitalization. Asthma
hospitalization hot spots and clusters were mostly not located on zip codes with
reported high quantities of total air releases of chemical pollutants. There was
no significant interaction between ambient ozone exposure and toxic air releases
relative to asthma hospitalization. The major predictor of asthma hospitalization
was season, with hospitalization rate per 10,000 people for asthma being highest
in winter period when ozone levels are usually lowest.
PMID- 29962222
TI - Texting: Implications for health and social connectedness.
PMID- 29962223
TI - Interactions between race/ethnicity, poverty status, and pregnancy cardio
metabolic diseases in prediction of postpartum cardio-metabolic health.
AB - BACKGROUND: Prenatal health disparities exist for African Americans and low
socioeconomic status (SES) individuals when compared to non-Hispanic Whites and
people of higher SES, particularly in cardio-metabolic diseases. Furthermore,
having had a pregnancy-specific cardio-metabolic disease, e.g. preeclampsia,
increases risk for future cardio-metabolic disease. Although these factors (race,
SES and pregnancy cardio-metabolic disease) are interrelated, studies have rarely
considered their combined effect on postpartum cardio-metabolic risk. The purpose
of this study was to assess whether SES, race/ethnicity, and prenatal cardio
metabolic disease interact in the prediction of postpartum cardio-metabolic risk.
METHODS: A sample of 1,753 low-income women of African American, Latina, non
Hispanic White race/ethnicity was recruited after a birth in 5 US sites.
Household income was used to categorize poverty status as Poor (< Federal Poverty
Level; FPL), near poor (100-200% FPL), or low/middle income (> 200% FPL). Three
prenatal cardio-metabolic disease diagnoses (preeclampsia, gestational
hypertension, gestational diabetes) were identified from medical records. Four
biomarkers (mean arterial pressure, glycosylated haemoglobin, total
cholesterol:HDL ratio, and waist-hip ratio) were collected at 6 and 12 months
postpartum, and combined into an average postpartum cardio-metabolic risk index.
Maternal age, pre-pregnancy body mass index, parity, health behaviors and
employment status were covariates. RESULTS: Analyses revealed interactions of
race/ethnicity, poverty status, and prenatal cardio-metabolic diseases in the
prediction of postpartum cardio-metabolic risk. African American women had higher
postpartum cardio-metabolic risk, which was exacerbated following a prenatal
cardio-metabolic disease. Low/middle income African American women had higher
cardio-metabolic risk compared to poor African American, and all Latina and White
women. CONCLUSIONS: African American women, and especially those who experienced
pregnancy complications, emerged as vulnerable, and greater household income did
not appear to confer protection against worse postpartum cardio-metabolic risk
for this group. These results highlight the complex interplay between
socioeconomic status and race/ethnicity with respect to understanding health
disparities.
PMID- 29962224
TI - Health-Related Internet Use Among Otolaryngology Patients.
AB - OBJECTIVE: The association between online health resources use in specific
otolaryngology patients is poorly understood. To better understand health-related
Internet use by otolaryngology patients, we surveyed first-visit patients at
academic and private practice clinics in Iowa. METHODS: Data on socioeconomic
status, access, and utilization of online resources were collected. Age
distributions were compared by t test, and categorical variables were compared by
chi-square analysis. Multivariate logistic regression was used to estimate odds
ratios for association between independent variables (age, sex, educational
attainment, otolaryngology subspecialty, etc). RESULTS: Data showed that 8.7%
lacked Internet access; an additional 5.4% reported access only in a public place
or at work. Younger, more educated, and more urban patients reported higher rates
of Internet access. Among university patients, patients seeing head and neck
oncologists were most likely to report no Internet access (10.9%). Just over one
third of patients used the Internet to research their health condition prior to
their appointment. CONCLUSIONS: Internet access was far from universal among this
large cohort of otolaryngology outpatients. Head and neck cancer (HNC) patients
report the least online access among all otolaryngology subspecialties. Providers
should consider nonelectronic patient resources for older, more rural, less
educated, and HNC patient populations as online/electronic methods of
communication may not be accessible to these groups.
PMID- 29962225
TI - Genetic variation at the long noncoding RNA H19 gene is associated with the risk
of hypertrophic cardiomyopathy.
AB - AIM: The long noncoding RNA H19 and its host micro RNA miR-675 have been found
deregulated in cardiac hypertrophy and heart failure tissues. Our aim was to
investigate whether the H19 gene variants were associated with the risk of
hypertrophic cardiomyopathy (HCM). PATIENTS & METHODS: We genotyped two H19 tag
single nucleotide polymorphisms in 405 HCM patients and 550 controls, and
sequenced this gene in 100 patients. RESULTS: The rs2107425 C was significantly
increased in sarcomere no-mutation patients (n = 225; p = 0.01): CC versus CT +
TT, p = 0.017; odd ratios: 1.51. Sequencing of the H19 coding transcript
identified two patients heterozygous carriers for a rare variant, rs945977096
G/A, that was absent among the controls. CONCLUSION: Our study suggested a
significant association between H19 variants and the risk of developing HCM.
PMID- 29962226
TI - Physical activity behaviours of persons living with HIV of low socioeconomic
status: domain, intensity and sociodemographic correlates.
AB - Physical activity (PA) is healthy for People Living with HIV and AIDS (PLWHA).
This study examined the PA profile of 978 PLWHA based on PA domains and PA
intensity. The study also sought to determine whether employment status and level
of education can predict PA among PLWHA of low SES. PA and sociodemographic data
of 978 PLWHA of mean age 35 (8.77) years were collected using the global physical
activity questionnaire and a sociodemographic questionnaire. Results showed that,
participants engaged more in work-related PA [160.11 (346.95) min/wk], followed
by transport related PA [115.21(SD = 142.04) min/wk], and lastly in leisure
related PA [40.84 (SD = 110.37) min/wk]. Participants also engaged more in
moderate PA [265.86 (SD = 335.45) min/wk], than in vigorous PA [50.29 (SD =
205.30) min/wk]. Employment was a significant predictor of overall PA controlling
for age, CD4 count and education level. The model explained 2.5% of the variance
(R2 = 0.025) on overall PA and tested significant at a 0.01 alpha level (p <
0.01). PA interventions for this population should be domain- and intensity
specific. Researchers promoting healthy lifestyle behaviour change can benefit
from determining the factors that facilitate domain-specific PA.
PMID- 29962227
TI - Long-term effects of highly challenging balance training in Parkinson's disease-a
randomized controlled trial.
AB - OBJECTIVES:: To determine long-term effects of a highly challenging training
program in people with Parkinson's disease, as well as describe how initially
observed improvements of the program deteriorated over time. DESIGN:: Long-term
follow-up of previously reported outcomes at 10 weeks of a randomized controlled
trial. SETTING:: University hospital setting. PARTICIPANTS:: One-hundred elderly
with mild-to-moderate (Hoehn and Yahr 2-3) Parkinson's disease. INTERVENTIONS::
Participants in the training group ( n = 51) received 10 weeks (three times/week)
of balance and gait exercises, incorporating dual-tasks, while the control group
( n = 49) received care as usual. MAIN OUTCOME MEASURES:: Balance control (Mini
Balance Evaluation System Test (Mini-BESTest)) and gait velocity. Mixed-design
analyses of variance were used to determine potential training effects at 6- and
12-month follow-up, and piecewise regression models predicted the rate of
deterioration. RESULTS:: Seventy-six participants were included at final follow
up. No significant ( P > .05) between-group differences remained at either 6 or
12 months following the intervention. The mean Mini-BESTest scores of the
training and control group were 19.9 (SD 4.4) and 18.6 (SD 4.3), respectively, at
the 12-month follow-up. Gait speed was 1.2 (SD 0.2) m/s in both groups at 12
months. The training group showed a larger deterioration rate per month in
balance performance (0.21 point) and gait velocity (0.65 cm/s) than controls ( P
< .05). CONCLUSION:: These results suggest that training effects diminish within
6 months after balance training, implying that the program may need to be
repeated regularly.
PMID- 29962228
TI - American Indian women cancer survivors' perceptions and experiences with
conventional and non-conventional mental health care for depressive symptoms.
AB - BACKGROUND: Despite cancer and depression being disproportionately high for
American Indian and Alaska Native (AI/AN) women, such cancer survivors' help
seeking practices and perceptions related to depression are absent in extant
research. A broader context of historical oppression has set the stage for
unequal health outcomes and access to quality services. The purpose of this
article was to explore AI women cancer survivors' experiences with conventional
mental health services and informal and tribally-based assistance, as well as
barriers related to mental health service utilization. METHODS: A qualitative
descriptive study methodology, with qualitative content analysis, was used to
examine the experiences of AI women cancer survivors as they related to help
seeking experiences for depressive symptoms. The sample included 43 AI women
cancer survivors (n = 14 breast cancer, n = 14 cervical cancer, and n = 15 colon
and other types of cancer survivors). RESULTS: Since receiving a cancer
diagnosis, 26 (62%) participants indicated they had feelings of depression. Some
participants (n = 13) described mixed perceptions of the mental health service
system. Generally, participants viewed families and informal support systems as
primary forms of assistance, whereas conventional services were reported as a
supplementary or 'as needed' forms of support, particularly when the informal
support system was lacking. Participants received help in the forms of
psychotropic medications and psychotherapy, as well as help from family and AI
specific healing modalities (e.g. sweat lodges and healing ceremonies). Stigma
and confidentiality concerns were primary barriers to utilizing conventional
services as described by 12 (29%) participants. DISCUSSION: Participants' help
primarily came from family and tribally-based entities, with conventional mental
health care being more salient when informal supports were lacking. The mixed
perceptions espoused by participants may be related to a broader context of
historical oppression; family and social support and tribally-based services may
be protective factors for cancer survivors with depression.
PMID- 29962229
TI - Human-biomonitoring and individual soil measurements for children and mothers in
an area with recently detected mercury-contaminations and public health concerns:
a cross-sectional study.
AB - In this study, we assessed intracorporal mercury concentrations in subjects
living on partially mercury-contaminated soils in a defined area in Switzerland.
We assessed 64 mothers and 107 children who resided in a defined area for at
least 3 months. Mercury in biological samples (urine and hair) was measured, a
detailed questionnaire was administered for each individual, and individual
mercury soil values were obtained. Human biomonitoring results were compared with
health-related and reference values. Mothers and children in our study had
geometric means (GMs) of 0.22 ug Hg/g creatinine in urine (95th percentile (P95)
= 0.85 ug Hg/g) and 0.16 ug Hg/g (P95 = 0.56 ug Hg/g), respectively. In hair,
mothers and children had GMs of 0.21 ug Hg/g (P95 = 0.94 ug/g) and 0.18 ug/g (P95
= 0.60 ug/g), respectively. We found no evidence for an association between
mercury values in soil and those in human specimens nor for a health threat in
residential mothers and children.
PMID- 29962230
TI - Comparing disability between traumatic brain injury and spinal cord injury using
the 12-item WHODAS 2.0 and the WHO minimal generic data set covering functioning
and health.
AB - OBJECTIVE:: To compare disability between two patient groups using short
validated tools based on International Classification of Functioning, Disability
and Health (ICF). DESIGN:: Cross-sectional study. SETTING:: University hospital
specialist outpatient clinic. SUBJECTS:: A total of 94 patients with traumatic
brain injury and 59 with spinal cord injury. MAIN MEASURES:: Disability evaluated
using self-reported and proxy 12-item WHODAS 2.0 (World Health Organization
Disability Assessment Schedule), and physician-rated WHO minimal generic data set
covering functioning and health. RESULTS:: The two measures used showed severe
but very different disabilities in these patient groups. Disability was assessed
worse by physicians in the spinal cord injury population (sum 15.8 vs. 12.7, P =
0.0001), whereas disability assessed by the patients did not differ significantly
between the two groups (sum 18.4 vs. 21.2). Further analysis revealed that in
patients with "high disability" (the minimal generic data set score ?15), self
reported functioning was more severely impaired in the traumatic brain injury
group compared to the spinal cord injury group (29.7 vs. 21.4, P < 0.0001), with
no difference between these two diagnostic groups in patients with "low
disability" (the minimal generic data set below 15). Patients with traumatic
brain injury perceived more difficulties in cognition, getting along and
participation, patients with spinal cord injury in mobility and self-care.
CONCLUSION:: Both generic measures were able to detect severe disability but also
to detect differences between two patient populations with different underlying
diagnoses.
PMID- 29962231
TI - A new diphenolic metabolite isolated from the marine-derived fungus Aspergillus
niger 102.
AB - A new diphenolic derivative asperdiphenol A (1), along with nine known compounds
(2-10), was isolated from the marine-derived fungus Aspergillus niger 102. Their
structures were elucidated on the basis of spectroscopic analysis including NMR
and MS spectrometry. Compound 1 was suggested to be a chiral mixture by the
specific rotation and chiral HPLC. Compound 1 was evaluated for its anti
inflammatory, antibacterial, and cytotoxic activity.
PMID- 29962232
TI - Endobronchial Non-Tuberculosis Mycobacterium Infection Presenting in a Healthy
Child.
AB - OBJECTIVES: To describe a safe and effective treatment for endobronchial
Mycobacterium avium complex. METHODS: Case report and literature review. RESULTS:
We present a case of endobronchial M. avium complex in a healthy child treated
with serial carbon-dioxide laser excisions and antibiotic triple therapy using
azithromycin, rifampin, and ethambutol. No current guideline for the treatment of
these lesions in the pediatric population exists. CONCLUSIONS: In patients with
airway impingement, serial endoscopic surgical resection combined with
antibiotics can provide safe and effective management.
PMID- 29962233
TI - Effect of Dynamic Potassium Change on In-Hospital Mortality, Ventricular
Arrhythmias, and Long-Term Mortality in STEMI.
AB - We evaluated the effect of serum potassium (K) deviation on in-hospital and long
term clinical outcomes in patients with ST-segment elevation myocardial
infarction who were normokalemic at admission. A total of 2773 patients with an
admission serum K level of 3.5 to 4.5 mEq/L were retrospectively analyzed. The
patients were categorized into 3 groups according to their K deviation:
normokalemia-to-hypokalemia, normokalemia-to-normokalemia, and normokalemia-to
hyperkalemia. In-hospital mortality, long-term mortality, and ventricular
arrhythmias rates were compared among the groups. In a hierarchical multivariable
regression analysis, the in-hospital mortality risk was higher in normokalemia-to
hypokalemia (odds ratio [OR] 3.03; 95% confidence interval [CI], 1.72-6.82) and
normokalemia-to-hyperkalemia groups (OR 2.81; 95% CI, 1.93-4.48) compared with
the normokalemia-to-normokalemia group. In a Cox regression analysis, long-term
mortality risk was also higher in normokalemia-to-hypokalemia (hazard ratio [HR]
3.78; 95% CI, 2.07-7.17) and normokalemia-to-hyperkalemia groups (HR, 2.97; 95%
CI, 2.10-4.19) compared with the normokalemia-to-normokalemia group. Ventricular
arrhythmia risk was also higher in normokalemia-to-hypokalemia group (OR 2.98;
95% CI, 1.41-5.75) compared with normokalemia-to-normokalemia group. The current
study showed an increased in-hospital ventricular arrhythmia and mortality and
long-term mortality rates with the deviation of serum K levels from normal
ranges.
PMID- 29962234
TI - Articular Cartilage Repair of the Pediatric and Adolescent Knee with Regard to
Minimal Clinically Important Difference: A Systematic Review.
AB - Objective To perform a systematic review of clinical outcomes following
microfracture (MFX), autologous chondrocyte implantation (ACI), osteochondral
allograft transplantation (OCA), and osteochondral autograft transplantation
system (OATS) to treat articular cartilage lesions in pediatric and adolescent
patients. We sought to compare postoperative improvements for each cartilage
repair method to minimal clinically important difference (MCID) thresholds.
Design MEDLINE, Web of Science, Scopus, and Cochrane Library databases were
searched for studies reporting MCID-validated outcome scores in a minimum of 5
patients <=19 years treated for symptomatic knee chondral lesions with minimum 1
year follow-up. One-sample t tests were used to compare mean outcome score
improvements to established MCID thresholds. Results Twelve studies reporting
clinical outcomes on a total of 330 patients following cartilage repair were
identified. The mean age of patients ranged from 13.7 to 16.7 years and the mean
follow-up was 2.2 to 9.6 years. Six studies reported on ACI, 4 studies reported
on MFX, 2 studies reported on OATS, and 1 study reported on OCA. ACI ( P < 0.001,
P = 0.008) and OCA ( P < 0.001) showed significant improvement for International
Knee Documentation Committee (IKDC) scores with regard to MCID while MFX ( P =
0.66) and OATS ( P = 0.11) did not. ACI ( P < 0.001) and OATS ( P = 0.010) both
showed significant improvement above MCID thresholds for Lysholm scores. MFX ( P
= 0.002) showed visual analog scale (VAS) pain score improvement above MCID
threshold while ACI ( P = 0.037, P = 0.070) was equivocal. Conclusions Outcomes
data on cartilage repair in the pediatric and adolescent knee are limited. This
review demonstrates that all available procedures provide postoperative
improvement above published MCID thresholds for at least one reported clinical
pain or functional outcome score.
PMID- 29962235
TI - Comparing neighborhood and state contexts for women living with and without HIV:
understanding the Southern HIV epidemic.
AB - In the South, people living with HIV experience worse health outcomes than in
other geographic regions, likely due to regional political, structural, and
socioeconomic factors. We describe the neighborhoods of women (n = 1,800) living
with and without HIV in the Women's Interagency HIV Study (WIHS), a cohort with
Southern sites in Chapel Hill, NC; Atlanta, GA; Birmingham, AL; Jackson, MS; and
Miami, FL; and non-Southern sites in Brooklyn, NY; Bronx, NY; Washington, DC; San
Francisco, CA; and Chicago, IL. In 2014, participants' addresses were geocoded
and matched to several administrative data sources. There were a number of
differences between the neighborhood contexts of Southern and non-Southern WIHS
participants. Southern states had the lowest income eligibility thresholds for
family Medicaid, and consequently higher proportions of uninsured individuals.
Modeled proportions of income devoted to transportation were much higher in
Southern neighborhoods (Location Affordability Index of 28-39% compared to 16-23%
in non-Southern sites), and fewer participants lived in counties where hospitals
reported providing HIV care (55% of GA, 63% of NC, and 76% of AL participants
lived in a county with a hospital that provided HIV care, compared to >90% at all
other sites). Finally, the states with the highest adult incarceration rates were
all in the South (per 100,000 residents: AL 820, MS 788, GA 686, FL 644). Many
Southern states opted not to expand Medicaid, invest little in transportation
infrastructure, and have staggering rates of incarceration. Resolution of racial
and geographic disparities in HIV health outcomes will require addressing these
structural barriers.
PMID- 29962236
TI - Employers' views on disability, employability, and labor market inclusion: a
phenomenographic study.
AB - PURPOSE: This study aims to increase our understanding of employers' views on the
employability of people with disabilities. Despite employers' significant role in
labor market inclusion for people with disabilities, research is scarce on how
employers view employability for this group. METHODS: This was a qualitative
empirical study with a phenomenographic approach using semi-structured interviews
with 27 Swedish employers from a variety of settings and with varied experience
of working with people with disabilities. RESULTS: The characteristics of
employers' views on the employability of people with disabilities can be
described as multifaceted. Different understandings of the interplay between
underlying individual-, workplace-, and authority-related aspects form three
qualitatively different views of employability, namely as constrained by
disability, independent of disability, and conditional. These views are also
characterized on a meta-level through their association with the cross-cutting
themes: trust, contribution, and support. CONCLUSIONS: The study presents a
framework for understanding employers' different views of employability for
people with disabilities as a complex internal relationship between conceived
individual-, workplace-, and authority-related aspects. Knowledge of the
variation in conceptions of employability for people with disability may
facilitate for rehabilitation professionals to tailor their support for building
trustful partnerships with employers, which may enhance the inclusion of people
with disabilities on the labor market. Implications for rehabilitation Employers'
views on employing people with disabilities vary with respect to individual-,
workplace-, and authority-related aspects in relation to trust, contribution and
support. Knowledge of the employers' views on the employability of people with
disabilities can support professionals in authorities and in vocational
rehabilitation. The findings illustrate the importance of analyzing what type of
support employers need as a starting point for building trustful partnerships
between authority actors and employers. The findings offer a vocabulary that can
be used by professionals in authorities and in vocational rehabilitation in
tailoring employer-oriented support to increase labor market inclusion of people
with disabilities.
PMID- 29962237
TI - Variation and diversity of the breakpoint sequences on 4AL for the 4AL/5AL
translocation in Triticum.
AB - The translocation of 4AL/5AL in Triticum, which occurred before the
differentiation of T. urartu and einkorn, is an important chromosomal
rearrangement. Recently, the first identification of breakpoint sequence on 4AL
for this translocation provides the opportunity to analyze the variation and
diversity of breakpoints in Triticum. In this study, the breakpoint regions of 52
accessions from 21 species were isolated and further characterized. The sequences
were divided into 12 types based on their lengths, which ranged from 2009 to 2552
bp. Cluster analysis showed that they were further divided into three groups.
Interesting evolutionary relationships among a few of the species were observed
and discussed. Multiple sequence alignment of the 52 sequences made it possible
to detect 13 insertion and deletion length polymorphisms (InDels) and 101 single
nucleotide polymorphisms (SNPs). Furthermore, several species- or accession
specific SNPs or InDels were also identified. Based on BLAST analysis of the
conserved sequences, the breakpoint was narrowed down to a 125 bp fragment. Taken
together, the results obtained in this study enrich our understanding of
chromosomal breakpoints and will be useful for the identification of other
breakpoints in wheat.
PMID- 29962238
TI - Characterization of parent-of-origin methylation using the Illumina Infinium
MethylationEPIC array platform.
AB - AIM: This study aimed to establish a catalog of probes corresponding to imprinted
differentially methylated regions (DMRs) on the Infinium HumanMethylationEPIC
BeadChip. MATERIALS & METHODS: Reciprocal uniparental diploidies with low normal
biparental mosaic contribution, together with normal diploid controls, were
subjected to EPIC BeadChip hybridization. The methylation profiles were assessed
for imprinted differential methylation. Top candidates were validated using locus
specific PCR-based assays. RESULTS: Seven hundred and eighty-nine CpG probes
coincided with 50 known imprinted DMRs and 467 CpG probes corresponding to 124
novel imprinted DMR candidates were identified. Validation led to identification
of several subtle DMRs within known imprinted domains as well as novel maternally
methylated regions associated with PTCHD3 and JAKMIP1. CONCLUSION: Our
comprehensive list of bona fide-imprinted DMR probes will simplify and facilitate
methylation profiling of individuals with imprinting disorders and is applicable
to other diseases in which aberrant imprinting has been implicated, such as
cancer and fetal growth.
PMID- 29962239
TI - Validation of a self-administered version of the Mediterranean diet scale (MDS)
for cardiac rehabilitation patients in Canada.
AB - The Mediterranean dietary pattern has been linked with lower incidence of
cardiovascular disease and the Mediterranean diet scale (MDS) has been created to
incorporate and test the inherent characteristics of this dietary pattern. This
study aimed to psychometrically validate a self-administered version of the MDS
in cardiac rehabilitation (CR) patients in Canada. To establish content validity,
the scale was reviewed by an expert interdisciplinary panel. A final version of
the tool was tested in 150 CR patients. Cronbach's alpha was 0.69. All ICC
coefficients met the minimum recommended standard. Factor analysis revealed four
factors, all internally consistent. Criterion validity was supported by
significant differences in total scores by duration in CR. Construct validity was
supported by agreements between the self-administered MDS and original MDS in all
items and with the 3-day food record in 8 of 13 items. In conclusion, the self
administered version of the MDS demonstrated good reliability and validity.
PMID- 29962240
TI - The acute effect of lower-limb warm-up on muscle performance.
AB - It has been purported that the mechanism for muscular improvement after a gluteal
warm-up protocol is likely to occur from neural activation. However, little is
known about whether changes in muscular performance are due to changes in muscle
activity. Therefore, the aim of this study was to determine whether a lower-limb
warm-up that targets the gluteal muscle group would improve countermovement jump
and short-distance sprinting through increased muscle activity. Ten semi
professional rugby union players (age 25.4 +/- 2.9 yr; height 1.83 +/- 6.7 m;
body mass 96.8 +/- 10.6 kg) with at least three years of resistance training
experience volunteered for the study. In a cross-over design, participants
performed countermovement jumps and 5 m sprints before and after a gluteal warm
up and a 10 min rest (control). Electromyography was used to measure muscle
activity of the gluteus maximus and biceps femoris. Countermovement jump height
significantly improved (7.9%, p < 0.05) after the lower-limb warm-up protocol
compared with the control (3.2%). There was a significant (p < 0.05) improvement
in sprint times over 2.5 m and 5 m regardless of the condition. There was no
significant change in the muscle activity in any of the conditions. The results
indicate that a lower-limb warm-up can acutely enhance countermovement jump
performance compared to a control.
PMID- 29962241
TI - Effect of coverage gap on healthcare utilization among Medicare beneficiaries
with chronic obstructive pulmonary disorder.
AB - OBJECTIVE: To evaluate the association between the Medicare coverage gap with
hospitalization, emergency room (ER) visits, and time to hospitalization in
chronic obstructive pulmonary disease (COPD) patients. METHODS: Retrospective
cohort study using data from a Medicare Advantage (MA) plan. Patients with >=1
claim for COPD at baseline, >=65 years, continuous 24-months enrollment and
without any cancer/end stage renal disease diagnosis were eligible. Patients not
reaching the coverage gap (no coverage gap) were matched and compared to those
reaching the coverage gap and those reaching catastrophic coverage in separate
analyses. Chi-square tests and Cox proportional hazards model were used to
compare outcomes across matched cohorts. RESULTS: In total, 3142 COPD patients
were identified (79% no coverage gap, 10% coverage gap, and 11% catastrophic
coverage). Compared to the no coverage gap group, a larger number of
beneficiaries in the coverage gap group had >=1 hospitalization (26% vs 32%, p <
.05), >= 1 ER visits (43% vs 49%, p < .05), and >=1 hospitalization/ER (total
visit) (47% vs 54%, p < .05), respectively. Compared to the no coverage gap
group, a greater number of beneficiaries in catastrophic coverage had >=1 ER
visit (45% vs 53%, p < .05) or >=1 total visits (48% vs 56%, p < .05),
respectively. Time to hospitalization was shorter among those entering the
coverage gap as compared to the no coverage gap [Hazards Ratio (HR) = 1.5; p =
.040]. CONCLUSIONS: COPD patients entering the coverage gap and catastrophic
coverage were associated with increased utilization of healthcare services.
Entering the coverage gap was also associated with shorter time to
hospitalization as compared to the no coverage gap.
PMID- 29962242
TI - IMPDH2 is highly expressed in breast cancer and predicts unfavourable prognosis.
AB - Inosine monophosphate dehydrogenase type II (IMPDH2) is reported to be associated
with tumor formation. However, the correlation between IMPDH2 and breast cancer
has never been reported. In this study, IMPDH2 expression was measured in 40
cases of breast cancer tissues and matched adjacent normal tissues by
quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting
assays. Then, IMPDH2 expression was further detected in 153 cases of breast
cancer tissues by immunohistochemistry (IHC). The correlation between IMPDH2
expression and clinicopathological characteristics and patients' prognosis was
investigated in breast cancer. Results shown that IMPDH2 mRNA level in breast
cancer tissues was significantly elevated compared with those in matched adjacent
normal tissues (P<0.001). The high-expression rate of IMPDH2 in breast cancer
tissues was 62.7%, which was significantly higher than those in adjacent normal
tissues (17.6%, P<0.001). IMPDH2 high expression correlated with lymph node
metastasis and TNM stage in breast cancer (P<0.05). Kaplan-Meier analysis
revealed that IMPDH2 as well as lymph node metastasis and TNM stage were
significantly associated with patients' prognosis (P<0.05). Multivariate Cox
regression analysis showed MPDH2, lymph node metastasis and TNM stage could be
served as independent factors to predict prognosis. Thus, these data indicate
IMPDH2 is highly expressed in breast cancer and predicts unfavourable prognosis,
which may be served as a potential biomarker.
PMID- 29962243
TI - Are UK hospital pharmacy departments ready for the rise of gene therapy medicinal
products?
AB - INTRODUCTION: The first gene therapy medicines are licensed and National
Institute for Health and Care Excellence approved for use in the NHS. UK Hospital
pharmacy departments will need to work with multidisciplinary colleagues to
ensure that there are facilities available to handle this new group of medicines.
Areas Covered: UK licensed and National Institute for Health and Care Excellence
gene therapy medicinal products (GTMP) and requirements for handling. Review of
pharmacy facilities and implementation of advanced therapy medicinal products
(ATMP) in the UK. Expert Opinion: Most hospital pharmacy departments do not have
aseptic facilities for the reconstitution of gene therapy medicines, or have the
appropriate freezers in place. Staff do not have the understanding or training of
these products unless they are experienced in using them in clinical trials.
Chief Pharmacists will need to ensure that governance process are in place as
they will ultimately be responsible for the implementation and safe handling of
these product. Therefore, work needs to continue to highlight the importance of
pharmacy departments and their role in the implementation of this new group of
medicines. As more GTMPs are licensed and become standard medicines being handled
in pharmacy departments, there will be more hospital pharmacy departments ready
to handle them. Initially it will just be the centers of excellence, ATMP
centers, and research centers with the expertise and facilities. In the long
term, other hospitals will plan and build the facilities they require.
PMID- 29962244
TI - Disability and corporeal (im)mobility: how interstate variation in Medicaid
impacts the cross-state plans and pursuits of personal care attendant service
users.
AB - PURPOSE: This paper addresses how Medicaid personal care attendant (PCA) service
users with physical disabilities experience barriers to cross-state movement
arising from the interstate variation in these programs. Using the Moves in
Context model, this analysis focuses on the structural-level influences on
individual cross-state move trajectories. METHODS: Semi-structured interviews
were conducted with 18 Medicaid PCA service users who were considering or
pursuing cross-state moves motivated by opportunity. Questions addressed the
cross-state move process; social participation; education and employment; and
access to PCA services. Grounded theory methods were used to analyze interview
transcripts and generate analytic codes and categories. FINDINGS: Participants
described their experiences with interstate variation in Medicaid PCA services in
terms of (1) contending with conflicts between the need for services and the
desire for cross-state moves; (2) navigating "hoops of fire"; and (3) recasting
imagined futures. Participants also expressed experiences of intrastate
confinement, or being stuck in their current state (4) using metaphors of
immobility and (5) recognizing intrastate confinement as a form of categorical
exclusion. CONCLUSION: Interstate variation in Medicaid PCA policy impedes
program users' ability to pursue educational and occupational advancement, and
leads to feelings of second-class citizenship. Policy changes should be explored
to affirm the autonomy of Medicaid PCA service users. Implications for
Rehabilitation Interstate variation in Medicaid PCA services and cross-state
moves * Medicaid personal care assistance service users desire and pursue cross
state moves, especially when drawn by educational or employment opportunities.
* Interstate variation in Medicaid policy negatively impacts the ability for PCA
service program users to pursue these moves due to gaps or delays in service
access, creating inequity in opportunity and feelings of second-class
citizenship. * Individual users of Medicaid PCA services need information and
services as they plan pursue cross-state moves. * States and the Center of
Medicare and Medicaid Services should offer guidance to support the independent
living, educational, and economic goals of users of PCA services who desire cross
state moves.
PMID- 29962245
TI - Comparative functional and pharmacological characterization of Sandoz proposed
biosimilar adalimumab (GP2017): rationale for extrapolation across indications.
AB - BACKGROUND: Biosimilars are approved biologics that match reference medicine in
quality, safety, and efficacy. The development of Sandoz proposed biosimilar
adalimumab (SPBA; GP2017) involved a target-directed, iterative state-of-the-art
quality-by-design development program. Here, we describe the functional and
pharmacological characterization of SPBA and its proposed mechanism of action in
immune-mediated inflammatory diseases. METHODS: Sensitive in vitro binding and
functional characterization studies, and nonclinical evaluations
(pharmacokinetics, pharmacodynamics, and safety/toxicology) were performed as
part of a stepwise approach to confirm the biosimilarity of SPBA with reference
adalimumab. RESULTS: Matching values were reported for SPBA and reference
adalimumab in binding assays involving tumor necrosis factor (TNF)-alpha,
complement 1q and human immune effector cell Fcgamma receptor subtypes in cell
based bioassays for Fc receptor function (complement- and antibody-dependent
cytotoxicity), and in apoptosis inhibition. Furthermore, SPBA and reference
adalimumab were equivalent in terms of membrane TNF binding and induction of
reverse signaling. Pharmacokinetics of SPBA and reference adalimumab were
comparable in rabbits, and the two biologics were equally effective in a human
TNF transgenic mouse model of polyarthritis. CONCLUSION: SPBA matches reference
adalimumab with regards to target binding, functional, pharmacokinetic, and
pharmacodynamic properties at the nonclinical level supporting its approval in
all indications of the reference adalimumab.
PMID- 29962246
TI - Next-generation sequencing and the impact on prenatal diagnosis.
AB - INTRODUCTION: The advent of affordable and rapid next-generation sequencing has
been transformative for prenatal diagnosis. Sequencing of cell-free DNA in
maternal plasma has enabled the development of not only a highly sensitive
screening test for fetal aneuploidies, but now definitive noninvasive prenatal
diagnosis for monogenic disorders at an early gestation. Sequencing of fetal
exomes offers broad diagnostic capability for pregnancies with unexpected fetal
anomalies, improving the yield and accuracy of diagnoses and allowing better
counseling for parents. The challenge now is to translate these approaches into
mainstream use in the clinic. Areas covered: Here, the authors review the current
literature to describe the technologies available and how these have evolved. The
opportunities and challenges at hand, including considerations for service
delivery, counseling, and development of ethical guidelines, are discussed.
Expert commentary: As technology continues to advance, future developments may be
toward noninvasive fetal whole exome or whole genome sequencing and a universal
method for noninvasive prenatal diagnosis without the need to sequence both
parents or an affected proband. Expansion of cell-free fetal DNA analysis to
include the transcriptome and the methylome is likely to yield clinical benefits
for monitoring other pregnancy-related pathologies such as preeclampsia and
intrauterine growth restriction.
PMID- 29962247
TI - Progesterone for treatment of symptomatic menopausal women.
AB - This review's purpose is to highlight evidence that oral micronized progesterone
(progesterone) is effective for hot flushes and night sweats (vasomotor symptoms,
VMS), improves sleep and is likely safe in menopausal women (who are more than 1
year since last menstruation). Methods include randomized controlled clinical
trials (RCT) supplemented with basic science, population and observational data
as needed. The barrier to use of progesterone is lack of awareness that safety
concerns with estrogen-including 'menopausal hormone therapy' (MHT) are not
applicable to progesterone. In a single 3-month RCT, progesterone (300 mg at
bedtime) was effective treatment of VMS in 133 healthy menopausal women. It
caused an overall 55% VMS decrease, no withdrawal-related VMS rebound and a
greater VMS decrease in 46 women with >=50 moderate-intense VMS/week.
Progesterone is equally or more effective than estradiol in improving
cardiovascular endothelial function and caused no cardiovascular safety concerns
in a 3-month RCT. An 8-year prospective cohort study (E3N) in more than 80 000
menopausal women showed progesterone prevented breast cancer in estrogen-treated
women. Multiple RCTs confirm that progesterone (300 mg daily at bedtime) does not
cause depression and improves deep sleep. In conclusion, progesterone effectively
treats VMS, improves sleep and may be the only therapy that symptomatic women,
who are menopausal at a normal age and without osteoporosis, need.
PMID- 29962248
TI - Central dislocation of femoral head without involvement of acetabular anterior
and posterior columns.
AB - Objective This study was performed to explore the treatment of central
dislocation of the femoral head without involvement of the acetabular columns.
Methods Preoperatively, a three-dimensionally printed model of the patient's
pelvis was manufactured according to the patient's computed tomography data. An
all-locking anatomical plate was designed based on the mirror of the ipsilesional
semi-pelvis. The fracture was reduced using reduction forceps and femoral
traction via the lateral rectus approach. The customized plate was used as a
template for reduction of the quadrilateral plate fracture. Results Reduction and
fixation of this patient's fracture was achieved with a customized all-locking
anatomical plate with a propeller shape via the lateral rectus approach.
Conclusions This report describes an isolated quadrilateral plate fracture with
central dislocation of the femoral head without involvement of the columns, which
is a rare injury that has not yet been classified. It was effectively treated
using a customized all-locking anatomical plate with propeller shape via the
lateral rectus approach.
PMID- 29962249
TI - HIV cure: global overview of bNAbs' patents and related scientific publications.
AB - INTRODUCTION: This article provides a global overview of patent deposits for
broadly neutralizing antibodies (bNAbs), which have emerged as a key strategy for
HIV cure and future HIV vaccines. Scientific and technological barriers to the
discovery of an effective HIV vaccine in the last 40 years have raised concerns
on the potential for relevant advances in this area. Nevertheless, recent
breakthrough studies have identified novel immune pathways for new innovative HIV
vaccine and HIV cure strategies. Areas covered: In our patent study, we have
identified in a global scale, in the last decade, a sharp increase in the number
of bNAbs' patent deposits related to HIV prevention and treatment strategies,
reaching 90 bNAbs in 2017, protected by 184 different patent deposits. Refining
our patent search to the different stages of bNAbs' development has also allowed
us to identify 12 of them already at clinical stage of research (VRC01, 10E8,
3BNC117, 10-1074, 2G12, 2F5, KD-247, 4E10, PG9, PGDM1400, PGT121, and VRC07). We
describe these recent breakthroughs and discuss the prospects and limitations of
these novel strategies. Expert opinion: Our results indicate the intellectual
property outcomes of a scientific revolution in this field, expressing innovative
modifications in antibodies to increase their potency and half-life, which have
resulted in extremely potent antibodies that could provide novel preventive and
therapeutic HIV strategies.
PMID- 29962250
TI - Malignant Otitis Externa Outcomes: A Study of the University HealthSystem
Consortium Database.
AB - OBJECTIVE: To characterize factors that affect outcomes for patients with
malignant otitis externa (MOE). METHODS: Retrospective review of inpatients with
MOE was performed. Patient demographics, comorbid conditions, complications,
procedures, and mortalities were analyzed. RESULTS: A total of 786 patients with
MOE were identified. The mean hospitalization length of stay (LOS) was 18.6 days
(SD = 19.7). The overall mortality rate was 2.5% (n = 20), and complication rate
was 4.3% (n = 34). Increasing age significantly and positively correlated with
the incidence of MOE (r = 0.979, P < .0001). Factors that were associated with an
increased rate of mortality were sepsis (odds ratio [OR] = 18.5; ES = 0.94; 95%
CI, 0.47-1.42), congestive heart failure (OR = 3.1; ES = 0.42; 95% CI, 0.02
0.82), weight loss (OR = 10.2; ES = 1.23; 95% CI, 0.61-1.85), and coagulopathy
(OR = 8.8; ES = 1.84; 95% CI, 0.91-2.77). Surgical intervention was performed in
19.2% (n = 151) of patients. Facial nerve involvement was present in 15.5% (n =
122) of patients and was associated with a significantly longer LOS of 12.9 days
(SD = 19.6; ES = 0.21; 95% CI, 0.03-0.41). CONCLUSIONS: This large multi
institutional database study of MOE demonstrates that several patient factors
impact the LOS and mortality. Patients at risk for unfavorable outcomes include
the elderly, male gender, comorbidities, or cranial nerve involvement.
PMID- 29962251
TI - Pancreatic function and histoarchitecture in Wistar rats following chronic
exposure to Bushfire(r): the mitigating role of zinc.
AB - Objectives To assess the toxicopathologic effects of chronic exposure to the
glyphosate-based herbicide Bushfire(r) on the pancreas of Wistar rats and the
protective role of zinc. Methods We exposed the rats to daily doses of 14.4 to
750 mg/kg body weight of the glyphosate-based herbicide Bushfire(r) and to 50 or
100 mg/kg zinc, and measured blood glucose levels and serum insulin levels.
Tissue samples were evaluated for histopathological alterations. Results Levels
of both blood glucose and serum insulin increased in glyphosate-exposed rats, and
moderate to severe degenerative changes were observed in both glandular
pancreatic acinar cells and islets of Langerhans in all rats exposed to
glyphosate. These effects were prevented by pretreatment with zinc. Conclusion
Chronic exposure to glyphosate can alter pancreatic function and
histoarchitecture, but zinc supplementation can mitigate these toxicopathologic
effects.
PMID- 29962252
TI - Probation and Parole Officers' Compliance With Case Management Tools:
Professional Discretion and Override.
AB - Actuarial assessment has become an integral component of offender management,
helping to structure the decision-making of correctional staff about offenders'
case plans. Despite research validating instruments and documenting best
practices in offender assessment, fewer studies explore how practitioners use
these diagnostic and case management tools. Using survey data from a sample of
probation and parole staff, the current study examines the influence of
professional characteristics, job burnout and stress, and supervision strategy
preferences on noncompliance with assessment data entry and deviations from the
tools' risk and needs recommendations. Results indicate various forms of
noncompliance with case management tools are fairly common. Staff with greater
tenure and heightened depersonalization and emotional exhaustion exhibit greater
odds of assessment noncompliance. Case managers who adopt surveillance and
rehabilitation supervisory tactics are less likely to deviate from the tools'
processes and results, while staff who prefer opportunity-reduction strategies
have increased odds of assessment noncompliance.
PMID- 29962253
TI - First reported bisphosphonate-related spontaneous oral-nasal fistula: a case
report.
PMID- 29962254
TI - Effect of mate tea (Ilex paraguariensis) on the expression of the leukocyte NADPH
oxidase subunit p47phox and on circulating inflammatory cytokines in healthy men:
a pilot study.
AB - Increased superoxide production by phagocytic NADPH oxidase has been associated
with inflammatory conditions. Growing evidences suggest that dietary polyphenols
may modulate the expression of NADPH oxidase subunits. Herein, we examined
whether soluble mate tea (SMT) consumption - a polyphenol-rich beverage - affects
the expression of the leukocyte NADPH oxidase protein p47phox and/or circulating
biomarkers of inflammation and antioxidant biomarkers in humans. In a two-phase
study, nine men were requested to drink water (control) for 8 d and then follow a
second 8-d period drinking SMT. Blood samples were analysed for p47phox protein
in CD16+/CD14- cells, interleukin (IL)-1beta (IL-1beta), tumour necrosis factor
alpha (TNF-alpha), IL-6, total phenols, and reduced and oxidised glutathione (GSH
and GSSG, respectively) after each study phase. After SMT intake, CD16+/CD14-
cells' p47phox protein and serum TNF-alpha and IL-6 levels were significantly
attenuated (P < .05) while plasma phenolic compounds and blood GSH:GSSG ratio
were significantly enhanced (P < .05). Consumption of SMT favourably affected
leukocytes' p47phox expression and inflammatory cytokine and antioxidants levels
in peripheral blood, which may help decrease oxidative stress and low-grade
inflammation.
PMID- 29962256
TI - Novel compound heterozygous PANK2 gene mutations in a Chinese patient with
atypical pantothenate kinase-associated neurodegeneration.
AB - AIM: Pantothenate-kinase-associated neurodegeneration (PKAN), which is
characterised by iron accumulation in the basal ganglia, is a rare autosomal
recessive neurodegenerative disorder caused by pantothenate kinase 2 (PANK2) gene
mutations. The PANK2 gene is located on chromosome 20p13 and encodes pantothenate
kinase. Herein, we identified one patient with PKAN who had mutations in the
PANK2 gene. MATERIALS AND METHODS: We performed clinical and radiographic
investigations, and diagnosed this disease at the clinical and genetic levels.
RESULTS: It is worth mentioning that the patient displayed an eye-of-the-tiger
sign. Through scanning the exons and flanking intronic sequences of PANK2 in
patient and control subjects, we report a compound heterozygote c. 260A > G
(NM_001324191) and c.405dupC (NM_153638) for PANK2 mutations in a Chinese patient
with clinical manifestation of progressive prosopospasm, dysarthria and gait
disturbance. Bioinformatics analysis showed that two variants exhibited highly
conserved residues across species. CONCLUSION: we reported a patient presenting
with atypical PKAN, and identified novel compound heterozygous PANK2 gene
mutations..
PMID- 29962255
TI - Defective autophagy in osteoblasts induces endoplasmic reticulum stress and
causes remarkable bone loss.
AB - Macroautophagy/autophagy is a highly regulated process involved in the turnover
of cytosolic components, however its pivotal role in maintenance of bone
homeostasis remains elusive. In the present study, we investigated the direct
role of ATG7 (autophagy related 7) during developmental and remodeling stages in
vivo using osteoblast-specific Atg7 conditional knockout (cKO) mice. Atg7 cKO
mice exhibited a reduced bone mass at both developmental and adult age. The
trabecular bone volume of Atg7 cKO mice was significantly lower than that of
controls at 5 months of age. This phenotype was attributed to decreased
osteoblast formation and matrix mineralization, accompanied with an increased
osteoclast number and the extent of the bone surface covered by osteoclasts as
well as an elevated secretion of TNFSF11/RANKL (tumor necrosis factor [ligand]
superfamily, member 11), and a decrease in TNFRSF11B/OPG (tumor necrosis factor
receptor superfamily, member 11b [osteoprotegerin]). Remarkably, Atg7 deficiency
in osteoblasts triggered endoplasmic reticulum (ER) stress, whereas attenuation
of ER stress by administration of phenylbutyric acid in vivo abrogated Atg7
ablation-mediated effects on osteoblast differentiation, mineralization capacity
and bone formation. Consistently, Atg7 deficiency impeded osteoblast
mineralization and promoted apoptosis partially in DDIT3/CHOP (DNA-damage
inducible transcript 3)- and MAPK8/JNK1 (mitogen-activated protein kinase 8)
SMAD1/5/8-dependent manner in vitro, while reconstitution of Atg7 could improve
ER stress and restore skeletal balance. In conclusion, our findings provide
direct evidences that autophagy plays crucial roles in regulation of bone
homeostasis and suggest an innovative therapeutic strategy against skeletal
diseases.
PMID- 29962257
TI - Progesterone for the prevention and treatment of osteoporosis in women.
AB - Estradiol (E2) is women's dominant 'bone hormone' since it is essential for
development of adolescent peak bone mineral density (BMD) and physiological
levels prevent the rapid (3-week) bone resorption that causes most adult BMD
loss. However, deceasing E2 levels trigger bone resorption/loss. Progesterone
(P4) is E2's physiological partner, collaborating with E2 in every cell/tissue;
its bone 'job' is to increase P4-receptor-mediated, slow (3-4 months)
osteoblastic new bone formation. When menstrual cycles are normal length and
normally ovulatory, E2 and P4 are balanced and BMD is stable. However, clinically
normal cycles commonly have ovulatory disturbances (anovulation, short luteal
phases) and low P4 levels; these are more frequent in teen and perimenopausal
women and increased by everyday stressors: energy insufficiency,
emotional/social/economic threats and illness. Meta-analysis shows that almost
1%/year spinal BMD loss occurs in those with greater than median (~31%) of
ovulatory disturbed cycles. Prevention of osteoporosis and fragility fractures
requires the reversal of stressors, detection and treatment of teen-to
perimenopausal recurrent cycle/ovulatory disturbances with cyclic oral micronized
progesterone. Low 'Peak Perimenopausal BMD' is likely the primary risk for
fragility fractures in later life. Progesterone plus estradiol or other
antiresorptive therapies adds 0.68%/year and may be a highly effective
osteoporosis treatment. Randomized controlled trials are still needed to confirm
progesterone's important role in women's bone formation.
PMID- 29962258
TI - Endovascular treatment of primary mycotic aortic aneurysms: a 7-year single
center experience.
AB - Objective This study was performed to assess the efficacy and outcome of
endovascular aneurysm repair (EVAR) for treatment of primary mycotic aortic
aneurysms (PMAAs). Methods Fourteen consecutive patients who presented with PMAA
from April 2010 to July 2017 were retrospectively reviewed. Preoperative,
intraoperative, and postoperative clinical data were recorded, and late infection
related complications and long-term survival were assessed. Results The aneurysms
were located in the abdominal aorta in 10 patients and in the left common iliac
artery in 4 patients. Positive microbial cultures were found in 12 patients,
including Salmonella species in 11 and Streptococcus in 1. The remaining two
patients had negative culture results. Ten patients received preoperative
antibiotics before elective EVAR for 7 +/- 9 days after admission. Four patients
who underwent emergent EVAR due to ruptured aneurysms were given their first dose
of antibiotics before EVAR. Three patients underwent surgical drainage, and six
underwent percutaneous drainage within 30 days after EVAR. No death occurred
within 30 days of the initial procedure. The mean follow-up was 34.8 (range, 3-84
months). One patient underwent re-intervention to resolve obstruction of the
iliac/femoral artery 5 months postoperatively. Relapse of infection occurred in
six patients (42.8%) during follow-up; infection-related death occurred in three
of these patients. The other patients recovered with either conversion to open
radical surgery or medical therapy. The actuarial 7-year survival after EVAR was
75.7%. Conclusions EVAR and aggressive antibiotic therapy might be suitable for
PMAAs. Favorable results may be typical for infection caused by Salmonella.
PMID- 29962259
TI - Sugammadex affects emergence agitation in children undergoing strabismus surgery.
AB - Objective Emergence agitation (EA) has a multifactorial origin, and the effect of
sugammadex on EA has not been established. We investigated the effect of
sugammadex on EA incidence and severity. Methods We performed a retrospective
study of children aged 1 to 13 years who underwent strabismus surgery. Patients
received sugammadex or conventional neuromuscular reversal agents. The primary
outcome variables were EA incidence and severity. Secondary outcome variables
were postoperative fentanyl use, postoperative nausea and vomiting, time from
reversal agent administration to extubation, time from the end of surgery to
arrival in the post-anesthesia care unit (PACU) and time spent in the PACU. We
used propensity score matching to eliminate baseline imbalances. Results Age,
sex, use of desflurane, and intraoperative fentanyl were significant predictors
of agitation severity using a multivariable analysis. Sugammadex did not
significantly affect EA in logistic regression and multiple regression analyses.
In the propensity-matched analysis, patients in the sugammadex group showed rapid
recovery, but there was no difference in the EA incidence or severity. Conclusion
Sugammadex did not affect EA incidence or severity compared with conventional
cholinesterase inhibitors, although it showed a favorable recovery profile in
children undergoing strabismus surgery.
PMID- 29962260
TI - Activity Patterns Associated With Health Status in Later Life Among Singaporeans.
AB - Research on activities overlooks the possibility that older adults engage in
different activities contemporaneously. To address this gap, we used latent class
analyses to identify activity patterns and then examined demographic and health
correlates of these patterns among a nationally representative sample of older
adults in Singapore. We identified four classes of activities: the family-focused
instrumental activity (FIA) class, the social leisure activity (SLA) class, the
multidynamic activity (MDA) class, and the passive activity (PA) class.
Furthermore, the MDA members showed higher scores in their mental health. Worse
physical functioning and higher depression scores also increased the likelihood
of being in the FIA and PA groups. Significant demographics such as gender,
ethnicity, marital status, education, employment, house type, and income were
related to heterogeneity in older adults' activity patterns. Service providers
might consider the impact of certain significant demographic and health-related
correlates when planning programs to ensure greater reach and access.
PMID- 29962261
TI - Safety and efficacy of total parenteral nutrition versus total enteral nutrition
for patients with severe acute pancreatitis: a meta-analysis.
AB - Objective This study was performed to systematically compare the safety and
efficacy of total enteral nutrition (TEN) and total parenteral nutrition (TPN)
for patients with severe acute pancreatitis (SAP). Methods The PubMed database
was searched up to January 2017, and nine studies were retrieved. These studies
were selected according to specific eligibility criteria. The methodological
quality of each trial was assessed, and the study design, interventions,
participant characteristics, and final results were then analyzed by Review
Manager 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen,
Denmark). Results Nine relevant randomized controlled trials involving 500
patients (244 patients in the TEN group and 256 patients in the TPN group) were
included in the meta-analysis. Pooled analysis showed a significantly lower
mortality rate in the TEN than TPN group [odds ratio (OR), 0.31; 95% confidence
interval (CI), 0.18-0.54]. The duration of hospitalization was significantly
shorter in the TEN than TPN group (mean difference, -0.59; 95% CI, -2.56-1.38).
Compared with TPN, TEN had a lower risk of pancreatic infection and related
complications (OR, 0.41; 95% CI, 0.22-0.77), organ failure (OR, 0.17; 95% CI,
0.06-0.52), and surgical intervention (OR, 0.17; 95% CI, 0.05-0.62). Conclusions
This meta-analysis indicates that TEN is safer and more effective than TPN for
patients with SAP. When both TEN and TPN have a role in the management of SAP,
TEN is the preferred option.
PMID- 29962262
TI - Low dose of uranium induces multigenerational epigenetic effects in rat kidney.
AB - PURPOSE: A protocol of chronic exposure to low dose of uranium was established in
order to distinguish the sexual differences and the developmental process that
are critical windows for epigenetic effects over generations. METHODS: Both male
and female rats were contaminated through their drinking water with a non-toxic
solution of uranyl nitrate for 9 months. The exposed generation (F0) and the
following two generations (F1 and F2) were examined. Clinical monitoring, global
DNA methylation profile and DNA methyltransferases (DNMTs) gene expression were
analyzed in kidneys. RESULTS: While the body weight of F1 males increased, a
small decrease in kidney and body weight was observed in F2 males. In addition,
global DNA hypermethylation profile in kidney cells was observed in F1 and F2
males. qPCR results reveal a significant increase of methyltransferase genes
expression (DNMT1 and DNMT3a) for F2 females. CONCLUSIONS: In the field of public
health policy and to raise attention to generational effects for the risk
assessment of the environmental exposures, low doses of uranium do not imply
clinical effects on adult exposed rats. However, our results confirm the
importance of the developmental windows' sensitivity in addition to the sexual
dimorphisms of the offspring.
PMID- 29962263
TI - Biguanides enhance antifungal activity against Candida glabrata.
AB - Candida spp. are the fourth leading cause of nosocomial blood stream infections
in North America. Candida glabrata is the second most frequently isolated
species, and rapid development of antifungal resistance has made treatment a
challenge. In this study, we investigate the therapeutic potential of metformin,
a biguanide with well-established action for diabetes, as an antifungal agent
against C. glabrata. Both wild type and antifungal-resistant isolates of C.
glabrata were subjected to biguanide and biguanide-antifungal combination
treatment. Metformin, as well as other members of the biguanide family, were
found to have antifungal activity against C. glabrata, with MIC50 of 9.34 +/-
0.16 mg/mL, 2.09 +/- 0.04 mg/mL and 1.87 +/- 0.05 mg/mL for metformin, phenformin
and buformin, respectively. We demonstrate that biguanides enhance the activity
of several antifungal drugs, including voriconazole, fluconazole, and
amphotericin, but not micafungin. The biguanide-antifungal combinations allowed
for additional antifungal effects, with fraction inhibition concentration indexes
ranging from 0.5 to 1. Furthermore, metformin was able to lower antifungal MIC50
in voriconazole and fluconazole-resistant clinical isolates of C. glabrata. We
also observed growth reduction of C. glabrata with rapamycin and an FIC of 0.84
+/- 0.09 when combined with metformin, suggesting biguanide action in C. glabrata
may be related to inhibition of the mTOR complex. We conclude that the biguanide
class has direct antifungal therapeutic potential and enhances the activity of
select antifungals in the treatment of resistant C. glabrata isolates. These data
support the further investigation of biguanides in the combination treatment of
serious fungal infections.
PMID- 29962264
TI - Depression, Executive Dysfunction, and Prior Economic and Social Vulnerability
Associations in Incarcerated African American Men.
AB - Low executive function (EF) and depression are each determinants of health. This
study examined the synergy between deficits in EF (impaired cognitive
flexibility; >75th percentile on the Wisconsin Card Sorting Test perseverative
error score) and depressive symptoms (modified Centers for Epidemiologic Studies
Depression) and preincarceration well-being among incarcerated African American
men ( N = 189). In adjusted analyses, having impaired EF and depression was
strongly associated with pre-incarceration food insecurity (odds ratio [ OR] =
3.81, 95% confidence interval [CI] = [1.35, 10.77]), homelessness ( OR = 3.00,
95% CI [1.02, 8.80]), concern about bills ( OR = 3.76, 95% CI [1.42, 9.95]), low
significant other support ( OR = 4.63, 95% CI [1.62, 13.24]), low friend support
( OR = 3.47, 95% CI [1.30, 9.26]), relationship difficulties ( OR = 2.86, 95% CI
[1.05, 7.80]), and binge drinking ( OR = 3.62, 95% CI [1.22, 10.80]). Prison
based programs to treat depression and improve problem-solving may improve
postrelease success.
PMID- 29962267
TI - Dose proportionality and pharmacokinetics of dronedarone following intravenous
and oral administration to rat.
AB - The aim of this study was to investigate the pharmacokinetic properties of
dronedarone by using noncompartmental analysis and modeling approaches after
intravenous and oral administration of dronedarone to rats. Twenty-eight male
Sprague-Dawley rats were randomly divided into four groups, and dronedarone was
administered intravenously (1 mg/kg) and orally (5, 10 and 40 mg/kg) based on a
parallel design. Blood samples were collected before and 0.083 (intravenous
administration only), 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h after drug
administration. The plasma concentration of dronedarone was determined by using
LC-MS/MS. The oral bioavailability of dronedarone was evaluated as approximately
16% in rats, similar to that in humans. The assessment of dose proportionality by
using the power model showed that AUCinf increased in a dose-proportional manner,
whereas AUC24h and Cmax exhibited a lack of dose proportionality over the dose
range between 5 and 40 mg/kg. The two-compartment model, with first-order
absorption and elimination rate constants, was sufficient to explain the
pharmacokinetics of dronedarone with biexponential decay. These findings will
help to understand the pharmacology of dronedarone to develop the new formulation
and therapeutics optimization linked to pharmacokinetic/pharmacodynamic study.
PMID- 29962266
TI - Suppression of autophagy and HCK signaling promotes PTGS2high FCGR3- NK cell
differentiation triggered by ectopic endometrial stromal cells.
AB - : Impaired NK cell cytotoxic activity contributes to the local dysfunctional
immune environment in endometriosis (EMS), which is an estrogen-dependent
gynecological disease that affects the function of ectopic endometrial tissue
clearance. The reason for the impaired cytotoxic activity of NK cells in an
ectopic lesion microenvironment (ELM) is largely unknown. In this study, we show
that the macroautophagy/autophagy level of endometrial stromal cells (ESCs) from
EMS decreased under negative regulation of estrogen. The ratio of peritoneal
FCGR3- NK to FCGR3+ NK cells increases as EMS progresses. Moreover, the autophagy
suppression results in the downregulation of HCK (hematopoietic cellular kinase)
by inactivating STAT3 (signal transducer and activator of transcription 3), as
well as the increased secretion of the downstream molecules CXCL8/IL8 and IL23A
by ESCs, and this increase induced the upregulation of FCGR3- NK cells and
decline of cytotoxic activity in ELM. This process is mediated through the
depression of microRNA MIR1185-1-3p, which is associated with the activation of
the target gene PTGS2 in NK cells. FCGR3- NK with a phenotype of PTGS2/COX2high
IFNGlow PRF1low GZMBlow induced by hck knockout (hck-/-) or 3-methyladenine (3
MA, an autophagy inhibitor)-stimulated ESCs accelerates ESC's growth both in
vitro and in vivo. These results suggest that the estrogen-autophagy-STAT3-HCK
axis participates in the differentiation of PTGS2high IFNGlow PRF1low GZMBlow
FCGR3- NK cells in ELM and contributes to the development of EMS. This result
provides a scientific basis for potential therapeutic strategies to treat
diseases related to impaired NK cell cytotoxic activity. ABBREVIATIONS: anti
FCGR3: anti-FCGR3 with neutralizing antibody; Ctrl-ESC: untreated ESCs; CXCL8: C
X-C motif chemokine ligand 8; ectoESC: ESCs from ectopic lesion; ELM: ectopic
lesion microenvironment; EMS: endometriosis; ESCs: endometrial stromal cells;
eutoESC:eutopic ESCs; HCK: hematopoietic cellular kinase; HCK(OE): overexpression
of HCK; IFNG: interferon gamma; IL23A (OE): overexpression of IL23A; KLRK1:
Killer cell lectin like receptor K1; MAP1LC3B/LC3B: microtubule-associated
protein 1 light chain 3 beta; 3 -MA: 3-methyladenine; 3-MA-ESC: 3-MA-treated
ESCs; MIR1185-1-3p+: overexpression of HsMIR1185-1-3p; NK: natural killer;
normESCs: normal ESCs; Rap-ESC:rapamycin-treated ESCs; PCNA: proliferating cell
nuclear antigen; PF: peritoneal fluid; SFKs: SRC family of cytoplasmic tyrosine
kinases; si-HCK: silencing of HCK; siIL23A: silencing of IL23A; USCs: uterus
stromal cells.
PMID- 29962265
TI - Induction of a Na+/K+-ATPase-dependent form of autophagy triggers preferential
cell death of human immunodeficiency virus type-1-infected macrophages.
AB - Although antiretroviral therapy is highly effective in suppressing human
immunodeficiency virus type-1 (HIV) replication, treatment has failed to
eliminate viral reservoirs and discontinuation of treatment results in viral
reactivation. Here, we demonstrate that peptides Tat-vFLIP-alpha2 and Tat-Beclin
1/BECN1 which have been shown to induce a Na+/K+-ATPase- and a
macroautophagy/autophagy-dependent form of cell death, autosis, can
preferentially kill HIV-infected macrophages while preventing virological
rebound. To improve bioavailability and drug delivery, Tat-vFLIP-alpha2 was
encapsulated into biodegradable PLGA (poly lactic-co-glycolic acid)-lipid-PEG
(polyethylene glycol) nanoparticles for long-lasting intracellular delivery.
After a single dose of NP-vFLIP-alpha2, HIV-infected macrophages were
preferentially killed in a dose-dependent manner compared to uninfected or
untreated HIV-infected cells with complete inhibition of HIV infection at 10 MUM
of peptide. HIV-infected macrophages treated with NP-vFLIP-alpha2 exhibited
increased markers of autophagy including LC3B lipidation, SQSTM1/p62 degradation
and Na+/K+-ATPase expression compared to untreated uninfected or infected cells.
Moreover, the increased cell death observed in HIV-infected cells was not altered
by treatment with bafilomycin A1 (BAF) or the caspase inhibitor Z-VAD-FMK, but
could be reversed following treatment with the Na+/K+-ATPase inhibitor, digoxin,
or knockdown of ATG5 or ATG7. NP-vFLIP-alpha2 induced preferential killing was
also detected in HIV-infected macrophages under antiretroviral suppression
without inducing viral reactivation. Additionally, we found that Na+/K+-ATPase
was upregulated in HIV-infected cells, which enhanced NP-vFLIP-alpha2 induced
cell death. These findings provide a novel strategy to eradicate HIV-infected
macrophages by selectively killing infected cells through the induction of Na+/K+
ATPase dependent autophagy, while preventing reactivation of virus and new
infection of uninfected bystander cells.
PMID- 29962268
TI - Risk of chemotherapy-induced febrile neutropenia with same-day versus next-day
pegfilgrastim prophylaxis among patients aged >=65 years: a retrospective
evaluation using Medicare claims.
AB - BACKGROUND: Two recent evaluations reported that risk of febrile neutropenia (FN)
may be higher when pegfilgrastim prophylaxis (PP) is administered on same day as
chemotherapy rather than per recommendation (1-3 days following chemotherapy).
Such evidence is based largely on the experience of younger privately insured
adults and may not be generalizable to older patients in US clinical practice.
METHODS: A retrospective cohort design and data from Medicare Claims Research
Identifiable Files (January 2008-September 2015) were employed. Patients were
aged >=65 years, had breast cancer or non-Hodgkin's lymphoma, received
chemotherapy with intermediate/high risk for FN, and received PP in >=1 cycle;
cycles with PP were stratified based on administration day (same-day ["Day 0"]
vs. 1-3 days following chemotherapy ["Days 1-3"]) and were pooled for analyses.
Adjusted odds ratios (ORs) for FN during the cycle were estimated for patients
who received PP on Day 0 versus Days 1-3. RESULTS: Study population included
65,003 patients who received PP in 261,184 cycles; in 5% of cycles, patients
received PP on Day 0. Incidence proportion for FN in cycle 1 was 11.4% for Day 0
versus 8.4% for Days 1-3; adjusted OR was 1.4 (p < .001). Incidence proportion
for FN when considering all cycles was 7.7% for Day 0 and 6.0% for Days 1-3;
adjusted OR was 1.3 (p < .001). Adjusted ORs when considering all cycles and only
inpatient FN episodes (1.3, p < .001) and the narrow definition for FN (1.5, p <
.001) were similar. CONCLUSIONS: Among Medicare patients receiving chemotherapy
and PP in US clinical practice, PP was administered before the recommended timing
in 5% of cycles and FN incidence was significantly higher in these cycles. Along
with prior research, study findings support recently updated US practice
guidelines indicating that PP should be administered the day after chemotherapy.
PMID- 29962270
TI - Perceptual learning and recognition confusion reveal the underlying relationships
among the six basic emotions.
AB - The six basic emotions (disgust, anger, fear, happiness, sadness, and surprise)
have long been considered discrete categories that serve as the primary units of
the emotion system. Yet recent evidence indicated underlying connections among
them. Here we tested the underlying relationships among the six basic emotions
using a perceptual learning procedure. This technique has the potential of
causally changing participants' emotion detection ability. We found that training
on detecting a facial expression improved the performance not only on the trained
expression but also on other expressions. Such a transfer effect was consistently
demonstrated between disgust and anger detection as well as between fear and
surprise detection in two experiments (Experiment 1A, n = 70; Experiment 1B, n =
42). Notably, training on any of the six emotions could improve happiness
detection, while sadness detection could only be improved by training on sadness
itself, suggesting the uniqueness of happiness and sadness. In an emotion
recognition test using a large sample of Chinese participants (n = 1748), the
confusion between disgust and anger as well as between fear and surprise was
further confirmed. Taken together, our study demonstrates that the "basic"
emotions share some common psychological components, which might be the more
basic units of the emotion system.
PMID- 29962269
TI - Balloon-Based Organ Retractor With Increased Safety and Reduced Invasiveness
During Video-Assisted Thoracoscopic Surgery.
AB - OBJECTIVES: In recent years, video-assisted thoracoscopic surgery (VATS) has
increasingly become the preferred technique for thoracic surgery. However, the
inherent characteristics of the lungs as large, soft, slippery, and delicate
creates difficulties for pulmonary surgery. In this article, we outline the
development and assessment of a balloon-based organ retractor for VATS via
collaboration between medical and engineering personnel. METHODS: A dry lab trial
and accompanying questionnaire assessment were performed by a group of thoracic
surgeons. Objective pressure measurements were obtained, and animal experiment on
pigs was performed. RESULTS: In the dry lab trial, use of the developed organ
retractor required significantly less time and resulted in fewer difficulties
than using a Cherry Dissector. The measured pressure per mm2 of the developed
retractor was clearly lower than that for the Cherry Dissector. The questionnaire
completed by the surgeons following the dry lab and animal experiments showed
that most of the surgeons (7 surgeons out of 9) were satisfied with the quality
of the balloon-based retractor based on a score of 3.13 +/- 0.28 (mean +/-
standard deviation) out of 4.0. During the animal experiment, the balloon-based
retractor provided stable and clear viewing with minimal need for adjustment.
CONCLUSION: This balloon-based retractor could contribute to increased safety and
less-invasive VATS.
PMID- 29962271
TI - The Health Impact of Experiences of Discrimination, Violence, and Immigration
Enforcement Among Latino Men in a New Settlement State.
AB - Among Latinos in the United States, particularly in new settlement states,
racial/ethnic discrimination, violence, and immigration enforcement contribute to
health disparities. These types of experiences were explored among Latino men in
North Carolina through quantitative assessment data ( n = 247). Qualitative in
depth interviews were also conducted with a subsample of Latino men who completed
the assessment ( n = 20) to contextualize quantitative findings. Participants
reported high rates of unfair treatment, discrimination or violence, and
questioning about their immigration status. Having been questioned about one's
immigration status was significantly associated with increased drug use (adjusted
odds ratio [AOR] = 2.16; 95% confidence interval [CI] [1.07, 4.38]) and increased
depressive symptoms (AOR = 2.87; 95% CI [1.07, 7.67]). Qualitative themes
included: reports of frequent discrimination based on immigration status,
race/ethnicity, and language; workplaces and police interactions as settings
where reported discrimination is most common and challenging; frequent violent
victimization; psychological consequences of experiences of discrimination and
violence and concerns related to immigration enforcement for Latino men and their
families; inter- and intra-community tensions; health-care services as safe
spaces; use of coping strategies; and system-level approaches for reducing
discrimination and violent victimization of Latinos. Findings point to the need
to address underlying causes of discrimination and violence toward Latinos,
particularly those related to immigration enforcement, to support health and well
being.
PMID- 29962273
TI - The Mobility Crime Triangle for Sexual Offenders and the Role of Individual and
Environmental Factors.
AB - This study-based on a national data set ( N = 1,447)-focuses on extrafamilial
sexual assaults and their mobility. Spatial information about the offender's
house, the victim's house, and the crime scene was combined in mobility crime
triangles. The findings reveal that most of the assaults fall in the categories
of total mobility (42.78%) and offender mobility (33.10%). Our results also show
the validity of the distance decay function with over 50% of aggressions
occurring within 3 km of the offender's house. The analysis did not reveal the
existence of buffer zones, probably due to the acquaintance between some of the
offenders and their victims. The evidence suggests that environmental risk
factors are more significant than individual ones when it comes to explaining the
variation among mobility patterns in sexual assaults. Offenders appear to adapt
their mobility patterns and modus operandi according to the environmental
constraints. Often, offenders choose their own or their victim's house as a safe
environment for performed sexual assault.
PMID- 29962272
TI - Reducing "I Don't Know" Responses and Missing Survey Data: Implications for
Measurement.
AB - BACKGROUND: "I don't know" (DK) responses are common in health behavior research.
Yet analytic approaches to managing DK responses may undermine survey validity
and researchers' ability to interpret findings. OBJECTIVE: Compare the usefulness
of a methodological strategy for reducing DK responses to 3 analytic approaches:
1) excluding DKs as missing data, 2) recoding them to the neutral point of the
response scale, and 3) recoding DKs with the mean. METHODS: We used a 4-group
design to compare a methodological strategy, which encourages use of the response
scale after an initial DK response, to 3 methods of analytically treating DK
responses. We examined 1) whether this methodological strategy reduced the
frequency of DK responses, and 2) how the methodological strategy compared to
common analytic treatments in terms of factor structure and strength of
correlations between measures of constructs. RESULTS: The prompt reduced DK
response frequency (55.7% of 164 unprompted participants vs. 19.6% of 102
prompted participants). Factorial invariance analyses suggested equivalence in
factor loadings for all constructs throughout the groups. Compared to excluding
DKs, recoding strategies and use of the prompt improved the strength of
correlations between constructs, with the prompt resulting in the strongest
correlations (.589 for benefits and intentions, .446 for perceived susceptibility
and intentions, and .329 for benefits and perceived susceptibility). LIMITATIONS:
This study was not designed a priori to test methods for addressing DK responses.
Our analysis was limited to an interviewer-administered survey, and interviewers
did not probe about reasons for DK responses. CONCLUSION: Findings suggest that
use of a prompt to reduce DK responses is preferable to analytic approaches to
treating DK responses. Use of such prompts may improve the validity of health
behavior survey research.
PMID- 29962274
TI - Effects of right ventricular septum or His-bundle pacing versus right ventricular
apical pacing on cardiac function: A systematic review and meta-analysis of
randomized controlled trials.
AB - Objective Recent studies have demonstrated that right ventricular apical (RVA)
pacing has a deleterious impact on left ventricular function, while right
ventricular septum (RVS) or His-bundle pacing (HBP) contribute to improvements in
cardiac function. A meta-analysis of randomized controlled trials (RCTs) was
conducted to compare the mid- and long-term effects of RVS and HB pacing versus
RVA pacing on cardiac function. Methods Eligible RCTs were identified by
systematically searching the electronic literature databases PubMed(r), Cochrane
Library, Embase(r) and Ovid(r). Results Seventeen articles ( n = 1290 patients)
were included in this meta-analysis, including 14 studies comparing the effects
of RVA and RVS pacing on cardiac function and three studies comparing HBP with
pacing at other sites. Compared with RVA pacing, RVS or HBP exhibited a higher
left ventricular ejection fraction (LVEF) (weighted mean difference 3.28; 95%
confidence interval 1.45, 5.12) at the end of follow-up. Conclusions RVS pacing
exhibited a higher LVEF after long-term follow-up than RVA pacing. RVS pacing
could replace the previously used RVA pacing as a better alternative with
improved clinical outcomes. However, there remains a need for larger RCTs to
compare the safety and efficacy of RVS with RVA pacing.
PMID- 29962276
TI - Effect of psychosocial interventions on the severity of premenstrual syndrome: a
meta-analysis.
AB - INTRODUCTION: Premenstrual syndrome (PMS) is common in women with reproductive
age and it affects the normal life. Psychosocial interventions are recommended
for some women who experience less severe PMS. So far, no meta-analyses have
investigated the effect of overall psychosocial interventions on the severity of
PMS as an outcome. This review aims to explore the effectiveness of psychosocial
intervention for PMS. METHODS: We performed a systematic literature search in
PubMED, CINAHL, EMbase and PsycINFO in December 2016, following methodological
guidelines outlined in the literature ( www.york.ac.uk/crd/ guidance). The
primary outcome was the severity of PMS. Data were pooled using a random-effects
meta-analysis model. RESULTS: Pooled effects of 11 psychosocial interventions (n
= 324) showed statistically significant beneficial effects on the severity of PMS
(SMD -0.29, 95% CI -0.45 to -0.13, I2 = 27%). Participants who received coping
skills training had significantly low severity of PMS than the control group (SMD
-0.53, 95% CI -0.77 to -0.28, p < .001, I2 = 3%). There were no effects found for
education program nor social support intervention. DISCUSSION: Psychosocial
interventions, especially coping skills training for women with PMS, were
effective in reducing the severity of PMS. However, needed caution due to the
small number of studies.
PMID- 29962275
TI - HIV-1 Tat increases BAG3 via NF-kappaB signaling to induce autophagy during HIV
associated neurocognitive disorder.
AB - The human immunodeficiency virus-1 (HIV-1) regulatory protein Tat plays an
important role during HIV-1-associated neurocognitive disorders (HAND) by
inducing neuronal autophagy. In this study, we used immunohistochemistry,
immunofluorescence, western blot, qRT-PCR, and RNA interference to elucidate the
involvement of Bcl-2-associated athanogene 3 (BAG3) in the pathogenesis of HIV-1
Tat-induced autophagy during HAND. We found that BAG3 expression is elevated in
astrocytes in frontal cortex of macaques infected with simian immunodeficiency
virus-human immunodeficiency chimeric virus (SHIV). In addition, in human primary
glioblastoma cells (U87), HIV-1 Tat upregulated BAG3 in an NF-kappaB-dependent
manner to induce autophagy. Importantly, suppression of BAG3 or inhibition of NF
kappaB activity reversed the HIV-1 Tat-induced autophagy. These results indicate
that HIV-1 Tat induces autophagy by upregulating BAG3 via NF-kappaB signaling,
which suggests BAG3 and NF-kappaB could potentially serve as novel targets for
HAND therapies.
PMID- 29962277
TI - Molecular characterization of plasmid-encoded blaTEM, blaSHV and blaCTX-M among
extended spectrum beta-lactamases [ESBLs] producing Acinetobacter baumannii.
PMID- 29962278
TI - Fabrication and characterization of hydroxypropyl guar-poly (vinyl alcohol)-nano
hydroxyapatite composite hydrogels for bone tissue engineering.
AB - Biocompatible bone implants composed of natural materials are highly desirable in
orthopedic reconstruction procedures. In this study, novel and ecofriendly
bionanocomposite hydrogels were synthesized using a blend of hydroxypropyl guar
(HPG), poly vinyl alcohol (PVA), and nano-hydroxyapatite (n-HA) under freeze-thaw
and mild reaction conditions. The hydrogel materials were characterized using
various techniques. TGA studies indicate that both composites, HPG/PVA and
HPG/PVA/n-HA, have higher thermal stability compared to HPG alone whereas
HPG/PVA/n-HA shows higher stability compared to PVA alone. The HPG/PVA hydrogel
shows porous morphology as revealed by the SEM, which is suitable for bone tissue
regeneration. Additionally, the hydrogels were found to be transparent and
flexible in nature. In vitro biomineralization study performed in simulated body
fluid shows HPG/PVA/n-HA has an apatite like structure. The hydrogel materials
were employed as extracellular matrices for biocompatibility studies. In vitro
cell viability studies using mouse osteoblast MC3T3 cells were performed by MTT,
Trypan blue exclusion, and ethidium bromide/acridine orange staining methods. The
cell viability studies reveal that composite materials support cell growth and do
not show any signs of cytotoxicity compared to pristine PVA. Osteoblastic
activity was confirmed by an increased alkaline phosphatase enzyme activity in
MC3T3 bone cells grown on composite hydrogel matrices.
PMID- 29962279
TI - Drug Development in Endometriosis and Adenomyosis: It Takes More Than Just Good
Science.
AB - The pipelines of pharmaceutical companies are filled with thousands of promising
new compounds for a plethora of indications. Yet, a close review of the drugs
that have recently been in clinical trials quickly reveals that only a handful of
drugs under evaluation in women with endometriosis can be genuinely qualified as
truly innovative and breakthrough drugs. Why is there such an industry-wide
lukewarm interest in drug research and development for endometriosis/adenomyosis?
Why are pharmaceutical companies so reluctant to initiate programs or invest in
academic research in endometriosis/adenomyosis? It is evident that a substantial
part of the novel druggable targets originate from research in academia. However,
only the pharmaceutical industry has the resources and expertise to bring drugs
to patients. In other words, we are fully dependent on the pharmaceutical
industry to bring new therapeutics to the market. The aim of this editorial is to
make scientists from academia aware of the enormous complexity of the drug
development process, the drivers that propel pharmaceutical companies to initiate
new programs and to prioritize their portfolios, the value of intellectual
property rights, and also about the importance of scientific rigor, predictive
translational models, and biomarkers. At the same time, the pharmaceutical
industry must be made aware of the enormous opportunity at hand, as the current
patient population with endometriosis/adenomyosis is just the tip of the iceberg.
We hope that the insights presented here will enable the
endometriosis/adenomyosis research community to find ways to valorize their
knowledge and attract the interest of the industry.
PMID- 29962280
TI - Concurrent validity and reliability of an iPhone app for the measurement of ankle
dorsiflexion and inter-limb asymmetries.
AB - The purpose of this investigation was to analyze the validity and reliability of
an iPhone app (named: Dorsiflex) for the measurement of weight-bearing ankle
dorsiflexion. To do this, twelve healthy participants (age=28.6+/-2.3 years)
performed a weight-bearing lunge test with each leg in five separate occasions,
while dorsiflexion angle was simultaneously registered using a professional
digital inclinometer and the Dorsiflex iPhone app, which was specifically
developed for this study. A total of 120 angles measured both with the digital
inclinometer and the app were then compared for validity, reliability and
accuracy purposes using several statistical tests. There was an almost perfect
correlation between the digital inclinometer and the Dorsiflex app for the
measurement of ankle dorsiflexion (r=0.989, 95% CI=0.986-0.993, SEE=0.48o), with
trivial, non-significant differences between devices (SMD=0.17, p=0.10). When
analyzing the reliability of the app for the measurement of five different trials
for each participant, similar coefficients of variation (CV) were observed in
comparison with those obtained with the digital inclinometer (Dorsiflex app:
CV=5.1+/-2.3 %; Digital inclinometer: CV=4.9+/-2.5 %). The results of the present
study show that weight-bearing ankle dorsiflexion can be easily, accurately, and
reliably evaluated using the Dorsiflex iPhone app.
PMID- 29962282
TI - Rapamycin inhibits activation of AMPK-mTOR signaling pathway-induced Alzheimer's
disease lesion in hippocampus of rats with type 2 diabetes mellitus.
AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is strongly correlated with
Alzheimer's disease (AD). Rapamycin has important uses in oncology, cardiology
and transplantation medicine. This study aims to investigate effects of rapamycin
on AD in hippocampus of T2DM rat by AMPK/mTOR signaling pathway. METHODS: Morris
water maze test was applied to evaluate the learning and memory abilities. The
fasting plasma glucose (FBG), glycosylated haemoglobin, total cholesterol,
triglyceride and serum insulin level were measured. RT-qPCR and Western blot
analysis were performed to test expression of AMPK and mTOR. Immunohistochemistry
was used to detect the Abeta deposition and immunoblotting to test the total tau,
p-tau and Abeta precursor APP expressions. RESULTS: After treated with rapamycin,
T2DM rats and rats with T2DM and AD showed increased learning-memory ability, and
decreased levels of FBG, glycosylated hemoglobin, total cholesterol, triglyceride
and serum insulin, decreased expression of APP and p-tau, increased AMPK mRNA
expression and p-AMPK and decreased Abeta deposition, mTOR mRNA expression and p
mTOR. CONCLUSION: The study demonstrated that rapamycin reduces the risk of AD in
T2DM rats and inhibits activation of AMPK-mTOR signaling pathway, thereby
improving AD lesion in hippocampus of T2DM rats.
PMID- 29962283
TI - Can Physicians Demonstrate High Quality Care Using Paternalistic Practices? A
Case Study of Paternalism in Latino Physician-Patient Interactions.
AB - We argue that patient autonomy is a cultural value specific to Western culture
and that the autonomy focus in U.S. health care may produce negative patient
outcomes for patients from other cultures. To this end, we present a case study
of a Mexican physician's interactions with his patients and apply the method of
discourse analysis to argue that (a) this physician's interactions are highly
paternalistic, (b) there is an appreciation for this among his Latino patients
and in the broader Latino community, and (c) this physician provides high-quality
ethical care precisely because his paternalism communicates important ethical
values such as familial intimacy, insistence, and care. We further propose that
paternalism may produce better outcomes for Latino patients.
PMID- 29962281
TI - Effectiveness and Safety of Simultaneous Integrated Boost-Proton Beam Therapy for
Localized Pancreatic Cancer.
AB - PURPOSE: To evaluate the clinical effectiveness and feasibility of simultaneous
integrated boost-proton beam therapy in patients with localized pancreatic
cancer. METHODS: Thirty-seven patients with localized pancreatic cancer underwent
simultaneous integrated boost-proton beam therapy, and 8 (21.6%) patients
received induction chemotherapy. The internal target volume was obtained by
summing the gross tumor volumes in exhalation phase computed tomography images.
Planning target volume 1 included internal target volume plus 3 to 5 mm margins,
excluding the 5 mm expanded volume of gastrointestinal structures, and planning
target volume 2 included the internal target volume plus 7 to 12 mm margins. The
prescribed doses to planning target volume 1 and planning target volume 2 were 45
GyE (equivalent dose in 2 Gy, 54.4 GyE10) and 30 GyE (equivalent dose in 2 Gy,
32.5 GyE10) in 10 fractions, respectively. RESULTS: Overall, treatment was well
tolerated, with no grade of toxicity >=3. Median overall survival was 19.3
months, and 1-year local progression-free survival, relapse-free survival, and
overall survival rates were 64.8%, 33.2%, and 75.7%, respectively. Patients
treated with simultaneous integrated boost-proton beam therapy after induction
chemotherapy had a significantly higher median overall survival time compared to
those with simultaneous integrated boost-proton beam therapy alone (21.6 months
vs 16.7 months, P = .031). Multivariate analysis showed that induction
chemotherapy was a significant factor for overall survival ( P < .05).
CONCLUSIONS: Simultaneous integrated boost-proton beam therapy could be feasible
and promising for patients with localized pancreatic cancer.
PMID- 29962284
TI - Drug carrier three-layer nanofibrous tube for vascular graft engineering.
AB - Currently available synthetic grafts demonstrate moderate success at the
macrovascular level, but there are still challenges at small vascular scale
(inner diameter of less than 6 mm). In this paper, silk fibroin (SF)/polyurethane
(PU)/SF three-layer drug carrier nanofibrous tubes were developed for blood
vessel repair with several advantages over existing designs. Our design consisted
of a bionic three-layer microtube that was synthesized from the drug carrier SF
and oligomeric proanthocyanidin nanofibers as the inner layer, PU nanofibers as
the middle layer, and SF nanofibers as the outer layer. The results suggested
that these three-layer tubes are attractive biocompatible materials for use as
vascular grafts.
PMID- 29962285
TI - Surgical Confirmation of Incomplete Treatment for Primary Papillary Thyroid
Carcinoma by Percutaneous Thermal Ablation: A Retrospective Case Review and
Literature Review.
AB - BACKGROUND: Recently, thermal ablation has been proposed for treating primary
papillary thyroid carcinoma (PTC), triggering an extensive debate. This study
aimed to analyze surgical outcomes of post-ablation cases to investigate the
effectiveness and safety of thermal ablation in primary PTC. METHODS: Primary PTC
patients treated with thermal ablation were retrospectively searched for from the
authors' medical record database prior to August 2017. The surgical patients met
the following criteria: (i) primary PTC treated with thermal ablation, (ii)
findings suspicious for malignancy of the post-ablation lesions on ultrasound or
malignancy confirmed by cytology, or with clinical evidence of cervical lymph
node metastasis (LNM), (iii) written informed consent for surgery, (iv)
preference for definite diagnosis of the post-ablation lesions for the patients
without evidence for malignant findings, and (v) tolerance of a thyroidectomy and
without severe illness. Moreover, a systematic review of the literature was made
to analyze relevant cases. RESULTS: Twelve patients with an average age of 41.0
+/- 13.6 years constituted the Fudan University Shanghai Cancer Center cohort in
this study. Twenty-two foci with a mean size of 1.3 +/- 0.7 cm were ablated
percutaneously under ultrasound guidance. Residual PTCs were confirmed in all
cases by histopathology, and LNM was present in 66.7% (8/12) of the patients.
Intraoperatively, adhesion of the post-ablation lesions with the strap muscles
was observed in six cases. Strap muscles were found to be cauterized in five
cases, and notably the recurrent laryngeal nerve was involved in one case.
Furthermore, seven relevant studies from Korea, Italy, and China were
retrospectively reviewed, and incomplete ablation of primary PTC and omission of
LNM by thermal ablation were observed frequently. CONCLUSIONS: Surgical therapy
demonstrated incomplete ablation of primary PTC and omission of LNM by thermal
ablation in this cohort of patients. Thermal ablation should be recommended with
caution as treatment of operable patients with primary PTC.
PMID- 29962286
TI - Randomized Controlled Trials of Interventions Addressing Intimate Partner
Violence in Sub-Saharan Africa: A Systematic Review.
AB - BACKGROUND: Intimate partner violence (IPV) perpetrated by males is the most
prevalent form of violence against women across the globe. A systematic review
was carried out to identify published randomized controlled trials of
interventions aiming to prevent or reduce IPV in Sub-Saharan Africa. Details were
sought on the interventions, outcomes, and risk of bias in evaluations. METHODS:
Articles were identified by searching MEDLINE, Embase, Web of Science, and
PsycInfo. The search included terms pertaining to IPV, the research design, and
the target geographical region. To be included, studies needed to have assessed
the impact of an intervention on reported incidence, prevalence of IPV, or
measures of related attitudes and behaviors. Fifteen papers were included in the
final review. Risk of bias was evaluated using the Cochrane Library "Risk of
Bias" tool. RESULTS: Findings suggest that interventions have the potential to
reduce IPV-related behaviors and attitudes. Certain types of IPV were more
amenable to change than others. Higher levels of efficacy were identified in
interventions that had longer follow-up, addressed IPV as a main aim, and
occurred at the community level or multiple levels of the social ecology.
CONCLUSIONS: Findings should be interpreted in light of varying risks of bias.
Suggestions are made for future research and practice.
PMID- 29962287
TI - High Immune Expression of Progesterone-Induced Blocking Factor in Epithelial
Ovarian Cancer.
AB - BACKGROUND: Progesterone-induced blocking factor, which is released from maternal
lymphocytes during pregnancy mediates the immune effect of progesterone.
According to new reports, it is suggested that proliferating cells, such as human
trophoblasts, mesenchymal stem cells, and malignant tumors, can excrete
progesterone-induced blocking factor at high ratio to escape from maternal
immunity. It is shown in recent studies that progesterone-induced blocking factor
is overexpressed in many malignant tumors such as breast, cervical, lymphoma, and
leukemia. There are no data about progesterone-induced blocking factor expression
in ovarian cancer cells. Hence, it is aimed to determine the progesterone-induced
blocking factor expression levels in epithelial ovarian cancer. METHODS: The
study which was a retrospective cross-sectional study was conducted in a
University Hospital. Twenty tissue specimens of patients with epithelial ovarian
cancer and 20 tissue specimens of patients with healthy ovary were included in
the study. Primary rabbit polyclonal anti- progesterone-induced blocking factor
antibody was used to incubate the sections at a ratio of 1:300. RESULTS: When the
tissue sections were compared based on immunostaining with progesterone-induced
blocking factor, we detected high stromal progesterone-induced blocking factor
expression in the epithelial ovarian cancer group as check against to the normal
ovarian group ( P = .007). Similarly, we found high glandular progesterone
induced blocking factor expression in the epithelial ovarian cancer group as
check against to the normal ovarian group ( P < .001). CONCLUSION: Proving the
existence of progesterone-induced blocking factor expression in epithelial
ovarian cancer cells may lead new visions or new studies for epithelial ovarian
cancer immunotherapy. As a result, epithelial ovarian cancer cells have greater
levels of expression of progesterone-induced blocking factor protein than normal
ovarian tissue according to immunohistochemistry. Further research is needed to
understand the clinical importance of this finding, to learn outcomes of high
levels of progesterone-induced blocking factor, and to investigate its underlying
mechanisms.
PMID- 29962288
TI - Bayesian quantile regression joint models: Inference and dynamic predictions.
AB - In the traditional joint models of a longitudinal and time-to-event outcome, a
linear mixed model assuming normal random errors is used to model the
longitudinal process. However, in many circumstances, the normality assumption is
violated and the linear mixed model is not an appropriate sub-model in the joint
models. In addition, as the linear mixed model models the conditional mean of the
longitudinal outcome, it is not appropriate if clinical interest lies in making
inference or prediction on median, lower, or upper ends of the longitudinal
process. To this end, quantile regression provides a flexible, distribution-free
way to study covariate effects at different quantiles of the longitudinal outcome
and it is robust not only to deviation from normality, but also to outlying
observations. In this article, we present and advocate the linear quantile mixed
model for the longitudinal process in the joint models framework. Our development
is motivated by a large prospective study of Huntington's disease where primary
clinical interest is in utilizing longitudinal motor scores and other early
covariates to predict the risk of developing Huntington's disease. We develop a
Bayesian method based on the location-scale representation of the asymmetric
Laplace distribution, assess its performance through an extensive simulation
study, and demonstrate how this linear quantile mixed model-based joint models
approach can be used for making subject-specific dynamic predictions of survival
probability.
PMID- 29962289
TI - Effects of precompression time and strength on the physical characteristics of
quasi-stapled porcine small intestinal tissue.
AB - Precompression is vital when performing gastrointestinal anastomosis with
staplers. However, research on the internal changes in intestinal tissue under
stapling is lacking, and the effects of precompression have not been clarified.
In this study, a stapler was modified, and the multifrequency bioimpedance of
porcine small intestinal tissue was measured from before clamping the tissue with
the stapler until the release of the tissue after precompression without firing.
The Cole Y model was fitted to the bioimpedance, and the changes in the tissue
were analyzed using the model parameters: G0, extracellular fluid conductance,
and Delta G, intracellular fluid conductance. The results show that the changes
of G0 and Delta G could be divided into four stages: rapid decrease, slow
decrease, intense resilience, and slow recovery. During slow decrease stage,
there was a greater decrease of G0 and Delta G (1.02E-05 +/- 1.12E-05 S and 1.73E
05 +/- 2.12E-05 S in precompression time's increase, 1.68E-05 +/- 8.74E-06 S and
1.20E-05 +/- 1.09E-05 S in precompression strength's increase). On the contrary,
during intense resilience stage, there was a less increase of G0 and Delta G
(0.88E-05 +/- 4.86E-05 S and 9.15E-05 +/- 9.37E-05 S in precompression time's
increase, 2.72E-05 +/- 3.53E-05 S and 1.02E-04 +/- 8.54E-05 S in precompression
strength's increase). In conclusion, the effects of precompression factors on
tissue have been preliminary revealed: the tissue under precompression becomes
thinner and less resilient. To improve the precompression effects and reduce any
excessive pressure exerted on the staples by tissue resilience, the
precompression time and strength should be increased appropriately.
PMID- 29962290
TI - Depression and Perspectives of Nigerian Immigrant Men in the United States: An
Applied Ethnographic Study.
AB - INTRODUCTION: Depression is among the most serious health problems experienced by
immigrants. Research has not sufficiently explored the perspectives of immigrant
men from male-dominant cultures on depression. The purpose of this study was to
describe the perspectives of Nigerian immigrant men in the United States on
depression and to determine whether their perceptions differ from those of their
female counterparts of a previous study. METHOD: Focused applied ethnography was
used to explore the perspectives of a purposeful sample of 18 Nigerian immigrant
men in Houston, Texas, and analyze the data using a thematic approach. RESULTS:
The overarching theme was, "Depression does not exist in the Nigerian culture."
The participants denied the existence of depression. Gender differences were not
noted in their perception of depression. DISCUSSION: The participants perceived
depression differently from the U.S. dominant culture and may not receive
adequate screening or treatment for depression, supporting the extant call for
recognition of cultural differences in health care.
PMID- 29962291
TI - Effects of DO on N2O emission during biological nitrogen removal using aerobic
granular sludge via shortcut simultaneous nitrification and denitrification.
AB - Dissolved oxygen (DO) is an important factor influencing biological nitrogen
removal. This study investigated the effects of different DO concentrations (4,
2, 1 mg/L) on nitrous oxide (N2O) production and nitrogen removal via shortcut
simultaneous nitrification and denitrification by aerobic granular sludge (SNDAG)
using a sequencing bath reactor. The results showed that N2O production was
highest (127.6 mg/m3) at a DO concentration of 2 mg/L; this was 24.17 and 2.90
times the production at DO concentrations of 4 and 12 mg/L, respectively. The
removal efficiency of total nitrogen also was the highest (61.68%) when the DO
concentration was 2 mg/L, compared to 35.22% and 50.65% at DO concentrations of 4
and 1 mg/L, respectively. The efficiency of the SNDAG process reached 53.86% at a
DO concentration of 2 mg/L, which was 1.33 and 1.67 times the efficiencies at DO
concentrations of 4 and 1 mg/L, respectively. Therefore, reducing the DO
concentration benefited the SNDAG process, but increased the emission of N2O.
PMID- 29962292
TI - Estimation of weekly intake of cadmium and lead by consumption of commercial
ready-to-feed infant foods.
AB - The purpose of this survey was to estimate the safety of ready-to-eat infant
foods in terms of Pb and Cd content. The studied samples were ready-to-eat infant
products: dinners (n = 74), soups (n = 27) and desserts (n = 82) containing
components of animal origin: meat and/or milk. Cd and Pb content was determined
using a GF-AAS method. The analysed products contained 1.82-3.54 ug Pb and 1.32
1.50 ug Cd per kg. The content of Pb per kg of the product can be represented as
dinners > soups > desserts, whereas the content of Cd was dinners > desserts >
soups. The analysed ready-to-eat products could be regarded as safe, because they
supply 12-month-old infants with Pb in an amount accounting for nearly 22% BMDL01
and Cd accounting for ca. 8.6% of the total weekly intake.
PMID- 29962293
TI - On the dynamics of one-prey-n-predator impulsive reaction-diffusion predator-prey
system with ratio-dependent functional response.
AB - In this paper, a one-prey-n-predator impulsive reaction-diffusion periodic
predator-prey system with ratio-dependent functional response is investigated. On
the basis of the upper and lower solution method and comparison theory of
differential equation, sufficient conditions on the ultimate boundedness and
permanence of the predator-prey system are established. By constructing an
appropriate auxiliary function, the conditions for the existence of a unique
globally stable positive periodic solution are also obtained. Examples and
numerical simulations are presented to verify the feasibility of our results. A
discussion is conducted at the end.
PMID- 29962294
TI - Stem Cell-Induced Pulp Regeneration Can Be Enhanced by Administration of CCL11
Neutralizing Antibody in the Ectopic Tooth Transplantation Model in the Aged
Mice.
AB - OBJECTIVE: Pulp regeneration by stem cell transplantation declines due to age
related reduction. We hypothesized that administration of a cytokine together
with the cell transplantation may improve the stem cell niche microenvironment
and promote regeneration. CCL11 is implicated as a factor in aging. This
investigation was performed to investigate the changes in the quality of the
regenerated pulp by administration of CCL11 antibody in the aged mice and
elucidate the underlying mechanisms. MATERIALS AND METHODS: Mobilized dental pulp
stem cell (MDPSC) transplants were characterized in an ectopic tooth root
transplantation model in both the aged and young mice. The amount of regenerated
pulp tissue was analyzed in the transplants with continuous administration of
CCL11 antibody compared with those without the antibody administration. Blood
CCL11 levels were assessed at the onset of the experiment. Furthermore,
immunostaining of CD68 together with CD11c or CD206 for M1 and M2 macrophage,
respectively, were performed. Each double-positive cell count of M1 and M2
macrophages and M1/M2 ratio in the transplants with administration were compared
with those without administration both in the aged and young mice. RESULTS: The
administration of CCL11 antibody enhanced pulp regeneration and significantly
reduced the blood CCL11 level in the aged mice. As the number of M1 macrophages
decreased, the M1/M2 ratio in the treated aged mouse was less than that in the
untreated aged mouse. There was, however, significant difference between the
treated aged mouse and the untreated young mouse. CONCLUSION: CCL11 antibody has
the potential to enhance and stimulate pulp regeneration in the aged mice.
PMID- 29962295
TI - Decision Time.
PMID- 29962296
TI - National variation between clinical commissioning groups in referral criteria for
primary total hip replacement surgery.
AB - The referral criteria used by the UK clinical commissioning groups for primary
total hip replacement surgery appear inconsistent; the criteria rarely follow
National Institute for Health and Care Excellence criteria. With established
guidelines available, it is unclear why the clinical commissioning groups have
referral criteia with less evidence base, without obviously addressing particular
issues in their locality.
PMID- 29962297
TI - Urinary schistosomiasis presented as bladder malignancy with pulmonary
metastases: a case report.
AB - Schistosoma haematobium is the species primarily responsible for the
manifestation of schistosomiasis in the genitourinary tract. It is a parasitic
disease caused by flukes (trematodes) of the genus Schistosoma, which can result
in acute and chronic manifestation. We report a case of urinary schistosomiasis
that initially presented as advanced bladder cancer with pulmonary metastasis on
initial computed tomography scan. Further investigations revealed no cancer and
pulmonary changes resolved with treatment. The involvement of bladder is the
hallmark of S. haematobium infection and it is unusual to have pulmonary
manifestation without concurrent hepatosplenic disease. Within the lungs,
deposition of Schistosoma eggs causes a granulomatous reaction, typically
producing miliary nodules on chest radiographs. In our case, this was interpreted
initially as lung metastases. However, given the cystoscopic findings and
subsequent resolution with praziquantel, this was proved otherwise. This case
highlights the importance of urinary cytology in the initial investigation of
haematuria. Clinicians should be aware of such a potential differential
diagnosis, especially in patients with prior travel history to endemic areas.
PMID- 29962298
TI - The effect of consultant outcome publication on surgeon behaviour: a systematic
review and narrative synthesis.
AB - Introduction Surgeon-specific outcome data, or consultant outcome publication,
refers to public access to named surgeon procedural outcomes. Consultant outcome
publication originates from cardiothoracic surgery, having been introduced to US
and UK surgery in 1991 and 2005, respectively. It has been associated with an
improvement in patient outcomes. However, there is concern that it may also have
led to changes in surgeon behaviour. This review assesses the literature for
evidence of risk-averse behaviour, upgrading of patient risk factors and
cessation of low-volume or poorly performing surgeons. Materials and methods A
systematic literature review of Embase and Medline databases was performed
according to the Preferred Reporting Items for Systematic Reviews and Meta
Analysis guidelines. Original studies including data on consultant outcome
publication and its potential effect on surgeon behaviour were included. Results
Twenty-five studies were identified from the literature search. Studies
suggesting the presence of risk-averse behaviour and upgrading of risk factors
tended to be survey based, with studies contrary to these findings using
recognised regional and national databases. Discussion and conclusion Our review
includes instances of consultant outcome publication leading to risk-averse
behaviour, upgrading of risk factors and cessation of low-volume or poorly
performing surgeons. As UK data on consultant outcome publication matures,
further research is essential to ensure that high-risk patients are not
inappropriately turned down for surgery.
PMID- 29962300
TI - Current use of procedure specific consent forms for laparoscopic cholecystectomy.
AB - Introduction Procedure specific consent forms (PSCFs) have been shown to improve
consenting practice for a standardised list of complications. The aim of this
study was to assess the current usage and quality of PSCFs in the National Health
Service (NHS) for cholecystectomy, specifically comparing the listed
complications with those mentioned on the NHS website. Methods A freedom of
information request was sent to all NHS trusts asking whether they perform
laparoscopic cholecystectomy and whether they have a PSCF for this. A copy of the
PSCF was also requested. Complications stated on these forms were compared with
those on the NHS Choices website. Results Overall, 162 (88%) of the 185 trusts
responded, with 121 of these performing cholecystectomies. Among these, 20 (17%)
currently use PSCFs; all provided a copy. Five (25%) of the PSCFs contained all
eight risks mentioned on the NHS website. The number of risks listed varied from
4 to 18 per form. Only bile duct injury was listed on every PSCF. The least
frequently mentioned complication (45% of forms) was the risk from general
anaesthetic. Conclusions This study suggests that too few trusts are using PSCFs
and that those PSCFs that are in use contain too little detail on the risks of
cholecystectomy. The listed risks and incidences on each PSCF were highly
variable. More trusts should begin to use PSCFs during the informed consent
process and each PSCF should include a nationally standardised list of potential
complications to act as a prompt for discussion (and documentation) of risk.
PMID- 29962299
TI - Morbidity in parathyroid surgery for renal disease is under reported: a
comparison of outcomes with primary hyperparathyroidism.
AB - Introduction Parathyroidectomy is considered to be a safe procedure with low
morbidity. However, while this is true for primary hyperparathyroidism, whether
it applies to tertiary disease is not so well documented. The aim of this study
was to assess the morbidity of surgery for tertiary hyperparathyroidism compared
with primary disease and to establish whether there are predictive factors for
poor outcomes. Methods Data for patients subjected to parathyroidectomy during
the period 2007-2015 were retrospectively analysed from a prospectively collected
database. Patient age, sex, American Society of Anesthesiologists (ASA) score,
renal status, extent of operation and indications for surgery were examined. The
complication and mortality rate were compared and independent predictors of
outcome were examined. Results A total of 1079 patients were scheduled for a
parathyroidectomy during the study period of whom 158 for renal related
hyperparathyroidism (renal group) and 921 for primary disease (non-renal group).
There was a significantly higher complication rate in the renal parathyroid
group, including a higher mortality (1.3% vs 0.1%, P = 0.011), overall
complication rate (7.0% vs 2.3%, P = 0.001), surgery related complication rate
(4.4% vs 1.7%, P = 0.03) and systemic complication rate (2.5% vs 0.4%, P =
0.005). In patients with ASA score <= 2 reoperative surgery (OR 9.25, 95%
confidence interval, CI 1.41-60.75), male sex (OR 4.12, 95% CI 1.46-11.63) and
renal impairment were (OR 5.86, 95% CI 1.65-20.78) were predictors of worse
outcomes. In patients with ASA score >=3 renal impairment, in addition to other
variables, were not predictors of complications. Conclusions Parathyroidectomy in
renal-related disease is associated with a significantly higher risk of morbidity
and mortality compared with primary hyperparathyroidism.
PMID- 29962301
TI - Shooting up? Analysis of 182 gunshot injuries presenting to a London major trauma
centre over a seven-year period.
AB - Introduction Metropolitan Police data, and those from the emergency department at
a London major trauma centre show a resurgence in gun crime. The aim of this
study was to collect data on all gunshot injuries over a seven-year period at
South-East London's trauma hub. Materials and methods This was a retrospective
observational study of all gunshot injuries between 1 January 2010 and 31
December 2016 at a London major trauma centre. Information regarding patient
demographics, morbidity and mortality was collected. Data from the English
indices of multiple deprivation were reviewed in relation to shooting locations
and socioeconomic status in South-East London. Results A total of 182 patients
from 939,331 emergency admissions presented with firearm injuries. Males
comprised 178 (97.8%) victims and 124 (68.1%) were documented as being Black or
Afro-Caribbean. The median age was 22 years. Some 124 (71.7%) victims were shot
within a 4 km radius of the hospital. The mean indices of multiple deprivation
decile ranking in shooting locations compared with non-shooting locations was 2.6
(+/- 0.1384) and 3.8 (+/- 0.1149), respectively. A total of 122 (67.0%) patients
underwent specialist operative intervention and 111 (61.0%) suffered only
superficial or musculoskeletal injuries. Six patients required emergency
thoracotomies; three (50.0%) survived to discharge. The median length of stay was
4 days (interquartile range 2-9 days) and 35 (24.0%) were admitted to intensive
care. Ten (5.5%) patients died. Discussion and conclusion Firearms injuries are
increasing and place a significant burden on hospital resources. Care provided to
gunshot victims has improved as a result of recent trauma management initiatives
at South-East London's major trauma centre.
PMID- 29962302
TI - Effectiveness of Health and Safety Training in Reducing Occupational Injuries
Among Harvesting Forestry Contractors in KwaZulu-Natal.
AB - Forestry work is generally characterized by a combination of personal and
environmental risks in health and safety. Employers need to ensure intensive and
continuous safety training to mitigate these risks; however, the efficacy of this
training is seldom evaluated. The aim of this study was to assess the
effectiveness of health and safety training in reducing injuries and improving
knowledge, attitudes, and perceptions toward safety among forestry workers in
KwaZulu-Natal (KZN), South Africa. A descriptive cross-sectional study was
conducted among 300 harvesting contract workers employed at a forestry company in
KZN. A questionnaire to assess the efficiency of health and safety training was
administered. In addition, a retrospective review of the injury register and
medical records of employees who sustained work-related injuries from 2009 to
2013 was completed. The company injury data for harvesting contractors reported
68 lost-time injuries during postcommencement of training. Slip, trip, and fall
injuries were the most reported cause of injuries, particularly among manual
harvesters. Respondents who were male, younger in age, and with less experience
had an increased risk of occupational injury. Most participants displayed
adequate knowledge of safety and were able to translate training into practice.
The health and safety training initiative was successful in reducing injuries and
increasing workers' awareness of, and responsibility for, health and safety
issues.
PMID- 29962303
TI - Effect of rutin on cisplatin-induced damage in human mesangial cells via
apoptotic pathway.
AB - Cisplatin (CP) is one of the most effective and widely used compounds in the
treatment of disease, including cancer, but is known to induce toxicity in
patients. Rutin (RUT) is a flavonoid glycoside from Sophora japonica L. that has
been shown to possess antioxidative, anti-inflammatory, and antiviral properties.
RUT is also known to attenuate cardiotoxicity, isoproterenol-induced cardiac
fibrosis, and ischemia/reperfusion-associated hemodynamic alteration, and
prevents high glucose-induced renal glomerular endothelial hyperpermeability. In
this study, we investigated the effect of RUT on CP-induced nephrotoxicity. CP
was used to induce toxicity in human mesangial cells (HMCs), HMCs were pretreated
with different concentrations of RUT before being exposed to 10 MUg/mL of CP. A
positive group was pretreated with antioxidant agent N-acetylcysteine prior to CP
administration. At doses between 12.5 and 25 MUM, RUT prevented CP-induced
reduction in cell viability. Treatment with RUT suppressed intracellular reactive
oxygen species and malonic dialdehyde levels and inhibited cell apoptosis. RUT
reversed the CP-induced upregulation of p53, cleaved-caspase-3, and increased pro
caspase-3 and pro-caspase-9 levels. In conclusion, the RUT can relieve CP-induced
nephrotoxicity by inhibiting the p53/caspase signaling pathway.
PMID- 29962304
TI - Effects of Moringa oleifera leaf powder on metabolic syndrome induced in male
Wistar rats: a preliminary study.
AB - Objective To evaluate the preventive effects of Moringa oleifera on metabolic
syndrome (MS) in male Wistar rats. Methods MS was induced by feeding rats a high
fat diet and drinking water containing 10% fructose for 6 weeks. In the
preventive group, M. oleifera was orally administered for 3 weeks prior to the
induction of MS, while in the treatment group, M. oleifera was administered for 3
weeks after the onset of MS. The treatment groups were compared with a control
group of untreated rats with induced MS. Fasting glucose, oral glucose tolerance,
insulin tolerance, total cholesterol, triglycerides, abdominal circumference, and
systolic and diastolic blood pressure were measured before and after MS induction
and/or M. oleifera treatment. Results After the induction of MS, the control
group had higher fasting glucose levels than the preventive group. No significant
differences were observed in insulin tolerance, oral glucose tolerance,
cholesterol, triglycerides, abdominal circumference, or systolic or diastolic
blood pressure. Compared with untreated controls, rats in the treatment group had
significantly improved glucose tolerance, triglycerides, and abdominal
circumference. Conclusions M. oleifera treatment attenuates MS in Wistar rats.
PMID- 29962305
TI - Dissemination of cfr-mediated linezolid resistance among Staphylococcus species
isolated from a teaching hospital in Beijing, China.
AB - Objective The aim of the present study was to report the dissemination of cfr and
fexA genes mediated by linezolid resistance among Staphylococcus species. Methods
Three methicillin-resistant staphylococci that were collected from a teaching
hospital in Beijing were identified as linezolid-resistant. These three
staphylococci were Staphylococcus aureus, S. haemolyticus, and S. cohnii.
Mutations in domain V of 23S ribosomal RNA, ribosomal proteins, and the cfr,
fexA, and optrA genes were analysed. Results The three isolates had no mutations
of 23S ribosomal RNA, but showed mutations in the cfr and fexA genes. Mutations
in the gene for ribosomal protein L3, which resulted in the amino acid exchanges
Gly108Glu, Ser158Phe, and Asp159Tyr, were identified in S. cohnii X4535.
Conclusions This is the first report of the cfr gene in clinical linezolid
resistant methicillin-resistant S. aureus isolated from Beijing. L3 mutations
coupled with the cfr and fexA genes may act synergistically. Potential
transmissibility of this agent, even without prior exposure to linezolid, may
have serious epidemiological repercussions.
PMID- 29962306
TI - Adaptation in Delivering Integrated Care: The Tension Between Care and Evidence
Based Practice.
AB - Clinical practice is assumed to be informed and supported by evidence-based
clinical research. Nonetheless, clinical practice often deviates from the
research evidence base, sometimes leading and sometimes lagging. Two examples
from integrated care in mental health care (care for serious mental illness and
collaborative mental health care in primary care settings) illustrate the natural
space and therefore tension between evidence and implementation that needs to be
better understood. Using the tools and perspectives of both examples, the authors
present a framework for the connected relationship between practice and research
that is founded on measurement and uses iterative adaptation guided by oversight
of and feedback from the stakeholders in this process.
PMID- 29962307
TI - Predicting Barriers to Treatment for Depression in a U.S. National Sample: A
Cross-Sectional, Proof-of-Concept Study.
AB - OBJECTIVE: Even though safe and effective treatments for depression are
available, many individuals with a diagnosis of depression do not obtain
treatment. This study aimed to develop a tool to identify persons who might not
initiate treatment among those who acknowledge a need. METHODS: Data were
aggregated from the 2008-2014 U.S. National Survey on Drug Use and Health
(N=391,753), including 20,785 adults given a diagnosis of depression by a health
care provider in the 12 months before the survey. Machine learning was applied to
self-report survey items to develop strategies for identifying individuals who
might not get needed treatment. RESULTS: A derivation cohort aggregated between
2008 and 2013 was used to develop a model that identified the 30.6% of
individuals with depression who reported needing but not getting treatment. When
applied to independent responses from the 2014 cohort, the model identified 72%
of those who did not initiate treatment (p<.01), with a balanced accuracy that
was also significantly above chance (71%, p<.01). For individuals who did not get
treatment, the model predicted 10 (out of 15) reasons that they endorsed as
barriers to treatment, with balanced accuracies between 53% and 65% (p<.05 for
all). CONCLUSIONS: Considerable work is needed to improve follow-up and retention
rates after the critical initial meeting in which a patient is given a diagnosis
of depression. Routinely collected information about patients with depression
could identify those at risk of not obtaining needed treatment, which may inform
the development and implementation of interventions to reduce the prevalence of
untreated depression.
PMID- 29962308
TI - Trends in and Predictors of Long-Term Antipsychotic Polypharmacy Use Among Ohio
Medicaid Patients with Schizophrenia, 2008-2014.
AB - OBJECTIVE: The study examined trends and patterns in long-term antipsychotic
polypharmacy among Ohio Medicaid patients with schizophrenia and predictors of
use. METHODS: A study using a retrospective cohort design and Medicaid claims
data was conducted for a cohort of 25,062 adults with a schizophrenic disorder
receiving antipsychotic medication between 2008 and 2014. Long-term antipsychotic
polypharmacy was defined as simultaneous treatment with two or more antipsychotic
medications for >=90 days. Annual trends in antipsychotic polypharmacy were
estimated. Multivariate logistic regression was used to identify patient
demographic, clinical, and treatment characteristics associated with
antipsychotic polypharmacy. RESULTS: The prevalence of antipsychotic polypharmacy
decreased significantly from 29.5% in 2008 (2,715 of 9,211) to 24.9% in 2014
(2,866 of 11,500) (adjusted odds ratio=.98, 99% confidence interval=.97-.99,
p<.001). Factors significantly associated with antipsychotic polypharmacy
included younger age, male sex, disabled status, rural residence, a schizophrenic
disorder other than schizoaffective disorder, a greater number of general medical
comorbidities, treatment with more psychotropic medication classes, and more
outpatient mental health treatment and emergency department visits. Antipsychotic
polypharmacy was significantly less likely for African Americans or those from
other racial minority groups compared with whites, for those with substance use
disorders compared with others, and for those with a greater number of inpatient
psychiatric hospitalizations. CONCLUSIONS: Antipsychotic polypharmacy declined
for pharmacologically treated individuals with schizophrenia in Ohio Medicaid
between 2008 and 2014, but it remained inordinately prevalent given existing
treatment guidelines that recommend antipsychotic monotherapy as the standard of
care for patients with schizophrenia.
PMID- 29962309
TI - Factors That Predict the Use of Psychotropics Among Children and Adolescents With
PTSD: Evidence From Private Insurance Claims.
AB - OBJECTIVE: This study aimed to determine which characteristics of youths with
posttraumatic stress disorder (PTSD) were associated with receiving prescriptions
for antidepressants, antipsychotics, or benzodiazepines. METHODS: A 2011-2012
retrospective cohort of children and adolescents with a new episode of PTSD was
extracted from medical and pharmacy claims from a nationally representative
sample of privately insured persons. Multivariate logistic regression assessed
attributes (demographic characteristics, mental and general medical
comorbidities, insurance arrangements, specialty type, and geographic location)
associated with utilization of antidepressants, antipsychotics, and
benzodiazepines. RESULTS: Among 7,726 youths with a new episode of PTSD in 2012,
just less than 60% received psychotherapy alone, about 6% received
pharmacotherapy, and about 35% received neither psychotherapy nor
pharmacotherapy. Among utilizers of medications, 71.3% used antidepressants and
21.6% used antipsychotics. Youths prescribed medication tended to be older and
have more general medical and mental comorbidities. Provider specialty, capitated
insurance arrangements, and more comorbidities predicted being prescribed
antidepressants. History of hospitalization, noncapitated insurance arrangements,
nonuse of psychotherapy, and more comorbidities predicted being prescribed
antipsychotics. Antidepressants and antipsychotics were more likely to be used in
the South. CONCLUSIONS: Only three-fifths of youths with PTSD received first-line
treatment (psychotherapy). More than one in 20 received pharmacotherapy, which
appeared to be associated with the most severe and complex presentations. More
than one-third of youths with PTSD received neither therapy nor medication,
signaling compromised quality of care. Future research should confirm the factors
associated with pharmacotherapy prescription and explore ways to increase the use
of psychotherapy in primary care.
PMID- 29962310
TI - A Systematic Review of the Attributes and Outcomes of Peer Work and Guidelines
for Reporting Studies of Peer Interventions.
AB - A SYSTEMATIC REVIEW OF THE ATTRIBUTES AND OUTCOMES OF PEER WORK.
PMID- 29962311
TI - Interventions to reduce inappropriate prescribing of antibiotics for acute
respiratory tract infections: summary and update of a systematic review.
AB - Objective Antibiotic overuse contributes to antibiotic resistance and adverse
consequences. Acute respiratory tract infections (RTIs) are the most common
reason for antibiotic prescribing in primary care, but such infections often do
not require antibiotics. We summarized and updated a previously performed
systematic review of interventions to reduce inappropriate use of antibiotics for
acute RTIs. Methods To update the review, we searched MEDLINE(r), the Cochrane
Library (until January 2018), and reference lists. Two reviewers selected the
studies, extracted the study data, and assessed the quality and strength of
evidence. Results Twenty-six interventions were evaluated in 95 mostly fair
quality studies. The following four interventions had moderate-strength evidence
of improved/reduced antibiotic prescribing and low-strength evidence of no
adverse consequences: parent education (21% reduction, no increase return
visits), combined patient/clinician education (7% reduction, no change in
complications/satisfaction), procalcitonin testing for adults with RTIs of the
lower respiratory tract (12%-72% reduction, no increased adverse consequences),
and electronic decision support systems (24%-47% improvement in appropriate
prescribing, 5%-9% reduction, no increased complications). Conclusions The best
evidence supports use of specific educational interventions, procalcitonin
testing in adults, and electronic decision support to reduce inappropriate
antibiotic prescribing for acute RTIs without causing adverse consequences.
PMID- 29962312
TI - Concerns About the headspace Model of Youth Mental Health Services.
PMID- 29962313
TI - To Prevent Suicide, Address It Directly.
PMID- 29962314
TI - Reaching for the Golden Goose Egg.
PMID- 29962315
TI - Concerns About the headspace Model of Youth Mental Health Services.
PMID- 29962316
TI - The Healing Relationships in Public-Sector Psychiatry.
PMID- 29962317
TI - PHQ-9 Administration in Outpatient Adolescent Psychiatry Services.
PMID- 29962318
TI - A qualitative study using semi-structured interviews of palliative care patients'
views on corneal donation and the timing of its discussion.
AB - BACKGROUND: Corneal transplantation can lead to sight restoration, but globally
there is a donor shortage. Many palliative care patients can donate their corneas
but think they are ineligible due to comorbidities. Healthcare professionals are
reluctant to broach the topic, but studies have shown that relatives would be
upset if they were not offered this chance. There is no existing research
involving patients. AIM: To understand the views and feelings of patients in
palliative care settings towards corneal donation and explore their opinions
regarding the timing of its discussion. DESIGN: This is an exploratory study
based at one UK palliative care unit. A census sampling method was used. Nine
participants took part in semi-structured interviews and thematic analysis was
undertaken. RESULTS: Themes found included altruistic motivation and the value of
sight. Family views were important, but the influence on final decisions varied.
The timing of discussion relative to the illness trajectory was important;
patients want to be able to engage fully in conversations and had concerns about
not being able to think clearly when closer to death. Participants also
associated discussion of donation as an indication of a poor prognosis. Patients
prefer face-to-face discussions with someone whom they had a close rapport. Many
had misconceptions about eligibility. CONCLUSION: This is the first study to
engage directly with palliative care patients and to establish their views on the
timing of corneal donation discussions. Patients are willing to discuss donation,
and further exploration of patient views in this area should be undertaken.
PMID- 29962319
TI - Acute pain disrupts prospective memory cue detection processes.
AB - Prospective memory refers to the planning, retention, retrieval, and execution of
intentions for future behaviours and it is integral to the enterprise of daily
living. Although prospective memory relies upon retrospective memory and
executive processes often disrupted by pain, limited research has explored the
influence of acute or chronic pain on the ability to complete prospective memory
tasks. In the present study we investigated the influence of acute pain on
prospective memory tasks that varied in their demands on executive processes
(i.e., non-focal versus focal prospective memory cues). Complex-span working
memory tasks were also administered to examine whether individual differences in
working memory capacity moderated any negative impact of pain on prospective
memory. Acute pain significantly impaired prospective memory performance in
conditions that encouraged non-focal strategic processing of prospective memory
cues, but not in conditions that encouraged more spontaneous focal processing.
Individual differences in working memory capacity did not moderate the effect of
acute pain on non-focal prospective memory. These findings provide new insights
into prospective memory dysfunction created by painful experiences.
PMID- 29962320
TI - Effect of Treadmill Walking on Leg Muscle Activation in Parkinson's Disease.
AB - Treadmills are often used as rehabilitation devices to improve gait in
Parkinson's disease (PD). Kinematic differences between treadmill and overground
gait have been reported. However, electromyographic (EMG) patterns during
treadmill and overground walking have not been systematically compared. The aim
of this study was to assess the effects of treadmill gait on the magnitude of the
EMG activity of the lower limb muscles in PD. We measured EMG activity of the
tibialis anterior, gastrocnemius medialis, vastus lateralis, and biceps femoris
of nine individuals with PD and nine healthy matched controls. Comparisons
between walking overground with walking on a treadmill and with walking with a
treadmill simulator were carried out. The treadmill simulator is a device that
simulates treadmill conditions with the exception of the belt. Our results have
shown that treadmill walking is associated with several EMG differences compared
with overground walking. The key finding of the study is that coactivation of the
thigh muscles was significantly decreased (37%; p = 0.008) in PD subjects when
walking on the treadmill in comparison with overground walking. The changes
observed in the coactivation level may be related to the belt movement, since no
changes were reported during walking with the treadmill simulator. Understanding
the differences between treadmill and overground gait as well as the mechanisms
that result in improvement of gait disturbances may optimize rehabilitative
protocols for patients with PD.
PMID- 29962321
TI - PD-1 blockade potentially enhances adoptive cytotoxic T cell potency in a human
acute myeloid leukaemia animal model.
AB - OBJECTIVES: Acute myeloid leukaemia (AML) is a malignant haematological disease
that remains difficult to cure. Cytotoxic T cell (CTL) adoptive infusion therapy
may be conducive to tumour remission by boosting physical immunity. Furthermore,
programmed death receptor-1 (PD-1) blockade immunotherapy has shown tremendous
success in many cancer therapies. METHOD: We attempted to combine these two
immunotherapy strategies to intervene in AML by generating AML cellspecific
cytotoxic T lymphocytes in vitro and in vivo with an AML cell strain expressing
specific antigens. RESULTS: First, we observed that peripheral blood mononuclear
cells (PBMCs) could be induced to generate large numbers of CD8+ CTL cells
through immune stimulation. In addition, these CD8+ cells could effectively
recognize a human AML cell line and exert cytotoxicity. In animal tests, PD-1
blockade combined with CTL infusion could induce significantly more AML tumour
reduction than either treatment alone. This synergistic effect was thought to be
connected to immune modulation enhancement, as regulatory T cells (Tregs) in the
peripheral blood (PB) were found to be suppressed. CONCLUSIONS: This finding
suggested the potential application of PD-1 blockade in AML. The present work
demonstrated an excellent synergistic tumour therapeutic effect of PD-1 blockade
and CTL therapy compared with either treatment alone.
PMID- 29962322
TI - The Effects of Light and Moderate Intensity Exercise on the Femoral Bone and
Cerebellum of d-Galactose-Exposed Rats.
AB - Aging causes the degeneration of organs of the locomotor system, including the
cerebellum and bones. Exercise may reverse this deterioration. d-galactose has
been frequently used in rodents to accelerate aging. The present study aimed at
investigating the effects of exercise on cerebellar and serum growth factors,
motor activity, and the number of bone cells of the femoral head of d-galactose
treated rats. Twenty-four male Wistar rats were divided randomly into four
groups, that is, three treated groups injected with 300 mg/(mL.kg) body weight
(bw) d-galactose solution daily for 4 weeks, and a control group injected with
normal saline. Following the 4-week administration of d-galactose solution, two
of the treated groups performed light- (45% VO2max) and moderate- (55% VO2max)
intensity exercise, by running on a treadmill 4 * a week for 4 weeks. Locomotor
activity was examined in rotarod and open field tests. The cerebellar and serum
Insulin-like Growth Factor 1 (IGF-1) and Brain-Derived Neurotrophic Factor (BDNF)
levels were measured using enzyme-linked immunosorbent assay (ELISA). The number
of osteoblasts and osteoclasts of femoral head was estimated using unbiased
stereological methods. It was found that the number of osteoclasts was higher in
the d-galactose-treated group than the normal control and moderate-intensity
exercise groups. No significant difference between groups was found in the
rotarod and open field test performance, IGF-1 and BDNF levels, as well as number
of osteoblasts. In conclusion, a 4-week administration of high-dosed-galactose
caused the increase of the number of osteoclasts. A subsequent 4-week moderate
intensity exercise reversed this increase to the normal level.
PMID- 29962323
TI - Does hypothyroidism augment sun-induced skin damage?
AB - OBJECTIVES: We investigated the mutual effects of overt hypothyroidism and
prolonged sunlight exposure on free radical accumulation and oxidative skin
damage. METHODS: Free radical accumulation was evaluated by monitoring the
transformation of 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide
(MTT) into MTT-formazan. The pro-oxidant enzymes xanthine oxidase (XO) and NADPH
diaphorase were measured in the skin. XO activity was estimated based on the
yield of uric acid, while NADPH-diaphorase reactivity was monitored
histochemically as an indirect marker of nitric oxide synthase and nitric oxide
activity. Cellular damage was determined by malondialdehyde formation, a marker
for lipid peroxidation. RESULTS: In the skin of both euthyroid and hypothyroid
animals, solar simulated ultraviolet irradiance increased the activity of XO and
the NADPHdiaphorase reactivity as a protective response to formation of free
radicals, such as reactive oxygen or nitrogen species. These pro-oxidant enzymes
diminished in hypothyroid rats. Accumulation of the same amount of free radicals
led to similar peroxidation in both hypothyroid and irradiated euthyroid rats.
Hypothyroid skin after UV-exposure showed even greater lipid peroxidation.
DISCUSSION: The hypothyroid state could be a risk factor for enhanced oxidative
skin damage in chronic photo-exposed skin due to oxidative stress. The lipid
peroxidation is one of the major pathways by which photo-oxidative stress
promotes photocarcinogenesis and photo-aging.
PMID- 29962324
TI - Optimization of Taylor spatial frame half-pins diameter for bone deformity
correction: Application to femur.
AB - Using external fixtures for bone deformity correction takes advantages of less
soft tissue injury, better bone alignment and enhances strain development for
bone formation on cutting section, which cause shorter healing time. Among these
fixtures, Taylor spatial frame is widely used and includes two rings and six
adjustable struts developing 6 degrees of freedom, making them very flexible for
this type of application. The current study describes a method to optimize Taylor
spatial frame pin-sizes currently chosen from the surgeon's experiences. A three
dimensional model of femur was created from computed tomography images;
segmentation of the medical images was made based on the Hounsfield unit (gray
scale) in order to allocate adequate mechanical properties into cortical and
trabecular bone sections. Both the cortical and trabecular sections were assumed
to be isotropic and homogeneous. The diameter optimization of Taylor spatial
frame's half-pins was carried out by coupling genetic algorithm and finite
element analysis. The finite element analysis was based on a static mechanical
load corresponding to a standing person's body weight. Finite element analysis
results were validated with experimentally measured strains obtained from bone
compression tests. A cost function, based on the developed bone stresses, was
defined close to the Taylor spatial frame's half-pins. The calculated cost
function showed a decrease of over 33% from the initial half-pin selection by the
surgeon and the genetic algorithm optimization. Consequently, the maximum
stresses experienced by the bone in the connected location of the half-pins
decreased from 121.4 MPa in the surgeon's selection to 73.07 MPa as a result of
the optimization process.
PMID- 29962325
TI - Are re-injured ligaments equivalent mechanically to injured ligaments: The role
of re-injury severity?
AB - The consequences of ligament re-injury have received limited attention. Although
the mechanical properties of injured ligaments improve over time, these
properties are never fully recaptured, rendering these injured ligaments
susceptible to re-injury. Previous injury is a significant risk factor for
recurrent injury, and this re-injury can result in longer absence from activity
than the initial injury. A rabbit medial collateral ligament model was used to
compare mechanically re-injured right medial collateral ligaments to injured left
medial collateral ligaments. Two groups of different re-injury severity were
investigated: 'minor' re-injury comparing transection re-injured right medial
collateral ligaments to transection injured left medial collateral ligaments;
'major' re-injury comparing gap re-injured right medial collateral ligaments to
transection injured left medial collateral ligaments. Initial injuries for both
groups were right medial collateral ligament transections 1 week before re
injury. After 5-6 weeks of healing, mechanical testing was performed to determine
(dimensionally) cross-sectional area; (structurally) medial collateral ligament
laxity, failure load, and stiffness; and (materially) cyclic creep strain and
failure stress. Because we wanted to evaluate whether the mechanical properties
of re-injured ligaments were equivalent or, at least, no worse than injured
ligaments, we used equivalence/noninferiority testing. This approach evaluates a
research hypothesis of equivalence, rather than difference, and determines
whether comparisons are 'statistically equivalent', 'noninferior', or
'potentially inferior'. Transection re-injured and gap re-injured ligaments were
'statistically equivalent' structurally to transection injured ligaments.
Transection re-injured ligaments were 'noninferior' both materially and
dimensionally to transection injured ligaments. Gap re-injured ligaments were
'potentially inferior' both materially and dimensionally to transection injured
ligaments. Two differences between the re-injuries, which affect healing, may
explain the mechanical outcomes: the presence or lack of healing products and the
proximity of ligament ends at the time of re-injury. Our findings suggest that
(in the short term) there is a severity of re-injury below which there is no
additional disadvantage to the healing process, mechanical behaviour, and
resulting potential for re-injury.
PMID- 29962326
TI - Comparison of the volumetric composition of lamellar bone and the woven bone of
calluses.
AB - Woven tissue is mainly present in the bone callus, formed very rapidly either
after a fracture or in distraction processes. This high formation speed is
probably responsible for its disorganized microstructure and this, in turn, for
its low stiffness. Nonetheless, the singular volumetric composition of this
tissue may also play a key role in its mechanical properties. The volumetric
composition of woven tissue extracted from the bone transport callus of sheep was
investigated and compared with that of the lamellar tissue extracted from the
cortical shell of the same bone. Significant differences were found in the
mineral and water contents, but they can be due to the different ages of both
tissues, which affects the mineral/water ratio. However, the content in organic
phase remains more or less constant throughout the mineralization process and has
proven to be a good variable to measure the different composition of both
tissues, being that content significantly higher in woven tissue. This may be
linked to the abnormally high concentration of osteocytes in this tissue, which
is likely a consequence of the more abundant presence of osteoblasts secreting
osteoid and burying other osteoblasts, which then differentiate into osteocytes.
This would explain the high formation rate of woven tissue, useful to recover the
short-term stability of the bone. Nonetheless, the more abundant presence of
organic phase prevents the woven tissue from reaching a stiffness similar to that
of lamellar tissue in the long term, when it is fully mineralized.
PMID- 29962327
TI - Additively manufactured implant components for imaging validation studies.
AB - Radiographic imaging is the current standard for evaluating postoperative joint
replacements. Prior to application, such imaging methods need to be validated to
determine the lower limits of performance under ideal conditions, using either a
phantom or cadaver setup. Conventionally manufactured orthopedic implants for use
in such studies are not always accessible and may be cost-prohibitive to
purchase. We propose the use of additively manufactured implants as a cheaper,
more accessible alternative for use in radiographic imaging validation studies.
Bias and repeatability were compared between conventionally manufactured and
additively manufactured reverse total shoulder implant sets under a standard
model-based radiostereometric analysis phantom study environment. Measurements
were compared using the humeral stem or glenosphere model relative to reference
bone beads, and the humeral stem relative to the glenosphere model to measure
implant relative displacement. Compared to the conventionally manufactured
implants, the additively manufactured implants had less bias along the internal
external rotation axis (p < 0.001), but greater bias along the abduction
adduction and flexion-extension rotation axes (p = 0.005, 0.011). Additively
manufactured implants had greater repeatability along the internal-external
rotation axis (p < 0.001), but worse repeatability along the medial-lateral
translation axis (p = 0.001) and the abduction-adduction rotation axis (p <
0.001). Differences were on the orders of 0.01 mm and 0.5 degrees . For the
purpose of validating two-dimensional-three-dimensional radiographic imaging
techniques of orthopedic implants, additively manufactured implants can be used
in place of conventionally manufactured implants, assuming they are fabricated to
the manufacturer's specifications. Observed differences were within the errors of
the measurement technique and not clinically meaningful.
PMID- 29962328
TI - Effects of Single-Walled Carbon Nanotube on the Conformation of Human Hepcidin:
Molecular Dynamics Simulation and Binding Free Energy Calculations.
AB - Non-covalent interactions of blood peptides such as Hepcidin20 and Hepcidin25
with carbon nanotubes (CNTs) have important biological effects in a wide range of
biological applications. The forces that manage the thermodynamics of interaction
between peptides and carbon nanotubes are identified through the analysis of the
interaction between CNTs and peptides. The main driving force of the interactions
is the non-bonding van der Waals' force of attractions. In addition, we
investigated the effects of different parameters in order to evaluate how the
nanotube affects the structure and stability of peptides. We indicate that the
peptide-SWCNT interactions through free energy calculations are thermodynamically
favorable. Van der Waals contribution to the interactions in Hepcidin20-SWCNT and
Hepcidin25-SWCNT complexes was negative (-134.750 and -115.641 kJ/mol,
respectively (, which confirmed an extremely strong non-covalent binding energy.
Results revealed that the interaction between nanotubes and the peptides could
lead to a substantial conformational change of the Hepcidin20 and 25 peptide
domains. Furthermore, the difference of parameter amounts calculated in both
peptides is related to their N-terminal, and loop regions. These results can
provide insights into peptide design strategies for future applications.
PMID- 29962329
TI - The Mental Health of the Organic Farmer: Psychosocial and Contextual Actors.
AB - Despite the large body of research and literature on the health and mental health
of farmers, we should not assume that research findings necessarily apply to the
organic farmer. The limited literature on the mental health of the organic farmer
points to potential differences. Research has found that workers on organic farms
may be happier than their counterparts; others have identified added sources of
stress related to the perceived need of organic farmers to embrace concepts
linked to the organic movement. However, further research is needed to identify
both risk and protective factors for mental health among organic farmers. The
purpose of this qualitative descriptive study was to explore the psychosocial and
contextual factors that may relate to the mental health of the organic farmer.
Key informant interviews were conducted with 10 farm producers and 20 farm
workers. The findings indicated that respondents recognized mental health as
influential in the workplace and the future of organic practices (e.g., the
mental, financial, physical stress). Some of the risk factors mentioned by
participants reflected those experienced by conventional, nonorganic farmers.
Participants also reported contentment with farming as an occupation, the
benefits of being connected to the land, feelings of social and environmental
responsibility, and engagement in social activities that may promote human and
social capital. These feelings and activities ultimately benefit the farmer,
contribute to social cohesion, and may have positive implications for mental
health. Results suggest that there may be protective mental health factors unique
to the organic farmer.
PMID- 29962330
TI - Analytical Advances in Clinical and Forensic Toxicology. Second Part.
PMID- 29962331
TI - Preface: A New Era of Nanoimmunology.
PMID- 29962332
TI - Targeted Delivery of siRNA Therapeutics using Ligand Mediated Biodegradable
Polymeric Nanocarriers.
AB - BACKGROUND: Cancer poses a major public health issue, is linked with high
mortality rates across the world, and shows a strong interplay between genetic
and environmental factors. To date, common therapeutics, including chemotherapy,
immunotherapy, and radiotherapy, have made significant contributions to cancer
treatment, although diverse obstacles for achieving the permanent "magic bullet"
cure have remained. Recently, various anticancer therapeutic agents designed to
overcome the limitations of these conventional cancer treatments have received
considerable attention. One of these promising and novel agents is the siRNA
delivery system; however, poor cellular uptake and altered siRNA stability in
physiological environments have limited its use in clinical trials. Therefore,
developing the ideal siRNA delivery system with low cytotoxicity, improved siRNA
stability in the body's circulation, and prevention of its rapid clearance from
bodily fluids, is rapidly emerging as an innovative therapeutic strategy to
combat cancer. Moreover, active targeting using ligand moieties which bind to
over-expressed receptors on the surface of cancer cells would enhance the
therapeutic efficiency of siRNA. CONCLUSION: In this review, we provide 1) an
overview of the non-viral carrier associated with siRNA delivery for cancer
treatment, and 2) a description of the five major cancer-targeting ligands.
PMID- 29962333
TI - Contribution of the Rho-kinase to Systemic Sclerosis and Behcet's Disease.
AB - BACKGROUND: The small GTPase Rho family and its effectors, Rho-kinases (ROCK)
play essential roles in the actin cytoskeleton organization and coordinate a
broad range of cellular functions, such as inflammatory responses, cell
contractility, migration, adhesion, proliferation, and apoptosis. METHODS: The
goal of this work is to review of existing literature about systemic sclerosis
and Behcet's disease in relation to ROCK. RESULTS: There are some evidences that
ROCK expression is elevated in patients with systemic sclerosis and Behcet's
disease. Rho/ROCK gene polymorphisms have been shown to be associated with these
disorders. Endothelial function is also impaired in these autoimmune diseases.
Rho/Rho-kinase pathway might have a crutial role in endothelial, vascular, and
fibrotic pathologies. CONCLUSION: Dysregulation in the Rho/ROCK pathway may
represent a common pathogenic mechanism in multiple autoimmune disorders. Current
evidences indicate that Rho/ROCK genes might be risk factors, and can contribute
to susceptibility and development of systemic sclerosis and Behcet's disease.
These studies may also provide important insights into the future development or
use of potential novel therapeutic approaches, such as selective Rho-kinase
inhibitors, for the treatment of patients with systemic sclerosis and Behcet's
disease.
PMID- 29962334
TI - Assessment of Coronary Microcirculation During Cardiac Catheterization.
AB - Functional tests used in the catheterization laboratory have emerged as a very
important adjunctive tool to coronary angiography that can identify patients with
myocardial blood flow impairment. Fractional Flow Reserve (FFR) measurement is
highly recommended for detection of ischemia-related coronary lesion(s) when
objective evidence of vessel-related ischemia is not available. Recently, the
much simpler instantaneous wave free ratio (iFR) was proposed as an alternative
to FFR without the requirement for administration of vasodilators. More user
friendly techniques like iFR might further contribute to value-based care in
coronary interventions.
PMID- 29962335
TI - Microvasculature Recovery by Angiogenesis After Myocardial Infarction.
AB - Advances in early reperfusion therapies focused on the revascularization of the
ischemic tissues, in the last decades, lead to reduced mortality in acute
myocardial infarction (MI) patients. However, a large proportion of patients show
inadequate myocardial perfusion because of dysfunction of the microcirculation.
The high prevalence of microvascular dysfunction after reperfusion therapies and
the negative prognostic of this procedure justify the search for therapeutic
strategies that aim to restore the microvascular network. It is well known that
the size of the initial infarct, the duration of ischemia and the efficiency of
reperfusion determine myocardial tissue damage and cardiomyocyte loss after
myocardial infarction. Therefore any advancement on the mechanisms that induce
the repair process of microvascular dysfunction after reperfused MI is of great
interest. Here, we will review the different proteins and cells known to
participate in angiogenesis induction post-MI and we will also discuss the
potential pharmacological and cellular processes that promote the recovery of
microvasculature by angiogenesis stimulation after MI.
PMID- 29962336
TI - Coronary No-Reflow Phenomenon in Clinical Practice.
AB - Timely delivered coronary revascularization with no residual anatomical stenosis
does not always lead to prompt restoration of anterograde coronary flow and
complete myocardial reperfusion. This condition is known as coronary no-reflow
and is associated with major clinical adverse events and poor prognosis. The
pathophysiology of no-reflow phenomenon is still poorly understood. Proposed
mechanisms include distal microembolization of thrombus and plaque debris,
ischemic injury, endothelial dysfunction and individual susceptibility to
microvascular dysfunction/obstruction. Older age, diabetes, hypercholesterolemia,
prolonged ischemic time, hemodynamic instability, high thrombus burden, complex
angiographic lesions and multivessel disease are frequently reported to be
associated with the no-reflow phenomenon. There is no general consensus on the
correct prevention and management of no-reflow. Non-pharmacological measures such
as distal embolic protection devices and manual thrombus aspiration did not
result in improved flow or reduction of infarct size. Current preventive measures
include reduction of time from symptoms onset to reperfusion therapy, and
intracoronary administration of vasodilators such as adenosine, verapamil or
nitroprusside.
PMID- 29962337
TI - Microvascular (dys)Function in Stable Coronary Artery Disease: Cross Talk with
Epicardial Segments.
AB - Myocardial ischemia is the consequence of an unbalance between coronary flow that
can be achieved and myocardial metabolic needs. Pathological state of both
epicardial and intramyocardial vessels may be responsible for inducing ischemia.
However, revascularization decision should be based on the severity of each
epicardial lesion that is evaluated. There are different diagnostic tools that
may help for the evaluation of each compartment which is based on the measurement
of coronary hemodynamics. Pressure-derived indices are recommended by current
guidelines for evaluation of epicardial stenosis significance. We assess the
complex interaction between hemodynamic parameters in order to understand how
different parameters are influenced in the settings of microvascular dysfunction.
PMID- 29962338
TI - Assessment of Coronary Microcirculation with Myocardial Contrast
Echocardiography.
AB - Myocardial contrast echocardiography has been used in clinical arena and for
scientific research extensively in the last fifteen years. This non-invasive, bed
side and radiation free imaging technique offers several important possibilities:
better delineation of the endocardial border, more reliable assessment of the
left ventricular wall motion abnormalities, both in rest and during stress, and
myocardial perfusion evaluation. Here we provide an overview on different
applications of the myocardial contrast echocardiography in the ischemic heart
disease with the special focus on perfusion studies and evaluation of coronary
microcirculation.
PMID- 29962339
TI - Thiazide Therapy in Chronic Kidney Disease: Renal and Extra Renal Targets.
AB - BACKGROUND: Thiazides are the most commonly used medications for the treatment of
mild and moderate hypertension. Despite their recognized effect, the mechanism by
which thiazides reduce systemic blood pressure remains uncertain. The prevailing
belief is that thiazides reduce blood pressure primarily via enhancement of salt
excretion consequent to the inhibition of the Na-Cl Cotransporter (NCC) in the
Distal Convoluted Tubules (DCT). However, recent reports point to a reduction in
peripheral vascular resistance as a major mechanism of antihypertensive effect of
thiazides. It is plausible that both mechanisms, renal and extra-renal, may be
operating simultaneously. Recent studies point to compensatory mechanisms in the
kidney distal nephron that may play a role in blunting the diuretic effect of
thiazides. Not much information is available about the efficacy of thiazides in
controlling blood pressure in individuals with Chronic Kidney Disease (CKD).
OBJECTIVE: This review will discuss the latest updates on the use and efficacy of
thiazides derivatives as diuretics and antihypertensive medications in CKD
patients. CONCLUSION: Thiazides remain effective as diuretics and
antihypertensive agents in individuals with low GFR.
PMID- 29962340
TI - Optimization of Drugs Pharmacotherapy During Pregnancy Using Physiologically
Based Pharmacokinetic Models - An Update.
AB - BACKGROUND: Clinical studies during pregnancy are rare due to ethical and
practical limitations. Giving pregnant females the same dosing regimen used in
adult males or nonpregnant females is inappropriate. Pregnancy physiologically
based pharmacokinetic modeling is a powerful tool that can be used to refine
pharmacotherapy during pregnancy. OBJECTIVE: This work provides a review of the
current status of application of physiologically based pharmacokinetic models in
developing dosing regimens in pregnant women. METHODS: A structured search was
done on Scholar Google, Science Direct and PubMed. The articles searched were
those providing physiological, anatomical and biochemical data needed for
pregnancy physiologically-based pharmacokinetic models or utilizing these models
to evaluate the effect of pregnancy on drugs pharmacokinetics. Key words used for
search include: PBPK and pregnancy, pharmacokinetic during pregnancy, ethics of
pregnancy studies. The found articles were evaluated in terms of main
pharmacokinetic features of the drug that were affected by pregnancy, the
structure of the model, the software platform used and quality of predicted
maternal and fetal exposure. RESULTS: Pregnancy physiologically-based
pharmacokinetic models can be used to optimize effective and safe dosing regimens
needed during pregnancy. Different model structures have been successfully used
for this purpose using different modeling software. CONCLUSION: More work is
needed to fill the gaps in knowledge needed to more accurately and
mechanistically simulate simultaneous exposure of the pregnant mother and her
fetus/ embryo to drugs using pregnancy physiologicallybased pharmacokinetic
modeling approach.
PMID- 29962341
TI - Development of thiazole-5-carboxylate derivatives as selective inhibition of
monoacylglycerol lipase as a target in Cancer.
AB - The signalling function of 2-arachidonoylglycerol (2-AG) in endocannabinoid
system is delineated by Monoacylglycerol lipase (MAGL). MAGL readdresses the
lipid stores in the direction of pro-tumorigenic signalling lipids in cancer
cells. Selective as well as potent MAGL inhibitors are limited in number hence
their continuous development may lead to a breakthrough invention in the field of
MAGL inhibitors. In succession of the above, we have synthesised 2-amino-4
methylthiazole-5-carboxylate derivatives and characterized them by collective use
of IR, 1H-NMR, 13C-NMR, Mass spectral data and elemental analysis. Thirteen
compounds (3c-g, 4c, 4e, 4f and 6b-f) inhibited MAGL with IC50 value 0.037-9.60
uM. Two compounds (3g and 4c) were found most potent with IC50 value 0.037 and
0.063uM respectively. Thirty synthesised compounds were sent to NCI for
anticancer screening, out of which nine compounds were selected for one dose
anticancer assay. Compounds 3g(NSC:788170) and 4c(NSC:788176)were found to be
most potent during one dose anticancer screening and fulfilled the specified
threshold for growth inhibition criteria of NCI and were further selected for
full panel five dose assay at 10-fold dilutions of five different concentrations.
The compound 3g displayed GI50 value 0.865 uM against EKVX (Non-Small Cell Lung
Cancer cell line), and 1.20 uM against MDA-MB-468(Breast Cancer cell Line), while
(4c) showed GI50 value 0.34 and 0.96 uM against HOP-92 and EKVX (Non-Small Cell
Lung Cancer cell line) and 1.08 uM against MDA-MB-231/ATCC (Breast Cancer cell
Line). In addition, molecular docking studies of the said MAGL inhibitors have
also been presented in this article.
PMID- 29962342
TI - Association Between Atrophy of the Caudate Nuclei, Global Brain Atrophy, Cerebral
Small Vessel Disease and Mild Parkinsonian Signs in Neurologically and
Cognitively Healthy Subjects Aged 45-84 Years: A Crosssectional Study.
AB - BACKGROUND: Mild Parkinsonian signs (MPS) are commonly seen in aging, and have
been related to cerebral Small Vessel Diseases (SVD) with no univocal results.
OBJECTIVE: The aim of this study was to investigate the cross-sectional relation
between MPS and White Matter Hyperintensities (WMH), lacunes, caudate atrophy,
and global cerebral atrophy in a large cohort of Neurologically and Cognitively
Healthy (NCH) aging individuals. METHOD: 1,219 NCH individuals were included in
the analysis, and underwent standard brain MRI. The items of the motor section of
the Unified Parkinson's Disease Rating Scale were used to evaluate tremor,
rigidity, bradykinesia, and gait/balance/axial dysfunction. Caudate atrophy and
global cerebral atrophy were assessed through the bicaudate ratio and the lateral
ventricles to brain ratio, respectively. WMH were assessed through two visual
rating scales. Lacunes were also rated. Associations of MPS with vascular risk
factors/diseases and imaging findings were determined through the logistic
regression analysis. RESULTS: Frontal and basal ganglia lacunes, frontal WMH,
caudate atrophy, and global cerebral atrophy were associated with bradykinesia.
Basal ganglia lacunes, caudate atrophy, and global cerebral atrophy were
associated with gait/balance/axial dysfunction. Rigidity was associated with
frontal WMH, and tremor with caudate atrophy and global cerebral atrophy. NCH
subjects with MPS, performed less than subjects without MPS in tests evaluating
global cognition and language. CONCLUSION: This study demonstrates that in NCH
aging individuals, MPS are associated with cortical and subcortical vascular and
atrophic changes, and are probably, a warning sign of incipient cognitive
decline. Subjects with MPS should manage rigorously cerebral SVD to prevent
future physical and cognitive disabilities.
PMID- 29962343
TI - Ecological Momentary Assessments and Interventions in Alzheimer's Caregiving.
AB - BACKGROUND: Caregivers of persons with Alzheimer's Disease (AD) often experience
feelings of lack of support and information from specialists when operating in
real scenarios, inclusive of old-age psychiatric wards, care homes, community,
and patient's home. OBJECTIVE: AD caregivers can provide narrative about what
issues need to be addressed in Ecological Momentary Assessment (EMA) to capture
real-time and real-scenario needs in AD caregiving, and Ecological Momentary
Interventions (EMI) as online e-learning to assist in areas of concerns. METHOD:
Twelve focus group discussions took place with AD caregivers for a total of 62
people interviewed. Once major themes in surveys and learning were identified by
using discourse analysis, AD caregivers expressed the likelihood that these
themes (where 0 meant "nil" and 1 meant "completely") would address their focal
needs in caregiving and topics in learning. Z scores for proportions and Cohen's
d effect size were calculated for each item reporting the averaged scores.
RESULTS: AD caregivers indicated that the major areas of concern that could
benefit from an EMA/EMI online platform were: support (d=3.08), collaboration
(d=1.85), medication review (d=1.21), dealing with grief and mourning, and time
(d=0.97). Moreover, they identified personal resources available to provide help
to colleagues: support (d=1.34), information (d=0.97), collaboration (d=2.06),
hospital admission (d=3.08), and hospital discharge (d=5.50). CONCLUSION: Focus
groups and narratives can be the initial stage in creating a dedicated AD app
supporting EMA/EMI in AD care.
PMID- 29962345
TI - Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic
Mice via Inhibiting beta/gamma-Secretases Activity and Enhancing alpha
Secretases.
AB - BACKGROUND: Berberine (BBR) has neuroprotective effects on many brain diseases,
including Alzheimer's disease (AD). Amyloid -beta (Abeta) senile plaque is the
most classical pathological hallmarks of AD. Abeta produces from a sequential
cleavage by beta-secretase (beta-site amyloid precursor protein cleaving enzyme
1, BACE1) and gamma -secretase. The aim of our work was to investigate whether
the neuroprotective effects of BBR on AD is related to inhibiting Abeta
pathology. METHOD: The cognitive function of mice was assessed by the Morris
water maze (MWM) test. The Abeta levels were determined by enzyme linked
immunosorbent assay; the expression of APP, sAPPalpha, ADAM10 and ADAM17,
sAPPbeta and BACE1 was detected by Western blotting; and the activity of gamma
secretase complex (NCT, PS1, Aph-1alpha and Pen-2) was determined by Western
blotting and immunohistochemistry. RESULTS: BBR improved learning and memory
deficits of APP/PS1 mice. BBR decreased Abeta levels in the hippocampus of
APP/PS1 mice. BACE1 and sAPP -beta levels in the BBR-treated groups were
significantly reduced in the hippocampus of AD mice. BBR markedly decreased the
expression of PS1, Aph-1alpha and Pen-2, but had no effect on NCT. The levels of
sAPPalpha, ADAM10 and ADAM17 in the hippocampus of BBR-treated mice significantly
increased, compared with the control ones (P<0.05). CONCLUSION: BBR inhibits the
activity of beta/gamma-secretases, enhances alpha-secretases, and lowers the
Abeta level in the hippocampus of AD mice, and improves Alzheimer's-like
cognitive impairment.
PMID- 29962346
TI - Modulation of the Cannabinoid System: A New Perspective for the Treatment of the
Alzheimer's Disease.
AB - BACKGROUND: The pathogenesis of Alzheimer's disease (AD) is somewhat complex and
has yet to be fully understood. As the effectiveness of the therapy currently
available for AD has proved to be limited, the need for new drugs has become
increasingly urgent. The modulation of the endogenous cannabinoid system (ECBS)
is one of the potential therapeutic approaches that is attracting a growing
amount of interest. The ECBS consists of endogenous compounds and receptors. The
receptors CB1 and CB2 have already been well characterized: CB1 receptors, which
are abundant in the brain, particularly in the hippocampus, basal ganglia and
cerebellum, regulate memory function and cognition. It has been suggested that
the activation of CB1 receptors reduces intracellular Ca concentrations, inhibits
glutamate release and enhances neurotrophin expression and neurogenesis. CB2
receptors are expressed, though to a lesser extent, in the central nervous
system, particularly in microglia and in immune system cells involved in the
release of cytokines. CB2 receptors have been shown to be upregulated in neuritic
plaque-associated migroglia in the hippocampus and entorhinal cortex of patients,
which suggests that these receptors play a role in the inflammatory pathology of
AD. The role of the ECBS in AD is supported by cellular and animal models. By
contrast, few clinical studies designed to investigate therapies aimed at
reducing behaviour disturbances, especially night-time agitation, eating
behaviour and aggressiveness, have yielded positive results. In this review, we
will describe how the manipulation of the ECBS offers a potential approach to the
treatment of AD.
PMID- 29962344
TI - Impact of the Presence of Select Cardiovascular Risk Factors on Cognitive Changes
among Dementia Subtypes.
AB - BACKGROUND: Studies have shown select associations between cardiovascular risk
factors and dementia, but mostly focused on Alzheimer's Disease (AD). OBJECTIVE:
We enhance these works by evaluating the relationship between the presence of
cardiovascular risk factors and the rate of cognitive decline, measured using the
Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Sum of Boxes
(CDR-SUM) on four common dementia subtypes (AD, dementia with Lewy bodies (DLB),
frontotemporal dementia (FTD), and vascular dementia (VaD), as well as non
demented elderly individuals (normal)). METHOD: We used generalized linear mixed
models with random intercepts to account for correlation at the patient and
center levels for each dementia subtype adjusting for time since initial visit,
baseline cognitive score, age, and demographic factors. The cardiovascular risk
factors evaluated included body mass index, diabetes, years of smoking, atrial
fibrillation, hypertension, and hypercholesterolemia. RESULTS: Patients diagnosed
with AD (n=1899), DLB (n=65), FTD (n=168), or VaD (n=13); or lacked cognitive
impairment (normal) (n=3583) were evaluated using data from the National
Alzheimer's Coordinating Centers. Cardiovascular risk factors were associated
with select dementia subtypes including AD and FTD. Using MMSE and CDR-SUM,
recent or active hypertension and hypercholesterolemia were associated with a
slower cognitive decline for AD patients, while higher body mass index and years
of smoking were associated with a slower cognitive decline for FTD patients.
However, several cardiovascular factors demonstrated associations with more rapid
cognitive decline. CONCLUSION: These results demonstrate disease specific
associations and can provide clinicians guidance on predicted cognitive changes
at the group level using information about cardiovascular risk factors.
PMID- 29962347
TI - OralAcute and Repeated-Doses Toxicity Study of Valepotriates from Valeriana
glechomifolia (Meyer) in Mice.
AB - Species of Valeriana show sedative, hypnotic, anxiolytic, antidepressant and anti
inflammatory properties, which are associated with valepotriates. However, data
about toxicity and safety of these compounds are still limited. The aim of this
study was to investigate the toxicity of a valepotriate-enriched fraction (VAL)
from Valeriana glechomifolia Meyer based on the Organization for Economic
Cooperation and Development (OECD) guidelines 423 and 407. In the acute study,
CF1 mice were treated with a single dose of VAL (2000 mg/kg, p.o.) and observed
for 14 days. In the repeated dose study, CF1 mice received single daily doses of
VAL (30, 150 or 300 mg/kg, p.o.) or vehicle for 28 days. These doses were chosen
based on previous results by our group and according to Guideline 407- OECD.
Acute study allowed to classify VAL in the hazard category 5. Repeat-dose study
has shown that VAL 300 mg/kg delayed weight gain and reduced food consumption in
the first week, probably due to transient sedative effects. The other doses had
no effect on animals' ponderal evolution. At the end of the treatment, all groups
had equal body weight and food consumption. None of doses altered any behavioral,
urinary, biochemical, hematological, anatomic or histological parameters. In
conclusion, a valepotriate-enriched fraction from Valeriana glechomifolia
presents relative low oral acute toxicity and does not induce evident toxicity
after oral repeated treatment (at least up to 300 mg/kg) in mice.
PMID- 29962348
TI - Reactive Oxygen Species as Intracellular Signaling Molecules in the
Cardiovascular System.
AB - BACKGROUND: Redox signaling plays an important role in the lives of cells. This
signaling not only becomes apparent in pathologies but is also thought to be
involved in maintaining physiological homeostasis. Reactive Oxygen Species (ROS)
can activate protein kinases: CaMKII, PKG, PKA, ERK, PI3K, Akt, PKC, PDK, JNK,
p38. It is unclear whether it is a direct interaction of ROS with these kinases
or whether their activation is a consequence of inhibition of phosphatases. ROS
have a biphasic effect on the transport of Ca2+ in the cell: on one hand, they
activate the sarcoplasmic reticulum Ca2+-ATPase, which can reduce the level of
Ca2+ in the cell, and on the other hand, they can inactivate Ca2+-ATPase of the
plasma membrane and open the cation channels TRPM2, which promote Ca2+-loading
and subsequent apoptosis. ROS inhibit the enzyme PHD2, which leads to the
stabilization of HIF-alpha and the formation of the active transcription factor
HIF. CONCLUSION: Activation of STAT3 and STAT5, induced by cytokines or growth
factors, may include activation of NADPH oxidase and enhancement of ROS
production. Normal physiological production of ROS under the action of cytokines
activates the JAK/STAT while excessive ROS production leads to their inhibition.
ROS cause the activation of the transcription factor NF-kappaB. Physiological
levels of ROS control cell proliferation and angiogenesis. ROS signaling is also
involved in beneficial adaptations to survive ischemia and hypoxia, while further
increases in ROS can trigger programmed cell death by the mechanism of apoptosis
or autophagy. ROS formation in the myocardium can be reduced by moderate
exercise.
PMID- 29962349
TI - A Review on Possible Therapeutic Effect of Nigella sativa and Thymoquinone in
Neurodegenerative Diseases.
AB - BACKGROUND & OBJECTIVE: Medicinal plants have attracted great attention in the
recent years and is increasingly applied instead of the chemical drugs. Several
documents showed that herbal medicine traditionally and clinically applied in the
cure and prevention of several diseases. In the recent years, different medicinal
plants and their main components have been chosen in neurological therapy. The
less toxic effects, availability, and lower price of medicinal plants versus
synthetic substances make them as excellent and simple selection in the treatment
of nervous diseases. Nigella sativa (N. Sativa) L. (Ranunculaceae), well
recognized as black cumin, has been utilized as a medicinal plant that has a
strong traditional background. Thymoquinone (TQ) is one of the main active
components of the volatile oil of N. sativa seeds and most effects and actions of
N. Sativa are mainly related to TQ. The several pharmacological properties of N.
sativa and TQ have been found, for example; anti-tumor, anti-microbial, anti
histaminic, immunomodulatory, anti-inflammatory, and anti-oxidant effects. Many
reviews have investigated this valuable plant and its components, but none of
them focused on their neuroprotective effects. Therefore, the aim of the present
review was to show comprehensive and neuropharmacological properties of N. sativa
and TQ. In this review, various studies on scientific databases regarding the
effects of N. sativa and TQ in neurological diseases have been introduced.
Studies on the neuroprotective effects of N. sativa and TQ which were published
between1979 and 2018, were searched using various databases. The results of these
studies showed that N. sativa and TQ have the protective effects against
neurodegenerative diseases, including; Alzheimer, depression, encephalomyelitis,
epilepsy, ischemia, Parkinson, and traumatic brain injury have been discussed in
the cell lines and experimental animal models. Although there are many studies
indicating the beneficial actions of this plant in the nervous system, the number
of research projects relating to the human reports is rare. CONCLUSION:
Therefore, better designed clinical trials in humans are needed to confirm these
effects.
PMID- 29962350
TI - Cardiovascular Effects Mediated by Imidazoline Drugs: an Update.
AB - Clonidine is a centrally acting antihypertensive drug. Hypotensive effect of
clonidine is mediated mainly by central a2-adrenoceptors and/or imidazoline
receptors located in a complex network of the brainstem. Unfortunately, clonidine
produces side effects such as sedation, mouth dry, and depression. Moxonidine and
rilmenidine, compounds of the second generation of imidazoline drugs, with fewer
side effects, display a higher affinity for the imidazoline receptors compared
with a2-adrenoceptors. The antihypertensive action of these drugs is due to
inhibition of the sympathetic outflow primarily through central I1-imidazoline
receptors in the RVLM, although others anatomical sites and mechanisms/receptors
are involved. Agmatine is regarded as the endogenous ligand for imidazoline
receptors. This amine modulates the cardiovascular function. Indeed, when is
administered in the RVLM mimic the hypotension of clonidine. Recent findings have
shown that imidazoline drugs also exerts biological response directly on the
cardiovascular tissues, which can contribute to their antihypertensive response.
Currently, new imidazoline receptors ligands are in development. In the present
review, we provide a brief update on the cardiovascular effects of clonidine,
moxonidine, rilmenidine, and the novel imidazoline agents since representing an
important therapeutic target for some cardiovascular diseases.
PMID- 29962351
TI - Successful Treatment for Severe Thyroid-associated Ophthalmopathy with
Tocilizumab.
AB - BACKGROUND AND OBJECTIVE: Thyroid-associated ophthalmopathy (TAO) is the most
common extrathyroidal manifestation of Graves disease, occasionally severe and
refractory to treatment, mainly in long-term disease. In these cases, one of the
most important infiltrating cytokines in the orbital tissue is interleukin-6 (IL
6). METHODS: This is a case report, the methodology consisted of the application
of tocilizumab in a patient with graves disease and the patient's follow-up.
RESULTS: We present the case of a 54-year-old male with TAO who responded
adequately to treatment with tocilizumab, an antibody directed against the IL-6
receptor. CONCLUSION: Tocilizumab could be an optional treatment in patients with
TAO.
PMID- 29962352
TI - Role of exercise on S-Klotho protein regulation: a systematic review.
AB - Humans have long sought means to extend longevity and counteract the effects of
aging on physical and mental functioning. Exercise is a highly effective way for
treating and preventing the main causes of morbidity and mortality, most of which
are associated with aging. Interestingly, the Klotho gene is involved in the
aging process. Indeed, overexpression of the Klotho gene is associated with
longevity, and experimental animals lacking this gene seem to develop multiple
disorders resembling human aging and present a shortened lifespan. Three Klotho
related genes have been identified: alpha-Klotho, beta-Klotho, and gamma-Klotho.
Exercise seems to play a key role on the secreted form of the alpha-Klotho gene
(S-Klotho) in animal models as well as in humans. We systematically reviewed the
available evidence on the associations between exercise and S-Klotho protein
regulation.
PMID- 29962353
TI - Functional Role of microRNA-23b-3p in Cancer Biology.
AB - MicroRNAs (miRNAs) constitute a class of short non coding RNAs that have crucial
biological roles by acting mainly as negative regulators of gene expression. The
alteration of miRNAs expression has been frequently demonstrated in cancer.
Furthermore, miRNAs expression data clearly revealed their possible use as
diagnostic, prognostic and predictive biomarkers. In this review, we focus on the
biological role of human miR-23b-3p in cancer. Several data demonstrated that miR
23b-3p targeted different genes involved in cancer aggressive properties such as
proliferation, migration, invasion, and metastasis. In this context, it is known
that miR-23b-3p, as other miRNAs, can target either tumor-suppressor genes or
oncogenes in different types of tumors. Therefore, its net biological effect can
be tumor-specific, mainly depending on the consequent alterations on the
downstream effects of the altered pathways. MiR-23b-3p has been found down
regulated or up-regulated in primary tumors and dysregulated in plasma and serum
of cancer patients. Its expression levels correlate with the overall survival,
disease-free survival and prognosis in several malignancies, thus assuming a
remarkable role as molecular biomarker with clinical relevance. Finally, miR-23b
3p is generally considered a responsive molecular therapeutic target as reported
in several in vitro and in vivo studies. This suggests that the ectopic
modulation of its expression may potentially be important for translational
medicine approaches.
PMID- 29962354
TI - Two Sizes May Fit All: Promoting Healthier Choices Through Regulatory Fit in Risk
Communications.
AB - AIMS AND BACKGROUND: For consumers to make healthy informed decisions (e.g.
choose a low nutritional risk food product), they need to receive and exchange
information with experts, health authorities, health and risk communicators and
other interest groups. However, communicators often face the challenge that
consumers avoid such information and have a low engagement with health and risk
communication activities. This often results from a lack of consideration of
consumers' characteristics and communications customization to them. METHODS: A
potential approach to increase engagement with communications is providing
information that fits consumers' need and goals, particularly their regulatory
orientation. We propose that such customization can be applied within a Mental
Models' Approach operationalized through a recently patented Mental Modeling
Technology PlatformTM (US9262725B2). RESULTS: Drawing results from psychological
science and particularly Regulatory Focus Theory, communications can be
customized to two global individual's goal orientation: 1) Promotion focus; 2)
Prevention Focus. Communications customized into a promotion orientation (vs.
prevention orientation) should make salient gains/positive consequences (vs.
losses/negative consequences). Regulatory orientation should be measured in
Mental Models Approach step two and message customization in step three
(communication design). CONCLUSION: The role of individual psychological factors
which influence food perception and choice should be considered in future
studies/interventions to promote healthier decisions. Those responsible for
designing mass dissemination messages and/or public health interventions, may
benefit from using regulatory fit to facilitate behavior change, particularly
when cost-effective personalized bidirectional communications are not possible.
PMID- 29962355
TI - Invited commentary in response to: Serum 25-hydroxyvitamin D, calcium and
parathyroid hormone in Native and European populations in Greenland.
PMID- 29962356
TI - A Pilot of a UK Emergency Medical Team (EMT) Medical Record During a Deployment
Training Course.
AB - : IntroductionImproving medical record keeping is a key part of the World Health
Organization's (WHO's; Geneva, Switzerland) drive to standardize and evaluate
emergency medical team (EMT) response to sudden onset disasters (SODs).ProblemIn
response to the WHO initiative, the UK EMT is redeveloping its medical record
template in line with the WHO minimum dataset (MDS) for daily reporting. When
changing a medical record, it is important to understand how well it functions
before it is implemented. METHODS: The redeveloped medical record was piloted at
a UK EMT deployment course using simulated patients in order to examine ease of
use by practitioners, and rates of data capture for key MDS variables. RESULTS:
Some parts of the form were consistently poorly filled in, and the way in which
the form was completed suggested that the flow of the form did not align with the
recorder's natural thought processes when under pressure. CONCLUSION: Piloting of
a single-sheet triplicate medical record during an EMT deployment simulation led
to significant modifications to improve data capture and function.Jafar AJN,
Fletcher RJ, Lecky F, Redmond AD. A pilot of a UK emergency medical team (EMT)
medical record during a deployment training course. Prehosp Disaster Med.
2018;33(4):441-447.
PMID- 29962357
TI - Hypotension within 1 week of life associated with poor short- and long-term
outcomes in very low birth weight infants.
AB - We examined whether hypotension in very low birth weight infants aged?1 week was
associated with hospital morbidities and overall mortality. Further, we studied
whether hypotension was associated with poor neurodevelopmental outcomes in these
patients at the corrected age of 18 months. A total of 166 very low birth weight
infants were studied during this period. Hospital outcomes and neurodevelopmental
outcomes at the corrected age of 18 months were evaluated. Among the 166 very low
birth weight infants, 95 patients (57.2%) experienced hypotension at?1 week and
were associated with an increased incidence of morbidities and mortality. At the
corrected age of 18 months, hypotension of the?1 week group had significantly
lower scores in all three - cognitive, language, and motor - composites of the
Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III)
screening tests. In addition, a multivariable logistic regression analysis showed
that longer mechanical ventilation and periventricular leukomalacia were
additionally associated with worse cognitive and language neurodevelopmental
outcomes. Hypotension in very low birth weight infants within 1 week of life was
associated with increased morbidities and overall mortality. It was also
associated with an increased risk of cognitive and language outcomes.
PMID- 29962358
TI - Gastrointestinal involvement in Kawasaki disease: a case report.
AB - Kawasaki disease is an acute febrile multisystem vasculitis. The term Incomplete
Kawasaki disease is used in the presence of a minimum of two diagnostic criteria
of clinical Kawasaki syndrome accompanied by at least 5 days of fever, the
absence of any other reasons characterising the disease, and the presence of
severe systemic inflammation findings. Gastrointestinal symptoms, notably
diarrhoea, abdominal pain, and vomiting, frequently occur, and elevated serum
aminotransferases, gallbladder hydrops, and rarely other forms of
gastrointestinal involvement such as ischaemic colitis, intussusception, hepatic
necrosis, splenic infarct, intestinal pseudo-obstruction, colitis, and colon
oedema are also reported. In this paper, we present an incomplete and atypical
Kawasaki case that explicitly shows gastrointestinal involvement. Progressive
bowel oedema was detected in the patient presenting with severe abdominal pain
and distension. We determined an aneurysm in the right coronary artery and
diffuse dilatation in the left main coronary artery despite administration of
early intravenous immunoglobulin. In addition to the cardiac problem,
hypoalbuminaemia, electrolyte imbalance, sterile pyuria, hepatosplenomegaly, and
hydrops of the gallbladder were observed in the case. All findings, including
progressive bowel oedema accompanying abdominal distension, improved markedly
after the second dose of intravenous immunoglobulin.
PMID- 29962359
TI - Personalized prediction of antidepressant v. placebo response: evidence from the
EMBARC study.
AB - BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous condition
in terms of symptom presentation and, likely, underlying pathophysiology.
Accordingly, it is possible that only certain individuals with MDD are well
suited to antidepressants. A potentially fruitful approach to parsing this
heterogeneity is to focus on promising endophenotypes of depression, such as
neuroticism, anhedonia, and cognitive control deficits. METHODS: Within an 8-week
multisite trial of sertraline v. placebo for depressed adults (n = 216), we
examined whether the combination of machine learning with a Personalized
Advantage Index (PAI) can generate individualized treatment recommendations on
the basis of endophenotype profiles coupled with clinical and demographic
characteristics. RESULTS: Five pre-treatment variables moderated treatment
response. Higher depression severity and neuroticism, older age, less impairment
in cognitive control, and being employed were each associated with better
outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross
validation, the PAI model predicted that 31% of the sample would exhibit a
clinically meaningful advantage [post-treatment Hamilton Rating Scale for
Depression (HRSD) difference ?3] with sertraline relative to placebo. Although
there were no overall outcome differences between treatment groups (d = 0.15),
those identified as optimally suited to sertraline at pre-treatment had better
week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d =
0.58). CONCLUSIONS: A subset of MDD patients optimally suited to sertraline can
be identified on the basis of pre-treatment characteristics. This model must be
tested prospectively before it can be used to inform treatment selection.
However, findings demonstrate the potential to improve individual outcomes
through algorithm-guided treatment recommendations.
PMID- 29962360
TI - What is the Optimal Age for Students to Receive Cardiopulmonary Resuscitation
Training?
AB - OBJECTIVES: Training students has been proven to be the optimal way to deliver
cardiopulmonary resuscitation (CPR) skills. However, it is somehow unknown
whether or not the current recommendations appropriate for Caucasian students are
also suitable for East Asian students. The purpose of this study is to explore
the best age for East Asian students to receive CPR training. METHODS: Students
were recruited from six schools. Students participated in a standard CPR training
program provided by tutors. Each student attended a 60-minute training session
with a manikin. After being trained, within one hour, the student's compression
quality was assessed. RESULTS: A total of 360 students who constituted 12
continuous grades were recruited for this study. Adequate compression depth and
satisfactory compression rate with correct hand position could be achieved since
the age of 12. However, successful compression rate and complete release could be
achieved since the younger age of six. CONCLUSIONS: Current recommendations for
Caucasian students to cultivate a full-capacity CPR rescuer at the age of 12 are
also appropriate for East Asian students. However, the optimal age for students
to receive CPR training should be decided based on evidence and importance
assessment of CPR.He D, Huang K, Yang Y, Jiang W, Yang N, Yang H. What is the
optimal age for students to receive cardiopulmonary resuscitation training?
Prehosp Disaster Med. 2018;33(4):394-398.
PMID- 29962361
TI - Food identification by barcode scanning in the Netherlands: a quality assessment
of labelled food product databases underlying popular nutrition applications.
AB - OBJECTIVE: The quality of labelled food product databases underlying popular diet
applications (apps) with barcode scanners was investigated. DESIGN: Product
identification rates for the scanned products and the availability and accuracy
of nutrient values were calculated. SETTING: One hundred food products were
selected from the two largest supermarket chains in the Netherlands. Using the
barcode scanners of the selected apps, the products were scanned and the results
recorded as food diary entries. The collected data were exported. SUBJECTS: Seven
diet apps with barcode scanner and food recording feature were selected from the
Google Play and Apple app stores. RESULTS: Energy values were available for 99 %
of the scanned products, of which on average 79 % deviated not more than 5 % from
the true value. MyFitnessPal provided values for sixteen nutrients, while
Virtuagym Food and Yazio provided values for only four nutrients. MyFitnessPal
also showed the largest percentage of correctly identified products (i.e. 96 %)
and SparkPeople the smallest (i.e. 5 %). The accuracy of the provided nutrient
values varied greatly between apps and nutrients. CONCLUSIONS: While energy was
the most consistently and accurately reported value, the availability and
accuracy of other values varied greatly between apps. Whereas popular diet apps
with barcode scanners might be valuable tools for dietary assessments on the
product and energy level, they appear less suitable for assessments on the
nutrient level. The presence of user-generated database entries implies that the
availability of food products might vary depending on the size and diversity of
an app's user base.
PMID- 29962362
TI - Outpatient antimicrobial stewardship targets for treatment of skin and soft
tissue infections.
AB - OBJECTIVE: We sought to identify factors associated with long duration and/or non
first-line choice of treatment for pediatric skin and soft-tissue infections
(SSTIs). DESIGN: Retrospective cohort study. SETTING: Ambulatory encounter claims
of Medicaid-insured children lacking chronic medical conditions treated for SSTI
and/or animal bite injury in Ohio in 2014. METHODS: For all diagnoses, long
treatment duration was defined as treatment >7 days. Non-first-line choice of
treatment for SSTI included treatment with 2 antimicrobials dispensed on the same
calendar day or any treatment not listed in the Infectious Diseases Society of
America guidelines. The adjusted odds of (1) long treatment duration and (2) non
first-line choice of treatment were calculated for patient age, prescriber type,
and patient county of residence characteristics (ie, rural vs metropolitan area
and poverty rate). RESULTS: Of 10,310 encounters with complete data available,
long treatment duration was prescribed in 7,968 (77.3%). The most common duration
of treatment prescribed was 10 days. A non-first-line choice was prescribed in
1,030 encounters (10%). Dispensation of 2 antimicrobials on the same calendar day
was the most common reason for the non-first-line choice, and of these,
trimethoprim-sulfamethoxazole plus a first-generation cephalosporin was the most
common regimen. Compared to pediatricians, the adjusted odds ratio of long
treatment duration was significantly lower for all other primary care
specialties. Conversely, nonpediatricians were more likely to prescribe a non
first-line treatment choice. Patient residence in a high-poverty county increased
the odds of both long duration and non-first-line choice of treatment.
CONCLUSIONS: Healthcare claims may be utilized to measure opportunities for first
line choice and/or shorter duration of treatment for SSTI.
PMID- 29962363
TI - Nonlinear Modelling for Predicting Patient Presentation Rates for Mass
Gatherings.
AB - : IntroductionMass gatherings are common in Australia. The interplay of
variables, including crowd density and behavior, weather, and the consumption of
alcohol and other drugs, can pose a unique set of challenges to attendees' well
being. On-site health services are available at most mass gatherings and reduce
the strain on community health facilities. In order to efficiently plan and
manage these services, it is important to be able to predict the number and type
of presenting problems at mass gatherings.ProblemThere is a lack of reliable
tools to predict patient presentations at mass gatherings. While a number of
factors have been identified as having an influence on attendees' health, the
exact contribution of these variables to patient load is poorly understood.
Furthermore, predicting patient load at mass gatherings is an inherently
nonlinear problem, due to the nonlinear relationships previously observed between
patient presentations and many event characteristics. METHODS: Data were
collected at 216 Australian mass gatherings and included event type, crowd
demographics, and weather. Nonlinear models were constructed using regression
trees. The full data set was used to construct each model and the model was then
used to predict the response variable for each event. Nine-fold cross validation
was used to estimate the error that may be expected when applying the model in
practice. RESULTS: The mean training errors for total patient presentations were
very high; however, the distribution of errors per event was highly skewed, with
small errors for the majority of events and a few large errors for a small number
of events with a high number of presentations. The error was five or less for 40%
of events and 15 or less for 85% of events. The median error was 6.9
presentations per event. CONCLUSION: This study built on previous research by
undertaking nonlinear modeling, which provides a more realistic representation of
the interactions between event variables. The developed models were less useful
for predicting patient presentation numbers for very large events; however, they
were generally useful for more typical, smaller scale community events. Further
research is required to confirm this conclusion and develop models suitable for
very large international events.Arbon P, Bottema M, Zeitz K, Lund A, Turris S,
Anikeeva O, Steenkamp M. Nonlinear modelling for predicting patient presentation
rates for mass gatherings. Prehosp Disaster Med. 2018;33(4):362-367.
PMID- 29962364
TI - Associations between home and school neighbourhood food environments and
adolescents' fast-food and sugar-sweetened beverage intakes: findings from the
Olympic Regeneration in East London (ORiEL) Study.
AB - OBJECTIVE: To examine associations between availability of fast-food restaurants
and convenience stores in the home and school neighbourhoods, considered
separately and together, and adolescents' fast-food and sugar-sweetened beverage
(SSB) intakes. DESIGN: Cross-sectional observational study. SETTING: East London,
UK. SUBJECTS: Adolescents (n 3089; aged 13-15 years) from the Olympic
Regeneration in East London (ORiEL) Study self-reported their weekly frequency of
fast-food and SSB consumption. We used food business addresses collected from
local authority registers to derive absolute (counts) and relative (proportions)
exposure measures to fast-food restaurants and convenience stores within 800 m
from home, school, and home and school combined. Associations between absolute
and relative measures of the food environment and fast-food and SSB intakes were
assessed using Poisson regression models with robust standard errors. RESULTS:
Absolute exposure to fast-food restaurants or convenience stores in the home,
school, or combined home and school neighbourhoods was not associated with any of
the outcomes. High SSB intake was associated with relative exposure to
convenience stores in the residential neighbourhood (risk ratio=1.45; 95 % CI
1.08, 1.96) and in the home and school neighbourhoods combined (risk ratio=1.69;
95 % CI 1.11, 2.57). CONCLUSIONS: We found no evidence of an association between
absolute exposure to fast-food restaurants and convenience stores around home and
school and adolescents' fast-food and SSB intakes. Relative exposure, which
measures the local diversity of the neighbourhood food environment, was
positively associated with SSB intake. Relative measures of the food environment
may better capture the environmental risks for poor diet than absolute measures.
PMID- 29962365
TI - Body condition, live weight and success in agonistic encounters in mixed parity
groups of sows during gestation.
AB - Group housing of gestating sows benefits their welfare by allowing them freedom
of movement and the opportunity for social interaction. However, social life
could also bring disadvantages for individuals who receive direct aggression or
are displaced from the feeder. The aim of this study was to investigate
associations between social behaviour, body condition and live weight. Gestating
sows (n=298) were investigated on a commercial farm. Sows were housed in mixed
parity groups where two single space, ad libitum trough feeders served 12
animals. Sows were weighed, body condition scored and had their back fat layer
measured at mixing, 4 weeks after insemination and again before farrowing. Social
status was estimated based on the numbers of won and lost agonistic interactions
at mixing and at the end of gestation. In addition, tear staining was scored
before the farrowing and reproductive performance data were collected. With the
aid of video recordings, 100 to 150 interactions per group were observed. Winning
percentage at mixing and at the end of gestation were associated (P<0.05) and
appeared relatively stable within individuals. Tear staining scores and litter
sizes were not associated with winning percentage at the end of gestation.
However, live weight, relative weight, body condition and back fat thickness were
associated with winning percentage (P<0.05), giving heavier animals an advantage.
Low winning percentage related to lower live weight gain, probably due to poorer
success in competition for feed. Live weight within a mixed parity group could be
used as a proxy measure for social status. Sows with low body condition score and
submissive sows might need special attention with regard to group dynamics and
housing to alleviate the effects of competition in group housing.
PMID- 29962366
TI - Effectiveness of an Assertive Community Treatment program for people with severe
schizophrenia in mainland China - a 12-month randomized controlled trial.
AB - BACKGROUND: Assertive Community Treatment (ACT) is an evidence-based treatment
program for people with severe mental illness developed in high-income countries.
We report the first randomized controlled trial of ACT in mainland China.
METHODS: Sixty outpatients with schizophrenia with severe functional impairments
or frequent hospitalizations were randomly assigned to ACT (n = 30) or standard
community treatment (n = 30). The severity of symptoms and level of social
functioning were assessed at baseline and every 3 months during the 1-year study.
The primary outcome was the duration of hospital readmission. Secondary outcomes
included a pre-post change in symptom severity, the rates of symptom relapse and
gainful employment, social and occupational functioning, and quality of life of
family caregivers. RESULTS: Based on a modified intention-to-treat analysis, the
outcomes for ACT were significantly better than those of standard community
treatment. ACT patients were less likely to be readmitted [3.3% (1/30) v. 25.0%
(7/28), Fisher's exact test p = 0.023], had a shorter mean readmission time [2.4
(13.3) v. 30.7 (66.9) days], were less likely to relapse [6.7% (2/30) v. 28.6%
(8/28), Fisher's exact test p = 0.038], and had shorter mean time in relapse [3.5
(14.6) v. 34.4 (70.6) days]. The ACT group also had significantly longer times re
employed and greater symptomatic improvement and their caregivers experienced a
greater improvement in their quality of life. CONCLUSION: Our results show that
culturally adapted ACT is both feasible and effective for individuals with severe
schizophrenia in urban China. Replication studies with larger samples and longer
duration of follow up are warranted.
PMID- 29962367
TI - Is aberrant affective cognition an endophenotype for affective disorders? - A
monozygotic twin study.
AB - BACKGROUND: Identification of endophenotypes can improve prevention, detection
and development of new treatments. We therefore investigated whether aberrant
affective cognition constitutes an endophenotype for affective disorders by being
present in monozygotic (MZ) twins with unipolar or bipolar disorder in partial
remission (i.e. affected) and their unaffected co-twins (i.e. high-risk) relative
to twins with no family history of affective disorder (i.e. low-risk). METHODS:
We conducted an assessor blind cross-sectional study from 2014 to 2017 of MZ
twins using Danish population-based registers in recruitment. Twins attended one
test session involving neurocognitive testing, clinical ratings and
questionnaires. Main outcomes were attention to and recognition of emotional
facial expressions, the memory of emotional self-referential words, emotion
regulation and coping strategies. RESULTS: Participants were 103 affected, 44
high-risk and 36 low-risk MZ twins. Groups were demographically well-balanced and
showed comparable non-affective cognitive performance. We observed no aberrant
affective cognition in affected and high-risk relative to low-risk twins.
However, high-risk twins displayed attentional avoidance of emotional faces (ps ?
0.009) and more use of task-oriented coping strategies (p = 0.01) compared with
affected twins. In contrast did affected twins show more emotion-oriented coping
than high- and low-risk twins (ps ? 0.004). CONCLUSIONS: Our findings provide no
support of aberrant affective cognition as an endophenotype for affective
disorders. High-risk twins' attentional avoidance of emotional faces and greater
use of task-oriented coping strategies may reflect compensatory mechanisms.
PMID- 29962368
TI - Effects of fructose consumption on postprandial TAG: an update on systematic
reviews with meta-analysis.
AB - The aim of this study was to re-examine the chronic effect (>7 d) of fructose
consumption on postprandial TAG, in adolescents and adults. The research was
carried out in March 2017 and used different electronic databases, such as
Medline (r) (Pubmed(r)), Embase(r) and Cochrane. The review considered clinical
trials (parallel or crossed) that evaluated the effect of fructose consumption
for a period longer than 7 d, in humans. Two investigators independently
performed data extraction. The outcome was the absolute delta of TAG
concentration in a 4-h postprandial period. The results were presented with delta
mean difference between treatments with 95 % CI. The calculations were made based
on random-effect models. Statistical heterogeneity of treatment effects between
studies was assessed by Cochrane's 'Q Test' and 'I 2' inconsistency test. The
meta-analysis of the twelve selected interventions (n 318) showed that fructose
generated larger variation (delta) of TAG concentrations during the postprandial
period, compared with other carbohydrates (mean difference: 8.02 (95 % CI 0.46,
15.58) mg/dl (0.09 (95 % CI 0.01, 0.18) mmol/l); I 2: 74 %). High heterogeneity
was generated almost exclusively by one study, and its withdrawal did not alter
the result. We concluded that chronic consumption of fructose (>7 d) has a
negative role on postprandial TAG in healthy adolescents and adults, as well as
in overweight/obese individuals, but not in diabetics.
PMID- 29962369
TI - The Great East Japan Earthquake, Tsunamis, and Fukushima Daiichi Nuclear Power
Plant Disaster: Lessons for Evidence Integration from a WADEM 2017 Presentation
and Panel Discussion.
AB - In April 2017, some of the health impacts of the 2011 Great East Japan
Earthquake, tsunamis, and resultant Fukushima Daiichi nuclear power plant
disaster (Okuma, Fukushima Prefecture, Japan) were presented at the 19th Congress
of the World Association for Disaster and Emergency Medicine (WADEM; Madison,
Wisconsin USA) in Toronto, Canada. A panel discussion was then opened by asking
audience members about their experiences in their own countries, and how they
would suggest taking steps to reach the goals of the Sendai Framework for
Disaster Risk Reduction 2015-2030. This paper summarizes the presentation and
panel discussion, with a particular focus on the common problems identified in
understanding and reducing health risks from disasters in multiple countries,
such as the ethical and practical difficulties in decision making on evacuating
vulnerable populations that arose similarly during the Fukushima nuclear disaster
in 2011 and Hurricane Ike's approach to Galveston (Texas USA) in 2008. This paper
also highlights the need for greater integration of research, for example through
increased review and collation of evidence from different disaster settings to
identify common problems and possible solutions, which was identified in this
panel session as a precursor to fulfilling the goals of the Sendai
Framework.Leppold C, Ochi S, Nomura S, Murray V. The Great East Japan Earthquake,
tsunamis, and Fukushima Daiichi nuclear power plant disaster: lessons for
evidence integration from a WADEM 2017 presentation and panel discussion. Prehosp
Disaster Med. 2018;33(4):424-427.
PMID- 29962370
TI - Investigating the efficiency of a bio-inspired insect repellent surface
structure.
AB - Most insects with smooth or hairy adhesive pads have very little problems in
attaching to smooth substrates. A careful selection of surface roughness,
however, can effectively limit the contact area of the adhesive organs with the
surface. In comparison to conventional toxin-based insect repelling methods,
biologically inspired micro- and nanostructured insect repellent surface
structures, thus, offer a great potential to effective and environmentally
friendly control insect pests. We here present a simple experimental approach to
qualitatively and quantitatively analyse the efficiency of a micro- and nanorough
surface structure. Nauphoeta cinerea and Gastrophysa viridula as model organisms
for insects with smooth and hairy adhesive pads, respectively, were placed in an
enclosed environment. The escape movements of freely running insects over either
the repellent or a control surfaces were counted and analyzed in detail. The
tested surface structures were able to significantly reduce the escape of
cockroaches with smooth adhesive pads by 44.1%. Interestingly, the data indicates
that N. cinerea might use mechanical cues from the antenna to discriminate
between surfaces before making contact with the adhesive pads. G. viridula with
hairy adhesive pads were not significantly affected by the surface structure. By
carefully adjusting 'critical' surface topography parameters relevant for insect
adhesion, more efficient and selective repellent surfaces might be achieved. Such
nanostructure-based insect repellent surfaces could also help to utilize
recruitment behavior of certain insect species and might present a novel approach
to effectively control insect pests.
PMID- 29962371
TI - Unsupervised classification of tissues composition for Monte Carlo dose
calculation.
AB - The purpose of this study is to investigate the potential of k-means clustering
to efficiently reduce the variety of materials needed in Monte Carlo (MC) dose
calculation. A numerical phantom with 31 human tissues surrounded by water is
created. K-means clustering is used to group the tissues in clusters of constant
elemental composition. Four different distance measures are used to perform the
clustering technique: Euclidean, Standardized Euclidean, Chi-Squared and
Cityblock. Dose distributions are calculated with MC simulations for both low-kV
photons and MeV protons using the clustered and reference elemental composition.
Comparison between the dose distributions in the clustered and non-clustered
phantom are made to assess the impact of clustering with each distance measure.
The statistical significance of the differences observed between the four
different metrics is determined by comparing the accuracy of energy absorption
coefficients (EAC) of low-kV photons and proton stopping powers relative to water
(SPR) for repeated clustering procedures. The performance of the proposed
approach for a larger number of original materials is evaluated similarly by
using a population of 62 000 statistically generated materials grouped into
classes defined with supervised and unsupervised classification. In the phantom
geometry, the Chi-Squared distance is the one introducing the smallest error on
dose distribution and significant differences are observed between the EAC and
SPR values predicted by each distance metric. The proposed approach is also shown
to be equivalent to a state-of-the-art supervised classification method for
proton therapy, but beneficial for low-kV photons applications. In conclusion, k
means clustering successfully reduces the variety of materials needed for
accurate MC dose calculation. Based on the performance of four distance measures,
we conclude that k-means clustering using the Chi-Squared distance introduces the
smallest errors on dose distribution. The method is shown to yield similar or
improved accuracy on key physical parameters compared to supervised
classification.
PMID- 29962372
TI - Hypothiocyanous Acid Suppresses PolyI:C-Induced Antiviral Responses by Modulating
IRF3 Phosphorylation in Human Airway Epithelial Cells.
AB - Pattern recognition receptors recognize RNA viruses and trigger type I and III
interferon (IFN) production and apoptosis to limit viral replication and spread.
Some innate immune cells produce oxidants in response to viral infection to
protect against invasion. Recent studies have demonstrated the virucidal activity
of hypothiocyanous acid (HOSCN), an oxidant generated by the peroxidase-catalyzed
reaction of thiocyanate with hydrogen peroxide. However, the effects of HOSCN on
host antiviral responses are still unknown. In this study, we aimed to clarify
the role of HOSCN in host antiviral responses against RNA viruses in airway
epithelial cells using polyinosinic-polycytidylic acid (polyI:C), a mimic of
viral RNA. Our results show that HOSCN repressed antiviral responses in NCI-H292
human airway epithelial cells. HOSCN decreased polyI:C-induced apoptosis and the
expression levels of IFNB1, IFNL1, IFNL2 and IFNL3 mRNAs. In addition, the
induction of other interferon regulatory factor 3 (IRF3)-dependent genes was also
suppressed by HOSCN. Further analyses focused on IRF3 revealed that HOSCN
inhibited the phosphorylation of IRF3 at Ser386 and Ser396 as well as its
dimerization and nuclear translocation by inhibiting the phosphorylation of TANK
binding kinase 1 (TBK1). Furthermore, HOSCN led to the phosphorylation of IRF3 at
residues other than Ser386 and Ser396, implying that HOSCN may cause a
conformational change in IRF3 to impair its function. Collectively, these results
suggest that HOSCN plays a novel signaling role in the antiviral response, acting
as a negative regulator of apoptotic and TBK1-IRF3 signaling pathways and
limiting IRF3-dependent gene expression.
PMID- 29962373
TI - Prediction of the Standard Gibbs Energy of Ion Transfer across the 1,2
Dichloroethane/Water Interface.
AB - The standard Gibbs energy of ion transfer at the 1,2-dichloroethane/water
interface (DeltaGtr degrees ,W->O) was determined for 26 organic cations and 24
anions by means of ion-transfer voltammetry with a micro oil/water interface.
Based on the data sets, a theoretical analysis was performed with the non-Bornian
solvation model, in which the solvation energy of an organic ion is evaluated
from local electric fields on the surface of the ion. The semi-empirical
equations thus obtained are available for relatively accurate prediction of
DeltaGtr degrees ,W->O for organic ions. The mean absolute error was 1.9 or 3.1
kJ mol-1 for cations or anions, respectively, corresponding to the error of ~20
or ~30 mV in the standard ion-transfer potential. In this paper, energy
decomposition has been performed to discuss different contributions to DeltaGtr
degrees ,W->O from the "hydrated" (strongly charged) and positively and
negatively charged "non-hydrated" (moderately charged) surfaces as well as from
the hydrophobic interaction (cavity formation energy).
PMID- 29962374
TI - Effects of Cholesterol Concentration and Osmolarity on the Fluidity and Membrane
Tension of Free-standing Black Lipid Membranes.
AB - Although the mechanical properties and compositions of lipid bilayer membranes
can change upon deformation, the fundamental relations between the composition,
membrane tension and fluidity of membranes with little curvature have not yet
been studied. In the current study, the membrane tension and the diffusion
coefficients of free-standing black lipid membranes (BLMs), based on 1,2-dioleoyl
sn-glycero-3-phosphocholine (DOPC), were observed by systematic control of the
cholesterol concentration and the osmotic pressure with the laser-induced surface
deformation (LISD) and fluorescence recovery after photobleaching (FRAP)
techniques. When the osmotic pressure was raised and, therefore, the curvature
became larger, both the membrane tension and the diffusion coefficients increased
as well. On the other hand, when the cholesterol concentration was raised, the
membrane tension increased whereas the diffusion coefficient decreased. The
importance of the present results goes beyond this quantitative evaluation of the
relation between the membrane tension and the fluidity, as it clarifies the
changes in the fundamental properties of lipid bilayers upon natural fluctuations
and perturbative deformation that were hitherto unknown.
PMID- 29962375
TI - Preparation of Complexes between Ovalbumin Nanoparticles and Retinoic Acid for
Efficient Induction of Tolerogenic Dendritic Cells.
AB - The induction of antigen-specific immunotolerance has been gathering attention
concerning the therapy of allergy and autoimmune diseases. Tolerogenic dendritic
cells (tDCs) play crucial roles in immunotolerance therapy because they induce
anergic responses for auto-reactive helper T cells, and also enhance
differentiation to regulatory T cells to maintain tolerance against auto
antigens. All-trans retinoic acid (ATRA) is one of the representative molecules
used to induce tDCs. We have proposed a simple formulation of ovalbumin
nanoparticles complexed with ATRA (OVA/RA NPs). OVA/RA NPs were taken up by DCs
and successfully induced phenotypes of tDCs.
PMID- 29962376
TI - Visualization of Asparaptine in Asparagus (Asparagus officinalis) Using MALDI
IMS.
AB - Asparaptine, an inhibitor of angiotensin-converting enzyme (ACE), is a newly
discovered compound in asparagus. Asparaptine is a conjugate of arginine and
asparagusic acid; this compound is suggested to be effective for preventing high
blood pressure. For this reason, asparaptine has attracted remarkable attention
in recent years, and it was therefore necessary to carry out further research. No
studies to date have investigated the localization of asparaptine in asparagus.
In this study, the localization of asparaptine in asparagus was clarified using
matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI
IMS), a powerful method to visualize molecules.
PMID- 29962377
TI - Development of a Visualization Method for Imidacloprid in Drosophila melanogaster
via Imaging Mass Spectrometry.
AB - Imidacloprid is widely used for exterminating harmful insects; however,
information regarding its distribution in insects is limited. Herein, we
developed a visualization method for imidacloprid in Drosophila melanogaster, by
using matrix-assisted laser desorption/ionization imaging mass spectrometry
(MALDI-IMS). IMS requires sample cryosections; however, certain challenges
prevail in retaining fly morphology in sections owing to their small size and
heterogeneous components. Therefore, the section preparation method was optimized
first, followed by imidacloprid distribution visualized using MALDI-IMS. Using
10% gelatin as an embedding material and 70% ethanol for pretreatment, the gaps
between embedding material and D. melanogaster body surface were reduced. The
tight adhesion between embedding media and D. melanogaster retains fly morphology
in sections. Furthermore, the imidacloprid standard was analyzed separately via
MALDI and electrospray ionization (ESI), and imidacloprid was converted to
guanidine-imidacloprid via laser irradiation. Consequently, the imidacloprid
distribution in D. melanogaster was successfully visualized using guanidine
imidacloprid as the target peak.
PMID- 29962378
TI - GLP-1 Receptor Agonist Exendin-4 Attenuates NR4A Orphan Nuclear Receptor NOR1
Expression in Vascular Smooth Muscle Cells.
AB - AIMS: Recently, incretin therapy has attracted increasing attention because of
its potential use in tissue-protective therapy. Neuron-derived orphan receptor 1
(NOR1) is a nuclear orphan receptor that regulates vascular smooth muscle cell
(VSMC) proliferation. In the present study, we investigated the vascular
protective effect of Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor
agonist, by inhibiting NOR1 expression in VSMCs. METHODS: We classified 7-week
old male 129X1/SvJ mice into control group and Ex-4 low- and high-dose-treated
groups fed normal or high-fat diets, respectively. Endothelial denudation
injuries were induced in the femoral artery at 8 weeks of age, followed by the
evaluation of neointima formation at 12 weeks of age. To evaluate VSMC
proliferation, bromodeoxyuridine incorporation assay and cell cycle distribution
analysis were performed. NOR1 and cell cycle regulators were detected using
immunohistochemistry, western blotting, quantitative reverse-transcription
polymerase chain reaction, and luciferase assays. RESULTS: Ex-4 treatment reduced
vascular injury-induced neointima formation compared with controls. In terms of
VSMCs occupying the neointima area, VSMC numbers and NOR1-expressing
proliferative cells were significantly decreased by Ex-4 in a dose-dependent
manner in both diabetic and non-diabetic mice. In vitro experiments using primary
cultured VSMCs revealed that Ex-4 attenuated NOR1 expression by reducing
extracellular signal-regulated kinase-mitogen-activated protein kinase and cAMP
responsive element-binding protein phosphorylations. Furthermore, in the cell
cycle distribution analysis, serum-induced G1-S phase entry was significantly
attenuated by Ex-4 treatment of VSMCs by inhibiting the induction of S-phase
kinase-associated protein 2. CONCLUSION: Ex-4 attenuates neointima formation
after vascular injury and VSMC proliferation possibly by inhibiting NOR1
expression.
PMID- 29962379
TI - Association between Subclinical Atherosclerosis Markers and the Level of
Accumulated Advanced Glycation End-Products in the Skin of Patients with
Diabetes.
AB - AIM: The level of accumulated advanced glycation end-products (AGEs) in the skin
has been shown to predict the risk of complications in patients with diabetes
mellitus (DM). Recently, the level of accumulated fluorescent AGEs in the skin
has become measurable as skin autofluorescence (skin AF) using a non-invasive
apparatus, autofluorescence reader. The purpose of this study was to evaluate the
association between skin AF and the subclinical atherosclerosis markers,
especially endothelial dysfunction, in patients with DM. METHODS: We enrolled 140
Japanese subjects with DM who attended Osaka University Hospital, and measured
the skin level of AGEs by skin AF and three subclinical atherosclerosis markers:
endothelial function by flow-mediated vasodilation, FMD; carotid intima-media
thickness, IMT; and brachial-ankle pulse wave velocity, baPWV. RESULTS: FMD was
significantly associated with skin AF (r=-0.259, p=0.002). Furthermore, a
stepwise multivariate regression analysis revealed that skin AF was an
independent determinant of FMD (beta=-0.180, p=0.038). Although there were
significant associations between skin AF and maximum carotid intima-media
thickness (max-IMT)(r=0.298, p<0.001) as well as baPWV (r=0.284, p= 0.001) in
univariate analysis, skin AF was not an independent determinant of either carotid
max-IMT or baPWV after adjustment for conventional cardiovascular risk factors.
Receiver-operating characteristic curve analysis revealed that skin AF can
identify the subjects whose FMD, max-IMT, and baPWV were completely within the
normal range (C-statistics, 0.73; 95% confidence interval, 0.61-0.84; p<0.001).
CONCLUSIONS: Skin AF was independently associated with FMD as an indicator of
endothelial dysfunction, and can be utilized as a screening marker of
atherosclerosis in Japanese patients with DM.
PMID- 29962380
TI - Expression of TBC1D16 Is Associated with Favorable Prognosis of Epithelial
Ovarian Cancer.
AB - Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy with
high recurrence and poor prognosis duo to the lack of effective biomarkers. TBC1
domain family member 16 (TBC1D16), a GTPase-activating protein, is involved in
regulating intracellular trafficking in tumorigenesis and metastasis. However,
the clinical significance of TBC1D16 in EOC remains unknown. In the present
study, we investigated the expression and prognostic significance of TBC1D16 in
EOC and its relationship with the expression of vascular endothelial growth
factor (VEGF). The tissue specimens included 156 histologically confirmed EOC and
30 normal ovarian tissues. The expression of TBC1D16 and VEGF was detected by
immunohistochemistry (IHC), and the immunoreactive score was calculated with
signal intensity and percentage of positive cells. IHC results showed that
TBC1D16 and VEGF were both mainly localized in cytoplasm of epithelial cells in
normal ovarian tissues and were expressed in cancer cells. Based on the
immunoreactive score, TBC1D16 expression in EOC was categorized as "high
expression," compared with normal ovarian tissues (P < 0.05). The Chi-square test
showed that high TBC1D16 expression was related to advanced pT stages (P =
0.029), but not correlated with other clinical features. Moreover, the TBC1D16
expression was significantly higher in EOC specimens with low VEGF expression (P
< 0.001). Importantly, in both univariate and multivariate survival analyses,
high expression of TBC1D16 was significantly correlated with good overall
survival (OS). In conclusion, TBC1D16 is a predictive marker for favorable
prognosis of EOC.
PMID- 29962382
TI - Ludwigia octovalvis (Jacq.) raven extract supplementation enhances muscle
glycogen content and endurance exercise performance in mice.
AB - Ludwigia octovalvis extract (LOE) is a widely used traditional Chinese herbal
medicine. To date, few studies have demonstrated the effect of LOE
supplementation on exercise performance, physical fatigue and biochemical
profile. The purpose of this study is to evaluate the potential beneficial
effects of LOE extract on fatigue and ergogenic functions following physiological
challenge. Male ICR mice from 3 groups (n=8 per group) were orally administered
LOE for 4 weeks at 0 (vehicle), 61.5 (LOE-1X) or 307.5 (LOE-5X) mg/kg/day. LOE
supplementation was able to dose-dependently increase endurance swimming time
(P<0.0001) and decrease levels of serum lactate (P=0.0022), ammonia (P<0.0001),
creatine kinase (P<0.0001), blood urea nitrogen (P<0.0001) and glucose
utilization (P<0.0001) after acute exercise challenge. The glycogen in
gastrocnemius muscle also increased with LOE treatment in a dose-dependent manner
(P<0.0001). Biochemically, AST, ALT, LDH, CK, BUN, creatinine and UA levels were
decreased with LOE treatment. Our study shows that 4-week supplementation with
LOE increases muscle glycogen content storage to enhance exercise performance and
anti-fatigue effects.
PMID- 29962381
TI - Clinical and Economic Analysis of Lipid Goal Attainments in Chinese Patients with
Acute Coronary Syndrome Who Received Post-Percutaneous Coronary Intervention.
AB - AIM: The recommended low-density lipoprotein cholesterol (LDL-C) levels of the
guideline may be appropriate for Caucasian patients but not for other ethnic
groups. METHODS: A cohort study was conducted in Hong Kong, and acute coronary
syndrome (ACS) patients who received percutaneous coronary intervention (PCI)
between 2005 and 2015 were enrolled. The primary outcomes of interest were the
total cost of care and cardiovascular-related cost during one-year follow-up. The
cost difference by lipid goal attainments was analyzed by Poisson regression with
multivariate treatment effects. The clinical outcomes achieved by lipid goal
attainments in terms of major adverse cardiovascular events were analyzed by
multivariate Cox regression. RESULTS: Among the 4638 patients, 79.50%, 48.64%,
and 36.14% attained the LDL-C goals of <2.6, <2.0, and <1.8 mmol/L for one year,
respectively. Only about 16% patients achieved the >=50% reduction from baseline.
None of these lipid goals was associated with a significant reduction in the
total cost of care. We only identified the clinical benefits associated with the
lipid goal of <2.6 mmol/L. Other more stringent lipid goals seemed to bring a
significant economic burden on cardiovascular-related cost, but their clinical
benefits were uncertain. CONCLUSIONS: Lowering LDL-C to achieve the guideline
recommended target levels for post-PCI ACS patients may lead to fewer
cardiovascular events, but it may not necessarily lead to economic benefits
within one year of follow-up.
PMID- 29962383
TI - A Novel Morphological Marker for the Analysis of Molecular Activities at the
Single-cell Level.
AB - For more than a century, hematoxylin and eosin (H&E) staining has been the de
facto standard for histological studies. Consequently, the legacy of histological
knowledge is largely based on H&E staining. Due to the recent advent of multi
photon excitation microscopy, the observation of live tissue is increasingly
being used in many research fields. Adoption of this technique has been further
accelerated by the development of genetically encoded biosensors for ions and
signaling molecules. However, H&E-based histology has not yet begun to fully
utilize in vivo imaging due to the lack of proper morphological markers. Here, we
report a genetically encoded fluorescent marker, NuCyM (Nucleus, Cytosol, and
Membrane), which is designed to recapitulate H&E staining patterns in vivo. We
generated a transgenic mouse line ubiquitously expressing NuCyM by using a ROSA26
bacterial artificial chromosome (BAC) clone. NuCyM evenly marked the plasma
membrane, cytoplasm and nucleus in most tissues, yielding H&E staining-like
images. In the NuCyM-expressing cells, cell division of a single cell was clearly
observed as five basic phases during M phase by three-dimensional imaging. We
next crossed NuCyM mice with transgenic mice expressing an ERK biosensor based on
the principle of Forster resonance energy transfer (FRET). Using NuCyM, ERK
activity in each cell could be extracted from the FRET images. To further
accelerate the image analysis, we employed machine learning-based segmentation
methods, and thereby automatically quantitated ERK activity in each cell. In
conclusion, NuCyM is a versatile cell morphological marker that enables us to
grasp histological information as with H&E staining.Key words: in vivo imaging,
histology, machine learning, molecular activity.
PMID- 29962384
TI - P-Selectin Glycoprotein Ligand-1 (PSGL-1) Expressing CD4 T Cells Contribute
Plaque Instability in Acute Coronary Syndrome.
AB - BACKGROUND: Adhesion molecules have essential roles in the development of
atherosclerosis. We investigated whether P-selectin glycoprotein ligand-1 (PSGL
1)-expressing CD4 T cells contribute to plaque instability in acute coronary
syndrome (ACS).Methods and Results:We studied the adhesion molecules on CD4 T
cells from consecutive patients with ACS treated with thrombus-aspirating device
and compared them with healthy controls (n=48 each). Blood, thrombi, and plaque
samples from the culprit coronary arteries were collected by thrombus aspiration
performed during emergency coronary artery angiography. According to flow
cytometry results, peripheral CD4 T cells from ACS patients strongly expressed
PSGL-1 and integrin beta2 (P<0.05 for both) more than those from controls;
culprit coronary arteries contained an abundance of PSGL-1+(P<0.001) but not
integrin beta2+CD4 T cells. In addition, immunohistochemical analysis of the
thrombus-aspirating device samples revealed numerous PSGL-1+CD4 T cells in
plaques from the culprit lesions. Results from the selectin-binding assay
demonstrated that activated PSGL-1+CD4 T cells from ACS patients bound to P- or E
selectin after triggering the T-cell receptor, and adhered to endothelial cells
under laminar flow conditions (P<0.05 and P<0.05, respectively), inducing their
apoptosis (P<0.01) via activated caspase-3, which correlated with PSGL-1
expression (R=0.788, P=0.021) and was suppressed by application of a PSGL-1
specific antibody (P<0.05). CONCLUSIONS: PSGL-1 contributed to cytotoxic CD4 T
cell homing to the culprit coronary artery and promoted plaque instability in
ACS.
PMID- 29962385
TI - Design Strategies for Global Clinical Trials of Endovascular Devices for Critical
Limb Ischemia (CLI) - A Joint USA-Japanese Perspective.
AB - For more than 10 years, the Harmonization by Doing (HBD) program, a joint effort
by members from academia, industry and regulators from the United States of
America (USA) and Japan, has been working to increase timely regulatory approval
for cardiovascular devices through the development of practical global clinical
trial paradigms. Consistent with this mission and in recognition of the
increasing global public health effects of critical limb ischemia (CLI), academic
and government experts from the USA and Japan have developed a basic framework of
global clinical trials for endovascular devices for CLI. Despite differences in
medical and regulatory environments and complex patient populations in both
countries, we developed a pathway for the effective design and conduct of global
CLI device studies by utilizing common study design elements such as patients'
characteristics and study endpoints, and minimizing the effect of important
clinical differences. Some of the key recommendations for conducting global CLI
device studies are: including patients on dialysis; using a composite primary
endpoint for effectiveness that includes 6-month post-procedure therapeutic
success and target vessel patency; and using a 30-day primary safety endpoint of
perioperative death and major adverse limb events. The proposed approach will be
uniquely beneficial in facilitating both the initiation and interpretation of CLI
studies and accelerating worldwide CLI device development and innovation.
PMID- 29962386
TI - Ruptured Deep Femoral Artery Aneurysm: A Case Report.
AB - A deep femoral artery (DFA) aneurysm is a very rare pathology of the vascular
system. Peripheral arterial aneurysms constitute 4.6% of all aneurysms, of which
0.13% are DFA aneurysms. In the literature, there are still few reports on this
vascular system pathology. As a result, its diagnosis and treatment remain a
serious clinical problem. This case study is of a 95-year-old patient admitted to
our Department with anemia, swelling, and lower left leg pain. Generally, open
surgery seems to be the treatment of choice for DFA aneurysms although the
possibilities of intravascular therapy require further investigation.
PMID- 29962387
TI - Future Perspectives of Surgery for Esophageal Cancer.
AB - Esophageal cancer is one of the leading causes of cancer-related death worldwide.
Surgery plays an important role in the treatment strategies for esophageal
cancer. Recent advances in surgical techniques and perioperative management have
dramatically improved the mortality rate; however, esophagectomy remains a highly
invasive procedure that can lead to severe postoperative complications. Future
advances in thoracoscopic surgery with the development of surgical endoscopy
systems such as three-dimensional (3D) imaging systems with a 4K ultra high
definition camera or two-dimensional (2D) imaging systems with an 8K camera,
which is expected to provide 3D-like visual sensation, will enable us to further
understand the microscopic anatomy of the thoracic cavity and mediastinum, and to
perform delicate surgical procedures that enable minimally invasive esophagectomy
with mediastinal lymphadenectomy. A robot-assisted thoracoscopic esophagectomy is
attractive for surgeons and may be beneficial to esophageal cancer patients.
Preoperative simulation and intraoperative real-time navigation are expected to
further help surgeons safely perform esophagectomy with lymphadenectomy.
Reduction of the lymphadenectomy field and setting of lymphadenectomy areas with
highest priority may be feasible when sentinel node (SN) navigation is
appropriately performed in cN0 early-stage esophageal cancer. These technical
advances are expected to decrease the morbidity and mortality rate of surgery for
esophageal cancer and hopefully improve oncological outcomes.
PMID- 29962388
TI - The Efficacy and Safety of the WATCHMAN Device in LAA Occlusion in Patients with
Non-Valvular Atrial Fibrillation Contraindicated to Oral Anticoagulation: A
Focused Review.
AB - The standard treatment for stroke risk patients with non-valvular atrial
fibrillation (NVAF) is the use of oral anticoagulants (OACs). However, a
substantial number of patients have relative or absolute contraindications to
OACs due to concerns of major bleeding risk and other adverse effects while using
oral anticoagulation therapy. Recently, occurrences of exclusion of the left
atrial appendage (LAA) in patients with contraindication to anticoagulation
therapy are widely expanding worldwide, causing major contentious discussions.
The LAA is the commonest place of thrombus formation; therefore, the concept of
LAA occlusion in reducing stroke and other embolic events in NVAF patients is
very important. The current understanding of the available evidence on efficacy
and safety of LAA closure (LAAC) with the Watchman device in patients
contraindicated to OACs is the major aim of this focused review. After reviewing
a significant body of literature, a world experience with no randomized trials,
it is suggested that Watchman device implantation is effective and safe in high
risk patients with NVAF contraindicated to OACs therapy.
PMID- 29962389
TI - VATS and Intrapleural Fibrinolytic Therapy for Parapneumonic Empyema.
PMID- 29962390
TI - Lung Transplantation with Controlled Donation after Circulatory Death Donors.
AB - PURPOSE: Utilization of donation after circulatory death (DCD) donors has the
potential to decrease donor shortage in lung transplantation (LTx). This study
reviews the long-term outcome of LTx from DCD donors. METHODS: We included all
consecutive DCD (Maastricht Category III) and all donations after brain death
(DBD) donor lung transplants at our Center performed between January 2012 and
February 2017. Data were analyzed comparing the two groups in regard of survival
after LTx as primary outcome. RESULTS: Median withdrawal to cardiac arrest time
was 17 min (interquartile range [IQR]: 11.5-20.5). Median cardiac arrest to cold
perfusion was 32 min (IQR: 24.5-36.5). Primary graft dysfunction (PGD) grade 3 at
T72 occurred in three recipients. Chronic lung allograft dysfunction (CLAD) led
to death in two cases. In DCD group, there was no 90-day mortality. In DCD, group
1- and 3-year survival rates were 100% and 80%. In DBD group, 1- and 3-year
survival rates were 85% and 69% (p = 0.4). CONCLUSIONS: Our report confirmed the
comparable outcome from DCD donors compared with DBD donors. Utility of DCD
donors is a safe option to overcome donor shortage.
PMID- 29962391
TI - Efficacy of 2.5-mg Prasugrel in Elderly or Low-Body-Weight Patients.
AB - BACKGROUND: Due to concern about bleeding complications, a maintenance dose of
prasugrel 2.5 mg may be used in elderly or low-body-weight patients in Japan.
There is little information, however, on the efficacy and safety of a 2.5-mg
maintenance dose of prasugrel. Methods and Results: In this single-center,
prospective, open-label, cross-over study, a total of 44 elderly (>=75 years old)
or low body-weight (<50 kg) Japanese patients >1 month after percutaneous
coronary intervention who were treated with aspirin 81-100 mg and clopidogrel 75
mg were randomized to either prasugrel 2.5 mg or 3.75 mg instead of clopidogrel
for 14 days, with a cross-over directly to the alternate treatment for another 14
days. Platelet inhibition was assessed with the VerifyNow assay (Accumetrics, San
Diego, CA, USA) at 3 time points: baseline; day 14; and day 28. P2Y12 reaction
units (PRU) <=95 was defined as low on-treatment platelet reactivity (LPR), and
PRU >=262 as high on-treatment platelet reactivity (HPR). The prevalence of LPR
was 2.2% in patients treated with clopidogrel, 2.2% in those with prasugrel 2.5
mg, and 22.7% in those with prasugrel 3.75 mg (P<0.001). Clopidogrel resulted in
the higher prevalence of HPR compared with 2.5-mg and 3.75-mg prasugrel (40.9%
vs. 18.2% vs. 6.8%, P<0.001). CONCLUSIONS: Prasugrel 2.5 mg may be more
appropriate in elderly or lower-body-weight Japanese patients.
PMID- 29962393
TI - Extensive Necrosis Due to Vasopressors in Septic Shock.
PMID- 29962392
TI - Atherosclerotic Plaque Component as a Risk Factor for Distal Embolization During
Percutaneous Coronary Intervention - Pathology of Tissue Obtained by Distal
Protection Device.
AB - BACKGROUND: Embolism during percutaneous coronary intervention (PCI) causes
microcirculation impairment. The aim of this study was to clarify the
relationship between the pathological characteristics of tissue captured by
distal protection device (DPD) and amount of tissue accumulated in DPD. Methods
and Results: A total of 671 consecutive lesions in PCI using DPD were examined.
The amount of necrotic debris, fibrous tissue, calcified particle, platelet
thrombus and organized thrombus in the DPD baskets was histologically evaluated.
The DPD tissue amount was assessed semi-quantitatively, and the relationship
between the captured DPD tissue characteristics and tissue amount was
investigated. On pathology, 40.7% of the lesions had necrotic debris, 41.4% had
fibrous tissue, and 18.0% had calcified particle. The prevalence of lesions in
patients with acute coronary syndrome (ACS) was 62.1%. Tissue amount score
distribution was as follows: score 1 (tissue invisible), 3.9%; score 2 (tissue
clinging to the basket), 52.0%; score 3 (tissue accumulated at the bottom of the
basket), 38.5%; and score 4 (tissue accumulated in more than half of the basket),
5.7%. On multivariate analysis, necrotic debris and fibrous tissue were
associated with greater tissue amount as well as clinical presentation of ACS.
CONCLUSIONS: The presence of atherosclerotic plaque component, such as necrotic
debris and fibrous tissue, might be a risk for distal embolism during PCI.
PMID- 29962394
TI - Evidence of interspecies transmission of pathogenic Leptospira between livestock
and a domestic cat dwelling in a dairy cattle farm.
AB - A domestic cat dwelling in a dairy cattle farm with haematuria was referred for a
physical examination. The examination showed no abnormalities therefore
complementary exams were performed. Leukocytosis with neutrophilia, monocytosis
and hyperproteinaemia were detected. The urine analysis showed a bacterial
infection without ultrasound findings. Serological titers to Leptospira
interrogans serovar Pomona and Autumnalis were detected. Molecular analysis
demonstrated the presence of Leptospira spp. in urine. The findings were
consistent with subclinical leptospirosis. The cattle herd had evidence of
Leptospira infection. The microbiological exams confirmed the presence of the
Leptospira spp. in urine and serum. According to the evidence presented in this
study, cats that dwell within a dairy farm could play a role in the Leptospira
infection epidemiologically. The importance of feline leptospirosis must be
evaluated with leptospirosis control in livestock.
PMID- 29962395
TI - Seasonal variation in the number of deaths in Pteropus lylei at Wat Pho Bang Khla
temple, Thailand.
AB - Flying foxes have been widely studied as they are well-known reservoirs of
infectious agents. Understanding their population dynamics might help to explain
seasonal patterns of disease prevalence, and contribute towards the conservation
of flying fox populations. Therefore, this study explored the annual variation in
the number of deaths in P. lylei. The study was conducted from 2015-2017, at a
Buddhist temple in Thailand, which is the roosting site of P. lylei. The average
total number of bat deaths in a month significantly varied between times of a
year. A peak was observed during March and May, which ranged in the period of
birthing and lactating. There were no significant differences in the average
total number of bat deaths in a month between sexes or age classes across times
of a years.
PMID- 29962396
TI - Antimicrotubule Agent-Induced Zinc Neurotoxicity.
AB - Colchicine or vincristine depolymerize microtubules, an action which blocks
neuron axonal transport. Thus, these chemicals showed selective neurotoxicity in
hippocampal neurons. However, the mechanism of neurotoxicity by these
antimicrotubule agents has remained unclear. Our previous studies have suggested
that colchicine-induced hippocampal neuron death is caused by incremental
increases in intraneuronal free zinc. We have demonstrated that zinc transporter
3 gene deletion (ZnT3-/-) reduces dentate granule cell death after colchicine
injection. This ZnT3-/--mediated reduction of dentate granule cell death was
accompanied by a decrease in the incidence of oxidative injury. Unexpectedly, we
found that ZnT3-/- mice contain a higher glutathione (GSH) level in the
hippocampal neurons than wild type mice. Thus, ZnT3-/- mice showed less neuronal
GSH depletion by colchicine injection, and thus less neuronal death. These
results suggest that the higher levels of neuronal GSH in ZnT3-/- mice result in
less dentate granule cell death after colchicine injection. In addition to
colchicine, our lab also demonstrated that a chemotherapeutic agent, pacritaxel
(Taxol), which is a microtubule stabilizing agent, depleted vesicular zinc in the
presynaptic terminals and induced a reduction of neurogenesis. Therefore, in the
present review, we discussed how antimicrotubule agent-induced neurotoxicity and
cognitive impairment is associated with zinc dyshomeostasis in the brain.
PMID- 29962397
TI - Physiological Roles of Metallothioneins in Central Nervous System Diseases.
AB - Metallothioneins (MTs) are small-molecular weight metal-binding proteins involved
in the maintenance of tissue structure, efficient metal metabolism, and metal
detoxification and have an antioxidative effect. Moreover, MTs are expressed as
four isoforms, and there are no known patterns in their localization with various
effects. According to recent studies, MTs affect central nervous system (CNS)
diseases, and many reports suggest that each isoform of MT has a protective
effect against disease. Notably, MTs are involved in regions of diseases related
to unmet medical needs, and MTs affect intractable neurological diseases, such as
amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). This
review specifically focuses on MT-related ocular diseases, cerebral ischemia,
psychological disorders, ALS, and SMA. Each of these diseases has a separate
cause, but the conditions are related to MTs. To understand the physiological
roles of MTs in CNS diseases, we reviewed the current literature on the complex
interactions between each MT, pathological conditions, and perspectives. We also
discuss current evidence on the expression and function of MTs for diagnosis and
new therapeutic strategies.
PMID- 29962398
TI - Apolipoprotein E Gene Polymorphisms Affect the Efficacy of Thiazolidinediones for
Alzheimer's Disease: A Systematic Review and Meta-Analysis.
AB - Although several studies have evaluated the efficacy of thiazolidinediones (TZD)
for the treatment of Alzheimer's disease (AD), investigation of the impact of
apolipoprotein E (ApoE) gene polymorphisms on the efficacy of TZD remains
insufficient. We investigated the impact by conducting a systematic review and
meta-analysis. MEDLINE, Cochrane Library, and Japana Centra Revuo Medicina were
searched to identify relevant studies based on eligibility criteria. Mean
differences (MD) of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS
Cog) total score with 95% confidence intervals (CI) were calculated for subgroups
stratified by ApoE genotype. To evaluate the impact of ApoE gene polymorphisms,
meta-regression analysis was also conducted to calculate the regression
coefficient (Coef) of ApoE expression status with 95% CI. Three randomized
controlled studies comparing rosiglitazone and placebo, with a total of 2381
subjects met the eligibility criteria. ApoE expression status was reported in 983
individuals (ApoE4-positive, 141; ApoE4-negative, 842). When compared to placebo,
rosiglitazone significantly decreased ADAS-Cog score in ApoE4-negative
individuals (MD, -1.37; 95% CI, -2.09 to -0.65), but significantly increased ADAS
Cog score in ApoE4-positive individuals (MD, 2.18; 95% CI, 0.52 to 3.85). The
meta-regression analysis showed a significant association between efficacy and
ApoE expression status (Coef, 3.55; 95% CI, 1.42 to 5.68). Although the present
results should be interpreted with caution because of the limited number of
studies, our findings suggest that ApoE gene polymorphisms impact the efficacy of
rosiglitazone for AD patients. This finding would provide useful information for
the development of new agents for AD.
PMID- 29962399
TI - Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after
Exposure of Two Glycosidase Inhibitors in Mice.
AB - Acarbose and voglibose are the most widely used diabetes drugs as glycosidase
inhibitors. In this study, the use of these two inhibitors significantly
increased the content of starch in large intestine, and altered the concentration
of short-chain fatty acids (SCFAs) by affecting the intestinal microbiota.
However, there are some differences in the intestinal microbiome of the two
groups of mice, mainly in bacteria such as Bacteroidaceae bacteroides and
Desulfovibrionaceae desulfovibrio. The productions of acetate and propionate in
caecum in voglibose group were significantly higher than those in acarbose group
and two kinds of glycosidase inhibitors were close in the production of butyrate
in caecum. The Tax4Fun analysis based on Kyoto Encyclopedia of Genes and Genomes
(KEGG) data indicated that different productions of acetate and propionate
between acarbose group and voglibose group may be related to 2-oxoisovalerate
dehydrogenase and pyruvate oxidase. In addition, in-vitro experiments suggested
that voglibose had less effect on epithelial cells than acarbose after direct
stimulation. According to the recent researches of SCFAs produced by intestinal
microbiota, our comparative study shown higher concentration of these beneficial
fatty acids in the lumen of voglibose-treated mice, which implied a lower level
of inflammation.
PMID- 29962400
TI - Essential and Non-essential Elements in Scalp Hair of Diabetics: Correlations
with Glycated Hemoglobin (HbA1c).
AB - Essential elements (Ca, Mg, Zn, Cu, Fe, Cr, Mn and V) and non-essential elements
(As, Cd, Hg and Pb) were measured in scalp hair samples of 45 diabetic subjects
and 59 control subjects in Japan using inductively coupled plasma mass
spectrometry. All diabetic subjects took insulin and/or antidiabetic agents, with
glycated hemoglobin (HbA1c) ranging between 6.2 and 14.4%. The levels of Zn, Cu
and Cr in the diabetic subjects (HbA1c>7) were significantly lower than those in
the control subjects (p<0.05), and these concentrations decreased significantly
with increases in HbA1c (p<0.01). The levels of Fe and Mg in the diabetic
subjects were insignificantly lower, and the concentration of Fe decreased
significantly with increases in HbA1c (p<0.05) and the concentration of Mn tended
to decrease (p<0.10). In contrast, the concentration of As tended to increase
with increases in HbA1c (p<0.10). The concentrations of other elements, such as
Ca, Mn, V, Pb, Cd and Hg, in the diabetic subjects were similar to those of
control subjects, and did not correlate with HbA1c. The average of estimated
glomerular filtration rate (eGFR) in the diabetic subjects was 77.7+/-29.7
mL/min/1.73 m2 with large variation (12.7-148 mL/min/1.73 m2), and previous study
reported the increase of urinary excretion of Zn, Cr, Mn and Mg in diabetic
subjects. The decreases of Zn, Cu, Cr, Fe and Mg concentrations in hair may
reflect increased urinary excretion of these elements due to diabetic
nephropathy.
PMID- 29962401
TI - Antibodies and Engineered Antibody Fragments against M13 Filamentous Phage to
Facilitate Phage-Display-Based Molecular Breeding.
AB - Antibodies are essential for characterizing various analytes. "Molecular
breeding" approaches enable rapid generation of antibody mutants with desirable
antigen-binding abilities. Typically, prototype antibodies are converted to
single-chain Fv fragments (scFvs), and random mutations are genetically
introduced to construct molecular libraries with a vast diversity. Improved
species therein are then isolated via phage display genotype-phenotype-connecting
systems to separate them from a large excess of nonspecific scFvs. During these
experiments, counting of phage particles is routinely performed. However, current
methods depend on the time-consuming overnight cultivation of phage-infected
bacteria on agar plates to estimate phage numbers as plaque-forming units (pfu)
or colony-forming units, the results of which fluctuate considerably.
Immunochemical systems capturing phage particles should be a more convenient and
robust alternative. We therefore generated monoclonal antibodies against M13
filamentous phage, which is commonly used for phage display, by employing
hybridoma technology. Combinatorial use of two such antibodies (Ab-M13#53 and
#71; both specific to the major coat protein pVIII) enabled development of a
sandwich enzyme-linked immunosorbent assay (ELISA) that could measure ca. 107
1010 phage pfu/mL. To construct a more convenient system, Ab-M13#71 was converted
to the scFv form and further fused with an alkaline phosphatase variant. Using
this fusion protein, the sandwich ELISA enabled rapid (within 90 min) and
reliable phage counting without reducing the sensitivity, and the results were
reasonably consistent with those of infection-based methods. The present anti
phage antibodies and scFvs might also enable visualization of individual phage
particles by combining them with sensitive fluorescent staining.
PMID- 29962402
TI - Doxorubicin Expands in Vivo Secretion of Circulating Exosome in Mice.
AB - Modulation of tumor immunity is a known factor in the antitumor activity of many
chemotherapeutic agents. Exosomes are extracellular nanometric vesicles that are
released by almost all types of cells, which includes cancer cells. These
vesicles play a crucial role in tumor immunity. Many in vitro studies have
reproduced the aggressive secretion of exosomes following treatment with
conventional anticancer drugs. Nevertheless, how chemotherapeutic agents
including nanomedicines such as Doxil(r) affect the in vivo secretion of exosomes
is yet to be elucidated. In this study, the effect of intravenous injection of
either free doxorubicin (DXR) or liposomal DXR formulation (Doxil(r)) on exosome
secretion was evaluated in BALB/c mice. Exosomes were isolated from serum by
using an ExoQuickTM kit. Free DXR treatment markedly increased serum exosome
levels in a post-injection time-dependent manner, while Doxil(r) treatment did
not. Exosomal size distribution and marker protein expressions (CD9, CD63, and
TSG101) were studied. The physical/biological characteristics of treatment
induced exosomes were comparable to those of control mice. Interestingly,
splenectomy significantly suppressed the copious exosomal secretions induced by
free DXR. Collectively, our results indicate that conventional anticancer agents
induce the secretion of circulating exosomes, presumably via stimulating immune
cells of the spleen. As far as we know, this study represents the first report
indicating that conventional chemotherapeutics may induce exosome secretion which
might, in turn, contribute partly to the antitumor effect of chemotherapeutic
agents.
PMID- 29962403
TI - Activation of GABAergic Neurons in the Nucleus Accumbens Mediates the Expression
of Cocaine-Associated Memory.
AB - Cocaine-associated environmental cues elicit craving and relapse to cocaine use
by recalling the rewarding memory of cocaine. However, the neuronal mechanisms
underlying the expression of cocaine-associated memory are not fully understood.
Here, we investigated the possible contribution of gamma-aminobutyrate
(GABA)ergic neurons in the nucleus accumbens (NAc), a key brain region associated
with the rewarding and reinforcing effects of cocaine, to the expression of
cocaine-associated memory using the conditioned place preference (CPP) paradigm
combined with designer receptors exclusively activated by designer drugs (DREADD)
technology. The inhibitory DREADD hM4Di was selectively expressed in NAc
GABAergic neurons of vesicular GABA transporter-Cre (vGAT-Cre) mice by infusing
adeno-associated virus (AAV) vectors. Ex vivo electrophysiological recordings
revealed that bath application of clozapine-N-oxide (CNO) significantly
hyperpolarized membrane potentials and reduced the number of spikes induced by
depolarizing current injections in hM4Di-positive NAc neurons. Additionally,
systemic CNO injections into cocaine-conditioned mice 30 min before posttest
session significantly reduced CPP scores compared to saline-injected mice. These
results indicate that chemogenetic inhibition of NAc GABAergic neurons attenuated
the expression of cocaine CPP, suggesting that NAc GABAergic neuronal activation
is required for the environmental context-induced expression of cocaine
associated memory.
PMID- 29962405
TI - Temporal Kinetics of Microgliosis in the Spinal Dorsal Horn after Peripheral
Nerve Injury in Rodents.
AB - Neuropathic pain, a highly debilitating chronic pain following nerve damage, is a
reflection of the aberrant functioning of a pathologically altered nervous
system. Previous studies have implicated activated microglia in the spinal dorsal
horn (SDH) as key cellular intermediaries in neuropathic pain. Microgliosis is
among the dramatic cellular alterations that occur in the SDH in models of
neuropathic pain established by peripheral nerve injury (PNI), but detailed
characterization of SDH microgliosis has yet to be realized. In the present
study, we performed a short-pulse labeling of proliferating cells with
ethynyldeoxyuridine (EdU), a marker of the cell cycle S-phase, and found that
EdU+ microglia in the SDH were rarely observed 32 h after PNI, but rapidly
increased to the peak level at 40 h post-PNI. Numerous EdU+ microglia persisted
for the next 20 h (60 h post-PNI) and decreased to the baseline on day 7. These
results demonstrate a narrow time window for rapidly inducing a proliferation
burst of SDH microglia after PNI, and these temporally restricted kinetics of
microglial proliferation may help identify the molecule that causes microglial
activation in the SDH, which is crucial for understanding and managing
neuropathic pain.
PMID- 29962404
TI - Generation of the Adenovirus Vector-Mediated CRISPR/Cpf1 System and the
Application for Primary Human Hepatocytes Prepared from Humanized Mice with
Chimeric Liver.
AB - The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
associated protein (Cas) 9 system is now widely used as a genome editing tool.
CRISPR-associated endonuclease in Prevotella and Francisella 1 (Cpf1) is a
recently discovered Cas endonuclease that is designable and highly specific with
efficiencies comparable to those of Cas9. Here we generated the adenovirus (Ad)
vector carrying an Acidaminococcus sp. Cpf1 (AsCpf1) expression cassette (Ad
AsCpf1) for the first time. Ad-AsCpf1 was applied to primary human hepatocytes
prepared from humanized mice with chimeric liver in combination with the Ad
vector expressing the guide RNA (gRNA) directed to the Adeno-associated virus
integration site 1 (AAVS1) region. The mutation rates were estimated by T7
endonuclease I assay around 12% of insertion/deletion (indel). Furthermore, the
transduced human hepatocytes were viable (ca. 60%) at two weeks post
transduction. These observations suggest that the Ad vector-mediated delivery of
the CRISPR/AsCpf1 system provides a useful tool for genome manipulation of human
hepatocytes.
PMID- 29962406
TI - Anticancer Efficacy of the Combination of Berberine and PEGylated Liposomal
Doxorubicin in Meth A Sarcoma-Bearing Mice.
AB - Berberine, the main isoquinoline alkaloid obtained from traditional plants, e.g.,
Berberis, Coptis, Coscinium spps., etc., is known to exhibit anticancer activity
in vitro and in vivo. In this study, the anticancer potential of berberine
combined with PEGylated liposomal doxorubicin (polyethylene glycol (PEG)-lip-DOX)
was investigated. At first, the effect of berberine on endothelial cells was
examined in vitro by use of human umbilical vein endothelial cells (HUVECs):
Berberine inhibited HUVEC growth with an IC50 at 24 h of about 144 ug/mL and that
at 72 h of about 29 ug/mL. In contrast, less than 50 ug/mL berberine inhibited
the vascular endothelial growth factor (VEGF) expression to some extent after a
24-h incubation, suggesting that berberine suppressed angiogenic action under the
condition of little cytotoxicity. Next, the in vivo anticancer activity of the
combination of berberine (intraperitoneally (i.p.)) and PEG-lip-DOX
(intravenously (i.v.)) was examined in Meth A sarcoma-transplanted BALB/c mice.
The results showed that either berberine or PEG-lip-DOX exhibited
antiproliferative activity against Meth A cells. Moreover, treatment with the
combination of berberine and PEG-lip-DOX suppressed the tumor growth more
strongly than that with berberine or PEG-lip-DOX alone. Based on these findings,
the combination cancer chemotherapy with berberine and PEGylated liposomal
doxorubicin may be beneficial for the treatment of cancer.
PMID- 29962407
TI - Development of a Screening System for Targeting Carriers Using Peptide-Modified
Liposomes and Tissue Sections.
AB - Liposomes have been used as targeting carriers for drug delivery systems (DDSs),
and the carriers are able to be modified with targeting ligands, such as
antibodies and peptides. To evaluate the targetability of DDS carriers modified
with a targeting ligand, culture cells expressing the targeting molecules as well
as small animals are used. Furthermore, in vitro and in vivo screening analyses
must be repeatedly performed. Therefore, it is important to establish an easy and
high-precision screening system for targeting carriers. With this aim, we focused
that whether this ex vivo system could easily support assessment of interaction
between targeting ligand and its receptor under physiological environment and
further screen the DDS carrier-modified with targeting moiety. We examined
targeting ability via in vitro, ex vivo, and in vivo analyses using integrin
alphavbeta3-targeting C16Y-L. For the in vitro analysis, the cellular uptake of
C16Y-L was higher than that of control liposomes in colon26 cells. For the ex
vivo analysis, we performed an immunohistochemical analysis using colon26 tumor
sections. C16Y-L was specifically attached to the tumor sections, as found in the
in vitro analysis. Moreover, to evaluate the ex vivo-in vivo correlation, we
examined the intratumoral localization of C16Y-L. This result showed that C16Y-L
was accumulated not only in the tumor tissue but also in the tumor vasculature
after the intravenous injection of C16Y-L, suggesting that the ex vivo peptide
modified liposomal analysis was correlated with the in vivo analysis. Thus, the
ex vivo peptide-modified liposomal analysis may be an easy and rapid screening
system with high-precision and for consideration in in vivo conditions.
PMID- 29962408
TI - Inhibition of the Amyloidogenesis of Transthyretin by Natural Products and
Synthetic Compounds.
AB - Hereditary transthyretin (TTR)-related amyloidosis is caused by mutations in the
TTR gene. The mutations destabilize the tetramer and/or monomer of TTR, and thus
the stabilization of TTR is a key strategy for the treatment of TTR-related
amyloidosis. In this review, we summarized the natural products and synthetic
compounds that have been shown to inhibit the amyloidogenesis of TTR. The
stabilizers and/or the amyloid fibril disrupters isolated from natural sources
may become lead compounds for the treatment of TTR-related amyloidosis.
PMID- 29962409
TI - Foreword.
PMID- 29962410
TI - Is Vulnerability of the Dentate Gyrus to Aging and Amyloid-beta1-42 Neurotoxicity
Linked with Modified Extracellular Zn2+ Dynamics?
AB - The basal levels of extracellular Zn2+ are in the range of low nanomolar
concentrations in the hippocampus and perhaps increase age-dependently.
Extracellular Zn2+ dynamics is critical for cognitive activity and excess influx
of extracellular Zn2+ into hippocampal neurons is a known cause of cognitive
decline. The dentate gyrus is vulnerable to aging in the hippocampus and affected
in the early stage of Alzheimer's disease (AD). The reasons remain unclear.
Neurogenesis-related apoptosis may induce non-specific neuronal depolarization by
efflux of intracellular K+ in the dentate gyrus and be markedly increased along
with aging. Extracellular Zn2+ influx into dentate granule cells via high K+
induced perforant pathway excitation leads to cognitive decline. Modified
extracellular Zn2+ dynamics in the dentate gyrus of aged rats is linked with
vulnerability to cognitive decline. Amyloid-beta1-42 (Abeta1-42) is a causative
candidate for AD pathogenesis. When Abeta1-42 concentration reaches picomolar in
the extracellular compartment in the dentate gyrus, Zn-Abeta1-42 is formed in the
extracellular compartment and rapidly taken up into dentate granule cells,
followed by Abeta1-42-induced cognitive decline that is due to Zn2+ released from
Abeta1-42, suggesting that dentate granule cells are sensitive to extracellular
Zn2+-dependent Abeta1-42 toxicity. This paper deals with proposed vulnerability
of the dentate gyrus to aging and Abeta1-42 neurotoxicity.
PMID- 29962412
TI - Assessment of root caries under wet and dry conditions using swept-source optical
coherence tomography (SS-OCT).
AB - The purpose of this study was to compare optical properties of root caries under
two observing conditions using swept-source optical coherence tomography (SS
OCT). In vitro and natural root caries were observed by SS-OCT under wet and dry
conditions, followed by confocal laser scanning microscope (CLSM) and transverse
microradiography (TMR). Signal intensity (SI), distance between SI peaks (SI
distance) and optical lesion depth were obtained from OCT. Lesion depth was
measured from CLSM; lesion depth (LDTMR) and mineral loss (ML) were obtained from
TMR. In vitro root caries under wet and dry conditions showed different OCT
images and SI patterns. Lesion depth of OCT and that of CLSM, SI-distance and
LDTMR, LDTMR and ML significantly correlated. Under dry conditions, half natural
root caries showed similar OCT images and SI patterns as in vitro root caries.
The base of demineralized dentin could be detected more clearly under dry
conditions than under wet conditions.
PMID- 29962411
TI - Fracture resistance and stress distribution of repairing endodontically treated
maxillary first premolars with severe non-carious cervical lesions.
AB - This study was to compare the influence of glass fiber post placement and crown
restoration on endodontically treated maxillary first premolars with severe NCCLs
using three-dimensional finite element analysis and fracture resistance testing.
G1, intact teeth. G2, teeth with artificial defect. G3, composite resin (CR). G4,
CR and fiber post in buccal canal (FPB). G5, CR and fiber post in palatal canal
(FPP). G6, CR and fiber posts in buccal and palatal canals (FPBP). G7, CR and
crown (C). G8, CR, FPB, C. G9, CR, FPP, C. G10, CR, FPBP, C. Teeth in G2, G3, and
G5 showed a similar stress concentration at the tip of the defect. The fracture
resistance of G2 did not differ significantly from G3 and G5 (p>0.05) but
differed significantly from that in other groups (p<0.05). The fractures in G4
were more favorable, and the difference of those in G1 from those in G7, G8, G9,
and G10 was statistically significant (p<0.05). Restoration of root-filled
maxillary premolars with severe NCCLs using fiber post in the buccal canal may be
more efficacious than other restoration methods.
PMID- 29962413
TI - Static and dynamic evaluations of the wettability of commercial vinyl
polysiloxane impression materials for artificial saliva.
AB - This study evaluated the wettability of commercial vinyl polysiloxane impression
materials by measuring contact angles on horizontal and non-horizontal surfaces
using artificial saliva. Three light bodies (Affinis [Affi], Silagum [Sila] and
Variotime [Vario-LB]) and one extra light body (Viriotime [Vario-ELB]) were
prepared with flat surfaces. Static and dynamic contact angles were measured
using the sessile drop method as a function of time. Contact angle hysteresis was
the value of advancing contact angle minus receding contact angle. The results
indicated that all materials were classified as hydrophilic materials. Vario-ELB
and Affi showed better initial wettability than the other two materials. Vario
ELB showed more hydrophilic properties and was more vulnerable to changes in the
intraoral environment compared to Affi, Sila and Vario-LB. These results suggest
that measuring the time-dependent dynamic contact angle on the inclined surface
can provide effective information regarding the wettability of impression
materials to evaluate their clinical performance.
PMID- 29962414
TI - Effects of a modified cold atmospheric plasma jet treatment on resin-dentin
bonding.
AB - The radio-frequency atmospheric-pressure glow discharge (RF-APGD) plasma is a
novel cold atmospheric plasma (CAP) source, which has low energy characteristic.
This study investigated the effect of RF-APGD plasma on the mechanical properties
of dentin collagen and resin-dentin bonding. The scanning electron microscopy
analysis was performed before and after a novel RF-APGD plasma and a conventional
CAP treatment and a tensile test was carried out for the stiffness of dentin
collagen. The microtensile resin-dentin bond strength was tested either
immediately or after a 50,000-cycle thermocycling process. Dentin collagen
maintained an intact structure after a 45-s RF-APGD plasma treatment, whereas
even a 10-s treatment with the conventional CAP collapsed the collagen scaffold.
When compared with control groups, the RF-APGD plasma treatment showed: (i) an
improved stiffness of dentin collagen; (ii) a significant improvement in the
bonding strength before/after artificial aging. Thus, RF-APGD plasma treatment
has excellent prospects as a resin-dentin bonding protocol.
PMID- 29962415
TI - Effect of occlusal groove on abutment, crown thickness, and cement-type on
fracture load of monolithic zirconia crowns.
AB - The aim of this study was to investigate the effects of occlusal form of
abutment, occlusal thickness of monolithic zirconia crowns (MZC), and cement type
on the fracture load of MZC. Abutments were prepared with 2 types of occlusal
forms: groove-type and flat-type. These were designed so that thickness at the
central fissure region of MZC was 0.3, 0.5, or 0.7 mm. Glass ionomer cement and
resin cement were used to lute MZC to their corresponding abutment. Fracture load
was determined using a universal testing machine. As a result, groove-type
abutment had lower fracture load compared to flat-type abutment; however, the
decline in strength was smaller when resin cement was used. Additionally,
specimens with larger occlusal thickness had greater fracture load regardless of
groove or cement-type. The fracture of MZC occurred on the central fissure region
of MZC except for 0.7 mm groove-type MZC luted with resin cement.
PMID- 29962416
TI - Guided bone regeneration using a hydrophilic membrane made of unsintered
hydroxyapatite and poly(L-lactic acid) in a rat bone-defect model.
AB - The effectiveness of a previously developed unsintered hydroxyapatite (uHA) and
poly(L-lactic acid) (PLLA) hydrophilic membrane as a resorbable barrier for
guided bone regeneration (GBR) was evaluated. Critical-size 8-mm diameter bone
defects were surgically generated in the parietal bones of 24 12-week-old male
Wistar rats, which were then divided into three groups in which either a uHA/PLLA
or a collagen membrane or no membrane (control) was placed onto the bone defect.
Following sacrifice of the animals 2 or 4 weeks after surgery, bone defects were
examined using microcomputed tomography and histological analysis. Bone mineral
density, bone mineral content, and relative bone growth area values 2 or 4 weeks
after surgery were highest in the uHA/PLLA group. Four weeks after surgery, the
relative bone growth area in the uHA/PLLA group was larger than that in the
collagen group. The resorbable uHA/PLLA membrane is thus potentially effective
for GBR.
PMID- 29962418
TI - Treatment of Gingival Fenestration with Connective Tissue Graft: A Case Report.
AB - Here, we report a case of gingival fenestration requiring periodontal plastic
surgery. The patient was a 32-year-old man presenting with the chief complaint of
esthetic impairment and gingival twitching due to gingival fenestration. Baseline
examination revealed localized periodontal breakdown, including gingival
fenestration in the lower right central incisor (#41). Periodontal examination
revealed 3% of sites with a probing depth of >=4 mm and 8.9% with bleeding on
probing. Radiographic examination revealed vertical bone loss in #15 and 36,
together with buccal fenestration in #41. Based on a clinical diagnosis of
chronic periodontitis with gingival fenestration, initial periodontal therapy
comprised plaque control and scaling and root planing. Following suppression of
inflammation, occlusal adjustment was performed in the anterior teeth. As plastic
surgery, combined use of an elevated flap and a connective tissue graft was
applied at #41. Following reevaluation, the patient was placed on maintenance
care. The patient's periodontal condition has remained stable over a 6-month
period.
PMID- 29962417
TI - Renal-limited Cryoglobulinemic Vasculitis: Two Case Reports.
AB - Cryoglobulinemic vasculitis (CV) presents with systemic manifestations, including
renal disease, arthritis, peripheral neuropathy, and muscle weakness. We
encountered two patients who developed severe nephrotic range proteinuria;
however, extrarenal manifestations were not noted during the clinical course. A
renal biopsy revealed typical membranoproliferative glomerulonephritis (MPGN)
with huge thrombus-like endothelial deposits and predominant IgM positivity, but
electron microscopy did not reveal any definite microtubules. Immunosuppressive
therapy and plasmapheresis were only partially effective, and the improvement was
not durable. Biological therapy with rituximab (RTX) had no effect. Renal-limited
CV should be recognized as a subset of essential CV.
PMID- 29962419
TI - Sclerosing Polycystic Adenosis of Tongue.
AB - Sclerosing polycystic adenosis (SPA) is a rare benign lesion of the salivary
glands which appears histologically similar to sclerosing adenosis and
fibrocystic disease of the mammary gland. To date, 67 cases of SPA have been
reported in the literature, with the lesion arising in the minor salivary glands
in only 9. The present report describes the 10th case of SPA. The patient was a
39-year-old Brazilian man who presented with an asymptomatic nodule on the
ventral surface of the tongue. Based on a clinical diagnosis of benign salivary
gland neoplasm, an excisional biopsy of the lesion was performed.
Histopathological examination showed lobular proliferation of ductal and acinar
elements surrounded by a fibrosclerotic stroma. Many of the ductal structures
exhibited cystic dilatation and were surrounded by periductal fibrosis, which is
consistent with SPA findings. No recurrence of the disease was observed after a 5
year follow-up. A literature review is also discussed, focusing on both the
etiology of SPA and the treatment options available.
PMID- 29962420
TI - Congenital Epulis: A Case and Review of the Literature.
AB - Congenital epulis is an unusual benign oral mucosal lesion in newborns with no
tendency to recur after excision. The histogenesis of the lesion is unknown, but
it is believed to be of mesenchymal origin. We describe a case of congenital
epulis (20*10 mm) in the mandibular gingiva of a newborn. The mass, which was
smooth-surfaced and pedunculated with a healthy color, was surgically removed at
5 months post-birth. Histologically, the tumor consisted mainly of large
eosinophilic granular cells. Immunohistochemical studies revealed intense
staining for vimentin, STRO-1, and CD44, suggesting that it was derived from
mesenchymal cells. The literature and immunohistochemical profile of congenital
epulis are also discussed.
PMID- 29962421
TI - Dental Treatment Effect on Deep Brain Stimulation System in Parkinson's Disease.
AB - Parkinson's disease (PD) is a highly prevalent, long-term neurodegenerative
disorder that is sometimes treated by deep brain stimulation (DBS), which
significantly reduces the need for dopaminergic drug therapy and improves quality
of life. Such patients are cautioned, however, that dental instruments such as a
dental turbine or ultrasonic scaler may adversely affect the functioning of such
a system. Here, we report dental treatment for right maxillary tooth pain in a 65
year-old woman undergoing DBS for PD. The diagnosis was occlusal trauma. After
verification with occluding paper each time, treatment comprised milling of the
high contact points of tooth #17, followed by scaling with an ultrasonic scaler.
This treatment was spread out over 3 visits, and its course was uneventful. To
our knowledge, there are no previous reports on the interaction between dental
instruments and DBS systems. Although no interference with the DBS system was
observed here, we believe that the dentist should be aware of the potential for
such, especially with the use of devices used to measure root canal length,
dental lasers, and electrical scalpels.
PMID- 29962422
TI - Effects of Ultrasonic Debridement on Oral Hygiene Status.
AB - The aim of this randomized-controlled, single-blinded study was to compare the
effects of mechanical tooth cleaning (MTC) and ultrasonic debridement (UD) on
oral hygiene status in healthy young adults. Thirty-seven participants (mean age:
20.3+/-0.62 years) were divided into 3 groups after pre-examination: group A,
receiving MTC; B, receiving MTC+UD using a universal insert (UDUI); and C,
receiving MTC+UD using a probe-shaped insert (UDPI). All participants were
required to abstain from oral hygiene for 24 hours after the allocated
intervention, after which they were examined. A masked examiner determined the
Quigley-Hein plaque index (PlI) and Silness and Loe gingival index (GI) scores
before the interventions and after 24 hours of non-brushing. A significant
increase in the PlI score was observed in group A (p<0.001) in comparison with
that in group B (A: 0.311+/-0.26; B: -0.01+/-0.33; C: 0.13+/-0.27; p<0.05). A
significant decrease in the GI score was observed in groups B and C (p<0.05), and
the change in this score in group C significantly differed from that in group A
or B (A: -0.04+/-0.25; B: -0.13+/-0.17; C: -0.33+/-0.2; p<0.05). Only MTC was
insufficient to prevent plaque formation over a 24-hour period of non-brushing
and decrease the GI score. Ultrasonic debridement was more effective in
preventing plaque formation and decreasing the GI score, regardless of the type
of insert used. The present results suggest that UD should be included as an
important procedure in the provision of professional oral prophylaxis and that
UDPI is as efficient for cleaning as UDUI.
PMID- 29962423
TI - Three-dimensional Finite Element Analysis of Bone Fixation in Bilateral Sagittal
Split Ramus Osteotomy Using Individual Models.
AB - The purpose of this study was to investigate factors involved in stress on
locking mini-plate/screws used in orthognathic surgery based on patient-specific
3-dimensional finite element analysis. Data were obtained from 10 patients
undergoing mandibular advancement by bilateral sagittal split ramus osteotomy.
All underwent osteosynthesis with 2.0-mm titanium locking mini-plate/screws. A 3
dimensional finite element model of the mandible was created for each patient and
each model subjected to the same loading conditions, which produced different
stress values on locking mini-plate/screws. When the contact area of the proximal
and distal bone segments was narrower and bone mineral density (BMD) lower, the
von Mises stress values on the plate/screws were higher (contact area, p<0.01;
BMD, p<0.05). The present results suggest that bone contact area and BMD should
be considered as plate stress factors.
PMID- 29962424
TI - Interleukin-34 Levels in Gingival Crevicular Fluid and Plasma in Healthy and
Diseased Periodontal Tissue in Presence or Absence of Obesity: A Clinico
biochemical Study.
AB - Interleukin (IL)-34 has recently been identified as an alternative ligand for
colonystimulating factor-1 receptor and plays an important role in
osteoclastogenesis. The aim of this study was to assess and compare IL-34 levels
in gingival crevicular fluid (GCF) and plasma in obese individuals in the
presence or absence of periodontal disease and to determine whether they showed a
correlation with disease severity. Forty patients aged between 25 and 40 yr were
enrolled and categorized into 4 groups: 10 non-obese patients with healthy
periodontium (Group I); 10 obese patients with healthy periodontium (Group II);
10 non-obese patients with chronic periodontitis (Group III); and 10 obese
patients with chronic periodontitis (Group IV). Demographic variables such as age
and body mass index score were recorded and assessed, together with clinical
periodontal parameters such as the gingival index, probing pocket depth, and
clinical attachment level scores in all groups. The GCF and plasma levels of IL
34 were quantified using enzyme-linked immunosorbent assay. The results showed
that the mean IL-34 concentrations in GCF or plasma were highest in Group IV,
followed by Group III, Group II, and Group I, with the difference among them
being statistically significant (p<0.05). These results suggest that obese
individuals with periodontitis have higher GCF and plasma IL-34 levels than non
obese individuals with healthy periodontium. This suggests IL-34 as a potential
inflammatory marker of periodontal disease and obesity.
PMID- 29962425
TI - Effect of Mesenchymal Cells on Myoblast Sheets Embedded in Collagen Gel.
AB - The objective of this study was to investigate the effects of mesenchymal cells
on myoblasts in long-term cultivation of myoblast cell sheets. Sheets of
myoblasts and mesenchymal cells from Japanese rabbit oral mucosa were generated
and analyzed by histochemistry, Western blot, and reverse transcription
polymerase chain reaction. The presence of desmin and type IV collagen, which is
seen in normal muscle tissue, was also confirmed in all the sheets produced.
Expression of desmin and type IV collagen showed a decrease under co-culture
conditions. In addition, expression of genes important in maintaining the
undifferentiated state (Pax7, CD34, myogenin, MyoD) in myoblasts was observed
throughout the long cultivation period. Insulin-like growth factor was expressed
only when the mesenchymal cells were co-cultured with myoblasts. These data
suggest that the presence of mesenchymal cells in a long-term co-culture system
influences myoblast differentiation.
PMID- 29962426
TI - Effect of PRF and Allograft Use on Immediate Implants at Extraction Sockets with
Periapical Infection -Clinical and Cone Beam CT Findings.
AB - Immediate implant placement can be successful, even at infected sites. The
adjunctive effects of concomitant use of platelet-rich fibrin (PRF) and
decalcified freeze-dried bone allografts (DFDBA) at periapically infected sites
remains to be determined, however. The purpose of this prospective study was to
investigate the effect of combined use of PRF and DFDBA on immediate implant
survival at tooth extraction sites exhibiting periapical lesions. Implants were
immediately placed in 8 patients under a standard chemotherapeutic protocol. Adin
titanium implants were used in all cases. The combination of PRF and DFDBA was
used to fill the gap between the implant body and the surrounding socket wall.
The final restoration was placed after 3 months. The full-mouth plaque, gingival
bleeding index, and gingival esthetics scores were assessed at 3, 6, and 12
months. Cone beam computed tomography images obtained at baseline and at 12
months after implant loading were analyzed. The plaque index scores showed
statistically significant differences at 3, 6, and 12 months (p<0.05). The
gingival bleeding index score showed no significant difference. No difference was
noted in buccal gingival level on the implant surface or adjacent teeth at 91.7%
of sites. Complete closure of the interproximal space was seen in 91.7% of the
implant sites. Crestal bone levels on all implant surfaces were non-significant.
Implant survival was 91.67% at 12 months. The adjunctive use of PRF with DFDBA at
periapically infected sites yielded a significant reduction in bone resorption
and accelerated bone healing during the initial post-extraction stage. A
significant improvement was achieved in the gingival esthetic score at the
interproximal and midfacial surfaces. The combined use of growth factors with pre
and postoperative broadspectrum antibiotics over a short time resulted in a
higher implant survival rate at the end of the 1 year post-restoration period.
PMID- 29962427
TI - Sex-Specific Association of Serum 25-Hydroxyvitamin D3 with Insulin Resistance in
Chinese Han Patients with Newly Diagnosed Type 2 Diabetes Mellitus.
AB - This study aimed to explore the association between serum 25-hydroxyvitamin D
(25(OH)D) and insulin resistance as well as beta-cell function in Chinese Han
patients with newly diagnosed type 2 diabetes mellitus (T2DM). A total of 264
patients was included in this study. Serum 25(OH)D, plasma glucose, serum insulin
and other biochemical parameters were assayed. Postprandial venous blood was
collected after a mixed-nutrient load. Insulin resistance was assessed by the
homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda insulin
sensitivity index (Matsuda ISI). The beta-cell function was assessed by the
homeostasis model assessment for insulin secretion (HOMA-beta) and the change in
insulin divided by change in glucose from 0 to 30 min (DeltaI0-30/DeltaG0-30).
Patients were divided into three groups according to tertiles of serum 25(OH)D
levels. There were significant differences in HOMA-IR and Matsuda ISI among the
three groups (HOMA-IR, p=0.005; Matsuda ISI, p=0.009). Pearson correlation
analyses showed that serum 25(OH)D was negatively correlated with fasting serum
insulin (FIns) (r=-0.209, p=0.012) and HOMA-IR (r=-0.273, p=0.001), and
positively correlated with Matsuda ISI (r=0.219, p=0.009) only in the male
population. Multiple stepwise regression analyses showed that in the male
population, serum 25(OH)D was an independent predictor for both HOMA-IR and
Matsuda ISI before and after adjustment for confounding factors, respectively
(p<0.05 for both). This study indicates the association of vitamin D with insulin
resistance in male patients with newly diagnosed T2DM, which may contribute to
the understanding of the mechanism underlying the onset of T2DM in the Chinese
Han population.
PMID- 29962428
TI - Comparative Effect between Sardine Oil and Fish Oil Rich in Omega-3 Fatty Acids
on Hypertension and the Membrane Composition of Adipocytes in SHR Rats.
AB - Omega-3 polyunsaturated fatty acids, have an important role in reducing
hypertriglyceridemia, these acids decrease the mortality for Coronary Heart
Disease. Very important is the relationship between fatty acid biosynthesis and
distribution in organs and tissues involved in insulin resistance and
hypertension due to its role in the production of vasoactive eicosanoids and
their effects on insulin sensitivity; which is estimated with the HOMA-IR index,
which relates the physiological and metabolic behavior of glucose and insulin in
the body. The aim of this project was to compare the effect of sardine oil and
omega-3 oils rich in polyunsaturated fatty acids: EPA (~30%) and DHA (~50%)
administered for 6 to 8 wk respectively; on the lipid composition of the plasma
membrane of epididymal adipocytes in spontaneously hypertensive rats (SHR) and
their relation to obesity, insulin resistance and hypertension. The
administration of omega-3 enriched oil significantly decreased the HOMA criteria
as an insulin resistance indicator compared to the sardine oil.
PMID- 29962429
TI - Effects of French Pine Bark Extract Chewing Gum on Oral Malodor and Salivary
Bacteria.
AB - Frequent or persistent malodor (halitosis) represents a considerable
embarrassment to those affected. French pine bark extract, Pycnogenol(r) (PYC),
has displayed antibacterial activity against a broad range of bacterial species.
In the present study, anticipated benefits of PYC on diminishing halitosis were
investigated. Ten healthy males and 11 females, aged 40.1+/-12.3 y, were
recruited based on threshold breath sulfur compounds presence, diagnosed by
portable gas chromatography. Subjects were randomly assigned to either sugar-free
gums, or gums bearing an additional 2.5 mg PYC per piece. The subjects were
required to consume two pieces of PYC or placebo gum six times daily for 15 min.
The levels of volatile sulfur compounds (VSCs), measured by OralChromaTM, and
tongue-coating score were recorded at baseline, 2, and 4 wk. Hydrogen sulfide
producing bacteria in saliva were cultured on Brucella blood agar plates
containing 0.05% cysteine, 0.12% glutathione, and 0.02% lead acetate. The group
consuming PYC chewing gum reduced exhaled hydrogen sulfide, methyl mercaptan and
dimethyl sulfide significantly (p<0.01) after 2 wk versus baseline. Continuation
of daily PYC-gum consumption for 4 wk remarkably lowered the tongue-coating score
and exhaled hydrogen sulfide was significantly decreased compared to the placebo
group. PYC chewing gum significantly reduced hydrogen sulfide-producing bacteria
in saliva after 4 wk (p<0.01), with no effects observed in the placebo control.
The results suggest that PYC chewing gum is effective in reducing oral malodor by
decreasing the accumulation of tongue coating and the number of hydrogen sulfide
producing bacteria in saliva.
PMID- 29962430
TI - L-Lysine Attenuates Hepatic Steatosis in Senescence-Accelerated Mouse Prone 8
Mice.
AB - Non-alcoholic hepatic steatosis is a phenotype of metabolic syndrome, and aging
is a risk factor for this condition. Senescence-accelerated mouse prone 8 (SAMP8)
is a murine model for studying aging-associated disorders. We here investigated
the effect of dietary supplementation with L-lysine (Lys) on non-alcoholic
hepatic steatosis in SAMP8 mice. Triglyceride (TG) and cholesterol (Chol)
accumulated in the livers of SAMP8 mice fed a standard diet at 36 wk of age.
However, intake of a Lys-rich diet for 2 mo prevented the accumulation of TG and
Chol in the liver. Plasma alanine aminotransferase activity, an index of liver
injury, was decreased by Lys. The mRNA expression levels of peroxisome
proliferator-activated receptor gamma coactivator 1-alpha and carnitine
palmitoyltransferase 1a, which regulate beta-oxidation, were increased in the
livers of SAMP8 mice fed the Lys-rich diet. Taken together, our study suggests
dietary intake of Lys prevents hepatic steatosis by stimulating beta-oxidation in
SAMP8 mice.
PMID- 29962431
TI - FGF21 Alleviates Hepatic Endoplasmic Reticulum Stress under Physiological
Conditions.
AB - Fibroblast growth factor 21 (FGF21), mainly synthesized and secreted from the
liver, is an endocrine FGF that regulates glucose and fatty acid metabolism to
maintain whole body energy homeostasis. Gene expression of FGF21 was previously
reported to be induced by endoplasmic reticulum (ER) stress through activating
transcription factor 4 (ATF4). It has been reported that drug-induced ER stress
is reduced by overexpression of FGF21. However, the function of endogenous FGF21
under physiological conditions such as the postprandial state remains unknown.
Here, we examined the effects of both endogenous and exogenous FGF21 on
postprandial hepatic ER stress. In mice, postprandial and tunicamycin-induced ER
stress was significantly reduced by overexpression of FGF21 using a recombinant
adenovirus. FGF21-deficient mice exhibited a more considerable increase in drug
induced ER stress target gene expression than wild-type mice. Following refeeding
after fasting, FGF21 deficiency caused severe ER stress in the liver. The
postprandial ER stress response was significantly reduced when hepatic FGF21 gene
expression was increased by feeding a diet containing the soy protein beta
conglycinin which activates ATF4. Together, these results demonstrate that FGF21
reduces the increased expression of a subset of genes in the liver in response to
ER stress and may correct metabolic disorders caused by ER stress.
PMID- 29962432
TI - Thiamine Concentrations in Newly Hospitalized Elderly Patients with Infectious
Diseases at a Community Hospital in Japan.
AB - The association between advanced age and the thiamine concentration has not been
conclusively determined. A recent report from Japan showed that more than half of
nursing home elderly residents at an institution had a low whole-blood thiamine
concentration (<20 ng/mL). Therefore, a high incidence of low thiamine
concentrations among hospitalized elderly has been anticipated in the Japanese
population but never investigated. We evaluated the whole thiamine concentration
in newly hospitalized elderly patients (>=65 y old) with infectious diseases.
Evaluations were performed on admission and at days 6-8 of hospitalization with
liquid chromatography tandem mass spectrometry (LC/MS/MS). As a result, we
enrolled a total of 471 patients from September 2015 to December 2016. The median
thiamine concentration was 46 ng/mL (IQR, 37-58 ng/mL). Only 7 patients (1%) had
thiamine concentrations below 20 ng/mL (66 nmol/L) on admission. Five of these
patients were bedridden and unable to eat food by themselves, and the other two
patients used loop diuretics for chronic heart failure. The thiamine
concentration declined in most patients (84%) at days 6-8 of admission,
regardless of their dietary intake during hospitalization. In conclusion, a low
thiamine concentration was not prevalent among newly hospitalized elderly
patients with infectious diseases. However, the thiamine concentration
significantly decreased during the 6-8 d of hospitalization.
PMID- 29962433
TI - Quantities of Phospholipid Molecular Classes in Japanese Meals and Prediction of
Their Sources by Multiple Regression Analysis.
AB - Dietary intake of total phospholipids (PLs) accounts for approximately 10% of
total dietary lipids. Each PL molecular class has various beneficial effects on
health. However, limited information is available regarding the intake of
phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol
(PI), phosphatidylserine (PS), lysophosphatidylcholine (LPC) and sphingomyelin
(SM) among Japanese people, and the relevant food sources. In this study, we
quantified the contents of PC, PE, PI, PS, LPC, and SM in 120 meal samples served
in a Japanese company's dormitory and cafeteria. Additionally, we measured the
weight of each food group and estimated the contents of nutrients in these meals.
Furthermore, we conducted a stepwise multiple regression analysis to identify
predictors (food groups) of each PL class intake. The contents of total PL, PC,
PE, PI+PS, LPC, and SM (mean value) were 4.44, 2.17, 0.632, 0.123, 0.313, and
0.127 g/d, respectively. These values were considered as daily PL intake in
accordance with data (three macronutrients, vitamins, and minerals) from our
study and the National Health and Nutrition Survey (NHNS) Japan, 2015. The
content of eggs, meat, fish and shellfish, milk, pulses, fruits, mushrooms,
cereals, and fats and oils in the meals predicted the PL and PC contents. The
content of eggs, pulses, and mushrooms in the meals predicted the PE contents.
Our results determined the daily intake of PL molecular classes among Japanese
people and the food sources of PC and PE, and suggested that multiple regression
analysis is useful for the prediction of food sources of bioactive components.
PMID- 29962434
TI - Group B Soyasaponin Aglycone Suppresses Body Weight Gain and Fat Levels in High
Fat-Fed Mice.
AB - Group B soyasaponins, found in soy, have various health-promoting properties, but
it is unclear whether they have an anti-obesity effect. The aim of this study was
to evaluate the anti-obesity effect of group B soyasaponin glycosides and
aglycone in mice fed a high-fat diet. Six-week-old C57/BL6 mice were divided into
three groups (each n=10) and orally administered a high-fat diet for 35 d; two of
the groups also received group B soyasaponin glycosides or aglycone. Although
there was no significant difference among the three groups in consumption, the
weight of fat adipose tissue at autopsy was more than 30% lower in the group B
soyasaponin aglycone group than in the control group, but X-ray computed
tomography showed no significant difference in muscle weight between these two
groups. The ratio of muscle to whole body weight was higher in the group B
soyasaponin aglycone group than in the control group. These results suggest that
group B soyasaponin aglycone has a stronger anti-obesity effect than group B
soyasaponin glycosides, without a loss in muscle weight, and that it increases
the ratio of muscle to whole body weight. To our knowledge, this is the first
report showing the anti-obesity effect of soyasaponin aglycone in vivo using
animal models.
PMID- 29962435
TI - Vitamin D Attenuates FOXO1-Target Atrophy Gene Expression in C2C12 Muscle Cells.
AB - Vitamin D is known to be effective for the prevention of muscle atrophy, such as
age-related sarcopenia. However, vitamin D action in skeletal muscle tissue and
muscle cells is largely unknown. We previously found that a transcription factor,
FOXO1 gene expression, was induced in various muscle atrophy conditions causing
muscle atrophy by upregulating atrophy-related genes, including atrogin 1
(ubiquitin ligase) and cathepsin L (lysosomal proteinase). In this study, we
found that vitamin D inhibited FOXO1-mediated transcriptional activity in a
reporter gene assay. Moreover, vitamin D suppressed the glucocorticoid-induced
gene expression of atrogin 1 and cathepsin L in C2C12 myoblasts. Thus, vitamin D
may prevent muscle atrophy via the FOXO1-mediated pathway in muscle cells.
PMID- 29962436
TI - Time Course of Decrease in Skeletal Muscle Mitochondrial Biogenesis after
Discontinuation of High-Fat Diet.
AB - It is known that a high-fat diet induces an increase in mitochondrial biogenesis
in skeletal muscle. To examine the time course of decrease in mitochondrial
biogenesis in skeletal muscle after discontinuing a high-fat diet feeding,
C57BL/6 mice were fed a high-fat diet for 4 wk and then switched to the control
diet for another 3 or 7 d. During the high-fat diet withdrawal period, the
protein content of the mitochondrial respiratory chain decreased faster than the
fatty acid oxidation enzymes. The mitochondrial DNA copy number remained high for
at least 1 wk after withdrawing the high-fat diet. These results suggested that
after switching to the control diet following a period of high-fat diet, the
increased mitochondrial biogenesis levels are maintained for a few days, and the
rate of decline is divergent between the different mitochondrial components.
PMID- 29962437
TI - The Response Time of the Stroop Test Is Delayed during Lemon-Flavored Gum
Chewing.
AB - In the present study, we examined the cognitive function during mastication of
lemon-flavored gum, which is said to enhance cerebral blood flow. Nine healthy
subjects (8 female and 1 male) participated in this study. Subjects chewed the
gum for 3 min after fasting for 2 h and conducted a Stroop test while continuing
to chew. At the end of all answers, gum chewing ended. The response time in the
Stroop test was used as an indicator of cognitive function. We set the three
conditions (lemon-flavored gum, mint-flavored gum, no gum chewing). There was no
significant difference in reaction time between chewing mint-flavored gum and not
chewing (p>0.05). However, the response time during chewing gum with a lemon
flavor was significant slower than the conditions with mint-flavored gum and
without gum chewing (p<0.05, in both). From the results of the present study, it
was suggested that the response time delay of the Stroop test observed during the
chewing of lemon-flavored gum revealed temporary decay of cognitive function
during lemon-flavored gum chewing. It is suggested that lemon-flavored chewing
gum forces a brain overload, resulting in a temporary decrease in cognitive
function.
PMID- 29962438
TI - [Cytomegalovirus myositis complicated with hemophagocytic lymphohistiocytosis,
acute renal failure, and colitis].
AB - A 60-years-old previously healthy man presented with acute renal failure and
hemophagocytic lymphohistiocytosis (HLH). Both conditions improved after
immunotherapies, but severe limb weakness with elevation of serum CK developed.
Needle EMG showed myogenic changes with spontaneous activities and muscle
weakness thereafter improved without adding further immunotherapies, suggesting
that our patient had viral myositis. After the stabilization of limb weakness,
cecal perforation occurred due to cytomegalovirus (CMV) enteritis and temporal
significant change of anti-CMV IgG antibody titer was confirmed using paired
serum samples. Upregulation of MHC-class I molecule and numerous regenerative
muscle fibers were observed in muscle biopsy, but no evidence of direct CMV
infection in muscle fibers were seen. Although CMV infection may cause either
myositis, acute renal failure, HLH or colitis in individual patient, this is the
first case which had been complicated by all these conditions subsequent to CMV
infection.
PMID- 29962439
TI - [A case of hemichorea associated with lung adenocarcinoma].
AB - An 81-year-old woman admitted to our hospital due to involuntary movement on her
right extremities. Laboratory tests, including autoantibodies, were unremarkable
and only age related changes were observed on brain MRI. Chest CT revealed lung
adenocarcinoma. She was diagnosed as having paraneoplastic chorea. After removal
of the tumor, her chorea was dramatically improved. One year after the operation,
abnormal high intensity lesions were seen in bilateral caudate nuclei and globus
pallidus on MRI. A part of the left caudate nucleus was enhanced by gadolinium.
Here we show a clinical picture and neuroradiological findings of paraneoplastic
chorea associated with lung adenocarcinoma.
PMID- 29962440
TI - [A pedigree of hereditary hyperekplexia].
AB - A 31-year old women presented with excessive startle reflex and frequent falls.
Her startle reflex is induced by slight stimuli which are not problematic in most
people. Soon after her startle reflex is evoked, generalized muscle stiffness
occurs. She becomes rigid and falls down without loss of consciousness. Because
she cannot protect herself when she is startled and falls, she has repeatedly
bruised her head and face. The pedigree includes her father and two sisters with
similar symptoms. Gene analysis revealed GLRA1 mutation, and she was diagnosed
with hereditary hyperekplexia (HPX). Symptoms improved with clonazepam 1 mg/day.
HPX patients live with severe anxiety about frequent falls and sometimes suffer
serious injury, such as cerebral concussion or bone fracture. Although HPX might
sometimes be underestimated, accurate diagnosis is very important for effective
treatment.
PMID- 29962441
TI - [A 36-year-old woman with primary central nervous system lymphoma diagnosed by
twice brain biopsies, showing relapsing and remitting brain lesions].
AB - A 36-year-old woman visited a local hospital suffering from acute onset
dizziness. Brain MRI revealed multiple white matter lesions without gadolinium
enhancement in the both hemispheres. Although she began to receive a treatment
under a clinical diagnosis of multiple sclerosis, she developed newly emerging
brain lesions and was referred to our hospital. Neurological examination detected
intention tremor, right-sided dysdiadochokinesis, and gait ataxia. Both blood and
cerebrospinal fluid tests were unremarkable but follow-up brain MRIs showed
rapidly relapsing and remitting lesions. The first brain biopsy ended up showing
non-specific changes but the second biopsy with five months interval confirmed
primary central nervous system lymphoma (PCNSL). The patient was treated by
chemotherapy and showed partial response. It is important to consider sequential
brain biopsies if needed because PCNSL may present diverse brain lesions on MRI
including non-neoplastic early lesions.
PMID- 29962442
TI - [A case of neurosarcoidosis with recurrent brainstem infarction, obstructive
hydrocephalus and brainstem atrophy].
AB - We report the case of a 42-year-old female with neurosarcoidosis who was
hospitalized in year 2017 for gait disturbance. In 2011, she suddenly had vertigo
that lasted for a few days. In 2013, she noticed left hemiplegia. A brain MRI
revealed an acute infarction on the right side of the upper pons extending
longitudinally from the ventral surface. In 2017, she again had left lower limb
paralysis. A Brain MRI showed another infarction on the right side of the mid
pons. Hydrocephalus and brainstem atrophy were also noted. The patient was
referred to our hospital. Upon neurological examination, she presented with down
beat nystagmus, muscle weakness on the left side, and a broad-based spastic gait.
CSF findings included an increased number of cells and protein levels with
decreased glucose levels. A contrast-enhanced MRI revealed basilar meningitis
causing hydrocephalus. A contrast CT scan revealed inguinal lymph node swelling,
and scintigram found gallium accumulation. We diagnosed sarcoidosis via a lymph
node biopsy. We speculate that chronic basilar meningitis obstructed the
patient's branching penetrating arteries inducing infarction together with
obstruction of the spinal fluid flow causing hydrocephalus and cerebral atrophy.
PMID- 29962443
TI - [A case of body lateropulsion to the left in acute cerebral infarction of the
right medial parietal lesion].
AB - A 68-year-old right-handed woman with acute-onset inability to stand was admitted
to our department. Although left hemiparesis was minor, the neurological
examination on admission showed marked body lateropulsion (BL) to the left when
she stood or stepped with eyes open and feet closed. Neither ataxia nor sensory
disturbance was present. Brain MRI and 3D-CT angiography revealed infarction of
the right posterior cingulate and the precuneus due to dissection of the right
anterior cerebral artery. BL improved on day 10 and she was discharged without
sequelae on day 26. BL caused by cerebral lesions is rare, and we should
recognize that infarction of the posterior cingulate and/or the precuneus can
cause BL.
PMID- 29962445
TI - [Development of public health system since the incunabula age until today].
PMID- 29962444
TI - [Misleading cerebral arterial wall gadolinium-enhancement in malignant lymphoma].
AB - A previously healthy, 77-year-old woman presented with gradual cognitive decline
and acute gait imbalance. On admission, despite no obvious paralysis, she tilted
to the right. Her Mini-Mental State Examination score was slightly low (23/30).
Gadolinium-enhanced, high-resolution T1-weighted MRI showed abnormal arterial
wall enhancement at the bilateral middle cerebral and right internal carotid
arteries. The combination of arterial and parenchymal enhancement limited to the
central nervous system (CNS), normal laboratory data including soluble
interleukin-2 receptor, and random skin and bone-marrow biopsies was suggested of
primary angiitis of the CNS (PACNS). However, a biopsy specimen from the right
insula showed CD20-positive lymphoma cells indicative of diffuse large B-cell
lymphoma. After receiving chemotherapy, above-mentioned abnormal findings were
significantly improved. Considering the increasing clinical application of high
resolution MRI, there is a risk that patients may receive a presumptive diagnosis
of PACNS and immunosuppressive treatment without biopsy confirmation. It should
be noted that a combination of abnormal arterial wall and linear parenchymal
enhancement similar to that found for PACNS on high-resolution MRI may occur in
patients with primary central nervous system lymphoma.
PMID- 29962446
TI - [Occupational stress among care workers: evaluation by a novel physiological
method].
AB - Objectives In this report, I studied the occupational stress response in care
workers using a novel physiological method. Specifically, I evaluated the
individual level of stress response in these care workers and further examined
the relationship between the stress responses and various types of jobs.Methods
This study included 35 care workers working at different geriatric health
facilities. During working hours, the stress response levels of these care
workers were evaluated based on the changes in their sympathetic functions as
measured by frequency analysis of an electrocardiogram and recorded using Holter
electrocardiography. Additionally, workers were asked to maintain a diary to
record the types of work they performed throughout the day. Based on the
collected data, I examined the stress response values and determined their
associations with different types of work. Levels of salivary chromogranin A
(CgA) protein were also measured in the participating care workers.Results The
maximum job stress index (i.e., the strongest job-related stress response
exhibited during the day) and CgA concentrations were significantly higher in the
shift-change group than the regular-shift group (maximum job stress index: 26.2+/
12.0 vs. 16.1+/-6.5, CgA protein: 10.8+/-14.6 vs. 2.3+/-1.2 pmol/mg; P<0.05 for
both measurements). For the day-shift group, the job stress index (i.e., stress
response while performing a job) and job stress peak value (i.e., peak value of
stress response while performing a job) were significantly higher for the worker
groups performing inter-professional tasks (148.9+/-27.0, 29.8+/-9.1,
respectively) and oral care (82.4+/-16.7, 15.4+/-8.7, respectively) than the
groups involved in other jobs. The job stress peak value was also significantly
high (20.5+/-9.6) for the bathing care worker group. For the night-shift worker
groups, the job stress index and job stress peak value were significantly higher
for oral care and clothing care groups than the groups performing other jobs
(oral care: 100.1+/-23.1, 17.6+/-8.6; clothing care: 102.8+/-22.8, 19.8+/-11.7).
Interestingly, for the sheet-changing group, the job stress index and job stress
peak value were significantly higher for the night-shift group than the day-shift
group (night: 120.6+/-23.3, 25.7+/-10.9; day: 65.0+/-10.6, 16.4+/
10.9).Conclusions In this study, I present a novel method for analyzing the
occupational stress responses in care workers; this method employs frequency
analysis of an electrocardiogram and measurement of the salivary concentration of
CgA protein. Further, the stress response in these workers appeared to be
enhanced by changing their shift schedules. In conclusion, inter-professional
tasks, oral care, and tasks requiring the caregivers to touch patients were found
to be stressful jobs. Interestingly, the stress response among sheet-changing
workers seemed to differ between night and day shifts.
PMID- 29962447
TI - [Support that cancer peer supporters working at medical institutions currently
receive and the support they actually need].
AB - Objectives This research aims to ascertain the kinds of support cancer peer
supporters at medical institutions currently receive and the support they
actually need.Methods Participants in the study were ten cancer peer supporters
who were recommended by a patient association and who agreed to participate in
the study. Using a qualitative descriptive method, interviews were conducted
using an interview guide from July to October 2014. Codes were extracted from the
interview transcript and divided into categories and subcategories. Accuracy was
ensured by checking the data with the participants. The study was conducted with
the approval of the Ethics Committee of Mejiro University.Results Research
participants consisted of two men and eight women aged forty to seventy years,
who were private counselors, telephone counselors, or members of cancer salons at
hospitals. Four categories were generated on the basis of the support that cancer
peer supporters are currently receiving: mutual learning and support among peer
supporters, learning and encouragement from patients, self-improvement in peer
supporters, and cooperation with hospitals and the government. Seven categories
were generated on the basis of the support that cancer peer supporters need:
opportunities for peer supporters to learn from and support each other, further
studies on cancer peer support, reliable and up-to-date information, society's
understanding and cooperation regarding cancer, financial support for support
activities and patient associations, improvement of cancer peer support system,
and quality assurance of peer supporter training courses.Conclusion Cancer peer
supporters were supporting each other, gaining encouragement from patients,
improving themselves, and gaining support from others. However, they also needed
additional assistance such as opportunities for supporters to learn from and
support each other and reliable and up-to-date information. Moreover, peer
supporters needed advice and emotional support from hospital staff as they
experienced difficulties during consultation. Various other types of support were
needed, such as society's understanding and cooperation regarding cancer,
financial support for support activities and patient associations,
institutionalization of peer supporter placement in hospitals, and quality
assurance of peer supporter training courses. Overall, support for cancer peer
supporters is still not sufficient; thus, further help is necessary.
PMID- 29962448
TI - [Examining the validity of the finger rub/finger tap screening test for the early
detection of age-related hearing loss].
PMID- 29962449
TI - [Personality and dietary supplement use among Japanese female students].
AB - Objectives The purpose of this study was to examine the relationship between
dietary supplement use and personality traits among Japanese female
students.Methods A cross-sectional questionnaire survey was administered to 230
female university or junior college students in October and November 2015; 228
students responded. The questionnaires inquired regarding the usage of dietary
supplements and attitudes about dietary supplements, as well as the healthy
eating literacy (HEL) scale and the Big Five personality traits. In total, 124
respondents completed the survey. The Mann-Whitney U test, Kruskal-Wallis test,
chi-square test, and Spearman's correlation coefficient were used to examine
dietary supplement-personality relationships.Results Overall, 19.4% of students
reported using dietary supplements. Supplement users had high extraversion scores
compared with non-users. Attitudes about dietary supplements and HEL were not
associated with personality traits.Conclusion Personality traits influenced
dietary supplement use, although limitedly.
PMID- 29962450
TI - Maca Cosmetics: A Review on Constituents, Therapeutics and Advantages.
AB - Herbal cosmetics are the focus of attention nowadays, they have various
therapeutics, including, anti-oxidant, anti-radiation, anti-aging, anti
inflammatory. Maca contains polysaccharides, phenolics, alkaloids, minerals and
amino acids, which is said to suitable component for cosmetics due to the single
action or synergy action. The review summarized the existed and potential
therapeutic effects of maca ingredients in cosmetics. And compared to the
marketed cosmetics, maca cosmetics have the merits of mild, low-toxicity and the
clear relationship efficacy.
PMID- 29962451
TI - Nanostructured Fat Crystal and Solid Fat Content Effects on the Physical
Properties of Water-in-Oil Semisolid Fat Blends.
AB - The effect of nanostructured fat crystals on oil migration properties in water-in
oil-type emulsified semisolid fats was investigated. Model emulsions containing 4
different semisolid fats (palm oil, partially hydrogenated palm oil, partially
hydrogenated soybean oil, and milk fat) and 1 bulk fat blend were prepared with
rapidly cooling crystallization. The length of the nanoplatelets was observed by
cryo transmission electron microscopy, the crystal thickness was calculated by
small-angle X-ray diffraction, and the solid fat content (SFC) was determined.
Although the interfacial surface of the dispersed water droplets did not
influence nanoplatelet size, oil migration in the emulsified samples was lower
than in the bulk fat. The crystal sizes in samples with partially hydrogenated
soybean oil involving elaidic acid were larger, in contrast to that of milk fat,
involving low to medium chain length fatty acids, which had smaller crystal sizes
and showed wide length distribution. The length of the platelets and SFC were
related to the oil migration value. These results suggest that the oil binding
ability of fat products, such as margarine, is influenced by the nanostructure,
which is related to fatty acid composition and interfacial structure.
PMID- 29962452
TI - Proteomic Lung Analysis of Mice with Ventilator-Induced Lung Injury (VILI) Using
iTRAQ-Based Quantitative Proteomics.
AB - Ventilator-induced lung injury (VILI) has implications for mortality from acute
lung injury (ALI) and for acute respiratory distress syndrome (ARDS) patients;
the complicated mechanisms of VILI have not been well defined. To discover new
biomarkers and mechanisms of VILI, isobaric Tag for Relative and Absolute
Quantitation (iTRAQ)-based quantitative proteomics were applied to identify
differentially expressed proteins in mice treated with high tidal volume
ventilation (HV), low tidal volume ventilation (LV) and lipopolysaccharide (LPS).
A total of 14 dysregulated proteins showed the same change trend both in the LV
and HV group and no change in the LPS group, and most importantly, the fold
change of these proteins increased with the increase of volume ventilation, which
indicates these proteins may be considered as potential markers specific for
VILI. Ingenuity pathway analysis (IPA) canonical pathways analysis identified the
top 4 canonical pathways, including the extrinsic prothrombin activation pathway,
coagulation systems, the intrinsic prothrombin activation pathway and the acute
phase response, suggesting that these pathways, as associated with these
proteins' expression, may be important therapeutic targets for reducing VILI.
These findings will provide a new perspective for understanding the pathogenesis
of VILI in the future.
PMID- 29962453
TI - Development of a Dissolution Method for Gliclazide Modified-Release Tablets Using
USP Apparatus 3 with in Vitro-in Vivo Correlation.
AB - Gliclazide (GLZ) is a second generation hypoglycemic drug used for the treatment
of Type 2 diabetes mellitus. The low solubility of GLZ has been described as the
rate limiting step for drug dissolution and absorption, thus a prediction of its
in vivo behavior based on a discriminative dissolution test should lead to a
relevant in vitro-in vivo correlation (IVIVC). The aim of this study was to
develop a dissolution method for GLZ modified-release (MR) tablets using an
United States Pharmacopeia (USP) apparatus 3 through its evaluation by an IVIVC
analysis. Various dissolution parameters were evaluated to establish an in vitro
method for GLZ tablets. The final dissolution conditions, referred to as method
3, utilized a 400 um mesh and 30 dips per minute over a total period of 10 h that
included 1h in HCl media (pH 1.2), 2h in acetate buffer solution (pH 4.5), 1 h in
phosphate buffer solution (PBS; pH 5.8), 5h in PBS (pH 6.8) and finally 1h in PBS
(pH 7.2). The calculated point-to-point IVIVC (R2=0.9970) was significantly
greater than other methods. The robustness of method 3 suggests it could be
applied to pharmaceutical equivalence studies and for quality control analyses of
GLZ.
PMID- 29962454
TI - Carotenoid Stereochemistry Affects Antioxidative Activity of Liposomes Co
encapsulating Astaxanthin and Tocotrienol.
AB - We previously found that antioxidative activity of liposomes co-encapsulating
astaxanthin (Asx) and tocotrienols (T3s) was higher than the calculated additive
activity, which results from intermolecular interactions between both
antioxidants (J. Clin. Biochem. Nutr., 59, 2016, Kamezaki et al.). Herein, we
conducted experiments to optimize Asx/alpha-T3 ratio for high antioxidative
activity, and tried to elucidate details of intermolecular interaction of Asx
with alpha-T3. Higher activity than calculated additive value was clearly
observed at an Asx/alpha-T3 ratio of 2 : 1, despite two alpha-T3 would
potentially interact with two terminal rings of one Asx. The synthetic Asx used
in this study was a mixture of three stereoisomers, 3R,3'R-form (Asx-R), 3S,3'S
form (Asx-S) and 3R,3'S-meso form (Asx-meso). The calculated binding energy of
the Asx-S/alpha-T3 complex was higher than those of Asx-R/alpha-T3 and Asx
meso/alpha-T3, suggesting that Asx-S and alpha-T3 is the most preferable
combination for the intermolecular interaction. The optimal Asx-S/alpha-T3 ratio
for antioxidation was shown to be 1 : 2. These results suggest that the Asx
stereochemistry affects the intermolecular interaction of Asx/alpha-T3. Moreover,
the absorption spectrum changes of Asx-S upon co-encapsulation with alpha-T3 in
liposomes indicate that the electronic state of Asx-S is affected by
intermolecular interactions with alpha-T3. Further, intermolecular interactions
with alpha-T3 affected the electronic charges on the C9, C10 and C15 atoms in the
polyene moiety of Asx-S. In conclusion, the intermolecular interaction of Asx/T3
depends on the Asx stereochemistry, and caused a change in the electronic state
of the Asx polyene moiety by the presence of double bond in the T3 triene moiety.
PMID- 29962455
TI - Detoxification Mechanism of alpha,beta-Unsaturated Carbonyl Compounds in
Cigarette Smoke Observed in Sheep Erythrocytes.
AB - Highly reactive alpha,beta-unsaturated carbonyl compounds, such as acrolein
(ACR), crotonaldehyde (CA) and methyl vinyl ketone (MVK), are environmental
pollutants present in high concentrations in cigarette smoke. We have previously
found that these carbonyl compounds in cigarette smoke extract (CSE) react with
intracellular glutathione (GSH) to produce the corresponding GSH-ACR, GSH-CA and
GSH-MVK adducts via Michael addition reaction. These adducts are then further
reduced to the corresponding alcohol forms by intracellular aldo-keto reductases
in highly metastatic mouse melanoma (B16-BL6) cells and then excreted into the
extracellular fluid. This time, we conducted a similar study using sheep
erythrocytes and found analogous changes in the sheep erythrocytes after exposure
to CSE as those with B16-BL6 cells. This indicates similarity of the
detoxification pathways of the alpha,beta-unsaturated carbonyl compounds in sheep
blood cells and B16-BL6 cells. Also, we found that the GSH-MVK adduct was reduced
by aldose reductase in a cell-free solution to generate its alcohol form, and its
reduction reaction was completely suppressed by pretreatment with epalrestat, an
aldose reductase inhibitor, a member of the aldo-keto reductase family. In the
presence of sheep blood cells, however, reduction of the GSH-MVK adduct was
partially inhibited by epalrestat. This revealed that some member of the aldo
keto reductase superfamily other than aldose reductase is involved in reduction
of the GSH-MVK adduct in sheep blood. These results suggest that blood cells,
mainly erythrocytes are involved in reducing the inhalation toxicity of cigarette
smoke via an aldo-keto reductase pathway other than that of aldose reductase.
PMID- 29962456
TI - Strength Simulation of Scored Tablets Based on the Finite Element Method Using an
Extreme Vertices Design.
AB - The mechanical strain distribution of scored tablets was simulated using the
finite element method (FEM). The score was fabricated as a triangular runnel with
the pole on the top surface of flat tablets. The effect of diametral compression
on the tablet surface strain was evaluated by changing the angle between the
scored line and the diametral compression axis. Ten types of granules were
prepared according to an extreme vertices design. Young's modulus and the Poisson
ratio for the model powder bed were measured as elastic parameters. The FEM
simulation was then applied to the scored tablets represented as a continuous
elastic model. Strain distributions in the inner structure of the tablets were
simulated after the application of external force. The maximum principal strain
(epsilon1) value was obtained with tablets containing a large amount of corn
starch, in all scored line positions. In contrast, the epsilon1 value of the
tablets containing a large amount of microcrystalline cellulose was minimal. The
adequacy of the simulation was evaluated by experiments with scored tablets. The
results indicated a fairly good agreement between the FEM simulation and
experiments. Moreover, it was found that the epsilon1 value correlated negatively
with the value of tablet hardness. These results suggest that the FEM simulation
was advantageous for designing scored tablets.
PMID- 29962457
TI - Synthesis and Antimicrobial Activity of 2-Trifluoroacetonylbenzoxazole Ligands
and Their Metal Complexes.
AB - Three 2-fluoroacetonylbenzoxazole ligands 1a-c and their new Zn(II) complexes 2a
c have been synthesized. In addition, syntheses of new metal [Mg(II), Ni(II),
Cu(II), Pd(II), and Ag(I)] complexes from 1a have been also described. The
molecular and crystal structures of six metal complexes 2b and 2d-h were
determined by single-crystal X-ray diffraction analyses. Their antibacterial
activities against six Gram-positive and six Gram-negative bacteria were
evaluated by minimum inhibitory concentrations (MIC), which were compared with
those of appropriate antibiotics and silver nitrate. The results indicate that
some metal compounds have more antibacterial effects in comparison with free
ligands and have preferred antibacterial activities that may have potential
pharmaceutical applications. Noticeably, the Ag(I) complex 2h exhibited low MIC
value of 0.7 uM against Pseudomonas aeruginosa, which was even superior to the
reference drug, Norfloxacin with that of 1.5 uM. Against P. aeruginosa, 2h is
bacteriostatic, exerts the cell surface damage observed by scanning electron
microscopy (SEM) and is less likely to develop resistance. The new 2h has been
found to display effective antimicrobial activity against a series of bacteria.
PMID- 29962458
TI - Alkylated Benzoquinones: Ardisiaquinones A-H from the Leaves of Ardisia
quinquegona and Their Anti-Leishmania Activity.
AB - Eight alkylated benzoquinone derivatives, named ardisiaquinones A-H, were
isolated together with four known compounds from the leaves of Ardisia
quinquegona using a combination of different chromatography techniques. Their
structures were elucidated by spectroscopy and by the preparation of methyl
ethers. Anti-Leishmania activity and cytotoxicity of the isolated compounds were
assayed. Some compounds showed moderate anti-Leishmania activity, however, always
associated with cytotoxicity.
PMID- 29962460
TI - Errata for Chemical and Pharmaceutical Bulletin.
PMID- 29962459
TI - Organocatalytic Direct alpha-Selective N-Glycosylation of Amide with Glycosyl
Trichloroacetimidate.
AB - Through the synergistic catalytic effect of the halogen bond (XB) donor and
thiourea catalyst, a direct alpha-selective N-glycosylation of the amide residue
of asparagine derivative was achieved using readily accessible glycosyl
trichloroacetimidate. n-Butyl methyl ether was found to be the most suitable
solvent for the alpha-selectivity.
PMID- 29962461
TI - [Platform Development for Drug Discovery Utilizing Silkworm towards "Novel
Industrial Revolution"].
PMID- 29962462
TI - [Construction of a Platform for the Development of Pharmaceutical and Medical
Applications Using Transgenic Silkworms].
AB - We have been constructing a platform for the development of pharmaceutical and
medical applications using the domesticated silkworm, Bombyx mori, as a new
animal model for drug development and evaluation. Because silkworm larvae
originally have the capacity to synthesize up to 0.5 g of silk proteins,
genetically modified silkworms (transgenic silkworms) are expected to have high
potential in the production of recombinant silks/proteins. An innovative method
for generating transgenic silkworms was established in 2000, and ever since this
epoch-defining technological development, longstanding efforts have succeeded in
developing novel silks that enable the manufacture of new textile materials for
regenerative medical uses. Furthermore, we have succeeded in developing a new
system of recombinant protein production. This recombinant protein production
system is currently capable of producing a maximum of approximately 15 mg
recombinant protein per silkworm larva. Transgenic silkworms have also been shown
to produce a wide variety of useful proteins, including antibodies and membrane
proteins. Some of these recombinant proteins have been in commercial use since
2011. In addition, we have been developing transgenic silkworms as a novel animal
model for testing medicines based on metabolic similarities between silkworms and
mammals. These applications show the suitability and potential of transgenic
silkworms for medical use. Here, we will describe the challenges faced in
creating a transgenic silkworm-based platform for pharmaceutical and medical
applications.
PMID- 29962463
TI - [Development of Large Scale Silkworm-rearing Technologies for the GMP Production
of Biologics].
AB - There exists an increasing need to produce useful proteins in recombinant
technologies. In particular, most biologics for medical purposes are produced as
recombinant proteins. Various host cell/vector systems have been developed, but
it remains difficult to efficiently produce large molecular weight proteins with
complex structures. As a result of breeding for several thousand years, the
silkworm has acquired the ability to synthesize bulk amounts of silk proteins. To
utilize this capacity for the mass production of useful proteins, transgenic
silkworms have been generated that synthesize recombinant proteins in the silk
gland and secrete them into the silk cocoon. Using this transgenic silkworm
system, various proteins, including antibodies, collagen, and fibrinogen, have
been successfully produced and are being developed as materials for diagnostic or
research-use reagents, as well as for cosmetics. Moreover, several silkworm
produced proteins are being developed as biologics for therapeutic use.
Transgenic silkworms need to be reared under good manufacturing practices (GMP)
compliant conditions to produce biologics. Therefore, we have constructed a GMP
compliant pilot plant for producing biologics using transgenic silkworm, and are
now developing silkworm-rearing technology under GMP-compliant conditions.
PMID- 29962464
TI - [Development of Enzyme Drugs Derived from Transgenic Silkworms to Treat Lysosomal
Diseases].
AB - Lysosomal storage diseases (LSDs) are inborn errors caused by genetic defects of
lysosomal enzymes associated with the excessive accumulation of natural
substrates and neurovisceral manifestations. Until now, enzyme replacement
therapy (ERT) with human lysosomal enzymes produced by genetically engineered
mammalian cell lines has been applied clinically to treat several LSDs. ERT is
based on the incorporation of N-glycosylated lysosomal enzymes through binding to
glycan receptors on the surface of target cells and delivery to lysosomes.
However, ERT has several disadvantages, including difficulty in mass producing
human enzymes, dangers of pathogen contamination, and high cost. Recently, we
have succeeded in producing transgenic silkworms which overexpress human
lysosomal enzymes in silk glands, and have purified active and functional enzymes
from middle silk glands and cocoons. Silk gland- and cocoon-derived human enzymes
carrying high-mannose and pauci-mannose N-glycans are endocytosed by monocytes
via the mannose receptor pathway; these were then delivered to lysosomes. Human
cathepsin A (Ctsa) precursor proteins purified from the cocoons have been found
to suppress microglial activation in the brains of Ctsa-deficient mice; this
deficiency is caused by a splicing defect, and serves as a galactosialidosis
model associated with the combination of a deficiency of lysosomal neuraminidase
1 (NEU1) and the accumulation of sialyloligosaccharides. Transgenic silkworms
overexpressing human lysosomal enzymes in silk glands could serve as a future
bioresource to provide safe therapeutic enzymes for the treatment of LSDs. The
combination of recent developments in transglycosylation technology with
microbial endoglycosidases will aid in the development of therapeutic
glycoproteins as bio-medicines.
PMID- 29962465
TI - [Development of Antibiotics Using Silkworm Bacteria and Fungi Infection Model].
AB - The emergence of antimicrobial resistant (AMR) bacteria has become a serious
threat to public health. It is important that we find a mechanistically novel
antibiotic to combat AMR. However, finding compounds which are both
therapeutically effective and safe is difficult in the development of
antibiotics. To solve these problems, we have focused on the silkworm model,
which is economical and poses fewer ethical issues, as a means to evaluate the
therapeutic effectiveness of test compounds in early stages of antibiotic
development. Actually, the silkworm has pharmacokinetic parameters similar to
mammals, and we revealed that antibiotics showed ED50s consistent with mammalian
models. Thus, we screened therapeutically effective samples from natural products
using the silkworm model, and found 23 candidates out of 15000 samples. We
ultimately identified a novel antibiotic, lysocin E, and found that it
demonstrates a potent therapeutic effect in the mouse systemic infection model.
Furthermore, since the target of lysocin E is menaquinone on the bacterial
membrane, it belongs to a novel class of antibiotics. In addition, we found a
novel antibacterial agent named nosokomycin, GPI0363, and an antifungal agent, VL
2397 (ASP2397), using the silkworm model. In this report, we introduce the
usefulness of the silkworm model in the development of antibiotics.
PMID- 29962466
TI - [Forefront of Cancer Targeting Therapy].
PMID- 29962467
TI - [Development of a Fundamental Technology to Seek Drug Targets, and Its
Application to Cancer Targeting Therapy].
AB - Human epidermal growth factor receptor 2 (Her2)-targeting antibodies and anti
hormone therapy are effective for most breast cancer patients. However, such
approaches are not viable with resistant cases or in triple-negative breast
cancer (TNBC) patients, given the lack of Her2 and estrogen and progesterone
receptors in these patients. Thus, new drug targets are urgently required. From
this perspective, we searched for novel drug targets using proteomic analysis,
and identified Eph receptor A10 (EphA10), which is elevated in breast cancer
cells as compared to normal breast tissue. Here, we evaluated the potential of
EphA10 as a drug target by analyzing its protein expression profile/function in
cancer cells, and then by using an anti-EphA10 antibody to treat EphA10
expressing tumor-bearing mice. Protein expression profile analysis showed that
EphA10 was expressed in various breast cancer subtypes, including TNBCs, with no
expression observed in normal tissues, apart from the testes. Moreover,
functional analysis of the cancer cells revealed that ligand-dependent
proliferation was observed in EphA10-expressed cancer cells. Thus, we developed
our novel anti-EphA10 antibody, which binds to EphA10 with high specificity and
affinity at the nanomolar level. Finally, therapeutic analysis indicated that
tumor growth was significantly suppressed in the mAb-treated mice in a dose
dependent manner. These results suggest that the EphA10-targeting therapy may be
a novel therapeutic option for the management of breast cancer, including in
TNBCs which aren't currently treated with molecular-targeted agents.
Consequently, we hope that these findings will contribute to the development of a
new targeting therapy for refractory breast cancer patients.
PMID- 29962468
TI - [Design of New Cancer Nanotherapeutics Which Controls Active Gaseous Molecules in
Vivo].
AB - Reactive oxygen species (ROS) are known to play a variety of roles in many
important events in vivo. However, the overproduction of ROS causes serious
adverse effects to living beings. Numerous drugs have been developed and applied
to reduce overproduced ROS, but these have failed to be clinically approved.
Since most of these antioxidants are low molecular weight (LMW) compounds, they
not only eliminate ROS related to diseases, but also destroy the essential redox
reactions necessary for basic energy production in living bodies. In the
mitochondria of normal cells, ATP production by electron transport chain is
carried out, and a large amount of ROS is thus generated; however, LMW
antioxidants also nonspecifically enter normal cells and affect essential
oxidation. To improve selective antioxidant properties without damage to these
normal redox reactions, we designed new polymer antioxidants. These polymers have
self-assembling properties and form nanoparticles (RNPs) in which nitroxide
radicals covalently attach as a side chain of the hydrophobic segment in the
amphiphilic block copolymers, which are then compartmentalized into the solid
core of the nanoparticles. Unlike LMW antioxidants, RNPs have extremely poor in
vivo toxicity, as they are less likely to be taken up by healthy cells. Since one
of RNPs, RNPN has pH-sensitive disintegration properties, it disintegrates at pH
lower than 7.0 such as solid tumors and inflammation. It can therefore be used in
pH responsive bioimaging and therapy. We have used RNPs experimentally in the
treatment of several diseases and confirmed their effectiveness.
PMID- 29962469
TI - [Development of Ultrasound Theranostics for Cancer].
AB - Theranostics is a term used to describe the combination of diagnostic and
therapeutic functions in a single agent. Ultrasound, for example, is a good tool
for theranostics due to its multi-potency as both a diagnostic tool using
sonography, and as a therapeutic, i.e., by high intensity focused ultrasound
(HIFU). Likewise, microbubbles and nanobubbles are not only used as contrast
imaging agents, but also as enhancers of drug delivery. Recently, the combination
of these bubbles with low intensity ultrasound has been utilized as an effective
drug delivery system. We have implemented a similar technique by combining
bubbles and ultrasound to study cancer gene therapy and chemotherapy. In
addition, we have used high intensity ultrasound as a method for directly
damaging tumor cells, thus serving as a cancer therapy. For effective cancer
treatment, however, the properties of the bubbles are of utmost importance.
Currently, we are applying these bubbles to various therapeutic strategies in
cancer treatment. In this session, we would like to introduce the feasibility
study of our use of these bubbles in cancer treatment.
PMID- 29962470
TI - [Development of an Anticancer Therapy Using Recombinant Bifidobacterium as a New
Drug Delivery System (DDS)].
AB - Intravenously administered obligate anaerobic bacteria, such as bifidobacteria,
grow specifically in tumor tissues. This specificity is attributed to the
following: (1) Vascular walls in tumor tissues have nanometer- to micrometer-wide
cracks, which allow the bacteria to pass through; (2) the intratumoral
environment is hypoxic, due to poor vascularization, and therefore bifidobacteria
can survive and proliferate in this anaerobic environment; (3) bifidobacteria
cannot survive in well-oxygenated normal tissues. Moreover, unlike gram-negative
bacteria, the gram-positive bifidobacteria do not produce endotoxins; therefore,
there is no risk of endotoxin shock associated with their intravenous
administration. Recently, the utility of bifidobacteria for specific drug
delivery to tumor tissues has been highlighted. We have established a novel anti
cancer drug-delivery system using Bifidobacterium longum for the specific release
of anti-tumor antibodies (e.g., antibody-drug complexes or single-chain
antibodies) to targeted tumor tissues. Here, we introduce the results of our
investigation.
PMID- 29962471
TI - [Various Physiological Actions Mediated through a Na+/Glucose Co-transporter
(SGLT) and the Possibility of the Innovative Drug Development].
PMID- 29962472
TI - [Sodium-Glucose Transporters as a Therapeutic Target for Diabetes from the
Viewpoint of Drug Discovery and Pharmacotherapy].
AB - Sodium-glucose transporter (SGLT)-2 inhibitors, which are currently in clinical
use in most of the world, are unique as their hypoglycemic effects are completely
independent of insulin action. Potential benefits and indications for the
treatment of other diseases like circulatory and renal disorders are attracting
attention. SGLT2 inhibitors not only reduce blood glucose levels but also alter
the whole-body energy balance to lower body weight, which should result in the
amelioration of multiple metabolic disorders like metabolic syndrome. In the
symposium, we briefly introduced the physiological as well as biological
functions of SGLTs and discussed strategies for drug design by looking back at
the history of drug discovery for SGLT2 inhibitors. We also shared our recent
data on their combined usage with other hypoglycemic agents and effects on
glucagon secretion, which are current clinical topics relevant to SGLT2
inhibitors. Among those topics, strategies for drug discovery of SGLT2 inhibitors
are discussed in this review.
PMID- 29962473
TI - [Roles of Sodium-Glucose Cotransporter 1 (SGLT1) in the Induction of Cardiac
Remodeling].
AB - It is well-known that metabolic remodeling occurs in the presence of
cardiomyopathy induced by cardiac ischemia and hypertrophy, and diabetes
mellitus. It is also known that a novel cardiac glucose transporter, sodium
glucose co-transporter 1 (SGLT1), is expressed in the human heart. However, the
role of SGLT1 in the development of cardiac metabolic remodeling is still
unclear. Recent studies demonstrated that SGLT1 activation improves ischemia
reperfusion-induced cardiac injury, and increased SGLT1 gene expression is
observed in hypertrophic, ischemic, and diabetic cardiomyopathy in human hearts.
Moreover, increases in SGLT1 protein expression cause cardiac remodeling such as
hypertrophy and increased interstitial fibrosis in mice. We demonstrated that
ischemia-reperfusion-induced cardiac injury was potentiated in SGLT1-deficient
mice. In contrast, chronic pressure overload induced by transverse aortic
constriction (TAC) caused cardiac hypertrophy and reduced left ventricular
fractional shortening in C57BL/6J wild-type mice. Moreover, the TAC-induced
hypertrophied heart showed increased SGLT1 and AMPKalphaprotein expressions.
These results suggest the different effects of SGLT1 activation on cardiac
diseases such as acute ischemia-reperfusion-induced cardiac injury and
chronically-induced cardiac hypertrophy. Thus, SGLT1 may be a novel therapeutic
target for the treatment of patients with cardiac diseases such as ischemic and
hypertrophic cardiomyopathy.
PMID- 29962474
TI - [Dapagliflozin, a Sodium-Glucose Co-transporter-2 Inhibitor, Acutely Reduces
Energy Expenditure in Brown Adipose Tissue via Neural Signals in Mice].
AB - Selective sodium glucose transporter-2 inhibitor (SGLT2i) treatment promotes
urinary glucose excretion, thereby reducing blood glucose as well as body weight.
However, only limited body weight reductions are achieved with SGLT2i
administration. Hyperphagia is reportedly one of the causes of this limited
weight loss. However, the effects of SGLT2i on systemic energy expenditure have
not been fully elucidated. We investigated the acute effects of dapagliflozin, an
SGLT2i, on systemic energy expenditure in mice. Eighteen hours after
dapagliflozin administration, oxygen consumption and brown adipose tissue (BAT)
expression of ucp1, a thermogenesis-related gene, were significantly decreased as
compared with those after vehicle administration. In addition, dapagliflozin
significantly suppressed norepinephrine (NE) turnover in BAT and c-fos expression
in the rostral raphe pallidus nucleus (rRPa), which contains the sympathetic
premotor neurons responsible for thermogenesis. These findings indicate that the
dapagliflozin-mediated acute decrease in energy expenditure involves a reduction
in BAT thermogenesis via decreased sympathetic nerve activity from the rRPa.
Furthermore, common hepatic branch vagotomy abolished the reductions in ucp1
expression, NE contents in BAT, and c-fos expression in the rRPa. In addition,
alterations in hepatic carbohydrate metabolism, such as decreases in glycogen
contents and upregulation of phosphoenolpyruvate carboxykinase, occurred prior to
the suppression of BAT thermogenesis, e.g., 6 h after dapagliflozin treatment.
Collectively, these results suggest that SGLT2i acutely suppresses energy
expenditure in BAT via regulation of an interorgan neural network consisting of
the common hepatic vagal branch and sympathetic nerves.
PMID- 29962475
TI - [Potential of the Cerebral Sodium-Glucose Transporter as a Novel Therapeutic
Target in Cerebral Ischemia].
AB - Cerebral ischemic stress often induces a hyperglycemic condition. This
postischemic hyperglycemia exacerbates the development of cerebral ischemic
neuronal damage, although the mechanism of this exacerbation remains to be
clarified. We previously discovered that the cerebral sodium-glucose transporter
(SGLT) was closely involved in the development of cerebral ischemic neuronal
damage. SGLT is a member of the glucose transporter family and moves glucose
together with sodium ions. SGLT-1, -3, -4, and -6 are distributed in the brain.
We conducted further experiments to elucidate the detailed mechanism of the
exacerbation of cerebral ischemia by cerebral SGLT. The results clarified: 1) the
relationship between cerebral SGLT and postischemic hyperglycemia; 2) the
involvement of cerebral SGLT-1 (a cerebral SGLT isoform) in cerebral ischemic
neuronal damage; and 3) the effects of sodium influx through cerebral SGLT on the
development of cerebral ischemic neuronal damage. This paper presents our data on
the involvement of cerebral SGLT in the exacerbation of cerebral ischemic
neuronal damage.
PMID- 29962476
TI - [Effect of Non-alcoholic Beverage Intake in Children on Alcoholic Beverage
Drinking and Smoking].
AB - The early intake of alcohol and/or nicotine in childhood or adolescence is one
of risk factors for alcohol and/or nicotine dependence in adult. Recently, non
alcoholic beverages with less than 0.00% alcohol are on sale for adults as
substitutes for alcoholic beverages without strict legal limitations. However, it
is unclear whether non-alcoholic beverages could be a risk factor in drinking and
smoking in childhood or adolescence. The purpose of the present survey is to
clarify the effect of non-alcoholic beverage intake in children on alcoholic
beverage drinking and smoking. We examined as follows: the experience of
alcoholic or non-alcoholic beverage intake, and of smoking in elementary school
pupils and/or their family members, and interest in or motivation for drinking
and smoking in the pupils. As a result, the percentage of alcoholic or non
alcoholic beverage intake, and of smoking in the pupils were 16.8% or 21.9%, and
0.3%, respectively. The number of family members took the alcoholic or non
alcoholic beverage was larger in the pupils took it compared to the pupils did
not take it. In the pupils who experienced the non-alcoholic beverage intake,
interest in or motivation for drinking alcoholic beverages and/or smoking is
higher than in those who did not. These findings indicate that non-alcoholic
beverage intake is related to drinking and smoking. We will introduce drug abuse
prevention education on the risk of drug dependence among childhood or
adolescents based on the findings of this survey.
PMID- 29962477
TI - [Comparison of Chemical Behavior of Original and Generic Docetaxel Formulations
as Non-alcoholic Preparations: Discussion about Diluent Solvents for Docetaxel].
AB - Although generic anti-tumor agents are in wide clinical use, they have not in
all cases been shown to be equivalent to the original agents after preparation.
In the present study, original and generic docetaxel formulations were compared
with respect to stability when prepared as a non-alcoholic solution for use. When
the original formulation was diluted with physiological saline solution to make a
non-alcoholic preparation, the concentration decreased with time, whereas no such
decrease occurred when a preparation of the generic formulation was made in a
similar manner. With both the original and generic formulations, no decrease in
docetaxel concentration with time was found after dilution with 5% glucose
solution. On the basis of these results, it is concluded that the behaviors of
original and generic docetaxel formulations are not equivalent when prepared, but
that the original and generic formulations can be taken to be equivalent if they
are diluted with 5% glucose solution at preparation.
PMID- 29962478
TI - [Assessment of the Relationship between Hypnotics and Delirium Using the Japanese
Adverse Drug Event Report (JADER) Database].
AB - The Japanese Adverse Drug Event Report (JADER) database was used to examine the
risk of delirium and the time of its onset with various hypnotics, including 10
benzodiazepines (BZDs), 3 non-benzodiazepines (non-BZDs), 1 melatonin receptor
agonist (MRTA), and 1 orexin receptor inhibitor (OXRI). Data entered in the JADER
database between April 1, 2004 and February 1, 2016 were analyzed. The index for
safety signal detection, the reporting odds ratio (ROR), was the odds ratio for
adverse drug reaction reporting. The ROR for each drug was calculated; a signal
was considered present if the lower bound of the 95% confidence interval of the
ROR was greater than 1. The time to onset of delirium was calculated for drugs
for which the number of days from the start of drug administration to delirium
onset was reported. During the period examined in the analysis, a total of 621114
adverse drug reaction reports were seen, and the total number of delirium reports
was 1417 after redundant cases were excluded. A signal was detected for 5 of the
10 BZDs and all 3 non-BZDs, with no signal for the MRTA and the OXRI. The time of
delirium onset varied widely even for drugs classified as being in the same
action duration group, and no correlation was seen for delirium onset time. The
results of this study suggested that delirium risk varies depending on the
hypnotic. Thus, hypnotics can be selected according to their delirium risk.
PMID- 29962479
TI - [Survey of the Distribution of Community Pharmacists Using Government
Statistics].
AB - In Japan, within the background of a progressively aging society, a community
general support system is gradually being established. Under this system,
community pharmacists are expected to expand their activities in local
communities. Here, we surveyed the distribution of community pharmacists in Japan
by using government statistics. We found that there are 153 towns/villages
without community pharmacists, which is about six times the number of towns
without physicians (26 towns/villages). The number of community pharmacists per
100000 population was correlated with the population of the municipality. There
was a significant difference in the number of community pharmacists per 100000
population between depopulated and non-depopulated areas. A multiple regression
analysis revealed that population, financial capability index, and number of
physicians per 100000 population were positively associated with the number of
community pharmacists per 100000 population in a given municipality. We hope that
the survey provides useful information about future issues facing community
pharmacy in a community general support system.
PMID- 29962480
TI - A Safety and Immunogenicity Study of a Single Dose of a Meningococcal (Groups A,
C, W, and Y) Polysaccharide Diphtheria Toxoid Conjugate Vaccine (MEN-ACWY-D) in
Healthy Japanese Participants.
AB - Meningococcal disease can cause significant disability and mortality. The
quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine
(Men-ACWY-D) protects against invasive meningococcal disease caused by serogroups
A, C, W, and Y. This phase III, open-label, single-arm, multicenter study
evaluated the safety and immunogenicity of a single vaccine dose in healthy
Japanese adults. The study enrolled 200 participants between 2 and 55 years of
age. Immunogenicity was assessed by quantifying the seroprotection rates (the
proportion of participants with antibody titers >= 1:128 against the capsular
polysaccharide from all 4 serogroups measured 28 days after vaccination). Safety
endpoints included occurrence, nature, time to onset, duration, intensity,
relationship to vaccination, and outcome of solicited and unsolicited adverse
events (AEs) and serious AEs (SAEs). Participants included 194 adults, 2
adolescents, and 4 children. Among adults, the seroprotection rates for
serogroups A, C, W, and Y were 91.2%, 80.2%, 89.1%, and 93.8%, respectively.
Seroconversion rates (the proportion of participants with pre-vaccination titers
of < 1:4 and a >= 4-fold rise from baseline) were 87.3%, 83.0%, 94.4%, and 96.4%,
respectively. No immediate AEs, adverse reactions, SAEs, or deaths were reported
for any age group. Men-ACWY-D is well tolerated and immunogenic, eliciting
antibodies against capsular polysaccharides from all 4 serogroups in Japanese
adults.
PMID- 29962481
TI - A Case of Conjunctival Ulcer and Uveitis Caused by Acrophialophora Sp. in an
Immunocompromised Patient: a Case Report and Riterature Review.
AB - We report the first case of invasive ophthalmologic infection by Acrophialophora
sp. that was successfully treated using voriconazole (VRCZ). Acrophialophora
spp., which has been reported to be an opportunistic pathogen, is a rare
thermotolerant soil fungus, but its pathogenicity remains unclear. A 77-year-old
man had neutropenia and prostate carcinoma and was receiving hemodialysis. His
right eye had been infected for 2 days. His conjunctiva was congested, and it
partially formed an abscess. Liposomal amphotericin B (L-AMB) was administered
following systemic itraconazole. However, the treatment was changed from L-AMB to
systemic VRCZ and VRCZ eye drops because his eye symptoms worsened. Subsequently,
his symptoms stabilized and his vision was maintained. Acrophialophora sp. was
identified by analyzing regions of internal transcribed spacer and domain 1 and 2
of the ribosomal RNA gene. He completed the 7-week systemic VRCZ course. The mean
minimum inhibitory concentration of VRCZ for Acrophialophora spp. has been
reported to be the lowest among various antifungal agents, and our results
indicated the efficacy of VRCZ treatment for Acrophialophora sp. infection. Our
results suggest that invasive Acrophialophora sp. infection may require long-term
therapy. Further analysis of the clinical spectrum of Acrophialophora spp.
infection and adequate treatment methods are required in the future.
PMID- 29962482
TI - Bartonella henselae Neuroretinitis in Patients without Cat Scratch.
AB - Cat scratch disease (CSD) is a syndrome characterized by lymphadenopathy, fever,
and skin lesions following a cat scratch or bite. Bartonella henselae is the
primary bacterial agent responsible for CSD. In this report, we describe cases
with atypical presentation of serologically proven B. henselae neuroretinitis. In
this study, 3 patients with neuroretinitis were evaluated. Animal contact
histories; results of ocular examinations and systemic investigations; clinical
findings; and treatment compliance of the patients were assessed. All patients
denied history of contact with cats or other animals, and they did not have CSD
findings. Serologic testing via indirect immunofluorescence assay (IFA) was used
to diagnose Bartonella neuroretinitis. The IFA test results were positive for all
patients. Two patients were treated with antibiotics. Optic disc edema and
macular exudates resolved gradually, and at their last follow-up visits, all
signs had disappeared. There was no disease recurrence after the completion of
treatment. Serious complications were seen in the untreated patient. In
conclusion, B. henselae infection should be considered even when there are no
systemic signs and symptoms of CSD in patients with neuroretinitis.
PMID- 29962483
TI - Identification of Three Distinct Groups of Anopheles lindesayi in Japan by
Morphological and Genetic Analyses.
AB - Anopheles (Anopheles) lindesayi Giles consists of 5 subspecies. In Japan, only
one subspecies, An. l. japonicus Yamada, has been reported. Its geographical
populations are morphologically diverse; however, they are regarded as a single
subspecies. In this study, we re-evaluated the taxonomic status of An. l.
japonicus in Japan, and that of another subspecies, An. l. pleccau, distributed
in Taiwan, by comparative morphological and molecular analyses based on the gene
sequences of mitochondrial DNA cytochrome c oxidase I (COI) and ribosomal DNA
internal transcribed spacer 2 (ITS2). Nucleotide sequence divergence was
calculated using the Kimura-two-parameter (K2P) distance model. Phylogenetic
trees based on COI and ITS2 sequences showed 3 distinct clades: Eastern Japan,
Western Japan, and the Ryukyus. The sequences of the Ryukyu specimens were
located within the same clade as that of the sequences of the Taiwanese
specimens. Regarding the COI sequences, the 3 geographical groups in Japan were
genetically distinct. The following morphological characteristics distinguished
the groups: larval seta 1-S, pupal setae 5 through segments IV-VII, and pupal
setae 6 on segments IV-VII. Based on these results, it was revealed that An. l.
japonicus included 3 genetically and morphologically distinct groups: 2 groups of
An. l. japonicus and a group in the Ryukyus, which was a synonym of An. l.
pleccau.
PMID- 29962484
TI - International Travel and Exotic Dengue Fever in South Korea from 2006 to 2015.
AB - We analyzed reported dengue fever (DF) cases and DF-relevant characteristics in
South Korea from 2006 to 2015. A total of 1,260 DF notifications were obtained
during the study period that were presumably introduced from endemic foreign
countries. The nationwide cumulative incidence rate (CIR) of DF was 0.25 per
100,000 population; CIR of DF among overseas travelers was 0.93. CIRs of overseas
male and female travelers were 1.13 and 0.87, respectively. CIR of overseas
travelers aged 20-39 years was the highest. More men (61.9%) were infected with
the dengue virus than women (38.1%, P<0.01). Individuals aged 20-39 years were
most infected than those of other ages (58.4%, P<0.01). About a third of reported
DF cases occurred between June and November. Most of the imported DF cases were
associated with traveling in Southeast Asia (86.1%). The incidence of DF was
highly correlated with the total number of overseas travelers (Pearson
correlation r=0.842, P<0.01). The number of reported patients with DF has been
increasing in the last decade, and DF is associated with international travel. To
prevent dengue virus infections, greater attention should be paid to individuals
who are planning to travel to Southeast Asia.
PMID- 29962485
TI - Epidemiological Outbreaks of Measles Virus in Kazakhstan during 2015.
AB - This study involved epidemiological surveillance of the measles virus (MV) in the
territory of the Republic of Kazakhstan during 2015-2016. We detected MV genotype
D8 in this season of measles outbreak. A total of 2,341 cases were registered and
19 were identified by genotyping. Sixteen of these samples were attributed to
subgroup A of genotype D8, while 3 imported cases were represented by genotypes
B3 and H1. Analysis of vaccination coverage showed that a large group of infected
people were not vaccinated or did not have a reliable report on their vaccination
status. This issue might increase the morbidity rate among the healthy population
in outbreak seasons. To prevent the incidence caused by this problem, we have
successfully introduced epidemiologic measures for the control of measles.
PMID- 29962486
TI - Cutaneous Findings of Crimean-Congo Hemorrhagic Fever: a Study of 269 Cases.
AB - Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease. We aimed to
investigate the cutaneous manifestations of CCHF and reveal their associations
with fatality. Two hundred and sixty-nine patients diagnosed with CCHF were
assessed. Skin findings were observed in 170 (63.2%) patients. A facial rash was
the most common cutaneous finding (n = 82, 30.5%). In severe cases, hemorrhagic
cutaneous manifestations (petechiae and ecchymoses) were recognized. A
statistically significant correlation was obtained between cutaneous
manifestations and fatality, and it was determined that there was a strong
positive correlation between fatality and ecchymosis (r = 567, p < 0.001). In
addition, a logistic regression analysis was performed, and death occurred 4.69
times more in those with skin signs than in those without. We hypothesize that
CCHF patients with ecchymosis are at the highest risk and that cutaneous findings
can contribute to the prognosis of CCHF.
PMID- 29962487
TI - Epidemiology Characteristics of Human Coxsackievirus A16 and Enterovirus 71
Circulating in Linyi, China, from 2009 to 2017.
AB - In China, a rapid expansion of hand, foot, and mouth disease (HFMD) outbreaks has
occurred since 2004, and HFMD has become an important issue in China. There are
more than 20 types of enterovirus causing HFMD, of which coxsackievirus A16
(CA16) and enterovirus 71 (EV71) are the most common. This study aimed to analyze
the epidemiological characteristics of HFMD caused by EV71 and CA16 in Linyi,
Shandong province, China, from 2009 to 2017. The stool specimens and throat
samples of 5,324 patients with HFMD were obtained for nucleic acid detection of
enterovirus. A total of 4,040 HFMD cases were caused by viral pathogens. Of
these, 1,706 cases were positive for EV71 and 1,266 were positive for CA16. These
2 virus strains appeared alternately in Linyi city. The incidence of EV71
positive and CA16-positive cases was highest in children aged 0-5 years, with
male patients being predominant. This outbreak of HMFD caused by EV71 and CA16
mainly occurred between April and July and appeared alternately between the years
2011 and 2017. These results demonstrated that the epidemiological analysis of
EV71 and CA16 can provide a scientific basis for the prevention and treatment of
the disease.
PMID- 29962488
TI - The Largest Measles Outbreak, Including 38 Modified Measles and 22 Typical
Measles Cases in Its Elimination Era in Yamagata, Japan, 2017.
AB - The incidence of modified measles (M-Me), characterized by milder symptoms than
those of typical measles (T-Me), has been increasing in Japan. However, the
outbreak dominated by M-Me cases has not been thoroughly investigated worldwide.
The largest importation-related outbreak of measles with genotype D8 occurred in
Yamagata Prefecture, Japan, from March to April 2017. This phenomenon was
observed after Japan had achieved measles elimination in 2015. We confirmed 60
cases by detecting the genome of the measles virus (MeV). Among the cases, 38
were M-Me and 22 were T-Me. Thirty-nine (65.0%) patients were 20-39 years of age.
Three out of 7 primary cases produced 50 transmissions, of which each patient
caused 9-25 transmissions. These patients were 22-31 years old and were not
vaccinated. Moreover, they developed T-Me and kept contact with the public during
their symptomatic periods. Considering that M-Me is generally caused by vaccine
failure, some individuals in Japan may have insufficient immunity for MeV.
Accordingly, additional doses of measles vaccine may be necessary in preventing
measles importation and endemicity among individuals aged 20-39 years.
Furthermore, to accurately and promptly diagnose individuals with measles,
particularly those who can be considered as primary cases, efforts must be
exerted to detect all measles cases using epidemiological and genetic approaches
in countries where measles elimination had been achieved.
PMID- 29962490
TI - Human Papillomavirus Genotypes and HPV16 E6/E7 Variants among Patients with
Genital Cancers in Vietnam.
AB - We previously reported human papillomavirus type 52 (HPV52) as the most prevalent
high-risk genotype in non-cancer individuals in Vietnam. This study aimed to
evaluate HPV genotypes and HPV16 E6 and E7 (E6/E7) gene variations in Vietnamese
patients with genital cancers. Biopsy samples were collected from 124 Vietnamese
patients with genital cancers (20 with vaginal, 50 with vulvar, and 54 with
penile cancer). The HPV-DNA was amplified and genotyped, and HPV16 E6/E7 genes
were compared with those previously reported for women with normal cervical
cytology (N = 23). HPV-DNA was detected in 80.6% (100/124) of the cancer patients
(80.0% of vaginal, 82.0% of vulvar, and 79.6% of penile), with HPV16/18 in 86.0%
(86/100) and HPV52 in 7.0% (7/100) of the HPV-positive samples. The HPV-DNA
prevalence and HPV genotype distribution did not significantly differ among the
genital cancer patients (both P = 0.95). Significantly fewer instances of the
HPV16 A4 sublineage (34.8% vs. 82.6%, P < 0.0001) and HPV16 E7 29S (36.4% vs.
87.0%, P = 0.0002) occurred in the cancer patients than in the women with normal
cytology. Our results indicate that HPV16/18 accounts for more than 85% of
genital cancers in Vietnam, and the HPV16 sublineage A4 containing E7 29S may be
less oncogenic.
PMID- 29962491
TI - Association of Low Family Income With Lung Function Among Children and
Adolescents: Results of the J-SHINE Study.
AB - BACKGROUND: The respiratory tract of children in low-income families is more
likely to be exposed to toxins, which may lead to poor lung function. The purpose
of this study was to elucidate the impact of low household income on lung
function among children and adolescents in Japan. METHODS: We analyzed a
population-based sample of 1,224 children aged 5 to 17 years old from the
Japanese Study on Stratification, Health, Income, and Neighborhood (J-SHINE).
Forced expiratory volume in 1 s (FEV1) and in 6 s (FEV6) was measured. Annual
household income and other potential covariates were assessed through a
questionnaire. Low household income was defined as less than 3 million yen
(approximately 27,000 United States dollars [USD]) per year. Multivariate
regression analysis was used to adjust for potential covariates. RESULTS: We
observed statistically significantly lower FEV1:FEV6 ratio with children in
lowest-income families compared with those in highest-income families, after
adjusting for child's age and sex (coefficient = -0.082; 95% confidence interval
[CI], -0.131 to -0.034). After adjusting for other covariates, including parental
smoking status and parental diagnosis of asthma, a similar trend remained
(coefficient = -0.054; 95% CI, -0.109 to 0.001). CONCLUSIONS: Children in low
income families showed significantly lower lung function than those in high
income families. Prevention and early intervention are necessary to help the
development of lung function among children living in low-income families.
PMID- 29962489
TI - Comparison of Neutralizing Antibody Titers against Japanese Encephalitis Virus
Genotype V Strain with Those against Genotype I and III Strains in the Sera of
Japanese Encephalitis Patients in Japan in 2016.
AB - Japanese encephalitis (JE) is an acute viral disease caused by the Japanese
encephalitis virus (JEV). JEV strains are classified into 5 genotypes (I-V). JEV
genotype V strains have never been detected in Japan to date, but they were
recently detected in South Korea. In the present analysis, we tried to determine
if a JEV genotype V strain caused any JE case in Japan in 2016. Serum and
cerebrospinal fluid samples were collected from 10 JE patients reported in Japan
in 2016. JEV RNA was not detected in any of the samples. Although JEV is a single
serotype virus, it can be expected that the neutralizing antibody titers against
JEV genotype V strains are higher than those against genotype I and III strains
in the serum of patients with JE in Japan whose causative JEV was the genotype V
strain. The neutralizing antibody titers against the JEV genotype V strain were
not higher than those against the genotype I or III strain in any serum samples.
Therefore, the evidence that the JEV genotype V strain caused any JE case in
Japan in 2016 was absent.
PMID- 29962492
TI - A Community-Wide Intervention Trial for Preventing and Reducing Frailty Among
Older Adults Living in Metropolitan Areas: Design and Baseline Survey for a Study
Integrating Participatory Action Research With a Cluster Trial.
AB - BACKGROUND: Preventing and reducing frailty is an important challenge for Japan
in the next decade, especially in metropolitan areas. We launched a community
wide intervention trial (the Ota Genki Senior Project) in 2016 to develop
effective community-based strategies for frailty prevention in metropolitan
areas. This report describes the study design and baseline survey. METHODS: This
study is a community-wide intervention trial that integrates participatory action
research into a cluster non-randomized controlled trial for adults aged 65 years
or older living in Ota City, Tokyo. We allocated 3 of 18 districts to an
intervention group and the other 15 to a control group. Using a mailed self
administered questionnaire, we conducted a baseline survey of 15,500 residents
(8,000 and 7,500 in the intervention and control groups, respectively) from July
through August 2016. In addition to socioeconomic status and lifestyle variables,
we assessed frailty status (primary outcome) and physical, nutritional, and
psychosocial variables (secondary outcomes). Based on the baseline findings, an
intervention to improve outcomes will be implemented as participatory action
research. Follow-up surveys will be conducted in the same manner as the baseline
survey. RESULTS: A total of 11,925 questionnaires were returned (76.9% response
rate; 6,105 [76.3%] and 5,820 [77.6%] in the intervention and control groups,
respectively), and 11,701 were included in the analysis (mean age, 74.3 [standard
deviation, 5.5] years; 48.5% were men). CONCLUSIONS: This study is expected to
contribute to development of a prototype of a community-wide frailty prevention
strategy, especially in metropolitan areas in Japan. TRIAL REGISTRATION: UMIN
Clinical Trials Registry (UMIN000026515).
PMID- 29962493
TI - Physical Activity and Health-Related Quality of Life Among Low-Income Adults in
Metropolitan Kuala Lumpur.
AB - BACKGROUND: The aim of this research is to assess the level of physical activity
(PA) in relation to different socio-economic factors and to examine the effect of
the recommended level of PA on the domains of quality of life (QoL) among
residents of low-income housing in the metropolitan area of Kuala Lumpur,
Malaysia. METHODS: This was a cross-sectional study that included 680 respondents
from community housing projects. Reported PA was assessed using the Global
Physical Activity Questionnaire (GPAQ) short form version 2. The SF-12v2 was
administered to assess the health-related QoL (HRQoL) among the study population.
Respondents were grouped into "active" and "insufficient" groups according to
reported weekly PA level. One-way analysis of variance, analysis of co-variance,
and multiple linear regression were used in the analysis. RESULTS: Overall, 17.6%
(95% CI, 14.3-20.9) of the respondents did not achieve the recommended levels of
PA (>=600 metabolic equivalent [MET]-minutes week-1). Level of achieving
recommended PA was higher among younger participants, females, members belonging
to nuclear families, and in self-employed participants. The group that fulfilled
recommended PA levels (active) has higher levels of QoL in all domains except
physical functioning. CONCLUSIONS: Almost one out of five low-income urban
residents were physically inactive. In addition, individuals who attained
recommended PA levels had better scores on some domains of HRQOL than those who
did not. Our findings call for tailor-made public health interventions to improve
PA levels among the general population and particularly for low-income residents.
PMID- 29962494
TI - The utilization of phototherapy in the department of dermatology, Hospital Kuala
Lumpur: A 5-year audit.
AB - INTRODUCTION: Ultraviolet phototherapies are important treatment modalities for a
wide range of dermatological conditions. We aim to describe the utilization of
phototherapy in the Department of Dermatology Hospital Kuala Lumpur. METHODS:
This is a 5-year retrospective audit on patients who underwent phototherapy
between 2011 and 2015. RESULTS: There were 892 patients, M:F=1.08:1, aged from 4-
88 years, with a median age of 38.8 years who underwent phototherapy. Majority
(58.9%) had skin phototype IV, followed by type III (37.7%) and type II (0.7%).
There were 697(78.1%) who underwent NBUVB, 136 (15.2%) had topical PUVA, 22(2.5%)
had oral PUVA, 12(1.4%) had UVA1 and 23(2.6%) had NBUVB with topical or oral
PUVA/UVA1 at different time periods. The indications were psoriasis (46.6%),
vitiligo (26.7%), atopic eczema (9.8%), pityriasis lichenoides chronica (5.3%),
mycosis fungoides (3.9%), lichen planus (2.5%), nodular prurigo (2.2%),
scleroderma (1.2%), alopecia areata (0.7%) and others. The median number of
session received were 27 (range 1-252) for NBUVB, 30 (range 1-330) for topical
PUVA, 30 (range 3-190) for oral PUVA and 24.5 (range 2-161) for UVA1. The acute
adverse effects experienced by patients were erythema (18%), pruritus (16.3%),
warmth (3.3%), blister formation (3.1%), cutaneous pain (2.4%), and xerosis
(0.8%), skin swelling (0.7%) and phototoxicity (0.2%). CONCLUSION: Narrow-band
UVB was the most frequently prescribed phototherapy modality in our center. The
most common indication for phototherapy in our setting was psoriasis. Acute
adverse events occurred in a third of patients, although these side effects were
mild.
PMID- 29962495
TI - Anatomic variants and anomalies of coronary arteries detected by computed
tomography angiography in southern Thailand.
AB - OBJECTIVE: To evaluate the prevalence of coronary artery anatomic variants and
anomalies detected by computed tomography angiography (CTA) MATERIALS AND
METHODS: A retrospective study was conducted on all patients undergoing coronary
CTA using a 64-detector row CT in the Radiology Department, Songklanagarind
Hospital, from January 2010 to January 2013. Data were recorded and analyzed.
RESULTS: The imaging results of 279 patients were reviewed. One hundred and
twenty-two females (43.7%) and 157 males (56.3%) [age range, 26-82 years] were
reviewed for coronary artery variants and anomalies with post-processing images.
The right coronary dominance was the most common dominant type (91.4%). The
prevalence of ramus intermedius was 68.8%; those of the absence of the left main
coronary artery and left circumflex artery were 0.4%, respectively; and of the
high takeoff of the coronary artery was 3.6%. Anomalies of origin and course were
detected as the right coronary artery originating from the left coronary sinus in
1.1% of the patients. Myocardial bridging and coronary fistulas were demonstrated
in 55.6% and 0.7% of our subjects, respectively. CONCLUSION: A coronary CTA can
effectively represent the complex anatomy of the coronaries as well as their
anatomic variations and anomalies. The prevalence of most coronary variations
were in concordance with the data of previous reports.
PMID- 29962496
TI - Hepatitis B virus infection among children of hepatitis B surface antigen
positive mothers in a Malaysian hospital.
AB - INTRODUCTION: There have been no published data on the transmission of hepatitis
B virus (HBV) infection among children of hepatitis B surface antigen (HBsAg)
positive mothers in Malaysia. METHODS: This is a cross-sectional study of all the
children of HBsAg-positive mothers who delivered at the University of Malaya
Medical Centre between 1993 and 2000. RESULTS: A total of 60 HBsAg-positive
mothers and their 154 children participated in the study. HBsAg was detected in
four children (2.6%) while IgG antibody to the hepatitis B core antigen (anti-HBc
IgG) was detected in seventeen children (11.0%). The mother's age at childbirth
was significantly lower in the children with detectable HBsAg (22.5+/-6.1 years
vs. 29.7+/-4.5 years, p=0.043) and anti-HBc IgG (26.6+/-6.1 years vs. 30.0+/-4.3
years, p=0.004). Children born in the 1980s were significantly more likely to
have detectable HBsAg (18.8% vs. 0.7%, p=0.004) and anti-HBc IgG (37.5% vs. 8.0%,
p=0.000) compared with those born later. All children with detectable HBsAg were
born via spontaneous vaginal delivery, and hepatitis B immunoglobulin was either
not given or the administration status was unknown. The majority of mothers with
chronic HBV infection (70.4%) were not under any regular follow-up for their
chronic HBV infection and the main reason was the lack of awareness of the need
to do so (47.4%). CONCLUSION: Transmission of HBV infection among children of
HBsAg-positive mothers in Malaysia is low. However, attention needs to be given
to the high rate of HBsAgpositive mothers who are not on any regular follow-up.
PMID- 29962497
TI - The role of PET/CT amyloid Imaging compared with Tc99m-HMPAO SPECT imaging for
diagnosing Alzheimer's disease.
AB - BACKGROUND: Imaging such as Tc99m-HMPAO single photon emission computed
tomography (SPECT), and positron emission tomography/ computed tomography
(PET/CT) amyloid scans are used to aid the diagnosis of Alzheimer's disease (AD).
OBJECTIVE: We aimed to correlate the ability of these modalities to differentiate
Probable AD and Possible AD using the clinical diagnosis as a gold standard. We
also investigated the correlation of severity of amyloid deposit in the brain
with the diagnosis of AD. METHODS: A retrospective study of 47 subjects (17
Probable AD and 30 Possible AD) who were referred for PET/CT amyloid scans to our
centre was conducted. Hypoperfusion in the temporo-parietal lobes on Tc99m-HMPAO
SPECT and loss of grey-white matter contrast in cortical regions on PET/CT
Amyloid scans indicating the presence of amyloid beta deposit were qualitatively
interpreted as positive for AD. SPECT and PET/CT were also read in combination
(Combo reading). The severity of amyloid beta deposit was semiquantitatively
assessed in a visual binary method using a scale of Grade 0-4. The severity of
amyloid beta deposit was assessed in a visual binary method and a semi
quantitative method using a scale of Grade 0-4. RESULTS: There was significant
correlation of Tc99m-HMPAO SPECT, PET/CT amyloid findings and Combo reading with
AD. The sensitivity, specificity, PPV and NPV were 87.5%, 73.7%, 58.3% and 93.3%
(SPECT); 62.5%, 77.4%, 58.8% and 80.0% (PET/CT) and 87.5%, 84.2%, 70.0% and 30.0%
(Combo reading) respectively. The grade of amyloid deposition was not
significantly correlated with AD (Spearman's correlation, p=0.687). CONCLUSION:
There is an incremental benefit in utilizing PET/CT amyloid imaging in cases with
atypical presentation and indeterminate findings on conventional imaging of
Alzheimer's disease.
PMID- 29962498
TI - Incidence of vaginal erosion with different synthetic materials for suburethral
sling in the treatment of Stress Urinary Incontinence: A systematic review.
AB - INTRODUCTION: The aim of this systematic review is to compare the vaginal erosion
rates in different synthetic materials used in suburethral slings in Tension Free
Vaginal Tape (TVT-O /TOT) procedures in management of female stress urinary
incontinence. METHODS: PRISMA 2009 framework was adopted for study design.
Scholarly literature search was done using MEDLINE, EMBASE, the Cochrane Library
and Clinical Trials.gov using selected keywords. Five articles fulfilled the
inclusion and exclusion criteria. Our main outcome of interest is to review the
ideal properties of the suburethral sling, procedure of insertion and post
surgical complication following the sling insertion primarily vaginal erosion.
Results were compared using one way-ANOVA test and independent T- test. RESULTS:
Total of 1725 subjects were available for analysis in the five studies.
Monofilament polypropylene constituted 92.5% of the total sample size from one
study alone. Polyester (n= 16/51) causes higher incidence rate of vaginal erosion
compared to monofilament polypropylene (31.4 vs., 4.7; p = 0.01). There was no
difference in the vaginal erosion rate between monofilament polypropylene and
multifilament polypropylene (4.7 vs, 14.1; p=0.055) as well as between
multifilament polypropylene and polyester (14.1 vs, 31.4; p=0.068). Although
there was a marginally lower rate of vaginal erosion in TVT-O over TVT, the
difference was not significant. (5.6 vs., 6.4, p=0.468). Common presentations of
vaginal erosion were vaginal discharge, perineal pain and dyspareunia.
CONCLUSION: Given the limited sample size, polyester sling material appears to
cause higher rates of vaginal erosion. No difference in erosion rate was seen
between TVT and TVT-O.
PMID- 29962499
TI - Updates in the management of Dyslipidaemia in the high and very high risk
individual for CV risk reduction.
AB - Cardiovascular disease (CVD) has been the main cause of mortality and an
important cause of morbidity in Malaysia for several years. To reduce global
cardiovascular (CV) risk in the population, primary preventive strategies need to
be implemented. Hypercholesterolaemia is one of the major risk factors for CVD.
This paper is an expert review on the management of hypercholesterolemia focusing
on high and very high risk individuals. In low and Intermediate risk individuals,
therapeutic lifestyle changes (TLC) and a healthy lifestyle alone may suffice. In
high and very high risk individuals, drug therapy in conjunction with TLC are
necessary to achieve the target LDL-C levels which have been shown to slow down
progression and sometimes even result in regression of atherosclerotic plaques.
Statins are first-line drugs because they have been shown in numerous randomized
controlled trials to be effective in reducing CV events and to be safe. In some
high risk individuals, despite maximally tolerated statin therapy, target Low
Density Lipoprotein Cholesterol (LDL-C) levels are not achieved. These include
those with familial hypercholesterolaemia and statin intolerance. This paper
discusses non-statin therapies, such as ezetimibe and the newer Proprotein
convertase subtilisin/kexin type 9 Inhibitors (PCSK9-i).
PMID- 29962500
TI - Physician-patient interaction satisfaction and its influence on medication
adherence and type-2 diabetic control in a primary care setting.
AB - INTRODUCTION: Medication adherence has been found to be an important determinant
in achieving glycaemic control in Type 2 Diabetes (T2DM) patients. In other
patient populations, physician-patient interaction satisfaction was found to
influence medication adherence. It is then important to identify if this is also
a factor amongst T2DM patients on insulin as poor adherence was associated with
increased all-cause mortality. METHODS: This was a cross sectional study
involving 197 T2DM patients on insulin from two government primary health clinics
in Gombak. Physician-patient interaction satisfaction was assessed using Skala
Kepuasan Interaksi Perubatan (SKIP-11) consisting of 3 subdomains (Distress
Relief, Rapport and Interaction Outcome). Medication adherence level was measured
using a single item selfreport question. Data analysis for descriptive,
inferential and multivariate analysis statistics were performed. RESULTS: The
mean age of the study participants was 57.12 (SD: 9.27). Majority were Malay,
female, unemployed with mean BMI of 27.5. Majority reported full adherence
(62.9%). High scores in the Interaction Outcome subdomain was associated with
better adherence. Factors associated with high scores in this subdomain included
patient education level, number of oral hypoglycaemic agent and type of insulin
regime taken. This study also found that high scores in the Interaction Outcome
domain is associated with lower HbA1c (p<0.05). CONCLUSION: Physician-patient
interaction satisfaction is an important factor in achieving better medication
adherence which also leads to better glycaemic control in this group of patients.
There is a need to identify strategies to improve satisfaction in this domain to
improve patient adherence.
PMID- 29962501
TI - Ryzophagia secondary to PCOS -related menorrhagia.
AB - We report the peculiar case of a patient who consumed raw rice daily and had iron
deficiency anaemia secondary to menorrhagia with underlying polycystic ovarian
syndrome. A 32-year-old lady of Asian descent presented with symptoms of fatigue,
lethargy and prolonged, irregular periods for the last two months. There was
noticeable increase in body weight, male pattern alopecia and facial acne. In
addition, she experienced sudden, unexplained predilection towards consumption of
raw rice (up to 300- 400g/day). The patient was treated with oral iron and
cyclical progestin. After three weeks, her haemoglobin improved and her
ryzophagia subsided. Gynaecologists should be vigilant of pica, which can occur
outside of the context of pregnancy and also poses potential health risks
including tooth attrition, electrolyte imbalance, intestinal obstruction and
poisoning.
PMID- 29962502
TI - Alopecia secondary to repaired occipital encephalocele - role of tissue expander
in hair restoration.
AB - Partial scalp alopecia is a common problem that can lead to severe social and
psychological problems. Tissue expansion, although an old concept, provides a
surgical alternative to manage areas of alopecia. We describe a case of alopecia
secondary to repaired occipital encephalocele that was successfully treated using
tissue expansion technique.
PMID- 29962503
TI - Protein loosing enteropathy after Fontan procedure.
AB - Fontan and Baudet described the procedure in 1971 and was very useful to improve
the quality of life in many complex cyanotic heart diseases. It has gone through
various modifications since then to improve the outcome. The mortality was
reported as 2.1% and survival rate of at 5 years, 10 years, 15 years and 20 years
were 91%, 80%, 73%and 69% respectively. Though it was a useful palliative
procedure to improve the quality of life, it has complications which may affect
the morbidity and mortality like Protein loosing enteropathy ,reduced exercise
capacity thromboembolism. The patients with protein losing enteropathy present
with Pleural effusion, ascites, and edema and they need periodic replacement of
Albumin and frequent reviews and close follow up in the management to reduce the
mortality and to improve the quality of life .These complications we come across
and they need our support in the management at district level hospitals.
PMID- 29962504
TI - Major tracheobronchial injuries: Management of two rare cases.
AB - Tracheobronchial injuries are uncommon and a high level of suspicion is needed
for immediate diagnosis and prompt treatment. In this case series, two rare cases
of tracheobronchial injuries is described showing variable clinical presentations
with different levels of injury. Our first case was seen in a 20 years old male
whom had a direct impact on the neck and presented with upper tracheal injury. On
arrival, this patient was in respiratory distress and had bilateral pneumothorax.
Bilateral chest tube was inserted with subsequent neck exploration. During the
neck exploration, anastomosis of the injured trachea was performed. The second
case was represented by a 35 years old man with right main bronchial injury. Upon
initial presentation, this patient appeared well and was comfortable under room
air. However he gradually deteriorated one week after the trauma requiring
surgical intervention. Eventually a thoracotomy with primary anastomosis of the
bronchial tear was performed. Details of both cases including clinical
presentation, imaging and procedures done will be discussed in this article.
PMID- 29962505
TI - Is the incidence of cancer in Malaysia falling?
AB - No abstract provided.
PMID- 29962506
TI - Features of post-radioiodine whole body scan in non-invasive Follicular Thyroid
Neoplasm with papillary-like nuclear features (NIFTP).
AB - Recently, encapsulated follicular variant of papillary thyroid carcinoma has been
reclassified as non-invasive follicular thyroid neoplasm with papillary-like
nuclear features (NIFTP) to emphasize the benign nature of this entity. In our
institution, we have assessed 455 patients treated with radioiodine ablation for
differentiated thyroid carcinoma and 20 of them were retrospectively found to
fulfill the new NIFTP criteria. There was no evidence of metastasis on post
radioiodine whole body scans for NIFTP cases and these patients were in remission
subsequently. The benign features of these patients' whole body scans and good
clinical outcome following treatment further support NIFTP as a low risk thyroid
neoplasm.
PMID- 29962507
TI - Expression of the Long Intergenic Non-Coding RNA (lincRNA) of the NED25 Gene
Modulates the microRNA-125b, STAT3, Nitric Oxide, and Procalcitonin Signaling
Pathways in Patients with Sepsis.
AB - BACKGROUND The aim of this study was to investigate the long intergenic non
coding RNA (lincRNA) of the NED25 gene, and the microRNA (miR)-125b, STAT3,
nitric oxide (NO), and procalcitonin (PCT) pathway in sepsis. MATERIAL AND
METHODS Seventy-five age-matched and sex-matched patients were divided into three
groups: 25 patients with sepsis only; 25 patients with septic shock; and 25
healthy control subjects. Computational analysis and a luciferase assay confirmed
that the STAT3 and PCT genes were target genes of miR-125b, whereas the lincRNA
of the NED25 gene was validated as an endogenous lincRNA competing with miR-125b
for binding to STAT3 and PCT. Real-time polymerase chain reaction (PCR) and
Western blot measured the expression of miR-125b, STAT3, and PCT in peripheral
blood monocytes (PBM) transfected with miR-125b mimics, miR-125b inhibitors, or
small interfering (siRNA). RESULTS The expression of miR-125b, the PCT position
ratio, the expression of PCT mRNA and protein were increased when compared with
healthy individuals. When compared with the siRNA negative control, miR-125b and
the lincRNA of the NED25 gene mimics, as well as STAT3 siRNA significantly
downregulated the mRNA and protein expression of STAT3 and PCT; mRNA and protein
expression of STAT3 and PCT in cells transfected with miR-125b inhibitors were
significantly increased. Intracellular nitric oxide (NO) production was
upregulated by miR-125b inhibitors and downregulated by miR-125b mimics or siRNA.
CONCLUSIONS Downregulation of the lincRNA of the NED25 gene was associated with
sepsis in patients by modulating the signaling pathways downstream of miR
125b/STAT3/PCT/NO signaling pathway.
PMID- 29962508
TI - The Use of Cardiac Resynchronization Therapy in Cancer Patients with Heart
Failure.
AB - Objectives: Investigate the use of cardiac resynchronization therapy (CRT) in
cancer patients with heart failure (HF); assess factors associated with ischemic
and non-ischemic HF. Background: Many newer cancer therapies are cardiotoxic;
thus, the incidence of HF has been increasing in this high-risk patient
population. CRT has beneficial effects on morbidity, mortality, and left
ventricular function in patients with non-ischemic cardiomyopathy, yet cancer
patients and survivors who develop severe HF and are eligible for CRT often do
not receive it. Methods: Review of 2 years of echocardiography and
electrocardiography data from cancer patients. Results: Of 272 patients meeting
inclusion criteria for CRT placement (LVEF <=35%, QRS duration >=120 ms), 131
(48.2%) had HF with ischemic etiology and 141 (51.8%) had HF with non-ischemic
etiology. Most patients had solid tumors, including breast, lung, sarcoma, and
lymphoma (73.2%, n=199). Only 21.3% (58/272; 27 ischemic; 31 non-ischemic)
underwent CRT placement, who were mostly women and those with solid tumors. Non
ischemic HF was significantly associated with younger age (<65 years) (OR=0.91;
95% CI=0.87-0.95) and female sex (OR=2.5; 95% CI=1.1-6.0). As expected, ischemic
HF was significantly associated with history of myocardial infarction, diabetes,
and cardiovascular disease. Conclusions: CRT is underutilized in cancer patients
with HF. Most of the cancer patients who did not receive CRT had non-ischemic HF
secondary to chemotherapy. CRT may be less utilized in those patients due to
shortened life expectancy, yet evidence suggests that CRT has beneficial effects
on morbidity, mortality, and left ventricular function. Its use may improve
patient quality of life and allow oncologists to continue cancer treatments that
could prolong survival.
PMID- 29962509
TI - Brain Differences Visualized in the Blind using Tensor Manifold Statistics and
Diffusion Tensor Imaging.
AB - Diffusion tensor magnetic resonance imaging (DTI) reveals the local orientation
and integrity of white matter fiber structure based on imaging multidirectional
water diffusion. Group differences in DTI images are often computed from single
scalar measures, e.g., the Fractional Anisotropy (FA), discarding much of the
information in the 6-parameter symmetric diffusion tensor. Here, we compute
multivariate 6D tensor statistics to detect brain morphological changes in 12
blind subjects versus 14 sighted controls. After Log-Euclidean tensor denoising,
images were fluidly registered to a common template. Fluidly-convected tensor
signals were re-oriented by applying the local rotational and translational
component of the deformation. Since symmetric, positive-definite matrices form a
non-Euclidean manifold, we applied a Riemannian manifold version of the
Hotelling's T2 test to the logarithms of the tensors, using a log-Euclidean
metric. Statistics on the full 6D tensor-valued images outperformed univariate
analysis of scalar images, such as the FA and the geodesic anisotropy (GA).
PMID- 29962510
TI - Unique Raman Spectroscopic Fingerprints of B-Cell Non-Hodgkin Lymphoma:
Implications for Diagnosis, Prognosis and New Therapies.
AB - Objective: Raman spectroscopy is a non-invasive laser-based technique that
identifies molecular chemical composition of tissues and cells. The objective of
the work was to demonstrate that unique Raman spectroscopic fingerprints of B
cell non-Hodgkin lymphoma cells could be distinguished from normal B-cells.
Methods: Normal B-cells and B-cell non-Hodgkin lymphoma cells were mounted on
aluminum slides and analyzed by Raman spectroscopy using Asymmetric Least Squares
and Principal Component Analysis. Results: Clustering by Principal Component
Analysis differentiated normal B-cells from B-cell non-Hodgkin lymphoma cells as
well as between the different B-cell non-Hodgkin lymphoma cell types.
Conclusions: Raman spectroscopy technology provided a different paradigm in
analyzing tumor cells which could be used for diagnosis as well as contribute new
information on unique characteristics of cancer cells to understand pathogenesis
and potential novel treatments.
PMID- 29962511
TI - Knowledge will Propel Machine Understanding of Content: Extrapolating from
Current Examples.
AB - Machine Learning has been a big success story during the AI resurgence. One
particular stand out success relates to learning from a massive amount of data.
In spite of early assertions of the unreasonable effectiveness of data, there is
increasing recognition for utilizing knowledge whenever it is available or can be
created purposefully. In this paper, we discuss the indispensable role of
knowledge for deeper understanding of content where (i) large amounts of training
data are unavailable, (ii) the objects to be recognized are complex, (e.g.,
implicit entities and highly subjective content), and (iii) applications need to
use complementary or related data in multiple modalities/media. What brings us to
the cusp of rapid progress is our ability to (a) create relevant and reliable
knowledge and (b) carefully exploit knowledge to enhance ML/NLP techniques. Using
diverse examples, we seek to foretell unprecedented progress in our ability for
deeper understanding and exploitation of multimodal data and continued
incorporation of knowledge in learning techniques.
PMID- 29962512
TI - Ethical Considerations and Dilemmas Before, during and after Fieldwork in Less
Democratic Contexts: some Reflections from Post-Uprising Egypt.
AB - How do we conduct ethically sound social research in less- or non-democratic
settings? Here, the 'ethical guidelines,' or 'codes of conduct' outlined by our
professional organizations provide some, albeit only insufficient guidance. In
such contexts, issues like informed consent or the avoidance of harm to research
participants have to be - based on a careful analysis of the situation on the
ground - operationalized. What are, considering the particular social and
political context in the field, the potential risks for interviewees and the
researcher, and what can be done to eliminate or at least mitigate these risks?
Reflecting on extensive fieldwork on the role of the prodemocracy movement during
the Egyptian Uprising of 2011 in the wake of the so-called 'Arab Spring,' this
study illustrates how rather abstract ethical considerations can be handled
practically in an environment that is characterized by increasing levels of
political repression and decreasing civil liberties. It is in such contexts that
a failure to carefully consider such ethical questions entails a very real risk
of endangering the livelihoods and even lives of research participants.
Furthermore, it is shown that these and similar issues are not only of critical
importance when designing a research project, but that they might have to be
revisited and renegotiated at later stages of the research process - even after
the conclusion of the data collection phase. Here, questions of data protection,
anonymity of informants, and the associated 'do no harm' principle are
particularly pertinent.
PMID- 29962513
TI - Larregue's Critique of Cofnas et al. (2017): A Rejoinder.
AB - Data from the General Social Survey indicate that conservatives' self-reported
trust in scientists has steadily decreased since 1974. In Cofnas et al. (The
American Sociologist, 2017), we suggested that this trend may have been partly
driven by the increasing tendency of scientific institutions, and the
representatives of such institutions, to distort social science for the sake of
liberal activism. Larregue (The American Sociologist, 2017) makes three opposing
arguments: (1) It is "very hard" to establish the charge of bias, especially
since we did "not state what [we] mean by 'bias.'" (2) We did not establish a
causal relationship between scientists' (alleged) liberal activism and
conservatives' distrust of science, and we ignored activism by conservative
scientists. (3) We were wrong to advocate "affirmative action" for conservatives
in academia. We address these arguments in turn: (1) Larregue does not engage
with our main arguments that liberal bias exists in social science. (2) In recent
years, prominent scientific organizations have, with great publicity, intervened
in policy debates, always supporting the liberal side without exception. It is
not unreasonable to assume that this would diminish conservatives' trust in these
organizations. Contra Larregue, in Cofnas et al. (The American Sociologist, 2017)
we explicitly acknowledged that conservative scientists can also be biased. (3)
We never advocated "affirmative action" for conservatives, and in fact we object
to such a proposal.
PMID- 29962514
TI - Phytochemical and Biological Studies on Ziziphora bungeana.
PMID- 29962515
TI - Asthma Control During Pregnancy: Avoiding Frequent Pitfalls.
PMID- 29962516
TI - Fertility Preservation for Patients with Malignant Disease. Guideline of the
DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017) -
Recommendations and Statements for Girls and Women.
AB - Aim: The aim of this official guideline published by the German Society of
Gynecology and Obstetrics (DGGG) and coordinated with the German Society of
Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to
provide consensus-based recommendations, obtained by evaluating the relevant
literature, on counseling and fertility preservation for prepubertal girls and
boys as well as patients of reproductive age. Statements and recommendations for
girls and women are presented below. Statements or recommendations for boys and
men are not the focus of this guideline. Methods: This S2k guideline was
developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM
and represents the structured consensus of representative members from various
professional associations (n = 40). Recommendations: The guideline provides
recommendations on counseling and fertility preservation for women and girls
which take account of the patient's personal circumstances, the planned oncologic
therapy and the individual risk profile as well as the preferred approach for
selected tumor entities.
PMID- 29962518
TI - Does the Degree of Acculturation Influence Breastfeeding Intention and Start or
the Frequency of Early Weaning? Results of a Prospective Observational Study.
AB - Objectives: Recent breastfeeding studies from immigration countries have found
that acculturation factors influence breastfeeding behaviour in women with a
migration background. To date, there has been no systematic investigation for
Germany. Therefore, we study whether and how the degree of acculturation within a
population of migrant women influences the start, time and duration of
breastfeeding. Patient Population and Methodology: Pregnant women who were
admitted to one of the three participating maternity clinics in Berlin for the
birth of their child in the one-year study period were surveyed (including
sociodemographic details, data on migration/acculturation). These women were
interviewed again two or three days post partum (including start of
breastfeeding, planned breastfeeding duration, reasons for not breastfeeding). In
a subgroup, a telephone interview took place 6 months post partum about the
actual breastfeeding duration, contraceptive behaviour post partum and availing
of midwife services following delivery. Breastfeeding behaviour was analysed
using multivariate regression models, among other things. Results: The prepartum
survey included 7100 women, 6884 women were contacted in the postnatal wards, and
the subgroup six months after delivery comprised 605 women. No acculturation
related differences were found in the start of breastfeeding. In the adjusted
model, a medium and higher degree of acculturation diminished the chance of
planning a long breastfeeding period. More acculturated women show a greater risk
of weaning within the first six months than less acculturated women. Conclusion:
The degree of acculturation has relevant significance for some aspects of
breastfeeding behaviour in women with a migration background. This should be
considered both in breastfeeding promotion programmes and in further national
breastfeeding studies.
PMID- 29962517
TI - Controversies about the Secondary Prevention of Spontaneous Preterm Birth.
AB - Preterm birth is one of the major global health problems and part of the
Millennium Development goals because of the associated high number of perinatal
or neonatal mortality and long-term risks of neurodevelopmental and metabolic
diseases. Transvaginal sonography has meanwhile been established as a screening
tool for spontaneous preterm birth despite its relatively low sensitivity when
considering only the cervical length. Vaginal progesterone has been shown to
reduce prematurity rates below 34 weeks in a screening population of singleton
pregnancies. Up to now, no positive long-term effect could be demonstrated after
2 years. It seems to have no benefit to prolong pregnancies after a period of
preterm contractions and in risk patients without cervical shortening. Meta
analyses still demonstrate conflicting results dependent on quality criteria used
for selection. A cerclage is only indicated in singleton pregnancies with
previous spontaneous preterm birth and a combined cervical shortening in the
current pregnancy. Nevertheless, the short- and long-term outcome has never been
evaluated, whereas maternal complications may be increased. There is no evidence
for a prophylactic cervical cerclage in twin pregnancies even in cases with
cervical shortening. Emergency cerclage remains an indication after individual
counseling. The effect of a cervical pessary in singleton pregnancy seems to be
more pronounced in studies where a few investigators with increasing experience
have treated and followed the patients at risk for preterm birth. Mainly in twin
pregnancies, pessary treatment seems to be promising compared to other treatment
options of secondary prevention when the therapy is started at early stages of
precocious cervical ripening. At present, several international trials with the
goal to reduce global rates of prematurity are in progress which will hopefully
allow to specify the indications and methods of intervention for certain
subgroups. When trials are summarized, prospective meta-analyses carry a lower
risk of bias than the meanwhile uncontrolled magnitude of retrospective meta
analyses with conflicting results.
PMID- 29962520
TI - Comments on Published Article: A valuable resource.
PMID- 29962519
TI - Opportunistic Salpingectomy at the Time of Benign Laparoscopic Hysterectomy:
Assessment of Possible Complications and Histopathological p53-Signatures.
AB - Introduction: The aim of this study is to assess the prevalence of tubal
histopathological abnormalities (serous tubal intraepithelial carcinoma STIC and
p53 signatures) and the prevalence of perioperative and postoperative
complications related to opportunistic laparoscopic salpingectomy in a low risk
population. Materials and Methods: In this observational prospective cohort,
prophylactic bilateral salpingectomy during benign laparoscopic hysterectomy was
systematically performed in 100 consecutive women. Peri- and postoperative
complications were registered. Duration of salpingectomy and post-salpingectomy
blood loss were also measured. Histopathological and immunohistochemical analysis
with anti-p53 antibody were performed on the whole fallopian tubes according to a
specific and validated protocol. Results: Laparoscopic salpingectomy was always
possible without any peri- or postoperative complication attributable to the
salpingectomy itself. The mean duration was 428 seconds (354 - 596) and the blood
loss was 9 cm 3 (2 - 15). Using histopathological and immunohistochemical
assessment with anti-p53 antibody on 199 fallopian tubes (99 bilateral
salpingectomies and one unilateral salpingectomy because of previous
salpingectomy for ectopic pregnancy), there was a prevalence of 5.52% (11/199) of
p53 signatures. No STIC were observed and no associated cancer. Conclusions:
Laparoscopic salpingectomy is both feasible and innocuous during benign
hysterectomy. Meticulous histopathologic examination of the tubes may reveal
specific abnormalities.
PMID- 29962522
TI - Accuracy of skin temperature over carotid artery in estimation of core
temperature in infants and young children during general anaesthesia.
AB - Background and Aims: Core temperature monitoring is essential in children under
general anaesthesia as they are more susceptible to hypothermia. We aimed to use
skin temperature over the carotid artery (Tsk-carotid) with correction factors
(Cf) to estimate core temperature. Primary outcome measure was to assess the
sensitivity of Tsk-carotid with Cf for detecting hypothermia. Secondary outcome
measure was to assess the specificity of Tsk-carotid with Cf for detecting
hypothermia. Methods: First consecutive 50 patients fulfilling the inclusion
criteria were included in modelling group and next 60 in the validation group. In
the modelling group, average estimation error between Tsk-carotid and Tnaso was
calculated and Cf was derived by multiple regression analysis (body surface area
to mass ratio, body fat %, room temperature, relative humidity and warm Gamgee).
In the validation group, Cf derived was used to predict Tnaso using Tsk-carotid
by the formula: Tnaso-predicted = Tsk-carotid + Cf. Bland-Altman plots were used
to assess the agreement between Tsk-carotid with Cf and Tnaso in the validation
group. Results: The sensitivity for detecting hypothermia with the use of Tsk
carotid and Cf was 100%. The final Cf derived was 0.064 * (room temperature)
2.65. Most of the measurements fell within 95% confidence limit of Bland-Altman
plot; 95% confidence interval (0.504-[-0.451]). The specificity of this method
was 11%. Conclusion: This method overestimated hypothermia in most cases and
cannot be accurately used as a measure of core temperature monitoring
perioperatively.
PMID- 29962521
TI - Intraoperative magnetic resonance imaging for neurosurgery - An
anaesthesiologist's challenge.
AB - Intraoperative magnetic resonance imaging (MRI)-guided neurosurgery has gained
popularity over the years globally. These surgeries require a dedicated operating
room and MRI-compatible anaesthesia equipment. The anaesthesiologist providing
care in this setup needs to be experienced and vigilant to ensure patient safety.
Strict adherence to MRI safety checklists and regular personnel training would
avoid potential accidents and life-threatening emergencies. Teamwork, good
communication, preprocedure planning, and familiarity with the surroundings are
very important for safe care and good outcomes. We performed a literature search
in Google Scholar, PubMed and Cochrane databases for original and reviewed
articles for the origins, development and applications of intraoperative MRI in
neurosurgical procedures. Much of the research has emphasised on the surgical
indications than the anaesthetic challenges faced during intraoperative MRI
guided surgery. The purpose of this review is to discuss the anaesthetic concerns
specific to this unique environment.
PMID- 29962523
TI - Paravertebral block with morphine or dexmedetomidine as adjuvant to bupivacaine
for post-operative analgesia in modified radical mastectomy: A prospective,
randomised, double-blind study.
AB - Background and Aims: General anaesthesia (GA) is the standard technique and
paravertebral block (PVB) is suggested as an ideal analgesic in patients
undergoing modified radical mastectomy (MRM). This study assessed post-operative
analgesic efficacy of morphine or dexmedetomidine as adjuvant to bupivacaine in
PVB. Methods: Forty-five women (18-60 years) undergoing MRM +/- axillary
clearance received PVB with 20 ml bupivacaine 0.25% with morphine 3 mg (Group BM)
or dexmedetomidine 1 MUg/kg (Group BD) in this prospective, randomised, double
blind study. After confirming the onset of PVB, standardised GA induction
sequence was used. Intra-operative consumption of fentanyl and propofol along
with postoperative morphine and diclofenac consumption, numerical rating scores
(NRS) for pain at rest and on movement, nausea and vomiting scores, sedation
scores and time to rescue analgesic were recorded. Chi-square or Fisher's exact
test and Kruskal-Wallis followed by Mann-Whitney U-test were applied as
applicable. Results: The number of patients requiring morphine during first 2-h
post-operatively was significantly lower (P = 0.006) in Group BM. The mean dose
of morphine in Group BM (0.84 [2.41] mg) and Group BD (1.70 [1.84] mg) was
comparable (P = 0.187). NRS for pain at rest and on movement was significantly
lower in Group BM at 2, 6, 12 and 18 h. The duration of analgesia was
significantly prolonged in Group BM (1019.8 [422.9] min) than in Group BD (263.7
[194.9] min) (P < 0.001). Conclusion: Morphine is superior adjuvant to
bupivacaine in PVB for modified radical mastectomy than dexmedetomidine.
PMID- 29962524
TI - Multimodal temperature management during donor hepatectomy under combined general
anaesthesia and neuraxial analgesia: Retrospective analysis.
AB - Background and Aims: Unintended hypothermia (UIH) during surgery under general
anaesthesia has adverse implications. A retrospective analysis of the
perioperative temperature records of healthy voluntary liver donors was done to
evaluate the efficacy of a multimodal protocol for temperature management.
Methods: Records of 50 American Society of Anesthesiologists physical status
Class 1 patients operated for Donor Hepatectomy lasting >2 h under combined
general and epidural anaesthesia were analysed. Ambient temperature was
maintained 24 degrees C-27 degrees C before induction of GA and during insertion
of epidural catheter. Active warming was done using warming mattress set to
temperature 38 degrees C, hot air blanket with temperature set to 38 degrees C
and fluid warming device (HotlineTM) with preset temperature of 41 degrees C.
Nasopharyngeal temperature was continuously monitored. After induction of GA and
draping of the patient, ambient temperature was decreased and maintained at 21
degrees C-24 degrees C and was again increased to 24 degrees C-27 degrees C at
the conclusion of surgery. During surgery, for every 0.1 degrees C above 37
degrees C, one heating device was switched off such that at 37.3 degrees C all
the 3 devices were switched off. Irrigation fluid was pre-warmed to 39 degrees C.
Results: Baseline temperature was 35.9 degrees C +/- 0.4 degrees C. Minimum
temperature recorded was 35.7 degrees C +/- 0.4 degrees C. Mean decrease in
temperature below the baseline temperature was 0.2 degrees C +/- 0.2 degrees C.
Temperature at the end of surgery was 37.4 degrees C +/- 0.5 degrees C.
Conclusion: Protocol-based temperature management with simultaneous use of
resistive heating mattress, forced-air warming blanket, and fluid warmer along
with ambient temperature management is an effective method to prevent unintended
perioperative variation in body temperature.
PMID- 29962525
TI - A randomised controlled study of the post-operative analgesic efficacy of
ultrasound-guided pectoral nerve block in the first 24 h after modified radical
mastectomy.
AB - Background and Aims: Breast cancer has become the most common cancer in women
worldwide. Acute post-operative pain following mastectomy remains a challenge for
the anaesthesiologist despite a range of treatment options available. The present
study aimed to compare the post-operative analgesic efficacy of pectoral nerve
(Pecs) block performed under ultrasound with our standard practice of opioids and
non-steroidal anti-inflammatory drugs for mastectomy. Methods: This randomised
controlled study was conducted at a tertiary care teaching hospital in India,
after obtaining ethical clearance. Fifty adult female patients posted for
elective unilateral modified radical mastectomy were divided into two groups as
follows: Group I (general anaesthesia only) and Group II (general anaesthesia
plus ultrasound-guided Pecs block), each comprising 25 patients. Post
randomisation, patients in Group I received general anaesthesia, while Group II
patients received ultrasound-guided Pecs block followed by general anaesthesia
after 20 min. The primary outcome was measured as patient-reported pain intensity
using Visual Analogue Scale (VAS) at rest. Statistical analysis was performed
using Student's t-test and Mann-Whitney U-test. Data were entered into MS Excel
spreadsheet and analysis was performed using the Statistical Package for the
Social Sciences version 23.0. Results: VAS score was significantly lower in Group
II at rest and on abduction post-operatively at all time intervals (P < 0.001).
The 24-h tramadol consumption was significantly less in Group II compared to
Group I (114.4 +/- 4.63 mg vs. 402.88 +/- 74.22, P < 0.0001). Conclusion: Pecs
block provided excellent post-operative analgesia in the first 24 h.
PMID- 29962526
TI - Anaesthetic management of robotic-assisted gynaecology surgery in the morbidly
obese - A case series of 46 patients in a UK university teaching hospital.
AB - Background and Aims: The evolution of robotic technology has enhanced the scope
of laparoscopic surgery. Morbid obesity [body mass index (BMI) >40 kg/m2] due to
significant physiological attributes presents a significant surgical and
anaesthetic challenge. Robotic surgery in this subset of patients can present
with its own problems due to surgical requirements of prolonged pneumoperitoneum
and steep Trendelenburg position. Methods: We reviewed the anaesthetic management
of 46 morbidly obese patients undergoing robotic-assisted laparoscopic
gynaecology surgery. Patient characteristics, anaesthetic management, length of
hospital stay (LOS), complications, and readmissions within 30 days were noted.
Mean with standard deviation was used for statistical analysis. Results: The mean
[standard deviation (SD)] weight and BMI were 121.2 (18.49) kg and 47.83 (7.89)
kg/m2, respectively. The mean (SD) anaesthetic and surgical times were 229 (75.9)
and 167.7 (62.7) min, respectively. The mean (SD) LOS was 1.57 (1.03) days. About
70% of patients were discharged on the first day after surgery. Six patients
needed critical care support. There were two readmissions within 30 days.
Conclusion: Good preparation, teamwork, and multidisciplinary input helped us to
conduct complex robotic-assisted and long-duration surgery in morbidly obese
patients with minimal complications.
PMID- 29962527
TI - Post-operative bilateral continuous ultrasound-guided transversus abdominis plane
block versus continuous local anaesthetic wound infusion in patients undergoing
abdominoplasty.
AB - Background and Aims: Transversus abdominis plane (TAP) block and continuous local
anaesthetic wound infusion are used as part of multimodal analgesia to treat
postoperative pain after lower abdominal surgeries. The aim of this randomised
controlled study was to assess the efficacy of the two techniques and compare the
two in patients undergoing abdominoplasty. Methods: Ninety female patients
undergoing abdominoplasty were allocated to receive continuous wound infusion
with saline (control group, GC, n = 30), continuous bilateral TAP block with
0.25% levobupivacaine (group GT, n = 30), or continuous wound infusion with 0.25%
levobupivacaine (group GW, n = 30). The primary end-point was morphine
requirement in the first 48 h. Numerical rating scale (NRS) at rest and during
movement, time to first morphine dose and time to first ambulation were recorded.
Results: Morphine requirement in the first 48 h was significantly higher in GC
than GW and GT (61.9 +/- 12.8, 21.5 +/- 9.5, and 18.9 +/- 8.1 mg, respectively; P
= 0.001), but GW and GT were comparable (P = 0.259). NRS was significantly higher
in GC during movement in the first 24 h. GW and GT showed significantly longer
time to first morphine dose (6.5 +/- 1.7 and 8.9 +/- 1.4 h, respectively, vs. 1.2
+/- 0.3 h in GC) and significantly shorter time to first ambulation (7.8 +/- 3.1
and 6.9 +/- 3.4 h, respectively, vs. 13.2 +/- 4.9 h in GC) (P = 0.001).
Conclusion: Continuous bilateral ultrasound-guided TAP block and continuous local
anaesthetic wound infusion significantly decreased total morphine consumption in
the first 48 h compared to placebo; however, both treatment techniques were
comparable.
PMID- 29962528
TI - Comparision of Ambu AuraGainTM and LMA(r) ProSeal in children under controlled
ventilation.
AB - Background and Aims: The LMA ProSeal(r) is considered a prototype among the
second-generation supraglottic airway devices (SAD). The Ambu AuraGainTM is a
relatively new, single use, second-generation SAD with a preformed shape. We
conducted this study with the aim of comparing the difference in clinical
performance between Ambu AuraGainTM and LMA ProSeal(r) in children receiving
controlled ventilation. Methods: Ninety-four children, aged between 6 months to
12 years, weighing 5 to 30 kg, belonging to American Society of Anesthesiologists
Physical Status I and II, undergoing elective surgical procedures, were
randomized into two groups. The primary end-point was oropharyngeal seal
pressure, and the secondary parameters were the number of attempts, time of
insertion, ease of placement of the device and gastric tube, and fiberoptic
visualization of the laryngeal aperture. Results: The mean oropharyngeal seal
pressure with Ambu AuraGainTM was significantly higher than LMA ProSeal(r) (23.3
+/- 4.6 cmH2O vs 20.6 +/- 4.8 cmH2O, P = 0.007, respectively). The ease and
success rate for device placement, fiberoptic visualization of the larynx, and
complications were comparable. However, the time for insertion in Ambu AuraGainTM
group was shorter when compared to LMA ProSeal(r) group, median (IQR [range]); 12
(10-15) s vs 20 (18-23) s (P < 0.001), respectively. The gastric drain was
significantly easier to insert in Ambu AuraGainTM compared to LMA(r) ProSeal (P =
0.01). Conclusion: Our study suggests that Ambu AuraGainTM could be a useful
disposable alternative to LMA ProSeal(r) for securing airway in children.
PMID- 29962530
TI - Delayed emergence from anaesthesia and bilateral mydriasis following bilateral
pallidotomy.
AB - Pallidotomy is a surgical procedure done widely for Parkinson's disease and
various dystonias refractory to medical treatment. The technique involves
radiofrequency (RF) thermal coagulation of globus pallidus internus, either
unilaterally or bilaterally. The technique has been shown to produce good
success. However, the involvement of nearby vital structures can result in new
post-operative complications. We encountered a case of delayed emergence from
anaesthesia associated with bilateral mydriasis and visual field defects in a
patient after bilateral RF thermal lesioning.
PMID- 29962529
TI - Efficacy and safety of Parecoxib for prevention of catheter-related bladder
discomfort in patients undergoing transurethral resection of bladder tumor:
Prospective randomised trial.
AB - Background and Aims: Catheter-related bladder discomfort (CRBD) is the urge to
void or discomfort in the suprapubic region secondary to an indwelling urinary
catheter. We aimed to evaluate the safety and efficacy of single-dose of
intravenous parecoxib in reducing the incidence and severity of CRBD in patients
undergoing transurethral resection of bladder tumor (TURBT). Methods: Sixty-one
adult patients, American Society of Anesthesiologists physical status I or II,
undergoing elective TURBT under spinal anaesthesia, were randomly allocated to
receive 40 mg of IV parecoxib (group P; n = 29) or an equal volume of normal
saline (control group C; n = 32). CRBD was graded as none, mild, moderate, and
severe. Between-group comparisons were made for the incidence and severity of
CRBD, postoperative Visual analog scales (VAS), rescue analgesia equirements, and
occurrence of adverse events. Statistical analysis done with the Mann-Whitney U
test and Fisher's Exact Test. A P value of <= 0.05 was considered statistically
significant. Results: Parecoxib significantly reduced the incidence and severity
of CRBD at 2, 4, 6, and 12 hours postoperatively compared to placebo (P < 0.05).
Median pain VAS scores were lower in the P group at all times except the first
hour. Rescue analgesia was given to more patients in group C (16/32, 50%) than in
group P (1/29) (P < 0.001). None of the patients who received parecoxib
experienced an adverse event. Conclusion: A single intravenous injection of
parecoxib is safe and effective in decreasing the incidence and severity of CRBD
in patients undergoing TURBT. Trial Registration Identifier:
NCT02729935(www.clinicaltrials.gov).
PMID- 29962531
TI - Brachytherapy implant insertion in head-and-neck cancer: Results of anaesthetic
technique at a tertiary care hospital.
PMID- 29962532
TI - Air- Q intubating laryngeal airway guided intubation in Morquio syndrome.
PMID- 29962533
TI - Methaemoglobinaemia: Recognition and realisation at bedside.
PMID- 29962534
TI - Difficult intubation: 'Beyond the vocal cords'.
PMID- 29962535
TI - Oral gastroscope-guided bougie insertion and endotracheal intubation.
PMID- 29962536
TI - Neuromuscular monitoring: An assistant not an alternative.
PMID- 29962537
TI - Reversal agent is mandatory even with neuromuscular monitoring!
PMID- 29962538
TI - Reversal of neuromuscular block.
PMID- 29962539
TI - Response to comments on "Reversal agents: Do we need to administer with
neuromuscular monitoring".
PMID- 29962540
TI - Enantiomerically Enriched alpha-Methyl Amino Acids. Use of an Acyclic, Chiral
Alanine-Derived Dianion with a High Diastereofacial Bias.
AB - Hindered esters derived from N-benzoylalanine and the following chiral alcohols
have been synthesized: (1) (-)-isopinocampheol; (2) (-)-trans-2
phenylcyclohexanol and (3) (-)-8-phenylmenthol. Sequential treatment of these
esters with LDA (1.2 equiv.) and n-butyllithium (2.4 equiv.) at -78 degrees C in
THF generates the corresponding chiral dianions. Alkylation of each of these with
benzyl bromide reveals that only the (-)-8-phenylmenthyl auxiliary confers a high
diastereofacial bias upon its derivative dianion. In fact, that dianion (6)
consistently displays diastereomeric ratios in the range of 89:11 to 94:6 for
alkylations with a spectrum of nine alkyl halides. If one recrystallization step
is included, a single diastereomeric product may be obtained, as is demonstrated
for the benzylation of 6. Of particular note, the alkylation with 3,4-bis(tert
butyldimethylsilyloxy)benzyl bromide (18) (94:6 diast. ratio, 72% yield)
constitutes a formal synthesis of the clinically important antihypertensive (S)
alpha-methyl-DOPA (Aldomet), in enantiomerically enriched from. In all cases
studied, yields are markedly improved, yet diastereoselectivities unchanged, by
the addition of 10% HMPA to the reaction milieu. The (-)-8-phenylmenthol chiral
auxiliary is conveniently recovered via ester cleavage with KO2/18-crown-6,
following alkylation. Complete deprotection affords enantiomerically enriched (S)
alpha-methyl amino acids, in all cases examined, indicating that dianion 6
displays a substantial bias in favor of si face alkylation. This sense of
diastereoselection is consistent with a chain-extended, internal chelate model
for the reactive conformation of the dianion.
PMID- 29962541
TI - A Convenient Synthesis of L-alpha-Vinylglycine from L-Homoserine Lactone.
AB - A procedure for the synthesis of L-alpha-vinylglycine from L-homoserine lactone
is described. The route developed is convenient (only one chromatography step is
required) and efficient (72% yield; >=95% optical yield over 4 steps). Key
features include the use of acid-labile protecting groups for the amino (Boc) and
carboxyl (diphenylmethyl ester) groups, and the use of the phenylselenolate
equivalent derived from sodium borohydride and diphenyl diselenide for L
homoserine lactone cleavage.
PMID- 29962543
TI - Universal health coverage and chronic kidney disease in India.
PMID- 29962544
TI - Preventing hepatitis B virus infection: milestones and targets.
PMID- 29962545
TI - Public health round-up.
PMID- 29962546
TI - Crisis-driven cholera resurgence switches focus to oral vaccine.
AB - Oral rehydration was once the mainstay of treatment for cholera, but today's
cholera outbreaks fuelled by conflict and instability require a new approach.
Sophie Cousins reports.
PMID- 29962547
TI - Japan renews primary health care to promote healthy ageing.
AB - Yoshitake Yokokura has been driving efforts to renew primary health care in Japan
to meet the needs of an ageing population. He talks to Fiona Fleck.
PMID- 29962548
TI - Involving male partners in maternity care in Burkina Faso: a randomized
controlled trial.
AB - Objective: To determine whether an intervention to involve the male partners of
pregnant women in maternity care influenced care-seeking, healthy breastfeeding
and contraceptive practices after childbirth in urban Burkina Faso. Methods: In a
non-blinded, multicentre, parallel-group, superiority trial, 1144 women were
assigned by simple randomization to two study arms: 583 entered the intervention
arm and 561 entered the control arm. All women were cohabiting with a male
partner and had a low-risk pregnancy. Recruitment took place at 20 to 36 weeks'
gestation at five primary health centres in Bobo-Dioulasso. The intervention
comprised three educational sessions: (i) an interactive group session during
pregnancy with male partners only, to discuss their role; (ii) a counselling
session during pregnancy for individual couples; and (iii) a postnatal couple
counselling session. The control group received routine care only. We followed up
participants at 3 and 8 months postpartum. Findings: The follow-up rate was over
96% at both times. In the intervention arm, 74% (432/583) of couples or men
attended at least two study sessions. Attendance at two or more outpatient
postnatal care consultations was more frequent in the intervention than the
control group (risk difference, RD: 11.7%; 95% confidence interval, CI: 6.0 to
17.5), as was exclusive breastfeeding 3 months postpartum (RD: 11.4%; 95% CI: 5.8
to 17.2) and effective modern contraception use 8 months postpartum (RD: 6.4%;
95% CI: 0.5 to 12.3). Conclusion: Involving men as supportive partners in
maternity care was associated with better adherence to recommended healthy
practices after childbirth.
PMID- 29962549
TI - Estimating health plan costs with the OneHealth tool, Cambodia.
AB - Objective: To do resource and cost projections for the entire Cambodian health
sector using the OneHealth tool, during the development of the third national
health strategic plan 2016-2020. Methods: Through a consultative process, the
health ministry estimated the needed and available resources to implement the
strategic plan. The health ministry used the OneHealth Tool to estimate costs of
expanding public sector service provision and compared these to estimates of
projected available financing. Cost estimates covered implementation of health
programmes including commodities and programme management costs, and six cross
cutting health system strengthening components. The tool is populated with local
demographic, epidemiological, programmatic and unit cost data. We present costs
in constant 2015 United States dollars (US$). Findings: We estimated the five
year cost of the strategic plan to be US$ 2973.8 million. Costs are split between
health systems strengthening components (US$ 1516.3 million) and investments in
individual disease or public health programmes (US$ 1457.5 million). Health
programmes for maternal and neonatal health (US$ 367 million), child health and
immunization (US$ 197 million) and noncommunicable disease (US$ 157 million) have
the highest costs. Although projected resource needs increase over time, a
financial space analysis with ambitious projected increases in government funding
indicates that government and donor funding jointly could be sufficient to cover
the cost of the strategic plan from 2018 to 2020. Conclusion: The results both
informed development of the strategic plan, and contributed to the evidence base
for improved budgeting, resource mobilization strategies and stronger overall
public sector financial planning.
PMID- 29962550
TI - Cash interventions to improve clinical outcomes for pulmonary tuberculosis:
systematic review and meta-analysis.
AB - Objective: To assess cash transfer interventions for improving treatment outcomes
of active pulmonary tuberculosis in low- and middle-income countries. Methods: We
searched PubMed(r), Embase(r), Cochrane Library and ClinicalTrials.gov for
studies published until 4 August 2017 that reported on cash transfer
interventions during the treatment of active pulmonary tuberculosis in low- and
middle-income countries. Our primary outcome was a positive clinical outcome,
defined as treatment success, treatment completion or microbiologic cure. Using
the purchasing power parity conversion factor, we converted the amount of cash
received per patient within each study into international dollars (Int$). We
calculated odds ratio (OR) for the primary outcome using a random effects meta
analysis. Findings: Eight studies met eligibility criteria for review inclusion.
Seven studies assessed a tuberculosis-specific intervention, with average amount
of cash ranging from Int$ 193-858. One study assessed a tuberculosis-sensitive
intervention, with average amount of Int$ 101. Four studies included non-cash co
interventions. All studies showed better primary outcome for the intervention
group than the control group. After excluding three studies with high risk of
bias, patients receiving tuberculosis-specific cash transfer were more likely to
have a positive clinical outcome than patients in the control groups (OR: 1.77;
95% confidence interval: 1.57-2.01). Conclusion: The evidence available suggests
that patients in low- and middle-income countries receiving cash during treatment
for active pulmonary tuberculosis are more likely to have a positive clinical
outcome. These findings support the incorporation of cash transfer interventions
into social protection schemes within tuberculosis treatment programmes.
PMID- 29962551
TI - Long-term impact of infant immunization on hepatitis B prevalence: a systematic
review and meta-analysis.
AB - Objective: To conduct a systematic review and meta-analysis of the long-term
impact of infant vaccination on the prevalence of hepatitis B virus (HBV)
infection at the population level. Methods: We searched online databases for
articles reporting comparisons between population cohorts aged >= 15 years who
were exposed or unexposed to infant HBV immunization programmes. We categorized
programmes as universal or targeted to infants whose mothers were positive for
hepatitis B surface antigen (HBsAg). We included studies reporting prevalence of
hepatitis B core antibody (HBcAb), HBsAg, or both. We evaluated the quality of
the study methods and estimated the relative reduction in the prevalence of
infection. Findings: Of 26 studies that met the inclusion criteria, most were
from China (20 studies). The prevalence of HBV infection in unvaccinated and
universally vaccinated cohorts ranged from 0.6% (116 of 20 305 people) to 16.3%
(60/367) and from 0.3% (1/300) to 8.5% (73/857), respectively. Comparing cohorts
with universal vaccination to those without vaccination, relative prevalences
were 0.24 (95% confidence interval, CI: 0.16-0.35) for HBsAg and 0.23 (95% CI:
0.17-0.32) for HBcAb. For populations with targeted vaccination, relative
prevalences were 0.32 (95% CI: 0.24-0.43) and 0.33 (95% CI: 0.23-0.45),
respectively. Conclusion: The residual burden of infection in cohorts offered
vaccination suggests that longer-term evaluations of vaccination coverage,
timeliness and other aspects of programme quality are needed. As HBV-vaccinated
infant cohorts reach adulthood, ongoing analysis of prevalence in adolescents and
young adults will ensure that elimination efforts are on track.
PMID- 29962552
TI - Classification of patient-safety incidents in primary care.
AB - Primary care lags behind secondary care in the reporting of, and learning from,
incidents that put patient safety at risk. In primary care, there is no
universally agreed approach to classifying the severity of harm arising from such
patient-safety incidents. This lack of an agreed approach limits learning that
could lead to the prevention of injury to patients. In a review of research on
patient safety in primary care, we identified 21 existing approaches to the
classification of harm severity. Using the World Health Organization's (WHO's)
International Classification for Patient Safety as a reference, we undertook a
framework analysis of these approaches. We then developed a new system for the
classification of harm severity. To assess and classify harm, most existing
approaches use measures of symptom duration (11/21), symptom severity (11/21)
and/or the level of intervention required to manage the harm (14/21). However,
few of these approaches account for the deleterious effects of hospitalization or
the psychological stress that may be experienced by patients and/or their
relatives. The new classification system we developed builds on WHO's
International Classification for Patient Safety and takes account not only of
hospitalization and psychological stress but also of so-called near misses and
uncertain outcomes. The constructs we have outlined have the potential to be
applied internationally, across primary-care settings, to improve both the
detection and prevention of incidents that cause the most severe harm to
patients.
PMID- 29962553
TI - Early assessment of China's 2015 tobacco tax increase.
AB - In 2015, the Chinese government raised tobacco excise tax for the first time
since 2009. Changing from previous practice, the State Tobacco Monopoly
Administration raised its cigarette prices at the same time. We assessed the
early impact of the 2015 tax increase on cigarette prices, sales volumes, tax
revenue generation and the potential effect on prevalence of smoking in China.
Between 2014 and 2016, the retail price of cigarettes increased on average by
11%, with the cheapest category of cigarette brands increasing by 20%. The
average proportion of tax in the price of cigarettes rose from 51.7% to 55.7%.
Annual cigarette sales decreased by 7.8%, from 127 to 117 billion packs. The
increase in cigarette prices could be associated with a 0.2% to 0.6% decrease in
the proportion of adults smoking, representing between 2.2 and 6.5 million fewer
smokers. Tax revenues from cigarettes increased by 14%, from 740 to 842 billion
Chinese yuan between 2014 and 2016, reflecting an extra 101 billion Chinese yuan
in tax revenues for the government. The 2015 tax increase shows that tobacco
taxation can provide measurable benefits to both public health and finance in
China. The experience also highlights the potential for tobacco taxation to
contribute to China's broader development targets, including the sustainable
development goals and Healthy China 2030. Looking forward, this link to
development can be facilitated through multisectoral research and dialogue to
develop consistent cross-sectoral objectives for tobacco tax policy design and
implementation.
PMID- 29962554
TI - Preparation of Fac-Tris(2-Phenylpyridinato) Iridium(III).
PMID- 29962556
TI - Role of the Ocean's AMOC in setting the Uptake Efficiency of Transient Tracers.
AB - The central role played by the ocean's Atlantic Meridional Overturning
Circulation (AMOC) in the uptake and sequestration of transient tracers is
studied in a series of experiments with the GISS and MIT ocean circulation
models. Forced by observed atmospheric timeseries of CFC-11, both models exhibit
realistic distributions in the ocean, with similar surface biases but different
response over time. To better understand what controls uptake, we ran idealized
forcing experiments in which the AMOC strength varied over a wide range,
bracketing the observations. We found that differences in the strength and
vertical scale of the AMOC largely accounted for the different rates of CFC-11
uptake and vertical distribution thereof. A 2-box model enables us to quantify,
and relate uptake efficiency of passive tracers to AMOC strength and how uptake
efficiency decreases in time. We also discuss the relationship between passive
tracer and heat uptake efficiency, of which the latter controls the transient
climate response to anthropogenic forcing in the North Atlantic. We find that
heat uptake efficiency is substantially less (by about a factor of five) than
that for a passive tracer.
PMID- 29962555
TI - Thriving in midlife: The roles of childhood nurturance and adult defense
mechanisms.
AB - The current study examined whether reliance on more adaptive defense mechanisms
throughout early adulthood may help explain previously documented relationships
between childhood nurturance and better midlife functioning. Utilizing a unique
longitudinal study, data were from age 18 through midlife (age 63) on 135 males.
Childhood nurturance was assessed upon study entry and defense mechanism usage
was assessed throughout earlier adulthood. Percentage of 'engaging' (more
adaptive) vs. 'avoidant' (less adaptive) defenses mediated the relationship
between childhood nurturance and 3 midlife outcomes: participants' relationship
quality with their children, marriage stability, and maximum earned income.
Results suggest that greater childhood nurturance relates to more adaptive
defensive styles in early adulthood, which is then associated with healthier
midlife functioning at work and in relationships.
PMID- 29962557
TI - Monitoring Algal Blooms in drinking water reservoirs using the Landsat 8
Operational Land Imager.
AB - In this study, we demonstrated that the Landsat-8 Operational Land Imager (OLI)
sensor is a powerful tool that can provide periodic and system-wide information
on the condition of drinking water reservoirs. The OLI is a multispectral
radiometer (30 m spatial resolution) that allows ecosystem observations at
spatial and temporal scales that allow the environmental community and water
managers another means to monitor changes in water quality not feasible with
field-based monitoring. Using the provisional Land Surface Reflectance (LSR)
product and field-collected chlorophyll-a (chl-a) concentrations from drinking
water monitoring programs in North Carolina and Rhode Island, we compared five
established approaches for estimating chl-a concentrations using spectral data.
We found that using the 3 band reflectance approach with a combination of OLI
spectral bands 1, 3, and 5, produced the most promising results for accurately
estimating chl-a concentrations in lakes (R2 value of 0.66; RMSE value of 8.9 MUg
l-1). Using this model, we forecast the spatial and temporal variability of chl-a
for Jordan Lake, a recreational and drinking water source in piedmont North
Carolina and several small ponds that supply drinking water in southeastern Rhode
Island.
PMID- 29962559
TI - Measuring Patient-Reported Outcomes Adaptively: Multidimensionality Matters!
AB - As there is currently a marked increase in the use of both unidimensional (UCAT)
and multidimensional computerized adaptive testing (MCAT) in psychological and
health measurement, the main aim of the present study is to assess the
incremental value of using MCAT rather than separate UCATs for each dimension.
Simulations are based on empirical data that could be considered typical for
health measurement: a large number of dimensions (4), strong correlations among
dimensions (.77-.87), and polytomously scored response data. Both variable- (SE <
.316, SE < .387) and fixed-length conditions (total test length of 12, 20, or 32
items) are studied. The item parameters and variance-covariance matrix Phi are
estimated with the multidimensional graded response model (GRM). Outcome
variables include computerized adaptive test (CAT) length, root mean square error
(RMSE), and bias. Both simulated and empirical latent trait distributions are
used to sample vectors of true scores. MCATs were generally more efficient (in
terms of test length) and more accurate (in terms of RMSE) than their UCAT
counterparts. Absolute average bias was highest for variable-length UCATs with
termination rule SE < .387. Test length of variable-length MCATs was on average
20% to 25% shorter than test length across separate UCATs. This study showed that
there are clear advantages of using MCAT rather than UCAT in a setting typical
for health measurement.
PMID- 29962558
TI - REDUCTION OF PM2.5 TOXICITY ON HUMAN ALVEOLAR EPITHELIAL CELLS A549 BY TEA
POLYPHENOLS.
AB - Tea-derived polyphenols have anticancer and antioxidant properties, and they can
regulate oxidative stress. This study was designed to quantify both the toxic
effects of fine particulate matter with aerodynamic diameter less than 2.5 MUm
(PM2.5) and determine whether tea polyphenols could provide a protective effect
against PM2.5 toxicity on human alveolar epithelial A549 cells in vitro.
Cytotoxic effects of the PM2.5 on A549 cells were measured by means of cell
viability, the expression of caspase-3, bax/bcl-2 and C/EBP-homologous protein
(CHOP), and the generation of intracellular reactive oxygen species,
malondialdehyde and superoxide dismutase. The results showed that tea polyphenols
ameliorated some of the adverse effects of PM2.5 on A549 cell viability and
superoxide dismutase levels. In addition, tea polyphenols decreased the
production of reactive oxygen species, malondialdehyde generation, and apoptosis
in response to PM2.5 exposure. Therefore, our results support a role for tea
polyphenols in reducing the toxicity of PM2.5, particularly with regard to
targeting oxidative stress and apoptosis.
PMID- 29962560
TI - Eye-Tracking Based Attention Bias Modification (ET-ABM) Facilitates Disengagement
from Negative Stimuli in Dysphoric Individuals.
AB - To address shortcomings of purely reaction-time based attention bias modification
(ABM) paradigms, a novel eye-tracking based ABM training (ET-ABM) was developed.
This training targets the late disengagement from negative stimuli and the lack
of attention for positive information, which are characteristics of depression.
In the present study, 75 dysphoric students (BDI >= 9) were randomly assigned to
either this positive training (PT), or a sham-training (ST) that did not train
any valence-specific gaze pattern (positive and negative pictures had to be
disengaged from and attended to equally often). Results showed that the PT
induced a positive attentional bias (longer fixations of positive than negative
pictures). Although the ST group showed an increase in positive attentional bias
as well, this increase was not as strong as in the PT group. Compared to the ST,
the PT specifically induced faster disengagement from negative pictures. No
differential training effects were found on stress responses or state rumination.
These results show that the ET-ABM successfully modifies attentional processes,
specifically late disengagement from negative stimuli, in dysphoric students, and
hence might be a promising alternative to existing ABM paradigms.
PMID- 29962561
TI - Vocal dialects in parrots: patterns and processes of cultural evolution.
AB - Vocal dialects have fascinated biologists for over 50 years. This mosaic pattern
of geographic variation in learned vocalizations was first described in a
songbird, and since that time, most studies investigating dialects have focused
on songbird species. Here we examine patterns of geographic variation in the
calls of a different group of vocal learning birds, the parrots (Order
Psittaciformes). We summarize the growing literature on vocal variation in
parrots, and complement this review with a survey of variation in the genus
Amazona using calls from sound libraries. We find strikingly similar patterns to
those previously found in songbirds. Over 90% of parrots examined in the
literature, and 69% of Amazona species surveyed, showed geographic variation
consistent with a propensity to share local call types. This trait is
evolutionarily labile and widespread; within Amazona most clades contained
species with and without geographic variation, and most major lineages of parrots
include representatives with dialects. We found little support for the long
standing hypothesis that dialects isolate populations and thus generate genetic
differences among populations. Instead, most studies support the idea that
dialects are maintained by social benefits of matching local call types, a
finding that has implications for the management of captive and endangered
populations. Considerable scope remains for studies that experimentally test
hypotheses for the exact nature of these benefits, as well as studies that employ
comparisons among species, to understand how the interplay between ecology,
social dynamics and vocal learning capacities produces different patterns of
variation across the parrots.
PMID- 29962562
TI - UNHEALTHY WEIGHT IN INDIAN FAMILIES: THE ROLE OF THE FAMILY ENVIRONMENT IN THE
CONTEXT OF THE NUTRITION TRANSITION.
AB - India faces a dual burden of increasing obesity and persistent underweight as it
experiences the nutrition transition-the dietary and lifestyle changes that
accompany globalization, economic development, and technological change. Yet, the
nutrition transition is not solely a top-down process; rather, global forces
converge with local practices at multiple levels of the social ecology. The
family environment, a key site for the transmission of local customs and norms,
remains largely unexplored in India. We examined the extent to which opposite
gender siblings and mother-child pairs were concordant or discordant in body
weight, and whether domains of the family environment, specifically, food
practices, food-related gender norms, and household resources, were associated
with patterns of unhealthy weight within and between families. Multilevel dyadic
analysis and logistic regression were conducted using survey data from a
representative sample of 400 families in a Southern Indian city. We identified
substantial clustering of weight among opposite-gender sibling pairs (ICC=0.43)
and mother-child pairs, as well as important patterns of discordance, including
11% of families experiencing a dual burden of underweight and overweight.
Household resources, including mother's education and income, were salient in
explaining the distribution of body weight within and between families.
Importantly, less examined domains of the family environment were also relevant,
including food practices (e.g. grocery shopping frequency), and food-related
gender norms (e.g. mother's control of food served at home). Continued
exploration of how global and local practices converge in households will be
necessary to develop programming that effectively addresses India's dual burden
of unhealthy weight.
PMID- 29962563
TI - Detection of Lane-Change Events in Naturalistic Driving Videos.
AB - Lane changes are important behaviors to study in driving research. Automated
detection of lane-change events is required to address the need for data
reduction of a vast amount of naturalistic driving videos. This paper presents a
method to deal with weak lane-marker patterns as small as a couple of pixels
wide. The proposed method is novel in its approach to detecting lane-change
events by accumulating lane-marker candidates over time. Since the proposed
method tracks lane markers in temporal domain, it is robust to low resolution and
many different kinds of interferences. The proposed technique was tested using
490 h of naturalistic driving videos collected from 63 drivers. The lane-change
events in a 10-h video set were first manually coded and compared with the
outcome of the automated method. The method's sensitivity was 94.8% and the data
reduction rate was 93.6%. The automated procedure was further evaluated using the
remaining 480-h driving videos. The data reduction rate was 97.4%. All 4971
detected events were manually reviewed and classified as either true or false
lane-change events. Bootstrapping showed that the false discovery rate from the
larger data set was not significantly different from that of the 10-h manually
coded data set. This study demonstrated that the temporal processing of lane
markers is an effcient strategy for detecting lane-change events involving weak
lane-marker patterns in naturalistic driving.
PMID- 29962564
TI - Mental Healthcare Act 2017: Liberal in Principles, Let Down in Provisions.
PMID- 29962565
TI - The Phenomenon of Family Suicides: An Explorative Study into Consecutive 32
Incidents in Kerala.
AB - Background: Suicides rank high as the cause of human deaths. But research on
whole family ending life is scanty. This study explored the family suicides in
Kerala. Methodology: All the family suicides reported from four central districts
of Kerala State during the year 2000 were included. Cases were prospectively
located from different sources. A research associate systematically gathered
information, from survivors, family and key persons in the locality. Results: 84
lives lost in 32 incidents involving 99 persons. No report from Muslim dominated
district. Largest age group was 19 and below, others progressively decreased.
Poisoning formed most frequent method; drowning, burns, hanging and wrist
slashing followed. Suicide notes were left in half. Mental illness and physical
illness were noted in five and eight incidents respectively. Financial crisis
reported as the main reason. The SES of the deceased and their parents were same
but half of the families were leading a life at a higher level than could be
afforded. Warning signals noted in 12 incidents. Decision was taken by father and
mother (17), mother (10) or father alone (5). The incidents came to the attention
of others without long delay. Discussion: Firm stand of the religion against
suicides on individual reasons could explain absence of family suicides from
Muslim dominated district. Selection of sure method and flawless execution
explains high lethality. Presence of victims explains more loss of young lives
and profile difference from reported suicide attempts. Opening up of avenues for
higher dreaming due to globalisation and wider visual media could be a reason for
living unaffordable standard of life and resulting financial difficulty. The
warning signals were recognised, but not responded by others. Social support was
strong within the family but was non-existing with outside. Strong social support
could be pathological if it is narrow.
PMID- 29962566
TI - Psychometric Properties of the Insight in Psychosis Questionnaire and its
Correlation to Psychopathology in Indian Population.
AB - Background: The present study attempted to standardize insight in psychosis
questionnaire in India and correlate insight with psychopathology and
functioning. Materials and Methods: A cross-sectional study was conducted in July
and August 2016. The questionnaire was translated into Hindi following standard
procedure. After ensuring that the patients fulfilled criteria for the study,
consent was taken, and insight in psychosis questionnaire (Hindi version),
positive and negative syndrome scale for schizophrenia, clinical insight rating
scale, Present State Examination insight item, and the global assessment of
functioning scale were applied. Appropriate statistical analyses were done.
Results: The mean age of 53 patients included in the study was 33.42 +/- 10.32
years. The majority of the patients were males, single and had <12 years of
formal education and resided in joint families and urban areas. The mean duration
of illness was 78.64 +/- 86.16 months. The insight in psychosis questionnaire was
found to have good internal consistency, split-half reliability, test-retest
reliability, and convergent validity in the Indian population. Patients residing
in the rural background had lower insight than those residing in urban areas, and
patients having brief psychotic disorder had lower insight than those having
schizophrenia. Insight was positively correlated with negative symptoms, general
psychopathology, and total psychopathology but negatively correlated with
positive symptoms. Psychopathology was negatively correlated with functioning.
Conclusions: The study of insight and its correlation with psychopathology and
functioning should be an important area for research as insight is associated
with outcome and prognosis among patients with psychosis.
PMID- 29962567
TI - Polycystic Ovary Syndrome in Bipolar Affective Disorder: A Hospital-based Study.
AB - Background: Preliminary studies suggest a multidimensional relationship of mood
pathology with endocrine disturbances. Studies have found an increased risk of
mood disorders in polycystic ovary syndrome (PCOS), and conversely, many of the
medications commonly used in the treatment of bipolar affective disorder (BPAD)
can have deleterious effects on blood levels of reproductive hormones and
consequently on the hypothalamic-pituitary-gonadal (HPG) axis and reproductive
function. Furthermore, there is evidence of reproductive dysfunction in women
with BPAD before treatment. Objectives: To assess the comorbidity of PCOS in
patients of BPAD and to study risk factors associated with this comorbidity.
Materials and Methods: Two hundred female patients with the Diagnostic and
Statistical Manual of Mental Disorders, 4th Edition diagnosis of BPAD, between
ages of 15 and 45 years, were evaluated by an endocrinologist. Patients reporting
menstrual disturbances or having any stigmata of PCOS were further subjected to
hormonal analysis, which included luteinizing hormone, follicle-stimulating
hormone, prolactin, and testosterone, in the early follicular phase of menstrual
cycle. Diagnosis of PCOS was made as per the NIH criteria. Results: Of 200
patients, 46 (23%) were diagnosed as having PCOS. Forty-five percent (n = 90)
reported menstrual disturbances while 27% (n = 54) had polycystic ovaries on
ultrasonography. 19.2% of the patients diagnosed as PCOS had a history of
valproate intake while 27.90% patients had no such history (P = 0.15). No
significant difference (P = 0.07) was found in the prevalence of PCOS among
various drug groups (including group on multiple mood stabilizers). Conclusion: A
higher prevalence of PCOS is seen in BPAD, irrespective of pharmacotherapy,
suggesting a common link between the disorders which might be in the form of
disturbance in HPG axis.
PMID- 29962568
TI - Psychiatric Burden in the Morbidly Obese in Multidisciplinary Bariatric Clinic in
South India.
AB - Background: Obesity is a global epidemic. Bariatric surgery is being considered
as the treatment of choice in morbid obesity. Psychiatric comorbidity affects
outcomes in this population. There is a dearth of data on psychiatric profile of
the morbidly obese from Indian subcontinent. We studied people with morbid
obesity to estimate the psychiatric burden among them and to identify factors
associated for developing psychiatric disorders. Methodology: This is a cross
sectional study done in a bariatric clinic of a tertiary care teaching hospital
in South India. Sixty morbidly obese patients were evaluated by psychiatrists and
data from medical records were collected and analyzed. Prevalence of psychiatric
disorders was estimated. They were compared with patients without psychiatric
disorders using appropriate statistical tests. Results: Nearly 33.33% of the
patients had a psychiatric disorder. Depression and dysthymia accounted for about
half of those cases. The variables that were associated with psychiatric
disorders were current suicidal ideation, past self-injurious behavior, perceived
poor social support, and past psychiatric history. Conclusion: One-third of the
morbidly obese patients having psychiatric disorder is suggestive of high
comorbidity. Considering this active involvement of psychiatrists in bariatric
clinic would be useful.
PMID- 29962569
TI - Instrumental Activities of Daily Living Dysfunction among People with
Schizophrenia.
AB - Background: Life skills are the basic skills that are needed to live
independently and that support meaningful, productive roles. The negative
symptoms and cognitive dysfunction seen in schizophrenia may lead to
deterioration in the life skills of the patient. The assessment of current life
skills of the patient and subsequent intervention becomes necessary for
comprehensive rehabilitation of people with mental illness. This study attempted
to assess the instrumental activities of daily living among people with
schizophrenia in India. Methods: One hundred consecutive patients with
schizophrenia, between 18 and 60 years, who presented to a tertiary psychiatric
facility were assessed using (i) Lawton instrumental activities of daily living
scale (LIADL), (ii) positive and negative symptom scale (PANSS), (iii) pro forma
for sociodemographic and clinical characteristics. Results: The majority of the
patients were male, young adults, married, with secondary school education,
middle socioeconomic status, from nuclear families, unemployed and were diagnosed
to have paranoid schizophrenia. The reported IADL dysfunction included
difficulties in handling medications (86%), preparing food (85%), shopping (78%),
handling finances (61%), doing laundry (52%), housekeeping (47%), using public
transport (32%), and using telephones (5%). The dysfunction documented differs
from that reported in the west. Total PANSS score (P = 0.015) and its general
psychopathology subscale (P = 0.005) correlated inversely with the total LIADL
score; PANSS scores and sociodemographic variables were associated with some
subscales of LIADL. Conclusions: IADL dysfunction, common in people with
schizophrenia, demands detailed assessment, and tailored training to ensure
optimum functioning.
PMID- 29962570
TI - Role of Novel Dietary Supplement N-acetyl Cysteine in Treating Negative Symptoms
in Schizophrenia: A 6-Month Follow-up Study.
AB - Background: Abnormal metabolism of dopamine and glutamate in schizophrenia
induces oxidative stress that is exacerbated by brain glutathione (GSH)
deficiency. N-acetyl cysteine (NAC) increases brain GSH levels and is being used
as an adjunctive agent in patients with schizophrenia. This open-label
exploratory study in a naturalistic setting was conceived to examine the efficacy
of NAC augmentation in treating negative syndrome in schizophrenia. Aims: To
examine the efficacy of add-on NAC (1200 mg) in treating negative symptoms
measured using Scale for the Assessment of Negative Symptoms (SANS) and clinical
global impression (CGI) at baseline and 24 weeks. Subjects and Methods: In a 24
week feasibility study with open-label design, thirty patients with the
International Classification of Diseases-Tenth Edition diagnosis of schizophrenia
were recruited. Eligible patients were required to have been treated with stable
dose of clozapine or amisulpride for negative symptoms for a minimum period of 8
weeks were selected for the study. The subjects were assigned to receive NAC (1.2
g/day) as an add-on treatment. Severity of negative symptoms was measured using
SANS and CGI-severity at baseline and improvement with NAC measured using CGI
improvement at 24 weeks. Serum interleukin-6 was assessed before NAC initiation
at baseline. Results: NAC augmentation showed a significantly greater improvement
in negative symptoms on total SANS and CGI scores at 24 weeks. Conclusions: NAC
may be effective as an adjunct for the treatment of negative symptoms in
schizophrenia.
PMID- 29962571
TI - Demographic and Clinical Correlates of Social Cognition in Schizophrenia:
Observation from India.
AB - Purpose: Although deficits in social cognition (SC) had been recognized as a
hallmark of schizophrenia, quality data in Indian context were limited. The
purpose of the current research was to determine the demographic and clinical
correlates of SC in schizophrenia. Methods: Between February 2014 and January
2015, a case-control study was conducted in Chhattisgarh, India, among 100
paranoid schizophrenia patients (ICD-10) from two psychiatric hospitals and 100
neighborhood-based healthy (28-item General Health Questionnaire) controls. After
obtaining signed consent, SC was assessed among 20-35-year-old, high school or
more educated subjects ensuring eligibility for appropriate scales. Results:
Patients had poorer social knowledge (adjusted-beta-coefficient [AC] = -4.89 [
6.32, -3.45]) and lower predicted mean score for internal attribution of negative
event (AC: -0.72 [-1.17, -0.27]). Nonrecognition of facial expressions especially
for anger (adjusted-odds-ratio [AOR] = 3.50 [1.17, 10.51]), surprise (AOR = 2.91
[1.36, 6.25]) and fear (AOR = 2.35 [1.11, 5.01]) was more common among cases.
Wrong recognition of expressions was less likely among females (for surprise: AOR
= 0.35 [0.13, 0.93]) and educated (for sadness: AOR = 0.11 [0.02, 0.58]) but more
common among wealthy (for surprise: AOR = 4.58 [1.22, 17.19]) and urban (for
fear: unadjusted odds ratios = 4.30 [1.53, 12.03]) subjects. If recognized
expressions correctly, females were more likely to perceive higher intensity of
anger (AOR = 4.30 [1.80, 10.29]) and happiness (AOR = 4.22 [1.66, 10.72]). Higher
intensity was perceived by more educated subjects regarding anger (AOR = 2.57
[1.04, 6.34]) but not for happiness (AOR = 0.09 [0.01, 0.79]).
Unmarried/divorced/separated perceived happiness (AOR = 2.86 [1.02, 7.97]) with
more intensity while those in joint families perceived sadness (AOR = 2.80 [1.22,
6.41]) and fear (AOR = 2.28 [1.01, 5.16]) with more intensity. Conclusion: A
significant impairment in SC was observed among paranoid schizophrenia cases in
Chhattisgarh, India. Intervention and further research addressing identified
issues of SC need to target specific subpopulations, among schizophrenia
patients.
PMID- 29962572
TI - Burnout in Indian Psychiatrists.
AB - Background: Individuals associated with service providing and decision-taking are
prone for stress leading to burnout. Aim: The aim of this study is to find out
the details of burnout among Psychiatrists in India. Materials and Methods:
Copenhagen Burnout Inventory (CBI) with structured biodata sheet was sent to the
representative sample of psychiatrists by e-mail. Basic statistical analysis was
done to find out prevalence, analyze response pattern, and differences between
those with and without burnout. Results: The number of psychiatrists that
responded to survey was 110-81 (74%) male and 29 (26%) female. The number of
burnout cases in one or other spheres was 51 in 35 psychiatrists accounting for
the prevalence of 46%. 32% of psychiatrists have burnout. Four psychiatrists have
burnout in all three dimensions, nine in two dimensions, and 22 in one dimension.
Personal burnout topped in the three dimensions (63%) followed by work burnout
(24%). Patient burnout was least at 14%. Conclusions: Burnout, though not very
high, is to be taken seriously by Indian psychiatrists and protective and
preventive measures are in order.
PMID- 29962573
TI - A Descriptive Study on Behavioral and Emotional Problems in Orphans and Other
Vulnerable Children Staying in Institutional Homes.
AB - Introduction: Orphans and the other vulnerable children and adolescents (OVCA)
living in institutional homes are more prone to behavioral and emotional problems
than others as they are deprived of a family's love and care. There is a dearth
of studies focusing on the psychological health of these children in India.
Hence, we have conducted a cross-sectional descriptive study to explore the
behavioral and emotional problems in these institutionalized children. Materials
and Methods: The sample consisted of 292 orphans and OVCA in institutional homes
of Visakhapatnam city. The sociodemographic data were collected using a semi
structured questionnaire. The Strengths and Difficulties Questionnaire (SDQ) with
impact supplement was used to assess the behavioral and emotional problems in
them. Results: In our study, 49 (16.78%) out of 292 children and adolescents were
found to be having behavioral and emotional problems. Factors such as age, sex,
reason for being in the institute, age of admission, and years of stay in the
home were all seen to be significantly associated (P < 0.05) with emotional and
behavioral problems. Conduct problems (34.90%) were found to be most prevalent
followed by peer problems (15.80%), emotional problems (14.70%), hyperactivity
(8.60%), and low prosocial behavior (3.40%). Conclusion: The present study shows
that the orphans and OVCA in institutional homes are vulnerable to behavioral and
emotional problems. The screening for conduct problems, emotional problems,
hyperactivity, and peer problems needs to be done at a regular basis for these
children. Given the paucity of data in this regard, several multicenter studies
also need to be done to get an overall comprehensive view of these problems.
PMID- 29962574
TI - Delirium in Intensive Care Unit: Phenomenology, Subtypes, and Factor Structure of
Symptoms.
AB - Aim: This study aimed to explore the phenomenology, motor subtypes, and factor
structure of symptom profile of delirium in patients admitted to the intensive
care unit (ICU). Methods: Consecutive patients aged >=16 years admitted in an ICU
were screened daily for delirium using confusion assessment method-ICU. Patients
diagnosed to have delirium as per Diagnostic and Statistical Manual fourth
revision, text revision (DSM-IVTR) criteria were assessed with Delirium Rating
Scale-Revised 98 (DRS-R 98) and Memorial Delirium Assessment Scale (MDAS). Motor
subtypes of delirium were assessed with amended Delirium Motor Symptom Scale.
Results: Sixty-six patients were evaluated for delirium, of which 45 (68%)
patients developed delirium at point of their ICU stay. All patients had sleep
wake cycle disturbances, followed by motor symptoms (retardation - 80%; agitation
- 73.3%). As per MDAS assessment, all the subjects had disturbances in the
consciousness and sleep-wake cycle disturbances, and a substantial majority also
had attention difficulties (93.3%) and motor symptoms (93.3%). Hypoactive subtype
(47%) was the most common motoric subtype of delirium. Factor analysis revealed
three-factor model for DRS-R 98, MDAS, and combining items of the two.
Conclusion: Phenomenology of delirium in ICU setting is similar to that of the
non-ICU settings. The factor analysis consistently demonstrated a three factor
solution, with a robust attention-arousal factor, and overlapping cognitive (core
vs. non-core) motor factors.
PMID- 29962575
TI - Blue Whale Challenge: Perceptions of First Responders in Medical Profession.
AB - Context: Blue Whale Challenge is a phenomenon which gained its early foothold on
the internet chatboards. It is a dare-based harmful game which has a list of
fifty tasks which you perform culminating in one's death on the final task. The
fatalities caused by individuals playing this game have been reported first in
Russia and followed by at least twenty countries reporting it, including India.
Aims: This study was conducted to assess perceptions and knowhow of the first
responders in medical profession about online challenges. Settings and Design:
This was a cross-sectional descriptive study. Subjects and Methods: Fifty-four
medical professionals who practice either psychiatry, clinical psychology, or
pediatrics were interviewed using a semi-structured open-ended survey was
administered and data were obtained. Statistical Analysis Used: Descriptive
statistics was used. Results: Thirty-five (65%) of the total participants have
heard about the Blue Whale Challenge but lacked further knowledge about the game.
Ten percent of total participants knew about other internet challenges. Only 26%
of total participants were largely aware about the details and harmful nature of
the game. Only 12 (22%) participants knew the signs to identify the children
playing this game. None of the practitioners reported of having encountered any
parent or child enquiring or reporting this in their practice at the time of
conducting the survey. Conclusions: The medical fraternity is lagging behind in
updating themselves of the online phenomena which are important for the better
outcome of children presenting with participation in online challenges. The
nature of the game has been discussed, and guidelines for identifying vulnerable
population have been put forward.
PMID- 29962576
TI - Safe Administration of Electroconvulsive Therapy in Patient with Ventricular
Septal Defect Patch: A Rare Case Report.
AB - Electroconvulsive therapy (ECT) is a safe and effective treatment for many
psychiatric illnesses. Even in cardiac patients, it is a low-risk procedure as
compared to chronic use of the medications with possible side effects. Although
rare, cardiovascular events during ECT remain a principal cause of morbidity and
mortality. Therefore, administration of ECT in cardiac patients remained
questionable. There is no data regarding the safety of ECT administration in
patients with repaired ventricular septal defect (VSD), and to the best of our
knowledge, this is the first case report of safe administration of ECT in patient
with VSD. In this case report, we describe a patient with bipolar affective
disorder, with repaired VSD, who was safely and successfully treated with ECT. It
is essential that appropriate cardiac management be provided before, during, and
after ECT by a multidisciplinary team of psychiatrists, cardiologists, and
anesthesiologists. This case report suggests that ECT can be safely given to
patients with repaired VSD, wherever there is an absolute indication for ECT.
PMID- 29962577
TI - Personality Changes in Bilateral Superior Frontal and Parafalcine Frontoparietal
Polymicrogyria: A Rare Case Report.
AB - Polymicrogyria is a neurodevelopmental abnormality which results in the formation
of excessive, small, abnormal, partially fused gyri with superficially located
sulci replacing the normal gyral pattern. Intellectual disability, global
developmental delay, epilepsy, language deficits, and motor deficits are commonly
reported in patients with polymicrogyria. We present here the case of a young
male with a rare pattern of bilateral superior frontal and parafalcine
frontoparietal polymicrogyria, who had a mild intellectual disability,
intractable seizures along with personality changes. This case report also
highlights the relevance of neuroimaging in such cases, possible explanations of
personality change in polymicrogyria and relevant management issues with a review
of the literature.
PMID- 29962578
TI - Acute-onset Orofacial Dyskinesia with a Single Low Dose of Oral Flupentixol: A
Case Report.
AB - Tardive dyskinesia are known to occur commonly among patients receiving
neuroleptic drugs for prolonged periods. But, few reports of acute onset
dyskinesia have also been reported in the literature. This report highlights one
such case where the patient had dyskinetic movements with a single low dose of
oral Flupentixol. Further, we examine the potential nosological status of acute
onset dyskinesia associated with neuroleptic use.
PMID- 29962579
TI - Lurasidone Induced Thrombocytopenia: Is it a Signal of Drug Induced
Myelosuppression?
AB - The U.S. Food and Drug Administration (FDA) has approved a supplemental new drug
application Lurasidone (Latuda, Sunovion Pharmaceuticals), an atypical
antipsychotic, for the treatment of schizophrenia in adolescents 13-17 years of
age. Lurasidone was previously indicated in the U.S. for the treatment of adults
with schizophrenia and major depressive episodes with bipolar I disorder as
monotherapy. We present a case of a 29-year-old male patient who was hospitalized
with thrombocytopenia (WHO grade-3 toxicity) (unlabeled) along with
extrapyramidal disorder, gastritis, and hyperprolactinemia within 2-3 months of
initiation of tablet lurasidone 80 mg/day (Lurasid, Intas Pharmaceuticals) in
bipolar depression. Dechallenge was found to be positive in three reactions
except hyperprolactinemia (outcome unknown) during hospital stay. The terms
anemia and leukopenia are well labeled/listed with the drug literatures of
lurasidone. Thus, this case presents a strong probability of lurasidone to cause
myelosuppression/bone marrow depression.
PMID- 29962580
TI - A Comment on "Prevalence and Factors Associated with Depression among Clinically
Stable People Living with HIV/AIDS on Antiretroviral Therapy".
PMID- 29962581
TI - Authors' Response to Comments on "Prevalence and Factors Associated with
Depression among Clinically Stable People Living with HIV/AIDS on Antiretroviral
Therapy.
PMID- 29962582
TI - A Comment on "Perceptions of Accredited Social Health Activists on Depression: A
Qualitative Study from Karnataka, India".
PMID- 29962583
TI - Authors' Reply to Comments on ASHAs' Perceptions on Depression.
PMID- 29962584
TI - Cabell's Blacklist: A New Way to Tackle Predatory Journals.
PMID- 29962585
TI - Erratum: Validation of a Screening Tool for Learning Disorder in Children.
AB - [This corrects the article on p. 737 in vol. 39, PMID: 29284803.].
PMID- 29962586
TI - Effect of Using Ringer's Lactate, with and without Addition of Dextrose, on Intra
Operative Blood Sugar Levels in Infants Undergoing Facial Cleft Surgeries.
AB - Background: Addition of glucose in the intraoperative fluid is a routine practice
in infants. Under general anesthesia, due to neuroendocrine stress response, this
could result in overt hyperglycemia. Aims: The aim of this study was to find
whether the addition of 2% dextrose to Ringer's lactate (RL) caused hyperglycemia
compared to no addition of dextrose to RL. Settings and Designs: This prospective
randomized study was conducted in 100 infants undergoing facial cleft surgery at
a tertiary care institution. Subjects and Methods: Group D received RL with 2%
dextrose and Group R received RL without the addition of dextrose. Blood sugars
were measured at induction, 1 h and 2 h later. Hyperglycemia was defined as blood
sugar >150 mg/dL and hypoglycemia as <70 mg/dL. Statistical Analysis Used:
Pearson's Chi-square test, Paired t-test, Mann-Whitney test, and Independent
sample t-test were used as applicable. Results: Baseline blood sugar was
comparable in both groups. A significant increase in blood sugar values from
baseline was seen in both groups, but the increase was significantly more in
Group D at 60 min (136.5 +/- 41.9 vs. 109.2 +/- 20.5) and at 120 min (150.1 +/-
45.5 vs. 123.1 +/- 31.7). The incidence of hyperglycemia was 50% in Group D and
12% in Group R. No patient developed hypoglycemia intraoperatively. No
significant correlation between blood sugar and hours of fasting was established.
Conclusion: Routine addition of dextrose to RL is not essential during short
surgeries under general anesthesia in infants, provided preinduction blood sugar
level is >70 mg/dL and intraoperative sugars are periodically monitored.
PMID- 29962587
TI - Assessment of Job Satisfaction and Quality of Life among Practicing Indian
Anesthesiologists.
AB - Introduction: Anesthesiologists are exposed to extreme level of stress from
beginning of career. With evolution of super-specialty branches, level of stress
faced has also raised. Prolonged working hours, poor hospital facilities and
dependencies on surgeon are main contributing factors. Stress and unsatisfactory
remuneration may lead to decrease in job satisfaction. One should have a good
quality of life, but high level of stress may itself compromise quality of life.
This study aims at assessment of stress, quality of life spent, job satisfaction,
and health issues. Aim: The aim is to study stress level, job satisfaction, and
quality of life of practicing Indian anesthesiologists. Setting and Design: This
was an online survey, descriptive study. Subjects and Methods: An online survey
consisting of 21 questions was sent to Indian anesthesiologists by E-mail using
SurveyMonkey platform. The responses were collected and analyzed. Results: Out of
1219 anesthesiologists, 81% were satisfied being anesthesiologist, but 58% are
unsatisfied with remuneration. More than one role was played by 47.7% of
anesthesiologists. Nearly 83% of anesthesiologists agreed that the stress is
highest among anesthesiologist compared to other medical professionals. Stress
does reduce with the presence of another anesthesiologist while managing cases.
Most anesthesiologists practiced various stress reduction methods of which
spending time with the family was most popular method. Conclusion: This study
divulges working pattern, job satisfaction, level of stress faced, methods to
alleviate stress, and quality of life of anesthesiologists in India. A balanced
family and professional life with proper utilization of leisure will reduce the
stress.
PMID- 29962588
TI - Clonidine as a Sole Epidural Adjuvant in Combined Spinal-epidural: Clinical
Study.
AB - Background and Aims: Clonidine has been used as an epidural adjuvant along with
local anesthetics; however, its use as a sole epidural adjuvant in combined
spinal-epidural (CSE) anesthesia has not been explored; thus, this study aimed to
assess the effects of clonidine as a sole epidural adjuvant in CSE on sensory and
motor characteristics of 0.5% hyperbaric bupivacaine given by subarachnoid route.
Methodology: A total of 60 patients belonging to the American Society of
Anesthesiologists Classes I and II aged 18-60 years were randomized in two
groups; group G300 and group GNS. G300 group received 300 mg clonidine and GNS
received normal saline through epidural route followed by 15 mg of 0.5%
hyperbaric bupivacaine as subarachnoid block. Onset of sensory block (time to
T10) and motor block (time to Bromage 3), level of sedation (using Modified
Ramsay Sedation Score), and hemodynamic changes were recorded. Two-segment
regression, duration of analgesia (time for 1st rescue analgesia), and motor
block (time to Bromage 0) were recorded. Student's t-test (two-tailed,
independent) and Chi-square/Fisher's exact probability test were used for
statistical analysis. Results: The demographic data were comparable between the
groups. The onset of sensory and motor block was significantly faster in G300
(sensory-71.63 +/- 4.51 s, motor-55.63 +/- 2.54 s) as compared to GNS (sensory
90.13 +/- 4.88 s, motor-118.43 +/- 9.50 s) (P < 0.001 and < 0.001, respectively).
The two-segment regression was 199.33 +/- 19.11 min and 79 +/- 9.77 min in G300
and GNS, respectively, (P < 0.001). Duration of analgesia was 317.90 +/- 15.32
min and 207 +/- 20.66 min for G300 and GNS, respectively (P < 0.001), and
duration of motor block was 409.9 +/- 34.87 min and 204 +/- 22.79 min for G300
and GNS, respectively (P < 0.001). The side effects such as hypotension and
bradycardia were statistically and clinically not significant. Conclusion:
Clonidine used as a sole epidural adjuvant in dose of 300 mg, for infraumbilical
surgeries, has significantly faster onset of sensory and motor block with
prolonged duration of analgesia and motor blockade and no significant side
effects on a conventional subarachnoid block performed with 0.5% hyperbaric
bupivacaine.
PMID- 29962589
TI - The Effect of Single-dose Intravenous Dexamethasone on Postoperative Pain and
Postoperative Nausea and Vomiting in Patients Undergoing Surgery under Spinal
Anesthesia: A Double-blind Randomized Clinical Study.
AB - Background: The use of neuraxial anesthesia has dramatically increased. Acute
postoperative pain is an undesirable outcome that can delay functional recovery
for patients undergoing surgery. Nausea and vomiting in the postoperative period
occurs in 20%-30% of the patients and together are the second-most common
complaint reported (pain is the most common). Efficacy of glucocorticoids for
reducing pain and inflammation after surgery is being explored. Glucocorticoids
are strong anti-inflammatory agents, which can be used for a short-time
postoperative pain control in various surgeries. Dexamethasone is a
glucocorticoid with little mineralocorticoid effect commonly used perioperatively
to reduce postoperative nausea and vomiting (PONV) and has a beneficial role in
postoperative analgesia. Dexamethasone has also an antiemetic effect, in addition
to its anti-inflammatory and analgesic effects. Aim: The main purpose of this
study is to evaluate the effect of administration of single-dose intravenous
(i.v.) dexamethasone on postoperative pain and PONV in patients undergoing
surgery under spinal anesthesia. Settings and Design: A double-blind randomized
clinical study was performed in our institute between November 2014 and October
2015 after obtaining clearance from the ethical committee. Materials and Methods:
A double-blind randomized clinical study was performed on 60 patients posted for
surgery under spinal anesthesia. Patients were randomly assigned into two groups:
A (study: 2 ml [8 mg] dexamethasone) and B (control: 2 ml saline). In both the
groups, variables such as mean arterial blood pressure (MAP), heart rate (HR),
respiratory rate, severity of pain (based on visual analog scale), and other
symptoms such as nausea and vomiting were recorded at different time points
during the first 24 h after surgery. Statistical methods using Student t-test
(two-tailed, independent) and Fischer's exact test were used for analyzing the
data. Results: Between-group comparisons indicated significant differences in
terms of severity of postoperative pain and PONV (P < 0.001), MAP (P = 0.063),
and HR (P = 0.071), which in the study group were lower than the control group.
Conclusion: i.v. dexamethasone is efficient in reducing postoperative pain,
requirement of rescue analgesia on the first postoperative day, and incidence of
PONV with no significant changes in vital signs.
PMID- 29962590
TI - Correlation between Weight of the Baby and the Level of Sensory Blockade in
Spinal Anaesthesia for Caesarean Section: An Observational Study.
AB - Background: The spread of local anaesthetics during spinal anaesthesia is
affected by various factors and can be unpredictable especially in parturients
undergoing caesarean section. Factors like abdominal girth, symphysis fundal
height etc have to studied to know their impact on level of sensory blockade. We
hypothesized a study to find any correlation between weight of the baby and the
level of sensory blockade. Methods: 46 parturients posted for elective caesarean
section belonging to American Society of Anaesthesiologists (ASA) physical status
1 and 2 were included in the study. Maternal height and weight were noted down
before entering operation theatre. All patients were instituted subarachnoid
block with 2 cc of 0.5% of hyperbaric bupivacaine in sitting position. Level of
sensory blockade was assessed with pin prick along midline of the patient every
min till 5th minute and 5 minutes till 15th minute. The birth weight of baby was
recorded soon after delivery. Results: The weight of the baby and height of the
mother were correlated with the sensory blockade of T4. The number of babies
weighing more than 3.5 kgs were 3 in our study out of which 2 babies were
associated with maximum sensory blockade at 15th minute. It amounts to 66.7% when
compared with 14.7% in babies weighing 2.5 to 3.5 kgs which is suggestive of
significance ('P' value of 0.093). Conclusion: There is no statistically
significant correlation between weight of the baby and the level of sensory
blockade.
PMID- 29962592
TI - Intrathecal Bupivacaine with Neostigmine and Bupivacaine with Normal Saline for
Postoperative Analgesia: A Cost-effective Additive.
AB - Context: In day-to-day practice, subarachnoid block remains the most common type
of anesthesia. Bupivacaine is commonly used local anesthetic of neuraxial
blockade, though earlier 5% xylocaine and now ropivacaine and levobupivacaine are
also used. Additives such as opioids and alpha2 agonists are also used. We are
using neostigmine as an additive with bupivacaine to see the duration of
postoperative analgesia. Aims: To compare the efficacy of intrathecal hyperbaric
bupivacaine with neostigmine when compared to hyperbaric bupivacaine with normal
saline with regard to time of onset and duration of sensory and motor blockade,
time to two-segment regression. Settings and Design: Randomized, double-blinded
study. Subjects and Methods: One hundred patients admitted for lower abdominal
and lower limb surgeries done under spinal anesthesia (SA) during the period of
February 2015-August 2016. Statistical Analysis Used: Data were entered into
Microsoft excel data sheet and analyzed using SPSS 22 version. Categorical data
were represented in the form of frequencies and proportions. Chi-square was used
as a test of significance. Continuous data were represented as a mean and
standard deviation. Independent t-test was used as a test of significance to
identify the mean difference between two groups. Results: Mean onset of sensory
blockade with neostigmine group was 174.1 +/- 107.1 s and in normal saline group
171 +/- 35.6 s. Mean onset of motor blockade with neostigmine group was 197.4 +/-
111.6 s and in normal saline group was 219.4 +/- 73.2 s. Mean two-segment
regression with neostigmine group was 110.6 +/- 22.7 s and in normal saline group
was 71.5 +/- 17.1 min. Duration of analgesia with neostigmine group was 336.3 +/-
54.5 min and in normal saline group was 188.8 +/- 18.4 min. Conclusions:
Intrathecal neostigmine is associated with significantly prolonged sensory, motor
blockade, and effective postoperative analgesia.
PMID- 29962591
TI - Comparison of Palonosetron, Dexamethasone, and Palonosetron Plus Dexamethasone as
Prophylactic Antiemetic and Antipruritic Drug in Patients Receiving Intrathecal
Morphine for Lower Segment Cesarean Section.
AB - Background: Intrathecal morphine is commonly used for postcesarean analgesia. Its
use is frequently associated with opioid-induced nausea, vomiting, and pruritus.
Palonosetron (0.075 mg) combined with dexamethasone (8 mg) is postulated to have
an additive effect over each drug alone. The study, therefore, compared the
effect of intravenous (i.v.) palonosetron, dexamethasone, and palonosetron with
dexamethasone combination in preventing intrathecal morphine-induced
postoperative vomiting and pruritus in lower segment cesarean section (LSCS)
patients. Settings and Design: Randomized, prospective, double-blinded,
observational clinical study. Methods: Ninety pregnant women, American Society of
Anesthesiologists physical status class I undergoing LSCS were included in the
study. They were randomly assigned to three groups - Group P received 0.075 mg
palonosetron i.v., Group D received dexamethasone 8 mg i.v., and Group PD
received palonosetron 0.075 mg along with dexamethasone 4 mg i.v., just after
spinal anesthesia with bupivacaine 2.2 ml (12 mg) and 150 MUg morphine. The
incidence of pruritus, nausea, vomiting, and need for rescue drug were recorded
for 24 h. Statistical Analysis: Statistical analysis was performed using
Student's t-test for categorical variables and Chi-square test for noncategorical
variables. Results: The incidence of nausea, vomiting was significantly more in
Group D (40%) than Group P (27%) and Group PD (20%) in 24 h. The incidence of
pruritus was significantly more in Group D (6%) than Group P and PD (3%). The
need of rescue antiemetic was more in Group D (30%) than Group P (6%) and Group
PD (3%). No difference in three groups requiring rescue antipruritic drug.
Conclusion: Prevention of intrathecal morphine-induced vomiting and pruritus was
more effective with palonosetron alone or with dexamethasone combination than
dexamethasone alone. Combination of palonosetron and dexamethasone proved no
better than palonosetron alone.
PMID- 29962593
TI - A Comparative Study of Three Vasopressors for Maintenance of Blood Pressure
during Spinal Anesthesia in Lower Abdominal Surgeries.
AB - Introduction: Subarachnoid block, although being highly efficient with lesser
drug doses, often has limitation such as hypotension, continues to be a matter of
concern to the anesthetist. The present study was aimed to compare the use of
phenylephrine, ephedrine, and mephentermine bolus for maintenance of blood
pressure during spinal anesthesia in lower abdominal surgeries. Subjects and
Methods: In a randomized, prospective study, 90 adult patients of either sex who
developed hypotension during surgery under subarachnoid block were allocated into
three groups to receive bolus phenylephrine, ephedrine, and mephentermine. The
number of boluses and time taken to recover from hypotension was noted.
Occurrence of adverse effects in the perioperative and postoperative period was
also noted. Results: Results were analyzed by Student's paired t-test and Chi
square test. The ANOVA test was used to compare the group variances among the
study groups. P < 0.05 was considered statistically significant. Thirty-four
hypotensive events (average 1.03 events/patient) took place in mephentermine
group. In phenylephrine group, a total of 53 hypotensive events took place. On an
average, the group had a total of 1.61 hypotensive events per patient. No
hypotensive event took place in ephedrine group after the first bolus of drug
(average 1 event/patient). Mean heart rate in phenylephrine group was
significantly lower as compared to the other two groups (P < 0.001). Conclusion:
Mephentermine and ephedrine were similar in performance, offered a better
hypotensive control, and had lower recurring events as compared to phenylephrine.
PMID- 29962594
TI - Comparison of Effect of Airway Nebulization with Lignocaine 2% versus Ropivacaine
0.25% on Intubation and Extubation Response in Patients Undergoing Surgery under
General Anesthesia: A Randomized Double-Blind Clinical Trial.
AB - Context: Both intubation and extubation are associated with pressor response.
Aims: We aimed to evaluate if ropivacaine 0.25% nebulization would prevent
hemodynamic and cough responses to intubation and extubation and compared it with
lignocaine 2% and saline group. Settings and Design: This was a randomized double
blind clinical trial. Materials and Methods: A total of 75 patients classified as
the American Society of Anaesthesiologists physical status Classes I and II
belonging to 18-60 years were included in the randomized double-blind trial and
divided into three groups; Group 1: received 5 ml of normal saline, Group 2:
received 5 ml of 0.25% ropivacaine, Group 3: received 5 ml of 2% lignocaine
through nebulization before the induction. Patients were then administered
general anesthesia. Mean arterial pressure (MAP), heart rate (HR), and saturation
were recorded at baseline (T1), at intubation (T2), upon anesthetic withdrawal
(T3), upon eye opening (T4), upon extubation (T5), and 2 min after extubation
(T6). Cough response was recorded at emergence and extubation. Statistical
Analysis Used: Repeated measures analysis of variance were used to compare
hemodynamic variables and Chi-square test to compare the grades of cough between
the two groups. Results: The drug ropivacaine was found to be effective in
reducing the hemodynamic responses to both intubation and extubation when
compared to saline (P < 0.05). At extubation, though the mean values of HR and
MAP were lower in ropivacaine compared to lignocaine group, the difference did
not achieve statistical significance (P = 0.103 and 0.153 respectively). Only 40%
of patients who received ropivacaine had cough at extubation (P < 0.001).
Conclusion: Ropivacaine when used through nebulization preinduction effectively
reduced both intubation and extubation responses when compared to saline.
However, there was no significant difference between the ropivacaine and
lignocaine on extubation response.
PMID- 29962595
TI - Inter Scalene Block: Revisiting old technique.
AB - Background and Aims: The technique of percutaneous brachial plexus block has
persisted in many variations since first such block given by Hirsheli in 1911.[1]
Both supraclavicular and infraclavicular approaches have been described.
Consequent to perivascular technique (Winnie and Collins 1964), Winnie described
interscalene block (ISB) in 1970.[23] Winnie's was a single deposit block which
relied upon volume for its success. It is nearly 50 years that ISB has stood the
test of time and has evolved from single to multiple deposits Block. In mid-90s,
ultrasound guidance was first explored by anesthetists for regional anesthesia in
University of Vienna.[3] As ultrasound guidance is becoming popular and is
increasingly available to budding anesthetist, popularity of old technique has
started waning. In this study, old technique of ISB was revisited with a view to
assess its success rate with established drugs and examine if in light of
ultrasound guidance, this technique has become irrelevant for anesthetist today.
Methods: A retrospective study, a survey with high response rate, was done on
success rate of three variations of old technique of ISB in 100 patients. In
variation-1, thirty patients received two deposits of local anesthetic in
interscalene groove. In variation-2, thirty patients received four deposits of
local anesthetic in interscalene groove. In variation-3, forty patients received
six deposits of local anesthetic in interscalene groove along with infiltration
of both scalene muscles. In none of the variations, paraesthesia was sought or
peripheral nerve stimulator (PNS) or imaging gadget was used. Demographic data in
three variations were compared statistically using Chi-square and one-way ANOVA
test. Success rate among variations was analyzed by Fisher's exact test. Results:
In variation-1, 17 out of 30, in variation-2, 23 out of 30, and in variation-3,
37 out of 40 blocks were successful. Conclusion: Success of ISB given without PNS
or ultrasound guidance is directly proportional to the number of deposits of
local anesthetic made in interscalene groove.
PMID- 29962596
TI - Intermittent Transcutaneous Electrical Nerve Stimulation versus Transversus
Abdominis Plane Block for Postoperative Analgesia after Infraumbilical Surgeries.
AB - Background: Multimodal analgesia is currently recommended for effective
postoperative analgesia. Aim: The aim of this study is to compare the efficacy of
transversus abdominis plane (TAP) block with intermittent transcutaneous
electrical nerve stimulation (TENS) in postoperative patients after
infraumbilical surgeries under spinal anesthesia with respect to postoperative
analgesia, rescue analgesia, hemodynamic changes, block characteristics,
nausea/vomiting score, sedation score, adverse effects, and patient satisfaction.
Settings and Design: This was a prospective, observational study randomized
controlled trial. Methods: A total of 60 American Society of Anesthesiologists
physical status Classes I and II patients of 20-60 years scheduled for
infraumbilical surgeries were randomized by a computer-generated list into two
groups of 30 each, to receive either TAP Block (Group TAP: 15 ml of 0.25%
levobupivacaine on each side of abdomen) or TENS (Group TENS: TENS with frequency
of 50 Hz and intensity of electrical stimulation 9-12 mA, continued for 30 min
every 2 h till 24 h). The primary outcome was to compare the postoperative
analgesia as assessed using visual analog scale score. Secondary objectives were
to compare rescue analgesia, nausea/vomiting score, sedation score, the block
characteristics, adverse effects, hemodynamic changes, and patient satisfaction.
Statistical Analysis Used: Student's t-test, Chi-square test as applicable and
Statistical Package for Social Sciences (version 23.0, 2017, SPSS Inc., Chicago,
IL, USA) were used. Results: Time to the first analgesic requirement was 12.87 +/
4.72 h in Group TAP and 9.93 +/- 3.63 h in Group TENS (P < 0.008), the
difference between two groups was significant. Conclusion: TAP block is better
modality due to ease of application and prolonged analgesia.
PMID- 29962597
TI - Intraperitoneal Levobupivacaine Alone or with Dexmedetomidine for Postoperative
Analgesia after Laparoscopic Cholecystectomy.
AB - Background and Aims: Local anesthetic injection in the peritoneal cavity
decreases intensity of postoperative pain after laparoscopic surgeries. We
compared adding dexmedetomidine to intraperitoneal levobupivacaine in patients
undergoing laparoscopic cholecystectomy. Methods: A total of 105 patients were
included in this prospective, double-blinded, randomized study. Patients were
randomly divided into three equal sized (n = 35) study groups. Group C patients
received intraperitoneal 40 ml normal saline as controlled group. Group L was
given 40 ml 0.25% levobupivacaine. Group LD received 40 ml 0.25% levobupivacaine
+ dexmedetomidine 1 MUg/kg. The degree of postoperative pain was measured by
visual analog scale (VAS) score. The time of first analgesic demand was recorded
and also total dose of painkiller in the first 24 h and postoperative
complications were collected. SPSS version 16 was used for statistical analysis.
P < 0.05 was considered statistically significant. Results: Postoperative VAS at
different time intervals was significantly lower, time to the first demand of
painkiller (min) was longer (30.2 +/- 14.4, 45.9 +/- 20.1, and 56.5 +/- 13.2),
and total painkiller consumption (mg) was lower (203.5 +/- 42.9, 117.8 +/- 63.7,
and 46.3 +/- 41.3) in Group LD than Group L than Group C. Conclusion: Adding
dexmedetomidine to intraperitoneal levobupivacaine is superior to and gives
better results than levobupivacaine alone in patients undergoing laparoscopic
cholecystectomy.
PMID- 29962598
TI - Dexamethasone Compared to Dexmedetomidine as an Adjuvant to Local Anesthetic
Mixture in Peribulbar Block for Vitreoretinal Surgery. A Prospective Randomized
Study.
AB - Background: Dexamethasone or dexmedetomidine may improve the quality of
peribulbar block. Aim: The aim of this study is to compare the effects of adding
either dexamethasone or dexmedetomidine to peribulbar block on the efficacy,
intraocular pressure (IOP), time to first analgesic request, total analgesic
requirement, and side effects in patients undergoing vitreoretinal surgery.
Design: This was a clinical prospective randomized study. Patients and Methods:
One hundred and fifty adult patients scheduled for vitreoretinal surgery with
peribulbar block were randomized into three groups (50 patients each). Group I
received 3.5 ml of 0.5% bupivacaine and 3.5 ml of 2% lidocaine + 1 ml normal
Saline. 4 mg dexamethasone and 25 MUg dexmedetomidine in 1 ml were added to the
local anesthetic mixture in Groups II and III respectively. Onset and duration of
sensory and motor blocks, adequate time to start surgery, IOP, time to first
request of rescue analgesia, total analgesic consumption, and side effects were
recorded. The statistical software SPSS 16 was utilized for statistical analysis.
Results: Dexamethasone and dexmedetomidine groups showed significantly prolonged
duration of corneal anesthesia (234.07 +/- 1.37 and 233.54.1.97 min
respectively), prolonged lid and globe akinesia (194.27 +/- 1.63 and 194.73 +/-
2.35 min respectively) with prolonged time to first request of analgesia and less
consumption of rescue analgesia as compared to control group (P < 0.05) with non
significant differences between both groups (P > 0.05). The onset of corneal
anesthesia as well as lid and globe akinesia were enhanced in dexmedetomidine
group compared to the other two groups (P < 0.05). In addition, the measurement
of IOP was significantly less in the dexmedetomidine group after 10 min. All the
patients were hemodynamically stable with no side effects observed. Conclusion:
The addition of dexamethasone and dexmedetomidine to local anesthetic mixture in
peribulbar block for vitreoretinal surgeries provided safe and effective block
with prolonged duration and decreased requirements of postoperative analgesia
with better quality for dexmedetomidine group regarding the fast onset of the
block and reduced IOP.
PMID- 29962599
TI - Intrathecal Nalbuphine versus Ketamine with Hyperbaric Bupivacaine in Lower
Abdominal Surgeries.
AB - Background: Spinal anesthesia is an effective method of anesthesia with fewer
side effects. The main limitations include the shorter duration of action and
shorter postoperative analgesia when performed only with local anesthetics. Aim:
The aim of this study is to compare adjuvants nalbuphine and ketamine to
hyperbaric bupivacaine in spinal anesthesia with respect to the duration of
analgesia, sensory and motor onset, hemodynamic status, and side effects.
Settings and Design: This was a prospective, randomized, double-blind study.
Materials and Methods: After ethical committee's clearance and informed consent,
90 patients of the American Society of Anesthesiologists physical status I and II
were randomly allocated in three groups N, K, and B who received 3 ml hyperbaric
bupivacaine with 0.8 mg nalbuphine, 3 ml hyperbaric bupivacaine with 25 mg
ketamine (preservative free), and 3 ml hyperbaric bupivacaine with 0.5 ml normal
saline, respectively. Statistical Analysis: Data were analyzed using paired t
test. Results were analyzed and compared to previous studies. SPSS-22 version of
software was used, released 2013, IBM Corp., Armonk, NY, USA. Results: Mean
duration of analgesia in Group N, K, and B was 290 +/- 6.09, 220 +/- 5.03, and
154 +/- 6.04 min, respectively. Mean time of sensory onset in Group N, K, and B
was 2.08 +/- 0.34, 3.5 +/- 0.25, and 4.5 +/- 0.37 min, respectively. Time of
motor onset was 7.60 +/- 0.58, 7.79 +/- 0.37, and 7.82 +/- 0.53 min in Group N,
K, and B, respectively. Conclusion: Nalbuphine is an effective adjuvant in spinal
anesthesia with respect to sensory onset, duration of analgesia, and hemodynamic
stability.
PMID- 29962600
TI - Advantages of 1-1-12 Wash in Scheme during Induction with Low Flow Anesthesia
with and without Nitrous Oxide.
AB - Introduction: In the past, many wash-in schemes have been used with initially
high fresh gas flow (FGF) to achieve the necessary alveolar concentration of
inhalational agent in 10-15 min. This study was designed to show whether 1-1-12
wash-in scheme proposes an earlier achievement of induction or is there any
requirement of high FGF phase to know the time taken for induction with and
without nitrous oxide (N2O). Aims: The aim of the study was to find out the time
required for the alveolar concentration of desflurane to be from 1% to 6% with
and without N2O. Design: It was a potential randomized study which was conducted
on sixty patients admitted for elective surgery. Materials and Methods: Two
groups of thirty patients each were made and randomly assigned. Group N received
desflurane with N2O plus oxygen and Group A received desflurane with air plus
oxygen. Statistical Analysis: The observations were noted and evaluated
accordingly. Analysis was done using unpaired t-test. Results: Hemodynamic
parameters were almost similar in both the groups. In Group N, gradual FAD
(Alveolar Desflurane concentration, i.e., end-tidal desflurane) from 1% to 6% was
achieved at 0.5, 1, 1.5, 2, 3, and 4 min. In Group A, the same was achieved at
0.6, 1, 1.5, 2, 3, and 4 min (P > 0.05). No significant difference was found
between the recuperation time and score in both the groups. Rather complications
were more in Group N and statistically significant for nausea and vomiting.
Conclusion: Time taken to attain FAD from 1% to 6% was 4 min in both the groups.
It is concluded that the recitation of 1-1-12 wash-in scheme is autonomous on the
use of N2O and high FGF phase.
PMID- 29962601
TI - Intraperitoneal Instillation of Bupivacaine and Ropivacaine for Postoperative
Analgesia in Laparoscopic Cholecystectomy.
AB - Background: Intraperitoneal instillation of local anesthetics in laparoscopic
cholecystectomy (LC) has been used to reduce postoperative pain and to decrease
the need for postoperative analgesics. Aims: This study aimed to compare
intraperitoneal instillation of bupivacaine and ropivacaine for postoperative
analgesia in patients undergoing LC. Settings and Design: This was a prospective,
randomized, double-blind study. Materials and Methods: After obtaining ethical
committee's clearance and informed consent, sixty patients, aged 18-65 years, of
either gender, and American Society of Anesthesiologists physical status I to III
scheduled for LC were included and categorized into two groups (n = 30). Group A
patients received 20 mL of 0.5% bupivacaine intraperitoneally after
cholecystectomy and Group B patients received 20 mL of 0.5% ropivacaine
intraperitoneally after cholecystectomy. Statistical Analysis: The data were
analyzed using paired t-test. The results were analyzed and compared to previous
studies. SPSS software version 22 was used, released 2013 (IBM Corp., Armonk, NY,
USA). Results: Pulse rate, systolic blood pressure, and diastolic blood pressure
were comparatively lower in Group B than in Group A. The visual analog scale
(VAS) score was significantly lower in Group B. Rescue analgesia was given when
VAS was >6. Verbal rating scale score was significantly lower in Group B, showing
longer duration of analgesia in this group. Rescue analgesic requirement was also
less in Group B. Conclusion: The instillation of bupivacaine and ropivacaine
intraperitoneally was an effective method of postoperative pain relief in LC. It
provided good analgesia in immediate postoperative period with ropivacaine,
providing longer duration of analgesia.
PMID- 29962603
TI - Comparative Evaluation of Sevoflurane, Propofol, and Combination of Sevoflurane
and Propofol on Insertion Characteristics of Reusable Classic Laryngeal Mask
Airway.
AB - Background and Aim: Adequate depth of anaesthesia is needed for successful
placement LMA. under lighter plane of anaesthesia inadequate mouth
opening,coughing,body movements can lead to rejection of LMA and may be
associated with breath holding and bronchospasm. Use of propofol in doses which
allow adequqate jaw relaxation and prevent patient reaction to LMA commonly
results in hypotension and prolonged apnoea. Apart from minimal respiratory
irritant properties sevoflurane as compared to propofol has the advantage of
providing better hemodynamic stability and a smoother transition to the
maintainance phase without a period of apnea. However sevoflurane is associated
with delayed jaw relaxation and a longer time for the insertion of the LMA.Our
hypothesis is that induction of anaesthesia with the combination of sevoflurane
and small dose of propofol may optimize the insertion conditions of LMA and
decrease the side effects of individual drugs. Methods: 90 patients aged 18-65
yrs ASA physical status I and II undergoing elective procedures were randomly
allocated into 3 groups of 30 patients each. No patient had been given any
premedication. Patients in group P were induced with iv inj propofol 3 mg/kg.
Patients in group S an SP were induced with tidal volume breathing induction
technique using sevoflurane 8% along withN20: 02: 67:33 @ 6L/MIN In addition, in
group SP after loss of eye lash reflex patients were given IV propofol 1.5 mg/kg.
An independent observer assessed insertion characteristics. Results: our results
showed that induction of anesthesia using the combination of sevoflurane and
propofol resulted in the most frequent successful LMA insertion at first attempt
as compared with induction of anesthesia with either sevoflurane or propofol
alone.
PMID- 29962602
TI - A Comparative Study of Two Different Intravenous Bolus Doses of Phenylephrine
Used Prophylactically for Preventing Hypotension after Subarachnoid Block in
Cesarean Sections.
AB - Background and Aims: Hypotension occurs in most of the cases following
subarachnoid block in for cesarean sections. Studies comparing different bolus
doses of phenylephrine for preventing hypotension induced by subarachnoid block
in cesarean sections are sparse. Settings and Design: This study was conducted to
compare the efficacy of two different bolus doses of phenylephrine for preventing
subarachnoid block-induced hypotension in cesarean sections. Materials and
Methods: Sixty parturients undergoing cesarean section were allocated into two
groups. Group A (n = 30) received 150 mcg phenylephrine intravenously (IV) and
Group B (n = 30) received 200 mcg phenylephrine IV prophylactically immediately
after subarachnoid block. Then, for every 2 min, systolic blood pressure,
diastolic blood pressure, mean arterial pressure (MAP), and heart rate (HR) were
measured for 20 min, and APGAR scores were measured. Statistical Analysis: The
observations are expressed as mean +/- standard deviation and were compared using
unpaired t-test. The statistical significance of difference between groups was
based on P value. P < 0.05 was considered statistically significant. Results:
There was no difference in preventing hypotension in both the groups, the
incidence in Group A being 16.6% and Group B also 16.6%. However, the rise in
systolic pressure in Group B was higher than Group A in the first 2-6 min. The
incidence of bradycardia was higher in Group B (43.3%) than Group A (20%).
Conclusions: Both the doses of phenylephrine were equally efficient in prevention
of hypotension after subarachnoid block. Lower prophylactic bolus phenylephrine
150 mcg IV is better in the prevention of hypotension after subarachnoid block in
cesarean sections as the incidence of bradycardia is higher with phenylephrine
200 mcg.
PMID- 29962604
TI - Comparative Evaluation of Three Different Doses of Spinal Isobaric Ropivacaine in
Patients Undergoing Day Care Perineal Surgeries: A Randomized Double-blind Study.
AB - Background and objective: Ropivacaine owing to its propensity of causing motor
blockade of reduced duration, is preferred for ambulatory day care surgery.
Intrathecal ropivacaine has shown effective analgesia for lower limb surgery. Our
study plans to evaluate spinal ropivacaine in three different doses in patients
undergoing day care perineal surgery. Methodolgy: 90 ASA-I patients scheduled to
undergo day care perineal surgery were randomized to receive intrathecal
ropivacaine. Group I (n=30) received 15mg of intrathecal ropivacaine, Group II
(n=30) received 18.75 mg of intrathecal ropivacaine and Group III (n=30) received
22.5 mg of intrathecal ropivacaine. Onset of sensory block at T 10, peak sensory
block level, duration of sensory block, onset and duration of motor block and
relevant safety data were recorded. Result: Onset of analgesia was significantly
shorter in Group III (3.5 min ; P <0.0001). However, time taken for peak sensory
blockade was comparable in group II and III (12.76 and 11.93 mins). Duration of
analgesia was longer and statistically significant in Group III (201.6 mins: P
<0.0001) when compared to Group I and II. Onset of motor block was observed to be
shortest in Group III (6.7 mins) and duration of motor block was longest in Group
III (153.73 mins). These two parameters were statistically significant than Group
I and II (P <0.0001). Conclusion: Intrathecal ropivacaine in a dose of 18.75 and
22.5 mg were observed to be equally effective in providing satisfactory
analgesia. However, higher dose was associated with profound sensory and motor
block.
PMID- 29962605
TI - Minimum Effective dose of Dexamethasone in Combination with Midazolam as
Prophylaxis against Postoperative Nausea and Vomiting after Laparoscopic
Cholecystectomy.
AB - Background: Postoperative nausea and vomiting (PONV) affects 20% and 30% of
patients. As many as 60%-80% patients at high risk may be affected. Dexamethasone
(D) and midazolam (M) are well studied as antiemetic. Use of D can be associated
with certain undesirable side effects so minimum dose is preferred. M is a
routinely used premedicant. Hence, this study was designed with both D and M in
high risk patients for PONV to find minimum effective dose of D. Aims: To
determine the minimum dose of D that combined with M would provide effective
prophylaxis of PONV after laparoscopic cholecystectomy (LC) in patients at high
risk for PONV. Setting and Design: This is a prospective, randomized double-blind
trial. Materials and Methods: One hundred and fifty-five patients scheduled for
elective LC were randomized to 5 groups of 31 each. Group C was given normal
saline, and the rest were administered D 1 mg (group MD1), 2 mg (group MD2), 4 mg
(group MD4), or 8 mg (group MD8) in combination with 0.04 mg/kg M at induction.
The incidence of nausea, vomiting, severity of nausea, and the use of rescue
antiemetic and postoperative pain was analyzed. Statistical Analysis: Chi-square
test was used to compare incidence of study variables. Independent Student's t
test was used for continuous variables. Demographic data were compared using
ANOVA. P < 0.05 was considered statistically significant. Results: The incidence
of nausea was significantly lower in group MD4 (29%) and MD8 (6%) compared to
placebo group (71%) (P < 0.001) and of vomiting was significantly lower in groups
of MD2 (58%), MD4 (48%), and MD8 (6%) compared with placebo (90%) (P < 0.001) at
24 h. There was significant reduction in nausea, pain severity, and incidence of
use of rescue antiemetic in MD4 and MD8 groups with no discernable side effects
of the drugs. Conclusion: We conclude that 4 mg D with M and 2 mg D with M is
effective for prevention of nausea and vomiting, respectively, in patients at
high risk for PONV undergoing LC.
PMID- 29962606
TI - Comparison of Intrathecal Nalbuphine Hydrochloride and Clonidine Hydrochloride as
an Adjuvant to Hyperbaric Bupivacaine in Abdominal Hysterectomy.
AB - Background: Various adjuvants for prolongation of intraoperative and
postoperative analgesia have been clinically studied in the literature. Aim: This
study was done to evaluate and compare the effects of nalbuphine and clonidine as
an adjuvant to bupivacaine in spinal anesthesia. Methods: In this prospective,
randomized, placebo control, double-blind, and comparative study, a total of
ninety patients of American Society of Anesthesiologists physical status Classes
I and II undergoing abdominal hysterectomy under subarachnoid block were randomly
divided into three groups. In addition to 15 mg of 0.5% hyperbaric bupivacaine
administered, patients of groups BS, BN, and BC received 0.9% normal saline, 1.6
mg nalbuphine, and 30 MUg clonidine, respectively. The total volume of drugs
administered intrathecally was made up to 3.5 ml by addition of sterile isotonic
normal saline in all. The onset time and duration of sensory and motor block,
duration of analgesia, and total dose of postoperative analgesic requirement in
the first 24 h were compared among groups. Hemodynamic changes and side effects
were also recorded. Results: Addition of study adjuvants brought significantly
faster onset of sensory and motor block. Patients in clonidine group showed
significantly longer mean time two segment sensory block regression (P < 0.05)
lowest seen in control group. The regression time of motor block to modified
Bromage Grade I was significantly longer in clonidine group and comparable in the
other groups. Adjuvants have significantly increased the mean duration of
analgesia, highest in clonidine group (P < 0.05). Conclusion: Intrathecal
clonidine is associated with prolonged motor and sensory block, better
hemodynamic stability, and less postoperative analgesic requirement as compared
to nalbuphine.
PMID- 29962607
TI - Predictors of Postoperative Ventilation in Scoliosis Surgery: A Retrospective
Analysis.
AB - Background: Patients undergoing corrective surgery for scoliosis may require
postoperative ventilation for various reasons. Aim: The aim was to study the
correlation of preoperative (pulmonary function test [PFT], etiology, and Cobb's
angle) and intraoperative factors (type of surgery, number of spinal segments
involved, blood transfusion, and temperature at the end of surgery) on
postoperative ventilation following scoliosis surgery. Settings and Design:
patients' medical records of scoliosis surgery at a tertiary care center during
2010-2016 were retrospectively analyzed. Materials and Methods: We studied
retrospectively 108 scoliosis surgeries done in our institute during this period
by the same group of anesthetists using standardized anesthesia technique. We
analyzed preoperative (etiology, preoperative PFT, and Cobb's angle) and
intraoperative factors (type of surgery, number of spinal segments involved,
blood transfusion, and temperature) influencing postoperative ventilation.
Statistical Analysis: For all the continuous variables, the results are either
given in mean +/- standard deviation, and for categorical variables as a
percentage. To obtain the association of categorical variables, Chi-square test
was applied. Results: Patients with Cobb's angle above 76 degrees and spinal
segment involvement of 11 +/- 3 required postoperative ventilation. Forced
expiratory volume in 1 s (FEV1%) <38 and forced vital capacity (FVC%) <38.23 of
the predicted could not be extubated. Increased blood transfusion and hypothermia
were found to affect postoperative ventilation. Conclusion: Preoperative factors
such as etiology of scoliosis, Cobb's angle, spirometric values FEV1% and FVC% of
predicted and intraoperative factors like number of spinal segments involved,
affect postoperative ventilation following scoliosis surgery. Increased blood
transfusion and hypothermia are the preventable factors leading to ventilation.
PMID- 29962608
TI - A Comparative Study of Intrathecal Bupivacaine and Bupivacaine with Different
Doses of Clonidine in Lower Limb Surgeries.
AB - Background: Intrathecal clonidine is a very safe, nonopioid adjuvant to local
anesthetics to prolong the duration of analgesia without any major side effects.
Objective: The purpose of the present study was to evaluate the efficacy of
clonidine in two different doses as an adjuvant to bupivacaine intrathecally in
lower limb surgeries. Materials and Methods: A total of 75 adult patients
scheduled to undergo lower limb surgeries were randomly allocated into either of
three groups of 25 patients. Group I received 12.5 mg bupivacaine, Group II
patients received bupivacaine 12.5 mg with clonidine 15 MUg, and patients in
Group III received bupivacaine 12.5 mg with clonidine 30 MUg intrathecally. A
total volume of 3 ml was made in all groups using normal saline. The hemodynamic
parameters, onset, and duration of sensory block, highest dermatomal level of
sensory block, motor block onset, time to complete motor block recovery, and mean
time to request of the first analgesic were recorded. Side effects or any other
complications were noted. Results: The mean time of onset of sensory block and
motor block was less in clonidine groups. The mean duration of sensory block was
significantly prolonged in clonidine groups as compared to study group. The
duration of motor block (in minutes) was significantly prolonged in Group III
(171.60 +/- 38.20) as compared to Group I (113.20 +/- 35.79) and Group II (115.20
+/- 38.41). The time of analgesic request in Group I was 148.16 +/- 43.99 min,
190.60 +/- 38.08 in Group II, and 200.80 +/- 59.85 min in Group III. Conclusions:
The addition of intrathecal clonidine 15 MUg to small dose bupivacaine increased
the spread, duration of analgesia, and produced effective spinal anesthesia with
stable hemodynamics and did not prolong postoperative motor block.
PMID- 29962609
TI - Comparison of Intrapleural with Paravertebral Levobupivacaine Analgesia for
Thoracoscopic Sympathectomy: A Randomized Controlled Study.
AB - Background: Palmar hyperhidrosis is a benign disease of excessive sweating in the
palm that exceeds the physiological state. Thoracoscopic sympathectomy is an
effective surgical treatment for localized hyperhidrosis. Aims: The aim of this
study was to compare paravertebral block (PVB) with intrapleural analgesia in
thoracoscopic sympathectomy. Settings and Design: A total of 90 patients physical
status American Society of Anesthesiologists Classes I or II scheduled for
arthroscopic thoracoscopic sympathectomy were enrolled in this study. Subjects
and Methods: Patients were randomly allocated into three groups; in the
controlled (C) group, no regional block was performed. In the intrapleural (I)
group or paravertebral (P) group using a volume of 20 ml of levobupivacaine 0.5%.
The first request for analgesia postoperatively was our primary concern.
Secondary outcomes included pain scores, the cumulative consumption of fentanyl
during the 1st postoperative day, pulmonary functions, blood gases, and
complications. Statistical Analysis Used: Statistical analysis was done using
Statistical Package for Social Sciences (SPSS 19.0, Chicago, IL, USA). Results:
First request of analgesia in paravertebral group was statistically significantly
longer when compared with either control or intrapleural group. In addition,
total fentanyl dose was significantly higher in control group when compared with
the other groups. Groups I and P showed statistically significant less pain
scores, better pulmonary function, and blood gases when compared with control
group. Conclusion: We concluded that either intrapleural or paravertebral
analgesia compared with control group in thoracoscopic sympathectomy resulted in
later request of analgesia, improved pain control, reduced analgesic requirements
postoperatively, preservation of lung function and acid-base balance. The PVB,
compared to intrapleural, had an advantage of longer and effective analgesia.
PMID- 29962610
TI - The Sedative and Propofol-Sparing Effect of Dexmedetomidine and Midazolam as
Premedicants in Minor Gynecological Day Care Surgeries: A Randomized Placebo
Controlled Study.
AB - Background and Aims: Ambulatory surgery is continually evolving specialty in the
majority of surgical procedures. Dexmedetomidine and midazolam are newer
adjuvants for sedation and reducing the dose of anesthetic agents. The aim of
this study was to compare the sedative and propofol-sparing effect of
dexmedetomidine and midazolam in minor gynecological day care surgeries.
Observer's Assessment of Activity and Sedation, dose of additional propofol,
Aldrete and street fitness score were studied as primary outcomes. Hemodynamic
parameters and side effects were evaluated as secondary outcomes. Materials and
Methods: A prospective randomized placebo-controlled study was conducted on 150
American Society of Anesthesiologists ASA physical status Classes I and II
gynecological patients between 18 and 50 years and were allocated into three
groups of fifty each. Group A received intravenous (i.v.) dexmedetomidine 0.1
MUg/kg, Group B received i.v. midazolam 0.04 mg/kg, and Group C received normal
saline 10 min before induction. Results: Sedation score was statistically highly
significant between Group A and B (P < 0.001). Between Group A and C, it was
statistically significant (P < 0.05); however, score was nonsignificant between
Groups B and C (P > 0.05). During recovery at 120 min after surgery, score 5 was
achieved equally by all three groups which was found to be statistically
insignificant (P > 0.05). Mean dose of additional propofol used was less in Group
A (14 +/- 9.25) than B (25 +/- 5.40) and C (53 +/- 10.96). On intergroup
comparison between all three groups, it was found to be statistically highly
significant (P < 0.001). Comparison of bispectral index (BIS) values between
Groups A and C and Groups B and C were highly significant (P < 0.001). However,
it was statistically significant between Groups A and B (P < 0.05). Aldrete
scoring and street fitness scores were highly significant between Groups A and B,
B and C, and also between Groups A and C (P < 0.001). No significant hemodynamic
derangements and side effects were noted in any of three groups. Conclusion:
Dexmedetomidine had good sedation and better recovery characteristics than
midazolam. BIS monitoring was helpful in maintaining the depth of anesthesia.
PMID- 29962611
TI - Attenuation of Hemodynamic Responses to Endotracheal Extubation with Different
Doses of Diltiazem with Lignocaine: A Placebo-Controlled Study.
AB - Introduction: Endotracheal extubation causes transient hemodynamic stimulation
leading to increase in blood pressure and heart rate (HR) due to increase in
sympathoadrenergic activity caused by epipharyngeal and laryngopharyngeal
stimulation. Lignocaine, a sodium channel blocker, attenuates the hemodynamic
response to tracheal extubation by inhibiting sodium channels in the neuronal
cell membrane, decreasing the sensitivity of the heart muscles to electric
impulses. Diltiazem, a calcium channel blocker, attenuates hemodynamic response
by blocking voltage-sensitive L type channels and inhibiting calcium entry
mediated action potential in smooth and cardiac muscle. Aims and Objectives: The
aims and objectives of this are to study and to compare the efficacy of
combination of intravenous (i.v.) diltiazem 0.1 mg/kg and i.v. lidocaine 1.0
mg/kg, diltiazem 0.2 mg/kg and lidocaine 1.0 mg/kg, lignocaine 1.0 mg/kg with
normal saline given to attenuate exaggerated hemodynamic extubation responses and
airway reflexes during extubation. Materials and Methods: This study was
undertaken with 105 patients belonging to the age group 20-65 years with physical
status ASA Classes I and II of either sex. Group A received injection diltiazem
0.1 mg/kg and preservative-free lignocaine 1 mg/kg. Group B received injection
diltiazem 0.2 mg/kg and lignocaine 1 mg/kg. Group C received injection lignocaine
1 mg/kg with normal saline. In this study group, the drug dosage was fixed based
on the previous studies. Results: At postextubation, significant difference in
HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
pressure (MAP) were observed from 1 to 10 min between three groups. The
difference in HR, SBP, DBP, and MAP were statistically significant between Group
C in comparison with Group A and Group B from 1 min postextubation to 10 min.
Conclusion: Combined diltiazem and lidocaine are more effective prophylaxis than
lidocaine alone for attenuating the cardiovascular responses to tracheal
extubation.
PMID- 29962612
TI - Comparative Evaluation between Sevoflurane and Propofol for Endotracheal
Intubation without Muscle Relaxants in Pediatric Cleft Surgeries.
AB - Background and Objectives: Endotracheal intubation is the most important and
crucial step during administration of general anesthesia. It is more so in
pediatric patients with associated deformities of cleft lip, palate, and
alveolus. Propofol, an intravenous (i.v.) induction agent, has profound
depressant effect on airway reflexes with a quick and smoother induction.
Similarly, sevoflurane, an inhalational agent, has relatively pleasant smell, low
airway irritability, and more cardiostable properties. Hence, we sought to
compare effectiveness of propofol with sevoflurane in achieving good intubation
conditions without the use of muscle relaxants. Materials and Methods: In this
prospective randomized study, eighty children belonging to American Society of
Anesthesiologist physical status Class I and II, aged 1-10 years, scheduled for
cleft surgery were included. All participants were premedicated. Patients were
allotted to Group A and Group B randomly. Group A received propofol and Group B
received sevoflurane as induction agents. Tracheal intubation was attempted in
all patients at 150 s. Intubation conditions were assessed by using Steyn
modification of Helbo-Hansen intubating conditions score. Statistical analysis
was done using Student's t-test and Chi-square test with P < 0.05 regarded as
significant. Results: Group B patients receiving sevoflurane had significantly
more clinically acceptable intubation conditions than patients of Group A
receiving i.v. propofol (P = 0.001). Conclusion: We conclude that intubation
conditions using inhalational 8% sevoflurane are superior to i.v. propofol of 3
mg/kg for tracheal intubation without muscle relaxants in children undergoing
cleft surgeries.
PMID- 29962613
TI - Efficacy of Pectoral Nerve Block using Bupivacaine with or without Magnesium
Sulfate.
AB - Background: Worldwide, breast cancer is the main common cancer among females. In
the United States, it affects one in eight women during their lifespan. In breast
cancer surgery, chronic pain can be developed from poorly managed acute
postoperative pain. The aim of the study was to use a safe, easy, and less
complicated method of regional block for reducing the postoperative pain after
mastectomy, which will reduce the incidence of chronic postmastectomy pain.
Materials and Methods: Ninety adult female patients with American Society of
Anesthesiologists Physical Status I, II, and III were allocated randomly into
three groups: Group C had general anesthesia; Group B had ultrasound-guided
pectoral nerve block (PECS block) (28mL 0.25% bupivacaine+2mL normal saline) plus
general anesthesia; and Group M had ultrasound-guided PECS block (total 28 mL of
Bupivacaine 0.25%+2mL of magnesium sulfat 50%) plus general anesthesia. Results:
The intraoperative fentanyl (MUg) used was significantly lower in Group B (110.4
+/- 26.3) and Group M (108.7 +/- 14.1) than in Group C (214.3 +/- 20.1) and also
the same as regards the total postoperative pethidine (mg) in Group C (220 +/-
25.5), Group B (100.6 +/- 24.3), and Group M (52.3 +/- 12.3). The Group M was the
least group suffered from postoperative pain at all times of measurement.
Conclusion: The Group M was the least group suffered from postoperative pain at
all times of measurement.
PMID- 29962614
TI - Study Comparing Phenylephrine Bolus and Infusion for Maternal Hypotension and
Neonatal Outcome during Cesarean Section under Spinal Anesthesia.
AB - Background: Phenylephrine(PE) bolus and infusion have been compared for post
spinal hypotension and neonatal effects during cesarean section(CS) under spinal
anesthesia(SA). Aim: The primary aim of this study was to compare bolus doses of
50MUg of PE with a fixed infusion rate of 50 MUg/min of the same drug given
prophylactically. The secondary aim was to study the neonatal outcome and side
effects with the two regimes. Settings and Design: This
prospective,randomized,comparative study was conducted in the department of
Anesthesia in a tertiary care teaching hospital. Materials and Methods: This
study was conducted on 100 normotensive women undergoing CS under SA. The
patients were randomized into two groups of 50 each. Group A received bolus of 50
MUg PE after the systolic BP(SBP) fell by 20% from the baseline and Group B
received a prophylactic infusion of 50 MUg/min PE. The changes in heart rate
(HR), BP and side effects were compared till delivery. The neonatal APGAR scores
were compared at 1 and 5 minutes and an umbilical artery sample was sent for
blood gas analysis. Statistical Analysis: Categorical variables were shown in
number and percentage. Normally distributed continuous variables were presented
as mean +/- SD and compared using unpaired t-test. Non normally distributed
continuous variables were displayed as median and were compared using Mann
Whitney test. A P value of <0.05 was considered significant. Results: In group A,
the HR was higher than in group B throughout the monitoring period. (P < 0.001).
In group A, SBP trend showed a fall of more than 20% from the base line in 44
patients. The mean fall in SBP was -28.06 +/- 5.3 mmHg% in Group A while in group
B the mean fall in SBP was only -0.44 +/- 4.3mmHg%. Nausea and vomiting was less
in group B. There was no difference in APGAR or neonatal acidosis on ABG.
Conclusion: There was a tighter control of BP in the infusion group vs. the bolus
group while the neonatal outcome was similar in both the groups.
PMID- 29962615
TI - A Randomized Comparison of Pain Control and Functional Mobility between Proximal
and Distal Adductor Canal Blocks for Total Knee Replacement.
AB - Background: Adductor canal blocks (ACBs) have become a popular technique for
postoperative pain control in total knee arthroplasty patients. Proximal and
distal ACB have been compared previously, but important postoperative outcomes
have yet to be assessed. Aims: The primary objective of this study is to compare
postoperative analgesia between proximal and distal ACB. Secondary outcomes
include functional mobility, length of stay (LOS), and adverse events. Settings
and Design: This study was a single-center, assessor-blinded, randomized trial.
Subjects and Methods: Fifty-seven patients were randomly assigned to receive a
proximal (n = 28) or distal (n = 29) ACB. A 20 mL bolus of 5 mg/mL ropivacaine
was injected at the respective location followed by 2.0 mg/mL ropivacaine
infusion for 24 h. Statistical Analysis: The primary outcome was intra- and
postoperative 24-h opioid consumption in intravenous (IV) morphine equivalents.
Secondary outcomes include percentage change in timed "Up and Go" (TUG) times,
LOS, and average postoperative pain scores. Continuous variables were compared
using Student's t-test. Results: The mean (+/-standard deviation) 24-h intra-and
postoperative opioid consumption showed no difference between the proximal and
distal groups (39.72 +/- 23.6 and 41.28 +/- 19.6 mg IV morphine equivalents,
respectively, P = 0.793). There was also no significant difference in the median
[minimum, maximum] percentage change in TUG times relative to preoperative
performance comparing proximal and distal ACB (334.0 [131, 1084] %-change and
458.5 [169, 1696] %-change, respectively, P = 0.130). In addition, there were no
differences in postoperative pain scores or LOS. Conclusions: ACB performed at
either proximal or distal locations shows no difference in postoperative pain
measured by opioid consumption or pain scores. Better TUG performance seen in the
proximal group was not statistically significant but might represent a clinically
important difference in functional mobility.
PMID- 29962616
TI - Comparison of Morphine and Clonidine as Adjuvants in Paravertebral Block.
AB - Background: General anesthesia (GA) has been considered as the gold standard for
breast cancer surgery. The problem of postoperative pain as well as the high
incidence of nausea and vomiting has led to the search for a better modality for
pain management with fewer side effects. In the last few years, paravertebral
block (PVB) has gained immense popularity either in combination with GA or by
itself for the anesthetic management of patients undergoing breast surgery.
Context: Paravertebral block in breast surgery. Aims: This study aims to evaluate
the efficacy and duration of postoperative analgesia provided by ultrasound (USG)
guided PVB with bupivacaine and morphine versus bupivacaine and clonidine in
patients undergoing modified radical mastectomy (MRM). Subject and Methods: In
the study, 70 patients who were scheduled for MRM were enrolled and randomly
divided into Group M (n = 35) and Group C (n = 35). Both groups received USG
guided PVB at T2-T3 after administering GA. Group M received 2 mg/kg 0.5%
bupivacaine with 0.05 mg/kg morphine and Group C received 2 mg/kg 0.5%
bupivacaine with 1 MUg/kg clonidine in the block. Postoperatively, pain intensity
was recorded using the visual analog scale (VAS) (0-10 scale) at 1, 2, 6, 18, and
24 h duration when patients were resting and during a standardized movement.
Modified Post Anaesthesia Discharge Scoring System was assessed at 1, 2, 6, 18
and 24 h after surgery. Results: In this study conducted on 70 patients, VAS
scores (both at rest and on movement) were found comparable at postoperative 1,
2, 6, 18, and 24 h (P > 0.05). There was no statistical difference in comparing
postanesthesia discharging scoring in both the groups. No incidence of
postoperative nausea and vomiting was seen in any group. Conclusions: Morphine
and clonidine in PVB are equally effective, and there is no superiority of one
agent over the other. Hence, both drugs may be used with equal efficacy as
adjuvants to bupivacaine in PVB for providing postoperative analgesia.
PMID- 29962617
TI - Comparison of Ketamine with Midazolam versus Ketamine with Fentanyl for Pediatric
Extracorporeal Shock Wave Lithotripsy Procedure: A Randomized Controlled Study.
AB - Objectives: To compare the effects of ketamine-fentanyl (KF) and ketamine
midazolam (KM) combinations on hemodynamic parameters, recovery properties, pain,
and side effects in pediatric patients undergoing extracorporeal shock wave
lithotripsy (ESWL) procedure. Methodology: In this double-blinded, randomized
trial, 60 pediatric patients aged between 1 and 13 years with American Society of
Anesthesiologists physical status Classes I and II, who scheduled for ESWL
procedure, were included in the study. Patients were randomly divided into two
groups: Group KM received 0.1 mg/kg of midazolam +1-1.5 mg/kg of ketamine and
Group KF received 1 MUg/kg of fentanyl +1-1.5 mg/kg of ketamine intravenously.
Results: There were similar demographic properties, recovery, and discharge times
between groups. No statistically significant difference was found in peripheral
oxygen saturation, mean and diastolic blood pressure, Ramsey sedation scores,
modified Aldrete recovery scores, side effects, and recovery times (Group KM,
16.067 +/- 1.2 min; Group KF, 19.46 +/- 0.86 min) between groups (P > 0.05).
Conclusion: KF combination offers better hemodynamic properties, less side
effects with lower visual analog scores, and face, legs, activity, cry, and
consolability scores than KM in the pediatric ESWL procedure.
PMID- 29962618
TI - Comparison of Two Doses of Dexmedetomidine for Supraclavicular Brachial Plexus
Block: A Randomized Controlled Trial.
AB - Background: Dexmedetomidine is commonly used as an additive in supraclavicular
brachial plexus block (SBPB). Due to its adverse effects such as bradycardia and
hypotension, finding the appropriate dose of dexmedetomidine is the question.
Aims: We aimed to compare two commonly used doses of dexmedetomidine (1 MUg/kg
and 2 MUg/kg) added to levobupivacaine in ultrasound-guided SBPB in terms of its
effect on duration of analgesia, hemodynamics, and associated adverse effects.
Settings and Design: This randomized, double-blinded prospective study was
conducted over a period of 1.5 years in our tertiary care hospital. Materials and
Methods: Clearance from the Institutional Ethical Committee and Clinical Trial
Registry of India was taken. Ninety patients' physical status American Society of
Anesthesiologists Classes I and II undergoing upper limb surgeries under SBPB
were included in this study. Patients in Group I received 1 MUg/kg
dexmedetomidine, whereas patients in Group II received 2 MUg/kg dexmedetomidine
added to 20 cc levobupivacaine. The primary outcome measure was the duration of
analgesia after administering the block. Secondary outcomes included effect on
hemodynamics, duration of blockade, and adverse effects. Statistical Analysis:
Statistical analysis was carried out using Stata Version 10. Unpaired t-test and
Chi-square test were used. Results: The duration of analgesia and sensory and
motor blockade were similar in both the groups. The heart rate (HR) and mean
arterial pressure were statistically lower in Group II. The incidence of
bradycardia and hypotension was more in Group II. Conclusions: Increasing the
dose of dexmedetomidine does not prolong the duration of analgesia, but it is
associated with lower HR and blood pressure. Incidence of hypotension and
bradycardia is also more. Hence, a lower dose of 1 MUg/kg dexmedetomidine added
to 0.5% levobupivacaine is a good balance between safety and efficacy.
PMID- 29962619
TI - Dexmedetomidine and Fentanyl as an Adjunct to Bupivacaine 0.5% in Supraclavicular
Nerve Block: A Randomized Controlled Study.
AB - Background: Brachial plexus block is gaining popularity day by day for upper limb
surgery. The supraclavicular brachial plexus block may be used for surgical
anesthesia alone or in conjunction with general anesthesia. Aims: We intended to
compare the effect of dexmedetomidine and fentanyl as adjuvant to bupivacaine on
onset and duration of block and postoperative analgesia during ultrasonic guided
supraclavicular nerve block for upper limb surgeries. Settings and Design: This
study design was a prospective randomized controlled double-blinded clinical
study. Patients and Methods: Sixty patients with American Society of
Anesthesiologists physical status Classes I and II, aged 18-50 years, scheduled
for upper limb surgery were randomly divided into three study groups each group
contains 20 patients: C Group: receive 0.5 mL/kg up to a maximum of 40 mL volume.
The dose of bupivacaine was 1.5 mg/kg. D Group: Bupivacaine as control group + 1
mg/kg dexmedetomidine. F Group: Bupivacaine as control group + 1 mg/kg fentanyl.
Patients were observed for onset and duration of sensory and motor blockade,
duration of analgesia, postoperative pain, and adverse effects. Statistical
Analysis Used: One-way ANOVA test and Chi-square test were used. Results: The
onset time of sensory and motor blockade was shortened. and the duration of the
block was significantly prolonged in the D Group (P < 0.001) and F Group (P <
0.001). The duration of postoperative analgesia was also longer in the D Group
13.5 h compared with the F Group 8.3 h and C Group 7.5 h. Hypotension and
bradycardia were recorded in 2 patients in D Group, and nausea and vomiting were
recorded in F Group. Conclusions: Addition of dexmedetomidine was better in
prolongation of the duration of supraclavicular brachial plexus block and
improvement of postoperative analgesia than fentanyl and bupivacaine alone
without significant adverse effects in patients undergoing upper limb surgeries.
PMID- 29962620
TI - Would "Suction above Cuff" be a Better Option than the "Standard" Endotracheal
Tube for the Prevention of Ventilator-Associated Pneumonia: A Randomized Study in
Postoperative Neurological Patients.
AB - Context: Ventilator associated pneumonia is one the most common nosocomial
infection encountered in the ICU patients. Despite of the implementation of the
VAP prevention bundle, the incidence remains high. This can be attributed to the
peritubal leak and the aspiration of the oropharyngeal secretions. The secretions
further forms a nidus for the growth of organisms in the lower respiratory tract.
In this study, a specialised tube, named 'suction above cuff endotracheal tube'
is used, which has an additional suction port opening above the cuff. This is to
facilitate timely aspiration of the secretion which pent-up above the cuff and
gradually trickles down the trachea resulting in pneumonia. Aim: to compare the
incidence of VAP with standard endotracheal tube (SETT) and suction above cuff
endotracheal tube (SACETT) in neurological post-operative patients and its impact
on clinical outcome. Settings and Design: 60 patients of post-operative
neurological cases aged >= 18 years and requiring intubation and/or ventilation
and anticipated to remain on ETT for >=48 h were randomized to receive either
SETT or SACETT. Results: In this study involving neurological population, there
was no significant difference in incidence of clinical and microbiological VAP
between SETT and SACETT group, when other strategies for VAP prevention were
similar. Other outcomes were similar with use of either tube for intubation.
PMID- 29962621
TI - Effect of Cuff Pressures on Postoperative Sore Throat in Gynecologic Laparoscopic
Surgery: An Observational Study.
AB - Context: Postoperative sore throat (POST) is a very common complaint following
tracheal intubation. Although it resolves spontaneously, efforts must be taken to
reduce it. Aims: This study aims to compare the effect of cuff inflation using
manometer versus conventional technique on the incidence of POST. Secondary
objectives were to assess the incidence postoperative hoarseness and cough.
Settings and Design: A total of 120 patients were included in this prospective
observational comparative study. Subjects and Methods: After approval from the
hospital ethics committee, consenting American Society of Anesthesiologists
physical status Class I and II patients, scheduled for gynecologic laparoscopic
surgery under general anesthesia, were included. They were randomly allocated by
closed envelope technique to either Group A where the cuff pressure was adjusted
to 25 cmH2O using a manometer or Group B where cuff inflation was guided
clinically. Patients were monitored for sore throat, hoarseness of voice, and
cough postoperatively. Statistical Analysis Used: To calculate the incidence of
sore throat, hoarseness, and cough, descriptive statistics were applied. For
checking association of sore throat and cuff pressure, Chi-square test and for
comparing numerical values independent sample t-test were applied. Results: The
incidence of POST was significantly less in Group A than in B (P < 0.001) up to
24 h. Incidence of hoarseness was less in Group A and incidence of cough was
higher in Group B, but these differences were not statistically significant.
Conclusion: Cuff inflation guided by manometer significantly reduces the
incidence of POST.
PMID- 29962622
TI - The Comparison of the Efficacy and Safety of Midazolam, Ketamine, and Midazolam
Combined with Ketamine Administered Nasally for Premedication in Children.
AB - Background: In this prospective, randomized study, we evaluated the intranasal
administration of Midazolam ketamine combination, midazolam, and ketamine in
premedication for children. Material and Methods: We studied 60 American Society
of Anesthesiology physical status Classes I and II children aged between 1 and 10
years undergoing ear nose throat operations. All cases were premedicated 15 min
before operation with intranasal administration of 0.2 mg/kg midazolam in Group
M, 5 mg/kg Ketamine in Group K, and 0.1 mg/kg Midazolam + 3 mg/kg ketamine in
Group MK. Patients were evaluated for sedation, anxiety scores, respiratory, and
hemodynamic effects before premedication, 5 min interval between induction and
postoperative period. Results: There was no difference with respect to age, sex,
weight, the duration of the operation, and for mask tolerance. Sedation scores
were significantly higher in Group MK. There was no statistically difference
between the groups for heart rate, oxygen saturation, and respiratory rate.
Conclusion: We concluded that intranasal MK combination provides sufficient
sedation, comfortable anesthesia induction with postoperative recovery for
pediatric premedication.
PMID- 29962624
TI - Epidural Analgesia during Labor: Attitudes among Expectant Mothers and Their Care
Providers.
AB - Introduction: Varying levels of knowledge and attitudes among parturients and
physicians toward epidural analgesia result in its low utilization. We aimed to
assess the knowledge, attitude, and practice of parturients, obstetricians, and
anesthesiologists regarding epidural labor analgesia. Methodology: We surveyed
obstetricians, anesthesiologists, and parturients availing care and later
delivered at our hospital from July 1, 2017, to December 31, 2017. Knowledge,
attitude, and practice regarding epidural analgesia were collected using a semi
structured predesigned questionnaire. Data were described as frequencies and
analyzed for association between parity and various beliefs and attitudes using
Chi-square or Fisher's exact test. Results: About 33% of the parturients knew
that delivery is possible without labor pains, but only 18% were satisfied with
the procedure. Timely epidural anesthesia could not be availed by 83% of the
parturients due to unavailability of service. Among the obstetricians, 64%
preferred epidural analgesia and thought that epidural analgesia prolongs the
duration of labor, and 55% thought that it would increase the incidence of lower
uterine segment cesarean section (LUSCS). In our survey, 48% of all
anesthesiologists thought that epidural analgesia would lead to an increase in
the incidence of instrumental delivery, 52% required intravenous analgesics with
epidural, and 63% thought that it would not increase the incidence of LUSCS. Fear
of labor and delivery pain, knowledge status, unwillingness and demand for
epidural analgesia, satisfaction level, and reasons for not undergoing the
procedure were significantly associated with the gravid status. Conclusion: Wide
gap between desire for labor analgesia and its availability exists. A
collaborative approach between anesthesiologists and obstetricians is required to
disseminate correct information regarding epidural analgesia.
PMID- 29962623
TI - Intrathecal Tramadol for Prevention of Postanesthesia Shivering after
Subarachnoid Block: A Prospective Randomized Placebo-Controlled Comparison of Two
Different Doses (10 and 20 mg).
AB - Background: Shivering is a common and distressing complication following
subarachnoid block (SAB). Literature comparing the antishivering efficacy of
different doses of intrathecal (IT) tramadol is lacking. Aims: This prospective
randomized controlled study was undertaken to evaluate and compare the
antishivering efficacy of IT tramadol 10 and 20 mg. Methods: Ninety adult
patients undergoing lower limb orthopedic surgeries under SAB were randomized
into three groups (n = 30) to receive IL 0.5% hyperbaric bupivacaine 3 ml with
tramadol 0 mg (Group C), 10 mg (Group T10), or 20 mg (Group T20) in normal
saline. Shivering was assessed using a 5-point intensity scoring system
intraoperatively and up to 4-h postoperatively. The onset and duration of sensory
and motor block, duration of analgesia, and adverse effects were assessed.
Statistical Analysis Used: Analysis of variance and Pearson Chi-square test were
used for statistical analysis. Results: The incidence and intensity of shivering
were significantly reduced in Group T10 versus C (incidence, P = 0.007;
intensity, P = 0.002) and T20 versus C (incidence, P < 0.001; intensity, P <
0.001) but comparable among groups T10 and T20 (incidence, P = 0.133; intensity,
P = 0.142). There was a significant dose-dependent prolongation of duration of
sensory block (121, 137, and 150.5 min; P = 0.001), motor block (242.83, 298.5,
and 344 min; P < 0.001), and analgesia (289.17, 357, and 404.67 min; P < 0.001)
with escalating doses of IT tramadol, respectively. All the groups were
comparable with respect to hemodynamic variables, core temperature, and adverse
effects. Conclusion: The addition of tramadol 10 or 20 mg IT to 0.5% hyperbaric
bupivacaine for SAB is associated with significant reduction in the incidence and
intensity of postanesthesia shivering and prolongation of the duration of
postoperative analgesia. Tramadol 20 mg IT compared to 10 mg IT significantly
prolonged the duration of postoperative analgesia but failed to demonstrate any
significant attenuation of postanesthesia shivering.
PMID- 29962625
TI - Comparison of Nasopharyngeal Temperature Measured at Fossa of Rosenmuller and
Blindly Inserted Temperature Probe with Esophageal Temperature: A Cross-Sectional
Study.
AB - Introduction: Monitoring body temperature and maintaining normothermia are now
essentially the standard-of-care during anesthesia. This study was designed to
compare the temperature measured by nasopharyngeal temperature probes inserted by
landmark method and fiberscope-guided method with esophageal temperature. We
hypothesized that placing the temperature probe at the level of fossa of
Rosenmuller will reflect core temperature as it is in close relationship to the
brain. Subjects and Methods: Sixty-five patients aged 18-60 years were enrolled
in this cross-sectional study. Two methods were used in our study to place the
temperature probes. In landmark-based method, we inserted temperature probe
through nostril for a depth equal to philtrum-tragus distance. In fiberscope
guided method, the temperature probe was inserted into nostril and its tip was
positioned at fossa of Rosenmuller under fiberscope guidance. Results: The
nasopharyngeal temperatures were recorded at seven time intervals along with
esophageal temperature. Mean temperatures were calculated at three different
sites. The degree of agreement between two methods at seven time intervals was
also calculated. Both methods had good correlation with esophageal temperature.
Depth of insertion of temperature probes was documented. There was difference in
depth of insertion of temperature probe of around 4.26 cm between two methods,
probe length from philtrum to tragus (D1) being longer than distance from fossa
of Rosenmuller to nares (D2). Conclusions: Nasopharyngeal temperature measured at
fossa of Rosenmuller with probe inserted by fiberscope-guided method and that
measured by landmark-based method with probe inserted according to philtrum
tragus distance shows good correlation with esophageal temperature.
PMID- 29962626
TI - Minimum Alveolar Concentration of Desflurane for Maintaining BIS Below 50 in
Children and Effect of Caudal Analgesia on it.
AB - Context: Neuraxial techniques have sedative properties secondary to decreased
inputs from sensory and motor afferents. We hypothesized that caudal analgesia
decreases the requirement of desflurane as measured by bispectral index (BIS).
Aims: This study aims to determine the minimum alveolar concentration (MAC) of
desflurane for maintaining BIS below 50 (MACBIS50) in children undergoing
infraumbilical surgeries with laryngeal mask airway (LMA) and study the effect of
caudal analgesia on the same. Settings and Design: This is prospective and
observational study. Subjects and Methods: Thirty-nine American Society of
Anesthesiologists physical status Classes I and II children in between 1 and 8
years of age undergoing elective infraumbilical surgery under general anesthesia
were allocated randomly into two groups (Group C and Group D) after induction
with sevoflurane and LMA insertion. In Group C, caudal block was performed with
0.75 mL/kg of 0.25% bupivacaine and BIS values were recorded after 10 min for 1
min at 10 s intervals. In Group D, BIS was recorded for desflurane for 1 min at
10 s intervals followed by a caudal block with the same dose. Statistical
Analysis Used: Dixon up-down method with a step size of 0.5%, and probit analysis
were used for analysis. Results: A total of 39 patients were enrolled. MAC of
desflurane for maintaining MACBIS50 was 5.57 (95% confidence interval [CI] 5.22
5.95) in Group D and 4.31 (95% CI 3.12-5.08) in Group C. The use of caudal
anesthesia lowered the MAC of desflurane for maintaining MACBIS50 in children by
22.36% (P < 0.001). Conclusions: The use of caudal analgesia significantly
reduced MAC of desflurane for maintaining MACBIS50 in children undergoing
infraumbilical surgeries using LMA.
PMID- 29962627
TI - Comparison of Goal-Directed Hemodynamic Optimization Using Pulmonary Artery
Catheter and Autocalibrated Arterial Pressure Waveform Analysis Vigileo-FloTracTM
System in On-Pump Coronary Artery Bypass Graft Surgery: A Randomized Controlled
Studya.
AB - Background: It is a challenge for anesthesiologists to balance between
administering intravenous fluid, vasoactive agents, and inotropic drugs to
maintain appropriate cardiac output. Aim: The aim of this study was to evaluate
the effect of treatment algorithm guided either by pulmonary artery catheter
(PAC) or by the fourth generation FloTrac/Vigileo system combined with monitoring
of oxygen transport on hemodynamic management and outcome after coronary artery
bypass graft surgery (CABG). Settings and Design: This study design was a
prospective randomized controlled clinical study. Patients and Methods: Sixty
patients aged 45-65 years, scheduled for CABG surgery for two or more grafts with
cardiopulmonary bypass, were randomized into two groups 30 patients in each; (1)
(Group P) patients in which PAC was inserted into internal jugular vein and
connected to monitor. (2) (Group F) Patients in which arterial pressure catheter
was inserted in radial artery and connected to the FloTrac sensor and Vigileo
monitor. Statistical Analysis Used: Student's t-test or Mann-Whitney U-test and
Chi-square or Fisher's exact tests were used. Results: Central venous pressure
rose at the end of surgery in both groups and postoperatively declined
transiently. Although the volume of crystalloids administered during surgery did
not differ significantly between the groups, Group F received 24% more
crystalloids and 3-fold more colloids postoperatively. Duration of postoperative
respiratory support increased by 36% in Group P (P = 0.04). Conclusions: Goal
directed therapy based on pulse pressure analysis and oxygen transport increases
the volume of fluid therapy, improves hemodynamics, and reduces the duration of
respiratory support after CABG surgery.
PMID- 29962628
TI - Prevention of Emergence Delirium in Children - A Randomized Study Comparing Two
Different Timings of Administration of Midazolam.
AB - Background: Emergence delirium (ED) is a distressing side effect of sevoflurane
anesthesia in children. Midazolam is a widely studied drug for the prevention of
ED with conflicting results. Aim Settings and Design: We designed this
prospective randomized double-blind study to compare the effect of 0.03 mg/kg
midazolam administered at induction and the same dose administered 10 min before
the end of surgery in the prevention of ED in children undergoing sevoflurane
anesthesia and also the effect on the time to recovery in both groups. Materials
and Methods: Eighty children between 2 and 8 years belonging to patient physical
status American Society of Anesthesiologist Classes 1 and 2 undergoing infra
umbilical surgeries under general anesthesia were randomly allocated to receive
0.03 mg/kg midazolam at induction (Group A) and 10 min before the end of surgery
(Group B). Caudal block was administered for analgesia after induction. The
primary outcome, the incidence of ED was evaluated using the Paediatric
Anaesthesia Emergence Delirium Scale from the time of extubation till 30 min
postsurgery. The secondary outcome measured was the time to recovery (time from
discontinuation of sevoflurane to the time of extubation) and the results were
statistically analyzed. Results: The incidence of ED was comparable between the
groups (30%, 10%, 5%, and 2.5% at 5, 10, 15, and 20 min, respectively in Group A
and 25%, 10%, 5%, and 2.5% of children at 5, 10, 15, and 20 min, respectively in
Group B). Recovery was significantly prolonged in Group B (42.5% of patients in
Group A recovered within 6 min of discontinuation of sevoflurane in Group A
compared to only 20% of patients in Group B). Conclusion: There is no difference
in the reduction of incidence of ED following sevoflurane anesthesia when
midazolam is administered at induction or the end of surgery. However, the time
to recovery was longer when the drug was administered at the end of the surgery.
PMID- 29962630
TI - Postoperative Analgesic Efficacy of Intrathecal Fentanyl Compared to Nalbuphine
with Bupivacaine in Spinal Anesthesia for Lower Abdominal Surgeries.
AB - Context: Subarachnoid block or spinal anesthesia is a commonly used technique for
lower abdominal and lower limb surgeries. Bupivacaine is the commonly used cost
effective drug which gives satisfactory analgesia for 90-120 min. Additives such
as opioids and alpha2 agonists extend the analgesia in the postoperative period.
In this study, we compared the effects of nalbuphine with fentanyl. Aims: The aim
of this study is to compare the effects of intrathecal nalbuphine and fentanyl as
adjuvants to hyperbaric bupivacaine in regard to time of onset of sensory
blockade, duration of sensory blockade, two-segment sensory regression time,
duration of effective postoperative analgesia, and incidence of side effects.
Settings and Design: This was a prospective, randomized double-blind study.
Subjects and Methods: After ethical committee permission and patient consent, 124
patients aged 18-55 years with American Society of Anesthesiologists physical
status I and II were randomly divided into two groups - Group N: hyperbaric
bupivacaine with nalbuphine (300 MUg); Group C: hyperbaric bupivacaine with
fentanyl (25 MUg). Results: Duration of onset of sensory blockade was 3.9 +/-
0.35 min in Group C and 3.1 +/- 0.18 min in Group F. Two-segment sensory
regression time was prolonged in Group C (193.16 +/- 39.55) compared to Group F
(167.41 +/- 30.17 min). Conclusions: Intrathecal nalbuphine at a dose of 300 MUg
in 3 ml 0.5% heavy bupivacaine in patients undergoing elective lower abdominal
surgeries showed delay in onset time for sensory blockade and produced prolonged
postoperative analgesia, prolonged sensory blockade, and minimal bradycardia
which could be easily managed.
PMID- 29962629
TI - A Clinical Comparative Study of Fascia Iliaca Compartment Block with Bupivacaine
and Bupivacaine with Dexmedetomidine for Positioning and Duration of
Postoperative Analgesia in Fracture Femur under Spinal Anesthesia.
AB - Context: Positioning fracture femur cases for sub arachnoid block (SAB) is
challenging. Fascia iliaca compartment block (FICB) is low skilled, helps
positioning, and provides analgesia. Dexmedetomidine as an adjuvant prolongs
analgesia. Aims: The aims were to study and compare FICB with bupivacaine and
bupivacaine with dexmedetomidine in fracture femur cases with regard to
positioning during SAB, duration of analgesia in terms of Visual Analog Scale
(VAS), Numerical Rating Scale (NRS), and Patient Satisfaction Score, and assess
side effects. Settings and Design: This was a randomized, double-blind,
prospective study. Subjects and Methods: Sixty fracture femur patients were
divided into two groups as follows: Group A: FICB with injection bupivacaine
0.25% 38 cubic centimeter (cc) + dexmedetomidine 0.5 MUg/kg in 2 cc normal saline
(NS) and Group B: FICB with injection bupivacaine 0.25% 38 cc + 2 cc NS.
Statistical Analysis Used: Data were analyzed using SPSS 22.0 software.
Categorical data were processed by frequencies and proportions, whereas
continuous data were processed by mean standard deviation. Chi-square test and
independent t-test were used as tests of significance, considering P < 0.05 as
statistically significant. Results: In Group A, mean VAS score at 5 min (min) was
3.7 +/- 0.9 and in Group B it was 4.3 +/- 0.7. Similarly, at 15 min, mean VAS
score in Group A was 0.4 +/- 0.6 and in Group B it was 1.9 +/- 0.9. VAS score was
significantly high in Group B at 5, 10, and 15 min. Mean time to rescue analgesia
in Group A was 838.3 +/- 82.7 min and in Group B it was 461.5 +/- 36.6 min, which
was significant. Conclusion: FICB ensures patient comfort during positioning for
SAB and provides postoperative analgesia. Dexmedetomidine significantly prolongs
postoperative analgesia.
PMID- 29962631
TI - A Comparative Study of Dexmedetomidine and Clonidine as an Adjuvant to
Intrathecal Bupivacaine in Lower Abdominal Surgeries.
AB - Context: Spinal block is the first choice for lower abdominal surgeries.
Bupivacaine is the most common local anesthetic used but has a shorter duration
of action. Many adjuvants have been used to improve the quality of analgesia till
postoperative period. In this study, we used alpha2-agonists. Aims: The aim of
this study is to compare the effects of intrathecal dexmedetomidine and clonidine
as adjuvants to hyperbaric bupivacaine with respect to onset and duration of
sensory and motor blockade duration of analgesia and incidence of side effects.
Settings and Design: This was a prospective randomized double-blind study.
Subjects and Methods: One hundred and fifty patients of physical status American
Society of Anesthesiologists Classes I and II were randomly divided into Groups
B, C, and D each administered with bupivacaine with normal saline, clonidine, and
dexmedetomidine, respectively. Statistical Analysis Used: Data were entered into
Microsoft excel data sheet. Analysis software used in this study was SPSS 22
version IBM. Categorical data were represented in the form of frequencies and
proportions. Chi-square test was the test of significance. Continuous data were
represented as mean and standard deviation. Independent t-test was used for mean
difference between two groups. P < 0.05 was statistically significant. Results:
Mean sensory onset in Group B was 2.8 +/- 0.7 min, in Group C was 1.4 +/- 0.5
min, and in Group D was 1.2 +/- 0.4 min. Mean sensory regression by two segments
in Group B was 78.5 +/- 9.9 min, in Group C was 136.7 +/- 10.7 min, and in Group
D was 136.4 +/- 11.7 min. Conclusions: alpha2-agonists with hyperbaric
bupivacaine intrathecally have a faster onset of both motor and sensory block. It
also prolongs the duration of analgesia.
PMID- 29962632
TI - Geriatric Patients with Hip Fracture: Frailty and Other Risk Factors Affecting
the Outcome.
AB - Background: Hip fracture is a devastating health-care problem in a geriatric
patient, leading to high mortality and morbidity. Preoperative risk assessment in
the geriatric patient is often inexact because of the difficulty in measuring
their poor physiologic reserves. Aims: The primary objective was to find the
association of modified frailty index (MFI) with 90-day mortality in geriatric
patients who received anesthesia for fractured hip. Secondary objectives were to
assess the association of preoperative waiting time with the 90-day mortality and
the correlation of preexisting medical conditions with poor functional outcome
among the survivors. Settings and Designs: This prospective, observational study
was conducted at a tertiary care institution. Subjects and Methods: In this
prospective observational study, done over a period of 1 year, 60 geriatric
patients aged >=65 years who received anesthesia for fractured hip and fulfilled
selection criteria were recruited. The association of MFI with 90-day mortality
and the correlation of preexisting comorbidities with poor functional outcome
among the survivors were assessed. Statistical Analysis Used: Independent sample
t-test, Mann-Whitney test, and odds ratio were used as applicable. Results: Total
60 patients were available for analysis as two patients dropped off from final 62
on follow up, fifty three patients survived after 90 days. MFI and 90-day
mortality showed a significant direct correlation with P < 0.0001. However, no
association was found between the preoperative waiting time and 90-day mortality.
Preexisting medical conditions showed a significant association of dementia with
total dependence afterward with a P = 0.02. Conclusion: There is significant
statistical correlation of MFI with the 90-day mortality in the geriatric hip
fractured patients undergoing surgery.
PMID- 29962633
TI - An Observational Study for Knowing the Compliance of Patients Scheduled for Major
Abdominal and Thoracic Cancer Surgeries in a Single Specialty Center.
AB - Background: Peri-operative incentive spirometry (IS) helps in improving pulmonary
function, facilitates sputum clearance and prevents unwanted postoperative
pulmonary complications after major abdominal and thoracic surgery. In our
hospital, all patients are instructed to practice IS before abdominal and
thoracic surgeries so that they can perform it in the postoperative period
effectively. However, many patients do not follow our advice. A few unfortunate
patients land up with pulmonary complications as it becomes difficult to train
them after surgery. Aims: To determine the compliance rate of patients who were
instructed to perform incentive spirometry preoperatively. Study design and
settings: Observational, single arm study in a single speciality centre.
Materials and Methods: After approval from hospital ethics committee the study
was registered with Clinical Trials Registry of India (CTRI). 100 patients posted
for major abdominal or thoracic cancer surgery were enrolled in the study. They
were instructed to perform incentive spirometry(IS) in front of relatives, an
information leaflet was provided to them and the spirometry effort was noted in
'ml'. The effort was crossed checked on the day of surgery. Patients performing
IS correctly with effort more or equal to that noted earlier were labelled as
compliant. Others were labelled as non-compliant. The reason of non-compliance
was to be determined using a questionnaire meant for patient and the accompanying
family member. Results: Out of 100, 26 patients were found to be non-compliant
out of which 10 were males and 16 were female patients. 15 patients did not
understand the instructions properly, 8 patients did not get enough time to
practice, family members of 10 patients could not help the patient in performing
and understanding IS, family members of 8 patients did not have adequate time for
the patient. Conclusion: A non-compliance rate of 26% could be because patients
and family members did not understand the seriousness of preoperative IS in spite
of explaining and giving an information leaflet. The surgeries planned were major
ones which require arrangement of finances, abstinence from work and other social
issues like not having anybody at home with other family members, location of
hospital far from the place they live. Involving respiratory therapist and
nursing staff early during pre-anaesthesia check up could help in better
understanding of the patient and family regarding benefits of IS.
PMID- 29962634
TI - A Comparative Study Evaluating Effects of Intravenous Sedation by Dexmedetomidine
and Propofol on Patient Hemodynamics and Postoperative Outcomes in Cardiac
Surgery.
AB - Background: The use of intravenous sedation during cardiac surgery to reduce
awareness has been practised routinely during past few years and the two most
commonly used drugs include propofol and dexmedetomidine, but their effects on
hemodynamics and postoperative outcomes in cardiac surgery is continually being
evaluated. Aims: The aim of this study was to compare the effects of anesthesia
by dexmedetomidine and propofol on the hemodynamic variables and postoperative
outcomes in patients who were planned for elective cardiac surgery. Settings:
Cardiac operating room of a tertiary care hospital. Design: A prospective,
randomized controlled, double-blind clinical trial. Materials and Methods: Sixty
patients were randomized to receive either a continuous infusion of propofol
(0.25-1 mg/kg/h) or dexmedetomidine bolus of 1 MUg/kg over 10 min followed by
infusion (0.2-0.6 MUg/kg/h) after induction of anesthesia. The anesthesia
technique and physiological monitoring including bispectral index monitoring were
similar among both the groups. Hemodynamic variables (mean heart rate [HR], mean
arterial pressure [MAP]) were noted at predefined time intervals, intraoperative
vasopressor or inotrope requirements and postoperative outcomes including
postoperative ventilation time and length of stay in the Intensive Care Unit
(ICU) were also recorded. Statistical Analysis: Statistics was done using SPSS V
20 (IBM, NY) using Student's t-test, analysis of variance, and Mann-Whitney U
test, and a P < 0.05 was considered to indicate a significant difference. Results
and Conclusions: HR and MAP were significantly less in dexmedetomidine group
compared to propofol group (P < 0.05). Both the groups had a similar requirement
of vasopressors and inotropes. The duration of postoperative ventilation and
length of stay in the ICU were significantly shorter in the dexmedetomidine group
(P < 0.05). The risk of delirium was significantly less in dexmedetomidine group
(P < 0.05). From our study we concluded, that the perioperative infusion of
dexmedetomidine produces better hemodynamic stability, reduces the risk of
postoperative delirium, and leads to shorter ICU stay.
PMID- 29962636
TI - Therapeutic Efficacy of Two Different Doses of Dexmedetomidine on the Hemodynamic
Response to Intubation, the Intubating Conditions, and the Effect on the
Induction Dose of Propofol: A Randomized, Double-Blind, Placebo-Controlled Study.
AB - Context: The hemodynamic response associated with laryngoscopy and tracheal
intubation is a common concern for the anesthesiologist, especially in high-risk
patients. The use of dexmedetomidine has found favor in obtunding this response,
in addition to providing better intubating conditions and reducing the dose of
other anesthetic drugs. Most of the current literature states a loading dose of 1
MUg/kg dexmedetomidine to be superior to lower doses in this regard. However,
using a lower dose may be advantageous by reducing incidence of adverse effects
such as hypotension and bradycardia which are likelier with the use of higher
dose, in addition to being more cost-effective. Aims: The aim of the study was
(1) to evaluate and compare the effect of loading doses of 1 MUg/kg and 0.5
MUg/kg dexmedetomidine on attenuation of hemodynamic response to laryngoscopy and
intubation and (2) to evaluate the efficacy of dexmedetomidine in reducing the
induction dose of propofol for achieving better intubating conditions. Materials
and Methods: A randomized, double-blind, placebo-controlled study was planned on
ninety American Society of Anesthesiologists I and II patients scheduled for
elective surgery under general anesthesia. Patients were divided into three
groups. Two groups received different loading doses of dexmedetomidine infusion
before induction and the third group was a control group. The induction dose of
propofol required to abolish the verbal response was noted and compared in all
the three groups. All patients were assessed for the intubating conditions and
hemodynamic response. Statistical Analysis: Nonparametric data were compared
using the Chi-square test and parametric data were compared using Student's t
test using SPSS 16.0 software. Results: Both the loading doses of 1 MUg/kg and
0.5 MUg/kg dexmedetomidine were equally effective in reducing the induction dose
of propofol, improving the intubating conditions and blunting the hemodynamic
response to laryngoscopy and intubation. The incidence of adverse effects such as
hypotension and bradycardia was lesser with the loading dose of 0.5 MUg/kg.
Conclusions: Dexmedetomidine when used as infusion in the loading dose of 0.5
MUg/kg is therapeutically as effective as when used in the dose of 1.0 MUg/kg not
only in reducing the induction dose of propofol but also in providing good
intubating conditions and blunting the hemodynamic response to intubation. A
lower dose is associated with a lesser incidence of adverse effects such as
hypotension and bradycardia.
PMID- 29962635
TI - Postoperative Analgesia with Intrathecal Nalbuphine versus Intrathecal Fentanyl
in Cesarean Section: A Double-Blind Randomized Comparative Study.
AB - Background: Nalbuphine when used as adjuvant to hyperbaric bupivacaine has
improved the quality of perioperative analgesia with fewer side effects. Fentanyl
is a lipophilic opioid with a rapid onset following intrathecal injection. It
does not cause respiratory depression and improves duration of sensory anesthesia
without producing significant side effects. Aim: This study aims to compare the
postoperative analgesia of intrathecal nalbuphine and fentanyl as adjuvants to
bupivacaine in cesarean section. Methodology: A prospective, randomized, double
blind, and comparative study was conducted on 150 parturients of American Society
of Anesthesiologists (ASA) physical status I and II of age group 20-45 years with
normal coagulation profile undergoing cesarean section under spinal anesthesia.
These patients were randomized into three groups with fifty patients in each
group. Group I received 2 ml of 0.5% hyperbaric bupivacaine (10 mg) plus 0.4 ml
nalbuphine (0.8 mg), Group II received 2 ml of 0.5% hyperbaric bupivacaine (10
mg) plus 0.4 ml fentanyl (20 MUg), and Group III received 2 ml of 0.5% hyperbaric
bupivacaine (10 mg) plus 0.4 ml of normal saline. Results: The mean duration of
effective analgesia was 259.20 +/- 23.23 min in Group I, 232.70 +/- 13.15 min in
Group II, and 168.28 +/- 7.55 min in Group III. The mean number of rescue
analgesics required was significantly lower (P < 0.001) in Group I as compared to
Group II and III. Conclusion: Both intrathecal nalbuphine 0.8 mg and fentanyl 20
MUg are effective adjuvants to 0.5% hyperbaric bupivacaine in subarachnoid block.
However, intrathecal nalbuphine prolongs postoperative analgesia maximally and
may be used as an alternative to intrathecal fentanyl in cesarean section.
PMID- 29962637
TI - Comparison of Epidural Bupivacaine and Dexmedetomidine with Bupivacaine and
Fentanyl for Postoperative Pain Relief in Lower Limb Orthopedic Surgery.
AB - Context: Different trials have shown that multimodal analgesia through different
techniques is associated with superior pain relief. Opioids as epidural adjunct
to local anesthetics have been in use for long and alpha2 agonists are being
increasingly used for same. The present study aims at comparing the hemodynamic,
sedative, and analgesic effects of epidurally administered fentanyl and
dexmedetomidine when combined with bupivacaine. Aims: The aim of this study was
to compare the efficacy of epidural dexmedetomidine with bupivacaine versus
epidural fentanyl with bupivacaine for postoperative pain relief. Subjects and
Methods: In this ongoing randomized double-blind study, 70 patients with ASA
physical status classes I and II of either sex between 20 and 60 years scheduled
for lower limb orthopedic surgeries under epidural block were randomly divided
into two Groups (n = 35). After epidural block with 15 ml of 0.5% bupivacaine,
Group I received 1 MUg/kg of fentanyl and Group II received 1 MUg/kg of
dexmedetomidine. Onset and duration of sensory block, motor block, and time to
request for the first postoperative analgesia were recorded. Statistical Analysis
Used: The statistical analysis was performed using SPSS (Statistical Package for
the Social Sciences) Version 15.0 Statistical Analysis Software, Mann-Whitney U
test and Chi-square test. Results: The time to achieve T10 sensory block was
early in Group I (dexmedetomidine) (8.10 + 1.03 min) as compared to Group II
(15.03 + 1.67 min). Onset of motor was earlier in Group I (15.10 + 1.49 min) as
compared to Group II (22.77 + 1.41 min). In Group I (dexmedetomidine), the
majority of patients required 2-3 rescue doses, while in Group II (fentanyl), the
majority of patients required 3-4 rescue doses. Conclusions: Dexmedetomidine
seems to be a better alternative to fentanyl as an epidural adjuvant due to early
onset of sensory anesthesia, prolonged postoperative analgesia, and lower
consumption of rescue analgesia.
PMID- 29962638
TI - Suitability of Nasotracheal Intubation using King Vision and TruviewPCD Video
Laryngoscopes: A Randomized Clinical Trial.
AB - Background: Several video laryngoscopes had demonstrated their superiority over
conventional oral and nasal intubation techniques. King Vision video laryngoscope
has fewer studies supporting its suitability for oral intubations. However, its
suitability as a nasal intubating device has not been yet evaluated. We evaluated
the suitability of King Vision video laryngoscope for nasotracheal intubation
comparing with TruviewPCD. Methods: Eighty American Society of Anesthesiologists
Grade I and II elective surgical patients were studied. After meeting the
inclusion criteria, 80 study subjects were randomized into two groups. Group T
were intubated using TruviewPCD and Group K were intubated with the nonchanneled
King Vision video laryngoscope. Our primary outcome was single successful
nasotracheal intubation without use of any additional maneuvers. The time taken
for intubation, use of additional maneuverers, Cormack-Lehane grading, and
hemodynamics were also analyzed. Results: Seventy-one patients (88.75%) were
successfully intubated in a single attempt, i.e. 35 patients (90%) in Group K and
36 patients (87.5%) in Group T. Intubation time (mean +/- standard deviation) was
67.9 +/- 24.1 s in Group T and 64.9 +/- 20.0 s in Group K where comparison was
not statistically significant (P = 0.5). The additional maneuvers (P = 0.2) and
hemodynamic changes were not clinically significant. There were no associated
serious complications. Conclusion: King Vision video laryngoscope is just as
effective as TruviewPCD video laryngoscope for successful nasotracheal
intubation.
PMID- 29962639
TI - Comparison of Epidural Analgesia Using 0.2% Bupivacaine and 0.2% Ropivacaine for
the Management of Postoperative Pain in Major Orthopedic Surgery.
AB - Introduction: Ropivacaine is preferred over racemic bupivacaine for postoperative
analgesia as it is less cardiotoxic and has high selectivity for sensory fibers.
We aim to compare postoperative epidural analgesia using 0.2% bupivacaine and
0.2% ropivacaine in major lower limb orthopedic surgery. Materials and Methods:
In a prospective, randomized, double-blind study, 100 patients, aged 18-70 years,
undergoing elective major lower limb orthopedic surgery under spinal anesthesia,
were randomly allocated to receive either 7 ml ropivacaine 0.2% (Group R) or 7 ml
bupivacaine 0.2% (Group B) for postoperative analgesia through a lumbar epidural
catheter. The onset and duration of epidural analgesia, total epidural dose
requirement, mean number of epidural topup, rescue analgesia, incidence of motor
blockade, and adverse effects were recorded. Results: No differences were noted
in demographic data and hemodynamic variables in either group. The onset time of
epidural analgesia was 10.46 min +/- 0.68 (Group B) and 10.52 min +/- 0.71 (Group
R). The duration of analgesia was 253.10 +/- 17.46 min (Group B) and 251.80 +/-
15.77 min (Group R). The total analgesic dose requirement was 78.40 mg +/- 6.93
in Group B while in Group R, it was 78.96 mg +/- 6.79. Epidural topup requirement
and the need for rescue analgesia were similar in both the groups. Motor
blockade, hypotension, and nausea were noted more in Group B compared to Group R.
Conclusion: In patients undergoing major lower limb orthopedic surgery under
subarachnoid block, epidural ropivacaine 0.2% produces effective postoperative
analgesia similar to bupivacaine 0.2% with a distinct sensory-motor dissociation
resulting in analgesia without motor blockade.
PMID- 29962640
TI - A Comparison of Acute Physiology and Chronic Health Evaluation III and Simplified
Acute Physiology Score II in Predicting Sepsis Outcome in Intensive Care Unit.
AB - Context: Acute Physiology and Chronic Health Evaluation (APACHE) III and
Simplified Acute Physiology Score (SAPS) II are frequently used to predict the
outcome of Intensive Care Unit (ICU) patients of sepsis. Aim: The aim of the
study was to compare the predictability of outcome with APACHE III and SAPS II
score in ICU patients of sepsis, severe sepsis, and septic shock and the 28-day
mortality. Settings and Design: This study was an observational, prospective
cohort study. Materials and Methods: A total of 100 consecutive patients of
sepsis were studied over 20 months. The worst physiological and biochemical
parameters during the first 24 h were recorded for the scores and the patient's
28-day outcome followed up. Statistical Analysis Used: Continuous data were
expressed as mean +/- standard deviation or median. Receivers operating
characteristic (ROC) curve was used to find the cutoff value, area under the
curve, sensitivity and specificity of APACHE III score, and SAPS II score. Binary
logistic regression with response variable as the outcome was utilized. P < 0.05
was considered statistically significant. Results: The mean APACHE III score in
the survivor group was 66.49 +/- 18.56 as opposed to 80.67 +/- 19.03 for
nonsurvivors. The mean SAPS II score for the survivor group was 43.32 +/- 13.02
as against the nonsurvivor group at 51.92 +/- 12.34. The area under the ROC curve
for APACHE III was 0.711 with 95% confidence interval as against 0.686 for SAPS
II. The best cutoff value obtained for mortality prediction using the ROC curve
was 69 for APACHE III while that for SAPS II was 49. Conclusions: APACHE III was
found to be a better predictor of mortality as compared to SAPS II though the
margin of difference in mortality prediction was not high.
PMID- 29962641
TI - General Anesthesia Using Supraglottic Airway Device in a Myasthenic Patient
Undergoing Reverse Shoulder Arthroplasty.
AB - Myasthenia gravis (MG) is a neuromuscular disorder characterized by weakness and
fatigability of skeletal muscles. The decrease in the number of acetylcholine
receptors results in decreased efficiency of neuromuscular transmission. Although
acetylcholine is released normally, it produces small end-plate potentials that
fail to trigger muscle action potentials. Failure of transmission at many
neuromuscular junctions results in weakness of muscle contraction. This also
makes them susceptible to neuromuscular blocking agents which pose a challenge to
the anesthesiologist. Here, we report a case of a patient who was a known case of
MG posted for reverse shoulder arthroplasty, who was managed using a supraglottic
airway device and spontaneous respiration.
PMID- 29962642
TI - Anesthetic Management for Fracture Head of Radius in a Child with Glutaric
Aciduria type-1.
AB - Glutaric aciduria Type 1 (GA-1) is an autosomal recessive metabolic disorder that
results from deficiency of enzyme glutaryl-CoA dehydrogenase. This gives rise to
elevated neurotoxic glutaric acid and 3-hydroxyglutaric acid as well as nontoxic
glutarylcarnitine in body fluids. The enzyme defect leads to secondary damage to
central nervous system due to the accumulation of glutaric acid. Approximately
90% people will develop the neurological disease during a finite period of brain
development (3-36 months) following an acute encephalopathic crisis often
precipitated by gastroenteritis, immunization, surgical intervention, and
intercurrent febrile illness. GA-1 can also develop insidiously without
clinically apparent crisis in 10%-20% of the patients. We present a 10-year-old
male child with GA-1 who required anesthetic care for fracture (left) neck of
radius. Strategies for anesthetic management should include prevention of
hypoglycemia, dehydration, electrolyte imbalance, and sufficient analgesia to
prevent surgical stress.
PMID- 29962643
TI - Supra-axillary Block: A Novel Ultrasound-Guided Supplement to Brachial Plexus
Block for Surgery Around Elbow.
PMID- 29962644
TI - Incident Reporting of Adverse Drug Reaction to Intravenous Ranitidine in an
Emergency Department.
PMID- 29962645
TI - The Importance of Imaging to Guide Treatment: Intramuscular Psoas Mass with
Lumbosacral Plexopathy.
PMID- 29962646
TI - Effects of Bases and Halides on the Amination of Chloroarenes Catalyzed by
Pd(PtBu3)2.
AB - We report a detailed study of the effects of anions on the rates of the amination
of aryl halides catalyzed by palladium complexes of the hindered
alkylmonophosphine PtBu3. These reactions occur by turnover-limiting oxidative
addition. The extent of the dependence of the rates on the concentration and
identity of bases was found to depend on the electronic properties of the
haloarenes. The rates of reactions of electron-rich and electron-neutral
chloroarenes were independent of the concentration of the bulky alkoxide base
OCEt3-, but they were dependent on the concentrations of the less hindered OtBu-
and the softer 2,4,6-tri-tert-butylphenoxide bases. The reactions were fastest
when 2,4,6-tri-tert-butylphenoxide was used as base and slowest when NaOCEt3 was
used as base. A concurrent reaction pathway involving simultaneous oxidative
addition of chloroarenes to [Pd(PtBu3)] and [(PtBu3)Pd(OR)]- may explain the
dependence of the rates of reactions of electron-rich and electron-neutral
chloroarenes on the identity and concentration of bases. The rates of reactions
of electron-poor chloroarenes and the reactions of bromoarenes were independent
of the concentration of OCEt3-, OtBu-, or 2,4,6-tri-tert-butylphenoxide bases but
were dependent on the identity of bases, even though an adduct of the base did
not accumulate in any observable amounts. Further, long induction periods were
observed for the reactions of electron-poor chloroarenes. These long induction
periods suggest that the complex kinetic behavior could result from the
generation of several catalytically active species.
PMID- 29962647
TI - Correlation between model observers in uniform background and human observers in
patient liver background for a low-contrast detection task in CT.
AB - Channelized Hotelling observer (CHO) has demonstrated strong correlation with
human observer (HO) in both single-slice viewing mode and multi-slice viewing
mode in low-contrast detection tasks with uniform background. However, it remains
unknown if the simplest single-slice CHO in uniform background can be used to
predict human observer performance in more realistic tasks that involve patient
anatomical background and multi-slice viewing mode. In this study, we aim to
investigate the correlation between CHO in a uniform water background and human
observer performance at a multi-slice viewing mode on patient liver background
for a low-contrast lesion detection task. The human observer study was performed
on CT images from 7 abdominal CT exams. A noise insertion tool was employed to
synthesize CT scans at two additional dose levels. A validated lesion insertion
tool was used to numerically insert metastatic liver lesions of various sizes and
contrasts into both phantom and patient images. We selected 12 conditions out of
72 possible experimental conditions to evaluate the correlation at various
radiation doses, lesion sizes, lesion contrasts and reconstruction algorithms.
CHO with both single and multi-slice viewing modes were strongly correlated with
HO. The corresponding Pearson's correlation coefficient was 0.982 (with 95%
confidence interval (CI) [0.936, 0.995]) and 0.989 (with 95% CI of [0.960,
0.997]) in multi-slice and single-slice viewing modes, respectively. Therefore,
this study demonstrated the potential to use the simplest single-slice CHO to
assess image quality for more realistic clinically relevant CT detection tasks.
PMID- 29962648
TI - Emergence of Colorectal Cancer in West Africa: Accepting the Inevitable.
AB - It seems not too long ago that colon and rectal cancer is a "rare" disease in
rural Africa; however, over the last 30 years in West Africa, published evidence
has shown decade by decade increases in the incidence of colorectal cancer (CRC).
Therefore, CRC should now be accepted as a recognized disease in native Africans;
nevertheless, we must acknowledge that the incidence is a fraction of what
obtains in the developed countries of Europe and America. This presentation will
attempt to examine the emergence of CRC within the West African axis over the
last four decades.
PMID- 29962649
TI - Clinical Presentation and Outcome of Sinonasal Tumors in a Nigerian Tertiary
Hospital - 6-year Review.
AB - Background: Sinonasal tumor is an uncommon tumor in Nigeria, but the burden of
the disease in terms of morbidity and mortality is on the increase. The aim of
this study is to evaluate the pattern of presentation and outcome of sinonasal
tumor in our center. Methodology: This was a retrospective review of all the
patients with sinonasal cancer seen in Ear, Nose, and Throat Department of the
hospital between January 2008 and December 2013. The patients' biodata, clinical
presentation, stage of the disease at presentation, identifiable risk factors,
histopathological findings, and outcome were presented. Results: A total of 22
patients were diagnosed with sinonasal cancer out of 71 patients (31%) with
head/neck cancers during the period of study. There were 12 males (54.5%) and 10
females (45.5%) with a mean age of 51 +/- 2.1 years. Epistaxis, nasal blockage,
and discharge were seen in all patients though 41% of patients presented first to
the ophthalmologist due to proptosis. Identifiable risk factors were exposure to
wood dust (29%) and petrochemical products in (11%). Most patients presented
first at advanced stages of the disease (82%). Histologically, well
differentiated squamous cell carcinoma was the most common (54.6%) followed by
nonintestinal well-differentiated adenocarcinoma in 18.2% and plasmacytoma
(9.1%). Chemoradiation was the mainstay of management in (38%) though 13.6% had
total maxillectomy with postsurgical chemoradiation and 50.4% defaulted due to
cost of management. Conclusion: Health education on early presentation and
efforts at early detection of the disease are needed to achieve cure. Exposure to
the identifiable risk factors should be reduced by protective measures. Easy
access to radiotherapy at affordable price will surely improve the outcome of
this disease.
PMID- 29962650
TI - Sexual Functioning and Health-related Quality of Life in Men.
AB - Background: Although erectile dysfunction (ED) is common, little is known about
the impact of ED on the quality of life (QoL) among African men. Materials and
Methods: We used the International Index of Erectile Function (IIEF) to evaluate
ED and the WONCA charts to assess QoL among employees of a university. Results: A
total of 508 men with a mean age of 43 +/- 10 years were studied. IIEF5 scores of
<22 were present in 406 participants (77.9%). Mild ED, mild-to-moderate ED,
moderate ED, and severe ED were present in 34.6%, 26.6%, 10.4%, and 5.7%,
respectively. Systolic and diastolic blood pressure were significantly lower in
those with ED. Marital status, alcohol, cigarette, physical inactivity, obesity,
hypertension, diabetes mellitus, and antihypertensive drug use were not
associated with ED. ED was associated with poor QoL in the domains of social
activities (odds ratio [OR] = 4.35; 95% confidence interval [CI]: 1.01-18.7), and
overall health (OR = 2.27; 95% CI: 1.07-4.82). However, there was no association
of ED with poor QoL in the domains of physical fitness (OR = 1.46; 95% CI: 0.82
2.59), feelings (OR = 1.43; 95% CI: 0.75-2.72), daily activities (OR = 4.72; 95%
CI: 0.61-36.4), and change in health (OR = 1.75; 95% CI: 0.58-5.26). Conclusion:
ED negatively impacts QoL in men.
PMID- 29962651
TI - Pattern of Thyroid Disorders in Children and Adolescents Seen at the Lagos
University Teaching Hospital, Nigeria, Over a 10-year Period.
AB - Introduction: Thyroid disorders account for a large proportion of pediatric
endocrine disorders. Untreated hypothyroidism in childhood has permanent adverse
effects on physical, intellectual, and neurological development. However, few
studies have reported the pattern of pediatric thyroid disorders in Nigeria.
Objectives: The objective of this study was to document the pattern of thyroid
disorders in children and adolescents seen at the Lagos University Teaching
Hospital (LUTH) over a 10-year period. Participants and Methods: This is a
retrospective descriptive study involving children with thyroid disorders seen
from January 1, 2006 to December 31, 2015. Results: Seventy-one patients with
thyroid disorders (0.13%) were seen out of 52,800 new cases (incidence of 1/1000
new cases) comprising 13.4% of 546 pediatric endocrine cases with a male:female
ratio of 1:1.2. Median (range) age at presentation was 1.6 (0.001-14) years.
Congenital hypothyroidism (CH) constituted a major proportion of cases (46.7%),
with a median (range) age at presentation of 9 (1.5-24) months. Down syndrome
constituted 45% of patients with CH with associated congenital heart defects in
eight (53%) patients. Acquired hypothyroidism was seen in ten patients (five
goitrous and five nongoitrous). Six patients had hypothyroidism associated with
multiple anterior pituitary hormone deficiency. Nine patients (all females) had
hyperthyroidism with confirmed Graves' disease in 5 (55.6%), with mean age at
presentation being 9.4 +/- 2.09 years. Other conditions were euthyroid sick
syndrome (2.8%), euthyroid goiter (1.4%), and acute thyroiditis (1.4%). Eight
infants of mothers on treatment for hyperthyroidism ( first seen between the 7th
h of life to 2 months of age) had transient hypothyroidism while one 8-day-old
had transient hyperthyroidism. Conclusion: CH was the most common disorder
encountered with late age at presentation. Routine newborn screening and
maintaining a high index of suspicion are advocated.
PMID- 29962652
TI - Antihypertensive Medicines Prescriptions before and after the Nigeria
Hypertension Society Guidelines and Prescriber's Awareness of the Guideline.
AB - Objectives: The Nigerian hypertension guideline (2005) was based on 1999 ISH/WHO
and the 2003 Sub-Saharan Africa hypertension guidelines. The changes in the
prescribing pattern of physicians before and following the introduction of these
guidelines as well as physicians' awareness of the guidelines in Southern Nigeria
are unknown. Subjects and Methods: A retrospective study of antihypertensive
prescriptions and a cross-sectional descriptive study of the physicians'
awareness of the guidelines. The study was carried out at a tertiary health
facility in Southern Nigeria and reviewed the case records (1999-2008) of 3379
hypertensive patients who had attended the medical outpatient clinic; it also
assessed the awareness of 48 postregistration doctors working in the same
hospital using a self-administered questionnaire. Results: Calcium channel
blockers were the most prescribed class over the entire period (44.7%-69.2%)
while angiotensin-converting enzyme inhibitors prescriptions increased by 325%
(11.8%-51.5%). Annual prescriptions of diuretics increased steadily from 38% in
1999 to a peak of 58% in 2005. A total of 37/48 doctors responded, and a high
proportion (32/37; 86.5%) were aware of the national guidelines, but only 13/37
(35.1%) were satisfied with the recommendations. Diuretics were stated as the
most preferred class of antihypertensive medicines by 26/37 (70.3%) of
respondents. Conclusions: The findings suggest disconnect in the prescribers'
knowledge of recommendations in the guidelines, their stated preferences for
medicines, and the observed findings in the case records. This may be due in part
to the observed dissatisfaction of doctors with the guidelines.
PMID- 29962653
TI - Determinants of Crystalluria among Type 2 Diabetes Patients; A Case-Control Study
of the Agona West Municipality, Ghana.
AB - Background/Aim: Type 2 diabetes mellitus (T2DM) has been implicated as a risk
factor for nephrolithiasis. The aim of this study was to determine the prevalence
and types of crystalluria among individuals with T2DM. It further sought to
identify associated risks, which could influence crystalluria. Methods: A case
control study with random sampling of 165 diabetes patients (cases) and 40
healthy non-diabetics (controls) was conducted from December 2012 to May 2013 at
the Agona Swedru Municipal Hospital, Ghana. Sociodemographic and anthropometric
data were obtained from the participants. Blood and urine samples were collected
for the estimation of blood glucose (fasting) and urinalysis for the presence of
crystals, respectively (light microscopy). Results: Overall frequency of
crystalluria was 18.0%. The prevalence of urine crystals in diabetics (17.5%) was
more than that in non-diabetics (5.0%). Types of crystals found in the T2DM
patients by prevalence were calcium oxalate (12.7%), uric acid (3.6%), and
tyrosine (1.2%). Mean age, body mass index, systolic blood pressure, and fasting
blood glucose (FBG) were higher among case participants than in controls (P <
0.001; P < 0.001; P = 0.018; P < 0.001). Case participants had a lower urine pH
than the controls (P < 0.001). Crystalluria was positively correlated with FBG (P
= 0.002) and negatively with urine pH (P = 0.108). On multivariate analysis, FBG
was independently associated with crystalluria (P = 0.002), after adjustment for
other factors. Conclusion: Crystalluria is common in diabetes patients. Acidic
urine pH is mostly seen in T2DM and may be a predisposing factor to crystalluria.
Good glycemic control may be a helpful in reducing the occurrence of crystalluria
among T2DM.
PMID- 29962654
TI - Purple Urine Bag Syndrome in an 80-year-old Female Cameroonian.
AB - Purple urine bag syndrome is a rare clinical entity commonly seen in elderly
females with a long-term urinary catheterization. It presents as purple
discoloration of the patient's plastic urine bag and tubing. We report the first
case of this rare entity from Central Africa. We present the case of an 80-year
old female with purple urine associated with signs of urinary tract infection.
Her symptoms resolved after 3 days of intravenous antibiotic treatment and diet
modification. Purple urine bag syndrome remains rare, especially in African
literature. Awareness of this benign syndrome is necessary for clinicians so as
to adequately manage up to and including the associated anxiety.
PMID- 29962655
TI - Job Insecurity: Differential Effects of Subjective and Objective Measures on Life
Satisfaction Trajectories of Workers Aged 27-30 in Germany.
AB - Job insecurity has become increasingly evident in European countries in recent
years. In Germany, legislation has increased insecurity through erosion of the
standard employment relationship. Fixed-term contracts are central to definitions
of insecurity based on atypical or precarious work but there is still limited
understanding of what creates insecurity and how it affects workers. Drawing on
Bourdieu's thesis that "insecurity is everywhere", the relationships between
subjective and objective measures of insecurity are examined for their impact on
the 5-year trajectories of life satisfaction of men and women in the age group 27
30. Latent growth curve analysis of data from the German Socio-Economic Panel for
2010-2014 highlights the adverse and lasting effects of subjective concerns about
job insecurity on life satisfaction trajectories. This association cuts across
educational groups, with far reaching implications as subjective concerns about
job security permeate young worker's lives well beyond the objective condition of
being employed on a fixed-term contract.
PMID- 29962656
TI - Comparing Life Satisfaction of Immigrants and Natives Across Europe: The Role of
Social Contacts.
AB - Research on immigrants' assimilation is widespread both in the U.S. and Europe.
While it has been extensively studied how immigrants fare compared to natives on
socio-economic indicators, few studies have focussed on immigrants' perception of
their position. In this paper we focus on comparing life satisfaction of
immigrants and natives across Europe and on the role of social embeddedness.
Using data from the first six rounds (2002-2012) of the European Social Survey, a
repeated cross-sectional survey, we find that life satisfaction among immigrants
is lower than among natives even though differences diminish over generations.
For first generation immigrants part of the life satisfaction gap is explained by
the lower level of social embeddedness they have compared to natives. We also
find that social embeddedness is a key explanatory factor for life satisfaction
for both immigrants and natives. For two out of the three indicators of social
embeddedness that we consider we however find different patterns of association
with life satisfaction for immigrants compared to natives.
PMID- 29962657
TI - Sparse canonical correlation analysis between an alcohol biomarker and self
reported alcohol consumption.
AB - In investigating the correlation between an alcohol biomarker and self-report, we
developed a method to estimate the canonical correlation between two high
dimensional random vectors with a small sample size. In reviewing the relevant
literature, we found that our method is somewhat similar to an existing method,
but that the existing method has been criticized as lacking theoretical grounding
in comparison with an alternative approach. We provide theoretical and empirical
grounding for our method, and we customize it for our application to produce a
novel method, which selects linear combinations that are step functions with a
sparse number of steps.
PMID- 29962658
TI - An evaluation of common methods for dichotomization of continuous variables to
discriminate disease status.
AB - Dichotomization of continuous variables to discriminate a dichotomous outcome is
often useful in statistical applications. If a true threshold for a continuous
variable exists, the challenge is identifying it. This paper examines common
methods for dichotomization to identify which ones recover a true threshold. We
provide mathematical and numeric proofs demonstrating that maximizing the odds
ratio, Youden's statistic, Gini Index, chi-square statistic, relative risk and
kappa statistic all theoretically recover a true threshold. A simulation study
evaluating the ability of these statistics to recover a threshold when sampling
from a population indicates that maximizing the chi-square statistic and Gini
Index have the smallest bias and variability when the probability of being larger
than the threshold is small while maximizing Kappa or Youden's statistics is best
when this probability is larger. Maximizing odds ratio is the most variable and
biased of the methods.
PMID- 29962659
TI - Assembling the Dead, Gathering the Living: Radiocarbon Dating and Bayesian
Modelling for Copper Age Valencina de la Concepcion (Seville, Spain).
AB - The great site of Valencina de la Concepcion, near Seville in the lower
Guadalquivir valley of southwest Spain, is presented in the context of debate
about the nature of Copper Age society in southern Iberia as a whole. Many
aspects of the layout, use, character and development of Valencina remain
unclear, just as there are major unresolved questions about the kind of society
represented there and in southern Iberia, from the late fourth to the late third
millennium cal BC. This paper discusses 178 radiocarbon dates, from 17 excavated
sectors within the c. 450 ha site, making it the best dated in later Iberian
prehistory as a whole. Dates are modelled in a Bayesian statistical framework.
The resulting formal date estimates provide the basis for both a new
epistemological approach to the site and a much more detailed narrative of its
development than previously available. Beginning in the 32nd century cal BC, a
long-lasting tradition of simple, mainly collective and often successive burial
was established at the site. Mud-vaulted tholoi appear to belong to the 29th or
28th centuries cal BC; large stone-vaulted tholoi such as La Pastora appear to
date later in the sequence. There is plenty of evidence for a wide range of other
activity, but no clear sign of permanent, large-scale residence or public
buildings or spaces. Results in general support a model of increasingly
competitive but ultimately unstable social relations, through various phases of
emergence, social competition, display and hierarchisation, and eventual decline,
over a period of c. 900 years.
PMID- 29962660
TI - The 2015/2016 El Nino Event in Context of the MERRA-2 Reanalysis: A Comparison of
the Tropical Pacific with 1982/1983 and 1997/1998.
AB - The 2015/2016 El Nino is analyzed using atmospheric/oceanic analysis produced
using the Goddard Earth Observing System (GEOS) data assimilation systems. As
well as describing the structure of the event, a theme of the work is to compare
and contrast it with two other strong El Ninos, in 1982/1983 and 1997/1998. These
three El Nino events are included in the Modern-Era Retrospective analysis for
Research and Applications (MERRA) and in the more recent MERRA-2 reanalyses.
MERRA-2 allows a comparison of fields derived from the underlying GEOS model,
facilitating a more detailed comparison of physical forcing mechanisms in the El
Nino events. Various atmospheric/oceanic structures indicate that the 2015/2016
El Nino maximized in the Nino3.4 region, with the large region of warming over
most of the Pacific and Indian Ocean. The eastern tropical Indian Ocean, Maritime
Continent, and western tropical Pacific are found to be less dry in boreal
winter, compared to the earlier two strong events. While the 2015/2016 El Nino
had an earlier occurrence of the equatorial Pacific warming and was the strongest
event on record in the central Pacific, the 1997/1998 event exhibited a more
rapid growth due to stronger westerly wind bursts and Madden-Julian Oscillation
during spring, making it the strongest El Nino in the eastern Pacific. Compared
to 1982/1983 and 1997/1998, the 2015/2016 event has a shallower thermocline over
the eastern Pacific with a weaker zonal contrast of sub-surface water
temperatures along the equatorial Pacific. While the three major ENSO events have
similarities, each are unique when looking at the atmosphere and ocean surface
and sub-surface.
PMID- 29962661
TI - Differential Identification of Females and Males with Reading Difficulties: A
Meta-Analysis.
AB - : Males are more likely than females to be identified as having reading
difficulties, but it is unclear if this is a result of sample ascertainment or
identification bias. The purpose of this meta-analysis was to determine the
magnitude of gender differences in reading difficulties using available studies
in which researchers investigated this difference and an additional dataset with
a representative U.S. SAMPLE: After conducting a literature search, sixteen
studies and a restricted use dataset were included in the present analysis (N =
552,729). A random-effects odds ratio (OR) model indicated that males are 1.83
times more likely than females to have reading difficulties. Moderator analyses
revealed that the gender ratio is greater when the identified reading
difficulties were more severe. Further, this difference in identification rates
across males and females was found without evidence of publication bias.
Implications for the identification of students with reading difficulties are
discussed.
PMID- 29962663
TI - The Gendered Experience of Smoking Stigma: Implications for Tobacco Control.
AB - Tobacco denormalization is a widely accepted tobacco control strategy, shaping
policies and programs throughout the United States as well as globally. In spite
of widespread beliefs about the effectiveness of tobacco denormalization
approaches, concerns about their emphasis on stigmatization have emerged. Social
science research on smoking stigma raises questions about the potential
iatrogenic consequences of tobacco denormalization approaches. Few studies have
considered how smoking stigma may be internalized differently by different
people, particularly those who experience stigmatization because of other
socially-ascribed makers of inequity (e.g. race, ethnicity, gender, sexuality).
The intersection of multiple stigmas may work to intensify the "social isolation
and marginalization" that some people already experience (Greaves & Hemsing 2009;
pg S127). This paper presents results from a pattern-level analysis of focus
group and interview data from a study investigating smoking-related stigma and
perceptions of tobacco denormalization approaches among 15 low income Black women
who smoke in the San Francisco Bay Area. Our analysis revealed a cycle where
Black women's experiences with structural oppression resulted in stress and the
use of cigarettes to cope with that stress. Though the connection between smoking
and stress is well documented in previous research, our analysis further revealed
the additional contribution of the stigmatization of smoking and how it
intensifies inequity for Black women who smoke. Implications of these findings
for tobacco control and prevention are discussed.
PMID- 29962665
TI - Two-year performance study of porous, thermoset, shape memory polyurethanes
intended for vascular medical devices.
AB - The long-term shape-recovery behavior of shape memory polymers has often been
shown to be dependent on the length of time the material has been stored in the
secondary shape. Typically, recovery performance and shape fixity will decrease
with increased time in the secondary shape. In medical materials, a shelf-life is
crucial to establish as it sets the upper threshold for device performance in a
clinical setting, and a reduction in shape recovery would limit the development
of SMP medical devices. Here, we present a two-year study of strain recovery,
strain fixity, and shape recovery kinetics for passively and actively actuated
SMPs intended for vascular devices. While kinetic experiments using immersion DMA
indicate slight material relaxation and a decrease in the time to recovery, these
changes are not found for bulk recovery experiments. The results indicate that a
two-year shelf-life for these SMPs is very reasonable, as there is no change in
the recovery kinetics, strain recovery, or strain fixity associated with this
aging time. Further, a thermal accelerated aging test is presented for more rapid
testing of the shape memory behavior of these SMPs and is compared with the real
time aging results, indicating that this test is a reasonable indicator of the
two-year behavior.
PMID- 29962664
TI - Naturalistic Decision Making in After-Action Review Meetings: The Implementation
of and Learning from Post-Fall Huddles.
AB - The purpose of this study was to add to our understanding of Naturalistic
Decision Making (NDM) in healthcare, and how After Action Reviews (AARs) can be
utilized as a learning tool to reduce errors. The study focused on the
implementation of a specific form of AAR, a post-fall huddle, to learn from
errors and reduce patient falls. Utilizing 17 hospitals that participated in this
effort, information was collected on 226 falls over a period of 16 months. The
findings suggested that the use of self-guided post-fall huddles increased over
the time of the project, indicating adoption of the process. Additionally, the
results indicate that the types of errors identified as contributing to the
patient fall changed, with a reduction in task and coordination errors over time.
Finally, the proportion of falls with less adverse effects (such as non-injurious
falls) increased during the project time period. The results of this study fill a
void in the NDM and AAR literature, evaluating the role of NDM in healthcare
specifically related to learning from errors. Over time, self-guided AARs can be
useful for some aspects of learning from errors.
PMID- 29962666
TI - Dialysis Catheter: "Love-Hate Relationship".
PMID- 29962662
TI - Autobiography of James S. Hyde.
AB - The papers, book chapters, reviews, and patents by James S. Hyde in the
bibliography of this document have been separated into EPR and MRI sections, and
within each section by topics. Within each topic, publications are listed
chronologically. A brief summary is provided for each patent listed. A few
publications and patents that do not fit this schema have been omitted. This list
of publications is preceded by a scientific autobiography that focuses on
selected topics that are judged to have been of most scientific importance.
References to many of the publications and patents in the bibliography are made
in the autobiography.
PMID- 29962667
TI - Carbamylated Hemoglobin can Differentiate Acute Kidney Injury from Chronic Kidney
Disease.
AB - Carbamylated hemoglobin (CarHb) was found to have a potential role in the
differentiation of patients with acute kidney injury (AKI) from chronic kidney
disease (CKD). This study was aimed at the evaluation of the diagnostic
performance and usefulness of CarHb in the differentiation of AKI from CKD. Forty
patients with renal disease and twenty age- and sex-matched healthy controls were
included in the study. Urea, creatinine, Hb, and CarHb were measured in all the
subjects. Patients with AKI and CKD were found to have significantly increased
levels of CarHb when compared to controls (P < 0.05 for both groups). Patients
with CKD had significantly increased levels of CarHb when compared to patients
with AKI (P < 0.05). CarHb showed significant positive correlation with urea in
patients with renal disease (r = 0.776, P < 0.0001). Significant area under curve
(AUC = 0.840, P < 0.0001) was obtained for CarHb and a cut-off value of 98.33 MUg
VH/g Hb resulted with the best combination of 85% sensitivity and 75%
specificity. CarHb may provide clinical utility since patients with AKI and CKD
have similar clinical presentation usually. A cut-off value of 98.33 MUg VH/g Hb
has been found to be useful to differentiate AKI from CKDs.
PMID- 29962669
TI - Interpretation of Kidney Biopsy in Indian Patients Older than 60 Years: A
Tertiary Care Experience.
AB - The adult population above the age of 60 years has significantly increased in
India, with a life expectancy of 68.4 years in 2016. Data regarding the renal
histopathology in these patients are scarce though the number of native kidney
biopsies done in this subset of population is increasing. The present study is a
retrospective analysis of 231 biopsies from a total of 700 biopsies, from
patients above 60 years of age (M = 65.8%; F = 34.2%) with a mean age of 64 +/-
6.03 years. The indications for kidney biopsy included nephrotic syndrome (NS)
(30.4%), nephritic syndrome (19.1%), rapidly progressive renal failure (11.7%),
acute kidney injury (AKI) (15.7%), and acute worsening of preexisting chronic
kidney disease (CKD) (23%). The median percentage of glomerulosclerosis was 22%
(5%-45%), and interstitial fibrosis and tubular atrophy was 30% (10%-50%). The
most common cause for nephrotic syndrome was membranous nephropathy (31.4%) and
for nephritic syndrome was benign arterionephrosclerosis (22.7%). Postinfectious
glomerulonephritis (29.6%) was the leading cause for rapidly progressive renal
failure. Acute injury on CKD was notable in patients with diabetic nephropathy
(30.2%). The predominant causes for AKI were acute tubulointerstitial nephritis
(33.3%), acute tubular necrosis (22.2%), and acute pyelonephritis (19.4%). The
biopsy proven histopathological features enabled us in tailoring the therapy.
None of the patients developed life-threatening complications following
ultrasonography-guided biopsy.
PMID- 29962668
TI - Distribution of Virulence Factors According to Antibiotic Susceptibility among
Escherichia coli Isolated from Urinary Tract Infection.
AB - Escherichia coli is the major causative pathogen of urinary tract infection (UTI)
in humans. Virulence and drug resistance play important roles in the pathogenesis
of E. coli infections. The aims were to investigate the presence of uropathogenic
virulence genes and to evaluate a relationship between antibiotic resistance and
virulence in E. coli from UTI. A total of 132 E. coli were collected between
April and June 2015 in two hospitals of Sanandaj, Iran. Isolates were examined
for susceptibility to 16 antibiotic disks using the disk diffusion method and for
possession of virulence genes by polymerase chain reaction. Associations between
antimicrobial resistance and virulence genes were investigated. A P < 0.05 was
considered significant. Of the 132 isolates, the most prevalent virulence gene
was pap (31.1%), followed by cnf (28.8%), hly (16.7%), and afa (10.6%). Different
patterns of virulence genes were identified. A significant association was
detected between the simultaneous presence of hly and pap. The most effective
antibiotics were nitrofurantoin, cefoxitin, and imipenem and the least effective
were ampicillin, trimethoprim-sulfamethoxazole, and cefotaxime. An association
was seen between the presence of cnf and susceptibility to the certain
antibiotics, whereas strains with a reduced susceptibility to the certain
antibiotics were associated with a significantly increased prevalence of afa and
hly (P < 0.05). These findings suggest a correlation between the presence of
virulence gene and resistance in E. coli strains from UTI. The results indicate
that there is a need for surveillance programs to monitor drug resistance in
pathogenic E. coli.
PMID- 29962670
TI - Adrenocortical Suppression in Children with Nephrotic Syndrome Treated with Low
Dose Alternate Day Corticosteroids.
AB - Corticosteroids form the mainstay of therapy for all forms of nephrotic syndrome.
The long-term use of this medication is associated with serious side effects
including adrenocortical suppression. The primary objective of this study was to
identify adrenocortical suppression (assessed by single morning serum cortisol
levels) in children with nephrotic syndrome on treatment with low-dose alternate
day steroids. This cross-sectional study was conducted in the Department of
Pediatrics in a tertiary care hospital from January 2014 to January 2015. Seventy
children (1-18 years) with nephrotic syndrome (steroid sensitive and resistant)
who were in remission and on low-dose alternate day steroids for at least 8 weeks
or had received steroids of 2 mg/kg/d for at least 2 weeks in the last 1 year
(infrequent relapsers) were enrolled. Relevant history was taken, clinical
examination was done and blood samples were drawn for serum cortisol, lipid
profile, kidney function tests, fasting blood sugar, glycated hemoglobin (HbA1c),
and serum albumin. Forty percent (28/70) children had adrenocortical suppression
as assessed by low morning serum cortisol levels. The mean serum cortisol levels
were 188 nmol/L and were significantly lower in frequently relapsing individuals
(85.9 nmol/L) as compared to other types of nephrotic syndrome (P = 0.05). The
prevalence of adrenocortical suppression was higher in steroid-resistant patients
(57%) as compared to 28% in frequently relapsing and 11% in steroid-dependent
patients. Fifty-seven percent of patients with adrenocortical suppression had
short stature while 50% had obesity. All individuals had normal serum HbA1c
levels. The cumulative steroid doses and total duration of corticosteroid therapy
were significantly higher in patients with adrenocortical suppression. Children
with nephrotic syndrome treated with low-dose alternate day steroids have a high
prevalence of adrenocortical suppression on screening with single morning
cortisol sample. Those with frequently relapsing or steroid-resistant diseases
are at a higher risk of suppression.
PMID- 29962671
TI - Spectrum of IgG4-related Kidney Disease at a Tertiary Care Center.
AB - IgG4-related kidney disease (IgG4 RKD) is increasingly reported with varied
manifestations. The present study was carried out to study the spectrum of IgG4
RKD. All patients with renal manifestation associated with conditions known to be
associated with IgG4-related diseases (IgG4 RDs), or renal imaging or histology
suggestive of IgG4 RKD were included and evaluated further. Patients with known
extrarenal IgG4RD were also screened for renal involvement. Out of 40 patients
screened over a period of 15 months, IgG4 RKD was diagnosed in 8. Majority were
male (87.5%) with mean age being 56 years. Disease spectrum ranged from normal
renal function in one to renal failure requiring dialysis in another two
patients. Significant proteinuria was uncommon (12.5%) while hematuria was not
seen in any patient. Tubulointerstitial nephritis was seen in all four patients
who underwent kidney biopsy. Two patients had associated glomerular lesions in
the form of immune complex crescentic glomerulonephritis. The most common imaging
abnormality was hypodense renal lesions seen in 2 patients. Elevated IgG4 levels
had 87.5% sensitivity and 78.3% specificity for IgG4 RKD and levels did not
correlate with disease severity. Of 4 patients treated with steroids, 3 showed
improvement in renal function. IgG4 RKD is an uncommon disease even at a referral
tertiary care center. Elevated IgG4 levels alone are neither sensitive nor
specific for the diagnosis of IgG4 RKD, and a combination of clinical, imaging,
serological, and histological features are required for diagnosis.
PMID- 29962672
TI - The Spectrum of Focal Segmental Glomerulosclerosis from Eastern India: Is It
Different?
AB - Focal segmental glomerulosclerosis (FSGS) is a disease that is defined entirely
by its histopathological appearance. The recent Columbian classification has
grouped this disease into various types based on the light microscopic
description. There is a paucity of data describing the distribution of its
various subtypes from the Indian subcontinent. This study was undertaken with the
aim to throw light on the epidemiology and clinical features of primary FSGS in
Eastern India. This retrospective study includes our cohort of biopsy-proven FSGS
who presented to us from June 2009 to July 2011 and the analysis of their
presenting clinical and histopathological features from our center in East India.
Out of 347 patients diagnosed with FSGS in this period, 224 patients were
included in the study. A total of 167 cases were of not otherwise specified (NOS)
variant (74.5%), 30 tip variant (13.39%), 14 perihilar (6.25%), 8 cellular
(3.57%), and 5 to the collapsing variant (2.23%). The maximum proteinuria at
presentation was seen with the tip variant (7.98 +/- 6.6 g/24 h), and the renal
functions were most deranged at presentation with the collapsing variant. These
findings were different from those described in other populations including
higher prevalence of the tip and the perihilar variant, significant difference in
the degree of hypertension, proteinuria, and renal dysfunction among the
different variants. The Columbian classification has helped to stratify the
outcomes of this glomerular disease with respect to its clinical presentation as
well as histopathological features. However, the characteristics of the various
variants do show a distinctive pattern in various populations based on
ethnicities.
PMID- 29962674
TI - Rare Association of Waardenburg Syndrome with Minimal Change Disease.
AB - Waardenburg syndrome (WS) is a rare genetic disorder characterized by varying
degrees of hearing loss, pigmentary anomalies, and defects of other neural crest
cell-derived structures. The association of WS with renal anomalies has been
described in the literature. However, nephrotic syndrome is a very rare
association with WS, and only one case has been reported in the literature. We
report a case of WS2 associated with biopsy-proven nephrotic syndrome (minimal
change disease).
PMID- 29962675
TI - Monoclonal Gammopathy of Renal Significance Presenting as Cryoglobulinemic
Glomerulonephritis: A Case Report and Review of Literature.
AB - Monoclonal gammopathy of renal significance (MGRS) can present with myriad of
morphological features. We report a case of MGRS in a 46-year-old man who
presented with nephrotic-range proteinuria and renal insufficiency. Renal biopsy
showed amorphous eosinophilic periodic acid-Schiff positive deposits in capillary
loops and lamda light chain positivity on immunofluorescence, suggestive of
cyoglobulinemic glomerulonephritis. Serum cryoglobulins were positive. Serum
immunoelectrophoresis and immunofixation showed a M band of 0.5 g/dl of IgG
lambda type. Bone marrow showed 8% of plasma cells which confirmed the diagnosis
of MGRS.
PMID- 29962673
TI - Direct-acting Antiviral Agents in Hepatitis C Virus-infected Renal Allograft
Recipients: Treatment and Outcome Experience from Single Center.
AB - Hepatitis C virus (HCV) infection in renal allograft recipient is associated with
increased morbidity and mortality. At present, only few studies related to
treatment and outcomes of HCV-infected renal allograft recipients with DAAs have
been published. We aimed the study to assess the efficacy and safety of
sofosbuvir-based regimens in HCV-infected renal allograft recipients. We analyzed
data of 22 eligible HCV-infected renal allograft recipients (14 genotype-3, 6
genotype-1, one each genotype-2 and 4) who were treated with DAAs at our
institute. DAA regimen included sofosbuvir and ribavirin with or without
ledipasvir or daclatasvir for 12-24 weeks. Patients were followed up for 24 weeks
after completion of treatment. A rapid viral response of 91%, end of therapy
response of 100%, and sustained viral response at 12 and 24 weeks of 100% with
rapid normalization of liver enzymes were observed. Therapy was well tolerated
except for ribavirin-related anemia. A significant decrease in tacrolimus trough
levels was observed and most patients required increase in tacrolimus dose during
the study. Treatment with newer DAAs is effective and safe for the treatment of
HCV-infected renal allograft recipients.
PMID- 29962676
TI - Mucormycosis of the Thyroid Gland: A Cataclysmic Event in Renal Allograft
Recipient.
AB - Invasive fungal infection is a complication seen in immunocompromised patients. A
disseminated fungal infection has a high rate of mortality. Although disseminated
infection is known to be seen in most organs, thyroid involvement is rarely
reported. Hence, we report a fatal case of thyroid mucormycosis which resulted
into laryngeal nerve paralysis and death of a renal allograft recipient.
PMID- 29962677
TI - Portal Vein Thrombosis: A Rare Complication of Nephrotic Syndrome.
AB - Deep vein thrombosis, renal vein thrombosis, and cerebral venous sinus thrombosis
in children are frequently described complications of nephrotic syndrome (NS).
Early diagnosis and treatment with anticoagulants is the key for a good outcome.
There are a few reported cases of portal vein and superior mesenteric thrombosis
in adults in association with NS. Here, we describe two cases of portal vein
thrombosis with variable extent of involvement of superior mesenteric vein in
association with relapse of NS. A high degree of suspicion, ultrasonography of
the abdomen along with Doppler study of abdominal vessels, and computed
tomography angiography can only pick up such unusual sites of thrombosis and
facilitate early management.
PMID- 29962678
TI - Hidden in Plain Sight: An Unusual Cause of Rapidly Progressive Renal Failure.
AB - Hyperoxaluria and resultant oxalate nephropathy are infrequently reported causes
of irreversible renal failure. A rapid decline in renal function in an otherwise
insidiously progressive oxalate nephropathy may be triggered by various
superimposed insults like the use of nephrotoxic drugs. We present the case of a
patient with rapidly progressive renal failure due to oxalate nephropathy that
lead to a retrospective diagnosis of chronic pancreatitis. This case highlights
the importance of timely assessment for enteric hyperoxaluria in patients with
unexplained renal failure of tubulointerstitial nature.
PMID- 29962679
TI - Perinuclear Antineutrophil Cytoplasmic Antibody Positive Glomerulonephritis in a
Case of Limited Cutaneous Scleroderma.
AB - Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis in a
patient of scleroderma is very rare. Very few cases have been reported in English
literature. We report a case of a 58-year-old male with long-standing limited
cutaneous scleroderma (Scl-70 positive) presenting with normotensive scleroderma
renal crisis. Perinuclear ANCA with antimyeloperoxidase antibody was found to be
strongly positive. Renal biopsy showed pauci immune-necrotizing crescentic
glomerulonephritis. We believe that this case report will be helpful in
understanding clinical features of normotensive ANCA-associated
glomerulonephritis in scleroderma patients.
PMID- 29962680
TI - Pulmonary Thromboembolism: A Rare but Serious Complication of Nephrotic Syndrome.
PMID- 29962681
TI - Essential Thrombocythemia Presenting as Paraneoplastic Glomerulonephritis.
PMID- 29962682
TI - Cholemic Nephrosis from Acute Hepatitis E Virus Infection: A Forgotten Entity?
PMID- 29962683
TI - Kimura's Disease Presenting as Proliferative Glomerulonephritis with Complete
Heart Block.
PMID- 29962684
TI - Dosimetric Comparison of Irregular Surface Compensator and Field-in-Field for
Whole Breast Radiotherapy.
AB - Purpose: The purpose of the present study was to evaluate the dosimetric benefits
of the irregular surface compensator (ISC) technique for whole breast
radiotherapy compared with the field-in-field (FIF) technique. Materials and
Methods: Radiotherapy was planned using both techniques in 50 breast cancer
patients (25 left sided and 25 right sided). The Eclipse treatment planning
system (Varian Medical Systems) was used for dose calculations. For the FIF
technique, subfields were added to the main fields to reduce hot and cold
regions; for the ISC technique, the fluence editor application was used to extend
the optimal fluence. Planning target volume dose, dose homogeneity index (DHI),
maximum dose, ipsilateral lung, and heart doses for the left breast irradiation
and monitor unit (MU) counts required for treatment were compared between the two
techniques. Results: Compared with the FIF technique, the ISC technique
significantly decreased DHI values and volumes receiving >105% of the
prescription dose, and increased volumes receiving >95% of the dose and MU count
(P < 0.01 for all comparisons). For the heart and ipsilateral lung, the FIF
technique significantly reduced volumes receiving >5 Gy compared with the ISC
technique (P < 0.01); however, volumes receiving >10, 20, and 30 Gy and the
values of a mean dose did not differ significantly between the techniques (P >
0.05). Conclusions: The ISC technique is preferred over the FIF technique.
PMID- 29962685
TI - Radiation Dose Measurements in a 256-Slice Computed Tomography Scanner.
AB - Purpose: The purpose of this study is to compare computed tomography (CT)
radiation dose measurement methods proposed by TG111, International
Electrotechnical Commission (IEC), and a direct dose profile integral (DPI)
measurement method. Methods: Pencil and Farmer ion chambers are used for
integrating dose profiles at different beam widths in a 60 cm long body phantom.
Resulting DPI is used to calculate CT dose index (CTDI) at each beam width.
Measurements are also done for a pencil chamber inserted into a 15 cm body
phantom at the reference beam width. The reference measurement is scaled with
pencil chamber measurements in air at different beam widths, according to the IEC
approach. Finally, point dose measurements are done with a Farmer chamber under
equilibrium conditions according to the TG111 method. All CTDIs calculated from
measured data are compared to the scanner displayed CTDIs. Results: Calculated
CTDIs, at different beam widths, using the IEC approach are within 20% of CTDIs
calculated from DPI measurements in a 60 cm long body phantom. Dose Length
Integral (DLI) obtained from TG111 method is close to the results obtained from
DPI measurements. Scanner displayed CTDIs are lower than all measured values by
up to 38% at the techniques used. Conclusion: Although the IEC method is the
easiest to use compared to the TG111 and direct DPI measurement method, it
underestimates dose indices by about 20%. CTDIs displayed on the GE scanner are
lower than those measured in this study by up to 38%.
PMID- 29962686
TI - Validation of a Software Upgrade in a Monte Carlo Treatment Planning System by
Comparison of Plans in Different Versions.
AB - Purpose: Validation of a new software version of a Monte Carlo treatment planning
system through comparing plans generated by two software versions in volumetric
modulated arc therapy (VMAT) for lung cancer. Materials and Methods: Three
patients who were treated with 60 Gy/30 fractions in Elekta SynergyTM linear
accelerator by VMAT technique with 2% statistical uncertainty (SU) were chosen
for the study. Multiple VMAT plans were generated using two different software
versions of Monaco treatment planning system TPS (V5.10.02 and V5.11). By keeping
all other parameters constant, originally accepted plans were recalculated for
the SUs of 0.5%, 1%, 2%, 3%, 4%, and 5%. For plan evaluation, the metrics
compared were conformity Index (CI), homogeneity Index (HI), dose coverage to
planning target volume (PTV), organ at risk (OAR) doses to spinal cord,
pericardium, bilateral lungs-PTV, esophagus, liver, normal tissue integral dose
(NTID), volumes receiving dose >5 and >10 Gy, calculation time (tCT), and gamma
pass rates. Results: In both versions, CI and HI improved as the SU increased
from 0.5% to 5%. No significant dose difference was observed in Dmean to PTV,
bilateral lungs-PTV, pericardium, esophagus, liver, normal tissue volume
receiving >5, and >10 Gy and NTID. It was observed that while the tCT and gamma
pass rates decreased, the maximum dose to PTV increased as the SU increased. No
other significant dose differences were observed between the two MC versions
compared. Conclusion: For lung VMAT plans, in both versions, SU could be accepted
up to 3% per plan with reduced tCT without compromising plan quality and
deliverability by accepting variations in point dose and an inhomogeneous dose
within the target. The plan quality of MonacoTMV5.10.02 was similar to
MonacoTMTPS-V5.11 except for tCT.
PMID- 29962687
TI - A Homogeneous Water-Equivalent Anthropomorphic Phantom for Dosimetric
Verification of Radiotherapy Plans.
AB - Water is treated as radiological equivalent to human tissue. While this seems
justified, there is neither mathematical proof nor sufficient experimental
evidence that a water phantom can be treated as equivalent to human tissue. The
aim of this work is to simulate and validate a water phantom that is tissue
equivalent in terms of the dosimetric characteristics of both water and human
tissue Dynamic, intensity-modulated radiotherapy plans for two head and neck, one
brain, one pelvis, and three lung/mediastinum cases were chosen for this study.
Using a treatment planning system (TPS) (Eclipse, Varian Medical System, Polo
Alto, CA, USA) and Anisotropic Analytic Algorithm in a grid resolution of 5 mm *
5 mm, a patient-equivalent water phantom was calculated from all rays in the
isocentric plane as an array of water equivalent depths (dWE). These rays were
plotted versus isocentric separation and ray-tracing direction. Planar doses were
compared between the isocentric plane in the patient computed tomography and the
water equivalent phantom using gamma criteria of 2%-2 mm and 3%-3 mm. Except in
one lung case, >95% gamma agreement was seen when using 3%-3 mm and >90% pass
rate was seen when using 2%-2 mm. For head and neck cases, gamma-fail was
restricted to the periphery. For mediastinum cases, gamma-fail was restricted to
the lungs. This study demonstrates that a heterogeneous patient can be converted
to a water phantom with comparable dosimetric characteristics and disagreements
restricted to the lung area for both modulated and open beams. Potential sources
of error include the dWE calculation and TPS dose computation.
PMID- 29962688
TI - A Practical Method to Optimize Quality Assurance Results of Arc Therapy Plans in
Beam Modeling.
AB - Dosimetric accuracy of a volumetric modulated arc therapy (VMAT) plan is directly
related to the beam model, particularly with multileaf collimator
characterization. Inappropriate dosimetric leaf gap (DLG) value can lead to a
suboptimal beam model, with significant failure in patient-specific quality
assurance (PSQA) of VMAT plans. This study addressed the systematic issue of beam
modeling and developed a practical method to determine the optimal DLG value for
a beam model. Several complex VMAT plans were selected for the quality assurance
analysis using the variable DLG values. The results of three-dimensional (3D)
Gamma analysis as a function of the DLG at 3%/3 mm, 2%/2 mm, and 1%/1 mm criteria
were fitted by a polynomial curve. The DLG value corresponding to the maximum
Gamma passing rate for each polynomial fitting function was derived, and the
average was calculated to be the optimal DLG value for each model. The 3D Gamma
analysis was repeated with the optimal DLG value to verify the dosimetric
accuracy of each VMAT case by PSQA. Gamma passing rates are seen to vary
considerably with the DLG values and different analysis criteria (3%/3 mm, 2%/2
mm, and 1%/1 mm) for each case. The optimal DLG derived for each model was 1.16
mm and 1.10 mm, much larger than the measured value (about 0.3 mm). The beam
models with the optimal DLG was able to produce an average Gamma passing rate of
97.1% (range, 94.6%- 99.1%) at 3%/3 mm and 93.5% (range, 89.0%- 96.5%) at 2%/2 mm
for one beam model, and 97.1% (range, 94.8%- 99.1%) at 3%/3 mm, and 93.3% (range,
88.8%- 96.7%) at 2%/2 mm for another. The overall accuracy of dose calculation
for VMAT plans should be optimized with a compromise of varied modulation
complexities in a beam model. We have developed a practical method to derive the
optimal DLG value for each beam model based on the Gamma passing criterion. This
technique should be applicable in general for all beam energies and patient
cases.
PMID- 29962689
TI - Patient-Specific Quality Assurance Protocol for Volumetric Modulated Arc Therapy
using Dose Volume Histogram.
AB - A retrospective study was performed to explore the use of dose volume histogram
(DVH) metrics in a patient-specific quality assurance protocol for volumetric
modulated arc therapy (VMAT). Fourteen head and neck (HN) and ten brain patients
treated with VMAT at the Launceston General Hospital were retrospectively
analyzed using the new protocol to identify cases where patient dose errors
exceed the established action levels that were not originally detected by either
point dose and/or gamma index methods. The Sun Nuclear 3DVH software was used to
estimate the dose delivered to the patient volume in terms of DVH dose errors.
Thus, three different pretreatment verification methods were used to assess if a
plan was considered acceptable. In two particular cases, the dose difference
determined with point dose was above the established threshold, although it was
found that this was due to the placement of the chamber in the phantom. In all
cases, 3DVH confirmed that the dose delivered to target volumes (planning target
volume - D50%) and to relevant organs at risk was within prescribed dose
tolerances. This study has demonstrated the integration of DVH metrics into a
VMAT PSQA protocol to provide clinically meaningful results that complement point
dose and gamma index measurements. 3DVH should be regarded as an investigative
tool that may be useful in diagnosing the cause of failed plans since it allows
dose errors to be related to the patient anatomy.
PMID- 29962690
TI - Validation of Delivery Consistency for Intensity-Modulated Radiation Therapy and
Volumetric-Modulated Arc Therapy Plans.
AB - The delivery consistency of a Varian Edge linear accelerator over the entire
course of treatment for nasopharynx carcinoma (NPC) and prostate cancer intensity
modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT)
treatment plans was investigated using four different approaches. Three NPCs and
three prostate plans were delivered in 34 and 29 consecutive days, respectively,
using a Varian Edge equipped with a 120 high-definition (HD) multileaf collimator
(MLC). All deliveries were measured with an electronic portal imaging device
(EPID), and MapCheck2 and ArcCheck commercial systems with gamma analysis used to
compare the results of all daily measurements against the pretreatment patient
specific quality assurance. The daily log files generated were also assessed for
differences between the actual and planned doses using an in-house program to
replace the original values in the DICOM plan files with the delivered parameter
values from the log file, and then exporting the plans back to the treatment
planning system for reconstruction of the actual dose delivered. The trajectory
log file and EPID methods showed very good agreement, with minimal deviations
between the daily delivered and reference doses. However, comparisons of the
MapCheck2 and ArcCheck with the EPID revealed statistically significant
differences (P < 0.001, one-tailed) with greater daily fluctuations, raising
concerns over the performance, and reliability of the MapCheck2 and ArcCheck
systems when being used to identify IMRT and VMAT plans with poor dosimetric
accuracy. We conclude that the Varian Edge linear accelerator equipped with a 120
HD MLC can consistently deliver IMRT and VMAT plans over the entire treatment
course.
PMID- 29962691
TI - Dosimetric, Radiobiological and Secondary Cancer Risk Evaluation in Head-and-Neck
Three-dimensional Conformal Radiation Therapy, Intensity-Modulated Radiation
Therapy, and Volumetric Modulated Arc Therapy: A Phantom Study.
AB - This analysis estimated secondary cancer risks after volumetric modulated arc
therapy (VMAT) and compared those risks to the risks associated with other
modalities of head-and-neck (H&N) radiotherapy. Images of H&N anthropomorphic
phantom were acquired with a computed tomography scanner and exported via digital
imaging and communications in medicine (DICOM) standards to a treatment planning
system. Treatment plans were performed using a VMAT dual-arc technique, a nine
field intensity-modulated radiation therapy (IMRT) technique, and a four-field
three-dimensional conformal therapy (3DCRT) technique. The prescription dose was
66.0 Gy for all three techniques, but to accommodate the range of dosimeter
responses, we delivered a single dose of 6.60 Gy to the isocenter. The lifetime
risk for secondary cancers was estimated according to National Council on
Radiation Protection and Measurements (NCRP) Report 116. VMAT delivered the
lowest maximum doses to esophagus (23 Gy), and normal brain (40 Gy). In
comparison, maximum doses for 3DCRT were 74% and 40%, higher than those for VMAT
for the esophagus, and normal brain, respectively. The normal tissue complication
probability and equivalent uniform dose for the brain (2.1%, 0.9%, 0.8% and 3.8
Gy, 2.6 Gy, 2.3 Gy) and esophagus (4.2%, 0.7%, 0.4% and 3.7 Gy, 2.2 Gy, 1.8 Gy)
were calculated for the 3DCRT, IMRT and VMAT respectively. Fractional esophagus
OAR volumes receiving more than 20 Gy were 3.6% for VMAT, 23.6% for IMRT, and
100% for 3DCRT. The calculations for mean doses, NTCP, EUD and OAR volumes
suggest that the risk of secondary cancer induction after VMAT is lower than
after IMRT and 3DCRT.
PMID- 29962692
TI - Interfraction Dose Variations in Organs at Risk during CT-Based High-Dose-Rate
Brachytherapy in Locally Advanced Carcinoma Cervix: An Early Experience of a
Tertiary Care Center.
AB - Purpose: Dose received by organs at risk (OAR) in high-dose-rate (HDR)
intracavitary brachytherapy (ICBT) for locally advanced cervical cancer impacts
the late toxicity profile of the treatment. In the present study, we analyzed the
inter-fraction variations of the minimum dose received by the most irradiated 2cc
volumes (D2cc) of the OARs in ICBT. Methods and Materials: This prospective study
included 40 patients with cervical cancer stage FIGO IIB-IVA treated with HDR
ICBT and concomitant chemoradiotherapy with Computerized tomography (CT)- based
three-dimensional planning. In addition, for 20 (of the 40) patients, the first
fraction plan was superimposed on the second fraction images for studying its
dosimteric impact on the OAR. The D2cc data for the OAR was statistically
analyzed for interfraction variations with Chi-square test or Fisher exact test
as applicable. Paired t-test was used to compare the difference in means for the
D2cc values between the three fractions. Results: The interfraction variations of
the D2cc values of the OAR were statistically insignificant having P = 0.41, 0.8,
and 0.20 for bladder, rectum, and sigmoid, respectively. Further, in 6 out of 20
cases, wherein first fraction plan was superimposed on second fraction images,
the OAR doses exceeded the prescribed tolerance limits. Conclusion: We did not
find variations in the OAR doses when each fraction was planned and treated
individually. However, we found that if a single plan is used to treat subsequent
fractions, OAR doses may exceed tolerance in about 30% of the cases. We believe
that a larger sample size with improved compliance of bladder and bowel protocols
would be needed to arrive at definitive conclusions.
PMID- 29962693
TI - Documentation of a New Intracavitary Applicator for Transrectal Hyperthermia
Designed for Prostate Cancer Cases: A Phantom Study.
AB - Concerning clinical trials, intracavitary hyperthermia has already shown
antitumor activity and has a potential role in the treatment of prostate cancer.
The aim of this study was to document a new intracavitary applicator operating at
433 MHz, designed for transrectal hyperthermia, as well as to assess the specific
absorption rate (SAR) distributions in terms of temperature measurements in a
soft-tissue phantom. The microwave applicator consists of a dipole-type lambda/2,
a reflector, and the cooling system. The applicator was placed into a soft-tissue
gel-phantom box that was mimicking the dielectric properties of the normal
tissue. A calibrated thermometer was implanted inside the phantom at specific
locations, to calculate temperature distributions. The maximum value of the SAR
was 108 W/kg on the surface's central area at the footprint of the antenna, while
the penetration depth was at around 3 cm. Our experimental measurements confirmed
the role of the reflector concerning the directivity in a certain area and non
icotropic, by means of protecting normal tissues around the prostate. The SAR
experimental measurements showed that our applicator might be used effectively as
a treatment device for prostate cancer, demonstrating a clear advantage over
other similar transrectal devices.
PMID- 29962694
TI - Erratum: Magnetic Resonance Imaging for Adaptive Cobalt Tomotherapy: A Proposal.
AB - [This corrects the article on p. 242 in vol. 31, PMID: 21206640.].
PMID- 29962696
TI - Periodontal disease prevalence: Right time to address the challenges.
PMID- 29962695
TI - Is "Impact" the "Factor" that matters...? (Part II).
PMID- 29962697
TI - Nanotechnology in dentistry: Unleashing the hidden gems.
AB - Nanotechnology in dentistry refers to new generation research carried out to
develop newer technologies, restorative materials and drugs of Nano dimensions.
The word "Nano" refers to Nanoscale particles. Although the science of
nanotechnology in dentistry is recent and less developed, but still has vast
potential to show advancement and improvement in the field of dentistry. As
nanotechnology is making firm grip in other fields such as drug delivery system
and reducing toxicity by the emergence of more biocompatible materials.
Clinicians, researchers, and manufacturers are taking keen interest and
participation in the advancement of this field. This paper is an attempt in
unleashing the hidden gems of nanotechnology-focusing latest developments in
field restorative and surgical dentistry to enhance the quality and
biocompatibility of newer generation dental materials and technology. This paper
will also focus on potential hurdles encountered in the development of newer
materials by utilizing the science of nanotechnology and their potential safety
issues concern.
PMID- 29962699
TI - Correlation between interleukin-1beta and matrix metalloproteinase-1 levels in
crevicular fluid with a proposed periodontal disease index in children.
AB - Background: The crevicular fluid contains biomarkers that allow the
identification of periodontal disease, anticipation of its risk, and prediction
of its progression. Purpose: The purpose of this study is to correlate
interleukin-1beta (IL-1beta) and matrix metalloproteinase-1 (MMP-1) levels in
crevicular fluid with periodontal disease severity in schoolchildren. Methods: A
cross-sectional study was conducted in 82 schoolchildren between 9 and 12 years.
The biofilm percentage, attachment level, gingival recession, dental calculus,
and bleeding on probing were measured in the teeth 16, 26, 36, 41, and 46. These
five parameters obtained were considered to propose a disease score between 0 and
10 points. In crevicular fluid from the tooth with the highest score, IL-1beta
and MMP-1 levels were measured. Results: According to the proposed score, mild
gingivitis was identified in 20 schoolchildren, moderate gingivitis in 30, and
severe gingivitis in 32. Biofilm percentage, IL-1beta, and MMP-1 levels increased
as the severity of the disease increase. The mean and 95% confidence interval
were 23.2 pg/MUl (18.6-27.7), 37.3 pg/MUl (27.8-46.9), and 44.6 pg/MUl (34.4
58.8) (P = 0.01) for IL-1beta and 2.69 mol/min (2.51-2.87), 4.43 mol/min (3.9
4.95), and 5.59 mol/min (4.81-6.38) (P < 0.001) for MMP-1 in each group,
respectively. The proposed clinical score correlated with biofilm percentage (r =
0.63), IL-1beta (r = 0.50), and MMP-1 (0.45) levels, P < 0.001 in all cases.
Conclusions: The proposed clinical score for periodontal disease in children
correlated with percentage of biofilm, IL-1beta, and MMP-1 levels.
PMID- 29962698
TI - Serotypes of Aggregatibacter actinomycetemcomitans in relation to periodontal
status and assessment of leukotoxin in periodontal disease: A clinico
microbiological study.
AB - Context: Aggregatibacter actinomycetemcomitans (A.a) serotypes may add some
important information of the pathogenetic background of periodontal infections.
A.a leukotoxin is an important virulence factor in the pathogenesis of
periodontal disease and its rate of progression. When compared to minimally
leukotoxic strains, variants of A.a highly leukotoxic strains produce 10-20 times
more leukotoxin. Aims: The aim of the present study was to detect serotypes a, b,
c, d, and e of A.a its leukotoxin and find its correlation with periodontal
status. Settings and Design: Microbiological analysis and cross-sectional study.
Materials and Methods: A total of 80 subjects (40 chronic periodontitis and 40
aggressive periodontitis) in the age range of 14-55 years were selected.
Subgingival plaque samples were collected and checked for the presence of A.a.
Following isolation of the organism, detection of the serotypes and leukotoxin
assessment was done. Statistical Analysis Used: The proportions of A.a were
calculated using descriptive statistics in terms of percentage. Chi-square test
was used to find association between serotype, leukotoxin, and periodontal
disease in individual group. Results: Out of 80 plaque samples, 45% tested
positive for A.a. serotype b was detected in 33.33%, whereas serotype e in 8.33%
samples and serotype c in 2.77% samples. Serotypes a and d were not detected in
any of the samples. A combination of serotypes was seen in 47.22% of the sites.
Of these 76.47% showed a combination of 2 serotypes, while 23.52%showed a
combination of 3 serotypes. 8.33% showed untypable serotype. All samples had low
toxic variants of A.a. Conclusions: Serotype b and serotype e were predominant in
chronic periodontitis, and serotype b was predominant in aggressive
periodontitis. An association could be present between serotype and periodontal
disease.
PMID- 29962700
TI - Association between obstructive sleep apnea and comorbidities with periodontal
disease in adults.
AB - Background: Several studies have reported an association between periodontal
disease and obstructive sleep apnea (OSA). However, heterogeneity of results
suggests that there is insufficient evidence to support this association. Aims:
The objective of this study was to identify the association between periodontal
disease and OSA in adults with different comorbidities. Settings and Design: One
hundred and ninety-nine individuals (107 women and 92 men) underwent
polysomnography with a mean age of 49.9 years were recruited. Materials and
Methods: The presence of OSA, comorbidities, and periodontal disease was
evaluated in each individual. Student's t-tests or Chi-square and ANOVA tests
were used to determine the differences between groups. Results: The prevalence of
periodontal disease was 62.3% and 34.1% for gingivitis. The results showed no
statistically significant association between all groups of patients with OSA and
non-OSA patients for gingivitis (P = 0.27) and for periodontitis (P = 0.312).
However, statistically significant association was shown between periodontitis
and mild OSA compared with the periodontitis and non-OSA referent (P = 0.041;
odds ratio: 1.37 and 95% confidence interval 1.11-2.68). The analysis between OSA
and comorbidities showed a statistically significant difference for patients with
OSA and hypertension (P < 0.001) and for patients with OSA and hypertensive
cardiomyopathy (P < 0.001) compared with healthy individuals. Periodontitis was
more likely in men with severe OSA and with any of two comorbidities such as
hypertension or hypertensive cardiomyopathy. Women with hypertension or
hypertensive cardiomyopathy were more likely to have mild OSA, and these
associations were statistically significant (P < 0.05). Conclusions: This study
identified association between periodontitis and mild OSA and this association
was more frequent in women with hypertension or hypertensive cardiomyopathy.
Periodontitis was associated with severe OSA in men who showed any of two
comorbidities such as hypertension or hypertensive cardiomyopathy.
PMID- 29962701
TI - Indocyanine green-mediated photothermal therapy in treatment of chronic
periodontitis: A clinico-microbiological study.
AB - Background: Photodynamic therapy (PDT) has developed as an alternative treatment
modality in periodontitis patients. Different photosensitizers used over the
years have shown contradictory results. Thus, recently indocyanine green (ICG)
mediated photothermal therapy has emerged for the treatment of chronic
periodontitis. Aim: The present study aimed at comparing and evaluating the
effects of photothermal therapy using ICG in the treatment of chronic
periodontitis with scaling and root planing (SRP). Materials and Methods: This
was a randomized, controlled, clinical trial where fifty participants were
equally divided into two groups, i.e., control group (SRP) and test group (SRP +
photothermal therapy). Clinical parameters were evaluated at baseline and 6-month
follow-up. These were plaque index (PI), bleeding on probing (BOP), probing depth
(PD), and clinical attachment level (CAL). Microbiological analysis of plaque
sample was also done to check for anaerobic mixed flora. Results: Significant
reduction was seen in PD, CAL, and BOP in the test group as compared to control
group after 6 months (P < 0.05). However, intergroup comparison of PI showed
nonsignificant results (P > 0.05). Anaerobic culture of plaque samples of test
group also revealed a significant reduction of microorganisms in comparison with
control group. Conclusion: ICG-mediated photothermal therapy can act as an
alternative to antimicrobial PDT as an adjunct to SRP in the treatment of chronic
periodontitis.
PMID- 29962702
TI - Comparative evaluation of efficacy and soft tissue wound healing using diode
laser (810 nm) versus conventional scalpel technique for second-stage implant
surgery.
AB - Background: This study was aimed to compare the efficacy and soft tissue wound
healing using diode lasers (810 nm) versus conventional scalpel approach as
uncovering technique during the second-stage surgery in implants. This was a
prospective, randomized study which was conducted on 20 subjects in which the
implants were already placed using a two-stage technique. Implant sites were
examined and the patients were randomly divided into two groups. Materials and
Methods: Patients were randomly divided into two groups, i.e., Group A and Group
B. In Group A, implants were uncovered as a part of Stage II surgery with
conventional scalpel technique, and in Group B, implants were uncovered using 810
nm diode laser. Clinical parameters such as need and amount of local anesthesia,
duration of surgery, intraoperative bleeding, pain index, wound healing index
(HI), and time for impression taking were recorded at various intervals. Results:
Statistical differences for clinical parameters were seen between Group A and
Group B showing uncovery of implant with laser more effective, and for time of
impression taking, difference was statistically significant showing that
impressions were taken early in case of Group A because of better healing which
was recorded with help of HI, but the difference in time of healing between Group
A and Group B was not statistically significant. Conclusion: The use of a diode
laser (810 nm) in the second-stage implant surgery can minimize surgical trauma,
reduce the amount of anesthesia, improve visibility during surgery due to the
absence of bleeding, and eliminate postoperative discomfort.
PMID- 29962703
TI - Regenerative potential of autologous platelet-rich fibrin with and without amnion
membrane in the treatment of Grade-II furcation defects: A clinicoradiographic
study.
AB - Context: Platelet-rich fibrin (PRF), platelet concentrate composed of cytokines
and structural glycoproteins trapped within polymerized fibrin meshwork, has the
potential to accelerate healing of periodontal tissues. Amnion membrane has also
attracted a lot of attention in periodontal regeneration due to the presence of
variety of growth factors. Aims: The aim of the study is to evaluate and compare
the regenerative potential of autologous PRF with and without amnion membrane in
the treatment of Grade II furcation defects. Settings and Design: This was a
double-masked randomized, split-mouth design study. Materials and Methods:
Fifteen patients with thirty mandibular degree II furcation defects were randomly
allotted into Group I (PRF and amnion membrane) and Group II (PRF). Clinical
parameters such as plaque index and gingival index-at defect site along with
probing pocket depth, and relative attachment level and furcation defect depth
were recorded at baseline, 3 months, and 6 months postoperatively. Assessment of
radiographic parameters was done at baseline and 6 months postoperatively aided
by computer-assisted tomography (Dentascan). Statistical Analysis Used: For
intragroup variations, Wilcoxon signed-rank test, and for comparison between the
two groups/intergroup variations, Independent t-test and Mann-Whitney test was
performed. Results: All clinical and radiographic parameters showed statistically
significant improvement at the sites treated with PRF and amnion membrane
compared to those with PRF alone. Conclusions: Within the limitation of this
study, there was greater pocket reduction, attachment level gain, and bone fill
at sites treated with PRF and amnion membrane as compared to PRF alone.
PMID- 29962704
TI - Comparative evaluation of hemodynamic, vasoconstrictive, and SpO2 variability
during different stages of periodontal surgery performed using 0.5% ropivacaine
or 2% lignocaine HCl (1:80,000 adrenaline) local anesthesia: A randomized, double
blind, split-mouth pilot study.
AB - Aim: The aim of this study is to compare anesthetic, hemodynamic,
vasoconstrictive, and SpO2 variability of 0.5% ropivacaine to the "gold standard"
lignocaine (2%) with epinephrine (1:80,000) during periodontal surgery. Materials
and Methods: A total of 20 systemically healthy controls meeting the inclusion
criteria were selected from the Outpatient Department of Sri Sai College of
Dental Surgery. Preoperatively, all participants were infiltrated with 0.5 ml of
0.5% ropivacaine intradermally as test solution to record any allergic reaction.
Open flap debridement was performed using local anesthesia containing 2%
lignocaine hydrochloride with 1:80,000 epinephrine or 0.5% ropivacaine.
Recordings were made of the time of onset, duration of action, the intensity, and
depth of anesthesia and various hemodynamic changes throughout the surgical
procedure. In addition, blood loss volume and postoperative pain were also
assessed. Results: Ropivacaine showed statistically longer duration of action
(mean+/-SD =5.3+/-0.71 hrs) than lignocaine with epinephrine (mean=2.14+/-0.98
hrs). Blood loss during flap surgery was comparatively less when performed under
ropivacaine. No statistical differences were observed in systolic BP, diastolic
BP, SpO2 and heart rate during different stages of periodontal surgery between
either of the local anesthetic agents. Conclusion: Ropivacaine demonstrates
comparable efficacy as lignocaine with added advantage of longer duration of
action and superior postoperative pain control. No adverse events from this newer
anesthetic were noted, and hence, it can be used safely as a viable local
anesthetic for periodontal surgical procedures.
PMID- 29962705
TI - Soft-tissue esthetic outcome of single implants: Immediate placement in fresh
extraction sockets versus conventional placement in healed sockets.
AB - Background: Immediate implant placement has advantages such as requiring fewer
surgical procedures and decreased treatment time; however, unpredictable soft-
and hard-tissue outcome is a problem. This study aimed to compare the soft-tissue
esthetic outcome of single implants placed in fresh extraction sockets versus
those placed in healed sockets. Materials and Methods: This cross-sectional,
retrospective study was performed on 42 patients who received single implants.
Twenty-two patients with a mean age of 40.14 years received immediate implants
while 18 patients with a mean age of 43.40 years were subjected to conventional
(delayed) implant placement. The mean follow-up time was 14.42 +/- 8.37 months
and 18.25 +/- 7.10 months in the immediate and conventional groups, respectively.
Outcome assessments included clinical and radiographic examinations. The esthetic
outcome was objectively rated using the pink esthetic score (PES). Results: All
implants fulfilled the success criteria. The mean PES was 8.54 +/- 1.26 and 8.10
+/- 1.65 in the immediate and conventional groups, respectively. This difference
was not statistically significant (P = 0.329). The two PES parameters, namely,
the facial mucosa curvature and facial mucosa level had the highest percentage of
complete score. Conclusions: Immediate and conventional single implant treatments
yielded comparable esthetic outcomes.
PMID- 29962706
TI - Indications for palatal sinus lift: Case series.
AB - Background: Open sinus lift is indicated in posterior maxilla when subantral bone
is insufficient for insertion of dental implants. Lateral approach is the most
used technique. Sometimes, this surgery is difficult due to thick buccal bone or
other anatomic variations of maxillary sinus. Aim: The aim of this study was to
determine cases that palatal approach open sinus lift is indicated. Settings and
Design: This study was a retrospective study. Materials and Methods: Archive
files of Dental Implant Department of Mashhad Dental School were searched for
palatal sinus lift. The reason for patients was noticed. Pre- and post-operative
radiographs were evaluated. Results: Ten patients with palatal approach sinus
lift were included. Seven patients had previous insufficient sinus lift, one
patient had acute palatonasal recess, and two other patients had thick buccal
bone. Conclusion: Palatal approach is maxillary open sinus lift is a useful
auxiliary in patients with heavy buccal vestibule scar, thick buccal bone, deep
palatonasal recess, and for reentry augmentation.
PMID- 29962707
TI - Prevalence of variations in morphology and attachment of maxillary labial frenum
in various skeletal patterns - A cross-sectional study.
AB - Background: Maxillary labial frenum is a dynamic structure with a diverse
morphology. Although an abnormal labial frenum is associated with syndromic and
nonsyndromic conditions, it is often been neglected during the routine intraoral
examination. The significance of various types of frenum (normal to abnormal),
based on the attachment site and morphology in different skeletal patterns, has
not been studied yet. Materials and Methods: A cross-sectional study was
conducted in a clinical setting on 150 participants (50 each in Class I, Class
II, and Class III skeletal pattern) within the age group of 13-30 years. Frenum
was examined by direct visual method and intraoral photographs were taken for all
the participants. Results: Chi-square and Fisher's exact tests were used. No
gender-wise differences were found among the various frenum typologies. Mucosal
type was the most prevalent in Class I and II and gingival type in Class III.
Simple frenum was the common type in all the three groups. However, abnormal
frenum categories based on its location and morphology were more in class III and
found to be statistically significant. Papillary and papillary penetrating types
are significantly associated with skeletal class III pattern and midline diastema
(P < 0.05). Conclusion: The prevalence of papillary and papillary penetrating
types of frenum are significantly more in Class III skeletal pattern. A labial
frenum that is attached close to the gingival margin could be an etiological
factor in midline diastema, mucogingival problems, and affect the growth of the
alveolar process. Hence, an early diagnosis of abnormal frenum prevents the
emergence of periodontal as well as orthodontic problems.
PMID- 29962708
TI - Grinspan syndrome with periodontitis: Coincidence or correlation?
AB - Grinspan syndrome is a syndromic complex which comprises a triad of hypertension,
diabetes, and oral lichen planus. It remains an enigmatic condition that whether
it is separate entity or drug-induced lichenoid reaction emerging due to
medications used to treat hypertension and diabetes. Diabetes is related to long
term hyperglycinemia leading to accelerated destruction of both nonmineralized
connective tissue and bone leading to periodontitis. Moreover, there is also a
possible link between cardiovascular disease and periodontitis. Here, we are
presenting a case with the symptomatic triad fulfilling the diagnostic criteria
of Grinspan syndrome. A 50-year-old female with type 2 diabetes mellitus and
vascular hypertension came with the chief complaint of bleeding gums and severe
burning sensation of the oral cavity. In addition, she was having generalized
alveolar bone loss and clinical attachment loss. To the best of our knowledge,
this coexistence has not been reported earlier. This needs further evaluation so
that the preventive measures can be taken at early stage.
PMID- 29962709
TI - Shield the socket: Procedure, case report and classification.
AB - The extraction of a tooth leads to a cascade of events which results in
resorption of the alveolar bone around the socket. The buccal bone loss that
occurs postextraction leads to vertical and horizontal bone loss. It requires
complex hard and soft-tissue reconstruction to achieve esthetically pleasing
results in such cases. In the socket-shield technique (SST) the root is bisected,
and the buccal two-third of the root is preserved in the socket so that the
periodontium along with the bundle bone and the buccal bone remains intact. A
classification of SST technique is proposed depending on the position of the
shield in the socket. This classification is required so as to help in
understanding the preparation design and the role of shield and in maximizing the
usage of the shield to achieve best possible esthetics in immediate implant
placement sites.
PMID- 29962710
TI - Coronally advanced flap in conjunction with platelet-rich fibrin-assisted
immediate management of residual gingival defect following surgical excision of
recurrent pyogenic granuloma in the maxillary esthetic segment.
AB - Exophytic gingival lesions are more frequently encountered intraorally, out of
which few are reactive in nature. Pyogenic granuloma (PG) is one of the commonly
occurring reactive benign mucocutaneous lesions; exact etiopathogenesis remains
unclear. Although surgical excision is the treatment of choice, sometimes it may
induce residual soft defect formation which further creates an esthetic problem,
root sensitivity, etc., The present case report not only describes the diagnosis
and treatment of PG but also the immediate successful management of residual
gingival defect in the esthetic area (which was originated as a sequel of the
excisional biopsy of recurrent PG) by utilizing platelet-rich fibrin in
conjunction with coronally advanced flap in single-stage surgery. Clinical
healing was uneventful and satisfactory at 2 weeks, and excellent coverage of
residual mucogingival defect with gingival esthetic and normal sulcus depth was
observed at 3 and 6 months postoperatively without any sign of a complication.
PMID- 29962711
TI - Ascertaining the regenerative potential of the "gold standard" grafts: Achieving
100% root coverage in Miller's Class III recession with periosteal pedicle graft
and autogenous bone.
AB - Recession of the gingiva is defined as the stripping of a portion of the dental
root surface as a result of gingival margin shifting apically. Various techniques
have been advocated for root coverage. The practice of utilizing periosteal
pedicle graft for covering gingival recession defects is a contemporary
development. Utilizing bone grafts for hard tissue regeneration has also been
implemented. This case report assesses the effectiveness of the surgical approach
utilizing autogenous bone and periosteum for recession coverage. A participant
with Miller's Class III gingival recession in #23 and #24 was treated using this
technique. The loss of periodontal attachment was recorded to be 8 mm and 5 mm on
the mid-buccal surface of the upper left canine and first premolar, respectively.
Clinical parameters were recorded at 1, 3, 6, 9, and 12 months postoperatively.
Complete root coverage was achieved when evaluated from baseline till 12 months,
with clinical attachment level and keratinized tissue gain. The results of
esthetics in terms of color match and tissue contours were satisfactory to the
patient as well as to the clinicians.
PMID- 29962712
TI - F-18 FDG PET-CT Versus Contrast Enhanced CT in Detection of Extra Nodal
Involvement in Patients with Lymphoma.
AB - Aim and Objectives: The aim of this study is to assess the added value of hybrid
fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
(PET/CT) in the evaluation of extranodal involvement in patients with lymphoma in
comparison to contrast-enhanced CT (CECT). Patients and Methods: All patients had
lymphoma, proved by histopathological and immunophenotyping examinations. They
underwent CECT and F-18 FDG PET-CT studies. Both CECT and PET/CT studies were
done within 30 days. Results: The study included 144 patients 92 (63.9%) males
and 52 (36.1%) females with mean age 49.3 years (range 18-80 years). A total of
102 (70.8%) patients had non-Hodgkin lymphoma and 42 patients (18.1%) had Hodgkin
disease, diffuse large B-cell lymphoma subtype had the highest prevalence 52.8%
(76/144), whereas lymphocytic predominance was the least prevalent 1.4% (2/144)
followed by mucosa-associated lymphoid tissue lymphoma 2.8% (4/144) and small
lymphocytic type 4.2% (6/144), mixed cellularity (MC), T-cell, and follicular
type were equally distributed 6.9% (10/144 each). The lung was the most common
site as it was involved in 34 patients followed by bone and bone marrow 32
patients, spleen 18, liver 16, nasopharynx 8, stomach 6, cutaneous and
subcutaneous tissue 6, peritoneum, cecum, small intestine, brain, and
intramuscular four patients each. However, the parotid and pancreas were the
least common sites two patients each. The overall sensitivity, specificity PPV,
NPV, and accuracy of PET/CT and CECT are 97%, 20% 94.2%, 33.3% and 91.7% and
89.6%, 60%, 96.8%, 30% and 87.5%, respectively. Conclusion: F-18 FDG-PET/CT can
accurately monitor the extranodal lymphoma, it can detect metabolically-active
lesions without CT structural changes and identify viable tumor in normal size
lymph nodes. FDG-PET/CT is more effective than CECT in evaluating extra nodal
lymphomatous infiltration, especially in the spleen, bone, and bone marrow.
PMID- 29962713
TI - Role of 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography
Scan in Primary Staging of Breast Cancer Compared to Conventional Staging.
AB - Aim: In newly diagnosed carcinoma breast cancer patients, comparing conventional
staging and 18F-fluorodeoxyglucose positron-emission tomography-computed
tomography (18F-FDG PET/CT) staging. Materials and Methods: This was a
retrospective observational study. A total of 171 new diagnosed carcinoma breast
patients who underwent staging 18F-FDG PET/CT scan and routine conventional
imaging including mammosonography of breast and axilla, chest X-ray, ultrasound
sonography abdomen, and bone scan were included in the study. Staging was done
according to the American Joint Committee on Cancer staging (tumor-node
metastasis). Changes in staging and management with 18F-FDG PET/CT scan were
assessed. Results: Overall PET/CT upstaged in 22.2% of cases and changed
management in 15.78% of cases. PET/CT upstaged in three of eight cases in Stage
IA patients but changed management in only one case. In Stage IIA, of 31 patients
PET/CT upstaged in two patients (6.45%). In Stage IIB, of 45 patients PET/CT
upstaged in six patients (13.3%). In Stage IIIA, of 22 patients PET/CT upstaged
in six patients (27.2) and in five patients there is a change in management. In
Stage IIIB, of 43 patients PET/CT upstaged in 21 patients (48.8%) with change in
management in 13 patients (25.5%). Conclusion: 18F-FDG PET/CT scan can be helpful
in a significant number of patients with Stage IIB and above in upstaging and
changing management.
PMID- 29962714
TI - Comparative Study of Positron Emission Tomography/Computed Tomography and
Computed Tomography in the Evaluation of Post-treatment Carcinoma Cervix
Patients.
AB - Purpose of Study: To evaluate and compare imaging findings using computed
tomography (CT) alone and positron emission tomography/CT (PET/CT) fusion imaging
in posttreatment carcinoma cervix patients for recurrence. Subjects and Methods:
From June 2014 to May 2016, 50 posttreatment carcinoma cervix patients were
referred to our institution for PET/CT imaging. In all 50 of these patients
referred for evaluation, a reliable reference standard was available. The
reference standard was established by histopathological examination of accessible
locoregional and nodal/distant metastatic involvement or follow-up of patients.
CT and PET/CT were performed and analyzed for locoregional, pelvic nodal, and
distant metastasis involvement in posttreatment carcinoma cervix cases. Results:
In the evaluation of locoregional involvement, CT alone was found to have a
sensitivity of 75% and specificity of 90% while PET/CT was found to have a
sensitivity of 95% and specificity of 100%. Furthermore, in evaluation of pelvic
nodal involvement, CT alone was found to have a sensitivity of 72% and
specificity of 92.6% while PET/CT was found to have a sensitivity of 95.5% and
specificity of 92.9%. In context to distant metastasis involvement (including
para-aortic nodes), CT alone was found to have a sensitivity of 91.7% and
specificity of 96.2% while PET/CT was found to have a sensitivity of 95.8% and
specificity of 100%. PET/CT fusion in comparison to CT alone is better in
sensitivity and specificity in the detection of locoregional involvement, pelvic
node invasion, and distant metastasis in posttreatment carcinoma cervix cases.
PMID- 29962716
TI - Radiation Exposure to the Personnel Performing Robotic Arm-Assisted Positron
Emission Tomography/Computed Tomography-Guided Biopsies.
AB - Purpose: The aim of the study was to estimate the radiation burden to personnel
performing robotic arm-assisted positron emission tomography/computed tomography
(PET/CT)-guided metabolic biopsies and to staff assisting the procedure in a
PET/CT facility. Materials and Methods: We estimated the whole-body exposures to
physicians and staff based on the dose rate measurement with an ionization
chamber-based calibrated survey monitor and pocket dosimeters during the robotic
arm-assisted 2-[F-18]-fluoro-2-deoxy-D-glucose PET/CT-guided biopsies from
September 2016 to February 2017. In addition, we also noted the time to biopsy
after injection and total biopsy time during which the staff was exposed to the
radiation. Results: In this prospective study, PET/CT-guided biopsy was performed
in 50 patients (males - 36, females - 14) with a mean age of 54 +/- 15 years
(range17-78 years). Of the 50 biopsy procedures, 18 were lung biopsies, 10 were
bone biopsies, and 22 biopsies were from abdomen/pelvic lesions. The mean time
taken for the procedure was 26 +/- 11 min. The mean time elapsed between
injection and procedure was 182 +/- 85 min and mean injected activity of 138.38
+/- 74 MBq. The mean whole-body exposure per procedure to an interventionist and
an assistant was 1.88 +/- 0.82 MUSv and 1.04 +/- 0.75 MUSv, respectively. The
mean exposure rates at 0-m and 1-m distance from the patient were 30.77 +/- 14.61
MUSv/h and 2.59 +/- 1.49 MUSv/h, respectively. Conclusion: We conclude that the
interventionist received the highest mean effective dose as compared to the
helping staffs. The occupational radiation exposure was found to be within the
limits as specified by the regulatory authorities (International Commission on
Radiological Protection-103), and PET/CT-guided biopsies were safe from radiation
protection point of view.
PMID- 29962715
TI - Can Early Dynamic Positron Emission Tomography/Computed Tomography Obviate the
Need for Postdiuresis Image in 68Ga-PSMA-HBED-CC Scan for Evaluation of Prostate
Adenocarcinoma?
AB - Introduction: Forced diuresis technique is often adopted to wash out the high
amount of urinary radioactivity that masks the foci of abnormal uptake in the
pelvic region on 68Ga-PSMA-HBED-CC positron emission tomography/computed
tomography (PET/CT) scan in prostate cancer (PC) patients. However, this method
is time-consuming, makes the patient non/less compliant, and is not feasible in
patients with renal dysfunction. We hypothesized that early dynamic imaging can
obviate the need for a postdiuresis view as the urinary activity is expected to
be low at the time. Materials and Methods: A total of 20 biopsy-proven PC
patients who were referred to our department for a 68Ga-PSMA PET/CT for
staging/restaging were prospectively studied. Dynamic PET/CT was done with on
table intravenous (i.v.) injection of 2-3 mCi (74-111 MBq) of the radiotracer.
Dynamic images were acquired over the pelvis with a frame time of 1 min for 10
min. Static images of 2 min/bed position were acquired between 45 and 60 min p.i.
The patients were then administered i.v. furosemide and encouraged water intake
and frequent urination. A static view of pelvic region was acquired at 5 min/bed
at 120 min p.i. A three-dimensional volume of interest (3D-VOI) was plotted on
the primary lesion, bladder, involved nodes if any, pelvic bones at involved and
uninvolved sites, gluteal muscles, and artery. The sentence seems fine. This was
to generate the Time activity curve for analysis. Results: Nine patients were
referred for staging and 11 for restaging. Mean age of 20 patients was 64.6
years, and median prostate-specific antigen level was 21.4 ng/ml (range: 0.05
2180). Prostatic lesion was present in 20 patients, nodal involvement in 8, and
bone involvement in 10 patients. Median maximum standardized uptake value
(SUVmax) of the prostatic lesion (P) showed an ascending trend: 5.31 at 5 min,
10.65 at 60 min, and 10.52 at 120 min p.i. At the same time, median SUVmax of the
bladder (B) also progressed steeply and then decreased postdiuresis: 1.01 at 5
min, 24.6 at 60 min, and 6.88 at 120 min. Despite forced diuresis, the bladder
activity remained higher than that during early dynamic imaging. Median prostate
to-bladder (P/B) ratio was highest during early dynamic imaging at 5 min p.i. was
5.17, while at 60 min, P/B ratio was 0.42 (P = 0.002) and, at 120 min, it was
1.27 (P = 0.009). Further, all the nodal and bone lesions were clearly visualized
on early dynamic images. Conclusion: The study results suggest that early dynamic
imaging performs better than a postdiuresis view in terms of delineation of
prostatic and regional lesions on 68Ga-PSMA scan. Further, it saves time and the
patients are more compliant to this technique.
PMID- 29962717
TI - Dacryoscintigraphy: A Pictorial Essay.
AB - Dacryoscintigraphy is a noninvasive, simple, easy to perform imaging modality
used in the evaluation of epiphora. However, it is an infrequently done study in
nuclear medicine departments. A standardized protocol and a systematic
interpretation of the scans help in answering the queries of the clinicians in
cases of epiphora. We have attempted to build a pictorial essay of the various
findings detected on dacryoscintigraphy.
PMID- 29962718
TI - Thyroglobulin "Nonsecretor" Metastatic Poorly Differentiated Thyroid Carcinoma
with Noniodine Concentrating Disease and Aggressive Clinical Course: A Clinical
Case Series.
AB - Poorly differentiated thyroid carcinomas (PDTC) are a subgroup of thyroid cancers
with aggressive behavior and worse prognosis compared to the well DTC. Limited
diagnostic tools and therapeutic options exist for such cases, and the
appropriate management algorithm continues to evolve in this subgroup. They pose
difficulty in clinical management due to their behavioral heterogeneity and
increased occurrence of aggressive clinical behavior underlining the need for
management individualization. In the present communication, a case series of
three clinically challenging cases of PDTC (with low serum thyroglobulin (Tg) and
iodine nonavidity) are presented with a discourse on their management intrigues,
unresolved issues and the requirement of a distinctive management protocol. A
small fraction of PDTCs may show low serum Tg values, with the questionable
significance of its role for the assessment and monitoring of disease burden in
this group of patients. Given uncommon occurrence, limited and variable
literature data, management guidelines for "nonsecretor" PDTC needs to be more
clearly defined based on scientific evidence. The present clinical case series of
PDTC with low serum thyroglobulin in the context of noniodine concentrating
metastatic disease and aggressive clinical course ("nonsecretor" status) was
noteworthy from this viewpoint.
PMID- 29962719
TI - Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Scan in Castleman's Disease.
AB - Castleman's disease (CD) is a rare benign lymphoproliferative disorder. We are
presenting three cases of CD of which one is unicentric CD, and the other two are
an idiopathic multicentric CD. One of the two multicentric cases is associated
with POEMS syndrome. The whole body 18F-Fluorodeoxyglucose positron-emission
tomography-computed tomography scan plays a significant role in identifying the
centricity, distribution of disease, response to therapy, and in early detection
of remission.
PMID- 29962720
TI - Rare Involvement of Thyroid Cartilage and Thyroid Gland by Multiple Myeloma on
18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.
AB - Multiple myeloma commonly involves the skeleton. Extraosseous disease is
sometimes noticed involving various organs. We present a very unusual site of
myeloma involvement in the thyroid gland and thyroid cartilage.
PMID- 29962721
TI - Silicone Implant Incompatibility Syndrome: Mimicking Metastases on Fluoro-Deoxy
Glucose Positron Emission Tomography-Computed Tomography in a Treated Case of
Carcinoma Breast.
AB - Silicone implant incompatibility syndrome (SIIS) has been identified as a cause
of systemic symptoms such as lymphadenopathy, myalgia, and dyspnea in patients
with silicone implants. We present a case of 76-year-old female patient, treated
for carcinoma left breast with mastectomy and silicone breast implant,
chemotherapy, and radiotherapy 42 years ago. There was a history of implant
rupture and removal 2 years ago. The patient presented with right axillary
swelling and dyspnea. 18-fluorine fluoro-deoxy-glucose positron emission
tomography/computed tomography (F-18 FDG PET-CT) showed mildly FDG-avid left
anterior chest wall and right rectus abdominis deposits, multiple lymph nodes,
and low-grade FDG-avid pneumonitis changes in both lungs. Biopsy from the chest
wall and rectus abdominis deposit was negative for malignancy and revealed foamy
histiocytes and foreign-body giant cell reaction, indicative of SIIS. SIIS is a
mimic for metastases and should be considered as a differential diagnosis in FDG
PET-CT interpretation in patients with silicone breast implant.
PMID- 29962722
TI - Breast Cancer Recurrence Presenting as Solitary Intraparotid Nodal Metastasis
Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography: A Very Unusual
Occurrence.
AB - Primary malignancies of the salivary gland itself are uncommon, while secondary
metastatic deposits are further very rare with description of only few case
reports in the literature. The most common site of metastatic deposit to parotid
gland is from squamous cell malignancies of head and neck, while secondary
deposits from primary in infraclavicular location are very rarely described. We
herein describe the case of an elderly lady who while on adjuvant endocrine
therapy developed metastatic disease with right intraparotid node as the sole
site of metastasis detected on FDG PET scan. This type of presentation of
recurrence is very uncommon, especially in hormonal receptor-positive cases, with
<30 cases described in the literature to the best of our knowledge. This patient
underwent metastasectomy followed by palliative the second-line hormonal therapy
and achieved long-term survival more than usually seen with other metastatic
breast cancers highlighting the importance of metastasectomy in metastatic breast
cancer patients on hormonal therapy who develop metachronous oligometastatic
disease.
PMID- 29962723
TI - A Rare Case of Thyrolipomatosis Presenting with Latent Hyperthyroidism.
AB - Goiter and hyperthyroidism are fairly common problems in the Indian population.
We present a 49-year-old female who presented with thyroid swelling and
suppressed thyroid-stimulating hormone. On evaluation, she was having latent
hyperthyroidism with diffuse and soft thyroid swelling. During the evaluation for
feasibility of radioiodine ablation, she was found to have thyrolipomatosis on
computed tomography. She was counseled for total thyroidectomy and subsequently
underwent the same with histopathology confirming the presence of fatty
infiltration into the thyroid stroma.
PMID- 29962724
TI - Fluorodeoxyglucose-positive Splenic Infarctions are Completely Regressive Just
after 4 Months.
AB - A 55-year-old woman with newly diagnosed hepatocellular carcinoma (HCC) was
hospitalized in our department for the evaluation of selective internal
radiotherapy (SIRT), which consists of an angiography, an intra-arterial
technetium (Tc)-99m-macroaggregated albumin application and Tc-99m sulfur colloid
scintigraphy to assess liver function. Besides the modest intratumoral tracer
accumulation, F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed
tomography (PET/CT) imaging showed two intense focal cuneiform splenic FDG
accumulations which turned out to be splenic infarctions. Four months later, both
hypermetabolic foci were completely regressive in the first follow-up PET/CT
after SIRT. This is the first report of a complete metabolic regression of
splenic infarctions within just 4 months, whereas regression on CT is commonly
seen after more than 2 years.
PMID- 29962725
TI - Multifarious Ga-68 Labeled PET Radiopharmaceuticals in Imaging Various
Malignancies.
AB - The gamut of gallium labeled radiopharmaceuticals contributes to augmented
variety in molecular imaging approach for in vivo identification of tumor
characteristics. The spectrum ranges from somatostatin receptor based target
specific imaging agents, to those used for tumor imaging based on specific
receptor types extending into ones used for therapeutic monitoring. The
versatility of gallium chemistry provides the needed advantage for imaging which
is further exploited in clinical practice influences the specificity of tumor
imaging. Ga-68 has revealed applicability in labeling compounds from
nanoparticles to micro as well as macromolecules. We in this image, present
variety of frequently and infrequently used gallium labeled radiopharmaceuticals,
for imaging diverse malignancies other than conventional established tracers.
PMID- 29962726
TI - Umbilical Varices: A Potential Pitfall in Gastrointestinal Bleed Scintigraphy
Interpretation.
AB - Tc-99m labeled red blood cell (RBC) scintigraphy is commonly used in the
evaluation of acute gastrointestinal (GI) bleeding. On Tc-99m RBC studies, GI
bleeding is seen as an initial focus of increased radiotracer activity that on
subsequent images increases in intensity and changes position in a pattern that
confirms to segments of bowel. We report a case of a patient with multiple
episodes of GI bleeding referred to detect the source of bleeding. A Tc-99m
labeled RBC scan was performed and the findings showed a focal abnormal hot spot
in the mid quadrant of the abdomen, seen promptly in initial dynamic images.
Subsequent static and single-photon emission computed tomography-CT (SPECT-CT)
images found it to be umbilical varices. Most varices fill promptly as in this
case and should not be misinterpreted as a focus of hemorrhage. SPECT-CT should
be used in such cases so that that false-positive interpretation can be avoided.
PMID- 29962727
TI - Spontaneous Resolution of Idiopathic Panniculitis: Role of 18F-Fluorodeoxyglucose
Positron Emission Tomography/Computed Tomography in Diagnosis and follow-up.
AB - We present the case of a-55-year-old female patient who presented with dry cough.
High-resolution computed tomography chest revealed multiple nodules in both
lungs. 18F-fluorodeoxyglucose positron emission tomography/computed tomography
(PET/CT) was done to look for the unknown primary. It showed hypermetabolic
bilateral lung nodules, subcutaneous nodules involving lower limbs, an
intramuscular nodule, enlarged paratracheal, and right axillary nodes. There was
no primary tumor seen. The biopsy of subcutaneous nodule revealed panniculitis
with the foreign body granuloma. Follow-up scans after 6 and 9 months showed
spontaneous resolution of all lesions except for few right axillary nodes. There
was no active treatment given, and the patient remains asymptomatic on follow-up.
Here, PET/CT played a role in excluding a primary tumor, guiding the biopsy, and
follow-up.
PMID- 29962728
TI - 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Imaging
of Inferior Vena Cava Tumor Thrombus Extending into the Right Atrium in a Patient
with Cholangiocarcinoma Treated with 90Y-Microspheres.
AB - We present a case of a 42-year-old male patient affected by unresectable,
chemorefractory cholangiocarcinoma, with prior placement of biliary stent.
Because of the absence of extrahepatic metastases, he was submitted to liver
direct therapy with 90Y-microspheres. 18F-fluorodeoxyglucose positron emission
tomography-computed tomography (FDG PET-CT) performed before the procedure showed
intense tracer uptake in the hepatic lesion and along the biliary stent. The
patient underwent radioembolization with 90Y-resin spheres (1.1 GBq). 18F-FDG PET
CT, acquired 6 weeks after the procedure, showed no response of the hepatic
lesion and the appearance of an area of markedly increased uptake extending
through the inferior vena cava into the right atrium, confirmed as extensive
tumor thrombus at the enhanced multislice CT subsequently performed. 18F-FDG PET
CT proved to be a useful imaging tool not only for the evaluation of metabolic
response but also for the early detection of extrahepatic progression after 90Y
radioembolization.
PMID- 29962729
TI - Hematoma in Urinary Bladder Masquerading as Neoplastic Mass.
AB - The most common reason for intraluminal urinary bladder hematoma is trauma.
However in gynecological and pelvic malignancies, the pelvic irradiation can
affect non targeted organs resulting in urogenital complications like hematoma.
Small size hematoma can be easily diagnosed in ultrasound. Large hematoma can
mimic as neoplastic mass in imaging modalities. We present here an intresting
image of intraluminal urinary bladder mass, where FDG PET CT was helpful to
diagnose it as a non neoplastic mass.
PMID- 29962730
TI - Facial Dysmorphism Due to Multiple Brown Tumors Secondary to Large Parathyroid
Adenoma, Diagnosed on 99mTc-Sestamibi Parathyroid Scintigraphy.
AB - Brown tumors are an uncommon entity associated with hyperparathyroidism.
Initially described with primary hyperparathyroidism, with the widespread use of
dialysis, they were also seen to be associated with secondary and tertiary
hyperparathyroidism. These are lytic, expansile lesions causing bony pains, and
depending on the size and extent, skeletal dysmorphism. The present case
illustrates the detection of parathyroid adenoma with multiple brown tumors on
99mTc-sestamibi parathyroid scintigraphy in a patient presenting with facial
dysmorphism and multiple bony pains.
PMID- 29962731
TI - Demonstration of 68Ga-prostate-specific Membrane Antigen Uptake in Metastatic
Pancreatic Neuroendocrine Tumor.
AB - We present the case of a 47-year-old female with metastatic pancreatic
neuroendocrine tumor (NET). The patient was treated with long-acting octreotide
which failed to halt disease progression. The patient was being considered for
177Lu-peptide receptor radionuclide therapy, and a 68Ga-DOTANOC positron emission
tomography-computed tomography (PET-CT) was acquired initially, which showed good
uptake in the primary and metastatic lesions. Metastatic pancreatic NETs have
limited treatment options, and given the background that these tumors are highly
vascular and prostate-specific membrane antigen (PSMA) expression is known in the
endothelium of tumor neovasculature, we decided to perform a 68Ga-PSMA-HBED-CC
PET-CT scan. It revealed radiotracer uptake in the metastatic liver lesions
although not as high as 68Ga-DOTANOC-PET-CT. PSMA expression needs to be
researched further, especially in high-grade NETs where somatostatin expression
may be poor.
PMID- 29962732
TI - Carotid Body Tumor Masquerading as Metastatic Cervical Lymph Node on
Fluorodeoxyglucose Positron-emission Tomography-Computed Tomography.
AB - Carotid body tumors, although representing about 65% of head and neck
paragangliomas, are rare neoplasms. Doppler ultrasonography, contrast-enhanced
computed tomography (CECT), and MRI have been routinely used in the diagnosis of
carotid body tumor. We hereby represent a case of 56-year-old male suspected to
have lymph node metastasis from carcinoma pyriform sinus detected as carotid body
tumor in fluorodeoxyglucose positron-emission tomography-CECT imaging and
subsequently confirmed by histopathology.
PMID- 29962733
TI - Prostate-specific Membrane Antigen Imaging in Recurrent Medullary Thyroid Cancer:
A New Theranostic Tracer in the Offing?
AB - Prostate-specific membrane antigen (PSMA) expression has been shown in
neovasculature of various malignancies. Recurrent medullary thyroid cancer (MTC)
is difficult to treat. We present the findings on PSMA-positron emission
tomography/computed tomography (PET/CT) of a 68-year-old man with MTC, who
presented with a recurrent left paratracheal mass and rising calcitonin. The scan
revealed significant uptake on PSMA imaging but not on 68Ga-DOTANOC PET/CT. 177Lu
PRRT is one of the therapeutic options in patients with recurrent MTC, but in
this case was not possible due to lack of somatostatin receptor expression.
Imaging evidence of PSMA expression alerts us to the potential use of 177Lu-DKFZ
PSMA-617 therapy in such patients.
PMID- 29962734
TI - Bladder Leiomyoma: A Rare Differential and a Potential Pitfall in the Evaluation
for a Bladder Mass in 18F-Fluorodeoxyglucose-Positron Emission
Tomography/Computed Tomography.
AB - 18F-Fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG
PET/CT) has shown an increasing role in the evaluation of urinary bladder cancer,
though benign pathological processes of the urinary bladder can also result in
increased FDG uptake. Leiomyomas of urinary bladder are benign mesenchymal
neoplasms and a very rare bladder tumor comprising <0.5% of all bladder tumors.
Here, we present the low-grade 18FDG uptake in urinary bladder leiomyoma on
PET/CT done for the clinical suspicion of bladder cancer, which can be a rare
differential for bladder carcinoma.
PMID- 29962735
TI - Role of Preablative-Stimulated Thyroglobulin in Prediction of Nodal and Distant
Metastasis on Iodine Whole-body Scan.
PMID- 29962736
TI - Reply by the Author.
PMID- 29962737
TI - Erratum: The Radioprotective Effects of Curcumin and Trehalose Against Genetic
Damage Caused By I-131.
AB - [This corrects the article on p. 99 in vol. 33, PMID: 29643668.].
PMID- 29962738
TI - Role of Domiciliary Noninvasive Ventilation in Chronic Obstructive Pulmonary
Disease Patients Requiring Repeated Admissions with Acute Type II Respiratory
Failure: A Prospective Cohort Study.
AB - Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD)
with acute hypercapnic respiratory failure (AHRF) is associated with high
mortality and increased risk for further exacerbations and hospitalization. While
there is ample evidence regarding the benefit of noninvasive ventilation (NIV)
during AECOPD, evidence supporting long-term noninvasive ventilation (LTNIV) for
more stable COPD patients is limited. Objective: The aim of this study is to
assess the effectiveness of LTNIV in COPD patients requiring frequent hospital
admissions and NIV support for AHRF. Materials and Methods: A prospective cohort
study including 120 patients having survived an admission requiring NIV support
for AHRF due to COPD, with a history of >=3 similar episodes in the past year.
Patients were advised LTNIV (30) with standard treatment, or (90) standard
treatment alone. Both groups were followed up for 1 year. Among non-NIV group 10
died, and 8 lost follow-up, whereas two died in NIV group. The primary endpoint
was death. Data of remaining 100 patients were analyzed for other objectives
number of readmissions, AHRF, Intensive Care Unit (ICU)/ventilator requirement,
dyspnea, quality of life, exercise tolerance, lung function, and arterial blood
gases. Results: LTNIV group had 40% reduction in mortality (6.6% vs. 11.1%).
There was significant reduction in number of hospital admissions (28.6% vs.
84.7%: P <0.05), ICU admissions (7.1% vs. 56.9%: P = 0.01), ventilator
requirement (3.6% vs. 30.6%: P = 0.003), AHRF (7.1% vs. 48.6%: P = 0.000) and
improvement in partial arterial CO2 pressure (39.8 +/- 2.1 vs. 57.03 +/- 3.7
mmHg) and severe respiratory insufficiency score (P < 0.05) among LTNIV group,
but no significant change in lung function and exercise tolerance. Conclusion:
Patients tolerated LTNIV well and had a better outcome compared to those without
NIV. LTNIV may be considered in patients with recurrent AHRF.
PMID- 29962739
TI - Levels and Diagnostic Value of Model-based Insulin Sensitivity in Sepsis: A
Preliminary Study.
AB - Background and Aims: Currently, there is a lack of real-time metric with high
sensitivity and specificity to diagnose sepsis. Insulin sensitivity (SI) may be
determined in real-time using mathematical glucose-insulin models; however, its
effectiveness as a diagnostic test of sepsis is unknown. Our aims were to
determine the levels and diagnostic value of model-based SI for identification of
sepsis in critically ill patients. Materials and Methods: In this retrospective,
cohort study, we analyzed SI levels in septic (n = 18) and nonseptic (n = 20)
patients at 1 (baseline), 4, 8, 12, 16, 20, and 24 h of their Intensive Care Unit
admission. Patients with diabetes mellitus Type I or Type II were excluded from
the study. The SI levels were derived by fitting the blood glucose levels,
insulin infusion and glucose input rates into the Intensive Control of Insulin
Nutrition-Glucose model. Results: The median SI levels were significantly lower
in the sepsis than in the nonsepsis at all follow-up time points. The areas under
the receiver operating characteristic curve of the model-based SI at baseline for
discriminating sepsis from nonsepsis was 0.814 (95% confidence interval, 0.675
0.953). The optimal cutoff point of the SI test was 1.573 * 10-4 L/mu/min. At
this cutoff point, the sensitivity was 77.8%, specificity was 75%, positive
predictive value was 73.7%, and negative predictive value was 78.9%. Conclusions:
Model-based SI ruled in and ruled out sepsis with fairly high sensitivity and
specificity in our critically ill nondiabetic patients. These findings can be
used as a foundation for further, prospective investigation in this area.
PMID- 29962740
TI - Sleep Quality and Quantity in Intensive Care Unit Patients: A Cross-sectional
Study.
AB - Introduction: Lack of restorative sleep and altered sleep-wake cycle is a
frequent problem among patients admitted to the Intensive Care Unit (ICU). This
study was conducted to estimate the prevalence of poor sleep and patient's
perspective of factors governing poor sleep in the ICU. Materials and Methods: A
cross-sectional study was performed in medical ICU of a tertiary care hospital. A
total of 32 patients admitted to the ICU for at least 24 h were recruited. A 72-h
actigraphy was done followed by a subjective assessment of sleep quality by the
Richards-Campbell Sleep Questionnaire (RCSQ). Patient's perspective of sleep
quality and quantity and possible risk factors for poor sleep were recorded.
Results: Poor sleep (defined as RCSQ <50, sensitivity 88% and specificity 87%)
was found in 15 out of the 32 patients (47%). The prevalence of poor sleep was
higher among patients on mechanical ventilation (n = 15) (66.7% vs. 33.3%, P <
0.05). Patients with poor sleep had higher age (median age [in years] 42.8 vs.
31.4, P = 0.008), acute physiology, and chronic health evaluation II score (mean
14 +/- 5.15 vs. 9.3 +/- 5.64, P = 0.02), SAPS 3 score (62.7 +/- 8.9 vs. 45.6 +/-
10.5, P <= 0.0001), and worse actigraphy parameters. Only 55.63% of total sleep
time was in the night (2200-0600). All patients had discomfort from indwelling
catheters and suctioning of endotracheal tubes. All patients suggested that there
be a minimum interruption in the sleep for interventions or medications.
Conclusion: There is a high prevalence of poor sleep among patients admitted to
the ICU. There is a dire need to minimize untimely interventions and design
nonpharmacological techniques to allow patients to sleep comfortably.
PMID- 29962741
TI - Determining and Comparing Predictive and Intensity Value of Severity Scores -
"Sequential Organ Failure Assessment Score," "Acute Physiology and Chronic Health
Evaluation 4," and "Poisoning Severity Score" - in Short-Term Clinical Outcome of
Patients with Poisoning in an ICU.
AB - Introduction: Today, poisoning is one of the problems of society and it is always
one of the ten leading causes of death among youth. This study aimed to determine
and compare the predictive and intensity value of three standard criteria of
"Sequential Organ Failure Assessment (SOFA) score," "Acute Physiology and Chronic
Health Evaluation (APACHE) 4," and "Poisoning Severity Score (PSS)" in short-term
clinical outcome of poisoned patients. Methods: The prospective study conducted
on 120 patients of critical care units. Data were collected using a demographic
form and three criteria forms. The researcher was visiting the critical care unit
daily and was filling out the demographic form of each patient in the first 24 h
of hospital admission. The data were analyzed using SPSS version 16. Results: The
results showed the mean age of patients was 35.73 +/- 18.46 years with the most
frequency among male patients (66.7%). The mean of criteria scores of "SOFA
score," "APACHE 4," and "PSS" was 7.3 +/- 2.97, P = 0.009; 62.43 +/- 12.48, P =
0.58; and 2.4 +/- 0.5, P = 0.001, respectively. The accuracy, sensitivity,
specificity, positive and negative predictive values, and area under the curve of
"SOFA score," "APACHE 4," and "PSS" were 86.2, 70.6, 94.4, 98.6, 36.2, 0.897;
83.5, 90.2, 44.4, 90.2, 44.4, 0.808; and 16.7, 100, 2, 100, 15.3, 0.786,
respectively. Predicted mortality rate in "SOFA score" and "APACHE 4" was 18.7%
+/-20.2% and 2.63% +/-2.6%, respectively. Real mortality rate, predictive
duration of hospitalization by APACHE 4 criteria, and real duration of
hospitalization were 15%, 1.79 +/- 1.35, and 4.04 +/- 4.08, respectively.
Conclusion: The study showed that "SOFA score" was more predictive in clinical
outcomes due to poisoning and it is recommended to poisoning centers as effective
criteria.
PMID- 29962742
TI - A Prospective Antibacterial Utilization Study in Pediatric Intensive Care Unit of
a Tertiary Referral Center.
AB - Purpose: Antibacterials are commonly prescribed to Pediatric Intensive Care Unit
(PICU) patients. However, inappropriate antibacterial prescriptions lead to
increases in antibacterial resistance, treatment cost, duration of treatment, and
poor clinical outcome. The antibacterial utilization study assesses the
prescription patterns and if necessary recommends the interventions to improve
antibacterial prescriptions. Hence, the present prospective groundwork was
conducted. Materials and Methods: The study was conducted over the period of 6
months (April 18 to October 20, 2014). The demographics and drug use details were
captured daily from patients admitted to PICU to assess World Health Organization
indicators. Results: A total of 200 patients enrolled, among them 119 males and
81 females. There were 12.46 (+/-6.16) drugs prescribed per patient, of which
2.38 (+/-1.48) were antibacterials. Among the total drug prescribed, 18.49% were
antibacterials and 97% patients received at least one antibacterial. Ceftriaxone
(49.48%) was the most commonly prescribed antibacterial, while imipenem (2.58%)
and colistin (2.06%) use was very low. A total of 80.95% antibacterials were
prescribed by generic name, 94.88% were administered intravenously, and 80.76%
were prescribed from hospital pharmacy. The average length of PICU stay was 6.15
days (+/-6.20), the average length of antibacterial treatment was 6.08 days (+/
6.27), and the average length of empirical antibacterial treatment was 5.50 days
(+/-5.40). The cost of antibacterial therapy per patient was Indian rupees 824.64
(+/-235.35). In 27 patients, bacterial culture test was positive and of whom 21
received antibacterials as per sensitivity pattern. Conclusions: The use of
antibacterials was not indiscriminately high but more prescriptions per
sensitivity pattern are required.
PMID- 29962743
TI - Speech and Swallowing Function Outcome Following Early Tracheostomy in Patients
Who Underwent Neurosurgical Intervention.
AB - Background: Evaluation of late-onset speech and swallowing complications of
tracheostomy on neurotrauma cases, as the most common intensive care unit
procedure, needs to be evaluated. Objectives: A prospective study conducted in a
tertiary care teaching hospital to find the late-onset speech and swallowing
complications of tracheostomy in neurotrauma cases. Materials and Methods: This
prospective observational study was conducted in the intensive care unit on
intubated patients needing elective tracheostomy at a tertiary care teaching
institute in South India with a dedicated referral trauma center. A data
collection tool was prepared to find age, gender, date of admission,
tracheostomy, and discharge, contact address and number, initial and final
diagnosis, initial Glasgow Coma Scale (GCS) on admission and subsequent GCS
before and after tracheostomy, ventilator settings before and after the
tracheostomy, procedure and intraoperative complications, type of cannula used,
details of decannulation, and respiratory difficulties. Results: In our study
among 69 cases between 16 and 75 years' age range with mean 46.67 +/- 16.65,
majority were males (75.36%) and 60 were cranial cases (86.96%). Of the alive
cases (21 [30.43%]) who underwent tracheostomy; 18 were performed in operation
theater and 3 as bedside procedure. Major problems reported were: Speech problems
(not able to phonate) (9), feeble voice (6), pain while speaking (6), and reduced
loudness (6), frequent throat clearing while speaking (4), cough while speaking
(3); breathlessness while speaking (1), gasping while speaking (1) and vocal
tiredness (1); aspirations (2) and painful swallowing (1). Conclusions: Our study
suggested that though, majority of neurotrauma patients require tracheostomy for
long term ventilator support and associated speech and swallowing problems are
expected.
PMID- 29962744
TI - Study on Clinical Profile and Predictors of Mortality in Cerbera odollam
Poisoning.
AB - Context: Cerbera odollam is a tree native to South Asia. It belongs to the
poisonous Apocynaceae family. Deliberate self-harm with fruit of this plant is a
major clinical problem in the developing world. Ingestion of C. odollam kernels
is the cause of deaths in more than half of Kerala's plant poisoning deaths. The
data on clinical features and complications of C. odollam poisoning are sparse,
apart from a few case reports and limited studies. Aims: The present study was
done to find the mode of presentation, complications, need for cardiac pacing,
inhospital mortality, and the predictors of mortality in patients with C. odollam
poisoning. Settings and Design: This was a retrospective study conducted in the
department of general medicine in a tertiary care center in Alappuzha district,
Kerala. The study period was for 1 year from January 1, 2016, to December 31,
2016. Subjects and Methods: All the patients admitted with a history of ingestion
of odollam during the study period were included in the study. Data were
collected from case records. The study was approved by the institutional ethics
committee and research committee (IEC/TDMCA/EC3.dated29/11/201). Statistical
Analysis Used: The data were analyzed using SPSS 16 for Windows (SPSS Inc.,
Chicago, IL, USA). Results: In this study, 102 patients were identified with C.
odollam poisoning, and the mortality rate was 16.7%. Electrocardiogram (ECG)
changes were common in our patients, and we observed different types of heart
block in the same ECG itself. Ingestion of more than two kernels of odollam, late
presentation to hospital, vomiting, bradycardia, hypotension, hyperkalemia, and
more severe ECG changes were associated with significantly higher mortality in
this study. Conclusions: C. odollam poisoning is a common method of deliberate
self-harm in Kerala. It carries a high mortality rate, and the predictors of
mortality include vomiting, bradycardia, hypotension, hyperkalemia, and the
presence of severe ECG changes.
PMID- 29962745
TI - Comparison of Lung Ultrasound-based Weaning Indices with Rapid Shallow Breathing
Index: Are They Helpful?
AB - Background and Aims: The diaphragm is considered the main respiratory muscle and
difficulty in weaning can occur because of impaired diaphragmatic function.
Hence, monitoring diaphragmatic function is important. The aim of this study is
to assess the ability of various lung ultrasound (US) indices and the rapid
shallow breathing index (RSBI) to predict the outcome of the weaning process and
compare them with RSBI. Materials and Methods: This was a prospective study
conducted on patients admitted to critical care unit at a tertiary care hospital
in north India from February 2017 to June 2017. Patients were put to spontaneous
breathing trial (SBT) when they met the weaning criteria. Initial US was done
immediately after putting the patient on SBT to check anatomy of the diaphragm
and rule out patients according to exclusion criteria. This was followed by
complete lung US (LUS) after 20 min of SBT. Results: The RSBI performed better
than all other parameters, with an area under the curve (AUC) of 0.996. The
sensitivity and specificity is 100%. Only comparable to RSBI is the speed of
diaphragmic contraction (DC) which has AUC of 0.93. All other parameters had an
AUC <0.8. Moreover, the DC and LUS score are strongly positively correlated with
RSBI, whereas diaphragmic excursion and diaphragmic thickness fraction (DTF %)
are weakly correlated. Conclusion: In Intensive Care Unit, RSBI is the best
clinical tool for weaning, and DC is found to be the best parameter for weaning
among the US-based weaning parameters. It can even be a substitute for RSBI, in
today's world of real-time monitoring methods.
PMID- 29962746
TI - A Comparative Study of Midazolam and Target-Controlled Propofol Infusion in the
Treatment of Refractory Status Epilepticus.
AB - Background: The recommended treatment for refractory status epilepticus (RSE) is
the use of anesthetic agents, but evidence regarding the agent of choice is
lacking. This study was designed to compare target-controlled infusion of
propofol versus midazolam for the treatment of RSE regarding seizure control and
complications. Methods: This prospective, randomized study recruited 23 adult
patients with RSE due to any etiology and treated with either propofol or
midazolam titrated to clinical seizure cessation and gradual tapering thereafter.
The primary outcome measure was seizure control and the secondary outcomes were
duration of the Intensive Care Unit stay and duration of mechanical ventilation,
occurrence of super RSE (SRSE), and complications. Results: We recruited 23
patients (male:female = 18:5) into this study (propofol Group-11; midazolam Group
12). Overall, seizure control was noted in 34.8%, with successful seizure control
in 45% of patients in the propofol group and 25% in midazolam group (P = 0.4).
Mortality was similar in both the groups (propofol group [8/11; 72.7%] compared
to the midazolam group [7/12; 58.3%] [P = 0.667]). The duration of hospital stay
was significantly shorter in the propofol group compared to midazolam (P = 0.02).
The overall incidence of SRSE was 69.5% in this study. The complication rate was
not significantly different between the groups. Conclusions: The choice of
anesthetic agent does not seem to affect the overall outcome in RSE and SRSE.
Target-controlled propofol infusion was found to be equal in its efficacy to
midazolam for the treatment of RSE. High mortality might be due to SRSE secondary
to the underlying brain pathology.
PMID- 29962747
TI - Is My Patient Still Alive?
AB - The modern-day health-care firmament is fighting one of its biggest battles of
mistrust, the seeds of which have been sown over the years and the roots seem to
run deep. There is a substantial misunderstanding about the complexities of
intensive care treatments, especially the life support interventions. A
critically ill patient on ventilator is often perceived by the families to be
dead. Such misconceptions have a huge negative impact on the already friable
doctor-patient relationship. The paper presents an overview of the problem and
deliberates on the possible theories of such misunderstandings and chariness. An
attempt is made to suggest the steps that could be taken to address this
complicated issue.
PMID- 29962748
TI - Hepatomyoencephalopathy Secondary to Cassia occidentalis Poisoning: Report of
Three Cases from North India.
AB - Cassia occidentalis is an annual tropical shrub causing toxicity in cattle.
However, human case reports of its poisoning are scarce. We, here, report three
young children, residents of Western Uttar Pradesh in North India, who presented
with lethargy, jaundice, and altered sensorium after consumption of Cassia seeds.
The toxidrome was defined as hepatomyoencephalopathy. The children were
resuscitated, managed for acute liver failure, and subsequently discharged
without sequel. Although few studies have previously documented this association,
this is the first such case series documenting a direct causal relationship of
Cassia to hepatomyoencephalopathy syndrome. Public and clinician awareness
regarding this syndrome mimicking viral encephalitis has the potential to prevent
further outbreaks.
PMID- 29962749
TI - Therapeutic Red Cell Exchange Transfusion as an Adjuvant Therapy for Management
of Sickle Cell Crisis in Adults.
AB - Sickle cell crisis is an acute clinical condition, caused due to capillary
occlusion by the deformed red blood cells, leading to vaso-occlusive status. Vaso
occlusion is an emergency condition requiring intensive care admission and
carries a high mortality. Sickle cell crisis is usually managed with hydration,
analgesics, and supportive care. Therapeutic red cell exchange transfusion is
advised as an adjuvant, for the management of sickle cell crisis, and it is
mainly practiced in the pediatric population. We report an adult case of sickle
cell crisis managed with therapeutic red cell exchange transfusion in Intensive
Care Unit and successful outcome in patient management.
PMID- 29962750
TI - Keep an Eye on the Intracranial Pressure, Thanks to the Optic Nerve Sheath
Diameter.
AB - Neurological examination on sedated patients is challenging and no gold standard
monitoring is currently available. We report the case of a patient deeply sedated
for the management of acute respiratory distress syndrome secondary to pneumonia.
Delay in awakening led to cerebral exploration by transcranial Doppler (TCD) and
measurement of optic nerve sheath diameter (ONSD). Abnormal values of ONSD
prompted immediate brain computed tomography scan that confirmed high
intracranial pressure (ICP) due to multiple deep parenchymal hematomas. Despite
raised ICP, values obtained by TCD were normal, thanks to the persistence of
cerebral autoregulation. This case highlights the interest of combining
noninvasive techniques for neurological examination, especially for sedated
patients.
PMID- 29962751
TI - Hyperammonemia Presenting as Refractory Status Epilepticus after Lung Transplant
in a Patient Positive for Ureaplasma parvum.
AB - Hyperammonemia is a rare complication of lung transplant with a high mortality
rate. It presents as encephalopathy and progresses to seizures, status
epilepticus, coma, cerebral edema, and brain death. Multiple treatments have been
documented including administration of medications, gut decontamination, and
dialysis. However, no definitive treatments exist and mortality remains between
67% and 75%. We present the case of a 65-year-old male with idiopathic pulmonary
fibrosis who developed refractory status epilepticus secondary to hyperammonemia
following lung transplant. The patient presented on postoperative day 7 with
super-refractory status epilepticus and normal computed tomography scan of the
head. Hyperammonemia was suspected due to refractory seizures and confirmed with
peak ammonia level >1000 MUmol/L. Despite aggressive treatment, the patient
developed global cerebral edema and died. Postmortem investigations revealed that
the patient was positive for Ureaplasma parvum. Additional studies are needed to
elucidate the exact mechanism of disease and investigate successful treatment
options.
PMID- 29962752
TI - Fatal Cerebellar Hemorrhage Complicating Pneumococcal Meningitis: Are
Anticoagulants the Hidden Enemy?
PMID- 29962753
TI - A Letter in Response to "Diagnosing Catheter-Associated Urinary Tract Infection
in Critically ill Patients: Do the Guidelines Help?"
PMID- 29962754
TI - Ultrasonography-Guided Internal Jugular Venous Catheterization: Unusual Position
and Unusual Circumstances.
PMID- 29962755
TI - Commensalism the new Scientific Revolution?
PMID- 29962756
TI - Characterization of Herbal Antifungal Agent, Origanum vulgare against Oral
Candida spp. Isolated from Patients with Candida-Associated Denture Stomatitis:
An In vitro Study.
AB - Background: Candida Associated Denture Stomatitis is the prevalent fungal
pathosis in denture wearers, especially in immunocompromized patients. Existing
antifungal agents are ineffective since the Candida species become resistant and
also, they become toxic. Origanum vulgare is a herbal plant with high anti-fungal
activity against Candida of blood and urine origin. However, it has never been
explored against Candida from oral cavity. Materials & Methodology: Dry leaves of
the plant were purchased and authenticated. Oil extraction was done using Hydro
distillation method. Clinical isolates of Candida from denture wearers was
speciated using CHROMagar. Well Diffusion test was used to confirm the antifungal
activity. Hydro-distillation & Maceration methods of extraction were compared.
MIC/MFC was determined using CSLI guidelines. Infra-Red Spectroscopy was used to
identify the active functional group. Results: O.vulgare showed 30+/-3mm of zone
of inhibition as against 19mm for fluconazole. The suitable extraction method was
Hydro-distillation. MIC & MFC were found to be 0.024% and 0.097% respectively
which was much lesser than for fluconazole (0.25%). The active functional group
had chemically similar structure as Carvacrol, usually found in antifungal herbs.
Conclusion: within the limitations of the study, it was concluded that
(a)O.vulgare is anticandidal for clinical isolates of oral Candida, (b) Hydro
distillation is an effective method as compared to Maceration (c) MIC & MFC are
much lower than that of fluconazole (d) the major functional group was
structurally similar to Carvacrol.
PMID- 29962757
TI - Effect of Initial Periodontal Therapy on Salivary Trefoil Factor (TFF3) in
otherwise Healthy Patients with Gingivitis and Chronic Periodontitis.
AB - Background: The search for an ideal biomarker which can determine the current
disease status that predicts the sites and individuals with increased
susceptibility to periodontal disease has been going on since a long time. One
such group of molecules which have been investigated recently are the trefoil
factors, and the present study aims to determine the role of salivary trefoil
factor 3 (TFF3) in periodontitis and gingivitis patients. Materials and Methods:
A total of fifty participants, of which 25 were diagnosed with moderate-to-severe
periodontitis and 25 with chronic gingivitis were included in the study. The
routine periodontal parameters were recorded at baseline and at 6 weeks which
included plaque index, gingival index, bleeding index, probing depth, and
clinical attachment level. The saliva samples were collected from both the groups
at baseline and 6 weeks after nonsurgical periodontal therapy and analyzed by
enzyme-linked immunosorbent assay to estimate the concentration of trefoil factor
3. Results: All the periodontal parameters improved at 6-week reevaluation in
both the groups. There was a significant change in the TFF3 levels in the
periodontitis group from baseline to 6 weeks, and the concentrations were found
to be higher following nonsurgical therapy, whereas the quantum of change in the
gingivitis group was negligible. The levels of TFF3 remained unchanged in those
periodontitis participants who required surgical intervention at the 6th-week
reevaluation. Conclusion: The estimation of TFF3 levels may aid in decision
making in the treatment strategy of patients with moderate-to-severe
periodontitis.
PMID- 29962758
TI - Cryosurgery: A Simple Tool to Address Oral Lesions.
AB - Aim: The study was aimed at evaluating the efficacy of cryosurgery in the
management of oral mucosal lesions. Time taken for healing, postoperative pain,
secondary infection, and recurrence of lesion was evaluated. Materials and
Methods: A total of 30 patients with oral mucosal lesions were included in the
study. The patients were evaluated for pain and postoperative infection which was
documented on the 1st, 3rd, 7th, 21st day after the procedure. Other parameters
such as healing time and scarring were assessed at 21st day. Recurrence of the
lesion was evaluated in the 3rd and 6th postoperative month. All these data were
statistically evaluated. Results: The pain and swelling which reduced mainly
during the 7th postoperative day which was highly significant. The discomfort of
the patient was relatively less. Only three patients showed delayed healing out
of all patients. Recurrence of lesion was noted in two cases which conclude to
about 6.7%. Conclusion: The cryosurgery is overall a better modality for
treatment of oral lesions as it is more reasonable with adequate success. The
procedure is relatively more acceptable and has shown to have a faster recovery.
PMID- 29962759
TI - Comparative Evaluation of Dentinal Caries in Restored Cavity Prepared By Galvanic
and Sintered Burs.
AB - Background: The occurrence of secondary caries is the most common reason for the
restorations failures. Aim: The aim of the study was to evaluate and compare the
anticaries effect of copper ions on the teeth restored with glass ionomer cement
(GIC) and composite restorations in the cavity prepared by galvanic and sintered
burs. Materials and Methods: A total of 40 premolars were divided into two halves
buccolingually. Class V cavity was prepared with sintered diamond burs and
galvanic diamond bur. Cavities were restored with either GIC or composite resin.
The monospecies artificial microbial caries model was selected for induction of
secondary caries. The lesions were measured at junction of restoration by
confocal laser scanning microscope. Results: The results were statistically
significant (P < 0.001) and suggested that the width of lesion was lowest in
cavity prepared by sintered bur and restored with composite resin. Conclusion:
The use of different burs in combination with various restorative materials
influence the occurrence and width of caries lesion.
PMID- 29962760
TI - A Comparative Evaluation of Efficacy and Efficiency of Grayson's Presurgical
Nasoalveolar Molding Technique in Patients with Complete Unilateral Cleft Lip and
Palate with Those Treated with Figueroa's Modified Technique.
AB - Background: Presurgical nasoalveolar molding (PNAM) has been used for aligning
and not only for approximating the maxillary alveolar segments preoperatively but
also for improving the nasal symmetry and therefore facilitates primary surgical
repairs in cleft patients. Aim: This study was conducted to compare the efficacy
and efficiency of Grayson's technique with Figueroa's modified presurgical
nasoalveolar technique in complete unilateral cleft lip and palate (UCLP)
infants. Materials and Methods: Twenty-two infants aged 10-15 days were randomly
divided into two equal groups: Group I treated with Grayson's PNAM technique and
Group II with Figueroa's PNAM technique. Results: When we compared nasal
asymmetry values preoperatively and postoperatively of Group I and Group II, it
was found that the nostril height increased significantly on the cleft side and
nostril width decreased significantly postoperatively on the cleft side. When we
compared nasal asymmetry values postoperatively of Group I with Group II, all the
values were nonsignificant. When we compared the digital maxillary cast analysis
outcomes preoperatively and postoperatively in Group I and Group II, it was found
that there was a significant reduction in the alveolar gap and there is a
significant increase in the arch width. When we compared the efficiency of Group
I with Group II, it was found that Group II was more efficient than Group II.
Conclusion: This study showed a morphological improvement in nasal symmetry and
maxillary alveoli of infants with UCLP treated with both Grayson's PNAM technique
and Figueroa's PNAM technique with Grayson's PNAM technique being more efficient.
PMID- 29962761
TI - Comparative Analysis of Apical Root Crack Propagation after Root Canal
Preparation at Different Instrumentation Lengths Using ProTaper Universal,
ProTaper Next and ProTaper Gold Rotary Files: An In vitro Study.
AB - Aim: To compare the incidence of apical root crack formation after root canal
preparation at different instrumentation lengths using ProTaper Universal (PTU),
ProTaper Next (PTN) and ProTaper Gold (PTG) file systems. Subjects and Methods:
Eighty-four mandibular first premolars with single and straight root canal were
mounted in resin block after simulating periodontal ligaments. 1-2 mm of root
apex was exposed followed by sectioning of 1 mm of root tip for better
stereomicroscopic visualization. While the Control group was left unprepared,
experimental groups were instrumented up to root canal length (RCL) and (RCL-1
mm) respectively using PTU, PTN and PTG. After staining the root apex with 1%
methylene blue dye, stereomicroscopic images were obtained for evaluating apical
root cracks. The data were analyzed using Chi-square, phi and Cramer test. The
significance level was set at P < 0.05. Results: Significantly less dentinal
defects were seen between PTG and PTU while there was no significant difference
between PTU-PTN and PTN-PTG. Furthermore, samples instrumented up to RCL-1 mm
showed lesser cracks as compared with samples instrumented up to RCL. Conclusion:
PTG produced least number of cracks followed by PTN and PTU. Furthermore,
instrumenting short of RCL reduced the crack formation risk.
PMID- 29962762
TI - Bond Strength of an Orthodontic Adhesive Containing an Antibiofilm Agent
(Octafluoropentyl Methacrylate).
AB - Objective: The objective of this study was to determine whether an adhesive
containing antibiofilm agent octafluoropentyl methacrylate (OFPA) has an
acceptable bond strength as an orthodontic adhesive. Methods: Sixty human
premolars were divided into four groups. In Groups 1 and 2, brackets were bonded
to the teeth using experimental nanohybrid adhesive containing OFPA (ENH-OFPA)
and Transbond XT (TXT) was used in Groups 3 and 4. In Groups 1 and 3, the samples
were stored in water at 37 degrees C for 24 h and in Groups 2 and 4 thermocycled
between 5 degrees C and 55 degrees C. The entire samples were debonded utilizing
a universal testing machine. Two-way ANOVA test employed to compare the shear
bond strength (SBS) between two adhesives. Independent Student's t-test was
utilized to compare the SBS at 24 h and followed thermocycling in each adhesive
group. Adhesive remnant index (ARI) evaluated in different groups using Chi
square test. Results: The mean value for SBS in ENH and TXT groups were 8.13 MPa
and 8.10 MPa, respectively. The inference of P = 0.260 was observed and concluded
to be nonsignificant for adhesives in terms of SBS. Statistically, differences
that observed in SBS at 24 h and following thermocycling in TXT (P = 0.288) and
ENH-OFPA (P = 0.145) groups did not consider to be significant. Comparing ARI
scores with bracket failure mode resulted in no significant difference (P = 1)
between two adhesives in both 24 h and following thermocycling. Conclusion:
Adding OFPA does not compromise SBS of the experimented orthodontic adhesive.
PMID- 29962764
TI - Bulk-Fill Restorative Materials in Primary Tooth: An Intrapulpal Temperature
Changes Study.
AB - Objectives: It was aimed to investigate the temperature changes in primary teeth
pulp chamber during the curing/setting of bulk-fill restorative materials with
different nanoparticle contents. Methods: Twenty-five extracted, primary
mandibular second molars were prepared as a Class II cavity. Five bulk-fill
restorative materials consisting of Equia Fil (HVGIC), glass carbomer (GC)
cement, Sonic Fill (SF), X-tra Fil (XF), and Quix Fil (QF) were tested. The
measurement of the pulp chamber temperature changes (starting temperature 37
degrees C) during setting/curing was performed with a J type thermocouple. The
data, differences between highest and initial temperature values, were recorded
and analyzed by one-way ANOVA. Results: The temperature changes in the pulp
chamber were in EF (2.81 degrees C), GC (7.92 degrees C), SF (3.33 degrees C), XF
(3.43 degrees C), and QF (3.02 degrees C). There were statistically significant
differences between temperature changes in groups (P < 0.05). Conclusion: The
tested bulk-fill resin composites and high-viscosity glass ionomer cement do not
increase the intrapulpal temperature in primary teeth during the curing/setting.
PMID- 29962763
TI - Ready to Use Norms for Arnett Bergman Soft-Tissue Cephalometric Analysis for
South Indian Population.
AB - Context: Variability of the soft-tissue drape in humans has complicated the
accuracy of evaluating soft tissue profiles in diagnosis and treatment planning.
Aims: The objective of the present study is to establish soft-tissue
cephalometric norms for South Indian population using Arnett Bergman Soft tissue
analysis. Settings and Design: This study was conducted at the Department of
Orthodontics and Dentofacial Orthopaedics. Subjects and Methods: Lateral
cephalograms of 60 individuals (30 males and 30 females), age ranging between 18
and 25 years, with orthognathic facial profiles were obtained in natural head
position. True vertical line was drawn through subnasale parallel to the vertical
reference plane. Measurements were done according to soft-tissue cephalometric
analysis. Statistical Analysis Used: Student's t-test was used to compare the
means between two groups. Results: The results of the study showed significant
gender dimorphism, with men having thicker soft-tissue structures, larger
vertical dimensions, deep-set midface structures, more upright incisors, and
deeper inferior labial sulci than women. When compared with the standard norms,
the South Indian population had significantly protruded dentition, thinner soft
tissue drape, shorter vertical face heights, prominent forehead and midface with
retusive lower facial thirds and convex profiles as compared to Caucasians.
Conclusions: Significant gender dimorphism was evident in the local population
suggesting the need for separate set of norms for males and females. Distinct
ethnic differences were found between Caucasians and the Indian population that
were statistically significant, highlighting the importance of defining separate
set of norms for ethnic groups. The norms obtained should be used as reference
when planning treatment of a specific ethnic group.
PMID- 29962765
TI - Comparative Evaluation of Remineralization Potential of Casein Phosphopeptide-
Amorphous Calcium Fluoride Phosphate and Novamin on Artificially Demineralized
Human Enamel: An In vitro Study.
AB - Aim: This study aimed to quantitatively compare the remineralization potential of
casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP) and Novamin
on artificially induced enamel subsurface lesions using scanning electron
microscope-energy dispersive X-ray (SEM-EDX). Materials and Methods: Enamel
specimens were prepared from seventy caries-free premolars and were kept for
demineralization for 4 days. Following demineralization, enamel specimens were
assigned to three groups: (1) Control group, (2) Group with CPP-ACFP-containing
toothpaste, and (3) Group with Novamin-containing toothpaste. Further, both the
experimental groups (CPP-ACFP group and Novamin) were then divided into three
subgroups based on the duration of re-mineralization as follows: (a) 7 days, (b)
14 days, and (c) 21 days. Enamel specimens of experimental groups were then
subjected to SEM-EDX to evaluate mineral content after treating with CPP-ACFP and
Novamin. Results: Both the experimental groups showed very high significant
differences between Ca/P ratios of remineralized samples. Conclusion: Even though
both CPP-ACFP and Novamin showed remineralization potential, remineralization was
found to be higher in the samples treated with CPP-ACFP.
PMID- 29962766
TI - Knowledge, Attitude, and Behavior Related to Use of Miswak (Chewing Stick): A
Cross-Sectional Study from Aseer Region, Saudi Arabia.
AB - Aim: The aim of this study was to assess the oral health knowledge, behavior, and
practices related to use of miswak (chewing stick) in population of Aseer Region,
Saudi Arabia. Subjects and Methods: Of the 2023 participants, 1666 (83.3%) were
females and 334 (16.7%) were males. The questionnaires having 10 online questions
were used to assess the knowledge of oral hygiene methods, including frequency,
reason, and methods for miswak use. Statistical Analysis Used: The survey data
were collected and organized into Microsoft Excel spreadsheets (Microsoft Inc.,
USA) and were statistically analyzed utilizing the Statistical Package for the
Social Sciences version 20.0 software (IBM Inc., USA). The statistical test used
here was the Chi-square test, and P < 0.05 was considered to be statistically
significant (P < 0.05). Results: Participants responded regarding the primary
oral hygiene methods; 46.5% respondents used toothbrushes, 44.5% used both
toothbrushing and miswak, and 8% used only miswak as their primary tooth cleaning
method. 28.2% respondents cleaned their teeth with tooth brush or miswak at least
once a day, 37.6% twice, 28.4% whenever required, and 5.9% infrequently. Majority
of the participants, i.e. 70.2% were using miswak with taper and as a brush to
clean all tooth surfaces. About 84.7% feel fresh, and teeth are whiter after the
use of miswak. Nearly, 84.7% prefer to continue using miswak in combination with
other teeth cleaning methods, which may have more benefits. Conclusions: In our
study, most common type of oral hygiene method employed is toothbrush and in
combination with miswak. Chewing stick use was common among participants with
religious advice being the dominant reason for usage.
PMID- 29962767
TI - In vivo Outcomes of Indirect Pulp Treatment in Primary Posterior Teeth: 6 Months'
Follow-up.
AB - Background: Indirect pulp treatment (IPT) is a minimally invasive procedure based
on the application of a protective liner on the affected dentin, thereby
preserving the pulp vitality. Aim: This study aims to evaluate and compare the
clinical and radiographic outcomes of IPT when a layer of calcium hydroxide
(Dycal), mineral trioxide aggregate (MTA), or Biodentine was placed over the
affected dentin in primary molars. Materials and Methods: A clinical trial with
sample size of 45 primary molars between the age group of 4-9 years, of which 15
teeth were considered, each for Group I (Dycal), Group II (MTA), and Group III
(Biodentine). Measurements on digitized radiographs were made at baseline, 3, and
6 months using Corel Draw software. Results: One-way ANOVA and post hoc tests
indicated a statistically significant difference in dentin thickness (P < 0.05)
in all the groups. Within Group I, the thickness of dentin was 0.066 +/- 0.009 mm
at 3 months and 0.099 +/- 0.011 mm at 6 months. In Group II, 0.081 +/- 0.010 mm
at 3 months and 0.123 +/- 0.016 mm at 6 months. In Group III, 0.102 +/- 0.021 mm
at 3 months and 0.154 +/- 0.022 mm at 6 months. Conclusions: Clinically, 100%
success rate was observed in all the groups whereas radiographically, Biodentine
was superior to both the groups.
PMID- 29962768
TI - Evaluation of pH and Chlorine Content of a Novel Herbal Sodium Hypochlorite for
Root Canal Disinfection: An Experimental In vitro Study.
AB - Introduction: Sodium hypochlorite (NaOCl) is widely used endodontic irrigant with
its array of advantages and disadvantages. Addition of herbal agents to NaOCl
might help in enhancing its efficacy. Materials and Methods: NaOCl was prepared
using chlorinated lime, anhydrous sodium carbonate, and distilled water to obtain
6% fresh solution. Then, this solution was evaluated for its pH and chlorine
content. The fresh herbal extract of Cymbopogon citratus (lemongrass), Mentha
piperita (peppermint), and Ocimum sanctum (tulsi) was prepared from plant leaves.
After which, various permutation and combinations were made, and it was found
that 9:1 ratio was the most effective combination. The pH and percentage of free
chlorine were evaluated and analyzed. Results: No statistical significant
difference was found in pH content. However, significant difference was found
between the groups for chlorine content (P < 0.05) of herbal NaOCl. Conclusion:
The current study presents a simplified method for preparation of herbal
irrigating solution.
PMID- 29962769
TI - Influence of External Chromophore on Cutting Efficacy of 940 nm Diode Laser: An
In vitro Animal Tissue Study.
AB - Background: High-power level lasers used in health sciences have important
photothermal effect. The maximum absorption of the diode laser correlates with
the absorption range of hemoglobin, suggesting that red color may be the required
chromophore. Hence, we hypothesized that by providing artificial external red
chromophore, we can improve the cutting efficiency of diode laser in noninflamed
tissue. The aim of the present study was to assess the efficacy and collateral
thermal damage produced by a 940 nm diode laser on stained and unstained porcine
tissue sample. Materials and Methods: Eight porcine meat samples of specific
dimensions were divided into four groups of two pieces each. Group I was stained
with beetroot extract, Group II stained with 3% erythrosine dye, Group III
stained with hibiscus extract, and Group IV left unstained. A 940 nm diode laser
was used at 1.2 W in an intermittent wave mode, to make a standardized dimension
incision in all the samples. One sample from each group was stored in 10%
formalin and sent for histopathological examination to evaluate the depth and
width of incision and amount of lateral thermal damage. The other sample from
each group was observed under video profilometer to evaluate the surface
characteristics. Results: Staining of tissues with external chromophore using 3%
erythrosine dye improved the efficacy of 940 nm diode laser, as evidenced from
the sharper, wider cuts and clean incision with minimal charring as compared to
beetroot, hibiscus, and saline. Conclusion: The use of staining can be an adjunct
to the lasers in improvement of efficacy.
PMID- 29962770
TI - Candida Species Diversity in Oral Cavity of Type 2 Diabetic Patients and their In
vitro Antifungal Susceptibility.
AB - Objective: To identify and compare the species variation and Colony Forming Units
of the species and antifungal susceptibility from oral rinse samples of
individuals in poorly-controlled, moderately-controlled and well controlled
diabetes patients with control group. Subjects and Methods: Study group comprised
of well-controlled, moderately-controlled and poorly controlled Type II diabetic
patients grouped according to the level of glycated hemoglobin concentration with
50 patients in each group and 50 healthy individuals. Oral rinse samples were
collected in a sterile container with phosphate-buffered saline and then
transported immediately for various mycological investigations and antifungal
susceptibility tests. Statistical analysis was performed. Results: There was a
significant difference in frequency of Candida in poorly controlled diabetes when
compared to moderately controlled diabetes, well controlled diabetes and normal
patients (P = 0.045). A higher number of colony count was seen among poorly
controlled diabetes than well controlled, moderately controlled and non diabetic
subjects. A comparatively low number of non-albicans were seen in healthy
individuals. C. albicans showed an increased resistance to fluconazole in DM
patients in comparison to control group (P = 0.001). Other species showed a
variable sensitivity pattern. Conclusion: The decreased immunity and change in
oral habitat in diabetic patients creates a diversification in various species of
Candida. These non albicans vary in their susceptibility and pathogenesis. A
definite identification of these diverse species in the oral cavity of such
patients and their susceptibility mandates proper management to avoid recurrence
and drug resistance.
PMID- 29962771
TI - Quantitative Evaluation of Midpalatal Suture Opening and Its Relation with
Zygomaticomaxillary Suture Status in Patients Aged 7-25 Years Using Cone Beam
Computed Tomography Images: In an Iranian Population.
AB - Objective: The purposes of this study were to determine the midpalatal suture
(MPS) opening depth and to assess its relation with the zygomaticomaxillary
suture (ZMS) by age with using cone beam computed tomography (CBCT). Materials
and Methods: In this cross-sectional study, 167 CBCT scans of patients aged 7-25
years (mean age: 16.04 +/- 5.17 years) were selected based on predefined criteria
and categorized into four age groups. The mean percentages of the depth of MPS
opening at anterior, middle, and posterior regions in the coronal and closure
status of ZMS in axial views were determined by a maxillofacial radiologist.
Results: The mean percentages of MPS opening depth at anterior, middle, and
posterior regions were 98.20%, 89.27%, and 71.44%, respectively. In these
regions, 20-25-year age group showed a significant difference compared with first
and second-age groups. A significant difference was observed in the frequencies
of complete MPS opening in different age groups in the middle (P = 0.017) and
posterior (P = 0.001) regions. About 80.20% patients had open ZMS bilaterally.
The percentages of opening depth in the three regions were 97.8%, 91.8%, and
75.6%, respectively, when ZMS was open on both sides. Conclusion: Percentage of
opening depth of this suture decreased by age. MPS closure starts from the
posterior region. ZMS in younger people is usually open on both sides; however,
it can be closed on one or both sides by age. An association was observed between
bilateral closure or opening of ZMS and mean percentage of MPS opening in the
middle and posterior regions.
PMID- 29962772
TI - Association of Elevated C-Reactive Protein with Severe Periodontitis in
Hypertensive Patients in Lagos, Nigeria: A Pilot Study.
AB - Background: Epidemiological studies have shown that individuals with chronic
periodontitis have a significantly higher risk of developing cardiovascular
complications, which might be attributed to the increased production of
inflammatory cytokines initiated by the complex microbiota in dental biofilm.
Aim: The study aims to evaluate the association between chronic periodontitis and
C-reactive protein (CRP) levels in a group of hypertensive individuals in
Nigeria. Materials and Methods: The investigator enrolled 50 hypertensive
patients with chronic periodontitis into the study from the medical outpatient
clinic of a teaching hospital in Lagos, Nigeria. Full-mouth periodontal
examination was done to assess the participant's periodontal status, with probing
depths and clinical attachment levels of six sites on all teeth. The investigator
defined periodontitis as at least one interproximal site with probing depth >=4
mm. Classification of participants into three groups was done based on their
severity of periodontitis; mild (n = 16), moderate (n = 27), and severe (n = 7)
periodontitis. Their CRP serum levels were measured, and the association with the
severity of periodontitis was determined. P was found to be <= 0.05. Results: The
median CRP levels were 1.0 (0.6, 2.2), 2.4 (1.1, 4.8), and 4.1 mg/L (3.3, 9.4)
for mild, moderate, and severe chronic periodontitis, respectively. The
association between the serum CRP levels and severity of periodontitis was
statistically significant (P = 0.006). Conclusion: There was an association of
elevated serum CRP level with increased severity of chronic periodontitis in
hypertensive individuals. This preliminary finding among Nigerians suggests that
chronic periodontal inflammation may contribute to systemic inflammatory burden
in hypertensive patients.
PMID- 29962773
TI - Correction of Secondary Alveolar Clefts with Iliac Bone Grafts.
AB - Introduction: Cleft lip and palate deformities are one of the most common birth
defects. The alveolar cleft requires bony repair to allow proper eruption of
dentition. The purpose of this study is to evaluate success in the repair of
alveolar clefts with iliac bone grafts. Aim: The aim of this study is to restore
the function and form of both arches with a proper occlusal relationship and
eruption of tooth in the cleft area. Subjects and Methods: Five patients were
selected irrespective of sex and socioeconomic status and whose age was within
the mixed dentition period. The iliac crest is grafted in the cleft area and
subsequently evaluated for graft success using study models, periapical, and
occlusal radiographs. Results: At the time of evaluation, teeth were erupted in
the area and good alveolar bone levels were present. Premaxilla becomes immobile
with a good arch form and arch continuity. There are no major complications
regarding pain, infection, paresthesia, and hematoma formation at donor site
without difficulty in walking. There is no complication regarding pain,
infection, exposure of graft, rejection of graft, and wound dehiscence at the
recipient site except in one case. Conclusions: Long-term follow-up is required
to achieve maximum advantage of secondary alveolar grafting; the age of the
patient should be within the mixed dentition period, irrespective of sex and
socioeconomic status. It may be unilateral or bilateral.
PMID- 29962774
TI - Correlation between Pulp Stones and Gall Bladder Stones: A Radiographic
Retrospective Case-Control Study.
AB - Background: Calcifications can occur in the dental pulp as discrete bodies known
as pulp stones. Their etiology remains obscure. They were believed to be formed
as a result of local irritating factors within the pulp; however, a few authors
now suggest that they may be a part of systemic biomineralization process that
affects many body parts such as kidneys, gall bladder, joints, arteries as well
as pulp leading to formation of stones. Aim: This retrospective case-control
study was taken up to (i) determine the prevalence of pulp stones as well as pulp
chamber narrowing in patients with gallbladder stones as well as the controls
(ii) whether any correlation exists between the prevalence of pulp stones and
gallbladder stones so as to test the hypothesis that pulp stones and gallbladder
stones may be a part of a common systemic calcification process. Setting and
Design: This retrospective case-control study was conducted in the Department of
Gastroenterology and Department of Radiodiagnosis, Sri Guru Ram Das Institute of
Medical Sciences and Research, Amritsar. A total of 200 individuals were taken up
for the study. Group I consisted of 100 patients (cases) with confirmed diagnosis
of gallbladder stones. Group II included the control group in which individuals
who were the close relatives of the patients with gall bladder stones were taken
(n = 100), so as to eliminate the common confounding factors in these two groups
such as diet, air, water, environment, genes, and age, which could affect the
formation of pulp stones could not be the reason for the formation of pulp
stones. Materials and Methods: Standard bitewing radiographs were taken for all
the patients in each group and presence or absence of pulp chamber narrowing and
pulp stones were observed. Statistical Analysis Used: McNemar's statistical test
was used to find the difference between the two groups, and the P value was
determined. Coefficient of association using the Phi coefficient was used to
determine if there was any association between the two groups. Results: In Group
I, 37% of the patients with gallbladder stones showed the presence of pulp
stones; whereas in the Group II which was the control, 57% of individuals showed
the presence of pulp stones. McNemar's test of significance calculated with one
degree freedom (1-df) showed that P = 0.01, thereby showing that there was a
significant difference between these two groups. Conclusion: According to the
study, a negative correlation between pulp stones and gallbladder stones was
found and they are not related to each other.
PMID- 29962775
TI - Alterations of Serum Lipid Profile Patterns in Oral Lichen Planus Patients: A
Case-Control Study.
AB - Background: Oral lichen planus (OLP) is a chronic disease of established immune
mediated pathogenesis. It most commonly, protractedly, and persistently involves
the mucosa of the oral cavity. Antigen-specific and nonspecific mechanisms play a
role in its pathogenesis, leading to T-cell accumulation in superficial lamina
propria, intraepithelial T-cell migration, and keratinocyte apoptosis in OLP.
Previous studies have indicated the possibility of serum lipid derangement in
chronic inflammatory diseases such as systemic lupus erythematosus and psoriasis,
which in turn results in elevated cardiovascular disease risk. Inflammation
causes disturbances in lipid metabolism such as decrease in high-density
lipoprotein-cholesterol (HDL-C) and increase in very low-density lipoprotein
(VLDL)-cholesterol and hypertriglyceridemia due to direct effect on T-cell
responses. Prolonged dyslipidemia, due to chronic inflammatory condition,
enhances the formation of atherosclerotic plaques and thereby augments the risk
of cardiovascular disease in such patients. With this background, a possible
correlation between OLP and serum lipid level derangement can be anticipated.
Hence, this study was taken up to probe into an association between the two.
Aims: To determine and compare the serum lipid levels in OLP patients and healthy
controls, to inquire into the possible association of OLP with alterations in
serum lipid profile patterns, and to determine if the clinical characteristics of
OLP differed with alterations in serum lipid profile patterns. Subjects and
Methods: Sixty patients comprising 30 cases and 30 controls were enrolled for the
study. Thirty cases of clinically and pathologically diagnosed OLP and 30 age-
and sex-matched controls were subjected to blood examination for the assessment
of serum lipid level, i.e., HDL, LDL, VLDL, and triglyceride. The obtained data
were compared with standard values to assess any alterations of the serum lipid
levels. Statistical Analysis Used: Cramer's V-test was performed for all the
tests to measure association between two nominal variables. A P <= 0.05 was
considered statistically significant. Results: Dyslipidemia was observed in 13
(46.67%) cases as against 7 (23.33%) controls. Thus, a significant number of
cases were found to have an associated serum dyslipidemia. However, pertaining to
individual serum lipid levels in cases and controls, the association was found to
be statistically insignificant. Conclusions: The current study suggested an
evident association between dyslipidemia and OLP. We recommend imminent studies
on a larger population to additionally substantiate a positive association
between the two.
PMID- 29962776
TI - Effect of Monopoly-coating Agent on the Surface Roughness of a Tissue Conditioner
Subjected to Cleansing and Disinfection: A Contact Profilometric In vitro Study.
AB - Introduction: Tissue conditioners are used to improve the health of the soft
tissues of denture-bearing areas. However, leaching of plasticizers from tissue
conditioners results in deterioration, which necessitates frequent replacement.
The life of these liners varies, but it can be extended by the use of a coating
material. Aim: To evaluate the surface roughness of a tissue conditioner with
monopoly coating, subjected to denture cleanser and disinfectant. Materials and
Methods: Sixty disk-shaped specimens of Visco-gel were made and divided into six
groups of 10 each (control 1 [C1], control 2 [C2], control 3 [C3], group 1 [M1],
group 2 [M2], and group 3 [M3]). Specimens of the control group were not coated
with monopoly, while the specimens of the groups 1, 2, and 3 were coated with
monopoly. Specimens of C1 and M1 were immersed in distilled water. Specimens of
C2, C3, M2, and M3 were immersed into solution of denture cleanser for 8 h at
room temperature and immersed in distilled water for the remainder of the 24-h
period. C3 and M3 specimens were treated with disinfectant for 10 min before
testing the surface roughness. The surface roughness was measured on 1st, 3rd,
5th, 7th, and 14th day, using a contact profilometer. Student's paired t-test was
used to compare the mean Ra values within each group. In the present study, P <
0.05 was considered as the level of significance. Results: The mean surface
roughness values of M1, M2, and M3 groups were less than C1, C2, and C3,
respectively. Among all the groups, M1 showed the least surface roughness values.
Conclusion: Monopoly-coating agent prevents the deterioration and reduces the
surface roughness of the tissue conditioner.
PMID- 29962778
TI - Evaluation of Anatomy and Root Canal Morphology of the Maxillary First Molar
Using the Cone-Beam Computed Tomography among Residents of the Moscow Region.
AB - Background: The success of endodontic treatment depends on the knowledge of root
canal system. The root canals have complex morphology and wide individual
variations. The aim of this study was to evaluate the root canal morphology of
the maxillary first molars among residents of the Moscow region using cone-beam
computed tomography (CBCT) scanning. Materials and Methods: Three hundred CBCT
images of patients aged 20-70 years old were analyzed to study the root canal
system (the number of canals and the configuration according to Vertucci's
classification) of the maxillary first molars. The prevalence of a second
mesiobuccal (MB2) in the mesiobuccal root (MB) was recorded in each age group.
Results: three separated roots of the maxillary first molar were observed in 100%
of cases. MB2 canals were found in 59.8% of cases. A second distobuccal canal was
observed in 0.5% of cases. The canal morphology in the MB root was 40.2% in Type
I, 22.4% in Type II, and 37.3% in Type IV. Conclusion: The prevalence of MB2
canals was 59.8%, and the most common canal morphology was Vertucci's Type I.
Using CBCT scanning is a useful technique to evaluate and analyze the root canal
system.
PMID- 29962777
TI - Trends in Selection, Usage, and Techniques of Interocclusal Record Materials
among Private Dental Practitioners: A Survey.
AB - Background: Majority of general dental practitioners provide fixed dental
prosthesis in India. The aim of this study was to gather information on
selection, usage, and materials and methods employed in interocclusal records and
their communication with the dental laboratory for restorative procedures
practised by dentists in Indore district to evaluate and to improve the quality
of current practice. Aim and Objectives: The purpose of this cross-sectional
study was to understand and to evaluate dental practitioner's knowledge on
interocclusal recording materials, its usage, their clinical implications, and
their correlation with the laboratory in restorative procedures practiced by the
dental practitioners in Indore district. Materials and Methods: A questionnaire
comprising 11 questions were framed and circulated among general dental
practitioners except prosthodontists, and the results were statistically
analyzed. Results: Most of the practitioner's preferred wax (54.6%) as an
interocclusal recording material over polyvinylsiloxane and polyether. Most of
the dentists preferred full arch interocclusal record (27.8%). About 51.5%
clinicians trimmed the interocclusal record before sending to the laboratory.
Conclusion: From this survey, it has been concluded that the practitioner's
attitude toward the use of interocclusal record materials is found to be deviated
from well-acknowledged prosthodontic quality guidelines.
PMID- 29962779
TI - An In Vitro Study to Evaluate and Compare the Flow Property of Different
Commercially Available Zinc Oxide Eugenol Impression Materials.
AB - Introduction: Impression making is one of the most important steps in
prosthodontic rehabilitation of edentulous patients. Zinc oxide eugenol (ZOE)
impression paste is the most commonly used material for complete denture wash
impression due to its cost-effectiveness and ease of manipulation, while
providing the advantage of ability to record fine minute tissue details.
Rheological property like flow is a critical factor influencing the success of
any impression material, especially in intraoral conditions. Therefore, with so
many brands of commercially available impression materials flooding the markets,
the aim of this study was to evaluate and compare the flow property of four
commercially available ZOE impression materials under simulated intraoral
condition. Materials and Methods: The testing method used was according to the
American Dental Association (ADA) specification no. 16 for ZOE impression pastes.
Results: At room temperature, maximum flow was seen with Denzomix followed by
Dental Product of India (DPI), Neogenate, and Cavex in descending order,
respectively, at 30 s, 1 min, and 10 min of load application. At 37 degrees C in
saliva, maximum flow was seen with Denzomix followed by Neogenate, DPI, and Cavex
in descending order, respectively, at 30 s, 1 min, and 10 min of load
application. Of the four ZOE impression pastes, only the flow of Cavex was
considerably less than ADA specified value. Interpretation and Conclusion:
Results obtained from this study showed that there is considerable variation in
the flow values of different commercially available ZOE impression materials.
Change in temperature and presence of saliva had a significant influence on the
flow of ZOE impression materials.
PMID- 29962780
TI - Evaluation of Mechanical Properties of Newer Nanoposterior Restorative Resin
Composites: An In vitro Study.
AB - Introduction: Tooth coloured restorative materials are subjected to various
physical, mechanical conditions in oral conditions. Many newer composites with
improved physical and mechanical properties are introduced for clinical use.
There are not many clinical studies on recent composites. The aim of this study
was to compare the mechanical properties of five commercially available nano
composite restorative materials. Materials and Methods: Specimens of five nano
posterior composite SureFil SDR, ClearFil Majesty, Ever X, Tetric Evo Ceram bulk
fill and Filtek Z350 were tested in the study. All samples were prepared
According ISO 4049 and polymerized with a LED light for 40 seconds and subjected
to mechanical tests for compressive strength, flexural strength, flexural
modulous and nano hardness. Statistical Analysis: Results obtained were subjected
to one way ANOVA and Turkey's post hoc test at significance (p <0.05). Results:
There was significant differences among composites restorative resins tested. CFM
Nano hybrid composite exhibited highest hardness values. Flexural strength,
flexural modulous and hardness properties of Ever X and Z350 were almost similar.
Compressive strength value of Ever X was high compared with other four
composites. SDR exhibited least values when compared with other composites.
Conclusion: Differences in compressive strength, hardness, flexural strength and
modulous is due to differences in percentage and type of filler particles in all
composite resin material tested.
PMID- 29962781
TI - Influence of Light Energy Density, Composite Type, Composite Thickness, and
Postcuring Phase on Degree of Conversion of Bulk-fill Composites.
AB - Context: Achieving a high degree of conversion (DC) is one of the major concerns
during photopolymerization of bulk-fill composites. Aims: To evaluate the effect
of light energy densities (11.2 J/cm2 and 20 J/cm2) on the DC and variation of DC
in the 24-h postcuring of four bulk-fill composites: SDR, Venus Bulk Fill, MI
FIL, and Tetric N-Ceram Bulk Fill at simulated clinically relevant filling
depths. Settings and Design: This was an in vitro comparative study. Subjects and
Methods: A total of twenty samples were prepared using a teflon mold. VALO curing
light was used with two light intensity modes of 1000 mW/cm2 for curing time of
20 s and 1400 mW/cm2 for curing time of 8 s. The energy density was calculated as
follows: energy density (J/cm2) is the light intensity (mW/cm2) applied during a
certain time (s) divided by 1000. The DC was measured at two time intervals:
immediately postcure and after 24-h storage in artificial saliva using an Fourier
transform infrared spectroscopy equipped with attenuated total reflectance
accessory. Statistical Analysis Used: ANOVA and Bonferroni test at P < 0.05.
Results: High energy density (20 J/cm2) leads to higher DC. Thickness, type of
composites, and postcuring phase strongly influence the DC. DC values of the top
surface for all the bulk-fill materials investigated were found significantly
greater (P < 0.005) than those of their bottom surface. Among composites, SDR
showed highest DC. DC strongly increased after 24-h postcure by 32% on top
surface and 76% on bottom surface. Conclusions: Energy density more than 20
J/cm2, derived by increasing curing time and low power density, helps obtain a
high DC of bulk-fill composites for adequate clinical performance.
PMID- 29962783
TI - Comparison between the Outcomes of Two Platelet-Rich Concentrates on Apexogenesis
in Young Permanent Incisors Requiring Endodontic Retreatment.
AB - Platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) have been successfully
used for inducing pulp regeneration in nonvital teeth. This case report
highlights the difference between the outcomes of using PRF and PRP for pulp
regeneration in a 13-year-old male patient, who had reported with endodontic
treatment failure in his upper incisors. Gutta-percha and sealant were removed,
and triple antibiotic paste (TAP) was placed in all the root canals and sealed
with cavit. Subsequently, after TAP removal, 11 and 12 were treated with PRF,
while 21 and 22 were treated with PRP. A resorbable matrix was placed over the
PRF/PRP, over which mineral trioxide aggregate and glass ionomer cement were
placed. After 2 years, all the upper maxillary incisors revealed dentinal wall
thickening, root lengthening, and apical closure. However, apical bridge
formation occurred only in incisors treated with PRF.
PMID- 29962782
TI - The "TROJAN HORSE" of a Dental Visit - Synovial Sarcoma.
AB - The term "synovial sarcoma (SS)" is a histological error, a misnomer as it
neither arises from nor differentiates toward synovium. Head and neck region is
the most commonly affected region after extremities, representing 5% of all
cases. This case report focuses to discuss a case of a SS that was diagnosed
after an inadvertent root canal therapy. A 46-year-old male came to the
outpatient department with a chief complaint of pain and swelling in his upper
right back tooth region since 15 days. An ulceroproliferative mass of was
observed protruding from the gingivobuccal sulcus from 11 to 15 tooth region
obliterating the vestibule.
PMID- 29962784
TI - Natural Crown Bonding of Anterior Fractured Teeth at Different Levels of
Complexity: A 14-Month Follow-up.
AB - Dental fractures comprise the most frequent form of traumatic dental injury and
often require an immediate procedure for their treatment. The repositioning of
fractured crown fragments using the bonding fragment technique offers several
advantages, including the reestablishment of function, esthetics, shape, shine,
and surface texture, in addition to the maintenance of the original contour and
alignment of the teeth. The aim of this article is to describe a therapeutic
approach used with a patient who suffered varying degrees of crown fractures in
three teeth that were treated with adhesive fragment reattachment. The natural
crown bonding technique, using tooth fragments and a direct composite resin,
successfully restored all of the fractured anterior teeth. The clinical
examinations showed good esthetics and periodontal health after a 14-month follow
up, proving that the technique is a good option for tooth fractures.
PMID- 29962785
TI - Sarcomatoid Carcinoma: A Clinicopathological Profile of Two Cases with Diagnostic
Emphasis.
AB - Sarcomatoid carcinoma (SC) is an unusual and aggressive variant of squamous cell
carcinoma, which frequently recurs and metastasizes, and is associated with poor
survival rate. For this reason, its accurate diagnosis is very important. It is
considered to be a biphasic tumor made up of epithelial as well as spindle cell
component, but of epithelial origin. The diagnosis often represents a
clinicopathologic challenge, and immunohistochemistry plays a key role in the
histopathological diagnosis. The reported cases in oral cavity are limited. Here,
we present two cases of SC where the use of immunohistochemistry allowed us to
achieve a conclusive diagnosis.
PMID- 29962787
TI - Orthognathic Surgical Approach for Management of Skeletal Class II Vertical
Malocclusion.
AB - The current era of orthodontics has evolved from regular dental corrections to
achieve the most needed harmony between functional stability and esthetics
enhancement of craniofacial structures. The "desire" for attaining this harmony
led to the birth of orthognathic surgeries. The orthognathic approach has
undergone a paradigm shift through the years, from correcting the skeletal
component to addressing the soft tissues, thus optimizing esthetic outcome. This
present case report is of a patient with skeletal Class II malocclusions with
vertical maxillary excess (VME), managed by multidisciplinary treatment approach.
The treatment progressed through presurgical orthodontics with premolar
extraction followed by bi-jaw surgery. The outcome resulted in a phenomenal
change in the profile by establishing a Class I skeletal base with a stable
occlusion.
PMID- 29962786
TI - Endodontic Management of Curved Canals with ProTaper Next: A Case Series.
AB - The curved and dilacerated roots in the posterior teeth often present the major
challenge to the clinicians during the endodontic treatments. The efficient
biomechanical preparation is also affected by improper instrumentation in the
curved or the constricted canals. The use of conventional instruments and
techniques in the dilacerated roots may develop ledges, fractured instruments,
and canal blockages which further complicate the endodontic treatments. The
introduction of ProTaper Universal rotary instruments has made a significant
impact in the biomechanical preparation of root canals systems. However, the
fracture rate of these files and inconvenience to treat the posterior teeth in
reduced mouth opening conditions limits their successful usage in endodontic
treatments. The ProTaper Next rotary instruments have noted advantages such as
increased flexibility, higher strength, and wear resistance over the conventional
rotary endodontic systems. The current case series discusses the endodontic
treatment of three severely curved root canal systems successfully treated with
ProTaper Next rotary endodontic system.
PMID- 29962788
TI - Impacted Primary Mandibular Second Molar Associated with Late-Formed Second
Premolar: A Rare Entity of Reverse Dentition.
AB - Impaction of the tooth in primary dentition is very less common than the
permanent dentition. Impaction of teeth in primary dentition may create various
problems in occlusion and also in developing dentition. Clinical and radiographic
evaluation of such cases may benefit the patient as well as the clinician. Among
primary tooth impaction cases, second primary molars are not frequently reported
along with late formation of its succedaneous tooth. Nevertheless, the purpose of
this report was to describe a case of a rare entity of reverse dentition caused
by the impaction of the mandibular primary second molar associated with delayed
formation of the second premolar.
PMID- 29962789
TI - Endodontic Management of Mandibular Second Premolar with Type IX Canal
Configuration Using Cone-Beam Computed Tomography as a Diagnostic Aid: A Rare
Case Report.
AB - Successful endodontic treatment requires knowledge of the root canal anatomy,
cleaning, and shaping followed by three-dimensional filling of the root canals.
With the advent of newer diagnostic aids such as cone-beam computed tomography
(CBCT) and magnifying tools such as dental operating microscope and loupes, it
has become easier for an operator to identify the root canal anatomy of teeth and
reduce the risk of procedural accidents and failures. Variations in root canal
configuration require modification in access cavity preparation, disinfection,
and obturation of the canals. Mandibular premolars are identified to have unusual
root and canal anatomy which increases the risk of endodontic failure when
additional canals remain undiagnosed. The present case report elaborates
successful endodontic management of a mandibular second premolar with Type IX
root canal configuration using CBCT as a diagnostic tool.
PMID- 29962790
TI - Unique Denture Identification System for All Indian Nationals.
AB - Marking dental prosthesis has always been considered an important part of
forensic dentistry. Denture identification systems are important not only for
patients in health-care facilities, old-age homes, and hospitals but also in
medico-legal cases. In India, no standardized method is being followed for
labeling of the dentures. This article proposes a technique of denture marking
that gives permanent, unique, and global identification to all the Indian
nationals using Aadhaar - a universally accepted identity for Indian nationals.
The information on the card can be printed on a piece of paper or a plastic card
and the Aadhaar card quick read code/number can be easily and cost-effectively
used for marking all the newly constructed or existing prosthetic devices.
PMID- 29962791
TI - Prosthodontic Rehabilitation for a Worn Out Dentition Using Aesthetic
Preevaluative Temporaries and Dental GPS Smile Designing Concepts: A Clinical
Report.
AB - : An optimally created occlusion will be better able to deal with the forces
generated in function and parafunction. This case report will highlight the full
mouth rehabilitation of a patient with worn out dentition in the minimally
invasive way which offers the users a more systematic and a precise treatment.
CLINICAL RELEVANCE: It gives us an idea of a treatment modality for full-mouth
rehabilitation whereby the anterior teeth cause a uniform disocclusion of the
posterior teeth during excursive movements, thereby protecting the teeth from the
harmful effects of the cuspal interference.
PMID- 29962792
TI - Polycystic Ovarian Syndrome-Related Depression in Adolescent Girls: A Review.
AB - Polycystic ovarian syndrome (PCOS), a common endocrinal disorder of reproductive
age characterized by heterogeneous complications, is nowadays prevailing among
females at adolescent stage. Infrequent or prolonged menstrual periods, excess
hair growth, acne, and obesity can occur in women with PCOS. In adolescents,
infrequent or absence of menstruation may raise chances for this condition. The
increased prevalence of PCOS among general population throughout the world is
found to be 5%-10% in the women of reproductive age, and about 40% women with
PCOS experience depression, particularly young girls. The exact cause of PCOS is
unknown. Early diagnosis and treatment along with weight loss may reduce the risk
of long-term complications. Depression and anxiety are common in women with PCOS
but are often overlooked and therefore left untreated. Along with the physical
disturbances, many mental problems are also associated with PCOS. Therefore, PCOS
not only has problems associated with reproduction but also has associated
crucial metabolic and psychological health risks with increasing age of the
patients. Because of the increased number of cases with PCOS around the world in
present times, with prominent symptom of, specifically, depression at the
adolescent stage, it is important to highlight the disease.
PMID- 29962793
TI - Electrochemical Oxidability of Antioxidants: Synergism and Antagonism in Mixes.
AB - Aims: To investigate electrochemical oxidability of antioxidants to reveal
synergistic and antagonistic effects in mixes. Materials and Methods:
Electrochemical oxidability of some widely used antioxidants, including uric
acid, glutathione, trolox, ascorbic acid, gallic acid, Mexidol, and potassium
fenozan, was investigated by the amperometric approach. Results: All obtained
electrochemical oxidability values correlate well with antioxidant activity
parameters of the same compounds measured by other methods. The measurements of
the electrochemical oxidability for binary mixes of substances were tested to
reveal any synergistic actions. The experimental results and calculated values
overlap for various combinations of tested mixes. It testifies to the absence of
interaction between them (both synergism and antagonism) in the oxidation
process. Conclusions: The constants of oxidation were defined for different
antioxidants and mixes by amperometric approach. Most mixes of probed compounds
revealed absence of interaction between them in oxidation process. In some cases
(mainly with glutathione and ascorbic acid), antagonism takes place,
deteriorating effects of their joint application. Apparently, a partial reduction
of glutathione by ascorbic acid leads to excess of the measured value over
calculated value.
PMID- 29962794
TI - Protective Effect of Rheum turkestanicum against Cisplatin by Reducing Oxidative
Stress in Kidney Tissue.
AB - Background: Cisplatin is used as chemotherapeutic drug in the treatment of some
solid tumors. It causes different side effects such as nephrotoxicity because of
increasing oxidative stress and reactive oxygen species production. This study
was designed to investigate the effect of Rheum turkestanicum on cisplatin
induced nephrotoxicity in rat. Materials and Methods: Animals were randomly
divided into four groups (six each). Group I received normal saline (1mL/day,
intraperitoneally [i.p.]). Group II received a single dose of cisplatin (8mg/kg,
i.p.). Groups III and IV received extract at doses of 100mg/kg and 200mg/kg,
i.p., respectively, for 3 consecutive days, 1h before a single dose of cisplatin
only at the first day. Blood samples were taken for measuring the level of urea
and creatinine. Furthermore, 24-h urinary factors such as glucose and protein
were measured. Histopathological observation was carried out on kidney sections.
Statistical analysis was performed using one-way analysis of variance followed by
Tukey-Kramer post hoc test for multiple comparisons. Results: Cisplatin increased
the lipid peroxidation, serum creatinine, serum urea, urinary glucose, and
urinary protein, whereas decreased the content of thiol in kidney. The extract
reduced serum creatinine, serum urea, urinary glucose, urinary protein, lipid
peroxidation, and increased thiol following cisplatin administration.
Histological studies revealed lower lesions in kidney in the extract-treated
groups compared to cisplatin-treated one. Conclusion: This research showed the
extract has protective effect against cisplatin-induced nephrotoxicity. This
observation may be related to antioxidant properties of the extract.
PMID- 29962795
TI - Pharmacoepidemiological Observational Study of Antimicrobial Use in Outpatients
of Ophthalmology Department in North Indian Population.
AB - Background: Recognition of drug usage patterns provides the basis for improving
safety and plummeting risks associated with their use. Thus, this study was
undertaken to explore the drug usage pattern in ophthalmology with an emphasis on
antimicrobial use at a tertiary care teaching hospital. Materials and Methods: An
observational study was conducted in the Department of Ophthalmology, Hakeem
Abdul Hameed Centenary Hospital, Jamia Hamdard, New Delhi, India for 9 months.
Newly registered patients visiting the Outpatient Department for curative
complaints were included. All drugs prescribed were recorded, including dose,
route, dosage form, frequency of administration, indications for prescription,
and duration of therapy, and the data was audited using the indicators prescribed
by the World Health Organization. Result: A total of 600 prescriptions were
analyzed. The number of drugs prescribed was 1097 with an average drug per
prescription being 1.8. The most common disorders diagnosed were infective
conjunctivitis (21.5%) followed by stye (5.5%). Drugs were prescribed in
different dosage forms with eye drops (72.6%) being the most common. Drugs were
predominantly prescribed by brand name (100%). Antimicrobials (44.7%) were the
most commonly prescribed drugs followed by lubricants (17.5%). Moxifloxacin
(53.5%) was the most commonly prescribed antimicrobial agent. Of the
antimicrobials prescribed, 89.6% were prescribed topically. Average total cost
per prescription was 113 INR. Conclusion: The study concludes with an overall
impression of rational prescription in terms of prescribing in consensus with the
recommended treatment protocol of ocular diseases. Nevertheless, health-care
professionals should be encouraged to prescribe by generic name. Creating
awareness regarding selection of drugs from essential drug list to reduce the
drug cost is the need of the hour. Last but not least, updating knowledge
regarding appropriate antimicrobial use and the development of discreet
strategies for their use should be implemented to steer clear of antimicrobial
resistance.
PMID- 29962796
TI - Assessment of Knowledge, Attitude, and Practice of Dental and Medical Interns
toward Toothbrush Maintenance and Replacement in Bhubaneswar City, Odisha, India.
AB - Background: Toothbrushes are an important medium for maintaining good oral
hygiene, and hence there arises a need to maintain and replace toothbrushes at a
regular interval. Assessing the knowledge, attitude, and practice (KAP) of the
medical and dental interns would help the society in promoting oral hygiene in a
broader aspect. Materials and Methods: A cross-sectional questionnaire study was
conducted among 759 medical and dental interns residing in Bhubaneswar, Odisha,
India. The data on oral health KAP were collected using a self-structured
questionnaire. Descriptive statistics was evaluated using SPSS software package,
version 19. Results: Of 759 participants, 445 were dental interns and 314 were
medical interns. Knowledge about toothbrush maintenance was seen to be more in
the dental interns. The attitude toward maintenance was seen to be better among
the dental interns compared with the medical interns. The practice of toothbrush
maintenance was seen in both the groups but more dominantly in the dental
interns. Conclusion: Education regarding the effective use and maintenance of the
toothbrush would help improve the KAP toward toothbrush maintenance and
replacement. The lack of knowledge holds back the attitude of properly
maintaining the toothbrush in a regular basis.
PMID- 29962798
TI - Adverse Drug Reactions Attributed to Fondaparinux and Unfractionated Heparin in
Cardiovascular Care Unit: An Observational Prospective Pilot Study in a Tertiary
Care Hospital.
AB - Introduction: This study was carried out to collect and analyze the adverse drug
reactions (ADRs) reported with use of anticoagulants, heparin and fondaparinux.
These drugs are vital in the treatment of unstable coronary artery diseases and
emergencies. Materials and Methods: A cross-sectional study with active reporting
of ADRs from cardiology and medicine department was conducted. The type of
reaction was assessed by Rawlins and Thomson criteria, causality by Naranjo
probability scale, severity by modified Hartwig criteria, and preventability by
Schumock and Thornton criteria. Result: Of the 67 patients observed, 16 showed
ADRs. Fifteen reactions were attributable to unfractionated heparin and one to
fondaparinux following assessment by the Naranjo causality scale. Severity of the
ADRs assessed by modified Hartwig criteria showed that although 12 of 16 (75%)
were mild, 4 (25%) were moderate in severity. Modified Schumock and Thornton
criteria showed that 9 of 16 (56.25%) reactions could not have been prevented
whereas 5 (31.25%) were probably preventable and 2 (12.5%) were definitely
preventable. Conclusion: Incidence of ADRs with fondaparinux was lower than with
heparin, hence emphasizing its better safety profile. The study also highlights
the need for nurses and other caretakers in the coronary care unit to enquire for
and report ADRs, particularly with high-potency medicines that are associated
with an equally high potential to induce ADRs.
PMID- 29962797
TI - In Vitro Antilithiatic Potential of Kalanchoe pinnata, Emblica officinalis,
Bambusa nutans, and Cynodon dactylon.
AB - Objective: The study aims at the exploration of calcium oxalate (CaOx) crystal
growth inhibition potential of Cynodon dactylon, Emblica officinalis, Kalanchoe
pinnata, and Bambusa nutans ethyl acetate fraction rich in polyphenol and
flavonoid. Materials and Methods: Ethyl acetate fraction was separated from the
hydromethanolic extract of C. dactylon, E. officinalis, K. pinnata, and B. nutans
followed by quantitative analysis for total polyphenol and flavonoid content.
Ethyl acetate fraction of all the plants were subjected to in vitro screening for
the inhibition of CaO x crystals growth induced by sodium oxalate. Results: The
results signify rich presence of polyphenols and flavonoids in K. pinnata and E.
officinalis ethyl acetate fractions followed by C. dactylon and B. nutans. Ethyl
acetate fractions of B. nutans shoot, E. officinalis fruit, and K. pinnata leaf
have excellent in vitro CaO x crystal growth inhibition potential based on both
the comparative concentration and the time level to achieve IC50. Conclusion: The
study outcome substantiates potential in vitro CaO x crystal dissolution and
crystal growth inhibition properties of E. officinalis, B. nutans, C. dactylon,
and K. pinnata. Rich presence of caffeic acid, ferulic acid, and luteolin in
ethyl acetate fraction of B. nutans leaf, and chebulinic acid, chebulagic acid,
gallic acid, ellagic acid, and quercetin of E. officinalis may have produced
prominent crystal aggregation inhibition response.
PMID- 29962799
TI - Emerging Biocide Resistance among Multidrug-Resistant Bacteria: Myth or Reality?
A Pilot Study.
AB - Context: Possible linkage between biocide and antibiotic resistance in bacteria
is a major area of concern. Aim: To evaluate the susceptibility of multidrug
resistant (MDR) bacteria to four commonly used biocides. Settings and Design: A
pilot study was conducted in a tertiary care hospital from April to November
2017. Materials and Methods: Fifty-four MDR bacterial isolates, namely
Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and
Staphylococcus aureus, were obtained from various clinical samples of inpatients.
These isolates were subjected to tube dilution method for determining minimum
inhibitory concentration (MIC) of four commonly used biocides in our hospital,
namely 5% w/v povidone iodine, absolute ethanol (99.9%), sodium hypochlorite (4%
available chlorine), and quaternary ammonium compounds (QACs) (3.39%). Minimum
bactericidal concentration (MBC) of these biocides was determined as per standard
guidelines. Similar tests were also performed on corresponding American Type
Culture Collection (ATCC) bacterial strains. Statistical Analysis: The Fisher
exact test. Results: Twenty-two MDR bacterial isolates had higher MIC values for
QACs than their corresponding ATCC strains. Statistically significant difference
in proportion of test isolates exhibiting higher MIC values for QACs and absolute
ethanol was observed (P-value = 0.02). Twenty-four MDR bacterial isolates
exhibited higher MBC values for sodium hypochlorite than their corresponding ATCC
strains. The difference in proportion of test isolates exhibiting higher MBC
values for sodium hypochlorite and absolute ethanol, respectively, was
statistically significant (P-value <0.0001). The difference in proportion of test
isolates exhibiting higher MBC values for absolute ethanol versus QACs and
povidone iodine, respectively, was statistically significant (P-values = 0.0003
and 0.0076). Statistically significant differences in susceptibility to biocides
among test isolates were also observed. Conclusion: Emergence of biocide
resistance among MDR bacteria poses a serious threat to our efforts in containing
outbreaks of nosocomial infections.
PMID- 29962800
TI - Eosinophilia in Advanced HIV Infection with Hyperinfection Syndrome: A Case
Report.
AB - Strongyloides stercoralis is a soil-transmitted helminth that occurs almost
worldwide, yet estimates about its prevalence are not well documented. The
spectrum of clinical manifestations of strongyloidiasis is wide, ranging from
asymptomatic disease to hyperinfection or dissemination of larvae involving
multiple organ systems. Immunosuppression can increase the risk of hyperinfection
syndrome in patients with strongyloidiasis. Strongyloidiasis continues to remain
a neglected tropical disease, the diagnosis of which is often overlooked by
clinicians and diagnosticians alike. The paucity of published literature from
India further accentuates this problem. We hereby present a case report with the
aim of elucidating this relatively underreported infection.
PMID- 29962801
TI - Lab on a Chip: Conquer Disease at the Earliest.
AB - Oral cancer is the fifth most common cancer in the world, accounting for numerous
deaths annually. The 5-year survival rate remains approximately 50% for oral
squamous cell carcinoma (OSCC) in the past several decades. Early detection plays
a vital role in the survival rate of the patients. There is no accurate, cost
effective, and reliable method for the screening of patients with OSCC. Hence,
many patients are diagnosed at advanced stages. Early detection would, therefore,
help to identify patients and modify treatment with close monitoring. Lab on a
Chip or micro-total-analysis systems are one of the microfluidics technologies
that are defined as adaptation, miniaturization, integration, and automation of
analytical laboratory procedures into a single device or "chip." This technology
assures the replacement of complicated techniques with miniaturized, integrated,
programmed, and economical diagnostic devices. Hence, this system provides a
means for rapid, automated, molecular analysis of cancer cells.
PMID- 29962802
TI - Hot Flashes-How Long ??
PMID- 29962803
TI - Clinical Evaluation of Urinary Incontinence.
AB - Pelvic organ prolapse is the downward descent of the pelvic floor organs and has
a prevalence of 3%-6% and can even reach to 50% if defined by a vaginal
examination. The anatomical concepts of pelvic diaphragm, lateral attachment of
vagina to arcus tendineus fascia pelvis, and intrinsic and extrinsic sphincter
control mechanisms are elaborated. The anatomic and physiological mechanisms of
autonomic and voluntary control of continence are discussed. The clinical and
urodynamic tests and their implications in guiding the management are explained.
Finally, uroflowmetry, cystometry, urethral pressure profile, postvoid urine
measurement, leak point pressure (LPP) test, video urodynamic tests, and
electromyography studies of pelvic floor are discussed as an integral part of the
assessment.
PMID- 29962804
TI - Mifepristone Therapy in Symptomatic Leiomyomata Using a Variable Dose Pattern
with a Favourable Outcome.
AB - Background: Leiomyomata causing symptoms have a deleterious effect on the health
of women during reproductive age. Mifepristone, a progesterone antagonist was
studied for reduction of symptoms in leiomyomata in perimenopausal women.
Material and Methods: Mifepristone was adminstered to 7 women aged 47-50 years.
Another 3 women less than 47 years were taken up for comparison of benefit of
Mifepristone on leiomyomata related symptoms. Mifepristone was given in a
stepwise declining dose for a period of 9 months to 1 year . The treatment was
begun with 25 mg and the dose was reduced every 3 months. Every 3 months, the
size of myomas, bleeding pattern, location of myomas, endometrial thickness,
haemoglobin, and any side effects were all recorded. Results: There was
considerable amelioration in the symptoms in both premenopausal as well as
perimenopausal women, while mifepristone was continued. The reduction in myoma
size was found to be statistically significant. After stoppage of drug in women
aged 40-45 years, i.e. premenopausal group, the symptoms returned. However, in
perimenopausal women, in 6 out of 7 women the symtoms abated completely and they
had a smooth transition to menopause. Conclusion: Mifepristone is a very
promising drug for conservative management of leiomyomata, especially in
perimenopausal age (47years or more), where hysterectomy was averted in all 7
women.
PMID- 29962805
TI - Dietary Intake, Prevalence, and the Effect of Anemia on Various
Morphophysiological Variables of Postmenopausal Women of North India.
AB - Context: Anemia has a high prevalence among postmenopausal Indian females. Aim
and Objective: The aim of this study was to evaluate dietary intake, prevalence,
and the effect of anemia on various morphophysiological variables among
postmenopausal women. Setting and Design: This was a community-based sample
survey. Materials and Methods: A total of 250 postmenopausal women aged 45-80
years from various parts of North India participated in the study. Anthropometric
measurements, hemoglobin concentration, and bone mineral density (BMD) (using
dual-energy X-ray absorptiometry) of each participant were assessed. A 24-h
dietary recall method for three consecutive days was employed. Statistical
Analysis: The Statistical Package for the Social Sciences version 20 was used for
statistical considerations. Results: An age-associated decline in the mean values
of hemoglobin concentration and the prevalence of anemia was reported to be 85.2%
among postmenopausal women. Anemic women were lighter and had lesser
circumferential measurements as well as lower BMD than their nonanemic
counterparts. The intake of nutrients such as protein, calcium, and iron and
energy was lower among anemic women than nonanemic women. Binary logistic
regression analysis identified age (odds ratio = 1.04, 95% confidence interval =
1.00-1.09)* as the possible predictor of anemia. Conclusions: Anemia was not only
the result of aging process but also inadequate and unbalanced dietary intake.
PMID- 29962806
TI - Obesity and its Effects on Health in Middle-Aged Women from Slums of Pune.
AB - Aim: The study aims to find out the prevalence of obesity and its consequences on
the health of middle-aged (45-59 years) women in slum areas. Methodology: The
present study includes 559 women between 45 and 59 years of age from slums of
Pune city, Maharashtra. Data were collected using a structured questionnaire,
anthropometric measurements, physical activity using International Physical
Activity Questionnaire long version, information on dietary habits, chronic
illnesses, etc., Univariate analysis and further multiple logistic regressions
were used to determine associations and risk estimates using Statistical Package
for the Social Science version 16. Results: About 60% had body mass index (BMI)
above normal, 39% were overweight, and 21.3% obese. The percentage of obesity
increased with increasing age. Obesity was significantly associated with working
status (P = 0.042), hypertension (P = 0.013), knee pain (P = 0.029), squatting (P
= 0.001), walking (P = 0.001), climbing stairs (P = 0.004), and rising from chair
(P = 0.040). Functional decline was reported by 62.8% women. Odds of having high
blood pressure 1.8 (95% confidence interval [CI]: 1.1-3.0), difficulty in
squatting, walking was 1.5 (95% CI: 1.0-2.4) and 1.9 (95% CI: 1.0-3.6)
respectively more in overweight. Higher odds of having blood pressure 1.8 (95%
CI: 1.0-3.3) and difficulty in walking 2.4 (95% CI: 1.2-4.6) was observed in
obese women as compared to women in normal BMI category. Conclusion: The study
shows that the prevalence of obesity is higher among women even in the low-income
areas. This indicates a need for specific interventions targeted to women in
urban slum. The inclusion of multicomponent intervention will prove to be
beneficial at the community level.
PMID- 29962807
TI - Association of Dyslipidemia, Increased Insulin Resistance, and Serum CA 15-3 with
Increased Risk of Breast Cancer in Urban Areas of North and Central India.
AB - Objective: This study aims to determine the association of dyslipidemia and
increased insulin resistance (IR) with increased breast cancer (BC) risk.
Materials and Methods: The study group comprised 110 premenopausal and 143
postmenopausal, untreated female BC patients in the age range of 29-72 years.
Control group consisted of 117 premenopausal and 141 postmenopausal healthy
females in the age range of 23-75. Approximately 8-ml blood samples were drawn to
measure various biochemical parameters. Serum glucose, total cholesterol,
triglyceride (TG), and high-density lipoprotein-cholesterol were measured. Very
low-density lipoprotein-cholesterol (VLDL-C) and LDL-C were calculated using
Friedewald's formula. Serum insulin and serum CA 15-3 were estimated by immune
enzymatic assay. IR was assessed using homeostasis model assessment IR index
(HOMA-IR). Results: Clinical variables in the case and control groups were
compared using the unpaired Student's t-test. The crude and adjusted odds ratios
(ORs) and 95% confidence intervals (CIs) were calculated by binary logistic
regression analysis. Pearson's correlation analysis was used to determine the
association between CA 15-3 and variables of interest. Total cholesterol, TG,
LDL, VLDL, serum glucose, serum insulin, HOMA-IR, and serum CA 15-3 were
significantly higher (P < 0.001) in BC patients compared to those in controls.
Significant adjusted ORs with 95% CI were found to be fasting glucose, total
cholesterol, and TGs. We also found a significant positive correlation between
total cholesterol, TG, LDL, serum glucose, serum insulin, HOMA-IR, and serum CA
15-3. Conclusion: This study confirms the association between dyslipidemia, IR,
and increased BC risk.
PMID- 29962808
TI - Iron Deficiency Anemia with Menorrhagia: Ferric Carboxymaltose a Safer
Alternative to Blood Transfusion.
AB - Background: Menstrual disorder accounts for 5%-10% of the women presenting with
iron deficiency anemia (IDA) in the perimenopausal age group. Heavy menstrual
bleeding in this age group leads to severe anemia and frequently requires blood
transfusion which has its own adverse effects. We today have ferric
carboxymaltose (FCM) as a safer alternative to blood transfusion. Objective: The
objective of the study is to evaluate the safety and efficacy of FCM in treating
anemia in patients of menorrhagia. Thus avoiding blood transfusion. Materials and
Methods: It was an open, single arm observational study including 90 women of age
more than 30 years with definitive diagnosis of menorrhagia with IDA and
hemoglobin (Hb) levels between 4 gm% and 11 gm%. Intravenous FCM (500-1500 mg)
was administered, and the improvement in blood indices was assessed after 3 weeks
of total dose infusion. Menorrhagia was controlled by medical treatment till Hb
improvement was achieved and definitive surgical intervention was done. Result:
Most of the women were in the age group of 40-50 years. Blood indices measured
pre-FCM and 3 weeks post-FCM showed a mean increase in Hb from 8.33 +/- 1.10 to
10.89 +/- 1.02 with a statistically significant P < 0.01. There was a
statistically significant rise of packed cell volume, serum ferritin, and serum
iron in the post-FCM blood levels after 3 weeks. No serious life-threatening
adverse events were observed after FCM administration. Conclusion: Intravenous
FCM is an effective and a safe treatment option for IDA with a single
administration of high dose without serious adverse effects obviating the need
for blood transfusion before surgery.
PMID- 29962809
TI - Polypharmacy among the Elderly.
AB - Introduction: Older people are at risk for polypharmacy due to multiple chronic
diseases. Considering the lack of information in this regard, the aim of this
study was to investigate the state of polypharmacy among the elderly in the city
of Amirkola in northern part of Iran. Materials and Methods: This
descriptive/analytical cross-sectional study is a part of Amirkola Health and
Aging Project that was conducted on 1616 individuals aged 60 years and over. The
data about medications were gathered through interviews and observation of
prescriptions and medications consumed by patients. The data were analyzed by
SPSS software version 18, and P <= 0.05 was regarded significant. Results: In
this study, 1616 individuals including 883 men (54.6%) and 733 women (45.3%) were
investigated. The average age of individuals was 69.37 +/- 7.42. Among the
investigated individuals, 526 including 368 men (41.7%) and 158 women (21.6%)
consumed no medications. The prevalence of polypharmacy in this study was 23.1%,
which was 32.7% in women and 15.2% in men (odds ratio = 1.51, 95% confidence
interval: 1.10-1.93). The most prevalent group of medications used in both
genders was cardiovascular drugs. Conclusions: Regarding the considerable
prevalence of polypharmacy among the elderly, especially in aged women, serious
efforts are required to manage polypharmacy. Provision of educational programs
for physicians, personnel of pharmacies, and the staff of health-care centers in
order for appropriate and safe consumption of medications in aged people is
absolutely necessary.
PMID- 29962810
TI - Pseudocarcinomatous Hyperplasia of the Fallopian Tube Mimicking a Tubal Neoplasm:
A Rare Entity.
AB - Pseudocarcinomatous hyperplasia of the fallopian tube is a rare, reactive
response to an underlying inflammatory or neoplastic process. Only a few cases
have been reported in literature. It is a benign condition that mimics a
malignant neoplasm clinically and radiologically. Thus, a preoperative diagnosis
of this entity is important to avoid radical surgical treatment. We report a case
of pseudocarcinomatous hyperplasia of the fallopian tube in a 27-year-old female,
which was clinically and radiologically thought to be a tubal neoplasm. The
approach to such a case and the differentiating features from adenocarcinoma have
also been discussed.
PMID- 29962811
TI - Methimazole-Induced Neutropenic Gingival Ulcerations and Necrosis in a Middle
Aged Female: A Case Report with Clinical Management.
AB - One of the major manifestations of methimazole-induced neutropenia or
agranulocytosis is diffuse gingival ulceration and necrosis. The aim of this case
report is to be familiar with drug-induced neutropenia and its associated oral
manifestations and the healing of the gingiva after proper treatment.
PMID- 29962812
TI - Glycoprotein biomarkers for the detection of pancreatic ductal adenocarcinoma.
AB - Pancreatic cancer (PaC) shows a clear tendency to increase in the next years and
therefore represents an important health and social challenge. Currently, there
is an important need to find biomarkers for PaC early detection because the
existing ones are not useful for that purpose. Recent studies have indicated that
there is a large window of time for PaC early detection, which opens the
possibility to find early biomarkers that could greatly improve the dismal
prognosis of this tumor. The present manuscript reviews the state of the art of
the existing PaC biomarkers. It focuses on the anomalous glycosylation process
and its role in PaC. Glycan structures of glycoconjugates such as glycoproteins
are modified in tumors and these modifications can be detected in biological
fluids of the cancer patients. Several studies have found serum glycoproteins
with altered glycan chains in PaC patients, but they have not shown enough
specificity for PaC. To find more specific cancer glycoproteins we propose to
analyze the glycan moieties of a battery of glycoproteins that have been reported
to increase in PaC tissues and that can also be found in serum. The combination
of these new candidate glycoproteins with their aberrant glycosylation together
with the existing biomarkers could result in a panel, which would expect to give
better results as a new tool for early diagnosis of PaC and to monitor the
disease.
PMID- 29962814
TI - Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating
cell.
AB - Gastric cancer (GC) remains one of the most common and malignant types of cancer
due to its rapid progression, distant metastasis, and resistance to conventional
chemotherapy, although efforts have been made to understand the underlying
mechanism of this resistance and to improve clinical outcome. It is well
recognized that tumor heterogeneity, a fundamental feature of malignancy, plays
an essential role in the cancer development and chemoresistance. The model of
tumor-initiating cell (TIC) has been proposed to explain the genetic,
histological, and phenotypical heterogeneity of GC. TIC accounts for a minor
subpopulation of tumor cells with key characteristics including high
tumorigenicity, maintenance of self-renewal potential, giving rise to both
tumorigenic and non-tumorigenic cancer cells, and resistance to chemotherapy.
Regarding tumor-initiating cell of GC (GATIC), substantial studies have been
performed to (1) identify the putative specific cell markers for purification and
functional validation of GATICs; (2) trace the origin of GATICs; and (3) decode
the regulatory mechanism of GATICs. Furthermore, recent studies demonstrate the
plasticity of GATIC and the interaction between GATIC and its surrounding factors
(TIC niche or tumor microenvironment). All these investigations pave the way for
the development of GATIC-targeted therapy, which is in the phase of preclinical
studies and clinical trials. Here, we interpret the heterogeneity of GC from the
perspectives of TIC by reviewing the above-mentioned fundamental and clinical
studies of GATICs. Problems encountered during the GATIC investigations and the
potential solutions are also discussed.
PMID- 29962813
TI - Hepatitis C virus infection in children in the era of direct-acting antiviral.
AB - Hepatitis C virus (HCV) infection remains an important global health problem with
chronic infection affecting approximately 11 million children worldwide. The
emergence of direct-acting antiviral (DAA) therapies and the development of non
invasive methods for the determination of liver fibrosis will significantly
improve the management of paediatric patients with chronic HCV infection in
subsequent years. For paediatric patients, a new era of highly effective DAA
agents is beginning, and the first results of available clinical trials are very
promising. In this era, the identification and monitoring of patients continues
to be an important issue. The availability of non-invasive serological and
imaging methods to measure hepatic fibrosis enables the identification of
patients with significant or advanced liver fibrosis stages. This article
summarizes the current data on the epidemiology and progress of research aimed to
evaluate the new therapies and non-invasive methods for liver injury in
paediatric patients with chronic hepatitis C.
PMID- 29962815
TI - Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A
few lights and many shadows.
AB - With the introduction of direct-acting antiviral agents (DAA), the rate of
sustained virological response (SVR) in the treatment of hepatitis C virus (HCV)
has radically improved to over 95%. Robust scientific evidence supports a
beneficial role of SVR after interferon therapy in the progression of cirrhosis,
resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a
debate on the impact of DAAs on the development of HCC is ongoing. This review
aimed to analyse the scientific literature regarding the risk of HCC in terms of
its recurrence and occurrence after the use of DAAs to eradicate HCV infection.
Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from
0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence,
the rate ranged from 0 to 54.4% (maximum "not well-defined" follow-up: 32 mo).
This review highlights the major difficulties in interpreting data and
reconciling the results of the included studies. These difficulties include
heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy,
the absence of an adequate control group, short follow-up times and different
kinds of follow-up. Moreover, no clinical feature-based scoring system accounts
for the molecular characteristics and pathobiology of the tumours. Nonetheless,
this review does not suggest that there is a higher rate of de novo HCC
occurrence or recurrence after DAA therapy in patients with previous HCV
infection.
PMID- 29962816
TI - Novel serum microRNAs panel on the diagnostic and prognostic implications of
hepatocellular carcinoma.
AB - AIM: To determine a panel of serum microRNAs (miRNAs) that could be used as novel
biomarkers for diagnosis of hepatocellular carcinoma (HCC). METHODS: We initially
screened 9 out of 754 serum miRNAs by TaqMan Low Density Array in two pooled
samples respectively from 35 HCC and 35 normal controls, and then validated
individually by RT-qPCR in another 114 patients and 114 controls arranged in two
phases. The changes of the selected miRNAs after operation and their prognostic
value were examined. RESULTS: miR-375, miR-10a, miR-122 and miR-423 were found to
be significantly higher in HCC than in controls (P < 0.0001), and the area under
the receiver-operating-characteristic curve for the 4-miRNA panel was 0.995
(95%CI: 0.985-1). All the four miRNAs were significantly reduced after surgical
removal of the tumors (P < 0.0001), while still higher than normal controls (at
least P < 0.05). CONCLUSION: The four serum miRNAs (miR-375, miR-10a, miR-122 and
miR-423) could potentially serve as novel biomarkers for the diagnostic and
prognostic of HCC.
PMID- 29962817
TI - Bioinformatics analysis of aberrantly methylated-differentially expressed genes
and pathways in hepatocellular carcinoma.
AB - AIM: To discover methylated-differentially expressed genes (MDEGs) in
hepatocellular carcinoma (HCC) and to explore relevant hub genes and potential
pathways. METHODS: The data of expression profiling GSE25097 and methylation
profiling GSE57956 were gained from GEO Datasets. We analyzed the differentially
methylated genes and differentially expressed genes online using GEO2R.
Functional and enrichment analyses of MDEGs were conducted using the DAVID
database. A protein-protein interaction (PPI) network was performed by STRING and
then visualized in Cytoscape. Hub genes were ranked by cytoHubba, and a module
analysis of the PPI network was conducted by MCODE in Cytoscape software.
RESULTS: In total, we categorized 266 genes as hypermethylated, lowly expressed
genes (Hyper-LGs) referring to endogenous and hormone stimulus, cell surface
receptor linked signal transduction and behavior. In addition, 161 genes were
labelled as hypomethylated, highly expressed genes (Hypo-HGs) referring to DNA
replication and metabolic process, cell cycle and division. Pathway analysis
illustrated that Hyper-LGs were enriched in cancer, Wnt, and chemokine signalling
pathways, while Hypo-HGs were related to cell cycle and steroid hormone
biosynthesis pathways. Based on PPI networks, PTGS2, PIK3CD, CXCL1, ESR1, and
MMP2 were identified as hub genes for Hyper-LGs, and CDC45, DTL, AURKB, CDKN3,
MCM2, and MCM10 were hub genes for Hypo-HGs by combining six ranked methods of
cytoHubba. CONCLUSION: In the study, we disclose numerous novel genetic and
epigenetic regulations and offer a vital molecular groundwork to understand the
pathogenesis of HCC. Hub genes, including PTGS2, PIK3CD, CXCL1, ESR1, MMP2,
CDC45, DTL, AURKB, CDKN3, MCM2, and MCM10, can be used as biomarkers based on
aberrant methylation for the accurate diagnosis and treatment of HCC.
PMID- 29962818
TI - Mediterranean dietary components are inversely associated with advanced
colorectal polyps: A case-control study.
AB - AIM: To evaluate the association between the Mediterranean diet (MD) pattern and
its components, and advanced colorectal polyps (adenoma and serrated adenoma).
METHODS: A case-control study among patients undergoing screening, diagnostic or
surveillance colonoscopies during 2010-2015 at the Tel-Aviv Medical Center,
Gastroenterology Department. Cases with advanced polyps were defined as: Advanced
adenoma [> 10 mm, with features of high grade dysplasia (HGD) or villous
histology], advanced serrated adenoma (> 10 mm or with dysplasia) or multiple (>=
3) non-advanced adenomas or serrated adenomas. Cases of non-advanced adenomas
were defined as adenomas < 10 mm, without features of HGD or villous histology.
Controls were defined as those without polyps at the current colonoscopy and
without a history of colorectal polyps. Data collection included: anthropometrics
measured according to a standardized protocol, fasting blood tests performed at
the same lab, medical history recorded by a structured interview and dietary
intake evaluated by a 116-item food frequency questionnaire. Adherence to the MD
components was evaluated according to intake above/below the sample median, for
potentially beneficial/detrimental components respectively, as accepted. RESULTS:
We recruited 206 cases with advanced polyps, 192 cases with non-advanced adenoma
and 385 controls. The number of adhered MD components was inversely associated
with a diagnosis of advanced polyps in a dose-response manner (OR = 0.34, 95%CI:
0.17-0.65; OR = 0.22, 95%CI: 0.11-0.43; and OR = 0.18, 95%CI: 0.07-0.47 for 3-4,
5-7 and 8-10 components, respectively), but not with non-advanced adenomas (OR =
0.54, 95%CI: 0.25-1.13; OR = 0.48, 95%CI: 0.23-0.99; and OR = 0.43, 95%CI: 0.16
1.12 for 3-4, 5-7 and 8-10 components, respectively). Low intake of sugar
sweetened beverages and red meat, as well as high intake of fish, were inversely
associated with advanced polyps (OR = 0.56, 95%CI: 0.36-0.87; OR = 0.63, 95%CI:
0.42-0.95; and OR = 0.66, 95%CI: 0.44-0.99, respectively), while only low intake
of red meat was inversely associated with non-advanced adenomas (OR = 0.71,
95%CI: 0.49-0.97). CONCLUSION: A better adherence to the MD, specifically low
intake of sugar-sweetened beverages and red meat as well as high intake of fish,
is related to lower odds for advanced polyps.
PMID- 29962819
TI - Comparison between uncut Roux-en-Y and Roux-en-Y reconstruction after distal
gastrectomy for gastric cancer: A meta-analysis.
AB - AIM: To compare uncut Roux-en-Y (U-RY) gastrojejunostomy with Roux-en-Y (RY)
gastrojejunostomy after distal gastrectomy (DG) for gastric cancer. METHODS: A
literature search was conducted in Pubmed, Embase, Web of Science, Cochrane
Library, Science Direct, Chinese National Knowledge Infrastructure, Wanfang, and
China Science and Technology Journal Database to identify studies comparing U-RY
with RY after DG for gastric cancer until the end of December 2017. Pooled odds
ratio or weighted mean difference with 95% confidence interval was calculated
using either fixed- or random-effects models. Perioperative outcomes such as
operative time, intraoperative blood loss, and hospital stay; postoperative
complications such as anastomotic bleeding, stricture and ulcer, reflux
gastritis/esophagitis, delayed gastric emptying, and Roux stasis syndrome; and
postoperative nutritional status (serum hemoglobin, total protein, and albumin
levels) were the main outcomes assessed. Meta-analyses were performed using
RevMan 5.3 software. RESULTS: Two randomized controlled trials and four
nonrandomized observational clinical studies involving 403 and 488 patients,
respectively, were included. The results of the meta-analysis showed that
operative time [weighted mean difference (WMD): -12.95; 95%CI: -22.29 to -3.61; P
= 0.007] and incidence of reflux gastritis/esophagitis (OR: 0.40; 95%CI: 0.20
0.80; P = 0.009), delayed gastric emptying (OR: 0.29; 95%CI: 0.14-0.61; P =
0.001), and Roux stasis syndrome (OR: 0.14; 95%CI: 0.04-0.50; P = 0.002) were
reduced; and the level of serum albumin (WMD: 0.71; 95%CI: 0.24-1.19; P = 0.003)
was increased in patients undergoing U-RY reconstruction compared with those
undergoing RY reconstruction. No differences were found with respect to
intraoperative blood loss, hospital stay, anastomotic bleeding, anastomotic
stricture, anastomotic ulcer, the levels of serum hemoglobin, and serum total
protein. CONCLUSION: U-RY reconstruction has some clinical advantages over RY
reconstruction after DG.
PMID- 29962820
TI - Primary hepatic neuroendocrine tumor case with a preoperative course of 26 years:
A case report and literature review.
AB - Primary hepatic neuroendocrine tumor (PHNET) is an extremely rare liver tumor.
Patients often have no clinical symptoms or have only non-specific symptoms, such
as abdominal pain and abdominal mass. The clinical manifestations, disease
development, treatment methods, and treatment outcomes of PHNET vary greatly
among cases. Here we report a case of PHNET with a confirmed 26-year survival
before surgery. The patient was a 56-year-old female. A large right hepatic mass
was detected when the patient was 30 years old. The tumor could not be removed
during exploratory laparotomy, and constriction of the right hepatic artery and
biopsy were conducted. Pathological results indicated a diagnosis of benign
tumor, but a confirmed diagnosis was not reached. Twenty-six years after the
patient had been living with the tumor, she sought treatment again because of
tumor progression. After systematic evaluation of the resectability, the tumor
was resected. Based on the examination results of the gastrointestinal tract and
lungs, intraoperative examination results, pathological findings, and long-term
follow-up results, the diagnosis of PHNET was confirmed. This case represents the
longest reported survival time for a PHNET patient before removal of the tumor.
PMID- 29962821
TI - Boundary value problems for hypergenic function vectors.
AB - This article mainly studies the boundary value problems for hypergenic function
vectors in Clifford analysis. Firstly, some properties of hypergenic quasi-Cauchy
type integrals are discussed. Then, by the Schauder fixed point theorem the
existence of the solution to the nonlinear boundary value problem is proved.
Finally, using the compression mapping principle the existence and uniqueness of
the solution to the linear boundary value problem are proved.
PMID- 29962822
TI - Evaluating relationships between total dissolved solids (TDS) and total suspended
solids (TSS) in a mining-influenced watershed.
AB - Measurement of total suspended solids (TSS) and total dissolved solids (TDS)
loadings in streams is often used to assess potential impacts from mining on
surface water quality within a drainage basin. It has been suggested that TSS
could be used as an indicator to estimate TDS loading through the use of a
TDS/TSS ratio. The reliability of this approach was tested by examining empirical
linear relationships between TSS and TDS loads at three locations within a mining
influenced watershed in Colorado. Predictive accuracy of the relationships was
assessed using an independent source of data for the same locations, with
comparisons between estimated and observed TDS loads for periods within and
outside the years used to develop relationships. Evaluations were conducted over
the entire flow regime and for separate periods of low- and high-flow. Improved
representation of the data was achieved by incorporation of a regressed average
baseflow contribution, indicating the relationship between TDS and TSS loads is
not accurately represented by a simple ratio. High variability in data between
locations prevents application of a basin scale relationship to all locations
within that basin. Local-scale relationships developed under specific flow
regimes resulted in more accurate predictions, but results suggest that factors
additional to flow may need to be considered to improve predictability.
Usefulness of linear empirical relationships to predict TDS load from TSS load
will depend on the magnitude of uncertainty that is tolerable for a given
situation.
PMID- 29962823
TI - 25 Years of Complex Intervention Trials: Reflections on Lived and Scientific
Experiences.
AB - For the past 25 years, I have led multiple group-randomized trials, each focused
on a specific underserved population of youth and each one evaluated health
effects of complex interventions designed to prevent high-risk behaviors. I share
my reflections on issues of intervention and research design, as well as how
research results fostered my evolution toward addressing fundamental social
determinants of health and well-being. Reflections related to intervention design
emphasize the importance of careful consideration of theory of causes and theory
of change, theoretical comprehensiveness versus fundamental determinants of
population health, how high to reach, and health in all policies. Flowing from
these intervention design issues are reflections on implications for research
design, including the importance of matching the unit of intervention to the unit
of assignment, the emerging field of public health law research, and
consideration of design options and design elements beyond and in combination
with random assignment.
PMID- 29962824
TI - Optimal Mass Transport: Signal processing and machine-learning applications.
AB - Transport-based techniques for signal and data analysis have received increased
attention recently. Given their ability to provide accurate generative models for
signal intensities and other data distributions, they have been used in a variety
of applications including content-based retrieval, cancer detection, image super
resolution, and statistical machine learning, to name a few, and shown to produce
state of the art results in several applications. Moreover, the geometric
characteristics of transport-related metrics have inspired new kinds of
algorithms for interpreting the meaning of data distributions. Here we provide a
practical overview of the mathematical underpinnings of mass transport-related
methods, including numerical implementation, as well as a review, with
demonstrations, of several applications. Software accompanying this tutorial is
available at [43].
PMID- 29962825
TI - Differential Response to Heart Failure Medications in Children.
AB - There have been many advances in the treatment of heart failure over the past
several years. While these advancements have resulted in improved outcomes in
adults with heart failure, these same treatments do not seem to be as efficacious
in children with heart failure. Investigations of the failing pediatric heart
suggest that there are unique phenotypic, pathologic and molecular differences
that could influence how children with heart failure response to adult-based
therapies. In this review, several recent studies and the potential implications
of their findings on informing the future of the management of pediatric heart
failure are discussed.
PMID- 29962826
TI - Implementation of a Curriculum-Integrated Computer Game for Introducing
Scientific Argumentation.
AB - Argumentation has been emphasized in recent U.S. science education reform efforts
(NGSS Lead States 2013; NRC 2012), and while existing studies have investigated
approaches to introducing and supporting argumentation (e.g., McNeill & Krajcik
2008; Kang, Thompson &Windschitl 2014), few studies have investigated how game
based approaches may be used to introduce argumentation to students. In this
paper, we report findings from a design-based study of a teacher's use of a
computer game intended to introduce the Claim, Evidence, Reasoning (CER)
framework (McNeill &Krajcik 2012) for scientific argumentation. We studied the
implementation of the game over two iterations of development in a high school
biology teacher's classes. The results of this study include aspects of enactment
of the activities and student argument scores. We found the teacher used the game
in aspects of explicit instruction of argumentation during both iterations,
although the ways in which the game was used differed. Also, students' scores in
the second iteration were significantly higher than the first iteration. These
findings support the notion that students can learn argumentation through a game,
especially when used in conjunction with explicit instruction and support in
student materials. These findings also highlight the importance of analyzing
classroom implementation in studies of game-based learning.
PMID- 29962827
TI - Informed Consent in Translational Genomics: Insufficient Without Trustworthy
Governance.
PMID- 29962829
TI - Gap Flow Simulation Methods in High Pressure Variable Displacement Axial Piston
Pumps.
AB - High pressure variable displacement axial piston pumps are subject to complex
dynamic phenomena. Their analysis is difficult, additionally complicated by
leakage of the working fluid. Analytically gap flow is calculated with the
Reynolds equation which describes the pressure distribution in a thin lubricating
layer. The paper presents various approaches to analyze gap flow both in
traditional axial piston pump and novel type of hydraulic pump, designed at the
Polish Gdansk Institute of Technology. Because of large aspect ratio between the
height of the gap and the size of pump elements, the authors present the
numerical simulation approach using a local model to define a lubrication gap,
linked to a global model of a pump from which boundary conditions were imported.
User defined functions implemented in Fluent and Excel were used to calculate the
pressure and velocity fields and assess the fluid flow rate.
PMID- 29962830
TI - Application of the Numerical Techniques for Modelling Fluidization Process Within
Industrial Scale Boilers.
AB - The numerical simulation of the large scale industrial circulating fluidized bed
(CFB) boilers, working under air- and oxy-fuel combustion are presented in this
paper. Moreover, two-dimensional experimental rig used for numerical model
validation is described. For three-dimensional numerical simulations two
industrial compact CFB boilers were selected installed in Polish Power Plants.
Numerical simulations were carried out using three-dimensional model where the
dense particulate transport phenomenon was simultaneously modelled with
combustion process. The fluidization process was modelled using the hybrid Euler
Lagrange approach. Within the paper, readers can find information about used
computational technique and a number of reference to specific work. The impact of
radiative heat transfer on predicted temperature profile within the CFB boiler
was investigated in presented work. Moreover, the novel model for retrieving
radiative properties of gases under oxy-fuel combustion process was used. The
evaluated temperature and pressure profiles during numerical simulations were
compared against measured data collected during boiler air-fuel operation.
Collected data was also used for validating numerical model of the oxy-fuel
combustion model. Stability of the model and its sensitivity on changes of
composition of the oxidizer were studied. This simulations were evaluated to
check the response of the numerical model on changing the combustion conditions
from air- to oxy-fuel combustion process. The comparison of the pressure and
temperature profiles for all considered cases gave comparable trends in contrary
to measured data.
PMID- 29962828
TI - Insomnia among non-depressed multiple sclerosis patients: a cross-sectional
study.
AB - Background: Insomnia is a common problem that affects approximately 50% of
patients with multiple sclerosis (MS), who suffer from sleep disturbances. In
general, persons with insomnia are at a higher risk of developing depression.
This study was conducted to assess insomnia among non-depressed MS patients in
Saudi Arabia. Methods: Based on the Patient Health Questionnaire-9 (PHQ-9), those
who scored 4 or less for depression out of 598 MS patients were selected (n =
112). A cross-sectional study was conducted to interview 112 non-depressed MS
patients in order to assess insomnia among them. A data collection sheet has been
designed by the researchers. It comprised socio-demographic variables (e.g.,
gender, age, area of residence, and marital status) and clinical variables
(disease duration, age at disease onset, previous diagnosis of depression, and
used antidepressant drugs). Insomnia was assessed by the Insomnia Severity Index
(ISI), while severity of illness was assessed using the Patient Determined
Disease Steps (PDDS). Results: A total of 72 patients (64.3%) were females, and
62 (55.4%) were married. Their mean age was 32.6 years (SD = 8.9), ranging from
15 to 56 years. As for educational level, 64 (57.1%) had a Bachelor degree. The
mean age at disease onset was 26 years (SD = 8.9). The mean duration of illness
was 1.9 years. Symptoms of insomnia were present among 14 patients (12.5%). No
statistical significance was found between the mean PDSS of insomnia and non
insomnia patients. Significant differences were present between insomnia and non
insomnia patients as regards their education level (P = 0.005) and use of
antidepressant drugs (P = 0.008). Conclusions: Prevalence of insomnia among non
depressed MS patients is low. Insomnia is associated with educational and use of
antidepressants. Further research is needed to assess severity of different types
of insomnia among depressed and non-depressed MS patients.
PMID- 29962831
TI - FEMPAR: An Object-Oriented Parallel Finite Element Framework.
AB - FEMPAR is an open source object oriented Fortran200X scientific software library
for the high-performance scalable simulation of complex multiphysics problems
governed by partial differential equations at large scales, by exploiting state
of-the-art supercomputing resources. It is a highly modularized, flexible, and
extensible library, that provides a set of modules that can be combined to carry
out the different steps of the simulation pipeline. FEMPAR includes a rich set of
algorithms for the discretization step, namely (arbitrary-order) grad, div, and
curl-conforming finite element methods, discontinuous Galerkin methods, B
splines, and unfitted finite element techniques on cut cells, combined with h
adaptivity. The linear solver module relies on state-of-the-art bulk-asynchronous
implementations of multilevel domain decomposition solvers for the different
discretization alternatives and block-preconditioning techniques for multiphysics
problems. FEMPAR is a framework that provides users with out-of-the-box state-of
the-art discretization techniques and highly scalable solvers for the simulation
of complex applications, hiding the dramatic complexity of the underlying
algorithms. But it is also a framework for researchers that want to experience
with new algorithms and solvers, by providing a highly extensible framework. In
this work, the first one in a series of articles about FEMPAR, we provide a
detailed introduction to the software abstractions used in the discretization
module and the related geometrical module. We also provide some ingredients about
the assembly of linear systems arising from finite element discretizations, but
the software design of complex scalable multilevel solvers is postponed to a
subsequent work.
PMID- 29962832
TI - Plant Species Identification Using Computer Vision Techniques: A Systematic
Literature Review.
AB - Species knowledge is essential for protecting biodiversity. The identification of
plants by conventional keys is complex, time consuming, and due to the use of
specific botanical terms frustrating for non-experts. This creates a hard to
overcome hurdle for novices interested in acquiring species knowledge. Today,
there is an increasing interest in automating the process of species
identification. The availability and ubiquity of relevant technologies, such as,
digital cameras and mobile devices, the remote access to databases, new
techniques in image processing and pattern recognition let the idea of automated
species identification become reality. This paper is the first systematic
literature review with the aim of a thorough analysis and comparison of primary
studies on computer vision approaches for plant species identification. We
identified 120 peer-reviewed studies, selected through a multi-stage process,
published in the last 10 years (2005-2015). After a careful analysis of these
studies, we describe the applied methods categorized according to the studied
plant organ, and the studied features, i.e., shape, texture, color, margin, and
vein structure. Furthermore, we compare methods based on classification accuracy
achieved on publicly available datasets. Our results are relevant to researches
in ecology as well as computer vision for their ongoing research. The systematic
and concise overview will also be helpful for beginners in those research fields,
as they can use the comparable analyses of applied methods as a guide in this
complex activity.
PMID- 29962834
TI - Oncology education for internal medicine residents: a call for action!
PMID- 29962833
TI - Multiscale Molecular Simulations of Polymer-Matrix Nanocomposites: or What
Molecular Simulations Have Taught us About the Fascinating Nanoworld.
AB - Following the substantial progress in molecular simulations of polymer-matrix
nanocomposites, now is the time to reconsider this topic from a critical point of
view. A comprehensive survey is reported herein providing an overview of
classical molecular simulations, reviewing their major achievements in modeling
polymer matrix nanocomposites, and identifying several open challenges. Molecular
simulations at multiple length and time scales, working hand-in-hand with
sensitive experiments, have enhanced our understanding of how nanofillers alter
the structure, dynamics, thermodynamics, rheology and mechanical properties of
the surrounding polymer matrices.
PMID- 29962835
TI - Comprehensive metastatic lung cancer care must include palliative care.
PMID- 29962836
TI - The survivorship care plan: a valuable tool for primary care providers?
PMID- 29962837
TI - What do primary care providers think about implementing breast cancer
survivorship care?
AB - Purpose: As cancer centres move forward with earlier discharge of stable
survivors of early-stage breast cancer (bca) to primary care follow-up, it is
important to address known knowledge and practice gaps among primary care
providers (pcps). In the present qualitative descriptive study, we examined the
practice context that influences implementation of existing clinical practice
guidelines for providing such care. The purpose was to determine the challenges,
strengths, and opportunities related to implementing comprehensive evidence-based
bca survivorship care guidelines by pcps in southeastern Ontario. Methods: Semi
structured interviews were conducted with 19 pcps: 10 physicians and 9 nurse
practitioners. Results: Thematic analysis revealed 6 themes within the broad
categories of knowledge, attitudes, and resources. Participants highlighted 3
major challenges related to providing bca survivorship care: inconsistent
educational preparation, provider anxieties, and primary care burden. They also
described 3 major strengths or opportunities to facilitate implementation of
survivorship care guidelines: tools and technology, empowering survivors, and
optimizing nursing roles. Conclusions: We identified several important challenges
to implementation of comprehensive evidence-based survivorship care for bca
survivors, as well as several strengths and opportunities that could be built
upon to address those challenges. Findings from our research could inform
targeted knowledge translation interventions to provide support and education for
pcps and bca survivors.
PMID- 29962838
TI - Medical oncology workload in Canada: infrastructure, supports, and delivery of
clinical care.
AB - Background: In 2000, a Canadian task force recommended that medical oncologists
(mos) meet a target of 160-175 new patient consultations per year. Here, we
report the Canadian results of a global survey of mo workload compared with mo
workload in other high-income countries (hics). Methods: Using a snowball method,
an online survey was distributed by national oncology societies to chemotherapy
prescribing physicians in 22 hics (World Bank criteria). The survey was
distributed within Canada to all members of the Canadian Association of Medical
Oncologists. Workload was measured as the annual number of new cancer patient
consults per oncologist. Results: The survey was completed by 782 oncologists
from hics, including 58 from Canada. Median annual consults per mo were 175 in
Canada compared with 125 in other hics. The proportions of mos having 100 or
fewer consults or more than 300 consults per year were 3% (2/58) and 5% (3/58) in
Canada compared with 31% (222/724) and 16% (116/724) in other hics (p < 0.001 and
p = 0.023 respectively). The median number of patients seen in a full-day clinic
was 15 in Canada and 25 in other hics (p = 0.220). Canadian mos reported spending
a median of 55 minutes per new consultation; new consultations of 35 minutes were
reported in other hics (p < 0.001). Median hours worked per week was 55 in Canada
and 45 in other hics (p = 0.200). Conclusions: Although the median annual
clinical volume for Canadian mos aligns with recommended targets, half the
respondents exceeded that level of activity. Health policymakers and educators
have to consider mo workforce supply and alternative models of care in
preparation for the anticipated surge in cancer incidence in the coming decade.
PMID- 29962839
TI - Oncology education for Canadian internal medicine residents: the value of
participating in a medical oncology elective rotation.
AB - Background: Despite the high incidence and burden of cancer in Canadians, medical
oncology (mo) rotations are not mandatory in most Canadian internal medicine (im)
residency training programs. Methods: All im residents scheduled for a mo
rotation at 4 Canadian teaching cancer centres between 1 January 2013 and 31
December 2015 were invited to complete an online survey before and after their
rotation. The survey was designed to evaluate perceptions of oncology, comfort in
managing cancer patients, and basic oncology knowledge. Results: The survey was
completed by 68 im residents pre-rotation and by 48 (71%) post-rotation. Cancer
related learning was acquired mostly from mo physicians in clinic (35%). Self
directed learning, didactic teaching, and resident or fellow teaching accounted
for 31%, 26%, and 10% respectively of learning acquisition. Comfort level in
dealing with cancer patients and patients at end of life improved to 4.0/5 from
3.2/5 (p < 0.001) and to 4.0/5 from 3.6/5 (p = 0.003) respectively. Mean
knowledge assessment score improved to 83% post-rotation from 76% pre-rotation (p
= 0.003), with the greatest increase observed in general knowledge of common
malignancies. The 3 topics ranked as most important to learn during a mo rotation
were oncologic emergencies, common complications of treatment, and approach to
diagnosis of cancer. Conclusions: A rotation in mo improves the perceptions of im
residents about oncology and their comfort level in dealing with cancer patients
and patients at end of life. Overall cancer knowledge is also improved. Given
those benefits, im residency programs should encourage most of their residents to
complete a mo rotation.
PMID- 29962840
TI - Rates of cannabis use in patients with cancer.
AB - Background: A comprehensive assessment of cannabis use by patients with cancer
has not previously been reported. In this study, we aimed to characterize patient
perspectives about cannabis and its use. Methods: An anonymous survey about
cannabis use was offered to patients 18 years of age and older attending 2
comprehensive and 2 community cancer centres, comprising an entire provincial
health care jurisdiction in Canada (ethics id: hreba-17011). Results: Of 3138
surveys distributed, 2040 surveys were returned (65%), with 1987 being
sufficiently complete for analysis (response rate: 63%). Of the respondents, 812
(41%) were less than 60 years of age; 45% identified as male, and 55% as female;
and 44% had completed college or higher education.Of respondents overall, 43%
reported any lifetime cannabis use. That finding was independent of age, sex,
education level, and cancer histology. Cannabis was acquired through friends
(80%), regulated medical dispensaries (10%), and other means (6%). Of patients
with any use, 81% had used dried leaves.Of the 356 patients who reported cannabis
use within the 6 months preceding the survey (18% of respondents with
sufficiently complete surveys), 36% were new users. Their reasons for use
included cancer-related pain (46%), nausea (34%), other cancer symptoms (31%),
and non-cancer-related reasons (56%). Conclusions: The survey demonstrated that
prior cannabis use was widespread among patients with cancer (43%). One in eight
respondents identified at least 1 cancer-related symptom for which they were
using cannabis.
PMID- 29962841
TI - How can we better help cancer patients quit smoking? The London Regional Cancer
Program experience with smoking cessation.
AB - Background: Because continued cigarette smoking after a cancer diagnosis is
associated with detrimental outcomes, supporting cancer patients with smoking
cessation is imperative. We evaluated the effect of the Smoking Cessation Program
at the London Regional Cancer Program (lrcp) over a 2-year period. Methods: The
Smoking Cessation Program at the lrcp began in March 2014. New patients are
screened for tobacco use. Tobacco users are counselled about the benefits of
cessation and are offered referral to the program. If a patient accepts, a
smoking cessation champion offers additional counselling. Follow-up is provided
by interactive voice response (ivr) telephone system. Accrual data were collected
monthly from January 2015 to December 2016 and were evaluated. Results: During
2015-2016, 10,341 patients were screened for tobacco use, and 18% identified
themselves as current or recent tobacco users. In 2015, 84% of tobacco users were
offered referral, but only 13% accepted, and 3% enrolled in ivr follow-up. At the
lrcp in 2016, 77% of tobacco users were offered referral to the program, but only
9% of smokers accepted, and only 2% enrolled in ivr follow-up. Conclusions: The
Smoking Cessation Program at the lrcp has had modest success, because multiple
factors influence a patient's success with cessation. Limitations of the program
include challenges in referral and counselling, limited access to nicotine
replacement therapy (nrt), and minimal follow-up. To mitigate some of those
challenges, a pilot project was launched in January 2017 in which patients
receive free nrt and referral to the local health unit.
PMID- 29962842
TI - The north-south and east-west gradient in colorectal cancer risk: a look at the
distribution of modifiable risk factors and incidence across Canada.
AB - Colorectal cancer (crc) is the 2nd most common cancer in Canada and the 2nd
leading cause of cancer death. That heavy burden can be mitigated given the
preventability of crc through lifestyle changes and screening. Here, we describe
the extent of the variation in crc incidence rates across Canada and the
disparities, by jurisdiction, in the prevalence of modifiable risk factors known
to contribute to the crc burden. Findings suggest that there is a north-south and
east-west gradient in crc modifiable risk factors, including excess weight,
physical inactivity, excessive alcohol consumption, and low fruit and vegetable
consumption, with the highest prevalence of risk factors typically found in the
territories and Atlantic provinces. In general, that pattern reflects the crc
incidence rates seen across Canada. Given the substantial interjurisdictional
variation, more work is needed to increase prevention efforts, including
promoting a healthier diet and lifestyle, especially in jurisdictions facing
disproportionately higher burdens of crc. Based on current knowledge, the most
effective approaches to reduce the burden of crc include adopting public policies
that create healthier environments in which people live, work, learn, and play;
making healthy choices easier; and continuing to emphasize screening and early
detection. Strategic approaches to modifiable risk factors and mechanisms for
early cancer detection have the potential to translate into positive effects for
population health and fewer Canadians developing and dying from cancer.
PMID- 29962843
TI - Ode to my oncologist.
PMID- 29962844
TI - Comparing enrolees with non-enrolees of cancer-patient navigation at end of life.
AB - Background: Cancer-patient navigators who are oncology nurses support and connect
patients to resources throughout the cancer care trajectory, including end of
life. Although qualitative and cohort studies of navigated patients have been
reported, no population-based studies were found. The present population-based
study compared demographic, disease, and outcome characteristics for decedents
who had been diagnosed with cancer by whether they did or did not see a
navigator. Methods: This retrospective study used patient-based administrative
data in Nova Scotia (cancer registry, death certificates, navigation visits) to
generate descriptive statistics. The study population included all adults
diagnosed with cancer who died during 2011-2014 of a cancer or non-cancer cause
of death. Results: Of the 7694 study decedents, 74.9% had died of cancer. Of
those individuals, 40% had seen a navigator at some point in their disease
trajectory. The comparable percentage for those who did not die of cancer was
11.9%. Decedents at the oldest ages had the lowest navigation rates. Navigation
rates, time from diagnosis to death, and time from last navigation visit to death
varied by disease site. Conclusions: This population-based study of cancer
patient navigation enrolees compared with non-enrolees is the first of its kind.
Most findings were consistent with expectations. However, we do not know whether
the rates of navigation are consistent with the navigation needs of the
population diagnosed with cancer. Because more people are living longer with
cancer and because the population is aging, ongoing surveillance of who requires
and who is using navigation services is warranted.
PMID- 29962845
TI - A bioimpedance analysis of head-and-neck cancer patients undergoing radiotherapy.
AB - Malnutrition is a frequent manifestation in patients with head-and-neck cancer
undergoing radiation therapy and a major contributor to morbidity and mortality.
Thus, body composition is an important component of an overall evaluation of
nutrition in cancer patients. Malnutrition is characterized by weight loss, loss
of muscle mass, changes in cell membrane integrity, and alterations in fluid
balance. Bioelectrical impedance analysis is a method to analyze body composition
and includes parameters such as intracellular water content, extracellular water
content, and cell membrane integrity in the form of a phase angle (Phi).
Bioelectrical impedance analysis has consistently been shown to have prognostic
value with respect to mortality and morbidity in patients undergoing
chemotherapy. The goal of the present study was to evaluate the relationship
between Phi, time, intracellular water content, and weight for head-and-neck
cancer patients undergoing radiotherapy. The results demonstrate that Phi
decreases with time and increases with intracellular water content and weight.
PMID- 29962846
TI - Glove and instrument changing to prevent tumour seeding in cancer surgery: a
survey of surgeons' beliefs and practices.
AB - Background: Some surgeons change gloves and instruments after the extirpative
phase of cancer surgery with the intent of reducing the risk of local and wound
recurrence. Although this practice is conceptually appealing, the evidence that
gloves or instruments act as vectors of cancer-cell seeding in the clinical
setting is weak. To determine the potential effect of further investigation of
this question, we surveyed the practices and beliefs of a broad spectrum of
surgeons who operate on cancer patients. Methods: Using a modified Dillman
approach, a survey was mailed to all 945 general surgeons listed in the College
of Physicians and Surgeons of Ontario public registry. The survey consisted of
multiple-choice and free-text response questions. Responses were tabulated and
grouped into themes, including specific intraoperative events and surgeon
training. Predictive variables were analyzed by chi-square test. Results: Of 459
surveys returned (adjusted response rate: 46%), 351 met the inclusion criteria
for retention. Of those respondents, 52% reported that they change gloves during
cancer resections with the intent of decreasing the risk of tumour seeding, and
40%, that they change instruments for that purpose. The proportion of respondents
indicating that they take measures to protect the wound was 73% for laparoscopic
cancer resections and 31% for open resections. Training and years in practice
predicted some of the foregoing behaviours. The most commonly cited basis for
adopting specific strategies to prevent tumour seeding was "gut feeling,"
followed by clinical training. Most respondents believe that it is possible or
probable that surgical gloves or instruments harbour malignant cells, but that a
cancer recurrence proceeding from that situation is unlikely. Conclusions: There
is no consensus on how gloves and instruments should be handled in cancer
operations. Further investigation is warranted.
PMID- 29962847
TI - Harmonization of PD-L1 testing in oncology: a Canadian pathology perspective.
AB - Checkpoint inhibitors targeting the programmed cell death 1 protein (PD-1) and
programmed cell death ligand 1 (PD-L1) are demonstrating promising efficacy and
appear to be well tolerated in a number of tumour types. In non-small-cell lung
cancer, head-and-neck squamous cell carcinoma, and urothelial carcinoma, outcomes
appear particularly favourable in patients with high PD-L1 expression. However,
assays for PD-L1 have been developed for individual agents, and they use
different antibody clones, immunohistochemistry staining protocols, scoring
algorithms, and cut-offs. Given that laboratories are unlikely to use multiple
testing platforms, use of one PD-L1 assay in conjunction with a specific therapy
will become impractical and could compromise treatment options. Methods to
harmonize testing methods are therefore crucial to ensuring appropriate treatment
selection. This paper focuses on lung, bladder, and head-and-neck cancer. It
reviews and compares available PD-L1 testing methodologies, summarizes the
literature about comparability studies to date, discusses future directions in
personalized diagnostics, and provides a pathologist's perspective on PD-L1
testing in the Canadian laboratory setting.
PMID- 29962848
TI - Overcoming resistance in a BRAF V600E-mutant adenocarcinoma of the lung.
AB - We report on a patient with an adenocarcinoma of the lung harbouring a BRAF V600E
mutation who benefited from combination therapy with dabrafenib-trametinib after
developing resistance to vemurafenib. To our knowledge, our report shows, for the
first time, that combination therapy with dabrafenib-trametinib can overcome
vemurafenib resistance in a BRAF V600E-mutated adenocarcinoma of the lung.
PMID- 29962849
TI - Anastomosing hemangioma of the kidney: radiologic and pathologic distinctions of
a kidney cancer mimic.
AB - Anastomosing hemangioma (ah) is a rare subtype of primary vascular tumour that
can, clinically and radiologically, present similarly to malignant renal tumours
such as renal cell carcinoma (rcc) and angiosarcoma. Rarely seen in the
genitourinary system, the ah we report here occurred in a 40-year-old male
patient diagnosed initially with rcc based on imaging and successfully treated by
laparoscopic left radical nephrectomy, with adrenal sparing and perihilar lymph
node dissection. The pathologic diagnosis of ah can be challenging on small
biopsy specimens; we therefore opine that it is appropriate to excise these
lesions to facilitate diagnosis and definitively exclude common renal cancers.
However, in this review, we describe some radiologic and pathologic distinctions
between ah and malignant tumours.
PMID- 29962850
TI - Role of peripheral vestibular receptors in the control of blood pressure
following hypotension.
AB - Hypotension is one of the potential causes of dizziness. In this review, we
summarize the studies published in recent years about the electrophysiological
and pharmacological mechanisms of hypotension-induced dizziness and the role of
the vestibular system in the control of blood pressure in response to
hypotension. It is postulated that ischemic excitation of the peripheral
vestibular hair cells as a result of a reduction in blood flow to the inner ear
following hypotension leads to excitation of the central vestibular nuclei, which
in turn may produce dizziness after hypotension. In addition, excitation of the
vestibular nuclei following hypotension elicits the vestibulosympathetic reflex,
and the reflex then regulates blood pressure by a dual-control (neurogenic and
humoral control) mechanism. In fact, recent studies have shown that peripheral
vestibular receptors play a role in the control of blood pressure through neural
reflex pathways. This review illustrates the dual-control mechanism of peripheral
vestibular receptors in the regulation of blood pressure following hypotension.
PMID- 29962851
TI - Isoliquiritigenin attenuates spinal tuberculosis through inhibiting immune
response in a New Zealand white rabbit model.
AB - Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis
(Mtb) infections in spinal curds. Isoliquiritigenin 4,2',4'-trihydroxychalcone,
ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza
uralensis), a Chinese traditional medicine. In this study, we evaluated the
potential of ISL in treating ST in New Zealand white rabbit models. In the model,
rabbits (n=40) were infected with Mtb strain H37Rv or not in their 6th lumbar
vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg
and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent
vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin
staining. The relative expression of Monocyte chemoattractant protein-1 (MCP
1/CCL2), transcription factor kappaB (NF-kappaB) p65 in lymphocytes were verified
through reverse transcription quantitative real-time PCR (RT-qPCR), western
blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of
interleukin (IL)-2, IL-4, IL-10 and interferon gamma (IFN-gamma) were evaluated
through ELISA. The effects of ISL on the phosphorylation of IkappaBalpha,
IKKalpha/beta and p65 in NF-kappaB signaling pathways were assessed through
western blotting. In the results, ISL has been shown to effectively attenuate the
granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65
and IL-4 and IL-10 were retrieved. NF-kappaB signaling was inhibited, in which
the phosphorylation of p65, IkappaBalpha and IKKalpha/beta were suppressed
whereas the level of IkappaBalpha were elevated. In conclusion, ISL might be an
effective drug that inhibited the formation of granulomas through downregulating
MCP-1, NF-kappaB, IL-4 and IL-10 in treating ST.
PMID- 29962852
TI - Adenine attenuates lipopolysaccharide-induced inflammatory reactions.
AB - A nucleobase adenine is a fundamental component of nucleic acids and adenine
nucleotides. Various biological roles of adenine have been discovered. It is not
produced from degradation of adenine nucleotides in mammals but produced mainly
during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine
have been supported in IgE-mediated allergic reactions, immunological functions
of lymphocytes and dextran sodium sulfate-induced colitis. However adenine
effects on Toll-like receptor 4 (TLR4)-mediated inflammation by
lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not
examined. Here we investigated anti-inflammatory roles of adenine in LPS
stimulated immune cells, including a macrophage cell line RAW264.7 and bone
marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells
stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines
TNF-alpha and IL-6 and inflammatory lipid mediators, prostaglandin E2 and
leukotriene B4. Adenine impeded signaling pathways eliciting production of these
inflammatory mediators. It suppressed IkappaB phosphorylation, nuclear
translocation of nuclear factor kappaB (NF-kappaB), phosphorylation of Akt and
mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised
cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme
activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production
of TNF-alpha, IL-6 and IL-13 and also hindered phosphorylation of NF-kappaB and
Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of TNF
alpha and IL-6 by peritoneal cells in mice. These results show that adenine
attenuates the LPS-induced inflammatory reactions.
PMID- 29962854
TI - Lipidomic analysis of plasma lipids composition changes in septic mice.
AB - A lipidomic study on extensive plasma lipids in bacterial peritonitis (cecal
ligation and puncture, CLP)-induced sepsis in mice was done at 24 h post-CLP. The
effects of administration of lysophosphatidylcholine (LPC) and lysophosphatidic
acid (LPA), compounds known to have beneficial effects in CLP, on the sepsis
induced plasma lipid changes were also examined. Among the 147 plasma lipid
species from 13 lipid subgroups (fatty acid [FA], LPA, LPC,
lysophosphatidylethanolamine [LPE], phosphatidic acid [PA], phosphatidylcholine
[PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], monoacylglyceride
[MG], diacylglyceride [DG], triacylglyceride [TG], sphingomyelin [SM], and
ceramide [Cer]) analyzed in this study, 40 and 70 species were increased, and
decreased, respectively, in the CLP mice. Treatments with LPC and LPA affected 14
species from 7 subgroups, and 25 species from 9 subgroups, respectively. These
results could contribute to finding the much needed reliable biomarkers of
sepsis.
PMID- 29962853
TI - Anti-inflammatory and utero-relaxant effect of alpha-bisabolol on the pregnant
human uterus.
AB - The aim of this study was to evaluate the in vitro anti-inflammatory and utero
relaxant effect of alpha-bisabolol on the pregnant human myometrium. Samples from
the pregnant human myometrium were used in functional tests to evaluate the
inhibitory effect of alpha-bisabolol (560, 860, 1,200 and 1,860 uM) on
spontaneous myometrial contractions. The intracellular cyclic adenosine
monophosphate (cAMP) levels generated in response to alpha-bisabolol in human
myometrial homogenates were measured by ELISA. The anti-inflammatory effect of
alpha-bisabolol was determined through the measurement of two pro-inflammatory
cytokines, tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta, and
the anti-inflammatory cytokine IL-10, in pregnant human myometrial explants
stimulated with lipopolysaccharide (LPS). Forskolin was used as a positive
control to evaluate the cAMP and cytokine levels. alpha-Bisabolol was found to
induce a significant inhibition of spontaneous myometrial contractions at the
highest concentration level (p<0.05). alpha-Bisabolol caused a concentration
dependent decrease in myometrial cAMP levels (p<0.05) and a concentration
dependent decrease in LPS-induced TNFalpha and IL-1beta production, while IL-10
production did not increase significantly (p>0.05). The anti-inflammatory and
utero-relaxant effects induced by alpha-bisabolol were not associated with an
increase in cAMP levels in pregnant human myometrial samples. These properties
place alpha-bisabolol as a potentially safe and effective adjuvant agent in cases
of preterm birth, an area of pharmacological treatment that requires urgent
improvement.
PMID- 29962855
TI - Supplementing punicalagin reduces oxidative stress markers and restores
angiogenic balance in a rat model of pregnancy-induced hypertension.
AB - Pre-eclampsia (PE) is a pregnancy disorder that is characterised by severe
hypertension and increased risks of foetal and maternal mortality. The aetiology
of PE not completely understood; however, maternal nutrition and oxidative stress
play important roles in the development of hypertension. The treatment options
for PE are currently limited to anti-hypertensive drugs. Punicalagin, a
polyphenol present in pomegranate juice, has a range of bioactive properties. The
effects of supplementation with punicalagin on angiogenesis and oxidative stress
in pregnant rats with induced hypertension were investigated. The pregnant rats
were randomly divided into five experimental groups (n=12 per group).
Hypertension was induced using an oral dose of NG-nitro-L-arginine methyl ester
(L-NAME, 50 mg/kg/day) on days 14-19 of pregnancy. Punicalagin (25, 50 or 100
mg/kg) was given orally on days 14-21 of pregnancy. Punicalagin treatment at the
tested doses significantly reduced diastolic, systolic, and mean arterial blood
pressure in L-NAME treated rats from day 14. Punicalagin also restored angiogenic
balance by increasing the expression of vascular endothelial growth factor and
downregulating vascular endothelial growth factor receptor-1/fms-like tyrosine
kinase-1. Punicalagin, significantly increased the placental nitric oxide levels
as compared to PE group. The increased levels of oxidative stress in rats with PE
were markedly decreased by treatment with punicalagin. Punicalagin at the tested
doses markedly (p<0.05) enhanced the placental antioxidant capacity in L-NAME
treated rats. The raised catalase activity observed following L-NAME induction
was significantly (p<0.05) and restored to normal activity levels in punicalagin
treatment. Further, 100 mg dose of punicalagin exhibited higher protective
effects as compared to lower doses of 25 and 50 mg. This study shows that
supplementation with punicalagin decreased blood pressure and oxidative stress
and restored angiogenic balance in pregnant rats with induced PE.
PMID- 29962856
TI - The effect of u-opioid receptor activation on GABAergic neurons in the spinal
dorsal horn.
AB - The superficial dorsal horn of the spinal cord plays an important role in pain
transmission and opioid activity. Several studies have demonstrated that opioids
modulate pain transmission, and the activation of u-opioid receptors (MORs) by
opioids contributes to analgesic effects in the spinal cord. However, the effect
of the activation of MORs on GABAergic interneurons and the contribution to the
analgesic effect are much less clear. In this study, using transgenic mice, which
allow the identification of GABAergic interneurons, we investigated how the
activation of MORs affects the excitability of GABAergic interneurons and
synaptic transmission between primary nociceptive afferent and GABAergic
interneurons. We found that a selective u-opioid agonist, [D-Ala2, NMe-Phe4, Gly
ol]-enkephanlin (DAMGO), induced an outward current mediated by K+ channels in
GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked
excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive
monosynaptic inputs from primary nociceptive C fibers. Taken together, we found
that DAMGO reduced the excitability of GABAergic interneurons and synaptic
transmission between primary nociceptive C fibers and GABAergic interneurons.
These results suggest one possibility that suppression of GABAergic interneurons
by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which
increase the inhibition of the secondary GABAergic interneurons to excitatory
neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of
the entire spinal network will control the pain transmission.
PMID- 29962857
TI - Concurrent treatment with ursolic acid and low-intensity treadmill exercise
improves muscle atrophy and related outcomes in rats.
AB - The objective of this study was to analyze the concurrent treatment effects of
ursolic acid (UA) and low-intensity treadmill exercise and to confirm the
effectiveness of UA as an exercise mimetic to safely improve muscle atrophy
related diseases using Sprague-Dawley (SD) rats with skeletal muscle atrophy.
Significant muscle atrophy was induced in male SD rats through hind limb
immobilization using casting for 10 days. The muscle atrophy-induced SD rats were
group into four: SED, sedentary; UA, daily intraperitoneal UA injection, 5 mg/kg;
EX, low-intensity (10-12 m/min, 0 degrees grade) treadmill exercise; and UEX,
daily intraperitoneal UA injection, 5 mg/kg, and low-intensity (10-12 m/min, 0
degrees grade) treadmill exercise. After 8 weeks of treatment, endurance
capacity was analyzed using a treadmill, and tissues were extracted for analysis
of visceral fat mass, body weight, muscle mass, expression of muscle atrophy- and
hypertrophy-related genes, and endurance capacity. Although the effects of body
weight gain control, muscle mass increase, and endurance capacity improvement
were inadequate in the UA group, significant results were confirmed in the UEX
group. The UEX group had significantly reduced body weight and visceral fat,
significantly improved mass of tibialis anterior and gastrocnemius muscles, and
significantly decreased atrophy-related gene expression of MuRF1 and atrogin-1,
but did not have significant change in hypertrophy-related gene expression of Akt
and mTOR. The endurance capacity was significantly improved in the EX and UEX
groups. These data suggest that concurrent treatment with low-intensity exercise
and UA is effective for atrophy-related physical dysfunctions.
PMID- 29962858
TI - alpha-Isocubebene modulates vascular tone by inhibiting myosin light chain
phosphorylation in murine thoracic aorta.
AB - alpha-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in
Schisandra chinensis (SC), a well-known medicinal herb that ameliorates
cardiovascular symptoms, but the mechanism responsible for this activity has not
been determined. To determine the role played by ICB on the regulation of
vascular tone, we investigated the inhibitory effects of ICB on vascular
contractile responses by adrenergic alpha-receptor agonists. In addition, we
investigated the role on myosin light chain (MLC) phosphorylation and cytosolic
calcium concentration in vascular smooth muscle cells (VSMC). In aortic rings
isolated from C57BL/6J mice, ICB significantly attenuated the contraction induced
by phenylephrine (PE) and norepinephrine (NE), whereas ICB had no effects on KCl
(60 mM)-induced contraction. In vasculatures precontracted with PE, ICB caused
marked relaxation of aortic rings with or without endothelium, suggesting a
direct effect on VSMC. In cultured rat VSMC, PE or NE increased MLC
phosphorylation and increased cytosolic calcium levels. Both of these effects
were significantly suppressed by ICB. In conclusion, our results showed that ICB
regulated vascular tone by inhibiting MLC phosphorylation and calcium flux into
VSMC, and suggest that ICB has anti-hypertensive properties and therapeutic
potential for cardiovascular disorders related to vascular hypertension.
PMID- 29962859
TI - Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin
type II receptor.
AB - Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme
2, has been reported to have protective effects on cardiac and vascular
remodeling. However, there is no report about the effect of Ang-(1-9) on
pulmonary hypertension. The aim of the present study is to investigate whether
Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced
pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) (576
ug/kg/day) or saline via osmotic mini-pumps for 3 weeks. Three days after
implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously
injected. MCT caused increases in right ventricular weight and systolic pressure,
which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated
endothelial damage and medial hypertrophy of pulmonary arterioles as well as
pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against
pulmonary hypertension were inhibited by Ang type 2 receptor (AT2R) blocker, but
not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory
cytokines, such as TNF-alpha, MCP-1, IL-1beta, and IL-6, in plasma were lower in
Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in
expressions of apoptosis-related proteins such as Bax, Bcl-2, Caspase-3 and -9 in
the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9).
These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension
by decreasing apoptosis and inflammatory reaction via AT2R.
PMID- 29962860
TI - Effect of BIS depletion on HSF1-dependent transcriptional activation in A549 non
small cell lung cancer cells.
AB - The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress
or anti-apoptotic protein, has been shown to be regulated at the transcriptional
level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was
also shown to bind to BIS, but the significance of these protein-protein
interactions on HSF1 activity has not been fully defined. In the present study,
we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non
small cell lung cancer did not affect the induction of heat shock protein (HSP)
70 and HSP27 mRNAs under various stress conditions such as heat shock,
proteotoxic stress, and oxidative stress. The lack of a functional association of
BIS with HSF1 activity was also demonstrated by transient downregulation of BIS
by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were
significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild
type (WT) A549 cells at the constitutive and inducible levels. The promoter
activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not
influenced by depletion of BIS. In addition, the expression levels of the mutant
BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not
different from those of the WT BIS construct, indicating that mRNA stability was
not the mechanism for autoregulation of BIS. Our results suggested that BIS was
not required for HSF1 activity, but was required for its own expression, which
involved an HSF1-independent pathway.
PMID- 29962861
TI - Recent Advances in the Image-Guided Tumor Ablation of Liver Malignancies:
Radiofrequency Ablation with Multiple Electrodes, Real-Time Multimodality Fusion
Imaging, and New Energy Sources.
AB - Radiofrequency ablation (RFA) has emerged as an effective loco-regional treatment
modality for malignant hepatic tumors. Indeed, studies have demonstrated that RFA
of early stage hepatocellular carcinomas can provide comparable overall survival
to surgical resection. However, the incidence of local tumor progression (LTP)
after RFA is significantly higher than that of surgical resection. Thus, to
overcome this limitation, multiple electrode radiofrequency (RF) systems that use
a multi-channel RF generator have been developed, and they demonstrate better
efficiency in creating larger ablation zones than that using the conventional RFA
with a single electrode. Furthermore, RFA with multiple electrodes can allow the
"no-touch" ablation technique which may also help to reduce LTP. Another
technique that would be helpful in this regard is multi-modality-ultrasound
fusion imaging, which helps to not only more accurately determine the target
lesion by enabling the RFA of small, poorly visible or invisible tumors, but also
improve the monitoring of procedures and determine the appropriateness of the
ablation margin. In addition, new energy sources, including microwave and
cryoablation, have been introduced in imaging-guided tumor ablation. In this
review, these recently introduced ablation techniques and the results of the most
current animal and clinical studies are discussed.
PMID- 29962862
TI - Comparison of Chronologic Change in the Size and Contrast-Enhancement of Ablation
Zones on CT Images after Irreversible Electroporation and Radiofrequency
Ablation.
AB - Objective: To compare short-, mid-, and long-term follow-up ablation zone volume
alterations as well as imaging features on contrast-enhanced computed tomography
(CT) after irreversible electroporation (IRE) of primary and secondary liver
tumors with findings subsequent to radiofrequency ablation (RFA). Materials and
Methods: Volume assessment of 39 ablation zones (19 RFA, 20 IRE) after
intervention was performed at four time intervals (day 0 [t1; n = 39], day 1-7
[t2; n = 25], day 8-55 [t3; n = 28], after day 55 [t4; n = 23]) on dual-phase CT.
Analysis of peripheral rim enhancement was conducted. Lesion's volume decrease
relative to the volume at t1 was calculated and statistically analyzed with
respect to patient's sex, age, ablation modality (IRE/RFA), and history of
platinum-based chemotherapy (PCT). Results: No influence of patient's sex or age
on ablation volume was detected. The decrease in ablation zones' volume was
significantly larger (p < 0.05 for all time intervals) after IRE (arterial phase,
7.5%; venous phase, 9.7% of initial volume) compared to RFA (arterial phase,
39.6%; venous phase, 45.3% of initial volume). After RFA, significantly smaller
decreases in the ablation volumes, in general, were detected in patients treated
with PCT in their history (p = 0.004), which was not detected after IRE (p =
0.288). In the arterial phase, peripheral rim enhancement was frequently detected
after both IRE and RFA. In the venous phase, rim-enhancement was depicted
significantly more often following IRE at t1 and t2 (pt1 = 0.003, pt2 < 0.001).
Conclusion: As per our analysis, ablation zone volume decreased significantly in
a more rapid and more profound manner after IRE. Lesion's remodeling after RFA
but not IRE seems to be influenced by PCT, possibly due to the type of cell death
induced by the different ablation modalities.
PMID- 29962863
TI - The Diagnostic Performance of Liver MRI without Intravenous Contrast for
Detecting Hepatocellular Carcinoma: A Case-Controlled Feasibility Study.
AB - Objective: To preliminarily evaluate the diagnostic performance of an unenhanced
MRI for detecting hepatocellular carcinoma (HCC) with a case-control study
design. Materials and Methods: The case group consisted of 175 patients with
initially-diagnosed HCC, who underwent a 3T liver MRI. A total of 237 HCCs were
identified. The number of HCCs that were smaller than 1 cm, 1 cm <= and < 2 cm,
and >= 2 cm were 19, 105, and 113, respectively. For the control group, 72
patients with chronic liver disease, who did not have HCC, were enrolled. Two
radiologists independently reviewed the T2 half-Fourier acquisition single-shot
turbo spin echo, T2 fast spin echos with fat saturation, T1 gradient in- and out
of-phase images, and diffusion-weighted images/apparent diffusion coefficient
maps to detect HCC. Per-patient analyses were performed to evaluate the
sensitivity and specificity of the non-contrast MRI for diagnosing HCC.
Furthermore, the per-lesion sensitivity was also calculated according to tumor
size. Results: In the per-patient analyses, the sensitivity and specificity of
reader 1 were 86.3% (151/175) and 87.5% (63/72), respectively; while those of
reader 2 were 82.9% (145/175) and 76.4% (55/72), respectively. When excluding
HCCs smaller than 1 cm, the sensitivity of reader 1 and 2 were 88.0% (147/167)
and 86.2% (144/167), respectively. In the per-lesion analyses, the sensitivities
of reader 1 and reader 2 were 75.9% (180/237) and 70.5% (167/237), respectively.
Conclusion: The per-patient sensitivity and specificity of non-contrast MRIs were
within a reasonable range for the initial diagnosis of HCC. Non-contrast MRIs may
have a potential for surveillance of HCC. Further confirmatory diagnostic test
accuracy studies are needed.
PMID- 29962864
TI - Optimal Monochromatic Imaging of Spectral Computed Tomography Potentially
Improves the Quality of Hepatic Vascular Imaging.
AB - Objective: To investigate the efficiency of spectral computed tomography (CT)
optimal monochromatic images in improving imaging quality of liver vessels.
Materials and Methods: The imaging data of 35 patients with abdominal CT
angiography were retrospectively analyzed. Hepatic arteries, portal veins, and
hepatic veins were reconstructed with mixed energy (quality check, QC), 70 keV
and optimal monochromatic mode. Comparative parameters were analyzed including CT
value, image noise (IN), contrast-to-noise ratio (CNR), signal-to-noise ratio
(SNR), and subjective qualitative analysis. Results: The optimal monochromatic
value for assessment of the common hepatic artery, portal vein, and hepatic vein
ranged between 49 keV and 53 keV, with a mean of 51 keV. There were statistically
significant differences (p < 0.001) among the optimal monochromatic, 70 keV and
QC images with regards to the hepatic vascular CT value, IN, CNR, SNR, and
subjective qualitative score. CNR of the common hepatic artery in the optimal
monochromatic, 70 keV and QC groups was 24.6 +/- 10.9, 18.1 +/- 8.3, and 11.6 +/-
4.6, respectively (p < 0.001) with subjective scores of 4.7 +/- 0.2, 4.0 +/- 0.3,
and 3.6 +/- 0.4, respectively (p < 0.001). CNR of the hepatic portal vein was 6.9
+/- 2.7, 4.3 +/- 1.9, and 3.0 +/- 2.1, respectively (p < 0.001) with subjective
scores of 4.5 +/- 0.3, 3.9 +/- 0.4, and 3.3 +/- 0.3, respectively (p < 0.001).
CNR of the hepatic vein was 5.7 +/- 2.3, 4.2 +/- 1.9, and 2.7 +/- 1.4,
respectively with subjective scores of 4.3 +/- 0.3, 3.8 +/- 0.4, and 3.2 +/- 0.3,
respectively (p < 0.001). Conclusion: Optimal monochromatic images can lead to
improvement in the imaging parameters and optimization of the image quality of
the common hepatic artery, hepatic portal vein and hepatic vein compared with
conventional mixed kV and with 70 keV datasets.
PMID- 29962865
TI - Recent Update of Embolization of Postpartum Hemorrhage.
AB - Postpartum hemorrhage (PPH) is a life-threatening condition and remains a leading
cause of maternal mortality. Transcatheter arterial embolization (TAE) is an
effective therapeutic strategy for PPH with the advantages of fast speed,
repeatability, and the possibility of fertility preservation. We reviewed the
vascular anatomy relevant to PPH, the practical details of TAE emphasizing the
timing of embolization, and various clinical conditions of PPH according to a
recent literature review.
PMID- 29962866
TI - Percutaneous Metallic Stent Placement for Palliative Management of Malignant
Biliary Hilar Obstruction.
AB - Objective: To investigate the outcomes of percutaneous metallic stent placements
in patients with malignant biliary hilar obstruction (MBHO). Materials and
Methods: From January 2007 to December 2014, 415 patients (mean age, 65 years;
261 men [62.8%]) with MBHO were retrospectively studied. All the patients
underwent unilateral or bilateral stenting in a T, Y, or crisscross configuration
utilizing covered or uncovered stents. The clinical outcomes evaluated were
technical and clinical success, complications, overall survival rates, and stent
occlusion-free survival. Results: A total of 784 stents were successfully placed
in 415 patients. Fifty-five patients had complications. These complications
included hemobilia (n = 19), cholangitis (n = 13), cholecystitis (n = 11),
bilomas (n = 10), peritonitis (n = 1), and hepatic vein-biliary fistula (n = 1).
Clinical success was achieved in 370 patients (89.1%). Ninety-seven patients were
lost to follow-up. Stent dysfunction due to tumor ingrowth (n = 107), sludge
incrustation (n = 44), and other causes (n = 3) occurred in 154 of 318 patients.
The median overall survival and the stent occlusion-free survival were 212 days
(95% confidence interval [CI], 186-237 days) and 141 days (95% CI, 126-156 days),
respectively. The stent type and its configuration did not affect technical
success, complications, successful internal drainage, overall survival, or stent
occlusion-free survival. Conclusion: Percutaneous stent placement may be safe and
effective for internal drainage in patients with MBHO. Furthermore, stent type
and configuration may not significantly affect clinical outcomes.
PMID- 29962867
TI - A Prospective Randomized Comparison of a Covered Metallic Ureteral Stent and a
Double-J Stent for Malignant Ureteral Obstruction.
AB - Objective: To compare the safety and efficacy between a covered metallic ureteral
stent (CMS) and a double-J ureteral stent (DJS) for the treatment of a malignant
ureteral obstruction (MUO). Materials and Methods: Nineteen patients (seven men
and 12 women; mean age, 53.4 years) were randomly assigned to the CMS (n = 10) or
DJS (n = 9) group. The following were compared between the two groups: technical
success, i.e., successful stent placement into desired locations; stent
malfunction; stent patency, i.e., no obstruction and no additional intervention;
complications; and patient survival. Results: The technical success rate was 100%
in all 10 and 12 ureteral units in the CMS and DJS groups, respectively. During
the mean follow-up period of 253.9 days (range, 63-655 days), stent malfunction
was observed in 40.0% (4/10) and 66.7% (8/12) in the CMS and DJS groups,
respectively. In the per-ureteral analysis, the median patency time was 239.0
days and 80.0 days in the CMS and DJS groups, respectively. The CMS group yielded
higher patency rates compared with the DJS group at three months (90% vs. 35%)
and at six months (57% vs. 21%). The overall patency rates were significantly
higher in the CMS group (p = 0.041). Complications included the migration of two
metallic stents in one patient in the CMS group, which were removed in a
retrograde manner. The two patient groups did not differ significantly regarding
their overall survival rates (p = 0.286). Conclusion: Covered metallic ureteral
stent may be effective for MUO.
PMID- 29962868
TI - Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization
Therapy Versus Surgical Resection for Hepatocellular Carcinoma within the Milan
Criteria: A Meta-Analysis.
AB - Objective: To meta-analytically compare combined transarterial chemoembolization
(TACE) plus radiofrequency ablation (RFA) and surgical resection (SR) for the
treatment of hepatocellular carcinoma (HCC) within the Milan criteria. Materials
and Methods: PubMed, Medline, Embase, and Cochrane Library were searched for
studies comparing these two therapies that were published between January 2006
and August 2017. Overall survival rate (OS), recurrence-free survival rate (RFS),
major complications and the average length of hospital stay were compared between
these two therapies. Meta-analytic pooled odds ratio (OR) was calculated using
TACE plus RFA as the base category. Results: Seven case-control studies and one
randomized trial were identified. Meta-analytic results revealed that, compared
with SR, TACE plus RFA had significantly higher 1-year OS (OR for survival =
0.50, p = 0.009) and lower major complications (OR = 1.88, p = 0.02) after
therapy. Three studies reported on the length of hospital stay. The average
length +/- standard deviation reported in individual studies for SR and TACE plus
RFA groups was 19.8 +/- 8.4 days and 7.4 +/- 2.2 days, respectively; 18.7 +/- 4.9
days and 11.5 +/- 6.9 days, respectively; and 16.6 +/- 6.7 days and 8.5 +/- 4.1
days, respectively (p < 0.0001 for all studies). Three or 5-year OS and 1-, 3-,
or 5-year RFS did not significantly differ between the two therapies. Conclusion:
Combined TACE plus RFA may be an alternative to SR for the treatment of patients
with HCC within Milan the criteria. Non-randomized design in most of the original
studies was a limitation.
PMID- 29962869
TI - Primary Imaging Test and Appropriate Biopsy Methods for Thyroid Nodules:
Guidelines by Korean Society of Radiology and National Evidence-Based Healthcare
Collaborating Agency.
AB - The Korean Society of Radiology and the National Evidence-based Healthcare
Collaborating Agency developed guidelines for primary imaging tests and
appropriate biopsy methods for thyroid nodules. These guidelines were developed
using an adaptation process by collaboration between the development committee
and the working group. The development committee, composed of research
methodology experts, established the overall plan and provided support about
methodological strategies. The working group, composed of radiologist experts in
thyroid imaging, wrote the proposals. The guidelines recommend neck ultrasound
(US) as a first-line imaging modality for the diagnosis of thyroid nodules in
patients with suspected nodules, and US-guided fine-needle aspiration as a
primary method for histologic examination of thyroid nodules.
PMID- 29962871
TI - Evaluation of Modified Core-Needle Biopsy in the Diagnosis of Thyroid Nodules.
AB - Objective: Core needle biopsy (CNB) of the thyroid is an additional diagnostic
method for non-diagnostic or indeterminate cytology samples. We sought to
evaluate a new modified core biopsy technique and compare the concordance of its
diagnosis with the final diagnosis of the surgically resected specimen. Materials
and Methods: A retrospective analysis was conducted on 842 patients who had a
thyroid CNB with or without a previous fine-needle aspiration from August 2002 to
March 2015; 38% of patients ultimately underwent thyroidectomy. We divided the
patients into two groups for comparison: conventional group (n = 329) and new
modified technique group (n = 513) that enabled sampling of not only the lesion
but also the margin and surrounding parenchyma. The diagnostic conclusiveness of
CNB and concordant rate with thyroidectomy was compared between the two groups.
Results: The overall diagnostic conclusiveness did not exhibit a significant
increase (77% in the conventional technique group and 75% in the modified
technique group, p = 0.408). In terms of the diagnostic concordance rate between
CNB and thyroidectomy, no overall significant increase was observed (83% in the
conventional technique group and 88% in the modified technique group, p = 0.194).
However, only in follicular-patterned lesions (nodular hyperplasia, follicular
neoplasm, and follicular variant of papillary thyroid carcinoma), a significant
increase in the diagnostic concordance rate was observed (83% in the conventional
group and 94% in the modified technique group, p = 0.033). Conclusion: Modified
CNB technique can be beneficial for the accurate diagnosis of follicular
patterned thyroid lesions.
PMID- 29962872
TI - Computer-Aided Diagnosis of Thyroid Nodules via Ultrasonography: Initial Clinical
Experience.
AB - Objective: To prospectively evaluate the diagnostic performance of computer-aided
diagnosis (CAD) for detection of thyroid cancers via ultrasonography (US).
Materials and Methods: This study included 50 consecutive patients with 117
thyroid nodules on US during the period between June 2016 and July 2016. A
radiologist performed US examinations using real-time CAD integrated into a US
scanner. We compared the diagnostic performance of radiologist, the CAD system,
and the CAD-assisted radiologist for the detection of thyroid cancers. Results:
The sensitivity, specificity, positive predictive value (PPV), negative
predictive value (NPV), and accuracy of the CAD system were 80.0, 88.1, 83.3,
85.5, and 84.6%, respectively, and were not significantly different from those of
the radiologist (p > 0.05). The CAD-assisted radiologist showed improved
diagnostic sensitivity compared with the radiologist alone (92.0% vs. 84.0%, p =
0.037), while the specificity and PPV were reduced (85.1% vs. 95.5%, p = 0.005
and 82.1% vs. 93.3%, p = 0.008). The radiologist assisted by the CAD system
exhibited better diagnostic sensitivity and NPV than the CAD system alone (92.0%
vs. 80.0%, p = 0.009 and 93.4% vs. 88.9%, p = 0.013), while the specificities and
PPVs were not significantly different (88.1% vs. 85.1%, p = 0.151 and 83.3% vs.
82.1%, p = 0.613, respectively). Conclusion: The CAD system may be an adjunct to
radiological intervention in the diagnosis of thyroid cancer.
PMID- 29962873
TI - Ultrasonographic Echogenicity and Histopathologic Correlation of Thyroid Nodules
in Core Needle Biopsy Specimens.
AB - Objective: To determine the histopathologic features associated with
ultrasonographic echogenicity of thyroid nodules. Materials and Methods: This
study included 95 nodules of 95 patients (76 women, 19 men; mean age 47.5 +/-
12.9 years) with homogeneous echogenicity in which core needle biopsy was
performed during a one year period. The nodule echogenicity was categorized into
4 grades (hyperechogenicity, isoechogenicity, mild hypoechogenicity, and marked
hypoechogenicity). The biopsy specimens were evaluated by a pathologist regarding
the histopathologic features of fibrosis, lymphoid infiltration, microfollicular
pattern, uniform follicular pattern, and hypercellularity in nodules. We
evaluated the association of each histopathologic feature among 3 categories of
nodule echogenicity by multinomial regression analysis. Results: The nodule
echogenicity was isoechoic in 28 (29.5%), mildly hypoechoic in 37 (38.9%), and
markedly hypoechoic in 30 (31.6%), and there was no hyperechoic nodule. There was
a trend of increasing frequency of fibrosis (> 30%) as nodule echogenicity
decreased (isoechogenicity, 10.7%; mild hypoechogenicity, 32.4%; and marked
hypoechogenicity, 80%; p < 0.001). The microfollicular pattern, uniform
follicular pattern, and hypercellularity were frequently found in mildly
hypoechoic nodules than in isoechoic nodules (p <= 0.018). The fibrosis (> 30%)
and hypercellularity were independently associated with mild or marked
hypoechogenicity as compared to isoechogenicity (fibrosis; p <= 0.004 and
hypercellularity; p <= 0.036), and only fibrosis (> 30%) was independently
associated with marked hypoechogenicity as compared to mild hypoechogenicity (p =
0.004). Conclusion: The fibrosis (> 30%) and high cellularity are independently
associated with mild or marked hypoechogenicity of nodules. The knowledge of the
relationship of echogenicity and histopathology of thyroid nodules could improve
management of patients with thyroid nodules.
PMID- 29962870
TI - 2017 Thyroid Radiofrequency Ablation Guideline: Korean Society of Thyroid
Radiology.
AB - Thermal ablation using radiofrequency is a new, minimally invasive modality
employed as an alternative to surgery in patients with benign thyroid nodules and
recurrent thyroid cancers. The Task Force Committee of the Korean Society of
Thyroid Radiology (KSThR) developed recommendations for the optimal use of
radiofrequency ablation for thyroid tumors in 2012. As new meaningful evidences
have accumulated, KSThR decided to revise the guidelines. The revised guideline
is based on a comprehensive analysis of the current literature and expert
consensus.
PMID- 29962874
TI - Early Prediction of Response to Neoadjuvant Chemotherapy Using Dynamic Contrast
Enhanced MRI and Ultrasound in Breast Cancer.
AB - Objective: To determine the diagnostic performance of dynamic contrast-enhanced
magnetic resonance imaging (DCE-MRI) and DCE ultrasound (DCE-US) for predicting
response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials
and Methods: This Institutional Review Board-approved prospective study was
performed between 2014 and 2016. Thirty-nine women with breast cancer underwent
DCE-US and DCE-MRI before the NAC, follow-up DCE-US after the first cycle of NAC,
and follow-up DCE-MRI after the second cycle of NAC. DCE-MRI parameters (transfer
constant [Ktrans], reverse constant [kep], and leakage space [Ve]) were assessed
with histograms. From DCE-US, peak-enhancement, the area under the curve, wash-in
rate, wash-out rate, time to peak, and rise time (RT) were obtained. After
surgery, all the imaging parameters and their changes were compared with
histopathologic response using the Miller-Payne Grading (MPG) system. Data from
minor and good responders were compared using Wilcoxon rank sum test, chi-square
test, or Fisher's exact test. Receiver operating characteristic curve analysis
was used for assessing diagnostic performance to predict good response. Results:
Twelve patients (30.8%) showed a good response (MPG 4 or 5) and 27 (69.2%) showed
a minor response (MPG 1-3). The mean, 25th, 50th, and 75th percentiles of Ktrans
and Kep of post-NAC DCE-MRI differed between the two groups. These parameters
showed fair to good diagnostic performance for the prediction of response to NAC
(AUC 0.76-0.81, p <= 0.007). Among DCE-US parameters, the percentage change in RT
showed fair prediction (AUC 0.71, p = 0.023). Conclusion: Quantitative analysis
of DCE-MRI and DCE-US was helpful for early prediction of response to NAC.
PMID- 29962875
TI - Is It Better to Enter a Volume CT Dose Index Value before or after Scan Range
Adjustment for Radiation Dose Optimization of Pediatric Cardiothoracic CT with
Tube Current Modulation?
AB - Objective: To determine whether the body size-adapted volume computed tomography
(CT) dose index (CTDvol) in pediatric cardiothoracic CT with tube current
modulation is better to be entered before or after scan range adjustment for
radiation dose optimization. Materials and Methods: In 83 patients,
cardiothoracic CT with tube current modulation was performed with the body size
adapted CTDIvol entered after (group 1, n = 42) or before (group 2, n = 41) scan
range adjustment. Patient-related, radiation dose, and image quality parameters
were compared and correlated between the two groups. Results: The CTDIvol after
the CT scan in group 1 was significantly higher than that in group 2 (1.7 +/- 0.1
mGy vs. 1.4 +/- 0.3 mGy; p < 0.0001). Image noise (4.6 +/- 0.5 Hounsfield units
[HU] vs. 4.5 +/- 0.7 HU) and image quality (1.5 +/- 0.6 vs. 1.5 +/- 0.6) showed
no significant differences between the two (p > 0.05). In both groups, all
patient-related parameters, except body density, showed positive correlations (r
= 0.49-0.94; p < 0.01) with the CTDIvol before and after the CT scan. The CTDIvol
after CT scan showed modest positive correlation (r = 0.49; p <= 0.001) with
image noise in group 1 but no significant correlation (p > 0.05) in group 2.
Conclusion: In pediatric cardiothoracic CT with tube current modulation, the
CTDIvol entered before scan range adjustment provides a significant dose
reduction (18%) with comparable image quality compared with that entered after
scan range adjustment.
PMID- 29962876
TI - Comparison between Three-Dimensional Navigator-Gated Whole-Heart MRI and Two
Dimensional Cine MRI in Quantifying Ventricular Volumes.
AB - Objective: To test whether the method utilizing three-dimensional (3D) whole
heart MRI has an additional benefit over that utilizing conventional two
dimensional (2D) cine MRI in quantifying ventricular volumes. Materials and
Methods: In 110 patients with congenital heart disease, a navigator-gated, 3D
whole-heart MRI during end-systole (ES) and end-diastole (ED), 2D short-axis cine
MRI, and phase contrast MRI of the great arteries were acquired. Ventricular
volumes were measured by using a 3D threshold-based segmentation for 3D whole
heart MRI and by using a simplified contouring for 2D cine MRI. The cardiac
trigger delays of 3D whole-heart MRI were compared with those of a 2D cine MRI.
The stroke volumes calculated from the ventricular volumes were compared with the
arterial flow volumes, measured by phase contrast MRI. Results: The ES and ED
trigger delays of whole-heart MRI were significantly less than cine MRI for both
the left ventricle (-16.8 +/- 35.9 ms for ES, -59.0 +/- 90.4 ms for ED; p <
0.001) and the right ventricle (-58.8 +/- 30.6 ms for ES, -104.9 +/- 92.7 ms for
ED; p < 0.001). Compared with the arterial flow volumes, 2D cine MRI
significantly overestimated the left ventricular stroke volumes (8.7 +/- 8.9 mL,
p < 0.001) and the 3D whole-heart MRI significantly underestimated the right
ventricular stroke volumes (-22.7 +/- 22.9 mL, p < 0.001). Conclusion: Three
dimensional whole-heart MRI is often subject to early timing of the ED phase,
potentially leading to the underestimation of the right ventricular stroke
volumes.
PMID- 29962877
TI - Association between Magnetic Resonance Imaging Findings of the Pelvic Floor and
de novo Stress Urinary Incontinence after Vaginal Delivery.
AB - Objective: The study aimed to evaluate the contributions of levator ani muscle
(LAM) injury, vesical neck movement, urethral length and mobility, and urethral
sphincter dysfunction observed on magnetic resonance imaging (MRI) towards stress
urinary incontinence (SUI) after vaginal delivery. Materials and Methods: Fifty
primiparous women after 6 months of delivery (15 with SUI and 35 without) and 35
nulliparous as continent controls underwent MRI at rest and Valsalva maneuver. A
published levator ani scoring system was used to characterize morphological
changes of LAM. The severity of the injury was divided into three categories as
none, minor, and major. A series of common parameters including levator plate
angle, iliococcygeal angle, and levator hiatus were used to describe the
functional conditions of LAM. Urethral mobility was defined based on the rotation
of the urethra between Valsalva and rest status. Vesical neck movement was
evaluated by its distance to the pubococcygeal line. Urethral sphincter
dysfunction was defined as the widening of the proximal urethra and/or funneling
at the urethrovesical junction during Valsalva. Results: Primiparous incontinent
(PI) women had additional major levator ani defects (33.3% vs. 17.1%) while less
minor defects (0.7% vs. 31.4%) than primiparous continent (PC) women. Vesical
neck downward movement in PI women was more obvious than PC women (28.5 mm vs.
24.2 mm, p = 0.006). Urethral mobility was more active in primiparous women than
in nulliparous continent controls (57.4 vs. 52.4), whereas no difference was
observed on urethral mobility in the primiparous group (p = 0.25). Urethral
sphincter dysfunction and funneling were present in 80% of PI women versus 22.9%
in PC women (p < 0.001). Conclusion: The MRI findings revealed that de novo SUI
was associated with major LAM injury, vesical neck downward movement as well as
urethral sphincter dysfunction. Vesical neck funneling on sagittal images can be
treated as a valuable predictor for SUI. The intervention for the PI should focus
on the elevation of vesical neck, rehabilitation of LAM as well as recovery of
the urethral sphincter muscle.
PMID- 29962878
TI - Efficacy, Efficiency, and Safety of Magnetic Resonance-Guided High-Intensity
Focused Ultrasound for Ablation of Uterine Fibroids: Comparison with Ultrasound
Guided Method.
AB - Objective: The purpose of this study was to compare efficacy, sonication energy
efficiency, treatment time and safety of magnetic resonance-guided high-intensity
focused ultrasound (MRgHIFU) and those of ultrasound-guided high-intensity
focused ultrasound (USgHIFU) for ablation of uterine fibroids. Materials and
Methods: This study included 43 patients with 44 symptomatic uterine fibroids
treated with MRgHIFU and 51 patients with 68 symptomatic uterine fibroids treated
with USgHIFU. After therapy, contrast-enhanced MRI was conducted and complete
ablation was defined as 100% non-perfused volume (NPV) of fibroids. Patients with
completely ablated fibroids were selected for the comparison of the treatment
data and sonication parameters between MRgHIFU and USgHIFU treated groups.
Results: Thirteen completely ablated fibroids in 10 patients (23.3%, 10/43) were
achieved with MRgHIFU and 28 completely ablated fibroids in 22 patients (43.1%,
22/51) were achieved with USgHIFU. In completely ablated fibroids, the energy
efficiency factor (EEF) was 5.1 +/- 3.0 J/mm3 and 4.7 +/- 2.5 J/mm3 in the
MRgHIFU and USgHIFU, respectively (p = 0.165). There was a negative linear
correlation between EEF and the NPV of fibroids for MRgHIFU (p = 0.016) and
USgHIFU (p = 0.001). The mean treatment time was 174.5 +/- 42.2 minutes and 114.4
+/- 39.2 minutes in the MRgHIFU and USgHIFU procedures, respectively (p = 0.021).
There were no severe adverse events and major complications after treatment.
Conclusion: MRgHIFU and USgHIFU are safe and effective with the equivalent energy
efficiency for complete ablation of fibroids. USgHIFU has shorter treatment time
than MRgHIFU.
PMID- 29962879
TI - Yield of Repeat Targeted Direct in-Bore Magnetic Resonance-Guided Prostate Biopsy
(MRGB) of the Same Lesions in Men Having a Prior Negative Targeted MRGB.
AB - Objective: This study's purposes were to determine the yield of repeat direct in
bore magnetic resonance-guided prostate biopsy (MRGB) (MRGB-2) after the first
one was found to be negative (MRGB-1), to correlate with clinical parameters, and
to present the subgroup analyses of patients with positive repeat biopsies,
despite having a negative initial biopsies. Materials and Methods: We
retrospectively included patients with MRGB-2 after a negative MRGB-1 both
between January 2006 and August 2016. This study included 62 patients (median
age, 63 years; interquartile range [IQR], 58-66 years) with 75 sampled lesions
during MRGB-2 left for analysis, and 63 lesions were resampled and 12 new lesions
were sampled. Included patients had a prostate specific antigen (PSA) at MRGB-1
of 13 ng/mL (IQR, 5.8-20.0) and a PSA at MRGB-2 of 15 ng/mL (IQR, 9.0-22.5). All
anonymized magnetic resonance imaging (MRI) data were retrospectively reassessed
according to Prostate Imaging-Reporting and Data System version 2 by two
radiologists. Images of MRGB were compared to determine whether the same prostate
lesion was biopsied during MRGB-1 and MRGB-2. Descriptive statistics were
utilized to determine the yield of clinically significant prostate cancer (csPCa)
at MRGB-2. Gleason score of >= 3 + 4 was considered csPCa. Results: In 16/75
(21%) lesions csPCa was detected during MRGB-2. Of 63 resampled lesions, 13 (21%)
harbored csPCa at MRGB-2. In two patients, csPCa was detected on repeat biopsy,
while the volume of the lesion decreased between MRGB-1 and MRGB-2. Conclusion:
Patients could benefit from repeat biopsy after negative initial MRGB, especially
in the case of increasing PSA values and persisting PCa suspicion in MRI. Further
research is needed to establish predictors for positive repeat targeted biopsies.
PMID- 29962880
TI - Secondary Tumors of the Urinary System: An Imaging Conundrum.
AB - Imaging features of metastases to the urinary system may closely mimic primary
urinary tract tumors, and differential diagnosis by imaging alone may be
problematic or even impossible in some cases. The main purpose of this article
was to familiarize radiologists with imaging findings of metastasis to the
urinary system on cross-sectional imaging, with an emphasis on abdominal and
pelvic computed tomography and magnetic resonance imaging. In addition, we review
the clinical importance and implications of metastases to the urinary tract and
provide information on diagnostic work-ups.
PMID- 29962881
TI - Ultrasonographic Findings of Subcutaneous Angioleiomyomas in the Extremities
Based on Pathologic Subtypes.
AB - Objective: The purpose of this study was to describe the ultrasonographic
findings of angioleiomyoma based on pathological subtypes. Materials and Methods:
Thirty-nine patients with subcutaneous angioleiomyomas in the extremities were
retrospectively reviewed by two radiologists and a pathologist. Sonographic
images were analyzed to evaluate each tumor's anatomic location, size, shape,
margin, heterogeneity, echogenicity, associated findings, and vascularity.
Results: Angioleiomyomas were divided into 3 subtypes: capillary (n = 16), venous
(n = 22), and cavernous (n = 1). The one cavernous angioleiomyoma was a
hypoechoic mass with rich vascularity. Hypoechogenicity was more frequently
observed for venous tumors (77.3%) than for capillary tumors (43.8%), and
isoechogenicity was more frequently observed for capillary tumors (56.2%) than
for venous tumors (22.7%). Moderate vascularity was more frequently observed for
venous tumors (59.1%) than for capillary tumors (12.5%), and little vascularity
was more frequently observed for capillary tumors (62.5%) than for venous tumors
(13.6%). The aforementioned findings including echogenicity (p = 0.034) and
vascularity (p = 0.003) were statistically significant. Conclusion: Awareness of
sonographic findings of angioleiomyomas based on pathologic subtypes could be
helpful for diagnosing angioleiomyoma and could increase diagnostic accuracy for
superficial soft-tissue masses in our practice.
PMID- 29962882
TI - Evaluation of Salivary Gland Function Using Diffusion-Weighted Magnetic Resonance
Imaging for Follow-Up of Radiation-Induced Xerostomia.
AB - Objective: To investigate the value of diffusion-weighted magnetic resonance
imaging (DW-MRI) as a noninvasive tool to assess salivary gland function for
follow-up of patients with radiation-induced xerostomia. Materials and Methods:
This study included 23 patients with nasopharyngeal carcinoma who had been
treated with parotid-sparing radiotherapy (RT). Salivary function was assessed by
DW-MRI pre-treatment and one week and one year post-RT, respectively. The maximum
apparent diffusion coefficient (ADC) of parotid glands (pADCmax) and the time to
peak ADC of parotid glands (pTmax) during stimulation were obtained. Multivariate
analysis was used to analyze factors correlated with the severity of radiation
induced xerostomia. Results: The ADCs of parotid and submandibular glands (1.26
+/- 0.10 * 10-3 mm2/s and 1.32 +/- 0.07 * 10-3 mm2/s pre-RT, respectively) both
showed an increase in all patients at one week post-RT (1.75 +/- 0.16 * 10-3
mm2/s, p < 0.001 and 1.70 +/- 0.16 * 10-3 mm2/s, p < 0.001, respectively),
followed by a decrease in parotid glands at one year post-RT(1.57 +/- 0.15 * 10-3
mm2/s, p < 0.001) but not in submandibular glands (1.69 +/- 0.18 * 10-3 mm2/s, p
= 0.581). An improvement in xerostomia was found in 13 patients at one year post
RT. Multivariate analysis revealed 4 significant predictors for the improvement
of xerostomia, including dose to parotid glands (p = 0.009, odds ratio [OR] =
0.639), the ADC of submandibular glands (p = 0.013, OR = 3.295), pADCmax (p =
0.024, OR = 0.474), and pTmax (p = 0.017, OR = 0.729) at one week post-RT.
Conclusion: The ADC value is a sensitive indicator for salivary gland
dysfunction. DW-MRI is potentially useful for noninvasively predicting the
severity of radiation-induced xerostomia.
PMID- 29962883
TI - Migraine with Aura: Surface-Based Analysis of the Cerebral Cortex with Magnetic
Resonance Imaging.
AB - Objective: Previous migraine studies have reported gray matter alterations in
various cortical regions with conflicting results. This study aimed to explore a
cortical morphometric difference in migraineurs with aura (MA) compared to
healthy subjects (HS) and to delineate a possible difference between the cortical
morphological features and different aura phenotypes. Materials and Methods:
Forty-eight MA and 30 HS that were balanced by sex, age, and educational level
were selected for this study. T2-weighted and three-dimensional T1-weighted
magnetic resonance imaging (MRI) of the brain were acquired using a 1.5T MRI
scanner. Surface-based morphometry from the MRI data was used to identify
differences between the MA and HS group, and then between MA subgroups. The MA
group was subdivided into migraineurs who experienced only visual aura (MVA) and
migraineurs who had visual, somatosensory and dysphasic symptoms (MVA+). Results:
The MVA+ group had significantly reduced cortical surface area of the left
rostral middle frontal cortex compared with the MVA group (p < 0.001). Migraine
patients had significantly reduced volume of the left fusiform gyrus relative to
HS (p < 0.001). Also, the sulcal depth increased at the level of the left
temporal pole in the MVA+ group relative to the MVA group (p < 0.001). The vertex
by-vertex analysis did not exhibit any significant difference in cortical
thickness between MA and HS, and between MVA+ and MVA, when corrected for
multiple comparisons. Conclusion: Migraineurs with aura demonstrates different
morphometric features from HS in multiple cortical regions. MVA+ have different
morphometric features in the left frontal and temporal lobe relative to MVA,
which could be a source of distinct symptoms and serve as potential biomarkers of
different MA subtypes.
PMID- 29962884
TI - Inter-Vendor and Inter-Session Reliability of Diffusion Tensor Imaging:
Implications for Multicenter Clinical Imaging Studies.
AB - Objective: To evaluate the inter-vendor and inter-session reliability of
diffusion tensor imaging (DTI) and relevant parameters. Materials and Methods:
This prospective study included 10 healthy subjects (5 women and 5 men; age
range, 25-33 years). Each subject was scanned twice using 3T magnetic resonance
scanners from three different vendors at two different sites. A voxel-wise
statistical analysis of diffusion data was performed using Tract-Based Spatial
Statistics. Fractional anisotropy (FA), mean diffusivity (MD), and radial
diffusivity (RD) values were calculated for each brain voxel using FMRIB's
Diffusion Toolbox. Results: A repeated measures analysis of variance revealed
that there were no significant differences in FA values across the vendors or
between sessions; however, there were significant differences in MD values
between the vendors (p = 0.020). Although there were no significant differences
in inter-session MD and inter-session/inter-vendor RD values, a significant group
* factor interaction revealed differences in MD and RD values between the 1st and
2nd sessions conducted by the vendors (p = 0.004 and 0.006, respectively).
Conclusion: Although FA values exhibited good inter-vendor and inter-session
reliability, MD and RD values did not show consistent results. Researchers using
DTI should be aware of these limitations, especially when implementing DTI in
multicenter studies.
PMID- 29962885
TI - Application of Synthetic MRI for Direct Measurement of Magnetic Resonance
Relaxation Time and Tumor Volume at Multiple Time Points after Contrast
Administration: Preliminary Results in Patients with Brain Metastasis.
AB - Objective: The purpose of this study was to investigate the time-dependent
effects of contrast medium on multi-dynamic, multi-echo (MDME) sequence in
patients with brain metastases. Materials and Methods: This study included 7
patients with 15 brain metastases who underwent magnetic resonance (MR)
examination which included MDME sequences at 1 minute, 10 minutes and 20 minutes
after contrast injection. Two volumes of interests, covering an entire tumor
(whole tumor) and the enhancing portion of the tumor, were derived from post
contrast synthetic T1-weighted images. Statistical comparisons were performed for
three different time delays for histogram parameters of the longitudinal
relaxation rate (R1) and the transverse relaxation rate (R2), and lesion volumes.
Results: The mean and the median of R1 and the mean of R2 in both the whole tumor
and the inner enhancing portion were larger on the 10 minutes delayed images than
on the 1 minute or 20 minutes delayed images (mean of R1 in the whole tumor on
the 1 minute, 10 minutes, and 20 minutes delayed images: 1.26 ms, 1.39 ms, and
1.37 ms; mean of R1 in the inner enhancing portion: 1.43 ms, 1.53 ms and 1.44 ms;
all p < 0.017). The volumes of the whole tumor and the inner enhancing portion
were significantly larger in the 10 minutes and 20 minutes delayed images than on
the 1 minute delayed images (all p < 0.017). Conclusion: Magnetic resonance
relaxation times and the volumes of the whole tumor and the inner enhancing
portion were measured larger on the 10 minutes or 20 minutes delayed images than
on the 1 minute delayed images. The MDME sequence immediately after contrast
injection cannot fully reflect the effects of gadolinium-based contrast agent
leakage in the tissue.
PMID- 29962886
TI - Pulmonary Artery Intimal Sarcoma versus Pulmonary Artery Thromboembolism: CT and
Clinical Findings.
AB - Objective: To describe CT and clinical findings of pulmonary artery intimal
sarcoma (PAIS) compared with those of pulmonary thromboembolism (PTE), to
investigate MRI and positron emission tomography (PET)-CT findings of PAIS, and
to evaluate the effect of delayed diagnosis of PAIS on survival outcomes.
Materials and Methods: Twenty-six patients with PAIS were retrospectively
identified and matched for sex, with patients with PTE at a ratio of 1:2. CT and
clinical findings of the two groups were compared using Student's t test or chi
square test. The effect of delayed diagnosis on survival was investigated using
Kaplan-Meier analysis. Results: The most common tumor pattern in PAIS was tumoral
impaction. Heterogeneous attenuation, wall eclipse signs, intratumoral vessels,
acute interphase angles, single location, presence of lung ischemia, and central
location were significantly more common in PAIS than in PTE (all p < 0.01).
Levels of D-dimers and brain natriuretic peptide were lower in PAIS than in PTE
(p < 0.05). In three patients of PAIS, long inversion time sequence MRI showed
intermingled dark signal intensity foci suggestive of intermingled thrombi. All
nine patients who had undergone PET-CT displayed hypermetabolism. Diagnosis was
delayed in 42.3% of the PAIS patients and those patients had a significantly
shorter overall survival than patients whose diagnosis was not delayed (p <
0.05). Conclusion: The characteristic CT and clinical findings of PAIS may help
achieve early diagnosis of PAIS and make better survival outcomes of patients.
MRI and PET-CT can be used as second-line imaging modalities and could help
distinguish PAIS from PTE and to plan clinical management.
PMID- 29962887
TI - Radiological Report of Pilot Study for the Korean Lung Cancer Screening (K-LUCAS)
Project: Feasibility of Implementing Lung Imaging Reporting and Data System.
AB - Objective: To report the radiological results of a pilot study for the Korean
Lung Cancer Screening project conducted to evaluate the feasibility of lung
cancer screening using low-dose chest computed tomography (LDCT) in Korea.
Materials and Methods: The National Cancer Center and three regional cancer
centers participated in this study. Asymptomatic current or ex-smokers aged 55-74
years with a smoking history of at least 30 pack-years who had used tobacco
within the last 15 years were considered eligible. In total, 256 participants
underwent LDCT November 2016 through March 2017. The American College of
Radiology Lung Imaging Reporting and Data System (Lung-RADS) was used to
categorize the LDCT findings. Results: In total, 57%, 35.5%, 3.9%, and 3.5%
participants belonged to Lung-RADS categories 1, 2, 3, and 4, respectively.
Accordingly, 7.4% participants exhibited positive findings (category 3 or 4).
Lung cancer was diagnosed in one participant (stage IA, small cell lung cancer).
Other LDCT findings included pulmonary emphysema (32.8%), coronary artery
calcification (30.9%), old pulmonary tuberculosis (11.7%), bronchiectasis
(12.9%), interstitial lung disease with a usual interstitial pneumonia pattern
(1.2%), and pleural effusion (0.8%). Conclusion: Even though the size of our
study population was small, the positive rate of 7.4% was like or lower than
those in other lung cancer screening studies. Early lung cancer was detected
using LDCT screening in one participant. Lung-RADS may be applicable to
participants in Korea, where pulmonary tuberculosis is endemic.
PMID- 29962888
TI - Comparison of Filtered Back Projection, Hybrid Iterative Reconstruction, Model
Based Iterative Reconstruction, and Virtual Monoenergetic Reconstruction Images
at Both Low- and Standard-Dose Settings in Measurement of Emphysema Volume and
Airway Wall Thickness: A CT Phantom Study.
AB - Objective: To evaluate the accuracy of emphysema volume (EV) and airway
measurements (AMs) produced by various iterative reconstruction (IR) algorithms
and virtual monoenergetic images (VME) at both low- and standard-dose settings.
Materials and Methods: Computed tomography (CT) images were obtained on phantom
at both low- (30 mAs at 120 kVp) and standard-doses (100 mAs at 120 kVp). Each CT
scan was reconstructed using filtered back projection, hybrid IR (iDose4; Philips
Healthcare), model-based IR (IMR-R1, IMR-ST1, IMR-SP1; Philips Healthcare), and
VME at 70 keV (VME70). The EV of each air column and wall area percentage (WA%)
of each airway tube were measured in all algorithms. Absolute percentage
measurement errors of EV (APEvol) and AM (APEWA%) were then calculated. Results:
Emphysema volume was most accurately measured in IMR-R1 (APEvol in low-dose,
0.053 +/- 0.002; APEvol in standard-dose, 0.047 +/- 0.003; all p < 0.001) and AM
was the most accurate in IMR-SP1 on both low- and standard-doses CT (APEWA% in
low-dose, 0.067 +/- 0.002; APEWA% in standard-dose, 0.06 +/- 0.003; all p <
0.001). There were no significant differences in the APEvol of IMR-R1 between low
and standard-doses (all p > 0.05). VME70 showed a significantly higher APEvol
than iDose4, IMR-R1, and IMR-ST1 (all p < 0.004). VME70 also showed a
significantly higher APEWA% compared with the other algorithms (all p < 0.001).
Conclusion: IMR was the most accurate technique for measurement of both EV and
airway wall thickness. However, VME70 did not show a significantly better
accuracy compared with other algorithms.
PMID- 29962889
TI - PhytoKeys at 100: progress in sustainability, innovation, and speed to enhance
publication in plant systematics.
PMID- 29962890
TI - A taxonomic revision of Curarea Barneby & Krukoff (Menispermaceae).
AB - A monograph of Curarea, a neotropical genus in the plant family Menispermaceae,
is presented. Curarea is distinguished from related genera by the combination of
staminate flowers with sepals in two whorls and pistillate flowers with three
petals, three carpels and usually elongated carpophores bearing three sessile
drupelets. Nine species are recognised, amongst them two new to science, C.
gentryana from Ecuador and C. barnebyana, from Ecuador and Peru. Additionally,
two new combinations, C. iquitana and C. tomentocarpa, are proposed for distinct
taxa recovered in a multivariate analysis of quantitative characters of the
broadly distributed and morphologically variable C. toxicofera. The anatomy and
morphology of species in the genus is documented, identification key, species
descriptions, distribution maps and a preliminary conservation assessment for all
accepted species are also provided. Of the nine species recognised here, C.
barnebyana is assigned a preliminary status of Vulnerable, C. crassa (known only
from the coastal Atlantic Forest in Brazil) and C. gentryana (endemic to western
Ecuador) are both assigned a preliminary status of Endangered.
PMID- 29962891
TI - Taxonomic review of Ceratozamia (Zamiaceae) in the Sierra Madre Oriental, Mexico.
AB - The genus Ceratozamia is revised for the Sierra Madre Oriental in Mexico. This
region is one of the biogeographic areas with the greatest diversity of species
in this genus. These species are highly variable morphologically and this
variability has led to a complex taxonomic history with many synonyms,
particularly with reference to C. mexicana. We present a comprehensive taxonomic
revision with history of nomenclature and the morphology, relationships,
distribution and use of these species. We also introduce a key for their
identification, descriptions, full synonymy, nomenclatural notes, etymologies and
neotypes as well as taxonomic comments describing relevant taxonomic changes. We
recognise fourteen species in this biogeographic province: C. brevifrons, C.
chamberlainii, C. decumbens, C. delucana, C. fuscoviridis, C. hildae, C.
kuesteriana, C. latifolia, C. mexicana, C. morettii, C. sabatoi, C. tenuis, C.
totonacorum and C. zaragozae. This study provides a foundation for future
taxonomic work in Neotropical species of Ceratozamia.
PMID- 29962892
TI - New insights into the taxonomy of tribe Euclidieae (Brassicaceae), evidence from
nrITS sequence data.
AB - As currently delimitated, the species-rich mustard tribe Euclidieae DC.
(Brassicaceae) comprises 28 genera and 152 species distributed primarily in Asia.
To date, no tribe-wide comprehensive phylogenetic analysis has been conducted. In
this study, sequence data from the nuclear ribosomal internal transcribed spacer
(nrITS) region of 82 species in all 28 genera of Euclidieae were used to test its
monophyly and infer inter- and intra-generic relationships within. Phylogenetic
analyses revealed that Rhammatophyllum and Sisymbriopsis are embedded within
Solms-laubachia s.l., and Solms-laubachia lanuginosa (Eurycarpus lanuginosus)
fell outside the tribe. Therefore, Solms-laubachia s.l. as currently recognized
is not monophyletic and its generic delimitation needed further study. Besides,
our results suggest that the genera Lepidostemon, Neotorularia, and Tetracme are
polyphyletic.
PMID- 29962893
TI - Poa laegaardiana, a new species from Ecuador (Poaceae, Pooideae, Poeae, Poinae).
AB - Poa laegaardianasp. nov., is described and illustrated. The new species was found
growing on sandy, volcanic soil in Festuca-Calamagrostis dominated grasslands
southwest of Ambato and 2.2 km from Fecundo Vela in Provincia de Bolivar. The new
species is morphologically similar to Poa gigantea but differs in having glumes
3/4 to 7/8 as long as the adjacent lemmas, a callus with a sparse, short, dorsal
tuft of woolly hairs, culms 50-72 cm tall and spikelets 4.1-4.8 mm long. In
addition, we include a key to the narrow-spikelike panicled species of Poa in
Ecuador.
PMID- 29962894
TI - Sindora stipitata (Detarioideae, Leguminosae), a new species from Thailand.
AB - Sindora stipitata, a new species in the subfamily Detarioideae (Leguminosae),
collected from Nakhon Phanom Province, Thailand, is described and illustrated.
The new species is morphologically similar to S. leiocarpa but differs in its
smaller stature (3-5 m high), 6-foliolate paripinnate leaves, falcate persistent
stipules, presence of a petal auricle, absence of a petal claw, stipitate ovary
and capitate stigma. A key to the Thailand and Malesia species of Sindora is
provided.
PMID- 29962896
TI - Mechanics of amorphous solids-identification and constitutive modelling.
PMID- 29962895
TI - The Environmental Benefits Mapping and Analysis Program - Community Edition
(BenMAP-CE): A tool to estimate the health and economic benefits of reducing air
pollution.
AB - A number of software tools exist to estimate the health and economic impacts
associated with air quality changes. Over the past 15 years, the U.S.
Environmental Protection Agency and its partners invested substantial time and
resources in developing the Environmental Benefits Mapping and Analysis Program -
Community Edition (BenMAP-CE). BenMAP-CE is a publicly available, PC-based open
source software program that can be configured to conduct health impact
assessments to inform air quality policies anywhere in the world. The developers
coded the platform in C# and made the source code available in GitHub, with the
goal of building a collaborative relationship with programmers with expertise in
other environmental modeling programs. The team recently improved the BenMAP-CE
user experience and incorporated new features, while also building a cadre of
analysts and BenMAP-CE training instructors in Latin America and Southeast Asia.
PMID- 29962897
TI - Application of activated barrier hopping theory to viscoplastic modeling of
glassy polymers.
AB - An established statistical mechanical theory of amorphous polymer deformation has
been incorporated as a plastic mechanism into a constitutive model and applied to
a range of polymer mechanical deformations. The temperature and rate dependence
of the tensile yield of PVC, as reported in early studies, has been modeled to
high levels of accuracy. Tensile experiments on PET reported here are analyzed
similarly and good accuracy is also achieved. The frequently observed increase in
the gradient of the plot of yield stress against logarithm of strain rate is an
inherent feature of the constitutive model. The form of temperature dependence of
the yield that is predicted by the model is found to give an accurate
representation. The constitutive model is developed in two-dimensional form and
implemented as a user-defined subroutine in the finite element package ABAQUS.
This analysis is applied to the tensile experiments on PET, in some of which
strain is localized in the form of shear bands and necks. These deformations are
modeled with partial success, though adiabatic heating of the instability causes
inaccuracies for this isothermal implementation of the model. The plastic
mechanism has advantages over the Eyring process, is equally tractable, and
presents no particular difficulties in implementation with finite elements.
PMID- 29962898
TI - A computational study of crimping and expansion of bioresorbable polymeric
stents.
AB - This paper studied the mechanical performance of four bioresorbable PLLA stents,
i.e., Absorb, Elixir, Igaki-Tamai and RevaMedical, during crimping and expansion
using the finite element method. Abaqus CAE was used to create the geometrical
models for the four stents. A tri-folded balloon was created using NX software.
For the stents, elastic-plastic behaviour was used, with hardening implemented by
considering the increase of yield stress with the plastic strain. The tri-folded
balloon was treated as linear elastic. To simulate the crimping of stents, a set
of 12 rigid plates were generated around the stents with a radially enforced
displacement. During crimping, the stents were compressed from a diameter of 3 mm
to 1.2 mm, with the maximum stress developed at both inner and outer sides of the
U-bends. During expansion, the stent inner diameter increased to 3 mm at the peak
pressure and then recoiled to different final diameters after balloon deflation
due to different stent designs. The maximum stress was found again at the U-bends
of stents. Diameter change, recoiling effect and radial strength/stiffness were
also compared for the four stents to assess the effect of design variation on
stent performance. The effect of loading rate on stent deformation was also
simulated by considering the time-dependent plastic behaviour of polymeric
material.
PMID- 29962899
TI - Multivalent Mannose-Decorated NIR Nanoprobes for Targeting Pan Lymph Nodes.
AB - Lymphadenectomy is a prerequisite for most malignancies to define the precise
staging of cancer, as well as resect the possible metastases completely. While it
improves prognosis, lymphadenectomy often causes postoperative edema or bleeding
because of unclear surgical margins. In this study, we synthesized near-infrared
(NIR) fluorescent nanoprobes with conjugating various mannose moieties on the
surface to target macrophages in the lymph node. Armed with these NIR nanoprobes,
we demonstrated the feasibility of intraoperative pan lymph nodes (PLN) mapping
and real-time optical imaging under the NIR fluorescence imaging system. We found
that even single mannose-conjugated ZW800-1 showed specific uptake in lymph nodes
within 4 h, and multiple mannose-employed polyrotaxanes highlighted PLN
efficiently with low background signals in major organs. This technology can help
surgeons perform lymphadenectomy with ease and safety by identifying all regional
lymph nodes proficiently after a single intravenous injection of NIR nanoprobes.
PMID- 29962901
TI - Continuous dry dispersion of multi-walled carbon nanotubes to aerosols with high
concentrations of individual fibers.
AB - The assessment of the toxicity of airborne nanofibers is an important task. It
relies on toxicological inhalation studies and validated exposure measurement
techniques. Both require nanofiber-containing aerosols of known morphological
composition and controlled fraction of individual fibers. Here, a dry powder
dispersion method is presented that operates with mixtures of nanofibers and
microscale beads. Aerosolization experiments of mixtures of multi-walled carbon
nanotubes (MWCNTs) and glass beads that were continuously fed into a Venturi
nozzle enabled high generation rates of aerosols composed of individual and
agglomerate nanofiber structures. The aerosol process achieved good stability
over more than 2 h with respect to concentration and aerodynamic size
distribution. Its operation duration is limited only by the reservoir volume of
the cyclone used to separate the beads from the aerosol. The aerosol
concentration can be controlled by changing the mass ratio of MWCNTs and glass
beads or by adapting the mass feed rate to the nozzle. For two agglomerated MWCNT
materials, aerosol concentrations ranged from 1700 to 64,000 nano-objects per
cm3. Comprehensive scanning electron microscope analysis of filter samples was
performed to categorize and determine the morphological composition of the
aerosol, its fiber content as well as fiber length and diameter distributions.
High fractions of individual fibers of up to 34% were obtained, which shows the
setup to be capable of dispersing also highly tangled MWCNT agglomerates
effectively.
PMID- 29962900
TI - Infrared Multiple Photon Dissociation Spectroscopy of Cationized Canavanine: Side
Chain Substitution Influences Gas-Phase Zwitterion Formation?.
AB - Infrared multiple photon dissociation spectroscopy was performed on protonated
and cationized canavanine (Cav), a non-protein amino acid oxy-analog of arginine.
Infrared spectra in the XH stretching region (3000 - 4000 cm-1) were obtained at
the Centre Laser Infrarouge d'Orsay (CLIO) facility. Comparison of the
experimental infrared spectra with scaled harmonic frequencies at the B3LYP/6
31+G(d,p) level of theory indicates that canavanine is in a canonical neutral
form in CavH+, CavLi+, and CavNa+; therefore, these cations are charge-solvated
structures. The infrared spectrum of CavK+ is consistent with a mixture of Cav in
canonical and zwitterionic forms leading to both charge-solvated and salt-bridged
cationic structures. The Cav moiety in CavCs+ is shown to be zwitterionic,
forming a salt-bridged structure for the cation. Infrared spectra in the
fingerprint region (1000 - 2000 cm-1) obtained at the FELIX Laboratory in
Nijmegen, Netherlands support these assignments. These results show that that a
single oxygen atom substitution in the side chain reduces the stability of the
zwitterion compared to that of the protein amino acid arginine (Arg), which has
been shown previously to adopt a zwitterionic structure in ArgNa+ and ArgK+. This
difference can be explained in part due to the decreased basicity of Cav (PA =
1001 kJ/mol) as compared to arginine (PA = 1051 kJ/mol), but not entirely, as
lysine, which has nearly the same proton affinity as Cav, (~993 kJ/mol) forms
only canonical structures with Na+, K+, and Cs+. A major difference between the
zwitterionic forms of ArgM+ and CavM+ is that the protonation site is on the side
chain for Arg and on the N-terminus for Cav. This results in systematically
weaker salt bridges in the Cav zwitterions. In addition, the presence of another
hydrogen-bonding acceptor atom in the side chain contributes to the stability of
the canonical structures for the smaller alkali cations.
PMID- 29962902
TI - Inferring social structure from continuous-time interaction data.
AB - Relational event data, which consist of events involving pairs of actors over
time, are now commonly available at the finest of temporal resolutions. Existing
continuous-time methods for modeling such data are based on point processes and
directly model interaction "contagion," whereby one interaction increases the
propensity of future interactions among actors, often as dictated by some latent
variable structure. In this article, we present an alternative approach to using
temporal-relational point process models for continuous-time event data. We
characterize interactions between a pair of actors as either spurious or as
resulting from an underlying, persistent connection in a latent social network.
We argue that consistent deviations from expected behavior, rather than solely
high frequency counts, are crucial for identifying well-established underlying
social relationships. This study aims to explore these latent network structures
in two contexts: one comprising of college students and another involving barn
swallows.
PMID- 29962903
TI - Optimizing Crystal Size of Photosystem II by Macroseeding: Toward Neutron Protein
Crystallography.
AB - Photosystem II (PSII) catalyzes the photo-oxidation of water to molecular oxygen
and protons. The water splitting reaction occurs inside the oxygen-evolving
complex (OEC) via a Mn4CaO5 cluster. To elucidate the reaction mechanism,
detailed structural information for each intermediate state of the OEC is
required. Despite the current high-resolution crystal structure of PSII at 1.85 A
and other efforts to follow the structural changes of the Mn4CaO5 cluster using X
ray free electron laser (XFEL) crystallography in addition to spectroscopic
methods, many details about the reaction mechanism and conformational changes in
the catalytic site during water oxidation still remain elusive. In this study, we
present a rarely found successful application of the conventional macroseeding
method to a large membrane protein like the dimeric PSII core complex (dPSIIcc).
Combining microseeding with macroseeding crystallization techniques allowed us to
reproducibly grow large dPSIIcc crystals with a size of ~3 mm. These large
crystals will help improve the data collected from spectroscopic methods like
polarized extended X-ray absorption fine structure (EXAFS) and single crystal
electron paramagnetic resonance (EPR) techniques and are a prerequisite for
determining a three-dimensional structure using neutron diffraction.
PMID- 29962905
TI - Looking inside ourselves: a culture of kindness.
AB - Looking inside ourselves-being present and attentive to our own and others' words
and feelings-helps us communicate and interact with a mindful, open heart.
Mindfulness and patient-centeredness help caregivers provide higher quality care.
Historical background on a predecessor of mindfulness-the biopsychosocial model
of health and disease, developed at the University of Rochester-provides context
for the mindfulness "movement" in health care. A culture of mindfulness,
supported by mindfulness and meditation training for physicians and other health
care providers, helps practitioners show greater compassion, kindness, and
humanity, all qualities that patients need and deserve. In the health care world,
many organizations have been created that focus on aspects of mindfulness. Some
have a more clinical emphasis and others focus on behavioral or neuroscience
research as it relates to meditation, mindfulness, compassion, and kindness.
Mindfulness is also being taught in business schools and corporations. Leaders
who approach their teams with respect, integrity, honesty, and kindness are more
effective leaders. Organizations like Google, Nike, and Aetna, among others, use
the concept of mindfulness, as well as emotional and social intelligence, to
build interpersonal competencies and create more people-centered workplaces. As
medical libraries live in the health care environment and medical library leaders
are key to libraries' present and future, there are strong reasons to address the
concepts of mindfulness and kindness and put them to work in the medical library
workplaces. A mindfulness meditation exercise closes the lecture, sending the
attendees out into their day with calm and open minds and hearts.
PMID- 29962906
TI - Learning while doing: program evaluation of the Medical Library Association
Systematic Review Project.
AB - Objectives: The Medical Library Association (MLA) Systematic Review Project aims
to conduct systematic reviews to identify the state of knowledge and research
gaps for fifteen top-ranked questions in the profession. In 2013, fifteen
volunteer-driven teams were recruited to conduct the systematic reviews. The
authors investigated the experiences of participants in this large-scale,
volunteer-driven approach to answering priority research questions and fostering
professional growth among health sciences librarians. Methods: A program
evaluation was conducted by inviting MLA Systematic Review Project team members
to complete an eleven-item online survey. Multiple-choice and short-answer
questions elicited experiences about outputs, successes and challenges, lessons
learned, and future directions. Participants were recruited by email, and
responses were collected over a two-week period beginning at the end of January
2016. Results: Eighty (8 team leaders, 72 team members) of 198 potential
respondents completed the survey. Eighty-four percent of respondents indicated
that the MLA Systematic Review Project should be repeated in the future and were
interested in participating in another systematic review. Team outputs included
journal articles, conference presentations or posters, and sharing via social
media. Thematic analysis of the short-answer questions yielded five broad themes:
learning and experience, interpersonal (networking), teamwork, outcomes, and
barriers. Discussion: A large-scale, volunteer-driven approach to performing
systematic reviews shows promise as a model for answering key questions in the
profession and demonstrates the value of experiential learning for acquiring
synthesis review skills and knowledge. Our project evaluation provides
recommendations to optimize this approach.
PMID- 29962907
TI - Defining data librarianship: a survey of competencies, skills, and training.
AB - Objectives: Many librarians are taking on new roles in research data services.
However, the emerging field of data librarianship, including specific roles and
competencies, has not been clearly established. This study aims to better define
data librarianship by exploring the skills and knowledge that data librarians
utilize and the training that they need to succeed. Methods: Librarians who do
data-related work were surveyed about their work and educational backgrounds and
asked to rate the relevance of a set of data-related skills and knowledge to
their work. Results: Respondents considered a broad range of skills and knowledge
important to their work, especially "soft skills" and personal characteristics,
like communication skills and the ability to develop relationships with
researchers. Traditional library skills like cataloging and collection
development were considered less important. A cluster analysis of the responses
revealed two types of data librarians: data generalists, who tend to provide data
services across a variety of fields, and subject specialists, who tend to provide
more specialized services to a distinct discipline. Discussion: The findings of
this study suggest that data librarians provide a broad range of services to
their users and, therefore, need a variety of skills and expertise. Libraries
hiring a data librarian may wish to consider whether their communities will be
best served by a data generalist or a subject specialist and write their job
postings accordingly. These findings also have implications for library schools,
which could consider adjusting their curricula to better prepare their students
for data librarian roles.
PMID- 29962904
TI - GLUCOCORTICOID EXCESS IN BONE AND MUSCLE.
AB - Glucocorticoids (GC), produced and released by the adrenal glands, regulate
numerous physiological processes in a wide range of tissues. Because of their
profound immunosuppressive and anti-inflammatory actions, GC are extensively used
for the treatment of immune and inflammatory conditions, the management of organ
transplantation, and as a component of chemotherapy regimens for cancers.
However, both pathologic endogenous elevation and long-term use of exogenous GC
are associated with severe adverse effects. In particular, excess GC has
devastating effects on the musculoskeletal system. GC increase bone resorption
and decrease formation leading to bone loss, microarchitectural deterioration and
fracture. GC also induce loss of muscle mass and strength leading to an increased
incidence of falls. The combined effects on bone and muscle account for the
increased fracture risk with GC. This review summarizes the advance in knowledge
in the last two decades about the mechanisms of action of GC in bone and muscle
and the attempts to interfere with the damaging actions of GC in these tissues
with the goal of developing more effective therapeutic strategies.
PMID- 29962908
TI - Essential and core books for veterinary medicine.
AB - Objectives: This study defined core and essential lists of recent, English
language veterinary medicine books using a data-driven methodology for potential
use by a broad audience, including libraries that are building collections
supporting veterinary sciences and One Health initiatives. Methods: Book titles
were collected from monograph citation databases, veterinary examination reading
lists, veterinary college textbook and library reserve lists, and published
bibliographies. These lists were combined into a single list with titles ranked
by the number of occurrences. Results: The methodology produced a core list of
122 monographs and an essential list of 33 titles. All titles are recent, edition
neutral, English language monographs. One title is out of print. Conclusions: The
methodology captured qualitative and quantitative input from four distinct
populations who use veterinary monographs: veterinary practitioners, educators,
researchers, and librarians. Data were collected and compiled to determine core
and essential lists that represented all groups. Unfortunately, data are not
available for all subareas of veterinary medicine, resulting in uneven subject
coverage. This methodology can be replicated and adapted for other subject areas.
PMID- 29962909
TI - Librarians collaborating to teach evidence-based practice: exploring partnerships
with professional organizations.
AB - Objective: The study sought to determine if librarians are collaborating with
nurses and professional nursing organizations to teach evidence-based practice
(EBP) continuing education courses, workshop, classes, or other training
activities. Methods: A 15-question survey was sent to 1,845 members of the
Medical Library Association through email. Results: The survey was completed by
201 consenting respondents. Some respondents (37) reported having experience
teaching continuing education in collaboration with professional health care
organizations and 8 respondents, more specifically, reported having experience
teaching EBP continuing education courses, workshops, classes, or other training
activities in collaboration with professional nursing organizations. Conclusions:
The survey results demonstrate that librarians are teaching continuing education
classes or workshops in collaboration with professional health care organizations
and reveal that there are a small number of librarians collaborating with
professional nursing organizations to teach EBP continuing education courses,
workshops, classes, or other training activities.
PMID- 29962910
TI - Use of annual surveying to identify technology trends and improve service
provision.
AB - Objective: At an academic health sciences library serving a wide variety of
disciplines, studying library users' technology use provides necessary
information on intersection points for library services. Administering a similar
survey annually for five years generated a holistic view of users' technology
needs and preferences over time. Methods: From 2012 to 2016, the University of
Florida Health Science Center Library (HSCL) annually administered a sixteen-to
twenty question survey addressing health sciences users' technology awareness and
use and their interest in using technology to engage with the library and its
services. The survey was distributed throughout the HSC via email invitation from
liaison librarians to their colleges and departments and advertisement on the
HSCL home page. Results: Smartphone ownership among survey respondents was nearly
universal, and a majority of respondents also owned a tablet. While respondents
were likely to check library hours, use medical apps, and use library electronic
resources from their mobile devices, they were unlikely to friend or follow the
library on Facebook or Twitter or send a call number from the catalog.
Respondents were more likely to have used EndNote than any other citation
management tool, but over 50% of respondents had never used each tool or never
heard of it. Conclusions: Annual review of survey results has allowed librarians
to identify users' needs and interests, leading to incremental changes in
services offered. Reviewing the aggregate data allowed strategic consideration of
how technology impacts library interactions with users, with implications toward
library marketing, training, and service development.
PMID- 29962911
TI - Accessibility of published research to practicing veterinarians.
AB - Objectives: This study established the percentage of veterinary research articles
that are freely available online, availability differences inside and outside of
core veterinary medicine publications, sources and trends in article availability
over time, and author archiving policies of veterinary journals. This research is
particularly important for unaffiliated practitioners who lack broad subscription
access and the librarians who assist them. Methods: Web of Science citation data
were collected for articles published from 2000-2014 by authors from twenty-eight
accredited US colleges of veterinary medicine. A sample of these articles was
searched by title in Google Scholar to determine which were freely available
online and their sources. Journals represented in this dataset and a basic list
of veterinary serials were cross-referenced with the Sherpa/RoMEO database to
determine author archiving policies and the percentage of articles that could
potentially be made freely available. Results: Over half (62%) of the sample
articles were freely available online, most of which (57%) were available from
publishers' websites. Articles published more recently were more likely to be
freely available. More articles were found to be available in 2017 (62%) than in
2015 (57%). Most (62%) of the included journals had policies allowing authors to
archive copies of their articles. Conclusions: Many articles are freely available
online, but opportunity exists to archive additional articles while complying
with existing copyright agreements. Articles in veterinary medicine-specific
journals are less likely to be freely available than those in interdisciplinary
journals. Requirements for federally funded research have likely influenced
article availability and may continue to do so.
PMID- 29962912
TI - Developing occupational therapy students' information and historical literacy
competencies: an interprofessional collaborative project.
AB - Objective: The study examined the efficacy of an interprofessional information
and historical literacy project implemented by an occupational therapy educator
and a librarian. Methods: A graduate course was revised to include information
and historical literacy objectives and instruction. A course-specific
questionnaire administered on the first and last day of class, assignment grades,
and course evaluations provided measures of project outcomes for six years.
Differences between questionnaire pre- and post-test means were determined using
t-tests. Course evaluation comments were analyzed to obtain qualitative
perceptions. Results: A significant difference (p<0.0001) was found between pre
test (M=3.93, SD=0.48) and post-test (M=4.67, SD=0.30) scores of total
information and historical literacy competence across all years (n=242).
Responses to individual items also differed significantly (p<0.0001). Student
ratings (n=189) from the course evaluation historical literacy objectives were
high (M=4.6 on a 5-point scale). Assignment quality and grades improved, and
course evaluation comments reflected student satisfaction. Conclusions: The
findings supported the hypothesis that students' self-reported information and
historical literacy competencies would increase after project participation.
Acquired skills were evident in students' assignments. Research to determine if
these capabilities were used post-graduation is needed. Because this was a course
specific project, findings are not generalizable; however, the instructional
methods developed for this project can serve as a model for effective
interprofessional collaboration. The broadening of information literacy
instruction to include discipline-specific historical literacy provides a unique
opportunity for health sciences librarians and educators. Developing students'
historical literacy in their chosen fields can help them understand their
profession's present status and be informed participants in shaping its future.
PMID- 29962913
TI - A comparison of the content and primary literature support for online medication
information provided by Lexicomp and Wikipedia.
AB - Objectives: The research compared the comprehensiveness and accuracy of two
online resources that provide drug information: Lexicomp and Wikipedia. Methods:
Medication information on five commonly prescribed medications was identified and
comparisons were made between resources and the relevant literature. An initial
content comparison of the following three categories of medication information
was performed: dose and instructions, uses, and adverse effects or warnings. The
content comparison included sixteen points of comparison for each of the five
investigated medications, totaling eighty content comparisons. For each of the
medications, adverse reactions that appeared in only one of the resources were
identified. When primary, peer-reviewed literature was not referenced supporting
the discrepant adverse reactions, a literature search was performed to determine
whether or not evidence existed to support the listed claims. Results: Lexicomp
consistently provided more medication information, with information provided in
95.0% (76/80) of the content, compared to Wikipedia's 42.5% (34/80). Lexicomp and
Wikipedia had information present in 91.4% (32/35) and 20.0% (7/35) of dosing and
instructions content, respectively. Adverse effects or warning content was
provided in 97.5% (39/40) of Lexicomp content and 55.0% (22/40) of Wikipedia
content. The "uses" category was present in both Lexicomp and Wikipedia for the 5
medications considered. Of adverse reactions listed solely in Lexicomp, 191/302
(63.2%) were supported by primary, peer-reviewed literature in contrast to 7/7
(100.0%) of adverse reactions listed only in Wikipedia. A review of US Food and
Drug Administration Prescribing Information and the Adverse Event Reporting
System dashboard found support for a respective 17/102 (16.7%) and 92/102 (90.2%)
of Lexicomp's adverse reactions that were not supported in the literature.
Conclusion: Lexicomp is a comprehensive medication information tool that contains
lists of adverse reactions that are not entirely supported by primary-peer
reviewed literature.
PMID- 29962914
TI - Promoting MedlinePlus utilization in a federally qualified health center using a
multimodal approach.
AB - Background: Most patients want more health information than their clinicians
provide during office visits. Written information can complement information that
is provided verbally, yet most primary care practices, including federally
qualified health centers, have not implemented systematic programs to ensure that
patients receive understandable, relevant, and accurate health information at the
point of care. MedlinePlus in particular is underutilized. Case Presentation: The
authors conducted a multimodal intervention to promote the use of MedlinePlus at
a federally qualified health center. We provided MedlinePlus training to
clinicians and patients through group and one-on-one trainings and multimedia
promotion. We administered pre- and post-intervention surveys to patients,
clinicians, and nurses to assess changes in the use and recognition of
MedlinePlus at the point of care. We used quantitative and qualitative data to
understand the impact of the intervention. A National Library of Medicine grant
provided resources that supported equipment and staff. Group training improved
use of MedlinePlus by clinicians and staff. One-on-one training was most
effective for patients, particularly when it was integrated into the work-flow.
Conclusions: A multimodal approach can promote use of MedlinePlus among community
health center patients. However, the process is labor- and resource-intensive and
requires careful attention to work flow and leveraging of brief opportunities.
PMID- 29962915
TI - Three professions come together for an interdisciplinary approach to 3D printing:
occupational therapy, biomedical engineering, and medical librarianship.
AB - Background: Although many libraries have offered 3D printing as a service or
available technology, there is a lack of information on course-integrated
programs for 3D printing in which the library played a primary role. Therefore,
librarians at the Touro College School of Health Sciences began exploring 3D
printing for inclusion in the occupational and physical therapy curriculum. Case
Presentation: The goal of this project was to educate occupational and physical
therapy students and faculty about the potential applications of 3D printing in
health care and provide hands-on experience, while increasing collaboration
between librarians and faculty. Students' tasks included designing and creating a
3D-printed assistive device as part of their course. Conclusion: Students were
able to successfully print assistive devices, demonstrating the feasibility of 3D
printing in a health sciences curriculum. Librarians involved with this project
reached approximately 78 students and 200 other librarians and faculty members.
3D printing at Touro College continues to evolve and expand; the trial 3D
printing course is being reviewed for formal adoption into the occupational
therapy curriculum, and additional funding for 3D printing technologies is
currently being allocated by Touro administration.
PMID- 29962916
TI - Leveraging accreditation to integrate sustainable information literacy
instruction into the medical school curriculum.
AB - Background: While the term "information literacy" is not often used, the skills
associated with that concept are now central to the mission and accreditation
process of medical schools. The simultaneous emphasis on critical thinking
skills, knowledge acquisition, active learning, and development and acceptance of
technology perfectly positions libraries to be central to and integrated into the
curriculum. Case Presentation: This case study discusses how one medical school
and health sciences library leveraged accreditation to develop a sustainable and
efficient flipped classroom model for teaching information literacy skills to
first-year medical students. The model provides first-year medical students with
the opportunity to learn information literacy skills, critical thinking skills,
and teamwork, and then practice these skills throughout the pre-clerkship years.
Conclusions: The curriculum was deemed a success and will be included in next
year's first-year curriculum. Faculty have reported substantial improvements in
the information sources that first-year medical students are using in subsequent
clinical reasoning conferences and in other parts of the curriculum. The
effectiveness of the curriculum model was assessed using a rubric.
PMID- 29962917
TI - Updating professional development for medical librarians to improve our evidence
based medicine and information literacy instruction.
AB - Medical librarians lack professional development opportunities in the critical
appraisal of biomedical evidence. An update to our professional development
opportunities could support our efforts to teach critical appraisal of biomedical
evidence during evidence-based medicine or information literacy instruction. If
we enhance our understanding of latent influences on evidence quality-such as
changes to Food and Drug Administration regulations, predatory or deceptive
publishing practices, and clinical trial study designs-we can improve our value
to medical education and hospital systems.
PMID- 29962918
TI - Reading graphic medicine at the National Library of Medicine.
AB - The Exhibition Program, part of the History of Medicine Division of the National
Library of Medicine, spotlights the collection of the library by creating
exhibitions and educational resources that explore the social and cultural
history of medicine. Our goal is to stimulate people's enthusiasm for history and
encourage visitors of all ages to learn more about themselves and their
communities. We do what we do because we believe that health and well-being are
fundamental human rights and are essential to our American way of life. And we
believe exhibitions are a logical expression of that commitment. Oftentimes,
exhibitions focus on underrepresented subjects or lesser-known types of
literature, which helps to inform the library's collection development activity.
Collection development staff take a keen interest in viewing exhibitions,
attending related lectures, and performing bibliographic research on topics that
are unlikely to be captured in conventional scientific and professional
literature. This heightened awareness leads staff to discover niche publishers,
significant authors, and unique titles, thereby enriching the collection for
future generations. Following the decision to embark on an exhibition about
graphic medicine, collections staff more closely investigated this class of
literature. This column explores how wider social and cultural influences can
change the medical literature and inform and enrich the collections policies of
an institution.
PMID- 29962919
TI - Supply-Doubled Pulse-Shaping High Voltage Pulser for CMUT Arrays.
AB - A supply-doubled pulse-shaping high voltage (HV) pulser is presented for medical
ultrasound imaging applications, particularly those that use capacitive
micromachined ultrasonic transducers (CMUT). The pulser employs a bootstrap
circuit combined with dynamically-biased stacked transistors, which allow HV
operation above process limit without lowering device reliability. The new pulser
overcomes supply voltage limitation of conventional unipolar pulsers by
generating output signals that are almost twice the supply level. It also can
generate three-level pulses to further optimize the transmit pressure signals. A
proof-of-concept prototype has been implemented in 0.18-MUm HV CMOS/DMOS
technology with 60 V devices. Measurement results show that the HV pulser can
safely generate controllable three-level pulses with up to 85 Vpp from 45 V
supply. Acoustic measurements are conducted connecting the pulser to a CMUT with
2 pF capacitance and 8.3 MHz center frequency. The pulse shape has been adjusted
for the CMUT under test to generate maximum pressure output and the results are
in good agreement with a large signal CMUT model.
PMID- 29962920
TI - Improving Blood Retinol Concentrations with Complementary Foods Fortified with
Moringa oleifera Leaf Powder - A Pilot Study.
AB - Vitamin A deficiency (VAD) remains a major public health issue and is reported to
be the cause of about 6 percent of child deaths under the age of 5 years in
Africa. Inadequate dietary intake of vitamin A-rich foods is a major cause of
VAD. Moringa oleifera leaf powder (MLP) is rich in nutrients particularly vitamin
A and its use in infant feeding has been explored. This pilot study was designed
to test the efficacy of MLP in improving blood retinol concentrations among
infants in a rural district in Ghana. A subset of infants participating in a
randomized controlled trial (ISRCTN14377902) were randomly assigned to receive
one of the three study foods (MCL-35g and MS-5g both of which were fortified with
MLP, and a third food, CF-35g, a cereal legume blend which served as the control
food) in a feeding intervention that lasted for 6 weeks. Primary outcome of the
pilot study was retinol levels measured in 5 ml of whole blood at baseline and
endline using the iCheckTM Fluoro device. A total of 103 infant-mother pairs were
recruited at baseline, of which 65 completed the study. All the infants in the
study were vitamin A deficient at both baseline and endline when compared to the
World Health Organization (WHO) threshold of 0.70umol/l. There was however a
marginal non-significant increase in blood vitamin A concentrations for all three
groups at endline, with higher numerical increases seen in the two Moringa
supplemented groups. VAD is a significant public health problem and MLP could be
an affordable and sustainable means of combatting the issue. The efficacy of MLP
in improving vitamin A status of infants however needs to be ascertained in well
designed trials involving larger numbers of infants and which will last for
longer periods. Such studies will also be beneficial in helping to establish the
long-term acceptability of complementary foods that incorporate MLP in the target
population.
PMID- 29962923
TI - The synthesis of water-soluble CDM-AM copolymer by irradiation and its
solubilization effect on hydrophobic drugs.
AB - The beta-cyclodextrin-acrylamide (CDM-AM) copolymer was prepared from acrylamide
and beta-CD maleate (CDM) using 60Co gamma-ray irradiation method. The optimized
preparation conditions for the CDM-AM copolymer are as follows: CDM:AM mass ratio
of 1:1; irradiation dose of 4 kGy; and using 20 mL of DMF water solution. The
yield rate of CDM-AM was 75% in grams using these synthetic conditions. The
effects of the CDM-AM copolymer on the solubility and fungicidal activity of
natamycin (NM) and carbendazim (MBC) were investigated. The stability constant of
NM.CDM-AM and MBC.CDM-AM complexes at 303 K were of 13,446.06 M-1 and 2595.3 M-1,
respectively. The complexes were characterized using phase solubility diagrams,
NMR spectra and FT-IR spectra. The analysis of the biological activities of these
two complexes indicated that they possessed enhancing fungicidal activities
compared to NM and MBC alone.
PMID- 29962922
TI - Effects of Alpha-hydroxy-isocaproic acid upon Body Composition in a Type I
Diabetic Patient with Muscle Atrophy - A Case Study.
AB - Research involving dietary supplement interventions for sarcopenia and osteopenia
in type 1 diabetes patients is scarce. Here we present a case study of a type 1
diabetic patient that was treated with supplemental alpha-hydroxy-isocaproic acid
(alpha-HICA) for 120 days. Several measures of body composition by dual x-ray
absorptiometry, blood markers, and maximum voluntary contraction parameters were
assessed at baseline and after 120 days. The patient's baseline weight was 73.2
kg, which increased to 75.2 kg by the 120-day assessment. Salient mass
distribution changes included increases of trunk fat mass (+0.4 kg), trunk fat
free mass (+0.2 kg), total trunk mass (+0.2 kg), and a decrease of 8 percent in
trunk fat mass contribution. Handgrip strength increased by 58.84 N, whereas
isometric force in the leg press decreased by 347.15 N. Amelioration of BMD Z
scores from -0.7 to 0.5 and T-scores from -1.0 to -0.9 were noted. Importantly,
full hematologic measures and weekly nutritional counselling assessments revealed
no signs of adverse effects with alpha-HICA supplementation. Due to the
imperative of maintaining FFM, strength and bone mass in these patients,
additional research is necessary to confirm these promising results and to
clarify whether leucine and/or one of its derivatives might be clinically useful.
PMID- 29962921
TI - Aryl Hydrocarbon Receptor Diet and Breast Cancer Risk.
AB - Breast cancer is the most common type of cancer and leading cause of cancer
mortality among women worldwide. However, the majority of breast malignancies are
of sporadic etiology. Therefore, identifying risk-mitigating factors may
significantly decrease the burden of breast cancer. Diet can have both a
predisposing and protective role in breast tumorigenesis. However, establishing
efficacy of dietary constituents for cancer prevention has been limited by
suboptimal dietary assessment. There is a need to acquire new experimental
evidence that can be used to discriminate beneficial from harmful dietary
constituents. The aryl hydrocarbon receptor (AhR) is a ligand-activated
transcription factor that is recognized as the mediator of halogenated and
polycyclic aromatic hydrocarbon toxicities. Importantly, evidence points to a
breast tumor-promoting role for the AhR. Preclinical and clinical studies suggest
that the AhR is overexpressed in advanced and triple negative breast cancers.
Several dietary constituents, namely flavonoid compounds, have demonstrated
inhibitory effects on AhR activation. Given this background, in this paper we
elaborate on the working hypothesis that a diet rich in AhR food agonists favors
breast tumor development, whereas a diet rich in AhR food antagonists is
protective. As an initial approach to developing an AhR diet hypothesis, we
conducted a review of published studies reporting on the association between
intake of AhR inhibitory foods and risk of breast cancer. To assist the reader
with interpretation of the concepts leading to the AhR diet hypothesis, we have
preceded this review with an overview of AhR biology and its role in breast
cancer development.
PMID- 29962924
TI - Prevalence of BRAFV600E Mutation in Follicular Variant of Papillary Thyroid
Carcinoma and Non-Invasive Follicular Tumor with Papillary-Like Nuclear Features
(NIFTP) in a BRAFV600E Prevalent Area.
AB - Background: BRAFV600E mutation status and prevalence of non-invasive follicular
thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been
reported in Korea. The aim of this study was to investigate the significance of
the BRAFV600E mutation in the follicular variant of papillary thyroid carcinoma
(FVPTC) and to determine the prevalence of NIFTP in BRAFV600E mutation-prevalent
Korean patients. Methods: This study retrospectively analyzed 1,417 consecutive
patients who underwent total thyroidectomy with routine prophylactic central
lymph node dissection for papillary thyroid carcinoma (PTC). BRAFV600E mutation
analysis was performed routinely using multiplex polymerase chain reaction by
applying dual priming oligonucleotide. Clinicopathological characteristics and
ultrasonographic findings were compared between BRAFV600E mutation-positive and
negative groups for FVPTC. Pathologists reviewed the pathology slides according
to consensus diagnostic criteria for the encapsulated FVPTC and NIFTP. Results:
The prevalence of the BRAFV600E mutation in all subtypes of PTC was 61.0%
(861/1,411). FVPTC presented a BRAFV600E mutation rate of 27.3%. The FVPTC
patients with BRAFV600E mutation were older than those with no BRAFV600E mutation
(P = 0.021). The prevalence of NIFTP was 0.18% among all PTC patients (2/1,411)
and the proportion of NIFTP among FVPTC was 9.1% (2/22). Conclusion: The
BRAFV600E mutation is prevalent in Korean patients with FVPTC in a region with
high frequency of the BRAFV600E mutation and very low prevalence of NIFTP
compared with that reported in western studies.
PMID- 29962925
TI - Medical Litigations Associated with Cataract Surgery in Korea.
AB - Background: To analyze the results of court rulings about medical litigations
related to cataract surgery in Korea. Methods: We collected 50 anonymized
judgements regarding cataract surgery between 2000 and 2016 and analyzed the
reasons for the medical litigations, the court rulings, the reasons for
compensation, and the amount claimed and finally awarded. Results: Forty-eight
litigations (96%) resulted from errors in treatment, and the reasons were as
follows: endophthalmitis, dissatisfaction of visual outcome or ocular discomfort,
bullous keratopathy or corneal opacity, retinal detachment, glaucoma or vitreous
hemorrhage due to the progression of an underlying diabetic retinopathy, and
others in order. Two litigations (4%) arose due to errors in diagnosis. Among the
50 final cases, 21 litigations (42%) were decided in favor of the plaintiff, and
29 litigations (58%) were decided against the plaintiff and dismissed. Ten cases
awarded damages to the plaintiffs because of a violation of duty of care, and 11
cases awarded damages due to a violation of informed consent. When comparing
cases with errors in diagnosis to cases with errors in treatment, there was no
significant difference in the relative risk of a defendant's verdict (P = 0.503).
The total amount of awarded damages was KRW 439,124,496 (USD 399,204), and the
average amount was KRW 20,910,690 (USD 19,010). Conclusion: Nearly half of the
cases were decided in favor of the plaintiff due to the violation of informed
consent. This study's results will be helpful in understanding the results of
medical litigations regarding cataract surgery and reducing future lawsuits.
PMID- 29962927
TI - North Korean Medical Journals in the Galapagos.
PMID- 29962926
TI - Influence of CYP2D6 Polymorphism on the Pharmacokinetic/Pharmacodynamic
Characteristics of Carvedilol in Healthy Korean Volunteers.
AB - Background: Carvedilol is commonly used to treat hypertension as a beta- and
alpha1-adrenoreceptor blocker, but it is metabolized by CYP2D6, and CYP2D6*10
allele is dominant in Asian population. The objective of this study was to assess
the influence of CYP2D6 polymorphisms on the pharmacokinetic (PK) and
pharmacodynamic (PD) characteristics of carvedilol in healthy Korean volunteers.
Methods: A PK/PD study for a single and multiple dosing of carvedilol were
conducted. All volunteers in 3 genotypic groups received single oral dose of
carvedilol 12.5 mg for 3 days, then 25 mg QD for 5 days, and 12.5 mg QD for
another 3 days. PK parameters for carvedilol and its three metabolites were
determined using non-compartmental analysis. For PD properties, blood pressure,
heart rate, and the chronotropic dose 25 (CD25) value were obtained. Results: The
IM_2 group with two *10 alleles (intermediate metabolizers) exhibited lower
clearance of carvedilol as well as higher area under the curve (AUC) for O
desmethyl carvedilol. The ratio of CD25 to baseline at multiple dosing was
significantly higher in the combined IM group (IM_1 and IM_2) than in the EM
group, however, the ratio of CD25 after single and multiple dosing and the other
PD markers were not significantly different between the 3 genotypic groups
compared with the baseline. Conclusion: These findings showed that CYP2D6
genotype influenced the PK characteristics of carvedilol and no differences in PD
response were observed in Korean healthy volunteers. Registered at the
ClinicalTrials.gov, NCT02286934.
PMID- 29962928
TI - Using design strategies from microfluidic device patents to support idea
generation.
AB - Microfluidics has been an important method in providing answers to a wide variety
of research questions in chemistry, biochemistry, and biology. Microfluidic
designers benefit from instructional textbooks describing foundational principles
and practices in developing microfluidic devices; however, these texts do not
offer guidance about how to generate design concepts for microfluidic devices.
Research on design in related fields, such as mechanical engineering, documents
the difficulties engineers face when attempting to generate novel ideas. For
microfluidic device designers, support during idea generation may lead to greater
exploration of potential innovations in design. To investigate successful idea
generation in microfluidics, we analyzed successful microfluidic US patents,
selecting those with the key word "microfluidic" over a 2-year period. After
analyzing the features and functions of 235 patents, we identified 36 distinct
design strategies in microfluidic devices. We document each strategy, and
demonstrate their usefulness in a concept generation study of practitioners in
microfluidic design. While some of the identified design strategies may be
familiar to microfluidic designers, exposure to this large set of strategies
helped participants generate more diverse, creative, and unique microfluidic
design concepts, which are considered best practices in idea generation.
PMID- 29962929
TI - The Stability and Repeatability of Spontaneous Sympathetic Baroreflex Sensitivity
in Healthy Young Individuals.
AB - Spontaneous sympathetic baroreflex sensitivity (BRS) is a valuable tool for
assessing how well the baroreflex buffers beat-to-beat changes in blood pressure.
However, there has yet to be a study involving appropriate statistical tests to
examine the stability of sympathetic BRS within an experimental session and the
repeatability between separate sessions. The aim of this study was to use intra
class correlations, ordinary least products regression, and Bland-Altman analyses
to examine the stability and repeatability of spontaneous sympathetic BRS
assessment. In addition, the influence of recording duration on values of BRS was
assessed. In eighty-four healthy young individuals (49 males, 35 females),
continuous measurements of blood pressure, heart rate and muscle sympathetic
nerve activity (MSNA) were recorded for 10 min. In a subgroup of 13 participants
(11 male, 2 female) the measurements were repeated on a separate day. Sympathetic
BRS was quantified using MSNA burst incidence (BRSinc) and total MSNA (BRStotal)
for the first 5-min period, the second 5-min period, and a 2-min segment taken
from the second 5-min period. Intra-class correlation coefficients indicated
moderate stability in sympathetic BRSinc and BRStotal between the first and
second 5-min periods in males (BRSincr = 0.63, BRStotalr = 0.78) and females
(BRSincr = 0.61, BRStotalr = 0.47) with no proportional bias, but with fixed bias
for BRSinc in females. When comparing the first 5-min with the 2-min period (n =
76), the intra-class correlation coefficient indicated poor to moderate
repeatability in sympathetic BRSinc and BRStotal for males (BRSincr = -0.01,
BRStotalr = 0.70) and females (BRSincr = 0.46, BRStotalr = 0.39). However, Bland
Altman analysis revealed a fixed bias for BRStotal in males and proportional bias
for BRStotal in females, with lower BRS values for 5-min recordings. In the
subgroup, intra-class correlations indicated moderate repeatability for measures
of BRSinc (9 male, 2 female, r = 0.63) and BRStotal (6 male, 2 female, r = 0.68)
assessed using 5-min periods recorded on separate days. However, Bland-Altman
analysis indicated proportional bias for BRSinc and fixed bias for BRStotal. In
conclusion, measures of spontaneous sympathetic BRS are moderately stable and
repeatable within and between testing sessions in healthy young adults, provided
that the same length of recording is used when making comparisons.
PMID- 29962930
TI - Proton Transport Chains in Glucose Metabolism: Mind the Proton.
AB - The Embden-Meyerhof-Parnas (EMP) pathway comprises eleven cytosolic enzymes
interacting to metabolize glucose to lactic acid [CH3CH(OH)COOH]. Glycolysis is
largely considered as the conversion of glucose to pyruvate (CH3COCOO-). We
consider glycolysis to be a cellular process and as such, transporters mediating
glucose uptake and lactic acid release and enable the flow of metabolites through
the cell, must be considered as part of the EMP pathway. In this review, we
consider the flow of metabolites to be coupled to a flow of energy that is
irreversible and sufficient to form ordered structures. This latter principle is
highlighted by discussing that lactate dehydrogenase (LDH) complexes irreversibly
reduce pyruvate/H+ to lactate [CH3CH(OH)COO-], or irreversibly catalyze the
opposite reaction, oxidation of lactate to pyruvate/H+. However, both LDH
complexes are considered to be driven by postulated proton transport chains.
Metabolism of glucose to two lactic acids is introduced as a unidirectional,
continuously flowing pathway. In an organism, cell membrane-located proton-linked
monocarboxylate transporters catalyze the final step of glycolysis, the release
of lactic acid. Consequently, both pyruvate and lactate are discussed as
intermediate products of glycolysis and substrates of regulated crosscuts of the
glycolytic flow.
PMID- 29962931
TI - Big Data Analysis of Genes Associated With Neuropsychiatric Disorders in an
Alzheimer's Disease Animal Model.
AB - Alzheimer's disease is a neurodegenerative disease characterized by the
impairment of cognitive function and loss of memory, affecting millions of
individuals worldwide. With the dramatic increase in the prevalence of
Alzheimer's disease, it is expected to impose extensive public health and
economic burden. However, this burden is particularly heavy on the caregivers of
Alzheimer's disease patients eliciting neuropsychiatric symptoms that include
mood swings, hallucinations, and depression. Interestingly, these
neuropsychiatric symptoms are shared across symptoms of bipolar disorder,
schizophrenia, and major depression disorder. Despite the similarities in
symptomatology, comorbidities of Alzheimer's disease and these neuropsychiatric
disorders have not been studied in the Alzheimer's disease model. Here, we
explore the comprehensive changes in gene expression of genes that are associated
with bipolar disorder, schizophrenia, and major depression disorder through the
microarray of an Alzheimer's disease animal model, the forebrain specific PSEN
double knockout mouse. To analyze the genes related with these three
neuropsychiatric disorders within the scope of our microarray data, we used
selected 1207 of a total of 45,037 genes that satisfied our selection criteria.
These genes were selected on the basis of 14 Gene Ontology terms significantly
relevant with the three disorders which were identified by previous research
conducted by the Psychiatric Genomics Consortium. Our study revealed that the
forebrain specific deletion of Alzheimer's disease genes can significantly alter
neuropsychiatric disorder associated genes. Most importantly, most of these
significantly altered genes were found to be involved with schizophrenia. Taken
together, we suggest that the synaptic dysfunction by mutation of Alzheimer's
disease genes can lead to the manifestation of not only memory loss and
impairments in cognition, but also neuropsychiatric symptoms.
PMID- 29962932
TI - Enhancing the Ecological Validity of fMRI Memory Research Using Virtual Reality.
AB - Functional magnetic resonance imaging (fMRI) is a powerful research tool to
understand the neural underpinnings of human memory. However, as memory is known
to be context-dependent, differences in contexts between naturalistic settings
and the MRI scanner environment may potentially confound neuroimaging findings.
Virtual reality (VR) provides a unique opportunity to mitigate this issue by
allowing memories to be formed and/or retrieved within immersive, navigable,
visuospatial contexts. This can enhance the ecological validity of task
paradigms, while still ensuring that researchers maintain experimental control
over critical aspects of the learning and testing experience. This mini-review
surveys the growing body of fMRI studies that have incorporated VR to address
critical questions about human memory. These studies have adopted a variety of
approaches, including presenting research participants with VR experiences in the
scanner, asking participants to retrieve information that they had previously
acquired in a VR environment, or identifying neural correlates of behavioral
metrics obtained through VR-based tasks performed outside the scanner. Although
most such studies to date have focused on spatial or navigational memory, we also
discuss the promise of VR in aiding other areas of memory research and
facilitating research into clinical disorders.
PMID- 29962933
TI - Wnts Promote Synaptic Assembly Through T-Cell Specific Transcription Factors in
Caenorhabditis elegans.
AB - Synapses are specialized neuronal connections essential for neuronal function.
Defects in synaptic assembly or maintenance usually lead to various neurological
disorders. Synaptic assembly is regulated by secreted molecules such as Wnts.
Wnts are a large family of conserved glycosylated signaling molecules involved in
many aspects of neural development and maintenance. However, the molecular
mechanisms by which Wnts regulate synaptic assembly remain elusive due to the
large number of ligands/receptors, the diversity of signaling cascades and the
complexity of the nervous system. In this study, through genetic manipulation, we
uncover that C. elegans Wnt-2 (CWN-2) is required for synaptic development. The
CWN-2 signal is required during both embryonic and postembryonic development, in
the nervous system and intestine, for promoting synaptic assembly. Furthermore,
we provide genetic evidence for CWN-2 promoting synaptogenesis through the
Frizzled receptor (FZD) CFZ-2, the Dishevelled (DVL) DSH-2, the beta-catenin SYS
1 and the only T-cell specific transcription factor POP-1/TCF. Importantly, it is
the first time to report the requirement of a TCF for presynaptic assembly. These
findings expand our understanding of the synaptogenic mechanisms and may provide
therapeutic insights into Wnt-related neurological disorders.
PMID- 29962934
TI - Endophilin A and B Join Forces With Clathrin to Mediate Synaptic Vesicle
Recycling in Caenorhabditis elegans.
AB - Synaptic vesicle (SV) recycling enables ongoing transmitter release, even during
prolonged activity. SV membrane and proteins are retrieved by ultrafast
endocytosis and new SVs are formed from synaptic endosomes (large vesicles-LVs).
Many proteins contribute to SV recycling, e.g., endophilin, synaptojanin, dynamin
and clathrin, while the site of action of these proteins (at the plasma membrane
(PM) vs. at the endosomal membrane) is only partially understood. Here, we
investigated the roles of endophilin A (UNC-57), endophilin-related protein (ERP
1, homologous to human endophilin B1) and of clathrin, in SV recycling at the
cholinergic neuromuscular junction (NMJ) of C. elegans. erp-1 mutants exhibited
reduced transmission and a progressive reduction in optogenetically evoked muscle
contraction, indicative of impaired SV recycling. This was confirmed by
electrophysiology, where particularly endophilin A (UNC-57), but also endophilin
B (ERP-1) mutants exhibited reduced transmission. By optogenetic and
electrophysiological analysis, phenotypes in the unc-57; erp-1 double mutant are
largely dominated by the unc-57 mutation, arguing for partially redundant
functions of endophilins A and B, but also hinting at a back-up mechanism for
neuronal endocytosis. By electron microscopy (EM), we observed that unc-57 and
erp-1; unc-57 double mutants showed increased numbers of synaptic endosomes of
large size, assigning a role for both proteins at the endosome, because endosomal
disintegration into new SVs, but not formation of endosomes were hampered.
Accordingly, only low amounts of SVs were present. Also erp-1 mutants show
reduced SV numbers (but no increase in LVs), thus ERP-1 contributes to SV
formation. We analyzed temperature-sensitive mutants of clathrin heavy chain (chc
1), as well as erp-1; chc-1 and unc-57; chc-1 double mutants. SV recycling
phenotypes were obvious from optogenetic stimulation experiments. By EM, chc-1
mutants showed formation of numerous and large endosomes, arguing that clathrin,
as shown for mammalian synapses, acts at the endosome in formation of new SVs.
Without endophilins, clathrin formed endosomes at the PM, while endophilins A and
B compensated for the loss of clathrin at the PM, under conditions of high SV
turnover.
PMID- 29962935
TI - Chromatin Remodeling Proteins in Epilepsy: Lessons From CHD2-Associated Epilepsy.
AB - The chromodomain helicase DNA-binding (CHD) family of proteins are ATP-dependent
chromatin remodelers that contribute to the reorganization of chromatin structure
and deposition of histone variants necessary to regulate gene expression. CHD
proteins play an important role in neurodevelopment, as pathogenic variants in
CHD1, CHD2, CHD4, CHD7 and CHD8 have been associated with a range of neurological
phenotypes, including autism spectrum disorder (ASD), intellectual disability
(ID) and epilepsy. Pathogenic variants in CHD2 are associated with developmental
epileptic encephalopathy (DEE) in humans, however little is known about how these
variants contribute to this disorder. Of the nine CHD family members, CHD2 is the
only one that leads to a brain-restricted phenotype when disrupted in humans.
This suggests that despite being expressed ubiquitously, CHD2 has a unique role
in human brain development and function. In this review, we will discuss the
phenotypic spectrum of patients with pathogenic variants in CHD2, current animal
models of CHD2 deficiency, and the role of CHD2 in proliferation, neurogenesis,
neuronal differentiation, chromatin remodeling and DNA-repair. We also consider
how CHD2 depletion can affect each of these biological mechanisms and how these
defects may underpin neurodevelopmental disorders including epilepsy.
PMID- 29962937
TI - Loss of Axon Bifurcation in Mesencephalic Trigeminal Neurons Impairs the Maximal
Biting Force in Npr2-Deficient Mice.
AB - Bifurcation of axons from dorsal root ganglion (DRG) and cranial sensory ganglion
(CSG) neurons is mediated by a cGMP-dependent signaling pathway composed of the
ligand C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2 and
the cGMP-dependent protein kinase I (cGKI). Here, we demonstrate that
mesencephalic trigeminal neurons (MTN) which are the only somatosensory neurons
whose cell bodies are located within the CNS co-express Npr2 and cGKI. Afferents
of MTNs form Y-shaped branches in rhombomere 2 where the ligand CNP is expressed.
Analyzing mouse mutants deficient for CNP or Npr2 we found that in the absence of
CNP-induced cGMP signaling MTN afferents no longer bifurcate and instead extend
either into the trigeminal root or caudally in the hindbrain. Since MTNs provide
sensory information from jaw closing muscles and periodontal ligaments we
measured the bite force of conditional mouse mutants of Npr2
(Npr2flox/flox;Engr1Cre ) that lack bifurcation of MTN whereas the bifurcation of
trigeminal afferents is normal. Our study revealed that the maximal biting force
of both sexes is reduced in Npr2flox/flox;Engr1Cre mice as compared to their
Npr2flox/flox littermate controls. In conclusion sensory feedback mechanisms from
jaw closing muscles or periodontal ligaments might be impaired in the absence of
MTN axon bifurcation.
PMID- 29962936
TI - Specificity, Versatility, and Continual Development: The Power of Optogenetics
for Epilepsy Research.
AB - Optogenetics is a powerful and rapidly expanding set of techniques that use
genetically encoded light sensitive proteins such as opsins. Through the
selective expression of these exogenous light-sensitive proteins, researchers
gain the ability to modulate neuronal activity, intracellular signaling pathways,
or gene expression with spatial, directional, temporal, and cell-type
specificity. Optogenetics provides a versatile toolbox and has significantly
advanced a variety of neuroscience fields. In this review, using recent epilepsy
research as a focal point, we highlight how the specificity, versatility, and
continual development of new optogenetic related tools advances our understanding
of neuronal circuits and neurological disorders. We additionally provide a brief
overview of some currently available optogenetic tools including for the
selective expression of opsins.
PMID- 29962939
TI - Microfluidics of Small-Population Neurons Allows for a Precise Quantification of
the Peripheral Axonal Growth State.
AB - Neurons are morphologically the most complex cell types and are characterized by
a significant degree of axonal autonomy as well as having efficient means of
communication between axons and neuronal cell bodies. For studying the response
to axonal injury, compartmentalized microfluidic chambers (MFCs) have become the
method of choice because they allow for the selective treatment of axons,
independently of the soma, in a highly controllable and reproducible manner. A
major disadvantage of these devices is the relatively large number of neurons
needed for seeding, which makes them impractical to use with small-population
neurons, such as sensory neurons of the mouse. Here, we describe a simple
approach of seeding and culturing neurons in MFCs that allows for a dramatic
reduction of neurons required to 10,000 neurons per device. This technique
facilitates efficient experiments with small-population neurons in
compartmentalized MFCs. We used this experimental setup to determine the
intrinsic axonal growth state of adult mouse sensory neurons derived from dorsal
root ganglia (DRG) and even trigeminal ganglia (TG). In combination with a newly
developed linear Sholl analysis tool, we have examined the axonal growth
responses of DRG and TG neurons to various cocktails of neurotrophins, glial cell
line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and
leptin. Precise quantification of axonal outgrowth revealed specific differences
in the potency of each combination to promote axonal regeneration and to switch
neurons into an intrinsic axonal growth state. This novel experimental setup
opens the way to practicable microfluidic analyses of neurons that have
previously been largely neglected simply due to insufficient numbers, including
sensory neurons, sympathetic neurons and motor neurons.
PMID- 29962940
TI - The Glycolytic Metabolite, Fructose-1,6-bisphosphate, Blocks Epileptiform Bursts
by Attenuating Voltage-Activated Calcium Currents in Hippocampal Slices.
AB - Manipulation of metabolic pathways (e.g., ketogenic diet (KD), glycolytic
inhibition) alters neural excitability and represents a novel strategy for
treatment of drug-refractory seizures. We have previously shown that inhibition
of glycolysis suppresses epileptiform activity in hippocampal slices. In the
present study, we aimed to examine the role of a "branching" metabolic pathway
stemming off glycolysis (i.e., the pentose-phosphate pathway, PPP) in regulating
seizure activity, by using a potent PPP stimulator and glycolytic intermediate,
fructose-1,6-bisphosphate (F1,6BP). Employing electrophysiological approaches, we
investigated the action of F1,6BP on epileptiform population bursts, intrinsic
neuronal firing, glutamatergic and GABAergic synaptic transmission and voltage
activated calcium currents (ICa) in the CA3 area of hippocampal slices. Bath
application of F1,6BP (2.5-5 mM) blocked epileptiform population bursts induced
in Mg2+-free medium containing 4-aminopyridine, in ~2/3 of the slices. The
blockade occurred relatively rapidly (~4 min), suggesting an extracellular
mechanism. However, F1,6BP did not block spontaneous intrinsic firing of the CA3
neurons (when synaptic transmission was eliminated with DNQX, AP-5 and SR95531),
nor did it significantly reduce AMPA or NMDA receptor-mediated excitatory
postsynaptic currents (EPSCAMPA and EPSCNMDA). In contrast, F1,6BP caused
moderate reduction (~50%) in GABAA receptor-mediated current, suggesting it
affects excitatory and inhibitory synapses differently. Finally and unexpectedly,
F1,6BP consistently attenuated ICa by ~40% without altering channel activation or
inactivation kinetics, which may explain its anticonvulsant action, at least in
this in vitro seizure model. Consistent with these results, epileptiform
population bursts in CA3 were readily blocked by the nonspecific Ca2+ channel
blocker, CdCl2 (20 MUM), suggesting that these bursts are calcium dependent.
Altogether, these data demonstrate that the glycolytic metabolite, F1,6BP, blocks
epileptiform activity via a previously unrecognized extracellular effect on ICa,
which provides new insight into the metabolic control of neural excitability.
PMID- 29962938
TI - The Role of the Microtubule Cytoskeleton in Neurodevelopmental Disorders.
AB - Neurons depend on the highly dynamic microtubule (MT) cytoskeleton for many
different processes during early embryonic development including cell division
and migration, intracellular trafficking and signal transduction, as well as
proper axon guidance and synapse formation. The coordination and support from MTs
is crucial for newly formed neurons to migrate appropriately in order to
establish neural connections. Once connections are made, MTs provide structural
integrity and support to maintain neural connectivity throughout development.
Abnormalities in neural migration and connectivity due to genetic mutations of MT
associated proteins can lead to detrimental developmental defects. Growing
evidence suggests that these mutations are associated with many different
neurodevelopmental disorders, including intellectual disabilities (ID) and autism
spectrum disorders (ASD). In this review article, we highlight the crucial role
of the MT cytoskeleton in the context of neurodevelopment and summarize genetic
mutations of various MT related proteins that may underlie or contribute to
neurodevelopmental disorders.
PMID- 29962941
TI - Prefrontal Neuronal Excitability Maintains Cocaine-Associated Memory During
Retrieval.
AB - Presentation of drug-associated cues provokes craving and drug seeking, and
elimination of these associative memories would facilitate recovery from
addiction. Emotionally salient memories are maintained during retrieval, as
particular pharmacologic or optogenetic perturbations of memory circuits during
retrieval, but not after, can induce long-lasting memory impairments. For
example, in rats, inhibition of noradrenergic beta-receptors, which control
intrinsic neuronal excitability, in the prelimbic medial prefrontal cortex (PL
mPFC) can cause long-term memory impairments that prevent subsequent cocaine
induced reinstatement. The physiologic mechanisms that allow noradrenergic
signaling to maintain drug-associated memories during retrieval, however, are
unclear. Here we combine patch-clamp electrophysiology ex vivo and behavioral
neuropharmacology in vivo to evaluate the mechanisms that maintain drug
associated memory during retrieval in rats. Consistent with previous studies, we
find that cocaine experience increases the intrinsic excitability of pyramidal
neurons in PL-mPFC. In addition, we now find that this intrinsic plasticity
positively predicts the retrieval of a cocaine-induced conditioned place
preference (CPP) memory, suggesting that such plasticity may contribute to drug
associated memory retrieval. In further support of this, we find that
pharmacological blockade of a cAMP-dependent signaling cascade, which allows
noradrenergic signaling to elevate neuronal excitability, is required for memory
maintenance during retrieval. Thus, inhibition of PL-mPFC neuronal excitability
during memory retrieval not only leads to long-term deficits in the memory, but
this memory deficit provides protection against subsequent cocaine-induced
reinstatement. These data reveal that PL-mPFC intrinsic neuronal excitability
maintains a cocaine-associated memory during retrieval and suggest a unique
mechanism whereby drug-associated memories could be targeted for elimination.
PMID- 29962942
TI - Multimodal Communication in Aphasia: Perception and Production of Co-speech
Gestures During Face-to-Face Conversation.
AB - The role of nonverbal communication in patients with post-stroke language
impairment (aphasia) is not yet fully understood. This study investigated how
aphasic patients perceive and produce co-speech gestures during face-to-face
interaction, and whether distinct brain lesions would predict the frequency of
spontaneous co-speech gesturing. For this purpose, we recorded samples of
conversations in patients with aphasia and healthy participants. Gesture
perception was assessed by means of a head-mounted eye-tracking system, and the
produced co-speech gestures were coded according to a linguistic classification
system. The main results are that meaning-laden gestures (e.g., iconic gestures
representing object shapes) are more likely to attract visual attention than
meaningless hand movements, and that patients with aphasia are more likely to
fixate co-speech gestures overall than healthy participants. This implies that
patients with aphasia may benefit from the multimodal information provided by co
speech gestures. On the level of co-speech gesture production, we found that
patients with damage to the anterior part of the arcuate fasciculus showed a
higher frequency of meaning-laden gestures. This area lies in close vicinity to
the premotor cortex and is considered to be important for speech production. This
may suggest that the use of meaning-laden gestures depends on the integrity of
patients' speech production abilities.
PMID- 29962943
TI - Event-Based, Timescale Invariant Unsupervised Online Deep Learning With STDP.
AB - Learning of hierarchical features with spiking neurons has mostly been
investigated in the database framework of standard deep learning systems.
However, the properties of neuromorphic systems could be particularly interesting
for learning from continuous sensor data in real-world settings. In this work, we
introduce a deep spiking convolutional neural network of integrate-and-fire (IF)
neurons which performs unsupervised online deep learning with spike-timing
dependent plasticity (STDP) from a stream of asynchronous and continuous event
based data. In contrast to previous approaches to unsupervised deep learning with
spikes, where layers were trained successively, we introduce a mechanism to train
all layers of the network simultaneously. This allows approximate online
inference already during the learning process and makes our architecture suitable
for online learning and inference. We show that it is possible to train the
network without providing implicit information about the database, such as the
number of classes and the duration of stimuli presentation. By designing an STDP
learning rule which depends only on relative spike timings, we make our network
fully event-driven and able to operate without defining an absolute timescale of
its dynamics. Our architecture requires only a small number of generic mechanisms
and therefore enforces few constraints on a possible neuromorphic hardware
implementation. These characteristics make our network one of the few
neuromorphic architecture which could directly learn features and perform
inference from an event-based vision sensor.
PMID- 29962944
TI - Unraveling the Complexity of Amyotrophic Lateral Sclerosis Survival Prediction.
AB - Objective: The heterogeneity of amyotrophic lateral sclerosis (ALS) survival
duration, which varies from <1 year to >10 years, challenges clinical decisions
and trials. Utilizing data from 801 deceased ALS patients, we: (1) assess the
underlying complex relationships among common clinical ALS metrics; (2) identify
which clinical ALS metrics are the "best" survival predictors and how their
predictive ability changes as a function of disease progression. Methods:
Analyses included examination of relationships within the raw data as well as the
construction of interactive survival regression and classification models
(generalized linear model and random forests model). Dimensionality reduction and
feature clustering enabled decomposition of clinical variable contributions.
Thirty-eight metrics were utilized, including Medical Research Council (MRC)
muscle scores; respiratory function, including forced vital capacity (FVC) and
FVC % predicted, oxygen saturation, negative inspiratory force (NIF); the Revised
ALS Functional Rating Scale (ALSFRS-R) and its activities of daily living (ADL)
and respiratory sub-scores; body weight; onset type, onset age, gender, and
height. Prognostic random forest models confirm the dominance of patient age
related parameters decline in classifying survival at thresholds of 30, 60, 90,
and 180 days and 1, 2, 3, 4, and 5 years. Results: Collective prognostic insight
derived from the overall investigation includes: multi-dimensionality of ALSFRS-R
scores suggests cautious usage for survival forecasting; upper and lower
extremities independently degenerate and are autonomous from respiratory decline,
with the latter associating with nearer-to-death classifications; height and
weight-based metrics are auxiliary predictors for farther-from-death
classifications; sex and onset site (limb, bulbar) are not independent survival
predictors due to age co-correlation. Conclusion: The dimensionality and
fluctuating predictors of ALS survival must be considered when developing
predictive models for clinical trial development or in-clinic usage. Additional
independent metrics and possible revisions to current metrics, like the ALSFRS-R,
are needed to capture the underlying complexity needed for population and
personalized forecasting of survival.
PMID- 29962945
TI - Cortical Proprioceptive Processing Is Altered by Aging.
AB - Proprioceptive perception is impaired with aging, but little is known about aging
related deterioration of proprioception at the cortical level. Corticokinematic
coherence (CKC) between limb kinematic and magnetoencephalographic (MEG) signals
reflects cortical processing of proprioceptive afference. We, thus, compared CKC
strength to ankle movements between younger and older subjects, and examined
whether CKC predicts postural stability. Fifteen younger (range 18-31 years) and
eight older (66-73 years) sedentary volunteers were seated in MEG, while their
right and left ankle joints were moved separately at 2 Hz (for 4 min each) using
a novel MEG-compatible ankle-movement actuator. Coherence was computed between
foot acceleration and MEG signals. CKC strength at the movement frequency (F0)
and its first harmonic (F1) was quantified. In addition, postural sway was
quantified during standing eyes-open and eyes-closed tasks to estimate motor
performance. CKC peaked in the gradiometers over the vertex, and was
significantly stronger (~76%) at F0 for the older than younger subjects. At F1,
only the dominant-leg CKC was significantly stronger (~15%) for the older than
younger subjects. In addition, CKC (at F1) was significantly stronger in the non
dominant than dominant leg, but only in the younger subjects. Postural sway was
significantly (~64%) higher in the older than younger subjects when standing with
eyes closed. Regression models indicated that CKC strength at F1 in the dominant
leg and age were the only significant predictors for postural sway. Our results
indicated that aging-related cortical-proprioceptive processing is altered by
aging. Stronger CKC may reflect poorer cortical proprioceptive processing, and
not solely the amount of proprioceptive afference as suggested earlier. In
combination with ankle-movement actuator, CKC can be efficiently used to unravel
proprioception-related-neuronal mechanisms and the related plastic changes in
aging, rehabilitation, motor-skill acquisition, motor disorders etc.
PMID- 29962946
TI - APOE and Alzheimer's Disease: Neuroimaging of Metabolic and Cerebrovascular
Dysfunction.
AB - Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset
Alzheimer's Disease (AD), and is associated with impairments in cerebral
metabolism and cerebrovascular function. A substantial body of literature now
points to E4 as a driver of multiple impairments seen in AD, including blunted
brain insulin signaling, mismanagement of brain cholesterol and fatty acids,
reductions in blood brain barrier (BBB) integrity, and decreased cerebral glucose
uptake. Various neuroimaging techniques, in particular positron emission
topography (PET) and magnetic resonance imaging (MRI), have been instrumental in
characterizing these metabolic and vascular deficits associated with this
important AD risk factor. In the current mini-review article, we summarize the
known effects of APOE on cerebral metabolism and cerebrovascular function, with a
special emphasis on recent findings via neuroimaging approaches.
PMID- 29962947
TI - Scutellarin Enhances Antitumor Effects and Attenuates the Toxicity of Bleomycin
in H22 Ascites Tumor-Bearing Mice.
AB - Bleomycin (BLM) is a broad spectrum anti-tumor drug and inducing pulmonary
fibrosis. As an anti-tumor drug without immunosuppression, it is urgent to find a
drug that reduces the side effects of BLM. Scutellarin (SCU), a flavone extracted
from Erigeron breviscapus (Vant.) Hand-Mazz, has anti-inflammatory activity and
ability to inhibit tumor cell growth, migration, and invasion. However, the
combined role of SCU and BLM treatment in tumor is unclear. This study aimed to
investigate the possible effect and related mechanisms of BLM combined with SCU
in the treatment of tumor through in vivo and in vitro experiments. In vivo
experiments showed that BLM combined with SCU in the treatment of mice bearing
H22 ascites tumor prolonged the survival time, alleviated BLM-induced pulmonary
fibrosis, reduced the production of TNF-alpha; IL-6, and the levels of MDA and
MPO. BLM combined with SCU increased the apoptotic rate of H22 ascites cells and
the levels of cleaved-caspases-3 and -8. Furthermore, BLM combined with SCU
increased the protein expression of p53 and gene expression of miR-29b, and
decreased the expression of TGF-beta1. In vitro experiment results showed that
BLM combined with SCU inhibited the viability of H22 cells and MRC-5 cells,
promoted H22 cell apoptosis, up-regulated the protein expression of p53 and down
regulated the protein expression of alpha-SMA and collagen-I in MRC-5 cells.
These experimental results suggested that SCU could enhance the anti-tumor effect
of BLM and reduce BLM-induced pulmonary fibrosis, indicating SCU as a potential
adjuvant for BLM in the future.
PMID- 29962948
TI - Who Is Who in Adenosine Transport.
AB - Extracellular adenosine concentrations are regulated by a panel of membrane
transporters which, in most cases, mediate its uptake into cells. Adenosine
transporters belong to two gene families encoding Equilibrative and Concentrative
Nucleoside Transporter proteins (ENTs and CNTs, respectively). The lack of
appropriate pharmacological tools targeting every transporter subtype has
introduced some bias on the current knowledge of the role of these transporters
in modulating adenosine levels. In this regard, ENT1, for which pharmacology is
relatively well-developed, has often been identified as a major player in
purinergic signaling. Nevertheless, other transporters such as CNT2 and CNT3 can
also contribute to purinergic modulation based on their high affinity for
adenosine and concentrative capacity. Moreover, both transporter proteins have
also been shown to be under purinergic regulation via P1 receptors in different
cell types, which further supports its relevance in purinergic signaling. Thus,
several transporter proteins regulate extracellular adenosine levels. Moreover,
CNT and ENT proteins are differentially expressed in tissues but also in
particular cell types. Accordingly, transporter-mediated fine tuning of adenosine
levels is cell and tissue specific. Future developments focusing on CNT
pharmacology are needed to unveil transporter subtype-specific events.
PMID- 29962949
TI - trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like
Behaviors by Regulation of Brain-Gut Axis.
AB - Background: Irritable bowel syndrome (IBS) is a functional disorder characterized
by abdominal pain and abnormalities in defecation associated with psychiatric
disorders such as depression and anxiety due to the dysfunction of brain-gut
axis. This study aims to determine whether trans-Resveratrol affects chronic
acute combined stress (CACS)-induced IBS-like symptoms including depression,
anxiety and intestinal dysfunction. Methods: ICR male mice were exposed to the
CACS for 3 weeks. trans-Resveratrol were administrated daily (2.5, 5, and 10
mg/kg, i.g.) 30 min before CACS. Behavioral tests were performed to evaluate the
treatment effects of trans-Resveratrol on IBS. Hippocampus tissues were collected
and processed Golgi staining and immuno-blot analysis. Ileum and colon tissues
were collected and processed Hematoxylin and Eosin staining and immuno-blot
analysis. Results: Administration with trans-Resveratrol before CACS for 3 weeks
significantly reversed CACS-induced depression- and anxiety-like behaviors and
intestinal dysfunction in mice, which implied a crucial role of trans-Resveratrol
in treatment of IBS-like disorder. Furthermore, trans-Resveratrol improved
hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier
structure against CACS insults. The further study suggested that trans
Resveratrol normalized phosphodiesterases 4A (PDE4A) expression and CREB-BDNF
signaling that were disturbed by CACS. The increased pCREB and BDNF expression in
the hippocampus were found, while decreased pCREB and BDNF levels were observed
after treatment with trans-Resveratrol. Conclusions: The dual effects of trans
Resveratrol on stress-induced psychiatric and intestinal dysfunction may be
related to normalization of PDE4A expression and subsequent pCREB-BDNF signaling
in the hippocampus, ileum and colon.
PMID- 29962950
TI - UPLC-QTOF/MSE and Bioassay Are Available Approaches for Identifying Quality
Fluctuation of Xueshuantong Lyophilized Powder in Clinic.
AB - Xueshuantong Lyophilized Powder (XST), consisting of a series of saponins
extracted from Panax notoginseng, is widely applied to treat acute cerebral
infarction, stroke, and coronary heart disease in China. However, most adverse
drug reactions (ADR) in clinic are caused by quality problems of XST. In this
study, six batches of certainly abnormal, four batches of possibly abnormal XST,
and eight batches of normal XST were obtained from the clinical practice. Their
quality fluctuations were identified by ultra-performance liquid chromatography
coupled with an electrospray ionization quadrupole time-of-flight mass
spectrometry operating in MSE mode (UPLC-QTOF/MSE) and bioassays including
antithrombin and proplasmin assay. Fourteen potential components responsible for
clinical ADR were identified by UPLC-QTOF/MSE, especially ginsenoside Rg1, Rg3,
Rb1 and notoginsenoside R1. In addition, 83.3% (5/6) and 50.0% (3/6) certainly
abnormal samples could be identified by UPLC-QTOF/MSE and bioassay, respectively.
Interestingly, further integration of the two methods could entirely identify all
the certainly abnormal samples and inferred that all the possibly abnormal
samples were closely related to their quality fluctuation. It indicates that it
is advisable to combine UPLC-QTOF/MSE and bioassay for identifying quality
fluctuation of XST, and thus reduce its ADR in clinic.
PMID- 29962951
TI - Ginseng Compatibility Environment Attenuates Toxicity and Keeps Efficacy in Cor
Pulmonale Treated by Fuzi Beimu Incompatibility Through the Coordinated Crosstalk
of PKA and Epac Signaling Pathways.
AB - Cor pulmonale is characterized by severe right ventricular dysfunction caused by
lung disease, particularly chronic obstructive pulmonary disease, which can lead
to pulmonary hypertension. Our previous study has demonstrated that Fuzi and
Beimu compatibility (FBC), a traditional TCM compatibility taboo, improves lung
function in early-stage of pulmonary hypertension through the synergistic action
of beta-ARs signals. However, FBC increases cardiotoxicity with prolonged
treatment and disease progression. Considering that the compatibility environment
influences the exertion of the medicine, we selected ginseng for coordinating the
compatibility environment to improve the security and extend the therapeutic time
window of FBC. Monocrotaline-induced cor pulmonale rats were treated with FBC,
ginseng, or ginseng combined with FBC (G/FBC). Then, the pulmonary and cardiac
functions of the rats were examined to evaluate the toxicity and efficacy of the
treatments. The crosstalk between PKA and Epac pathways was also studied. Results
showed that G/FBC ameliorated lung function similar to or even better than FBC
treatment did. Furthermore, G/FBC treatment attenuated FBC-induced
cardiotoxicity, which significantly restored cardiac dysfunction and clearly
decreased myocardial enzymes and apoptosis. The betaAR-Gs-PKA/CaMKII pathway was
inhibited and the Epac1/ERK1/2 axis was activated in G/FBC group. These findings
indicate that ginseng compatibility environment could improve pulmonary function
and attenuate cardiotoxicity in cor pulmonale via the coordinated crosstalk of
PKA and Epac pathways, implying that ginseng could be used to prevent detrimental
cardiotoxicity in cor pulmonale treatment.
PMID- 29962952
TI - Protective Effects of Casticin From Vitex trifolia Alleviate Eosinophilic Airway
Inflammation and Oxidative Stress in a Murine Asthma Model.
AB - Casticin has been isolated from Vitex trifolia and found to have anti
inflammatory and anti-tumor properties. We also previously discovered that
casticin can reduce pro-inflammatory cytokines and ICAM-1 expression in
inflammatory pulmonary epithelial cells. In the present study, we evaluated
whether casticin reduced airway hyper-responsiveness (AHR), airway inflammation,
and oxidative stress in the lungs of a murine asthma model and alleviated
inflammatory and oxidative responses in tracheal epithelial cells. Female BALB/c
mice were randomly divided into five groups: normal controls, ovalbumin (OVA)
induced asthma, and OVA-induced asthma treated with intraperitoneal injection of
casticin (5 or 10 mg/kg) or prednisolone (5 mg/kg). Casticin reduced AHR, goblet
cell hyperplasia, and oxidative responses in the lungs of mice with asthma.
Mechanistic studies revealed that casticin attenuated the levels of Th2 cytokine
in bronchoalveolar lavage fluids and regulated the expression of Th2 cytokine and
chemokine genes in the lung. Casticin also significantly regulated oxidative
stress and reduced inflammation in the lungs of mice with asthma. Consequently,
inflammatory tracheal epithelial BEAS-2B cells treated with casticin had
significantly suppressed levels of pro-inflammatory cytokines and eotaxin, and
reduced THP-1 monocyte cell adherence to BEAS-2B cells via suppressed ICAM-1
expression. Thus, casticin is a powerful immunomodulator, ameliorating
pathological changes by suppressing Th2 cytokine expression in mice with asthma.
PMID- 29962953
TI - Sirt1 Activation by Post-ischemic Treatment With Lumbrokinase Protects Against
Myocardial Ischemia-Reperfusion Injury.
AB - Lumbrokinase is used as an oral supplement to support and maintain healthy
cardiovascular function, and to treat cardiovascular diseases in clinical for
more than 10 years. Up until now, the mechanism of the cardioprotective effects
of post-ischemic treatment with lumbrokinase has remained unclear. We therefore
investigated the signaling pathways involved in the amelioration of myocardial
ischemia-reperfusion (I-R) injury in rats treated with lumbrokinase 20 min after
myocardial ischemia. Compared to vehicle-treated rats, post-ischemic treatment
with lumbrokinase was associated with significant reductions in myocardial I-R
induced arrhythmias and myocardial damage, and an improvement in cardiac
function. Moreover, lumbrokinase significantly upregulated levels of silent
information regulator 1 (Sirt1). In addition, lumbrokinase significantly
increased manganese-dependent superoxide dismutase expression, decreased Cleaved
Caspase-3 expression, and induced deacetylation of FoxO1. On the other hand,
lumbrokinase also significantly downregulated levels of succinate dehydrogenase,
cytochrome c oxidase, nuclear factor kappa B (NF-kappaB) and elevated levels of
microtubule-associated protein light chain 3. Notably, the cardioprotective
effects of lumbrokinase were abolished by administration of the specific Sirt1
inhibitor EX527. These findings demonstrate that post-ischemic treatment with
lumbrokinase attenuates myocardial I-R injury through the activation of Sirt1
signaling, and thus enhances autophagic flux and reduces I-R-induced oxidative
damage, inflammation and apoptosis.
PMID- 29962954
TI - "Hard" Drug Repurposing for Precision Oncology: The Missing Link?
PMID- 29962955
TI - Panax ginseng Polysaccharide Protected H9c2 Cardiomyocyte From
Hypoxia/Reoxygenation Injury Through Regulating Mitochondrial Metabolism and RISK
Pathway.
AB - Background and Objective: Ischemic heart disease (IHD) has been the major issue
of public health. Panax ginseng (ginseng) has been verified as an effective
traditional Chinese medicines and exerted cardioprotective effect. This study
aimed to investigate the polysaccharide fraction of ginseng on
hypoxia/reoxygenation (H/R) injury in cardiomyocytes and the underlying
mechanisms. Methods: Ginseng was extracted by ethanol and fractionated by high
speed counter current chromatography (HSCCC) and column separation. The
cardioprotective effect was evaluated in H9c2 cardiomyocytes underwent H/R
treatment. The cell viability, apoptosis and mitochondrial respiration were
examined. Results: An acid polysaccharides fraction of ginseng (AP1) was
identified the most effective fraction in protecting cardiomyocytes from H/R
injury. AP1 restored the mitochondrial function by maintaining mitochondrial
membrane potential (MMP), blocking the release of cytochrome C, and increasing
the ATP generation and oxygen consumption rate (OCR) of cardiomyocytes.
Meanwhile, AP1 induced the expression of glucocorticoid receptor (GR) and
estrogen receptor (ER) which further activated reperfusion injury salvage kinase
(RISK) pathway. Finally, AP1 increased nitric oxide (NO) production and regulated
endothelial function by increasing endothelial NO synthase (eNOS) expression and
decreasing inducible NOS (iNOS) expression in H/R injury. Conclusion: The results
suggested that AP1 exerted a protective effect in myocardial H/R injury mainly
through maintaining myocardial mitochondrial function, thereby inhibiting
myocardial H/R caused apoptosis and increasing the expressions of GR and ER,
which in turn mediated the activation of RISK pathway and eNOS-dependent
mechanism to resist the reperfusion injury.
PMID- 29962957
TI - Deficiency of NOD1 Improves the beta-Adrenergic Modulation of Ca2+ Handling in a
Mouse Model of Heart Failure.
AB - Heart failure (HF) is a complex syndrome characterized by cardiac dysfunction,
Ca2+ mishandling, and chronic activation of the innate immune system. Reduced
cardiac output in HF leads to compensatory mechanisms via activation of the
adrenergic nervous system. In turn, chronic adrenergic overstimulation induces
pro-arrhythmic events, increasing the rate of sudden death in failing patients.
Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is an
innate immune modulator that plays a key role in HF progression. NOD1 deficiency
in mice prevents Ca2+ mishandling in HF under basal conditions, but its role
during beta-adrenergic stimulation remains unknown. Here, we evaluated whether
NOD1 regulates the beta-adrenergic modulation of Ca2+ signaling in HF. Ca2+
dynamics were examined before and after isoproterenol perfusion in cardiomyocytes
isolated from healthy and from post-myocardial infarction (PMI) wild-type (WT)
and Nod1-/- mice. Isoproterenol administration induced similar effects on
intracellular [Ca2+]i transients, cell contraction, and sarcoplasmic reticulum
(SR)-Ca2+ load in healthy WT and Nod1-/- cells. However, compared with WT-PMI
cells, isoproterenol exposure induced a significant increase in the [Ca2+]i
transients and cell contraction parameters in Nod1-/--PMI cells, which mainly due
to an increase in SR-Ca2+ load. NOD1 deficiency also prevented the increase in
diastolic Ca2+ leak (Ca2+ waves) induced by isoproterenol in PMI cells. mRNA
levels of beta1 and beta2 adrenergic receptors were significantly higher in Nod1
/--PMI hearts vs WT-PMI hearts. Healthy cardiomyocytes pre-treated with the
selective agonist of NOD1, iE-DAP, and perfused with isoproterenol showed
diminished [Ca2+]i transients amplitude, cell contraction, and SR-Ca2+ load
compared with vehicle-treated cells. iE-DAP-treated cells also presented
increased diastolic Ca2+ leak under beta-adrenergic stimulation. The selectivity
of iE-DAP on Ca2+ handling was validated by pre-treatment with the inactive
analog of NOD1, iE-Lys. Overall, our data establish that NOD1 deficiency improves
the beta-adrenergic modulation of Ca2+ handling in failing hearts.
PMID- 29962956
TI - The Current State of Cephalopod Science and Perspectives on the Most Critical
Challenges Ahead From Three Early-Career Researchers.
AB - Here, three researchers who have recently embarked on careers in cephalopod
biology discuss the current state of the field and offer their hopes for the
future. Seven major topics are explored: genetics, aquaculture, climate change,
welfare, behavior, cognition, and neurobiology. Recent developments in each of
these fields are reviewed and the potential of emerging technologies to address
specific gaps in knowledge about cephalopods are discussed. Throughout, the
authors highlight specific challenges that merit particular focus in the near
term. This review and prospectus is also intended to suggest some concrete near
term goals to cephalopod researchers and inspire those working outside the field
to consider the revelatory potential of these remarkable creatures.
PMID- 29962958
TI - Electron Density of Adipose Tissues Determined by Phase-Contrast Computed
Tomography Provides a Measure for Mitochondrial Density and Fat Content.
AB - Phase-contrast computed tomography (PCCT) is an X-ray-based imaging method
measuring differences in the refractive index during tissue passage. While
conventional X-ray techniques rely on the absorption of radiation due to
differing tissue-specific attenuation coefficients, PCCT enables the
determination of the electron density (ED). By the analysis of respective
phantoms and ex vivo specimens, we identified the components responsible for
different electron densities in murine adipose tissue depots to be cellular fat
and mitochondrial content, two parameters typically different between white
adipose tissue (WAT) and brown adipose tissue (BAT). Brown adipocytes provide
mammals with a means of non-shivering thermogenesis to defend normothermia in a
cold environment. Brown adipocytes are found in dedicated BAT depots and
interspersed within white fat depots, a cell type referred to as brite (brown in
white) adipocyte. Localization and quantification of brown and brite adipocytes
in situ allows an estimate of depot thermogenic capacity and potential
contribution to maximal metabolic rate in the cold. We utilized PCCT to infer the
composition of white, brite, and brown adipose tissue from ED of individual
depots. As proof of principle, we imaged mice 10, 20, and 30 days of age. During
this period, several WAT depots are known to undergo transient browning. Based on
ED, classical WAT and BAT could be clearly distinguished. Retroperitoneal and
inguinal WAT depots increased transiently in ED during the known remodeling from
white to brite/brown and back to white. We systematically analyzed 18
anatomically defined adipose tissue locations and identified changes in fat
content and mitochondrial density that imply an orchestrated pattern of
simultaneous browning and whitening on the organismic level. Taken together, PCCT
provides a three-dimensional imaging technique to visualize ED of tissues in
situ. Within the adipose organ, ED provides a measure of mitochondrial density
and fat content. Depending on experimental setting, these constitute surrogate
markers of cellular distribution of white, brite, and brown adipocytes and
thereby an estimate of thermogenic capacity.
PMID- 29962959
TI - Effects of Initial Performance, Gross Efficiency and O 2peak Characteristics on
Subsequent Adaptations to Endurance Training in Competitive Cyclists.
AB - The present study investigated the effects of initial levels of cycling
performance, peak oxygen uptake (O2peak) and gross efficiency (GE) on the
subsequent adaptations of these variables and their relationship following high
intensity training (HIT) designed to increase O2peak in competitive cyclists.
Sixty cyclists (O2peak = 61 +/- 6 mL kg-1 min-1) were assigned a 12-week training
program consisting of twenty-four supervised high-intensity interval training
sessions and ad libitum low intensity training. GE was calculated at 125, 175,
and 225 W and performance was determined by mean power during a 40-min time-trial
(Power40 min). In addition to correlation analyses between initial level and pre-
to post-intervention changes of the different variables, we compared these
changes between four groups where participants were categorized with either low
and/or high initial levels of O2peak and GE. Average volume of high- and low
intensity training during the 12-week intervention was 1.5 +/- 0.3 and 8.3 +/-
2.7 h.week-1, respectively. Following the 12-week training period, there was a
significant increase in absolute and body mass normalized O2peak and Power40 min
(p < 0.05) and a significant decrease in GE (p < 0.05) for all athletes pooled.
There was no change in body mass following the 12-week training period. We found
a moderate negative correlation between initial level of O2peak and the change in
O2peak following the training period (r = -0.32; p < 0.05). A small negative
correlation was also found between initial Power40 min and its change following
training both when expressed in absolute power and power normalized for body mass
(r = -0.27 and -0.28; both p < 0.05). A moderate negative correlation was also
found between initial levels for GE and its change following training (r = -0.44;
p < 0.01). There were no differences between the four groups based on initial
levels of O2peak and GE in the response to training on O2peak, GE, or Power40 min
(all p > 0.12). In conclusion, the present findings suggest that there are
statistically significant effects of initial levels of cycling performance and
O2peak and on the subsequent adaptations following a 12-week HIT program, but the
small and moderate effects indicate limited influence on training practice.
PMID- 29962960
TI - Sarcolipin Makes Heat, but Is It Adaptive Thermogenesis?
PMID- 29962962
TI - SQI Quality Evaluation Mechanism of Single-Lead ECG Signal Based on Simple
Heuristic Fusion and Fuzzy Comprehensive Evaluation.
AB - For both the acquisition of mobile electrocardiogram (ECG) devices and early
warning and diagnosis of clinical work, high-quality ECG signals is particularly
important. We describe an effective system which could be deployed as a stand
alone signal quality assessment algorithm for vetting the quality of ECG signals.
The proposed ECG quality assessment method is based on the simple heuristic
fusion and fuzzy comprehensive evaluation of the SQIs. This method includes two
modules, i.e., the quantification and extraction of Signal Quality Indexes (SQIs)
for different features, intelligent assessment and classification. First, simple
heuristic fusion is executed to extract SQIs and determine the following SQIs: R
peak detection match qSQI, QRS wave power spectrum distribution pSQI, kurtosis
kSQI, and baseline relative power basSQI. Then, combined with Cauchy
distribution, rectangular distribution and trapezoidal distribution, the
membership function of SQIs was quantified, and the fuzzy vector was established.
The bounded operator was selected for fuzzy synthesis, and the weighted
membership function was used to perform the assessment and classification. The
performance of the proposed method was tested on the database from Physionet ECG
database, with an accuracy (Acc) of 97.67%, sensitivity (Se) of 96.33% and
specificity (Sp) of 98.33% on the training set. Testing against the test datasets
resulted in scores of 94.67, 90.33, and 93.00%, respectively. There's no gold
standard exists for determining the quality of ECGs. However, the proposed
algorithm discriminates between high- and poor-quality ECGs, which could aid in
ECG acquisition for mobile ECG devices, early clinical diagnosis and early
warning.
PMID- 29962961
TI - Role of the Purkinje-Muscle Junction on the Ventricular Repolarization
Heterogeneity in the Healthy and Ischemic Ovine Ventricular Myocardium.
AB - Alteration of action potential duration (APD) heterogeneity contributes to
arrhythmogenesis. Purkinje-muscle junctions (PMJs) present differential
electrophysiological properties including longer APD. The goal of this study was
to determine if Purkinje-related or myocardial focal activation modulates
ventricular repolarization differentially in healthy and ischemic myocardium.
Simultaneous epicardial (EPI) and endocardial (ENDO) optical mapping was
performed on sheep left ventricular (LV) wedges with intact free-running Purkinje
network (N = 7). Preparations were paced on either ENDO or EPI surfaces, or the
free-running Purkinje fibers (PFs), mimicking normal activation. EPI and ENDO
APDs were assessed for each pacing configuration, before and after (7 min) of the
onset of no-flow ischemia. Experiments were supported by simulations. In control
conditions, maximal APD was found at endocardial PMJ sites. We observed a
significant transmural APD gradient for PF pacing with PMJ APD = 347 +/- 41 ms
and EPI APD = 273 +/- 36 ms (p < 0.001). A similar transmural gradient was
observed when pacing ENDO (49 +/- 31 ms; p = 0.005). However, the gradient was
reduced when pacing EPI (37 +/- 20 ms; p = 0.005). Global dispersion of
repolarization was the most pronounced for EPI pacing. In ischemia, both ENDO and
EPI APD were reduced (p = 0.005) and the transmural APD gradient (109 +/- 55 ms)
was increased when pacing ENDO compared to control condition or when pacing EPI
(p < 0.05). APD maxima remained localized at functional PMJs during ischemia.
Local repolarization dispersion was significantly higher at the PMJ than at other
sites. The results were consistent with simulations. We found that the activation
sequence modulates repolarization heterogeneity in the ischemic sheep LV. PMJs
remain active following ischemia and exert significant influence on local
repolarization patterns.
PMID- 29962963
TI - Responses of Intestinal Mucosal Barrier Functions of Rats to Simulated
Weightlessness.
AB - Exposure to microgravity or weightlessness leads to various adaptive and
pathophysiological alterations in digestive structures and physiology. The
current study was carried out to investigate responses of intestinal mucosal
barrier functions to simulated weightlessness, by using the hindlimb unloading
rats model. Compared with normal controls, simulated weightlessness damaged the
intestinal villi and structural integrity of tight junctions, up-regulated the
expression of pro-apoptotic protein Bax while down-regulated the expression of
anti-apoptotic protein Bcl-2, thus improved the intestinal permeability. It could
also influence intestinal microbiota composition with the expansion of
Bacteroidetes and decrease of Firmicutes. The predicted metagenomic analysis
emphasized significant dysbiosis associated differences in genes involved in
membrane transport, cofactors and vitamins metabolism, energy metabolism, and
genetic information processing. Moreover, simulated weightlessness could modify
the intestinal immune status characterized by the increase of proinflammatory
cytokines, decrease of secretory immunoglobulin A, and activation of
TLR4/MyD88/NF-kappaB signaling pathway in ileum. These results indicate the
simulated weightlessness disrupts intestinal mucosal barrier functions in animal
model. The data also emphasize the necessity of monitoring and regulating
astronauts' intestinal health during real space flights to prevent breakdowns in
intestinal homeostasis of crewmembers.
PMID- 29962964
TI - Syndecans and Enzymes Involved in Heparan Sulfate Biosynthesis and Degradation
Are Differentially Expressed During Human Odontogenesis.
AB - Syndecans belong to a four-member family of cell surface heparan sulfate
proteoglycans (HSPGs) abundantly present in various tissues. They are primarily
recognized as extracellular matrix (ECM) receptors able to bind various ECM
components and form gradients of morphogens and growth factors. Syndecans are
composed of core protein with distinctive cytoplasmic, transmembrane, and
extracellular domains to which several HS glycosaminoglycan (GAG) chains are
covalently attached. In development of composite organs, such as teeth,
expression patterns of syndecans display temporo-spatial shifts between
epithelial and mesenchymal tissue compartments. Along with diverse functional
properties of syndecans and generally large number of their interactors due to HS
GAG chain content, this suggests possible involvement of syndecans in modulation
of epithelial-to-mesenchymal crosstalk. Functional versatility of syndecans
greatly depends upon the biochemical properties of attached HS GAG chains. These
are specifically determined during the HS biosynthesis by the combinatorial
action of glycosyl-transferases (Exts/EXTs) and bi-functional sulfotransferases
(Ndsts/NDSTs), as well as by post-biosynthetic enzymatic cleavage of HS by the
only active endoglucuronidase in mammals, heparanase 1 (Hpse1/HPSE1). Matching
the essential requirement for HS during organogenesis, null-mutant animals for
genes encoding these enzymes display severe developmental anomalies of
mineralized tissues (including teeth) with embryonic or perinatal lethality. In
this study, we analyzed expression of syndecan HSPGs (syndecans 1, 2, and 4),
enzymes involved in HS biosynthesis (EXT1, NDST1, NDST2) and HS cleavage (HPSE1)
in human tooth germs during the early stages of odontogenesis. All of the
investigated factors displayed temporo-spatial differences in expression
patterns, and some of them showed distinctive asymmetries of expression domains.
Our findings suggest that these factors might be differentially involved in
cellular processes which take place during the early odontogenic sequence in
humans.
PMID- 29962965
TI - Inhibition of Prostate Smooth Muscle Contraction by Inhibitors of Polo-Like
Kinases.
AB - Background: Prostate smooth muscle contraction plays an important role for
pathophysiology and treatment of male lower urinary tract symptoms (LUTS) but is
incompletely understood. Because the efficacy of available medication is limited,
novel options and improved understanding of prostate smooth muscle contraction
are of high demand. Recently, a possible role of polo-like kinase 1 (PLK1) has
been suggested for smooth muscle contraction outside the lower urinary tract.
Here, we examined effects of PLK inhibitors on contraction of human prostate
tissue. Methods: Prostate tissues were obtained from radical prostatectomy. RT
PCR, Western blot and immunofluorescence were performed to detect PLK expression
and phosphorylated PLK. Smooth muscle contractions were induced by electric field
stimulation (EFS), alpha1-agonists, endothelin-1, or the thromboxane A2 analog
U46619 in organ bath. Results: RT-PCR, Western blot, and immunofluorescence
suggested expression of PLK1 in the human prostate, which may be located and
active in smooth muscle cells. EFS-induced contractions of prostate strips were
reduced by SBE 13 (1 MUM), cyclapolin 9 (3 MUM), TAK 960 (100 nM), and Ro 3280
(100 nM). SBE 13 and cyclapolin 9 inhibited contractions by the alpha1-agonists
methoxamine, phenylephrine, and noradrenaline. In contrast, no effects of SBE 13
or cyclapolin 9 on endothelin-1- or U46619-induced contractions were observed.
Conclusion: Alpha1-adrenergic smooth muscle contraction in the human prostate can
be inhibited by PLK inhibitors. PLK-dependent signaling may be a new pathway,
which promotes alpha1-adrenergic contraction of prostate smooth muscle cells. As
contractions by endothelin and U46619 are not susceptible to PLK inhibition, this
reflects divergent regulation of adrenergic and non-adrenergic prostate smooth
muscle contraction.
PMID- 29962966
TI - Recent Advances in Placenta-Heart Interactions.
AB - Congenital heart defects (CHD) occur in ~1 in every 100 live births. In addition,
an estimated 10% of fetal loss is due to severe forms of CHD. This makes heart
defects the most frequently occurring birth defect and single cause of in utero
fatality in humans. There is considerable evidence that CHD is heritable,
indicating a strong contribution from genetic risk factors. There are also known
external environmental exposures that are significantly associated with risk for
CHD. Hence, the majority of CHD cases have long been considered to be
multifactorial, or generally caused by the confluence of several risk factors
potentially from genetic, epigenetic, and environmental sources. Consequently, a
specific cause can be very difficult to ascertain, although patterns of
associations are very important to prevention. While highly protective of the
fetus, the in utero environment is not immune to insult. As the conduit between
the mother and fetus, the placenta plays an essential role in maintaining fetal
health. Since it is not a fully-formed organ at the onset of pregnancy, the
development of the placenta must keep pace with the growth of the fetus in order
to fulfill its critical role during pregnancy. In fact, the placenta and the
fetal heart actually develop in parallel, a phenomenon known as the placenta
heart axis. This leaves the developing heart particularly vulnerable to early
placental insufficiency. Both organs share several developmental pathways, so
they also share a common vulnerability to genetic defects. In this article we
explore the coordinated development of the placenta and fetal heart and the
implications for placental involvement in the etiology and pathogenesis of CHD.
PMID- 29962967
TI - Thick Filament Mechano-Sensing in Skeletal and Cardiac Muscles: A Common
Mechanism Able to Adapt the Energetic Cost of the Contraction to the Task.
AB - A dual regulation of contraction operates in both skeletal and cardiac muscles.
The first mechanism, based on Ca2+-dependent structural changes of the regulatory
proteins in the thin filament, makes the actin sites available for binding of the
myosin motors. The second recruits the myosin heads from the OFF state, in which
they are unable to split ATP and bind to actin, in relation to the force during
contraction. Comparison of the relevant X-ray diffraction signals marking the
state of the thick filament demonstrates that the force feedback that controls
the regulatory state of the thick filament works in the same way in skeletal as
in cardiac muscles: even if in an isometric tetanus of skeletal muscle force is
under the control of the firing frequency of the motor unit, while in a heartbeat
force is controlled by the afterload, the stress-sensor switching the motors ON
plays the same role in adapting the energetic cost of the contraction to the
force. A new aspect of the Frank-Starling law of the heart emerges: independent
of the diastolic filling of the ventricle, the number of myosin motors switched
ON during systole, and thus the energetic cost of contraction, are tuned to the
arterial pressure. Deterioration of the thick-filament regulation mechanism may
explain the hyper-contractility related to hypertrophic cardiomyopathy, an
inherited heart disease that in 40% of cases is due to mutations in cardiac
myosin.
PMID- 29962968
TI - The Peritoneum: Beyond the Tissue - A Review.
AB - Background: Despite its complexity, the peritoneum is usually underestimated in
classical medical texts simply as the surrounding tissue (serous membrane) of the
gut. Novel findings on physiology and morphology of the peritoneum and
mesothelial cell exist but they are usually focused or limited to Continuous
Ambulatory Peritoneal Dialysis research and practice. This review aims to expose,
describe and analyze the most recent evidence on the peritoneum's morphology,
embryology and physiology. Materials and Methods: A literature review was
performed on Pubmed and MEDLINE. With no limit of publication date, original
papers and literature reviews about the peritoneum, the peritoneal cavity,
peritoneal fluid, and mesothelial cells were included (n = 72). Results:
Peritoneum develops in close relationship to the gut from an early period in
embryogenesis. Analyzing together the development of the primitive gut and the
surrounding mesothelium helps understanding that the peritoneal cavity, the
mesenteries and other structures can be considered parts of the peritoneum.
However, some authors consider that structures like the mesenteries are different
to the peritoneum. The mesothelial cell has a complex ultrastructural
organization with intercellular junctions and apical microvilli. This complexity
is further proven by the large array of functions like selective fluid and cell
transport; physiological protective barrier; immune induction, modulation, and
inhibition; tissue repair and scarring; preventing adhesion and tumoral
dissemination; cellular migration; and the epithelial-mesenchymal transition
capacity. Conclusion: Recent evidence on the anatomy, histology, and physiology
of the peritoneum, shows that this structure is more complex than a simple serous
membrane. These results call for a new conceptualization of peritoneum, and
highlight the need of adequate research for identifying clinical relevance of
this knowledge.
PMID- 29962969
TI - A Constraint-Based Model Analysis of Enterocyte Mitochondrial Adaptation to
Dietary Interventions of Lipid Type and Lipid Load.
AB - Computational modeling of mitochondrial adaptability and flexibility in the small
intestine upon different nutritional exposures will provide insights that will
help to define healthy diet interventions. Therefore, a murine enterocyte
specific mitochondrial constraint-based metabolic model (named MT_mmuENT127) was
constructed and used to simulate mitochondrial behavior under different dietary
conditions, representing various levels and composition of nutrients absorbed by
the enterocytes in mice, primarily focusing on metabolic pathways. Our
simulations predicted that increasing the fraction of marine fatty acids in the
diet, or increasing the dietary lipid/carbohydrate ratio resulted in (i) an
increase in mitochondrial fatty acid beta oxidation, and (ii) changes in only a
limited subset of mitochondrial reactions, which appeared to be independent of
gene expression regulation. Moreover, transcript levels of mitochondrial proteins
suggested unaltered fusion-fission dynamics by an increased lipid/carbohydrates
ratio or by increased fractions of marine fatty acids. In conclusion, our
enterocytic mitochondrial constraint-based model was shown to be a suitable
platform to investigate effects of dietary interventions on mitochondrial
adaptation and provided novel and deeper insights in mitochondrial metabolism and
regulation.
PMID- 29962970
TI - Hypoxia Induces Changes in AMP-Activated Protein Kinase Activity and Energy
Metabolism in Muscle Tissue of the Oriental River Prawn Macrobrachium nipponense.
AB - Hypoxia has important effects on biological activity in crustaceans, and
modulation of energy metabolism is a crucial aspect of crustaceans' ability to
respond to hypoxia. The adenosine 5'-monophosphate (AMP)-activated protein kinase
(AMPK) enzyme is very important in cellular energy homeostasis; however, little
information is known about the role of AMPK in the response of prawns to acute
hypoxia. In the present study, three subunits of AMPK were cloned from the
oriental river prawn, Macrobrachium nipponense. The full-length cDNAs of the
alpha, beta, and gamma AMPK subunits were 1,837, 3,174, and 3,773 bp long, with
open reading frames of 529, 289, and 961 amino acids, respectively. Primary amino
acid sequence alignment of these three subunits revealed conserved similarity
between the functional domains of the M. nipponense AMPK protein with AMPK
proteins of other animals. The expression of the three AMPK subunits was higher
in muscle tissue than in other tissues. Furthermore, the mRNA expression of
AMPKalpha, AMPKbeta, and AMPKgamma were significantly up-regulated in M.
nipponense muscle tissue after acute hypoxia. Probing with a phospho-AMPKalpha
antibody revealed that AMPK is phosphorylated following hypoxia; this
phosphorylation event was found to be essential for AMPK activation. Levels of
glucose and lactic acid in hemolymph and muscle tissue were significantly changed
over the course of hypoxia and recovery, indicating dynamic changes in energy
metabolism in response to hypoxic stress. The activation of AMPK by hypoxic
stress in M. nipponense was compared to levels of muscular AMP, ADP, and ATP, as
determined by HPLC; it was found that activation of AMPK may not completely
correlate with AMP:ATP ratios in prawns under hypoxic conditions. These findings
confirm that the alpha, beta, and gamma subunits of the prawn AMPK protein are
regulated at the transcriptional and protein levels during hypoxic stress to
facilitate maintenance of energy homeostasis.
PMID- 29962972
TI - Revisiting the Role of Eotaxin-1/CCL11 in Psychiatric Disorders.
AB - Eotaxin-1/CCL11 is a chemokine originally implicated in the selective recruitment
of eosinophils into inflammatory sites during allergic reactions, being
thoroughly investigated in asthma, allergic rhinitis, and other eosinophil
related conditions. Eotaxin-1/CCL11 is also involved with a skewed immune
response toward a type-2 (Th2) profile. In addition to its role in immune
response, recent studies have shown that eotaxin-1/CCL11 is associated with
aging, neurogenesis and neurodegeneration, being able to influence neural
progenitor cells, and microglia. Increased circulating levels of eotaxin-1/CCL11
have been described in major psychiatric disorders (schizophrenia, bipolar
disorder, major depression), sometimes correlating with the severity of
psychopathological and cognitive parameters. As similar findings have been
reported in neurodegenerative conditions such as Alzheimer's disease, it has been
hypothesized that mechanisms involving eotaxin-1/CCL11 signaling may underlie the
"accelerated aging" profile commonly linked to psychiatric disorders. Future
studies must determine whether eotaxin-1/CCL11 can be regarded as a prognostic
biomarker and/or as therapeutic target for resistant/progressive cases.
PMID- 29962973
TI - Markers of Inflammation and Monoamine Metabolism Indicate Accelerated Aging in
Bipolar Disorder.
AB - Background: A mild pro-inflammatory status accompanies bipolar disorder (BD).
Inflammation can cause a shift in monoamine metabolism, thereby activating more
cytotoxic pathways. The extent to which low-grade inflammation in BD interacts
with monoamine metabolism and how this accords to aging and clinical course is
unknown. Objectives: We evaluated the presence of alterations in inflammation and
monoamine metabolism in BD throughout different mood states and the role of aging
therein. Methods: Sixty-seven patients with BD were included during an acute mood
episode, either depressive (n = 29), (hypo)manic (n = 29), or mixed (n = 9).
Plasma levels of inflammatory markers [tumor necrosis factor alpha (TNF-alpha),
interferon gamma (IFN-y), interleukin-6 (IL-6), and C-reactive protein (CRP)] and
markers of monoamine metabolism (neopterin, tryptophan, kynurenine,
phenylalanine, and tyrosine) were measured repeatedly during a follow-up of 8
months. Levels in patients were compared to controls (n = 35) and correlated to
HDRS-17 and YMRS scores. Spearman correlations and linear mixed model analysis
were used for statistical analysis. Results: Forty-nine patients and 30 controls
(age range: 22-62 years) completed the study. No significant differences in
inflammatory markers were found between patients and controls overall.
Tryptophan, tyrosine, and phenylalanine levels were lower in patients. In both
patients and controls, markers of inflammation correlated only weakly with
markers of monoamine metabolism, but correlations representative for activity of
cytotoxic pathways in monoamine metabolism were more pronounced in patients. In
patients, but not in controls, older age was associated with increases in
inflammatory markers (IL-6, CRP, neopterin) and the kynurenine/tryptophan ratio.
None of the biological markers correlated significantly with mood symptom
severity. Conclusion: Our data suggest an increased susceptibility of patients
with BD to develop a pro-inflammatory state and to shift monoamine metabolism
toward more cytotoxic pathways. These findings are in support of the theory of
neuroprogression and accelerated aging in BD. Since associations between
biological markers and clinical characteristics are limited, it remains to be
determined if alterations in biological markers are due to a disease effect or
rather are a consequence of confounding factors.
PMID- 29962971
TI - ER-Mitochondria Microdomains in Cardiac Ischemia-Reperfusion Injury: A Fresh
Perspective.
AB - The mitochondrial and endoplasmic reticulum (ER) homeostasis is pivotal to the
maintenance of an array of physiological processes. The physical contact and
association between ER and mitochondria, known as the ER-mitochondria
microdomains or mitochondria-associated ER membrane (MAM), temporally and
spatially regulates the mitochondria/ER structure and function. More evidence
suggests a role for MAMs in energy production, cellular contraction and mobility,
and normal extracellular signal transmission. In pathological states, such as
cardiac ischemia-reperfusion (I/R injury), this ER-mitochondria microdomains may
act to participate in the cellular redox imbalance, ER stress, mitochondrial
injury, energy deletion, and programmed cell death. From a therapeutic
perspective, a better understanding of the cellular and molecular mechanisms of
the pathogenic ER-mitochondria contact should help to identify potential
therapeutic target for cardiac I/R injury and other cardiovascular diseases and
also pave the road to new treatment modalities pertinent for the treatment of
reperfusion damage in clinical practice. This review will mainly focus on the
possible signaling pathways involved in the regulation of the ER-mitochondria
contact. In particular, we will summarize the downstream signaling modalities
influenced by ER-mitochondria microdomains, for example, mitochondrial fission,
mitophagy, calcium balance, oxidative stress, and programmed cell death in
details.
PMID- 29962974
TI - Estimating Prevalence of Illicit Drug Use in Yunnan, China, 2011-15.
AB - Background and Aims: Yunnan has been one of the provinces most afflicted by
illicit drug use in China. However, there have been few systematic studies on the
prevalence of illicit drug use in the area. Method: Using data on illicit drug
users registered in the police system, this study aims to estimate the population
size of illicit drug users and the annual prevalence of drug use in Yunnan from
2011 to 2015 using Zelterman's capture-recapture method. Results: In the 15-64
year-old population, the estimated prevalence rate of any illicit drug use was
0.81% (0.76-0.86%) in 2011 and 0.94% (0.90-0.98%) in 2014, representing a
significant increase. The prevalence rate of heroin use decreased from 0.67%
(0.63-0.73%) in 2011 to 0.57% (0.53-0.61%) in 2015, while the prevalence rate of
methamphetamine use doubled from 0.20% (0.17-0.24%) in 2011 to 0.48% (0.46-0.50%)
in 2015. The mean age of the 141,702 identified illicit drug users in Yunnan from
2011 to 2015 was 32.2 years, and the majority were male, low educated, and
peasants; nearly half were single and ethnic minorities. The ratio of the number
of identified illicit drug users to the number of hidden users increased from
1:12 in 2011 to 1:5 in 2015. Conclusion: The prevalence of illicit drug use in
Yunnan has been increasing. Although the prevalence of heroin use decreased,
methamphetamine use increased dramatically from 2011 to 2015. Preventive
strategies that are more effective in reducing illicit drug use are urgently
needed in Yunnan.
PMID- 29962975
TI - Unraveling the Genetic and Environmental Relationship Between Well-Being and
Depressive Symptoms Throughout the Lifespan.
AB - Whether well-being and depressive symptoms can be considered as two sides of the
same coin is widely debated. The aim of this study was to gain insight into the
etiology of the association between well-being and depressive symptoms across the
lifespan. In a large twin-design, including data from 43,427 twins between age 7
and 99, we estimated the association between well-being and depressive symptoms
throughout the lifespan and assessed genetic and environmental contributions to
the observed overlap. For both well-being (range 31-47%) and depressive symptoms
(range 49-61%), genetic factors explained a substantial part of the phenotypic
variance across the lifespan. Phenotypic correlations between well-being and
depressive symptoms across ages ranged from -0.34 in childhood to -0.49 in
adulthood. In children, genetic effects explained 49% of the phenotypic
correlation while in adolescents and young adults, genetic effects explained 60
77% of the phenotypic correlations. Moderate to high genetic correlations
(ranging from -0.59 to -0.66) were observed in adolescence and adulthood, while
in childhood environmental correlations were substantial but genetic correlations
small. Our results suggest that in childhood genetic and environmental effects
are about equally important in explaining the relationship between well-being and
depressive symptoms. From adolescence onwards, the role of genetic effects
increases compared to environmental effects. These results provided more insights
into the etiological underpinnings of well-being and depressive symptoms,
possibly allowing to articulate better strategies for health promotion and
resource allocation in the future.
PMID- 29962977
TI - Corrigendum: Resting-State Functional Connectivity in Autism Spectrum Disorders:
A Review.
AB - [This corrects the article on p. 205 in vol. 7, PMID: 28101064.].
PMID- 29962976
TI - Decision Making Deficits in Relation to Food Cues Influence Obesity: A Triadic
Neural Model of Problematic Eating.
AB - In this review article we propose a model of the brain systems, the deficiency of
which may underlie problematic eating. This integrative model is based on studies
that have focused on discrete brain components involved in problematic eating,
combined with insights from studies on the neurocognitive basis of other
addictive and problematic behaviors. The model includes: (a) a hyper-functioning
reward anticipation and processing system (amygdala-striatum dependent) in
response to food-related cues; (b) a hypo-functioning reflective and inhibitory
control system (prefrontal cortex dependent), that fails to anticipate and
properly weigh future outcomes; and (c) an altered interoceptive awareness system
(insular cortex dependent) that translates homeostatic violation signals into a
strong consumption desire that hijacks the inhibitory system and excites the
reward system. We posit that when the abovementioned systems are imbalanced in
such a way that the dopamine axis is hyperactive in relation to food cues and the
inhibitory system is weak, and this is further aggravated by an altered
interoceptive awareness system, people may experience loss of control or
inability to resist tempting/rewarding foods. This loss of control over food
consumption can explain, at least in part, the development of excess weight and
contribute to the obesity epidemic.
PMID- 29962978
TI - Approach and Avoidance During Routine Behavior and During Surprise in a Non
evaluative Task: Surprise Matters and So Does the Valence of the Surprising
Event.
AB - The hypothesis that emotions influence our behavior via emotional action
tendencies is at the core of many emotion theories. According to a strong version
of this hypothesis, these emotional action tendencies are immediate, automatic
(unintentional), stimulus-based and directly linked with specific muscle
movements. Recent evidence, however, provides little empirical support for this
strong version during routine behavior, especially when the task does not require
the evaluation of the stimuli. The present study tested the prediction that
surprise interrupts routine behavior and triggers a threat avoidance response. In
the presence of a threat-related stimulus, avoidance responses are relatively
rapid, and approach responses impeded, even when the interrupted routine behavior
is guided by a non-evaluative task goal. In contrast, approach and avoidance
responses are predicted to be unaffected in the presence of a pleasant surprising
stimulus. To test these predictions, in each trial the participants had to
execute an approach or withdrawal movement depending on the location of a target
stimulus. In the critical trial, either a picture of a pleasant or a threat
related animal was presented as target. Supporting the predictions, the
initiation times for these movements were shorter in response to a threat
relevant than a pleasant surprising stimulus. Additionally, in the presence of a
threat-related surprising stimulus, withdrawal movements were made faster than
approach movements even though the participants performed a non-evaluative task.
Implications and limitations of the present study are discussed.
PMID- 29962979
TI - Promoting the Self-Regulation of Stress in Health Care Providers: An Internet
Based Intervention.
AB - The aim of our internet-based intervention study was to find out whether
healthcare professionals can autonomously down-regulate the stress they
experience at their workplace, using an established self-regulation tool called
Mental Contrasting with Implementation Intentions (MCII). Applying MCII to reduce
stress implied for our participants to repeatedly engage in a mental exercise
that (1) required specifying a wish related to reducing stress, (2) identifying
and imagining its most desired positive outcome, (3) detecting and imagining the
obstacle that holds them back, and (4) coming up with an if-then plan on how to
overcome it. We recruited on-line nurses employed at various health institutions
all over Germany, and randomly assigned participants to one of three groups. In
the MCII group (n = 33), participants were taught how to use this exercise via
email and the participants were asked to engage in the exercise on a daily basis
for a period of 3 weeks. As compared to two control groups, one being a no
treatment control group (n = 35) and the other a modified MCII group (n = 32),
our experimental MCII group showed a reduced stress level and an enhanced work
engagement. We discuss the strengths and weaknesses of the present study as well
as ways to intensify MCII effects on stress reduction.
PMID- 29962980
TI - Taming the Lion: How Perceived Worth Buffers the Detrimental Influence of Power
on Aggression and Conflict.
AB - Contrary to conventional wisdom, there is little empirical evidence that elevated
power, by default, fuels conflict and aggression. Instead, previous studies have
shown that extraneous factors that decrease powerholders' perceived worth, making
powerholders feel inferior or disrespected, seem to be necessary to 'unleash'
power's dark side and trigger aggression and conflict. However, this past work
has largely neglected that power boosts individuals' perceptions of worth, and as
such these variables are not independent. The present research sought to address
this oversight, thereby providing a more nuanced account of how perceived worth
stifles aggression and conflict tendencies in powerholders. Focusing on self
esteem (Study 1) and status (Study 2) as two interrelated facets of perceived
worth, we report primary and secondary data indicating that perceived worth acts
as buffer and counters aggression as well as more general conflict tendencies in
powerholders. By providing evidence for a suppression effect, the present
findings go beyond the moderations identified in prior work and demonstrate that
perceptions of worth are critical to understanding the link between power on the
one hand, and aggression and conflict on the other. We conclude by discussing the
social regulatory function of perceived worth in hierarchical relations.
PMID- 29962981
TI - Understanding and Resolving Failures in Human-Robot Interaction: Literature
Review and Model Development.
AB - While substantial effort has been invested in making robots more reliable,
experience demonstrates that robots operating in unstructured environments are
often challenged by frequent failures. Despite this, robots have not yet reached
a level of design that allows effective management of faulty or unexpected
behavior by untrained users. To understand why this may be the case, an in-depth
literature review was done to explore when people perceive and resolve robot
failures, how robots communicate failure, how failures influence people's
perceptions and feelings toward robots, and how these effects can be mitigated.
Fifty-two studies were identified relating to communicating failures and their
causes, the influence of failures on human-robot interaction (HRI), and
mitigating failures. Since little research has been done on these topics within
the HRI community, insights from the fields of human computer interaction (HCI),
human factors engineering, cognitive engineering and experimental psychology are
presented and discussed. Based on the literature, we developed a model of
information processing for robotic failures (Robot Failure Human Information
Processing, RF-HIP), that guides the discussion of our findings. The model
describes the way people perceive, process, and act on failures in human robot
interaction. The model includes three main parts: (1) communicating failures, (2)
perception and comprehension of failures, and (3) solving failures. Each part
contains several stages, all influenced by contextual considerations and
mitigation strategies. Several gaps in the literature have become evident as a
result of this evaluation. More focus has been given to technical failures than
interaction failures. Few studies focused on human errors, on communicating
failures, or the cognitive, psychological, and social determinants that impact
the design of mitigation strategies. By providing the stages of human information
processing, RF-HIP can be used as a tool to promote the development of user
centered failure-handling strategies for HRIs.
PMID- 29962982
TI - Effect of Varying Levels of Glare on Contrast Sensitivity Measurements of Young
Healthy Individuals Under Photopic and Mesopic Vision.
AB - Contrast sensitivity (CS), the ability to detect small spatial changes of
luminance, is a fundamental aspect of vision. However, while visual acuity is
commonly measured in eye clinics, CS is often not assessed. At issue is that
tests of CS are not highly standardized in the field and that, in many cases,
optotypes used are not sensitive enough to measure graduations of performance and
visual abilities within the normal range. Here, in order to develop more
sensitive measures of CS, we examined how CS is affected by different
combinations of glare and ambient lighting in young healthy participants. We
found that low levels of glare have a relatively small impact on vision under
both photopic and mesopic conditions, while higher levels had significantly
greater consequences on CS under mesopic conditions. Importantly, we found that
the amount of glare induced by a standard built-in system (69 lux) was
insufficient to induce CS reduction, but increasing to 125 lux with a custom
system did cause a significant reduction and shift of CS in healthy individuals.
This research provides important data that can help guide the use of CS measures
that yield more sensitivity to characterize visual processing abilities in a
variety of populations with ecological validity for non-ideal viewing conditions
such as night time driving.
PMID- 29962983
TI - Multitasking During Simulated Car Driving: A Comparison of Young and Older
Persons.
AB - Human multitasking is typically studied by repeatedly presenting two tasks,
either sequentially (task switch paradigms) or overlapping in time (dual-task
paradigms). This is different from everyday life, which typically presents an
ever-changing sequence of many different tasks. Realistic multitasking therefore
requires an ongoing orchestration of task switching and dual-tasking. Here we
investigate whether the age-related decay of multitasking, which has been
documented with pure task-switch and pure dual-task paradigms, can also be
quantified with a more realistic car driving paradigm. 63 young (20-30 years of
age) and 61 older (65-75 years of age) participants were tested in an immersive
driving simulator. They followed a car that occasionally slowed down and
concurrently executed a mixed sequence of loading tasks that differed with
respect to their sensory input modality, cognitive requirements and motor output
channel. In two control conditions, the car-following or the loading task were
administered alone. Older participants drove more slowly, more laterally and more
variably than young ones, and this age difference was accentuated in the
multitask-condition, particularly if the loading task took participants' gaze and
attention away from the road. In the latter case, 78% of older drivers veered off
the road and 15% drove across the median. The corresponding values for young
drivers were 40% and 0%, respectively. Our findings indicate that multitasking
deteriorates in older age not only in typical laboratory paradigms, but also in
paradigms that require orchestration of dual-tasking and task switching. They
also indicate that older drivers are at a higher risk of causing an accident when
they engage in a task that takes gaze and attention away from the road.
PMID- 29962985
TI - Creativity, Proactive Personality, and Entrepreneurial Intention: The Role of
Entrepreneurial Alertness.
AB - This study examines the extent to which entrepreneurial alertness mediates the
effects of students' proactive personalities and creativity on entrepreneurial
intention. Drawing on a field survey of 735 Chinese undergraduates at 26
universities, this study provides evidence for the argument that entrepreneurial
alertness has a fully mediation effect on the relationship between creativity, a
proactive personality, and entrepreneurial intention. The findings shed light on
the mechanisms that underpin entrepreneurial alertness and contribute to the
literature on key elements of the entrepreneurial process.
PMID- 29962986
TI - Short Is Beautiful: Dimensionality and Measurement Invariance in Two Length of
the Basic Psychological Need Satisfaction at Work Scale.
AB - Self-determination theory proposes that all humans have three intrinsic
psychological needs: the needs for Autonomy, Competence, and Relatedness. These
needs take different forms in different areas of life. The present study examines
the psychometric properties of a Swedish version of the Basic Psychological Need
Satisfaction at Work (BPNS-W) scale. The fit of 10-factor structures previously
suggested for related versions of the scale were compared. Cross-sectional data
from 1,200 participants were examined in a confirmatory factor analysis
framework. Both the original 21-item version and a reduced 12-item version of the
BPNS-W were examined. The General Health Questionnaire was used for validation.
The results supported a three-factor solution with correlated error variances for
the reversed items. Invariance testing of the long and short scales gave best
support to the short scale, for which partial scalar invariance was achieved. The
external validity of the short scale was supported by a hierarchical regression
analysis in which each need made a unique contribution in predicting
psychological well-being. In conclusion, the results corroborate a three-factor
structure of BPNS-W. Although not perfect the short scale should, it is argued,
be preferred over the long version. Directions for the future development of the
scale are discussed.
PMID- 29962984
TI - Examining Brain Structures Associated With Emotional Intelligence and the
Mediated Effect on Trait Creativity in Young Adults.
AB - Little is known about the association between emotional intelligence (EI) and
trait creativity (TC), and the brain structural bases which involves. This study
investigated the neuroanatomical basis of the association between EI and TC which
measured by the Schutte self-report EI scale and the Williams creativity aptitude
test. First, the voxel-based morphometry (VBM) analysis was used to explore the
brain structures which is closely related to EI in a large young sample (n =
213). The results showed that EI was positively correlated with the regional gray
matter volume (rGMV) in the right orbitofrontal cortex (OFC), which is regarded
as a key region of emotional processing. More importantly, further mediation
analysis revealed that rGMV in the right OFC partially mediated the association
between EI and TC, which showed the OFC volume could account for the relationship
between EI and TC. These findings confirmed the close relationship between EI and
TC, and highlighted that the brain volumetric variation in the OFC associated
with the top-down processing of emotion regulation, which may play a critical
role in the promotion of TC. Together, these findings contributed to sharpening
the understanding of the complex relationship between EI and TC from the
perspective of brain structural basis.
PMID- 29962987
TI - Eye Movement Desensitization and Reprocessing Integrative Group Treatment
Protocol (EMDR-IGTP) Applied to Caregivers of Patients With Dementia.
AB - Caregivers of patients with dementia experience high levels of stress and burden,
with effects comparable to those of a traumatic event. Eye Movement
Desensitization and Reprocessing (EMDR) appear to be effective in recovering post
traumatic stress disorder (PTSD). We aimed at investigating the effectiveness of
the Eye Movement Desensitization and Reprocessing Integrative Group Treatment
Protocol (EMDR-IGTP) on the "caregiver syndrome". Forty-four primary caregivers
entered the study. They were randomly assigned to either the "immediate" branch,
who received the treatment soon after recruitment, or to the "delayed" branch,
who received it two months after recruitment. The treatment consisted of eight
group sessions (one per week) spanning over two months. Emotional distress was
measured before the treatment, immediately after the end of it, and two months
later (follow-up), by means of several clinical scales (Impact of Event Scale
Revised, IES-R; Caregiver Needs Assessment, CNA; Caregiver Burden Inventory, CBI;
Anxiety and Depression Scale-Reduced Form, AD-R). The "immediate" branch improved
significantly more than the "delayed" (control) branch on The Impact of Event
Scale-Revised, the Anxiety, and the Depression scales; however, after treatment
such an improvement was maintained only in the first scale. The "delayed" branch
took less advantage of the treatment, showing significant reduction only on the
Depression scale, an effect which disappeared at follow-up. These preliminary
results show for the first time that EMDR-IGTP reduces stress-related symptoms,
anxiety, and depression in caregivers of patients with dementia. Interestingly,
caregivers who were inserted in a waiting list after recruitment showed smaller
treatment effects. Larger samples are needed to better interpret such
differential clinical profiles.
PMID- 29962988
TI - The Human-Nature Experience: A Phenomenological-Psychoanalytic Perspective.
AB - Drawing upon phenomenology and psychoanalytic concepts, we explore and explicate
participants' lived experience of the natural world. The authors draw upon
Husserl's description of consciousness as intentionality and his later work on
the life-world, in exploring experiences which provide a basis for a
psychochoanalytic understanding of the human-nature experience. Unstructured
interviews were undertaken with nine participants, each of whom regarded nature
as being significant for their sense of wellbeing. The lived experiences were
explicated drawing upon the two processes: Giorgi's descriptive phenomenological
psychological methodology and psychoanalytic researcher reflexivity. Data
analysis and explication involved the following steps: (1) a thorough reading of
each interview transcript, (2) breaking data into parts by demarcating meaning
units, (3) organizing data by translating meaning units into units of
psychological experience through coding, and (4) arriving at a summary of the
data which involved organizing and reviewing units of psychological experience.
The process of reflection led to the formulation of an essential psychological
structure of participants' lived experience of the natural world. We argue that
the human-nature relationship can be conceived in terms of psychoanalytic
concepts, and in particular, constructs based upon an understanding of the
primacy of attachment relationships. The natural world is elucidated as (a)
nature being experienced as a primary attachment, (b) nature experienced as a
secure base, (c) nature experienced as twinship, (d) nature experienced as
containing, and (e) nature experienced as embodied. This paper extends previous
empirical descriptions of the human-nature relationship by incorporating
psychoanalytic processes and theory into a theoretically informed qualitative
methodological stance. Beyond the traditional notion of nature as something 'out
there' that we can interact with for cognitive or emotional restoration,
participants in this study described the experience of nature as being integral
to their sense of self. This study suggests that experiences that facilitate
immersion in nature provide opportunities for the development of an integrated
sense of self that has a profound impact on a participant's sense of wellbeing.
The findings further demonstrate the convergence between phenomenology and
psychoanalytic constructs which offers a richness to our understanding the
subjectivity of participants and their relationship with nature, a perspective
not often attainable through more traditional quantitative research
methodologies.
PMID- 29962989
TI - A Hierarchical Taxonomy of Test Validity for More Flexibility of Validation.
AB - Test validity lies at the core of educational and psychological testing, but
there are controversies about what test validity is and how test validation
should proceed. This paper develops a taxonomy to redefine test validity with
hierarchical levels. On the basis of testing foundation, the hierarchy includes
operational, measurable, realizable, and useful levels, which result in testing
consequence. With the help of a context-specific construct, different levels of
test validity, and different types of score use, the proposed taxonomy offers
more flexibility for test validation. It can also shed light on the
interpretations of important testing concepts and help streamline test
development. Real-life examples are given to demonstrate the usefulness of the
taxonomy across different settings.
PMID- 29962990
TI - Development and Validation of Two Short Forms of the Managing the Emotions of
Others (MEOS) Scale.
AB - The 58-item MEOS assesses managing the emotions of others, a component of trait
emotional intelligence (EI). Managing another person's emotions can be used with
the intention of helping the target but also in a strategically manipulative
manner; the subscales of the MEOS cover both these aspects of emotion management.
In order to allow researchers to access shorter versions of the MEOS for use in
studies where administering the full-length scale is not feasible, two short
forms of the MEOS with six (MEOS-SF) and four (MEOS-VSF) items per sub-scale were
developed and validated. Study 1 used factor analysis of pre-existing MEOS item
data to select items for the short forms and also compared the bivariate
correlations of the MEOS, MEOS-SF and MEOS-VSF with personality and global trait
EI. Study 2 examined the MEOS-SF and MEOS-VSF in two new samples (N = 394/226).
The results from both studies showed that the short forms had good psychometric
properties and associations similar to those of the full-length MEOS with
personality, global trait EI, and other measures. The MEOS-SF and MEOS-VSF are
hence suitable for use in contexts where a brief assessment of the full range of
the domain of managing the emotions of others is required. The availability of
short subscales assessing the manipulative facets of the MEOS is especially
relevant to the emerging area of "dark side" trait EI research.
PMID- 29962991
TI - Beyond Verbal Behavior: An Empirical Analysis of Speech Rates in Psychotherapy
Sessions.
AB - Objective: The present work aims to detect the role of the rate of speech as a
mechanism able to give information on patient's intrapsychic activity and the
intersubjective quality of the patient-therapist relationship. Method: Thirty
clinical sessions among five patients were sampled and divided into idea units (N
= 1276) according to the referential activity method. Each idea unit was rated
according to referential activity method and in terms of speech rate (syllables
per second) for both patient and therapist. A mixed-effects model was applied in
order to detect the relationship between the speech rate of both the patient and
the therapist and the features of the patient's verbal production in terms of
referential activity scales. A Pearson correlation was applied to evaluate the
synchrony between the speech rate of the patient and the therapist. Results:
Results highlight that speech rate varies according patient's ability to get in
touch with specific aspects detected through referential activity method: patient
and the therapist speech rate get synchronized during the course of the sessions;
and the therapist's speech rate partially attunes to the patient's ability to get
in touch with inner aspects detected through RA method. Conclusion: The work
identified speech rate as a feature that may help in the development of the
clinical process in light of its ability to convey information about a patient's
internal states and a therapist's attunement ability. These results support the
intersubjective perspective on the clinical process.
PMID- 29962992
TI - Cyber Victimization Is Associated With Eating Disorder Psychopathology in
Adolescents.
AB - Introduction: Technology is constantly evolving in a vast number of fields. In
this way, cyber victimization is associated with psychopathology, and body
appearance is a primary target of cyberbullies. Thus, the literature demonstrates
a clear association between bullying and unhealthy eating behaviors in
adolescents. However, studies that have examined the association between cyber
victimization and eating disorder psychopathology are scarce. Objective: (1) To
analyze whether there are differences in the cyber victimization scores depending
on the gender, controlling for age; (2) to analyze whether cyber victimization is
negatively associated with eating disorder psychopathology; (3) to analyze
whether this association is moderated by the level of Appearance Evaluation.
Method: Participants in the present study included 676 adolescents, 367 girls and
309 boys from several cities of Spain. The mean age for the overall sample was
14.28 years (SD = 1.65), ranging from 12 to 19. The participants filled out the
questionnaires ECIPQ, MBSRQ, and EAT. Results: Cyber victimization was associated
with eating disorders psychopathology, Appearance Evaluation, and Overweight
Preoccupation. Appearance Evaluation moderated the association between Cyber
victimization and the eating disorder psychopathology. Conclusion: It is
necessary to assess vulnerability to eating disorders in adolescents who have
been victims of cyberbullying.
PMID- 29962993
TI - Reach-To-Grasp Movements: A Multimodal Techniques Study.
AB - The aim of the present study was to investigate the correlation between
corticospinal activity, kinematics, and electromyography (EMG) associated with
the execution of precision and whole-hand grasps (WHGs). To this end, motor
evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS), EMG,
and 3-D motion capture data have been simultaneously recorded during the planning
and the execution of prehensile actions toward either a small or a large object.
Differences in the considered measures were expected to distinguish between the
two types of grasping actions both in terms of action preparation and execution.
The results indicate that the index finger (FDI) and the little finger (ADM)
muscles showed different activation patterns during grasping execution, but only
the FDI appeared to distinguish between the two types of actions during motor
preparation. Kinematics analysis showed that precision grips differed from WHGs
in terms of displayed fingers distance when shaping before object's contact, and
in terms of timing and velocity patterns. Moreover, significant correlations
suggest a relationship between the muscular activation and the temporal aspects
concerned with the index finger's extension during whole-hand actions. Overall,
the present data seem to suggest a crucial role played by index finger as an
early "marker" of differential motor preparation for different types of grasps
and as a "navigator" in guiding whole-hand prehensile actions. Aside from the
novelty of the methodological approach characterizing the present study, the data
provide new insights regarding the level of crosstalk among different levels
concerned with the neuro-behavioral organization of reach-to-grasp movements.
PMID- 29962994
TI - Probabilistic-Input, Noisy Conjunctive Models for Cognitive Diagnosis.
AB - Existing cognitive diagnosis models conceptualize attribute mastery status
discretely as either mastery or non-mastery. This study proposes a different
conceptualization of attribute mastery as a probabilistic concept, i.e., the
probability of mastering a specific attribute for a person, and developing a
probabilistic-input, noisy conjunctive (PINC) model, in which the probability of
mastering an attribute for a person is a parameter to be estimated from data. And
a higher-order version of the PINC model is used to consider the associations
among attributes. The results of simulation studies revealed a good parameter
recovery for the new models using the Bayesian method. The Examination for the
Certificate of Proficiency in English (ECPE) data set was analyzed to illustrate
the implications and applications of the proposed models. The results indicated
that PINC models had better model-data fit, smaller item parameter estimates, and
more refined estimates of attribute mastery.
PMID- 29962995
TI - Commentary: Are groups more or less than the sum of their members? The moderating
role of individual identification.
PMID- 29962996
TI - PRIMIR on Tone.
PMID- 29962997
TI - Erratum: Effects of social gaze on visual-spatial imagination.
AB - [This corrects the article on p. 671 in vol. 5, PMID: 25071645.].
PMID- 29962998
TI - Vascular Parkinsonism: Still Looking for a Diagnosis.
PMID- 29962999
TI - Effects of Oligosaccharides From Morinda officinalis on Gut Microbiota and
Metabolome of APP/PS1 Transgenic Mice.
AB - Alzheimer's disease (AD), a progressive neurodegenerative disorder, lacks
preclinical diagnostic biomarkers and therapeutic drugs. Thus, earlier
intervention in AD is a top priority. Studies have shown that the gut microbiota
influences central nervous system disorders and that prebiotics can improve the
cognition of hosts with AD, but these effects are not well understood.
Preliminary research has shown that oligosaccharides from Morinda officinalis
(OMO) are a useful prebiotic and cause substantial memory improvements in animal
models of AD; however, the mechanism is still unclear. Therefore, this study was
conducted to investigate whether OMO are clinically effective in alleviating AD
by improving gut microbiota. OMO were administered to APP/PS1 transgenic mice,
and potential clinical biomarkers of AD were identified with metabolomics and
bioinformatics. Behavioral experiments demonstrated that OMO significantly
ameliorated the memory of the AD animal model. Histological changes indicated
that OMO ameliorated brain tissue swelling and neuronal apoptosis and
downregulated the expression of the intracellular AD marker Abeta1-42. 16S rRNA
sequencing analyses indicated that OMO maintained the diversity and stability of
the microbial community. The data also indicated that OMO are an efficacious
prebiotic in an animal model of AD, regulating the composition and metabolism of
the gut microbiota. A serum metabolomics assay was performed using UHPLC-LTQ
Orbitrap mass spectrometry to delineate the metabolic changes and potential early
biomarkers in APP/PS1 transgenic mice. Multivariate statistical analysis showed
that 14 metabolites were significantly upregulated, and 8 metabolites were
downregulated in the model animals compared to the normal controls. Thus, key
metabolites represent early indicators of the development of AD. Overall, we
report a drug and signaling pathway with therapeutic potential, including
proteins associated with cognitive deficits in normal mice or gene mutations that
cause AD.
PMID- 29963000
TI - Incidence, Risk Factors and Consequences of Epilepsy-Related Injuries and
Accidents: A Retrospective, Single Center Study.
AB - Introduction: This study was designed to evaluate risk factors and incidence of
epilepsy-related injuries and accidents (ERIA) at an outpatient clinic of a
German epilepsy center providing healthcare to a mixed urban and rural population
of over one million inhabitants. Methods: Data acquisition was performed between
10/2013 and 09/2014 using a validated patient questionnaire on socioeconomic
status, course of epilepsy, quality of life (QoL), depression, injuries and
accidents associated with seizures or inadequate periictal patterns of behavior
concerning a period of 3 months. Univariate analysis, multiple testing and
regression analysis were performed to identify possible variables associated with
ERIA. Results: A total of 292 patients (mean age 40.8 years, range 18-86; 55%
female) were enrolled and analyzed. Focal epilepsy was diagnosed in 75% of the
patients. The majority was on an antiepileptic drug (AEDs) polytherapy (mean
number of AEDs: 1.65). Overall, 41 patients (14.0%) suffered from epilepsy
related injuries and accidents in a 3-month period. Besides lacerations (n = 18,
6.2%), abrasions and bruises (n = 9, 3.1%), fractures (n = 6, 2.2%) and burns (n
= 3, 1.0%), 17 mild injuries (5.8%) were reported. In 20 (6.8% of the total
cohort) cases, urgent medical treatment with hospitalization was necessary.
Epilepsy-related injuries and accidents were related to active epilepsy,
occurrence of generalized tonic-clonic seizures (GTCS) and drug-refractory course
as well as reported ictal falls, ictal loss of consciousness and abnormal peri
ictal behavior in the medical history. In addition, patients with ERIA had
significantly higher depression rates and lower QoL. Conclusion: ERIA and their
consequences should be given more attention and standardized assessment for ERIA
should be performed in every outpatient visit.
PMID- 29963001
TI - Systemic Acrolein Elevations in Mice With Experimental Autoimmune
Encephalomyelitis and Patients With Multiple Sclerosis.
AB - Demyelination and axonal injury are the key pathological processes in multiple
sclerosis (MS), driven by inflammation and oxidative stress. Acrolein, a
byproduct and instigator of oxidative stress, has been demonstrated as a
neurotoxin in experimental autoimmune encephalomyelitis (EAE), an animal model of
MS. However, due to the invasive nature of acrolein detection using
immunoblotting techniques, the investigation of acrolein in MS has been limited
to animal models. Recently, detection of a specific acrolein-glutathione
metabolite, 3-HPMA, has been demonstrated in urine, enabling the noninvasive
quantification of acrolein for the first time in humans with neurological
disorders. In this study, we have demonstrated similar elevated levels of
acrolein in both urine (3-HPMA) and in spinal cord tissue (acrolein-lysine
adduct) in mice with EAE, which can be reduced through systemic application of
acrolein scavenger hydralazine. Furthermore, using this approach we have
demonstrated an increase of 3-HPMA in both the urine and serum of MS patients
relative to controls. It is expected that this noninvasive acrolein detection
could facilitate the investigation of the role of acrolein in the pathology of MS
in human. It may also be used to monitor putative therapies aimed at suppressing
acrolein levels, reducing severity of symptoms, and slowing progression as
previously demonstrated in animal studies.
PMID- 29963003
TI - Intermittent Hypoxia Induced Formation of "Endothelial Cell-Colony Forming Units
(EC-CFUs)" Is Affected by ROS and Oxidative Stress.
AB - Intermittent hypoxia (IH)-the hallmark of obstructive sleep apnea (OSA)-increases
leukocyte activation, production of NADPH-oxidase dependent reactive oxygen
species (ROS) and oxidative stress, affecting endothelial function. However, IH
and oxidative stress can also stimulate adaptive-protective mechanisms by
inducing the development of Endothelial Cell-Colony Forming Units (EC-CFUs),
which are considered as a good surrogate marker for endothelial progenitor cells
(EPCs), and likely reflect a reparatory response to vascular damage or tissue
ischemia by leukocytes. Blood samples were obtained from 15 healthy consenting
volunteers to evaluate the effects of IH and sustained hypoxia (SH) in vitro on
EC-CFUs development and functions. The variables measured included: their
numbers, the area, the proliferative capacity and ROS production. Additionally,
NADPH-oxidase, VEGF and nuclear factor-erythroid 2 related factor 2 (Nrf2)
expression, as well as their paracrine effects on endothelial tube formation were
determined. The involvement of ROS was probed using the anti-oxidant N
acetylcysteine (NAC) and NADPH-oxidase inhibitors apocynin and diphenyl-iodide.
Compared to normoxia, IH-dependent increases in EC-CFUs numbers were observed,
showing an individual donor-dependent trait. Also, the expression of VEGF and
gp91phox, a subunit of NADPH-oxidase, were significantly increased. ROS
production and oxidative stress markers were also significantly increased, but
Nrf2 expression and colony size were unaffected by IH. Additionally, conditioned
media harvested from IH- and SH-treated mature EC-CFUs, significantly increased
endothelial tube formation. These effects were markedly attenuated or diminished
by the ROS and NADPH-oxidase inhibitors employed. In conclusion, we show here for
the first time that IH-associated oxidative stress promotes EC-CFUs' vascular and
paracrine capacities through ROS. However, the large inter-individual variability
expressed in EC-CFUs numbers and functions to a given IH stimulus, may represent
an individual trait with a potential clinical significance.
PMID- 29963004
TI - Changes in Dynamics Within and Between Resting-State Subnetworks in Juvenile
Myoclonic Epilepsy Occur at Multiple Frequency Bands.
AB - Time-varying connectivity analyses have indicated idiopathic generalized epilepsy
(IGE) could cause significant abnormalities in dynamic connective pattern within
and between resting-state sub-networks (RSNs). However, previous studies mainly
focused on the IGE-induced dynamic changes of functional connectivity (FC) in
specific frequency band (0.01-0.08 Hz or 0.01-0.15 Hz), ignoring the changes
across different frequency bands. Here, 24 patients with IGE characterized by
juvenile myoclonic epilepsy (JME) and 24 matched healthy controls were studied
using a data-driven frequency decomposition approach and a sliding window
approach. The RSN dynamics, including intra-RSN dynamics and inter-RSN dynamics,
was further calculated to investigate dynamic FC changes within and between RSNs
in JME patients in each decomposed frequency band. Compared to healthy controls,
JME patients not only showed frequency-dependent decrease in intra-RSN dynamics
within multiple RSNs but also exhibited fluctuant alterations in inter-RSN
dynamics among several RSNs over different frequency bands especially in the
ventral/dorsal attention network and the subcortical network. Additionally, the
disease severity had significantly negative correlations with both intra-RSN
dynamics within the subcortical network and inter-RSN dynamics between the
subcortical network and the default network at the lower frequency band (0.0095
0.0195 Hz). These results suggested that abnormal dynamic FC within and between
RSNs in JME occurs at multiple frequency bands and the lower frequency band
(0.0095-0.0195 Hz) was probably more sensitive to JME-caused dynamic FC
abnormalities. The frequency subdivision and selection are potentially helpful
for detecting particular changes of dynamic FC in JME.
PMID- 29963005
TI - A Craniopharyngioma Associated With Elevated Cerebrospinal Fluid HCG
Concentrations Misdiagnosed as a Germinoma.
AB - Craniopharyngiomas and germinomas are both rare cranial tumors that most commonly
present during childhood or adolescence. Although these tumors have different
origins, their clinical and radiological features may be similar. In this
article, we report the case of a 35-year female patient with clinical and
radiological findings and increased human chorionic gonadotrophin (HCG) levels in
the cerebrospinal fluid (CSF) that were consistent with a germinoma. However,
pathological analysis revealed a craniopharyngioma. This case report indicates
that HCG, which is regarded as a specific tumor marker for germinomas in the
differential diagnosis of intracranial lesions, is also detectable in other kinds
of suprasellar tumors, such as craniopharyngiomas.
PMID- 29963002
TI - MicroRNA Signature of Traumatic Brain Injury: From the Biomarker Discovery to the
Point-of-Care.
AB - Traumatic brain injury (TBI) is a serious problem that causes high morbidity and
mortality around the world. Currently, no reliable biomarkers are used to assess
the severity and predict the recovery. Many protein biomarkers were extensively
studied for diagnosis and prognosis of different TBI severities such as S
100beta, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE),
neurofilament light chain (NFL), cleaved tau protein (C-tau), and ubiquitin C
terminal hydrolase-L1 (UCH-L1). However, none of these candidates is currently
used in the clinical practice, due to relatively low sensitivity, for the
diagnosis of mild TBI (mTBI) or mild to moderate TBI (MMTBI) patients who are
clinically well and do not have a detectable intracranial pathology on the scans.
MicroRNAs (miRNAs or miRs) are a class of small endogenous molecular regulators,
which showed to be altered in different pathologies, including TBI and for this
reason, their potential role in diagnosis, prognosis and therapeutic
applications, is explored. Promising miRNAs such as miR-21, miR-16 or let-7i were
identified as suitable candidate biomarkers for TBI and can differentiate mild
from severe TBI. Also, they might represent new potential therapeutic targets.
Identification of miRNA signature in tissue or biofluids, for several
pathological conditions, is now possible thanks to the introduction of new high
throughput technologies such as microarray platform, Nanostring technologies or
Next Generation Sequencing. This review has the aim to describe the role of
microRNA in TBI and to explore the most commonly used techniques to identify
microRNA profile. Understanding the strengths and limitations of the different
methods can aid in the practical use of miRNA profiling for diverse clinical
applications, including the development of a point-of-care device.
PMID- 29963006
TI - Multimodality Image Post-processing in Detection of Extratemporal MRI-Negative
Cortical Dysplasia.
AB - Purpose: To determine the diagnostic value of individual image post-processing
techniques in a series of patients who underwent extratemporal operations for
histologically proven, MRI-negative focal cortical dysplasia (FCD). Methods: The
morphometric analysis program (MAP), PET/MRI co-registration and statistical
parametric mapping (SPM) analysis of PET (SPM-PET) techniques were analyzed in 33
consecutive patients. The epileptogenic zone (EZ) assumed by MAP, PET/MRI, and
SPM-PET was compared with the location of the FCD lesions determined by
stereoelectroencephalography (SEEG) and histopathological study. The detection
rate of each modality was statistically compared. Results: Three lesions were
simultaneously detected by the three post-processing methods, while two lesions
were only MAP positive, and 8 were only PET/MRI positive. The detection rate of
MAP, PET/MRI, SPM-PET and the combination of the three modalities was 24.2, 90.9,
57.6, and 97.0%, respectively. Taking the pathological subtype into account, no
type I lesions were detected by MAP, and PET/MRI was the most sensitive method
for detecting FCD types II and IIA. During a mean follow-up period of 22.94
months, seizure freedom was attained in 26/33 patients (78.8%) after focal
corticectomy. Conclusions: MAP, PET/MRI, and SPM-PET provide complementary
information for FCD detection, intracranial electrode design, and lesion
resection. PET/MRI was particularly useful, with the highest detection rate of
extratemporal MRI-negative FCD.
PMID- 29963007
TI - Strengthening Health Systems for Persons With Traumatic Spinal Cord Injury in
South Africa and Sweden: A Protocol for a Longitudinal Study of Processes and
Outcomes.
AB - Background: The provision of specialized care in a time-sensitive manner has
shown to be crucial for survival and recovery of functioning after a traumatic
spinal cord injury (TSCI). However, little is known about the provision of TSCI
care in different international contexts; information which is required for
strengthening policy and practice. Aims: The overarching aim of this study will
be to explore health care processes and outcomes of TSCI care in South Africa and
Sweden. Specific aims will be to: (1) describe acute processes of TSCI care, (2)
determine acute- and long-term outcomes of TSCI care, and (3) identify predictors
for survival, secondary complications, and functioning 12 months post-injury.
Methods: A prospective (regional), population-based cohort study where adults
with an acute TSCI will be recruited over at least a 1-year period from the City
of Cape Town, South Africa, and Stockholm, Sweden. The anticipated sample size
inclusive of both international contexts will be 200 participants-based on a
power calculation for detecting differences in mortality. Information on the
nature and timing of processes of acute care (e.g., transfer logistics, spinal
surgery, and specialized SCI care) will be collected on acute care admission and
discharge using a standardized form. Survival status, secondary complications,
neurological symptoms, functional status, activity, and participation as well as
health-related quality of life will be collected at discharge from SCI acute care
and at 12-months post-injury. Secondary complications and functioning will be
compared between South Africa and Sweden using inferential statistics. To address
mortality specifically, the indirect standardization method for differences in
mortality between contexts will be used whereby Stockholm will serve as standard
for specialize care. For the assessment of factors related to mortality and other
outcomes (e.g., neurological and secondary health conditions) multivariate
regression analyses will be used to determine independent risk factors.
Conclusion: This study offers a unique investigation of the relationship between
health care processes and outcomes of TSCI care with the aim of strengthening
management guidelines for SCI in South Africa and Sweden.
PMID- 29963008
TI - Neuroanatomy of Shared Conversational Laughter in Neurodegenerative Disease.
AB - Perceiving another person's emotional expression often sparks a corresponding
signal in the observer. Shared conversational laughter is a familiar example.
Prior studies of shared laughter have made use of task-based functional
neuroimaging. While these methods offer insight in a controlled setting, the
ecological validity of such controlled tasks has limitations. Here, we
investigate the neural correlates of shared laughter in patients with one of a
variety of neurodegenerative disease syndromes (N = 75), including Alzheimer's
disease (AD), behavioral variant frontotemporal dementia (bvFTD), right and left
temporal variants of semantic dementia (rtvFTD, svPPA), nonfluent/agrammatic
primary progressive aphasia (nfvPPA), corticobasal syndrome (CBS), and
progressive supranuclear palsy (PSP). Patients were recorded in a brief
unrehearsed conversation with a partner (e.g., a friend or family member).
Laughter was manually labeled, and an automated system was used to assess the
timing of that laughter relative to the partner's laughter. The probability of
each participant with neurodegenerative disease laughing during or shortly after
his or her partners' laughter was compared to differences in brain morphology
using voxel-based morphometry, thresholded based on cluster size and a
permutation method and including age, sex, magnet strength, disease-specific
atrophy and total intracranial volumes as covariates. While no significant
correlations were found at the critical T value, at a corrected voxelwise
threshold of p < 0.005, a cluster in the left posterior cingulate gyrus
demonstrated a trend at p = 0.08 (T = 4.54). Exploratory analysis with a
voxelwise threshold of p = 0.001 also suggests involvement of the left precuneus
(T = 3.91) and right fusiform gyrus (T = 3.86). The precuneus has been previously
implicated in the detection of socially complex laughter, and the fusiform gyrus
has a well-described role in the recognition and processing of others' emotional
cues. This study is limited by a relatively small sample size given the number of
covariates. While further investigation is needed, these results support our
understanding of the neural underpinnings of shared conversational laughter.
PMID- 29963009
TI - Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in
Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation.
AB - Several studies have reported that human umbilical cord-derived mesenchymal
stromal cells (UC-MSCs) restore neurological damage in vivo through their
secretion of paracrine factors. We previously found that UC-MSCs attenuate brain
injury by secreting neurotrophic factors, such as brain-derived neurotrophic
factor (BDNF) and hepatocyte growth factor (HGF). However, how these factors
contribute to neuroprotection remains unknown. In this study, we aimed to
investigate to what extent UC-MSC-derived HGF and BDNF contribute to
neuroprotection using a Transwell co-culture system of neonatal cortical neurons
damaged by oxygen-glucose deprivation. The influence of HGF and BDNF were
determined by investigating neurons in both the presence and absence of UC-MSCs
as these cells consistently secrete both factors and can be blocked by
neutralizing antibodies. In the co-culture, UC-MSCs significantly improved
neuronal injury, as indicated by an increase in immature neuron number, neurite
outgrowth, and cell proliferation. Co-culture of damaged neurons with UC-MSCs
also exhibited a reduction in the number of neurons displaying signs of
apoptosis/necrosis. The neuroprotective actions of UC-MSCs were partially
reverted by neutralizing antibodies. Together, our findings reveal that UC-MSC
secreted HGF and BDNF have neuroprotective effects on damaged neurons. Further
studies should address the existence of other potential neurotrophic paracrine
factors.
PMID- 29963010
TI - Steroids and Brain, a Rising Bio-Medical Domain: a Perspective.
AB - Some newly described steroid-related compounds, also found in the rest of the
body, are formed and active in the central nervous system, particularly in the
brain. Some are of pharmacological and physiopathological interest. We
specifically report on two compounds, "MAP4343," a new neurosteroid very
efficient antidepressant, and "FKBP52," a protein component of hetero-oligomeric
steroid receptors that we found involved in cerebral function, including in
Alzheimer's disease.
PMID- 29963011
TI - Double Stimulation in the Same Ovarian Cycle (DuoStim) to Maximize the Number of
Oocytes Retrieved From Poor Prognosis Patients: A Multicenter Experience and SWOT
Analysis.
AB - A panel of experts known as the POSEIDON group has recently redefined the
spectrum of poor responder patients and introduced the concept of suboptimal
response. Since an ideal management for these patients is still missing, they
highlighted the importance of tailoring the ovarian stimulation based on the
chance of each woman to obtain an euploid blastocyst. Interestingly, a novel
pattern of follicle recruitment has been defined: multiple waves may arise during
a single ovarian cycle. This evidence opened important clinical implications for
the treatment of poor responders. For instance, double stimulation in the
follicular (FPS) and luteal phase (LPS) of the same ovarian cycle (DuoStim) is an
intriguing option to perform two oocyte retrievals in the shortest possible time.
Here, we reported our 2-year experience of DuoStim application in four private
IVF centers. To date, 310 poor prognosis patients completed a DuoStim protocol
and underwent IVF with blastocyst-stage preimplantation-genetic-testing. LPS
resulted into a higher mean number of oocytes collected than FPS; however, their
competence (i.e., fertilization, blastocyst, euploidy rates, and clinical
outcomes after euploid single-embryo-transfer) was comparable. Importantly, the
rate of patients obtaining at least one euploid blastocyst increased from 42.3%
(n = 131/310) after FPS to 65.5% (n = 203/310) with the contribution of LPS. A
summary of the putative advantages and disadvantages of DuoStim was reported here
through a Strengths-Weaknesses-Opportunities-Threats analysis. The strengths of
this approach make it very promising. However, more studies are needed in the
future to limit its weaknesses, shed light on its putative threats, and realize
its opportunities.
PMID- 29963012
TI - Temozolomide and Pituitary Tumors: Current Understanding, Unresolved Issues, and
Future Directions.
AB - Temozolomide, an alkylating agent, initially used in the treatment of gliomas was
expanded to include pituitary tumors in 2006. After 12 years of use, temozolomide
has shown a notable advancement in pituitary tumor treatment with a remarkable
improvement rate in the 5-year overall survival and 5-year progression-free
survival in both aggressive pituitary adenomas and pituitary carcinomas. In this
paper, we review the mechanism of action of temozolomide as alkylating agent, its
interaction with deoxyribonucleic acid repair systems, therapeutic effects in
pituitary tumors, unresolved issues, and future directions relating to new
possibilities of targeted therapy.
PMID- 29963013
TI - A New Role for Estrogen Receptor alpha in Cell Proliferation and Cancer:
Activating the Anticipatory Unfolded Protein Response.
AB - Cells react to a variety of stresses, including accumulation of unfolded or
misfolded protein, by activating the endoplasmic reticulum (EnR) stress sensor,
the unfolded protein response (UPR). The UPR is highly conserved and plays a key
role in the maintenance of protein folding quality control and homeostasis. In
contrast to the classical reactive mode of UPR activation, recent studies
describe a hormone-activated anticipatory UPR. In this pathway, mitogenic
hormones, such as estrogen (E2), epidermal growth factor, and vascular
endothelial growth factor rapidly activate the UPR in anticipation of a future
need for increased protein folding capacity upon cell proliferation. Here, we
focus on this recently unveiled pathway of E2-estrogen receptor alpha (ERalpha)
action. Notably, rapid activation of the anticipatory UPR pathway is essential
for subsequent activation of the E2-ERalpha regulated transcription program.
Moreover, activation of the UPR at diagnosis is a powerful prognostic marker in
ERalpha positive breast cancer. Furthermore, in cells containing ERalpha
mutations that confer estrogen independence and are common in metastatic breast
cancer, the UPR is constitutively activated and linked to antiestrogen
resistance. Lethal ERalpha-dependent hyperactivation of the anticipatory UPR
represents a promising therapeutic approach exploited by a new class of small
molecule ERalpha biomodulator.
PMID- 29963014
TI - In Silico Approaches Applied to the Study of Peptide Analogs of Ile-Pro-Ile in
Relation to Their Dipeptidyl Peptidase IV Inhibitory Properties.
AB - Inhibition of dipeptidyl peptidase IV (DPP-IV) may be exploited to maintain the
incretin effect during the postprandial phase. As a result, glycemic regulation
and energy homeostasis may be improved. Food protein-derived peptides have been
identified as natural agents capable of inhibiting DPP-IV. Ile-Pro-Ile is the
most potent DPP-IV inhibitory peptide identified to date. A minimum analog
peptide set approach was used to study peptide analogs of Ile-Pro-Ile. The DPP-IV
half maximal inhibitory concentration (IC50) values of the 25 peptides evaluated
ranged from 3.9 +/- 1.0 uM (Ile-Pro-Ile) to 247.0 +/- 32.7 uM (Phe-Pro-Phe). The
presence of Pro at position 2 of tripeptides was required to achieve high DPP-IV
inhibition. Most peptides behaved as competitive inhibitors of DPP-IV with the
exception of peptides with a N-terminal Trp, which were mixed-type inhibitors.
While possessing the structure of preferred DPP-IV substrates, most peptides
studied were particularly stable during 30 min incubation with DPP-IV. Molecular
docking revealed that Ile-Pro-Ile and its peptide analogs interacted in a very
similar manner with the active site of DPP-IV. In addition, no correlation was
found between the Hydropathic INTeraction score and the DPP-IV IC50 values of the
peptides studied. This outcome suggests that free energy may not be directly
responsible for enzyme inhibition by the peptides. Finally, novel DPP-IV
inhibitory peptides were identified using the strategy employed herein. These
results may be relevant for the development of food protein-derived peptides with
serum glucose lowering and food intake regulatory properties in humans.
PMID- 29963016
TI - Transcriptomic, Proteomic, and Bioelectrochemical Characterization of an
Exoelectrogen Geobacter soli Grown With Different Electron Acceptors.
AB - The ability of Geobacter species to transfer electrons outside cells enables them
to play an important role in biogeochemical and bioenergy processes. Our
knowledge of the extracellular electron transfer (EET) process in the genus
Geobacter is mainly from the study of G. sulfurreducens, and in order to fully
investigate the EET mechanisms in the genus Geobacter, other Geobacter species
should also be considered. This study focused on the EET of Geobacter soli GSS01,
which exhibited a capability of reducing insoluble Fe(III) oxides and generating
electrical current comparable with G. sulfurreducens PCA. Electrochemical
characterization, including cyclic voltammetry, differential pulse voltammetry,
and electrochemical in situ FTIR spectra, revealed that different redox proteins
contributed to the electrochemical behaviors of G. soli and G. sulfurreducens.
Based on comparative transcriptomic and proteomic analyses, OmcS was the most
upregulated protein in both G. soli and G. sulfurreducens cells grown with
insoluble Fe(III) oxides vs. soluble electron acceptor. However, the proteins
including OmcE and PilA that were previously reported as being important for EET
in G. sulfurreducens were downregulated or unchanged in G. soli cells grown with
insoluble electron acceptors vs. soluble electron acceptor, and many proteins
that were upregulated in G. soli cells grown with insoluble electron acceptors
vs. soluble electron acceptor, such as OmcN, are not important for EET in G.
sulfurreducens. We also identified 30 differentially expressed small RNAs (sRNAs)
in G. soli cells grown with different acceptors. Taken together, these findings
help to understand the versatile EET mechanisms that exist in the genus Geobacter
and point to the possibility of sRNA in modulating EET gene expression.
PMID- 29963015
TI - Role of Hormonal Circuitry Upon T Cell Development in Chagas Disease: Possible
Implications on T Cell Dysfunctions.
AB - T cell response plays an essential role in the host resistance to infection by
the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease.
This infection is often associated with multiple manifestations of T cell
dysfunction, both during the acute and the chronic phases of disease.
Additionally, the normal development of T cells is affected. As seen in animal
models of Chagas disease, there is a strong thymic atrophy due to massive death
of CD4+CD8+ double-positive cells by apoptosis and an abnormal escape of immature
and potentially autoreactive thymocytes from the organ. Furthermore, an increase
in the release of corticosterone triggered by T. cruzi-driven systemic
inflammation is strongly associated with the alterations seen in the thymus of
infected animals. Moreover, changes in the levels of other hormones, including
growth hormone, prolactin, and testosterone are also able to contribute to the
disruption of thymic homeostasis secondary to T. cruzi infection. In this review,
we discuss the role of hormonal circuits involved in the normal T cell
development and trafficking, as well as their role on the thymic alterations
likely related to the peripheral T cell disturbances largely reported in both
chagasic patients and animal models of Chagas disease.
PMID- 29963017
TI - Oral Delivery of Nisin in Resistant Starch Based Matrices Alters the Gut
Microbiota in Mice.
AB - There is a growing recognition of the role the gastrointestinal microbiota plays
in health and disease. Ingested antimicrobial proteins and peptides have the
potential to alter the gastrointestinal microbiota; particularly if protected
from digestion. Nisin is an antimicrobial peptide that is used as a food
preservative. This study examined the ability of nisin to affect the murine
microbiota when fed to mice in two different starch based matrices; a starch
dough comprising raw starch granules and a starch gel comprising starch that was
gelatinized and retrograded. The effects of the two starch matrices by themselves
on the microbiota were also examined. Following 16S rRNA compositional
sequencing, beta diversity analysis highlighted a significant difference (p =
0.001, n = 10) in the murine microbiota between the four diet groups. The
differences between the two nisin containing diets were mainly attributable to
differences in the nisin release from the starch matrices while the differences
between the carriers were mainly attributable to the type of resistant starch
they possessed. Indeed, the differences in the relative abundance of several
genera in the mice consuming the starch dough and starch gel diets, in particular
Akkermansia, the relative abundance of which was 0.5 and 11.9%, respectively (p =
0.0002, n = 10), points to the potential value of resistance starch as a
modulator of beneficial gut microbes. Intact nisin and nisin digestion products
(in particular nisin fragment 22-31) were detected in the feces and the nisin was
biologically active. However, despite a three-fold greater consumption of nisin
in the group fed the nisin in starch dough diet, twice as much nisin was detected
in the feces of the group which consumed the nisin in starch gel diet. In
addition, the relative abundance of three times as many genera from the lower
gastrointestinal tract (GIT) were significantly different (p < 0.001, n = 10) to
the control for the group fed the nisin in starch gel diet, implying that the
starch gel afforded a degree of protection from digestion to the nisin entrapped
within it.
PMID- 29963019
TI - An Antimicrobial Peptide Induces FIG1-Dependent Cell Death During Cell Cycle
Arrest in Yeast.
AB - Although most antibiotics act on cells that are actively dividing and non
dividing cells such as in microbe sporulation or cancer stem cells represent a
new paradigm for the control of disease. In addition to their relevance to
health, such antibiotics may promote our understanding of the relationship
between the cell cycle and cell death. No antibiotic specifically acting on
microbial cells arrested in their cell cycle has been identified until the
present time. In this study we used an antimicrobial peptide derived from alpha
pheromone, IP-1, targeted against MATa Saccharomyces cerevisiae cells in order to
assess its dependence on cell cycle arrest to kill cells. Analysis by flow
cytometry and fluorescence microscopy of various null mutations of genes involved
in biological processes activated by the pheromone pathway (the mitogen-activated
protein kinase pathway, cell cycle arrest, cell proliferation, autophagy, calcium
influx) showed that IP-1 requires arrest in G0/G1 in order to kill yeast cells.
Isolating cells in different cell cycle phases by elutriation provided further
evidence that entry into cell cycle arrest, and not into G1 phase, is necessary
if our peptide is to kill yeast cells. We also describe a variant of IP-1 that
does not activate the pheromone pathway and consequently does not kill yeast
cells that express the pheromone's receptor; the use of this variant peptide in
combination with different cell cycle inhibitors that induce cell cycle arrest
independently of the pheromone pathway confirmed that it is cell cycle arrest
that is required for the cell death induced by this peptide in yeast. We show
that the cell death induced by IP-1 differs from that induced by alpha-pheromone
and depends on FIG1 in a way independent of the cell cycle arrest induced by the
pheromone. Thus, IP-1 is the first molecule described that specifically kills
microbial cells during cell cycle arrest, a subject of interest beyond the
process of mating in yeast cells. The experimental system described in this study
should be useful in the study of the mechanisms at play in the communication
between cell cycle arrest and cell death on other organisms, hence promoting the
development of new antibiotics.
PMID- 29963018
TI - Relationships Between Gastrointestinal Parasite Infections and the Fecal
Microbiome in Free-Ranging Western Lowland Gorillas.
AB - Relationships between gastrointestinal parasites (GIPs) and the gastrointestinal
microbiome (GIM) are widely discussed topics across mammalian species due to
their possible impact on the host's health. GIPs may change the environment
determining alterations in GIM composition. We evaluated the associations between
GIP infections and fecal microbiome composition in two habituated and two
unhabituated groups of wild western lowland gorillas (Gorilla g. gorilla) from
Dzanga Sangha Protected Areas, Central African Republic. We examined 43 fecal
samples for GIPs and quantified strongylid nematodes. We characterized fecal
microbiome composition through 454 pyrosequencing of the V1-V3 region of the
bacterial 16S rRNA gene. Entamoeba spp. infections were associated with
significant differences in abundances of bacterial taxa that likely play
important roles in nutrition and metabolism for the host, besides being
characteristic members of the gorilla gut microbiome. We did not observe any
relationships between relative abundances of several bacterial taxa and
strongylid egg counts. Based on our findings, we suggest that there is a
significant relationship between fecal microbiome and Entamoeba infection in wild
gorillas. This study contributes to the overall knowledge about factors involved
in modulating GIM communities in great apes.
PMID- 29963020
TI - Herring Oil and Omega Fatty Acids Inhibit Staphylococcus aureus Biofilm Formation
and Virulence.
AB - Staphylococcus aureus is notorious for its ability to become resistant to
antibiotics and biofilms play a critical role in antibiotic tolerance. S. aureus
is also capable of secreting several exotoxins associated with the pathogenesis
of sepsis and pneumonia. Thus, the objectives of the study were to examine S.
aureus biofilm formation in vitro, and the effects of herring oil and its main
components, omega fatty acids [cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) and
cis-5,8,11,14,17-eicosapentaenoic acid (EPA)], on virulence factor production and
transcriptional changes in S. aureus. Herring oil decreased biofilm formation by
two S. aureus strains. GC-MS analysis revealed the presence of several
polyunsaturated fatty acids in herring oil, and of these, two omega-3 fatty
acids, DHA and EPA, significantly inhibited S. aureus biofilm formation. In
addition, herring oil, DHA, and EPA at 20 MUg/ml significantly decreased the
hemolytic effect of S. aureus on human red blood cells, and when pre-treated to
S. aureus, the bacterium was more easily killed by human whole blood.
Transcriptional analysis showed that herring oil, DHA, and EPA repressed the
expression of the alpha-hemolysin hla gene. Furthermore, in a Caenorhabditis
elegans nematode model, all three prolonged nematode survival in the presence of
S. aureus. These findings suggest that herring oil, DHA, and EPA are potentially
useful for controlling persistent S. aureus infection.
PMID- 29963021
TI - Gut Bacterial Communities of Dendroctonus valens and Monoterpenes and
Carbohydrates of Pinus tabuliformis at Different Attack Densities to Host Pines.
AB - Insects harbor a community of gut bacteria, ranging from pathogenic to obligate
mutualistic organisms. Both biotic and abiotic factors can influence species
composition and structure of the insect gut bacterial communities. Dendroctonus
valens is a destructive forest pest in China. To overcome host pine defenses,
beetles mass-attack the pine to a threshold density that can exhaust pine
defenses. The intensity of pine chemical defenses and carbohydrate concentrations
of pines can be influenced by beetle attack, both of which are known factors that
modify beetle's gut microbiota. However, little is known to what extent variation
exists in the beetle's gut communities, and host monoterpenes and carbohydrates
at different attack densities. In this study, the gut bacterial microbiota of D.
valens at low and high attack densities were analyzed, and monoterpenes and
carbohydrates in host pine phloem were assayed in parallel. The results showed
that no significant changes of gut bacterial communities of the beetles and
concentrations of D-glucose, D-pinitol, and D-fructose in pine phloem were found
between low and high attack densities. The concentrations of alpha-pinene, beta
pinene, limonene at high attack densities were significantly higher than those at
low attack densities. Our results suggested that different attack densities of D.
valens influence monoterpenes concentration of host pines' phloem but have no
significant impact on gut bacterial community structures of D. valens and
carbohydrate concentration of host trees' phloem in early attack phase. Similar
gut bacterial community structures of D. valens between low and high attack
densities might be due to the quick adaptation of gut microbiota to high
monoterpenes concentrations.
PMID- 29963022
TI - Experimental Microbial Alteration and Fe Mobilization From Basaltic Rocks of the
ICDP HSDP2 Drill Core, Hilo, Hawaii.
AB - The interaction of a single bacterial species (Burkholderia fungorum) with
basaltic rocks from the ICDP HSDP2 drill core and synthetic basaltic glasses was
investigated in batch laboratory experiments to better understand the role of
microbial activity on rock alteration and Fe mobilization. Incubation experiments
were performed with drill core basaltic rock samples to investigate differences
in the solution chemistry during biotic and abiotic alteration. Additionally,
colonization experiments with synthetic basaltic glasses of different Fe redox
states and residual stresses were performed to evaluate their influence on
microbial activity and surface attachment of cells. In biotic incubation
experiments bacterial growth was observed and the release of Fe and other major
elements from drill core basaltic rocks to solution exceeded that of abiotic
controls only when the rock sample assay was nutrient depleted. The concentration
of dissolved major elements in solution in biotic colonization experiments with
synthetic basaltic glasses increased with increasing residual stress and Fe(II)
content. Furthermore, the concentration of dissolved Fe and Al increased
similarly in biotic colonization experiments indicating that their dissolution
might be triggered by microbial activity. Surface morphology imaging by SEM
revealed that cells on basaltic rocks in incubation experiments were most
abundant on the glass and surfaces with high roughness and almost absent on
minerals. In colonization experiments, basaltic glasses with residual stress and
high Fe(II) content were intensely covered with a cellular biofilm. In contrast,
glasses with high Fe(III) content and no residual stress were sparsely colonized.
We therefore conclude that structurally bound Fe is most probably used by B.
fungorum as a nutrient. Furthermore, we assume that microbial activity overall
increased rock dissolution as soon as the environment becomes nutrient depleted.
Our results show that besides compositional effects, other factors such as redox
state and residual stress can control microbial alteration of basaltic glasses.
PMID- 29963023
TI - Differentiation-Dependent Regulation of Human Endogenous Retrovirus K Sequences
and Neighboring Genes in Germ Cell Tumor Cells.
AB - Under physiological conditions, most human endogenous retroviruses (HERVs) are
transcriptionally silent. However, re-activation of HERVs is observed under
pathological conditions like inflammation or cancer. In addition to expression of
HERV sequences, an impact of HERV-loci on expression of adjacent genes has been
suggested as probably important patho-physiological mechanism. A candidate for
such a gene is PRODH (proline dehydrogenase 1), which is located on chromosome 22
adjacent to HERVK-24. Germ cell tumors (GCTs) are known to express high level of
HERVK sequences. In addition, non-seminomatous GCT are useful models to study
HERV expression in the context of differentiation since they reflect aspects of
cellular development during embryogenesis and usually contain different cell
types. This is due to the embryonal carcinoma (EC) cells, which are the stem cell
component of GCT. They are pluripotent, show high expression of pluripotency
markers like OCT4 and LIN28A and can differentiate into either somatic
derivatives (teratoma cells) or choriocarcinoma or yolk-sac tumor cells
reflecting extra-embryonal differentiation. OCT4 is lost upon differentiation. We
used GCT derived cell lines of varying differentiation stages to analyze
expression of HERVK and PRODH. Differentiation status and cellular relationship
of GCT cells was determined using microarray analysis and western blotting of the
embryonic pluripotency markers OCT4 and LIN28A. The highest expression of HERVK
was found in undifferentiated EC cells, which retain a stem cell phenotype and
express both OCT4 and LIN28. In contrast, the lowest expression of HERVK was
observed in somatic differentiated GCT cells which also lack OCT4 and LIN28A
whereas GCT cells with differentiation characteristics of yolk-sac tumor
expressed LIN28A but not OCT4 and showed intermediate level of HERVK. A similar
pattern was found for PRODH. Differentiation of EC cells by siRNA mediated knock
down of OCT4 or treatment with differentiation inducing medium decreased
expression of HERVK and PRODH. Treatment of differentiated GCT cells with 5'
azacytidine and trichostatin A increased expression of HERVK and PRODH,
indicating that epigenetic mechanisms are responsible for altered expression of
these genes. Our data suggest that HERVK expression is dependent on cellular
differentiation stages regulated by epigenetic mechanisms, which can also affect
expression of neighboring genes.
PMID- 29963024
TI - Acinetobacter calcoaceticus CSY-P13 Mitigates Stress of Ferulic and p
Hydroxybenzoic Acids in Cucumber by Affecting Antioxidant Enzyme Activity and
Soil Bacterial Community.
AB - Ferulic acid (FA) and p-hydroxybenzoic acid (PHBA) are main phenolic compounds
accumulated in rhizosphere of continuously cropped cucumber, causing stress in
plants. Microbial degradation of a mixture of FA and PHBA is not well understood
in soil. We isolated a strain CSY-P13 of Acinetobacter calcoaceticus, inoculated
it into soil to protect cucumber from FA and PHBA stress, and explored a
mechanism underlying the protection. CSY-P13 effectively degraded a mixture of FA
and PHBA in culture solution under conditions of 39.37 degrees C, pH 6.97, and
21.59 g L-1 potassium dihydrogen phosphate, giving rise to 4-vinyl guaiacol,
vanillin, vanillic acid, and protocatechuic acid. During FA and PHBA degradation,
activities of superoxide dismutase (SOD), catalase, ascorbate peroxidase, and
dehydroascorbate reductase in CSY-P13 were induced. Inoculated into cucumber
planted soil containing 220 MUg g-1 mixture of FA and PHBA, CSY-P13 degraded FA
and PHBA in soil, increased plant height, and decreased malonaldehyde, superoxide
radical, and hydrogen peroxide levels in leaves. CSY-P13 also enhanced SOD,
guaiacol peroxidase, catalase, glutathione peroxidase, ascorbate peroxidase,
monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione
reductase activities; increased ascorbate and glutathione contents; and elevated
transcript levels of copper/zinc SOD, manganese SOD, and catalase in leaves under
FA and PHBA. Moreover, CSY-P13 increased phosphatase, catalase, urease, and
sucrase activities and changed bacterial richness, diversity, and community
composition by high throughput sequencing in cucumber-planted soil supplemented
with the mixture of FA and PHBA. So CSY-P13 degrades the mixture of FA and PHBA
in soil and mitigates stress from the two phenolic compounds in cucumber by
activating antioxidant enzymes, changing soil bacterial community, and inducing
soil enzymes.
PMID- 29963025
TI - Prevalence and Characterization of Staphylococcus aureus Isolated From Retail
Vegetables in China.
AB - Staphylococcus aureus is a pathogen associated with serious community and
hospital-acquired diseases. The aim of this study was to investigate the
prevalence of S. aureus from retail vegetables in China and then characterized S.
aureus isolates by antibiotic resistance, staphylococcal enterotoxin genes, spa
typing and multi-locus sequence typing. Of 419 retail vegetable samples from 39
cities in China during 2011-2016, 24 (5.73%) samples were positive for S. aureus
and the geometric mean was 3.85 MPN/g. The prevalence of S. aureus was highest in
lettuce (13/84, 15.48%) followed by tomato (7/110, 6.36%), caraway (2/87, 2.30%),
and cucumber (2/128, 1.56%), whereas other vegetables were free of S. aureus. A
total of 30 isolates were analyzed. For antibiotics susceptibility test, most
isolates (93.3%) were resistant to ampicillin and penicillin, whereas all
isolates were susceptible to linezolid, trimethoprim/sulphamethoxazole 1:19,
nitrofurantoin, rifampicin, and teicoplanin. All isolates (30/30, 100%) were
resistant or intermediate resistant to more than three tested antibiotics,
including 9 isolates (30%) were resisted more than 10 antibiotics. Five isolates
were resistant to cefoxitin and carried mecA genes which confirmed as MRSA. Of
the 18 investigated SE genes, the sem gene was the most frequently detected
(86.7%) followed by the sec (83.3%), sep (70.0%), seg (56.7%), sel (53.3%), seh
(50.0%), seq (50.0%), sej (46.7%), seb (36.7%), sen (36.7%), and ser (33.3%)
genes were harbored by more than one third of the isolates, whereas the seo and
seu were detected in only 6.75% of the isolates. MLST and spa typing observed
high genetic diversity in S. aureus isolated from retail vegetable in China. ST59
t437 was the predominant types (3/5, 60%) of MRSA isolates, whereas ST188-t189
was the predominant types (7/25, 28%) of MSSA isolates. Our study reflects that
the retail vegetable in China could be contaminated with S. aureus but the levels
of S. aureus were not very excessive. In addition, these isolates had virulence
potential, most of them were enterotoxigenic and multiple antimicrobial
resistance, should be draw public attention. These data have signification
implications for epidemiological and public health studies of this pathogen.
PMID- 29963026
TI - Multispecies and Clonal Dissemination of OXA-48 Carbapenemase in
Enterobacteriaceae From Companion Animals in Germany, 2009-2016.
AB - The increasing spread of carbapenemase-producing Enterobacteriaceae (CPE) poses a
serious threat to public health. Recent studies suggested animals as a putative
source of such bacteria. We investigated 19,025 Escherichia coli, 1607 Klebsiella
spp. and 570 Enterobacter spp. isolated from livestock, companion animal, horse,
and pet samples between 2009 and 2016 in our routine diagnostic laboratory for
reduced susceptibility to carbapenems (CP) by using meropenem-containing media.
Actively screened CP non-susceptible strains as well as 367 archived ESBL/AmpC
beta-lactamase-producing Enterobacteriaceae were then tested for the presence of
CP genes by PCRs. Among 21,569 isolates, OXA-48 could be identified as the sole
carbapenemase type in 137 (0.64%) strains. The blaOXA-48 gene was located on an
~60-kb IncL plasmid and sequence analysis revealed high similarity to reference
plasmid pOXA-48a, which has been involved in the global spread of the blaOXA-48
gene in humans for many years. Klebsiella pneumoniae was the predominant OXA-48
producer (n = 86; 6.6% of all K. pneumoniae isolates), followed by E. cloacae (n
= 28; 5.0%), Klebsiella oxytoca (n = 1; 0.3%), and E. coli (n = 22, 0.1%). OXA-48
was not found in livestock, but in dogs (120/3182; 3.8%), cats (13/792; 1.6%),
guinea pig (1/43; 2.3%), rat (1/23; 4.3%), mouse (1/180; 0.6%), and one rabbit
(1/144; 0.7%). Genotyping identified few major clones among the different
enterobacteria species, including sequence types ST11 and ST15 for K. pneumoniae,
ST1196 for E. coli, and ST506 and ST78 for E. cloacae, most of which were
previously involved in the dissemination of multidrug-resistant strains in
humans. The majority of OXA-48 isolates (n = 112) originated from a university
veterinary clinic (UVC), while animals from further 16 veterinary institutions
were positive. Clonal analyses suggested nosocomial events related to different
species and STs in two veterinary clinics and horizontal transfer of the pOXA-48
like plasmid between bacterial species and animals. A systematic monitoring is
urgently needed to assess the dissemination of CPE not only in livestock but also
in companion animals and veterinary clinics.
PMID- 29963027
TI - Genome Sequencing of Streptomyces atratus SCSIOZH16 and Activation Production of
Nocardamine via Metabolic Engineering.
AB - The Actinomycetes are metabolically flexible microorganisms capable of producing
a wide range of interesting compounds, including but by no means limited to,
siderophores which have high affinity for ferric iron. In this study, we report
the complete genome sequence of marine-derived Streptomyces atratus ZH16 and the
activation of an embedded siderophore gene cluster via the application of
metabolic engineering methods. The S. atratus ZH16 genome reveals that this
strain has the potential to produce 26 categories of natural products (NPs)
barring the ilamycins. Our activation studies revealed S. atratus SCSIO ZH16 to
be a promising source of the production of nocardamine-type (desferrioxamine)
compounds which are important in treating acute iron intoxication and performing
ecological remediation. We conclude that metabolic engineering provides a highly
effective strategy by which to discover drug-like compounds and new NPs in the
genomic era.
PMID- 29963028
TI - Comparative Genomic and Phenotypic Analysis of the Vaginal Probiotic
Lactobacillus rhamnosus GR-1.
AB - Lactobacillus represents a versatile bacterial genus, which can adapt to a wide
variety of ecological niches, including human body sites such as the intestinal
and urogenital tract. In this study, the complete genome sequence of the vaginal
probiotic Lactobacillus rhamnosus GR-1 was determined and compared to other L.
rhamnosus strains at genomic and phenotypic level. The strain GR-1 was originally
isolated from a female urethra, and was assessed with L. rhamnosus GG from a
feces sample of a healthy male, and L. rhamnosus LC705 from a dairy product. A
key difference is the absence in GR-1 and LC705 of the spaCBA locus required for
pili-mediated intestinal epithelial adhesion. In addition, the L. rhamnosus GR-1
genome contains a unique cluster for exopolysaccharide production, which is
postulated to synthesize glucose-rich, rhamnose-lacking exopolysaccharide
molecules that are different from the galactose-rich extracellular polysaccharide
of L. rhamnosus GG. Compared to L. rhamnosus GG, L. rhamnosus GR-1 was also
genetically predicted and experimentally shown to better metabolize lactose and
maltose, and to better withstand oxidative stress, which is of relevance in the
vagina. This study could thus provide a molecular framework for the selection of
the optimal probiotic strain for each targeted niche and condition, but further
substantiation of niche adaptation mechanisms of lactobacilli is warranted.
PMID- 29963029
TI - Microbial Community Structure-Function Relationships in Yaquina Bay Estuary
Reveal Spatially Distinct Carbon and Nitrogen Cycling Capacities.
AB - Linking microbial community structure to ecological processes requires
understanding of the functional roles among individual populations and the
factors that influence their distributions. These structure-function
relationships are particularly difficult to disentangle in estuaries, due to
highly variable physico-chemical conditions. Yet, examining microbe-mediated
turnover of resources in these "bioreactor" ecosystems is critical for
understanding estuarine ecology. In this study, a combined metagenomics and
metaproteomics approach was used to show that the unequal distribution of
microbial populations across the Yaquina Bay estuary led to a habitat-specific
taxonomic and functional structure and a clear spatial distribution in microbe
mediated capacities for cycling of carbon and nitrogen. For example, size
fractionation revealed that communities inhabiting suspended particulate material
encoded more diverse types of metabolisms (e.g., fermentation and
denitrification) than those with a planktonic lifestyle, suggesting that the
metabolic reactions can differ between size fractions of the same parcel of an
estuarine water column. Similarly, communities inhabiting oligotrophic conditions
in the lower estuary were enriched in genes involved in central carbon metabolism
(e.g., TCA cycle), while communities in the upper estuary were enriched in genes
typical of copiotrophic populations (e.g., cell growth, cell division).
Integrating gene and protein data revealed that abundant populations of
Flavobacteriales and Rhodobacterales encoded similar genomic functions, yet
differed significantly in protein expression, dedicating a large proportion of
their respective proteomes to rapid growth and division versus metabolic
versatility and resource acquisition. This suggested potentially distinct life
strategies between these two co-occurring lineages and was concomitant with
differing patterns of positive evolutionary selection on their encoded genes.
Microbial communities and their functions across Yaquina Bay appear to be
structured by population-level habitat preferences, resulting in spatially
distinct elemental cycling, while within each community, forces such as
competitive exclusion and evolutionary selection influence species life
strategies and may help maintain microbial diversity.
PMID- 29963030
TI - cpubi4 Is Essential for Development and Virulence in Chestnut Blight Fungus.
AB - Ubiquitination plays key roles in eukaryotic growth, stress adaptation, and
metabolic regulation. In our previous work, ubiquitin was found to be secreted in
the hypovirus-infected strain of Cryphonectria parasitica, a phytopathogenic
filamentous fungus responsible for the chestnut blight. Here we report the
functional and molecular characterization of a polyubiquitin gene, cpubi4, in C.
parasitica. The expression of cpubi4 was upregulated by the infection of a
hypovirus. Deletion of cpubi4 resulted in abnormal morphology, reduced
sporulation, attenuation of virulence, and significant reduction in
ubiquitination. A total of 378 sites in 236 proteins were identified to be
significantly decreased in ubiquitination in the absence of cpubi4. Quantitative
proteome analysis revealed that 285 in 4,776 identified proteins changed in
abundance (1.5-fold, P < 0.05) in the cpubi4 null mutant, as compared with the
wild-type strain.
PMID- 29963031
TI - Changes in Polyphenolic Concentrations of Table Olives (cv. Itrana) Produced
Under Different Irrigation Regimes During Spontaneous or Inoculated Fermentation.
AB - Irrigation is widely used for the production of table olives because it increases
fruit size and yield. However, irrigation also determines less accumulation of
total phenols, an increase in water content, a decrease of firmness, lower
concentrations of soluble sugars in the mesocarp, thus positively or negatively
affecting the fermentation process for the production of table olives. In this
study we tested the hypothesis that green fruits of cultivar Itrana obtained by
different irrigation regimes had different phenolic concentration that responded
differentially to spontaneous or inoculated fermentation. Fruits were harvested
from two orchards in the Latina province of Latium, Italy, which had been
irrigated with different volumes of water during the growing season to compare
the evolution of spontaneous and inoculated fermentation processes. We measured
fruit characteristics at harvest, changes in the concentrations of secoiridoids
and lignans, and main microbial groups abundance during fermentation. At harvest
and during fermentation the concentration of phenolic compounds was higher in
fruits sampled from trees that had received less water in the field. Differences
were observed between spontaneous and inoculated fermentations, with a prevalence
of lactic acid bacteria (LAB) in inoculated samples. In particular, oleuropein
concentration completely disappeared only from samples inoculated with the two
selected strains used as starters. The inoculum with selected LAB positively
influenced the fermentation process of green olives, whereas the irrigation
regime previously experienced by trees did not alter fermentation.
PMID- 29963032
TI - Synchrony of Eukaryotic and Prokaryotic Planktonic Communities in Three
Seasonally Sampled Austrian Lakes.
AB - Freshwater systems are characterized by an enormous diversity of eukaryotic
protists and prokaryotic taxa. The community structures in different lakes are
thereby influenced by factors such as habitat size, lake chemistry, biotic
interactions, and seasonality. In our study, we used high throughput 454
sequencing to study the diversity and temporal changes of prokaryotic and
eukaryotic planktonic communities in three Austrian lakes during the ice-free
season. In the following year, one lake was sampled again with a reduced set of
sampling dates to observe reoccurring patterns. Cluster analyses (based on SSU V9
(eukaryotic) and V4 (prokaryotic) OTU composition) grouped samples according to
their origin followed by separation into seasonal clusters, indicating that each
lake has a unique signature based on OTU composition. These results suggest a
strong habitat-specificity of microbial communities and in particular of
community patterns at the OTU level. A comparison of the prokaryotic and
eukaryotic datasets via co-inertia analysis (CIA) showed a consistent clustering
of prokaryotic and eukaryotic samples, probably reacting to the same
environmental forces (e.g., pH, conductivity). In addition, the shifts in
eukaryotic and bacterioplanktonic communities generally occurred at the same time
and on the same scale. Regression analyses revealed a linear relationship between
an increase in Bray-Curtis dissimilarities and elapsed time. Our study shows a
pronounced coupling between bacteria and eukaryotes in seasonal samplings of the
three analyzed lakes. However, our temporal resolution (biweekly sampling) and
data on abiotic factors were insufficient to determine if this was caused by
direct biotic interactions or by reacting to the same seasonally changing
environmental forces.
PMID- 29963033
TI - Crop Rotation and Straw Application Impact Microbial Communities in Italian and
Philippine Soils and the Rhizosphere of Zea mays.
AB - Rice is one of the most important nourishments and its cultivation binds large
agricultural areas in the world. Its cultivation leads to huge water consumption
and high methane emissions. To diminish these problems, crop rotation between
paddy rice and maize is introduced in Asia, but can lead to losses of carbon and
water by the formation of desiccation cracks. To counteract these problems rice
straw can be applied. We analyzed soil microbial responses to different crop
rotation systems [rice-rice (RR), maize-maize (MM), maize-rice (MR)] and to rice
straw application in the soil and rhizosphere of maize. Zea mays was grown in
microcosms using soils from different field locations, each including different
crop rotation regimes. The bacterial and fungal community composition was
analyzed by 16S rRNA gene and ITS based amplicon sequencing in the bulk soil and
rhizosphere. The microbiota was clearly different in soils from the different
field locations (analysis of similarity, ANOSIM: R = 0.516 for the bacterial
community; R = 0.817 for the fungal community). Within the field locations, crop
rotation contributed differently to the variation in microbial community
composition. Strong differences were observed in communities inhabiting soils
under monosuccession (RR vs. MM) (ANOSIM: R = 0.923 for the bacterial and R =
0.714 for the fungal community), while the communities in soils undergoing MR
crop rotation were more similar to those of the corresponding RR soils (ANOSIM: R
= 0.111-0.175). The observed differences could be explained by altered oxygen
availabilities in RR and MR soils, resulting in an enrichment of anaerobic
bacteria in the soils, and the presence of the different crops, leading to the
enrichment of host-plant specific microbial communities. The responses of the
microbial communities to the application of rice straw in the microcosms were
rather weak compared to the other factors. The taxa responding in bulk soil and
rhizosphere were mostly distinct. In conclusion, this study revealed that the
different agricultural management practices affect microbial community
composition to different extent, not only in the bulk soil but also in the
rhizosphere, and that the microbial responses in bulk soil and rhizosphere are
distinct.
PMID- 29963034
TI - Trehalose Contributes to Gamma-Linolenic Acid Accumulation in Cunninghamella
echinulata Based on de Novo Transcriptomic and Lipidomic Analyses.
AB - Gamma-linolenic acid (GLA) is essential for the well-being of humans and other
animals. People may lack GLA because of aging or diseases, and thus, dietary
supplements or medical reagents containing GLA-enriched lipids are in demand.
Cunninghamella echinulata is a potential GLA-producing strain. Interestingly, we
found that the GLA content of C. echinulata FR3 was up to 21% (proportion of
total lipids) when trehalose was used as a carbon source, significantly higher
than the 13% found when glucose was used. Trehalose is quite common and can be
accumulated in microorganisms under stress conditions. However, little
information is available regarding the role of trehalose in GLA synthesis and
accumulation. Our study aimed to understand how the metabolism of C. echinulata
responds to trehalose as a carbon source for GLA and lipid biosynthesis. We
profiled the major sugars, fatty acids, phospholipids, and gene transcripts of C.
echinulata FR3 grown in trehalose medium with glucose as a control by de novo
transcriptomics, lipidomics, and other methods. The results showed that trehalose
could influence the expression of desaturases and that the GLA proportion
increased because of delta-6 desaturase upregulation. The increased GLA was
transferred to the extracellular environment through the active PI ion channel,
which prefers polyunsaturated acyl chains. At the same time, trehalose might
prevent GLA from peroxidation by forming a trehalose-polyunsaturated fatty acid
(PUFA) complex. Our study provides new insights into the functions of trehalose
in GLA accumulation.
PMID- 29963036
TI - A Bcl-2 Associated Athanogene (bagA) Modulates Sexual Development and Secondary
Metabolism in the Filamentous Fungus Aspergillus nidulans.
AB - The Bcl-2 associated athanogene (Bag) family is a multifunctional group of
proteins distinguished by a conserved region known as the Bag domain (BD).
Herein, we discuss the discovery and characterization of a Bag protein in the
model genetic fungus Aspergillus nidulans, we designated BagA. BagA shares
striking similarities in 3D structure, domain organization, amino acid
properties, and Hsp70 binding surfaces to animal and plant Bags. While Hsp70
binding is a common feature of Bag proteins, our experimental evidence shows that
BagA does not cooperate with A. nidulans Hsp70s, suggesting this association may
not be a universal feature of Bag proteins. Gene expression of bagA was strongly
induced during sexual development suggesting a role in developmental processes.
Accordingly, the deletion of bagA (DeltabagA) negatively impacted sexual
development, while its overexpression resulted in constitutive induction of
sexual fruiting bodies and spores. Asexual and sexual development was linked to
secondary metabolism in A. nidulans. Our data show that the deletion of bagA also
provoked an altered secondary metabolite (SM) profile in both sexual and
vegetative growth phases. Indeed, LC-MS analysis showed a significant enrichment
of SMs in DeltabagA, including novel metabolites not produced by wild type
strain. Enrichment of SMs in DeltabagA strain is particularly intriguing and
suggest that altering cellular homeostasis can be used as a provocative strategy
to activate cryptic metabolites and uncover novel bioactive compounds. Overall,
our results indicate that Bag proteins in filamentous fungi share developmental
regulatory roles with their animal and plant counterparts. We also show a
potentially unique role for BagA in modulating secondary metabolism in A.
nidulans. To our knowledge, this study provides a first insight into Bag function
in filamentous fungi.
PMID- 29963037
TI - On the Origin and Evolutionary Relationships of the Reverse Transcriptases
Associated With Type III CRISPR-Cas Systems.
AB - Reverse transcriptases (RTs) closely related to those encoded by group II introns
but lacking the intron RNA structure have been found associated with type III
clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems, a
prokaryotic immune system against invading viruses and foreign genetic elements.
Two models have been proposed to explain the origin and evolutionary
relationships of these RTs: (i) the "single point of origin" model, according to
which these RTs originated from a single acquisition event in bacterial, with the
various protein domains (RT, RT-Cas1, and Cas6-RT-Cas1 fusions) corresponding to
single points in evolution; and (ii) the "various origins" model, according to
which, independent acquisition events in different evolutionary episodes led to
these fusions. We tested these alternative hypotheses, by analyzing and
integrating published datasets of RT sequences associated with CRISPR-Cas systems
and inferring phylogenetic trees by maximum likelihood (ML) methods. The RTs
studied could be grouped into 13 clades, mostly in bacteria, in which they
probably evolved. The various clades appear to form three independent lineages in
bacteria and a recent lineage in archaea. Our data show that the Cas6 domain was
acquired twice, independently, through RT-Cas1 fusion, in the bacterial lineages.
Taken together, there more evidence to support the "various origins" hypothesis.
PMID- 29963035
TI - Identification of a Novel Polyamine Scaffold With Potent Efflux Pump Inhibition
Activity Toward Multi-Drug Resistant Bacterial Pathogens.
AB - We have previously reported the use of combinatorial chemistry to identify broad
spectrum antibacterial agents. Herein, we extend our analysis of this technology
toward the discovery of anti-resistance molecules, focusing on efflux pump
inhibitors. Using high-throughput screening against multi-drug resistant
Pseudomonas aeruginosa, we identified a polyamine scaffold that demonstrated
strong efflux pump inhibition without possessing antibacterial effects. We
determined that these molecules were most effective with an amine functionality
at R1 and benzene functionalities at R2 and R3. From a library of 188 compounds,
we studied the properties of 5 lead agents in detail, observing a fivefold to
eightfold decrease in the 90% effective concentration of tetracycline,
chloramphenicol, and aztreonam toward P. aeruginosa isolates. Additionally, we
determined that our molecules were not only active toward P. aeruginosa, but
toward Acinetobacter baumannii and Staphylococcus aureus as well. The specificity
of our molecules to efflux pump inhibition was confirmed using ethidium bromide
accumulation assays, and in studies with strains that displayed varying abilities
in their efflux potential. When assessing off target effects we observed no
disruption of bacterial membrane polarity, no general toxicity toward mammalian
cells, and no inhibition of calcium channel activity in human kidney cells.
Finally, combination treatment with our lead agents engendered a marked increase
in the bactericidal capacity of tetracycline, and significantly decreased
viability within P. aeruginosa biofilms. As such, we report a unique polyamine
scaffold that has strong potential for the future development of novel and
broadly active efflux pump inhibitors targeting multi-drug resistant bacterial
infections.
PMID- 29963038
TI - Clinical, Immunological, and Molecular Findings in Four Cases of B Cell Expansion
With NF-kappaB and T Cell Anergy Disease for the First Time From India.
AB - B cell expansion with NF-kappaB and T cell anergy (BENTA) is a rare primary
immunodeficiency disorder caused by mutations in the CARD11 gene and results in
constitutive NF-kappaB activation in B and T cells. Affected patients present
with polyclonal expansion of B cells at an early age with splenomegaly,
lymphadenopathy, and mild autoimmunity. Here, we discuss four BENTA cases with
unusual clinical manifestations not previously reported. All patients showed
previously reported gain-of-function mutations (G123S, G123D, and C49Y) in the
CARD11 gene. Severe autoimmune manifestations were noted for the first time in
all our patients.
PMID- 29963039
TI - Non-Coding RNA Mediated Regulation of Allogeneic T Cell Responses After
Hematopoietic Transplantation.
AB - Allogeneic bone marrow transplantation (BMT) is an effective therapy for several
malignant and non-malignant disorders. The precise control of allogeneic T cells
is critical for successful outcomes after BMT. The mechanisms governing desirable
(graft-versus-leukemia) versus undesirable (graft-versus-host disease) allogeneic
responses remain incompletely understood. Non-coding RNAs (ncRNA) are controllers
of gene expression that fine-tune cellular responses. Multiple microRNAs
(miRNAs), a type of ncRNA, have recently been shown to influence allogeneic T
cell responses in both murine models and clinically. Here, we review the role of
various miRNAs that regulate T cell responses, either positively or negatively,
to allo-stimulation and highlight their potential relevance as biomarkers and as
therapeutic targets for improving outcomes after allogeneic BMT.
PMID- 29963040
TI - CD19+ B-Cells, a New Biomarker of Mortality in Hemodialysis Patients.
AB - Background and objectives: Mortality of patients on hemodialysis (HD) remains
very high despite recent improvements in HD techniques. Cardiovascular (CV)
complications and infections are the main causes of death. Some studies suggest
that disturbances in the immune system could play a role in this disproportionate
mortality, through the links of immunity with inflammation and propensity to
infections. However, few studies have addressed the role of lymphocyte
populations and the global and CV mortality of HD patients. Aim: To analyze the
relationship of peripheral blood lymphocyte populations (PBLP) and all-cause and
CV mortality of HD patients. Design setting participants and measurements: We
design a prospective observational single center study in a cohort of HD
prevalent patients. PBLP were analyzed at baseline and after 1 year and patients
were followed for a 5-year period. Main outcomes were all-cause and CV mortality.
Results: One hundred and four patients (51% male, mean age 64.8 +/- 15 years)
were included. Follow-up was 18 (7-47) months. Fifty-five patients (52.8%) died,
main causes of death being CVD (40%) and infections (29.1%). Low total lymphocyte
counts were found in 47 patients (45.2%), and the most frequency lymphopenias
were CD19+ B-cell (57.7%), CD3+ (40.4%), and CD4+ (36.5%). After 1 year, all
determinations were lower except CD56+CD16+CD3- natural killer. Patient survival
was significantly lower in patients with a CD19+ B-cell count < 100 cells/MUL at
baseline as compared to patients with CD19+ B-cell >= 100 cells/MUL counts at the
end of follow-up (16.5 vs 54%, p = 0.003). By multivariable analysis, age,
history of CV disease, Charlson index, a KT/V < 1.2, and a CD19+ B-cell count <
100 cells/MUL at baseline and after 1-year were factors associated with of all
cause mortality. A CD19+ B-cell count < 100 cells/MUL at baseline was associated
with CV mortality. Conclusion: CD19+ B-cell lymphopenia is very common among HD
patients, and it could be an independent predictor of all-cause and CV mortality.
More studies are needed to confirm these findings.
PMID- 29963041
TI - Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted
Antigens for Presentation on MHC Class I.
AB - DC-SIGN is an antigen uptake receptor expressed on dendritic cells (DCs) with
specificity for glycans present on a broad variety of pathogens and is capable of
directing its cargo to MHC-I and MHC-II pathways for the induction of CD8+ and
CD4+ T cell responses, respectively. Therefore, DC-SIGN is a very promising
target for the delivery of antigen for anti-cancer vaccination. Although the
endocytic route leading to MHC-II presentation is characterized to a large
extent, the mechanisms controlling DC-SIGN targeted cross-presentation of
exogenous peptides on MHC-I, are not completely resolved yet. In this paper, we
used imaging flow cytometry and antigen-specific CD8+ T cells to investigate the
intracellular fate of DC-SIGN and its cargo in human DCs. Our data demonstrates
that immature DCs and toll-like receptor 4 (TLR4) stimulated DCs had similar
internalization capacity and were both able to cross-present antigen targeted via
DC-SIGN. Interestingly, simultaneous triggering of TLR4 and DC-SIGN on DCs
resulted in the translocation of cargo to the cytosol, leading to proteasome
dependent processing and increased CD8+ T cell activation. Understanding the
dynamics of DC-SIGN-mediated uptake and processing is essential for the design of
optimal DC-SIGN-targeting vaccination strategies aimed at enhancing CD8+ T cell
responses.
PMID- 29963042
TI - Functional Characterisation and Analysis of the Soluble NKG2D Ligand Repertoire
Detected in Umbilical Cord Blood Plasma.
AB - We previously reported that cord blood plasma (CBP) contains significantly more
soluble NKG2D ligands (sNKG2DLs), such as sMICB and sULBP1, than healthy adult
plasma. Viral infection or malignant transformation upregulates expression of
NKG2D ligand on affected cells, leading to NK group 2, member D (NKG2D)-mediated
natural killer (NK) cell lysis. Conversely, sNKG2DL engagement of NKG2D decreases
NK cell cytotoxicity leading to viral or tumour immune escape. We hypothesised
that sNKG2DLs detected in CBP may represent an additional fetal-maternal
tolerance mechanism. To further understand the role of sNKG2DL in pregnancy and
individual contributions of the various ligand types, we carried out functional
analysis using 181 CBP samples. To test the ability of CBP to suppress the
function of NK cells in vitro, we measured expression of NKG2D, CD107a, and IFN
gamma in NK cells from control donors after exposure to 181 individual CBP
samples and characterised the sMICA, sMICB, and sULBP1 content of each one.
Furthermore, to detect possible allelic differences between samples that may also
affect function, we carried out umbilical cord blood typing for MHC class I
related chain A (MICA) and MHC class I-related chain B (MICB) coding and promoter
allelic types. Strongest functional correlations related to increasing
concentration of exosomal sULBP1, which was present in all CBP samples tested. In
addition, common MICB alleles, such as MICB*005:02, resulted in increased
concentration of sMICB. Interestingly, MICB*005:02 uniquely associated with eight
different promoter types. Among promoter polymorphisms, P2 resulted in the
highest expression of sMICB and P9 the least and was confirmed using luciferase
reporter assays. Higher levels of sMICB associated with lower IFN-gamma
production, indicating that sMICB also suppressed NK cell function. We also
examined the MICA functional dimorphism encoding methionine (met) or valine (val)
at residue 129 associated with strong or weak NKG2D binding, respectively. Most
sMICA associated with val/val, some with met/val but none with met/met and,
counter-intuitively, the presence of sMICA in CBP increased NK cell cytotoxicity.
We propose a model for fetal-maternal tolerance, whereby NK cell activity is
limited by sULBP1 and sMICB in CBP. The release of 129val sMICA with weak NKG2D
signalling may reduce the overall net suppressive signal and break tolerance thus
allowing fetal NK cells to overcome immunological threats in utero.
PMID- 29963043
TI - New Genetically Manipulated Mice Provide Insights Into the Development and
Physiological Functions of Invariant Natural Killer T Cells.
AB - Invariant natural killer T (iNKT) cells are a unique T cell subset that exhibits
characteristics of both innate immune cells and T cells. They express Valpha14
Jalpha18 (Trav11-Traj18) as an invariant chain of the T cell receptor (TCR) and
are restricted to the MHC class I-like monomorphic antigen presenting molecule
CD1d. iNKT cells are known as immune regulators that bridge the innate and
acquired immune systems by rapid and massive production of a wide range of
cytokines, which could enable them to participate in immune responses during
various disease states. Thus, Traj18-deficient mice, Cd1d-deficient mice, or iNKT
cell-overexpressing mice such as iNKT TCRalpha transgenic mice and iNKT cell
cloned mice which contain a Valpha14-Jalpha18 rearrangement in the TCRalpha locus
are useful experimental models for the analysis of iNKT cells in vivo and in
vitro. In this review, we describe the pros and cons of the various available
genetically manipulated mice and summarize the insights gained from their study,
including the possible roles of iNKT cells in obesity and diabetes.
PMID- 29963044
TI - The cGas-Sting Signaling Pathway Is Required for the Innate Immune Response
Against Ectromelia Virus.
AB - Activation of the DNA-dependent innate immune pathway plays a pivotal role in the
host defense against poxvirus. Cyclic GMP-AMP synthase (cGAS) is a key cytosolic
DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon
activation, which triggers stimulator of interferon genes (STING), leading to
type I Interferons (IFNs) production and an antiviral response. Ectromelia virus
(ECTV) has emerged as a valuable model for investigating the host-Orthopoxvirus
relationship. However, the role of cGas-Sting pathway in response to ECTV is not
clearly understood. Here, we showed that murine cells (L929 and RAW264.7) mount
type I IFN responses to ECTV that are dependent upon cGas, Sting, TANK binding
kinase 1 (Tbk1), and interferon regulatory factor 3 (Irf3) signaling. Disruption
of cGas or Sting expression in mouse macrophages blocked the type I IFN
production and facilitated ECTV replication. Consistently, mice deficient in cGas
or Sting exhibited lower type I IFN levels and higher viral loads, and are more
susceptible to mousepox. Collectively, our study indicates that the cGas-Sting
pathway is critical for sensing of ECTV infection, inducing the type I IFN
production, and controlling ECTV replication.
PMID- 29963047
TI - In Search for Reliable Markers of Glioma-Induced Polarization of Microglia.
AB - Immune cells accumulating in the microenvironment of malignant tumors are tumor
educated and contribute to its growth, progression, and evasion of antitumor
immune responses. Glioblastoma (GBM), the common and most malignant primary brain
tumor in adults, shows considerable accumulation of resident microglia and
peripheral macrophages, and their polarization into tumor-supporting cells. There
are controversies regarding a functional phenotype of glioma-associated
microglia/macrophages (GAMs) due to a lack of consistent markers. Previous
categorization of GAM polarization toward the M2 phenotype has been found
inaccurate because of oversimplification of highly complex and heterogeneous
responses. In this study, we characterized functional responses and gene
expression in mouse and human microglial cultures exposed to fresh conditioned
media [glioma-conditioned medium (GCM)] from human U87 and LN18 glioma cells.
Functional analyses revealed mutual communication reflected by strong stimulation
of glioma invasion by microglial cells and increased microglial phagocytosis
after GCM treatment. To define transcriptomic markers of GCM-activated microglia,
we performed selected and global gene expression analyses of stimulated
microglial cells. We found activated pathways associated with immune evasion and
TGF signaling. We performed computational comparison of the expression patterns
of GAMs from human GBMs and rodent experimental gliomas to select genes
consistently changed in different datasets. The analyses of marker genes in GAMs
from different experimental models and clinical samples revealed only a small set
of common genes, which reflects variegated responses in clinical and experimental
settings. Tgm2 and Gpnmb were the only two genes common in the analyzed data
sets. We discuss potential sources of the observed differences and stress a great
need for definitive elucidation of a functional state of GAMs.
PMID- 29963045
TI - MicroRNA-Related Polymorphisms in Infectious Diseases-Tiny Changes With a Huge
Impact on Viral Infections and Potential Clinical Applications.
AB - MicroRNAs (miRNAs) are single-stranded sequences of non-coding RNA with
approximately 22 nucleotides that act posttranscriptionally on gene expression.
miRNAs are important gene regulators in physiological contexts, but they also
impact the pathogenesis of various diseases. The role of miRNAs in viral
infections has been explored by different authors in both population-based as
well as in functional studies. However, the effect of miRNA polymorphisms on the
susceptibility to viral infections and on the clinical course of these diseases
is still an emerging topic. Thus, this review will compile and organize the
findings described in studies that evaluated the effects of genetic variations on
miRNA genes and on their binding sites, in the context of human viral diseases.
In addition to discussing the basic aspects of miRNAs biology, we will cover the
studies that investigated miRNA polymorphisms in infections caused by hepatitis B
virus, hepatitis C virus, human immunodeficiency virus, Epstein-Barr virus, and
human papillomavirus. Finally, emerging topics concerning the importance of miRNA
genetic variants will be presented, focusing on the context of viral infectious
diseases.
PMID- 29963046
TI - The Interleukin-23/Interleukin-17 Axis Links Adaptive and Innate Immunity in
Psoriasis.
AB - Research into the pathophysiology of psoriasis has shed light onto many
fascinating immunological interactions and underlying genetic constellations.
Most prominent among these is the crosstalk between components of the innate and
the adaptive immune system and the crucial role of interleukins (IL)-23 and -17
within this network. While it is clear that IL-23 drives and maintains the
differentiation of Th17 lymphocytes, many aspects of the regulation of IL-23 and
IL-17 are not quite as straightforward and have been unraveled only recently. For
example, we know now that Th17 cells are not the only source of IL-17 but that
cells of the innate immune system also produce considerable amounts of this
central effector cytokine. In addition, there is IL-23-independent production of
IL-17. Besides other innate immune cells, neutrophilic granulocytes prominently
contribute to IL-17-related immune regulations in psoriasis, and it appears that
they employ several mechanisms including the formation of neutrophil
extracellular traps. Here, we strive to put the central role of the IL-23/IL-17
axis into perspective within the crosstalk between components of the innate and
the adaptive immune system. Our aim is to better understand the complex immune
regulation in psoriasis, a disorder that has become a model disease for chronic
inflammation.
PMID- 29963048
TI - Trauma-Induced Damage-Associated Molecular Patterns-Mediated Remote Organ Injury
and Immunosuppression in the Acutely Ill Patient.
AB - Trauma is one of the leading causes of death and disability in the world.
Multiple trauma or isolated traumatic brain injury are both indicative of human
tissue damage. In the early phase after trauma, damage-associated molecular
patterns (DAMPs) are released and give rise to sterile systemic inflammatory
response syndrome (SIRS) and organ failure. Later, protracted inflammation
following sepsis will favor hospital-acquired infection and will worsen patient's
outcome through immunosuppression. Throughout medical care or surgical
procedures, severe trauma patients will be subjected to endogenous or exogenous
DAMPs. In this review, we summarize the current knowledge regarding DAMP-mediated
SIRS or immunosuppression and the clinical consequences in terms of organ failure
and infections.
PMID- 29963049
TI - Human Anti-Als3p Antibodies Are Surrogate Markers of NDV-3A Vaccine Efficacy
Against Recurrent Vulvovaginal Candidiasis.
AB - A Phase 1b/2a clinical trial of NDV-3A vaccine containing a Candida albicans
recombinant Als3 protein formulated with alum protected women <40 years old from
recurrent vulvovaginal candidiasis (RVVC). We investigated the potential use of
anti-Als3p sera as surrogate marker of NDV-3A efficacy. Pre- and post-vaccination
sera from subjects who experienced recurrence of vulvovaginal candidiasis (R) vs.
those who were recurrence-free [non-recurrent (NR)] were evaluated. Anti-Als3p
antisera obtained were evaluated for (1) titer and subclass profile and (2) their
ability to influence C. albicans virulence traits including hyphal elongation,
adherence to plastic, invasion of vaginal epithelial cells, biofilm formation on
plastic and catheter material, and susceptibility to neutrophil killing in vitro.
Serum IgG titers in NR patients were consistently higher than in R patients,
particularly for anti-Als3 subclass IgG2. Sera from vaccinated NR patients
reduced hyphal elongation, adhesion to plastic, invasion of vaginal epithelial
cells, and biofilm formation significantly more than pre-immune sera, or sera
from R- or placebo-group subjects. Pre-adsorption of sera with C. albicans germ
tubes eliminated these effects, while heat inactivation did not. Finally, sera
from NR subjects enhanced neutrophil-mediated killing of C. albicans relative to
pre-immune sera or sera from R patients. Our results suggest that higher Als3p
antibody titers are associated with protection from RVVC, attenuate C. albicans
virulence, and augment immune clearance of the fungus in vitro. Thus, Als3p serum
IgG antibodies are likely useful markers of efficacy in RVVC patients vaccinated
with NDV-3A.
PMID- 29963050
TI - Lower High-Density Lipoproteins Levels During Human Immunodeficiency Virus Type 1
Infection Are Associated With Increased Inflammatory Markers and Disease
Progression.
AB - Introduction: High-density lipoproteins (HDL) are responsible for the efflux and
transport of cholesterol from peripheral tissues to the liver. In addition, HDL
can modulate various immunological mechanisms, including the inflammatory
response. Inflammasomes are multiprotein complexes that have been reported to be
activated during human immunodeficiency virus type 1 (HIV-1) infection, thus
contributing to immune hyperactivation, which is the main pathogenic mechanism of
HIV-1 progression. However, the relationship between HDL and inflammasomes in the
context of HIV-1 infection is unclear. Therefore, this research aims to explore
the association between HDL and the components of the inflammatory response
during HIV-1 infection. Methodology: A cross-sectional study, including 36 HIV-1
infected individuals without antiretroviral treatment and 36 healthy controls
matched by sex and age, was conducted. Viral load, CD4+ T-cell counts, serum HDL,
and C-reactive protein (CRP) were quantified. Serum cytokine levels, including IL
1beta, IL-6, and IL-18, were assessed by ELISA. The inflammasome-related genes in
peripheral blood mononuclear cells were determined by quantitative real-time PCR.
Results: HIV-1-infected individuals showed a significant decrease in HDL levels,
particularly those subjects with higher viral load and lower CD4+ T-cell counts.
Moreover, upregulation of inflammasome-related genes (NLRP3, AIM2, ASC, IL-1beta,
and IL-18) was observed, notably in those HIV-1-infected individuals with higher
viral loads (above 5,000 copies/mL). Serum levels of IL-6 and CRP were also
elevated in HIV-1-infected individuals. Significant negative correlations between
HDL and the mRNA of NLRP3, AIM2, ASC, IL-1beta, and IL-18, as well as viral load
and CRP were observed in HIV-1-infected individuals. Likewise, a significant
positive correlation between HDL and CD4+ T-cell counts was found. Conclusion: In
summary, our results indicate that HDL might modulate the expression of several
key components of the inflammasomes during HIV-1 infection, suggesting a novel
role of HDL in modifying the inflammatory state and consequently, the progression
of HIV-1 infection.
PMID- 29963052
TI - Arsenic Trioxide Enhances the NK Cell Cytotoxicity Against Acute Promyelocytic
Leukemia While Simultaneously Inhibiting Its Bio-Genesis.
AB - Natural killer cells (NK) contribute significantly to eradication of cancer
cells, and there is increased interest in strategies to enhance it's efficacy.
Therapeutic agents used in the treatment of cancer can impact the immune system
in a quantitative and qualitative manner. In this study, we evaluated the impact
of arsenic trioxide (ATO) used in the management of acute promyelocytic leukemia
(APL) on NK cell reconstitution and function. In patients with APL treated with
single agent ATO, there was a significant delay in the reconstitution of
circulating NK cells to reach median normal levels from the time of diagnosis
(655 days for NK cells vs 145 and 265 days for T cells and B cells,
respectively). In vitro experiments demonstrated that ATO significantly reduced
the CD34 hematopoietic stem cell (HSC) differentiation to NK cells. Additional
experimental data demonstrate that CD34+ sorted cells when exposed to ATO lead to
a significant decrease in the expression of IKZF2, ETS1, and TOX transcription
factors involved in NK cell differentiation and maturation. In contrast, exposure
of NK cells and leukemic cells to low doses of ATO modulates NK cell receptors
and malignant cell ligand profile in a direction that enhances NK cell mediated
cytolytic activity. We have demonstrated that NK cytolytic activity toward NB4
cell line when exposed to ATO was significantly higher when compared with
controls. We also validated this beneficial effect in a mouse model of APL were
the median survival with ATO alone and ATO + NK was 44 days (range: 33-46) vs 54
days (range: 52-75). In conclusion, ATO has a differential quantitative and
qualitative effect on NK cell activity. This information can potentially be
exploited in the management of leukemia.
PMID- 29963053
TI - Long-Term Clinical and Immunological Profile of Kidney Transplant Patients Given
Mesenchymal Stromal Cell Immunotherapy.
AB - We report here the long-term clinical and immunological results of four living
donor kidney transplant patients given autologous bone marrow-derived mesenchymal
stromal cells (MSCs) as part of a phase 1 study focused on the safety and
feasibility of this cell therapy. According to study protocols implemented over
time, based on initial early safety findings, the patients were given MSC at day
7 posttransplant (n = 2) or at day -1 pretransplant (n = 2) and received
induction therapy with basiliximab and low-dose rabbit anti-thymocyte globulin
(RATG) or RATG alone, and were maintained on low-dose ciclosporin
(CsA)/mycophenolate mofetil (MMF). All MSC-treated patients had stable graft
function during the 5- to 7-year follow-up, without increased susceptibility to
infections or neoplasm. In three MSC recipients, but not historical control
patients, circulating memory CD8+ T cell percentages remained lower than basal,
coupled with persistent reduction of ex vivo donor-specific cytotoxicity. Two
patients showed a long-lasting increase in the regulatory T cell/memory CD8+ T
cell ratio, paralleled by high circulating levels of naive and transitional B
cells. In one of these two patients, CsA was successfully discontinued, and
currently the low-dose MMF monotherapy is on the tapering phase. The study shows
that MSC therapy is safe in the long term and could promote a pro-tolerogenic
environment in selected patients. Extensive immunomonitoring of MSC-treated
kidney transplant recipients could help selection of patients for safe withdrawal
of maintenance immunosuppressive drugs (NCT00752479 and NCT02012153).
PMID- 29963054
TI - Deficiency of Adenosine Deaminase 2 in Adult Siblings: Many Years of a
Misdiagnosed Disease With Severe Consequences.
AB - Objective: Describe the clinical characteristics and histopathology findings in a
family with two siblings affected with deficiency of adenosine deaminase 2
(DADA2). Both patients presented in childhood with polyarthritis and developed
significant neurological and gastrointestinal features of DADA2 in ear, including
variable degrees of immunologic and hematologic manifestations. Methods:
Adenosine Deaminase 2 (ADA2; also known as cat eye syndrome chromosome region,
candidate 1 gene; CECR1) exon sequencing and serum ADA2 levels were performed to
confirm the diagnosis of DADA2. Comparison of serum adenosine deaminase 2 levels
was made to DADA2 patients, carriers, and healthy controls in Patient 2. Autopsy
specimens from brain and liver tissues were submitted for analysis. Results: Both
patients were found to carry a previously reported rare intronic missense
mutation predicted to affect the transcript splicing (c.973-2A > G; rs139750129)
and an unreported missense mutation p.Val458Asp (c.1373T > A; V458D). Both
brothers started therapy with a tumor necrosis factor inhibitor following the
molecular diagnosis of DADA2 with good response and were eventually tapered off
prednisone. However, Patient 1 died 18 months later due to complications of end
stage liver disease. His autopsy showed evidence for nodular hyperplasia of the
liver often seen in common variable immunodeficiency (CVID) and numerous small,
old infarcts throughout the brain that had not been demonstrated on prior MRI/MRA
imaging. Conclusion: These cases emphasize the importance of recognition of DADA2
in adults, compare CNS imaging modalities to pathologic findings and suggest
similarities in liver pathology between DADA2 and CVID. MRI may not be most
sensitive method to identify small subcortical infarcts in patients suspected to
have DADA2.
PMID- 29963051
TI - Approaches in Immunotherapy, Regenerative Medicine, and Bioengineering for Type 1
Diabetes.
AB - Recent advances on using immune and stem cells as two-pronged approaches for type
1 diabetes mellitus (T1DM) treatment show promise for advancement into clinical
practice. As T1DM is thought to arise from autoimmune attack destroying
pancreatic beta-cells, increasing treatments that use biologics and cells to
manipulate the immune system are achieving better results in pre-clinical and
clinical studies. Increasingly, focus has shifted from small molecule drugs that
suppress the immune system nonspecifically to more complex biologics that show
enhanced efficacy due to their selectivity for specific types of immune cells.
Approaches that seek to inhibit only autoreactive effector T cells or enhance the
suppressive regulatory T cell subset are showing remarkable promise. These modern
immune interventions are also enabling the transplantation of pancreatic islets
or beta-like cells derived from stem cells. While complete immune tolerance and
body acceptance of grafted islets and cells is still challenging, bioengineering
approaches that shield the implanted cells are also advancing. Integrating
immunotherapy, stem cell-mediated beta-cell or islet production and
bioengineering to interface with the patient is expected to lead to a durable
cure or pave the way for a clinical solution for T1DM.
PMID- 29963055
TI - An Expanded Neuroimmunomodulation Axis: sCD83-Indoleamine 2,3-Dioxygenase
Kynurenine Pathway and Updates of Kynurenine Pathway in Neurologic Diseases.
AB - Many neurologic diseases are related to autoimmune dysfunction and a variety of
molecules or reaction pathways are involved in the regulation of immune function
of the nervous system. Soluble CD83 (sCD83) is the soluble form of CD83, a
specific marker of mature dendritic cell, which has recently been shown to have
an immunomodulatory effect. Indoleamine 2,3-dioxygenase (IDO; corresponding
enzyme intrahepatic, tryptophan 2,3-dioxygenase, TDO), a rate-limiting enzyme of
extrahepatic tryptophan kynurenine pathway (KP) participates in the
immunoregulation through a variety of mechanisms solely or with the synergy of
sCD83, and the imbalances of metabolites of KP were associated with immune
dysfunction. With the complement of sCD83 to IDO-KP, a previously known
immunomodulatory axis, this review focused on an expanded neuroimmunomodulation
axis: sCD83-IDO-KP and its involvement in nervous system diseases.
PMID- 29963056
TI - Transforming Growth Factor-beta and Interleukin-10 Synergistically Regulate
Humoral Immunity via Modulating Metabolic Signals.
AB - Inhibitory cytokines, such as transforming growth factor-beta (TGF-beta) and
interleukin-10 (IL-10), are humoral factors involved in the suppressive function
of regulatory T cells and play critical roles in maintaining immune homeostasis.
However, TGF-beta and IL-10 also have pleiotropic effects and induce humoral
immune responses depending on conditions, and thus their therapeutic application
to autoimmune diseases remains limited. Here, we show that a combination of TGF
beta and IL-10, but not single cytokine, is required to suppress B cell
activation induced by toll-like receptor (TLR) stimulation. In in vivo analyses,
the simultaneous presence of TGF-beta and IL-10 effectively suppressed TLR
mediated antigen-specific immune responses and ameliorated pathologies in
imiquimod (TLR7 agonist)-induced lupus model and lupus-prone MRL/lpr mice.
Intriguingly, TGF-beta and IL-10 synergistically modulated transcriptional
programs and suppressed cellular energetics of both glycolysis and oxidative
phosphorylation via inhibition of the mammalian target of rapamycin complex 1
(mTORC1)/S6 kinase 1 (S6K1) pathway in TLR-stimulated B cells. On the other hand,
enhancement of mTOR signaling and mitochondrial biosynthesis in TLR-stimulated B
cells counteracted the synergistic inhibitory effects. The inhibitory cytokine
synergy of TGF-beta and IL-10 via suppression of energy metabolism was also
observed in human TLR-stimulated B cells. There is increasing evidence supporting
the importance of adequate metabolic signals in various immune cells to exert
their immune function. In this study, we have shown that a previously
unrecognized synergy of inhibitory cytokines regulates systemic humoral immune
responses via modulating immunometabolism in B cells. Our findings indicate that
inhibition of B cell metabolism mediated by two synergistic cytokines contributes
to the induction of immune tolerance and could be a new therapeutic strategy for
autoimmune diseases such as systemic lupus erythematosus.
PMID- 29963057
TI - The Conventional Nature of Non-MHC-Restricted T Cells.
AB - The definition "unconventional T cells" identifies T lymphocytes that recognize
non-peptide antigens presented by monomorphic antigen-presenting molecules. Two
cell populations recognize lipid antigens and small metabolites presented by CD1
and MR1 molecules, respectively. A third cell population expressing the TCR
Vgamma9Vdelta2 is stimulated by small phosphorylated metabolites. In the recent
past, we have learnt a lot about the selection, tissue distribution, gene
transcription programs, mode of expansion after antigen recognition, and
persistence of these cells. These studies depict their functions in immune
homeostasis and diseases. Current investigations are revealing that
unconventional T cells include distinct sub-populations, which display unexpected
similarities to classical MHC-restricted T cells in terms of TCR repertoire
diversity, antigen specificity variety, functional heterogeneity, and naive-to
memory differentiation dynamic. This review discusses the latest findings with a
particular emphasis on these T cells, which appear to be more conventional than
previously appreciated, and with the perspective of using CD1 and MR1-restricted
T cells in vaccination and immunotherapy.
PMID- 29963058
TI - Functional Plasticity of Gamma Delta T Cells and Breast Tumor Targets in Hypoxia.
AB - Interactions between immune and tumor cells in the tumor microenvironment (TME)
often impact patient outcome, yet remain poorly understood. In addition, the
effects of biophysical features such as hypoxia [low oxygen (O2)] on cells within
the TME may lead to tumor evasion. Gamma delta T cells (gammadeltaTcs) naturally
kill transformed cells and are therefore under development as immunotherapy for
various cancers. Clinical trials have proven the safety of gammadeltaTc
immunotherapy and increased circulating gammadeltaTc levels correlate with
improved patient outcome. Yet, the function of gammadeltaTc tumor infiltrating
lymphocytes in human breast cancer remains controversial. Breast tumors can be
highly hypoxic, thus therapy must be effective under low O2 conditions. We have
found increased infiltration of gammadeltaTc in areas of hypoxia in a small
cohort of breast tumors; considering their inherent plasticity, it is important
to understand how hypoxia influences gammadeltaTc function. In vitro, the cell
density of expanded primary healthy donor blood-derived human gammadeltaTc
decreased in response to hypoxia (2% O2) compared to normoxia (20% O2). However,
the secretion of macrophage inflammatory protein 1alpha (MIP1alpha)/MIP1beta,
regulated on activation, normal T cell expressed and secreted (RANTES), and CD40L
by gammadeltaTc were increased after 40 h in hypoxia compared to normoxia
concomitant with the stabilization of hypoxia inducible factor 1-alpha protein.
Mechanistically, we determined that natural killer group 2, member D (NKG2D) on
gammadeltaTc and the NKG2D ligand MHC class I polypeptide-related sequence A
(MICA)/B on MCF-7 and T47D breast cancer cell lines are important for
gammadeltaTc cytotoxicity, but that MIP1alpha, RANTES, and CD40L do not play a
direct role in cytotoxicity. Hypoxia appeared to enhance the cytotoxicity of
gammadeltaTc such that exposure for 48 h increased cytotoxicity of gammadeltaTc
against breast cancer cells that were maintained in normoxia; conversely, breast
cancer lines incubated in hypoxia for 48 h prior to the assay were largely
resistant to gammadeltaTc cytotoxicity. MICA/B surface expression on both MCF-7
and T47D remained unchanged upon exposure to hypoxia; however, ELISAs revealed
increased MICA shedding by MCF-7 under hypoxia, potentially explaining resistance
to gammadeltaTc cytotoxicity. Despite enhanced gammadeltaTc cytotoxicity upon pre
incubation in hypoxia, these cells were unable to overcome hypoxia-induced
resistance of MCF-7. Thus, such resistance mechanisms employed by breast cancer
targets must be overcome to develop more effective gammadeltaTc immunotherapies.
PMID- 29963059
TI - Predicting HLA CD4 Immunogenicity in Human Populations.
AB - Background: Prediction of T cell immunogenicity is a topic of considerable
interest, both in terms of basic understanding of the mechanisms of T cells
responses and in terms of practical applications. HLA binding affinity is often
used to predict T cell epitopes, since HLA binding affinity is a key requisite
for human T cell immunogenicity. However, immunogenicity at the population it is
complicated by the high level of variability of HLA molecules, potential other
factors beyond HLA as well as the frequent lack of HLA typing data. To overcome
those issues, we explored an alternative approach to identify the common
characteristics able to distinguish immunogenic peptides from non-recognized
peptides. Methods: Sets of dominant epitopes derived from peer-reviewed published
papers were used in conjunction with negative peptides from the same
experiments/donors to train neural networks and generate an "immunogenicity
score." We also compared the performance of the immunogenicity score with
previously described method for immunogenicity prediction based on HLA class II
binding at the population level. Results: The immunogenicity score was validated
on a series of independent datasets derived from the published literature,
representing 57 independent studies where immunogenicity in human populations was
assessed by testing overlapping peptides spanning different antigens. Overall,
these testing datasets corresponded to over 2,000 peptides and tested in over
1,600 different human donors. The 7-allele method prediction and the
immunogenicity score were associated with similar performance [average area under
the ROC curve (AUC) values of 0.703 and 0.702, respectively] while the combined
methods reached an average AUC of 0.725. This increase in average AUC value is
significant compared with the immunogenicity score (p = 0.0135) and a strong
trend toward significance is observed when compared to the 7-allele method (p =
0.0938). The new immunogenicity score method is now freely available using CD4 T
cell immunogenicity prediction tool on the Immune Epitope Database website
(http://tools.iedb.org/CD4episcore). Conclusion: The new immunogenicity score
predicts CD4 T cell immunogenicity at the population level starting from protein
sequences and with no need for HLA typing. Its efficacy has been validated in the
context of different antigen sources, ethnicities, and disparate techniques for
epitope identification.
PMID- 29963060
TI - T Cell Repertoire Maturation Induced by Persistent and Latent Viral Infection Is
Insufficient to Induce Costimulation Blockade Resistant Organ Allograft Rejection
in Mice.
AB - CD28:CD80/86 pathway costimulation blockade (CoB) with the CD80/86-specific
fusion protein CTLA4-Ig prevents T cell-mediated allograft rejection in mice.
However, in humans, transplantation with CoB has been hampered by CoB-resistant
rejection (CoBRR). CoBRR has been attributed in part to pathogen-driven T cell
repertoire maturation and resultant heterologous alloreactive memory. This has
been demonstrated experimentally in mice. However, prior murine models have used
viral pathogens, CoB regimens, graft types, and/or antigen systems atypically
encountered clinically. We therefore sought to explore whether CoBRR would emerge
in a model of virus-induced memory differentiation designed to more closely mimic
clinical conditions. Specifically, we examined mouse homologs of clinically
prevalent viruses including murine polyomavirus, cytomegalovirus, and
gammaherpesvirus 68 in the presence of clinically relevant maintenance CoB
regimens using a fully MHC-mismatched, vascularized allograft model. Infected
mice developed a significant, sustained increase in effector memory T cells
consistent with that seen in humans, but neither developed heterologous
alloreactivity nor rejected primarily vascularized heterotopic heart transplants
at an increased rate compared with uninfected mice. These results indicate that
memory acquisition alone is insufficient to provoke CoBRR and suggest that
knowledge of prior latent or persistent viral infection may have limited utility
in anticipating heterologous CoB-resistant alloimmunity.
PMID- 29963061
TI - gammadelta T Cells and Tumor Microenvironment: From Immunosurveillance to Tumor
Evasion.
AB - gammadelta T cells possess cytotoxic antitumor activity mediated by production of
proinflammatory cytokines, direct cytotoxic activity, and regulation of the
biological functions of other cell types. Hence, these features have prompted the
development of therapeutic strategies in which gammadelta T cells agonists or ex
vivo-expanded gammadelta T cells are administered to tumor patients. Several
studies have shown that gammadelta T cells are an important component of tumor
infiltrating lymphocytes in patients affected by different types of cancer and a
recent analysis of ~18,000 transcriptomes from 39 human tumors identified tumor
infiltrating gammadelta T cells as the most significant favorable cancer-wide
prognostic signature. However, the complex and intricate interactions between
tumor cells, tumor microenvironment (TME), and tumor-infiltrating immune cells
results in a balance between tumor-promoting and tumor-controlling effects, and
gammadelta T cells functions are often diverted or impaired by immunosuppressive
signals originating from the TME. This review focuses on the dangerous liason
between gammadelta T cells and tumoral microenvironment and raises the
possibility that strategies capable to reduce the immunosuppressive environment
and increase the cytotoxic ability of gammadelta T cells may be the key factor to
improve their utilization in tumor immunotherapy.
PMID- 29963062
TI - Diversity of Drought Tolerance in the Genus Vigna.
AB - Wild relatives of crop plants are thought as reservoir of prominent genetic
resources for abiotic stress tolerance. However, insufficient information on
genetic variation and phenotypic traits restricts their use for crop breeding.
This study focused on wild species of genus Vigna (family Fabaceae) originated
from highly humid to arid regions. To clarify the diversity of drought tolerance
during the vegetative stage, 69 accessions, including 15 domesticated, and 54
wild accessions, were evaluated under two drought conditions of non-terminal and
terminal stresses. In the non-terminal drought condition, the plants were grown
in pipes of different heights where surface soil water content decreased faster
in pipes with greater height. Relative shoot biomass was used for tolerance
evaluation and we identified 19 drought tolerant accessions. Almost of them were
wild accessions showing higher relative shoot biomass than that in the
domesticated accessions. Domesticated species were mostly classified as drought
susceptible but could be improved using tolerant conspecific wild ancestors with
cross-compatibility. The tolerance was related with higher plant water status
presumably due to small water consumption. However, the variation of drought
tolerance could not be explained by simple tolerance factor alone, and other
tolerance mechanisms such as deep rooting and increasing in root biomass were
found in the tolerant accessions. In the terminal drought condition, the plants
were grown in small pots, and the watering was stopped to expose them extreme and
rapid soil water scarcity. The tolerance was evaluated as the number of days
until wilting. However, the accessions found to be tolerant in the pot experiment
were not the same as those in the pipe experiment. In this condition, plant water
status was not related with the length of days to wilting. This indicates that
different mechanisms are necessary for adaptation to each of the non-terminal and
terminal drought conditions. Many accessions were tolerant to one of the
conditions, although we identified that some accessions showed tolerance in both
experiments. The great diversity in drought tolerance in the genus Vigna might
serve to both improve crop drought tolerance and understand the mechanisms of
adaptation in drought-prone environments.
PMID- 29963063
TI - Proteome Analysis of Potato Starch Reveals the Presence of New Starch Metabolic
Proteins as Well as Multiple Protease Inhibitors.
AB - Starch bound proteins mainly include enzymes from the starch biosynthesis
pathway. Recently, new functions in starch molecular assembly or active protein
targeting were also proposed for starch associated proteins. The potato genome
sequence reveals 77 loci encoding starch metabolizing enzymes with the
identification of previously unknown putative isoforms. Here we show by bottom-up
proteomics that most of the starch biosynthetic enzymes in potato remain
associated with starch even after washing with SDS or protease treatment of the
granule surface. Moreover, our study confirmed the presence of PTST1 (Protein
Targeting to Starch), ESV1 (Early StarVation1) and LESV (Like ESV), that have
recently been identified in Arabidopsis. In addition, we report on the presence
of a new isoform of starch synthase, SS6, containing both K-X-G-G-L catalytic
motifs. Furthermore, multiple protease inhibitors were also identified that are
cleared away from starch by SDS and thermolysin treatments. Our results indicate
that SS6 may play a yet uncharacterized function in starch biosynthesis and open
new perspectives both in understanding storage starch metabolism as well as
breeding improved potato lines.
PMID- 29963064
TI - The Active Jasmonate JA-Ile Regulates a Specific Subset of Plant Jasmonate
Mediated Resistance to Herbivores in Nature.
AB - The jasmonate hormones are essential regulators of plant defense against
herbivores and include several dozen derivatives of the oxylipin jasmonic acid
(JA). Among these, the conjugate jasmonoyl isoleucine (JA-Ile) has been shown to
interact directly with the jasmonate co-receptor complex to regulate responses to
jasmonate signaling. However, functional studies indicate that some aspects of
jasmonate-mediated defense are not regulated by JA-Ile. Thus, it is not clear
whether JA-Ile is best characterized as the master jasmonate regulator of
defense, or if it regulates more specific aspects. We investigated possible
functions of JA-Ile in anti-herbivore resistance of the wild tobacco Nicotiana
attenuata, a model system for plant-herbivore interactions. We first analyzed the
soluble and volatile secondary metabolomes of irJAR4xirJAR6, asLOX3, and WT
plants, as well as an RNAi line targeting the jasmonate co-receptor CORONATINE
INSENSITIVE 1 (irCOI1), following a standardized herbivory treatment.
irJAR4xirJAR6 were the most similar to WT plants, having a ca. 60% overlap in
differentially regulated metabolites with either asLOX3 or irCOI1. In contrast,
while at least 25 volatiles differed between irCOI1 or asLOX3 and WT plants,
there were few or no differences in herbivore-induced volatile emission between
irJAR4xirJAR6 and WT plants, in glasshouse- or field-collected samples. We then
measured the susceptibility of jasmonate-deficient vs. JA-Ile-deficient plants in
nature, in comparison to wild-type (WT) controls, and found that JA-Ile-deficient
plants (irJAR4xirJAR6) are much better defended even than a mildly jasmonate
deficient line (asLOX3). The differences among lines could be attributed to
differences in damage from specific herbivores, which appeared to prefer either
one or the other jasmonate-deficient phenotype. We further investigated the
elicitation of one herbivore-induced volatile known to be jasmonate-regulated and
to mediate resistance to herbivores: (E)-alpha-bergamotene. We found that JA was
a more potent elicitor of (E)-alpha-bergamotene emission than was JA-Ile, and
when treated with JA, irJAR4xirJAR6 plants emitted 20- to 40-fold as much (E)
alpha-bergamotene than WT. We conclude that JA-Ile regulates specific aspects of
herbivore resistance in N. attenuata. This specificity may allow plants
flexibility in their responses to herbivores and in managing trade-offs between
resistance, vs. growth and reproduction, over the course of ontogeny.
PMID- 29963066
TI - Development and Evaluation of Low Phytic Acid Soybean by siRNA Triggered Seed
Specific Silencing of Inositol Polyphosphate 6-/3-/5-Kinase Gene.
AB - Soybean is one of the leading oilseed crop in the world and is showing a
remarkable surge in its utilization in formulating animal feeds and supplements.
Its dietary consumption, however, is incongruent with its existing industrial
demand due to the presence of anti-nutritional factors in sufficiently large
amounts. Phytic acid in particular raises concern as it causes a concomitant loss
of indigestible complexed minerals and charged proteins in the waste and results
in reduced mineral bioavailability in both livestock and humans. Reducing the
seed phytate level thus seems indispensable to overcome the nutritional menace
associated with soy grain consumption. In order to conceive our objective we
designed and expressed a inositol polyphosphate 6-/3-/5-kinase gene-specific RNAi
construct in the seeds of Pusa-16 soybean cultivar. We subsequently conducted a
genotypic, phenotypic and biochemical analysis of the developed putative
transgenic populations and found very low phytic acid levels, moderate
accumulation of inorganic phosphate and elevated mineral content in some lines.
These low phytic acid lines did not show any reduction in seedling emergence and
displayed an overall good agronomic performance.
PMID- 29963065
TI - Investigation of Baseline Iron Levels in Australian Chickpea and Evaluation of a
Transgenic Biofortification Approach.
AB - Iron deficiency currently affects over two billion people worldwide despite
significant advances in technology and society aimed at mitigating this global
health problem. Biofortification of food staples with iron (Fe) represents a
sustainable approach for alleviating human Fe deficiency in developing countries,
however, biofortification efforts have focused extensively on cereal staples
while pulses have been largely overlooked. In this study we describe a genetic
engineering (GE) approach to biofortify the pulse crop, chickpea (Cicer arietinum
L.), with Fe using a combination of the chickpea nicotianamine synthase 2
(CaNAS2) and soybean (Glycine max) ferritin (GmFER) genes which function in Fe
transport and storage, respectively. This study consists of three main
components: (1) the establishment for baseline Fe concentration of existing
germplam, (2) the isolation and study of expression pattern of the novel CaNAS2
gene, and (3) the generation of GE chickpea overexpressing the CaNAS2 and GmFER
genes. Seed of six commercial chickpea cultivars was collected from four
different field locations in Australia and assessed for seed Fe concentration.
The results revealed little difference between the cultivars assessed, and that
chickpea seed Fe was negatively affected where soil Fe bioavailability is low.
The desi cultivar HatTrick was then selected for further study. From it, the
CaNAS2 gene was cloned and its expression in different tissues examined. The gene
was found to be expressed in multiple vegetative tissues under Fe-sufficient
conditions, suggesting that it may play a housekeeping role in systemic
translocation of Fe. Two GE chickpea events were then generated and the
overexpression of the CaNAS2 and GmFER transgenes confirmed. Analysis of
nicotianamine (NA) and Fe levels in the GE seeds revealed that NA was nearly
doubled compared to the null control while Fe concentration was not changed.
Increased NA content in chickpea seed is likely to translate into increased Fe
bioavailability and may thus overcome the effect of the bioavailability
inhibitors found in pulses; however, further study is required to confirm this.
This is the first known example of GE Fe biofortified chickpea; information
gleaned from this study can feed into future pulse biofortification work to help
alleviate global Fe deficiency.
PMID- 29963067
TI - Pre-harvest Sprouting and Grain Dormancy in Sorghum bicolor: What Have We
Learned?
AB - The possibility of obtaining sorghum grains with quality to match the standards
for a diversity of end-uses is frequently hampered by the susceptibility to pre
harvest sprouting (PHS) displayed by many elite genotypes. For these reasons,
obtaining resistance to PHS is considered in sorghum breeding programs,
particularly when the crop is expected to approach harvest maturity under rainy
or damp conditions prevalence. As in other cereals, the primary cause for
sprouting susceptibility is a low dormancy prior to crop harvest; in consequence,
most research has focused in understanding the mechanisms through which the
duration of dormancy is differentially controlled in genotypes with contrasting
sprouting behavior. With this aim two tannin-less, red-grained inbred lines were
used as a model system: IS9530 (sprouting resistant) and Redland B2 (sprouting
susceptible). Redland B2 grains are able to germinate well before reaching
physiological maturity (PM) while IS9530 ones can start to germinate at 40-45
days after pollination, well after PM. Results show that the anticipated dormancy
loss displayed by Redland B2 grains is related reduced embryo sensitivity to
abscisic acid (ABA) and increased levels of GA upon imbibition. In turn,
transcriptional data showed that ABA signal transduction is impaired in Redland
B2, which appears to have an impact on GA catabolism, thus affecting the overall
GA/ABA balance that regulates germination. QTL analyses were conducted to test
whether previous candidate genes were located in a dormancy QTL, but also to
identify new genes involved in dormancy. These analyses yielded several dormancy
QTL and one of them located in chromosome 9 (qGI-9) was consistently detected
even across environments. Fine mapping is already in progress to narrow down the
number of candidate genes in qGI-9.
PMID- 29963068
TI - Editorial: Novel Aspects of Nucleolar Functions in Plant Growth and Development.
PMID- 29963069
TI - Construction of a SNP-Based High-Density Genetic Map Using Genotyping by
Sequencing (GBS) and QTL Analysis of Nut Traits in Chinese Chestnut (Castanea
mollissima Blume).
AB - Chinese chestnut is a wildly distributed nut species with importantly economic
value. The nut size and ripening period are mainly desired breeding objectives in
Chinese chestnut. However, high-density linkage maps and quantitative trait loci
(QTL) analyses related to nut traits are less than satisfactory, which hinders
progress in the breeding of Chinese chestnut. Here, a single nucleotide
polymorphism (SNP)-based high-density linkage map was constructed through
genotyping-by-sequencing (GBS) of an F1 cross between the two widely grown
Chinese chestnut cultivars 'Yanshanzaofeng' and 'Guanting No. 10'. The genetic
linkage map consists of 2,620 SNP markers with a total length of 1078.06 cM in 12
linkage groups (LGs) and an average marker distance of 0.41 cM. 17 QTLs were
identified for five nut traits, specifically single-nut weight (SNW), nut width
(NW), nut thickness (NT), nut height (NH), and ripening period (RP), based on
phenotypic data from two successive years. Of the 17 QTLs, two major QTLs, i.e.,
qNT-I-1 and qRP-B-1 related to the NT and RP traits, respectively, were
exploited. Moreover, the data revealed one pleiotropic QTL at 23.97 cM on LG I,
which might simultaneously control SNW, NT, and NW. This study provides useful
benchmark information concerning high-density genetic mapping and QTLs
identification related to nut size and ripening period, and will accelerate
genetic improvements for nuts in the marker-assisted selection (MAS) breeding of
Chinese chestnut.
PMID- 29963070
TI - Targeted Proteomics Approach Toward Understanding the Role of the Mitochondrial
Protease FTSH4 in the Biogenesis of OXPHOS During Arabidopsis Seed Germination.
AB - Seed germination provides an excellent model to study the process of
mitochondrial biogenesis. It is a complex and strictly regulated process which
requires a proper biogenesis of fully active organelles from existing
promitochondrial structures. We have previously reported that the lack of the
inner mitochondrial membrane protease FTSH4 delayed Arabidopsis seed germination.
Here, we implemented a targeted mass spectrometry-based approach, Multiple
Reaction Monitoring (MRM), with stable-isotope-labeled standard peptides for
increased sensitivity, to quantify mitochondrial proteins in dry and germinating
wild-type and ftsh4 mutant seeds, lacking the FTSH4 protease. Using total seed
protein extracts we measured the abundance of the peptide targets belonging to
the OXPHOS complexes, AOX1A, transport, and inner membrane scaffold as well as
mitochondrial proteins that are highly specific to dry and germinating seeds. The
MRM assay showed that the abundance of these proteins in ftsh4 did not differ
substantially from that observed in wild-type at the level of dry seed and after
stratification, but we observed a reduction in protein abundance in most of the
examined OXPHOS subunits in the later stages of germination. These changes in
OXPHOS protein levels in ftsh4 mutants were accompanied by a lower cytochrome
pathway activity as well as an increased AOX1A amount at the transcript and
protein level and alternative pathway activity. The analyses of the steady-state
transcript levels of mitochondrial and nuclear genes encoding OXPHOS subunits did
not show significant difference in their amount, indicating that the observed
changes in the OXPHOS occurred at the post-transcriptional level. At the time
when ftsh4 seeds were fully germinated, the abundance of the OXPHOS proteins in
the mutant was either slightly lowered or comparable to these amounts in wild
type seeds at the similar developmental stage. By the implementation of an
integrative approach combining targeted proteomics, quantitative transcriptomics,
and physiological studies we have shown that the FTSH4 protease has an important
role in the biogenesis of OXPHOS and thus biogenesis of mitochondria during
germination of Arabidopsis seeds.
PMID- 29963071
TI - Detection of Significant Association Between Variants in Cannabinoid Receptor 1
Gene (CNR1) and Personality in African-American Population.
AB - Background: Several studies have revealed significant associations between single
nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 (CNR1) gene and a
broad spectrum of psychiatric disorders such as major depressive disorder (MDD),
attention deficit hyperactivity disorder (ADHD), and schizophrenia. Personality
traits that are highly related to susceptibility to these conditions have been
associated with the CNR1 variants in subjects of Caucasian origin. However, there
are no reported studies regarding the effects of CNR1 polymorphisms on
personality traits in the African-American (AA) population. Methods: We performed
an imputation-based association analysis for 26 CNR1 variants with five
dimensions of personality in 3,046 AAs. Results: SNPs rs806372 and rs2180619
showed a significant association with extraversion after Bonferroni correction
for multiple testing (p < 0.0019). Further, several extraversion-associated SNPs
were significantly associated with conscientiousness, agreeableness, and
openness. SNP priority score analysis indicated that SNPs rs806368, rs806371, and
rs2180619 play a role in the modulation of personality and psychiatric
conditions. Conclusion:CNR1 is important in determining personality traits in the
AA population.
PMID- 29963072
TI - Sex-Dependent Effects of the Histone Deacetylase Inhibitor, Sodium Valproate, on
Reversal Learning After Developmental Arsenic Exposure.
AB - Several studies have demonstrated that exposure to arsenic in drinking water
adversely affects brain development and cognitive function in adulthood. While
the mechanism by which arsenic induces adverse neurological outcomes remains
elusive, studies suggest a link between reduced levels of histone acetylation and
impaired performance on a variety of behavioral tasks following arsenic exposure.
Using our developmental arsenic exposure (DAE) paradigm, we have previously
reported reduced histone acetylation and associated histone acetyltransferase
enzyme expression in the frontal cortex of C57BL/6J adult male mice, with no
changes observed in the female frontal cortex. In the present study, we sought to
determine if DAE produced sex-dependent deficits in frontal cortical executive
function using the Y-maze acquisition and reversal learning tasks, which are
specific for assessing cognitive flexibility. Further, we tested whether the
administration of valproic acid, a class I-IIa histone deacetylase inhibitor, was
able to mitigate behavioral and biochemical changes resulting from DAE. As
anticipated, DAE inhibited acquisition and reversal learning performance in adult
male, but not female, mice. Valproate treatment for 2 weeks restored reversal
performance in the male arsenic-exposed offspring, while not affecting female
performance. Protein levels of HDACs 1, 2, and 5 were elevated following
behavioral assessment but only in DAE male mice; restoration of appropriate HDAC
levels occurred after valproate treatment and was concurrent with improved
behavioral performance, particularly during reversal learning. Female frontal
cortical levels of HDAC enzymes were not impacted by DAE or valproate treatment.
Finally, mRNA expression levels of brain-derived neurotrophic factor, Bdnf, which
has been implicated in the control of frontal cortical flexibility and is
regulated by HDAC5, were elevated in DAE male mice and restored to normal levels
following HDACi treatment. Levels of mRNA encoding glutamate receptor ionotropic
NMDA type subunits, which have been linked to cognitive flexibility, were not
related to the reversal learning deficit in the DAE mice and were not altered by
HDACi treatments. These findings demonstrate that DAE alters frontal cortical
HDAC levels and Bdnf expression in males, but not females, and that these
molecular changes are associated with sex-dependent differences in cognitive
flexibility in a reversal-learning task.
PMID- 29963073
TI - Combining Pathway Identification and Breast Cancer Survival Prediction via
Screening-Network Methods.
AB - Breast cancer is one of the most common invasive tumors causing high mortality
among women. It is characterized by high heterogeneity regarding its biological
and clinical characteristics. Several high-throughput assays have been used to
collect genome-wide information for many patients in large collaborative studies.
This knowledge has improved our understanding of its biology and led to new
methods of diagnosing and treating the disease. In particular, system biology has
become a valid approach to obtain better insights into breast cancer biological
mechanisms. A crucial component of current research lies in identifying novel
biomarkers that can be predictive for breast cancer patient prognosis on the
basis of the molecular signature of the tumor sample. However, the high dimension
and low sample size of data greatly increase the difficulty of cancer survival
analysis demanding for the development of ad-hoc statistical methods. In this
work, we propose novel screening-network methods that predict patient survival
outcome by screening key survival-related genes and we assess the capability of
the proposed approaches using METABRIC dataset. In particular, we first identify
a subset of genes by using variable screening techniques on gene expression data.
Then, we perform Cox regression analysis by incorporating network information
associated with the selected subset of genes. The novelty of this work consists
in the improved prediction of survival responses due to the different types of
screenings (i.e., a biomedical-driven, data-driven and a combination of the two)
before building the network-penalized model. Indeed, the combination of the two
screening approaches allows us to use the available biological knowledge on
breast cancer and complement it with additional information emerging from the
data used for the analysis. Moreover, we also illustrate how to extend the
proposed approaches to integrate an additional omic layer, such as copy number
aberrations, and we show that such strategies can further improve our prediction
capabilities. In conclusion, our approaches allow to discriminate patients in
high-and low-risk groups using few potential biomarkers and therefore, can help
clinicians to provide more precise prognoses and to facilitate the subsequent
clinical management of patients at risk of disease.
PMID- 29963074
TI - Rare Case of Ulnar-Mammary-Like Syndrome With Left Ventricular Tachycardia and
Lack of TBX3 Mutation.
AB - "Heart-hand" type syndromes represent a group of rare congenital conditions that
combine cardiac pathology (structural defect or arrhythmic disorder) and limb
abnormality. Significant clinical variability and genetic heterogeneity typical
for such syndromes complicate correct diagnosis, prognosis, and appropriate
genetic counseling of the affected families. By now, only single genes have been
unambiguously determined as a genetic cause of heart-hand syndromes and
phenotypically similar conditions. In the present study, we report on a 25-year
old Russian female patient with a clinical picture resembling ulnar-mammary
syndrome (UMS). Principal clinical manifestations included heart septal fibrosis
and non-sustained left ventricular tachycardia combined with fifth finger
camptodactyly, hypoplastic breast, abnormal teeth, and mental retardation. Target
Sanger sequencing and array-based comparative genome hybridization confirmed the
lack of pathogenic mutations and large-scale deletions in TBX3 (12q24.21), the
only gene known to be associated with UMS cases to date. Based on the results of
whole-exome sequencing, 14 potential candidate variants were identified. Among
them, a novel missense variant in SYNM gene (exon 1, c.173C > T, p.A58V),
encoding intermediate filament protein synemin was characterized. Until the
present, no association between SYNM mutations and congenital clinical syndromes
has been reported. At the same time, taking into account synemin tissue-specific
expression profiles and available data on abnormal knock-out mice phenotypes, we
propose SYNM as a candidate gene contributing to the UMS-like phenotype. Further
comprehensive functional studies are required to evaluate possible involvement of
SYNM in genesis of complex heart-limb pathology.
PMID- 29963075
TI - Jointly Modelling Single Nucleotide Polymorphisms With Longitudinal and Time-to
Event Trait: An Application to Type 2 Diabetes and Fasting Plasma Glucose.
AB - In observational cohorts, longitudinal data are collected with repeated
measurements at predetermined time points for many biomarkers, along with other
variables measured at baseline. In these cohorts, time until a certain event of
interest occurs is reported and very often, a relationship will be observed
between some biomarker repeatedly measured over time and that event. Joint models
were designed to efficiently estimate statistical parameters describing this
relationship by combining a mixed model for the longitudinal biomarker trajectory
and a survival model for the time until occurrence of the event, using a set of
random effects to account for the relationship between the two types of data. In
this paper, we discuss the implementation of joint models in genetic association
studies. First, we check model consistency based on different simulation
scenarios, by varying sample sizes, minor allele frequencies and number of
repeated measurements. Second, using genotypes assayed with the Metabochip DNA
arrays (Illumina) from about 4,500 individuals recruited in the French cohort
D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance
syndrome), we assess the feasibility of implementing the joint modelling approach
in a real high-throughput genomic dataset. An alternative model approximating the
joint model, called the Two-Step approach (TS), is also presented. Although the
joint model shows more precise and less biased estimators than its alternative
counterpart, the TS approach results in much reduced computational times, and
could thus be used for testing millions of SNPs at the genome-wide scale.
PMID- 29963076
TI - Revisiting Meiosis in Sugarcane: Chromosomal Irregularities and the Prevalence of
Bivalent Configurations.
AB - Traditional sugarcane cultivars (Saccharum officinarum) proved highly susceptible
to diseases, and this led breeders to progress to interspecific crosses resulting
in disease resistance. A backcrossing program to S. officinarum was then required
to boost sucrose content. Clonal selection across generations and incorporation
of other germplasm into cultivated backgrounds established the (narrow) genetic
base of modern cultivars (Saccharum spp.), which have a man-made genome. The
genome complexity has inspired several molecular studies that have elucidated
aspects of sugarcane genome constitution, architecture, and cytogenetics.
However, there is a critical shortage of information on chromosome behavior
throughout meiosis in modern cultivars. In this study, we examined the
microsporogenesis of a contemporary variety, providing a detailed analysis of the
meiotic process and chromosome association at diakinesis, using FISH with
centromeric probes. Chromosomal abnormalities were documented by examining high
quality preparations of pollen mother cells (700 in total). Approximately 70% of
the cells showed abnormalities, such as metaphase chromosomes not lined up at the
plate, lagging chromosomes and chromosomal bridges, and tetrad cells with
micronuclei. Some dyads with asynchronous behavior were also observed. Due to the
hybrid composition of the sugarcane genome, we suggest that bivalent incomplete
pairing may occur in the first prophase leading to univalency. The presence of
rod bivalents showing the lagging tendency is consistent with a reduction in
chiasma frequency. Finally, the presence of chromatin bridges indicates the
indirect occurrence of chromosomal inversions, although chromosome fragments were
not clearly recognized. Possible reasons for such meiotic abnormalities and the
large prevalence of bivalent formation are discussed.
PMID- 29963077
TI - PASSPORT-seq: A Novel High-Throughput Bioassay to Functionally Test Polymorphisms
in Micro-RNA Target Sites.
AB - Next-generation sequencing (NGS) studies have identified large numbers of genetic
variants that are predicted to alter miRNA-mRNA interactions. We developed a
novel high-throughput bioassay, PASSPORT-seq, that can functionally test in
parallel 100s of these variants in miRNA binding sites (mirSNPs). The results are
highly reproducible across both technical and biological replicates. The utility
of the bioassay was demonstrated by testing 100 mirSNPs in HEK293, HepG2, and
HeLa cells. The results of several of the variants were validated in all three
cell lines using traditional individual luciferase assays. Fifty-five mirSNPs
were functional in at least one of three cell lines (FDR <= 0.05); 11, 36, and 27
of them were functional in HEK293, HepG2, and HeLa cells, respectively. Only four
of the variants were functional in all three cell lines, which demonstrates the
cell-type specific effects of mirSNPs and the importance of testing the mirSNPs
in multiple cell lines. Using PASSPORT-seq, we functionally tested 111 variants
in the 3' UTR of 17 pharmacogenes that are predicted to alter miRNA regulation.
Thirty-three of the variants tested were functional in at least one cell line.
PMID- 29963078
TI - Coupling of organic and inorganic aerosol systems and the effect on gas-particle
partitioning in the southeastern US.
AB - Several models were used to describe the partitioning of ammonia, water, and
organic compounds between the gas and particle phases for conditions in the
southeastern US during summer 2013. Existing equilibrium models and frameworks
were found to be sufficient, although additional improvements in terms of
estimating pure-species vapor pressures are needed. Thermodynamic model
predictions were consistent, to first order, with a molar ratio of ammonium to
sulfate of approximately 1.6 to 1.8 (ratio of ammonium to 2* sulfate, RN/2S ~ 0.8
to 0.9) with approximately 70% of total ammonia and ammonium (NH x ) in the
particle. Southeastern Aerosol Research and Characterization Network (SEARCH) gas
and aerosol and Southern Oxidant and Aerosol Study (SOAS) Monitor for AeRosols
and Gases in Ambient air (MARGA) aerosol measurements were consistent with these
conditions. CMAQv5.2 regional chemical transport model predictions did not
reflect these conditions due to a factor of 3 overestimate of the nonvolatile
cations. In addition, gas-phase ammonia was overestimated in the CMAQ model
leading to an even lower fraction of total ammonia in the particle. Chemical
Speciation Network (CSN) and aerosol mass spectrometer (AMS) measurements
indicated less ammonium per sulfate than SEARCH and MARGA measurements and were
inconsistent with thermodynamic model predictions. Organic compounds were
predicted to be present to some extent in the same phase as inorganic
constituents, modifying their activity and resulting in a decrease in [H+]air (H+
in MUgm-3 air), increase in ammonia partitioning to the gas phase, and increase
in pH compared to complete organic vs. inorganic liquid-liquid phase separation.
In addition, accounting for nonideal mixing modified the pH such that a fully
interactive inorganic-organic system had a pH roughly 0.7 units higher than
predicted using traditional methods (pH = 1.5 vs. 0.7). Particle-phase
interactions of organic and inorganic compounds were found to increase
partitioning towards the particle phase (vs. gas phase) for highly oxygenated (O
: C>=0.6) compounds including several isoprene-derived tracers as well as levoglu
cosan but decrease particle-phase partitioning for low O: C, monoterpene-derived
species.
PMID- 29963079
TI - Southeast Atmosphere Studies: learning from model-observation syntheses.
AB - Concentrations of atmospheric trace species in the United States have changed
dramatically over the past several decades in response to pollution control
strategies, shifts in domestic energy policy and economics, and economic
development (and resulting emission changes) elsewhere in the world. Reliable
projections of the future atmosphere require models to not only accurately
describe current atmospheric concentrations, but to do so by representing
chemical, physical and biological processes with conceptual and quantitative
fidelity. Only through incorporation of the processes controlling emissions and
chemical mechanisms that represent the key transformations among reactive
molecules can models reliably project the impacts of future policy, energy and
climate scenarios. Efforts to properly identify and implement the fundamental and
controlling mechanisms in atmospheric models benefit from intensive observation
periods, during which collocated measurements of diverse, speciated chemicals in
both the gas and condensed phases are obtained. The Southeast Atmosphere Studies
(SAS, including SENEX, SOAS, NOMADSS and SEAC4RS) conducted during the summer of
2013 provided an unprecedented opportunity for the atmospheric modeling community
to come together to evaluate, diagnose and improve the representation of
fundamental climate and air quality processes in models of varying temporal and
spatial scales. This paper is aimed at discussing progress in evaluating,
diagnosing and improving air quality and climate modeling using comparisons to
SAS observations as a guide to thinking about improvements to mechanisms and
parameterizations in models. The effort focused primarily on model representation
of fundamental atmospheric processes that are essential to the formation of
ozone, secondary organic aerosol (SOA) and other trace species in the
troposphere, with the ultimate goal of understanding the radiative impacts of
these species in the southeast and elsewhere. Here we address questions
surrounding four key themes: gas-phase chemistry, aerosol chemistry, regional
climate and chemistry interactions, and natural and anthropogenic emissions. We
expect this review to serve as a guidance for future modeling efforts.
PMID- 29963080
TI - Malaria Vaccine Development: The Need for Novel Approaches: A Review Article.
AB - Background: Although rigorous efforts have substantially decreased the malaria
burden through decades, it still threatens the lives of millions of children.
Development of an effective vaccine can provide important approach in malaria
control strategies. Unfortunately, development of an effective vaccine for
falciparum malaria has been hindered by the extreme complexity of malaria
parasite biology, complex and diverse parasite genomes, and immune evasion by the
parasites as well as the intricate nature of the parasites infection cycle. The
aim of this review was to discuss the different approaches to malaria vaccine
development until now. Methods: Scientific databases, including MEDLINE (via
PubMed) and SCOPUS were searched up to 30 Jan 2017 and the articles regarding
malaria vaccine development were taken into examination. Results: Several
strategies for malaria vaccine development including pre-erythrocytic vaccines,
antibody-based subunit vaccines, vectored vaccines, whole sporozoite vaccines,
genetically Attenuated parasites and sporozoite subunit vaccine, erythrocytic
vaccines, sexual stage vaccine, transmission-blocking vaccine as well as
synthetic peptides and conjugate vaccine has been introduced. However, the
success has been limited thus far. Conclusion: Although development of malaria
vaccine over the past 70 year has been continued, the discovery, development, and
licensing of a malaria vaccine formulation, which meets safety, affordability,
accessibility, applicability, and efficacy has not yet been achieved.
PMID- 29963081
TI - Immunoprophylactic Potential of a Cocktail of Three Low Molecular Weight Antigens
of Leishmania donovani along with Various Adjuvants Against Experimental Visceral
leishmaniasis.
AB - Background: Currently, there is no vaccine available for any form of
leishmaniasis for human use, including visceral leishmaniasis (VL). The treatment
relies on drugs associated with severe toxic side effects and increased parasite
drug resistance. At present, there is a strong need to develop and implement a
successful vaccine against this disease. Therefore, we evaluated
immunoprophylactic potential of a cocktail of low molecular weight antigens along
with various adjuvants. Methods: The three antigens (2015, Department of Zoology,
Panjab University, Chandigarh), 31kDa, 36 kDa and 51 kDa of L. donovani were used
in this study. Inbred BALB/c mice were immunized with 10 MUg of cocktail antigens
i.e. 31+36+51kDa alone and along with different adjuvants (ALD, saponin, and
liposome). Mice were boosted twice at an interval of 2 wk and after last dose;
mice were given challenge infection with 107 promastigotes. Mice have
sacrificed15 d post immunization and on 30, 60, 90 post-challenge days for
evaluation of different parameters. Results: Immunized animals showed reduced
parasite load, increased DTH responses and elevated levels of IgG2a antibody. The
levels of Th1 cytokines were higher as compared to Th2 cytokines in immunized
animals. Conclusion: Best results were obtained with cocktail of
31+36+51+liposome and this combination conferred maximum protection.
PMID- 29963082
TI - Synchronous Identification of Entamoeba histolytica, Giardia intestinalis, and
Cryptosporidium spp. in Stool Samples Using a Multiplex PCR Assay.
AB - Background: Diarrheal disease annually causes 760000 deaths in children, and 1700
million new cases are reported each year worldwide. Among the parasites,
Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium spp. are the
most important infectious agents leading to diarrhea. Clinical presentations due
to these parasites are more or less similar, and microscopy is not as much as
sensitive for the detection. The aim of this study was to set up and evaluate a
Multiplex PCR Assay for Synchronous Identification of Entamoeba histolytica,
Giardia intestinalis, and Cryptosporidium spp. in Stool Samples. Methods: Samples
were obtained from different sources such as culture media and patient stool
samples. Primer pairs were designed using primer-BLAST, and for the extraction of
DNA, the QIAamp DNA stool mini kit was used. The study was conducted in Tehran,
Iran and completed in 2016. Results: The current multiplex PCR assay for the
detection of E. histolytica achieved sensitivity and specificity of 86.36% (95%
CI: 65.09% to 97.09) and 95.74 % (95% CI: 85.46% to 99.48%), respectively.
Sensitivity and specificity of the test for G. intestinalis was 90.91% (95% CI:
70.84% to 98.88%) and 95.74% (95%CI: 85.46% to 99.48%), respectively, and for the
detection of Cryptosporidium, multiplex PCR showed a sensitivity of 90.91% (95%
CI: 70.84% to 98.88%) and specificity of 95.74% (95%CI: 85.46% to 99.48%).
Conclusion: Multiplex PCR in this study showed admissible sensitivity and
specificity for the detection of E. histolytica, G. intestinalis, and
Cryptosporidium spp. in fecal samples.
PMID- 29963083
TI - Monitoring the Response of Plasmodium vivax to Chloroquine and Uncomplicated P.
falciparum to Artesunate-fansidar Antimalarials in Southeastern Iran.
AB - Background: For many years, malaria was a major life-threatening parasitic
infection in Iran. Although malaria elimination program is implementing in the
country, still some cases annually are reported from malaria-endemic areas.
Methods: This study was conducted in five malaria endemic districts of Sistan and
Baluchistan Province, southeastern Iran, neighboring Afghanistan and Pakistan
countries. Overall, 170 and 38 vivax malaria and falciparum malaria infected
patients were enrolled in the study from 2013-2014. All the cases were selected
according to criteria of the WHO guideline for in vivo drug sensitivity tests in
malaria parasites. Evaluation of drug sensitivity test was conducted with some
modifications. Results: The patients with vivax malaria responded to the regimen
of chloroquine in 37.4(+/-15.9), 40(+/-13.8) and 42(+/-17.7) h for Pakistani,
Iranian and Afghani nationalities respectively based on MPCT evaluation. The
results showed a considerable difference between them and Iranian subjects. MPCT
for the patients with falciparum malaria was calculated as 28(+/-18.05), 26(+/
12.03) and 36(+/-16.9) h for Iranian, Pakistani and Afghani nationalities
respectively. There was a marginally significant difference between Afghani and
other nationalities and between males and females. Conclusion: Treatment of all
the patients resulted in ACPR and MPCT of P. vivax showed that the parasite
became more sensitive to chloroquine than previous years in studied areas.
PMID- 29963085
TI - Phylogenetic Analysis of C Type Lectin from Toxocara canis Infective Larvae and
Comparison with the C Type Lectin Family in the Immune System of Mouse and Human.
AB - Background: C type lectin (CTL) family is a type of calcium-dependent proteins
found in vertebrates and invertebrates. The objective of this study was to
perform a comparative analysis and phylogenetic inferring for understanding the
similarities and differences of carbohydrate recognition domain (CRD) domain of
Toxocara canis CTL and other nematodes, and similar C type lectin involved in the
immune system of mouse and human as their host. Methods: The female T. canis was
retrieved from the 2-6 months puppies (Department of Parasitology, Faculty of
Veterinary Medicine, University of Tehran, 2015). To collect T. canis eggs, the
worms were cultured for 5 d until they were embryonated. The hatching process was
accelerated for collecting the stage 2 larvae, and the larvae were cultured for a
week. A cDNA library was made from the total mRNA of T. canis infective larvae.
The PCR amplification for C type lectin gene was performed and the amino acids
were analyzed using the alignment method and the construction of phylogenetic
tree. Results: The suspension sample maintained at 30 oC for four weeks could
embryonate 90%-100% of eggs. T. canis CTL gene was 657 bp in length and encoded a
protein with 219 amino acids. The CTL of species of Strongylida order were
closely placed in the tree, whereas the members of Ascaridida orders were located
in a separate branch. High levels of similarity (36%-44%) and conservation of C
type lectin from T. canis with mouse and human C type lectins. Its C type lectin
showed a higher similarity with asialoglycoprotein receptor (ASGPR), macrophage
lectin, dendritic cell-specific intercellular adhesion molecule 3-grabbing
nonintegrin (DC-SIGN), MINCLE receptor of mouse and human. Conclusion: Analysis
of CRD domain of C type lectin protein could make a better understanding of their
role in the interaction of nematode parasite with their hosts.
PMID- 29963084
TI - Identification of Antigenic and Immunogenic Proteins of Toxoplasma gondii in
Human and Sheep by Immunoproteomics.
AB - Background: Toxoplasmosis is a parasitic disease caused by the intracellular
protozoan parasite, Toxoplasma gondii, which can infect humans and warm-blooded
animals. This infection can lead to still birth and abortion among some
susceptible hosts especially sheep and human in pregnancy. Development of a
vaccine against T. gondii infection is very important-especially for use in
immunocompromised patients, pregnant women, and sheep. Different antigens of T.
gondii can be potential candidates for immunization. The aims of this study were
to identify the immunodominant and antigenic proteins of T. gondii in sheep and
man. Methods: Tachyzoites' proteins were separated by two-dimensional
polyacrylamide gel electrophoresis (2-DE), and subjected to western blot analysis
probed with T. gondii positive sera of sheep and human (Biotechnology Department
of Pasteur Institute of Tehran, Iran, from April 2016 to March 2017). Finally,
the immunoreactive proteins were identified by mass spectrometry (MALDI-TOF/MS
and MS/MS) technique. Results: Five immunoreactive and antigenic proteins were
recognized by Toxoplasma positive sera of human and sheep. These identified
proteins were Enolase 2, rhoptry protein 4 (ROP4), dense granular protein 14
(GRA14), rhoptry protein 15 (ROP15) and rhoptry protein 9 (ROP9). Conclusion: The
identified immunodominant proteins have potential to be used as diagnostic
antigens and as diagnostic markers of Toxoplasma infection in sheep and human.
PMID- 29963086
TI - Incidence of Antenatal Trichomoniasis and Evaluation of Its Role as a Cause of
Preterm Birth in Pregnant Women Referring to Minia University Hospital, Egypt.
AB - Background: We aimed to determine the incidence of trichomoniasis and its risk
factors in Egyptian pregnant women attending the Minia Maternity and Pediatric
University Hospital, Minia, Egypt and evaluate its association with preterm
birth. Methods: The study was carried out from Aug 2014 to Jun 2015 through 2
phases, the first phase was case-control study, and the second phase was follow
up with intervention. Overall, 300 pregnant women with gestational age of 20-36
weeks with no medical risk factors of preterm labour birth were enrolled. Vaginal
swabs were examined by the wet mount microscopy and culture while urine samples
were examined by urine analysis. Demographic information was collected. Pregnant
women were divided into two groups, study group (with trichomoniasis) and control
group (without trichomoniasis). Positive cases were subjected to metronidazole
treatment. Results: Thirty-five cases were positive for T. vaginalis infection.
Maximum cases were detected by culture (11.7%) followed by wet mount microscopy
(9.7%) whereas least number of cases (7.3%) was detected by urine examination.
Nineteen (54.28%) cases had preterm delivery. Post-delivery adverse outcomes were
observed in 29 cases (82.8%). The high rate of infection was observed in age
group of 20-30 years (P<0.05). In addition, there was a significant T. vaginalis
infection in pregnant women living in rural area, of low socioeconomic and
primary educational levels (P<0.05). Conclusion: Pregnant women lived in rural
area with a low socioeconomic and primary educational levels should be screened
for trichomoniasis to reduce the incidence of preterm delivery and low birth
weight.
PMID- 29963087
TI - Canine Visceral Leishmaniasis; A Seroepidemiological Survey in Jiroft District,
Southern Kerman Province, Southeastern Iran in 2015.
AB - Background: Domestic dogs have been implicated as the main reservoir host of
Mediterranean type of visceral leishmaniasis (VL) that is endemic in some parts
of Iran. This study was performed about role of dogs in canine VL (CVL)
epidemiology in Jiroft District, south of Kerman Province, southeastern Iran.
Methods: Totally, 165 dogs including 100 stray and 65 sheepdogs were randomly
selected. After complete clinical examination blood sample was taken from each
dog. All the collected samples were examined following the serum separation by
direct agglutination test (DAT) for detection of anti-Leishmania infantum
antibodies. The titers of >=1:320 were defined as positive. Results: Overall, of
165 serum samples, 13 samples (7.9%) were positive by DAT at titers of >=1:320.
The seroprevalence was 11% among the stray dogs and 3% among the sheepdogs. There
was no significant difference between stray and sheepdogs in CVL infection. The
highest seroprevalence rate (14.3%) was found in seven-year old dogs. Conclusion:
The present finding indicates the role of stray and sheepdogs in CVL epidemiology
in this area. Further investigations are needed to evaluate the status of VL
infection in human subjects in this area.
PMID- 29963088
TI - Induction of Apoptosis by Alcoholic Extract of Combination Verbascum thapsus and
Ginger officinale on Iranian Isolate of Trichomonas vaginalis.
AB - Background: The protozoan Trichomonas vaginalis is a sexually transmitted disease
(STD). Metronidazole is a chosen drug for the treatment. This study evaluated the
anti trichomonal activity of alcoholic extracts of combination Verbascum thapsus
and Ginger officinale. Methods: This experimental study was conducted in the
Parasitology Laboratory, Kashan University of Medical Sciences, Kashan, Iran in
2015, on 23 women with suspected trichomoniasis referring to Kashan clinical
centers. Medium TYI-S-33 was used for culture of three T. vaginalis isolates.
Different concentrations (25, 50, 100, 200, 400, 800 MUg/ml) of V. thapsus and G.
officinale ethanol extract added to Trichomonas trophozoites in 48-well plates
and metronidazole considered as positive control and the negative control was TYI
S33 containing Trichomonas trophozoites without any drug. In all of mentioned
groups, trophozoites number counted 12, 24, 48 h after culture. Results were
analyzed using ANOVA statistical test, to evaluate the toxicity of extract,
measured by MTT assay. Induced apoptosis of T. vaginalis after treatment with
different concentrations of extract was determined by Flow Cytometry. Results:
IC50 of alcoholic extract of combination V. thapsus and G. officinale and
metronidazole after 24h was 73.80 MUg/ml and 0.0326 MUg/ml, respectively. The
toxicity percentage of 25-800 MUg/ml concentrations of this combination were
between 0.2-1.98. In different concentrations of extract (25,50,100,200 and 400
MUg/ml) apoptosis percent after 48h was 18.97 to 77.19 and necrosis percent was
calculated 1.35, 3.18, 3.10, 1.16 and 4.09, respectively. Conclusion: Alcoholic
extract of combination V. thapsus and G. officinale induces programmed death in
T. vaginalis. Due to no toxicity on macrophages, it can be examined in vivo
studies.
PMID- 29963089
TI - Comparative Functional Study of Thioester-containing Related Proteins in the
Recently Sequenced Genome of Biomphalaria glabrata.
AB - Background: There is paucity of information on functional relationship and
characterization of Biomphalaria glabrata thioester-containing proteins (BgTEP)
to other well-annotated homologues. We performed functional characterization
studies of BgTEP to homologues in Anopheles gambiae and in disparate
invertebrates. Methods: Genomic sequences of TEPs were retrieved after annotation
of the B. glabrata genome. In addition, TEP sequences deposited in NCBI protein
database were also retrieved and utilized for sequence analysis. BgTEP
relatedness to its other homologues as well as functional domain and protein
protein interaction analysis was performed. Results: Our analysis resulted in the
identification of TEPs in a number of organisms including, B. glabrata, A.
gambiae, and Chlamys farreri. In addition, we identified 19 TEP sequences spread
across 10 animal species. The B. glabrata genome contains 14190 unannotated
proteins after filtration with about 85% of its proteome annotated. The
phylogenetics, functional domain and protein-protein interaction analyses suggest
an immunological role for BgTEP in B. glabrata. Conclusion: The predicted role of
thioester-containing proteins to be involved in immunological role in B. glabrata
may have a strong effect on resistance to infection.
PMID- 29963090
TI - Trypanocidal Effects of Cisplatin alone and in Combination with Nigella sativa
Oil on Experimentally Infected Mice with Trypanosoma evansi.
AB - Background: Due to the limited number of the available drugs for the treatment of
trypanosomiasis, this study was designed to evaluate the trypanocidal effects of
cisplatin or/and Nigella sativa oil (NSO) in experimentally infected mice with T.
evansi. Methods: During 2015 at the Parasitology Department, Menoufia University,
Menoufia, Egypt, sixty Swiss albino mice were divided into six groups: normal
control (I), infected control (II); cisplatin-treated (III); NSO-treated (IV);
combined cisplatin + NSO-treated (V) and diminazene-treated (VI). The tested
drugs were evaluated by the assessment of parasitaemia, measurement of aspartate
aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, serum
IgM and a histopathological study. Results: NSO showed a trypanocidal effect,
however; it was not as effective as cisplatin or diminazene. There were
significant increases of AST, ALT, urea, and creatinine in group II and III,
which were significantly reduced in cisplatin + NSO-treated group (V). Moreover,
there were significant reductions in serum IgM and the pathological changes of
the examined organs of group V when they were compared with other treated groups.
Conclusion: Cisplatin combined with NSO showed a trypanocidal effect against T.
evansi with preservation of vital organs functions and architecture.
PMID- 29963091
TI - Additional Glance on the Role of Dientamoeba fragilis & Blastocystis hominis in
Patients with Irritable Bowel Syndrome.
AB - Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal
disease with high population prevalence. Dientamoeba fragilis and Blastocystis
hominis are reported worldwide as a cause of human gastrointestinal symptoms.
This study evaluated the possible link between this syndrome and the infection
with D. fragilis and B. hominis in Egypt. Methods: Overall, 310 stool samples
(160 from IBS patients and 150 from controls) were obtained from Tropical
Medicine Outpatient Clinic, Faculty of Medicine, Ain Shams University, Cairo,
Egypt between Mar 2015 and Feb 2016. All the stool specimens underwent direct
examination and Trichrome staining. Each sample was cultivated on Jones and
Robinson's media. Results: Overall, 42 cases (28%) showed B. hominis and 2 cases
(1.3%) for D. fragilis infections. After performing the culture methods for B.
hominis and D. fragilis, detections increased to 50 cases (33.3%) and 3 cases
(2%), respectively. While among 150 controls 18 (12%) positive samples were
detected as B. hominis. Conclusion: There may be a possible relationship between
the presentation of irritable bowel syndrome and D. fragilis and B. hominis
infections, which have to be excluded first.
PMID- 29963092
TI - The Prevalence of Trichomoniasis in Women Referred to Clinical Centers in South
of Tehran, Iran during 2015-2016.
AB - Background: This study aimed to estimate the prevalence of trichomoniasis
infection among females in Tehran, Iran. Methods: This study was conducted on 482
women referred to the 6 obstetrics and gynecology centers of Tehran during 2015
2016. Some information including education, occupation, and number of sexual
partners was obtained and clinical signs and symptoms of the genital tract were
diagnosed by clinical examination. Two swabs were collected from the posterior
fornix of patients. Two laboratory techniques, wet mount, and culture were
carried out. Finally, statistical analysis test was performed using SPSS software
version 16.0. Results: Age distribution of patients was 15-60 yr. Trichomonas
vaginalis was detected in 2 out of 482 participants (0.41%). All of the infected
individuals were married (0.43%) and they had unique sexual partner and all of
them had clinical symptoms. Significant association was observed between
incidence of T. vaginalis infection and educational levels (P= 0.03), occupation
(P=0.006), clinical symptoms (P=0.001), marriage (P=0.006) and bacterial
infection (P=0.018). Conclusion: The prevalence of trichomoniasis was low and its
incidence was associated with several risk factors.
PMID- 29963093
TI - Epidemiology and Molecular Prevalence of Toxoplasma gondii in Cattle Slaughtered
in Zahedan and Zabol Districts, South East of Iran.
AB - Background: Toxoplasma gondii is an obligate, intracellular parasite which causes
the toxoplasmosis in humans and warm-blooded animals. Red meat is an important
source for transmission of the infection to humans. This study aimed to determine
the prevalence of Toxoplasma among imported and indigenous cattle in the Sistan
region. Methods: One hundred samples from slaughtered cattle were collected from
two abattoirs of Zabol and Zahedan, South East of Iran in 2015. Each sample was a
mixture of three muscle, including tongue, cardiac, and triceps. Additional data
of each cattle, including sex, breed, age, indigenous or imported, location of
slaughter, management practices, and feeding system were obtained through
observations and interviews. Infection by T. gondii was determined by PCR method.
Results: The prevalence of Toxoplasma in indigenous cattle was 6% and in imported
cattle was 26%, and this difference was statistically significant (P=0.006).
Moreover, the prevalence of Toxoplasma was statistically associated with
management practices (P=0.01) and feeding system (P=0.001). However, relationship
between the prevalence of Toxoplasma with age, breed, sex, and location of
slaughter was not statistically significant. Conclusion: Since the prevalence of
Toxoplasma among imported cattle is higher than indigenous cattle, so strict
supervision for importing livestock from neighboring countries is necessary.
PMID- 29963094
TI - Genetic Characterization of Hydatid Cysts Isolated from Domestic Animals in
Lorestan Province, Western Iran.
AB - Background: Regarding hydatid cyst (cystic echinococcosis, CE) as a human public
health problem in the West of Iran, molecular data related to the genotypes of
Echinococcus granulosus in cattle and sheep in these regions are still
insufficient. Here, we evaluated the genotypes of E. granulosus infecting sheep
and cattle in western Iran. Methods: Totally, 36 hydatid cysts including 18
hydatid cysts of sheep and 18 hydatid cysts of cattle were collected from
Khorramabad slaughterhouse (Lorestan Province), Western Iran between May to
September 2014. Protoscoleces or germinal layers were collected from individual
cysts, DNA was extracted, and genotyping was performed by sequencing and
analyzing mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Results: In
sequencing analysis, all of sheep isolates belonged to genotype G1 (sheep
strain). Among cattle hydatid cyst isolates, 16/18 (88.9%) were belonged to
genotype G1 and 2/18 (11.1%) were belonged to G3 genotype. The phylogenetic
analysis showed two clusters; one of the clusters includes cattle G3 genotype and
the other cluster represents sheep and cattle G1 genotype that were isolated.
Conclusion: The common sheep strain/G1 is predominant genotype in the western
part of Iran, followed by G3 genotype, circulating among the animal hosts in this
region. Further studies covering a larger number of isolates might be necessary
to see if there are other genotypes in the hydatid cyst population in this region
of Iran.
PMID- 29963095
TI - Comparative Study of Wheatley's Trichrome Stain and In-vitro Culture against PCR
Assay for the Diagnosis of Blastocystis sp. in Stool Samples.
AB - Background: This study evaluated the performance of routine permanent stain and
cultivation method in comparison with polymerase chain reaction assay as the
reference technique to detect Blastocystis sp. Methods: A cross-sectional study
was conducted among aboriginal populations that reside in Pahang, Peninsular
Malaysia in Feb to Mar 2015. A total of 359 stool samples were examined using
Wheatley's trichrome stain, in-vitro cultivation in Jones' medium and PCR assay.
Positive amplicons were subjected to sequencing and phylogenetic analysis.
Results: Fifty-six (15.6%) samples were detected positive with Blastocystis sp.
by Wheatley's trichrome stain and 73 (20.3%) by in-vitro culture, while PCR assay
detected 71 (19.8%) positive samples. Detection rate of Blastocystis sp. was
highest in combination of microscopic techniques (27.9%). The sensitivity and
specificity of Wheatley's trichrome staining and in-vitro culture techniques
compared to PCR assay were 49.3% (95% CI: 37.2-61.4) and 92.7% (95% CI: 89.1
95.4) and 39.4% (95% CI: 28.0-51.8) and 84.4% (95% CI: 79.7-88.4), respectively.
However, the sensitivity [60.6% (95% CI: 48.3-71.9)] of the method increased when
both microscopic techniques were performed together. False negative results
produced by microscopic techniques were associated with subtype 3. The agreement
between Wheatley's trichrome stain, in-vitro culture and combination of
microscopic techniques with PCR assay were statistically significant by Kappa
statistics (Wheatley's trichrome stain: K = 0.456, P<0.001; in-vitro culture: K =
0.236, P<0.001 and combination techniques: K = 0.353, P<0.001). Conclusion: The
combination of microscopic technique is highly recommended to be used as a
screening method for the diagnosis of Blastocystis infection either for clinical
or epidemiological study to ensure better and accurate diagnosis.
PMID- 29963096
TI - A Preliminary Survey on Gastrointestinal Parasites of Domestic Ducks in Ahvaz,
Southwest Iran.
AB - Background: Despite ducks being birds resistant to infection, the favorable
habitat of ducks such as subtropical climate or stagnant water is also a perfect
place for survival of the parasites. Methods: This study was conducted from Dec
2014 to Apr 2015 to determine the prevalence of gastrointestinal parasites of
domestic ducks in Ahvaz and environs, southwest of Iran. Overall, 41 fresh fecal
samples were collected and prepared using formol-ether concentration, modified
Ziehl-Neelsen, sheather's floatation and zinc sulfate sedimentation methods.
Light microscopic morphometry was used for identification of helminth eggs and
oocysts. Results: 60.97% of ducks were infected with three different nematodes
and/or four protozoan parasites. The identified nematodes were Capillaria sp.,
(50%) Subulura spp. (16.66%) and Echinuria spp. (33.33%). The protozoan oocystes
were Cryptosporidium spp. (50%) and coccidian species (%58.33) and included
Wenionella philiplevinei, Tyzerria spp. and Isospora. mandari. Mixed infection
with two or more parasites was common. Twenty (80%) had single, four (16%) double
and one (4%) triple infection. Conclusion: This is the first report of coccidian
infection in domestic ducks of Iran. Further studies will be necessary on
epidemiology and pathogenicity of the parasitic infections in ducks of this area.
PMID- 29963097
TI - Brain Parenchyma (pons) Involvement by Visceral Leishmaniasis: A Case Report.
AB - Leishmaniasis, as a vector-borne disease, is transmitted by sandfly and caused by
Leishmania protozoa. Brain involvement rarely occurs in visceral leishmaniasis.
In this paper, a rare case of pons involvement by visceral leishmaniasis (VL) is
reported. A 54 yr old man from Southwest of Iran (Yasuj) presented to the
Emergency Ward with a 3-wk history of headache (continuous, throbbing, and
general), fever, chills, weakness, anorexia, and weight loss.
PMID- 29963098
TI - Molecular Evaluation of a Case of Fasciola hepatica in Wild Boar in Southwestern
Iran: A Case Report.
AB - Wild boars may be infected with several zoonotic parasitic infections including
Fasciola spp. We reported a case of Fasciola infection in a wild boar in Bushehr
Province in southwestern Iran. The sample was isolated from the liver of a hunted
wild boar. A few of adult worms were fixed and stained. DNA was extracted from
apical and lateral parts of the worms and PCR amplified, targeting NADH
dehydrogenase subunit 1 (nad1) and cytochrome C oxidase subunit 1 (cox1)
mitochondrion genes. Although the worm was quite long and looked much similar to
F. gigantica, sequencing and analysis of PCR products of nad1 and cox1 genes
revealed that the isolate has the most similarity with F. hepatica. This is the
first report of molecular evaluation of Fasciola spp. from wild boar in Iran.
PMID- 29963099
TI - An Atypical Presentation of Disseminated Mucocutaneous Leishmaniasis Caused by
Leishmania major In Iran.
AB - Although leishmaniasis is an endemic disease in Iran the mucosal involvement is
rare. Mucocutaneous leishmaniasis (MCL) mainly caused by Leishmanial braziliensis
infection, reported with other Leishmania species such as L. major. Herein a 78
yr old man with MCL from Iran is presented who referred to Razi Hospital
Dermatology Clinic, Tehran, Iran, for multiple ulcerative lesions on mid face
skin, mucosa of upper lip and anterior fossa of nose, dorsal aspect of the hands
and the posterior aspect of heels. Skin biopsy revealed necrotizing and
granulomatous tissue pattern that suggested infection pathogenesis but the smear
for leishmaniasis, Mycobacterium spp, and fungal elements was negative at first.
In order to a positive PPD test, he was treated by anti-tuberculosis treatment. A
month after starting drugs for tuberculosis, the prepared microscopical smears
were positive for Leishman bodies this time. The skin biopsy revealed amastigote
forms of Leishmania sp. and the PCR assay on specimens of lesions proved L. major
as the principal pathogenic agent. There was good response to systemic treatment
with meglumine antimoniate (Glucantime(r)) 3 gr per day until one week followed
by 4.5 gr per day for another week. We forced to discontinue of drug because of
cardiac toxicity at the end of 2nd wk of treatment.
PMID- 29963100
TI - Esophageal perforation in children: etiology and management, with special
reference to endoscopic esophageal perforation.
AB - Perforation of the esophagus is an uncommon problem with significant morbidity
and mortality. In children undergoing endoscopy, the risk of perforation is
higher when interventional endoscopy is performed. The clinical features depend
upon the site of esophageal perforation. Opinions vary regarding the optimal
treatment protocol, and the role of conservative management in this context is
not well established. Esophageal perforation that occurs as a consequence of
endoscopy in children requires careful evaluation and management, as outlined in
this article.
PMID- 29963101
TI - Clinical and laboratory profiles of hospitalized children with acute respiratory
virus infection.
AB - Purpose: Despite the availability of molecular methods, identification of the
causative virus in children with acute respiratory infections (ARIs) has proven
difficult as the same viruses are often detected in asymptomatic children.
Methods: Multiplex reverse transcription polymerase chain reaction assays were
performed to detect 15 common respiratory viruses in children under 15 years of
age who were hospitalized with ARI between January 2013 and December 2015. Viral
epidemiology and clinical profiles of single virus infections were evaluated.
Results: Of 3,505 patients, viruses were identified in 2,424 (69.1%), with the
assay revealing a single virus in 1,747 cases (49.8%). While major pathogens in
single virus-positive cases differed according to age, human rhinovirus (hRV) was
common in patients of all ages. Respiratory syncytial virus (RSV), influenza
virus (IF), and human metapneumovirus (hMPV) were found to be seasonal pathogens,
appearing from fall through winter and spring, whereas hRV and adenovirus (AdV)
were detected in every season. Patients with ARIs caused by RSV and hRV were
frequently afebrile and more commonly had wheezing compared with patients with
other viral ARIs. Neutrophil-dominant inflammation was observed in ARIs caused by
IF, AdV, and hRV, whereas lymphocyte-dominant inflammation was observed with RSV
A, parainfluenza virus, and hMPV. Monocytosis was common with RSV and AdV,
whereas eosinophilia was observed with hRV. Conclusion: In combination with viral
identification, recognition of virus-specific clinical and laboratory patterns
will expand our understanding of the epidemiology of viral ARIs and help us to
establish more efficient therapeutic and preventive strategies.
PMID- 29963102
TI - The outcome of percutaneous stent implantation in congenital heart disease:
experience of a single institute.
AB - Purpose: The efficacy of percutaneous stent implantation for congenital heart
disease (CHD) in Korea, where stent availability is limited, has not been
determined. This study evaluated the acute and midterm results of stent
implantation in different CHD subgroups. Methods: Stents were implanted in 75
patients with 81 lesions: (1) pulmonary artery stenosis (PAS) group, 56 lesions
in 51 patients; (2) coarctation of the aorta (CoA) group, 5 lesions in 5
patients; (3) Fontan group, 13 lesions in 12 patients; (4) ductal stent group, 3
lesions in 3 patients; and (5) other CHD group, 4 lesions in 4 patients. Mean
follow-up duration was 2.1 years (0.1-4 years). Medical records were reviewed
retrospectively. Results: The minimum lumen diameter (MLD) in PAS and CoA
increased from 5.0+/-1.9 mm and 8.4+/-1.6 mm to 10.1+/-3.6 mm and 12.3+/-2.5 mm,
respectively (P<0.01). In the PAS group, pressure gradient decreased from 25.7+/
15.6 mmHg to 10.4+/-10.1 mmHg, and right ventricular to aortic pressure ratio
from 0.56+/-0.21 to 0.46+/-0.19. In the CoA group, the pressure gradient
decreased from 50+/-33 mmHg to 17+/-8 mmHg. In the ductal stent group, the MLD of
the ductus increased from 2.3 mm to 4.3 mm and arterial oxygen saturation from
40%-70% to 90%. No deaths were associated with stent implantation. Stent
migration occurred in 3 patients, but repositioning was successful in all. Stent
redilation was performed successfully in 26 cases after 29+/-12 months.
Conclusion: Percutaneous stent implantation was safe and effective, with
acceptable short and mid-term outcomes in Korean CHD patients.
PMID- 29963103
TI - Outcome of ultrasonographic imaging in infants with sacral dimple.
AB - Purpose: Sacral dimples are a common cutaneous anomaly in infants. Spine
ultrasonography (USG) is an effective and safe screening tool for patients with a
sacral dimple. The aim of this study was to determine the clinical manifestations
in patients with an isolated sacral dimple and to review the management of spinal
cord abnormalities identified with USG. Methods: We reviewed clinical records and
collected data on admissions for a sacral dimple from March 2014 through February
2017 that were evaluated with spine USG by a pediatric radiologist. During the
same period, patients who were admitted for other complaints, but were found to
have a sacral dimple were also included. Results: This study included 230 infants
under 6-months-old (130 males and 100 females; mean age 52.8+/-42.6 days). Thirty
one infants with a sacral dimple had an echogenic filum terminale, and 57
children had a filar cyst. Twenty-seven patients had a low-lying spinal cord, and
only one patient was suspected of having a tethered cord. Follow-up spine USG was
performed in 28 patients, which showed normalization or insignificant change.
Conclusion: In this study, all but one infant with a sacral dimple had benign
imaging findings. USG can be recommended in infants with a sacral dimple for its
convenience and safety.
PMID- 29963104
TI - Breast abscess caused by Staphylococcus aureus in 2 adolescent girls with atopic
dermatitis.
AB - Atopic dermatitis (AD) is a chronic inflammatory skin disease in children.
Patients with AD experience a high rate of colonization of the skin surface by
Staphylococcus aureus. Because of a skin barrier defect, there is a potential
risk of staphylococcal invasive infection in patients with AD. Here, we present 2
cases of breast abscess caused by S. aureus in 2 adolescent girls with severe AD.
Methicillin-sensitive S. aureus was identified from the breast abscess material.
They were treated with appropriate antibiotics, however surgical drainage of the
abscess was needed in case 1. Identical strains were found from the breast
abscess material as well as the lesional and the nonlesional skin of the patients
through matrixassisted laser desorption/ionization time-of-flight analysis. We
characterized the differential abundance of Firmicutes phylum in patients' skin
in microbiota analysis. In particular, S. aureus, a member of Firmicutes,
differed significantly between the lesional and the normal-appearing skin. Our
cases demonstrate the potential severity of bacterial deep tissue infection in AD
and the dysbiosis of skin microbiota may be involved in inflammation in AD.
PMID- 29963105
TI - Knockdown of Chloride Channel-3 Inhibits Breast Cancer Growth In Vitro and In
Vivo.
AB - Purpose: Chloride channel-3 (ClC-3) is a member of the chloride channel family
and plays a critical role in a variety of cellular activities. The aim of the
present study is to explore the molecular mechanisms underlying the antitumor
effect of silencing ClC-3 in breast cancer. Methods: Human breast cancer cell
lines MDA-MB-231 and MCF-7 were used in the experiments. Messenger RNA and
protein expression were examined by quantitative real-time polymerase chain
reaction and western blot analysis. Cell proliferation was measured by the
bromodeoxyuridine method, and the cell cycle was evaluated using fluorescence
activated cell sorting. Protein interaction in cells was analyzed by co
immunoprecipitation. Tumor tissues were stained with hematoxylin-eosin and tumor
burden was measured using the Metamorph software. Results: Breast cancer tissues
collected from patients showed an increase in ClC-3 expression. Knockdown of ClC
3 inhibited the secretion of insulin-like growth factor (IGF)-1, cell
proliferation, and G1/S transition in breast cancer cells. In the mouse xenograft
model of human breast carcinoma, tumor growth was significantly slower in animals
injected with ClC-3-deficient cells compared with the growth of normal human
breast cancer cells. In addition, silencing of ClC-3 attenuated the expression of
proliferating cell nuclear antigen, Ki-67, cyclin D1, and cyclin E, as well as
the activation of extracellular signalregulated protein kinases (ERK) 1/2, both
in vitro and in vivo. Conclusion: Together, our data suggest that upregulation of
ClC-3 by IGF-1 contributes to cell proliferation and tumor growth in breast
cancer, and ClC-3 deficiency suppresses cell proliferation and tumor growth via
the IGF/IGF receptor/ERK pathway.
PMID- 29963106
TI - Histone Deacetylase-3 Modification of MicroRNA-31 Promotes Cell Proliferation and
Aerobic Glycolysis in Breast Cancer and Is Predictive of Poor Prognosis.
AB - Purpose: The incidence and mortality of breast cancer is increasing worldwide.
There is a constant quest to understand the underlying molecular biology of
breast cancer so as to plan better treatment options. The purpose of the current
study was to characterize the expression of histone deacetylases-3 (HDAC3), a
member of class I HDACs, and assess the clinical significance of HDAC3 in breast
cancer. Methods: Quantitative real-time polymerase chain reaction,
immunohistochemistry, and western blot analysis were used to examine messenger
RNA and protein expression levels. The relationships between HDAC3 expression and
clinicopathological variables were analyzed. MTT assays were used to detect cell
proliferation. Glucose-uptake, lactate, adenosine triphosphate, and lactate
dehydrogenase assays were employed to detect aerobic glycolysis. Chromatin
immunoprecipitation was used to detect microRNA-31 (miR-31) promoter binding.
Results: Our data revealed that HDAC3 was upregulated in breast cancer tissue
compared with matched para-carcinoma tissues, and high levels of HDAC3 were
positively correlated with advanced TNM stage and N stage of cancer. Furthermore,
overexpression of HDAC3 promoted breast cancer cell-proliferation and aerobic
glycolysis. The functional involvement of HDAC3 was related in part to the
repression of miR-31 transcription via decreased histone H3 acetylation at lysine
K9 levels of the miR-31 promoter. Survival analysis revealed that the level of
HDAC3 was an independent prognostic factor for breast cancer patients.
Conclusion: Our findings revealed that HDAC3 served as an oncogene that could
promote cell proliferation and aerobic glycolysis and was predictive of a poor
prognosis in breast cancer. HDAC3 participated in the cell proliferation of
breast cancer, which may prove to be a pivotal epigenetic target against this
devastating disease.
PMID- 29963107
TI - Lymphocyte-Activation Gene-3 Expression and Prognostic Value in Neoadjuvant
Treated Triple-Negative Breast Cancer.
AB - Purpose: In this study, we aimed to evaluate lymphocyte-activation gene-3 (LAG-3)
expression and its prognostic value in neoadjuvant-treated triple-negative breast
cancer (TNBC). Methods: LAG-3, programmed death-1 (PD-1), programmed death ligand
1 (PD-L1), and CD8+ tumor-infiltrating lymphocyte (TILs) levels were examined
using immunohistochemistry in 148 preand 114 post-neoadjuvant chemotherapy (NACT)
specimens of human TNBC tissue. Correlations between expression levels and
clinicopathological features were analyzed. Prognostic values for combined
detection in TNBC following NACT were evaluated. Results: In pre-NACT specimens,
LAG-3 expression showed a significant association with pathological complete
response (pCR, p=0.038) and was correlated with PD-1 (p<0.001) and PD-L1
(p=0.008). In post-NACT specimens, high expression of LAG-3 showed significant
effects on nodal status (p=0.023) and PD-1 (p<0.001). The expression of immune
markers on TILs significantly increased following NACT. Multivariate analysis
indicated that only nodal status (odds ratio [OR], 0.226; 95% confidence interval
[CI], 0.079-0.644; p=0.005) and high quantities of CD8+TILs (OR, 3.186; 95% CI,
1.314-7.721; p=0.010) are independent predictors of pCR. Nodal status (hazard
ratio [HR], 2.666; 95% CI, 1.271-5.594; p=0.010), CD8+TILs (HR, 0.313; 95% CI,
0.139-0.705; p=0.005), and the LAG-3-high/PD-L1-high group (HR, 2.829; 95% CI,
1.050-7.623; p=0.040) provided prognostic values for patients with TNBC following
NACT. Conclusion: CD8+TILs were sensitive predictive markers in response to NACT.
High expression of LAG-3 in residual tissues, especially in combination with PD
L1, was associated with poor prognosis.
PMID- 29963108
TI - Association between Changes in Serum 25-Hydroxyvitamin D Levels and Survival in
Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy.
AB - Purpose: We investigated the changes in serum 25-hydroxyvitamin D (25[OH]D)
levels before and after neoadjuvant chemotherapy (NCT) and the associations with
pathologic complete response (pCR) and survival in patients with breast cancer.
Methods: Serum 25(OH)D concentrations were measured pre- and post-NCT in 374
patients between 2010 and 2013. Based on a cutoff of 20 ng/mL, patients were
categorized into "either sufficient" or "both deficient" groups. The associations
with clinicopathological data, including pCR and survival, were analyzed using
multivariable analyses. Results: Patients with either pre- or post-NCT sufficient
25(OH)D levels accounted for 23.8%, and the overall pCR rate was 25.9%. Most
patients showed 25(OH)D deficiency at diagnosis and 65.8% showed decreased serum
levels after NCT. Changes in 25(OH)D status were associated with postmenopause
status, rural residence, baseline summer examination, and molecular phenotype,
but not pCR. No association between survival and 25(OH)D status was found,
including in the subgroup analyses based on molecular phenotypes. Conclusion:
Most Korean patients with breast cancer showed vitamin D deficiency at diagnosis
and a significant decrease in the serum concentration after NCT. No association
with oncologic outcomes was found. Therefore, although optimal management for
vitamin D deficiency is urgent for skeletal health, further research is warranted
to clearly determine the prognostic role of vitamin D in patients with breast
cancer who are candidates for NCT.
PMID- 29963109
TI - Combined Let-7a and H19 Signature: A Prognostic Index of Progression-Free
Survival in Primary Breast Cancer Patients.
AB - Purpose: The long non-coding RNA H19, a conservatively imprinted gene, acts as a
molecular sponge for the let-7 family, which has been identified as a set of
tumor suppressors. However, the combined prognostic value of H19 and let-7a
signature in breast cancer patients remains unclear. Methods: In this research we
assessed the prognostic value of the combined H19 and let-7a signature in breast
cancer patients by retrospectively reviewing that data of 79 patients who
underwent neoadjuvant chemotherapy; we also investigated the expression and
function of H19 in breast cancer cell lines in vitro. Survival data were
calculated using the Kaplan-Meier method and compared using the log-rank test.
Univariate and multivariate survival analyses were conducted using the Cox
proportional hazards regression method. As determined using X-tile, the optimal
cutoff value for the risk score to assess progression-free survival (PFS) based
on the combined signature was -0.1. Results: Patients with an overall positive
treatment response had higher let-7a and lower H19 levels. In addition, let-7a
expression was negatively correlated with H19 expression. Patients with a risk
score of >-0.1 had shorter overall survival and PFS. In vitro data showed that
chemoresistant cell lines exhibit higher H19 and lower let-7a levels and
knockdown H19 restores paclitaxel sensitivity. Conclusion: Our results suggest
that the combined let-7a and H19 signature is a novel prognostic factor for
breast cancer patients treated with neoadjuvant chemotherapy.
PMID- 29963110
TI - Efficiency of Cytokine-Induced Killer Cells in Combination with Chemotherapy for
Triple-Negative Breast Cancer.
AB - Purpose: The treatment of triple-negative breast cancer (TNBC) remains
challenging, due to the absence of estrogen, progesterone, and human epidermal
growth factor receptors. This study was designed to evaluate the efficiency and
safety of cytokine-induced killer (CIK) cell immunotherapy, following regular
chemotherapy, for patients with TNBC. Methods: A total of 340 patients with
postmastectomy TNBC, from January 1, 2010 to June 30, 2014, were included in this
retrospective study. Seventy-seven patients received CIK cell immunotherapy,
following regular chemotherapy (arm 1), and 263 patients received regular
chemotherapy alone (arm 2). The primary aim was overall survival (OS) and disease
free survival (DFS), and the treatment responses and adverse events were also
evaluated. Results: The 5-year DFS and OS rates in arm 1 were 77.9% and 94.3%,
compared with 69.8% and 85.6% in arm 2, respectively (p=0.159 and p=0.035,
respectively). This clearly shows that there was no statistical difference in the
5-year DFS between the two groups. Multivariate analyses of arm 1 indicated that
a Karnofsky performance score (KPS) >=90 and stage I/IIA disease were
significantly associated with a prolonged DFS period (hazard ratio [HR], 0.25;
95% confidence interval [CI], 0.09-0.74; p=0.012; and HR 0.21; 95% CI, 0.06-0.82;
p=0.024, respectively), but a KPS >=90 and stage I/IIA disease were not
independent prognostic factors for OS. Toxicity was mild in patients who received
the CIK therapy. Conclusion: The data suggested that CIK cell immunotherapy
improved the efficiency of regular chemotherapy in patients with TNBC, and the
side effects of CIK cell immunotherapy were mild.
PMID- 29963111
TI - Interactions between Alcohol Consumption and Adjuvant Hormone Therapy in Relation
to Breast Cancer-Free Survival.
AB - Purpose: Alcohol consumption is associated with an increase in breast cancer
risk, but findings on the association of alcohol with survival after breast
cancer diagnosis have been inconsistent. Further, whether these associations
could differ by adjuvant hormone therapy status is unknown. We examined
interactions between alcohol consumption and adjuvant hormone therapy in relation
to breast cancer-free survival among women with a primary breast cancer
diagnosis. Methods: Participants in this study included 1,399 women diagnosed
with primary breast cancer between 2007 and 2012 at the Moffitt Cancer Center.
Alcohol consumption during the year preceding diagnosis was assessed in a patient
survey. Information on tumor characteristics, breast cancer treatment and
outcomes was available from the Moffitt Cancer Registry. Associations were
examined using Cox proportional hazards models in stratified analyses by adjuvant
hormone therapy status, after adjustment for potential confounders. Results:
Overall, alcohol consumption was associated with significantly improved breast
cancer-free survival (any vs. none: hazard ratio [HR], 0.77; 95% confidence
interval [CI], 0.65-0.92). Among women without adjuvant hormone therapy, alcohol
consumption was associated with better survival in heavy drinkers (HR, 0.63; 95%
CI, 0.43-0.93). Among women with adjuvant hormone therapy, survival was better in
women consuming alcohol as compared to nondrinkers (moderate: HR, 0.69, 95% CI,
0.51-0.93; heavy: HR, 0.74, 95% CI, 0.57-0.96; any: HR, 0.71, 95% CI, 0.57-0.87).
There was no significant interaction between alcohol and adjuvant hormone therapy
(p-interaction=0.54 for alcohol modeled as none or any and p=0.34 for alcohol
modeled as none, moderate, and heavy). Conclusion: Associations of alcohol
consumption with breast cancer-free survival are similar in women with and
without adjuvant hormone therapy. Future studies are warranted to elucidate
potential mechanisms underlying the observed inverse associations.
PMID- 29963112
TI - Genetic Variants Associated with Clinicopathological Profiles in Sporadic Breast
Cancer in Sri Lankan Women.
AB - Purpose: Several single nucleotide polymorphisms (SNPs) have been reported to be
associated with clinicopathological profiles in sporadic breast cancer based on
studies conducted on major population groups. The knowledge of the effects of
these common genetic variants in South Asian populations remains limited. The
present study aimed to investigate the association between a selected set of SNPs
and the clinicopathological profiles in sporadic breast cancer in Sri Lankan
women. Methods: A total of 350 postmenopausal women with histologically confirmed
invasive breast cancer were genotyped for 58 SNPs located in 36 breast cancer
related genes. The clinicopathological factors that were investigated included
age of onset, tumor histologic grade, and lymph node involvement, as well as
estrogen receptor (ER), progesterone receptor, and human epidermal growth factor
receptor 2 (HER2) status. Association testing was performed using logistic
regression models adjusted for confounding factors. Results: Seven SNPs showed
significant associations with clinicopathological profiles in breast cancer. The
G allele of BRCA1:rs799917 (p=0.047; beta [standard error; SE]=-1.069 [0.537])
and the G allele of NQO2:rs17136117 (p=0.040, beta [SE]=1.901 [0.923]) were found
to be associated with age of onset between 50 and 59 years. The C allele of
CDH1:rs13689 (odds ratio [OR], 2.121; p=0.033) was found to be associated with ER
positive breast cancer. The A allele of AKT1:rs1130214 (OR, 2.095; p=0.011) and
the C allele of NQO2:rs2071002 (OR, 1.632; p=0.045) were associated with HER2
positive breast cancer. The C allele of BRCA2:rs15869 (OR, 1.600; p=0.041) and
the C allele of CCND1:rs7177 (OR, 1.555; p=0.041) were associated with high tumor
histologic grade. Conclusion: The common genetic variants identified in the AKT1,
BRCA1, BRCA2, CCND1, CDH1, and NQO2 genes could serve as potential clinical and
prognostic biomarkers in sporadic breast cancer patients. Further studies are
required to validate our current findings in other populations.
PMID- 29963113
TI - Prognostic Validation of the American Joint Committee on Cancer 8th Staging
System in 24,014 Korean Patients with Breast Cancer.
AB - Purpose: The American Joint Committee on Cancer (AJCC) recently released the
breast cancer staging system, 8th edition, which included additional four
biologic factors. However, there has been no external validation of the
prognostic value of the new stages with different population-based databases.
Methods: To validate the prognostic value of the new staging system in the Asian
population, with a focus on Korean patients with breast cancer, we performed a
retrospective study with data from the Korean Breast Cancer Society that included
24,014 patients with invasive ductal or lobular carcinoma who underwent surgery
between January 2009 and January 2012 in Korea. The proportional differences were
evaluated between the anatomic staging system (AJCC 7th edition) and the
prognostic staging system (AJCC 8th edition, December 2017 published version).
Comparisons of overall survival (OS) and disease-free survival (DFS) with Kaplan
Meier graphs and hazard ratios were also performed. Results: Our analysis
included 24,014 patients (median age, 50 years; range, 20-91 years). Stage I, II,
and III disease accounted for 47.6%, 43.5%, and 8.9%, respectively, of anatomic
stages and 61.8%, 27.6%, and 10.8%, respectively, of clinical prognostic stages.
A total of 6,272 cases (26.1%) were upstaged, 4,656 (19.4%) were downstaged, and
13,086 (54.5%) remained unchanged. OS and DFS decreased in the order from
prognostic stages IA to IIIC but did not change among the anatomic stage groups.
Conclusion: Our data suggests that the prognostic staging system provides
superior prognostic value to the anatomic staging system in Korean patients with
breast cancer.
PMID- 29963115
TI - Ex Vivo Shear-Wave Elastography of Axillary Lymph Nodes to Predict Nodal
Metastasis in Patients with Primary Breast Cancer.
AB - Purpose: There is still a clinical need to easily evaluate the metastatic status
of lymph nodes during breast cancer surgery. We hypothesized that ex vivo shear
wave elastography (SWE) would predict precisely the presence of metastasis in the
excised lymph nodes. Methods: A total of 63 patients who underwent breast cancer
surgery were prospectively enrolled in this study from May 2014 to April 2015.
The excised axillary lymph nodes were examined using ex vivo SWE. Metastatic
status was confirmed based on the final histopathological diagnosis of the
permanent section. Lymph node characteristics and elasticity values measured by
ex vivo SWE were assessed for possible association with nodal metastasis.
Results: A total of 274 lymph nodes, harvested from 63 patients, were examined
using ex vivo SWE. The data obtained from 228 of these nodes from 55 patients
were included in the analysis. Results showed that 187 lymph nodes (82.0%) were
nonmetastatic and 41 lymph nodes (18.0%) were metastatic. There was significant
difference between metastatic and nonmetastatic nodes with respect to the mean
(45.4 kPa and 17.7 kPa, p<0.001) and maximum (55.3 kPa and 23.2 kPa, p<0.001)
stiffness. The elasticity ratio was higher in the metastatic nodes (4.36 and
1.57, p<0.001). Metastatic nodes were significantly larger than nonmetastatic
nodes (mean size, 10.5 mm and 7.5 mm, p<0.001). The size of metastatic nodes and
nodal stiffness were correlated (correlation coefficient of mean stiffness,
r=0.553). The area under curve of mean stiffness, maximum stiffness, and
elasticity ratio were 0.794, 0.802, and 0.831, respectively. Conclusion: Ex vivo
SWE may be a feasible method to predict axillary lymph node metastasis
intraoperatively in patients undergoing breast cancer surgery.
PMID- 29963114
TI - Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients
Receiving Letrozole as an Early Adjuvant Treatment.
AB - Purpose: There are few reports from Asian countries about the long-term results
of aromatase inhibitor adjuvant treatment for breast cancer. This observational
study aimed to evaluate the long-term effects of letrozole in postmenopausal
Korean women with operable breast cancer. Methods: Self-reported quality of life
(QoL) scores were serially assessed for 3 years during adjuvant letrozole
treatment using the Korean version of the Functional Assessment of Cancer Therapy
Breast questionnaires (version 3). Changes in bone mineral density (BMD) and
serum cholesterol levels were also examined. Results: All 897 patients received
the documented informed consent form and completed a baseline questionnaire
before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects,
and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer,
respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and
36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The
dropout rate was 16.5%. The serial trial outcome index, the sum of the physical
and functional well-being subscales, increased gradually and significantly from
baseline during letrozole treatment (p<0.001). The mean serum cholesterol level
increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD
significantly decreased from -0.39 at baseline to -0.87 after 36 months
(p<0.001). Conclusion: QoL gradually improved during letrozole treatment. BMD and
serum cholesterol level changes were similar to those in Western countries,
indicating that adjuvant letrozole treatment is well tolerated in Korean women,
with minimal ethnic variation.
PMID- 29963116
TI - Microinvasive Carcinoma versus Ductal Carcinoma In Situ: A Comparison of
Clinicopathological Features and Clinical Outcomes.
AB - Purpose: Although microinvasive carcinoma is distinct from ductal carcinoma in
situ (DCIS), the clinical significance of microinvasion in DCIS remains elusive.
The purpose of this study is to evaluate the clinicopathological features and
clinical outcomes of microinvasive carcinoma compared with pure DCIS. Methods: We
assessed 613 cases of DCIS and microinvasive carcinoma that were consecutively
resected from 2003 to 2014 and analyzed clinicopathological variables, expression
of standard biomarkers such as the estrogen receptor (ER), progesterone receptor
(PR), human epidermal growth factor receptor 2 (HER2), p53, and Ki-67, and tumor
recurrence. Results: Among the 613 cases, 136 (22.2%) were classified as
microinvasive carcinoma. Microinvasive carcinoma was significantly associated
with DCIS with a large extent, high nuclear grade, necrosis, and comedotype
architectural pattern. ER and PR expressions were dominantly observed in pure
DCIS, whereas positive HER2 status, p53 overexpression, and high Ki-67
proliferation indices were more frequently observed in microinvasive carcinoma.
Lymph node metastasis was found in only four cases of microinvasive carcinoma
with multifocal microinvasion. In the multivariate analysis, DCIS with a large
extent, comedo-type architectural pattern, and negative ER status were found to
be independent predictors of microinvasion. During follow-up, 12 patients had
ipsilateral breast recurrence, and no differences in recurrence rates were
observed between patients with DCIS and those with microinvasive carcinoma. The
triple-negative subtype was the only factor that was associated with tumor
recurrence. Conclusion: Microinvasive carcinomas are distinct from DCIS in terms
of clinicopathological features and biomarker expressions but are similar to DCIS
in terms of clinical outcomes. Our results suggest that microinvasive carcinoma
can be treated and followed up as pure DCIS.
PMID- 29963117
TI - Which Patients with Left Breast Cancer Should be Candidates for Heart-Sparing
Radiotherapy?
AB - Purpose: This study aimed to identify risk factors that have significant
interaction with radiation exposure to the heart, and thus to determine
candidates for heart-sparing radiotherapy (RT) among women with left breast
cancer. Methods: We identified 4,333 patients who received adjuvant RT following
breast-conserving surgery for ductal carcinoma in situ or invasive breast cancer
from 1996 to 2010. Incidence rates of cardiovascular disease were compared
between left-sided and right-sided RT, and stratified by age and risk factors
such as body mass index (BMI), smoking, hyperlipidemia, hypertension, diabetes,
administration of anthracycline, and trastuzumab. Results: In all patients, the
cumulative incidence of cardiovascular disease was greater in patients treated
with left-sided RT than in those treated with right-sided RT, but the difference
was not significant (p=0.428). Smoking (hazard ratio [HR], 5.991; 95% confidence
interval [CI], 2.109-17.022; p=0.002) and hyperlipidemia (HR, 5.567; 95% CI,
3.235-9.580; p<0.001) were the most powerful risk factors for cardiovascular
disease. There was no significant factor that further increased the risk of
cardiovascular disease after left breast RT compared to right breast RT.
Conclusion: Although hyperlipidemia and smoking are risk factors for
cardiovascular disease, they have not been proven to increase the risk of RT
related cardiovascular disease in Korean women.
PMID- 29963118
TI - Comparison of Outcomes between Direct-to-Implant Breast Reconstruction Following
Nipple-Sparing Mastectomy through Inframammary Fold Incision versus
Noninframammary Fold Incision.
AB - Purpose: In properly selected patients with breast cancer, nipple-sparing
mastectomy (NSM) is generally considered safe by oncologic standards. We examined
two groups of patients who underwent direct-to-implant (DTI) reconstruction after
NSM, comparing complications encountered, revision rates, and aesthetic outcomes.
The patients were stratified based on type of surgical incision and assigned to
inframammary fold (IMF) and non-IMF groups. Methods: We investigated 141 patients
(145 breasts) subjected to NSM and immediate DTI reconstruction between 2013 and
2016. A total of 62 breasts (in 58 patients) were surgically removed via IMF
incisions, with the other 83 breasts (in 83 patients) removed by non-IMF means.
Results: Complications associated with IMF (n=62) and non-IMF (n=83) incisions
were as follows: skin necrosis (IMF, 9; non-IMF, 18); hematoma (IMF, 3; non-IMF,
4); seroma (IMF, 8; non-IMF, 4); mild capsular contracture (IMF, 4; non-IMF, 7);
and tumor recurrence (IMF, 2; non-IMF, 8). Surgical revisions were counted as
duplicates (IMF, 18; non-IMF, 38). Aesthetic outcomes following IMF incisions
were rated as very good (44.2%), good (23.1%), fair (23.1%), or poor (9.6%).
Conclusion: IMF incision enables complete preservation of the nipple-areolar
complex, yielding superior aesthetic results in immediate DTI breast
reconstruction after NSM. The nature of incision used had no significant impact
on postoperative complications or reoperation rates and had comparable oncologic
safety to that of non-IMF incisions. IMF incisions produced the least visible
scarring and did not affect breast shape. Most patients were satisfied with the
aesthetic outcomes.
PMID- 29963120
TI - Apocrine Encapsulated Papillary Carcinoma of the Breast: The First Reported Case
with an Infiltrative Component.
AB - Apocrine encapsulated papillary carcinoma (EPC) of the breast is a rare neoplasm,
and only 10 cases have been reported in the literature to date. Although EPC by
definition lacks a peripheral myoepithelial layer, all previously published
apocrine EPC cases were clinically indolent and lacked a conventional invasive
component. Herein, we report the 11th case of apocrine EPC, which had a
conventional invasive carcinoma component and provides evidence of the malignant
potential of this entity. We postulate that apocrine EPC is most likely a
morphological variant of conventional EPC, with the same unpredictable malignant
potential as non-apocrine cases.
PMID- 29963119
TI - Verification of a Western Nomogram for Predicting Oncotype DXTM Recurrence Scores
in Korean Patients with Breast Cancer.
AB - A recent study conducted at the University of Tennessee Medical Center using a
large dataset from the National Cancer Database (NCDB) reported the use of
nomograms for predicting Oncotype DXTM (ODX) scores with clinicopathologic data.
We reviewed the data of 218 patients who underwent the ODX test at a single
institution in Korea to confirm that nomograms can accurately predict ODX score
groups using our data, which differ from those of the NCDB in terms of ethnicity.
The concordance index (c-index) of nomograms was much lower than that of the
University of Tennessee Medical Center for high- and low-risk groups of
commercial ODX and Trial Assigning Individualized Options for Treatment values.
Although the nomogram for predicting ODX scores was based on a large dataset, it
could not be generalized to patients in Asia. Further studies using large
datasets of patients from different ethnicities should be performed to develop a
nomogram applicable to patients worldwide.
PMID- 29963121
TI - Erratum: Associations between Dietary Allium Vegetables and Risk of Breast
Cancer: A Hospital-Based Matched Case-Control Study.
AB - [This corrects the article on p. 292 in vol. 19, PMID: 27721879.].
PMID- 29963122
TI - Erratum: Development of a Nomogram to Predict N2 or N3 Stage in T1-2 Invasive
Breast Cancer Patients with No Palpable Lymphadenopathy.
AB - [This corrects the article on p. 270 in vol. 20, PMID: 28970853.].
PMID- 29963123
TI - Erratum to: Minimally Invasive Surgical Mitral Valve Repair: State of the Art
Review.
AB - [This corrects the article on p. 14 in vol. 13, PMID: 29593831.].
PMID- 29963124
TI - SB431542 inhibited cigarette smoke extract induced invasiveness of A549 cells via
the TGF-beta1/Smad2/MMP3 pathway.
AB - Lung cancer has high morbidity and mortality rates. Smoking is involved in the
pathogenesis of lung cancer, and tobacco smoke may increase tumor cell invasion
and metastasis. The effects of cigarette smoke extract (CSE) on the carcinoma
human alveolar basal epithelial A549 cell line were investigated. A549 cells were
exposed to increasing concentrations of CSE for 12, 24 and 48 h, and the
transforming growth factor-beta1 (TGF-beta1) signal pathway was inhibited by
addition of SB431542, a TGF-beta1 receptor antagonist. The proliferation of A549
cells was assayed by a Cell Counting kit-8, invasiveness was assayed using
Transwell chambers, and TGF-beta1, phosphorylated mothers against decapentaplegic
homolog 2 (p-Smad2), and matrix metalloproteinase 3 (MMP3) levels was assessed by
western blot analysis. The invasiveness of A549 cells and the expression of TGF
beta1, pSmad2, and MMP-3 were significantly increased by CSE (P<0.05). The
effects of CSE were abrogated by SB431542 (P<0.05). In conclusion, CSE increased
the invasiveness of A549 cells and its effects were abrogated by SB431542 and the
TGF-beta1/Smad2/MMP-3 pathway may have been involved.
PMID- 29963125
TI - Effects of microRNA-20a on the proliferation, migration and apoptosis of multiple
myeloma via the PTEN/PI3K/AKT signaling pathway.
AB - Multiple myeloma (MM) is a heterogeneous disease with a poor prognosis.
Circulating microRNAs (miRNAs) have shown potential as non-invasive prognostic
biomarkers for heterogeneous diseases. miR-20a has been shown involved in various
human cancers, and the phosphatase and tensin homolog/phosphoinositide 3
kinase/protein kinase B (PTEN/P13K/Akt) signaling pathway plays a key role in
cell proliferation, migration and apoptosis. Here, we investigated the effect of
miR-20a on the PTEN/PI3K/Akt signaling pathway during MM cell proliferation,
migration and apoptosis. Reverse transcription quantitative polymerase chain
reaction was applied to detect miR-20a expression in plasma from 30 MM patients
and MM cell lines. CCK-8 assays, Transwell assays, Annexin V/PI double-staining
and western blotting were performed to examine the protein expressions of PTEN,
PI3K and Akt during cellullar proliferation, migration, cycling, and apoptosis.
Significant upregulation of miR-20a and deregulation of PTEN were observed in MM
cells. We also identified PTEN as a downstream target gene of miR-20a, which
bound to the 3'-untranslated region of PTEN. Overexpression of miR-20a was
associated with decreased PTEN expression, and treatment with miR-20a inhibitors
decreased cell proliferation, migration and clonogenicity and reduced the protein
expressions of PI3K and p-Akt but increased PTEN protein expression compared with
blank and negative control groups. Taken together, these results showed that
inhibition of miR-20a suppresses MM progression by modulating the PTEN/PI3K/Akt
signaling pathway. These findings suggest that miR-20a may be a novel molecular
therapeutic target for the treatment of MM.
PMID- 29963126
TI - Antitumor mechanisms of bifidobacteria.
AB - Cancer remains one of the most common causes of mortality globally. Chemotherapy,
one of the major treatment strategies for cancer, primarily functions by
targeting the cancer cells and affecting them physiologically, but also affects
normal cells, which is a major concern at present. Therefore, adverse effects of
chemotherapy drugs, including myelosuppression and liver and kidney damage, are
of concern. Now, microbial products have attracted attention in cancer treatment
research. Notably, carcinogenesis is considered to be associated with microbial
dysbiosis, particularly the positive antitumor effects of bifidobacteria.
Although there remains a substantial amount to be understood about the regulation
of bifidobacteria, bifidobacteria remain an attractive and novel source of cancer
therapeutics. The present review focuses on introducing the latest information on
the antitumor effects of bifidobacteria and to propose future strategies for
using bifidobacteria in the development of cancer therapeutics.
PMID- 29963127
TI - Knockdown of B7H6 inhibits tumor progression in triple-negative breast cancer.
AB - The B7 family, the most common family of secondary signaling molecules, consists
of eight cell-surface proteins, which regulate the T-cell mediated immune
response by delivering co-inhibitory or co-stimulatory signals through their
corresponding ligands. Among them, natural killer cell cytotoxicity receptor 3
ligand 1 (NCR3LG1, also known as B7H6) has been reported as a new member, and is
involved in tumor progression of various types of human cancer. However, the role
of B7H6 in triple-negative breast cancer (TNBC) remains unknown. In the present
study, western blotting was performed to determine the protein expression levels
of B7H6 in a normal mammary epithelial cell line (MCF-10A), non-TNBC breast
cancer cell lines (MCF-7 and AU565) and TNBC cell lines (MDA-MB-231 and MDA-MB
468). B7H6 was knocked down using small interfering RNA, and an MTT assay was
performed to determine proliferation ability, flow cytometry was used to analyze
apoptosis, and Transwell and wound-healing assays were performed to measure
migration ability. Expression of proliferation-associated proteins (SMAD family
member 4 and beta-catenin) and apoptosis-associated proteins (BCL2 associated X,
BCL2 apoptosis regulator and caspase-3) were analyzed by western blotting. The
results demonstrated that B7H6 was highly expressed in TNBC cells, and that
knockdown of B7H6 inhibited cell proliferation and migration, and promoted
apoptosis. Furthermore, the results revealed that proliferation and apoptosis
associated proteins were altered in the B7H6-knockdown MDA-MB-231 cells. In
conclusion, the present study demonstrated that B7H6 may have significant roles
in the regulation of cell proliferation, apoptosis and migration of TNBC cells.
PMID- 29963128
TI - Carbon nanoparticles guide contralateral central neck dissection in patients with
papillary thyroid cancer.
AB - The treatment of contralateral central neck lymph node metastasis is
controversial in patients with papillary thyroid cancer. The present study
reports the use of carbon nanoparticles (CNs) as lymph node tracers and discusses
the potential role of predicting contralateral central neck metastasis is
evaluated, so as to guide contralateral central neck dissection (CND). A total of
70 consecutive patients with papillary thyroid cancer were enrolled in the
present study. All patients underwent a total or near-total thyroidectomy plus
bilateral CND, during which CNs were used as a lymph node tracer. Of the 70
enrolled patients, 51 (72.86%) were confirmed to have lymph node metastasis in
the central neck, 50 (71.43%) patients in the ipsilateral central neck and 14
(20.00%) in the contralateral central neck. A total of 579 (84.90%) lymph nodes
were stained black by CNs. Of the 193 metastatic lymph nodes, 168 were located in
the ipsilateral central compartment and the other 25 in the contralateral central
compartment. A total of 147 (76.17%) metastatic lymph nodes were stained black. A
total of 21 metastatic lymph nodes were found in the contralateral central
compartment, 4 metastatic lymph nodes of contralateral central compartment were
not black-stained. The sensitivity and specificity of CNs for contralateral
metastasis was 84 and 25%, respectively. Contralateral central lymph node
metastasis was significantly associated with extrathyroid extension and the
presence of ipsilateral central neck lymph node metastasis. Together, the results
of the present study reveal that CNs might accurately predict contralateral
central lymph nodes metastasis and could be used to direct CND.
PMID- 29963129
TI - Expression of engrailed homeobox 2 regulates the proliferation, migration and
invasion of non-small cell lung cancer cells.
AB - The present study aimed to investigate the expression, biological function and
mechanism of action of engrailed homeobox 2 (EN2) in non-small cell lung cancer
(NSCLC) at the tissue and cellular level. A total of 42 patients who underwent
surgical resection of NSCLC tissues between January 2014 and January 2015 were
included in the present study. EN2 mRNA expression levels in explanted NSCLC
tissues were determined using reverse-transcription quantitative polymerase chain
reaction analysis. Adenocarcinoma human alveolar basal epithelial A549 cells were
transfected with negative control plasmids or those containing EN2, enabling its
overexpression. To assess the effect of EN2 overexpression in A549 cells, a Cell
Counting kit-8 assay was used to analyze cellular proliferation, a Transwell
assay was used to evaluate cellular migration and invasion and flow cytometry was
used to detect the cell cycle distribution. To measure protein expression of EN2
and beta-catenin in A549 cells, western blotting was also conducted. EN2 mRNA
expression levels in NSCLC tissues were lower than those in normal tissues, and
were associated with metastasis, clinical staging and differentiation degrees of
NSCLC. Increased expression of EN2 inhibited the proliferation of A549 cells in
vitro, and suppressed their migration and invasion. Elevated EN2 expression
inhibited the proliferation of A549 cells by regulating the G1/S phase
transition. beta-catenin protein expression levels and nuclear translocation in
A549 cells were inhibited by EN2 overexpression. The present study demonstrated
that expression of EN2 in NSCLC tissues was downregulated and negatively
associated with the degree of disease differentiation, lymphatic metastasis and
clinical staging. Overexpression of EN2 inhibits the proliferation, migration and
invasion of A549 cells, as well as the expression of beta-Catenin and nuclear
translocation.
PMID- 29963130
TI - Camptothecin inhibits the progression of NPC by regulating TGF-beta-induced
activation of the PI3K/AKT signaling pathway.
AB - Nasopharyngeal carcinoma (NPC) is a type of cancer that is characterized by
increased invasiveness, metastatic potential and tumor recurrence. Camptothecin
has been demonstrated to exhibit anticancer activity. However, the potential
underlying molecular mechanisms mediated by camptothecin in NPC cells remain
elusive. In the present study, the efficacy of camptothecin for NPC was
investigated in vitro and in vivo. Additionally, the potential signaling pathway
mediated by camptothecin in NPC cells was also examined. The results indicated
that the viability and aggressiveness of NPC cells were suppressed by
camptothecin treatment in a dose-dependent manner. Camptothecin administration
downregulated the expression levels of cell-cycle-associated proteins including
cyclin 1, cyclin-dependent kinase (CDK)1 and CDK2 in NPC cells. Expression levels
of migration-associated proteins including vimentin, fibronectin and epithelial
cadherin were regulated by camptothecin treatment in NPC cells. Additionally,
camptothecin inhibited the expression of transforming growth factor-beta (TGF
beta), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), whereas TGF
beta overexpression abrogated camptothecin-mediated inhibition of PI3K and AKT
expression and camptothecin-mediated inhibition of the viability and
aggressiveness of NPC cells. Camptothecin significantly inhibited tumor growth
and increased survival times in a mouse model of cancer. In conclusion, these
results indicate that camptothecin treatment may inhibit the viability of NPC
cells and aggressiveness by regulating the TGF-beta-induced PI3K/AKT signaling
pathways, which in turn may be a potential molecular target for the treatment of
NPC.
PMID- 29963131
TI - MicroRNA-19b promotes the migration and invasion of ovarian cancer cells by
inhibiting the PTEN/AKT signaling pathway.
AB - Local and systemic metastasis is the main reason for the poor survival rate of
patients with ovarian cancer (OC). MicroRNAs (miRNAs/miRs) are short non-coding
RNAs that serve critical roles in the initiation and progression of OC. The
present study demonstrated that expression of miR-19b was significantly increased
in OC tissues and cell lines. Analysis of clinicopathological features revealed
that the increased expression of miR-19b was associated with advanced
International Federation of Gynecology and Obstetrics stage and lymphatic
metastasis of OC patients. Loss-of-function experiments demonstrated that the
silencing of miR-19b reduced the migration and invasion of OVCAR-3 cells;
contrarily, the overexpression of miR-19b facilitated the migration and invasion
of CAOV-3 cells. Furthermore, miR-19b regulated the expression of phosphatase and
tensin homolog (PTEN) and the activity of the PTEN/RAC serine/threonine-protein
kinase pathway in vitro. Notably, the results of dual-luciferase reporter assays
indicated that PTEN was a direct downstream target of miR-19b in OC. Taken
together, the results of the current study demonstrated that miR-19b serves an
oncogenic role in the progression of OC, and could potentially act as a biomarker
and therapeutic target for OC patients.
PMID- 29963132
TI - Nab-paclitaxel is effective against intrahepatic cholangiocarcinoma via
disruption of desmoplastic stroma.
AB - Intrahepatic cholangiocarcinoma (IH-CCA) is the second predominant hepatic
malignancy worldwide. However, effective treatment strategies for IH-CCA have not
yet been developed. Nab-paclitaxel may be an effective drug against IH-CCA, a
type of desmoid-like tumor, and its antitumor effects may be attributable to its
ability to disrupt the cancer-associated fibroblasts. In the present study, MTT
and Annexin-V apoptosis detection kits were used to evaluate the efficacy of
paclitaxel and nab-paclitaxel against human cholangiocarcinoma KKU-100 and KKU
213 cell lines. A rat model of thioacetamide-induced spontaneous desmoplastic IH
CCA was used to compare the treatment response of four different drug regimens:
Control, paclitaxel, nab-paclitaxel and gemcitabine/oxaliplatin. Positron
emission tomography and immunofluorescence analysis were used to measure the
tumor volume and to study the resected tumor, respectively. In vitro, paclitaxel
and nab-paclitaxel induced anti-proliferative effects in KKU-100 and KKU-M213
cells. With regards to the treatment regimes, only nab-paclitaxel and
gemcitabine/oxaliplatin induced antitumor effects in the rat model of
thioacetamide-induced IH-CCA. The immunofluorescence study indicated that nab
paclitaxel was more efficient in disrupting cancer-associated fibroblasts than
paclitaxel. In conclusion, nab-paclitaxel is effective against IH-CCA owing to
its ability to markedly disrupt the desmoplastic stroma.
PMID- 29963133
TI - Interplay between inflammatory tumor microenvironment and cancer stem cells.
AB - Cancer stem cells (CSCs), which have a close connection with tumor
microenvironment, play a pivotal role in tumorigenesis, tumor progression, and
metastasis. The inflammatory microenvironment is an essential component of tumor
microenvironment. In the recent years, many studies have demonstrated that the
inflammatory microenvironment induces the initiation of tumors, and contributes
to the process of the progression of tumors, as well as metastasis. In this
review, we summarize the relationship between CSCs and inflammatory components,
such as inflammatory cytokines (IFNs, TNF, IL-6, IL-17) and inflammatory cells
(myeloid-derived suppressor cells, tumor-associated macrophages). To illuminate
the key factors that exert important actions in the tumor process would be
important to improve the clinical outcome of the treatment for different types of
cancer.
PMID- 29963135
TI - Disabled homolog 2 interactive protein functions as a tumor suppressor in
osteosarcoma cells.
AB - The disabled homolog 2 interactive protein (DAB2IP) gene is a member of the
family of Ras GTPases and functions as a tumor suppressor in many types of
carcinoma; however, its function in osteosarcoma remains unclear. The aim of the
present study was to determine the function of DAB2IP in osteosarcoma and normal
bone cells in vitro. The expression of DAB2IP protein was assessed in osteoblast
and osteosarcoma cell lines by western blot analysis. The effects of DAB2IP
expression on cell proliferation, colony formation, apoptosis, cell cycle, and
cell migration and invasion were evaluated by in vitro studies. DAB2IP expression
was lower in osteosarcoma cell lines than in normal osteoblast cell lines. DAB2IP
expression affected cell proliferation, apoptosis and cell cycle distribution. In
addition, DAB2IP inhibited the migration and invasion of osteosarcoma and normal
osteoblast cells. Therefore, DAB2IP may function as a tumor suppressor in
osteosarcoma cell lines by inhibiting cell proliferation and invasion.
PMID- 29963134
TI - Tumor angiogenesis and anti-angiogenic gene therapy for cancer.
AB - When Folkman first suggested a theory about the association between angiogenesis
and tumor growth in 1971, the hypothesis of targeting angiogenesis to treat
cancer was formed. Since then, various studies conducted across the world have
additionally confirmed the theory of Folkman, and numerous efforts have been made
to explore the possibilities of curing cancer by targeting angiogenesis. Among
them, anti-angiogenic gene therapy has received attention due to its apparent
advantages. Although specific problems remain prior to cancer being fully curable
using anti-angiogenic gene therapy, several methods have been explored, and
progress has been made in pre-clinical and clinical settings over previous
decades. The present review aimed to provide up-to-date information concerning
tumor angiogenesis and gene delivery systems in anti-angiogenic gene therapy,
with a focus on recent developments in the study and application of the most
commonly studied and newly identified anti-angiogenic candidates for anti
angiogenesis gene therapy, including interleukin-12, angiostatin, endostatin,
tumstatin, anti-angiogenic metargidin peptide and endoglin silencing.
PMID- 29963137
TI - Expression of MMP-2 and TIMP-3 with incidence and prognosis of giant-cell tumor
of the bone.
AB - The expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of
matrix metalloproteinase-3 (TIMP-3) in giant-cell tumor of bone (GCT), and the
correlation of their expression with the clinicopathologic features and prognosis
were investigated. A total of 70 GCT patients treated in our hospital from
September, 2013 to September, 2015, were selected, and the tumor and para
carcinoma tissues were obtained by surgery. The expression levels of MMP-2 and
TIMP-3 in GCT and para-carcinoma tissues were detected via semi-quantitative
polymerase chain reaction (PCR) and western blot analysis, as well as
immunohistochemical staining. Moreover, the clinicopathological data of the GCT
patients were collected to study the correlation of MMP-2 and TIMP-3 with
clinicopathological features and prognosis of GCT. The results of semi
quantitative PCR and western blot analysis revealed that the expression level of
MMP-2 in tissues of the 70 GCT patients was significantly higher than that in
para-carcinoma tissues, and the difference was statistically significant
(P<0.01), while the expression level of TIMP-3 was obviously lower than that in
para-carcinoma tissues (P<0.01). The results of immunohistochemical staining
revealed that the positive expression rate of MMP-2 was 57.6% in GCT tissues and
18.9% in para-carcinoma tissues, while that of TIMP-3 was 63.2% in GCT tissues
and 13.8% in para-carcinoma tissues, and the differences were statistically
significant (P<0.01). The expression levels of MMP-2 and TIMP-3 were correlated
with the diameter of tumor, clinical staging, lymph node metastasis and relapse
of GCT (P<0.01), but were not correlated with the age and sex of GCT patients
(P>0.05). There was a negative correlation between MMP-2 and TIMP-3 expression
levels (r=-0.258, P<0.05). The expression levels of MMP-2 and TIMP-3 are closely
related to the clinicopathological features and prognosis of patients, which can
be used as one of the clinical examination indexes of GCT and also provide new
insights for the clinical treatment of GCT.
PMID- 29963136
TI - Downregulation of aquaporin 3 inhibits cellular proliferation, migration and
invasion in the MDA-MB-231 breast cancer cell line.
AB - Aquaporins are membrane proteins that regulate cellular water flow. Recently,
aquaporins have been proposed as mediators of cancer cell biology. A subset of
aquaporins, referred to as aquaglyceroporins are known to facilitate the
transport of glycerol. The present study describes the effect of gene knockdown
of the aquaglyceroporin AQP3 on MDA-MB-231 breast cancer cell proliferation,
migration, invasion, adherence and response to the chemotherapeutic agent 5
fluorouracil. shRNA mediated AQP3 gene knockdown induced a 28% reduction in
cellular proliferation (P<0.01), a 39% decrease in migration (P<0.0001), a 24%
reduction in invasion (P<0.05) and a 25% increase in cell death at 100 uM 5-FU
(P<0.01). Analysis of cell permeability to water and glycerol revealed that MDA
MB-231 cells with knocked down AQP3 demonstrated a modest decrease in water
permeability (17%; P<0.05) but a more marked decrease in glycerol permeability
(77%; P<0.001). These results suggest that AQP3 has a role in multiple aspects of
breast cancer cell pathophysiology and therefore represents a novel target for
therapeutic intervention.
PMID- 29963138
TI - Long noncoding RNA AFAP1-AS1 is upregulated in NSCLC and associated with lymph
node metastasis and poor prognosis.
AB - Long noncoding RNA (lncRNA) has been indicated to have an important role in
various types of malignant tumors; however, only a small number of lncRNAs have
been entirely elucidated. In the present study, a novel lncRNA, actin filament
associated protein 1 antisense RNA 1 (AFAP1-AS1), was investigated, which is
highly expressed in non-small cell lung cancer (NSCLC). Reverse transcription
quantitative polymerase chain reaction and in situ hybridization were performed
to detect AFAP1-AS1 expression in frozen tissues and tissue microarrays,
respectively. The results revealed that the expression level of AFAP1-AS1 was
significantly increased in tumor tissues, compared with the paired non-cancerous
tissues. It was also determined that the AFAP1-AS1 expression level was higher in
patients with lymph node metastasis than those without lymph node metastasis
(P=0.014). Kaplan-Meier analysis was conducted to evaluate the overall survival
of patients with NSCLC and different expression levels of AFAP1-AS1, and the
results indicated that patients with high AFAP1-AS1 expression had a reduced
survival time, compared with those with low AFAP1-AS1 expression (P=0.011). Cox
regression analysis was also performed to analyze the prognostic value of lncRNA
AFAP1-AS1. The obtained data demonstrated that lncRNA AFAP1-AS1 was an
unfavorable prognostic biomarker for NSCLC (HR: 3.12, 95% CI (1.05-9.25),
P=0.040). In conclusion, it was demonstrated that lncRNA AFAP1-AS1 is
overexpressed in NSCLC and an unfavorable biomarker for patients with NSCLC.
PMID- 29963139
TI - miR-142 suppresses proliferation and induces apoptosis of osteosarcoma cells by
upregulating Rb.
AB - It has been reported that microRNA-142 (miR-142) is a tumor suppressor gene. The
present study primarily investigated whether the overexpression of miR-142 was
able to inhibit the proliferation, apoptosis and expression of apoptosis
associated proteins in osteosarcoma (OS) cells. Different concentrations of miR
142 were transfected into the OS MG-63 cell line using Lipofectamine 2000. The
cell lines were divided into three groups: Normal group (non-transfected group),
miR-142 transfected group, and negative group, which were transfected with random
miR-142 fragment. The proliferation of cells was detected by MTT assay. The
expression of miR-142 was detected by reverse transcription-quantitative
polymerase chain reaction (RT-qPCR). DAPI staining was performed to investigate
the influence of miR-142 on the morphology of MG-63c ells. The apoptotic cell
percentages were determined by flow cytometry with Annexin V-fluorescein
isothiocyanate/propidium iodide double staining. Expression of tumor suppressors,
phosphatase and tensin homolog (PTEN) and Retinoblastoma-associated protein (Rb),
and apoptosis-associated proteins were evaluated by western blotting. RT-qPCR
indicated a higher expression of miR-142 in the transfected group (miR-142 was
transfected into the MG-63 cell line) compared with that in the normal (non
transfected group) and negative control groups. The proliferation of miR-142
transfected cells was significantly lower compared with that in the normal and
negative groups. Furthermore, an increased apoptosis rate accompanied by a
statistically significant upregulation of PTEN, Rb phosphorylation, cleaved
caspase-3 and cytochrome c protein levels were detected in the transfected group,
indicating an internal apoptosis pathway was involved in this process.
Furthermore, no significant changes were identified between the normal and
negative groups (P>0.05). The present study demonstrated that miR-142
overexpression by liposomal transfection resulted in an inhibitory effect on MG
63 cell proliferation. The underlying mechanisms may relate to the upregulation
of tumor suppressor and activation of caspase signaling pathway, which may
provide a novel horizon in short nucleotide drugs on the management of OS.
PMID- 29963140
TI - Gastric follicular lymphoma: A report of 3 cases and a review of the literature.
AB - Follicular lymphoma (FL) occurs primarily in the gastrointestinal tract, with the
stomach being one of the rarest sites. According to the literature, <20 cases of
primary gastric FL have been reported, with the number of cases with detailed
pathological descriptions being even less. The aim of the present study was to
compare clinicopathological features of gastric FL with FL at alternative sites.
A total of 3 cases of gastric FL were retrieved from among 3,216 cases in the
databases of 4 university hospitals in South Korea: Seoul National University
(SNU) Hospital, SNU Boramae Hospital, SNU Bundang Hospital (all Seoul, South
Korea) and Dongtan Sacred Heart Hospital Hallym University (Dongtan, South
Korea), including 2 primary cases and 1 case that was possibly secondary to nodal
FL. The 2 primary gastric FL cases were incidentally detected in routine health
check-ups. An endoscopy revealed a single polypoid submucosal mass and biopsies
failed to confirm the diagnosis due to minimal mucosal involvement. Therefore, a
partial gastrectomy was performed. The epicenters of the tumors were submucosal,
with focal extension to the muscularis propria. However, 1 case exhibited an
isolated FL nodule in the omentum. Histopathological examination revealed FL of
grade 1-2 with a follicular pattern and with strong expression of germinal center
markers and B-cell lymphoma 2 (BCL2). Rearrangement of BCL2 was not identified
using fluorescence in situ hybridization studies in 2 cases. In contrast to these
2 cases, the remaining FL case was confirmed with an endoscopic biopsy. The
endoscopy revealed multiple eroded polypoid lesions, and pathology revealed FL of
grade 1-2 with a predominantly diffuse pattern, and with immunoglobulin heavy
chain IGH/BCL2 translocation. In view of the extensive lymphadenopathy, the last
case possibly presented as secondary involvement of nodal FL. It is challenging
to diagnose FL in the stomach due to little mucosal involvement, as well as the
unfamiliarity of the tumor due to its rarity. However, the results of the present
study suggest that primary gastric FL may exhibit unique pathological features,
including a predominantly follicular pattern and an absence of BCL2
rearrangement.
PMID- 29963141
TI - Treatment effect of conversion therapy and its correlation with VEGF expression
in unresectable rectal cancer with liver metastasis.
AB - To investigate the therapeutic effect of conversion therapy and its correlation
with vascular endothelial growth factor (VEGF) expression in unresectable rectal
cancer with liver metastasis. A total of 116 cases of unresectable rectal cancer
patients with liver metastasis were randomly divided into control and observation
group, 58 cases in each group, all of these patients were treated by conversion
therapy, patients in control were treated by FOLFOXIRI treatment program, and in
observation group were treated by FOLFOXIRI program treatment and bevacizumab.
Efficacy and adverse reactions were compared between the two groups, the levels
of VEGF in portal vein and the expression of VEGF in cancer tissue were compared,
after 5 years of follow-up, the prognosis of the two groups were observed.
Objective efficiency and conversion rate of observation was significantly higher
than the control group, survival rate of postoperative observation was
significantly higher than that of control group (P>0.05). There was no
significant difference in adverse reactions between the two groups (P>0.05). The
positive rate of VEGF in portal vein blood and the expression of VEGF in the
observation was significantly lower than that in the control group (P<0.05). The
5-year survival rate of VEGF high expression was significantly lower than that of
VEGF low expression group (P<0.05). FOLFOXIRI combined with bevacizumab in
patients with unresectable hepatic metastasis of rectal cancer can provide higher
conversion rate and hepatectomy opportunities, and reduce VEGF expression in
patients with unresectable rectal cancer, which is closely related to VEGF
expression, therefore it is beneficial to better local control and to improve
long-term survival.
PMID- 29963142
TI - Thin-wall cystic lung cancer: A study of 45 cases.
AB - Thin-wall cystic lung cancer is uncommon. Consequently, there is a lack of
knowledge concerning the features of this type of lung cancer, which may lead to
misdiagnosis and delayed treatment. The aim of the present study is to understand
the invasiveness and metastasis of thin-wall cystic lung cancer. The prognosis of
this type of cancer will also be discussed. The present study attempted to
determine the pathological interpretation of the imaging results. A total of 45
patients with this specific type of lung cancer were analyzed retrospectively
based on the review of medical records, radiological findings, pathological
changes and treatment strategies. Certain patients were also telephoned in order
to learn about their recent physical conditions. Thin-wall cystic lung cancer
displayed suspected malignant signs. The majority of these cases are
adenocarcinoma, but certain cases of squamous cell carcinoma may also display
cysts on their images. Although thin-wall cystic lung cancer is often thought to
progress slowly, certain cases may progress rapidly. Distant metastasis, which is
relatively rare, occurred in three cases. Cancer cells proliferate along the
terminal bronchioles and destroy the lung tissues exposing the bronchial arteries
and adjacent bronchi. Therefore, separation in cysts on the images was observed.
In the majority of cases, the thin-wall cystic lung cancer proliferates slowly,
but in a few cases it may be very aggressive.
PMID- 29963143
TI - Global lipidomics reveals two plasma lipids as novel biomarkers for the detection
of squamous cell lung cancer: A pilot study.
AB - Lipids are known to serve important roles in energy storage, membrane structure
and signal transduction as well as in human cancers. In the present study,
lipidomics was employed in order to identify plasma lipid markers for the early
detection of lung cancer. Mass spectrometry was performed to profile 390
individual lipids in 44 plasma samples obtained from a training discovery cohort,
which included 22 patients with squamous cell lung carcinoma (SqCC) and 22 high
risk individuals. An additional cohort that included 22 high-risk individuals and
22 patients with SqCC was further used for validation. During the training stage,
a total of 20 distinct lipids that were significantly distributed between the
high-risk and SqCC cases, were identified. A panel of 2 lipid markers (C18:2
cholesterol esters and sphingomyelin 22:0) were then further defined using the
training accuracy values of 95.5% sensitivity, 90.9% specificity and 95.2% area
under the receiver operating characteristic curve (AUC). The validation accuracy
values applied for the additional cohort were 93.9% sensitivity, 92.9%
specificity and 98.7% AUC. Thus, in the present study, 2 lipid markers that were
able to discern SqCC patients from high-risk individuals with a high sensitivity,
specificity and accuracy, were identified. These results may provide vital
information for the development of a quick and safe blood test for the early
diagnosis of SqCC.
PMID- 29963144
TI - IL-33 notably inhibits the growth of colon cancer cells.
AB - Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a
cytokine within the IL-1 interleukin family that binds to the plasma membrane
receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been
extensively studied in its role in autoimmune diseases, host responses to
pathogens and allergens, and has been associated with tumorigenic effects in
cancer research. The present study was performed to investigate the effects of IL
33 on colon cancer cells, based off the previous data that have demonstrated an
anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on
proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells
were examined using clonogenic survival assays, proliferation and caspase-3
activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
labeling staining and immunocytochemistry. It was determined that the HCT-116
cells demonstrated an notable decrease in optical density value upon incubation
with IL-33, along with a decrease in the number of colonies, compared with the
controls. It was further determined that the anti-proliferative effect of IL-33
on HCT-116 cells was associated with downregulation of the pro-proliferative
molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing
effect of IL-33 on HCT-116 cells was associated with downregulation of the anti
apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken
together, the results indicated that IL-33 inhibits the growth of colon cancer by
suppressing cellular proliferation, whilst simultaneously promoting apoptosis.
PMID- 29963145
TI - Muscarinic cholinergic signaling and overactive bladder-like symptoms associated
with invasive bladder cancer.
AB - The objective of the present study was to explore the association between
muscarinic cholinergic signaling and urothelial bladder tumors. Possible
associations among overactive bladder (OAB) symptoms and bladder tumors were
retrospectively investigated using a multicenter Chinese database with
prospectively collected data since 2010. Firstly, it was demonstrated that OAB
symptoms, such as urgency, were more severe in patients with invasive bladder
cancer and were associated with a reduced prognosis. Following this, muscarinic
cholinergic receptor 3 (M3R) expression in urothelium was determined to be lower
in invasive cancer tissue than in adjacent non-cancerous tissue, yet M3R
upregulation was associated with a reduced progression free survival (PFS) time.
Additionally, it was also demonstrated that muscarinic cholinergic receptor 2
(M2R) was upregulated in the sub-urothelium, and this was also associated with a
reduced PFS time. Furthermore, it was determined that cholinesterase and
acetylcholinesterase were lower in invasive cancer than in non-invasive cancer.
In conclusion, the results indicated that M3R expression was downregulated in
invasive bladder cancer, which may have a role as a protective anti-oncogene, in
contrast to its oncogenic role in numerous other cancer types. Therefore,
muscarinic cholinergic signaling may be a novel therapeutic target for treating
bladder cancer.
PMID- 29963146
TI - Overexpressing modified human TRbeta1 suppresses the proliferation of breast
cancer MDA-MB-468 cells.
AB - A number of studies have indicated that thyroid hormone receptor beta1 (TRbeta1)
functions as a tumor suppressor. TRs mediate transcriptional responses through a
highly conserved DNA-binding domain (DBD). A novel rat TRbeta isoform
(rTRbetaDelta) was previously identified, in which a novel exon, N (108 bp), is
located between exons 3 and 4 within the DBD; this exon represents the only
difference between rTRbetaDelta and rTRbeta1. In vitro, rTRbetaDelta exhibits a
stronger tumor-suppressive capacity than rTRbeta1, and further analysis revealed
a high level of conservation between the rat and human DBD sequences. In the
present study, an artificially modified human TRbeta1 (m-hTRbeta1) was
constructed via the introduction of the 108-bp sequence into the corresponding
position of the wild-type human TRbeta1 (wt-hTRbeta1) DBD. An electrophoretic
mobility shift assay and transfection experiments confirmed that m-hTRbeta1 is
functional. Overexpression of m-hTRbeta1 inhibits the proliferation of MDA-MB-468
cells in the presence of triiodothyronine by promoting apoptosis, which may be
associated with the upregulation of Caspase-3 and Bak gene expression and the
activation of the Caspase-3 protein. In addition, the pro-apoptotic effect of m
hTRbeta1 was stronger, compared with wt-hTRbeta1. These results indicated that m
hTRbeta1 may act as a tumor suppressor in MDA-MB-468 cells. These data provided a
novel insight into gene therapy for breast cancer.
PMID- 29963147
TI - MicroRNA-139-5P inhibits human prostate cancer cell proliferation by targeting
Notch1.
AB - Despite an improvement in the efficacy of chemotherapeutic agents, the outcome of
patients with prostate cancer remains poor. MicroRNA (miRNA/miR)-139 expression
is often downregulated in multiple types of tumor, including in prostate cancer.
The aim of the present study was to investigate the inhibitory effect of miR-139
on the PC-3, C4-2B and LNCaP prostate cancer cell lines. Analysis of the cell
cycle of PC-3, C4-2B and LNCaP cells transfected with miR-139 revealed a
significantly increased percentage of cells in the G1 phase and a decreased
percentage in the S and G2 phases compared with those transfected with a negative
control miRNA. The growth inhibitory rate of miR-139-transfected cells 24, 48 and
72 h after transfection were 32.83+/-2.61, 52.58+/-3.2 and 62.36+/-4.55% in PC-3
cells; 30.28+/-2.25, 51.74+/-3.27 and 60.80+/-3.58% in C4-2B cells; and 33.20+/
2.67, 51.83+/-3.59 and 61.79+/-4.85% in LNCaP cells, respectively. The present
study revealed that miR-139 inhibited the proliferation of prostate cancer cells
by interfering with the cell cycle. Further study into the mechanism by which
this happened suggested that miR-139 reduced cyclin D1 expression and inhibited
cell proliferation through targeting Notch1.
PMID- 29963148
TI - FGFRL1 deficiency reduces motility and tumorigenic potential of cells derived
from oesophageal squamous cell carcinomas.
AB - Oesophageal squamous cell carcinoma (ESCC) is an aggressive cancer that resulted
in ~400,000 mortalities worldwide in 2012. It was reported previously that
fibroblast growth factor receptor-like 1 (FGFRL1) is highly expressed in ESCC
patients with lymph node metastasis and poor prognosis accordingly. FGFRL1 is an
FGFR that lacks tyrosine kinase activity, whereas the activity is critical for
other FGFRs to activate intracellular signalling. The mechanism by which FGFRL1
promotes the aggressiveness of ESCCs is unknown. In the present study, two
independent FGFRL1-deficient cell lines were generated from human ESCC KYSE520
cells, in order to investigate the relationship of FGFRL1 with the aggressiveness
of ESCCs. FGFRL1-deficiency did not affect proliferation of KYSE520 cells in
vitro. However, a xenograft mouse model demonstrated that FGFRL1-deficiency
decelerated tumour growth in vivo. The haematoxylin-eosin staining identified
that FGFRL1-deficient cells formed well-differentiated squamous cell carcinomas,
whereas wild-type cells formed moderately differentiated squamous cell
carcinomas. Microarray analysis of mRNA expression revealed that FGFRL1-depletion
resulted in decreased expression of proteins associated with motility and
invasion of tumour cells, matrix metalloproteinase-1 and fibroblast growth factor
binding protein 1. The wound-healing assay indicated that depleting FGFRL1
reduced cell motility. Furthermore, the invasiveness of FGFRL1-deficient cells
was lesser than that of wild-type KYSE520 cells. In the FGFRL1-deficient KYSE520
cells, actin filaments around the nucleus were observed sparsely, whereas the
filaments along the plasma membranes were observed as frequently as those in the
parent KYSE520 cells. These results demonstrate that FGFRL1 may be involved in
regulation of protein expression, actin filament assembly and tumorigenic
potential of ESCC cells.
PMID- 29963149
TI - Prognostic value of hsa-mir-299 and hsa-mir-7706 in hepatocellular carcinoma.
AB - This study aimed to investigate the expression of microRNA (miRNA) 299 and miRNA
7706 in patients with hepatocellular carcinoma (HCC), and to explore their
effects on proliferation of SK-HEP-1 HCC cells. Expression of miRNA-299 and miRNA
7706 in tumor tissue (HCC group) and adjacent healthy tissue (>30 mm away from
the tumor tissue) of 179 patients with HCC was determined by real-time polymerase
chain reaction (qRT-PCR). miR-299 mimics and miR-7706 mimics were transfected
into SK-HEP-1 HCC cells by RNA transfection. The proliferation and invasion of SK
HEP-1 cells were detected by CCK-8 kit and Transwell kit, respectively. Compared
with adjacent tissues, expression levels of miRNA-299 and miRNA-7706 in HCC group
were significantly downregulated. Analyses on the correlation between the
expression of miRNA-299 and miRNA-7706 and clinical factors showed that
expression levels of miRNA-299 and miRNA-7706 were significantly correlated with
pathological stages and lymph node metastasis. ROC curve analysis showed that the
areas under the curve were 0.837 and 0.845 for miRNA-299 and miRNA-7706 in the
prediction of HCC, respectively. Survival analysis showed that the 5-year overall
survival rate of patients with high expression levels of miRNA-299 and miRNA-7706
was significantly different from that of patients with low expression levels
(P=0.016). Compared with cells transfected with scramble mimics, proliferation
and invasion abilities of SK-HEP-1 cells transfected with miR-299 mimics and
miRNA-7706 were significantly weakened. Results suggested that downregulation of
miRNA-299 and miRNA-7706 can inhibit the proliferation of HCC cells and can be
used as a new target for the treatment of HCC.
PMID- 29963151
TI - miR-202-5p inhibits the migration and invasion of osteosarcoma cells by targeting
ROCK1.
AB - Many studies have shown that microRNA regulates the development and treatment of
osteosarcoma (OS). In many human cancer studies, the expression of microRNA-202
has been shown to be abnormal. The aim of the study was to examine the role of
miR-202-5p in the occurrence and formation of OS. miR-202-5p and Rho-associated
coiled-coil containing protein kinase 1 (ROCK1) levels were assessed using RT
qPCR in OS tissues and cell lines. The cell migrating and invasive abilities were
detected by the Transwell assay in OS. Moreover, the relationship between miR-202
5p and ROCK1 was verified via luciferase reporter assay. The protein level of
ROCK1 was identified by western blot analysis. Downregulation of miR-202-5p was
identified in OS tissues and cell lines. In addition, the miR-202-5p
overexpression had inhibitory action for cell migration and invasion in OS.
Moreover, miR-202-5p directly targeted ROCK1 and negatively regulated its
expression. Upregulation of ROCK1 had a carcinogenic effect in OS. Furthermore,
the upregulation of ROCK1 restored the suppressive effect of miR-202-5p. miR-202
5p, in turn, weakened the abilities of cell migration and invasion in OS by
inhibiting ROCK1 expression. As a result, miR-202-5p may be developed as a
potential pathway in the reatment of OS.
PMID- 29963150
TI - Photodynamic diagnosis of peritoneal metastasis in human pancreatic cancer using
5-aminolevulinic acid during staging laparoscopy.
AB - Peritoneal metastasis is an important prognostic factor for pancreatic cancer.
The present study evaluated the possibility of diagnosing peritoneal metastasis
by a photodynamic diagnosis using 5-aminolevulinic acid (5-ALA-PDD). In vitro,
protoporphyrin IX (PpIX) accumulation was examined in the AsPC-1-GFP cell line
following 5-ALA hydrochloride administration. In vivo, AsPC-1-GFP cells were
injected into the peritoneal cavities of mice. Three weeks later 5-ALA
hydrochloride was intraperitoneally administered to the mice. The peritoneal
nodules were observed under fluorescence excitation. A total of 34 patients were
enrolled in the present study who were clinically diagnosed with pancreatic
malignancy. 5-ALA hydrochloride was orally administered to the patients prior to
surgery. During the operation the abdominal cavity was observed under white light
and fluorescence. In vitro and in vivo, it was confirmed that PpIX-induced red
fluorescence. In 9 patients peritoneal nodules suspected to be peritoneal
metastasis were observed under white light. In 4 of the 9 patients nodules were
detected on the basis of the fluorescence images. Fluorescent nodules were
histopathologically diagnosed as metastatic. In the present study it was
confirmed that 5-ALA-PDD holds promise for the rapid diagnosis of peritoneal
metastasis in patients with pancreatic cancer.
PMID- 29963152
TI - Suppression of chloride voltage-gated channel 3 expression increases sensitivity
of human glioma U251 cells to cisplatin through lysosomal dysfunction.
AB - The mechanism of cisplatin resistance is complex. Previous studies have indicated
that chloride voltage-gated channel 3 (CLCN3) is associated with drug resistance;
however, the mechanisms are not fully understood. Therefore, the present study
explored the involvement of CLCN3 in cisplatin resistance in human glioma U251
cells. The effects of combined cisplatin treatment and CLCN3 suppression on
cultured U251 cells were investigated. The decreased viability of cisplatin
treated U251 cells indicated the cytotoxic effects of CLCN3 silencing. Expression
of the apoptosis-related gene TP53 and caspase 3 activation were enhanced in
cisplatin-treated U251 cells. Furthermore, the ratio of BCL2/BAX expression was
decreased. Notably, CLCN3 suppression promoted cisplatin-induced cell damage in
U251 cells. Thus, the combined use of cisplatin and CLCN3 antisense had additive
effects in U251 cells. In addition, the present results indicated that CLCN3
suppression decreased lysosome stabilization in U251 cells treated with
cisplatin. To conclude, the present results indicated that CLCN3 suppression can
sensitize glioma cells to cisplatin through lysosomal dysfunction.
PMID- 29963153
TI - Primary endobronchial liposarcoma successfully resected via bronchoscopy: A rare
case report with genetic analysis.
AB - Liposarcoma is the most common type of soft-tissue sarcoma, and predominantly
originates from the extremities and retroperitoneal cavity. However, primary
endobronchial liposarcoma is extremely rare. The present study reports on the
case of a 54-year-old man, a smoker, diagnosed with primary endobronchial
atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLS), which was
successfully resected via bronchoscopy. Chest computed tomography (CT) revealed a
neoplasm in the left main bronchus measuring 12.8*7.8 mm. Bronchoscopy
demonstrated multiple roundish, pedunculated, polypoid masses in the left main
bronchus. Bioptic specimens were obtained from the roundish masses, and
pathological examination revealed an adipose tissue-derived tumor. The masses
were completely resected during the second bronchoscopy under general anesthesia.
Histopathological examination of the radical resection specimen revealed that it
was an ALT-WDLS. The patient showed good quality of life at the 6-month
postoperative follow-up without evidence of recurrence. Immunohistochemistry was
completed with the human homologue of murine double-minute type 2 (MDM2) (+),
cyclin-dependent kinase 4 (CDK4) (+), p16 (+), S-100 (+), Ki-67 (+), cluster of
differentiation 34 (CD34) (+) and retinoblastoma protein (+), confirming ALT
WDLS. However, the fluorescence in situ hybridization assay revealed no
amplification of MDM2 and CDK4 in the ALT-WDLS. To the best of our knowledge, the
present case report is the first to describe the clinicopathologic features and
genetic analysis of endobronchial liposarcoma. Although rare, this case is a
reminder that clinicians should consider the possibility of this rare
endobronchial tumor in patients with nonspecific symptoms including chronic
cough, chest pain and recurrent pneumonia. As in this case, endoscopic treatment
provided an excellent clinical outcome in patients with primary endobronchial ALT
WDLS.
PMID- 29963154
TI - Effect of allogeneic blood transfusion on levels of IL-6 and sIL-R2 in peripheral
blood of children with acute lymphocytic leukemia.
AB - Effect of allogeneic blood transfusion on the expression of interleukin-6 (IL-6)
and soluble interleukin-2 receptor (sIL-2R) in peripheral blood of children with
acute lymphoblastic leukemia (ALL) was investigated. A total of 91 ALL children
admitted to Nanfang Hospital from June 2014 to January 2017 were selected as the
study group. Patients were randomly divided into allogeneic blood transfusion
group (n=38) and non-transfusion group (n=53). In addition, a total of 64 healthy
children were also selected from June 2014 to January 2017 as the control group.
Patients in allogeneic blood transfusion group were transfused with red blood
cell suspension and machine-collected platelets, while patients in non
transfusion group were not treated with blood transfusion. Peripheral venous
blood was collected before and at 4, 8 and 12 weeks after blood transfusion to
prepare serum. Serum IL-6 and sIL-2R levels were measured by enzyme-linked
immunosorbent assay (ELISA). Before transfusion, serum levels of IL-6 and sIL-2R
were significantly lower in the study group than those in control group (p<0.05),
and no significant differences in serum levels of IL-6 and sIL-2R were found
between the allogeneic blood transfusion and non-transfusion group. After
transfusion, serum levels of IL-6 and sIL-2R were stable for 12 weeks in the non
transfusion group, while IL-6 and sIL-2R levels were significantly increased in
the allogeneic blood transfusion group. The results showed that serum level of IL
6 and sIL-2R was increased in ALL patients with allogeneic blood transfusion,
which resulted in reduced antibody production and decreased cellular immunity.
The patients had low immunity, and attention should be paid on the pathogen
infection prevention.
PMID- 29963155
TI - miR-211 inhibits proliferation, invasion and migration of cervical cancer via
targeting SPARC.
AB - Cervical cancer remains one of the most frequent gynecological malignancies among
females around the world. Therefore, fully understanding the molecular mechanisms
underlying the progression of cervical cancer may be critical for the development
of effective therapeutic strategies against cervical cancer. The object was to
evaluate the potential effect of miR-211 and verify its influence on the function
of secreted protein acidic and rich in cysteine (SPARC) in cervical cancer. It
was demonstrated that miR-211 was downregulated in cervical cancer cell lines
(HeLa and C33A) and cervical cancer specimens, while SPARC expression level was
higher in tumor tissues. We also revealed miR-211 upregulated expression could
inhibit cells proliferation, migration and invasion in vivo. SPARC was confirmed
as a direct and functional target of miR-211 and the inverse relationship between
them was also observed. The results of the present study suggest that miR-211
reduced cancer growth, migration and invasion, and suppresses the SPARC
expression in cervical cancer. This newly identified miR-211 may provide further
insight into the progression and offers a promising target for cervical cancer
therapy.
PMID- 29963156
TI - Computed tomography and magnetic resonance imaging features of cervical chordoma.
AB - Computed tomography (CT) and magnetic resonance imaging (MRI) scans of 11
patients with histologically proven cervical chordoma were retrospectively
evaluated. Imaging features assessed included location, morphology, association
with adjacent structures, vertebral destruction, status of cortical bone,
periosteal reaction, attenuation and calcification by CT, and signal intensity
and enhancement pattern by MRI. Of 7 cases with CT, 6 exhibited lytic-sclerotic
bone destruction. A total of 5 cases exhibited pressure erosion of outer cortex,
3 of which had spiculated periosteal reaction. Calcification was observed in 3
cases. All cases were heterogeneous and hypodense. MRI T2-weighted images (n=10)
revealed heterogeneous hyperintense (n=5), intermediate (n=2) and intermediate
hyperintense signal intensity (n=3). Hypointense septa between lobules (n=5) and
stripes (n=3) were observed on T2-weighted images. Post-contrast magnetic
resonance images (n=6) demonstrated marked heterogeneous (n=3) and ring-like
(n=3) enhancement. CT scanning is valuable in revealing the lytic-sclerotic bone
destruction, pressure erosion of outer cortex and calcification. MRI is useful in
demonstrating the results of soft tissue mass. The two examinations are necessary
for differential diagnosis of patients with suspected cervical chordoma.
PMID- 29963157
TI - Prognostic value of D-lactate dehydrogenase in patients with clear cell renal
cell carcinoma.
AB - Lactate dehydrogenase (LDH) is an enzyme involved in anaerobic glycolysis and is
associated with the prognosis of patients with renal cell carcinoma (RCC). The
human genome has four LDH genes: LDHA, LDHB, LDHC and LDHD. In order to determine
which of these four LDH genes may predict clear cell RCC (ccRCC), a total of 509
patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort and 192 patients
with ccRCC from the Fudan University Shanghai Cancer Centre (FUSCC) cohort were
enrolled in the present study. The expression profiles of LDHD genes in the TCGA
cohort were obtained from the TCGA RNAseq database. The Cox proportional hazards
regression model and Kaplan-Meier curves were used to assess relative factors.
The LDH family genes that were revealed to have an association with overall
survival (OS) were further validated in the FUSCC cohort. In the TCGA cohort,
following Cox proportional hazards analysis, LDHD expression (P=0.0400; hazard
ratio, 0.872; 95% confidence interval, 0.764-0.994) was revealed to be predictive
of the prognosis of patients with ccRCC. Further analysis revealed that low LDHD
expression (P<0.0001) was significantly associated with a poor prognosis in terms
of OS. Additionally, the expression of LDHD (P<0.0001) was significantly
different in patients with ccRCC compared with paired controls. In the FUSCC
cohort, low LDHD expression was also associated with a poor OS (P=0.0103), and
the tumour pathological T stage was a factor that influenced the expression of
LDHD (P=0.0120). Furthermore, the expression of LDHD influenced the serum LDH
level (P=0.0126). The downregulation of LDHD expression may be a predictor of
poor prognosis in patients with ccRCC.
PMID- 29963158
TI - Disappearance of bone metastases in chemotherapy-resistant gastric cancer treated
with antigen peptide-pulsed dendritic cell-activated cytotoxic T lymphocyte
immunotherapy: A case report.
AB - The adoptive transfer of cytotoxic T lymphocytes (CTLs) stimulated by specific
tumor antigen peptide-pulsed dendritic cells (DCs) is one of the most promising
immunotherapeutic strategies currently available for patients with gastric cancer
(GC). The present case report describes a patient with chemotherapy-resistant
stage IV GC with multiple bone metastases, who had been treated with antigen
peptide-pulsed DC-CTLs. DCs and CTLs were transfused into the patient
subcutaneously and intravenously with simultaneous oral administration of low
dose cyclophosphamide. Following 3 cycles of combination therapy, marked
remission regarding the number of metastatic bone lesions was achieved, confirmed
by the use of enhanced computerized tomography, computerized tomography and
magnetic resonance imaging. After 1 year, 8 cycles of adoptive immunotherapy were
administered, and a further decrease in the number of metastatic bone lesions was
observed in addition to a marked improvement in the patient's quality of life.
Therefore, personalized antigen peptide-pulsed DC-CTLs combined with oral
administration of low-dose cyclophosphamide may serve as a promising anticancer
therapy to eradicate tumor cells, and therefore this approach is recommended for
future cases of a similar nature.
PMID- 29963159
TI - Comprehensive analysis of differentially expressed profiles of lncRNAs and mRNAs
reveals ceRNA networks in the transformation of diffuse large B-cell lymphoma.
AB - Diffuse large B-cell lymphoma (DLBCL) is one of the malignancies with a high
mortality rate. The molecular mechanisms involved in transformation of DLBCL
remain unclear. Therefore, it is critically important to investigate the
biological mechanisms of DLBCL. Accumulating evidence indicates that long non
coding RNAs (lncRNAs) serve key functions in tumorigenesis, cancer progression
and metastasis. Compared with follicular lymphoma (FL), a total of 123
upregulated lncRNAs and 192 downregulated lncRNAs in DLBCL were identified.
Subsequently, a specific DLBCL-associated competing endogenous RNA (ceRNA)
network and a specific FL-associated ceRNA network was constructed. Gene Oncology
and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that
differentially expressed lncRNAs served key functions in regulating signal
transduction, transcription, cell adhesion, development and protein amino acid
phosphorylation. Furthermore, the molecular functions of PRKCQ antisense RNA 1,
HLA complex P5, OIP5 antisense RNA 1, growth arrest specific 5 and taurine
upregulated 1 were investigated, and it was revealed that these lncRNAs served
important functions in regulating a series of biological processes, including
anti-apoptosis, cell cycle, DNA repair, response to oxidative stress and
transcription. The present study may provide a potential novel therapeutic and
prognostic target for the treatment of DLBCL.
PMID- 29963160
TI - Long non-coding RNA CACNA1G-AS1 promotes calcium channel protein expression and
positively affects human keloid fibroblast migration.
AB - Keloids are a type of benign hyperplasia that cause dermatologic dysfunction and
esthetic deformity by invading adjacent normal tissues. Little is known about
their etiology, therefore, they are a challenge to treat using plastic surgery.
In a previous study, it was demonstrated that the expression of the long non
coding RNA CACNA1G-AS1 (CAS1) is high in keloid tissue, suggesting that CAS1 is
involved in keloid formation. In the present study, the aim was to identify
potential keloid target proteins by exploring CAS1 biological function during
cell proliferation and migration, cytokine secretion, collagen secretion and the
control of calcium channel protein expression in human keloid fibroblasts. Three
biopsy samples were collected from each patient with keloids at The Peking Union
Medical College Hospital, which were then used to investigate the role of CAS1 in
cell proliferation and migration. CAS1 silencing was also carried out using small
interfering RNA; cell factors, collagen and calcium channel protein levels were
compared with control cells. The interference of CAS1 expression reached 50%
compared with the control group. CACNA1G and type I collagen expression was
significantly downregulated by CAS1 knockdown, while the expression of
transforming growth factor-beta and type III collagen was not affected. Wound
healing time was longer in the CAS1-knockdown group, but there was no visible
change in cell proliferation. In conclusion, CAS1 appeared to promote calcium
channel protein and type I collagen expression, and to have a positive effect on
cell migration in human keloid fibroblasts. Therefore it has potential as a novel
therapeutic target for keloids.
PMID- 29963161
TI - Ellagic acid and Sennoside B inhibit osteosarcoma cell migration, invasion and
growth by repressing the expression of c-Jun.
AB - Osteosarcoma is a mesenchymally derived, high-grade bone sarcoma that is the most
frequently diagnosed primary malignant bone tumor. Today, chemoprevention is
regarded as a promising and realistic approach in the prevention of human cancer.
Previous studies have suggested ellagic acid (EA) and Sennoside B have potential
in this regard. The aim of the present study was to elucidate the anti
osteosarcoma effects of EA and Sennoside B by using Saos-2 and MG63 osteosarcoma
cells. It was identified that EA or Sennoside B treatment could inhibit the
growth, migration and invasion of the cells, and induce G1 cell cycle arrest by
repressing the transcription of c-Jun. These results may provide a cellular basis
for the application of EA or Sennoside B in the treatment of patients with
osteosarcoma.
PMID- 29963162
TI - Vitamin D and DDX4 regulate the proliferation and invasion of ovarian cancer
cells.
AB - Ovarian cancer is one of the most commonly occurring types of cancer and one of
the most common causes of cancer-associated mortality in women. Diagnosis of
ovarian cancer at an early stage is difficult due to the lack of specific
symptoms. In the present study, it is demonstrated that active vitamin D
treatment prohibited the proliferation and invasion of ovarian cancer cells, and
the expression level of a germ cell specific marker DEAD (Asp-Glu-Ala-Asp)-box
helicase 4 (DDX4), which is overexpressed in ovarian cancer, was downregulated by
active vitamin D treatment. Knockdown of DDX4 by siRNA could also suppress the
invasive ability of ovarian cancer cells. Therefore, DDX4 may be considered as a
diagnostic marker of ovarian cancer, and vitamin D may be a candidate drug for
ovarian cancer therapy.
PMID- 29963163
TI - Comparative study on the diagnostic values of different ultrasound technologies
for malignant thyroid nodules.
AB - The present study compared and analyzed the diagnostic values of B-mode
ultrasound and elasticity imaging technology for the identification of benign and
malignant thyroid nodules. Ninety-four patients who were diagnosed with thyroid
nodules by ultrasound were chosen. All patients were checked with B-mode
ultrasound and ultrasound elasticity imaging technology before surgeries.
Further, the post-operative outcomes were compared with operation pathology. The
pathological examination results were taken as the gold standard. The accuracy,
sensitivity, specificity, positive predictive value and negative predictive
values of combined ultrasound diagnosis were all obviously higher than those by
the B-mode ultrasound and the ultrasound elastography method (P<0.05). In
conclusion, as a new technology, ultrasound elasticity imaging technology has
relatively high diagnositic value in identifying benign and malignant thyroid
nodules. With its own advantages and limitations, the ultrasound elasticity
imaging technology could effectively complement B-mode ultrasound, and improve
the sensitivity, specificity and accuracy of ultrasound diagnosis for thyroid
nodules.
PMID- 29963164
TI - Value of automatic DNA image cytometry for diagnosing lung cancer.
AB - The present study aimed to investigate the diagnostic value of automatic DNA
image cytometry (DNA-ICM) for diagnosing lung cancer. A total of three different
types of samples from 465 cases were included: Bronchoalveolar lavage fluid
(BALF), 386 samples; pleural effusion cases, 70 samples; and fine-needle
aspiration procedures, 9 samples. Two methods, liquid-based cytology (LBC) and
automatic DNA-ICM, were used to assess the samples, and the pathological results
of 120/465 cases were reviewed. The results of DNA-ICM were compared with those
of LBC and pathology. There were 57 cases of lung cancer without aneuploidy and
49 cases without evidence of malignant tumor, but with the presence of
heteroploid cells. The positive diagnostic rate for BALF samples using LBC was
significantly higher compared with that for DNA-ICM (P<0.05). No statistically
significant difference was observed in the positive diagnostic rate between DNA
ICM and LBC in pleural effusion samples. For DNA-ICM in BALF, pleural effusion
and all samples, no statistically significant differences were identified between
the positive diagnostic rates of lung squamous carcinoma and lung adenocarcinoma.
The positive diagnostic rate of LBC combined with DNA-ICM was not significantly
improved. In non-small cell lung cancer (NSCLC) cases, the difference in the
maximum value of DNA (DNAmax) was positively correlated with tumor stage
(P<0.05), but no significant correlations were observed among DNA max, tumor type
and tumor location. In small-cell lung cancer (SCLC) cases, no significant
correlations were observed among DNAmax, tumor staging or tumor location. The
differences in the DNAmax values of squamous cell carcinoma, adenocarcinoma, SCLC
and NSCLC were not statistically significant. In the present study, the area
under the receiver operating characteristic curve for LBC (0.936) was
significantly greater compared with that for DNA-ICM (0.766) (P<0.05). DNA-ICM
has medium diagnostic value in lung cancer, and the DNAmax was positively
correlated with tumor stage in NSCLC. DNA-ICM may serve as a supplement to LBC,
but it is not recommended as a sole procedure for lung cancer screening.
PMID- 29963165
TI - Knockdown of FUT3 disrupts the proliferation, migration, tumorigenesis and TGF
beta induced EMT in pancreatic cancer cells.
AB - Fucosyltransferases (FUTs) are critical for glycoproteins and glycolipid chains
and serve an important role in the adhesive interaction between selectins and
their ligands, which contribute to tumor cell spread and metastasis. While
multiple cancer cell lines heavily express FUT3, the present study investigated
the expression level of FUT3 in different human pancreatic cancer cell lines.
Forced expression and knockdown of FUT3 in different pancreatic cancer cell line
demonstrated that FUT3 is important in cell proliferation. Using wound healing
and transwell assays, it was observed that the migratory ability was decreased in
FUT3 downregulated Capan-1 cell line, compared with the normal Capan-1 cell line.
Furthermore, it was demonstrated that the knockdown of FUT3 impaired the adhesion
of Capan-1 with E-selectin and inhibited transforming growth factor (TGF)-beta
induced epithelial-mesenchymal transition. These data suggest that the knockdown
of FUT3 inhibits the tumorigenesis in vivo and FUT3 may be a promising target
aiming at reducing the metastatic virulence of pancreatic cancer cells.
PMID- 29963166
TI - Pro-apoptotic effects of Kangfuxin on human stomach cancer cells and its
underlying mechanism.
AB - Kangfuxin (KFX) is an oral liquid derived from Periplaneta americana, with
complex components. KFX has been demonstrated to exhibit anticancer activity in a
variety of different types of tumor, including gastric cancer; however, its
underlying molecular mechanism remains unclear. The present study was designed to
investigate the pro-apoptotic effects of KFX on SGC-7901 cells, in order to
provide a theoretical basis for clinical application. In order to clarify the pro
apoptotic effects of KFX on SGC-7901 cells, MTT analysis was conducted. To
evaluate the anticancer effect of KFX, peroxisome proliferator-activated receptor
(PPAR)-gamma was analyzed by reverse transcription-polymerase chain reaction.
Western blot analysis was used to determine the effects of KFX on the expression
of cleaved caspase-3, phosphorylated extracellular signal-regulated kinase (p
ERK), ERK, tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated
X, interleukin (IL)-6 and IL-1beta. In addition, terminal deoxynucleotidyl
transferase-mediated dUTP nick-end labeling (TUNEL) analysis was used to detect
apoptosis in SGC-7901 cells. It was revealed that PPAR-gamma was increased in SGC
7901 cells following treatment with KFX, shown by an increase in mRNA expression.
Furthermore, western blot analysis identified that KFX treatment groups exhibited
markedly inhibited levels of Bcl-2, IL-6, IL-1beta and p-ERK, and induced p53
protein expression. Additionally, TUNEL and MTT assays demonstrated that
treatment with KFX may induce SGC-7901 cell apoptosis and inhibit proliferation.
In conclusion, to the best of our knowledge, the results of the present study
demonstrated for the first time that KFX may induce SGC-7901 cell apoptosis and
inhibit its proliferation, and this may be primarily attributed to its role in
mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase/ERK
signaling pathway inhibition.
PMID- 29963167
TI - Cyclooxygenase-2 induces angiogenesis in pancreatic cancer mediated by
prostaglandin E2.
AB - The purpose of the present study was to elucidate the effects of cyclooxygenase 2
(COX-2) on the expression of vascular endothelial growth factor (VEGF) and
prostaglandin E2 (PGE2) in pancreatic cancer in vitro and in vivo, and to clarify
the potential mechanism of COX-2-induced angiogenesis of pancreatic cancer. The
study analysis was conducted in the pancreatic cancer PC-3 cell line. The
expression of COX-2 and VEGF in human pancreatic cancer tissue was analyzed by
immunohistochemistry. Angiogenesis was detected using immunohistochemistry with
anti-collagen IV antibodies, and was calculated according to the microvascular
density (MVD). In vitro analysis was performed using ELISA or radioimmunoassay
(RIA). The effect of exogenous PGE2 on the downregulation of VEGF by Celebrex was
also assessed. In vivo analysis was performed using western blotting or RIA.
Concurrently, MVD was also investigated in nude mice using immunohistochemistry
with anti-collagen IV antibodies. COX-2 was overexpressed in pancreatic cancer
tissues, with an overall positive rate of 87.5%. There was a positive association
between the expression of COX-2 and MVD. The in vitro study indicated that
Celebrex suppressed the expression of VEGF and PGE2 in PC-3 cells in a dose- and
time-dependent manner, while exogenous PGE2 rescued the expression of VEGF, which
was suppressed by Celebrex, in a dose-dependent manner. The in vivo study
revealed that the administration of Celebrex to xenograft nude mice significantly
inhibited the expression of VEGF and PGE2. These data provide evidence that PGE2
may be an important mediator between COX-2 and VEGF expression in the process of
angiogenesis in pancreatic cancer.
PMID- 29963168
TI - DEP domain containing 1 suppresses apoptosis via inhibition of A20 expression,
which activates the nuclear factor kappaB signaling pathway in HepG2 cells.
AB - A previous study revealed that DEP domain containing 1 (DEPDC1) is involved in
the carcinogenesis of bladder cancer via forming a complex with zinc finger
protein 224 (ZNF224) to suppress A20 expression, resulting in the activation of
the nuclear factor (NF)-kappaB signaling pathway; however, the role of DEPDC1 in
liver cancer remains unclear. Hep G2 cells were treated with 11R-DEP: 611-628, a
peptide capable of disrupting the DEPDC1-ZNF224 complex. Cell proliferation was
examined using an MTT assay and apoptosis was analyzed via detection of the
apoptotic marker caspase-3 using western blot analysis. A20 expression was
examined via reverse transcription-quantitative polymerase chain reaction and NF
kappaB subcellular localization was determined via immunofluorescence staining.
microRNA (miR)-130a was overexpressed in HepG2 cells and its effects on
proliferation and apoptosis were examined. The results demonstrated that 11R-DEP:
611-628 (3 uM) and miR-130a inhibited cell proliferation and promoted apoptosis
in HepG2 cells by activating A20 expression, which blocks the nuclear
transportation of NF-kappaB. In addition, the results demonstrated that the 11R
DEP: 611-628 (3 uM) treatment resulted in downregulation of DEPDC1 expression,
indicating that DEPDC1 expression is regulated by the DEPDC1-ZNF224 complex. In
conclusion, the data indicated that DEPDC1 suppresses apoptosis to promote cell
proliferation through the NF-kappaB signaling pathway in HepG2 cells and that
DEPDC1 is a potential target for the treatment of liver cancer.
PMID- 29963169
TI - Effect of postoperative systemic antipsychotic therapy on psychiatric recurrence
in patients with meningiomas.
AB - A number of patients with meningiomas and psychiatric disorders will suffer
psychiatric symptom recurrence following tumorectomies. The present study
reported a retrospective analysis regarding 42 cases of patients with meningiomas
using complete clinical follow-up data from June 2005 to June 2013. The patients
were divided into the systemic antipsychotic (SP) group (n=20) following 6months
of postoperative SP therapy and the none-SP (NSP) group (n=22), who did not
receive postoperative antipsychotic treatment. Patients were assessed using the
Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale
(BPRS) at the time points of prior to surgery, immediately following surgery, and
6 months, 12 months and 3 years following surgery. The effective rate, recurrence
rate, rehospitalization rate and survival analysis were calculated. The BPRS
score and PANSS scores (including PANSS positive, PANSS negative, PANSS general
psychopathology and PANSS overall) in the SP group at 6 months, 12 months and 3
years following surgery were significantly decreased compared with the NSP group
(P<0.05). The effective rate was 95, 90 and 90% at 6 months, 12 months and 3
years, respectively, in the SP group, whilst it was 68.2, 63.6 and 59%,
respectively, in the NSP group, which was statistically significant (chi2=4.89,
chi2=4.01 and chi2=5.12; P<0.05). The recurrence rate of the SP group was 0, 5
and 10% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group
it was 22.7, 31.8 and 54.5%, respectively, which was statistically significant
(chi2=5.16, chi2=4.89 and chi2=9.34; P<0.05). The rehospitalization rate of the
SP group was 0, 0 and 5% at 6 months, 12 months and 3 years, respectively, whilst
in the NSP group it was 13.6, 22.7 and 36.4%, respectively, and the data at 12
months and 3 years was statistically significant (chi2=5.16 and chi2=6.12;
P<0.05). Kaplan-Meier survival analysis indicated that the accumulative survival
rates of recurrence and rehospitalization in the SP group were improved compared
with the NSP group. The log-rank of recurrence was chi2=9.369 (P=0.002) and the
log-rank of rehospitalization was chi2=6.330 (P=0.012). In conclusion,
postoperative SP therapy is of great importance to the consolidation of mental
symptoms in patients with meningiomas and psychiatric symptoms, and it may
significantly reduce the recurrence and rehospitalization rates.
PMID- 29963170
TI - IMRT dose verification considering passing rate and respiratory motion.
AB - The aim of the present study was to investigate the association between the
dynamic intensity-modulated radiation therapy planned gamma analysis passing rate
and respiratory amplitude (A) and period (T) for different tumor volumes. A total
of 30 patients with malignant lung tumors were divided into three groups: A; B;
and C. The average tumor volumes (V) in the A, B and C groups were 635, 402 and
213 cm3, respectively. The simulated A values were set at 0, 5, 10, 15, 20 and 25
mm. The T values were set at 4, 5 and 6 sec. The gamma analysis passing rate was
calculated under different conditions (dose difference, 3%; distance difference,
3 mm). Compared with the gamma analysis passing rate in the A group (A=0, static;
T=4, 5, 6 sec), the gamma analysis passing rate deviation (A=5 mm) was <3.3%.
However, this difference was not statistically significant (P>0.05). With a
gradual increase in A value, the passing rate decreased. The deviation between
the 3 groups was <2.5% at the same A value (T=4, 5 and 6 sec). A descending trend
of passing rate with increased A value was revealed. At the same A and T values,
the passing rate decreased with decreased tumor volume. At the same tumor volume,
the passing rate decreased when the A value increased. The respiratory cycle was
not demonstrated to be associated with the passing rate. Overall, these results
suggest that the A value should be controlled in clinical radiotherapy.
PMID- 29963171
TI - Elevated GPC3 level promotes cell proliferation in liver cancer.
AB - The aim of the present study was to investigate the biological role of glypican 3
(GPC3), and to identify its mechanism and clinical significance in the
carcinogenesis of liver cancer. A total of 114 patients with liver cancer were
involved. Their clinical data, hematoxylin and eosin-stained and Antigen Ki-67
protein (Ki-67) and GPC3 immunohistochemically-stained liver cancer tissue
sections were analyzed to evaluate the correlation between the liver cancer
proliferation, differentiation and GPC3 expression. Fluorescence microscopy,
western blotting, MTT and reverse transcription quantitative polymerase chain
reaction (RT-qPCR) assays were performed in HepG2 and HLE cell lines to
investigate the potential mechanisms of action. Among the 114 patients with liver
cancer enrolled in the present study, 12 exhibited well-differentiated liver
cancer, of which 6 (50%) were positive for GPC3. A total of 30 cases exhibited
poorly differentiated liver cancer; 26 (87%) of these expressed GPC3 and 11 cases
(37%) demonstrated strong positive expression levels. The other 72 liver cancer
cases were moderately differentiated; 75% (54/72) of these expressed GPC3 and
12.5% (9/72) exhibited strong positive expression levels. There was a significant
association between the levels of GPC3 expression and liver cancer
differentiation (chi2=16.306, P=0.008). Ki-67 staining as the criteria of the
liver cancer cell proliferation index also indicated a cross correlation between
liver cancer proliferation and GPC3 levels. Among the 39 liver cancer samples
with a cell proliferation index <5%, only 2.6% (1/39) exhibited strong positive
GPC3 staining, but of the 16 cases with a high cell proliferation index >50%, 6
exhibited strong GPC3 staining (37.5%). The difference of cell proliferation
indexes between cancer cells were well, moderate and poorly differentiated, and
was markedly significant (chi2=26.334, P=0.002), and suggested that liver cancer
cell proliferation was positively correlated with GPC3 expression (r=0.316,
P=0.001). Consistently, in vitro analysis indicated that GPC3 promoted HepG2 and
HLE cell growth, which was more apparent in HepG2 cells. The RT-qPCR results
indicated that GPC3 promoted proliferation through the Hedgehog (Hh) pathway in
HepG2 cells, but not in HLE cells. In the present study, it was demonstrated that
patients with liver cancer with higher GPC3 levels exhibited poorer
differentiation and higher proliferation levels. In vitro GPC3 may promote liver
cancer cell lines proliferation through the Hh pathway.
PMID- 29963172
TI - Establishment and characterization of a GES-1 human gastric epithelial cell line
stably expressing miR-23a.
AB - MicroRNAs (miRNAs/miRs) are highly conserved, endogenous, small and single
stranded RNA molecules that promote the degradation and translational inhibition
of specific target mRNAs in order to regulate cell proliferation and
differentiation, and organism growth and development. MiR-23a has been
demonstrated to function as an oncogene in certain types of tumor. The aim of the
present study was to provide a tool for elucidating the mechanisms of action of
miR-23a in gastric cancer, and identify the function of miR-23a in a human
gastric epithelium cell line, by establishing a human gastric epithelial GES-1
cell line that stably expressed miR-23a. A plasmid was constructed for the
expression of miR-23a by inserting the miR-23a primary sequence into a pcDNA3
vector (pcDNA3/pri-23a). PcDNA3/pri-23a or the empty pcDNA3 vector (EV), which
was then transfected into human gastric epithelium GES-1 cells using
Lipofectamine to produce GES-1/miR-23a cells and GES-1/EV cells, respectively.
G418 (Geneticin) was used to select and expand the G418-resistant colonies, and
miR-23a expression was assessed by reverse transcription-semi-quantitative
polymerase chain reaction. The proliferation of the cells was assessed using cell
counting and MTT assays. The invasive ability of the cells was evaluated using a
Transwell assay. The colony-forming ability of the cells was assessed using a
colony formation assay. A human gastric epithelium GES-1/miR-23a cell line with
the stable expression of miR-23a was successfully established. Compared with the
control GES-1 and GES-1/EV cells, the mRNA expression of the miR-23a gene in GES
1/miR-23a cells was significantly increased (P<0.05). The proliferation rate,
invasive ability and colony-forming ability of the GES-1/miR-23a cells were
significantly higher compared with those of the control GES-1/EV cells and the
parental GES-1 cells (P<0.05). Additionally, the results of the present study
demonstrated that miR-23a enhanced the cell proliferation rate, invasive ability
and cell colony forming ability of GES-1 cells. This data provides a solid
experimental foundation for further studies on the function of miRNAs in the
development and progression of gastric cancer.
PMID- 29963173
TI - miR-222 promotes invasion and migration of ovarian carcinoma by targeting PTEN.
AB - Ovarian carcinoma is the most lethal of the gynecologic malignancies worldwide.
Increasing evidence suggests dysfunction of microRNAs (miRNAs) plays an important
role in human cancers. The function of miR-222 was detected in ovarian carcinoma
to verify the regulation of phosphatase and tensin homolog (PTEN) by miR-222. miR
222 expression in ovarian carcinoma tissues and cell lines were examined using RT
qPCR. Transwell assay was used to detect miR-222 effects on ovarian carcinoma
cell migration and invasion. Western blot analysis and luciferase assays were
performed to validate PTEN as miR-222 targets. miR-222 expression was upregulated
in ovarian carcinoma tissues and three cell lines (A2780, SKOV-3 and OVCAR-3).
Ectopic overexpression of miR-222 in ovarian carcinoma cells was sufficient to
promote invasion and migration. PTEN acted as a direct target of miR-222.
Overexpression of PTEN inhibited human ovarian carcinoma cell migration and
invasion. In summary, our findings suggest that miR-222 plays an important role
in promoting ovarian carcinoma cell invasion and migration and miR-222/PTEN may
be a novel therapeutic target of miRNA-mediated promotion of cell invasion and
migration in ovarian carcinoma.
PMID- 29963174
TI - Effect on the liver cancer cell invasion ability by studying the associations
between autophagy and TRAP1 expression.
AB - Liver cancer is one of the leading causes of cancer associated mortality,
particularly in eastern Asia. Autophagy serves an important role in
carcinogenesis. Previous studies have reported that TRAP1 is a novel and
efficient therapeutic target in various tumors. However, the associations between
autophagy and TRAP1 is not clear. In the present study, autophagy activity and
TRAP1 expression were examined in 4 different liver cancer cell lines (HepG2,
Hep3B2.1-7, Sk-hep1 and HepG2.2.15) with or without rapamycin induction. The cell
autophagy level was validated by monodansylcadaverine fluorescent staining, and
the expression levels of Beclin1 and light chain (LC)-3-II/LC3-I. The mRNA and
protein expression levels of tumor necrosis factor receptor-associated protein-1
(TRAP-1), Beclin1 and LC3-II/LC3-I were measured by reverse transcription
quantitative polymerase chain reaction, Protein Simple Western and western blot
analysis. HepG2 cells, with medium invasive ability, exerted the highest basal
level of autophagy and TRAP1 expression. In addition, hepatitis B (HBV) infection
in HepG2 cells inhibited autophagy activity and TRAP1 expression. Rapamycin
treatment also significantly enhanced autophagy in the 4 liver cancer cell lines
and increased TRAP1 expression in HepG2, Hep3B2.1-7 and Sk-hep1 cells. Thus, the
cell invasive ability, HBV infection and autophagy induction had different
effects on TRAP1 expression, and TRAP1 may be associated with autophagy in liver
cancer.
PMID- 29963175
TI - Analysis of miR-148b expression differences in stage-I and II parosteal
osteosarcoma.
AB - Expression of human serum albumin-micro RNA miR-148b in patients with stage-I and
II parosteal osteosarcoma and its effect on prognosis were investigated. A total
of 47 cases of fresh tissues of stage-I and II parosteal osteosarcoma and the
corresponding para-carcinoma normal bone tissues resected by operation were
collected; the expression of miR-148b in parosteal osteosarcoma tissues and
normal bone tissues was detected, and the correlations of miR-148b expression in
parosteal osteosarcoma tissues with clinicopathological parameters and prognosis
were analyzed. The expression level of miR-148b in parosteal osteosarcoma tissues
was significantly lower than that in para-carcinoma normal tissues (P<0.05). It
was found that the low expression of miR-148b was correlated with the lung
metastasis (P<0.05). Moreover, Kaplan-Meier survival curve analysis showed that
the overall survival rate of patients in the low-expression miR-148b group was
lower than that in the high-expression group (P<0.05). Multivariate Cox
regression analysis revealed that the miR-148b level (P=0.003) was an independent
prognostic factor affecting the prognosis. The results of this study showed that
the expression of miR-148b in stage-I and II parosteal osteosarcoma tissues
declines, which is related to the poor clinical prognosis of parosteal
osteosarcoma.
PMID- 29963176
TI - Identification of key pathways and genes in the progression of cervical cancer
using bioinformatics analysis.
AB - The aim of the present study was to investigate the key pathways and genes in the
progression of cervical cancer. The gene expression profiles GSE7803 and GSE63514
were obtained from the Gene Expression Omnibus database. Differentially expressed
genes (DEGs) were identified using GEO2R and the limma package, and Gene Ontology
(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were
conducted using the Database for Annotation, Visualization and Integrated
Discovery. The hub genes were identified using Cytoscape and protein-protein
interaction (PPI) networks were constructed using the STRING database. A total of
127 and 99 DEGs were identified in the pre-invasive and invasive stages of
cervical cancer, respectively. GO enrichment analysis indicated that the DEGs in
pre-invasive cervical cancer were primarily associated with the 'protein
binding', 'single-stranded DNA-dependent ATPase activity', 'DNA replication
origin binding' and 'microtubule binding' terms, whereas the DEGs in invasive
cervical cancer were associated with the 'extracellular matrix (ECM) structural
constituent', 'heparin binding' and 'integrin binding'. KEGG enrichment analysis
revealed that the pre-invasive DEGs were significantly enriched in the 'cell
cycle', 'DNA replication' and 'p53 signaling pathway' terms, while the invasive
DEGs were enriched in the 'amoebiasis', 'focal adhesion', 'ECM-receptor
interaction' and 'platelet activation' terms. The PPI network identified 4 key
genes (PCNA, CDK2, VEGFA and PIK3CA), which were hub genes for pre-invasive and
invasive cervical cancer. In conclusion, bioinformatics analysis identified 4 key
genes in cervical cancer progression (PCNA, CDK2, VEGFA and PIK3CA), which may be
potential biomarkers for differentiating normal cervical epithelial tissue from
cervical cancer.
PMID- 29963177
TI - Clinical features and survival analysis of clear cell papillary renal cell
carcinoma: A 10-year retrospective study from two institutions.
AB - Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized
subtype of renal cell carcinoma entity, however, little is known about its
clinical features. In the present study, 26 cases of CCPRCC were screened out
from two institutions. The patient data, tissue pathology, immunohistochemical
phenotype, computed tomographic images and survival analysis were studied. The
mean age was 53.3 years and the average tumor size was 2.5 cm. A total of 17
patients' body mass indexes were higher than the normal level. A total of 11
patients had hypertension and 6 patients had a smoking history.
Histopathologically, all cases of CCPRCC exhibited a tubular and papillary
architecture, small to medium-sized cuboidal tumor cells with clear cytoplasms,
and a low Fuhrman nuclear grade. All tumors were encapsulated by variably thick
fibrous capsules. Immunohistochemistry showed diffuse and moderate to strong
cytoplasmic staining for CK7, CA IX and vimentin, but negative for AMACR and CD10
(sometimes focally positive) in all cases. According to the results of Ki67
labeling index, the expression of Ki67 in CCPRCC was much lower than that in
clear cell renal cell carcinoma (CCRCC) (2.19 vs. 7.07%, P<0.001) and that in
papillary renal cell carcinoma (PRCC) (2.19 vs. 6.65%, P<0.001).
Radiographically, the tumors were shown as small masses with smooth contour and
mixed enhancement pattern. The multiphasic attenuation curve for CCPRCC, like
that for CCRCC, increased in the corticomedullary phase markedly and decreased in
the nephrographic phase and excretory phase gradually. At a median follow-up
period of 50 months, no cancer-specific death or tumor recurrence was observed.
Considering the favorable prognosis of CCPRCC, preoperative biopsy in order to
make clear the diagnosis is particularly important. In light of the present
findings, partial nephrectomy for patients with CCPRCC is recommended. If the
patients cannot tolerate surgery, closed monitoring or radiofrequency ablation
may be considered.
PMID- 29963178
TI - S-trityl-L-cysteine, a novel Eg5 inhibitor, is a potent chemotherapeutic strategy
in neuroblastoma.
AB - Eg5 is a member of the kinesin-5 family. It is involved in the formation of the
bipolar spindle and serves a crucial role in mitosis; meaning that mitotic
activation may serve as a chemotherapeutic strategy. However, the anticancer
activity of Eg5 inhibitors in neuroblastoma remains uncharacterized. In the
present study, the expression of Eg5 was examined in clinical tissue samples and
neuroblastoma cell lines, SK-N-SH, SH-SY5Y and SK-N-BE2. Additionally, the
antitumor activity of the Eg5 inhibitor, S-trityl-L-cysteine (STLC), was
confirmed in vitro. STLC could mediate cell apoptosis, as well as cell cycle
arrest, in a dose-dependent manner, which may contribute toward its antitumor
activity. STLC-mediated apoptosis and cell cycle arrest were triggered by
activation of the mitogen-activated protein kinase and nuclear factor kB
signaling pathways. These results suggested that STLC may have potential in the
in vivo treatment of neuroblastoma.
PMID- 29963179
TI - Safety markers for rhabdomyosarcoma cells using an in vivo imaging system.
AB - In vivo imaging system (IVIS) is a novel and rapidly expanding technology that is
widely applied in life sciences, including cell tracing. IVIS is able to quantify
biological events, including tumor proliferation, through counting the number of
photons emitted from a specimen. PLA802-enhanced green fluorescent protein
(EGFP), PLA802-monomeric cherry fluorescent protein (mCherry), RH30-EGFP and RH30
mCherry tumor cells were injected into 18 BALB/c female nude mice subcutaneously
with 5*106 cells in 100 ul to quantitatively analyze EGFP and mCherry cells
traced by IVIS. Inversion fluorescence microscopy revealed no transfection
efficiency difference between PLA802-EGFP (95.3+/-1.2%) and PLA802-mCherry
(95.8+/-1.7%), or between RH30-EGFP (94.7+/-2.1%) and RH30-mCherry (95.2+/-1.9%).
Transfection did not influence the cell morphology of PLA802 or RH30. The cell
migration, invasion and proliferation assay results of lentivirus-EGFP and
lentivirus-mCherry revealed no significant difference prior to or following
transfection. Therefore, lentivirus-EGFP and lentivirus-mCherry may serve as
safety biological markers for PLA802 and RH30 cells. In vivo experiments
demonstrated that lentivirus-EGFP and lentivirus-mCherry tumor luminescence
signals were observed in all mice by IVIS. Hematoxylin-eosin staining and
immunohistochemistry indicated that PLA802-EGFP, PLA802-mCherry, RH30-EGFP and
RH30-mCherry cell lines exhibited rhabdomyosarcoma (RMS) characteristics like the
maternal cells. In summary, mCherry and green fluorescent protein in human RMS
PLA802 and RH30 cancer cells may be safely and stably expressed for a long time
in vitro and in vivo.
PMID- 29963180
TI - PCDHGA12 methylation biomarker in bronchial washing specimens as an adjunctive
diagnostic tool to bronchoscopy in lung cancer.
AB - The use of bronchoscopy is central to the diagnosis of lung cancer. However, the
sensitivity of bronchoscopy is low. In addition, bronchial washing cytology,
which is a routine adjunctive test, does not significantly improve the
performance of bronchoscopy owing to its low sensitivity. To enhance the
diagnostic performance of bronchoscopy, the protocadherin GA12 (PCDHGA12)
methylation biomarker in bronchial washings was introduced as a novel adjunctive
diagnostic test. A total of 98 patients who underwent bronchoscopy owing to
suspicion of lung cancer were analyzed. Cytological examination and PCDHGA12
methylation biomarker testing of the bronchial washing fluid were performed. The
performance of the tests was analyzed. The final diagnosis in 60 patients was
lung cancer and in 38 patients was benign disease. The PCDHGA12 methylation
biomarker had a sensitivity of 75.0%, a specificity of 78.9% and a positive
predictive value (PPV) of 84.9%, whereas cytological assessment had a sensitivity
of 45.0%, a specificity of 92.1% and a PPV of 90%. Patients with positive
PCDHGA12 methylation test had an odds ratio for lung cancer of 11.25 (confidence
interval, 4.25-29.8) compared with negative subjects. The combination of the two
tests exhibited an increased sensitivity (83.3%), a specificity of 71.1% and a
PPV of 82.0%. Furthermore, considering the non-diagnostic bronchoscopy group
alone, the test demonstrated a sensitivity of 61.9% and a specificity of 78.9%.
The results of the present study demonstrated that PCDHGA12 methylation, as a
lung cancer biomarker in bronchial washings, may be a used as an adjunctive test
to bronchoscopy.
PMID- 29963181
TI - Gastrointestinal perforation during treatment with erlotinib plus bevacizumab in
two patients with non-small cell lung cancer exhibiting epidermal growth factor
receptor mutations: A case report.
AB - A previous randomized phase II study in patients with non-small cell lung cancer
(NSCLC) identified that combination treatment with erlotinib plus bevacizumab
prolonged progression-free survival compared with erlotinib alone. However,
combination bevacizumab and erlotinib treatment generally increased the risk of
severe adverse events, including hemorrhage, thrombosis, fistula formation and
gastrointestinal perforation. The present report describes two patients with
NSCLC harboring epidermal growth factor receptor (EGFR) mutations, who
experienced gastrointestinal perforation associated with erlotinib plus
bevacizumab combination therapy. The first patient, a 67-year-old male with stage
IIIB lung adenocarcinoma harboring a L858R point mutation in EGFR exon 21,
received concurrent chemoradiotherapy. However, seven months later, the patient
experienced a relapse and was administered erlotinib plus bevacizumab treatment.
A total of two months subsequent to commencing treatment, the patient developed a
perforated duodenal ulcer. The second patient, a 66-year-old male with lung
adenocarcinoma harboring a deletion in EGFR exon 19 and multiple pulmonary
metastases, demonstrated a partial response to erlotinib plus bevacizumab
treatment. A total of seven months subsequent to starting treatment, the patient
experienced lower abdominal pain, and abdominal computed tomography confirmed a
diagnosis of colocutaneous fistula complicating sigmoid diverticulitis. Following
repair of the perforation, both patients were restarted on erlotinib treatment
alone. Gastrointestinal perforation may be a potentially severe adverse event of
erlotinib plus bevacizumab combination therapy, even in the absence of tumor
metastasis in the abdomen.
PMID- 29963182
TI - Overexpression of 14-3-3zeta in lung tissue predicts an improved outcome in
patients with lung adenocarcinoma.
AB - One of the factors limiting the survival rate of patients with lung cancer is the
high risk for recurrence following surgical resection. Previous studies indicate
that 14-3-3zeta is a central cellular hub protein that regulates multiple
signaling pathways involved in cancer progression. The present study evaluated
the prognostic significance of 14-3-3zeta in patients with lung adenocarcinoma.
The expression of 14-3-3zeta and E-cadherin, an important protein involved in the
epithelial-mesenchymal transition, was evaluated by immunohistochemistry in lung
tumor tissues and adjacent normal lung tissues resected from 123 patients with
lung adenocarcinoma. The correlation between the two proteins, their association
with clinicopathological features and their prognostic significance were
subsequently analyzed. Within these parameters, an overall survival (OS)
prediction model was constructed using multivariate Cox proportional hazards
regression. The expression of 14-3-3zeta was upregulated in lung adenocarcinoma,
in contrast to E-cadherin, which was downregulated in lung adenocarcinoma tissues
compared with normal tissues. In addition, the expression of 14-3-3zeta was
positively correlated with that of E-cadherin (r=0.256, P=0.012) and
differentiation (P<0.001). Increased E-cadherin expression was indicative of
smaller tumor size and greater differentiation, and the overexpression of 14-3
3zeta and E-cadherin were associated with longer OS (P=0.010 and P=0.006,
respectively). Finally, a multivariate analysis revealed that TNM stage and 14-3
3zeta were independent prognostic indicators (P<0.001 and P=0.026, respectively).
14-3-3zeta may function as a tumor suppressor associated with E-cadherin
upregulation and could be used as a prognostic biomarker for resected lung
adenocarcinoma. These findings provide a novel insight on potential intervention
strategies for patients with lung cancer.
PMID- 29963183
TI - Downregulated Tim-3 expression is responsible for the incidence and development
of colorectal cancer.
AB - The present study aimed to investigate the role of T cell immunoglobulin domain
and mucin-3 (Tim-3) in its gene and protein forms in colorectal cancer (CRC), and
to verify the significance of Tim-3 expression in patients with CRC. A
prospective analysis of 258 patients with CRC and 246 normal controls was
conducted between December 2012 and June 2015. Intestinal samples were collected,
including of CRC tissues, paracancerous tissues and normal colon mucosa tissues.
Peripheral venous blood samples were also collected. Polymerase chain reaction
(PCR) amplification, reverse transcription-quantitative PCR (RT-qPCR) and western
blot analysis was performed for the detection and evaluation of Tim-3 gene and
protein in various tissues. PCR analysis indicated that the T and G alleles of
882C/T and 4259T/G are associated with a significantly increased risk of CRC.
Following the confirmation of Tim-3 expression in CRC tissues, RT-qPCR detection
and western blot analysis revealed clear downregulation of Tim-3 mRNA and protein
expression in the blood and tissue samples obtained from patients with CRC, as
compared with in the corresponding control samples. Similar trends of decreased
Tim-3 mRNA levels and protein expression were observed in CRC tissues compared
with in the paracancerous and the normal colon mucosa tissues. In addition, the
mRNA and protein expression levels in the paracancerous tissues were lower than
those in the normal colon mucosa tissues. Furthermore, significantly lower Tim-3
mRNA levels were observed in patients with a tumor size >5 cm, a poor
differentiation degree, higher tumor-node-metastasis stage (stage III-IV), and
lymph node and distant metastasis. Collectively, genetic changes to Tim-3,
expressed as polymorphisms in Tim-3, and decreased mRNA/protein expression may be
partially responsible for the incidence and development of CRC.
PMID- 29963185
TI - Associations between CA19-9 and CA125 levels and human epidermal growth factor
receptor 2 overexpression in patients with gastric cancer.
AB - The aim of the present study was to investigate the association between serum
carbohydrate antigen (CA)19-9 and CA125 levels, and human epidermal growth factor
receptor 2 (HER2) expression in patients with gastric cancer, as well as to
identify any correlation between them and the risk of recurrence and metastasis.
A total of 256 patients were enrolled in the present study, and 219 patients were
followed-up to investigate recurrence and metastasis of gastric cancer.
Immunohistochemistry was used to detect HER-2 in gastric adenocarcinoma and
paracancerous tissues. The positive rate of CA19-9 and CA125 in stages III/IV was
higher compared with that in stages I/II. The positive rate of HER2 in distinct
stages of gastric cancer was not statistically different. Serum CA19-9 and CA125
were not associated with the positive expression of HER2. The recurrence and
metastasis of CA19-9, CA125 and HER2-positive gastric cancer were increased
compared with those experienced by CA19-9, CA125 and HER2-negative patients. Age,
stage and preoperative tumor markers were associated with 3-year prognosis of
gastric cancer. HER2 [odds ratio (OR)=2.55] and CA19-9 (OR=1.22) were independent
prognostic factors in patients with gastric cancer. CA19-9, CA125 and HER2 may be
used to predict the recurrence or metastasis of gastric cancer. The combined
detection may be able to improve the sensitivity and efficiency of predicting the
recurrence or metastasis of gastric cancer. Preoperative positive serum for CA19
9 and CA125 were associated with poor prognosis in patients with gastric cancer.
CA19-9 and HER2 were independent prognostic factors of gastric cancer.
PMID- 29963184
TI - Overexpression of the matrix metalloproteinase 11 gene is a potential biomarker
for type 1 endometrial cancer.
AB - Metalloproteinase matrix 11 (MMP11) is a member of the matrix metalloproteinase
family, which are able to degrade extracellular matrix components, and may serve
a central function in the enhancement of tumor-induced angiogenesis, cell
migration, proliferation, apoptosis and connective tissue degradation. In the
present study, MMP11 gene expression was investigated using the reverse
transcription-polymerase chain reaction in 68 cases of type I endometrial
carcinoma, and all data were analyzed in association with clinical
characteristics. Overexpression of MMP11 was demonstrated in 75%, and sub
expression was demonstrated in 25%, of endometrial cancer cases. Sub-expression
cases were associated with good histological parameters, including low
histological grade (G1 and G2), early pathological stage, and absence of vascular
invasion, metastasis and recurrence. In total, 76.4% of endometrial cancer cases
with sub-expression were identified as early stage 1A and B; however, 23.6% of
cases were identified as stage 2, with vascular invasion present in 29.4% of
cases. On the other hand, cases which demonstrated overexpression with high
ranges (>10 times more than control) were associated with adverse
histopathological characteristics, including high grade tumor (G3) and vascular
invasion. In conclusion, the increased expression of MMP11 may be used as a
prognostic biomarker in patients with type 1 endometrial cancer.
PMID- 29963186
TI - Overexpression of mRNA-decapping enzyme 1a affects survival rate in colorectal
carcinoma.
AB - Processing bodies (P-bodies) are one of the most well understood types of RNA
granules, and are associated with a variety of diseases, including cancer. mRNA
decapping enzyme 1a (DCP1a), which may be used as a marker to analyze P-bodies,
participates in the removal of the 5'-methylguanosine cap from eukaryotic mRNAs
as a cofactor. The aim of the present study was to analyze the association
between DCP1a expression and clinical features in colorectal carcinoma (CRC). The
levels of DCP1a mRNA expression were detected by reverse transcription
quantitative polymerase chain reaction assay in carcinoma and non-carcinoma
tissues from 75 patients, while the protein expression levels were evaluated by
immunohistochemistry and western blotting. Additional associations between DCP1a
expression and clinical characteristics were analyzed by chi2 test and Cox
regression analysis. In the 75 cases, the levels of DCP1a mRNA and protein
expression were increased in colorectal carcinoma tissues compared with non
carcinoma tissues. A high expression of DCP1a was significantly associated with
lower survival rates in patients with CRC compared with patients with low DCP1a
expression (P=0.001). Associations with depth of invasion (P=0.008), lymph node
metastasis (P=0.001) and tumor node metastasis stage (P=0.001) were also
observed. Additional Cox regression analysis revealed that the DCP1a expression
(P=0.012) is an independent factor in survival rate. It was also identified that
DCP1a may have high expression in colorectal carcinoma tissues and be associated
with poor prognosis. This suggests that DCP1a may be a diagnostic marker or
prognostic indicator to assist with patient assessments and therapies.
PMID- 29963187
TI - ILK promotes angiogenic activity of mesenchymal stem cells in multiple myeloma.
AB - Angiogenic activity in solid tumors has been demonstrated to promote metastasis
through the activation of certain proteins involved in the epithelial-mesenchymal
transition-associated process. The molecular mechanism underlying multiple
myeloma-induced angiogenesis involves angiogenic cytokines by plasma cells as
well as their induction within the microenvironment. Integrin-linked kinase (ILK)
is a highly evolutionarily conserved intracellular protein that was originally
identified as an integrin-interacting protein, and extensive genetic and
biochemical studies have identified ILK expression to be vital during tumor
driven angiogenesis. In the present study, it was identified that angiogenic
factors were upregulated in mesenchymal stem cells (MSCs) that were co-cultured
with multiple myeloma cell lines. It was also revealed that upregulated ILK
expression significantly promoted the capillary-formation ability of MSCs. The
concentrations of angiogenic factors were significantly decreased compared with
non-targeting siRNA-transfected and control MSCs. MSCs may participate in
inducing the angiogenic response in multiple myeloma depending on ILK expression.
PMID- 29963188
TI - Effects of endometrial stem cell transplantation combined with estrogen in the
repair of endometrial injury.
AB - The present study investigated the effects of endometrial stem cell (EnSCs)
transplantation combined with estrogen in the repair of endometrial injury. A
total of 30 patients with intrauterine adhesions (IUA) and 30 healthy individuals
were selected. Expression of epidermal growth factor (EGF) and platelet-derived
growth factor (PDGF)-BB in endometrial tissue was assessed. Additionally,
expression levels of epithelial membrane antigen (EMA), cytokeratin (CK),
integrin alpha-6 (CD49f), Thy-1 membrane glycoprotein (THY-1), collagen type 1
(Col I), fibroblast (5B5) and vimentin in EnSCs were detected using western blot
analysis and reverse transcription-quantitative polymerase chain reaction. A rat
model of IUA was established and female rats were divided into the control,
model, EnSCs, estrogen and estrogen plus EnSCs (E+EnSCs) groups. Blood was
extracted at 1 and 5 weeks post-treatment, and serum levels of transforming
growth factor (TGF)-beta1, EGF, 17 beta-estradiol (E2) and PDGF-BB were measured
using ELISA. Hematoxylin and eosin staining was performed to observe the
pathological changes of endometrial tissue in rats. Western blot analysis was
used to detect the expression of estrogen receptor (ESR1) and matrix
metalloproteinase (MMP)-9 in the endometrium. The results revealed that patients
with IUA exhibited increased expression levels of EGF and PDGF-BB compared with
those in control group. Additionally, EnSCs exhibited significantly increased
expression levels of EMA, CD49f, CK, Col I, THY-1, 5B5 and vimentin compared with
the remaining groups. An increased number of newly formed glands was observed in
the E+EnSCs group compared with that in the EnSCs group. Increased levels of E2,
but decreased levels of TGF-beta1, EGF, PDGF-BB, ESR1 and MMP-9 were detected in
EnSCs and estrogen groups compared with those in E+EnSCs group. These results
suggest that EnSCs transplantation combined with estrogen could improve
endometrial abnormalities.
PMID- 29963189
TI - Expression of CD44, CD44v9, ABCG2, CD24, Bmi-1 and ALDH1 in stage I and II oral
squamous cell carcinoma and their association with clinicopathological factors.
AB - Cancer stem cells (CSCs) exhibit self-replication, self-differentiation, drug
resistance and immune evasion activities. In recent years CSCs have become
increasingly important for the treatment of malignant tumors. CSCs express
specific markers, including cluster of differentiation (CD)44, CD44 variant 9
(CD44v9), ATP-binding cassette sub-family G member 2 (ABCG2), CD24, B lymphoma Mo
MLV insertion region 1 homolog (BMI-1) and aldehyde dehydrogenase 1 (ALDH1).
However, the prognostic value of their expression in patients with oral squamous
cell carcinoma (OSCC) are not well known. The present study evaluated these
markers in stage I and II patients with OSCC and examined the association between
T classification, histological differentiation, classification of invasion mode,
lymph node metastasis and disease-free survival rate. Tissue specimens were
obtained from 70 patients with stage I or II OSCC following either surgery or
biopsy. Immunohistochemistry was performed and positive staining was defiend as
10% positive cells. CD44 and CD44v9 expressions were strongly detected in all
OSCC tissues compared with normal epithelial cells. A total of 22 (31.4%) cases
expressed ABCG2 and there was a significant association between ABCG2 expression
and invasion. A total of 41 cases (59.0%) expressed CD24 and there was a
significant association between CD24 expression and invasion. A total of 33 cases
(47.1%) expressed BMI-1 and there was a significant association between BMI-1
expression and the disease-free survival rate. A total of 18 cases (25.7%)
expressed ALDH1. Although there was no association between ALDH1 expression and T
classification, there were significant associations between ALDH1 expression and
histological differentiation, invasion mode, metastasis and the disease-free
survival rate. Multivariate analysis revealed that ALDH1 expression was the only
prognostic factor for disease-free survival rate. The results of the present
study suggest that the positivity of ALDH1 detected in patients with OSCC
correlates with the number of cells undergoing epithelial mesenchymal transition
and metastasis. These findings indicated that the expression of ALDH1 may be an
effective prognostic marker indicating the survival of patients with stage I and
II OSCC.
PMID- 29963190
TI - miR-202 acts as a potential tumor suppressor in breast cancer.
AB - Breast cancer affects ~10% of women worldwide and is responsible for ~12% of all
cancer-associated mortalities. Breast cancer is more prone to metastasis compared
with other types of cancer. Up to 5% of patients with breast cancer present with
incurable metastasis and an additional 10-15% of patients develop metastases
within 3 years of their initial diagnosis. MicroRNAs (miRNAs) are short RNAs, 21
25 nucleotides in length, that have been shown to significantly affect gene
expression. In total >2,000 miRNAs have been identified and specific miRNAs have
been revealed to be associated with cancer. In the present study, we observed
that the majority of breast cancer specimens collected expressed low levels of
miR-202 compared with adjacent tissues and normal cell lines. Mechanistic
investigations identified KRAS as a potential target gene of miR-202 and it was
demonstrated that miR-202 exerted its tumor-suppressive effects by regulating the
expression of KRAS in breast cancer cells. Functional assays revealed that miR
202 significantly reduced cell proliferation, migration and invasion in vitro. In
summary, these results indicate the function of miR-202 in breast cancer
progression and suggest that its use within breast cancer therapy is promising.
PMID- 29963191
TI - Wnt6 contributes tumorigenesis and development of colon cancer via its effects on
cell proliferation, apoptosis, cell-cycle and migration.
AB - Wnt proteins have been reported to contribute to the progression of various types
of cancer. Wnt6 is a member of the Wnt family and may promote tumorigenesis in
gastrointestinal cancer and cervical cancer. In the present study, the expression
of Wnt6 in human colon cancer cell lines was evaluated, in order to investigate
the role of Wnt6 in the development of colon cancer. Additionally, the effects of
Wnt6 upregulation or downregulation on proliferation, apoptosis, cell cycle and
cell migration of colon cancer cells have been investigated. Furthermore, western
blot analysis was employed to evaluate the expression of Wnt6, B-cell lymphoma 2
associated X protein (Bax), caspase-3 and matrix metalloproteinase (MMP)2. The
results of the present study demonstrated that the expression of Wnt6 was
increased in HCT116 and SW480 cells compared with the remaining colon cancer cell
lines. Furthermore, overexpression Wnt6 resulting from transfection of
pGPU6/GFP/Neo-Wnt6-Homo-1 plasmid promoted the proliferation, cell cycle and
migration of HCT116 and SW480 cells, but inhibited cell apoptosis in vitro. The
expression of caspase-3 and MMP2 was increased, whereas the expression of Bax was
decreased in response to upregulation of Wnt6. These results suggested that Wnt6
may serve a vital function in the development of colon cancer.
PMID- 29963192
TI - Absent expression of miR-30a promotes the growth of lung cancer cells by
targeting MEF2D.
AB - The microRNA (miR)-30 family has been reported to be aberrantly expressed in
several types of cancer. However, its contributions to lung cancer remain to be
fully elucidated. Myocyte enhancer factor 2D (MEF2D), an oncogene in liver
cancer, has been shown to be aberrantly expressed in lung cancer. In the present
study, it was found that MEF2D and miR-30a were inversely correlated in lung
cancer samples. Using an online database, it was predicted that miR-30a targeted
the 3' untranslated region (UTR) of MEF2D mRNA. The activity of luciferase with
MEF2D 3'UTR was suppressed by transfecting cells with miR-30a mimics. The results
of western blot analysis showed that the miR-30a mimics also suppressed the MEF2D
protein. The miR-30a mimics were able to reduce the growth and colonies of lung
cancer cells by suppressing MEF2D. The results of FACS and western blot assays
showed that the apoptotic rate was reduced by transfection with the miR-30a
mimics. Collectively, the aberrant expression of miR-30a in lung cancer promoted
the expression of MEF2D protein. miR-30a inhibited the growth and colony
formation of the lung cancer cells by promoting apoptosis.
PMID- 29963193
TI - Upregulation of lncRNA Sox2ot indicates a poor prognosis for patients with
hepatocellular carcinoma and promotes cell invasion.
AB - Long non-coding RNA Sox2 overlapping transcript (lncRNA Sox2ot) expression has
been demonstrated to be upregulated in a number of types of tumor, and may act as
an oncogene. The present study aimed to evaluate the clinical role of lncRNA
Sox2ot and its association with the epithelial-mesenchymal transition in
hepatocellular carcinoma (HCC). Reverse transcription-quantitative polymerase
chain reaction (RT-qPCR) was performed to determine the expression of lncRNA
Sox2ot in 86 cases of HCC tissues and adjacent non-tumor tissues. Kaplan-Meier
and log-rank test was used to analyze the association between lncRNA Sox2ot
expression and disease-free (DFS) or overall (OS) survival time. In addition, the
capacity of HCC cells with lncRNA Sox2ot knockdown for invasion was evaluated via
transwell cell invasion assays. RT-qPCR and western blot analyses were also
performed to determine the mRNA and protein expression of Twist1, E-cadherin and
N-cadherin in the HCC cells. It was indicated that lncRNA Sox2ot expression
levels were significantly higher in HCC tissues compared with adjacent non-tumor
tissues. Increased expression levels of lncRNA Sox2ot were associated with the
tumor size, the tumor number and vein invasion in patients with HCC. An
association was observed between lncRNA Sox2ot and the DFS and OS of patients
with HCC. Furthermore, it was determined that cell invasion was inhibited
following the siRNA knockdown of lncRNA Sox2ot in MHCC97H and SMCC-7721 cells via
transwell cell invasion assays. Furthermore, it was demonstrated that knockdown
of lncRNA Sox2ot downregulated the mRNA and protein expression of Twist1 and N
cadherin, but upregulated the E-cadherin expression levels in MHCC97H and SMCC
7721 cells. Thus, it was indicated that lncRNA Sox2ot may be a novel predictive
biomarker and a potential therapeutic target for HCC.
PMID- 29963194
TI - Clinical evaluation of 4 types of microRNA in serum as biomarkers of esophageal
squamous cell carcinoma.
AB - To the best of our knowledge, there is currently no specific biomarker for
esophageal cancer used in clinical practice. However, studies consider that
microRNAs (miRNAs/miRs) could have useful implications in clinical practice. The
present study aimed to investigate the feasibility of using serum microRNAs as
biomarkers for esophageal squamous cell carcinoma (ESCC). Using reverse
transcription-quantitative polymerase chain reaction, the expression levels of
serum miR-21, miR-25, miR-145 and miR-203 were detected in 31 untreated patients
with ESCC (EC-UT), 35 inactive period patients with ESCC following treatment (EC
T), 33 patients with esophageal benign disease (benign) and 32 healthy donors
(healthy). Furthermore, the ability of these microRNAs to function as biomarkers
of ESCC alone and in combination were investigated. The expression levels of
serum miR-21, miR-25 and miR-145 in EC-UT were significantly higher than in the
other groups (P<0.001). High sensitivity and specificity were shown when miRNAs
were used as biomarkers for ESCC, particularly miR-21 and the combination of miR
21 with miR-145. Comparing EC-UT with healthy, benign and EC-T groups, and a
combined group (3 groups set as 1 negative control), the sensitivity and
specificity of miR-21 were 71.0 and 96.9, 74.2 and 87.9, 77.4 and 82.9, and 74.2
and 88.0%, respectively. The combined sensitivity and specificity of miR-21 and
miR-145 were 71.0 and 96.9, 90.9 and 72.7, 97.1 and 82.9, and 80.6 and 80.0%,
respectively. In conclusion, 3 types of miRNA (miR-21, miR-25 and miR-145) in
serum could serve as potential biomarkers for ESCC. Furthermore, the expression
level of miR-145 in serum was upregulated, compared with the downregulation
reported in previous studies in ESCC tissues and cells.
PMID- 29963195
TI - Analysis of the complex interaction of CDR1as-miRNA-protein and detection of its
novel role in melanoma.
AB - Despite improvements in the prevention, diagnosis and treatment of melanoma
having developed rapidly, the role of circular RNA CDR1 antisense RNA (CDR1as) in
melanoma remains to be elucidated. The aim of the present study was to predict
the novel roles of CDR1as in melanoma through novel bioinformatics analysis. In
the present study, the circ2Traits database was used to supply information on
CDR1as in cancer. CircNet, circBase and circInteractome databases were used to
detect the co-expression of CDR1as, microRNAs and proteins. Furthermore, the
functions and pathways of the associated proteins were predicted using the
Database for Annotation, Visualization and Integrated Discovery. Gene Ontology
enrichment analysis suggested that the proteins associated with CDR1as were
mainly regulated in the cytoplasm as the molecular protein binding, the
biological process of cell division and the endoplasmic reticulum tubular
network, which are all involved in cancer-related processes. The Kyoto
Encyclopedia of Genes and Genome pathway cell cycle was closely associated with
the location of cancer. Co-expression network analysis revealed the associations
among CDR1as, microRNAs and proteins. The bioinformatics analysis showed that
CDR1as may act as the competing endogenous RNA for the vital genes, which are
associated with the invasion and migration of melanoma.
PMID- 29963196
TI - Presence of cancer cells in the periarterial tissues of patients with advanced
gastric cancer.
AB - Lymphadenectomy with gastrectomy is considered a curative surgical treatment for
gastric cancer. Periarterial connective tissue-preserving lymphadenectomy has
become a common procedure following developments in laparoscopic surgery.
However, the presence of cancer cells in the periarterial tissue, including
neural invasion, has not been examined. In the present study, the periarterial
tissues from the vessel roots of the left gastric artery (LGA) and right
gastroepiploic artery (RGEA) after gastrectomy were evaluated for the presence of
cancer cells. The study included 28 consecutive patients who underwent
gastrectomy for gastric cancer. The vessel roots of the RGEA and LGA were
obtained from surgically resected specimens and examined by two independent
pathologists to determine the presence of cancer cells in the periarterial
tissues. The collected specimens included 23 RGEA roots and 26 LGA roots from 28
patients. In 8 cases of early gastric cancer, no cancer cells were indicated in
the periarterial tissues. By contrast, cancer cells, including neural invasion in
2 cases, were identified in the periarterial tissues from the roots of examined
gastric arteries in 3/20 (15%) cases of advanced gastric cancer. Notably, all 3
cases featured multiple regional lymph node (LN) metastases. Cancer cells were
detected in the perivascular tissue of the major gastric arteries from cases with
advanced gastric cancer with LN metastases, suggesting the requirement for
oncologic evaluation to ensure adequate vascular tissue margins and an adequate
periarterial layer during lymphadenectomy.
PMID- 29963197
TI - MicroRNA-599 suppresses glioma progression by targeting RAB27B.
AB - MicroRNAs (miRNAs/miRs) serve tumor promoting or suppressive roles in different
human cancer types, including glioma; however, the regulatory underlying
mechanism by which miR-599 affects glioma progression remains largely unknown.
The aim of the present study was to investigate the expression of miR-599 in
glioma, as well as the underlying regulatory mechanism. Reverse transcription
quantitative polymerase chain reaction and western blot analysis were used to
examine mRNA and protein expression, respectively. MTT, wound healing and
transwell assays were conducted to study cell proliferation, migration and
invasion, respectively. A dual-luciferase reporter gene assay was used to confirm
the targeting association between miR-599 and Ras-related protein Rab-27B
(hereafter RAB27B). In the present study, miR-599 expression was observed to be
significantly downregulated in human glioma tissues and cell lines, when compared
with normal brain tissues and normal human astrocyte cells, respectively. Low miR
599 expression was significantly associated with glioma progression. Ectopic
expression of miR-599 caused a significant reduction in the proliferation,
migration and invasion of U-87MG Uppsala and U251 cells. Bioinformatics analysis
and dual-luciferase reporter gene assay data identified that RAB27B was a direct
target gene of miR-599. The mRNA and protein expression of RAB27B was
significantly downregulated following miR-599 overexpression in U-87MG Uppsala
and U251 cells. Rescue experiments demonstrated that RAB27B rescued the miR-599
induced inhibition of glioma cell growth, migration and invasion. In addition,
RAB27B expression was significantly upregulated in glioma tissues and cell lines,
and the expression levels of RAB27B were inversely correlated with miR-599 levels
in glioma tissues; therefore, the present study demonstrated that miR-599 exerts
a tumor-suppressive role in glioma progression by targeting RAB27B, indicating
that miR-599 may be used as a potential candidate for glioma treatment.
PMID- 29963198
TI - Prognostic value of glypican-1 for patients with advanced pancreatic cancer
following regional intra-arterial chemotherapy.
AB - Regional intra-arterial chemotherapy (RIAC) is a potential alternative treatment
for advanced pancreatic cancer (APC) with fewer adverse effects than other
treatment options. However, specific biomarkers to determine the prognosis of
patients with APC have thus far, been unsatisfactory. Glypican-1 (GPC1) in
exosomes has been identified as an early diagnostic biomarker for pancreatic
adenocarcinoma. The aim of the present study was to investigate whether the
presence of GPC1 in extracellular vesicles (EVs) could serve as a predictor of
RIAC outcome for patients with APC. EVs in circulation were isolated and the
percentage of GPC1+ EVs was measured using flow cytometry. Compared with healthy
individuals, the levels of GPC1+ EVs were significantly increased in patients
with APC (P<0.01). Following RIAC treatment, the percentage of GPC1+ EVs was
decreased (P=0.023). Furthermore, patients with APC exhibiting a greater decrease
of GPC1+ EVs experienced improved overall survival (OS) rates. In summary, the
present study provides insights into identifying GPC1 as a novel prognostic
biomarker for patients with APC following RIAC treatment.
PMID- 29963200
TI - Liver kinase B1/adenosine monophosphate-activated protein kinase signaling axis
induces p21/WAF1 expression in a p53-dependent manner.
AB - Liver kinase B1 (LKB1) encodes a serine/threonine kinase and functions as a tumor
suppressor. LKB1 loss-of-function somatic mutations are frequently observed in
sporadic types of cancer, particularly in lung cancer. Ectopic LKB1 induces
growth arrest by upregulating p21/cyclin dependent kinase inhibitor 1A (WAF1) in
LKB1 deficient cervical and melanoma cancer cell lines. However, the underlying
molecular mechanism remains to be elucidated. The present study built upon
previous observations by confirming that the ectopic expression level of LKB1
significantly reduced colony formation of LKB1-deficient lung cancer cells.
Mechanistically, the present study demonstrated that LKB1 overexpression
significantly induced p21/WAF1 expression in a kinase-dependent manner.
Conversely, LKB1 stable knockdown resulted in a decrease in p21/WAF1 expression
level in colon cancer cells. In addition, it was revealed that pharmacological
activation of adenosine monophosphate protein kinase (AMPK) by 2-deoxyglucose
significantly increased the p21/WAF1 expression level, suggesting that AMPK acts
downstream of LKB1 to induce p21/WAF1 expression. Furthermore, the present study
demonstrated that functional p53 was required for p21/WAF1 induction by LKB1.
Phosphorylation of p53-Ser15 was increased by ectopic LKB1 or AMPK activation.
Taken together, these results suggested that LKB1 acts via its substrate, AMPK,
to upregulate p21/WAF1 expression in a p53-dependent manner. Therefore, the
present study identified an important signaling axis, providing novel molecular
insights into the tumor suppressor role of LKB1.
PMID- 29963199
TI - A HER2 bispecific antibody can be efficiently expressed in Escherichia coli with
potent cytotoxicity.
AB - Bispecific antibodies have been actively studied for cancer therapy due to their
potent cytotoxicity against tumor cells. A number of bispecific antibody formats
have exhibited strong tumor cytotoxicity in vitro and in vivo. However, effective
production of bispecific antibodies remains challenging for the majority of
bispecific antibody formats. In the present study, a bispecific antibody was
designed that links a conventional antigen-binding fragment (Fab) against cluster
of differentiation 3 antigen (CD3) to a camel single domain antibody (VHH)
against human epidermal growth factor receptor 2 (HER2). This bispecific antibody
may be secreted and purified efficiently from Escherichia coli culture medium.
The purified bispecific antibody is able to trigger T cell-mediated HER2-specific
cytotoxicity in vitro and in vivo. The data gathered in the present study suggest
that this bispecific format may be applied to other tumor antigens to produce
bispecific antibodies more efficiently.
PMID- 29963201
TI - Pilot study of WT1 peptide-pulsed dendritic cell vaccination with docetaxel in
esophageal cancer.
AB - In the present study, the immune response to Wilms tumor gene 1 (WT1) peptide
pulsed dendritic cell (DC) vaccination combined with docetaxel (DCDOC) in
advanced esophageal cancer patients who had already received first-line
chemotherapy was investigated. Ten HLA-A*2402 patients were treated with
docetaxel (50 mg/m2) on day 1 and WT1 peptide-pulsed DC vaccination (1*107 cells)
on days 15 and 22 (repeated every 4 weeks for 3 cycles). The delayed-type
hypersensitivity skin test, HLA tetramer assay and interferon-gamma enzyme-linked
immunospot (ELISPOT) assay were used to evaluate the induction of a WT1-specific
immune response. Median overall survival was 5 months (range, 1.1-11.6). The
clinical effect of DCDOC therapy was not observed and only 1 patient could
complete the protocol therapy. Disease progression was observed in 9 patients and
1 patient succumbed to fatality during the second cycle of therapy. As a pilot
study, it was not possible to evaluate the safety of WT1 peptide-pulsed DCDOC
therapy for esophageal squamous cell cancer. However, a WT1-specific response in
6 patients, as indicated by the ELISPOT or HLA/WT1-tetramer assay, was
demonstrated. The results suggested that the positive immune response had
significant relevance on the low percentage of CD11b+ and CD66b+ granulocytic
myeloid-derived suppressor cells in CD15+ cells. Furthermore, DCDOC elicited a
WT1-specific immune response regardless of the myelosuppression associated with
docetaxel. The present findings support future studies and further work to assess
DCDOC as an adjuvant therapy for esophageal cancer will be performed. The present
clinical trial was registered in the University Hospital Medical Information
Network (UMIN) Clinical Trials Registry on November 11th, 2011, no.
UMIN000006704.
PMID- 29963202
TI - Rapid detection of tert-butoxycarbonyl-methamphetamine by direct analysis in real
time time-of-flight mass spectrometry.
AB - Purpose: Phenethylamines constitute the majority of drug-related arrests in
Japan. Recently, the smuggling of tert-butoxycarbonyl (t-Boc)-protected
phenethylamines has become of increasing concern, because of the difficult
identification of these masked substances. Methods: In this study, a rapid and
accurate method for the detection of t-Boc-methamphetamine (t-Boc-MP) by direct
analysis in real time-time-of-flight-mass spectrometry (DART-TOF-MS) was
developed. The efficiency of the method was evaluated by comparison with
conventional gas chromatography-MS (GC-MS) and liquid chromatography-TOF-MS (LC
TOF-MS) techniques. Results: During GC-MS analysis of t-Boc-MP, MP was generated
in the injection port, which can lead to an analytical error. In the LC-TOF-MS
spectrum, fragment ions were detected, which were generated by McLafferty
rearrangement in the ion source. On the other hand, in the DART-TOF-MS analysis
of t-Boc-MP, pyrolysis could be suppressed by using a micro-syringe injection
method, and the fragment ions generated by McLafferty rearrangement were still
observed. Moreover, protonated t-Boc-MP could be detected. Conclusions: Hence,
DART-TOF-MS provides a rapid and accurate method for the detection of t-Boc-MP,
allowing suppression of the pyrolysis reaction and identification of both
fragment ions and protonated t-Boc-MP. To our knowledge, this is the first report
for detecting t-Boc-MP by MS techniques.
PMID- 29963203
TI - Simple screening procedure for 72 synthetic cannabinoids in whole blood by liquid
chromatography-tandem mass spectrometry.
AB - Purpose: In recent years, many synthetic cannabinoids (SCs) have appeared on the
drug market. Despite the increasing number of SCs, there are few comprehensive
screening methods for their detection in biological specimens. In this context,
the purpose of this study was to develop a fast and simple liquid chromatography
tandem mass spectrometry screening procedure for detection and identification of
SCs in whole blood. Methods: The elaborated qualitative screening method allows
the simultaneous detection and identification of 72 compounds from different
chemical groups: naphthoylindoles, naphthoylindazoles, benzoylindoles,
phenylacetylindoles, tetramethylcyclopropylindoles, indole-3-carboxylic acid
esters, indole-3-carboxylic acid amides, indazole-3-carboxylic acid amides, and
others. Whole-blood samples (0.2 mL) were precipitated with acetonitrile (0.6
mL). The separation was achieved with the gradient of the mobile phase
composition (0.1% formic acid in acetonitrile and 0.1% formic acid in water) and
the gradient of the flow rate (0.5-0.8 mL/min) in 16 min. Detection of all
compounds was based on dynamic multiple reaction monitoring. Results: Mass
spectrometer parameters for all compounds were presented. All of the compounds
were well-separated by their retention times and/or transitions. The limits of
detection (LODs) for 50 compounds were in the range 0.01-0.48 ng/mL. Conclusions:
Estimated LODs make this assay suitable for the analysis of biological material.
The procedure can be easily expanded for more substances, which is an
indispensable advantage in the dynamically developing drug market. It can have
wide application in various analytical forensic and clinical laboratories.
PMID- 29963204
TI - Effects of the new generation alpha-pyrrolidinophenones on spontaneous locomotor
activities in mice, and on extracellular dopamine and serotonin levels in the
mouse striatum.
AB - Purpose: Pyrovalerone derivatives (alpha-pyrrolidinophenones) form a distinct
branch of synthetic cathinones, a popular group of novel psychoactive substances,
and exert strong psychostimulatory effects resulting from their high potency to
inhibit dopamine (DA) and norepinephrine transporters, with negligible activity
at the serotonin (5-HT) transporter. In contrast to the old generation alpha
pyrrolidinophenones, 3,4-MDPV and alpha-PVP, there is limited data on the
pharmacology and toxicology of the novel analogs. Therefore, the present study
assesses the in vivo effects of two new pyrovalerones, PV8 and PV9, along with
those of alpha-PVP, on spontaneous locomotor activities of mice and extracellular
DA and 5-HT levels in the mouse striatum. Methods: Spontaneous locomotor activity
was measured using Opto-Varimex Auto-Track. Effects of tested compounds on
extracellular levels of DA and 5-HT in the striatum were studied by an in vivo
microdialysis technique; their concentrations in dialysate fractions were
analyzed by high-performance liquid chromatography with electrochemical
detection. Results: alpha-PVP, PV8 and PV9 stimulated mice locomotor activity (an
effect being blocked by D1-dopamine receptor antagonist, SCH 23390), and
increased extracellular levels of DA and 5-HT in the striatum. Observed effects
depend on dose, time and compound under investigation, with alpha-PVP being more
potent than PV8 and PV9. When used at the same dose, the pyrovalerones produced
effects significantly weaker than a model, old generation psychostimulant,
methamphetamine. Conclusions: Enhancement of dopaminergic neurotransmission plays
a dominant role in the psychomotor stimulation caused by alpha-PVP, PV8 and PV9.
Extending an aliphatic side chain beyond a certain point leads to the decrease in
their potency in vivo.
PMID- 29963205
TI - Differentiation of AB-FUBINACA and its five positional isomers using liquid
chromatography-electrospray ionization-linear ion trap mass spectrometry and
triple quadrupole mass spectrometry.
AB - Purpose: Positional isomer differentiation is crucial for forensic analysis. The
aim of this study was to differentiate AB-FUBINACA positional isomers using
liquid chromatography (LC)-electrospray ionization (ESI)-linear ion trap mass
spectrometry (LIT-MS) and LC-ESI-triple quadrupole mass spectrometry (QqQ-MS).
Methods: AB-FUBINACA, its two fluorine positional isomers on the phenyl ring, and
three methyl positional isomers in the carboxamide side chain were analyzed by LC
ESI-LIT-MS and LC-ESI-QqQ-MS. Results: Four of the positional isomers, excluding
AB-FUBINACA and its 3-fluorobenzyl isomer, were chromatographically separated on
an ODS column in isocratic mode. ESI-LIT-MS could discriminate only three
isomers, i.e., the 2-fluorobenzyl isomer, the N-(1-amino-2-methyl-1-oxobutan-2
yl) isomer, and the N-(1-amino-1-oxobutan-2-yl)-N-methyl isomer, based on their
characteristic product ions observed at the MS3 stage in negative mode. ESI-QqQ
MS differentiated all six isomers in terms of the relative abundances of the
product ions that contained the isomeric moieties involved in collision-induced
dissociation reactions. The six isomers were more clearly and significantly
differentiated upon comparison of the logarithmic values of the product ion
abundance ratios as a function of collision energy. Conclusions: The present LC
MS methodologies were useful for the differentiation of a series of AB-FUBINACA
positional isomers.
PMID- 29963206
TI - Chemical synthesis, characterisation and in vitro and in vivo metabolism of the
synthetic opioid MT-45 and its newly identified fluorinated analogue 2F-MT-45
with metabolite confirmation in urine samples from known drug users.
AB - Purpose: The detection of a novel psychoactive substance, 2F-MT-45, a fluorinated
analogue of the synthetic opioid MT-45, was reported in a single seized tablet.
MT-45, 2F-, 3F- and 4F-MT-45 were synthesised and reference analytical data were
reported. The in vitro and in vivo metabolisms of MT-45 and 2F-MT-45 were
investigated. Method: The reference standards and seized sample were
characterised using nuclear magnetic resonance spectroscopy, ultra-performance
liquid chromatography-quadrupole time of flight mass spectrometry, gas
chromatography-mass spectrometry, attenuated total reflectance-Fourier transform
infrared spectroscopy and Raman spectroscopy. Presumptive tests were performed
and physicochemical properties of the compounds determined. Metabolite
identification studies using human liver microsomes, human hepatocytes, mouse
hepatocytes and in vivo testing using mice were performed and identified MT-45
metabolites were confirmed in authentic human urine samples. Results: Metabolic
pathways identified for MT-45 and 2F-MT-45 were N-dealkylation, hydroxylation and
subsequent glucuronidation. The major MT-45 metabolites identified in human in
vitro studies and in authenticated human urine were phase I metabolites and
should be incorporated as analytical targets to existing toxicological screening
methods. Phase II glucuronidated metabolites were present in much lower
proportions. Conclusions: 2F-MT-45 has been detected in a seized tablet for the
first time. The metabolite identification data provide useful urinary metabolite
targets for forensic and clinical testing for MT-45 and allows screening of urine
for 2F-MT-45 and its major metabolites to determine its prevalence in case work.
PMID- 29963207
TI - Pharmacological evaluation of new constituents of "Spice": synthetic cannabinoids
based on indole, indazole, benzimidazole and carbazole scaffolds.
AB - Purpose: In the present study we characterized a series of synthetic cannabinoids
containing various heterocyclic scaffolds that had been identified as
constituents of "Spice", a preparation sold on the illicit drug market. All
compounds were further investigated as potential ligands of the orphan receptors
GPR18 and GPR55 that interact with some cannabinoids. Methods: The compounds were
studied in radioligand binding assays to determine their affinity for human
cannabinoid CB1 and CB2 receptors expressed in CHO cells, and in cAMP
accumulation assays to study their functionality. Results: Structure-activity
relationships were analyzed. The most potent CB1 receptor agonist of the present
series MDMB-FUBINACA (12) (Ki = 98.5 pM) was docked into the human CB1 receptor
structure, and a plausible binding mode was identified showing high similarity
with that of the co-crystallized THC derivatives. MDMB-CHMCZCA (41) displayed a
unique profile acting as a full agonist at the CB1 receptor subtype, but blocking
the CB2 receptor completely. Only a few weakly potent antagonists of GPR18 and
GPR55 were identified, and thus all compounds showed high CB receptor
selectivity, mostly interacting with both subtypes, CB1 and CB2. Conclusions:
These results will be useful to assess the compounds' toxicological risks and to
guide legislation. Further studies on 41 are warranted.
PMID- 29963208
TI - Application of the QuEChERS procedure for analysis of Delta9-tetrahydrocannabinol
and its metabolites in authentic whole blood samples by GC-MS/MS.
AB - Purpose: Analysis of drugs and their metabolites in biofluids usually demands the
application of sample preparation methods that allow for full isolation of
analyzed substances from the matrix. The purpose of this study was to develop a
method using the QuEChERS procedure for analysis of Delta9-tetrahydrocannabinol
(THC), 11-hydroxy-Delta9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy
Delta9-tetrahydrocannabinol (11-COOH-THC). Methods: THC, 11-OH-THC and 11-COOH
THC were quantified in whole blood samples using QuEChERS extraction and gas
chromatography-tandem mass spectrometry. Results: The described method is
characterized by good linearity, very low detection limits and satisfactory inter
and intraday precisions for THC, 11-OH-THC and 11-COOH-THC. The applicability of
the procedure was confirmed using authentic whole blood samples collected from 30
persons suspected of driving under the influence of drugs. Conclusions: The
application of QuEChERS extraction described herein is a simple and convenient
method for the routine analysis of THC, 11-OH-THC and 11-COOH-THC in whole blood
samples from living and deceased humans. To our knowledge, this paper is the
first academic report describing the QuEChERS extraction of THC and its
metabolites from whole blood specimens.
PMID- 29963209
TI - In vitro metabolism of synthetic cannabinoid AM1220 by human liver microsomes and
Cunninghamella elegans using liquid chromatography coupled with high resolution
mass spectrometry.
AB - Purpose: Identifying intake of synthetic cannabinoids generally requires the
metabolism data of the drugs so that appropriate metabolite markers can be
targeted in urine testing. However, the continuous appearance of new cannabinoids
during the last decade has made it difficult to keep up with all the compounds
including {1-[(1-methylpiperidin-2-yl)methyl]-1H-indol-3-yl}(naphthalen-1
yl)methanone (AM1220). In this study, metabolism of AM1220 was investigated with
human liver microsomes and the fungus Cunninghamella elegans. Methods: Metabolic
stability of AM1220 was analysed by liquid chromatography-tandem mass
spectrometry in multiple reaction monitoring mode after 1 uM incubation in human
liver microsomes for 30 min. Tentative structure elucidation of metabolites was
performed on both human liver microsome and fungal incubation samples using
liquid chromatography-high-resolution mass spectrometry. Results: Half-life of
AM1220 was estimated to be 3.7 min, indicating a high clearance drug. Nine
metabolites were detected after incubating human liver microsomes while seven
were found after incubating Cunninghamella elegans, leading to 11 metabolites in
total (five metabolites were common to both systems). Demethylation, dihydrodiol
formation, combination of the two, hydroxylation and dihydroxylation were the
observed biotransformations. Conclusions: Three most abundant metabolites in both
human liver microsomes and Cunninghamella elegans were desmethyl, dihydrodiol and
hydroxy metabolites, despite different isomers of dihydrodiol and hydroxy
metabolites in each model. These abundant metabolites can potentially be useful
markers in urinalysis for AM1220 intake.
PMID- 29963210
TI - Use of hepatocytes isolated from a liver-humanized mouse for studies on the
metabolism of drugs: application to the metabolism of fentanyl and
acetylfentanyl.
AB - Purpose: The usefulness of hepatocytes isolated from a liver-humanized mouse (PXB
cells) as a model in vitro system for the prediction of the in vivo metabolism of
new drugs of abuse was evaluated. Methods: For the drug metabolism study,
fentanyl, a powerful synthetic opioid, and acetylfentanyl, an N-acetyl analog of
fentanyl, were selected as model drugs. PXB-cells were cultured with the drug for
24-48 h and then the media were collected and analyzed by liquid
chromatography/mass spectrometry after deproteinization with acetonitrile.
Results: The main metabolite formed from fentanyl by PXB-cells was the
desphenethylated metabolite (nor-fentanyl), and the other major metabolites
formed were 4'-hydroxy-fentanyl, beta-hydroxy-fentanyl and (omega-1)-hydroxy
fentanyl. omega-Hydroxy-fentanyl and 4'-hydroxy-3'-methoxy-fentanyl were the
minor metabolites. Similar results were obtained for acetylfentanyl. The
metabolite profile of fentanyl in PXB-cells was consistent with the in vivo
metabolite profile of fentanyl reported previously. Most of the 4'-hydroxy- and
4'-hydroxy-3'-methoxy-metabolites of fentanyl and acetylfentanyl were conjugated
in PXB-cells, indicating that PXB-cells had high conjugation enzyme activities.
From experiments using human liver microsomes and anti-CYP antibodies, it was
revealed that CYP3A4 was involved in the production of nor-fentanyl, beta-hydroxy
fentanyl and (omega-1)-hydroxy-fentanyl, while CYP2D6 was partially involved in
the production of 4'-hydroxy-fentanyl. Conclusions: Our results indicated that
PXB-cells have high activities of phase I and phase II drug-metabolizing-enzymes,
can be stably supplied, and are easy to use; thus, PXB-cells are highly useful
for the prediction of the in vivo metabolism of drugs of abuse.
PMID- 29963211
TI - Blood concentrations of a new psychoactive substance 4-chloromethcathinone (4
CMC) determined in 15 forensic cases.
AB - Purpose: The 4-chloromethcathinone (4-CMC) is a synthetic derivative of cathinone
and belongs to new psychoactive substances. Neither data on the effects of 4-CMC
on the human body, nor on nontoxic, toxic and lethal concentrations in biological
materials have been published in the literature. This paper describes the results
of an analysis of the blood concentrations of 4-CMC determined in 15 forensic
cases related to nonfatal intoxication including driving under the influence, and
fatalities including overdoses, suicide and traffic accidents. Methods: A new
method for the quantification of 4-CMC using gas chromatography-mass spectrometry
(GC-MS) was developed. The symptoms of 4-CMC use were also studied based on an
analysis of the documents prepared during the collection of samples or at
autopsies. Results: The limits of detection and quantification of the method for
blood samples were 0.3 and 1 ng/mL, respectively. The calibration curve was
linear in the studied concentration range (1-500 ng/mL) with the correlation
coefficient at 0.9979. The extraction recoveries varied in the range of 94.3
98.8%. The accuracy and precision were acceptable. The determined concentrations
in nonfatal cases ranged from 1.3 to 75.3 ng/mL, and in fatalities from 56.2 to
1870 ng/mL. Conclusions: Our study can assist in the recognition of the possible
effects caused by 4-CMC and can be helpful during the preparation of forensic
toxicological opinions for courts of law. The validation parameters indicate the
sensitivity and accuracy of the method. This is the first work presenting a
validated method for the determination of 4-CMC in blood samples by GC-MS.
PMID- 29963212
TI - Metabolism of alpha-PHP and alpha-PHPP in humans and the effects of alkyl chain
lengths on the metabolism of alpha-pyrrolidinophenone-type designer drugs.
AB - Purpose: This study aims to investigate the urinary metabolites of two common
alpha-pyrrolidinophenones (PPs), alpha-pyrrolidinohexiophenone (alpha-PHP) and
alpha-pyrrolidinoheptanophenone (alpha-PHPP). This report also aims to discuss
the effects of alkyl chain lengths on the metabolism of PPs. Methods: Urinary
metabolites of alpha-PHP and alpha-PHPP have been investigated by analyzing urine
samples from their users (n = 13 each) by liquid chromatography-high-resolution
tandem mass spectrometry using reference standards of the metabolites synthesized
in our laboratory. Results and conclusions: For both drugs, metabolites via
reduction of the keto moiety (1-OH metabolites) and via oxidation of the
pyrrolidine ring (2"-oxo metabolites) were identified, and those via oxidation of
the terminal (omega) or penultimate (omega-1) positions of the alkyl chain were
tentatively identified. Quantitative analysis indicated oxidation of the
pyrrolidine ring to be the major metabolic pathway for alpha-PHP (side chain R:
hexyl), but omega or omega-1 oxidation was the major metabolic pathway for alpha
PHPP (R: heptyl). Comparison of their metabolic profiles with those of analogs
with a longer or shorter side chain (studied previously for R: butyl, pentyl, and
octyl) revealed that the alkyl chain length strongly influences the metabolic
pathway. In addition, to the best of our knowledge, this is the first report
describing the quantification of metabolites of alpha-PHP and alpha-PHPP in
authentic urine specimens collected from the users using their reference
standards synthesized.
PMID- 29963213
TI - Fatal case of poisoning with a new cathinone derivative: alpha
propylaminopentiophenone (N-PP).
AB - Purpose: Similar to synthetic cannabinoids, synthetic cathinone derivatives are
the most popular compounds among novel psychoactive substances. Along with a
growing number of new cathinones, the number of consumers wishing to enrich their
experience with these compounds is also growing, and the same can be said about
the growing numbers of poisonings. The reason for overdosing is a lack of
consumer awareness regarding composition of the product, with which they
experiment, and even more, regarding concentration of psychoactive substances
contained in the taken product. In this paper, we report a case of the purposeful
intake of a high dose of powder containing a novel cathinone derivative, alpha
propylaminopentiophenone, which resulted in the deadly poisoning of a woman.
Methods: Aiming to identify this psychoactive substance causing the fatality, the
postmortem specimens collected from the autopsy was analyzed by means of high
performance liquid chromatography coupled with mass spectrometry, and the
analysis of a powder material found with the victim was additionally analyzed by
means of gas chromatography with mass spectrometric detection. Results: In the
course of analysis performed on the specimens originating from autopsy (blood,
eyeball fluid, liver, kidney and brain), high concentrations of alpha
propylaminopentiophenone were established, which was responsible for the death of
a young woman. The same psychoactive compound was also identified in the powder
material. Conclusions: To the best of the authors' knowledge, this is the first
case reported in the literature on fatal poisoning with alpha
propyloaminopentiophenone.
PMID- 29963214
TI - Parent Engagement in Online Mindfulness Exercises Within a Parent Training
Program for Post-Deployed Military Families.
AB - Mindfulness has drawn increased attention in prevention programs targeting
parents. Commonly, mindfulness-based programs are provided to reduce parental
stress and improve child outcomes. Less often, researchers incorporate a
mindfulness-informed approach, integrating a low dose of mindfulness exercises
into an existing evidence-based parent training model. Little is known about
participant engagement with mindfulness exercises in such programs. This non
experimental study focuses on families who are at risk for impaired parenting due
to the unique stressor of a parent's deployment to war. The goal is to examine
military parents' online engagement in mindfulness exercises and associations
between engagement and dispositional mindfulness within a web-enhanced parent
training program. Online tracking records and self-reported data were obtained
from 370 military parents (207 families) who were assigned to the program; at 6
month follow-up, 68.6% of these parents were retained (at least one parent
reported from 75.4% of families). Results showed that nearly half (44.6%) of the
parents engaged with the exercises. Participants who attended face-to-face group
sessions (i.e., attendees) engaged throughout the intervention period whereas
participants who never attended group sessions (i.e., non-attendees) mostly
engaged during the first month in the program. Attendees and mothers engaged more
than non-attendees and fathers. While engaged parents self-reported increased
dispositional mindfulness at 6-month follow-up compared to baseline, only
mothers' engagement accounted for a significant proportion of the variance (3%)
in dispositional mindfulness at 6-month follow-up, after controlling for
covariates. Implications for incorporating online mindfulness exercises into
parent training are discussed in the context of programming for military
families.
PMID- 29963215
TI - Time from Semiosis: E-series Time for Living Systems.
AB - We develop a semiotic scheme of time, in which time precipitates from the
repeated succession of punctuating the progressive tense by the perfect tense.
The underlying principle is communication among local participants. Time can thus
be seen as a meaning-making, semiotic system in which different time codes are
delineated, each having its own grammar and timekeeping. The four time codes
discussed are the following: the subjective time having tense, the objective time
without tense, the static time without timekeeping, and the inter-subjective time
of the E-series. Living organisms adopt a time code called the E-series, which
emerges through the local synchronization among organisms or parts of organisms.
The inter-subjective time is a new theoretical dimension resulting from the time
aligning activities of interacting agents. Such synchronization in natural
settings consists of incessant mutual corrections and adjustments to one's own
punctuation, which is then constantly updated. Unlike the third-person observer
keeping the objective time while sitting outside a clock, the second-person
negotiators participate in forming the E-series time by punctuating and updating
the interface through which different tenses meet at the moment of "now."
Although physics allows physicists to be the only interpreters, the semiotic
perspective upends the physical perspective by letting local participants be
involved in the interpretation of their mutual negotiations to precipitate that
which is called time.
PMID- 29963216
TI - Molecular Reorientation during the Initial Growth of Perfluoropentacene on
Ag(110).
AB - Perfluoropentacene (PFP) is an organic material that has been widely studied over
the last years and has already found applications in organic electronics.
However, fundamental physical questions, such as the structural formation and the
preferential orientation of the molecules during deposition on metal surfaces,
are still not fully understood. In this work, we report on a unique in-plane
molecular reorientation during the completion of the first monolayer of PFP on
the Ag(110) surface. To characterize the molecular alignment, we have monitored
the deposition process in real time using polarization-dependent differential
reflectance spectroscopy and reflectance anisotropy spectroscopy. Abrupt changes
in the optical signals reveal an intricate sequence of reorientation transitions
of the PFP molecules upon monolayer completion and during the formation of the
second monolayer, eventually leading to a full alignment of the long molecular
axis along the [001] direction of the substrate and an enhanced structural
ordering. Scanning tunneling microscopy and low-energy electron diffraction
confirm the observed molecular reorientation upon monolayer compression and
provide further details on the structural and orientational ordering of the PFP
monolayer before and after compression.
PMID- 29963217
TI - The Nonmarket Benefits of Education and Ability.
AB - This paper analyzes the non-market benefits of education and ability. Using a
dynamic model of educational choice we estimate returns to education that account
for selection bias and sorting on gains. We investigate a range of non-market
outcomes including incarceration, mental health, voter participation, trust, and
participation in welfare. We find distinct patterns of returns that depend on the
levels of schooling and ability. Unlike the monetary benefits of education, the
benefits to education for many non-market outcomes are greater for low-ability
persons. College graduation decreases welfare use, lowers depression, and raises
self-esteem more for less-able individuals.
PMID- 29963218
TI - Co-occurrence of Witnessed Parental Violence and Child Physical Abuse from a
National Sample of Adolescents.
AB - This study examined the relations between witnessed parental violence (PV) and
child physical abuse (CPA) over a one-year period among a nationally
representative sample of 2,514 adolescents, ages 12-18. History of witnessed PV
(Wave 1) prospectively predicted new experiences (controlling for abuse history)
and first experiences of CPA reported at Wave 2. Conversely, history of CPA
predicted new experiences of PV, but not first experiences. For adolescents who
reported witnessed PV and CPA, witnessed PV preceded CPA in 70% of cases. Most
common configuration was single-perpetrator of violence. Additional perpetrator
and sequencing configurations are reported. Study findings addressed several
limitations in the literature by including use of adolescent report, longitudinal
design, inclusion of perpetrator identity, and a nationally representative
sample.
PMID- 29963219
TI - A propensity score approach to estimating child restraint effectiveness in
preventing mortality.
AB - Confounding between the child's restraint use and driver behavior can bias
restraint effectiveness estimates away from the null if survivable crashes are
more common in certain restraint types. Analyzing only fatal crashes may
introduce selection bias toward the null because any protective effects of a
restraint type will underrepresent children in that restraint. A marginal
structural-model-type estimator suggests a 17% reduction in fatality risk for
children aged 2 through 6 in child restraint systems relative to seat belts. This
reduction is estimated at 22% when severe misuse of the restraint is excluded.
PMID- 29963221
TI - Improving the simulation of convective dust storms in regional-to-global models.
AB - Convective dust storms have significant impacts on atmospheric conditions and air
quality and are a major source of dust uplift in summertime. However, regional-to
global models generally do not accurately simulate these storms, a limitation
that can be attributed to (1) using a single mean value for wind speed per grid
box, i.e., not accounting for subgrid wind variability and (2) using convective
parametrizations that poorly simulate cold pool outflows. This study aims to
improve the simulation of convective dust storms by tackling these two issues.
Specifically, we incorporate a probability distribution function for surface wind
in each grid box to account for subgrid wind variability due to dry and moist
convection. Furthermore, we use lightning assimilation to increase the accuracy
of the convective parameterization and simulated cold pool outflows. This updated
model framework is used to simulate a massive convective dust storm that hit
Phoenix, AZ, on 6 July 2011. The results show that lightning assimilation
provides a more realistic simulation of precipitation features, including timing
and location, and the resulting cold pool outflows that generated the dust storm.
When those results are combined with a dust model that accounts for subgrid wind
variability, the prediction of dust uplift and concentrations are considerably
improved compared to the default model results. This modeling framework could
potentially improve the simulation of convective dust storms in global models,
regional climate simulations, and retrospective air quality studies.
PMID- 29963220
TI - Myocardial Assessment with Cardiac CT: Ischemic Heart Disease and Beyond.
AB - Purpose of Review: The aim of this review is to highlight recent advancements,
current trends, and the expanding role for cardiac CT (CCT) in the evaluation of
ischemic heart disease, nonischemic cardiomyopathies, and some specific
congenital myocardial disease states. Recent Findings: CCT is a highly versatile
imaging modality for the assessment of numerous cardiovascular disease states.
Coronary CT angiography (CCTA) is now a well-established first-line imaging
modality for the exclusion of significant coronary artery disease (CAD); however,
CCTA has modest positive predictive value and specificity for diagnosing
obstructive CAD in addition to limited capability to evaluate myocardial tissue
characteristics. Summary: CTP, when combined with CCTA, presents the potential
for full functional and anatomic assessment with a single modality. CCT is a
useful adjunct in select patients to both TTE and CMR in the evaluation of
ventricular volumes and systolic function. Newer applications, such as dynamic
CTP and DECT, are promising diagnostic tools offering the possibility of more
quantitative assessment of ischemia. The superior spatial resolution and
volumetric acquisition of CCT has an important role in the diagnosis of other
nonischemic causes of cardiomyopathies.
PMID- 29963222
TI - Probabilistic graphical models relate immune status with response to neoadjuvant
chemotherapy in breast cancer.
AB - Breast cancer is the most frequent tumor in women and its incidence is
increasing. Neoadjuvant chemotherapy has become standard of care as a complement
to surgery in locally advanced or poor-prognosis early stage disease. The
achievement of a complete response to neoadjuvant chemotherapy correlates with
prognosis but it is not possible to predict who will obtain an excellent
response. The molecular analysis of the tumor offers a unique opportunity to
unveil predictive factors. In this work, gene expression profiling in 279 tumor
samples from patients receiving neoadjuvant chemotherapy was performed and
probabilistic graphical models were used. This approach enables addressing
biological and clinical questions from a Systems Biology perspective, allowing to
deal with large gene expression data and their interactions. Tumors presenting
complete response to neoadjuvant chemotherapy had a higher activity of immune
related functions compared to resistant tumors. Similarly, samples from complete
responders presented higher expression of lymphocyte cell lineage markers, immune
activating and immune-suppressive markers, which may correlate with tumor
infiltration by lymphocytes (TILs). These results suggest that the patient's
immune system plays a key role in tumor response to neoadjuvant treatment.
However, future studies with larger cohorts are necessary to validate these
hypotheses.
PMID- 29963223
TI - Malignant transformation of uterine leiomyoma to myxoid leiomyosarcoma after
morcellation associated with ALK rearrangement and loss of 14q.
AB - A 50 year old woman underwent laparoscopic supracervical hysterectomy because of
symptomatic fibroids. Histologic examination of samples obtained after
morcellation revealed typical uterine leiomyomas in all samples investigated. 28
and 47 months later, respectively, the patient presented with peritoneal
spreading of nodules that were surgically removed and histologically classified
as leiomyosarcoma. In 3/4 of samples obtained after morcellation copy number/SNP
array hybridization showed complex genomic alterations widely identical to the
pattern characterizing the sarcoma. Therefore, we conclude that the
leiomyosarcoma had unambiguously developed from one of the leiomyomas as a result
of secondary genetic alterations i.e. a rearrangement of ALK and a del(14q). The
case is challenging the current risk estimates for spreading of unexpected
malignant uterine tumors due to power morcellation and highlights the relevance
of certain genetic alterations for rare malignant transformation of uterine
benign smooth muscle tumors.
PMID- 29963224
TI - Comprehensive identification of long noncoding RNAs in colorectal cancer.
AB - Colorectal cancer (CRC) is one of the most common cancers in humans and a leading
cause of cancer-related deaths worldwide. As in the case of other cancers, CRC
heterogeneity leads to a wide range of clinical outcomes and complicates therapy.
Over the years, multiple factors have emerged as markers of CRC heterogeneity,
improving tumor classification and selection of therapeutic strategies.
Understanding the molecular mechanisms underlying this heterogeneity remains a
major challenge. A considerable research effort is therefore devoted to
identifying additional features of colorectal tumors, in order to better
understand CRC etiology and to multiply therapeutic avenues. Recently, long
noncoding RNAs (lncRNAs) have emerged as important players in physiological and
pathological processes, including CRC. Here we looked for lncRNAs that might
contribute to the various colorectal tumor phenotypes. We thus monitored the
expression of 4898 lncRNA genes across 566 CRC samples and identified 282 lncRNAs
reflecting CRC heterogeneity. We then inferred potential functions of these
lncRNAs. Our results highlight lncRNAs that may participate in the major
processes altered in distinct CRC cases, such as WNT/beta-catenin and TGF-beta
signaling, immunity, the epithelial-to-mesenchymal transition (EMT), and
angiogenesis. For several candidates, we provide experimental evidence supporting
our functional predictions that they may be involved in the cell cycle or the
EMT. Overall, our work identifies lncRNAs associated with key CRC characteristics
and provides insights into their respective functions. Our findings constitute a
further step towards understanding the contribution of lncRNAs to CRC
heterogeneity. They may open new therapeutic opportunities.
PMID- 29963225
TI - Inhibition of GSK3alpha/beta impairs the progression of HNSCC.
AB - Background: Head and neck squamous cell cancer (HNSCC) is one of the most common
tumors worldwide and there is an enormous need for innovative therapy approaches.
Several recent studies suggest tumor entity specific roles of glycogen synthase
kinase 3 (GSK3) in different human cancers, acting as tumor suppressor or as
tumor promoter. Here we describe the role of GSK3 with respect to different
parameters within HNSCC progression. Methods: Base line expression and activity
profiles of p-GSK3alpha/beta (Ser21/9) and p-GSK3alpha/beta (Tyr279/216) were
analyzed by immunohistochemistry and western blotting. Four different permanent
HNSCC cell lines were exposed to the potent GSK3alpha/beta inhibitor SB 216763.
Cell viability was controlled via the MTT test. Cell migration was quantified
with the Real Time Cell Analyzer (RCTA) xCELLigence. Regulation of the epithelial
mesenchymal transition (EMT) was measured with the Human Epithelial to
Mesenchymal Transition (EMT) RT2 ProfilerTM PCR Array and scratch assays. Taqman
probes were used to detect the specific gene expression profiles of inflammatory
cytokines Interleukin IL1beta, IL6, IL8, IL10, TNFalpha and IFNbeta. Results:
Exposure of permanent HNSCC cell lines to the specific GSK3alpha/beta inhibitor
SB 216763 leads to significant growth inhibition, inhibition of migration and
decreased levels of active GSK3alpha/beta in a dose dependent manner.Exposure of
HNSCC lines to SB 216763 also resulted in a markable shift of EMT markers and
functional EMT dysregulation. Functionally GSK3 differentially mediates the
expression of TLR4- and TLR3-induced inflammatory cytokines in HNSCC, whereas no
effect of SB 216763 on the NFkB activity was noticed. Conclusion: GSK3alpha/beta
plays a crucial role in a variety of regulatory networks for HNSCC cancer
progression as it drives proliferation or migration and thus GSK3 could serve as
an interesting target for clinical drug development.
PMID- 29963226
TI - The small molecule STF-62247 induces apoptotic and autophagic cell death in
leukemic cells.
AB - Adult T cell leukemia/lymphoma (ATL) is an aggressive malignant T cell disease
caused by human T cell leukemia virus-I (HTLV-1). Treatment outcomes for
aggressive subtypes of ATL remain poor, with little improvement in overall
survival since HTLV-1 was discovered. Therefore, new therapeutic strategies for
ATL are required. STF-62247 induces autophagy and selectively kills renal cell
carcinoma without apoptotic cell death. Here, we demonstrate that STF-62247
reduced cell viability and resulted in autophagosome accumulation and autophagy
in leukemic cell lines (S1T, MT-2, and Jurkat). Interestingly, STF-62247 induced
apoptosis in HTLV-1-infected cell lines (S1T and MT-2), as indicated by DNA
fragmentation and caspase activation, but not in non-HTLV-1-infected Jurkat
cells; a caspase inhibitor did not prevent this caspase-associated cell death.
STF-62247 also increased nuclear endonuclease G levels. Furthermore, STF-62247
reduced cell viability and increased the number of apoptotic cells in peripheral
blood mononuclear cells collected from patients with acute ATL, which has a poor
prognosis. Therefore, STF-62247 may have novel therapeutic potential for ATL.
This is the first evidence to demonstrate the cell growth-inhibitory effect of an
autophagy inducer by caspase-dependent apoptosis and caspase-independent cell
death via autophagy and endonuclease G in leukemic cells.
PMID- 29963227
TI - Identification of differentially expressed miRNAs and miRNA-targeted genes in
bladder cancer.
AB - Background: Differentially expressed genes and their post-transcriptional
regulator-microRNAs (miRNAs), are potential keys to pioneering cancer diagnosis
and treatment. The aim of this study was to investigate how the miRNA-mRNA
interactions might affect the tumorigenesis of bladder cancer (BC) and to
identify specific miRNA and mRNA genetic markers in the two BC types: non-muscle
invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).
Results: We identified 227 genes that interacted with 54 miRNAs in NMIBC, and 14
genes that interacted with 10 miRNAs in MIBC. Based on this data, we found
extracellular matrix-related genes are highly enriched in NMIBC while genes
related to core nuclear division are highly enriched in MIBC. Furthermore, using
a transcriptional regulatory element database, we found indirect regulatory
transcription factors (TFs) for enriched genes could regulate tumorigenesis with
or without miRNAs. Materials and methods: Tissue samples from 234 patients
histologically diagnosed with BC and 83 individuals without BC were analyzed
using microarray and next-generation sequencing technology, and we used different
cut-offs to identify differentially expressed mRNAs and miRNAs in NMIBC and MIBC.
The selected mRNAs and miRNAs were paired using validated target datasets and
according to inverse expression relationships. MiRNA interacted genes were
compared with the TF-regulating genes in BC. Meanwhile, pathway enrichment
analysis was performed to identify the functions of selected miRNAs and genes.
Conclusions: Identification of differential gene expression in specific tumor
types could facilitate development of cancer diagnosis and aid in the early
detection of BC.
PMID- 29963230
TI - PKM2 under hypoxic environment causes resistance to mTOR inhibitor in human
castration resistant prostate cancer.
AB - The aim of this study was to explore the efficacy of mTOR inhibitor for
castration-resistant prostate cancer (CRPC) under hypoxia. Although under
normoxia C4-2AT6, it is a CRPC cell line, expressed elevated pAkt, pS6 and
Pyruvate kinase M2 (PKM2) accompanied by elevated HIF-1a expression, 5% hypoxic
condition further induced expression of these proteins. These results indicate
hypoxic environment elevated PI3K/Akt/mTOR pathway in aggressive prostate cancer.
However, C4-2AT6 cells treated with mTOR inhibitor under hypoxia less decreased
compared to cells treated with the same dose drugs under normoxia. Western blot
analysis showed mTOR inhibitor: RAD001 not only inhibited pS6, but also increased
the expression of PKM2 in a dose and time dependent manner. Pyruvate kinase acts
on glycolysis. PKM2, which is frequently express in tumor cells, is one isoform
of pyruvate kinase. PKM2 is reported to act as a transcription factor. In the
present study overexpression of PKM2 in C4-2AT6 induced resistance to RAD001
under normoxia. To evaluate the therapeutic effect of targeting PKM2, we
inhibited PKM2 in C4-2AT6 under hypoxia using si-PKM2. The number of C4-2AT6
under chronic hypoxia exposed to siPKM2 significantly decreased compared to
intact C4-2AT6 under chronic hypoxia. Furthermore, si-PKM2 improved resistance to
mTOR inhibitor in C4-2AT6. When examined using clinical samples, high PKM2
expression was correlated with a high Gleason score and poor PSA free survival.
These results suggested that up-regulation of PKM2 is one possibility of
resistance to mTOR inhibitor in CRPC. And it is possible that PKM2 is a useful
therapeutic target of CRPC.
PMID- 29963229
TI - New susceptibility loci for cutaneous melanoma risk and progression revealed
using a porcine model.
AB - Despite major advances, it is estimated that a large part of melanoma
predisposing genes remains to be discovered. Animal models of spontaneous
diseases are valuable tools and experimental crosses can be used to identify and
fine-map new susceptibility loci associated with melanoma. We performed a Genome
Wide Association Study (GWAS) of melanoma occurrence and progression (clinical
ulceration and presence of metastasis) in a porcine model of spontaneous
melanoma, the MeLiM pig. Five loci on chromosomes 2, 5, 7, 8 and 16 showed genome
wide significant associations (p < 5 * 10-6) with either one of these phenotypes.
Suggestive associations (p < 5 * 10-5) were also found at 16 additional loci.
Moreover, comparison of the porcine results to those reported by human melanoma
GWAS indicated shared association signals notably at CDKAL1 and TERT loci but
also nearby CCND1, FTO, PLA2G6 and TMEM38B-RAD23B loci. Extensive search of the
literature revealed a potential key role of genes at the identified porcine loci
in tumor invasion (DST, PLEKHA5, CBY1, LIMK2 and ETV5) and immune response
modulation (ETV5, HERC3 and DICER1) of the progression phenotypes. These
biological processes are consistent with the clinico-pathological features of
MeLiM tumors and can open new routes for future melanoma research in humans.
PMID- 29963228
TI - Enhanced proteasomal activity is essential for long term survival and recurrence
of innately radiation resistant residual glioblastoma cells.
AB - Therapy resistance and recurrence in Glioblastoma is due to the presence of
residual radiation resistant cells. However, because of their inaccessibility
from patient biopsies, the molecular mechanisms driving their survival remain
unexplored. Residual Radiation Resistant (RR) and Relapse (R) cells were captured
using cellular radiation resistant model generated from patient derived primary
cultures and cell lines. iTRAQ based quantitative proteomics was performed to
identify pathways unique to RR cells followed by in vitro and in vivo experiments
showing their role in radio-resistance. 2720 proteins were identified across
Parent (P), RR and R population with 824 and 874 differential proteins in RR and
R cells. Unsupervised clustering showed proteasome pathway as the most
significantly deregulated pathway in RR cells. Concordantly, the RR cells
displayed enhanced expression and activity of proteasome subunits, which
triggered NFkB signalling. Pharmacological inhibition of proteasome activity led
to impeded NFkB transcriptional activity, radio-sensitization of RR cells in
vitro, and significantly reduced capacity to form orthotopic tumours in vivo. We
demonstrate that combination of proteasome inhibitor with radio-therapy abolish
the inaccessible residual resistant cells thereby preventing GBM recurrence.
Furthermore, we identified first proteomic signature of RR cells that can be
exploited for GBM therapeutics.
PMID- 29963231
TI - FOXP3 and miR-155 cooperate to control the invasive potential of human breast
cancer cells by down regulating ZEB2 independently of ZEB1.
AB - Control of oncogenes, including ZEB1 and ZEB2, is a major checkpoint for
preventing cancer, and loss of this control contributes to many cancers,
including breast cancer. Thus tumour suppressors, such as FOXP3, which is mutated
or lost in many cancer tissues, play an important role in maintaining normal
tissue homeostasis. Here we show for the first time that ZEB2 is selectively down
regulated by FOXP3 and also by the FOXP3 induced microRNA, miR-155.
Interestingly, neither FOXP3 nor miR-155 directly altered the expression of ZEB1.
In breast cancer cells repression of ZEB2, independently of ZEB1, resulted in
reduced expression of a mesenchymal marker, Vimentin and reduced invasion.
However, there was no de-repression of E-cadherin and migration was enhanced.
Small interfering RNAs targeting ZEB2 suggest that this was a direct effect of
ZEB2 and not FOXP3/miR-155. In normal human mammary epithelial cells, depletion
of endogenous FOXP3 resulted in de-repression of ZEB2, accompanied by upregulated
expression of vimentin, increased E-cadherin expression and cell morphological
changes. We suggest that FOXP3 may help maintain normal breast epithelial
characteristics through regulation of ZEB2, and loss of FOXP3 in breast cancer
cells results in deregulation of ZEB2.
PMID- 29963232
TI - Real-time methylation-specific PCR for the evaluation of methylation status of
MGMT gene in glioblastoma.
AB - The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene
is a strong predictor for the efficacy of temozolomide chemotherapy and survival
periods. However, the correlation between the extent of methylation and the
difference in survival times has not been fully clarified. Simple and
quantitative evaluations of the methylation status in the promotor region of the
MGMT gene are expected to be worldwide standardized diagnostics. We applied real
time semi-quantitative methylation-specific polymerase chain reaction (SQ-MSP) of
the MGMT gene promoter region to 84 glioblastoma patients. The SQ-MSP result
showed that the DeltaCt value, which represents the difference between uCt and
mCt (uCt value - mCt value), is inversely correlated with overall survival. With
adequate cutoff setting, this assay showed that those patients suffering from a
tumor with low DeltaCt (methylated) survived significantly longer than those
having tumors with high DeltaCt (un-methylated). The most significant difference
was observed when the cutoff was set at a DeltaCt of 2. Using this cutoff point,
the result of MGMT immunohistochemical analysis was also significantly correlated
with the methylation status examined with real-time SQ-MSP. These results
collectively show that MGMT promoter methylation status actually affects
patients' survival and protein expression depending on its methylation level, and
the extent of methylated CpGs would be better assessed with real-time SQ-MSP than
with the standard gel-based MSP. This method is cost- and labor-saving compared
with pyrosequencing, and significantly contributes to the accurate and objective
prediction of patient survival.
PMID- 29963234
TI - The difference in the survival rate of patients with metastatic renal cell
carcinoma in the intermediate-risk group of the Memorial Sloan Kettering Cancer
Center criteria.
AB - Objectives: To investigate the necessity of stratifying patients in the
intermediate-risk group of the Memorial Sloan Kettering Cancer Center (MSKCC)
criteria in a real-world population of patients with metastatic renal cell
carcinoma. Patients and Methods: We retrospectively analyzed 234 consecutively
treated patients who had received molecular targeted drugs. We examined the
difference between progression-free survival and overall survival among patients
in the intermediate-risk group of MSKCC criteria. We divided the intermediate
group into two subgroups as follows: patients positive for only one risk factor
(Int-1) and those positive for two risk factors (Int-2) including performance
status, serum hemoglobin level, time from diagnosis to treatment, and corrected
calcium and lactate dehydrogenase levels. Next, we evaluated the association
between the number of metastatic organs, the presence of pancreatic metastasis,
Int-1 or Int-2 grouping, and overall survival. Results: The median overall
survival was 41.2 months. The median overall survival of the favorable-,
intermediate-, and poor-risk groups of the MSKCC criteria were 91.0, 33.6, and
15.2 months, respectively. Patient characteristics were similar between the Int-1
and Int-2 groups. Increased positivity for risk factors of MSKCC classification
between the two groups was for performance status and serum hemoglobin level.
Progression-free survival and overall survival of the Int-1 group were
significantly higher than those of the Int-2 group. In Cox proportional stepwise
multivariate analysis, the Int-1 and Int-2 classification was an independent risk
factor for overall survival. Conclusion: Patients in the intermediate-risk group
had different prognoses depending on the number of positive risk factors.
PMID- 29963233
TI - ERalpha-mediated cell cycle progression is an important requisite for CDK4/6
inhibitor response in HR+ breast cancer.
AB - While ER has multiple biological effects, ER-cyclin D1-CDK4/6-RB is a critical
pathway for the action of estrogen on the cell cycle, especially for breast
cancers that rely on estrogen for growth. The latest and most efficient CDK4/6
inhibitors target the phosphorylation of retinoblastoma (RB) tumor suppressor
gene; thus, altering levels of many cell cycle molecules. Estrogen receptor
(ER)+/HER2- breast cancers have shown great progression free survival when CDK4/6
inhibitors are combined with endocrine therapies. Here we report the mechanism of
antiestrogen (fulvestrant) combination with CDK4/6 inhibitors is due to synergism
in the suppression of ER-mediated cell cycle progression. Furthermore, we
performed single cell analysis of cells from an estrogen dependent/hormone
receptor-positive patient derived xenograft (PDX) tumor model treated with
palbociclib. These single cells expressed various levels of ER and RB which are
involved in cell cycle regulation; and the response to palbociclib treatment
relies not only on the ER-cyclin D1-CDK4/6-RB pathway but it is also dependent on
elevated levels of ER and/or RB. Our preclinical studies show that palbociclib
response is dependent on cells with ER, which is directly involved in cell cycle
progression in hormone receptor positive (HR+) breast cancer.
PMID- 29963235
TI - Targeting the extradomain A of fibronectin allows identification of vascular
resistance to antiangiogenic therapy in experimental glioma.
AB - Introduction: Clinical application of antiangiogenic therapy lacks direct
visualization of therapy efficacy and vascular resistance. We aimed to establish
molecular imaging during treatment with sunitinib using the fibronectin
extradomain A specific small immunoprotein(SIP)-F8 in glioma. Methods:
Biodistribution analysis of F8-SIP-Alexa-555 was performed in SF126-glioma
bearing or control mice (n = 23 and 7, respectively). Intravital microscopy(IVM)
was performed on a microvascular level after 7 days (n = 5 per group) and
subsequently after 6 days of sunitinib treatment (n = 4) or without (n =
2).Additionally, near infrared fluorescence(NIRF) imaging was established with F8
SIP-Alexa-750 allowing non-invasive imaging with and without antiangiogenic
treatment in orthotopic tumors (n = 38 divided in 4 groups). MRI was used to
determine tumor size and served as a reference for NIRF imaging. Results: F8-SIP
demonstrated a time and hemodynamic dependent tumor specific accumulation. A
significantly higher vascular accumulation occurred with antiangiogenic treatment
compared to untreated tumors enabling visualization of resistant tumor vessels by
F8-SIP-mediated NIRF imaging. In orthotopic tumors, sunitinib reduced F8-SIP
Alexa-750 enrichment volume but not fluorescence intensity indicative of F8-SIP
accumulation in fewer vessels. Conclusion: F8-SIP is highly tumor specific with
time and hemodynamic dependent biodistribution. The higher vascular accumulation
to remaining vessels enables molecular imaging and targeting of therapy resistant
tumor vessels.
PMID- 29963236
TI - Activating HER3 mutations in breast cancer.
AB - Recent studies have highlighted a role of HER3 in ER and HER2-driven breast
cancers. We sought to investigate the role of patient-derived HER3 mutations in
ER+ and HER2+ breast cancer cells using ectopic expression of HER3 mutants. We
found that HER3T355I mutant is activating with increased cell proliferation in
ER+ T47D and MCF-7 breast cancer cells lacking HER2 over-expression.
Immunoblotting and receptor tyrosine kinase array results indicated that T47D and
MCF-7 cells expressing HER3T355I had increased p-HER4 and p-HER1 expression. Our
data showed that HER3T355I induced cell proliferation is via HER4/HER1-dependent
ERK1/2 and cyclinD1 mediated pathways in ER+ cells. ERalpha expression is
upregulated in ER+ cells expressing HER3T355I mutant. We noted crosstalk between
ERalpha and HER3 in T47D cells. Several HER3 mutants (F94L, G284R, D297Y, T355I,
and E1261A) acquired a gain-of-function phenotype in MCF10AHER2 cells and were
resistant to lapatinib. These mutants increased HER2-HER3 heterodimerization.
Knocking down HER3 from ovarian and colorectal cancers with endogenous HER3
mutations abrogated cancer cell proliferation. Overall, this study provides the
first systematic assessment of how mutations in HER3 affect response of ER+ and
HER2+ breast cancers to clinically relevant inhibitors and finds that HER3
mutations can be activating independent of HER2 over-expression.
PMID- 29963237
TI - Docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte-colony
stimulating factor for pretreated non-small cell lung cancer.
AB - Purpose: The aim of our study was to evaluate the efficacy and safety of
docetaxel plus ramucirumab with primary prophylactic pegylated (PEG)-granulocyte
colony stimulating factor (G-CSF) for pretreated non-small cell lung cancer
(NSCLC). Results: Sixty-one pretreated NSCLC patients underwent docetaxel plus
ramucirumab. Primary prophylactic PEG-G-CSF was performed in 52 (85%) patients
(prophylactic group). No febrile neutropenia (FN) (0%) was confirmed in 52
prophylactic group patients, whereas FN was observed in 3 (33%) of 9 non
prophylactic group patients. Among prophylactic group, median lines of prior
therapy was 2 (range, 1-9). Median cycles of docetaxel plus ramucirumab was 3
(range, 1-25) (9 and 3 cases moved to ramucirumab and docetaxel monotherapies,
respectively). Response rate and disease control rate were 30.8% and 73.1%,
respectively. Median progression-free survival was 4.5 (95% confidence interval
[CI], 3.0-6.6) months. Median overall survival was 11.4 (95% CI, 8.0-13.9)
months. Six (11.5%) patients had grade 3/4 neutropenia. Observed grade 3
(incidence >=10%) adverse event (AE) was oral mucositis (13.5%). There were no
grade 4/5 non-hematological AEs. Conclusions: Our study demonstrated the efficacy
and safety of docetaxel plus ramucirumab with PEG-G-CSF in clinical practice.
Primary prophylactic PEG-G-CSF could markedly reduce incidence of FN. Methods: We
retrospectively reviewed medical records of pretreated NSCLC cases who had
received docetaxel plus ramucirumab in our departments.
PMID- 29963238
TI - A versatile T cell-based assay to assess therapeutic antigen-specific PD-1
targeted approaches.
AB - Blockade of programmed cell death protein 1 (PD-1) immune checkpoint receptor
signaling is an established standard treatment for many types of cancer and
indications are expanding. Successful clinical trials using monoclonal antibodies
targeting PD-1 signaling have boosted preclinical research, encouraging
development of novel therapeutics. Standardized assays to evaluate their
bioactivity, however, remain restricted. The robust bioassays available all lack
antigen-specificity. Here, we developed an antigen-specific, short-term and high
throughput T cell assay with versatile readout possibilities. A genetically
modified T cell receptor (TCR)-deficient T cell line was stably transduced with
PD-1. Transfection with messenger RNA encoding a TCR of interest and subsequent
overnight stimulation with antigen-presenting cells, results in eGFP-positive and
granzyme B-producing T cells for single cell or bulk analysis. Control antigen
presenting cells induced reproducible high antigen-specific eGFP and granzyme B
expression. Upon PD-1 interaction, ligand-positive antigen-presenting immune or
tumor cells elicited significantly lower eGFP and granzyme B expression, which
could be restored by anti-PD-(L)1 blocking antibodies. This convenient cell-based
assay shows a valuable tool for translational and clinical research on antigen
specific checkpoint-targeted therapy approaches.
PMID- 29963239
TI - The rabbit as an orthologous small animal model for APOBEC3A oncogenesis.
AB - APOBEC3 are cytidine deaminases that convert cytidine to uridine residues.
APOBEC3A and APOBEC3B enzymes able to target genomic DNA are involved in
oncogenesis of a sizeable proportion of human cancers. While the APOBEC3 locus is
conserved in mammals, it encodes from 1-7 genes. APOBEC3A is conserved in most
mammals, although absent in pigs, cats and throughout Rodentia whereas APOBEC3B
is restricted to the Primate order. Here we show that the rabbit APOBEC3 locus
encodes two genes of which APOBEC3A enzyme is strictly orthologous to human
APOBEC3A. The rabbit enzyme is expressed in the nucleus and the cytoplasm, it can
deaminate cytidine, 5-methcytidine residues, nuclear DNA and induce double-strand
DNA breaks. The rabbit APOBEC3A enzyme is negatively regulated by the rabbit
TRIB3 pseudokinase protein which is guardian of genome integrity, just like its
human counterpart. This indicates that the APOBEC3A/TRIB3 pair is conserved over
approximately 100 million years. The rabbit APOBEC3A gene is widely expressed in
rabbit tissues, unlike human APOBEC3A. These data demonstrate that rabbit could
be used as a small animal model for studying APOBEC3 driven oncogenesis.
PMID- 29963240
TI - A novel oncogenic role for urokinase receptor in leukemia cells: molecular sponge
for oncosuppressor microRNAs.
AB - Urokinase receptor (uPAR) expression is up-regulated and represents a negative
prognostic marker in most cancers. We previously reported that uPAR and CXCR4 can
be regulated by common microRNAs in leukemia cells. Transcripts containing
response elements for shared microRNAs in their 3'UTR may regulate their
availability. We investigated uPAR 3'UTR capability to recruit microRNAs, thus
regulating the expression of their targets. uPAR 3'UTR transfection in KG1
leukemia cells up-regulates the expression of endogenous uPAR. Transfection of
uPAR 3'UTR, inserted downstream a reporter gene, increases uPAR expression and
simultaneously down-regulates the reporter gene expression. Transfection of uPAR
3'UTR also increases CXCR4 expression; accordingly, uPAR silencing induces down
regulation of CXCR4 expression, through a mechanism involving Dicer, the
endoribonuclease required for microRNA maturation. Transfection of uPAR 3'UTR
also increases the expression of pro-tumoral factors and modulates cell adhesion
and migration, consistently with the capability of uPAR3'UTR-recruited microRNAs
to target several and different transcripts and, thus, functions. Finally, we
found 3'UTR-containing variants of uPAR transcript in U937 leukemia cells, which
show higher levels of uPAR expression as compared to KG1 cells, in which these
variants are not detected. These results suggest that uPAR mRNA may recruit
oncosuppressor microRNAs, allowing the expression of their targets.
PMID- 29963241
TI - Survivin antagonizes chemotherapy-induced cell death of colorectal cancer cells.
AB - Irinotecan (CPT-11) and oxaliplatin (L-OHP) are among the most frequently used
drugs against colorectal tumors. Therefore, it is important to define the
molecular mechanisms that these agents modulate in colon cancer cells. Here we
demonstrate that CPT-11 stalls such cells in the G2/M phase of the cell cycle,
induces an accumulation of the tumor suppressor p53, the replicative stress/DNA
damage marker gammaH2AX, phosphorylation of the checkpoint kinases ATM and ATR,
and an ATR-dependent accumulation of the pro-survival molecule survivin. L-OHP
reduces the number of cells in S-phase, stalls cell cycle progression,
transiently triggers an accumulation of low levels of gammaH2AX and
phosphorylated checkpoint kinases, and L-OHP suppresses survivin expression at
the mRNA and protein levels. Compared to CPT-11, L-OHP is a stronger inducer of
caspases and p53-dependent apoptosis. Overexpression and RNAi against survivin
reveal that this factor critically antagonizes caspase-dependent apoptosis in
cells treated with CPT-11 and L-OHP. We additionally show that L-OHP suppresses
survivin through p53 and its downstream target p21, which stalls cell cycle
progression as a cyclin-dependent kinase inhibitor (CDKi). These data shed new
light on the regulation of survivin by two clinically significant drugs and its
biological and predictive relevance in drug-exposed cancer cells.
PMID- 29963242
TI - Feasibility of using stereotactic body radiation therapy for unresectable soft
tissue tumors of the trunk.
AB - Purpose: To evaluate the feasibility of stereotactic body radiation therapy
(SBRT) for unresectable soft tissue tumors of the trunk. Materials and Methods:
Between January 2002 and December 2008, 23 patients with 36 lesions of soft
tissue tumors, which were located in the trunk and not suitable for resection,
underwent SBRT. Among the 36 lesions, 31 were malignant and 5 were benign. The
median tumor volume was 24 cm3 (range, 2.6-213 cm3). SBRT doses ranged from 20 to
48 Gy in 1-5 fractions. Results: With a median follow-up of 73 months, the
overall survival (OS) and local control (LC) rates at 5 years were 39% and 52%,
respectively. For malignant tumors, the OS and LC rates at 5 years were 28% and
47%, respectively. For benign tumors, the OS and LC rates at 5 years were 80% and
100%, respectively. There was no acute toxicity of grade >=3. One case of grade 3
late skin toxicity was reported 10 months after SBRT. Conclusion: SBRT may be an
effective and safe treatment modality for the local control of unresectable soft
tissue tumors of the trunk including tumors of a benign nature.
PMID- 29963243
TI - Interferon-stimulated gene 20 kDa protein serum levels and clinical outcome of
hepatitis B virus-related liver diseases.
AB - Interferon-stimulated gene 20 kDa protein (ISG20) with 3' to 5' exonuclease
activity mainly targeting single-stranded RNA plays an important role in immune
responses against various infectious pathogens, including hepatitis viruses.
ISG20 levels were measured by ELISA assays in sera of 339 hepatitis B-virus (HBV)
infected patients and 71 healthy individuals and were correlated with clinical
and laboratory parameters. ISG20 mRNA was quantified by qRT-PCR in 30 pairs of
hepatocellular carcinoma (HCC) tumour and adjacent non-tumour liver tissues.
ISG20 levels were significantly elevated in HBV patients compared to healthy
controls (P<0.0001). In the patient group, varying ISG20 levels were associated
with different forms of HBV-related liver diseases. ISG20 levels were higher in
patients with HCC compared to those without HCC (P<0.0001), and increased
according to the stages of HCC (P<0.0001). ISG20 mRNA expression was up-regulated
in tumour tissues compared to the expression in adjacent non-tumour tissues
(P=0.017). Importantly, ISG20 levels were strongly correlated with the levels of
AST, ALT, total and direct bilirubin among HCC patients (Pearson's r = 0.43,
0.35, 0.34, 0.3; P<0.0001, respectively). Although differences between liver
cirrhosis (LC) and non-LC patients were not observed, ISG20 levels were elevated
according to the progression of cirrhosis in patients with LC plus HCC (P=0.005).
In conclusions, ISG20 levels are induced by HBV infection and significantly
associated with progression and clinical outcome of HBV-related liver diseases,
especially in patients with HCC. ISG20 might be a potential indicator for liver
injury and the clinical outcome in HBV-related HCC.
PMID- 29963244
TI - Dietary patterns and primary liver cancer in Chinese adults: a case-control
study.
AB - Introduction: Healthy dietary patterns may prevent many chronic diseases, and is
emphasized by 2015 US dietary guideline, but it remains unclear which dietary
patterns may be benefit to prevention of primary liver cancer (PLC). Materials
and Methods: We recruited 782 PLC cases and 1:1 age- and sex-matched controls in
Guangzhou, China. Habitual dietary intake was assessed by face-to-face interview
using a 79-item food frequency questionnaire, and used to explore dietary
patterns by factor analysis. Results: Three dietary patterns were identified: 1)
an urban prudent dietary pattern (UPDP) characterized by high in dairy products,
eggs, mushrooms, nuts and soy foods, but low in refined grains; 2) a traditional
Cantonese dietary pattern (TCDP) consisting of a high intake of fruit and
vegetables, fish, Cantonese soup, and Chinese herb tea; and 3) a high meat and
preserved food pattern (MPFP). Multivariable analyses showed favorable
associations for the first two dietary patterns, but unfavorable association for
the last one (all p-trend < 0.01). Odds ratios (95% CI) of PLC for the highest
(vs. lowest) quartile of pattern scores of the three patterns were 0.25 (0.18
0.35), 0.61 (0.46-0.82), and 1.98 (1.46-2.69), respectively. Conclusions: Our
findings suggest that the UPDP and TCDP were associated with lower, whereas the
MPFP with higher, risk of PLC.
PMID- 29963245
TI - Efficacy of azacitidine is independent of molecular and clinical characteristics
an analysis of 128 patients with myelodysplastic syndromes or acute myeloid
leukemia and a review of the literature.
AB - Azacitidine is the first drug to demonstrate a survival benefit for patients with
MDS. However, only half of patients respond and almost all patients eventually
relapse. Limited and conflicting data are available on predictive factors
influencing response. We analyzed 128 patients from two institutions with MDS or
AML treated with azacitidine to identify prognostic indicators. Genetic mutations
in ASXL1, RUNX1, DNMT3A, IDH1, IDH2, TET2, TP53, NRAS, KRAS, FLT3, KMT2A-PTD,
EZH2, SF3B1, and SRSF2 were assessed by next-generation sequencing. With a median
follow up of 5.6 years median survival was 1.3 years with a response rate of 49%.
The only variable with significant influence on response was del(20q). All 6
patients responded (p = 0.012) but survival was not improved. No other clinical,
cytogenetic or molecular marker for response or survival was identified.
Interestingly, patients from poor-risk groups as high-risk cytogenetics (55%), t
MDS/AML (54%), TP53 mutated (48%) or relapsed after chemotherapy (60%) showed a
high response rate. Factors associated with shorter survival were low platelets,
AML vs. MDS, therapy-related disease, TP53 and KMT2A-PTD. In multivariate
analysis anemia, platelets, FLT3-ITD, and therapy-related disease remained in the
model. Poor-risk factors such as del(7q)/-7, complex karyotype, ASXL1, RUNX1,
EZH2, and TP53 did not show an independent impact. Thus, no clear biomarker for
response and survival can be identified. Although a number of publications on
predictive markers for response to AZA exist, results are inconsistent and
improved response rates did not translate to improved survival. Here, we provide
a comprehensive overview comparing the studies published to date.
PMID- 29963247
TI - Correction: Dietary cholesterol intake and stroke risk: a meta-analysis.
AB - [This corrects the article DOI: 10.18632/oncotarget.23933.].
PMID- 29963248
TI - Correction: Endonuclease G promotes mitochondrial genome cleavage and
replication.
AB - [This corrects the article DOI: 10.18632/oncotarget.24822.].
PMID- 29963249
TI - Does cancer strive to minimize the cost of gene expression?
PMID- 29963246
TI - Breast cancer recurrence after reconstruction: know thine enemy.
AB - Breast reconstruction proceeding cancer treatment carries risk, regardless of the
type of surgery. From fat grafting, to flap placement, to implants, there is no
guarantee that reconstruction will not stimulate breast cancer recurrence.
Research in this field is clearly divided into two parts: scientific
interventional studies and clinical retrospective evidence. The reconstructive
procedure offers hypoxia, a wound microenvironment, bacterial load, adipose
derived stem cells; agents shown experimentally to cause increased cancer cell
activity. This is compelling scientific evidence which serves to bring
uncertainty and fear to the reconstructive procedure. In the absence of clinical
evidence, this laboratory literature landscape is now informing surgical choices.
Curiously, clinical studies have not shown a clear link between breast cancer
recurrence and reconstructive surgery. Where does that leave us? This review aims
to analyze the science and the surgery, thereby understanding the oncological
fear which accompanies breast cancer reconstruction.
PMID- 29963250
TI - Next generation sequencing identifies miRNA-based biomarker panel for lupus
nephritis.
AB - The symptomatology of lupus nephritis (LN) consists of foamy urine and lower leg
edema, as well as such systemic manifestations as oral ulcers,
arthralgia/arthritis, and lymphadenopathy. However, these symptoms may appear
mild and non-specific. If these symptoms are unrecognized, thus delaying
treatment, approximately 10% of LN patients will develop permanent kidney damage
and end-stage kidney disease. Therefore, the purpose of this study is to identify
a surrogate biomarker for the early detection of LN. In this study, we first
adopted next generation sequencing (NGS) in order to screen differential
expression levels of microRNA between SLE patients with and without LN. The
results of both the NGS and the literature review confirmed the potential of 15
microRNAs through real-time qPCR. We further considered clinical laboratory data
for additional analysis. In total, 41 microRNAs demonstrated significant
differences through NGS screening. We then verified eight microRNAs from NGS and
seven microRNAs from the literature review using the real-time qPCR method in
peripheral mononuclear cells. Ultimately, mir-125a-5p, miR-146a-5p, and mir-221
3p were found to be statistically significant not only in the screening study but
also in the real-time qPCR verification studies. miR-146a-5p was observed to have
a significant correlation with clinical biochemistry markers, as well as to be a
surrogate biomarker for the early detection of lupus nephritis. This study is the
first to show that the intracellular biomarker miR-146a-5p may serve as a useful
specific biomarker for the detection of lupus nephritis among lupus patients in
the future, regardless of serum albumin levels and spot urine protein/creatinine
ratio.
PMID- 29963251
TI - MiR-205 as predictive biomarker and adjuvant therapeutic tool in combination with
trastuzumab.
AB - Trastuzumab is the standard treatment for HER2+ breast cancer (BC) patients, and
even though it significantly improved their clinical outcome, 50% of them do not
benefit from this drug and disease recurs, underlining the need of reliable
predictive biomarkers and new therapeutic strategies. Strikingly, despite all the
molecular analyses performed to identify the escape mechanisms behind this
resistance, it still represents a question point. MiRNAs have been correlated
with occurrence and progression of human cancer, and their potential as clinical
tools has emerged in the last years. We previously reported that oncosuppressive
miR-205 targets HER3, thus increasing the responsiveness to TKIs lapatinib and
gefitinib in preclinical models. Here we demonstrate that HER3 inhibition by miR
205 ectopic expression or siRNA-mediated silencing improves the responsiveness to
Trastuzumab in vitro in HER2+ BC cell lines, and that this effect is exerted
through impairment of AKT-mediated pathway. Moreover, evaluating a series of 52
HER2+ BC patients treated with adjuvant Trastuzumab, we observed that higher miR
205 expression is significantly associated with better outcome (disease-free
survival). In summary, our data indicate that miR-205 could predict Trastuzumab
efficacy and that its modulation might be useful as adjuvant treatment to improve
the response to the drug.
PMID- 29963252
TI - T790M mutant copy number quantified via ddPCR predicts outcome after osimertinib
treatment in lung cancer.
AB - Osimertinib prolongs progression-free survival (PFS) in patients with metastatic,
epidermal growth factor receptor (EGFR) T790M-mutated, non-small cell lung cancer
(NSCLC) after failure of EGFR tyrosine kinase inhibitor (TKI) therapy. We
investigated the utility of T790M mutant copy number quantification in a plasma
cell-free DNA (cfDNA) assay for predicting clinical outcomes of osimertinib
treatment. We retrospectively examined 161 patients who underwent plasma EGFR
testing using a digital droplet polymerase chain reaction (ddPCR) technique after
EGFR-TKI failure. Of the 74 (46%) patients with detectable T790M mutations in
plasma, 55 received osimertinib treatment. Patients who achieved partial response
had a higher plasma mutant copy levels than those with progressive disease.
Patients who achieved stable disease also tended to have higher plasma mutant
copy levels than those with progressive disease. High mutant copy number (>= 105
per mL of plasma) was associated with shorter PFS (median: 5.5 months vs. not
reached) and overall survival (median: 9.1 months vs. NR). Quantitative
measurements of T790M mutant copy number in plasma cfDNA by ddPCR thus predicted
treatment response and survival outcomes after osimertinib in NSCLC patients
resistant to EGFR TKI.
PMID- 29963253
TI - The proteoglycan-like domain of carbonic anhydrase IX mediates non-catalytic
facilitation of lactate transport in cancer cells.
AB - Highly glycolytic tumor cells release vast amounts of lactate and protons via
monocarboxylate transporters (MCTs), which exacerbate extracellular acidification
and support the formation of a hostile environment. Transport activity of MCTs
can be facilitated by non-catalytic interaction with carbonic anhydrase IX
(CAIX), the expression of which has been shown to be upregulated under hypoxia.
We have now studied the mechanisms that enable CAIX-mediated facilitation of
proton-coupled lactate transport in breast cancer cells and Xenopus oocytes. Our
results indicate that the proteoglycan like (PG) domain of CAIX could function as
'proton antenna' to facilitate MCT transport activity. Truncation of the PG
domain and application of a PG-binding antibody significantly reduced proton
coupled lactate transport in MCT-expressing oocytes and hypoxic breast cancer
cells, respectively. Furthermore, application of the PG-binding antibody reduced
proliferation and migration of hypoxic cancer cells, suggesting that facilitation
of proton-coupled lactate flux by the CAIX PG domain contributes to cancer cell
survival under hypoxic conditions.
PMID- 29963254
TI - Two birds, one stone: hesperetin alleviates chemotherapy-induced diarrhea and
potentiates tumor inhibition.
AB - Chemotherapy-induced diarrhea (CID), with clinical high incidence, adversely
affects the efficacy of cancer treatment and patients' quality of life. Our study
demonstrates that the citrus flavonoid hesperetin (Hst) has a superior potential
as a new agent to prevent and alleviate CID. In the animal model for irinotecan
(CPT-11) induced CID, Hst could selectively inhibit intestinal carboxylesterase
(CES2) and thus reduce the local conversion of CPT-11 to cytotoxic SN-38 which
causes intestinal toxicity. Oral administration of Hst manifested an excellent
anti-diarrhea efficacy, prohibiting 80% of severe and 100% of mild diarrhea in
the CPT-11 administered tumor-bearing mice. In addition, a significant
attenuation of intestinal inflammation contributed to the anti-diarrhea effect of
Hst. Moreover, Hst was found to work synergistically with CPT-11 in tumor
inhibition by suppressing the tumor's STAT3 activity and recruiting tumoricidal
macrophages into the tumor microenvironment. The anti-intestinal inflammation and
anti-STAT3 properties of Hst would contribute its broad benefits to the
management of diarrhea caused by other chemo or targeted agents, and more
importantly, enhance and reinforce the anti-tumor effects of these agents, to
improve patient outcomes.
PMID- 29963255
TI - Cancer cell death induced by ferritins and the peculiar role of their labile iron
pool.
AB - Cellular uptake of human H-ferritin loaded with 50 or 350 iron ions results in
significant cytotoxicity on HeLa cells at submicromolar concentrations.
Conversely, Horse Spleen Ferritin, that can be considered a model of L-cages, as
it contains only about 10% of H subunits, even when loaded with 1000 iron ions,
is toxic only at >1 order of magnitude higher protein concentrations. We propose
here that the different cytotoxicity of the two ferritin cages originates from
the presence in H-ferritin of a pool of non-biomineralized iron ions bound at the
ferroxidase catalytic sites of H-ferritin subunits. This iron pool is readily
released during the endosomal-mediated H-ferritin internalization.
PMID- 29963256
TI - Nucleoporin 153 regulates estrogen-dependent nuclear translocation of endothelial
nitric oxide synthase and estrogen receptor beta in prostate cancer.
AB - Nucleoporin 153 (Nup153), key regulator of nuclear import/export, has been
recently associated to oncogenic properties in pancreatic and breast tumour cells
modulating either cell motility and migration or gene expression by chromatin
association. In the present work, we have characterized the role of Nup153 in a
cellular model of prostate cancer (PCa). The analysis of several immortalized
cell lines derived from freshly explants of prostate cancer specimens showed that
Nup153 protein was higher and present in multimeric complexes with eNOS and
ERbeta as compared to normal/hyperplastic prostate epithelial cells. This
phenomenon was enhanced in the presence of 17beta-estradiol (E2, 10-7M). Further
experiments revealed that eNOS and ERbeta were present in a DNA binding complexes
associated with Nup153 promoter as demonstrated by ChIPs. Notably, after Nup153
depletion (siNup153), a reduction of migration capacity and colony formation in
primary tumor-derived and metastatic PCa cells was observed. In addition, eNOS
and ERbeta nuclear localization was lost upon siNup 153 regardless of E2
treatment, suggesting that Nup153 is a key regulator of prostate cancer cell
function and of the nuclear translocation of these proteins in response to
hormone stimulus. Taken altogether our findings indicate that in PCa cells: i.
the expression and function of Nup153 is modulated by estrogen signaling; ii.
Nup153 contributes to cell migration and proliferation; iii. Nup153 regulates the
nuclear translocation of eNOS and ERbeta by forming a multimeric complex. Our
findings unveil Nup153 as a novel component of the estrogen-dependent multimeric
complex, thus representing a potential therapeutic candidate in prostate cancer.
PMID- 29963257
TI - Probiotic DSF counteracts chemotherapy induced neuropathic pain.
AB - PROBLEM STATEMENT: Chemotherapy-induced peripheral neuropathy (CIPN) is a
widespread and potentially disabling side effect of various anticancer drugs. In
spite of the intensive research focused on obtaining therapies capable to treat
or prevent CIPN, the medical demand remains very high. Microtubule-stabilizing
agents, among which taxanes, are effective chemotherapeutic agents for the
therapy of several oncologic diseases. The inflammatory process activated by
chemotherapeutic agents has been interpreted as a potential trigger of the
nociceptive process in CIPN. The chemotherapy-driven release of proinflammatory
and chemokines has been recognized as one of the principal mechanisms controlling
the establishment of CIPN. Several reports have indicated that probiotics are
capable to regulate the balance of anti-inflammatory and pro-inflammatory
cytokines. Accordingly, it has been suggested that some probiotic formulations,
may have an effective role in the management of inflammatory pain symptoms.
Experimental approaches used: we tested the hypothesis that paclitaxel-induced
neuropathic pain can be counteracted by the probiotic DSF by using an in vitro
model of sensitive neuron, the F11 cells. On this model, the biomolecular
pathways involved in chemotherapy induced peripheral neuropathy depending on
inflammatory cytokines were investigated by Real-time PCR, Western blotting and
confocal microscopy. General conclusions: the results obtained, i.e. the increase
of acetylated tubulin, the increase of the active forms of proteins involved in
the establishment of neuropathic pain, point towards the use of this probiotic
formulation as a possible adjuvant agent for counteracting CINP symptoms.
PMID- 29963258
TI - Intracranial hemangioblastoma - A SEER-based analysis 2004-2013.
AB - Introduction: Intracranial hemangioblastoma (HB) is a rare pathology. Limited
data exist regarding its epidemiology. Methods: With the SEER-18 registry
database, information from all patients diagnosed with intracranial HB from 2004
to 2013 were extracted, including age, gender, race, marital status, presence of
surgery, extent of surgery, receipt of radiation, tumor size, tumor location, and
follow-up data. Age-adjusted incidence rates and overall survival (OS). Cox
proportional hazards model was employed for both univariate and multivariate
analyses. Results: A total of 1307 cases were identified. The overall incidence
of intracranial hemangioblastoma is 0.153 per 100,000 person-years [95%
confidence interval (CI)=0.145-0.162]. Through univariate analysis, age < 40
[hazard ratio (HR)=0.277, p<0.001], no radiation [HR=0.56, p=0.047], and presence
of surgery [HR=0.576, p=0.012] are significant positive prognostic factors.
Caucasian race [HR=1.42, p=0.071] and female gender [HR=0.744, p=0.087] exhibit
noticeable trends towards positive prognosis. Through multivariate analysis,
younger age [HR=1.053, p < 0.01], race [HR=1.916, p<0.01], and presence of
surgery [HR=0.463, p<0.01 were significant independent prognostic factors.
Conclusion: Clinical factors such as younger age, Caucasian race, and presence of
surgery are significant independent factors for overall survival in patients with
HBs. Though analysis regarding extent of surgery did not produce a meaningful
relationship, this may be related to surgical bias / expertise. Moreover, no
validation for radiation therapy was identified, but this may be related to short
follow up intervals and the variable growth patterns of HBs.
PMID- 29963259
TI - In silico-designed mutations increase variable new-antigen receptor single-domain
antibodies for VEGF165 neutralization.
AB - The stability, binding, and tissue penetration of variable new-antigen receptor
(VNAR) single-domain antibodies have been tested as part of an investigation into
their ability to serve as novel therapeutics. V13 is a VNAR that recognizes
vascular endothelial growth factor 165 (VEGF165). In the present study V13 was
used as a parental molecule into which we introduced mutations designed in
silico. Two of the designed VNAR mutants were expressed, and their ability to
recognize VEGF165 was assessed in vitro and in vivo. One mutation (Pro98Tyr) was
designed to increase VEGF165 recognition, while the other (Arg97Ala) was designed
to inhibit VEGF165 binding. Compared to parental V13, the Pro98Tyr mutant showed
enhanced VEGF165 recognition and neutralization, as indicated by inhibition of
angiogenesis and tumor growth. This molecule thus appears to have therapeutic
potential for neutralizing VEGF165 in cancer treatment.
PMID- 29963260
TI - Activity of roniciclib in medullary thyroid cancer.
AB - Altered cyclin-dependent kinase activity is observed in many human malignancies.
Cyclin-dependent kinases that promote cell cycle progression may be promising
targets in the treatment of cancer. The therapeutic effects of roniciclib, a
cyclin-dependent kinase inhibitor for medullary thyroid cancer were investigated
in the present study. Roniciclib inhibited medullary thyroid cancer cell
proliferation in a dose-dependent manner. Roniciclib induced caspase-3 activity
and contributed to apoptosis. Cell cycle progression was arrested in the G2
phase. In vivo, roniciclib treatment retarded the growth of tumors of medullary
thyroid cancer xenografts. In addition, roniciclib in combination with sorafenib
was more effective than either single treatment in a xenograft model. No
morbidity was observed in animals treated with single roniciclib therapy and
combination treatment of roniciclib and sorafenib. These data provide a rationale
for clinical assessment of using roniciclib in the treatment of patients with
medullary thyroid cancer.
PMID- 29963261
TI - Antiproliferative effects of two gold(I)-N-heterocyclic carbene complexes in
A2780 human ovarian cancer cells: a comparative proteomic study.
AB - Au(NHC) and Au(NHC)2, i.e. a monocarbene gold(I) complex and the corresponding
bis(carbene) complex, are two structurally related compounds, endowed with
cytotoxic properties against several cancer cell lines. Herein, we explore the
molecular and cellular mechanisms at the basis of their cytotoxicity in A2780
human ovarian cancer cells. Through a comparative proteomic analysis, we
demonstrated that the number of modulated proteins is far larger in Au(NHC)2
treated than in Au(NHC)-treated A2780 cells. Both gold compounds mainly affected
proteins belonging to the following functional classes: protein synthesis,
metabolism, cytoskeleton and stress response and chaperones. Particularly,
Au(NHC)2 gave rise to an evident upregulation of several glycolytic enzymes.
Moreover, only Au(NHC)2 triggered a net impairment of respiration and a metabolic
shift towards glycolysis, suggesting that mitochondria are relevant cellular
targets. We also found that both carbenes, similarly to the gold(I) compound
auranofin, caused a strong inhibition of the seleno-enzyme thioredoxin reductase
(TrxR). In conclusion, we highlighted that coordination of two carbene ligands to
the same gold(I) center greatly enhances the antiproliferative effects of the
resulting compound in comparison to the monocarbene derivative. Moreover, TrxR
inhibition and metabolic impairment seem to play a major role in the Au(NHC)2
cytotoxicity. Overall, these antiproliferative effects were also confirmed on
other two human ovarian cancer cell lines (i.e. SKOV3 and IGROV1).
PMID- 29963262
TI - The combination of everolimus and zoledronic acid increase the efficacy of
gemcitabine in a mouse model of pancreatic adenocarcinoma.
AB - Background: Gemcitabine is a standard treatment for pancreatic adenocarcinoma.
Many mechanisms are involved in gemcitabine resistance, such as reduced
expression of the human equilibrative nucleoside transporter 1 (hENT1) membrane
transporter, deoxycytidine kinase deficiency, and changes in the signal
transmission of mitogen-activity protein kinase (MAPK) and the phosphoinositide 3
kinase (PI3K) pathways. Aim: To evaluate the anti-tumor efficiency of blocking
signaling pathways using combined action of gemcitabine, everolimus and
zoledronic acid versus gemcitabine alone in a mouse subcutaneous xenograft.
Methods: Implantations of two human pancreatic adenocarcinoma cells lines (PANC1,
K-ras mutated and gemcitabine-resistant; and BxPc3, wild-type K-ras and
gemcitabine-sensitive) were performed on male athymic nude mice. The mice
received different treatments: gemcitabine, gemcitabine plus everolimus,
everolimus, gemcitabine plus zoledronic acid, everolimus plus zoledronic acid, or
gemcitabine plus everolimus and zoledronic acid, for 28 days. We measured the
tumor volume and researched the expression of the biomarkers involved in the
signaling pathways or in gemcitabine resistance. Results: In wild-type K-ras
tumors, the combinations of gemcitabine plus everolimus; zoledronic acid plus
everolimus; and gemcitabine plus zoledronic acid and everolimus slowed tumor
growth, probably due to caspase-3 overexpression and reduced Annexin II
expression. In mutated K-ras tumors, gemcitabine plus everolimus and zoledronic
acid, and the combination of zoledronic acid and everolimus, decreased tumor
volume as compared to gemcitabine alone, inhibiting the ERK feedback loop induced
by everolimus. Conclusion: The combination of zoledronic acid and everolimus has
an antitumor effect and could increase gemcitabine efficacy.
PMID- 29963263
TI - Prognostic stratification of adult primary glioblastoma multiforme patients based
on their tumor gene amplification profiles.
AB - Several classification systems have been proposed to address genomic
heterogeneity of glioblastoma multiforme, but they either showed limited
prognostic value and/or are difficult to implement in routine diagnostics. Here
we propose a prognostic stratification model for these primary tumors based on
tumor gene amplification profiles, that might be easily implemented in routine
diagnostics, and potentially improve the patients management. Gene amplification
profiles were prospectively evaluated in 80 primary glioblastoma multiforme
tumors using single-nucleotide polymorphism arrays and the results obtained
validated in publicly available data from 267/347 cases. Gene amplification was
detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was
the most frequently amplified chromosomal region - either alone (18%) or in
combination with amplification of DNA sequences in other chromosomal regions (10%
of cases). Other frequently amplified DNA sequences included regions in
chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification
profiles, glioblastomas were subdivided into: i) tumors with no gene
amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with
or without amplification of other chromosomal regions) (38%); and iii)
glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA
sequences in chromosomal regions other than chromosome 7p. From the prognostic
point of view, these amplification profiles showed a significant impact on
overall survival of glioblastoma multiforme patients (p>0.001). Based on these
gene amplification profiles, a risk-stratification scoring system was built for
prognostic stratification of glioblastoma which might be easily implemented in
routine diagnostics, and potentially contribute to improved patient management.
PMID- 29963265
TI - Cancer stem cells from peritumoral tissue of glioblastoma multiforme: the
possible missing link between tumor development and progression.
AB - In glioblastoma multiforme (GBM), cancer stem cells (CSCs) are thought to be
responsible for gliomagenesis, resistance to treatment and recurrence.
Unfortunately, the prognosis for GBM remains poor and recurrence frequently
occurs in the peritumoral tissue within 2 cm from the tumor edge. In this area, a
population of CSCs has been demonstrated which may recapitulate the tumor after
surgical resection. In the present study, we aimed to characterize CSCs derived
from both peritumoral tissue (PCSCs) and GBM (GCSCs) in order to deepen their
significance in GBM development and progression. The stemness of PCSC/GCSC pairs
obtained from four human GBM surgical specimens was investigated by comparing the
expression of specific stem cell markers such as Nestin, Musashi-1 and SOX2. In
addition, the growth rate, the ultrastructural features and the expression of
other molecules such as c-Met, pMet and MAP kinases, involved in cell
migration/invasion, maintenance of tumor stemness and/or resistance to treatments
were evaluated. Since it has been recently demonstrated the involvement of the
long non-coding RNAs (lncRNAs) in the progression of gliomas, the expression of
H19 lncRNA, as well as of one of its two mature products miR-675-5p was evaluated
in neurospheres. Our results show significant differences between GCSCs and PCSCs
in terms of proliferation, ultrastructural peculiarities and, at a lower extent,
stemness profile. These differences might be important in view of their potential
role as a therapeutic target.
PMID- 29963264
TI - MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic
neuroepithelial tumours and astrocytomas.
AB - Glioneuronal tumours, including gangliogliomas and dysembryoplastic
neuroepithelial tumours, represent the most common low-grade epilepsy-associated
brain tumours and are a well-recognized cause of intractable focal epilepsy in
children and young adults. Classification is predominantly based on histological
features, which is difficult due to the broad histological spectrum of these
tumours. The aim of the present study was to find molecular markers that can be
used to identify entities within the histopathology spectrum of glioneuronal
tumours. The focus of this study was on microRNAs (miRNAs). miRNAs are important
post-transcriptional regulators of gene expression and are involved in the
pathogenesis of different neurological diseases and oncogenesis. Using a miRNA
array, miR-519d and miR-4758 were found to be upregulated in gangliogliomas
(n=26) compared to control cortex (n=17), peritumoural tissue (n=7),
dysembryoplastic neuroepithelial tumours (n=9) and astrocytomas (grade I-IV;
subependymal giant cell astrocytomas, n=10; pilocytic astrocytoma, n=15; diffuse
astrocytoma grade II, n=10; grade III, n=14 and glioblastoma n=15). Furthermore,
the PI3K/AKT3/P21 pathway, which is predicated to be targeted by miR-519d and miR
4758, was deregulated in gangliogliomas. Functionally, overexpression of miR-519d
in an astrocytic cell line resulted in a downregulation of CDKN1A (P21) and an
increase in cell proliferation, whereas co-transfection with miR-4758
counteracted this effect. These results suggest that miR-519d and miR-4758 might
work in concert as regulators of the cell cycle in low grade gliomas.
Furthermore, these miRNAs could be used to distinguish gangliogliomas from
dysembryoplastic neuroepithelial tumours and other low and high grade gliomas and
may lead to more targeted therapy.
PMID- 29963266
TI - High serum vascular endothelial growth factor C predicts better relapse-free
survival in early clinically node-negative breast cancer.
AB - A recent meta-analysis indicated that higher tumoral expression of vascular
endothelial growth factor C (VEGF-C) was related to poorer relapse-free and
overall survival in breast cancer patients. However, a retrospective study found
that higher circulating VEGF-C levels were associated with better survival in
breast cancer patients. In 2009, we initiated a prospective study to determine
the utility of preoperative serum VEGF-C levels for predicting the risk of
sentinel lymph node involvement in early breast cancer and to assess serum VEGF-C
levels as a prognostic factor for relapse-free and overall survival. We analyzed
serum samples from 174 patients with early breast cancer who underwent sentinel
lymph node biopsies. VEGF-C levels were determined using an ELISA. Serum VEGF-C
levels were normally distributed, with a median value of 6561.5 pg/mL, and did
not correlate with any other clinical or pathological variables. During a median
follow-up period of 58 months, the five-year relapse-free survival rate was
higher in patients with VEGF-C levels above the median than in patients with
lower levels (95.3% vs. 85.9%, p < 0.04). No association was found between VEGF-C
levels and overall survival. Our study demonstrates that the prognosis was better
for early breast cancer patients with high serum VEGF-C levels.
PMID- 29963267
TI - Small non-coding RNA landscape is modified by GPAT2 silencing in MDA-MB-231
cells.
AB - Glycerol-3-phosphate acyltransferase-2 is a member of "cancer-testis gene"
family. Initially linked to lipid metabolism, this gene has been recently found
involved also in PIWI-interacting RNAs biogenesis in germline stem cells. To
investigate its role in piRNA metabolism in cancer, the gene was silenced in MDA
MB-231 breast cancer cells and small RNA sequencing was applied. PIWI-interacting
RNAs and tRNA-derived fragments expression profiles showed changes following
GPAT2 silencing. Interestingly, a marked shift in length distribution for both
small RNAs was detected in GPAT2-silenced cells. Most downregulated PIWI
interacting RNAs are single copy in the genome, intragenic, hosted in snoRNAs and
previously found to be upregulated in cancer cells. Putative targets of these
PIWI-interacting RNAs are linked to lipid metabolism. Downregulated tRNA derived
fragments derived from, so-called 'differentiation tRNAs', whereas upregulated
ones derived from proliferation-linked tRNAs. miRNA amounts decrease after
Glycerol-3-phosphate acyltransferase-2 silencing and functional enrichment
analysis of deregulated miRNA putative targets point to mitochondrial biogenesis,
IGF1R signaling and oxidative metabolism of lipids and lipoproteins. In addition,
miRNAs known to be overexpressed in breast cancer tumors with poor prognosis
where found downregulated in GPAT2-silenced cells. In conclusion, GPAT2 silencing
quantitatively and qualitatively affects the population of PIWI-interacting RNAs,
tRNA derived fragments and miRNAs which, in combination, result in a more
differentiated cancer cell phenotype.
PMID- 29963268
TI - Combined alkylation and histone deacetylase inhibition with EDO-S101 has
significant therapeutic activity against brain tumors in preclinical models.
AB - There is a clear unmet need for novel therapeutic agents for management of
primary and secondary brain tumors. Novel therapeutic agents with excellent
central nervous system (CNS) penetration and therapeutic activity are urgently
needed. EDO-S101 is a novel alkylating and histone deacetylase inhibiting agent
created by covalent fusion of bendamustine and vorinostat. We used murine models
to perform CNS pharmacokinetic analysis and preclinical therapeutic evaluation of
EDO-S101 for CNS lymphoma, metastatic triple-negative breast cancer of the brain,
and glioblastoma multiforme. EDO-S101 has excellent CNS penetration of 13.8% and
16.5% by intravenous infusion and bolus administration respectively. It shows
promising therapeutic activity against CNS lymphoma, metastatic triple-negative
breast cancer of the brain, and glioblastoma multiforme with significant
prolongation of survival compared to no-treatment controls. Therapeutic activity
was higher with IV infusion compared to IV bolus. It should be evaluated further
for therapeutic use in brain tumors.
PMID- 29963269
TI - Mining of potential microRNAs with clinical correlation - regulation of syndecan
1 expression by miR-122-5p altered mobility of breast cancer cells and possible
correlation with liver injury.
AB - MicroRNAs are small noncoding RNAs acting as novel biomarkers of various diseases
and potential regulators of protein expression and functions. Syndecan-1 is the
heparan sulfate proteoglycan associated with malignancy of various cancers,
including breast cancer. In this study, we proposed a experimental workflow to
investigate potential microRNAs that regulate SDC1 expression and affect breast
cancer cell mobility. MicroRNA candidates were selected from available Gene
Expression Omnibus datasets on breast malignancy. Further in silico duplex
hybridization and multiplex PCR approach were used to screen potential microRNAs.
Analysis showed increased syndecan-1 expression but decreased miR-122-5p level
upon breast malignancy. Western blot and in vitro luciferase assay confirmed the
targeting of 3'-untranslated region of syndecan-1 and suppression of syndecan-1
expression by miR-122-5p. The suppression of syndecan-1 expression by miR-122-5p
or shRNAs against syndecan-1 increased breast cancer cell mobility; while
overexpression of syndecan-1 inhibited cell mobility. In further, miR-122-5p was
enriched in liver cell-derived exosomes that was able to suppress syndecan-1
expression and increase cell mobility in breast cancer cells. In conclusion, our
results suggested the downregulation of SDC1 by miR-122-5p or liver-cell-derived
exosomes would enhance breast cancer cell mobility. Metastasis or mobility of
breast cancer cells might be affected by circulating miR-122-5p and not directly
correlated with progression of breast cancer.
PMID- 29963270
TI - Refusal to take a sick leave as an estimate of the phenomenon of presenteeism in
Poland.
AB - Introduction: Absenteeism and presenteeism are two main phenomena related to
health problems and professional activity. Presenteeism is the involvement in a
professional activity despite being ill. The purpose of the current study is to
estimate the prevalence of presenteeism in Poland on the basis of medical records
and to explore associations between presenteeism and patients' age, gender and
type of medical problem. Another purpose is to provide estimates of the length of
sick leave if it was accepted. Results: The amount of patients who refused to
take a sick leave was 27.4%. There was a minor relationship between the refusals
and gender (slightly higher in men) as well as strong effects of the age of
patients (periods of sick leave were longer in older patients) and ICD-10
diagnosis (largely in acute diseases of the upper respiratory tract). The
estimated number of days spent on sick leave in the group of patients that
refused to take it, assuming that they made a different decision and complied to
it, was in the range between 5 and 10 days. Discussion: The prevalence of
presenteeism in Poland is relatively high. Since the largest proportion of
refusals took place in the case of potentially contagious diseases, the negative
impact on productivity may be even higher. Even though the relationship between
presenteeism and wages remains unclear, the remarkable increase of wages in
Poland within the last 20 years may explain the propensity to work despite being
ill. Further research needs to consider the simultaneous use of medical records
and self-measured productivity loss. Materials and Methods: The current study is
based on data from medical records concerning 550,360 patients aged 19-64.
Associations between refusals to take a sick leave and patients' age, gender, as
well as diagnosis in terms of ICD-10 (International Statistical Classification of
Diseases and Related Health Problems), were tested. Linear regression analysis on
the data acquired from the patients who accepted to take a sick leave were
further used to estimate the possible length of sick leave in the group of
patients that refused to take it.
PMID- 29963271
TI - Risk factors of ineffective drainage in uncovered self-expandable metal stenting
for unresectable malignant hilar biliary strictures.
AB - Aim: In this study, we assessed the factors contributing to ineffective drainage
in the initial transpapillary uncovered self-expandable metal stent (USEMS)
placements in patients with unresectable malignant hilar biliary strictures
(UMHBSs) (Bismuth type II or higher). Methods: This was a retrospective, single
center study. A total of 97 patients with UMHBSs who underwent technically
successful initial USEMS placements using endoscopic retrograde
cholangiopancreatography (ERCP) were classified into the effective drainage group
(n = 73) or the ineffective drainage group (n = 24). We then compared group
characteristics, clinical outcomes, and drained liver volumes. Drained liver
volume was measured by using computed tomography volumetry. The definition of
effective biliary drainage was a 50% decrease in the serum total bilirubin level
or normalization of the level within 14 days of stent placement. Results:
Univariate analysis showed that ineffective drainage was associated with the pre
ERCP serum total bilirubin level (P = 0.0075), pre-ERCP serum albumin level (P =
0.042), comorbid liver cirrhosis (P = 0.010), drained liver volume (P = 0.0010),
and single stenting (P = 0.022). Multivariate analysis identified comorbid liver
cirrhosis (adjusted odds ratio [OR], 5.79; 95% confidence interval [CI], 1.30
25.85; P = 0.022) and drained liver volume < 50% (adjusted OR, 5.50; 95% CI, 1.50
20.25; P = 0.010) as independent risk factors of ineffective drainage.
Conclusion: Comorbid liver cirrhosis and a drained liver volume < 50% contributed
significantly to ineffective drainage in the initial transpapillary USEMS
placements for UMHBSs.
PMID- 29963272
TI - The organic ester O,O'-diethyl-(S,S)-ethylenediamine-N,N'-di-2-(3
cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and
metastasis.
AB - Pharmacological treatment of cancer is mostly limited by drug-toxicity and
resistance. It has been noticed that new organic ester ligand, O,O'-diethyl-(S,S)
ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochloride (named DE
EDCP) showed effective cytotoxic capacities against several human and mouse
cancer cell lines. However, its effects on tumor growth and metastasis are
unexplored. The aim of present study was to examine the ability of DE-EDCP to
inhibit 4T1 murine breast cancer growth and progression and to explore possible
molecular mechanisms. DE-EDCP exhibited significant tumoricidal activity on human
and murine breast cancer cell lines. Further, marked reduction of murine breast
cancer growth and progression by DE-EDCP was shown. DE-EDCP exhibits fewer side
effects compared to cisplatin as a conventional chemotherapeutic. Results
obtained from in vivo and in vitro experiments indicate that DE-EDCP induces
apoptosis and inhibits proliferation of 4T1 cells. DE-EDCP increases percentage
of 4T1 cells in late apoptosis, expression of pro-apoptotic Bax and caspase-3,
while decreases expression of anti-apoptotic Bcl-2. DE-EDCP treatment increased
the percentage of TUNEL-positive nuclei and reduced Ki-67 expression in breast
cancer tissue. DE-EDCP decreased expression of cyclin D3 and Ki-67, increased
expression of cyclin-dependent kinase inhibitors p16, p21 and p27 and arrested
4T1 cells in G0/G1 cell cycle phase. Expression of STAT3 and downstream regulated
molecules, NANOG and SOX2, was reduced in 4T1 cells after DE-EDCP treatment. In
conclusion, DE-EDCP impairs breast cancer growth and progression by triggering
cancer cell death and inhibition of cancer cell proliferation. DE-EDCP might be
of interest in the development of the new anticancer agent.
PMID- 29963273
TI - Subcellular localization of MCM2 correlates with the prognosis of ovarian clear
cell carcinoma.
AB - Highly malignant tumors overexpress the minichromosome maintenance 2 (MCM2)
protein in the nucleus, which is associated with advanced tumor grade, advanced
stage, and poor prognosis. In this study, we showed that MCM2 is highly expressed
in clinical samples of ovarian clear cell carcinoma. Although MCM2 expression was
mainly localized to the nuclei as in other cancers, a few cases exhibited
cytoplasmic localization of MCM2. Surprisingly, tumor samples with cytoplasmic
MCM2 demonstrated excellent prognosis, showing 100% survival during the
observation period of more than 200 months. However, cases with nuclear
expression of MCM2 exhibited approximately 78% 5-year-survival rate. In a
previous study, we showed that Friend leukemia virus (FLV) envelope protein gp70
bound to MCM2, impaired its nuclear translocation, and enhanced DNA damage
induced apoptosis in FLV-infected hematopoietic cells with high levels of MCM2.
As expected, clear cell carcinoma cells with cytoplasmic expression of MCM2
exhibited significantly higher apoptotic cell ratio than that of cells with
nuclear MCM2 expression. In vitro experiments using ovarian cancer cells with
cytoplasmic expression of MCM2 demonstrated that transfection of MCM2-DeltaN
enhanced DNA damage-induced apoptosis. Therefore, cytoplasmic localization of
MCM2 significantly correlated with increased apoptosis in clear cell carcinoma
cells, resulting in improved prognosis.
PMID- 29963274
TI - Evaluation of effectiveness of granulocyte-macrophage colony-stimulating factor
therapy to cancer patients after chemotherapy: a meta-analysis.
AB - The impact of granulocyte-macrophage colony stimulating factor (GM-CSF) on
hematologic indexes and complications remains existing contradictory evidence in
cancer patients after treatment of chemotherapy. Eligible studies up to March
2017 were searched and reviewed from PubMed and Wanfang databases. Totally 1043
cancer patients from 15 studies were included in our research. The result
indicated that GM-CSF could significantly improve white blood cells count (SMD =
1.16, 95% CI: 0.71 - 1.61, Z = 5.03, P < 0.00001) and reduce the time to
leukopenia recovery (SMD = -0.85, 95% CI: -1.16 - -0.54, Z = 5.38, P < 0.00001)
in cancer patients after treatment of chemotherapy. It also could improve
absolute neutrophil count (SMD = 1.11, 95% CI: 0.39 - 1.82, Z = 3.04, P = 0.002)
and significantly shorten the time to neutropenia recovery (SMD = -1.47, 95% CI:
2.20 - -1.75, Z = 3.99, P < 0.0001). However, GM-CSF could not improve blood
platelet (SMD = 0.46, 95% CI: -0.37 - -1.29, Z = 1.10, P = 0.27). And GM-CSF had
significant connection with fever (RR = 3.44, 95% CI: 1.43 - 8.28, Z = 2.76, P =
0.006). The publication bias existed in the data of the impact of GM-CSF on blood
platelet and complication. In conclusions, GM-CSF had an intimate association
with some hematologic indexes and complications. Our study suggested that more
hematological indexes and even more other indexes need to be observed in future
studies.
PMID- 29963275
TI - Pharmacotherapies to tics: a systematic review.
AB - The efficacy of all pharmacotherapies for patients suffering from tics were
unclear. Literatures were searched from Medline, Embase, The Cochrane Library,
and four Chinese databases. The primary efficacy outcome scale was defined as the
Yale Global Tic Severity Scale (YGTSS). Overall estimates of pooled weighted mean
difference (WMD) with 95% confidence interval (CI) were calculated for each
outcome measure. A total of 53 trials were included. Meta-analysis suggested that
alpha-2 adrenergic agonist agents and atypical antipsychotic agents were
effective in improving tics, which included the maximum number of trials. Typical
antipsychotic agents were associated with severer side-effects than alpha-2
adrenergic agonist agents. Besides, Traditional Chinese Medicine showed positive
effects in YGTSS (NingDong Granule: WMD=-7.100, 95% CI, -10.430- -3.770; 5-Ling
Granule: WMD=-11.300, 95% CI, -14.208- -8.392), while glutamate modulators (D
serine, N-Acetylcysteine and riluzole) might not be working. In summary, alpha-2
adrenergic agonist agents were associated with the optimal weigh between efficacy
and safety. However, the significant factor of limited trials and sample sizes
discounted these findings. Further better studies are necessary to ascertain
them.
PMID- 29963276
TI - Tourniquet-ALPPS is a promising treatment for very large hepatocellular carcinoma
and intrahepatic cholangiocarcinoma.
AB - When very large hepatocellular carcinomas (HCCs) and intrahepatic
cholangiocarcinoma (IHCCs) with insufficient future liver remnants are treated
using associating liver partition and portal vein ligation for staged hepatectomy
(ALPPS), the outcome is often poor. We therefore tested the efficacy of a
modified version of that technique, tourniquet-ALPPS. A review of the literature
examining outcomes of HCC and IHCC patients treated with ALPPS revealed the
incidences of morbidity >= III and postoperative mortality to be respectively
20.7% and 16.1% among HCC patients and 50% and 45.4% among IHCC patients. In the
present case series, in which HCC and IHCC patients were treated with tourniquet
ALPPS, median tumor size was 100 mm (range: 70-200 mm). After surgical stage I,
there was no morbidity, no mortality and the median future liver remnant had
increased at day 7 by 76%. In surgical stage II, 100% of tumors were resectable
(8 right trisectionectomies, 5 with inferior vena cava resection). Two patients
experienced serious morbidity >= IIIB and 1 patient died (11%). One- and 3-year
overall survival was 75% and 60%, respectively. Thus tourniquet-ALPPS appears to
be an effective alternative to classical ALPPS for the treatment of patients with
HCC or IHCC.
PMID- 29963277
TI - Posterior reversible encephalopathy syndrome and takotsubo cardiomyopathy
associated with lenvatinib therapy for thyroid cancer: a case report and review.
AB - As immunotherapies including tyrosine kinase inhibitors become more widely used
for the treatment of a variety of malignancies, it is important for prescribers
and patients to understand the potential adverse effects associated with these
drugs. It is especially important to understand the potentially fatal side
effects associated with these drugs to further determine risk factors for their
development. The review presents a case of posterior reversible encephalopathy
syndrome with concomitant Takotsubo cardiomyopathy, associated with use of
lenvatinib therapy for thyroid cancer. It discusses the interventions performed
and outcome. Potential mechanisms for development of these rare adverse effects,
as well as cases in which these adverse effects are seen with use of other
tyrosine-kinase inhibitors will be presented. It is important to continue to
report these side effects, and further studies are needed to elucidate potential
risk factors for their development, as well as to determine prognosis after
development.
PMID- 29963278
TI - Correction: Systematic identification and comparison of expressed profiles of
lncRNAs and circRNAs with associated co-expression and ceRNA networks in mouse
germline stem cells.
AB - [This corrects the article DOI: 10.18632/oncotarget.15719.].
PMID- 29963279
TI - Correction: Caveolin-1-mediated STAT3 activation determines electrotaxis of human
lung cancer cells.
AB - [This corrects the article DOI: 10.18632/oncotarget.21306.].
PMID- 29963280
TI - A Computational Study of Expressive Facial Dynamics in Children with Autism.
AB - Several studies have established that facial expressions of children with autism
are often perceived as atypical, awkward or less engaging by typical adult
observers. Despite this clear deficit in the quality of facial expression
production, very little is understood about its underlying mechanisms and
characteristics. This paper takes a computational approach to studying details of
facial expressions of children with high functioning autism (HFA). The objective
is to uncover those characteristics of facial expressions, notably distinct from
those in typically developing children, and which are otherwise difficult to
detect by visual inspection. We use motion capture data obtained from subjects
with HFA and typically developing subjects while they produced various facial
expressions. This data is analyzed to investigate how the overall and local
facial dynamics of children with HFA differ from their typically developing
peers. Our major observations include reduced complexity in the dynamic facial
behavior of the HFA group arising primarily from the eye region.
PMID- 29963281
TI - Prescription audit in a paediatric sickle cell clinic in South-West Nigeria: A
cross-sectional retrospective study.
AB - Background: Sickle cell disease (SCD) is a genetic haematological disorder that
affects millions of people around the world especially people of African
heritage. The treatment of the symptoms of SCD includes the use of analgesics,
antibiotics, and anti-malarial drugs. Studying the pattern of drug prescription
is a veritable tool for establishing the current practice and how it conforms to
existing guidelines. Objectives: The main objective of this study was to assess
the pattern of drug prescription in children with sickle cell disease (SCD)
attending the paediatric outpatients' clinic of a tertiary care centre in Ado
Ekiti, South-West Nigeria. Methods: This was a cross-sectional retrospective
study carried out using the medical records of all patients with SCD who attended
the paediatric outpatient clinic of the teaching hospital between January 1 and
December 31, 2014. The information retrieved from the case notes included the bio
demographic data, associated co-morbid conditions and the list of prescribed
drugs. Results: A total of 202 SCD patients aged below 18 years were seen in the
clinic during the study period with males accounting for 61.9% of them. The mean
age of all patients was 6.9 +/-3.8 yrs. A total of 1015 medications were
prescribed during the study period giving a mean of 5.02 +/- 1.9.
Vitamins/micronutrients, anti-malarial drugs, antibiotics and analgesics
accounted for 41.4%, 29.0%, 15.7% and 13.9% of all prescribed drugs respectively.
Antibiotics from the penicillin group were the most commonly prescribed followed
by macrolides and cephalosporins while Ibuprofen (60.3%) and Acetaminophen
(32.6%) were the commonly prescribed analgesics. Conclusion: High rate of
antibiotic prescription, low use of opioid analgesics and non-prescription of
prophylactic penicillin/pneumococcal vaccination were the main findings in this
study. There is need for the introduction of standard treatment protocols for
this group of patients.
PMID- 29963282
TI - Bacterial vaginosis: Prevalence and associated risk factors among non-pregnant
women of reproductive age attending a Nigerian tertiary hospital.
AB - Aim: To determine the prevalence and risk factors associated with bacterial
vaginosis (BV) among non-pregnant women of reproductive age group. Methods: A
cross-sectional study among non-pregnant asymptomatic women aged 19 to 45 years,
attending the gynaecological clinic at University of Ilorin Teaching Hospital,
Ilorin, Nigeria. Participants were counselled and an informed consent was
obtained. This was followed by vaginal swabs for microscopy, culture and
sensitivity. Diagnosis of BV was by Nugent's criteria. Data analysis was by
Statistical Package for Social Sciences (SPSS) version 20.0. Chi-square and Yates
corrected chi-square were calculated, and p value <0.05 was significant. Results:
Among the 212 participants, prevalence of BV was 40.1%; it was common among women
aged 25-34 years (50; 58.8%), the married (77; 90.6%) and those with tertiary
education (39; 45.9%). The risk factors for BV were common among women with
laboratory evidence of the infection, however statistically significant risk
factors were the use of intrauterine device (OR 1.61, 95%CI 0.543-4.759; p0.020)
and previous voluntary termination of pregnancy (OR 1.04, 95%CI 0.600-1.808;
p0.047). Conclusion: There was high prevalence of bacterial vaginosis in the
study population. Universal screening and treatment of cases may assist in
lowering the associated morbidity.
PMID- 29963283
TI - Standard precaution knowledge and adherence: Do Doctors differ from Medical
Laboratory Scientists?
AB - Background: Doctors and laboratory scientists are at risk of infection from blood
borne pathogens during routine clinical duties. After over 20 years of standard
precautions, health care workers knowledge and compliance is not adequate. Aim:
This study is aimed at comparing adherence and knowledge of standard precautions
(SP) among Medical Laboratory Scientists (MLSs) and doctors. Methods: It was a
cross sectional study done at University of Nigeria Teaching Hospital,
ItukuOzalla. A semi structured pre-tested questionnaire was the study instrument.
Results: General knowledge of SP was high,76.2% in doctors and 67.6% in MLSs
although there were differences between the two groups on the knowledge of
components of SP. Safe injection practices, use of personal protective equipment
as well as safe handling of contaminated equipment or surfaces was higher amongst
doctors. Even though more than half of respondents in both groups, 53.1 % among
doctors and 58.1% among MLSs had received training on standard precautions, this
did not reflect in the practice. MLS reported more use of personal protective
equipment such as gloves and coveralls (100% in MLS and 35% of doctors), P<0.001.
Recapping of syringes was higher amongst doctors (63.6%) than MLS (55.1%).The
doctors practiced better hand hygiene than MLS (P<0.001). Constraints that
affected SP included non-availability of PPEs and emergency situations for both
groups. Conclusion: SP knowledge and practice are still low, and as such, there
is a need to train doctors and MLS on the components of SP. Policies on SP need
to be enforced and facilities for practice regularly supplied.
PMID- 29963284
TI - Road traffic collisions in Malawi: Trends and patterns of mortality on scene.
AB - Background: Worldwide, 90% of injury deaths occur in low- and middle-income
countries (LMIC). Road traffic collisions (RTCs) are increasingly common and
result in more death and disability in the developing world than in the developed
world. We aimed to examine the pre-hospital case fatality rate from RTCs in
Malawi. Material and Methods: A retrospective study was performed utilizing the
Malawian National Road Safety Council (NRSC) registry from 2008-2012. The NRSC
data were collected at the scene by police officers. Victim, vehicle, and
environmental factors were used to describe the characteristics of fatal
collisions. Case fatality rate was defined as the number of fatalities divided by
the number of people involved in RTCs each year. Logistic regression analysis was
used to determine predictors of crash scene fatality. Results: A total of 11,467
RTCs were reported by the NRSC between 2008 and 2012. Of these, 34% involved at
least one fatality at the scene. The average age of fatalities was 32 years and
82% were male. Drivers of motor vehicles had the lowest odds of mortality
following RTCs. Compared to drivers; pedestrians had the highest odds of
mortality (OR 39, 95% CI 34, 45) followed by bicyclists (OR 26, 95% CI 22, 31).
The average case fatality rate was 17% /year, and showed an increased throughout
the study period. Conclusions: RTCs are a common cause of injury in Malawi.
Approximately one-third of RTCs involved at least one death at the scene.
Pedestrians were particularly vulnerable, exhibiting very high odds of mortality
when involved in a road traffic collision. We encourage the use of these data to
develop strategies in LMIC countries to protect pedestrians and other road users
from RTCs.
PMID- 29963285
TI - Information management in Malawi's prevention of Mother-to-Child Transmission
(PMTCT) Program: Health workers' perspectives.
AB - Aim: Health workers are the key drivers for strengthening Prevention of Mother-to
Child Transmission (PMTCT) program information management in the health
facilities. Thus understanding how health workers perceive information management
can enlighten areas that require interventions to improve information management
processes in the health facilities. The purpose is to assess health workers'
perceptions toward PMTCT program information management and factors affecting
information management in the health facilities. Methods: The study was conducted
in five out of forty-three health facilities providing PMTCT services in Lilongwe
district and thirty out of sixty-eight health workers were recruited across the
study sites. Purposive and convenience sampling were used. Semi-structured
questionnaires and in-depth interviews were used to collect demographic
information and health workers' perceptions toward information management,
respectively. Thematic and content analysis techniques were employed for
qualitative data, while descriptive statistics were used for quantitative data.
Results: Most health workers perceived information management tasks as part of
their job description, but less important to provision of clinical services. For
many, use of information technology tools was viewed as beneficial and valuable,
whereas the paper-based system was perceived as tedious and difficult to manage.
In addition, some believed lack of feedback, information sharing, and poor
attitude toward information management tasks were challenges. Conclusion: Based
on the study findings, there is need to find ways of motivating data quality
improvement practises in the health facilities, as health workers view this as a
tangential, non-essential part of their job. Health facility leadership needs to
promote an information culture through enforcement of meetings, supervision and
provision of feedback. The government and its partners should continue rolling
out and enhancing competence of health workers on EMR in the health facilities
whilst also addressing challenges mentioned in the study.
PMID- 29963286
TI - Family medicine training and practice in Malawi: History, progress, and the
anticipated role of the family physician in the Malawian health system.
AB - This article analyses the development and implementation of family medicine
training and practice in Malawi, with special attention given to its current
status and the projected role the trained family physician will be expected to
play in the future. The general aim of the paper is to briefly review the role of
family physicians in rural areas, as well as to discuss the history of family
medicine training in Malawi. The idea of formal family medicine training and
practice in Malawi started as early as 2001 but did not come to fruition until
2011, with the start of the undergraduate clerkship in the fourth year of medical
school at the University Of Malawi College Of Medicine. This energy was followed
by the launch of a postgraduate training programme in early 2015. The challenges
encountered in this endeavour are also reviewed. The paper concludes by
discussing the expected role a Malawian family physician will play in the local
context, considering the key roles that family physicians play elsewhere in
Africa.
PMID- 29963287
TI - Proposing the LEGS framework to complement the WHO building blocks for
strengthening health systems: One needs a LEG to run an ethical, resilient system
for implementing health rights.
AB - The aim of this paper is to present a new framework to design and run a
responsive and resilient health system. It can be used by both private and
public, profit and non-profit organizations in order to translate strategic goals
of an organization into desirable and intended best practice, and results. This
includes the health sector. The framework is based on the four pillars of
leadership, ethics, governance and systems, hence called LEGS framework. It can
complement the six World Health Organization building blocks that guide inputs to
help a health system achieve the intended goals. Despite all the strengths of the
World Health Organization building blocks for health systems strengthening, it is
important to highlight a few challenges: Ethics is assumed but is not explicitly
stated as part of any building block. Furthermore, the World Health Organization
framework lacks the flexibility to accommodate other important factors which may
differ in various settings and contexts. Hence, the World Health Organization
building blocks are either difficult to apply or insufficient in certain
contexts, especially in countries with rampant corruption, weak rule of law and
systems. This paper explores areas to strengthen the existing framework so as to
achieve the intended results efficiently in different contexts. The authors
propose LEGS (Leadership, Ethics, Governance and Systems Framework). This
framework is very flexible, simple to use, easy to remember, accommodates the
existing six WHO building blocks and can better guide different health systems
and actors to achieve intended goals by taking into consideration the contextual
factors like deficits in moral capital, rule of law or socioeconomic determinants
of health.
PMID- 29963288
TI - Use of an electronic medical record to monitor efficacy of diabetes care in out
patients in a central hospital in Malawi: Patterns of glycaemic control and
lessons learned.
AB - The Malawian health sector has a strong tradition of systematic data collection
for monitoring and evaluation of large-scale services. A highly successful
adapted Directly Observed Treatment, Short course "DOTS" framework, based on
patient registers and paper-based mastercards was introduced to facilitate the
management and monitoring of the scale up of antiretroviral therapy.
Subsequently, a simple, touch-screen based electronic medical record system
(EMRs) was effectively introduced at high burden ART sites. Based on this model,
in 2010, a diabetes specific EMRs was introduced in the diabetes clinic at Queen
Elizabeth Central Hospital. In this paper we report on the first 3 years
experience with the diabetes EMRs. We highlight the strengths and weaknesses of
the diabetes EMRs and present data on glycaemic control recorded in the system.
PMID- 29963289
TI - North African physicians' perspectives on the challenges facing medical research.
PMID- 29963290
TI - Cryptococcal meningitis in a previously healthy child.
AB - An 8-year-old previously healthy female presented with a 3 weeks history of
headache, neck stiffness, deafness, fever and vomiting and was diagnosed with
cryptococcal meningitis. She had documented hearing loss and was referred to
tertiary-level care after treatment with fluconazole did not improve her
neurological signs and symptoms. Her symptoms slowly resolved over two months.
This case report illustrates the occurrence of cryptococcal meningitis in a non
immunocompromised patient, as well as the challenges of providing effective care
in resource-limited settings.
PMID- 29963291
TI - Evaluating mobile solutions of integrated Community Case Management (iCCM):
Making the final connection.
PMID- 29963292
TI - Profile Interview: Prof. Stephen Gordon.
PMID- 29963293
TI - Journal of Oral Microbiology extends its editorial competence in immunology
promoting its international impact.
PMID- 29963295
TI - Cost-effectiveness analysis of the human recombinant epidermal growth factor in
the management of patients with diabetic foot ulcers.
AB - Introduction: Diabetic foot ulcers are one of the most frequent complications of
diabetes; such ulcers cause an increase in the costs of the health care of the
diabetic patient and can even cause disability due to amputation in the patient.
Although a proportion of patients achieve a spontaneous closure of ulcers, others
require medical or surgical treatment. Objective: To determine the cost
effectiveness of the intra- and perilesional application of recombinant human
epidermal growth factor (rhEGF), as opposed to conventional therapy for the
management of patients diagnosed with Wagner's 3 or 4 diabetic foot ulcer in
Colombia. Methodology: Using a Markov model, the process of care of a diabetic
patient with diagnosis of Wagner's 3 or 4 ulcer receiving conventional treatment,
or intra- and perilesional rhEGF, is configured. The evaluation cycles of the
treatments are weekly over a 5-year horizon and the outcomes evaluated are
quality-adjusted life years (QALYs) and the number of amputations avoided by each
treatment scheme, in addition to the total costs for treatments. Results: For the
analysed base case, in the outcome of amputations, it was found that the factor
presents 39 fewer amputations, in a cohort of 100 patients, compared with
conventional treatment. Likewise, QALYs are 0.65 more with the use of rhEGF in an
average patient. The estimated cost-utility ratio for the base case would be
below the threshold established for Colombia. Conclusions: The intra- and
perilesional application of rhEGF is a more effective therapeutic option than
conventional therapy in the treatment of patients with Wagner's 3 or 4 diabetic
foot ulcers and is cost-effective, taking as an outcome the QALYs for Colombia
from the perspective of the health system.
PMID- 29963296
TI - The psychotherapeutic care of refugees in Europe: treatment needs, delivery
reality and recommendations for action.
AB - The special issue of the European Journal of Psychotraumatology released on 7
November 2017 focused on traumatized refugees and on the mental health burden,
screening instruments and interventions in different groups of refugees. This
contribution takes up this discussion on the needs and challenges for mental
healthcare of traumatized refugees from the point of view of the practitioners.
It reports on the findings of a survey on the treatment situation and the
delivery reality of healthcare for refugees in 14 European countries, identifies
treatment gaps, and sets recommendations for action at the political and
therapeutic levels. The survey was conducted by the Federal Chamber of
Psychotherapists with the assistance of the Network for Psychotherapeutic Care in
Europe. The findings underline the need for appropriate mental healthcare for
this population.
PMID- 29963294
TI - Citrullination as a plausible link to periodontitis, rheumatoid arthritis,
atherosclerosis and Alzheimer's disease.
AB - Periodontitis, rheumatoid arthritis (RA), atherosclerosis (AS), and Alzheimer's
disease (AD) are examples of complex human diseases with chronic inflammatory
components in their etiologies. The initial trigger of inflammation that
progresses to these diseases remains unresolved. Porphyromonas gingivalis is
unique in its ability to secrete the P. gingivalis-derived peptidyl arginine
deiminase (PPAD) and consequently offers a plausible and exclusive link to these
diseases through enzymatic conversion of arginine to citrulline. Citrullination
is a post-translational enzymatic modification of arginine residues in proteins
formed as part of normal physiological processes. However, PPAD has the potential
to modify self (bacterial) and host proteins by deimination of arginine amino
acid residues, preferentially at the C-terminus. Migration of P. gingivalis
and/or its secreted PPAD into the bloodstream opens up the possibility that this
enzyme will citrullinate proteins at disparate body sites. Citrullination is
associated with the pathogenesis of multifactorial diseases such as RA and AD,
which have an elusive external perpetrator as they show epidemiological
associations with periodontitis. Therefore, PPAD deserves some prominence as an
external antigen, in at least, a subset of RA and AD cases, with as yet
unidentified, immune/genetic vulnerabilities.
PMID- 29963297
TI - Prevalence of Leptospira spp. and Seoul hantavirus in brown rats (Rattus
norvegicus) in four regions in the Netherlands, 2011-2015.
AB - BACKGROUND: Brown rats (Rattus norvegicus) may carry pathogens that can be a
risk for public health. Brown rats in the Netherlands were tested for the
zoonotic pathogens Leptospira spp. and Seoul hantavirus (SEOV), in order to
obtain insight in their prevalence. METHODS AND RESULTS: Cross-sectional
studies were performed at four locations from 2011 to 2015. The rats were tested
for Leptospira spp. using real-time PCR and/or culture resulting in a prevalence
ranging between 33-57%. Testing for SEOV was done through an adapted human Seoul
hantavirus ELISA and real-time RT-PCR. Although at several locations the ELISA
indicated presence of SEOV antibodies, none could be confirmed by focus reduction
neutralization testing. CONCLUSION: The results indicate a widespread presence
of Leptospira spp. in brown rats in the Netherlands, including areas with a low
leptospirosis incidence in humans. No evidence for circulation of SEOV was found
in this study.
PMID- 29963298
TI - Extracellular vesicles from endothelial progenitor cells promote thyroid follicle
formation.
AB - Organogenesis is a complex and dynamic process requiring reciprocal communication
between different cell types. In the thyroid, thyrocyte progenitors secrete the
angiocrine factor, VEGFA, to recruit endothelial cells. In return, endothelial
cells promote thyrocyte organisation into spherical follicular structures, which
are responsible for thyroid hormone synthesis and storage. Medium conditioned by
endothelial progenitor cells (EPCs) can promote follicle formation and lumen
expansion (i.e. folliculogenesis) in an ex vivo culture system of thyroid lobes.
Here, we postulated that endothelial cells instruct thyrocyte progenitors by
producing extracellular vesicles (EVs). We found that medium conditioned by EPCs
contain EVs with exosomal characteristics and that these vesicles can be
incorporated into thyrocyte progenitors. By mass spectrometry, laminin peptides
were abundantly identified in the EV preparations, probably co-sedimenting with
EVs. Laminin-alpha1 silencing in EPC abrogated the folliculogenic effect of EVs.
However, density gradient separation of EVs from laminins revealed that both EV
rich and laminin-rich fractions exhibited folliculogenic activity. In conclusion,
we suggest that endothelial cells can produce EVs favouring thyrocyte
organisation into follicles and lumen expansion, a mechanism promoted by laminin
alpha1.
PMID- 29963300
TI - Risk Factors Associated with Self-reported Sexually Transmitted Infections among
Postsecondary Students in Canada.
AB - Background: Despite major public health efforts in addressing the burden of
disease caused by sexually transmitted infections (STIs), rates among young
adults continue to rise in Canada. The purpose of the study was to examine the
prevalence and risk factors associated with acquiring STIs among postsecondary
students in Canada. Methods: A secondary analysis of the American College Health
Association-National College Health Assessment II-C Spring 2016 survey data (n =
43,780) was conducted. Sexually active participants (n = 28,831) were examined
for their demographics, sexual behavior, alcohol and marijuana use, testing for
human immunodeficiency virus (HIV), and human papillomavirus vaccination history.
These factors were analyzed to help identify their possible association with
acquiring an STI using logistic regression and multivariate modeling. Results:
Among the study participants, 3.88% had an STI, with the highest rates observed
among females and individuals aged 21-24 years old. Multivariate logistic
analysis showed that participants who engaged in anal intercourse within the past
30 days (odds ratio [OR] = 1.634; 95% confidence interval [CI], 1.343-1.988), had
four or more sexual partners in the last 12 months (OR = 4.223; 95% CI, 3.595
4.962), used marijuana within the past 30 days (OR = 1.641; 95% CI, 1.387-1.941),
and had ever been tested for HIV (OR = 3.008; 95% CI, 2.607-3.471) had greater
odds of acquiring an STI. Conclusions: The findings of this study highlight
certain high-risk behaviors that are strongly associated with acquiring an STI
among postsecondary students. Thus, efforts to design and deliver relevant
educational programming and health promotion initiatives for this particular
population are of utmost importance.
PMID- 29963301
TI - Strategies for Preventing Catheter-associated Urinary Tract Infections.
PMID- 29963299
TI - Enrichment of extracellular vesicles from human synovial fluid using size
exclusion chromatography.
AB - As a complex biological fluid, human synovial fluid (SF) presents challenges for
extracellular vesicle (EV) enrichment using standard methods. In this study of
human SF, a size exclusion chromatography (SEC)-based method of EV enrichment is
shown to deplete contaminants that remain after standard ultracentrifugation
based enrichment methods. Specifically, considerable levels of serum albumin, the
high-density lipoprotein marker, apolipoprotein A-I, fibronectin and other
extracellular proteins and debris are present in EVs prepared by differential
ultracentrifugation. While the addition of a sucrose density gradient
purification step improved purification quality, some contamination remained. In
contrast, using a SEC-based approach, SF EVs were efficiently separated from
serum albumin, apolipoprotein A-I and additional contaminating proteins that co
purified with high-speed centrifugation. Finally, using high-resolution mass
spectrometry analysis, we found that residual contaminants which remain after
SEC, such as fibronectin and other extracellular proteins, can be successfully
depleted by proteinase K. Taken together, our results highlight the limitations
of ultracentrifugation-based methods of EV isolation from complex biological
fluids and suggest that SEC can be used to obtain higher purity EV samples. In
this way, SEC-based methods are likely to be useful for identifying EV-enriched
components and improving understanding of EV function in disease.
PMID- 29963302
TI - Responsive brain stimulation in epilepsy.
AB - Stimulation devices are considered in patients with drug-resistant epilepsy and
who are not surgical candidates. Responsive neurostimulation (RNS) is a
cortically based stimulator activated by electrocorticography (ECoG) patterns.
Stimulation is applied directly to the seizure focus. The vagal nerve stimulator
AspireSR 106 is also a responsive device which, in addition to basal stimulation,
is activated by tachycardia. Deep brain stimulation of the anterior nucleus of
the thalamus is used in Europe for intractable epilepsy and yields similar
response rates to RNS using duty cycle stimulation. Chronic subthreshold cortical
stimulation is an experimental form of constant, low-level stimulation applied to
a seizure focus. These modalities are discussed and compared in this review.
PMID- 29963303
TI - Grafted Neural Stem Cells Show Lesion-Specific Migration in Radiation-Injured Rat
Brains.
AB - Neural stem cells (NSCs) exhibit preferential homing toward some types of brain
lesion, but their migratory property during radiation brain injury (RBI) remains
unexplored. Here, we use the superparamagnetic iron oxide (SPIO)-labeled magnetic
resonance imaging (MRI) technology to determine the migration of transplanted
NSCs in two partial RBI models in real time, created by administering 30-55 Gy of
radiation to the right or posterior half of the adult rat brain. SPIO-labeled
NSCs were stereotactically grafted into the uninjured side one week after RBI.
The migration of SPIO-labeled NSCs in live radiation-injured brains was traced by
MRI for up to 28 days after engraftment and quantified for their moving distances
and speeds. A high labeling efficiency (>90%) was achieved by incubating NSCs
with 100MUg/ml of SPIO for 12-24 hours. Upon stereotactic transplantation into
the healthy side of the brain, SPIO-labeled NSCs were distinctively detected as
hypointense signals on T2-weighted images (T2WI), showed sustained survival for
up to 4 weeks, and exhibited directional migration to the radiation-injured side
of the brain with a speed of 86-127 MUm/day. The moving kinetics of grafted NSCs
displayed no difference in brains receiving a high (55 Gy) vs. moderate (45 Gy)
dose of radiation, but was slower in the right RBI model than in the posterior
RBI model. This study shows that NSCs can be effectively labeled by SPIO and
traced in vivo by MRI, and that grafted NSCs exhibit directional migration toward
RBI sites in a route-dependent but radiation dose-independent manner.
PMID- 29963305
TI - Distribution and change of peroxynitrite in the guinea pig cochlea following
noise exposure.
AB - Nitric oxide (NO)-mediated pathology depends on the formation of reactive
intermediates, such as the peroxynitrite (ONOO-). ONOO- can nitrate free tyrosine
and tyrosine residues of proteins. Therefore, increases in tyrosine nitration
reflect the amount of ONOO- produced by oxidative stress. The distribution of 3
nitrotyrosine (3-NT), an ONOO- marker, in the organ of corti and the cochlear
lateral wall tissue from the guinea pig were examined using fluorescence
immunohistochemistry. The immunoactivity of 3-NT in the normal guinea pig was
compared with animals exposed to 122dBA broadband noise, 4 h/day, for 2
consecutive days. In the normal animals, 3-NT immunoreactivity was found in the
outer hair cells (OHCs), inner hair cells (IHCs), pillar cells (PCs), spiral
ganglion cells (SPCs) and the marginal cells of stria vascularis in the lateral
wall. Sound exposure increased the 3-NT signal in all of the cells and resulted
in extensive outer hair cell loss. A quantitative analysis of the 3-NT change in
OHCs and marginal cells of lateral wall showed that immunolabeling was
significant (P<0.01, n=10) in the noise exposure group compared with that of the
control group. Anti-3-NT and propidium iodide double labeling showed that 3-NT
was distributed mainly in the apical end of OHCs. In addition, 3-NT was
distributed outside of the nucleus of the OHCs and marginal cells. In conclusion,
the data indicate that noise exposure leads to a significant production of ONOO-
in the cochlear lateral wall and organ of corti. This is consistent with the
known increase of NO production by loud sound stress and suggests that NO-derived
free radicals participate in the cochlear pathophysiology of noise-induced
hearing loss.
PMID- 29963304
TI - Six novel susceptibility loci for coronary artery disease and cerebral infarction
identified by longitudinal exome-wide association studies in a Japanese
population.
AB - Coronary artery disease (CAD) and cerebral infarction (CI) remain major causes of
morbidity and mortality in humans. Recent genome-wide association studies have
identified various genetic variants associated with these diseases. However,
these studies were commonly conducted in a cross-sectional manner. Therefore, the
present research performed longitudinal exome-wide association studies for CAD
and CI using data on ~244,000 genotyped variants and the clinical data of 6,026
Japanese individuals who had attended annual health checkups for several years
(mean followed-up period, 5+/-3 years). Following quality controls, the
significance [false discovery rate (FDR) of <0.05] of association of the diseases
with 24,651 single nucleotide polymorphisms (SNPs) in 5,989 individuals for three
inheritance models was tested using the generalized estimating equation model.
SNPs that reached statistical significance were further screened against a
threshold of approxdf (a scale of small effective sample size) of >30. The
longitudinal exome-wide association studies revealed that three SNPs [rs4606855
of ADGRE3 (P=2.5*10-6; FDR=0.031; approxdf=71), rs3746414 of ZFP64 (P=5.9*10-6;
FDR=0.048; approxdf=93) and rs7132908 of FAIM2 (P<2.0*10-16; FDR<4.9*10-12;
approxdf=65)] were significantly associated with the prevalence of CAD. A
different set of three SNPs [rs6580741 of FAM186A (P<2.0*10-16; FDR<4.9*10-12;
approxdf=48), rs1324015 of LINC00400 (P<2.0*10-16; FDR<4.9*10-12; approxdf=49)
and rs884205 of TNFRSF11A (P<2.0*10-16; FDR<4.9*10-12; approxdf=32)] was
significantly associated with CI. The comparison of disease incidence with these
SNPs demonstrated that all the minor alleles were associated with decreased
susceptibility to CAD or CI. In conclusion, six novel SNPs were identified as
susceptibility loci for CAD (rs4606855 of ADGRE3, rs3746414 of ZFP64, and
rs7132908 of FAIM2) or CI (rs6580741 of FAM186A, rs1324015 of LINC00400, and
rs884205 of TNFRSF11A).
PMID- 29963306
TI - MicroRNA array analysis of the regulation of microRNAs in rats exhibiting
hyperplasia of mammary glands.
AB - Hyperplasia of mammary glands (HMG) is also termed mammary dysplasia. In China,
the number of patients suffering from breast hyperplasia is increasing annually.
MicroRNAs (miRNAs; length, 19-24 nucleotides), a group of small endogenous non
coding RNAs, post-transcriptionally regulate gene expression via RNA interference
and gene silencing pathways. The cause of disease of HMG because remains unclear.
Thus, the aim of the present study was to establish comprehensive profile of drug
treatments following at different time intervals on rat models of differentially
expressed miRNAs, using miRNA microarray data. After scanning the chip, 13 up
regulated and 20 down-regulated miRNAs were identified. MiR-31 and miR-30
exhibited different expression levels between rats exhibiting mammary gland
hyperplasia treated with or without Jiedu Capsule water solution once a day for 4
weeks, and the two demonstrated a strong association with HMG and breast cancer.
Therefore, the functions of these miRNAs may provide the basis for further
investigation of HMG.
PMID- 29963308
TI - BJPsych Open editorial transition: opportunity, challenge and vision.
AB - : BJPsych Open enters its fourth year with a transition in leadership and a new
Editor-in-Chief (EIC). This editorial summarises the Journal's metrics through
its first 36 months, provides insights into the Journal's history and growth, and
shares the aspirations of the new EIC for BJPsych Open. Declaration of interest:
K.R.K. is Editor-in-Chief of BJPsych Open; he took no part in the peer-review of
this work.
PMID- 29963307
TI - EphrinB2 signalling modulates the neural differentiation of human dental pulp
stem cells.
AB - Dental pulp stem cells (DPSCs) originate from the embryonic neural crest and have
neurogenic potential. The present study investigated the roles of the forward and
reverse EphrinB2 signalling pathways during DPSC neurogenesis. Treatment of DPSCs
with recombinant EphrinB2-Fc protein over 7 days in a neural induction culture
resulted in significant downregulation of the following neural markers: betaIII
Tubulin, neural cell adhesion molecule (NCAM), nestin, neurogenin 2 (NGN2),
neurofilament medium polypeptide and Musashi1. Immunocytochemistry revealed that
EphrinB2-Fc-treated DPSCs exhibited more rounded morphologies with fewer neurite
outgrowths as well as reduced protein expression of betaIII-tubulin and NGN2.
Treatment of DPSCs with a peptide inhibitor specific to the EphB4 receptor
significantly upregulated expression of the neural markers microtubule-associated
protein 2, Musashi1, NGN2 and neuron-specific enolase, whereas treatment with a
peptide inhibitor specific to the EphB2 receptor exerted negligible effects on
neurogenesis. Transgenic expression of EphrinB2 in DPSCs resulted in significant
upregulation of Musashi1 and NCAM gene expression, while treatment of DPSCs with
recombinant EphB4-Fc protein led to significant upregulation of only Musashi1.
Thus, it may be concluded that stimulation of forward EphrinB2-EphB4 signalling
markedly inhibited neurogenesis in DPSCs, whereas suppression of this forward
signalling pathway with peptide inhibitor specific to EphB4 promoted
neurogenesis. Meanwhile, stimulation of reverse EphB4-EphrinB2 signalling only
marginally enhanced the neural differentiation of DPSCs. The present findings
indicate the potential application of peptide or small molecule inhibitors of
EphrinB2 forward signalling in neural tissue engineering with DPSCs.
PMID- 29963309
TI - Diversity and Antifungal Activity of Endophytic Fungi Associated with Camellia
oleifera.
AB - Endophytic fungi strains (n = 81) were isolated from the leaves, barks, and
fruits of Camellia oleifera from Hunan province (China) to delineate their
species composition and potential as biological control agents of C. oleifera
anthracnose. The fungi were identified by morphological and phylogenetic
analyses. Fungal colonization rates of the leaves, barks, and fruits were 58.02,
27.16, and 14.81%, respectively. The isolates were identified as 14 genera,
belonging to two subdivisions, Deuteromycotina and Ascomycotina; 87.65% of all
isolates belonged to Deuteromycotina. The dominant species, occurring with a high
relative frequency, were Pestalotiopsis sp. (14.81%), Penicillium sp. (14.81%),
and Fusarium sp. (12.35%). The Simpson's and Shannon's diversity indices revealed
the highest species diversity in the leaves, followed by the barks and fruits.
The similarity index for the leaves versus barks comparison was the highest,
indicating that the number of endophytic fungal species shared by the leaves and
barks was higher than barks and fruits or leaves and fruits. Based on the results
of dual culture experiments, only five strains exhibited antifungal activity
against C. oleifera anthracnose pathogen, with isolate ty-64 (Oidium sp.)
generating the broadest inhibition zones. Our results indicate that the
endophytes associated with C. oleifera could be employed as natural agents
controlling C. oleifera anthracnose.
PMID- 29963310
TI - Colletotrichum fructicola, a Member of Colletotrichum gloeosporioides sensu lato,
is the Causal Agent of Anthracnose and Soft Rot in Avocado Fruits cv. "Hass".
AB - The filamentous Ascomycota Colletotrichum gloeosporioides sensu lato is a fungus
that has been reported worldwide as a causal agent of anthracnose disease in
avocado and other crops. In Mexico, this species affects fruits from an early
stage of development in the orchard until the post-harvest stage. Although
fungicides are continuously applied to control Colletotrichum species, pericarp
cankers and soft rot mesocarp in fruits are still frequently observed.
Considering the lack of a precise description of the causative agent, the aim of
the current study was to determine the pathogens involved in this symptomatology.
Twenty-four isolates were consistently obtained from the pericarp of avocado
fruits cv. "Hass" collected in the central avocado-producing area of Mexico.
Morphological features such as colony growth, conidia size, and mycelial
appressorium were assessed. Bayesian multilocus phylogenetic analyses were
performed using amplified sequences of the internal transcribed spacer region of
the nuclear ribosomal DNA; actin, chitin synthase, glyceraldehyde-3-phosphate
dehydrogenase partial genes; and APn2-Mat1-2 intergenic spacer and mating type
Mat1-2 partial gene from the nine selected isolates. In addition, fruits were
inoculated with a conidial suspension and reproducible symptoms confirmed the
presence of Colletotrichum fructicola in this area. This pathogenic species can
now be added to those previously reported in the country, such as C. acutatum, C.
boninense, C. godetiae, C. gloeosporioides, and C. karstii. Disease management
programs to reduce the incidence of anthracnose should include C. fructicola to
determine its response to fungicides that are routinely applied, considering that
the appearance of new species is affecting the commercial quality of the fruits
and shifting the original population structure.
PMID- 29963311
TI - Revision of the Lichen Genus Stereocaulon (Stereocaulaceae, Ascomycota) in South
Korea.
AB - Lichen genus Stereocaulon (Schreb.) Hoffm is distributed throughout the world.
Although 15 Stereocaulon species have been recorded in Korea, no detailed
taxonomic or revisionary research has been conducted for nearly two decades. In
this study, we collected 260 putative Stereocaulon spp. samples and identified
the species based on morphological, chemical, and molecular characteristics. From
the collected samples, 10 species of Stereocaulon were identified, nine of which
had already been reported, although this was the first report for the tenth, S.
octomerellum Hue, in Korea. General characteristics of Stereocaulon spp. include
coralloid phyllocladia and tubercular cephalodia; however, the specimen first
collected in Korea was a rare species with tomentum on the pseudopodetia. The
specimen of S. octomerellum is characterized by the presence of a primary
thallus, granule to short coralloid phyllocladia, and pseudopodetia up to 1 cm in
size, with tubercular cephalodia. To determine the phylogeny of the specimens, we
compared the ITS sequences of ribosomal DNA and the beta-tubulin gene sequences.
Phylogenetic analysis showed that the Korean Stereocaulon species were
monophyletic and placed in the previous phylogenetic classification. Species of
S. intermedium and S. exutum, however, were polyphyletic, and are morphologically
variable and widespread species. Overall, we present here detailed morphological
and chemical descriptions of each species identified and a revised key of all
known Stereocaulon species in South Korea.
PMID- 29963312
TI - Mon1 Is Essential for Fungal Virulence and Stress Survival in Cryptococcus
neoformans.
AB - Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab
GTPase and is essential for vacuole trafficking and autophagy in eukaryotic
organisms. Here, we identified and characterized the function of Mon1, an
ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen,
Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal
stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and
endoplasmic reticulum stress. However, the mon1 deletion mutant showed more
resistance to the antifungal agent fluconazole. In vivo studies demonstrated that
compared to the wild-type strain, the mon1 deletion mutant attenuated virulence
in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was
avirulent in the murine inhalation model. These results demonstrate that Mon1
plays a crucial role in stress survival and pathogenicity in C. neoformans.
PMID- 29963313
TI - Effects of Long-Term Subcultured Arbuscular Mycorrhizal Fungi on Red Pepper Plant
Growth and Soil Glomalin Content.
AB - Arbuscular mycorrhizal fungi (AMF) are well-known for their ability to improve
plant growth and help plants withstand abiotic stress conditions. Unlike other
fungi and bacteria, AMF cannot be stored, as they are obligate biotrophs. Long
term preservation of AMF spores is challenging and may lead to the loss of
viability and efficiency. This study aimed to understand the effect of prolonged
subculture of AMF species on the growth and glomalin-related soil protein (GRSP)
from red pepper (Capsicum annuum L.). AMF spores were mass-produced using
different techniques and subcultured in pots with sorghum sudangrass as the host
plant for 3 years. Experimental soil samples were collected from natural
grassland. Five different AMF inocula were used in triplicate as treatments.
After 70 days of growth, red pepper plants were harvested and plant dry weight,
plant nutrient content, mycorrhizal colonization, AMF spore count, and soil
glomalin content were determined. AMF-treated plants displayed higher dry weight
than controls, with only fruit dry weight being significantly different.
Similarly, significant differences in phosphorous and potassium contents of the
above-ground plant parts were observed between mycorrhizal and control
treatments. In addition, soil GRSP content was significantly higher in plants
inoculated with Rhizophagus sp. and Gigaspora margarita. The increased plant
growth and GRSP content suggest that AMF can be maintained for 3 years without
losing their efficiency if subcultured regularly with different symbiotic host
plants.
PMID- 29963314
TI - Biocontrol of Orchid-pathogenic Mold, Phytophthora palmivora, by Antifungal
Proteins from Pseudomonas aeruginosa RS1.
AB - Black rot disease in orchids is caused by the water mold Phytophthora palmivora.
To gain better biocontrol performance, several factors affecting growth and
antifungal substance production by Pseudomonas aeruginosa RS1 were verified.
These factors include type and pH of media, temperature, and time for antifungal
production. The results showed that the best conditions for P. aeruginosa RS1 to
produce the active compounds was cultivating the bacteria in Luria-Bertani medium
at pH 7.0 for 21 h at 37 degrees C. The culture filtrate was subjected to
stepwise ammonium sulfate precipitation. The precipitated proteins from the 40%
to 80% fraction showed antifungal activity and were further purified by column
chromatography. The eluted proteins from fractions 9-10 and 33-34 had the highest
antifungal activity at about 75% and 82% inhibition, respectively. SDS-PAGE
revealed that the 9-10 fraction contained mixed proteins with molecular weights
of 54 kDa, 32 kDa, and 20 kDa, while the 33-34 fraction contained mixed proteins
with molecular weights of 40 kDa, 32 kDa, and 29 kDa. Each band of the proteins
was analyzed by LC/MS to identify the protein. The result from Spectrum Modeler
indicated that these proteins were closed similarly to three groups of the
following proteins; catalase, chitin binding protein, and protease. Morphological
study under scanning electron microscopy demonstrated that the partially purified
proteins from P. aeruginosa RS1 caused abnormal growth and hypha elongation in P.
palmivora. The bacteria and/or these proteins may be useful for controlling black
rot disease caused by P. palmivora in orchid orchards.
PMID- 29963315
TI - Screening and Evaluation of Streptomyces Species as a Potential Biocontrol Agent
against a Wood Decay Fungus, Gloeophyllum trabeum.
AB - Two-hundred and fifty-five strains of actinomycetes isolated from soil samples
were screened for their antagonistic activities against four well-known wood
decay fungi (WDF), including a brown rot fungus, Gloeophyllum trabeum and three
white rot fungi Donkioporia expansa, Trametes versicolor, and Schizophyllum
commune. A dual culture assay using culture media supplemented with heated or
unheated culture filtrates of selected bacterial strains was used for the
detection of their antimicrobial activity against four WDF. It was shown that
Streptomyces atratus, S. tsukiyonensis, and Streptomyces sp. greatly inhibited
the mycelial growth of the WDF tested compared with the control. To evaluate the
biocontrol efficacy of S. atratus, S. tsukiyonensis, and Streptomyces sp., wood
blocks of Pinus densiflora inoculated with three selected Streptomyces isolates
were tested for weight loss, compression strength (perpendicular or parallel to
the grain), bending strength, and chemical component changes. Of these three
isolates used, Streptomyces sp. exhibited higher inhibitory activity against WDF,
especially G. trabeum, as observed in mechanical and chemical change analyses.
Scanning electron microscopy showed that cell walls of the wood block treated
with Streptomyces strains were thicker and collapsed to a lesser extent than
those of the non-treated control. Taken together, our findings indicate that
Streptomyces sp. exhibits the potential to be used as a biocontrol agent for wood
decay brown rot fungus that causes severe damage to coniferous woods.
PMID- 29963316
TI - Aspergillus terreus JF27 Promotes the Growth of Tomato Plants and Induces
Resistance against Pseudomonas syringae pv. tomato.
AB - Certain beneficial microorganisms isolated from rhizosphere soil promote plant
growth and induce resistance to a wide variety of plant pathogens. We obtained 49
fungal isolates from the rhizosphere soil of paprika plants, and selected 18 of
these isolates that did not inhibit tomato seed germination for further
investigation. Based on a seed germination assay, we selected four isolates for
further plant tests. Treatment of seeds with isolate JF27 promoted plant growth
in pot tests, and suppressed bacterial speck disease caused by Pseudomonas
syringae pathovar (pv.) tomato DC3000. Furthermore, expression of the
pathogenesis-related 1 (PR1) gene was higher in the leaves of tomato plants grown
from seeds treated with JF27; expression remained at a consistently higher level
than in the control plants for 12 h after pathogen infection. The phylogenetic
analysis of a partial internal transcribed spacer sequence and the beta-tubulin
gene identified isolate JF27 as Aspergillus terreus. Taken together, these
results suggest that A. terreus JF27 has potential as a growth promoter and could
be used to control bacterial speck disease by inducing resistance in tomato
plants.
PMID- 29963317
TI - First Report of Two Colletotrichum Species Associated with Bitter Rot on Apple
Fruit in Korea - C. fructicola and C. siamense.
AB - Bitter rot caused by the fungal genus Colletotrichum is a well-known, common
disease of apple and causes significant yield loss. In 2013, six fungal strains
were isolated from Fuji apple fruits exhibiting symptoms of bitter rot from
Andong, Korea. These strains were identified as Colletotrichum fructicola and C.
siamense based on morphological characteristics and multilocus sequence analysis
of the internal transcribed spacer rDNA, actin, calmodulin, chitin synthase, and
glyceraldehyde-3-phosphate dehydrogenase Pathogenicity tests confirmed the
involvement of C. fructicola and C. siamense in the development of disease
symptoms on apple fruits. This is the first report of C. fructicola and C.
siamense causing bitter rot on apple fruit in Korea.
PMID- 29963318
TI - Hyperlipidemic Inhibitory Effects of Phellinus pini in Rats Fed with a High Fat
and Cholesterol Diet.
AB - This study evaluated the in vitro and in vivo hypolipidemic effects of the
medicinal mushroom Phellinus pini. The methanol extract (ME) of the fruiting body
of Ph. pini was active against pancreatic lipase and cholesterol esterase with
99.14% and 67.23% inhibited activity at 1.0 mg/mL, respectively. It also
inhibited 81.81% and 55.33% of alpha-glucosidase and alpha-amylase activities,
respectively, at 2.0 mg/mL. Hyperlipidemia as induced by feeding rats with a high
fat and cholesterol diet (HFC). HFC supplemented with a 5% fruiting body powder
of Ph. pini (HFC + PhP) significantly reduced plasma total cholesterol, low
density lipoprotein cholesterol, and triglycerides in rats compared with HFC. The
reduced levels were comparable to rats fed the normal control diet (NC). The
atherogenic index of HFC + PhP rats was significantly lower than that of the HFC
rats. The excretion of fecal total lipid and cholesterol in the HFC + PhP rats
was significantly higher than those in the NC and HFC rats. Histopathological
examinations demonstrated scant deposition of lipids in the liver of rats fed HFC
+ PhP. The dietary supplementation with the fruiting body powder provided natural
plasma lipid and glucose lowering effects in experimental rats without adverse
effects on the plasma biochemical parameters and liver function related enzyme
activities. Therefore, the hypolipidemic effects of Ph. pini may be due to the
inhibitory effects on pancreatic lipase, cholesterol esterase, alpha-glucosidase,
and alpha-amylase, and excretion of excess lipids and cholesterol in the feces.
PMID- 29963319
TI - Identification and Characterization of Alternaria iridiaustralis Causing Leaf
Spot on Iris ensata in China.
AB - In 2016, a severe leaf spot disease was found on Iris ensata Thumb. in Nanjing,
China. The symptom was elliptical, fusiform, or irregularly necrotic lesion
surrounded by a yellow halo, from which a small-spored Alternaria species was
isolated. The fungus was identified as Alternaria iridiaustralis based on
morphological characteristics. The pathogenicity tests revealed that the fungus
was the causal pathogen of the disease. Phylogenic analyses using sequences of
ITS, gpd, endoPG, and RPB2 genes confirmed the morphological identification. This
study is the first report of A. iridiaustralis causing leaf spots on I. ensata in
China.
PMID- 29963320
TI - Alternaria brassicifolii sp. nov. Isolated from Brassica rapa subsp. pekinensis
in Korea.
AB - A new species belonging to the genus Alternaria was isolated from the necrotic
leaf spots of Brassica rapa subsp. pekinensis in Yuseong district, Daejeon,
Korea. It is an occasional isolate, not an etiological agent, which is
morphologically similar to A. broccoli-italicae, but differs in conidial size and
conidiophore shape. Phylogenetic analysis using the sequence datasets of the
internal transcribed spacer (ITS) region of the rDNA, glyceraldehyde-3-phosphate
dehydrogenase (gpd), and plasma membrane ATPase genes showed that it is distantly
related to A. broccoli-italicae and closely related to Alternaria species in the
section Pseudoalternaria, which belonged to a clade basal to the section
Infectoriae. Morphologically, the species is unique because it produces solitary
conidia or conidial chains (two units), unlike the four members in the section
Pseudoalternaria that produce conidia as short branched chains. It exhibits weak
pathogenicity in the host plant. This report includes the description and
illustration of A. brassicifolii as a new species.
PMID- 29963323
TI - Detecting cell-secreted growth factors in microfluidic devices using bead-based
biosensors.
AB - Microfluidic systems provide an interesting alternative to standard macroscale
cell cultures due to the decrease in the number of cells and reagents as well as
the improved physiology of cells confined to small volumes. However, the tools
available for cell-secreted molecules inside microfluidic devices remain limited.
In this paper, we describe an integrated microsystem composed of a microfluidic
device and a fluorescent microbead-based assay for the detection of the
hepatocyte growth factor (HGF) and the transforming growth factor (TGF)-beta1
secreted by primary hepatocytes. This microfluidic system is designed to separate
a cell culture chamber from sensing chambers using a permeable hydrogel barrier.
Cell-secreted HGF and TGF-beta1 diffuse through the hydrogel barrier into
adjacent sensing channels and are detected using fluorescent microbead-based
sensors. The specificity of sensing microbeads is defined by the choice of
antibodies; therefore, our microfluidic culture system and sensing microbeads may
be applied to a variety of cells and cell-secreted factors.
PMID- 29963322
TI - Quantitative analysis of focal adhesion dynamics using photonic resonator
outcoupler microscopy (PROM).
AB - Focal adhesions are critical cell membrane components that regulate adhesion and
migration and have cluster dimensions that correlate closely with adhesion
engagement and migration speed. We utilized a label-free approach for dynamic,
long-term, quantitative imaging of cell-surface interactions called photonic
resonator outcoupler microscopy (PROM) in which membrane-associated protein
aggregates outcoupled photons from the resonant evanescent field of a photonic
crystal biosensor, resulting in a highly localized reduction of the reflected
light intensity. By mapping the changes in the resonant reflected peak intensity
from the biosensor surface, we demonstrate the ability of PROM to detect focal
adhesion dimensions. Similar spatial distributions can be observed between PROM
images and fluorescence-labeled images of focal adhesion areas in dental
epithelial stem cells. In particular, we demonstrate that cell-surface contacts
and focal adhesion formation can be imaged by two orthogonal label-free
modalities in PROM simultaneously, providing a general-purpose tool for kinetic,
high axial-resolution monitoring of cell interactions with basement membranes.
PMID- 29963324
TI - Single-session percutaneous embolization with onyx and coils of sinus pericranii.
AB - Background: Sinus pericranii (SP) is a rare vascular malformation consisting of
an abnormal communication between the extra- and the intracranial venous system.
It occurs due to the adhesion of vessels without a muscular layer or a hemangioma
on the outer surface of the skull through diploic vessels, communicating with an
intracranial venous sinus. Case Description: A 10-month-old female presented with
a pulsatile mass on the posterior parietal region. Investigation with brain
vascular examinations showed a venous malformation communicating with the
superior sagittal sinus under the scalp, without arterial feeder or nidus. An
endovascular embolization with coils and a percutaneous embolization with Onyx
(r) were performed. The final venography showed complete exclusion of the lesion,
which was gradually being absorbed. Conclusion: This is the first case of an SP
successfully treated in a single session by embolization with coils and onyx.
PMID- 29963321
TI - Peptides as drug delivery vehicles across biological barriers.
AB - Peptides are small biological molecules that are attractive in drug delivery and
materials engineering for applications including therapeutics, molecular building
blocks and cell-targeting ligands. Peptides are small but can possess complexity
and functionality as larger proteins. Due to their intrinsic properties, peptides
are able to overcome the physiological and transport barriers presented by
diseases. In this review, we discuss the progress of identifying and using
peptides to shuttle across biological barriers and facilitate transport of drugs
and drug delivery systems for improved therapy. Here, the focus of this review is
on rationally designed, phage display peptides, and even endogenous peptides as
carriers to penetrate biological barriers, specifically the blood-brain
barrier(BBB), the gastrointestinal tract (GI), and the solid tumor
microenvironment (T). We will discuss recent advances of peptides as drug
carriers in these biological environments. From these findings, challenges and
potential opportunities to iterate and improve peptide-based approaches will be
discussed to translate their promise towards the clinic to deliver drugs for
therapeutic efficacy.
PMID- 29963325
TI - Minimally invasive spine surgery in the pediatric and adolescent population: A
case series.
AB - Background: There is scant literature evaluating the indications, techniques, and
outcomes of minimally invasive spine (MIS) surgery undertaken for pediatric and
adolescent spine pathology. Our study attempts to evaluate the safe and effective
use of MIS techniques in pediatric and adolescent patients and to appreciate the
technical nuances of MIS surgery for this age group. Methods: Consecutive
pediatric and adolescent patients undergoing elective MIS lumbar procedures, from
2008 to 2016, were retrospectively analyzed from the practice of a single
fellowship-trained academic spinal neurosurgeon. Information was retrieved
regarding procedure and disease pathology. Descriptive data was obtained
including age, sex, body mass index (BMI), insurance coverage, smoking status,
and co-morbidities. Outcome measures were recorded including intraoperative
complications, revision surgery, and return-to-function. Results: Sixteen
patients underwent 17 surgeries. The median BMI was 29.2 (range, 20.8-41.5). Age
ranged from 12 to 19 years. Nearly 20% of the patients in our series were
smokers. Most patients underwent discectomy, with L5-S1 being the most common
level. One patient underwent direct pars defect repair and another underwent
recurrent discectomy. More than 90% of the patients were complication-free at
follow-up period of 6 months. One patient had a recurrent disc herniation and
another had a superficial wound infection. Overall, 82.4% patients enjoyed full
return to sports such as weight lifting, gymnastics, and contact sports. One
patient required pain management to help alleviate ongoing pain. Another patient
required a course of outpatient rehabilitation to help with a "foot drop."
Conclusion: Our series illustrates the effective application of MIS techniques
among carefully selected pediatric patients. Emphasis is on using a smaller (16
mm) tubular retractor and causing minimal disruption of paraspinal osseo
tendinous structures. MIS techniques can be successfully applied to the pediatric
and adolescent age group.
PMID- 29963326
TI - Surgical removal of an arteriovenous malformation in the anterior perforated
substance in a pregnant woman.
AB - Background: A tailor-made treatment is often required in arteriovenous
malformations (AVMs) depending on the individual situation. In most cases,
treatment strategy is usually determined according to the patient's Spetzler
Martin grade. However, in the present case, we were not able to treat the patient
following the usual guidelines because of neurological symptoms and pregnancy.
Case Description: We describe a rare case of a 31-year-old woman in the 15th week
of gestation who presented with an AVM in the anterior perforated substance
(APS). She suffered a sudden coma and hemiplegia. A computed tomographic scan
showed an enhanced mass and a huge hematoma in the basal ganglia and temporal
lobe. The hematoma was successfully evacuated in an endoscopic procedure.
Angiography showed that a 25-mm nidus in the APS was fed by the anterior
choroidal arteries (AChAs) and the lenticulostriate arteries (LSAs). Therefore,
we attempted to remove the nidus because the patient became alert with mild
aphasia and hemiparesis 10 days after hemorrhage. The feeding arteries were cut
under motor evoked potential (MEP) monitoring, and the nidus was totally resected
leaving two of four AChAs and a single artery with several LSAs. The
postoperative course was uneventful, and she gave birth to a healthy baby by
caesarian delivery 122 days after the hemorrhage with only minor sequelae.
Conclusions: Surgical strategy with a device-administered anesthesia are suitable
for removing large AVMs even in pregnant women and for the successful outcome of
their pregnancies. Even after recovering from a coma and hemiplegia, MEP
monitoring is effective for removing large AVMs even when located in the APS.
PMID- 29963327
TI - Role of point of care Hb diagnostic devices in getting the right picture of
anemia control: Tangi Rural Anemia Diagnostic Accuracy Study.
AB - Objectives: To study the accuracy and reliability of two point of care devices
(Hemocue 201 [HC201]) and Hemoglobin Colour Scale (HCS) with reference to
automated laboratory analyser Sysmex XP 100 (LabSXP) and determine factors
influencing their performances. To discuss certain design issues while
ascertaining these parameters for its judicious use in both clinical context and
disease burden studies. Methods: Reliability and accuracy statistics were
calculated for four population subgroups that were selected randomly using
cluster sampling in a rural community of eastern India. Appropriate measures were
taken to reduce biases in the study. Bland Altmann Plot was used to determine
Bias and ROC curve analysis was used to suggest new cut-offs for HCS method.
Results: True prevalence varied across subgroups ranging from 12.56% in
adolescent boys to 40.71% in adult women. Sensitivity for HC201 was lowest among
boys (80.39%) and highest among adult females (92.82%), while specificity was
highest among adult males (86.94%) and lowest among adult females (75.00%). The
variation across subgroups was due to differences in distribution of underlying
Hb values. HC201 has potential for use in clinical practice as well as disease
burden estimation study. HCS was not suitable for use in clinical setting as the
bias (-4.1 g/dl) was unacceptable. However, ROC analysis suggested certain cut
offs for different age groups and can be employed in poor resource settings for
disease burden estimation study. Conclusions: HC201 is better than HCS as per the
study. However, accuracy parameters are likely to vary depending on the
distribution of underlying Hb distribution. Thus, same machines can demonstrate
different accuracy parameters in different settings. There is need for designing
studies that could help estimate these parameters each time on a subsample which
would go a long way in efficiently using technology be it for guiding clinical
decisions or public health actions.
PMID- 29963328
TI - Benign Sclerosing and Fibrosing Conditions of the Abdomen and Their Potential
Mimics.
AB - The process of abnormal reparative or reactive processes in the abdominal cavity,
can lead to sclerosis and fibrous deposition. The relatively recent discovery of
an IgG4 subgroup of immune mediated sclerosing disease 1,2 has thrown some light
on the pathophysiology of these conditions. Firstly, our pictorial review aims to
describe imaging findings to enhance the general radiologist's recognition and
interpretation of this varied group of benign sclerotic and fibrotic abdominal
processes. Secondly, along with the imaging findings, we bring into discussion
the potential mimics of these pathologic processes to minimise interpretational
errors. Moreover, some of the mimics of these processes are in the spectrum of
malignant disease. Most importantly, to ensure a correct diagnosis thorough
clinical and histopathological assessment are required to support the imaging
findings presented in this review.
PMID- 29963330
TI - Protein Kinase C: The Drug Target One Must See.
PMID- 29963331
TI - Direct ATRP of Methacrylic Acid with Iron-Porphyrin Based Catalysts.
AB - An iron porphyrin catalyst, derived from the active center of proteins such as
horseradish peroxidase and hemoglobin, was successfully used for the atom
transfer radical polymerizations (ATRP) of methacrylic acid. ATRP of methacrylic
acid and other acidic monomers is challenging due to Cu complexation by
carboxylates, protonation of the ligand, and displacement of the halogen chain
end. A robust mesohemin-based catalyst provided controlled ATRP of methacrylic
acid, yielding poly(methacrylic acid) with Mn >= 20000 and dispersity D < 1.5.
Retention of halogen chain end was confirmed by successful chain extension of a
poly-(methacrylic acid)-Br macroinitiator.
PMID- 29963329
TI - Cell-type-specific brain methylomes profiled via ultralow-input microfluidics.
AB - Methylomic analyses typically require substantial amounts of DNA, thus hindering
studies involving scarce samples. Here, we show that microfluidic diffusion-based
reduced representative bisulfite sequencing (MID-RRBS) permits high-quality
methylomic profiling with nanogram-to-single-cell quantities of starting DNA. We
used the microfluidic device, which allows for efficient bisulfite conversion
with high DNA recovery, to analyse genome-wide DNA methylation in cell nuclei
isolated from mouse brains and sorted into NeuN+ (primarily neuronal) and NeuN-
(primarily glial) fractions, and to establish cell-type-specific methylomes.
Genome-wide methylation and methylation in low-CpG-density promoter regions
showed distinct patterns for NeuN+ and NeuN- fractions from the mouse cerebellum.
The identification of substantial variations in the methylomic landscapes of the
NeuN+ fraction of the frontal cortex of mice chronically treated with an atypical
antipsychotic drug suggests that this technology can be broadly used for cell
type-specific drug profiling and for the study of drug-methylome interactions.
PMID- 29963332
TI - The Lake-Catchment (LakeCat) Dataset: characterizing landscape features for lake
basins within the conterminous USA.
AB - Natural and human-related landscape features influence the ecology and water
quality of lakes. Summarizing these features in a hydrologically meaningful way
is critical to understanding and managing lake ecosystems. Such summaries are
often done by delineating watershed boundaries of individual lakes. However, many
technical challenges are associated with delineating hundreds or thousands of
lake watersheds at broad spatial extents. These challenges can limit the
application of analyses and models to new, unsampled locations. We present the
Lake-Catchment (LakeCat) Dataset (https://www.epa.gov/national-aquatic-resource
surveys/lakecat) of watershed features for 378,088 lakes within the conterminous
USA. We describe the methods we used to: 1) delineate lake catchments, 2)
hydrologically connect nested lake catchments, and 3) generate several hundred
watershed-level metrics that summarize both natural (e.g., soils, geology,
climate, and land cover) and anthropogenic (e.g., urbanization, agriculture, and
mines) features. We illustrate how this data set can be used with a random forest
model to predict the probability of lake eutrophication by combining LakeCat with
data from US Environmental Protection Agency's National Lakes Assessment (NLA).
This model correctly predicted the trophic state of 72% of NLA lakes, and we
applied the model to predict the probability of eutrophication at 297,071
unsampled lakes across the conterminous USA. The large suite of LakeCat metrics
could be used to improve analyses of lakes at broad spatial extents, improve the
applicability of analyses to unsampled lakes, and ultimately improve the
management of these important ecosystems.
PMID- 29963334
TI - Reproductive ecology of the endangered Beal's-eyed turtle, Sacalia bealei.
AB - The Beal's-eyed turtle (Sacalia bealei) is endemic to southeastern China and
endangered due to poaching and habitat loss. Knowledge of S. bealei ecology is
lacking and this study provides baseline information of its reproduction in a
natural environment. We studied the reproductive ecology of S. bealei using X
ray, spool-and-line tracking, and direct observation. Six nesting females were
successfully tracked and their nesting behaviors are documented in detail.
Females produced a mean clutch size of 2.2 eggs (range 1-3). The hard-shelled
eggs were ellipsoidal with a mean length of 45.50 mm, a mean width of 23.20 mm,
and mean weight of 14.8 g. The relative clutch mass was 9.47%, while the relative
egg mass was 4.60%. The mean incubation period was 94.7 days with a mean nest
temperature of 25.08 degrees C. Hatchlings had a mean weight of 9.7 g, carapace
length of 40.1 mm, carapace width of 33.3 mm, carapace height of 17.4 mm,
plastron length of 31.6 mm, and plastron width of 25.4 mm. The results of this
study provide important information to inform conservation plans and ex-situ
breeding for this endangered species.
PMID- 29963335
TI - Dose Reduction to the Scalp with Hippocampal Sparing Is Achievable with Intensity
Modulated Radiotherapy.
AB - We evaluated the feasibility of combined hippocampal- and scalp-sparing intensity
modulated radiotherapy (IMRT) plans. This study included 7 patients who received
conventional palliative whole brain radiation treatment (WBRT) for brain
metastasis. The brain, hippocampus, and scalp were contoured and replanned with
intensity modulated radiation therapy. The prescription dose was 30 Gray (Gy) in
10 fractions with hippocampus and normal structure constraints per the Radiation
Therapy Oncology Group (RTOG) 0933 protocol. Further planning was done to
minimize the scalp dose while maintaining the dose constraints for the
hippocampus. Dose volume histograms were obtained from conventional opposed
lateral fields, IMRT and compared. Planning target volume (PTV) coverage for all
plans fell within the RTOG 0933 critical structure acceptable variation category.
When compared to traditional opposed lateral fields, the IMRT plan with combined
hippocampal- and scalp-sparing constraints was able to significantly reduce the
max and mean scalp dose as well as the percentage of scalp receiving 10 and 20 Gy
by 46% and 35%, respectively, while maintaining acceptable RTOG 0933 hippocampal
dose variations. We conclude that acceptable PTV coverage and sparing of the
scalp and hippocampus can be accomplished using a 9-field non-coplanar IMRT plan.
Prospective study is warranted to understand the impact on radiation induced
alopecia.
PMID- 29963333
TI - Influences of Maternal Stress during Pregnancy on the Epi/genome: Comparison of
Placenta and Umbilical Cord Blood.
AB - Background: Maternal stress during pregnancy is one of the major adverse
environmental factors in utero that is capable of influencing health outcomes of
the offspring throughout life. Both genetic and epigenetic processes are
susceptible to environmental insults in utero and are potential biomarkers of the
experienced environment including maternal stress. Methods: We profiled
expression level of six genes in hypothalamic pituitary adrenal (HPA) axis
functioning (HSD11B2, SLC6A4, NR3C1, NR3C2, CRHR1 and CRHR2), two imprinted genes
(IGF2 and H19) and one neurodevelopmental gene (EGR1), from 49 pairs of placenta
and umbilical cord blood (UCB) samples from a birth cohort. We also assessed
global methylation levels by LUminometric Methylation Assay (LUMA) and
methylation at the imprinting control region (ICR) of IGF2/H19. Results: Little
correlations between paired placenta and UCB were observed except H19 expression
(r = 0.31, P = 0.04) and IGF2/H19 ICR methylation (r = 0.43, P = 0.01); gene
expression levels were significantly higher (P < 0.001) in placenta than UCB
except CRHR1 and CRHR2, which were unexpressed in placenta. Maternal stress
correlated higher levels of HPA genes and lower levels of EGR1 and LUMA, but only
in placenta. Positive association between maternal stress and IGF2/H19 ICR
methylation was present in both placenta and UCB. Conclusions: Our findings
support the notion that adverse in utero environment, as measured by antenatal
maternal stress, depression and anxiety, can be observed in the epi/genome of the
relevant tissues, i.e. placenta and UCBs, leading to development of molecular
markers for assessing in utero adversities.
PMID- 29963336
TI - Dosimetry and Treatment Descriptions Using the First Completely Automated
Stereotactic Intracranial Radiosurgery Rotating Gamma Ray Unit in America.
AB - Introduction The objective is to report the dosimetry and safety profiles of the
first fully automatized rotating gamma ray unit for intracranial radiosurgery in
America. Methods Dosimetry tests were conducted by our institution using the
standard of examination and calibration and the Intelligent gamma Radiometer of
the China Research Institute of Measurement. The phantom and dosimetry tests were
performed by the Outreach Physics Section of MD Anderson Cancer Center and the
Anchorage Radiation Therapy Center using the Radiation Therapy Oncology Group
(RTOG) radiosurgery quality assurance guidelines. Clinically, 233 patients were
treated. Results Mechanical precision was 0.16 mm and the offset registered at
the phantom on all axes was 0.0. The ratio of the dose to the center was 0.97
(0.95-1.05), the ratio of the treated volume was 0.95 (0.75-1.25), the ratio of
the measured treated volume to the volume of the target was 1.29 (1.00-2.00), the
ratio of the minimal dose to the dose prescribed was 1.05 (>0.90), with a treated
volume of 0.95 (0.75-1.25) and a minimum dose to target of 1.05 (>0.90). The dose
rate at loading was 3.89 Gy per minute. None of the patients treated experienced
severe complications. Conclusions The dosimetry studies are compliant with
quality assurance standards for intracranial radiosurgery.
PMID- 29963337
TI - A Novel Approach to Debriefing Medical Simulations: The Six Thinking Hats.
AB - Simulation has become a standard training method in emergency medicine (EM).
Specifically, post-simulation debriefings offer participants the opportunity for
reflection while exposing their knowledge and practice gaps. The educational
yield of these debriefings, however, is contingent on the debriefer's skills.
Without professional development, faculty and educators may not be equipped with
supportive debriefing strategies. We propose the Six Thinking Hats (6TH),
originally developed by Edward de Bono (1970) as a debriefing framework to
support effective, high-yield debriefing conversations. The six colored hats
represent six unique approaches to critical thinking. The white hat represents
the facts; the green hat, creativity and next steps; the yellow hat,
benefits/optimism; the red hat, emotions; the black hat, judgments; and the blue
hat, facilitation. Four junior faculty members underwent a one-hour didactic and
one-hour immersive workshop on the 6TH. Two simulation cases were randomly
selected from archived simulation cases, which were used for the debriefing
process. Each team consisted of one EM resident and one EM faculty. After each
simulated case, the facilitator introduced the 6TH at the start of the
debriefing, explaining the rules of engagement and the general sequence of hats
to be used. Physical hats were worn by the facilitator at the beginning of the
session and changed throughout stages of the debriefing, to remind participants
of the type of thinking that was taking place at any given time. Participants who
were provided with a colored hat prompt that physically described the type of
thinking being employed throughout stages of the debriefing were better able to
stay within that respective thinking frame during the discussion, compared to
participants who were not provided this visual prompt. Participants of both
simulation sessions agreed that the 6TH debriefing style was successful in
creating a non-judgmental, comfortable environment that supported open
discussion. The 6TH has the potential to be adopted as a debriefing framework,
particularly for junior faculty members without extensive debriefing training.
The 6TH is intuitive and has been marked by success in the organizational
psychology literature. Faculty development on the 6TH will be essential if this
framework is to be used as a debriefing model for educators in health care.
PMID- 29963338
TI - Single Versus Double Intramedullary Fixation of Paediatric Both Bone Forearm
Fractures: Radiological Outcomes.
AB - Introduction Both bone diaphyseal forearm fractures are common in children. If
the reduction is unstable, intramedullary fixation using elastic intramedullary
nails (EIN) is an option. Intramedullary fixation may be either of single (S-EIN)
or both (double) bones (D-EIN). Some reports have shown poorer outcomes with S
EIN. Our aim was to critically analyse the radiological features of EIN cases,
comparing results for single and both bone fixation. Method Retrospective review
(two years: November 2014-November 2016) of EIN forearm procedures. Radiological
reduction of the radius/ ulna (AP/lateral) was measured on theatre fluoroscopy
and six week radiographs. The results were categorised by angulation: (i) <10
degrees , (ii) 10-20 degrees , and (iii) >20 degrees . Results Of 36 patients (19
boys, 17 girls), 13 had S-EIN (mean age 9.6 years, range 7-14) and 23 had D-EIN
(mean age 10 years, range 7-14). In the S-EIN group, two and 11 had the ulna and
radius fixed, respectively. Intraoperatively, of the 13 S-EIN patients, nine had
<10 degrees angulation of the radius or ulna, two had 10-20 degrees and two had
>20 degrees . All 23 D-EIN patients had intraoperative radiology showing <10
degrees angulation of both bones and maintenance of reduction of <10 degrees
angulation at six weeks post surgery. However, some S-EIN patients had increased
deformation: at six weeks, four patients had 10-20 degrees and three patients
>20 degrees . No patient in either group had revisional treatment. Time in cast
postoperatively was similar in both groups: S-EIN, 6.15 weeks (4-12) and D-EIN,
5.5 weeks (3-8). Operative time was 64 mins (43-82) and 76 mins (45-86) in S-EIN
and D-EIN groups, respectively. No other complications were recorded. Conclusion
Though there may be particular reasons for selecting single bone fixation, this
series shows a propensity to increased angulation of fractures fixed by S-EIN
(7/13 in this group). We advise caution in the use of single bone fixation for
both bone forearm fractures.
PMID- 29963339
TI - Hemophagocytic Lymphohistiocytosis: A Case Series.
AB - Hemophagocytic lymphohistiocytosis (HLH) has been recognized as an inflammatory
endpoint for a variety of conditions including autoimmune diseases, malignancies
and infections. It can be further classified as primary and secondary HLH.
Primary HLH is also known as familial HLH. It usually presents in childhood and
can be associated with gene mutations. Secondary HLH is also known as acquired
HLH and usually presents in adulthood. In comparison to children, it is difficult
to diagnose adults with HLH since it occurs with a variety of different diseases
and most of the literature on HLH is derived from a pediatric population. In this
case series, we report two cases of HLH that illustrate the difficulty of making
this diagnosis and a brief review of the literature on its pathophysiology,
clinical presentation, diagnosis, and a subsequent therapeutic approach.
PMID- 29963340
TI - Career and Leadership Education in Anesthesia Residency Training.
AB - Being a well-rounded physician requires competencies that extend beyond
traditional medical training. This study explores one residency program's attempt
to address the need to foster career management and leadership skills. A year
long didactic program was initiated to tackle both career management and
leadership development. At the conclusion of the program, a survey revealed an
increase in perceived competency in the domains taught. There was also a
measurable increase in the amount of scholarly and quality improvement projects
done in the department where the program was implemented. To support and develop
physician competencies, healthcare organizations may derive immense benefit from
a program that fosters both career management and leadership skills.
PMID- 29963341
TI - Isavuconazole: A Promising Salvage Therapy for Invasive Mucormycosis.
AB - A patient with invasive mucormycosis whose disease progresses despite optimal
treatment including surgical debridement, intravenous (IV) amphotericin B, and
control of the predisposing factors can be clinically challenging. We report a
case of a 67-year-old Caucasian man with invasive mucormycosis that did not
respond to first-line treatment. He was subsequently started on isavuconazole in
addition to amphotericin B. The patient's disease progression stopped; he then
received IV amphotericin B for 50 days and isavuconazole for four months.
Repeated magnetic resonance imaging (MRI) of the orbit and face nine months
later, while off the antifungal medications, showed stable disease. This outcome
is promising for patients with invasive mucormycosis who are either intolerant to
amphotericin B or do not respond favorably to it.
PMID- 29963342
TI - Cone Beam Computed Tomography Image Quality Improvement Using a Deep
Convolutional Neural Network.
AB - Introduction Cone beam computed tomography (CBCT) plays an important role in
image-guided radiation therapy (IGRT), while having disadvantages of severe
shading artifact caused by the reconstruction using scatter contaminated and
truncated projections. The purpose of this study is to develop a deep
convolutional neural network (DCNN) method for improving CBCT image quality.
Methods CBCT and planning computed tomography (pCT) image pairs from 20 prostate
cancer patients were selected. Subsequently, each pCT volume was pre-aligned to
the corresponding CBCT volume by image registration, thereby leading to
registered pCT data (pCTr). Next, a 39-layer DCNN model was trained to learn a
direct mapping from the CBCT to the corresponding pCTr images. The trained model
was applied to a new CBCT data set to obtain improved CBCT (i-CBCT) images. The
resulting i-CBCT images were compared to pCTr using the spatial non-uniformity
(SNU), the peak-signal-to-noise ratio (PSNR) and the structural similarity index
measure (SSIM). Results The image quality of the i-CBCT has shown a substantial
improvement on spatial uniformity compared to that of the original CBCT, and a
significant improvement on the PSNR and the SSIM compared to that of the original
CBCT and the enhanced CBCT by the existing pCT-based correction method.
Conclusion We have developed a DCNN method for improving CBCT image quality. The
proposed method may be directly applicable to CBCT images acquired by any
commercial CBCT scanner.
PMID- 29963343
TI - Cardiogenic Shock: A Rare Complication of Influenza.
AB - We have presented a case of 41-year-old male who presented to the hospital with
worsening shortness of breath, fatigue and flu-like symptoms. On admission to
hospital, the patient was in severe cardiogenic shock secondary to acute
perimyocarditis. He was admitted to the cardiac intensive care unit for close
monitoring and aggressive hemodynamic support. Influenza B antigen was detected
in nasopharyngeal aspirate and the patient was started on oseltamivir. The
patient's cardiac function improved significantly in few days and he was
discharged home in stable condition with normal ejection fraction.
PMID- 29963344
TI - Ethical Considerations in Fertility Preservation for Transgender Youth: A Case
Illustration.
AB - Increasing numbers of transgender adolescents are presenting for transition
related medical care, including gender-affirming estrogen and testosterone. The
decision to transition with hormones has long-term implications, including
possible irreversible impairment of future reproductive functioning. The
commentary by Hudson, Nahata, Dietz, and Quinn (2017) outlines the importance of
fertility counseling for transgender adolescents and young adults as ethical,
interdisciplinary practice. Key considerations raised include implementing shared
decision-making strategies that account for youths' maturity and individual
decisional capacity, evaluating co-occurring psychiatric conditions that could
interfere with future-oriented decision-making, and considering benefits and
harms of fertility preservation (FP) in the context of a youth's values,
identity, and comfort. This report includes two case illustrations of
transmasculine youth which highlight how ethical considerations emerge in
clinical practice and underscore the nuance and complexity of fertility-related
decision-making among transgender adolescents.
PMID- 29963345
TI - Chemical and Dynamical Impacts of Stratospheric Sudden Warmings on Arctic Ozone
Variability.
AB - We use the Global Modeling Initiative (GMI) chemistry and transport model with
Modern-Era Retrospective Analysis for Research and Applications (MERRA)
meteorological fields to quantify heterogeneous chemical ozone loss in Arctic
winters 2005-2015. Comparisons to Aura Microwave Limb Sounder N2O and O3
observations show the GMI simulation credibly represents the transport processes
and net heterogeneous chemical loss necessary to simulate Arctic ozone. We find
that the maximum seasonal ozone depletion varies linearly with the number of cold
days and with wave driving (eddy heat flux) calculated from MERRA fields. We use
this relationship and MERRA temperatures to estimate seasonal ozone loss from
1993-2004 when inorganic chlorine levels were in the same range as during the
Aura period. Using these loss estimates and the observed March mean 63-90 degrees
N column O3, we quantify the sensitivity of the ozone dynamical resupply to wave
driving, separating it from the sensitivity of ozone depletion to wave driving.
The results show that about 2/3 of the deviation of the observed March Arctic O3
from an assumed climatological mean is due to variations in O3 resupply and 1/3
is due to depletion. Winters with a stratospheric sudden warming (SSW) before mid
February have about 1/3 the depletion of winters without one and export less
depletion to the midlatitudes. However, a larger effect on the spring midlatitude
ozone comes from dynamical differences between warm and cold Arctic winters,
which can mask or add to the impact of exported depletion.
PMID- 29963346
TI - AERONET-based nonspherical dust optical models and effects on the VIIRS Deep
Blue/SOAR over-water aerosol product.
AB - Aerosol Robotic Network (AERONET)-based nonspherical dust optical models are
developed and applied to the Satellite Ocean Aerosol Retrieval (SOAR) algorithm
as part of the Version 1 Visible Infrared Imaging Radiometer Suite (VIIRS) NASA
'Deep Blue' aerosol data product suite. The optical models are created using
Version 2 AERONET inversion data at six distinct sites influenced frequently by
dust aerosols from different source regions. The same spheroid shape distribution
as used in the AERONET inversion algorithm is assumed to account for the
nonspherical characteristics of mineral dust, which ensures the consistency
between the bulk scattering properties of the developed optical models with the
AERONET-retrieved microphysical and optical properties. For the Version 1 SOAR
aerosol product, the dust optical models representative for Capo Verde site are
used, considering the strong influence of Saharan dust over the global ocean in
terms of amount and spatial coverage. Comparisons of the VIIRS-retrieved aerosol
optical properties against AERONET direct-Sun observations at three
island/coastal sites suggest that the use of nonspherical dust optical models
significantly improves the retrievals of aerosol optical depth (AOD) and Angstrom
exponent by mitigating the well-known artifact of scattering angle dependence of
the variables observed when incorrectly assuming spherical dust. The resulting
removal of these artifacts results in a more natural spatial pattern of AOD along
the transport path of Saharan dust to the Atlantic Ocean; i.e., AOD decreases
with increasing distance transported, whereas the spherical assumption leads to a
strong wave pattern due to the spurious scattering angle dependence of AOD.
PMID- 29963347
TI - Effects of polystyrene nanoparticles on the microbiota and functional diversity
of enzymes in soil.
AB - Background: The increasing production of nanoplastics and the fragmentation of
microplastics into smaller particles suggest a plausible yet unclear hazard in
the natural environment, such as soil. We investigated the short-term effects (28
days) of polystyrene nanoparticles (PS-NPs) on the activity and biomass of soil
microbiota, and the functional diversity of soil enzymes at environmental
relevant low levels in an incubation experiment. Results: Our results showed a
significant decrease in microbial biomass in treatments of 100 and 1000 ng PS-NP
g-1 DM throughout the incubation period. Dehydrogenase activity and activities of
enzymes involved in N-(leucine-aminopeptidase), P-(alkaline-phosphatase), and C
(beta-glucosidase and cellobiohydrolase) cycles in the soil were significantly
reduced at day 28 suggesting a broad and detrimental impact of PS-NPs on soil
microbiota and enzymes. Leucine-aminopeptidase and alkaline-phosphatase
activities tended to decrease consistently, while beta-glucosidase and
cellobiohydrolase activities increased at high concentrations (e.g., PS-NP-1000)
in the beginning of the incubation period, e.g., at day 1. On the other hand,
basal respiration and metabolic quotient increased with increasing PS-NP
application rate throughout the incubation period possibly due to increased cell
death that caused substrate-induced respiration (cryptic growth). Conclusions: We
herewith demonstrated for the first time the potential antimicrobial activity of
PS-NPs in soil, and this may serve as an important resource in environmental risk
assessment of PS-NPs in the soil environment.
PMID- 29963348
TI - Institute of hydraulic engineering and water resources management (RWTH Aachen
University): an overview of research focus and training.
AB - Water is an essential element and highly valuable resource in life. Between the
priorities of environment, people and economy, it is of increasing importance to
fully understand the fundamental force of water to be capable of handling
waterborne events-such as flooding-manage and ensure water quality and
availability, and utilize hydraulic energy. The Institute of Hydraulic
Engineering and Water Resources Management (IWW) at RWTH Aachen University has a
long research tradition in this field. Going back to the founding year of the
university in 1870, the chair is based on the work of civil engineer Otto Intze,
who is best known for his pioneering contributions in construction of dams and
elevated water tanks. Ever since then, the institute has broadened its research
spectrum and is today focusing on flood protection structures, hydraulic
engineering design, integrated coastal zone management, morphodynamics and
ethohydraulics. In a comprehensive approach, physical model experiments are
combined with field measurements and numerical simulations to investigate a wide
range of projects. With its annually organized International Symposium on
Hydraulic Engineering (IWASA), the institute also offers information to a wide
audience on highly topical aspects in the field of water engineering works and
water management, while at the same time bridging the gap between science and
industry. The institute is part of the "Project House Water", a research network
at RWTH Aachen University that was established within the framework of the German
excellence initiative. Here, scientific competencies from the fields of
ecotoxicology, process engineering, geography, sociology, economy and hydraulic
engineering are focussed to allow for an interdisciplinary, holistic assessment
of flooding events and their impacts.
PMID- 29963349
TI - Variants in MEF2A gene in relation with coronary artery disease in Saudi
population.
AB - This study investigated the association of variants in myocyte enhancer factor 2A
(MEF2A) gene with coronary artery disease (CAD) via case control study on Saudi
population. Several studies have indicated a high expression of MEF2A in the
human coronary endothelium. The entire (exon 11 putative susceptibility exon) of
MEF2A gene was sequenced using direct DNA sequencing method in 120 sporadic
patients and 100 controls. Total number of variants were identified and crude
odds ratio (OR) with 95% confidence interval (CI) was calculated. In total, three
variants were identified, namely, CAG repeats, AGC deletion, and SNP rs: 325400.
No significant link was observed between the common (CAG) n polymorphism, AGC
deletion, and CAD risk as reported in other populations, but interestingly,
rs325400 (G1323T) in Saudis was found to be associated with the CAD with odds
ratio 2.0102 (CI = 1.3405-3.0146) and significance of p = 0.00048. None of Saudi
subjects (normal as well as diseased) showed 21-bp deletion as reported
previously for other populations. In addition, genotype TT of rs325400 is
associated with significantly higher levels of LDL-C and lower level of HDL-C.
Among the quantitative parameters, lower HDL-C and higher LDL-C was found to be
associated with disease. We report that MEF2A gene based on SNP rs325400 (G1323T)
can be considered as a susceptibility factor for CAD and presence of T allele
makes Saudis at more risk to CAD, while other variants detected in this gene do
not have any association in Saudi population.
PMID- 29963350
TI - Assessment and optimization of xylanase production using co-cultures of Bacillus
subtilis and Kluyveromyces marxianus.
AB - Co-cultures of Bacillus subtilis and Kluyveromyces marxianus were investigated in
submerged fermentation for xylanase production at shake-flask scale. Xylanase
production markedly increased when arabinose, xylose, or hazelnut shells were
used as the single carbon source. Maximal xylanase of 49.5 IU/mL was achieved
with 4% B. subtilis, 4% K. marxianus, 40% solid load of hazelnut shells, and pH
7.0. Overall, xylanase was enhanced by 4.4-fold compared to initial un-optimized
monoculture production and 2.8-fold compared to initial un-optimized co-cultured
production, after optimization by response surface method.
PMID- 29963351
TI - Complete genome sequence of Bacillus sp. HBCD-sjtu, an efficient HBCD-degrading
bacterium.
AB - Environmental pollution caused by the release of industrial chemicals is
currently one of the most important environmental harms. Manufacturing chemicals
can be biodegraded, and valuable intermediates can be used as pharmacophores in
drug targeting and have several other useful purposes. Hexabromocyclododecane
(HBCD), a non-aromatic brominated flame retardant, is a toxic compound that
consists of a cycloaliphatic ring of 12 carbon atoms to which six bromine atoms
are attached. It is formed by bromination of cis-trans-trans-1,5,9
cyclododecatriene, but its use is now restricted in several countries, because it
is an environmental pollutant. Little is known about whether bacteria can degrade
HBCD. A bacterial strain that degrades HBCD was recently isolated using
enrichment culture techniques. Based on morphological, biochemical and
phylogenetic analysis this isolate was categorized as Bacillus cereus and named
strain HBCD-sjtu. Maximum growth and HBCD-degrading activity were observed when
this strain was grown at 30 degrees C, pH 7.0 and 200 RPM in mineral salt medium
containing 0.5 mm HBCD. The genome of strain HBCD-sjtu, which consists of only
one circular chromosome, was sequenced. This whole genome sequence will be
crucial for illuminating the molecular mechanisms of HBCD degradation.
PMID- 29963352
TI - Production of a highly concentrated probiotic culture of Lactococcus lactis CECT
539 containing high amounts of nisin.
AB - In this study, probiotic biomass and nisin productions by Lactococcus lactis CECT
539 were followed in two realkalized fed-batch cultures in diluted whey (DW)
supplemented with KH2PO4 up to a total phosphorus concentration of 0.459 g/L.
Increased biomass (5.12 g/L, 2.18 * 1010 CFU/mL) and nisin (235.23 BU/mL)
concentrations were obtained in the culture fed concentrated whey and
concentrated mussel processing waste (CMPW) medium supplemented with glucose up
to a concentration of 400 g/L (CMPW + G medium) compared with similar fed-batch
fermentations in DW medium. In the second fed-batch fermentation, the feeding
medium CMPW + G was supplemented with KH2PO4 up to a TP concentration of 3.21
g/L. With this approach, increased production of biomass (5.49 g/L, 2.33 * 1010
CFU/mL) and nisin (257.59 BU/mL) was obtained. Considering the substantial
availability of these wastes at very low prices from local dairy and mussel
processing plants in Galicia, their use as culture media could offer an
attractive alternative for a low-cost production of probiotic biomass and nisin
at a high scale.
PMID- 29963353
TI - Computational identification and evolutionary analysis of toxins in Mosquitocidal
Bacillus thuringiensis strain S2160-1.
AB - Mosquitocidal Bacillus thuringiensis (Bt) strain S2160-1 was proposed to be an
alternative to Bacillus thuringiensis subsp. israelensis (Bti). Discovering and
validating a toxic gene by experimentation was a complex and time-consuming task,
which can benefit from high-throughput sequencing analysis. In this research, we
predicted and identified toxic proteins in the strain S2160-1 based on the draft
whole genome sequence data. Through a local BLASP, 46 putative toxins were
identified in S2160-1 genome, by searching against a customized B. thuringiensis
toxin proteins database containing 653 protein or peptide sequences retrieved
from public accessible resources and PCR/clone results in our laboratory (e value
= 1e - 5). These putative toxins consist of 42 to 1216 amino acids. The molecular
weights are ranged from 4.86 to 137.28 kDa. The isoelectric point of these
candidate toxins varied from 4.3 to 10.06, and 16 out of which had a pH greater
than 7.0. The analysis of tertiary structure and PFAM domain showed that 12
potential plasmid toxins may share higher similarity (9/12 QMEAN4 score > 0.3)
with known Bt toxins. In addition, functional annotation indicated that these 12
potential toxins were involved in "sporulation resulting in formation of a
cellular spore" and "toxin activity". Moreover, multiple alignment and
phylogenetic analysis were carried out to elucidate the evolutionary relationship
among 101 known crystal or toxin proteins from public database and them with MEGA
6.0. It indicated that PS2160P2_1 and PS2160P2_153 may be potential Cry4-like
toxins in Bt S2160-1. This research may lay the foundation for future functional
analysis of Bt S2160-1 toxin proteins to reveal their biological roles.
PMID- 29963355
TI - Characterization of a 16SrII subgroup D phytoplasma strain associated with
Calendula officinalis phyllody in Iran.
AB - Calendula officinalis plants with phyllody symptoms (CaoP) were observed in Yazd
and Ashkezar (Yazd province, Iran) during 2013-2016. Twenty-one symptomatic and
four asymptomatic plants were transferred individually to the greenhouse and
potted for the biological and molecular characterization of associated
phytoplasma. The dodder transmission from symptomatic potted marigold plants,
induced virescence, phyllody and witches' broom symptoms in periwinkle. Total
DNAs extracted from symptomatic and symptomless plants and dodder-inoculated
periwinkles were subjected to nested PCR assay using primer pairs amplifying
phytoplasma ribosomal DNA. Expected PCR amplification was detected in all CaoP
plant and dodder-inoculated periwinkle samples. RFLP analysis of the amplicons
obtained in direct PCR with P1/P7 primers using RsaI, AluI, MseI, HinfI and
HaeIII restriction enzymes showed profiles identical to each other and related to
phytoplasmas in all the 21 positive samples. R16mF2/R16mR2 amplicons from six
CaoP plant samples were sequenced where consensus sequences had 100% of identity
among each other. R16F2n/R16R2-trimmed sequences (1248 bp) of representative
samples from Yazd and Ashkezar were deposited in GenBank under accession numbers
KU297202 and MH065715, respectively. BLAST search and phylogenetic analysis
showed that the CaoP phytoplasma had 99% homology and clusters with phytoplasmas
in group 16SrII. Computer-simulated analysis using iPhyClassifier suggests that
the CaoP RFLP 16S rRNA gene pattern was identical to 16SrII-D phytoplasmas
subgroup. Phytoplasma strains (16SrII-D) were reported as alfalfa witches' broom
disease agent previously in the same geographic areas, and it is possible that
alfalfa plays a role in the epidemiology of CaoP disease or vice-versa.
PMID- 29963354
TI - Optimization of fed-batch fermentation and direct spray drying in the preparation
of microbial inoculant of acetochlor-degrading strain Sphingomonas sp. DC-6.
AB - Microbial inoculant preparation is a prerequisite for its application in large
scale bioremediation. In the present study, Sphingomonas sp. DC-6, an efficient
acetochlor-degrading strain, was used to investigate the process of preparing the
inoculant. Optimization of submerged fermentation (SmF) by response surface
methodology (RSM) resulted in a first 22% increase in biomass of liquid
inoculant. Then, a biomass increase of 2.18 times with 14.58% shortened
incubation period was further obtained in optimized medium using a 7.5-l
bioreactor. However, less than 0.4% viable cells in liquid inoculant survived
after 180-days storage. Thus, optimized spray drying conditions were subsequently
employed for the production of high viability powder (2.11 * 1012 cfu g- 1
powder) without additive and its survival ratio (SR) after 180-days storage was
still maintained at 90.5%. Both the 180-days stored powder and the original
powder showed the same degradation performance, being able to completely degrade
200 mg l- 1 acetochlor within 48 h. This study demonstrated that strain DC-6 was
suitable for industrial production of bacteria powder and provided a potential
approach for the preparation of pesticide-degrading microbial inoculant.
PMID- 29963356
TI - Xanthan gum production from acid hydrolyzed broomcorn stem as a sole carbon
source by Xanthomonas campestris.
AB - Xanthan gum is an exo-polysaccharide industrially produced by fermentation using
simple sugars. In this study, broomcorn stem was introduced as a low-cost- and
widely available carbon source for xanthan gum fermentation. Broomcorn stem was
hydrolyzed using sulphuric acid to liberate reducing sugar which was then used as
a carbon source for biosynthesis of xanthan gum by Xanthomonas campesteris.
Effects of hydrolysis time (15, 30, 45 and 60 min), sulphuric acid concentration
(2, 4, 6 and 8% v/v) and solid loading (3, 4, 5 and 6% w/v) on the yield of
reducing sugar and consequent xanthan production were investigated. Maximum
reducing sugar yield (55.2%) and xanthan concentration (8.9 g/L) were obtained
from hydrolysis of 4% (w/v) broomcorn stem with 6% (v/v) sulphuric acid for 45
min. The fermentation product was identified and confirmed as xanthan gum using
Fourier transform infrared spectroscopy analysis. Thermogrvimetric analysis
showed that thermal stability of synthesized xanthan gum was similar to those
reported in previous studies. The molecular weight of the produced xanthan (2.23
* 106 g/mol) was determined from the intrinsic viscosity. The pyruvate and acetyl
contents in xanthan gum were 4.21 and 5.04%, respectively. The chemical
composition results indicated that this biopolymer contained glucose, mannose and
glucoronic acid with molecular ratio of 1.8:1.5:1.0. The kinetics of batch
fermentation was also investigated. The kinetic parameters of the model were
determined by fermentation results and evaluated. The results of this study are
noteworthy for the sustainable xanthan gum production from low-value agricultural
waste.
PMID- 29963357
TI - Molecular characterization of carbapenemases of clinical Acinetobacter baumannii
calcoaceticus complex isolates from a University Hospital in Tunisia.
AB - The aim of this study was to identify the carbapenemases from clinical carbapenem
resistant Acinetobacter baumannii-calcoaceticus complex (CRABC) isolates and to
assess their potential dissemination by conjugation and natural transformation.
CRABC (n = 101) were collected consecutively from inpatients of the University
Hospital of Monastir, Tunisia, from 2013 to 2016. Antimicrobial susceptibility
was determined by the disk diffusion method and E-test. Carbapenemase-encoding
genes were screened by PCR. Genotyping was performed by Pasteur MLST scheme.
Isolates were resistant to all beta-lactams, fluoroquinolones and aminoglycosides
while 80 and 90% were susceptible to tigecycline and colistin, respectively.
Resistance and intermediate resistance to imipenem were 87 and 13%, respectively.
The genes blaOXA-24-like, blaOXA-58-like, blaOXA-143-like, blaOXA-48-like,
blaVIM, blaIMP, and blaKPC were not found. The blaOXA-51-like and blaOXA-23-like
genes were present in 100 and 82.17% isolates, respectively. One isolate (< 1%)
carried blaNDM-1 and blaOXA-51-like and belonged to Sequence Type 85 (ST85).
Absence of transconjugants suggests a chromosomal location of NDM-1 determinant.
The blaNDM-1 gene was inserted in a truncated form of Tn125, which may explain
the absence of blaNDM-1 carrier-transformants. To our knowledge, this is the
first report of the finding of NDM-positive A. baumannii in Tunisian territory.
The study shows that despite the low prevalence and potential spread of NDM-1
enzyme among CRABC, continuous regional antimicrobial resistance surveillance and
improved infection control measures are required in Tunisia to prevent further
dissemination.
PMID- 29963358
TI - Laccase-mediator system produced by Trametes hirsuta Bm-2 on lignocellulosic
substrate improves dye decolorization.
AB - Lignin is a source for obtaining natural phenols with high commercial value that
can act as redox mediators enhancing effects in dye decolorization. In this study
Trametes hirsuta Bm-2 was grown on wheat bran to produce laccases and phenol
extracts (PE). Ultrafiltered phenols obtained at different times were evaluated
in their potential as redox mediators of laccase activity and indigo carmin
decolorization. Laccase activity (L) on ABTS increased up to 12.4 times with
L/PE72 compared with laccase alone and L/PE48 showed the highest level of dye
decolorization (97%) compared with laccase (12%). The chromatographic analysis by
HPLC showed variation in the profile and concentration of phenols at different
times of culture. Stability of the laccase mediator system (LMs) in dye
decolorization was maintained over 3 months. Our results suggest the use of
natural mediators as a strategy for improving efficiency in dye biodegradation by
laccase-producing fungi.
PMID- 29963359
TI - Development of transgenic broccoli with cryIAa gene for resistance against
diamondback moth (Plutella xylostella).
AB - Transgenic broccoli (Brassica oleracea L. var. italica) cv. 'Solan Green Head'
has been developed by using Agrobacterium tumefaciens strain harboring cryIAa
gene for resistance against diamondback moth (Plutella xylostella). By combining
the best treatments of 72 h pre-culturing and 48 h co-cultivation time period, a
transformation frequency of 4.92 and 13.83% was obtained from cotyledon and
hypocotyl explants, respectively. Supplementing the co-cultivation medium with
acetosyringone in a concentration of 100 uM enhanced the transformation frequency
to 17.92 and 32.11% in cotyledon and hypocotyl explants, respectively. The
transgene (cryIAa) integration was confirmed by polymerase chain reaction using
gene-specific primers and Southern blot analysis using digoxigenin
nonradiolabelled DNA probe. Gene expression in the PCR-positive transgenic events
had been confirmed by reverse transcriptase-PCR and quantitative real time-PCR.
Insect bioassay proved the effectiveness of the transgene against infestation by
diamondback moth (Plutella xylostella) larvae. To the best of our knowledge, this
is the first report of optimization of a highly efficient transformation system
and transgenic development in broccoli using cry1Aa gene for insect resistance.
PMID- 29963361
TI - Characterization of bacterial community structure during in-vessel composting of
agricultural waste by 16S rRNA sequencing.
AB - Bacterial diversity during in-vessel (rotary drum) composting of agricultural
waste was characterized using NGS-based 16S rRNA sequencing for microbial
identification. The activity of the bacteria was observed to vary with the
composting materials and degradation pattern. Taxonomic hits distribution at
domain level revealed that 89.5% sequences belonged to bacteria, 9% to eukaryota
followed by 1.4% archaea during drum composting. The lowest common ancestor (LCA)
classification plot showed the high abundance of the phylum proteobacteria
followed by actinobacteria in compost sample. Taxonomic hit distribution at
family level showed that compost sample was enriched with Thermomonosporaceae.
Thermomonospora curvata is an aerobic, cellulolytic, thermophilic Gram-positive
bacterium which produces a number of industrially important compounds, i.e.,
cellulase, alpha-amylase, and polygalacturonate lyase. Thermomonospora family of
bacteria play a major role in organic matter degradation during composting.
Hence, in the present study species such as Actinomadura vinacea, Thermomonospora
curvata, Actinoallomurus spadix, Actinomadura rubrobrunea. T. curvata were
identified from the compost mixture, which can utilize many organic compounds
such as cellulose starch, xylose or pectin. The other biggest group in compost
sample was Actinobacteria with Thermoleophilum album as the most abundant species
followed by Collinsella aerofaciens. The compost was stabilized with higher
volatile solids reduction, lower OUR (4.49 mg/g VS/day) and CO2 (2.28 mg/g
VS/day) values at the end of 20 days. The final compost was observed with 2.31%
of TKN and 4.3% of phosphorus. Finally the results indicate that degradation of
agricultural waste using drum composter was dominated by Bacilli, gamma, beta
proteobacteria, and actinobacteria.
PMID- 29963360
TI - Photo-fermentation of purple sweet potato (Ipomoea batatas L.) using probiotic
bacteria and LED lights to yield functionalized bioactive compounds.
AB - The purpose of this study was to examine if fermentation of purple sweet potato
(Ipomoea batatas L.) powder (PSP) by Lactobacillus brevis under green, red, blue,
white light-emitting diode (LED) illumination or sunlight might yield
functionalized products with good antibacterial, antioxidant activity, and/or
cytotoxic activity. The Purple sweet potato (PSP) powder fermented with probiotic
bacteria L. brevis under white LED light (1.9 +/- 1.80/1.6 +/- 0.52), blue LED
light (1.4 +/- 1.32/1.8 +/- 0.83), or sunlight (1.2 +/- 1.26/1.5 +/- 1.83) for
Propionibacterium acne and Staphylococcus epidermidis displayed good to moderate
antibacterial activity based on minimum inhibitory concentration (MIC) red, blue,
white LED lights and sunlight (80 ug/mL) for P. acne and S. epidermidis, minimum
bactericidal concentration red, blue LED lights and sunlight shows (46/48, 61/70,
50/48 ug/mL) for P. acne and S. epidermidis. Antioxidant activity for dark,
white, blue and green LED lights for ABTS and white, blue and green Led for DPPH
assay resulted in lower activity. Fourier transform infrared spectroscopy was
performed to determine the functional groups in the non-fermented (control) and
fermented products of PSP powders obtained using different light sources.
Sunlight, white, and blue LED light-fermented extracts contained alcohol, acid,
and phenol groups, as well as aliphatic amines. The results of this study clearly
indicate that fermentation of purple sweet potato with probiotic bacteria under
various LED light sources can yield compounds that can be used in cosmetic and
value-added food products.
PMID- 29963362
TI - Impulsivity and Alcohol Involvement: Multiple, Distinct Constructs and Processes.
AB - Of all the personality traits associated with problematic alcohol involvement,
traits related to impulsivity appear to show the most robust relations to alcohol
use and alcohol-related problems. This article reviews both seminal articles that
focus on broadband measures of impulsivity and newer research linking more
specific impulsivity-related traits to the development and course of problematic
alcohol involvement, with a specific focus on self-report measures of impulsivity
related traits. Specifically, empirical support for different theoretical models
that account for the overlap between impulsivity-related traits and problematic
alcohol involvement is discussed, including current limitations of existing
research. Recent studies suggest that specific impulsivity constructs relate to
distinct aspects of alcohol-related behavior. Further, there is emerging evidence
that problematic alcohol use and impulsivity-related traits are dynamically
related, such that changes in these constructs appear to correlate during
specific developmental periods. We close by discussing potential research
directions that may provide increased clarity in understanding the impulsivity
alcohol relation.
PMID- 29963364
TI - Brief Interventions in Primary Care: an Evidence Overview of Practitioner and
Digital Intervention Programmes.
AB - Purpose of the Review: Excessive drinking is a major public health problem that
adversely affects all parts of the population. Previous systematic reviews and
meta-analyses have reported that brief interventions delivered in primary care
are effective at reducing alcohol consumption, albeit with small effect sizes
that have decreased over time. This review summarises the updated evidence base
on practitioner and digitally delivered brief interventions. Recent Findings:
Using Cochrane methodology, 69 primary care brief intervention trials (33,642
participants) and 57 digital intervention trials (34,390 participants) were
identified. Meta-analyses showed both approaches significantly reduced
consumption compared to controls. Five trials (390 participants) compared
practitioner-delivered and digital interventions directly with no evidence of
difference in outcomes at follow-up. Summary: Brief interventions have the
potential to impact at both individual and population levels. Future research
should focus on optimising components and delivery mechanisms, and on alcohol
related harms. Digital interventions may overcome some of the implementation
barriers faced by practitioner-delivered interventions.
PMID- 29963363
TI - Learned Overeating: Applying Principles of Pavlovian Conditioning to Explain and
Treat Overeating.
AB - Purpose of Review: This review provides an overview of recent findings relating
to the role of Pavlovian conditioning in food cue reactivity, including its
application to overeating and weight loss interventions. Recent Findings: Both in
the laboratory and in real life, cue-elicited appetitive reactivity (e.g., eating
desires) can be easily learned, but (long-term) extinction is more difficult. New
findings suggest impaired appetitive learning in obesity, which might be causally
related to overeating. The clinical analogue of extinction-cue exposure therapy
effectively reduces cue-elicited cravings and overeating. While its working
mechanisms are still unclear, some studies suggest that reducing overeating
expectancies is important. Summary: Pavlovian learning theory provides a still
undervalued theoretical framework of how cravings and overeating can be learned
and how they might be effectively tackled. Future studies should aim to elucidate
inter-individual differences in Pavlovian conditioning, study ways to strengthen
(long-term) extinction, and investigate the working mechanisms of cue exposure
therapy.
PMID- 29963365
TI - Using Informant and Performance Screening Methods to Detect Mild Cognitive
Impairment and Dementia.
AB - Purpose of Review: Dementia detection in the community is challenging. The
purpose of this paper is to review methods of dementia screening and provide a
useable algorithm for screening for dementia a variety of clinical settings.
Recent Findings: In recent years, a number of brief performance and informant
based assessments have been developed and validated in research, clinical, and
community samples. These assessments are now complemented by patient self-reports
that afford the ability to detect subjective cognitive impairment. Summary: An
optimal approach to dementia screening is to combine performance, informant, and
self-reports, many of which can be completed in the waiting room or by non
physician staff prior to the start of the office visit. This diverse information
may help inform the provider as to the presence or absence of a cognitive
disorder, assist in staging the extent of the disorder, and help to develop a
differential diagnosis and management plan.
PMID- 29963366
TI - Have we increased our efforts to identify strategies which encourage colorectal
cancer screening in primary care patients? A review of research outputs over
time.
AB - Globally, colorectal cancer (CRC) screening rates remain suboptimal. Primary care
practitioners are supported by clinical practice guidelines which recommend they
provide routine CRC screening advice. Published research can provide evidence to
improve CRC screening in primary care, however this is dependent on the type and
quality of evidence being produced. This review aimed to provide a snapshot of
trends in the type and design quality of research reporting CRC screening among
primary care patients across three time points: 1993-1995, 2003-2005 and 2013
2015. Four databases were searched using MeSH headings and keywords. Publications
in peer-reviewed journals which reported primary data on CRC screening uptake
among primary care patients were eligible for inclusion. Studies meeting
eligibility criteria were coded as observational or intervention. Intervention
studies were further coded to indicate whether or not they met Effective Practice
and Organisation of Care (EPOC) study design criteria. A total of 102
publications were included. Of these, 65 reported intervention studies and 37
reported observational studies. The proportion of each study type did not change
significantly over time. The majority of intervention studies met EPOC design
criteria at each time point. The majority of research in this field has focused
on testing strategies to increase CRC screening in primary care patients, as
compared to research describing rates of CRC screening in this population.
Further research is needed to determine which effective interventions are most
likely to be adopted into primary care.
PMID- 29963368
TI - Large bladder stone as a complication of AUS insertion and bladder augmentation.
PMID- 29963369
TI - Ovarian type epithelial tumor of the tunica vaginalis with abdominal metastasis.
PMID- 29963367
TI - Does intensified chemotherapy increase survival outcomes of osteosarcoma
patients? A meta-analysis.
AB - Study Design: Meta-analysis. Background: Although some new insights have been
offered for clinical and scientific relevance, minor progress has been made in
osteosarcoma treatment after a dramatic survival improvement in the late 1980s
with the addition of chemotherapy to surgery. Intensified chemotherapy strategies
have been suggested to increase the survival rate of patients with osteosarcoma.
We performed this study to access whether intensified chemotherapy
strategiesincreased survival outcomes of osteosarcoma patients compared with
conventional chemotherapy strategies. Methods: MEDLINE/PubMed, EMBASE, BIOSIS
Previews, and Cochrane Library were searched from database set up to October2016.
Randomized controlled trials (RCTs) and comparative clinical trials (CCTs) on
intensified versus conventional chemotherapy strategies for osteosarcoma patients
met the inclusion criteria, and the methodological quality standard were
retrieved and reviewed. Data on participant characteristics, interventions,
follow-up period, and outcomes were extracted from the included studies and
analyzed by Review Manager 5.3. Results: 12 studies (8 RCTs and 4CCT) involving
4112 patients were selected. There were no significant differences between
intensified and conventional chemotherapy strategies group in 3-year event-free
survival (OR, 1.01; 95% CI, [0.74-1.37]; P = 0.97), 5-year event-free survival
(OR, 1.00; 95% CI, [0.86-1.17]; P = 0.97), and 5-year overall survival (OR, 1.04;
95% CI, [0.87-1.26]; P = 0.64), and good histologic response to preoperative
chemotherapy (OR, 1.12; 95% CI, [0.78-1.60]; P = 0.55). Pooled analysis of local
recurrence rate showed that local recurrence rate was significantly decreased in
the intensified group compared with that in the conventional group (OR, 0.60; 95%
CI, [0.42-0.85]; P = 0.004). Conclusions: Intensified chemotherapy might not be a
preferred treatment for all of the osteosarcoma patients.
PMID- 29963370
TI - Mucoid degeneration of the cruciate ligaments in osteoarthritis under primary
total knee arthroplasty.
AB - Mucoid degeneration of the anterior cruciate ligament (ACL) and posterior
cruciate ligament (PCL) with osteoarthritis is rarely reported. We experienced
two knee osteoarthritic patients who had symptomatic mucoid degeneration of their
ACL, and their PCL was also diagnosed as mucoid degeneration in histological
evaluation. Preoperative radiological evaluation could not reveal precisely
whether the degeneration had extended to the PCL. We obtained good clinical
results treating them with posterior-stabilized (PS) total knee arthroplasty
(TKA) sacrificing both ligaments. In cases of osteoarthritis with mucoid
degenerated ACL, PS TKA should be considered, sacrificing both cruciate
ligaments, because mucoid degeneration might expand both cruciate ligaments.
PMID- 29963371
TI - Evaluating different closed loop graft preparation technique for tibial
suspensory fixation in ACL reconstruction using TightRopeTM.
AB - In most anterior cruciate ligament (ACL) reconstructions, grafts are fixed to the
femoral side first followed by the tibial side. Various techniques have been
reported to achieve optimal tension on the grafts, but once the grafts are fixed
it is difficult to adjust graft tension further. To enable post fixation tension
control we have invented a new graft configuration using an adjustable loop
device (TightRopeTM, Arthrex, FL, USA) on the tibial side. In this paper,
biomechanical properties of this configuration using soft tissue were examined in
terms of graft diameter and various suture techniques (referred to as base
suture) to make a closed circle to support TightRopeTM. Two experiments were
conducted under different conditions. In each experiment, cyclic load, followed
by a pull-to-failure load, was applied to the grafts and elongation and failure
mode were recorded. (1) To evaluate the effects of diameter, 5.0 or 6.0 mm grafts
were prepared by a single locking loop stitch as the base suture (SLL5, SLL6).
(2) To evaluate different base sutures, 5.0 mm tendons were used, and grafts were
prepared using five kinds of base sutures (SLL, ZLL: zigzag locking loop, DZLL:
double zigzag locking loop, DK: double Krackow, DK w/o TR: double Krackow without
TightRopeTM). In the first experiment, tearing was observed in 2 of 6 cases in
the SLL5 test group, whereas no tearing was observed with SLL6. In the second
experiment, no tearing was observed with DZLL or DK. Elongation was smaller in
these two groups compared to the other groups. Mechanical strength decreases with
a smaller graft diameter. Biomechanical properties differed with different base
sutures and, among them, the double-zigzag-suture stitch and double Krackow
provided less elongation and higher ultimate load in this graft configuration.
PMID- 29963372
TI - Kinematic analysis of a televised medial ankle sprain.
AB - Ankle sprains are one of the most prevalent athletic injuries. Prior work has
investigated lateral ankle sprains, but research on generally more severe medial
sprains is lacking. This case report performs a kinematic analysis using novel
motion analysis methods on a non-contact medial ankle sprain. Peak eversion (50
degrees ) occurred 0.2 seconds following ground contact, maximum velocity of 426
degrees /s, while peak dorsiflexion (64 degrees ) occurred with a greater maximum
velocity (573 degrees /s). The combination of dorsiflexion at ground contact and
rapid eversion is associated with a non-contact eversion sprain. This study
provides a quantitative analysis of the eversion ankle sprain injury mechanism.
PMID- 29963373
TI - Prediction of graft length by body height in anatomic double-bundle anterior
cruciate ligament reconstruction.
AB - To investigate the intra-articular graft length and the length of the bone
tunnels after anatomic double-bundle (DB) ACL reconstruction with semitendinosus
(ST) tendon, and predict the required length of ST tendon, 178 patients who
underwent anatomic DB ACL reconstruction with ST tendon were analyzed. The length
of the intra-articular graft was measured by CT. A regression analysis was
performed to determine the correlation between the intra-articular graft length
and patient height. There was a statistically significant correlation between the
intra-articular graft length and patient height. Therefore, the required length
of ST tendon can be predicted from patient height.
PMID- 29963374
TI - Return to sport and knee functional scores after anterior cruciate ligament
reconstruction: 2 to 10 years' follow-up.
AB - Background: Anterior cruciate ligament (ACL) reconstruction is one of the most
common knee ligament reconstruction sustained by sports players. Previous studies
have revealed different rates of returning to play sports depending on study
sites, subjects, and time to follow-up; however, this subject has not been
adequately investigated in Thailand. Objectives: This study aimed to assess the
percentage of ACL reconstruction patients who successfully returned to sport
activities. Factors associated with being able to return to sport were also
determined. Materials and methods: A cross-sectional study was conducted to
assess the rates of return to sport of patients who underwent ACL reconstruction
between 2005 and 2015. All potential patients were initially contacted via letter
or mobile phone and asked to report their long-term follow-up outcomes. Collected
data from the interview, including return to sport status, performance following
ACL, and reasons for not returning to play (if applicable) were then combined
with the initial surgical findings and enrollment/follow-up cohort data for
analysis. This study was reviewed and approved by the ethics committee of
Rajavithi Hospital. Results: A total of 110 participants were recruited, with a
mean age of 35.05 +/- 9.16 years. Most of the patients were male, single, with
bachelor degree education, engaged in "other" occupations, had income up to
10,000 baht/month, were in the social security scheme (54.5%), and had no
underlying diseases (85.5%). The mean +/- SD of BMI was 25.58 +/- 4.30 kg/m2.
When classified by whether or not they returned to sports, it was found that sex,
education, income and underlying disease of those who returned to sport were
significantly different from those of subjects who did not (p < 0.05). At follow
up, 36.4% had returned to sport. The main reasons stated for not returning to
sport following ACL were fear of injury, concern about possible long-term
effects, and worry about the possibility of re-injury. Overall, total IKDC scores
of patients who returned to sport were significantly higher than those of
subjects who did not. However, some points such as ability to kneel, ride and
bend the knee were not different in the two groups. Bachelor degree education,
monthly income lower than 10,000 Thai baht and IKDC score were the factors
associated with returning to sport. Conclusions: The rates of return to sport
after ACL reconstruction were low compared to those of other reports in the
literature. Education, low income and IKDC score were predictive factors of sport
re-participation. Further studies should be carried out to assess the impact on
treatment indications and rehabilitation.
PMID- 29963375
TI - VATS and RATS lobectomy up to date: clinical and experimental evidences.
PMID- 29963376
TI - Ten-year experience with the Perceval S sutureless prosthesis: lessons learned
and future perspectives.
AB - Aortic stenosis has traditionally been addressed with surgical aortic valve
replacement (AVR). In recent years, several technologies have emerged as
alternative treatment methods for aortic valve disease. Among them, the Perceval
(LivaNova, London, UK) is a sutureless valve that has been used in clinical
practice for over 10 years. It has been implanted in over 20,000 patients
worldwide. With nearly 600 Perceval implants since 2011, the Montreal Heart
Institute has developed a worldwide expertise with this technology. In this
article, we provide an overview of the clinical data currently available in the
literature and discuss the lessons we have learned from our experience with the
Perceval prosthesis.
PMID- 29963378
TI - The state of the art of the minimally invasive thoracic surgery in Italy.
PMID- 29963377
TI - An unusual etiology of hyperparathyroidism: robotic-assisted resection of a giant
functional intrathymic parathyroid cyst.
AB - Parathyroid cysts (PCs) are relatively rare entities, with an even smaller
proportion that functionally produce parathyroid hormone (PTH). Given associated
hypercalcemia, often symptomatic, as well as potentially related osteoporosis
and/or nephrolithiasis, resection of these functional cysts is often indicated.
This case report details the management course for a patient who presented with
primary hyperparathyroidism and was ultimately found to have a functional
intrathymic PC. During initial workup, 4-dimensional computed tomography (4D-CT)
of the neck demonstrated enlarged left upper and right lower parathyroid glands;
however, the patient's hyperparathyroid state persisted even after bilateral neck
exploration and resection of these two glands. Subsequent postoperative imaging
of the mediastinum revealed a large (11 cm) thymic cyst. The patient consequently
underwent uneventful robotic-assisted thoracoscopic excision of the mediastinal
cyst. Intraoperative blood PTH levels dropped from 734 pg/mL preoperatively to 86
pg/nL 10 minutes following resection, consistent with surgical cure by the Miami
Criteria. At two months postoperatively, the patient's serum total calcium (STC)
was normal at 9.2 mg/dL. Final surgical pathology noted a 15-gram parathyroid
gland, with cystic degeneration. As the robot becomes further integrated into the
everyday practice of thoracic surgery, we believe this approach offers advantages
over conventional video-assisted thoracoscopic surgery (VATS) for mediastinal
resections. Advantages include better visualization and finer, more precise
dissection, especially important in this case, given the proximity of vital
structures and the small, but real, risk of parathyromatosis associated with
intraoperative cyst rupture.
PMID- 29963379
TI - Ultra fast track surgery: a rapid deployment aortic valve replacement through a J
ministernotomy.
AB - Aortic valve surgery has been undergone continuous development over the last
years, involving less invasive techniques and the use of new technologies to
reduce the traumatic impact of the intervention and extend the operability toward
increasingly high-risk patients. Minimally invasive aortic valve replacement
(AVR) has gradually been recognized as a less traumatic technique compared to
median sternotomy, becoming first choice approach in numerous experienced
centers. Herein we present our multidisciplinary minimally invasive approach for
AVR, involving: (I) reduced chest incision; (II) rapid deployment AVR; (III)
minimally invasive extracorporeal circulation system; and (IV) ultra fast track
(UFT) anaesthetic management.
PMID- 29963380
TI - Preface for minimally invasive surgery for lung cancer.
PMID- 29963381
TI - Thoracic endovascular aortic repair for the ascending aorta: experience and
pitfalls.
AB - Thoracic endovascular aortic repair (TEVAR) of the ascending aorta is a
developing alternative treatment strategy, which currently is specifically aimed
at patients who are too high risk for open surgery. TEVAR has been applied to
patients with a variety of pathologies of the ascending aorta including type A
dissection, intramural hematoma (IMH), penetrating ulcers, aneurysm and
pseudoaneurysm. Here we discuss the current evidence regarding the use of TEVAR
for the ascending aorta as well as the latest techniques and pitfalls of the
procedure. The challenges of this modality are considerable, and the techniques
that have been applied draw from the many facets of endovascular experience.
There is limited literature regarding the use of stent grafts in the ascending
aorta, and the pool of patients currently considered appropriate candidates for
the procedure is small. This is an evolving intervention that warrants further
study and the development of devices specifically engineered to meet the
anatomical and physiologic challenges of the ascending aorta.
PMID- 29963382
TI - Using FloSeal(r) to control digestive bleeding in the distal large bowel.
AB - We present an alternative treatment to resolve lower gastrointestinal bleeding by
the application of FloSeal, a haemostatic matrix. Fundamentally, the treatment
consists of inserting the tube containing the Sengstaken-Blakemore probe
impregnated with FloSeal into the rectum-sigma. This procedure is simple, easy to
reproduce and can be very useful to control bleeding in the last section of the
gastrointestinal tract.
PMID- 29963383
TI - Biological solutions to aortic root replacement: valve-sparing versus
bioprosthetic conduit.
AB - Composite valve graft implantation described by Bentall and De Bono is a well
documented technique of aortic root replacement used for a large spectrum of
pathologic conditions involving the aortic valve and the ascending aorta. While
mechanical valves were initially used, biological prostheses were later
introduced in order to avoid long-term anticoagulation and its related
complications. The increasing age of patients who undergo aortic root surgery,
and data supporting the use of a biological aortic valve in the younger
population, have significantly increased the need for a composite biological
valved conduit. However, parallel to the increased use of biological valve in the
context of a Bentall operation, aortic valve-sparing (AVS) operation have also
been performed in a growing number of patients. Sarsam and David described the
remodeling and the reimplantation procedures more than 25 years ago with the aim
of sparing otherwise normal aortic valves in the presence of a root aneurysm.
Important achievements in this discipline have occurred over the past decade
including development and refinement of valve preserving aortic root replacement
techniques, development of a classification system for aortic insufficiency,
surgical approaches to cusp disease with different cusp anatomy. Both procedures
can now provide excellent root reconstruction and adequate clinical results in
terms of late valve durability. The AVS technique offers several advantages over
the Bentall procedure, such as no need for oral anticoagulation and lifestyle
adjustments. AVS operations have become established alternatives to Bentall
procedures for patients with aortic root pathology. However, data comparing the
safety and durability of these approaches are lacking.
PMID- 29963385
TI - Made for each other.
PMID- 29963384
TI - 4D flow characterization of aortic blood flow after valve sparing root
reimplantation procedure.
AB - Valve-sparing aortic root replacement (VSRR) with reimplantation technique is an
effective alternative for young patients with dilated roots and preserved cusps,
which avoids the risks of lifelong anticoagulation or valve degeneration. New
grafts with anatomically-shaped sinuses have been developed in order to preserve
aortic root physiology, which could decrease complication rates and improve
durability. However, controversy remains regarding the effect of recreation of
the sinuses of Valsalva during VSRR on long-term outcomes. The novel 4D flow
technique, exploiting its unique ability to combine anatomical evaluation of the
root with fluid-dynamic assessment of aortic flow, enables integrated analysis of
the close interaction between graft design, valvular morphology and three
dimensional (3D) flow characteristics. Early experimental studies have shown how
graft shape affects the aortic root flow pattern, formation of vortexes and
helicity of downstream flow; however, the clinical significance of these findings
is yet to be clarified. Various and still unexplored knowledge can be obtained
from the qualitative and quantitative analysis of these complex datasets, that
could shed more light on which is the best among myriad surgical techniques and
grafts adopted in VSRR. The extraordinary potential 4D flow imaging opens new
boundless horizons in the perspective of an increasingly patient-tailored
surgical planning.
PMID- 29963386
TI - Uniportal, single incision VATS for the skeptics.
PMID- 29963387
TI - The evidence in a Bentall procedure with Valsalva graft: is this standard of
care?
AB - Background: Biologic valved-conduits avoids the need for anticoagulation and can
exploit the excellent hemodynamic performance of stentless valves. Incorporation
of the sinuses of Valsalva into the neoaortic root can improve the function and
longevity of stentless valves. We report our experience in performing the Bentall
procedure with a self-prefabricated composite valved-conduit and review the
published experience with the Valsalva graft. Methods: From Feb 2005 through Sep
2017, 428 patients underwent aortic root replacement utilizing a composite graft
constructed from a 27-29-mm Freestyle MS valve (Medtronic) sutured into a 28-30
mm Gelweave Valsalva prosthesis (Sulzer Vascutek, Renfrewshire, Scotland). Data
were retrospectively analyzed. Results: Mean age was 58+/-13 years, with a male
predominance (337, 79%). Additional surgical procedures included a mitral valve
repair/replacement in 10 patients (2%), coronary artery bypass graft (CABG) in
114 patients (27%), and aortic arch (hemi or total) replacement in 252 patients
(59%). Average cardiopulmonary bypass, cross-clamp, and circulatory arrest times
were 210+/-57, 180+/-44, and 29+/-15 min, respectively. Thirty-day mortality was
7% (31 patients). Mean echocardiography follow-up was 27.2+/-29.0 months (range,
1-138 months). Pressure gradients (mean, peak) across the aortic valve on latest
echocardiography were 5.59, 10.57 mmHg respectively. Freedom from >2+ aortic
insufficiency (AI) at 6 and 9 years was 96%, and 87% respectively. Freedom from
aortic valve replacement (AVR) at 6 and 9 years was 99%, and 95% respectively. To
date, 4 (1%) patients required an additional aortic valve intervention secondary
to structural valve degeneration. Conclusions: Use of the Valsalva graft combined
with the Freestyle valve for Bentall procedures is associated with favorable
results. Clinical outcomes are excellent and in longitudinal follow-up, valve
related complications are minimal.
PMID- 29963388
TI - Aortic and mitral valve repair for anterior mitral leaflet perforation caused by
severe aortic regurgitation.
AB - A 23-year-old man presented with acute onset of dyspnea on exert. Preoperative
echocardiography showed a severe regurgitation of the bicuspid aortic valve (due
to prolapse of the fused cusp) creating a jet directed through the defect in the
anterior leaflet of the mitral valve. Both valves were repaired. Endocarditis was
excluded with cultures and polymerase chain reaction (PCR). Postoperative course
was uneventful.
PMID- 29963389
TI - Endoscopic Port AccessTM left ventricle outflow tract resection and
atrioventricular valve surgery.
AB - The continuous evolution in robotic-, endoscopic- and trans-catheter cardiac
interventions resulted in innovative techniques that simultaneously address left
ventricular outflow tract obstruction (LVOTO) and concomitant atrioventricular
valve (AVV) pathology in the context of hypertrophic obstructive cardiomyopathy
(HOCM). We present our brief report of 13 consecutive HOCM patients with
concomitant AVV disease, who underwent endoscopic left ventricular septal
myomectomy (LVSM) and AVV surgery by Endoscopic Port AccessTM Surgery (EPAS)
between March 1st 2010 and October 31st 2015. Our EPAS technique in the context
of HOCM utilizes peripheral cardiopulmonary bypass, endo-aortic balloon occlusion
and a 4-cm right antero-lateral thoracic working port. Access to the LVOTO is
obtained by detaching the anterior mitral valve (MV) leaflet from the annulus.
Controlled sharp LVSM is then performed from the aortic leaflet base to the
papillary muscles. Subsequent routine AVV surgery is performed using long shafted
instruments. There were no sternotomy conversions, LVSM complications or 30-day
mortalities. The mean length of hospitalization was 17.7+/-18.1 days. Long-term
clinical and echocardiographic analysis of 645.7 patient-months (n=13, 100.0%
complete) identified two late mortalities, which were not procedure-, HOCM- or
AVV-related. All patients (n=13, 100.0%), including the late mortalities, had
significant improvement in their quality of life, a 100% long-term freedom from
re-intervention and no residual peak instantaneous LVOTO gradients more than 15
mmHg. This brief report emphasises that simultaneous LVSM and concomitant AVV
surgery by EPAS can safely be performed in experienced centres with favourable
long-term outcomes.
PMID- 29963390
TI - Bicuspid aortic valve repair in the setting of severe aortic insufficiency.
AB - Background: Bicuspid aortic valve (BAV) is a common cardiac anomaly that affects
0.5-2% of adults. Valve sparing root replacement (VSRR) in bicuspid aortopathy is
gaining popularity. We discuss the technical aspects of the procedure as well as
the mid- to long-term results of performing VSRR in the setting of a bicuspid
valve. Methods: A single institutional database identified 280 patients who
underwent VSRR from 2005-2016. Outcomes were analyzed in 60 consecutive patients
undergoing a VSRR in the setting of a BAV with aortic regurgitation (AR).
Patients were followed prospectively and had annual echocardiograms. Results: The
average age in this series was 42+/-11 years. Moderate or more AR was present in
50% of patients preoperatively. The incidence of operative death, stroke, and
renal failure was 0%. Mean follow-up was 39+/-30 months. At latest follow-up, 62%
of patients had zero AR and 87% of patients had <1+ AR. At 9 years, freedom from
>2+ AR was 97% and freedom from aortic valve repair (AVR) was 96%. Conclusions:
VSRR can be safely and effectively performed in young patients with bicuspid
valve anatomy regardless of degree of pre-operative AR. Valve function is durable
and the incidence of valve-related complications is low. VSRR is an attractive
and potentially superior option to conventional root replacement in appropriately
selected patients with bicuspid aortopathy.
PMID- 29963391
TI - Transcaval transcatheter aortic valve replacement: a visual case review.
AB - Transcatheter aortic valve replacement (TAVR) has emerged as a viable, minimally
invasive and widely adopted approach for the treatment of severe symptomatic
aortic stenosis in patients who are intermediate-risk or greater for surgical
aortic valve replacement. Numerous studies have demonstrated favorable outcomes
with TAVR in this population, particularly with transfemoral access TAVR.
Transfemoral TAVR has been shown to be safer and associated less morbidity,
shorter lengths of hospital stay and more rapid recovery as compared with
traditional thoracic alternative-access TAVR (transapical or transaortic).
Despite iterative advancements in transcatheter heart valve technology and
delivery system, there remain a portion of patients with iliofemoral arterial
vessel sizes that are too small for safe transfemoral TAVR. Paradoxically, these
patients are generally higher risk and are thus less favorable candidates for
open surgery or traditional alternative-access TAVR. With these considerations in
mind, transcaval TAVR was developed as a fully percutaneous, non-surgical
approach for aortic valve replacement in patients who are poor candidates for
traditional alternative-access TAVR. In this manuscript we describe the
principles on which transcaval TAVR was developed, the outcomes from the largest
trial completed evaluating this technique as well as describing the technique
used to perform this procedure in a case-based format.
PMID- 29963392
TI - Novel extra-thoracic VATS minimally invasive technique for management of multiple
rib fractures.
AB - We report an elderly patient with chronic obstructive pulmonary disease (COPD),
Alzheimer's disease and early dementia who presented with multiple displaced rib
fractures of left ribs 4 through 9 with flail segments of ribs 4 through 8 and an
associated traumatic pneumatocele from rib puncture of the left upper lobe. The
decision to treat this patient operatively was based on the presence of flail
chest, the patient's age, baseline co-morbidities and limited physiological
reserve. Surgical rib fixation is traditionally performed with a thoracotomy
incision and open exposure for extra-thoracic rib fixation, however, this patient
underwent chest wall stabilization using an extra-thoracic video-assisted
thoracic surgery (VATS) technique. We discuss our operative technique using
universal rib plating system, optimal retraction for exposure and use of balloon
dilation to create an accessible extra-thoracic working space. This surgical
approach provided a faster recovery to this patient's baseline with minimal use
of narcotics thereby highlighting the impact and importance of this surgical
technique for patients presenting with multiple fib fractures, especially the
elderly. We show that VATS assisted minimally invasive technique for operative
management of multiple rib fractures is a viable surgical option demonstrated by
this patient's recovery and return to function with minimal need for pain control
despite her advanced age and baseline co-morbidities.
PMID- 29963394
TI - Hybrid robotic thoracic surgery for excision of large mediastinal masses.
AB - Between April 2016 and October 2017, we retrospectively reviewed all patients
undergoing excision of large mediastinal masses using a hybrid robotic thoracic
approach at the Unit of Thoracic Surgery of Monaldi Hospital in Naples. The
inclusion criteria for this approach were: evident unilateral predominance of the
mass; absence of invasion to surrounding structures. Planned conversion to
sternotomy was necessary in one patient for tenacious adhesions between the
mediastinal goiter and the left innominate vein. In all cases the postoperative
course was uneventful. The hybrid robotic approach, adopted in our Unit, consists
of a thoracic procedure performed completely with articulated surgical
instruments under three-dimensional vision and followed by final extension of a
port-site incision to retrieve the voluminous specimen. This approach uses all
the advantages of robotic technology that enables to perform a fine dissection in
the small space of the anterior mediastinum and at the same time, through the
simple extension of a minimally invasive access, avoids the painful sequelae of
thoracotomy. In selected cases, with increased experience in robotic surgery, it
can be proposed for excision of large mediastinal masses, although a longer
follow-up period is necessary to validate our findings.
PMID- 29963393
TI - The influence of the trocar choice on post-operative acute pain after
thoracoscopy.
AB - Background: Acute post-operative pain following thoracic surgery procedures is
still an unresolved problem despite the introduction of minimally invasive
procedures such as video assisted surgery. Until now it is never investigated if
different surgical instruments could influence post-operative pain. The aim of
our study is to investigate the role of different type of trocar on post
operative pain in minimally invasive thoracic surgery. Methods: This was a
prospective randomized single center study. We identified 53 patients randomized
into three groups underwent single port thoracoscopy for malignant pleural
effusion with drainage of the fluid and talc poudrage. The three groups differ
for the trocar type, rigid, flexible and wound protector. Results: We compared
the postoperative pain between the three groups in which there was no statistical
difference. Rigid trocar seems to give a more stable level of pain during the
days, flexible trocar gains more pain in the first few hours, however the pain at
discharge decreases significantly, reaching the similar values, in all the three
groups. The association between pain at discharge and operative time or days of
drainage was analyzed by means of linear regression, no statistically significant
difference was found. Conclusions: Our study showed that different type of
trocars during video assisted thoracic surgery (VATS) produces similar level of
acute postoperative pain. In future, further randomized study with a great number
of patients enrolled needs to confirm our results.
PMID- 29963395
TI - Pattern, timing, and predictors of recurrence following pancreatectomy for
pancreatic ductal adenocarcinoma: how do they matter?
PMID- 29963396
TI - From "open" to robotic assisted thoracic surgery: why RATS and not VATS?
PMID- 29963397
TI - Aberrant subclavian: new face of an old disease.
AB - An aneurysm of an aberrant subclavian artery is un usual prevalence of anomalies
of aortic arch, with a literature reported prevalence of 2%. Timely elective
intervention is of paramount. The advancement in stenting techniques has promoted
this practice to be an alternative to conventional open surgical repair which is
associated with high rates of perioperative complications including mortality
outcomes. However, new faces of this old disease are emerging as we move to
novelty and innovation era. We discuss in this review the advancements in this
disease entity highlighting and collecting the world experiences.
PMID- 29963398
TI - Four arms robotic-assisted pulmonary resection-left upper lobectomy: how to do
it.
AB - Numerous published articles have shown the safety and efficacy of robotic
anatomic pulmonary resection, including lobectomy for non-small cell lung cancer.
Several techniques have been described to perform a lung lobectomy robotically.
Since the beginning of our experience, we adopted a four-arm robotic approach
with the da Vinci Si System. More recently we have used the newer Xi model, that
offers a simplified and "quicker" set-up and docking time. This article emphases
specifically on the technical aspects of how to complete the hilar dissection
during four-arm robotic lobectomy.
PMID- 29963399
TI - Treatment of malignant pleural effusion.
AB - Malignant pleural effusion (MPE) is a very disabling condition that often affects
patients with advanced neoplasm. Conservative approach, repeated thoracentesis,
pleurodesis and use of indwelling pleural catheters (IPC) are the main methods to
deal with this condition. The ideal treatment must focus on symptom relief and
has to take into account patient underlying diseases, performance status and
necessity of adequate tissue sample for diagnosis. In a video we show techniques
to perform video assisted thoracic surgery (VATS) pleural biopsy and talc
poudrage pleurodesis.
PMID- 29963400
TI - Unilateral pulmonary vein atresia without anomalous connection in adult patient
with recurrent severe hemoptysis.
AB - Isolated unilateral pulmonary vein atresia (UPVA) is a rare congenital
malformation and the management remains controversial. In adults, pneumonectomy
is the treatment of choice when significant hemoptysis becomes life-threatening.
We report a case of a 28-year-old male with isolated unilateral right atresia of
the pulmonary vein who had life-threatening hemoptysis treated with bronchial
arteries embolization followed by successful right pneumonectomy.
PMID- 29963401
TI - Erratum to a glance at the history of uniportal video-assisted thoracic surgery.
AB - [This corrects the article DOI: 10.21037/jovs.2017.10.11.].
PMID- 29963402
TI - Robotic resection of a middle mediastinal mass.
AB - Aorto-pulmonary paraganglioma is an exceptionally rare condition, and its
diagnosis and treatment are a challenge for the general thoracic surgeon. We
describe the case of a 35 years old man who was incidentally diagnosed with a
visceral mediastinal mass, deeply encased in the aorto-pulmonary window. To our
knowledge this is the first case of its kind to be successfully treated with the
adoption of a minimally invasive technique. We conclude that the dissection was
made easier by the robotic instrumentation and by the camera system, and a
minimally invasive approach would have been more difficult by traditional
thoracoscopy.
PMID- 29963403
TI - Thoracoscopic management of early stages of empyema: is this the golden standard?
AB - Background: Empyema is a well-known disease that significantly increases the
morbidity and mortality associated with pneumonia. There are a number of
treatment modalities available but recently video assisted thoracoscopic surgery
(VATS) has been suggested as a reliable tool in management of empyema;
particularly in early stages. The aim of this study is to assess the safety and
effectiveness of using initial VATS for all surgically fit patients with early
stages of empyema. Methods: Sixty-six patients with early stage empyema were
prospectively studied between December 2013 and March 2016. Patients were divided
into two groups: group A (28 patients) were managed conservatively without
surgery for stage I (exudative) phase empyema by the chest physicians; and group
B (38 patients) were managed by the thoracic surgeons by VATS for stage I
(exudative) and stage II (fibrino-purulent) empyema. Comparison was made between
both groups. Results: There was no statistically significant difference between
the groups from the point of view of age, sex or pre-intervention comorbidities
(P>0.05). Average hospital stay in group A was 22 days (7-131 days), it was 4.1
days (2-14 days) in group B (P=0.004; 95% CI: 10.3-25.5) with a resultant lower
cost. Three patients (10.7%) in group A suffered from major morbidity during
treatment while none in group B suffered a major postoperative morbidity
(P=0.039). There were 2 mortalities (7.1%) in group A and no deaths in group B
(P=0.094). During a mean follow up period of 8 months [6-14] in group A 14.3% of
the patients underwent open decortication, whereas in group B, 5.3% of the
patients underwent the same procedure (P=0.047). Conclusions: Thoracoscopic
management of early stages of empyema should be the golden standard of management
in surgically fit patients; particularly in the fibro-exudative phase of empyema.
It is an effective and safe technique that reduces hospital stay, cost,
complications and avoids the need for a decortication via a thoracotomy in most
cases.
PMID- 29963404
TI - Robot-assisted en bloc anterior mediastinal mass excision with pericardium and
adjacent lung for locally advanced thymic carcinoma.
AB - Robot-assisted surgery for anterior mediastinal mass resection has been
increasingly adopted as an alternative method to open sternotomy and conventional
video-assisted thoracic surgery. However, more evidence is needed to expand the
indication of this technique to more complicated cases. We present a case of
robot-assisted en bloc resection of a 7-cm anterior mediastinal mass with
pericardium and adjacent lung for thymic squamous cell carcinoma, accompanied by
reconstruction of pericardium with polytetrafluoroethylene patch. In conclusion,
complex anterior mediastinal mass excision is feasible with robotic thoracic
surgery.
PMID- 29963405
TI - Endovascular repair of ascending aorta pseudoaneurysm.
AB - We present a case of a 48-year-old female patient with Marfan syndrome and
previous open surgeries for Bentall procedure and arch replacement with frozen
elephant trunk (FET) technique, who was admitted at our Department with a
diagnosis of ascending aorta pseudoaneurysm at the anastomosis-site between
composite valve graft and arch prosthesis treated by endovascular procedure
because of she was considered to be at high-risk for a third open surgery and for
the patient's favorable anatomy for endovascular closure of the pseudoaneurysm.
The patient was successfully treated with the positioning of two abdominal cuffs
through the left axillary artery. The postoperative course was uneventful and at
2-month follow-up, the patient was free of complications with CT angiogram
showing complete endovascular exclusion of the pseudoaneurysm.
PMID- 29963406
TI - What's New in Critical Illness and Injury Science? Case reports: The first step
on a path toward cure.
PMID- 29963407
TI - Evidence-based approach to the trauma patient in extremis: Transitioning from
exclusive emergency department thoracotomy use to protocolized approaches
incorporating resuscitative endovascular balloon occlusion of the aorta.
PMID- 29963408
TI - An evidence-based approach to evaluation and management of the febrile child in
Indian emergency department.
AB - Fever is the most common complaint for a child to visit hospital. Under the aegis
of INDO-US Emergency and Trauma Collaborative, Pediatric Emergency Medicine
chapter of Academic College of Emergency Experts in India developed evidence
based consensus for evaluation and management of febrile child in emergency
department. An extensive literature search and further online communication of
the group led to the development of a detailed approach for the evaluation and
management of individual conditions associated with fever. To develop an approach
to individual conditions presenting with fever, that is, best suited to the
epidemiology prevalent in India. The algorithmic approach given by the group
describes in details the evaluation and management of specialized and individual
conditions like fever and immunocompromised state, fever with localizing signs
that include fever with seizures, cough, ear discharge, loose stools, rash and
dysuria; fever without localization with epidemiological evidence supporting
diagnosis such as malaria, enteric fever and dengue; and fever without any
localization and no epidemiological evidence supporting the diagnosis.
PMID- 29963409
TI - Portal vein thrombosis: What surgeons need to know.
AB - Key points: (a) The lifetime risk of portal vein thrombosis (PVT) is
approximately 1%; (b) The portal vein is formed by the union of the splenic and
superior mesenteric veins posterior to the pancreas; (c) Imaging modalities most
frequently used to diagnose PVT include sonography, computed tomography, and
magnetic resonance imaging; (d) Malignancy, hepatic cirrhosis, surgical trauma,
and hypercoagulable conditions are the most common risk factors for the
development of PVT; (e) PVT eventually leads to the formation of numerous
collateral vessels around the thrombosed portal vein; (f) First-line treatment
for PVT is therapeutic anticoagulation-it helps prevent the progression of the
thrombotic process; (g) Other therapeutic options include surgery and
interventional radiographic procedures including mechanical thrombectomy and
thrombolysis; (h) Portal biliopathy is a clinicopathologic entity characterized
by biliary abnormalities due to portal hypertension secondary to PVT and appears
to be more common in cases of extrahepatic PVT. Republished with permission from:
Quarrie R, Stawicki SP. Portal vein thrombosis: What surgeons need to know. OPUS
12 Scientist 2008;2(3):30-33.
PMID- 29963410
TI - Prevalence of common nosocomial organisms in surgical Intensive Care Unit in
North India: A hospital-based study.
AB - Background: Nosocomial infection presents with high mortality rate, and it
remains a diagnostic and treatment challenge for health-care providers, with
developing countries having the highest incidence and mortality rates.[1]. Aim:
The present study was undertaken to evaluate prevalence of commonly isolated
nosocomial organisms in patients admitted in Surgical Intensive Care Unit (ICU)
in Government Medical College Srinagar. Materials and Methods: The study was
proposed to be conducted in surgical ICU of Shri Maharaja Hari Singh - a Tertiary
Care Hospital in Jammu and Kashmir (India) from March 2015 to March 2016. The
patients developing ICU infections within 48 h of admission in ICU or within 48 h
of transfer from ICU were included in the study. Results: Forty patients showing
different types of infections were included, 92 samples were collected which
included 39.13%, 27.17%, 8.70%, 7.61%, 10.87%, and 6.52% blood, urine, swab,
sputum, pus, and endotracheal tube (ETT) samples, respectively. From these
samples, 27.78%, 76.0%, 87.5%, 71.43%, 80.0%, and 33.33% samples of blood, urine,
swab, sputum, pus, and ETT, respectively, were found positive, i.e. showed the
growth of microorganisms. A total of 10 types of microorganisms were isolated
(Escherichia coli, Pseudomonas spp., Klebsiella spp., Acinetobacter spp.,
Staphylococcus aureus, Enterococcus, Enterobacter spp., Proteus spp., Citrobacter
spp., and Candida spp.) from six types of samples among which maximum number of
microorganisms were isolated from swab which was followed by blood and urine,
while minimum number of microorganisms were isolated from ETT. Further, among ten
microorganisms isolated, the highest percentage was recorded for Pseudomonas
spp., which was followed by Klebsiella spp. and E. coli, while the lowest
percentage was recorded for Proteus spp. Conclusion: There was a predominance of
Gram-negative bacilli than Gram-positive bacilli.
PMID- 29963411
TI - Antibiotic stewardship program in Intensive Care Unit: First report from Iran.
AB - Introduction: Few data regarding antibiotic stewardship programs in critically
ill patients are available. In the present study, the consequence of changing an
empirical antibiotic regimen from a carbapenem (meropenem) to a noncarbapenem
antibiotic (piperacillin-tazobactam) was evaluated in critically ill patients
with a suspicion of sepsis. Methods: This open-label randomized clinical trial
was conducted during May 2015-January 2017 at the general Intensive Care Unit of
the Imam Khomeini Hospital Complex, Tehran, Iran. In this study, a carbapenem
(meropenem) or a noncarbapenem (piperacillin-tazobactam) antibiotic was
considered as an empirical antibiotic regimen in 100 critically ill patients with
a suspicion of sepsis. Clinical response and bacterial eradication were defined
as primary and secondary outcomes of the study, respectively. Chi-square, Mann
Whitney, and independent sample t-tests were used for comparing variables between
the groups. ANOVA was used to compare changes in the mean differences of
parameters between the groups. Meaningful difference was indicated as P <= 0.05.
Results: During the first 72 h of the antibiotic course, the number of patients
with clinical response was comparable between piperacillin-tazobactam and
meropenem groups (21 [42%] and 25 [50%], respectively, P = 0.31). Also, at this
time, microbial eradication occurred in 13 (54.16%) and 9 (40.90%) patients in
piperacillin-tazobactam and meropenem groups, respectively (P = 0.67).
Conclusions: Using a carbapenem (meropenem) instead of a noncarbapenem
(piperacillin-tazobactam) as an empirical antibiotic regimen did not affect
clinical response and bacterial eradication rates in critically ill patients with
a suspicion of sepsis.
PMID- 29963413
TI - Ultrasound-guided peripheral nerve blocks in high-risk patients, requiring lower
limb (Above and below knee) amputation.
AB - A case series of five high-risk patients with lower limb ischemia, sepsis,
altered coagulation, and multi-organ dysfunction requiring emergent or urgent
lower limb amputation is presented. Use of peripheral nerve blocks for below and
above knee amputations is quite uncommon which provides better hemodynamic
stability and pain management, especially in the very sick patients. The
surgeries were successfully carried out under ultrasound-guided combined femoral
and sciatic nerve blocks. All five patients obtained adequate level of block at
the area of amputation. There were no complications related to anesthetic
management. Patients remained hemodynamically stable and pain-free during surgery
and postoperatively. Combined femoral-sciatic nerve block under ultrasound
guidance is safe and satisfactory alternative anesthetic technique for such
patients.
PMID- 29963414
TI - Clostridium perfringens empyema in a patient with metastatic squamous cell
carcinoma of the lung.
AB - We report a rare case of Clostridium perfringens (CP) empyema in a patient with
metastatic squamous cell cancer of the lung. Clostridial empyemas are rare and
clinically variable with some reports noting consequent necrotizing infections
and septic shock and others noting quick resolution with source control and
antibiotic treatment. This is the first case report to our knowledge to report a
CP empyema in a patient with lung malignancy. Given the comorbid lung malignancy,
the patient's presenting symptoms were mild with only mild shortness of breath,
fevers, and generalized weakness despite the large CP empyema. Early antibiotics
and source control with daily drainage of the pleural fluid allowed for
successful management, circumventing a complex critical care course and
successful management without ambulatory oxygen therapy on discharge.
PMID- 29963412
TI - Primary cecal pathologies presenting as acute abdomen and critical appraisal of
their current management strategies in emergency settings with review of
literature.
AB - Background: The importance of cecal pathologies lie in the fact that being the
first part of the large intestine, any disease involving the cecum affects the
overall functioning of the large bowel. Primary cecal pathologies presenting as
acute abdomen have not been described in any previous study in terms of
presentation, management, and outcome. Objectives: The objective of this study
was to identify the reported causes of primary cecal pathologies presenting as
acute abdomen and the various causes presenting in our setting, the to discuss
morbidity and mortality associated with cecal pathologies, and to critically
analyze the various management modalities employed in an emergency setting.
Materials and Methods: This is a retrospective analysis of a prospectively
collected data of all adult patients admitted to our unit in the last 10 years
for acute abdomen, in whom cecal pathology was identified as the primary
offending agent. Results: Our analysis of 43 patients revealed cecal perforation
secondary to amebic colitis along with the simultaneous presence of liver abscess
to be the most common primary cecal entity met in practice as acute abdomen.
Other pathologies that were encountered included volvulus, diverticulitis, and
idiopathic typhlitis. Primary acute cecal pathologies are associated with high
mortality rates (~42%). Delay in diagnosis seems to be the most important factor
contributing to high mortality as these conditions are commonly misdiagnosed as
appendicular pathology. Most of our patients were managed by conservative colonic
resection with proximal diversion. This seems to be a more plausible option in
current practice in an emergency setting (mortality rate ~ 36%) as hemicolectomy
is associated with proportionately higher mortality rates (67%). Conclusion: A
high index of suspicion, timely and adequate pre-operative workup, optimal
resuscitation, and surgical conservatism with proximal diversion might help in
early accurate identification of these conditions and possibly improved outcome.
PMID- 29963415
TI - Perioperative management of massive fat embolism syndrome presenting as
refractory status epilepticus.
AB - Fat embolism syndrome (FES) most commonly can occur after trauma in patients with
long bone fractures. While the majority of FES cases present as a mild decrease
in mental status, some may manifest as seizure activity. We describe a case of a
young patient with traumatic fractures who developed FES leading to refractory
status epilepticus and simultaneously required damage controlled orthopedic
surgery. The role of imaging modalities including magnetic resonance imaging,
transcranial Doppler, and transesophageal echocardiography in diagnosis is
discussed, and a multidisciplinary approach to successful perioperative
management is described.
PMID- 29963416
TI - Wild tuber poisoning: Arum maculatum - A rare case report.
AB - Arum maculatum, commonly known as wild Arum, is a woodland plant species of the
Araceae family. All parts of this plant are considered toxic. We report a case of
a young man who allegedly consumed poisonous wild tuber with suicidal intention.
He presented to our emergency department 3 h later with features of angioedema.
He was managed successfully with adrenaline and hydrocortisone. He was discharged
after 4 days of observation. Later, the wild tuber plant was identified to be A.
maculatum. We recommend that all patients who present with unknown substance
poisoning should be managed according to the principles of intensive care,
irrespective of the diagnosis.
PMID- 29963417
TI - On the Negative Outcomes of Craniofacial Surgery.
PMID- 29963418
TI - Unilateral Subcondylar and Condylar Neck Fractures: Randomized Clinical Study.
AB - Aims and Objectives: The aim of the present study was to compare closed treatment
with open reduction internal fixation (ORIF) for subcondylar and condylar neck
fractures. Materials and Methods: This randomized prospective study was conducted
on thirty patients who visited the Department of Oral and Maxillofacial Surgery,
Government Dental College, Srinagar, with condylar fractures. All fractures were
displaced; either angulated between 10 degrees and 45 degrees and the ascending
ramus was shortened by >2 mm to <15 mm. Patients were divided into two groups
after satisfying the inclusion and exclusion criteria - Group I (closed
treatment) and Group II (open reduction) (15 implants in each group). In Group I,
patients were treated by mandibulo-maxillary fixation using arch bar and elastics
for 4 weeks, and in Group II, patients were treated by ORIF using two 1.5-mm
miniplates. Follow-up was done at 1 month, 3 months, and 6 months. Our
postoperative evaluation included five parameters - maximal interincisal opening,
protrusion, lateral excursion on fractured and nonfractured sides, anatomical
reduction, and pain and malocclusion. Nonparametric data were compared for
statistical significance with Chi square test and parametric data with an
independent sample's t-test (P < 0.05). Results: Correct anatomical position of
the fragments was achieved significantly more accurately in the operative group
in contrast to the closed treatment group. Regarding mouth opening/lateral
excursion on fractured and nonfractured sides/protrusion, significant (P < 0.05)
differences were observed between both groups (open 39.73/7.50/8.17/7.87 mm vs.
closed 36.87/6.07/7.23/7.13 mm). Pain also revealed significant (P = 0.025)
difference with less pain in the operative treatment group. Conclusion: Both
treatment options for condylar fractures of the mandible yielded acceptable
results. However, operative treatment was superior in all objective and
subjective functional parameters except occlusion.
PMID- 29963419
TI - Soft Tissue Healing and Bony Regeneration of Impacted Mandibular Third Molar
Extraction Sockets, Following Postoperative Incorporation of Platelet-rich
Fibrin.
AB - Introduction: Surgical removal of impacted mandibular third molars is one of the
most commonly performed dentoalveolar surgeries by dental surgeons around the
globe. It is known to be associated with clinically significant postoperative
morbidity including swelling, pain, trismus, fever, and infection. In addition,
the residual bony defect takes 7 months to 1 year to gradually fill with bone and
to reossify. Aims and Objective: (1) To carry out a prospective study to evaluate
differences in soft tissue healing and bony regeneration of impacted mandibular
third molar extraction sites, with and without the incorporation of autologous
platelet-rich fibrin (PRF) within the surgical wounds. (2) To also compare the
incidence of short- and long-term posttreatment complications in both cases.
Materials and Methods: Sixty patients were randomly inducted into two groups,
consisting of 30 patients each. The first group, which served as the study group,
consisted of patients in whom fresh autologous PRF were placed within the
extraction site immediately following the surgical removal of the impacted
mandibular third molar, before suturing of the mucoperiosteal flap. The second
group, which served as the control froup, included those patients in whom the
mucoperiosteal flaps were closed without incorporation of PRF within site. Both
groups were evaluated and compared for postoperative pain, swelling, trismus,
soft tissue healing, as well as bone fill of the extraction socket. Results: It
was found that the study group in which autologous PRF had been incorporated into
the operative site exhibited quick and complication-free soft tissue healing as
well as a much quicker reossification and bone fill of the extraction socket, as
compared to the control group in which no PRF was used. Conclusion: Incorporation
of PRF within extraction sockets of impacted third molars proved to be beneficial
for patients, yielding a quicker postoperative recovery with fewer complications
such as postoperative swelling and edema, pain, and trismus; better overall
postoperative results in terms of faster soft tissue healing as well as an
earlier bony regeneration.
PMID- 29963420
TI - Condylar Fractures: Review of 40 Cases.
AB - Purpose: To put an algorithmic approach for the treatment of condylar fractures
according to the condition of occlusion. Patients and Methods: This study had
been carried out between May 2016 and April 2017. Forty patients were included (6
females and 34 males) with their ages ranged between 3 and 60 years. Patients
were managed through two approaches as follows: maxillomandibular fixation (MMF)
only regimen and MMF with open reduction and internal fixation regimen. The
operated cases were 12 with bilateral condylar/subcondylar fractures, and the
rest were unilateral 28 cases. Results: Data were assessed demographically, time
lapse before the intervention, surgically, functionally, and radiologically. In
general, there were no significant differences between closed and open methods.
Conclusion: Retromandibular approach was convenient for internal fixation of
condylar fracture with a good outcome. In our work, there were no significant
differences between closed and open methods in the treatment of condylar
fractures.
PMID- 29963421
TI - Wound Healing and Bone Regeneration in Postextraction Sockets with and without
Platelet-rich Fibrin.
AB - Context and Aim: In today's world of advanced dentistry, there are various
aspects of restorative, esthetic, and surgical processes. Healing of an
extraction socket comprises of bone as well as soft-tissue remodeling with
maximum dimensional changes occurring during the first 3 months. Platelet-rich
fibrin (PRF) was first developed in France as a therapeutic alternative to
platelet-rich plasma to overcome many of its limitations. The present study was
planned to evaluate and compare wound healing and bone regeneration in extraction
sockets with and without PRF. Materials and Methods: The present study was
carried out on 30 patients selected from the outpatient department over a period
of 21/2 years starting from May 2013 undergoing extraction of maxillary or
mandibular teeth simultaneously to conduct a split-mouth study. The research
protocol was approved by the Institutional Ethics Committee governing the use of
human subjects in clinical experimentation. Statistical Analysis Used:
Descriptive and analytical statistics were calculated using Statistical Package
for Social Sciences version 19. Chi-square test was used to assess wound healing
score in the two groups while paired t-test was used to compare the bone density
in the socket and periapical regions at different time intervals, and unpaired t
test was used for the intergroup comparisons. P < 0.05 was considered to be
significant while P < 0.001 was considered highly significant. Results: Patients
in PRF group had better healing index when compared to without PRF group. Use of
PRF showed a comparable increase in bone density too. Conclusion: An appreciable
wound healing and bone regeneration was seen in the experimental group when
compared to the control sites where no PRF was used substantiating the use of PRF
as an inexpensive autologous material for socket preservation and future
rehabilitation. The present study, also, showed that minimal operator expertise
was required to conduct the procedure of PRF preparation and grafting when
compared to bone harvesting from distant sites. The shorter duration between
extractions and further rehabilitation obviates the need for a second procedure.
PMID- 29963422
TI - Evaluation of Laser Tissue Welding and Laser-Tissue Soldering for Mucosal and
Vascular Repair.
AB - Context: Laser tissue bonding (LTB) is believed to have certain advantages over
conventional sutures such as fluid-tight closure and minimal scarring and
fibrosis. Aim: The aim of the present study was to evaluate the bond strength of
laser tissue welding and laser tissue soldering in mucosal and vascular repair.
Materials and Methods: A total of 85 samples of bovine oral mucosa and 85 bovine
aortas were bonded using a CO2 laser and different laser powers. Human serum
albumin was used as solder. The breaking load for mucosal samples and the
bursting pressure for aorta samples were evaluated. Few specimens were evaluated
histologically for thermal damage and other microscopic changes. Statistical
Methods: Two-way ANOVA was performed as the data were normally distributed and
analyzed for significant differences between the groups. This was followed by
Simple Main effects (Tuckey's post hoc test) to determine the individual
variation between groups and also the significant differences within the groups.
Results: Significantly higher values of breaking load (44.2 +/- 3.03 g) and
bursting pressure (70.8 +/- 12.33 mmHg) were noted when 50% albumin was used.
When reinforcing sutures were given the bond strength was further increased (68.0
+/- 4.0 g for breaking load) (108.0 +/- 12.56 mmHg for bursting pressure).
Microscopically, a bridge of solder coagulum formed across the wound. Thermal
damage was restricted to the top layers only although it did extend much more
laterally adjacent to the wound edges. Few areas of vacuolization and
carbonization were seen. Conclusion: LTB seems to be a promising new method of
wound closure and warrants further evaluation in the form of in vivo and clinical
studies.
PMID- 29963423
TI - Anthropometric Assessment of the Normal Adult Human Ear.
AB - Purpose: Knowledge of anthropometric measurements of the external ear is
important as variations exist based on gender, age and ethnicity. This study has
derived anthropometric data pertaining to the external ear in the Maharashtrian
population. Materials and Methods: Nine variables of the external ear were
measured in 505 Maharashtrian adults (aged 18-64 years) using photoanthropometric
methods. Results: Descriptive data and the left-right symmetry for the study
population were obtained. Conclusion: These data have applications in screening
for or monitoring diseases, otoplastic surgery, forensics, industrial design,
apparel design and ergonomics.
PMID- 29963424
TI - Facial Nerve Injury in Temporomandibular Joint Approaches.
AB - Facial paralysis can be a devastating consequence resulting from blunt and
penetrating trauma to the head and neck, as well as surgical injury, either
accidental or due to involvement by tumor. In addition, the etiology can be
attributed to a variety of other causes, ranging from infectious to metabolic,
and is frequently idiopathic in nature. The incidence of facial nerve injury
during temporomandibular joint (TMJ) surgeries varies among surgeons. There are
many factors that could contribute to the injury of the temporal and zygomatic
branches of the facial nerve. These nerves lie in a confluence of superficial
fascia, temporalis fascia, and periosteum and may be injured by any dissection
technique that attempts to violate the integrity of these regions. Excessive or
heavy-handed retraction causes compression and/or stretching of nerve fibers
resulting in neuropraxia. The facial nerve then enters the parotid gland, where
the main trunk branches into the upper and lower divisions at the pes anserinus.
The nerve further divides into five main branches: the temporal, zygomatic,
buccal, marginal mandibular, and cervical. The temporal branch lies within the
superficial muscular aponeurotic system at the level of the zygomatic arch. In
this paper, we evaluate the facial nerve function based on the House-Brackmann
grading index after the preauricular approach for the treatment of condylar
fractures, pathologies, and TMJ ankylosis cases. The nerve functional
regeneration postfacial nerve injury has been evaluated and reported in this
retrospective study.
PMID- 29963425
TI - Management of the Frontoethmoidal Encephalomeningocele.
AB - Introduction: The Frontoethmoidal encephalomeningocele (FEEM) is a congenital
neural tube anomaly, with herniation of intracranial material such as the brain
and leptomeninges through a defect of the dura and anterior skull base at the
junction of the frontal and ethmoidal bones. It may result not only in neural
defects, sensorimotor deficits, neurological morbidities, visual impairment,
impaired nasal function, and a potential risk of intracranial infection, but also
in significant craniofacial disfigurement with complex deformities in the
frontal, orbital, and nasal regions. Materials and Method: The standard two
staged surgical protocol comprises of the first stage performed by a
neurosurgeon, which aims at correcting the neural defect by a formal craniotomy;
then the second stage performed by a craniomaxillofacial or plastic and
reconstructive surgeon, to correct craniofacial hard and soft tissue deformities.
The case discussed was managed using a modified intracranial-transcranial single
stage approach, achieving both the desired objectives. Results and Conclusion:
This protocol elucidates the importance and value of teamwork between the
Neurosurgeon and Craniomaxillofacial surgeon, in comprehensively and efficiently
managing small to moderately sized FEEMs, assuring their complete elimination,
satisfactory defect closure, effective functional treatment as well as esthetic
correction and reconstruction of the attendant craniofacial deformities by means
of a single-stage definitive surgical approach.
PMID- 29963427
TI - Vascular Analysis of Radial Artery Perforator Flaps.
AB - Background: Radial forearm free flap with all its present day modifications is
the workhorse of soft tissue reconstruction in head & neck. Although there are
several advantages, it requires the sacrifice of a major artery of forearm. There
are several modifications of harvesting a forearm flap based on perforator
principles. A clear understanding of vascular anatomy of individual perforators
relative to its vascular territory & flow characteristics is essential for both
flap harvest & design. The purpose of this cadaveric observational anatomical
study was to determine the location, size & vascular territory of the radial
artery cutaneous perforators. Materials and Methods: 12 fresh human cadavers & 24
cadaveric forearms were dissected to determine the total number, location, size &
vascular territory of radial artery adipo-fascio cutaneous perforator. The
cutaneous territory of distally dominant perforators was analyzed using methylene
blue injections & three-dimensional computed tomographic angiogram. Results: In
the 12 fresh human cadavers & 24 forearm specimens, a total of 222 perforators
were dissected for an average of 18.5 radial artery perforators per forearm. Of
the total 222 perforators dissected 118 were smaller than 0.5mm in diameter
(53.15%) these were not clinically significant. 104 perforators were greater than
0.5mm in diameter (46.84%) these were clinically significant. Of the 222 radial
artery perforators dissected, 127 perforators (57.20%) were radially distributed
& 95 perforators (42.79%) had ulnar distribution. A total of 90 perforators
(40.54%) were identified on distal side (Radial styloid) & 132 perforators
(59.45%) were identified on proximal side (Lateral epicondyle). Mean number of
perforators on radial side was 10.6 & 7.9 on ulnar side, a comparison of both
using student t paired test gives a P value of 0.006, which was statistically
significant. Comparison of mean number of perforators on the distal side was 7.5
& proximal side was 11.0, Student Paired t test gives a P value of 0.003, which
was statistically significant. Comparison of mean Diameter of perforators between
the Distal side (1.11) & Proximal side (0.86) using Student Paired t test gives a
P value of 0.01 which was statistically significant. A chi square test was done
to compare mean diameter of perforators on distal side, which were more than 1mm
(80%) & less than 1mm (20%) & on proximal side more than 1mm (35.6%) & less than
1mm (64.4%). Chi square value of 42.406 was obtained, degree of freedom value was
1& P value of <0.001 was achieved which was found to be highly significant.
Methylene blue injections into the proximal part of radial artery demonstrated
clusters both in proximal & distal forearm & also cutaneous territory of flap.
Three- dimensional computed tomographic angiography reveals a network of linking
vessels found to communicate between adjacent perforators & running parallel to
radial artery. Large network of linking vessels could be found between fascia &
dermis, which also explains the ability to harvest forearm flap at the supra
fascial level. Conclusion: Increase in knowledge of vascular territory of radial
artery perforators with regards to numbers, size, location, and cutaneous
territory can lead to expanded use of radial forearm flap based on either distal
or proximal perforator alone, without sacrificing the radial artery.
PMID- 29963426
TI - Medial Sural Artery Perforator Flap for Head and Neck Reconstruction.
AB - Aim: The aim is to study the assessment of feasibility of medial sural artery
perforator (MSAP) free flap for head and neck reconstruction at our center.
Materials and Methods: Oral cancer patients with squamous cell carcinoma of the
tongue, buccal mucosa, and floor of mouth cancer attending our center were
reconstructed using MSAP flap after oncologic resection. Handheld 8 MHz Doppler
was used to identify the perforator preoperatively. Results: We reconstructed 10
patients using MSAP flap. The flap was designed according to defect and donor
site was primarily closed in all cases. Excellent results were seen in nine
patients reconstructed with MSAP flap without any postoperative complication.
Flap failure occurred in one patient due to venous thrombosis. The thickness of
flap ranged from 4 to 8 mm. The vascular pedicle length ranged from 9 to 13 cm.
Conclusion: The MSAP flap is appropriate for medium-sized oral defect
reconstruction, with a long pedicle of matching caliber, adequate tissue volume,
and minimal donor-site morbidity which makes it comparable to other microvascular
free flaps such as radial artery free flap (RAFF) and anterolateral thigh flap.
PMID- 29963428
TI - Three-dimensional Locking Plate and Conventional Miniplates in the Treatment of
Mandibular Anterior Fractures.
AB - Context: Three-dimensional (3D) locking plates has been designed with the
hypothesis that this will overcome the disadvantages of both the systems and also
advantages of both systems will be combined for the management of mandibular
fractures. Aims: The purpose of this study was to evaluate the efficacy of 2-mm
3D locking miniplate in the management of anterior mandibular fracture and to
compare it with Champy's miniplate. Settings and Design: A prospective,
randomized, clinical trial was carried out in thirty patients who were divided
equally in two groups. Subjects and Methods: Group I and Group II patients were
treated with 2-mm 3D locking plates and 2-mm standard miniplates, respectively.
They were evaluated according to the outcomes of the study, that is, working
time, wound dehiscence, infection, segmental mobility, postoperative occlusion,
need for postoperative intermaxillary fixation (IMF), and radiological evaluation
of reduction and fixation. Statistical Analysis Used: Student's t-test and Mann
Whitney test were used to compare the two systems. The data were analyzed using
Statistical Package for the Social Science version 14.0. The P value was taken as
significant when <0.05 (confidence interval of 95% was taken). Results: The mean
duration of procedure for Group I was found to be 49.33 min, whereas for Group II
was 59.67 min. There was significantly greater pain on day 1 and at 1 week in
Group II patients. 6.7% (n = 1) of both groups showed incidence of infection.
Postoperative stability was adequate in most cases except in one patient (n = 1)
of 3D locking system, which was revealed as postoperative occlusal disharmony,
unsatisfactory radiological reduction of the fracture fragments, and the
segmental mobility. There was no incidence of wound dehiscence, tooth damage, and
nerve damage in either group. Conclusions: The result of the study can conclude
that there is no major difference between both systems in terms of treatment
outcome.
PMID- 29963430
TI - Patient Perception following Alloplastic Total Temporomandibular Joint
Replacement.
AB - Introduction: A retrospective analysis was done on patients who had undergone
unilateral temporomandibular joint reconstruction using alloplastic
temporomandibular prostheses. Aim: The study wished to highlight patient
perceptions after surgery; specifically relating to pain, function, and
aesthetics. Material and Method: Twenty three patients were assessed using a
visual analogue scale (VAS) for pain, ability to eat, quality of life and scar
appraisal. Results: Patients Vas scores were favourable for all parameters save
for scar appreciation. Conclusion: Total temporomandibular alloplastic joint
replacement is a viable treatment option, with generally positive surgical
outcomes for patients.
PMID- 29963429
TI - Retrospective Study of Facial Fractures.
AB - Aim: The aim of this study was to give an insight into the retrospective analysis
of a number of maxillofacial trauma cases reported to our institute and research
center. Materials and Methods: The data for this study was obtained from the
medical records and outpatient prescription slips of cases treated at the Oral
and Maxillofacial Surgery Department from 2010 to 2016. Etiology, age, gender,
pattern of fracture, and surgical treatment modalities undertaken in these
patients were recorded. Results: A total of 353 maxillofacial trauma patients
with mean age of 40 years, treated at our institute were evaluated from 2010 to
2016. Mandible was the most commonly fractured bone with parasymphysis as the
most frequent site. Majority of victims were males (male:female ratio of 4:1) and
also in the third decade of life. This study showed that 73% patients were
treated by open reduction and internal fixation (ORIF), 25.8% by intermaxillary
fixation (IMF) and Stabilization of fracture mandible with acrylic splint and
circummandibular wiring was done in 0.8% pediatric patients. Conclusion: It was
concluded that road traffic accidents were reported as the leading cause of
maxillofacial fractures followed by assault, falls, and familial dispute.
Maxillofacial surgeons as health care providers must continue their 'face it'
campaign to decrease the incidence of road traffic accidents. Open reduction and
internal fixation remains the gold standard treatment modality.
PMID- 29963431
TI - Access to the Skull Base - Maxillary Swing Procedure - Long Term Analysis.
AB - Background: Skull base is difficult to approach surgically due to its complex
anatomy. A number of procedures that is endoscopic, microscopic, and open
approaches have been used. The maxillary swing approach provides a wide exposure
to the surgeon for better oncological clearance. Patients and Methods: A total of
62 patients with varied etiologies involving the skull base region were operated
with maxillary swing procedure over a period of 15 years from 2001 to 2016 in
plastic surgery department at a single institution. Results: There was no
recurrence in the follow-up period. One patient had palatal fistula and one
patient had mild nasal mucosal atrophy. None of the patients had malocclusion in
the postoperative period. The minimum follow-up period was 24 months. Conclusion:
Maxillary swing procedure provides excellent exposure to skull base, and most of
the tumors involving this region can be effectively excised with minimal
morbidity to the patient.
PMID- 29963432
TI - Burden of Orofacial Clefting in India, 2016: A Global Burden of Disease Approach.
AB - Background: In the recent past, there have been inconsistent reports of India
witnessing a decreasing trend in the incidence of orofacial clefts (OFC). To
date, little comprehensive evidence has been published. To identify the
prevalence, associated burden in terms of epidemiological parameters and to
estimate the "unmet" OFC treatment needs, the present study was undertaken.
Materials and Methods: Using the Global Burden of Diseases 2016 approach and its
assumptions, an attempt was made to estimate the prevalence to quantify the
burden of OFC in India as disability-adjusted life years (DALYs), years of life
lost (YLL), and years lived with disability (YLD) as well as death due to OFC.
The results from such an approach are presented. Using previous estimates of
"unmet" OFC treatment needs, an attempt was made to estimate the current volume
of "unmet" OFC treatment needs. Results: In the present study, it was estimated
that a total of 0.033% of all Indian population suffers from OFC. In 2016, the
estimated prevalence rate/100,000 was 33.27 for males, 31.01 for females, and
32.18 combined for both genders. It was estimated that for all ages, the DALYs
lost were 2.05 for 100,000 males, 2.66 for females and 2.34 for both sexes. The
OFC birth prevalence model revealed that the birth prevalence (as a proportion)
in 2016 in India showed an odds ratio of 0.48 (1.56-1.65) and fixed factor of
nonrecording 0.83 (0.15-6.63), underreporting 0.97 (0.88-1), gender 1.09 (1.02
1.16), chromosomal diagnoses included 1.22 (1.22-1.22), and stillbirth 1.22 (1.22
1.22). The total unmet cleft treatment need was estimated at 79,430 or 18.76% of
the total Indian cleft population with OFC. Conclusions: Within the constraints
of the mathematical modeling and based on all available surveys, literature, and
reported data, the overall birth prevalence and the prevalence of OFC in India
are presented. Till reliable data emerges, the present estimates could serve as a
robust estimate of the prevalence and burden of OFC in India. The present
enterprise highlights the need for well-designed, high-quality Pan-India,
community-based, observational studies to accurately estimate the burden of OFC
in India.
PMID- 29963433
TI - Critical Appraisal Regarding the Publication "Implant Survival between Endo
Osseous Dental Implants in Immediate Loading, Delayed Loading, and Basal
Immediate Loading Dental Implants: A 3-Year Follow-Up" as Published in Ann
Maxillofac Surg 2017;7; 237-44, by the Authors R. Gharg (Corresponding Author),
Neha Mishra, Mohan Alexander, Sunil K. Gupta.
AB - This article analyses published prior article regarding the questions: is the
study setup correct (true) and if comparable cases are evaluated for the compared
methods. Futhermore the content, the pictures, the tables, the graphs and the
pictures legends of the article and statistics are analysed for truth, relevance
and applicability. We investigate furthermore if this article addresses all
relevant questions regarding bias, the study groups, the evaluation of the
outcomes and the evaluation of patient parameters such as burden of the
treatment. As a result of the analysis, we state that the analysed article is
misleading and it does not provide valuable information regarding decision making
for other healthcare professionals in the dental implant field.
PMID- 29963434
TI - Ameloblastomatous Calcifying Odontogenic Cyst: A Rare Entity.
AB - Introduction: Ameloblastomatous calcifying odontogenic cyst (COC) is an extremely
rare histopathologic variant of COC, an odontogenic cyst of the jaws. It needs to
be differentiated from closely associated variant ameloblastoma ex COC that is
entitled to a more aggressive form of surgical management. Aim: The aim of this
paper is to present a case of ameloblastomatous COC of the right mandibular angle
region with review of literature describing this rare entity. The paper also
highlights the requirement of including this lesion in differential diagnosis of
various jaw lesions. Materials and Methods: Google search, Wikipedia,
ScienceDirect, MEDLINE, the Cochrane library, and PubMed were used extensively to
search and collect all reported cases of ameloblastomatous COC using keywords
such as ameloblastomatous COC, COC, maxilla, mandible, and gorlin cyst
ameloblastic proliferation. Results: To the best of our knowledge, a total of
twenty one cases of ameloblastomatous COC have been reported in the literature in
the maxilla-mandibular region and we represent the twenty second case in a 20
year-old female patient along with the review. Conclusion: Ameloblastomatous COC
a subtype of COC needs to be differentiated from true ameloblastoma arising from
COC as it warrants a conservative form of surgical management unlike other
neoplastic variants of COC. Owing to scarcity of data of this lesion in
literature, more reporting of such cases is required to shed light on its
behavior.
PMID- 29963435
TI - Osteosynthesis Using the Uncalcined and Unsintered Hydroxyapatite / Poly-L-Lactic
Acid System.
AB - The poly-L-lactic acid mini-plate system accomplished rapid development. However,
the system still has a variety of problems. One such problem is the breakage of
screws. In this technical report, we develop the temporary fixing screws made
from stainless with hexagon steel that exhibit a hexagonal head and thread part
that also features a tapping function.
PMID- 29963436
TI - Acceleration of Intruding Anterior Tooth by Alveolar Corticotomy.
AB - True intrusion is one of the difficult and complex goals to achieve which
requires clinical judgment, skills, and experience. Intrusion requires less force
level than other tooth movement, but it requires delicacy since the entire stress
is concentrated in the apex of the root. Although true intrusion alone is not
challenging, eliminating the adverse effect while intruding requires tedious
skills of the clinician. A 17-year-old male patient with Class I malocclusion
with open bite has a prominent maxillary cortical bone. He had a convex profile
with an unpleasant smile. To reduce the bulkiness of cortical bone and to intrude
the upper anterior, so the decision was made to perform corticotomy.
PMID- 29963437
TI - Neurofibromatosis Type 1 in the Mandible.
AB - Neurofibromatosis type 1 (NF1) was first described in 1882 as a hamartomatous
disorder of neural crest derivation. We present the imaging of a 65-year-old
woman with NF1. Computed tomography revealed that there were three major findings
presented: skeletal deformity, an area of fat (probably related to mesodermal
dysplasia), and benign neoplasm within the masticator space. Moreover,
masticatory muscles were hypoplastic.
PMID- 29963438
TI - Large Pleomorphic Adenoma of Hard Palate.
AB - Pleomorphic adenoma (PA) is a benign tumor of the salivary glands commonly seen
in the parotid and submandibular salivary glands. Rarely, it is seen in the minor
salivary glands located at lips, palate, and other parts of the upper
aerodigestive tract. We report a case of an unusually large PA of the hard palate
in a female patient involving left maxillary sinus and nasal cavity. After
excising, the tumor with adequate clinical margins (1 cm), a large postsurgical
defect was managed by the use of obturator and it gradually healed by secondary
intention in about 6-month period. The unique feature in our case was that in
spite of the long duration of the tumor (30 years), it did not undergo malignant
transformation.
PMID- 29963439
TI - Odontome, Cyst, Impacted Tooth, and Space Infection in a Single Patient: All-in
One Diagnostic Dilemma.
AB - This case report analyzes the clinical and radiographic features of odontogenic
infection with underlying pathology. Systematic approach leads to narrow the
differential diagnosis on the basis of exclusion. This results in correct
diagnosis, proper treatment, and avoiding unnecessary treatment. This case report
highlighted an unusual case of odontogenic infection involving adjacent fascial
spaces with underlying pathology which was mimicking a cyst, tumor, and odontome.
Systematic approach helped us achieve accurate diagnosis, treatment, and avoiding
complications.
PMID- 29963440
TI - Dandy-Walker Syndrome with Giant Cell Lesions and Cherubism.
AB - It has been very aptly quoted, "Variety is the spice of life"; and so variations
exist in all forms and kinds good or bad, and for the worst or the best! Mother
nature in all her glory and beauty has been very generous, but what when she
fails to provide? It is this very character of nature that gives us variations
which sometimes manifest in a cruel way on the human body and gives us the eponym
of syndromes. Dandy-Walker malformation is an abnormality of the central nervous
system, which leads to hydrocephalus and is associated with other abnormalities.
Neurologic symptoms are the norm in afflicted patients due to the inherent nature
of the disease in that it affects the very center of human function-the brain.
This article brings to you a very unique, challenging and rare case of a young
patient with this debilitating disorder who was also affected with giant cell
lesions of the maxilla and mandible along with cherubism. It highlights the
unpredictable course and progression of the disease in a child and our unique
protocol employed for the management of the same. It adds providence and a new
perspective to the still ambiguous nature of this disorder and the unprecedented
maxillofacial anomalies, i.e., giant cell lesions and Cherubism associated with
the same.
PMID- 29963441
TI - Sebaceous cyst in the oral cavity.
AB - Sebaceous glands are reported to be normally located in the oral region in the
vermilion of the upper lip and on the buccal mucosa. They are small yellowish
bodies located immediately beneath the mucosa, and although numerous pathologies
of these tissues have been described, very few clinical reports have been made.
Pathologies such as ectopic location, hyperplasia, adenomas, carcinomas, and
cysts have been described. If an excretory duct suffers a dilatation which does
not regress of its own accord, it may originate a cyst. The purpose of this
clinical report is to describe a free sebaceous cyst located in the upper lip.
PMID- 29963442
TI - Reconstruction of the Parotid Duct.
AB - The most common causes of parotid duct lesions are injuries with sharp
instruments. Late alterations after such lesions lead to esthetic defects and
complicates the treatment. This case report presents an alternative surgical
technique for late reparation of the parotid duct. A 31-year-old male patient was
admitted with a history of physical aggression by a glass bottle, resulting in
cutting injuries in face and drainage of extraoral transparent fluid from the
buccinatory region lesion Antibiotic therapy was initiated immediately, and the
surgery was performed nine days after the incident. The repair of the parotid
duct lesion was achieved adapting a venous catheter that was passed through the
distal portion of the duct from the oral orifice. The proximal segment of the
duct was cannulated, the lacerated ends of the duct were approximated on the
device and sutured with prolipopylene thread. At the 14-day post-operative
return, the saliva was draining through the catheter, and then it was removed.
Patients with cutaneous lesions in the buccinatory region require a thorough
examination to identify injuries to the parotid duct. The surgical treatment
using the presented alternative surgical technique was an effective and cheaper
option when compared to other alternatives and showed no complications.
PMID- 29963443
TI - Numb Chin as Signal for Malignancy-Primary Intraosseous Diffuse Large B-Cell
Lymphoma of the Mandible.
AB - Malignant lymphomas are about 5% of all malignant tumors. Extranodal non
Hodgkin's lymphomas (NHLs) are found in 26% of these cases. Lymphomas of the head
and-neck area occur in 2%-3% of all malignancies, with 28% with an extranodal
manifestation. Extranodal NHLs in the oral cavity are usually found in the
maxilla, and rarely in the mandible. Their symptoms and clinical manifestation
have no pathognomonic features; therefore, the expression of this uncommon entity
can be diagnosed with an odontogenic inflammatory process, leading to a
misdiagnosis. Delay in the decision for a biopsy, and adequate treatment for the
patient directly impairs the prognosis of this neoplasm. This study reports a
case of a patient with discomfort in the right mandible and paresthesia of the
right lower lip and chin without any dental focus. After performing further
diagnostic examinations including a subsequent biopsy, the final diagnosis was a
diffuse large B-cell lymphoma (DLBCL). Intraosseous DLBCLs are uncommon in the
daily clinical routine, but emphasize the need for careful examination by the
clinicians also considering the differential diagnosis of sensory neuropathy.
Neurological symptoms with no apparent cause should raise the suspicion of
malignancy until the opposite is proven.
PMID- 29963444
TI - Juvenile Ossifying Fibroma in the Mandible.
AB - Juvenile ossifying fibroma is a rare benign fibroosseous tumor which involves
maxilla more than mandible. It usually occurs in children below 15 years of age.
This article reports a case occurring in the mandible with the surgical treatment
followed by us.
PMID- 29963445
TI - Hemangiopericytoma/Solitary Fibrous Tumor of the Buccal Mucosa.
AB - Hemangiopericytomas (HPCs)/Solitary fibrous tumor are rare neoplasms of vascular
origin that occur in head-and-neck region. These tumors arise from capillary
pericytes and are difficult to distinguish from other tumors of vascular origin.
HPC, initially described by Stout and Murray in 1942, usually occur in the fifth
decade of life and account for 3%-5% of all soft-tissue sarcomas and 1% of all
vascular tumors. The tumors usually occur in limbs, pelvis, or head-and-neck
region; 15%-30% of all HPCs occur in head and neck. We report a case of HPC
located in the right buccal area of a 60-year-old man.
PMID- 29963447
TI - Zygomatico-coronoid Ankylosis as Sequel of Inadequate Treatment.
AB - Temporomandibular joint ankylosis may be true or false. Most commonly, trauma and
inflammatory conditions lead to this condition. Zygomatico-coronoid ankylosis is
a rare extra-articular (false) form of ankylosis of the jaw. This condition may
follow treated or untreated midface fractures. Coronoid process locking may be
overlooked because attention is generally focused on temporomandibular joint. A
review of literature has reported 16 cases of this disorder. The true incidence
of this condition may be even higher. In this paper, we present an unusual case
of posttraumatic bony ankylosis of the right coronoid process of the mandible
with the zygomatic arch in a 30-year-old male. This bony ankylosis was produced
by a mass of heterotopic bone formed, following inadequate treatment of midfacial
fracture. Extra-oral ostectomy of the ankylotic mass followed by immediate
postsurgical aggressive physiotherapy produced good long-term functional outcome.
PMID- 29963446
TI - Management of the Bilateral Chronic Temporomandibular Joint Dislocation.
AB - Temporomandibular jaw dislocation is an uncontrolled anterior movement of the
condyle beyond the articular eminence. It can occur mostly in young adults, and
the symptoms are mouth opening disturbance, preauricular skin depression, tense
masticatory muscles, and pain. The main purpose of the eminectomy procedure is
removal of a part of the articular eminence to maintain free movement of the
condyle. The surgical procedure may be performed by conventional surgery or
piezosurgery. The present case report describes the management of a recurrent
mandibular dislocation in a 28-year-old patient who had also treated
conservatively with autologous blood injection. In this report, bilateral
eminectomy was performed by piezosurgery to provide soft-tissue protection,
precise cut, and optimal view of the surgical area. The management technique is
discussed within the current literature.
PMID- 29963448
TI - Autogenous Dermis-fat Graft in Temporomandibular Joint Ankylosis Surgery.
AB - Temporomandibular joint (TMJ) ankylosis is fusion or a bony union of the head of
the condyle and the glenoid fossa by bony or fibrotic tissues. Due to the
immobility of the TMJ, all mandibular movements get affected. Treatment goals are
to allow nearly normal TMJ movements, restore symmetry of the face and occlusion,
and promote growth and correction of deformity in children. The surgical
techniques used to treat TMJ ankylosis are a gap or interpositional arthroplasty,
joint reconstruction, and distraction osteogenesis. Appropriate interposition
materials include autogenous tissues, allogeneic tissues, and alloplastic and
xenograft tissues. This report presents the treatment of a patient with a
diagnosis of TMJ ankylosis, who had failed surgery. Interpositional autogenous
dermis-fat graft was used to manage TMJ ankylosis of the right side. The
technique is discussed within the current literature.
PMID- 29963449
TI - Unusual Cause for Maxillofacial Injury.
AB - Penetrating facial injuries are potentially dangerous and may require emergency
management because of the presence of vital structures in the face, and it may be
life-threatening especially when the injury involves airway, major blood vessels,
spinal cord, and cervical spines. Penetrating injuries of the facial region can
occur due to missile injuries, blast injuries, motor vehicle accidents, and
accidental fall on sharp objects. However, injury to face caused by the
shattering of a protective helmet itself is extremely rare. Primary management is
targeted to deal with life-threatening conditions and stabilize the patient
followed by subsequent care in a well-equipped setting. We present a case of a 30
year-old male, who suffered extensive soft and hard tissue injury of the
maxillofacial region due to shattering of a protective helmet causing a ballistic
effect.
PMID- 29963450
TI - Rare Mandibular Ramus Fracture.
AB - Mandibular fractures represent approximately two-thirds of all maxillofacial
fractures (nearly 70%), out of which fractures of mandibular ramus represent
3.09% which is considered to be a rare fracture site. They occur alone or in
combination with other facial bone fractures resulting in loss of function and
disfigurement. The pattern of mandibular fractures varies with geographic
location, physical activity, social, cultural, and environmental factors. The
main causes of mandibular fracture are road traffic accidents, interpersonal
violence, falls, sports injuries, industrial trauma, and pathological fractures.
In this clinical case, the authors describe a vertical ramal fracture extending
from subsigmoid region to inferior border of angle of the mandible combined with
symphysis fracture which was surgically operated through open reduction and
internal fixation by extraoral approach.
PMID- 29963451
TI - Critical Appraisal --- The Response.
PMID- 29963452
TI - Note of Concern.
PMID- 29963453
TI - Striking Multiple Primary Tumors that underwent Whipple Procedure due to
Periampullary Carcinoma: An Analysis of 21 Cases.
AB - Introduction: The term multiple primary tumor (MPT) is used to describe cases
where two or more primary tumors show no histopathological similarities in
between. Multiple primary tumor cases have begun to increase in recent years as a
result of the increase in life expectancy because of the increase in life
standards and progress in diagnostic methods. In this study, MPT cases with
periampullary tumors that underwent Whipple procedure were discussed in the light
of literature data. Materials and methods: The patient files of 223 cases with
periampullary tumors that underwent Whipple procedure in our hospital during the
last 6 years were examined retrospectively. More than one primary tumor was
detected in 21 patients. Results: Periampullary carcinomas were detected as a
second primary tumor in 18 patients. First primary tumor was periampullary
carcinoma in 3 patients that underwent Whipple procedure. After the Whipple
procedure, 5 patients died due to early complications in the first 30 days and 6
patients died due to metastases and additional problems that developed during
follow-up. Discussion: The incidence of MPT has been reported as 0.7 to 14.5% in
the literature. Most of them are multiple primary case presentations. In patient
management, it is recommended that each tumor should be evaluated independently
of its own characteristics, and treatment and follow-up should be planned
accordingly. Conclusion: The MPT cases are increasing. The possibility of MPT as
well as metastasis should be kept in mind during the evaluation of tumor foci
seen during diagnosis and follow-up of patients. The characteristics of each
tumor, survival, and prognosis should be evaluated separately and the most
appropriate treatment should be offered to the patient. It is recommended that
synchronic primary tumors which are considered to be surgically resectable
without metastasis should be removed in the same session.How to cite this
article: Dilek ON, Ozsay O, Karaisli S, Gur EO, Er A, Haciyanli SG, Kar H, Dilek
FH. Striking Multiple Primary Tumors that underwent Whipple Procedure due to
Periampullary Carcinoma: An Analysis of 21 Cases. Euroasian J Hepato
Gastroenterol 2018;8(1):1-5.
PMID- 29963454
TI - Primary Gastric Lymphoma: Clinicopathological Profile.
AB - Introduction: Gastrointestinal tract (GIT) is the most common site of involvement
of extranodal non-Hodgkin's lymphoma (NHL). There is regional variation in
anatomical distribution of extranodal NHL, stomach being the most common site
followed by small intestine. Primary gastric lymphoma (PGL) predominantly
involves the antrum and corpus of the stomach. It arises from mucosa-associated
lymphoid tissue (MALT) and is of B-cell lineage and often associated with
Helicobacter pylori infection. Primary gastric lymphoma often presents with
nonspecific symptoms. The present study was undertaken to ascertain the
clinicopathological characteristics of PGL at a tertiary care center in South
India. Materials and methods: It is a retrospective study from 2006 to 2016.
Patient's data were obtained from institutional medical records. The
histopathology slides were reviewed. The relevant immunohistochemistry (IHC)
markers done were leukocyte common antigen (LCA), CD3, CD20, CD79a, CD10, Bcl-2,
Bcl-6, CD5, Cyclin D1, CD138, and Ki-67. Correlating with the immunoprofile,
further subtyping was done. Results: A total of 405 patients of NHL were seen
during the study period, out of which 43 patients were PGL. There were 32 males
and 11 females, with M:F of 2.9:1. The mean age at diagnosis was 58 years.
Abdominal pain and new-onset dyspepsia were the commonly observed presenting
symptoms. The common site of involvement was antrum (20). Diffuse large B-cell
lymphoma (DLBCL) was the most common histological subtype. Helicobacter pylori
infection was seen in 18 (41%) patients. Majority of the patients were in stages
II and III. Conclusion: In our study, the initial presentation of PGL was with
nonspecific symptoms like abdominal pain and new-onset dyspepsia. High degree of
suspicion of such symptoms and biopsy of all suspicious lesions is essential for
early detection. Diffuse large B-cell lymphoma was the most common histological
subtype seen in our study.How to cite this article: Malipatel R, Patil M, Rout P,
Correa M, Devarbhavi H. Primary Gastric Lymphoma: Clinicopathological Profile.
Euroasian J Hepato-Gastroenterol 2018;8(1):6-10.
PMID- 29963455
TI - Intake of Bifidobacterium longum and Fructo-oligosaccharides prevents Colorectal
Carcinogenesis.
AB - Introduction: We aimed to investigate the effects of intake of yogurt containing
Bifidobacterium longum (BB536-y) and fructo-oligosaccharides (FOS) in preventing
colorectal carcinogenesis in healthy subjects, and the preventive effects of
short-chain fatty acids (SCFA), whose production was enhanced by the intake of
BB536-y and FOS, in human colon cancer cell lines. Materials and methods: The
subjects were 27 healthy persons who were divided into a group taking yogurt
containing BB536 (BB536-y group; n = 14) and a group taking yogurt containing
BB536 and FOS (BB536-y with FOS group; n = 13) once a day for 5 weeks. The feces
were sampled before and after the intake to analyze the amount of SCFA in the
feces and the profile of intestinal flora, such as putrefactive bacteria and
Bacteroides fragilis enterotoxin (ETBF). Subsequently, human colon cancer cell
lines (DLD-1 cells, WirDr cells) were cultured in the presence of SCFA (butyric
acid, isobutyric acid, acetic acid) in order to evaluate the cell growth
inhibitory activity of SCFA (WST-8 assay) by calculating the IC50 value from the
dose-response curve. Results: Intake of BB536-y increased the total amount of
SCFA in the feces and significantly suppressed the detection rate of ETBF and
growth of putrefactive bacteria. Intake of BB536-y with FOS was associated with a
higher Bifidobacterium detection rate than that of BB536-y alone. The contents of
butyric acid, isobutyric acid, and acetic acid, namely, of SCFA, were also
decreased. Analysis of the results of culture of DLD-1 cells and WirDr cells in
the presence of butyric acid, isobutyric acid, and acetic acid revealed that each
of the substances showed significant cell growth-inhibitory activity, with the
activity being the highest for butyric acid, followed by that for isobutyric acid
and acetic acid. Conclusion: These findings suggest that intake of both BB536-y
and BB536-y with FOS prevents colorectal carcinogenesis.How to cite this article:
Ohara T, Suzutani T. Intake of Bifidobacterium longum and Fructo-oligosaccharides
prevents Colorectal Carcinogenesis. Euroasian J Hepato-Gastroenterol 2018;8(1):11
17.
PMID- 29963456
TI - Screening of Esophageal Varices by Noninvasive Means in Chronic Liver Disease.
AB - Introduction: Noninvasive assessment of esophageal varices (EV) decreases the
medical and financial burden related to screening and helps in the management of
patients with chronic liver diseases (CLDs). In this study, our aim was to assess
the utility of the platelet count/spleen diameter index for the noninvasive
evaluation of EV. Materials and methods: In this cross-sectional observational
study, a total of 100 CLD patients underwent screening endoscopy for EV in
Medicine and Gastroenterology Department, Sylhet MAG Osmani Medical College
Hospital, Sylhet, Bangladesh. Platelet count/spleen diameter ratio was assessed
in all patients and its diagnostic implication was calculated. Results: Upper
gastrointestinal endoscopy revealed that 45 (45.0%) patients had medium EV
followed by 27 (27.0%) that had small EV and 19 (19.0%) patients had large EV.
Receiver operator characteristic (ROC) curve was constructed using platelet
count/spleen index, which gave a cut-off value of >905. The validity of platelet
count/spleen index evaluation of CLD was: Sensitivity 92.3%, specificity 66.7%,
accuracy 90.0%, positive predictive value (PPV) and negative predictive value
(NPV) were 96.6 and 46.2% respectively. True positive was 84 cases, false
positive 3 cases, false negative 7 cases, and true negative 6 cases. If we
consider cut-off value as 909 in the evaluation of EV in CLD, then true positive
was 85 cases, false positive 3 cases, false negative 6 cases, and true negative 6
cases. From this, by calculation, sensitivity was 93.4%, specificity 66.7%,
accuracy 91%, PPV 96.6%, and NPV 50%. Conclusion: The platelet count/spleen index
may be proposed to be a safe and reliable mean of screening of EV in CLD
patients; however, case-control study would be required to validate this.How to
cite this article: Hossain E, Ahammed F, Saha SK, Foez SA, Rahim MA, Noor-e-Alam
SM, Abdullah AS. Screening of Esophageal Varices by Noninvasive Means in Chronic
Liver Disease. Euroasian J Hepato-Gastroenterol 2018;8(1):18-22.
PMID- 29963457
TI - Diagnostic and Prognostic Role of Serum Interleukin-6 in Malignant Transformation
of Liver Cirrhosis.
AB - Aim: Alpha-fetoprotein (AFP) is still the most commonly used and the single most
recommended marker in the diagnosis of hepatocellular carcinoma (HCC).
Interleukin (IL)-6 is a circular cytokine and its role on carcinogenesis in
various hematological and solid tumors is clearly documented. A combination of
serum IL-6 and AFP may provide beneficial information regarding early diagnosis
of HCC. In this study, the effect of plasma IL-6 level in the diagnosis of HCC
was investigated. Materials and methods: A total of 130 patients with liver
cirrhosis, together with 30 control cases were enrolled in the trial. A diagnosis
of HCC was present in 75 patients (57.6%) in the liver cirrhosis group. Blood
samples were obtained from the enrolled study and control cases. Alpha
fetoprotein was quantified by chemiluminescent method. Plasma IL-6 levels of
samples obtained at -80 degrees C were quantified by human IL-6 BMS213/2
BMS213/2TEN kit. Results: The HCC patients were older than the patients in the
cirrhosis group (p = 0.016). On comparison of the HCC patients with the control
group, AFP (p < 0.001) and IL-6 (p < 0.001) were significantly higher among the
HCC patients. Comparison of HCC patients with liver cirrhosis cases with no
diagnosis of HCC revealed significantly high AFP (p < 0.001) and IL-6 levels (p <
0.001) in HCC group. Cutoff value for IL-6 was calculated as 5.73 (pg/mL). No
difference was detected in AFP (p = 0.600) and IL-6 (0.344) in all three
subgroups. A total of 17 patients died during a mean follow-up period of 32.9
months. No correlation was found between mean AFP values and IL-6 values and
survival rates. Conclusion: Plasma IL-6 level was found to be significant in the
diagnosis of HCC. Alpha-fetoprotein and IL-6 provided no advantage in terms of
early diagnosis of HCC and no correlation was observed between these markers and
survival.How to cite this article: Yakut M, Ozkan H, Karakaya MF, Erdal H.
Diagnostic and Prognostic Role of Serum Interleukin-6 in Malignant Transformation
of Liver Cirrhosis. Euroasian J Hepato-Gastroenterol 2018;8(1):23-30.
PMID- 29963458
TI - The Incidence and Predictive Factors in the Development of Acute Hepatitis in
Patients with Leukemia.
AB - Introduction: Liver involvement is common in hematological malignancies, but the
incidence and pattern of liver injury vary among the different types. The aims of
our study were to determine the incidence and clinical course of acute hepatitis
and the important factors for its development in patients with leukemia after
chemotherapy. Materials and methods: All patients with the diagnosis of leukemia
who were treated at the Department of Hematology between January 2008 and January
2013 were included in the study. A detailed medical history, clinical and
laboratory findings, treatment modalities, complications, and clinical course
were recorded retrospectively. Results: A total of 124 patients (64 females) with
the diagnosis of leukemia were included in the study. The mean age was 45.2 years
(16-89 years) and mean follow-up time was 29.7 months (0.25-192 months). A total
of 43 (34.6%) patients had acute hepatitis after chemotherapy. Pattern of liver
injury was hepatocellular in 31 patients, cholestasis in 2, and mix in 10
patients. Age (p = 0.001), hepatitis B surface antigen (HBsAg, p = 0.007), acute
leukemia (p < 0.001), positive blood culture (p = 0.004), the amount of
transfused red blood cell (p = 0.001), and amount of transfused platelets (p =
0.002) were significantly different under univariate analysis between the acute
hepatitis group and the nonacute hepatitis group. Under multivariate analysis,
only acute lymphoblastic leukemia (ALL) was identified as independent predictive
factor for development of acute hepatitis after starting chemotherapy.
Conclusion: Acute and self-limited hepatitis develops in the substantial
proportion of patients with leukemia. The most important factor for development
of acute hepatitis is the type of leukemia.How to cite this article: Kaya M,
Akdogan R, Ucmak F, Ayyildiz MO, Karakus A, Kaplan MA. The Incidence and
Predictive Factors in the Development of Acute Hepatitis in Patients with
Leukemia. Euroasian J Hepato-Gastroenterol 2018;8(1):31-37.
PMID- 29963459
TI - Cross-validation Studies of a Novel Low-cost Hepatitis B Virus Quantitative
Polymerase Chain Reaction System.
AB - Aim: This research focused on the results of the cross-validation program related
with the performance of a Cuban novel low-cost real-time quantitative polymerase
chain reaction (qPCR) assay for hepatitis B virus (HBV) quantification developed
by the Therapeutic Vaccine against Hepatitis B Department, Vaccines Division,
Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba. Materials
and methods: Dilution series with the plasmid standard at concentrations of
900,000 to 0.09 copies/reaction (c/r) were made for each PCR instrument. The mean
cycles threshold (Ct) values and PCR efficiency were compared among the cyclers.
Hepatitis B virus-positive serum samples were used for the calculation of
reproducibility of the HBV assay. Biotecon Diagnostics (BCD) also ordered the
oligo sequences from a second supplier and compared the PCR performance to those
provided from the CIGB. Results: All PCR cyclers were able to detect
concentrations up to 0.09 c/r. However, below the concentration of 9 c/r, the
variation of results increased within and between the cyclers. The PCR efficiency
showed satisfying results. The overall coefficient of variation (CV) cycler
values were 1.29 and 0.91% for M6 and M19 respectively. No significance was
observed between the different primer suppliers. Conclusion: The HBV assay was
performed with a good concordance between the five real-time instruments from
different suppliers. The HBV assay was also performed with a high reproducibility
for samples with a high and a low viral load. The HBV assay is robust against
different primer suppliers.How to cite this article: Aguiar J, Silva JA, Garcia
G, Guillen G, Aguilar JC. Cross-validation Studies of a Novel Low-cost Hepatitis
B Virus Quantitative Polymerase Chain Reaction System. Euroasian J Hepato
Gastroenterol 2018;8(1):38-41.
PMID- 29963460
TI - Nature of Host Immunity during Hepatitis B Virus Infection and designing Immune
Therapy.
AB - Hepatitis B virus (HBV) infections represent one of the major public health
problems in global context. More than 2 billion people in the world have been
infected with this virus at some point of time in their life and millions are
chronically infected, indicating that chronic HBV-infected subjects remain as a
living source of HBV transmission. The public health impact of this is
tremendous. Considerable numbers of chronic HBV-infected individuals would
eventually develop progressive liver diseases and their complications like
hepatic failure, liver cirrhosis (LC), and hepatocellular carcinoma (HCC).
Epidemiological studies have suggested that about 0.6 to 1.2 million people die
annually from HBV-related liver diseases. These figures about death due to HBV
and sufferings from HBV-related diseases indicate a notion of medical emergencies
about HBV. In addition to these, the impact of HBV on health care delivery system
moves beyond these numbers of HBV-related patients and HB-related deaths. This is
because significant insights have already been developed about epidemiology,
virology, and pathogenesis of HBV. Also, an effective and widely used preventive
vaccine is available against HBV. In addition to these, antiviral drugs against
HBV have been developed from early 1980s and several such drugs are now available
commercially in the open market around the worldwide. Unfortunately, the ongoing
therapeutic regimens could not stand the test of time and new insights about HBV
pathogenesis are required for the development of new, novel, and evidence-based
therapies for chronic HBV infections. How to cite this article: Akbar SMF, Al
Mahtab M, Khan SI. Nature of Host Immunity during Hepatitis B Virus Infection and
designing Immune Therapy. Euroasian J Hepato-Gastroenterol 2018;8(1):42-46.
PMID- 29963461
TI - Nonalcoholic Fatty Liver Disease: Time to Take the Bull by the Horns.
AB - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease
in the world affecting almost one-fourth of the population. It may progress to
nonalcoholic steatohepatitis (NASH), cirrhosis, end-stage liver disease, and
liver cancer in the long run. Besides, it may make the natural history in other
chronic liver diseases worse too. Furthermore, patients of NAFLD more often
suffer from metabolic syndrome, ischemic heart disease, and extrahepatic
malignancies than others, leading to a lower overall survival than the general
population. Obesity and sedentary lifestyle are among the most important risk
factors for NAFLD apart from increasing age, male sex, and certain genetic
factors. Due to the rising incidence, possible adverse consequences, and the
futile available treatment options, prevention is the key to tackle this health
menace. Spreading awareness, adopting a healthy lifestyle with appropriate
dietary modifications, regular physical activity are the cornerstones for
challenging this unfolding monster. How to cite this article: Nath P, Singh SP.
Nonalcoholic Fatty Liver Disease: Time to Take the Bull by the Horns. Euroasian J
Hepato-Gastroenterol 2018;8(1):47-51.
PMID- 29963462
TI - Management of Hepatocellular Carcinoma: Bangladesh Perspective.
AB - Bangladesh is one of the countries facing huge burden of hepatocellular carcinoma
(HCC). Hepatocellular carcinoma is the third commonest cancer in the country and
it is just behind to cancer of the lung and cancer of the stomach. Hepatitis B
virus (HBV) is responsible for 66% of HCC in Bangladesh. Presumptive prevalence
of HBV and hepatitis C virus (HCV) may be as high as 5.4 and 0.84%, respectively,
in Bangladesh, and liver diseases occupied 8 to 12% of admission in medicine
wards of Public Medical College. In this mini review, I would like to highlight
the impact of HBV and HCV in the development of HCC and the management of HCC
from a Bangladesh perspective. How to cite this article: Noor-E-Alam SM.
Management of Hepatocellular Carcinoma: Bangladesh Perspective. Euroasian J
Hepato-Gastroenterol 2018;8(1):52-53.
PMID- 29963463
TI - Hepatocellular Carcinoma in Malaysia and Its Changing Trend.
AB - Hepatocellular carcinoma (HCC) is one of the leading causes of death globally. In
Malaysia liver cancer is the eighth most common cause of cancer for both gender
and fifth most common cause of cancer for males. Liver cancer is a cause of
premature death in Malaysia: The trend from 1990 to 2010 was observed upward.
Since 1990, the annual years of life lost (YLLs) from liver cancer have increased
by 31.5%. Older persons are at higher risk and there is male predominance
observed. Curative surgical resection, liver transplantation, and supportive
symptomatic care, including percutaneous ethanol injection and radiofrequency
ablation (RFA), and noncurative transarterial chemoembolization (TACE) are among
available treatment facilities. Yet the survival rate is very poor as majority of
patients present at very advanced stage. Hepatitis B virus (HBV) remained the
leading cause of HCC in Malaysia. Several studies showed cryptogenic causes,
which are mainly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic
steatohepatitis (NASH) among the predominant causes of HCC in Malaysia than
hepatitis C virus (HCV), alcohol, or any other reason. This mainly correlates
with the increasing incidence of diabetes and obesity in Malaysia. How to cite
this article: Raihan R, Azzeri A, Shabaruddin FH, Mohamed R. Hepatocellular
Carcinoma in Malaysia and Its Changing Trend. Euroasian J Hepato-Gastroenterol
2018;8(1):54-56.
PMID- 29963464
TI - Epidemiology, Genotype Distribution, Prognosis, Control, and Management of Viral
Hepatitis B, C, D, and Hepatocellular Carcinoma in Mongolia.
AB - Mongolia is located between Russia and China. The total population of Mongolia as
of December 2017 is estimated to be 3.2 million people. According to our previous
study results, the prevalence of HBV was 11.8%, and anti-HDV was detected in 4.8%
among the HBsAg-positive subjects. Interestingly, most HCV infection is caused by
genotype 1b. Among all HBV DNA-positive samples, 98.5% were classified into
genotype D, and regarding HDV genotypes, all HDV RNA-positive samples, 100%, were
classified into genotype I. The second study is the baseline survey of a
Nationwide Cancer Cohort Study. Prevalence of HBsAg was 10.6%. Additionally, HCV
infection was observed in 9.9%, and 0.8% were coinfected with HBV and HCV among
the general population aged from 10 to 64 years. The third study investigated the
population-based prevalence of hepatitis B and C virus in apparently healthy
population of Ulaanbaatar city, Mongolia. The anti-HCV prevalence was 9.0%. In
addition, the prevalence of HBV was 8.0%. The fourth study is on the prevalence
of HCV and coinfections among nurses in a tertiary hospital in Mongolia. The
prevalence of HCV was 18.9%. Additionally, HBV infection was observed in 23.1%,
and 1.2% were coinfected with HCV and HBV. Mongolia has the highest HCC incidence
in the world (78.1/100,000, 3.5* higher than China). As a result, the Mongolia
government has launched The National Viral Hepatitis Program, which is a
comprehensive program that involves all aspects from prevention to care and
disease control to meet a reduction goal for morbidity and mortality due to HBV,
HCV, and HDV. Consequently, access to antiviral therapies is now improving in
Mongolia. How to cite this article: Baatarkhuu O, Gerelchimeg T, Munkh-Orshikh D,
Batsukh B, Sarangua G, Amarsanaa J. Epidemiology, Genotype Distribution,
Prognosis, Control, and Management of Viral Hepatitis B, C, D, and Hepatocellular
Carcinoma in Mongolia. Euroasian J Hepato-Gastroenterol 2018;8(1):57-62.
PMID- 29963465
TI - Liver Cancer in Nepal.
AB - Hepatocellular carcinoma (HCC) is highly incidental in South Asian countries.
Nepal, however, has low incidence for HCC owing to low prevalence for hepatitis B
virus (HBV) and hepatitis C virus (HCV) infections. Nepal lacked national cancer
registry until 2003. Though there has been some effort in having one, the current
registry incorporates twelve centers and may not properly represent the total
cancer burden in the country. Serology for HBV and HCV is seen to be positive in
nearly 25 to 30% and 5 to 10% of HCCs respectively. Clinical characteristics of
HCCs in Nepal have been discussed in this mini-review and it features poor
performance status and advanced stage at presentation, making only a small
fraction of these subjects eligible for curative treatment options. Most of the
standard treatment modalities are available in Nepal and appear to be reasonably
affordable as compared with other developed nations. How to cite this article:
Shrestha A. Liver Cancer in Nepal. Euroasian J Hepato-Gastroenterol 2018;8(1):63
65.
PMID- 29963466
TI - Liver Disease in Singapore.
AB - Liver disease is a significant health issue in Singapore. In the Singapore Burden
of Disease Survey, liver cancer and liver cirrhosis contributed 3.2 and 0.9% of
years of life lost (YLL) out of 182,753 YLL respectively. Liver cancer was ranked
8th and liver cirrhosis was ranked 20th in YLL. Liver cancer is the 5th most
common cancer in males, and has an age-adjusted rate of 17.6 per 100,000
population. The underlying etiology of liver cirrhosis is chronic hepatitis B
(CHB) in 63.3%, alcohol in 11.2%, cryptogenic in 9%, and chronic hepatitis C
(CHC) in 6.9%. The overall seroprevalence rate of CHB is 3.6%, while CHC is
approximately 0.1%. The trend in prevalence of liver cancer is gradually reducing
as is CHB. However, less is known about alcoholic liver disease and fatty liver
disease and there is some evidence that the latter is increasing. Singapore has a
multilayered health care system designed to provide basic health care needs to
the population. There are various schemes available that provide subsidized and
assisted health care for treatment of hepatitis B and C as well as liver
transplantation. Health policy with regard to a national action plan has not yet
been developed and there is room for health care specialists, government and
nongovernment agencies to work together to tackle liver disease in Singapore. How
to cite this article: Muthiah M, Chong CH, Lim SG. Liver Disease in Singapore.
Euroasian J Hepato-Gastroenterol 2018;8(1):66-68.
PMID- 29963467
TI - Nonalcoholic Fatty Liver Disease: Identifying the Disease Burden in Sri Lanka.
AB - Nonalcoholic fatty liver disease (NAFLD) is becoming one of the most important
causes for chronic liver disease and also hepatocellular carcinoma (HCC) in Sri
Lanka. This tendency is also recognized worldwide. More than half of the middle
aged and elderly adults in urban Sri Lanka have ultrasonic evidence of NAFLD. The
NAFLD is also identified in population from rural areas of Sri Lanka and also in
children. Nonalcoholic steatohepatitis (NASH) cirrhosis is the most common cause
of referral for liver transplantation in Sri Lankans. The NASH is also the most
common cause for rejecting potential donors for liver transplantation in Sri
Lanka. Patients who underwent liver transplantation for cryptogenic cirrhosis
developed evidence of NASH following liver transplantation. Recent evidence
suggests that there is a genetic component to NAFLD. PNPLA3, a single gene
polymorphism linked to the short arm of chromosome 22, is associated with the
severity of NAFLD. The presence of this genetic polymorphism appears to carry
higher risk of patients with NAFLD developing NASH with fibrosis cirrhosis and
hepatocellular carcinoma. In a large population-based study from Sri Lanka, there
was a tendency to develop NAFLD associated with this genetic polymorphism. In a
population-based study, NAFLD was identified as an independent risk factor for
development of diabetes. This association is recognized worldwide now. Most
patients with HHC in Sri Lanka developed it on a back ground of cryptogenic
cirrhosis. At the same time, the prevalence of the markers for hepatitis B and C
was rare in Sri Lankan patients with HCC. How to cite this article: Dassanayake
AS. Nonalcoholic Fatty Liver Disease: Identifying the Disease Burden in Sri
Lanka. Euroasian J Hepato-Gastroenterol 2018;8(1):69-72.
PMID- 29963468
TI - Epidemiology of Chronic Hepatitis B in Turkey.
AB - Hepatitis B virus (HBV) infection is a global public health problem and it is
also a major health concern of Turkey. The estimated number of HBV carriers in
Turkey is about 3.3 million, with an overall HBV prevalence of 4.57%. Thus, both
prevention and therapy of HBV-infected patients are urgent medical need of
Turkey. A total of 1,533 among 37,637 patients who were examined at the
Department of Gastroenterology, Ankara University School of Medicine were found
to be hepatitis B surface antigen (HBsAg) positive (4%). Viral hepatitis
treatment is fully reimbursed in Turkey through the national insurance system,
which covers all residents across Turkey. How to cite this article: Ozkan H.
Epidemiology of Chronic Hepatitis B in Turkey. Euroasian J Hepato-Gastroenterol
2018;8(1):73-74.
PMID- 29963469
TI - Reviewing of Research Finding of Hepatitis B Virus Infection in Lao People's
Democratic Republic.
AB - The seroprevalence of hepatitis B virus (HBV) surface antigen (HBsAg)-positive
blood donors was 8.7%. The prevalence among males (9.7%) was higher than among
females (6.2%). The prevalence of antihepatitis C virus (HCV)-positive blood
donors was 1.1%, with no significant differences between males (1.1%) and females
(1.0%). Annual positive rates for HBsAg and anti-HCV donors during the years 2003
to 2005 did not differ significantly. In Lao People's Democratic Republic (PDR),
HBV is highly endemic. However, blood donations are only screened for HBsAg,
leaving a risk of transmission by HBsAg-negative occult infected donors. Here, we
characterized first-time blood donors to assess prevalence of HBV infections and
occult infected donors. Despite hepatitis B vaccination at birth and at 6, 10,
and 14 weeks of age, HBV infection continues to be endemic in Lao PDR. We carried
a cross-sectional serological study in infants, preschool children, school
pupils, and pregnant women to determine their burden of disease, risk of
infection, and vaccination status. The prevalence of HBsAg carriage in pregnant
women is a relevant marker for the risk of mother-to-child HBV transmission. This
study aimed to assess the changes in prevalence of HBV infection among pregnant
women attending Mahosot Prenatal Clinic (Vientiane). How to cite this article:
Ounavong A. Reviewing of Research Finding of Hepatitis B Virus Infection in Lao
People's Democratic Republic. Euroasian J Hepato-Gastroenterol 2018;8(1):75-76.
PMID- 29963470
TI - Changing Etiology in Liver Cirrhosis in Sapporo, Japan.
AB - In Japan, preventive measures and antiviral therapy against acute or chronic
viral infection had achieved remarkable progress in the 1980s or later. On the
contrary, metabolic syndrome complicated with fatty liver has emerged as a public
health concern to date. In the current study, we attempted to clarify etiological
changes in liver cirrhosis treated in a single tertiary institute in Sapporo,
Japan, from 1998 to 2016. Medical records of 1,166 patients (787 males, with mean
of 64.9 +/- 11.7 years), diagnosed as having liver cirrhosis for 19 years, were
retrospectively reviewed to analyze etiology and clinical features. During the
past 10 years, annual numbers of cirrhotic patients with chronic infection of
hepatitis B virus (HBV) or hepatitis C virus (HCV) decreased from 50 or more to
20 or less, and alcoholic liver disease or cryptogenic liver injury emerged as
major cause of liver cirrhosis. Among 100 cirrhotic patients of unknown cause,
nonalcoholic fatty liver disease (NAFLD) occupied almost 50% in 19 observational
years. In order to control the rising trend in NAFLD related with metabolic
syndrome, preventive measures including education in society would be required in
Japan. How to cite this article: Kang J-H, Matsui T. Changing Etiology in Liver
Cirrhosis in Sapporo, Japan. Euroasian J Hepato-Gastroenterol 2018;8(1):77-80.
PMID- 29963471
TI - Burden of Alcoholic Liver Disease: Bhutan Scenario.
AB - Alcoholic liver disease (ALD) is one of the major public health problems in
Bhutan. The incidence of alcohol liver diseases (per 10,000 populations) in the
year 2016 was 46. The burden of mortality associated with it is alarming, going
by the size of the population of the country. It is one of the all-time top five
killer diseases in the country. In 2016, the mortality attributable to alcohol
liver disease was 184 corresponding to 97% of deaths due to reported liver
diseases. The ALD is responsible for 15% of all deaths on an average in the last
3 years. How to cite this article: Wangchuk P. Burden of Alcoholic Liver Disease:
Bhutan Scenario. Euroasian J Hepato-Gastroenterol 2018;8(1):81-82.
PMID- 29963472
TI - Hepatocellular Carcinoma Surveillance: Benefit of Serum Alfa-fetoprotein in Real
world Practice.
AB - Introduction: Better treatment outcome of early-stage hepatocellular carcinoma
(HCC) warrants employment of screening programs, in which ultrasonography (US)
and serum alfa-fetoprotein (AFP) have been recommended. Considering cost
effectiveness, serum AFP has recently been withdrawn from several guidelines for
HCC surveillance. However, there were limited studies on benefits of AFP for HCC
surveillance in Thailand. Materials and methods: This is a retrospective study of
a proportion of HCC cases in which a diagnostic study was triggered by high serum
AFP levels, but US failed to detect the lesion. Patients who received diagnostic
imaging for HCC at Siriraj Hospital between January 1, 2012 and December 31, 2014
were included. All the patients must fulfill criteria for HCC surveillance
according to American Association for the Study of Liver Diseases (AASLD)
practice guidelines on the management of HCC 2010 or European Association for the
Study of the Liver-European Organisation for Research and Treatment of Cancer
(EASL-EORTC) Clinical Practice Guidelines: Management of HCC 2012. Previous
diagnosis of any liver malignancy was excluded. Demographic data, underlying
liver diseases, screening of AFP and US results, and definite diagnosis of HCC
were recorded. Results: Of the 452 cases who fulfilled inclusion and exclusion
criteria, chronic hepatitis B, C, and alcoholic cirrhosis were accountable for
53.8, 25.9, and 7.3% respectively. Totally, 150 cases were diagnosed with HCC.
Additional HCC detection rate by high serum AFP but failed US of 15.3% was
demonstrated. Subgroup analysis revealed significant benefit of AFP in cirrhotic
patients with chronic hepatitis B and C (p-value 0.004 and 0.002). No significant
benefit was observed in cirrhosis of other causes and in noncirrhotic chronic
hepatitis B. Conclusion: We reported a 15.3% additional benefit of serum AFP for
HCC surveillance in conjunction with US of liver. Chronic hepatitis B and C with
cirrhosis significantly derived the benefit from serum AFP screening.How to cite
this article: Lersritwimanmaen P, Nimanong S. Hepatocellular Carcinoma
Surveillance: Benefit of Serum Alfa-fetoprotein in Real-world Practice. Euroasian
J Hepato-Gastroenterol 2018;8(1):83-87.
PMID- 29963473
TI - Hepatitis B Virus Infection among Health Care Workers in Indonesia.
AB - Hepatitis B virus (HBV) infection is a global health problem with an estimated
257 million chronically infected people. Indonesia is a moderately hepatitis B
endemic country with 7.1% prevalence of hepatitis surface antigen (HBsAg). This
infection is considered as an important occupational hazard among health care
workers (HCWs), who may become further transmitters of this infection. The extent
of hepatitis B among HCWs and specific control strategy are not available in
Indonesia. A study was done on 644 HCWs, who were categorized into
administration, nonintervention, and intervention groups. The prevalence of
HBsAg, antibody to HBV core antigen (anti-HBc), and antibody to HBsAg (anti-HBs)
was 4.7, 18.5, and 36.7% respectively, while 57.3% were negative for all
seromarkers, indicating susceptibility to this infection. Increasing trend with
age was observed in the exposure to infection (anti-HBc) (p <0.001) and the
marker of resolved infection (HBsAg-, anti-HBc+, anti-HBs+) (p = 0.004),
suggesting accumulated exposure to HBV infection by increasing age. Rising trend
of exposure rate was also observed across the administration, nonintervention,
and intervention groups (p < 0.001). By length of service period, significant
escalation of exposure (p = 0.010) and resolved infection (p < 0.001) were also
observed, suggesting increasing occupational risk to HBV infection. There is an
urgent need to safeguard the HCWs with hepatitis B vaccination and provide
continuing education at various health care setups. The establishment of a
national policy and a roadmap for effective and efficient intervention is
required for the prevention, diagnosis, postexposure management, and treatment of
HBV infection in this special population. How to cite this article: Muljono DH,
Wijayadi T, Sjahril R. Hepatitis B Virus Infection among Health Care Workers in
Indonesia. Euroasian J Hepato-Gastroenterol 2018;8(1):88-92.
PMID- 29963474
TI - F-18 Fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography
Findings of Isolated Gastric Tuberculosis mimicking Gastric Cancer and Lymphoma.
AB - Introduction: Tuberculosis (TB) infection is still a challenging health issue,
especially in developing countries. Diagnosing extrapulmonary infections,
especially isolated organ involvement, is difficult in most cases even with the
radiological, endoscopic, and histopathological examinations done for accurate
diagnosis. Here we describe a case of isolated gastric TB with specific F-18
fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography
(CT) findings mimicking gastric cancer/ lymphoma. Case report: A 20-year-old male
patient was admitted to our hospital with abdominal pain in the epigastric
region, weight loss, and fever especially at nights for 2 months. Physical
examination was normal. Hemoglobin was 9.6 gm/dL; the patient had iron deficiency
anemia. Upper gastrointestinal (GI) endoscopy was suggestive of gastric ulcer
mimicking malignancy. F-18 FDG PET/CT revealed multiple hypermetabolic malignant
lymphadenopathies in the abdomen and diffuse gastric wall thickening as linitis
plastica and multiple hypermetabolic peritoneal implants in the omentum.
Exploratory laparotomy was done for tissue diagnosis and exploration of the
peritoneum for TB infection, lymphoma, and Crohn's disease to make differential
diagnosis. Histopathology revealed granulomatous lymphadenitis with granulomas
including giant cells, suspecting TB. Patient was put on antituberculosis
treatment (ATT). After treatment, the complaints resolved, and he gained weight.
Fusion PET/CT exhibited a complete response to ATT with no residual disease.
Conclusion: According to our knowledge, this is the first report about F-18 FDG
PET/CT findings in the diagnosis of isolated gastric TB. F-18 FDG PET/CT may
provide help in the diagnosis and follow-up of isolated gastric TB in challenging
cases.How to cite this article: Akdogan RA, Rakici H, Gungor S, Bedir R, Akdogan
E. F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Findings of Isolated Gastric Tuberculosis mimicking Gastric Cancer and Lymphoma.
Euroasian J Hepato-Gastroenterol 2018;8(1):93-96.
PMID- 29963475
TI - Trichobezoar: Ravenous for Hair.
AB - : Trichophagia is the habit of chewing hair. On an average, only 1% patients with
trichophagia develop trichobezoar. They are usually symptomless until they reach
a large size. It is common in young females usually with an underlying
psychiatric disorder. The gold standard for diagnosis is upper gastrointestinal
endoscopy (UGIE). Here we present a case of trichobezoar in an 11-year-old girl
who presented in the emergency with complaint of pain abdomen and symptoms of
obstruction. Key messages: A high index of suspicion among physician can lead to
early diagnosis and management in these cases (trichobezoar).How to cite this
article: Prasad A, Jain A, Gupta A, Kamra A. Trichobezoar: Ravenous for Hair.
Euroasian J Hepato-Gastroenterol 2018;8(1):97-98.
PMID- 29963476
TI - Postobstructive Cyst Formation in Pancreatic Duct affecting Surgical Approach.
AB - How to cite this article: Ezer A, Parlakgumus A. Postobstructive Cyst Formation
in Pancreatic Duct affecting Surgical Approach. Euroasian J Hepato-Gastroenterol
2018;8(1):99-100.
PMID- 29963477
TI - The Journal in the Horizon of Asia and Europe.
PMID- 29963478
TI - Comparison of conventional imaging techniques and CBCT for periodontal
evaluation: A systematic review.
AB - Purpose: This study aimed to carry out a systematic review of studies in the
literature comparing conventional imaging techniques with cone-beam computed
tomography in terms of the role of these techniques for assessing any of the
following periodontal conditions and parameters: infrabony defects, furcation
involvement, height of the alveolar bone crest, and the periodontal ligament
space. Materials and Methods: Interventional and observational studies comparing
conventional imaging techniques with cone-beam computed tomography were
considered eligible for inclusion. The MEDLINE and Embase databases were searched
for articles published through 2017. The PRISMA statement was followed during
data assessment and extraction. Results: The search strategy yielded 351
publications. An initial screening of the publications was performed using
abstracts and key words, and after the application of exclusion criteria, 13
studies were finally identified as eligible for review. Conclusion: These studies
revealed cone-beam computed tomography to be the best imaging technique to assess
infrabony defects, furcation lesions, the height of the alveolar bone crest, and
the periodontal ligament space.
PMID- 29963479
TI - Accuracy of various imaging methods for detecting misfit at the tooth-restoration
interface in posterior teeth.
AB - Purpose: The present study aimed to evaluate which of the following imaging
methods best assessed misfit at the tooth-restoration interface: (1) bitewing
radiographs, both conventional and digital, performed using a photostimulable
phosphor plate (PSP) and a charge-coupled device (CCD) system; (2) panoramic
radiographs, both conventional and digital; and (3) cone-beam computed tomography
(CBCT). Materials and Methods: Forty healthy human molars with class I cavities
were selected and divided into 4 groups according to the restoration that was
applied: composite resin, composite resin with liner material to simulate misfit,
dental amalgam, and dental amalgam with liner material to simulate misfit.
Radiography and tomography were performed using the various imaging methods, and
the resulting images were analyzed by 2 calibrated radiologists. The true
presence or absence of misfit corresponding to an area of radiolucency in regions
subjacent to the esthetic and metal restorations was validated with microscopy.
The data were analyzed using a receiver operating characteristic (ROC) curve, and
the scores were compared using the Cohen kappa coefficient. Results: For bitewing
images, the digital systems (CCD and PSP) showed a higher area under the ROC
curve (AUROC) for the evaluation of resin restorations, while the conventional
images exhibited a larger AUROC for the evaluation of amalgam restorations.
Conventional and digital panoramic radiographs did not yield good results for the
evaluation of resin and amalgam restorations (P<.05). CBCT images exhibited good
results for resin restorations (P>.05), but showed no discriminatory ability for
amalgam restorations (P<.05). Conclusion: Bitewing radiographs (conventional or
digital) should be the method of choice when assessing dental restoration misfit.
PMID- 29963480
TI - Radiopacity of contemporary luting cements using conventional and digital
radiography.
AB - Purpose: This study evaluated the radiopacity of contemporary luting cements
using conventional and digital radiography. Materials and Methods: Disc specimens
(N=24, n=6 per group, o7 mm*1 mm) were prepared using 4 resin-based luting
cements (Duolink, Multilink N, Panavia F 2.0, and U-cem). The specimens were
radiographed using films, a complementary metal oxide semiconductor (CMOS)
sensor, and a photostimulable phosphor plate (PSP) with a 10-step aluminum step
wedge (1 mm incremental steps) and a 1-mm-thick tooth cut. The settings were 70
kVp, 4 mA, and 30 cm, with an exposure time of 0.2 s for the films and 0.1 s for
the CMOS sensor and PSP. The films were scanned using a scanner. The radiopacity
of the luting cements and tooth was measured using a densitometer for the film
and NIH ImageJ software for the images obtained from the CMOS sensor, PSP, and
scanned films. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U
tests. Results: Multilink (3.44-4.33) showed the highest radiopacity, followed by
U-cem (1.81-2.88), Panavia F 2.0 (1.51-2.69), and Duolink (1.48-2.59). The R2
values of the optical density of the aluminum step wedge were 0.9923 for the
films, 0.9989 for the PSP, 0.9986 for the scanned films, and 0.9266 for the CMOS
sensor in the linear regression models. Conclusion: The radiopacities of the
luting materials were greater than those of aluminum or dentin at the same
thickness. PSP is recommended as a detector for radiopacity measurements because
of its accuracy and convenience.
PMID- 29963481
TI - Uses of cone-beam computed tomography in San Jose, Costa Rica.
AB - Purpose: To analyze cone-beam computed tomography (CBCT) use, indications, and
exposure parameters in San Jose, Costa Rica. Materials and Methods: A cross
sectional study was performed. All CBCT examinations over a period of 6 months at
2 radiological centers in San Jose, Costa Rica were evaluated. The examinations
were performed with Veraview EPOC X550 and Veraviewepocs 3D R100 equipment. The
patients' age and sex, clinical indication for CBCT, region of interest (ROI),
repeat examinations, specialty of the referring dentist, field-of-view (FOV),
tube voltage (kV), tube current (mA), and radiation dose (uGy) were evaluated.
Patients were classified by age as children (<=12 years), adolescents (13-18
years), and adults (>=19 years). Results: The mean age of the 526 patients was
49.4 years. The main indications were implant dentistry and dental trauma. The
most frequent ROIs were posterior, while anterior ROIs were much less common. The
highest percentage of repeat examinations was in children. Fifty-six percent of
the referring dentists were specialists. The most commonly used FOV was small.
The mean tube voltage and current were 79.8 kV and 7.4 mA for Veraview EPOC X550
and 89.9 kV and 6 mA for Veraviewepocs 3D R100, respectively. The mean doses for
children, adolescents, and adults were 6.9 uGy, 8.4 uGy, and 7.8 uGy,
respectively. Conclusion: Although CBCT was most commonly used in adults for
implant dentistry, most repeat examinations were in children, and the highest
mean dose was in adolescents. Additional dose optimization efforts should be made
by introducing low-dose protocols for children and adolescents.
PMID- 29963482
TI - Linear accuracy of cone-beam computed tomography and a 3-dimensional facial
scanning system: An anthropomorphic phantom study.
AB - Purpose: This study was conducted to evaluate the accuracy of linear measurements
of 3-dimensional (3D) images generated by cone-beam computed tomography (CBCT)
and facial scanning systems, and to assess the effect of scanning parameters,
such as CBCT exposure settings, on image quality. Materials and Methods: CBCT and
facial scanning images of an anthropomorphic phantom showing 13 soft-tissue
anatomical landmarks were used in the study. The distances between the anatomical
landmarks on the phantom were measured to obtain a reference for evaluating the
accuracy of the 3D facial soft-tissue images. The distances between the 3D image
landmarks were measured using a 3D distance measurement tool. The effect of
scanning parameters on CBCT image quality was evaluated by visually comparing
images acquired under different exposure conditions, but at a constant threshold.
Results: Comparison of the repeated direct phantom and image-based measurements
revealed good reproducibility. There were no significant differences between the
direct phantom and image-based measurements of the CBCT surface volume-rendered
images. Five of the 15 measurements of the 3D facial scans were found to be
significantly different from their corresponding direct phantom measurements
(P<.05). The quality of the CBCT surface volume-rendered images acquired at a
constant threshold varied across different exposure conditions. Conclusion: These
results proved that existing 3D imaging techniques were satisfactorily accurate
for clinical applications, and that optimizing the variables that affected image
quality, such as the exposure parameters, was critical for image acquisition.
PMID- 29963483
TI - Is the diagnosis of calcified laryngeal cartilages on panoramic radiographs
possible?
AB - Purpose: Detecting laryngeal cartilages (triticeous and thyroid cartilages) on
panoramic radiographs is important because they may be confused with carotid
artery calcifications in the bifurcation region, which are a risk factor for
stroke. This study assessed the efficiency of panoramic radiography in the
diagnosis of calcified laryngeal cartilages using cone-beam computed tomography
(CBCT) as the reference standard. Materials and Methods: A total of 312 regions
(142 bilateral, 10 left, 18 right) in 170 patients (140 males, 30 females) were
examined. Panoramic radiographs were examined by an oral and maxillofacial
radiologist with 11 years of experience. CBCT scans were reviewed by 2 other oral
and maxillofacial radiologists. The kappa coefficient (kappa) was calculated to
determine the level of intra-observer agreement and to determine the level of
agreement between the 2 methods. Diagnostic indicators (sensitivity, specificity,
accuracy, and false positive and false negative rates) were also calculated. P
values <.05 were considered to indicate statistical significance. Results: Eighty
two images were re-examined to determine the intra-observer agreement level, and
the kappa coefficient was calculated as 0.709 (P<.05). Statistically significant
and acceptable agreement was found between the panoramic and CBCT images
(kappa=0.684 and P<.05). The sensitivity, specificity, diagnostic accuracy rate,
the false positive rate, and the false negative rate of the panoramic radiographs
were 85.4%, 83.5%, 84.6%, 16.5%, and 14.6%, respectively. Conclusion: In most
cases, calcified laryngeal cartilages could be diagnosed on panoramic
radiographs. However, due to variation in the calcifications, diagnosis may be
difficult.
PMID- 29963484
TI - Osseous metaplasia showing heterotopic ossification in the maxillary sinus.
AB - Radiopacity in the maxillary sinus can be observed in various conditions, such as
in the presence of lesions in the maxillary sinus or as a sequela of maxillary
sinus surgery. This report describes the case of a 57-year-old female patient who
had no previous history of surgical treatment or traumatic injury of the nose or
maxillary sinus. Both maxillary sinuses were indistinguishable on panoramic
radiography and showed signs of radiopacity. Computed tomography images revealed
that the maxillary sinuses were filled with bony tissue and exhibited signs of
sinus mucosal thickening. Biopsy results showed fragments of trabecular bone with
fibrous tissue.
PMID- 29963485
TI - Recurrent symptomatic cemento-osseous dysplasia: A case report.
AB - Cemento-osseous dysplasia (COD) is a benign fibro-osseous lesion of bone, in
which normal bone is replaced by fibrous tissue, followed by calcification with
osseous and cementum-like tissue. COD is classified into 3 categories according
to its location: periapical, focal, and florid COD (FCOD). On radiography, FCOD
appears radiolucent in its early stages. As it matures, radiopacities appear
within the lesion, causing them to show a mixed appearance of radiolucency and
radiopacity. Because FCOD is usually asymptomatic and grows in a self-limited
manner, it does not require treatment. Secondary infection is the most frequent
cause of symptomatic cases. We report a case of FCOD with symptoms that appeared
after a dental restoration procedure and persisted after repeated operations. The
purpose of this report is to emphasize the importance of thorough radiological
evaluations of patients with FCOD before treatment.
PMID- 29963486
TI - Maxillary sinus aspergilloma of odontogenic origin: Report of 2 cases with cone
beam computed tomographic findings and review of the literature.
AB - Aspergilloma of the maxillary sinus is considered rare in immunocompetent
patients, but a considerable increase has recently been seen in the incidence of
reported cases. Dental procedures involving the antral region are thought to
predispose individuals to this form of aspergillosis. Because aspergilloma shares
similar clinical features with other sinus pathologies, its diagnosis may be
delayed. Thus, an early diagnosis confirmed by a histopathological examination
plays a crucial role in the adequate management of aspergilloma. This article
provides a concise review of the reported cases of aspergilloma associated with
dental procedures and reports 2 new cases of aspergilloma in middle-aged female
patients, with a presentation of their cone-beam computed tomographic findings.
PMID- 29963487
TI - Temporomandibular joint synovial chondromatosis accompanying temporal bone
proliferation: A case report.
AB - Synovial chondromatosis is a rare metaplastic disease affecting the joints,
including the temporomandibular joint (TMJ). Since its symptoms are similar to
those of temporomandibular disorders, a careful differential diagnosis is
essential. A 50-year-old male patient was referred with the chief complaint of
pain and radiopaque masses around the left TMJ on panoramic radiography.
Clinically, pre-auricular swelling and resting pain was found, without limitation
of mouth opening. On cone-beam computed tomographic images, multiple calcified
nodules adjacent to the TMJ and bone proliferation with sclerosis at the
articular fossa and eminence were found. T2-weighted magnetic resonance images
showed multiple signal-void nodules with high signal effusion in the superior
joint space and thickened cortical bone at the articular fossa and eminence. The
calcified nodules were removed by surgical excision, but the hypertrophic
articular fossa and eminence remained. A histopathological examination confirmed
the diagnosis. The patient was followed up few months later without recurrence.
PMID- 29963488
TI - Dental stem cells as a cell source for tissue engineering.
PMID- 29963489
TI - Angiogenesis and the prevention of alveolar osteitis: a review study.
AB - Angiogenesis is one of the essential processes that occur during wound healing.
It is responsible for providing immunity as well as the regenerative cells,
nutrition, and oxygen needed for the healing of the alveolar socket following
tooth extraction. The inappropriate removal of formed blood clots causes the
undesirable phenomenon of alveolar osteitis (AO) or dry socket. In this review,
we aimed to investigate whether enhanced angiogenesis contributes to a more
effective prevention of AO. The potential pro- or anti-angiogenic activity of
different materials used for the treatment of AO were evaluated. An electronic
search was performed in the PubMed, MEDLINE, and EMBASE databases via OVID from
January 2000 to September 2016 using the keywords mentioned in the PubMed and
MeSH (Medical Subject Headings) terms regarding the role of angiogenesis in the
prevention of AO. Our initial search identified 408 articles using the keywords
indicated above, with 38 of them meeting the inclusion criteria set for this
review. Due to the undeniable role of angiogenesis in the socket healing process,
it is beneficial if strategies for preventing AO are directed toward more
proangiogenic materials and modalities.
PMID- 29963490
TI - Comparison of the efficacy of amoxicillin-clavulanic acid with metronidazole to
azithromycin with metronidazole after surgical removal of impacted lower third
molar to prevent infection.
AB - Objectives: The goal of the study was to investigate the clinical effects of
amoxicillin-clavulanic acid (500+125 mg) with metronidazole 400 mg administered
three times daily (Group I) versus azithromycin 500 mg administered once daily
and with metronidazole 400 mg three times daily (Group II) for the prevention of
postoperative infection following mandibular third molar surgical removal.
Materials and Methods: The study design was a single-center prospective study.
Patients who reported to the Department of Oral and Maxillofacial Surgery between
February 2015 and January 2017 for removal of mandibular third molar were
screened, and 108 patients were chosen. One surgeon carried out all procedures.
Patients were prescribed antibiotics until the two groups contained a similar
number of cases. Results: Our data showed that Group II had fewer incidences of
surgical site infection, but with no statistical significance. Conclusion:
Although both treatments are used routinely after removal of the mandibular third
molar, neither is significantly better than the other.
PMID- 29963491
TI - Retrospective clinical study of multiple keratocystic odontogenic tumors in non
syndromic patients.
AB - Objectives: A keratocystic odontogenic tumor (KOT) is a type of odontogenic tumor
that mainly occurs in the posterior mandible. Most KOTs appear as solitary
lesions; however, they sometimes occur as multiple cysts. This study analyzed the
clinical features of multiple KOTs. Materials and Methods: The participants were
diagnosed with KOT by biopsy with multiple surgical sites, and were patients at
the Pusan National University Hospital and the Pusan National University Dental
Hospital from January 1, 2005 to March 31, 2016. Charts, records, images and
other findings were reviewed. Results: A total of 31 operations were conducted in
17 patients. The mean patient age was 28.4+/-20.1 years. Multiple KOTs were found
to occur at a young age (P<0.01). The predominant sites were in the posterior
mandible (28.6%). Most cases of multiple lesions appeared in both the upper and
lower jaw, and 40.3% of lesions were associated with unerupted and impacted
teeth. The overall recurrence rate measured by operation site was 10.4% (8/77
sites). No patients were associated with nevoid basal cell carcinoma syndrome.
Conclusion: The pure recurrence rate was lower than estimated, but there was a
higher possibility of secondary lesions regardless of the previous operation
site; therefore, long-term follow-up is necessary.
PMID- 29963492
TI - Clinical experience in managing temporomandibular joint ankylosis: five-year
appraisal in a Nigerian subpopulation.
AB - Objectives: Temporomandibular joint ankylosis (TMJA) is a joint pathology caused
by bony and/or fibrous adhesion of the joint apparatus, resulting in partial or
total loss of function. Materials and Methods: This is a retrospective study
conducted between 2012 and 2016 in the northwest region of Nigeria. The data
retrieved includes gender, age, etiology of ankylosis, duration of ankylosis,
laterality of ankylosis, type of imaging technique, type of airway management,
types of incision, surgical procedure, mouth opening, interpositional materials
used, and complications. Results were presented as simple frequencies and
descriptive statistics. Results: Thirty-six patients with TMJA were evaluated
during the study period. There were 21 males (58.3%) and 15 females (41.7%),
yielding a male:female ratio of 1.4:1. The patients' age ranged from 5 to 33
years with mean+/-standard deviation (13.8+/-6.6 years). Thirty-five cases
(97.2%) were determined to be true/bony ankylosis, while only 1 case (2.8%) was
false/fibrous ankylosis. Most of the TMJA cases (16 cases, 44.4%) were secondary
to a fall. In our series, the most commonly utilized incision was the Bramley-Al
Kayat (15 cases, 41.7%). The mostly commonly performed procedures were
condylectomies and upper ramus ostectomies (12 cases each, 33.3%), while the most
commonly used interpositional material was temporalis fascia (14 cases, 38.9%).
The complications that developed included 4 cases (11.1%) of severe hemorrhage, 1
case (2.8%) of facial nerve palsy, and 1 case (2.8%) of re-ankylosis. Conclusion:
Plain radiographs, with their shortcomings, still have significant roles in
investigating TMJA. Aggressive postoperative physiotherapy for a minimum of 6
months is paramount for successful treatment.
PMID- 29963493
TI - Expression of collagenases (matrix metalloproteinase-1, 8, 13) and tissue
inhibitor of metalloproteinase-1 of retrodiscal tissue in temporomandibular joint
disorder patients.
AB - Objectives: The aim of this study was to reveal how collagenases (matrix
metalloproteinase [MMP]-1, 8, 13) and tissue inhibitor of metalloproteinase 1
(TIMP-1) are expressed in immunohistochemistry of retrodiscal tissue in
temporomandibular joint disorder patients. Materials and Methods: This study was
conducted on 39 patients who underwent discoplasty or discectomy.
Immunohistochemical staining was undertaken and expression levels of MMP-1, 8,
13, and TIMP-1 were evaluated. The status of internal derangement of disc,
osteoarthritis, and joint effusion were analyzed using magnetic resonance imaging
(MRI). Disc status observed during operation was also categorized. Results: The
more severe disc derangement was observed on MRI, the more increased expression
of MMPs and TIMP-1 appeared. Regarding MMP-13 expression, 86.7% of late-stage
disc displacement patients showed grade II or III. Expression level of MMPs or
TIMP was not statistically significant associated with joint effusion level. In
perforation and/or adhesion groups, all patients showed grade II or III
expression of MMP-13. Once perforation occurred, MMP-13 showed increased
expression with statistical significance. Conclusion: MMP-1 and MMP-13 expression
seem to be related to progression of osteoarthritis whereas MMP-8 does not seem
to have a specific role with regard to temporomandibular joint disorders. TIMP-1
is considered to be partly related to internal derangement rather than
osteoarthritis, but it is not significant.
PMID- 29963495
TI - Angioleiomyoma of the oral cavity: a case report and brief review of the
literature.
AB - This study presents a case of an oral angioleiomyoma along with its clinical
diagnostic approach and laboratory confirmation. The differential diagnosis,
especially from angioleiomyosarcoma, is also included. A 51-year-old patient
presented with a tumor-like lesion on his upper labial mucosa. The clinical
examination revealed a benign lesion that was surgically removed.
Histopathological and immunohistochemical examinations confirmed the diagnosis of
an oral angioleiomyoma. The post-surgical period was uneventful. No recurrence
had occurred after a year of follow-up surveillance. Oral angioleiomyoma is a
very rarely occurring oral lesion. Clinically, it may mimic some benign lesions,
including fibroma, pyogenic granuloma or minor salivary gland tumor. Surgical
excision is the treatment of choice. Histological and immunohistochemical
examination can confirm the diagnosis. The differential diagnosis is crucial to
rule out angioleiomyosarcoma.
PMID- 29963494
TI - Maxillofacial reconstruction with Medpor porous polyethylene implant: a case
series study.
AB - Objectives: The role of alloplastic materials in maxillofacial reconstruction is
still controversial. Determining the utility of porous, high-density,
polyethylene implants as a highly stable and flexible, porous alloplast, with
properties such as rapid vascularization and tissue ingrowth, is crucial in cases
of maxillofacial deformities and aesthetic surgery. Materials and Methods: Thirty
high-density porous polyethylene implants were implanted in 16 patients that had
been referred to a private office over a three-year period. These implants were
used for correcting congenital deformities, posttraumatic defects and improving
the aesthetic in nasal, paranasal, malar, chin, mandibular angle, body and
orbital areas. Results: The outcomes of the cases in this study showed good
aesthetic and functional results. The majority of patients had no signs of
discomfort, rejection or exposure. Two implants suffered complications: a
complicated malar implant was managed by antibiotic therapy, and an infected
mandibular angle implant was removed despite antibiotic therapy. Conclusion:
Based on the results, the Medpor implant seems to be an excellent biomaterial for
correcting various facial deformities. Advantages include its versatility and
relatively ideal pore size that allows for excellent soft tissue ingrowth and
coverage. It is strong, flexible and easy to shape.
PMID- 29963496
TI - Deep Learning Renal Segmentation for Fully Automated Radiation Dose Estimation in
Unsealed Source Therapy.
AB - Background: Convolutional neural networks (CNNs) have been shown to be powerful
tools to assist with object detection and-like a human observer-may be trained
based on a relatively small cohort of reference subjects. Rapid, accurate organ
recognition in medical imaging permits a variety of new quantitative diagnostic
techniques. In the case of therapy with targeted radionuclides, it may permit
comprehensive radiation dose analysis in a manner that would often be
prohibitively time-consuming using conventional methods. Methods: An automated
image segmentation tool was developed based on three-dimensional CNNs to detect
right and left kidney contours on non-contrast CT images. Model was trained based
on 89 manually contoured cases and tested on a cohort of patients receiving
therapy with 177Lu-prostate-specific membrane antigen-617 for metastatic prostate
cancer. Automatically generated contours were compared with those drawn by an
expert and assessed for similarity based on dice score, mean distance-to
agreement, and total segmented volume. Further, the contours were applied to
voxel dose maps computed from post-treatment quantitative SPECT imaging to
estimate renal radiation dose from therapy. Results: Neural network segmentation
was able to identify right and left kidneys in all patients with a high degree of
accuracy. The system was integrated into the hospital image database, returning
contours for a selected study in approximately 90 s. Mean dice score was 0.91 and
0.86 for right and left kidneys, respectively. Poor performance was observed in
three patients with cystic kidneys of which only few were included in the
training data. No significant difference in mean radiation absorbed dose was
observed between the manual and automated algorithms. Conclusion: Automated
contouring using CNNs shows promise in providing quantitative assessment of
functional SPECT and possibly PET images; in this case demonstrating comparable
accuracy for radiation dose interpretation in unsealed source therapy relative to
a human observer.
PMID- 29963497
TI - Liver Cancer Disparities in New York City: A Neighborhood View of Risk and Harm
Reduction Factors.
AB - Introduction: Liver cancer is the fastest increasing cancer in the United States
and is one of the leading causes of cancer-related death in New York City (NYC),
with wide disparities among neighborhoods. The purpose of this cross-sectional
study was to describe liver cancer incidence by neighborhood and examine its
association with risk factors. This information can inform preventive and
treatment interventions. Materials and methods: Publicly available data were
collected on adult NYC residents (n = 6,407,022). Age-adjusted data on liver and
intrahepatic bile duct cancer came from the New York State Cancer Registry (1)
(2007-2011 average annual incidence); and the NYC Vital Statistics Bureau (2015,
mortality). Data on liver cancer risk factors (2012-2015) were sourced from the
New York City Department of Health and Mental Hygiene: (1) Community Health
Survey, (2) A1C registry, and (3) NYC Health Department Hepatitis surveillance
data. They included prevalence of obesity, diabetes, diabetic control, alcohol
related hospitalizations or emergency department visits, hepatitis B and C rates,
hepatitis B vaccine coverage, and injecting drug use. Results: Liver cancer
incidence in NYC was strongly associated with neighborhood poverty after
adjusting for race/ethnicity (beta = 0.0217, p = 0.013); and with infection risk
scores (beta = 0.0389, 95% CI = 0.0088-0.069, p = 0.011), particularly in the
poorest neighborhoods (beta = 0.1207, 95% CI = 0.0147-0.2267, p = 0.026). Some
neighborhoods with high hepatitis rates do not have a proportionate number of
hepatitis prevention services. Conclusion: High liver cancer incidence is
strongly associated with infection risk factors in NYC. There are gaps in
hepatitis prevention services like syringe exchange and vaccination that should
be addressed. The role of alcohol and metabolic risk factors on liver cancer in
NYC warrants further study.
PMID- 29963498
TI - Recent Advances in the Treatment of Breast Cancer.
AB - Breast cancer (BC) is the most common malignancy in women. It is classified into
a few major molecular subtypes according to hormone and growth factor receptor
expression. Over the past few years, substantial advances have been made in the
discovery of new drugs for treating BC. Improved understanding of the biologic
heterogeneity of BC has allowed the development of more effective and
individualized approach to treatment. In this review, we provide an update about
the current treatment strategy and discuss the various emerging novel therapies
for the major molecular subtypes of BC. A brief account of the clinical
development of inhibitors of poly(ADP-ribose) polymerase, cyclin-dependent
kinases 4 and 6, phosphatidylinositol 3-kinase/protein kinase B/mammalian target
of rapamycin pathway, histone deacetylation, multi-targeting tyrosine kinases,
and immune checkpoints for personalized treatment of BC is included. However, no
targeted drug has been approved for the most aggressive subtype-triple negative
breast cancer (TNBC). Thus, we discuss the heterogeneity of TNBC and how
molecular subtyping of TNBC may help drug discovery for this deadly disease. The
emergence of drug resistance also poses threat to the successful development of
targeted therapy in various molecular subtypes of BC. New clinical trials should
incorporate advanced methods to identify changes induced by drug treatment, which
may be associated with the upregulation of compensatory signaling pathways in
drug resistant cancer cells.
PMID- 29963500
TI - Editorial: Tick-Host-Pathogen Interactions.
PMID- 29963499
TI - Further Characterization of the Capsule-Like Complex (CLC) Produced by
Francisella tularensis Subspecies tularensis: Protective Efficacy and Similarity
to Outer Membrane Vesicles.
AB - Francisella tularensis is the etiologic agent of tularemia, and subspecies
tularensis (type A) is the most virulent subspecies. The live vaccine strain
(LVS) of subspecies holarctica produces a capsule-like complex (CLC) that
consists of a large variety of glycoproteins. Expression of the CLC is greatly
enhanced when the bacteria are subcultured in and grown on chemically defined
medium. Deletion of two genes responsible for CLC glycosylation in LVS results in
an attenuated mutant that is protective against respiratory tularemia in a mouse
model. We sought to further characterize the CLC composition and to determine if
a type A CLC glycosylation mutant would be attenuated in mice. The CLCs isolated
from LVS extracted with 0.5% phenol or 1 M urea were similar, as determined by
gel electrophoresis and Western blotting, but the CLC extracted with urea was
more water-soluble. The CLC extracted with either 0.5% phenol or 1 M urea from
type A strains was also similar to the CLC of LVS in antigenic properties,
electrophoretic profile, and by transmission electron microscopy (TEM). The
solubility of the CLC could be further enhanced by fractionation with Triton X
114 followed by N-Lauroylsarcosine detergents; the largest (>250 kDa) molecular
size component appeared to be an aggregate of smaller components. Outer membrane
vesicles/tubules (OMV/T) isolated by differential centrifugation and micro
filtration appeared similar to the CLC by TEM, and many of the proteins present
in the OMV/T were also identified in soluble and insoluble fractions of the CLC.
Further investigation is warranted to assess the relationship between OMV/T and
the CLC. The CLC conjugated to keyhole limpet hemocyanin or flagellin was highly
protective against high-dose LVS intradermal challenge and partially protective
against intranasal challenge. A protective response was associated with a
significant rise in cytokines IL-12, IL-10, and IFN-gamma. However, a type A CLC
glycosylation mutant remained virulent in BALB/c mice, and immunization with the
CLC did not protect mice against high dose respiratory challenge with type A
strain SCHU S4.
PMID- 29963501
TI - Development of a High-Throughput ex-Vivo Burn Wound Model Using Porcine Skin, and
Its Application to Evaluate New Approaches to Control Wound Infection.
AB - Biofilm formation in wounds is considered a major barrier to successful
treatment, and has been associated with the transition of wounds to a chronic non
healing state. Here, we present a novel laboratory model of wound biofilm
formation using ex-vivo porcine skin and a custom burn wound array device. The
model supports high-throughput studies of biofilm formation and is compatible
with a range of established methods for monitoring bacterial growth, biofilm
formation, and gene expression. We demonstrate the use of this model by
evaluating the potential for bacteriophage to control biofilm formation by
Staphylococcus aureus, and for population density dependant expression of S.
aureus virulence factors (regulated by the Accessory Gene Regulator, agr) to
signal clinically relevant wound infection. Enumeration of colony forming units
and metabolic activity using the XTT assay, confirmed growth of bacteria in
wounds and showed a significant reduction in viable cells after phage treatment.
Confocal laser scanning microscopy confirmed the growth of biofilms in wounds,
and showed phage treatment could significantly reduce the formation of these
communities. Evaluation of agr activity by qRT-PCR showed an increase in activity
during growth in wound models for most strains. Activation of a prototype
infection-responsive dressing designed to provide a visual signal of wound
infection, was related to increased agr activity. In all assays, excellent
reproducibility was observed between replicates using this model.
PMID- 29963502
TI - Brucella abortus Traverses Brain Microvascular Endothelial Cells Using Infected
Monocytes as a Trojan Horse.
AB - Neurobrucellosis is an inflammatory disease caused by the invasion of Brucella
spp. to the central nervous system (CNS). The pathogenesis of the disease is not
well characterized; however, for Brucella to gain access to the brain parenchyma,
traversing of the blood-brain barrier (BBB) must take place. To understand the
CNS determinants of the pathogenesis of B. abortus, we have used the in vitro BBB
model of human brain microvascular endothelial cells (HBMEC) to study the
interactions between B. abortus and brain endothelial cells. In this study, we
showed that B. abortus is able to adhere and invade HBMEC which was dependent on
microtubules, microfilaments, endosome acidification and de novo protein
synthesis. After infection, B. abortus rapidly escapes the endosomal compartment
of HBMEC and forms a replicative Brucella-containing vacuole that involves
interactions with the endoplasmic reticulum. Despite the ability of B. abortus to
invade and replicate in HBMEC, the bacterium was unable by itself to traverse
HBMEC, but could traverse polarized HBMEC monolayers within infected monocytes.
Importantly, infected monocytes that traversed the HBMEC monolayer were a
bacterial source for de novo infection of glial cells. This is the first
demonstration of the mechanism whereby B. abortus is able to traverse the BBB and
infect cells of the CNS. These results may have important implications in our
understanding of the pathogenesis of neurobrucellosis.
PMID- 29963503
TI - Presentation and survival in patients with hematologic malignancies in Jos,
Nigeria: A retrospective cohort analysis.
AB - Background: Haematologic malignancies cause significant morbidity and mortality
and are not uncommon in resource-limited-low income countries. However, the
types, pattern of presentation and treatment outcomes vary across regions. We
assessed the presentation and overall survival over an 11-year period in adult
patients presenting with haematologic cancers in Jos, North Central Nigeria.
Materials and Methods: This retrospective outcome study evaluated patients who
presented with haematologic malignancies between 2005-2015 at the Jos University
Teaching Hospital (JUTH), Jos. Variables of interest were abstracted through
chart reviews. Descriptive statistics were used to evaluate baseline and follow
up parameters. Overall survival (OS) was assessed using Kaplan-Meier method.
Results: Sixty patients, contributing 25,994 person-days of follow-up were
evaluated. The mean age was 43+17 years and 61.7% were males. Thirty-one patients
(51.7%) presented with leukemia, 45.0% with lymphoma, and 3.3% with multiple
myeloma. Forty-two (70.0%) presented with advanced disease, 5 (5.2%) were HIV
positive and 4 (6.7%) had died at the end of follow-up. OS was 84.3% (95% CI:
58.1-94.7). Survival differed by disease group (p=0.01) and having fever at
presentation (p=0.02). Conclusion: We found long-term OS to be impacted by
disease type and status of fever at presentation. Disease-specific Strategies to
improve early diagnosis and therapies are needed to ensure optimal outcomes in
Nigerian patients.
PMID- 29963504
TI - Knowledge, demand, and the need of lay people for the orthodontic specialty in
comparison to other dental disciplines.
AB - OBJECTIVE: To assess the knowledge of, demand for, and need for the orthodontic
specialty in comparison to other dental fields in a sample of Saudi males.
MATERIALS AND METHODS: multiple choice questionnaire was designed to assess
participants' knowledge interest, demand, and need for treatment in the following
dental specialties: orthodontics, periodontics, prosthodontics, endodontics, and
restorative dentistry. Subjects desiring clinical examination underwent further
assessment to document their actual needs. In addition to the subjects' age, the
frequencies of tooth brushing, dental pain, treatment seeking, and routine
checkup were collected. Descriptive statistics and Pearson's Chi-square test were
applied to compare the percentages of the knowledge of, demand for, and need for
each dental discipline. The significance level was set at P < 0.05. RESULTS:
total of 1566 Saudi males completed the initial survey of dental knowledge, and
1406 subjects then completed the needs checklist. For the assessment of treatment
needed, a total of 177 Saudi males were examined. The average age was 31.25 years
(+/-13.44) and 30.61 years (+/-10.21) for the surveyed and examined groups,
respectively. Subjects' interest in orthodontic knowledge (25%) and demand
(27.6%) were not significantly different (P = 0.113), unlike the highly
significant difference in the need counterpart (62.5%, P < 0.001). Highly
significant differences (P < 0.001) were detected between the three outcome
frequencies (knowledge interest, demand, and need) within all dental disciplines,
except for the endodontic group where there was no significant difference
detected (P = 0.625). Further analysis for the differences between each possible
pairing of the three outcomes is highlighted. CONCLUSIONS: Subjects' knowledge of
orthodontics approximated their treatment demand. However, orthodontic need was
significantly much higher. Different patterns of distinction for other dental
specialties were detected and described.
PMID- 29963505
TI - Pharyngeal airway dimensional changes after premolar extraction in skeletal class
II and class III orthodontic patients.
AB - OBJECTIVE: To assess and compare the changes in pharyngeal airway space
dimensions following orthodontic treatment of skeletal class II and class III
facial deformities with premolar extraction. MATERIALS AND METHODS: Sixty pre and
posttreatment lateral cephalometric radiographs of patients who underwent fixed
orthodontic treatment with premolar extraction were collected. The sample was
divided into two groups - 32 patients with skeletal class II and 28 patients with
skeletal class III malocclusion. Both groups were subdivided into growing
patients (<16 years old) and adults (>16 years old). Nasopharyngeal,
palatopharyngeal, and glossopharyngeal airway space dimensions were measured in
the pretreatment (T0) and posttreatment (T1) cephalometric radiographs using
Dolphin Imaging 11.7 software. Two-way, repeated-measures analysis of variance
was used to assess the in-treatment changes. RESULTS: Nasopharyngeal airway
dimension showed similar significant increase in class II (P = 0.042) and class
III (P = 0.049) patients from T0 to T1, whereas palatopharyngeal and
glossopharyngeal dimensions were insignificantly decreased in both groups.
However, both malocclusions followed the same pattern of changes in relation to
airway dimensions. In addition, no significant statistical difference was found
in the airway spaces between growing and adult patients. CONCLUSIONS: Extraction
of premolars did not affect the pharyngeal dimensions except those of the
nasopharynx, which showed a significant increase after extraction in both groups.
PMID- 29963506
TI - Evaluation of root length following treatment with clear aligners and two
different fixed orthodontic appliances. A pilot study.
AB - OBJECTIVES: The purpose of this pilot study was to evaluate the root lengths of
upper incisors as an indication of the degree of orthodontically-induced apical
root resorption following treatment with Smart Track(r) aligners and compare it
with two different fixed orthodontic appliances - regular and Damon brackets -
using cone-beam computerized tomography (CBCT). MATERIALS AND METHODS: The sample
comprised 33 patients with class I malocclusion and 4-6 mm crowding divided in 3
groups; Group I: 11 patients treated with Smart Track(r) aligners, group II: 11
patients treated with Damon brackets, and group III: 11 patients with regular
brackets. Maxillary incisors teeth lengths were assessed using Dolphin imaging
software before and after treatment. All data were analyzed using analysis of
variance and t-test. RESULTS: All groups showed statistically significant root
resorption, 0-1.4 mm for clear aligners, 0.1-2.3 mm for Damon, and 0-2.5 mm for
regular brackets group. However, cases treated with fixed appliance in general
showed significantly higher resorption than those treated with Smart Track(r)
aligners (P < 0.05). CONCLUSION: Orthodontically-induced root resorption, as
evaluated by root length, is an inevitable drawback with different orthodontic
techniques. However, the use of Smart Track(r) aligners showed less root
resorption relative to regular fixed appliances.
PMID- 29963507
TI - Shear bond strength of new and rebonded orthodontic brackets to the enamel
surfaces.
AB - OBJECTIVES: The objective of this study was to compare the shear bond strength
(SBS) of new and rebounded orthodontic brackets bonded to the buccal sound and
cleaned enamel surfaces using two orthodontic adhesives: resin-modified glass
ionomer (RMGI) and resin-composite. MATERIALS AND METHODS: Forty premolars were
randomly allocated into four groups, 10 teeth/group. New and rebonded brackets
were bonded to sound and cleaned enamel surface, and then were subjected to
thermocycling. The bond strength was determined using a universal testing machine
at a crosshead speed of 1 mm/min. Remaining adhesives on enamel after bracket
debonding was scored independently by two investigators who were not aware of the
four different groups, using adhesive remnant index (ARI). RESULTS: There was a
statistical significant difference in SBS of the four groups (P = 0.005). SBS
values were significantly higher with cleaned enamel surfaces after adhesive
removal compared to sound enamel. SBS was significantly higher for rebonded
brackets, when compared with the new brackets. No significant difference was
found between the two adhesives types. The level of agreement between the two
raters was higher toward the classification of higher categories of ARI (scores 5
and 6) with agreement percentage 91.7% and 100%, respectively. There was more
adhesive remained among resin-composite groups. CONCLUSIONS: The bond strength of
debonded sandblasted stainless-steel brackets was higher than new brackets. Resin
composite and RMGI orthodontic adhesives used in this study exhibited sufficient
SBS values for bonding brackets to sound and cleaned enamel and comparable to
each other.
PMID- 29963508
TI - Effects of force magnitude on torque control in the correction of bimaxillary
protrusion with mass retraction.
AB - OBJECTIVES: This study was designed to explore whether force magnitude would
influence incisor torque control and the overall outcome in patients with
bimaxillary protrusion who need mass incisor retraction. MATERIALS AND METHODS:
Forty-one female patients (aged > 15 years) with bimaxillary protrusion requiring
mass incisor retraction were selected. Two sliding mechanics were utilized, with
the elastic group receiving a light force of ~100 g by wearing elastics and the
power chain group receiving a moderate force of ~250 g by power chain. Lateral
cephalograms obtained before and after treatment were traced and measured.
RESULTS: Patients in both groups displayed maxillary protrusion with a similar
skeletal class II tendency. A longer treatment time was found in the elastic
group. No difference in the distance of incisor tip movement was observed between
the two groups; however, a larger inclination of upper incisors was found in the
elastic group, indicating less loss of torque. In addition, larger reduction in
Sella-Nasion-A and A-Nasion-B angle was observed in the elastic group, which was
accompanied by a larger ratio of upper lip retraction to upper incisor retraction
as well as more upper lip retraction. CONCLUSIONS: Sliding mechanics with
elastics to generate light forces can achieve better torque control with more
reduction in skeletal and soft tissue protrusion.
PMID- 29963509
TI - Assessment of the validity of orthopantomographs in the evaluation of mandibular
steepness in Libya.
AB - AIM: The value of gonial angle indicates the range of steepness as well as the
direction of mandibular growth. Exact measurement of right (R) and left (L)
gonial angles from a lateral cephalometric radiograph is challenging due to the
superimposition of both sides. Thus, the aim of the present study was to assess
the potential of determining accurate measurement of R and L gonial angles by
employing orthopantomographs (OPGs) and to compare the findings with the
measurements obtained from lateral cephalometric radiographs. MATERIALS AND
METHODS: total of 125 standardized panoramic as well as lateral cephalometric
radiographs of Libyan subjects were obtained from the orthodontic clinical
records (36 males and 89 females). Mandibular inclination was computed by
averaging the R and L gonial angles produced by drawing tangents to the inferior
border of the mandible and to the distal aspect of the ascending ramus and the
condylon on each OPG. Moreover, similar steps were followed to extract the gonial
angle from the cephalometric radiographs. RESULTS: Student's paired t-tests
revealed no significant discrepancies between the R and L gonial angle values
extracted from the OPG (123.88 degrees +/- 6.53 degrees and 123.27 degrees +/-
6.55 degrees ) at P = 0.0.070. The mean values of the gonial angle (average of
the R and L mean values) extracted from the OPG (123.58 degrees +/- 6.38 degrees
) and cephalometric radiographs (125.14 degrees +/- 6.23 degrees ) were not
significantly different (P = 0.084). Furthermore, Pearson's correlation
coefficient revealed strong correlation between the value of the gonial angle
measured in the cephalometric radiograph and the mean value extracted from the
OPG (r = 0.897 at P < 0.001). CONCLUSION: OPGs are as useful as lateral
cephalometric radiographs in the assessment of mandibular inclination and
steepness in Libyan subjects. They have the added advantage of reducing patient
exposure to radiation by cutting the number of radiographs required during
diagnosis.
PMID- 29963510
TI - How much progress has Blood Research made since the change of the journal title
in 2013.
AB - Background: Blood Research (formerly) was renamed 5 years ago. It aimed to
identify the progress of the renamed journal at the international level based on
journal metrics. Methods: Journal metrics, including total cites, impact factor,
and Hirsch index were calculated or found from Scopus, SCimago Journal & Country
Rank, and Web of Science on March 27, 2018. Results: The number of citable
articles from 2013 to 2017 was 196, and that of non-citable articles was 157. The
authors belonged to 25 countries. The editorial board members were from 33
countries. Total cites in Scimago Journal & Country Rank and Web of Science Core
Collection in 2017 was 257 and 235, respectively. The cites per two years from
Scimago Journal & Country Rank and the calculated impact factor from Web of
Science Core Collection in 2016 were 1.353 and 1.382, respectively. The number of
citing authors' countries in Web of Science Core Collection was 61. The number of
citing journals in Web of Science Core Collection was 422. In 2016, the Hirsch
index was 12 for Scimago Journal & Country Rank, and that in Web of Science Core
Collection was 10. Conclusion: Since the title change, Blood Research has
progressed rapidly on the international scene in terms of journal metrics. In
particular, the results of total cites, impact factor, and Hirsch index were
outstanding. This will enable its promotion as a high branded journal in the
hematology category.
PMID- 29963511
TI - The ubiquitous parasite: leishmaniasis in an elderly man.
PMID- 29963512
TI - Megakaryoblasts in a newborn with Down syndrome.
PMID- 29963513
TI - Splenic marginal zone lymphoma relapsing as miliary lung mottling: an unusual
presentation.
PMID- 29963514
TI - Del(5q) myelodysplastic syndrome combined with pure red cell aplasia.
PMID- 29963515
TI - Busulfan plus melphalan versus high-dose melphalan as conditioning regimens in
autologous stem cell transplantation for newly diagnosed multiple myeloma.
AB - Background: High-dose melphalan (HDMEL) represents the standard conditioning
regimen before autologous stem cell transplant (ASCT) in multiple myeloma (MM),
but recent updates have suggested combination of melphalan with bulsulfan (BUMEL)
is also associated with favorable outcomes. We performed the current study to
address the lack of comparative studies between the two conditioning regimens in
Asian populations. Methods: Using the Korean National Health Insurance and Korean
Health Insurance Review and Assessment Service databases, 1,304 patients newly
diagnosed with MM undergoing ASCT between January 2010 and December 2014 were
identified. Patients were divided according to conditioning regimen (HDMEL vs.
BUMEL), and after case matching, 428 patients undergoing HDMEL conditioning were
compared to 107 patients undergoing BUMEL conditioning with respect to clinical
course and treatment outcomes. Results: The 3-year progression-free survival
(PFS) was 52.5% for the HDMEL conditioning group versus 70.3% for the BUMEL
conditioning group (P=0.043). The 3-year overall survival (OS) was 82.0% versus
83.5% (P=0.525), respectively. Although not statistically significant, BUMEL
conditioning was associated with more platelet transfusion, while HDMEL was
associated with more granulocyte colony stimulating factor support. In
multivariate analysis, BUMEL conditioning was not inferior to HDMEL conditioning
in regard to both PFS and OS. Conclusion: Our study confirmed that BUMEL is an
effective and well-tolerated alternative to HDMEL conditioning, with better PFS.
PMID- 29963517
TI - Impact of rituximab and half-dose CHOP as primary therapy for untreated
symptomatic Waldenstrom Macroglobulinemia: review of a combined regimen of
rituximab with an alkylating agent.
AB - Background: Waldenstrom Macroglobulinemia (WM) is a rare subtype of indolent B
cell lymphoma, and prospective randomized studies on WM are scarce. The R-CHOP
therapy [rituximab (R), cyclophosphamide, hydroxy-doxorubicin, vincristine, and
prednisone] is a popular and recommended regimen for primary therapy, prescribed
by several treatment guidelines for WM. However, treatment with R-CHOP is
accompanied by severe myelosuppression and high rates of peripheral neuropathy.
Therefore, we retrospectively evaluated the efficacy and toxicity of half-dose
CHOP combined with R as a primary therapy for WM. Methods: Patients with
untreated symptomatic WM, treated at the Disaster Medical Center between April
2011 and September 2016, were retrospectively analyzed after administration of 6
cycles of half-dose R-CHOP for every 3 weeks. The response, median time to
response, best response, progression-free survival, overall survival, and
toxicities were evaluated. Results: Of the 20 WM patients analyzed, 16 (80%)
received half-dose R-CHOP without vincristine, and 13 (65%) responded to the
treatment. With a median follow-up duration of 26.3 months, the 2-year
progression-free survival and 2-year overall survival rates were 70 and 93.3%,
respectively. The median time to response and best response were 6 and 9.9 weeks,
respectively. Grade 3/4 leukocytopenia, neutropenia, febrile neutropenia, and
Grade 1 peripheral neuropathy developed in 32, 37, 0, and 21% of patients,
respectively. Conclusion: The half-dose R-CHOP is an effective and well-tolerated
primary therapy for WM. To the best of our knowledge, this is the first study
reporting the use of a reduced-dose R-CHOP regimen for the primary treatment of
WM.
PMID- 29963516
TI - Clinical characteristics and treatment courses for cytomegalovirus-associated
thrombocytopenia in immunocompetent children after neonatal period.
AB - Background: Cytomegalovirus (CMV) causes severe diseases in premature infants and
immunocompromised hosts, and antiviral therapy is often required for disease
control. However, the clinical manifestations and treatment courses for CMV
associated thrombocytopenia in immunocompetent children are unclear. Methods:
Medical records of the children who suffered from thrombocytopenia, and showed
positive CMV polymerase chain reaction and CMV-like symptoms were retrospectively
analyzed at three university hospitals in Daegu from January 2000 to March 2017.
Patients suffering from leukemia, immunodeficiency, and other infections were
excluded. Results: Among 1,065 children with thrombocytopenia, 29 (2.7%)
displayed CMV-associated thrombocytopenia. The median age at diagnosis was 15
months and the median platelet count was 26,000/uL. They were classified into the
CMV-induced thrombocytopenia (23/29) and CMV-related secondary immune
thrombocytopenia (ITP, 6/29) groups. Fourteen subjects had hepatic dysfunction,
four had Evans syndrome, two had pneumonitis, and one had gastritis. IVIG was
used for 21 patients, and six patients among them showed recurrence, for whom
IVIG or antiviral therapy was used. All, except one, recurrent or chronic cases
belonged to the CMV-induced thrombocytopenia group. Antiviral therapy was used
more frequently for the CMV-induced thrombocytopenia group (8/23, 34.8%) than for
the CMV-related secondary ITP group (0/6); however, the results were not
statistically significant (P=0.148). Conclusion: CMV is a rare but unique
etiology of thrombocytopenia, and observed even in healthy children after the
neonatal period. About one-third patients need antiviral therapy for disease
control. Further, CMV-induced thrombocytopenia is more complex than CMV-related
secondary ITP.
PMID- 29963518
TI - Effectiveness of darbepoetin alfa in multiple myeloma patients receiving
chemotherapy including novel agents.
AB - Background: The aim of this study was to evaluate the effects of darbepoetin alfa
(DA) on hemoglobin (Hb) concentration and the need for transfusions in multiple
myeloma (MM) patients receiving chemotherapy with novel agents. Methods: Of 251
patients with MM who received DA therapy for at least 4 weeks, 142 who did not
receive RBC transfusion during 4 weeks after DA initiation and started DA therapy
at baseline Hb <10.0 g/dL were analyzed. Results: After 4 weeks of DA therapy, 80
(60.6%) of 132 patients with evaluable data had Hb that increased >=1.0 g/dL from
baseline, while 50 (37.9%) had Hb that increased >=2.0 g/dL from baseline.
Pretreatment Hb level did not correlate with the proportion of patients with
increased Hb. The median duration of DA therapy was 9.0 weeks. At the end of DA
therapy, of 135 patients with evaluable data, 86 (60.6%) had Hb that increased
>=1.0 g/dL from baseline, while 67 (47.2%) had Hb that increased >=2.0 g/dL from
baseline. Stage III disease according to the International Staging System and
absence of myeloma bone disease at diagnosis were independent predictors of
higher Hb response during early DA therapy. Conclusion: We demonstrated the
efficacy of DA therapy in a homogeneous group of MM patients receiving
chemotherapy. DA therapy significantly increased Hb concentration, regardless of
baseline Hb level.
PMID- 29963519
TI - Clinical characteristics and outcomes of thrombotic microangiopathy in Malaysia.
AB - Background: Thrombotic microangiopathy (TMA) with non-deficient ADAMTS-13 (a
disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) outcome
is unknown hence the survival analysis correlating with ADAMTS-13 activity is
conducted in Malaysia. Methods: This was a retrospective epidemiological study
involving all cases of TMA from 2012-2016. Results: We evaluated 243 patients
with a median age of 34.2 years; 57.6% were female. Majority of the patients were
Malay (62.5%), followed by Chinese (23.5%) and Indian (8.6%). The proportion of
patients with thrombotic thrombocytopenic purpura (TTP) was 20.9%, 72.2% of which
were acquired while 27.8% were congenital. Patients with ADAMTS-13 activity >=5%
had a four-fold higher odds of mortality compared to those with ADAMTS-13
activity <5% (odds ratio: 4.133, P=0.0425). The mortality rate was 22.6% (N=55).
Most cases had secondary etiologies (42.5%), followed by acquired TTP (16.6%),
atypical hemolytic uremic syndrome (HUS) or HUS (12.8%) and congenital TTP
(6.4%). Patients with secondary TMA had inferior overall survival (P=0.0387). The
secondary causes comprised systemic lupus erythematosus (30%), infection (29%),
pregnancy (10%), transplant (8%), malignancy (6%), and drugs (3%). Transplant
associated TMA had the worst OS (P=0.0016) among the secondary causes. Plasma
exchange, methylprednisolone and intravenous immunoglobulin were recorded as
first-line treatments in 162 patients, while rituximab, bortezomib, vincristine,
azathioprine, cyclophosphamide, cyclosporine, and tacrolimus were described in 78
patients as second-line treatment. Conclusion: This study showed that TMA without
ADAMTS-13 deficiency yielded inferior outcomes compared to TMA with severeADAMTS
13 deficiency, although this difference was not statistically significant.
PMID- 29963520
TI - Leukemia propagating cells in Philadelphia chromosome-positive ALL: a resistant
phenotype with an adverse prognosis.
AB - Background: Targeted therapy has revolutionized the management of Philadelphia
chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); however, relapse
still occurs because of the presence of quiescent stem cells, termed leukemia
propagating cells (LPCs). This study aimed to assess the phenotypic diversity of
LPCs in adult patients with Ph+ B-Acute ALL (B-ALL) and to assess its prognostic
impact. Methods: Seventy adults with newly diagnosed Ph+ B-ALL were recruited at
the Mansoura Oncology Center. Multiparameter flow cytometry studies of
mononuclear blast cells for cluster of differentiation (CD)34, CD38, and CD58
were performed. Results: Seventeen patients had blasts with the pattern of LPCs
(CD34+CD38-CD58-), while 53 cases had other diverse phenotypic patterns. The rate
of complete response was significantly lower in patients with the LPC phenotype
(47% vs. 81%, P=0.006). The median time to achieve a complete response was
prolonged in patients with the CD34+CD38-CD58- phenotype (48 vs. 32 days,
P=0.016). The three-year overall survival was significantly lower in patients
with the CD34+CD38-CD58- phenotype (37% vs. 55% respectively, P=0.028).
Multivariate analysis showed that the CD34+CD38- CD58- phenotype was an
independent risk factor for overall survival. Conclusion: The presence of
CD34+CD38-CD58- LPCs at diagnosis allows rapid identification of higher risk
patients. Risk stratification of these patients is needed to further guide
therapy and develop effective LPCs-targeted therapy to improve treatment outcome.
PMID- 29963521
TI - Allogeneic hematopoietic stem cell transplantation in congenital
hemoglobinopathies with myeloablative conditioning and rabbit anti-thymocyte
globulin.
AB - Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a
curative therapy for beta-thalassemia major (TM) and sickle cell disease (SCD) in
children. Graft-versus-host disease (GVHD) and treatment-related mortality (TRM)
remain significant challenges to improving survival after HSCT. Here, we analyzed
the outcome of TM and SCD patients, who received allogeneic HSCT with
myeloablative conditioning at our institution. Methods: Twenty-two patients (15
TM, 7 SCD), with a median age of 9 years (range, 1.6-16.9), underwent allogeneic
HSCT using busulfan, cyclophosphamide and rabbit anti-thymocyte globulin-based
conditioning. Cells were derived from either the bone marrow (8 patients), or
peripheral blood stem cells (14 patients). The majority of patients received HSCT
from a matched sibling donor (N=18). GVHD prophylaxis included cyclosporine and
short course methotrexate. Results: All patients achieved donor engraftment. Two
SCD patients died from TRM-related grade IV gut GVHD (N=1) or severe
bronchiolitis obliterans (BO) (N=1). Cumulative incidence of acute and chronic
GVHD was 36.4% and 32.7%, respectively. Veno-occlusive disease (VOD) occurred in
8 patients (36.4%), but resolved in all instances. Epstein-Barr virus (EBV)
related post-transplantation lymphoproliferative disease (PTLD) occurred in 1
patient. The overall survival (OS) was 90.9% (TM 100%, SCD 71.4%), with all
patients achieving transfusion independence, while 8 achieved complete donor
chimerism. Conclusion: Busulfan, cyclophosphamide, and ATG-based conditioning for
HSCT of TM and SCD patients did not result in graft failure, although
modifications may be required to reduce VOD incidence. Further changes to donor
type and cell source prioritization are necessary to minimize TRM and morbidity
caused by GVHD.
PMID- 29963522
TI - The incidence of atypical patterns of BCR-ABL1 rearrangement and molecular
cytogenetic response to tyrosine kinase inhibitor therapy in newly diagnosed
cases with chronic myeloid leukemia (CML).
AB - Background: To analyze the frequency of atypical fluorescence in situ
hybridization signal patterns and estimate the complete cytogenetic response
(CCyR) and major molecular response (MMR) during 12 months of tyrosine kinase
inhibitor therapy in patients with newly diagnosed chronic myeloid leukemia.
Methods: The study included bone marrow and peripheral blood samples from 122
patients with newly diagnosed chronic myeloid leukemia. Detection of the
breakpoint cluster region-Abelson fusion gene (BCR-ABL1) was performed using
fluorescence in situ hybridization with a dual-color dual-fusion translocation
probe, and MMR analysis was performed using the real-time quantitative polymerase
chain reaction method. Results: Variant translocation was determined in 10
samples and a deletion on the derivative chromosome 9 (del/der(9)) was found in
20 samples. The rates of CCyR and MMR were similar between patients with
reciprocal translocation, variant translocation, deletion of derivative BCR, or
ABL1-BCR fusion gene. The Kaplan-Meier test did not show any significant
differences in the rates of CCyR and MMR among those groups of patients.
Conclusion: The frequencies of variant translocation and del/der(9) in the
present study agree with the results of other studies performed worldwide. No
differences were observed in the rates of CCyR and MMR between patients with
atypical patterns and reciprocal translocation.
PMID- 29963523
TI - Synchronous hairy cell leukemia and chronic lymphocytic leukemia: a case report
with a brief review of literature.
PMID- 29963525
TI - Evaluation of thrombocytopenia in the hematology clinic: a case series from a
large tertiary care center.
PMID- 29963524
TI - The first concurrent diagnosis of acute symptomatic Babesiosis and chronic
myeloid leukemia in a healthy young adult.
PMID- 29963526
TI - Microangiopathic hemolytic anemia as initial presentation of recurrent colon
cancer.
PMID- 29963528
TI - Peripheral neuropathy associated with imatinib therapy for chronic myeloid
leukemia.
PMID- 29963527
TI - Long-term control of refractory follicular lymphoma after treatment of secondary
acute promyelocytic leukemia with arsenic trioxide (As2O3) and all-trans retinoic
acid (ATRA).
PMID- 29963529
TI - Primary CNS lymphoma: latest updates and a 10-year monocenter experience.
PMID- 29963530
TI - Acetate moderately attenuates the generation of neutrophil extracellular traps.
PMID- 29963531
TI - Granulocytic dysplasia: an indicator of clonal evolution in patients with chronic
myeloid leukemia.
PMID- 29963532
TI - Retraction.
AB - [This retracts the article on p. 87 in vol. 53, PMID: 29662870.].
PMID- 29963533
TI - Surgical hand antisepsis: experimental study.
AB - Purpose: Nosocomial infections account for one of the most serious complications
in hospitalized patients around the world. Surgical site infections have
significant economic implications, and surgical antisepsis plays an important
role in such processes. Methods: With prior approval by the Institutional Review
Board and informed consent, 10 volunteers were randomly assigned to 3 protocols
on hand antisepsis: protocol A (chloroxylenol 3%), protocol B (benzalkonium
chloride at 1%), and protocol C (ethyl alcohol 61%, 1% chlorhexidine gluconate).
Smears from both hands were cultured after each hand pro tocol (t0) and at the
end of suturing (t1). Colony forming units were counted (CFUs on blood agar
dishes) with digital counting software (Open CFU). Friedman test was used to
compare the mean values among the groups, and a Bonferroni correction was made to
determine the dissimilar group, with a P = 0.015. Results: At t0 for protocol A
the CFU count was 82.8 +/- 1.3; protocol B was 9.7 +/- 30; protocol C was 0.1 +/-
0.3 (P < 0.001). At t1 for protocol A the CFU was 80.7 +/- 89.4; protocol B was
7.5 +/- 32; protocol C was 0.0 +/- 0.0 (P < 0.001). No adverse events were
present among the subjects. Conclusion: Ethyl alcohol at 61% with 1%
chlorhexidine gluconate showed higher efficacy than the traditional washing
antiseptics.
PMID- 29963534
TI - Meta-analysis of randomized controlled trials on the efficacy of daikenchuto on
improving intestinal dysfunction after abdominal surgery.
AB - Purpose: Intestinal dysfunction is one of the most common complications in
patients after abdominal surgery. Daikenchuto (DKT), a traditional herbal
medicine, is recently employed to improve postoperative intestinal dysfunction.
The aim of this meta-analysis was to assess the efficacy of DKT in improving
intestinal dysfunction after abdominal surgery. Methods: PubMed, Embase, and the
Cochrane library were systematically searched to identify randomized controlled
trails (RCTs) in adult patients undergoing abdominal surgery, who were randomly
distributed to administrate DKT and placebo. The primary outcomes included the
time to first postoperative flatus or bowel movement. We used random-effects
models to calculate summary mean differences (MDs) with 95% confidence intervals
(CIs). Results: Nine RCTs totaling 1,212 patients (618 in DKT, 594 in control
group) were included in our study. Compared with control group, DKT can
effectively improve postoperative intestinal dysfunction by shortening the time
to first postoperative flatus (MD, -0.41; 95% confidence interval [CI], -0.66 to
0.16; P = 0.001) with significant heterogeneity (I2 = 71%, P = 0.004), and bowel
movement (MD, -0.65; 95% CI, -0.97 to -0.32; P < 0.001) without significant
heterogeneity (I2 = 40%, P = 0.14). Sensitivity analyses by indication of surgery
and type of surgery yielded similar results. Conclusion: These data provide
limited evidence that DKT shows efficacy on improving intestinal dysfunction
after abdominal surgery. However, the results should be interpreted cautiously,
due to the heterogeneity of the studies included. Thus, the efficacy of DKT on
improving postoperative intestinal dysfunction warrants further investigation.
PMID- 29963535
TI - Safety of medial dissection of the thyroid gland along the trachea based on
anatomic constancy of the laryngeal entry point of the recurrent laryngeal nerve.
AB - Purpose: The purpose of this study was to determine the extent of safety of
medial dissection of the thyroid gland along the trachea. Medial to lateral
dissection of the thyroid gland along the trachea after early division of the
isthmus has been known to be a useful technique in thyroid surgery, especially
for difficult cases, but the risk of injury of the recurrent laryngeal nerve
(RLN) has constrained thyroid surgeons from utilizing this technique to its full
extent. Methods: Distances of the laryngeal entry point (LEP) of 134 RLNs of 71
patients from the midline of the trachea, and some other anatomical distances,
were measured intraoperatively. The relationships of the intraoperatively
measured data with circumferences of the cartilaginous portion of the trachea
(CCT) around LEP measured preoperatively by CT scan were evaluated. Results: LEP
was always located within 2 mm vertically from the horizontally extended line of
the inferior border of the cricoid cartilage and was the closest point from the
midline in the whole course of the RLN. The distance between LEP and the midline
was very closely correlated with CCT measured on preoperative CT scan, and it can
be accurately calculated with a regression equation; Distance between LEP and the
midline = (0.42 * CCT) + (1.2 * sex) + 3.2 (mm) (sex: female=0, male=1; R2 =
0.85). Conclusion: Early division of the isthmus and dissecting the thyroid off
the trachea to the calculated extent is a safe and effective procedure.
PMID- 29963536
TI - Transduodenal ampullectomy for ampullary tumors - single center experience of
consecutive 26 patients.
AB - Purpose: Transduodenal ampullectomy (TDA) has been reported in a limited number
of cases and in a small number of case series. The aim of this study was to
analyze perioperative and long-term oncological outcomes of patients with
ampullary tumors who underwent TDA in a single large-volume center. Methods:
Through a retrospective review of data from 2004 to 2016, we identified 26
patients who underwent TDA at Asan Medical Center. Results: Eleven of 26 patients
underwent TDA for T1 and carcinoma in situ (high-grade dysplasia) cancer; these
patients are still alive without recurrence. A major in-hospital complication
(3.8%) occurred in 1 case, but there was no case of 90-day mortality. In
addition, none of the patients was diagnosed as having newly developed diabetes
mellitus after TDA. No significant differences were found between open and
laparoscopic-TDA in terms of operation time, painkiller use, and hospital stay.
Conclusion: TDA is a feasible and effective surgical procedure for the treatment
of selected patients with ampullary tumors. It is an alternative treatment option
in cases of ampullary tumors not amenable to endoscopic papillectomy or
pancreaticoduodenectomy.
PMID- 29963537
TI - Pancreatic fistula and mortality after surgical management of pancreatic trauma:
analysis of 81 consecutive patients during 11 years at a Korean trauma center.
AB - Purpose: Pancreatic trauma is infrequent because of its central, deep anatomical
position. This contributes to a lack of surgeon experience and many debates exist
about its standard care. This study aimed to investigate the postoperative
pancreatic fistula (POPF) and mortality of pancreatic trauma after operation.
Methods: We reviewed records in the trauma registry of our institution submitted
from January 2006 to December 2016. The grade of pancreatic injury, surgical
management, morbidity, mortality, and other clinical variables included in the
analyses. Results: Data from a total of 26,072 trauma patients admitted to the
Emergency Department were analyzed. Pancreatic trauma was observed in 114 of
these patients (0.44%). Laparotomy was performed in 81 patients (2 pan creatico
duodenectomies, 2 pancreaticogastrostomies, peripancreatic drainage in 41
patients, distal pancreatectomies in 34 patients, and 9 patients who underwent
surgery for damage control). The incidence of POPF was 38.3%. The overall
mortality was 8.8% (7 of 81). In multivariate analysis, pancreas injury grade IV
(>=4) (adjusted odds ratio [AOR], 4.071; P = 0.029) and preoperative peritonitis
signs (AOR, 2.903; P = 0.039) were independent risk factors for POPF. All
patients who died had also another major abdominal injury (>=grade 3). Multiorgan
failure was a major cause of death (6 of 7, 85.7%). The mortality rate of
isolated pancreas injury was 0%. Conclusion: The pancreas injury grade and
preoperative peritonitis were significant risk factors of POPF. The mortality
rate of isolated pancreatic trauma was very low.
PMID- 29963538
TI - Comparative analysis of robot-assisted vs. open abdominoperineal resection in
terms of operative and initial oncological outcomes.
AB - Purpose: The present study aimed to objectively evaluate robot-assisted
abdominoperineal resection (APR) in comparison with open APR, in terms of
operative elements and initial oncological outcomes. Methods: A total of 118
patients with lower rectal adenocarcinoma who had undergone curative APR were
consecutively enrolled between June 2010 and June 2016, i.e., robot-assisted
group (n = 40) and open group (n = 78). Results: Transabdominal extralevator
muscle excision was more frequently performed in the robot-assisted group than in
the open group (68% vs. 42%, P = 0.012). In the robot-assisted group, the pain
score at one day after surgery was less than in the open group, and the
resumption of bowel function was earlier (P = 0.043 and P = 0.002, respectively).
The occurrence of circumferential resection margin involvement (CRM+) was more
than 5 times greater in the open group than in the robot-assisted group,
presenting a marginal significance (P = 0.057). Although important postoperative
morbidity did not generally differ between the 2 groups, voiding difficulty and
male sexual dysfunction appeared to be encountered more frequently in the open
group than in the robot-assisted group. Conclusion: The robot-assisted APR
facilitated transabdominal extralevator excision and bowel recovery and
demonstrated a trend towards reduced CRM+.
PMID- 29963539
TI - Intraoperative management of liver transplant recipients having severe renal
dysfunction: results of 42 cases.
AB - Purpose: Whereas continuous renal replacement therapy (CRRT) has been utilized
during liver transplantation (LT), there was a lack of evidence to support this
practice. We investigated the adverse events at the perioperative periods in
recipients of LT who received preoperative CRRT without intraoperative CRRT.
Methods: We retrospectively reviewed medical records of adult patients (age >= 18
years) who received LT between December 2009 and May 2015. Perioperative data
were collected from the recipients, who received preoperative CRRT until
immediately before LT, because of refractory renal dysfunction. Results: Of 706
recipients, 42 recipients received preoperative CRRT. The mean (standard
deviation) Model for end-stage liver disease score were 49.6 (13.4). Twenty-six
point two percent (26.2%) of recipients experienced the serum potassium > 4.5
mEq/L before reperfusion and treated with regular insulin. Thirty-eight point one
percent (38.1%) of recipients were managed with sodium bicarbonate because of
acidosis (base excess < -10 mEq/L throughout LT). All patients finished their
operations without medically uncontrolled complications such as severe
hyperkalemia (serum potassium > 5.5 mEq/L), refractory acidosis, or critical
arrhythmias. Mortality was 19% at 30 day and 33.3% at 1 year. Conclusion:
Although intraoperative CRRT was not used in recipients with severe preoperative
renal dysfunction, LT was safely performed. Our experience raises a question
about the need for intraoperative CRRT.
PMID- 29963540
TI - Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs.
AB - Introduction: Ventilation causes cerebral white matter inflammation and injury,
which is exacerbated by intrauterine inflammation. However, the effects on
cortical gray matter are not well-known. Our aim was to examine the effect of
ventilation on the cerebral cortex of near-term lambs exposed to intrauterine
inflammation. Method:Pregnant ewes at 119 +/- 1 days gestation received an intra
amniotic injection of saline or lipopolysaccharide (LPS; 10 mg). Seven days
later, lambs were randomized to either a high tidal volume injurious ventilation
strategy (INJSALN = 6, INJLPSN = 5) or a protective ventilation strategy
(PROTSALN = 5, PROTLPSN = 6). Respiratory parameters, heart rate and blood gases
were monitored during the neonatal period. At post-mortem, the brain was
collected and processed for immunohistochemical assessment. Neuronal density
(NeuN), apoptotic cell death (caspase 8 and TUNEL), microglial density (Iba-1),
astrocytic density (GFAP), and vascular protein extravasation (sheep serum) were
assessed within the frontal, parietal, temporal and occipital lobes of the
cerebral cortex. Results:A significant reduction in the number of neurons in all
cortical layers except 4 was observed in LPS-exposed lambs compared to controls
(layer #1: p = 0.041; layers #2 + 3: p = 0.023; layers #5 + 6: p = 0.016). LPS
treatment caused a significant increase in gray matter area, indicative of edema.
LPS+ventilation did not cause apoptotic cell death in the gray matter.
Astrogliosis was not observed following PROT or INJ ventilation, with or without
LPS exposure. LPS exposure was associated with vascular protein extravasation.
Conclusion:Ventilation had little effect on gray matter inflammation and injury.
Intrauterine inflammation reduced neuronal cell density, caused edema of the
cortical gray matter, and blood vessel extravasation in the brain of near-term
lambs.
PMID- 29963541
TI - Congenital Heart Defects and Ciliopathies Associated With Renal Phenotypes.
AB - Congenital heart disease (CHD) is one of the most common birth defects, and
recent studies indicate cilia-related mutations play a central role in the
genetic etiology of CHD. As cilia are also known to have important roles in
kidney development and disease, it is not surprising that renal anomalies were
found to be enriched among CHD mutant mice recovered in a large-scale mouse
forward genetic screen. Indeed 42% of mutations identified to cause both CHD and
renal anomalies were cilia-related. Many of these cilia mutations comprise cilia
transition zone or inversin compartment components, consistent with the known
role of these cilia proteins in a wide variety of ciliopathies. The high
prevalence of CHD with congenital anomalies of the kidney and urinary tract
(CAKUT) observed in mice was also corroborated with clinical studies that showed
20-30% of CHD patients have renal anomalies. Together these findings suggest CHD
patients may benefit from early screening for renal anomalies to allow early
diagnosis and intervention to improve outcome for this vulnerable patient
population.
PMID- 29963542
TI - Using Intervention Mapping to Develop and Adapt Two Educational Interventions for
Parents to Increase HPV Vaccination Among Hispanic Adolescents.
AB - Introduction: Effective interventions to increase HPV vaccination are needed to
reach national vaccination goals and to reduce later HPV-related cancer
disparities. We used Intervention Mapping (IM) to develop and adapt a theory- and
evidence-based educational intervention targeting parents of Hispanic adolescents
to increase HPV vaccination. Methods: We followed IM steps 1-6 to: (1) develop a
logic model and identify modifiable factors associated with vaccination among
Hispanic adolescents by conducting literature reviews, focus groups, and in-depth
interviews with Hispanic parents; (2) develop outcomes, write performance
objectives, and develop a matrix of change objectives; (3) develop and identify a
program theme, program components, theoretical methods, and practical
applications; (4) develop an intervention design plan; (5) develop implementation
strategies; and (6) develop an evaluation plan. We completed Steps 1-6 for to
develop an intervention targeting parents of females, and we followed the steps
again to adapt the program once HPV vaccine recommendations included males.
Results: The program Por Nuestras Hijas (For Our Daughters) included two
components: a print fotonovela and a tailored interactive multimedia intervention
(TIMI). The program utilized the methods tailoring, targeting, framing,
anticipated regret, modeling, skill building, and education and counseling to
target the following determinants: parental knowledge, attitudes, self-efficacy,
skills, perceived benefits/barriers, perceived susceptibility, perceived norms,
and outcome expectations as modifiable factors influencing HPV vaccination. Lay
health workers implemented the program in community clinics. A logic model of
change guided evaluation planning. We later adapted the outcome and intervention
content for parents of Hispanic adolescent males and changed the theme to Por
Nuestros Hijos (For Our Children). Throughout the development and adaptation
processes, we relied on theory, empirical evidence, and new data to make
decisions. Discussion: IM provided a systematic methodology for program
development and adaptation. Tasks in each step built upon one another integrating
findings from the literature, previous research, qualitative findings, and theory
to develop two educational programs for parents to increase HPV vaccination. The
systematic process allowed us to develop messages and materials targeting factors
beyond HPV knowledge or awareness to create behavior change.
PMID- 29963544
TI - Understanding Seasonal Changes to Improve Good Practices in Livestock Management.
AB - Background and Aim: Food quality control techniques based on process control
methods are increasingly adopted in livestock production systems to fulfill
increasing market's expectations toward competitiveness and issues linked to One
Health pillars (environment, animal, and human health). Control Charts allow
monitoring and systematic investigation of sources of variability in dairy
production parameters. These parameters, however, may be affected by seasonal
variations that render impractical, biased or ineffective the use statistical
control charts. A possible approach to this problem is to adapt seasonal
adjustment methods used for the analysis of economic and demographic seasonal
time series. The aim of the present work is to evaluate a seasonal decomposition
technique called X-11 on milk parameters routinely collected also in small farms
(fat, protein, and lactose content, solids-not-fat, freezing point, somatic cell
count, total bacterial count) and to test the efficacy of different seasonal
removal methods to improve the effectiveness of statistical control charting.
Method: Data collection was carried out for 3 years on routinely monitored bulk
tank milk parameters of a small farm. Seasonality presence was statistically
assessed on milk parameters and, for those parameters showing seasonality,
control charts for individuals were applied on raw data, on X-11 seasonally
adjusted data, and on data smoothed with a symmetric moving average filter.
Correlation of seasonally influenced parameters with daily mean temperature was
investigated. Results: Presence of seasonality in milk parameters was
statistically assessed for fat, protein, and solids-non-fat components. The X-11
seasonally-adjusted control charts showed a reduced number of violations (false
alarms) with respect to non-seasonally adjusted control chart (from 5 to 1
violation for fat, from 17 to 1 violation for protein, and from 9 to none
violation for solids-non-fat.). This result was achieved despite stricter control
chart limits: with respect to raw data charts, the interval of control chart
allowed variation (UCL-LCL) was reduced by 43% for fat, by 33.1% for protein, and
by 14.3% for solids-not-fat. Conclusions: X-11 deseasonalization of routinely
collected milk parameters was found to be an effective method to improve control
chart application effectiveness in farms and milk collecting centers.
PMID- 29963543
TI - Aerosol Sampling in a Hospital Emergency Room Setting: A Complementary
Surveillance Method for the Detection of Respiratory Viruses.
AB - This study aimed to evaluate environmental air sampling as an alternative form of
active surveillance for respiratory pathogens in clinical settings. Samples were
collected from three locations in the Emergency Department at Duke University
Hospital Systems from October 2017 to March 2018. Of the 44 samples collected, 12
were positive for known respiratory pathogens including influenza A, influenza D,
and adenovirus. Results suggest bioaerosol sampling may serve as a complement to
active surveillance in clinical settings. Additionally, since respiratory viruses
were detected in aerosol samples, our results suggest that hospital infection
control measures, including the use of N95 respirators, could be used to limit
the spread of infectious viruses in the air.
PMID- 29963546
TI - Competition Between Lemna minuta, Lemna minor, and Azolla filiculoides. Growing
Fast or Being Steadfast?
AB - A substantial number of Lemnaceae are invasive outside their natural distribution
area. Lemna minuta is considered invasive in several European countries, where it
can occur in the same habitat as invasive Azolla filiculoides and native Lemna
minor. In this study the presence, abundance and growth rates of all three
species were monitored across 24 natural ponds and in a series of mesocosms in
order to explore the importance of species invasiveness and habitat invisibility.
Field monitoring showed that the distribution of the three species of macrophytes
is heterogeneous in space and time. However, the data show no association of
nutrient or light levels with plant distribution. Indeed, using reciprocal
transplanting experiments it was demonstrated that all species are able to grow
in all ponds, even ponds where the species do not naturally occur. It is
concluded that distribution of L. minor, L. minuta, and A. filiculoides is not
limited by the prevailing physicochemical characteristics of the ponds during the
summer period. Remarkably, in these experiments A. filiculoides displayed the
highest RGR, and exerted a negative influence on growth rates and surface cover
of L. minor and L. minuta. Despite such apparent invasiveness, A. filiculoides
was relatively rare in the study area. Rather, the species most abundant was L.
minor which has the lowest RGR under field conditions in summer. Therefore, this
study shows that the invasiveness of the species during the summer months is not
necessarily reflected in the actual distribution pattern in natural ponds. In
fact, alien L. minuta and A. filiculoides are under-represented in the monitored
area. It is concluded that the interaction of several factors, including growth
under winter-conditions and/or dispersal after disturbances, is the major
determinant of the abundance and heterogeneous distribution of L. minor, L.
minuta, and A. filiculoides in the study area.
PMID- 29963545
TI - Self-Control in Intertemporal Choice and Mediterranean Dietary Pattern.
AB - Background: The Mediterranean Diet (hereinafter MD) is considered a healthy
dietary pattern. Adherence to this pattern can be assessed by means of the KIDMED
test by which individuals are assigned an index and classified into three groups
of adherence to MD: high, medium, and low. In addition, impulsivity or impatience
in intertemporal choice has been defined as a strong preference for small
immediate rewards over large delayed ones. Objective: This study examines the
relationship between dietary habits, specifically Mediterranean dietary pattern,
measured by the KIDMED index, and the exhibited impatience in intertemporal
choices, by means of the parameter k (discount rate of the hyperbolic discount
function). Methods: A sample of 207 university students answered a questionnaire
based on two tests: the KIDMED test, to assess the degree of adherence to MD, and
an intertemporal choice questionnaire, to assess impatience or impulsivity.
Individuals were grouped depending on their KIDMED score and then the discount
rate or impulsivity parameter was calculated for each group. Results: Discount
rates were inversely related to the degree of adherence to MD. The values of
overall k were 1.53, 1.91, and 3.71% for the groups exhibiting high, medium and
low adherence to MD, respectively. We also found higher k-values for larger
rewards (magnitude effect) in the three groups. Conclusion: High adherence to MD
is related to less steep time discounting, which implies less impulsivity (more
self-control) or lower discount rates. Conversely, low adherence to MD is related
to steeper time discounting, which implies impulsivity or higher discount rates.
These findings could be used to identify the target population where policy
interventions are needed in order to promote healthier diet habits.
PMID- 29963547
TI - pH-Responsive Particle-Liquid Aggregates-Electrostatic Formation Kinetics.
AB - Liquid-particle aggregates were formed electrostatically using pH-responsive
poly[2-(diethylamino)ethyl methacrylate] (PDEA)-coated polystyrene particles.
This novel non-contact electrostatic method has been used to assess the particle
stimulus-responsive wettability in detail. Video footage and fractal analysis
were used in conjunction with a two-stage model to characterize the kinetics of
transfer of particles to a water droplet surface, and internalization of
particles by the droplet. While no stable liquid marbles were formed, metastable
marbles were manufactured, whose duration of stability depended strongly on drop
pH. Both transfer and internalization were markedly faster for droplets at low
pH, where the particles were expected to be hydrophilic, than at high pH where
they were expected to be hydrophobic. Increasing the driving electrical potential
produced greater transfer and internalization times. Possible reasons for this
are discussed.
PMID- 29963548
TI - Hydrodeoxygenation of Bio-Derived Phenol to Cyclohexane Fuel Catalyzed by
Bifunctional Mesoporous Organic-Inorganic Hybrids.
AB - In this work, mesoporous silica materials SBA-15 functionalized with propyl/
phenyl-sulfonic acid group were synthesized and loaded with Pt to form
bifunctional catalysts. SAXRD, WAXRD, N2 adsorption-desorption, TEM techniques
were used to characterize the above bifunctional catalysts. These bifunctional
catalysts were applied to the reaction of hydrodeoxygenation (HDO) of bio-derived
phenol (PhOH) to produce cyclohexane fuel and showed very good catalytic
performances. There were strong synergies between the metal sites and the acid
sites on the bifunctional catalysts. This reaction of phenol HDO provides a model
system for the catalytic upgrading of biomass-derived fuel.
PMID- 29963549
TI - High-Performance Lithium-Sulfur Batteries With an IPA/AC Modified Separator.
AB - To inhibit the polysulfide-diffusion in lithium sulfur (Li-S) batteries and
improve the electrochemical properties, the commercial polypropylene (PP) was
decorated by an active carbon (AC) coating with lots of electronegative oxygenic
functional group of -OH. Owing to the strong adsorption of AC and the
electrostatic repulsion between the -OH and negatively charged polysulfide ions,
the Li-S batteries demonstrated a high initial discharge capacity of 1,656 mAh g
1 (approximately 99% utilization of sulfur) and the capacity can still remain at
830 mAh g-1 after 100 cycles at 0.2 C. Moreover, when the rate was increased to 1
C, the batteries could also possess a discharge capacity of 1,143 mAh g-1. The
encouraging cycling stability make clear that this facile approach can
successfully restrain the shuttle effect of polysulfides and make further
progress to the practical application of Li-S batteries.
PMID- 29963550
TI - New Anti-inflammatory Cyclopeptides From a Sponge-Derived Fungus Aspergillus
violaceofuscus.
AB - Three new cyclic peptides including a cyclic tetrapeptide (1), an aspochracin
type cyclic tripeptide sclerotiotide L (2) and a diketopiperazine dimer (3), have
been isolated from the ethyl acetate extract of a marine sponge-derived fungus
Aspergillus violaceofuscus. The structures of all compounds were unambiguously
elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopic data, MS/MS
experiments and chemical methods. Compounds 1 and 3 showed anti-inflammatory
activity against IL-10 expression of the LPS-induced THP-1 cells with inhibitory
rates of 84.3 and 78.1% respectively at concentration of 10 MUM.
PMID- 29963551
TI - Changes in the Neural and Non-neural Related Properties of the Spastic Wrist
Flexors After Treatment With Botulinum Toxin A in Post-stroke Subjects: An
Optimization Study.
AB - Quantifying neural and non-neural contributions to the joint resistance in
spasticity is essential for a better evaluation of different intervention
strategies such as botulinum toxin A (BoTN-A). However, direct measurement of
muscle mechanical properties and spasticity-related parameters in humans is
extremely challenging. The aim of this study was to use a previously developed
musculoskeletal model and optimization scheme to evaluate the changes of neural
and non-neural related properties of the spastic wrist flexors during passive
wrist extension after BoTN-A injection. Data of joint angle and resistant torque
were collected from 21 chronic stroke patients before, and 4 and 12 weeks post
BoTN-A injection using NeuroFlexor, which is a motorized force measurement device
to passively stretch wrist flexors. The model was optimized by tuning the passive
and stretch-related parameters to fit the measured torque in each participant. It
was found that stroke survivors exhibited decreased neural components at 4 weeks
post BoNT-A injection, which returned to baseline levels after 12 weeks. The
decreased neural component was mainly due to the increased motoneuron pool
threshold, which is interpreted as a net excitatory and inhibitory inputs to the
motoneuron pool. Though the linear stiffness and viscosity properties of wrist
flexors were similar before and after treatment, increased exponential stiffness
was observed over time which may indicate a decreased range of motion of the
wrist joint. Using a combination of modeling and experimental measurement,
valuable insights into the treatment responses, i.e., transmission of
motoneurons, are provided by investigating potential parameter changes along the
stretch reflex pathway in persons with chronic stroke.
PMID- 29963552
TI - FOXF1 Mediates Endothelial Progenitor Functions and Regulates Vascular Sprouting.
AB - Endothelial colony forming cells (ECFC) or late blood outgrowth endothelial cells
(BOEC) have been proposed to contribute to neovascularization in humans.
Exploring genes characteristic for the progenitor status of ECFC we have
identified the forkhead box transcription factor FOXF1 to be selectively
expressed in ECFC compared to mature endothelial cells isolated from the vessel
wall. Analyzing the role of FOXF1 by gain- and loss-of-function studies we
detected a strong impact of FOXF1 expression on the particularly high sprouting
capabilities of endothelial progenitors. This apparently relates to the
regulation of expression of several surface receptors. First, FOXF1
overexpression specifically induces the expression of Notch2 receptors and
induces sprouting. Vice versa, knock-down of FOXF1 and Notch2 reduces sprouting.
In addition, FOXF1 augments the expression of VEGF receptor-2 and of the arterial
marker ephrin B2, whereas it downmodulates the venous marker EphB4. In line with
these findings on human endothelial progenitors, we further show that knockdown
of FOXF1 in the zebrafish model alters, during embryonic development, the regular
formation of vasculature by sprouting. Hence, these findings support a crucial
role of FOXF1 for endothelial progenitors and connected vascular sprouting as it
may be relevant for tissue neovascularization. It further implicates Notch2, VEGF
receptor-2, and ephrin B2 as downstream mediators of FOXF1 functions.
PMID- 29963553
TI - Advanced Plant-Based Glycan Engineering.
AB - With respect to biomanufacturing, glycosylation is one of the most addressed post
translational modifications, since it is well-known that the attachment of sugar
residues efficiently affects protein homogeneity and functionality. Much effort
has been taken into engineering various expression systems to control
glycosylation and to generate molecules with targeted sugar profiles.
Nevertheless, engineering of N- and O-linked glycans on well-established
expression systems remains challenging. On the one side the glycosylation
machinery in mammalian cells is hard to control due to its complexity. Most
bacteria, on the other side, completely lack such glycan formations, and in
general exhibit fundamental differences in their glycosylation abilities. Beyond
that, plants generate complex N-glycans typical of higher eukaryotes, but simpler
than those produced by mammals. Paradoxically, it seems that the limited
glycosylation capacity of plant cells is an advantage for specific glycan
manipulations. This review focuses on recent achievements in plant glycan
engineering and provides a short outlook on how new developments (in synthetic
biology) might have a positive impact.
PMID- 29963555
TI - Global Provisioning of Red Meat for Flexitarian Diets.
AB - Although not always labeled as such, flexitarianism is the default lifestyle for
much of the world, whereby meals based on plant materials provide the bulk of
people's calories. The rich nutrition of meat and animal products is often the
lynchpin of these diets, even when only consumed occasionally. It provides forms
and concentrations of essential proteins, lipids, and micronutrients that are
otherwise scarce. However, the production of this meat is resource intensive. It
requires large quantities of arable land and water, and typically has lower
conversion efficiency of farm inputs to edible outputs compared with crops,
poultry, aquaculture, dairy, and eggs. An additional complication is that the
quantity of ancillary products produced during slaughterhouse operations is large
and underutilized. Each year, approximately 190 million metric tons (MMT) of red
meat, including pork, lamb, sheep, veal, beef, and goats are produced globally,
half of which will be consumed by less than 25% of the population living in
developed countries. With demand for meat expected to exceed 376 MMT by 2030, an
increase in the adoption of plant-based diets presents an opportunity for the
world to re-evaluate how meat can be sustainably produced, with greater emphasis
on animal welfare, nutritional value, product safety, better utilization, and
distribution channels. In this article we consider the role meat plays in the
modern diet, its production and consumption, opportunities to improve utilization
of the animal, the benefits of incorporating a diverse range of red meat into
diets, and the strategies that the meat industry should consider in response to
flexitarianism.
PMID- 29963556
TI - The role of telemedicine in postoperative care.
AB - Telemedicine has become one of the most rapidly-expanding components of the
health care system. Its adoption has afforded improved access to care, greater
resource efficiency, and decreased costs associated with traditional office
visits and has been well established in a wide array of fields. Telemedicine has
been adopted in several domains of surgical care. In recent years, the role of
telemedicine in postoperative care has caught attention as it has demonstrated
excellent clinical outcomes, enhanced patient satisfaction, increased
accessibility along with reduced wait times, and cost savings for patients and
health care systems. In this narrative review, we describe the history of
telemedicine, its adoption in the field of surgery and its various modalities,
its use in the postoperative setting, and the potential benefits to both patients
and healthcare systems. As telemedicine continues to emerge as a powerful tool
for health care delivery, we also discuss several barriers to its widespread
adoption as well as the future utility of telemedicine in postoperative care.
PMID- 29963554
TI - Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical
Models.
AB - Within the last years, the use of stem cells (embryonic, induced pluripotent stem
cells, or hematopoietic stem cells), Progenitor cells (e.g., endothelial
progenitor cells), and most intensely mesenchymal stromal cells (MSC) has emerged
as a promising cell-based therapy for several diseases including nephropathy. For
patients with end-stage renal disease (ESRD), dialysis or finally organ
transplantation are the only therapeutic modalities available. Since ESRD is
associated with a high healthcare expenditure, MSC therapy represents an
innovative approach. In a variety of preclinical and clinical studies, MSC have
shown to exert renoprotective properties, mediated mainly by paracrine effects,
immunomodulation, regulation of inflammation, secretion of several trophic
factors, and possibly differentiation to renal precursors. However, studies are
highly diverse; thus, knowledge is still limited regarding the exact mode of
action, source of MSC in comparison to other stem cell types, administration
route and dose, tracking of cells and documentation of therapeutic efficacy by
new imaging techniques and tissue visualization. The aim of this review is to
provide a summary of published studies of stem cell therapy in acute and chronic
kidney injury, diabetic nephropathy, polycystic kidney disease, and kidney
transplantation. Preclinical studies with allogeneic or xenogeneic cell therapy
were first addressed, followed by a summary of clinical trials carried out with
autologous or allogeneic hMSC. Studies were analyzed with respect to source of
cell type, mechanism of action etc.
PMID- 29963558
TI - Mobile health considerations for kidney disease and transplantation.
PMID- 29963557
TI - Assessing operating room turnover time via the use of mobile application.
AB - Background: Improving operating room (OR) utilization is crucial to hospitals.
This study examines the effectiveness of a mobile application co-developed with
hospital staff to track OR turnover time (TOT). Methods: An Android-based app,
named ORTimer, was used by staff in two OR units (GI-Lab and D-Core) of
Greenville Memorial Hospital (GMH) in South Carolina. The staff used the app to
record milestones and note delay reasons (if applicable). A total of 1,782
turnover observations from the GI-Lab and 694 turnover observations from the D
Core were collected for the study. Using data collected from the app and
additional information from GMH's electronic medical record system, a two-sample
proportionality test was conducted to test the hypothesis that the use of the app
improved OR turnover performance (i.e., the TOT is equal to or less than the
allotted time). Results: The result of the hypothesis test indicates that a
higher percentage of observations in the GI-Lab and D-Core met their turnover
target time when the ORTimer app was used. Additionally, multiple regression
analysis was used to identify significant factors that contribute to prolonged OR
TOT and to estimate their impacts. Conclusions: The app serves as both a visual
management tool as well as a TOT data collection tool. By identifying barriers to
the on-time completion of the turnaround, the app allows for continuous
improvement of the turnover process.
PMID- 29963559
TI - Providing support to pregnant women and new mothers through moderated WhatsApp
groups: a feasibility study.
AB - Background: Group-based health services can improve maternal and newborn health
outcomes. Group antenatal care and participatory learning and action cycles (PLA)
with women's groups have been cited by the WHO as health systems interventions
that can lead to improvements in adherence to care and health outcomes in
pregnancy and the postpartum period. Methods: We used a mixed-methods approach to
assess the feasibility of a light touch group-based support intervention using
the WhatsApp text-messaging platform. Pregnant women were enrolled at Jacaranda
Health (JH), a maternity center in peri-urban Kiambu County, Kenya. Their phone
numbers were added to WhatsApp groups consisting of participants with similar
estimated due dates. The WhatsApp group administrator was a JH employee.
Acceptability, demand, implementation, and practicality of this service were
evaluated through in-depth interviews (IDIs), surveys, chart review, and analysis
of group chats. Limited analysis of program efficacy (ANC visits, any PNC, and
post-partum family planning uptake) was assessed by comparing participant data
collected through chart review using a concurrent comparison of the general JH
patient population. Results: Fifty women (88%) of 57 eligible women who were
approached to participate enrolled in the study. Five WhatsApp groups were
created. A total of 983 messages were exchanged over 38 weeks. No harms or
negative interactions were reported. Participants reported several benefits.
Participants had differing expectations of the level of the group administrator's
activity in the groups. ANC and PNC attendance were in line with the hospital's
metrics for the rest of JH's patient population. Higher rates of postpartum long
acting reversible contraception (LARC) uptake were observed among participants
relative to the general patient population. Conclusions: A moderated mobile-based
support group service for pregnant women and new mothers is safe and feasible.
Additional research using experimental designs to strengthen evidence of the
effectiveness of the support intervention is warranted.
PMID- 29963561
TI - Predictors of health anxiety during pregnancy.
AB - Background: The internet has become a quick, easy and accessible source for
health-related information. Women are more likely to search for health
information online and this likelihood increases further during pregnancy.
Searching online for health-related information can have both positive and
negative impacts upon levels of health anxiety during pregnancy. This research
initially explored how health impacts heath anxiety during pregnancy. Secondly,
the sources of offline support that predict health anxiety and thirdly, how
online health seeking behaviour predicts health anxiety. Methods: The sample
consisted of 159 pregnant women who completed an online questionnaire to
investigate significant predictors of health anxiety during pregnancy. Results:
Multiple regression analyses showed health anxiety increased during pregnancy
when medical complications had been experienced in a previous pregnancy and if
under medical treatment for a non-pregnancy related condition. Interestingly,
health anxiety was not affected by medical complications in the current
pregnancy. Knowing when you have had enough information and repeating searches
were significant predictors of levels of health anxiety, whereas using the same
or different sources was not. Conclusions: For many the internet is a convenient
platform for information however the information is not always accurate, reliable
or helpful. Relevant health care professionals should continue to sign-post
pregnant women to validated health information websites with the aim to reassure
women during pregnancy. Further research in this area would benefit from
exploring how women use the internet when pregnant and devising guidelines which
can be followed and recommended when doing so.
PMID- 29963560
TI - PTSD Coach around the world.
AB - Posttraumatic stress disorder (PTSD) is a global public health problem.
Unfortunately, many individuals with PTSD do not receive professional care due to
a lack of available providers, stigma about mental illness, and other concerns.
Technology-based interventions, including mobile phone applications (apps) may be
a viable means of surmounting such barriers and reaching and helping those in
need. Given this potential, in 2011 the U.S Veterans Affairs National Center for
PTSD released PTSD Coach, a mobile app intended to provide psycho-education and
self-management tools for trauma survivors with PTSD symptoms. Emerging research
on PTSD Coach demonstrates high user satisfaction, feasibility, and improvement
in PTSD symptoms and other psychosocial outcomes. A model of openly sharing the
app's source code and content has resulted in versions being created by
individuals in six other countries: Australia, Canada, The Netherlands, Germany,
Sweden, and Denmark. These versions are described, highlighting their significant
adaptations, enhancements, and expansions to the original PTSD Coach app as well
as emerging research on them. It is clear that the sharing of app source code and
content has benefited this emerging PTSD Coach community, as well as the
populations they are targeting. Despite this success, challenges remain
especially reaching trauma survivors in areas where few or no other mental health
resources exist.
PMID- 29963562
TI - Machine learning for detection of lymphedema among breast cancer survivors.
AB - Background: In the digital era when mHealth has emerged as an important venue for
health care, the application of computer science, such as machine learning, has
proven to be a powerful tool for health care in detecting or predicting various
medical conditions by providing improved accuracy over conventional statistical
or expert-based systems. Symptoms are often indicators for abnormal changes in
body functioning due to illness or side effects from medical treatment. Real-time
symptom report refers to the report of symptoms that patients are experiencing at
the time of reporting. The use of machine learning integrating real-time patient
centered symptom report and real-time clinical analytics to develop real-time
precision prediction may improve early detection of lymphedema and long term
clinical decision support for breast cancer survivors who face lifelong risk of
lymphedema. Lymphedema, which is associated with more than 20 distressing
symptoms, is one of the most distressing and dreaded late adverse effects from
breast cancer treatment. Currently there is no cure for lymphedema, but early
detection can help patients to receive timely intervention to effectively manage
lymphedema. Because lymphedema can occur immediately after cancer surgery or as
late as 20 years after surgery, real-time detection of lymphedema using machine
learning is paramount to achieve timely detection that can reduce the risk of
lymphedema progression to chronic or severe stages. This study appraised the
accuracy, sensitivity, and specificity to detect lymphedema status using machine
learning algorithms based on real-time symptom report. Methods: A web-based study
was conducted to collect patients' real-time report of symptoms using a mHealth
system. Data regarding demographic and clinical information, lymphedema status,
and symptom features were collected. A total of 355 patients from 45 states in
the US completed the study. Statistical and machine learning procedures were
performed for data analysis. The performance of five renowned classification
algorithms of machine learning were compared: Decision Tree of C4.5, Decision
Tree of C5.0, gradient boosting model (GBM), artificial neural network (ANN), and
support vector machine (SVM). Each classification algorithm has certain user
definable hyper parameters. Five-fold cross validation was used to optimize these
hyper parameters and to choose the parameters that led to the highest average
cross validation accuracy. Results: Using machine leaning procedures comparing
different algorithms is feasible. The ANN achieved the best performance for
detecting lymphedema with accuracy of 93.75%, sensitivity of 95.65%, and
specificity of 91.03%. Conclusions: A well-trained ANN classifier using real-time
symptom report can provide highly accurate detection of lymphedema. Such
detection accuracy is significantly higher than that achievable by current and
often used clinical methods such as bio-impedance analysis. Use of a well-trained
classification algorithm to detect lymphedema based on symptom features is a
highly promising tool that may improve lymphedema outcomes.
PMID- 29963563
TI - Experiential learning in oral health education.
AB - Experiential learning is an innovative learning method that knowledge is gained
through experience. The aim of this paper was to review the application of
experiential learning in health education and suggest an oral health education
program using experiential learning. Experiential learning has been used in the
past successfully in health education mostly in university curricula. In oral
health education, its use is limited and without following a comprehensive
structure. An experiential learning oral health education program, implemented in
the classroom by a trained teacher, is proposed to be integrated in the school's
curriculum. Initially, using brainstorming students express their opinions and
feelings toward oral health. Then, students are allocated to working groups to
develop oral health projects. The outcome of these projects is presented in the
classroom to their peers through role playing, posters, songs, games, etc.,
Finally, a discussion is stimulated by the teacher to encourage children to
express their feelings about oral health issues and thus experientially recognize
the importance of oral health. Experiential learning has been effectively used in
health education and can be a successful method for oral health education. For
optimal results, a predetermined experiential method structure has to be
followed.
PMID- 29963564
TI - Effectiveness of training program on attitude and practice of infection control
measures among nurses in two teaching hospitals in Ogun State, Nigeria.
AB - BACKGROUND: Infection control has become a major concern in the health-care
system and health-care workers, particularly nurses are at high risk of
infection. This study, therefore, examined the effect of a training program on
attitude and practice of infection control among nurses in two tertiary hospitals
in Ogun State, Nigeria. MATERIALS AND METHODS: This study adopted a pretest
posttest quasi-experimental design. The sample consisted of 87 participants. The
experimental group consisted of 42 registered nurses from Babcock University
Teaching Hospital, Ogun state, Nigeria, while the control group consisted of 45
registered nurses from Olabisi Onabanjo University Teaching Hospital, Sagamu,
Nigeria. The instrument for data collection was attitude toward components of
infection control questionnaire (r = 72) and practice of infection control
questionnaire (r = 76). Data were analyzed using SPSS version 21.0 (SPSS Inc.
Chicago IL, USA). RESULTS: Findings showed that the mean age in the experimental
group was 34.92 +/- 8.9 while the control group was 47.43 +/- 6.6. The average
years of experience for the experimental group were 10.42 +/- 9.9 while that of
the control group were 21.89 +/- 8.7. Responses on attitude showed that 30
participants (69%) had positive attitude in the experimental group compared to 21
participants (46.7%) in the control group. The mean difference was 4.02.
Significant difference was observed between mean attitude score of participants
in the experimental group and control group (P = 0.03), between mean practice
score (P = 0.001), and between self-reported and observed practices (P = 0.000).
CONCLUSION: The training was effective in improving attitude and practice of
infection control. Adequate provision of structured training programs on
infection control measures is recommended.
PMID- 29963565
TI - Hospitals reorientation towards health promotion: A qualitative study of barriers
to and strategies for implementation of health promotion in hospitals of Isfahan,
Iran.
AB - CONTEXT: The World Health Organization (WHO) has emphasized the need for
reorientation of hospitals toward health promotion (HP). AIMS: This study
explores health-care professionals' perception of barriers and strategies to
implementing HP in educational hospitals of Isfahan Province in Iran. SETTINGS
AND DESIGN: The study settings included four selective educational hospitals and
the Treatment Administration affiliation to the Isfahan University of Medical
Sciences. SUBJECTS AND METHODS: A qualitative content analysis approach was
employed in this study, with semi-structured in-depth interviews. Eighteen
participants from hospital and accreditation managers, nurses, community medicine
specialist, and directors of health-care quality improvement and accreditation
participated in the study by purposeful sampling method. The data were analyzed
using content analysis method. RESULTS: The barriers can be categorized into the
following areas: (1) barriers associated with patient and community, (2) barriers
associated with health-care professionals, (3) barriers associated with the
organization, and (4) external environment barriers. The results were summarized
into four categories as strategies, including: (1) marketing the plan, (2)
identifying key people and training, (3) phasing activities and development of
feasible goals, and (4) development of strategic goals of health promoting
hospitals and supportive policies. CONCLUSIONS: The interactions of individual,
organizational, and external environmental factors were identified as barriers to
implementation of HP in hospitals. To hospital reorientation toward HP,
prioritizing the barriers, and using the proposed strategies may be helpful.
PMID- 29963566
TI - Effect of spiritual care education on postpartum stress disorder in women with
preeclampsia.
AB - INTRODUCTION: Posttraumatic stress disorder is an anxiety disorder that occurs
after exposure to an event that causes injury or threat. The prevalence of
preeclampsia was reported to be 28%. Considering the significant role of
spiritual care in physical and psychological outcomes of patients, this study was
conducted to determine "the effect of spiritual care education on postpartum
stress disorder in women with preeclampsia". MATERIALS AND METHODS: In this
randomized clinical trial, 72 pregnant women (36 in each group) were selected in
a convenient way between the ages of 34 and 38 weeks who had preeclampsia and
admitted to two public hospitals in Mashhad. The questionnaires such as Duke
University Religion Index, DASS 21, the Posttraumatic Stress Disorder Checklist
(PCL), and Prenatal Posttraumatic Stress Questionnaire (PPQ) were used at the
beginning in two groups. In the intervention group, first, women were educated
each day based on Richards and Bergin's pattern, in three sessions, which lasted
45-60 min. The control group also received routine cares. All units completed
questionnaires such as Prenatal Posttraumatic Stress Questionnaire (PPQ) at the
4th-6th postpartum period. Results were analyzed by independent t-test, Mann
Whitney test, Chi-square test, and SPSS version 16. RESULTS: The mean change
score of postpartum stress disorder in the intervention and control groups was
different after intervention (P = 0.001). CONCLUSION: Providing spiritual care to
pregnant mothers with preeclampsia reduces their risk of postpartum stress
disorder. Therefore, this kind of care as an effective intervention is included
in the routine care of this group with high-risk pregnancies.
PMID- 29963567
TI - The effect of mindfulness program on general health of patients undergoing
hemodialysis.
AB - INTRODUCTION: Patients undergoing hemodialysis have a low level of health and
mindfulness technique in mind-body medicine is used to help patients with chronic
illness. Therefore, this clinical trial was conducted to determine the effect of
the mindfulness program on the general health of patients undergoing treatment
with hemodialysis. METHODS: Sixty hemodialysis patients were selected through the
convenient method and randomly divided into experimental and control groups. Both
groups completed demographic information questionnaire and general health
questionnaire. Then, the experimental group received 8 sessions of mindfulness
training and the control group received 8 sessions of education in relation to
end-stage renal disease and hemodialysis. Educational sessions were performed for
both groups in the second 30 min after hemodialysis for 1 h in six individual
sessions and two 1.5 h group sessions. Immediately after and 1 month after the
intervention, the General Health Questionnaire was completed by both groups.
RESULTS: Analysis of the findings showed no significant differences between the
mean score of general health disorder and its subscales before the intervention
in to two groups (P > 0.05). Nevertheless, after intervention in the experimental
group, the mean of general health disorder score decreased from 44.17 +/- 12.32
to 21.9 +/- 6.4 and 1 month after the intervention, the mean score of this score
was 23.6 +/- 6.2. The mean score of physical symptoms, anxiety and sleep
disorder, social functioning deficiency, and depression were also significantly
lower in the experimental group immediately after intervention and 1 month after
the intervention; however, there were no significant differences between the mean
of this score immediately and 1 month after the intervention. In addition, the
mean score of general health disorder changes immediately and 1 month after the
intervention in the experimental group was significantly more than the control
group. In the control group, there was no significant difference between the mean
score of general health disorder and its subscales before, immediately, and 1
month after the intervention (P > 0.05). CONCLUSIONS: The results of this
research showed that mindfulness has been effective in reducing physical and
anxiety symptoms, sleep disorder, social dysfunction, and depression symptoms.
Therefore, the use of mindfulness as a complementary treatment can improve the
general health level in these patients.
PMID- 29963568
TI - Substance use among outdoor treatment-seeking patients with mental illness: A
case-control study from a tertiary care hospital of northern India.
AB - BACKGROUND: Substance abuse and mental disorder often coexist and may cause
several consequences in sociooccupational functioning and health care and
management. Indian data are sparse in this area. OBJECTIVES: The aim of the study
was to examine the sociodemographic profile, pattern, and prevalence of alcohol
and substance use among person suffering with mental illness and to compare with
those without mental illness. METHODS: A total of 80 treatment-seeking patients
with mental illness and 80 nontreatment seeking healthy accompanying persons were
assessed for current substance use. Mental illness was screened using Structured
Clinical Interview for DSM-IV Axis I Disorders and the diagnosis was made as per
DSM IV, semi-structured sociodemographic pro forma was also applied. The data
collected were analyzed using the Chi-square and Student's t-test. RESULTS:
Substance use was found 2.5 times higher among cases (56.2%) than controls
(22.5%). Substance-using participants comprised mainly males belonging to rural
residence. The substance using cases were more unmarried, less educated, poorer
economically, and more nuclear family structures that substance-using controls.
When compared with non-substance using cases, cases with substance use had more
males than females and lower education. Although both groups were almost similar
in term of marital status, family structure, residence, and socioeconomic status.
Among both groups, most common substance use was tobacco, followed by alcohol and
cannabis. Although all the substances were more prevalent among cases than
controls. The prevalence of any substance use was highest among cases with
psychotic disorder (77.3%), followed by unipolar depression (62.5%), bipolar
affective disorder (41.7%), and anxiety disorders (21.4%). Tobacco and cannabis
use was most prevalent among cases suffering with psychotic disorders, whereas
alcohol use was most prevalent among cases suffering with unipolar depression.
CONCLUSIONS: Mentally ill individuals are vulnerable to develop substance use,
thus they are doubly jeopardized. The susceptibility of these individuals stem
from lesser insight, need for stimulation, to decrease the anhedonia induced by
psychoactive medicines and poor awareness hence this group of individuals has
several health and social consequences; therefore, they require due attention. A
better care, support, and education are needed for substance using patients with
mental illness to improve their prognosis and also help in their appropriate
rehabilitation.
PMID- 29963569
TI - The effect of nutrition education course on awareness of obese and overweight
female 1st-year High School students of Isfahan based on transtheoretical model
of behavioral change.
AB - BACKGROUND/AIM: Today, the problem of obesity is a chronic condition that affects
all age groups in developed and developing countries. Since adolescence is a
transitional period and behavioral patterns formed in this period affect people
in their adult years, attention to obesity and extra weight in this age group is
more important than other groups. Therefore, this study aims to investigate the
effects of nutrition education course on awareness of female 1st-year high school
students of Isfahan based on transtheoretical model ( TTM) of behavioral change.
MATERIALS AND METHODS: In this semi-empirical study, 64 female 1st-year high
school students with weight problem were selected using nonpercent stratified
sampling and divided into two control and test groups. Data gathering was carried
out using researcher-made nutrition awareness and stages of change questionnaire
whose validity and reliability was confirmed. Participants in the test group
participated in a 2-month education with sessions every 2 weeks and received one
brochure and 3 educational massages each week. Data were analyzed using
independent t-test and Mann-Whitney test. RESULTS: The results showed that the
average nutrition awareness score of students in test group was significantly
higher than control group after intervention. Students in test group were also in
higher stages of change compared to control group after intervention. CONCLUSION:
The results show that TTM was effective in changing nutritional behavior in
students.
PMID- 29963570
TI - Evaluation of an educational intervention based on health belief model on beta
thalassemia carrier and final suspects couples.
AB - INTRODUCTION: Beta-thalassemia is the most severe form of thalassemia major in
which where the person needs regular blood transfusions and medical cares. The
genetic experiment of prenatal diagnosis (PND) has been effective in the
diagnosis of fetus with thalassemia major. This study was aimed to evaluate
educational interventions on perceived susceptibility, perceived severity,
perceived benefits, perceived barriers, cues to action and self-efficacy in beta
thalassemia carriers and suspected couples on doing a PND genetic test in
Andimeshk. MATERIALS AND METHODS: In this quasi-experimental study, 224 beta
thalassemia carriers and suspected couples were randomly assigned to intervention
and control groups. The data were collected using a researcher-made validated
questionnaire using the self-administrated method. Before the intervention,
questionnaires for both groups were completed, and then, an educational
intervention was done for the intervention group during a month in four sessions
for 30 min. After 2 months, the questionnaire was completed again by both groups.
Data were analyzed using SPSS software version 20. RESULTS: There was no
significant difference in the mean score of health belief model (HBM) variables
and behavior between intervention and control groups before intervention (P <
0.05). However, after the educational intervention, the significant statistical
difference in the mean score of perceived sensitivity, perceived severity,
perceived benefits, perceived barriers, guidance for action, self-efficacy, and
behavior of PND beta-thalassemia genetic tests was observed between the
intervention and control groups. (P < 0.001). CONCLUSION: Educational programs
based on HBM can increase HBM constructs, behavior, and self-efficacy of beta
thalassemia carrier couples for doing beta-thalassemia PND.
PMID- 29963571
TI - Oral health comparison between pregnant and nonpregnant women: A comment on Payal
et al.
PMID- 29963572
TI - Role of intellectual capital on creation of innovation capabilities in HIS and
computer units.
AB - INTRODUCTION: Simultaneously along with information technology progress,
knowledge has considered as a fundamental base for economic growth for the time
being. In today's knowledge-based economy, production and exploitation of
knowledge play the main roles in the process of wealth creation. The current
revolution in information technology has given new light to the importance of
knowledge such that it has now become the base of economy in today's world. In
today's knowledge-based economy, production and exploitation of knowledge play
the main roles in the process of wealth creation. Considering key contributions
of knowledge management in competitiveness of organizations and their entry into
global arenas, this study sought to evaluate the impact of different aspects of
intellectual property on innovations in computer and health information system
(HIS) units at selected medical center in the city of Isfahan during 2015.
OBJECTIVES: The present study seeks to evaluate the impact of different aspects
of intellectual property on innovations in computer and HIS units at selected
medical centers in the city of Isfahan during 2015 (2015). SETTINGS AND DESIGN:
Population of this research includes staff working in computer and HIS units of
10 medical centers. Data were collected using a questionnaire made by the
researcher. A written questionnaire (also referred to as self-administered
questionnaire) is a data collection tool in which written questions are presented
that are to be answered by study individuals, where for the case of the present
study include staff members working at computer and HIS units of 10 medical
centers. MATERIALS AND METHODS: In the first stage, medical factors were
determined by experts of Isfahan University of Medical Sciences as intellectual
property. Factors were then distributed randomly among 100 employees during a
survey, after considering their validity and reliability. STATISTICAL ANALYSIS:
Descriptive and inferential statistics were used for data analysis. RESULTS: Data
analysis showed that innovation is one of the most important indicators of
intellectual capital in computer and HIS units of medical centers and has a
higher than average importance. CONCLUSIONS: The results of this study, in
addition to providing guidelines in the management of intellectual capital in
Isfahan province hospitals, can be used as a model for improving innovation in
hospitals and understanding various factors affecting organizational innovation.
PMID- 29963573
TI - Experience of people with physical disability: Mobility needs during earthquakes.
AB - BACKGROUND: People with physical disability are vulnerable in disasters because
of their mobility limitations. They are unable to escape from hazards and their
needs have been somewhat neglected in planning and relief measures. AIM: This
study aimed to identify the mobility needs of people with physical disability
during earthquakes across different provinces of Iran. MATERIALS AND METHODS: A
qualitative study was conducted using 18 semi-structured interviews with
participants who had a kind of mobility disability. The participants, across six
provinces of Iran who had experienced an earthquake, were selected by purposive
sampling in two ways of snowballing and maximum variation in 2017. Data were
analyzed thematically assisted by MAXQDA 10 software. RESULTS: The mobility needs
included house and workplace adaptation, spare assistive devices, easy access to
vehicles, special facilities for emergency evacuation, adaptation and
accessibility of shelters, adapted bathroom and toilet, and transferring by
others. CONCLUSION: By considering needs and experiences of people with physical
disability in disaster planning, appropriate interventions can be arranged to
promote the level of response in disasters. Such measures can have a significant
role in maintaining the lives and health of such people.
PMID- 29963574
TI - Satisfaction level among patients visiting a rural dental institution toward
rendered dental treatment in Haryana, North India.
AB - BACKGROUND: To provide quality care to the patient's perspective and patient
satisfaction are two major multidimensional concepts. In India, patient
satisfaction with dental services has received only minor attention as the
importance of the teeth is always neglected. OBJECTIVE: To assess the
satisfaction level among patients toward dental treatment rendered at an academic
institution. MATERIALS AND METHODS: A cross-sectional study was conducted among
474 voluntary camp patients visiting Department of Public Health Dentistry, Swami
Devi Dyal Hospital and Dental College, Barwala, using a 14-item closed ended
questionnaire which included demographic details, attitude, and practices of the
participants and their satisfaction level to the treatment rendered to them was
graded as highly satisfied, satisfied, and not satisfied. The data were analyzed
using SPSS version 18 which covered both descriptive and inferential statistics.
RESULTS: Curative and preventive treatment was mostly required in younger age
groups whereas extraction and prosthetic rehabilitation were found to be present
in older age groups. Lack of education and awareness was the most common reason
behind not seeking treatment. Majority of the participants were satisfied with
the treatment rendered and were found to be statistically significant with
visiting and referrals (P < 0.01). CONCLUSION: Imparting proper and appropriate
information regarding the dental treatment will definitely change the attitude of
the patients, thus help in raising the satisfaction levels.
PMID- 29963575
TI - Developing knowledge and clinical competency in a respiratory system-based
practice of final-year medical students through a novel structured bedside
teaching module.
AB - BACKGROUND: Respiratory diseases are a major cause of mortality and morbidity
worldwide. A sound knowledge of management of respiratory diseases is thus very
vital. The clinical exposure of undergraduate medical students is limited to 2
weeks in pulmonary medicine. We hypothesized that the short duration of posting
can be best utilized by developing need-based modules for bedside teaching. AIMS:
This study aimed to determine gain in knowledge and skills of final-year medical
students in diagnosis and management of common pulmonary diseases and assess
students' perception of the module. METHODS: A one-group pretest-posttest quasi
experimental study design enrolled a convenience sample of 48 final-year medical
students. Twenty-four students were posted at a given time for the bedside
clinical posting in pulmonary medicine between August 2013 and November 2013.
These students were divided randomly into two groups of 12 students each. All
students consented to be part of the study. Two trained faculty taught in
rotation. The bedside teaching module was prepared by Delphi technique and
curriculum was based on Kern's six-step approach. History taking, physical
examination, tuberculosis, chronic obstructive pulmonary disease, asthma, lung
cancer, chest X-rays, and spirometry were taught. Students were administered pre-
and post-test questionnaires to assess knowledge, while Objective Structured
Clinical Examination assessed skills. Students' feedback questionnaire evaluated
the teaching module. A two-tailed paired sample t-test assessed mean gain in
knowledge and skills. Effect size was calculated by Cohen's d, while Cronbach's
alpha estimated the reliability testing of perception questionnaire. Statistical
analysis was performed using statistical software package IBM SPSS version 23.
RESULTS: Mean pre- and posttest knowledge scores were 12.46 (8.09) and 43.17
(10.7), respectively, P = 0.001. Mean pre- and posttest skills scores were 7.00
(4.76) and 24.79 (3.31), respectively, P = 0.001, and Cohen's d showed large
effect size. Most students stated that the module enhanced their clinical skills,
helped to understand difficult material, and promoted inquiry and thinking.
Cronbach's alpha for perception questionnaire was 0.854. CONCLUSIONS: Structured
bedside teaching module in pulmonary medicine improved the knowledge and skills
of undergraduate medical students. The contents and various teaching
methodologies were evaluated positively.
PMID- 29963576
TI - Putting underspecification in context: ERP evidence for sparse representations in
morphophonological alternations.
AB - Numerous studies have shown evidence for a sparse lexicon in speech perception,
often in the guise of underspecification, where certain information is omitted in
the specification of phonological forms. While previous work has made a good case
for underspecifying certain features of single speech sounds, the role of
phonological context in underspecification has been overlooked. Contextually
mediated underspecification is particularly relevant to conceptualizations of the
lexicon, as it is couched in item-specific (as opposed to phoneme-specific)
patterning. In this study, we present behavioral and ERP evidence that
surrounding phonological context may trigger underspecified lexical forms, using
regular morphophonological alternations in English.
PMID- 29963577
TI - Subspace-based resolution-enhancing image reconstruction method for few-view
differential phase-contrast tomography.
AB - It is well known that properly designed image reconstruction methods can
facilitate reductions in imaging doses and data-acquisition times in tomographic
imaging. The ability to do so is particularly important for emerging modalities,
such as differential x-ray phase-contrast tomography (D-XPCT), which are
currently limited by these factors. An important application of D-XPCT is high
resolution imaging of biomedical samples. However, reconstructing high-resolution
images from few-view tomographic measurements remains a challenging task due to
the high-frequency information loss caused by data incompleteness. In this work,
a subspace-based reconstruction strategy is proposed and investigated for use in
few-view D-XPCT image reconstruction. By adopting a two-step approach, the
proposed method can simultaneously recover high-frequency details within a
certain region of interest while suppressing noise and/or artifacts globally. The
proposed method is investigated by the use of few-view experimental data acquired
by an edge-illumination D-XPCT scanner.
PMID- 29963578
TI - Convolutional neural network-based image enhancement for x-ray percutaneous
coronary intervention.
AB - Percutaneous coronary intervention (PCI) uses x-ray images, which may give high
radiation dose and high concentrations of contrast media, leading to the risk of
radiation-induced injury and nephropathy. These drawbacks can be reduced by using
lower doses of x-rays and contrast media, with the disadvantage of noisier PCI
images with less contrast. Vessel-edge-preserving convolutional neural networks
(CNN) were designed to denoise simulated low x-ray dose PCI images, created by
adding artificial noise to high-dose images. Objective functions of the designed
CNNs have been optimized to achieve an edge-preserving effect of vessel walls,
and the results of the proposed objective functions were evaluated qualitatively
and quantitatively. Finally, the proposed CNN-based method was compared with two
state-of-the-art denoising methods: K-SVD and block-matching and 3D filtering.
The results showed promising performance of the proposed CNN-based method for PCI
image enhancement with interesting capabilities of CNNs for real-time denoising
and contrast enhancement tasks.
PMID- 29963579
TI - Quantitative 3-D head ultrasound measurements of ventricle volume to determine
thresholds for preterm neonates requiring interventional therapies following
posthemorrhagic ventricle dilatation.
AB - Dilatation of the cerebral ventricles is a common condition in preterm neonates
with intraventricular hemorrhage. This posthemorrhagic ventricle dilatation
(PHVD) can lead to lifelong neurological impairment through ischemic injury due
to increased intracranial pressure, and without treatment can lead to death. Two
dimensional ultrasound (US) through the fontanelles of the patients is serially
acquired to monitor the progression of PHVD. These images are used in conjunction
with clinical experience and physical exams to determine when interventional
therapies such as needle aspiration of the built up cerebrospinal fluid
(ventricle tap, VT) might be indicated for a patient; however, quantitative
measurements of the ventricles size are often not performed. We describe the
potential utility of the quantitative three-dimensional (3-D) US measurements of
ventricle volumes (VVs) in 38 preterm neonates to monitor and manage PHVD.
Specifically, we determined 3-D US VV thresholds for patients who received VT in
comparison to patients with PHVD who resolve without intervention. In addition,
since many patients who have an initial VT will receive subsequent interventions,
we determined which PHVD patients will receive additional VT after the initial
one has been performed.
PMID- 29963580
TI - Development of a pulmonary imaging biomarker pipeline for phenotyping of chronic
lung disease.
AB - We designed and generated pulmonary imaging biomarker pipelines to facilitate
high-throughput research and point-of-care use in patients with chronic lung
disease. Image processing modules and algorithm pipelines were embedded within a
graphical user interface (based on the .NET framework) for pulmonary magnetic
resonance imaging (MRI) and x-ray computed-tomography (CT) datasets. The software
pipelines were generated using C++ and included: (1) inhaled He3/Xe129 MRI
ventilation and apparent diffusion coefficients, (2) CT-MRI coregistration for
lobar and segmental ventilation and perfusion measurements, (3) ultrashort echo
time H1 MRI proton density measurements, (4) free-breathing Fourier-decomposition
H1 MRI ventilation/perfusion and free-breathing H1 MRI specific ventilation, (5)
multivolume CT and MRI parametric response maps, and (6) MRI and CT texture
analysis and radiomics. The image analysis framework was implemented on a desktop
workstation/tablet to generate biomarkers of regional lung structure and function
related to ventilation, perfusion, lung tissue texture, and integrity as well as
multiparametric measures of gas trapping and airspace enlargement. All biomarkers
were generated within 10 min with measurement reproducibility consistent with
clinical and research requirements. The resultant pulmonary imaging biomarker
pipeline provides real-time and automated lung imaging measurements for point-of
care and high-throughput research.
PMID- 29963581
TI - Short and Long-Term Effects of Compromised Birth Weight, Head Circumference, and
Apgar Scores on Neuropsychological Development.
AB - Background: Low birth weight (LBW, <2500 g) is an adverse perinatal risk that may
reflect a poor intrauterine environment. While LBW has been a well-known
predictor of physical, neurological, cognitive and psychological deficits later
in life, minimal research has been done on small head circumference and low 5
minute Apgar scores, and their association with subsequent developmental
abnormalities. Objective: The current study aims to demonstrate that small head
circumference and low 5-minute Apgar scores are predictors for developmental
abnormalities throughout childhood and later. Methods: Using a longitudinal
design, 2,151 individuals' physical, neurological, and cognitive functioning in
childhood, as well as psychological functioning in adulthood, was assessed as a
function of three perinatal risk factors: LBW, small head circumference and low
Apgar scores. Results: Similar to findings with LBW, small head circumference or
a low Apgar score were associated with increased number of hospital visits
(p<0.0001 and p=0.005 respectively) and neurological abnormalities (p<0.0001 and
p=0.001 respectively) at age 1. Intelligence quotient (IQ) scores at ages 4 and 7
were significantly lower for those born with small head circumference (p<0.0001)
or low Apgar scores (p=0.002). Finally, the incidence of anxiety in adulthood was
significantly higher for those born with small head circumference (p=0.03) or low
Apgar scores (p=0.004) compared to their counterpart. Conclusion: Small head
circumference and low a Apgar score are predictors of later physical,
neurological, cognitive and psychological abnormalities, and can complement LBW,
a more frequently used perinatal risk factor, and thus be used to screen for
future developmental deficits, together with LBW.
PMID- 29963582
TI - Trion-Polariton Formation in Single-Walled Carbon Nanotube Microcavities.
AB - We demonstrate the formation and tuning of charged trion-polaritons in polymer
sorted (6,5) single-walled carbon nanotubes in a planar metal-clad microcavity at
room temperature. The positively charged trion-polaritons were induced by
electrochemical doping and characterized by angle-resolved reflectance and
photoluminescence spectroscopy. The doping level of the nanotubes within the
microcavity was controlled by the applied bias and thus enabled tuning from
mainly excitonic to a mixture of exciton and trion transitions. Mode splitting of
more than 70 meV around the trion energy and emission from the new lower
polariton branch corroborate a transition from exciton-polaritons (neutral) to
trion-polaritons (charged). The estimated charge-to-mass ratio of these trion
polaritons is 200 times higher than that of electrons or holes in carbon
nanotubes, which has exciting implications for the realization of polaritonic
charge transport.
PMID- 29963583
TI - High Internal Emission Efficiency of Silicon Nanoparticles Emitting in the
Visible Range.
AB - Light-emitting silicon nanoparticles (Si-NPs) are interesting for lighting
applications due to their nontoxicity, chemical robustness, and photostability;
however, they are not practically considered due to their low emission
efficiencies. While large Si-NPs emitting in the red to infrared spectral region
show ensemble emission quantum efficiencies up to 60%, the emission efficiencies
of smaller Si-NPs, emitting in the visible spectral range, are far lower,
typically below 10-20%. In this work, we test this efficiency limit by measuring
for the first time the internal quantum efficiency (IQE), i.e., the higher bound
of the emission quantum efficiency, considering only the emissive NPs within the
ensemble, of Si-NPs emitting in the visible spectral range between 350 and 650
nm. On the basis of photoluminescence decay measurements in a Drexhage geometry,
we show that Si-NPs with organic passivation (C:Si-NPs) can have high direct
bandgap-like radiative rates, which enable a high IQE over ~50%. In this way, we
demonstrate that Si-NPs can in principle be considered a competitive candidate as
a phosphor in lighting applications and medical imaging also in the visible
spectral range. Moreover, our findings show that the reason for the much lower
ensemble emission efficiency is due to the fact that the ensemble consists of a
low fraction of emissive NPs, most likely due to a low PL "blinking" duty cycle.
PMID- 29963584
TI - Generation of Luciferase-expressing Tumor Cell Lines.
AB - Murine tumor models have been critical to advances in our knowledge of tumor
physiology and for the development of effective tumor therapies. Essential to
these studies is the ability to both track tumor development and quantify tumor
burden in vivo. For this purpose, the introduction of genes that confer tumors
with bioluminescent properties has been a critical advance for oncologic studies
in rodents. Methods of introducing bioluminescent genes, such as firefly
luciferase, by viral transduction has allowed for the production of tumor cell
lines that can be followed in vivo longitudinally over long periods of time. Here
we describe methods for the production of stable luciferase expressing tumor cell
lines by lentiviral transduction.
PMID- 29963585
TI - Editorial Special Issue: Pain Management.
PMID- 29963586
TI - Assessment and Management of Cancer Pain in Older Adults: Strategies for Success.
AB - Pain is a significant problem in older adults with cancer as older adults often
receive suboptimal pain management. While overmedication can lead to adverse
effects, under management of pain can lead to physiological and psychological
problems such as functional decline and depression. This manuscript will discuss
the assessment and management of pain in older adults, in consideration of the
pharmacodynamic changes related to aging and other individual considerations.
Current evidence from filtered and unfiltered sources, PubMed, current
guidelines. Unrelieved pain can have a detrimental impact on older adults. A team
approach is essential to assess patients at each encounter, consider the social
environment in which the patient resides, and employ pharmacologic and
nonpharmacologic strategies that are evidence-based and are tailored to the
specific cancer pain syndrome.
PMID- 29963587
TI - A Concept Analysis of Self-Management of Cancer Pain.
AB - The objective of the study was to conduct a concept analysis of "self-management
of cancer pain" to develop a theoretical definition of the concept and identify
its attributes, antecedents, and outcomes. The Rodgers' evolutionary model of
concept analysis was used. Literature published from January 2000 to February
2017 containing the terms, "cancer pain" and "self-management" in their title
and/or abstract was assessed. Twenty-seven studies were selected for this
analysis. Self-management of cancer pain is defined as "the process in which
patients with cancer pain make the decision to manage their pain, enhance their
self-efficacy by solving problems caused by pain, and incorporate pain-relieving
strategies into daily life, through interactions with health-care professionals."
The attributes of self-management of cancer pain were classified into the
following five categories: Interaction with health-care professionals, decision
making to pain management, process for solving pain-related problems, self
efficacy, and incorporating strategies for pain relief into daily life. The
antecedents were classified into the following seven categories: Physical
functions, cognitive abilities, motivation, undergoing treatment for pain,
receiving individual education, receiving family and health-care professionals'
support, and health literacy. The outcomes were classified into the following
three categories: pain relief, well-being, and empowerment. The attributes of
self-management of cancer pain can be used as components of nursing practice to
promote patient self-management of cancer pain. The categories of antecedents can
be used as indicators for nursing assessment, and the outcomes can be used as
indicators for evaluations of nursing intervention.
PMID- 29963588
TI - Pain and Menopause Symptoms of Breast Cancer Patients with Adjuvant Hormonal
Therapy in Korea: Secondary Analysis.
AB - Objective: The purpose of this study was to describe the prevalence and levels of
pain and menopause symptoms of breast cancer patients with adjuvant hormonal
therapy (HT). Methods: A cross-sectional survey design was used. Secondary
analysis was used from the primary data collected in 2013 from a total of 110
breast cancer patients receiving HT for more than 3 months, using questionnaires
of the Korean version of brief pain inventory and the menopause rating scale.
Results: Mean age of the participants was 53.56. Most (88.2%) of the participants
reported to have pain and almost (95.5%) of them reported to have menopause
symptoms. More pain was reported in participants with aromatase inhibitor (AI)
than those with tamoxifen. Adherence to HT showed a significant difference
according to the rate of feeling increased pain (P = 0.001). Among the menopause
symptoms, fatigue was the most common symptom (97.3%). Sweating/flush was
significantly higher in tamoxifen group (P < 0.005), and joint and muscle
complaints were higher in AI group (P < 005). Conclusions: The results of the
study show that the prevalence and levels of pain and menopause symptoms among
breast cancer patients receiving HT were high. Thus, oncology professionals need
to provide appropriate interventions to relieve pain and menopause symptom to
improve adherence to HT.
PMID- 29963589
TI - Best Practice for the Administration of Daratumumab in Multiple Myeloma:
Australian Myeloma Nurse Expert Opinion.
AB - Patients with multiple myeloma (MM) are typically of an advanced age and may have
significant co-existing medical conditions. They have often had multiple lines of
therapy and as such experience disease-related effects alongside associated
treatment toxicities. Daratumumab is a monoclonal antibody approved for the
treatment of MM in the relapsed/refractory setting. Clinical studies found that
daratumumab showed good tolerability as a monotherapy and in combination with
current standard therapies. However, the administration of daratumumab does
require specific management considerations. It is administered as an intravenous
infusion and infusion-related reactions (IRRs) may occur. Daratumumab also
interferes with routine blood transfusion tests, giving false positives for the
indirect antiglobulin test. This article highlights key nursing care
considerations and practical management aspects to improve the treatment
experience of patients receiving daratumumab infusions. Pretreatment aspects,
patient education, pre- and post-medication, daratumumab administration, and the
management of IRRs are discussed. An IRR management sheet that could be used by
nurses and a patient information sheet are located at the end of this article.
PMID- 29963591
TI - A Nurse's Journey with Cancer.
PMID- 29963590
TI - Kant in Present Oncology Nursing Realities.
AB - Nursing as a discipline has consistently borrowed ideas from science and
philosophy to establish reality and truth. To improve the care of patients with
cancer, oncology nursing science must focus on areas of study that address
relevant cancer care issues and have a major impact on people with cancer. This
article attempted to explore the philosophical views of Immanuel Kant in relation
to the present oncology nursing realities. The connections of the views of this
philosopher as applied to modern cancer care were explored. The researchers
attempted to identify certain components in these philosophies that best suit the
present nursing realities in cancer care, especially regarding ethical and moral
practices. From the analysis, Kant identified strategic issues that are directed
toward strengthening the oncology nurse's commitments to the patients with
cancer.
PMID- 29963593
TI - Falls and Physical Inactivity in Patients with Gastrointestinal Cancer and Hand
Foot Syndrome.
AB - Objective: This study aims to ascertain the incidence and association of falls
and physical inactivity in patients with gastrointestinal cancer and hand-foot
syndrome (HFS) after receiving chemotherapy or targeted therapy. Methods: The
present cross-sectional study was conducted on 50 outpatients with HFS of Grade 1
or above, according to the National Cancer Institute Common Terminology Criteria
for Adverse Events, following the receipt of chemotherapy or targeted therapy for
gastrointestinal cancer in Japan between November 2016 and February 2017. For
measurement, Dermatology Life Quality Index (DLQI) and the International Physical
Activity Questionnaire were used. Data were analyzed by logistic regression
analysis. Results: Of the participants, 18% experienced falls and 60% reported
physical inactivity. Multivariate logistic regression revealed that the DLQI
treatment domain score was the only factor associated with falls (odds ratio [OR]
=8.01, 95% confidence interval [CI] =1.27-50.63, P = 0.027). Physical inactivity
was associated with DLQI symptom and feeling domain scores (OR = 5.54, 95% CI =
1.26-24.33, P = 0.023) and the with-oxaliplatin or paclitaxel regimen (OR = 3.71,
95% CI = 1.06-13.03, P = 0.041). Conclusions: The results of the present study
suggest patients should be informed that HFS is a risk factor for physical
inactivity and falls.
PMID- 29963594
TI - Hopelessness, Perceived Social Support and their Relationship in Iranian Patients
with Cancer.
AB - Objective: Cancer is considered a global health problem and its prevalence has
been growing in recent years. The present study was conducted to investigate the
role of hopelessness and perceived social support for Iranian patients with
cancer. Methods: Convenience sampling was used to select the study sample
comprising 100 patients with cancer presenting to the Education and Treatment
Center of Valiasr in Zanjan, Iran. A demographic questionnaire, the Beck
Hopelessness Scale, and the Social Support from Family and Friends Scale were
used to collect the data. Collected data were analyzed using SPSS-16. Results: Of
the 98 study patients, 52 (53.1%) were female and the remainder were male. Lung
cancer constituted the most prevalent type of cancer (25.5%). The mean
hopelessness score was 5.93 +/- 4.71. The mean scores for social support provided
by family and friends were 10.89 +/- 5.61 and 14.94 +/- 4.16, respectively.
Significantly negative correlations were observed between the mean scores of
hopelessness and social support provided by family (P = 0.007; r = -0.270) and
friends (P = 0.001; r = -0.327). Conclusion: According to the findings of the
present study, Iranian patients with cancer have relatively mild levels of
hopelessness and moderate levels of social support. Perceived social support was
also found to affect the patients' hopefulness. Given the lack of studies on this
subject, it is recommended that further studies are performed.
PMID- 29963592
TI - Cancer-Related Cognitive Impairment in Breast Cancer Patients: Influences of
Psychological Variables.
AB - Approximately 3.1 million women in the US are living with breast cancer and up to
75% of these women experience cancer-related cognitive impairment (CRCI). CRCI is
described as impairments in memory, verbal fluency, thought processes, and
attention span. Despite the high prevalence of breast cancer, only a few studies
have been published on CRCI and most of these studies primarily focused on its
pathophysiological mechanism. However, recent evidence has demonstrated that
breast cancer patients with CRCI are more likely to have high level of
psychologic distress, suggesting a possible relationship between CRCI and
psychologic distress. This review aims to examine existing literature that
describes CRCI in relation to psychological distress among breast cancer
patients. One thousand four hundred and ninety-eight articles were searched using
PubMed, CINAHL, and PsycINFO. Thirteen studies met inclusion criteria, and one
article was additionally pulled from article reference lists. Of these19 studies,
psychologic distress has been operationalized in varied ways such as anxiety (n =
3), depression (n = 2), both anxiety and depression (n = 4), stress (n = 4),
worry (n = 2), mental fatigue (n = 1), and undefined psychological distress (n =
2). Except for six studies designed as a longitudinal study, the rest of studies
used a cross-sectional design. Twelve studies used both subjective and objective
measures to assess cognitive function. We found that the patients with high
psychological distress displayed lower performance on cognitive function tests.
Our finding indicates that psychological variables contributed to CRCI that
breast cancer patients experienced. Areas for further investigation are proposed
that will advance the care of breast cancer patients with CRCI.
PMID- 29963595
TI - Measuring the Quality of Life among Head-and/or-Neck Cancer Patients with Oral
Mucositis Using the Functional Assessment of Cancer Therapy-General in Jordan.
AB - Objective: Quality of life (QOL) in cancer patients can be influenced by the
presence of medical conditions, such as oral mucositis (OM). There is still
limited knowledge about this issue among patients in Jordan, and this could be
related to the absence of research instruments testing QOL among cancer patients
with OM. This study measured the QOL among cancer patients using the Functional
Assessment of Cancer Therapy-General (FACT-G), Arabic version. Methods: This was
a cross-sectional study on 118 head-and/or-neck cancer patients with OM in
Jordan. Data were submitted to measures of normality, reliability, and validity
using exploratory factor analysis. The study also measured QOL among the study
sample. Results: FACT-G demonstrated good internal consistency reliability and
validity. Factor analysis indicated the presence of four factors explained by 24
items representing a valid FACT-G, Arabic version. Scores reflected low QOL
compared to reported normative values in the literature. The values used to
compare findings from this study were extracted from international literature; no
similar values were present in published literature. Conclusions: FACT-G, Arabic
version, is valid and reliable when applied to this study population. Further
testing is recommended, which would include the establishment of normative
values.
PMID- 29963596
TI - Perspectives of Oncology Unit Nurse Managers on Missed Nursing Care: A
Qualitative Study.
AB - Objective: The main objective of this study was to explore factors affecting
missed nursing care in oncology units from the perspective of nurse managers.
Methods: Twenty nurse managers working at oncology units of referral teaching
hospitals in Iran participated in this study. Data were collected through
individual face-to-face and telephonic interviews using an interview guide. Focus
groups were also conducted. Data were analyzed using conventional content
analysis. Results: System structure, underlying factors, and barriers to missed
care reports were identified as factors that affect missed nursing care.
Conclusions: Nurse managers should reduce the effects of nursing staff shortages
and increased workloads in addition to providing materials and equipment. They
need to distribute experienced staff according to the type of ward or patients'
needs. Nurse managers should create a favorable environment for reporting missed
nursing care by having an open relationship with nurses by teaching and
emphasizing nursing practice. Moreover, using a nonpunitive managerial approach
and minimizing the use of an apathetic management style can be helpful.
PMID- 29963597
TI - A Study on Cervical Cancer Screening Using Pap Smear Test and Clinical
Correlation.
AB - Objective: The objective of the study is to evaluate the use of the Pap smear
screening method for detection of precancerous lesions. Methods: All women who
visited the outpatient gynecology clinic of the Department of Obstetrics and
Gynaecology at King Georges Medical University, Lucknow, UP, India, over 1 year
for different clinical problems were recruited for the study. A total of 1650
women who were sexually active and over 21 years of age were enrolled in the
study. A clinical examination, an examination per speculum, and a vaginal
examination were performed and a history taken for all women. A Pap smear was
used for all women to screen for cervical cancer. The smear was obtained using an
Ayre spatula and spread over a marked glass slide, which was placed in 95% ethyl
alcohol and sent to the Department of Pathology for cytopathological examination.
All data were recorded using a predetermined pro forma. Women who had visible
malignant cervical lesions were excluded from the study. Results: Most women were
in the age range of 30-50 years and multiparous. Vaginal discharge was the most
common complaint, occurring in 36.96% of the women. An irregular menstrual cycle
was the complaint of 12.78% and abdominal pain of 25.63% of women, while 15.15%
were asymptomatic. The Pap smear test of 93.57% of the women was adequately
taken, while 6.42% of the individuals had an inadequate sample. The test was
negative for malignancy in 48.84%, and 42.66% had infection or inflammation.
Atypical squamous cells of undetermined significance (ASCUS), low-grade squamous
intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion
(HSIL) were detected in 2.90%, 5.09%, and 0.48%, respectively. Women with Pap
tests positive for ASCUS, LSIL, and HSIL underwent a colposcopy and guided
biopsy. Conclusions: Women with an abnormal Pap test should undergo a colposcopy,
and those with abnormal colposcopy findings should be advised to undergo a
biopsy. A Pap smear is simple, noninvasive, cost-effective, and easy to perform
for detection of precancerous lesions in a gynecological patient.
PMID- 29963598
TI - The Unmet Needs of the Family Caregivers of Patients with Cancer Visiting a
Referral Hospital in Iran.
AB - Objective: The complex process of taking care of patients with cancer can affect
various aspects of the needs and health of their family caregivers. The present
study aims to determine the unmet needs of the family caregivers of patients with
cancer and to compare it according to background variables. Methods: The present
descriptive study recruited 200 family caregivers of patients with cancer
visiting a referral hospital in Iran. Sampling was carried out through the
convenience method. Data were collected using Shin's comprehensive needs
assessment tool in seven domains (health and psychological problems,
family/social support, healthcare staff, information, religious/spiritual
support, hospital facilities/services, and practical support). Results: The mean
(+/-standard deviation) of the total scores of the unmet needs of the family
caregivers was 81.73 (+/-16.82), with a possible range of 0-123. A significant
percentage of the family caregivers of patients with cancer had unmet needs in
all of the seven domains with different severities. The mean scores were higher
in the information, healthcare staff (physicians and nurses), and health and
psychological problems domains as compared to the other domains. Conclusions: The
results showed that the majority of the family caregivers of patients with cancer
have many unmet needs, which should be addressed by professional care providers
through the development of holistic care programs targeting family caregivers by
focusing on information needs and a proper communication process.
PMID- 29963599
TI - Erratum: Education Based on Theory of Planned Behavior over Sexual Function of
Women with Breast Cancer in Iran.
AB - [This corrects the article on p. 201 in vol. 5, PMID: 29607381.].
PMID- 29963600
TI - The effect of oral dabigatran etexilate on bone density, strength, and
microstructure in healthy mice.
AB - Thrombin is a key component in the coagulation cascade where it converts factor
V, VIII, XI, and fibrinogen. In addition to the abundant production of thrombin
in the liver, osteoclasts synthesize and secrete thrombin as well. Osteoblasts
express thrombin receptors, and it has been reported that thrombin stimulates the
expression of RANKL relatively to OPG, resulting in greater osteoclast activation
and bone degradation. Pradaxa (dabigatran etexilate, DE) is a new anticoagulant,
which has recently been approved for clinical use. DE is a direct thrombin
inhibitor with potential to modulate the RANKL/OPG ratio and thereby limit
osteoclast activation and bone degradation. The purpose of the study was to
investigate whether DE can increase bone density, bone strength, and bone
microstructure in healthy male and female mice and to investigate whether the
effect of DE is sex-dependent. Twenty-eight 14-week-old male C57BL/6 mice were
stratified by weight into 4 groups: 1. Control 3 weeks; 2. DE 3 weeks; 3. Control
6 weeks; 4. DE 6 weeks. An identical study design was applied to twenty-four 14
week-old female C57BL/6 mice. Chow mixed with DE was offered ad libitum,
resulting in a dose of 1.70 mg DE/g body weight and 1.52 mg DE/g body weight, to
female and male mice, respectively. The animals were euthanized after 3 or 6
weeks. Bone mineral density (aBMD) and bone mineral content (BMC) were evaluated
with DEXA, 3D microstructural properties were determined with MUCT, bone strength
was determined with mechanical testing, and bone formation and resorption was
evaluated with bone histomorphometry. In female mice, DE resulted in significant
higher tibial aBMD values after 6 weeks of intervention. Furthermore, DE
significantly increased tibial diaphyseal cortical bone area and tissue area,
which was accompanied by significantly increased strength of the tibial shaft. DE
had no effect on femoral cortical bone or on femoral and vertebral trabecular 3D
microstructure. Finally, bone histomorphometry showed that DE had no effect on
MS/BS or Oc.S/BS. In male mice, no bone positive effects of DE were found in any
of the parameters investigated. In conclusion, intervention with DE may result in
a weak positive site specific effect at tibial cortical bone in female mice, and
importantly, no major deleterious effects of DE on bone tissue were seen in
either female or male mice despite the relatively high dose of DE used.
PMID- 29963601
TI - Vitamin D and muscle.
AB - Vitamin D is increasingly recognised to play an important role in normal muscle
function. Low vitamin D status is associated with an increased risk of falls and
proximal weakness. Since vitamin D deficiency is very common, and the signs are
non-specific, it is important to maintain a high index of suspicion of vitamin D
deficiency in patients with muscle pain and weakness, and it is simple to measure
serum 25(OH) vitamin D. Therapy is cheap, safe and effective, but sometimes a
larger dose may be needed, and, as shown in our case report, willingness of
people to pay for an over the counter medication can be an issue. Following a
striking case report that demonstrates muscle defects in severe vitamin D
deficiency, we discuss clinical studies examining specific effects of vitamin D
on physical performance, muscle strength and falls. Finally, we present an
overview of molecular mechanisms that explain vitamin D's biological effects on
muscle.
PMID- 29963602
TI - Distal radius microstructure and finite element bone strain are related to site
specific mechanical loading and areal bone mineral density in premenopausal
women.
AB - While weight-bearing and resistive exercise modestly increases aBMD, the precise
relationship between physical activity and bone microstructure, and strain in
humans is not known. Previously, we established a voluntary upper-extremity
loading model that assigns a person's target force based on their subject
specific, continuum FE-estimated radius bone strain. Here, our purpose was to
quantify the inter-individual variability in radius microstructure and FE
estimated strain explained by site-specific mechanical loading history, and to
determine whether variability in strain is captured by aBMD, a clinically
relevant measure of bone density and fracture risk. Seventy-two women aged 21-40
were included in this cross-sectional analysis. High resolution peripheral
quantitative computed tomography (HRpQCT) was used to measure macro- and micro
structure in the distal radius. Mean energy equivalent strain in the distal
radius was calculated from continuum finite element models generated from
clinical resolution CT images of the forearm. Areal BMD was used in a nonlinear
regression model to predict FE strain. Hierarchical linear regression models were
used to assess the predictive capability of intrinsic (age, height) and
modifiable (body mass, grip strength, physical activity) predictors. Fifty-one
percent of the variability in FE bone strain was explained by its relationship
with aBMD, with higher density predicting lower strains. Age and height explained
up to 31.6% of the variance in microstructural parameters. Body mass explained
9.1% and 10.0% of the variance in aBMD and bone strain, respectively, with higher
body mass indicative of greater density. Overall, results suggest that meaningful
differences in bone structure and strain can be predicted by subject
characteristics.
PMID- 29963604
TI - Occult HBV Infection in Nigeria.
AB - Occult hepatitis B virus infection (OBI) is manifested by presence of HBV-DNA in
the absence of detectable Hepatitis B surface antigen (HBsAg) with or without
anti-HBV antibodies. Hence it is a potential threat in blood transfusion
medicine. This study was carried out to determine the prevalence of OBI as well
as evaluate the effectiveness of using Hepatitis B surface antigen (HBsAg) marker
alone in the diagnosis of HBV infection among HBsAg negative blood donors in
Ilorin, Nigeria. A purposive sampling, including samples from 206 already donated
and prescreened blood units from HBsAg negative from apparently healthy volunteer
blood donors at the General Hospital Blood Transfusion Centre, Ilorin, Nigeria,
were collected for further laboratory analysis for this study. Five millilitres
of blood was collected and plasma sample tested for the presence of HBsAg using a
commercially available ELISA kit. In addition, Polymerase Chain Reaction (PCR)
was used for molecular detection of HBV DNA in each of the samples. Data was
analyzed using descriptive statistics, Chi square at p = 0.05. Of the 206 HBsAg
Micropoint(r) rapid kits pre-screened seronegative samples collected from the
blood transfusion centre, 8 (3.9%) samples were positive for the presence of
HBsAg when retested using ELISA in the laboratory. Eighteen of the 206 samples
(8.7%) were HBV-DNA positive by a semi-nested PCR technique giving an OBI rate of
8.7%. Out of the 18 HBV-DNA positive samples, 17 (4.4%) were from males and only
one (5.6%) was from a female donor. Analysis of the 18 HBV DNA positive samples
using genotype specific primers into genotype A and Non-A showed that 15 (83.3%)
were HBV genotype A, while 2 (11.1%) were genotypes other than A (Non-A), one
(5.6%) sample had mixed genotypes (A & non-A). A prevalence of 8.7% OBI found in
this study indicates substantial risk of post transfusion HBV infection in the
study area in Nigeria. Hence, the need to include HBV DNA detection in the
routine blood screening that is, using Nucleic Acid Testing (NAT) technique for
transfusion safety in the country.
PMID- 29963605
TI - Mammography to tomosynthesis: examining the differences between two-dimensional
and segmented-three-dimensional visual search.
AB - Background: Radiological techniques for breast cancer detection are undergoing a
massive technological shift-moving from mammography, a process that takes a two
dimensional (2D) image of breast tissue, to tomosynthesis, a technique that
creates a segmented-three-dimensional (3D) image. There are distinct benefits of
tomosynthesis over mammography with radiologists having fewer false positives and
more accurate detections; yet there is a significant and meaningful disadvantage
with tomosynthesis in that it takes longer to evaluate each patient. This added
time can dramatically impact workflow and have negative attentional and cognitive
impacts on interpretation of medical images. To better understand the nature of
segmented-3D visual search and the implications for radiology, the current study
looked to establish a new testing platform that could reliably examine
differences between 2D and segmented-3D search. Results: In Experiment 1, both
professionals (radiology residents and certified radiologists) and non
professionals (undergraduate students) were found to have fewer false positives
and were more accurate in segmented-3D displays, but at the cost of taking
significantly longer in search. Experiment 2 tested a second group of non
professional participants, using a background that more closely resembled a
mammogram, and replicated the results of Experiment 1-search was more accurate
and there were fewer false alarms in segmented 3D displays but took more time.
Conclusion: The results of Experiments 1 and 2 matched the performance patterns
found in previous radiology studies and in the clinic, suggesting this novel
experimental paradigm potentially provides a flexible and cost-effective tool
that can be utilized with non-professional populations to inform relevant visual
search performance. From an academic perspective, this paradigm holds promise for
examining the nature of segmented-3D visual search.
PMID- 29963603
TI - Physiologic and pathophysiologic roles of extra renal CYP27b1: Case report and
review.
AB - Although the kidney was initially thought to be the sole organ responsible for
the production of 1,25(OH)2D via the enzyme CYP27b1, it is now appreciated that
the expression of CYP27b1 in tissues other than the kidney is wide spread.
However, the kidney is the major source for circulating 1,25(OH)2D. Only in
certain granulomatous diseases such as sarcoidosis does the extra renal tissue
produce sufficient 1,25(OH)2D to contribute to the circulating levels, generally
associated with hypercalcemia, as illustrated by the case report preceding the
review. Therefore the expression of CYP27b1 outside the kidney under normal
circumstances begs the question why, and in particular whether the extra renal
production of 1,25(OH)2D has physiologic importance. In this chapter this
question will be discussed. First we discuss the sites for extra renal 1,25(OH)2D
production. This is followed by a discussion of the regulation of CYP27b1
expression and activity in extra renal tissues, pointing out that such regulation
is tissue specific and different from that of CYP27b1 in the kidney. Finally the
physiologic significance of extra renal 1,25(OH)2D3 production is examined, with
special focus on the role of CYP27b1 in regulation of cellular proliferation and
differentiation, hormone secretion, and immune function. At this point the data
do not clearly demonstrate an essential role for CYP27b1 expression in any tissue
outside the kidney, but several examples pointing in this direction are provided.
With the availability of the mouse enabling tissue specific deletion of CYP27b1,
the role of extra renal CYP27b1 expression in normal and pathologic states can
now be addressed definitively.
PMID- 29963606
TI - Perceived usability of the National Competence Based Catalogue of Learning
Objectives for Undergraduate Medical Education by medical educators at the
Hannover Medical School.
AB - Background: The aim of this study was to assess usability and identify possible
challenges in the implementation of the National Competence Based Catalogue of
Learning Objectives for Undergraduate Medical Education (NKLM) among medical
educators. Methods: A comprehensive survey among experienced medical educators
(responsible for the teaching content and didactical development in their
module/field) based on the System Usability Scale (SUS) was carried out focusing
on the awareness, usability and challenges of the NKLM. Results: The
questionnaire was completed by 52 of the 64 addressed educators. Most of the
participants had 6-10 years of teaching experience. 30% of the educators were not
familiar with the NKLM. During the evaluation of the NKLM, usability was rather
poorly rated. However, 71.9% of medical educators agreed that the various aspects
of the medical professions were well integrated in the NKLM with only 12,5%
stating that they would not use the NKLM for teaching and lesson preparation.
Conclusion: The awareness and promotion of the NKLM need to be improved.
Furthermore, these data suggest that - although difficult to use - there is a
solid acceptance of the content of the NKLM. Medical educators seem to be willing
to use the NKLM. Therefore, further attempts to support colleagues with the
handling of the NKLM seem to be inevitable to pave the way for a competency-based
curricular change.
PMID- 29963607
TI - Ward rounds in internal medicine: Validation of an Entrustable Professional
Activity (EPA) observation checklist.
AB - Objectives: Ward rounds serve a crucial daily activity in hospitals. Building on
the Entrustable Professional Activity "Conducting internal medicine ward rounds"
consisting of ten competencies and 25 corresponding activities, this study aims
at assessing content and external validity of an observation checklist for this
EPA. Methods: A focus group aimed at content validation of the checklist. Five
participants therefore evaluated it with respect to comprehensiveness and
comprehensibility. To investigate external validity, 14 authentic ward rounds
were video-taped and rated by two raters with the adapted observation checklist
in terms of the appearance of certain activities in the videos. Results: After
some adaptions, participants of the focus group agreed on a checklist consisting
of nine competencies, 25 activities and 110 examples of observable behaviours
supporting content validity. External validity was studied by using the
observation checklist for ratings of ward round videos. The checklist was
regarded as a valuable tool to structure observation. Along with the high
frequencies of observed behaviour and interrater-reliability, external validity
can be assumed. Conclusion: The first scientifically developed comprehensive
observation checklist for the EPA conducting a ward round in internal medicine is
presented. The checklist is a valuable tool for providing elaborated feedback in
undergraduate and graduate medical education. Focussing on multi-institutional
validation and the cut offs of the checklist to determine the levels of
entrustment are recommended for future research.
PMID- 29963609
TI - Research into finding a stable prognosis parameter for the detection of students
in need of guidance - Realization of equal opportunities through a diversity
oriented study guidance.
AB - Objective: The internationalization of teaching and studying as well as
increasing numbers of students with increasingly heterogeneous educational
biographies and lifestyles require universities to develop awareness of this
diversity and the need for adequate diversity management. For some diversity
criteria at least it has been proven that they can influence the individual study
success of students. The Dean's Office of the Medical Faculty of the University
of Cologne has empirically determined a stable prognosis parameter for study
progression on the basis of selected criteria in order to enable early detection
of students in need of guidance. This will then be used for targeted, diversity
oriented study guidance. On the one hand a correspondingly adapted guidance offer
should take into account individual study progressions. On the other hand,
measures to improve the equal opportunities of students with regard to their
academic success can be discussed. Methodology: With the help of study
progression analyses, study progress of cohorts can be recorded longitudinally.
The study progression analysis implemented in the control of faculty teaching
serves as a central forecasting and steering tool for the forthcoming concept of
diversity-oriented study guidance. The significance measurement of the various
features is determined using binary logistic regression analyses. Results: As
part of the study progression analyses, the study success rate after the first
semester has the strongest influence on the concordance with the minimum duration
of study in the pre-clinical phase, followed by the characteristics age at
commencement of studies and place of university entrance qualification. The
school leaving grade only just misses the required significance level of p <0.05.
As a predictor gender provides no explanatory contribution in the considered
model. Conclusion: In order to do justice to the heterogeneity among the
students, university administrators and lecturers should understand the
recognition of diversity as a cross-cutting task and keep an eye on diversity
related aspects and discrimination-critical topics for different target groups as
well as individual guidance services in the context of individual study guidance.
Within the scope of this study, we were able to empirically prove the stable
prognosis parameter study success rate after the first semester allows reliable
detection of students in need of guidance. The explanatory contribution is larger
than any of the individual criteria examined in this study. The specific causes
that led to a delay in studying will be analyzed in the context of downstream and
diversity-oriented study guidance. A follow-up study will deal with the question
of whether the success of students requiring study guidance can be significantly
improved by subsequent study guidance.
PMID- 29963610
TI - Investigation on the acquisition of scientific competences during medical studies
and the medical doctoral thesis.
AB - Background: Not only the amount of research related contents in German medical
studies are objects of criticism, but also the medical doctoral thesis. However,
the question which research competences are truly acquired within medical school
and the doctoral phase is empirically open, and is thus pursued in the following
research study. Methods: We used data from the Bavarian Medical Graduate Panel
Survey (MediBAP) (N=455), where respondents assessed their own research
competences. To consolidate the data, we analysed qualitative interviews with
doctoral medical graduates and students from the E-Prom study (N=14). Results:
The quantitative analyses show that medical graduates evaluate the medical
curriculum's research contents and their acquired competences as rather low.
Doctoral graduates rate their competence of pursuing research independently
higher than medical graduates who have not finished their doctorate. The
qualitative analyses are in line with these results, as they point to the
predominant development of competences during the doctoral phase. Despite this
clearly positive trend, the majority of the respondents don't feel confident
enough to undertake research independently also after attaining their doctoral
degree. Conclusion: The results of this study emphasize the need for a more
systematic and targeted mediation and review of research competences within the
regular medical curriculum.
PMID- 29963608
TI - Does teaching social and communicative competences influence dental students'
attitudes towards learning communication skills? A comparison between two dental
schools in Germany.
AB - Introduction: Teaching social and communicative competences has become an
important part of undergraduate dental education. The aim of this study was to
explore the influence of a longitudinal curriculum, addressing social and
communication skills, on dental students' attitudes towards learning these
skills. Material and methods: Data on the attitudes towards learning
communication skills were collected at two German universities and compared in a
cross-sectional survey. 397 dental students were included, 175 students attended
a longitudinal curriculum addressing social and communicative competences while
222 students did not. The dental students' attitude towards learning
communication skills was measured by a German version of the Communication Skills
Attitude Scale (CSAS-D). Results: Dental students who participated in a
longitudinal communication curriculum had significantly lower negative attitudes
towards learning communication skills than students who did not attend such
courses. Differences in positive attitudes could not be found. Significant
interaction effects were found for the factors gender and section of study:
female students in the clinical section of their study who participated in the
longitudinal curriculum reported higher positive attitudes and lower negative
attitudes compared to female students in the preclinical section of study.
Conclusion: The results of this study indicate that a longitudinal curriculum
addressing communication skills can enhance positive and reduce negative
attitudes towards learning communication skills. More longitudinal data is needed
to explore to what extent gender affects development of communication skills and
how students' attitudes towards learning communication change in the long run.
PMID- 29963611
TI - Medical Education for "Generation Z": Everything online?! - An analysis of
Internet-based media use by teachers in medicine.
AB - Aim: The aims of this study were to gain an overview of the web-based media used
during the clinical phase of medical study at German medical schools and to
identify the resources needed for web-based media use. Also examined were the
influences on web-based media use, for instance, the assessment of their
suitability for use in teaching. Method: An online survey of 264 teacher
coordinators in internal medicine, surgery, anesthesiology, gynecology,
pediatrics and psychiatry was conducted in March and April, 2016. This survey was
carried out in the German-speaking countries using a 181-item questionnaire
developed by us. Analysis took place in the form of descriptive and exploratory
data analysis. Results: The response rate was 34.8% with 92 responses. Individual
web-based media were actively used in the classroom by a maximum of 28% of
participants. Reasons cited against using web-based media in teaching included
the amount of time required and lack of support staff. The assessment of
suitability revealed that interactive patient cases, podcasts and subject
specific apps for teaching medicine were predominantly viewed as constructive
teaching tools. Social media such as Facebook and Twitter were considered
unsuitable. When using web-based media and assessing their suitability for
teaching, no correlations with the personal profiles of the teachers were found
in the exploratory analysis, except regarding the use of different sources of
information. Conclusion: Despite the Internet's rapid development in the past 15
years, web-based media continue to play only a minor role in teaching medicine.
Above all, teacher motivation and sufficient staff resources are necessary for
more effective use of Internet-based media in the future.
PMID- 29963612
TI - The impact of the program structure at Hannover Medical School on academic
success in medical studies.
AB - Aim: The classical course structure for medicine in Germany is separated by three
sections of the medical state examination. This structure is generally regarded
as sensible and unchangeable. Because the special program structure at Hannover
Medical School (MHH) has one integrated, rather than two separate study blocks,
it is possible to examine the influence of structural modifications on the study
success of different admission groups. Methods: The data was obtained from
students admitted to the MHH between 2006 and 2008 in different admission quotas.
Study success was defined as the successful completion of the entire program, but
completion of the first section of the state examination was also analysed.
Results: More students from the best "Abitur" (school leaving examinations) quota
successfully completed their studies than those accepted via the selection
process of the universities. The latter were more successful than students from
the waiting list quota. However the successful graduates of this last group
completed their studies more often within the prescribed period of study,
although they needed more time for completing all parts of the first section of
the state examination. Conclusion: The data shows that an integrated course
structure can offer, in particular, students from the waiting list quota, the
opportunity to compensate for delays in the first years of study. However, they
do not provide any evidence which applicants are best suited to meet the social
and professional requirements of trained doctors. Due to the complex structure of
such longitudinal studies, our results allow more than one plausible
interpretation.
PMID- 29963613
TI - Does it matter who writes down the feedback? A comparison of teacher- vs. student
completed clinical encounter cards during clinical rotations in veterinary
studies.
AB - Objective: Despite the fact that feedback (FB) provided by teachers to students
is a recognised, effective teaching tool, successful use of feedback during
clinical training depends on many factors. In addition to appropriate training
and attitude of teachers, sustainable feedback requires an appropriate teaching
culture and active commitment on the part of the students to receive, accept and
use FB. This study examines the use of two different clinical encounter cards
(CECs) during clinical rotation and investigates whether students take a more
active part in the feedback process when using these cards. The objective of this
study is to test whether it has a positive effect if students write down FB
themselves and to verify this positive effect. Methodology: 161 students in their
9th semester of veterinary studies each had to use two clinical encounter cards
(types 1 and 2) during their rotations on 10 wards. For this, students had to ask
teachers for FB before starting a clinical activity. The oral FB given by the
teachers was either written down on the CEC by the teachers (CEC type 1) or by
the students (CEC type 2). Furthermore, the students were asked to assess their
own performance by means of anchor criteria and to evaluate the quality of the FB
provided by the teachers. Based on the entries in the CECs submitted, the
following indicators for both CEC types could be calculated: (1) FB quantity and
quality (length and specificity), (2) differentiation of self-assessment, as well
as (3) level of satisfaction with the FB provided by the teachers. Results: With
2,377 CECs submitted, the mean CEC return rate was 74%. 99% of the cards showed
positive FB, 69% contained constructive FB with suggestions for improvement, and
87% suggested specific next steps. On average, the FB written down by teachers
was longer (12.4 versus 9.7 words) and more specific (1.9 versus 1.7 out of 3)
than FB written down by students. Length and specificity decreased in the course
of the semester. Neither the differentiation of self-assessment (proportion of
differentiated entering of self-assessment) nor the students' level of
satisfaction with the FB differed between the two examined CEC variants.
Conclusion: The use of CECs across the cohort was successfully possible; however,
the fact that students formulated and wrote down the FB themselves did not result
in more comprehensive or more specific FB. Self-assessment and level of
satisfaction with the teachers' FB remained unchanged.
PMID- 29963615
TI - Illustrated versus non-illustrated anatomical test items in anatomy course tests
and German Medical Licensing examinations (M1).
AB - Illustrated Multiple-choice questions (iMCQs) form an integral part of written
tests in anatomy. In iMCQs, the written question refers to various types of
figures, e. g. X-ray images, micrographs of histological sections, or drawings of
anatomical structures. Since the inclusion of images in MCQs might affect item
performance we compared characteristics of anatomical items tested with iMCQs and
non-iMCQs in seven tests of anatomy courses and in two written parts of the first
section of the German Medical Licensing Examination (M1). In summary, we compared
25 iMCQs and 163 non-iMCQs from anatomy courses, and 27 iMCQs and 130 non-iMCQs
from the written part of the M1 using a nonparametric test for unpaired samples.
As a result, there were no significant differences in difficulty and
discrimination levels between iMCQs and non-iMCQs, the same applied to an
analysis stratified for MCQ formats. We conclude that the illustrated item format
by itself does not seem to affect item difficulty. The present results are
consistent with previous retrospective studies which showed no significant
differences of test or item characteristics between iMCQs and non-iMCQs.
PMID- 29963616
TI - The Gesellschaft fur Medizinische Ausbildung (GMA) celebrates 40 Years of
Education Research.
PMID- 29963614
TI - Critical appraisal of RCTs by 3rd year undergraduates after short courses in EBM
compared to expert appraisal.
AB - Introduction: An essential aim of courses in evidence-based medicine (EBM) is to
improve the skills for reading and interpreting medical literature adequately.
Regarding the conceptual framework, it is important to consider different
educational levels. Aim: Our primary aim was to investigate the applicability of
different instruments for the assessment of methodological study quality by 3rd
grade students after short courses in EBM. Our secondary outcomes were agreement
with expert assessments and student's knowledge and competences. Methods: We
conducted four short courses in EBM of 90 minutes each for health care management
and medical students focused on critical appraisal of the literature. At the end,
the students assessed five publications about randomized controlled trials (RCTs)
using five different instruments; the results were compared to expert
assessments. Results: In total, 167 students participated in our EBM courses.
Students' assessments showed a non-systematic over- and underestimation of risk
of bias compared to expert assessments with no clear direction. Agreement with
expert assessments ranged between 66% to over 80%. Across RCTs, evidence was
found that the choice of instrument had an impact on agreement rates between
expert and student assessments (p=0.0158). Three RCTs showed an influence of the
instrument on the agreement rate (p<0.05 each). Discussion: Our results contrast
sharply with those of many other comparable evaluations. Reasons may be a lack of
students' motivation due to the compulsory courses, and the comparison to a
reference standard in addition to self-ratings causing objectivity. Conclusion:
Undergraduates should become familiar with the principles of EBM, including
research methods, and the reading of scientific papers as soon as possible. For a
deeper understanding, clinical experience seems to be an indispensable
precondition. Based on our results, we would recommend an integration of lectures
about EBM and critical appraisal at least twice during studies and with greater
intensity shortly before graduation.
PMID- 29963617
TI - Early Abrogation of Gelatinase Activity Extends the Time Window for tPA
Thrombolysis after Embolic Focal Cerebral Ischemia in Mice.
AB - Acute ischemic stroke (AIS) is caused by clotting in the cerebral arteries,
leading to brain oxygen deprivation and cerebral infarction. Recombinant human
tissue plasminogen activator (tPA) is currently the only Food and Drug
Administration-approved drug for ischemic stroke. However, tPA has to be
administered within 4.5 h from the disease onset and delayed treatment of tPA can
increase the risk of neurovascular impairment, including neuronal cell death,
blood-brain barrier (BBB) disruption, and hemorrhagic transformation. A key
contributing factor for tPA-induced neurovascular impairment is activation of
matrix metalloproteinase-9 (MMP-9). We used a clinically-relevant mouse embolic
model of focal-cerebral ischemia by insertion of a single embolus of blood clot
to block the right middle cerebral artery. We showed that administration of the
potent and highly selective gelatinase inhibitor SB-3CT extends the time window
for administration of tPA, attenuating infarct volume, mitigating BBB disruption,
and antagonizing the increase in cerebral hemorrhage induced by tPA treatment. We
demonstrated that SB-3CT attenuates tPA-induced expression of vascular MMP-9,
prevents gelatinase-mediated cleavage of extracellular laminin, rescues
endothelial cells, and reduces caveolae-mediated transcytosis of endothelial
cells. These results suggest that abrogation of MMP-9 activity mitigates the
detrimental effects of tPA treatment, thus the combination treatment holds great
promise for extending the therapeutic window for tPA thrombolysis, which opens
the opportunity for clinical recourse to a greater number of patients.
PMID- 29963618
TI - Simultaneous Ablation of Neuronal Neurofascin and Ankyrin G in Young and Adult
Mice Reveals Age-Dependent Increase in Nodal Stability in Myelinated Axons and
Differential Effects on the Lifespan.
AB - Nodes of Ranvier are unique regions where voltage-gated sodium channels are
highly enriched to drive saltatory conduction. Genetic ablations in adult mice
with loss of specific nodal proteins causes slow but progressive nodal
deterioration associated with decreased nerve conduction and axonopathy. What has
remained unaddressed is whether loss of nodal proteins at different time points
in postnatal life follows similar timelines of nodal disorganization. Here we
utilized simultaneous ablation of Neurofascin (NF186) and Ankyrin G (AnkG) in
mice of both sexes at three specific time points. We report that concurrent
ablation of these core nodal components at postnatal day 13 (P13) leads to
accelerated nodal destabilization in comparison with P23, and this
disorganization is even slower when ablated at P93. Ablation of NF186 with AnkG
at P13 reduced the half-life of NF186 to 15 days compared to 1 month at P23,
which increased to 2 months at P93, indicating increasing nodal stability. The
half-life of AnkG at the nodes also increased with age but showed enhanced
disappearance from the node in the absence of NF186, with a half-life of 3 days
at P13 ablation. The nodal disorganization occurred in a sequential manner, with
AnkG disappearing first from the nodal areas irrespective of the timing of
ablation, and led to decreased nerve conduction and affected axonal health.
Together, our studies reveal that nodes of Ranvier in myelinated axons continue
to become more stable with age and suggest that nodal disorganization in adult
human demyelinating disorders occurs slowly until neurological symptoms become
evident.
PMID- 29963619
TI - Orangutans venture out of the rainforest and into the Anthropocene.
AB - Conservation benefits from understanding how adaptability and threat interact to
determine a taxon's vulnerability. Recognizing how interactions with humans have
shaped taxa such as the critically endangered orangutan (Pongo spp.) offers
insights into this relationship. Orangutans are viewed as icons of wild nature,
and most efforts to prevent their extinction have focused on protecting minimally
disturbed habitat, with limited success. We synthesize fossil, archeological,
genetic, and behavioral evidence to demonstrate that at least 70,000 years of
human influence have shaped orangutan distribution, abundance, and ecology and
will likely continue to do so in the future. Our findings indicate that
orangutans are vulnerable to hunting but appear flexible in response to some
other human activities. This highlights the need for a multifaceted, landscape
level approach to orangutan conservation that leverages sound policy and
cooperation among government, private sector, and community stakeholders to
prevent hunting, mitigate human-orangutan conflict, and preserve and reconnect
remaining natural forests. Broad cooperation can be encouraged through incentives
and strategies that focus on the common interests and concerns of different
stakeholders. Orangutans provide an illustrative example of how acknowledging the
long and pervasive influence of humans can improve strategies to preserve
biodiversity in the Anthropocene.
PMID- 29963620
TI - Podocyte injury elicits loss and recovery of cellular forces.
AB - In the healthy kidney, specialized cells called podocytes form a sophisticated
blood filtration apparatus that allows excretion of wastes and excess fluid from
the blood while preventing loss of proteins such as albumin. To operate
effectively, this filter is under substantial hydrostatic mechanical pressure.
Given their function, it is expected that the ability to apply mechanical force
is crucial to the survival of podocytes. However, to date, podocyte
mechanobiology remains poorly understood, largely because of a lack of
experimental data on the forces involved. We perform quantitative, continuous,
nondisruptive, and high-resolution measurements of the forces exerted by
differentiated podocytes in real time using a recently introduced functional
imaging modality for continuous force mapping. Using an accepted model for
podocyte injury, we find that injured podocytes experience near-complete loss of
cellular force transmission but that this loss of force is reversible under
certain conditions. The observed changes in force correlate with F-actin
rearrangement and reduced expression of podocyte-specific proteins. By
introducing robust and high-throughput mechanical phenotyping and by
demonstrating the significance of mechanical forces in podocyte injury, this
research paves the way to a new level of understanding of the kidney. In
addition, in an advance over established force mapping techniques, we integrate
cellular force measurements with immunofluorescence and perform continuous long
term force measurements of a cell population. Hence, our approach has general
applicability to a wide range of biomedical questions involving mechanical
forces.
PMID- 29963622
TI - Mandatory labels can improve attitudes toward genetically engineered food.
AB - The prospect of state and federal laws mandating labeling of genetically
engineered (GE) food has prompted vigorous debate about the consequences of the
policy on consumer attitudes toward these technologies. There has been
substantial debate over whether mandated labels might increase or decrease
consumer aversion toward genetic engineering. This research aims to help resolve
this issue using a data set containing more than 7800 observations that measures
levels of opposition in a national control group compared to levels in Vermont,
the only U.S. state to have implemented mandatory labeling of GE foods.
Difference-in-difference estimates of opposition to GE food before and after
mandatory labeling show that the labeling policy led to a 19% reduction in
opposition to GE food. The findings help provide insights into the psychology of
consumers' risk perceptions that can be used in communicating the benefits and
risks of genetic engineering technology to the public.
PMID- 29963621
TI - City-level climate change mitigation in China.
AB - As national efforts to reduce CO2 emissions intensify, policy-makers need
increasingly specific, subnational information about the sources of CO2 and the
potential reductions and economic implications of different possible policies.
This is particularly true in China, a large and economically diverse country that
has rapidly industrialized and urbanized and that has pledged under the Paris
Agreement that its emissions will peak by 2030. We present new, city-level
estimates of CO2 emissions for 182 Chinese cities, decomposed into 17 different
fossil fuels, 46 socioeconomic sectors, and 7 industrial processes. We find that
more affluent cities have systematically lower emissions per unit of gross
domestic product (GDP), supported by imports from less affluent, industrial
cities located nearby. In turn, clusters of industrial cities are supported by
nearby centers of coal or oil extraction. Whereas policies directly targeting
manufacturing and electric power infrastructure would drastically undermine the
GDP of industrial cities, consumption-based policies might allow emission
reductions to be subsidized by those with greater ability to pay. In particular,
sector-based analysis of each city suggests that technological improvements could
be a practical and effective means of reducing emissions while maintaining growth
and the current economic structure and energy system. We explore city-level
emission reductions under three scenarios of technological progress to show that
substantial reductions (up to 31%) are possible by updating a disproportionately
small fraction of existing infrastructure.
PMID- 29963624
TI - Seismically determined elastic parameters for Earth's outer core.
AB - Turbulent convection of the liquid iron alloy outer core generates Earth's
magnetic field and supplies heat to the mantle. The exact composition of the iron
alloy is fundamentally linked to the processes powering the convection and can be
constrained by its seismic properties. Discrepancies between seismic models
determined using body waves and normal modes show that these properties are not
yet fully agreed upon. In addition, technical challenges in experimentally
measuring the equation-of-state (EoS) parameters of liquid iron alloys at high
pressures and temperatures further complicate compositional inferences. We
directly infer EoS parameters describing Earth's outer core from normal mode
center frequency observations and present the resulting Elastic Parameters of the
Outer Core (EPOC) seismic model. Unlike alternative seismic models, ours requires
only three parameters and guarantees physically realistic behavior with
increasing pressure for a well-mixed homogeneous material along an isentrope,
consistent with the outer core's condition. We show that EPOC predicts available
normal mode frequencies better than the Preliminary Reference Earth Model (PREM)
while also being more consistent with body wave-derived models, eliminating a
long-standing discrepancy. The velocity at the top of the outer core is lower,
and increases with depth more steeply, in EPOC than in PREM, while the density in
EPOC is higher than that in PREM across the outer core. The steeper profiles and
higher density imply that the outer core comprises a lighter but more
compressible alloy than that inferred for PREM. Furthermore, EPOC's steeper
velocity gradient explains differential SmKS body wave travel times better than
previous one-dimensional global models, without requiring an anomalously slow ~90
to 450-km-thick layer at the top of the outer core.
PMID- 29963625
TI - Rapid Red Sea Deep Water renewals caused by volcanic eruptions and the North
Atlantic Oscillation.
AB - The Red Sea hosts a deep marine environment unique among the world's oceans. It
is occupied, almost homogeneously from the subsurface (~137 to 300 m) to depths
over 2000 m, by a warm (~21.5 degrees C) and highly saline (~40.5) water mass,
referred to as the Red Sea Deep Water (RSDW). Previous studies suggested that the
RSDW is mainly ventilated, continuously or intermittently, by dense outflows from
the northern Gulfs of Suez and Aqaba with a resulting sluggish renewal time on
the order of 36 to 90 years. We use six repeated hydrographic observations
spanning the period 1982-2011 and simulations of an ocean general circulation
model with realistic atmospheric forcing to show that large portions of the RSDW
were episodically replaced during 1982-2001 by new dense waters mainly formed by
open-ocean deep convections in the northern Red Sea during anomalously cold
winters, pointing to a much shorter renewal time for the RSDW on the order of a
decade. We further show that the winter cooling anomaly in the Red Sea region was
a part of a large-scale climate variability pattern associated with either large
volcanic eruptions or the North Atlantic Oscillation (NAO). Consequently,
significant deep water formation events occurred in the Red Sea in the winters
following the 1982 El Chichon eruption in Mexico and the 1991 Mount Pinatubo
eruption in the Philippines and during the strong positive phase of the NAO in
the winter of 1989.
PMID- 29963623
TI - The neuronal S100B protein is a calcium-tuned suppressor of amyloid-beta
aggregation.
AB - Amyloid-beta (Abeta) aggregation and neuroinflammation are consistent features in
Alzheimer's disease (AD) and strong candidates for the initiation of
neurodegeneration. S100B is one of the most abundant proinflammatory proteins
that is chronically up-regulated in AD and is found associated with senile
plaques. This recognized biomarker for brain distress may, thus, play roles in
amyloid aggregation which remain to be determined. We report a novel role for the
neuronal S100B protein as suppressor of Abeta42 aggregation and toxicity. We
determined the structural details of the interaction between monomeric Abeta42
and S100B, which is favored by calcium binding to S100B, possibly involving
conformational switching of disordered Abeta42 into an alpha-helical conformer,
which locks aggregation. From nuclear magnetic resonance experiments, we show
that this dynamic interaction occurs at a promiscuous peptide-binding region
within the interfacial cleft of the S100B homodimer. This physical interaction is
coupled to a functional role in the inhibition of Abeta42 aggregation and
toxicity and is tuned by calcium binding to S100B. S100B delays the onset of
Abeta42 aggregation by interacting with Abeta42 monomers inhibiting primary
nucleation, and the calcium-bound state substantially affects secondary
nucleation by inhibiting fibril surface-catalyzed reactions through S100B binding
to growing Abeta42 oligomers and fibrils. S100B protects cells from Abeta42
mediated toxicity, rescuing cell viability and decreasing apoptosis induced by
Abeta42 in cell cultures. Together, our findings suggest that molecular targeting
of S100B could be translated into development of novel approaches to ameliorate
AD neurodegeneration.
PMID- 29963626
TI - Probing measurement-induced effects in quantum walks via recurrence.
AB - Measurements on a quantum particle unavoidably affect its state, since the
otherwise unitary evolution of the system is interrupted by a nonunitary
projection operation. To probe measurement-induced effects in the state dynamics
using a quantum simulator, the challenge is to implement controlled measurements
on a small subspace of the system and continue the evolution from the
complementary subspace. A powerful platform for versatile quantum evolution is
represented by photonic quantum walks because of their high control over all
relevant parameters. However, measurement-induced dynamics in such a platform
have not yet been realized. We implement controlled measurements in a discrete
time quantum walk based on time-multiplexing. This is achieved by adding a
deterministic outcoupling of the optical signal to include measurements
constrained to specific positions resulting in the projection of the walker's
state on the remaining ones. With this platform and coherent input light, we
experimentally simulate measurement-induced single-particle quantum dynamics. We
demonstrate the difference between dynamics with only a single measurement at the
final step and those including measurements during the evolution. To this aim, we
study recurrence as a figure of merit, that is, the return probability to the
walker's starting position, which is measured in the two cases. We track the
development of the return probability over 36 time steps and observe the onset of
both recurrent and transient evolution as an effect of the different measurement
schemes, a signature which only emerges for quantum systems. Our simulation of
the observed one-particle conditional quantum dynamics does not require a genuine
quantum particle but is demonstrated with coherent light.
PMID- 29963627
TI - Branching geometry of valley networks on Mars and Earth and its implications for
early Martian climate.
AB - Mars' surface bears the imprint of valley networks formed billions of years ago.
Whether these networks were formed by groundwater sapping, ice melt, or fluvial
runoff has been debated for decades. These different scenarios have profoundly
different implications for Mars' climatic history and thus for its habitability
in the distant past. Recent studies on Earth revealed that valley networks in
arid landscapes with more surface runoff branch at narrower angles, while in
humid environments with more groundwater flow, branching angles are much wider.
We find that valley networks on Mars generally tend to branch at narrow angles
similar to those found in arid landscapes on Earth. This result supports the
inference that Mars once had an active hydrologic cycle and that Mars' valley
networks were formed primarily by overland flow erosion, with groundwater seepage
playing only a minor role.
PMID- 29963628
TI - Permselectivity limits of biomimetic desalination membranes.
AB - Water scarcity and inadequate membrane selectivity have spurred interest in
biomimetic desalination membranes, in which biological or synthetic water
channels are incorporated in an amphiphilic bilayer. As low channel densities
(0.1 to 10%) are required for sufficient water permeability, the amphiphilic
bilayer matrix will play a critical role in separation performance. We determine
selectivity limits for biomimetic membranes by studying the transport behavior of
water, neutral solutes, and ions through the bilayers of lipid and block
copolymer vesicles and projecting performance for varying water channel
densities. We report that defect-free biomimetic membranes would have water/salt
permselectivities ~108-fold greater than current desalination membranes. In
contrast, the solubility-based permeability of lipid and block-copolymer bilayers
(extending Overton's rule) will result in poor rejection of hydrophobic solutes.
Defect-free biomimetic membranes thus offer great potential for seawater
desalination and ultrapure water production, but would perform poorly in
wastewater reuse. Potential strategies to limit neutral solute permeation are
discussed.
PMID- 29963629
TI - Endothelial siRNA delivery in nonhuman primates using ionizable low-molecular
weight polymeric nanoparticles.
AB - Dysfunctional endothelial cells contribute to the pathophysiology of many
diseases, including vascular disease, stroke, hypertension, atherosclerosis,
organ failure, diabetes, retinopathy, and cancer. Toward the goal of creating a
new RNA-based therapy to correct aberrant endothelial cell gene expression in
humans, efficient gene silencing in the endothelium of nonhuman primates was
achieved by delivering small interfering RNA (siRNA) with 7C1, a low-molecular
weight, ionizable polymer that forms nanoparticles. After a single intravenous
administration of 1 mg of siRNA per kilogram of animal, 7C1 nanoparticles
delivering Tie2 siRNA caused Tie2 mRNA levels to decrease by approximately 80% in
the endothelium of the lung. Significant decreases in Tie2 mRNA were also found
in the heart, retina, kidney, pancreas, and bone. Blood chemistry and liver
function analysis before and after treatment all showed protein and enzyme
concentrations within the normal reference ranges. Furthermore, after controlling
for siRNA-specific effects, no significant increases in inflammatory cytokine
concentrations were found in the serum. Similarly, no gross lesions or
significant underlying pathologies were observed after histological examination
of nonhuman primate tissues. This study is the first demonstration of endothelial
gene silencing in multiple nonhuman primate organs using systemically
administered siRNA nanoparticles and highlights the potential of this approach
for the treatment of disease in humans.
PMID- 29963630
TI - Bioactive polyamine production by a novel hybrid system comprising multiple
indigenous gut bacterial strategies.
AB - Metabolites of the intestinal microbiota are thought to be generated through
metabolic pathways spanning multiple taxa of intestinal bacteria. We have
previously shown that the level of putrescine, a polyamine found abundantly in
the human intestinal lumen, is increased in the colonic lumen following
administration of arginine and the probiotic Bifidobacterium sp.; however, the
underlying mechanism remained poorly understood. We report a novel pathway for
putrescine production from arginine through agmatine involving the collaboration
of two bacterial groups, and triggered by environmental acidification (drop in pH
to below 6.5 from neutral). This pathway comprises the acid tolerance system of
Escherichia coli, representing bacteria that have an arginine-dependent acid
resistance system; the energy production system of Enterococcus faecalis,
representing bacteria that have an agmatine deiminase system; and the acid
production system of the acid-producing bacteria, represented by Bifidobacterium
spp. This pathway is unique in that it represents a relationship between the
independent survival strategies of multiple bacteria.
PMID- 29963631
TI - Network structure of the human musculoskeletal system shapes neural interactions
on multiple time scales.
AB - Human motor control requires the coordination of muscle activity under the
anatomical constraints imposed by the musculoskeletal system. Interactions within
the central nervous system are fundamental to motor coordination, but the
principles governing functional integration remain poorly understood. We used
network analysis to investigate the relationship between anatomical and
functional connectivity among 36 muscles. Anatomical networks were defined by the
physical connections between muscles, and functional networks were based on
intermuscular coherence assessed during postural tasks. We found a modular
structure of functional networks that was strongly shaped by the anatomical
constraints of the musculoskeletal system. Changes in postural tasks were
associated with a frequency-dependent reconfiguration of the coupling between
functional modules. These findings reveal distinct patterns of functional
interactions between muscles involved in flexibly organizing muscle activity
during postural control. Our network approach to the motor system offers a unique
window into the neural circuitry driving the musculoskeletal system.
PMID- 29963632
TI - Geomorphic expression of rapid Holocene silicic magma reservoir growth beneath
Laguna del Maule, Chile.
AB - Large rhyolitic volcanoes pose a hazard, yet the processes and signals
foretelling an eruption are obscure. Satellite geodesy has revealed surface
inflation signaling unrest within magma reservoirs underlying a few rhyolitic
volcanoes. Although seismic, electrical, and potential field methods may
illuminate the current configuration and state of these reservoirs, they cannot
fully address the processes by which they grow and evolve on geologic time
scales. We combine measurement of a deformed paleoshore surface, isotopic dating
of volcanism and surface exposure, and modeling to determine the rate of growth
of a rhyolite-producing magma reservoir. The numerical approach builds on a magma
intrusion model developed to explain the current, decade-long, surface inflation
at >20 cm/year. Assuming that the observed 62-m uplift reflects several non
eruptive intrusions of magma, each similar to the unrest over the past decade, we
find that ~13 km3 of magma recharged the reservoir at a depth of ~7 km during the
Holocene, accompanied by the eruption of ~9 km3 of rhyolite. The long-term rate
of magma input is consistent with reservoir freezing and pluton formation. Yet,
the unique set of observations considered here implies that large reservoirs can
be incubated and grow at shallow depth via episodic high-flux magma injections.
These replenishment episodes likely drive rapid inflation, destabilize cooling
systems, propel rhyolitic eruptions, and thus should be carefully monitored.
PMID- 29963633
TI - Inward growth by nucleation: Multiscale self-assembly of ordered membranes.
AB - Striking morphological similarities found between superstructures of a wide
variety of seemingly unrelated crystalline membrane systems hint at the existence
of a common formation mechanism. Resembling systems such as multiwalled carbon
nanotubes, bacterial protein shells, or peptide nanotubes, the self-assembly of
SDS/beta-cyclodextrin complexes leads to monodisperse multilamellar microtubes.
We uncover the mechanism of this hierarchical self-assembly process by time
resolved small- and ultrasmall-angle x-ray scattering. In particular, we show
that symmetric crystalline bilayers bend into hollow cylinders as a consequence
of membrane line tension and an anisotropic elastic modulus. Starting from single
walled microtubes, successive nucleation of new cylinders inside preexisting ones
drives an inward growth. As both the driving forces that underlie the self
assembly behavior and the resulting morphologies are common to systems of ordered
membranes, we believe that this formation mechanism has a similarly general
applicability.
PMID- 29963634
TI - Passive radiofrequency x-ray dosimeter tag based on flexible radiation-sensitive
oxide field-effect transistor.
AB - Distributed x-ray radiation dosimetry is crucial in diverse security areas with
significant environmental and human impacts such as nuclear waste management,
radiotherapy, or radioprotection devices. We present a fast, real-time dosimetry
detection system based on flexible oxide thin-film transistors that show a
quantitative shift in threshold voltage of up to 3.4 V/gray upon exposure to
ionizing radiation. The transistors use indium-gallium-zinc-oxide as a
semiconductor and a multilayer dielectric based on silicon oxide and tantalum
oxide. Our measurements demonstrate that the threshold voltage shift is caused by
the accumulation of positive ionization charge in the dielectric layer due to
high-energy photon absorption in the high-Z dielectric. The high mobility
combined with a steep subthreshold slope of the transistor allows for fast,
reliable, and ultralow-power readout of the deposited radiation dose. The order
of-magnitude variation in transistor channel impedance upon exposure to radiation
makes it possible to use a low-cost, passive radiofrequency identification sensor
tag for its readout. In this way, we demonstrate a passive, programmable,
wireless sensor that reports in real time the excess of critical radiation doses.
PMID- 29963635
TI - A general printing approach for scalable growth of perovskite single-crystal
films.
AB - Perovskite single-crystal films, which exhibit exceptionally low trap density and
nearly perfect translational symmetry, are believed to achieve the highest
performance of perovskite-based optoelectronic devices. However, fabrication of
these perovskite single-crystal films is quite difficult because of the
uncontrollable nucleation caused by the rapid reaction of two perovskite
precursors. We report a facile seed printing approach to selectively create
millimeter-sized perovskite single-crystal films with controlled thickness and
high yield. We show that perovskite single-crystal films can be perfectly
transferred to almost arbitrary substrates through the printing process. The as
grown perovskite single-crystal films have excellent crystalline quality and
morphology. We further demonstrate that perovskite single-crystal films can be
directly printed for scalable fabrication of photodetectors and effective image
sensors. This strategy allows high-yield fabrication of large perovskite single
crystal films for functional devices and may extend to other solution-processed
materials for wide applications.
PMID- 29963636
TI - Sampling molecular conformations and dynamics in a multiuser virtual reality
framework.
AB - We describe a framework for interactive molecular dynamics in a multiuser virtual
reality (VR) environment, combining rigorous cloud-mounted atomistic physics
simulations with commodity VR hardware, which we have made accessible to readers
(see isci.itch.io/nsb-imd). It allows users to visualize and sample, with atomic
level precision, the structures and dynamics of complex molecular structures "on
the fly" and to interact with other users in the same virtual environment. A
series of controlled studies, in which participants were tasked with a range of
molecular manipulation goals (threading methane through a nanotube, changing
helical screw sense, and tying a protein knot), quantitatively demonstrate that
users within the interactive VR environment can complete sophisticated molecular
modeling tasks more quickly than they can using conventional interfaces,
especially for molecular pathways and structural transitions whose conformational
choreographies are intrinsically three-dimensional. This framework should
accelerate progress in nanoscale molecular engineering areas including
conformational mapping, drug development, synthetic biology, and catalyst design.
More broadly, our findings highlight the potential of VR in scientific domains
where three-dimensional dynamics matter, spanning research and education.
PMID- 29963637
TI - Microscopy with a single-molecule scanning electrometer.
AB - The vibrational spectrum of a single carbon monoxide molecule, adsorbed on the
tip apex of a scanning tunneling microscope, is used to image electrostatic
fields with submolecular spatial resolution. The method takes advantage of the
vibrational Stark effect to image local electrostatic fields and the single
molecule sensitivity of tip-enhanced Raman scattering (TERS) to optically relay
the signal. We apply the method to single metalloporphyrins adsorbed on Au(111)
to image molecular charges, intramolecular polarization, local photoconductivity,
atomically resolved hydrogen bonds, and surface electron density waves.
PMID- 29963638
TI - Analyzing Volatile Anesthetic Consumption by Auditing Fresh Gas Flow: An
Observational Study at an Academic Hospital.
AB - Background: In a climate of cost containment, it is critical to analyze and
optimize all perioperative variable costs. Fresh gas flow is one important
variable that determines utilization of inhalational agents and can be tightly
controlled by the anesthesia provider. Manufacturers of inhalational agents have
recommendations for minimum gas flow for their respective agents. Any gas flow
above these recommendations is considered misuse and leads to unnecessary
expense. The purpose of this study was to characterize and quantify the excess
use of inhalational agents by analyzing fresh gas flow rates for long duration
cases. Methods: Over a span of three months, operating room records were analyzed
for all procedures lasting greater than 4 hours. End tidal inhalation agent
percentage for Sevoflurane and Isoflurane and fresh gas flows were analyzed. 303
unique patients with at least 4 hours of anesthesia time were included. Analysis
excluded the first and last 30 minutes of all anesthetics to account for need for
higher gas flows during induction/emergence of anesthesia. 152 patients received
sevoflurane alone. 33 patients received isoflurane alone. 107 patients received
both isoflurane and sevoflurane and were included in sevoflurane group given the
higher gas flow needs of sevoflurane. 11 patients received neither agent and were
excluded from analysis. We proceed with n = 292 unique patients. (259 in Sevo, 33
in iso) We used the two-sided one sample t-test setting 2 ml/min as the null for
sevo and 1 ml/min as the null for iso; we ran analysis using a nonparametric test
that didn't require the fresh gas flow to be normally distributed - the two-sided
one-sample Wilcoxon rank-sum test: p value = < 0.0001. Results: The results of
our study revealed a sevoflurane (n = 259) mean fresh gas flow (L/min) 2.55 (95%
CI, 2.45-2.66) - significantly different from null of 2 ml/min (p < 0.0001).
Isoflurane (n = 33) mean fresh gas flows (L/min) 2.33 (95% CI, 2.00-2.66) -
significantly different from null of 1 l/min (p < 0.0001). Conclusion:
Manufacturer recommendation for sevoflurane is to maintain gas flows 1-2 l/min
and Isoflurane at above 1 l/min. Given these recommendations, the anesthesia
providers delivered fresh gas flows at least 28% higher than necessary for
sevoflurane and at least 130% greater than necessary for isoflurane anesthetics
that lasted greater than 4 hours. This is an area where cost reduction can be
readily achieved. Future plans to realize a reduction in inhalational agent
utilization include education of the benefits of fresh gas flow and instituting a
low fresh gas flow policy.
PMID- 29963640
TI - Identification of Pathogenicity-Associated Loci in Klebsiella pneumoniae from
Hospitalized Patients.
AB - Despite insights gained through experimental models, the set of bacterial genes
important for human infection is unclear for many of our most threatening
pathogens. Klebsiella pneumoniae is a leading cause of health care-associated
infections (HAIs) and commonly colonizes hospitalized patients, but the factors
that determine whether a particular isolate causes disease or remains a colonizer
are poorly understood. To identify bacterial genes associated with K. pneumoniae
infection, a case-control study was performed comparing infected and asymptomatic
colonized patients. Comparative bacterial genomics was combined with a
conditional logit model that identified patient factors differentiating cases
from controls. This method identified five gene loci associated with infection
after adjustment for patient factors, including a psicose sugar utilization locus
that was validated as a fitness factor during mouse lung infection. These results
indicate that bacterial genome-wide association studies of patients can identify
loci associated with HAIs and important in infection models. IMPORTANCE
Klebsiella pneumoniae is a common cause of infections in the health care setting.
This work supports a paradigm for K. pneumoniae pathogenesis where the accessory
genome, composed of genes present in some but not all isolates, influences
whether a strain causes infection or asymptomatic colonization, after accounting
for patient-level factors. Identification of patients at high risk of infection
could allow interventions to prevent or rapidly treat K. pneumoniae infections.
PMID- 29963639
TI - Asymptomatic Intestinal Colonization with Protist Blastocystis Is Strongly
Associated with Distinct Microbiome Ecological Patterns.
AB - Blastocystis is the most prevalent protist of the human intestine, colonizing
approximately 20% of the North American population and up to 100% in some
nonindustrialized settings. Blastocystis is associated with gastrointestinal and
systemic disease but can also be an asymptomatic colonizer in large populations.
While recent findings in humans have shown bacterial microbiota changes
associated with this protist, it is unknown whether these occur due to the
presence of Blastocystis or as a result of inflammation. To explore this, we
evaluated the fecal bacterial and eukaryotic microbiota in 156 asymptomatic adult
subjects from a rural population in Xoxocotla, Mexico. Colonization with
Blastocystis was strongly associated with an increase in bacterial alpha
diversity and broad changes in beta diversity and with more discrete changes to
the microbial eukaryome. More than 230 operational taxonomic units (OTUs),
including those of dominant species Prevotella copri and Ruminococcus bromii,
were differentially abundant in Blastocystis-colonized individuals. Large
functional changes accompanied these observations, with differential abundances
of 202 (out of 266) predicted metabolic pathways (PICRUSt), as well as lower
fecal concentrations of acetate, butyrate, and propionate in colonized
individuals. Fecal calprotectin was markedly decreased in association with
Blastocystis colonization, suggesting that this ecological shift induces
subclinical immune consequences to the asymptomatic host. This work is the first
to show a direct association between the presence of Blastocystis and shifts in
the gut bacterial and eukaryotic microbiome in the absence of gastrointestinal
disease or inflammation. These results prompt further investigation of the role
Blastocystis and other eukaryotes play within the human microbiome. IMPORTANCE
Given the results of our study and other reports of the effects of the most
common human gut protist on the diversity and composition of the bacterial
microbiome, Blastocystis and, possibly, other gut protists should be studied as
ecosystem engineers that drive community diversity and composition.
PMID- 29963641
TI - Characterization of Wild and Captive Baboon Gut Microbiota and Their Antibiotic
Resistomes.
AB - Environmental microbes have harbored the capacity for antibiotic production for
millions of years, spanning the evolution of humans and other vertebrates.
However, the industrial-scale use of antibiotics in clinical and agricultural
practice over the past century has led to a substantial increase in exposure of
these agents to human and environmental microbiota. This perturbation is
predicted to alter the ecology of microbial communities and to promote the
evolution and transfer of antibiotic resistance (AR) genes. We studied wild and
captive baboon populations to understand the effects of exposure to humans and
human activities (e.g., antibiotic therapy) on the composition of the primate
fecal microbiota and the antibiotic-resistant genes that it collectively harbors
(the "resistome"). Using a culture-independent metagenomic approach, we
identified functional antibiotic resistance genes in the gut microbiota of wild
and captive baboon groups and saw marked variation in microbiota architecture and
resistomes across habitats and lifeways. Our results support the view that
antibiotic resistance is an ancient feature of gut microbial communities and that
sharing habitats with humans may have important effects on the structure and
function of the primate microbiota. IMPORTANCE Antibiotic exposure results in
acute and persistent shifts in the composition and function of microbial
communities associated with vertebrate hosts. However, little is known about the
state of these communities in the era before the widespread introduction of
antibiotics into clinical and agricultural practice. We characterized the fecal
microbiota and antibiotic resistomes of wild and captive baboon populations to
understand the effect of human exposure and to understand how the primate
microbiota may have been altered during the antibiotic era. We used culture
independent and bioinformatics methods to identify functional resistance genes in
the guts of wild and captive baboons and show that exposure to humans is
associated with changes in microbiota composition and resistome expansion
compared to wild baboon groups. Our results suggest that captivity and lifestyle
changes associated with human contact can lead to marked changes in the ecology
of primate gut communities.
PMID- 29963643
TI - Molecular analysis of endotracheal tube biofilms and tracheal aspirates in the
pediatric intensive care unit.
AB - Background: Ventilator-associated pneumonia (VAP) is a known complication of
mechanically ventilated children in the pediatric intensive care unit (PICU).
Endotracheal tube (ETT) biofilms are often implicated in the development of VAP
by providing a conduit for pathogens to the lower respiratory tract. Methods: A
prospective cohort study from April 2010-March 2011 of children 4 weeks to 18
years of age ventilated for greater than 72 hours to determine the microbiota of
ETT biofilms and tracheal aspirates. Results: Thirty-three patients were included
with a mean age of 6.1 years (SD +/- 5.1 years) and average length of intubation
of 8.8 days (SD +/- 5.0 days). Bacterial communities from tracheal aspirates and
the proximal and distal ends of ETTs were determined using 16S rRNA gene
libraries. Statistical analysis utilized two-part statistics and the Wilcoxon
signed rank sum test for comparison of bacterial communities. Sequencing revealed
a predominance of oropharyngeal microbiota including Prevotella and Streptococcus
spp. Pathogenic bacterial genera including Staphylococcus, Burkholderia,
Moraxella, and Haemophilus were also represented. Bacterial load was greatest at
the proximal aspect of the ETT. Duration of intubation did not significantly
impact bacterial load. Morisita Horn analysis across sites showed similar
communities in 24/33 (72%) of patients. Conclusions: ETT biofilms and tracheal
aspirates of intubated patients in the PICU primarily consisted of oropharyngeal
microbiota, but had a significant representation of potentially pathogenic
genera. While the majority of patients had similar microbiota when comparing
their ETT biofilms and tracheal aspirates, a subset of patients showed a
divergence between communities that requires further investigation.
PMID- 29963642
TI - Huntington's Disease-Induced Cardiac Disorders Affect Multiple Cellular Pathways.
AB - Huntington's disease (HD) is a rare, inherited, progressive, and fatal
neurological disorder resulting from expanded polyglutamine repeats in the
huntingtin protein. While HD is predominately characterized as a disease of the
central nervous system, mortality surveys and epidemiological studies reveal
heart disease as one of the leading causes of death in HD patients. Emerging
evidence supports a link between HD and cardiovascular disease, such as cardiac
amyloidosis (accumulation of aggregates in the heart). Experimental animal and
clinical studies have attempted to explain the mechanisms of HD-induced cardiac
pathology in the association of protein misfolding, autophagic defects, oxidative
stress, mitochondrial dysfunction, and cell death. HD is increasingly understood
as a complex disease with peripheral components of cardiac and skeletal muscle
pathophysiology. While the discovery of these linkages and apparent pathological
markers is promising, the mechanism of HD-induced cardiac pathology and the
nature of its cell autonomy remain elusive. Further study of the wide-ranging
cardiac function in HD patients is needed. This review highlights published
literature on the pathological factors associated with HD-induced cardiac
amyloidosis and other cardiovascular diseases, and addresses gaps in this
expanding area of study. Through comprehensive experimental and clinical studies,
potential drugs can be tested to attenuate and/or ameliorate HD-induced cardiac
pathology and mortality.
PMID- 29963644
TI - LncRNAs in genetic basis of glaucoma.
AB - Glaucoma is an umbrella term used to designate a heterogeneous group of ocular
disorders characterised by progressive excavation of the optic disc, optic
atrophy and gradual loss of the visual field caused by the slow death of retinal
ganglion cells and their axons. Glaucoma can potentially lead to blindness if
left untreated. It usually starts from the periphery and progresses gradually
toward the centre of the visual field. Vision loss caused by glaucoma is
irreversible and causes a heavy burden on affected families and society,
therefore the importance of early diagnosis and prevention should be emphasised.
Genetic factors appear to play a role in glaucoma pathogenesis; it has been shown
that individuals with a positive family history are at a greater risk because
they are more likely predisposed be affected. Notable advances have been recorded
in the past decade concerning the genetic and environmental factors likely to
contribute or cause glaucoma with the discovery of multiple glaucoma-associated
genes and genetic loci. Thorough investigations by a handful of studies on the
function of long non-coding RNAs discovered that, although lacking protein-coding
potential, lncRNAs can still participate in the regulation of gene expression at
various levels, thus their possible implication in different disease aetiologies.
In this review, we focus on the lncRNAs characteristics and its regulation, and
summarise these results from separate, independent, glaucoma-related studies in
addition to discussing possible pathways by which lncRNAs might contribute to
glaucoma.
PMID- 29963646
TI - Persistent neuronal activity in human prefrontal cortex links perception and
action.
AB - How do humans flexibly respond to changing environmental demands on a sub-second
temporal scale? Extensive research has highlighted the key role of the prefrontal
cortex in flexible decision-making and adaptive behavior, yet the core mechanisms
that translate sensory information into behavior remain undefined. Utilizing
direct human cortical recordings, we investigated the temporal and spatial
evolution of neuronal activity, indexed by the broadband gamma signal, while
sixteen participants performed a broad range of self-paced cognitive tasks. Here
we describe a robust domain- and modality-independent pattern of persistent
stimulus-to-response neural activation that encodes stimulus features and
predicts motor output on a trial-by-trial basis with near-perfect accuracy.
Observed across a distributed network of brain areas, this persistent neural
activation is centered in the prefrontal cortex and is required for successful
response implementation, providing a functional substrate for domain-general
transformation of perception into action, critical for flexible behavior.
PMID- 29963645
TI - Digital eye strain: prevalence, measurement and amelioration.
AB - Digital device usage has increased substantially in recent years across all age
groups, so that extensive daily use for both social and professional purposes is
now normal. Digital eye strain (DES), also known as computer vision syndrome,
encompasses a range of ocular and visual symptoms, and estimates suggest its
prevalence may be 50% or more among computer users. Symptoms fall into two main
categories: those linked to accommodative or binocular vision stress, and
external symptoms linked to dry eye. Although symptoms are typically transient,
they may be frequent and persistent, and have an economic impact when vocational
computer users are affected. DES may be identified and measured using one of
several available questionnaires, or objective evaluations of parameters such as
critical flicker-fusion frequency, blink rate and completeness, accommodative
function and pupil characteristics may be used to provide indices of visual
fatigue. Correlations between objective and subjective measures are not always
apparent. A range of management approaches exist for DES including correction of
refractive error and/or presbyopia, management of dry eye, incorporating regular
screen breaks and consideration of vergence and accommodative problems. Recently,
several authors have explored the putative role of blue light-filtering spectacle
lenses on treating DES, with mixed results. Given the high prevalence of DES and
near-universal use of digital devices, it is essential that eye care
practitioners are able to provide advice and management options based on quality
research evidence.
PMID- 29963648
TI - Homocysteine, B Vitamins, MTHFR Genotype, and Incident Age-related Macular
Degeneration.
PMID- 29963647
TI - l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats
Through Activation of the GCH1-GFRP Complex.
AB - Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular
function. NO is extremely labile and has been challenging to develop as a
therapeutic agent. However, NO bioavailability could be enhanced by
pharmacologically targeting endogenous NO regulatory pathways.
Tetrahydrobiopterin, an essential cofactor for NO production, is synthesized by
GTP cyclohydrolase-1 (GCH1), which complexes with GCH1 feedback regulatory
protein (GFRP). The dietary amino acid l-phenylalanine activates this complex,
elevating vascular BH4. Here, the authors demonstrate that l-phenylalanine
administration restores vascular function in a rodent model of hypertension,
suggesting the GCH1-GFRP complex represents a rational therapeutic target for
diseases underpinned by endothelial dysfunction.
PMID- 29963649
TI - Regulation of microdomain voltage-gated L-type calcium channels in cardiac health
and disease.
AB - Cav1.2 channels in the heart mediate excitation-contraction (E-C) coupling; tune
cardiac excitability; and regulate gene expression. In ventricular myocytes,
CaV1.2 channels are predominantly located in t-tubules where they are in
proximity to ryanodine receptors to trigger cardiac E-C coupling. A subset of
ventricular CaV1.2 channels existing on the surface sarcolemma, including in
caveolae, have less well-defined functions. Cardiac CaV1.2 channels are famously
up-regulated by protein kinase A as a component of the 'fight-or-flight'
response. The molecular details of how this kinase regulates cardiac CaV1.2
channels are controversial and under intensive study. Here, we critically review
recent work addressing the putative functions of microdomain cardiac CaV1.2
channels, and their regulation by distinct kinases in health and disease.
PMID- 29963650
TI - Disks around merging binary black holes: From GW150914 to supermassive black
holes.
AB - We perform magnetohydrodynamic simulations in full general relativity of disk
accretion onto nonspinning black hole binaries with mass ratio q = 29/36. We
survey different disk models which differ in their scale height, total size and
magnetic field to quantify the robustness of previous simulations on the initial
disk model. Scaling our simulations to LIGO GW150914 we find that such systems
could explain possible gravitational wave and electromagnetic counterparts such
as the Fermi GBM hard x-ray signal reported 0.4 s after GW150915 ended. Scaling
our simulations to supermassive binary black holes, we find that observable flow
properties such as accretion rate periodicities, the emergence of jets throughout
inspiral, merger and postmerger, disk temperatures, thermal frequencies, and the
time delay between merger and the boost in jet outflows that we reported in
earlier studies display only modest dependence on the initial disk model we
consider here.
PMID- 29963651
TI - Characterization of Covalent-Reversible EGFR Inhibitors.
AB - Within the spectrum of kinase inhibitors, covalent-reversible inhibitors (CRIs)
provide a valuable alternative approach to classical covalent inhibitors. This
special class of inhibitors can be optimized for an extended drug-target
residence time. For CRIs, it was shown that the fast addition of thiols to
electron-deficient olefins leads to a covalent bond that can break reversibly
under proteolytic conditions. Research groups are just beginning to include CRIs
in their arsenal of compound classes, and, with that, the understanding of this
interesting set of chemical warheads is growing. However, systems to assess both
characteristics of the covalent-reversible bond in a simple experimental setting
are sparse. Here, we have developed an efficient methodology to characterize the
covalent and reversible properties of CRIs and to investigate their potential in
targeting clinically relevant variants of the receptor tyrosine kinase EGFR.
PMID- 29963652
TI - Early Life Stress Associated With Increased Striatal N-Acetyl-Aspartate:
Cerebrospinal Fluid Corticotropin-Releasing Factor Concentrations, Hippocampal
Volume, Body Mass and Behavioral Correlates.
AB - Introduction: Using proton magnetic resonance spectroscopy imaging (1H-MRSI), the
effects of early life stress (ELS) on nonhuman primate striatal neuronal
integrity were examined as reflected by N-acetyl aspartate (NAA) concentrations.
NAA measures were interrogated through examining their relationship to previously
documented ELS markers -- cerebrospinal fluid (CSF) corticotropin-releasing
factor (CRF) concentrations, hippocampal volume, body mass and behavioral
timidity. Rodent models of depression exhibit increases in neurotrophic effects
in the nucleus accumbens (NAcc). We hypothesized that rearing under conditions of
ELS [Variable Foraging Demand: (VFD)] would produce persistent elevations of NAA
concentrations (in absolute or ratio form) in ventral striatum/caudate nucleus
(VS/CN) with altered correlation to ELS markers. Methods: Eleven bonnet macaque
males reared under VFD conditions and seven age-matched control subjects
underwent 1H-MRSI during young adulthood. Voxels were placed over ventral
striatum/caudate nucleus (VS/CN) to capture NAcc. Cisternal CSF CRF
concentrations, hippocampal volume, body mass and response to a human intruder
had been previously determined. Results: VFD-reared monkeys exhibited
significantly increased NAA/Cr concentrations in right VS/CN in comparison to
normally-reared controls, controlling for multiple comparisons. In comparison to
controls, VFD CSF CRF concentrations were directly associated with right VS/CN
absolute NAA. Left hippocampal volume was inversely associated with left VS/CN N
acetyl aspartate/creatine (NAA/Cr) in VFD-reared but not in controls. Disruption
of a normative inverse correlation between left VS/CN NAA and body mass was noted
in VFD. Only non-VFD subjects exhibited a direct relationship between timidity
response to an intruder and right VS/CN NAA. Conclusion: ELS produced persistent
increases in VS/CN NAA, which demonstrated specific patterns of association (or
lack thereof) to ELS markers in comparison to non-VFD subjects. The data are
broadly consistent with a stable nonhuman primate phenotype of anxiety and mood
disorder vulnerability whereby in vivo indicators of neuronal integrity, although
reduced in hippocampus, are increased in striatum. The findings may provide a
catalyst for further studies in humans and other species regarding a reciprocal
hippocampal/NAcc relationship in affective disorders.
PMID- 29963653
TI - Developing an objective assessment of surgical performance from operating room
video and surgical imagery.
AB - An unbiased, repeatable process for assessing operating room performance is an
important step toward quantifying the relationship between surgical training and
performance. Hip fracture surgeries offer a promising first target in orthopedic
trauma because they are common and they offer quantitative performance metrics
that can be assessed from video recordings and intraoperative fluoroscopic
images. Hip fracture repair surgeries were recorded using a head-mounted point-of
view camera. Intraoperative fluoroscopic images were also saved. The following
performance metrics were analyzed: duration of wire navigation, number of
fluoroscopic images collected, degree of intervention by the surgeon's
supervisor, and the tip-apex distance (TAD). Two orthopedic traumatologists
graded surgical performance in each video independently using an Objective
Structured Assessment of Technical Skill (OSATS). Wire navigation duration
correlated with weeks into residency and prior cases logged. TAD correlated with
cases logged. There was no significant correlation between the OSATS total score
and experience metrics. Total OSATS score correlated with duration and number of
fluoroscopic images. Our results indicate that two metrics of hip fracture wire
navigation performance, duration and TAD, significantly differentiate surgical
experience. The methods presented have the potential to provide truly objective
assessment of resident technical performance in the OR.
PMID- 29963654
TI - Hypothesizing Las Vegas and Sutherland Springs Mass Shooters Suffer from Reward
Deficiency Syndrome: "Born Bad".
AB - The slaughters in Las Vegas and Sutherland Springs demand explanation, in the
face of the ineffable. An understanding of the shooters' motives could restore
our trust in our mutually cooperative existence. In this short communication we
provide post-hoc rationale of both Stephen Paddock (Las Vegas mass shooting) and
Devin Kelley (Southerland Springs mass shooting) and hypothesize that these
shooters had genetically induced "Reward Deficiency Syndrome" (RDS) and a
hypodopaminergia trait/state. In this particular case we are in pursuit of trying
to obtain postmortem samples of mass shooters for subsequent epigenetic and
neurogenetic analyses. It is our contention that early genetic identification of
RDS and its pathological behaviors including hyper - sexuality, violence, a love
for guns, even in children, could be a giant step forward in potentially saving
lives.
PMID- 29963656
TI - All-Organic Textile Thermoelectrics with Carbon-Nanotube-Coated n-Type Yarns.
AB - Thermoelectric textiles that are able to generate electricity from heat gradients
may find use as power sources for a wide range of miniature wearable electronics.
To realize such thermoelectric textiles, both p- and n-type yarns are needed. The
realization of air-stable and flexible n-type yarns, i.e., conducting yarns where
electrons are the majority charge carriers, presents a considerable challenge due
to the scarcity of air-stable n-doped organic materials. Here, we realize such n
type yarns by coating commercial sewing threads with a nanocomposite of
multiwalled carbon nanotubes (MWNTs) and poly(N-vinylpyrrolidone) (PVP). Our n
type yarns have a bulk conductivity of 1 S cm-1 and a Seebeck coefficient of -14
MUV K-1, which is stable for several months at ambient conditions. We combine our
coated n-type yarns with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)
(PEDOT:PSS) dyed silk yarns, constituting the p-type component, to realize a
textile thermoelectric module with 38 n/p elements, which are capable of
producing an open-circuit voltage of 143 mV when exposed to a temperature
gradient of 116 degrees C and a maximum power output of 7.1 nW at a temperature
gradient of 80 degrees C.
PMID- 29963655
TI - Inhibiting tumor necrosis factor-alpha at time of induced intervertebral disc
injury limits long-term pain and degeneration in a rat model.
AB - Background: Painful intervertebral disc (IVD) degeneration has tremendous
societal costs and few effective therapies. Intradiscal tumor necrosis factor
alpha (TNFalpha) is commonly associated with low back pain, but the direct
relationship remains unclear. Purpose: Treatment strategies for low back pain
require improved understanding of the complex relationships between pain,
intradiscal pro-inflammatory cytokines, and structural IVD degeneration. A rat in
vivo lumbar IVD puncture model was used to 1) determine the role of TNFalpha in
initiating painful IVD degeneration, and 2) identify statistical relationships
between painful behavior, IVD degeneration, and intradiscal pro-inflammatory
cytokine expression. Methods: Lumbar IVDs were punctured anteriorly and injected
with TNFalpha, anti-TNFalpha, or saline and compared with sham and naive
controls. Hindpaw mechanical hyperalgesia was assayed weekly to determine pain
over time. 6-weeks post-surgery, animals were sacrificed, and IVD degeneration,
IVD height, and intradiscal TNFalpha and interleukin-1 beta (IL-1beta)
expressions were assayed. Results: Intradiscal TNFalpha injection increased pain
and IVD degeneration whereas anti-TNFalpha alleviated pain to sham level.
Multivariate step-wise linear regression identified pain threshold was predicted
by IVD degeneration and intradiscal TNFalpha expression. Pain threshold was also
linearly associated with IVD height loss and IL-1beta. Discussion: The
significant associations between IVD degeneration, height loss, inflammation, and
painful behavior highlight the multifactorial nature of painful IVD degeneration
and the challenges to diagnose and treat a specific underlying factor. We
concluded that TNFalpha is an initiator of painful IVD degeneration and its early
inhibition can mitigate pain and degeneration. Intradiscal TNFalpha inhibition
following IVD injury may warrant investigation for its potential to alter
downstream painful IVD degeneration processes.
PMID- 29963658
TI - An efficient and recyclable ionic diphosphine-based Ir-catalyst for
hydroaminomethylation of olefins with H2O as the hydrogen source.
AB - Hydroaminomethylation of olefins with H2O as the hydrogen source was accomplished
over an Ir-catalyst with the involvement of an ionic diphosphine (L6). The use of
H2O as the hydrogen source could completely inhibit the hydrogenation of olefins.
The pi-accepting ability and improved stability of L6 endowed the corresponding
Ir-catalyst with high activity and good longevity for recycling uses.
PMID- 29963659
TI - Uniform poly(phosphazene-triazine) porous microspheres for highly efficient
iodine removal.
AB - Rich heteroatom-doped conjugated nanoporous polymers with uniform microspherical
morphology exhibit remarkably high capacity up to 450 wt% for removing iodine
from the vapor phase (at 348 K and atmospheric pressure).
PMID- 29963657
TI - Regulation of microtubule dynamic instability by the carboxy-terminal tail of
beta-tubulin.
AB - Dynamic instability is an intrinsic property of microtubules; however, we do not
understand what domains of alphabeta-tubulins regulate this activity or how these
regulate microtubule networks in cells. Here, we define a role for the negatively
charged carboxy-terminal tail (CTT) domain of beta-tubulin in regulating dynamic
instability. By combining in vitro studies with purified mammalian tubulin and in
vivo studies with tubulin mutants in budding yeast, we demonstrate that beta
tubulin CTT inhibits microtubule stability and regulates the structure and
stability of microtubule plus ends. Tubulin that lacks beta-tubulin CTT
polymerizes faster and depolymerizes slower in vitro and forms microtubules that
are more prone to catastrophe. The ends of these microtubules exhibit a more
blunted morphology and rapidly switch to disassembly after tubulin depletion. In
addition, we show that beta-tubulin CTT is required for magnesium cations to
promote depolymerization. We propose that beta-tubulin CTT regulates the assembly
of stable microtubule ends and provides a tunable mechanism to coordinate dynamic
instability with ionic strength in the cell.
PMID- 29963660
TI - P-Doped carbons derived from cellulose as highly efficient metal-free catalysts
for aerobic oxidation of benzyl alcohol in water under an air atmosphere.
AB - P-Doped carbons, prepared by carbonizing phosphoric acid-treated cellulose,
exhibit high catalytic activity in metal-free aerobic oxidation of benzyl alcohol
to benzaldehyde (99.7% yield) in water under air. A high turnover frequency is
obtained due to the doped P-species of C3PO, identified via experiments and DFT
calculations.
PMID- 29963661
TI - Mechanism of the thermal decomposition of tetramethylsilane: a flash pyrolysis
vacuum ultraviolet photoionization time-of-flight mass spectrometry and density
functional theory study.
AB - The thermal decomposition of tetramethylsilane (TMS) was studied over the
temperature range of 298-1450 K by combining flash pyrolysis vacuum ultraviolet
photoionization time-of-flight mass spectrometry (VUV-PI-TOFMS) and density
functional theory (DFT). The initial step in TMS pyrolysis produced a methyl
radical (Me) and Me3Si. Me3Si underwent subsequent loss of a hydrogen atom to
form Me2Si[double bond, length as m-dash]CH2 and loss of a methyl radical to form
Me2Si:. Isomerizations via 1,2-shift and H2 eliminations were major secondary
decomposition reactions of Me2Si[double bond, length as m-dash]CH2 and Me2Si:.
Among the various isomers, silylene species containing Si-H bonds, such as
:Si(H)CH2CH2CH3, :Si(H)CH2CH[double bond, length as m-dash]CH2, :Si(H)CH2CH3, and
:Si(H)CH[double bond, length as m-dash]CH2, played an important role in H2
elimination reactions. On the other hand, silene species were insignificant in H2
eliminations. Unlike the silylene species, H2 elimination of :Si[double bond,
length as m-dash]CH2 was energetically unfavorable.
PMID- 29963662
TI - Peptides derived from the histidine-proline rich glycoprotein bind copper ions
and exhibit anti-angiogenic properties.
AB - The role of copper in cancer progression has been established since decades.
Additionally, copper is able to stimulate angiogenesis through the control of
VEGF expression and activity in endothelial cells. In this paper a tetrapeptide,
belonging to the histidine-proline-rich glycoprotein (HPRG) and encompassing four
repeats of the sequence GHHPH (named TetraHPRG), was synthesized and its
copper(ii) complex species were characterized by means of potentiometry, UV-vis,
circular dichroism (CD), electron paramagnetic resonance (EPR) and electron spray
ionization mass spectrometry (ESI-MS). Moreover, a peptide covalently bound
through an amidic bond to trehalose (TH-TetraHPRG) was designed and synthesized
as a prodrug system. The activity of both TetraHPRG and TH-TetraHPRG molecules on
copper and VEGF induced angiogenic responses in endothelial cells was assessed.
The two peptides show a similar and effective anti-angiogenic activity on both
molecular and cellular responses. Since the trehalose derivative has a higher
resistance to enzymatic degradation, it can be further exploited as a potential
drug delivery system with anti-angiogenic activity.
PMID- 29963663
TI - Hydrogen-free defects in hydrogenated black TiO2.
AB - Black anatase TiO2 has surprisingly enhanced solar energy harvesting efficiency
and electrical conductivity, which makes it a promising material in a wide range
of energy and environmental applications. Several experimental and theoretical
studies have successfully revealed the mechanisms of band gap reduction by
surface hydrogenation of anatase TiO2. However, recent experimental evidence
suggests the existence of bulk point defects that yield infrared (~1.0 eV)
photoabsorption and high conductivity of black anatase TiO2. In the current
study, using a combination of ab initio molecular dynamics simulations and
electronic structure calculations, we successfully explain the physical
properties, metallicity, and infrared/microwave absorption (i.e., black color) of
highly reduced anatase TiO2 crystal in a hydrogenated state with a newly found
pair defect (Tii-VO)4+. Hydrogen atoms in the bulk are unnecessary to understand
the observed properties.
PMID- 29963667
TI - Optical-reconfigurable carbon nanotube and indium-tin-oxide complementary thin
film transistor logic gates.
AB - Optically transparent thin-film transistors (TFTs) have recently attracted
significant attention for a new generation of transparent electronics where p-
and n-channel transistors form the basic building block for complementary analog
and digital integrated circuits (ICs). This paper reports a hybrid integration of
p-channel carbon nanotube (CNT) and n-channel junctionless indium-tin-oxide (ITO)
TFTs using a simple and cost-effective shadow mask-assisted fabrication process.
The fabricated devices exhibit a high transmittance of ~90% in the visible light
region and function as inverters, NAND and NOR gates. More interestingly,
distinct optoelectronic responses of the CNT- and ITO-TFTs to ultraviolet light
have been clearly observed. In addition to conventional electrically gated logic
operations, simple optical-reconfigurable logic operations have been realized
with hybrid CNT/ITO-TFT based logic gates. The results suggest that introducing
optical-modulation to the logic gates could increase the functionalities compared
with the traditional electrically driven counterparts.
PMID- 29963668
TI - Investigation of copper precursors in the synthesis of higher alcohols from
syngas over CuZnAl catalysts without promoters.
AB - The catalytic performances of different CuZnAl catalysts prepared using copper
nitrate, copper acetate and copper citrate for CO hydrogenation to higher
alcohols (C2+OH) were studied in a slurry bed reactor. Among these catalysts, the
Cu-N catalyst prepared using copper nitrate showed a relatively higher C2+OH
selectivity and no obvious deactivation occurred during the lifetime test for 120
h. The influence of copper precursors on the performance of the CuZnAl catalysts
was investigated by XRD, 27Al-MAS-NMR, N2 adsorption-desorption, H2-TPR, NH3-TPD,
FT-IR and XPS techniques. The results indicated that the size of Cu0 particles,
textural properties, the chemical state of Cu species, the amount of surface acid
and chemical composition varied, which led to diverse catalytic activities toward
C2+OH synthesis. It was concluded that Cu0, Cu+ and AlOOH were all necessary in
ethanol and C2+OH synthesis when using the CuZnAl catalysts without promoters and
the synergism of these species was beneficial to the formation of C2+OH. This
work further demonstrated that alkalis and Fischer-Tropsch elements were not
indispensable for C2+OH synthesis from syngas.
PMID- 29963671
TI - Three new high-nuclear transition-metal-substituted heteropolytungstates:
syntheses, crystal structures, magnetic studies and NLO properties.
AB - Three new nickel-cluster-substituted polyoxometalates (POMs), [Ni6(H2O)9(MU3
OH)3(HSiW9O34)]2.12H2O (1), [Ni(en)(H2O)3][Ni6(H2O)3(en)2L(MU3
OH)3(HSiW9O34)]2.9H2O (2) (en = ethylenediamine; L = C7H5O2 = benzoic acid) and
[Ni6(L')6(CH3COO)(H2O)3(MU3-OH)3(HPW9O34)]2.9H2O (3) (L' = C5NH5 = pyridine) were
successfully isolated under hydro-/solvothermal conditions. 1-3 were structurally
characterized by single-crystal XRD, elemental analyses, PXRD, IR, and TGA.
Compound 1 mainly consists of a pair of {Ni6SiW9} fragments and some water
molecules. Interestingly, the whole structure can be regarded as the connection
of {Ni6SiW9} and another unit rotated 180 degrees through Ni-O-W bonds, forming
a dimeric structure {Ni6SiW9}2. Compounds 2 and 3 also have an {Ni6XW9}2 (X = Si,
P) dimer, but there is a big difference in the connection between {Ni6SiW9}
units. On this basis, mono-dentate conjugated organic ligands (benzoic acid (L)
and pyridine (L')) were successfully introduced. It is noteworthy that pyridine
molecules were first integrated into {Ni6SiW9}-based clusters and 3 features the
highest number of organic ligands (six pyridines per Ni6) in the reported
{Ni6XW9}-based clusters. The introduction of organic ligands to compounds 2 and 3
can bring about better third-order nonlinear optical properties. Magnetic
research indicated the existence of ferromagnetic interactions in 2-3.
PMID- 29963672
TI - An azobenzene-based heteromeric prodrug for hypoxia-activated chemotherapy by
regulating subcellular localization.
AB - An azobenzene-based heteromeric prodrug (hNDP) was prepared for targeted
chemotherapy against hypoxic tumor. hNDP could divert the parent drug from
nucleus to cytoplasm with lower toxicity, while the azoreduction of hNDP in
hypoxia would activate the drug with a robust anti-tumor effect by initiating the
apoptosis-related biochemical cascades.
PMID- 29963673
TI - Highly durable and cycle-stable lithium storage based on MnO nanoparticle
decorated 3D interconnected CNT/graphene architecture.
AB - To accommodate huge volume change and boost the inferior electrochemical reaction
kinetics of manganous oxide anodes for lithium-ion batteries, a unique 3D porous
CNT/graphene-MnO architecture has been synthesized, with MnO nanoparticles
homogeneously decorated on 3D interconnected CNT/graphene (3DCG) conductive
networks. This porous 3DCG matrix with its abundant open pores and large surface
area can provide efficient channels for fast charge transport and allow full
contact between the electrode and electrolyte, leading to improved
electrochemical activity. The robust 3D architecture offers abundant stress
buffer space to tolerate volume expansion and ensures robust structural stability
during the electrochemical processes. The synergistic effect between components
endows the 3DCG/MnO electrodes with excellent electrochemical performance,
retaining a high specific capacity of 526.7 mA h g-1 at 2.0 A g-1 with 98%
capacity retention over 1400 cycles. This work provides a promising route for the
practical application of fast and durable lithium-ion batteries and suggests
insights for rational structural designs with other transition metal oxides.
PMID- 29963674
TI - A facile approach for preparing densely-packed individual p-NiO/n-Fe2O3
heterojunction nanowires for photoelectrochemical water splitting.
AB - Innovative design of electrode materials is crucial for efficient conversion of
solar energy into chemical fuel through photoelectrochemical (PEC) water
splitting. Herein, we report the development of a p-n heterojunction nanowire
(NW) based photoanode made of low cost earth-abundant materials. Densely-packed
and freestanding individual p-NiO/n-Fe2O3 heterojunction NWs are fabricated
through consecutive electrodeposition of Fe and Ni NWs inside the pores of the
anodic alumina template followed by controlled oxidation. Heterojunction
formation in individual NWs is confirmed through energy dispersive spectroscopy
(EDS) and transmission electron microscopy (TEM), along with elemental mapping on
individual NWs through electron energy loss spectroscopy (EELS). An inverted 'V'
shape nature of the Mott-Schottky curve suggests p-n diode like characteristics
of the heterojunction NWs. These p-n heterojunction NWs demonstrate a
significantly enhanced photocurrent density (~24 times at a potential of 1.23 V
vs. RHE) and a cathodic shift (~0.4 V) of the photocurrent onset potential
compared to the pristine Fe2O3 NW electrode, which can be attributed to the
synergistic combination of n-Fe2O3 with the co-catalyst p-NiO facilitating the
generation and transfer of photogenerated holes into the electrolyte for water
oxidation. This study validates the feasibility of developing Fe2O3 based
heterojunction photoelectrodes for efficient PEC water splitting.
PMID- 29963675
TI - Spin-coating-assisted fabrication of ultrathin physical hydrogel films with high
toughness and fast response.
AB - Hydrogel films have promising applications in medical dressings, flexible
electronics, etc. However, it is challenging to fabricate ultrathin hydrogel
films with high toughness and controllable thickness. Here, we report a facile
approach to prepare tough physical hydrogel films by spin-coating of a
poly(acrylic acid-co-acrylamide) (P(AAc-co-AAm)) solution and subsequent gelation
in FeCl3 solution to form carboxyl-Fe3+ coordination complexes. The thickness of
the obtained gel films, ranging from several to hundreds of micrometers, was
easily tunable by adjusting the spin conditions and polymer concentration. The
thus obtained hydrogel films showed excellent mechanical properties, with tensile
breaking strengths of 0.6-14.5 MPa, breaking strains of 140-840%, Young's moduli
of 0.1-61.7 MPa, and tearing fracture energies of 300-1300 J m-2. Based on this
approach, responsive tough hydrogel films can also be prepared by spin-coating of
a poly(acrylic acid-co-N-isopropylacrylamide) (P(AAc-co-NIPAm)) solution. The
obtained gel films showed a fast response (<60 s) and a large output force (~0.2
MPa) triggered by a concentrated saline solution, making them an ideal material
in the design of chemomechanical devices. Furthermore, a bilayer hydrogel film
was fabricated by two-step spin-coating of P(AAc-co-NIPAm) and P(AAc-co-AAm)
solutions, which showed reversible bending deformation under external stimuli.
This simple yet effective approach should be applicable to other systems to
prepare versatile hydrogel films with tunable thickness and promising
applications in diverse areas.
PMID- 29963676
TI - Imaging the magnetic structures of artificial quasicrystal magnets using resonant
coherent diffraction of circularly polarized X-rays.
AB - Unraveling nanoscale spin structures has long been an important activity
addressing various scientific interests, that are also readily adaptable to
technological applications. This has invigorated the development of versatile
nanoprobes suitable for imaging specimens under native conditions. Here we have
demonstrated the resonant coherent diffraction of an artificial quasicrystal
magnet with circularly polarized X-rays. The nanoscale magnetic structure was
revealed from X-ray speckle patterns by comparing with micromagnetic simulations,
as a step toward understanding the intricate relationship between the chemical
and spin structures in an aperiodic quasicrystal lattice. Femtosecond X-ray
pulses from free electron lasers are expected to immediately extend the current
work to nanoscale structure investigations of ultrafast spin dynamics, surpassing
the present spatio-temporal resolution.
PMID- 29963677
TI - Fluorescent boron complexes based on new N,O-chelates as promising candidates for
flow cytometry.
AB - This study presents the synthesis and optical properties of a new class of bright
green-yellow fluorescent dyes with potential applications in bioimaging. A facile
synthetic route via the chelation of aryl(hetaryl)aminoacryloylthiophene
scaffolds with a BF2 fragment is presented. The photophysical properties of the
dyes are attributed to the nature and position of electron-donating and electron
withdrawing substituents. Upon coordination to a BF2 fragment, characteristic
emission was observed, with lambdaem ranging from 503 to 543 nm and quantum
yields of 0.14-0.42. Compared with parent aryl(hetaryl)aminoacryloylthiophenes, a
significant red shift in absorption (up to 480 nm in solution) and emission (up
to 543 nm in solution and 610 nm in the solid state) and high chemical stability
and photostability were observed. The electron-accepting character of the
substituents on the terminal aromatic ring or replacing this fragment with
pyridine or pyrazine moieties resulted in increased quantum yields. To gain
insight into the electronic structures and optical properties, quantum mechanical
calculations were performed. The results of (TD-)DFT calculations supported the
structural and spectroscopic data and showed the features of electronic
distribution in the frontier molecular orbitals and active electrophilic and
nucleophilic sites in the compounds investigated. Synthesized BF2 complexes are
promising dyes for cell imaging and flow cytometry owing to their ready
penetration and accumulation in cells.
PMID- 29963679
TI - Improved structural design of single- and double-wall MnCo2O4 nanotube cathodes
for long-life Li-O2 batteries.
AB - Developing a cathode material with a stable pore structure and efficient
bifunctional activity toward oxygen electrochemistry is the key to achieve
practical and high-performance Li-O2 batteries. Here, hierarchically porous
MnCo2O4 nanotubes with single- or double-wall architecture are fabricated through
a facile electrospinning technique, by adjusting the concentration of the
electrospinning solution. The electrochemical measurements indicate that both
types of nanotubes possess excellent catalytic abilities toward oxygen reduction
and evolution reactions in alkaline aqueous or non-aqueous media. When used as
air-electrode catalysts for Li-O2 batteries, both single- and double-wall MnCo2O4
nanotubes show significantly improved electrochemical performance. In particular,
the novel double-wall MnCo2O4 nanotubes (DW-MCO-NT), with a high surface area and
a large pore volume almost twice as big as the single-wall nanotubes, can offer
numerous catalytically active sites as well as sufficient space to deposit
discharge products. The DW-MCO-NT based Li-O2 batteries can deliver a maximum
discharge capacity of 8100 mA h g-1, with a potential plateau at 2.77 V, and
achieve an excellent cyclability over 278 cycles, under strict conditions of 1000
mA h g-1 at 400 mA g-1 within 2.6-4.3 V. Moreover, the XRD and SEM analyses show
that the dominant discharge product with a particulate shape is crystal Li2O2 and
is prone to being completely decomposed, endowing the MnCo2O4 nanotube-based Li
O2 battery with a long cycle life.
PMID- 29963678
TI - Copper-catalyzed oxidative cross-dehydrogenative coupling of 2H-chromenes and
terminal alkynes.
AB - An efficient copper-catalyzed cross-dehydrogenative coupling of 2H-chromenes and
terminal alkynes mediated by DDQ has been established. A protic additive, EtOH,
proved to be crucial for harmonizing the oxidation with a subsequent alkynylation
step by retaining the oxidation state of an oxocarbenium ion in the form of
acetal. The CDC reaction exhibits a good substrate scope, with a range of
terminal aryl- and alkyl alkynes being well tolerated. The copper-catalyzed
alkynylation of 2H-chromene acetals with terminal alkynes was also explored.
PMID- 29963680
TI - Soluble Receptor for Advanced Glycation End Products: A Novel Biomarker for
Psoriasis Severity with Therapeutic Implications?
PMID- 29963681
TI - Successful Multidisciplinary Treatment of Chronic Facial Wounds in Junctional
Epidermolysis Bullosa.
PMID- 29963682
TI - Course and Predictors of Pruritus Following Burns: A Multilevel Analysis.
AB - Itch is a common problem after burns. Although the topic receives increasing
attention, the number of prospective studies is limited. The aim of this study
was to assess the influence of acute traumatic stress symptoms, controlled for
injury characteristics, age and sex, on itch over a period of 18 months using
multilevel analysis. A total of 226 respondents provided itch scores.
Participants completed the Burn Itch Questionnaire during admission (n = 208) and
at 3 (n =179), 12 (n =143) and 18 (n =99) months post-burn. They completed the
Impact of Event Scale to assess acute traumatic stress symptoms during admission.
Skin graft requirement, a higher level of acute traumatic stress symptoms and
younger age were statistically significant predictors of a higher itch score.
Younger age was particularly associated with higher itch scores during admission,
whereas the effect of skin grafting was particularly observed at 3 months post
burn. This study replicates the predictive role of traumatic stress symptoms,
which warrants further research.
PMID- 29963683
TI - Mortality in Patients with Bullous Pemphigoid: A Retrospective Cohort Study,
Systematic Review and Meta-analysis.
AB - There is little consensus regarding mortality data in bullous pemphigoid (BP).
The aim of this study was to evaluate mortality among a relatively large cohort
of Israeli patients with BP and to perform a meta-analysis synthesizing existing
data on 1-year mortality rates of patients with BP. This retrospective cohort
study of 287 patients diagnosed with BP between 2000 and 2015 compared the
mortality of patients with BP with age- and sex-matched control subjects in the
general population. The results showed 1-, 5- and 10-year mortality rates of
26.9%, 56.9% and 69.5%, respectively, and a 3.4-fold higher risk of death. A
systematic review and meta-analysis were then performed using a random effects
model. Including the current study, 25 studies comprising 4,594 patients met the
eligibility criteria. The pooled estimate of 1-year mortality rate was 23.5% (95%
confidence interval 20.2-26.8; I2=81%; p < 0.001). The pooled 1-year mortality
rate of European cohorts was prominently higher relative to the pooled rates of
cohorts from the USA and Asia.
PMID- 29963684
TI - Treatment of Actinic Keratosis with Photodynamic Therapy Using Red or Green
Light: A Comparative Study.
AB - Actinic keratosis (AK) is the most common in situ cancerous skin lesion. Compared
with other approved treatment modalities photodynamic therapy is preferred by
patients due to faster recovery and improved cosmetic outcome. However, pain
during irradiation is an important drawback. The aim of this study was to compare
the effectiveness and tolerability of topical aminolaevulinic acid-photodynamic
therapy in the treatment of AK on the head using red and green light. Complete
remissions after 3 sessions of photodynamic therapy at 2-week intervals following
9 months of observation were 91.67% for red light and 86.67% for green light
(difference not significant). The mean pain value was significantly greater in
areas irradiated with red light compared with green light for all 3 sessions.
This comparative study demonstrates that aminolaevulinic acid-photodynamic
therapy with green light is of similar efficacy as that with red light in the
treatment of middle/moderate AK, but causes less pain.
PMID- 29963685
TI - Genotype-Phenotype Correlations of Dystrophic Epidermolysis Bullosa in India:
Experience from a Tertiary Care Centre.
AB - Recent advances in the field of genomics have seen the successful implementation
of whole exome sequencing as a rapid and efficient diagnostic strategy in several
genodermatoses. The aim of this study was to explore the potential of molecular
studies in dystrophic epidermolysis bullosa (DEB) in India. Whole exome
sequencing was performed using genomic DNA from each case of epidermolysis
bullosa, followed by massively parallel sequencing. Resulting reads were mapped
to the human reference genome hg19. Sanger sequencing subsequently confirmed the
potentially pathogenic mutations. Whole exome sequencing of 18 patients with DEB
from 17 unrelated Indian families revealed 20 distinct sequence variants in the
COL7A1 gene including 2 widely prevalent mutations. Dominant inheritance was seen
in 7 patients, while 11 patients showed a highly variable recessive DEB. This
preliminary study using exome sequencing is clearly encouraging and will serve as
the basis for future large-scale molecular studies to actively identify and
understand DEB in the Indian population.
PMID- 29963686
TI - Antifibrinolytic therapy for preventing oral bleeding in people on anticoagulants
undergoing minor oral surgery or dental extractions.
AB - BACKGROUND: Individuals on continuous treatment with vitamin K antagonists (VKAs)
or direct oral anticoagulants (DOACs) are at increased risk of bleeding
complications during and after oral or dental procedures. Anticoagulant treatment
is preferably continued at the same dose, since dose reduction or discontinuation
of treatment is associated with an increased risk of thromboembolism. The use of
haemostatic measures during or after the procedure (or both) could enable
continuation of the oral anticoagulant treatment. OBJECTIVES: We aimed to assess
the efficacy of antifibrinolytic agents for preventing bleeding complications in
people on oral anticoagulants undergoing minor oral surgery or dental
extractions. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic
Disorders Coagulopathies Trials Register, compiled from electronic database
searches and handsearching of journals and conference abstract books. We also
searched the reference lists of relevant articles and reviews. We searched
PubMed, Embase and the Cochrane Library. Additional searches were performed using
ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP),
the CINAHL database of nursing and allied health services, the open access
ProQuest dissertation database, papers and reports from the American College of
Clinical Pharmacy (ACCP) and abstract books from annual scientific
conferences.Date of last search: 04 January 2018. SELECTION CRITERIA: Randomised
and quasi-randomised controlled trials in people on continuous treatment with
VKAs or DOACs undergoing oral or dental procedures using antifibrinolytic agents
(tranexamic acid (TXA) or epsilon aminocaproic acid) to prevent perioperative
bleeding compared to no intervention or usual care with or without placebo. DATA
COLLECTION AND ANALYSIS: Two authors independently screened the titles and
abstracts of all identified articles. Full texts were obtained from potentially
relevant abstracts and two authors independently assessed these for inclusion
based of the selection criteria. A third author verified trial eligibility. Two
authors independently performed data extraction and risk of bias assessments
using standardized forms. The quality of the evidence was assessed using GRADE.
MAIN RESULTS: No eligible trials in people on continuous treatment with DOACs
undergoing oral or dental procedures were identified.Three randomised trials and
one quasi-randomised trial (follow-up in all was seven days) in people on
continuous treatment with VKAs were included with a total of 253 participants
(mean age 60 years). Two trials published in 1989 and 1993 compared the
antifibrinolytic agent TXA with placebo in people using VKAs. Two other trials
were published in 1999 and 2015 and compared TXA with gelatin sponge and sutures,
and dry gauze compression, respectively. In all included trials, those who were
treated with VKAs had international normalised ratio (INR) values within the
therapeutic range and TXA was applied locally, not systemically.The two trials
from 1989 and 1993 comparing TXA with placebo showed a statistically significant
beneficial effect regarding the number of major postoperative bleeding episodes
requiring intervention, with a pooled risk difference (RD) of -0.25 (95%
confidence interval (CI) -0.36 to -0.14) (128 participants) (moderate-quality
evidence). For the two trials that compared TXA with either gelatin sponge and
sutures or with dry gauze compression, there was no difference between the TXA
and the standard care group, RD 0.02 (95% CI -0.07 to 0.11) (125 participants)
(moderate-quality evidence). The combined RD of all included trials was -0.13
(95% CI -0.30 to 0.05) (moderate-quality evidence). There were no side effects of
antifibrinolytic therapy that required treatment withdrawal (128 participants)
(moderate-quality evidence). Despite heterogeneity between trials with respect to
the different haemostatic measures used in the control groups, the trials were
comparable regarding design and baseline participant characteristics.Overall, we
considered the risk of bias to be low in the trials comparing TXA with placebo
and moderate in the trials comparing TXA with alternative haemostatic measures.
AUTHORS' CONCLUSIONS: Based on the results of this Cochrane Review, there seems
to be a beneficial effect of locally applied TXA in preventing oral bleeding in
people on continuous treatment with VKAs undergoing minor oral surgery or dental
extractions. However, the small number of identified randomised controlled
trials, the relatively small number of participants included in the trials and
the differences in standard therapy and treatment regimens between trials, do not
allow us to conclude definite efficacy of antifibrinolytic therapy in this
population.We were unable to identify any eligible trials in people on continuous
treatment with DOACs undergoing oral or dental procedures. Therefore, a
beneficial effect of antifibrinolytic therapy can currently only be assumed based
on data from the people using VKAs.
PMID- 29963687
TI - Prospective study: Long-term outcome at 12-15 years after aneurysmal subarachnoid
hemorrhage.
AB - BACKGROUND: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have poor
outcome. Studies on outcome beyond 1 year post-aSAH are few, and late recovery is
poorly investigated, initiating this prospective outcome study on patients 12-15
years after an aSAH. We hypothesized to find; functional improvement > 1 year
post-ictus; increased long-term mortality in aSAH patients vs matched controls,
and finally to present; predictors of long-term favorable outcome (GOS 4-5).
METHODS: We prospectively investigated patients, admitted 2000-2003 to the
Sahlgrenska University Hospital, 1 year post-ictus using Glasgow Outcome Scale
(GOS). The patients were revalidated 12-15 years post-aSAH by structured
telephone interviews (GOS), followed by statistical analysis. RESULTS: A total of
158 patients were included, (women n = 114, men n = 44), with a mean age of 55
years at aSAH. Patients treated with surgical clipping had lower mortality. At
the follow-up 12-15 years post-aSAH, all 103 survivors (65.2%) were categorized
as having; good recovery (39.9%), moderate disability (15.2%), or severe
disability (10.1%). Within the patient cohort, 23.6% improved GOS over time.
Fifty-five patients died, median at 4 years post-ictus. aSAH patients had 3.5
times increased mortality 12-15 years post-ictus vs matched controls (P < .0001).
Patients with favorable outcome at 1 year (67.3%, n = 101) had similar survival
probability as control patients. Prognostic indicators of long-term favorable
outcome were low age and high GOS at 1-year follow-up, (AUCROC, 0.79).
CONCLUSIONS: Individual functional improvement was found >1 year post-ictus.
Patients with favorable outcome at 1 year had similar long-term life expectancy
as the general population. Indicators of long-term favorable prognosis were low
age at ictus and high GOS at 1-year follow-up.
PMID- 29963688
TI - Strength in Numbers: A National Monthly Case Conference Series for Fellows.
AB - Small fellowship programs face challenges in providing learners with sufficiently
diverse experiences and patient populations. The Fellows Most Difficult Case
Conference is designed to broaden geriatric medicine fellows' exposure to cases
and to faculty and fellows from around the country through a monthly telephone
conference. We describe this innovative approach to a national monthly complex
case conference that fellows from almost one-third of geriatrics fellowship
programs attend, including its value to geriatric fellows and faculty and
administrative costs. Once per month, a fellow presents a case, a moderator leads
the discussion, and 2 faculty members provide teaching points during the 60
minute session. Participants rated the conference's value using an 11-item on
line survey followed by a debriefing held during a regularly scheduled 2017
monthly conference. Thirty-six percent of eligible participants responded to the
survey (67/186), with 75% of respondents reporting that they applied knowledge
gained from the conferences to their patient care at least 1 or 2 times per month
and 41% that they applied it at least once per week. Participants appreciated the
inclusion of multiple programs, the duration of the conference, and the
interactive approach. Our administration time was less than 5 hours per month,
plus a few additional hours annually to create the academic year schedule. We
believe that this national case conference, the first of its kind in the country,
involving almost one-third of geriatrics fellowship programs, is an innovative
and valuable way for fellows to explore complex cases and variations in regional
perspectives and to connect with additional colleagues.
PMID- 29963689
TI - Accuracy of POSSUM and Nottingham Hip Fracture Score.
PMID- 29963690
TI - Response to the letter by Dr. Forster and Pitkanen regarding our manuscript
"Incidence and related factors for intraoperative failed spinal anaesthesia for
lower limb arthroplasty".
PMID- 29963691
TI - Organized physical activity programs: improving motor and non-motor symptoms in
neurodevelopmental disorders.
PMID- 29963692
TI - Dying of Thirst in Palliative Care.
PMID- 29963693
TI - Transorbital ultrasonography for measuring optic nerve atrophy in multiple
sclerosis.
AB - OBJECTIVE: we aimed to evaluate the utility of transorbital ultrasonography (TOS)
in optic nerve assessment and quantification of ON atrophy in MS patients, and to
determine whether ON atrophy correlates with the disease duration and disability
measured on the Kurtzke Expanded Disability Status Scale (EDSS). MATERIALS AND
METHODS: Prospective, multicentre, blinded cohort study of 59 patients diagnosed
with relapsing-remitting MS and 36 controls. RESULTS: When measured with TOS, the
diameter of both the right (2.69 +/- 0.30 mm in cases; 3.20 +/- 0.19 mm in
controls, P < .0001) and left (2.71 +/- 0.26 mm in cases; 3.24 +/- 0.15 mm
controls, P < .0001) ON of study patients was smaller than controls. We observed
a negative correlation between EDSS and both right (rho = .524) and left (rho =
.469) ON diameter. We also observed a negative correlation between disease
duration and both right (r = .602) and left (r = .538) ON diameter. No difference
was observed in the diameter of both ON among patients with a history of optic
neuritis (right OND 2.68 +/- 0.29 mm; left OND 2.69 +/- 0.25 mm) and patients
with no history of optic neuritis (right OND 2.70 +/- 0.30 mm; left OND 2.73 +/-
0.27 mm) (P = .805; P = .651). CONCLUSIONS: The thickness of ON measured with TOS
is correlated with EDSS and the duration of the disease without being interfered
by the previous history of optic neuritis. TOS could be a reliable technique for
measuring ON atrophy in MS.
PMID- 29963694
TI - Haematocrit and plasma volume during induction of anaesthesia.
PMID- 29963695
TI - Reply to: Dying of Thirst in Palliative Care.
PMID- 29963696
TI - Prevalence of Morbidity at Extreme Old Age in Germany: An Observational Study
Using Health Claims Data.
AB - We assessed the prevalence of morbidity in long-lived individuals according to
age and age at death and explored the association between dementia and other
diseases and surviving to age 90 and 100. Using health claims data from the
largest German health insurer from 2004 to 2013, we followed birth cohorts from
1908 to 1913 from age 95 until death or survival to age 100 (n=2,865) and
compared them with birth cohorts from 1918 to 1923 and their survival from age 85
to age 90 (n=17,013). We observed their exact date of death and main categories
of morbidity based on International Classification of Diseases, Tenth Revision,
diagnoses. For all diseases studied, when differentiated according to age at
death, prevalence continued to increase with age. Nonagenarians and centenarians
had significantly lower disease prevalence at each age. Dementia was associated
with the highest risk of dying before becoming a centenarian (hazard ratio
(HR)=1.63, 95% confidence interval (CI)=1.50-1.78), followed closely by the
residual category other chronic heart disease (HR=1.42, 95% CI=1.30-1.56).
Results were even stronger for the younger cohort. Our study shows that
exceptionally long-lived individuals are different in terms of good health.
Survival at these high ages depends primarily on the absence of dementia and
chronic heart disease, with acute heart disease and pneumonia playing important
roles as diseases leading directly to death.
PMID- 29963697
TI - Stroke in childhood neurofibromatosis type 2.
PMID- 29963698
TI - The making of an egalitarian elite: school ethos and the production of privilege.
AB - Research on privilege and education often focuses on institutions that are elite
in a rather traditional way, for example schools that instruct the children of
the upper classes according to a reproductive logic that reinforces existing
inequalities. The present article addresses the fostering of advantage from the
angle of a more ambiguous case. The Global College, a municipal Swedish upper
secondary school specialized in environmental issues and global justice, offers
an empirical prism for discussing the cultivation of elite identification through
the formative potential of an egalitarian ethos. The relation between ethics and
class is examined, not only in terms of how moral stands are classed, but also by
investigating into the productive capacities of such orientation. Through
extensive ethnographic fieldwork, the study unfolds how a possible tension
between egalitarianism and elitism resolves into a productive relation whereby
the students' incarnation of ethico-political ideals becomes a means for
developing agency, confidence, entrepreneurial skills and an overall sense of
ease.
PMID- 29963699
TI - Detection of gaps between high-intensity focused ultrasound (HIFU)-induced
lesions using transient axial shear strain elastograms.
AB - PURPOSE: High-intensity focused ultrasound (HIFU) is becoming an effective and
noninvasive treatment modality for cancer and solid tumors. In order to avoid the
cancer relapse and guarantee the success of ablation, there should be no gaps
left among all HIFU-generated lesions. However, there are few imaging approaches
available for detecting the HIFU lesion gaps in real time during ablation.
METHODS: Transient axial shear strain elastograms (ASSEs) were proposed and
evaluated both numerically and experimentally to detect the lesion gaps
immediately after the cessation of therapeutic HIFU exposure. Acoustic intensity
and subsequent acoustic radiation force were first calculated by solving the
nonlinear Khokhlov-Zabolotskaya-Kuznetzov (KZK) equation. Motion of being- and
already-treated lesions during and after HIFU exposure was simulated using the
transient dynamic analysis module of finite element method (FEM). The
corresponding B-mode sonography of tissue-mimicking phantom with two HIFU lesions
inside was simulated by FIELD II, and then axial strain elastograms (ASEs) under
static compression and transient ASSEs were reconstructed. An ultrasound imaging
probe was integrated with the HIFU transducer and used to obtain radio frequency
(RF) echo signals at high frame rate using plane wave imaging (PWI). The
resulting strains were mapped using the correlation-based method and block search
strategy. RESULTS: Acoustic radiation force from the therapeutic HIFU burst is
sufficiently strong to produce significant displacement. As a result, large and
highly localized axial shear strain appears in the gap zone between two HIFU
generated lesions and then disappears after sufficient HIFU ablation (no gap
between them). Such capability of detecting the lesion gap is validated at the
varied acoustic radiation force density, gap width, and the size of the lesion.
In contrast, conventional ASEs using the static compression cannot distinguish
whether a gap exists between lesions. Static ASEs and transient ASSEs
reconstructed using both high-speed photography and sonography in the gel phantom
show the same conclusion as that in the simulation. Ex vivo tissue experiments
further confirmed that the presence of large axial shear strain in the gap zone.
The ratios of axial shear strain in the porcine kidney and liver samples had
statistical differences for two HIFU-generated lesions without and with a gap (P
< 0.05). CONCLUSIONS: Large axial shear strain induced by the acoustic radiation
force from therapeutic HIFU burst only appears between two HIFU-generated lesions
with a gap between them. Transient ASSEs reconstructed immediately after the
cession of HIFU exposure can easily, reliably, and sensitively detect the gap
between produced lesions, which would provide real-time feedback to enhance the
success of HIFU ablation.
PMID- 29963700
TI - Children's and Parents' Well-Being in Joint Physical Custody: A Literature
Review.
AB - Joint physical custody (JPC), a parental care arrangement in which a child lives
with each parent for at least 25-50% of the time after separation or divorce, is
increasingly common in many Western societies. This is a major shift from the
standard of sole physical custody, with mostly mothers providing primary
childcare after a parental separation or divorce. The increasing share of
separated or divorced parents who practice JPC, which in some countries, US
states, and regions reaches 30% and more, results from increasing gender equality
due to mothers participating considerably in the labor force and fathers being
actively involved in their children's daily lives. This review focuses on the
effects of JPC on children's and parents' well-being, based on 40 studies from
North America, Australia, and Europe published between 2007 and 2018. In sum,
there is empirical evidence from different countries that suggests that JPC
arrangements can have positive effects on the well-being of children and of
parents. However, the existing studies are conceptually, methodologically, and
contextually very heterogeneous. In addition, self-selected highly educated
parents with a high socio-economic status, a low conflict level, and children
between the ages of 6-15 practicing JPC dominate the samples. Thus, the risks and
benefits of JPC are not clear yet and are heavily debated by advocates and
academics. The review concludes with suggestions for future research.
PMID- 29963701
TI - Comparing square root method of measuring the cardiac output by means of aortic
impedance change component to Kubicek's method.
AB - PURPOSE: The aim of this study is to explore a calculated method used to measure
the cardiac output using the aortic impedance change component of reconstructed
impedance cardiography. METHODS: Routine impedance cardiography was measured
using Kubicek's method with four ring electrodes. The thoracic mixed impedance
changes were measured by six leads, which consisted of 15 electrodes. The aortic
impedance change component was separated from six thoracic mixed impedance
changes through waveform reconstruction. The square root formula used to
calculate the cardiac output was deduced based on the thoracic impedance change
equation and the aortic volume change hypothesis during the systole period. The
cardiac outputs of 180 normal adults and 72 patients with cardiac insufficiency
who could still walk freely were contrastively computed with both Kubicek's
formula and the square root formula. RESULTS: For 180 normal adults, the cardiac
index (CI) computed with the square root formula was 3.60 +/- 0.45 L/min/m2 ,
with normal values ranging from 2.7 to 4.5 L/min/m2 . A total of 163 cases
(90.6%) had a CI in the standard range (2.7-4.3 L/min/m2 ) adopted in clinical
applications. The CI computed with Kubicek's formula was 3.61 +/- 0.86 L/min/m2 ,
with normal values ranging from 1.9 to 5.3 L/min/m2 , and only 115 cases (63.9%)
had a CI in the above standard range. Among the 72 patients with cardiac
insufficiency, 20 (27.8%) patients had a CI < 2.0 L/min/m2 with Kubicek's
formula. Of these 20 cases, 9 cases had a CI < 1.5 L/min/m2 , and 4 cases had a
CI < 1.1 L/min/m2 . In contrast, none of the 72 patients had a CI < 2.0 L/min/m2
with the square root formula. In addition, the influence of the chest
circumference on the CI was lower for the square root formula than for Kubicek's
formula. CONCLUSIONS: The CI calculated with the square root formula had a better
normal value range, was more accurate for the patients with cardiac
insufficiency, and was less affected by the chest circumference than the CI
calculated with Kubicek's formula.
PMID- 29963702
TI - Technical Note: Emission expectation maximization look-alike algorithms for x-ray
CT and other applications.
AB - PURPOSE: In emission tomography, the expectation maximization (EM) algorithm is
easy to use with only one parameter to adjust - the number of iterations. On the
other hand, the EM algorithms for transmission tomography are not so user
friendly and have many problems. This paper develops a new transmission algorithm
similar to the emission EM algorithm. METHODS: This paper develops a family of
emission-EM-look-alike algorithms by expressing the emission EM algorithm in the
additive form and changing the weighting factor. One of the family members can be
applied to transmission tomography such as the x-ray computed tomography (CT).
RESULTS: Computer simulations are performed and compared with a similar algorithm
by a different group using the transmission CT noise model. Our algorithm has the
same convergence rate as theirs, and our algorithm provides better contrast-to
noise ratio for lesion detection. CONCLUSIONS: For any noise variance function,
an emission-EM-look-alike algorithm can be derived. This algorithm preserves many
properties of the emission EM algorithm such as multiplicative update, non
negativity, faster convergence rate for the bright objects, and ease of
implementation.
PMID- 29963703
TI - Ecological genomics of variation in bud-break phenology and mechanisms of
response to climate warming in Populus trichocarpa.
AB - Spring bud-break phenology is a critical adaptive feature common to temperate
perennial woody plants. Understanding the molecular underpinnings of variation in
bud-break is important for elucidating adaptive evolution and predicting outcomes
relating to climate change. Field and controlled growth chamber tests were used
to assess population-wide patterns in bud-break from wild-sourced black
cottonwood (Populus trichocarpa) genotypes. We conducted a genome-wide
association study (GWAS) with single nucleotide polymorphisms (SNPs) derived from
whole genome sequencing to test for loci underlying variation in bud-break. Bud
break had a quadratic relationship with latitude, where southern- and northern
most provenances generally broke bud earlier than those from central parts of the
species' range. Reduced winter chilling increased population-wide variation in
bud-break, whereas greater chilling decreased variation. GWAS uncovered 16 loci
associated with bud-break. Phenotypic changes connected with allelic variation
were replicated in an independent set of P. trichocarpa trees. Despite phenotypic
similarities, genetic profiles between southern- and northern-most genotypes were
dissimilar based on our GWAS-identified SNPs. We propose that the GWAS-identified
loci underpin the geographical pattern in P. trichocarpa and that variation in
bud-break reflects different selection for winter chilling and heat sum
accumulation, both of which can be affected by climate warming.
PMID- 29963705
TI - Dentomaxillofacial radiology in Australia and dentist satisfaction with radiology
reports.
AB - BACKGROUND: Dentomaxillofacial Radiology (DMFR) is comprised of the smallest
cohort of specialists in Australia. A survey was undertaken to assess awareness
of DMFR, radiology reporting and referring protocols as well as dental
practitioners' satisfaction with their radiology reporting arrangements. METHODS:
An original online survey created using Checkbox? was sent to dental
practitioners. The survey was promoted on Australian-based dental Facebook forums
and emailed to targeted members via Australian professional dental associations.
RESULTS: A total of 399 responses were received, with over 80% of respondents
aware of DMFR as a specialty. Approximately 40% of practitioners were self
reporting their imaging. There was correlation between increased satisfaction
with external reporting and utilization of DMFR services and decreased
satisfaction with medical radiology services. More than 90% of general dentists
and greater than 85% of dental specialists prefer DMFR reports to medical
radiology reports. Approximately 80% of practitioners believed that their
satisfaction would change positively if they had access to a DMFR report.
CONCLUSION: The research indicates a high degree of self-reporting or non
reporting by dental practitioners. There is low satisfaction with external
reporting performed by Medical Radiologists primarily due to a lack of dental
knowledge or detail and a preference for DMF Radiology reports.
PMID- 29963704
TI - Macrophage targeting: opening new possibilities for cancer immunotherapy.
AB - Tumour-infiltrating immune cells regulate tumour development and progression
either negatively or positively. For example, cytotoxic lymphocytes (CTL) such as
CD8+ T and natural killer (NK) cells can recognize and eliminate cancer cells,
and thereby restrict the tumour growth and metastasis, if they exert full
cytotoxicity. In contrast, tumour-infiltrating myeloid cells such as tumour
associated macrophages (TAM) promote the expansion and dissemination of cancer
cells depending on their functional states. Given the tumour-killing ability of
CTL, the augmentation of CTL-induced antitumour immune reactions has been
considered as an attractive therapeutic modality for lethal solid tumours and
several promising strategies have emerged, which include immune checkpoint
inhibitors, cancer vaccines and adoptive CTL transfer. These immunotherapies are
now tested in clinical trials and have shown significant antitumour effects in
patients with lymphoma and some solid tumours such as melanoma and lung cancer.
Despite these encouraging results, these therapies are not efficient in a certain
fraction of patients and tumour types with tumour cell-intrinsic mechanisms such
as impaired antigen presentation and/or tumour cell-extrinsic mechanisms
including the accumulation of immunosuppressive cells. Several animal studies
suggest that tumour-infiltrating myeloid cells, especially TAM, are one of the
key targets to improve the efficacy of immunotherapies as these cells can
suppress the functions of CD8+ T and NK cells. In this review, we will summarize
recent animal studies regarding the involvement of TAM in the immune checkpoint,
cancer vaccination and adoptive CTL transfer therapies, and discuss the
therapeutic potential of TAM targeting to improve the immunotherapies.
PMID- 29963706
TI - Continuous vital sign monitoring after major abdominal surgery-Quantification of
micro events.
AB - INTRODUCTION: Millions of patients undergo major abdominal surgery worldwide each
year, and the post-operative phase carries a high risk of respiratory and
circulatory complications. Standard ward observation of patients includes vital
sign registration at regular intervals. Patients may deteriorate between
measurements, and this may be detected by continuous monitoring. The aim of this
study was to compare the number of micro events detected by continuous monitoring
to those documented by the widely used standardized Early Warning Score (EWS).
METHODS: Fifty patients were continuously monitored with peripheral arterial
oxygen saturation (SpO2 ), heart rate (HR), and respiratory rate (RR) the first 4
days after major abdominal cancer surgery. EWS was monitored as routine practice.
Number and duration of events were analyzed using Fisher's exact test and
Wilcoxon rank sum test. RESULTS: Continuous monitoring detected a SpO2 <92% in
98% of patients vs 16% of patients detected by EWS (P < .0001). Micro events of
SpO2 <92% lasting longer than 60 minutes were found in 58% of patients by
continuous monitoring vs 16% by the EWS (P < .0001). Fifty-two percent of
patients had micro events of SpO2 <85% lasting longer than 10 minutes. Continuous
monitoring found tachycardia in 60% of patients vs 6% by the EWS. Frequency of
events for bradycardia, tachypnea, and bradypnea showed similar patterns.
CONCLUSION: Very low SpO2 and tachycardia in post-operative patients are common
and under-diagnosed by the EWS. Continuous monitoring can discover these micro
events and potentially contribute to earlier detection and, potentially, result
in prevention of clinical complications.
PMID- 29963707
TI - Influence of tooth location on coronally advanced flap procedures for root
coverage.
AB - BACKGROUND: The efficacy of Coronally Advance Flap (CAF) has been extensively
evaluated and several parameters influencing the results, such as interproximal
attachment loss, recession defect size, papilla dimension, flap thickness, have
also been identified. However, the influence of tooth location has not been
systematically investigated yet. Therefore, the aim of this systematic review was
to evaluate the influence of tooth location on the outcomes of CAF. METHODS: A
literature search on PubMed, EMBASE, Cochrane libraries and hand-searched journal
until September 2017 was performed to identify clinical studies reporting the
outcome of CAF for localized gingival recessions (GRs) for each single tooth.
RESULTS: Eighteen articles reporting 399 localized GRs treated with CAF were
included in the present systematic review. Canines and incisors were related to a
higher mRC and CRC than premolars and molars (odds ratio 1.63) (p < 0.05), while
the right side showed a higher CRC than the left side (odds ratio 1.60) (p <
0.05). No differences were found between maxillary and mandibular dentition (p >
0.05). The addition of a graft such as Connective Tissue Graft (CTG) with or
without Enamel Matrix Derivative (EMD) was shown to enhance the outcomes compared
to CAF alone (p < 0.05). CRC was negatively affected by initial clinical
attachment level (p < 0.05), but not from the initial recession depth (p > 0.05).
CONCLUSIONS: Tooth location plays an important role on mRC and CRC following CAF.
The addition of CTG or substitutes, especially with biological agents (EMD),
enhance the clinical outcomes compared to CAF alone.
PMID- 29963708
TI - Elementary school children's associations of antisocial behaviour with risk
taking across 7-11 years.
AB - BACKGROUND: The impact of childhood antisocial behaviour on future maladaptation
has been acknowledged. Risk-taking has been associated with antisocial behaviour
in adolescents and adults, but its association with childhood antisocial
behaviour is understudied. In this study, we explored the association of
children's risk-taking with antisocial behaviour in mainstream elementary
schoolchildren studied longitudinally across 7-11 years. METHODS: One thousand
and eighty-six children (51% boys) were assessed in three annual waves.
Antisocial behaviours (aggressive, covert antisocial and oppositional defiant
behaviour) were assessed using teacher- and peer-reports. Risk-taking was
measured using the Balloon Analogue Risk Task (BART). The association of
antisocial behaviour with risk-taking was analysed using parallel growth models.
RESULTS: Children with higher levels of risk-taking at age 7 showed increased
growth in peer-reported aggression from age 7 to 11. Risk-taking, that is
increased levels at age 7 in boys and increased growth in girls, predicted
increased growth in peer-reported oppositional defiant behaviour. Associations of
risk-taking with teacher-reported aggression and covert antisocial behaviour were
at trend level. CONCLUSIONS: Results indicated that already in childhood, among
typically developing children, risk-taking is associated with the development of
antisocial behaviour. Future research focused on antisocial behaviour, but also
school mental health workers and clinicians should take into account that already
in childhood, risk-taking might affect antisocial behaviour development.
PMID- 29963709
TI - Early developmental pathways to childhood symptoms of attention-deficit
hyperactivity disorder, anxiety and autism spectrum disorder.
AB - BACKGROUND: Children with autism spectrum disorder (ASD) often have co-occurring
symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is
unclear whether these disorders arise from shared or distinct developmental
pathways. We explored this question by testing the specificity of early-life
(infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms
compared to ASD symptoms. METHODS: Infants (n = 104) at high and low familial
risk for ASD took part in research assessments at 7, 14, 24 and 38 months, and 7
years of age. Symptoms of ASD, ADHD and anxiety were measured by parent report at
age 7. Activity levels and inhibitory control, also measured by parent report, in
infancy and toddlerhood were used as early-life predictors of ADHD symptoms.
Fearfulness and shyness measured in infancy and toddlerhood were used as early
life predictors of anxiety symptoms. Correlations and path analysis models tested
associations between early-life predictors and mid-childhood ADHD and anxiety
symptoms compared to mid-childhood ASD symptoms, and the influence of controlling
for ASD symptoms on those associations. RESULTS: Increased activity levels and
poor inhibitory control were correlated with ADHD symptoms and not ASD or
anxiety; these associations were unchanged in path models controlling for risk
group and ASD symptoms. Increased fearfulness and shyness were correlated with
anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path
analysis, the association between shyness and anxiety became nonsignificant, and
when further controlling for ASD symptoms the association between fearfulness and
anxiety became marginal. CONCLUSIONS: The specificity of early-life predictors to
ADHD symptoms suggests early developmental pathways to ADHD might be distinct
from ASD. The overlap in early-life predictors of anxiety and ASD suggests that
these disorders are difficult to differentiate early in life, which could reflect
the presence of common developmental pathways or convergence in early behavioural
manifestations of these disorders.
PMID- 29963710
TI - Linker histone H1FOO regulates the chromatin structure in mouse zygotes.
AB - The chromatin structure in one-cell-stage mouse embryos is extremely loose and
becomes tighter at the two-cell stage. As linker histones are involved in higher
order chromatin structure, we examined the involvement of the linker histone
variant H1foo in the change of chromatin looseness between the one- and two-cell
stages. H1foo knockdown causes the chromatin structure to be tighter in the
pronucleus and increases deposition of the histone H3 variant H3.1/3.2 in the
peripheral region of the pronucleus in one-cell-stage embryos. The decrease in
chromatin looseness at the two-cell stage is less after overexpressing H1foo.
These results suggest that H1foo is involved in the change in chromatin structure
via nuclear deposition of H3 variants between the one- and two-cell stages.
PMID- 29963711
TI - Differentiating typical from atypical perpetration of sibling-directed aggression
during the preschool years.
AB - BACKGROUND: Sibling aggression is common and often viewed as benign. Although
sibling aggression can be harmful for the victims, it may also be a marker of
clinical risk for the aggressor. We differentiated typical from atypical levels
of perpetration of sibling-directed aggression among preschoolers, a
developmental period in which aggression is a normative misbehavior, by (a)
identifying how frequently aggressive behaviors targeted at a sibling must occur
to be psychometrically atypical; (b) mapping the dimensional spectrum of sibling
directed aggression from typical, more commonly occurring behaviors to rarer,
more atypical, actions; and (c) comparing the psychometric atypicality and
typical-to-atypical spectrum of sibling-directed aggression and peer-directed
aggression. METHODS: Parents (N = 1,524) of 3- (39.2%), 4-(36.7%), and 5-(24.1%)
year-olds (51.9% girls, 41.1% African-American, 31.9% Hispanic; 44.0% below the
federal poverty line) completed the MAP-DB, which assesses how often children
engage in aggressive behaviors. We used item-response theory (IRT) to address our
objectives. RESULTS: Most aggressive behaviors toward siblings were
psychometrically atypical when they occurred 'most days' or more; in contrast,
most behaviors targeted at peers were atypical when they occurred 'some days' or
more. With siblings, relational aggression was more atypical than verbal
aggression, whereas with peers, both relational and physical aggression were more
atypical than verbal aggression. In both relationships, the most typical behavior
was a verbally aggressive action. Results were broadly replicated in a second,
independent sample. CONCLUSIONS: These findings are a first step toward
specifying features of sibling aggression that are markers of clinical risk and
belie the notion that sibling aggression is inherently normative.
PMID- 29963712
TI - Long-term survival of a patient with neurofibromatosis type 1 diagnosed with
multiple malignant peripheral nerve sheath tumors.
PMID- 29963713
TI - A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic
hepatitis B.
AB - BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B
(CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)
identified polymorphism in the STAT4 gene that contributes to the risk for
hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum
of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional
mechanisms for this effect are unknown and the role of the variant in modulating
HBV disease in Caucasians has not been investigated. AIMS: To determine whether
STAT4 genetic variation is associated with liver injury in Caucasian patients
with CHB and to investigate potential mechanisms mediating this effect. METHODS:
STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy
controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation
and secretion of interferon-gamma (IFN-gamma) according to STAT4 genetic
variation was examined. RESULTS: STAT4 rs7574865 genotype was independently
associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and
advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele
frequency of rs7574865 was significantly lower than that in healthy controls.
rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in
NK cells, while NK cells from patients with the risk genotype had impaired STAT4
phosphorylation following stimulation with IL-12/IL-18 and a reduction in
secretion of IFN-gamma. CONCLUSION: Genetic susceptibility to HBV persistence,
hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865
variant. Downstream effects on NK cell function through STAT4 phosphorylation
dependent IFN-gamma production likely contribute to these effects.
PMID- 29963714
TI - Differences in semen characteristics between patients with testicular cancer and
other malignancies using various cut-off values.
AB - OBJECTIVES: To compare semen parameters between patients with testicular cancer
and other malignancies using various cut-off values, and to evaluate the
correlation between semen parameters and intracytoplasmic sperm injection
outcomes. METHODS: We retrospectively investigated semen parameters before cancer
treatment in 117 patients with malignancies who cryopreserved sperm at Hirosaki
University Hospital between November 1999 and May 2016. We compared semen
parameters between patients with testicular cancer and other malignancies (non
testicular cancer), seminoma and non-seminoma, and stage I testicular cancer and
stage II/III testicular cancer. The assessment of cut-off values recommended by
the World Health Organization and the total motile sperm count was carried out
between the testicular cancer and non-testicular cancer groups. The
intracytoplasmic sperm injection outcomes in those using preserved sperm were
assessed. RESULTS: Of the 111 patients enrolled, 29 (26%) had testicular cancer
and 82 (74%) had non-testicular cancer. Patients with testicular cancer showed
significantly lower total sperm concentration than non-testicular cancer
patients. The cut-off value of total sperm concentration distinguished the
patient proportions exceeding the cut-off between patients with testicular cancer
(41%) and non-testicular cancer (66%). The comparison between patients with
seminoma versus non-seminoma and stage I versus stage II/III testicular cancer
presented no significant differences in semen parameters. No correlation between
pretreatment semen parameters and intracytoplasmic sperm injection outcomes was
observed. CONCLUSIONS: Although testicular cancer patients show lower total sperm
concentration, intracytoplasmic sperm injection outcomes are acceptable. Further
studies on the fertility potential of testicular cancer patients are warranted.
PMID- 29963715
TI - Impacts of temperature, morpholine, and chronic radiation on the embryonic
development of round whitefish (Prosopium cylindraceum).
AB - During incubation, round whitefish embryos may experience fluctuating or elevated
temperatures from natural (e.g., seasonal temperature changes) and/or
anthropogenic sources. Anthropogenic sources like once-through cooling discharges
from nuclear power plants can also expose embryos to chemicals (e.g., morpholine)
and/or radiation. To examine the effects of these potential stressors on
embryogenesis, round whitefish were incubated under fluctuating or constant
temperatures, with morpholine or 137 Cs gamma rays. We report the percentage of
prehatch and posthatch mortality, developmental rate, hatch dynamics, and
morphometrics at 4 development stages. Embryos reared at constant temperatures
had delayed developmental stage onset and median hatch, higher mortality at
constant 8 degrees C, and lower mortality at <=5 degrees C, compared with
embryos reared under seasonal temperature regimes. Embryos incubated with >=500
mg L-1 morpholine (>200* regulatory limits) had advanced hatch, reduced body
size, and increased prehatch (100% at 1000 mg L-1 ) and posthatch (~95% at 500 mg
L-1 ) mortality compared with controls. Relative to controls, embryos irradiated
with >=0.16 mGy/d had larger body mass early in development, and all irradiated
embryos had decreased posthatch mortality; the lowest dose was >300* discharge
limits. Our study suggests that fluctuating or elevated temperatures and high
dose morpholine can alter development rate, hatch dynamics, and growth, and/or
increase mortality compared with embryos reared at constant temperatures of <=5
degrees C; conversely, low-dose irradiation had transient developmental effects
but may benefit early posthatch survival. Environ Toxicol Chem 2018;37:2593-2608.
(c) 2018 SETAC.
PMID- 29963716
TI - Lichen myxedematosus associated with monoclonal gammopathy of undetermined
significance: A case report and a review of Japanese patients.
PMID- 29963717
TI - Incidence of Stevens-Johnson syndrome following combination drug use of
allopurinol, carbamazepine and phenytoin in Taiwan: A case-control study.
AB - The goal of our study was to investigate the incidence of Stevens-Johnson
syndrome (SJS), the frequency of SJS diagnosis, and the association between SJS
and prior use of allopurinol, carbamazepine or phenytoin. This case-control study
utilized data from the National Health Insurance Research Database (NHIRD) of
Taiwan. Controls visited the emergency department of the same hospital for trauma
or fractures (excluding burns) and used allopurinol, carbamazepine or phenytoin
during the past 3 months. We determined whether patients were prescribed a
combination of drugs in addition to allopurinol, carbamazepine or phenytoin
within the last 3 months. We identified 1 853 985 controls and 7327 SJS-diagnosed
patients using the Taiwan NHIRD records for 2000-2008. Higher use of allopurinol
(49.8%), carbamazepine (39.1%) or phenytoin (21.3%) was observed among patients
(n = 3131) than among controls (n = 2858). The overall SJS incidence rate was
3.6/1 000 000. Drug combinations were uncommon (<10%) in patients or controls
taking allopurinol. However, combination drug use exceeded 10% in patients taking
carbamazepine or phenytoin. Logistic regression analysis of recent combination
drug use revealed that phenobarbital, valproate, non-steroidal anti-inflammatory
drugs (NSAIDs) including piroxicam and tenoxicam, and antibiotics including
amoxicillin and cephalexin were strongly associated with SJS. Patients with gout
or epilepsy taking allopurinol, carbamazepine or phenytoin should be evaluated
carefully by physicians. Concurrent use of piroxicam, tenoxicam, phenobarbital,
valproate, amoxicillin or cephalexin, in addition to carbamazepine or phenytoin,
may increase the incidence of SJS.
PMID- 29963718
TI - Chronological clinicopathological characterization of rapidly progressive
alopecia areata resistant to multiple i.v. corticosteroid pulse therapies: An
implication for improving the efficacy.
AB - Intravenous corticosteroid pulse therapy (pulse therapy) has been reported to be
effective for rapidly progressive alopecia areata (RP-AA). Mostly, a single 3-day
administration of corticosteroid (methylprednisolone 500 mg/day) has been
performed in Japan; however, to what extent additional administrations improve
the outcome has not been fully elucidated. To assess the advantage of repeating
the pulse therapy to RP-AA cases refractory to the initial intervention,
retrospective clinicopathological analysis was performed. Detailed chronological
analysis was conducted in eight cases (one man and seven women; average age, 38.3
+/- 10.4 years) demonstrating total scalp hair loss 3 months after the first
pulse therapy and treated with additional rounds of the pulse therapy. All cases
manifested total hair loss, scalp edema, itch or pain on the scalp after the
initial intervention. Histopathological analyses of affected lesions prior to
additional pulse therapies revealed persisting dense perifollicular lymphocytic
inflammation in all cases. Interestingly, such inflammatory change tended to be
severer when compared with previously reported pulse therapy good responders.
Extra pulse therapy resulted in partial regrowth of terminal hairs in three out
of eight cases, but all of them experienced relapse in the long run. The
literature review also suggested limited efficacy of repeating pulse therapy to
severe AA cases. These findings suggested that the efficacy of currently
conducted repetitive pulse therapy is limited in RP-AA cases with extensive
perifollicular inflammation and resistant to the initial pulse therapy.
Modulation of the dose and the interval of intervention, in combination with
alternative approaches, may be required to achieve a successful outcome.
PMID- 29963719
TI - FAM83G/Fam83g genetic variants affect canine and murine hair formation.
AB - FAM83G/Fam83g genetic variants have been described in dogs, mice and recently
also in humans. They are associated with palmoplantar keratoderma and altered
hair or coat phenotype, reported as wooly phenotype in mice. FAM83G/Fam83g is an
unexplored effector of temporally and spatially coordinated Wnt and BMP
signalling which are key pathways in pre- and postnatal hair follicle
morphogenesis and differentiation. The aim of this study was to unravel
phenotypic consequences of FAM83G/Fam83g variants on hair coat formation in dogs
and mice. Our results show differences in hair types and hair shaft structures in
both species. Additionally, mice exhibit deregulated hair cycle progression which
timely correlates with defective Wnt signalling (Axin2) and Bmp2/4 expression.
These results affirm the involvement of FAM83G in hair morphogenesis, hair
follicle differentiation and cycling.
PMID- 29963720
TI - Constructing content validity of clinical nurse specialist core competencies:
exploratory sequential mixed-method study.
AB - RATIONAL: The demand to increase nursing competence is brought on by the
requirement of safe, accessible and more effective use of healthcare provider
expertise. Clinical nurse specialist competency development dates back to the
late 20th century; however, an examination of the literature reveals a lack of
research and discussion to support the competency development. OBJECTIVES: To
describe the formulation and validation process of the clinical nurse specialist
core competencies. DESIGN: Exploratory sequential mixed-method design. METHODS:
This mixed-method study, conducted between 2013 and 2017 in Finland, involved
four phases: I) a Policy Delphi study (n = 25, n = 22, n = 19); II) cross-mapping
of preliminary competency criteria against international competency sets; III)
content validity study of expanded competency criteria (n = 7, n = 10); and IV)
verification of competency criteria with practicing CNSs (n = 16). Data were
analysed by both qualitative and quantitative analysis methods. RESULTS: Seventy
four preliminary clinical nurse competency criteria were formulated in the first
phase of the study. Through cross-mapping the competencies against the US and
Canadian clinical nurse specialist competency sets, they were further concised to
61 criteria. The examination of Content Validity Indexes and experts' comments
led to the clarification and consequent inclusion of 50 criteria to the final
scale, with Scale Content Validity Index Average of 0.94. The competency criteria
were evaluated to be a solid set with potential to clarify and uniform the
clinical nurse specialist roles. CONCLUSIONS: Through a rigorous research
process, validated clinical nurse specialist competency criteria were formed with
a high Scale Content Validity Index Average. The results allude to the potential
of formulating international competency criteria to support global role clarity
and understanding. However, further research is needed to validate the content
and construct of the formulated competencies with a larger population across
countries.
PMID- 29963721
TI - Evaluation of the enhanced recovery after surgery protocol in living liver
donors.
AB - BACKGROUND: Enhanced recovery after surgery (ERAS) protocol has proven to be
effective in many surgery fields in controlling pain and promoting early
recovery. Application of the (ERAS) protocol in living donor liver patients is a
new step to promote early recovery. METHODS: We analyzed outcomes in two groups.
Group A included the living donors who had the ERAS protocol applied (n = 30),
and Group B included donors who had their surgery before the ERAS protocol (n =
30). All donors had the same incision. The ERAS protocol involved a multimodality
methods. This included intravenous ketamine and lidocaine intraoperatively with
single dose intrathecal morphine and local injection of long-acting bupivacaine.
The postoperative regimen included intravenous ketamine, lidocaine, ketorolac,
and narcotics as PRN. RESULTS: Pain on the first three postoperative days was
significantly lower in Group A (P < 0.05). Narcotics were also significantly
lower in Group A (P < 0.01). Return of bowel function occurred earlier by 1 day
in Group A (P < 0.003). Group A patients could tolerate a regular diet by
postoperative day (POD) three vs four in Group B patients (P = 0.0057). Mean
length of stay was lower in Group A, but not statistically significant.
CONCLUSIONS: Enhanced recovery after surgery protocol was effective in minimizing
postoperative pain and helped to decrease the postoperative narcotics and helped
early recovery.
PMID- 29963722
TI - Drivers of postfire soil organic carbon accumulation in the boreal forest.
AB - The accumulation of soil carbon (C) is regulated by a complex interplay between
abiotic and biotic factors. Our study aimed to identify the main drivers of soil
C accumulation in the boreal forest of eastern North America. Ecosystem C pools
were measured in 72 sites of fire origin that burned 2-314 years ago over a vast
region with a range of ? mean annual temperature of 3 degrees C and one of ? 500
mm total precipitation. We used a set of multivariate a priori causal hypotheses
to test the influence of time since fire (TSF), climate, soil physico-chemistry
and bryophyte dominance on forest soil organic C accumulation. Integrating the
direct and indirect effects among abiotic and biotic variables explained as much
as 50% of the full model variability. The main direct drivers of soil C stocks
were: TSF >bryophyte dominance of the FH layer and metal oxide content >pH of the
mineral soil. Only climate parameters related to water availability contributed
significantly to explaining soil C stock variation. Importantly, climate was
found to affect FH layer and mineral soil C stocks indirectly through its effects
on bryophyte dominance and organo-metal complexation, respectively. Soil texture
had no influence on soil C stocks. Soil C stocks increased both in the FH layer
and mineral soil with TSF and this effect was linked to a decrease in pH with TSF
in mineral soil. TSF thus appears to be an important factor of soil development
and of C sequestration in mineral soil through its influence on soil chemistry.
Overall, this work highlights that integrating the complex interplay between the
main drivers of soil C stocks into mechanistic models of C dynamics could improve
our ability to assess C stocks and better anticipate the response of the boreal
forest to global change.
PMID- 29963723
TI - Accelerating forest loss in Southeast Asian Massif in the 21st century: A case
study in Nan Province, Thailand.
AB - Farmers are carving a new agricultural frontier from the forests in the Southeast
Asian Massif (SAM) in the 21st century, triggering significant environment
degradation at the local scale; however, this frontier has been missed by
existing global land use and forest loss analyses. In this paper, we chose
Thailand's Nan Province, which is located in the geometric center of SAM, as a
case study, and combined high resolution forest cover change product with a fine
scale land cover map to investigate land use dynamics with respect to topography
in this region. Our results show that total forest loss in Nan Province during
2001-2016 was 66,072 ha (9.1% of the forest cover in 2000), and that the majority
of this lost forest (92%) had been converted into crop (mainly corn) fields by
2017. Annual forest loss is significantly correlated with global corn price (p <
0.01), re-confirming agricultural expansion as a key driver of forest loss in Nan
Province. Along with the increasing global corn price, forest loss in Nan
Province has accelerated at a rate of 2,616 +/- 730 ha per decade (p < 0.01).
Global corn price peaked in 2012, in which year annual forest loss also reached
its peak (7,523 ha); since then, the location of forest loss has moved to steeper
land at higher elevations. Spatially, forest loss driven by this smallholder
agricultural expansion emerges as many small patches that are not recognizable
even at a moderate spatial resolution (e.g. 300 m). It explains how existing
global land use/cover change products have missed the widespread and rapid forest
loss in SAM. It also highlights the importance of high-resolution observations to
evaluate the environmental impacts of agricultural expansion and forest loss in
SAM, including, but not limited to, the impacts on the global carbon cycle,
regional hydrology, and local environmental degradation.
PMID- 29963724
TI - BAY 94-9027, a PEGylated recombinant factor VIII, exhibits a prolonged half-life
and higher area under the curve in patients with severe haemophilia A:
Comprehensive pharmacokinetic assessment from clinical studies.
AB - INTRODUCTION: Recombinant factor VIII (rFVIII) products with extended half-lives,
such as BAY 94-9027, can potentially maintain higher FVIII levels for longer
periods of time, thus providing improved bleeding protection vs standard-acting
FVIII products. AIM: To characterize the pharmacokinetic (PK) profile of BAY 94
9027 from phase 1, phase 2/3 (PROTECT VIII) and phase 3 (PROTECT VIII Kids)
clinical trials in adults, adolescents and children with severe haemophilia A
METHODS: Patients with severe haemophilia A (FVIII <1%) with >50 FVIII exposure
days (EDs) and no history of inhibitors were included in the phase 1 (18-65
years, >=150 EDs), PROTECT VIII (12-65 years, >=150 EDs) and PROTECT VIII Kids
(<12 years, >50 EDs) trials. PK parameters were assessed following a 25-IU/kg or
60-IU/kg BAY 94-9027 dose in the phase 1 study after the first and repeated
infusion, in PROTECT VIII after the first and repeated 60-IU/kg infusion and in
PROTECT VIII Kids after a single 60-IU/kg infusion. The chromogenic assay was
used to assess FVIII activity. RESULTS: Compared with sucrose-formulated rFVIII,
BAY 94-9027 had reduced clearance that resulted in a ~1.4-fold increase in half
life and dose-normalized area under the curve (AUC). The BAY 94-9027 PK profile
was comparable after single- and repeated-dose administrations. Dose-proportional
increases were observed between 25- and 60-IU/kg administrations. BAY 94-9027 PK
characteristics were age dependent, consistent with other FVIII products.
CONCLUSIONS: BAY 94-9027 shows an extended half-life and increased AUC vs
standard-acting FVIII products. These PK characteristics will result in higher
FVIII levels for longer duration.
PMID- 29963725
TI - A functional study of the global transcriptional regulator PadR from a strain
Streptomyces fradiae-nitR+bld, resistant to nitrone-oligomycin.
AB - We describe Streptomyces fradiae mechanisms of sensitivity to nitrone-oligomycin
A, a derivative of oligomycin A. We obtained S. fradiae-nitR+ bld, a nitrone
oligomycin A resistant mutant with a "bald" phenotype. Comparative genomic
analysis of the wild-type S. fradiae ATCC19609 and S. fradiae-nitR+ bld revealed
a mutation in padR - a gene encoding a multifunction transcription regulator,
which resulted in the amino acid replacement in a highly conserved DNA-binding
domain. Bioinformatics genome analysis of S. fradiae ATCC19609 discovered a PadR
binding site 13 bp upstream the start codon of the marR transcription factor
gene. Induction of S. fradiaenitR+ bld and w.t. strains with nitrone-oligomycin A
lead to a significant increase in expression level of the marR gene in the w.t.
strain, but no change observed in mutant strain. We identified differences
between DNA-protein interactions of the mutant and native PadR proteins with its
putative binding site in S. fradiae ATCC19609. This allowed us to suggest that
the padR gene, that harbored a single nucleotide mutation in the S. fradiaenitR+
bld strain, might be involved in the mechanism of resistance to nitrone
oligomycin A. We assume the participation of the transcriptional factorpadR in
the formation of the bald phenotype.
PMID- 29963726
TI - Evaluation of the secretion of antimicrobial peptides and antimicrobial effect of
skin wash in atopic and healthy dogs: a preliminary study.
AB - BACKGROUND: Antimicrobial peptides (AMPs) are an important component of cutaneous
innate immunity. The amount of AMPs secreted in healthy and atopic patients is
controversial. HYPOTHESES/OBJECTIVES: To evaluate the antimicrobial effect of
skin wash harvested from healthy and atopic dogs, the amount of AMPs (cBD3
like/cBD122, cCath, S100A8/9/12) present in the skin washes, and the correlation
between AMP levels and severity of the clinical signs. ANIMALS: Fifteen healthy
and 15 mildly atopic, privately owned dogs. METHODS AND MATERIALS: Skin washes
were performed on a 15 cm2 area of nonlesional abdominal skin. The area was
rinsed with 2.7 mL of saline using a sterile tube. Commercially available
(S100A8/9/12) or in-house (cBD3-like and cCath) canine-specific ELISAs were
performed. Skin washes were incubated with different concentrations (5 * 105 to 4
* 103 cfu/mL) of Staphylococcus pseudintermedius and the bacterial density
measured after 24 h of incubation. Severity of clinical signs was assessed by the
Canine Atopic Dermatitis Extent and Severity Index, 4th version (CADESI-04). Data
were analysed statistically and significance level was set as P <= 0.05. RESULTS:
There was no significant difference in any of the tested AMPs between healthy and
atopic dogs. Strong/moderate positive correlations were seen between total and
inguinal CADESI-04 (r = 0.69; P = 0.0061) and between AMPs [cBD3-like/cCath (r =
0.69; P = 0.011), S100A8/S100A9 (r = 0.8; P = 0.0016) and S100A9/S100A12 (r =
0.57; P = 0.047)]. Significantly less antimicrobial activity was seen in skin
washes from atopic versus healthy dogs (P < 0.05). CONCLUSIONS AND CLINICAL
IMPORTANCE: This study found no difference in AMP secretion levels between
healthy and nonlesional atopic canine skin. However, a significantly lower
antimicrobial activity was present in the skin washes from atopic compared to
healthy skin.
PMID- 29963727
TI - Engaging the patient: improving dietary intake and meal experience through
bedside terminal meal ordering for oncology patients.
AB - BACKGROUND: The present study aimed to determine changes in patient dietary
intake, plate waste and meal experience associated with the implementation of a
patient-directed bedside electronic meal ordering system (BMOS) compared to
traditional paper menus (PMs). METHODS: The study evaluated the effect of a BMOS
compared to PM at an oncology hospital between 2015 and 2016. Patient dietary
intake, plate waste and patient meal experience were the key outcomes measured.
Plate waste was determined using a validated seven-point visual wastage scale.
The weight eaten estimates were converted into nutrients consumed in each food
item to estimate dietary intake. Patient meal experience was measured via written
surveys. RESULTS: There was an increase in patient dietary intake and patient
meal experience, with BMOS compared to PM. Comparison between BMOS (n = 105) and
PM (n = 96) showed statistically significant increases in ordering sufficient
energy (8683 kJ day-1 versus 6773 kJ day-1 , P = 0.004) and protein (97 g day-1
versus 82 g day-1 , P = 0.023), as well as average energy intake (6457 kJ day-1
versus 4805 kJ day-1 , P < 0.001) and protein intake (73 g day-1 versus 58 g day
1 , P < 0.001). Average plate waste remained the same for both cohorts. Patient
meal experience showed that 60% of patients accessed the BMOS independently. The
BMOS cohort had significant increases in receiving the food that they ordered (P
< 0.001) and in choosing food that they liked (P = 0.006). CONCLUSIONS: The
results of the present study demonstrate that a patient-directed electronic meal
ordering system improved patient dietary intake and meal experience. These
results are most likely a result of empowering patients to make decisions about
their meal selections and nutritional care through accessible meal ordering and
improved menu communication.
PMID- 29963728
TI - In vitro effects of FBXW7 mutation in serous endometrial cancer: Increased levels
of potentially druggable proteins and sensitivity to SI-2 and dinaciclib.
AB - Serous endometrial cancers (ECs) are clinically aggressive tumors that frequently
harbor somatic mutations in FBXW7 (F-box and WD repeat domain-containing 7). The
FBXW7 tumor suppressor is part of a SCF (complex of SKP1, Cullin 1, F-box
protein) ubiquitin ligase complex which controls the degradation of numerous
substrates that, if not properly regulated, can contribute to the initiation or
progression of tumorigenesis. Despite reports that up to 30% of serous ECs
include somatic mutations in FBXW7, the molecular effects of mutated FBXW7 in ECs
have not been determined. Here, we used transient transfection and Clustered
Regularly Interspaced Short Palindromic Repeats (CRISPR) editing in serous EC
cell lines to interrogate the molecular effects of six recurrent FBXW7 mutations.
We show that FBXW7 mutations lead to increased Cyclin E1, steroid receptor
coactivator 3 (SRC-3), c-MYC, Rictor, glycogen synthase kinase 3 (GSK3), P70S6
kinase, and protein kinase B (AKT) phosphorylated protein levels in serous EC
cells. Furthermore, we demonstrate that CRISPR-edited FBXW7-mutant ARK1 serous EC
cells exhibit increased sensitivity to SI-2 (a SRC inhibitor) and dinaciclib (a
cyclin dependent kinase (CDK) inhibitor) compared to parental ARK1 cells.
Collectively, our findings reveal biochemical effects of FBXW7 mutations in the
context of EC and provide in vitro evidence of sensitivity to targeted
inhibitors.
PMID- 29963729
TI - Sleep-disordered breathing and electrocardiographic QRS-T angle: The MESA study.
AB - INTRODUCTION: Sleep-disordered breathing (SDB) has been linked to sudden cardiac
death (SCD) but the mechanism is unclear. Abnormal QRS-T angle, a novel
electrocardiographic (ECG) marker of ventricular repolarization, has been linked
to adverse cardiovascular outcomes including SCD. We hypothesized that
individuals with SDB have more pronounced abnormality in QRS-T angle. METHODS: We
performed a cross-sectional analysis from the Multi-Ethnic Study of
Atherosclerosis (MESA) Exam Sleep ancillary study. We calculated the odds ratio
(OR) of abnormal frontal and spatial QRS-T angle (defined as >sex-specific 95th
percentile thresholds) related to the apnea-hypopnea index (AHI) using logistic
regression, adjusting for demographics, body habitus, cardiovascular risks, and
prevalent cardiovascular disease. Linear associations between AHI and frontal and
spatial QRS-T angle, separately, were also examined using multiple regression
models. RESULTS: A total of 1,804 participants (mean age 67.9 (+/-9.0) years,
55.3% women and 64.1% non-whites) were included in the study. Sleep-disordered
breathing was common among participants (median AHI 8.6 events/hr IQR [3.2
19.5/hr]). Higher AHI was associated with the odds of abnormal frontal (>=81
degrees in men and >=79 degrees in women) and spatial QRS-T angle (>=129.7
degrees in men and >=115.9 degrees in women; OR [95%CI]: 1.25 [1.02-1.51], p =
0.03; 1.23 [1.01-1.50], p = 0.04 respectively per 1 SD [16.8 events/hr] increase
in AHI). Similarly, linear associations were observed (frontal QRS-T angle: beta
coefficient: 2.30 degrees [0.92, 3.66], p = 0.001; spatial QRS-T angle: beta
coefficient: 2.16 degrees [0.67, 3.64], p = 0.005). CONCLUSION: In a
racially/ethnically diverse community cohort, severity of SDB is associated with
abnormal ventricular repolarization as measured by QRS-T angle.
PMID- 29963731
TI - Life-history traits buffer against heat wave effects on predator-prey dynamics in
zooplankton.
AB - In addition to an increase in mean temperature, extreme climatic events, such as
heat waves, are predicted to increase in frequency and intensity with climate
change, which are likely to affect organism interactions, seasonal succession,
and resting stage recruitment patterns in terrestrial as well as in aquatic
ecosystems. For example, freshwater zooplankton with different life-history
strategies, such as sexual or parthenogenetic reproduction, may respond
differently to increased mean temperatures and rapid temperature fluctuations.
Therefore, we conducted a long-term (18 months) mesocosm experiment where we
evaluated the effects of increased mean temperature (4 degrees C) and an
identical energy input but delivered through temperature fluctuations, i.e., as
heat waves. We show that different rotifer prey species have specific temperature
requirements and use limited and species-specific temperature windows for
recruiting from the sediment. On the contrary, co-occurring predatory cyclopoid
copepods recruit from adult or subadult resting stages and are therefore able to
respond to short-term temperature fluctuations. Hence, these different life
history strategies affect the interactions between cyclopoid copepods and
rotifers by reducing the risk of a temporal mismatch in predator-prey dynamics in
a climate change scenario. Thus, we conclude that predatory cyclopoid copepods
with long generation time are likely to benefit from heat waves since they
rapidly "wake up" even at short temperature elevations and thereby suppress fast
reproducing prey populations, such as rotifers. In a broader perspective, our
findings suggest that differences in life-history traits will affect predator
prey interactions, and thereby alter community dynamics, in a future climate
change scenario.
PMID- 29963730
TI - Establishment and characterization of a canine keratinocyte organoid culture
system.
AB - BACKGROUND: Perturbations of epidermal and follicular homeostasis have been
attributed to a variety of skin diseases affecting dogs. The availability of an
in vitro system to investigate these diseases is important to understand
underlying pathomechanisms. OBJECTIVES: To establish an accurate and reliable in
vitro 3D system of canine keratinocyte organoids to lay the basis for studying
functional defects in interfollicular epidermis (IFE) and hair follicle (HF)
morphogenesis, reconstitution and differentiation that lead to alopecic and
epidermal diseases. ANIMALS: Skin biopsies were obtained from freshly euthanized
dogs of different breeds with no skin abnormalities. METHODS: Cells derived from
microdissected IFE and HFs were seeded in Matrigel and keratinocyte organoids
were grown and characterized using immunohistochemistry, RT-qPCR and RNA
sequencing. RESULTS: Both organoid lines develop into a basal IFE-like cell type.
Gene and protein expression analysis revealed high mRNA and protein levels of
keratins 5 and 14, IFE differentiation markers and intercellular molecules. Key
markers of HF stem cells were lacking. Withdrawal of growth factors resulted in
upregulation of markers such as KRT16, Involucrin, KRT17 and SOX9, showing the
potential of the organoids to develop towards more differentiated tissue.
CONCLUSION AND CLINICAL IMPORTANCE: Our 3D in vitro culture system provides the
basis to explore epidermal function, to investigate the culture conditions
necessary for the development of organoids with a HF signature and to address
cutaneous disorders in dogs. However, for induction of HF signatures or hair
growth, addition of different growth factors or co-culture with dermal papilla
will be required.
PMID- 29963732
TI - Prognostic implications of microvascular complications in patients with diabetes
and heart failure with reduced ejection fraction.
PMID- 29963733
TI - Effects of a short-term Interval Aerobic Training Programme with active Recovery
bouts (IATP-R) on cognitive and mental health, functional performance and quality
of life: A randomised controlled trial in sedentary seniors.
AB - BACKGROUND: Interval aerobic training programme with active recovery bouts (IATP
R) has shown to improve tolerance to IATP among seniors. However, data concerning
its benefits for seniors' health are still limited. PURPOSE: The purpose of this
study was to examine the effects of IATP-R on seniors' health status. METHODS:
Sedentary volunteers (n = 60, aged >=70 years) were randomly assigned to either
IATP-R or maintained sedentary lifestyle for 9.5 weeks. IATP-R consisted of 30
minute cycling (6 * 4 minutes at first ventilatory threshold (VT1 ) intensity + 1
minute at 40% of VT1 ) twice a week. Cognitive and functional performances were
assessed with the Trail Making Test (TMT-A; TMT-B); Paced Auditory Serial
Addition Test (PASAT); Timed Up and Go (TUG) test; 6-Minute Walk Test (6-MWT);
one-leg balance test; and the Short Physical Performance Battery (SPPB) tests,
respectively. QoL and anxiety/depression status were measured by the Short Form
12 and the Goldberg's Scale, respectively. All participants were assessed at
baseline and 9.5 weeks later. RESULTS: Compared to controls, IATP-R improved
cognitive functions (TMT-A: +1.5% vs -21.5%; TMT-B: +0.9% vs -13.3%; PASAT: +1.4%
vs -14.6%; semantic fluency: -1.1% vs +11.7%), functional performance (TUG: +5.4%
vs -16.5%; 6-MWT: -3.2% vs +11.5%; SPPB: -3.2% vs +14.6%; One-leg balance: -16.3%
vs +25.0%); QoL (physical health: -13.3% vs +23.1%; mental health: -7.1% vs
+8.2%); and depressive symptoms (+26.3% vs -42.8%). Significant impacts were
measured neither on letter modality of fluency tasks nor on anxiety score.
CONCLUSION: These data showed that IATP-R is an effective training programme to
improve functional and cognitive performances, mental health and well-being in
sedentary seniors. Trial registration ClinicalTrials.gov NCT02263573. Registered
October 1, 2014.
PMID- 29963734
TI - Children and young people with Down syndrome: Their awareness of Down syndrome
and developing self-perceptions.
AB - BACKGROUND: Past research suggests children with Down syndrome often lack
awareness of their disability despite the visibility of their condition. METHOD:
This study used novel tasks to investigate their insight. Twenty-eight young
people with Down syndrome (aged 8-17 years) were recruited, along with control
groups of 67 typically developing young people. Three tasks explored the
children's awareness of Down syndrome: (a) choice of partner for social
activities, (b) sorting photographs and (c) attributing positive or negative
descriptors to photographs. RESULTS: All participants expressed a preference to
engage in social activities with typically developing peers. Most participants
with Down syndrome identified with the typically developing person. Even though
all participants attributed more positive descriptors to the photographs of the
typically developing individuals, they remained positive about themselves.
CONCLUSION: The early awareness of difference shown by young people with Down
syndrome suggests this may play an important role in their developing identities.
PMID- 29963735
TI - Dynamic responses of tree-ring growth to multiple dimensions of drought.
AB - Droughts, which are characterized by multiple dimensions including frequency,
duration, severity, and onset timing, can impact tree stem radial growth
profoundly. Different dimensions of drought influence tree stem radial growth
independently or jointly, which makes the development of accurate predictions a
formidable challenge. Measurement-based tree-ring data have obvious advantages
for studying the drought responses of trees. Here, we explored the use of
abundant tree-ring records for quantifying regional response patterns to key
dimensions of drought. Specifically, we designed a series of regional-scaled
"natural experiments," based on 357 tree-ring chronologies from Southwest USA and
location-matched monthly water balance anomalies, to reveal how tree-ring
responds to each dimension of drought. Our results showed that tree-ring was
affected significantly more by the water balance condition in the current
hydrological year than that in the prior hydrological year. Within the current
hydrological year, increased drought frequency (number of dry months) and
duration (maximum number of consecutive dry months) resulted in "cumulative
effects" which amplified the impacts of drought on trees and reduced the drought
resistance of trees. Drought events that occurred in the pregrowing seasons
strongly affected subsequent tree stem radial growth. Both the onset timing and
severity of drought increased "legacy effects" on tree stem radial growth, which
reduced the drought resilience of trees. These results indicated that the drought
impact on trees is a dynamic process: even when the total water deficits are the
same, differences among the drought processes could lead to considerably
different responses from trees. This study thus provides a conceptual framework
and probabilistic patterns of tree-ring growth response to multiple dimensions of
drought regimes, which in turn may have a wide range of implications for
predictions, uncertainty assessment, and forest management.
PMID- 29963736
TI - Talking about palliative care in heart failure.
PMID- 29963737
TI - Waist-to-hip ratio and mortality in heart failure.
AB - AIMS: A higher body mass index (BMI) is associated with better survival in heart
failure (HF) patients, also known as the obesity paradox. However, BMI does not
account for body composition. We therefore analysed the association between
abdominal fat, measured via waist-to-hip ratio (WHR), BMI and all-cause mortality
in patients with HF. METHODS AND RESULTS: For this analysis, 1738 patients from
the Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure
(BIOSTAT-CHF) validation study were included. Patients without waist and hip
measurements were excluded. WHR was defined as waist circumference/hip
circumference, divided into tertiles and split for sex. A linear regression of
principal components from an extensive panel of biomarkers was performed to
provide insight in the pathophysiology behind a higher WHR. In total, 1479
patients were included, of which 33% were female and mean age was 75 +/-11 years.
A higher WHR was independently associated with a higher BMI, a higher prevalence
of diabetes and higher New York Heart Association functional class. There was a
significant interaction between sex and WHR on its association with mortality (P
<0.001). In women, a higher WHR was associated with a higher mortality risk
[hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.37-3.63; P =0.001],
whereas no significant association was found in men (HR 0.87, 95% CI 0.63-1.20; P
= 0.409). We found a strong association between a higher WHR and elevated markers
of inflammation and MAPK cascade in women, while these associations were less
profound in men. CONCLUSIONS: A higher WHR was associated with a higher risk of
death in female but not in male HF patients. These findings challenge the obesity
paradox, and suggest that fat deposition is pathophysiologically harmful and may
be a target for therapy in female patients with HF.
PMID- 29963738
TI - meta-Cyanobenzyl substituted benzimidazolium salts: Synthesis, characterization,
crystal structure and carbonic anhydrase, alpha-glycosidase,
butyrylcholinesterase, and acetylcholinesterase inhibitory properties.
AB - meta-Cyanobenzyl-substituted N-heterocyclic carbene (NHC) precursors were
synthesized by the reaction of a series of N-(alkyl)benzimidazolium with 3
bromomethyl-benzonitrile. These benzimidazolium salts were characterized by using
1 H NMR, 13 C NMR, FTIR spectroscopy, and elemental analysis techniques. The
molecular and crystal structures of 2f and 2g complexes were obtained by using
the single-crystal X-ray diffraction method. The derivatives of these novel NHC
precursors were effective inhibitors of alpha-glycosidase (AG), the cytosolic
carbonic anhydrase I and II isoforms (hCA I and II), butyrylcholinesterase
(BChE), and acetylcholinesterase (AChE) with Ki values in the range of 1.01-2.12
nM for AG, 189.56-402.44 nM for hCA I, 112.50-277.37 nM for hCA II, 95.45-352.58
nM for AChE, and 132.91-571.18 nM for BChE. In the last years, inhibition of the
CA enzyme has been considered as a promising factor for pharmacologic
intervention in a diversity of disturbances such as obesity, glaucoma, cancer,
and epilepsy.
PMID- 29963739
TI - Design, synthesis, in vitro and in silico evaluation of new pyrrole derivatives
as monoamine oxidase inhibitors.
AB - In an effort to develop potent monoamine oxidase (MAO) inhibitors, new pyrrole
derivatives were obtained via the selective reduction of the C?C bonds of 1-(1
methyl-1H-pyrrol-2-yl)-3-[5-(aryl)furan-2-yl]prop-2-en-1-ones through palladium
catalyzed hydrogenation in ethanol. The synthesized compounds were screened for
their inhibitory effects on MAO-A and MAO-B by an in vitro fluorometric method.
The selectivity index (SI) value was given as the ratio of IC50 (MAO-A)/IC50 (MAO
B) for each compound. 3-(5-(4-Chlorophenyl)furan-2-yl)-1-(1-methyl-1H-pyrrol-2
yl)propan-1-one (6) was identified as the most selective MAO-A inhibitor in this
series, with an IC50 value of 0.162 uM and a SI value of 0.002. Kinetic studies
were also carried out to assess the nature of MAO-A inhibition by compound 6.
According to Lineweaver-Burk plots, compound 6 was found to be a competitive MAO
A inhibitor and the Ki value of compound 6 was determined as 0.1221 MUM. Docking
studies were performed for compound 6 and clorgyline using the human MAO-A
crystal structure (PDB ID: 2Z5Y). The docking results showed that compound 6
presented similar interactions as clorgyline in the active center cavity of the
enzyme. Molinspiration software was used to determine the physicochemical
parameters of all compounds for an evaluation of their compliance to Lipinski's
rule of five. Compound 6 did not violate Lipinski's rule, making it a potential
orally bioavailable therapeutic agent.
PMID- 29963740
TI - Quantifying Wildlife and Navigation Benefits of a Dredging Beneficial-Use Project
in the Lower Atchafalaya River: A Demonstration of Engineering with Nature(r).
AB - The US Army Corps of Engineers (USACE) operates and maintains numerous projects
in support of its various civil works missions including flood damage risk
reduction, navigation, and ecosystem restoration. Originally authorized on an
economic basis, these projects may produce a broad array of unaccounted for
ecosystem services (ESs) that contribute to overall human, societal, and
environmental well-being. Efforts are underway to capture the full array of
environmental, economic, and social impacts of these projects. Methods are needed
to identify relevant ESs generated by these nature-based projects and to measure
their contribution to societal well-being with an emphasis placed on use of
readily available data. Performance metrics were collected to capture the
benefits of strategic placement of dredged material in river systems to allow
formation of islands that produce a wide array of ESs. These performance metrics
can be converted to ESs with market value or combined in a decision analytical
approach to demonstrate the relative gain in utility. This approach is
demonstrated on a riverine island created on the Atchafalaya River, Louisiana, as
a result of the strategic placement of dredged material. The outcomes foster
integration of ES assessment into project design and management practices and
support more comprehensive project evaluation and widespread application. Integr
Environ Assess Manag 2018;14:759-768. Published 2018. This article is a US
Government work and is in the public domain in the USA.
PMID- 29963741
TI - Climatic, topographic, and anthropogenic factors determine connectivity between
current and future climate analogs in North America.
AB - As climatic conditions shift in coming decades, persistence of many populations
will depend on their ability to colonize habitat newly suitable for their
climatic requirements. Opportunities for such range shifts may be limited unless
areas that facilitate dispersal under climate change are identified and protected
from land uses that impede movement. While many climate adaptation strategies
focus on identifying refugia, this study is the first to characterize areas which
merit protection for their role in promoting climate connectivity at a
continental extent. We identified climate connectivity areas across North America
by delineating paths between current climate types and their future analogs that
avoided nonanalogous climates, and used centrality metrics to rank the
contribution of each location to facilitating dispersal across the landscape. The
distribution of connectivity areas was influenced by climatic and topographic
factors at multiple spatial scales. Results were robust to uncertainty in the
magnitude of future climate change arising from differing emissions scenarios and
general circulation models, but sensitive to analysis extent and assumptions
concerning dispersal behavior and maximum dispersal distance. Paths were funneled
along north-south trending passes and valley systems and away from areas of novel
and disappearing climates. Climate connectivity areas, where many potential
dispersal paths overlapped, were distinct from refugia and thus poorly captured
by many existing conservation strategies. Existing protected areas with high
connectivity values were found in southern Mexico, the southwestern US, and
western and arctic Canada and Alaska. Ecoregions within the Isthmus of
Tehuantepec, Great Plains, eastern temperate forests, high Arctic, and western
Canadian Cordillera hold important climate connectivity areas which merit
increased conservation focus due to anthropogenic pressures or current low levels
of protection. Our coarse-filter climate-type-based results complement and
contextualize species-specific analyses and add a missing dimension to climate
adaptation planning by identifying landscape features which promote connectivity
among refugia.
PMID- 29963743
TI - Controlled before-after study to evaluate change in evidence-based practice of
speech and language therapy students.
AB - BACKGROUND: The integration of evidence-based practice (EBP) into speech and
language therapy (SLT) curricula has been increasingly encouraged in recent
years. OBJECTIVES: The study aimed to evaluate whether an educational module on
EBP for undergraduate SLT students can improve their EBP competencies. METHODS:
The EBP module, taught by a SLT faculty member and a librarian, was delivered
over 2 months. All fourth year SLT students (trained group) and all fourth year
psychology students (control group) of the University of Liege (Belgium) were
asked to participate in the study. Their performance on an adapted Fresno test
was measured before and after the module. In addition, the SLT students took a
computer-based searching task. They were also asked to share their perceptions
towards the module. RESULTS: All the 47 SLT students and 57/108 psychology
students took the pre- and post-tests. Although both groups performed similarly
at the baseline, only the trained students gained new skills and knowledge.
Furthermore, 36 SLT students shared their perceptions on the module and offered
suggestions on ways to improve it. DISCUSSION-CONCLUSION: Trained students
improved their EBP competencies. Nevertheless, the module could be strengthened
along with better integration of EBP into clinical modules and across the
curriculum.
PMID- 29963742
TI - Systems pathology analysis identifies neurodegenerative nature of age-related
vitreoretinal interface diseases.
AB - Aging is a phenomenon that is associated with profound medical implications.
Idiopathic epiretinal membrane (iEMR) and macular hole (MH) are the major vision
threatening vitreoretinal diseases affecting millions of aging people globally,
making these conditions an important public health issue. iERM is characterized
by fibrous tissue developing on the surface of the macula, which leads to
biomechanical and biochemical macular damage. MH is a small breakage in the
macula and is associated with many ocular conditions. Although several individual
factors and pathways are suggested, a systems pathology level understanding of
the molecular mechanisms underlying these disorders is lacking. Therefore, we
performed mass spectrometry-based label-free quantitative proteomics analysis of
the vitreous proteomes from patients with iERM and MH to identify the key
proteins, as well as the multiple interconnected biochemical pathways,
contributing to the development of these diseases. We identified a total of 1,014
unique proteins, many of which are linked to inflammation and the complement
cascade, revealing the inflammation processes in retinal diseases. Additionally,
we detected a profound difference in the proteomes of iEMR and MH compared to
those of diabetic retinopathy with macular edema and rhegmatogenous retinal
detachment. A large number of neuronal proteins were present at higher levels in
the iERM and MH vitreous, including neuronal adhesion molecules, nervous system
development proteins, and signaling molecules, pointing toward the important role
of neurodegenerative component in the pathogenesis of age-related vitreoretinal
diseases. Despite them having marked similarities, several unique vitreous
proteins were identified in both iERM and MH, from which candidate targets for
new diagnostic and therapeutic approaches can be provided.
PMID- 29963745
TI - Acceleration of global vegetation greenup from combined effects of climate change
and human land management.
AB - Global warming and human land management have greatly influenced vegetation
growth through both changes in spring phenology and photosynthetic primary
production. This will presumably impact the velocity of vegetation greenup
(Vgreenup, the daily rate of changes in vegetation productivity during greenup
period), yet little is currently known about the spatio-temporal patterns of
Vgreenup of global vegetation. Here, we define Vgreenup as the ratio of the
amplitude of greenup (Agreenup) to the duration of greenup (Dgreenup) and derive
global Vgreenup from 34-year satellite leaf area index (LAI) observations to
study spatio-temporal dynamics of Vgreenup at the global, hemispheric, and
ecosystem scales. We find that 19.9% of the pixels analyzed (n = 1,175,453)
experienced significant trends toward higher greenup rates by an average of 0.018
m2 m-2 day-1 for 1982-2015 as compared to 8.6% of pixels with significant
negative trends (p < 0.05). Global distribution and dynamics of Vgreenup show
high spatial heterogeneity and ecosystem-specific patterns, which is primarily
determined by the high spatial variation in Agreenup, while the temporal dynamics
of Vgreenup are directly controlled by both changes in Dgreenup and Agreenup.
Areas with the largest Vgreenup and largest positive trends are both observed in
deciduous and mixed forests as compared to nonforest ecosystems showing both
lower Vgreenup and trends. For nonforest ecosystems, human-managed ecosystems
(e.g., rangelands and rainfed croplands) exhibited higher Vgreenup and positive
trends than those of natural counterparts, suggesting strong imprints of human
land management on terrestrial ecosystem functioning. Globally, warming has
accelerated Vgreenup in temperature-constrained high latitude forest ecosystems
and arctic regions, but decelerated Vgreenup in temperate and arid/semiarid
areas. These results suggest that the combined effects of climate change and
human land management have greatly accelerated global vegetation greenup, with
important implications for changes in terrestrial ecosystem functioning and
global carbon cycling.
PMID- 29963746
TI - FOXO are required for intervertebral disk homeostasis during aging and their
deficiency promotes disk degeneration.
AB - Intervertebral disk (IVD) degeneration is a prevalent age-associated
musculoskeletal disorder and a major cause of chronic low back pain. Aging is the
main risk factor for the disease, but the molecular mechanisms regulating IVD
homeostasis during aging are unknown. The aim of this study was to investigate
the function of FOXO, a family of transcription factors linked to aging and
longevity, in IVD aging and age-related degeneration. Conditional deletion of all
FOXO isoforms (FOXO1, 3, and 4) in IVD using the Col2a1Cre and AcanCreER mouse
resulted in spontaneous development of IVD degeneration that was driven by severe
cell loss in the nucleus pulposus (NP) and cartilaginous endplates (EP).
Conditional deletion of individual FOXO in mature mice showed that FOXO1 and
FOXO3 are the dominant isoforms and have redundant functions in promoting IVD
homeostasis. Gene expression analyses indicated impaired autophagy and reduced
antioxidant defenses in the NP of FOXO-deficient IVD. In primary human NP cells,
FOXO directly regulated autophagy and adaptation to hypoxia and promoted
resistance to oxidative and inflammatory stress. Our findings demonstrate that
FOXO are critical regulators of IVD homeostasis during aging and suggest that
maintaining or restoring FOXO expression can be a therapeutic strategy to promote
healthy IVD aging and delay the onset of IVD degeneration.
PMID- 29963748
TI - Corrigendum.
PMID- 29963749
TI - WEO Newsletter.
PMID- 29963747
TI - 'Hiding in plain sight': Exploring the complexity of sexual safety within an
acute mental health setting.
AB - It is increasingly being recognized that individuals who access acute mental
health services are at risk of sexual assault. Assaults may be perpetrated by
other patients but also by staff working in mental health environments, although
this latter group remain largely under-researched. Following a reported
professional sexual assault and review of an acute inpatient mental health
setting in the UK, the overall aim of this study was to explore the mechanisms
and structures that were put into place following the investigation and in so
doing examine the wider questions of sexual safety in acute mental health
settings. A qualitative approach was utilized and involved interviews with
clinical staff (n = 8). Thematic analysis was used to analyse the data resulting
in four main themes: 'Feeling betrayed': The relational context of the ward
environment'; 'Doing what we were meant to be doing': Quality of leadership';
'Covering yourself': Safeguarding practice; 'The subtleties of abuse':
Complexities of safeguarding '. The findings of the study highlight the need for
clear organizational structures of support, a clearer understanding of 'sexual
safety', and education and training which explicitly addresses recognition and
complexity of sexual violence.
PMID- 29963744
TI - Aging and Alzheimer's disease: Comparison and associations from molecular to
system level.
AB - Alzheimer's disease is the most prevalent cause of dementia, which is defined by
the combined presence of amyloid and tau, but researchers are gradually moving
away from the simple assumption of linear causality proposed by the original
amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that
cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's
disease are intrinsically interwoven with each other, we review and summarize
evidence from molecular, cellular, and system level. In particular, we focus on
study designs, treatments, or interventions in Alzheimer's disease that could
also be insightful in aging and vice versa.
PMID- 29963750
TI - Responsive Fluorescence Probe for Selective and Sensitive Detection of
Hypochlorous Acid in Live Cells and Animals.
AB - The development of effective bioanalytical methods for rapid, sensitive and
specific detection of HOCl in vitro and in vivo plays a key role for better
understanding the roles of this molecule in normal and diseased conditions, but
remains challenging due to the highly reactive nature of HOCl and the complicated
biological conditions. In this work, a new fluorescence probe, PQI, was developed
for monitoring of the HOCl level in biological samples. PQI was easily
synthesized by a one-step condensation reaction. Upon addition of HOCl,
significant changes in the absorption spectra and the color of the solution were
noticed, facilitating the "naked eye" detection of HOCl in PBS buffer. The
fluorescence of PQI was found to be significantly increased within a few seconds,
leading to "OFF-ON" fluorescence response towards HOCl. The sensing mechanism,
oxidation of thioether by HOCl, was confirmed by HRMS titration analysis. PQI
features a large Stokes shift, high sensitivity and selectivity, and rapid
fluorescence response towards HOCl. Quantitative detection of HOCl in single live
cells was demonstrated through fluorescence imaging and flow cytometry analysis.
PQI was then successfully used in visualisation of HOCl in live zebrafish and
nude mice.
PMID- 29963751
TI - Identification of bacteria and fungi sampled from the conjunctival surface of
normal horses in South-East Queensland, Australia.
AB - OBJECTIVE: To identify bacteria and fungi found on the conjunctival surface of
normal horse eyes; to investigate potential risk factors for these microflora;
and to determine their susceptibility to common topical ophthalmic
antimicrobials. ANIMALS STUDIED: A total of 95 client-owned horses were studied.
PROCEDURES: Horses within sub-tropical Australia (South-East Queensland) were
sampled once between April 2012 and March 2013. A conjunctival swab was taken
from each eye and cultured for aerobic bacteria and fungi. Organisms were
identified by colony morphology and phenotype. Antimicrobial disk diffusion
susceptibility testing for commonly used antimicrobials was performed. RESULTS:
Positive bacterial cultures were returned from 187/190 (98.4%) eyes from 94/95
(98.9%) horses. The most common species included Staphylococcus spp. (25.2% of
total bacterial isolates), Bacillus cereus (17.4%), Bacillus spp. (14.1%), and
Corynebacterium spp. (8.9%). Most bacterial isolates were susceptible to neomycin
and fluoroquinolones. Positive fungal cultures were returned from 111/190 (58.4%)
eyes from 73 (76.8%) horses. The most common species identified included:
Penicillium spp. (16.7% of fungal isolates), Aspergillus spp. (15.4%), and
Scopulariopsis spp. (10.3%). Most (>=90%) molds were susceptible to ketoconazole,
voriconazole, itraconazole, and miconazole. Yeasts were most susceptible to
ketoconazole. There was no significant effect of breed, age, sex, purpose, or
housing of the horse or climatic conditions on bacterial or fungal culture
status. CONCLUSIONS: Bacteria and fungi were commonly isolated from the eyes of
healthy horses. The antibiotic and antifungal susceptibilities identified can be
used as a guide for empirical therapy after cytology in the treatment of corneal
ulceration in horses.
PMID- 29963753
TI - Independent determinants of periodontitis in Yemeni adults: A case-control study.
AB - OBJECTIVES: The relative importance of risk factors of periodontitis varies from
one population to another. In this study, we sought to identify independent risk
factors of periodontitis in a Yemeni population. METHODS: One hundred and fifty
periodontitis cases and 150 healthy controls, all Yemeni adults 30-60 years old,
were recruited. Sociodemographic data and history of oral hygiene practices and
oral habits were obtained. Plaque index (PI) was measured on index teeth.
Periodontal health status was assessed using Community Periodontal Index (CPI)
and Clinical Attachment Loss (CAL) according to WHO. Periodontitis was defined as
having one or more sextants with a CPI score >= 3. Multiple logistic regression
modelling was employed to identify distal, intermediate and proximal determinants
of periodontitis, while ordinal regression was used to identify those of CAL
scores. RESULTS: In logistic regression, PI score was associated with the highest
odds of periodontitis (OR = 82.9) followed by cigarette smoking (OR = 12.8),
water pipe smoking (OR = 10.2), male gender (OR = 3.4) and age (OR = 1.19); on
the other hand, regular visits to the dentist (OR = 0.05), higher level of
education (OR = 0.37) and daily dental flossing (OR = 0.95) were associated with
lower odds. Somewhat similar associations were seen for CAL scores (ordinal
regression); however, qat chewing was identified as an additional determinant (OR
= 4.69). CONCLUSION: Water pipe smoking is identified as a risk factor of
periodontitis in this cohort in addition to globally known risk factors. Adjusted
effect of qat chewing is limited to CAL scores, suggestive of association with
recession.
PMID- 29963752
TI - Social decision making in autism: On the impact of mirror neurons, motor control,
and imitative behaviors.
AB - The Mirror Neuron System (MNS) plays a crucial role in action perception and
imitative behavior, which is suggested to be impaired in Autism Spectrum
Disorders (ASDs). In this review, we discuss the plausibility and empirical
evidence of a neural interaction between the MNS, action perception, empathy,
imitative behavior, and their impact on social decision making in ASDs. To date,
there is no consensus regarding a particular theory in ASDs and its underlying
mechanisms. Some theories have completely focused on social difficulties, others
have emphasized sensory aspects. Based on the current studies, we suggest a
multilayer neural network model including the MNS on a first layer and
transforming this information to a higher layer network responsible for
reasoning. Future studies with ASD participants combining behavioral tasks with
neuroimaging methods and transcranial brain stimulation as well as computational
modeling can help validate and complement this suggested model. Moreover, we
propose applying the behavioral paradigms, and the neurophysiological markers
mentioned in this review article for evaluating psychiatric treatment approaches
in ASDs. The investigation of modulating effects of different treatment
approaches on the neurophysiological markers of the MNS can help find specific
subgroups of ASDs patients and support tailored psychiatric interventions.
PMID- 29963754
TI - Call for Nominations, 2019 Jellinek Memorial Award.
PMID- 29963755
TI - Soy-Derived Phytochemical Genistein Modifies Chromatome Topology to Restrict
Cancer Cell Proliferation.
AB - Epidemiological data indicate that human cancer risk is significantly reduced by
the consumption of soy-based foods containing the "phytoestrogen" genistein,
which can signal via host cell estrogen receptors. While additional
chemoprotective effects of genistein induced by epigenetic factors have also been
reported, the key molecules and mechanisms involved are poorly defined. We
therefore investigated genistein effects on chromatin-bound proteins in the
estrogen receptor-deficient cell line MDA-MB-231 which is insensitive to
phytoestrogen signaling. After exposure to low-dose genistein for >1 month, MDA
MB-231 cells exhibited stable epigenetic alterations that are analyzed via
partial MNase digestion and TMT-based quantitative proteomics. 3177 chromatin
bound proteins are identified with high confidence, including 882 molecules that
displayed altered binding topology after cell conditioning with genistein.
Prolonged phytochemical exposure conferred heritable changes in the binding
topology of key epigenetic regulators including ATRX, SUV39H1/H2, and HP1BP3 that
are preserved in untreated progeny, resulting in sustained downregulation of
proliferation genes and reduced cell growth. These data indicate that soy
derivative genistein exerts complex estrogen receptor-independent effects on the
epigenome likely to influence tumorigenesis by restricting cell growth.
PMID- 29963756
TI - Deliberate clinical inertia: Using meta-cognition to improve decision-making.
AB - Deliberate clinical inertia is the art of doing nothing as a positive response.
To be able to apply this concept, individual clinicians need to specifically
focus on their clinical decision-making. The skill of solving problems and making
optimal clinical decisions requires more attention in medical training and should
play a more prominent part of the medical curriculum. This paper provides
suggestions on how this may be achieved. Strategies to mitigate common biases are
outlined, with an emphasis on reversing a 'more is better' culture towards more
temperate, critical thinking. To incorporate such an approach in medical
curricula and in clinical practice, institutional endorsement and support is
required.
PMID- 29963757
TI - Thoracoscopic resection for mediastinal thymolipoma in a child.
AB - Thymolipoma is a rare disease among benign tumors. We herein report the case of a
child who underwent thoracoscopic resection of a large thymolipoma. A 3-year-old
boy was diagnosed with an anterior mediastinal solid tumor. Thoracic imaging
revealed a fat density mass that was 8.0 * 5.0 * 3.5 cm in size. Given the MRI
findings of the tumor, we suspected that the lesion was a teratoma. We decided to
perform thoracoscopic exploration and, if possible, resection of the solid tumor
sequentially. We successfully resected the tumor thoracoscopically. A
histological examination revealed thymolipoma. For large mediastinal tumors in
the intrathoracic space in children, the thoracoscopic approach is recommended
when the tumor is preoperatively considered to be benign and resectable.
PMID- 29963758
TI - Diversity of Secondary Metabolites in the Liverwort Syzygiella rubricaulis (Nees)
Stephani (Jamesoniellaceae, Marchantiophyta) from Neotropical High Mountains.
AB - In order to evaluate the chemical diversity of Syzygiella rubricaulis (Nees)
Stephani, a species with a disjunct distribution in the neotropical high
mountains, a phytochemical study was carried out with samples from 12 different
populations of different altitudes from four South American countries. The
chemical profiles of lipophilic extracts were analyzed by GC/MS for each
population and 50 different compounds were found with the predominance and
richness of sesquiterpenes. The majority of the compounds were found only in one
population and the total number of substances ranged from 1 to 15 among the
populations, but these numbers were not correlated with altitude, and
characterize each population as distinct, based on similarity analysis. The
qualitative and quantitative variations of metabolites found are a response to
different conditions, under which they live, mostly likely altitudinal
conditions. Further studies on the quantification of these chemicals may provide
information on their ecological roles and importance for the distribution of S.
rubricaulis at different altitudes. Despite the known richness of secondary
metabolites produced by bryophytes, they are still poorly explored in the context
of the ecological expressions.
PMID- 29963759
TI - Cirrhosis affects maximal oxygen consumption, functional capacity, quality of
life in patients with hepatitis C.
AB - OBJECTIVE: The aim is assess, compare, and correlate maximal oxygen consumption
(VO2max. ), functional capacity and quality of life in cirrhotic patients with
hepatitis C virus (HCV) and in healthy individuals. METHODS: This case-control
study included 36 participants (18 patients with HCV cirrhosis and 18 healthy
individuals) matched for sex and age. VO2max was assessed using ergospirometry
with an incremental load test on a cycloergometer. Functional capacity was
measured by a 6-min walk test (6WT), and quality of life was assessed using the
36-Item Short-Form Health Survey (SF-36). RESULTS: Both the cirrhotic group and
the control group had similar results for sex (44.4% male) and age (55.6 +/- 8.31
and 55.2 +/- 8.85 years, respectively). The cirrhotic group scored lower in all
domains of the SF-36, on the VO2max test (cirrhotic group 16.2 [11.6-18.6]
ml/kg/min; control group 19.9 [16.28-26.9]; p = 0.007) and on the 6WT (cirrhotic
group 521.5 [476.25-544.75] m; control group 618.0 [570.75-643.75] m; p =
0.0001). Correlations were found between the 6WT and the VO2max (r = 0.801, p <
0.0001) and between the 6WT and quality of life (SF-361-functional capacity
domain; r = 0.552, p = 0.018) only in the cirrhotic group. CONCLUSION: Patients
with cirrhosis due to HCV show changes in VO2max and in functional capacity,
which have a significant impact on their quality of life.
PMID- 29963760
TI - Pilot study of combined FDG-PET and dynamic contrast-enhanced CT of locally
advanced cervical carcinoma before and during concurrent chemoradiotherapy
suggests association between changes in tumor blood volume and treatment
response.
AB - Modern PET/CT radiotherapy simulators offer FDG-PET and dynamic contrast-enhanced
(DCE) CT imaging for combined volumetric assessment of tumor metabolism and
perfusion. However, the clinical utility of such assessment has not been clearly
defined. Thus, in a prospective longitudinal study of primary cervical tumors
treated with concurrent chemoradiotherapy (CCRT) we evaluated: (1) whether PET
and perfusion parameters correlate or provide complementary information; (2) what
imaging changes occur during CCRT; and (3) whether any parameters are predictive
of treatment response as assessed by PET/CT 3 months posttherapy. FDG-PET/CT and
DCE-CT scans were performed on 21 patients prior to and during CCRT. Coregistered
volumetric parametric maps of standardized uptake value (SUV) measures and
perfusion parameters blood flow (BF), blood volume (BV), and permeability were
generated. Summary statistics for these parameters and their changes were
calculated within the metabolic tumor volume (MTV). Correlations between SUV and
BF/BV/permeability on local and global bases were assessed with Pearson's
coefficient r. MTV, maximum SUV, and mean SUV decreased significantly between the
pre- and during-treatment time points, while mean BV and permeability increased
significantly. Global correlations between mean BF/BV/permeability and mean SUV
values (-.15 < r < .29) were at most moderate. An increase in mean tumor BV
during treatment was significantly correlated with complete metabolic response on
3-month posttreatment PET/CT. Weak correlations of SUV and perfusion parameters
suggest a complementary role of FDG-PET and DCE-CT for tumor characterization.
The association between relative change in mean BV and outcome suggests a
potential role for DCE-CT in early evaluation of cervical tumor response to
chemoradiotherapy.
PMID- 29963761
TI - The Vitamin K Epoxide Reductase Vkorc1l1 Promotes Preadipocyte Differentiation in
Mice.
AB - OBJECTIVE: Identification of novel regulators involved in adipose development is
important to understand the molecular mechanism underlying obesity and associated
metabolic disorders. Through isolation and analysis of a vitamin K epoxide
reductase Vkorc1l1 mutant, this study aimed to disclose its function and
underlying mechanism in adipose development and to obtain valuable insights
regarding the mechanism of obesity. METHODS: A Vkorc1l1 mutation recovered from a
forward genetic screen for obesity-related loci in mice was characterized to
explore its effects in gene expression, animal metabolism, and adipose
development. Adipogenesis was evaluated in both Vkorc1l1 mutant stromal vascular
fraction and Vkorc1l1 knockdown preadipocytes. Intracellular vitamin K2 level and
the effect of vitamin K2 on adipogenesis were tested in primary preadipocytes.
RESULTS: Vkorc1l1 mutants displayed a considerably lower fat to body weight
ratio, substantially decreased plasma leptin, and significantly underdeveloped
white adipose tissue. Adipogenic defects related with Vkorc1l1 deficiency were
observed both in vivo and in vitro. Vitamin K2 could inhibit adipogenesis in
stromal vascular fraction. Increased intracellular vitamin K2 level was detected
in Vkorc1l1 mutant preadipocytes. CONCLUSIONS: Vkorc1l1 promotes adipogenesis and
possibly obesity. Downregulation of Vkorc1l1 increases intracellular vitamin K2
level and impedes preadipocyte differentiation.
PMID- 29963762
TI - Prevalence and risk factors for bluetongue in the State of Sao Paulo, Brazil.
AB - Bluetongue (BT), caused by Bluetongue virus (BTV), is a disease that affects
ruminants such as cattle, sheep, goats and deer. BTV is transmitted by female
midges of the genus Culicoides. In Brazil, information on the prevalence of BTV
in cattle is limited, so the objective of this work was to identify BTV serotypes
in cattle. The State of Sao Paulo was divided into seven cattle-producing
regions, and in each of them, 300 cattle farms were randomly selected. One animal
from each farm (out of a total of 1,598 farms) was selected and its sera tested
by virus neutralization technique against BTV serotypes (1-24 and 26) for
determining antibody titre. Moreover, for each sampled farm, an epidemiological
questionnaire was submitted to verify the type of cattle production and the
zootechnical and sanitary practices carried out, which could be associated with a
higher risk of BTV infection. In this study, antibodies (percentage, [95%
confidence interval]) were identified against 11 serotypes: BTV-1 (22.15%, [15.72
27.92]), BTV-2 (31.03%, [26.65-37.98]), BTV-3 (18.96%, [12.42-24.90]), BTV-4
(24.90% [19.41-29.12]), BTV-9 (6.82%, [1.45-11.72]), BTV-12 (7.50%, [2.82
12.51]), BTV-17 (23.90%, [17.35-29.35]), BTV-19 (10.20%, [4.62-5.56]), BTV-21
(30.66%, [25.00-36.00]), BTV-22 (12.14%, [5.91-18.55]), BTV-26 (57.00%, [51.41
63.59]). In this study, for the first time in Brazil serological evidence of the
presence of serotypes BTV-2, BTV-9, BTV-21 and BTV-26 is reported. The variable
'new cattle entering herd' was considered a risk factor for the occurrence of
infection (OR = 2.183, 95% CI = 1.6-2.9).
PMID- 29963763
TI - Axially Chiral Dibenzazepinones by a Palladium(0)-Catalyzed Atropo
enantioselective C-H Arylation.
AB - Atropo-enantioselective C-H functionalization reactions are largely limited to
the dynamic kinetic resolution of biaryl substrates through the introduction of
steric bulk proximal to the axis of chirality. Reported herein is a highly atropo
enantioselective palladium(0)-catalyzed methodology that forges the axis of
chirality during the C-H functionalization process, enabling the synthesis of
axially chiral dibenzazepinones. Computational investigations support
experimentally determined racemization barriers, while also indicating C-H
functionalization proceeds by an enantio-determining CMD to yield
configurationally stable eight-membered palladacycles.
PMID- 29963764
TI - Four-directional approach to the meso-transverse attachment combined with
preoperative radiological vascular simulation facilitates short-term surgical
outcomes in laparoscopic transverse colon cancer surgery.
AB - INTRODUCTION: Transverse colon resection is one of the most difficult
laparoscopic procedures because of anatomic hazards such as variations in the
mesenteric vascular anatomy and the complex structure of organs and surrounding
membranes. METHODS: We evaluated the short-term surgical outcomes of laparoscopic
transverse colon resection using a creative approach. This approach included
preoperative surgical simulation using virtual surgical anatomy by CT, a four
directional approach to the mesentery, and 3-D imaging during laparoscopic
surgery. RESULTS: A total of 45 consecutive patients who underwent laparoscopic
resection for transverse colon cancer from June 2013 to December 2017 were
enrolled in this study. All procedures were completed safely, with minor
postoperative complications, including two patients with anastomotic stenosis,
two with intra-abdominal phlegmon, one with delayed gastric emptying, and one
with pneumonia, all treated non-operatively. There were no conversions to open
resection. Operation time was 203 min (range, 125-322 min), and the estimated
blood loss during surgery was 5 mL (range, 0-370 mL). The mean postoperative
hospital stay was 10 days (range, 7-21 days), and no patients required
readmission. CONCLUSION: Short-term surgical outcomes after laparoscopic
transverse colon resection demonstrated that this creative approach was safe and
feasible. The four-directional approach to the meso-transverse attachment
combined with preoperative radiological simulation can facilitate laparoscopic
transverse colon surgery.
PMID- 29963765
TI - Correlation between negative expression of pepsinogen C and a series of
phenotypic markers of gastric cancer in different gastric diseases.
AB - Gastric tumorigenesis is a multistep process initiated by chronic superficial
gastritis (SG), followed by atrophic gastritis (AG), then intestinal metaplasia
(IM), and finally by dysplasia and adenocarcinoma according to the Correa model.
Pepsinogen C (PGC) decreases gradually during progression of cancer, which makes
PGC an ideal negative marker for GC. To explore the correlation between PGC and
other positive tumor markers in different gastric diseases, we observed the
expression of PGC, MG7-Ag, MMP9, NM23, Ki-67, and E-cadherin by
immunohistochemistry, quantitative RT-PCR, and immunoblot analysis. Our results
showed that in SG, PGC was highly expressed while malignant phenotype markers
were rarely expressed. In contrast with SG, malignant phenotype markers were
highly expressed while the positive rate of PGC reached only 1.44% in GC. So
there was no coexpression of PGC and malignant phenotype markers in SG or GC
tissues. Only in the AG group, which is well-known to be gastric precancerous
disease, coexpression of PGC and malignant phenotype markers was detected. Our
results suggested that the expression of PGC in AG was negatively correlated with
that of MG7-Ag and MMP9. Of all AG, those with low expression of PGC and high
expression of MG7-Ag and MMP9 may possess a greater potential of malignant
transformation. Combined detection of negative marker PGC and positive markers
MG7-Ag and MMP9 could be used as a potential follow-up panel for monitoring
dynamical progression of AG and improving the detection efficiency of high-risk
individuals of gastric cancer, and then taking necessary interventions on the
target population.
PMID- 29963766
TI - Using behavioural insights to increase HIV self-sampling kit returns: a
randomized controlled text message trial to improve England's HIV self-sampling
service.
AB - OBJECTIVES: The aim of the study was to determine whether behaviourally informed
short message service (SMS) primer and reminder messages could increase the
return rate of HIV self-sampling kits ordered online. METHODS: The study was a 2
* 2 factorial design randomized control trial. A total of 9585 individuals who
ordered a self-sampling kit from www.freetesting.hiv different SMS combinations:
1) standard reminders sent days 3 and 7 after dispatch (control); 2) primer sent
1 day after dispatch plus standard reminders; 3) behavioural insights (BI)
reminders (no primer); or 4) primer plus BI reminders. The analysis was
restricted to individuals who received all messages (n = 8999). We used logistic
regression to investigate independent effects of the primer and BI reminders and
their interaction. We explored the impact of sociodemographic characteristics on
kit return as a secondary analysis. RESULTS: Those who received the primer and BI
reminders had a return rate 4% higher than that of those who received the
standard messages. We found strong evidence of a positive effect of the BI
reminders (odds ratio 1.13; 95% confidence interval 1.04-1.23; P = 0.003) but no
evidence for an effect of the primer, or for an interaction between the two
interventions. Odds of kit return increased with age, with those aged >= 65 years
being almost 2.5 times more likely to return the kit than those aged 25-34 years.
Men who have sex with men were 1.5-4.5 times more likely to return the kit
compared with other sexual behaviour and gender identity groups. Non-African
black clients were 25% less likely to return the kit compared with other
ethnicities. CONCLUSIONS: Adding BI to reminder messages was successful in
improving return rates at no additional cost.
PMID- 29963767
TI - Ternary deep eutectic solvent magnetic molecularly imprinted polymers for the
dispersive magnetic solid-phase microextraction of green tea.
AB - Ternary deep eutectic solvent magnetic molecularly imprinted polymers grafted on
silica were developed for the selective recognition and separation of
theophylline, theobromine, (+)-catechin hydrate, and caffeic acid from green tea
through dispersive magnetic solid-phase microextraction. A new ternary deep
eutectic solvent was adopted as a functional monomer. The materials obtained were
characterized by FTIR spectroscopy, field emission scanning electron microscopy,
transmission electron microscopy, NMR spectroscopy, and powder X-ray diffraction.
The practical recovery of the theophylline, theobromine, (+)-catechin hydrate,
and caffeic acid isolated with ternary deep eutectic solvent magnetic molecularly
imprinted polymers in green tea were 91.82, 92.13, 89.96, and 90.73%,
respectively, and the actual amounts extracted were 5.82, 4.32, 18.36, and 3.69
mg/g, respectively. The new method involving the novel material coupled with
dispersive magnetic solid-phase microextraction showed outstanding recognition,
selectivity and excellent magnetism, providing a new perspective for the
separation of bioactive compounds.
PMID- 29963768
TI - Iron(II)-Polypyridyl Complexes Inhibit the Growth of Glioblastoma Tumor and
Enhance TRAIL-Induced Cell Apoptosis.
AB - A promising cancer-targeting agent for the induction of apoptosis in tumor
necrosis factor (TNF) proteins, the TNF-related apoptosis-inducing ligand (TRAIL)
ligand, has found limited applications in the treatment of cancer cells, owing to
its resistance by cancer cell lines. Therefore, the rational design of anticancer
agents that could sensitize cancer cells towards TRAIL is of great significance.
Herein, we report that synthetic iron(II)-polypyridyl complexes are capable of
inhibiting the proliferation of glioblastoma cancer cells and efficiently
enhancing TRAIL-induced cell apoptosis. Mechanistic studies demonstrated that the
synthesized complexes induced cancer-cell apoptosis through triggering the
activation of p38 and p53 and inhibiting the activation of ERK. Moreover, uPA and
MMP-2/MMP-9, among the most important metastatic regulatory proteins, were also
found to be significantly alerted after the treatment. Furthermore, we also found
that tumor growth in nude mice was significantly inhibited by iron complex Fe2
through the induction of apoptosis without clear systematic toxicity, as
indicated by histological analysis. Taken together, this study provides evidence
for the further development of metal-based anticancer agents and chemosensitizers
of TRAIL for the treatment of human glioblastoma cancer cells.
PMID- 29963769
TI - Evaluation of CHK1 activation in vulvar squamous cell carcinoma and its potential
as a therapeutic target in vitro.
AB - CHK1 is an important regulator of the cell cycle and DNA damage response, and its
altered expression has been identified in various tumors. Chk1 inhibitors are
currently being evaluated as monotherapy and as potentiators of chemotherapy in
clinical settings. However, to our knowledge, no previous study has investigated
either the activation status or the therapeutic potential of CHK1 targeting in
vulvar cancer. Therefore, we examined the expression status of activated CHK1
forms pCHK1Ser345 , pCHK1Ser317 , pCHK1Ser296 , and pCHK1Ser280 in 294 vulvar
squamous cell carcinomas (VSCC) using immunohistochemistry and analyzed their
relationships with various clinicopathological variables and clinical outcome. To
aid translation of preclinical studies, we also assessed cell sensitivity to the
Chk1 inhibition in two vulvar cancer cell lines. Compared to the levels of
pCHK1Ser345 , pCHK1Ser317 , pCHK1Ser296 , and pCHK1Ser280 in normal vulvar
squamous epithelium, high nuclear pCHK1Ser345 expression was found in 57% of
vulvar carcinomas, whereas low nuclear pCHK1Ser317 , pCHK1Ser296 , and
pCHK1Ser280 expressions were observed in 58%, 64%, and 40% of the cases,
respectively. Low levels of pCHK1Ser317 and pCHK1Ser280 in the nucleus correlated
significantly with advanced tumor behaviors and aggressive features. None of
pCHK1Ser345 , pCHK1Ser317 , pCHK1Ser296 , and pCHK1Ser280 forms were identified
as prognostic factors. In vitro inhibition of CHK1 by small molecular inhibitors
or siRNA reduced viability by inducing DNA damage and apoptosis of vulvar cancer
cell lines. In summary, we conclude that cellular functions regulated by CHK1 are
phosphorylation/localization-dependent and deregulation of CHK1 function occurs
in VSCC and might contribute to tumorigenesis. Targeting CHK1 might represent as
a useful antitumor strategy for the subgroup of VSCC harboring p53 mutations.
PMID- 29963770
TI - Green Chemistry in Higher Education: State of the Art, Challenges, and Future
Trends.
AB - Nowadays, there is increasing interest in global sustainability, and thus,
university students would like to know how human actions affect the health status
of our planet. This is mainly due to their basic knowledge of problems such as
global warming and greenhouse gases. Students would like to gain knowledge on how
to safeguard the earth for future generations. This must involve changes in
education programs at interested institutions and universities. To ensure that
future generations of chemists are equipped with proper knowledge, significant
efforts are needed. Thus, this article aims to present the history of green
chemistry, its milestones, and ideas on how to teach this subject. A discussion
of awareness in the field of green chemistry and of existing teaching materials
is presented. In addition, green chemistry metrics, which should be known and
used by professors and students, are described. Teaching methods for green
chemistry are also given, with special attention paid to organic and analytical
chemistry education.
PMID- 29963771
TI - Antibody Profiling by Proteome Microarray with Multiplex Isotype Detection
Reveals Overlap between Human and Aotus nancymaae Controlled Malaria Infections.
PMID- 29963772
TI - Proteomic characterization of a selenium-metabolizing probiotic Lactobacillus
reuteri Lb2 BM for nutraceutical applications.
PMID- 29963773
TI - Enhanced recovery for elective colorectal surgery: from safety bundles to package
deals.
PMID- 29963774
TI - Is a transanal total mesorectal excision programme feasible in a single-team
setting?
PMID- 29963779
TI - Report of the ACPGBI President.
PMID- 29963781
TI - Reduction in glucose fluctuations in elderly patients with type 2 diabetes using
repaglinide: A randomized controlled trial of repaglinide vs sulfonylurea.
AB - AIMS/INTRODUCTION: Glinides are antidiabetic drugs that enhance the early phase
of insulin secretion, but have been considered to be less effective at lowering
blood glucose than sulfonylureas. However, glinides show a lower risk of
hypoglycemia and a greater effect on postprandial hyperglycemia, and are
particularly recommended for use in elderly patients with type 2 diabetes. We
investigated the efficacy and safety of repaglinide compared with sulfonylurea
for the treatment of elderly patients. MATERIALS AND METHODS: In the present
multicenter, prospective, randomized, open-label, controlled trial, 57 elderly
lean patients with type 2 diabetes who were being treated with sulfonylureas were
studied. They were either switched to repaglinide (Repa group) or continued a
sulfonylurea (SU group) for 12 weeks. The primary outcome comprised the change in
glycemic control, and among the secondary outcomes was the presence of
hypoglycemia and drug compliance. RESULTS: Although glycated hemoglobin (HbA1c)
was not significantly different between the two groups (SU +0.02% vs Repa
0.07%), greater improvements in the glycated albumin (GA) and GA to HbA1c ratio
(GA/HbA1c) were observed in the Repa group (DeltaGA, SU +0.12% vs Repa -1.15%;
DeltaGA/HbA1c, SU +0.01 vs Repa -0.13; each P < 0.01) without increasing
hypoglycemia. When the Repa group was subdivided according to whether GA
improved, the SU dose before switching to repaglinide was significantly smaller
and the homeostatic model assessment of beta-cell function was significantly
higher in the GA improvement subgroup. CONCLUSIONS: Switching from SU to Repa
improved GA and GA/HbA1c, and had favorable effects on glucose fluctuation in
elderly patients with type 2 diabetes.
PMID- 29963782
TI - Quantitative anatomy of the liver visceral surface in the human fetus.
AB - BACKGROUND: Understanding liver growth is relevant in both determining the status
of normative fetal development and prenatal detection of its disorders.
OBJECTIVES: This study attempted to examine age-specific reference intervals and
the best-fit growth dynamics of the liver visceral surface for hepatic height,
length, isthmic diameter, oblique diameters, circumferences of individual lobes,
and total liver circumference. MATERIAL AND METHODS: Using anatomical, digital
and statistical methods, the liver visceral surface was measured in 69 human
fetuses of both sexes (32 males and 37 females) aged 18-30 weeks, derived from
spontaneous abortions and stillbirths. RESULTS: The statistical analysis showed
no sex differences. The best growth models mostly followed natural logarithmic
functions, except for the length of the fissure for ligamentum teres hepatis and
the length of fossa for gallbladder, which increased commensurately. Neither the
length of fissure for ductus venosus nor the length of sulcus for inferior vena
cava modeled the best-fit curves. The vertical-to-transverse diameter ratio of
the liver was constant and averaged 0.75 +/-0.12, while the isthmus ratio
significantly altered from 0.78 +/-0.07 at 18-19 weeks through 0.68 +/-0.05 at 26
27 weeks to 0.72 +/-0.07 at 28-30 weeks of gestation. CONCLUSIONS: With no sexual
differences, the liver morphometric parameters increased either logarithmically
(lengths of: transverse diameter, vertical diameter, right oblique diameter, left
oblique diameter, isthmic diameter and porta hepatis, circumferences of: right
lobe, left lobe, quadrate lobe, caudate lobe, and total liver circumference) or
proportionately (length of fissure for ligamentum teres hepatis, length of fossa
for gallbladder). The quantitative data of the growing liver may be relevant in
both the ultrasound monitoring of fetuses and early detection of congenital liver
anomalies.
PMID- 29963783
TI - Migration of human mesenchymal stem cells stimulated with pulsed electric field
and the dynamics of the cell surface glycosylation.
AB - BACKGROUND: The analysis of the stem cells' glycome dynamics at different stages
of differentiation and migration makes possible the exploration of the cell
surface glycans as markers of the stem cell functional status, and, in the
future, compatibility between transplanted cell and host environment. OBJECTIVES:
The objective of our study was to develop novel techniques of investigating cell
motility and to assess whether the electric field of the therapeutic spinal cord
stimulation system used in vivo contributes to the migration of human mesenchymal
stem cells (hMSCs) in vitro. MATERIAL AND METHODS: We have investigated the
electrotaxis of bone marrow-derived MSCs using pulsed electric field (PEF) in the
range of 16-80 mV/mm and the frequency of 130 Hz and 240 Hz. The PEF-related
dynamics of the cell surface glycosylation was evaluated using 6 plant lectins
recognizing individual glycans. RESULTS: Pulsed electric field at physiological
levels (10 mV/mm; 130 Hz) did not influence cellular motility in vitro, which may
correspond to the maintenance of the transplanted cells at the lesion site in
vivo. An increase of the PEF intensity and the frequency exceeding physiological
levels resulted in an increase in the cellular migration rate in vitro. Pulsed
electric field elevated above physiological intensity and frequency (40-80 mV/mm;
240 Hz), but not at physiological levels, resulted in changes of the cell surface
glycosylation. CONCLUSIONS: We found the described approach convenient for
investigations and for the in vitro modeling of the cellular systems intended for
the regenerative cell transplantations in vivo. Probing cell surface glycomes may
provide valuable biomarkers to assess the competence of transplanted cells.
PMID- 29963784
TI - Potential plasma biomarkers of bladder cancer identified by proteomic analysis: A
pilot study.
AB - BACKGROUND: Bladder cancer diagnosis and surveillance includes cystoscopy and
cytology. New methods for the detection of bladder cancer are needed, because
cystoscopy is invasive and expensive, and because urine cytology is not sensitive
enough. OBJECTIVES: The aim of the study was to select potential plasma protein
markers for bladder cancer which could be useful in developing a specific
laboratory test to improve diagnosis and to establish treatment strategies in
order to prevent the recurrence of the disease. MATERIAL AND METHODS: Plasma
proteome maps were prepared based on 2-dimensional sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE), combined with image gel analysis
and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
spectrometry of plasma samples from patients with urothelial bladder cancer, and
they were compared to normal samples. RESULTS: The analyses of bladder cancer
plasma samples allowed us to distinguish 3 groups of proteins whose relative
abundance differed from that in normal samples. The 1st one comprised modified
forms of plasma transferrin, fibrinogen gamma and complement C3b, which were
absent in normal plasma. The 2nd group comprised haptoglobin, alpha-2
macroglobulin, vitamin D-binding protein, and pigment epithelium-derived factor,
which occurred in the cancerous samples in large quantities. The 3rd group
consisted of 3 molecular forms of immunoglobulin M (IgM), the relative abundance
of which was significantly lower in the cancerous plasma samples. CONCLUSIONS:
The data indicated potential plasma biomarkers associated with inflammation,
immunity and coagulation processes accompanying bladder cancer. They could be
used for the development of a laboratory test(s) useful in clinical practice.
PMID- 29963780
TI - Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver
transplant recipients who experience recurrence of hepatitis C: A prospective
nationwide cohort study.
AB - Direct-acting antivirals have proved to be highly efficacious and safe in
monoinfected liver transplant (LT) recipients who experience recurrence of
hepatitis C virus (HCV) infection. However, there is a lack of data on
effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients
who experience recurrence of HCV infection after LT. In this prospective,
multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who
received DAA therapy (with or without ribavirin [RBV]) were compared with those
of a matched cohort of 148 HCV-monoinfected LT recipients who received similar
treatment. Baseline characteristics were similar in both groups. HCV/HIV
coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467)
cells/uL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens
administered were SOF + LDV +/- RBV (34%), SOF + SMV +/- RBV (31%), SOF + DCV +/-
RBV (27%), SMV + DCV +/- RBV (5%), and 3D (3%), with no differences between the
groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum
HCV-RNA at 12 weeks after the end of treatment) were high and similar for
coinfected and monoinfected patients (95% and 94%, respectively; P = .239).
Albeit not significant, a trend toward lower SVR rates among patients with
advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In
conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV
infection in HIV-infected individuals were highly effective and well tolerated,
with results comparable to those of HCV-monoinfected patients.
PMID- 29963785
TI - Clinical and nutritional correlations in Parkinson's disease: Preliminary report.
AB - BACKGROUND: Parkinson's disease (PD) is one of the most common neurodegenerative
disorders. Malnutrition is an essential problem in the late stage of PD. Lowering
of body mass is seen in 30% of patients, and malnutrition or the risk of
malnutrition in 24% and 60%, respectively. OBJECTIVES: The aim of the study was
an analysis of the relationships between the parameters of the nutritional stage
and the advancement of clinical symptoms in PD patients. MATERIAL AND METHODS: A
total of 40 patients (18 men, 22 women) with PD were analyzed, mean age: 70.7
years. In all patients, structured anamnesis, Nutrition Risk Screening (NRS
2002), body mass index (BMI), morphology, and basic biochemical tests were
conducted. Skin fold thickness was also measured. The results were referred to
the score of different scales. RESULTS: The study showed a lot of correlations
between the severity of PD, mostly motor symptoms in the Unified Parkinson's
Disease Rating Scale (UPDRS), and parameters characterizing the patient's
nutritional status. We revealed a correlation between malnutrition and PD
duration, and l-DOPA frequency intake. The global score of parts I, II and III of
UPDRS were correlated with the nutritional status. The results confirmed the
existence of more severe smell change and taste impairment in the late stage of
PD, with more pronounced malnutrition. CONCLUSIONS: The duration of PD, motor and
non-motor PD symptoms, and the frequency of l-DOPA intake closely correlate with
the nutritional status. Understanding of the multifactorial interdependence might
be useful in the estimation of the algorithm for monitoring the nutritional
status of PD patients and taking early nutritional intervention.
PMID- 29963786
TI - The importance of the Wnt/beta-catenin pathway and LRP5 protein in bone
metabolism of postmenopausal women.
AB - BACKGROUND: Postmenopausal osteoporosis is the most common metabolic bone disease
among women. The Wnt signaling pathway has been known to be the critical
regulator of osteoblastogenesis. Alterations in this mechanism may have
consequences for bone remodeling in humans. OBJECTIVES: The aim of the study was
to evaluate the frequency of genotypes and alleles of single nucleotide
polymorphism (SNP) rs4988321 and rs312009 of LRP5 in Polish postmenopausal women
with osteopenia (n = 109) and osteoporosis (n = 333). Potential correlations
between genetic polymorphisms, bone mineral density (BMD), risk for bone
fractures, and other clinical parameters were analyzed. MATERIAL AND METHODS:
Genomic DNA was extracted from the blood samples and the sequence polymorphisms
of LRP5 gene were detected using real-time polymerase chain reaction (RT-PCR)
methods with melting curve analysis. We also calculated the odds ratio (OR) for
the LRP5 genotypes and the alleles. Then, we evaluated the effect of the LRP5
polymorphism on T-score, Z-score, L2L4AM, L2L4YA, L2L4BMD, body mass index (BMI),
and other clinical parameters. RESULTS: No statistically significant differences
in the distribution of LRP5 rs312009 genotypes between the groups were observed.
Furthermore, our findings indicate that there is no correlation between LRP5
genotypes and the clinical characteristics of women with osteopenia/osteoporosis.
In contrast, there was an increased value of OR in heterozygotes for rs4988321,
both in patients with osteopenia (OR = 1.47) and in those with osteoporosis (OR =
1.33). In our study, we were not able to calculate the OR parameter for the AA
genotype due to its low prevalence in the population. CONCLUSIONS: Our results
suggest that the Val667Met LRP5 (rs312009) polymorphism may contribute to an
elevated risk for fractures in postmenopausal Polish women.
PMID- 29963787
TI - Cognitive impairment, event-related potentials and immunological status in
patients with systemic lupus erythematosus.
AB - BACKGROUND: Cognitive impairment (CI) is a frequent problem in lupus patients,
regardless of their overt neuropsychiatric (NP) involvement. OBJECTIVES: The aim
of our study was to test cognitive abilities in systemic lupus erythematosus
(SLE) patients by means of neuropsychological testing and event-related
potentials (ERPs), and to search for their cognitive abilities correlations with
a wide range of auto-antibodies. MATERIAL AND METHODS: A total of 37 SLE patients
were subjected to a battery of neuropsychological tests, recommended by the
American College of Rheumatology (ACR), and to ERPs. They were also tested for a
wide range of auto-antibodies (anti-cardiolipin (aCL), anti-beta2-glycoprotein I
(anti-beta2-GPI), lupus anticoagulant, anti-dsDNA, anti-nucleosome, anti
ribosomal P (anti-Rib-P), anti-ganglioside, anti-Ro/SS-A, and anti-La/SS-B.
RESULTS: Cognitive impairment was found in 35% of patients, mostly with NP SLE
(NPSLE), and was associated with higher disease activity, measured by the SLE
Disease Activity Index (SLEDAI), and with a longer duration of central nervous
system (CNS) involvement. There were no differences in the immunological status
between CI patients and those without cognitive decline, but some antibodies were
correlated with worse results in certain neuropsychological tests (anti-dsDNA and
worse results of Rey Complex Figure Test - RCFTc for copying and RCFTr for
recall, and of verbal fluency test (VFT); aCL IgG and worse results in Digit Span
(DS) and in RCFTc). Event-related potentials showed prolonged N200 and P300
latencies in SLE patients in comparison to controls, but no differences were
found between SLE and NPSLE patients. Mean P300 latency was significantly longer
in patients without anti-nucleosome antibodies. CONCLUSIONS: Event-related
potentials can be used as a complementary tool in assessing CI in SLE patients.
The immunological status of patients with CI did not differ from that of patients
without cognitive problems.
PMID- 29963788
TI - Presentation, diagnosis and treatment of colorectal cancer.
AB - Colorectal (bowel) cancer remains a common disease, particularly in developed
countries. If diagnosed early, it has a high five-year survival rate, yet the
disease remains a significant cause of mortality. This article aims to improve
nurses' understanding of the signs and symptoms of colorectal cancer, and the
role of all nurses in supporting early diagnosis and providing follow-up care. It
also discusses the available treatment options for colorectal cancer, enabling
nurses to offer informed care to patients, who in turn, can make informed
decisions about their treatment.
PMID- 29963789
TI - [Preparation,Identification,and Application of Monoclonal Antibody against Orf
Virus 118 Protein].
AB - This study was designed to prepare a monoclonal antibody against Orf virus 118
protein and explore the biological properties of ORFV118 using this antibody. We
constructed a recombinant plasmid pET33b-ORFV118 that contained a full-length
ORFV118 gene. The plasmid was transformed into E.coli BL21,and the expression of
ORFV118 was induced by isopropyl-beta-d-thiogalactoside (IPTG).Prokaryotic
ORFV118 was purified via Ni-NTA affinity chromatography and was subsequently used
as an antigen to immunize mice. An anti-ORFV118 antibody was prepared using
hybridoma technology. The titer and specificity of this antibody were tested by
an indirect ELISA and Western blot/immunohistochemistry, respectively. We
successfully obtained three antibody-secreting hybridomas,1A2,3B5,and 5D10.The
titers of the three hybridomas were 1:10000,1:6400,and 1:8000.The monoclonal
antibody (mAb),1A2 and the highest titer was selected for further research. The
mAb 1A2,an IgG1 type antibody was bonded to its immunizing antigen, both the
eukaryotic and natural ORFV118 with high specificity. The immunohistochemical
analysis showed that the focal specific staining was restricted to the epidermal
layer and subcutaneous tissue, which conformed to the characteristics of an ORFV
infection. The mAb 1A2 recognized ORFV118with high specificity. Further study of
mAb 1A2 will facilitate our understanding of ORFV118 and provide potentially
novel methods for the diagnosis, prevention, and treatment of Orf.
PMID- 29963790
TI - The main participation of the enterohormone GLP-1 after bariatric surgery.
AB - INTRODUCTION: Numerous hypotheses are called to explain the beneficial effect on
glucose metabolism after bariatric surgery. Some authors advocate for the
secretion and release of various substances with endocrine functions for the
explanation on this event. One of the substances most marked as effector, with
contrasting effects but controversial data is GLP-1. METHODS: Our study was
performed in healthy male Wistar rats, to avoid the absence of confounding
factors such as T2DM and obesity. In order to know the adaptation of GLP-1
secretion after surgery 5 groups were designated. Two control groups (fasting and
surgical stress), and three surgical groups (Gastric sleeve, 50% resection of the
midgut and the Roux en Y gastric bypass). After three months the GLP-1 synthesis
in the different portions of the small intestine and the expression of the
membrane receptors in pancreatic islet cells were studied by immunohistochemical
techniques. RESULTS: There was a significant increase in the number of secretory
cells in ileum, duodenum and jejunum in mixed (RYGB) and malabsorptive (RI50)
surgical groups. An elevation of pancreatic receptors signal was also observed in
the same techniques versus controls. CONCLUSIONS: Our data indicate that
intestinal secretion of GLP-1 and its sensitivity to the pancreatic changes were
increased like a response of an adaptive effect to the mechanical aggression of
the digestive tube and as alteration of nutrient flow after surgery.
PMID- 29963791
TI - Results following laparoscopic sleeve gastrectomy in elderly obese patients: a
single center experience with follow up at three years.
AB - BACKGROUND: Laparoscopic Sleeve Gastrectomy (LSG) represents the most performed
bariatric surgical procedure worldwide. Morbid Overweight in elderly patients is
becoming a significant health problem even in Italy. As well as in younger age
groups, bariatric surgery could be indicated even in this subset of patients.
However the advantages and results of LSG in patients over 60 years old have
received minimal attention. METHODS: The records of 375 patients underwent LSG
between 2008 and 2016 were reviewed. In the entire series 18 patients were aged
60 years or older at the time of surgery. Since a 3 years follow up was available
for 12 patients out of the 18 aged over 60 we included in the study only these.
General epidemiologic data, clinical findings, BMI and comorbidities surgical
treatment and follow-up data were collected; postoperative measurements such as
operative time, intraoperative complications, mortality rate, length of stay,
incidence of early and late complications, Body mass Index (BMI), excess weight
loss rate (EWL%) and comorbidities resolution were also recorded. RESULTS: LSG
was successfully performed for all geriatric patients. Global complications rate
was 16.6% At 3 years mean BMI was 34.4+/-3.8 with a mean EWL% 66.1+/-31.9.
Postoperative resolution of obesity comorbidities was observed; Hypertension
(71.4%), Type 2 Diabetes Mellitus (T2DM) (50.0%), Obstructive Sleep Apnea
Syndrome (OSAS) (66.6%) respectively. No intraoperative complications or
mortality were recorded. CONCLUSIONS: LSG offered cure in geriatric patients
affected by morbid obesity for weight loss and comorbidities resolution. Larger
studies are necessary to analyze and minimize the incidence of postoperative
complications associated to this surgical procedure in elderly patients.
PMID- 29963792
TI - Role of endosonography prior to endoscopic treatment of esophageal cancer.
AB - Esophageal cancer is a common disease with poor survival rates. The treatment and
prognosis of patients with esophageal cancer depend on the stage of the disease.
Accurate clinical staging is critical for stratifying patients for treatment.
While advanced cancers are generally treated by neoadjuvant chemoradiotherapy and
surgery, early cancers may be amendable to endoluminal, minimally invasive
treatments, thus saving patients from unnecessary surgery. Endoscopic
ultrasonography has a major role in loco-regional staging of esophageal cancer
and should be performed in all patients after excluding significant comorbidities
and distant metastases. However, the role of endosonography seems to be limited
in early cancer, since it does not determine the depth of invasion with
sufficient accuracy. This can prove decisive for treatment planning. Despite
substantial efforts, its main role in early cancer is still confined to ruling
out the deeper involvement or lymph node metastasis. A preferable treatment is
for patients to undergo a diagnostic endoscopic resection, which facilitates
correct pathological staging and final treatment decision.
PMID- 29963793
TI - [Molecular Identification and Variation Analysis of the NSP2 and ORF5 Genes of
PRRSV in Henan Province from 2014 to 2015].
AB - This study aimed at investigating the molecular epidemiology and genetic
variation of PRRSV based on the detection of 250 clinical samples collected from
118 farms from 2014 to 2015in different regions of Henan Province by RT-PCR. The
NSP2 and ORF5genes of the PRRSV-positive samples were sequenced and analyzed. The
results showed that 58 samples were positive for PRRSV, with a positive rate of
23.2%.A total of 29NSP2 and 31ORF5genes were obtained. The phylogenetic analysis
revealed that most of the prevalent strains belonged to the North American
genotype. Among the 58 positive samples,14 strains were highly homologous with HP
PRRSV, another 15 samples were highly homologous with the North American
prevalent strain, and NADC30 contained a discontinuous deletion of 131 amino
acids in Nsp2,which had been recently reported in China and Korea. This study
showed that the HP-PRRSV and NADC30-Like strains are presently the dominant
strains in Henan,particularly in comparison with the results from 2012 to
2013.Moreover,the NADC30-Like strains accounted for a higher percentage. In
addition, both the NSP2 and ORF5genes had significant variations, suggesting that
more attention should be continuously paid to monitor the pathogenic epidemiology
and genetic variation of PRRSV. Furthermore, additional research should be
conducted regarding the mechanism of pathogenicity and immunological suppression
of PRRSV to provide a reference for the research and development of vaccines and
antiviral drugs.
PMID- 29963794
TI - [Proinflammatory Cytokine and Chemokine Production of Mouse Macrophages in
Response to EV-A71 Infection].
AB - To study the replication and antiviral innate immunity of EV-A71 in mouse
macrophages, we selected the mouse macrophage RAW264.7cell line as a model. An
absolute quantitative PCR detection method was constructed to detect the viral
load of EV-A71 in RAW264.7cells.RT-qPCR detected the fold changes of the
proinflammatory cytokine, chemokine, and pattern recognition receptors at
different time points post-infection in RAW264.7cells infected with EV-A71 and UV
inactivated EV-A71.The results revealed that the viral load of EV-A71 in
RAW264.7cells decreased as the time post-infection increased. Proinflammatory
cytokines, including IL-1beta,IL-6,TNF-alpha,and chemokines, including IP-10,MCP
1,and MIP-1alphawere induced, and the mRNA expression levels of
TLR2,TLR1,TLR6,MDA5,and RIG-I were up-regulated. These results indicate that EV
A71 could replicate in mouse macrophages at a lower level, and proinflammatory
cytokine and chemokine responses were induced.
PMID- 29963795
TI - Microbiological profile of chronic suppurative otits media among HIV infected
children in South Eastern Nigeria.
AB - Background: Immune compromised HIV/AIDS infected children have consistently shown
a higher prevalence of chronic suppurative otitis media than their immune
competent counterparts.This study aimed to compare the microbial isolates from
ear discharges in HIV infected and non infected children. Method: This was a
Hospital based prospective cohort study designed to determine the relative
prevalence of the common organisms present in chronically discharging ears of HIV
infected children and their antimicrobial sensitivities and compare that of age
and sex matched non HIV infected children. Fifty HIV infected children being
followed up at the paediatric HIV clinic of a tertiary health facility, had ear
swabs obtained for culture and antimicrobial sensitivity.The same was done for
another cohort of fifty age and sex matched non HIV infected children. Results:
The mean age of the study population and controls were 6years 11months (SD 0.96)
and 7years 11 months (SD 1.00) respectively. Male to female ratio for each group
was 1:1.Ear discharge was bilateral in 27(54%) HIV infected children and in
35(70%) of the controls. The most prevalent bacterial isolate in both groups was
Pseudomonas aeruginosa though it was more prevalent in HIV infected
children(P=0.005). Fungal isolates were commoner in non HIV infected
children(P=0.001).Ninety percent sensitivity to the 4 Quinolones was recorded by
isolates in HIV infected children while sensitivity to the Aminoglycosides was
greater in non HIV infected children Conclusion: Pseudomonas aeruginosa is the
predominant organism isolated from HIV infected children with chronic otitis
media.Fungal isolates are less frequently encountered in ear discharges of HIV
infected children. The 4 Quinolones are the drugs of choice in treatment of
Chronic suppurative otitis media in HIV infected children.
PMID- 29963796
TI - Awareness and attitude towards HPV and its vaccines among market women in Bodija
Market, Ibadan.
AB - Background: Cervical cancer, commonest among cancers of the female genital tract
continued to pose major challenge to women of reproductive age in developing
countries though infection by its causative agent, human papilloma virus (HPV) is
preventable.This study aimed to assess awareness and attitude of market women
concerning HPV and its vaccines in prevention of cervical cancer. Materials and
Methods: A cross sectional study involving 329 market women, using multistage
sampling technique. Instrument was an Interviewer--administered questionnaire on
socio-demographic characteristics, knowledge and awareness of HPV and its
vaccine, sexual history and attitude towards HPV vaccines. Data analysis was done
using SPSS version 20.0 with statistical significance level set at p<0.05.
Results: Mean age of respondents was 29.49 +/- 3.65 years. All respondents were
sexually active with majority (94.8%) having multiple sexual partners. Awareness
of HPV vaccine and Pap smear test was among 1.2% and 9.4% respectively. Attitude
towards HPV vaccination was good in 304 (92.4%) with 302 (91.8%) willing to take
the HPV vaccines. There was significant association between attitude towards HPV
vaccine and willingness to take HPV vaccine x2=111.8, p<0.01). Conclusions:
Awareness of HPV and its vaccines is low among market women in our community.
Policies and actions to step up information dissemination are urgently needed in
order to stem the scourge of cervical cancer in our society.
PMID- 29963797
TI - Midterm results with drug-coated balloons for SFA lesions in patients with CLI:
comparison with conventional bypass surgery.
AB - BACKGROUND: Endovascular treatment of symptomatic peripheral artery disease has
gained widespread acceptance. The efficacy and safety of drug-coated balloon
(DCB) angioplasty in the setting of critical limb ischemia in comparison to
conventional surgery has not been demonstrated. We have compared our results with
DCB angioplasty to conventional bypass surgery in patients with critical limb
ischemia (CLI). METHODS: A total of 187 patients with CLI treated over a 6-year
period between 2006 and 2012 by a single operative team constituted the study
population. Between 2006 and 2009, all patients underwent conventional surgery.
Between 2009 and 2012, the investigators adopted endovascular approach with the
use of IN.PACT Admiral (Medtronic Inc., Santa Rosa, CA, USA). Data collection was
achieved prospectively. RESULTS: A total 210 procedures (100 surgery, 110
endovascular) were performed over a 6-year period. A 72% of all bypasses were
performed using saphenous vein grafts with above-the-knee bypass as the technique
of choice in 80% of the cases. 6-mm DCB was used in 41% of the patients.
Procedural success rates (98% vs. 99%, NS) as well as clinical success rates (99%
vs. 99%, P=NS) and operative mortality (3.7% vs. 2%, NS) was similar in both
groups. Primary patency for DCB vs. bypass groups 91.8% vs. 88.9%, respectively
(P=0.31) at 12 months and 82.7% vs. 82.8% at 24 months, respectively (P=0.28).
Freedom from clinically-driven target lesion revascularization at 12 months was
similar in both groups (87.6% vs. 85%, P=0.33). Primary patency for DCB vs.
bypass groups at 24 months was 82.7% vs. 82.8%, respectively (P=0.28).
CONCLUSIONS: DCB angioplasty yields comparable results to surgery in the setting
of critical ischemia. The efficacy and the safety of DCBs in more complex lesions
is to be investigated with randomized trials.
PMID- 29963798
TI - Soil transmitted helminth infection among farmers in Ukwa West Local Government
Area, Abia State, south-east, Nigeria.
AB - Background: Farmers like most groups of workers are faced with a multiplicity of
hazards and biological hazards like Soil Transmitted Helminths - a major Public
health problem in the tropical like Nigeria is one of them. This study was to
determine the prevalence of Soil-Transmitted Helminths (STHs) infections among
farmers in Ukwa West Local Government Area (LGA) of Abia State, South East
Nigeria. Methods: Following ethical clearance,290 consenting farmers were
recruited to participate in this descriptive cross sectional study. They
responded to pre-tested, structured, close ended interviewer administered
questionnaires which probed socio-demographics,knowledge and behaviour towards
STHs. Also, stool and blood samples were collected from participants and examined
for helminth ova and estimation of packed cell volume respectively. A Walk
Through Survey of the farms for immediate work place situation and safety was
carried out. Collected data were analysed using descriptive and analytical tools.
Results: There was a 33.1% prevalence of infection with STHs and a 67.6%
prevalence of anaemia among respondents. Hookworm had the highest (59.6%)
prevalence just as anaemia amongst farmers with STHs was higher than among
respondents who were not diagnosed with the disease. Knowledge of STHs and the
availability and use of personal protective equipment (PPEs) were poor.
Conclusion: There was a high prevalence of STHs among farmers in Ukwa West Local
Government Area of Abia State, South East Nigeria occasioned inter alia by the
behaviour and poor use of PPEs. Health Education, routine de-worming and use of
PPEs are recommended.
PMID- 29963799
TI - Close and positive margins in non-melanoma skin malignancies of the head and
neck. What to do in patients over 75 years of age? A preliminary study.
AB - BACKGROUND: The incidence of non-melanoma skin cancer (NMSC) of the head and neck
is increasing among older adults where it is credited to have a poorer prognosis
also because the radicality of the surgery is often missed for a too conservative
approach. An assessment of the amount of tumor regrowth and its prognostic
consequences, in patients with surgical margins close or involved and older than
75 years, seems thus worth to be pursued in order to provide the best therapeutic
strategy. METHODS: 91 cases of Basal Cell Carcinomas (BBC) and Squamous Cell
Carcinomas (SCC), in patients older than 75 years of age, were followed from a
minimum of one year to up to ten years. 15 patients had close margins at
histology while 30 patients turned out to have positive margins. The other 46
patients had clear histologic margins and were considered as a control group.
Several parameters were also taken into account like the site of occurrence,
morphology, grading, size, thickness, type of margin involved (lateral, deep or
both) and the status of the neck, for the SCC. A cut-off follow-up of two years
(less than two years and more than two years) was adopted. RESULTS: Among the
BCCs there was one recurrence in the clear margin subgroup (1/23 - 4.3 %) and two
in the positive margin subgroup (2/20 - 10 %). For the SCCs there was only one
recurrence in the group of positive margins (1/10 - 10%). Hence the observed rate
of recurrence was much lower than reported in the literature. CONCLUSIONS: In the
Authors' opinion the low tendency to recur that NMSC show in people older than 75
years might validate, at least in this age group, an "economic" surgical approach
and a watchful attitude. Larger numbers are needed to assess and possibly
validate this strategy, especially for the SCCs.
PMID- 29963800
TI - Tattoo cutaneous adverse reactions effectively treated with Q-switched Nd:YAG
laser.
PMID- 29963801
TI - Gianotti-Crosti syndrome and atypical hand-foot-mouth disease: two distinct
entities or two manifestation of the same infection?
PMID- 29963802
TI - Peculiar hypertrichosis in a patient affected by Frontal fibrosing alopecia with
pseudo "fringe sign".
PMID- 29963803
TI - The epidemiology of psoriasis in an Italian area: population-based analysis of
administrative data.
AB - BACKGROUND: Data on the epidemiology of psoriasis are limited.The objective of
this study was to estimate the prevalence and the incidence rate of psoriasis in
a reproducible and efficient population-based assessment in a Northeastern
Italian area around the city of Udine. METHODS: A retrospective population-based
analysis was conducted linking at the individual patient level, through a unique
encrypted identifier, four electronic administrative health databases, with full
coverage of the residing population: the hospital discharge database, the
ambulatory care database, the pharmaceutical prescriptions database, and the
database of exemptions from medical charges. Incident and prevalent cases of
psoriasis were identified through pre-defined algorithms. RESULTS: The estimated
prevalence of psoriasis in the study area was 1.84%, while incidence rate was
0.96/1000 person-years; 13.6% of prevalent cases had arthritis. Prevalence turned
out to increase with age and was higher in males. Arthritis was more common among
females. Biological medications were prescribed to 2% of patients in 2015.
CONCLUSIONS: Our estimates of incidence and prevalence of psoriasis and
description of patients characteristics in the North-East of Italy add knowledge
to the existing body of scientific data on the epidemiology of this disease at
the international level and provide useful information for health planners at the
local level.
PMID- 29963804
TI - Dermoscopic and laser confocal features of an exogenous ochronosis case.
PMID- 29963805
TI - Lipomatosis of the caregiver: a new form of cutaneous lipomatosis.
PMID- 29963806
TI - Treatment of facial actinic keratoses with a cream containing octatrienoic acid:
a multicenter clinical experience.
AB - BACKGROUND: Actinic keratosis (AKs) are premalignant skin lesions characterized
by high rate of transformation in squamous cell carcinoma if not treated.
Preclinical published data on parrodiene-derivative 2,4,6-octatrienoic acid,
encourages us to study and to evaluate the effect of a topical product containing
it in patients affected by mild to moderate actinic keratosis. METHODS: Seventy
subjects with at least 1-3 clinically diagnosed actinic keratosis lesions, non
hyperkeratotic, non-hypertrophic, localized on the face (I-II degree actinic
keratosis) were enrolled in the study. The product was applied twice/day for 60
consecutive days. RESULTS: After 60 days of treatment, a significant improvement
in lesions occurred as shown by the decrease in the AKESA Score (P<0.05).
Moreover, octatrienoic acid containing cream induced a 90% response rate (63/70
patients P<0.5; 95% confidence interval) with 20% complete remission (14/70
patients, P<0.05). Compared to baseline, a significant number of patients
reported improvement of each AKESA sub-score after 60 days of treatment: skin
thickness improved in 46 patients (P<0.0001), erythema in 21 patients (P<0.0001)
and atrophy in 57 patients (P<0.0348). The average pigmentation score
significantly decreased from 1.50 to 0.79 (P<0.05). CONCLUSIONS: The results of
the study, confirmed also by self-assessment, allow us not only to state that the
use of topical octatrienoic acid was effective and well tolerated for topical
treatment of AKs leading to overall clinical improvement in approximately 90% of
subjects treated for 60 days.
PMID- 29963807
TI - Skin lesions in preterm and term newborns from southern Italy and their
relationship to neonatal, parental and pregnancy-related variables.
AB - BACKGROUND: Cutaneous lesions are common in the neonatal period and usually
physiological, transient and self-limited; infrequently, they are pathological
and require treatment and collaboration between dermatologists and
neonatologists. Particular conditions, like prematurity, can influence onset,
type and evolution of cutaneous manifestations. Of the several articles in
literature about skin findings in newborns, only few were performed in Southern
European countries. We aimed to investigate dermatological findings in a sample
of neonates within the first 7 days of life and to evaluate the association
between skin lesions and neonatal, parental or pregnancy-related variables.
METHODS: 259 newborns, hospitalized in the Department of Pediatrics and Neonatal
Intensive Care Unit, Hospital "Barone Romeo", Patti (Messina), Italy, during a
six months period, were examined. All skin findings were recorded and information
on neonatal, parental and pregnancy related variables was collected and analyzed
to detect statistically significant associations. RESULTS: Skin lesions were
present in 181 newborns (69.88%). Their frequency was significantly higher in
those born to primigravida mothers (p=0.024). Erythema toxic neonatorum
prevalence was significantly higher (p=0.006) in term newborns. CONCLUSIONS: Skin
findings are frequent in newborns and often cause concern in parents and
physicians without specific experience. Thus, it is important to know and
identify them promptly to avoid unnecessary diagnostic and therapeutic
procedures.
PMID- 29963808
TI - Merkel cell carcinoma: a single-institution retrospective case series analyzing
CD271 expression with a focus on its prognostic role.
PMID- 29963809
TI - Pseudoxanthoma elasticum in Italy: epidemiological and clinical aspects.
PMID- 29963810
TI - Granulomatous tattoo reaction in a nivolumab-treated patient.
PMID- 29963811
TI - Computerized tomographic pattern of stroke seen in University of Portharcourt
Teaching Hospital.
AB - Background: Data on Computed tomographic (CT) pattern of stroke abound in
literature but they are predominantly from studies done in the Western world.
Though most of the reports agree that ischaemic rather than haemorrhagic stroke
is prevalent in most climes,no strictly radiology based study can be quoted in
the Port Harcourt area. Thus there is the need for accurate data on stroke
pattern in Nigerians of the South-South region. Aims: This study was done to
establish the CT pattern of stroke seen in University of Port Harcourt Teaching
Hospital (UPTH) and to determine the relationship between the different stroke
patterns and age, sex, including time of presentation. Methodology: A prospective
study of 203 subjects with clinical diagnosis of stroke who had CT of the brain
performed during a 12month period (November 2012 to November 2013).A 2-slice
helical CT was used to obtain images in the axial plane. Images were classified
as normal or abnormal scans. Abnormal scans were analyzed as ischaemic infarcts,
intracerebral haemorrhage, subarachnoid haemorrhage (SAH), subdural haematoma,
abscess, neoplasm, meningitis, and cerebral atrophy. The clinical diagnosis, age,
sex and time of presentation of the patients were recorded. Statistical analysis
was done with the Statistical Package for the Social Sciences (SPSS) software
version 20.0.Means were compared using Student's t test. Pearson's correlation
coefficient was used to correlate CT findings with clinical diagnosis ,age, and
sex.P values < 0.05 were considered significant. Results: The age distribution of
the study population ranged from 6-90 years with a mean of 58.3+14.9years. The
over 70 age group was most frequent with 24.1% of the subjects. Males were
predominant at 51.7% of the sample size. Findings of ischaemic cerebrovascular
disease (CVD) were more common than haemorrhagic CVD at 63.2%. Conclusion: This
study revealed a higher incidence of ischaemic stroke compared to haemorrhagic
stroke.
PMID- 29963812
TI - Percutaneous tricuspid annuloplasty.
AB - Severe tricuspid regurgitation (TR) is a common problem, affecting approximately
1.6 million Americans, with the majority (85%) of TR being functional in nature.
When left untreated, TR is associated with progressive right-sided heart failure,
with a poor prognosis entailing high morbidity and mortality. Surgical repair is
still the gold standard for TR, but only a small proportion of patients undergo
surgical repair leaving a high clinical demand for alternatives to conventional
surgery. Percutaneous repair and replacement of cardiac valves have exponentially
advanced in the past decade, including transcatheter tricuspid valve repair.
There are still anatomical challenges that need to be addressed when performing a
percutaneous transcatheter annuloplasty compared to a surgical annuloplasty, such
as approach, access, landing zone, proximal structures and visibility. Current
percutaneous annuloplasty systems either obtain a direct (Cardioband) or indirect
(TriCinch and Trialign) annuloplasty. Both direct and indirect percutaneous
annuloplasties are modeled after surgical experiences. This review will
investigate novel direct and indirect transcatheter annuloplasty devices for
repair of severe tricuspid regurgitation.
PMID- 29963813
TI - The future of percutaneous tricuspid valve interventions.
AB - Tricuspid valve regurgitation has a high prevalence and, when severe, is
associated with poor outcomes. Nevertheless, surgical repair or replacement
(isolated or as a part of a combined procedure) is rarely performed due to high
surgical risk. Therefore, there is a significant unmet clinical need for
percutaneous transcatheter-based treatments. Significant development in
percutaneous therapies for both aortic and mitral valve disease has been
accomplished over the last two decades, while transcatheter therapies for the
tricuspid valve are still at an early stage. We are today at a cross-road of new
transcatheter devices that are becoming available for the treatment of tricuspid
regurgitation; the current review evaluates the challenges that current and
future technologies have to face in order to become a safer, less invasive and
equally effective alternative to surgery.
PMID- 29963814
TI - [Transcriptome Analysis of Rabbit Spleen with Hog Cholera Lapinized Virus
Infection Based on High-throughput Sequencing Technology].
AB - In the current study, rabbit spleen was analysed at 12 h,24h,30 h,36h,and 48hpost
infection with hog cholera lapinized virus(C strain)using high-throughput
sequencing. The rabbit genome was used as a reference to identify differentially
expressed genes(DEGs)at different time points post-infection. The top 10 DEGs
were filtered based on significance, and we searched for their biological
functions through the Uniprot and NCBI databases. The former three time points
have 10co-expressing genes, many of which have a relationship to immunity and
inflammation. The latter two time points for the top 10 DEGs are identical, and
B2 M,RLA-DR-ALPHA,CD74,and IGJ are involved in the antiviral immune response. GO
functional annotation revealed that in biological processes at each time
point,except for 24hpost-infection,the immune response has the most terms,
followed by metabolism and regulation. According to the KEGG database, the DEGs
for 24hpost-infection were enriched for the RIG-I-like receptor signaling pathway
and the DEGs for 30hpost-infection were found to have a focal adhesion and ECM
receptor interaction pathway. Moreover, the DEGs for 36 hand 48hpost-infection
have seven identical pathways, of which were directly or indirectly related to
the antiviral response. These pathways included the proteasome, lysosome,
ribosome, chemokine signaling pathways, B cell receptor signaling pathway,
antigen processing, and presentation pathway, and the Fc gamma R-mediated
phagocytosis pathway.These results provide novel insight into the gene expression
in rabbit spleens post-infection with C strain, and provide a theoretical basis
for further understanding of the molecular mechanisms by which rabbits adapt to
infection with C strain.
PMID- 29963815
TI - Effect of education and training on patient referral by public primary health
care workers in Mushin Local Government Area to state general hospitals in Lagos,
Nigeria.
AB - Background: Poor referral linkages had been noted and documented by various
researchers on the health care delivery system in Nigeria. This study is designed
to find out the situation of referral practices and make recommendations on how
to improve the situation. Material and Method: A total sample of 170 primary
health care workers was involved in the study:85 in each of the Local Government
Areas. The study involved three stages, the pre-intervention, the intervention
phase, and a post intervention phase of the study. Results: In the post
intervention phase the differences in the responses between the two groups in the
area of practice of patient referral were statistically significant. In the
control group 18.8% of the workers used the two-way referral form in the pre
intervention phase. This rose to 27.1% in the post intervention phase. In the
experimental group, 17.5% used the two-way referral form in the pre intervention
phase, and this rose to 69.4% in the post intervention phase. Conclusion: The
conclusion was that education and training on patient referral could improve the
patient referral activities of primary health care workers.
PMID- 29963816
TI - [Gene Characteristic Analysis for The VP1 Region of Coxsackievirus A6 Associated
with HFMD in the Anyang Area of China during 2013].
AB - This study aims to investigate the etiologic spectrum features of hand, foot and
mouth disease(HFMD)and the VP1 region of coxsackievirus A6(CV-A6)in the Anyang
area of China during 2013.A total of 479 HFMD fecal specimens were identified
using real-time RT-PCR. The positive specimens of the different serotypes and the
proportion of each serotype were calculated. A total of 10 positive of CV-A6
specimens were amplified and sequenced to obtain the profile of the VP1 region.
Based on the data of the VP1 sequences from the Anyang strains and other
referenced strains deposited in the NCBI database, the similarities of the
nucleotide and amino-acid sequences for the VP1 region, as well as phylogenetic
analyses were performed by the BIOEIDT 7.2and MEGA 5.1software packages. The
results revealed that 429 positive specimens of enterovirus, including 90
positive specimens of CV-A6 were identified. The CV-A6 specimens accounted for
20.98%of the total positive specimens.CV-A6 had become the second preponderant
pathogen of the HFMD in the Anyang area during 2013.It was the first record of an
enterovirus serotype of which was neither CV-A16 nor EV-A71,had become one of the
primary pathogens associated with HFMD in the region. A great diversity of the
nucleotide and amino-acid sequences between 10 Anyang strains and a prototype
strain (Gdula) was found. Compared with the Henan strain(HN421),four Anyang
sequences with nucleotide and amino-acid sequences exhibited greater diversity
than the other six Anyang sequences. The phylogenetic analysis showed that all of
49CV-A6 strains could be clustered into four branches. Branch D could be further
clustered into two sub-branches;6 Anyang sequences belonged to sub-branch D1,and
the other four belonged to sub-branch D2.
PMID- 29963818
TI - Efficacy of peritonsillar infilltration of ketamine, tramadol, and lidocaine for
prevention of post tonsillectomy pain.
AB - Backgrounds: Tonsillectomy is one of the most common surgeries in children.
Controlling pain after tonsillectomy is still controversial. In this study, the
efficacy of peritonsillar injection of lidocaine, tramadol, ketamine, and placebo
is compared on post tonsillectomy pain. Methods: In a randomized double-blind
clinical trial, 120 patients referring for tonsillectomy to Imam Khomeini
hospital in Ahvaz, Iran were recruited into four groups: ketamine, tramadol,
lidocaine, and normal saline. One milliliter of medications was injected in each
tonsil. Surgery was performed by a surgeon with sharp dissection technique
without electrocautery. Pain was recorded 1, 4, 8, 16, and 24 hour(s) after the
operation Results: Baseline characteristics such as age, sex, weight, height, and
surgery and anesthesia time did not differ significantly among four groups. Pain
scores decreased over time in all groups. No significant difference was observed
among ketamine, tramadol, lidocaine, and placebo regarding pain quantity, surgery
time, the first time of analgesic requirement, hospital stay, and beginning
liquid diet. Conclusion: Local injection of ketamine, tramadol, and lidocaine
were not significantly different from placebo for prevention of pain in the first
24 hours after tonsillectomy.
PMID- 29963819
TI - [Functional Analyses of HIV-1 Specific Cytotoxic T Lymphocyte Clones].
AB - Human immunodeficiency virus type 1(HIV-1)-specific CD8 cytotoxic T
lymphocytes(CTL)are essential components of the protective immunity against HIV
1infection.However,due to heterogeneous responses of CTL to HIV-1,our general
understanding of CTL efficacy in the context of HIV-1infection remains limited.
To better understand the factors that determine the potency of HIV-1specific CTL
responses, this study directly investigated the relationship between different
functional attributes associated with CTL response at the single cell level by
using HIV-1specific CTL clones isolated in vitro. Twelve selected HIV-1CTL clones
with various HLA restriction and specific antigen epitopes were comprehensively
evaluated by several functional assays(e.g., killing capacity, degranulation,
production of multiple cytokines and polyfunctionality, as well as the expression
of lytic granule components and exhaustion molecules).Our principal findings were
that the killing capacity of the CTL response was most closely associated with
their degranulation capacity. Additionally, the killing and the degranulation
capacity of CTL was associated with the levels and polyfunctionality of the
cytokines secreted later. These findings implicate that multiple functional CTL
responses are coordinately regulated and determined.
PMID- 29963817
TI - Changes in tuberculosis in human immunodeficiency virus infected patients in a
Spanish tertiary hospital (1995-2013).
AB - OBJECTIVE: Although the incidence of human immunodeficiency virus (HIV)
associated tuberculosis (TB) has decreased, changes in other characteristics of
the disease are largely unknown. To describe the trends in TB in patients
infected with HIV from 1995 to 2013. METHODS: We review all cases of TB in a
tertiary hospital in Madrid, Spain. RESULTS: Among 1,284 patients diagnosed of
TB, 298 (23%) were coinfected with HIV. The prevalence of HIV infection during
the period of study has decreased from 40% to 14% (p for the trend < 0.001).
Clinical presentation has also changed. Although pulmonary and extrapulmonary TB
has remained unchanged, miliary presentation has significantly decreased (from
36% to 22%, p = 0.005). The 4-drug regimen was the preferable scheme, with higher
implementation at the end of the study period (82% from 1995-1999 to 95% in 2010
2013, p = 0.43). Factors such as treatment failure (OR: 11.7; CI 95%: 3.12-44.1)
and miliary form (OR: 2.8; CI 95%; 1.09-7.3) were independently associated with
TB related mortality, while the longer duration of treatment was as a protective
factor (OR 0.7; CI 95%: 0.6-0.8). CONCLUSIONS: HIV has decreased very
significantly as a risk factor for the development of TB. Despite improvement in
the treatment of both TB and HIV, and in overall mortality, deaths attributable
to the disease in this population remain high mostly in miliary and relapsing
forms.
PMID- 29963820
TI - Overweight and obesity status of school adolescents in Portharcourt, southern
Nigeria.
AB - Background: Adolescent overweight and obesity has been linked to obesity in adult
life, with its associated risks of chronic diseases including cardiovascular
diseases. Thus, prevention aimed at early screening and surveillance should be
the key. The aim of this study is to determine the prevalence of overweight and
obesity among schooling adolescents in Port Harcourt. Mateials and Methods: A
cross sectional study was carried out on 2,282 secondary school students aged 10
19 years, using a structured questionnaire to obtain data. Weights and height
were measured using standard methods. The Body Mass Index (BMI) was calculated
from their weights and heights in kg/m.2 The nutritional status of the students
was determined using the BMI percentile charts for age and gender as recommended
by the World Health Organisation in 2007. Results: The prevalence of overweight
and obesity were 13.2% and 4.6%.The female subjects had a higher prevalence of
overweight and obesity (14.6% and 5.2%) than the males (11.4% and 3.8%) and this
difference was statistically significant (P = 0.041). Conclusion: The prevalence
of overweight and obese adolescents in Port Harcourt is high. We recommend that
health education with emphasis on lifestyle changes and behavioral modification
that will promote healthy eating and regular physical activities be inculcated
into the curriculum of secondary schools in Nigeria.
PMID- 29963821
TI - [Expression,Purification,Structure Determination and Immunogenicity Assay of
Hepatitis E Virus Capsid Protein p495 Derived from Baculovirus-based Insect
Cell].
AB - Our objective was to establish a robust method for the expression and
purification of hepatitis E virus(HEV)p495protein using a baculovirus-based
insect cell expression system; to determine the properties and cryo-EM structure
of the resulting virus-like particles(VLPs);and to compare their immunogenicity
with p239 particles in the commercial hepatitis E vaccine (Hecolin). The sequence
spanning HEV ORF2 amino acids 112-606 in the genotype I HEV isolate was cloned
into baculovirus to express recombinant p495 protein. ELISA, analytical
ultracentrifugation, size-exclusion chromatography and negative-staining
transmission electron microscopy(TEM)were carried out to characterize the
physicochemical properties of p495.Recombinant p495 VLPs were obtained
successfully from the insect cell expression system with purity of>95%and yield
of 15mg/L.The recombinant HEV p495 protein was homogeneous in solutions. The
3Dstructure of p495 VLPs was determined by cryo-EM;it was icosahedral with
T=1arrangement,and showed good congruency with the crystal structure in the
literature(PDB ID:2ZZQ).In mouse vaccination experiments,p495 conferred
comparable immunogenicity with that of p239 antigen in Hecolin. Thus, a robust
and scalable approach to obtain homogeneous, immunogenic HEV p495 VLPs has been
established. This study may assist investigations of HEV receptors, epitope
mapping, vaccine improvement and so on.
PMID- 29963822
TI - Blood pressure indices and disease severity in patients with sickle cell anaemia.
AB - Background: Individuals with sickle cell anaemia (SCA) have lower systemic blood
pressures compared to individuals with haemoglobin Hb AA phenotype. Objective:
Seventy-nine (79) individuals with SCA (subjects) in steady state and 50 age
matched individuals with Hb AA (controls) were prospectively studied. Height,
blood pressure (BP), weight, creatinine clearance (by 24-hour urine collection),
full blood count (FBC) and reticulocyte count were obtained from all subjects and
controls. Body mass index (BMI), corrected reticulocyte count, mean arterial
pressure (MAP) and pulse pressure (PP) were calculated using standard
protocols.The frequency of vaso-occlusive crises in the last one year and number
of blood transfusions in the last two years were obtained from subjects. Data was
analyzed using descriptive and inferential statistics and p <=0.05 was used to
define the level of statistical significance. Methodology: Seventy-nine (79)
individuals with SCA (subjects) in steady state and 50 age-matched individuals
with Hb AA (controls) were prospectively studied. Height, blood pressure (BP),
weight, creatinine clearance (by 24-hour urine collection), full blood count
(FBC) and reticulocyte count were obtained from all subjects and controls. Body
mass index (BMI), corrected reticulocyte count, mean arterial pressure (MAP) and
pulse pressure (PP) were calculated using standard protocols.The frequency of
vaso-occlusive crises in the last one year and number of blood transfusions in
the last two years were obtained from subjects. Data was analyzed using
descriptive and inferential statistics and p <=0.05 was used to define the level
of statistical significance. Results: The systolic (105.52+/-11.75mmHg and
113.20+/-7.94mmHg respectively; P = 0.01), diastolic (62.59+/-9.33mmHg and
75.40+/-5.70mmHg respectively; P=0.03) and mean arterial pressures (76.90+/
8.81mmHg and 88.00+/-5.51mmHg respectively; P =0.04) were significantly lower in
subjects when compared with controls. ; pulse pressure (PP) was however
significantly higher in subjects than controls (42.92+/-10.91mmHg and 37.80+/
7.43mmHg respectively (P = 0.03). In female subjects, the white cell count was
negatively correlated with systolic BP (r = -0.39;P = 0.01) and PP (r = -0.33; P
= 0.03). Conclusion: Lower systolic and pulse pressures may predict worsening
disease severity in individuals with sickle cell anaemia.
PMID- 29963823
TI - [Development of Novel Multiplex Real-time RT-PCR Assays for Detection of MERS-CoV
Infection].
AB - We aimed to develop a novel laboratory assay for the detection of Middle East
respiratory syndrome coronavirus (MERS-CoV) infection .Several novel multiplex
real-time RT-PCR assays were developed using the upE,ORF1 band N2genes of MERS
CoV as targets; the novel assays were compared with previous monoplex real-time
RT-PCR assays. For validation, we tested a MERS-CoV strain (hCoVEMC), clinical
specimens from patients with fever in Shanghai, and specimens from the first
imported MERS case in China. The detection limit of the novel multiplex real-time
RT-PCR assays was 10 PFU of MERS-CoV per ml, the same as that in monoplex real
time RT-PCR assays based on upE or N2. The detection was specific for MERS-CoV.
In validation using clinical samples, pharyngeal swabs from Shanghai patients
were detected as negative, while swabs from the first imported MERS case in China
were detected as positive. Using whole blood samples from a MERS case, better
detection results were obtained with N2 as the target than upE. We conclude that
all the novel assays established in this study could be used for the detection of
MERS-CoV; they show potential for improvement compared with monoplex real-time RT
PCR assay based on upE.
PMID- 29963824
TI - Pattern of prostate cancer among a Nigerian population: A study in a single
tertiary care centre.
AB - Background: Prostate cancer has become a global health challenge because of its
rising morbidity and mortality in males. It is the second cause of cancer death
following lung cancer in men. It is rare under the age of 40 and its incidence
has been shown to increase exponentially with age. Previously, Prostate cancer
was thought to be a disease rare in blacks owing to the fact that not so much was
known of the disease. Aims and Objectives: The objective of the study was to
review the prevalence, pattern of presentation and clinic-pathologic findings of
prostate cancer in the Department of Radiotherapy, Lagos University Teaching
Hospital (LUTH), between January 2001 to December 2010 in comparison to previous
and recent studies globally. Methodology: Data collection for all patients
histologically diagnosed with Prostate cancer at the Department of Radiotherapy,
LUTH, from 1st of January 2001 to 31st of December 2010 was done. Results: A
total of 144 cases with histologically confirmed Prostate cancer seen during the
ten year study were analysed. The highest frequency was seen in the year 2010
with 34 cases. The age range was 41 to 81years with a mean of 66.19 +/
7.30years.Adenocarcinoma was the commonest histological type with 98.6%.9(6.3%)
patients had a positive family history of prostate cancer out of which 3(33.3%)
had their brother affected the malignancy. 51(35.4%) patients presented with
stage IV disease.18(12.5%) patients had a Gleason's score of 6,10(6.9%) patients
had a Gleason's score of 7 and 2(1.4%) patients had a Gleason's score of 10. The
most common presenting complaints were bone pains seen in 51(35.4%) patients,
frequent night urine and difficulty with micturition seen in 50(34.7%) and
42(29.2%) patients respectively. Conclusion: This study showed that prostate
cancer is not as rare as it used to be. Reasons attributed to its rarity then
were lack of awareness, poor screening facilities and poor diagnosing technique.
PMID- 29963825
TI - [Research Progress in Viral Protein Vpx induction of Proteasomal Degradation of
the Antiviral Factor SAMHD1].
AB - HIV the pathogen responsible for the transmission of AIDS, which is associated
with a high mortality rate. Vpx is expressed in HIV-2/SIV and promotes retroviral
infection in specific cells. This promotion is achieved by Vpx-induced formation
of the CRL4E3 complex, which removes the endogenous SAMHD1 via proteasomal
degradation. Multiple domains of SAMHD1(e.g., N-terminus, nuclear localization
signal, linker, HD domain, and C-terminus)are essential for Vpx-induced
degradation.HIV-1that does not express Vpx is also evolved with mechanisms to
bypass or suppress the antiviral function of SAMHD1,such as the tolerance against
a low level of dNTPs and induction of SAMHD1 degradation through cyclin L2.Based
on previous reports published chronologically, as well as the latest findings in
the field, this review focuses on the mechanism of Vpx-mediated degradation of
SAMHD1,and its promotion of HIV-1infection.
PMID- 29963826
TI - Pathogenesis of benign unilateral adrenocortical tumours: focus on cAMP/PKA
pathway.
AB - Somatic mutations affecting genes in the cAMP/PKA (Protein Kinase A) signaling
pathway have been described as causative for the pathogenesis of benign
unilateral adrenocortical adenomas associated with cortisol over secretion. These
include predominantly somatic mutations in the PRKACA gene which encodes the
catalytic subunit alpha of PKA. In addition, mutations in the GNAS gene, coding
for the stimulatory G protein alpha, have been observed in approximately 10 % of
cortisol producing adenomas (CPAs). The mutations render PKA signaling
constitutively active and are therefore involved in cortisol over secretion of
these tumours. Despite the prominent role of the cAMP/PKA pathway in the
pathogenesis of unilateral CPAs, also mutations in the CTNNB1 gene, encoding beta
catenin, were identified in CPAs. However, mutations in beta-catenin are not
limited to CPAs and are not associated with cortisol secretion since they were
predominantly found in endocrine-inactive adenomas (EIAs) and might hence
contribute to tumorigenesis in adrenocortical tissues. In this review, recent
findings in the pathogenesis of benign adrenocortical tumours with a particular
focus on the cAMP/PKA signaling pathway are summarised.
PMID- 29963827
TI - The role of Insulin-like Growth Factor (IGF) system in the adrenocortical tumors.
AB - INTRODUCTION: The different presentation of adrenocortical tumors in benign
adenoma (ACA) or adrenocortical carcinoma (ACC) is related to the variability at
the molecular level. The insulin-like growth factor (IGF) system is one of the
most frequently altered pathways in ACC. In this review we will critically
analyze the evidence regarding the pathogenic role of the IGF system in adrenal
tumorigenesis, focusing on ACC. We will also examine the pre-clinical and
clinical studies which investigated the targeting of the IGF system as a
therapeutic approach in ACC. EVIDENCE ACQUISITION: The IGF system plays a crucial
role in the embryogenesis of adrenal glands. No significant alterations of the
IGF system were observed in ACA. In ACC, the IGF2 overexpression is one of the
most frequent molecular change presented in more than 85% of cases. However, IGF2
seems to be only a tumor progression factor which requires additional hits to
trigger adrenal tumorigenesis. Also, the IGF1R appears to be higher expressed in
ACC. Many IGF1R target-drugs have been developed to inhibit the activation of the
IGF system. Preclinical studies using antibody or tyrosine kinase which target
the IGF1R, or the dual-targeting of IGF1R and insulin receptor (IR) reduced ACC
cells proliferation both in vitro and in vivo in mouse xenograft model. However,
these promising results were not confirmed in clinical trials. CONCLUSIONS:
Nowadays, predictive markers for the response of target-IGF therapy are missing
and further studies which investigate new molecular markers and evaluate the
entire IGF receptors, including the IR, are urgently needed.
PMID- 29963828
TI - Autonomous hypercortisolism: definition and clinical implications.
AB - In current practice, an adrenal adenoma usually comes as an unexpected byproduct
of an imaging study performed for unrelated reasons, without any prior suspect of
adrenal disease. Therefore, these tumors currently represent a public health
challenge because they are increasingly recognized due to the widespread use of
high-resolution cross-sectional imaging for diagnostic purposes. In radiology
series, the prevalence of adrenal adenomas increases steeply with age, from
around 3% below the age of 50 years up to 10% in the ageing population. These
tumors may have clinical relevance because they are able to secrete cortisol
autonomously, independently from the pituitary control, in up to 20% - 30% of
patients. In most of the cases the resulting cortisol excess is insufficient to
produce a typical Cushing phenotype but may have clinical consequences, such as
hypertension, diabetes, obesity, dyslipidemia and osteoporosis. Despite some
controversy on the most effective diagnostic algorithm to define this subtle
hypercortisolism, there is mounting evidence that a simple approach by using the
1-mg overnight dexamethasone suppression test (DST) may stratify patients for
their cardiovascular risk. Cross- sectional, retrospective studies showed that
patients with increasingly higher cortisol following DST have an adverse
cardiovascular risk profile and are at increased risk of death. Therefore, also a
subtle autonomous cortisol excess is associated with increased morbidity and
mortality, mainly of cardiovascular origin.
PMID- 29963830
TI - Is heme oxygenase-1 turning out to be a key positive regulator for oxidative
stress?
PMID- 29963829
TI - Assessment of knowledge and sexual behaviour among undergraduates in a Nigerian
tertiary institution.
AB - Background and Introduction: The achievement of the Millennium Development Goals
(MDGs), particularly goals 5 and 6, is strongly underpinned by the progress that
can be made on sexual and reproductive health education of young adults. The
large population of young single adults in tertiary institutions in Nigeria and
the present dearth of human resources for health necessitates that interventions
for this group of individuals are tailored to meet identified gaps in awareness
and sexual behaviour. This study sets out to assess the sexual behaviour and
practice among single-undergraduates in a tertiary institution in Nigeria.
Method: A descriptive cross sectional study was carried out among 410 consenting
students selected through a multistage sampling method. Data was collected using
a structured self- administered questionnaire and analysed using Statistical
Package for Scientific Solutions (SPSS) version 16.0. Results: Mean age of
respondents was 20 + 4.4 years, 228 (55.6%) were females and 182 (44.4%) males.
The respondents' awareness of contraceptive devices was 81.7% (335) for condoms
and less than 20% knew about other forms of contraception such as intrauterine
device, tubal ligation and vasectomy. Over 65.7% (270) opined abstinence and use
of condom to be the ideal methods for prevention of HIV/AIDS/ STI transmission.
The overall mean age at first sexual contact was 14.0+1.4((14.2+1.6) in males and
(13.8 +1.2) in females). A Very high proportion of sexually active respondents
(93.6%) volunteered they do not routinely use condom in their sexual encounter.
Undesired pregnancies occurred in about 11% of females. Recommendations: There is
an urgent need for the establishment of specially designated youth friendly
centres in the tertiary institutions in the country, manned with staff
appropriately trained in the delivery of reproductive health information and
services.
PMID- 29963832
TI - Alcoholic liver disease and vitamin D deficiency.
PMID- 29963831
TI - Vitamin D supplementation in patients with alcoholic liver cirrhosis: a
prospective study.
AB - BACKGROUND: The liver is involved in the metabolism of vitamin D. The prevalence
of osteopenia in alcoholic liver disease (ALD) patients is 34-48%, and the
prevalence of osteoporosis is 11-36%. Advanced liver disease is considered a risk
factor for the development of osteoporosis. The aim of this study was to
establish the relationship between vitamin D level and Child-Pugh score in
patients with alcoholic liver cirrhosis (ALC), and to evaluate the effects of
oral vitamin D supplementation. METHODS: Seventy male ALC patients in the absence
of active alcohol intake were enrolled and their clinical and laboratory data
were recorded. A supplementation of cholecalciferol 1000 IU/day was administered.
The vitamin D status was analyzed during the study, in patients stratified by
Child-Pugh score. RESULTS: The study was completed by fifty patients. At the
enrollment, the mean level of vitamin D was 60.73+/-28.02, 50.53+/-39.52 and
26.71+/-12.81 nmol/L, respectively for Child-Pugh score class A, B and C. During
vitamin D supplementation it was found in all the patients a significant increase
of its levels during the first six months (P<0.05). However, in class C the
improvement was consistent also after year (P<0.05). At the end of the study, two
of seven patients initially in class C changed in class A, four from class C to
B, and one remained in class C (P=0.012). Out of seventeen patients initially in
class B, eleven changed to class A, and six remained in class B. CONCLUSIONS: In
patients with ALC, higher level of vitamin D level is related with lower Child
Pugh score. The supplementation of 1000 IU/day of vitamin D in these patients was
optimal for a period of at least six months. A decrease in the Child-Pugh score
was also found, with a redistribution of the patients in different classes.
PMID- 29963833
TI - Addiction disorders: a need for change. Proposal for a new management. Position
paper of SIA, Italian Society on Alcohol.
AB - Various epidemiological and biological evaluations and the recent publication of
the DSM-V (diagnostic and statistical manual of mental disorders) has imposed on
the scientific community a period of reflection on the diagnosis and treatment of
what in the DSM-IV was defined as "addiction". To date, the term "addiction" has
been replaced by the DSM-5, because there is no global scientific consensus that
has unequivocally characterized its clinical characteristics. This, we will talk
about substance/alcohol use disorders (SUDs/AUDs) and disorders related to
behavioral alterations (DBA) that can generate organic diseases, mental
disorders, and social problems. In the first psychotic episode 40-70% of subjects
meet the criteria of a SUDs/AUDs, excluding tobacco dependence. Substances can
not only be the cause of a psychotic onset, but they can also disrupt a psychotic
picture or interfere with drug therapy. The pharmacodynamic profiles of many
substances are able to provoke the phenomenology of the main psychotic symptoms
in a way that can be superimposed onto those presented by psychotic subjects
without a history of SUDs/AUDs. The Department of Addictions (DAs) must not be
absorbed by or incorporated into the Departments of Mental Health (DMH), with
which, however, precise operational cooperation protocols will have to be defined
and maintained, but it will have to maintain its own autonomy and independent
connotation. Addiction Medicine is a discipline that brings together elements of
public health, prevention, internal medicine, clinical pharmacology, neurology,
and even psychiatry. The inclusion of the DAs in those of DMH refers purely to a
problem of pathology that has to do with lifestyle, choices, and behaviors.
These, over time, show their dysfunctionality and only then do related problems
emerge. Moreover, epidemiological, social, and clinical motivations impose the
creation of alcohological teams dedicated to alcohol-related activities. The
collaboration with self-help-groups (SHGs) is mandatory. The action of SHGs is
accredited in numerous international recommendations both on the basis of
consensus and evidence in the literature.
PMID- 29963834
TI - Sclerosing mesenteritis: A case of acute abdomen and intestinal obstruction.
AB - Sclerosing mesenteritis (SM) is a rare idiopathic disorder characterized by
chronic non-specific inflammation involving the adipose tissue of the bowel
mesentery. It may be asymptomatic but it commonly presents with abdominal pain.
Some individuals may have a palpable abdominal mass and affected individuals may
develop small bowel obstruction or acute abdomen.We report a case of 27-year old
man who presented to the Surgery Department at Chukwuemeka Odimegwu Ojukwu
University Teaching Hospital (COOUTH), Amaku Awka, Anambra State with acute
abdomen and intestinal obstruction. He subsequently, had a surgical resection,
which was histologically confirmed as a sclerosing mesenteritis. Sclerosing
mesenteritis is a rare disorder and this is the first case being reported in the
literature from South-East, Nigeria.It is therefore, important to alert
physicians, more especially the surgeons on the need to have a high index of
suspicion in every case of intestinal obstruction.
PMID- 29963835
TI - [Research Progress in Enveloped Glycoproteins and the Membrane-fusion Mechanism
of Nipah Virus].
AB - Nipah virus (NiV) is the pathogen of an emerging zoonotic disease that is highly
lethal and infectious. NiV seriously impacts human lives and the property in the
epidemic areas and poses a great threat to the global public health security.
This paper provides a brief introduction to the morphological structure, and
physiological function of the attachment protein G and the fusion protein F,
which are both crucial glycoproteins located on the surface of the virus
envelope. Moreover, recent advances in domestic and international research are
reviewed. We will consider tissue tropism to elaborate the interactive mechanism
between the attachment protein and its protein receptors ephrin-B2/B3,as well as
the interactions between the two glycoproteins in detail. Avenues of future
research are also discussed.
PMID- 29963836
TI - Bladder calculus resulting from an intravesical translocation of intrauterine
contraceptive device in a postmenopausal woman.
AB - Although perforation of the uterus by an intrauterine contraceptive device (IUCD)
is commonly encountered, intravesical translocation and secondary calculus
formation is a very rare complication. We report a case of a 60-year old
multiparous woman in whom an intrauterine contraceptive Copper-T device inserted
12 years earlier translocated from the uterus to the bladder and resulted in
formation of a calculus. Diagnosis was established with pelvic ultrasonography
and plain abdominal radiograph. The cystoscopic removal was not successful due to
the large size of the calculus. The patient later underwent cystolithotomy.
Sonographic follow-up immediately after the insertion and at six month intervals
will go a long way in early detection of any possible complications.
PMID- 29963837
TI - [Advances in the Animal Models of MERS-CoV].
AB - The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in
2012 from patients that died from severe pneumonia. It was another coronavirus
which resulted in severe infection of humans, apart from the severe acute
respiratory syndrome coronavirus. The development of an appropriate animal model
is necessary to study the pathogenesis and to evaluate the intervening measures
against MERS-CoV infection. To date, several small animals(e.g., mice, Syrian
hamsters, and ferrets) have been used to study MERS-CoV infection. In addition,
rhesus macaques, common marmosets, and dromedary camels were also utilized as the
models for MERS-CoV study. The purpose of this paper is to summarize the
advantages and disadvantages of the animal models mentioned above, to provide a
thorough understanding of the MERS-CoV study.
PMID- 29963838
TI - Hypereosinophilic syndrome with severe hypokalaemia in a Nigerian woman: A case
report.
AB - Introduction: Hypereosinophilic syndrome (HES) is a rare disorder. It is defined
as eosinophilia of greater than1.5x109 /L persisting for at least 6 months or
death before 6 months without an identifiable cause and with eosinophil-mediated
organ dysfunction. We present a rare case of hypereosinophilic syndrome with
severe hypokalaemia in a Nigerian female patient. Case Presentation: A 43year old
food vendor referred to the Haematology Department, University College Hospital,
Ibadan on account of a 6-week history of cough productive of mucoid, brownish,
foul smelling sputum with associated breathlessness, high grade intermittent
fever, and intense pruritus. She had accompanying non-projectile,non-bloody
vomiting of recently ingested meals. There was absolute eosinophilia of 83x109/L
and bone marrow cytology revealed marked eosinophilia with blasts of less than
5%. She also had asymptomatic severe hypokalaemia (1.9mmol/l) likely due to
vomiting and reduced dietary intake. The aetiology of the hypereosinophilia could
not be ascertained.She was admitted and commenced on intranasal oxygen, Tabs
Loratidine, intravenous hydration.The severe hypokalaemia was corrected with IV
KCL over 48hours followed with the administration of slow K tablets 600mg tds.
She also had tabs Hydroxyurea for cytoreduction and Allopurinol to prevent
hyperuricaemia. She improved with the above line of management. Conclusion: This
appears to be the first reported case of HES with asymptomatic severe
hypokalaemia in the literature. Being a rare disorder it could easily have been
missed without a review of the peripheral blood film and marrow aspirate. This
finding suggests a possible relationship between hypereosinophilia and
hypokalemia which needs to be explored.
PMID- 29963839
TI - [Exploring the Natural Reservoirs of the Novel Homologs of Hepatitis C Virus].
AB - Hepatitis C virus(HCV)infection is a global public health problem, primarily
triggering acute and chronic liver hepatitis. Owing to the narrow host range, a
suitable animal model is still lacking, hindering study of viral pathogenesis,
immune control,and prophylactic vaccine development. There has no relevant
evidence that homologs of HCV originating from the animal may have the potential
to cross the species barrier to cause human disease until recently. Several
agents discovered that new viruses related to HCV, including HCV and GBV-like
viruses(belonging to the Hepacivirus and Pegivirus genera, respectively), in
small wild mammals (e.g., rodents and bats)and domesticated animals(e.g., dogs,
horses, and cattle). Genetic and biological characterization of these novel HCV
related viruses may provide novel insight into the origins, pathogenesis, and
immune response to HCV infection in humans. In this review, we introduce the gene
characteristics of HCV, concerned viruses, and many newly discovered viruses
closely related to HCV-like viruses. The exploration of their natural reservoirs
will be performed, and we then discuss possible theories regarding the origin of
this important viral human pathogen.
PMID- 29963840
TI - Signet ring lymphoma: The import of immunohistochemistry in resolving diagnostic
dilemmas.
AB - Signet ring cell lymphomas are a rare subtype of non Hodgkin lymphoma
characterised by malignant lymphoid cells with cytoplasmic inclusions that
displace the nucleus and imparts a "signet ring" appearance. This poses a
diagnostic challenge as it can be mistaken for an adenocarcinoma or any other
epithelial malignancy. A 54yr old male presented with a 6month history of
generalised lymphadenopathy. Examination of excision biopsy of the lymph nodes
show effacement of architecture by sheets neoplastic cells with abundant
cytoplasm distended by eosinophilic amorphous substances. Immunohistochemistry
with a panel of three monoclonal antibodies [LCA, CD20, and CD3] confirmed these
cells to be of lymphoid origin.
PMID- 29963841
TI - [Research Progress in Laboratory Diagnostic Methods for HEV Infection].
AB - Hepatitis E, an acute self-limited disease is caused by hepatitis E virus(HEV)and
is a public-health concern for people worldwide. HEV is transmitted primarily via
the fecal-oral route while direct evidence for blood-borne transmission has been
reported. So the risk of blood transfusion safety caused by HEV has been widely
paid attention. Here, we aim to provide some references to HEV screening for
blood donors through analyzing the existing diagnostic methods for HEV, which are
of great significance for the prevention and control of HEV infection. Currently,
the primary detection indexes for HEV primarily include HEV RNA,HEV antigen, anti
HEV IgM, and anti-HEV IgG. HEV RNA testing is considered to be the "gold
standard" for the detection of HEV infection. This test takes advantage of
patients with chronic Hepatitis E, immunosuppressed people, and patients with
nonhepatic manifestations of hepatitis E.HEV antigen testing is regarded as a
current infection index for HEV, which could be used to detect HEV in blood
donors and diagnose acute HEV infection. Anti-HEV IgM is a mark of HEV recent
infection, but not a single index to diagnose a current infection with HEV. Anti
HEV IgG indicates that HEV was the previous infection, and it is not suitable to
diagnose acute HEV infection. At present, blood donors screening for HEV were
mainly based on nucleic acid detection, and an antigen test possibly could cover
its' shortage. To confirm the value of the antigen and antibody tests for blood
donor screening, further studies are required in the future.
PMID- 29963842
TI - Musculoskeletal Therapies: Foreword.
PMID- 29963843
TI - Musculoskeletal Therapies: Osteopathic Manipulative Treatment.
AB - Osteopathic manipulative treatment (OMT) is being used increasingly in the United
States. OMT techniques can be categorized as direct, using an activating force to
move tissue through range-of-motion barriers; indirect, disengaging dysfunctional
body parts away from restrictive barriers; and combined techniques. Evidence
supports the effectiveness of this therapy in management of musculoskeletal
conditions, particularly for low back pain, but is limited for many other
conditions. Physician opinion, patient reporting, and student attitudes about OMT
primarily are positive, but rates of OMT use vary across different US regions.
Adverse effects are rare but include cauda equina syndrome, lumbar disk
herniation, fracture, and hematoma or hemorrhagic cyst. Contraindications to OMT
primarily involve conditions that increase bleeding risk or compromise bone,
tendon, ligament, or joint integrity. National organizations have issued
recommendations and guidelines recommending OMT as a first-line noninvasive
therapy for low back pain after self-care. OMT is covered by many health
insurance companies and training is available for allopathic physicians. Patient
referrals should be made to appropriately credentialed physicians after
consideration of supporting evidence and patient interest.
PMID- 29963844
TI - Musculoskeletal Therapies: Adjunctive Physical Therapy.
AB - Physical therapy (PT) modalities are a diverse group of treatments for
musculoskeletal pain. Iontophoresis, phonophoresis, kinesiology taping, laser
therapy, and myofascial release are some of the most commonly used and are best
considered as adjuncts to exercise. Each modality is relatively safe, but none is
supported by high-quality evidence in the management of most musculoskeletal
conditions. Individual patient response to such modalities is variable. Neither
iontophoresis nor phonophoresis has been shown to have greater benefits for neck
or back pain than supervised PT. However, use of phonophoresis has been shown to
result in a small improvement when added to therapeutic exercise. Kinesiology
taping improves symptoms for patients with plantar fascia pain, pes anserine
bursitis, and low back pain (LBP). Laser therapy has shown small benefit in
chronic LBP and shoulder disorders including adhesive capsulitis, calcific
tendinitis and rotator cuff tendinopathies. Myofascial release, has been found to
improve symptoms of neck pain. These modalities should never replace active PT,
but their use should not be discouraged as part of a comprehensive program. A
concern is cost because many health insurance companies consider these therapies
to be medically unnecessary or experimental.
PMID- 29963845
TI - Musculoskeletal Therapies: Musculoskeletal Injection Therapy.
AB - Injections often are used in the management of common musculoskeletal conditions.
Physicians should understand the disease pathophysiology and evidence supporting
available injections when determining appropriate therapy. These therapies
include corticosteroid injections (CSIs), hyaluronic acid (HA) injections,
hypertonic dextrose prolotherapy, platelet-rich plasma (PRP) injections,
mesenchymal stem cell (MSC) injections, and trigger point injections (TPIs). CSIs
are recommended conditionally by the American College of Rheumatology for
osteoarthritis (OA) management. CSIs are associated with short-term improvement
in pain and function in patients with OA, although cartilage volume loss can
occur with repetitive, frequent use. CSIs show no long-term benefit in the
management of lateral epicondyle pain. For knee OA, HA injection shows prolonged
improvement of pain and function compared with CSI. Studies of HA injection for
other joints show the injection to be no more effective than placebo. Evidence
for prolotherapy and PRP injection shows long-term improvement of pain and
function in knee OA and tendinopathies. There is low-quality evidence showing MSC
injections improve pain and function in OA and tendinopathies. It is unclear
whether TPIs are effective because of a lack of high-quality evidence.
Ultrasonography guidance has been shown to improve accuracy of delivery and
clinical outcomes in injection therapies.
PMID- 29963846
TI - Musculoskeletal Therapies: Acupuncture, Dry Needling, Cupping.
AB - Integrative medicine, including acupuncture, dry needling, and cupping, is being
used increasingly in the United States. Evidence regarding their efficacy in the
management of musculoskeletal conditions is heterogeneous and subject to several
limitations. Despite these limitations, acupuncture consistently has been shown
to be more effective than no treatment and is relatively safe. For chronic back
pain, it is recommended as a first-line noninvasive therapy. For neck pain,
acupuncture provides benefits when it is combined with other treatments. Dry
needling is similar to acupuncture and frequently is regarded as a form of
acupuncture. Evidence similar to that for acupuncture supports the use of dry
needling for patients with localized musculoskeletal pain conditions. The effects
of these procedures do not appear to persist beyond 6 months. Data on maintenance
treatments are sparse. Cupping refers to the application of suction on tender
musculotendinous areas via various devices. It is theorized to help relieve
inflammation. Wet cupping appears to decrease low back and neck pain. Patients
should be referred to appropriately credentialed clinicians. Health insurance
companies may not provide coverage for these therapies.
PMID- 29963847
TI - Multifunctional Yolk-Shell Mesoporous Silica Obtained via Selectively Etching the
Shell: A Therapeutic Nanoplatform for Cancer Therapy.
AB - Herein, we fabricated a new yolk-shell-structured mesoporous silica nanoparticle
(YMSN) with multifunctionalities of fluorescence imaging, photothermal therapy
(PTT), and drug delivery by using a fluorescein isothiocyanate-doped silica
nanoparticle partially covered by patchy gold as the core. Different from the
conventional selective etching procedure, the multifunctional silica core is left
intact, and the alkali etching mainly occurs in a hexadecyl trimethyl ammonium
bromide/silica hybrid layer, which leads to the formation of the void space in
YMSNs. In addition, the utilization of patchy gold as the PTT agent can avoid the
shield against the outer irradiation on the core. Results show that the as
prepared YMSNs have a good biocompatibility in the concentration of 0-1000 MUg.mL
1 and a high doxorubicin-loading capability (8.04 wt %). In vitro and in vivo
antitumor experiments reveal that the resulting YMSNs can be utilized for chemo-
and photothermic combination therapy as well as optical imaging.
PMID- 29963848
TI - Lipidomics Suggests a New Role for Ceramide Synthase in Phagocytosis.
AB - Phagocytosis is an evolutionarily conserved biological process where pathogens or
cellular debris are cleared by engulfing them in a membrane-enclosed cellular
compartment called the phagosome. The formation, maturation, and subsequent
degradation of a phagosome is an important immune response essential for
protection against many pathogens. Yet, the global lipid profile of phagosomes
remains unknown, especially as a function of their maturation in immune cells.
Here, we show using mass spectrometry based quantitative lipidomics that the
ceramide class of lipids, especially very long chain ceramides, are enriched on
maturing phagosomes with a concomitant decrease in the biosynthetic precursors of
ceramides. We thus posit a new function for the enzyme ceramide synthase during
phagocytosis in mammalian macrophages. Biochemical assays, cellular lipid feeding
experiments, and pharmacological blockade of ceramide synthase together show that
this enzyme indeed controls the flux of ceramides on maturing phagosomes. We also
find similar results in the primitive eukaryote Dictyostelium discoideum,
suggesting that ceramide enrichment may be evolutionarily conserved and likely an
indispensible step in phagosome maturation.
PMID- 29963849
TI - Electrochemical Degradation Mechanism and Thermal Behaviors of the Stored
LiNi0.5Co0.2Mn0.3O2 Cathode Materials.
AB - The degradation mechanism of the stored LiNi0.5Co0.2Mn0.3O2 (NCM523) electrode
has been systematically investigated by combining physical and electrochemical
tests. After stored at 55 degrees C and 80% relative humidity for 4 weeks, the
NCM523 materials are coated with a layer of impurities containing adsorbed
species, Li2CO3 and LiOH, resulting in both the weight gains of the materials and
the electrochemical performance deterioration of the electrode. The impurities
generated in air will react with the electrolyte and instantly turn into Li xPO
yF z and other species containing the decomposition products of electrolyte when
the stored NCM523 materials are soaked into the electrolyte, causing the charge
potential plateau and the impedance to ascend. For the stored NCM523 electrodes,
the huge and changeable impedance deteriorates the discharge capacity in the
first 10 cycles and the discharge capacity will slowly recover and stabilize
within 10 cycles when charging/discharging in 0.1 or 0.2 C. The thermal stability
of the stored NCM523 materials get slightly better due to the relatively lower
delithiated state after charged to 4.3 V.
PMID- 29963850
TI - Efficient and Versatile Pipet Microextraction Device Based on a Light-Heatable
Sorbent.
AB - Miniaturized sample pretreatment platforms have simplified analytical tasks in
diverse disciplines. Herein, a novel pipet microextraction (PME) device is
reported by making use of the photothermal property of a light-heatable sorbent
(LHS) for the first time. Efficient and staining-free heating treatment of small
volumes of liquids confined in the PME device is now enabled through light
illumination. The light-induced heating treatment is capable of dramatically
accelerating solvent elution rates, effectively unlocking bound toxin from its
antibody, and rapidly quenching enzymatic activities, thus, provides PME with
higher efficiencies and enables its new applications in antibody-intermediated
sampling of targeted toxin from stained food surfaces and powders, as well as in
accurate revelation of enzymatic reaction kinetics. This study offers a new
perspective of designing efficient and versatile microextraction platforms and
demonstrates their potential applications in different fields including public
security, new drug development, and environmental protection.
PMID- 29963851
TI - Liquids Unidirectional Transport on Dual-Scale Arrays.
AB - Liquids unidirectional transport has cutting-edge applications ranging from fog
collection, oil-water separation, to microfluidic devices. Despite extensive
progresses, existing man-made surfaces with asymmetric wettability or
micro/nanoscales structures are still limited by complex fabrication techniques
or obscure essential transport mechanisms to achieve unidirectional transport
with both high speeds and large volumes. Here, we demonstrate the three
dimensional printed micro/macro dual-scale arrays for rapid, spontaneous, and
continuous unidirectional transport. We reveal the essential directional
transport mechanism via a Laplace pressure driven theory. The relationship
between liquid unidirectional transport and surface morphology parameter is
systematically explored. Threshold values to achieve unidirectional transport are
determined. Significantly, dual-scale arrays even facilitate liquid's uphill
running, microfluidics patterning, and liquid shunting in target directions
without external energy input. Free combination of dual-scale island arrays
modules, just like LEGO bricks, achieves fast liquid transport on demand. This
dual-scale island array can be used to build smart laboratory-on-a-chip devices,
printable microfluidic integration systems, and advanced biochemistry
microreactors.
PMID- 29963852
TI - Spontaneously Blinking Fluorescent Protein for Simple Single Laser Super
Resolution Live Cell Imaging.
AB - Super-resolution imaging techniques based on single molecule localization
microscopy (SMLM) broke the diffraction limit of optical microscopy in living
samples with the aid of photoswitchable fluorescent probes and intricate
microscopy systems. Here, we developed a fluorescent protein, SPOON, which can be
switched off by excitation light illumination and switched on by thermally
induced dehydration, resulting in an apparent spontaneous blinking behavior. This
unique property of SPOON provides a simple SMLM-based super-resolution imaging
platform which requires only a single 488 nm laser.
PMID- 29963853
TI - Depth-Profiling Microanalysis of CoNCN Water-Oxidation Catalyst Using a lambda =
46.9 nm Plasma Laser for Nano-Ionization Mass Spectrometry.
AB - Nanoscale depth profiling analysis of a CoNCN-coated electrode for water
oxidation catalysis was carried out using table-top extreme ultraviolet (XUV)
laser ablation time-of-flight mass spectrometry. The self-developed laser
operates at lambda = 46.9 nm and represents factor of 4 reduction in wavelength
with respect to the 193 nm excimer laser. The reduction of the wavelength is an
alternative approach to the reduction of the pulse duration, to enhance the
ablation characteristics and obtain smaller quasi-nondestructive ablation pits.
Such a XUV-laser ablation method allowed distinguishing different composite
components of the catalyst-Nafion blend, used to modify a screen-printed carbon
electrode surface. Chemical information was extracted by fragment assignment and
relative amplitude analysis of the mass spectrometry peaks. Pure Nafion and the
exposed carbon substrate were compared as references. Material specific fragments
were clearly identified by the detected nonoverlapping mass-to-charge peaks of
Nafion and CoNCN. Three dimensional mapping of relevant mass peak amplitudes was
used to determine the lateral distribution and to generate depth profiles from
consecutive laser pulses. Evaluating the profiles of pristine electrodes gave
insight into fragmentation behavior of the catalyst in a functional ionomer
matrix and comparison of post-catalytic electrodes revealed spots of thin
localized Co residues.
PMID- 29963854
TI - Heavy Exposure of Waste Collectors to Polycyclic Aromatic Hydrocarbons in a Poor
Rural Area of Middle China.
AB - Manual collection and open-air incineration of waste materials is a common
practice in rural regions of China and beyond. Low-temperature combustion of
rubber and plastic waste generates high levels of airborne polycyclic aromatic
hydrocarbons (PAHs). We investigated ten urinary hydroxylated PAH metabolites (OH
PAHs), the oxidative damage biomarker (8-hydroxy-deoxyguanosine, 8-OHdG), and
four serum biomarkers including gamma-glutamyl transferase (GGT) and alanine
aminotransferase (ALT) in 41 waste collectors and 122 control subjects residing
in the same or a distant rural village in Henan Province. The level of PAH
metabolites in urine (median: 17.24 MUg/g Cre) was twice that of controls living
in the same area without an occupational history involving waste collection
(median: 8.16 MUg/g Cre) and thrice that of controls living 30 km away (median:
6.07 MUg/g Cre). The concentrations of OH-PAHs were positively associated with
urinary 8-OHdG levels (beta = 0.283, p < 0.05). Serum GGT and ALT were slightly
increased in waste collectors. Urinary 8-OHdG levels were similar in one-year and
longer-term workers, suggesting that rubber and plastic waste
collection/incineration carries a high PAH exposure risk. These data provide
solid baseline information, emphasizing the importance of monitoring the long
term health outcomes of waste collectors and changes in exposure patterns
associated with rural development and regulation of waste disposal.
PMID- 29963855
TI - Nanoliter-Scale Electromembrane Extraction and Enrichment in a Microfluidic Chip.
AB - This paper reports for the first time nanoliter-scale electromembrane extraction
(nanoliter-scale EME) in a microfluidic device. Six basic drug substances (model
analytes) were extracted from 70 MUL samples of human whole blood, plasma, or
urine through a supported liquid membrane (SLM) of 2-nitrophenyl octyl ether
(NPOE) and into 6 nL of 10 mM formic acid as an acceptor solution. A DC potential
of 15 V was applied across the SLM and served as the driving force for the
extraction. The cathode was located in the acceptor solution. Because of the
small area of the SLM (0.06 mm2), the system provided soft extraction with
recoveries <1% for the 70 MUL samples. Because of the large sample-to-acceptor
volume ratio, analytes were enriched in the acceptor solution. The enrichment
capacity was 6-7-fold per minute, and after 60 min of operation, most of the
model analytes were enriched by a factor of approximately 400. Because of the SLM
and the direction of the applied electrical field, substantial sample cleanup was
obtained. The chips were based on thiol-ene polymers, and the soft-lithography
fabrication procedure and the materials were selected in such a way that future
mass production should be feasible. The chip-to-chip variability was within 23%
RSD (and less than 10% in most cases) with respect to extraction recovery. Our
findings have verified that nanoliter-scale EME is highly feasible and provides
reliable data, and for future studies, the concept should be tested for
applicability in connection with in vitro microphysiological systems, organ-on-a
chip systems, and point-of-care diagnostics. These are potential areas where the
combination of soft extraction and high enrichment from limited sample volumes is
required for reliable analytical measurements.
PMID- 29963856
TI - Electrochemical Arylation Reaction.
AB - Arylated products are found in various fields of chemistry and represent
essential entities for many applications. Therefore, the formation of this
structural feature represents a central issue of contemporary organic synthesis.
By the action of electricity the necessity of leaving groups, metal catalysts,
stoichiometric oxidizers, or reducing agents can be omitted in part or even
completely. The replacement of conventional reagents by sustainable electricity
not only will be environmentally benign but also allows significant short cuts in
electrochemical synthesis. In addition, this methodology can be considered as
inherently safe. The current survey is organized in cathodic and anodic
conversions as well as by the number of leaving groups being involved. In some
electroconversions the reagents used are regenerated at the electrode, whereas in
other electrotransformations free radical sequences are exploited to afford a
highly sustainable process. The electrochemical formation of the aryl-substrate
bond is discussed for aromatic substrates, heterocycles, other multiple bond
systems, and even at saturated carbon substrates. This survey covers most of the
seminal work and the advances of the past two decades in this area.
PMID- 29963857
TI - Covalency is Frustrating: La2Sn2O7 and the Nature of Bonding in Pyrochlores under
High Pressure-Temperature Conditions.
AB - Natural specimens of the pyrochlore (A2B2O7) compounds have been found to retain
foreign actinide impurities within their parent framework, undergoing
metamictization to a fully amorphous state. The response to radionuclide decay
identifies pyrochlore systems with having high radiation tolerance and tailored
use in radioactive waste applications and radionuclide sequestration. High
pressure is a powerful pathway to high density states and amorphization with
parallels to radiation-induced processes. Here, La2Sn2O7 is evaluated under
extreme conditions via the combination of laser heating in a diamond anvil cell
with X-ray diffraction and Raman spectroscopy. The measurements are supported by
ab initio random structure searching and molecular dynamics calculations. A new
ground state at 70 GPa is revealed, and high temperature annealing is fundamental
to access its crystalline ground state and fully determine the structure. This
crystalline phase ( P21/ c) retains its structural integrity during decompression
and is fully recoverable to ambient conditions. The final state of the system is
shown to be highly pathway dependent due to the covalent nature of the Sn-O
bonding. The Tc pyrochlore, La2Tc2O7, is analyzed for similarities in the bonding
to determine the likelihood of an analogous pathway dependency to a final state.
PMID- 29963858
TI - Self-Assembled Double-Bundle DNA Tetrahedron for Efficient Antisense Delivery.
AB - DNA nanostructures are promising biomaterials capable of arranging multiple
functional components with nanometer precision. Here, a double-bundle DNA
tetrahedron is rationally designed to integrate with antisense oligonucleotides
silencing proto-oncogene c-raf and nuclear targeting peptides. The functionalized
DNA tetrahedron can be internalized by A549 cells and assists the delivery of
antisense oligonucleotides toward the nucleus to increase the chance to
downregulate target mRNA in nucleus and cytoplasm. Antisense strands released
from the tetrahedron in response to the intracellular reducing environment can
inhibit cell proliferation at a low concentration without transfection reagent.
Finally, efficient knockdown of c-raf gene is observed, which verified our
design. This designer DNA-based nanocarrier system will open a new avenue for
efficient delivery of nucleic acid drugs.
PMID- 29963859
TI - Paclitaxel-Loaded Self-Assembled Lipid Nanoparticles as Targeted Drug Delivery
Systems for the Treatment of Aggressive Ovarian Cancer.
AB - Chemotherapy using cytotoxic agents, such as paclitaxel (PTX), is one of the most
effective treatments for advanced ovarian cancer. However, due to nonspecific
targeting of the drug and the presence of toxic solvents required for dissolving
PTX prior to injection, there are several serious side effects associated with
this treatment. In this study, we explored self-assembled lipid-based
nanoparticles as PTX carriers, which were able to improve its antitumour efficacy
against ovarian cancer. The nanoparticles were also functionalized with epidermal
growth factor receptor (EGFR) antibody fragments to explore the benefit of tumor
active targeting. The formulated bicontinuous cubic- and sponge-phase
nanoparticles, which were stabilized by Pluronic F127 and a lipid poly(ethylene
glycol) stabilizer, showed a high capacity of PTX loading. These PTX-loaded
nanoparticles also showed significantly higher cytotoxicity than a free drug
formulation against HEY ovarian cancer cell lines in vitro. More importantly, the
nanoparticle-based PTX treatments, with or without EGFR targeting, reduced the
tumor burden by 50% compared to PTX or nondrug control in an ovarian cancer mouse
xenograft model. In addition, the PTX-loaded nanoparticles were able to extend
the survival of the treatment groups by up to 10 days compared to groups
receiving free PTX or nondrug control. This proof-of-concept study has
demonstrated the potential of these self-assembled lipid nanomaterials as
effective drug delivery nanocarriers for poorly soluble chemotherapeutics, such
as PTX.
PMID- 29963860
TI - Gold Nanoparticles Bearing a Tumor pH-Sensitive Cyclodextrin Cap.
AB - We report functional gold nanoparticles (AuNPs) with a pH-sensitive gamma
cyclodextrin (CD) cap. These particles include two chargeable CD molecules on
their surface. CD with dopamine and amine (NH2) groups (hereafter termed as dCD
NH2) was anchored to the gold surface and then electrostatically complexed with
the CD with 2,3-dimethylmaleic acid (DMA) and chlorin e6 (Ce6) (hereafter termed
as cCD-DMA), producing an ionic complex consisting of dCD-NH2 and cCD-DMA. Under
the acidic environment (pH 6.8) existing in most solid tumors, the ionic complex
was destabilized because of the decoupling of DMA, resulting in the release of
cCD (without DMA) from the AuNPs, resulting in extensive tumoral uptake of AuNPs
with dCD-NH2 (because of their electrostatic attraction to tumor cells). This
event resulted in a significant increase in the efficiency of cellular AuNP
uptake and light-driven (AuNP-mediated photothermal and Ce6-mediated
photodynamic) ablation of acidic solid tumors, suggesting marked potential for
tumor therapy.
PMID- 29963861
TI - Encapsulation-Free Stabilization of Few-Layer Black Phosphorus.
AB - Under ambient conditions and in H2O and O2 environments, reactive oxygen species
(ROS) cause immediate degradation of the mobility of few-layer black phosphorus
(FLBP). Here, we show that FLBP degradation can be prevented by maintaining the
temperature in the range ~125-300 degrees C during ROS exposure. FLBP devices
maintained at elevated temperature show no deterioration of electrical
conductance, in contrast to the immediate degradation of pristine FLBP held at
room temperature. Our results constitute the first demonstration of stable FLBP
in the presence of ROS without requiring encapsulation or a protective coating.
The stabilization method will enable applications based on the surface properties
of intrinsic FLBP.
PMID- 29963862
TI - Direct Molten Polymerization Synthesis of Highly Active Samarium Manganese
Perovskites with Different Morphologies for VOC Removal.
AB - A morphology-controlled molten polymerization route was developed to synthesize
SmMnO3 (SMO) perovskite catalysts with netlike (SMO-N), granular-like (SMO-G),
and bulk (SMO-B) structures. The SMO perovskites were formed directly by a molten
polymerization method, and their morphologies were controlled by using the
derivative polymers as templates. Among all catalysts, the porous SMO-N exhibited
the highest activity, over which the toluene, benzene, and o-xylene were
completely oxidized to CO2 at 240, 270, and 300 degrees C, respectively, which
was comparable to that of typical noble-metal catalysts. The apparent activation
energies of toluene over SMO-N (56.4 kJ.mol-1) was much lower than that of SMO-G
(70.8 kJ.mol-1) and SMO-B (90.1 kJ.mol-1). Based on the results of scanning
electron microscopy, transmission electron microscopy, X-ray photoelectron
spectroscopy, and H2 temperature-programmed reduction characterization, we deduce
that the excellent removal efficiency of volatile organic compounds (VOCs) over
SMO-N catalyst was attributable to the special structure, high surface Mn4+/Mn3+
and Olatt/Oads molar ratios, and strong reducibility. Due to the high activity,
low cost, and simple preparation strategy, the SMO catalyst is a promising
catalyst for VOC removal.
PMID- 29963863
TI - In Vivo Photoacoustic Detection and Imaging of Peroxynitrite.
AB - Photoacoustic detection is an emerging noninvasive and nonionizing detection
technique with the merits of rich contrast, high resolution, and deep tissue
penetration, especially for in vivo detection and imaging. Herein, we developed a
photoacoustic (PA) molecular imaging probe (denoted as nanonaps) composed of a
naphthalocyanine dye and a heptamethine dye as the internal standard with
unchanged signals at 860 nm and the sensing component with peroxynitrite (ONOO-)
target-decreased signals at 775 nm, respectively. The as-prepared nanonaps
displayed high sensitivity and specificity of ONOO- both in vitro and in vivo.
The PA860/PA775 ratio was increased as a function of the concentration of ONOO-
(0-250 nM). More interestingly, our ratiometric nanonaps could be used for in
vivo detection and imaging of ONOO-.
PMID- 29963864
TI - Adjusting the Structure of 2'-Modified Nucleosides and Oligonucleotides via C4'
alpha-F or C4'-alpha-OMe Substitution: Synthesis and Conformational Analysis.
AB - We report the first syntheses of three nucleoside analogues, namely, 2',4'-diOMe
rU, 2'-OMe,4'-F-rU, and 2'-F,4'-OMe-araU, via stereoselective introduction of
fluorine or methoxy functionalities at the C4'-alpha-position of a 4',5'-olefinic
intermediate. Conformational analyses of these nucleosides and comparison to
other previously reported 2',4'-disubstituted nucleoside analogues make it
possible to evaluate the effect of fluorine and methoxy substitution on the sugar
pucker, as assessed by NMR, X-ray diffraction, and computational methods. We
found that C4'-alpha-F/OMe substituents reinforce the C3'-endo ( north)
conformation of 2'-OMe-rU. Furthermore, the predominant C2'-endo ( south/ east)
conformation of 2'-F-araU switches to C3'-endo upon introduction of these
substituents at C4'. The nucleoside analogues were incorporated into DNA and RNA
oligonucleotides via standard phosphoramidite chemistry, and their effects on the
thermal stability of homo- and heteroduplexes were assessed via UV thermal
melting experiments. We found that 4'-substituents can modulate the binding
affinity of the parent 2'-modified oligomers, inducing a mildly destabilizing or
stabilizing effect depending on the duplex type. This study expands the spectrum
of oligonucleotide modifications available for rational design of oligonucleotide
therapeutics.
PMID- 29963865
TI - Equilibration Dependence of Fucoxanthin S1 and ICT Signatures on Polarity,
Proticity, and Temperature by Multipulse Femtosecond Absorption Spectroscopy.
AB - To demonstrate the value of the multipulse method in revealing the nature of
coupling between excited states and explore the environmental dependencies of
lowest excited singlet state (S1) and intramolecular charge transfer (ICT) state
equilibration, we performed ultrafast transient absorption pump-dump-probe and
pump-repump-probe spectroscopies on fucoxanthin in various solvent conditions.
The effects of polarity, proticity, and temperature were tested in solvents
methanol at 293 and 190 K, acetonitrile, and isopropanol. We show that
manipulation of the kinetic traces can produce one trace reflecting the
equilibration kinetics of the states, which reveals that lower polarity,
proticity, and temperature delay S1/ICT equilibration. On the basis of a two
state model representing the S1 and ICT states on the same S1/ICT potential
energy surface, we were able to show that the kinetics are strictly dependent on
the initial relative populations of the states as well as the decay of the ICT
state to the ground state. Informed by global analysis, a systematic method for
target analysis based on this model allowed us to quantify the population
transfer rates throughout the life of the S1/ICT state as well as separate the S1
and ICT spectral signatures. The results are consistent with the concept that the
S1 and ICT states are part of one potential energy surface.
PMID- 29963866
TI - Palladium-Catalyzed Reductive Conversion of Acyl Fluorides via Ligand-Controlled
Decarbonylation.
AB - Ligand-controlled non-decarbonylative and decarbonylative conversions of acyl
fluorides were developed using a Pd(OAc)2/Et3SiH combination. When
tricyclohexylphosphine (PCy3) was used as the ligand, aldehydes were obtained as
simple reductive conversion products. The use of 1,2
bis(dicyclohexylphosphino)ethane (Cy2P(CH2)2PCy2, DCPE) as the ligand, however,
favored the formation of hydrocarbons, which are decarbonylative reduction
products.
PMID- 29963867
TI - Thermochemistry and Kinetic Studies on the Autoignition of 2-Butanone: A
Computational Study.
AB - Unimolecular reactions of alkylperoxy(ROO*), hydroperoxyalkyl(*QOOH), and
hydroperoxyalkylperoxy(*OOQOOH) radicals of 2-butanone, which is a potential
biofuel molecule, have been studied computationally. These radicals are
responsible for the chain branching at low temperature oxidation and play a
significant role in modeling the autoignition. The composite CBS-QB3 method was
used to study the thermochemistry and energetics of all the species involved.
Intrinsic reaction coordinate (IRC) calculations were carried out for all the
transition states along various reaction pathways. All the possible reactions
like H-migration, *OH elimination, and HO*2 elimination reactions were studied
for these radicals. It was found that, the isomerization of *OOQOOH to HOOQOO* is
the most favorable channel, which involves 8- and 9-membered cyclic transition
states. However, the decomposition pathway involves the H-migration from carbon
to oxygen. The mechanism for the decomposition of all *OOQOOH radicals with their
potential energy level diagrams are reported. The temperature dependent rate
coefficients were also studied using Canonical Variational Transition state
theory (CVT) with small curvature tunneling (SCT) in the temperature range of 400
1500 K, which is relevant to the combustion. Thermodynamic parameters for all the
reactions involved were calculated. The high barrier (1,3 H-migration) reactions
were found to be exothermic and spontaneous, which is unexpected.
PMID- 29963868
TI - Phloroglucinol Derivatives with Unusual Skeletons from Cleistocalyx operculatus
and Their in Vitro Antiviral Activity.
AB - Four novel phloroglucinol derivatives (1-4) featuring a 2,4-dimethyl-cinnamyl
phloroglucinol moiety, along with their putative biosynthetic precursors 5 and 6,
were isolated from the leaves of Cleistocalyx operculatus. Compounds 1 and 2 are
two pairs of new enantiomeric phloroglucinol dimers possessing an unprecedented
polycyclic skeleton with a highly functionalized dihydropyrano[3,2- d]xanthene
tetracyclic core. Compounds 3 and 4 are two new phloroglucinol-terpene adducts
(PTAs) with a novel carbon skeleton. The structures of 1-4 including their
absolute configurations were unambiguously accomplished by combination of
extensive spectroscopic analyses, X-ray crystallography, and quantum chemical ECD
calculations. A hypothetical biosynthetic pathway for 1-4 was also proposed.
Compound 1 exhibited a promising in vitro antiherpes simplex virus type-1 (HSV-1)
effect.
PMID- 29963869
TI - Metal-Free Electrophilic Trifluoroethylthiolation with NaSO2CH2CF3.
AB - Metal-free trifluoroethylthiolation with fluorinated sulfinate salt NaSO2CH2CF3
under reductive conditions has been developed. The strategy enables the
installation of the SCH2CF3 moiety efficiently to form a number of unexplored
stable trifluoroethylthiolated heterocycles, arenes, and thiols, which have the
potential to be a new series of fluorine-containing chemical entities for
medicinal chemists.
PMID- 29963870
TI - Metal-Free Etherification of Aryl Methyl Ether Derivatives by C-OMe Bond
Cleavage.
AB - A general and efficient protocol was developed for the synthesis of aryl alkyl
ethers through metal-free C-OMe bond cleavage under mild reaction conditions.
This process displays a wide scope of methoxyarenes and alcohols, including
primary, secondary, and tertiary alcohols, as well as natural products,
pharmaceuticals, and biologically active alcohols. DFT calculations and
experimental results simultaneously confirm that a potassium ion plays a critical
role in the activation of methoxy group via binding with the nitrile and provide
support for an SNAr mechanism.
PMID- 29963871
TI - 2-Diazoacetyl-2 H-azirines: Source of a Variety of 2 H-Azirine Building Blocks
with Orthogonal and Domino Reactivity.
AB - A synthesis of 2-diazoacetyl-2 H-azirines was developed starting from 2 H-azirine
2-carbonyl chlorides, generated by Fe(II)-catalyzed isomerization of 5
chloroisoxazoles. 2-Diazoacetyl-2 H-azirines easily undergo reactions
characteristic of alpha-diazo ketones with preservation of the azirine ring.
Reactions with hydrohalogenic, carboxylic, and p-toluenesulfonic acids provide
novel 1-(3-aryl-2 H-azirin-2-yl)-2-halo- and 2-(R-oxy)ethan-1-ones in good
yields. The synthesized 2 H-azirines can offer many possibilities for chemical
manipulation in heterocyclic synthesis, due to the presence of highly reactive
azirine and the exocyclic C(O)-CHN2 or C(O)-CH2X functionalities, which can show
orthogonal or domino reactivity. The synthetic usefulness of the developed
building blocks was demonstrated by the preparation of new types of heterocyclic
dyads (azirine-oxazole, azirine-pyrazoline, azirine-thiazole, azirine-oxirane,
pyrrole-oxazole) as well as an azirine chalcone analogue, 2-azidoacetyl-2 H
azirine, and 2-diazoacetylaziridine derivatives.
PMID- 29963872
TI - Limited modulation of the abuse-related behavioral effects of d-methamphetamine
by disulfiram.
AB - Disulfiram (Antabuse), an acetaldehyde dehydrogenase and dopamine-beta
hydroxylase inhibitor, has shown promise in preclinical and clinical studies as a
pharmacotherapy for cocaine addiction. However, the extent to which disulfiram
may alter the abuse-related behavioral effects of related psychostimulants, such
as methamphetamine, is unknown. Here, the therapeutic potential of disulfiram was
evaluated by examining its impact on the reinforcing and discriminative stimulus
effects of d-methamphetamine in adult rhesus monkeys (N = 4 per group). In
subjects trained to respond for injections of methamphetamine or food delivery,
i.v. methamphetamine (.001-.032 mg/kg) maintained dose-related and stable levels
of self-administration in all subjects. Pretreatment with disulfiram (5.6 mg/kg)
produced a significant downward shift in the d-methamphetamine dose-response
function; surprisingly, lower and higher pretreatment doses (3.0 mg/kg; 10 mg/kg)
were ineffective. Also, disulfiram (3-10 mg/kg) did not significantly alter food
maintained responding or, in subjects trained to discriminate the effects of
cocaine from vehicle, the ability of d-methamphetamine (.032-.32 mg/kg) to
substitute for cocaine. Taken together, the present data reveal dose-dependent
effects of disulfiram in modifying some of the abuse-related effects of d
methamphetamine and provides support for future investigations examining the
capacity of disulfiram as a treatment for d-methamphetamine abuse. (PsycINFO
Database Record (c) 2018 APA, all rights reserved).
PMID- 29963873
TI - Boring thoughts and bored minds: The MAC model of boredom and cognitive
engagement.
AB - What is boredom? We review environmental, attentional, and functional theories
and present a new model that describes boredom as an affective indicator of
unsuccessful attentional engagement in valued goal-congruent activity. According
to the Meaning and Attentional Components (MAC) model, boredom is the result of
(a) an attentional component, namely mismatches between cognitive demands and
available mental resources, and (b) a meaning component, namely mismatches
between activities and valued goals (or the absence of valued goals altogether).
We present empirical support for four novel predictions made by the model: (a)
Deficits in attention and meaning each produce boredom independently of the
other; (b) there are different profiles of boredom that result from specific
deficits in attention and meaning; (c) boredom results from two types of
attentional deficits, understimulation and overstimulation; and (d) the model
explains not only when and why people become bored with external activities, but
also when and why people become bored with their own thoughts. We discuss further
implications of the model, such as when boredom motivates people to seek
interesting versus enjoyable activities. (PsycINFO Database Record (c) 2018 APA,
all rights reserved).
PMID- 29963874
TI - Reciprocal relations between positive alcohol expectancies and peer use on
adolescent drinking: An accelerated autoregressive cross-lagged model using the
NCANDA sample.
AB - Positive alcohol expectancies (PAE) and associating with drinking peers are
reliable predictors of adolescent alcohol use. Knowledge of when and for whom
these risk factors are most influential could enhance intervention effectiveness.
Reciprocal relations between PAE and adolescent and peer alcohol use were
examined between the ages of 13 and 18 in a sample (N = 566; 50% female) from the
National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), as
well as sex differences in these associations. Associating with drinking peers
prospectively predicted more frequent alcohol use for both sexes, although peer
socialization was evident earlier for girls compared with boys. Higher PAE
influenced later drinking in mid-adolescence, from age 14 to 16, for boys only.
PAE influenced peer group selection for both sexes, although the influence was
evident earlier in boys than girls. The relative impact of environmental risk
factors for problematic alcohol use may vary over time and across developmental
periods. These results suggest that prevention and treatment efforts for
adolescent drinking can be improved by targeting age-appropriate risk factors.
Early adolescent interventions may be best served by minimizing involvement with
drinking peers and correcting normative beliefs of peer use. Among adolescent
girls, early interventions focused on reducing peer influence may be most
effective. Prevention and treatment programs aimed at addressing PAE would likely
prove more effective for boys in mid- to late adolescence. (PsycINFO Database
Record
PMID- 29963876
TI - Moderation of improvement in self-efficacy following group psychotherapy for
PTSD.
AB - Posttraumatic stress disorder (PTSD) is a primary mental health concern of
veterans. In clinical settings, efforts to improve broad facets beyond symptom
amelioration and consideration of moderators of treatment effectiveness in this
population are needed for continued improvement in care. General self-efficacy
(GSE) has been indicated as a useful treatment target because of its association
with positive outcomes such as increased positive health behaviors. Both race and
educational attainment represent potential moderators of treatment response that
are relevant for a veteran PTSD population. This study aimed to determine whether
a PTSD Recovery Group Therapy Program resulted in improvement in GSE and whether
racial and educational differences moderated GSE outcomes. Archival data were
examined from male veterans (N = 450) receiving mental health services at a
Veterans Affairs medical center using multilevel modeling to examine change in
GSE over the course of treatment as well as moderation of change in GSE as a
function of race and educational attainment. After completion of group therapy,
results indicated there was significant improvement in GSE, with significantly
different improvement based on education. Higher levels of education were
associated with greater increases in GSE after treatment. Improvement in GSE did
not differ by participant race. In clinical settings, efforts to increase GSE and
attending to moderators such as educational attainment may be useful for
improving PTSD treatment approaches. (PsycINFO Database Record
PMID- 29963875
TI - Nonacute effects of cannabis use on motivation and reward sensitivity in humans:
A systematic review.
AB - Reduced motivation is often noted as a consequence of cannabis use. However,
prior studies examining this association have suboptimally operationalized
motivation and have yielded mixed findings. This review discusses motivation and
the closely related construct of reward sensitivity. We summarize the available
literature examining associations between motivation and cannabis use, addressing
the following questions: (a) Is there evidence for decreased motivation among
cannabis users? (b) Is there evidence that lack of motivation among cannabis
users is specific to their use of cannabis (rather than to use of other addictive
drugs)? and (c) Is there evidence suggesting a causal relationship between
cannabis use and motivation? Using PubMed, PsycINFO, and WebofScience, we
conducted a literature search of studies examining nonacute effects of cannabis
use on motivation, apathy, amotivation, effort, and reward sensitivity in humans.
This search yielded 22 studies, which were reviewed in detail. We conclude that,
although cross-sectional evidence of a cannabis-specific effect on motivation is
equivocal, there is partial support from longitudinal studies for a causal link
between cannabis use and reduced motivation. Additionally, we propose that reward
sensitivity and motivation represent distinct yet related constructs and that
reductions in one may not always lead to reductions in the other. Future work
should longitudinally examine associations between cannabis use, motivation, and
reward sensitivity; carefully define and operationalize these constructs; and
control for the influence of potential confounding factors. (PsycINFO Database
Record
PMID- 29963877
TI - The presumption of guilt in suspect interrogations: Apprehension as a trigger of
confirmation bias and debiasing techniques.
AB - This research tests whether a police officer's decision to apprehend a suspect
triggers confirmation bias during an interrogation. The study also tests two
strategies to reduce confirmation bias: (1) decoupling decision to apprehend from
interrogation and (2) reducing cognitive load for the interrogating police
officer. In Experiment 1, Swedish police officers (N = 60) were faced with 12
scenarios in which they either had to decide for themselves whether to apprehend
a suspect or were informed about the corresponding decision by another police
officer or a prosecutor. Participants then prepared questions for a suspect
interrogation and evaluated the trustworthiness of the suspect's denial or
confession. The same method was used in Experiment 2 but with law and psychology
students (N = 60) as participants. In Experiment 3, psychology students (N = 60)
prepared interrogation questions either by freely producing their own or by
choosing questions from a preset list. Overall, apprehended suspects were
interrogated in a more guilt presumptive way and rated as less trustworthy than
non apprehended suspects. However, the tested debiasing techniques, primarily
reducing cognitive load for the interrogating police officer, hold some potential
in mitigating this bias. (PsycINFO Database Record
PMID- 29963878
TI - "The family that prays together . . .": Relational processes associated with
regular family prayer.
AB - In the present article we explored how family prayer reportedly influenced family
relationships. We conceptualized family prayer as a family ritual in religious
families and used a qualitative methodology to interview a religiously,
ethnically, and geographically diverse sample of 198 families (N = 476). Analysis
of data revealed 7 related themes. Family prayer served important functions and
influenced relationships in various ways including (a) as a time of family
togetherness and interaction; (b) as a space for social support; and (c) as a
means for intergenerational transmission of religion. Further, family prayer (d)
involved issues and concerns of individuals and the family; (e) helped reduce
relational tensions; (f) provided feelings of connectedness, unity, and bonding.
Finally, (g) families struggled to pray together when there was disunity.
Implications, applications, and future directions are addressed. (PsycINFO
Database Record (c) 2018 APA, all rights reserved).
PMID- 29963879
TI - Semantic measures: Using natural language processing to measure, differentiate,
and describe psychological constructs.
AB - Psychological constructs, such as emotions, thoughts, and attitudes are often
measured by asking individuals to reply to questions using closed-ended numerical
rating scales. However, when asking people about their state of mind in a natural
context ("How are you?"), we receive open-ended answers using words ("Fine and
happy!") and not closed-ended answers using numbers ("7") or categories ("A
lot"). Nevertheless, to date it has been difficult to objectively quantify
responses to open-ended questions. We develop an approach using open-ended
questions in which the responses are analyzed using natural language processing
(Latent Semantic Analyses). This approach of using open-ended, semantic questions
is compared with traditional rating scales in nine studies (N = 92-854),
including two different study paradigms. The first paradigm requires participants
to describe psychological aspects of external stimuli (facial expressions) and
the second paradigm involves asking participants to report their subjective well
being and mental health problems. The results demonstrate that the approach using
semantic questions yields good statistical properties with competitive, or
higher, validity and reliability compared with corresponding numerical rating
scales. As these semantic measures are based on natural language and measure,
differentiate, and describe psychological constructs, they have the potential of
complementing and extending traditional rating scales. (PsycINFO Database Record
PMID- 29963880
TI - Massage can (re-)activate the lower limb sensorimotor representation of older
adult inpatients.
AB - Understanding how changes in afferent signal processing may impact the
sensorimotor processes is essential for physical therapists whose objective is to
actively improve the reorganization of motor function in patients suffering from
sensorimotor system disturbance. Because the sensorimotor processes are slowed
with the advance in age, we examined whether a single massage session can
reactivate the sensorimotor processes of older adult inpatients. Participants
were randomly assigned to the experimental (with massage) or control (without
massage) groups. Massage was realized on both feet with 7.30 min spent on each
foot (Experiment 1), the right foot or the right foot and knee for 10 min
(Experiment 2). Body and nonbody mental rotation tasks were used to assess the
lower limb motor representation before (pretest), immediately after (Posttest 1)
and 24 hr after the massage (Posttest 2). Results showed the positive impact of
massage on the body mental rotation task. The activation of the sensorimotor
processes can last up to 24 hr depending on the extent of the massaged area.
Importantly, the activation of the sensorimotor representation concerned not only
the massaged leg but also the contralateral leg. No difference between groups
appeared in the nonbody mental rotation task which did not solicit the
sensorimotor processes. These results highlighted that peripheral activation via
a massage had a specific impact on the sensorimotor processes. Massage is an
interesting technique which can help older adult inpatients cope with the
slowdown of the signal processing related to advancing age. (PsycINFO Database
Record
PMID- 29963882
TI - Explicit versus actionable knowledge: The influence of explaining graphical
conventions on interpretation of hurricane forecast visualizations.
AB - Visualizations of uncertainty in data are often presented to the public without
explanations of their graphical conventions and are often misunderstood by
nonexperts. The "cone of uncertainty" used to visualize hurricane forecasts is a
case in point. Here we examined the effects of explaining graphical conventions
on understanding of the cone of uncertainty. In two experiments, participants
were given instructions with and without an explanation of these graphical
conventions. We examined the effect of these instructions on both explicit
statements of common misconceptions and users interpretation of hurricane
forecasts, specifically their predictions of damage from the hurricane over space
and time. Enhanced instructions reduced misconceptions about the cone of
uncertainty as expressed in explicit beliefs, and in one experiment also reduced
predictions of damage overall. Examination of individual response profiles for
the damage estimate task revealed qualitative differences between individuals
that were not evident in aggregate response profiles. This research reveals mixed
results for the effectiveness of instructions on comprehension of uncertainty
visualizations and suggests a more nuanced approach that focuses on the
individual's knowledge and beliefs about the domain and visualization. (PsycINFO
Database Record
PMID- 29963881
TI - Ethnic minority community therapists' acculturation and reported adaptations to
children's evidence-based practices.
AB - OBJECTIVE: This study examined associations between ethnic minority therapists'
reports of acculturation and adaptations made to multiple evidence-based
practices (EBPs) in children's community mental health services. Multilevel
modeling was used to analyze therapist- and practice-level predictors of
Augmenting and Reducing/Reordering adaptations, the two subscales of the
Adaptations to Evidence-Based Practices Scale (AES; Lau et al., 2017). METHOD: An
online survey was completed by 235 therapists (86% women, Mage = 34.82 years,
68.1% Hispanic/Latino) as part of a larger study examining EBP sustainment in Los
Angeles County, California. Acculturation was measured through therapist reports
of cultural identity and language use using the Abbreviated Multidimensional
Acculturation Scale (Zea, Asner-Self, Birman, & Buki, 2003). RESULTS: Analyses
showed that the effect of Heritage Cultural Identity on Augmenting adaptations
was moderated by Heritage Language Use. There was a significant interaction
between Heritage and United States Cultural Identity dimensions in predicting
Reducing/Reordering adaptations. Therapists who reported higher levels of
Heritage Cultural Identity and lower levels of United States Cultural Identity
reported the fewest Reducing/Reordering adaptations, whereas therapists who
reported higher levels of affiliation with both their Heritage Culture and United
States Culture reported making the most Reducing/Reordering adaptations. Language
acculturation and other cultural factors such as Ethnicity and Generational
Status did not predict either adaptation type. Therapists who reported more
favorable perceptions of the EBP reported making fewer Reducing/Reordering
adaptations. CONCLUSION: Findings suggest that cultural identity is linked to the
likelihood that ethnic minority therapists may adapt EBPs. (PsycINFO Database
Record (c) 2018 APA, all rights reserved).
PMID- 29963883
TI - Conjoint recognition procedures reveal verbatim processing enhances memory for
emotionally valenced pictorial stimuli.
AB - Frequently, emotion is associated with enhancements in memory as long as arousal
is not too extreme. Negative valence can also lead to increased false memories.
Yet less is known about specific memory processes that drive these effects of
emotional content on memory performance. The present study uses conjoint
recognition analyses to investigate the memory processes associated with memory
for negative and positive pictorial stimuli. Participants studied pictures, which
had been rated as negative-arousing, positive-arousing, or neutral-non-arousing,
before completing a recognition memory test 48 hr later. Contrary to initial
expectations based on process-based estimates of emotional words, gist-based
processing did not lead to high levels of true memory for negative pictures, nor
were negative pictures associated with compellingly real false memories. Instead,
negative pictures were recognized more frequently than neutral pictures, and this
effect was related to increased verbatim-based identity judgments. However,
emotional memory enhancements were not observed for positive pictures. These
results indicate that emotional memory enhancements for negative pictures are
related to enhanced verbatim processing of emotional material. When false
memories did occur for negative pictures, they were because of gist-based
similarity judgments as predicted by prior process-based estimates of false
memory for negative-arousing words or pictures. Such results are discussed in
terms of eyewitness memory and the processes underlying such remembering, because
in many criminal and forensically relevant situations, witnesses, who are often
victims as well, are asked to recognize the perpetrator or other arousing aspects
of an event. (PsycINFO Database Record
PMID- 29963884
TI - Intergroup emotional exchange: Ingroup guilt and outgroup anger increase resource
allocation in trust games.
AB - Intergroup exchanges are an integral part of social life but are compromised when
one group pursues its interests at another group's expense. The present research
investigates whether expressing emotion can mitigate the negative consequences of
such actions. We examine how emotions communicated by either an ingroup or
outgroup member following an ingroup member's breach of trust affect other
ingroup members' feelings of guilt and pride, and subsequent allocation of
resources. In both studies, groups of participants played a two-round trust game
with another group. In round one, they observed a member of their own group
failing to reciprocate a trusting move by the outgroup. In Study 1 (N = 85), an
outgroup member then communicated anger or disappointment, whereas in Study 2 (N
= 164), an ingroup member then communicated happiness or guilt. Comparisons with
no-emotion control conditions revealed that expressions of outgroup anger and
ingroup guilt increased participants' allocations to an outgroup member in round
two. The effect of an outgroup member's anger expression was mediated by
participants' diminished feelings of pride about the ingroup action, whereas the
effect of an ingroup member's guilt expression was mediated by participants' own
feelings of guilt. Taken together, these findings support a social appraisal
approach and highlight the roles that pride and guilt can play in shaping
intergroup resource allocations. (PsycINFO Database Record
PMID- 29963885
TI - Timing is crucial for the integration of angry facial expressions with motor
responses: Investigation of subliminal and supraliminal emotion-action bindings.
AB - Our brain codes perceptual features and actions in a distributed fashion, causing
a binding problem: How does the brain recognize that information pertains to a
specific object and not to other concurrently processed objects? Hommel (1998)
suggested the event file concept: An episodic memory trace binding perceptual
features and actions related to an event. By adapting Hommel's paradigm to
emotional faces in a previous series of studies (Coll & Grandjean, 2016), we
revealed that emotion could take part in an event file with motor responses when
emotion is task relevant and in specific situations when emotion is task
irrelevant. In the latter case, we supposed that such integration occurs because
of the importance of emotion-action coupling for our survival, even when the task
is not specifically related to emotion. To date, emotion-action binding has been
studied only with faces presented for 500 ms. In continuation with the hypothesis
that humans developed adaptive mechanisms to allow fast responses to emotions, we
designed 2 experiments to investigate the influence of the duration of angry and
neutral face presentation on binding with motor responses. Results showed that
emotion-action integration was possible in a 100-, 250-, and 500-ms presentation,
but not when the faces were subliminally (14 ms) or supraliminally (28 ms)
displayed. Timing is crucial in emotion-action binding, and although reaction to
emotional stimuli might take place rapidly, its integration, as shown by the
present studies, seems to require at least 100 ms. (PsycINFO Database Record
PMID- 29963886
TI - Who smiles while alone? Rates of smiling lower in China than U.S.
AB - Previous studies have found that Westerners value high intensity positive
emotions more than people in China and Japan, yet few studies have compared
actual rates of smiling across cultures. Particularly rare are observational
studies of real-time smiling (as opposed to smiling in photos). In Study 1,
raters coded student ID photos of European American and East Asian students in
the U.S. In Study 2, observers coded people's smiles as they walked outside in
the U.S. and China. Both studies found that people from East Asia smiled much
less-about 50% less. These differences could reflect differences in happiness
across cultures, norms of smiling, or differences in ideal affect. (PsycINFO
Database Record
PMID- 29963887
TI - Visual-tactile selective attention in autism spectrum condition: An increased
influence of visual distractors.
AB - We have previously observed that participants with autism spectrum condition
(ASC) are more influenced by visual distractors during a tactile task compared
with controls (Poole, Gowen, Warren, & Poliakoff, 2015). This finding suggests
that changes in multisensory processing could underpin differences in sensory
reactivity in ASC. Here we explore the cognitive mechanisms underlying this
effect. Adults with ASC (n = 22) and matched neurotypical (NT) controls (n = 22)
completed 3 tasks involving similar stimuli. In Experiment 1, we again showed
that when participants with ASC were performing a tactile task they were
distracted more by visual stimuli compared with NTs. In Experiment 2, however, no
differences between the groups were observed on an alternative visual-tactile
task (temporal order judgment) requiring attention to both the stimuli. That is,
ASC performance was typical when the task did not require the visual stimuli to
be suppressed. Furthermore, in Experiment 3 the effects of visual distractors
were comparable between the groups when the tactile target was replaced with a
visual target. When comparing performance across Experiments 1 and 3, NT
participants were better able to suppress visual distractors when the target was
tactile than when the target was visual (Experiment 1 vs. 3), but this crossmodal
benefit was not observed in participants with ASC. The effects of visual
distractors were comparable regardless of the target modality suggesting that the
efficacy of visual-tactile selective attention may be reduced in ASC. (PsycINFO
Database Record
PMID- 29963888
TI - Gaze-based signatures of mind wandering during real-world scene processing.
AB - Physiological limitations on the visual system require gaze to move from location
to location to extract the most relevant information within a scene. Therefore,
gaze provides a real-time index of the information-processing priorities of the
visual system. We investigated gaze allocation during mind wandering (MW), a
state where cognitive priorities shift from processing task-relevant external
stimuli (i.e., the visual world) to task-irrelevant internal thoughts. In both a
main study and a replication, we recorded the eye movements of college-aged
adults who studied images of urban scenes and responded to pseudorandom thought
probes on whether they were mind wandering or attentively viewing at the time of
the probe. Probe-caught MW was associated with fewer and longer fixations,
greater fixation dispersion, and more frequent eyeblinks (only observed in the
main study) relative to periods of attentive scene viewing. These findings
demonstrate that gaze indices typically considered to represent greater
engagement with scene processing (e.g., longer fixations) can also indicate MW.
In this way, the current work exhibits a need for empirical investigations and
computational models of gaze control to account for MW for a more accurate
representation of the moment-to-moment information-processing priorities of the
visual system. (PsycINFO Database Record
PMID- 29963889
TI - Contributing factors predicting nightmares in children: Trauma, anxiety,
dissociation, and emotion regulation.
AB - OBJECTIVE: There is little research in the current literature regarding
contributing factors to nightmares in children. This study aimed to test
potentially overlapping predictors of nightmare distress and severity, including
anxiety, dissociation, trauma history, vagal tone, and parental processing of
emotions. METHOD: Sixty parent-child dyads (children ages 6-11) filled out a
variety of child-report and parent-observation inventories on nightmare frequency
and distress, dissociation, anxiety, and trauma history of the child. Children
were monitored on heart rate variability and vagal tone. Both parent and child
participated in a discussion of positive and negative life events that were later
coded for degree of parent processing of emotional information. RESULTS: Anxiety,
trauma history, dissociation, and baseline vagal tone accounted for 39% of the
variance in nightmare distress. Anxiety and dissociation were positive predictors
of nightmare distress in the multiple regression. Parent processing variables
were weak predictors in the current analysis. CONCLUSIONS: The predictive power
of anxiety, dissociation, vagal tone, and trauma history was not entirely due to
their overlap, as shown by uniquely significant beta weights in the prediction of
distress. Treatment procedures with multiple intervention points targeting
physiological and psychological sources of nightmare distress may be warranted.
(PsycINFO Database Record
PMID- 29963890
TI - Comorbid mood and anxiety disorders and severity of posttraumatic stress disorder
symptoms in treatment-seeking veterans.
AB - OBJECTIVE: Comorbidity is the rule and not the exception among veterans with
posttraumatic stress disorder (PTSD). Examining comorbidities in a veteran
population allows us to better understand veterans' symptoms and recognize when
mental health treatment may need to be tailored to other co-occurring issues.
This article evaluates comorbid mood and anxiety disorders and PTSD symptom
severity in a large sample of veterans from multiple eras of service, including
the recent wars in Iraq and Afghanistan. METHOD: The current study used data from
veterans who sought treatment for PTSD at a VA PTSD Clinical Team from 2005 to
2013. Veterans were assessed for PTSD, mood, and anxiety disorders using a
structured clinical interview and completed self-report symptom measures as part
of the PTSD clinic intake procedure. A total of 2,460 veterans were evaluated,
and 867 met diagnostic criteria for PTSD. RESULTS: Veterans with PTSD were
significantly more likely than those without PTSD to be diagnosed with social
anxiety disorder and obsessive-compulsive disorder, but significantly less likely
to be diagnosed with depression. In addition, veterans who had at least one
comorbid diagnosis in addition to PTSD reported significantly higher PTSD symptom
severity than veterans with PTSD alone. PTSD symptom severity also varied by era
of service. CONCLUSION: These results suggest that among veterans seeking
treatment for PTSD, comorbid mood and anxiety disorders may be associated with
greater severity of PTSD symptoms. Future work is needed to determine the impact
of specific comorbidities on trauma-focused treatment outcomes. (PsycINFO
Database Record
PMID- 29963891
TI - Killing during combat and negative mental health and substance use outcomes among
recent-era veterans: The mediating effects of rumination.
AB - OBJECTIVE: Although killing in combat is associated with negative mental health
outcomes and hazardous alcohol use, mechanisms that underlie this risk are not
well understood. To our knowledge, this present brief report is the first to use
mediation analysis to examine associations between killing in combat, distinct
facets of rumination (problem-focused thoughts, counterfactual thinking,
repetitive thoughts, and anticipatory thoughts), and negative mental health
outcomes (i.e., depression, anxiety, PTSD, suicidality) and hazardous alcohol
use. METHOD: Participants were a community sample of 283 military personnel (158
males [60.31%]; mean age = 32.61 [SD = 7.11]) who had deployed in support of
recent wars in Iraq or Afghanistan. Participants completed an online self-report
survey. RESULTS: Three rumination facets (i.e., problem-focused thoughts,
counterfactual thinking, and anticipatory thoughts) uniquely (controlling for
effects of other rumination facets) mediated the associations between killing in
combat and negative mental health outcomes and hazardous alcohol use. Taken
together, killing in combat was associated with higher levels of each rumination
facet, which in turn were distinctly associated with more negative symptoms of
mental health and more hazardous drinking (problem-focused thoughts were the only
facet to mediate all effects). Beyond these significant mediation effects,
killing in combat still had a significant direct effect on every outcome.
CONCLUSION: These findings provide preliminary support for associations between
killing in combat and negative mental health outcomes and hazardous alcohol use.
Furthermore, rumination (particularly problem-focused thoughts) may be an
important consideration in the evaluation and care of recent-era combat veterans.
(PsycINFO Database Record
PMID- 29963892
TI - Residual symptoms following empirically supported treatment for PTSD.
AB - OBJECTIVE: Although there are several evidence-based treatments that are
effective in mitigating the symptoms of posttraumatic stress disorder (PTSD),
rates of nonresponse to treatment as well as treatment dropout remain high. In
order to determine which symptoms remain most problematic at the end of treatment
for PTSD, the present study examined residual symptoms in a treatment study that
evaluated the effects of cognitive processing therapy (CPT) and prolonged
exposure (PE). METHOD: The sample consisted of 108 female rape survivors who
initially met criteria for PTSD and who were then randomized into and completed
either CPT or PE. The sample was 71% White and 25% African American, with an
average age of 32 years (SD = 9.98 years). RESULTS: Symptoms of PTSD, depression,
guilt, and social adjustment were evaluated in the sample of treatment
completers, and findings suggest that overall symptoms improved over the course
of treatment. Results further suggested that distress related to trauma
reminders, detachment, and insomnia were the most common residual PTSD symptoms
at posttreatment, while self-blame, concerns about body image, and fatigue were
the most common residual symptoms of depression. The most common residual symptom
of guilt was lack of justification for actions that had to be taken during the
index event. CONCLUSIONS: This pattern of findings is in line with past research
suggesting that evidence-based practices are effective in the treatment of PTSD,
but underscores the need to continue to evaluate residual symptoms to best assist
clients in achieving full recovery. (PsycINFO Database Record
PMID- 29963893
TI - Motivating job characteristics and happiness at work: A multilevel perspective.
AB - Employees may react differently to the perceived availability of motivating job
characteristics during work activities, depending on the degree to which such
motivating job characteristics are also present at the job level and individual
differences. This study expands Job Characteristics Theory (JCT) by using a
multilevel approach to predict how variations in motivating job characteristics
relate to employee happiness during daily work activities. Based on adaptation
level theory and the affective-reactivity hypothesis, we predicted that the
positive relationship between perceived motivating job characteristics and
happiness during work activities is moderated by motivating job characteristics
at the job level and individual differences in trait positive affect. A sample of
68 employees filled out a general survey and reported on their job
characteristics and happiness during 741 work activities using a day
reconstruction method across five working days. In line with adaptation level
theory, multilevel results confirmed that the perceived availability of
motivating job characteristics during work activities relates positively to
happiness during that same work activity, but only when similar motivating job
characteristics at the job level are low. In addition, trait positive affect
further moderated this cross-level interaction. In line with the affective
reactivity hypothesis, the 3-way interaction effect showed that for employees who
are high in positive affect, the perceived availability of motivating job
characteristics related positively to happiness during specific work activities,
regardless of whether similar motivating job characteristics at the job level
were high or low. We discuss how these findings add important temporal dynamics
to JCT. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
PMID- 29963894
TI - Worthy of swift trust? How brief interpersonal contact affects trust accuracy.
AB - Organizational scholars have long underscored the positive consequences of trust,
yet trust can also have dysfunctional effects if it is not placed wisely. Though
much research has examined conditions that increase individuals' tendencies to
trust others, we know very little about the circumstances under which individuals
are likely to make more accurate trust decisions (i.e., neither misplace their
trust nor refrain from trusting when doing so would have been beneficial),
especially when they must do so rapidly and in the absence of an exchange
history. Put simply, we have little understanding of what drives the accuracy of
swift trust judgments. Building on relevant literatures, we propose that short
episodes of prior interpersonal contact with a partner can increase the accuracy
of swift trust decisions. Across two experimental studies, we demonstrate that
brief interpersonal contact leads trustors to both (a) become more accurate in
their trust decisions; and (b) engage in other-focused perspective taking, which
mediates the effect of interpersonal contact on trust accuracy. We then show that
it is specifically because of verbal cues, rather than visual cues, that brief
interpersonal contact enables other-focused perspective taking, and in turn,
trust accuracy (Study 3). We contribute to the literature on trust by examining
trust accuracy (rather than mere trust levels), identifying the significant role
of brief interpersonal contact, and revealing other-focused perspective taking as
a key mechanism in accurate swift trust decisions. (PsycINFO Database Record (c)
2018 APA, all rights reserved).
PMID- 29963895
TI - Sprinting to the finish: Toward a theory of Human Capital Resource
Complementarity.
AB - In traditional work contexts, factors such as individuals' general competencies
are used to predict indices of their performance such as yearly performance
appraisals. Whereas traditional approaches to predicting individuals' performance
focus on differences between individuals, a considerable proportion of
variability in performance is attributable to within-person sources. However, we
submit that within-person variability in performance may also be attributable to
the fact that people work in different contexts. Moreover, individual performance
is often the result of unrecognized team contributions. Accordingly, we advance a
Human Capital Resource Complementarity (HCRC) theory to explain the alignment of
human capital resources with dynamic situational features, and to illustrate the
influence of team collective competencies on the performance of individual
members. We then empirically test HCRC theory-derived hypotheses using a sample
of 169 cyclists from 22 teams across 18 stages of the centennial Tour de France.
Our results suggest that individuals' specific competencies interact with
situational characteristics to predict their performance variability over time,
beyond that accounted for by their general competencies. Moreover, these effects
are accentuated to the extent that teammates' competencies aligned with
individual competencies in a given situation. Implications for future theory
building, research, and practice are discussed. (PsycINFO Database Record (c)
2018 APA, all rights reserved).
PMID- 29963896
TI - On the pursuit of multiple goals with different deadlines.
AB - This article presents a theory of how people prioritize their time when pursuing
goals with different deadlines. Although progress has been made in understanding
the dynamics of multiple-goal pursuit, theory in this area only addresses cases
where the goals have the same deadline. We rectify this issue by integrating the
multiple-goal pursuit model-a formal theory of multiple goal pursuit-with
theories of intertemporal motivation and choice. We examine the ability of four
computational models derived from this general theory to account for
participants' choices across four experiments. The models make different
assumptions about how people determine the valence of prioritizing a goal (i.e.,
by monitoring distance to goal or time pressure), and whether the goal is subject
to temporal discounting. In each experiment, participants performed a task
requiring them to pursue two goals. Experiments 1 and 2 manipulated deadline and
distance; Experiment 3 manipulated deadline and time pressure; Experiment 4
manipulated all three factors. Counter to the predictions of existing theory,
participants generally prioritized the goal with the shorter deadline. We also
observed weak, but positive effects of distance on prioritization (Experiment 2)
and nonlinear effects of time pressure (Experiment 3). The model that best
explained participants' decisions assumed that valence is determined by time
pressure and the expected utility of a goal is subject to temporal discounting.
This new model broadens the range of phenomena that can be accounted for within a
single theory of multiple-goal pursuit, and improves our understanding of the
interface between motivation and decision making. (PsycINFO Database Record (c)
2018 APA, all rights reserved).
PMID- 29963897
TI - Workplace ostracism and employee creativity: An integrative approach
incorporating pragmatic and engagement roles.
AB - Extending an extant dynamic componential perspective, we propose an integrative
model of how and why workplace ostracism exhibited by supervisors relates to
employees' creativity through pragmatic (task resources) and engagement (creative
process engagement) effects. Specifically, we predict that workplace ostracism
negatively relates to creativity through reduced task resources and creative
process engagement. Perceived organizational support plays a key role in
buffering the negative effects of workplace ostracism in both pragmatic and
engagement domains. Three-wave, supervisor-subordinate, dyadic data from a bank
in China support these hypotheses. We discuss the implications of these results
for both research and practice. (PsycINFO Database Record (c) 2018 APA, all
rights reserved).
PMID- 29963898
TI - Central tendency and matched difference approaches for assessing interrater
agreement.
AB - In Study 1 of this two-part investigation, we present a "central tendency
approach" and procedures for assessing overall interrater agreement across
multiple groups. We define parameters for mean group agreement and construct
bootstrapped confidence intervals around the mean population parameters for rWG,
AD, and ICC(1). In Study 2, we extend assessments of overall interrater agreement
by developing a "matched difference approach" and procedures for assessing real
versus pseudo agreement in a sample of groups. Here, we use random group
resampling and the matched difference between assessments of the respective rWG,
AD, and ICC(1) values for actual and pseudo groups, with the establishment of
bootstrapped confidence intervals around such differences. In both studies, we
employ simulated and real data to demonstrate the accuracy and practical utility
of the new procedures for assessing agreement with respect to groups. Notably, to
generate simulated data for Studies 1 and 2, we developed a new underlying model
for multilevel data and procedure for data generation, and we discuss its
potential utility for enhancing research in group-level studies. Moreover, we
discuss, relative to current practices, how and why the new inference procedures
provide information about mean interrater agreement in the population, which can
improve data aggregation decisions and interpretations of findings from group
level studies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
PMID- 29963899
TI - A New Transport Solution for Parathyroid Allotransplantation: Effects on Cell
Viability and Calcium-Sensing Receptors.
AB - BACKGROUND: Cold ischemia protects organs and tissues by slowing their
metabolism, but it also causes ischemic injury. Minimizing cold ischemia has been
an important goal in parathyroid auto- and allotransplantation, as well as the
transplantation of other major organs. Parathyroid glands are responsible for
calcium homeostasis by releasing parathormone (PTH) into the blood circulation.
Functionality of a new parathyroid transport solution (NPTS) and effects on cell
viability, PTH secretion, and calcium-sensing receptor (CaSR) levels during cold
ischemia were evaluated. MATERIALS AND METHODS: A NPTS was prepared, and the pH
was adjusted to a range of 7.2-7.4 and kept at +4 degrees C until use. Seven
patients with parathyroid hyperplasia secondary to chronic renal failure who were
scheduled to undergo subtotal parathyroidectomy were enrolled in the study.
Glands were cold-preserved in NPTS with different time intervals (0, 6, 12, 18,
and 24 hours), and then parathyroid cell viability before and after
cryopreservation, PTH secretion, and CaSR levels were determined. RESULTS: The
mean cell viability before cryopreservation was 92.7% (range 89.2%-97.2%). There
were no significant differences in cell viability rates before and after
cryopreservation (p = 0.1168 and p = 0.4085, respectively), and CaSR levels (p =
0.5446) were not significant. CONCLUSIONS: NPTS is a solution designed
specifically for parathyroid tissue transplantation. This patent pending product
can support cellular viability and PTH release, as well as protect CaSR
functionality for up to 24 hours of cold ischemia.
PMID- 29963900
TI - A Novel Method for Assessing the Statistical Significance of RNA-RNA Interactions
Between Two Long RNAs.
AB - RNA-RNA interactions are key mechanisms through which noncoding RNA (ncRNA)
regions exert biological functions. Computational prediction of RNA-RNA
interactions is an essential method for detecting novel RNA-RNA interactions
because their comprehensive detection by biological experimentation is still
quite difficult. Many RNA-RNA interaction prediction tools have been developed,
but they tend to produce many false positives. Accordingly, assessment of the
statistical significance of computationally predicted interactions is an
important task. However, there is no method to evaluate the statistical
significance of RNA-RNA interactions that is applicable to interactions between
two long RNA sequences. We developed a method to calculate the p-value for the
minimal interaction energy between two long RNA sequences. The developed method
depends on the fact that minimum interaction energies of RNA-RNA interactions
between long RNAs follow a Gumbel distribution when repeat sequences in RNAs are
masked. To show the usefulness of the developed method, we applied it to whole
human 5'-untranslated region (UTR) and 3'-UTR sequences to detect novel 5'-UTR-3'
UTR interactions. We thus identified two significant 5'-UTR-3'-UTR interactions.
Specifically, the human small proline-rich repeat protein 3 shows conserved 5'
UTR-3'-UTR interactions with some nucleotide variations preserving base pairings
among primates. Our developed method enables us to detect statistically
significant RNA-RNA interactions between long RNAs such as long ncRNAs.
Statistical significance estimates help in identification of interactions for
experimental validation and provide novel insights into the function of ncRNA
regions.
PMID- 29963901
TI - Investigation of GHSR and GHRL methylation in colorectal cancer.
AB - AIM: To investigate GHSR and GHRL methylation in 73 pairs of colorectal cancer
(CRC) tissues and healthy adjacent mucosa. METHODS: Methylation was assessed with
methylation-sensitive high-resolution melting. RESULTS: GHSR was significantly
hypermethylated in CRC tissues than in healthy mucosa (p < 1 * 10-5), but no
significant changes of GHRL methylation were observed. GHSR hypermethylation was
already detectable at the adenoma stage and maintained in later stages
independently of age, gender, anatomical location, histological grading, MLH1
deficiency, as well as of major polymorphisms in folate-pathway genes, yielding
an area under the curve of 0.824 for discriminating cancers from respective non
neoplastic mucosa specimens. CONCLUSION: GHSR hypermethylation occurs early in
CRC, but is not paralleled by significant changes of GHRL methylation.
PMID- 29963902
TI - A Cross Talk Between BRG1 and Males Absent on the First Contributes to Reactive
Oxygen Species Production in a Mouse Model of Nonalcoholic Steatohepatitis.
AB - AIMS: Accumulation of reactive oxygen species (ROS) in hepatocytes in response to
excessive nutrients and the ensuing liver damages caused by ROS constitute a key
pathophysiological event in nonalcoholic steatohepatitis (NASH). In the present
study, we investigated the epigenetic mechanism underlying ROS production in NASH
pathogenesis. RESULTS: NASH was induced by feeding the mice with a methionine-and
choline-deficient (MCD) diet for 4 weeks. Compared with the control mice (wild
type [WT]), mice with hepatocyte-specific deletion of Brg1 (HepcKO), a core
component of the mammalian chromatin remodeling complex, developed a less severe
form of NASH when fed on the MCD diet. Importantly, ROS levels were attenuated in
HepcKO mice as opposed to WT mice. Brahma-related gene 1 (Brg1) deficiency
downregulated the transcription of NADPH oxidases (NOX1, NOX2, and NOX4) both in
vivo and in vitro. Mechanistically, Brg1 deletion rendered a more repressive
chromatin structure surrounding the NOX promoters as characterized by reduced
levels of acetylated histones. In addition, Brg1 interacted with the histone
H4K16 acetyltransferase males absent on the first (MOF) to activate NOX
transcription. MOF knockdown by small interfering RNA or pharmaceutical
inhibition by MG149 suppressed NOX transcription and ameliorated ROS levels.
INNOVATION: Our data highlight a novel epigenetic mechanism through which Brg1
and MOF cooperate to regulate ROS production in hepatocytes in response to pro
NASH stimuli. CONCLUSION: A cross talk between Brg1 and MOF epigenetically
activates NOX transcription and elevates ROS synthesis contributing to NASH
pathogenesis. Antioxid. Redox Signal. 00, 000-000.
PMID- 29963903
TI - Addendum to Pulmonary ground-glass nodules diagnosis: mean change rate of peak CT
number as a discriminative factor of pathology during a follow-up Br J Radiol
2016; 89/1058.
PMID- 29963905
TI - The Natural History of Full-Thickness Rotator Cuff Tears in Randomized Controlled
Trials: A Systematic Review and Meta-analysis.
AB - BACKGROUND: Rotator cuff tears are the most common tendon injury in the adult
population, resulting in substantial morbidity. The optimum management for these
patients is not known. PURPOSE: To assess the overall treatment response to all
interventions in full-thickness rotator cuff tears among patients enrolled in
randomized clinical trials. STUDY DESIGN: Systematic review and meta-analysis.
METHODS: Randomized controlled trials (RCTs) were identified from a systematic
search of Medline, Embase, CINHAL, and the Cochrane Central Register of
Controlled Trials. Patients were aged >=18 years with a full-thickness rotator
cuff tear. The primary outcome measure was change in Constant shoulder score from
baseline to 52 weeks. A meta-analysis to assess treatment response was calculated
via the standardized mean change in scores. RESULTS: A total of 57 RCTs were
included. The pooled standardized mean change as compared with baseline was 1.42
(95% CI, 0.80-2.04) at 3 months, 2.73 (95% CI, 1.06-4.40) at 6 months, and 3.18
(95% CI, 1.64-4.71) at 12 months. Graphic plots of treatment response
demonstrated a sustained improvement in outcomes in nonoperative trial arms and
all operative subgroup arms. CONCLUSION: Patients with full-thickness rotator
cuff tears demonstrated a consistent pattern of improvement in Constant score
with nonoperative and operative care. The natural history of patients with
rotator cuff tears included in RCTs is to improve over time, whether treated
operatively or nonoperatively.
PMID- 29963904
TI - Active Scapular Retraction and Acromiohumeral Distance at Various Degrees of
Shoulder Abduction.
AB - CONTEXT: Performing shoulder-abduction exercises with scapular retraction has
been theorized to reduce the potential for shoulder impingement. However,
objective data to support this premise are lacking. OBJECTIVE: To evaluate the
influence of active scapular retraction on acromiohumeral distance (AHD) at 4
shoulder-abduction angles using real-time ultrasound. DESIGN: Cross-sectional
study. SETTING: University laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty
asymptomatic individuals (10 men, 10 women; age = 22.9 +/- 2.8 years, height =
169.3 +/- 9.5 cm, mass = 65.5 +/- 12.9 kg) were recruited. MAIN OUTCOME
MEASURE(S): Real-time ultrasound images of AHD were obtained during
nonretracted and retracted scapular conditions at 0 degrees , 45 degrees , 60
degrees , and 90 degrees of shoulder abduction. A 2-factor analysis of variance
with repeated measures was used to evaluate the influence of shoulder retraction
on AHD across shoulder-abduction angles. RESULTS: A scapular-retraction
condition * shoulder-abduction-angle interaction for AHD was found ( F3,57 =
4.56, P = .006). The AHD was smaller at 0 degrees (10.5 versus 11.2 mm,
respectively; t19 = 2.22, P = .04) but larger at 90 degrees (9.4 versus 8.7 mm,
respectively; t19 = -2.30, P = .04) of shoulder abduction during the retracted
than the nonretracted condition. No differences in AHD were observed between
conditions at 45 degrees ( t19 = 1.45, P = .16) and 60 degrees ( t19 = 1.17, P
= .86) of abduction. CONCLUSIONS: The observed differences in AHD at 0 degrees
and 90 degrees of shoulder abduction were small and did not exceed the
established minimal detectable change for either angle. Our findings suggest that
active scapular retraction during shoulder abduction has a minimal influence on
AHD at 0 degrees and 90 degrees in healthy individuals. Further investigations
are needed to determine whether scapular retraction influences AHD in individuals
with subacromial impingement.
PMID- 29963906
TI - Cytokine gene transcription in the trachea, Harderian gland, and trigeminal
ganglia of chickens inoculated with virulent infectious laryngotracheitis virus
(ILTV) strain.
AB - The objective of this study was to determine how cytokine transcription profiles
correlate with patterns of infectious laryngotracheitis virus (ILTV) replication
in the trachea, Harderian gland, and trigeminal ganglia during the early and late
stages of infection after intratracheal inoculation. Viral genomes and
transcripts were detected in the trachea and Harderian gland but not in
trigeminal ganglia. The onset of viral replication in the trachea was detected at
day one post-infection and peaked by day three post-infection. The peak of pro
inflammatory (CXCLi2, IL-1beta, IFN-gamma) and anti-inflammatory (IL-13, IL-10)
cytokine gene transcription, 5 days post-infection, coincided with the increased
recruitment of inflammatory cells, extensive tissue damage, and limiting of virus
replication in the trachea. In contrast, transcription of the IFN-beta gene in
the trachea remained unaffected suggesting that ILTV infection blocks type I
interferon responses. In the Harderian gland, the most evident transcription
change was the early and transient upregulation of the IFN-gamma gene at 1 day
post-infection, which suggests that the Harderian gland is prepared to rapidly
respond to ILTV infection. Overall, results from this study suggest that
regulation of Th1 effector cells and macrophage activity by Th1/2 cytokines was
pertinent to maintain a balanced immune response capable of providing an adequate
Th1-mediated protective immunity, while sustaining some immune homeostasis in
preparation for the regeneration of the tracheal mucosa.
PMID- 29963907
TI - Seroprevalence of Borrelia burgdorferi in forest workers from inspectorates with
different forest types in Lower Silesia, SW Poland: preliminary study.
AB - To estimate the Lyme borreliosis (LB) risk for forest workers, totally 646 blood
samples were tested for IgG and IgM anti-Borrelia burgdorferi s.l. (anti-B.b.)
antibody occurrence using ELISA tests confirmed with western blot. To clarify the
varied LB risk, additionally, the data from the Forest Data Bank determining the
detailed forest habitat type in particular forest inspectorates were used. The
occurrence of the anti-B.b. antibody was confirmed in 22% (8.7% IgM, 17.8% IgG)
of forest workers. Analysis of the influence of the habitat type (forest types)
indicated the significant positive impact of the occurrence of the deciduous and
mixed-deciduous forests on the seroprevalence of anti-B.b. IgG level among
forestry workers. However, the share of forest type cannot be the only factor
taken into account when assessing risk.
PMID- 29963908
TI - Association of ADSL gene polymorphisms with meat quality and carcass traits in
domestic pigeons (Columba livia).
AB - 1. Adenylosuccinate lyase (ADSL) plays an important role in the synthesis of
inosine monophosphate (IMP). In this trial, a total of 200 pigeons were sampled
and slaughtered. Seven meat quality traits and 11 carcass traits were measured.
DNA sequencing was used to detect nucleotide mutations, and associations between
ADSL gene polymorphisms and meat quality and carcass traits were analysed. 2.
Sequencing results showed that 9 nucleotide mutations were found in the exons of
the ADSL gene. All the mutations were synonymous except C13065G, which caused a
change in amino acids (Ser to Arg). In addition, two of the detected single
nucleotide polymorphisms (SNPs) had significant associations with meat quality
and carcass traits. 3. For the C13065G SNP located in exon11, the IMP content of
breast muscle in AA and AB genotype was higher than in the BB genotype (P <
0.01). The SNP G10696A located in exon10 was significantly associated with
carcass rate, in which AA and AB genotype were higher than the BB genotype (P <
0.01). 4. The results indicated that the ADSL gene has a close association with
meat quality and carcass traits in domestic pigeons, and G10696A and C13065G SNPs
could be applied as genetic markers in molecular marker-assisted breeding of
pigeons.
PMID- 29963909
TI - Association of air quality with respiratory and cardiovascular morbidity rate in
Delhi, India.
AB - : The present study reports short-term impact of poor air quality on
cardiovascular and respiratory morbidity rate in Delhi. The data on monthly count
of patients visiting Out Patient Department (OPD) and hospital admission due to
respiratory and cardiovascular illnesses from hospitals along with daily air
quality data from air quality monitoring stations of Central Pollution Control
Board (CPCB), Government of India, across Delhi were collected for the period
2008 to 2012. A semi-parametric Quasi-Poisson regression model was used to
examine the association of high pollution episodes with relative risk of hospital
OPD visit and hospital admission due to respiratory and cardiovascular diseases.
This study has confirmed the substantial adverse health effects due to air
pollution across criterion air pollutants. The study reports the short-term
effects of air pollution on morbidity from a time-series study first time in
India. The study findings illustrate the evidence of adverse health impact of air
pollution from India to the global pool and can influence the policy makers to
implement better air quality management system for Indian cities. ABBREVIATIONS:
OPD: Out Patient Department; IPD: Inpatient Department; RD: Respiratory Disease;
CVD: Cardiovascular Disease; COPD: Chronic Obstructive Pulmonary Disease; CPCB:
Central Pollution Control Board; NAAQMP: National Ambient Air Quality Monitoring
Programme; NAAQS: National Ambient Air Quality Standards; RR; Relative Risk; IMD:
Indian Meteorological Department; PM10: Particulate Matter less than 10 MUm in
aerodynamic diameter; SO2: Sulphur dioxide; NO2: Nitrogen dioxide; CO: Carbon
Monoxide; O3: Ozone; DCE: Delhi College of Engineering; GTB Hospital: Guru Teg
Bahadur Hospital; VPCH: Vallabhbhai Patel Chest Hospital; RMLH: Ram Manohar Lohia
Hospital; SJH: Safdarjung Hospital; LNJPH: Lok Narayan Jai Prakash Hospital;
GTBH: Guru Teg Bahadur Hospital; AH: Ambedkar Hospital; HRH: Hindu Rao Hospital;
ESIH: ESI Hospital; SGRH: Sir Ganga Ram Hospital.
PMID- 29963910
TI - Response to letter to the editor titled "Do we really need to reconsider
coligranulomatosis (Hjarre & Wramby's disease) in poultry?"
PMID- 29963911
TI - Prediction of Rare Palmitoylation Events in Proteins.
AB - Palmitoylation directs many cellular processes such as protein trafficking,
sorting, signaling, interactions with other biomolecules, to name a few.
Palmitoylation commonly occurs on cysteine; however, occasional palmitoylation of
few other amino acids has also been reported. To date, comprehensive analysis on
occasional palmitoylation is unavailable. In the present study, we reported a
computational method to predict palmitoylation of glycine and serine residues in
a protein. The method is based on support vector machine (SVM). It was trained on
position-specific scoring matrix of amino acids that surrounds palmitoylated
glycine and serine. During training, SVM models were evaluated on leave-one-out
cross validation, and the maximum prediction accuracies achieved during training
were 100% glycine palmitoylation and 99.94% for serine palmitoylation. Similar
prediction for performance was also shown on independent data sets. The two SVM
models were used to develop a prediction method called RAREPalm. We provide web
server and standalone of RAREPalm, using the user that can predict the potential
glycine and serine palmitoylation site(s) in a protein. Comparative analysis of
glycine, serine, and cysteine palmitoylation was also done to analyze pathways
and classes to which different forms of palmitoylation belong. We hope that our
attempt will be useful in finding more glycine and serine that may undergo
palmitoylation and expanding the information on these lesser known sites of
palmitoylation.
PMID- 29963912
TI - Technique: open lumbar decompression and fusion with the Excelsius GPS robot.
AB - The Excelsius GPS (Globus Medical, Inc.) was approved by the FDA in 2017. This
novel robot allows for real-time intraoperative imaging, registration, and direct
screw insertion through a rigid external arm-without the need for interspinous
clamps or K-wires. The authors present one of the first operative cases utilizing
the Excelsius GPS robotic system in spinal surgery. A 75-year-old man presented
with severe lower back pain and left leg radiculopathy. He had previously
undergone 3 decompressive surgeries from L3 to L5, with evidence of instability
and loss of sagittal balance. Robotic assistance was utilized to perform a
revision decompression with instrumented fusion from L3 to S1. The usage of
robotic assistance in spinal surgery may be an invaluable resource in minimally
invasive cases, minimizing the need for fluoroscopy, or in those with abnormal
anatomical landmarks. The video can be found here: https://youtu.be/yVI-sJWf9Iw .
PMID- 29963913
TI - Robot-assisted resection of pre-sacral schwannoma.
AB - Resection of a giant pre-sacral schwannoma originating from the right S2 nerve in
a 22-year-old woman illustrates the potential for robotic surgery. The da Vinci
Robot Surgical System facilitates visualization deep in the pelvis and allows for
bimanual wristed instrument control to dissect the tumor from surrounding
sensitive structures. Neurostimulation to identify critical nerves is possible
and complete resection of the tumor can be achieved. There were no complications,
she remained neurologically intact, the estimated blood loss was less than 75 ml,
the total hospital stay was 3 days, and she returned to work within 2 weeks of
her operation. In select patients, robot-assisted surgery may have advantages.
The video can be found here: https://youtu.be/SYjUA-WcyGI .
PMID- 29963914
TI - Integrating robotics into a minimally invasive transforaminal interbody fusion
workflow.
AB - Minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) is a well
accepted procedure with good outcomes. Robotics has the potential to augment
these outcomes. This video demonstrates and discusses how surgeons can implement
the use of a robotic device in an MIS TLIF workflow. The planning software and
robotic arm guidance allow the surgeon to use intraoperative CT to guide the
placement of pedicle screws in an MIS TLIF with optimal trajectory and decreased
radiation. As robotic technology continues to improve, developing safe workflows
that integrate robotics with currently well-established techniques should improve
patient outcomes. The video can be found here: https://youtu.be/rJWOa6XVLW0 .
PMID- 29963915
TI - Navigated robotic assisted thoracic pedicle screw placement for metastatic renal
cell carcinoma.
AB - A 63-year-old man presented with progressive lower-extremity paresis over the
previous 3 months. He had been unable to support himself to ambulate over the
previous 3 weeks. The patient was found to have metastatic renal cell carcinoma
to T11. He underwent robotic assisted percutaneous placement of T9-L1 pedicle
screws and open T11 laminectomy/debulking of tumor. This approach allowed for
decreased blood loss without the need for preoperative embolization. After
decompression and placement of the hardware, the patient regained the ability to
ambulate on his own. The video can be found here: https://youtu.be/BTFQezhZlB4 .
PMID- 29963916
TI - Introduction: the rise of the robots in spinal surgery.
AB - In his 1920 science fiction play R.U.R., Czech writer Karel Capek introduced the
word "robot" to the English language. The play tells the story of a factory that
produces roboti, which are living creatures that resemble humans and have the
capacity for individual thought. While at first the roboti seem content to work
for their human masters, they later rebel, ultimately leading to the extinction
of the human race. 1 This play and similar depictions of robots in literature and
film are probably responsible for the slightly negative reputation of robots in
general. Only recently has this perception changed, thanks to the advent of
robots that can vacuum our houses and perform other mundane chores. Raymond
Goertz, while working for the US Atomic Energy Commission, is credited with the
development of the first robotic arm in 1951. 2 It was designed to handle
hazardous radioactive material. Unimation Inc. developed the first industrial
robot in 1961; that robot handled molten die-castings and removed the human
element from these labor-intensive, often dangerous tasks. With the development
of the Programmable Universal Manipulation Arm (PUMA) in 1978, the robot was
sophisticated enough to be introduced to medicine. The first working definition
of the word "robot" was published, fittingly, by the Robotics Institute of
America in 1980: ". . . a reprogrammable, multifunctional manipulator designed to
move materials, parts, tools, or specialized devices through various programmed
motions for the performance of a variety of tasks." 6 In 1988, the six-degrees-of
freedom flexible arm PUMA 560 was used to guide a needle under CT guidance into
the brain. 4 With the introduction of robotic arms came the ability to use them
as surgical assistants. In 1998, Okada et al. described a voice-controlled robot
used to hold a thoracoscope. 5 This type of robot was also used in thoracoscopic
spinal surgery. The military, having a vested interest in telepresence surgery,
helped fund the development of the da Vinci Surgical System that was approved for
use by the FDA in 2000 and designed to facilitate complex, minimally invasive
intracavitary surgeries. 7 In 2004, the FDA cleared the first commercially
available positioning device for the placement of spinal instrumentation. At
present, several systems are commercially available that utilize robotics for
spinal operations. In a recent review, Joseph et al. evaluated the current
landscape regarding safety, accuracy, and radiation exposure with the use of
these technologies. These authors concluded that "... the placement of pedicle
screws with robotics appears to be safe, and accuracy appears to be superior to
freehand placement, although the data are not conclusive." 3 There seems to be a
significant level of interest in this technology; however, only time will tell if
it will become commonplace in our field. In this issue of Neurosurgical Focus, we
visually explore the expanding role of robotics and image guidance in spinal
surgery. New robots used for the first time and existing robots used for novel
applications graphically demonstrate how our field is evolving. The days of
fearing robots are behind us as members of our specialty begin to embrace the
concept of automation. Thankfully, unlike Capek's rogue roboti, surgical robots
rising up against us and causing world destruction is unlikely!
PMID- 29963917
TI - Minimally invasive, robot-assisted iliosacral screw insertion for fusionless
fixation in children with neuromuscular scoliosis.
AB - Fusionless surgery coupled with growing rod techniques is increasingly advocated
for the treatment of early-onset scoliosis in general and neuromuscular scoliosis
in particular. Iliosacral screws have excellent biomechanical characteristics but
are hard to place safely. Here, the authors report on robot-assisted iliosacral
screw positioning as part of growing rod surgery for the fusionless correction of
early-onset scoliosis. The technique is based on a bilateral double sliding rod
construct anchored to the pelvis proximally with 6 hooks or sublaminar bands and
distally with iliosacral screws placed by the robot. The video can be found here:
https://youtu.be/5HGH_DiD-ck .
PMID- 29963918
TI - First experience with the jump-starting robotic assistance device Cirq.
AB - Since spinal navigation became applicable, including robotic assistance into
standard navigational setups seems reasonable. A newly released modular robotic
assistance for drill stabilization (Cirq, Brainlab) was used in a 74-year-old man
undergoing dynamic stabilization of L3-4 via navigated transfascial pedicle
screws. The authors demonstrate the second worldwide surgery with this device and
the second case performed in their department. They provide insight in its
applicability to estimate its further potential in spinal robotics. Although
being just the first step of this universal platform, the authors already see
clinical benefit by its ease of use and drill support. The video can be found
here: https://youtu.be/oN2ZiHFRFkU .
PMID- 29963919
TI - Parental correlates of food parenting practices: socioeconomic status, weight,
and dieting status.
AB - Little research has considered how parents' socioeconomic indicators, body mass
index (BMI), and dieting status relate to their food parenting. The current study
used self-report data from parents of young children to examine group differences
on three types of food parenting practices (Structure, Coercive Control, and
Autonomy Promotion). Few group differences were found for socioeconomic
indicators. However, parent dieting status moderated effects of parent BMI on
structure and autonomy promotion. Obese, non-dieting parents reported lower
scores on both variables. More research is needed to better understand how
parents' dieting status moderates the effects of parent's weight.
PMID- 29963920
TI - Effects of sodium glucose co-transporter 2 inhibitors on the kidney.
AB - Sodium-glucose cotransporter 2 inhibitors are antihyperglycaemic medications with
an emerging evidence base for cardiovascular and kidney disease risk reduction.
Sodium-glucose cotransporter 2 inhibitors medications lower plasma glucose by
inhibiting glucose reabsorption in the proximal tubule of the kidney independent
of insulin. Furthermore, they reduce intraglomerular pressure by restoring
tubuloglomerular feedback. Large cardiovascular outcome trials of both
empagliflozin and canagliflozin have consistently shown beneficial kidney effects
that go beyond glycaemic control, such as reducing risk for incident nephropathy
and progression of chronic kidney disease. The mechanisms by which sodium-glucose
cotransporter 2 inhibitors improve kidney outcomes are not clear. Proposed
hypotheses underpinning the kidney benefits include kidney-specific effects such
as decreased intraglomerular pressure, activation of angiotensin-(1-7) and the
Mas receptor leading to decreased inflammation, decrease in overall kidney oxygen
consumption, rise in erythropoietin levels, inhibition of the renal sodium
hydrogen exchanger and secondary kidney effects related to improvements in HbA1c
and blood pressure. This review will focus on describing the mechanisms of action
of sodium-glucose cotransporter 2 inhibitors in the kidney, clinical efficacy
data on their use in patients with chronic kidney disease, postulated physiologic
underpinnings of kidney protection observed with sodium-glucose cotransporter 2
inhibitors and the promise and potential pitfalls for their use in patients with
chronic kidney disease.
PMID- 29963921
TI - Effects of traditional balance and slackline training on physical performance and
perceived enjoyment in young soccer players.
AB - The aim of this study was to evaluate the effects of 12-week balance and
slackline training programs on physical performance and perceived enjoyment scale
in young soccer players. Forty-one preadolescent soccer players were assigned to
two experimental groups performing traditional balance (BLT) or slackline
training (SLT), and a control group. Pre-post assessment encompassed Balance
Error Scoring System (BESS), Star Excursion Balance test (SEBT), sprint with 90
degrees turns (S90), and countermovement jump (CMJ). The rate of perceived
enjoyment scale (PACES) was applied at the end of the experimental period. SLT
and BLT improved similarly in BESS, SEBT and S90. No changes were detected in the
CMJ. Regarding PACES score, SLT presented significantly higher values than BLT.
Young athletes may benefit from a motivating training approach, thus, a designed
program based on slackline drills should be preferable to improve physical
performance in terms of balance and change of direction ability in preadolescent
soccer players.
PMID- 29963922
TI - Wearable Technology Effects on Training Outcomes of Restaurant Food Handlers.
AB - Food safety training does not always result in behavior change, perhaps because
of flaws inherent in traditional training designs. New technologies such as
augmented reality headsets or head-mounted action cameras could transform the way
food safety training is conducted in the food industry. Training conducted with
wearable technology presents visual content in the first-person or actor's
perspective, as opposed to the traditional third-person or observer perspective.
This visual hands-on first-person perspective may provide an effective way of
conveying information and encouraging behavior execution because it uses the
mirror neuron system. There is little published literature about the impact of
perspective on food safety training outcomes, such as motivation. The present
study included a repeated-measures design to determine how first- and third
person camera angles affected hand washing training reactions among 108 currently
employed restaurant food handlers. Participants were assessed on their
posttraining compliance intentions, compliance self-efficacy, perceived utility
of the training, overall satisfaction with the training, and video perspective
preference. A significant proportion of food handlers (64%) preferred the first
person video perspective ( z = 5.00, P < 0.001), and a significant correlation
was found between compliance intentions and compliance self-efficacy ( r(108) =
0.361, P < 0.001) for the first-person video. No significant differences in video
preference were found for demographic variables, including age (chi2 (2, n = 104)
= 1.69, P = 0.430), which suggests that the first-person training format appeals
to a diverse workforce. These findings support the application of wearable
technology to enhance hand washing training outcomes across a wide range of
demographic groups. This research lays the framework for future studies to assess
the impact of instructional design on compliance concerning hand washing and
other food handling behaviors.
PMID- 29963923
TI - Detecting Periodicities in Eukaryotic Genomes by Ramanujan Fourier Transform.
AB - Ramanujan Fourier transform (RFT) nowadays is becoming a popular signal
processing method. RFT is used to detect periodicities in exons and introns of
eukaryotic genomes in this article. Genomic sequences of nine species were
analyzed. The highest peak in the spectrum amplitude corresponding to each exon
or intron is regarded as the significant signal. Accordingly, the periodicity
corresponding to the significant signal can be also regarded as a valuable
periodicity. Exons and introns have different periodic phenomena. The
computational results reveal that the 2-, 3-, 4-, and 6-base periodicities of
exons and introns are four kinds of important periodicities based on RFT. It is
the first time that the 2-base periodicity of introns is discovered through
signal processing method. The frequencies of the 2-base periodicity and the 3
base periodicity occurrence are polar opposite between the exons and the introns.
With regard to the cyclicality of the Ramanujan sums, which is the base function
of the transformation, RFT is suggested for studying the periodic features of
dinucleotides, trinucleotides, and q nucleotides.
PMID- 29963924
TI - Taking a Moment to Say "Thank You".
PMID- 29963927
TI - Using the Memory Validity Profile (MVP) to detect invalid performance in youth
with mild traumatic brain injury.
AB - Performance validity tests (PVT) should be used when assessing youth with mild
traumatic brain injury (MTBI). The goal of this study was to derive a new
cutscore for determining invalid performance on the Memory Validity Profile (MVP)
in youth with MTBI. Children and adolescents (N = 92; mean age =14.8 years, SD =
2.3, range =8-18) on average six months (SD = 3.6) post-MTBI were administered
the MVP as part of their assessment. Two validated PVTs [Test of Memory
Malingering (TOMM) and Medical Symptom Validity Test (MSVT)] were administered
and used to group the sample into valid (n = 73, neither TOMM/MSVT failed) and
invalid (n = 19, both TOMM/MSVT failed). New cutscores for the MVP to determine
invalid performance in this sample were established using failure on both
TOMM/MSVT as the criterion. MVP performance correlated significantly with failure
on TOMM/MSVT. Youth with invalid performance had significantly lower MVP total
scores and area under the curve was .80, suggesting good separation of groups. A
cutscore of 31 or less on the MVP provided sensitivity of 63% for detecting
invalid performance with 93% specificity. This study yields a promising new
cutscore for the MVP that has good sensitivity and strong specificity for
detecting invalid performance in youth with MTBI.
PMID- 29963928
TI - Correlation of dynamic strength in the standing calf raise with sprinting
performance in consecutive sections up to 30 meters.
AB - Sprinting represents a result-relevant task in many sports. The correlation of
sprinting performance and one-repetition maximum (1RM) in a squat has been
assumed as assured. Results of the correlation with 1RM of the plantar flexors
are still pending. Assuming an increasing relevance of the reactive working
capacity with increasing distance, a decrease of the influence of maximum
strength of the calves is conceivable. We investigated the correlation of 1RM in
a calf raise and sprint performance in consecutive sections up to 30 meters. The
results showed medium to strong, very significant correlations (p < 0.01) for
absolute (r = -0.483 to r = -0.720) and relative (r = -0.460 to -0.577) strength,
whereas an increase of the correlation throughout the course is observed. The
dynamic maximum strength of the calves is a basic prerequisite for short sprints
and should be regarded as a performance reserve.
PMID- 29963929
TI - Complete remission of agranulocytosis after splenectomy in a variant form of T
cell large granular lymphocyte leukemia.
PMID- 29963931
TI - Three dimensional kinematics of visually classified lower extremity movement
patterns during a single leg squat among people with chronic hip joint pain.
AB - OBJECTIVE: Describe the proportional occurrence of visually determined, lower
extremity movement patterns (dynamic knee valgus [DKVal], neutral [NEU], dynamic
knee varus [DKVar]) during a single leg squat (SLSquat) among patients with
chronic hip joint pain (CHJP). Compare 3D hip and pelvic kinematics among the
categories and determine whether within-session movement pattern changes are
possible among those who demonstrate DKVal or DKVar. DESIGN: Cross-sectional.
SETTING: Movement science laboratory. PARTICIPANTS: 36 patients with CHJP (18 to
40 years). MAIN OUTCOME MEASURES: Visually based classification of lower
extremity movement and 3D kinematic angles of hip and pelvis during SLSquat,
performed under usual (self-selected) and modified (therapist instruction)
conditions. RESULTS: Based on visual appraisal, 14 patients demonstrated DKVal,
22 demonstrated NEU and none demonstrated DKVar. Those with DKVal demonstrated
greater hip adduction (23.5 + 5.7o vs. 16.0 + 5.7o, p < 0.001) and internal
rotation (7.4 + 7.1o vs. 1.6 + 7.0o, p = 0.023) than those with NEU. Compared to
the usual condition, the DKVal group demonstrated significant decrease in hip
adduction (23.5 + 5.7 degrees vs. 20.9 + 5.8 degrees , p = 0.001) and internal
rotation (7.4 + 7.1 degrees vs. 5.3 + 7.8 degrees , p = .050) in the modified
condition. CONCLUSIONS: Patients with CHJP demonstrated 2 movement patterns,
DKVal and NEU. Compared to NEU, those with DKVal demonstrated greater hip
adduction and internal rotation motion and were able to make small modifications
to their movement pattern with therapist instruction.
PMID- 29963930
TI - Screening for undiagnosed atrial fibrillation.
AB - INTRODUCTION: Atrial fibrillation (AF) is a condition of global importance, and
it is associated with significant morbidity, mortality, and healthcare costs. A
considerable proportion of patients with AF are asymptomatic, and stroke may be
the first clinical manifestation of their AF diagnosis. AF screening provides an
opportunity to identify patients with undetected AF prior to suffering a
devastating complication. Areas covered: This review will provide a rationale for
AF screening; summarize AF screening methods, studies, and economic analyses;
evaluate AF as a condition meeting criteria for population screening; and discuss
potential drawbacks. Expert commentary: While AF screening is simple, low risk,
and, in most cases, low cost, additional research is needed validating new
technologies and devices; defining strategies for linking screening with
initiation of oral anticoagulation therapy and determining whether AF screening
ultimately reduces stroke and stroke-related complications and costs.
PMID- 29963932
TI - Allogeneic hematopoietic cell transplantation is potentially curative in mantle
cell lymphoma: results from a single institution study.
AB - Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative
treatment for mantle cell lymphoma (MCL). We retrospectively analyzed outcomes of
36 patients, median age of 54 (41-68) years, who underwent allo-HCT, mostly (66%)
receiving a myeloablative (MAC) regimen. Median overall survival (OS) was 86
months and 5-year OS was 54%. Median progression-free survival (PFS) was 54
months and 5-year PFS was 49%. Cumulative incidence (CI) of non-relapse mortality
(NRM) and 2-year progression were 20.1 and 22.1%, respectively. Day +100 CI of
grade II-IV acute graft-versus-host disease (GVHD) was 38.1%; 2-year CI of
moderate/severe chronic GVHD was 31.7%. Seven patients received allo-HCT as
frontline consolidation and had better OS (median = not reached versus 54 months,
p = .045). Notwithstanding the small sample size and retrospective study design,
our findings suggest a role for allo-HCT in selected MCL patients. Future
prospective studies would be needed to better define the role of allo-HCT in this
disease.
PMID- 29963933
TI - A Daily Diary Study of Drinking and Nondrinking Days in Nonstudent Alcohol Users.
AB - BACKGROUND: Emerging adults with lower educational attainment are at higher long
term risk for problematic drinking and alcohol use disorders. Efforts to gain a
more in-depth understanding of the drinking habits of nonstudent emerging adults
are critical to reduce disparities and to shed light on targets of intervention
for this vulnerable group. OBJECTIVES: The current investigation aimed to: (1)
provide a description of the daily drinking habits of nonstudent emerging adult
drinkers using a 14-day diary method, and (2) examine nondrinking days by
assessing their reasons for not drinking as well as strategies used to avoid
drinking. METHODS: Participants were 27 (55.5% women) emerging adult drinkers
recruited from the community. RESULTS: On drinking days, multilevel results
indicated that heavier alcohol use was positively associated with level of
subjective intoxication and alcohol-related problems. Men reported higher alcohol
use outcomes than women across all alcohol use indicators. Regarding
nonconsumptive days, the most frequently endorsed reasons for not drinking
largely reflected an internal motivation, while the least endorsed reasons were
related to external constraints. Pertaining to strategies used to avoid drinking,
the most frequently endorsed response related to choosing alternative enjoyable
activities. Diary compliance with the 14-day protocol was 90.9% for at least one
daily survey. Conclusion/Importance: The present investigation represents one of
the first to examine drinking behaviors using a daily diary approach with
nonstudent emerging adult drinkers. Study findings filled an important gap
regarding our understanding of the context of drinking of an at-risk and
understudied group of drinkers.
PMID- 29963934
TI - Prognostic significance of flow cytometry MRD log reduction during induction
treatment of childhood ALL.
PMID- 29963935
TI - Prognostic significance of solitary lymph node metastasis in patients with stages
IA2 to IIA cervical carcinoma.
AB - Objective To investigate the prognostic significance of and risk factors for
solitary lymph node metastasis (SLNM) of patients with cervical carcinoma.
Methods Clinical data from patients with International Federation of Gynecology
and Obstetrics (FIGO) stages IA2 to IIA cervical carcinoma who underwent radical
hysterectomy and pelvic lymphadenectomy between January 2003 and December 2010
were analysed retrospectively. Histopathological analysis was used to identify
SLNM. Long-term survival and risk factors associated with SLNM were analysed.
Results The study enrolled 302 patients with cervical cancer: 48 with SLNM (SLNM
group) and 254 patients with no lymph node metastases (nLNM group). FIGO stage,
tumour grade, depth of tumour invasion, uterine body involvement, parametrial
involvement and lymphovascular invasion differed significantly between the two
groups. Logistic regression analysis revealed that FIGO stage, depth of tumour
invasion and lymphovascular invasion were independent factors associated with
SLNM. The 5-year survival rates of the SLNM and nLNM groups were 54.2% and 87.8%,
respectively. Multivariate analysis identified SLNM as an independent factor
affecting survival. Conclusions The occurrence of just one solitary lymph node
metastasis significantly worsened the prognosis in patients with cervical
carcinoma compared with patients without lymph node metastases.
PMID- 29963936
TI - Performance of the Medical Research Council (MRC) and the Leukemia Research
Foundation (LRF) score in predicting survival benefit with hypomethylating agent
use in patients with relapsed or refractory acute myeloid leukemia.
PMID- 29963937
TI - Interaction between CYP2D6 inhibitor antidepressants and codeine: is this
relevant?
AB - INTRODUCTION: Co-occurring pain impairs depression's prognosis. Selective
serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake
inhibitors (SNRIs) are first-line pharmacotherapies for depression and inhibit
many cytochrome 2D6 enzymes. Codeine is a first-line treatment for pain and needs
to be metabolized into morphine by cytochrome 2D6 to exert its analgesic effect.
Concomitant prescription of both pharmacotherapies leads to inadequate analgesia.
Areas covered: We performed a systematic review of the literature to amalgamate
the current knowledge regarding the clinical effect of this association and
quantified its prevalence in clinical practice in the French Pays de la Loire
area using a retrospective observational cohort study design. Expert opinion: The
literature review highlighted that antidepressants with moderate-to-strong
inhibition of CYP2D6 should be avoided in patients receiving codeine. However,
0.44% of the 12,296 sampled patients received concomitant codeine and CYP2D6
inhibitor between January 2015 and June 2015. Switching drugs in both painful and
depressive patients depends on the pain and depression subtypes. Promising drugs
that both show an effect on pain and depression are currently being studied but
are not usable in clinical practice. Until then, tailored communication
reinforcement toward health-care professionals is needed to prevent these
problematic occurrences of concomitant prescription administration.
PMID- 29963938
TI - Cultural responses towards the aftermath of suicide among the Acholi in Northern
Uganda.
AB - BACKGROUND: Suicide is a public health problem in Uganda among indigenous
societies, and different societies manage its aftermath differently. AIM: To
explore how the Acholi in Northern Uganda manage the aftermath of suicide.
METHODS: We conducted a qualitative study in Gulu district, a post-conflict area
in Northern Uganda. We conducted a total of four focus group discussions (FGDs)
and 12 key informant (KI) interviews. KI interviews were conducted with community
leaders, while the FGDs were conducted with members of the general population. We
analysed the data by means of Grounded Theory. RESULTS: Our findings indicate
that rituals form a large part in managing suicide among the Acholi. Study
communities practised distancing (symbolically and physically) as a way of
dealing with the threat of suicide. CONCLUSION: Distancing was organized into two
broad themes: affect regulation and securing future generations. It is
recommended that public health interventions should utilize cultural institutions
in the prevention of suicide.
PMID- 29963939
TI - Evaluation of the Nutritional Quality of Commissary Foods Offered in American
Women's Prisons.
AB - Weight gain and obesity among female prisoners is of public health concern. This
study analyzed the nutritional quality of commissary food and recipes cooked
within eight women's prisons in the United States. Food items from commissary
lists were categorized into the MyPlate food groups. Nutrition Data System for
Research was used to analyze the nutritional content of recipes ( N = 175). Mean
nutrient content, percent Daily Values, and food group servings were calculated.
Recipes were generally high in sodium, saturated fat, added sugars, and calories
but low in vitamin D. Commissary items and recipes were both low in fruits,
vegetables, and whole grains and excessive in refined grains. Additional research
is needed to inform policies that ensure commissary offerings better reflect
dietary recommendations.
PMID- 29963940
TI - Reproductive Outcomes Among Women with Eating Disorders or Disordered Eating
Behavior: Does Methodological Approach Shape Research Findings?
AB - BACKGROUND: There is a well-documented link between eating disorders (EDs) and
adverse health outcomes, including fertility difficulties. These findings stem
largely from clinical data or samples using a clinical measure (e.g., diagnosis)
of EDs, which may limit our understanding of how EDs or disordered eating
behaviors (DEBs) shape female fertility. METHODS: We compared reproductive
outcomes from two longitudinal data sources, clinical and population-based data
from the Utah Population Database (UPDB) (N = 6,046), and nonclinical community
based data from the National Longitudinal Study of Adolescent to Young Adult
Health (Add Health) (N = 5,951). We examined age at first birth using Cox
regression and parity using negative binomial regression. RESULTS: Using the UPDB
data, women with diagnosed ED experienced later ages of first birth (hazard rate
ratio [HRR] = 0.38; p < 0.01) and lower parity (incidence rate ratio [IRR] =
0.38; p < 0.01) relative to women without EDs. Using the Add Health sample, women
who self-reported DEB experienced earlier age of first birth (HRR = 1.16; p <
0.05) and higher parity (IRR = 1.17; p < 0.01) relative to women without DEB.
CONCLUSIONS: Conflicting results suggest two sets of mechanisms,
physical/biological (sex specific) and social/behavioral (gender specific), may
be simultaneously shaping the reproductive outcomes of women with histories of
EDs or DEB. Discipline-specific methodology likely shapes Women's Health research
outcomes.
PMID- 29963941
TI - Patterns of Fertility Preservation and Pregnancy Outcome After Breast Cancer at a
Large Comprehensive Cancer Center.
AB - BACKGROUND: In the last decades, long-term outcomes of breast cancer (BC)
patients have improved, raising new survivorship issues, including fertility
preservation and safety of pregnancy after BC. This study assesses evolution in
patterns of fertility discussion/preservation over time and reports pregnancy
outcomes in a cohort of young BC patients. METHODS: A retrospective cohort of 590
BC patients aged <=40 diagnosed between 2000 and 2016 at a large cancer center
was identified. Fertility counseling and preservation patterns for patients
receiving chemotherapy were analyzed and compared for two cohorts: 2004-2006 and
2014-2016 (total n = 161). Outcomes were reported for patients with documented
pregnancy after BC. RESULTS: Significantly, more patients diagnosed in 2014-2016
had evidence of discussion on fertility issues and/or application of fertility
preservation techniques versus patients diagnosed in 2004-2006 (82.9% vs. 66.0%,
p = 0.017). In particular, there was a significant difference in rate of
documented fertility issues discussion (67.6% vs. 34.0%, p < 0.001). Age >35 and
parity were associated with lower rates of fertility discussion/preservation.
However, rates significantly improved over time (77.6% in 2014-2016 vs. 58.1% in
2004-2006 for patients aged >35, p = 0.046; 80.7% in 2014-2016 vs. 57.6% in 2004
2006 for patients with children at diagnosis, p = 0.018). Twenty-six patients
with pregnancy after BC were identified; eight delivered at the age of >40. No
complications for women or newborns were reported. Only two patients experienced
BC relapse. CONCLUSIONS: In this small retrospective cohort, no safety concerns
were identified for pregnancy after BC. The importance attributed by clinicians
to address fertility issues has increased over time.
PMID- 29963942
TI - Control of meiotic double-strand-break formation by ATM: local and global views.
AB - DNA double-strand breaks (DSBs) generated by the SPO11 protein initiate meiotic
recombination, an essential process for successful chromosome segregation during
gametogenesis. The activity of SPO11 is controlled by multiple factors and
regulatory mechanisms, such that the number of DSBs is limited and DSBs form at
distinct positions in the genome and at the right time. Loss of this control can
affect genome integrity or cause meiotic arrest by mechanisms that are not fully
understood. Here we focus on the DSB-responsive kinase ATM and its functions in
regulating meiotic DSB numbers and distribution. We review the recently
discovered roles of ATM in this context, discuss their evolutionary conservation,
and examine future research perspectives.
PMID- 29963943
TI - Reversible, functional amyloids: towards an understanding of their regulation in
yeast and humans.
AB - Protein aggregates, and in particular amyloids, are generally considered to be
inherently irreversible aberrant clumps, and are often associated with
pathologies, such as Alzheimer's disease, Parkinson's disease, or systemic
amyloidosis. However, recent evidence demonstrates that some aggregates are not
only fully reversible, but also perform essential physiological functions.
Despite these new findings, very little is known about how these functional
protein aggregates are regulated in a physiological context. Here, we take the
yeast pyruvate kinase Cdc19 as an example of a protein forming functional,
reversible, solid, amyloid-like aggregates in response to stress conditions.
Cdc19 aggregation is regulated via an aggregation-prone low complexity region
(LCR). In favorable growth conditions, this LCR is prevented from aggregating by
phosphorylation or oligomerization, while upon glucose starvation it becomes
exposed and allows aggregation. We suggest that LCR phosphorylation,
oligomerization or partner-binding may be general and widespread mechanisms
regulating LCR-mediated reversible protein aggregation. Moreover, we show that,
as predicted by computational tools, Cdc19 forms amyloid-like aggregates in
vitro. Interestingly, we also observe striking similarities between Cdc19 and its
mammalian counterpart, PKM2. Indeed, also PKM2 harbors a LCR and contains several
peptides with high amyloidogenic propensity, which coincide with known
phosphorylation sites. Thus, we speculate that the formation of reversible,
amyloid-like aggregates may be a general physiological mechanism for cells to
adapt to stress conditions, and that the underlying regulatory mechanisms may be
conserved from yeast to humans.
PMID- 29963945
TI - Evaluation of various hemostatic knot configurations performed by veterinary
students.
AB - OBJECTIVE To determine the most effective hemostatic knot configuration performed
by veterinary students following a brief training session with an experienced
surgeon and a subsequent deliberate self-training period. DESIGN Experiment.
SAMPLE 24 fourth-year veterinary students with no previous surgical knot-tying
experience. PROCEDURES In a 1-hour training session, an experienced surgeon
showed veterinary students how to perform 5 hemostatic knot configurations
(giant, slip, strangle, surgeon's, and transfixing), which they then practiced at
home on a hemostasis simulator for 2 weeks. Thereafter, students performed each
knot 4 times (twice each with monofilament and multifilament suture) on a
hemostasis simulator. An experienced surgeon evaluated the correct execution of
knots and measured their effectiveness by use of a manometer to measure vessel
pressure distal to the ligature. Each student completed a questionnaire regarding
their perceived learning and execution difficulty and sealing security for each
knot. Responses were compared among knots and suture materials. RESULTS Overall,
students considered the surgeon's knot the easiest to learn and the strangle knot
the most difficult. The slipknot was also considered the easiest knot to perform,
and the giant knot was considered the most difficult. The strangle knot was
deemed the most effective in reducing vessel pressure distal to the ligature.
CONCLUSIONS AND CLINICAL RELEVANCE The strangle knot was the most effective
hemostatic knot in inexperienced hands, although veterinary students considered
it more difficult to learn than other, perhaps more commonly taught, knots.
Therefore, teaching of the strangle knot should be encouraged in veterinary
schools.
PMID- 29963944
TI - Patterns and Correlates of Tobacco and Cannabis co-use by Tobacco Product Type:
Findings from the Virginia Youth Survey.
AB - BACKGROUND: Cannabis use is more common among tobacco users than nonusers, and co
use (i.e., use of both substances individually) may be increasing. Better
understanding of patterns and correlates of co-use is needed. The current study
aimed to compare rates and correlates of tobacco and cannabis co-use by tobacco
product among youth. METHODS: High school students who completed the 2013
Virginia Youth Survey and reported past 30-day tobacco use (cigarette, smokeless
tobacco, cigar) were included (n = 1390). Prevalence of past 30-day tobacco-only
and cannabis co-use was calculated. Demographic, tobacco, and other substance use
characteristics were compared by co-use status. Multivariate logistic regression
models examined correlates of co-use overall and by tobacco product. RESULTS:
Over half of tobacco users were co-users. Poly-tobacco use, particularly
combusted tobacco, was more prevalent among co-users. Past 30-day alcohol use and
lifetime other illegal drug use/prescription drug misuse were common correlates
of co-use. Black Non-Hispanic (NH) race/ethnicity was associated with co-use when
restricted to cigarette users. "Other" race/ethnicity was associated with co-use
in the overall model and when restricted to cigar users. Past 30-day cigarette
smoking was associated with co-use in all models except among cigar smoking co
users. Conclusions/Importance: Rates and correlates of tobacco and cannabis co
use were not uniform and differed by tobacco product type. Tobacco and cannabis
co-users may be at greater risk for negative health effects associated with
inhaled tobacco and other risky substance use. The efficacy of prevention efforts
may be improved if risk factors associated with product-specific co-use are
considered.
PMID- 29963946
TI - Ischemic necrosis of the digits and hyperlipidemia associated with
atherosclerosis in a Miniature American Shepherd.
AB - CASE DESCRIPTION A 2.5-year-old 12-kg (26.4-lb) castrated male Miniature American
Shepherd was referred because of a 3-week history of a localized crusted skin
lesion on the digital pad of digit 3 of the right hind limb. CLINICAL FINDINGS
Skin lesions were noted on the digital pads of the right hind limb. Serum
biochemical analyses indicated severe hypercholesterolemia and
hypertriglyceridemia. Ultrasonography of the terminal portion of the aorta and
other major arterial vessels revealed substantial arteriosclerotic change.
TREATMENT AND OUTCOME Medical treatments included administration of atorvastatin
calcium, a low-fat diet, and omega-3 fatty acids to reduce serum lipids
concentration; clopidogrel to prevent thrombosis; pentoxifylline to improve
microcirculatory blood flow; clomipramine hydrochloride and trazodone
hydrochloride to help with the behavioral problems; and gabapentin to help with
pain management and behavioral problems. Surgical management included amputation
of the initial digit involved, then eventually the entire initial limb involved.
The response to treatment was poor, and euthanasia was elected. Postmortem
findings revealed severe, widespread, and chronic intimal atherosclerosis; mild,
widespread, and degenerative changes in the cerebral cortex; and edema and
vascular congestion in the meninges. CLINICAL RELEVANCE To the authors'
knowledge, this was the first report of skin necrosis secondary to
atherosclerosis in a dog. Although the incidence of atherosclerosis has been
considered very low in dogs, it should be investigated in dogs with severe
hyperlipidemia. Primary hyperlipidemia has not been previously described in
Miniature American Shepherd dogs but was the suspected underlying metabolic
disorder.
PMID- 29963948
TI - What Is Your Neurologic Diagnosis?
PMID- 29963947
TI - Characterization of and factors associated with causes of pleural effusion in
cats.
AB - OBJECTIVE To characterize and investigate potential associations between causes
of pleural effusion and various clinical factors in a large cohort of affected
cats. DESIGN Retrospective case series with nested cross-sectional study. ANIMALS
380 client-owned cats with a diagnosis of pleural effusion from January 1, 2009,
through July 14, 2014, for which the cause of pleural effusion had been fully
investigated. PROCEDURES Electronic medical records were reviewed and data
collected regarding cat characteristics, clinical signs, cause of pleural
effusion, treatment, and survival status at discharge from the hospital.
Variables were examined for associations with causes of pleural effusion. RESULTS
87 (22.9%) cats died or were euthanized before discharge from the hospital.
Congestive heart failure (CHF) was the most common cause (155 [40.8%]) of pleural
effusion, followed by neoplasia (98 [25.8%]). Other causes included pyothorax,
idiopathic chylothorax, trauma, feline infectious peritonitis, and nontraumatic
diaphragmatic hernia. Cats with trauma or feline infectious peritonitis were
significantly younger than those with CHF or neoplasia. Cats with lymphoma were
significantly younger than those with carcinoma. Cats with CHF had a
significantly lower rectal temperature at hospital admission (mean +/- SD, 36.9
+/- 1.2 degrees C [98.4 +/- 2.2 degrees F]) than did cats with pleural effusion
from other causes (37.9 +/- 1.2 degrees C [100.2 +/- 2.2 degrees F]). CONCLUSIONS
AND CLINICAL RELEVANCE Cats with pleural effusion in this study had a poor
prognosis; CHF and neoplasia were common causes. Age and hypothermia may be
helpful to raise the index of suspicion for certain underlying causes of pleural
effusion in cats.
PMID- 29963949
TI - Relationship of preoperative neurologic score with intervals to regaining
micturition and ambulation following surgical treatment of thoracolumbar disk
herniation in dogs.
AB - OBJECTIVE To estimate the times required for dogs to regain micturition and
ambulation following surgical treatment for thoracolumbar Hansen type I
intervertebral disk extrusion (IVDE) and determine whether these variables were
associated with preoperative modified Frankel score (MFS). DESIGN Retrospective
case series with nested cohort study. ANIMALS 54 dogs weighing < 20 kg (44 lb)
that were surgically treated for Hansen type I IVDE at a referral hospital
between January and December 2015. PROCEDURES Medical records and CT and MRI data
were reviewed. Information was collected regarding dog signalment, type and
duration of clinical signs, preoperative MFS, degree of spinal cord compression,
type of medical and surgical treatment provided, and intervals from surgery to
regaining micturition and ambulation (outcomes). Collected data were evaluated
for correlations with outcomes. RESULTS Mean +/- SD interval from surgery to
regaining micturition was 4.1 +/- 4.4 days, and mean interval from surgery to
regaining ambulation was 13.8 +/- 25.1 days. These intervals differed
significantly. Significant negative correlations with MFS were identified for
interval to regaining micturition (r = -0.63) and interval to regaining
ambulation (r = -0.64). No other correlations with outcome were identified.
CONCLUSIONS AND CLINICAL RELEVANCE The amount of time required for dogs to regain
micturition and ambulation following surgery for thoracolumbar IVDE was
correlated with preoperative severity of clinical signs, as reflected by
preoperative MFSs. This information should be useful for pre- and postoperative
decision-making and setting of expectations for owners of and clinicians treating
affected dogs.
PMID- 29963951
TI - In This Issue * July 15, 2018.
PMID- 29963950
TI - Pathology in Practice.
PMID- 29963952
TI - Letters to the Editor.
PMID- 29963953
TI - Pathology in Practice.
PMID- 29963955
TI - Survival estimates and outcome predictors for shelter cats with feline
panleukopenia virus infection.
AB - OBJECTIVE To determine survival estimates and outcome predictors for shelter cats
with feline panleukopenia virus (FPV) infection. DESIGN Retrospective cohort
study. ANIMALS 177 shelter cats with FPV infection. PROCEDURES Medical records of
cats treated for FPV infection from 2011 through 2013 were reviewed to collect
information pertaining to signalment; history; results of physical examination,
CBC, serum biochemical analysis, and blood gas analysis; and treatments
(antimicrobials, antiparasitics, antivirals, antiemetics, analgesics, crystalloid
or colloid solutions, and blood products). Survival time and outcome predictors
were determined by means of Kaplan-Meier estimation, logistic regression, and
mixed-model ANOVA. RESULTS Median survival time after hospital admission was 3
days; 20.3% (36/177) of cats survived to discharge from the hospital. Risk of
nonsurvival was greater in cats with (vs without) signs of lethargy, rectal
temperature < 37.9 degrees C (I00.2 degrees F), or low body weight at hospital
admission. Lower (vs higher) leukocyte count on days 3,4, and 7 of
hospitalization, but not at admission, was associated with nonsurvival.
Amoxicillin-clavulanic acid, antiparasitics, and maropitant but not interferon
omega were associated with survival, whereas glucose infusion was associated with
nonsurvival. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that FPV
infection carried a poor prognosis for shelter cats. Several variables measured
at admission or during hospitalization were associated with outcome. Remarkably
and contrary to the existing literature, leukopenia at admission had no
association with outcome, possibly owing to early prevention of complications.
PMID- 29963956
TI - Effect of refrigeration of clinical canine urine samples on quantitative
bacterial culture.
AB - OBJECTIVE To examine the effect of 24 hours of refrigeration on urine samples
collected from dogs with signs of urinary tract infection (UTI). DESIGN
Prospective cross-sectional study. ANIMALS 104 dogs with signs consistent with
UTI that had a urine sample collected via cystocentesis as part of their
diagnostic workup. PROCEDURES A 1-mL aliquot of each urine sample was
refrigerated at 5 degrees C for 24 hours in a plain glass tube, then processed
for quantitative bacterial culture (QBC). A 0.5-mL aliquot was added to 3 mL of
tryptic soy broth (TSB) and refrigerated at 5 degrees C for 24 hours, then
processed for QBC. The remaining portion was immediately processed for QBC, with
results reported as numbers of bacterial colony-forming units (CFUs). Sensitivity
of the QBC for detection of bacteria (and therefore UTI) was determined for
sample refrigeration in the 2 conditions, compared with immediate processing
(reference standard). RESULTS Bacterial growth was identified in 35.6% (n = 37),
33.7% (35), and 31.7% (33) of the immediately processed, refrigerated, and
refrigerated-in-TSB urine samples, respectively. Sample refrigeration without TSB
resulted in no significant difference in CFU counts relative to immediate
processing; however, the sensitivity of this method was 95% (35/37). Sample
refrigeration with TSB resulted in significantly lower CFU counts, and
sensitivity was only 89% (33/37). CONCLUSIONS AND CLINICAL RELEVANCE Canine urine
samples collected for bacterial culture should be immediately submitted for
testing. Although CFU counts for refrigerated and immediately processed samples
were statistically similar in this study, sample refrigeration in enrichment
broth resulted in imperfect sensitivity for UTI detection and is not recommended.
PMID- 29963957
TI - Incidence and characteristics of acute-onset postoperative bacterial and sterile
endophthalmitis in dogs following elective phacoemulsification: 1,447 cases (1995
2015).
AB - OBJECTIVE To characterize and determine the incidence of acute-onset (ie,
developing <= 6 weeks after surgery) postoperative infectious and sterile
endophthalmitis in dogs following elective cataract surgery. DESIGN Retrospective
case series. ANIMALS 2,630 eyes of 1,447 dogs that underwent elective unilateral
or bilateral cataract surgery by phacoemulsification at Cornell University from
1995 through 2015. PROCEDURES Medical records were reviewed to collect and
summarize data regarding dog signalment, clinical findings, diagnostic test
results, surgery characteristics, eye or eyes affected, concurrent major systemic
diseases, treatments, and clinical outcome. RESULTS Infectious endophthalmitis
developed in 4 eyes of 4 dogs during the follow-up period, representing 0.15% of
eyes and 0.28% of dogs that underwent surgery. Unilateral sterile endophthalmitis
developed in 3 (0.11%) eyes of 3 (0.21%) dogs. All cases of infectious
endophthalmitis were unilateral and in pseudophakic eyes and followed bilateral
cataract surgeries. Clinical signs consistent with infectious endophthalmitis
developed a median of 18 days after surgery and included marked and progressive
hypopyon; Staphylococcus or Streptococcus spp were recovered from aqueous and
vitreous humor samples. All eyes with infectious endophthalmitis responded poorly
to medical treatment and were enucleated. In 2 eyes with infectious
endophthalmitis, corneal incision nonunion with epithelial downgrowth was
identified histologically and postulated as the route of bacterial entry into the
globe. CONCLUSIONS AND CLINICAL RELEVANCE Bacterial endophthalmitis following
elective phacoemulsification was uncommon in the dogs of this study. Introduction
of bacteria into the eye may occur during surgery or in the postoperative period
from corneal incisions that fail to heal normally.
PMID- 29963959
TI - What Is Your Diagnosis?
PMID- 29963958
TI - Sternotomy and ventral slot decompression for treatment of T1-2 intervertebral
disk disease in a Dachshund.
AB - CASE DESCRIPTION A 9-year-old 7.5-kg (16.5-lb) castrated male Dachshund was
referred for emergency evaluation of pelvic limb paraplegia of < 24 hours'
duration. CLINICAL FINDINGS A spinal cord lesion between T3 and L3 was suspected
given the dog's history and neurologic examination results. Computed tomography
and myelography spanning T3 through L4 identified an extradural compressive
lesion at the L3-4 disk space. Hemilaminectomy was performed, and disk material
adhered to and compressing the spinal cord was identified. However, because the
material appeared to have been present for an extended period, postoperative CT
of the cervicothoracic region was performed, which revealed extrusion of disk
material from the T1-2 space and marked spinal cord compression. TREATMENT AND
OUTCOME A sternotomy of the manubrium and ventral slot decompression of the T1-2
disk space were performed successfully without entering the thoracic cavity. A
large amount of disk material was removed from the spinal canal. No loss of
intrathoracic negative pressure was appreciated, and intraoperative complications
included only mild hemorrhage. The dog maintained pelvic limb pain sensation
postoperatively and regained motor function 2 days after surgery. CLINICAL
RELEVANCE Intervertebral disk disease is rare at T1-2 in Dachshunds. Typically, a
dorsal approach has been used to decompress the spinal cord, but findings for
this dog suggested that a ventral approach may also be appropriate. Consideration
should be given to include the T1-2 disk space when performing advanced imaging
in dogs because of the inconsistent ability to identify lesions at this location
by means of neurologic examination.
PMID- 29963960
TI - Measuring cell cycle-dependent DNA damage responses and p53 regulation on a cell
by-cell basis from image analysis.
AB - DNA damage in cells occurs from both endogenous and exogenous sources, and
failure to repair such damage is associated with the emergence of different
cancers, neurological disorders and aging. DNA damage responses (DDR) in cells
are closely associated with the cell cycle. While most of our knowledge of DDR
comes from bulk biochemistry, such methods require cells to be arrested at
specific stages for cell cycle studies, potentially altering measured responses;
nor is cell to cell variability in DDR or direct cell-level correlation of two
response metrics measured in such methods. To overcome these limitations we
developed a microscopy-based assay for determining cell cycle stages over large
cell numbers. This method can be used to study cell-cycle-dependent DDR in
cultured cells without the need for cell synchronization. Upon DNA damage
gammaH2A.X induction was correlated to nuclear enrichment of p53 on a cell-by
cell basis and in a cell cycle dependent manner. Imaging-based cell cycle staging
was combined with single molecule P53 mRNA detection and immunofluorescence for
p53 protein in the very same cells to reveal an intriguing repression of P53
transcript numbers due to reduced transcription across different stages of the
cell cycle during DNA damage. Our study hints at an unexplored mechanism for p53
regulation and underscores the importance of measuring single cell level
responses to DNA damage.
PMID- 29963962
TI - Antithrombotic therapy for venous thromboembolism in patients with cancer: expert
guidance.
AB - INTRODUCTION: Most of the current clinical guidelines recommend the use of Low
Molecular-Weight Heparins (LMWHs) for cancer-associated thrombosis (CAT). The
Hokusai VTE-cancer trial reported the first results of a direct comparison
between a direct oral anticoagulant (DOAC), edoxaban, and LMWH in this setting.
Areas covered: This review aims to critically appraise the currently available
evidence on the efficacy and safety of anticoagulant agents for the long-term
treatment of CAT and to provide an expert opinion and guidance in this field.
Expert opinion: Based on the available evidence, DOACs represent a valid
alternative to LMWH for the treatment of CAT for the majority of patients with
active cancer. Currently, most solid evidence comes from the Hokusai VTE-cancer
study, which showed that edoxaban is non-inferior to the LMWH dalteparin, with a
trend toward fewer recurrent venous thromboembolic events, but with more major
bleeding events. Similar findings were reported with rivaroxaban, although the
study was not sufficiently powered to allow definitive conclusions. The majority
of bleeding events occurred in the upper gastrointestinal tract and in patients
with gastrointestinal cancer. Thus, LMWH remains the preferred option for
patients with gastrointestinal cancer. Additional studies aimed to confirm these
findings with other DOACs are now warranted.
PMID- 29963961
TI - Tumor targeting Salmonella typhimurium A1-R in combination with gemcitabine (GEM)
regresses partially GEM-resistant pancreatic cancer patient-derived orthotopic
xenograft (PDOX) nude mouse models.
AB - Gemcitabine (GEM) is first-line therapy for pancreatic cancer but has limited
efficacy in most cases. Nanoparticle-albumin bound (nab)-paclitaxel is becoming
first-line therapy for pancreatic cancer, but also has limited efficacy for
pancreatic cancer. Our goal was to improve the treatment outcome in patient-like
models of pancreatic cancer. We previously established patient-derived orthotopic
xenografts (PDOX) pancreatic cancers from two patients. The pancreatic tumor was
implanted orthotopically in the pancreatic tail of nude mice to establish the
PDOX models. Five weeks after implantation, 50 PDOX mouse models were randomized
into five groups of 10 mice for each pancreatic cancer PDOX: untreated control;
GEM (100 mg/kg, i.p., once a week for 2 weeks); GEM + nab-PTX (GEM: 100 mg/kg,
i.p., once a week for 2 weeks, nab-PTX: 10 mg/kg, i.v., twice a week for 2
weeks); S. typhimurium A1-R (5 * 107 CFU/100 MUl, i.v., once a week for 2 weeks);
GEM + S. typhimurium A1-R (GEM: 100 mg/kg, i.p., once a week for 2 weeks, S.
typhimurium A1-R; 5 * 107 CFU/100 MUl, i.v., once a week for 2 weeks). GEM + nab
PTX was significantly more effective than GEM alone in one PDOX model (p =
0.0004), but there was no significant difference in the other PDOX model. The
combination of GEM + S. typhimurium A1-R regressed both PDOX models. These
results show S. typhimurium A1-R can overcome the ineffectiveness or partial
effectiveness of GEM in patient-like models of pancreatic cancer and demonstrate
clinical potential for this combination.
PMID- 29963963
TI - Ruminations from the Bevan Commission.
PMID- 29963965
TI - The Norwood Stage 1 procedure - conduct of perfusion: 2017 Survey results from
NPC-QIC member institutions.
AB - Hypoplastic left heart syndrome (HLHS) is a rare and severe congenital cardiac
defect. Approximately 1000 infants are born with HLHS in the United States every
year. Healthcare collaboratives over the last decade have focused on sharing
patient experiences and techniques in an effort to improve outcomes. In 2010,
cardiologists and patient families joined together to improve the care of HLHS
patients by forming the National Pediatric Cardiology Quality Improvement
Collaborative (NPC-QIC). Sixty-six of the approximately 110 institutions caring
for patients with HLHS in the United States and Canada are now members of NPC
QIC. In 2017, cardiovascular perfusionists joined the collaborative as another
specialty involved in the care of HLHS patients. Perfusionists and cardiac
surgeons developed the collaborative's first conduct of perfusion survey for the
Norwood Stage 1 procedure, specifically targeting the provision of
cardiopulmonary bypass for patients with HLHS. This manuscript discusses the
results of this survey, unveiling a significant variance in the conduct of
perfusion for this patient population.
PMID- 29963967
TI - The effects of state anxiety on analogue peritraumatic encoding and event memory:
introducing the stressful event segmentation paradigm.
AB - Cognitive theories of PTSD argue that poor recall of trauma memories results from
a stress-induced shift toward perceptual processing during encoding. The present
study assessed the extent to which self-reported state anxiety affects event
segmentation and its subsequent impact on memory performance (recall and
recognition). Event segmentation is the cognitive process of condensing
continuous streams of spatiotemporal information into discrete elements. In this
study, undergraduates without PTSD used a computer programme to segment a
stressful film and a non-stressful film and then they completed memory tasks for
each film. For the stressful film, low memory performance was associated with
high segmentation performance. A meditational analysis revealed high segmentation
performance mediated a negative relationship between state anxiety and memory
performance. Additionally, ad-hoc analyses suggest perceptual processing
primarily drives segmentation of the stressful film and conceptual processing
primarily drives segmentation of the non-stressful film.
PMID- 29963964
TI - Cellular senescence induces replication stress with almost no affect on DNA
replication timing.
AB - Organismal aging entails a gradual decline of normal physiological functions and
a major contributor to this decline is withdrawal of the cell cycle, known as
senescence. Senescence can result from telomere diminution leading to a finite
number of population doublings, known as replicative senescence (RS), or from
oncogene overexpression, as a protective mechanism against cancer. Senescence is
associated with large-scale chromatin re-organization and changes in gene
expression. Replication stress is a complex phenomenon, defined as the slowing or
stalling of replication fork progression and/or DNA synthesis, which has serious
implications for genome stability, and consequently in human diseases. Aberrant
replication fork structures activate the replication stress response leading to
the activation of dormant origins, which is thought to be a safeguard mechanism
to complete DNA replication on time. However, the relationship between
replicative stress and the changes in the spatiotemporal program of DNA
replication in senescence progression remains unclear. Here, we studied the DNA
replication program during senescence progression in proliferative and pre
senescent cells from donors of various ages by single DNA fiber combing of
replicated DNA, origin mapping by sequencing short nascent strands and genome
wide profiling of replication timing (TRT). We demonstrate that, progression into
RS leads to reduced replication fork rates and activation of dormant origins,
which are the hallmarks of replication stress. However, with the exception of a
delay in RT of the CREB5 gene in all pre-senescent cells, RT was globally
unaffected by replication stress during entry into either oncogene-induced or RS.
Consequently, we conclude that RT alterations associated with physiological and
accelerated aging, do not result from senescence progression. Our results clarify
the interplay between senescence, aging and replication programs and demonstrate
that RT is largely resistant to replication stress.
PMID- 29963966
TI - Phosphorylation of Drosophila Brahma on CDK-phosphorylation sites is important
for cell cycle regulation and differentiation.
AB - : The SWI/SNF ATP-dependent chromatin-remodeling complex is an important
evolutionarily conserved regulator of cell cycle progression. It associates with
the Retinoblastoma (pRb)/HDAC/E2F/DP transcription complex to modulate cell cycle
dependent gene expression. The key catalytic component of the SWI/SNF complex in
mammals is the ATPase subunit, Brahma (BRM) or BRG1. BRG1 was previously shown to
be phosphorylated by the G1-S phase cell cycle regulatory kinase Cyclin E/CDK2 in
vitro, which was associated with the bypass of G1 arrest conferred by BRG1
expression. However, it is unknown whether direct Cyclin E/CDK2-mediated
phosphorylation of BRM/BRG1 is important for G1-S phase cell cycle progression
and proliferation in vivo. Herein, we demonstrate for the first time the
importance of CDK-mediated phosphorylation of Brm in cell proliferation and
differentiation in vivo using the Drosophila melanogaster model organism.
Expression of a CDK-site phospho-mimic mutant of Brm, brm-ASP (all the potential
CDK sites are mutated from Ser/Thr to Asp), which acts genetically as a brm loss
of-function allele, dominantly accelerates progression into the S phase, and
bypasses a Retinoblastoma-induced developmental G1 phase arrest in the wing
epithelium. Conversely, expression of a CDK-site phospho-blocking mutation of
Brm, brm-ALA, acts genetically as a brm gain-of-function mutation, and in a Brm
complex compromised background reduces S phase cells. Expression of the brm
phospho-mutants also affected differentiation and Decapentaplegic (BMP/TGFbeta)
signaling in the wing epithelium. Altogether our results show that CDK-mediated
phosphorylation of Brm is important in G1-S phase regulation and differentiation
in vivo. ABBREVIATIONS: A-P: Anterior-Posterior; BAF: BRG1-associated factor;
BMP: Bone Morphogenetic Protein; Brg1: Brahma-Related Gene 1; Brm: Brahma; BSA:
Bovine Serum Albumin; CDK: Cyclin dependent kinase dpp: decapentaplegic; EdU: 5
Ethynyl 2'-DeoxyUridine; EGFR: Epidermal Growth Factor Receptor; en: engrailed;
GFP: Green Fluorescent Protein; GST: Glutathione-S-Transferase; HDAC: Histone
DeACetylase; JNK: c-Jun N-terminal Kinase; Mad: Mothers Against Dpp; MAPK:
Mitogen Activated Protein Kinase; MB:: Myelin Basic Protein; nub: nubbin; pH3:
phosphorylated Histone H3; PBS: Phosphate Buffered Saline; PBT: PBS Triton; PFA:
ParaFormAldehydep; Rb: Retinoblastoma protein; PCV: Posterior Cross-Vein; Snr1:
Snf5-Related 1; SWI/SNF: SWitch/Sucrose Non-Fermentable; TGFbeta: Transforming
Growth Factor beta; TUNEL: TdT-mediated dUTP Nick End Labelling; Wg: Wingless;
ZNC: Zone of Non-Proliferating Cells.
PMID- 29963968
TI - Healthy and sustainable diet and physical activity: the rationale for and
experiences from developing a combined summary score.
AB - AIMS: First, to describe the rationale for developing a combined summary score,
the Healthy and Sustainable Dietary and Physical Activity habits (HSDPA) score,
incorporating four selected dietary and physical activity aspects: (a) the New
Nordic Diet, (b) local and sustainable foods, (c) active transportation and (d)
non-exercise outdoor activities. Secondly, to describe the experiences from
constructing the HSDPA score. METHODS: Relevant literature covering the four
aspects of interest was reviewed to secure a well-grounded rationale and a theory
based approach. To measure compliance with such a broad approach targeting diet,
physical activity, health and environmental sustainability, the HSDPA score was
constructed including one subscale for each aspect. The four subscales were
constructed from questionnaire items and were equally weighted, entailing a range
from 0-10 points, hence the total HSDPA score ranged from 0-40 points. RESULTS:
In retrospect, we believe that the rationale for creating the HSDPA score is
reasonable. Still, emphasizing fewer, but the most relevant aspects, such as
reduced meat consumption and active transportation, may represent a more
functional solution than the broad approach suggested herein, both for promoting
public health and environmental sustainability, and for developing a feasible
measurement tool. CONCLUSIONS: Our experiences illustrate the importance of
methodological perspectives and scrutiny related to both the development and
testing of complex summary scores. Nevertheless, we think that combined summary
scores could be applicable for use within epidemiological studies and for
measuring the effects of interventions, if accounting for the methodological
limitations as far as possible.
PMID- 29963969
TI - Azurin interaction with the lipid raft components ganglioside GM-1 and caveolin-1
increases membrane fluidity and sensitivity to anti-cancer drugs.
AB - Membrane lipid rafts are highly ordered microdomains and essential components of
plasma membranes. In this work, we demonstrate that azurin uptake by cancer cells
is, in part, mediated by caveolin-1 and GM-1, lipid rafts' markers. This
recognition is mediated by a surface exposed hydrophobic core displayed by azurin
since the substitution of a phenylalanine residue in position 114 facing the
hydrophobic cavity by alanine impacts such interactions, debilitating the uptake
of azurin by cancer cells. Treating of cancer cells with azurin leads to a
sequence of events: alters the lipid raft exposure at plasma membranes, causes a
decrease in the plasma membrane order as examined by Laurdan two-photon imaging
and leads to a decrease in the levels of caveolin-1. Caveolae, a subset of lipid
rafts characterized by the presence of caveolin-1, are gaining increasing
recognition as mediators in tumor progression and resistance to standard
therapies. We show that azurin inhibits growth of cancer cells expressing
caveolin-1, and this inhibition is only partially observed with mutant azurin.
Finally, the simultaneous administration of azurin with anticancer therapeutic
drugs (paclitaxel and doxorubicin) results in an enhancement in their activity,
contrary to the mutated protein.
PMID- 29963971
TI - Comparison of Patient Food Intake, Satisfaction and Meal Quality Between Two Meal
Service Styles in a Geriatric Inpatient Unit.
AB - This pilot study evaluated the introduction of a bistro evening meal service in a
geriatric inpatient unit by comparing patient intake, satisfaction and meal
quality of this new service to the usual central preplated service. Ten meals
were observed under each condition (n = 30; mean age 79 years, 47% male). Data
were collected on intake of each meal component (none, 1/4, 1/2, 3/4, all;
converted to energy and protein using known food composition data), patient
satisfaction with meals (meal flavor/taste, appearance, quality, staff demeanor;
seven-point scale) and meal quality (sensory properties, temperature; five-point
scale). Independent t-tests were used to compare energy and protein intakes
between bistro and preplated services. There was no difference in mean energy or
protein intake (energy: 2524 +/- 927 kJ vs. 2692 +/- 857 kJ, p = 0.612; protein:
29 +/- 12 g vs. 27 +/- 11 g, p = 0.699) patient satisfaction or meal quality
between the bistro and preplated meal services. Patients were provided with fewer
meal items during the bistro service, but ate a higher proportion of what was
provided to them. Implementing a bistro service did not increase intake,
satisfaction or meal quality in this study, suggesting that meal plating may be
only one of many factors influencing intake and satisfaction of older inpatients.
PMID- 29963972
TI - Comparison of Stereotactic Body Radiation Therapy Combined With or Without
Transcatheter Arterial Chemoembolization for Patients With Small Hepatocellular
Carcinoma Ineligible for Resection or Ablation Therapies.
AB - INTRODUCTION: To compare the efficacy and safety of stereotactic body radiation
therapy with or without transcatheter arterial chemoembolization for patients
with small hepatocellular carcinoma who were ineligible for resection or ablation
therapies. METHODS: A total of 150 patients with 185 hepatocellular carcinoma
(<=3 nodules, Child-Turcotte-Pugh class A or B, and no vascular or extrahepatic
metastases) were treated with stereotactic body radiation therapy. In principle,
transcatheter arterial chemoembolization was combined before stereotactic body
radiation therapy (combination group), but some patients were treated with
stereotactic body radiation therapy alone. The prescribed dose of stereotactic
body radiation therapy was 48 Gy in 4 fractions at the isocenter and 40 Gy in 4
or 5 fractions at the dose covering 95% of the planning target volume. The
overall survival, progression-free survival, local progression free survival, and
complication rates were retrospectively compared between the groups. Local
progression was defined as irradiated tumor growth in dynamic computed tomography
follow-up. Tumor responses were assessed according to the Modified Response
Evaluation Criteria in Solid Tumors. Treatment-related toxicities were evaluated
according to the Common Terminology Criteria for Adverse Events version 4.0.
RESULTS: Twenty-eight and 122 patients were enrolled in the stereotactic body
radiation therapy alone and combination groups, respectively. The median follow
up periods were 16 and 29 months, respectively. The 2-year overall, progression
free, and local progression-free survival times in stereotactic body radiation
therapy alone and combination groups were 78.6% and 80.3% ( P = .6583), 49.0% and
42.9% ( P = .188), and 71.4% and 80.8% ( P = .9661), respectively. The incidence
of >=grade 3 toxicities was 17.9% in stereotactic body radiation therapy alone
group and 18.9% in combination group ( P = .903). CONCLUSIONS: Stereotactic body
radiation therapy alone may be a good treatment option for patients with small
hepatocellular carcinoma who were ineligible for resection or ablation therapies.
PMID- 29963970
TI - Aged kidney: can we protect it? Autophagy, mitochondria and mechanisms of
ischemic preconditioning.
AB - : The anti-aging strategy is one of the main challenges of the modern biomedical
science. The term "aging" covers organisms, cells, cellular organelles and their
constituents. In general term, aging system admits the existence of nonfunctional
structures which by some reasons have not been removed by a clearing system,
e.g., through autophagy/mitophagy marking and destroying unwanted cells or
mitochondria. This directly relates to the old kidney which normal functioning is
critical for the viability of the organism. One of the main problems in
biomedical studies is that in their majority, young organisms serve as a standard
with further extrapolation on the aged system. However, some protective systems,
which demonstrate their efficiency in young systems, lose their beneficial effect
in aged organisms. It is true for ischemic preconditioning of the kidney, which
is almost useless for an old kidney. The pharmacological intervention could
correct the defects of the senile system provided that the complete understanding
of all elements involved in aging will be achieved. We discuss critical elements
which determine the difference between young and old phenotypes and give
directions to prevent or cure lesions occurring in aged organs including kidney.
ABBREVIATIONS: AKI: acute kidney injury; I/R: ischemia/reperfusion; CR: caloric
restriction; ROS: reactive oxygen species; RC: respiratory chain.
PMID- 29963974
TI - A modified procedure in aortic arch replacement with no deep hypothermic
circulatory arrest.
AB - Deep hypothermia or circulation arrest is widely used during total aortic arch
replacement. However, conventional procedures have high morbidity and mortality.1
We use the "branch-first" technique2,3 combined with clamping the distal aorta,
incorporating a stented elephant trunk to avoid deep hypothermia and circulation
arrest. This technique brings us closer to the goal of arch surgery without
cerebral or visceral circulatory arrest and the morbidity of deep hypothermia.
Early results are encouraging.
PMID- 29963973
TI - Cell Line-Specific Direct Irradiation and Bystander Responses are Influenced by
Fetal Bovine Serum Serotonin Concentrations.
AB - The radiation-induced bystander effect is mechanistically complex, involving many
different signaling components. Serotonin, present in fetal bovine serum (FBS),
has been implicated in the modulation of cellular responses to radiation.
However, the role of this ubiquitous signaling molecule has yet to be elucidated
with regard to cell line-specific radiation responses. In this study, cell
survival was measured in HCT116 p53 wild-type (HCT116+/+) and HaCaT cell cultures
treated with media containing serotonin-depleted FBS and compared to our standard
FBS-supplemented media, using clonogenic assays. We utilized an enzyme-linked
immunosorbent assay to quantify the difference (4.3 +/- 1.3 ng/ml) in serotonin
concentrations among the media. Serotonin-depleted media significantly reduced
survival in both nonirradiated cell lines. Furthermore, we sought to determine
the effects to cells in this media exposed to direct irradiation as well as
bystander media from irradiated cells. Cell survival was significantly increased
when HCT116+/+ cells were directly irradiated in serotonin-depleted media, while
HaCaT cells showed no significant difference in survival between the media.
Bystander investigations demonstrated that HCT116+/+ cells were only able to
generate a bystander effect when cultured in standard media conditions containing
greater serotonin levels. Conversely, HaCaT cells were unaffected by the
different media in terms of producing a bystander response, generating bystander
effects irrespective of the media. Previous research linking serotonin receptors
to the bystander effect, together with our results, indicate that receptor
heterogeneity among cell types may underlie serotonin sensitivity in direct
irradiation and bystander responses through serotonin receptor-mediated cell
signaling cascades.
PMID- 29963975
TI - Selecting the most suitable microalgae species to treat the effluent from an
anaerobic membrane bioreactor.
AB - Conventional treatments for nutrient removal in wastewater are shifting to
Anaerobic Membrane Bioreactors, which produce a high-quality effluent with
minimum sludge production. The effluent resulting contains high nitrogen and
phosphorus load that can be eliminated by microalgae culture. The aim of this
study is to evaluate the ammonium and phosphorus removal rate of different
microalgae species in the effluent of an anaerobic treatment. For that, 4
different microalgae species have been tested (Chlamydomonas reinhardtii,
Scenedesmus obliquus, Chlorella vulgaris and Monoraphidium braunii) in batch
monoculture and mixed conditions. Results indicate that all species are able to
eliminate both P and N in the medium with high removal rates. However, a slight
interspecies competition may boost these removal rates and productivity values
ensuring, the success of the process.
PMID- 29963976
TI - Toxic politics: Acting in a permanently polluted world.
AB - Toxicity has become a ubiquitous, if uneven, condition. Toxicity can allow us to
focus on how forms of life and their constituent relations, from the scale of
cells to that of ways of life, are enabled, constrained and extinguished within
broader power systems. Toxicity both disrupts existing orders and ways of life at
some scales, while simultaneously enabling and maintaining ways of life at other
scales. The articles in this special issue on toxic politics examine power
relations and actions that have the potential for an otherwise. Yet, rather than
focus on a politics that depends on the capture of social power via publics,
charismatic images, shared epistemologies and controversy, we look to forms of
slow, intimate activism based in ethics rather than achievement. One of the goals
of this introduction and its special issue is to move concepts of toxicity away
from fetishized and evidentiary regimes premised on wayward molecules behaving
badly, so that toxicity can be understood in terms of reproductions of power and
justice. The second goal is to move politics in a diversity of directions that
can texture and expand concepts of agency and action in a permanently polluted
world.
PMID- 29963977
TI - Political airs: From monitoring to attuned sensing air pollution.
AB - In Madrid, as in many European cities, air pollution is known about and made
accountable through techno-scientific monitoring processes based on data, and the
toxicity of the air is defined through epidemiological studies and made political
through policy. In 2009, Madrid's City Council changed the location of its air
quality monitoring stations without notice, reducing the average pollution of the
city and therefore provoking a public scandal. This scandal challenged the
monitoring process, as the data that used to be the evidence of pollution could
not be relied on anymore. To identify the characteristics of some of the diverse
forms of public's participation that emerged, I route theories of environmental
sensing from STS and feminist theory through the notion of attuned sensing.
Reading environmental sensing through processes of attunement expands the ways in
which toxicity can be sensed outside of quantitative data. This mode of sensing
recognizes how the different spontaneous attunements to and with air pollution
and the scandal acknowledged Madrid's chemical infrastructure, rendering visible
qualitative conditions of toxicity. This mode of sensing politicized the toxicity
of the air not through management or policy making, nor only through established
forms environmental activism, but through contagion and accumulation of the
different forms of public participation. All together, they made air pollution a
matter of public concern. They also redistributed the actors, practices and
objects that make the toxicity not only knowable, but also accountable, and most
importantly, they opened up spaces for citizen intervention.
PMID- 29963978
TI - Hypo-interventions: Intimate activism in toxic environments.
AB - Chemical toxicity is part of everyday life in Puchuncavi. The most polluted
industrial compound in Chile, Puchuncavi is home of fourteen industrial
complexes, including the largest copper smelting plant in the country and four
thermoelectric plants. Stories of biological mutation, corrosion and death among
plants, humans, fishes and cattle are proliferate in Puchuncavi. Engaging with
the growing interest in care and affective modes of attention within STS, this
paper examines how ill, intoxicated or otherwise affected people in Puchuncavi
act upon and know about their chronic sufferings. Drawing on ethnographic
fieldwork, I focus on what I call 'hypo-interventions', or the minimal and
unspectacular yet life-enabling practices of caring, cleaning and healing the
ailments of their significant others, human and otherwise. By minutely engaging
with somatic and affective alterations in the domestic spaces of the body, the
home and the garden, Puchuncavinos render industrial harm visible and knowable,
and hence a type of political action is invoked. While outside technical
validation and alien to conventional politics, these actions have proved crucial
for people in Puchuncavi striving to persevere in the face of industrial violence
and institutional abandonment. I coin the term 'intimate activism' to describe
the ethical and political affordances of the subdued doings and engagements
deployed in Puchuncavi. Intimate activism, I claim, draws its political power on
its capacity to create minimal conditions for ethical and material endurance.
PMID- 29963979
TI - Sirt7 inhibits Sirt1-mediated activation of Suv39h1.
AB - Sirtuins regulate a variety of cellular processes through protein deacetylation.
The best-known member of mammalian sirtuin family, Sirt1, plays important roles
in the maintenance of cellular homeostasis by regulating cell metabolism,
differentiation and stress responses, among others. Sirt1 activity requires tight
regulation to meet specific cellular requirements, which is achieved at different
levels and by specific mechanisms. Recently, a regulatory loop between Sirt1 and
another sirtuin, Sirt7, was identified. Sirt7 inhibits Sirt1 autodeacetylation at
K230 and activation thereby preventing Sirt1-mediated repression of adipocyte
differentiation by inhibition of the PPARgamma gene. Here, we extend the
regulatory complexity of Sirt7-dependent restriction of Sirt1 activity by
demonstrating that Sirt7 reduces activation of a previously described prominent
Sirt1 target, the histone methyltransferase Suv39h1. We show that removal of the
acetyl-group at K230 in Sirt1 due to the absence of Sirt7 leads to
hyperactivation of Sirt1 and thereby to constantly increased activity of Suv39h1.
PMID- 29963980
TI - Darkness in the North.
PMID- 29963981
TI - A positive-feedback-based mechanism for constriction rate acceleration during
cytokinesis in Caenorhabditis elegans.
AB - To ensure timely cytokinesis, the equatorial actomyosin contractile ring
constricts at a relatively constant rate despite its progressively decreasing
size. Thus, the per-unit-length constriction rate increases as ring perimeter
decreases. To understand this acceleration, we monitored cortical surface and
ring component dynamics during the first cytokinesis of the Caenorhabditis
elegans embryo. We found that, per unit length, the amount of ring components
(myosin, anillin) and the constriction rate increase with parallel exponential
kinetics. Quantitative analysis of cortical flow indicated that the cortex within
the ring is compressed along the axis perpendicular to the ring, and the per-unit
length rate of cortical compression increases during constriction in proportion
to ring myosin. We propose that positive feedback between ring myosin and
compression-driven flow of cortex into the ring drives an exponential increase in
the per-unit-length amount of ring myosin to maintain a high ring constriction
rate and support this proposal with an analytical mathematical model.
PMID- 29963982
TI - TRPV4 is the temperature-sensitive ion channel of human sperm.
AB - Ion channels control the ability of human sperm to fertilize the egg by
triggering hyperactivated motility, which is regulated by membrane potential,
intracellular pH, and cytosolic calcium. Previous studies unraveled three
essential ion channels that regulate these parameters: (1) the Ca2+ channel
CatSper, (2) the K+ channel KSper, and (3) the H+ channel Hv1. However, the
molecular identity of the sperm Na+ conductance that mediates initial membrane
depolarization and, thus, triggers downstream signaling events is yet to be
defined. Here, we functionally characterize DSper, the Depolarizing Channel of
Sperm, as the temperature-activated channel TRPV4. It is functionally expressed
at both mRNA and protein levels, while other temperature-sensitive TRPV channels
are not functional in human sperm. DSper currents are activated by warm
temperatures and mediate cation conductance, that shares a pharmacological
profile reminiscent of TRPV4. Together, these results suggest that TRPV4
activation triggers initial membrane depolarization, facilitating both CatSper
and Hv1 gating and, consequently, sperm hyperactivation.
PMID- 29963983
TI - Control of cyclic oligoadenylate synthesis in a type III CRISPR system.
AB - The CRISPR system for prokaryotic adaptive immunity provides RNA-mediated
protection from viruses and mobile genetic elements. When viral RNA transcripts
are detected, type III systems adopt an activated state that licenses DNA
interference and synthesis of cyclic oligoadenylate (cOA). cOA activates
nucleases and transcription factors that orchestrate the antiviral response. We
demonstrate that cOA synthesis is subject to tight temporal control, commencing
on target RNA binding, and is deactivated rapidly as target RNA is cleaved and
dissociates. Mismatches in the target RNA are well tolerated and still activate
the cyclase domain, except when located close to the 3' end of the target.
Phosphorothioate modification reduces target RNA cleavage and stimulates cOA
production. The 'RNA shredding' activity originally ascribed to type III systems
may thus be a reflection of an exquisite mechanism for control of the Cas10
subunit, rather than a direct antiviral defence.
PMID- 29963984
TI - Assessing reliability in neuroimaging research through intra-class effect
decomposition (ICED).
AB - Magnetic resonance imaging has become an indispensable tool for studying
associations of structural and functional properties of the brain with behavior
in humans. However, generally recognized standards for assessing and reporting
the reliability of these techniques are still lacking. Here, we introduce a new
approach for assessing and reporting reliability, termed intra-class effect
decomposition (ICED). ICED uses structural equation modeling of data from a
repeated-measures design to decompose reliability into orthogonal sources of
measurement error that are associated with different characteristics of the
measurements, for example, session, day, or scanning site. This allows
researchers to describe the magnitude of different error components, make
inferences about error sources, and inform them in planning future studies. We
apply ICED to published measurements of myelin content and resting state
functional connectivity. These examples illustrate how longitudinal data can be
leveraged separately or conjointly with cross-sectional data to obtain more
precise estimates of reliability.
PMID- 29963985
TI - Different contributions of preparatory activity in the basal ganglia and
cerebellum for self-timing.
AB - The ability to flexibly adjust movement timing is important for everyday life.
Although the basal ganglia and cerebellum have been implicated in monitoring of
supra- and sub-second intervals, respectively, the underlying neuronal mechanism
remains unclear. Here, we show that in monkeys trained to generate a self
initiated saccade at instructed timing following a visual cue, neurons in the
caudate nucleus kept track of passage of time throughout the delay period, while
those in the cerebellar dentate nucleus were recruited only during the last part
of the delay period. Conversely, neuronal correlates of trial-by-trial variation
of self-timing emerged earlier in the cerebellum than the striatum. Local
inactivation of respective recording sites confirmed the difference in their
relative contributions to supra- and sub-second intervals. These results suggest
that the basal ganglia may measure elapsed time relative to the intended
interval, while the cerebellum might be responsible for the fine adjustment of
self-timing.
PMID- 29963986
TI - BK channel inhibition by strong extracellular acidification.
AB - Mammalian BK-type voltage- and Ca2+-dependent K+ channels are found in a wide
range of cells and intracellular organelles. Among different loci, the
composition of the extracellular microenvironment, including pH, may differ
substantially. For example, it has been reported that BK channels are expressed
in lysosomes with their extracellular side facing the strongly acidified
lysosomal lumen (pH ~4.5). Here we show that BK activation is strongly and
reversibly inhibited by extracellular H+, with its conductance-voltage
relationship shifted by more than +100 mV at pHO 4. Our results reveal that this
inhibition is mainly caused by H+ inhibition of BK voltage-sensor (VSD)
activation through three acidic residues on the extracellular side of BK VSD.
Given that these key residues (D133, D147, D153) are highly conserved among
members in the voltage-dependent cation channel superfamily, the mechanism
underlying BK inhibition by extracellular acidification might also be applicable
to other members in the family.
PMID- 29963987
TI - Bidirectional encoding of motion contrast in the mouse superior colliculus.
AB - Detection of salient objects in the visual scene is a vital aspect of an animal's
interactions with its environment. Here, we show that neurons in the mouse
superior colliculus (SC) encode visual saliency by detecting motion contrast
between stimulus center and surround. Excitatory neurons in the most superficial
lamina of the SC are contextually modulated, monotonically increasing their
response from suppression by the same-direction surround to maximal potentiation
by an oppositely-moving surround. The degree of this potentiation declines with
depth in the SC. Inhibitory neurons are suppressed by any surround at all depths.
These response modulations in both neuronal populations are much more prominent
to direction contrast than to phase, temporal frequency, or static orientation
contrast, suggesting feature-specific saliency encoding in the mouse SC.
Together, our findings provide evidence supporting locally generated feature
representations in the SC, and lay the foundations towards a mechanistic and
evolutionary understanding of their emergence.
PMID- 29963988
TI - Clinical and epidemiological aspects of microcephaly in the state of Piaui,
northeastern Brazil, 2015-2016.
AB - OBJECTIVES: To describe aspects of the microcephaly epidemic in the state of
Piaui. METHODS: All cases of congenital microcephaly confirmed in the state
between 2015 and 2016 were included (n=100). Investigation forms of the Regional
Reference Center for Microcephaly were reviewed. Discarded cases (n=63) were used
as a comparison group. RESULTS: In October, November, and December 2015 incidence
rates reached 4.46, 6.33 and 3.86/1000 live births, respectively; 44 cases were
reported in the state capital. Among the mothers of confirmed and discarded
cases, the frequency of skin rash during pregnancy was 50/97 (51.5%) and 8/51
(15.7%), respectively (p<0.001); 33 confirmed cases (35.9%) had a head
circumference z-score between -2 and -3, 23 (25%) between -3 and -4, and 8 (8.7%)
had a z-score of less than -4. Head computer tomography scans revealed
calcifications in 78/95 (82.1%) cases. Lissencephaly, hydrocephalus and agenesis
of the corpus callosum were also frequently observed. Ophthalmic findings
included retinal pigment epithelium rarefaction and atrophy. Absence of
otoacoustic emissions was observed in 21/70 cases. One newborn also presented
lower limb muscle atrophy. There were no significant differences in vaccination
rates for influenza, diphtheria-tetanus-acellular pertussis, and hepatitis B in
either group. CONCLUSIONS: The state of Piaui, like others in the northeastern
region, faced an epidemic of congenital microcephaly between 2015 and 2016,
presumably related to congenital Zika virus infection, more intense in the
capital. Current challenges include the improvement of vector control, basic
research, scaling-up of diagnostic tools for pre-natal screening of Zika virus,
vaccines, and health care for affected children.
PMID- 29963989
TI - Adiposity, inflammation and fat-soluble vitamins in adolescents.
AB - OBJECTIVE: Evaluate the association between inflammatory process, adiposity, and
vitamins A, D, and E in adolescents, according to gender. METHODS: Cross
sectional study with adolescents aged 12-19 years old of both genders attending
public schools in Recife. A questionnaire was used to collect data on
socioeconomic level, lifestyle, and food intake of adolescents. Then, an
anthropometric evaluation and a blood sampling were performed to analyze serum
concentrations of alpha-1-acid glycoprotein, retinol, beta-carotene, alpha
tocopherol, and 25-hydroxy-vitamin D. RESULTS: The levels of alpha-1-acid
glycoprotein were higher for abdominal obesity in both genders. Male adolescents
with insufficient serum alpha-tocopherol levels had low levels of alpha-1-acid
glycoprotein (p=0.03) and an increased risk of 25-hydroxy-vitamin D and beta
carotene deficiency in relation to total and abdominal fat; female adolescents
had an increased risk of insufficient beta-carotene with abdominal obesity (PR:
1.33; 95% CI: 1.2-1.5). CONCLUSION: Abdominal adiposity implies a higher risk of
inflammation and causes different changes to the levels of fat-soluble vitamins
according to gender.
PMID- 29963991
TI - Drug repositioning, a new alternative in infectious diseases.
PMID- 29963990
TI - Tailoring antimicrobials in febrile neutropenia: using faster diagnostic and
communication tools to improve treatment in the era of extensively resistant
pathogens.
PMID- 29963992
TI - Murine Double Minute-2 Links Cell Cycle Control and Inflammation in Homeostasis
and Disease.
AB - This commentary highlights the article by Fan et al that provides mechanistic
insights into murine double minute-2's anti-inflammatory role in intraocular
inflammation.
PMID- 29963994
TI - Effectiveness of vinpocetine and isosorbide-5-mononitrate on experimental
schistosomiasis mansoni: Biochemical and immunohistochemical study.
AB - Schistosomiasis is one of the most important tropical and subtropical devastating
diseases, where praziquantel is the sole drug of choice. Praziquantel effectively
kills the adult worms, however, drug resistance has been repeatedly reported.
Moreover, there is currently no efficient anti-fibrotic therapy available for
chronic schistosomiasis. So, novel drugs which exert anti-fibrotic efficacy are
urgently needed. This research is complementary to our previous work that
evaluated the anti-schistosomal effects of the anti-inflammatory vinpocetine, as
well as the vasodilator and the anti-oxidant isosorbide-5-mononitrate. In the
present study, we assessed the therapeutic efficacies of drugs in Swiss albino
female mice experimentally infected with an Egyptian strain of Schistosoma
mansoni, using some biochemical and immunohistochemical parameters. Our results
revealed that both vinpocetine and isosorbide-5-mononitrate monotherapy
significantly decreased hepatic nuclear factor-kappaB, 10 weeks post infection.
The best effects were seen in mice administered praziquantel combined with
isosorbide-5-mononitrate, as detected by reduction in hydroxyproline and collagen
contents of the liver, and significant increase in the hepatic nitric oxide
content. The data provides insight into the potential effects of the assessed
drugs with isosorbide-5-mononitrate being more superior to vinpocetine, hence it
can be used as novel adjuvant to praziquantel to alleviate schistosomal hepatic
fibrosis. However, molecular mechanism/s and clinical trials are worthy to be
scrutinized.
PMID- 29963993
TI - Conjugated Bile Acids Promote Invasive Growth of Esophageal Adenocarcinoma Cells
and Cancer Stem Cell Expansion via Sphingosine 1-Phosphate Receptor 2-Mediated
Yes-Associated Protein Activation.
AB - Esophageal adenocarcinoma (EAC) is the sixth leading cause of cancer deaths
worldwide and has been dramatically increasing in incidence over the past decade.
Gastroesophageal reflux and Barrett esophagus are well-established risk factors
for disease progression. Conjugated bile acids (CBAs), including taurocholate
(TCA), represent the major bile acids in the gastroesophageal refluxate of
advanced Barrett esophagus and EAC patients. Our previous studies suggested that
CBA-induced activation of sphingosine 1-phosphate receptor 2 (S1PR2) plays a
critical role in promoting cholangiocarcinoma cell invasive growth. However, the
role of CBAs in EAC development and underlying mechanisms remains elusive. In the
current study, we identified that the expression level of S1PR2 is correlated to
invasiveness of EAC cells. TCA significantly promoted cell proliferation,
migration, invasion, transformation, and cancer stem cell expansion in highly
invasive EAC cells (OE-33 cells), but had less effect on the lower invasive EAC
cells (OE-19 cells). Pharmacologic inhibition of S1PR2 with specific antagonist
JTE-013 or knockdown of S1PR2 expression significantly reduced TCA-induced
invasive growth of OE-33 cells, whereas overexpression of S1PR2 sensitized OE-19
cells to TCA-induced invasive growth. Furthermore, TCA-induced activation of
S1PR2 was closely associated with YAP and beta-catenin signaling pathways. In
conclusion, CBA-induced activation of the S1PR2 signaling pathway is critically
involved in invasive growth of EAC cells and represents a novel therapeutic
target for EAC.
PMID- 29963995
TI - Micron-sized domains in quasi single-component giant vesicles.
AB - Giant unilamellar vesicles (GUVs), are a convenient tool to study membrane-bound
processes using optical microscopy. An increasing number of studies highlights
the potential of these model membranes when addressing questions in membrane
biophysics and cell-biology. Among them, phase transitions and domain formation,
dynamics and stability in raft-like mixtures are probably some of the most
intensively investigated. In doing so, many research teams rely on standard
protocols for GUV preparation and handling involving the use of sugar solutions.
Here, we demonstrate that following such a standard approach can lead to the
abnormal formation of micron-sized domains in GUVs grown from only a single
phospholipid. The membrane heterogeneity is visualized by means of a small
fraction (0.1 mol%) of a fluorescent lipid dye. For
dipalmitoylphosphatidylcholine GUVs, different types of membrane heterogeneities
were detected. First, the unexpected formation of micron-sized dye-depleted
domains was observed upon cooling. These domains nucleated about 10 K above the
lipid main phase transition temperature, TM. In addition, upon further cooling of
the GUVs down to the immediate vicinity of TM, stripe-like dye-enriched
structures around the domains are detected. The micron-sized domains in quasi
single-component GUVs were observed also when using two other lipids. Whereas the
stripe structures are related to the phase transition of the lipid, the dye
excluding domains seem to be caused by traces of impurities present in the
glucose. Supplementing glucose solutions with nm-sized liposomes at millimolar
lipid concentration suppresses the formation of the micron-sized domains,
presumably by providing competitive binding of the impurities to the liposome
membrane in excess. It is likely that such traces of impurities can significantly
alter lipid phase diagrams and cause differences among reported ones.
PMID- 29963996
TI - Long-term Outcomes of Repeated Corneal Transplantations: A Prospective Dutch
Registry Study.
AB - PURPOSE: To compare long-term outcomes of repeated corneal transplantations (CT),
based on primary indication (Fuchs endothelial dystrophy [FED] vs pseudophakic
bullous keratoplasty [PBK]), surgical technique (penetrating keratoplasty [PK] vs
endothelial keratoplasty [EK]), and indication for repeated grafting. METHODS: In
this nonrandomized treatment comparison with national registry data (Netherlands
Organ Transplantation Registry, NOTR), data on all consecutive repeated CT
following primary PK or EK for FED and PBK between 1994 and 2015 were analyzed,
with a maximal follow-up of 5 years. Regraft survival was analyzed using Kaplan
Meier survival curves and univariable and multivariable Cox regression analysis.
Secondary outcomes best-corrected visual acuity, spherical equivalent, and
refractive astigmatism were compared using linear mixed-model analysis. RESULTS:
A total of 332 repeated CT were analyzed. The number of regrafts increased
significantly between 2007 and 2015 (P = .001). Overall 5-year regraft survival
was 60% and was higher for FED vs PBK (77% vs 45%, HR = 0.40, P = .001), and re
EK vs re-PK (81% vs 55%, HR = 0.51, P = .041). However, multivariable analysis
showed no significant difference in survival based on primary indication,
surgical technique, and indication for regrafting. Corrected for baseline,
secondary outcomes also did not differ between groups. CONCLUSIONS: We found a
significant increase in repeated CT, coinciding with the introduction of EK in
the Netherlands. While univariable analysis suggested better overall regraft
survival for FED and (re-)EK, multivariable analysis showed no such difference.
This may be owing to allocation of favorable cases to undergo (re-)EK. Similarly,
secondary outcomes were determined by the primary CT technique.
PMID- 29963997
TI - Primary Secretory Carcinoma of the Lacrimal Gland: Report of a New Entity.
AB - PURPOSE: Secretory carcinoma has been described in the breast, salivary glands,
skin, and other organs, but has not been reported in the lacrimal gland to date.
Since lacrimal and salivary glands show similar tumors, we hypothesized that
lacrimal secretory carcinoma may exist but has been misclassified in the past.
DESIGN: We undertook a retrospective review of all lacrimal gland tumors at 2
tertiary institutions with centralized ocular pathology practices. METHODS: A
total of 350 lacrimal tumors were reviewed by the authors. Candidate tumors were
tested for ETV-NTRK rearrangement by fluorescence in situ hybridization and the
presence of the translocation was confirmed by next-generation sequencing.
RESULTS: We identified a single case of secretory carcinoma. The diagnosis was
confirmed by demonstrating specific immunohistochemical profile and the presence
of ETV6-NTRK3 gene fusion, which is characteristic of secretory carcinoma of
other sites. The tumor occurred in a young man who was treated with surgery alone
with no recurrence during 12 years of follow-up. CONCLUSION: Secretory carcinoma
is a new lacrimal gland carcinoma type that should be added to the spectrum of
low-grade lacrimal gland tumors.
PMID- 29963999
TI - Dibutyryl cAMP- or Interleukin-6-induced astrocytic differentiation enhances
mannose binding lectin (MBL)-associated serine protease (MASP)-1/3 expression in
C6 glioma cells.
AB - Mannose-binding lectin (MBL)-Associated Serine Proteases (MASP)-1 and 3, key
enzymes in the lectin complement pathway of innate immune response, are also
expressed in glioma cell lines. We investigated MASP-1 and MASP-3 expression
during dibutyryl cyclic AMP (dbcAMP)- or Interleukin-6 (rIL-6)-induced astrocytic
differentiation of C6 glioma cells. Our results demonstrate that C6 cells express
basal levels of MASP-1 and MASP-3 and following exposure to dbcAMP or IL-6, a
consistent MASP-1 and MASP-3 mRNA up-regulation was found, with a behavior
similar to that showed by the fibrillary acidic protein (GFAP). Furthermore, in
cell conditioned media, rIL-6 stimulated MASP-3 secretion which reached levels
similar to those obtained by dbcAMP treatment. Moreover, the detection of a 46
kDa MASP-3 suggested its processing to the mature form in the extracellular cell
medium. Interestingly, the H89 PKA inhibitor, mostly affected dbcAMP-induced MASP
1 and MASP-3 mRNA levels, compared to that of rIL-6, suggesting that cAMP/PKA
pathway contributes to MASP-1 and MASP-3 up-regulation. MASP-1 and MASP-3
expression increase was concomitant with dbcAMP- or rIL-6-induced phosphorylation
of STAT3. Our findings suggest that the increase in intracellular cAMP
concentration or rIL-6 stimulation can play a role in innate immunity enhancing
MASP-1 and MASP-3 expression level in C6 glioma cells.
PMID- 29963998
TI - Therapeutic potential of dinitrobenzene sulfonic acid (DNBS)-induced colitis in
mice by targeting IL-1beta and IL-18.
AB - Interleukin (IL)-1 and IL-18 belong to the IL-1 family of ligands, and their
receptors are members of the IL-1 receptor family. Both cytokines drive an
extensive range of pro-inflammatory networks in many cell types using common
signal transduction cascades. Anyway, differences in signaling pathways exist.
With this aim in mind, we investigated by using transgenic mice the mechanisms
through the simultaneous deficiency of both IL-1beta and IL-18 could be more
protective compared to blocking the single cytokine IL-1beta or IL-18 during
colitis. Colitis was provoked in mice by instillation of dinitrobenzene sulfonic
acid (DNBS) in the colon. The results indicated that single knockout (KO) mice of
IL-1beta or IL-18, and double KO mice of both IL-1beta and IL-18 were
hyporesponsive to DNBS-induced colitis compared to wild type (WT) mice, in which
double KO were less sensitive than single KO mice. Moreover, treatment with
Anakinra (IL-1R antagonist) also ameliorated colitis, in views of macroscopic and
histological alteration, infiltration of neutrophils or Th1 cells, oxidative and
nitrosative stress. Anakinra more significantly reduced cyclooxygenase (COX-2)
and nuclear factor (NF-kappaB) levels as well as IKB-alpha degradation compared
to blocking IL-18. On the contrary, the absence of IL-18 reduced p-ERK and p-p38
mitogen-activated protein kinase (MAPKs) in a more significant way compared to
blocking IL-1beta. Thus, the double KO increased the protective effects against
colon inflammation maybe because different converging inflammatory pathways are
being inhibited. In conclusion, the blocking of both IL-1beta and IL-18 function
may be advantageous in the treatment of IBD or inflammatory diseases.
PMID- 29964001
TI - Remembering Our History.
PMID- 29964000
TI - Diagnostic and Clinical Utility of the GAD-2 for Screening Anxiety Symptoms in
Individuals With Multiple Sclerosis.
AB - OBJECTIVE: To assess the diagnostic and clinical utility of the 2-item
Generalized Anxiety Disorder Scale (GAD-2) for screening anxiety symptoms in
individuals with multiple sclerosis (MS). DESIGN: Cross-sectional. SETTING:
University-affiliated MS neurology and rehabilitation center. PARTICIPANTS: The
sample comprised adults (N=99) (ages 19-72; mean +/- SD=46.2+/-13.0; 75% women)
with a physician-confirmed MS diagnosis who were receiving care in a university
affiliated MS center. Disease durations ranged from 1 to 37 years (mean +/-
SD=10.7+/-8.4). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
Participants completed the 7-item Generalized Anxiety Disorder Scale (GAD-7) and
GAD-2. Internal consistency was calculated for both measures. Area under the
receiver operating characteristics curve (AUC), the 95% confidence interval for
the AUC, and Youden's J were calculated to determine the optimal GAD-2 cutoff
score for identifying clinically significant anxiety symptoms, as defined by the
previously validated GAD-7 cutoff score of >=8. RESULTS: Internal consistency was
excellent for the GAD-7 (Cronbach alpha=.91) and acceptable for the GAD-2
(alpha=.77), and the measures were highly correlated (r=.94). The GAD-2 had
excellent overall accuracy for identifying clinically significant anxiety
symptoms (AUC=0.97; 95% confidence interval, 0.94-1.00). A GAD-2 cutoff score of
>=3 provided an optimal balance of good sensitivity (0.87) and excellent
specificity (0.92) for detecting clinically significant anxiety symptoms.
Alternatively, a cutoff score of >=2 provided excellent sensitivity (1.00) and
fair specificity (0.76). CONCLUSIONS: The GAD-2 is a clinically useful and
psychometrically valid tool for screening anxiety symptoms in MS rehabilitation
and neurology care settings. Importantly, this tool has the potential to identify
individuals with MS who are at risk for anxiety disorders and who may benefit
from rehabilitation psychology interventions to ultimately improve functioning
and quality of life.
PMID- 29964002
TI - Dexmedetomidine as an Additive to Local Anesthesia: A Step to Development in
Dentistry.
AB - PURPOSE: The study aimed to compare the effect of dexmedetomidine added to
lidocaine against epinephrine added to lidocaine on local anesthetic potency and
to look for future prospects of dexmedetomidine as an additive to local
anesthesia in dentistry. MATERIALS AND METHODS: The study included 25 healthy
volunteers in whom extraction of all first premolars was scheduled as part of
their orthodontic treatment plan. In this split-mouth, double-blind, crossover,
randomized controlled trial, patients were randomized into 2 groups: Group 1
received injection lidocaine plus dexmedetomidine, and group 2 was administered
lidocaine plus epinephrine. Patients were assessed for the onset of action of
anesthesia, duration of analgesia, pain perception, and vital signs. RESULTS: The
mean values (+/-standard deviations) for the onset of anesthetic action in groups
1 and 2 were 113 +/- 24.9 and 141 +/- 34.8 seconds, respectively, for the
mandible. For the maxilla, the mean values were 113 +/- 24.9 seconds for group 1
and 165 +/- 43.8 seconds for group 2. The duration of anesthesia was longer in
group 1 (lidocaine plus dexmedetomidine), in which the requirement for the first
analgesic on request was seen after a longer time interval, when compared with
group 2 (lidocaine plus epinephrine). Pain perception elicited statistically
significant results with less perception of pain in group 1 (lidocaine plus
dexmedetomidine). The vital parameters remained stable, and the results were not
statistically significant. CONCLUSIONS: In this study, we observed that the
addition of dexmedetomidine to lidocaine for maxillary and mandibular nerve
blocks significantly prolonged the block duration and shortened the onset of
action, as well as improved postoperative analgesia in terms of the need for
fewer analgesics in the postoperative period. Furthermore, the vital parameters
remained stable and no complications were encountered. The findings were
supportive of the use of dexmedetomidine as an adjunct to local anesthetics in
dental procedures.
PMID- 29964003
TI - Honey protects against wings posture error and molecular changes related to
mitochondrial pathways induced by hypoxia/reoxygenation in adult Drosophila
melanogaster.
AB - We conducted an investigation to evaluate the effects of Brazilian Pampa biome
honey and its major phenolic compounds on the development of an erected wings
posture phenotype and related mitochondrial aspects induced by
Hypoxia/Reoxygenation (H/R) in Drosophila melanogaster. Flies were pre-treated
for 3 days with a 10% honey solution and different concentrations of caffeic acid
and rho-coumaric acid and then submitted to hypoxia for 3 h. We observed that
after reoxygenation, some flies acquired an erected wings posture and that this
feature may be related to mortality. In addition, H/R induced down-regulation of
ewg mRNA expression, which could be associated to the observed complex phenotype.
H/R also caused a dysregulation in opa1-like, ldh and diap genes expression and
reduced O2 fluxes in flie's mitochondria. Honey mitigated opa1-like mRNA
expression changes provoked by H/R. Differently from honey, caffeic and rho
coumaric acids displayed no protective effects. In conclusion, we report for the
first time the protective effects of honey against complex phenotypes and
mitochondrial changes induced by H/R in adult flies.
PMID- 29964004
TI - Study of rs1137101 polymorphism of leptin receptor gene with serum levels of
selenium and copper in the patients of non-ST-segment elevation myocardial
infarction (NSTEMI) in an Iranian population.
AB - OBJECTIVE: NSTEMI is a type of myocardial infarction (MI) causing partial but
progressive occlusion of cardiac coronary vessels. The aim of this study was to
investigate rs1137101 polymorphism of soluble leptin receptor (sLEPR) as well as
circulatory selenium and copper levels in NSTEMI patients and their usefulness in
analyzing susceptibility to NSTEMI. METHODS: We collected sera and whole blood of
80 NSTEMI patients and 80 healthy individuals using cTnI levels plus
electrocardiography as the "gold standard". Polymorphism analysis was done after
DNA extraction by high-resolution melt PCR, selenium and copper levels by atomic
absorption spectrophotometry, and sLEPR by ELISA. RESULTS AND DISCUTION: There
was Hardy-Weinberg (HWE) equilibrium for both patient and control loci (chi2 =
0.368434509 and 0.341447368, respectively). The frequencies of A/A, A/G, and G/G
genotypes were 18 (22%), 37 (46%), and 25 (31%) for patients, and 30 (38%), 36
(45%), and 14 (18%) for healthy controls, respectively. The frequencies of A and
G alleles were 73 (46%) and 87 (54%) for patients and 96 (60%) and 64 (40%) for
control groups. There was correlation between allele G and sLEPR level and Body
Mass Index (BMI). Selenium levels were lower in patient group than control group
(66.307 +/- 11.013 against 87.488 +/- 11.839 MUg/L; p < 0.001) but copper
concentrations were higher (1.8105 +/- 0.358 against 1.366 +/- 0.454 mg/L; p <
0.001). sLEPR levels were also higher in patient than control group (30.568 +/-
3.290 against 23.740 +/- 5.457 ng/dL; p < .001). Low selenium and high copper
concentration had positive diagnostic value for disease. CONCLUSION: We find for
the first time that there is a significant association between rs1137101
polymorphism and susceptibility to NSTEMI. There is also statistically meaningful
association between decrease in serum selenium and increase in serum copper
levels with susceptibility to NSTEMI.
PMID- 29964005
TI - Optimization and application of an HPLC method for quantification of inosine-5'
monophosphate dehydrogenase activity as a pharmacodynamic biomarker of
mycophenolic acid in Chinese renal transplant patients.
AB - BACKGROUND: The immunosuppressive agent mycophenolic acid (MPA) is a non
competitive, reversible inhibitor of inosine-5'-monophosphate dehydrogenase
(IMPDH). Thus, IMPDH activity can serve as a potential pharmacodynamic biomarker
to optimize dosing of MPA. METHODS: Peripheral blood mononuclear cells were
isolated from 2 mL blood samples and an in vitro enzymatic reaction was
subsequently performed for 120 min. To determine IMPDH activity in Chinese
healthy volunteers and renal transplant patients, a high performance liquid
chromatography assay was established and validated by subtracting adenosine
monophosphate (AMP) from blank samples for eliminating exogenous AMP
interference. RESULTS: The accuracy of our method ranged between -0.8% and 12.5%,
and the precision ranged between 0.7% and 6.3%. The mean value of IMPDH activity
across 11 healthy volunteers was 46.60 +/- 14.28 MUmol/s/mol AMP. A negative
relationship between MPA concentration and IMPDH activity was observed in four
renal transplant patients treated with MPA 13 days post-transplantation, while
the inhibitory rate of IMPDH activity ranged from 24% to 42%. CONCLUSION: A
bioanalytical assay for IMPDH quantification was optimized and evaluated. The
differences in the pharmacodynamics of MPA between Asians and Caucasians may
provide some evidence for dosing differences among ethnicities.
PMID- 29964006
TI - Reproductive hormones modulate differentially brain and ovarian vasotocin
receptor gene expression in early and late recrudescent catfish, Heteropneustes
fossilis.
AB - Investigations on the role of the reproductive hormones on VT receptor gene
expression are lacking in teleosts. Previously we reported that gonadotropin and
steroid hormones modulate the secretion and gene expression of brain and ovarian
vasotocin (VT) in the catfish Heteropneustes fossilis. In continuation, in the
present study we investigated the role of estradiol-17beta (E2), the maturation
inducing steroid (MIS) 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17,20beta-DP),
and human chorionic gonadotropin (hCG) on the expression of VT receptor genes
(v1a1, v1a2 and v2a) in the brain and ovary of the catfish in early
(previtellogenic, preparatory) and late (post vitellogenic, prespawning) phases
of the ovarian cycle. The steroid treatments (in vivo and in vitro) modulated
only the v1a1 and v1a2 expression in both tissues, but not the v2a expression.
The E2-induced modulation of the v1a1 and v1a2 gene expression varied with the
reproductive phase. In the preparatory phase, E2 up regulated the expression of
brain and ovarian v1a1 and v1a2 gene expression, the response varied with the
dose and duration. In the prespawning phase, E2 inhibited the expression in a
dose- and duration-dependent manner. On the other hand, 17,20beta-DP up regulated
the expression of brain and ovarian v1a1 and v1a2 in both phases, and the
response was higher in the prespawning phase and varied with dose and duration.
In contrast to the steroid effects, the hCG treatment modulated the expression of
all the VT receptor genes only in the prespawning phase and the response varied
with dose and duration. The results indicate differential modulatory roles of
steroid hormones and hCG on the VT receptor gene expression, to mediate VT's
reproductive or osmoregulatory functions. While the hCG effect on v1a type
receptor expression may be steroid- dependent, that of v2a expression seems to be
steroid-independent.
PMID- 29964007
TI - Is the membrane estrogen receptor, GPER1, a promiscuous receptor that modulates
nuclear estrogen receptor-mediated functions in the brain?
AB - Contribution to Special Issue on Fast effects of steroids. Estrogen signals both
slowly to regulate transcription and rapidly to activate kinases and regulate
calcium levels. Both rapid, non-genomic signaling as well as genomic
transcriptional signaling via intracellular estrogen receptors (ER)s can change
behavior. Rapid non-genomic signaling is initiated from the plasma membrane by a
G-protein coupled receptor called GPER1 that binds 17beta-estradiol. GPER1 or
GPR30 is one of the candidates for a membrane ER (mER) that is not only highly
expressed in pathology i.e. cancers but also in several behaviorally-relevant
brain regions. In the brain, GPER1 signaling, in response to estrogen,
facilitates neuroprotection, social behaviors and cognition. In this review, we
describe several notable characteristics of GPER1 such as the ability of several
endogenous steroids as well as artificially synthesized molecules to bind the
GPER1. In addition, GPER1 is localized to the plasma membrane in breast cancer
cell lines but may be present in the endoplasmic reticulum or the Golgi apparatus
in the hippocampus. Unusually, GPER1 can also translocate to the perinuclear
space from the plasma membrane. We explore the idea that subcellular localization
and ligand promiscuity may determine the varied downstream signaling cascades of
the activated GPER1. Lastly, we suggest that GPER1 can act as a modulator of
ERalpha-mediated action on a convergent target, spinogenesis, in neurons that in
turn drives female social behaviors such as lordosis and social learning.
PMID- 29964008
TI - Knockdown of ADAM17 inhibits cell proliferation and increases oxaliplatin
sensitivity in HCT-8 colorectal cancer through EGFR-PI3K-AKT activation.
AB - We investigated the role of a disintegrin and metalloproteinase 17 (ADAM17) in
chemo resistance, and to clarify the mechanism underlying reverse of L-OHP
resistance by knockdown of ADAM17. CRC tissues with corresponding adjacent normal
tissues were collected. The mRNA and protein expression of ADAM17 in tissues were
detected by RT-qPCR, immunohistochemistry and Western blot. The prognostic impact
of ADAM17 expression were then validated in TCGA database to confirm the results.
Resistance to oxaliplatin was induced in HCT-8 (HCT-8/L-OHP) colorectal cancer
cell line by exposing cell to increasing concentrations of L-OHP. MTT were used
to evaluate the resistance to L-OHP. Subsequently, Knockdown of ADAM17 in HCT-8
and HCT-8/L-OHP cells to explore the mechanism through which ADAM17 shRNA
reverses L-OHP resistance. Our result showed that ADAM17 was higher expression in
the cancerous tissue and related to the chemosensitivity. Moreover, ADAM17 shRNA,
AG1478 and LY294002 could inhibit cell proliferation, induce apoptosis and
increase oxaliplatin sensitivity in HCT-8/L-OHP and parental colorectal cancer
cell line, but nonsense shRNA did not show this effect. Western blot analysis
further confirmed that EGFR/PI3K/AKT signaling pathway is involved in ADAM17
shRNA inhibiting proliferation and chemosensitivity of HCT-8/L-OHP and HCT-8
cells. The present study provides the evidence that downregulation of ADAM17
could increase the sensitivity to chemotherapy, inhibit cell proliferation,
induce apoptosis, and reverse oxaliplatin resistance via suppression of the
EGFR/PI3K/AKT signaling pathway in CRC.
PMID- 29964009
TI - Natronomonas pharaonis halorhodopsin Ser81 plays a role in maintaining chloride
ions near the Schiff base.
AB - Optogenetic technologies have often been used as tools for neuronal activation or
silencing by light. Natronomonas pharaonis halorhodopsin (NpHR) is a light-driven
chloride ion pump. Upon light absorption, a chloride ion passes through the cell
membrane, which is accompanied by the temporary binding of a chloride ion with
Thr126 at binding site-1 (BS1) near the protonated Schiff base in NpHR. However,
the mechanism of stabilization of the binding state between a chloride ion and
BS1 has not been investigated. Therefore, to identify a key component of the
chloride ion transport pathway as well as to acquire dynamic information about
the chloride ion-BS1 binding state, we performed a rough analysis of the chloride
ion pathway shape followed by molecular dynamics (MD) simulations for both wild
type and mutant NpHR structures. The MD simulations showed that the hydrogen bond
between Thr126 and the chloride ion was retained in the wild-type protein, while
the chloride ion could not be retained at and tended to leave BS1 in the S81A
mutant. We found that the direction of the Thr126 side chain was fixed by a
hydroxyl group of Ser81 through a hydrogen bond and that Thr126 bound to a
chloride ion in the wild-type protein, while this interaction was lost in the
S81A mutant, resulting in rotation of the Thr126 side chain and reduction in the
interaction between Thr126 and a chloride ion. To confirm the role of S81, patch
clamp recordings were performed using cells expressing NpHR S81A mutant protein.
Considered together with the results that the NpHR S81A-expressing cells did not
undergo hyperpolarization under light stimulation, our results indicate that
Ser81 plays a key role in chloride migration. Our findings might be relevant to
ongoing clinical trials using optogenetic gene therapy in blind patients.
PMID- 29964010
TI - Downregulation of RASSF6 promotes breast cancer growth and chemoresistance
through regulation of Hippo signaling.
AB - This study aims to investigate the clinical significance and biological function
of RASSF6 in human breast cancers. RASSF6 protein was found to be downregulated
in 42 of 95 human breast cancer tissues by immunohistochemistry, which was
associated with advanced TNM stage and nodal metastasis. The rate of RASSF6
downregulation was higher in Triple-negative breast cancer (TNBC). Downregulation
of RASSF6 protein was also found in breast cancer cell lines, especially in TNBC
cell lines. Overexpression RASSF6 inhibited cell growth rate and colony formation
ability in MDA-MB-231 cell line. Depletion of RASSF6 promoted proliferation rate
and colony formation ability in T47D cell line. Flow cytometry/PI staining
demonstrated that RASSF6 inhibited cell cycle transition. AnnxinV/PI analysis
showed that RASSF6 overexpression upregulated apoptosis induced by cisplatin
(CDDP) while RASSF6 depletion inhibited apoptosis. JC-1 staining showed that
RASSF6 overexpression inhibited mitochondrial membrane potential. Western blot
analysis demonstrated that RASSF6 repressed cyclin D1, YAP while upregulated p21,
cleaved caspase 3 and cytochrome c expression. In addition, RASSF6 activated
Hippo signaling pathway by upregulating MST1/2 and LATS1 phosphorylation.
Restoration of YAP inhibited cleaved caspase 3 and cytochrome c which were
induced by RASSF6. Restoration of YAP also reduced the rate of CDDP induced
apoptosis. In conclusion, this study provided evidence that RASSF6 functions as a
potential tumor suppressor in human breast cancer through activation of Hippo
pathway.
PMID- 29964011
TI - UCH-L1 inhibition aggravates mossy fiber sprouting in the pentylenetetrazole
kindling model.
AB - Mossy fiber sprouting (MFS) is a pathological phenomenon that is commonly
observed in epilepsy, and plentiful data reveal that abnormal phosphorylated
modification of tau protein plays a critical role in MSF by the regulation of
microtubule dynamics and axonal transport. Ubiquitin C-terminal hydrolase L1 (UCH
L1), a proteasomal deubiquitinating enzyme, has been proved to be associated with
tau aggregation through mediating degradation of ubiquitinated and
hyperphosphorylated tau. Thus, this study aimed to determine the expression of
UCH-L1 in the rat hippocampus during the pentylenetetrazole (PTZ)-induced process
and to demonstrate the possible correlation with MFS in epileptogenesis. Seizures
were established by intraperitoneal injection of PTZ and LDN-57444 was used to
inhibit the hydrolase activity of UCH-L1. We used western blot,
immunofluorescence, immunoprecipitation, and timm staining to detect
phosphorylated modification of tau and MSF. The results presented that LDN-57444
induced the deteriorated severity of seizures, increased phosphorylation of tau
and increased distribution of Timm granules in both the supragranular region of
the dentate gyrus (DG) and the stratum pyramidale of CA3 subfield. Our results
suggest that UCH-L1 may be associated with hippocampal MSF followed the
epileptogenesis through mediating phosphorylation of tau. UCH-L1 may be a
potential and novel therapeutic target to limit epileptogenesis.
PMID- 29964012
TI - Transactivation of PTGS2 by PAX5 signaling potentiates cisplatin resistance in
muscle-invasive bladder cancer cells.
AB - Cisplatin (CDDP)-based systematic chemotherapy remains the mainstay of treatment
for muscle-invasive bladder cancer (MIBC). However, acquired resistance to CDDP,
a multifactorial process governed by an array of signals acting at different
levels, is the major problem in BC treatment. Here, we report for the first time
that, expression of Paired-box gene 5 (PAX5), a B-cell essential transcription
factor, was significantly induced in CDDP-resistant BC tissues and in
experimentally-induced CDDP-resistant BC cells. Inhibition of PAX5 expression by
shRNA treatment effectively improved CDDP sensitivity in BC cells, whereas
overexpression of PAX5 potentiated CDDP resistance through supporting BC cell
survival. Mechanistically, using luciferase reporter and chromatin
immunoprecipitation assays, we identified prostaglandin-endoperoxide synthase 2
(PTGS2, also called COX2), a potent enzyme responsible for prostanoids formation
and inflammatory response, as the direct down-stream target of PAX5. PAX5 exerted
its oncogenic function during the pathogenesis of CDDP resistance via stimulation
of PTGS2 transcription. These observations collectively suggest that
dysregulation of PAX5/PTGS2 cascade plays a causal role in the induction of CDDP
resistance and gene silencing approaches targeting this pathway may therefore
provide a novel therapeutic strategy for overcoming CDDP resistance in BC.
PMID- 29964013
TI - TMEM16F/ANO6, a Ca2+-activated anion channel, is negatively regulated by the
actin cytoskeleton and intracellular MgATP.
AB - Anoctamin 6 (ANO6/TMEM16F) is a recently identified membrane protein that has
both phospholipid scramblase activity and anion channel function activated by
relatively high [Ca2+]i. In addition to the low sensitivity to Ca2+, the
activation of ANO6 Cl- conductance is very slow (>3-5 min to reach peak level at
10 MUM [Ca2+]i), with subsequent inactivation. In a whole-cell patch clamp
recording of ANO6 current (IANO6,w-c), disruption of the actin cytoskeleton with
cytochalasin-D (cytoD) significantly accelerated the activation kinetics, while
actin filament-stabilizing agents (phalloidin and jasplakinolide) commonly
inhibited IANO6,w-c. Inside-out patch clamp recording of ANO6 (IANO6,i-o) showed
immediate activation by raising [Ca2+]i. We also found that intracellular ATP (3
mM MgATP in pipette solution) decelerated the activation of IANO6,w-c, and also
prevented the inactivation of IANO6,w-c. However, the addition of cytoD still
accelerated both activation and inactivation of IANO6,w-c. We conclude that the
actin cytoskeleton and intracellular ATP play major roles in the Ca2+-dependent
activation and inactivation of IANO6,w-c, respectively.
PMID- 29964014
TI - Enzymatic characterization and crystal structure of biosynthetic alanine racemase
from Pseudomonas aeruginosa PAO1.
AB - Alanine racemase is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that
reversibly catalyzes the conversion of l-alanine to d-alanine. d-alanine is an
essential constituent in many prokaryotic cell structures. Inhibition of alanine
racemase is lethal to prokaryotes, creating an attractive target for designing
antibacterial drugs. Here we report the crystal structure of biosynthetic alanine
racemase (Alr) from a pathogenic bacteria Pseudomonas aeruginosa PAO1. Structural
studies showed that P. aeruginosa Alr (PaAlr) adopts a conserved homodimer
structure. A guest substrate d-lysine was observed in the active site and refined
to dual-conformation. Two buffer ions, malonate and acetate, were bound in the
proximity to d-lysine. Biochemical characterization revealed the optimal reaction
conditions for PaAlr.
PMID- 29964015
TI - Polymorphisms of ABCG2 and its impact on clinical relevance.
AB - Human ABCG2 is one of the most important ATP-binding cassette (ABC) transporters.
This protein functions as a xenobiotic transporter of large, hydrophobic,
positively or negatively charged molecules, a wide variety anticancer drugs,
fluorescent dyes, and different toxic compounds found in normal food. SNPs in
ABCG2 may affect absorption and distribution of these substrates, altering the
accumulation, effectiveness and toxicity of compounds or drugs in large
populations. Its transport properties have been implicated clinically and ABCG2
expression is linked with different disease states. We reviewed the SNPs of ABCG2
in clinical relevance about gout, acute myeloid leukemia, solid tumors, and other
diseases.
PMID- 29964016
TI - Tas2r125 functions as the main receptor for detecting bitterness of tea catechins
in the oral cavity of mice.
AB - We attempted to identify mouse bitter taste receptors, Tas2rs, that respond to
tea catechins. Among representative tea catechins, avoidance behavior of mice to
(-)-epicatechin gallate (ECg) was the strongest, followed by (-)-epigallocatechin
gallate (EGCg). Therefore, we measured ECg response using Tas2rs-expressing
cells. Among the 35 members of Tas2r family, Tas2r108, 110, 113, 125, and 144
responded to ECg. Among these receptors, Tas2r113 and 125 also responded to EGCg.
Because the response profiles of Tas2r125 were consistent with the results of the
behavior assays, it was considered that Tas2r125 functions as the main receptor
for detecting bitterness of tea catechins in the oral cavity. To determine the
involvement of Tas2rs in the physiological action of catechins, mRNA expression
of 5 Tas2rs was investigated in various tissues. Because mRNA expression of
Tas2r108 was observed in some tissues including the gastrointestinal tract, it
may be envisaged that Tas2r108 plays a part in exerting the physiological action
of ECg. Tas2r125 expression was not observed in any of the tested tissues except
the circumvallate papillae. Therefore, Tas2r125 was considered to mainly function
in the events of catechin reception in the oral cavity.
PMID- 29964017
TI - Overexpression of FGF19 alleviates hypoxia/reoxygenation-induced injury of
cardiomyocytes by regulating GSK-3beta/Nrf2/ARE signaling.
AB - Fibroblast growth factor 19 (FGF19) has emerged as a crucial cytoprotective
regulator that antagonizes cell apoptosis and oxidative stress under adverse
conditions. However, whether FGF19 plays a cytoprotective role in preventing
myocardial damage during myocardial ischemia/reperfusion injury remains unknown.
In this study, we aimed to investigate the potential role of FGF19 in regulating
hypoxia/reoxygenation (H/R)-induced injury of cardiomyocytes in vitro. We found
that FGF19 expression was upregulated in response to H/R treatment in
cardiomyocytes. Silencing of FGF19 significantly inhibited viability and
increased apoptosis and reactive oxygen species (ROS) generation in
cardiomyocytes with H/R treatment. In contrast, overexpression of FGF19 improved
viability and inhibited apoptosis and ROS generation induced by H/R treatment,
showing a cardioprotective effect. Moreover, we found that FGF19 regulated the
phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) and the nuclear
translocation of nuclear factor-E2-related factor 2 (Nrf2). In addition, FGF19
promoted the activation of Nrf2-mediated antioxidant response element (ARE)
antioxidant signaling. Notably, treatment with a GSK-3beta inhibitor
significantly abrogated the adverse effects of FGF19 silencing on H/R-induced
injury, whereas silencing of Nrf2 partially blocked the FGF19-mediated
cardioprotective effect against H/R-induced injury in cardiomyocytes. Taken
together, our findings demonstrate that FGF19 alleviates H/R-induced apoptosis
and oxidative stress in cardiomyocytes by inhibiting GSK-3beta activity and
promoting the activation of Nrf2/ARE signaling, providing a potential therapeutic
target for prevention of myocardial injury.
PMID- 29964019
TI - Invited Commentary.
PMID- 29964018
TI - Immunoprotective responses against murine sarcocystosis by beta - Irradiated
sporocysts.
AB - This study aimed to induce protective immunity against infection with Sarcocystis
muris in experimental mice using beta-irradiated sporocysts. Mice were vaccinated
with 50 sporocysts of S. muris which were exposed to 1.84 MUSv beta-irradiation
for 2, 4 and 8 h. After challenge infection, different samples were taken for
evaluation. Serum and intestinal wash were assayed for IFN-gamma and IgA,
respectively. Mesenteric lymph nodes (MLNs) and spleen were investigated for CD4+
and CD8+ T cells using immunohistochemistry. For liver, the morphological changes
in parasitic stages and the count of infiltrated CD8+ T, NK1.1+ and FasL+ cells
were also investigated. Real time (RT) - PCR was used for detection of liver MHC
I, CD1d, IFN-gamma, perforin and FasL as well as the parasite 18S ribosomal(r)
RNA in liver and muscle tissues. Alterations of liver parasitic stages as well as
a decrease in the infection with the parasite in both of liver and muscle tissues
were dependent on radiation exposure time. An investigation for the mechanism of
immunoprotection showed an increase in liver NK1.1+ & FasL+ cells, serum IFN
gamma and intestinal IgA, while CD4+ and CD8+ T showed a remarkable increase in
MLNs and spleen. FasL expression increased in the liver dependently on radiation
exposure time, while perforin, MHC I and CD1d were not. beta-irradiated
sporocysts with 1.84 MUSv for 8 h s could induce the highest protection against
infection with Sarcocystis. This could be largely relied on the increased
infiltration of NK cells and associated higher expression of FasL in the liver.
PMID- 29964020
TI - Invited Commentary.
PMID- 29964021
TI - Impact of a Composite Valved RV-PA Graft After Stage 1 Palliation.
AB - BACKGROUND: The use of a valved right ventricular to pulmonary artery shunt
(RVPAS) has been reported by some to improve pulmonary artery growth after stage
1 palliation (S1P). METHODS: We retrospectively reviewed all patients undergoing
an S1P with an RVPAS between January 2013 and May 2017, stratified by RVPAS type:
a ring-reinforced polytetrafluoroethylene (PTFE) graft or a composite graft that
included a distal valved femoral or saphenous vein homograft. We examined the
association of RVPAS type on postoperative hemodynamics, time to reintervention,
pulmonary artery growth, and survival. RESULTS: Among 94 infants, 56 (60%)
underwent PTFE-only shunt, 24 (25%) underwent femoral vein homograft, and 14
(15%) underwent saphenous vein homograft, and no relevant risk factor differences
were found between the groups. Arterial saturation was 2.3% higher (p = 0.014)
and serum lactic acid was 1.24 mg/dL lower (p = 0.03) in the femoral vein
homograft group than in the PTFE-only group, although venous saturation was
similar. By 60 days, 50% of patients with saphenous vein homograft had a
reintervention compared with 5% with PTFE graft (p < 0.0001) and 12% with femoral
vein homograft (p = 0.2 versus PTFE). At the time of stage 2 palliation, no
differences were found in pulmonary artery size or growth over time by either
echocardiogram or angiography or in the density of aortopulmonary collaterals or
degree of tricuspid regurgitation. The 12-month survival was similar between the
groups. CONCLUSIONS: The use of an interposition femoral vein homograft into the
RVPAS may enhance perioperative stability, but it does not substantially improve
interstage growth of the pulmonary arteries. Use of saphenous vein homograft is
associated with earlier time to reintervention after S1P.
PMID- 29964022
TI - Effect of Aneurysm and Bicuspid Aortic Valve on Layer-Specific Ascending Aorta
Mechanics.
AB - BACKGROUND: Previous studies have not examined the participation of intimal,
medial, and adventitial layers in providing mechanical strength to the ascending
thoracic aortic aneurysm (ATAA) wall compared with the nonaneurysmal aorta. In
this study we compared the mechanical properties of intact wall and its layers
among ATAAs and nonaneurysmal aortas, with explicit consideration of the effects
of valve morphology; that is, bicuspid aortic valve (BAV) versus tricuspid aortic
valve (TAV), and aortic quadrant. METHODS: Whole ATAAs were taken from patients
undergoing elective repair and nonaneurysmal aortas from age-matched autopsy
subjects. These were cut into 2 circumferential and longitudinal tissue strips
for the intact wall and its layers per quadrant, permitting examination of the
aortic wall as a multilayered structure. Tissue underwent tensile testing for
determination of failure properties. RESULTS: Intact wall and layer-specific
failure stretches (ie, extensibilities) were significantly greater in
nonaneurysmal and BAV-ATAA than in TAV-ATAA, unaccounted for by elastin/collagen
content changes. Intact wall failure stress (ie, strength) was significantly
greater in BAV-ATAA than in TAV-ATAA, in analogy with medial failure stress.
Failure stress and stretch associated negatively with age in most subject groups,
layers, and intact wall, but failure stretch correlated positively with residual
stretch (ie, structural bonds between layers). CONCLUSIONS: No mechanical
vulnerability of BAV-ATAA was found, corroborating current conservative
guidelines regarding the management of bicuspid aortopathy. Weakening and added
vulnerability was found in patients with valvular deficiency, aortic root
aneurysm, hypertension, and hyperlipidemia. Aging led to increased susceptibility
to dissection initiation or full rupture, or both, in both patient classes.
PMID- 29964023
TI - Failure to reactivate salient episodic information during indirect and direct
tests of memory retrieval.
AB - Several fMRI and EEG studies have demonstrated that successful episodic retrieval
is accompanied by the reactivation of cortical regions that were active during
encoding. These findings are consistent with influential models of episodic
memory that posit that conscious retrieval (recollection) relies on hippocampally
mediated cortical reinstatement. Evidence of reactivation corresponding to
episodic information that is beyond conscious awareness at the time of memory
retrieval, however, is limited. A recent exception is from an EEG study by
Wimber, Maabeta, Staudigl, Richardson-Klavehn, and Hanslmayr et al. (2009) in
which words were encoded in the context of highly salient visual flicker
entrainment and then presented at retrieval in the absence of any flicker. In
that study, coherent (phase-locked) neural activity was observed at the
corresponding entrained frequencies during retrieval, consistent with the notion
that encoding representations were reactivated. Given the important implications
of unconscious reactivation to past findings and the modeling literature, the
current study set out to provide a direct replication of the previous study.
Additionally, an attempt was made to extend such findings to intentional
retrieval by acquiring EEG while subjects were explicitly asked to make memory
judgments about the flicker frequency from encoding. Throughout a comprehensive
set of analyses, the current study consistently failed to demonstrate evidence
for unconscious reactivation, and instead provided support that test items were
indistinguishable according to their prior encoding context. The findings thus
establish an important boundary condition for the involvement of cortical
reinstatement in episodic memory.
PMID- 29964024
TI - Late-emerging effects of perinatal undernutrition in neuronal limbic structures
underlying the maternal response in the rat.
AB - Maternal care in the rat is an ancient behavioral response to specific
multisensory inputs widely integrated in a complex forebrain, limbic and brain
stem network to meet the basic needs of the young. Early undernutrition
interferes with the morphofunctional organization of the brain, including
maternal circuitry. The late-emerging effects of pre- and neonatal undernutrition
on nest building and pup retrieval by lactating Wistar rats were correlated with
dendritic arbor and perikaryon measurements (Golgi-Cox) in layer II pyramidal
neurons of the anterior cingulate cortex, layer III pyramidal neurons of the
medial prefrontal cortex and multipolar basolateral amygdala neurons examined on
lactation days 4 and 12. In the underfed group, pregnant F0 dams received
different percentages of a balanced diet. After birth, prenatally underfed (F1)
pups continued the undernutrition by remaining with a nipple-ligated mother for
12 h. Weaning occurred at 25 days of age, and pups were subsequently provided an
ad libitum diet. At 90 days of age, F1 dams were maternally tested. Early
underfed dams showed significant reductions in nest building and prolonged
retrieval latencies for grasping pups by inappropriate body areas. The behavioral
alterations were concurrent with highly significant reductions in the somatic
cross-sectional area and perimeter, spine density and dendritic crossings of
cingulate cells and medial prefrontal cortical pyramids, as well as smaller
effects on amygdala neurons. The anatomical findings suggest different
postsynaptic organizations that may affect the neuronal excitability stages for
the integration and encoding of cues triggering the altered maternal response
components of early underfed dams.
PMID- 29964025
TI - Neonatal bladder inflammation alters the role of the central amygdala in
hypersensitivity produced by Acute Footshock stress in adult female rats.
AB - There is increasing evidence that chronic pain may be associated with events that
occur during critical periods of development. Recent studies have identified
behavioral, spinal neurophysiological and spinal/peripheral neurochemical
differences in rats that have experienced neonatal bladder inflammation (NBI): a
putative model of the chronically painful bladder disorder, interstitial
cystitis. Stress has been shown to exacerbate symptoms of interstitial cystitis
and produces bladder hypersensitivity in animal models. We recently reported that
Acute Footshock-induced bladder hypersensitivity was eliminated in otherwise
normal rats by prior bilateral lesions of the central nucleus of the amygdala.
Since the spinal and peripheral nervous systems of NBI-treated rats are known to
differ from normal rats, the present experiments sought to determine whether a
supraspinal nervous system structure, the central amygdala, is still necessary
for the induction of Acute Footshock-induced hypersensitivity. The effect of
bilateral amygdala electrolytic lesions on Acute Footshock-induced bladder
hypersensitivity in adult female rats was tested in Control rats which underwent
a control protocol as neonates and in experimental rats which experienced NBI.
Consistent with our previous report, in Control rats, Acute Footshock-induced
bladder hypersensitivity was eliminated by bilateral Amygdala Lesions. In
contrast, Acute Footshock-induced bladder hypersensitivity in NBI-treated rats
was unaffected by bilateral Amygdala Lesions. These findings provide evidence
that NBI results in the recruitment of substrates of bladder hypersensitivity
that may differ from those of normal rats. This, in turn, suggests that unique
therapeutics may be needed for painful bladder disorders like interstitial
cystitis.
PMID- 29964028
TI - Selection of DNA aptamers to Streptococcus pneumonia and fabrication of graphene
oxide based fluorescent assay.
AB - Pneumococci are one of the leading causes of infections throughout the world
causing problems mainly in children, elderly, and immune-deficient patients. In
recent years antibiotic resistant Streptococcus pneumoniae strains become
widespread. Therefore simple, rapid, and specific detection methods are needed
for public health. In this study, DNA aptamer probes against S. pneumoniae were
selected using bacterial Systematic Evolution of Ligands by Exponential
Enrichment (SELEX) and these probes were integrated in to a graphene oxide (GO)
based fluorescent assay. Among the tested aptamers three candidates Lyd-1, Lyd-2
and Lyd-3 showed Kd values of 844.7 +/- 123.6, 1984.8 +/- 347.5, and 661.8 +/-
111.3 nM, respectively. These candidates showed binding affinity to S. pneumoniae
and no specific binding to the bacteria used in negative selection. The binding
of aptamers were showed by fluorescence spectroscopy and flow cytometry. GO based
label-free fluorescent assay developed using Lyd-3 aptamer had a unique detection
limit of 15 cfu mL-1. Thus we believe that the selected aptamers and fabricated
GO based assay has potential to be used in the detection of S. pneumoniae.
Selected aptamers selectively bind to S. pneumonia with anti-pneumococcal
potential and holds great potential to be used as molecular probes for
identifying and targeting.
PMID- 29964026
TI - Mouse but not zebrafish requires retinoic acid for control of neuromesodermal
progenitors and body axis extension.
AB - In mouse, retinoic acid (RA) is required for the early phase of body axis
extension controlled by a population of neuromesodermal progenitors (NMPs) in the
trunk called expanding-NMPs, but not for the later phase of body axis extension
controlled by a population of NMPs in the tail called depleting-NMPs. Recent
observations suggest that zebrafish utilize depleting-NMPs but not expanding-NMPs
for body axis extension. In zebrafish, a role for RA in body axis extension was
not supported by previous studies on aldh1a2 (raldh2) mutants lacking RA
synthesis. Here, by treating zebrafish embryos with an RA synthesis inhibitor, we
also found that body axis extension and somitogenesis was not perturbed, although
loss of pectoral fin and cardiac edema were observed consistent with previous
studies. The conclusion that zebrafish diverges from mouse in not requiring RA
for body axis extension is consistent with zebrafish lacking early expanding-NMPs
to generate the trunk. We suggest that RA control of body axis extension was
added to higher vertebrates during evolution of expanding-NMPs.
PMID- 29964027
TI - A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice.
AB - The FGF/ERK signaling pathway is highly conserved throughout evolution and plays
fundamental roles during embryonic development and in adult organisms. While a
plethora of expression data exists for ligands, receptors and pathway regulators,
we know little about the spatial organization or dynamics of signaling in
individual cells within populations. To this end we developed a transcriptional
readout of FGF/ERK activity by targeting a histone H2B-linked Venus fluorophore
to the endogenous locus of Spry4, an early pathway target, and generated Spry4H2B
Venus embryonic stem cells (ESCs) and a derivative mouse line. The Spry4H2B-Venus
reporter was heterogeneously expressed within ESC cultures and responded to
FGF/ERK signaling manipulation. In vivo, the Spry4H2B-Venus reporter
recapitulated the expression pattern of Spry4 and localized to sites of known
FGF/ERK activity including the inner cell mass of the pre-implantation embryo and
the limb buds, somites and isthmus of the post-implantation embryo. Additionally,
we observed highly localized reporter expression within adult organs. Genetic and
chemical disruption of FGF/ERK signaling, in vivo in pre- and post-implantation
embryos, abrogated Venus expression establishing the reporter as an accurate
signaling readout. This tool will provide new insights into the dynamics of the
FGF/ERK signaling pathway during mammalian development.
PMID- 29964029
TI - Rapid method for an enhanced recovery of biologically active human phospholipid
scramblase1 from inclusion bodies.
AB - Human phospholipid scramblase 1 (hPLSCR1) is an ATP independent, Ca2+ dependent
transmembrane protein mediating bidirectional translocation of phospholipids
across the lipid bilayer but the mechanism of scrambling is unknown.
Determination of the hPLSCR1 structure would help understand the mechanism and
its multi-functional property. Recombinant hPLSCR1 forms inclusion bodies (IBs),
when over-expressed in E. coli BL21 (DE3) and recovery of active hPLSCR1 from
IBs, were time-consuming and resulted in low protein yield. This study aims to
optimize and enhance the expression and purification of active recombinant
hPLSCR1 by various strategies. Additives including stabilizers and detergents
were added during cell lysis to improve the recovery of soluble hPLSCR1. Five E.
coli strains, BL21 (DE3), C43 (DE3), Rosetta, BL21-CodonPlus-RP, and BL21 (DE3)
pLysS were screened for maximum yield of soluble protein but localized in IBs. To
recover hPLSCR1 from IBs, different additives were added of which, 0.3% N-lauroyl
sarcosine (NLS) recovered ~50% of bioactive hPLSCR1 from IBs. E. coli C43 (DE3)
gave higher yields of purified protein (7.76 mg/g cell) followed by E. coli BL21
(DE3) pLysS (5.87 mg/g cell). This report describes a rapid and efficient method
for solubilizing membrane proteins from inclusion bodies with a higher recovery.
PMID- 29964030
TI - A surface plasmon resonance based inhibition immunoassay for measurement of
steroid hormones.
AB - Quantitative measurement of small-molecule metabolites is now emerging as an
effective way to link the metabolite profile to disease state. Surface plasmon
resonance (SPR) is a sensing platform that has demonstrated applicability for a
large range of biomolecules. However, direct detection of small molecules with
SPR challenges the refractive index based detection mechanism. Herein, we
utilized an indirect detection format and developed an inhibition immunoassay for
the quantitative measurement of 17beta-estradiol (E2) using SPR. One competitor,
BSA-E2 conjugate, was immobilized to the SPR chip via the reaction between the
primary amino group of the conjugate and the succinimide group (NHS) introduced
by the formation of a thiol-NHS monolayer on gold surface. Free E2 molecules
compete with BSA-E2 on chip surface for binding sites provided by a monoclonal
anti-E2 antibody. It was found the binding affinity of the antibody to BSA-E2
conjugate increases with decreasing surface coverage of BSA-E2 conjugate. Under
optimal conditions, a sigmoidal calibration curve with a negative slope and a
dynamic range from 10 pM to 2 nM was generated. The detection limit of the
immunoassay is estimated to be 0.3 pM. Moreover, the immunoassay exhibits high
specificity for E2 detection using estrone (E1) as a potential interference.
PMID- 29964031
TI - Editorial for Analytical Biochemistry special issue on RPA.
PMID- 29964032
TI - The Anti-Inflammatory Activities of Propionibacterium acnes CAMP Factor-Targeted
Acne Vaccines.
AB - Inflammatory acne vulgaris afflicts hundreds of millions of people globally.
Propionibacterium acnes, an opportunistic skin bacterium, has been linked to the
pathogenesis of acne vulgaris. Our results show that a secretory Christie-Atkins
Munch-Petersen (CAMP) factor of P. acnes is up-regulated in anaerobic cultures.
Mutation of CAMP factor significantly diminishes P. acnes colonization and
inflammation in mice, demonstrating the essential role of CAMP factor in the
cytotoxicity of P. acnes. Vaccination of mice with CAMP factor considerably
reduced the growth of P. acnes and production of MIP-2, a murine counterpart of
human IL-8. Acne lesions were collected from patients to establish an ex vivo
acne model for validation of the efficacy of CAMP factor antibodies in the
neutralization of the acne inflammatory response. The P. acnes CAMP factor and
two proinflammatory cytokines (IL-8 and IL-1beta) were expressed at higher levels
in acne lesions than those in nonlesional skin. Incubation of ex vivo acne
explants with monoclonal antibodies to CAMP factor markedly attenuated the
amounts of IL-8 and IL-1beta. Our work using an ex vivo acne model shows that P.
acnes CAMP factor is an essential source of inflammation in acne vulgaris.
PMID- 29964033
TI - Detection of HPV E7 Transcription at Single-Cell Resolution in Epidermis.
AB - Persistent human papillomavirus (HPV) infection is responsible for at least 5% of
human malignancies. Most HPV-associated cancers are initiated by the HPV16
genotype, as confirmed by detection of integrated HPV DNA in cells of oral and
anogenital epithelial cancers. However, single-cell RNA sequencing may enable
prediction of HPV involvement in carcinogenesis at other sites. We conducted
single-cell RNA sequencing on keratinocytes from a mouse transgenic for the E7
gene of HPV16 and showed sensitive and specific detection of HPV16-E7 mRNA,
predominantly in basal keratinocytes. We showed that increased E7 mRNA copy
number per cell was associated with increased expression of E7 induced genes.
This technique enhances detection of active viral transcription in solid tissue
and may clarify possible linkage of HPV infection to development of squamous cell
carcinoma.
PMID- 29964034
TI - Eosinophils Determine Dermal Thickening and Water Loss in an MC903 Model of
Atopic Dermatitis.
AB - Atopic dermatitis (AD) is a highly debilitating disease with significant health
impacts worldwide. It has been a difficult disease to treat because of the wide
spectrum of clinical manifestations. Therefore, the current clinical management
strategies are nonspecific. Previous studies have documented that AD disease
progression is precipitated by a combination of skin barrier dysfunction, itch,
and immune dysregulation. However, the precise roles played by effector cells and
cytokines have not been fully elucidated. To address this, we established a
prolonged model of AD, using MC903. The phenotype of this MC903 model closely
resembles the one observed in AD patients, including inflammatory parameters,
barrier dysfunction, itch, and histopathological characteristics, thereby
providing a platform to evaluate targets for the treatment of AD. This model
exposed cells and cytokines that are critically associated with disease severity,
including eosinophils, TSLP, and IL-4/IL-13. Indeed, eosinophil depletion
significantly ameliorated AD pathology, most notably barrier dysfunction, to a
similar extent as blocking of the IL-4/IL-13 axis by genetic deletion of STAT6.
Thus, this study has identified eosinophils to be critical for the development
and maintenance of AD, thereby proposing these effector cells as therapeutic
targets for the treatment of AD.
PMID- 29964035
TI - How to Approach Difficult Patient Encounters: ROAR.
PMID- 29964036
TI - Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory
Helicobacter pylori Infection.
AB - BACKGROUND & AIMS: We aimed to compare the efficacy of genotypic resistance
guided therapy vs empirical therapy for eradication of refractory Helicobacter
pylori infection in randomized controlled trials. METHODS: We performed 2
multicenter, open-label trials of patients with H pylori infection (20 years or
older) failed by 2 or more previous treatment regimens, from October 2012 through
September 2017 in Taiwan. The patients were randomly assigned to groups given
genotypic resistance-guided therapy for 14 days (n = 21 in trial 1, n = 205 in
trial 2) or empirical therapy according to medication history for 14 days (n = 20
in trial 1, n = 205 in trial 2). Patients received sequential therapy containing
esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and
metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in
trial 1, tetracycline in trial 2) for another 7 days (all given twice daily)
based on genotype markers of resistance determined from gastric biopsy specimens
(group A) or empirical therapy according to medication history. Resistance
associated mutations in 23S ribosomal RNA or gyrase A were identified by
polymerase chain reaction with direct sequencing. Eradication status was
determined by 13C-urea breath test. The primary outcome was eradication rate.
RESULTS: H pylori infection was eradicated in 17 of 21 (81%) patients receiving
genotype resistance-guided therapy and 12 of 20 (60%) patients receiving
empirical therapy (P = .181) in trial 1. This trial was terminated ahead of
schedule due to the low rate of eradication in patients given doxycycline
sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was
eradicated in 160 of 205 (78%) patients receiving genotype resistance-guided
therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170),
according to intent to treat analysis. The frequencies of adverse effects and
compliance did not differ significantly between groups. CONCLUSIONS: Properly
designed empirical therapy, based on medication history, is an acceptable
alternative to genotypic resistance-guided therapy for eradication of refractory
H pylori infection after consideration of accessibility, cost, and patient
preference. ClinicalTrials.gov ID: NCT01725906.
PMID- 29964037
TI - Past Questions and Current Understanding About Gastric Cancer.
PMID- 29964038
TI - Vitamin D Regulation of the Uridine Phosphorylase 1 Gene and Uridine-Induced DNA
Damage in Colon in African Americans and European Americans.
AB - BACKGROUND & AIMS: African Americans have the greatest colorectal cancer (CRC)
burden in the United States; interethnic differences in protective effects of
vitamin D might contribute to disparities. 1alpha,25(OH)2D3 vitamin D (the active
form of vitamin D) induces transcription of the uridine phosphorylase gene (UPP1)
in colon tissues of European Americans but to a lesser extent in colon tissues of
African Americans. UPP1-knockout mice have increased intestinal concentrations of
uridine and Deoxyuridine triphosphate (dUTP), have increased uridine-induced DNA
damage, and develop colon tumors. We studied 1alpha,25(OH)2D3 regulation of UPP1
and uridine-induced DNA damage in the colon and differences in these processes
between African and European Americans. METHODS: We quantified expression and
activity of UPP1 in response to 1alpha,25(OH)2D3 in young adult mouse colonic
cells, human CRC cells (LS174T), and organoids (derived from rectosigmoid biopsy
samples of healthy individuals undergoing colonoscopies) using quantitative
polymerase chain reaction, immunoblot, and immunocytochemistry assays. Binding of
the vitamin D receptor to UPP1 was tested by chromatin immunoprecipitation.
Uridine-induced DNA damage was measured by fragment-length analysis in repair
enzyme assays. Allele-specific 1alpha,25(OH)2D3 responses were tested using
luciferase assays. RESULTS: Vitamin D increased levels of UPP1 mRNA, protein, and
enzymatic activity and increased vitamin D receptor binding to the UPP1 promoter
in young adult mouse colonic cells, LS174T cells, and organoids. 1alpha,25(OH)2D3
significantly reduced levels of uridine and uridine-induced DNA damage in these
cells, which required UPP1 expression. Organoids derived from colon tissues of
African Americans expressed lower levels of UPP1 after exposure to
1alpha,25(OH)2D3 and had increased uridine-induced DNA damage compared with
organoids derived from tissues of European Americans. Luciferase assays with the
T allele of single nucleotide polymorphism rs28605337 near UPP1, which is found
more frequently in African Americans than European Americans, expressed lower
levels of UPP1 after exposure to 1alpha,25(OH)2D3 than assays without this
variant. CONCLUSIONS: We found vitamin D to increase expression of UPP1, leading
to reduce uridine-induced DNA damage, in colon cells and organoids. A
polymorphism in UPP1 found more frequently in African Americans than European
Americans reduced UPP1 expression upon cell exposure to 1alpha,25(OH)2D3.
Differences in expression of UPP1 in response to vitamin D could contribute to
the increased risk of CRC in African Americans.
PMID- 29964039
TI - How to Ensure Patient Adherence to Colorectal Cancer Screening and Surveillance
in Your Practice.
PMID- 29964041
TI - Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut
Disorders.
AB - Prebiotics and diets low in fermentable oligo-, di-, mono-saccharides and polyols
(low-FODMAP diet) might reduce symptoms in patients with functional
gastrointestinal disorders, despite reports that some nonabsorbable, fermentable
meal products (prebiotics) provide substrates for colonic bacteria and thereby
increase gas production. We performed a randomized, parallel, double-blind study
of patients with functional gastrointestinal disorders with flatulence. We
compared the effects of a prebiotic supplement (2.8 g/d Bimuno containing 1.37 g
beta-galactooligosaccharide) plus a placebo (Mediterranean-type diet (prebiotic
group, n = 19) vs a placebo supplement (2.8 g xylose) plus a diet low in FODMAP
(low-FODMAP group, n = 21) for 4 weeks; patients were then followed for 2 weeks.
The primary outcome was effects on composition of the fecal microbiota, analyzed
by 16S sequencing. Secondary outcomes were intestinal gas production and
digestive sensations. After 4 weeks, we observed opposite effects on microbiota
in each group, particularly in relation to the abundance of Bifidobacterium
sequences (increase in the prebiotic group and decrease in the low-FODMAP group;
P = .042), and Bilophila wadsworthia (decrease in the prebiotic group and
increase in the low-FODMAP group; P = .050). After 4 weeks, both groups had
statistically significant reductions in all symptom scores, except reductions in
flatulence and borborygmi were not significant in the prebiotic group. Although
the decrease in symptoms persisted for 2 weeks after patients discontinued
prebiotic supplementation, symptoms reappeared immediately after patients
discontinued the low-FODMAP diet. Intermittent prebiotic administration might
therefore be an alternative to dietary restrictions for patients with functional
gut symptoms. ClinicalTrials.gov no.: NCT02210572.
PMID- 29964040
TI - Dysregulated Bile Transporters and Impaired Tight Junctions During Chronic Liver
Injury in Mice.
AB - BACKGROUND & AIMS: Liver fibrosis, hepatocellular necrosis, inflammation, and
proliferation of liver progenitor cells are features of chronic liver injury.
Mouse models have been used to study the end-stage pathophysiology of chronic
liver injury. However, little is known about differences in the mechanisms of
liver injury among different mouse models because of our inability to visualize
the progression of liver injury in vivo in mice. We developed a method to
visualize bile transport and blood-bile barrier (BBlB) integrity in live mice.
METHODS: C57BL/6 mice were fed a choline-deficient, ethionine-supplemented (CDE)
diet or a diet containing 0.1% 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC)
for up to 4 weeks to induce chronic liver injury. We used quantitative liver
intravital microscopy (qLIM) for real-time assessment of bile transport and BBlB
integrity in the intact livers of the live mice fed the CDE, DDC, or chow
(control) diets. Liver tissues were collected from mice and analyzed by
histology, immunohistochemistry, real-time polymerase chain reaction, and
immunoblots. RESULTS: Mice with liver injury induced by a CDE or a DDC diet had
breaches in the BBlB and impaired bile secretion, observed by qLIM compared with
control mice. Impaired bile secretion was associated with reduced expression of
several tight-junction proteins (claudins 3, 5, and 7) and bile transporters
(NTCP, OATP1, BSEP, ABCG5, and ABCG8). A prolonged (2-week) CDE, but not DDC,
diet led to re-expression of tight junction proteins and bile transporters,
concomitant with the reestablishment of BBlB integrity and bile secretion.
CONCLUSIONS: We used qLIM to study chronic liver injury, induced by a choline
deficient or DDC diet, in mice. Progression of chronic liver injury was
accompanied by loss of bile transporters and tight junction proteins.
PMID- 29964042
TI - Are We Close to Targeting Enteric Glia in Gastrointestinal Diseases and Motility
Disorders?
PMID- 29964044
TI - Molecular Visualization on the Holodeck.
AB - Can virtual reality be useful for visualizing and analyzing molecular structures
and three-dimensional (3D) microscopy? Uses we are exploring include studies of
drug binding to proteins and the effects of mutations, building accurate atomic
models in electron microscopy and x-ray density maps, understanding how immune
system cells move using 3D light microscopy, and teaching schoolchildren about
biomolecules that are the machinery of life. Virtual reality (VR) offers
immersive display with a wide field of view and head tracking for better
perception of molecular architectures and uses 6-degree-of-freedom hand
controllers for simple manipulation of 3D data. Conventional computer displays
with trackpad, mouse and keyboard excel at two-dimensional tasks such as writing
and studying research literature, uses for which VR technology is at present far
inferior. Adding VR to the conventional computing environment could improve 3D
capabilities if new user-interface problems can be solved. We have developed
three VR applications: ChimeraX for analyzing molecular structures and electron
and light microscopy data, AltPDB for collaborative discussions around atomic
models, and Molecular Zoo for teaching young students characteristics of
biomolecules. Investigations over three decades have produced an extensive
literature evaluating the potential of VR in research and education. Consumer VR
headsets are now affordable to researchers and educators, allowing direct tests
of whether the technology is valuable in these areas. We survey here advantages
and disadvantages of VR for molecular biology in the context of affordable and
dramatically more powerful VR and graphics hardware than has been available in
the past.
PMID- 29964045
TI - Hexapeptide Tandem Repeats Dictate the Formation of Silkmoth Chorion, a Natural
Protective Amyloid.
AB - Silkmoth chorion is a fibrous structure composed mainly of two major protein
classes, families A and B. Both families of silkmoth chorion proteins present a
highly conserved, in sequence and in length, central domain, consisting of Gly
rich tandem hexapeptide repetitive segments, flanked by two more variable N
terminal and C-terminal arms. Primary studies identified silkmoth chorion as a
functional protective amyloid by unveiling the amyloidogenic properties of the
central domain of both protein families. In this work, we attempt to detect the
principal source of amyloidogenicity of the central domain by focusing on the
role of the tandem hexapeptide sequence repeats. Concurrently, we discuss a
possible mechanism for the self-assembly of class A protofilaments, suggesting
that the aggregation-prone hexapeptide building blocks may fold into a triangle
shaped beta-helical structure.
PMID- 29964043
TI - Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or
Remission in Ulcerative Colitis.
AB - BACKGROUND & AIMS: Parenteral methotrexate induces clinical remission but not
endoscopic improvement of mucosal inflammation in patients with ulcerative
colitis (UC). We performed a randomized, placebo-controlled trial to assess the
efficacy of parenteral methotrexate in maintaining steroid-free response or
remission in patients with UC after induction therapy with methotrexate and
steroids. METHODS: We performed a 48-week trial, from February 2012 through May
2016, of 179 patients with active UC (Mayo score of 6-12 with endoscopy subscore
>= 2) despite previous conventional or biological therapy. The study comprised a
16-week open label methotrexate induction period followed by a 32-week double
blind, placebo-controlled maintenance period. Patients were given subcutaneous
methotrexate (25 mg/wk) and a 12-week steroid taper. At week 16, steroid-free
responders were randomly assigned to groups that either continued methotrexate
(25 mg/wk, n = 44) or were given placebo (n = 40) until week 48. We compared the
efficacy of treatment by analyzing the proportion of patients who remained
relapse free and were in remission at week 48 without use of steroids or other
medications to control disease activity. RESULTS: Ninety-one patients (51%)
achieved response at week 16, and 84 patients were included in the maintenance
period study. During this period, 60% of patients in the placebo group (24/40)
and 66% in the methotrexate group (29/44) had a relapse of UC (P = .75). At week
48, 30% of patients in the placebo group (12/40) and 27% of patients in the
methotrexate group (12/44) were in steroid-free clinical remission without need
for additional therapies (P = .86). No new safety signals for methotrexate were
detected. CONCLUSIONS: Parenteral methotrexate (25 mg/wk) was not superior to
placebo in preventing relapses of UC in patients who achieved steroid-free
response during induction therapy. ClinicalTrials.gov, Number: NCT01393405.
PMID- 29964046
TI - beta-Sheet Augmentation Is a Conserved Mechanism of Priming HECT E3 Ligases for
Ubiquitin Ligation.
AB - Ubiquitin (Ub) ligases (E3s) catalyze the attachment of Ub chains to target
proteins and thereby regulate a wide array of signal transduction pathways in
eukaryotes. In HECT-type E3s, Ub first forms a thioester intermediate with a
strictly conserved Cys in the C-lobe of the HECT domain and is then ligated via
an isopeptide bond to a Lys residue in the substrate or a preceding Ub in a poly
Ub chain. To date, many key aspects of HECT-mediated Ub transfer have remained
elusive. Here, we provide structural and functional insights into the catalytic
mechanism of the HECT-type ligase Huwe1 and compare it to the unrelated, K63
specific Smurf2 E3, a member of the Nedd4 family. We found that the Huwe1 HECT
domain, in contrast to Nedd4-family E3s, prioritizes K6- and K48-poly-Ub chains
and does not interact with Ub in a non-covalent manner. Despite these mechanistic
differences, we demonstrate that the architecture of the C-lobe~Ub intermediate
is conserved between Huwe1 and Smurf2 and involves a reorientation of the very C
terminal residues. Moreover, in Nedd4 E3s and Huwe1, the individual sequence
composition of the Huwe1 C-terminal tail modulates ubiquitination activity,
without affecting thioester formation. In sum, our data suggest that catalysis of
HECT ligases hold common features, such as the beta-sheet augmentation that
primes the enzymes for ligation, and variable elements, such as the sequence of
the HECT C-terminal tail, that fine-tune ubiquitination activity and may aid in
determining Ub chain specificity by positioning the substrate or acceptor Ub.
PMID- 29964047
TI - Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in
Pseudomonas aeruginosa Biofilms.
AB - Amyloids are typically associated with neurodegenerative diseases, but recent
research demonstrates that several bacteria utilize functional amyloid fibrils to
fortify the biofilm extracellular matrix and thereby resist antibiotic
treatments. In Pseudomonas aeruginosa, these fibrils are composed predominantly
of FapC, a protein with high-sequence conservation among the genera. Previous
studies established FapC as the major amyloid subunit, but its mechanism of
fibril formation in P. aeruginosa remained largely unexplored. Here, we examine
the FapC sequence in greater detail through a combination of bioinformatics and
protein engineering, and we identify specific motifs that are implicated in
amyloid formation. Sequence regions of high evolutionary conservation tend to
coincide with regions of high amyloid propensity, and mutation of amyloidogenic
motifs to a designed, non-amyloidogenic motif suppresses fibril formation in a pH
dependent manner. We establish the particular significance of the third repeat
motif in promoting fibril formation and also demonstrate emergence of soluble
oligomer species early in the aggregation pathway. The insights reported here
expand our understanding of the mechanism of amyloid polymerization in P.
aeruginosa, laying the foundation for development of new amyloid inhibitors to
combat recalcitrant biofilm infections.
PMID- 29964049
TI - Early Virus-Host Cell Interactions.
PMID- 29964048
TI - Mapping Conformational Dynamics to Individual Steps in the TEM-1 beta-Lactamase
Catalytic Mechanism.
AB - Conformational dynamics are increasingly recognized as being essential for enzyme
function. However, there is virtually no direct experimental evidence to support
the notion that individual dynamic modes are required for specific catalytic
processes, apart from the initial step of substrate binding. In this work, we use
a unique approach based on millisecond hydrogen-deuterium exchange mass
spectrometry to identify dynamic modes linked to individual catalytic processes
in the antibiotic resistance enzyme TEM-1 beta-lactamase. Using a "good"
substrate (ampicillin), a poorly hydrolyzed substrate (cephalexin) and a covalent
inhibitor (clavulanate), we are able to isolate dynamic modes that are
specifically linked to substrate binding, productive lactam ring hydrolysis and
deacylation. These discoveries are ultimately translated into specific targets
for allosteric TEM-1 inhibitor development.
PMID- 29964050
TI - Genetic and epigenetic changes in clonal descendants of irradiated human
fibroblasts.
AB - To study delayed genetic and epigenetic radiation effects, which may trigger
radiation-induced carcinogenesis, we have established single-cell clones from
irradiated and non-irradiated primary human fibroblasts. Stable clones were
endowed with the same karyotype in all analyzed metaphases after 20 population
doublings (PDs), whereas unstable clones displayed mosaics of normal and abnormal
karyotypes. To account for variation in radiation sensitivity, all experiments
were performed with two different fibroblast strains. After a single X-ray dose
of 2 Gy more than half of the irradiated clones exhibited radiation-induced
genome instability (RIGI). Irradiated clones displayed an increased rate of loss
of chromosome Y (LOY) and copy number variations (CNVs), compared to controls.
CNV breakpoints clustered in specific chromosome regions, in particular 3p14.2
and 7q11.21, coinciding with common fragile sites. CNVs affecting the FHIT gene
in FRA3B were observed in independent unstable clones and may drive RIGI.
Bisulfite pyrosequencing of control clones and the respective primary culture
revealed global hypomethylation of ALU, LINE-1, and alpha-satellite repeats as
well as rDNA hypermethylation during in vitro ageing. Irradiated clones showed
further reduced ALU and alpha-satellite methylation and increased rDNA
methylation, compared to controls. Methylation arrays identified several hundred
differentially methylated genes and several enriched pathways associated with in
vitro ageing. Methylation changes in 259 genes and the MAP kinase signaling
pathway were associated with delayed radiation effects (after 20 PDs).
Collectively, our results suggest that both genetic (LOY and CNVs) and epigenetic
changes occur in the progeny of exposed cells that were not damaged directly by
irradiation, likely contributing to radiation-induced carcinogenesis. We did not
observe epigenetic differences between stable and unstable irradiated clones. The
fact that the DNA methylation (DNAm) age of clones derived from the same primary
culture varied greatly suggests that DNAm age of a single cell (represented by a
clone) can be quite different from the DNAm age of a tissue. We propose that DNAm
age reflects the emergent property of a large number of individual cells whose
respective DNAm ages can be highly variable.
PMID- 29964051
TI - Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes
wound healing via the PI3K/Akt signaling pathway.
AB - INTRODUCTION: Adipose tissue-derived stem cells (ADSCs) have been shown to
enhance wound healing via their paracrine function. Exosomes, as one of the most
important paracrine factors, play an essential role in this process. However, the
concrete mechanisms that underlie this effect are poorly understood. In this
study, we aim to explore the potential roles and molecular mechanisms of exosomes
derived from ADSCs in cutaneous wound healing. METHODS: Normal human skin
fibroblasts and ADSCs were isolated from patient skin and adipose tissues. ADSCs
were characterized by using flow cytometric analysis and adipogenic and
osteogenic differentiation assays. Exosomes were purified from human ADSCs by
differential ultracentrifugation and identified by electron microscopy,
nanoparticle tracking, fluorescence confocal microscopy and western blotting.
Fibroblasts were treated with different concentrations of exosomes, and the
synthesis of collagen was analyzed by western blotting; the levels of growth
factors were analyzed by real-time quantitative PCR (RT-PCR) and ELISA; and the
proliferation and migration abilities of fibroblasts were analyzed by real-time
cell analysis, CCK-8 assays and scratch assays. A mouse model with a full
thickness incision wound was used to evaluate the effect of ADSC-derived exosomes
on wound healing. The level of p-Akt/Akt was analyzed by western blotting.
Ly294002, a phosphatidylinositol 3-kinases (PI3K) inhibitor, was used to identify
the underlying mechanisms by which ADSC-derived exosomes promote wound healing.
RESULTS: ADSC-derived exosomes were taken up by the fibroblasts, which showed
significant, dose-dependent increases in cell proliferation and migration
compared to the behavior of cells without exosome treatment. More importantly,
both the mRNA and protein levels of type I collagen (Col 1), type III collagen
(Col 3), MMP1, bFGF, and TGF-beta1 were increased in fibroblasts after
stimulation with exosomes. Furthermore, exosomes significantly accelerated wound
healing in vivo and increased the level of p-Akt/Akt in vitro. However, Ly294002
alleviated these exosome-induced changes, suggesting that exosomes from ADSCs
could promote and optimize collagen deposition in vitro and in vivo and further
promote wound healing via the PI3K/Akt signaling pathway. CONCLUSIONS: This study
demonstrates that ADSC-derived exosomes can promote fibroblast proliferation and
migration and optimize collagen deposition via the PI3K/Akt signaling pathway to
further accelerate wound healing. Our results suggest that ADSCs likely
facilitate wound healing via the release of exosomes, and the PI3K/Akt pathway
may play a role in this process. Our data also suggest that the clinical
application of ADSC-derived exosomes may shed new light on the use of cell-free
therapy to accelerate full-thickness skin wound healing and attenuate scar
formation.
PMID- 29964052
TI - Resveratrol promotes oxidative stress to drive DLC1 mediated cellular senescence
in cancer cells.
AB - Induction of cellular senescence represents a novel strategy to inhibit aberrant
proliferation of cancer cells. Resveratrol is gaining attention for its cancer
preventive and suppressive properties. Tumor suppressor gene DLC1 is shown to
induce apoptosis, suppress migration and invasion in various cancer cells.
However, the function of DLC1 in cancer cellular senescence is unclear. This
study was designed to investigate the biological role of DLC1 in resveratrol
induced cancer cellular senescence. Our results showed that resveratrol inhibited
proliferation of cancer cell lines (MCF-7, MDA-MB-231 and H1299) and induced
senescence along with increase of SA-beta-gal activity and regulation of
senescence-associated molecular markers p38MAPK, p-p38MAPK, p27, p21, Rb and p-Rb
protein. The underlying mechanism was that resveratrol induced mitochondrial
dysfunction with reduction of mitochondrial membrane potential, down-regulation
of MT-ND1, MT-ND6 and ATPase8 in transcript level and down-regulation of PGC
1alpha in protein level to result in ROS production. With ROS elevation,
resveratrol decreased DNMT1 and increased DLC1 expression significantly. However,
after ROS scavenger NAC was added to the cancer cells treated by resveratrol,
DNMT1, DLC1 and senescence-associated molecular markers were reversed. This
reveals that resveratrol induced cancer cellular senescence through DLC1 in a ROS
dependent manner. Silencing DLC1 markedly attenuated SA-beta-gal activity and
p38MAPK, p27 and p21 protein levels, and increased Rb expression, indicating that
resveratrol promoted senescence via targeting DLC1. Moreover, DLC1 promoted
senescence through FoxO3a/NF-kappaB signaling mediated by SIRT1 after resveratrol
treatment. Finally, resveratrol increased ROS production to induce DNA damage
with p-CHK1 up-regulation and result in cancer cellular senescence. This is the
first time to investigate resveratrol induced cancer cellular senescence by
primarily targeting DLC1. Induction of cellular senescence by resveratrol may
represent a novel anticancer mechanism.
PMID- 29964053
TI - High expression of enhancer RNA MARC1 or its activation by DHT is associated with
the malignant behavior in bladder cancer.
AB - Enhancer RNAs (eRNAs), a subclass of noncoding RNA from enhancers, have
biological functions in gene expression. However, their potential role in bladder
cancer (BCa) remains largely unknown. The present study investigated the
functional role of androgen-associated androgen receptor (AR) mediated-eRNA MARC1
(eMARC1) in BCa progression. Cell proliferation, migration, and apoptosis of BCa
cell lines (5637 and T24) with different eMARC1 expression levels or treated with
5alpha-dehydrotestosterone (DHT) were investigated. In the current study, we
discovered that eMARC1 was highly expressed in BCa tissues and cell lines, and
eMARC1 overexpression promoted the progression of BCa cells, while knockdown of
eMARC1 suppressed tumorigenesis. DHT treatment significantly elevated eMARC1
expression levels, which also facilitated cell proliferation, motility, and
inhibited cell apoptosis. We further found that eMARC1 silencing impaired the
androgenic effect of DHT in BCa cells. These results suggested that eMARC1
exerted its effects on BCa cell progression, and DHT promoted bladder cancer
progression by activating eMARC1.
PMID- 29964054
TI - Rosiglitazone rescues human neural stem cells from amyloid-beta induced ER stress
via PPARgamma dependent signaling.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a family
of ligand-activated nuclear receptors known to regulate many crucial
physiological and pathological conditions. Indeed, altered PPARgamma
transcriptional activity contributes to metabolic syndromes (obesity and
hyperglycemia associated with type 2 diabetes mellitus), stroke and
neurodegenerative diseases. Various studies suggest that PPARgamma agonists
influence neuronal deficits in Alzheimer's Disease (AD) patients and rodent
models of AD. Expression of amyloid-beta (Abeta), a neuropathological marker
associated with the pathogenesis of AD neuronal impairment, is inversely
correlated with the activation of PPARgamma-dependent neuroprotective responses.
Nevertheless, molecular mechanisms by which the effects of PPARgamma agonists in
AD remain to be clarified. Here, we explore the PPARgamma signaling pathways and
networks that protect against Abeta-induced endoplasmic reticulum (ER) stress
(e.g., caspase 4, Bip, CHOP, ASK1 and ER calcium), cell death (e.g., viability
and cytochrome c) and mitochondrial deficiency (e.g., maximal respiratory
function, COX activity, and mitochondrial membrane potential) events in the human
neural stem cells (hNSCs) treated with Abeta. Co-treatment with GW9662 (an
antagonist of PPARgamma) effectively blocked these protective effects by
rosiglitazone, providing strong evidence that PPARgamma-dependent signaling
rescues hNSCs from Abeta-mediated toxicity. Together, our data suggest activation
of PPARgamma pathway might be critical to protecting against AD-related ER
stress, ER disequilibrium and mitochondrial deficiency. These findings also
improve our understanding of the role of PPARgamma in hNSCs, and may aid in the
development and implementation of new therapeutic strategies for the treatment of
AD.
PMID- 29964056
TI - Atopic dermatitis in Chinese patients shows TH2/TH17 skewing with psoriasiform
features.
PMID- 29964057
TI - Alternaria is associated with asthma symptoms and exhaled NO among NYC children.
PMID- 29964055
TI - C1qTNF-related protein 1 attenuates doxorubicin-induced cardiac injury via
activation of AKT.
AB - AIMS: The clinical use of doxorubicin (Dox) is limited due to a degenerative
irreversible cardiac toxicity, but the precise mechanisms that contribute to this
pathological response are not understood. C1q/TNF-related protein 1 (CTRP1),
which is a conserved protein of the C1q family, has notable metabolic and
cardiovascular functions. However, whether CTRP1 can attenuate Dox-induced
cardiac injury remains unclear. Our study aimed to investigate the effect of
CTRP1 on Dox-induced cardiotoxicity and assessed the mechanisms of this effect.
MATERIALS AND METHODS: We manipulated CTRP1 expression in the heart using in vivo
gene delivery system. Two weeks after gene delivery, the mice received a single
intraperitoneal injection of Dox (20 mg/kg) to induce cardiac injury. KEY
FINDINGS: Cardiac CTRP1 protein levels were decreased in DOX-treated mice. CTRP1
overexpression reduced plasma cardiac troponin I, restored cardiac function and
attenuated cardiomyocyte apoptosis in Dox-treated mice. CTRP1 also improved cell
viability and reduced lactate dehydrogenase release in vitro. Dox resulted in the
decreased the protein kinase B (PKB/AKT) phosphorylation, which were restored by
CTRP1 overexpression. AKT inhibition offset the inhibitory effects of CTRP1 on
myocyte apoptosis in vitro. CTRP1 lost its protection against Dox-induced cardiac
injury in mice with AKT deficiency. Furthermore, infusion of recombinant CTRP1
protein could reverse pre-established injury in heart induced by Dox treatment.
SIGNIFICANCE: In conclusion, CTRP1 protected against Dox-induced cardiotoxicity
via activation of AKT. CTRP1 has the therapeutic potential to treat Dox-induced
cardiotoxicity.
PMID- 29964058
TI - The diversity of venom components of the scorpion species Paravaejovis
schwenkmeyeri (Scorpiones: Vaejovidae) revealed by transcriptome and proteome
analyses.
AB - The recent publication of high-throughput transcriptomic and proteomic analyses
of scorpion venom glands has increased our knowledge on the biodiversity of venom
components. In this contribution, we report the transcriptome of the venom gland
and the proteome of the venom for the scorpion species Paravaejovis
schwenkmeyeri, a member of the family Vaejovidae. We report 138 annotated
transcripts encoding putative peptides/proteins with sequence identity to known
venom components available from different databases. A fingerprint analysis
containing the molecular masses of 212 components of the whole soluble venom
revealed molecular weights of approximately 700 to 13,800 Da, with most detected
proteins ranging from 1500 to 3000 Da. Amino acid sequencing of venom components
by LC-MS/MS allowed the identification of fragments from 27 peptides encoded by
transcripts found in the transcriptome analysis. Enzymatic assays conducted with
the soluble venom fraction confirmed the presence of enzymes such as
hyaluronidases and phospholipases. The database presented here increases our
general knowledge on the biodiversity of venom components from neglected non
buthid scorpions.
PMID- 29964059
TI - Revealing genetic hybridization and DNA recombination of Fasciola hepatica and
Fasciola gigantica in nuclear introns of the hybrid Fasciola flukes.
AB - Fasciola hepatica and F. gigantica are ruminant liver flukes that are found
worldwide. They can occur sympatrically and hybridize, consequently producing an
intermediate form (Fasciola sp.), especially in Africa and Asia. The bridge
intron (TkBridgeInt) and intron 4 of domain 2 (TkD2Int4) of the taurocyamine
kinase gene were cloned and sequenced from 14 F. hepatica, 18 F. gigantica, and
12 Fasciola sp. These intron regions could be used to differentiate F. hepatica
from F. gigantica and revealed genetic hybridization and DNA recombination
between F. hepatica and F. gigantica in Fasciola sp. from Japan and Bangladesh.
Two specimens of F. hepatica from Ecuador revealed cryptic diversity. A
combination of three haplotypes observed in a Fasciola sp. specimen from Japan
suggested triploidy. Thus, the intron region of the taurocyamine kinase gene is a
potential marker for detecting the hybrid status of the Fasciola flukes.
PMID- 29964060
TI - Leishmania donovani PP2C: Kinetics, structural attributes and in vitro immune
response.
AB - Most of the signaling pathways are regulated by reversible phosphorylation
dephosphorylation which involves enzymes- kinases and phosphatases. Current
knowledge about the protein phosphatases in parasites like Trypanosoma and
Leishmania is very minimal despite their enormousity. In present study, full
length ORF of Leishmania donovani PP2C was cloned into expression vector followed
by purification and molecular weight determination using Ni-NTA affinity and gel
giltration chromatography respectively. Purified LdPP2C was found to be
enzymatically active, while inhibition study suggested that sanguinarine acts as
a non-competitive inhibitor. CD and fluorescence spectroscopy results indicated
towards an adequate protein conformation from pH 3.5 to 8.5. The quenching
constant (Ksv) and free energy (DeltaG) of LdPP2C was found to be 11.1 +/- 0.2 mM
1 and 2.0 +/- 1.1 kcal mol-1 in presence of acrylamide and urea respectively. The
protein was found to elicit the innate immune functions through upregulation of
pro-inflammatory cytokines (TNF-alpha and IL-6) as well as nitric oxide
generation. Simultaneously, these cytokines were found to be fairly higher in
protein treated cells as compared to untreated cells at transcript level too.
These observations advocate that LdPP2C generates a pro-inflammatory environment
in macrophages and hence plays important role in immunomodulation. Computational
modelling showed similar three-dimensional structure and metal binding sites
present in other member of PP2C subfamily, while docking studies revealed its
interaction with substrate as well as its specific inhibitor. Our study has
provided first time reports on enzyme kinetics, structural features and immune
response inside the host macrophage of metal-dependent protein phosphatases from
a trypanosomatid parasite.
PMID- 29964061
TI - The neutral frequency spectrum of linked sites.
AB - We introduce the conditional Site Frequency Spectrum (SFS) for a genomic region
linked to a focal mutation of known frequency. An exact expression for its
expected value is provided for the neutral model without recombination. Its
relation with the expected SFS for two sites, 2-SFS, is discussed. These spectra
derive from the coalescent approach of Fu (1995) for finite samples, which is
reviewed. Remarkably simple expressions are obtained for the linked SFS of a
large population, which are also solutions of the multi-allelic Kolmogorov
equations. These formulae are the immediate extensions of the well known single
site theta/f neutral SFS. Besides the general interest in these spectra, they
relate to relevant biological cases, such as structural variants and
introgressions. As an application, a recipe to adapt Tajima's D and other SFS
based neutrality tests to a non-recombining region containing a neutral marker is
presented.
PMID- 29964062
TI - TLR7 polymorphism, sex and chronic HBV infection influence plasmacytoid DC
maturation by TLR7 ligands.
AB - TLR7 agonists are of high interest for the treatment of cancer, auto-immunity and
chronic viral infections. They are known to activate plasmacytoid dendritic cells
(pDCs) to produce high amounts of Type I Interferon (IFN) and to facilitate T and
B cell responses, the latter with the help of maturation markers such as CD40,
CD80 and CD86. The TLR7 single nucleotide polymorphism (SNP) rs179008 (GLn11Leu),
sex and chronic viral infection have all been reported to influence pDC IFN
production. It is unknown, however, whether these factors also influence pDC
phenotypic maturation and thereby IFN-independent pDC functions. Furthermore, it
is unclear whether SNP rs179008 influences HBV susceptibility and/or clearance.
Here we investigated whether the SNP rs179008, sex and HBV infection affected
phenotypic maturation of pDCs from 38 healthy individuals and 28 chronic HBV
patients. In addition, we assessed SNP prevalence in a large cohort of healthy
individuals (n = 231) and chronic HBV patients (n = 1054). Consistent with
previous reports, the rs179008 variant allele was largely absent in Asians and
more prevalent in Caucasians. Among Caucasians, the SNP was equally prevalent in
healthy and chronically infected males. The SNP was, however, significantly more
prevalent in healthy females than in those with chronic HBV infection (42 versus
28%), suggesting that in females it may offer protection from chronic infection.
Ex vivo experiments demonstrated that induction of the co-stimulatory molecules
CD40 and CD86 by TLR7 ligands, but not TLR9 ligands, was augmented in pDCs from
healthy SNP-carrying females. Furthermore, CD80 and CD86 upregulation was more
pronounced in females independent of the SNP. Lastly, our data suggested that
chronic HBV infection impairs pDC maturation. These findings provide insight into
factors determining TLR7 responses, which is important for further clinical
development of TLR7-based therapies.
PMID- 29964064
TI - Impact of the cross-talk between circular and messenger RNAs on cell regulation.
AB - Circular RNAs (circRNA) are non-coding RNAs characterized by a closed-loop
structure providing increased stability and enhancing their ability to compete
with messenger RNAs (mRNA) for microRNA (miRNA) binding. An important open
question is if circRNA plays a physiological role in the cells regulating
critical cellular functions. We address this question with a combination of
theoretical modeling and experimental analysis. Theoretically, we investigated
two possible scenarios, one in which circRNAs act as sponges for miRNAs but there
is no other relation between the two RNAs and the other one where circRNAs are co
generated with their corresponding mRNAs. We thus compared the results with data
reporting the level of circRNAs (ZEB1, CANCX, ABCC1) modulating specific miRNAs
in 27 cell lines. Due to the high stability of circRNAs, we show that a miRNA
mediated cross-talk between circRNA and mRNA appears for a broad range of
physiological parameters. This confirms the relevance of circRNAs in cell
regulation, suggesting that they could be used as biomarkers.
PMID- 29964063
TI - Decoration of virus-like particles with an enzymatic activity of biomedical
interest.
AB - The natural properties of virus-like particles (VLPs), like their nanometric
size, polyvalence, monodispersity and biocompatibility, had called the attention
of scientists from different fields. VLPs constitute an excellent platform for
the development nanomaterials with a broad spectrum of applications, ranging from
physics of soft matter to the development of vaccines and biological
nanocarriers. To expand the repertoire of functions of VLPs, they can be
decorated with different molecules. In this research, the alpha-glucosidase Ima1p
of Saccharomyces cerevisiae was attached to the surface of in vitro assembled
VLPs of parvovirus B19, by using the SpyTag/SpyCatcher system. The resulting
particles were structurally characterized displaying a noticeable increase in
size compared to the non-decorated VLPs. The study of the biochemical properties
of the coupled enzyme indicate that it increased its Vmax by three-fold toward p
nitrophenyl-alpha-D-glucopyranoside (p-NPG) as substrate. In addition, the linked
enzyme displayed a notorious 10 degrees C shift in its optimal temperature, from
35 degrees C for the non-attached enzyme, to 45 degrees C for the enzyme
attached to VLPs. The decorated VLPs were also able to act on glycogen;
therefore, these particles may be further developed as part of the therapy for
treatment of lysosomal storage diseases derived from defects in the human acid
alpha-glucosidase.
PMID- 29964065
TI - Information sharing for a coordination game in fluctuating environments.
AB - Collective action dilemmas pervade the social and biological sciences - from
human decision-making to bacterial quorum sensing. In these scenarios,
individuals sense cues from the environment to adopt a suitable phenotype or
change in behavior. However, when cues include signals from other individuals,
then the appropriate behavior of each individual is linked. Here, we develop a
framework to quantify the influence of information sharing on individual behavior
in the context of two player coordination games. In this framework, the
environment stochastically switches between two states, and the state determines
which one of two actions players must coordinate on. Given a stochastically
switching environment, we then consider two versions of the game that differ in
the way players acquire information. In the first model, players independently
sense private environmental cues, but do not communicate with each other. We find
there are two types of strategies that emerge as Nash equilibria and fitness
maximizers - players prefer to commit to one particular action when private
information is poor, or prefer to employ phenotypic plasticity when it is good.
The second model adds an additional layer of communication, where players share
social cues as well. When the quality of social information is high, we find the
socially optimal strategy is a novel "majority logic" strategy that bases
decision-making on social cues. Our game-theoretic approach offers a principled
way of investigating the role of communication in group decision-making under
uncertain conditions.
PMID- 29964066
TI - Exercise in cirrhosis: Translating evidence and experience to practice.
AB - Physical inactivity, sarcopenia, and frailty are highly prevalent, independent
predictors of morbidity and mortality in patients with cirrhosis. Across a range
of chronic diseases, exercise training is a key recommendation supported by
guidelines and, for some conditions, even by governmental funding of exercise
programmes. Consistent with the broader chronic disease literature, the evidence
for a benefit of exercise in cirrhosis is promising. Several small trials have
reported significant improvements in muscle health (mass, strength, functional
capacity), quality of life, fatigue, and reductions in the hepatic venous
pressure gradient, without adverse events. With strong emerging evidence
surrounding the substantial risks of sarcopenia/frailty and our first-hand
experiences with liver pre-transplant exercise programmes, we contend that
routine patient care in cirrhosis should include an exercise prescription. Some
clinicians may lack the resources and necessary background to translate the
existing evidence into a practicable intervention. Our team, comprised of
physiotherapists, exercise physiologists, hepatologists, transplant specialists,
and knowledge translation experts from six North American centres, has distilled
the essential background information, tools, and practices into a set of
information ready for immediate implementation into clinics ranging from a family
practice setting to specialty cirrhosis clinics. Augmenting the rationale and
evidence are supplementary materials including video and downloadable materials
for both patients and the physician. Supporting the exercising patient is a
section regarding information about nutrition, providing practical tips suitable
for all patients with cirrhosis.
PMID- 29964067
TI - Overview of Epidemiology and Contribution of Obesity and Body Fat Distribution to
Cardiovascular Disease: An Update.
AB - Obesity is recognized as a heterogeneous condition in which individuals with
similar body mass index may have distinct metabolic and cardiovascular risk
profiles. Susceptibility to obesity-related cardiometabolic complications is not
solely mediated by overall body fat mass, but is largely dependent upon
individual differences in regional body fat distribution and ability of
subcutaneous adipose tissue to expand. The present review will discuss to what
extent the individual variation in body fat distribution is one of the clinical
key variables explaining the metabolic heterogeneity of obesity and its related
cardiovascular risk. We will present the evidence for the complex nature of the
relationship between obesity and cardiovascular disease, outline our current
understanding of the mechanisms involved, and identify future direction of
research pertinent to this interaction.
PMID- 29964068
TI - Apelin modulates murine gastric vagal afferent mechanosensitivity.
AB - Gastric vagal afferents play an important role in the peripheral control of food
intake. Apelin, a central appetite regulating hormone, is also abundantly
released from the stomach. Whether apelin modulates gastric vagal afferent
signalling is unknown. We aimed to determine whether apelin modulates gastric
vagal afferent signalling under different states of nutrition. Female C57BL/6
mice were fed either a standard laboratory diet (SLD) or a high fat diet (HFD)
for 12 weeks. An in vitro gastric vagal afferent preparation was used to
determine the effect of apelin on gastric vagal afferent mechanosensitivity in
SLD mice, fed ad libitum or fasted overnight, and HFD mice. To determine the
signalling pathway of apelin via gastric vagal afferents, we determined the
expression of apelin receptor (APJ receptor) in the gastric mucosa, the whole
nodose ganglion and in gastric vagal afferent neurons innervating the stomach
using retrograde tracing and real-time quantitative reverse-transcription
polymerase chain reaction (qRT-PCR). The location of apelin and APJ receptor
within the gastric mucosa was determined by immunohistochemistry. Expression of
apelin and APJ receptor mRNA in gastric mucosa was determined using qRT-PCR.
Apelin inhibited the response of gastric mucosal vagal afferents to mucosal
stroking in fasted SLD mice, but not in mice fed ad libitum a SLD or HFD. Apelin
inhibited the response of gastric tension sensitive afferents to circular stretch
in SLD mice fed ad libitum or fasted, an effect not observed in HFD mice. APJ
receptor mRNA was detected in the gastric mucosa and whole nodose ganglion, but
not specifically in gastric vagal afferents neurons. In the gastric mucosa, APJ
receptor immunoreactive cells were co-localised or closely associated with apelin
containing cells and co-localised with serotonin, gastrin, histamine and gastric
intrinsic factor containing cells. In conclusion, apelin modulates gastric vagal
afferent signalling in a nutritional status dependent manner. Further, apelin
modulates gastric vagal afferents through an indirect pathway, possibly through
the release of hormones/peptides from the gastric mucosa.
PMID- 29964069
TI - The psychophysiology of stress and adaptation: Models, pathways, and
implications.
PMID- 29964070
TI - Oxytocin for learning calm and safety.
AB - The appropriate discrimination between safe and dangerous situations and the
subsequent decrease of fear expression in the presence of safety signals are
crucial for survival and mental health. Learning of safety associations is often
studied in terms of fear extinction, that is re-learning of a previously
conditioned stimulus which is now no longer positively associated with danger.
Numerous studies investigated neurobiological processes of fear extinction and
provide a valid picture of the underlying neural structures and endocrine
processes involved. However, a formerly neutral conditioned stimulus (CS) can
also predict the non-occurrence of an aversive, potentially dangerous,
unconditioned stimulus (US) from the very beginning and thus can serve as a
safety stimulus. This process has been termed safety learning. Although safety
learning has been known for almost a century, there has been little research on
its underlying neurobiological mechanisms, in contrast to the more prominent
Pavlovian fear conditioning and fear extinction. In this review, we propose that
the well-known action of the hypothalamic neuropeptide oxytocin (OXT) in the
regulation of fear and stress responses is complementary to safety learning. We
summarize the literature focused on OXT signaling and safety learning in animals
and humans, from the first studies of fear extinction and conditioned inhibition
of fear to the most recent findings in molecular and behavioral research on
initial social safety stimuli. At the end, we discuss the application of OXT as a
therapeutic agent to psychopathologies related to deficits in safety learning.
PMID- 29964071
TI - Agmatine attenuates depressive-like behavior and hippocampal oxidative stress
following amyloid beta (Abeta1-40) administration in mice.
AB - Depression is one of the most common psychiatric symptoms in Alzheimer's disease
(AD), and several studies have shown that oxidative stress plays a key role in
the etiopathology of both AD and depression. Clinical studies indicate reduced
efficacy of the current antidepressants for the treatment of depression in AD. In
this regard, agmatine emerges as a neuroprotective agent that presents diverse
effects, including antidepressant and antioxidant properties. Here we
investigated the antioxidant and antidepressant-like effects of agmatine in a
mouse model of AD induced by a single intracerebroventricular (i.c.v.)
administration of amyloid-beta 1-40 (Abeta). Mice were treated with agmatine (10
mg/kg, intraperitoneally) once a day during seven consecutive days. The first
administration of agmatine was 24 h before the i.c.v. injection of aggregated
Abeta 1-40 (400 pmol/mouse). Ten days after Abeta injection, mice were evaluated
in the forced swimming test (FST) and open field test for assessment of
depressive-like behavior and locomotor activity, respectively. Oxidative
parameters were evaluated in the hippocampus of mice 24 h after Abeta injection.
Agmatine prevented Abeta-induced increase in hippocampal lipid peroxidation
levels and Abeta-induced decrease in catalase activity. In addition, agmatine
prevented the increase in immobility time in the FST and the decrease in the
latency to the first immobility episode induced by Abeta, without changing
locomotion in the open field test. These results demonstrate the antioxidant and
antidepressant-like effects of agmatine in a mouse model of AD, indicating the
potential of agmatine for the treatment of depression associated to AD.
PMID- 29964072
TI - Causal and functional interpretation of mu- and delta-opioid receptor profiles in
mesoaccumbens and nigrostriatal pathways of an oral stereotypy phenotype.
AB - Spontaneous stereotypic behaviours are repetitive, compulsive, topographically
invariant response patterns commonly observed in captive or domestic animals,
which have been linked to dysfunction of basal ganglia input/output pathways.
There is evidence that endogenous opioids play a key regulatory role in basal
ganglia direct and indirect pathways, but their precise role, both causally and
functionally, in spontaneous stereotypic behaviour is unclear. Here we examined
the profile of mu- and delta-opioid receptors (density [Bmax] and affinity [Kd])
of basal ganglia structures in stereotypy (n = 10) and non-stereotypy (n = 10)
animals using a competitive ligand binding approach. Mu receptor densities were
significantly higher in the nucleus accumbens (p < 0.001), ventral tegmentum area
(p < 0.001) and caudate nuclei (p < 0.001) of stereotypy compared to control
animals. No differences were observed for delta Bmax values in any of the brain
regions studied (p > 0.15). Receptor binding affinity was only found to be
significantly different between control and stereotypy animals for mu receptors
on the caudate region; (p < 0.001). Our findings suggest that increased
inhibition (via mu-opioid receptors) of the indirect (dorsal striatopallidal)
pathways are associated with spontaneous stereotypy development. Data also
suggested that different types of spontaneous stereotypies (e.g. oral versus
locomotor) within or a cross species may have a different neurological basis.
This may have important implications for understanding the aetiology and function
of these behaviours. In some instances (oral stereotypy), the behaviour may be
associated with allostasis, a process that could enhance the reward value of
appetitive behaviour performance (as a starting point of stereotypy development).
PMID- 29964073
TI - Detection of root-infecting fungi on cool-season turfgrasses using loop-mediated
isothermal amplification and recombinase polymerase amplification.
AB - Root-infecting fungal pathogens such as Gaeumannomyces avenae, Ophiosphaerella
korrae, and Magnaporthiopsis poae cause extensive damage to amenity turfgrasses
in temperate climates. The diseases they cause are difficult to diagnose by
visual symptoms or microscopic inspection, and traditional polymerase chain
reaction-based assays require large financial investments in equipment such as
thermal cyclers and highly trained staff. The primary objective of this research
was to develop fast and accurate detection assays for the three pathogens listed
above that did not require the use of thermal cycling equipment. Loop-mediated
isothermal amplification (LAMP) and recombinase polymerase amplification (RPA)
assays were developed for each pathogen based on known fungal cultures. The
assays were tested on 27 samples received at the University of Wisconsin's
Turfgrass Diagnostic Laboratory in 2016 and 2017 and both methods provided
accurate diagnoses within about 30 min with minimal sample preparation. However,
the RPA assays had lower levels of false positive contamination relative to the
LAMP assays and are more likely to be effective in a field or diagnostic
laboratory for improved turf root-pathogen detection.
PMID- 29964074
TI - Nrg1 deficiency modulates the behavioural effects of prenatal stress in mice.
AB - Little is known about the exact genes that confer vulnerability or resilience to
environmental stressors during early neurodevelopment. Partial genetic deletion
of neuregulin 1 (Nrg1) moderates the neurobehavioural effects of stressors
applied in adolescence and adulthood, however, no study has yet examined its
impact on prenatal stress. Here we examined whether Nrg1 deficiency in mice
modulated the impact of prenatal stress on various behaviours in adulthood. Male
heterozygous Nrg1 mice were mated with wild-type female mice who then underwent
daily restraint stress from days 13 to 19 of gestation. Surprisingly, prenatal
stress had overall beneficial effects by facilitating sensorimotor gating,
increasing sociability, decreasing depressive-like behaviour, and improving
spatial memory in adulthood. Such benefits were not due to any increase in
maternal care, as prenatal stress decreased nurturing of the offspring. Nrg1
deficiency negated the beneficial behavioural effects of prenatal stress on all
measures except sociability. However, Nrg1 deficiency interacted with prenatal
stress to trigger locomotor hyperactivity. Nrg1 deficiency, prenatal stress or
their combination failed to alter acute stress-induced plasma corticosterone
concentrations. Collectively these results demonstrate that Nrg1 deficiency
moderates the effects of prenatal stress on adult behaviour, but it does so in a
complex, domain-specific fashion.
PMID- 29964075
TI - RESP18 deficiency has protective effects in dopaminergic neurons in an MPTP mouse
model of Parkinson's disease.
AB - Regulated endocrine-specific protein, 18 kDa (RESP18) was first cloned in 1994.
Its function in the brain especially in neurodegenerative diseases remains
unclear. In this study, RESP18 knockout (KO) and littermate wild-type (WT) mice
were comprehensively analyzed. The dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine (MPTP) was applied to generate subchronic Parkinson's disease
model. We found that KO mice displayed a reduction in locomotor activity and
motor coordination under physiological conditions. Five and six days after MPTP
administration, the behavioral impairments were detected in MPTP-treated WT mice,
whereas such impairments were not detected in MPTP-treated KO mice. The depletion
of tyrosine hydroxylase-positive nerve fibers in the striatum was similar between
MPTP-treated KO mice and WT littermates. Furthermore, the striatal level of alpha
synuclein protein was increased by treatment with MPTP in WT mice, but not in KO
mice. The loss of dopaminergic neurons was markedly alleviated, and the
activation of glial cells was inhibited in the substantia nigra of KO mice
challenged with MPTP. These results suggested that RESP18 deficiency might
protect dopaminergic neurons against MPTP toxicity.
PMID- 29964076
TI - Multi-laboratory comparison of three commercially available Zika IgM enzyme
linked immunosorbent assays.
PMID- 29964078
TI - Brain mechanisms of visual long-term memory retrieval in primates.
AB - Memorizing events or objects and retrieving them from memory are essential for
daily life. Historically, memory processing was studied in neuropsychology, in
which patients provided us with insights into the brain mechanisms underlying
memory. Psychological hypotheses about memory processing have been further
investigated using neuroscience techniques, such as functional imaging and
electrophysiology. In this article, I briefly summarize recent findings on multi
scale neural circuitry for memory at the scale of single neurons and cortical
layers as well as inter-area and whole-brain interactions. The key idea which
connects multi-scale neural circuits is how neuronal assemblies utilize the
frequency of communication between neurons, cortical layers, and brain areas.
Using findings and ideas from other cognitive function studies, I discuss the
plausible communication between neurons involved in memory.
PMID- 29964077
TI - An improved reverse transcription loop-mediated isothermal amplification assay
for sensitive and specific detection of serotype O foot-and-mouth disease virus.
AB - A sensitive and specific swarm primer-based reverse transcription loop-mediated
isothermal amplification (sRT-LAMP) assay for the detection of serotype O foot
and-mouth disease virus (FMDV) was developed and evaluated. The assay
specifically amplified the VP3 gene of serotype O FMDV, but did not amplify the
VP3 gene of other serotype FMDVs or any other viruses. The limit of detection of
the assay was 102 TCID50/mL or 103 RNA copies/MUL, which is 100 times lower than
that of the RT-LAMP assay without swarm primers. The new assay is 10 times more
sensitive than reverse transcription-polymerase chain reaction (RT-PCR) and is
comparable to the sensitivity of real time RT-PCR (qRT-PCR). Evaluation of the
assay using different serotypes of FMDV strains showed 100% agreement with the RT
PCR results. The previously reported serotype O FMDV-specific RT-LAMP assay did
not detect 20 out of 22 strains of serotype O FMDVs, probably due to multiple
mismatches between the primer and template sequences, showing that it is not
suitable for detecting the serotype O FMDVs circulating in Pool 1 region
countries, including Korea. In contrast, the developed sRT-LAMP assay with
improved primers can rapidly and accurately diagnose serotype O FMDVs circulating
in Pool 1 region countries and will be a useful alternative to RT-PCR and qRT
PCR.
PMID- 29964079
TI - Current state of in vivo panning technologies: Designing specificity and affinity
into the future of drug targeting.
AB - Targeting ligands are used in drug delivery to improve drug distribution to
desired cells or tissues and to facilitate cellular entry. In vivo biopanning,
whereby billions of potential ligand sequences are screened in biologically
relevant and complex conditions, is a powerful method for identification of novel
target ligands. This tool has impacted drug delivery technologies and expanded
our arsenal of therapeutics and diagnostics. Within this review we will discuss
current in vivo panning technologies and ways that these technologies can be
improved to advance next-generation drug delivery strategies.
PMID- 29964080
TI - Zero-dimensional, one-dimensional, two-dimensional and three-dimensional
biomaterials for cell fate regulation.
AB - The interaction of biological cells with artificial biomaterials is one of the
most important issues in tissue engineering and regenerative medicine. The
interaction is strongly governed by physical and chemical properties of the
materials and displayed with differentiated cellular behaviors, including cell
self-renewal, differentiation, reprogramming, dedifferentiation, or
transdifferentiation as a result. A number of engineered biomaterials with micro-
or nano-structures have been developed to mimic structural components of cell
niche and specific function of extra cellular matrix (ECM) over past two decades.
In this review article, we briefly introduce the fabrication of biomaterials and
their classification into zero-dimensional (0D), one-dimensional (1D), two
dimensional (2D) and three-dimensional (3D) ones. More importantly, the influence
of different biomaterials on inducing cell self-renewal, differentiation,
reprogramming, dedifferentiation, and transdifferentiation was discussed based on
the progress at 0D, 1D, 2D and 3D levels, following which the current research
limitations and research perspectives were provided.
PMID- 29964082
TI - Long-term evaluation and feasibility study of the insulated screw electrode for
ECoG recording.
AB - BACKGROUND: A screw-shaped electrode can offer a compromise between signal
quality and invasiveness. However, the standard screw electrode can be vulnerable
to electrical noise while directly contact with the skull or skin, and the
feasibility and stability for chronic implantation in primate have not been fully
evaluated. NEW METHOD: We designed a novel screw electrocorticogram (ECoG)
electrode composed of three parts: recording electrode, insulator, and nut. The
recording electrode was made of titanium with high biocompatibility and high
electrical conductivity. Zirconia is used for insulator and nut to prevent
electrical noise. RESULT: In computer simulations, the screw ECoG with insulator
showed a significantly higher performance in signal acquisition compared to the
condition without insulator. In a non-human primate, using screw ECoG, clear
visual-evoked potential (VEP) waveforms were obtained, VEP components were
reliably maintained, and the electrode's impedance was stable during the whole
evaluation period. Moreover, it showed higher SNR and wider frequency band
compared to the electroencephalogram (EEG). We also observed the screw ECoG has a
higher sensitivity that captures different responses on various stimuli than the
EEG. COMPARISON: The screw ECoG showed reliable electrical characteristic and
biocompatibility for three months, that shows great promise for chronic implants.
These results contrasted with previous reports that general screw electrode was
only applicable for acute applications. CONCLUSION: The suggested electrode can
offer whole-brain monitoring with high signal quality and minimal invasiveness.
The screw ECoG can be used to provide more in-depth understanding, not only
relationship between functional networks and cognitive behavior, but also
pathomechanisms in brain diseases.
PMID- 29964081
TI - Matlab software for impedance spectroscopy designed for neuroscience
applications.
AB - BACKGROUND: Metal electrodes are a mainstay of neuroscience. Characterization of
the electrical impedance properties of these cuffs is important to ensure
successful and repeatable fabrication, achieve a target impedance, revise novel
designs, and quantify the success or failure of implantation and any potential
subsequent damage or encapsulation by scar tissue. NEW METHODS: Impedances are
frequently characterized using lumped-parameter circuit models of the electrode
electrolyte interface. Open-source tools to gather and analyze these frequency
sweep data are lacking. Here, we present such software, in the form of Matlab
code, which includes a GUI. It automatically acquires frequency sweep data and
subsequently fits a simplified Randles model to these data, over a user specified
frequency range, providing the user with the model parameter estimates. Also, it
can measure an unknown impedance of an element over a range of frequencies, as
long as an external resistor can be added for the measurements. RESULTS: The tool
was tested on five bright platinum nerve cuffs in vitro. The average charge
transfer resistance, solution resistance, CPE value, and impedance magnitude were
estimated. COMPARISON TO EXISTING METHODS: The measured values of the impedance
of cuffs were in agreement with the literature (Wei and Grill, 2009). Variation
between cuffs fabricated as consistently as possible amounted to 10% for
impedance magnitude and 4 degrees for impedance phase. CONCLUSION: The results
show that this low-cost tool can be used to characterize a cuff across different
conditions including after implantation. The latter makes it useful for a longer
term study of electrode viability.
PMID- 29964083
TI - In vitro and in vivo genotoxicity assessment of gold nanoparticles of different
sizes by comet and SMART assays.
AB - Due to the increasing use of gold nanoparticles (AuNPs) in different areas such
as medicine, biotechnology or food sector, human exposure to them has grown
significantly and its toxicity evaluation has become essential. Therefore, the
purpose of this study was to compare the potential genotoxic effects of 30, 50
and 90 nm AuNPs, using in vitro comet assay with the in vivo mutagenic and
recombinogenic activity (SMART Test) in Drosophila. The results indicated that in
both cell lines, 30, 50 and 90 nm (1-10 MUg ml-1) AuNPs increased DNA strand
breaks following 24 h treatment. This damage was not dose and size-dependent.
Moreover, a modified comet assay using endonuclease III and formamidopyrimidine
DNA glycosylase restriction enzymes showed that in both cell lines, pyrimidines
and purines were oxidatively damaged by all AuNPs, being 90 nm AuNPs slightly
more genotoxic. However, the data obtained with SMART showed that 30 nm AuNPs did
not modify the spontaneous frequencies of spots indicating lack of mutagenic and
recombinogenic activity. Therefore, further experiments must be carried out to
gain a better understanding of the mechanism of action of AuNPs to ensure their
safe use.
PMID- 29964084
TI - Protective effects of hydroxytyrosol against alpha-synuclein toxicity on PC12
cells and fibril formation.
PMID- 29964085
TI - Comparative effect of melatonin and quercetin in counteracting LPS induced
oxidative stress in bone marrow mononuclear cells and spleen of Funambulus
pennanti.
AB - A majority of cellular diseases, independent of their origin, are characterized
by a dramatic increase in Reactive Oxygen Species (ROS) in response to stress. In
most cases, the uncontrolled detrimental ROS outburst is difficult to handle for
the cellular machinery and eventually leads to cell mortality. In this study, we
compare the antioxidant efficacy of quercetin and melatonin to find out a better
alternative against lipopolysaccharide (LPS) induced tissue injury by oxidative
stress in Funambulus pennanti. Transient exposure to LPS significantly increased
ROS generation and lipid peroxidation levels in bone marrow mononuclear cells
(MNCs) and spleen which was further corroborated by decreased activities of SOD,
CAT and Gpx enzymes. It also downregulate the expression of cellular oxidative
stress response proteins Nrf-2 and HO-1 in spleen and decreases the proliferation
of bone marrow derived Granulocyte macrophage-colony forming unit cells (GM-CFU).
Both melatonin and quercetin pre-treatments rescued these effects, however, our
results indicated that the efficacy of melatonin to overcome oxidative stress was
significantly better than quercetin. Our findings support the idea that melatonin
is a better antioxidant and immunomodulator as compared to other alternatives and
perhaps may be employed in the development of effective therapeutics against ROS
dominated diseases.
PMID- 29964086
TI - From the Ca2+-activated F1FO-ATPase to the mitochondrial permeability transition
pore: an overview.
AB - Based on recent advances on the Ca2+-activated F1FO-ATPase features, a novel
multistep mechanism involving the mitochondrial F1FO complex in the formation and
opening of the still enigmatic mitochondrial permeability transition pore (MPTP),
is proposed. MPTP opening makes the inner mitochondrial membrane (IMM) permeable
to ions and solutes and, through cascade events, addresses cell fate to death.
Since MPTP forms when matrix Ca2+ concentration rises and ATP is hydrolyzed by
the F1FO-ATPase, conformational changes, triggered by Ca2+ insertion in F1, may
be transmitted to FO and locally modify the IMM curvature. These events would
cause F1FO-ATPase dimer dissociation and MPTP opening.
PMID- 29964087
TI - The hypothalamic neuropeptide orexin A- a possible regulator in glucose
homeostasis and germ cell kinetics in adult mice testes.
AB - Orexin A (OXA), a hypothalamic neuropeptide, regulates food intake, sleep-wake
cycle and energy balance by binding to its receptor (OX1R). Apart from brain, OXA
and OX1R are also present in peripheral organs including reproductive tissues.
Mammalian reproduction depends on uptake and proper utilization of glucose in the
testes. This study, therefore, examined role of OXA/OX1R system in regulation of
glucose homeostasis in adult mouse testis under in vivo and ex vivo conditions.
Binding of OXA to OX1R was blocked using an OX1R antagonist, SB-334867. Mice were
given a single bilateral intratesticular injection of the antagonist at doses of
4 and 12MUg/mouse and sacrificed 24 h post-injection. In order to understand the
direct role of OXA in testes of adult mice, an ex vivo experiment was performed
where binding of OXA to OX1R in the testis was blocked by using the same OX1R
antagonist. The antagonist treatment affected testicular glucose and lactate
concentration with concomitant down-regulation in the expression of glucose
transporters 3 and 8. A decreased activity in lactate dehydrogenase enzyme and
imbalance between germ cell survival and proliferation were also noted in testes
in treated mice. The results of ex vivo study supported the results obtained from
in vivo study. The findings thus suggest involvement of OXA/OX1R system in
regulation of testicular glucose homeostasis and germ cell kinetics in adult
mice.
PMID- 29964088
TI - Mitophagy is activated in brain damage induced by cerebral ischemia and
reperfusion via the PINK1/Parkin/p62 signalling pathway.
AB - This study examined the course of mitophagy following cerebral ischemia with
reperfusion and the role of the PTEN-induced kinase 1 (PINK1)/Parkin/p62
signalling pathway. The middle cerebral artery of male Sprague-Dawley rats was
occluded for 90 min and was followed by different time-points of reperfusion.
Cerebral infarct areas were detected by 2,3,5-triphenyl tetrazolium chloride
staining, while brain damage was observed by haematoxylin and eosin staining.
Levels of LC3, Beclin1 and LAMP-1 were estimated by western blots. LC3B location
was observed in various cells in the neurovascular unit. In addition, PINK1
accumulation in damaged mitochondria and Parkin/p62 mitochondrial translocation
were investigated by double immunofluorescence staining. Finally, the levels of
PINK1, Parkin and p62 expression in mitochondrial fractions were estimated by
western blots. Cerebral ischemia with different time-points of reperfusion
resulted in infarct in the territory of the middle cerebral artery accompanied by
overall brain damage. In addition, we found up-regulation of LC3B, Beclin1, and
LAMP-1, as well as mitophagy activation after reperfusion, with peak expression
of these proteins at 24 h after reperfusion. Electron microscopy and
immunofluorescence indicated that LC3B was primarily located in neurons, although
lower levels of expression were found in astrocytes and even less in vascular
endothelial cells. Moreover, significant increases in PINK1 accumulation in the
outer membrane of mitochondria and increased Parkin/p62 mitochondrial
translocation were shown at 24 h after reperfusion. These findings suggest that
the PINK1/Parkin/p62 signalling pathway was involved in the pathophysiological
processes following ischemia and reperfusion.
PMID- 29964090
TI - Killer cell immunoglobulin-like receptor genotypes in a Chilean population from
Talca.
AB - Ninety healthy and unrelated volunteers were randomly selected to study the gene
frequencies of Killer-cell immunoglobulin-like receptors (KIRs) in a Chilean
(Talca) population. KIR typing was resolved by PCR-single specific primer (SSP),
and their gene frequencies were calculated by direct counting of the number of
positive and negative loci. The KIR genotype data is publicly available in the
Allele Frequencies Net Database under the name "Chile Talca KIR".
PMID- 29964089
TI - Marking of definitive HSC precursors in E7.5-E8.5 embryos using an Abcg2-CreER
lineage-tracing mouse model.
AB - Abcg2, a member of the ATP-binding cassette transporter family, is expressed in
adult hematopoietic stem cells (HSCs) and is required for the side population
phenotype of adult bone marrow HSCs and other adult tissue-specific stem cells.
Lineage tracing in adult mice using the Abcg2-Cre mouse model showed that Abcg2
marks HSCs, intestinal stem cells, and spermatogonial stem cells. It is unclear
whether definitive HSCs or their precursors in early embryonic development can be
marked by Abcg2 expression. Here, we treated pregnant Abcg2 Cre/Cre RosaLSL-YFP
mice with a single injection of 4-hydroxytamoxifen at embryonic day 7.5. Four
months after birth, a small yellow fluorescent protein-positive (YFP+) cell
population could be detected in all of the major white blood cell lineages and
this was stable for 8 months. Transplant of bone marrow cells or Sca1+YFP+ cells
from these mice showed continued multilineage marking in recipient mice at 4
months. These results demonstrate that Abcg2 expression marks precursors to adult
long-term repopulating HSCs at E7.5 to E8.5 and contributes to a stable
subpopulation of HSCs well into adulthood.
PMID- 29964091
TI - Bisphenol A modulates inflammation and proliferation pathway in human endometrial
stromal cells by inducing oxidative stress.
AB - Bisphenol A (BPA) has been implicated in altered human reproductive function. The
oxidative stress or change of inflammatory signaling may appear a key factor in
the biological changes of the human endometrium. Using MTT assay we assessed BPA
mediated modulation of oxidative stress and inflammation responses in human
endometrial stromal cells (ESCs). According to the results, reactive oxygen
species (ROS) generation was highest upon exposure to 1000 pmol BPA. Increased
mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB)
were demonstrated. Gene expression and release of inflammatory cytokines were
increased. Upon BPA exposure, elevated estrogen receptor (ER)-alpha expression
levels in ESCs correlated with changes in oxidative stress, inflammatory gene
expression and signal changes in cellular proliferation signaling. These findings
support that BPA induces oxidative stress and activates inflammatory signals in
cultured ESCs via ER-alpha. Together, this result may provide insight into the
association between BPA exposure and endometrium-related disorders.
PMID- 29964092
TI - Cocaine-induced epigenetic DNA modification in mouse addiction-specific and non
specific tissues.
AB - Cocaine-related DNA methylation studies have primarily focused on the specific
brain regions associated with drug addiction (e.g., the nucleus accumbens, NAc).
To date, no studies have focused on the complex role of both DNA methylation and
demethylation in the mechanisms of psychostimulant-induced addiction in the brain
and peripheral tissues. Therefore, in this study, we evaluated cocaine treatment
and withdrawal (animals were withdrawn from seven days of repeated injections of
cocaine that caused behavioral sensitization) effects on epigenetic DNA modifiers
(i.e., DNA methyltransferases, [DNMTs] and ten-eleven translocation enzymes
[TETs]) in an addiction-specific brain region (NAc), a structure outside the
mesolimbic dopaminergic system (cerebellum, Cer), and in peripheral blood cells
(PBCs). Using a mouse behavioral sensitization model, we demonstrated that acute
cocaine (AC; 0.5 h) treatment significantly decreased Dnmt1, Dnmt3a, Tet1, and
Tet2 mRNA levels in the NAc and PBC, whereas at 24 h after AC treatment, Dnmt
mRNA expression and enzyme activity levels were significantly increased. Acute
procaine treatment caused the opposite effect on the Dnmt3a mRNA level in PBCs;
this outcome suggests that the inhibition of voltage-gated sodium channels may be
the mechanism that alters Dnmt expression in PBCs. Cocaine withdrawal is
associated with increased expression of Dnmts in the NAc, Cer and PBCs and the
decreased expression of Tet1 and Tet3 in the NAc. Additionally, cocaine
withdrawal increased DNMT but decreased TET activity levels, and these changes
were associated with enhanced global and selected candidate gene promoter-region
DNA methylation and hydroxymethylation levels in the NAc and PBCs. Together,
these data indicate that cocaine treatment and withdrawal affect the expression
of epigenetic DNA modifiers in both addiction-specific brain structures and
structures outside of the mesolimbic dopaminergic system and PBCs.
PMID- 29964094
TI - Positive psychology in the investigation of psychedelics and entactogens: A
critical review.
AB - RATIONALE: We reviewed the concepts and empirical findings in studies with
psychedelics and entactogens related to positive psychology - the study of
healthy human functioning, well-being and eudaemonia. It is an unresolved
question how beneficial effects of psychedelics and entactogens are related to
the potential risks of these substances - particularly in non-clinical settings.
METHODS: We searched in PubMed, PsychINFO and the Cochrane Library for controlled
clinical and epidemiological studies which applied concepts from positive
psychology. We included N = 77 eligible studies with 9876 participants published
before November 1st, 2017: (1) quantitative studies (N = 54), (2) preliminary or
exploratory studies and reviews not including meta-analyses (N = 17), and (3)
studies evidencing primarily negative results (N = 6). RESULTS: Positive
psychology concepts have been applied for measuring effects of clinical trials,
recreational and ceremonial use of psychedelics and entactogens. Psychedelics and
entactogens were shown to produce acute and long-term effects on mood, well
being, prosocial behaviours, empathy, cognitive flexibility, creativity,
personality factors like openness, value orientations, nature-relatedness,
spirituality, self-transcendence and mindfulness-related capabilities.
CONCLUSIONS: There is preliminary evidence for beneficial effects of psychedelics
and entactogens on measures of positive psychology in clinical and healthy
populations, however their sustainability remains largely unresolved. The
reported results must be considered preliminary due to methodological
restrictions. Since longitudinal data on both positive and adverse effects of
psychedelics are lacking, more rigorous and standardized measures from positive
psychology should be applied in less biased populations with prospective
longitudinal designs to carefully assess the benefit-risk-ratio. This article is
part of the Special Issue entitled 'Psychedelics: New Doors, Altered
Perceptions'.
PMID- 29964093
TI - Exposure to environmental enrichment attenuates addiction-like behavior and
alters molecular effects of heroin self-administration in rats.
AB - Environmental factors profoundly affect the addictive potential of drugs of abuse
and may also modulate the neuro-anatomical/neuro-chemical impacts of uncontrolled
drug use and relapse propensity. This study examined the impact of environmental
enrichment on heroin self-administration, addiction-related behaviors, and
molecular processes proposed to underlie these behaviors. Male Sprague-Dawley
rats in standard and enriched housing conditions intravenously self-administered
similar amounts of heroin over 14 days. However, environmental enrichment
attenuated progressive ratio, extinction, and reinstatement session responding
after 14 days of enforced abstinence. Molecular mechanisms, namely DNA
methylation and gene expression, are proposed to underlie abstinence-persistent
behaviors. A global reduction in methylation is reported to coincide with
addiction, but no differences in total genomic methylation or repeat element
methylation were observed in CpG or non-CpG (CH) contexts across the mesolimbic
circuitry as assessed by multiple methods including whole genome bisulfite
sequencing. Immediate early gene expression associated with drug seeking, taking,
and abstinence also were examined. EGR1 and EGR2 were suppressed in mesolimbic
regions with heroin-taking and environmental enrichment. Site-specific
methylation analysis of EGR1 and EGR2 promoter regions using bisulfite amplicon
sequencing (BSAS) revealed hypo-methylation in the EGR2 promoter region and EGR1
intragenic CpG sites with heroin-taking and environmental enrichment that was
associated with decreased mRNA expression. Taken together, these findings
illuminate the impact of drug taking and environment on the epigenome in a locus
and gene-specific manner and highlight the need for positive, alternative rewards
in the treatment and prevention of drug addiction.
PMID- 29964095
TI - Group I metabotropic glutamate receptors generate two types of intrinsic membrane
oscillations in hippocampal oriens/alveus interneurons.
AB - GABAergic interneurons in the hippocampus are critically involved in almost all
hippocampal circuit functions including coordinated network activity.
Somatostatin-expressing oriens-lacunosum moleculare (O-LM) interneurons are a
major subtype of dendritically projecting interneurons in hippocampal subregions
(e.g., CA1), and express group I metabotropic glutamate receptors (mGluRs),
specifically mGluR1 and mGluR5. Group I mGluRs are thought to regulate
hippocampal circuit functions partially through GABAergic interneurons. Previous
studies suggest that a group I/II mGluR agonist produces slow supra-threshold
membrane oscillations (<0.1 Hz), which are associated with high-frequency action
potential (AP) discharges in O-LM interneurons. However, the properties and
underlying mechanisms of these slow oscillations remain largely unknown. We
performed whole-cell patch-clamp recordings from mouse interneurons in the
stratum oriens/alveus (O/A interneurons) including CA1 O-LM interneurons. Our
study revealed that the selective mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine
(DHPG) induced slow membrane oscillations (<0.1 Hz), which were associated with
gamma frequency APs followed by AP-free perithreshold gamma oscillations. The
selective mGluR1 antagonist (S)-(+)-alpha-Amino-4-carboxy-2-methylbenzeneacetic
acid (LY367385) reduced the slow oscillations, and the selective mGluR5
antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) partially
blocked them. Blockade of nonselective cation-conducting transient receptor
potential channels, L-type Ca2+ channels, or ryanodine receptors all abolished
the slow oscillations, suggesting the involvement of multiple mechanisms. Our
findings suggest that group I mGluR activation in O/A interneurons may play an
important role in coordinated network activity, and O/A interneuron vulnerability
to excitotoxicity, in disease states like seizures, is at least in part due to an
excessive rise in intracellular Ca2+.
PMID- 29964097
TI - Long noncoding RNA TMEM75 promotes colorectal cancer progression by activation of
SIM2.
AB - Colorectal cancer (CRC) is one of the most frequent cancers worldwide and leads
to a great many deaths each year. However, the underlying mechanisms that
regulate colorectal cancer development and progression remain elusive. Here we
identified an uncharacteristic long noncoding RNA TMEM75 that was upregulated in
colorectal cancer compared to non-tumor tissues. We found that TMEM75 expression
levels are positively correlated with advanced clinical stage. TMEM75
significantly inhibited the proliferation, migration, and invasion of CaCo2 and
HCT116 cells in vitro. Moreover, TMEM75 silence delayed tumor growth in vivo.
Mechanistically, TMEM75 was demonstrated to initiate the expression of
transcription factor SIM2. We also found that the expression of SIM2 was
upregulated and positively correlated that of TMEM75 in colorectal cancer
tissues. Furthermore, ectopic expression of SIM2 rescued TMEM75 depletion-induced
inhibition on cell proliferation, migration and invasion in colorectal cancer.
Altogether, our findings indicated that TMEM75 functions as an oncogene relying
on activation of SIM2 in colorectal cancer for the first time.
PMID- 29964096
TI - A novel missense mutation of CRYGS underlies congenital cataract in a Chinese
family.
AB - Congenital cataract is a clinically and genetically heterogeneous disease. In
this study, we examined a five-generation Chinese family with autosomal dominant
nuclear congenital cataracts by whole exome sequencing. A novel heterozygous
missense mutation c.199T>A, p.(Tyr67Asn) in CRYGS was identified in this family.
The p.(Tyr67Asn) substitution was predicted to decrease the local hydrophobicity
and affect the three-dimensional structure of gammaS-crystallin, and resulted in
a portion of mutant protein translocation from the cytoplasm to cell membrane.
Our observations expand the mutation spectrum of CRYGS and provide further
evidence for the genetic basis and molecular mechanism of congenital cataract.
PMID- 29964098
TI - Dihydrotestosterone regulates expression of CD44 via miR-328-3p in triple
negative breast cancer cells.
AB - Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks
effective targeted therapeutics strategy and has poor prognosis. Targeting
androgen receptor (AR) in TNBC is thought to be a promising approach. We
hypothesized that AR, functioning as a transcription factor, controls cell
behavior via regulating the expression of microRNA molecules (miRNAs). The
expression of 84 breast cancer-specific miRNAs in MDA-MB-231 cells, a highly
invasive TNBC model system, was investigated using PCR arrays following treatment
of cells with 5alpha-dihydrotestosterone (DHT). The expression of 33 miRNAs was
changed by more than 2 folds including miR-328-3p, which was up-regulated by 13
folds. Transfection of cells with either miR-328-3p mimic or anti-sense molecules
decreased cell motility. DHT-mediated effect on the expression and function of
CD44, a target of miR-328-3p, was investigated. CD44 expression and cell adhesion
to hyaluronic acid (HA) were down-regulated when cells were treated with DHT or
transfection with a miR-328-3p mimic. On the other hand, the AR antagonist,
bicalutamide, or transfection of cells with miR-328-3p anti-sense molecules had
the opposite effect. Cells transfected with miR-328-3p anti-sense molecules
reduced the negative effect of DHT on CD44 expression and cell adhesion to HA. In
addition, DHT further reduced the expression of CD44 and cell adhesion to HA in
cells transfected with miR-328-3p mimic. These results strongly suggest that
miRNAs can mediate AR regulation of breast cancer cells and that AR controls the
expression of CD44 via miRNA-dependent and independent mechanisms.
PMID- 29964099
TI - Transfer of dry surface biofilm in the healthcare environment: the role of
healthcare workers' hands as vehicles.
AB - BACKGROUND: Dry surface biofilms (DSBs) persist for extended periods in hospital,
and may play a significant role in transmission of healthcare-associated
infections. AIM: To determine whether DSBs may be transferred from hospital
surfaces to healthcare workers' hands. METHOD: Twelve-day Staphylococcus aureus
DSB was grown on polycarbonate and glass coupons in a CDC Biofilm Reactor(r). A
total of 1.8 * 106 and 8.8 * 105 bacteria grew on the polycarbonate and glass
coupons respectively. Transmission was tested by lifting the coupon with
forefinger and thumb of ungloved hands to a height of 30 cm, then touching horse
blood agar (HBA) plates 19 sequential times. Transferred bacterial number was
determined by colony-forming units. The effect of DSB wetting on biofilm transfer
was tested with 5% neutral detergent treatment for 5 s. FINDINGS: Between 5.5 and
6.6% of the DSB bacteria were transferred to hands with one touch and ~20% were
then transferred to HBA with one touch, giving an overall transfer rate of 1.26%
and 1.04% for polycarbonate and glass coupons, respectively. Detergent treatment
had little effect on bacterial removal from coupons, but, for biofilm grown on
polycarbonate, significantly increased transferral to HBA (P < 0.001) to 5.2%.
Large numbers of bacteria were transferred by bare hands to multiple fomites. One
third of polycarbonate coupons transferred >1000 colonies during the first five
sequential touches. Sufficient bacteria to cause infection were transmitted up to
19 times following one touch of the DSB. CONCLUSION: DSB bacteria are transferred
by hands from one fomite to multiple fomites, suggesting that DSB may serve as a
persistent environmental source of pathogens.
PMID- 29964100
TI - Does screening neonates in the neonatal intensive care unit for Pseudomonas
aeruginosa colonization help prevent infection?
AB - BACKGROUND: Pseudomonas aeruginosa (PA) is a Gram-negative environmental organism
that can cause severe infection in immunosuppressed patients, including preterm
neonates. In recent years, it has become common practice to screen neonates for
PA colonization. AIM: To assess the value of screening neonates for PA in (1)
predicting the risk of developing severe PA infection and (2) directing infection
control practice. METHODS: Between August 2012 and September 2015, babies
admitted to the neonatal intensive care unit (NICU) at North Bristol NHS Trust
were screened routinely for PA colonization on admission and weekly thereafter.
Data were also collected on babies who developed PA infection. Environmental
samples from the NICU were tested for the presence of PA. Variable number tandem
repeat (VNTR) typing was performed on all strains of PA from babies and the
environment. FINDINGS: No babies with positive screens subsequently developed PA
infection. There was no VNTR strain evidence supporting cross-infection from the
environment or other babies. CONCLUSION: Screening neonates for PA did not
identify babies who subsequently developed PA infection. Following cessation of
screening in September 2015, there was no increase in the number of babies
identified with PA infection.
PMID- 29964101
TI - Surveying Retracted Studies and Notices Within the Field of Radiation Oncology.
AB - PURPOSE: The purpose of this study was to characterize retracted studies within
the field of radiation oncology. METHODS AND MATERIALS: Computerized searches
were performed in Ovid MEDLINE, PubMed, Ovid EMBASE, and the Cochrane Library up
to May 2017 looking for retracted studies using the terms "retraction note,"
"retracted note," "withdrawn" and "radiotherapy," and "radiation oncology."
Additional studies were identified by hand-searching 10 discipline-specific
journals. Two authors independently screened papers and then extracted author
demographics, journal characteristics, and retraction-specific variables.
RESULTS: Of the 58 studies identified, the most common reasons for retraction
were misconduct (43%), methodological error (21%), authorship issues (5%),
unknown causes (5%), and journal (administrative) errors (3%). A total of 13
systematic reviews or protocols (22%) were withdrawn from the Cochrane Library
for being out-of-date or redundant. All but one retracted study and retraction
notice were available in portable document format. Of the 57 retrieved papers,
79% were identified as retracted via in-text notations or watermarks. Overall
median time to retraction was 44 months (interquartile range, 11-98 months).
However, 42 studies (72%) were still cited after retraction notices were
published. CONCLUSIONS: A retracted study within the field of radiation oncology
remains a relatively uncommon event. Although promising, our data suggest that
the majority of these retracted articles continue to be cited as valid research.
As such, there is still a need for clinicians to remain vigilant with their
academic rigor and good clinical research practices. There is an urgent need for
publication houses to foster universal publishing standards along with discipline
specific retraction guidelines.
PMID- 29964102
TI - Chicory (Cichorium intybus L.) polysaccharides attenuate high-fat diet induced
non-alcoholic fatty liver disease via AMPK activation.
AB - Chicory polysaccharides (CP) from Cichorium intybus L. roots were extracted and
fractionated to isolate two novel polysaccharide fractions, CP-1 and CP-2. CP-1
is a heteropolysaccharide that is mainly composed of sorbin, glucose, fructose,
and glucitol at a molar ratio of 1.00:5.58:13.97:10.32. The molecular weight of
CP-1 was 8511.4 Da. The hepatoprotective effect of CP-1 was investigated in a rat
model of high-fat diet induced non-alcoholic fatty liver disease (NAFLD) rats.
Results indicated that the oral administration of CP-1 significantly decreased
body weight and liver index in NAFLD rats. CP-1 also significantly increased
serum levels of SOD and HDLC, and decreased the levels of ALT, AST, TG, TC, LDL
C, GLU, ALP, LDH, and MDA in NAFLD rats. Meanwhile, CP-1 effectively decreased
MDA, TC, and TG, and increased SOD and T-AOC in the livers of NAFLD rats.
Furthermore, CP-1 also increased the hepatic expression of p-AMPKalpha, ATGL, CPT
1, and p-ACC, and reduced the hepatic expression of ACC, FAS, and SCD-1.
Moreover, histopathological examination of the livers showed that CP-1
significantly ameliorated the symptoms of NAFLD rats. Therefore, CP-1
significantly attenuated the high-fat diet-induced NAFLD in rats via AMPK
activation.
PMID- 29964103
TI - Removal of Cd2+, Ni2+ and PO43- from aqueous solution by hydroxyapatite-bentonite
clay-nanocellulose composite.
AB - A novel hydroxyapatite-bentonite clay-nanocellulose (CHA-BENT-NCC) composite
material was successfully prepared as adsorbent for the removal of Ni2+, Cd2+ and
PO43- from aqueous solutions. Scanning electron microscopy (SEM), transmission
electron microscopy (TEM), energy dispersive analysis of X-rays (EDAX), X-ray
diffraction analysis (XRD) and Fourier-transform infrared spectroscopy (FTIR)
were used for characterization of the adsorbent. The effect of pH, contact time,
temperature, and initial adsorbate concentration were studied for optimization
purpose. The adsorption behavior of the investigated ions were well described by
the Freundlich adsorption model, and the maximum adsorption capacity for Ni2+,
Cd2+ and PO43- was estimated to be 29.46 mmol/g, 10.34 mmol/g and 4.90 mmol/g,
respectively. Desorption efficiency was achieved by treatment with 0.01 M HNO3
for metals and 0.10 M NaOH for PO43-. Five adsorption-desorption cycles were
performed without significant decrease in adsorption capacities. The CHA-BENT-NCC
material proved to be a very effective adsorption material for the treatment of
mining water also from a copper mine in Finland.
PMID- 29964104
TI - Extraction, characterization and antioxidant activities of pumpkin
polysaccharide.
AB - Extraction and antioxidant activities of polysaccharide from pumpkin were
discussed. The crude polysaccharide was extracted with the hot water. It showed
that the calcium chloride (CaCl2) method was ideal for deproteinization. The
pumpkin polysaccharide was linked by the alpha/beta-glycosidic bond, and it might
contain acetyl groups. Pumpkin polysaccharide was heteropolysaccharide composed
of six monosaccharides. In addition, it indicated that pumpkin polysaccharide
exhibited good antioxidant activities.
PMID- 29964105
TI - Antibacterial and antifungal effects of chitosan nanoparticles on tissue
conditioners of complete dentures.
AB - INTRODUCTION: One of the most serious problems in dentistry is the growth of
bacteria and fungi on complete dentures. The growth in question takes place on
the surface of the elastic liners of their tissue conditioners. However, this
problem can be solved by adding nanoparticles with antibacterial and antifungal
properties to the tissue conditioners. MATERIALS AND METHODS: After bacterial and
fungal microorganisms were cultured, the suspensions obtained were incubated for
24 and 48 h respectively. It was conducted under incubation conditions with a
tissue conditioner containing chitosan nanoparticles. The growth rate of
microorganisms was measured in the culture medium using a spectrophotometer.
RESULTS: Different concentrations of chitosan nanoparticles led to the inhibition
of fungal and bacterial growth in within both 24 and 48 h. CONCLUSION: Chitosan
nanoparticles have an inhibitory effect on the growth of bacteria and pathogenic
fungi.
PMID- 29964106
TI - Facile and cost-effective synthesis of glycogen-based conductive hydrogels with
extremely flexible, excellent self-healing and tunable mechanical properties.
AB - In materials science and engineering, the designing of hydrogels with excellent
self-healing and tunable mechanical properties is an inviting issue. In this
study, we introduce the sacrificial bonds interactions in a hybrid hydrogel of
natural and synthetic polymers, to give a hydrogel with autonomous self-healing
ability and tunable mechanical properties. Glycogen, a natural polymer tends to
strengthen the hydrogel while PVA, a synthetic polymer plays a critical role in
the flexibility and stretchability of the hydrogel. Hydrogels were designed by
the sacrificial non-covalent interactions with physical cross-linking of the
polymer chains to the trivalent metal ions. Functional groups of the polymers
interact with sacrificial hydrogen bonds with and with the metal ions, they
interact through sacrificial coordination interactions with different strength,
results tunable sacrificial bonds. Weaker sacrificial bonds rupture prior to the
strong sacrificial bonds upon external loading, which dissipate the energy and
endow the hydrogel with adjustable mechanical and self-healing properties. The
tunable mechanical properties and excellent self-healing efficiency enlarge the
application areas of the developed hydrogel in various fields.
PMID- 29964107
TI - Study on water proton distribution and flow status of starch during the hydration
process.
AB - The hydration process of starch significantly affects the quality of starch-based
food, especially for samples with medium to low water content. In this paper,
rice starch, as a representative of cereal starch, and potato starch were chosen
as the samples. The proton distributions and flow status of the hydrated rice
starch and potato starch with moisture contents of 20-90% and the causes of the
differences between them were investigated by 1H LF-NMR. The longitudinal and
transverse proton relaxation (T1 and T2) of the two starch systems was obtained
using the inversion recovery (IR) sequence, the free induction decay (FID)
sequence, and the multi-pulse echo CPMG sequence. Through the detection of
longitudinal relaxation, two different populations were found in the two hydrated
starch systems, and the changes were linearly related to the moisture content.
Through the detection of transverse relaxation, two populations were
distinguished in the hydrated rice starch samples with different moisture
content, whereas two to four different populations were detected in the hydrated
potato starch samples. Because of the differences in particle size and swelling
capacity, hydrated potato starch showed greater proton freedom and more
observable types of protons than hydrated rice starch.
PMID- 29964108
TI - Adsorption of rosmarinic acid from aqueous solution on chitosan powder.
AB - In present study the adsorption of rosmarinic acid (RA) on chitosan (CH) powder
from aqueous solution have been investigated in order to obtain insoluble RA-CH
complexes with high amount of RA. The pseudo-second kinetic model and the
Langmuir adsorption model described the kinetic and equilibrium adsorption of RA
on CH with high correlation coefficients. With the increase of adsorption
temperature the rate of adsorption decreased but amount of adsorbed RA increased.
It was established that adsorption of RA on CH occurred in two steps, and
relevant adsorption mechanism was proposed. The formation of RA-CH with the molar
ratio of RA to CH equal to 0.11, 0.22. 0.39, 0.6 and 0.8 was investigated by FT
IR and steady-state fluorescence spectroscopic techniques. By the increase of RA
amount in RA-CH complexes the character of both FT-IR and fluorescence spectra
changed. The antioxidant activity of RA-CH was investigated by ABTS method and
showed that RA-CH having higher amount of adsorbed RA has prolonged antioxidant
activity.
PMID- 29964109
TI - A facile approach to light weight, high porosity cellulose aerogels.
AB - This work reported a facile approach to make cellulose-based aerogels in
NaOH/urea aqueous solution via freeze-drying hydrogels, which were obtained by
mixing N,N'-methylene bisacrylamide (MBA) with cellulose solution at room
temperature. The cellulose solution showed pronounced MBA-induced gelation
behaviors. The obtained cellulose aerogels possessed a three dimensional network
with macroporous structure (20-600 MUm), low density (0.0820-0.0083 g/cm3), high
porosity (90.3%-99.02%), moderate thermal stability (275 degrees C) and certain
absorbency to Cu (II) (85 mg/g) and methylene blue (MB) (115 mg/g). Cellulose
aerogels with different morphologies can be obtained by adjusting the cross
linking degree and the concentration of cellulose. This kind of aerogel provides
an excellent matrix for the functionalization of cellulose-based aerogel.
PMID- 29964110
TI - Rheological, textural and emulsifying properties of an exopolysaccharide produced
by Mesorhizobium loti grown on a crude glycerol-based medium.
AB - In the present study, a new extracellular polysaccharide (EPS-M816) was obtained
during the growth of Mesorhizobium loti Semia 816 on a crude glycerol-based
medium. EPS-M816 precipitate mainly consisted of carbohydrates (82.54%) and
proteins (11.31%), and the weight average molecular weight was estimated at 1.646
* 106 Da. The biopolymer was characterized by FT-IR and NMR spectroscopy, and was
found to have typical functional groups of other rhizobial polysaccharides.
Furthermore, the rheological and emulsifying properties were investigated. The
EPS-M816 solution (1.0% w/v) showed typical pseudoplastic non-Newtonian fluid
behavior, and the addition of sodium and potassium chloride (1 mol L-1) increased
the apparent viscosity. Regarding its emulsification activity, EPS-M816 formed
emulsions with different food-grade vegetable oils (soybean, rice, canola,
sunflower and corn oils), showing emulsification index values over 65% in 24 h,
indicative of strong emulsion-stabilizing capacity. The biopolymer was able to
form gels with texture parameters similar to those reported for xanthan gum and
low syneresis. Overall, these results suggest that EPS-M816 is a good candidate
for application in the food, cosmetics and pharmaceutical industries as a
thickening, gelling, stabilizing and emulsifying agent.
PMID- 29964111
TI - Structural and functional alteration of human alphaA-crystallin after exposure to
full spectrum solar radiation and preventive role of lens antioxidants.
AB - The chronically exposure of eye lenses to ultra violet and visible light of the
solar radiation is an important risk factor for development of the senile
cataract diseases. Various photosensitizer molecules including riboflavin (RF)
play a significant role in photo-oxidative damages of lens proteins underlying
development of opacity in the lenticular tissues. In the current study, RF
mediated photo-oxidation of human alphaA-crystallin (alphaA-Cry) was assessed
using SDS-PAGE analysis, dynamic light scattering and other spectroscopic
assessments. The RF-photosensitized reactions led to non-disulfide covalent cross
linking, oligomerization and significant structural changes in alphaA-Cry. The
photo-damaging of alphaA-Cry under solar radiation was also accompanied by the
reduction in both Trp and Tyr fluorescence intensities which followed by the
formation of new photosensitizer chromophores. The solvent exposed hydrophobic
patches, secondary structures and chaperone-like activity of alphaA-Cry were
significantly altered after exposure to the solar radiation in the presence of
RF. Although glutathione and ascorbate were capable to partially protect the
photo-induced structural damages of human alphaA-Cry, they also disrupted its
chaperone function when co-exposed with this protein to the solar radiation.
Also, the most promising data were obtained with cysteine which its availability
in the lenticular tissues is a rate limiting factor for the biosynthesis of
glutathione. Overall our results suggest that glutathione and ascorbate, as the
major anti-oxidant compounds within lenticular tissues, demonstrate controversial
effect on structure and chaperone-like activity of human alphaA-Cry. Elucidation
of this effect may demand further experiments.
PMID- 29964112
TI - Physicochemical characterization, antioxidant and anti-proliferative activities
of a polysaccharide extracted from psyllium (P. ovata) leaves.
AB - Psyllium leaves polysaccharides were physicochemically characterized and
evaluated for antioxidant, free-radical scavenging and anticancer activities. The
polysaccharide comprised of arabinose, rhamnose, xylose, galactose, and glucose.
FTIR and NMR study exhibited the presence of key functional groups whereas
morphological study revealed that crude polysaccharides are aggregates of
irregular shape, non-porous, and smooth surface, while the purified products are
porous and fibrous in nature. Extracted polysaccharides were thermally stable and
exhibited the characteristic diffraction curve with a higher viscosity and size
distribution. Biochemical analyses demonstrated the higher antioxidant and
scavenging activities. In vitro anticancer assay showed the maximum inhibitory
effect about 33% on Huh7 and about 30% on HeLa cell lines. The study confirmed
the presence of high antioxidant and free-radical scavenging activities with a
potential anticancer activity. The polysaccharide could be developed as a
potential natural antioxidant and anticancer agents after comprehensive studies
on experimental animal models.
PMID- 29964113
TI - Extraction and characterization of an alginate from the Iranian brown seaweed
Nizimuddinia zanardini.
AB - Sodium alginate from Nizimuddinia zanardini (an Iranian brown algae) was
extracted with acid and alkaline solutions, partially and totally hydrolyzed and
analyzed for its biochemical composition. 1H NMR spectroscopy, SEC-MALLS, HPAEC
and FT-IR were performed to determine its structure and its physico-chemical
properties. This alginate has a M/G ratio of 1.1, a molecular weight of 103 kDa,
a polydispersity index of 1.22, and an intrinsic viscosity of 342 mL/g. Its
antioxidant activity was tested by DPPH radical scavenging showing its potential
for food preservation. Rheological properties of solutions of this alginate with
concentrations between 1 and 5% (w/v) in water and 0.5 M NaCl were investigated
indicating a Newtonian fluid type behaviour in water and a shear thinning fluid
type behaviour in NaCl solutions.
PMID- 29964114
TI - Porous electrospun starch rich polycaprolactone blend nanofibers for severe
hemorrhage.
AB - Starch nanofiber based hemostat was prepared by electrospinning process for
biomedical applications. Bead free uniform starch nanofiber along with
polycaprolactone polymer was produced using new solvent combination. The swelling
of the PCL/starch mat was 240% higher compared to pristine PCL mat. The blood
clotting time of the developed PCL/starch mat was 156 s and the contact angle was
30.8 degrees . The results suggest that the developed nanofibers exhibited good
hemostatic potential with quick rate of clotting to control blood loss in
traumatic injuries.
PMID- 29964115
TI - Chemically crosslinked hydrogel and its driving force towards superabsorbent
behaviour.
AB - Dissolved oil palm empty fruit bunch (EFB) cellulose in NaOH/urea solvent was
mixed with sodium carboxymethylcellulose (NaCMC) to form a green regenerated
superabsorbent hydrogel. The effect of concentration of epichlorohydrin (ECH) as
the crosslinker on the formation, physical, and chemical properties of hydrogel
was studied. Rapid formation and higher gel content of hydrogel were observed at
10% concentration of ECH. The superabsorbent hydrogel was successfully fabricated
in this study with the swelling ability >100,000%. Hydrogel with higher
concentration of ECH showed opposite trend by having higher superabsorbent
property than that of lower concentration. The covalent bond of COC was observed
with Attenuated total reflectance fourier transform infrared (ATR-FT-IR)
spectroscopy to confirm the occurrence of crosslinking. The physical and chemical
properties of hydrogel were affected by swelling phenomenon. Hydrogel with higher
degree of swelling exhibited lower moisture retention and higher transparency.
Moreover, the weight of the superabsorbent hydrogel increased with the decrement
of pH value of external media (distilled water). This study provided substantial
information on the effect of different percentage of ECH as crosslinker on
hydrogel basic properties. Furthermore, this study affords correlation of many
essential driving forces that affected hydrogel superabsorbent property.
PMID- 29964116
TI - Fungal polysaccharides as a water-adsorbing material in esters production with
the use of lipase from Rhizomucor variabilis.
AB - The extracellular crude Rhizomucor variabilis lipase was used for synthesis of
flavor ester butyl caprylate and 1-butyl oleate often used as a diesel additive,
a polyvinyl chloride plasticizer, a water-resisting agent, and an additive to
hydraulic fluids. The influence of various reaction parameters such as the molar
ratio, time, enzyme and substrate concentration, and effect of various fungal
polysaccharides was estimated. The rate of catalyzed synthesis of esters largely
depends on the solvent medium, and the maximum activity was found when n-hexane
was used as a solvent. The maximum conversion yield of 58.2% and 59.3% was
obtained for butyl caprylate and butyl oleate, respectively, under the following
conditions: amount of free lipase 500 U; caprylic acid:butanol molar ratio 1:1;
oleic acid:butanol molar ratio 2:1. The addition of naturally obtained fungal
polysaccharides significantly enhanced the ester synthesis. The highest
conversion rate of 95.2% was observed for butyl caprylate in the presence of
AbEPS after 24 h with 500 U of free R. variabilis lipase. In the case of butyl
oleate synthesis in the presence of LsPS, a maximum conversion yield of 91.2% was
observed after the 24-h reaction.
PMID- 29964117
TI - Anti-IIa activity and antitumor properties of a hybrid heparin/heparan sulfate
like compound from Litopenaeus vannamei shrimp.
AB - In this present study, the anti-IIa activity and the antitumor properties of a
hybrid heparin/heparan sulfate-like compound (sH/HS) from Litopenaeus vannamei
shrimp heads are related. In addition to inhibiting 90.7% of thrombin activity at
the lowest tested concentration (0.5 MUg/mL), sH/HS compound stimulated the
synthesis of antithrombotic heparan sulfate by endothelial cells in a dose
dependent manner. In vitro experiments demonstrated that the molecule from shrimp
displayed a potent anti-angiogenic effect, reducing over 80% of the tubular
structures formation at 50 and 100 MUg/mL. In addition, sH/HS compound was able
to inhibit the migration of B16F10 cells at all tested concentrations without
affecting the cell viability. Although the studied compound had no effect on the
proliferation of such cells during a period of 24 h, it had a significant long
term anti-proliferative effect, reducing about 80% of colony formation and
anchorage-independent growth at 50 and 100 MUg/mL concentrations. When its
effectiveness was tested in vivo, it was demonstrated that sH/HS promoted a
reduction of more than 90% of tumor growth. In the context of thromboembolic
disorders associated with cancer, such findings make the sH/HS compound an
excellent target for studies on inhibiting of development and tumor progression,
and the prevention of coagulopathies.
PMID- 29964119
TI - Interspecies assessment factors and skin sensitization risk assessment.
AB - For many endpoints in toxicology, an interspecies safety factor remains a
standard requirement. However, for skin sensitization, the hazard and potency
predictions, notably from the local lymph node assay (LLNA) have been shown to
correlate well with human data. Despite this, there are always exceptions, both
over and under predictions. For this reason it has been suggested that an
interspecies factor of 15 would accommodate potential "errors". An alternative
approach is suggested in which an evidence-based strategy is taken: the large
majority of the information indicates a human:LLNA ratio of 1, therefore a
corrective factor would best be applied where our knowledge of the underlying
chemistry of sensitization indicates that it is necessary.
PMID- 29964118
TI - Biochemical and functional characterization of a novel thermoacidophilic, heat
and halo-ionic liquids tolerant endo-beta-1,4-glucanase from saline-alkaline lake
soil microbial metagenomic DNA.
AB - The lignocellulosic biomass usually need pre-treatment with acid at high
temperature or solved in ionic liquid (IL) before cellulases hydrolysis. Thus,
thermoacidophilic, thermostable and IL-tolerant cellulases are greatly desired,
but rarely reported. In this study, a novel endo-beta-1,4-glucanase gene nmGH45
was directly cloned from saline-alkaline lake soil microbial metagenomic DNA and
expressed in Pichia pastoris. Recombinant NMgh45 was active and stable at pH 3.0
9.0, with maximum activity at pH 4.5 and >80% residual activities at pH 3.0-11.0.
It exhibited maximal activity at 60-70 degrees C and remaining >90% and 68%
residual activities at 80 degrees C for 2 h and 90 degrees C for 1 h. Besides,
NMgh45 retained >88% relative activities in 4 M NaCl, and was stable for 24 h.
Significantly, it was highly IL-tolerant, remaining 92.8% and 43.8% residual
activities in 10% and 20% 1-butyl-3-methylimidazolium chloride. Compared with
other non-halo-tolerant counterparts, NMgh45 was enriched with acidic amino acids
on the protein surface, and the conformation of NMgh45 was stable at high
salinity condition based on molecular dynamic simulation. Finally, the
productivity of recombinant NMgh45 was optimized at multi-levels. The
thermoacidphilic and acid-alkaline-halo-tolerant properties make NMgh45 a
promising enzyme for basic research and industrial applications.
PMID- 29964120
TI - Critique of the ACGIH 2016 derivation of toluene diisocyanate Threshold Limit
Values.
AB - In 2016, the American Conference of Governmental Industrial Hygienists (ACGIH)
lowered the 8-hr Threshold Limit Value - time-weighted average (TLV-TWA) for
toluene diisocyanate (TDI) from 5 ppb to 1 ppb, and the 15-min short-term
exposure limit (STEL) from 20 ppb to 5 ppb. We evaluated ACGIH's basis for
lowering these values. It is our opinion that the ACGIH's evaluation of the
evidence for occupational asthma and respiratory effects from TDI exposure does
not fully integrate the results of all the available human and animal studies. We
found that some studies reported occupational asthma cases at TWAs less than 5
ppb, but these cases were likely caused by peak exposures above 20 ppb. Advances
in industrial hygiene have reduced peak exposures and the incidence of upset
conditions, such as spills and accidents, in modern TDI facilities. Taken
together, the human evidence indicates that adherence to the previous 8-hr TLV
TWA and 15-min STEL (5 ppb and 20 ppb, respectively) prevents most, if not all,
cases of occupational asthma, and eliminates or reduces the risk of lung function
decrements and other respiratory effects. While limited, the animal literature
supports the human evidence and indicates that TDI-induced asthma is a threshold
phenomenon. We conclude that ACGIH's decision to lower the TLV-TWA and STEL
values for TDI is not adequately supported.
PMID- 29964121
TI - Should DTPA, an Aminocarboxylic acid (ethylenediamine-based) chelating agent, be
considered a developmental toxicant?
AB - Aminocarboxylic acid (ethylenediamine-based) chelating agents, such as DTPA and
EDTA, are widely used in a variety of products and processes. Recently the
European RAC proposed to classify DTPA as a developmental toxicant Category 1B
according to CLP. This paper provides unequivocal and significant evidence that
developmental effects cannot be considered an intrinsic property of the chelating
substances themselves since: (1) animals fed a zinc deficient diet during
gestation exhibit developmental toxicity of a similar nature and severity to that
observed in studies involving such chelates, (2) sufficient supplementation of
zinc in the diet, or administration of zinc bound chelates, completely negates
the developmental effects. Moreover, the bioavailability of DTPA is very low with
>95% of oral doses excreted unchanged via the feces within 24 h. If DTPA would
possess the intrinsic property to be developmentally toxic, simple zinc
supplementation should not be sufficient to negate these effects. Furthermore,
the relevance of classification is highly questionable since worker or consumer
exposure could not lead to a scenario whereby sufficient zinc deficiency would
manifest itself. Therefore classification of DTPA for such effects is not
protective of human health; instead it leads to onerous and disproportionate
restrictions being placed on this substance.
PMID- 29964122
TI - Inhalable multi-compartmental phospholipid enveloped lipid core nanocomposites
for localized mTOR inhibitor/herbal combined therapy of lung carcinoma.
AB - Pulmonary delivery of drug nanocarriers can overcome the shortcomings of systemic
cancer therapy via the enhanced permeability and retention (EPR) based
nanomedicine. Herein, inhalable multi-compartmental nanocomposites with the
capability for both localized and modulated release of the hydrophobic mTOR
inhibitor, rapamycin (RAP) and the hydrophilic herbal drug, berberine (BER) have
been developed for lung cancer therapy. Two types of multi-compartmental
nanocarriers were fabricated by enveloping BER hydrophobic ion pair-lipid
nanocore within a shell of RAP-phospholipid complex bilayer to reduce the
delivery gap between the two drugs. To further enhance their tumor targeting, the
nanocarriers were layer-by-layer coated by cationic lactoferrin and anionic
hyaluronate resulting in enhanced internalization and cytotoxicity against lung
cancer cells. The inhalable nanocomposites fabricated by spray-drying of multi
compartmental nanocarriers exhibited favorable aerosolization efficiency (MMAD of
3.28 um and FPF of 55.5%). The powerful anti-cancer efficacy of inhalable
nanocomposites in lung cancer bearing mice compared to the inhaled free drugs was
revealed by remarkable decrease in lung weight, and reduction in both number and
diameters of lung adenomatous foci and angiogenic markers compared to positive
control. Overall, localized delivery of RAP and BER to tumor cells via inhalable
multi-compartmental nanocomposites holds great promise in management of lung
cancer.
PMID- 29964125
TI - Structural and clinical consequences of activation loop mutations in class III
receptor tyrosine kinases.
AB - Mutations within the activation loop of members of the class III receptor
tyrosine kinase (RTK) subfamily, which includes KIT, PDGFRA, and FLT3, have been
observed in multiple human tumor types. These mutations confer constitutive
activation as well as resistance to the type II tyrosine kinase inhibitors (TKI)
that are currently clinically available, such as imatinib and sunitinib. It is
now understood that activation loop mutations in class III RTKs shift the
activation state equilibrium away from inactive states, to which type II TKIs
bind, to the active state by destabilizing the inactive conformation. Recently,
type I TKIs, which can bind to active kinase conformations, have been developed
with specificity for class III RTK members. Some type I TKIs, such as crenolanib
and avapritinib (BLU-285), have entered clinical studies for patients with
activation loop mutations in KIT, PDGFRA, or FLT3. Preliminary results suggest
that these type I TKIs show activity in these patient populations that previously
lacked effective treatments. This article reviews the inactive and active
structures of KIT, PDGFRA, and FLT3, how the mutations seen in human cancers
affect kinase structure, and the clinical implications of these mutations in
terms of type I vs. type II TKI binding.
PMID- 29964124
TI - Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK
inhibitors.
AB - Many new drugs have appeared in last years in the oncological treatment scenario.
Each drug carries an important set of adverse events, not less, cardiovascular
adverse events. This aspect is even more important considering the increasing use
of combination therapies with two drugs, or three drugs as in some ongoing
clinical trials. Besides it represents a growing problem for Cardiologists, that
face it in every day clinical practice and that will face it probably more and
more in the coming years. This work reviews the mechanism of action of BRAF
inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms
that lead to cardiovascular toxicity. Particularly, it focuses on hypertension
and ejection fraction reduction development. Then, it follows the examination of
published data for each combination therapy. A Literature research was carried
out using Pubmed selecting review articles, original studies and clinical trials,
but mainly focusing on phase 3 studies. This work aims to summarize the knowledge
about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity
to make it usable and give the basic tools to Cardiologists and Oncologists for a
better management of cancer patient undergoing this treatment. Besides a deeper
knowledge of the cardiovascular adverse events linked to this treatment and the
magnitude of their expression and frequency can lead to a targeted cardiological
treatment.
PMID- 29964126
TI - Ga-labeled Prostate-specific Membrane Antigen Ligand-positron-emission
Tomography: Still Just the Tip of the Iceberg.
AB - OBJECTIVES: To assess the performance of Ga-labeled prostate-specific membrane
antigen ligand-positron-emission tomography (Ga-PSMA PET) for positive lymph
nodes on imaging after curatively intended radical prostatectomy. PATIENTS AND
METHODS: Seventeen patients with biochemical recurrence after radical
prostatectomy undergoing robot-assisted salvage lymphadenectomy for positive
lymph nodes on imaging were included in this single surgeon study. The
performance of Ga-PSMA PET was assessed on per patient, per lesion, per landing
site and per laterality level using sensitivity, specificity, and negative and
positive predictive value analysis. RESULTS: A total of 34 positive nodes were
detected on Ga-PSMA PET with a median of 2 nodes per patient (IQR 1-3 nodes per
patient). Sixty six nodes were pathologically disease positive from 14 patients,
with a median of 2 positive nodes per patient (IQR 1-6). Three patients had no
pathologically detectable disease. On a per patient basis, the positive
predictive value was 82%. Sensitivity, specificity, and negative predictive value
were not able to be calculated as all patients had disease recurrence with a
detectable prostate-specific antigen.On a "per lesion" basis, the sensitivity,
specificity, positive predictive value, and negative predictive value were 36.7%,
96.9%, 73.5%, and 86.7%, respectively. CONCLUSION: Our study indicates that
sensitivity of Ga-PSMA PET in the salvage setting is not yet sufficient to detect
all sites of metastasis. Therefore, imaging-guided metastasis targeted treatment
is likely to fail given the likely concomitant imaging negative more widespread
disease.
PMID- 29964127
TI - Predictive Analytics and Modeling Employing Machine Learning Technology: The Next
Step in Data Sharing, Analysis, and Individualized Counseling Explored With a
Large, Prospective Prenatal Hydronephrosis Database.
AB - OBJECTIVE: To explore the potential value of utilizing a commercially available
cloud-based machine learning platform to predict surgical intervention in infants
with prenatal hydronephrosis (HN). MATERIALS AND METHODS: A prospective prenatal
HN database was uploaded into Microsoft Azure Machine Learning Studio.
Probabilistic principal component analysis was employed for data imputation.
Multiple clinical variables were included in two-class decision jungle and neural
network for model training, using surgical intervention as the primary outcome.
Models were scored and evaluated after a 70/30 split of the data. RESULTS: A
total of 557 entries were included. The optimized model (decision jungle)
achieved an area under the curve of 0.9, accuracy of 0.87, and precision of 0.80,
employing a threshold of 0.5 to predict surgery. Average time to train, score and
evaluate the model was 5 seconds. The predictive model was deployed as a web
service in 35 seconds, generating a unique API key for app and webpage
development. Individualized prediction based on the included variables was
deployed as a web-based and batch execution Excel file in less than one minute.
CONCLUSION: This cloud-based ML technology allows easy building, deployment, and
sharing of predictive analytics solutions. Using prenatal HN as an example, we
propose an opportunity to address contemporary challenges with data analysis,
reporting a creative solution that moves beyond the current standard.
PMID- 29964123
TI - Prospective for cytochrome P450 epoxygenase cardiovascular and renal
therapeutics.
AB - Therapeutics for arachidonic acid pathways began with the development of non
steroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX). The
enzymatic pathways and arachidonic acid metabolites and respective receptors have
been successfully targeted and therapeutics developed for pain, inflammation,
pulmonary and cardiovascular diseases. These drugs target the COX and
lipoxygenase pathways but not the third branch for arachidonic acid metabolism,
the cytochrome P450 (CYP) pathway. Small molecule compounds targeting enzymes and
CYP epoxy-fatty acid metabolites have evolved rapidly over the last two decades.
These therapeutics have primarily focused on inhibiting soluble epoxide hydrolase
(sEH) or agonist mimetics for epoxyeicosatrienoic acids (EET). Based on
preclinical animal model studies and human studies, major therapeutic indications
for these sEH inhibitors and EET mimics/analogs are renal and cardiovascular
diseases. Novel small molecules that inhibit sEH have advanced to human clinical
trials and demonstrate promise for cardiovascular diseases. Challenges remain for
sEH inhibitor and EET analog drug development; however, there is a high
likelihood that a drug that acts on this third branch of arachidonic acid
metabolism will be utilized to treat a cardiovascular or kidney disease in the
next decade.
PMID- 29964128
TI - Predictors of Benign Uretero-enteric Anastomotic Strictures After Radical
Cystectomy and Urinary Diversion.
AB - OBJECTIVE: To determine predictors of symptomatic uretero-enteric anastomotic
strictures (UAS) formation following radical cystectomy (RC) and urinary
diversion (UD). MATERIALS AND METHODS: 2,888 consecutive patients who underwent
open RC at our institution from 1995-2014 were included for analysis. Data was
collected from institutional databases and individual medical records.
Symptomatic benign UAS was defined as percutaneous nephrostomy tube insertion for
rising creatinine or unilateral hydronephrosis comparing pre- and post-operative
imaging. Univariate and multivariable Cox proportional hazards models were
utilized to identify features associated with UAS formation. RESULTS: UAS
developed in 123/2,888 patients following RC. There were 94 symptomatic and 29
asymptomatic strictures. Median follow-up was 32 months (IQR 12, 72) for patients
without stricture. Higher BMI (p=0.002), ASA score >2 (p<0.0001), lymph node
positive disease (p=0.027) and 30-day post-operative complications grade 3+
(p=0.017) on univariate analysis and male gender on multivariable analysis were
significantly associated with time to stricture development. However, history of
prior abdominal surgery (PAS) had the strongest association with time to
stricture formation (HR 3.25, 95% CI 1.78, 5.94, p=0.0001). Risk of developing a
stricture within 10 years was 1.9% for patients without PAS vs. 9.3% with PAS.
CONCLUSIONS: Associated factors with increased risk of benign UAS include higher
BMI, ASA score >2, lymph node involvement, grade III/IV complications within 30
days, male sex, and a history of PAS. We conclude that while surveillance is
important for patients who undergo cystectomy for malignancy, it may be
beneficial for patients with history of PAS undergo more intensive follow-up
compared to those patients without history of PAS.
PMID- 29964129
TI - Ureteroscopic Management of Large >=2 cm Upper Tract Urothelial Carcinoma: A
Comprehensive 23-Year Experience.
AB - OBJECTIVE: To evaluate the effectiveness of ureteroscopy (URS) with laser
ablation as an alternative treatment for upper tract urothelial carcinoma (UTUC)
lesions larger than 2 cm. Traditionally, patients with large UTUC are treated
with radical nephroureterectomy (RNU). However, in patients with pre-existing
renal disease, a solitary kidney, or those who decline RNU, management of UTUC
may prove challenging METHODS: An institutional database review identified 80
patients with biopsy proven low-grade UTUC who had at least one lesion larger
than 2 cm. We collected clinical data including demographics, operative
parameters, and pathologic features. Follow-up for all patients was standardized
and included cystoscopy and URS every 3 months until clear, every 6 months
through the fifth year, and yearly thereafter. We calculated rates of recurrence,
progression, and overall survival. RESULTS: In total, 86 unique lesions >=2cm
were identified in the 80 qualifying patients; mean tumor size was 3.04 cm.
Median follow-up was 43.6 months. During follow-up of patients treated
curatively, 90.5% of tumors had ipsilateral recurrence and 31.7% progressed in
grade at a median of 26.3 months. RNU was performed in 16 patients (20%); mean
time to surgery was 23.2 months. Overall survival was 75%, and cancer specific
survival was 84% at 5-year follow-up. CONCLUSION: Under strict surveillance,
ureteroscopic management of large (>= 2cm) UTUC lesions is a viable treatment
alternative to RNU. While recurrence is common, URS can potentially preserve
renal units in patients with large lesions.
PMID- 29964130
TI - The Design and Implementation of a Physician-Staffed, Referral-Based Advance
Directive Clinic at an Academic Medical Center.
PMID- 29964131
TI - Adaptive response of yeast cells to triggered toxicity of phosphoribulokinase.
AB - Adjustment of plasmid copy number resulting from the balance between positive and
negative impacts of borne synthetic genes, plays a critical role in the global
efficiency of multistep metabolic engineering. Differential expression of co
expressed engineered genes is frequently observed depending on growth phases,
metabolic status and triggered adjustments of plasmid copy numbers, constituting
a dynamic process contributing to minimize global engineering burden. A yeast
model involving plasmid based expression of phosphoribulokinase (PRKp), a key
enzyme for the reconstruction of synthetic Calvin cycle, was designed to gain
further insights into such a mechanism. A conditional PRK expression cassette was
cloned either onto a low (ARS-CEN based) or a high (2-micron origin based) copy
number plasmid using complementation of a trp1 genomic mutation as constant
positive selection. Evolution of plasmid copy numbers, PRKp expressions, and cell
growth rates were dynamically monitored following gene de-repression through
external doxycycline concentration shifts. In the absence of RubisCO encoding
gene permitting metabolic recycling, PRKp expression that led to depletion of
ribulose phosphate, a critical metabolite for aromatic amino-acids biosynthesis,
and accumulation of the dead-end diphosphate product contribute to toxicity.
Triggered copy number adjustment was found to be a dynamic process depending both
on plasmid types and levels of PRK induction. With the ARS-CEN plasmid, cell
growth was abruptly affected only when level PRKp expression exceeded a threshold
value. In contrast, a proportional relationship was observed with the 2-micron
plasmid consistent with large copy number adjustments. Micro-compartment
partitioning of bulk cultures by embedding individual cells into inverse culture
medium/oil droplets, revealed the presence of slow and fast growing
subpopulations that differ in relative proportions for low and high copy number
plasmids.
PMID- 29964132
TI - JBP485 attenuates vancomycin-induced nephrotoxicity by regulating the expressions
of organic anion transporter (Oat) 1, Oat3, organic cation transporter 2 (Oct2),
multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein (P-gp) in
rats.
AB - The present study aimed to investigate the regulation of JBP485 on the
expressions of renal organic anion transporter (Oat) 1, Oat3, organic cation
transporter 2 (Oct2), multidrug resistance-associated protein 2 (Mrp2) and P
glycoprotein (P-gp), which can accelerate the renal excretion of accumulated
endogenous toxins to attenuate vancomycin-induced nephrotoxicity (VIN) in rats.
Vancomycin suppressed the mRNA and protein expressions of Oat1, Oat3, Oct2, Mrp2
and P-gp to reduce the renal excretion of endogenous toxins (e.g. indoxyl
sulfate). However, JBP485 could reverse these effects and improved the
pathological condition and morphology of rat kidney with a decrease in wet
weight. Moreover, JBP485 decreased the number of apoptosis cells in TUNEL
staining as well as reversed the decreased expression of B-cell lymphoma-2 (Bcl
2) and the increased expressions of Bcl-2-like protein 4 (Bax) and Caspase-3 in
rat kidney. In addition, JBP485 also increased the level of superoxide dismutase
(SOD) and decreased the level of malondialdehyde (MDA) in rat kidney. But JBP485
did not affect the plasma concentrations of vancomycin. In conclusion, the
mechanism of VIN might be involved in, at least in part, suppressing the
expressions of Oat1, Oat3, Oct2, Mrp2 and P-gp, and JBP485 could attenuate VIN in
rats.
PMID- 29964133
TI - The effect of light sensitizer localization on the stability of indocyanine green
liposomes.
AB - Light triggered drug delivery systems offer attractive possibilities for
sophisticated therapy, providing both temporal and spatial control of drug
release. We have developed light triggered liposomes with clinically approved
indocyanine green (ICG) as the light sensitizing compound. Amphiphilic ICG can be
localized in different compartments of the liposomes, but the effect of its
presence, on both triggered release and long term stability, has not been
studied. In this work, we report that ICG localization has a significant effect
on the properties of the liposomes. Polyethylene glycol (PEG) coating of the
liposomes leads to binding and stabilization of the ICG molecules on the surface
of the lipid bilayer. This formulation showed both good storage stability in
buffer solution (at +4-37 degrees C) and adequate stability in serum and
vitreous (at +37 degrees C). The combination of ICG within the lipid bilayer and
PEG coating lead to poor stability at elevated temperatures of +22 degrees C and
+ 37 degrees C. The mechanisms of the increased instability due to ICG insertion
in the lipid bilayer was elucidated with molecular dynamics simulations.
Significant PEG insertion into the bilayer was induced in the presence of ICG in
the lipid bilayer. Finally, feasibility of freeze-drying as a long term storage
method for the ICG liposomes was demonstrated. Overall, this is the first
detailed study on the interactions of lipid bilayer, light sensitizer (ICG) and
PEG coating on the liposome stability. The localization of the light triggering
agent significantly alters the structure of the liposomes and it is important to
consider these aspects in triggered drug delivery system design.
PMID- 29964134
TI - Immune responses induced by nano-self-assembled lipid adjuvants based on a
monomycoloyl glycerol analogue after vaccination with the Chlamydia trachomatis
major outer membrane protein.
AB - Nanocarriers based on inverse hexagonal liquid crystalline phases (hexosomes)
show promising potential as vaccine delivery systems. Their unique internal
structure, composed of both lipophilic domains and water-containing channels,
renders them capable of accommodating immunopotentiating compounds and antigens.
However, their adjuvant properties are poorly understood. We hypothesized that
the supramolecular structure of the lyotropic liquid crystalline phase influences
the immunostimulatory activity of lipid-based nanocarriers. To test this,
hexosomes were designed containing the lipid phytantriol (Phy) and the
immunopotentiator monomycoloyl glycerol-1 (MMG-1). Self-assembly of Phy and MMG-1
into nanocarriers featuring an internal hexagonal phase was confirmed by small
angle X-ray scattering and cryogenic transmission electron microscopy. The effect
of the nanostructure on the adjuvant activity was studied by comparing the
immunogenicity of Phy/MMG-1 hexosomes with MMG-1-containing lamellar liquid
crystalline nanoparticles (liposomes, CAF04). The quality and magnitude of the
elicited immune responses were determined after vaccination of CB6/F1 mice using
the Chlamydia trachomatis major outer membrane protein (MOMP) as antigen. MMG-1
based hexosomes potentiated significantly stronger MOMP-specific humoral
responses than CAF04 liposomes. The liposome-based vaccine formulation induced a
much stronger MOMP-specific cell-mediated immune response compared to hexosome
adjuvanted MOMP, which elicited minimal MOMP-specific T-cell stimulation after
vaccination. Hence, our data demonstrates that hexosomal and liposomal adjuvants
activate the immune system via different mechanisms. Our work provides valuable
insights into the adjuvant potential of hexosomes and emphasizes that engineering
of the supramolecular structure can be used to design adjuvants with customized
immunological properties.
PMID- 29964135
TI - Polymer-based carriers for ophthalmic drug delivery.
AB - Despite the wide range of diseases affecting the eye, ocular bioavailability
remains a challenge in ophthalmic drug delivery. Nowadays an extensive variety of
polymers are being explored to develop colloidal drug carriers which show better
performance than the more popular drug solutions. For instance, regardless of the
type of polymer used, these systems prolong the residence time of the drug in the
absorption site with respect to conventional aqueous eye drops which are rapidly
cleared from eye surface. Furthermore, colloidal drug carriers can be
internalized by cells. In addition, positively charged particles penetrate the
cornea more effectively than neutral or negatively charged ones. These phenomena
lead to higher ocular bioavailability. This review overviews the different
polymers available to produce drug-loaded gels, microparticles and nanoparticles,
highlighting the advantageous features and biocompatibility of each polymer and
the major achievements in the field of ocular delivery. In addition, the design
of more complex delivery systems that combine several delivery platforms is
presented. Finally, regulatory aspects relevant to the clinical translation of
advanced ophthalmic drug delivery systems are also discussed. All together, this
manuscript is aimed at guiding pharmaceutical research and development towards
the rationale polymer selection to produce drug delivery systems that improve the
performance of drugs for the therapy of ophthalmic diseases.
PMID- 29964136
TI - An inhibitor screen identifies histone-modifying enzymes as mediators of polymer
mediated transgene expression from plasmid DNA.
AB - Effective transgene expression in mammalian cells relies on successful delivery,
cytoplasmic trafficking, and nuclear translocation of the delivered vector, but
delivery is impeded by several formidable physicochemical barriers on the surface
of and within the target cell. Although methods to overcome cellular exclusion
and endosomal entrapment have been studied extensively, strategies to overcome
inefficient nuclear entry and subsequent intranuclear barriers to effective
transient gene expression have only been sparsely explored. In particular, the
role of nuclear packaging of DNA with histone proteins, which governs endogenous
gene expression, has not been extensively elucidated in the case of exogenously
delivered plasmids. In this work, a parallel screen of small molecule inhibitors
of chromatin-modifying enzymes resulted in the identification of class I/II
HDACs, sirtuins, LSD1, HATs, and the methyltransferases EZH2 and MLL as targets
whose inhibition led to the enhancement of transgene expression following polymer
mediated delivery of plasmid DNA. Quantitative PCR studies revealed that HDAC
inhibition enhances the amount of plasmid DNA delivered to the nucleus in UMUC3
human bladder cancer cells. Native chromatin immunoprecipitation (N-ChIP)-qPCR
experiments in CHO-K1 cells indicated that plasmids indeed interact with
intracellular core Histone H3, and inhibitors of HDAC and LSD1 proteins are able
to modulate this interaction. Pair-wise treatments of effective inhibitors led to
synergistic enhancement of transgene expression to varying extents in both cell
types. Our results demonstrate that the ability to modulate enzymes that play a
role in epigenetic processes can enhance the efficacy of non-viral gene delivery,
resulting in significant implications for gene therapy and industrial
biotechnology.
PMID- 29964137
TI - On the way to precision formulation additives: 2D-screening to select
solubilizers with tailored host and release capabilities.
AB - A 2-dimensional high-throughput screening method is presented to select peptide
sequences from large peptide libraries for precision formulation additives,
having a high capacity to specifically host a drug of interest and provide
tailored drug release properties. The identified sequences are conjugated with
poly(ethylene glycol) (PEG) to obtain peptide-PEG conjugates that proved to be
valuable as solubilizers for small organic molecule drugs to overcome limitations
of poor water-solubility and low bio-availability. The 2D-screening method
selects peptide sequences on both (i) high loading capacities and (ii) preferred
drug-release capabilities as demonstrated on an experimental Tau-protein
aggregation inhibitor/Tau- deaggregator with potentials for an anti-Alzheimer
disease drug (BB17). To enable 2D-screening, a one-bead one-compound (OBOC)
peptide library was immobilized on a glass slide, allocating individual beads to
permanent positions. While the first screening step involved incubation of the
supported OBOC library with BB17 to identify beads with high drug binding
capacities by fluorescence scanner readouts, the second step reveals release
properties of the high capacity binders by incubation with blood plasma protein
model solutions. Efficiently peptides with high BB17 capacities and either keeper
or medium or fast releaser properties can be identified by direct sequence
readouts from the glass slide supported resin beads via matrix-assisted laser
desorption/ionization time-of-flight tandem mass spectrometry. Four peptides are
synthesized as peptide-PEG solubilizers representing strong, medium, weak
releasers and non-binders. Loading capacities reached up to 1:3.4 (mol drug per
mol carrier) and release kinetics (fast/medium/slow) are in agreement with the
selection process as investigated by fluorescence anisotropy and fluorescence
correlation spectroscopy. The ability of BB17/conjugate complexes to inhibit the
aggregation of Tau4RDDeltaK (four repeat Tau ((M)Q244-E372 with deletion of
K280), 129 residues) in N2a cells is studied by a Tau-pelleting assay showing the
modulation of cellular Tau aggregation. Promising effects such as the reduction
of 55% of total Tau load are observed for the strong releaser additive. Studies
of in vitro Thioflavin S Tau-aggregation assays show half-maximal inhibitory
activities (IC50 values) of BB17/conjugates in the low micro-molar range.
PMID- 29964138
TI - Hemoglobin E protects against acute Plasmodium vivax infections in a Kachin
population at the China-Myanmar border.
AB - OBJECTIVES: Hemoglobin E (HbE, beta26 Glu-Lys) is the most prevalent
hemoglobinopathy in Southeast Asia. This study aimed to determine whether HbE
protects against clinical Plasmodium vivax malaria in Southeast Asia. METHODS: In
a case-control study performed in villages along the China-Myanmar border, we
determined the prevalence of HbE in 257 villagers who had acute P. vivax
infections and in 157 control healthy villagers. RESULTS: HbE in P. vivax
patients (17.4%) was significantly less prevalent than in the healthy villager
population (36.3%). Moreover, there was a complete lack of HbEE homozygotes in
the vivax patients as compared to 9.5% prevalence in the healthy villagers. Using
the HbAA group as the reference, both the HbEA heterozygotes and HbEE homozygotes
had significantly lower odds of presenting with acute P. vivax infections.
Furthermore, HbEA heterozygotes also had significantly lower P. vivax asexual
parasite densities. HbEA did not affect the proportion of P. vivax patients with
gametocytemia nor the gametocyte densities. CONCLUSIONS: HbE offers significant
protection against the occurrence and parasite density of acute P. vivax
infections and provides a renewed perspective on P. vivax malaria as a
potentially strong driving force behind the high frequencies of HbE in the Kachin
population.
PMID- 29964139
TI - Population structure of invasive Neisseria meningitidis in the United States,
2011-15.
AB - OBJECTIVES: Meningococcal conjugate vaccines (MenACWY) were licensed in the
United States in 2005. We assessed the population structure of invasive Neisseria
meningitidis (Nm) ten years after recommended use of MenACWY among adolescents.
METHODS: Meningococcal isolates obtained through Active Bacterial Core
surveillance (ABCs) from 2000-05, 2006-10, and 2011-15 underwent whole genome or
Sanger sequencing. Genome phylogenies were completed using maximum likelihood
methods; and distribution of multilocus sequence typing (MLST) sequence type (ST)
and clonal complex (CC), and PorA and FetA types were assessed. RESULTS:
Prevalent serogroups (B, C, Y and W), CCs, and PorA and FetA types were detected
in all three time periods, but dynamic changes were observed. The proportion of
serogroup W CC11 isolates increased in 2011-15 and were most related to South
American strains. Changes in CC distribution were also observed in serogroup C
and serogroup Y. Phylogenetic analysis showed that U.S. serogroup W CC11s are
closely related to a subset of U.S. serogroup C isolates; combined global
analysis demonstrated that some CCs, including CC11, exhibit regional clustering.
CONCLUSIONS: Overall, the Nm population structure has remained stable after
MenACWY introduction. Dynamic changes in genotypes, unlikely related to
vaccination, also occurred, highlighting the need for continued whole genome
based surveillance.
PMID- 29964140
TI - The relative invasive disease potential of Streptococcus pneumoniae among
children after PCV introduction: A systematic review and meta-analysis.
AB - OBJECTIVES: Burden of pneumococcal disease depends on the prevalence and invasive
disease potential of serotypes. We aimed to estimate the invasive disease
potential of serotypes in children under 5 years of age by combining data from
different settings with routine immunisation with pneumococcal conjugate vaccines
(PCV). METHODS: We conducted a systematic review, supplemented by unpublished
data, to identify data on the frequency of pneumococcal serotypes in carriage and
invasive pneumococcal disease (IPD). We estimated the invasive disease potential
of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI)
compared with 19A (reference serotype) by meta-analysis. We report results based
on a random effects model for children aged 0-23, 24-29, and 0-59 months and by
invasive clinical syndromes. RESULTS: In comparison with 19A, serotypes 1, 7F,
and 12F had a significantly higher invasive disease potential in children aged 0
23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non
vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a
lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F
were at the upper end of the invasiveness spectrum. CONCLUSIONS: There is
substantial variation among pneumococcal serotypes in their potential to cause
IPD and disease presentation, which is influenced by age and time after PCV
introduction. Surveillance of IPD and carriage is critical to understand the
expected effectiveness of current PCVs (in the longer term) and guide the
development of future vaccines.
PMID- 29964141
TI - Diagnostic value of symptoms and signs for identifying urinary tract infection in
older adult outpatients: Systematic review and meta-analysis.
AB - OBJECTIVES: To critically appraise and evaluate the diagnostic value of symptoms
and signs in identifying UTI in older adult outpatients, using evidence from
observational studies. METHODS: We searched Medline and Medline in process,
Embase and Web of Science, from inception up to September 2017. We included
studies assessing the diagnostic accuracy of symptoms and/or signs in predicting
UTI in outpatients aged 65 years and above. Study quality was assessed using the
QUADAS-2 tool. RESULTS: We identified 15 eligible studies of variable quality,
with a total of 12,039 participants (range 65-4259), and assessed the diagnostic
accuracy of 66 different symptoms and signs in predicting UTI. A number of
symptoms and signs typically associated with UTI, such as nocturia, urgency and
abnormal vital signs, were of limited use in older adult outpatients. Inability
to perform a number of acts of daily living were predictors of UTI: For example,
disability in feeding oneself, + ve LR: 11.8 (95% CI 5.51-25.2) and disability in
washing one's hands and face, + ve LR: 6.84 (95% CI 4.08-11.5). CONCLUSIONS: The
limited evidence of varying quality shows that a number of symptoms and signs
traditionally associated with UTI may have limited diagnostic value in older
adult outpatients.
PMID- 29964142
TI - Diverse bacterial species contribute to antibiotic-associated diarrhoea and
gastrointestinal damage.
AB - OBJECTIVES: Antibiotic-associated diarrhoea (AAD) caused by C. difficile is one
of the most common nosocomial infections, however, little is known about
infections related to antimicrobial use for pathogens other than C. difficile. We
therefore aimed to provide insight into other bacterial causes of AAD, and how
infection with these pathogens causes damage in the dysbiotic gut. METHODS:
Clinical isolates from C. difficile-negative AAD patients were whole genome
sequenced for in silico analysis of potential virulence factors and antimicrobial
resistance determinants. A mouse model of infection was developed to assess the
capacity of these isolates to cause gastrointestinal damage, which was analysed
by studying specific markers in the gastrointestinal mucosa of infected mice.
RESULTS: Several bacterial pathogens were isolated from patients with C.
difficile-negative AAD. Each isolate showed the potential for virulence based on
encoded virulence factors, as well as most showing antimicrobial resistance in
vitro. Isolates of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella
pneumoniae were tested in the mouse model of infection, inducing damage primarily
in the small intestine, affecting adherens junction integrity, cellular polarity,
and cellular proliferation. CONCLUSIONS: Several pathogens of clinical importance
other than C. difficile are able to cause gastrointestinal infection following
antimicrobial-mediated dysbiosis. The virulence potential and multidrug
resistance identified in these isolates illuminates the importance of further
diagnostic screening in cases of C. difficile-negative AAD.
PMID- 29964143
TI - Utility of GeneXpert in analysis of bronchoalveolar lavage samples from patients
with suspected tuberculosis in an intermediate-burden setting.
AB - OBJECTIVES: To explore the clinical role of GeneXpert in managing pulmonary
tuberculosis (TB) in an intermediate burden city. METHODS: Sputum acid-fast
bacilli (AFB) smear negative patients underwent bronchoscopy for bronchial
alveolar lavage (BAL). Fluids collected were examined for AFB smear, TB culture,
TB polymerase chain reaction (PCR) (Cobas Taqman) and for GeneXpert. RESULTS:
From October 2015 to February 2017, 227 BAL samples were collected. Cough and
haemoptysis were the presenting symptoms in 70.0% and 37.4%, respectively. Apical
shadows on chest X-rays (CXR) and apical cavitations on computed tomography (CT)
were commoner in GeneXpert positive cases (p = 0.01 and 0.02, respectively).
Sensitivity and specificity of GeneXpert for TB diagnosis was 80% and 98%
respectively. Positive and negative predictive value of the test was 92.3 and
95.1%, respectively. There were 9 false negative GeneXpert samples (8 were Cobas
Taqman TB PCR negative): 6 were diagnosed by BAL culture, 2 by biopsy and one by
Cobas Taqman TB PCR. There were 3 false positive cases with negative culture; 2
were put on empirical treatment with favourable clinical responses, while one
defaulted follow-p. CONCLUSION: GeneXpert in BAL samples has high sensitivity and
specificity. It enabled timely initiation of anti-TB treatment in clinical
suspicious cases.
PMID- 29964144
TI - Fast scanning calorimetry of lysozyme unfolding at scanning rates from 5 K/min to
500,000 K/min.
AB - BACKGROUND: Protein denaturation is often studied using differential scanning
calorimetry (DSC). However, conventional instruments are limited in the
temperature scanning rate available. Fast scanning calorimetry (FSC) provides an
ability to study processes at much higher rates while using extremely small
sample masses [ng]. This makes it a very interesting technique for protein
investigation. METHODS: A combination of conventional DSC and fast scanning
calorimeters was used to study denaturation of lysozyme dissolved in glycerol.
Glycerol was chosen as a solvent to prevent evaporation from the micro-sized
samples of the fast scanning calorimeter. RESULTS: The lysozyme denaturation
temperatures in the range of scanning rates from 5 K/min to ca. 500,000 K/min
follow the Arrhenius law. The experimental results for FSC and conventional DSC
fall into two distinct clusters in a Kissinger plot, which are well approximated
by two parallel straight lines. CONCLUSIONS: The transition temperatures for the
unfolding process measured on fast scanning calorimetry sensor are significantly
lower than what could be expected from the results of conventional DSC using
extrapolation to high scanning rates. Evidence for the influence of the relative
surface area on the unfolding temperature was found. GENERAL SIGNIFICANCE: For
the first time, fast scanning calorimetry was employed to study protein
denaturation with a range of temperature scanning rates of 5 orders of magnitude.
Decreased thermal stability of the micro-sized samples on the fast scanning
calorimeter raise caution over using bulk solution thermal stability data of
proteins for applications where micro-sized dispersed protein solutions are used,
e.g., spray drying.
PMID- 29964145
TI - Approaches to community consultation in exception from informed consent: Analysis
of scope, efficiency, and cost at two centers.
AB - OBJECTIVES: Community consultation (CC) is fundamental to the Exception from
Informed Consent (EFIC) process for emergency research, designed to inform and
receive feedback from the target study population about potential risks and
benefits. To better understand the effectiveness of different techniques for CC,
we evaluated EFIC processes at two centers participating in a trial of early
cardiac catheterization following out-of-hospital cardiac arrest. METHODS: We
studied the Institutional Review Board-approved CC activities at Maine Medical
Center (MMC) and University of Arizona (AZ) in support of NCT02387398. In Maine,
the public was consulted by survey at a professional basketball game and in the
emergency department waiting room (in-person group), by multimedia direction to
an online website (online group), and by mail (mailing group). Arizona
respondents were either approached at a county fair (in-person group) or were
directed to an online survey (online group) via social media advertising.
RESULTS: Among 2185 survey respondents, approval rates were high for community
involvement and personal participation without individual consent. Community
consultation using in-person, online, and mailed surveys offered slightly
different approval rates, and the rate of responses by modality differed by age
and education level but not ethnicity. Print advertising was the least cost
effective at $442 per completed survey. CONCLUSIONS: Canvassing at public events
was the most efficient mode of performing CC, with approval rates similar to
mailings, online surveys, and canvassing in other locations. Print advertisements
in local papers had a low yield and cost more than other approaches.
PMID- 29964146
TI - Electro-clinical characteristics and prognostic significance of post anoxic
myoclonus.
AB - OBJECTIVE: To systematically examine the electro-clinical characteristics of post
anoxic myoclonus (PAM) and their prognostic implications in comatose cardiac
arrest (CA) survivors. METHODS: Fifty-nine CA survivors who developed myoclonus
within 72 h of arrest and underwent continuous EEG monitoring were included in
the study. Retrospective chart review was performed for all relevant clinical
variables including time of PAM onset ("early onset" when within 24 h) and
semiology (multi-focal, facial/ocular, whole body and limbs only). EEG findings
including background, reactivity, epileptiform patterns and EEG correlate to
myoclonus were reviewed at 6, 12, 24, 48 and 72 h after the return of spontaneous
circulation (ROSC). Outcome was categorized as either with recovery of
consciousness (Cerebral Performance Category (CPC) 1-3) or without recovery of
consciousness (CPC 4-5) at the time of discharge. RESULTS: Seven of the 59
patients (11.9%) regained consciousness, including 6/51 (11.8%) with early onset
PAM. Patients with recovery of consciousness had shorter time to ROSC, and were
more likely to have preserved brainstem reflexes and normal voltage background at
all times. No patient with suppression burst or low voltage background (N = 52)
at any point regained consciousness. In the subset where precise electro-clinical
correlation was possible, all (5/5) those with recovery of consciousness had
multi-focal myoclonus and most (4/5) had midline-maximal spikes over a continuous
background. No patient with any other semiology (N = 21) regained consciousness.
CONCLUSIONS: Early onset PAM is not always associated with lack of recovery of
consciousness. EEG can help discriminate between patients who may or may not
regain consciousness by the time of hospital discharge.
PMID- 29964148
TI - Guidelines for multiple imputations in repeated measurements with time-dependent
covariates: a case study.
AB - OBJECTIVES: We provide guidelines for handling the most common missing data
problems in repeated measurements in observational studies and deal with
practicalities in producing imputations when there are many partly missing time
varying variables and repeated measurements. STUDY DESIGN AND SETTING: The
Maastricht Study on long-term dementia care environments was used as a case
study. The data contain 84 momentary assessments for each of 115 participants. A
continuous outcome and several time-varying covariates were involved containing
missing observations varying from 4% to 25% per time point. A multiple imputation
procedure is advocated with restrictions imposed on the relation within and
between partially missing variables over time. RESULTS: Multiple imputation is a
better approach to deal with missing observations in both outcome and independent
variables. Furthermore, using the statistical package R-MICE, it is possible to
deal with the limitations of current statistical software in imputation of
missing observations in more complex data. CONCLUSION: In observational studies,
the direct likelihood approach (i.e., the standard longitudinal data methods) is
sufficient to obtain valid inferences in the presence of missing data only in the
outcome. In contrast, multiple imputation is required when dealing with partly
missing time-varying covariates and repeated measurements.
PMID- 29964147
TI - Acrolein induces ribotoxic stress in human cancer cells regardless of p53 status.
AB - Acrolein (Acr) cytotoxicity contributes to chemotherapeutic activity of
cyclophosphamide via metabolism of the anticancer drug. Our previous studies have
shown that Acr causes ribosomal DNA (rDNA) damages, thus shuts down ribosomal RNA
(rRNA) synthesis and leads to ribosomal stress in human cancer cells. Ribosome
senses stress in 28S rRNA and induces subsequent activation of mitogen-activated
protein kinase (MAPK) pathway which triggers ribotoxic stress response (RSR).
Here, we report that cells harboring p53 or not responds differently to Acr
induced RSR. Our results show that Acr induced rRNA cleavage via the activated
caspases in cancer cells with wild type p53, but not in cells with deficient p53.
Furthermore, MAPK pathways were activated by Acr in cancer cells regardless of
p53 status. Acr induced apoptosis in cells with wild type p53, while it induced
G2/M cell cycle arrest in cancer cells with deficient p53. In conclusion, the
presence of functional p53 plays a significant role in the mechanisms of Acr
induced rRNA cleavage and cell fates. Our results enhance our understanding of
the molecular mechanisms of Acr-mediated antitumor activity which helps develop
better therapeutic strategies for killing cancer cells with different p53 status.
PMID- 29964149
TI - PTEN is indispensable for cells to respond to MAPK inhibitors in myeloid
leukemia.
AB - Constitutively activated MAPK and AKT signaling pathways are often found in solid
tumors and leukemias. PTEN is one of the tumor suppressors that are frequently
found deficient in patients with late-stage cancers or leukemias. In this study
we demonstrate that a MAPK inhibitor, PD98059, inhibits both AKT and ERK
phosphorylation in a human myeloid leukemia cell line (TF-1), but not in PTEN
deficient leukemia cells (TF-1a). Ectopic expression of wild-type PTEN in myeloid
leukemia cells restored cytokine responsiveness at physiological concentrations
of GM-CSF (<0.02 ng/mL) and significantly improved cell sensitivity to MAPK
inhibitor. We also found that Early Growth Response 1 (EGR1) was constitutively
over-expressed in cytokine-independent TF-1a cells, and ectopic expression of
PTEN down-regulated EGR1 expression and restored dynamics of EGR1 expression in
response to GM-CSF stimulation. Data from primary bone marrow cells from mice
with Pten deletion further supports that PTEN is indispensible for myeloid
leukemia cells in response to MAPK inhibitors. Finally, We demonstrate that the
absence of EGR1 expression dynamics in response to GM-CSF stimulation is one of
the mechanisms underlying drug resistance to MAPK inhibitors in leukemia cells
with PTEN deficiency. Our data suggest a novel mechanism of PTEN in regulating
expression of EGR1 in hematopoietic cells in response to cytokine stimulation. In
conclusion, this study demonstrates that PTEN is dispensable for myeloid leukemia
cells in response to MAPK inhibitors, and PTEN regulates EGR1 expression and
contributes to the cytokine sensitivity in leukemia cells.
PMID- 29964150
TI - Relevance of N-terminal residues for amyloid-beta binding to platelet integrin
alphaIIbbeta3, integrin outside-in signaling and amyloid-beta fibril formation.
AB - A pathological hallmark of Alzheimer's disease (AD) is the aggregation of amyloid
beta peptides (Abeta) into fibrils, leading to deposits in cerebral parenchyma
and vessels known as cerebral amyloid angiopathy (CAA). Platelets are major
players of hemostasis but are also implicated in AD. Recently we provided strong
evidence for a direct contribution of platelets to AD pathology. We found that
monomeric Abeta40 binds through its RHDS sequence to integrin alphaIIbbeta3, and
promotes the formation of fibrillar Abeta aggregates by the secretion of
adenosine diphosphate (ADP) and the chaperone protein clusterin (CLU) from
platelets. Here we investigated the molecular mechanisms of Abeta binding to
integrin alphaIIbbeta3 by using Abeta11 and Abeta16 peptides. These peptides
include the RHDS binding motif important for integrin binding but lack the
central hydrophobic core and the C-terminal sequence of Abeta. We observed
platelet adhesion to truncated N-terminal Abeta11 and Abeta16 peptides that was
not mediated by integrin alphaIIbbeta3. Thus, no integrin outside-in signaling
and reduced CLU release was detected. Accordingly, platelet mediated Abeta fibril
formation was not observed. Taken together, the RHDS motif of Abeta is not
sufficient for Abeta binding to platelet integrin alphaIIbbeta3 and platelet
mediated Abeta fibril formation but requires other recognition or binding motifs
important for platelet mediated processes in CAA. Thus, increased understanding
of the molecular mechanisms of Abeta binding to platelet integrin alphaIIbbeta3
is important to understand the role of platelets in amyloid pathology.
PMID- 29964151
TI - Determination of mycotoxins by HPLC, LC-ESI-MS/MS, and MALDI-TOF MS in Fusarium
species-infected sugarcane.
AB - Mycotoxins are secondary metabolites of fungi that are damaging to both animals
and humans. Extensive contamination of foods and feeds with mycotoxins is an
important problem. Fumonisins, trichothecenes, zearalenone, and aflatoxins are
mycotoxins produced by Fusarium species and occur naturally in sugarcane and
cereal-based foods, threatening health and food security worldwide. Their
distribution in the contaminated material is of great interest for obtaining
insight into infection mechanisms and the potential for reducing contamination
during food processing. In this study, mycotoxins were evaluated by high
performance liquid chromatography, liquid chromatography-electrospray ionization
tandem mass spectrometry (LC-ESI-MS/MS), and matrix-assisted laser/desorption
ionization time of flight mass spectrometry (MALDI-TOF MS) of Fusarium species
infected sugarcane materials. A simple, sensitive, and reliable analytical method
was developed for rapidly detecting eight mycotoxins in Fusarium species:
fumonisin B1 and fumonisin B2, B-trichothecene mix (deoxynivalenol, nivalenol, 3
acetyl- deoxynivalenol, 15-acetyl-deoxynivalenol), zearalenone, and aflatoxin G1.
Analyses were carried out in multiple reaction monitoring mode using the two
primary product ions. The results generated by LC/MS and MALDI-TOF MS/MS revealed
various mechanisms regulating mycotoxins production, which may help to clarify
the roles of sensitive and selective compounds. The results demonstrate that this
procedure is suitable for simultaneous determination of mycotoxins in sugarcane
and can be performed in routine analysis in mycotoxin laboratories.
PMID- 29964153
TI - Cardiac Intensive Care Units: What Should be the Standard of Care?
AB - Since the creation of intensive care units (ICU) in the early 1960s, the central
question of how to operate and staff them has continued to be an ongoing
discussion. Early studies demonstrated decreased morality when staffing was
altered from remote providers to full-time on-site providers. In addition to the
shift towards full-time onsite providers, the structure of daily care has also
undergone significant paradigm changes. Several studies have revealed the
importance and benefit of multidisciplinary rounds with direct and open
communication of daily goals. Particularly for cardiac patients in shock, two
recent studies have provided hard data demonstrating a significant decrease in
mortality in ICUs with full-time onsite providers. This benefit was even more
pronounced for patients supported with extracorporeal membrane oxygenation. These
data support the practice of intensive care with (1) full-time onsite provider
staffing, (2) multidisciplinary rounds, and (3) a safe environment with open
communication between team members.
PMID- 29964152
TI - Role of autophagy in regulating the immune response of dendritic cells to
Talaromyces marneffei infection.
AB - Autophagy can regulate antimicrobial immunity. However, it is unknown whether
autophagy mediates the immune response of dendritic cells (DCs) to Talaromyces
marneffei (T. marneffei) infection. Therefore, to explore the relationship
between autophagy and multiplication of T. marneffei and investigate whether
ERK1/2 signaling pathway regulates activation of autophagy and TNF-alpha and IFN
gamma secretion by intracellular signaling mechanisms during T. marneffei
infection in human DCs. DCs were infected with T. marneffei for different times.
First, we found that T. marneffei induced activation of autophagy and ERK1/2 in
human DCs. Second, the inhibition of ERK1/2 suppressed activation of autophagy in
T. marneffei-infected human DCs. Third, the suppression of ERK1/2 and autophagy
decreased TNF-alpha and IFN-gamma production and increased the proliferation of
T. marneffei. These data suggest that ERK pathway plays vital regulatory roles in
activation of autophagy and subsequent cytokine production during T. marneffei
infection. Our data further indicate that autophagy is important in the
regulation of the DC immune response to T. marneffei infection, thereby extending
our understanding of host immune responses to the fungus.
PMID- 29964154
TI - Acid Sensing Ion Channel 1a (ASIC1a) Mediates Activity-induced Pain by Modulation
of Heteromeric ASIC Channel Kinetics.
AB - Chronic muscle pain is acutely worsened by exercise. Acid sensing ion channels
(ASIC) are heteromeric channels expressed in muscle sensory neurons that detect
decreases in pH. We have previously shown ASIC3 is important in activity-induced
hyperalgesia. However, ASICs form heteromers with ASIC1a being a key component in
sensory neurons. Therefore, we studied the role of ASIC1a in mice using
behavioral pharmacology and genetic deletion in a model of activity-induced
hyperalgesia. We found ASIC1a-/- mice developed mechanical hyperalgesia similar
to wild-type mice, but antagonism of ASIC1a, with psalmotoxin, prevented
development of mechanical hyperalgesia in wild-type mice, but not in ASIC1a-/-
mice. To explain this discrepancy, we then performed electrophysiology studies of
ASICs and examined the effects of psalmotoxin on ASIC heteromers. We expressed
ASIC1a, 2 and 3 heteromers or ASIC1 and 3 heteromers in CHO cells, and examined
the effects of psalmotoxin on pH sensitivity. Psalmotoxin significantly altered
the properties of ASIC hetomeric channels. Specifically, in ASIC1a/2/3
heteromers, psalmotoxin slowed the kinetics of desensitization, slowed the
recovery from desensitization, and inhibited pH-dependent steady-state
desensitization, but had no effect on pH-evoked current amplitudes. We found a
different pattern in ASIC1a/3 heteromers. There was a significant leftward shift
in the pH dose response of steady-state desensitization and decrease in pH-evoked
current amplitudes. These results suggest that blockade of ASIC1a modulates the
kinetics of heteromeric ASICs to prevent development of activity-induced
hyperalgesia. These data suggest ASIC1a is a key subunit in heteromeric ASICs and
may be a pharmacological target for treatment of musculoskeletal pain.
PMID- 29964155
TI - Impaired Neuronal Differentiation of Neural Stem Cells Lacking the Engrailed-2
Gene.
AB - The Engrailed-2 (En2) gene codes for a homeobox-containing transcription factor,
involved in midbrain-hindbrain embryonic development. In postnatal brain, En2 is
expressed in the ventral mesencephalon, cerebellum, hippocampus and neocortex.
Two single-nucleotide polymorphisms (SNPs) that are associated to autism spectrum
disorders (ASD) have been identified in the human EN2 gene. Accordingly, mice
lacking the En2 homeodomain (En2hd/hd, referred to as En2-/-) show molecular,
anatomical and behavioral "ASD-like" features. Among these, we previously showed
a partial loss of GABAergic interneurons in the En2-/- postnatal hippocampus and
neocortex, accompanied by a marked decrease of brain-derived neurotrophic factor
(BDNF) signaling, a crucial determinant of GABAergic differentiation. In order to
better investigate the role of En2 in GABAergic interneuron differentiation, we
generated and subsequently differentiated neural stem cells (NSCs) from basal
ganglia and neocortex of En2+/+ and En2-/- mouse embryos. Wild-type NSCs from
both basal ganglia and neocortex express En2, while mutant ones do not, as
expected. As compared to En2+/+ NSCs, En2-/- NSCs derived from basal ganglia show
impaired GABAergic differentiation accompanied by a reduced expression of the
BDNF receptor trkB. Conversely, En2-/- NSCs derived from the neocortex expressed
high levels of trkB and readily differentiated into neurons, as En2+/+ NSCs. Our
results suggest that En2 contributes to GABAergic neuron differentiation from
basal ganglia NSCs through a trkB-dependent BDNF signaling, thus providing a
possible explanation for the reduced number of GABAergic interneurons detected in
the En2-/- postnatal forebrain.
PMID- 29964156
TI - Genetic Modulation of HSPA1A Accelerates Kindling Progression and Exerts Pro
convulsant Effects.
AB - Strong evidence exists that Toll-like receptor (TLR)-mediated effects on
microglia functional states can promote ictogenesis and epileptogenesis. So far,
research has focused on the role of high-mobility group box protein 1 as an
activator of TLRs. However, the development of targeting strategies might need to
consider a role of additional receptor ligands. Considering the fact that heat
shock protein A1 (hsp70) has been confirmed as a TLR 2 and 4 ligand, we have
explored the consequences of its overexpression in a mouse kindling paradigm. The
genetic modulation enhanced seizure susceptibility with lowered seizure
thresholds prior to kindling. In contrast to wildtype (WT) mice, HSPA1A
transgenic (TG) mice exhibited generalized seizures very early during the
kindling paradigm. Along with an increased seizure severity, seizure duration
proved to be prolonged in TG mice during this phase. Toward the end of the
stimulation phase seizure parameters of WT mice reached comparable levels.
However, a difference between genotypes was still evident when comparing seizure
parameters during the post-kindling threshold determination. Surprisingly, HSPA1A
overexpression did not affect microglia activation in the hippocampus. In
conclusion, the findings demonstrate that hsp70 can exert pro-convulsant effects
promoting ictogenesis in naive animals. The pronounced impact on the response to
subsequent stimulations gives first evidence that genetic HSPA1A upregulation may
also contribute to epileptogenesis. Thus, strategies inhibiting hsp70 or its
expression might be of interest for prevention of seizures and epilepsy. However,
conclusions about a putative pro-epileptogenic effect of hsp70 require further
investigations in models with development of spontaneous recurrent seizures.
PMID- 29964157
TI - Preconception Paternal Stress in Rats Alters Brain and Behavior in Offspring.
AB - Whereas environmental challenges during gestation have been repeatedly shown to
alter offspring brain architecture and behavior, exploration examining the
consequences of paternal preconception experience on offspring outcome is
limited. The goal of this study was to examine the effects of preconception
paternal stress (PPS) on cerebral plasticity and behavior in the offspring.
Several behavioral assays were performed on offspring between postnatal days 33
(P33) and 101 (P101). Following behavioral testing, the brains were harvested and
dendritic morphology (dendritic complexity, length, and spine density) were
examined on cortical pyramidal cells in medial prefrontal cortex (mPFC), orbital
frontal cortex (OFC), parietal cortex (Par1), and the CA1 area of the
hippocampus. As anticipated, behavior was altered on both the activity box assay
and elevated plus maze and performance was impaired in the Whishaw tray reaching
task. Neuroanatomical measures revealed a heavier brain in stressed animals and
dendritic changes in all regions measured, the precise effect varying with the
measure and cerebral region. Thus, PPS impacted both behavior and neuronal
morphology of offspring. These effects likely have an epigenetic basis given that
in a parallel study of littermates of the current animals we found extensive
epigenetic changes at P21.
PMID- 29964158
TI - Hypoxia and myelination deficits in the developing brain.
AB - Myelination is a complex and orderly process during brain development that is
essential for normal motor, cognitive and sensory functions. Cellular and
molecular interactions between myelin-forming oligodendrocytes and axons are
required for normal myelination in the developing brain. Oligodendrocyte
progenitor cells (OPCs) proliferate and differentiate into mature myelin-forming
oligodendrocytes. In this connection, astrocytes and microglia are also involved
in survival and proliferation of OPCs. Hypoxic insults during the perinatal
period affect the normal development, differentiation and maturation of the OPCs
or cause their death resulting in impaired myelination. Several factors such as
augmented release of proinflammatory cytokines by activated microglia and
astrocytes, extracellular accumulation of excess glutamate and increased levels
of nitric oxide are some of the underlying factors for hypoxia induced damage to
the OPCs. Additionally, hypoxia also leads to down-regulation of several genes
involved in oligodendrocyte differentiation encoding proteolipid protein,
platelet-derived growth factor receptor and myelin-associated glycoprotein in the
developing brain. Furthermore, oligodendrocytes may also accumulate increased
amounts of iron in hypoxic conditions that triggers endoplasmic reticulum stress,
misfolding of proteins and generation of reactive oxygen species that ultimately
would lead to myelination deficits. More in-depth studies to elucidate the
pathophysiological mechanisms underlying the inability of oligodendrocytes to
myelinate the developing brain in hypoxic insults are desirable to develop new
therapeutic options or strategies for myelination deficits.
PMID- 29964159
TI - Fractal dimension analysis a supplementary mathematical method for bone defect
regeneration measurement.
AB - AIM OR PURPOSE: The geometry of a bone defect is very complex. Its shape is too
complicated to measure or compare with other bone defects using only traditional
measuring methods Traditional measuring techniques based on the histomorphometric
analysis of a bone specimen require supplementary measuring. For the fractal
dimension analysis (FDA) mathematic formulas are used to describe complicated and
chaotic shapes. The FDA offers a possibility of a comparison between complicated
and complex shapes such as a histological image of a bone defect. The aim of this
study was to evaluate the FDA of bone defects as a supplementary method for a
defect regeneration assessment. MATERIALS AND METHODS: For the purpose of this
study, microscopic photographs of bone specimens stained with hematoxylin and
eosin obtained during a block biopsy were used. The bone blocks used in this
study were obtained during a rat animal model study. Specimens were collected
from 36 Wistar rats where a cranial defect was created and augmented with five
different novel biomaterials and compared to the unfilled defect in the control
group. New bone formation in every specimen was histomorphometrically measured by
two independent operators and compared to FDA measurements. RESULTS: Both
traditional and FDA techniques have shown statistically significant differences
between bone formation in test groups compared to the control one; on the other
hand, no statistically significant difference was found between other groups. The
Pearson's r-test was conducted to measure the linear dependence (correlation)
between standard measurements and the FDA, and a positive linear correlation was
found -r=0.94. CONCLUSIONS: The FDA can be used as a supplementary method for
bone regeneration measurements.
PMID- 29964160
TI - "Hearts that strain": Distinguishing athlete's heart from hypertensive disease in
the echo lab and beyond.
AB - Individuals with hypertension that engage in regular exercise comprise a special
patient group that needs a careful approach to differentiate hypertensive cardiac
damage from physiologic cardiac adaptations. Echocardiography is the diagnostic
modality of choice in such cases. Hypertensive left ventricular hypertrophy is
expected to resemble isometric exercise-associated hypertrophy in some but not
all cases. On the other side, the hearts of regularly exercising individuals are
expected to be normal or present with a variable mix of increased end-diastolic
volume and increased wall thickness. It is therefore important to clearly
document the type, frequency and duration of exercise performed. Diastolic
dysfunction even without hypertrophy is often the first and only presentation in
hypertension. On the contrary, diastolic function in athletes may be enhanced in
order to maintain a stroke volume in high heart rates. Novel imaging techniques
such as global longitudinal strain are helpful to identify subclinical systolic
dysfunction that is inconsistent with athletic cardiac changes.
PMID- 29964162
TI - Monographic issue of pharmacological research on hypertension.
PMID- 29964161
TI - Human-based systems: Mechanistic NASH modelling just around the corner?
AB - Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by
excessive triglyceride accumulation in the liver accompanied by inflammation,
cell stress and apoptosis. It is the tipping point to the life-threatening stages
of non-alcoholic fatty liver disease (NAFLD). Despite the high prevalence of
NASH, up to five percent of the global population, there are currently no
approved drugs to treat this disease. Animal models, mostly based on specific
diets and genetic modifications, are often employed in anti-NASH drug
development. However, due to interspecies differences and artificial pathogenic
conditions, they do not represent the human situation accurately and are
inadequate for testing the efficacy and safety of potential new drugs. Human
based in vitro models provide a more legitimate representation of the human NASH
pathophysiology and can be used to investigate the dysregulation of cellular
functions associated with the disease. Also in silico methodologies and pathway
based approaches using human datasets, may contribute to a more accurate
representation of NASH, thereby facilitating the quest for new anti-NASH drugs.
In this review, we describe the molecular components of NASH and how human-based
tools can contribute to unraveling the pathogenesis of this disease and be used
in anti-NASH drug development. We also propose a roadmap for the development and
application of human-based approaches for future investigation of NASH.
PMID- 29964163
TI - Inhibiting constitutive neurogenesis compromises long-term social recognition
memory.
AB - Although the functional role for newborn neurons in neural circuits is still
matter of investigation, there is no doubt that neurogenesis modulates learning
and memory in rodents. In general, boosting neurogenesis before learning, using
genetic-target tools or drugs, improves hippocampus-dependent memories. However,
inhibiting neurogenesis may yield contradictory results depending on the type of
memory evaluated. Here we tested the hypothesis that inhibiting constitutive
neurogenesis would compromise social recognition memory (SRM). Male Swiss mice
were submitted to three distinct procedures to inhibit neurogenesis: (1) intra
cerebral infusion of Cystosine-beta-D-Arabinofuranoside (AraC); (2) intra
peritoneal injection of temozolomide (TMZ) and (3) cranial gamma irradiation. All
three methods decreased cell proliferation and neurogenesis in the dentate gyrus
of the dorsal (dDG) and ventral hippocampus (vDG), and the olfactory bulb (OB).
However, the percentage inhibition diverged between methods and brain regions.
Ara-C, TMZ and gamma irradiation impaired SRM, though only gamma irradiation did
not cause side effects on weight gain, locomotor activity and anxiety. Finally,
we examined the contribution of cell proliferation in vDG, dDG and OB to SRM. The
percent of inhibition in the dDG correlates with SRM, independently of the method
utilized. This correlation was observed for granular cell layer of OB and vDG,
only when the inhibition was induced by gamma irradiation. Animal's performance
was restrained by the inhibition of dDG cell proliferation, suggesting that cell
proliferation in the dDG has a greater contribution to SRM. Altogether, our
results demonstrate that SRM, similarly to other hippocampus-dependent memories,
has its formation impaired by reducing constitutive neurogenesis.
PMID- 29964164
TI - Cannabinoid agonist administration within the cerebellar cortex impairs motor
learning.
AB - Systemic administration of cannabinoid agonists impairs cerebellum-dependent
motor learning. The cannabinoid-induced impairment of motor learning has been
hypothesized to be due to disruption of Purkinje cell plasticity within the
cerebellar cortex. In the current study, we tested this hypothesis in rats with
localized microinfusions of cannabinoid agonists and antagonists into the
cerebellar cortex during eyeblink conditioning, a type of cerebellum-dependent
motor learning. Infusions of the cannabinoid agonists WIN55,212-2 or ACEA
directly into the eyeblink conditioning microzone of the cerebellar cortex
severely impaired acquisition of eyeblink conditioning, whereas the CB1R
antagonist SR141716A did not produce a significant impairment. Infusions of
WIN55,212-2 outside of the eyeblink conditioning microzone did not impair motor
learning, establishing anatomical specificity for the agonist effects. The motor
learning impairment caused by WIN55,212-2 and ACEA was rescued by SR141716A,
indicating that the learning deficit was produced through CB1Rs. The current
findings demonstrate that the effects of cannabinoid receptor agonists on motor
learning are localized to CB1Rs within a discrete microzone of the cerebellar
cortex.
PMID- 29964165
TI - Inputs to medullary respiratory neurons from a pontine subregion that controls
breathing frequency.
AB - Neurons in a subregion of the medial parabrachial (PB) complex control expiratory
duration (TE) and the inspiratory on-switch. To better understanding the
underlying mechanisms, this study aimed to determine the types of medullary
neurons in the rhythmogenic preBotzinger/ Botzinger Complex (preBotC/BotC) and
adjacent areas that receive synaptic inputs from the PB subregion and whether
these inputs are excitatory or inhibitory in nature. Highly localized electrical
stimuli in the PB subregion combined with multi-electrode recordings from
respiratory neurons and phrenic nerve activities were used to generate stimulus
to-spike event histograms to detect correlations in decerebrate, vagotomized dogs
during isocapnic hyperoxia. Short-time scale correlations were found in 237/442
or ~54% of the ventral respiratory column (VRC) neurons. Inhibition of E-neurons
was ~2.5X greater than for I-neurons, while Pre-I and I-neurons were excited.
These findings indicate that the control of TE and the inspiratory on-switch by
the PB subregion are mediated by a marked inhibition of BotC E-neurons combined
with an excitation of I-neurons, especially pre-I neurons.
PMID- 29964166
TI - Giant mycotic right coronary aneurism: A rare complication of Staphylococcus
aureus native valve endocarditis.
PMID- 29964167
TI - A single amino acid polymorphism in ABCC2 loop 1 is responsible for differential
toxicity of Bacillus thuringiensis Cry1Ac toxin in different Spodoptera
(Noctuidae) species.
AB - Bacillus thuringiensis Cry toxins exert their toxicity by forming membrane pores
after binding with larval midgut membrane proteins known as receptors. Spodoptera
litura and Spodoptera frugiperda belong to the same genus, but S. litura is
tolerant to Cry1Ac, while S. frugiperda is susceptible. The mechanism involved in
the differential toxicity of Cry1Ac to these insect species is not understood.
Amino acid sequences analysis of ABCC2, a well-recognized Cry1Ac receptor, from
both species showed high sequence identity. Hi5 insect cells expressing SfABCC2
from S. frugiperda were 65-fold more susceptible than those expressing the
SlABCC2 from S. litura. Substitution of fragments, point mutations and deletions
between the ABCC2 of the two species revealed that ABCC2 amino acid Q125 from
SfABCC2 or E125 from SlABCC2 was key factor for the differential Cry1Ac toxicity
to Hi5 cells expressing these receptors. Consistently with this, cells expressing
Helicoverpa armigera HaABCC2Q122-GFP, were more susceptible to Cry1Ac than cells
expressing HaABCC2E122-GFP mutant. Q125 or E125 is located in a predicted exposed
loop 1 region of ABCC2 indicating that this region could be important for Cry1Ac
binding. These findings identified a single amino acid residue located in loop 1
of ABCC2 transporter as responsible for the different levels of susceptibility to
Cry1Ac among various lepidopteran species.
PMID- 29964168
TI - Sodium butyrate attenuates diabetes-induced aortic endothelial dysfunction via
P300-mediated transcriptional activation of Nrf2.
AB - Oxidative stress and inflammation are major contributors to diabetes-induced
endothelial dysfunction which is the critical first step to the development of
diabetic macrovascular complications. Nuclear factor erythroid 2-related factor 2
(NRF2) plays a key role in combating diabetes-induced oxidative stress and
inflammation. Sodium butyrate (NaB) is an inhibitor of histone deacetylase (HDAC)
and an activator of NRF2. However, NaB's effect on diabetes-induced aortic injury
was unknown. It was also not known whether or to what extent NRF2 is required for
both self-defense and NaB's protection in the diabetic aorta. Additionally, the
mechanism by which NaB activates NRF2 was unclear. Therefore, C57BL/6 Nrf2
knockout (KO) and wild type (WT) mice were induced to diabetes by streptozotocin,
and were treated in the presence or absence of NaB, for 20 weeks. The KO diabetic
mice developed more severe aortic endothelial oxidative stress, inflammation and
dysfunction, as compared with the WT diabetic mice. NaB significantly attenuated
these effects in the WT, but not the KO, mice. In high glucose-treated aortic
endothelial cells, NaB elevated Nrf2 mRNA and protein without facilitating NRF2
nuclear translocation, an effect distinct from that of sulforaphane. NaB
inhibited HDAC activity, and increased occupancy of the transcription factor aryl
hydrocarbon receptor and the co-activator P300 at the Nrf2 gene promoter.
Further, the P300 inhibitor C646 completely abolished NaB's efficacies. Thus,
NRF2 is required for both self-defense and NaB's protection against diabetes
induced aortic endothelial dysfunction. Other findings suggest that P300 mediates
the transcriptional activation of Nrf2 by NaB.
PMID- 29964169
TI - Anthocyanins and their gut metabolites attenuate monocyte adhesion and
transendothelial migration through nutrigenomic mechanisms regulating endothelial
cell permeability.
AB - Cardioprotective effects of dietary anthocyanins are partly attributed to their
ability to maintain endothelial function. However, the underlying cellular and
molecular mechanisms of action are not fully understood. This study aimed to
evaluate the effect of anthocyanins and their gut metabolites, at physiologically
relevant conditions, on endothelial cell (EC) function and decipher the
underlying molecular mechanisms of action using integrated omics approaches.
Primary EC were treated with a mixture of 0.1 MUM cyanidin-3-arabinoside, 0.1 MUM
cyanidin-3-galactoside, 0.1 MUM cyanidin-3-glucoside, 0.1 MUM delphinidin-3
glucoside, 0.1 MUM peonidin-3-glucoside and 0.5 MUM 4-hydroxybenzaldehyde for 3 h
or a mixture of gut metabolites: 0.2 MUM protocatechuic, 2 MUM vanillic, 1 MUM
ferulic and 2 MUM hippuric acids for 18 h. Also, successive exposure of EC to
both mixtures was performed to mimic anthocyanin pharmacokinetics following their
intake. Inflammatory stress was induced using TNFalpha and monocytes added to
assess adhesion and transmigration. Effects of these mixtures on gene, miRNA
expression and their potential interaction with cell signalling were
investigated. Anthocyanins and their gut metabolites significantly reduced
monocyte adhesion and transendothelial migration. Gene expression analysis, using
macroarrays, showed that tested compounds modulated the expression of genes
involved in cell-cell adhesion, cytoskeleton organisation or focal adhesion.
Bioinformatics analyses of gene expression data identified potential
transcription factors involved in the observed nutrigenomic effects and
signalling proteins regulating their activity. Molecular docking revealed cell
signalling proteins to which these bioactives may bind to and potentially affect
their activity and the activation of downstream signalling, effects that were in
agreement with the results of Western blot analyses. Microarray analysis showed
that anthocyanins and their gut metabolites affected miRNA expression in EC,
especially those involved in regulation of EC permeability, contributing to the
observed changes in EC function. Integration of these results revealed
endothelial-protective properties of anthocyanins and their gut metabolites and
deciphered new underlying multi-target and multi-layered mode of action.
PMID- 29964170
TI - Impaired glutathione-related antioxidant defenses in the arterial tissue of
diabetic patients.
AB - We studied the specific enzymatic activities of selenium-dependent (GSH-Px) and
independent (GST-Px) glutathione peroxidase, glutathione reductase (GSSG-Red),
and glutathione S-transferase (GST) in internal mammary arteries (IMArt)
specimens obtained during coronary artery bypass surgery in 18 patients with type
2 diabetes mellitus as compared to 18 non-diabetic controls; vascular lipid
peroxidation, namely fluorescent damage products of lipid peroxidation (FDPL) as
4-hydroxynonenal-related oxidative stress indicators, was also studied. Moreover,
in other 16 diabetic patients and 16 controls, total glutathione (TGlut) was
determined in IMArt specimens specifically homogenized in sulfosalycilic acid to
prevent vascular GSH depletion. The activities of GSH-Px, GSSG-Red, and GST were
significantly lower, and FDPL levels higher, in the arterial tissue of diabetic
patients than in that of controls; GST-Px was undetectable. Such enzymatic
activities were inversely correlated with vascular lipid peroxidation,
highlighting their antioxidant role in the arterial tissue, as were HbA1c and
FDPL levels with the enzymatic activities, suggesting that glycation, oxidant
species and lipoperoxidation aldehydes may be involved in glutathione-related
enzyme inactivation. Further, in the diabetic patients HbA1c was correlated
directly with lipid peroxidation but inversely with TGlut of the arterial tissue.
In the patients considered for vascular enzymatic activities and FDPL assay, 3/4
vessel coronary artery disease (CAD) as expression of atherosclerosis severity
was present in 9 diabetic patients and in 3 controls. Notably, vascular
glutathione-related enzymatic activities were significantly lower, and FDPL
levels higher, in the 9 diabetic patients with 3/4-vessel CAD than in the 9
without, as well as in the total of 12 patients with 3/4-vessel CAD than in the
total of 24 patients without. Moreover, vascular TGlut content was significantly
lower in the diabetic than in the control patients. Three/4-vessel CAD was
present in 6 diabetic patients and in 2 controls considered for determination of
vascular Tglut content, which was significantly lower in the diabetic patients
with 3/4-vessel CAD than in those without, as well in the total of 8 patients
with 3/4-vessel CAD than in the total of 24 patients without. Thus, weakened
glutathione-related antioxidant capacity and oxidative stress of the arterial
tissue are associated with the severity of atherosclerosis. In conclusion,
impaired glutathione-related antioxidant defenses of the arterial tissue occur in
diabetic patients, eventually favoring vascular oxidative stress and the severity
of atherosclerosis.
PMID- 29964172
TI - Exploring the role of polymeric conjugates toward anti-cancer drug delivery:
Current trends and future projections.
AB - Utilizing the diverse features of biocompatible polymers to target drugs into the
tumor/s has been a research hotspot since last decade. Such polymeric conjugates
of anti-cancer drugs have proven their potential in providing sustained release
of drugs with reduced systemic toxicity and improved tumor retention. Polymers
like polyethylene glycol (PEG), N-(2-Hydroxypropyl) methacrylamide (HPMA),
Polylactic-co-glycolic acid (PLGA), Polyamidoamine (PAMAM), and others remain
exploited for their specific as well as shared characteristics in the rational
delivery of anti-cancer agents. Variable nano size, attachment with tumor
specific proteins, responsiveness to stimuli and ability to deliver a wide range
of molecules like drugs, antibodies and peptides are some of the achievements of
polymeric nano-conjugates so far. Many such conjugates have shown potential
clinically which has attracted the researchers and promoted further advancements
of the technique. Apart from achievements the polymeric conjugates suffer from
shortcomings like poor drug loading and chances of potential chronic-systemic
toxicities. The review highlights key findings of research in recent time and
advancements taking place in the field of polymeric conjugates of anti-cancer
drugs along with the limitations. We have also emphasized on newer and relatively
less explored applications of tumor-targeted polymeric conjugates which can add
new dimensions to this technique.
PMID- 29964173
TI - Oropharyngeal administration of silica in Swiss mice: A robust and reproducible
model of occupational pulmonary fibrosis.
AB - Pulmonary fibrosis (PF) is a lethal end stage of interstitial lung disease with
increasing prevalence. The disease burden of PF has seen a sharp surge in the
past two decades owing to entry of heavy amount of particulate matter due to
industrialization and urbanization. In this work, we developed an oropharyngeal
aspiration model of silica (1.5 mg/mice) induced pulmonary fibrosis as a
homogeneous, reproducible, simple and alternative strategy in Swiss albino mice.
Various BALF (protein, albumin, cell count), biochemical parameters (MDA, GSH,
hydroxyproline), cytokines (IL-1beta, IL-6, TNF-alpha and TGF-beta1),
histological (H&E and PSR staining) and protein expression (N-cadherin, vimentin,
alpha-SMA, CTGF, collagen-1) studies were conducted to validate the model.
Oropharyngeal administration of silica in Swiss mice produced significantly
changes in lung morphology with statistically higher lung weights compared to
normal control animals. The silica treated mice showed profoundly elevated BALF
soluble and cytological parameters and enhanced oxidative and nitrosative stress
in lungs. The levels of hydroxyproline were increased by 2.6 fold in the silica
treated mice. The expression of pro-inflammatory cytokines were profoundly
increased in silica treated mice. The histology and PSR staining indicated
increased inflammatory infiltration and staggering fibrosis in silica treated
group. In addition, the expression of EMT markers (N-cadherin, vimentin, alpha
SMA and CTGF) were significantly increased indicating their role in silica
induced pulmonary fibrosis. Our work clearly demonstrates the superiority of
stress free oropharyngeal instillation of silica with dose reduction over the
conventional invasive and non-homogeneous intratracheal route.
PMID- 29964171
TI - Oxidized phospholipid signaling in traumatic brain injury.
AB - Oxidative stress is a major contributor to secondary injury signaling cascades
following traumatic brain injury (TBI). The role of lipid peroxidation in the
pathophysiology of a traumatic insult to neural tissue is increasingly
recognized. As the methods to quantify lipid peroxidation have gradually
improved, so has the understanding of mechanistic details of lipid peroxidation
and related signaling events in the injury pathogenesis. While free-radical
mediated, non-enzymatic lipid peroxidation has long been studied, recent advances
in redox lipidomics have demonstrated the significant contribution of enzymatic
lipid peroxidation to TBI pathogenesis. Complex interactions between
inflammation, phospholipid peroxidation, and hydrolysis define the engagement of
different cell death programs and the severity of injury and outcome. This review
focuses on enzymatic phospholipid peroxidation after TBI, including the mechanism
of production, signaling roles in secondary injury pathology, and temporal course
of production with respect to inflammatory response. In light of the newly
identified phospholipid oxidation mechanisms, we also discuss possible
therapeutic targets to improve neurocognitive outcome after TBI. Finally, we
discuss current limitations in identifying oxidized phospholipids and possible
methodologic improvements that can offer a deeper insight into the region
specific distribution and subcellular localization of phospholipid oxidation
after TBI.
PMID- 29964174
TI - Mishandling of pMDI and DPI inhalers in asthma and COPD - Repetitive and non
repetitive errors.
AB - BACKGROUND: Pharmacological treatment of asthma and chronic obstructive pulmonary
disease (COPD) is based mainly on inhaled medications. There is a continuous need
to examine and train patients in their inhalation technique. The objective of the
presented study is to determine whether the errors which patients made during
inhalations are repetitive, and therefore easier to eradicate, or rather
accidental, hence require more attention and effort from the health care
professionals. METHODS: It was a prospective, cohort study which included adults
with asthma or COPD, who have used at least one inhaler daily on a regular basis.
Inhalation technique was evaluated twice in a six months interval basing on a
list of the most common errors in the inhalation technique. There was no training
of inhalation skills between visits. RESULTS: There were 92 patients (46
asthmatics, 46 with COPD; median age 66 years, median duration of the disease 10
years) included into the analysis. 92% of patients made at least one error during
their inhalation. Among pMDI users the most common device mishandlings were: no
or too short breath-holding after inhalation (60% of the patients during the
first visit; 50% during the 2nd), too rapid and too forceful inhalation (52%;
61%) and lack of exhalation before the use of the medicine (48%; 43%). Among the
DPI users, the most numerous errors were: no or too short (less than 3 s) breath
holding after inhalation (62%; 55%) and slow and not forceful enough inhalation
(38%; 36%). When comparing the mishandlings in the inhalation technique conducted
during the first and second visit the majority of the errors conducted by the
patients were repetitive. However, some errors such as too early termination of
inhalation (p = 0.016), inhalation through the nose during actuation (p = 0.002)
among pMDI users and lack of expiration before inhalation (p = 0.027) among DPI
users, were non-permanent. CONCLUSIONS: Improper inhalation technique is very
common and the majority of errors made in inhalation technique are repetitive.
This emphasizes the role of an ongoing verification and training of a proper
inhalation technique in all patients that are regularly treated with inhalers.
PMID- 29964176
TI - Optimized CRISPR-Cpf1 system for genome editing in zebrafish.
AB - The impact of the CRISPR-Cas biotechnological systems has recently broadened the
genome editing toolbox available to different model organisms further with the
addition of new efficient RNA-guided endonucleases. We have recently optimized
CRISPR-Cpf1 (renamed Cas12a) system in zebrafish. We showed that (i) in the
absence of Cpf1 protein, crRNAs are unstable and degraded in vivo, and CRISPR
Cpf1 RNP complexes efficiently mutagenize the zebrafish genome; and (ii)
temperature modulates Cpf1 activity especially affecting AsCpf1, which
experiences a reduced performance below 37 degrees C. Here, we describe a step
by-step protocol on how to easily design and generate crRNAs in vitro, purify
recombinant Cpf1 proteins, and assemble ribonucleoprotein complexes to carry out
efficient mutagenesis in zebrafish in a constitutive and temperature-controlled
manner. Finally, we explain how to induce Cpf1-mediated homology-directed repair
using single-stranded DNA oligonucleotides. In summary, this protocol includes
the steps to efficiently modify the zebrafish genome and other ectothermic
organisms using the CRISPR-Cpf1 system.
PMID- 29964175
TI - Practical aspects of high-pressure NMR spectroscopy and its applications in
protein biophysics and structural biology.
AB - Pressure and temperature are the two fundamental variables of thermodynamics.
Temperature and chemical perturbation are central experimental tools for the
exploration of macromolecular structure and dynamics. Though it has long been
recognized that hydrostatic pressure offers a complementary and often unique view
of macromolecular structure, stability and dynamics, it has not been employed
nearly as much. For solution NMR applications the limited use of high-pressure is
undoubtedly traced to difficulties of employing pressure in the context of modern
multinuclear and multidimensional NMR. Limitations in pressure tolerant NMR
sample cells have been overcome and enable detailed studies of macromolecular
energy landscapes, hydration, dynamics and function. Here we review the practical
considerations for studies of biological macromolecules at elevated pressure,
with a particular emphasis on applications in protein biophysics and structural
biology.
PMID- 29964177
TI - Two new polyketides from the roots of Stemona tuberosa.
AB - Two polyketides, stemonones A (1) and B (2) with new skeletons, were isolated
from the roots of Stemona tuberosa. Their absolute structures were fully
characterized by comprehensive spectroscopic analyses and comparison of
experimental electronic circular dichroism (ECD) spectra with calculated ones.
The plausible biosynthetic pathways for 1 and 2 were also proposed. Anti
inflammatory assay confirmed that the two compounds showed moderate inhibitory
effects on beta-glucuronidase release in rat polymorphonuclear leukocytes (PMNs)
induced by platelet-activating factor.
PMID- 29964178
TI - Ultrasound-guided percutaneous microwave ablation for subserosal uterine
fibroids.
AB - STUDY OBJECTIVE: To prospectively evaluate the clinical effectiveness and safety
of ultrasound-guided percutaneous microwave ablation for symptomatic subserosal
uterine fibroids. DESIGN: Prospective observational study (Canadian Task Force II
1). SETTING: A teaching hospital (Department of Interventional Ultrasound,
General Hospital of Chinese PLA, Beijing, China). PATIENTS: Sixty-nine patients
with symptomatic subserosal uterine fibroid. And the numbers of patients who
failed to show up for follow-up at 3, 6 and 12 months was after therapy were 21,
34 and 35, respectively. INTERVENTIONS: All the patients underwent ultrasound
guided percutaneous microwave ablation. MEASUREMENTS AND MAIN RESULTS: The
efficacy was evaluated by the mean fibroid volume shrinkage rate and changes in
Uterine Fibroid Symptom and Quality of Life Questionnaire scores at 3, 6 and 12
months after therapy. Treatment safety was evaluated using the Society of
Interventional Radiology Practice Guidelines. Mean patient age was 40.3 +/- 4.9
years (range, 26-49 y). Average fibroid volume before ablation was 221.74 +/-
153.18 cm3; at 3, 6 and 12 months after therapy, it had decreased to 87.24 +/-
45.93 cm3 (P < .001), 46.68 +/- 24.7 cm3 (P < .001) and 38.05 +/- 24.93 cm3 (P <
.001), respectively. Between pre-treatment and 3-month follow-up, the symptom
severity score decreased from 34.53 +/- 3.83 to 12.74 +/- 3.07 (P <.001) and the
health-related quality of life score increased from 45.25 +/- 10.97 to 78.48 +/-
11.39 (P <.001). Both scores remained stable at the 6- and 12-month follow-up
time points. No permanent injury or fatal complications were seen in this study.
CONCLUSION: Ultrasound-guided percutaneous microwave ablation of subserosal
uterine fibroids is a promising treatment method, while further studies with
large sample size and a control group are needed. Clinical trial registry name:
Chinese Clinical Trial Registry, URL: http://www.chictr.org.cn/, the registration
number: ChiCTR-TRC-10001119, date of trial registration: 06/01/2010.
PMID- 29964179
TI - Mesh Exposure After Robot-Assisted Laparoscopic Pelvic Floor Surgery: A
Prospective Cohort Study.
AB - STUDY OBJECTIVE: To prospectively evaluate the mesh exposure rate after robot
assisted laparoscopic pelvic floor surgery for the treatment of female pelvic
organ prolapse (POP) in a large cohort. DESIGN: Prospective observational cohort
study (Canadian Task Force classification II-2). SETTING: Two large teaching
hospitals with a tertiary referral function for pelvic floor disorders. PATIENTS:
Patients with symptomatic POP and simplified POP quantification (S-POP) stage
>=2. Patients with a history of mesh repair or concomitant insertion of a tension
free vaginal tape were excluded. INTERVENTIONS: Robot-assisted laparoscopic
sacrocolpopexy or robot-assisted laparoscopic supracervical hysterectomy with a
sacrocervicopexy. MEASUREMENTS AND MAIN RESULTS: A blinded vaginal examination
with the aid of a transparent speculum was performed to look for mesh-related
complications. Mesh exposures were described following the International
Urogynecological Association/International Continence Society classification
system. One hundred and ninety-two patients were included, of whom 166 (86.5%)
were seen for follow-up examination. The median duration of follow-up was 15.7
months (range, 8.2-44.4 months). Two vaginal mesh exposures (1.2%) were detected,
both of which were treated in the outpatient clinic. One patient without any
complaints had a suture exposure, which was removed in the outpatient clinic.
CONCLUSION: The safety of the use of mesh in pelvic floor surgery is a matter of
debate owing to the occurrence of mesh-related complications. Based on the
current literature, mesh-related complications seem to be lower in transabdominal
mesh surgery than in transvaginal mesh surgery. In this study, a low mesh
exposure rate was observed in robot-assisted abdominal pelvic floor surgery for
POP.
PMID- 29964180
TI - The implants used for intramedullary fixation of distal fibula fractures: A
review of literature.
AB - BACKGROUND: Ankle fractures are amongst the most common surgically treated
musculoskeletal injuries. Intramedullary (IM) fixation of the lateral malleolus
had been attempted as early as the 1990s. In recent years, dedicated implants
have emerged. This review evaluates the design characteristics of the technology
used to perform IM fixation of distal fibular fractures. MATERIALS AND METHODS: A
search of electronic databases was performed. Medical subject headings (MeSH) and
free-text terms were used to optimise search sensitivity and specificity.
RESULTS: We identified 10 different surgical technologies for IM fixation of
lateral malleolar fractures reported across 12 articles, including both
improvised and custom-designed Orthopaedic implants. Most implants were inserted
through percutaneous surgical techniques. CONCLUSION: Advances in technology have
improved the feasibility of intramedullary fixation as a treatment option for
lateral malleolus fractures. The implants we reviewed had very diverse
morphological and mechanical properties. Intra-medullary fixation may outperform
extra-medullary fixation of the lateral malleolus, particularly in patients at
high risk of soft tissue complications. Robust scientific evidence is awaited.
LEVEL OF EVIDENCE: Level IV evidence.
PMID- 29964182
TI - Long-term administration of pDC stimulative lactic acid bacteria, Lactococcus
lactis strain Plasma, prevents immune-senescence and decelerates individual
senescence.
AB - Aging is accompanied by the decline in immune function, resulting in increasing
susceptibility to infectious diseases and tumorigenesis. In our previous reports,
we showed that Lactococcus lactis subsp. lactis strain Plasma (LC-Plasma)
stimulated plasmacytoid dendritic cells (pDCs), which play an important role in
viral infection, and oral administration of LC-Plasma showed prophylactic effects
against viral infection both in mice and humans. However, the effects of long
term administration of LC-Plasma are not known. In this study, we investigated
the effect of long-term oral administration of LC-Plasma on IFN-alpha induction
activity and individual senescence in the senescence-accelerated mice strains
Prone 1 (SAMP1) and Prone 10 (SAMP10). LC-Plasma administration promoted IFN
alpha induction activity and increased the naive T cell ratio in SAMP1 mice. In
SAMP10 mice, in addition to preventing a decrease in the naive T cell ratio,
aging-associated skin thinning was suppressed histologically and the expression
of representative tight junction genes, such as Claudin-1 and Zo-1, was
increased. Furthermore, age-related muscle weight loss tended to be suppressed in
the LC-Plasma group and expression of the muscle degeneration gene FoxO-1 was
significantly suppressed. Related to these phenotypes, the senescence score in
the LC-Plasma group was significantly decreased at 47 weeks of age compared with
that in the control group. Taken together, long-term oral administration of LC
Plasma could prevent immune-senescence and other senescence phenotypes at the
organ level. Therefore, LC-Plasma is suggested to be a useful functional food
material for decelerating individual senescence.
PMID- 29964181
TI - Mapping genes for drug chronotherapy.
AB - Genome-wide association studies have been increasingly used to map and
characterize genes that contribute to interindividual variation in drug response.
Some studies have integrated the pharmacokinetic (PK) and pharmacodynamic (PD)
processes of drug reactions into association mapping, gleaning new insight into
how genes determine the dynamic relationship of drug effect and drug dose. Here,
we present an evolutionary framework by which two distinct concepts,
chronopharmacodynamics and heterochrony (describing variation in the timing and
rate of developmental events), are married to comprehend the pharmacogenetic
architecture of drug response. The resulting new concept,
heterochronopharmacodynamics (HCPD), can better interpret how genes influence
drug efficacy and drug toxicity according to the circadian rhythm of the body and
changes in drug concentration.
PMID- 29964183
TI - Investigating and reducing the effects of confounding factors for robust T1 and
T2 mapping with cardiac MR fingerprinting.
AB - This study aims to improve the accuracy and consistency of T1 and T2 measurements
using cardiac MR Fingerprinting (cMRF) by investigating and accounting for the
effects of confounding factors including slice profile, inversion and T2
preparation pulse efficiency, and B1+. The goal is to understand how measurements
with different pulse sequences are affected by these factors. This can be used to
determine which factors must be taken into account for accurate measurements, and
which may be mitigated by the selection of an appropriate pulse sequence.
Simulations were performed using a numerical cardiac phantom to assess the
accuracy of over 600 cMRF sequences with different flip angles, TRs, and
preparation pulses. A subset of sequences, including one with the lowest errors
in T1 and T2 maps, was used in subsequent analyses. Errors due to non-ideal slice
profile, preparation pulse efficiency, and B1+ were quantified in Bloch
simulations. Corrections for these effects were included in the dictionary
generation and demonstrated in phantom and in vivo cardiac imaging at 3 T.
Neglecting to model slice profile and preparation pulse efficiency led to
underestimated T1 and overestimated T2 for most cMRF sequences. Sequences with
smaller maximum flip angles were less affected by slice profile and B1+.
Simulating all corrections in the dictionary improved the accuracy of T1 and T2
phantom measurements, regardless of acquisition pattern. More consistent
myocardial T1 and T2 values were measured using different sequences after
corrections. Based on these results, a pulse sequence which is minimally affected
by confounding factors can be selected, and the appropriate residual corrections
included for robust T1 and T2 mapping.
PMID- 29964184
TI - Prospective gating control for highly efficient cardio-respiratory synchronised
short and constant TR MRI in the mouse.
AB - PURPOSE: Cardiac and respiratory motion derived image artefacts are reduced when
data are acquired with cardiac and respiratory synchronisation. Where steady
state imaging techniques are required in small animals, synchronisation is most
commonly performed using retrospective gating techniques but these invoke an
inherent time penalty. This paper reports the development of prospective gating
techniques for cardiac and respiratory motion desensitised MRI with significantly
reduced minimum scan time compared to retrospective gating. METHODS: Prospective
gating incorporating the automatic reacquisition of data corrupted by motion at
the entry to each breath was implemented in short TR 3D spoiled gradient echo
imaging. Motion sensitivity was examined over the whole mouse body for scans
performed without gating, with respiratory gating, and with cardio-respiratory
gating. The gating methods were performed with and without automatic
reacquisition of motion corrupted data immediately after completion of the same
breath. Prospective cardio-respiratory gating, with acquisition of 64 k-space
lines per cardiac R-wave, was used to enable whole body DCE-MRI in the mouse.
RESULTS: Prospective cardio-respiratory gating enabled high fidelity steady state
imaging of physiologically mobile organs such as the heart and lung. The
automatic reacquisition of data corrupted by motion at the entry to each breath
minimised respiratory motion artefact and enabled a highly efficient data capture
that was adaptive to changes in the inter-breath interval. Prospective cardio
respiratory gating control enabled DCE-MRI to be performed over the whole mouse
body with the acquisition of successive image volumes every 12-15 s at 422 MUm
isotropic resolution. CONCLUSIONS: Highly efficient cardio-respiratory motion
desensitised steady state MRI can be performed in small animals with prospective
synchronisation, centre-out phase-encode ordering, and the automatic
reacquisition of data corrupted by motion at the entry to each breath. The method
presented is robust against spontaneous changes in the breathing rate. Steady
state imaging with prospective cardio-respiratory gating is much more efficient
than with retrospective gating, and enables the examination of rapidly changing
systems such as those found when using DCE-MRI.
PMID- 29964186
TI - Evidence for distinct levels of neural adaptation to both coherent and
incoherently moving visual surfaces in visual area hMT.
AB - Visual adaptation describes the processes by which the visual system alters its
operating properties in response to changes in the environment. It is one of the
mechanisms controlling visual perceptual bistability - when two perceptual
solutions are available - by controlling the duration of each percept. Moving
plaids are an example of such ambiguity. They can be perceived as two surfaces
sliding incoherently over each other or as a single coherent surface. Here, we
investigated, using fMRI, whether activity in the human motion complex (hMT+), a
region tightly related to the perceptual integration of visual motion, is
modulated by distinct forms of visual adaptation to coherent or incoherent
perception of moving plaids. Our hypothesis is that exposure to global coherent
or incoherent moving stimuli leads to different levels of measurable adaptation,
reflected in hMT+ activity. We found that the strength of the measured visual
adaptation effect depended on whether subjects integrated (coherent percept) or
segregated (incoherent percept) surface motion signals. Visual motion adaptation
was significant both for coherent motion and globally incoherent surface motion.
Although not as strong as to the coherent percept, visual adaptation due to the
incoherent percept also affects hMT+. This shows that adaptation can contribute
to regulate percept duration during visual bistability, with distinct weights,
depending on the type of percept. Our findings suggest a link between bistability
and adaptation mechanisms, both due to coherent and incoherent motion percepts,
but in an asymmetric manner. These asymmetric adaptation weights have strong
implications in models of perceptual decision and may explain asymmetry of
perceptual interpretation periods.
PMID- 29964185
TI - Reproducibility of corticokinematic coherence.
AB - Corticokinematic coherence (CKC) between limb kinematics and
magnetoencephalographic (MEG) signals reflects cortical processing of
proprioceptive afference. However, it is unclear whether strength of CKC is
reproducible across measurement sessions. We thus examined reproducibility of CKC
in a follow-up study. Thirteen healthy right-handed volunteers (7 females, 21.7
+/- 4.3 yrs) were measured using MEG in two separate sessions 12.6 +/- 1.3 months
apart. The participant was seated and relaxed while his/her dominant or non
dominant index finger was continuously moved at 3 Hz (4 min for each hand) using
a pneumatic movement actuator. Finger kinematics were recorded with a 3-axis
accelerometer. Coherence was computed between finger acceleration and MEG
signals. CKC strength was defined as the peak coherence value at 3 Hz form a
single sensor among 40 pre-selected Rolandic gradiometers contralateral to the
movement. Pneumatic movement actuator provided stable proprioceptive stimuli and
significant CKC responses peaking at the contralateral Rolandic sensors. In the
group level, CKC strength did not differ between the sessions in dominant (Day-1
0.40 +/- 0.19 vs. Day-2 0.41 +/- 0.17) or non-dominant (0.35 +/- 0.16 vs. 0.36 +/
0.17) hand, nor between the hands. Intraclass-correlation coefficient (ICC)
values indicated excellent inter-session reproducibility for CKC strength for
both dominant (0.86) and non-dominant (0.97) hand. However, some participants
showed pronounced inter-session variability in CKC strength, but only for the
dominant hand. CKC is a promising tool to study proprioception in long-term
longitudinal studies in the group level to follow, e.g., integrity of cortical
proprioceptive processing with motor functions after stroke.
PMID- 29964187
TI - Variational Bayesian inversion for hierarchical unsupervised generative embedding
(HUGE).
AB - A recently introduced hierarchical generative model unified the inference of
effective connectivity in individual subjects and the unsupervised identification
of subgroups defined by connectivity patterns. This hierarchical unsupervised
generative embedding (HUGE) approach combined a hierarchical formulation of
dynamic causal modelling (DCM) for fMRI with Gaussian mixture models and relied
on Markov chain Monte Carlo (MCMC) sampling for inference. While well suited for
the inversion of complex hierarchical models, MCMC-based sampling suffers from a
computational burden that is prohibitive for many applications. To address this
problem, this paper derives an efficient variational Bayesian (VB) inversion
scheme for HUGE that simultaneously provides approximations to the posterior
distribution over model parameters and to the log model evidence. The face
validity of the VB scheme was tested using two synthetic fMRI datasets with known
ground truth. Additionally, an empirical fMRI dataset of stroke patients and
healthy controls was used to evaluate the practical utility of the method in
application to real-world problems. Our analyses demonstrate good performance of
our VB scheme, with a marked speed-up of model inversion by two orders of
magnitude compared to MCMC, while maintaining a similar level of accuracy.
Notably, additional acceleration would be possible if parallel computing
techniques were applied. Generally, our VB implementation of HUGE is fast enough
to support multi-start procedures for whole-group analyses, a useful strategy to
ameliorate problems with local extrema. HUGE thus represents a potentially useful
practical solution for an important problem in clinical neuromodeling and
computational psychiatry, i.e., the unsupervised detection of subgroups in
heterogeneous populations that are defined by effective connectivity.
PMID- 29964188
TI - Meaningful inhibition: Exploring the role of meaning and modality in response
inhibition.
AB - We frequently guide our decisions about when and how to act based on the meanings
of perceptual inputs: we might avoid treading on a flower, but not on a leaf.
However, most research on response inhibition has used simple perceptual stimuli
devoid of meaning. In two Go/No-Go experiments, we examined whether the neural
mechanisms supporting response inhibition are influenced by the relevance of
meaning to the decision, and by presentation modality (whether concepts were
presented as words or images). In an on-line fMRI experiment, we found common
regions for response inhibition across perceptual and conceptual decisions. These
included the bilateral intraparietal sulcus and the right inferior frontal
sulcus, whose neural responses have been linked to diverse cognitive demands in
previous studies. In addition, we identified a cluster in ventral lateral
occipital cortex that was sensitive to the modality of input, with a stronger
response to No-Go than Go trials for meaningful images, compared to words with
the same semantic content. In a second experiment, using resting-state fMRI, we
explored how individual variation in the intrinsic connectivity of these
activated regions related to variation in behavioural performance. Participants
who showed stronger connectivity between common inhibition regions and limbic
areas in medial temporal and subgenual anterior cingulate cortex were better at
inhibition when this was driven by the meaning of the items. In addition, regions
with a specific role in picture inhibition were more connected to a cluster in
the thalamus/caudate for participants who were better at performing the picture
task outside of the scanner. Together these studies indicate that the capacity to
appropriately withhold action depends on interactions between common control
regions, which are important across multiple types of input and decision, and
other brain regions linked to specific inputs (i.e., visual features) or
representations (e.g., memory).
PMID- 29964189
TI - In vivo manganese tract tracing of frontal eye fields in rhesus macaques with
ultra-high field MRI: Comparison with DWI tractography.
AB - The saccadic eye movement system has emerged as a valuable model for studying
neural circuitry related to flexible control of behavior. Although connections of
the saccadic circuitry are well documented via histochemical tracers, these
methods require fixed tissue and thus cannot provide longitudinal assessments of
connectivity. To circumvent this, diffusion weighted imaging (DWI) is often used
as a proxy for connectivity in vivo, allowing for the tracing of connections
longitudinally and noninvasively. DWI, however, has certain limitations in its
ability to estimate the paths of fiber tracts. Here, we demonstrate the use of
manganese, in an animal model, as an MRI-based in vivo labeling technique for
saccadic circuitry that allows for direct tract tracing without the need to
sacrifice the animal. Manganese is a strong paramagnetic contrast agent used for
T1-relaxation enhancement in MRI. Here, we locally injected MnCl2 into the
frontal eye fields (FEF), a key saccadic node, of two male rhesus macaques and
collected ultra-high field MRI data at 7 T (T1, DWI). The results demonstrate
that MnCl2-traced FEF connections parallel those established by histochemical
tracing (albeit at a lower spatial resolution) and suggest that DWI
underestimates FEF connectivity, likely due to crossing fibers and small tract
size. These results highlight the lack of DWI sensitivity for tracing subcortical
FEF fibers, but also suggest MnCl2-based tracing as a powerful alternative for
assessing these connections in vivo.
PMID- 29964190
TI - Reproducibility of importance extraction methods in neural network based fMRI
classification.
AB - Recent advances in machine learning allow faster training, improved performance
and increased interpretability of classification techniques. Consequently, their
application in neuroscience is rapidly increasing. While classification
approaches have proved useful in functional magnetic resonance imaging (fMRI)
studies, there are concerns regarding extraction, reproducibility and
visualization of brain regions that contribute most significantly to the
classification. We addressed these issues using an fMRI classification scheme
based on neural networks and compared a set of methods for extraction of category
related voxel importances in three simulated and two empirical datasets. The
simulation data revealed that the proposed scheme successfully detects spatially
distributed and overlapping activation patterns upon successful classification.
Application of the proposed classification scheme to two previously published
empirical fMRI datasets revealed robust importance maps that extensively overlap
with univariate maps but also provide complementary information. Our results
demonstrate increased statistical power of importance maps compared to univariate
approaches for both detection of overlapping patterns and patterns with weak
univariate information.
PMID- 29964191
TI - Molecular epidemiology of aminoglycoside resistance in clinical isolates of
Klebsiella pneumoniae collected from Qazvin and Tehran provinces, Iran.
AB - Production of aminoglycoside modifying enzymes (AMEs) and 16S rRNA methylases are
two main resistance mechanisms against these antibiotics. This study determined
the frequency of AMEs and 16 s rRNA methylase genes among aminoglycoside non
susceptible K. pneumoniae isolates and evaluated their clonal relationship by
enterobacterial repetitive intergenic consensus (ERIC)-PCR. A total of 177 K.
pneumoniae isolates were collected from hospitals of Qazvin and Tehran, Iran. The
identification of isolates was done by standard laboratory methods and API 20E
strips. Aminoglycosides susceptibility was determined by Kirby-Bauer method and
AMEs and 16S rRNA methylase encoding genes were studied by PCR and sequencing
methods. Clonal relatedness of isolates was assessed by ERIC-PCR method. In
total, 74% of isolates were non-susceptible to the aminoglycosides used in the
study among those kanamycin 110 (62.1%), tobramycin 91 (51.4%), and gentamycin 87
(49.2%) showed the highest rates of resistance whereas netilmicin and amikacin
revealed high susceptibility rates of 67.8% and 61.0%, respectively. Of 130
aminoglycoside non-susceptible isolates, 91.5% were positive for the presence of
aac(6')-Ib as the most dominant gene followed by aac(3)-II (78.5%), aph(3')-IIIa
(14.6%), ant(4')-Ia (3.1%), and armA (7.7%) either alone or in combination. ERIC
PCR results showed 67.7% of non-susceptible isolates had different banding
patterns followed by three distinct clones including A (16.2%), B (10.8%), and C
(5.4%). Among those isolates carrying AMEs genes, 85 (68%) isolates belonged to
independent groups and 21 (16.8%), 12 (9.6%), and 7 (5.6%) isolates belonged to
groups A, B, and C, respectively, whereas 7 (70%) of 16S rRNA methylase-producing
isolates belonged to independent groups. Our results revealed high prevalence of
AMEs with the emergence of armA genes among the genetically unrelated resistant
isolates of K. pneumonia in Iran, suggesting the need for more effective
therapeutic strategies to reduce the selection pressure and better management of
the patients infected with these resistant isolates.
PMID- 29964192
TI - Prognostic Significance of Stringent Complete Response after Stem Cell
Transplantation in Immunoglobulin Light Chain Amyloidosis.
AB - Hematologic response has emerged as a powerful prognostic factor for survival in
patients with immunoglobulin light chain (AL) amyloidosis. Patients achieving a
complete response (CR), based on serum and urine analysis, survive longest.
However, data regarding the impact of bone marrow features post-therapy on
response and survival are limited. We evaluated the impact of achieving a
stringent CR (sCR), defined as undetectable bone marrow clonal plasma cells by
flow cytometry, in patients with AL amyloidosis receiving an autologous stem cell
transplant. A total of 573 consecutive patients transplanted for AL amyloidosis
at the Mayo Clinic between April 2002 and August 2016 were included in the
analysis. Of 540 patients in whom response was assessable, 220 patients (41%)
achieved a CR, of whom 212 (96%) had a bone marrow biopsy at time of response
assessment and were further analyzed for determination of sCR; 166 patients (78%)
with a CR achieved an sCR, representing 31% of the whole cohort. Patients
achieving a CR had a higher median percentage of bone marrow plasma cells (10%
for CR versus 6% for sCR, P = .03), more patients with bone marrow plasma cells
>= 10% (50% for CR versus 33% for sCR, P = .04), and were less likely to receive
chemotherapy before transplantation (30% for CR versus 49% for sCR, P = .03)
compared with those achieving sCR. Median overall survival for all patients
achieving a CR was 175 months and was not statistically different between those
achieving an sCR compared with those achieving a CR only (median not reached for
sCR versus 175 months for CR, P = .65). Progression-free survival, however, was
significantly shorter in patients failing to achieve an sCR (151 months for sCR
versus 72 months for CR, P = .0003). Bone marrow examination post-transplant in
AL amyloidosis is important and identifies patients who fail to achieve an sCR
and progress earlier.
PMID- 29964193
TI - Impact of Lung Function on Bronchiolitis Obliterans Syndrome and Outcome after
Allogeneic Hematopoietic Cell Transplantation with Reduced-Intensity
Conditioning.
AB - Lung function deterioration contributes to treatment-related morbidity and
mortality in patients after allogeneic hematopoietic cell transplantation (allo
HCT). Better understanding of impaired lung function including bronchiolitis
obliterans syndrome (BOS) as chronic manifestation of graft-versus-host disease
(GVHD) might improve outcomes of patients after allo-HCT. To detect early
pulmonary function test abnormalities associated with BOS incidence and outcome
after allo-HCT, we performed a retrospective analysis of homogenous-treated 445
patients (median age, 61.9 years; range, 19 to 76 years) with a reduced
intensity/toxicity conditioning protocol. The cumulative incidence of BOS was
4.1% (95% confidence interval [CI], 2.6 to 6.4) at 1 year and 8.6% (95% CI, 6.3
to 11.6) at 5 years after allo-HCT with a median follow-up of 43.2 months (range,
3.3 to 209 months). In multivariate analysis, pre-existence of moderate small
airway disease reflected by decreased midexpiratory flows before allo-HCT was
associated with increased risk for BOS development. In addition, severe small
airway disease before allo-HCT and combined restrictive/obstructive lung disease
at day +100 after allo-HCT were associated with higher risk for nonrelapse
mortality (NRM) due mainly to pulmonary cause of death. In summary, we identified
novel pulmonary function test abnormalities prior and after allo-HCT associated
with BOS development and NRM. These findings might help to identify a risk
population and result in personalized GVHD prophylaxis and preventive or early
therapeutic interventions.
PMID- 29964195
TI - Identification of the thioredoxin-related protein of 14 kDa (TRP14) from
Litopenaeus vannamei and its role in immunity.
AB - The thioredoxin system plays essential roles in maintenance and regulation of the
redox state of cysteine residues in cellular proteins. The thioredoxin-related
protein of 14 kDa (TRP14) is an important member of the TRX superfamily which
acts on various substrate proteins, some of which are not overlapped with those
of thioredoxin. The knowledge on the function of TRP14 in invertebrates is
limited to date. In this study, a TRP14 gene was identified from Pacific white
shrimp Litopenaeus vannamei (LvTRP14) and its role in immune responses was
investigated. We demonstrated that the expression level of LvTRP14 was high in
hepatopancreas and intestine, low in eyestalk, and medium in other tissues of
healthy shrimp. The transcription of LvTRP14 in vivo was significantly down
regulated in Relish-silencing shrimp but up-regulated in STAT-silencing shrimp,
indicating a complex regulation of LvTRP14 expression. Although the LvTRP14
expression showed little change after immune stimulation with different type of
pathogens, knockdown of LvTRP14 expression using RNAi strategy could
significantly facilitate the infection of white spot syndrome virus (WSSV) and
Vibrio parahaemolyticus in shrimp. Dual luciferase reporter assays demonstrated
that LvTRP14 enhanced the transcription factor activity of Relish but attenuated
that of Dorsal. Furthermore, silencing of LvTRP14 in vivo had opposite effects on
expression of different type of antimicrobial peptides. These suggested that
LvTRP14 could play a complex role in shrimp immunity.
PMID- 29964194
TI - Determinants of Left Ventricular Hypertrophy and Diastolic Dysfunction in an HIV
Clinical Cohort.
AB - OBJECTIVE: The aim of this work was to investigate determinants of structural
myocardial abnormalities in persons living with human immunodeficiency virus
(PLWH). METHODS AND RESULTS: We reviewed archived transthoracic echocardiograms
(TTEs) performed on PLWH at Duke University Medical Center from 2001 to 2012. The
primary outcomes were presence of left ventricular hypertrophy (LVH) or diastolic
dysfunction (DD). TTEs for 498 human immunodeficiency virus-infected persons were
reviewed (median age 44 years, 38% female, 72% black, 34% with hypertension, 15%
with diabetes). Among those with usable images, LVH was detected in 174 of 473
persons (37%) according to LV mass criteria and in 99 of 322 persons (31%)
according to American Society of Echocardiography LV mass index criteria.
Definite DD was detected in 18 of 224 persons (8%). LVH was more common in PLWH
with a CD4 count <= 200 cells/mm3 proximal to TTE (adjusted OR 1.68, 95% CI 1.08
2.62), CD4 nadir <= 200 cells/mm3 (adjusted OR 1.63, 95% CI 1.04-2.54) and less
common in persons with viral suppression (OR 0.46, 95% CI 0.27-0.80). Lower CD4
nadirs (P = .002) and proximal CD4 counts (P = .002) were also associated with
DD. CONCLUSIONS: Persons with a history of advanced human immunodeficiency virus
associated immune suppression are at higher risk of LVH and DD than infected
persons with preserved immune function.
PMID- 29964196
TI - Identification and characterization of peroxiredoxin 1 from Lateolabrax japonicus
under biotic and abiotic stresses.
AB - The peroxiredoxins (Prxs) belong to a novel and evolutionarily conserved
superfamily, which can protect cells from oxidative damage caused by ROS and play
a vital role in immune responses. In the present study, a 995 base pairs (bp)
Prx1 cDNA sequence (LjPrx1) with an open reading frame of 594 bp, which encoding
197 amino acid polypeptides was obtained from L. japonicus. Transcriptional
expression analysis indicated that the LjPrx1 mRNA was ubiquitously expressed in
all tissues tested, while a comparatively high expression level was detected in
head-kidney and blood. After the recombinant LjPrx1 protein was acquired using a
prokaryotic expression method, the antioxidant activity was assessed by the
catalyzing hydrogen peroxide assay method, and the results showed that the
recombinant LjPrx1 possessed an antioxidant activity in a temperature-dependent
manner. To further study the function roles of LjPrx1 related to biotic and
abiotic stresses, the head-kidney and blood were chosen for the following
experiments, and a positive correlation between the expression of LjPrx1 and the
different stresses was detected using qRT-PCR. In conclusion, this study provides
useful information about the role of the LjPrx1 gene in defense against a variety
of toxic factors in L. japonicus, which would broaden our current knowledge of
Prx1.
PMID- 29964197
TI - Outcome of co-infection with opportunistic and multidrug resistant Aeromonas
hydrophila and A. veronii in zebrafish: Identification, characterization,
pathogenicity and immune responses.
AB - Fish can be potentially co-infected by two or more bacterial strains, which can
make synergistic influence on the virulence of infection. In this study, two
opportunistic and multidrug resistant Aeromonas strains were isolated from wounds
of morbid zebrafish with typical deep skin lesions similar to Motile Aeromonas
Septicemia. Isolates were genetically identified as A. hydrophila and A. veronii
by 16 S rRNA sequencing and phylogenetic analysis. Both isolates were positive
for virulent genes (aerA, lip, ser, exu gcaT) and selected phenotypic tests
(DNase, protease, gelatinase, lipase, biofilm production and beta-haemolysis). A.
hydrophila and A. veronii had strong antibiotic resistance against ampicillin,
tetracycline, nalidixic acid, kanamycin, erythromycin, clindamycin and
trimethoprim-sulfamethoxazole. Histopathological studies revealed that co
infection causes severe necrosis and hypertrophy in the muscles, kidney and liver
of zebrafish. Naturally co-infected zebrafish showed highly induced tnf-alpha, il
1beta, il-6, il-12, ifn, ifn-gamma, cxcl18 b and ccl34a.4 at transcription level
compared to healthy fish, suggesting virulence factors may activate immune and
inflammatory responses of zebrafish. Experimentally infected zebrafish showed
significantly higher mortality under co-infection with A. hydrohila and A.
veronii (87%), followed by individual challenge of A. hydrophila (72%) or A.
veronii (67%) suggesting that virulence of A. hydrophila have greater
pathogenicity than A. veronii during co-infection.
PMID- 29964198
TI - Long-term crowding stress causes compromised nonspecific immunity and increases
apoptosis of spleen in grass carp (Ctenopharyngodon idella).
AB - Crowding stress is one of the most common environmental stressors in intensive
aquaculture. To investigate the influences of long-term crowding stress on
nonspecific immune responses and apoptosis in fish, grass carp (Ctenopharyngodon
idella) were cultured at low (0.9 kg m-2), medium (2.97 kg m-2) and high (5.9 kg
m-2) stocking densities for 10 weeks in the present study. The results showed
that elevation of stocking densities caused splenic tissue damages and
inflammatory responses, which are characterized with the formation of melano
macrophage centers and the increase of granulocytes as well as significant
upregulation of inflammatory cytokine genes (il1beta and tnfalpha). The
remarkable decline in the activities of serum lysozyme, acid phosphatase and
alkaline phosphatase under high stocking density further confirmed that increased
stocking density affected fish nonspecific immune response negatively. Moreover,
the transcriptional levels of splenic apoptotic-related genes caspase-8, fasl and
caspase-3 increased significantly while the mRNA levels of bax, bcl2, apaf1 and
caspase-9 remained unchanged. This result showed that increased stocking density
caused splenic cell apoptosis, which were closely associated with the FasL
signaling pathway. Our findings revealed that crowding stress could influence
fish nonspecific immune response negatively and increase inappropriate apoptosis
of the spleen, which would make fish more susceptible to pathogens and ultimately
impair fish survival. The breeding density utilized in this study also provides
some reference values in intensive aquaculture systems from the perspective of
fish health and welfare.
PMID- 29964199
TI - Fat grafting of hairy areas of head and neck - comparison between lipofilling and
nanofat grafting procedures in a cadaveric study.
AB - AIM: Fat grafting has well-recognized effects in terms of volume gain, skin
trophicity, relieving of post-wound nevralgia. Recent publications suggest a
regenerative action on hair follicles. The objective of our study was to compare
lipofilling and nanofat grafting in hairy areas of head and neck so as to
determine a convenient fat injection technique for those areas in the prospect of
treating alopecia. MATERIAL AND METHODS: Our study compared lipofilling and
nanofat grafting, in a cadaveric study involving one body. RESULTS: Lipofilling
was found easy to perform in the face, avoiding classical pitfalls, but was more
difficult in the scalp areas. Nanofat grafting seemed particularly convenient to
inject into the scalp, especially in Merkel's space, and hairy areas that
required high precision injections. CONCLUSION: After having compared lipofilling
and nanofat grafting in hairy areas of the head and neck, we propose a
combination of lipofilling (in hairy areas where a durable gain of volume is
acceptable, in case of burn or scar) and nanofat grafting (in all hairy areas and
in Merkel's space in scalp areas). This technique may be used either as a
complement of hair follicle grafting or as a regenerative treatment of alopecia.
PMID- 29964200
TI - The cancer matrisome: From comprehensive characterization to biomarker discovery.
AB - Tumor progression and dissemination critically depend on support from the tumor
microenvironment, the ensemble of cellular and acellular components surrounding
and interacting with tumor cells. The extracellular matrix (ECM), the complex
scaffolding of hundreds of proteins organizing cells in tissues, is a major
component of the tumor microenvironment. It orchestrates cellular processes
including proliferation, migration, and invasion, that are highly dysregulated
during cancer progression. Alterations in ECM abundance, integrity, and
mechanical properties have been correlated with poorer prognosis for cancer
patients. Yet the ECM proteome, or "matrisome," of tumors remained until recently
largely unexplored. This review will present the recent developments in
computational and proteomic technologies that have allowed the comprehensive
characterization of the ECM of different tumor types and microenvironmental
niches. These approaches have resulted in the definition of protein signatures
distinguishing tumors from normal tissues, tumors of different stages, primary
from secondary tumors, and tumors from other diseased states such as fibrosis.
Moreover, recent studies have demonstrated that the levels of expression of
certain genes encoding ECM and ECM-associated proteins is prognostic of cancer
patient survival and can thus serve as biomarkers. Last, proteomic studies have
permitted the identification of novel ECM proteins playing functional roles in
cancer progression. Such proteins have the potential to be exploited as
therapeutic targets.
PMID- 29964201
TI - Clinical Nurses' Resilience Skills for Surviving in a Hospital Setting: A Q
methodology Study.
AB - PURPOSE: Resilience relates to coping with stressful hospital environment. The
purpose of this study was to identify the types of resilience skills of clinical
nurses for surviving in a hospital setting. METHODS: The Q methodology was used
as it helps analyze the participants' subjective perspective on each item.
Participants were 32 registered nurses who sorted 38 selected Q statements that
were then plotted on a normal distribution using a 9-point scale. The subjective
perspectives on the resilience of clinical nurses were analyzed using the PC
QUANAL program. RESULTS: This study revealed four types of resilience in clinical
nurses, accounting for 65.2% of the variance: Type I: Reality-harmonic type; Type
II: Own will type; Type III: Professionalism-oriented type; and Type IV: Relation
oriented type. CONCLUSION: The present findings suggest the need to develop
interventions for improving clinical nurses' resilience according to their types.
Following further investigation of nurses' resilience, it may be necessary for
organizations to develop several resilience strategies.
PMID- 29964202
TI - Unique role of epicardial adipose tissue in atrial fibrosis: "Atrial remodeling
of a new sort".
PMID- 29964203
TI - The 12-lead ECG during ventricular tachycardia: Still an important tool for
ventricular tachycardia localization in structural heart disease.
PMID- 29964204
TI - Integrin alpha5 down-regulation by miR-205 suppresses triple negative breast
cancer stemness and metastasis by inhibiting the Src/Vav2/Rac1 pathway.
AB - Triple negative breast cancer (TNBC) usually displays more aggressive metastasis,
the underlying mechanism is unclear. Previous studies showed that microRNA-205
(miR-205) has controversial roles in cancer, however, its role in TNBC metastasis
and the underlying mechanism have not been well-understood. In this study we
found that miR-205 expression level is extremely low in basal mesenchymal-like
highly migratory and invasive TNBC cells. Stably re-expressing miR-205 in TNBC
cells significantly reduced their migration, invasion capability and cancer stem
cell (CSC)-like property. Nude mouse orthotopic mammary xenograft tumor model
study revealed that miR-205 re-expression greatly decreases TNBC tumor growth and
abolishes spontaneous lung metastasis. Mechanistic studies demonstrated that miR
205 inhibits TNBC cell metastatic traits and tumor metastasis by down-regulating
integrin alpha5 (ITGA5). Moreover, ITGA5 knockout using the CRISPR/Cas9 technique
achieved the same strong inhibitory effect on TNBC cell CSC-like property and
tumor metastasis as re-expressing miR-205 did. Further mechanistic studies
indicated that ITGA5 down-regulation by miR-205 re-expression impairs TNBC cell
metastatic traits by inhibiting the Src/Vav2/Rac1 pathway. Together, our findings
suggest that miR-205 and ITGA5 may serve as potential targets for developing
effective therapies for metastatic TNBC.
PMID- 29964205
TI - Integrated transcriptomic and epigenomic analysis of ovarian cancer reveals
epigenetically silenced GULP1.
AB - Many epigenetically inactivated genes involved in ovarian cancer (OC) development
and progression remain to be identified. In this study we undertook an integrated
approach that consisted of identification of genome-wide expression patterns of
primary OC samples and normal ovarian surface epithelium along with a
pharmacologic unmasking strategy using 3 OC and 3 immortalized normal ovarian
epithelial cell lines. Our filtering scheme identified 43 OC specific methylated
genes and among the 5 top candidates (GULP1, CLIP4, BAMBI, NT5E, TGFbeta2), we
performed extended studies of GULP1. In a training set, we identified GULP1
methylation in 21/61 (34%) of cases with 100% specificity. In an independent
cohort, the observed methylation was 40% (146/365) in OC, 12.5% (2/16) in
borderline tumors, 11% (2/18) in cystadenoma and 0% (0/13) in normal ovarian
epithelium samples. GULP1 methylation was associated with clinicopathological
parameters such as stage III/IV (p = 0.001), poorly differentiated grade (p =
0.033), residual disease (p < 0.0003), worse overall (p = 0.02) and disease
specific survival (p = 0.01). Depletion of GULP1 in OC cells led to increased pro
survival signaling, inducing survival and colony formation, whereas
reconstitution of GULP1 negated these effects, suggesting that GULP1 is required
for maintaining cellular growth control.
PMID- 29964206
TI - IncU plasmid harbouring blaCTX-M-8 in multidrug-resistant Shigella sonnei in
Brazil.
PMID- 29964207
TI - Glycation induced conformational transitions in cystatin proceed to form biotoxic
aggregates: A multidimensional analysis.
AB - Hyperglycaemic conditions facilitate the glycation of serum proteins which may
have predisposition to aggregation and thus lead to complications. The current
study investigates the glycation induced structural and functional modifications
of chickpea cystatin (CPC) as well as biological toxicity of the modified protein
forms, using CPC-glucose as a model system. Several structural intermediates were
formed during the incubation of CPC with glucose (day 4, 8, 12, & 16) as revealed
by circular dichroism (CD), altered intrinsic fluorescence, and high ANS binding.
Further incubation of CPC with glucose (day 21) formed abundant beta structures
as revealed by Fourier transform infrared spectroscopy and CD analysis which may
be due to the aggregation of protein. High thioflavin T fluorescence intensity
and increased Congo red absorbance together with enhanced turbidity and Rayleigh
scattering by this modified form confirmed the aggregation. Electron microscopy
finally provided the valid physical authentication about the presence of
aggregate structures. Functional inactivation of glucose incubated CPC was also
observed with time. Single cell electrophoresis of lymphocytes and plasmid
nicking assays in the presence of modified CPC showed the DNA damage which
confirmed its biological toxicity. Hence, our study suggests that glycation of
CPC not only leads to structural and functional alterations in proteins but also
to biotoxic AGEs and aggregates.
PMID- 29964208
TI - Quantifying and Reducing Retained Botulinum Toxin Postinjection.
AB - BACKGROUND: Retained botulinum toxin solution may be visible in vials and syringe
tips after mixing and presumed complete injections, leaving patients without the
full prescribed dose. OBJECTIVE: To quantify the mean amount of retained toxin
within vials, syringes, and needles following spasticity injections (phase 1) and
to design/test a targeted intervention for reduced retained toxin (phase 2).
DESIGN: Prospective cohort quality assurance study. SETTING: Outpatient
spasticity program in a rehabilitation facility. PARTICIPANTS: Nine physicians
specializing in physical medicine and rehabilitation, performing successive
mixing and injections for spasticity with onabotulinumtoxinA or
incobotulinumtoxinA. METHODS: After initial review (phase 1), recommendations
were made (phase 2) including not inverting the vial to withdraw medication
unless needed, favoring 2-mL dilutions when possible, and decapping of vials for
more complete medication withdrawal. MAIN OUTCOME MEASUREMENTS: Retained volume
of toxin solution that was not injected and estimated retained units of toxin.
RESULTS: A total of 157 vials of botulinum toxin A were tested. Of the 82
initial, phase 1, preintervention vials (8200 units), 5.5% (~452 units) of toxin
solution was retained following mixing and injections. One and 3-mL syringe tips
contained a mean of 3.32 and 1.44 units of toxin respectively. Within vials,
saline dilutions with 2 mL contained less mean retained toxin (1.89 vs 3.31
units) relative to 1-mL dilution. Awareness of monitoring significantly decreased
retained solution in vials (0.035 mL vs 0.069 mL for naive group, P = .002).
Phase 2, postintervention testing of 75 vials demonstrated that withdrawing toxin
from the inferior edge from a non-inverted vial reduced the retained toxin by
32.8% (P < .001). Decapping the vial further reduced the mean retained toxin to
0.42 units per vial (81.9% reduction, P < .001). CONCLUSIONS: A potentially
clinically significant amount of botulinum toxin solution is retained following
mixing and injections. Implementation of guidelines significantly decreased
wasted botulinum toxin. LEVEL OF EVIDENCE: Level III.
PMID- 29964209
TI - Predictors of Performance on the American Board of Physical Medicine and
Rehabilitation Maintenance of Certification Examination.
AB - BACKGROUND: Maintenance of certification (MOC) in Physical Medicine and
Rehabilitation is a process of lifelong learning that begins after successfully
completing an Accreditation Council of Graduate Medical Education (ACGME)
accredited residency and passing the American Board of Physical Medicine and
Rehabilitation (ABPMR) Part I and Part II Examinations. We seek to identify
factors predictive of successful MOC Examination performance. OBJECTIVE: To
identify characteristics predictive of successful completion on the ABPMR MOC
Examination DESIGN: Retrospective review SETTING: American Board of Physical
Medicine and Rehabilitation database review PARTICIPANTS: 4,545 diplomates who
completed the MOC Examination between January 2006 and December 2017 METHODS: MOC
Examination performance was the primary outcome variable. Performance on Part I
and Part II Examinations were independent variables. Additional potential
predictors evaluated included year of MOC cycle in which examination was taken,
years of practice since residency completion, age, and subspecialty
certification. MAIN OUTCOME MEASURES: Performance on MOC Examination RESULTS: Age
at time of MOC Examination was inversely correlated with examination score (r =
0.14, P < .001). Similarly, as time since completion of residency training
increased, MOC scores declined. Passing the Part I Examination on first attempt
predicted a 98% MOC pass rate, compared to 90% for those who failed initially.
MOC performance was highly correlated with Part I performance (r = 0.59, P <
.001) and Part II performance (r = 0.32, P < .001). Although MOC performance was
similar for those taking the examination in years 7 - 10 of their cycle (97% pass
rate), those taking the examination after more than 10 years of the cycle had a
significantly lower performance (85% pass rate, P < .01). CONCLUSIONS: Better
performance on the MOC Examination is associated with better performance on Part
I and Part II Examinations, taking the examination earlier in the 10 year cycle,
younger age, and less time since completion of training. Diplomates who are at
higher risk for failing the examination may need to prepare differently for MOC
Exam than those who are more likely to pass. LEVEL OF EVIDENCE: III.
PMID- 29964210
TI - Can a Brief Training Session Prepare Physician Sonographers of Differing
Experience to Measure the Ischiofemoral Space? A Reliability Study.
AB - OBJECTIVE: The primary aim of this study was to determine the inter- and
intrarater reliability of ultrasound (US) measurements of the ischiofemoral space
(IFS) following a brief training session. A secondary aim was to determine if
reliability correlated with sonographer experience. DESIGN: Prospective. SETTING:
Physical medicine and rehabilitation department within a tertiary care
institution. PARTICIPANTS: Seven male and 3 female individuals were recruited to
serve as models. Nine physician sonographers (3 postgraduate year [PGY]-2
residents, 3 PGY-4 residents, 3 physicians) were recruited to serve as
sonographers. METHODS OR INTERVENTIONS: Sonographers received a 15-minute
educational session on identifying the IFS with US, followed by 20 minutes of
practice. Models were then placed in a prone position and secured to prevent hip
movement. All operators measured bilateral IFSs in each model twice with a
washout period between measurements. Operators were blinded to all measurements.
MAIN OUTCOME MEASURES: Primary outcomes were inter- and intrarater reliability
interclass coefficients (ICCs) of IFS measurements among the groups with
different levels of US experience. Secondary outcomes included comparisons of
inter- and intrarater reliability ICCs of IFS measurements between groups, and
the difference of mean IFS measurements between groups. RESULTS: Intrarater
reliability ICCs were 0.829, 0.680, and 0.596 for physician, PGY-4, and PGY-2
groups, respectively. Interrater reliability ICCs were 0.722, 0.427, and 0.558
for physician, PGY-4, and PGY-2 groups, respectively. No statistically
significant differences in reliability were identified between groups. Mean IFS
measurements were 31.2, 33.4, and 34.0 mm for physician, PGY-4, and PGY-2 groups,
respectively. Physician measurements were significantly smaller than the PGY-4
and PGY-2 measurements (P < .049 and P < .01). CONCLUSIONS: Following a brief
training session, experienced sonographers demonstrated excellent IFS measurement
intrarater reliability, whereas PGY-4 and PGY-2 sonographers demonstrated fair
intrarater reliability. All sonographers demonstrated fair interrater
reliability. LEVEL OF EVIDENCE: II.
PMID- 29964211
TI - Botulinum Toxin: Techniques Within Pediatric Physiatry.
AB - BACKGROUND: Intramuscular botulinum toxin injections are used for treatment of
focal spasticity in children, particularly in those with a diagnosis of cerebral
palsy. There are a variety of techniques used when performing botulinum toxin
injections without clear standards for pediatric providers. OBJECTIVE: To
describe current practice techniques for botulinum toxin injections among
pediatric physiatrists. DESIGN: Cross-sectional survey using RedCap Software.
SETTING: Pediatric physiatrists who perform botulinum toxin injections.
PARTICIPANTS: Survey of 307 pediatric physiatrists. METHODS: Analysis of data
from the 2017 practice survey of pediatric physiatrists in the United States.
MAIN OUTCOME MEASUREMENTS: Physicians were asked the primary botulinum toxin
used, common dosing information, the role of localization, and the role of
sedation and distraction in their practice. RESULTS: Nearly all pediatric
physiatrists use OnabotulinumtoxinA as the primary formulation of botulinum
toxin. The maximum dose per body weight used per injection series had a median of
15 units/kilogram and a median maximum total dose of 500 units. Sixty-five
percent of pediatric physiatrists report using sedation, of any type, for
botulinum toxin injections. When using sedation, the most common primary method
was general anesthesia (38.9%), followed by enteral or nasal anxiolytic with the
patient awake (26.2%). The most common reported intended injection site for
botulinum toxin was "in multiple sites spread throughout the muscle" (67.9%), and
then "one site of the muscle at the motor point" (17.1%). Large muscles were
injected using primarily anatomic guidance (75.6%) and electromyography (50.8%),
and small muscles were primarily completed with electromyography (73.6%) and
anatomic guidance (49.2%). CONCLUSION: There is considerable variability present
in one common procedure performed by pediatric physiatrists. LEVEL OF EVIDENCE:
Level IV.
PMID- 29964212
TI - Dextromethorphan/Quinidine for Pseudobulbar Affect Following Stroke: Safety and
Effectiveness in the PRISM II Trial.
AB - BACKGROUND: Dextromethorphan (DM) / quinidine (Q) was approved for pseudobulbar
affect (PBA) treatment based on efficacy and safety trials in patients with PBA
caused by amyotrophic lateral sclerosis or multiple sclerosis. The PRISM II trial
evaluated DM/Q as PBA treatment in patients with stroke, dementia, or traumatic
brain injury. OBJECTIVE: To report results from the stroke cohort of PRISM II,
including the Stroke Impact Scale (SIS). DESIGN: Open-label trial evaluating
twice-daily DM/Q over 90 days. STUDY PARTICIPANTS: Adults (n = 113) with a
clinical diagnosis of PBA secondary to stroke; stable psychiatric medications
were allowed. METHODS: PRISM II was an open-label, 12-week trial enrolling adults
with PBA caused by dementia, stroke (reported here), or TBI. All study
participants received DM/Q 20/10 mg twice daily. Study visits occurred at
baseline and at days 30 and 90. SETTING: 150 U.S. centers. MAIN OUTCOME
MEASUREMENTS: Primary efficacy measure was changed from baseline to day 90 in
Center for Neurologic Study-Lability Scale (CNS-LS) scores. Secondary outcomes
included PBA episodes (estimated over 7 days), Clinical and Patient/Caregiver
Global Impression of Change (CGI-C and PGI-C), Quality of Life-Visual Analog
Scale (QOL-VAS), SIS, Patient Health Questionnaire (PHQ-9), and Mini-Mental State
Examination (MMSE). RESULTS: Compared with baseline, CNS-LS scores (SD) improved
by -6.2 (6.1, P < .001) at day 30 and -7.6 (6.7, P < .001) at day 90. PBA
episodes were reduced by 65% and 75% at day 30 and 90, respectively. Seventy-five
percent of clinicians and 67% of patients/caregivers rated PBA as "much" or "very
much improved." All SIS items significantly improved from baseline (P < .05,
all). Adverse events included diarrhea (4.4%), headache (3.5%), constipation
(2.7%), and dizziness (2.7%); 5.3% had adverse events leading to study
discontinuation. CONCLUSIONS: DM/Q effectively treated PBA and was associated
with global and functional improvement; adverse events were consistent with the
known safety profile of DM/Q.
PMID- 29964213
TI - Cardiovascular Risk Factors Among Older Adults With Long-Term Spinal Cord Injury.
AB - BACKGROUND: Individuals with spinal cord injury (SCI) now live longer, which
increases the risk of cardiovascular disease. Knowledge of cardiovascular risk
factors amenable to intervention are therefore needed to support their healthy
aging. OBJECTIVE: To describe the occurrence of cardiovascular risk factors among
older adults with long-term SCI and investigate the association with
sociodemographics and injury characteristics. DESIGN: Cross-sectional descriptive
cohort study. SETTING: Home settings. PARTICIPANTS: In total, 123 individuals
(71% men, injury levels C1-L5, American Spinal Injury Association Impairment
Scale A-D), mean age 63 years, mean time since injury 24 years. METHODS: Data
from the Swedish Aging with Spinal Cord Injury Study (SASCIS), collected through
interviews and assessments during home visits and from medical records. MAIN
OUTCOME MEASURES: Anthropometric measurements, blood pressure, fasting plasma
glucose and blood lipids, and data on cardiovascular comorbidity and tobacco use.
RESULTS: One third had a previous diagnosis of hypertension, and 55% presented
with a blood pressure >=140/90 mm Hg at the time of assessment. Sixteen percent
had a history of diabetes and in 15% fasting glucose levels were >=7 mmol/L.
Dyslipidemia was present in 76%, whereas 16% had prediagnosed dyslipidemia. Mean
body mass index (BMI) was 27 kg/m2 and mean waist circumference was 101 cm. When
SCI-adjusted BMI cut-off values were used, 93% were considered overweight (BMI
>=22 kg/m2), and 60% had a waist circumference associated with cardiometabolic
risk. A total of 16% smoked regularly. The median number of cardiovascular risk
factors was 3. No significant associations were found between the total number of
risk factors and sociodemographics and injury characteristics. CONCLUSIONS: The
high occurrence of cardiovascular risk factors among older adults with long-term
SCI can pose additional consequences to their health. Regular assessments and
interventions targeting cardiovascular risk in this population are therefore
warranted. Further research is needed to identify modifiable factors associated
with their risk profile. LEVEL OF EVIDENCE: III.
PMID- 29964214
TI - Safety Considerations in Prescription of NSAIDs for Musculoskeletal Pain: A
Narrative Review.
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the
treatment of painful musculoskeletal conditions. When prescribing oral NSAIDs,
clinicians must consider coexisting cardiovascular, cerebrovascular,
gastrointestinal, and renal disease because oral NSAIDs are associated with a
broad spectrum of adverse effects on these systems. The different safety profiles
of NSAIDs can be attributed to differences in the extent to which the drug
inhibits cyclo-oxygenase-1 vs -2 and their potential for drug-drug interactions.
This narrative review intends to guide the clinician in prescribing oral NSAIDs
while taking into consideration these comorbid conditions and drug interactions.
PMID- 29964215
TI - Pregnancy Results in Lasting Changes in Knee Joint Laxity.
AB - BACKGROUND: Altered joint laxity can contribute to joint dysfunction. Knee joint
laxity has been shown to increase during pregnancy, but its long-term persistence
is unknown. OBJECTIVE: To determine whether pregnancy leads to lasting increases
in knee joint compliance and laxity that persist longer than 4 months postpartum.
DESIGN: Prospective cohort study. SETTING: A motion analysis laboratory at an
academic medical center. PARTICIPANTS: Fifty healthy women in their first
trimester of pregnancy (mean +/- SD 29.2 +/- 4.3 years old and baseline body mass
index 26.0 +/- 5.4 kg/m2) were recruited. INTERVENTION: End-range knee laxity and
midrange joint compliance were measured during the first trimester and 19 +/- 4
weeks postpartum. Anterior-posterior and varus-valgus laxity were measured using
3-dimensional motion tracking while applying forces and moments in each
respective plane using the Vermont Knee Laxity Device. Nonlinear models were
constructed to assess relations between applied forces and joint translation,
comparing early pregnancy with postpartum. OUTCOMES: Multiplanar knee laxity and
compliance. RESULTS: Peak varus-valgus (20-22%; P = .001) and posterior
translation (51%; P < .001) of the tibia relative to the femur decreased from
baseline, with a concomitant decrease in laxity (P < .001) and compliance (P =
.039) in the coronal plane and in the posterior direction in primiparous (P =
.009) and multiparous (P = .014) women. For primiparous women, laxity (P < .001)
and compliance (P = .009) increased in the anterior direction. CONCLUSIONS:
Pregnancy resulted in a lasting decrease in multiplanar knee laxity and
compliance in the varus and posterior directions with an increase in anterior
compliance. The effects of these changes in laxity and compliance of the passive
stabilizers on knee loading patterns, articular contact stresses, and risk for
osteoarthritis and other musculoskeletal disorders will require additional
research.
PMID- 29964216
TI - Nociceptive and Cognitive Changes in a Murine Model of Polytrauma.
AB - Polytrauma commonly involves concussion (mild traumatic brain injury [mTBI]) and
peripheral trauma including limb fractures. Interactions between mTBI and
peripheral injuries are poorly understood, both leading to chronic pain and
neurobehavioral impairments. To elucidate these interactions, a murine polytrauma
model was developed. mTBI alone resulted in similar increased mechanical
allodynia in male and female mice. Female fracture and polytrauma groups
displayed greater increases in hind paw tactile hypersensitivity for weeks after
injury than did the respective male groups. Capsaicin-evoked spontaneous pain
behaviors were greater in fracture and polytrauma female mice compared with male
mice. The mTBI and polytrauma male mice displayed significant deficits in spatial
working memory. All fracture, mTBI, or polytrauma groups had deficits in object
recognition memory. Only male mTBI or polytrauma mice showed greater agitation
and increased risk-taking behavior in open field testing as well as zero maze
tests. Additionally, impaired diffuse noxious inhibitory control was observed in
all mTBI and polytrauma mice. The model presented offers clinically relevant
features useful for studying persistent pain as well as cognitive and other
behavioral changes after TBI including polytrauma. A better understanding of
nervous system dysfunction after TBI and polytrauma might help prevent or reduce
persistent pain and disability in these patients. PERSPECTIVE: The polytrauma
model presented has relevant features of chronic pain and neurobehavioral
impairments useful for studying mechanisms involved in their development. This
model may have special value in understanding altered descending pain modulation
after TBI and polytrauma.
PMID- 29964217
TI - IMTB 2017 Conference: At the intersection of microfluidics and biotechnology.
PMID- 29964218
TI - In vitro and in vivo investigation of PLA/PCL scaffold coated with metformin
loaded gelatin nanocarriers in regeneration of critical-sized bone defects.
AB - Large bone defects constitute a major challenge in bone tissue engineering and
usually fail to heal due to the incomplete differentiation of recruited
mesenchymal stem cells (MSCs) into osteogenic precursor cells. As previously
proposed, metformin (MET) induces differentiation of MSCs into osteoblastic
lineages in vitro. We fabricated a Poly (lactic acid) and Polycaprolactone
(PLA/PCL) scaffold to deliver metformin loaded gelatin nanocarriers (MET/GNs) to
critical-sized calvarial bone defects in a rat model. The scaffolds were
evaluated regarding their morphology, porosity, contact angle, degradation rate,
blood compatibility, biomechanical, cell viability and their osteogenic
differentiation. In animal study, the defects were filled with autograft,
scaffolds and a group was left empty. qRT-PCR analyses showed the expression
level of osteogenic and angiogenic markers considerably increased in MET/GNs
PLA/PCL. The in vivo results showed that MET/GNs-PLA/PCL improved bone ingrowth,
angiogenesis and defect reconstruction. Our results represent the applicability
of MET/GNs-PLA/PCL for successful bone regeneration.
PMID- 29964219
TI - Core-shell nanoparticles for targeted and combination antiretroviral activity in
gut-homing T cells.
AB - A major sanctuary site for HIV infection is the gut-associated lymphoid tissue
(GALT). The alpha4beta7 integrin gut homing receptor is a promising therapeutic
target for the virus reservoir because it leads to migration of infected cells to
the GALT and facilitates HIV infection. Here, we developed a core-shell
nanoparticle incorporating the alpha4beta7 monoclonal antibody (mAb) as a dual
functional ligand for selectively targeting a protease inhibitor (PI) to gut
homing T cells in the GALT while simultaneously blocking HIV infection. Our
nanoparticles significantly reduced cytotoxicity of the PI and enhanced its in
vitro antiviral activity in combination with alpha4beta7 mAb. We demonstrate
targeting function of our nanocarriers in a human T cell line and primary cells
isolated from macaque ileum, and observed higher in vivo biodistribution to the
murine small intestines where they accumulate in alpha4beta7+ cells. Our LCNP
shows the potential to co-deliver ARVs and mAbs for eradicating HIV reservoirs.
PMID- 29964220
TI - Aortic plaque-targeted andrographolide delivery with oxidation-sensitive micelle
effectively treats atherosclerosis via simultaneous ROS capture and anti
inflammation.
AB - Inflammation and oxidative stress are two major factors that are involved in the
pathogenesis of atherosclerosis. A smart drug delivery system that responds to
the oxidative microenvironment of atherosclerotic plaques was constructed in the
present study. Andrographolide-loaded micelle was assembled from the block
copolymer of poly(ethylene glycol) and poly(propylene sulphide) (PEG-PPS) for the
purpose of simultaneously decreasing inflammatory response and the level of
reactive oxygen species (ROS) to treat atherosclerosis. Owing to the ROS
responsive nature of PEG-PPS, the micelle not only serves as a stimuli-responsive
drug carrier to quickly release the encapsulated drug, andrographolide, but also
consumes ROS by itself at the pathologic sites, upon which the expressions of pro
inflammatory cytokines are effectively suppressed and oxidative stress is
alleviated. Consequently, the andrographolide-loaded micelle demonstrated
remarkable therapeutic effects both in vitro and in vivo. In conclusion, the
andrographolide-loaded PEG-PPS micelle can synchronically alleviate inflammation
and oxidative stress, providing a promising and innovative strategy against
atherosclerosis.
PMID- 29964221
TI - Multifunctional nanoparticles for trimodal photodynamic therapy-mediated
photothermal and chemotherapeutic effects.
AB - Herein, we posit a biocompatible and pH-switchable integrated nano-delivery of
CBP/ICG to the in vitro and in vivo experiments demonstrate that nanoparticles
(NPs) have insignificant toxicity and good biocompatibility, and possess
excellent tumor targeting efficiency as evidenced by highly efficient tumor
ablation under near -infrared (NIR) illumination. In addition, we have conjugated
folic acid as a targeting ligand for folate receptor-targeted delivery.
Particularly, targeted delivery of dual CBP/ICG loaded NPs provide targeted
detection and transporting potential to specific receptor-expressing tumors, and
then CBP interfering with DNA damage and ICG generates singlet oxygen as well as
photothermal heat when irradiated with NIR for simultaneous trimodal
PDT/PTT/Chemotherapy. Using an animal model, a dramatic reduction in tumor growth
without any evidence of significant long-term toxicity to organs after
administration of NPs for trimodal therapy subjecting to NIR illumination. Thus,
the in vivo satisfactory antitumor trimodal combined efficacy concurrent with
complete tumor eradication and promising potential for advanced clinical
phototherapy.
PMID- 29964222
TI - Violet LED with low concentration carbamide peroxide for dental bleaching: A case
report.
AB - The use of violet LED was recently introduced as a new alternative technique to
perform tooth bleaching, associated or not with bleaching agents. This paper
shows a tooth bleaching clinical case report performed in a 26-year-old woman,
using a violet LED with 10% carbamide peroxide (CP). The tooth bleaching protocol
was performed in 3 sessions. Fifteen irradiations using a violet light system
(BMW, MMoptics, Sao Carlos, SP, Brazil) were done during 30 s (on) and 60 s (off)
without bleaching gel, and more 5 irradiations associated to 10% CP. Upper and
lower arches were irradiated separately. The total procedure time was 30 min.
Subjective and objective color assessments were performed using Vitapan Classical
shade guide and VITA Easyshade spectrophotometer, respectively. Dentin
sensitivity was measured using a visual analogue scale. The use of violet LED
associated to a low concentration carbamide peroxide successfully promoted tooth
bleaching and no side effects i.e. dentin sensitivity during and post treatment
was observed.
PMID- 29964223
TI - Silica nanoparticles embedded with water insoluble phthalocyanines for the
photoinactivation of microorganisms.
AB - Silica nanoparticles (SiNPs) embedded with Zn(II) 2,9,16,23
tetrakis(methoxy)phthalocyanine (SiNPZnPcOCH3), Zn(II) 2,9,16,23-tetrakis(4
pyridyloxy) phthalocyanine (SiNPZnPcOPy) and Zn(II) 2,9,16,23-tetrakis(t-butyl)
phthalocyanine (SiNPZnPctBu) were synthesized in the nonpolar core of AOT/1
butanol/water micelles using triethoxyvinylsilane and 3
aminopropyltriethoxysilane. These SiNPs-Pc presented an average diameter of about
20-25 nm. UV-vis absorption spectra presented the characteristic Soret and Q
bands of phthalocyanines embedded into the nanoparticles. Moreover, red
fluorescence emission of SiNPs bearing phthalocyanines was detected in water. The
SiNPs-Pc produced the photodecomposition of 2,2'-(anthracene-9,10
diyl)bis(methylmalonic acid), which was used to sense the singlet molecular
oxygen O2(1Deltag) generation in aqueous medium. Also, the formation of
superoxide anion radical was detected by nitro blue tetrazolium reduction in the
presence of NADH. Photoinactivation of microorganisms was investigated in
Staphylococcus aureus and Candida albicans. In vitro experiments showed that
photosensitized inactivation induced by SiNPZnPcOCH3 and SiNPZnPctBu improved
with an increase of irradiation times. After 30 min irradiation, over 7 log
reduction was found for S. aureus. Also, these SiNPs-Pc produced a decrease of
2.5 log in C. albicans after 60 min irradiation. In both cases, a lower
photoinactivation activity was found for SiNPZnPcOPy. Studies of photodynamic
action mechanism showed that the photokilling of microbial cells was protected in
the presence of sodium azide and diazabicyclo[2.2.2]octane. Also, a reduction on
the cell photodamage was found with the addition of D-mannitol. Therefore, the
photodynamic activity sensitized by SiNPZnPcOCH3 and SiNPZnPctBu in microbial
cells was mediated by a contribution of both type I and type II photooxidative
mechanisms. Thus, silica nanoparticles are interesting materials to vehicle
ZnPcOCH3 and ZnPctBu in aqueous media to photoeradicate microorganisms.
PMID- 29964224
TI - ALA-PDT suppressed the cell growth by Akt-/Erk-mTOR-p70 s6k pathway in human SZ95
sebocytes in vitro.
AB - BACKGROUND: Topical 5-aminolevulinic acid mediated photodynamic therapy (PDT) is
known to be an effective method in treating acne vulgaris and other sebaceous
gland-related diseases. The therapeutic mechanisms of ALA-PDT still remain
undetermined. Our team has reported that ALA-PDT suppressed the cell growth in
SZ95 sebocytes by mTOR-p70 S6K signaling. In this study, we aimed to investigate
upstream of the mammalian target of rapamycin (mTOR) signaling cascade after ALA
PDT on cell growth of human SZ95 sebocytes. MATERIAL AND METHODS: Human SZ95
sebocytes were treated with different concentration of 5-ALA PDT. Western
blotting was used to detect and analyze the protein expression level of P-Akt
(T308)/Akt, P-Akt (S473)/Akt, P-Erk/Erk, P-AMPKalpha (T172)/AMPK, P-AMPKalpha1
(S485)/AMPKalpha2 (S491)/AMPK, P-PRAS40/PRAS40, RagC. Meanwhile, mTOR pathway
activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the
interferences of P-p70 S6K/p70 S6K after ALA-PDT. RESULTS: mTOR pathway inhibitor
rapamycin decreased the level of P-p70 S6K reduced by ALA-PDT. Conversely, mTOR
pathway activator IGF-1. ALA-PDT reduced the level of P-Akt (T308), P-Erk, P
AMPKalpha (T172), P-AMPKalpha1 (S485)/AMPKalpha2 (S491) and P-PRAS40, and no
change was observed in the level of Rag C. CONCLUSION: ALA-PDT suppresses the
cell growth in SZ95 cells through Akt-/Erk- mTOR -p70 s6k pathway rather than
PRAS40-/RagC- mTOR pathway.
PMID- 29964225
TI - Mary Hewitt Loveless, MD: The origin of venom immunotherapy.
PMID- 29964226
TI - A combination visual analog scale as an integrated outcome for assessing the
perception of allergen immunotherapy effectiveness in clinical practice.
PMID- 29964227
TI - Efficacy of C1 inhibitor concentrate in hereditary angioedema with C1 inhibitor
deficiency: Analysis in a French cohort.
PMID- 29964228
TI - Health literacy and asthma among Hispanic and African-American urban adolescents
with undiagnosed asthma.
PMID- 29964229
TI - Are third-generation cephalosporins associated with a better prognosis than
amoxicillin-clavulanate in patients hospitalized in the medical ward for
community-onset pneumonia?
AB - OBJECTIVES: We aimed to assess whether treatment with ceftriaxone/cefotaxime is
associated with lower in-hospital mortality than amoxicillin-clavulanate in
pati0ents hospitalized in medical wards for community-onset pneumonia. METHODS:
We conducted a retrospective and multicentre study of patients hospitalized in
French medical wards for community-onset pneumonia between 2002 and 2015.
Treatments with ceftriaxone/cefotaxime or amoxicillin-clavulanate were defined by
their start in the emergency department for a duration of 5 days or more with no
other beta-lactam. A logistic regression analysis was performed on the overall
population, and a propensity score analysis was restricted to patients treated
with either ceftriaxone/cefotaxime or amoxicillin-clavulanate. RESULTS: 1698
patients (median age, 80 y) were included, of which 716 and 198 were treated with
amoxicillin-clavulanate and ceftriaxone/cefotaxime, respectively. In-hospital
mortality was 10% (9-12%). In multivariate analysis, factors associated with in
hospital mortality were treatment with ceftriaxone/cefotaxime (aOR 2.9; (1.4
5.7)), pneumonia severity index class 4 or 5 (aOR 7.8 (4.3-15.7)), do-not
resuscitate order (aOR 8.7 (5.2-14.6)) and fluid therapy (aOR 6.3 (2.5-15.1)).
The propensity score analysis was performed on 178 patients treated with
ceftriaxone/cefotaxime matched with 178 patients treated with amoxicillin
clavulanate; no significant association between treatment with
ceftriaxone/cefotaxime and in-hospital mortality was found (OR 1.5 (0.7-3.0)).
CONCLUSION: In the largest study aiming to compare amoxicillin-clavulanate and
ceftriaxone/cefotaxime in community-onset pneumonia, ceftriaxone/cefotaxime was
not associated with lower in-hospital mortality than amoxicillin-clavulanate. Our
results suggest that ceftriaxone/cefotaxime should not be preferred over
amoxicillin-clavulanate for patients hospitalized in medical wards with community
onset pneumonia.
PMID- 29964230
TI - Risk factors for recurrence in patients with Clostridium difficile infection due
to 027 and non-027 ribotypes.
AB - OBJECTIVES: Our objective was to evaluate factors associated with recurrence in
patients with 027+ and 027- Clostridium difficile infection (CDI). METHODS:
Patients with CDI observed between January and December 2014 in six hospitals
were consecutively included in the study. The 027 ribotype was deduced by the
presence of tcdB, tcdB, cdt genes and the deletion Delta117 in tcdC (Xpert(r) C.
difficile/Epi). Recurrence was defined as a positive laboratory test result for
C. difficile more than 14 days but within 8 weeks after the initial diagnosis
date with reappearance of symptoms. To identify factors associated with
recurrence in 027+ and 027- CDI, a multivariate analysis was performed in each
patient group. Subdistributional hazard ratios (sHRs) and 95% confidence
intervals (95%CIs) were calculated. RESULTS: Overall, 238 patients with 027+ CDI
and 267 with 027- CDI were analysed. On multivariate analysis metronidazole
monotherapy (sHR 2.380, 95%CI 1.549-3.60, p <0.001) and immunosuppressive
treatment (sHR 3.116, 95%CI 1.906-5.090, p <0.001) were factors associated with
recurrence in patients with 027+ CDI. In this patient group, metronidazole
monotherapy was independently associated with recurrence in both mild/moderate
(sHR 1.894, 95%CI 1.051-3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281
4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437-9.524, p
0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155-125.000, p
0.007) were associated with recurrence in 027- CDI. CONCLUSIONS: Compared to
vancomycin, metronidazole monotherapy appears less effective in curing CDI
without relapse in the 027+ patient group, independently of disease severity.
PMID- 29964231
TI - Update on vaccines for enteric pathogens.
AB - BACKGROUND: Acute diarrhoeal disease caused by viral, bacterial and parasitic
infections is a major global health problem; in low- and middle-income countries
(LMICs) it is associated with substantial mortality and morbidity in children
under 5. Some of these infections also impact large segments of populations in
high-income countries (HICs), as well as individuals who travel overseas for
work, business or pleasure. AIMS: The aim of this review is to describe the
current landscape of licensed enteric vaccines, potential new vaccines on the
horizon, and the challenges of development and utilization of vaccines against
enteric pathogens. SOURCES: Relevant data from the literature, as well as
clinical trials described in European and US registries, were examined in the
conduct of this review. CONTENT: The review involves discussion of current
licensed vaccines against rotavirus, cholera and typhoid, as well as potential
second- and third-generation vaccines against these pathogens currently in the
development pipeline. In addition, novel vaccines against enterotoxigenic
Escherichia coli, shigellosis and norovirus in advanced development are
described. Challenges to the development and utilization of global vaccines are
discussed. IMPLICATIONS: Despite advances in population health, food security,
improved sanitation and water quality, and the reduction in poverty, acute
enteric infections continue to plague global populations. Advancing utilization
of current enteric vaccines is of critical public health importance, as is the
development of new vaccines, particularly for enteric pathogens where none
currently exist.
PMID- 29964232
TI - Pentraxin 3 in bronchoalveolar lavage fluid and plasma in non-neutropenic
patients with pulmonary aspergillosis.
AB - OBJECTIVES: Pentraxin 3 (PTX3) contributes to resistance to Aspergillus
infections. This study aimed to evaluate the presence of PTX3 in bronchoalveolar
lavage fluid (BALF) and plasma in non-neutropenic patients with pulmonary
aspergillosis. METHODS: BALF (n = 211) and plasma samples (n = 307) were
collected from patients initially suspected of having pulmonary aspergillosis.
Among these, 112 cases (51 BALF samples and 89 plasma samples) were proven to be
pulmonary aspergillosis. These cases were classified as invasive pulmonary
aspergillosis (IPA), subacute invasive aspergillosis (SAIA) and chronic pulmonary
aspergillosis (CPA). The remaining cases were non-aspergillosis controls and were
diagnosed with community-acquired pneumonia (CAP), lung cancer and pulmonary
cryptococcosis. Plasma samples from healthy controls (n = 30) were also
collected. RESULTS: The median (interquartile range, IQR) BALF PTX3 for
aspergillosis cases was significantly higher than for non-aspergillosis cases:
6.97 (2.91-13.51) ng/mL versus 1.26 (0.76-1.76) ng/mL. When the PTX3 threshold
was set at 1.9 ng/mL, sensitivity and specificity of BALF PTX3 for aspergillosis
were 86.3% (95%CI 83.8-88.4%) and 82.5% (95%CI 79.7-85.0%), respectively. The
median (IQR) plasma PTX3 for aspergillosis cases was significantly higher than
for non-aspergillosis cases and healthy controls: 7.10 (3.36-9.53) ng/mL versus
1.57 (0.86-2.35) ng/mL versus 1.10 (0.49-1.51) ng/mL. With a PTX3 threshold of
2.3 ng/mL, sensitivity and specificity were 79.8% (95%CI 70.1-81.2%) and 72.1%
(95%CI 69.5-74.5%) respectively. CONCLUSIONS: BALF and plasma PTX3 may be
biomarkers for differentiating aspergillosis from other conditions such as CAP,
lung cancer, and pulmonary cryptococcosis in non-neutropenic patients.
PMID- 29964233
TI - Estimation of missed bloodstream infections without the third blood culture set:
a retrospective observational single-centre study.
AB - OBJECTIVES: The question of whether to obtain two or three sets of blood cultures
to assess the aetiology of bloodstream infections (BSIs) remains open to debate.
Few studies have assessed the proportion of BSIs missed without the third blood
culture set (BCS). The aim of our study was to determine the proportion of BSIs
that would be missed without the third BCS in a hospital where obtaining three
BCSs is the standard of care. METHODS: We performed a descriptive retrospective
study in Hospital Gregorio Maranon (Madrid) from 2010 to 2013. We included all
episodes of BSI in which three BCSs were systematically obtained. RESULTS: We
included 4000 episodes of BSI between 2010 and 2013. Without the third BCS, we
would have missed 298 (7.5%) episodes of BSI: 141 (47.3%) by gram-positive
microorganisms, 147 (49.3%) by gram-negative microorganisms, and 10 (3.4%) by
yeasts. In 132/298 (44.3%) of the episodes another clinical sample was obtained
within a week of the BCS extraction; in 101/298 (33.9%), the same microorganism
was present in a significant clinical sample other than blood. CONCLUSIONS: Our
data suggest that performing a third BCS is useful, as not doing this could
result in an unacceptable number of BSIs going undetected.
PMID- 29964234
TI - CMI website collections.
PMID- 29964235
TI - Relationship between enteric pathogens and acute gastroenteritis disease
severity: a prospective cohort study.
AB - OBJECTIVES: To evaluate the relationship between individual bacterial and viral
pathogens and disease severity. METHODS: Children <18 years with three or more
episodes of vomiting and/or diarrhoea were enrolled in two Canadian paediatric
emergency departments between December 2014 and August 2016. Specimens were
analysed employing molecular panels, and outcome data were collected 14 days
after enrolment. The primary outcome was severe disease over the entire illness
(symptom onset until 14-day follow-up), quantified employing the Modified
Vesikari Scale (MVS) score. The score was additionally analysed in two other time
periods: index (symptom onset until enrolment) and follow-up (enrolment until 14
day follow-up). RESULTS: Median participant age was 20.7 (IQR: 11.3, 44.2)
months; 47.4% (518/1093) and 73.4% (802/1093) of participants had index and total
MVS scores >=11, respectively. The most commonly identified pathogens were
rotavirus (289/1093; 26.4%) and norovirus (258/1093; 23.6%). In multivariable
analysis, severe disease over the entire illness was associated with rotavirus
(OR = 9.60; 95%CI: 5.69, 16.19), Salmonella (OR = 6.61; 95%CI: 1.50, 29.17),
adenovirus (OR = 2.53; 95%CI: 1.62, 3.97), and norovirus (OR = 1.43; 95%CI: 1.01,
2.01). Pathogens associated with severe disease at the index visit were:
rotavirus only (OR = 6.13; 95%CI: 4.29, 8.75), Salmonella (OR = 4.59; 95%CI:
1.71, 12.29), adenovirus only (OR = 2.06; 95%CI: 1.41, 3.00), rotavirus plus
adenovirus (OR = 3.15; 95%CI: 1.35, 7.37), and norovirus (OR = 0.68; 95%CI: 0.49,
0.94). During the follow-up period, rotavirus (OR = 2.21; 95%CI: 1.50, 3.25) and
adenovirus (OR = 2.10; 95%CI: 1.39, 3.18) were associated with severe disease.
CONCLUSIONS: In children presenting for emergency department care with acute
gastroenteritis, pathogens identified were predominantly viruses, and several of
which were associated with severe disease. Salmonella was the sole bacterium
independently associated with severe disease.
PMID- 29964237
TI - Empathy.
PMID- 29964236
TI - Association of Decreased C1q/Tumor Necrosis Factor-Related Protein-5 Levels with
Metabolic and Hormonal Disturbance in Polycystic Ovary Syndrome.
AB - OBJECTIVE: C1q/tumor necrosis factor-related protein-5 (CTRP5) is a novel
secreted peptide hormone involved in metabolism of energy regulation. Polycystic
ovary syndrome (PCOS) which is a reproductive and metabolic disorder is
associated with insulin resistance. The target of the current study was
comparison of circulating levels of CTRP5 in women with and without PCOS and
investigation of possible associations between CTRP5 and metabolic-hormonal
parameters. MATERIAL AND METHODS: The present cross-sectional study contained a
group of 80 women with PCOS and a group of 80 women without PCOS with having age-
and body mass index-matched. Circulating levels of CTRP5 were calculated
considering enzyme-linked immunosorbent assay. We also measured hormonal and
metabolic parameters. RESULTS: PCOS subjects represented lower levels of
circulating CTRP5 when compared with the women without PCOS (6.90 +/- 2.64 vs.
11.73 +/- 3.66 ng/ml, P < 0.001). CTRP5 was negatively correlated with insulin
resistance, free-androgen index (FAI), and body mass index in both PCOS and
control groups. Moreover, PCOS patients having insulin resistance showed lower
circulating CTRP5 levels compared to those without insulin resistance. In both
the control and PCOS groups, overweight subjects had lower circulating levels of
CTRP5 compared to participants with normal weight. Logistic regression analyses
indicated that subjects in the lowest tertile for CTRP5 level had higher risk of
PCOS compared to those subjects in the highest tertile of CTRP5. CONCLUSION:
Decreased circulating levels of CTRP5 were associated with higher risk of PCOS,
as well as having metabolic disturbance among women with PCOS.
PMID- 29964238
TI - Sources of oral pain.
PMID- 29964239
TI - Erratum.
PMID- 29964240
TI - The impact of bioactive materials on cosmetic restorative dentistry.
PMID- 29964241
TI - The prescription opioid abuse crisis and our role in it.
PMID- 29964242
TI - High-fidelity simulation training for management of dental emergencies.
PMID- 29964243
TI - What every dentist and patient should know about accelerated orthodontic tooth
movement.
AB - Within the last few decades, an increasing number of adults have sought
orthodontic therapy. One disadvantage of pursuing orthodontic treatment in
adulthood is the lengthened time span required to complete tooth movement. The
purpose of this article is to review the biologic mechanisms of accelerated tooth
movement as well as the literature on nonsurgical and surgical techniques that
may reduce the duration of orthodontic treatment.
PMID- 29964244
TI - Utilization of cone beam computed tomography to determine the prevalence and
anatomical characteristics of bifurcated inferior alveolar nerves.
AB - The primary purpose of this study was to evaluate the prevalence of inferior
alveolar nerve (IAN) bifurcations through the utilization of cone beam computed
tomography (CBCT). The secondary purposes of this study were to analyze the
average distance from the main trunk to its branch at the greatest point, to
calculate the average distance of the bifid IAN from the apices of the teeth, and
to determine the appropriate classification for each IAN bifid nerve according to
the types described by Nortje et al: type 1, 2 canals originating from a single
foramen with a narrower inferior canal; type 2, 2 canals originating from a
single foramen with a superior canal extending to the second or third molar; type
3, 2 canals of equal size that arise from 2 mental foramina that may link into a
single canal near the molars. Examination of 194 CBCT scans revealed that IAN
bifurcations were present in 13.4% (n = 26) of the study population. Bifurcation
was bilateral in 4 individuals. For left bifurcated IANs, the average distance
between the superior border of the main branch and inferior border of the
bifurcated IAN (GDN) was 3.41 mm. The average distance from the superior border
of the bifurcated IAN to the apex of the closest root (NAP) was 3.45 mm. For
right bifurcated IANs, the average GDN was 4.01 mm, and the average NAP was 4.85
mm. Fourteen bifid nerves were type 1, and 16 were type 2. Preoperative CBCT
studies can determine the presence of a bifurcated IAN, thereby reducing the
chances of neurologic damage.
PMID- 29964245
TI - Fracture resistance of bonded CAD/CAM restorations with standard or extended
preparations.
AB - The purpose of this study was to evaluate the fracture resistance of teeth with
standard or extended mesio-occlusodistal (MOD) preparations after restoration
with bonded computer-aided design/computer-aided manufacturing (CAD/CAM)
materials. Standard or extended MOD cavities were prepared in 60 of 70 extracted,
caries-free third molars. In the standard MOD preparations (n = 30), 4.5- mm
buccal and lingual/palatal wall thickness remained, and proximal boxes extended
1.0 mm coronal to the cementoenamel junction. In the extended MOD preparations (n
= 30), the buccal and lingual/palatal walls were reduced to a thickness of 3.0
mm. A CAD/CAM acquisition unit was used to scan 20 standard and 20 extended
preparations. Subsequently, 10 standard and 10 extended preparations were
restored with milled lithium disilicate, and 10 of each type were restored with
resin nanoceramic. Ten of each preparation type were left unrestored (negative
control). An additional 10 third molars were neither prepared nor restored
(positive control). After thermocycling and cyclic loading, specimens were
fractured in a material testing device. Although bonded CAD/CAM restorations
reinforced the tooth structure, the mean fracture loads were significantly lower
(P < 0.05) in teeth with restored extended preparations (2642.4 [SD 479.4] N)
than in teeth with restored standard preparations (3376.6 [SD 817.9] N). The type
of CAD/CAM restorative material did not significantly affect the fracture load.
Practitioners should consider covering the cusps with a CAD/CAM restorative
material to reduce the potential for fracture in preparations with reduced cuspal
thickness, especially in patients with heavier occlusion or functional loads.
PMID- 29964246
TI - Diagnostic accuracy of panoramic radiography and MRI for detecting signs of TMJ
degenerative joint disease.
AB - The objective of this study was to determine the diagnostic accuracy of panoramic
radiography and magnetic resonance imaging (MRI) for detection of signs of
temporomandibular joint (TMJ) degenerative joint disease (DJD). Panoramic
radiography and bilateral MRI and computed tomography (CT) of the TMJs were
performed for 705 subjects. Three calibrated board-certified radiologists who
were blinded to the clinical findings interpreted all images. The diagnoses of
DJD established using the panoramic radiographs and MRIs were compared to the
reference standard diagnoses derived from the CTs. DJD was defined as the
presence of at least 1 of the following 4 signs: a subcortical cyst, surface
erosion, osteophyte formation, or generalized sclerosis. The target values for
sensitivity and specificity were 70% or greater and 95% or greater, respectively.
Compared to the reference standard CTs, the panoramic radiographs had the
following sensitivity and specificity values: subcortical cysts, 14% and 100%,
respectively; erosion, 20% and 100%, respectively; osteophytes, 12% and 100%,
respectively; and sclerosis, 33% and 100%, respectively. The MRIs achieved the
following sensitivity and specificity values: subcortical cysts, 32% and 100%
respectively; erosion, 35% and 99% respectively; osteophytes, 71% and 98%,
respectively; and sclerosis, 50% and 100%, respectively. The radiologists'
interexaminer reliability was slight (kappa = 0.16) when using panoramic
radiographs, moderate (kappa = 0.47) when using MRIs, and substantial when using
CTs (kappa = 0.71) for diagnosis of signs of DJD. Panoramic radiographs and MRIs
had below-target sensitivity but above-target specificity in detecting all CT
depicted signs of DJD with the exception of osteophytes, for which MRIs
demonstrated adequate diagnostic accuracy. Use of CT for diagnosis of TMJ DJD is
recommended to avoid the false-negative findings that can occur if panoramic
radiographs and MRIs are used.
PMID- 29964247
TI - Retentive force variations of stud attachments for implant overdentures.
AB - Implant overdentures are considered a standard treatment option by many
practitioners, especially for edentulous mandibles. Stud attachments have been
used extensively in the construction of these overdentures. In this study, the
retentive forces of O-ring/ball and Locator overdenture attachments under various
conditions in the mouth were investigated through pull-out tests. In dry testing,
the retentive forces of the O-ring/ball attachment started higher than those of
the Locator attachment but significantly decreased after 50 insertion-removal
cycles (P = 0.014). The Locator attachment had no significant change in its
retentive force over time (P = 0.328). In wet testing, a saliva substitute was
applied to the stud attachments between cycles. The retentive force of the O
ring/ball attachment increased significantly in wet testing compared to dry
testing (P < 0.0001). The retentive force of the Locator system during wet
testing did not change significantly from that achieved during dry testing for
the first 80 cycles, but then it increased to reach the same levels as the O
ring/ball system at 510 cycles (P < 0.05). Within the limitations of the present
study, the results suggest that it is advisable to avoid using O-ring/ball
attachments as anchors for implant overdentures in a dry mouth environment. In
such cases, Locator attachment or metal-to-metal attachment components would be
preferable as implant overdenture anchors. In a saliva-irrigated mouth, there is
no significant difference between the retentive properties of the O-ring/ball and
Locator attachments over 6-9 months' use.
PMID- 29964248
TI - Multidisciplinary management of an impacted maxillary central incisor associated
with supernumerary teeth: a case report.
AB - Permanent maxillary central incisor impaction is a rare condition of
multifactorial etiology that should be treated on diagnosis. This article
describes multidisciplinary treatment of an 11-year-old patient presenting with a
permanent maxillary right central incisor that was impacted due to the presence
of 2 supernumerary teeth. The diagnosis was reached through clinical evaluation,
radiography, and cone beam computed tomography. Treatment involved the surgical
removal of the supernumerary teeth followed by traction of the impacted tooth
through a combination of removable and fixed orthodontic appliances. Orthodontic
treatment was completed after 18 months, resulting in adequate positioning of the
right central incisor in the arch. Periodic follow-up visits were scheduled for
prophylaxis and oral hygiene reinforcement. After 2 years, the teeth were
adequately aligned, the gingiva was healthy, and the patient was esthetically
satisfied. The multidisciplinary approach allowed functional and esthetic oral
rehabilitation, thus helping the patient to avoid the psychological impact of a
missing anterior tooth.
PMID- 29964249
TI - Evaluation of marginal leakage after mechanical fatigue cycling of composite
inlays luted with different cements.
AB - This in vitro study evaluated the marginal microleakage of composite inlays luted
with 3 different cement systems. The null hypothesis was that the luting
materials would not influence dye penetration, showing the same degree of
microleakage. Thirty-six sound molars were selected, mesio-occlusodistal cavities
were prepared, and the teeth were randomly divided into 3 groups (n = 12).
Composite resin inlay restorations were made and cemented using a dual-curing
resin cement (Calibra), a light-curing flowable composite (Charisma Flow), or a
self-adhesive resin cement (RelyX Unicem). The restored teeth were subjected to
fatigue cycles and immersed in 0.5% basic fuchsin dye for 24 hours. Two
orthogonal cuts were made to enable evaluation of dye penetration at the cervical
and occlusal margins. The sections were evaluated with a 4-point scale ranging
from 0 (no penetration) to 3 (penetration up to the cavity floor [occlusal
margins] or axial wall [cervical margins]). The Calibra and Charisma Flow groups
showed greater microleakage, notably at the cervical margins, whereas RelyX
Unicem specimens showed the least dye penetration. Significant differences were
found between the Calibra and Charisma Flow groups and between the Charisma Flow
and RelyX Unicem groups (P < 0.05). No statistically significant differences were
detected between the Calibra and RelyX Unicem groups. The microleakage associated
with the flowable composite was significantly greater than that associated with
both resin cements, results that discourage its use for luting of Class II
composite inlays.
PMID- 29964250
TI - Autoimmune temporomandibular arthropathy: diagnostic considerations.
AB - The etiology of degenerative processes of the temporomandibular joint (TMJ)
remains unclear, as they could be the result of trauma, infection, or autoimmune
disease. Improving the diagnosis of autoimmune disease, whether the TMJ is the
primary site or secondarily affected by a systemic disease, is of fundamental
importance in selecting treatment that will address the causes rather than just
relieve the symptoms. The purposes of this article are to discuss autoimmunity as
an etiologic factor in degenerative processes of the TMJ by presenting clinical
cases and to highlight the importance of imaging and serologic examinations for
diagnosis.
PMID- 29964251
TI - Complete overdenture fabrication for a 12-year-old child with dentinogenesis
imperfecta type 2.
AB - Dentinogenesis imperfecta type 2 (DI-2), also known as hereditary opalescent
dentin, is a rare, genetically linked condition that affects both primary and
permanent teeth. Severe attrition requiring full-mouth rehabilitation is a common
finding associated with DI-2. Dental rehabilitation options include a variety of
invasive and noninvasive restorative techniques dictated by the age of the
patient. Growth and development must be considered and may result in a
restorative challenge for the dental practitioner, particularly when the patient
in question is a child. This case report describes the fabrication of an
overdenture to reestablish function, esthetics, and self-esteem in a 12-year-old
patient. A 2-stage restorative treatment was followed by a satisfactory 6-month
recall examination, indicating that the prostheses provided a successful outcome
until more definitive restorative treatment can be accomplished in adulthood.
PMID- 29964252
TI - Effect of a dentifrice containing nanohydroxyapatite on the roughness, color,
lightness, and brightness of dental enamel subjected to a demineralization
challenge.
AB - The dental profession is still pursuing the most effective way to treat white
spot lesions in order to produce a sound and esthetically pleasing enamel
surface. The aim of the present research was to evaluate in vitro the effects of
a dentifrice with nanohydroxyapatite (nano-HAp) on the roughness, color,
lightness, and brightness (gloss) of bovine enamel subjected to pH cycling.
Twelve enamel discs prepared from bovine incisors were divided into 2
experimental groups: dentifrice with sodium fluoride (Colgate Total 12 Clean
Mint) and dentifrice with nanoHAp (Megasonex). For 14 days, the specimens were
subjected to 30 cycles of simulated brushing twice a day as well as to a pH
cycling model (6 hours of demineralization and 18 hours of remineralization
daily). The roughness, color, lightness, and brightness of all specimens were
evaluated at baseline (immediately after specimen preparation) and after 7 and 14
days of treatment. A Tukey test demonstrated that there were no statistically
significant differences in the effects of the dentifrices on any parameter after
7 days (P > 0.05). After 14 days, however, there was a statistically significant
increase in mean roughness in the group brushed with fluoride dentifrice (P <
0.05). Thus, the nanoHAp containing dentifrice promoted less superficial
roughness after 14 days, but both dentifrices were similar in relation to color
variation, lightness, and brightness.
PMID- 29964253
TI - Reimplantation of an avulsed mature permanent tooth after 6 days: a 1-year follow
up.
AB - Tooth avulsion in children and adolescents demands emergency treatment to
increase the chances of successful reimplantation. The treatment prognosis
depends on intrinsic and extrinsic factors, such as the extra-alveolar time until
reimplantation, storage medium, handling, and periodontal ligament condition of
the avulsed tooth as well as the patient's general health. This case report
describes the treatment of an 11-year-old boy who suffered an avulsion of the
maxillary right central incisor followed by delayed reimplantation after the
tooth was stored in a dry medium for 6 days. Although the tooth was kept in
extremely unfavorable conditions, tooth reimplantation was attempted because the
patient was young and it was desirable to avoid psychological trauma as well as
esthetic and functional problems. The treatment performed followed the guidelines
of the International Association of Dental Traumatology for an avulsed tooth with
a closed apex and extraoral dry time exceeding 60 minutes. At a 1-year follow-up
appointment, the tooth exhibited clinical function, no mobility or pain symptoms,
and mild signs of ankylosis. A radiographic image showed resorption by
substitution. Although the long-term prognosis is uncertain, this treatment
approach was advantageous for the patient because it maintained esthetics,
function, and alveolar bone height.
PMID- 29964254
TI - Unusual tongue. Painful tongue.
PMID- 29964255
TI - Surgical reconstruction of the interdental papilla: 2 case reports.
AB - The loss of interdental papillae may create esthetic and phonetic problems and
facilitates food impaction. Nonsurgical and surgical approaches can be developed
to restore these areas, depending on the amount of tissue lost. Periodontal
surgical techniques are difficult to perform in the interdental space because of
the limited amount of tissue and poor blood supply. The aim of this article is to
describe a periodontal plastic surgical technique in which subepithelial
connective tissue grafts associated with composite restorations are used to
reconstruct interdental papillae. This approach was followed in 2 patients whose
grafts were obtained from different donor sites: the palate and the retromolar
tuberosity. The 12-month recall examinations of both patients revealed
satisfactory results, including stable gingival margins and complete, harmonious
fill of the interdental papillary areas.
PMID- 29964256
TI - Experimental morphologic study of reparative processes in erosive lesions of the
oral mucosa.
AB - The goal of this preclinical study was to substantiate the effectiveness of using
autologous platelet-rich plasma (PRP) to heal erosive lesions in the oral cavity.
This study employed analyses of qualitative and semiquantitative morphologic
parameters, including histologic assessment of biopsy specimens. The most
favorable results were observed in a group of 16 dogs receiving 2-mL injections
of autologous PRP 3 times: day 1 of the experiment and after 7 and 14 days of
observation; in this group, no traces of inflammatory symptoms were found at the
end of the observation period (14 days). At the end of the same time period, a
control group of 16 dogs receiving conventional therapy-which consisted of twice
daily applications of an anesthetic agent, proteolytic enzymes, an antiseptic
agent, and a wound healing preparation-exhibited signs of nonspecific chronic
inflammation in certain zones of the oral mucosa. These results suggest that
autologous PRP may be useful in the treatment of various inflammatory disorders
in the maxillofacial area.
PMID- 29964257
TI - [Upcoming value of gene expression analysis in rheumatology].
AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology,
which involves disturbance in immune system signaling pathway functions, damage
of other tissues, pain and joint destruction. Modern treatment attempts to
improve pathophysiological and biochemical mechanisms damaged by the disease.
However, due to the RA patient heterogeneity personalized approach to treatment
is required; the choice of personalized treatment is complicated by the
variability of patient's response to treatment. Gene expression analysis might
serve a tool for the disease control and therapy personification for inhibition
of inflammation and pain as well as for prevention of joint destruction.
PMID- 29964258
TI - [Comparative proteomic profiling of nuclear and cytosolic fractions from cell
lines of different origin].
AB - Proteomic analysis of the nuclear fraction is of great importance, since many
cellular processes are initiated in the nucleus. Refinement and choice of
experimental procedures for cell lysate fractionation and parameters for mass
spectrometric detection and data processing continue to be of current interest.
The mass spectrometry analysis presented here was tested on human cell lines
derived from different tissues: HL-60 (peripheral blood); HepG2 (liver); EA.hy926
(vascular endothelium). High reproducibility of results and their consistency
with biological properties of the objects under study were demonstrated. The use
of cells of different types made it possible to reveal a set of 16 proteins whose
LFQ-values allow for the discrimination between proteome fractions regardless of
cell origin. Also, a set of 16 proteins is suggested which are associated with
individual characteristics of cell lines regardless of cell fraction. These
protein panels can serve as parameters to verify the proteomic analysis done was
of sufficient quality, in particular as indicators of successful fractionation of
cell or tissue lysate.
PMID- 29964259
TI - [Hepatoprotective activity of aqueous extract from Caragana jubata (Pall.) Poir.
shoots in the model of acute hepatitis induced by acetaminophen in rats].
AB - The aim of the study was to investigate the hepatoprotective activity of an
aqueous extract of Caragana jubata (Pall.) Poir. Acute experimental hepatitis was
induced by acetaminophen administration of 1000 mg/kg. Studies were conducted in
white Wistar rats. The aqueous extract of C. jubata demonstrated the
hepatoprotective effect, comparable to that of the reference preparation
"Carcil". This was manifested by the normalization of biochemical blood
parameters (ALT, AST, alkaline phosphatase, cholesterol, total bilirubin) and
antioxidant activity of liver homogenates, determined by the method based on
oxidation of luminol induced by 2,2c-azo-bis-2-amidinopropane. Normalization of
morphofunctional indices was also shown in a histological study of liver of rats
that received aqueous extract from C. jubata.
PMID- 29964260
TI - [Creation of a generalized model prediction of inhibition of neuraminidase of
influenza virus of various strains].
AB - Preliminary results of construction of overall model for prediction of IC50 value
of ligands of influenza virus neuraminidase of any strain are presented. We used
MM-PBSA (MM-GBSA) energy terms calculated for the complexes obtained after
modeling of 30 variants of neuraminidase structures, subsequent docking and
simulation of molecular dynamics as independent variables in prediction
equations. The structures of known neuraminidase-inhibiting drugs (oseltamivir,
zanamivir and peramivir) and a neuraminidase substrate (MUNANA) were used as
ligands. The correlation equation based on calculated energetic parameters of
inhibitor complexes with neuraminidase did not result in the prediction of IC50
with acceptable parameters (R2L0.3). However, if information about binding energy
of the substrate used for neuraminidase assay (and IC50 detection) is included
the resulting IC50 prediction equations become significant (R230.55). It is
concluded that models based on IC50 values as a predictable variable and
combining information about binding of different ligands to different variants of
the target proteins must take into account the binding properties of the
substrate (used for IC50 determination). The predictive power of such models
depends critically on the quality of the modeling of the ligand-protein
complexes.
PMID- 29964261
TI - [Improving of HDL capacity for macrophages cholesterol efflux after plasma
incubation with phospholipid nanoparticles].
AB - In connection with recent data about antiatherogenic importance of not only
plasma HDL concentration, but of their cell cholesterol efflux capacity as well,
the possibility of its correction by phospholipid (PL) nanoparticles was studied.
Blood plasma was incubated with earlier elaborated PL nanoparticles emulsion with
the particle diameter up to 30 nm, and HDL cholesterol efflux capacity of apo B
depleted plasma was studied. Using macrophages THP-1 preloaded 3H-cholesterol
were used. The addition of incubated plasma supernatants with the elevated PL/apo
A-1 ratio to cell media resulted in almost increase in two fold 3H-cholesterol
efflux as compared with native HDL. The maximal efflux was observed at the PL/apo
A-1 ratio of 1.06 as compared with native apo B-depleted plasma (the PL/apo A-1
ratio of 0.85). Results suggest possible usage of ultrasmall PL nanoparticles for
regeneration of impaired antiatherogenic HDL functionality. This approach seems
to be predominant compared with the usage of PL emulsions with detergent or
apoprotein A1.
PMID- 29964262
TI - [The effect of acute hypoxia with hypercapnia on the content of monoamines in
symmetrical areas of the brain in albino mice].
AB - Changes in the activity of monoaminergic systems of the left and right
hemispheres of the brain after acute hypoxia with hypercapnia were investigated
in male albino mice. The concentrations of dopamine (DA), serotonin (5-HT) and
their metabolites dihydroxyphenylacetic (DOPAC), homovanilic (HVA) and 5
hydroxyindolacetic (5-HIAA) acids were measured by HPLC in the brain cortex,
hippocampus and striatum of the right and the left hemispheres. In the control
mice not exposed to hypoxia with hypercapnia, a higher concentration of DA in the
left cortex was detected. No asymmetry in the content of other substances has
been identified in the investigated structures. Acute hypoxia with hypercapnia
led to the right-sided increase of DA and 5-HT levels and to the left-sided
reduction DOPAC in the cerebral cortex. Under the condition of hypoxia with
hypercapnia, in the hippocampus, the left-sided increase of the DA content was
revealed. In the striatum the contents of monoamines and their metabolites were
insignificantly changed. It has been concluded that acute hypoxia with
hypercapnia causes asymmetric changes in monoaminergic systems of the archicortex
and the neocortex.
PMID- 29964263
TI - [The effect of biguanide derivatives on oxidative stress in rats with
hyperglycemia].
AB - The effect of the synthetic biguanide derivatives N-[imino(1
piperidinyl)methyl]guanidine (NIPMG) and 1,3-dimethyl-5
[(carbamimidamidomethanimidoil) amino]benzoyl-1,3dicarboxylate (DCB) on the
degree of proteins oxidative modification (POM) and the DNA fragmentation, the
content of the lipid peroxidation primary products - conjugated dienes (CD), and
the activity of glutathione antioxidant system in the liver and heart of rats
with experimental hyperglycemia was investigated. Administration of the
biguanides (15.0 mg/kg) to hypoglycemic rats promoted reduction of the free
radical processes intensity in the studied tissues. Data about CD and POM level
changes in hyperglycemic rats treated by NIPMG and DKB correlate with the results
of DNA fragmentation degree evaluation. At the same time, the activity of
antioxidant enzymes (glutathione peroxidase and glutathione reductase), and the
reduced glutathione content in the liver and heart of rats changed toward control
values. For metformin, which was used as a comparison drug, changes in the
studied parameters in the same direction were also found. These results indicate
the ability of the tested biguanide derivatives to exhibit a positive regulatory
effect on free radical homeostasis, reducing the degree of oxidative stress at
this pathology.
PMID- 29964264
TI - [Lipoilcarnosine: synthesis, study of physico-chemical and antioxidant
properties, biological activity].
AB - Synthesis of lipoilcarnosine (LipC) - a conjugated molecule based on two natural
antioxidants, carnosine and a-lipoic acid, is described. Its physico-chemical,
antioxidant properties and biological activity are characterized. According to
reversed-phase HPLC with a UV detector, purity of the final product was 89.3%.
The individuality of the obtained sodium salt of LipC was confirmed by tandem
HPLC-mass spectrometry. High resistance of LipC to hydrolysis with serum
carnosinase was demonstrated. The antioxidant activity of LipC measured by
reaction with the formation of thiobarbituric acid reacting substances and
kinetic parameters of iron-induced chemiluminescence was higher than that of
carnosine and lipoic acid. LipC did not affect viability of SH-SY5Y human
neuroblastoma culture cells, differentiated towards the dopaminergic type, at
concentrations not exceeding 5 mM. At the concentration range of 0.1-0.25 mM LipC
protected neuronal cells against 1-methyl-4-phenylpyridinium (MPP + )-induced
toxicity.
PMID- 29964265
TI - [A rational approach to obtaining high-specific polyclonal antibodies against
recombinant alpha-synuclein].
AB - The approach for the quick and efficient production ofpolyclonal antibodies tothe
target antigen alpha-synuclein has been proposed. Two methods have been employed
to purify specific rabbit polyclonal antibodies against recombinant human alpha
synuclein, produced by subcutaneous immunization with complete Freund's adjuvant.
It was shown that purification on CNBr-activated Sepharose with immobilized alpha
synuclein resulted in antibody preparation with rabbit serum histidine-rich
glycoprotein as a contaminant. Two-stage antibody purification procedure first on
Sepharose with immobilized protein G, and then on alpha-synuclein immobilized
column helps to avoid contamination and to obtain homogenous antibody
preparation. Antibodies recognize different conformations of alpha-synuclein and
can be used in a variety of immunochemical approaches, including
immunocytochemistry.
PMID- 29964266
TI - [Primary screening of substances-photosensibilizers of the bacteriochlorin range
for photodynamic therapy of malignant neoplasms].
AB - This paper presents a primary screening of bacteriochlorin-type compounds with
aminoamide, propyl and carbohydrate substituents aimed for development a new
generation photosensitizers (PS) for photodynamic therapy of malignant tumors.
Absorption and fluorescence spectral characteristics of the compounds, their
storage stability in solutions under dark conditions and light exposure, photo
induced and dark cytotoxicity against human HEp2 tumor cells have been studied.
It has been shown that the dyes with aminoamide substituents have an absorbtion
maximum at 754+/-2 nm in the long wavelength region and they are not stable
during storage (the specific fluorescence intensity decreased by 33-56% during 24
hours). The long wavelength region absorption of the propyl and carbohydrate
substituted compounds varied in the range 780-831 nm, they were stable in
solutions during storage and under light irradiation. Except the dye with a
carbohydrate residue in the exocycle E, all PS exhibited the high photo-induced
activity and low level of the dark cytotoxicity. The highest photo-induced
cytotoxicity was observed for compounds with aminoamide substituents inthe
macrocyclic ring (IC 50 values ranged from 17 nM to49 nM after 2 hour incubation
with PS followed by exposure to the 10 J/cm 2 dose of red light). Taking into
account the totality of the physico-chemical and biological properties, as well
as manufacturability of production, O-propyloxime-N-propoxybacteriopurinimide
methyl ester was chosen as the most promising candidate compound for further
investigations.
PMID- 29964267
TI - [Features of redox processes in the amniotic fluid at placental insufficiency].
AB - Activity of prooxidant enzymes (NADPH-oxidase and xanthine oxidase), antioxidant
enzymes (superoxide dismutase (SOD) and catalase), enzymes of the glutathione
dependent systems, as well as antioxidant vitamins (retinol and a-tocopherol),
lipid peroxidation products (LPP) (conjugated dienes and Schiff bases), and
peroxide chemiluminescence were studied in the amniotic fluid at different
periods of physiological pregnancy and placental insufficiency (PI). It was found
that at PI the activity of NADPH-oxidase, xanthine oxidase increased and the
activity of SOD, catalase, glutathione peroxidase, glutathione reductase,
glutathione transferase and the content of fat-soluble vitamins decreased. The
direct and inverse correlation between the studied pro- and antioxidant
parameters and the content of LPP products, was found ro be different in the II
and III trimesters of gestation. The revealed differences obviously reflect
metabolic impairments in the fetoplacental complex, and the activity and level of
the paremeters of redox processes can be used as tests for pre- and postnatal
disorders.
PMID- 29964268
TI - Tailoring exchange bias in ferro/antiferromagnetic FePt3 bilayers created by He+
beams.
AB - We report on artificial exchange bias created in a continuous epitaxial FePt3
film by introducing chemical disorder using a He+ beam, which features tailorable
exchange bias strength through post-irradiation annealing. By design, the
ferromagnetic (FM)/antiferromagnetic (AF) heterostructure exhibits stratified
degrees of chemical order; however, the chemical composition and stoichiometry
are invariant throughout the film volume. This uniquely allows for a
consideration purely of the magnetic exchange across the FM/AF interface without
the added hindrance of structural boundary parameters which inherently affect
exchange bias quality. Annealing at 840 K results in the strongest exchange
biased system, which displays a cross-sectional morphology of fine (<10 nm)
domain structure composed of both of chemically ordered and chemically disordered
domains. A magnetic model developed from fitting the characteristic polarised
neutron reflectometry spectral features reveals that dual interactions can be
attributed to the observed exchange bias: magnetic coupling at the FM/AF
interface and also between neighbouring FM (chemically disordered) and AF
(chemically ordered) domains within the nominally FM layer. Our results indicate
that exchange bias is hindered at interfaces which are both chemically and
magnetically perfect, while annealing can be used to balance the volume
proportions of interfacial FM and AF domains to enhance the magnetic interface
roughness for customisable exchange bias in mono-stoichiometric FM/AF
heterostructures crafted by ion beams.
PMID- 29964269
TI - A method for predicting non-equilibrium thermal expansion using steepest-entropy
ascent quantum thermodynamics.
AB - Steepest-entropy-ascent quantum thermodynamics (SEAQT) is an intriguing approach
that describes equilibrium and dynamic processes in a self-consistent way. To
date, it has been applied primarily to gas phase systems because of the
difficulty in generating the complex eigenstructures (eigenvalues and
eigenfunctions) associated with solid or liquid phases. In this contribution, the
SEAQT modeling is extended to the solid phase by constructing a so-called pseudo
eigenstructure, and its applicability is demonstrated by calculating the thermal
expansion of metallic silver for three cases: (a) stable equilibrium, (b) along
three irreversible paths from different initial non-equilibrium states to stable
equilibrium, and (c) along an irreversible path between two stable equilibrium
states. The SEAQT framework with an anharmonic pseudo-eigenstructure predicts
reasonable values for the equilibrium thermal expansion. For the irreversible
cases considered, the SEAQT approach makes it possible to predict the time
dependence of lattice relaxations from the initial state to the final equilibrium
state.
PMID- 29964270
TI - 3D matters! 3D-RISM and 3D convolutional neural network for accurate
bioaccumulation prediction.
AB - In this work, we present a new method for predicting complex physical-chemical
properties of organic molecules. The approach utilizes 3D convolutional neural
network (ActivNet4) that uses solvent spatial distributions around solutes as
input. These spatial distributions are obtained by a molecular theory called
three-dimensional reference interaction site model. We have shown that the method
allows one to achieve a good accuracy of prediction of bioconcentration factor
which is difficult to predict by direct application of methods of molecular
theory or simulations. Our research demonstrates that combination of molecular
theories with modern machine learning approaches can be effectively used for
predicting properties that are otherwise inaccessible to purely theory-based
models.
PMID- 29964271
TI - Extinction of auditory threat memory triggers activation of p70 S6 kinase 1 in
the basolateral nucleus of the amygdala.
PMID- 29964272
TI - Things We Do For No Reason: Blood Cultures for Uncomplicated Skin and Soft Tissue
Infections in Children.
AB - Skin and soft tissue infections (SSTIs) are common pediatric diagnoses in both
outpatient and inpatient settings. Blood cultures are frequently obtained for
evaluation of SSTIs. Multiple studies have demonstrated that blood cultures
rarely demonstrate true pathogenic bacterial growth, and even positive cultures
do not change clinical management. Obtaining blood cultures has been associated
with increased length of hospital stay. In addition, false-positive blood
cultures may occur and result in repeat blood cultures and increased hospital
charges. Clinicians should avoid obtaining blood cultures in pediatric patients
with uncomplicated SSTIs but instead should focus on obtaining wound cultures
when possible.
PMID- 29964273
TI - The Inpatient Blindside: Comorbid Mental Health Conditions and Readmissions among
Hospitalized Children.
PMID- 29964274
TI - Mental Health Conditions and Unplanned Hospital Readmissions in Children.
AB - OBJECTIVE: Mental health conditions (MHCs) are prevalent among hospitalized
children and could influence the success of hospital discharge. We assessed the
relationship between MHCs and 30-day readmissions. METHODS: This retrospective,
cross-sectional study of the 2013 Nationwide Readmissions Database included
512,997 hospitalizations of patients ages 3 to 21 years for the 10 medical and 10
procedure conditions with the highest number of 30-day readmissions. MHCs were
identified by using the International Classification of Diseases, 9th Revision
Clinical Modification codes. We derived logistic regression models to measure the
associations between MHC and 30-day, all-cause, unplanned readmissions, adjusting
for demographic, clinical, and hospital characteristics. RESULTS: An MHC was
present in 17.5% of medical and 13.1% of procedure index hospitalizations.
Readmission rates were 17.0% and 6.2% for medical and procedure hospitalizations,
respectively. In the multivariable analysis, compared with hospitalizations with
no MHC, hospitalizations with MHCs had higher odds of readmission for medical
admissions (adjusted odds ratio [AOR], 1.23; 95% confidence interval [CI], 1.19
1.26] and procedure admissions (AOR, 1.24; 95% CI, 1.15-1.33). Three types of
MHCs were associated with higher odds of readmission for both medical and
procedure hospitalizations: depression (medical AOR, 1.57; 95% CI, 1.49-1.66;
procedure AOR, 1.39; 95% CI, 1.17-1.65), substance abuse (medical AOR, 1.24; 95%
CI, 1.18-1.30; procedure AOR, 1.26; 95% CI, 1.11-1.43), and multiple MHCs
(medical AOR, 1.43; 95% CI, 1.37-1.50; procedure AOR, 1.26; 95% CI, 1.11-1.44).
CONCLUSIONS: MHCs are associated with a higher likelihood of hospital readmission
in children admitted for medical conditions and procedures. Understanding the
influence of MHCs on readmissions could guide strategic planning to reduce
unplanned readmissions for children with cooccurring physical and mental health
conditions.
PMID- 29964275
TI - ERRATUM TO: Cardiac Troponins in Low-Risk Pulmonary Embolism Patients: A
Systematic Review and Meta-Analysis.
AB - The authors would like to make the following corrections to their manuscript,
Cardiac Troponins in Low-Risk Pulmonary Embolism Patients: A Systematic Review
and Meta-Analysis (doi: 10.12788/jhm.2961), published online first April 25, 2018
(all corrections in bold): The last sentence of the results section in the
abstract should read: The pooled likelihood ratios (LRs) for all-cause mortality
were positive LR 2.04 [95% CI, 1.53 to 2.72] and negative LR 0.72 [95% CI, 0.37
to 1.40]. In the "All studies pooled" of the last row of Table 2, Tn+ is
corrected to 463. On page E5, the first paragraph in the "Outcomes of Studies
with Corresponding Troponin+ and Troponin-" section beginning with the fifth
sentence should read as follows): "In the pooled data, 463 (67%) patients tested
negative for troponin and 228 (33%) tested positive. The overall mortality (from
sensitivity analysis) including in-hospital, 30-day, and 90-day mortalities was
1.2%. The NPVs for all individual studies and the overall NPV are 1 or
approximately 1. The overall PPVs and by study were low, ranging from 0 to 0.60.
The PLRs and NLRs were not estimated for an outcome within an individual study if
none of the patients experienced the outcome. When outcomes were only observed
among troponin-negative patients, such as in the study of Moore (2009) who used
30-day all-cause mortality, the PLR had a value of zero. When outcomes were only
observed among troponin-positive patients, as for 30-day all-cause mortality in
the Hakemi9(2015), Lauque10 (2014), and Lankeit16 (2011) studies, the NLR had a
value of zero. For zero cells, a continuity correction of 0.5 was applied. The
pooled likelihood ratios (LRs) for all-cause mortality were positive LR 2.04 [95%
CI, 1.53 to 2.72] and negative LR 0.72 [95% CI, 0.37 to 1.40]. The OR for all
cause mortality was 4.79 [95% CI 1.11 to 20.68, P = .0357].
PMID- 29964276
TI - The Association of Inpatient Occupancy with Hospital-Acquired Clostridium
difficile Infection.
AB - Few studies have evaluated the relationship between high hospital occupancy and
hospital-acquired complications. We evaluated the association between inpatient
occupancy and hospital-acquired Clostridium difficile infection (CDI) using a
novel measure of hospital occupancy. We analyzed administrative data from
California hospitals from 2008-2012 for Medicare recipients aged 65 years with a
discharge diagnosis of acute myocardial infarction, heart failure, or pneumonia.
Using daily census data, we constructed patient-level measures of occupancy on
admission day and average occupancy during hospitalization (range: 0-1), which
were split into 4 groups. We used logistic regression with cluster standard
errors to estimate the adjusted and unadjusted relationship of occupancy with
hospital-acquired CDI. Across 327 hospitals, 558,344 discharges met our inclusion
criteria. Higher admission day occupancy was associated with significantly lower
adjusted likelihood of CDI. Compared to the 0-0.25 occupancy group, patients
admitted on a day of 0.51-0.75 occupancy had 0.86 odds of CDI (95% CI 0.75-0.98).
The 0.76-1.00 admission occupancy group had 0.87 odds of CDI (95% CI 0.75-1.01).
With regard to average occupancy, intermediate levels of occupancy 0.26-0.50
(odds ratio [OR] = 3.04, 95% CI 2.33-3.96) and 0.51-0.75 (OR = 3.28, 95% CI 2.51
4.28) had over 3-fold increased adjusted odds of CDI relative to the low
occupancy group; the high occupancy group did not have signifcantly different
odds of CDI compared to the low occupancy group (OR = 0.96, 95% CI 0.70-1.31).
These findings should prompt exploration of how hospitals react to occupancy
changes and how those care processes translate into hospital-acquired
complications in order to inform best practices.
PMID- 29964277
TI - Pediatric Hospitalist Workload and Sustainability in University-Based Programs:
Results from a National Interview-Based Survey.
AB - Wide variability exists in the clinical workload of pediatric hospitalists
without an accepted standard for benchmarking purposes. By using data obtained
from interviews of pediatric hospital medicine (PHM) program leaders, we describe
the clinical workload of university-based programs and report on the program
sustainability perceived by PHM program leaders. The median clinical hours
reported for a full-time pediatric hospitalist were 1800 hours per year, with a
median of 15 weekends worked per year. Furthermore, program leaders reported an
ideal number of clinical hours as 1700 hours per year. Half of the interviewed
program leaders perceived their current models as unsustainable. Programs
perceived as unsustainable were more likely than those perceived as sustainable
to require a higher number of weekends worked per year or to be university
employed. Further research should focus on establishing benchmarks for the
workloads of pediatric hospitalists and on evaluating factors that can affect
sustainability.
PMID- 29964279
TI - Diagnosing the Treatment.
PMID- 29964278
TI - Impact of Clinical Specialty on Attitudes Regarding Overuse of Inpatient
Laboratory Testing.
AB - Routine laboratory testing is common among hospitalized patients, with associated
harm. Attitudes toward testing and drivers across clinical specialties have not
been described. We performed a cross-sectional study and anonymously surveyed
inpatient clinicians (nurses, advanced practice providers, and physicians) at a
tertiary cancer center regarding attitudes toward unnecessary laboratory testing
and its drivers across clinical specialties. A total of 837 providers completed
surveys (response rate 53%). Most respondents agreed with daily testing of
hospitalized patients and that daily labs generally enhance safety, and those
from pediatric and surgical specialties generally valued testing less than
others. Participants most commonly indentified habit and institutional culture as
important drivers of unnecessary testing. There were differences in other drivers
across specialties, with pediatric clinicians identifying family pressure more
commonly and fear of litigation less commonly compared to others. Future
interventions to reduce unnecessary inpatient laboratory testing should
acknowledge different attitudes based on specialty and tailor interventions
accordingly.
PMID- 29964280
TI - Acoustically-mediated intracellular delivery.
AB - Recent breakthroughs in gene editing have necessitated practical ex vivo methods
to rapidly and efficiently re-engineer patient-harvested cells. Many physical
membrane-disruption or pore-forming techniques for intracellular delivery,
however, result in poor cell viability, while most carrier-mediated techniques
suffer from suboptimal endosomal escape and hence cytoplasmic or nuclear
targeting. In this work, we show that short exposure of cells to high frequency
(>10 MHz) acoustic excitation facilitates temporal reorganisation of the lipid
structure in the cell membrane that enhances translocation of gold nanoparticles
and therapeutic molecules into the cell within just ten minutes. Due to its
transient nature, rapid cell self-healing is observed, leading to high cellular
viabilities (>97%). Moreover, the internalised cargo appears to be uniformly
distributed throughout the cytosol, circumventing the need for strategies to
facilitate endosomal escape. In the case of siRNA delivery, the method is seen to
enhance gene silencing by over twofold, demonstrating its potential for enhancing
therapeutic delivery into cells.
PMID- 29964281
TI - Redox transmetallation approaches to the synthesis of extremely bulky amido
lanthanoid(ii) and -calcium(ii) complexes.
AB - Redox transmetallation protolysis reactions between HgPh2, elemental metals, M =
Ca, Eu, or Yb, and the bulkyl arylsilylamine PhL?H (HN(SiPh3)(Ar?), Ar? =
C6H2Pri{C(H)Ph2}2-4,2,6), or the borylsilylamine PhLBoH (HN(SiPh3){B(DipNCH)2},
Dip = C6H3Pri2-2,6) pro-ligands yielded complexes incorporating doubly
deprotonated, N,C-chelating amido/organyl ligands, viz. [M(L-H) (thf)x]n, L-H =
PhL?-H (1-3) or PhLBo-H (4-5); M = Ca (1, 4), Eu (2) or Yb (3, 5); x = 0 (5) or 2
(1-4); n = 1 (1-4) or 2 (5). Structural differences between 4 and 5 represent a
rare divergence in the chemistry of divalent calcium and ytterbium. Utilisation
of a less hindered bis(aryl) amine, DLMH (HN(Dip)(Mes), Mes = C6H2Me3-2,4,6) in a
similar reaction yielded a three-coordinate, trigonal planar ytterbium complex
[Yb(DLM)2(thf)] (6). Direct redox transmetallation reactions between an amido
mercurial iodide [(MeL?)HgI] (7, MeL? = -N(SiMe3)(Ar?)) and ytterbium or europium
metal afforded homoleptic [Yb(MeL?)2] (8) and heteroleptic [{Eu(MeL?)(MU
I)(thf)}2] (9) respectively. This study highlights the versatility of redox
transmetallation pathways to amido-lanthanoid complexes, especially where such
compounds are difficult to access using conventional salt metathesis pathways.
PMID- 29964282
TI - Recent advances in the annulation of Morita-Baylis-Hillman adducts.
AB - In this review, we summarize some of the most recent advances in the construction
of cyclic compounds from the annulation of Morita-Baylis-Hillman (MBH) adducts,
which have demonstrated their importance by possessing diverse functional groups.
Significant examples including [3 + 2], [3 + 3], [3 + 4] and other cyclizations
described herein with MBH adducts were proven to be efficient approaches for the
preparation of diverse cyclic structure motifs. However, most of the reported
strategies are based on the use of non-chiral catalysts/ligands, whilst
stereoselective reactions remain largely unexplored. This area is still in its
infancy and future research on MBH adducts will definitely benefit the organic
chemistry community, especially for the synthesis of drug candidates and other
molecules that might draw attention to materials sciences.
PMID- 29964284
TI - Suppression of surfaces states at cubic perovskite (001) surfaces by CO2
adsorption.
AB - By using first-principles approach, the interaction of CO2 with (001) surfaces of
six cubic ABO3 perovskites (A = Ba, Sr and B = Ti, Zr, Hf) is studied in detail.
We show that CO2 adsorption results in the formation of highly stable CO3-like
complexes with similar geometries for all investigated compounds. This reaction
leads to the suppression of the surfaces states, opening the band gaps of the
slab systems up to the corresponding bulk energy limits. For most AO-terminated
ABO3(001) perovskite surfaces, a CO2 coverage of 0.25 was found to be sufficient
to fully suppress the surface states, whereas the same effect can only be
achieved at 0.50 CO2 coverage for the BO2-terminated surfaces. The largest band
gap modulation among the AO-terminated surfaces was found for SrHfO3(001) and
BaHfO3(001), whereas the most profound effect among the BO2-terminated surfaces
was identified for SrTiO3(001) and BaTiO3(001). Based on these results and
considering practical difficulties associated with measuring conductivity of
highly resistive materials, TiO2-terminated SrTiO3(001) and BaTiO3(001) were
identified as the most prospective candidates for chemiresistive CO2 sensing
applications.
PMID- 29964283
TI - Silver(i)-catalyzed sequential hydroamination and Prins type cyclization for the
synthesis of fused benzo-delta-sultams.
AB - An intramolecular annulation strategy has been developed for the synthesis of
tetrahydrobenzo[e]pyrano[4,3-c][1,2]thiazine derivatives by means of coupling of
aldehydes with 2-(4-hydroxybut-1-yn-1-yl)-N-arylsulfonamides using a catalytic
amount of silver hexafluoroantimonate in toluene at 80 degrees C. This is the
first report on the synthesis of fused benzo-delta-sultam derivatives through C
N, C-O, and C-C bond formations. The reaction proceeds through a cascade of
hydroamination and Prins type cyclization.
PMID- 29964285
TI - Correlation between piezoelectric and magnetic properties of Fe and Sm co
substituted potassium niobate piezoelectric ceramics.
AB - A piezoelectric material KNbO3 has been co-substituted with the magnetic ions
Sm3+ and Fe3+ in order to explore the relation between piezoelectricity and
magnetism. The samples K1-xSmxNb1-xFexO3 [x = 0.0-0.1] were synthesized using a
solid state reaction route, after estimating the structural stability with the
substitution. Structural studies were employed using XRD with Rietveld refinement
and Raman analysis suggesting Amm2 symmetry. Also, the transition temperature was
observed to change with the increase in Sm and Fe content. This transition
temperature was also confirmed through high temperature XRD and high temperature
Raman results. The dielectric and piezoelectric properties were found to be in
correlation with the intensity of Raman modes for substituted samples, indicating
better ferroelectricity at x = 0.05. A correlation between piezoelectric and
magnetic properties was established in terms of the coercive field and exchange
energy.
PMID- 29964286
TI - First-principles calculations of oxidation potentials of electrolytes in lithium
sulfur batteries and their variations with changes in environment.
AB - Oxidation potentials of electrolyte molecules in Li-sulfur (Li/S) batteries and
their variations in various solvent environments are investigated using first
principles calculations in order to understand oxidative decomposition reactions
of electrolytes for cathode passivation. Electrolyte solvents, Li salts, and
various additives in Li/S batteries along with some Li-ion battery additives are
studied. Oxidation potentials of isolated electrolyte molecules are found to be
out of the operating range of typical Li/S batteries. The complexation of
electrolyte molecules with Li+, salt anion, salt, S8, and pyrene alters oxidation
potentials compared to those of the isolated systems. The salt anion lowers
oxidation potentials of electrolyte molecules by at least 4.7% while the
complexes with Li+ have higher oxidation potentials than the isolated molecules
by at least 10.4%. S8 and pyrene, used as model compounds for sulfur and
sulfur/carbon composite cathode materials, also affect oxidation potentials of
electrolyte molecules, but their influence is negligible and the oxidation trends
differ from those of the Li+ and salt anion. Although complexations change the
oxidation potentials of electrolyte molecules, they are still higher than the
operating voltage range of Li/S batteries, which indicates that oxidation of the
studied electrolytes in Li/S batteries is not expected under ambient conditions.
PMID- 29964287
TI - Reversible solvent-sensitive actuator with continuous bending/debending process
from liquid crystal elastomer-colloidal material.
AB - A reversible solvent-sensitive actuator with a continuous bending/debending
process is fabricated by over-infiltration of liquid crystal monomers into a
colloidal template and subsequent photopolymerization. The fabricated actuator
exhibits a maximum bending angle of 1080 degrees in 1.58 s in dichloromethane,
accompanied with successive debending in 0.32 s. The behavior of the actuator can
be modulated by changing the solvent type, film thickness/length and molar ratio
of A6OCB/C6M. This study will provide an important experimental and theoretical
basis for the development of novel actuators.
PMID- 29964288
TI - Compositional and structural insights into the nature of the H-cluster precursor
on HydF.
AB - Assembly of an active [FeFe]-hydrogenase requires dedicated maturation enzymes
that generate the active-site H-cluster: the radical SAM enzymes HydE and HydG
synthesize the unusual non-protein ligands - carbon monoxide, cyanide, and
dithiomethylamine - while the GTPase HydF serves as a scaffold for assembly of
the 2Fe subcluster containing these ligands. In the current study, enzymatically
cluster-loaded HydF ([2Fe]F) is produced by co-expression with HydE and HydG in
an Escherichia coli host followed by isolation and examination by FTIR and EPR
spectroscopy. FTIR reveals the presence of well-defined terminal CO and CN-
ligands; however, unlike in the [FeFe]-hydrogenase, no bridging CO is observed.
Exposure of this loaded HydF to exogenous CO or H2 produces no significant
changes to the FTIR spectrum, indicating that, unlike in the [FeFe]-hydrogenase,
the 2Fe cluster in loaded HydF is coordinatively saturated and relatively
unreactive. EPR spectroscopy reveals the presence of both [4Fe-4S] and [2Fe-2S]
clusters on this loaded HydF, but provides no direct evidence for these being
linked to the [2Fe]F. Using the chemical reactivity and FTIR data, a large
collection of computational models were evaluated. Their scaled quantum chemical
vibrational spectra allowed us to score various [2Fe]F structures in terms of
their ability to reproduce the diatomic stretching frequencies observed in the
FTIR experimental spectra. Collectively, the results provide new insights that
support the presence of a diamagnetic, but spin-polarized FeI-FeI oxidation state
for the [2Fe]F precursor cluster that is coordinated by 4 CO and 2 CN- ligands,
and bridged to an adjacent iron-sulfur cluster through one of the CN- ligands.
PMID- 29964289
TI - Microporous 2D NiCoFe phosphate nanosheets supported on Ni foam for efficient
overall water splitting in alkaline media.
AB - The development of high-performance non-precious electrocatalysts for both H2 and
O2 evolution reactions (HER and OER activities) and overall water splitting is
highly desirable but remains a grand challenge. Herein, we report a facile method
to synthesize ultrathin, amorphous, porous, oxygen and defect enriched NiCoFe
phosphate nanosheets (NSs). Owing to their microporous confinement in a 2D
orientation, which can reduce the ion transport resistance during electrochemical
processes, and defect enriched structure with higher electrochemically active
surface area, these NiCoFe phosphate porous nanosheets supported on nickel foam
(NiCoFe phosphate NSs/NF) facilitate the diffusion of gaseous products (H2 and
O2) and exhibit remarkable catalytic performance and outstanding stability for
both HER, OER and overall water splitting in an alkaline electrolyte (1.0 M KOH).
For the OER electrocatalyst, 2D NiCoFe phosphate NSs/NF was oxidized to NiCoFe
oxides/hydroxides on the catalyst surface and exhibited remarkable OER activity
with a low overpotential of only 240 mV needed to reach a current density of 10
mA cm-2. For HER, 2D NiCoFe phosphate NSs/NF afforded a current density of 10 mA
cm-2 at a low overpotential of only -231 mV. Furthermore, employing 2D NiCoFe
phosphate NSs/NF as the electrocatalyst for both the anode and the cathode, a
water splitting electrolyzer was able to reach 10 mA cm-2 at a cell voltage of
1.52 V with robust durability. Various characterization techniques indicated that
the long term stability and the activity for overall water splitting are due to
the porosity, the electrochemically active constituents, and synergistic effects.
This work could be inspiring in the design of Earth abundant and highly efficient
electrocatalysts for overall water splitting, especially for OER.
PMID- 29964290
TI - A bromo-capped diruthenium(i,i) N-heterocyclic carbene compound for in situ
bromine generation with NBS: catalytic olefin aziridination reactions.
AB - A bromo-capped metal-metal bonded diruthenium(i,i) complex Ru2(CO)4(PIN)2Br2 (1)
(PIN = 1-isopropyl-3-(5,7-dimethyl-1,8-naphthyrid-2-yl)imidazol-2-ylidene)
generates bromine with N-bromosuccinimide (NBS) at room temperature. Cycloalkene
and stilbene are readily brominated by stoichiometric reactions with 1 and NBS.
An analysis of the dibrominated products suggests the formation of cyclic
bromonium intermediates indicating in situ Br2 generation. Complex 2, an iodide
analogue of 1, is also synthesized. The reaction of 2 with N-iodosuccinimide
releases I2, which is confirmed by the starch-iodine test. The catalytic utility
of 1 is examined for the bromination of phenol. Catalyst 1, in combination with
NBS and base, exhibits regioselectivity towards monobrominated products.
Furthermore, efficient olefin aziridination is demonstrated utilizing catalyst 1
in the presence of NBS, K2CO3 and TsNH2.
PMID- 29964291
TI - Look before you SPRINT: look at the data and look at the consequences.
PMID- 29964292
TI - Excipients: not so inert? When the excipient plays the role of an active
substance, as exemplified by systemic lupus.
AB - It is well recognised that the historical timeline required for developing a
drug, beginning with target identification and validation, is long and often
tedious. It requires a large set of competences in various areas of molecular and
cellular biology, chemistry, pharmacology, imaging, and model animal
experimentation. Once the active molecule appears to be ready for human testing
in controlled clinical trials, then the question arises of how to formulate it to
render it stable, adequately packaged, according to the chosen route of
administration, and bioavailable to reach its target in the affected organs.
Historically, excipients have been considered inert and devoid of medicinal
effect or influence. In fact, excipients are seldom neutral and some of them have
been found to play a significant role, for example by initiating or participating
in chemical and physical interactions with the active substance, leading in
certain cases to compromise its therapeutic activity. It is difficult today to
appreciate the number of potential drugs that have been discarded as a result of
limited efficacy due to inappropriate excipients. This matter is presented here,
with the peptide P140 (LupuzorTM) as example. Two formulations of P140, differing
in the excipients used (mannitol or trehalose), have been evaluated in patients
affected by systemic lupus erythematosus in two successive phase IIb clinical
trials. P140 was shown to reduce excessive autophagy activity discovered in some
lupus immune cell subsets. One of the two excipients, namely trehalose, has been
claimed to exert an intrinsic stimulating activity on autophagy process, which
was found therefore to counteract the beneficial peptide effects.
PMID- 29964293
TI - Subanesthetic ketamine reverses neuronal and astroglial metabolic activity
deficits in a social defeat model of depression.
AB - Depression is one of the most debilitating neuropsychiatric disorders. Most of
the current antidepressants have long remission time and low recovery rate. This
study explores the impact of ketamine on neuronal and astroglial metabolic
activity in prefrontal cortex in a social defeat (SD) model of depression.
C57BL/6 mice were subjected to a social defeat paradigm for 5 min a day for 10
consecutive days. Ketamine (10 mg/kg, intraperitoneal) was administered to mice
for two consecutive days following the last defeat stress. Mice were infused with
[1,6-13 C2 ]glucose or [2-13 C]acetate to assess neuronal and astroglial
metabolic activity, respectively, together with proton-observed carbon-edited
nuclear magnetic resonance spectroscopy in prefrontal cortex tissue extract. The
13 C labeling of amino acids from glucose and acetate was decreased in SD mice.
Ketamine treatment in SD mice restored sucrose preference, social interaction and
immobility time to control values. Acute subanesthetic ketamine restored the 13 C
labeling of brain amino acids from glucose as well as acetate in SD mice to the
respective control values, suggesting that rates of neuronal and astroglial
tricarboxylic acid (TCA) cycle and neurotransmitter cycling were re-established
to normal levels. The finding of improved energy metabolism in SD mice suggests
that fast anti-depressant action of ketamine is linked with improved
neurotransmitter cycling.
PMID- 29964294
TI - Vaginal leiomyoma in a chinchilla (Chinchilla Laniger).
PMID- 29964295
TI - Intense White Molecular Fluorescence from Naphthoxazole-Quinoline Derivatives.
AB - Naphthoxazole derivatives are small heterocyclic compounds endowed with
outstanding fluorescence properties. In this work, we report a detailed study of
the intense white light fluorescence observed in naphthoxazole-quinoline dyads in
solvent mixtures including at least a strong hydrogen bonding solvent. The same
phenomenon was also studied in inclusion complexes naphthoxazole derivatives
sulfonated-betaCD either in aqueous solution as well as in solid phase. A novel
mechanism of white molecular fluorescence generation based on solvent-to
fluorophore proton transfer facilitated by ground state hydrogen bonding was
characterized. The emission combines both, a blue charge transfer fluorescence
emitted by the locally excited singlet state along with a red-shifted emission
from a proton transfer complex.
PMID- 29964296
TI - Astrocytes in juvenile neuronal ceroid lipofuscinosis (CLN3) display metabolic
and calcium signaling abnormalities.
AB - Juvenile neuronal ceroid lipofuscinosis (JNCL) is a lysosomal storage disease
caused by autosomal recessive mutations in ceroid lipofuscinosis 3 (CLN3).
Children with JNCL experience progressive visual, cognitive, and motor
deterioration with a decreased life expectancy (late teens-early 20s). Neuronal
loss is thought to occur, in part, via glutamate excitotoxicity; however, little
is known about astrocyte glutamate regulation in JNCL. Spontaneous Ca2+
oscillations were reduced in murine Cln3Deltaex7/8 astrocytes, which were also
observed following glutamate or cytokine exposure. Astrocyte glutamate transport
is an energy-demanding process and disruptions in metabolic pathways could
influence glutamate homeostasis in Cln3Deltaex7/8 astrocytes. Indeed, basal
mitochondrial respiration and ATP production were significantly reduced in
Cln3Deltaex7/8 astrocytes. These changes were not attributable to reduced
mitochondria, since mitochondrial DNA levels were similar between wild type and
Cln3Deltaex7/8 astrocytes. Interestingly, despite these functional deficits in
Cln3Deltaex7/8 astrocytes, glutamate transporter expression and glutamate uptake
were not dramatically affected. Concurrent with impaired astrocyte metabolism and
Ca2+ signaling, murine Cln3Deltaex7/8 neurons were hyper-responsive to glutamate,
as reflected by heightened and prolonged Ca2+ signals. These findings identify
intrinsic metabolic and Ca2+ signaling defects in Cln3Deltaex7/8 astrocytes that
may contribute to neuronal dysfunction in CLN3 disease.
PMID- 29964297
TI - P53 mediates lipopolysaccharide-induced inflammation in human gingival
fibroblasts.
AB - BACKGROUND: The role of reactive oxygen species (ROS) in activation of the
inflammatory response has been proven in previous study using human gingival
fibroblasts (HGFs) to lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg)
stimulation, but its exact mechanism has not been established. ROS can be
generated through increased oxidative phosphorylation. P53 originally identified
as a tumor suppressor, has been demonstrated to be associated with energy
metabolism. We proposed that LPS-induced inflammatory cytokines release in HGFs
is mediated by interaction between P53 and ROS levels. METHODS: HGFs were grown
in medium with Pg LPS stimulation. Gene expression was performed by quantitative
reverse transcription polymerase chain reaction (qRT-PCR) and Western blot
analysis. HGFs were also processed by immunofluorescence to characterize the
localization of P53. ROS was measured using a multimodal microplate reader and
immunofluorescence microscopy. Cellular respiration levels were performed with a
high-resolution respirometer. Cytokines secretion was confirmed by enzyme-linked
immunosorbent assay. RESULTS: LPS-induced P53 activity and localization in
mitochondria led to cellular redox imbalance and mitochondrial dysfunction, thus
triggered the cellular inflammatory response with increased secretion of
interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha. Furthermore,
the cellular redox imbalance and inflammation induced by LPS were reversed by
inhibiting P53 activity. P53 expression followed by LPS-induced inflammation was
also be restricted by suppressing ROS generation. CONCLUSIONS: The present study
shows that LPS-induced inflammation in HGFs is partially dependent on P53
modulating ROS and ROS stimulating P53, which suggests that P53 and ROS may form
a feedback loop. The identification of this mechanism may provide potential new
therapeutic strategies for periodontitis.
PMID- 29964298
TI - How midwives manage rapid pre-loading of fluid in women prior to low dose
epidurals: A retrospective chart review.
AB - AIM: To describe contemporary routine practice regarding rapid pre-loading of
intravenous fluid management prior to epidural analgesia during labour and birth.
BACKGROUND: Midwives are the key health professionals providing care for women
before, during and after an epidural in labour. Part of this management involves
maternal hydration; however, how midwives assess and manage maternal hydration
and fluid management is not well understood. Prior to the administration of a low
dose epidural for pain relief a rapid intravenous pre-loading of between 500-1000
mls of crystalloid fluids is administered to the pregnant women. Currently, there
is limited evidence available to assess if intravenous pre-loading reduces
maternal hypotension and foetal bradycardia. Anecdotal evidence suggests that
wide variation in clinical practice in relation to volume of fluid administered,
fluid status assessment and clinical documentation occurs. DESIGN: A
retrospective medical health record review, in a regional Australian maternity
hospital. METHODS: A retrospective medical health record review chart review from
women who received an epidural for pain relief during labour and birth (June
September 2015). RESULTS: Data from 293 charts were collected, including:
maternal factors; blood pressure distributions; maternal fluid status; types,
concentration and timing of analgesia loading doses; IV fluid loading volumes;
maternal hypotension, foetal outcomes and documentation of fluid balance charts.
Wide variation in clinical practice was evident with midwives administering pre
loading fluid volumes ranging from 250-1000 ml. Midwifery assessment,
documentation and practice pertaining to hydration was inconsistent and lacking.
CONCLUSION: Management of intravenous fluids during labour is fragmented.
Although fluid balance charts are used internationally to assess maternal
hydration, documentation of fluid balance status was poor. Multi-professional
collaboration between obstetrics, anaesthetics and midwifery is required to
address this wide variation and reach consensus on best practice based on what
evidence is currently available.
PMID- 29964301
TI - Immunohistochemical analysis of neutrophils, interleukin-17, matrix
metalloproteinase-9, and neoformed vessels in oral squamous cell carcinoma.
AB - BACKGROUND: Tumor-associated neutrophils (TAN), matrix metalloproteinase-9 (MMP
9), interleukin-17 (IL-17), and angiogenesis have been proposed as prognostic
biomarkers of malignant tumors. The purpose of this study was to investigate
these inflammatory markers as prognostic factors for oral squamous cell carcinoma
(OSCC). METHODS: Specimens of OSCC (n = 30), healthy oral mucosa (negative
control, n = 10), oral leukoplakia (n = 10), and apical granuloma with abscess
(positive inflammatory controls, n = 10) were immunostained for CD66b
(neutrophils), MMP-9, IL-17, and CD105 (neoformed microvessels). Semiquantitative
(IL-17) and quantitative (CD66b, IL-17, MMP-9, and CD105) analyses were
performed. Clinical information (TNM stage, metastasis, recurrence, and survival)
and tumor histological grade were also obtained. RESULTS: Positivity for TAN, MMP
9, IL-17, and CD105 was higher in OSCC than in the negative control (P < 0.05)
and oral leukoplakia, but similar to the positive inflammatory control.
Coincident high counts of inflammatory markers (CD66b, MMP-9, IL-17, and CD105)
were associated with lymph node metastasis of OSCC. Associations between high
numbers of neoformed microvessels and advanced clinical stage and a higher degree
of malignancy were also demonstrated. CONCLUSIONS: Combined positivity for TAN,
MMP-9, IL-17, and CD105 appears to be associated with the metastasis-prone
phenotype of OSCC.
PMID- 29964299
TI - Catechol derived from aronia juice through lactic acid bacteria fermentation
inhibits breast cancer stem cell formation via modulation Stat3/IL-6 signaling
pathway.
AB - Cancer stem cells (CSCs) as a subpopulation of cancer cells are drug-resistant
and radiation-resistant cancer cells to be responsible for tumor progress,
maintenance and recurrence of cancer, and metastasis. This study isolated and
investigated a new cancer stem cell (CSC) inhibitor derived from lactic acid
fermentation products using culture broth with 2% aronia juice. The anti-CSC
activity of aronia-cultured broth was significantly higher than that of the
control. Activity-guided fractionation and repeated chromatographic preparation
led to the isolation of one compound. Using nuclear magnetic resonance and ESI
mass spectrometry, we identified the isolated compound as catechol. In this
study, we report that aronia-fermented catechol has a novel inhibitory effect on
human breast CSCs. Catechol inhibited breast cancer cell proliferation and
mammosphere formation in a dose-dependent manner. This compound reduced the
CD44high /CD24low subpopulation, ALDH-expressing cell population and the self
renewal-related genes nanog, sox2, and oct4. Catechol preferentially reduced mRNA
transcripts and protein levels of Stat3 and did not induce c-Myc degradation.
These findings support the novel utilization of catechol for breast cancer
therapy via the Stat3/IL-6 signaling pathway. Our results suggest that catechol
can be used for breast cancer therapy and that Stat3 expression is a marker of
CSCs. Catechol inhibited Stat3 signaling by reducing Stat3 expression and
secreted IL-6, a CSC survival factor. These findings support the novel
utilization of catechol for breast cancer therapy via Stat3/IL-6 signaling.
PMID- 29964302
TI - Tai chi and yoga in residential aged care: Perspectives of participants: A
qualitative study.
AB - AIMS AND OBJECTIVES: This qualitative study examined the appropriateness and
acceptability of 14-week modified tai chi and yoga programmes in an Australian
residential aged care (RAC) setting by exploring experiences and perspectives of
frail older residents and staff participants. BACKGROUND: Older persons in RAC
have limited opportunities for physical activity. Tai chi and yoga are
mindfulness-based exercise interventions that have been used to promote physical
and psychological health of older adults in community settings. While research on
tai chi and yoga interventions in community settings is promising, there is
limited research regarding the interventions' appropriateness and acceptability
for frail older residents in residential care settings in Australia. DESIGN:
Descriptive and qualitative component of a mixed-methods study. METHODS: All
residents who participated in the modified yoga and tai chi interventions and
staff who supported them were invited. A total of 19 individuals comprising 16
residents and three staff members participated in three focus group interviews.
The interviews were audio-recorded, transcribed and analysed thematically using a
qualitative descriptive approach. RESULTS: Nine themes that reflected the
uniqueness of the programmes' mind-body approach are presented: (a) novel, new
and exciting; (b) smoothness, rhythm and flow; (c) slow and mindful; (d) gentle
but rewarding; (e) moving whole body; (f) perceived benefits; (g) worthwhile; (h)
feeling alive; and (i) calming and relaxing. CONCLUSIONS: The modified programmes
of tai chi and yoga was acceptable, appropriate, enjoyable and helpful. Both tai
chi and yoga appear to provide appropriate physical exercise and opportunities
for older persons to enhance their quality of life through interaction of
physical, emotional and intellectual wellness domains. RELEVANCE TO CLINICAL
PRACTICE: The 14-week modified programmes of tai chi and yoga could be applied to
frail older RAC population to promote health and active ageing.
PMID- 29964304
TI - Elucidation of chemical modifier reactivity towards peptides and proteins and the
analysis of specific fragmentation by matrix-assisted laser desorption/ionization
collision-induced dissociation tandem mass spectrometry.
AB - RATIONALE: Matrix-assisted laser desorption/ionization mass spectrometry (MALDI
MS) analysis of covalent 5-lipoxygenase inhibitors is challenging due to unknown
amino acid specificity and low posttranslational modification (PTM)
identification rates. The analysis of the amino-acid specificity and of the
characteristic fragmentation of chemically modified peptides is considered to
improve knowledge for the analysis of chemically modified peptides and proteins
by MALDI-MS. METHODS: Various compounds were used to investigate the modification
of synthetic peptides carrying reactive amino acid residues. Mass spectra were
recorded using a MALDI-LTQ Orbitrap XL for high-resolution mass spectrometry and
ion trap MALDI-MS2 . UV-Vis-based reduction and radical scavenging analysis was
conducted. The on-plate digestion method described by Ruhl et al was utilized for
modification-site analysis at 5-lipoxygenase. RESULTS: The analysis of amino-acid
specific reactivity revealed the reactivity of quinones towards cysteine residues
and the potential occurrence of a subsequent oxidative process was observed by an
UV-Vis-based reduction assay. MALDI collision-induced dissociation tandem mass
spectrometry (CID-MS2 ) indicated a prominent fragmentation mechanism of modified
cysteine and histidine residues. Fragmentation included highly abundant neutral
loss signals which could be used to identify new modifications induced by
chemical modifiers at the cysteine-159 residue of 5-lipoxygenase. CONCLUSIONS:
Specificity and fragmentation analysis provides crucial information for the
analysis of chemically modified cysteines and histidines by MALDI-MS. Elucidation
of binding sites by MALDI-MS has been significantly improved using an easy-to-run
peptide assay and gives background information for the analysis in the case of
chemically modified 5-lipoxygenase.
PMID- 29964303
TI - Simultaneous determination of tobacco minor alkaloids and tobacco-specific
nitrosamines in mainstream smoke by dispersive solid-phase extraction coupled
with ultra-performance liquid chromatography/tandem orbitrap mass spectrometry.
AB - RATIONALE: The minor alkaloids in tobacco play an important role in the chemical
composition of cigarette smoke, and they are precursors of tobacco-specific
nitrosamines (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N
nitrosonornicotine (NNN), N-nitrosoanabasine (NAB) and N-nitrosoanatabine (NAT)).
NNN and NNK are classified as group 1 carcinogens. A method quantitating both
tobacco minor alkaloids and tobacco-specific nitrosamines in mainstream smoke has
not been reported. METHODS: Tobacco minor alkaloids and tobacco-specific
nitrosamines in cigarette mainstream smoke were extracted by sonication. The
extract was cleaned up by dispersive solid-phase extraction, and separation was
achieved via ultra-performance liquid chromatography/tandem orbitrap mass
spectrometry. RESULTS: The method was validated by analysis of six replicate
samples spiked with three levels of the analyses. The mean recoveries for the six
replicates were from 84.7% to 118% with less than 15% relative standard deviation
except myosmine at the low spiked level and the calculated detection limits were
0.066 to 13.2 ng/cig, respectively. The mean concentrations of nicotyrine,
anabasine, nornicotine, anatabine, myosmine, 2,3-bipyridine, cotinine,
nicotelline, N-formylnornicotine, NNK, NNN, NAB and NAT in 30 different brands of
commercial cigarette smoke under the ISO smoking regimen were 2.50 MUg/cig, 2.34
MUg/cig, 3.21 MUg/cig, 5.78 MUg/cig, 2.83 MUg/cig, 1.05 MUg/cig, 1.55 MUg/cig,
0.55 MUg/cig, 2.48 MUg/cig, 6.06 ng/cig, 3.62 ng/cig, 0.40 ng/cig and 6.15
ng/cig, respectively. CONCLUSIONS: The proposed method was suitable for analysis
of tobacco minor alkaloids and tobacco-specific nitrosamines in cigarette
mainstream smoke.
PMID- 29964305
TI - Encouraging interprofessional collaboration: The effects of clinical protocols.
AB - AIMS AND OBJECTIVES: To consider the characteristics of protocol documents
themselves as a factor influencing the nature of care delivery and their
potential to facilitate greater interprofessional collaboration. BACKGROUND:
Healthcare guidelines and clinical protocols provide important guidance and
direction to health professionals in their delivery of care. By detailing
requirements and actions to be taken in specified circumstances or contexts,
these documents may facilitate a broadening of the pool of people able to deliver
care. DESIGN: Critical reading of four clinical protocols representing the range
of protocol types in use was carried out to consider the extent to which the
documentation of guidelines and protocols and the documents themselves might be
considered as vehicles for increased collaboration in health care. METHODS: A
"close reading" rubric was developed directing the researcher to look for
evidence in each protocol of the following: authorship, person or group
responsible for the protocol's development; stated document purpose; target
readers, either stated or implied; the particular subjects, the document names
and the objects created by them such as care pathways; the use of specific
terminology and imagery, the documents' form and structure; and evidence of
intertextuality referring to other documents, for example legislation or policy
statements. Tabulation of the coding analysis is presented. RESULTS: Nurses were
the only professional group named in the documents as assignees or subjects.
"Patients" and "care" are the objects created, and the scientific-biomedical
discourse with its associated procedural language was dominant. CONCLUSIONS: Many
protocols have been developed to standardise practice and increase the
effectiveness of teamwork. They may, however, constrain collaboration in
healthcare settings because they diminish a nursing "voice" and create the
expectation that nurses alone work across the spectrum of protocols. RELEVANCE TO
CLINICAL PRACTICE: An unintended consequence of the global use of clinical
protocols and guidelines to support safe and efficient healthcare delivery may be
to reduce interprofessional collaboration.
PMID- 29964306
TI - Asynchronous rhythms of circulating conjugated and unconjugated bile acids in the
modulation of human metabolism.
AB - BACKGROUND AND OBJECTIVES: Bile acids (BAs) traversing the enterohepatic
circulation (EHC) influence important metabolic pathways. By determining
individual serum BAs in relation to markers of metabolic activity, we explored
how diurnal variations in their EHC relate to hepatic metabolism in normal
humans. METHODS: Serum BAs, fibroblast growth factor 19 (FGF19), lipoproteins,
glucose/insulin and markers of cholesterol and BA syntheses were monitored for 32
h in 8 healthy males. Studies were conducted at basal state and during initiation
of cholestyramine treatment, with and without atorvastatin pretreatment. Time
series cross-correlation analysis, Bayesian structural model and Granger
causality test were applied. RESULTS: Bile acids synthesis dominated daytime, and
cholesterol production at night. Conjugated BAs peaked after food intake, with
subsequent FGF19 elevations. BA synthesis was reduced following conjugated BA and
FGF19 peaks. Cholestyramine reduced conjugated BAs and FGF19, and increased BA
and cholesterol production; the latter effects attenuated by atorvastatin. The
relative importance of FGF19 vs. conjugated BAs in this feedback inhibition could
not be discriminated. Unconjugated BAs displayed one major peak late at
night/early morning that was unrelated to FGF19 and BA synthesis, and abolished
by cholestyramine. The normal suppression of serum triglycerides, glucose and
insulin observed at night was attenuated by cholestyramine. CONCLUSIONS:
Conjugated and unconjugated BAs have asynchronous rhythms of EHC in humans.
Postprandial transintestinal flux of conjugated BAs increases circulating FGF19
levels and suppresses BA synthesis. Unconjugated BAs peak late at night,
indicating a non-postprandial diurnal change in human gut microflora, the
physiological implications of which warrants further study.
PMID- 29964307
TI - Relatives' strategies in subacute brain injury rehabilitation: The warrior, the
observer and the hesitant.
AB - BACKGROUND: Relative involvement is crucial in rehabilitation when patients are
incapable of being involved due to cognitive and functional dysfunction. However,
studies have shown that this is complex because of differing understandings of
the meaning of involvement as well as diverse needs to be involved. AIMS AND
OBJECTIVES: To explore the experience of the rehabilitation process from the
perspectives of relatives of patients with a traumatic brain injury. The aim of
the study was, through a theoretical-empirical analysis, to identify relatives'
strategies and practices in the rehabilitation process as evidenced in meetings
with providers. DESIGN: A longitudinal study with a qualitative approach, drawing
on the theory of Pierre Bourdieu. METHODS: Data were generated using participant
observation and semi-structured interviews. Participants were eleven relatives of
patients with a severe traumatic brain injury, followed through in-patient
rehabilitation varying from 9-12 weeks. Analysis was undertaken using both an
inductive and deductive approach. FINDINGS: Drawing on Bourdieu's concept of
strategy, three relative positions were identified, the warrior, the observer and
the hesitant. These positions illustrate how different relative positions and
their related dispositions influence the strategies used by relatives of patients
with a severe traumatic brain injury evidenced in how they act, participate and
relate to both the patient and the providers during the course of rehabilitation.
CONCLUSIONS: Acknowledging the relatives' positions during the rehabilitation
process enables better understanding and support of the relatives in the
rehabilitation process to meet their (and thus the patients') diverse needs.
RELEVANCE TO CLINICAL PRACTICE: The findings have practical implications in
informing how clinicians meet, interact, communicate and involve relatives of
adult patients' with traumatic brain injury in decision-making during
rehabilitation.
PMID- 29964308
TI - Development of a method for the determination of 8-iso-PGF2alpha in sheep and
goat plasma using solid-phase microextraction and ultra-performance liquid
chromatography/tandem mass spectrometry.
AB - RATIONALE: Isoprostane 8-iso-PGF2alpha is a biomarker of lipid peroxidation in
cell membranes. The method developed to measure plasma total levels (esterified +
free) of 8-iso-PGF2alpha must be reproducible and be able to reduce the use of
solvents in solid phase extraction. It should be useful to evaluate oxidative
stress due to the excess of free radicals that are generated by some disorder or
disease. METHODS: The method was developed using solid-phase microextraction with
Oasis(r)MAX MUElution plates and ultra-performance liquid chromatography/tandem
mass spectrometry (UPLC/MS/MS). Electrospray ionization was performed in the
negative mode (ESI-); the multiple reaction monitoring mode (MRM) was used. The
development of the method included the optimization of the chromatographic
conditions to achieve the separation of PGF2alpha and 8-iso-PGF2alpha as well as
the optimization of the microextraction conditions of the analyte of interest in
ovine and goat plasma. RESULTS: The developed method was validated with a
calibration curve of plasma samples fortified with standards at five
concentration levels in the range 49-639 pg/mL. The average recovery was 89% with
a standard deviation of 10.73%. The inter-day precision was evaluated, obtaining
a coefficient of variance (CV) less than 15%. The limit of quantification was 20
pg/mL and the limit of detection was 10 pg/mL. 8-iso-PGF2a was determined in the
plasma of 14 sheep and 20 goats of 5 months of age and 6 goats of 24 months of
age. The concentrations found were 50-300 pg/mL. CONCLUSIONS: The method
developed is precise, accurate and reliable with low reagent consumption compared
with conventional solid-phase extraction. The analysis time was decreased
because, with the use of the microextraction plate, the step of the evaporation
and reconstitution of the analyte was avoided. The method is applicable to
quantify the plasma total levels (esterified + free) of 8-iso-PGF2alpha.
PMID- 29964309
TI - Factors moderating the mutual impact of benefit finding between Chinese patients
with cancer and their family caregivers: A cross-sectional study.
AB - OBJECTIVE: With growing recognitions of the significance of benefit finding (BF)
in cancer practice, research has increased to explore factors that may influence
BF in the cancer context. Few studies have focused explicitly on factors
influencing BF from the dyadic perspective of cancer patient (CP)-family
caregiver (FC) dyads. The objectives of the study were to examine BF relationship
between CPs and FCs and to investigate factors that may modify the BF
relationships between CPs and FCs. METHODS: Participants consisted of 772 dyads
of CPs and FCs. Three types of variables were collected as potential modifying
factors, including CP-related variables, FC-related variables, and psychological
related variables. Descriptive statistics, T test, Pearson correlations, and
subgroup analysis were applied to conduct the data analysis. RESULTS: Cancer
patients and FCs experienced similar moderate to high BF ranging from 65% to 81%,
with the exception of acceptance, in that CPs had higher levels of acceptance
than did FCs (P < .05). Various factors modifying the BF relationships between
CPs and FCs were identified, including dyads' gender, marital status, education
level, employment status, level of being informed about the disease, and cancer
type and treatment, anxiety, depression, and self-efficacy. CONCLUSIONS: Study
findings call attention to the BF, as well as related factors, from the dyadic
perspective of CP-FC dyads. Health care professionals need to include FCs of the
CPs in their care and provide them with support, to encourage the CP-FC dyads to
share their experience and improve BF together, and to develop a dyadic-based
intervention program to help enhancing dyads BF.
PMID- 29964310
TI - eHealth versus equity: Using a feminist poststructural framework to explore the
influence of perinatal eHealth resources on health equity.
AB - AIMS AND OBJECTIVES: To explore whether and how eHealth resources targeted to
families during the perinatal period effectively reach a diverse population or
further oppress marginalised groups. BACKGROUND: eHealth is often intended to
reach a broad population, thus health content must be relatively generalised
which limits the ability to tailor health education and interventions to
individual needs. Generalisation of health information has historically
represented a hegemonic depiction of the health consumer, especially within the
perinatal period, often disregarding the diversity that exists in the world and
perpetuating heteronormative constructs within healthcare systems as a result.
DESIGN: A critical review of the literature regarding perinatal eHealth resources
was conducted using a feminist poststructuralist approach for analysis. Included
literature addresses the development, implementation and/or evaluation of
perinatal eHealth resources. DISCUSSION: This approach uncovered hegemonic
discourses related to the current state of perinatal eHealth resources. Nurses
and midwives have the unique advantage of interacting and understanding diverse
populations. Thus, nurses and midwives are integral to the development,
implementation and evaluation of eHealth resources to reduce social health
inequity. RELEVANCE TO CLINICAL PRACTICE: This paper acts as an exemplar on how
to apply feminist poststructuralism to highlight inequities that exist and
identifies strategies for nurses and midwives to become involved in the
development of eHealth resources or advocate for greater visibility within
current resources.
PMID- 29964311
TI - The dilemma of patient safety work: Perceptions of hospital middle managers.
AB - Patient safety continues to be a challenge for health care. Medical errors are
not decreasing but continue to show roughly the same patterns in Sweden and other
Western countries. This interview study aims to explore how 27 hospital middle
managers responsible for patient safety work in a Swedish university hospital
perceive this task. A qualitative analysis was performed. A code template was
created, and each code was explored in depth and summarized into six categories.
We conclude that patient safety work appears to have low priority; hospital top
management does not seem to have any real interest in patient safety; incidents
are underreported; and the organization of patient safety work seems to be
insufficient and carried out insofar as resources are available. These parameters
may explain why medical errors remain on a certain level and do not seem to
decrease in spite of various support programs.
PMID- 29964312
TI - Feasibility of concomitant vacuum-assisted removal of lead-related vegetations
and cardiac implantable electronic device extraction.
AB - BACKGROUND: Cardiac implantable electronic device (CIED) infections associated
with large, mobile vegetation adds to the complexity of lead extraction and is
associated with significant patient morbidity and mortality. OBJECTIVE: To show
the feasibility of concomitant cardiovascular implantable electronic device
extraction and vacuum-assisted removal of lead-related vegetations. METHODS: This
is a single-center retrospective case series of consecutive patients with
persistent bacteremia, sepsis, or endocarditis despite medical therapy who have
vegetations >2 cm and subsequently underwent immediate CIED lead extraction after
debulking with vacuum-assisted suction. RESULTS: Eight patients underwent
successful removal of 17 leads immediately after debulking of vegetations with
vacuum-assisted device suction. Debulking procedure was not successful in 1
patient due to inability to direct the vacuum suction device into proper
position. There were no intraprocedure complications related to the vacuum
assisted debulking. One patient required open sternotomy for tear of the coronary
sinus ostium related to extraction of a left ventricular pacing electrode. There
was no mortality within 30 days of the procedure. CONCLUSIONS: Based upon these
clinical results, it is feasible for patients with infected CIED systems that
have large right-sided vegetations to undergo vacuum-assisted debulking then
immediately followed by percutaneous CIED removal in whom surgical removal is
considered high risk.
PMID- 29964314
TI - Theoretical Estimation of Optimal Parameters for Maximum Fluorescence under
Pulsed Excitation.
AB - We present a detailed theoretical study on choosing optimum excitation parameters
for maximizing the fluorescence yield. Using a model system, we show how the time
averaged emission (fluorescence) is modulated as the excitation conditions are
changed from continuous wave excitation to pulsed excitation with various
combinations of pulse widths and pulse repetition-rates for the same time
averaged excitation intensity. We conclude that depending on the excitation
intensity, different pulse parameters are required for generating maximum
fluorescence output. Our method can be implemented for other more sophisticated
models without much difficulty.
PMID- 29964313
TI - CYP450-mediated mitochondrial ROS production involved in arecoline N-oxide
induced oxidative damage in liver cell lines.
AB - BACKGROUND: IARC has classified the betel nut as a human environmental
carcinogen. Previous studies have found that arecoline (AR) is the major alkaloid
present in the saliva of betel quid chewers. Saliva contains a large content of
AR which has been further shown to cause mutation of oral mucosa cells, resulting
in oral cancer. Whereas, to date, there are only few studies reported the
hepatotoxicity associated with arecoline and betel nut chewing. Therefore, the
main purpose of this study was to determine the toxic effects of AR and its
oxidative metabolite, arecoline N-oxide (ARNO), in normal liver cell lines.
METHODS: The cytotoxic, genotoxic, and mutagenic effects were detected by crystal
violet staining, alkaline comet assay, and Salmonella mutagenicity test,
respectively. Measurement of intracellular reactive oxygen species (ROS)
generation was determined using the H2-DCFDA assay. RESULTS: Our results
demonstrated that ARNO exerted higher cytotoxicity, DNA damage, and mutagenicity
than its parent compound arecoline in liver cells. Antioxidants, such as N
acetylcysteine, Trolox, and penicillamine, strongly protected liver cells from
ARNO-induced DNA damage and ROS production. Furthermore, co-treatment with Mito
TEMPO also effectively blocked ARNO-induced ROS production in liver cells.
Besides antioxidants, co-treatment with 1-aminobenzotriazole and methimazole
nearly completely suppressed ARNO-induced ROS production in liver cells.
CONCLUSIONS: Our data suggest that arecoline ingested from the habit of chewing
betel quid can be primarily oxidized to ARNO, thereby enhancing its toxicity
through increased ROS production. Considering the excellent protective effects of
both mitochondria-targeted antioxidant and CYP450 inhibitor on ARNO-induced ROS
production in liver cells, mitochondria CYP450-mediated metabolism of ARNO may be
a key mechanism. Collectively, our results provide novel cellular evidence for
the positive connection between habitual betel quid chewing and the risk for
liver damage.
PMID- 29964315
TI - Molecular Ruby under Pressure.
AB - The intensely luminescent chromium(III) complexes [Cr(ddpd)2 ]3+ and [Cr(H2
tpda)2 ]3+ show surprising pressure-induced red shifts of up to -15 cm-1 kbar-1
for their sharp spin-flip emission bands (ddpd=N,N'-dimethyl-N,N'-dipyridine-2-yl
pyridine-2,6-diamine; H2 tpda=2,6-bis(2-pyridylamino)pyridine). These shifts
surpass that of the established standard, ruby Al2 O3 :Cr3+ , by a factor of 20.
Beyond the common application in the crystalline state, the very high quantum
yield of [Cr(ddpd)2 ]3+ enables optical pressure sensing in aqueous and
methanolic solution. These unique features of the molecular rubies [Cr(ddpd)2 ]3+
and [Cr(H2 tpda)2 ]3+ pave the way for highly sensitive optical pressure
determination and unprecedented molecule-based pressure sensing with a single
type of emitter.
PMID- 29964316
TI - White matter measures correlate with essential tremor severity-A pilot diffusion
tensor imaging study.
AB - BACKGROUND: An evolving pathophysiological concept of essential tremor (ET)
points to diffuse brain network involvement, which emphasizes the need to
investigate white matter (WM) changes associated with motor symptoms of ET.
OBJECTIVES: To investigate ET-related WM changes and WM correlates of tremor
severity using tremor clinical rating scales and accelerometry. METHODS: Tract
based spatial statistics (TBSS) approach was utilized to compare 3 Tesla
diffusion tensor imaging (DTI) data from 12 ET patients and 10 age- and gender
matched healthy individuals. Clinical scales, tremor frequency and amplitude as
measured by accelerometry were correlated with DTI data. RESULTS: ET patients
demonstrated mean (MD) and radial diffusivity (RD) abnormalities in tracts
involved in primary and associative motor functions such as bilateral
corticospinal tracts, the superior longitudinal fascicles, and the corpus
callosum but also in nonmotor regions including the inferior fronto-occipital and
longitudinal fascicles, cingulum bundles, anterior thalamic radiations, and
uncinate fascicles. A combined tremor frequency and amplitude score correlated
with RD and MD in extensive WM areas, which partially overlapped the regions that
were associated with tremor frequency. No significant relationship was found
between DTI measures and clinical rating scales scores. CONCLUSIONS: The results
show that ET-related diffusion WM changes and their correlates with tremor
severity are preferentially located in the primary and associative motor areas.
In contrast, a relationship between WM was not detected with clinical rating
scales. Accelerometry parameters may, therefore, serve as a potentially useful
clinical measures that relate to WM deficits in ET.
PMID- 29964317
TI - Hazardous impacts of silver nanoparticles on mouse oocyte maturation and
fertilization and fetal development through induction of apoptotic processes.
AB - Silver nanoparticles (AgNPs) are antibacterial materials widely used in numerous
products and medical supplies. Previously, we showed that AgNPs trigger apoptotic
processes in mouse blastocysts, leading to a decrease in cell viability and
impairment of preimplantation and postimplantation embryonic development in vitro
and in vivo. In the present study, we further investigated the hazardous effects
of AgNPs on mouse oocyte maturation, in vitro fertilization (IVF), and subsequent
preimplantation and postimplantation development in vitro and in vivo. Data from
in vitro experiments revealed that AgNPs impair mouse oocyte maturation, decrease
IVF rates, and induce injury effects on subsequent embryonic development to a
significant extent. In an animal model, intravenous injection of AgNPs (5 mg/kg
body weight) led to a significant decrease in mouse oocyte maturation and IVF
concomitant with impairment of early embryonic development in vivo. Importantly,
pretreatment with N-acetylcysteine effectively prevented AgNP-triggered reactive
oxygen species (ROS) production and apoptosis, clearly suggesting a critical role
of ROS as an upstream initiator or key regulator of AgNP-induced hazardous
effects on oocyte maturation and sequent embryonic development. Furthermore,
preincubation of oocytes with Ac-DEVD-cho, a caspase-3-specific inhibitor,
effectively prevented hazardous effects, highlighting the potential involvement
of caspase-dependent apoptotic signaling cascades in AgNP-mediated events.
Expression levels of p53 and p21 of blastocysts were upregulated upon
preincubation of mouse oocytes with AgNPs. Our collective results imply that cell
apoptosis in mouse blastocysts derived from the AgNP-pretreated oocytes via
intracellular ROS generation, which is further mediated through p53-, p21-, and
caspase-3-dependent regulatory mechanisms.
PMID- 29964318
TI - Simultaneous determination of free and total choline and l-carnitine in infant
formula using hydrophilic interaction liquid chromatography with tandem mass
spectrometry.
AB - A quick, simple, and reliable method was developed for the simultaneous
determination of free and total choline and l-carnitine in infant formula
employing a novel hydrophilic interaction liquid chromatography with tandem mass
spectrometry method. Microwave-assisted hydrolysis was used to shorten the
hydrolysis time to only 15 min. A novel Click XIon zwitterionic stationary phase
was chosen because it gave better retention, perfect resolution, and sharper
symmetrical peaks compared to traditional columns. The matrix effect under
different experimental conditions was evaluated by using the matrix effect
factor, which employs stable isotopically labeled internal standards and is more
appropriate for evaluating the matrix effect related to endogenous analytes. The
accuracy and precision of the method were validated with certified reference
materials. The fortified recovery values for choline and l-carnitine were between
85.0 and 104% with relevant standard deviations <5.0%. The established method was
applied to the analysis of real infant formulas, demonstrating its applicability
and feasibility.
PMID- 29964320
TI - Alterations in cellular lipid metabolism produce neutral lipid accumulation
following exposure to the organochlorine compound trans-nonachlor in rat primary
hepatocytes.
AB - Recent epidemiological studies have revealed significant positive associations
between exposure to organochlorine (OC) pesticides and occurrence of the
metabolic syndrome and there are a growing number of animal-based studies to
support causality. However, the cellular mechanisms linking OC compound exposure
and metabolic dysfunction remain elusive. Therefore, the present study was
designed to determine if direct exposure to three highly implicated OC compounds
promoted hepatic steatosis, the hepatic ramification of the metabolic syndrome.
First, the steatotic effect of p,p'-dichlorodiphenyldichloroethylene (DDE),
oxychlordane, and trans-nonachlor was determined in freshly isolated rat primary
hepatocytes. Exposure to trans-nonachlor significantly increased neutral lipid
accumulation as opposed to DDE and oxychlordane. To determine possible mechanisms
governing increased fatty acid availability, the effects of trans-nonachlor
exposure on fatty acid uptake, de novo lipogenesis, triglyceride secretion, and
fatty acid oxidation were explored. Trans-nonachlor did not significantly alter
fatty acid uptake. However, insulin-stimulated de novo lipogenesis as well as
basal expression of fatty acid synthase, a major regulator of lipogenesis were
significantly increased following trans-nonachlor exposure. Interestingly, there
was a significant decrease in fatty acid oxidation following trans-nonachlor
exposure. This decrease in fatty acid oxidation was accompanied by a slight, but
significant increase in oleic acid-induced cellular triglyceride secretion.
Therefore, taken together, the present data indicate direct exposure to trans
nonachlor has a more potent pro-steatotic effect than exposure to DDE or
oxychlordane. This pro-steatotic effect of trans-nonachlor appears to be
predominately mediated via increased de novo lipogenesis and decreased fatty acid
oxidation.
PMID- 29964319
TI - Hepatoprotective effect of ginsenoside Rg1 from Panax ginseng on carbon
tetrachloride-induced acute liver injury by activating Nrf2 signaling pathway in
mice.
AB - Oxidative stress and inflammatory response are well known to be involved in the
pathogenesis of acute liver injury. This study was performed to examine the
hepatoprotective effect of ginsenoside Rg1 (Rg1) against CCl4 -induced acute
liver injury, and further to elucidate the involvement of Nrf2 signaling pathway
in vivo and in vitro. Mice were orally administered Rg1 (15, 30, and 60 mg/kg) or
sulforaphane (SFN) once daily for 1 week prior to 750 MUL/kg CCl4 injection. The
results showed that Rg1 markedly altered relative liver weights, promoted liver
repair, increased the serum level of TP and decreased the serum levels of ALT,
AST and ALP. Hepatic oxidative stress was inhibited by Rg1, as evidenced by the
decrease in MDA, and increases in GSH, SOD, and CAT in the liver. Further
research demonstrated that Rg1 suppressed liver inflammation response through
repressing the expression levels of inflammation-related genes including TNF
alpha, IL-1beta, IL-6, COX-2, and iNOS. In addition, Rg1 enhanced antioxidative
stress and liver detoxification abilities by up-regulating Nrf2 and its target
genes such as GCLC, GCLM, HO-1, NQO1, Besp, Mrp2, Mrp3, Mrp4, and down-regulating
Cyp2e1. However, the changes in Nrf2 target-genes, as well as ameliorative liver
histology induced by Rg1 were abrogated by Nrf2 antagonist all-transretinoic acid
in vivo and Nrf2 siRNA in vitro. Overall, the findings indicated that Rg1 might
be an effective approach for the prevention against acute liver injury by
activating Nrf2 signaling pathway.
PMID- 29964321
TI - Collared peccary (Pecari tajacu) are susceptible to porcine reproductive and
respiratory syndrome virus (PRRSV).
AB - Collared peccary (Pecari tajacu) and pigs (Sus scrofa) are two members of
superfamily Suoidea that coexist in the Americas and share some of the same viral
infections. Although porcine reproductive and respiratory syndrome virus (PRRSV)
is among the most impactful pathogens of swine on a worldwide basis, the
susceptibility of peccaries to PRRSV has not been investigated. In this study,
three peccaries were intramuscularly inoculated with a PRRSV-2 field virus. One
PRRSV-inoculated pig served as a positive control and two pigs and one peccary as
negative controls. Serum samples were collected at regular intervals over a 23
day observation period and tested by PRRSV rtRT-PCR and isotype-specific (IgM,
IgA, IgG) PRRSV ELISAs. The detection of viremia (DPI 3-23) and a PRRSV-specific
humoural immune response (>=DPI 10) supported the conclusion that collared
peccary are susceptible to PRRSV. The results raise questions regarding the
natural history of PRRSV in non-Sus members of superfamily Suoidea and, more
broadly, their role in the evolution and ecology of PRRSV.
PMID- 29964322
TI - Caregiver experience, health-related quality of life and life satisfaction among
informal caregivers to patients with amyotrophic lateral sclerosis: A cross
sectional study.
AB - AIMS AND OBJECTIVES: This study set out to describe caregiver experience, health
related quality of life and life satisfaction among informal caregivers to
patients with amyotrophic lateral sclerosis and to explore factors associated
with caregivers' health-related quality of life and life satisfaction.
BACKGROUND: Knowledge about factors related to caregivers' health-related quality
of life and life satisfaction is important for identification of those at risk
for ill health and for development of support and care. DESIGN: A cross-sectional
study. METHODS: Forty-nine informal caregivers and 49 patients were included.
Standardised and study-specific questionnaires were used for data collection on
caregiver experience (Caregiver Reaction Assessment), health-related quality of
life (EuroQol Visual Analogue Scale, SF-36), life satisfaction (Life Satisfaction
Checklist) and caregiver- and patient-related factors. Associations were explored
by regression analyses. RESULTS: Both positive and negative caregiver experience
were reported, and health-related quality of life and life satisfaction were
below national reference values. Positive experience was associated with better
and negative with worse mental health-related quality of life. Factors related to
informal caregivers (sex, age, living conditions) and patients (anxiety and/or
depression) were related to caregivers' health-related quality and life
satisfaction. CONCLUSION: The results indicate the need to consider the
individual caregiver's experience when planning services, care and support. It is
important to adopt person-centred care, not only for patients but also for their
informal caregivers, as factors related to both parties were associated with the
informal caregivers' health-related quality of life and life satisfaction.
RELEVANCE TO CLINICAL PRACTICE: Our study suggests that promoting positive
experience and providing services and support to reduce negative aspects of
caregiving might be important strategies for healthcare personnel to improve
informal caregivers' health.
PMID- 29964324
TI - Detection of carcinoembryonic antigen in peritoneal fluid of patients undergoing
laparoscopic distal gastrectomy with complete mesogastric excision.
AB - BACKGROUND: Surgery for gastric cancer may result in free intraperitoneal cancer
cells. This study aimed to determine whether laparoscopic gastrectomy with
complete mesogastric excision (D2 + CME) reduces the number of free
intraperitoneal cancer cells. METHODS: Patients with gastric cancer who had a
conventional D2 or D2 + CME laparoscopic distal gastrectomy between April 2015
and February 2017 were included in the study. Intraoperative peritoneal washings
were collected before and after tumour resection. Reverse transcriptase
quantitative real-time PCR for carcinoembryonic antigen (CEA) was used to assess
the presence of gastric cancer cells. RESULTS: Eighty-five patients underwent
conventional D2 lymphadenectomy and 76 had the D2 + CME procedure. Of 161
peritoneal fluid samples obtained before gastrectomy, 137 (D2, 72; D2 + CME, 65)
had low CEA expression indicative of no cancer cells. After gastrectomy, high CEA
expression was detected in 23 of the 72 samples (32 per cent) from patients in
the D2 group, and in ten of the 65 samples (15 per cent) from the D2 + CME group.
In the overall cohort, mean CEA expression level after gastrectomy was lower in
the D2 + CME group than in the D2 group (P = 0.0038). In patients with low CEA
expression before gastrectomy, disease-free survival in the D2 + CME group was
better than that in the D2 group (P = 0.033). CONCLUSION: Laparoscopic distal
gastrectomy with complete mesogastric excision reduces the number of free
intraperitoneal cancer cells and is associated with a better disease-free
survival than conventional D2 gastrectomy.
PMID- 29964325
TI - Response to "The role of procalcitonin in the diagnosis and management of
infections in the field of obstetrics and gynecology".
PMID- 29964323
TI - Discovery of novel plasma biomarkers for future incident venous thromboembolism
by untargeted synchronous precursor selection mass spectrometry proteomics.
AB - : Essentials Discovery of predictive biomarkers of venous thromboembolism (VTE)
may aid risk stratification. A case-control study where plasma was sampled before
the occurrence of VTE was established. We generated untargeted plasma proteomic
profiles of 200 individuals by use of mass spectrometry. Assessment of the
biomarker potential of 501 proteins yielded 46 biomarker candidates. ABSTRACT:
Background Prophylactic anticoagulant treatment may substantially reduce the
incidence of venous thromboembolism (VTE) but entails considerable risk of severe
bleeding. Identification of individuals at high risk of VTE through the use of
predictive biomarkers is desirable in order to achieve a favorable benefit-to
harm ratio. Objective We aimed to identify predictive protein biomarker
candidates of VTE. Methods We performed a case-control study of 200 individuals
that participated in the Tromso Study, a population-based cohort, where blood
samples were collected before the VTE events occurred. Untargeted tandem mass tag
synchronous precursor selection-mass spectrometry (TMT-SPS-MS3)-based proteomic
profiling was used to study the plasma proteomes of each individual. Results Of
the 501 proteins detected in a sufficient number of samples to allow multivariate
analysis, 46 proteins were associated with VTE case-control status with P-values
below the 0.05 significance threshold. The strongest predictive biomarker
candidates, assessed by statistical significance, were transthyretin, vitamin K
dependent protein Z and protein/nucleic acid deglycase DJ-1. Conclusions Our
untargeted approach of plasma proteome profiling revealed novel predictive
biomarker candidates of VTE and confirmed previously reported candidates, thereby
providing conceptual support for the validity of the study. A larger nested case
control study will be conducted to validate our findings.
PMID- 29964326
TI - A score-based method for quality control of fetal hard palate assessment during
routine second-trimester ultrasound examination.
AB - INTRODUCTION: When an orofacial cleft lip is discovered, precise characterization
of this malformation is necessary, especially the extension of this cleft to the
secondary palate. We aimed to develop and evaluate the
feasibility/reproducibility of a score-based quality control for the
visualization of the fetal hard palate during the second-trimester scan. MATERIAL
AND METHODS: All ultrasound images of fetal hard palate assessed routinely during
second-trimester scan were retrospectively retrieved for a 6-month period. One
hundred of these images were randomly selected and analyzed by two blinded
reviewers, according to a scoring system (0-6 points). Criteria retained in the
score were complete palate bone horizontal plate, presence of two pterygoid
processes, visible alveolar ridge, and horizontal axis of insonation. A score >=4
defined images of good quality. Inter- and intra-reviewer reproducibility was
assessed. RESULTS: Inter-reviewer reproducibility was excellent with significant
correlation (Pearson coefficient 0.953; P < .0001), global adjusted kappa
coefficient (0.86, 95% CI 0.79-0.94) and individual criteria adjusted kappa
coefficient always > 0.8. Rates of images of good quality (score >= 4) were 75%
77%, also with excellent agreement (kappa coefficient 0.89, 95% CI 0.79-0.99).
Intra-reviewer reproducibility retrieved the same results (excellent agreement)
except for the axis of insonation (satisfactory agreement). CONCLUSIONS: This
simple image scoring system for the fetal palate is easy, has excellent inter-
and intra-reviewer reproducibility and could also help sonographers to correctly
identify the palate structure.
PMID- 29964327
TI - Notch pathway inhibition using DAPT, a gamma-secretase inhibitor (GSI), enhances
the antitumor effect of cisplatin in resistant osteosarcoma.
AB - Overcoming platinum drug resistance represents a major clinical challenge in
osteosarcoma (OS) treatment. The high rates and patterns of therapeutic failure
seen in patients are consistent with a steady accumulation of drug-resistant
cancer stem cells (CSCs). Notch signaling is implicated in regulating CSCs and
tumor resistance to platinum. Thus, we attempt to investigate whether inhibiting
of Notch pathway could sensitize cisplatin (CDDP) to CDDP-resistant OS cells and
the underlying molecular mechanisms. OS cell lines resistant to CDDP were treated
with DAPT, CDDP or combination, we present evidences that DAPT enhances the
cytotoxic effect of CDDP in resistant OS by inhibiting proliferation, resulting
in G0/G1 cell-cycle arrest, inducing apoptosis, and reducing motility. In
addition, DAPT targeting depletes OS stem cells (OSCs), thus increasing tumor
sensitivity to platinum, which indicating that a dual combination targeting both
OSCs and the bulk of tumor cells are needed for tumor eradication. We also found
that the combination of CDDP and DAPT exhibit additive suppression on
phosphorylated AKT and ERK, contributing to the anti-cancer effects. In animal
model, this combination therapy inhibits the growth and metastasis of CDDP
resistant tumor xenografts in nude mice to a greater extent than treatment with
either reagent alone. Based on these results, we conclude that CDDP plus DAPT was
able to sensitize CDDP-resistant human OS cells to CDDP by downregulation of
Notch signaling. CDDP and DAPT combination treatment may be effective and
promising for advanced OS.
PMID- 29964328
TI - TCR-pMHC interactions: Two peptide repertoires-one signal.
AB - The peptide (P) ligand seen by the TCR is presented by an MHC-encoded restricting
element (R). Peptide is viewed from two perspectives, that of the TCR and that of
R. The TCR looks at P using an anti-P site that is somatically generated and
selected, whereas R looks at P using a binding site that is germline generated
and selected. The two segments of P, the one viewed by the TCR, the other viewed
by R divide P into two repertoires, Ptcr and Pr that are recognized independently
but function cooperatively. The consequences of this for an understanding of TCR
specificity and signalling as well as the role of differential processing are
analysed. It is ironic that from the point of view of the immunologist, the TCR
is highly polyreactive recognizing over a million peptides, whereas from the
point of view of the immune system, the TCR is highly specific recognizing
essentially only one epitope.
PMID- 29964330
TI - Stabilization by Benzannulation: Butterfly Azaacenes.
AB - Soluble butterfly-shaped tetraazapentacenes and tetraazaheptacenes were prepared
by condensation or Stille coupling with a stannafluorene. The stability of the
benzo-winged tetraazaheptacene is dramatically increased through the fourfold
benzannulation, yet its acene character is retained to a significant extent.
PMID- 29964329
TI - The combination of ribose and adenine promotes adenosine release and attenuates
the intensity and frequency of epileptiform activity in hippocampal slices:
Evidence for the rapid depletion of cellular ATP during electrographic seizures.
AB - In addition to being the universal cellular energy source, ATP is the primary
reservoir for the neuromodulator adenosine. Consequently, adenosine is produced
during ATP-depleting conditions, such as epileptic seizures, during which
adenosine acts as an anticonvulsant to terminate seizure activity and raise the
threshold for subsequent seizures. These actions protect neurones from excessive
ionic fluxes and hence preserve the remaining cellular content of ATP. We have
investigated the consequences of manipulation of intracellular ATP levels on
adenosine release and epileptiform activity in hippocampal slices by pre
incubating slices (3 h) with creatine (1 mM) and the combination of ribose (1 mM)
and adenine (50 MUM; RibAde). Creatine buffers and protects the concentration of
cellular ATP, whereas RibAde restores the reduced cellular ATP in brain slices to
near physiological levels. Using electrophysiological recordings and
microelectrode biosensors for adenosine, we find that, while having no effect on
basal synaptic transmission or paired-pulse facilitation, pre-incubation with
creatine reduced adenosine release during Mg2+- free/4-aminopyridine-induced
electrographic seizure activity, whereas RibAde increased adenosine release. This
increased release of adenosine was associated with an attenuation of both the
intensity and frequency of seizure activity. Given the depletion of ATP after
injury to the brain, the propensity for seizures after trauma and the risk of
epileptogenesis, therapeutic strategies elevating the cellular reservoir of
adenosine may have value in the traumatized brain. Ribose and adenine are both in
use in man and thus their combination merits consideration as a potential
therapeutic for the acutely injured central nervous system.
PMID- 29964331
TI - Inhibition of euchromatin histone-lysine N-methyltransferase 2 sensitizes breast
cancer cells to tumor necrosis factor-related apoptosis-inducing ligand through
reactive oxygen species-mediated activating transcription factor 4-C/EBP
homologous protein-death receptor 5 pathway activation.
AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been
characterized as an anti-cancer therapeutic agent with prominent cancer cell
selectivity over normal cells. However, breast cancer cells are generally
resistant to TRAIL, thus limiting its therapeutic potential. In this study, we
found that BIX-01294, a selective inhibitor of euchromatin histone
methyltransferase 2/G9a, is a strong TRAIL sensitizer in breast cancer cells. The
combination of BIX-01294 and TRAIL decreased cell viability and led to an
increase in the annexin V/propidium iodide-positive cell population, DNA
fragmentation, and caspase activation. BIX-01294 markedly increased death
receptor 5 (DR5) expression, while silencing of DR5 using small interfering RNAs
abolished the TRAIL-sensitizing effect of BIX-01294. Specifically, BIX-01294
induced C/EBP homologous protein (CHOP)-mediated DR5 gene transcriptional
activation and DR5 promoter activation was induced by upregulation of the protein
kinase R-like endoplasmic reticulum kinase-mediated activating transcription
factor 4 (ATF4). Moreover, inhibition of reactive oxygen species by N-acetyl-L
cysteine efficiently blocked BIX-01294-induced DR5 upregulation by inhibiting
ATF4/CHOP expression, leading to diminished sensitization to TRAIL. These
findings suggest that BIX-01294 sensitizes breast cancer cells to TRAIL by
upregulating ATF4/CHOP-dependent DR5 expression with a reactive oxygen species
dependent manner. Furthermore, combination treatment with BIX-01294 and TRAIL
suppressed tumor growth and induced apoptosis in vivo. In conclusion, we found
that epigenetic regulation can contribute to the development of resistance to
cancer therapeutics such as TRAIL, and further studies of unfolded protein
responses and the associated epigenetic regulatory mechanisms may lead to the
discovery of new molecular targets for effective cancer therapy.
PMID- 29964332
TI - Waist-to-hip ratio is a better predictor than body mass index for morbidity in
abdominally based breast reconstruction.
AB - BACKGROUND: Body mass index is a universally recognized measure of obesity.
However, it does not take body fat distribution (BFD) into account, which has
been established as a significant risk factor in both medicine and surgery. The
objective of this study was to compare previously developed anthropometric
measures of BFD with body mass index in predicting morbidity with abdominally
based microsurgical breast reconstruction. METHODS: A review of patients who
underwent abdominally based breast reconstruction was performed. Multivariate
logistic regression was performed to determine the relationship between
complications (recipient, donor, total) with body mass index, waist
circumference, waist-to-hip ratio, waist-to-height ratio, conicity index, and
abdominal volume index. RESULTS: A total of 325 patients who underwent 442 flaps
were analyzed. Waist circumference (OR, 1.16; 95% CI 1.07-1.76), waist-to-hip
ratio (OR, 1.94; 95% CI 1.25-3.35), and waist-to-height ratio (OR, 1.19; 95% CI
1.01-1.70) were significant risk factors for recipient site complications. Body
mass index (OR, 1.14; 95% CI 1.01-1.56), and waist-to-hip ratio (OR, 2.01; 95% CI
1.30-3.95) were significant risk factors for donor site complications. Waist-to
hip ratio (OR, 1.87; 95% CI 1.22-4.00) was the only measure found to be a
significant risk factor for experiencing any complication. A waist-to-hip ratio
>0.84 was associated with increased risk. CONCLUSIONS: Waist-to-hip ratio is a
significant risk factor for recipient and donor site morbidity in abdominally
based breast reconstruction. It is a readily calculable and clinically
significant measure distinct from body mass index that should be considered for
use in clinical care and research.
PMID- 29964333
TI - Using a novel self-help inflatable balloon to prevent esophageal stricture after
complete circular endoscopic submucosal dissection.
PMID- 29964334
TI - Patient support during treatment for active tuberculosis and for latent
tuberculosis infection: Policies and practices in European low-incidence
countries.
AB - AIM: To provide an overview of the policies and practices of patient support
during treatment for active tuberculosis and for latent tuberculosis infection in
European countries with a low incidence of tuberculosis and to identify potential
best practices. BACKGROUND: Policies, practices and its' evaluations from similar
settings may aid in the development of evidence-based patient support guidelines.
DESIGN: Descriptive study. METHODS: In June 2016, a survey was conducted among
the 24 European low tuberculosis incidence countries (<20 patients per 100,000
population). RESULTS: Nineteen of the 24 countries approached responded. Most
countries (18/19) gave some form of tuberculosis patient support including
various treatment supervision options and treatment adherence interventions such
as health education, psycho-emotional and socio-economic support. Patient support
for persons on treatment for latent tuberculosis infection was less widely (9/19)
implemented. Patient support guidelines were available in 13 countries, but none
of the interventions included had been quantitatively evaluated for their effects
on treatment adherence. Potential best practices included appointing a
tuberculosis coordinator in charge of organizing patient support; putting a
treatment plan meeting with patients, providers and stakeholders in place;
supplying direct enablers for marginalized patients; organizing cultural
sensitive community support; and dispensing pill cases. A lack of resources
impeded the provision of patient support, especially for home-based treatment
supervision. CONCLUSION: We summarized policies and practices of tuberculosis and
latent tuberculosis infection patient support in low tuberculosis incidence
European countries. Given the lack of quantitative evaluations, more research is
needed to verify the effectiveness of identified potential best practices.
PMID- 29964335
TI - Indigo naturalis-induced colitis.
PMID- 29964336
TI - A Nanosized Phenylene-Ethynylene-Butadiynylene [2]Catenane.
AB - In a convergent, template-directed synthesis, an efficient route to a phenylene
ethynylene-butadiynylene based [2]catenane is described. The key step is
performed by the aminolysis of the corresponding precatenane, which is obtained
by a sequence of metal-catalyzed cross-coupling and desilylation reactions. The
cyclization reaction leads besides the [2]precatenane to a variety of larger
precatenanes and offers an attractive approach to mechanically interlocked
structures of different size.
PMID- 29964337
TI - MALAT1 promotes the colorectal cancer malignancy by increasing DCP1A expression
and miR203 downregulation.
AB - The long non-coding RNA MALAT1 has been proved to promote the cell proliferation,
drug resistance, invasion, and metastasis of colorectal cancer (CRC) in vitro and
in vivo by regulating the expression of various oncogenes and their protein
products. Our previous work discovered that the expression of the mRNA-decapping
enzymes 1a (DCP1A) is upregulated in CRCs. However, the relationships between
MALAT1 and DCP1A in the development of CRC and the underlying mechanisms are
still unclear. In this study, we investigated the molecular mechanisms by which
MALAT1 and DCP1A may be linked to contribute to the malignancies of CRCs. We
found that DCP1A is a direct target molecule of MALAT1. Moreover, by screening
the downstream genes of MALAT1, we noticed that microRNA 203(miR203), an oncogene
suppressor in numerous cancers, is inversely correlated to both MALAT1 and DCP1A
expressions. Following MALAT1 knockdown, we observed overexpression of miR203
accompanied with DCP1A downregulation to a level that reversed the promoted cell
proliferation, invasion, and migration in vitro and in vivo, which could be
restored by miR203 knockdown or DCP1A overexpression. These results proposed a
new molecular mechanism of MALAT-miR203-DCP1A axis which is involved with the
development and contributes to the malignancy of colorectal cancers.
PMID- 29964338
TI - Elevated hydrostatic pressure promotes ameloblastoma cell invasion through
upregulation of MMP-2 and MMP-9 expression via Wnt/beta-catenin signalling.
AB - BACKGROUND: The process of marsupialization involves the release of intracystic
pressure and the fluid contained within. Marsupialization of cystic ameloblastoma
is controversial; therefore, we investigated how hydrostatic pressure influences
biological behaviours of ameloblastoma cells and its underlying mechanisms.
MATERIALS AND METHODS: An ameloblastoma epithelial cell line, hTERT+ -AM, was
exposed to different hydrostatic pressures with or without Dickkopf-related
protein 1 (also known as DKK), a canonical Wnt signalling pathway inhibitor. A
CCK-8 assay, a monolayer wound assay, and a Transwell assay were used to
determine cell proliferation, migration and invasion, respectively. qRT-PCR and
Western blot were used to detect expression of MMP-2, MMP-9, RANKL and other
downstream targets of Wnt signalling. RESULTS: Elevated hydrostatic pressure
promoted migration and invasion of ameloblastoma cells, but inhibited
proliferation. Expression of MMP-2, MMP-9, LEF-1, cyclin D1, c-Jun and c-Myc was
significantly upregulated under elevated hydrostatic pressure, and these effects
could be abolished by DKK1. Expression of RANKL, which is thought to be a
downstream target of Wnt signalling, did not significantly change under elevated
hydrostatic pressure. CONCLUSIONS: This study indicates that elevated hydrostatic
pressure promotes the migration and invasion of ameloblastoma cells by activating
the Wnt/beta-catenin pathway, thereby increasing expression of MMP-2, MMP-9 and
other Wnt signalling downstream targets. This suggests that marsupialization may
reduce invasiveness and reverse the bone resorption process by lowering
intracystic hydrostatic pressure in cystic ameloblastoma.
PMID- 29964339
TI - Argon plasma coagulation treatment of biliary adenomas in a patient with familial
adenomatous polyposis.
PMID- 29964340
TI - Protein interactions of FAM134B with EB1 and APC/beta-catenin in vitro in colon
carcinoma.
AB - FAM134B is an autophagy regulator of endoplasmic reticulum and acts as a cancer
suppressor in colon cancer. However, the molecular signaling pathways by which
FAM134B interacts within colon carcinogenesis is still unknown. Herein, this
study aims to determine the interacting partners of FAM134B for the first time in
colon cancer and to explore the precise location of FAM134B in cancer signalling
pathways. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)
followed by anti-FAM134B co-immune precipitation of FAM134B interacting complex
was used to identify the potential interactors of FAM134B in colon cancer cells.
Western blot and confocal microscopic analysis were used to validate the physical
interactions of FAM134B with the interactors. Lentiviral shRNA mediated silencing
of FAM134B was used to examine the modulation of FAM134B interactors in cells. We
have identified 29 novel binding partners, including CAP1, RPS28, FTH1, KDELR2,
MAP4, EB1, PSMD6, PPIB/CYPB etc. Subsequent immunoassays confirmed the direct
physical interactions of FAM134B with CAP1, EB1, CYPB, and KDELR2 in colon cancer
cells. Exogenous suppression of FAM134B has led to significant upregulation of
EB1 as well as reduction of KDELR2 expression. It was noted that overexpression
of EB1 promotes WNT/beta-catenin signaling pathways via inactivating tumor
suppressor APC followed by activating beta-catenin in colorectal carcinogenesis.
This study has first time reported the gene signaling networks with which FAM134B
interacts and noted that FAM134B is involved in the regulation of WNT/beta
catenin pathway by EB1-mediated modulating of APC in colon cancer cells.
PMID- 29964341
TI - Erratum.
PMID- 29964342
TI - Commentary on: Chen HI, deJong J. Increased lung weights in drug-related
fatalities. J Forensic Sci 2017;62(6):1632-4.
PMID- 29964343
TI - Classification Improvements in Automated Gunshot Residue (GSR) Scans.
AB - Classification of particles as gunshot residues (GSRs) is conducted using a
semiautomatic approach in which the system first classifies particles based on an
automatic elemental analysis, and then, examiners manually analyze particles
having compositions which are characteristic of or consistent with GSRs.
Analyzing all the particles in the second stage is time consuming with many
particles classified by the initial automated system as being potentially GSRs
excluded as such by the forensic examiner. In this paper, a new algorithm is
developed to improve the initial classification step. The algorithm is based on a
binary tree that was trained on almost 16,000 particles from 43 stubs used to
sample hands of suspects. The classification algorithm was tested on 5,900
particles from 23 independent stubs and performed very well in terms of false
positive and false negative rates. A routine use of the new algorithm can reduce
significantly the analysis time of GSRs.
PMID- 29964344
TI - Usability of a wearable fall detection prototype from the perspective of older
people-A real field testing approach.
AB - AIMS AND OBJECTIVES: Community-dwelling older people were involved in the testing
of a fall detection device to improve its utilisation and acceptance in everyday
life. BACKGROUND: The usability of alerting devices remains unsatisfactory, as
they are scarcely utilised by older people, despite wide recognition of the
importance of rapid assistance after a fall. Moreover, the time a person remains
on the floor negatively impacts the severity of fall consequences. However, it is
unclear how to increase alerting device utilisation in everyday life. Therefore,
older people were involved in this research to consider their perspective during
prototype development. DESIGN: A qualitative focus group study was conducted,
following a real field testing approach, underpinned by the theoretical framework
"Medical Device Technology Development Process." METHODS: Fifteen community
dwelling older people tested the prototype in daily living over a period of nine
days. Different means of involvement were exploited such as "user seminars" or
"discussion with users." On day 9, data were collected using focus groups and
analysed with qualitative content analysis. RESULTS: The participants'
perspectives yielded positive aspects of the prototype along with aspects
requiring improvement. They indicated that technical requirements are essential.
They also revealed that a minimal change in daily routines, support for physical
activity and independent living and the inclusion of trusted contact persons
could lead to wider use of the alerting device. CONCLUSIONS: Involving users is
crucial in gaining a deeper understanding of aspects influencing utilisation of
an alerting device. The study revealed that usability is influenced both by
technical requirements as well as habits and personal preferences. This finding
is vital, as habits and personal preferences can only be identified through the
involvement of target users. RELEVANCE TO CLINICAL PRACTICE: The study provides
key insights for health practitioners interested in promoting the use of an
alerting device in community-dwelling older people.
PMID- 29964345
TI - White matter microstructure in anorexia nervosa.
AB - The neurobiological underpinnings of anorexia nervosa (AN) are unclear. White
matter deficits have been described in the illness, but findings are inconsistent
between studies. The aim of this study was to investigate differences in white
matter microstructure in AN using diffusion-weighted imaging (DWI). It was
hypothesised that people with AN, relative to a healthy control (HC) group, would
show decreased functional anisotropy (FA) and increased mean diffusivity (MD) in
the fornix and superior longitudinal fasciculus, consistent with previous
literature. Analyses were conducted on 23 females with AN and 26 age- and gender
matched HCs using tract-based spatial statistics (TBSS). The results revealed
widespread FA decreases and MD increases in the AN group. Our hypothesis was
largely supported, although FA differences were not specifically found in the
fornix. The findings suggest extensive differences in white matter structure in
AN, which may contribute to AN pathophysiology.
PMID- 29964346
TI - Selective binding of potassium and calcium ions to novel cyclic proanthocyanidins
in wine by HPLC-HRMS.
AB - RATIONALE: Cyclic B-type (referred also as crown) proanthocyanidins were recently
identified in wines. An HPLC-HRMS/MS method was applied to study the binding of
cyclic and non-cyclic PAC to potassium and calcium ions, which affect the chemico
physical stability of wines. Different binding affinities suggest that cyclic and
non-cyclic analogues, despite the equal number of monomer units, influence the
colloidal stability of wine and are related to the grape variety or winemaking
conditions. METHODS: Nineteen red and white wines were analysed by HPLC high
resolution tandem mass spectrometry with positive electrospray ionization to
investigate the distribution of novel cyclic proanthocyanidins and their calcium,
potassium and sodium adducts. Principal Component Analysis was used to study the
distribution of the wines and the relationships among proanthocyanidins with and
without cation complexes. RESULTS: A dependence on specific isomers (and
conformations) was found for the non-cyclic procyanidin (PC) trimer whereas the
cyclic tetrameric PAC were shown to bind better to potassium than their non
cyclic analogues. The binding to these metals appeared to be influenced not only
be the number of monomer units but also by the conformation assumed by the
molecules. Statistical analysis evidenced that the adducts distribution in
different wines is less influenced by the grape variety used for winemaking than
their associated [M+H]+ species studied earlier. CONCLUSIONS: Wines from 19 grape
varieties were investigated in order to identify potassium and calcium complexes
of non- and cyclic B-type proanthocyanidins that were recently discovered. The
results showed a dependence of the distribution of metal complexes according to
the cyclic or non cyclic geometry of proanthocyanidins. The multivariate analysis
of the mass spectrometric results showed a relationship with the grape variety,
however not so straightforward as evidenced for the non-complexed species.
PMID- 29964347
TI - Hydrophobic-Force-Driven Removal of Organic Compounds from Water by Reduced
Graphene Oxides Generated in Agarose Hydrogels.
AB - Hydrophobic reduced graphene oxides (rGOs) were generated in agarose hydrogel
beads (AgarBs) by NaBH4 reduction of graphene oxides (GOs) initially loaded in
the AgarBs. The resulting rGO-loaded AgarBs were able to effectively adsorb
organic compounds in water as a result of the attractive hydrophobic force
between the rGOs in the AgarBs and the organic compounds dissolved in aqueous
media. The adsorption capacity of the rGOs was fairly high even toward reasonably
water-soluble organic compounds such as rhodamine B (321.7 mg g-1 ) and aspirin
(196.4 mg g-1 ). Yet they exhibited salinity-enhanced adsorption capacity and
preferential adsorption of organic compounds with lower solubility in water. Such
peculiar adsorption behavior highlights the exciting possibility for adopting an
adsorption strategy, driven by hydrophobic forces, in practical wastewater
treatment processes.
PMID- 29964348
TI - Neural correlates of gender congruence in audiovisual commercials for gender
targeted products: An fMRI study.
AB - This article explores neural and self-report responses to gender congruence in
product-voice combinations in commercials. An fMRI study was carried out in which
participants (n = 30) were presented with gender-targeted pictures of
characteristic male or female products accompanied by either gender congruent or
incongruent voices. The findings show that attitudes are more positive toward
commercials with gender congruent than with gender incongruent product-voice
combinations. fMRI analyses revealed that primary visual brain areas, namely
calcarine and cuneus, responded stronger to congruent than incongruent
combinations suggesting that participants enhanced their endogenous attention
toward congruent commercials. Incongruent combinations, by contrast, elicited
stronger activation in areas related to the perception of conflicts in
information processing and error monitoring, such as the supramarginal, inferior
parietal gyri and superior, and middle temporal gyri. Interestingly, increased
activation in the posterior cingulate cortex (an area related to value encoding)
predicted more positive attitudes toward congruent commercials. Together, these
results advance our understanding of the neural correlates of processing
congruent and incongruent audiovisual stimuli. These findings may advice
advertising professionals in designing successful campaigns of everyday products,
namely by making use of congruent instead of incongruent product-voice
combinations.
PMID- 29964349
TI - Predictors of hospital-acquired pressure ulcers among older adult inpatients.
AB - AIM AND OBJECTIVES: To provide basic information on the preventive care for
pressure ulcer (PU) by analysing PU-related characteristics and identifying PU
predictors. BACKGROUND: The incidence of PUs in hospitals is increasing, and
continuous PU management is required. The occurrence of PU was an important
standard for hospital certification. There is a need to identify predictors of
PUs for proper management of PUs. DESIGN: This is a descriptive study that
analyses the electronic medical records of a university hospital. METHODS: Of all
older adult inpatients aged over 65 years admitted to the hospital (from January
1, 2011-December 31, 2015), 34,287 were included in this study. To identify the
PU predictors, a logistic regression analysis was performed using IBM SPSS
Statistics 24. RESULTS: Predictors influencing PU were gender (OR = 1.36, 95% CI
= 1.03-1.05), age, (OR = 1.04, 95% CI = 1.03-1.05), admission method (OR = 0.39,
95% CI = 0.32-0.46), consciousness status (OR = 3.77, 95% CI = 1.83-7.77) and
Braden Scale score (OR = 0.07, 95% CI = 0.69-0.72). Among the predictors,
consciousness is the most important variable. Patients who are drowsy were 3.77
times more likely to develop PU than those who are alert. CONCLUSIONS: To prevent
and manage PU, the level of consciousness of older adult patients who are
hospitalised should be assessed, and appropriate interventions should be
provided. RELEVANCE TO CLINICAL PRACTICE: Pressure ulcer-specific interventions
should be provided systematically by healthcare providers to those with altered
consciousness beginning at hospital admission.
PMID- 29964350
TI - Viruses as indicators of contemporary host dispersal and phylogeography: an
example of feline immunodeficiency virus (FIVP le ) in free-ranging African lion
(Panthera leo).
AB - Measuring contemporary dispersal in highly mobile terrestrial species is
challenging, especially when species are characterized by low levels of
population differentiation. Directly transmitted viruses can be used as a
surrogate for traditional methods of tracking host movement. Feline
immunodeficiency virus (FIV) is a species-specific lentivirus, which has an
exceptionally high mutation rate and circulates naturally in wild felids. Using
samples derived from 35 lion (Panthera leo) prides, we tested the prediction that
FIV in lions (FIVP le ) can be used to track the dispersal of individuals between
prides. As FIVP le subtypes are geographically structured throughout Africa, we
predicted that this marker could be used to detect phylogeographic structure of
lions at smaller spatial scales. Phylogenetic analyses of FIVP le pol-RT
sequences showed that core pride members (females and subadults) shared
evolutionary close viral lineages which differed from neighbouring core prides,
whereas sequences from sexually mature males associated with the same pride were
always the most divergent. In six instances, natal pride associations of
divergent male lions could be inferred, on the assumption that FIVP le infections
are acquired during early life stages. Congruence between the genetic pattern of
FIV and pride structure suggests that vertical transmission plays an important
role in lion FIV dynamics. At a fine spatial scale, significant viral geographic
structuring was also detected between lions occurring north of the Olifants River
within the Kruger National Park (KNP) and those occupying the southern and
central regions. This pattern was further supported by phylogenetic analyses and
the confinement of FIVP le subtype E to the northern region of KNP. The study
provides new insights into the use of retroviral sequences to predict host
dispersal and fine-scale contemporary geographic structure in a social felid
species.
PMID- 29964351
TI - Biosurfactant-facilitated leaching of metals from spent hydrodesulphurization
catalyst.
AB - AIMS: To investigate the capabilities of different types of biosurfactants
(rhamnolipids, lipopeptides, sophorolipids) to remove metals and carbon from the
hazardous spent hydrodesulphurization (HDS) catalyst generated by petroleum
refineries. METHODS AND RESULTS: Biosurfactants were prepared and used to treat
spent HDS catalyst. Metal and carbon contents were analysed and compared with
those from no-biosurfactant control treatments. All biosurfactant treatments
increased carbon loss percentage from the spent HDS catalyst. The lipopeptide
treatment LI, containing 17.34 mg ml-1 of crude biosurfactants, caused the
highest carbon loss percentage (44.5%). Rhamnolipids were, in general, better
than sophorolipids and lipopeptides as metal-removing agents. The metal content
decreased as the concentration of rhamnolipids decreased. The R5 treatment, which
contained 0.4 mg l-1 of crude rhamnolipids, caused the highest reduction in metal
content. Molybdenum, nickle and vanadium contents were reduced by 90, 30 and 70%
respectively. CONCLUSIONS: Biosurfactants might have potential application for
metals and coke removal from spent HDS catalysts. The bioleaching capability
depends on the type and concentration of the biosurfactant. SIGNIFICANCE AND
IMPACT OF THE STUDY: This study, after further in-depth investigations, might
lead to the development of an eco-friendly and economic technology to treat or
even regenerate the environmentally hazardous spent HDS catalysts, which are
generated in huge amounts by the petroleum refineries.
PMID- 29964352
TI - The mental health plight of unaccompanied asylum-seeking children in detention.
PMID- 29964353
TI - Major histocompatibility complex variation and blood parasites in resident and
migratory populations of the common yellowthroat.
AB - Genes of the major histocompatibility complex (MHC) are a critical part of the
adaptive immune response, and the most polymorphic genes in the vertebrate
genome, especially in passerine birds. This diversity is thought to be influenced
by exposure to pathogens which can vary in relation to numerous factors.
Migratory behaviour may be a particularly important trait to consider because
migratory birds are exposed to a greater number of different pathogens and
parasites at both breeding (i.e. temperate) and overwintering (i.e. tropical and
subtropical) areas, as well as at stopover sites during migration. Thus, migrants
are predicted to have greater MHC diversity than residents. We compared MHC
variation, at both class I and II, and levels of haemosporidian infection between
one resident and two migratory populations of the common yellowthroat (Geothlypis
trichas). We found that residents were less likely to be infected with
haemosporidian parasites and had lower MHC diversity at class I; however,
variation at MHC class II was greater in residents than migrants, contrary to our
prediction. These patterns were not likely to be caused by differences in
population demography as genomewide heterozygosity (based on 9225 single
nucleotide polymorphisms) was high in all three populations and not correlated
with MHC variation. Our different results for MHC class I and II suggest that
studies of immune gene variation in relation to life history need to consider
that there could be different selection pressures arising from intracellular
(class I) and extracellular (class II) pathogens in different populations.
PMID- 29964354
TI - Abstracts of the 68th annual meeting in University of Nottingham.
AB - Placental hypervascularization observed in gestational diabetes mellitus (GDM)
may be related to functional availability of vascular endothelial growth factor
(VEGF) and its receptors. We aimed to test whether changes in phosphorylation of
tyrosine 951 or tyrosine 1175 (pY951 or pY1175) of the vascular endothelial
growth factor receptor 2 (VEGFR2) are associated with the proangiogenic state
observed in placentas from GDM This article is protected by copyright. All rights
reserved.
PMID- 29964355
TI - Knockout of human arylamine N-acetyltransferase 1 (NAT1) in MDA-MB-231 breast
cancer cells leads to increased reserve capacity, maximum mitochondrial capacity,
and glycolytic reserve capacity.
AB - Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic
metabolizing enzyme found in almost all tissues. NAT1 can also hydrolyze acetyl
coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. Expression of
NAT1 varies between individuals and is elevated in several cancers including
estrogen receptor positive (ER+) breast cancers. To date, however, the exact
mechanism by which NAT1 expression affects mitochondrial bioenergetics in breast
cancer cells has not been described. To further evaluate the role of NAT1 in
energy metabolism MDA-MB-231 breast cancer cells with parental, increased, and
knockout levels of NAT1 activity were compared for bioenergetics profile. Basal
oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were
measured followed by programmed sequential injection of Oligomycin (ATP synthase
inhibitor), FCCP (ETC uncoupler), Antimycin A (Complex III inhibitor), and
Rotenone (Complex I inhibitor) to evaluate mitochondrial bioenergetics. Compared
to the cell lines with parental NAT1 activity, NAT1 knockout MDA-MB-231 cell
lines exhibited significant differences in bioenergetics profile, while those
with increased NAT1 did not. Significant increases in reserve capacity, maximum
mitochondrial capacity, and glycolytic reserve capacity were observed in NAT1
knockout MDA-MB-231 cell lines compared to those with parental and increased NAT1
activity. These data indicate that NAT1 knockout in MDA-MB-231 breast cancer
cells may enhance adaptation to stress by increasing plasticity in response to
energy demand.
PMID- 29964357
TI - Forensic analysis of water-based lubricants using liquid extraction surface
analysis high-resolution tandem mass spectrometry.
AB - RATIONALE: Analysis of water-based personal lubricants can provide pivotal
information to law enforcement regarding sexual assault allegations, particularly
in the absence of biological evidence. Traditional methodology for the extraction
and analysis of water-based lubricants is cumbersome, time-consuming, and is
often not sufficiently selective or sensitive to fully characterise the wide
range of chemical components present within complex formulations. METHODS: Liquid
extraction surface analysis (LESA) was deployed in combination with high
resolution mass spectrometry (HRMS) and tandem mass spectrometry (MS/MS) to
screen a range of water-based lubricants directly from contaminated cotton
fabric. Rehydration of the fabric was the only sample preparation required.
RESULTS: Analysis of ten different water-based lubricants by nano-electrospray
ionisation mass spectrometry in negative ion mode enabled discrimination based on
the presence or absence of nine compounds, which were identified by comparison of
their MS/MS spectra with those of available standards. Lubricants were
successfully detected by LESA from stained fabric surfaces; even following
extended periods of time between deposition and sampling. CONCLUSIONS: A library
encompassing the common components of water-based lubricants has been established
using HRMS and tandem mass spectrometry to enable identification of personal
lubricant formulations and differentiation between suppliers.
PMID- 29964358
TI - The Gosport War Memorial Hospital Panel report and its implications for nursing.
PMID- 29964356
TI - Chronic differences in white matter integrity following sport-related concussion
as measured by diffusion MRI: 6-Month follow-up.
AB - Recent studies demonstrated evidence of physiological changes in the brain
following sport-related concussion (SRC) that persisted beyond the point at which
athletes achieved full symptom recovery. Diffusion MRI techniques have been used
to study brain white matter (WM) changes following SRC; however, longitudinal
studies that follow injured athletes from the acute to chronic stages of injury
are sparse. The current study explores potential persisting effects of the
injury, which serves as a follow-up to our previous work that reported WM changes
in the acute and subacute phase of SRC recovery. Concussed high school and
collegiate football players (n = 17) and well-matched teammate controls (n = 20)
were followed up at 6 months postinjury with diffusion tensor (DTI) and diffusion
kurtosis imaging (DKI) as well as measures of self-reported symptoms, cognitive
functioning, and balance. Results of tract-based spatial statistics (TBSS)
analyses revealed continued widespread decreased mean and axial diffusivity
compared to control subjects in 6-month follow-up scans. On the other hand,
kurtosis metrics, which were significantly higher in concussed athletes in the
acute phase, had normalized. WM tract regions-of-interest (ROIs) were created
from significant clusters in the TBSS analysis, and linear mixed effects (LME)
analyses were used to look at longitudinal changes in these ROIs over time. LME
analyses revealed few time * group interactions indicating findings were
relatively stable over time. In addition, acute concussion symptoms predicted
diffusivity measures at 6 months postinjury. Findings indicate that DTI and DKI
may be useful tools in assessing concussion severity, recovery, and possible long
term effects of concussion.
PMID- 29964359
TI - Cyclopentene Annulations of Alkene Radical Cations with Vinyl Diazo Species Using
Photocatalysis.
AB - A direct (3+2) cycloaddition between alkenes and vinyl diazo reagents using
either Cr or Ru photocatalysis is described. The intermediacy of a radical cation
species enables a nucleophilic interception by vinyl diazo compounds, a departure
from their traditional electrophilic behavior. A variety of cyclopentenes are
synthesized using this method, and experimental insights implicate a direct
cycloaddition instead of a cyclopropanation/rearrangement process.
PMID- 29964361
TI - Endoscopic endonasal surgery to correct congenital obstruction of the lacrimal
pathway.
PMID- 29964360
TI - Adapting management to a changing world: Warm temperatures, dry soil, and
interannual variability limit restoration success of a dominant woody shrub in
temperate drylands.
AB - Restoration and rehabilitation of native vegetation in dryland ecosystems, which
encompass over 40% of terrestrial ecosystems, is a common challenge that
continues to grow as wildfire and biological invasions transform dryland plant
communities. The difficulty in part stems from low and variable precipitation,
combined with limited understanding about how weather conditions influence
restoration outcomes, and increasing recognition that one-time seeding approaches
can fail if they do not occur during appropriate plant establishment conditions.
The sagebrush biome, which once covered over 620,000 km2 of western North
America, is a prime example of a pressing dryland restoration challenge for which
restoration success has been variable. We analyzed field data on Artemisia
tridentata (big sagebrush) restoration collected at 771 plots in 177 wildfire
sites across its western range, and used process-based ecohydrological modeling
to identify factors leading to its establishment. Our results indicate big
sagebrush occurrence is most strongly associated with relatively cool
temperatures and wet soils in the first spring after seeding. In particular, the
amount of winter snowpack, but not total precipitation, helped explain the
availability of spring soil moisture and restoration success. We also find
considerable interannual variability in the probability of sagebrush
establishment. Adaptive management strategies that target seeding during cool,
wet years or mitigate effects of variability through repeated seeding may improve
the likelihood of successful restoration in dryland ecosystems. Given consistent
projections of increasing temperatures, declining snowpack, and increasing
weather variability throughout midlatitude drylands, weather-centric adaptive
management approaches to restoration will be increasingly important for dryland
restoration success.
PMID- 29964362
TI - Evaluation of the Effects of Apatinib on the Pharmacokinetics of Venlafaxine and
O-desmethylvenlafaxine in SD Male Rats by UPLC-MS/MS.
AB - The objective of this study was to evaluate the effect of apatinib on the
pharmacokinetics of venlafaxine and O-desmethylvenlafaxine in SD rats and the
inhibitory effects of apatinib on venlafaxine in rat and human liver microsomes.
Twenty-one SD male rats were randomly divided into three groups (n = 7): group A
(multiple dose of 40 mg/kg apatinib for 7 days), group B (single dose of 40 mg/kg
apatinib) and group C (the control group). All samples were measured by UPLC
MS/MS. The results indicated that a single dose of apatinib increased the AUC(0
t) , AUC(0-infinity) and Cmax of both venlafaxine and O-desmethylvenlafaxine
significantly, while Vz/F and CLz/F were decreased. As for group A, only AUC(0-t)
and CLz/F of venlafaxine were changed, while no parameters of O
desmethylvenlafaxine were altered. In addition, apatinib was determined to be a
mixed inhibitor of venlafaxine.
PMID- 29964363
TI - A Porous Organic Poly(triphenylimidazole) Decorated with Palladium Nanoparticles
for the Cyanation of Aryl Iodides.
AB - A new porous organic poly(triphenylimidazole), PTPI-Me, was prepared through a
Yamamoto self-coupling reaction of 2,4,5-tris-(4-bromophenyl)-1-methyl-1H
imidazole (TPI-Me) in the presence of bis(1,5-cyclooctadiene)nickel(0). The
polymer was subsequently decorated with Pd nanoparticles (NPs) to afford a
heterogeneous cyanation catalyst, Pd@PTPI-Me. Pd NPs with an average diameter of
2.7 nm were grown within the PTPI-Me framework, owing to the coordination of the
imidazole rings to the Pd species. The resultant Pd@PTPI-Me catalyst, with a Pd
loading of 0.13 mmol g-1 , exhibited superior catalytic activity for the
cyanation of aryl iodides. More importantly, the heterogeneous catalyst was also
readily recycled and displayed negligible deactivation after five cycles.
PMID- 29964364
TI - The effectiveness of aromatherapy and massage on stress management in nurses: A
systematic review.
AB - AIMS AND OBJECTIVES: To assess the effectiveness of aromatherapy and massage on
relieving stress in nurses. BACKGROUND: Nurses face uncommon levels of stress in
medical settings. Stress has a negative impact on nurses' well-being and the
organisation where they work. Aromatherapy and massage are important strategies
for stress reduction. However, the effectiveness of aromatherapy and massage on
relieving stress in nurses currently lacks understanding. DESIGN: Systematic
review. METHOD: We performed a quantitative systematic review using Cochrane
methods. We searched existing literature in the following databases: PubMed,
PsycINFO, Embase, Web of Science and Cochrane Library, to examine any
experimental design studies published from the earliest date available to August
2017 in English. Risk of bias per outcome was assessed. RESULTS: A total of 10
articles met the inclusion criteria, including aromatherapy (n = 4), massage (n =
4) and aromatherapy massage (n = 2). Most studies reported that aromatherapy and
massage exert a beneficial effect on the stress of nurses. One study showed that
the aromatherapy massage with music interventions has no effect on the stress of
nurses. However, the number of the studies is limited and has high or unclear
risk of bias. CONCLUSION: This review revealed that the evidence does not
sufficiently prove that aromatherapy, massage and aromatherapy massage are
effective for reducing job-related stress of nurses. We need to conduct high
quality studies to verify the effects of these interventions on nurses' stress
levels in the future. Moreover, we need to integrate outcome measures of stress
levels for developing more appropriate tools than the ones used as present.
RELEVANCE TO CLINICAL PRACTICE: Nurses' stress has a negative impact on their own
and organisation where they work. All available opportunities should be taken to
reduce nurses' stress. It will be beneficial for nurse shortage.
PMID- 29964365
TI - Living anatomy of the pulmonary root.
PMID- 29964367
TI - Generation and Application of (Diborylmethyl)zinc(II) Species: Access to
Enantioenriched gem-Diborylalkanes by an Asymmetric Allylic Substitution.
AB - We report the successful generation of (diborylmethyl)zinc(II) species by
transmetallation beteween isolable (diborylmethyl)lithium and zinc(II) halide
(X=Br, Cl) and their application in the synthesis of enantioenriched gem
diborylalkanes bearing a stereogenic center at the beta-position of the diboryl
groups by an asymmetric allylic substitution reaction. The reaction has a broad
substrate scope, and various enantioenriched gem-diborylalkanes can be obtained
in good yields with excellent enantioselectivity. Further elaboration of the
enantioenriched gem-diborylalkanes provides access to a diverse set of valuable
chiral building blocks.
PMID- 29964368
TI - Incidence and risk factors of incontinence-associated dermatitis among patients
in the intensive care unit.
AB - OBJECTIVE: To investigate the incidence of incontinence-associated dermatitis
(IAD) among patients in the intensive care unit (ICU) and to identify potential
risk factors to establish a reference for clinical nursing work. BACKGROUND:
Patients in the ICU are susceptible to IAD. IAD is painful, reduces the patient's
quality of life and adds to the workload of clinical medical staff. However, risk
factors associated with IAD may differ between countries and healthcare settings.
DESIGN: Prospective cohort study METHODS: From November 2016 to November 2017, a
prospective cohort study was conducted among109 patients in three Class 3, Grade
A hospitals (comprising 9 ICUs in total) in Beijing. The Incontinence-associated
Dermatitis and Its Severity (IADS) instrument in Chinese was applied to assess
IAD. Univariate and multivariate logistic regression analyses were performed to
identify risk factors for IAD. RESULTS: The study population had 29 community
acquired and 80 nosocomial infections, and 26 (incidence: 23.9%) of these had
IAD. On univariate analysis, a significant difference was observed between
patients with and without IAD with respect to the following indices: Barthel
index, Braden scale score, Nutritional Risk Screening 2002 (NRS2002) score, serum
albumin level, occurrence of infection, faecal incontinence, frequency of faecal
incontinence, stool property and double (faecal and urinary) incontinence and
perineal assessment tool (PAT) score (p < 0.05). Multivariate logistic regression
analysis showed that three factors entered the regression equation-that is, the
Braden Scale Score, serum albumin level and double incontinence. Of these, the
Braden Scale Score and serum albumin level were protective factors for IAD. Thus,
the higher the Braden Scale Score, the lower the risk of IAD (OR = 0.678, 95%
confidence interval [CI] = 0.494-0.931); a higher level of serum albumin implies
a lower risk of IAD, provided it is within the normal range (OR = 0.884, 95%CI =
0.797-0.981). Double incontinence was an independent risk factor for IAD (OR =
10.512, 95% CI = 2.492-44.342). CONCLUSION: A higher morbidity of IAD is seen in
the ICU. Specific preventive and nursing measures are required to maintain the
skin integrity of critically ill patients in daily nursing practice to improve
patient quality of life and the quality of nursing care. RELEVANCE TO CLINICAL
PRACTICE: Incontinence-associated dermatitis is characterised by inflammation and
tissue damage due to prolonged/repeated exposure to urine and/or stool. Not every
patient with urine and/or stool incontinence develops IAD. Medical staff can use
research-based evidence to identify ICU patients at risk of IAD to reduce
morbidity and improve health outcomes.
PMID- 29964370
TI - ERRATUM: Cloud Computing for Pharmacometrics: Using AWS, NONMEM, PsN, Grid
Engine, and Sonic.
PMID- 29964369
TI - Controllable 1D and 2D Cobalt Oxide and Cobalt Selenide Nanostructures as Highly
Efficient Electrocatalysts for the Oxygen Evolution Reaction.
AB - The relationship between controllable morphology and electrocatalytic activity of
Co3 O4 and CoSe2 for the oxygen evolution reaction (OER) was explored in alkaline
medium. Based on the time-dependent growth process of cobalt precursors, 1D Co3
O4 nanorods and 2D Co3 O4 nanosheets were successfully synthesized through a
facile hydrothermal process at 180 degrees C under different reaction times,
followed by calcination at 300 degrees C for 2 h. Subsequently, 1D and 2D CoSe2
nanostructures were derived by selenization of Co3 O4 , which achieved the
controllable synthesis of CoSe2 without templating agents. By comparing the
electrocatalytic behavior of these cobalt-based catalysts in 1 m KOH electrolyte
toward the OER, both 2D Co3 O4 and 2D CoSe2 nanocrystals have lower
overpotentials and better electrocatalytic stability than that of 1D
nanostructures. The 2D CoSe2 nanosheets require overpotentials of 372 mV to reach
a current density of 50 mA cm-2 with a small Tafel slope of 74 mV dec-1 . A
systematic contrast of the electrocatalytic performances for the OER increase in
the order: 1D Co3 O4 <2D Co3 O4 <1D CoSe2 <2D CoSe2 . This work provides
fundamental insights into the morphology-performance relationships of both Co3 O4
and CoSe2 , which were synthesized through the same approach, providing a solid
guide for designing OER catalysts.
PMID- 29964371
TI - [PREVALENCE OF AND POSSIBLE RISK FACTORS FOR PROLONGED HOSPITAL STAY IN
DEPARTMENTS OF INTERNAL MEDICINE].
AB - BACKGROUND: Prolonged hospitalization (PH) is associated with increasing rates of
complications and cost. OBJECTIVES: To detect and quantify causes and predictors
for PH in current practice. METHODS: PH was defined as higher than the 70th
percentile of the mean hospitalization duration for each department (two medical
departments and one acute geriatric ward). Demographic and clinical data were
collected on admission in order to determine predictive factors for PH. Actual
causes for PH were tested on the 4th day of hospitalization for all patients by:
(1) questioning the patients' attending physicians using a structured
questionnaire; (2) assessing the patients' charts using a validated tool.
RESULTS: Data were collected during a 5-month study period for all 1092
consecutively admitted patients hospitalized in the three departments in the
study of whom 337 (30%) had a PH. In the multivariate analysis we detected the
following independent predictors for PH: (1) unmarried patients; (2) dependent
patients; (3) hospitalization in the geriatric versus medical department; (4) an
expected high mortality rate according to a validated prediction score; (5) renal
failure on admission; (6) prior admission in the previous 6 months. The disease
leading to the current admissions was the reason for continued admission on day 4
in the patients with eventual PH in 85% of the cases, as compared to 93% in the
control group with regular-duration of hospitalization (p=0.014). On day 4, non
medical reasons for prolonged duration were detected in 7% of those with eventual
PH as compared to 1% in the control group (p=0.018). CONCLUSIONS: We already
detected demographic and clinical predictors for PH on admission, some of which
may be amenable to intervention.
PMID- 29964372
TI - [CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA - CASE REPORT].
AB - INTRODUCTION: Pediatric sudden death is a devastating problem worsened by the
fact that the death may have been preventable. Sudden cardiac death (SCD) defined
as unexplained death within 1 hour after the onset of witnessed symptoms or
within 24 hours from the moment when the decedent was last seen alive in the
absence of symptoms or any obvious non-cardiac causes. Pediatric sudden cardiac
arrest can result from a variety of cardiac conditions such as genetic/heritable,
trauma, or use of medications/drugs. The sentinel event can be fatal.
Fortunately, not all cases are fatal and suspicion may be evoked by symptoms,
known family history, or findings on physical examination. Understanding these
features and appropriate referral can improve survival. Catecholaminergic
polymorphic ventricular tachycardia (CPVT) is a highly malignant inheritable
cardiac channelopathy associated with the potentially life-threatening
catecholamine-mediated ventricular arrhythmias triggered by stress or exertion.
CPVT constitutes a substantial portion of pediatric SCD, therefore recognition
and correct management are of vital importance. The past decade and a half has
provided exciting new discoveries elucidating the genetic etiology and
pathophysiology of CPVT. This knowledge improves our approach to diagnosis and
management of the disease. In this article we bring the tragic story of a little
girl who died suddenly due to CPVT. We try to summarize our understanding of the
genetic etiology, the molecular pathogenesis and the current approach to
diagnosis and management of CPVT.
PMID- 29964373
TI - [SELECTING A SPECIALTY BY INTERNS IN A CHANGING PERIOD: A MULTI-YEAR AND SINGLE
CENTER EXPERIENCE].
AB - AIMS: To collect data on the expectations of interns at the onset of their
internship regarding their professional future and the actual realization of
these expectations of medical graduates who completed their internship in one
medical center during the years 2010-2015. BACKGROUND: The internship year may
have great importance in the decision-making process regarding selection of
future residency. Previous research conducted 10-20 years ago involved graduates
of Israeli medical schools. In the current era up to 50% of interns are foreign
medical graduates (FMG), and it is not clear whether all of these professionals
find a residency or employment according to their wishes. METHODS: Our hospital's
database includes demographic details of all 237 graduates of the aforementioned
years, according to gender (64% male); medical school (Israeli 50%); and
ethnicity (Jewish, 66%). The aim of the study was to call all graduates according
to the telephone numbers in the database and obtain relevant information on the
basis of a pre-arranged script and with a standardized questionnaire to achieve
uniform collection of data. RESULTS: Of 237 graduates, 151 (64%) responded, of
whom 101 (64%) were male, 90 (60%) were Jewish, and 80 (54%) were FMG. Most
interns had decided on a future career at the onset of their internship (114,
75%), but at its completion this rate had decreased to 88 (59%). Their
preferences included surgical specialties 40 (36%), pediatrics 34 (30%), internal
medicine 22 (19%), family practice 9 (8%), and other specialties 8 (7%). At the
conclusion of the internship 108 (75%) immediately started a residency program;
the remainder started employment in the community not within the context of a
residency. A high degree of satisfaction was examined for three factors: personal
relations and ethics - 114 (76%), professional learning - 108 (72%) and
counseling regarding their professional future - 46 (31%). At the onset of their
internship,) 75 77%( of the men and 46 )75%( of the women had decided upon their
future career, without major change by the year's end. In reality, 43 (84%) of
the women started a residency, but only 63 (65%) of the men (p=0.013). At the
start of the year 67 (77%) of the Jewish interns and 46 (75%) of the Arab interns
had decided on a future career; at the end of the year, the rate for Jewish
interns had increased to 74 (85%) and it had decreased to 31 (67%) for Arab
interns (p=0.026). Of the Jewish sector 74 (85%) had actually started a
residency, as compared to 33 (54%) of the Arab sector (p<0.001) and 26 (43%) Arab
graduates started work in the community not within the context of a residency.
The rate of Israeli graduates who at onset of their internship had decided on
their future choice was similar to that of FMG, 55 (82%) as compared to,
respectively, 58 (73%) (Non significant), but at the end of the year a
significant gap had opened up, 47 (86%) vs. 40 (52%), respectively (p=0.04). In
addition, and not surprisingly, there were significant differences in the three
measures of satisfaction between the Israeli and foreign graduates. CONCLUSIONS:
During the internship year significant differences emerge between the interns,
according to gender, ethnic background or the country they had studied medicine.
Improved counseling could possibly help interns to secure optimal employment,
especially for foreign medical graduates.
PMID- 29964374
TI - [FAMILY, IMMIGRATION AND QUALITY OF TREATMENT: GENETIC AND ENVIRONMENTAL EFFECTS
ON COMPLICATIONS IN DIABETES].
AB - BACKGROUND: There is a variety of native and foreign-born diabetes patients from
all over the world in Israel. A combination of genetic and acquired factors leads
to high-rate spreading of diabetes mellitus. Consequently, certain differences
exist in a number of features of the disease typical for Israeli-born patients
and for immigrants. METHODS: This retrospective research has been conducted
within a population of diabetes patients aged over 40 years in a group of
immigrant and a group of Israeli-born patients (119 immigrants and 65 Israeli
born patients). Parameters checked were: background diseases, family history,
types of treatment, risk factors and complications. RESULTS: In the group of
immigrants, the percentage of male patients with negative family history was much
higher than the percentage of male patients with positive family history of
diabetes mellitus (16.8% vs. 6.5% respectively). Relating immigrants with
positive family history, micro-vascular complications were 3 times more prevalent
than macro-vascular complications (30.3% vs. 9.2% respectively). In the group of
Israeli-born patients there was a significant difference in the level of micro-
and macro-vascular complications among the patients with positive and negative
family history (32% vs. 12.3% for macro-vascular and 27.7 vs. 10.8% for micro
vascular complications). CONCLUSIONS: (1) The percentage of males suffering from
diabetes mellitus with negative family history is much higher than that with
positive family history (16.8% vs. 6.5%); (2) The level of micro-vascular
complications among immigrants with positive family history is 3.3 times higher
than the level of macro-vascular complications among immigrants with positive
family history of diabetes mellitus (30.3% vs. 9.2%).
PMID- 29964375
TI - [WHY ARE SOME OF THE HOSPITALIZATIONS LENGTHS IN ISRAEL SO LONG?]
AB - INTRODUCTION: Prolonged hospitalizations are a major challenge for any society
and to the Israeli health system in particular. Identifications of predictors
underlines the areas that require comprehensive interventions to prevent long
hospital stays. Analysis of the literature points out that discharges from
internal medicine wards should be preplanned and coordinated. It is obvious that
the care of those with special needs such as the elderly, dependent, lonely,
disabled and patients with comorbidities mandates the development of proper
community-based care that will be a continuation of in-hospital therapy. It seems
inevitable that this urgent need will require a medical professional whose main
task will be coordination of care in and out of the hospital.
PMID- 29964376
TI - [HOSPITAL ACCREDITATION - TIME FOR RETHINKING?]
AB - INTRODUCTION: Accreditation provides an incentive to promote processes improving
quality and enhancing patient safety, both in hospital and community settings.
For the past three decades, many western, as well as developing countries, have
adopted this methodology. Israel too has taken this pathway to adopt
accreditation in general, geriatric and psychiatric hospitals as part of a
national mission. Beyond the benefits to the patient, accreditation has numerous
advantages: raising the professional accountability of healthcare providers,
defining targets for improvement based on the strategies of the Ministry of
Health and specifying standardization of care and regulations. Accreditation
guides care-givers to develop insights on the quality and perception of
innovation and facilitates trust, workers' coherence and teamwork. Alongside
these benefits, thoughts about the future of the process arise: A variety of
accreditation programs exists around the world, while several governments
implement other incentives for healthcare system improvement- such as quality
indices. Moreover, professionals resist this methodology, which may be considered
to be over-complex to maintain. Since we have already assimilated concepts,
perspectives, knowledge and experience in this challenging process, the outlook
for preserving a nationwide hospital-based accreditation in the current format
should be re-examined, in order to establish a long-lasting quality mechanism.
PMID- 29964377
TI - [EPIGENETIC MECHANISMS IN MODELS OF CHRONIC PAIN - A TARGET FOR NOVEL THERAPY?]
AB - INTRODUCTION: Evidence of epigenetics' role in pain response is accumulating in
recent years. Tightly regulated epigenetic alterations on DNA and histones in the
sensory circuit shape the physiological response to injury. Altering those
epigenetic processes hinders therapeutic potential in pain. This review provides
an overview of epigenomic modification in the development of chronic pain, and
summarizes the therapeutic potential to alter epigenetic processes.
PMID- 29964378
TI - [THE RELATIONSHIP BETWEEN HEARING LOSS AND COGNITIVE DECLINE IN THE ELDERLY AND
THE EFFICIENCY OF HEARING REHABILITATION IN PREVENTING COGNITIVE DECLINE].
AB - INTRODUCTION: The population of elderly patients in Israel is constantly
increasing, and so is the prevalence of age-related morbidities. Age-related
hearing loss is very common, affecting approximately a third of the population
over 65 years of age. Dementia is also common in elderly patients, and its
prevalence doubles every 5 years after the age of 65 years. Hearing loss has many
negative effects, such as decreased quality of life, social isolation and
depression. In the last two decades, researchers had shown a direct relationship
between hearing loss and dementia. Successful hearing rehabilitation can mitigate
these negative effects and recent studies demonstrated that rehabilitation with
cochlear implants slowed cognitive decline. In most cases, hearing aids are used
for rehabilitation. However, for many patients, conventional hearing aids are
insufficient. Cochlear implants were found to be effective and safe for elderly
patients with severe hearing loss, but commonly they do not refer for evaluation
due to their age. In this review we present the scientific evidence regarding the
negative effects of age-related hearing loss, the association between hearing
loss and cognitive decline, and the role of cochlear implantation in improving
quality of life and slowing cognitive decline.
PMID- 29964379
TI - [PERINEAL TEARS THAT INVOLVE THE ANAL SPHINCTER - IS IT AN UNPREVENTABLE
OBSTETRIC PROBLEM AND WHAT ARE ITS REPRECUSSIONS?]
AB - INTRODUCTION: Perineal tears that involve the anal sphincter, especially those
which are occult, are common in cases of vaginal delivery or instrumental
deliveries. Parturients who experience such types of perineal tears may suffer
from flatus or fecal incontinence and also fistula to various surrounding organs.
There is no consensus in the relevant medical literature regarding the risk
factors for the development of these tears, as contradictive results are
presented in various relevant studies. Traditional methods for perineal
protection, executed by midwives, such as perineal massage with oil, have also
failed to be proven as an effective measure for that purpose. The only theme on
which there appears to be a consensus is the fact that protective episiotomy is
not helpful in protecting the perineum during vaginal delivery. The inability to
predict which parturient will have a perineal tear that involves the anal
sphincter, as well as the lack of predictive measures to avoid their occurrence,
drive more and more women to demand and receive cesarean section by maternal
request, which is accepted by most obstetricians nowadays.
PMID- 29964380
TI - [ACCREDITATION IN HOSPITALS: ATTITUDES AND SATISFACTION OF STAFF MEMBERS FROM THE
PROCESS].
AB - INTRODUCTION: The accreditation process is an inseparable part of the healthcare
system in many countries around the world and is an important part of the quality
of care process. The team's collaboration is essential for completing the
accreditation process. Therefore, their satisfaction with the process and
attitudes toward it may influence its effective implementation in the short and
long term. The purpose of this literature review was to describe the
accreditation process, its advantages versus its shortcomings, and to present the
research findings regarding the attitudes and satisfaction of the staff members
in the process. The findings showed that staff attitudes toward the accreditation
process are important for its implementation. The audit process has witnessed
many positive and negative aspects that have a different effect on the
satisfaction and attitudes of the staff at different points of time and different
perspectives. In summary, despite the opposing positions of staff in the
accreditation process in various studies, it seems that the staff's attitudes and
satisfaction with the accreditation process is generally higher than low,
although this can't be categorized unequivocally. For this, a deeper
investigation is required, based on valid and reliable measurement tools.
PMID- 29964382
TI - [A Clinical Department as a Closed Budget Unit].
PMID- 29964381
TI - [HAMSTRING STRAIN INJURIES IN SPORTSMEN].
AB - INTRODUCTION: Acute hamstring strain injuries are common in sports that involve
sprinting, kicking, jumping or high-speed skilled movements. Despite increased
knowledge of hamstring muscle injuries, the incidence has not diminished. It is
generally believed that they happen during the terminal swing phase of the gait
cycle. Most hamstring injuries occur along the proximal musculo-tendon junction,
where the muscle fibrils intersect with the tendon, but may occur anywhere
between the origin and the insertion. A number of potential risk factors have
been proposed for hamstring strain, among them fatigue, lack of flexibility,
imbalance of muscular strength with a low hamstring to quadriceps ratio, and
insufficient warm-up. Certain types of hamstring injuries are more likely to
require prolonged rehabilitation and delayed return to play. An emphasis on neuro
muscular control and eccentric strengthening of the involved muscles is suggested
for the successful return to sport after injury.
PMID- 29964383
TI - [THE USE OF FUNCTIONAL TESTS IN FITNESS FOR WORK ASSESSMENTS IN THE RESPONSA
LITERATURE].
AB - INTRODUCTION: Employment-related performance tests have been known since ancient
times. In this article, we have demonstrated how functional tests were used in
the responsa literature over years, when making decisions on the ability of
working people. In contrast to the conservative approach that exists in the
responsa literature, according to which the very existence of the eclipse of
tremor in the hands leads to the disqualification of a shohet or mohel from
continuing his work without taking into account other variables, individual
fitness decisions were presented which used functional tests or visited the
employee's place of work in order to determine his ability to continue working.
The use of functional tests as described in the responsa literature is also of
great importance in the world of the occupational doctor's practice in the modern
era.
PMID- 29964384
TI - [THE CONSTRUCTION OF THE EDITH WOLFSON HOSPITAL IN HOLON-ISRAEL].
AB - INTRODUCTION: For seventeen years the frame of the hospital building in Tel
Gibborim, Holon, was abandoned due to severe financial disorders. The Hospital
was projected to serve patients from Holon and Bat Yam. Only in 1981 was it
opened to the inhabitants of those cities. The contributor, Sir Isic Wolfson, and
his Family, were present at the opening ceremony.
PMID- 29964385
TI - [SUMMARY OF THE EPICOH 2017 - EPIDEMIOLOGY AND OCCUPATIONAL HEALTH - EDINBURGH
2017].
PMID- 29964386
TI - ?
PMID- 29964387
TI - ?
PMID- 29964388
TI - [Retroperitoneal mixed malignant mullerian tumor : exceptional localisation and
prognosis].
AB - Primary retroperitoneal carcinosarcoma or mixed malignant mullerian tumor (MMMT)
is an extremely rare clinical entity. These aggressive tumors arise most commonly
from genital tract. The retroperitoneal location is exceptional. Here we report
the case of a 63-years old female diagnosed with heterologous, extra-genital,
retroperitoneal carcinosarcoma, with malignant cells in the ascitic fluid and
extra-ovarian metastatic implants. She was treated with complete radical surgical
treatment consisting of resection of the retroperitoneal tumor, with omentectomy,
hysterectomy, bilateral salpingooophorectomy and lumbo-aortic and pelvic
lymphadenectomy. She received adjuvant chemotherapy with 6 cycles of Carboplatin
and Paclitaxel. She is in complete clinical and radiological remission since the
end of chemotherapy, for a total of 113 months. To our knowledge, this is the
longest reported disease free survival of the extra-genital retroperitoneal MMMT.
This case and the review of the literature illustrate the importance of surgical
treatment. However, there are no evidence-based guidelines for the systemic
management of these tumors.
PMID- 29964389
TI - [A rare case of hepatotoxicity in geriatrics].
AB - We report a case of hepatotoxicity following the introduction of two drugs to
treat a 81 years old man. The presence of liver alterations following the
introduction of a new drug must suggest an adverse drug reaction. Manifestations
of adverse drug reactions are often non-specific. Thus, the most important
problem in assessing adverse drug reactions is establishing whether there is a
causal association between the suspected drug and the untoward clinical event.
The use of the Naranjo score could help the clinician to assess the probability
of a causal relationship between a drug and the suspected adverse drug reaction.
PMID- 29964390
TI - [An exceptional cause of automatic implantable defibrillator dysfunction].
AB - Twiddler syndrome is an exceptional cause of dysfunction of cardiac prostheses
resulting from a displacement of the probe either by deliberate or unconscious
manipulation. We report the case of a man admitted for a respiratory arrest (ACR)
caused by an extreme bradycardia. Initially implanted 6 weeks earlier for
idiopathic ventricular fibrillation without documented ischemic causes or major
conduction disorders. The patient has benefited from extraction with
reimplantation of a new defibrillation probe. The originality of this observation
is underlined by the occurrence of a previously unrecognized inaugural syncopal
atrioventricular block revealing Twiddler syndrome in a patient initially
implanted with a secondary prevention defibrillator for idiopathic ventricular
fibrillation.
PMID- 29964391
TI - [Hoffmann syndrome : about two new cases].
AB - Hypothyroidism is exceptionnally revealed by hypertrophic myopathy, known as
Hoffmann syndrome. We report two new cases of severe hypothyroidism presenting as
hypertrophic myopathy, occurring in two men of 49 and 57 years-old.
PMID- 29964392
TI - [Bleeding induced by Selective Serotonine Reuptake inhibitors (SSRI). Case report
and review of literature].
AB - Selective serotonin re-uptake inhibitors are widely prescribed on a daily basis
due to their recognized efficiency and their few side effects as opposed to
tricyclic antidepressants. The iatrogenic effect mainly causes benign hemorrhagic
episodes however some cases could get serious. The Belgian centre of
pharmacotherapeutical information warns prescribing physicians regarding the use
of SSRIs. The existing risk of cutaneo-mucosal bleeding or other forms of
hemorrhage due to SSRIs has been identified in the early 90s based on reported
cases. Since then, cohort epidemiology studies or case studies have shown a
correlation between the SSRIs intake and bleeding, linked to inhibition of the
serotonin re-uptake (5HT). We report 2 clinical cases of patients who presented
hemorrhages. One has been taking sertraline and the other fluoxetine. Through
this literature review, we aim at discussing the impact of the different
physiopathologic mechanisms.
PMID- 29964393
TI - ?
PMID- 29964394
TI - ?
PMID- 29964395
TI - [Scavenging Effect of Rime and East Wind on PM2.5 Under Air Heavy Pollution in
Beijing].
AB - In order to study the scavenging effect of rime and east wind on the
concentrations of PM2.5 in Beijing during the air heavy pollution, PM2.5
concentration data of some mountains and plains stations was used, together with
meteorological data, wind profile data, aerosol extinction coefficient radar data
collected during December 19 to 27, 2015, to analyze the clearance mechanisms of
rime and east wind on PM2.5.The results showed that 1the removal of PM2.5 by rime
was a different mechanism from that by the north wind and rainy weather, in the
cooling conditions, the droplets touched the branches, wire for solid
condensation, leading to formation of rime, and the concentration of PM2.5
decreased;2the east wind is a special kind of wind in Beijing area, when easterly
wind decreased with height, a strong upward motion could be formed, and the PM2.5
was uplifted from the surface layer to the top, while with larger westerly wind
in top, it was removed into downstream and cleaned; when east wind increased with
height, a weak downward movement was easy to form, and when this sinking motion
could not reach the ground, the surface layer of PM2.5 capacity became small,
which was beneficial to increase the concentration of PM2.5;3the PM2.5scavenging
ability of east wind depended on two points, one was the strength and development
of upward movement of the height formed by the east wind, and the second was the
initial height of uplifted motion formed by east wind, the lower the origin of
the ascending motion height, the more obvious the removal of PM2.5;4after
occurrence of east wind, along with the ascending motion to m.s-1 magnitude, the
mixed layer height increased to 1200-1800 meters, and PM2.5 was uplifted to top
layer and cleaned.
PMID- 29964396
TI - [Impact of Collision Removal of Rainfall on Aerosol Particles of Different
Sizes].
AB - The impact of collision removal of rainfall on aerosol particles of different
sizes was analyzed through the calculation of Stokes number, combining with the
hourly PM2.5 concentrations and meteorological data in Haidian from October 2012
to October 2014, and also the size distribution data in a selected rainfall
process. The calculation results of Stokes number showed that the raindrops had
little effect on direct collision removal of aerosol particles of smaller than 2
MUm, and had more effect on aerosol particles of larger than 2 MUm. Based on the
statistical analysis of the observation data, the precipitation processes or the
precipitation hours with significantly decreased PM2.5 were quite limited.
However, PM2.5 concentrations were increased in 43.2% of the precipitation hours.
By analyzing the size distribution data of aerosol particles during a typical
precipitation process, we found that the precipitation had significant scavenging
effect on Aitken mode particles (<0.1 MUm) and coarse mode particles (>1.0 MUm),
except for the accumulation mode particles. Since the accumulation mode aerosols
contributed most of the mass of PM2.5, the rainfall processes only had minor
influence on the collision scavenging of PM2.5.
PMID- 29964397
TI - [Source Apportionment and Health Risk Assessment of VOCs During the Haze Period
in the Winter in Beijing].
AB - A method for determining volatile organic compounds (VOCs) by cryogenic dynamic
adsorption in solid adsorbent tubes, subsequent thermal desorption with
cryofocusing in a cold trap and analysis by gas chromatography and mass
spectrometry was adapted for continuous ambient air monitoring. VOCs pollution
characteristics and health risk assessment (HRA)were researched in detail.
Moreover, the sources apportionment was reliably analyzed by positive matrix
factorization (PMF) model. The results showed that the average concentration of
VOCs was 332.34 MUg.m-3 per day, the concentrations of aromatic hydrocarbon and
halo hydrocarbon were remarkably high compared to the other VOCs. Particularly,
the PMF analysis results revealed that solvent/paint use emission, biomass or
coal combustion and motor vehicle exhaust emissions were the main pollutants
emission sources. Additionally, the cancer risk index of all carcinogenic
substances was higher than the suggested value of USEPA(1*10-6), which could
cause potential harm to human health.
PMID- 29964398
TI - [Pollution Characteristics and Emission Coefficient of Volatile Organic Compounds
from Shoe-making Industry in Zhejiang Province].
AB - To explore the pollution characteristics and emission coefficient of volatile
organic compounds (VOCs) released from the shoe-making industry in Zhejiang
province, this paper used the survey data of 490 shoe enterprises obtained in
2015 to analyze the current VOCs treatment status of shoe-making industry, and
further screened 178 key enterprises to study the emission coefficient of shoe
making industry. The results showed that more than 95% of shoe enterprises failed
to effectively dispose VOCs, because most shoe enterprises did not have treatment
facilities. Moreover, solvent-based materials such as adhesive and primer were
still commonly used in approximately 90% of shoe-making industry. Meanwhile, the
main pollutants of VOCs in shoe-making industry were 2-butanone, toluene,
acetone, cyclohexanone, ethyl acetate, xylene, dichloromethane and cyclohexane.
Furthermore, the VOCs emission coefficient of shoe-making industry in Zhejiang
was 29.5 g-1, while it was affected by the production processes, and the cemented
construction techniques was higher than the injection techniques, which VOCs
emission coefficients were 35.9 g-1 and 23.8 g-1, respectively. Furthermore, the
major polluting stage of shoe-making industry was sole attaching, in which VOCs
emission coefficient could reach 20.8 g-1.
PMID- 29964399
TI - [Oxidative Capacity of the PM10 and PM2.5 in Beijing During 2014 APEC].
AB - In order to evaluate the effect of the joint air pollution prevention and control
program on the toxicity of the airborne particles in Beijing during the APEC
conference, we collected the PM10 and PM2.5 (particulate matter with aerodynamic
diameters of less than 10 MUm and 2.5 MUm respectively) from October to December
in the urban district of Beijing, and analyzed the oxidative capacity of the
particles by plasmid scission assay. The results indicated that the oxidative
capacity of PM10 was higher than that of PM2.5 during the APEC conference, and
that the damage rate of supercoiled DNA by the samples increased with their
experimental dose levels. The TD30 (toxic dose of PM causing 30% of plasmid DNA
damage, unit: MUg.mL-1) was used to indicate the oxidative capacity and the lower
TD30 values indicated higher oxidative capacity. The TD30 values of the PM
samples before, during, and after APEC conference displayed a descending order of
during APEC (November) >before APEC (October) >after APEC (December), which
indicated a decreasing order of the PM oxidative capacity of after APEC
(November) >before APEC (October) >during APEC. The TI (toxic index) was further
introduced to represent the human exposure risk of particles, which was
represented by the product of the mass concentration of PM (MUg.m-3) and the DNA
damage percentages under the PM dose of 250 MUg.mL-1 (%). Compared with the TI
values of previous years, the TI value of the 2014 APEC PM was lower than that of
2004, but higher than that of the 2008 Olypic Games, suggesting that the exposure
risk of airborne particles decreased obviously with the increase of policy
control strength.
PMID- 29964400
TI - [Concentration, Water-Soluble Ionic and Polycyclic Aromatic Hydrocarbons
Composition and Sources of PM2.5 During Summer in Hongshan District, Wuhan].
AB - Atmospheric PM2.5 samples were collected in Hongshan district, Wuhan from June
12th to July 22th, 2014. This study analyzed the characteristics and chemical
composition of PM2.5, and the concentrations of Polycyclic Aromatic Hydrocarbons
(PAHs) were analyzed by gas chromatography-mass spectrometry (GC-MS), to discuss
the pollution sources and formation mechanism. The results indicated the total
concentrations of PM2.5 ranged from 36.41 to 220.02 MUg.m-3, with the mean of
97.38 MUg.m-3. and the exceeding criteria rate was 59.26%. Furthermore, the
concentration of PM2.5 correlated significantly with wind speed in meteorological
parameters, when the wind speed increased, the concentration of PM2.5 showed a
trend of decline. The water-soluble ionic components of PM2.5 were SO42-, NO3-,
NH4+ and K+ which accounted for 40.67%, and the aerosol partial acid. The
influencing factors of formation process of SO42- were different from those of
NO3-, and NH4HSO4 and (NH4)2SO4 were the main compounds of NH4+ in PM2.5. The
average concentration of PAHs in PM2.5 was 11.30 ng.m-3, and the dominant
compounds were 4-6 ring PAHs. Industrial waste gas and vehicle emissions were the
sources of PM2.5. The various sources of the PAHs had contribution of 83.90% from
vehicle emission and combustion of coal, 10.17% from petroleum sources, and 5.08%
from coking emission. The concentration of toxic benzo[a]pyrene equivalent
(TEQBaP) ranged from 0.22 to 11.19 ng.m-3 (mean, 1.74 ng.m-3), and the exceeding
criteria rate was 7.41%.
PMID- 29964401
TI - [Statistical Characteristics of Urban Changzhou PM2.5 Based on k-means Analysis].
AB - Statistical analysis methods was utilized to investigate the variations of
monthly average concentrations of the six basic pollutants (SO2, NO2, CO, O3,
PM2.5 and PM10) of six national standard monitoring sites from 2013 to 2014 in
urban Changzhou. The results showed that, except for O3, SO2, NO2, CO, PM2.5 and
PM10 concentrations were all high in winter and low in summer. The relationship
between particulate matter and wind speed showed, with increasing wind speed, the
concentration of PM2.5 reduced. However, the concentration variations of PM10
were complicated and when wind speed increased, its concentration started to go
down and then elevated. Fast-cluster analysis (k-means) and the index of SWV &
DIV were used to classify the six basic pollutants into four clusters, and then
the relationship between gaseous pollutants and PM2.5in each cluster was
emphatically discussed by statistical analysis method. Four clusters were
assigned to fossil fuel combustion emissions (cluster1), O3 and secondary
aerosols (cluster2), incomplete combustion emissions and regional haze
(cluster3), urban city "background" (cluster4). Incomplete combustion cluster
accounted for the smallest percentage of urban Changzhou and city "background"
was cluster of urban Changzhou with the largest contribution. k-means analysis
results also showed that PM2.5 had complex sources in urban Changzhou.
PMID- 29964402
TI - [Comparison Test Between On-line Monitoring of Water-soluble Ions and Filter
based Manual Methods for PM2.5].
AB - Concentrations of water-soluble ions were measured in Beijing during 2014 for
comparison of URG online monitoring systems and filter-based manual methods. The
differences of four main ions components in spring, summer, autumn and winter
were compared. The total concentrations of eight ions measured by URG online were
higher than those of filter-based manual method. There was no significant
differences among the annual concentrations of Cl-,NO3-,Mg2+ and Ca2+ obtained by
the two methods, while the concentrations of SO42-,NH4+,Na+,K+ from online were
higher than those from filter. NO3-,SO42-,Cl- had good correlations in autumn and
winter, and NH4+ only had better fitting performance in winter.
PMID- 29964403
TI - [Chemical Composition of Water-soluble Ions in Smoke Emitted from Tree Branch
Combustion].
AB - Water-soluble ions in particulate matter (PM) from tree branch combustion were
determined. The results showed that the average content of total water-soluble
ions in flaming PM from dry branches was (28.88+/-17.54) g.kg-1. The major
components included Cl-, SO42-, and K+, the mean emission factors (EFs) of which
were in the range of 101.0 to 118.2 mg.kg-1. In addition, the mean content of the
total ions in smoldering PM was (6.38+/-2.79) g.kg-1. The main constituents
contained Na+, SO42-, K+, and Cl-, the mean EFs of which varied from 101.1 to
245.7 mg.kg-1. The average content of the total ions in flaming PM from green
branches was (22.13+/-13.52) g.kg-1. Their major components were SO42-, Cl-, and
K+, with mean EFs ranging from 136.4 to 197.6 mg.kg-1. Furthermore, the mean
content of all ions in smoldering PM derived from green branches was (15.71+/
19.09) g.kg-1. Cl-, SO42-, and Na+ were the main components, with mean EFs
varying from 298.6 to 869.1 mg.kg-1. Significant correlations were found between
the contents of Cl- and K+ in PM from dry and (or) green branches burned under
each condition. Similar relation also existed between EFs of Cl- from the dry
branches burned in smoldering condition and the moisture in them. The EFs of Cl-,
K+, and Mg2+ were positively correlated with moisture while the green branches
were burned in flaming condition. The EFs of Cl-, Na+, NH4+, and Mg2+ were
significantly positively correlated with moisture as well when the fuels were
combusted in smoldering condition. Combustion conditions, tree types, and
moisture in wood fuels all had impacts on the chemical compositions and EFs of
water-soluble ions in PM from tree branches. This may have significance in
estimating the quantity of the pollutants from forest fires.
PMID- 29964404
TI - [Number Concentration and Size Distribution of Particles Emitted by Light-duty
Gasoline Vehicles].
AB - In this study, three GDI (gasoline direct injection) and one PFI (port fuel
injection) light-duty gasoline vehicles were characterized for their particle
emission (number concentration and size distributions). Two condensation particle
counters (CPC) with different activation efficiencies (50% cut off diameter) were
used. It was found that the number concentration of particles emitted by GDI
gasoline vehicle was approximately one order of magnitude higher than that from
PFI gasoline vehicle. High emission of particles occurred within the first 200 s
of cold start. The number concentration of particles emitted from GDI vehicle was
largely influenced by the vehicle working condition, while that of PFI vehicle
was relatively stable despite of varying working conditions. The size
distributions of particles emitted from GDI and PFI vehicles had both nucleation
mode and accumulation mode. The peak diameter of nucleation mode particles was in
the range of 20-27 nm, while that of accumulation mode particle was in the range
of 80-95 nm. The number concentrations measured by the UCPC (50% cut off diameter
of 2.5 nm) were 35% (GDI) and 50.4% (PFI), respectively, higher than those
measured by the CPC (50% cut off diameter of 23 nm) used by the regulation.
PMID- 29964405
TI - [Testbed-Based Exhaust Emission Factors for Marine Diesel Engines in China].
AB - Water-borne transportation plays an important role in the economic and social
development and contributes greatly to air pollution in China as well. An
effective regulating policy is dependent on accurate estimation in terms of
sorts, quantification and location of emissions. However, there is insufficient
real and reliable data source for China's marine diesel engines and vessels. In
order to employ fuel-based approach and ship activity-based approach to estimate
accurately the exhaust emissions from water-borne transportation sector in China,
emission factors of different types of marine diesel engines were investigated.
Based on statistical analysis on Parent Engine emission test reports of 76 and
113 marine diesel engines manufactured by China's engine makers in accordance
with IMO NOx TierI and TierII standards respectively as defined in
MARPOL(International Convention for the Prevention of Pollution from Ships) Annex
VI, abnormal data were statistically identified and eliminated by Grubbs'
criterion method, fuel-based emission factors and energy-based emission factors
of NOx, CO, HC and CO2 for 2-Stroke main engines, 4-Stroke main engines and 4
Stroke auxiliary engines were determined respectively. The results showed that
fuel-based emission factors of NOx, CO, HC and CO2 for different types of marine
diesel engines were 30.67-76.55, 3.01-6.13, 1.25-2.24 and 3141.15-3165.63 kg.t-1
respectively. Energy-based emission factors of NOx, CO, HC and CO2 for different
types of marine diesel engines were 6.83-13.64, 0.61-1.35, 0.21-0.50 and 534.04
745.18 g.(kW.h)-1 respectively. In addition, the relationships of energy-based
emission factors against engine load were expressed by power function or
quadratic polynomial and the algorithm coefficients were determined. In addition,
it is difficult to obtain the true emission levels of marine diesel engines in
China through simple modification of emission factors reported by foreign
institutes. In particular,considering the diversity of diesel engines onboard
China's coastal and inland vessels, more samples and tests in terms of types and
operational conditions are necessary to provide basic data for marine emission
inventories in China. The results could provide applicable data for estimation of
marine emissions in China.
PMID- 29964406
TI - [Distribution, Source and Human Exposure of Phthalic Acid Esters (PAEs) in
Surface Dust in Urban Area of Xi'an City, China].
AB - A total of 58 surface dust samples were collected in urban area of Xi'an City.
High Performance Liquid Chromatography (HPLC) was used to analyze the
concentrations of six phthalic acid esters (PAEs) listed as priority pollutants
by United States Environmental Protection Agency (U.S. EPA). Composition,
distribution, environmental sources and exposure characteristics of PAEs in the
surface dust were further studied. All analyzed PAEs were detected in the surface
dust. The concentration of individual PAE compounds varied from not detectable to
183.19 mg.kg-1 and their mean concentrations decreased in the order of DEHP>DnBP
>>DEP >DMP >BBP >DnOP. The total concentration of six PAEs (?6PAEs) ranged from
0.87 to 250.30 mg.kg-1 with an average of 40.48 mg.kg-1, and followed the order
of parks >traffic area >mixed business and traffic area >residential area
>educational area >industrial area. The ?6PAEs presented the decreasing trend
along the main urban area - the second ring road - the third ring road. The
results of correlation analysis, principal component analysis and cluster
analysis showed that PAEs in surface dust of Xi'an City were related to the
application of plasticizers, the emission of cosmetics and personal care products
along with building materials and home decoration materials. The dose order of
human exposure to PAEs in surface dust was the direct ingestion by hand and mouth
>>dermal adsorption >inhalation via mouth and nose. Meanwhile, the intake dose of
children was higher than that of adults. However, the intake dose of DnBP, DEHP,
DBP and BBP was lower than the tolerable daily intake (TDI) suggested by European
Union Scientific Committee for Toxicity, Ecotoxicity and the Environment (EU
CSTEE) and the reference doses (RfD) proposed by U.S. EPA.
PMID- 29964407
TI - [Mercury Emission Characteristics and Mercury Concentrations of Municipal Solid
Waste in Waste Incineration Plants].
AB - Municipal solid waste (MSW) incineration is one of the most important atmospheric
mercury emission sources. To investigate the mercury concentrations of MSW and
mercury emission characteristics in incineration plants, this study analyzed the
MSW sampled in 3 typical MSW incineration plants in Shanghai, Guangzhou and Wuhu
respectively. The exhaust gas samples in incineration plants were sampled by
using OH (Ontario Hydro) method. The mercury concentrations in fly ash, and
bottom ash samples were also analyzed. The results indicated that mercury
concentrations of MSW in Shanghai, Guangzhou, and Wuhu incineration plants were
(0.39+/-0.04) mg.kg-1, (0.57+/-0.05) mg.kg-1, and (0.27+/-0.08) mg.kg-1
respectively. The mercury concentrations of exhaust gas in Guangzhou, Wuhu MSW
incineration plants were (9.5+/-3.9) MUg.m-3 and (24.1+/-6.0) MUg.m-3
respectively; Particulate mercury (Hgp), gaseous oxidized mercury (Hg2+), and
gaseous elemental mercury (Hg0) represented (0.9+/-0.8)%, (89.0+/-5.4)%, (10.1+/
4.6)% in Guangzhou MSW incineration plant, and (1.0+/-0.8)%, (65.4+/-27.6)%,
(33.6+/-27.5)% in Wuhu MSW incineration plant, respectively. Gaseous oxidized
mercury (Hg2+) of exhaust gas in different incineration process showed different
distribution proportions. Besides, mercury removal efficiency of Guangzhou, Wuhu
MWS incineration plants was 96.7% and 33.7%, respectively. The atmospheric
mercury emission factors of Shanghai, Guangzhou, and Wuhu MSW incineration plants
were (0.156+/-0.016) mg.kg-1, (0.019+/-0.002) mg.kg-1, (0.178+/-0.027) mg.kg-1
respectively. Compared with MSW incineration plants in Japan and Korea, the
atmospheric mercury emission factor of Guangzhou incineration plant was slightly
lower; Atmospheric mercury emission factors of Shanghai and Wuhu MSW incineration
plants were close to those of domestic fractional MSW incineration plants.
PMID- 29964409
TI - [Impact of Urbanization on the Sources of Dissolved n-alkane in Underground
River].
AB - To investigate the influence of urbanization on the component features of
dissolved n-alkanes (D-ALK) in the underground river in the dry season, water
samples were collected respectively at the outlet of the two underground rivers.
Components of D-ALK in these samples were quantitatively analyzed by gas
chromatography-mass spectrometry (GC-MS). The results showed that the
distribution of D-ALK carbon number at the two sites ranged from nC14 to nC35 in
dry season. The total concentration of D-ALK (DT-ALK) in Jiangjia spring ranged
from 102 to 356 ng.L-1, with an average of 230 ng.L-1. The low-number carbons
were predominant in December 2014, January and April 2015. The ratios of LMH/HMH
(nC21-/nC22+) ranged from 2.0 to 10. The carbon preference index (CPI) between
nC14 and nC25 ranged from 0.19 to 0.57, with a maximum of C16 (Cmax16). However,
in November 2014, February and March 2015, these samples had a bimodal
distribution in n-alkane. All of the CPI14-25 and the ratios of LMH/HMH were less
than 1. The CPI24-35 ranged from 1.2 to 23 with the Cmax 31 or Cmax33. During the
three months, the values of Paq were 0.2, 0.7 and 0.1, respectively. The alkane
indexes (AI) in November 2014 and March 2015 were 0.95 and 0.98, respectively.
The values of DT-ALK in Laolongdong ranged from 110 to 697 ng.L-1 with an average
of 310 ng.L-1. The carbon number distribution of each month had a low
predominance, and the CPI14-25 was less than 1. In the dry season, under the
influence of different human activities, the content and component of D-AKL in
Laolongdong which originated mainly from microorganisms was more stable than that
in Jiangjia spring, which was mainly derived from microorganisms and a mixture of
microorganisms and plants.
PMID- 29964408
TI - [Role of Sulfate-Reducing Bacteria in Mercury Methylation in Soil of the Water
Level-Fluctuating Zone of the Three Gorges Reservoir Area].
AB - Soil simulation experiments with or without addition of external mercury and a
non-indigenous bacterium were conducted under laboratory conditions, in order to
investigate whether sulfate-reducing bacteria (SRB) are the dominant mercury
methylators in the water level fluctuation zone (WLFZ) of the Three Gorges
Reservoir, which is a typical periodical wet and dry alternating environment,
locating in the Shibaozai Xinzhen Village, Zhong County, Chongqing, China (E108
degrees 12'3" and N30 degrees 24'36"). The original soil from the WLFZ was
firstly sterilized and then inoculated with or without Desulfovibrio africanus
(D. africanus DSM-2603, commercially purchased from the Culture Preservation
Center of Microorganisms in Germany, DSMZ) as the control (Test A). The
sterilized soils were respectively mixed with 0, 1, or 5 mg.kg-1 Hg2+ soil under
submerged and non-submerged conditions to simulate changes in the concentrations
of total mercury, methylmercury and the growth of D. africanus, and the effects
of environmental factor on such changes. The results showed that under the
submerged situation the release of total mercury (THg) from soils (Test B)
increased with the increase of external Hg2+ addition, and the higher the
external Hg2+, the quicker the Hg2+ release was. Meanwhile, D. africanusdisplayed
an ecological adaptability to mercury and its colony numbers were significantly
correlated with the MeHg concentrations in the soil. In soil with 5 mg.kg-1 of
external Hg2+, the total number of D. africanus reached the highest (3.65*104
cfu.g-1) while the highest MeHg concentration was 7.60*104 ng.kg-1. However, on
the one hand, the averaged numbers of soil SRB in the test B was only 193 cfu.g
1. On the other hand, in soil with 5 mg.kg-1of external Hg2+, the MeHg
concentration was as low as 5.54*103 ng.kg-1, while no significant relationships
were observed between SRB and MeHg. As a result, our results indicated that SRB
was not a predominant mercury methylator, while other bacterial groups, either
aerobic or anaerobic bacteria, might play an important role in mercury
methylation in the WLFZ of the Three Gorges Reservoir, China.
PMID- 29964410
TI - [Source Apportionment and Ecological Risk Assessment of Polycyclic Aromatic
Hydrocarbons in Surface Water from Yangtze River, China: Based on PMF Model].
AB - To study the features and ecological risk of PAHs in surface water from Yangtze
River, 19 water samples were collected from the main stream and branch of Yangtze
River in August 2015. Solid phase extraction method was used to extract PAHs, and
the concentrations of the 16 priority PAHs were determined using GC-MS. The
results indicated that the concentration of total PAHs (?PAHs) in the surface
water ranged from 17.7-110 ng.L-1 with an average value of 42.6 ng.L-1. The
predominant PAHs in the water were PAHs with 2-3 rings, accounting for 67.7% of
?PAHs. The results of molecular diagnostic ratios indicated that the origin of
PAHs was mostly combustion sources, including fossil fuel and biomass combustion.
PMF model was used to quantitatively acquire the source contribution of PAHs,
which indicated that four sources were identified and their contribution rates
were respectively biomass and coal combustion (40.1%), petroleum source (19.6%),
traffic source (17.5%) and coke oven source (22.8%). The results of ecological
risk assessment indicated that PAHs with 2-3 rings had a relatively high risk
level, and Wujiang station and lower reach had a relatively high risk level based
on risk quotient. Overall, the ecological risk of PAHs in the Yangtze River was
at a relatively low level.
PMID- 29964411
TI - [Hydro-chemical Characteristics and Quality Assessment of Surface Water in Gongga
Mountain Region].
AB - The concentrations of major ions (K+, Na+, Ca2+, Mg2+, CO32-, HCO3-, Cl-, and
SO42-), heavy metals (Cu, Cd, Pb, and Zn), and nutrient elements (N and P) in
surface water collected from Gongga Mountain region were analyzed to decipher
their spatial distribution and assess the water quality. The descriptive
statistics, Gibbs Figure, and triangular diagrams of anions and cations were
employed, and single factor evaluation was conducted. The results showed that the
average value of total dissolved solid (TDS) in Gongga Mountain region was 103.22
mg.L-1 indicating low salinity, and the hydro-chemical type was HCO3-Ca. For
whole catchment, the major ion chemistry of river water was controlled by
carbonate weathering, while the effect of atmospheric deposition was high in the
eastern area. The overall concentrations of heavy metals and nutrient elements
were low, and the eastern area had significantly higher concentrations than the
west. The quality of surface water was good from the whole point of view, while
that in the west was better than the east. It indicated that the spatial
distribution was mainly controlled by natural factors, but the water of southeast
slope had been affected by humans.
PMID- 29964412
TI - [UV-Visible Spectra Properties of DOM from Taizi River in Benxi City Section by
Multivariable Analysis].
AB - This study investigated the ability of ultra violet-visible (UV-Visible)
spectroscopy to analyze the origin,compositions,structure and humification level
of dissolved organic matter(DOM). Seven surface water samples were collected from
the Benxi City section of mainstream in Taizi River. Nine indices (SUVA254,
E2/E3, E2/E4, E4/E6, S275-295, S350-400, A2/A1, A3/A1 and A3/A2), deduced from
elemental analysis and UV visible spectroscopy of DOM, were used to assess the
humification degree. The results showed that the characteristics of DOM were
distributed along urban river and industrial wastewater discharge, and the DOM of
waste water from Benxi steel plant contained a low degree of condensation of
small organic molecules. E2/E3 showed positive correlation with E2/E4, and
negative correlations with S275-295, S350-400, A2/A1,indicating that humification
degree of DOM was not only concerned with the degree of condensation of organic
molecules, but also closely associated with the ratio between humic acid and
fulvic acid. Composition structure of DOM showed significant positive
correlations with A2/A1, SUVA254 and S275-295, and significant negative
correlations with E2/E3 and E2/E4. Based on the loadings of DOM component and
scores plot of sampling sites in Taizi River (Benxi City section),the
characteristics of DOM were distinctly distributed along urban river and
industrial wastewater discharge, proving that the river was deeply influenced by
human activity.
PMID- 29964413
TI - [Vertical Distribution Characteristics of Dissolved Organic Matter in Groundwater
and Its Cause].
AB - Dissolved organic matter (DOM) can change the species, migration and
transformation of foreign pollutants in groundwater, and the investigations of
its composition and distribution characteristics play a role in environment
protection. The groundwater DOMs were obtained at the depths of 1.2, 1.5 and 1.8
m, and its origin, composition, concentration, distribution characteristics and
influencing factors were studied using UV-Vis and fluorescence spectra combined
with parallel factor analysis and principle components analysis. The results
showed that, DOM in the groundwater originated from both terrigenous input and
microbial activities, and was comprised of humic-like matter, heterogeneous
component, and protein-like matter. Humic-like matter and heterogeneous
components showed a high concentration at 1.5 m and a low one at 1.2 m, whereas
the protein-like matter exhibited a low concentration at 1.5 m and a high one at
1.2 m. The groundwater DOM at 1.5 m exhibited the highest aromaticity,
humification, molecular weight and polar functional group content, while that at
1.2 m depth showed the lowest aromaticity, humification, molecular weight and
polar functional group content. The vertical distribution of DOM in groundwater
was related to aromaticity, humification, molecular weight and polar functional
group, and the DOM with high aromaticity, humification, molecular weight and
polar functional group resisted to biodegradation, and could easily enter into
the bottom layer groundwater.
PMID- 29964414
TI - [Sediment Characteristics of Sewer in Different Functional Areas of Kunming].
AB - The problem of sediment deposition in urban sewer network in different levels,
will not only reduce the sewer flow ability, but also release pollutants and
generate secondary pollution. The impact of secondary pollution is more serious
in the study area, Kunming, because of the combined sewer overflow in rainy
season. In order to obtain the characteristics of the sewer sediments in Kunming,
the sewer sediments from residential area, service area, cultural district, and
business district were investigated and collected. The particle size, density,
organic matter (VSS/TSS) and pollutant content of the sediments were analyzed in
this study. The results showed that there were different characteristics for the
sediments from different areas. The size of the sediments exhibited business
district >cultural district >residential area >service area, and the D50 was
concentrated in the 20 to 100 MUm except the business district. As for VSS/TSS,
the order was residential area >cultural district >business district >service
area. It was negatively correlated with the dry density with the correlation
index of R2=0.9827 and positively correlated with the water content. The contents
of sediments showed significant differences in different functional areas. The
size of COD presented residential area >cultural district >service area >business
district, and the size of TN followed residential area >cultural district
>business district >service area. As for TP, it exhibited residential area
>service area >cultural district >business district. The COD, TN and TP were
proportional to the population density of the area and TP was greatly influenced
by sediment particle size. From the branch into the Sub-main sewer, COD and TN
were irregular, and TP decreased slightly. TP mainly existed as particulate and
was more likely to deposit onto the small particle. As for TN, there was no
obvious rule about its distribution in different particle size sections. The
pollution load was generally on the high side in Kunming. The content of heavy
metals in business district was the highest among all functional areas, and the
concentrations of Cu, Zn, Pb, Cd were 284.6, 786.4, 201.2, 2.54 mg.kg-1
respectively. The average contents of Cu, Zn, Pb, Cd in urban area were 2.2, 4.4,
2.5, 8.6 times than the background values. It is suggested to control Cd and Zn
with priority.
PMID- 29964415
TI - [Concentration of Phosphorus in Sediments Interstitial Water as Affected by
Distribution of Aquatic Plants in Dianchi Lake].
AB - In order to reveal the effect of aquatic plants distribution on the mass
concentration of phosphorus in sediment interstitial water, the mass
concentrations of Dissolved Total Phosphorus (DTP), Soluble Reactive Phosphorus
(SRP) and Dissolved Organic Phosphorus (DOP) in the sediment interstitial water
and overlying water from areas with or without plants in the same site of Dianchi
were studied. The vertical variation characteristics of phosphorus forms in
sediment interstitial water were analyzed to explore the effect of aquatic plants
on the phosphorus forms in sediment interstitial water. The results showed:
1Aquatic plants had an significant effect on the phosphorus mass concentration of
the sediment interstitial water in different Dianchi lakes. However, they varied
with different distribution sites and depth. 2Aquatic plants significantly
decreased the percentage of DOP contribution in the sediment interstitial water.
The average contribution of DOP with aquatic plants was 32.87%, while that
without plants reached 57.68%; 3Aquatic plants significantly inhibited the
release of inorganic phosphorus in sediments and promoted the transformation of
DOP. The SRP diffusion flux at sediment-water interface with aquatic plants was
increased by 39.99% as compared with that without plants; 4The growth of aquatic
plants significantly reduced the concentration of phosphorus in sediment
interstitial water, especially DOP, and the reduction rate of the sediment
interstitial water DOP was from 38.02% to 85.49%. Therefore, the analysis of the
contribution and reduction rate of aquatic plants on the sediment interstitial
water DOP was of great importance in understanding the relationship between
aquatic plants and DOP, as well as the mineralization of organic phosphorus in
sediments.
PMID- 29964416
TI - [Efficiency and Mechanism of Capping with Purple Parent Rocks to Control
Phosphorus Release from Sediments].
AB - In order to study the efficiency and mechanism of capping with purple parent
rocks to control phosphorus release from sediments, three kinds of purple parent
rocks (Fei-xian-guan Formation, Peng-lai-zhen Formation and Sui-ning Formation)
which distribute widely in Chongqing, and two types of rock (limestone and
calcite) which have been found to effectively control the release of phosphorus
from sediments, were selected as active covering materials to cap the sediments
to conduct simulation experiment. The results indicated that: all three kinds of
purple parent rocks showed strong inhibition of total phosphorus release from
sediments to the overlying water, far better than limestone and calcite (P<0.05),
and the highest removal rate of total phosphorus was 94.4% in the disposal of Fei
xian-guan Formation. Those five kinds of covering materials could promote the
release and transformation of total phosphorus in sediments, which could
significantly promote the in situ conversion of OP to Ca-P, while the three kinds
of purple parent rocks were more conducive to convert the released phosphorus
into inorganic phosphorus and organic phosphorus. At the same time, those five
kinds of covering materials could also change the microbial community structure
in sediments and overlying water, and the numbers of bacteria (labeled as
PLFA16:0) were significantly negatively correlated with the content of total
phosphorus in the overlying water.
PMID- 29964417
TI - [Temporal and Spatial Distribution of Phosphorus in Paddy Fields Under Cyclic
Irrigation of Drainage Water].
AB - Considering the potential of cyclic irrigation to increase rainfall use
efficiency and reduce agricultural non-point pollution, the experiment of
phosphorus transport in paddy fields under cyclic irrigation of drainage water
was conducted to address the problem of phosphorus loss pollution and the
mismatch between rainfall temporal distribution and crop requirement in the south
of China. Lotus pond water and fishpond water were used to irrigate paddy fields
for monitoring concentrations of total phosphorus (TP), dissolved phosphorus
(DP), and dissolved reactive phosphorus (DRP) in surface water and leachate, and
soil profile total phosphorus and Olsen-P concentrations. The results showed that
the concentrations of TP, DP and DRP in surface water and leachate decreased
along the field under cyclic irrigation of drainage water, especially the
phosphorus concentrations of leachate dropped more obviously. As the phosphorus
content of cyclic irrigation water sources varied within a certain range,
phosphorus concentrations of surface water and leachate did not increased. The
concentrations of TP, DP and DRP in surface water and leachate varied with cyclic
irrigation time, and the least phosphorus concentrations were observed in August.
Top soil Olsen-P concentration decreased along the field and increased with
phosphorus content of cyclic irrigation water sources, and soil profile TP
concentration was not influenced by cyclic irrigation. Phosphorus removal ratio
of paddy field could be increased by extending field length or cyclic irrigation
in August.
PMID- 29964418
TI - [GO/QPEI Nanocomposite for Fast and High-capacity Removal of M. Aeruginosa].
AB - This work described the synthesis of graphene oxide/quanternary ammonium
polyethylenimine (GO/QPEI) nanocomposite as a novel and highly efficient
Microcystis aeruginosa (M. aeruginosa) removal material. From pH 4 to 10, the
removal efficiency of M. aeruginosa by GO/QPEI in 2 min was over 96%. The
adsorption isotherm fitted the Freundlich model better and the maximum capacity
of GO/QPEI was 5.58*1011 cells.mg-1. The kinetic data supported a pseudo-second
order adsorption behavior for GO/QPEI. The enhanced removal of M. aeruginosa
could be attributed to the synergistic effect of GO nanosheet and the grafted
QPEI.
PMID- 29964419
TI - [Enhanced Pollutant Removal Performance of an Integrated Biological Settling Tank
from Micro-polluted Water Bodies].
AB - To improve the capacity of present drinking water purification process on the
removal of soluble pollutants and solve the problem of large area requirement and
single function existing in the application of horizontal sedimentation tank, a
novel biological settling tank was developed based on the designing concepts of
rotating biological disk and sedimentation tank. Experimental results showed that
the usage of rotating biological disk did not have notable effects on the
turbidity removal capacity of the horizontal sedimentation tank. When the organic
loading rate was 0.46 g.(m2.d)-1, the removal rates of organic pollutants, NH4+
N, TN, and TP were determined to be 81.4%, 95.0%, 21.1% and 86.0%, respectively.
Further study showed that denitrification and dephosphorization processes
competed for the limited carbon source existing in the water phase. With the
increase of organic loading rate in the raw water, the removal rate of TP was
improved. Meanwhile, the concentrations of organic matters and NH4+-N in the
settled water were not affected, which indicated that the biological settling
tank showed a capacity in resisting organic loading rate shock and could be used
in the enhanced pollutant removal in treating micro-polluted water.
PMID- 29964420
TI - [Odorants Removal and Microbial Characteristics in Treatment of Micro-polluted
Source Water with Biological Powdered Activated Carbon-Ultrafiltration Combined
Process].
AB - The odorants in simulated micro-polluted source water were removed by the
Biological Powdered Activated Carbon-Ultrafiltration (BPAC-UF) combined process,
and variations of microorganisms in the combined process were discussed. Compared
with the conventional process of coagulation and sedimentation, BPAC-UF combined
process had better performance in controlling odorants in micro-polluted source
water. The average removal rates of dimethyl trisulfide, 2-methylisoborneol and
beta-ionone reached up to 77.51%, 65.86% and 98.43%, respectively. The process
was more adaptable to raw water shock load. The carbon tank which had much more
microbial biomass than other areas was determined to be the main unit for
removing odorants. The biomass changed smoothly in the carbon tank, while the
removal of odorants in raw water was stable in the process.
PMID- 29964421
TI - [Effect of Polysilicic Acid on the Deposition Behavior of Different Aluminum
Species].
AB - To understand the water quality problems caused by deposition and re-dissolution
behaviors of residual aluminum in drinking water distribution system (DWDS), the
effect of polysilicic acid on the deposition and re-dissolution behaviors of
different aluminum species was investigated by using jar tests and quartz crystal
microbalance, which could demonstrate the deposition behavior of different
aluminum species and the physic-chemical properties of deposited layers. The
results showed that the effect of polysilicic acid on the deposition behavior of
different aluminum species was significant. Al0 (mainly monomeric species), Al13
and Al30 (polymeric species) could react rapidly with polysilicic acid, and some
insoluble products formed. However, the stability of insoluble products from
different aluminum species was distinct. The insoluble product formed by reaction
of Al0 with polysilicic was relatively stable. With regard to the systems of
polysilicic acid with Al13 and Al30, the dissolved aluminum concentration
increased with reaction time, which indicated that the deposited product could be
gradually transformed to soluble monomeric or oligomeric aluminum species.
Compared with the influence of Al/Si ratio on Al0, the ratio of aluminum to
silicon significantly affected the deposition and re-dissolution behavior of Al13
and Al30, and the re-dissolution rate of insoluble aluminum was the most rapid
when the ratio of aluminum with silica was 0.2:20 (as mass ratio of Al to SiO2).
PMID- 29964423
TI - [Degradation of the Nitrogenous Heterocyclic Compound Quinoline by O3/UV].
AB - The influences of various factors including initial concentration of quionline
solution, static duration after reaction, initial pH, HCO3-on the degradation of
quinoline by O3/UV were analyzed in this study. In addition, the degradation
mechanism and pathways were also analyzed. The results showed that reaction rate
constants and removal rate of quinoline decreased with the increase of the
initial concentration of quinoline. The best degradation efficiency of quinoline
was achieved under the alkaline conditions (pH 7-9). Removal rate of quinoline
was obviously influenced by HCO3-, and was reduced by 42.01% within 6 min when
the concentration of HCO3- was 100 mg.L-1. There was neglected effect of static
duration after reaction on the removal rate and mineralization rate of quinolone.
The intermediate products of quinoline were mainly 8-hydroxyquinoline, 5
hydroxyquinoline, 2(1H)-quinoline ketone, 2-pyridinecarboxaldehyde and so on. The
main degradation pathways of quinoline in the O3/UV system were addition
reaction, substitution reaction and electrophilic substitution mediated by O3
and.OH.
PMID- 29964422
TI - [Concentration Variation and Removal of Amino Acids in Typical Drinking Sources
in the South of China].
AB - Amino acids are the main components of nitrogenous organic matter in surface
water. In order to reveal the concentration variation and removal of amino acids
in reservoirs water, the concentration variation of the twenty common amino acids
for three main reservoirs' water in a typical southern city of China was
monitored between May and October in the year of 2015 by HPLC, and the space
distribution and change trend of the twenty amino acids were analyzed. In
addition, the removal of the twenty amino acids was also studied by different
water treatment processes. The results showed that the amino acids contents and
composition were different among the three reservoirs. Aspartic acid, cysteine
and leucine were the main amino acids for the three reservoirs. Besides, there
was no obvious seasonal variation of amino acids content for reservoir C.
However, the concentration of amino acids in autumn was higher than that in
summer. Coagulation and sedimentation were main units for the removal of amino
acids in conventional and BAC-UF processes while O3 oxidation was the main unit
in O3-BAC process. 94.42%, 66.04% and 49.75% of total amino acids contents were
removed by the conventional, BAC-UF and O3-BAC processes, respectively.
PMID- 29964424
TI - [Impact of Anthraquinone-2-sulfonic Acid on the MO Decolorization, Hydrogen
Production and Energy Creation During Anaerobic Fermentation of Klebsiella
oxytocaGS-4-08 with Sucrose].
AB - The effect of 0-0.5 mmol.L-1 anthraquinone-2-sulfonic acid on anaerobic
fermentation of Klebsiella oxytocaGS-4-08 was analyzed. By comparing bio-hydrogen
production, carbon source degradation, and degradation products, the optimal
concentration of 0.1 mmol.L-1 was acquired. Under this concentration, Klebsiella
oxytocaGS-4-08 could decolorize 100% methyl orange within 10 h, degrade 92%
sucrose within 25 h, meanwhile produce 0.117 mol.mol-1 ethanol, 0.116 mol.mol-1
acetic acid, 2.25 mol.mol-1 hydrogen. Besides, the promoting mechanism of AQS on
MO decolorization and hydrogen production by Klebsiella oxytocaGS-4-08 was
analyzed by comparing the experimental results and the literatures. The electron
transfer and energy conversion are analyzed during the bacterial degradation
process by converting the substances into COD; the optimal electron yield was
87.98% and the optimal energy generation rate was 802 kJ.mol-1, and both were
achieved under 0.1 mmol.L-1 of AQS. Using Klebsiella oxytoca GS-4-08, at least
two types of biofuels could be produced via fermentation process, which showed
prospects in future applications.
PMID- 29964425
TI - [Classification and Analysis of Dissolved Organic Matter in 2-Buternal
Manufacture Wastewater].
AB - The dissolved organic matters from 2-buternal manufacture wastewater were
fractionated into seven fractions by ultra-filtration membrane separation. The
amounts and structural compositions of organic compounds in different molecular
weight ranges were characterized by dissolved organic carbon (DOC), ultraviolet
spectrum (UV), Fourier transform infrared spectrometer (FT-IR) and gas
chromatography with mass spectrometry (GC-MS). The results showed that the
fraction of molecular weight less than 1*103 had the largest proportion in the
wastewater, and occupied 88.57% of the DOC. There were 27 kinds of compounds
qualitatively analyzed by GC-MS, mainly including aldehyde, ketone, ester,
alcohol, phenol, organic acid, alkane and other heterocyclic compounds. The
proportions of compounds of peak area accounting for total peak area of organic
matters were 6.9%, 5.3%, 35.4%, 13.2%, 4.6%, 0.4%, 1.7% and 16.8% respectively,
adding up to 84%. The analysis of UV and FT-IR demonstrated that the spectral
absorptive characteristics of organic compounds from different fractions were not
significantly different. The fractions contained carbonyls, hydroxys and aromatic
compounds, which was consistent with the qualitative analysis of GC-MS. The
results of this study provide an important guidance for the development and
optimization of 2-buternal manufacture wastewater treatment process.
PMID- 29964426
TI - [Concentration of Nitrate in Main Anoxic Stage and PHA, TP Metabolism for
Nitrogen and Phosphorus Removal in Single Sludge System with Continuous Flow].
AB - Based on test results and mass balance, PHA, TP metabolic regularity was revealed
under different nitrate nitrogen concentrations in main anoxic stage [c(NO3)] for
nitrogen and phosphorus removal in single sludge system with continuous flow,
then the effectiveness of using c(NO3) as control parameter was proved from the
perspective of the reaction mechanism. During experiment period, the influent
COD, total nitrogen (TN), and total phosphorus (TP) concentrations were
stabilized at (285.78+/-18.19), (58.13+/-3.79), and(7.14+/-0.51) mg.L-1,
respectively. The experiment was carried out under the condition that the c(NO3)
values were 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 mg.L-1 based on the
feedback control structure using PLC automatic control system to control the
nitrifying liquid flow with the water quality. The sludge load of COD was
(0.253+/-0.071)kg.(kg.d)-1, the sludge load of TP in anaerobic stage was (0.006+/
0.001) kg.(kg.d)-1, the sludge load of TN in aerobic stage was (0.049+/-0.006)
kg.(kg.d)-1, the hydraulic retention time (HRT) in bioreactor was 9h, the sludge
recycle flow was 0.5, and the mixed liquor recycle was 1.0. The results showed
that effect of c(NO3) value on PHA synthesis and storage rate in the ANS was
conspicuous, and the percentage of PHA storage occupied 74% of COD removal when
c(NO3) value was 2.5 mg.L-1.The impact of c(NO3) value on PHA degraded in the
main anoxic stage was great, and the percentage of PHA degradation in the main
anoxic stage occupied 55% of total PHA degradation when c(NO3) value was 2.5 mg.L
1. The phosphorus released in anaerobic stage changed along with increasing
c(NO3), and the amount of phosphorus released obtained the maximum value 6.16 g.d
1 when c(NO3) value was 2.5 mg.L-1. In addition, under c(NO3) value of 2.5 mg.L
1, the amount of total phosphorus uptake and anoxic phosphorus uptake obtained
the maximum values of 8.04 g.d-1 and 3.67 g.d-1, respectively. Then it was
confirmed thatc(NO3) could serve as a run controlling parameter with the best
value of 2.5 mg.L-1 from the perspective of PHA and TP metabolic mechanism.
PMID- 29964427
TI - [Distribution Characteristics of Anaerobic Ammonia Oxidation Bacteria in
Sediments from the Adjacent Seas of Yangtze Estuary].
AB - Marine nitrogen cycle is of great significance to maintain the marine ecological
balance. Anaerobic ammonia oxidation (ANAMMOX) process driven by anaerobic
ammonia-oxidizing bacteria is an important way of promoting the marine nitrogen
removal. In this study, quantitative PCR (qPCR), combining with environmental
factors analysis, were used to study the distribution of ANAMMOX bacteria in the
sediments from Yangtze River Estuary and its adjacent waters in summer, 2011. The
results showed that the spatial abundance distribution of ANAMMOX bacteria was
closely related to environmental factors. Total organic carbon, salinity, and
concentration of ammonium played vital roles in regulating ANAMMOX bacteria
abundances in this area. The abundance distribution of ANAMMOX bacteria was
significantly positively correlated with total organic carbon content
(P<0.01,r=0.69), reducing along with the increasing concentration of nitrite and
DO, while the influence from salinity was complicated.
PMID- 29964428
TI - [Bacterial Community Composition of Activated Sludge from Coking Wastewater].
AB - Coking wastewater is a kind of highly toxic and refractory organic wastewater,
and aerobic activated sludge, which is dominated by bacteria, determines the
efficiency of coking wastewater treatment. However, the bacterial community
structure of activated sludge from coking wastewater has rarely been reported.
454 sequencing technology was applied to investigate the structure and
biodiversity of the bacterial community. The results of thermal cluster analysis
and principal component analysis demonstrated the differences in biodiversities
of different activated sludge bacterial communities. The bacterial communities
were mainly composed of Proteobacteria, Planctomycetes, Acidobacteria, Candidatus
Saccharibacteria, Bacteroidetes, Cyanobacteria, Actinobacteria, Chloroflexi,
Firmicutes, Thaumarchaeota, Ignavibacteriae, Verrucomicrobia and Unclassified
bacteria. Proteobacteria was the dominant phylum and its abundance was 36.00%
76.98%. The primary genera were Thiobacillus, Thauera, Comamonas, Caldimonas,
Steroidobacter, Nitrosomonas, Phycisphaera and Gp4. Most of these genera were
related with aromatic hydrocarbon degradation, nitrification and denitrification
processes. These results provide a theoretical basis for removal mechanism of
pollutants in coking wastewater.
PMID- 29964429
TI - [Soil Bacterial Communities Under Different Vegetation Types in the Loess
Plateau].
AB - In this study, we collected soil samples from four different arborcommunities and
four herb communities, which represented two vegetation ecosystems in the
northwest of the Loess Plateau. Our objectives were to determine the diversity of
soil bacterial communities and the affecting factors with the method of 454 high
throughput pyrosequencing technology. The results showed that the structures of
the microbial communities differed in terms of both the predominant phylum and
the relative abundance of each phylum. At the phylum level, the dominant phyla
were Proteobacteria, Actinobacteria, Acidobacteria, Chloroflexi and
Planctomycetes. At the class level, Actinobacteria, alpha-Proteobacteria,
Acidobacteria, beta-Proteobacteria and Planctomycetacia were predominant. The
relative abundance of Actinobacteria in grass vegetation ecosystem was more
abundant than that in forest vegetation ecosystem. Proteobacteria in forest
vegetation ecosystem were more abundant. Soil pH was significantly correlated
with the relative abundance of Actinobacteria. Soil organic matter,soil total N
and soil total P were the key factors affecting soil Proteobacteria. These
results will provide useful information for the diversity of soil bacteria and
guide the practice of vegetation restoration in the Loess Plateau.
PMID- 29964430
TI - [Effects of Phenol on Activity and Microfauna Community Structure of Activated
Sludge].
AB - In order to investigate the effects of phenol on activity and microfauna
community structure of activated sludge, phenol with different concentrations
were added into the wastewater for activated sludge culturing in a SBR reactor,
then the activity parameters of TTC-ETS and INT-ETS of activated sludge were
measured, and the dynamics of microfauna community was analyzed. The results
indicated that TTC-ETS activity was more applicable to evaluate the effects of
phenol on sludge activity than INT-ETS activity. The higher the concentration of
phenol was, the more seriously the sludge activity was inhibited. When 50 mg.L-1
of phenol was added into the influent, the inhibition rate of sludge activity was
(20.75+/-10.43)%, while it increased to (39.73+/-26.92)% with a great fluctuation
at the phenol concentration of 100 mg.L-1. The inhibition rate of sludge activity
fluctuated at about 40% in the later period of sludge culturing with 300 mg.L-1
of phenol. The inhibitory effects on microfauna community in activated sludge
increased with increasing phenol concentration. Phenol had different effects on
various groups of microfauna community, i.e., only one group (testate amoebae)
was inhibited significantly at a low feeding concentration of phenol, many groups
(sessile ciliates, testate amoebae, crawling ciliates, carnivorous ciliates) were
inhibited at the phenol concentrations of 100 mg.L-1 and 300 mg.L-1, whereas a
few groups (flagellates, nematodes, etc.) were promoted at the phenol
concentration of 300 mg.L-1. There was a certain degree of relationship between
sludge activity and microfauna under the influence of phenol, which means that
Centropyxis aculeata, Plagiocampa mutabilis etc., may be bio-indicators for low
sludge activity, and Epistylis lacustris, Bodo lens and Pleuromonas jaculans can
be used as bio-indicators for high sludge activity in the activated sludge used
to treat phenolic wastewater.
PMID- 29964431
TI - [Comparative Investigation of Antibotic Resistance Genes Between Wastewater and
Landfill Leachate].
AB - The increasing output of wastewater and landfill leachate during the rapid
urbanization exacerbated the human health risks induced by antibiotic resistance
genes(ARGs). For further insight into antibiotic resistance genes(ARGs) of
wastewater (adding leachate before treatment) and landfill leachate, high
throughput qPCR technique was used to investigate their abundance and
diversities. A total of 187 unique ARGs were detected in wastewater, which was
significantly higher than that in leachate (39 unique ARGs were
detected)(P<0.05). A total of 119 antibiotic resistance genes were significantly
enriched in wastewater compared with the landfill leachate (P<0.05), especially
the tnpA-04 and blaVEB, which belongs to mobile gene elements(MGEs) and beta
Lactamase, increased by 3338-fold and 1061-fold, respectively. Our results showed
that the profile of ARGs was significantly different between the wastewater and
leachate, and the wastewater was the important reservoir of ARGs.
PMID- 29964432
TI - [Performance and Influencing Factors of Dissimilatory Nitrate Reduction to
Ammonium Process by the Strain Desulfovibrio sp. CMX].
AB - The process of dissimilatory nitrate reduction to ammonium (DNRA) plays an
important role in the presence and conversion of ammonium ions in nature.
However, the influencing factors and mechanisms of DNRA process in sulfate
reducing bacteria (SRB) have not yet been identified. The ability, influencing
factors and mechanisms of DNRA was investigated in Desulfovibrio sp. CMX isolated
previously in our laboratory. The results showed that the production rate of
ammonium reached 85.8% and 97.3% respectively with NO3- and NO2- (10 mmol.L-1) as
the sole electron donor and nitrogen source. Meanwhile, there was no by-products
such as N2 and N2O. Then the effects of different extra nitrogen sources and
initial concentrations of sulfate and sulfide on DNRA process were also
investigated. As a result, extra nitrogen, yeast extract, could promote DNRA
process by improving both growth and metabolism of the strain. In another study,
sulfate promoted the nitrate reduction stage while inhibited the nitrite
reduction. Overall, the DNRA process by Desulfovibrio sp. CMX was inhibited by
sulfate. In addition, both the growth and two stages of the DNRA process were
inhibited in the presence of sulfide. Dose effect of sulfide was observed.
Inhibition was enhanced with the increase of sulfide concentration. It's
noticeable that the inhibition on nitrate reduction was stronger than the
inhibition on nitrite reduction with 6 mmol.L-1 of sulfide, leading to the lower
reduction rate of nitrate than that of nitrite. In this condition, no
accumulation of nitrite was observed in the system.
PMID- 29964433
TI - [Effect of Straw Incorporation and Domestic Sewage Irrigation on Ammonia
Volatilization from Paddy Fields].
AB - A pot experiment was conducted to study the effect of straw returning and
domestic sewage irrigation on the dynamics of NH4+-N concentration and pH in the
flood water, and ammonia volatilization of paddy fields. The results showed that
the NH4+-N concentration in flood water was significantly increased by wheat
straw returning while significantly decreased by domestic sewage irrigation. The
cumulative ammonia volatilization in the whole rice season under tap water
irrigation and straw removal treatment was 58.29 kg.hm-2, accounting for 24.29%
of the total N applied. The N loss ratio of ammonia volatilization was
significantly increased to 45.66% by wheat straw returning, while significantly
decreased to 17.26% under straw removal and 32.72% under straw returning by
domestic sewage irrigation. Significant positive interaction was observed between
straw incorporation and domestic sewage irrigation on ammonia volatilization
loss. The average N loss from ammonia volatilization during the tillering stage
was the highest among the three fertilization stages, accounting for 7.38%-24.44%
of the total N applied. In addition, ammonia volatilization fluxes showed a
significant positive correlation with the flood water NH4+-N concentration,
irrespective of the irrigation water, but had no significant correlation with pH.
These results indicated that straw returning increased ammonia volatilization
losses, whereas domestic sewage irrigation could effectively reduce ammonia
volatilization losses and simultaneously replace 44.41% of chemical nitrogen
fertilizer by the N contained in the domestic sewage. The combination of domestic
sewage irrigation and straw returning would be an ecological and environmental
friendly measure for rice nitrogen management in Taihu Lake region.
PMID- 29964434
TI - [Seasonal Effect of Simulated Nitrogen Deposition on Soil Respiration and Soil
Enzyme Activity in Masson Pine Forest in Mt. Jinyun, Chongqing, China].
AB - Soil enzymes involved in the conversion of soil carbon and nitrogen, meanwhile
the availability of soil carbon and nitrogen is the base of soil enzymes, yet
atmospheric N deposition influences the release of soil CO2 by reduce the
activities of soil enzyme. The objective of this study was to investigate the
effect of different nitrogen deposition on soil respiration and soil enzymes, and
explore the relationship among soil respiration, soil temperature, soil moisture
and soil enzymes in the Masson pine forest. The results might provide a reference
for further study on the effects of nitrogen deposition on pine forest ecosystem.
From May 2014 to July 2015, three nitrogen application treatments and a control
treatment were set up: low nitrogen [N5, 20 g.(m2.a)-1], moderate nitrogen [N10,
40 g.(m2.a)-1], high nitrogen [N15, 60 g.(m2.a)-1] and control treatment [N0, 0
g.(m2.a)-1) in the Masson pine forest. We measured soil respiration, soil
temperature, and soil moisture simultaneously by using the Automated Soil CO2
Exchange Station (ACE, UK). The results showed that: 1 Soil enzymes and soil
respiration had obvious seasonal variation, soil respiration of N0, N5, N10 and
N15 was the highest in Summer, followed by the Spring and Autumn, and the lowest
in Winter, and no consistent change rule was found in soil enzymes. 2 Generally,
nitrogen deposition suppressed soil respiration and soil enzymes, and these
inhibitory effects were strengthened with increasing levels of nitrogen
deposition. The only exception in which nitrogen deposition enhanced soil
respiration was in the Masson pine forest in Winter, In Spring, Summer and
Autumn, nitrogen deposition suppressed soil enzymes, while there was difference
among Ure, Ive, CAT and ACP in Winter. 3 stepwise regression showed that in
control treatment and low nitrogen treatment, T, Ure and Ive made great
contributions to the Rs, and Rs rapidly increased with the increase of T, Ure and
Ive. In middle nitrogen treatment, T, Ure and CAT made great contributions to the
Rs, and Rs increased with the increase of T, Ure and CAT. In high nitrogen
treatment, Rs decreased with the increase of Ure, yet Rs increased with the
increase of CAT and W.
PMID- 29964435
TI - [Effects of Biochar Amendment and Irrigation on Denitrification Losses in
Greenhouse Tomato Fields].
AB - Biochar addition and irrigation are normal farm practices for tomatoes
management, while their impacts on denitrification are less known. In this study,
three irrigation treatments(hereafter main plots)were set as 50% (W50%), 75%
(W75%) and 100% (W100%) of reference evapotranspiration (ET0), and the subplots
coupled three biochar treatments at the rates of 0 (B0), 25 t.hm-2 (B25) and 50
t.hm-2 (B50). Typical soil samples in each plot were collected when tomatoes were
harvested in 2014 and 2015. We used acetylene inhibition method to study the
denitrification loss, and also measured N2O emissions of tomato soil without
acetylene amendment. The results showed that biochar and irrigation significantly
changed the physical and chemical properties of the soil. Adding biochar improved
total carbon, total nitrogen content and pH of the soil, while reduced the
content of NH4+-N and NO3--N compared to B0. On the contrary, irrigation reduced
the amount of total nitrogen and total carbon content. As a result, both biochar
and irrigation significantly reduced denitrification losses (P<0.05). Moreover,
the interaction of biochar and irrigation significantly reduced soil inorganic
nitrogen and denitrification losses (P<0.05),and the orders of the influencing
factors of NO3--N were irrigation, biochar, their interactions in turn, the
orders of the influencing factors of NH4+-N were biochar, irrigation, their
interactions in turn, the orders of the influencing factors of denitrification
losses were irrigation, biochar, their interactions in turn. Denitrification
losses were positively related to inorganic nitrogen content in the soil,
CO2mineralization rates and N2O emission rates. The ratio of N2O/DN, ranging from
0.31% to 1.88%, was significantly affected by biochar and irrigation treatment in
the fields (P<0.05).
PMID- 29964436
TI - [Effects of Soil Texture on Autotrophic CO2 Fixation Bacterial Communities and
Their CO2 Assimilation Contents].
AB - Autotrophic bacteria can assimilate atmospheric carbon dioxide (CO2) and convert
CO2 into organic carbon. The CO2 fixation by autotrophic bacteria is important
for the improvement of carbon sequestration in agricultural soils. However, the
effect of soil texture on autotrophic CO2 fixation bacteria and their CO2
fixation capacity is still unknown. Here, two paddy soils with different textures
(loamy clay soil and sand clay loam soil) were incubated with continuous 14C-CO2
in a glass chamber. The two soils were developed from the same parent. At the end
of 110 days incubation, the 14C-CO2 incorporated in soil organic carbon (14C
SOC), microbial biomass carbon (14C-MBC) and dissolved organic carbon (14C-DOC)
were measured to explore the effects of soil texture on the autotrophic bacterial
CO2 fixation rates. The effect of soil texture on the composition and diversity
of autotrophic CO2 fixation bacterial community was investigated using cloning
and sequencing of the cbbL gene, which encodes ribulose-1,5-biphosphate
carboxylase/oxygenase (RubisCO) in the Calvin cycle. The results showed that the
average contents of 14C-SOC, 14C-MBC and 14C-DOC were 133.81, 40.16 and 8.10
mg.kg-1 in loamy clay soil, respectively, which were significantly higher than
their corresponding contents in sand clay loam soil (P<0.05). This suggested that
soil texture not only affected the amounts of autotrophic bacteria CO2 fixation
but also had an effect on the transformation of microbial assimilated 14C in
soil. The cbbL gene libraries of two soils were significantly different as
revealed by libshuff analyses (P<0.05). Phylogenetic analysis showed that cbbL
sequences from the loamy clay soil were closely affiliated with known cultures
such as Rhodoblastus acidophilus, Blastochloris viridis, Thauera humireducens,
Mehylibium sp.and Variovorax sp., whereas these sequences belonging to the sand
clay loam soil were related to branching lineages originating from Rhizobiales
and Actinomycetales.Rarefaction curve, clone library coverage and diversity index
analysis based on bacterial cbbL clone libraries indicated that the loamy clay
soil had higher cbbL gene diversity compared to the sand clay loam soil. These
results suggested that soil texture had a pronounced effect on the composition
and diversity of autotrophic CO2 fixation bacterial communities. The higher clay
content, nutrient availability and cation exchange capacity may stimulate the
growth and activity of autotrophic bacteria, and result in the higher amounts of
14C in loamy clay soil. These data broaden the understanding and knowledge of
mechanisms of microbial carbon fixation and their influencing factors in
agricultural soils.
PMID- 29964437
TI - [Simulation of the Absorption, Migration and Accumulation Process of Heavy Metal
Elements in Soil-crop System].
AB - Soil-crop system is an important way that heavy metals harm the ecological
environment and human health. To research and understand the process of heavy
metal absorption, migration and accumulation in soil-crop system is important for
the prevention and control of heavy metal pollution and the health of human
beings. In this paper, we established a model for crop uptake of heavy metals to
calculate the heavy metals contents of wheat roots, stems, leaves and grains, and
we analyzed the accumulation process of heavy metals in roots, stems, leaves and
grains in the growth cycle of wheat. The predicted values were compared with the
measured values to test the accuracy of the model. The results demonstrated that
different parts of wheat had different heavy metal absorption capacity, the
absorption of the roots was the strongest, followed by leaves, and the absorption
capacity of stems and grains was weak. In addition, the contents of different
heavy metals in each part of wheat were also significantly different. The content
of Cu was the highest, followed by Ni, while the contents of Pb and Cd were
small. In the process of wheat growth, the heavy metal accumulation rate of stem,
leaf and grain began to slow down at 90, 60 and 100 days respectively, and the
concentration of heavy metals reached the maximum gradually, while the
accumulation rate of heavy metals in roots showed a growing trend. We studied the
process of absorption, migration and accumulation of heavy metals in soil-crop
system by using numerical simulation technology, which can provide scientific
basis for preventing the ecological and health risks of heavy metal pollution.
PMID- 29964438
TI - [Synergetic Control of Bioavailability of Pb, Cd and As in the Rice Paddy System
by Combined Amendments].
AB - This paper studied the effects of applying two combined amendments LST
(limestone+meerschaum+titanium dioxide) and LSF (limestone+meerschaum+ferric
sulfate) at different ratios of 0, 1, 2, 4, 8 and 16 g.kg-1 on bioavailability
Pb, Cd and As in paddy soil and bioaccumulation in rice plants through a pot
experiment planting rice. The results indicated that: 1Compared with the control,
applying LST and LSF could both significantly increase soil pH values (P<0.05),
and LST increased the soil pH values more. 2Applying combined amendments LST and
LSF with the amount of 1-16 g.kg-1 decreased exchangeable contents of soil Pb, Cd
and As significantly by 16.8%-88.3%, 22.4%-73.7%, 2.25%-43.8%, and 20.2%-86.9%,
20.7%-51.2%, 18.0%-55.1%, respectively. LST and LSF significantly decreased
contents of Pb, Cd and As of rice root, shoot, husk and brown rice. When the
applying amount of LST and LSF was 16 g.kg-1, the contents of Pb, Cd and As in
brown rice decreased by 50.7%, 64.7%, 34.1%, and 40.7%, 40.7%, 36.2%,
respectively. 3The ability of rice organs transferring Pb and As was husk>rice
straw>root, and that transferring Cd was husk >root >rice straw. The ability to
transfer Pb, Cd and As from rice straw to brown rice was Cd >As >Pb. 4After
applying LST and LSF, a significant positive relationship was observed between
contents of Pb, Cd and As in brown rice and exchangeable contents of these
elements in soil. Between contents of Pb, Cd and As in brown rice and soil pH
values, there was a significant negative correlation.
PMID- 29964439
TI - [Effects of Different Organic Materials on Bio-availability of Cd, Pb in a
Contaminated Greenhouse Soil].
AB - A two-season soil culture experiment was continually conducted to study the
effects of three organic materials,namely Danty, Peat and Biochar,respectively,on
combined forms and bio-availability of cadmium (Cd) and lead (Pb) under Cd and Pb
in single and combined pollution during 2014-2015. This study aimed to provide a
theoretical basis for remediating greenhouse soil contaminated with heavy metals
Cd and Pb using organic materials. The main results were as follows: the content
of DTPA-Cd decreased significantly by 11.9%(P<0.05) in the soil of Cd and Pb
combined pollution with the application of danty, the total of exchangeable Cd,
carbonate-bound Cd and iron-manganese oxide bound Cd was reduced by 26.4% and
34.4% in the soil, and the accumulation of Cd in shoots was significantly cut
down by 32.0% and 28.0% (P<0.05) respectively in Cd single and Cd and Pb combined
pollution after applying danty; the content of DTPA-Pb was significantly depleted
by 83.5% and 83.8%(P<0.05), the total of exchangeable Pb, carbonate-bound Pb and
iron-manganese oxide bound Pb was decreased by 34.5% and 13.9% in the soil and
the accumulation of Pb in shoots was significantly reduced by 32.0% and 30.0%
(P<0.05) in Pb single and Cd and Pb combined pollution respectively as the use of
danty. The content of DTPA-Cd was significantly decreased by 18.9% (P<0.05) in
the soil of Cd and Pb combined pollution with the use of peat, the accumulation
of Cd in shoots was reduced by 38.0% and 23.4%(P<0.05) in Cd single and Cd-Pb
combined pollution respectively after the application of peat; The content of
DTPA-Pb was significantly decreased by 2.7% and 7.2%(P<0.05), the total of
exchangeable Pb, carbonate-bound Pb and iron-manganese oxide bound Pb was
decreased by 15.8% and 14.6% in the soil and the accumulation of Pb in shoots was
significantly reduced by 12.7% and 23.4% (P<0.05) respectively in Pb single and
Cd and Pb combined pollution due to the application of peat. The pH value of the
soil was increased by the use of biochar, the content of DTPA-Cd was reduced by
4.7% and 15.0% respectively in the soil of Cd single and Cd and Pb combined
pollution, and the accumulation of Cd in shoots was significantly minified by
38.0% and 23.4% respectively in Cd single and Cd and Pb combined pollution as the
application of biochar. The content of DTPA-Pb was decreased by 6.8% and 1.0% and
the total of exchangeable Pb, carbonate-bound Pb and iron-manganese oxide bound
Pb was cut down by 11.9% and 30.0% in the soil of Pb single and Cd and Pb
combined pollution respectively by the application of biochar. The content of Cd
in plant was most significantly positively correlated with the content of
exchangeable Cd in soil (P<0.01). The content of Pb in plant was most
significantly positively correlated with the total of exchangeable Pb, carbonate
bound Pb and iron-manganese oxide bound Pb (P<0.01). In summary, after the
application of danty, peat and biochar, the proportion of highly active content
of Cd and Pb was minified through adjusting soil pH and immobilizing Cd and Pb by
means of adsorption and complexation in greenhouse soil. With the analysis of
input-output, the application of danty, peat and biochar costs 4050 yuan.hm-2,
11250 yuan.hm-2 and 22500 yuan.hm-2, respectively. Thus danty, peat and biochar
could be used as effective organic agents in the remediation of Cd and Pb
contaminated greenhouse soil.
PMID- 29964440
TI - [Effect of Montmorillonite on Fractions and Availability of Phosphorus in Soils
Applied with Organic Fertilizer].
AB - An incubation experiment was carried out to study the effect of montmorillonite
on pH, the fractions and availability of phosphorus in a sandy yellow soil (SY)
and a mineral flavicant soil (MF) applied with biogas residues of swine manure
(BSR). The rates of montmorillonite applied were 0%, 5%, 7.5% and 10%,
respectively. The results indicated that soil pH was not affected by BSR, but was
significantly increased by montmorillonite. In both soils, application of BSR
caused an increase in the content and proportion of Al-P during the incubation,
and an increase in the content but a slight decrease in the proportion of Fe-P in
later period of incubation. The concentration of O-P was not markedly changed,
but its proportion was decreased by applying BSR in both soils. The changes of Ca
P varied with soils. BSR had no significant influence on Ca-P content, but
decreased the proportion of Ca-P in SY, meanwhile, it increased both Ca-P content
and proportion in MF. Addition of montmorillonite in soils applied with BSR
decreased the contents and proportions of Al-P and O-P, and the proportion of Fe
P did not change the contents of Fe-P, but increased the content and proportion
of Ca-P in SY. In MF, montmorillonite could decrease the contents and proportions
of Fe-P and O-P, and the proportion of Al-P did not affect the content of Al-P,
but increased the contents and proportions of Ca-P greatly. The contents of
available phosphorus (A-P) were enhanced by 17.9%-38.0% and 17.1%-33.7% in SY and
MF respectively, and the phosphorus activation coefficient (PVC) was
significantly improved in both soils by applying BSR. The contents of A-P were
reduced by 8.8%-35.5% and 1.1%-11.6% in SY and MF respectively. Correlation
analysis showed that montmorillonite reduced the availability of phosphorus
through increasing pH and contents of Ca-P, decreasing the content of Al-P in SY,
and through increasing pH and decreasing content of Fe-P in MF. The availability
of phosphorus in SY was influenced more obviously than that in MF by
montmorillonite.
PMID- 29964441
TI - [Effect of Nano Zeolite on Chemical Fractions of Cd in Soil and Uptake by Chinese
Cabbage at Different Soil pH and Cadmium Levels].
AB - Incubation experiments were carried out to investigate the influence of different
nano zeolite(NZ) and ordinary zeolite(OZ) levels(0, 5, 10 and 20 g.kg-1) on the
fraction distribution coefficient (FDC) of Cd and soil CEC at different soil pH
(4, 5, 6, 7 and 8) when exposed to different cadmium(Cd) levels(1, 5, 10 and 15
mg.kg-1), and pot experiment were carried out to investigate the effects of nano
zeolite(NZ) and ordinary zeolite(OZ) on the growth, Cd concentration and Cd
accumulation of Chinese cabbage. The results showed that nano zeolite and
ordinary zeolite decreased the concentration and FDC of exchangeable Cd (EX-F),
and increased the concentration and FDC of carbonate(CAB-F), Fe-Mn oxide(FMO-F),
organic matter (OM-F) and residual fraction(RES-F) in incubation experiments. At
the end of incubation, the FDC of soil exchangeable Cd decreased from 72.0%-88.0%
to 2.4%-10.7%. The decreasing effect of zeolite on the concentration and FDC of
exchangeable Cd (EX-F) increased with the increase of zeolite, and the decreasing
effect of nano zeolite (NZ) was better than that of ordinary zeolite (OZ). During
the culture of 28 d, the concentration of different Cd fractions in soil was in
order of EX-F>RES-F>FMO-F>CAB-F>OM-F under different pH conditions. Exchangeable
fraction Cd was the dominant fraction of Cd in soil during the whole incubation.
Soil CEC had significant negative correlation with soil exchangeable Cd (EX-F)
(P<0.01), and significant positive correlation with the concentrations of Fe-Mn
oxide(FMO-F) and organic matter (OM-F) in soil(P<0.01). Nano zeolite and ordinary
zeolite effectively increased soil CEC, and soil CEC increased with the increase
of the pH value of soil in the zeolite treatments. Significant negative
correlation was found in soil pH with soil exchangeable Cd (EX-F)(P<0.01). The
dry weight of plant tissues in Chinese cabbage increased by 14.3%-131.4% in the
presence of nano zeolite(NZ) and ordinary zeolite(OZ), and Cd concentration of
shoot and root decreased by 1.0%-75.0% and 3.8%-53.2%, respectively. Higher
concentration and accumulation of Cd were observed in XJC3 variety than those in
SD 4 variety. Compared with ordinary zeolite (OZ), nano zeolite (NZ) was better
in increasing the biomass of Chinese cabbage as well as decreasing accumulation
of Cd in Chinese cabbage.
PMID- 29964442
TI - [Characterization of Cr Tolerance and Accumulation in Lolium perenne L. and
Pharibitis purpurea(L.) Voigt].
AB - Considering the serious pollution of heavy metal-chromium (Cr) in soil, there is
an urgent need for effective selection of Cr-tolerant plant species. In order to
gain fundamental insights into the tolerance and accumulation capabilities of
Lolium perenne L. and Pharibitis purpurea(L.) Voigt under Cr stress, a pot
experiment was conducted to investigate their growth, physiology and accumulation
characteristics under Cr(III) and Cr(VI) stress. The results showed the growth
parameters could intuitively reflect the toxicity levels of Cr for plants. For
instance, a low-level Cr(III) (<250 mg.kg-1) in soil was good for plant growth as
indicated by the significant elevation of plant height, root length and biomass
in L. perenne (P<0.05). However, Cr(VI) at all concentrations (>=25 mg.kg-1) in
the soil inhibited the growth of both plant species, and the root length was
particularly sensitive to the toxicity of Cr. The physiological parameters of
plant represented both the toxicity of Cr and the tolerance of plants under Cr
stress. A decrease of root activity and an increase of malonaldehyde content were
observed under Cr stress, which indicated the physiological metabolism of plants
was disturbed. In the presence of both Cr species, the proline content increased,
which served as an indicator for both high Cr toxicity and increase of osmotic
balance in plants. A rise in SOD and POD activity reflected the defense ability
of plants against oxidative stress caused by Cr. In addition, the Cr-accumulation
related parameters were the major standards for tolerant species selection. The
Cr(VI) accumulation capacities of both plant species were greater than their
Cr(III) accumulation capacities. The maximum accumulation amounts of L. perenne
and P. purpurea reached 957.4 mg.kg-1 and 743.3 mg.kg-1 in roots and 394.7 mg.kg
1 and 340.4 mg.kg-1 in shoots, respectively. In comparison with P. purpurea, L.
perenne displayed a stronger Cr accumulation capacity in roots with a maximum
bioaccumulation factor of 15.55. However, the transport ability of P. purpurea
was superior to L. perenne. All of the parameters demonstrated that both L.
perenne and P. purpurea could be used as alternative plants for phytoremediation
of Cr-contaminated soil.
PMID- 29964443
TI - [In vitro Metabolism of Volatile Methyl Siloxanes].
AB - Volatile methyl siloxanes (VMSs) are of great concern in the past few years due
to their high production volume, ubiquitousness in the environment and
toxicities. The bioaccumulation of VMSs is reported to be sensitive to their
metabolism rates, however, little is known about their metabolic rates in aquatic
organisms. The present study measured intrinsic clearance rates of 16 common VMSs
(D3-D6 and L3-L14) incubated in liver microsomes of weever and quail. The
intrinsic clearance rates of VMSs in weever microsomes were 0-0.031 mL.(h.mg)-1.
The fact that D5 exhibited no significant decline trend in the incubations with
liver microsomes of weever corresponded with its trophic magnification behaviour
in aquatic food webs. L4-L14, similar to D5, were also persistent in microsomes,
suggesting the high bioaccumulation potentials of the chemicals. The intrinsic
clearance rates of VMSs incubated in quail microsomes [0.25-1.7 mL.(h.mg)-1] were
significantly higher than those incubated in weever microsomes. The relatively
high biotransformation rates of D3-D6 and L3-L14 suggested that these compounds
may not exhibit high biomagnification potentials in birds. B[a]P was used as a
benchmark chemical to normalize variations in determining the metabolism rates
among batches, and the structure-activity relationships were explored for the
normalized intrinsic clearance rates of quail microsomes. Hydrophobicity and
electric properties were found to be major factors influencing the bird
microsomal intrinsic clearance rates of VMSs.
PMID- 29964444
TI - [Efficiency of Aerobic Co-composting of Urban Sludge and Chinese Medicinal Herbal
Residues].
AB - With Chinese medicinal herbal residues and municipal sludge as raw materials for
co-composting experiment, the effect of the material ratio and addition time of
Chinese medicinal herbal residues on the composting efficiency were investigated,
including the change of the temperature, organic matter, ammonia nitrogen, and
activity of protease. The best composting conditions were determined based on the
results. The experimental results showed that the temperature of the pile was
raised in the presence of 60 g Chinese medicinal herbal residues as carbon source
and 300 g municipal sludge, the ammonia volatilization was reduced and the
activity of protease was improved. The ammonia volatilization was reduced by
35.9% and the activity of protease was increased by 80.5% in 15 d, respectively.
Especially, in the early stage, addition of Chinese medicinal herbal residues as
conditioner could increase the organic matter degradation. Thus, the composting
process was accelerated. Changes in the UV-visible and fluorescence
characteristics of dissolved organic matter (DOM) during the co-composting
process were discussed. The treatment with Chinese medicinal herbal residues
improved the maturity of the compost. Moreover, phospholipid fatty acid (PLFA)
method was used to estimate the microbial community structure changes. It showed
that the number of microbial community such as fungi and Gram negative bacteria
increased with addition of Chinese medicinal herbal residues.
PMID- 29964445
TI - [Concentration Characteristics of PM2.5 in Beijing During Two Red Alert Periods].
AB - Variations of PM2.5 concentrations and effects of pollution control measures
during two red alert periods in 2015 in Beijing were analyzed based on
atmospheric pollutant monitoring data. The results showed that during the first
red alert, the highest hourly-averaged PM2.5 concentration occurred at 19:00 on
9th December with a value of 282 MUg.m-3 and the highest hourly PM2.5
concentration appeared at Yongledian station which is near the southeast border
of Beijing, with the peak concentration of 496 MUg.m-3. During the second red
alert, the highest hourly-averaged concentration of PM2.5 occurred at 20:00 on
22th with a value of 421 MUg.m-3. The highest hourly PM2.5 concentration was
monitored at Liulihe station which is near the southwest border of Beijing, with
the peak concentration of 831 MUg.m-3. During the duration period of both red
alerts, the concentrations at the southern stations were higher than those at
downtown stations and the PM2.5 concentrations at northern stations were found to
be the smallest. The difference between these two red alerts was that during the
second red alert, the PM2.5 concentrations in southern Beijing were significantly
higher than those in the northern area, while the magnitude of this south-to
north gradient was much smaller during the first one. During the second red
alert, up to 93% of Beijing area showed an average PM2.5 concentration of above
150 MUg.m-3, which was much larger than that in the first one. The meteorological
conditions during the two red alerts were both not conducive to the spread of
pollutants. Formation of secondary pollutants and regional pollutant transport
existed as well. Though the stagnant weather conditions were in favor of the
development of severe pollution, large regional-wide pollutant emission was the
main reason for these two heavy air pollutions in Beijing. PM2.5 concentrations
were decreased by 20%-25% after the implementation of emergency response
measures, which showed the significance of emission reduction in air pollution
control.
PMID- 29964446
TI - [Response of Human Respiratory Height PM2.5 Variation Characteristics to
Meteorological Factors During Winter Haze Days in Beijing].
AB - In order to investigate the influence of meteorological factors on the variation
characteristics of PM2.5 in Beijing. According to the survey of PM2.5 mass
concentration in height of human respiration, humidity, the direction of the
wind, wind speed and temperature. Using the methods of correlation analysis and
nonlinear regression analysis, the effects of meteorological factors on the
formation and variation of PM2.5 mass concentration in light and moderate air
pollution days and heavy pollution were discussed respectively. The results
showed that:1 On mild to moderate pollution days, if the temperature was low, the
daily average wind speed was low, the humidity was high, then the humidity was
the decisive influencing factor of PM2.5 mass concentration; if the temperature,
wind speed and humidity were all high, then the variation of PM2.5 mass
concentration was influenced by the combined action of these three; when the
temperature, humidity and wind speed were all low, then the PM2.5 mass
concentration was mainly affected by the first two factors. This suggested that
changes in the height of the human respiration PM2.5 mass concentrations were
extremely sensitive to small changes in meteorological factors; 2 During the
process of air quality turning from good to heavily polluted, the accumulation of
PM2.5 mass concentration was mainly due to the weak air turbulence, coupled with
the high humidity, in addition, the northwest wind and northeast wind were larger
during the daytime but the duration was shorter, while the southeast and
southwest wind speed at night was lower with longer duration, which was conducive
to pollutant accumulation;3 Short-term low amount of snow decreased the
temperature and increased the air humidity, which not only could not reduce the
PM2.5 mass concentration, but rather increased it by 72%, resulting in the jump
phenomenon of particle concentration; 4 When the wind speed reached up to 2.0 m.s
1 and lasted for two hours, the local PM2.5 mass concentrations could be reduced
to some extent, but it could not completely change the air quality situation.
Only when the wind speed was greater than 3.5 m.s-1 and lasted for more than 4
hours, the fine particulate matter in the air could be quickly diffused and the
air quality was changed from heavy pollution to excellent.
PMID- 29964447
TI - [Pollutional Characteristics and Sources Analysis of Polycyclic Aromatic
Hydrocarbons in Atmospheric Fine Particulate Matter in Lanzhou City].
AB - Polycyclic aromatic hydrocarbons (PAHs) are a group of important toxic compounds.
In order to detect the pollutional characteristics of atmospheric PAHs in Fine
Particulate Matter (PM2.5), a total of 60 PM2.5 samples were collected in Lanzhou
City during the winter of 2012 and summer of 2013. The GC/MS measurement results
of the samples demonstrated the averagely total mass concentrations of the most
significant 16 homologues of PAHs were (191.79+/-88.29) ng.m-3 and (8.94+/-4.34)
ng.m-3 in winter and summer respectively, indicating a higher pollution level in
winter. In winter, the snowfall was the most important meteorological factor for
the decrease of PAHs mass concentration in PM2.5. The percentages of PAHs with 4
rings were the highest in both winter (51.40%) and summer (49.94%) in Lanzhou.
The percentage of PAHs with 5-6 rings in summer (41.04%) was higher than that in
winter (24.94%). However, the percentage of PAHs with 2-3 rings in summer (9.03%)
was lower than that in winter (23.67%). Based on the analysis of characteristic
ratios, we concluded that the PAHs in atmospheric PM2.5 in Lanzhou were mainly
sourced from coal and vehicle emissions in winter, especially the diesel
vehicles. The absolute contributions of all possible PAHs pollution sources were
insignificant in summer, with relatively higher contribution from gasoline
vehicles.
PMID- 29964449
TI - [Impact of Marine-atmospheric Process on Aerosol Number Size Distribution in the
South China Sea].
AB - The shipboard measurements of aerosol number concentration from August 28th to
October 13th, 2012 were conducted to analyze the characteristics of temporal
spatial distribution and number size distribution of marine aerosol in the South
China Sea. The impact of meteorological condition on the marine aerosol was also
analyzed in this paper. The result showed that the temporal-spatial distribution
and number size distribution of marine aerosol were influenced by the backward
trajectory of the air masses and the time they spent over the sea, and the
meteorological conditions in the local sea area such as wind speed, wind
direction, temperature, relative humidity and cloud cover. In terms of temporal
spatial distribution of marine aerosol in the South China Sea, the aerosol in the
sea areas under the influence of continental air mass concentration showed much
higher concentration than that in the clean maritime air mass (2300 cm-3 vs. 1200
cm-3). During the ship observation, three kinds of number size distribution of
marine aerosol were found and classified:polluted type, marine type 1 and marine
type 2 (clean). All the distributions had a similar sub-micron mode and a similar
coarse mode. The marine type 2 (clean) had the same distribution shape as
polluted type except that the value of concentration was much lower. The sub
micron peak of marine type 1 appeared near 0.08 MUm and its concentration was
significantly higher than that of marine type 2 (clean). Non-precipitating clouds
as well as abundant moisture contributed to the growth of ultrafine particles to
the size of accumulation mode aerosol (0.05-0.12 MUm). Number concentration of
particles in this range showed weak positive correlation with wind speed since
wind can enhance the efficiency of sea-air exchange and accelerate the release of
gas precursors of sulfate aerosol to the atmosphere. The concentration of coarse
particles ranging from 0.5-6 MUm in diameter strongly depended on the wind speed,
and the correlation coefficient reached a value of 0.7.
PMID- 29964448
TI - [Determination and Source Apportionment of Aromatic Acids in PM2.5 from the
Northern Suburb of Nanjing in Winter].
AB - Atmospheric particulate samples of PM2.5 were collected from the northern suburb
of Nanjing in December, 2014, and a LC-MS method was optimized for the
determination of aromatic acids in PM2.5; The concentrations of major water
soluble ions, organic carbon and elemental carbon were also determined. The
quantification results showed that the average total concentration of five
aromatic acids we have determined was (50.01+/-16.05) ng.m-3, and the average
concentrations of terephthalic acid, phthalic acid, trimellitic acid, 4
methylphthalic acid and iso-phthalic acid were (34.54+/-12.79),(8.14+/
3.34),(2.27+/-1.39),(1.68+/-0.77) and (1.08+/-0.43) ng.m-3, respectively. The
different source apportionments of atmospheric particulate were analyzed by
principal component analysis/absolute principal component scores (PCA/APCS)
receptor model. The results of source apportionment showed that the main sources
of Phthalic acid, Trimellitic acid and 4-methylphthalic acid were mainly
secondary transformation, and primary emissions such as vehicle exhaust
contributed less to Trimellitic acid; Secondary transformation and biomass
burning made the most significant contributions to iso-Phthalic acid and vehicle
exhaust contributed less; The sources of Terephthalic acid were primary emissions
such as biomass burning and vehicle exhaust.
PMID- 29964450
TI - [Assessment of Heavy Metals Pollution and Its Health Risk of Atmospheric Dust
Fall from East Part of Junggar Basin in Xinjiang].
AB - In order to evaluate the contamination and health risk of heavy metals from
atmospheric dust fall in Zhundong opencast coalfield in Xinjiang, samples of
atmospheric dust fall were collected from 52 sampling sites covering the entire
region and the contents of Zn, Cu, Cr, Pb, Hg and As were tested and analyzed.
The contamination was assessed by geo-accumulation index method, and the risk to
human health was assessed using the US EPA Health Risk Assessment Model. The
results showed that:The contamination of heavy metals from atmospheric dust fall
had a significant difference, in the order of Zn > Cr > Cu > As > Pb > Hg, and
the average contents were higher than the soil background of Changji. The
coefficient of variation of Hg, Cu and As was 381.91%, 99.94% and 97.82%, and
human activities had a greater impact on them. The correlation coefficients in 6
heavy metals were complex, the correlation coefficients among Zn-Cu-Cr were more
relevant than Hg-As-Pb. The assessment results of geo-accumulation index
indicated that the Zn pollution in the atmospheric dust fall should be classified
as extreme degree, and that of Cu, Pb, As as between slight and extreme degrees,
and Hg as practically uncontaminated. The exposure content of carcinogenic risk
and non-carcinogenic risk of the study area had little difference. It was HQCr >
HQAs > HQZn > HQPb > HQCu > HQHg, the total non-cancer hazard index was 0.258,
the non-cancer hazard indexes were both lower than their threshold values,
suggesting that they would not harm the health. The carcinogenic risk hazard
indexes were in the order of CRAs > CRCr > CRPb, suggesting that Pb had no cancer
risk, while As was the most important carcinogenic factor. The average TCR was
1.95E-05, indicating that the risk was within the limit that human can tolerate.
PMID- 29964451
TI - [Variations of Stable Isotope in Precipitation and Its Atmospheric Circulation
Effect in Chongqing].
AB - Variations of hydrogen and oxygen in stable isotopes and deuterium excess in
precipitation as well as their relationship with precipitation,temperature and
ENSO (El Nino/La Nino-Southern Oscilation) were analyzed by using 100 daily
precipitation stable isotope data from April to October, 2015. The result showed
that:1 The equation of local meteoric water line (LMWL) was
established:deltaD=8.28delta18O+12.34, the intercept and slope of which were
greater than the global meteoric water 1ine (GMWL) but was similar to most of the
southern China monsoon region.2 Both stable isotopes and deuterium excess in
precipitation indicated obvious seasonal variation in the monsoon region, high in
summer and low in winter. This was attributed to the difference in moisture
sources in different seasons. 3 In addition, no significant correlation was
detected between delta18O values in precipitation with temperature and
precipitation (r=0.03; r=0.12). But it was sensitive to atmospheric circulation
effect, and was positively correlated with ENSO.delta18O values in precipitation
and deuterium excess in precipitation clearly recorded the La Nino and El Nino
conversion process between 2014 and 2015. During the El Nino event, the delta18O
and d values became obvious on the high side, and the changes were the opposite
during La Nino.
PMID- 29964452
TI - [Temporal Dynamics of Stable Isotopic Composition in Lake Taihu and Controlling
Factors].
AB - The composition of hydrogen and oxygen stable isotopes in lake water is important
to the researches in hydrology, meteorology and paleoclimatology. In this study,
long-term and continuous measurement on the compositions of HDO and H218O in lake
water (deltaDL and delta18OL) was conducted over Lake Taihu, the deuterium excess
(dL) was calculated, and the temporal variability and controlling factors were
analyzed. The results indicated that 1 the variation of isotopic enrichment in
lake water was significant, ranging from -59.80/00 to -24.20/00 for deltaDL, from
-8.60/00 to -2.60/00 for delta18OL, and from -7.90/00 to 12.90/00 for dL,
respectively. In comparison to cold season, deltaDL and delta18OL were higher and
dL was lower during warm season. 2 On monthly time-scale, lake evaporation and
the ratio of total water inputs lost by evaporation controlled the isotopic
enrichment in lake water. When lake evaporation or the ratio increased, deltaDL
and delta18OL increased, but dL decreased. 3 Over Lake Taihu, the isotopic
composition in precipitation and water temperature did not control the isotopic
enrichment. The results provide scientific reference for isotope hydrology and
the researches related to the isotopic enrichment in lake water in meteorology
and paleoclimate.
PMID- 29964453
TI - [Geochemical Characteristics of Lateral Hyporheic Zone Between the River Water
and Groundwater, a Case Study of Maanxi in Chongqing].
AB - The hyporheic zone is a place where river water and groundwater mutually exchange
and mix. It plays an important role in protecting the ecology and water quality
of river water and groundwater. In order to study the geochemical characteristics
of lateral hyporheic zone in river and ground water, water temperature, dissolved
oxygen, pH, electrical conductivity were measured automatically at the hyporheic
zone of Maanxi in Chongqing. The concentrations of ions in water and elements in
sediment within the hyporheic zone were also analyzed. The results showed that
the hydrochemical species of lateral hyporheic zone in Maanxi was HCO3-Ca.Mg.
Affected by the infiltration of river water, the coefficient variations of water
temperature, dissolved oxygen, pH and electrical conductivity in the hyporheic
zone were lower than those observed in the river under the buffer action. Along
with the farther distance from the riverbank, an anoxia redox environment was
formed in the hyporheic zone due to a physical, chemical and biological
interactions. An acid and alkali environment was also formed with a decreasing pH
trend near the riverbank and hyporheic zone. Under its influence, concentrations
of K+, NH4+-N, NO3- and SO42- decreased. Mn, electrical conductivity, and the
concentrations of Ca2+, Mg2+, Ba2+ and Sr2+ firstly increased and then decreased,
while the concentrations of Fe, Al3+ were elevated. Affected by the long-time
interaction of river water and groundwater, the elementary concentrations in the
sediment were relatively high at the place of about 30 cm away from the
riverbank. This consequently formed a hydrogeochemical gradient in the hyporheic
zone. The boundary of the hyporheic zone was inferred at 30 to 50 cm away from
the riverbank, whereas the boundary of shallow hyporheic zone was located at 10
cm away from the riverbank. In the process of river water recharging groudnwater,
hyporheic zone of river and groundwater played an important role in the
purification of water quality.
PMID- 29964454
TI - [Variations of CO2 Exchange Fluxes Across Water-air Interface and Environmental
Meaning in a Surface Stream in Subtropical Karst Area, SW China].
AB - CO2 cycle process or sources/sinks are not only the basis of understanding and
responding to global climate change, but also the core of the current global
climate change research. Gas exchange across water-air interface in terrestrial
surface water is an important way of nutrient elements (carbon, nitrogen)
exchange between aquatic ecosystems and ambient air. Escaping CO2 gas from
surface water is also actively involved in the modern carbon cycle. In the
material cycle in karst regions, CO2 plays a key role in karst processes, driving
the formation of karst features. Karst groundwater with high water CO2 partial
pressure (pCO2) often shows highly positive CO2 concentration gradient to
atmosphere after it is discharged to surface, so the evaluation of CO2 exchange
fluxes across karst water-air interface is important for karst carbon cycle
research. This paper researched CO2 exchange fluxes across water-air interface in
the karst surface stream in detail which was fed by Guancun subterranean stream
in Liuzhou city, Guangxi province. Closed static chamber method and portable hand
holding CO2 sensor (GM70) were both employed in CO2 exchange fluxes monitoring.
The results showed that CO2 degassing was the mainly form of CO2 exchange across
the steam water-air interface. CO2 degassing flux in subterranean stream outlet
(G1 site) ranged from 139.48 to 890.84 mg.(m2.h)-1 with an average of 445.72
mg.(m2.h)-1. CO2 degassing flux in stream downstream site (G2 site) ranged from
16.54 to 844.18 mg.(m2.h)-1 with an average of 159.81 mg.(m2.h)-1. The CO2
degassing flux in G1site was higher than that in G2 site. CO2 degassing fluxes in
rainy season in both G1 and G2 site were higher than those in dry season. Stable
carbon analysis of CO2 gas (delta13C-CO2) found that CO2 degassing from karst
stream might influence air CO2 carbon isotope near water surface, which resulted
in the more negative delta13C-CO2 value with the increase of CO2 degassing flux.
Significant spatio-temporal variations of delta13C-CO2 were found, and the
delta13C-CO2 in the rainy season was more negative than that in dry season and
delta13C-CO2 in G1 site was more negative than that in G2 site. As a result of
stream CO2 degassing, the hydrochemical characteristics of steam varied along
stream running, which resulted in decrease of HCO3-, EC and pCO2 and increase of
pH, SIc and delta13C-DIC in the stream.
PMID- 29964455
TI - [Spectral Characteristics of Dissolved Organic Matter (DOM) Releases from Soils
of Typical Water-Level Fluctuation Zones of Three Gorges Reservoir Areas:UV-Vis
Spectrum].
AB - Water-level fluctuation zone is an important area in Three Gorges Reservoir
areas, because dissolved organic matter (DOM) releases from submerged soils is a
crucial source of DOM in overlying waters when flooding occurs. But there was
little qualitative and quantitative analysis for DOM. In this study, soils of
four typical water-level fluctuation zones were selected to conduct simulated
flooding experiment. Also, UV-Vis spectroscopy was utilized to investigate the
DOM spectral characteristics in two individual flooding sets including ambient
(open air) and anoxic conditions. The results showed, for all soils, the DOM
release patterns all showed a "rapid release, then decrease, and final dynamic
equilibrium" trend. Also, through calculations of DOM releasing rates and fluxes,
DOM releases clearly showed a feature of "source-sink dynamic exchange". By
comparison between two flooding treatments, although DOC and CDOM didn't show any
significant differences, but higher aromaticity (SUVA280) was observed in anoxic
experiment. In contrast, spectra slope ratio (SR) was insensitive to redox
conditions of different flooding. Meanwhile, correlation between DOC and CDOM in
anoxic was also higher than that in ambient flooding. Additionally, obvious
differences among soils from different sampling sites were observed, Shibao Zhai
(SB) of which showed the greatest releasing potential. Considering the various
soil properties, soil organic matter amounts in soils is one of the key factors
to explain the differences among sampling sites, but other geochemical factors
should also be considered in the processes of DOM releases. Summarily, only
focusing on the changes of DOC concentrations in submerging process is not enough
to comprehensively describe the DOM release characteristics.
PMID- 29964456
TI - [Spectral Characteristics of Dissolved Organic Matter (DOM) Releases from Soils
of Typical Water-Level Fluctuation Zones of Three Gorges Reservoir
Areas:Fluorescence Spectra].
AB - As an important sources of dissolved organic matter (DOM) in aquatic system, DOM
releases from flooding or submerged soils is a key process in water-level
fluctuation zones. In this study, four typical sites in water-level fluctuation
zones of Three Gorges Reservoir areas were selected to conduct simulated soil
flooding experiments, under ambient (open air) and anoxic conditions. By using
fluorescence spectrum technique, the dynamic and geochemical characteristics of
DOM releases from flooding soils were investigated. Results showed that the trend
or model of DOM releases observed by fluorescence spectrum in all soils from four
sampling sites was similar to the observation by UV-Vis spectrum. Fluorescence
property of DOM releases showed an important contribution to DOM fluorescence in
overlying waters. The rapid releases at initial stage and removal mechanism for
later dynamic equilibrium were crucial to explain the dynamic "source-sink"
equilibrium in whole flooding period. Effect of inorganic mineral adsorption
desorption on humic-like components (A and C peaks) was significant. Also, impact
of microbial utilization on protein-like components (B and T peaks) was
confirmative. Additionally, all DOM samples had "autochthonousness plus
allochthonousness" property. Except Shibaozhai (SB) site in Zhongxian county,
during the whole flooding period, all three other sites didn't show any
significant difference between ambient and anoxic conditions. They could be
explained by the high heterogeneity of soil property including minerals and
organic components. Meanwhile, both the UV-Vis and fluorescence spectra were
complementary for each other, and they evidentially showed that the "source-sink"
(release and removal) mechanism in DOM releases from submerged soils was the core
to decide the dynamics of DOM in overlying waters. Importantly, DOM showed higher
aromaticity and humification at the initial release stage when flooding occurred,
as well as the greater terrestrial source characteristics, which further helped
to explain the environmental fates of pollutants in these environmental sensitive
areas. It would also be useful for unveiling the role of DOM in environmental
system in future.
PMID- 29964457
TI - [Distribution Characteristics and Health Risk Assessment of Thirteen Sulfonamides
Antibiotics in a Drinking Water Source in East China].
AB - Trace levels of residual antibiotics in drinking water sources may threaten
public health and becomes a serious issue in modern society. Occurrence and
distribution of 13 sulfonamides antibiotics in a drinking water source in East
China were investigated using solid phase extraction-high performance liquid
chromatography-tandem mass spectrometry. The results revealed that all 13
sulfonamides were detected with the total concentrations ranging from 10.5 ng.L-1
to 238.5 ng.L-1. Sulfamethoxazole (SMX) and sulfonamide (SAM) presented the 100%
detected frequency, and the maximum concentrations reached 107.0 ng.L-1 and 43.1
ng.L-1, respectively. Sulfonamides contamination levels in the inlet were
relatively higher than those in the outlet. The concentration of SMX was
substantially unchanged in different positions of drinking water source. Seasonal
variation of sulfonamide concentration showed that the concentrations were higher
in winter and spring compared with those in summer and autumn. The range of total
sulfonamides concentration detected in winter and spring was from 110.8 ng.L-1 to
117.9 ng.L-1, which was 3.6-3.8 times higher than those in summer and autumn.
Human health risk characterization of residual sulfonamides in drinking water
source was based on the assessment of risk quotients (RQs) for which different
life stages were taken into account. The results showed that no sulfonamides had
a RQs higher than 1. Trimethoprim (TMP) was the most risky antibiotic to the 0-3
months old infants with RQs reaching 0.001. Although the sulfonamides detected in
the drinking water source do not pose any risk to the peoples' health, the
implication of long-time exposure and comprehensive risk still deserve attention.
PMID- 29964458
TI - [Concentrations of Ketamine and Norketamine in the Water Environment in Beijing].
AB - Concentrations of ketamine (KET) and its metabolite, norketamine (NK) in sewage
water and surface water in Beijing were examined by HPLC-MS/MS. Samples were
collected from all the thirteen sewage treatment plants in the urban area and
four rivers flowing through the city. Average influent concentrations of KET and
NK in 2013 summer ranged from
beta-P > ATP-P. The similar toxic tolerant abilities to As(V) of M. aeruginosa
under beta-P and ATP-P conditions were lower than that of EC50 under DIP
conditions by one to five orders of magnitude.
PMID- 29964465
TI - [Removal Behavior of Ibuprofen and Diclofenac in Different Constructed Wetlands].
AB - Ibuprofen and diclofenac, two commonly used pharmaceuticals, were studied to
evaluate the removal behavior of acid pharmaceuticals in constructed wetlands
(CWs) with different flow types, vegetation and seasons. It was shown that flow
types influenced the results significantly. The average removal efficiency of
ibuprofen in horizontal subsurface flow (HSSF) and vertical subsurface flow
(VSSF) CWs (69% and 60%, respectively) was significantly higher than that in
surface flow (SF) CWs (26%). For diclofenac, SF CWs (58%) was significantly
higher than HSSF and VSSF CWs (49% and 43%, respectively). In addition, the
presence of plants improved the efficiency of ibuprofen, while it had no
significant influence on the removal of diclofenac. Paired t-test found out that
summer and autumn season variety had little impact on the removal. Furthermore,
the removal of diclofenac and DO, as well as COD, showed very significant
negative correlations. Opposite to diclofenac, the removal of ibuprofen had good
positive correlations with dehydrogenase activities. The research indicated that
aerobic biodegradation behavior mainly took place in ibuprofen, yet anaerobic
biodegradation and photolysis behavior were expected for diclofenac.
PMID- 29964466
TI - [Influence of Chemical Pre-oxidation on Chloral Hydrate Formation of Threonine].
AB - The influences of different chemical pre-oxidants, including sodium hypochlorite
(NaClO), chlorine dioxide (ClO2), permanganate (KMnO4), hydrogen peroxide (H2O2),
ozone (O3) and ozone/hydrogen peroxide (O3/H2O2), on chloral hydrate (CH)
formation were studied for threonine that has the highest special chloral hydrate
formation potential (SCHFP). Suitable pre-oxidants and corresponding optimal
doses were determined to provide guidance for controlling chloral hydrate (CH)
formation during drinking water treatment. The results indicated that the pre
oxidants that could decrease CH formation for one day incubation time (CH1d) were
H2O2, ClO2, KMnO4 and NaClO, and the corresponding suitable doses were 3, 0.5,
0.6 and 0.5 mg.L-1, and the corresponding CH1d removal rates were 61.54%, 47.63%,
29.77% and 10.94%, respectively. The pre-oxidants that could decrease CH
formation potential (CHFP) were KMnO4, NaClO, H2O2 and ClO2, and the
corresponding suitable doses were 0.6 mg.L-1, 0.5 mg.L-1, 3 mg.L-1 and 0.5 mg.L
1, and the corresponding CHFP removal rates were 41.01%, 33.38%, 8.36% and 2.40%,
respectively. In addition, O3 and O3/H2O2 were not suitable for controlling CH in
the conventional treatment process because they could increase CH1d and CHFP.
PMID- 29964467
TI - [Activated Carbon Supported Co3O4 Catalysts to Activate Peroxymonosulfate for
Orange G Degradation].
AB - Activated carbon supported cobalt catalysts (Co/AC) were prepared through wet
impregnation and high temperature calcination methods. The X-ray diffraction
(XRD), scanning electron microscopy (SEM) and energy dispersive X-ray
spectroscopy (EDS) characterization results showed that Co3O4 was the major form
of Co species distributed on AC. The performance of Co/AC was evaluated as
catalyst to activate peroxymonosulfate (PMS) to produce sulfate radicals (SO4-.)
for Orange G (OG) degradation in solution. The activation mechanism and several
influential factors were also investigated. The results demonstrated that SO4
.played a dominant role in OG degradation. And the degradation efficiency of OG
increased with increasing Co/AC dosage, higher PMS concentration or elevating
reaction temperature. Initial pH had a significant effect on OG degradation, with
pH range of 4 to 8 as the optimal pH for degradation. In addition, the strong
acidic or alkaline conditions were unfavorable for OG degradation. A dual effect
of chloride ions (Cl-) was observed. The high Cl- concentration promoted
degradation, while low concentration led to inhibition. The Co/AC also exhibited
excellent reusability and its activating performance toward PMS was still
observed after 6 rounds of tests. Finally, the degradation process and
intermediate products of OG were analyzed with UV-visible spectroscopy and gas
chromatography-mass spectrometry (GC/MS).
PMID- 29964468
TI - [Kinetics for Degradation of Orange G with Peroxymonosulfate Activated by Carbon
Nanotubes].
AB - Carbon nanotube (CNT) was used as an activator to activate peroxymonosulfate
(PMS) to degrade azo dye orange G (OG) in aqueous solution. The results indicated
that CNT exhibited a much better performance in activating PMS to decolorize OG
than activated carbon (GAC), with 99% decolorization of OG achieved within 45
min. Afterwards, the degradation mechanism of OG in CNT activated PMS system was
explored, and SO4-.was found to be dominantly responsible for OG degradation,
which mainly took place on the surface of CNT. Effects of various factors,
including temperatures, initial concentration of OG, CNT loadings, PMS dosage,
and initial pH, on degradation of OG were then investigated, and OG degradation
in these cases well conformed to first-order kinetics. From the analysis of UV
vis spectra of OG during the reaction, the peaks at 479 nm and 330 nm were found
to be significantly decreased, suggesting that the azo band and naphthaline ring
were destructed, respectively. Finally, TOC analysis indicated that a certain
degree of OG mineralization was obtained in CNT activated PMS system.
PMID- 29964469
TI - [Removal of Chloramphenicol in Wastewater by Electrocatalytic Reduction with
Carbon Nanotubes-Modified Electrode].
AB - In order to develop treatment technique for antibiotics and protect water
environmental quality, the carbon nanotubes (CNTs) modified electrode was
prepared with surfactant-assisted dispersion, the electrocatalytic reduction
ability and kinetic characteristics of chloramphenicol were studied using the
modified electrode, and the reduction mechanism was investigated preliminarily.
The results showed that CNTs could be effectively dispersed by dihexadecyl
phosphate (DHP), and the removal rate of 2 mg.L-1 chloramphenicol reached 97.21%
after 24 h reduction using the modified electrode under the optimal ratio of CNTs
to DHP and the modified amount of CNTs dispersion. The kinetic process of the
electrocatalytic reduction could be well described by the first-order reaction
kinetic model, and the removal rate constant and half-time were 0.1574 h-1 and
4.40 h, respectively. The reduction products were identified by liquid
chromatography-tandem mass spectrometry (LC-MS/MS) to reveal the possible
reduction pathway, which indicated that the electrocatalysis could not only
reduce nitro-group in chloramphenicol, but also further reduce carboxyl group and
dechlorination, and thus significantly decrease its toxicity.
PMID- 29964470
TI - [Removal of AOX, Chroma and TOC in Chemical Dyestuff Wastewater with Iron Scraps
Fenton-Coagulation Combined Process].
AB - Iron scraps-Fenton-coagulation process was applied to chemical dyestuff
wastewater. The removal performance of absorbable organic halogens(AOX), chroma
and total organic carbon (TOC) was investigated at different molar ratios of Fe2+
to H2O2 (1:3-1:15), iron scraps reaction time (2-5 h) and Fenton reaction time
(20-80 min). The results showed that the removal ratios of AOX, chroma and TOC
firstly increased and then decreased with the decrease of the molar ratio of Fe2+
to H2O2, while continuously increased with the increase of iron scraps and Fenton
reaction time. The optimal condition was determined as Fe2+:H2O2 ratio of 1:8,
iron scraps reaction time of 4 h and Fenton reaction time of 60 min, under which
94.2% of AOX, 93.7% of chroma and 27.2% of TOC were removed. A comparison study
revealed that the iron scraps-Fenton-coagulation combined process could achieve
much better removal of AOX, chroma and TOC than any other single or combined
processes of iron treatment, Fenton oxidation and coagulation. GC-MS analysis
revealed that halogenated compounds and anilines were efficiently removed, as
well as nitrobenzenes, phenols, benzaldehydes, ethers, nitriles and heterocyclic
compounds..OH was found to devote much in the Fenton reaction according to the
tert-butyl alcohol trapping hydroxyl radicals test.
PMID- 29964471
TI - [Removal of AOX in Activated Sludge of a Chemical Pharmaceutical Industry with
Fenton Oxidation].
AB - This study aimed to remove AOX (adsorbable organic halogens) with Fenton
oxidation from activated sludge in a chemical pharmaceutical industry. The
influences of H2O2 dosage, Fe2+ dosage and reaction time were investigated, based
on which the reaction conditions for AOX removal were optimized, and the reaction
mechanism was discussed. The optimized reaction conditions were as follows:0.90
mol.L-1 of H2O2, 0.045 mol.L-1 of Fe2+[n (Fe2+):n (H2O2) of 1:20] and reaction
time of 2 h. Under the optimized conditions, 70.7% of AOX in the sludge and 78.5%
of AOX in the supernatant were removed. GC-MS analysis revealed that eleven
organic halides were detectable in the original sludge. After Fenton reaction,
only three organic halides were detectable, and their peak areas were reduced by
40%-50%. Toxic and hazardous non-AOX organic matters such as xylene, diisobutyl
phthalate were also effectively removed.
PMID- 29964472
TI - [Performance Evaluation of a Pilot-scale Microbubble-aerated Biofilm Reactor].
AB - A pilot-scale microbubble-aerated biofilm reactor was operated to treat campus
domestic wastewater and its performance was evaluated and compared with
conventional biological treatment processes. The results indicated that when the
raw campus domestic wastewater was treated in the pilot system, the average COD
removal efficiency and loading rate removed were 57.0% and 2.68 kg.(m3.d)-1; the
average ammonia nitrogen removal efficiency and loading rate removed were 17.4%
and 0.17 kg.(m3.d)-1; the average total nitrogen (TN) removal efficiency and
loading rate removed were 15.8% and 0.21 kg.(m3.d)-1; and the average oxygen
utilization efficiency reached 100%. When the effluent of biological contact
oxidation tank with poor biodegradability was treated in the pilot system, the
average COD removal efficiency and loading rate removed were 46.0% and 1.53
kg.(m3.d)-1; the average ammonia nitrogen removal efficiency and loading rate
removed were 17.1% and 0.32 kg.(m3.d)-1; the average total nitrogen (TN) removal
efficiency and loading rate removed were 14.1% and 0.28 kg.(m3.d)-1; and the
average oxygen utilization efficiency was higher than 50%. Furthermore, the
contaminant removal performance of the pilot system was much more efficient than
conventional biological contact oxidation tank and biological aeration filter
tank with the same influent quality, since oxygen transfer and oxygen utilization
could be enhanced by microbubble aeration.
PMID- 29964473
TI - [Nitrogen Removal Performance of Novel HABR Reactor over CANON Process].
AB - The startup of novel hybrid anaerobic baffled reactor (HABR) and the feasibility
of completely autotrophic nitrogen removal over nitrite (CANON) process were
studied. The reactor was operated by gradually decreasing HRT to improve total
nitrogen load. After startup, the change of nitrogen concentrations,
conductivity, pH and MLSS was measured along the reactor, and then the microbial
morphology and spatial structure of bacteria were defined. The test results
indicated several points:under the experimental condition of an average NH4+-N of
40 mg.L-1 in influent, the quick start-up process was successfully achieved by
continuous operation within 89 days, and stabilized over 187 days. The average
NH4+-N and TN concentrations of effluent were below 2 mg.L-1 and 10 mg.L-1
respectively, the average removal efficiencies of NH4+-N and TN reached above 96%
and 83% respectively, and a NRR of 0.15 kg.(m3.d)-1 was obtained. During the
stable phase, the concentrations of NH4+-N and TN gradually declined along the
reactor, while the concentrations of NO2--N and NO3--N remained constant at
relatively lower values. The highest nitrogen removal efficiency of ammonia
occurred in compartment 1, and the reason was confirmed by SEM and FISH
microbiological analysis that enriched functional bacteria of AOB and AnAOB
coexisted in compartment 1.
PMID- 29964474
TI - [Characteristics of a Combined Heterotrophic and Sulfur Autotrophic
Denitrification Technology for Removal of High Nitrate in Water].
AB - A combined heterotrophic and sulfur autotrophic denitrification technology for
NO3--N wastewater treatment was started up by adding elemental sulfur in the
heterotrophic denitrifying reactor, and the characteristics of pH constant and
sludge reduction were studied. The results showed that the sulfur autotrophic
denitrification bacteria in heterotrophic denitrifying reactor could achieve
rapid growth. After running for 65d, TOC/N was controlled between 0.65 and 0.75,
and the combined denitrification process did not require external alkalinity
supplementation as the alkalinity need of autotrophic denitrifiers was
supplemented by the heterotrophic denitrifiers. After running for 116d, the total
nitrogen removal rate reached above 85%, and the denitrification efficiency was
kept steady at 2.5 kg.(m3.d)-1. Compared to heterotrophic denitrification, the
sludge production was greatly reduced, which was only 60% of that produced in
combined heterotrophic and sulfur autotrophic denitrification reactor. NO2--N
accumulated by using collaborative denitrification treatment of high
concentration of NO3--N wastewater, the concentration reached 20 mg.L-1 even at
the eventual plateau stage, which would require deep processing.
PMID- 29964475
TI - [Characteristics of Microbial Community in Each Compartment of ABR ANAMMOX
Reactor Based on High-throughput Sequencing].
AB - In order to investigate the characteristics of microbial community in each
compartment of ABR anammox reactor, a five-compartment ABR reactor was used to
analyze the microbial community by Miseq High-throughput Sequencing during the
steady operational process. The results indicated that the denitrifying bacteria
coexisted in the reactor, such as Proteobacteria, Planctomycete, and Nitrospirae
bacteria, and the percentages of these three microbial populations in the sludge
were 11.66%-20.28%, 2.18%-7.94% and 0.19%-6.30%, respectively. In addition, there
were four dominant genera in the phylum Proteobacteria:Rhodoplanes, Dok59,
Rubrivivax and Bdellovibrio. Furthermore, Candidatus brocadia and Candidatus
kuenenia were the main genera in the phylum Planctomycete. The color of sludge in
the five compartments, in turn, varied from red to black. In addition, the
biodiversity index of Chao, ACE, Shannon and Simpson indicated that the richness
and diversity of microbial community increased gradually, and at the same time,
the relative abundance of Proteobacteria increased while that of Planctomycetes
gradually decreased. The above conclusion was consistent with the laws of
substrate degradation and enrichment of functional microorganisms.
PMID- 29964477
TI - [Coupling of Hydrocarbon Accumulation and Cobalt Removal During Treatment of
Cobalt Enriched Industrial Wastewater with Botryococcus braunii Biofilm Attached
Cultivation].
AB - Industrial wastewater pollution is an increasing problem. The wastewater
infiltrated cobalt is a key to purify wastewater because it is seriously
hazardous and hard to treat. Traditional management method of heavy metals in
industrial wastewater is difficult to apply. To seek for "green ecological"
feasible approaches of industrial wastewater treatment, this paper studied the
effect of industrial wastewater containing cobalt on the growth and hydrocarbon
accumulation of Botryococcus braunii SAG 807-1 with biofilm attached cultivation.
The research results obtained were as follows:B.braunii with biofilm attached
cultivation could treat industrial wastewater, and 4.5 mg.L-1 cobalt could
accelerate the accumulation of hydrocarbon while having little influence on the
growth of B.braunii, the ability of B.braunii with biofilm attached cultivation
to remove Co2+ from industrial wastewater was 1473.9 MUmol.g-1, which was much
higher than the report of P. littoralis culture. Through the study in this paper,
the theoretical basis for the coupling of production of green high energy fuel
hydrocarbon and industrial wastewater treatment was established.
PMID- 29964476
TI - [Nitrogen Removal and the Characteristics of Denitrification Bacteria Using NUA
DAS Ecofilter].
AB - A small-scale combined ecofilter was constructed using neutralized-used acid
residue (NUA) and dewatered alum sludge (DAS), and the nitrogen removal for
wastewater treatment and characteristics of denitrification bacteria using the
NUA-DAS ecofilter were studied. After the system was stabilized, the average
removal rates of COD, TN, NO3--N in the final effluents were 60%, 70% and 95%,
respectively, and the range of NO3--N concentration in the effluents was only
0.02-0.55 mg.L-1. Furthermore, the richness and similarity of three types of
functional genes (nirS, nirK and nosZ) for denitrification in different
substrates during the operation period were analyzed using PCR-DGGE method. These
results showed that the richness of all denitrification bacteria at NUA and DAS
increased remarkably after operation for 30 and 60 days compared to that in fresh
substrate, and the richness was basically the same for the same kind of gene at
the identical substrate regardless of depth gradient and operation period. The
richness of nirS, nirK and nosZ detected in the NUA and DAS followed the order of
nosZ > nirK > nirS. It was also revealed that spatial location had an apparent
influence on the community structure of denitrifying bacteria (nirS, nirK and
nosZ) but operation time had no obvious effect. Finally, nirK might be the most
suitable for the environment in the system, and the adaptive capacity of
denitrification bacteria (nirS, nirK and nosZ) in NUA could be superior to that
in DAS.
PMID- 29964478
TI - [Isolation of Raoultella sp. sari01 and Its Heterotrophic Nitrification-Aerobic
Denitrification Characteristics].
AB - The genus of Raoultella belongs to the family of Enterobacteriaceae, and some
strains of Raoultella sp. have the function of degrading chemical pollutants in
the environment. A Raoultella sp. strain was isolated from activated sludge
through enrichment cultured with heterotrophic nitrification medium. This strain
was named Raoultella sp. sari01. Single-factor and response surface methodology
experiments results showed that efficient heterotrophic nitrification of strain
sari01 occurred with sodium citrate as the carbon source, at pH of 7.0-7.5,
temperature of 30C, C/N ratio of 15, inoculation volume of 7.5% and loading
volume of 50 mL, while the removal rate of nitrogen was 99.9%, of which 33.7% was
converted to gaseous product and escaped to air, and the residual nitrogen was
fixed in cell biomass. Using nitrite and nitrate as the sole nitrogen source, the
nitrogen degradation ratios were 98.4% and 65.2%, respectively. Hence, strain
sari01 could remove nitrogen by heterotrophic nitrification-aerobic
denitrification independently, quickly and effectively, which demonstrated that
strain sari01 has the potential to be used in wastewater treatment.
PMID- 29964479
TI - [Screening and Nitrogen Removing Characteristics of Heterotrophic Nitrification
Aerobic Denitrification Bacteria SLWX2 from Sea Water].
AB - In this study, an efficient heterotrophic nitrifying-aerobic denitrifying
bacteria strain SLWX2 was screened from 7 strains isolated from Stichopus
japonicus culture ponds, with removal rates of NH4+-N, NO2--N and NO3--N up to
100%, 99.5% and 85.6% within 24 h, respectively. Through morphologic observation,
physiological characteristics and 16S rDNA sequence analysis, strain SLWX2 was
identified as Bacillus hwajinpoensis. The results of nitrogen removal
characterization experiments indicated that, when NH4+-N, NO2--N and NO3--N
existed at the same time, SLWX2 utilized NH4+-N firstly, then utilized NO2--N and
NO3--N, and removed almost all the inorganic nitrogen within 72 h, suggesting
that it could achieve simultaneous nitrification and denitrification itself. The
results of nitrogen tolerance examination indicated that strain SLWX2 showed
perfect nitrogen removal ability when the ammonia load was not above 500 mg.L-1,
nitrite load was not above 100 mg.L-1 and nitrate load was not above 200 mg.L-1,
the maximal removal of ammonia nitrogen, nitrite nitrogen and nitrate nitrogen
withinn 96 h reached 180 mg, 30 mg and 120 mg, respectively. Moreover, there was
no NO2--N accumulation during nitrification. This strain showed great potential
in biological nitrogen removal of wastewater with high salt and nitrogen from
mariculture and industries.
PMID- 29964480
TI - [Biodiversity of Thiocyanate-degrading Bacteria in Activated Sludge from Coking
Wastewater].
AB - Thiocyanate (SCN-) is one of the main sources of COD in coking wastewater, and
SCN- removal efficiency of the aerobic unit impacts the requirement of
discharging standard. Microbial population in the activated sludge plays an
important role in SCN- removal of coking wastewater treatment. However, the
community structure has rarely been reported. Using SCN- as the sole carbon and
energy source, the removal of 100 mg.L-1,300 mg.L-1 and 600 mg.L-1 SCN- by
activated sludge was studied and 454 sequencing technology was applied to
investigate the biodiversity of SCN--degrading bacteria. The results showed that
100-600 mg.L-1 SCN- could be effectively removed by acclimated activated sludge,
the higher SCN- concentration, the higher removal efficiency, but the lower
bacterial community diversity indices. The bacterial communities in initial and
acclimated sludge samples were mainly composed of Proteobacteria, Bacteroidetes,
Chlorobi, Planctomycetes, Acidobacteria, Nitrospira, Firmicutes and Unclassified
bacteria. Bacteroidetes and Proteobacteria were dominant phyla in the sludge.
Thiobacillus was responsible for SCN- biodegradation in coking wastewater, and
its abundance in three sludge samples was 3.07%, 8.63% and 0.27%, respectively.
When the concentration of SCN- was less than 300 mg.L-1, Thiobacillus was the
main degrading bacteria. While at 600 mg.L-1 SCN-, low-abundance degrading
bacteria might have synergistic degradation effect. These results have important
significance for revealing SCN- removal mechanism in the coking wastewater
treatment.
PMID- 29964481
TI - [Responses of Plankton Microeukaryotic Community to Increasing Temperatures
Created by Power Plant Thermal Discharges].
AB - Plankton microeukaryotes are primary producers, bacterial grazers and parasites
in the ocean, thus contributing essential roles in marine ecosystem stability.
For this reason, understanding how the microeukaryotic community responds to
increasing temperature created by thermal discharges is key to evaluating the
ecological and environmental consequences of a power plant. In this study, using
an Illumina sequencing based analysis of eukaryotic 18S rDNA gene, we
investigated the compositions of microeukaryotic community along a thermal
gradient caused by the discharge from the Wusha Mountain power plant in Xiangshan
Bay. The plankton microeukaryotic communities were dominated by Protalveolata,
Ciliophora, Dinoflagellata and Cercozoa. A multivariate regression tree revealed
that mircoeukaryotic diversity was primarily controlled by dissolved oxygen (DO),
followed by nitrate and temperature. Thermal discharge significantly altered the
compositions of microeukaryotic community, evidenced by an analysis of similarity
(Global RANOSIM=0.422, P<0.001). A forward selection procedure showed that the
variations of microeukaryotic community were primarily shaped by geographic
distance, DO, chlorophyll a, and temperature. The spatial distribution of
microeukaryotic community followed a distance-decay for similarity relationship,
with a turnover of 0.002. In addition, 15 sensitive eukaryotic families were
screened, the relative abundances of which were significantly associated with the
discharge-induced temperature gradient. For a given eukaryotic family, the
pattern of enrichment or decline was consistent with its known ecological
function, which could be served as bio-indicators for temperature anomalies.
Collectively, this study demonstrates the spatial pattern of microeukaryotic
community in responses to increasing temperature, and provides sensitive bio
indicators for evaluating the ecological consequences of thermal discharge.
PMID- 29964482
TI - [Characteristics of Soil Microbial Community Structure in the Rhizospheric Soil
of Ammopiptanthus mongolicus by Phospholipid Fatty Acid (PLFA)].
AB - To measure and manage plant growth in arid and semi-arid sandlands, improved
understanding of the spatial patterns of desert soil resources and the role of
soil microbes is required. The rhizosphere soils of Ammopiptanthus mongolicus in
Wuhai, Dengkou, and Alxa, Inner Mongolia, China were collected in July 2015. Soil
microbial community structure in the rhizosphere of A.mongolicus was analyzed by
phospholipid fatty acid (PLFA) combined with Sherlock microbial identification
system. The results showed that the soil microbial PLFA had a higher diversity
and 41, 31 and 48 kinds of phospholipid fatty acids were respectively detected in
the rhizosphere of A.mongolicus in three different sites. 16:0, 16:0 10-methy1,
18:1omega9c and 16:1omega7c were the dominant PLFA, and the PLFA of 16:0
(indicating bacteria) had a maximum value. However, the differences in contents
of 16:0 10-methy, 18:1omega9c and 16:1omega7c were found in the three sites. Soil
microbial community in the rhizosphere of A.mongolicus had obvious spatial
heterogeneity:the gram positive bacteria were the dominant microorganisms in all
soil samples. AM fungi, gram positive bacteria, gram negative bacteria and fungi
were all characterized by Alxa > Wuhai > Dengkou, and total PLFA content of
actinomycetes followed the order of Wuhai > Alxa > Dengkou. AM fungi occupied the
biggest proportion in the soil fungal biomass, especially in Dengkou and Alxa,
which accounted for 91% and 92%, respectively. We concluded that AM fungi were an
important component of soil microorganisms in the desert ecosystem. AM fungi,
gram positive bacteria, gram negative bacteria, fungi and actinomycetes were
positively correlated with soil acid and alkaline phosphatase, total glomalin,
ammonia nitrogen and pH. G+/G- were extremely negatively correlated with soil
urease, organic carbon and easily extractable glomalin. However, the
fungi/bacteria were extremely positively correlated to soil urease, organic
carbon and easily extractable glomalin. The results of this study support the
conclusion that soil acid and alkaline phosphatase, total glomalin, ammonia
nitrogen and pH were the main factors influencing soil microbial biomass and
activities in desert zone.Moreover, the changing pattern of soil microbial
community might be useful to monitor desertification and soil degradation.
PMID- 29964483
TI - [Response of Soil Respiration to Extreme Precipitation in Semi-arid Regions].
AB - Evaluating the response of soil microbial respiration to extreme precipitation
event is significant for a better understanding about the influence of the change
of precipitation regime on soil carbon cycling under global warming. A simulated
experiment of extreme precipitations was conducted during the rainy season (July
September 2015) in the Changwu State Key Agro-Ecological Station, Shaanxi, China.
The treatments consisted of three total precipitations in rainy season (600 mm,
300 mm, and 150 mm) and two precipitation regimes (10 mm, 150 mm; P10, P150).
Soil microbial respiration varied differently in the same single rainfall event
among three precipitations. The variation coefficient of soil microbial
respiration under 600 mm total precipitation was 36% (P150) and 33% (P10), and
28% and 22% under 300 mm total precipitation, 43% and 29% under 150 mm total
precipitation. Under 600 mm total precipitation, the cumulative soil microbial
respiration under P150 was 20% less than that under P10; however, the cumulative
soil respiration of P150 under 150 mm total precipitation was 22% more than that
under P10; and there was no significant difference between P10 and P150 under 300
mm total precipitation. Therefore, the duration in soil water stress must be
considered to estimate soil microbial respirations under extreme precipitations.
PMID- 29964484
TI - [Features and Influencing Factors of N2O Emissions from Drawdown Area in the
Three Gorges Reservoir].
AB - Three heights (180 m, 175 m and 155 m) located in a typical drawdown area in
Wangjiagou of the Three Gorges Reservoir were selected for studying the N2O
emissions from subtropical reservoirs. The experimental period lasted two years
from August 2010 to August 2012. The methods of static opaque chambers during the
drainage period and floating chambers during flooding period were adopted in this
study. The heights of 175 m and 155 m were both located in the drawdown area,
whereas the 180 m height was located in the land as a control to 175 m and 155 m.
N2O fluxes showed clear seasonal trends at each height and remarkable differences
were observed between the two years at the 180 m height. N2O fluxes were lowest
in spring at the 180 m height. N2O fluxes showed a single-peak pattern with
climax in summer in the first year, whereas a double-peak pattern with climax in
summer and after dry-wet alternating in the next year after the highest water
level of 175 m was succeeded in the Three Gorges Reservoir. N2O fluxes presented
a single-peak shape with summer climax at the 155 m height. Additionally, N2O
fluxes were higher during the drainage period than in the flooding period at both
the 175 m and 155 m heights. The order of the annual N2O cumulative emissions at
the three heights was 175 m (853.92 mg.m-2) > 180 m (336.69 mg.m-2) > 155 m
(324.69 mg.m-2), and there was a notable difference between 175 m and 155 m,
indicating that short-term flooding could increase N2O emissions but long-term
flooding could restrain N2O emissions. Correlation analysis showed that there
were no obvious relativities between N2O fluxes and environmental factors in the
land and during the drainage period. However, N2O fluxes were significantly
negatively correlated with water temperature and wind speed during the flooding
period. Principal component analysis found that soil nutrient conditions and
physicochemical properties were the most important factors for N2O emissions in
the land, the nitrogen distribution in water was a main determinant for N2O
emissions during the flooding period, and soil physicochemical properties and
microbial activity importantly affected N2O emissions during the drainage period
in the drawdown area.
PMID- 29964485
TI - [Denitrification Loss and N2O Emission from Different Carbon Inputs in Orchard
Drains Sediments].
AB - The orchard is an important economic crop in Taihu Lake region. Heavy nitrogen
application in orchard results in great nitrogen loss to drainage ditch, and
unbalanced carbon nitrogen ratio. Therefore, carbon might be an important
limiting factor for sediment nitrification and denitrification. A soil incubation
experiment controlled by the acetylene inhibition method was conducted under
laboratory conditions to study the denitrification loss and N2O emissions of
orchard drainage ditch soil. We designed five carbon input levels of 0, 5, 25, 50
and 100 mg.L-1, which were noted as C0, C1, C2, C3 and C4, respectively,
meanwhile there was 5 mg.L-1 net nitrogen input in the form of KNO3 in each
treatment. The results showed that carbon inputs could stimulate both
denitrification rates (DN) and N2O emission rates. Carbon and nitrogen ratio had
a significant effect on N2O emission rates and denitrification loss rates
(P<0.05). When the carbon and nitrogen ratio was 10:1, total cumulative
denitrification losses and N2O emissions were both highest (319.26 MUg.kg-1 and
6.20 MUg.kg-1, respectively) among the treatments, which accounted for 1.28% and
0.02% of net nitrogen input, respectively. This result indicated that the carbon
and nitrogen ratio of 10:1 was most favorable for N2O emissions and
denitrification process in sediments.
PMID- 29964486
TI - [Emissions Characteristics of Greenhouse Gas from Sewage Sludge Composting
Process in Winter].
AB - Sludge composting is an efficient way to realize the reclamation of waste sludge,
while the Green House Gas (GHG) accompanying with it has raised great concern
worldwide. However, we do lack the primary data in this area and a great
uncertainty of the effect and GHG emission characteristics of sludge composting
process in low-temperature environment also exists. This study is aiming to
investigate the emission characteristics of GHG from composting in low
temperature environment by applying two different bulking agents to dewatered
urban sludge. The results showed that aerobic composting could go smoothly even
in an environment with lower temperature, yet the maturity was low due to a sharp
drop of pile temperature at the stage of maturing. Sawdust treatment could reduce
the total nitrogen loss compared with cornstalk treatment, while its GHG emission
equivalence was higher (169.45 and 133.13 kg.t-1 dry sludge, respectively). The
accumulative CH4 emissions of sawdust and cornstalk were 0.648 and 0.689 kg.t-1
dry sludge, respectively, of which over 75% was from the first two weeks; total
N2O emissions of sawdust and cornstalk were 0.486 and 0.365 kg.t-1 dry sludge, of
which more than 90% came from the decomposting process. On the whole, because of
the relatively short duration of high temperature as well as the low temperature
during mature stage, the process had an especially low emission of CH4 but a
relatively high discharge of N2O. For composting in low-temperature environment,
necessary measures should be taken to control N2O emission in the late period in
order to realize GHG reduction.
PMID- 29964487
TI - [Distribution and Source Analysis of Polycyclic Aromatic Hydrocarbons (PAHs) and
Organochlorine Pesticides (OCPs) in Soils from Shergyla Mountain, Southeast
Tibetan Plateau].
AB - Soils were collected from Shergyla Mountain shade slope and south-facing slope in
southeast Tibetan Plateau (TP) in August 2012 and they were measured for
polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides
(OCPs)(including HCHs and DDTs). The concentrations of ?16PAHs ranged from 99.3
to 1984 ng.g-1 dw, with a mean value of 1017 ng.g-1 dw. HCHs and DDTs in soils
samples were in the range of 0.37-2.07 ng.g-1 dw (mean 1.15 ng.g-1 dw) and 0.70
43.9 ng.g-1 dw (mean 9.87 ng.g-1 dw), respectively. The concentrations of all
measured compounds were much higher than those in central or western TP,and the
PAHs concentration was even up to two orders of magnitude. The concentrations of
alpha-HCH and DDTs in south-facing slope increased with altitude, but HCHs and
DDTs in shade slope had no significant correlation with altitude. There was no
consistent increasing or decreasing trend of PAHs in shade slope with altitude,
and the concentrations of PAHs in south-facing slope showed a higher value in
lower altitude, indicating the existence of local pollution emissions. The PAHs
profile was dominated by lighter constituents (2 & 3-ring accounted for higher
than 85%),inferring that the PAHs in the study area were largely influenced by
long range atmospheric transport (LRAT) of pollutants. The special diagnostic
ratios of PAHs suggested that PAHs were mainly produced by low temperature
combustion of biomass and fossil fuels, except that two sampling sites of shade
slope had been possibly influenced by oil residue. The relatively low ratios of
alpha/gamma-HCH inferred HCHs in the research area was the result of the combined
contribution of the historical technical HCHs and Lindan. The ratios of p,p'
DDE/p,p'-DDT and o,p'-DDT/p,p'-DDT indicated DDTs were from the combined
contribution of the historical technical DDTs and dicofol. According to the
profile of PAHs, HCHs and DDTs and the meteorological conditions of Shergyla
Mountain, the transport of PAHs and OCPs in the study area was mainly influenced
by the Indian Monsoon.
PMID- 29964488
TI - [Applications of Geostatistical Analyses and Stochastic Models to Identify
Sources of Soil Heavy Metals in Wuqing District, Tianjin,China].
AB - A survey on soil samples was conducted to study the heavy metal pollutions and
their potential sources in Wuqing District, Tianjin, China. A total of 578
topsoil samples were collected and the concentrations of eight heavy metals,
namely, Cd, Pb, Cu, Zn, Cr, Ni, As (metalloid) and Hg were analyzed. A summary of
descriptive statistics, principal component analysis, geostatistical analysis and
stochastic forest regression models were applied to study the spatial and
temporal variation and identify proportional contribution from either natural or
anthropogenic sources for the eight heavy metals in topsoils of the study region.
The results indicated that the average concentrations of all the heavy metals
except for Cr in the topsoils exceeded their corresponding natural-background
values. As, Ni and Cr were mainly contributed by natural sources (i.e., soil
parent materials). Cu and Zn originated from both the soil parent materials and
sewage irrigation. Pb and Cd originated mainly from non-point source pollution
and partially from point source. Hg originated from sewage irrigation. It was
proved that combination of multi-technologies provides an effective way to
delineate multiple heavy metal pollution sources.
PMID- 29964489
TI - [Effects of Soil Moisture and Temperature Variations on Organic Carbon
Mineralization of Purple Soil in the Hydro-fluctuation Belt of the Three Gorges
Reservoir].
AB - Soil sampling in the field and an incubation experiment in the laboratory was
conducted to investigate the effects of soil moisture and temperature on soil
organic carbon (SOC) mineralization of purple soil in the hydro-fluctuation belt
of the Three Gorges Reservoir. Three incubation temperatures (10, 20 and 30C) and
four moisture levels (40% water holding capacity (WHC), 70% WHC, 100% WHC and
submerged condition) were used in the experiment. In the entire incubation period
(66 d), the SOC cumulative mineralization reached the maximum at 100% WHC, but
there was no significant difference between 100% WHC and submerged condition
(P>0.05). At 10C and 20C, the SOC cumulative mineralization at 100% WHC and under
submerged condition was not significantly different from that at 70% WHC
treatment, but significantly higher than that at 40% WHC treatment. While the
cumulative mineralization of organic carbon at 100% WHC and under submerged
condition was significantly higher than that at 70% WHC and 40% WHC when the
temperature was 30C (P<0.05). The results indicated that compared with 70% WHC
treatment, the higher moisture content (100% WHC and submerged condition) had no
negative effects but rather promotion effects on the mineralization of SOC at
high temperature (30C). Under the same soil moisture conditions, the SOC
cumulative mineralization of purple soil in the hydro-fluctuation belt increased
as temperature increased. Moreover, the analysis of variance showed that SOC
cumulative mineralization was significantly affected by temperature and soil
moisture, and there was a significant interaction with temperature and soil
moisture (P<0.05). Fitting of two-pool first-order model was performed to
indicate that temperature and soil moisture influenced the contents of labile SOC
fraction and the mineralization rates of recalcitrant SOC fraction, which led to
the differences of SOC cumulative mineralization under the different treatments.
With the increasing temperature, the temperature sensitivity was significantly
decreased in the 40% WHC treatment, but there was no obvious difference when the
soil moisture content was not less than 70% WHC.
PMID- 29964490
TI - [Reduction Effect of Reduced Phosphorus Fertilizer and Combining Organic
Fertilizers on Phosphorus Loss of Purple Soil Sloping Field].
AB - In order to better understand the effect of reduced phosphorus fertilizer and
combining organic fertilizers on phosphorus loss of purple soil sloping field,
three rainfall-runoff events were monitored using field runoff observation method
in the purple soil sloping field in 2014. There were six treatments in this
research, including optimized fertilization (P), optimized fertilization+pig
manure application (MP), optimized fertilization+straw return (SP), optimized
fertilization which was reduced by 20%+pig manure application (MDP), optimized
fertilization which was reduced by 20%+straw return (SDP), without phosphate
(P0). The results indicated that the interflow was the main pathway of runoff for
purple soil sloping field. The average contents of total phosphorus (TP) and the
phosphorus loss load of overland flow were all much higher than those of the
interflow. The overland flow was the main pathway of the phosphorus loss load for
purple soil sloping field. Reduced phosphorus fertilizer and combining organic
fertilizers had a significant reduction effect on phosphorus loss of purple soil
sloping field. Compared with the treatment P, the average content of total
phosphorus on SDP was reduced by 57% and that on MDP was reduced by 48% in the
storm rainfall. Combining straw was better than pig manure. The average contents
of the phosphorus loss load of typical rainfall changed between 0.01 and 0.26
kg.hm-2. In different fertilization treatments, the average contents of the
phosphorus loss load followed the order of P > MP > SP > MDP > SDP > P0. Reduced
phosphorus fertilizer and combining organic fertilizers had a significant
reduction effect on phosphorus loss of overland flow, but increased soil
phosphorus leaching for purple soil sloping field.
PMID- 29964491
TI - [Transformation and Migration of Sulfur Speciation in the Rhizosphere and Bulk
Soil of Paddy Soil].
AB - A pool culture experiment was carried out to investigate the influence of
different forms of sulfur fertilizers (sulfur and gypsum) on the transformation
and migration of sulfur speciation in the rhizosphere and bulk soil of unpolluted
and polluted paddy soils.The results showed that the redox potential (Eh) was
about 93-283 mV and 83-254 mV, respectively, the soil solution pH was 7.5-8.4 and
7.7-8.4, respectively, and pe+pH was 9.1-13.2 and 9.1-12.5, respectively, in the
bulk and bulk soil.Solution Eh values in Rhizosphere soil were generally higher
than those in bulk soil, and solution pH in the former was generally lower than
that in the latter.The different forms of inorganic sulfur followed the order of
water-soluble sulfur (41%-81% of total inorganic sulfur, similarly
hereinafter)>>sulfur adsorption (9%-34%)>hydrochloric acid soluble sulfur (8%
24%)>hydrochloric acid volatile sulfide (2%-8%) in the rhizosphere.In tillering
and earing flowering,the concentrations of water-soluble and absorbed sulfur by
application of gypsum were significantly higher than those using elemental
sulfur.And its content in unpolluted paddy soil was significantly higher than
that in polluted paddy soil. In the bulk soil,the forms of inorganic sulfur
followed the order of water-soluble sulfur (40%-69%)>>hydrochloric acid soluble
sulfur (18%-41%)>hydrochloric acid volatile sulfide (6%-16%)>adsorbed sulfur
(0.7%-7.5%).The mass fractions of inorganic sulfur, organic sulphur and the total
sulfur in the rhizosphere soil were in the range of 223-738 mg.kg-1, 574-1647
mg.kg-1 and 825-2287 mg.kg-1,respectively,and the corresponding fractions were in
the range of 68-128 mg.kg-1, 108-391 mg.kg-1 and 200-477 mg.kg-1 in the bulk
soil,respectively.Inorganic sulfur and organic sulfur of total sulfur in the
rhizosphere were 20%-40% and 60%-80%, respectively, and those in the bulk were
18%-46% and 54%-82%, respectively.Total sulfur. organic sulfur and water-soluble
sulfur and adsorbed sulfur and hydrochloric acid soluble sulfur in the
rhizosphere were 3-11 times, 3-5 times, 5-7 times, 12-20 times, and 2-3 times of
those in the bulk soil, respectively, whereas the hydrochloric acid volatile
sulfur in the rhizosphere was lower than that in the bulk soil.
PMID- 29964492
TI - [Comparison of the Persistence of a Combined Amendment Stabilizing Pb, Cd, Cu and
Zn in Polluted Paddy Soil].
AB - A three-year in-situ experiment was conducted in a paddy soil near a mining area
in southern Hunan in order to study the persistence of combined amendment of
limestone+sepiolite (marked as LS) stabilizing Pb, Cd, Cu and Zn in polluted
paddy soil. LS with ratios of 0, 2, 4, and 8 g.kg-1 was applied once to the paddy
soil, and rice was subsequently planted for three consecutive years of 2012
(first season), 2013 (second season), and 2014 (third season). The experimental
results indicated that:1LS significantly increased soil pH values for all three
seasons, and the enhancement ranked as follows:first season > second season >
third season. 2 LS obviously decreased the exchangeable contents of soil Pb, Cd
and Zn for all three seasons, and the decreasing magnitude of exchangeable
contents of soil heavy metals was 32.6%-97.7% for Pb, 8.3%-71.4% for Cd, and
10.9%-83.5% for Zn, respectively, in the third season; however, there was no
significant decrease for Cu. The effects of LS decreasing exchangeable contents
of soil heavy metals in three seasons followed the order of Pb > Zn > Cd > Cu. 3
LS decreased contents of Pb and Cd in brown rice in the third season by 26.7%
66.7% and 59.1%-80.3%, respectively, and the reduction trend increased with
increasing LS application. Cu and Zn contents in brown rice did not decrease
effectively. The effect of LS reducing contents of Pb, Cd, Cu and Zn in brown
rice followed the order of Pb > Cd > Cu > Zn for the first season and the second
season, but Cd > Pb > Zn > Cu for the third season. For all three seasons, the
total effect of LS reducing heavy metal contents in brown rice followed the order
of Pb > Cd > Cu > Zn. 4 The effect of LS stabilizing soil Pb and Cd emerged
gradually with time. Therefore, LS was suitable for remedying soil polluted with
Pb and Cd for a relatively long time because of its persistence.
PMID- 29964493
TI - [Bio-inspired Recovery of Platinum Nanoparticle and Its Mechanism].
AB - This paper illustrated an approach of using a self-isolated bacterium
Enterococcus faecalis Z5(CCTCC M2012445) to recover platinum nanoparticles from
aqueous solution, and exploring its possibility under the condition of providing
an exogenous electron donor. At the same time, the impacts of initial Pt
concentration, biomass, temperature and pH on recovery process were researched to
explore the possible mechanism of recovery process. The results showed that
Enterococcus faecalis Z5 could recover platinum nanoparticles and there were two
steps:bio-sorption and bio-reduction. And the initial Pt concentration 286.46
mg.L-1, biomass 3.2 g.L-1, temperature 50C and pH 6 for biorecovering were
optimized. The TEM and XRD results indicated that the reduction products were
platinum nanoparticles, of which most were distributed on the periplasm and the
diameters were about 5 nm. Moreover, as shown by XPS figures, Pt (IV) was firstly
reduced to Pt (II), then further reduced to Pt (0) and nanoparticles were formed.
The reduction of Pt (II) to Pt (0) was a rate-limiting step. And the FTIR result
showed the corresponding peaks of hydroxyl and amide group changes on the
bacterium before and after reduction, probably playing an important role in the
reduction process.
PMID- 29964494
TI - [Preparation of gamma-Fe2O3 Catalyst by Heat Treatment of Natural Limonite for
Selective Catalytic Reduction of NO by NH3].
AB - Natural limonite was used as a precursor to prepare gamma-Fe2O3 via thermal
treatment. The influences of reaction temperature, manganese oxides existing in
limonite and coexisting SO2 and H2O on the catalytic reduction activity of the
preparedgamma-Fe2O3 were evaluated, and the activity of SCR was compared with
that of alpha-Fe2O3, by means of XRD, XRF, XPS, NH3-TPD, FT-IR and so on. The
results showed that because the surface acidity of gamma-Fe2O3 is stronger, the
SCR temperature window of gamma-Fe2O3 was 200-350C being broader than that of
alpha-Fe2O3 (200-300C), and in the active temperature window, the NO removal
reached over 99%. The existence of MnO2 in the newly formed gamma-Fe2O3 slightly
decreased the SCR reactivity at lower temperature (100-200C), while it decreased
the SCR reactivity at higher temperature (400-450C). The existence of SO2 led to
the shifting of temperature window by 100C from 200-350C to 300-450C, and the
volume fraction of 5%H2O only had a tiny negative effect on the SCR reactivity of
gamma-Fe2O3. However, the coexisting SO2 and H2O, especially when the volume
fraction of SO2 reached 0.12%, significantly decreased the SCR reactivity due to
the generation of ammonium sulfate. Besides, although the magnetic susceptibility
of reacted gamma-Fe2O3 experienced a slight decrease compared with the newly
prepared gamma-Fe2O3, the catalysts could still be used repeatedly by magnetic
recycling.
PMID- 29964495
TI - [Atmospheric Dry Deposition Fluxes and Seasonal Variations of Particulate Matter
and Lead in Urban Beijing].
AB - To investigate the dry deposition pattern of particulate matter and lead in urban
Beijing, dry deposited particles were collected based on a surrogate surface
between December 2013 and November 2014 and subjected to elemental analysis by
using microwave digestion and inductively coupled plasma mass spectrometry. The
results showed that dry deposition fluxes of particle mass and total lead were
0.84 t.(hm2.a)-1 and 7.56 mg.(m2.a)-1, respectively, with a seasonal trend of
spring > winter > autumn~summer, exhibiting a similar temporal pattern to that of
coarse particles. In addition, dry deposition flux of water-soluble lead was 3.14
mg.(m2.a)-1. It was found that the ratio of soluble fraction to total lead in dry
deposited particles reached up to 43%, coinciding with a seasonal variation of
ambient sulfur dioxide. The findings highlighted the anthropogenic imprints on
the dry deposition flux of particles and heavy metals as well as the solubility
of lead. This study also provides a first-hand dataset that can be used to assess
ecological and environmental impacts of dry deposited lead, and an up-to-date
scientific basis for the crafting abatement strategies to further reduce emission
of heavy metals in China.
PMID- 29964496
TI - [Pollution Characteristics of Heavy Metals in PM2.5 and Their Human Health Risks
Among the Coastal City Group Along Western Taiwan Straits Region, China].
AB - PM2.5 samples were collected from 11 sampling sites in the coastal city group
along western Taiwan Straits region, China, and these heavy metal elements (Zn,
Cu, Pb, Ni, Cr, As) were detected using particle-induced X-ray emission (PIXE)
method. The pollution characteristics, enrichment factors and source
apportionment of heavy metals in PM2.5 were analyzed, and furthermore, their
human health risks were determined. The result showed concentration distribution
was obviously different between PM2.5 and heavy metals in the city group, for the
main sources (e.g. construction dust and ground dust) for PM2.5 were not the main
contribution to these heavy metals. The enrichment factors of Zn, Cu, Pb, Mn, Ni,
Cr, As exceeded 10, which suggested these metals were enriched and significantly
impacted by anthropogenic pollution. Three main groups of heavy metals in PM2.5
were identified by principal component analysis (PCA-MLR), such as coal
combustion and traffic emissions (70.59%), multiple sources (coal and oil
combustion, pyrometallurgical process, 17.55%) and other industry (11.86%). The
risk levels for carcinogenic heavy metals (Ni, Cr, As) and non-carcinogenic heavy
metals (Zn, Cu, Pb, Mn) were lower than the average level of risk acceptance (10
6), which suggested these heavy metals did not cause harm to human health in
these cities.
PMID- 29964497
TI - [Correlation of Speciated Mercury with Carbonaceous Components in Atmospheric
PM2.5 in Shengsi Region].
AB - PM2.5 samples of four seasons were collected from Nov. 2014 to Aug. 2015 at the
site of Shengsi island in Zhoushan islands. Mercury (Hg) and speciated mercury
concentrations in PM2.5 samples were measured by Atomic Fluorescence Spectrometry
(AFS-9130, China) after digestion with CEM Mars Xpress (PyNN Corporation, USA).
The concentrations of organic carbon (OC) and elemental carbon (EC) in PM2.5
samples were determined by thermal/optical carbon analyzer (DRI, USA). The
results showed that the daily concentrations of PM2.5-bounded mercury (PBM)
ranged from 0.02 to 1.25 ng.m-3. Moreover, the mass content of PBM was (12.46+/
18.79) MUg.g-1, which was higher than those in continental cities. ANOVA analysis
result suggested that the highest average mass concentrations of PBM occurred in
fall, sequentially followed by spring, winter and summer. Higher concentrations
of PBM were in fall and spring, which might be related to biomass burning. In
addition, RPM took the highest fraction of 53.1% in PBM, followed by HPM (27.3%)
and EPM (19.7%), which might be resulted from the complicated composition of
marine aerosols. The strong correlations among OC, EC and PBM indicated that
carbonaceous composition may affect the transport of Hg in the atmosphere. The
ratio of OC/EC represents atmospheric photo-oxidation capacity, so the positive
correlation between OC/EC ratio and HPM indicated that HPM was resulted from
atmospheric gas-particle transformation. The negative correlation between Char
EC/soot-EC and mercury species indicated that the atmospheric particle-bounded
mercury might come mainly from the input of external mercury sources.
PMID- 29964498
TI - [Compositions and Sources of Summertime Dicarboxylic Acids and Related SOA in
PM2.5 from Mt. Taishan].
AB - To identify the compositions and sources of dicarboxylic acids and related SOA in
Mt. Taishan, PM2.5 samples were collected from July to August, 2004, and analyzed
for dicarboxylic acids and related compounds, the tracers of biogenic secondary
organic aerosol (SOA) (Isopene, alpha-/beta-Pinene and beta-caryophyllene SOA
tracers), water-soluble organic carbon (WSOC) and inorganic ions. The results
showed that total dicarboxylic acids were (376+/-189) ng.m-3, and C2 was the most
abundant dicarboxylic acid, followed by C3, C4 and C9. The concentrations of
diacids were more abundant than those in marine regions, but lower than those in
urban and other mountainous areas, indicating that the atmosphere in Mt. Taishan
was less influenced by anthropogenic pollution. C2/C4, C3/C4 and F/M ratios
indicated that diacids were mostly produced by more intensive photochemical
oxidation. The relative abundance of C9 to the total diacids, C9/C6 and C9/Ph
ratios were higher than those in urban, marine and mountainous regions, further
suggesting that SOA in Mt. Taishan atmosphere were mostly derived from biogenic
sources rather than anthropogenic sources. Compared to the budgets of model and
correlation analysis, it suggested that diacids and related SOA in Mt. Taishan
were mostly derived from photochemical oxidation of local biogenic sources.
PMID- 29964499
TI - [Variation Characteristics and Health Risk Assessment of BTEX in the Atmosphere
of Northern Suburb of Nanjing].
AB - BTEX concentrations were determined by GC5000 online gas chromatography in the
atmosphere of the north suburb of Nanjing in March 2013 to February 2014, using
the EPA human exposure analysis evaluation method for benzene series compounds of
volatile organic compounds (VOCs) in health risk assessment. The results showed
that the total amount of BTEX showed the variation characteristics of spring >
winter > autumn > summer. BTEX concentration was higher in the periods of 07:00
10:00 and 17:00-20:00, and the lowest was detected between 13:00-15:00; At the
weekend, the concentration of BTEX was higher than on the working day. The
sources of BTEX included traffic sources, industrial sources and solvent
evaporation. The HQ of BTEX in all four seasons showed the order of benzene >
xylene > ethylbenzene > toluene, and the HQ risk values were within the safety
range in all analysis periods. The distribution of R value was winter > autumn >
spring > summer, and R was higher than the safety threshold for all the analyses,
indicating the existence of carcinogenic risk.
PMID- 29964500
TI - [Inventory and Environmental Impact of VOCs Emission from Anthropogenic Source in
Chang-Zhu-Tan Region].
AB - Based on environmental statistical data and emission factor, an anthropogenic
volatile organic compounds (VOCs) emission inventory was established for the
Chang-Zhu-Tan region, and a grid with spatial resolution of 3 km*3 km was built
according to the spatial feature data. Ozone formation potential (OFP) and
secondary organic aerosol (SOA) formation potential of anthropogenic sources were
also estimated. The results showed that the total anthropogenic VOCs emission was
about 113.49 kt in Chang-Zhu-Tan region and the main sources were industrial
processes, solvent utilization and vehicles with the VOCs emission of 35.88 kt,
28.72 kt and 22.13 kt, respectively. Paving pitch and architecture wall painting
accounted for the majority of the solvent utilization and the building materials
industry accounted for 75.34% of VOCs emission from the industrial processes.
Liling was the largest contributor compared to the other cities in Chang-Zhu-Tan
region, where the VOCs emission from these anthropogenic sources in 2014 was
16.58 kt. The total OFP of these sources was 375.33 kt, in which solvent
utilization contributed 27.28% and the O3 generative capacity of biomass burning
was the largest. Solvent utilization contributed 35.35% to the total SOA
formation potentials and its SOA generative capacity was also the largest. The
spatial distribution characteristics revealed that the VOCs emission mostly
originated from urban area.
PMID- 29964501
TI - [Characteristics of Methane Emission from Urban Traffic in Nanjing].
AB - Urban traffic is an important source of greenhouse gases such as CH4. The
observations on CH4 are the basis for quantitative analysis of urban carbon
emissions. Taken into consideration the weekly and daily changing characteristics
of urban traffic, we conducted experiments to analyze the features of traffic
CH4emission and its influential factors. The experiments were conducted on 3 main
roads in Nanjing on Oct. 17, 18, 20, 23, 2014 with 5 periods of observation per
day, and in Nanjing Yangtze River tunnel in the morning and at night of Sep.11
2014. The results showed that:1 The average concentration of CH4 on the urban
main road of Nanjing city was greater than that of the background atmosphere.
Affected by traffic conditions, the spatial difference of DeltaCH4 concentration
was significant on three typical main roads. DeltaCH4 concentration's diurnal
variation showed inverted "W" type, and its peak appeared in the morning and
evening rush hours. 2 Due to the "piston wind" in the tunnel, the CH4
concentration in Nanjing Yangtze River tunnel gradually increased from the inlet
to the outlet and the difference of concentration between the inlet and the
outlet was 0.21*10-6-0.38*10-6. 3 There was a good linear correlation between CH4
concentration and CO2 concentration. The atmospheric DeltaCH4:DeltaCO2 value of
urban main road in Nanjing was 0.0091 and the atmospheric DeltaCH4:DeltaCO2 value
of Nanjing Yangtze River Tunnel was 0.00047-0.0014. 4 Traffic volume and the
proportion of natural gas vehicles were the main factors influencing atmospheric
DeltaCH4 concentration and DeltaCH4:DeltaCO2.
PMID- 29964502
TI - [Variations in Aerosol Optical Depth over Three Northeastern Provinces of China,
in 2003-2014].
AB - Based on the MODIS-Aqua aerosol optical depth (AOD) products from 2003 to 2014,
Nighttime Lights Time data from DMSP satellites and basic meteorological data,
the AOD spatial distributions of interannual and seasonal variations over three
northeastern provinces of China(Liaoning, Jilin, Heilongjiang) were analyzed. It
was found that there was a northeast-southwest area of high annual average AOD
composed of Dalian, Shenyang, Changchun, Harbin and other cities, the 12-year
average AOD value was 0.4-0.8. The low AOD occurred in the eastern and northern
areas of the three northeastern provinces of China, where the forest-covering
rate was high, and the 12-year average AOD value was less than 0.3. The seasonal
variations of annual average AOD showed an increasing trend from spring to
summer, then decreased in autumn and increased again in winter. The interannual
variations of AOD over three northeastern provinces of China showed a decreasing
trend in most areas, but the increasing trend occurred in the northeast-southwest
region with the axis formed by Shenyang, Changchun and Harbin, revealing the
polarization in recent 10 years over three northeastern provinces of China. In
addition, spatial distribution of annual average AOD over three northeastern
provinces of China in the years of strong and weak Western North Pacific Summer
Monsoon was studied. Affected by the surface wind field, annual average AOD in
weak monsoon years was higher than that in strong monsoon years.
PMID- 29964503
TI - [Variation Analysis of Daily PM2.5 Concentrations Based on Boosted Regression
Tree: A Case Study in Changzhou].
AB - Based on hourly concentration data from six state-controlled air quality
monitoring stations in urban area of Changzhou from December 2014 to November
2015, the seasonal variation of PM2.5 pollution was analyzed, and the
contributions of PM10, four kinds of gaseous pollutants and seven meteorological
factors to daily changes of rho(PM2.5) were quantified by boosted regression tree
(BRT). The results showed that:the seasonal differences of PM2.5 pollution were
significant, the pollution was serious in winter and the pollution duration was
long, while the pollution was light in summer. The spatial distribution of
rho(PM2.5) in four seasons was different, but the six monitoring stations showed
similar trends in each season. Daily average rho(PM2.5) was simulated and
verified by BRT. The correlation coefficient of the training data was 0.981, and
the cross-validation correlation coefficient was 0.957. In addition, the mean
deviation between the simulated values and the measured values was 1.80%, and the
standardized mean error was 10.41%, which showed that the model fitted well. The
contribution percentages of four kinds of impact types (PM10, gaseous pollutants,
meteorological factors and regional transport and diffusion) to daily average
rho(PM2.5) changes of four seasons were 23.4%, 28%, 36.2% and 12.6%,
respectively. So, the most significant affecting factor was meteorological
condition, followed by secondary formation, primary emission, and regional
transport and diffusion. In the factors with contribution percentages of more
than 5%, the daily average rho(PM2.5) was positively associated with PM10,
relative humidity, CO and O3, and was negatively correlated with temperature, SO2
and mixed layer high. In addition, the daily average rho(PM2.5) had complex
relationships with atmospheric pressure and NO2. For regional transport and
diffusion, the polluted air flow from southeast, west and north had a relatively
great negative impact on PM2.5 pollution of urban area in Changzhou.
PMID- 29964504
TI - [Characteristics of Mercury Emissions from Coal-fired Power Plants in Chongqing].
AB - Four typical coal-fired power plants in Chongqing, representing two different
boiler types (circulating fluidized bed boiler and pulverized coal boiler), were
chosen to investigate mercury emission characteristics through a mercury mass
balance method by analyzing mercury contents in all input and output raw
materials in order to accurately estimate mercury emissions. The results showed
coal with mercury concentrations ranging (80.77+/-6.39)-(266.83+/-4.71) MUg.kg-1
could be a significant contributor of input mercury in these four studied power
plants. Most mercury output from these power plants entered into solid waste with
high proportion of mercury entering the fly ash in CFB plants and entering the
fly ash and desulfurization gypsum in PC plants. Mercury removal efficiencies of
studied plants were in the range of 72.89%-96.05%, and these efficiencies in CFB
plants were higher than those in PC plants. The mercury emission factors for
EFelectricity and EFcoal of these four plants were 4.66-29.47 MUg.(kW.h)-1 and
8.55-71.77 mg.t-1, respectively. The mercury emission was also calculated to be
6.13-429.17 g.d-1. Mercury emissions from coal-fired power plants were associated
with the content of mercury in coal, boiler type, generation load, pollution
control equipment, and so on. To control the mercury emissions, more attention
should be paid to improving the generation load, increasing the mercury removal
efficiency of flue gas cleaning equipment, and strengthening the supervision of
solid waste re-utilization.
PMID- 29964505
TI - [Possible Sources of PCDD/Fs in Atmosphere of a Certain District in Guangdong].
AB - This paper analyzed 17 polychlorinated dibenzo-p-dioxins and
dibenzofurans(PCDD/Fs) by HRGC/HRMS in the flue gas of a certain municipal solid
waste incinerator(MSWI) and its surrounding air and other possible sources in
Guangdong. It discussed the feature of homologs and main toxic monomers in all
samples. It also investigated the relationship among surrounding area, MSWI and
possible sources using principle component analysis (PCA) and cluster analysis.
The results showed that the concentration of PCDD/Fs was higher in the flue gas
than the ambient air, moreover non-effect suffered by prevailing wind direction.
The possible sources might be tyre factory and open burning based on spot survey.
The concentration of PCDD/Fs was lower in tyre factory than upwind station, but
higher at open burning spot than outdrop monitoring station. The analysis of
homologs showed that OCDD, 1,2,3,4,6,7,8-HpCDD and 1,2,3,4,6,7,8-HpCDF were the
main materials in the flue gas and air, meanwhile OCDF was also found in
atmosphere. There was similar feature of 17 PCDD/Fs between surrounding
monitoring station and tyre factory, and the same between flue gas and open
burning. The further analysis showed that the linearly dependent coefficients of
1,2,3,7,8-PeCDD and 2,3,4,6,7,8-HxCDF were 0.95 and 0.75, respectively. It showed
the strong correlation of two monomers in all ambient air samples. The PCA and
cluster analysis showed that MSWI influenced the surrounding air, tyre factory
had an impact on upwind station, and open burning had a lower effect on outdrop
monitoring station.
PMID- 29964506
TI - [Sources and Pollution Characteristics of Antibiotic Resistance Genes and
Conditional Pathogenic Bacteria in Concentrated Poultry Feeding Operations].
AB - Concentrated animal feeding operations (CAFOs) is considered a source of airborne
human pathogens and antibiotic resistance genes. This study collected fecal
samples and corresponding air samples from inside and outside atmospheric
environments of layer and broiler feeding operations. We detected the types of 61
genes including five classes of antibiotics antibiotic resistance genes (23 genes
of ampicillin, 23 genes of tetracycline, 5 genes of quinolones, 5 genes of
sulfonamides and 2 genes of erythromycin), five conditional pathogenic bacteria
(Enterococcus, Escherichia coli, Staphylococcus, Campylobacter and Clostridium
perfringens) and class1 integron. Quantitative real time PCR was used to analyze
concentrations of typical genes with relatively high detection rates. The results
indicated that the detection rates of antibiotic resistance genes were 8,7,2,3
and 2. At the same time, two kinds of pathogenic bacteria were detected. The
detection rates of the target genes in the air were lower than those of the fecal
sample. The total bacterial gene (16S rDNA) concentration in the air of layer and
broiler was 106 copies.m-3, and that of the other typical genes was about
104copies.m-3. And the outdoor concentration was much lower than the indoor
concentration. The proportions of antibiotic resistance genes and conditional
pathogenic bacteria in the air were higher than those in the fecal samples and
the outdoor proportions were lower than the indoor proportions. Preliminary
results of this study indicated that feces was an important source of antibiotic
resistance genes, conditional pathogenic bacteria and class1 integron.
Aerosolization degrees of genes in feces were different. This study will provide
the basic data for both source tracking of antibiotic resistance genes and
pathogens from CAFOs and risk assessment of pollution of CAFOs in the surrounding
air environment.
PMID- 29964507
TI - [Distribution and Burial Characteristics of Nitrogen Forms in Sediment of Dianchi
Lake During Last Century].
AB - In order to analyze the composition, distribution and burial characteristics of
nitrogen in sediments of Dianchi Lake in the last hundred years, 6 sediment cores
were sampled in July 2014 to determine the contents of different nitrogen species
and sedimentary age sequence. The integrated results demonstrated a high content
of total nitrogen in sediments ranging from 1263.68-7155.17 mg.kg-1. The contents
of nitrate nitrogen and ammonium nitrogen were low, which were 10.00-144.00 mg.kg
1and 9.20-146.50 mg.kg-1, respectively. Organic nitrogen was the main component
in the sediments, ranging from 255.80 to 5644.25 mg.kg-1, composing a large
average percentage of 91.26%. In addition, the nitrogen pollution of sediment in
Dianchi Lake has reached a high level and is becoming serious since 1970s, which
surged in the late 1990s. The spatial difference of total nitrogen was obvious,
with comparably the most in the south, less in the north and least in the center.
The average deposition rate was changing from 0.092 g.(cm2.a)-1 to 0.187
g.(cm2.a)-1 in the last 100 years and increased first, then declined, finally
showed a slight upward trend over time. The burial rate of total nitrogen in
sediment increased over time and almost grew up straightly after 1990,which
decreased from the south to the north of Dianchi Lake in space. It was estimated
that the reserves of total nitrogen, organic nitrogen, nitrate nitrogen, ammonium
nitrogen in the sediment were 92139.15 t, 86745.62 t, 2464.16 t, 2929.37 t,
respectively, from 1900 to 2014.
PMID- 29964508
TI - [Temporal and Spatial Variations of Dissolved Inorganic Carbon and Its Stable
Isotopic Composition in the Surface Stream of Karst Groundwater Recharge].
AB - Stable carbon isotope of dissolved inorganic carbon (delta13CDIC), which is
mainly constituted by HCO3- in karst water, is widely used to trace the different
sources and influential factors of dissolved inorganic carbon (DIC). In order to
understand the distribution of DIC and delta13CDIC in subtropical karst area,
this paper researched the water chemistry and delta13CDIC in a karst surface
stream in detail, which is fed by Guancun subterranean stream in Liuzhou City,
Guangxi Province, in the southwest of China. The results showed that the contents
of DIC in subterranean stream outlet (G1 site) ranged from 4.60 to 4.90 mmol.L-1
with an average of 4.73 mmol.L-1 in dry season, and from 2.80 to 4.70 mmol.L-1
with an average of 4.23 mmol.L-1 in rainy season. The contents of DIC in 1.35 km
downstream site (G2 site) ranged from 4.30 to 4.90 mmol.L-1 with an average of
4.56 mmol.L-1 in dry season, and from 3.00 to 4.70 mmol.L-1 with an average of
4.20 mmol.L-1 in rainy season. The delta13CDIC of subterranean stream outlet (G1
site) varied from -12.80/00 to -11.530/00 with an average of -12.220/00 in dry
season, and from -13.120/00 to -11.010/00 with an average of -12.280/00 in rainy
season. The delta13CDIC of stream downstream site (G2 site) ranged from
11.710/00 to -9.550/00 with an average of -10.730/00 in dry season, and ranged
from -12.180/00 to -9.850/00 with an average of -11.100/00 in rainy season. The
contents of DIC of G1 site were higher than those of G2 site. The DIC contents in
dry season in both G1 and G2 site were higher than those in rainy season. The
values of delta13CDICof G1 and G2 site in dry season were more positive than
those in rainy season. The delta13CDICvalue of G1 site was more negative than
that of G2 site. The main sources of DIC in underground river and surface stream
were soil CO2and carbonate dissolution. However, the differences of DIC and
delta13CDICbetween G1 and G2 site showed that CO2degassing and photosynthesis of
aquatic plants had significant influence on water DIC and delta13CDIC value. This
study is helpful to understand the dynamic change and distribution of DIC and
delta13CDIC in karst surface stream.
PMID- 29964510
TI - [Response of the Water Quality of a Stratified Reservoir to an Extreme El Nino
Event During Summer].
AB - Global warming can intensify the El Nino phenomenon that recurs every 2-7 years,
which will lead to a great interannual variability of climate and may induce the
deterioration of the water quality of reservoirs. To study the influence of the
extreme El Nino events on the water quality of stratified reservoirs during
summer, field surveys were conducted in Zhoucun Reservoir and its inflow rivers
from May to August in a normal year (2012) and a strong El Nino year (2015).
Temporal variations of physical and chemical index were investigated during
monitoring. The results showed that the Zhoucun Reservoir was stratified during
the study period. The precipitation in the summer of the normal year was
significantly higher than that in the El Nino year at the same period. In the
summer of the normal year, the water level increased from 124.26 m to 127.14 m
and the hypolimnion thickness increased by 3.1 m. However, in 2015, the rapid
decrease of the water level from May to August (from 121.65 m to 119.46 m) led to
the decrease of the hypolimnion thickness (by 3.2 m). The inflow rivers belonged
to surface current and its nutrients concentrations were obviously higher than
those in the epilimnion. The inflow nutrients loads increased significantly in
the summer of the normal year, as a result, total nitrogen increased from 1.00
mg.L-1 to 2.06 mg.L-1, nitrate increased from 0.19 mg.L-1 to 1.28 mg.L-1, and
total phosphorus increased from 0.023 mg.L-1 to 0.088 mg.L-1 in the lacustrine
zone of the reservoir. In contrast, the nutrients concentrations changed little
in the summer of the El Nino year due to the decrease in runoff. Nonetheless, the
reducing pollutants concentrations of the hypolimnion in the El Nino year were
significantly higher than those in the normal year, which may be due to the
temporal variations of hypolimnion thicknesses. The maximum concentrations of
iron, manganese, ammonium and sulfide in the summer of the El Nino year were
0.38, 1.36, 2.36 and 1.67 mg.L-1, respectively. All these index exceeded the
standards for surface water Class III. We conclude that the extreme El Nino event
has an apparent influence on the nutrients concentrations in the epilimnion and
the pollutants concentrations in the hypolimnion in Zhoucun Reservoir.
PMID- 29964509
TI - [Succession Pattern of Phytoplankton of Daning River in the Three Gorges
Reservoir and Its Driving Factors].
AB - To elucidate succession pattern of phytoplankton in the Daning River and its
driving factors, multivariate statistical analysis was conducted. By using the
monitoring data in different seasons of Daning river during April 2012 to January
2013, this paper analyzed the succession pattern of phytoplankton in the Daning
River and its driving factors in typical tributaries of river-style reservoirs.
According to the characteristics of water level, the operational period of the
TGR was classified into following four stages:stage I (pre-November-April), stage
II (May-July), stage III (July-September) and stage IV (September-November). 1
The results indicated that the values of Chlorophyll-a concentrations and algal
density showed similar seasonal variations, with the highest values occurring in
stage III, followed by stages IV, II and I. Succession of C-R-S growth strategies
was the same generally:CR-R type dominated in stage I, CS, CR/CS and R-CR
dominated in stage II, III and IV, respectively. 2 The mean values of Margalef
index and Pielou index in stage IV and III were significantly greater than those
in stage II and I; the value of Shannon-waver index showed that the highest value
in stage III, followed in a descending order by stage I,II and IV; the
successional rate had the highest value in stage IV, followed in descending order
by stage III, I and II. 3 The results of Correlation analysis suggested that no
significant relationships were observed between the environmental parameters and
phytoplankton abundance in stage I. The results indicated that relative water
column stability(RWCS), index of feasible energy for phytoplankton (Et) and index
of feasible energy (Ef*) were key regulatory factors for phytoplankton community
in stage I. The results indicated that Et, Ef* and total phosphorus (TP) were key
regulatory factors for phytoplankton abundance in stage II. The results of the
redundancy analysis (RDA) suggested that RWCS, TP and the ratio of euphotic
depth[Deu(lambdaPAR)] to mixing depth (Dmix)[Deu(lambdaPAR)/Dmix] were key
regulatory factors for phytoplankton community composition in stage II. The
results indicated that Ef* and TP were key regulatory factors for phytoplankton
abundance in stage III. The results of the RDA suggested
that[Deu(lambdaPAR)/Dmix],Et, Ef* and TP were key regulatory factors for
phytoplankton community composition in stage III. The results indicated that TP
was key regulatory factor for phytoplankton abundance in stage IV. The results of
the RDA suggested that[Deu(lambdaPAR)/Dmix] was key regulatory factor for
phytoplankton community composition in stage IV.
PMID- 29964511
TI - [Effect of Coupling Process of Wetting-Drying Cycles and Seasonal Temperature
Increasing on Sediment Nitrogen Minerization in the Water Level Fluctuating
Zone].
AB - To reveal the effect of coupling process of wetting-drying and seasonal
temperature on sediment nitrogen (N) minerization, surface sediment samples were
collected from the water level fluctuating zone(WLFZ) of Pengxi River crossing
two hydrological sections. The sediment samples were incubated under drying and
submerging conditions at the controlled temperature. The result showed that NO3-
N and sand% in the sediment of higher altitude of water level (170 m) were higher
than those in low altitudes (150 and 160 m), whereas contents of TN, NH4+-N and
clay% and silt% in low altitudes were much higher. Generally, Net N
mineralization rate and cumulation were lower in higher altitude of water level
during the drying period and submerging period. The ammonification rate decreased
rapidly at the initial stage of incubation (0-7 d), and then had no obvious
change, and no significant differences among altitudes was observed. The
nitrification rate at low altitude decreased with incubation time, while it had
only a little change at higher altitude; The nitrification contributed a higher
fraction of net N mineralization than ammonification. Net N mineralization rate
and its cumulation were significantly higher in the drying period than in the
submerging period, while net N mineralization rate decreased with incubation time
at all altitudes. Net N mineralization cumulation tended to rise first and then
declined at all altitudes of the drying period, whereas it was continuously
decreasing at the low water level altitude during the submerging period. Net N
nitrogen mineralization rate of the drying period was positively correlate to
both the sediment organic matter content and its C:N ratio, while it showed a
negative correlation in the submerging period(P<0.001). Net N mineralization was
sensitive to temperature increase (Q10>1) in the drying period, while it was
insensitive during the submerging period of low altitude (Q10<1). Thus, the
impact of temperature on Net N mineralization was relatively low in submerging
period of winter and N was accumulated with low releasing rate. In contrast to
winter, summer exhibited warmer and drying period, this two factors would lead to
higher N mineralization rate and further induce the potential risk of
eutrophication as N releasing into water body.
PMID- 29964512
TI - [Photo-induced Phosphate Release from Organic Phosphorus Decomposition Driven by
Fe(III)-oxalate Complex in Lake Water].
AB - The phosphate released from organic phosphorus photo-decomposition has a
significantly influence on the phosphorus levels in the water column in lakes. In
order to reveal the effect of organic phosphorus photo-decomposition on phosphate
level in lake water, the phosphate released from organic phosphorus photo
decomposition driven by Fe(III)-oxalate complex under UV-Vis and sunlight
irradiation was investigated in natural lake water using glyphosate as the model
organic phosphorus. The effects of pH and initial concentration of Fe(III),
oxalate and glyphosate on the phosphate released from glyphosate photolysis were
studied. The results showed that phosphate could be released from glyphosate
degradation by Fe(III)-oxalate complex under UV-Vis and sunlight irradiation. The
concentration of phosphate reached 0.25 mg.L-1 and 0.18 mg.L-1 under UV-Vis and
sunlight irradiation for 60 and 720 min, respectively. The amount of phosphate
released increased with the increase of the initial concentration of Fe(III), as
well as the increasing oxalate and glyphosate concentration in lake water.
However, the increase of pH could significantly inhibit this process in the
reaction system. The concentration of phosphorus decreased with the addition of
isopropanol, which indicated that the hydroxyl radical (.OH) was one of the main
active oxygen species of Fe(III)-oxalate complex. The rates of.OH production for
Fe(III)-oxalate/UV-Vis and Fe(III)-oxalate/sunlight systems were 0.52*10-2
MUmol.(L.min)-1 and 0.03*10-2 MUmol.(L.min)-1, respectively. The steady-state
concentrations of hydroxyl radical (.OH) for the Fe(III)-oxalate/UV-Vis
conditions were 4.74*10-16 mol.L-1 and 0.27*10-16 mol.L-1 for the Fe(III)
oxalate/sunlight system.
PMID- 29964513
TI - [Preparation and Phosphorus Removal Mechanism of Highly Efficient Phosphorus
Adsorbent Mg/Al-LDO].
AB - Aiming at the problem of phosphorus removal in water, Mg/Al-layered double
hydroxides (Mg/Al-LDHs) were synthesized via optimized constant pH co
precipitation method, and highly efficient phosphorus adsorbent Mg/Al-layered
double oxide(Mg/Al-LDO) was obtained when it was calcined at high temperature.
Based on the adsorption characteristics of phosphorus removal, the study combined
Zeta potential, X-ray diffraction (XRD) and Fourier transform infrared
spectroscopy (FTIR) to analyze the changes of isoelectric point, crystal
structure and functional group before and after adsorption. In addition, Mg/Al
LDO of phosphorus adsorption mechanism was discussed. The results indicated that
using the optimized co-precipitation method in the conditions of Mg/Al=2:1,
calcination temperature 450C, and calcination time 2 h, the Mg/Al-LDO adsorption
capacity of phosphate was the best, and the maximum adsorption capacity could
reach 176.94 mg.g-1, which was basically consistent with the theoretical
adsorption capacity of 191.57 mg.g-1, far higher than those of Mg/Al-LDHs and
other phosphorus adsorbents. The results showed that the experimental data has
the best fitting result with pseudo-second-order kinetics model. The adsorption
process was consistent with Langmuir adsorption isotherm model. The results of
Zeta potential, XRD and FTIR showed that phosphorus adsorption of Mg/Al-LDO was
accomplished co-operatively by electrostatic attraction, anion in layer, ions
exchange, and surface co-ordination.
PMID- 29964514
TI - [Efficiency and Mechanism of Nitrogen and Phosphorus Removal in Modified Zeolite
Wetland].
AB - To study the efficiency and mechanism of nitrogen and phosphorus removal for
decentralized rural sewage in modified zeolite wetland, the modified zeolite was
applied as substrate into a combined process composed of anaerobic baffled
reactor (ABR) and baffled flow constructed wetland (BFCW), providing a new way
for rural sewage treatment in Suzhou City. The study was contrasted with zeolite
wetland. The results showed that the modified zeolite wetland had high efficiency
and stability of nitrogen and phosphorus removal, and the nitrogen and phosphorus
removal quantities of modified zeolite wetland were 1.8% and 1 times higher than
those of zeolite wetland during the trial. The modified zeolite wetland mainly
removed nitrogen and phosphorus by substrate adsorption, and the main fractions
of modified zeolite were Ca-P and Al-P. The oxygen-secretion and absorption of
plants stabilized the water quality of the effluent. The substrate adsorption was
the main nitrification removal pathway in front of the wetland, and nitrification
and denitrification were the main nitrification removal pathways at the end of
the wetland. The nitrogen and phosphorus adsorption capacities during the pilot
test were much higher than those of the static test. The optimization of
phosphorus adsorption capacity for modified zeolite was achieved under the
synergy of multiple pathways. The effect of configuration and plant root was the
main reason for the difference of nitrogen and phosphorus adsorption quantities.
Nitrification intensity led to the seasonal fluctuation of nitrogen removal
effect and stability in modified zeolite wetland, and the low nitrification
intensity in the front of wetland was related to the strong adsorption of NH4+-N
by the modified zeolite.
PMID- 29964515
TI - [Repression of Nitrogen and Phosphorus Release from Lakeshore Sediment by Five
Littoral-zone Plants].
AB - The article researched the effect of Iris pseudacorus L.,Paspalum distichum
L.,Leersia hexandra Swartz,Ludwigia peploides and Hydrocotyle vulgaris on the
nitrogen and phosphorus repression in sandy soil from lower reaches of Yangtze
River and clay from stored littoral zone. The result indicated that plants had a
significant inhibitory effect on total phosphorus release from sediment, with
concentration in overlaying water below 0.02 mg.L-1 in Paspalum distichum L.,
Hydrocotyle vulgaris, Iris pseudacorus group, below 0.03 mg.L-1 in Leersia
hexandra Swartz, Ludwigia peploides group; with release rate below 0.1 d-1 in
Leersia hexandra Swartz and Ludwigia peploides group, below 0.05 d-1 in Paspalum
distichum L., Hydrocotyle vulgaris, Iris pseudacorus group. While the plants were
proved to aggravate total nitrogen release by accumulating in sediment, with
concentration in overlaying water below 0.4 mg.L-1 in Paspalum distichum and Iris
pseudacorus L. group; with release rate below 0.02 mg.L-1. Root weight density,
root length density, root surface area density were major factors, which
increased the proportion of particles in sediment with diameter of below 50 MUm,
therefore decreased sediment resuspension against hydraulic disturbance; the root
system also enriched total nitrogen in sediment and absorbed phosphorus from
sediment. These five kinds of plants in terrestrial-aquatic transverse actually
repressed nitrogen and phosphorus release from sediment in two ways mentioned
above, Paspalum distichum L. and Iris pseudacorus L. possessed the best effect
due to their developed root system, followed by Leersia hexandra Swartz and
Hydrocotyle vulgaris, and Ludwigia peploides had the least effect.
PMID- 29964516
TI - [Simulated Desorption Kinetics of Lead by the Dominant Plant Roots Released Low
Molecular Weight Organic Acids from the Water-Level-Fluctuating Zone in the Three
Gorges Reservoir].
AB - Vegetations grow vigorously in the water-level-fluctuating zone (WLFZ) of Three
Gorges Reservoir (TGR) during the non-flooded period. Low molecular weight
organic acids (LMWOAs) excreted from the roots of these plants may active the
heavy metals in soil. In order to investigate the desorption kinetics of Pb in
the vegetation covered soil of TGR, the LMWOAs released from Cynodon dactylon and
Echinochloa crusgalli roots, which are the dominant species in WLFZ, were
analyzed both qualitatively and quantitatively. Furthermore, single and mixed
species of LMWOAs were also used in the simulation. The results showed that the
variety and content of LMWOAs secreted from Cynodon dactylon roots were larger
and higher than those of Echinochloa crusgalli. Citric acid, malonic acid, acetic
acid and malic acid were the same LMWOAs released from the two types of plants.
The contents of acetic acid were the highest among all LMWOAs, which were 0.765
and 0.261 mmol.kg-1 in Cynodon dactylon and Echinochloa crusgalli roots,
respectively.Citric acid, malonic acid and acetic acid were the same LMWOAs
detected from their rhizosphere soils. In the citric acid, malonic acid and
acetic acid desorption test, the desorption captivities of Pb were inhibited when
the concentration of LMWOAs was lower than 1 mmol.L-1. The desorption ability
displayed a decreasing order of malonic acid > citric acid > acetic acid.
However, the three LMWOAs promoted the desorption of Pb in soil when their
concentrations were higher than 1 mmol.L-1, respectively. The desorption ability
displayed a decreasing order of citric acid > malonic acid > acetic acid. During
the entire process of desorption, 0-240 min was the fast reaction stage, and the
remaining time was the slow reaction stage. The pseudo-second order kinetics
equation could fit best for the kinetic process.
PMID- 29964517
TI - [Experimental Research of Hg2+Removal by TiO2/Bentonite Composite].
AB - The TiO2/bentonite composite was synthesized by modifying calcium-based bentonite
with Nano-TiO2. The products before and after modification were characterized via
the approach of X-ray power diffraction(XRD) and scanning electron
microscope(SEM).The effect of TiO2/bentonite composite on mercury removal from
aqueous solutions of HgCl2was studied at different dosage, pH, adsorption time
and the initial concentration of Hg2+ was investigated and compared with the
bentonite by indoor simulation experiment, as well as the orthogonal experiments
to determine the optimal condition of Hg2+ adsorption. The experimental results
showed:after modified by TiO2, TiO2/bentonite composite particles were apparently
smaller, the basal spacing was increased and with a loose and porous structure.
The adsorption rates of TiO2/bentonite composite on Hg2+ were increased compared
with bentonite. The Hg2+ adsorption rates were increased with the increasing
dosages, pH and adsorption time. The adsorption rates were higher than 98.0% when
the dosage was 1.5 g.L-1, pH 7.0, and the adsorption time was 120 min. The
adsorption rates became smaller with increasing initial concentration of Hg2+.
False secondary dynamic equation could describe the adsorption of TiO2/bentonite
composite on Hg2+, and the chemical adsorption was dominant. The adsorption
isotherm of Hg2+ conformed to Langmuir equation, indicating that the adsorption
of Hg2+ was typical monolayer adsorption. The optimal experimental condition
was:dosage of 2.0 g.L-1, pH 8.0, adsorption time of 16 h and the initial
Hg2+concentration of 45 mg.L-1. Under this condition, the adsorption rate was
99.9%, and the equilibrium concentration of Hg2+ was 0.034 mg.L-1.
PMID- 29964518
TI - [Impact of Ammonia and H2O2 on Bromate and Disinfection By-products Control].
AB - A pilot-scale study with conventional water treatment and ozone-biological
activated carbon (O3-BAC) treatment was conducted to evaluate the impact of
ammonia and hydrogen peroxide (H2O2) addition on the bromate and disinfection by
products formation potential (DBPFP) control, with bromide containing water as
raw water. It was found that bromate concentration would exceed 10.00 MUg.L-1 as
ozone doses were higher than 1.0 mg.L-1 under different water qualities. Ammonia
and H2O2could effectively control bromate formation and bromate concentration
decreased as ammonia and H2O2 doses increased. Bromate concentration could be
controlled below 10.00 MUg.L-1 as ammonia dose was 0.10-0.30 mg.L-1 or the
m(H2O2)/m(O3) was 0.2-1.0. However, as ammonia-H2O2 was combined for the same
purpose, bromate increased firstly and then decreased. Ammonia addition would not
significantly affect the THMFP control but H2O2 application would depress the
efficiency of THMFP removal.
PMID- 29964519
TI - [Influencing Factors of Bacterial Activity in Water Distribution Networks].
AB - In order to study the variation patterns of bacterial activity in water
distributed networks, this paper studied a simulated water distribution network
in a northern China city. Microscopic examination and bacterial counts were
conducted on acridine orange-stained bacteria using fluorenscence microscopy to
ensure precise quantitative analysis. The ratio of viable bacterial count to
total bacterial count was used to characterize the overall bacterial activity in
the drinking water distribution network,as well as to study the impacts imposed
by various factors. As indicated, this method was proved to be rapid,reliable and
repeatable in bacterial counts. Populations of viable bacteria and total bacteria
in water samples were 103-104 cells.mL-1 and 104-105 cells.mL-1, respectively.
There was a positive correlation between the bacterial activity and water
temperature, turbidity, and flow velocity. There was also a negative correlation
between bacterial activity and residual chlorine after the operation stabilized.
The capacity of different forms of bacteria in the simulated water distribution
networks with tolerance of sodium hypochlorite was in the following order:long
rod-shaped, spherical-shaped, short-rod-shaped, and curved-shaped. The
reactivation and reproduction capability of rod-shaped bacteria was stronger.
There were more short-rod-shaped bacteria in summer water samples than in winter.
PMID- 29964520
TI - [Adsorptive Remediation of Cr(VI) Contaminated Groundwater with Chemically
Synthesized Schwertmannite].
AB - Schwertmannite is usually naturally found in acidic mining wastewater and
frequently used in the adsorption of heavy metal anions from water and
wastewater. Schwertmannite was synthesized through a facile chemical method and
utilized to remove Cr(VI) from contaminated groundwater. The kinetics,
thermodynamics and isotherms, as well as the effects of environmental factors on
the Schwertmannite adsorption processes were investigated. The experimental
results showed that the synthesized Schwertmannite had a strong adsorption
capability of Cr(VI) from aqueous solution. At the pre-set initial concentrations
of Cr(VI), the Schwertmannite adsorption of Cr(VI) achieved equilibrium within 24
h, and the Lagergren's second-order model fitted the adsorption process better
compared to Lagergren's first-order model and intraparticle diffusion model.
Langmiur equation fitted the adsorption isotherms better than Freundlich
equation. The Cr(VI) adsorption on Schwertmannite mainly involved ion exchange
reaction between Cr(VI) and anions such as OH- and SO42- and surface complexation
reactions. The DeltaHtheta and DeltaGtheta were 6.368 kJ.mol-1 and -1.215 kJ.mol
1, respectively, therefore the adsorption of Cr(VI) was a spontaneous and
endothermic process. The removal of Cr(VI) from aqueous solution increased with
increasing Schwertmannite dosage at pH=4.5. Acidic pH in the range of 4.5-6
favored Cr(VI) removal with Schwertmannite compared to that under basic
conditions. Under the conditions of 5 mg.L-1of initial Cr(VI) concentration, 0.5
g.L-1 of Schwertmannite dosage, pH=6, maximum Cr(VI) removal of 93.1% was
achieved and the adsorption capacity of Cr(VI) with Schwertmannite reached up to
40.4 mg.g-1. Batch tests showed that the presence of HCO3- and SO42- inhibited
the adsorption of Cr(VI) while Cl- had no significant impact. Cations and natural
organic matter had a pH-dependent impact on Cr(VI) removal:at pH=8 natural
organic matter and cations would significantly inhibit the Cr(VI) sorption, while
the impact could be neglected at weak acidic conditions (pH=6).
PMID- 29964521
TI - [Characteristics and Mechanism of Hybrid Ozonation-Coagulation Process in
Wastewater Reclamation].
AB - Because of the limited dissolved organic matter removal efficiency in
conventional pre-ozonation-coagulation process, the hybrid ozonation-coagulation
(HOC) process was developed for wastewater reclamation in this study. In this
process, coagulation and ozonation could synchronize within a single unit.
Compared with the pre-ozonation-coagulation process and traditional coagulation
process at the same coagulants dosage, the HOC process exhibited higher treatment
efficiency, especially better organic matter removal performance at each pH
value, which were 37.96% and 39.66%, respectively. In order to obtain the removal
mechanism of dissolved organic matters by HOC process,ozone decomposition at two
pH values either with or without AlCl3.6H2O was monitored in this study. The
results showed that higher pH and the addition of coagulant could accelerate
ozone decay. In addition, para-chlorobenzoic acid (p-CBA) was chosen as the
hydroxyl radical (.OH) probe compound to indirectly calculate the .OH exposure.
The results revealed that the HOC process was involved in .OH reaction and
coagulant could promote ozone decomposition due to its enhancing effect on .OH
production during the ozonation process. Furthermore, the ozone depletion
occurred more quickly at high pH due to its reaction with hydroxide ions (OH-),
leading to the formation of .OH through a series of chain reactions. Moreover,
the effects of tert-butanol, a well-known .OH inhibitor on ozone decay and p-CBA
decomposition were also investigated. The results indicated that ozone depletion
and p-CBA decomposition were significantly inhibited by tert-butanol, which
further proved that ozone was decomposed into .OH radicals through chain
reactions. In the HOC process, Al-based coagulants and hydrolyzed products could
act as catalysts to enhance ozone decomposition into .OH which is a powerful
oxidant to improve the organics removal efficiency.
PMID- 29964522
TI - [Nitrogen Removal Effect and Conversion Characteristics of Nitrous Oxide in
Single-stage and Multi-stage A/O Processes].
AB - The single-stage A/O and multi-stage A/O processes were simulated by sequencing
batch reactors (SBRs) with alternate stirring and aeration. The removal
efficiency of nitrogen and the release mechanism of N2O were studied under the
identical conditions of influent quality, hydraulic retention time (HRT), sludge
retention time(SRT), temperature and anoxic/oxic (A/O) retention time ratio.
Experimental results showed that COD or ammonia-nitrogen removal had no
significant difference between the single-stage and the multi-stage A/O processes
for the influent quality equivalent to municipal wastewater. However, TN removal
efficiency of the former was better than the later with 72.1% and 52.2%,
respectively. In the conversion of total nitrogen, during the typical cycle in
the single-stage A/O and multi-stage A/O processes, the yields of N2O were 16.95
mg and 3.95 mg, respectively. The conversion rate, which is the ratio of N2O
yield and TN removal, was respectively 11.47% and 4.11%. N2O production and
emission occurred mainly in aerobic (nitrification) phase while there was little
N2O emission in anoxic (denitrification) phase. Although the dominant species of
AOB was both Nitrosomonas in the single-stage A/O and the multi-stage A/O
processes under the same operating conditions, it was more conducive to the
growth of nitrifying bacteria (AOB, NOB) in the single-stage A/O process with the
greater abundance of Nitrosomonas. Meanwhile, the type and abundance of NOB in
the single-stage A/O process were significantly more than in the multi-stage A/O
process too. Therefore, it is more competitive to deal with the high
strengthening ammonia-nitrogen wastewater in the single-stage A/O process. In the
actual operation of wastewater treatment, using appropriate partitions of A/O or
oxygen-supplying modes can not only result in better nitrogen removal but also
decrease the secondary pollution caused by N2O to the atmosphere.
PMID- 29964523
TI - [Nitrogen Removal Performance of ANAMMOX with Different Organic Carbon Sources].
AB - Anaerobic ammonium oxidation (ANAMMOX) has been regarded as an efficient process
to treat high-strength wastewater without organic carbon source. To investigate
the nitrogen removal performance of ANAMMOX in the presence of organic carbon
source can broaden its application in organic wastewater treatment. In this work,
an anaerobic sequencing batch reactor (ASBR) was used to study the effect of
organic carbon source on ANAMMOX process. The experimental results indicated that
the activity of anaerobic ammonia oxidizing bacteria (AAOB) decreased by 84.2%
when 200 mg.L-1 COD of glucose was added. When sodium acetate was added, the
activity of AAOB was affected little. Besides, it even promoted the activity with
COD less than 120 mg.L-1. The effect of sucrose on ANAMMOX process was similar to
that of sodium acetate and the maximum specific ANAMMOX activity (SAA) increased
by 25.0% with 80 mg.L-1 COD. When citric acid was added, the maximum SAA peaked
with 80 mg.L-1 COD. The order of ANAMMOX promotion resulted from organic carbon
source was sucrose, sodium acetate, citric acid and glucose. With addition of
organic carbon source, nitrate could also be removed through the synergy of
ANAMMOX and denitrification, and the total nitrogen removal efficiency increased.
PMID- 29964524
TI - [Operational Performance and Microbial Community Structure in a Completely Mixed
Aeration System].
AB - A completely mixed aeration system was introduced in domestic sewage treatment,
and the simultaneous nitrification and denitrification process and microbial
community structure were further investigated. The pilot-scale experimental
results showed that the operation of the system was stable and the average
chemical oxygen demand (COD), NH4+-N and total nitrogen (TN) removal were 93.2%,
96.9% and 75.2%, respectively. The effluent COD, NH4+-N and TN were better than
the standard of level A stipulated by Discharge Standard of Pollutants for
Municipal Wastewater Treatment Plant (GB 18918-2002) in the absence of external
carbon source. The sludge derived from the system showed a significant
denitrification capacity and the denitrification rate was 2.86 times higher than
that in the wastewater treatment plant. In addition, the existence of aerobic
denitrifying bacteria in the system was confirmed by the PCR amplification of
genes encoding perplasmic nitrate reductases. The high-throughput sequencing
results revealed that Zoogloea, Thauera and Dechloromonas were dominant in the
completely mixed aeration system.
PMID- 29964525
TI - [Start-up of Combined Floc-granule CANON Process and the Effects of SRT on
Reactor Performance].
AB - To shorten the start-up time of CANON process and guide the sludge dischargement
in the practical project, the start-up of CANNON process and influence of
different flocs SRT were studied by inoculation ANAMMOX granules of different
proportions in two same specifications of SBR reactor. During the experiment, the
temperature was controlled at 30C+/-1C and pH was 7-8. The results showed that it
was not good for CANON process rapid start-up when the two reactors were
inoculated with 5% and 10% ANAMMOX granules respectively and the initial FA
concentration exceeded 44 mg.L-1. When the two reactors were inoculated with 5%
and 10% ANAMMOX granular sludge, the reactors were started-up successfully on Day
46 and Day 35, respectively. When the flocs SRT was maintained at 30 d, 90 d and
un-initiative discharge respectively, the average total nitrogen removal rate
could reach 0.35 kg.(m3.d)-1 stably. The quantitative PCR results of the three
different flocs SRT showed that with increasing flocs SRT, the abundance of AOB
was relatively stable, the abundance of ANAMMOX increased slightly, while the
abundance of NOB significant increased. Therefore, it is necessary to elutriate
flocs from reactor for decreasing the quantity of NOB and long-term stable
operation of the CANON process.
PMID- 29964526
TI - [Effects of Free Ammonia Regulation on the Performance of High Solid Anaerobic
Digesters with Dewatered Sludge].
AB - High free ammonia nitrogen (FAN) is regarded as a main factor that inhibits
biogas production in high solid anaerobic digestion systems with dewatered
sludge. Two mesophilic semi-continuous anaerobic digesters fed with dewatered
sludge (input total solids=15%) were operated and their performance under
different FAN concentrations by two regulation methods including pH reduction and
total ammonia nitrogen (TAN) promotion were investigated. Results showed that
when FAN was elevated from (400+/-174) mg.L-1 to (526+/-25) mg.L-1 with the
increase of TAN, the daily biogas yield declined from (11.9+/-0.3) L.d-1 to
(10.3+/-0.2) L.d-1. Meanwhile, volatile solids (VS) reduction rate decreased by
33.7%. When FAN dropped from (330+/-99) mg.L-1 to (47+/-13) mg.L-1 due to pH
reduction, daily biogas yield declined from (14.4+/-1.1) L.d-1 to (10.8+/-0.3)
L.d-1 and VS reduction rate decreased by 26.9%. The system performance was not
enhanced with the reduction of FAN. With the stop of pH regulation, FAN gradually
raised again to 300 mg.L-1 and digester performance recovered to the same as the
situation before regulation. The result suggested that inhibition occurred during
pH reduction. By 16S rRNA pyrosequencing analysis on bacterial and archaeal
diversity and quantitative PCR analysis aiming at methanogens, it was found that
bacterial community structure both changed obviously with obvious performance
decline in the two digesters. Excessive FAN (>500 mg.L-1) could change the main
bacteria species which degrade protein from Tepidimicrobium and Proteiniborus to
Anaerobranca. On the other hand, some carbohydrate and protein degrading bacteria
were also inhibited by pH reduction for FAN control, leading to the decline of
hydrolysis rates of organic matters. As a result, the shortage of substrate
supply for the methanogens weakened the biogas production of the digestion
system.
PMID- 29964527
TI - [Highly Efficient Bioflocculation of Microalgae Using Mucor circinelloides].
AB - Harvesting of microalgae is the major challenge in cost-efficient large-scale
microalgal biomass production due to their low concentration and small cell size
in the culture medium. The present paper aimed to study the efficiency of the
filamentous fungus Mucor circinelloides spores suspensions to harvest the green
unicellular microalga Chlorella pyrenoidosa grown in synthetic medium. Results
showed that the optimal co-culture conditions were pH=6.0, 1.25 g.L-1 glucose and
1:250 fungi to microalgae ratio with harvest efficiency of 91.08%. In addition,
the mentioned optimal conditions could be applied for actual sewage with harvest
efficiency of 92.33%. Polysaccharide concentrations measured before and after 48
h of cultivation showed that the polysaccharide of C. pyrenoidosa cultured alone
was increased by 0.047 g.L-1, while co-cultured mixture showed increase in
polysaccharides by 0.019 g.L-1. The recorded decrease in polysaccharides
concentration in the co-culture might be attributed to using of excreted
polysaccharides by M. circinelloides to grow, confirming the symbiotic
association of both organisms. Furthermore, with decreasing the pH, C.
pyrenoidosa Zeta potential was stable, while it was increased from -37.7 mV to
9.87 mV in M. circinelloides, which indicated that charge neutralization was the
mechanism of flocculation between algae and fungi.
PMID- 29964528
TI - [Effect of Zero Valent Iron on the Decline of Tetracycline Resistance Genes and
Class 1 Integrons During Thermophilic Anaerobic Digestion of Sludge].
AB - To investigate the effects of zero valent iron (Fe0) on the decline of antibiotic
resistance genes during thermophilic anaerobic digestion of sludge, the
abundances of seven tetracycline resistance genes (TC-ARGs, including tetA, tetC,
tetG, tetM, tetO, tetW, and tetX) and class 1 integron gene (intI1) were
quantified by quantitative PCR (qPCR). Also, the concentrations of volatile fatty
acids (VFAs) were determined. The correlations between the abundances of TC-ARGs
and intI1 gene and the concentrations of VFAs were discussed. The results showed
that appropriate dose of Fe0 such as 0.10 g.g-1 VSS could enhance the anaerobic
digestion process of sludge, and the production of total VFAs and acetic acid
increased significantly. The decrease in the abundances of TC-ARGs and intI1 gene
was also enhanced. However, excessive Fe0 such as 1.17 g.g-1 VSS could not
further improve the reduction in the abundances of TC-ARGs and intI1 gene,
probably resulted from the occurrence of horizontal gene transfer. The abundances
of TC-ARGs except tetO gene, as well as intI1 gene exhibited significant negative
correlation with the concentration of acetic acid, indicating that acetic acid
probably had an enhanced effect on the decline of TC-ARGs and intI1 gene during
thermophilic anaerobic digestion of sludge.
PMID- 29964529
TI - [Concentration, Sources and Ecological Risks of PAHs of Different Land Use Types
in Shenfu New City].
AB - The concentration level of polycyclic aromatic hydrocarbon (PAHs) in topsoil from
Shenfu New City in urbanization was studied. 54 topsoil samples were collected
from Shenfu New City and 4 different land uses (urban land, rural land, forest
land, cultivated land) were included. The concentration of PAHs in different land
uses was analyzed, the sources of soil PAHs were analyzed by using diagnostic
ratios and principal component analysis, and the ecological risks were calculated
using toxic equivalency concentrations of BaP and the incremental lifetime cancer
risk(ILCR)model. Results indicated that the concentrations of ?PAHs in urban
land, cultivated land, rural land and forest land were in the range of 184-18276,
230-14102, 151-3205, 303-2980 MUg.kg-1, respectively. Four land uses had similar
sources, the main sources were coal combustion and traffic emission. According to
the calculation of ecological risks, there were potential health risks for
residents in Shenfu New City, especially urban land, meanwhile, residents were
easily exposed to soil PAHs through dermal contact.
PMID- 29964530
TI - [Compositions, Sources and Health Risks of Polycyclic Aromatic Hydrocarbons
(PAHs) in Surface Dusts from Driving-schools in a City of Henan Province, China].
AB - The contamination of polycyclic aromatic hydrocarbons (PAHs) in surface dusts
attracts great attentions due to their properties of threatening human health.
Twenty-nine surface dust samples were collected from driving-schools in a city of
Henan. Concentrations of 16 priority PAHs were analyzed by gas chromatography
mass spectrometry (GC-MS). The health risks exposed to dust PAHs for three
different scenarios (working for 5 a, 10 a and 20 a in driving-school) were
estimated by the health risk assessment model (ILCRs). Source identification was
analyzed by diagnostic ratio, composition analysis, and principal component
analysis. The results showed that concentrations of the ?PAHs in dusts ranged
from 198.21 to 3400.89 MUg.kg-1, with a mean of 908.72 MUg.kg-1. Among individual
PAHs, the contents of naphthalene (Nap), phenanthrene (Phe), anthracene (Ant) and
fluoranthene (Flu) were higher, and the content of dibenzo[a, h]anthracene (DBA)
was the lowest. The dominant compounds were 2-3 ring PAHs, which accounted for
55.79%, while the 4-6 ring PAHs accounted for 44.21%. The health risks exposed to
PAHs in dust in three different scenarios were 9.27*10-8, 1.85*10-7, and 3.71*10
7 respectively; only sample J11 was with potential health risk in scenario 3, and
the other samples were all without risks. Average daily doses by dermal contact
of dust particles for the PAHs was the main exposure way. PAHs in dusts of
driving-school were mainly originated from the combustion of fossil fuels and
mixture combustion. The major sources of dust PAHs in farmland area driving
schools were natural gas and diesel combustion (56.44%), coal combustion
(26.55%), gasoline combustion and the leakage (17.01%); dust PAHs in industrial
area driving-schools were from mixture combustion (76.26%), gasoline combustion
and the leakage (22.85%), coking and coal combustion (0.89%); and dust PAHs in
mixed area driving-schools were from coal combustion (45.57%), natural gas and
diesel combustion (45.41%), gasoline combustion and the leakage (9.02%). The
concentrations and health risks of heavy metals in dusts were closely related to
the surroundings around driving-schools and the previous land use status.
PMID- 29964531
TI - [Remediation of Decabromodiphenyl Ether Contaminated Sediment Through Plant Roots
Enhanced by Exogenous Microbes].
AB - Decabromodiphenyl ether (BDE-209), a main ingredient of brominated flame
retardants, has drawn more and more attention because of the pollution it caused
in sediment. A pot experiment was conducted in a greenhouse to investigate the
impact of Brevibacillus brevis and Enterococcus casselifavus on the enhancement
of phytoremediation by Thalia dealbata, which is common in the river bank and was
found to be an effective plant for BDE-209 removal. The concentration of organic
acids, the amount of microorganisms and the ability of carbon utilization of soil
microorganisms in different experimental groups were analyzed. The results showed
that the removal rate of BDE-209 in the exogenous microbes containing groups were
higher than that of the control. And B. brevis presented the highest enhancement
of phytoremediation with the removal rate rising highest to 66% compared with the
control (non-rhizosphere group 37.93% and no plant group 39.27%) after 60 days.
The removal of BDE-209 in sediment, quantity of microorganism, concentration of
organic acids and the ability of carbon utilization of soil microorganisms in
rhizosphere sediment were higher than those in non-rhizosphere sediment.
PMID- 29964532
TI - [Impacts of Bioremediation on Microbial Communities and Different Forms of
Nitrogen in Petroleum Contaminated Soil].
AB - A laboratory study was conducted to investigate the impacts of bioremediation on
microbial communities and various nitrogen shifts in petroleum contaminated soil
by using GC-MS and Illumia MiSeq technique. Results showed the concentrations of
alkane reduced from 25987.8 mg.kg-1 to 12788.6 mg.kg-1, and the concentrations of
polycyclic aromatic hydrocarbons (PAHs) decreased from 5322.9 mg.kg-1 to 2917.2
mg.kg-1. Illumia MiSeq results showed that soil microbial communities shifted
significantly after remediation, and the relative abundance of some phylum of
hydrocarbon degraders (Firmicutes, Bacterodetes), and some genus of degraders
(Dietzia, Acinetobacter) increased. Besides, the contents of total nitrogen and
ammonia nitrogen increased firstly and then decreased during remediation.
However, the contents of nitrate nitrogen decreased at the early stage, and then
kept stable in the later stage of remediation. It can be concluded that
bioremediation effectively promoted petroleum hydrocarbon degradation, and the
different fractional hydrocarbon degradation was related to the relative
abundance of hydrocarbon degraders and available nitrogen contents.
PMID- 29964533
TI - [Effects of Rhodopseudomonas palustris PSB06 on Pepper Rhizosphere Microbial
Community Structure].
AB - The use of biological pesticide can greatly reduce the soil pollution in the
environment. Exploring the effect of biological pesticide on community diversity
and distribution of pathogenic bacteria will provide theoretic basis for
subsequent researches on biological pesticide micro-ecological control. In order
to explore the microbial ecological mechanism of pepper phytophthora blight, this
research compared the difference of microbial diversity between rhizosphere soil
of infected and healthy plants, and the effects of Rhodopseudomonas palustris
PSB06 on microbial diversities of plant rhizosphere soil were investigated using
Illumina MiSeq sequencing technology. The results showed that there was less
difference in the microbial diversity from the same soil between the seventh day
and the fourteenth day. The microbial diversity of rhizosphere soil of healthy
plants was higher than that of rhizosphere soil of infected plants. The soil
sprayed with Rhodopseudomonas palustris PSB06 exhibited the highest diversity.
Moreover, the abundance of Actinomycetes in the rhizosphere soil of healthy
plants was higher than that of infected plants, and the highest abundance of
Actinomycetes was observed in the soil sprayed with Rhodopseudomonas palustris
PSB06. The microbial diversity between rhizosphere soil of infected and healthy
plants was significantly different. Spraying Rhodopseudomonas palustris PSB06
could significantly alter the microbial community structure of the soil. It could
also increase the diversity of microorganism and the abundance of Actinomycetes
in the soil.
PMID- 29964534
TI - [Effect of Reclaimed Water on Bacterial Community Composition and Function in
Urban River Sediment].
AB - In order to study the effect of reclaimed water on bacterial community
composition and function in urban river sediment, the changes of bacteria
community diversity, composition and function in Mayu wetland upon the supply of
reclaimed water were investigated by a range of sophisticated procedures,
including Terminal Restriction Fragment Length Polymorphism(T-RFLP), 16S rRNA
clone library technology, and Real-time Quantitative PCR Detecting
System(qPCR).The results showed that carbon, nitrogen and phosphorus were major
factors driving the variation of bacterial diversity and community structure in
river sediment, and the bacteria were gradually recovered after purification in
downstream under the effect of artificial wetland. In addition, the bacterial
community in reclaimed water outfall was mainly constituted by beta
Proteobacteria, delta-Proteobacteria, Bacteroidales and Cyanobacteriain, and
epsilon-Proteobacteria, Chloroflexi and Spirochaetes were unique groups. Besides,
the major biological geochemical cycle was nitrogen, carbon and phosphorus cycle
in river sediment, which was closely related to functional genes. There were
about 45.9% of the clones related to nitrogen cycle in reclaimed water outfall,
such as Comamonas sp., higher than those of upstream and downstream (27.7% and
23.4%), 17.9% of the clones were closely related to the carbon cycle, such as
Lysobacter sp., higher than those of upstream and downstream (14.4% and 12.9%).
Furthermore, the trace of pathogenic bacteria and antibiotics in reclaimed water
also changed the transformation pattern participating in carbon and nitrogen
cycle, for example, Rhodocyclus sp. conducted nitrogen fixation by photosynthesis
in reclaimed water outfall, whereas Burkholderia sp. fixes nitrogen by ways of
plants symbiotic nitrogen fixation in upstream and downstream. This research
provides theoretical reference for studies on remediation of reclaimed water
supplying river by artificial wetland.
PMID- 29964535
TI - [Effects of Different Vegetation Types and Reclamation Years on Soil Bacterial
Community Structure in Reclaimed Mine Areas].
AB - Effects of different vegetation types (Ulmus pumila, Larix gmelinii, Armeniaca
vulgaris, Picea asperata and Robinia pseudoacacia) and reclamation years (15 and
20 years) on soil bacterial community structure in reclaimed Antaibao opencast
mine areas were investigated using polymerase chain reaction-denaturing gradient
gel electrophoresis (PCR-DGGE) and clone sequencing. For 20-year reclaimed soils,
the significantly highest and lowest bacterial diversity were found in U. pumila
and A. vulgaris stand, respectively, whereas no significant differences were
found between the other three vegetation types. Under 15-year plantations, soil
bacterial diversity index of P. asperata was significantly higher than that of R.
pseudoacacia. Soil bacterial diversity index significantly increased in R.
pseudoacacia planted soils but decreased in P. asperata treatment with the
increase of reclaimed years. No significant change of soil bacterial community
structure was observed in the same reclamation years based on the similarity
coefficient analysis, cluster analysis and principal component analysis (PCA).
Pearson correlation analysis demonstrated that bacterial diversity index was
significantly positively correlated with soil pH. Nitrospira, Sphingomonas,
Arthrobacter, Brachybacterium, Rhizobium as well as Mesorhizobium, which play
important roles in the nitrogen cycle, degradation of polycyclic aromatic
hydrocarbons and other organic matter, were identified by clone sequencing of the
DGGE bands. Our results indicated that U. pumila and P. asperata were conducive
to the recovery of soil bacterial diversity. The most dominant bacterial
community from reclaimed mine soil would be beneficial for restoring wasteland
contaminated soil and improving soil fertility.
PMID- 29964536
TI - [Characteristic of Abundances and Diversity of Carbon Dioxide Fixation Microbes
in Paddy Soils].
AB - To get a better understanding of the microbial autotrophic carbon sequestration
potential of paddy fields and its mechanisms, soil incubation experiment was
conducted for four representative paddy soils. The molecular biological
methods[quantitative PCR (qPCR), clone library and terminal-restriction fragment
length polymorphism (T-RFLP) technique] based on cbbL and cbbM genes encoding the
key enzymes[ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO)] of Calvin
cycle were used to determine the abundance and diversity of autotrophic microbes.
The results showed that, after 45 days of incubation, carbon dioxide fixation
autotrophic microbial abundances were generally increased compared with those
before incubation, and cbbL gene abundances were approximately three magnitudes
higher than those of cbbM. Dominant microbial populations varied among the four
paddy soils, and most of these OTUs were distantly related to known sequences,
only part of them could be grouped into Proteobacteria and Actinobacteria. RDA
analysis results showed that soil organic carbon (SOC), cation exchange capacity
(CEC), pH, clay, silk and sand content had significant effects on the CO2
fixation microbial community. Consequently, the results of this study provide
significant reference to understand the role of microorganisms in carbon cycle
process. The results are helpful for providing a scientific basis for scientific
management of paddy soil fertility and low carbon agriculture construction.
PMID- 29964537
TI - [Effects of Biochar Pyrolyzed at Varying Temperatures on Soil Organic Carbon and
Its Components: Influence on the Composition and Properties of Humic Substances].
AB - Application of biochar (BC) is an important way to increase soil organic carbon
sequestration. At the same time, the effect of BC on fractions and properties of
soil humic substances is concerned. A laboratory experiment was conducted to
study the influences of BC pyrolyzed at different temperatures on the composition
and properties of humic substances. The modified method for the extraction and
fractionation of humic substances was adopted in this work. The carbon (C)
contents of Humin (Hu), Humic acids (HA), Fulvic acids (FA) were analyzed by the
thermal oxidation of K2Cr2O7 and TOC analyzer, and the optical properties of HA
and FA were measured by using spectrophotometer. The results showed that the
increasing temperature (from 300 to 600C) decreased like-humic substances (LHS)
from 10.93 g.kg-1 to 0.26 g.kg-1, while the structure of theLHS tended to be
complicated. Compared with control treatment (CK), the addition of BC produced
under 400C increased the contents of HA and FA (after 240 d incubation a lower FA
content was found in treatments) and increased as BC application rate increased,
after 360 d of incubation, BC300 and BC400 significantly increased by 69.93% and
48.75% for HA (P<0.05), while decreased by 1.35% and 5.19% for FA. Higher
contents of HA and FA were found in soil samples amended with BC prepared at
above 400C only during the initial period of 3-10 d of incubation and increased
as BC application rate increased, at the end of the incubation, the contents of
HA and FA significantly decreased by 34.38%, 44.48% in BC500 treatments and
42.84%, 49.27% in the BC600 treatments (P<0.05). During the incubation, the
addition of BC significantly increased the contents of Hu (P<0.05), and the
treatments amended with BC500 were the highest. The addition of BC decreased the
relative contents of HA and FA, while increased the relative content of Hu,
indicating that the proportion of relatively stable organic carbon in the soil
was increased. The ratio of HA/FA (H/F) varied between 0.88 and 2.52 and
increased with decreasing pyrolysis temperature and increasing BC application. A
significantly lower color tonal coefficient (DeltalgK) and E4/E6 values in
treatments amended with BC produced at temperatures above 400C, indicating that
higher temperatures derived BC complicated the structure of soil humic substance,
while an opposite rend was observed in treatments amended with BC produced at
temperatures under 400C. Considering the improvement of the stability of organic
carbon, when the BC products were applied to the Loutu soil, 500C was the optimal
temperature for preparing apple-derived BC not only because it could
significantly increase the content of inert soil organic carbon, but also improve
the quality of the soil as a result of enhancing the degree of soil humification.
PMID- 29964538
TI - [Straw Composts with Composite Inoculants and Their Effects on Soil Carbon and
Nitrogen Contents and Enzyme Activity].
AB - The utilization of straw resources is of great significance to agricultural
environmental protection and sustainable agricultural development. Based on the
isolated 15 high-efficient cellulose degrading bacteria in the laboratory, the
composite inoculants (JFB-1) which can effectively degrade crop straw were
screened, and the effects of straw composts with the composite inoculants on soil
carbon and nitrogen contents and enzyme activity were studied. The results showed
that the composite inoculants could accelerate straw decomposition for 1-2 d
during single fermentation period, and the organic matter contents in straw
composts reached 403.5-515.1 g.kg-1, while the ratio of carbon and nitrogen
decreased from 10.53 to 15.30. The pot experiments found that the application
effects of rice straw composts were generally better than those of corresponding
asparagus straw composts. Compared with the control compost of rice straw, when
the application amount of rice straw compost using the composite inoculants was
150 g.kg-1, the contents of soil organic matter and total nitrogen increased by
33.5% and 7.3%, and soil urease and cellulase activities increased by 16.7% and
30.8%, respectively. Compared with no fertilization treatment, the application of
straw composts could improve soil microbial community structure, and increase
microbial diversity indices. When the application amount of rice straw compost
using the composite inoculants was 100 g.kg-1, the biomass of common Chinese
cabbage cultivated for 30 d increased by 46.4% compared to the control compost of
rice straw. These results indicated that the composite inoculants have great
application potential in straw composts.
PMID- 29964539
TI - [Comparative Analysis on Effect of Wheat Straw and Its Biochar Amendment on Net
Global Warming Potential Under Wheat-Maize Rotation Ecosystem in the Guanzhong
Plain].
AB - In order to compare the differences in carbon sequestration and greenhouse gas
mitigation between straw and straw-derived biochar amendment, a field experiment
was conducted with simultaneous measurement of carbon dioxide (CO2), methane
(CH4) and nitrous oxide (N2O) emissions, crop yield, soil organic carbon (SOC)
content and net global warming potential (NGWP) in a wheat-maize rotation
cropping system from the loess plateau of China. Five treatments were
included:control (no straw incorporation, no straw-derived biochar amendment and
no fertilization, CK), fertilization (no straw incorporation and no straw-derived
biochar amendment, F), straw with fertilization (wheat straw incorporated at 8
t.hm-2, FS), low straw-derived biochar (8 t.hm-2) with fertilization (FBlow) and
high straw-derived biochar (16 t.hm-2) with fertilization (FBhigh). Wheat yield
increased by 30.9%, 66.3% and 36.6% under FS, FBlow and FBhigh treatment, as
compared to the F treatment, respectively. However, maize yield decreased by
14.1%, 18.0% and 24.6% under FS, CK and FBhigh treatment as compared to the F
treatment, respectively. There was no significant difference between FBlow and F
treatment. Annual CO2 emission increased by 60.2% under FS treatment, but
decreased by 14.4% under FBhigh treatment as compared to the F treatment,
respectively. Annual N2O emission decreased by 27.6% and 38.7% under FBlow and
FBhigh treatment as compared to the F treatment, respectively. However, no
significant difference was observed under straw application. Overall, the NGWP
decreased by 24.13 and 58.44 t.hm-2 under FBlow and FBhigh treatment as compared
to the F treatment, respectively. And the NGHGI decreased by 1.78 and 5.06 t.t-1
under FBlow and FBhigh treatment as compared to the F treatment, respectively. In
summary, we conclude that the fertilization with 16 t.hm-2 biochar amendment can
be used as an effective management to improve the crop yield and reduce the net
global warming potential under the wheat-maize rotation system.
PMID- 29964540
TI - [Isolation and Identification of a Chlorobenzene-degrading Bacterium and Its
Degradation Characteristics].
AB - A bacterium strain LW26 which could utilize chlorobenzene (CB) as sole carbon and
energy source was isolated from a biotrickling filter reactor treating CB
contaminated off-gas. Based on its morphological and physiological
characteristics, as well as the analysis of 16S rRNA gene sequence and Biolog
test, the strain LW26 was identified as Delftia tsuruhatensis. To our best
knowledge, it is the first time that the strain Delftia tsuruhatensis was applied
for CB purification. In this study, the effects of temperature, pH, initial CB
concentration and Cl- concentration on the biodegradation were investigated. The
results showed that the optimal temperature and pH for CB biodegradation were 25C
and 7.0,respectively; the maximum CB tolerated concentration for LW26 was as high
as 500 mg.L-1; when the concentration of Cl- was above 0.14 mol.L-1, the CB
degradation was significantly restrained. The degrading process of the strain
LW26 followed the Haldane kinetic model and the maximum specific growth rate and
the maximum specific degradation rate were 0.42 h-1 and 2.53 h-1, respectively.GC
MS analysis of the metabolites revealed that CB was firstly converted to o
chlorophenol by strain LW26. Combined with the activity of catechol dioxygenase,
it can be speculated that CB was finally mineralized to CO2, or converted to cell
biomass after processes of ortho cleavage,dechlorination and oxidation.
PMID- 29964541
TI - [Isolation, Identification and Metabolic Characteristics of a Heterotrophic
Denitrifying Sulfur Bacterial Strain].
AB - Organics,sulfide and nitrogen compounds in industrial wastewater are significant
challenges for wastewater treatment. These pollutants could be removed
simultaneously from wastewater treatment system using biological technologies. In
this study, a heterotrophic denitrifying sulfur bacterial strain HDD1 was
isolated from wastewater treatment bioreactor. Strain HDD1 was identified as
Thauera sp. based on the 16S rRNA gene phylogenetic analysis and physiological
characteristics. Acetate and sulfide could be utilized as electron donors and
nitrate as electron acceptor for respiration in Thauera sp. HDD1. The acetate
(300 mg.L-1), sulfide (200 mg.L-1) and nitrate (487 mg.L-1) were completely
metabolized and removed within 15 hours. The main product of sulfide oxidation
was elemental sulfur as identified by scanning electron microscope and energy
dispersive spectrometer. These results suggest that the newly isolated Thauera
sp. HDD1 could be used for simultaneous industrial wastewater treatment and
elemental sulfur resource recovery.
PMID- 29964543
TI - [Effects of Nitrogen Application on Selenium Uptake, Translocation and
Distribution in Winter Wheat].
AB - In order to better understand the effects of nitrogen application on
accumulation, translocation and distribution of selenium in winter wheat and to
provide theoretical reference for reasonable nitrogen application and increasing
selenium content of grains. A pot experiment was carried out under greenhouse
conditions with Se1 (0.74 mg.kg-1) or Se2 (2.60 mg.kg-1) levels of selenium, and
each Se treatment was supplied with N1 (100 mg.kg-1) or N2 (200 mg.kg-1) levels
of nitrogen, respectively. Selenium concentrations and biomass amounts of
different parts of wheat were determined at jointing and maturity stage. The
results showed that grain yield increased with increasing nitrogen levels by
13.2% and 24.0% in Se1 and Se2 treatment, respectively. Regardless of N rate, Se
concentration of wheat increased with raising Se amended rate (P<0.01).
Increasing nitrogen application could promote Se uptake of root and thus increase
the selenium concentration of wheat grains and leaves, which was greater in Se1
treatment than in Se2 treatments. Se concentrations in wheat grain increased by
22.6% and 12.1% with the increasing N application rate in low and high Se
treatment, respectively. The distribution ratios of Se in each organ ranked the
same as BCFs, following the order of leaf > grain > glume > root. Increasing N
fertilization increased the distribution ratio of Se in grains by 11.1% and 25.9%
in low and high selenate treatments, respectively. High nitrogen fertilization
could promote uptake and translocation of Se in wheat under low Se conditions,
and improve Se use efficiency as well in the agricultural production.
PMID- 29964542
TI - [Effects of Continuous Application of Sewage Sludge Compost on Heavy Metals
Accumulation and Mobility Characteristics in Soil Profile and on Heavy Metals
Uptake of Wheat].
AB - The use of sewage sludge compost(SSC)as fertilizer may cause increased leaching
due to its high content of heavy metals and thus pose a threat to groundwater
quality. The effect of SSC application on heavy metals leaching in calcareous
soils has been studied in field trials, which provides basis for determining
heavy metals environmental capacity and preventing metal pollution in farmland
soil scientifically. The results indicated that the contents of Cu, Zn elevated
obviously with the increase of the age and the dosage of SSC utilization in the
topsoil(0-15 cm) under 4-year continuous application of SSC. Under higher levels
of the compost treatment, the heavy metals Cu and Zn were found to migrate into
the 15-30 cm soil and 60-90 cm soil under the experimental condition.
Nevertheless, the majority of Cu and Zn from SSC accumulated in topsoil and the
highest accumulation rates could reach 75.3% for Cu and 85.9% for Zn. The
contents of Cd, Pb increased significantly in topsoil after 4-year continuous
application of SSC, and their increases could reach 57.2%-165.2% for Cd and 13%
34% for Pb compared with CK. At 60-90 cm soil, the contents of Cr, As and Pb were
also significantly higher than those in CK treatment. Application of SSC not only
caused accumulation of some heavy metals in topsoil but also leached heavy metals
located in the subsurface soil down in this experiment. Continuous utilization of
SSC increased Zn concentration of wheat grain, and the increase could reach 13.3%
47.9%. For the concentrations of Cr and Pb in wheat grain, the values exceeded
the national food and healthy standards value (GB 2762-2012) in part of compost
treatments. The cumulative ratio of heavy metals carried out by wheat were all
below 10% after 4-year experiment, wheat grain carried much more Cu, Zn out than
wheat straw, but it was opposite for Cr, As, Cd, Pb. The cumulative ratio of
heavy metals carried by wheat decreased with the increasing level of SSC
utilization. The amounts of heavy metals migrated to deeper soil should be
considered when determining the environmental capacity of heavy metals in
farmland soil.
PMID- 29964544
TI - [Accumulation and Biotransformation in Typical Freshwater Algae Species
Influenced by Titanium Dioxide Nanoparticles Under Long-term Exposure].
AB - In the present study, the accumulation and biotransformation of arsenate in
typical freshwater algae species were examined under long-term influence of
titanium dioxide nanoparticles (nano-TiO2). Results showed that different algae
species had largely varied capacities of accumulation and biotransformation of
arsenate. The arsenic accumulation reached (819.66+/-11.25) MUg.g-1 DW in
Scenedesmus obliquus, which was higher than that in Microcystis aeruginosa of
(355.95+/-8.31) MUg.g-1 DW. Nano-TiO2 increased arsenic accumulation in these
exposed algae species, and then reduced arsenic levels in the relative culture
media. Furthermore, nano-TiO2 improved arsenic biotransformation in the exposed
algae, and the organic arsenic was dimethylarsinous acid (DMA) and
monomethylarsonous acid (MMA) in Microcystis aeruginosa and Scenedesmus obliquus,
respectively. Additionally, the release of organic arsenic was lower from the
exposed algae in nano-TiO2 treatments than in the control, indicating that nano
TiO2 couldn't stimulate the release of organic arsenic from algae under long-term
exposure. These results could improve insights on the ecological risk of nano
TiO2 associated with arsenic in the environment.
PMID- 29964546
TI - [Regional Transport Matrix Study of PM2.5 in Jingjinji Region, 2015].
AB - By coupling particle source apportionment technology (PSAT) with a comprehensive
air quality model with extensions (CAMx), the regional transport matrix of PM2.5
was built for 13 cities in the Jingjinji Region in 2015. Results showed that the
major contributor to PM2.5 was local source emissions, contributing 21.49%
68.74%, The internal transport from in-region sources contributed 13.31%-54.62%
and the external transport from out-region sources contributing 13.32%-45.02%
were also significant. The spatio-temporal distribution of the PM2.5 transport
matrix was characterized by geographical, meteorological, and source patterns.
Local emissions exerted the most significant impact on the central part of
Jingjinji in winter, while regional transport contributed more to the southern
region in other seasons. By assessing the input/output and activity of PM2.5
transport, Langfang, Hengshui, Chengde, Qinhuangdao, and Xingtai were receptors;
Tianjin, Cangzhou, Tangshan, Beijing, Shijiazhuang, and Handan were sources, and
Zhangjiakou and Baoding had a balanced transportation mode. The seasonal matrix
of PM2.5 showed significant transport between Beijing and Langfang, Baoding,
Chengde, Tianjin, Cangzhou, while the city list for Tianjin and Shijiazhuang
differed slightly.
PMID- 29964547
TI - [Effect of Atmospheric Haze Based on Multi-source Remote Sensing Data Considering
the Size Effect of Landscape Sources and Sinks].
AB - Based on a geo-weighted regression model, this study analyzes the relationship
between the landscape patterns of sources and sinks in urban areas and
atmospheric haze pollution. First, the classification result of the study area is
divided into a number of square grids with side lengths of 2-9 km. Heterogeneity
indices at different scales are calculated and compared to select an optimal
scale for the following analysis. Then, the category level landscape indices,
such as PLAND, PD, COHEDION, LPI, and FRAC_MN, are calculated in each grid. The
aerosol optical thickness (AOD) of Wuhan is used to represent the degree of
atmospheric haze pollution. Furthermore, the mean value of the pixels in each
grid is regarded as the value of the grid's center. Next, the landscape sources
and sinks of atmospheric haze pollution are selected based on the analysis of the
correlation between landscape indices and AOD. To make the following analysis
more efficient, the indices selected previously are determined using their
correlation coefficients. Finally, the geo-weighted regression analysis model is
used to analyze the relationship between the landscape indices of the category
level and AOD. In addition, the influences of industrial, commercial, and
residential areas on haze pollution are analyzed based on the result of the
classification of urban functional areas. The results show that the heterogeneity
of the whole landscape is most obvious at a 6 km scale, so 6 km is the optimal
scale for the analysis. The landscape sources of atmospheric haze pollution are
the buildings, and the landscape sinks are shrubs and woodland. Reducing the
proportion of landscape source area and increasing the degree of fragmentation
can cut down aerosol optical thickness. Distributing the landscape sources and
sinks evenly and interspersedly could effectively reduce aerosol optical
thickness, which represents atmospheric haze pollution. For Wuhan City, the main
sources of haze pollution are commercial and residential areas in the city
center, representing public sources. Since it is not easy to adjust existing
facilities and infrastructure, adjusting built-up areas slightly and planning
reasonably for those areas that are not yet built up can reduce atmospheric haze
pollution.
PMID- 29964545
TI - [Sorption of p-Nitrophenol by Biochars of Corncob Prepared at Different Pyrolysis
Temperatures].
AB - Sorption of p-nitrophenol (PNP) on biochars prepared from pyrolysis of corncob in
the temperature range of 200-600C (CC200-CC600) was investigated. Sorption
mechanisms were discussed. Pyrolysis temperature showed a pronounced effect on
properties of biochars. Decreases in molar H/C, O/C and (O+N)/C ratios were
resulted from removal of H- and O-containing functional groups with increasing
pyrolysis temperature, and produced biochars with low polarity and high
aromaticity. The isotherms data were well described by the Freundlich model.
Batch sorption experiments showed that the PNP sorption was strongly dependent on
the properties of biochars. A linear relationship was observed between sorption
parameters (n and KF) and properties of biochars such as molar elemental
ratios[H/C, O/C, and (O+N)/C]. The sorption and partition fractions were
quantified by isotherm separation method. PNP sorption on biochar produced at
200C was linear due to partition on uncarbonized organic matter in biochar, while
PNP sorption on biochars produced at 300-600C was nonlinear and adsorption
dominant for all the biochars via pi-pi electron donor-acceptor interaction and
pore-filling.
PMID- 29964548
TI - [Space-Time Estimations and Mapping of PM2.5 Fine Particulates Based on Multi
source Data].
AB - PM2.5 pollution in China has become an extreme environmental and social problem
and has generated widespread public concern. We estimate ground-level PM2.5 from
satellite-derived aerosol optical depth (AOD), topography data, meteorological
data, and pollutant emissions using a new technique, Bayesian maximum entropy
(BME) combined with geographically weighted regression (GWR), to evaluate the
spatial and temporal characteristics of PM2.5 exposure in an eastern region of
China in winter. The overall 10-fold cross-validation R2 is 0.92, and the root
mean squared prediction error (RMSE) is 8.32 MUg.m-3. The mean prediction error
(MPE) of the predicted monthly PM2.5 is -0.042 MUg.m-3, the mean absolute
prediction error (MAE) is 4.60 MUg.m-3. Compared with the results of the
Geographically Weighted Regression model-GWR (R2=0.71, RMSE=15.68 MUg.m-3, MPE=
0.095 MUg.m-3, MAE=11.14 MUg.m-3), the prediction by the BME were greatly
improved. In this location, the high PM2.5concentration area is mainly
concentrated in North China, the Yangtze River Delta, and Sichuan Basin. The low
concentration area is mainly concentrated in the south of China, including the
Pearl River Delta and southwest of Yunnan. Temporally, there is migration trend
from the coastal areas inland, and PM2.5 pollution is most serious in December
2015 and January 2016. It is relatively low in November 2015 and February 2016.
PMID- 29964550
TI - [Aerosol Chemical Characteristics for Different Air Pollution Levels in North
Suburban Nanjing].
AB - PM2.5samples were collected in a northern suburb of Nanjing during the winter of
2015. Water soluble ions and carbonaceous substances under different air quality
levels were analyzed by an 850 professional IC-type ion chromatograph produced by
Metrohm and a Model 2001A carbon analyzer. The results show that the average mass
concentration of PM2.5, SO42-, NO3-, and NH4+ during heavy pollution days was
4.0, 6.4, 3.1, and 3.9 times higher than on clear days, respectively. Three main
secondary ions were all in the form of (NH4)2SO4 and NH4NO3 on all days. Two
kinds of acid pollution days were mainly affected by the flow source. The
proportion of fixed sources on the heavy pollution days was greater than on the
light/moderate pollution days. The highest mass concentrations of organic carbon
(OC) and elemental carbon (EC) were 49.8 MUg.m-3 and 10.3 MUg.m-3, respectively.
The average concentration of SOC on clear days was the lowest (4.28 MUg.m-3). The
proportion of secondary organic carbon (SOC) in the OC on clear days was more
than on the other two pollution days (41.14%). Coal combustion and motor vehicle
exhaust emissions were the main contributors to carbonaceous substances by
abundances of carbonaceous components.
PMID- 29964549
TI - [Exposure Level of Population and Economy in Zhejiang Province Considering the
Background of PM2.5 in East China].
AB - Using the satellite-derived Fine Particulate Matter (PM2.5) data of global high
precision products during 1998-2012, detailed characteristics of PM2.5
distribution over East China and its change are given, and the PM2.5 exposure
levels for population and economy in Zhejiang is further analyzed in this
context. The results show that the overall variability of the regional average
value of PM2.5 concentration exhibits an increasing trend followed by a decrease
during 1998-2012, which is consistent in both the East China and Zhejiang
provinces; the turning point occurs around 2007-2009. In the initial years (1998
2000), annual average PM2.5 concentrations are below 50 MUg.m-3 in the southern
part of East China and eastern part of Shandong, while it is 50-75 MUg.m-3 in
other areas. During this period, 51.8% of the area in East China and 21.1% of the
area in Zhejiang have PM2.5 concentrations larger than 35 MUg.m-3 (Air quality
standard value in China). The rising trend in PM2.5 concentration is extremely
obvious in 1998-2009; the mean linear trend over East China is 2.58 MUg.(m3.a)-1,
while it is 1.43 MUg.(m3.a)-1 over Zhejiang province. PM2.5 concentration reaches
its maximum during 2007-2009. The area where PM2.5 concentration is larger than
35 MUg.m-3 reaches 82.1% in East China and 65.9% in Zhejiang province. After
that, the PM2.5 concentration begins to decrease in each region, and the average
change trend in East China and Zhejiang are -1.75 MUg.(m3.a)-1 and -1.58
MUg.(m3.a)-1, respectively. The regional area in which PM2.5concentrations
aregreater than 35 MUg.m-3 displays a slight decline during 2010-2012, which
suggests that the energy conservation and emission reduction plan proposed by the
Chinese government and associated measures may play a vital role in improving air
quality of East China. In 2010, the proportion of the population and GDP for
which the PM2.5 exposure level exceeded 35 MUg.m-3 were 74.0% and 70.8%,
respectively, of which 38.1% of the population lives in an environment where
annual average PM2.5 concentrations are more than 50 MUg.m-3. In addition, 38.9%
of the GDP is produced in an environment with annual average PM2.5 concentrations
more than 50 MUg.m-3.
PMID- 29964551
TI - [Seasonal Variation of Carbon Fractions in PM2.5 in Heze].
AB - PM2.5 samples were collected in Heze from August 2015 to April 2016. Eight carbon
fractions were analyzed by a thermal/optical carbon analyzer, and organic carbon
(OC) and elemental carbon (EC) analyses were obtained. The OC/EC ratio and the
correlation between OC and EC were analyzed. Secondary organic carbon (SOC) mass
concentration was estimated by the OC/EC ratio method; and eight carbon fractions
were analyzed using a principal component analysis. The results showed that:1 The
annual average mass concentrations of OC and EC were 1.2-60.6 MUg.m-3 and 0.6
24.8 MUg.m-3, respectively; and the characterization of OC and EC percentages in
PM2.5 during different seasons were similar with winter > spring > autumn >
summer. 2 The annual average OC/EC ratio was 2.6+/-1.0, and the correlations
between OC and EC during spring, summer, autumn, and winter were 0.91, 0.56,
0.86, and 0.75, respectively, and the estimated mass concentration of SOC was
(4.7+/-5.0) MUg.m-3. 3 The characterization of eight carbon fractions percentages
in PM2.5 in the different seasons demonstrated similar seasonal variations, with
EC1 having the highest percentage and EC3 having the lowest percentage. The
result of the principal component analysis showed that coal burning, motor
vehicle emissions, and biomass burning were the major sources of carbon.
PMID- 29964552
TI - [Characteristics and Source Apportionment of Water-soluble Inorganic Ions in Road
Dust PM2.5 in Selected Cities in Liaoning Province].
AB - In order to collect comprehensive information on the characteristics and sources
of water-soluble inorganic ions in road dust (RD) PM2.5 in Liaoning Province,
samples of road dust were collected in 2014 and 2016 in Anshan and Panjin and
then re-suspended on filters using an NK-ZXF sampler. The concentrations of the
major water-soluble inorganic ions were analyzed by ion chromatography. A
correlation analysis, ratios, and a principal component analysis were used to
analyze the sources of RD. The results showed that the total water-soluble
inorganic ions in Panjin and Anshan accounted for 5.83%+/-3.34% and 5.84%+/-1.15%
in RD PM2.5, respectively. NH4+, SO42-, and NO3- in RD PM2.5 coexisted in the
forms of (NH4)2SO4, and NH4NO3 in Panjin, and NH4HSO4 and NH4NO3 in Anshan. The
average values of NO3-/SO42- were 0.52+/-0.55 and 0.46+/-0.13 for Panjin and
Anshan, respectively, indicating that the effects of stationary sources (e.g.,
coal combustion) on PM2.5 were more significant. The main sources of RD PM2.5 in
Panjin were biomass burning, sea salt particles, construction dust, and mobile
sources, while the main sources of RD PM2.5 in Anshan were coal combustion,
biomass burning, sea salt particles, and steel smelting dust.
PMID- 29964553
TI - [Characteristics of the Size Distribution of Water-soluble Ions During a Heavy
Pollution Episode in the Winter in Tianjin].
AB - To characterize the size distribution of water-soluble inorganic ions (WSII)
during a heavy pollution episode, particle samples were collected by an Andersen
cascade sampler in Tianjin in January 2014, and the concentrations of eight WSII
(Na+, NH4+, K+, Mg2+, Ca2+, Cl-, NO3-, and SO42-) during a typical haze episode
were analyzed by ion chromatography. The sources and formation mechanisms of WSII
were analyzed based on their size distributions. The results showed that the
daily average concentrations of PM2.5 and PM10 were (138+/-100) MUg.m-3 and
(227+/-142) MUg.m-3, respectively, and the average concentration of total WSII
concentrations (TWSII) in the coarse and fine particles were (34.07+6.16) MUg.m-3
and (104.16+51.76) MUg.m-3, respectively. The concentrations of SO42-, NO3-, and
NH4+ in the fine particles were much higher than concentrations of the other
ions, and there were strong correlations between these three ions. The TWSII on
clear days, light pollution days, and heavy pollution days were (41.55+/-12.41)
MUg.m-3, (94.46+/-31.19) MUg.m-3, and (147.55+/-27.76) MUg.m-3, respectively. On
clear days, SO42- showed a unimodal distribution, peaking at 0.43-0.65 MUm; and
NO3- showed a trimodal distribution, peaking at 0.43-0.65 MUm, 2.1-3.3 MUm, and
5.8-9.0 MUm. NH4+ had a bimodal distribution, peaking at 0.43-0.65 MUm and 4.7
5.8 MUm. On heavy pollution days, however, the size distributions of these three
secondary inorganic ions switched to a unimodal size distribution, peaking at
0.65-1.1 MUm. Unimodal NH4+ mainly coexisted with SO42- and NO3-, and the excess
NH4+ was found to be combined with Cl- in the fine particles. In the coarse
particles, NH4+ completely coexisted with SO42- and NO3-.
PMID- 29964554
TI - [Physico-chemical Characteristic Analysis of PM2.5 in the Highway Tunnel in the
Plateau City of Kunming].
AB - This research aimed to determine the characteristics of the motor vehicle exhaust
emissions in the plateau area. The PM2.5 was evaluated in the Caohai Tunnel of
Kunming for this study by measuring the water-soluble inorganic ions,
carbonaceous species, polycyclic aromatic hydrocarbons (PAHs), and inorganic
elements in air samples. The results showed that the mass concentration of PM2.5
in the tunnel was about 225.65-312.84 MUg.m-3, which is 11-14 times the PM2.5
concentration in the ambient atmosphere. The carbonaceous species were the most
abundant species, constituting 35.73% of the total PM2 5 mass, followed by
inorganic elements constituting about 21.78% and the water-soluble inorganic ions
in the range of 4.79%-5.52%. The smallest proportion of the PM2.5 was PAH,
constituting about 0.25%-0.32%. The Ca2+ and SO42- concentrations were the
highest among the water-soluble inorganic ions, which accounted for about 77.78%
80.17% of the total ions and from the crust source. NH4+ and NO3- are relatively
high, coming mainly from automobile exhausts. The 4 and 6 ring PAHs with higher
molecular weight and lower volatility were the dominant components of PM2.5 in
the Caohai Tunnel. The automobile exhaust contributing to PAHs in PM2.5 is very
significant. The most poisonous single BaP concentration is 23-29 times higher
than the state regulations exposure limit, and it has reached a hazardous level.
It is obvious that there are health risks from the exposure to PM2.5 in the
plateau highway tunnel. A principal component analysis (PCA) showed that the
sources of road dust and automobile exhaust emission were about 61.64%, followed
by mechanical wear and emissions that accounted for about 17.49% and tire wear
emission sources that accounted for 9.11% of the total PM2.5. Under the
conditions of hypobaric hypoxia in the Yun-Gui plateau, there is a greater chance
of incomplete combustion of motor vehicle fuels, resulting in the increase in OC
and PAHs in PM2.5 emissions.
PMID- 29964555
TI - [Characteristics Analysis of the Surface Ozone Concentration of China in 2015].
AB - Surface ozone concentration data from 189 cities in China in 2015 were processed
by ArcGIS software in order to obtain the characteristics of the surface ozone
concentration, such as time and space, topographical features, temperature, etc.
The trend for surface ozone concentration was a decrease followed by an increase
in China in 2015. The concentrations during the four seasons followed the
order:summer > autumn > spring > winter, and the maximum appeared in July. The
ozone pollution of East China, South China, and North China were more serious
than other regions in China. The variation of longitude had a small influence on
the ozone concentration, while the influence of latitude is significant.
According to the analysis contrasting three different topographies in the same
latitude, the influence of topography on ozone concentration was negligible.
Furthermore, the research found a significant positive correlation between
surface ozone concentration and temperature.
PMID- 29964556
TI - [Effects of Different Precious Metal Loads of CDPF on Characteristics of VOCs
Emissions from a Diesel Bus].
AB - Based on heavy chassis dynamometers, an experimental study was conducted in a
diesel bus with proton transfer reaction mass spectrometry (PTR-MS). It
investigated the effects of volatile organic compound (VOC) emission
characteristics with three different diesel oxidation catalyst (DOC)+catalyzed
diesel particulate filter (CDPF) after-treatments for a typical Chinese city bus
driving cycle (CCBC). The results reveal that the major compounds from the diesel
bus are OVOCs, aromatic hydrocarbons, alkenes, alkanes, nitrogenous organic
compounds, and polycyclic aromatic hydrocarbons (PAH), and that the OVOCs account
for more than 50%of the total VOCs. With the same precious metal composition and
ratio of the proportion in the CDPF catalyst, the emissions of VOCs decrease with
an increase in precious metal load. The emission reduction rates of the VOCs are
36.2%, 40.1%, and 41.4%, respectively, when the precious metal loads are 15 g.ft
3 (type A after-treatment device), 25 g.ft-3 (type B), and 35 g.ft-3 (type C).
The average emission rates of alkanes for the three kinds of DOC+CDPF after
treatments are all over 59% for the entire CCBC cycle. The type C after-treatment
device can reduce the alkane emissions by 70.2%, with a slight advantage for the
OVOC reduction compared with type A and type B devices. For unsaturated
hydrocarbons, including aromatic hydrocarbons, alkenes, and PAHs, the after
treatment devices have a catalytic effect, but there is no significant difference
between them. The emissions of nitrogenous organic compounds are greatly
decreased, by 50.5%, with the type A after-treatment, but the reduction rate
decreases with an increase in precious metal load. In addition, OVOCs, aromatic
hydrocarbons, and alkenes are the most important contributors to ozone formation.
The adoption of DOC+CDPF reduces the emissions of VOCs and, therefore, the ozone
formation potential. Taking into account the emission reduction rates and costs
of the three different after-treatments and for weighting coefficients of 0.8 and
0.2, respectively, the type B after-treatment is the optimal solution.
PMID- 29964557
TI - [Influence of ENSO Events on the Hydrogen (delta2H) and Oxygen (delta18O)
Isotopic Values of Precipitation in Shanghai].
AB - An analysis of the effect of ENSO events with different strengths on the isotopic
composition of precipitation is conducted based on test data for 206
precipitation samples collected from January 2012 to February 2017 in Shanghai
coupled with the archives for Nanjing, Wuhan, Fuzhou, and Hong Kong from 1961 to
2012 from the Global Network of Isotopes in Precipitation (GNIP) database. During
the research periods, the deltaD and delta18O values in precipitation are lower
in summer and autumn but higher in winter and spring. The slope and intercept of
the atmospheric precipitation lines during El Nino events are larger than during
other times, while anti-temperature, precipitation amount, and vapor pressure
effects are more significant than during La Nina events. The delta18O and
deuterium excess values (value of d) of rainfall in Shanghai during El Nino and
La Nina events of varied strengths have an obvious negative correlation with the
oceanic Nino index (ONI), sea surface temperature anomaly (SSTA), and the extreme
and cumulative values of ONI. Moreover, ENSO events are closely intertwined with
the correlation between delta18O isotopic value in precipitation, ONI, and SSTA.
PMID- 29964558
TI - [Deposition of Sulfur, Nitrogen and Mercury in Two Typical Forest Ecosystems in
Southern China].
AB - Bulk precipitation collectors and canopy throughfall collectors were applied to
measure the deposition of sulfur, nitrogen, and mercury at two forest ecology
stations, Qianyanzhou (QYZ) in Jiangxi Province and Huitong (HT) in Hunan
Province, from December 2013 to November 2014. During the observation period, the
volume weighted average concentrations of SO42--S, NO3--N, NH4+-N, and Hg at QYZ
station were 1.89 mg.L-1, 0.957 mg.L-1, 0.401 mg.L-1, and 12.5 ng.L-1 in the bulk
precipitation, respectively, and 2.39 mg.L-1, 1.18 mg.L-1, 0.897 mg.L-1, and 22.2
ng.L-1 in the throughfall, respectively. The concentrations of these components
increased by different proportions for the bulk precipitation compared to the
throughfall. At HT station, the average concentrations of SO42--S, NO3--N, NH4+
N, and Hg in the throughfall were 2.93 mg.L-1, 1.60 mg.L-1, 0.502 mg.L-1, and
22.0 ng.L-1, respectively. In addition, atmospheric deposition fluxes based on
the throughfall were 3.56 g.(m2.a)-1 for sulfur, 3.02 g.(m2.a)-1 for nitrogen,
and 30.6 MUg.(m2.a)-1 for mercury at QYZ station, while the corresponding fluxes
were 6.18 g.(m2.a)-1, 4.48 g.(m2.a)-1, and 37.3 MUg.(m2.a)-1 at HT station. The
deposition rates of all three elements were the highest in summer. The
contribution of dry deposition to the total deposition of mercury was similar to
that of wet deposition, while wet deposition contributed more to the total
deposition of sulfur and nitrogen than did dry deposition. Unlike sulfur and
nitrogen depositions, which were mainly derived from anthropogenic sources,
mercury deposition might have a greater contribution from natural sources,
especially at HT station.
PMID- 29964559
TI - [Spatial and Temporal Variability of CO2 Emissions from the Xin'anjiang
Reservoir].
AB - Xin'anjiang Reservoir is the largest reservoir in eastern China, with a surface
area of 580 km2 and a mean depth of 30 m. It is in an oligotrophic or mesotrophic
state at present. This study measured carbon dioxide (CO2) emissions from the
upstream river, the reservoir's main body, and the river downstream of the
Xin'anjiang Reservoir to investigate the spatial and seasonal variability of CO2
emissions from the water surface using static floating chambers and gas
chromatography. Results showed that the downstream river had, significantly, the
highest CO2 emission flux[(1535.00+/-1447.46) mg.(m2.h)-1], followed by the
upstream river[(120.39+/-135.41) mg.(m2.h)-1]. The reservoir's main body had the
lowest flux[(36.65-61.94) mg.(m2.h)-1]. The high CO2 emission flux in the
downstream river was probably influenced by turbulence during the discharge
periods, which would allow the dissolved CO2 in the hypolimnion before the dam to
be released to the atmosphere in the watercourse of the downstream river.
However, the CO2 emission flux decreased with distance to the dam, likely because
of the drop in strength of the turbulence. Moreover, there was an obvious
alternation between CO2 source and CO2 sink in the main body of the reservoir,
with CO2 sources in autumn and winter and CO2 sinks in spring and summer. The
maximum and minimum CO2 emission values occurred in winter and spring,
respectively. Such variability in the CO2 emissions was probably influenced by
the bloom of alga in spring and summer, because dissolved CO2 in the water was
absorbed by the respiration of alga. However, hydrologic conditions were unstable
in the upstream river due to a fast water flow, so alga was difficult to bloom
there, and a CO2 source was observed throughout the year, except during April and
August. The measurement of the flux from the upstream river, main body, and
downstream river required a long period for the investigation of greenhouse gas
emissions to avoid underestimating the total CO2 emission from a hydroelectric
reservoir system.
PMID- 29964560
TI - [Evaluation of Temporal and Spatial Variation Characteristics of Nutrients in
Surface Sediment in the Three Gorges Reservoir Area].
AB - With the construction of the Three Gorges Dam, the river flow pattern and
sediment dynamics are expected to be affected. As a consequence, the sediment
traits could be impacted by these changes. The temporal and spatial variation
characteristics of the nutrient content from 2000 to 2015 in surface sediment
were analyzed in the main stream from Jiangjin to the dam site section of the
Yangtze River and in the estuaries of the representative input tributaries of the
Three Gorges Reservoir, such as the Jialing River, Yulin River, Wujiang River,
Xiaojiang River, Daning River, and Xiangxi River. Then, the state of the
pollution was assessed. Results revealed that the average concentrations of total
phosphorus (TP) in the surface sediments of the main stream ranged from 678.2 to
928.6 mg.kg-1, the average contents of total nitrogen (TN) ranged from 0.203% to
0.362%, the average contents of potassium ranged from 1.74% to 2.37%, and the
average contents of organic matter ranged from 0.94% to 1.54%. The average
concentrations of TP in the estuaries of the representative input tributaries
ranged from 490.1 to 832.3 mg.kg-1, the average contents of TN ranged from 0.257%
to 0.495%, the average contents of potassium ranged from 1.69% to 2.32%, and the
average contents of organic matter ranged from 1.21% to 2.27%. The concentrations
of TP and potassium in the study sections were generally within background
concentration ranges, while the concentrations of TN were obviously above
background levels, and the concentrations of organic matter were obviously below
background levels. The nutrient contents in the surface sediment did not display
significant differences among the study sites; however, the distributions of
different nutrient contents along the river varied widely. Although the nutrient
contents in the surface sediments fluctuated somewhat during different flow
periods, they were seemingly unaffected by the impoundment, since no obvious
enrichment was observed throughout the impoundment. The evaluation of organic
index indicated a clean state for the surface sediments in the majority of the
study area, while there was a moderately polluted state in some local sections.
The evaluation of nitrogen pollution indicated a polluted state for most
sections. Overall, the nutrients in the surface sediments of the Three Gorges
Reservoir showed moderate ecological risks, possibly caused by TP and TN.
PMID- 29964561
TI - [Distribution of Different Mercury Species in the Waterbody at Sanmenxia
Reservoir].
AB - In order to obtain the distribution of different species of mercury (Hg) in the
water in the Sanmenxia Reservoir, cold vapor atomic fluorescence spectrometry
(CVAFS) and aqueous phase ethylation derivatization-gas chromatography-atomic
fluorescence spectrometry (GC-CVAFS) methods were used for the analysis of total
Hg (THg) and methylmercury (MeHg) in water and sediment samples, respectively. It
was found that the levels of THg, dissolved mercury, and particulate mercury in
the water ranged from 1.65-9.65, 0.80-3.16, and 0.70-7.81 ng.L-1, respectively.
The THg in the water could meet the requirement for the Class I criterion in the
national surface water environmental quality standard (GB 3838-2002). The amounts
of MeHg, dissolved MeHg, and particulate MeHg in the water samples were 0.05
0.36, 0.02-0.14, and ND-0.26 ng.L-1, respectively. No evident seasonal or spatial
patterns for Hg were observed. The THg and MeHg in the Sanmenxia Reservoir were
within the ranges for those in uncontaminated waterbodies worldwide. The amount
of THg in the sediments was (92.96+/-10.65) ng.g-1 and (80.06+/-19.14) ng.g-1,
while the amount of MeHg in the corresponding sediment samples was (0.33+/-0.14)
ng.g-1 and (0.50+/-0.19) ng.g-1 for wet and dry seasons, respectively. The ratios
of MeHg/THg in the sediment of the Sanmenxia Reservoir were relatively small in
comparison to those in other aqueous systems, indicating that methylation might
play a minor role in the biogeochemistry of Hg in the Sanmenxia Reservoir. This
might be attributed to the high dissolved oxygen levels of the bottom water and
low organic carbon content of the sediments.
PMID- 29964562
TI - [Identification of Nitrate Sources and Transformation Processes in Midstream
Areas:A Case in the Taizi River Basin].
AB - This study analyzed the nitrate (NO3-), ammonia nitrogen (NH4+-N), chloride (Cl
), delta15 N-NO3-, delta18O-NO3-, and delta18O-H2O in the surface water to
identify the nitrate sources and transformation processes in midstream areas of
the Taizi River basin in May and August 2016, corresponding to the dry season and
wet season, respectively. The results indicated that the NO3-, Cl-, and NH4+-N
concentrations and the delta18O-NO3- in the dry season were greater than those in
the wet season, and the delta15 N-NO3- did not show significant seasonal
variations based on the Man-Whitney U test. The NO3- was derived mainly from the
mixed sources according to the ranges of NO3-/Cl-, delta15 N-NO3-, and delta18O
NO3-. The nitrate sources in the surface water were synthetic fertilizer, soil
nitrogen, manure, and sewage in the Xihe River (XR), Lanhe River (LR), and Xiada
River (XDR) and soil nitrogen and synthetic fertilizer in the Er dao River (EDR)
during the wet season. The sources were synthetic fertilizer and soil nitrogen in
the XDR and soil nitrogen, manure, and sewage in the XR, LR, and EDR during the
dry season. The significant negative relationship between NO3- and NH4+ and the
significant positive relationship between NO3- and delta15 N-NO3- in the wet
season indicated that the volatilization and nitrification of soil N might be
related to NO3- sources in the wet season. NH4+-N and delta15 N-NO3- increased
with decreasing NO3- and Cl- in EDR and LR during the wet season, which indicated
denitrification processes occurred. There was a significant relationship between
NO3- and Cl-, indicating that mixing processes occurred in the surface water
during the two sampling periods. This study will provide a better understanding
for nitrate sources related to seasonal variations and transformation processes
in hilly areas.
PMID- 29964563
TI - [Characteristics of Nitrogen Variation and Its Response to Rainfall:A Case Study
in Wuxi Port at Taihu Lake Basin].
AB - Based on monitoring data of the water quality in the Wuxi port estuary of Taihu
Lake from 2010 to 2015, we studied the temporal variation characteristics of
nitrogen and its response to rainfall in Wuxi port. The results showed that the
pollution level in Wuxi port is serious, with an average annual total nitrogen
(TN) concentration of (4.41-5.92 mg.L-1), worse than the water environment
quality grade V standard (2 mg.L-1). The ammonia nitrogen (NH4+-N) concentration
was 1.09-1.72 mg.L-1. The concentrations of TN and NH4+-N showed obvious seasonal
variations, with the concentration of TN and NH4+-N in summer and autumn higher
than in spring and winter. The concentration of TN in 2015, 2012, and 2011 was
5.92, 5.82, and 5.47 mg.L-1, respectively, which was significantly higher than in
2013 and 2014. The concentration of NH4+-N in 2011 (1.72 mg.L-1) was higher than
in 2013 and 2015. With the increase of rainfall intensity, the TN concentration
showed an increase after the first downward trend and then a decrease, while the
NH4+-N concentration increased first and then decreased. In addition, the
nitrogen concentration in the non-flood season was higher than in the flood
season.
PMID- 29964564
TI - [Dynamics of the Water Quality in a Broad-leaf Evergreen Forest at Different
Spatial Levels on Jinyun Mountain].
AB - A typical forest stand on the subtropical Jinyun Mountain in China was selected
to investigate water quality and interception characteristics for several
important ions at different levels in the subtropical forest ecosystem. Based on
field and laboratory experiments, the effect of precipitation, throughfall,
litterfall, and soil percolation on water quality and ionic interception were
investigated from September 2013 to August 2014. Results indicated that the
rainfall on Jinyun Mountain was obviously acidic, with an average pH of 4.75. The
soil and canopy can elevate the pH of rainfall, while the soil had a greater
capability for adjusting pH than did the forest canopy. In addition, the
concentrations of NH4+, SO42-, PO43-, Mg2+, Ca2+, and K+ in the litterfall
increased with litterfall tissue disintegration, while the other ions decreased.
Moreover, functional groups and colloids in the soil can bind or neutralize many
ions, such as NO3-, SO42-, NH4+, PO43-, K+, and Mg2+. However, some ions were
released from the soil by erosion from acid rain over a long time. Generally, the
forest ecosystem is a sink for ions found in precipitation with diverse functions
for different layers, and the forest canopy has the highest interception capacity
for the ions found in precipitation.
PMID- 29964565
TI - [Method of Improving the Water Quality of Polluted Rivers Based on the MIKE11
Model].
AB - In order to seek ways to improve the quality of polluted rivers, this study
selected the heavily polluted Yinghe River in China for study, as there is a
requirement to improve water quality from the Yangtze River to the Yinghe River.
The permanganate index and ammonia nitrogen are the main pollutant targets for
the Yinghe River. This study applies MIKE11 to set up a one-dimensional model of
the hydrodynamics and water quality using a numerical simulation method to
determine the optimal method for river water quality improvement. The simulation
experiment tests the influence of factors, such as the supplementary water flow,
replenishment water quality, water replenishment position, and method of water
supply to improve the water quality. The simulation results indicate that water
quality improvement can be simulated with the hydrodynamic module (HD) and the
convective diffusion module (AD) combined with the rainfall runoff module (NAM)
in the MIKE11 model. In practice, the option with the best replenishment effect
is to use class III at point 1 and to use class IV at points 2 and 3 when the
supplementary water flow rate is 10% of the river bottom flow. The reduction in
permanganate index and ammonia nitrogen was, respectively, 72.3% and 55.7%, and
over 85% of the study area reached the standard of class IV water quality. This
provides a new method for river pollution control.
PMID- 29964566
TI - [Distribution Characteristics and Risk Analysis of Antibiotic in the Groundwater
in Beijing].
AB - Based on the GC-MS technique, we conducted a survey to investigate the
concentration, distributions, and emission sources of sulfonamides (SAs),
fluoroquinolones (FQs), tetracycline (TCs), beta-lactam, and macrolides in
groundwater in Beijing. Results indicated that SAs, FQs, and TCs were the main
types of antibiotic in groundwater, and the detection ratios of trimethoprim,
ciprofloxacin, and norfloxacin were above 70%. Concentration of antibiotics in
sites from sewage irrigation areas were significantly higher than those from the
drinking source area or the south-to-north water recharge areas. The highest
concentration of sulfadimidine (236 ng.L-1) and sulfadiazine (96.8 ng.L-1) in
groundwater were both found in the sewage irrigation area. An ecological risk
analysis showed a low risk for antibiotic in groundwater at drinking source
sites, while groundwater at sewage irrigation sites fell into the high risk
group. It is important to strengthen the ciprofloxacin monitoring and ensure
underground water safety.
PMID- 29964567
TI - [Characteristics of Carbon and Nitrogen in the Downstream Columnar Sediment of
Maozhou River, Shenzhen].
AB - Based on the determinations of total nitrogen (TN), organic matter (OM), carbon
nitrogen ratio (C/N), delta15 N, and delta13 C on 12 sediment cores, the
distribution characteristics and the sources of nitrogen and organic matter were
analyzed in sediments from the lower reaches and main tributaries of the Maozhou
River. The results showed that the average concentrations of total nitrogen (TN)
and organic matter (OM) were 1815.37 mg.kg-1 and 22 401.68 mg.kg-1, respectively,
in the Maozhou River sediments, which were higher than in TaihuLake and
ChaohuLake. The levels of TN and OM in the study area were high and varied
greatly with the increase of depth. The delta15 N content in the sediments of the
MaozhouRiver downstream ranged from 2.20 0/00 to 32.78 0/00, while the delta13 C
content ranged from -27.53 0/00 to -21.95 0/00. The average concentrations of
delta15 N and delta13 C were 6.78 0/00 and -25.41 0/00. Moreover, the C/N ratio
ranged from 0.49 to -18.23. The delta13 C varied slightly with the increase of
depth, while delta15 N and C/N varied greatly. A source analysis in the study
area indicated that C3 plants and chemical fertilizer were the main sources in
the surface sediments (0-40 cm) downstream of the Maozhou River. Furthermore,
algae were the main sources of organic matter in the deep sediments downstream of
the Maozhou River and in tributary sediments of the Shajing River. Nitrogen in
the surface sediments (0-40 cm) downstream of the Maozhou River mainly comes from
inorganic fertilizer and soil organic nitrogen, while nitrogen in the Maozhou
River deep sediments and Shajing River sediments mainly come from soil erosion
and soil organic nitrogen.
PMID- 29964568
TI - [Relative Importance of Factors Influencing Iron Release in Drinking Water
Distribution Systems].
AB - Iron release in drinking water distribution systems (DWDSs) has attracted
significant attention in recent years. There are many factors influencing iron
release in DWDSs. In this study, we select pH, dissolved oxygen (DO), alkalinity
(Alk), hardness, chloride (Cl-), sulfate (SO42-), temperature (T), and hydraulic
retention time (HRT) as factors to investigate. Stepwise regression and partial
correlation analysis are used as methods for establishing nonlinear power
exponent iron release models and determining the relative importance of these
factors by comparing standardized regression coefficients and partial correlation
coefficients. The results show that the iron release models fit well. The
important factors are SO42-, HRT, Cl-, and T, and the relative importance of the
effect of the factors on iron release is SO42-~HRT > Cl- > T, when measured by
standardized regression coefficients; whereas, the important factors are HRT,
SO42-, Alk, Cl-, and T, and the order of importance is HRT > SO42- > Alk > Cl- >
T, when measured by partial correlation coefficients. Combining these two
results, we conclude HRT, SO42-, and Cl- are the most important factors affecting
iron release in pipes for the conditions in this study. The relative importance
of T and Alk changes depending on the actual situation.
PMID- 29964569
TI - [Removal of High Concentration of Iron, Manganese and Ammonia Nitrogen from Low
Temperature Groundwater Using Single Bio-filter].
AB - A pilot-scale bio-filter was constructed for the removal of high concentrations
of iron (TFe 9.0-12.0 mg.L-1, Fe(II) 6.5-8.0 mg.L-1), manganese (1.9-2.1 mg.L-1),
and ammonia nitrogen (1.4-1.7 mg.L-1) simultaneously from low temperature (5-6C)
groundwater in a plant. The results showed that iron was removed at the beginning
of the bio-filter start-up, and manganese and ammonia nitrogen were removed on
day 72 and day 75, respectively. The start-up period was influenced by the
culture temperature and the raw water quality. For higher filtration rates, the
removal of manganese was lower. When the filtration rate was more than 1.0 m.h-1,
the maximum removal of manganese was about 3.0 mg.L-1. Manganese was the limiting
factor for the increase of filtration rate, and the maximum filtration rate of
the single bio-filter was 4.5 m.h-1. When the filtration rate was less than 6.0
m.h-1, the removal of ammonia nitrogen was about 1.5 mg.L-1, which was not
affected by the filtration rate. Dissolved oxygen (DO) deficiency led to failure
with the removal of more ammonia nitrogen. The required thickness of the bio
filter required for purification increased as the concentration of manganese and
ammonia nitrogen increased when DO was sufficient. The removed iron, manganese,
and ammonia nitrogen move to the depth of the filter layer, and there will be
"manganese dissolution" when the filtration rate is increased. Iron and ammonia
nitrogen in the filter layer can be oxidized and removed simultaneously.
Manganese is oxidized and removed after the iron and ammonia nitrogen. The
effective oxidation and removal section of manganese, iron, and ammonia nitrogen
are obviously graded.
PMID- 29964570
TI - [Mechanism of Pre-ozonation Enhanced Coagulation on DON in the Secondary
Effluent].
AB - Municipal wastewater effluent is increasingly used as reclaimed water and source
water for downstream areas. Scholars are beginning to study the potential of
dissolved organic nitrogen (DON) as a precursor to the formation of nitrogen
disinfection by-products (DBP). In order to explore the mechanism of pre
ozonation coupled with enhanced coagulation on DON in the secondary effluent, the
distributions of molecular weight and hydrophobicity/hydrophilicity of DON were
analyzed. Disinfection by-product formation potential from chlorination was also
investigated. Lastly, the composition and chemical structure of DON before and
after coagulation were studied in combination with 3DEEM. Our results showed that
pre-ozonation followed by coagulation with PACl significantly enhanced the
removal of DON and mitigated DBP formation potentials. The following conclusions
can be drawn from this study:1 The tested effluent was very hard as indicated by
total hardness and high calcium concentrations, and the pH had an important
effect on pre-ozonation enhanced coagulation. As pH was decreased, the rates of
DON, DOC and UV254 removal increased. At pH 6.2, the rate of DON removal was
maximal, and a 3.7 fold increase in removal-rate was achieved. 2 Calcium played a
critical role in pre-ozonation enhanced coagulation. Zeta potentials and calcium
concentrations were substantially affected at higher ozone doses. At ozone dosage
of 8 mg.L-1, Zeta potentials increased from -33 to -8 mV, and calcium
concentrations decreased from 116 to 89 mg.L-1. The ratio of calcium hardness to
DOC was relatively high in this study, approaching 24 mg.mg-1 (CaCO3/DOC). Thus,
pre-ozonation promoted the removal of DON by coagulation. 3 Large molecular
weight and hydrophobic DON were easier to remove by coagulation. Ozonation
modified the DON characteristics to become more hydrophilic and smaller in
molecular weight. Coagulation reduced overall DBP formation potentials to less
than 20%. Pre-ozonation enhanced coagulation decreased overall DBP formation
potentials by more than 45%. 4 Finally, the 3DEEM spectra indicated that the
formation potentials and DON characteristics, due to disinfection, were related
to three main peaks, which corresponded to tryptophan-based proteins, aromatic
proteins, and fulvic acids.
PMID- 29964571
TI - [Base Activation of Peroxymonosulfate for the Degradation of Ciprofloxacin in
Water].
AB - The degradation of ciprofloxacin (CIP) in a base activated peroxymonosulfate
(PMS) system was investigated. Results showed that a base activated PMS system
can efficiently remove CIP. Singlet oxygen (1 O2) and superoxide anion radical
(O2-.) were confirmed to be the major reactive oxygen species through radical
quenching experiments. The NaOH concentration, PMS concentration, reactive
temperature, and coexisting anions also affected CIP removal. Both NaOH and PMS
concentration presented a dual effect, which was highly concentration dependent.
An improvement in reactive temperature accelerated CIP degradation, and the
calculated activation energy (Ea) was determined to be 5.09 kJ.mol-1 through the
fitting of the Arrhenius equation. Different anions had different effects on CIP
degradation. No obvious change in CIP concentration was observed when Cl-, SO42-,
and NO3- were introduced. H2PO42- inhibited the degradation, but CO32-
significantly promoted it. Ten oxidation products were identified through UPLC
MS/MS analysis, and the piperazine ring in the molecular structure of CIP was
preferentially attacked by reactive oxygen species in the base activated PMS
system.
PMID- 29964572
TI - [MIL-88A@MIP Activated Persulfate for Targeted Degradation of Dibutyl Phthalate].
AB - MIL-88A@MIP was fabricated for the first time in this experiment with a metal
organic framework of MIL-88A as the precursor based on the molecular imprinting
method. It was characterized by X-ray diffraction (XRD), scanning electronic
microscopy (SEM), energy dispersive spectrometer (EDS), and N2 adsorption. The
catalytic performance of MIL-88A@MIP was tested to activate persulfate (PS) to
generate SO4-. for the degradation of dibutyl phthalate (DBP), which was used as
a target pollutant. Compared with the precursor MIL-88A, the catalytic activity
of MIL-88A@MIP was improved effectively through targeted modification, and the
DBP removal rate increased 80.4% after reacting for 480 min. An experiment
determining the influencing factors showed that the optimum activation condition
of the catalyst was PS:DBP=600:1, MIL-88A@MIP dosage of 0.5 g.L-1,and pH=3.26.
Furthermore, MIL-88A@MIP shows a high capability of removing different phthalic
acid ester (PAE) contaminants that reflect its targeting selectivity.
PMID- 29964573
TI - [Methane Cycle Anaerobic Membrane Bioreactor with Desulfurization for Treating
High Sulfate Organic Wastewater at Normal Temperature].
AB - The operational performance of a methane cycle anaerobic membrane bioreactor
(MCAnMBR) with desulfurization for the treatment of high sulfate organic
wastewater was investigated. Within 63 days, the MCAnMBR with desulfurization was
started successfully at a normal temperature of 26-34C. The two main problems at
the beginning of debugging, sludge loss and increased pH, were effectively solved
by adjusting the gas path system and adding methanol to the inflow for
acclimation. The results show that the inflow concentration of SO42- from 650
mg.L-1to 5800 mg.L-1can be treated well with the conditions of hydraulic
retention time (HRT)=120 h, a volume loading of 3.61-4.36 kg.(m3.d)-1, pH of 7.18
7.61, and temperature of 23.3-25.4C. The effluent chemical oxygen demand (COD)
concentration could be lowered to 23 mg.L-1. The total removal rate of COD could
remain stable at 96.23%-99.77%, and the SO42- conversion rate was about 83.83%
95.51%. These results indicated that the MCAnMBR reactor with desulfurization
could effectively solve the problem of secondary sulfide inhibition. A gradient
experiment revealed that the high Na2SO4 inflow could be treated when the
influent COD ranged from 18000 mg.L-1to 21000 mg.L-1, the concentration of SO42-
ranged between 9082 mg.L-1 and 9600 mg.L-1, and the COD/SO42-=2.
PMID- 29964574
TI - [Simultaneous Recovery of Nutrients from Wastewater by Mesoporous MgO-loaded
Natural Zeolital].
AB - Using MgO modified natural zeolite (NZ-MgO) as a settling agent, nutrients from
synthetic contaminated waters were recovered as a struvite precipitate. Different
reaction conditions, including reagent dosage, solution pH, contact time, and
coexisting calcium ions, were investigated. In order to understand the recovery
mechanism, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction
(XRD) were utilized to analyze the chemical composition of recovered
precipitates, and Brunauer-Emmett-Teller (BET) and field-emission scanning
electron microscopy(SEM) were used to detect the surface area and morphology. The
results showed that NZ-MgO exhibited a strong removal capacity, with a maximum
removal capacity of 119.2 mg.g-1 for phosphate and 48.5 mg.g-1 for ammonium
nitrogen at a dosage of 0.4 g.L-1, initial pH of 7, and contact time of 2 h. The
kinetics of both phosphate and ammonia nitrogen followed the pseudo-second-order
kinetic model (R2>0.99), which revealed that the chemical process occurred at the
solid-liquid interface. The mechanisms for nutrient recovery by NZ-MgO were
struvite crystallization, physical adsorption, ion exchange, and electrostatic
attraction, with struvite crystallization being the main mechanism. Existing
calcium ions would hinder the simultaneous recovery of nutrients from wastewater,
resulting in a struvite decline and calcium phosphate increase.
PMID- 29964575
TI - [Phosphorus Removal Capacity of Domestic Wastewater Treated by a Modified CAST
Process Under Different Operating Modes].
AB - A modified cyclic activated sludge technology (CAST) treating domestic wastewater
was employed to investigate the effects of different operating modes, such as C/P
ratio, reflux ratio, and temperature on phosphorus removal. The results
illustrated that at room temperature the phosphorus removal of the system
improved significantly when the influent C/P ratio increased from 50 to 100, with
the removal efficiency increasing rapidly from 15% to 95.6%. Decreasing the C/P
ratio to 75, the phosphorus removal performance declined due to influent carbon
source deficiency, and the mean phosphorous removal efficiency decreased to
51.4%. At the same time, the long-term addition of an easily degradable carbon
source resulted in sludge bulking and a large amount of sludge loss. With a low
C/P ratio, the phosphorus removal performance increased by 2.3 times when the
sludge reflux ratio decreased from 25% to 12.5%. However, the phosphorus removal
performance declined when reducing it to 0. The temperature experiment results
showed that the phosphorous removal efficiency of the system remained stable,
above 90%, in the low temperature system (14C+/-1C). However, the phosphorous
removal efficiency of a shortcut nitrification system at high temperature (27C+/
1C) was only 14.1%, suggesting that a low temperature was beneficial for removing
phosphorous. It was observed from the batch tests that the sludge at room
temperature could utilize dissolved oxygen, nitrate, and nitrite as electron
acceptors to take up phosphate. The sludge in the low temperature system could
use both dissolved oxygen and nitrate as the electron acceptors. However, the
sludge in the high temperature system could only use dissolved oxygen as the
electron acceptors to take up phosphate. In addition, it was also found that
sludge under starvation conditions resulting from short-term idling of the system
favored phosphorus removal.
PMID- 29964577
TI - [Substrate Inhibition and Kinetic Characteristics of Marine Anaerobic Ammonium
Oxidizing Bacteria Treating Saline Wastewater].
AB - An anaerobic sequencing batch reactor (ASBR) was used to study substrate
inhibition and kinetic characteristics of marine anaerobic ammonium oxidizing
bacteria (MAAOB) treating saline wastewater. The results indicated that when
ammonia increased to 1200 mg.L-1, the MAAOB still maintained good nitrogen
removal capability, though there was a slight inhibitory effect. At the same
time, nitrite nitrogen removal efficiency was stable at about 80.70%. When
nitrite increased to 265.6 mg.L-1, the MAAOB were inhibited obviously, and
ammonia nitrogen removal efficiency decreased to about 63.01%. When influent
nitrite concentration increased to 305.6 mg.L-1, the removal rate of ammonia
nitrogen further decreased to 43.93%. The kinetic characteristics resulting from
inhibition of the MAAOB were simulated by the Haldane model and Aiba model. Three
parameters, TNRRmax, KS, and Ki, and the relationship between effluent substrate
concentration and total nitrogen loading (TNRR) were evaluated. Based on further
analysis, the Haldane model was more suitable for describing dynamic
characteristics resulting from NH4+-N inhibition, while the Aiba model was more
suitable for describing the dynamic characteristics resulting from NO2--N
inhibition. The predicted effluent inhibitory concentrations of NH4+-N and NO2--N
were 3893.625 mg.L-1 and 287.208 mg.L-1, respectively. The results could provide
a theoretical basis for saline wastewater treatment by MAAOB.
PMID- 29964576
TI - [Realization of Shortcut Nitrification in the ABR-MBR Process Treating Domestic
Wastewater].
AB - The operational control conditions for realizing shortcut nitrification in the
membrane bioreactor (MBR) process was investigated in a lab-scale anaerobic
baffled reactor (ABR)-MBR combined system, which laid the foundation for further
research on the performance of denitrification phosphorus removal in the system.
The experimental results under different conditions showed that shortcut
nitrification in the MBR was achieved by controlling the dissolved oxygen (DO)
concentration to low levels (0.5-1.0 mg.L-1 to 0.3-0.7 mg.L-1) and changing the
effective volume of the MBR to control hydraulic retention time (HRT), with the
HRT in the ABR equal to 6 h, sludge reflux ratio of 100%, NOx--N reflux ratio of
300%, and temperature of 30C+/-2C. Finally, the shortcut nitrification
deteriorated as the HRT in the MBR increased from 3 h to 5 h, with nitrite
accumulation rate dramatically dropping from 60% to 15%. The analysis of the
influencing factors of shortcut nitrification showed that maintaining low DO
concentration (0.3-0.7 mg.L-1) and gradually shortening HRT were the key factors.
The pH, free ammonia (FA), free nitrous acid (FNA), temperature, and sludge
retention time (SRT) had a slightly positive effect on shortcut nitrification.
During the period of shortcut nitrification, a stable and high efficiency removal
of COD and NH4+-N were achieved, and the average concentration of the effluent of
COD and NH4+-N, whose removal rates were above 90%, were below 50 mg.L-1 and 2
mg.L-1, respectively, and the removal efficiency of total nitrogen (TN) reached
72%.
PMID- 29964578
TI - [Effect of Free Ammonia on Ammonia Escape During an Ammonia Oxidation Process].
AB - This study used short process nitrification sludge to investigate the effect of
high free ammonia (FA) on ammonia escape during ammonia oxidation. A sequencing
batch reactor (SBR) was used to study the ammonia escape process under different
FA concentrations. The results indicate that FA in water is usually combined with
water molecules at lower FA concentrations to produce stable NH3.H2O with almost
no ammonia escape. With high FA concentration (FA>687.1 mg.L-1), ammonia nitrogen
is not oxidized to oxidized nitrogen (NO2--N concentration is <0.1 mg.L-1 at the
end of aeration), but the total nitrogen (TN) reached 269.7 mg.L-1. Therefore,
when there is a high FA concentration, NH4+-N will evaporate in the form of FA,
resulting in ammonia escape. In addition, when 226.6 <= FA <= 711.8 mg.L-1, the
free ammonia escape rate (FEV) grows rapidly with the increase in FA
concentration.
PMID- 29964579
TI - [Water Quality and Diversity of Denitrifier Community Structure of Typical Scenic
Water Bodies in Xi'an].
AB - Six micro-polluted landscape water bodies were selected to explore the
relationship between water quality and the nirS-Type denitrifier community
structure and diversity with an Illumina high-throughput sequencing technique.
The results of a physico-chemical analysis of the water bodies showed that the
Fengqing Park (FQ) and Laodong Park (LD) water bodies were classified as inferior
V water quality, the Qujiang Park (QJ), Mutasi Park (MTS), and Xinjiyuan Park
(XJY) water bodies were classified as V water quality, and the Yongyang Park (YY)
water quality was classified as IV. The TN values varied from 1.21 mg.L-1 to 6.50
mg.L-1, with the lowest value found in YY and the highest in FQ (P<0.05). TP was
significantly higher in LD (0.10 mg.L-1) and significantly lower in QJ[0.02 mg.L
1 (P<0.05)]. The NH4+-N in LD was 4.44 times higher than that in QJ and FQ
(P<0.01). Illumina high-throughput sequencing revealed that the denitrifier
community composition was significantly different among the six water bodies, and
Paracoccus sp., Pseudomonas sp., and Rubrivivax sp. were the dominant genus
species. A principle component analysis (PCA) indicated that the nirS-Type
denitrifier communities of XJY and MTS were mainly regulated by NH4+-N and the
permanganate index, LD and FQ were significantly influenced by NO3--N, NO2--N,
TN, TP, and DO, and YY was significantly influenced by pH value. Our results
showed that nirS-Type denitrifier communities were regulated by different water
quality indicators.
PMID- 29964580
TI - [Start-up and Characteristics of the Microbial Community Structure of ANAMMOX].
AB - An anaerobic ammonium oxidation (ANAMMOX) reactor was successfully started up in
17 days, with the up-flow anaerobic sludge blanket (UASB) reactor being seeded
with mixed anaerobic sludge from laboratory cultures with an ANAMMOX function and
aerobic activated sludge from a municipal sewage treatment plant in a volume
ratio of 1:2. The processes could be divided into two phases of hydrolysis,
enhanced and steady. Anaerobic ammonium oxidation bacteria (AAOB) were enriched
by improving the reactor volume load gradually after the steady phase. When the
volume load increased from 0.10 kg.(m3.d)-1 to 0.44 kg.(m3.d)-1, the removal of
total nitrogen (TN) also increased from 0.09 kg.(m3.d)-1 to 0.42 kg.(m3.d)-1. The
color of the sludge changed from a light red that deepened gradually in the UASB
reactor. At that time, the proportion of the sludge particle size greater than
0.2 mm increased from 10.90% to 38.37%.The sludges from the inoculation phase and
from the phase when the volume load was increasing were analyzed by high
throughput sequencing, indicating that Chloroflexi, Proteobacteria, WWE3,
Actinobacteria, Planctomycetes, and so on were the dominant species. The
proportion of Proteobacteriain the denitrification bacteria was gradually reduced
from 21.60% to 14.20% with an increase in the degree of AAOB enrichment, while
the Planctomycetes increased from 0.73% to 15.50%. Candidatus Brocadia,
Candidatus Jettenia, and Candidatus Kuenenia were the main species of
Planctomyceteswhen the volume load increased to 0.44 kg.(m3.d)-1 in the reactor,
and the Candidatus Brocadia was the main species of AAOB, which accounted for
13.40%.
PMID- 29964581
TI - [Fast Start-up and Performance of the CANON Process Based on a SBAF Systemand
Evolution Properties of Microorganisms].
AB - The CANON process has the disadvantages of long start-up periods and unstable
operation. In the SBAF system, under strictly controlled conditions of dissolved
oxygen (DO) and temperature, a CANON process is started up in 51 days and is
operated stably for 278 days using a new method of independent research and
development. The results show that the maximum and average ARR are 98.9% and
95.1%, respectively. The maximum and average TNR are 85.9% and 75.1%,
respectively. Furthermore, a small quantity of nitratenitrogen exists in this
system. The microbial structure features of the sludge are analyzed by 16S rDNA
macro high-throughput genome sequencing. It is verified that Proteobacteria is
the main microorganism in the AOB, and Planctomycete Candidatus Brocadia is the
main microorganism in the AnAOB. Both of them collaborate on total nitrogen
removal in the CANON process.
PMID- 29964582
TI - [Enrichment of Nitrospira in Activated Sludge and Kinetic Characterization].
AB - Nitrospira was enriched from activated sludge by using fed-batch cultivation, and
its related kinetic characterization was studied. The results showed that
Nitrospira could be successfully enriched from the activated sludge for a
controlled nitrite concentration no higher than 2 mg.L-1. The maximum nitrate
oxidation rate was 48.72 mg.(g.h)-1. The fluorescence for the in situ
hybridization results showed that Nitrospira accounted for about 75% of the total
biomass, while Nitrobacter accounted for only 0.1%. In addition, the kinetic
parameters of Nitrospira at 20C were also investigated. The results showed that
the optimum growth temperature for Nitrospira was 30-35C. The temperature
correction coefficient tauN was 1.046. The nitrite half-saturation constant KS
and oxygen half-saturation constant KO were (0.32+/-0.03)mg.L-1 and (1.52+/
0.09)mg.L-1, respectively. This study on the kinetic characterization of
Nitrospira provided a theoretical foundation for the treatment plant design and
process optimization.
PMID- 29964583
TI - [Effect of pH Value on Autotrophic Denitrification Process of Zero Valent Iron
Substrate].
AB - Using a substrate with zero valent iron and nitrate, the research determined the
change of pH value in the iron autotrophic denitrification process and the effect
of pH on zero valent iron autotrophic denitrification activated sludge using
batch experiments and a continuous flow fermenter denitrification rate. Batch
experiments were carried out with four reactor bottles with sludge addition. The
initial pH values were 6.2, 6.7, 7.5, and 8.8, respectively, and there was an
initial pH of 6.7 in a bottle without sludge addition. The results showed that
the initial pH value of 6.7 obtained the highest nitrogen removal rate. For the
bottle without sludge addition, the pH rose to about 10. The pH value of the four
batch experiments was concentrated between 7.5-7.8 in the follow-up process, so
there was no significant difference in the effects of pH on denitrifying
bacteria. However, the pH value in the fermenter can be controlled stably by an
acid-base pump. With five pH gradients of 6, 6.5, 7, 7.5, and 8, the adaptability
and activity of microorganisms under a constant pH value were observed
separately. The sludge activity was the highest at pH 6.5, and the highest
nitrogen removal rate was 1.35 mg.(L.h)-1.
PMID- 29964584
TI - [Effect of Seeding Single/Mixed Sludge on Rapid Start-up of an ANAMMOX Reactor].
AB - The experiment explored the effect of different seeding sludge on the rapid start
up of an anaerobic ammonium oxidation (ANAMMOX) reactor by seeding a single type
of denitrified granular sludge and a mixed sludge composed of denitrified
granular sludge and aerobic nitrification sludge (the volume ratio of the mixed
sludge was 2:1) in two sequencing batch reactors (SBR), R0 and R1, respectively.
The results indicated that R0 was started up successfully on day 64 with a
nitrogen removal rate (NRR) of 0.26 kg.(m3.d)-1, while R1 was started up by day
47 with a NRR of 0.30 kg.(m3.d)-1, which was shorter than R0 by 17 d. In the
enrichment stage, reddish sludge appeared in R1, and the characteristics of
anaerobic ammonium oxidation of the system were more obvious than in R0. After
the reactor was started up successfully, the stoichiometric ratio of R0 was 1.20
and 0.34, respectively, and the stoichiometric ratio of R1 was 1.26 and 0.21,
which was closer to the theoretical values of 1.32 and 0.26. The mixed liquor
suspended solids (MLSS) and mixed liquor volatile suspended solids (MLVSS) of R0
were restored to 51% (4.2 g.L-1) and 38% (2.3 g.L-1)of the initial seeding
sludge, respectively, while the MLSS and MLVSS of R1 were restored to 54% (4.4
g.L-1) and 42% (2.6 g.L-1),which was higher than R0. It can be speculated that
the proliferation rate of AnAOB in R1 was faster than in R0. Seeding mixed sludge
can accelerate the start-up process of anaerobic ammonium oxidation with more
stable N-removal performance.
PMID- 29964585
TI - [Comparison of Start-up and Stable Performance of Nitritation in Activated Sludge
and Biofilm Processes in a SBR].
AB - This study investigates the effect of increased hydraulic retention time (HRT)
and dissolved oxygen (DO) on the destruction and restoration of the performance
of activated sludge and biofilm sequencing batch reactor (SBR) nitritation after
the processes were simultaneously started up and stably operated at room
temperature (25C). The results showed that was easier to start nitritation in an
activated sludge reactor, but nitritation was destroyed when DO was 2-2.5 mg.L-1.
The performance could be restored by reducing DO to 0.5-1 mg.L-1. The biofilm
process was not affected by DO. Prolonging HRT destroyed the stable operation of
the two processes. Compared with the method of biofilm, the activated sludge
method had less resistance, but restoring performance was better than for the
biofilm process after shortening the HRT. Subsequently, the temperature (20, 15,
and 10C) was continuously reduced to investigate the synergistic effect of DO and
temperature on nitritation stabilization. The results showed that the reduction
of temperature destroyed the stable operation of nitritation, but the reduction
of DO concentration could compensate for the adverse effects of temperature
reduction. In addition, when the temperature was higher than 20C, the rate of
nitritation in the activated sludge process was better than that in thebiofilm
method. At low temperature (below 15C), a stable operation of nitritation was
easier to achieve with the biofilm method. The capacity of the activated sludge
process was hardly changed at 10C. The above conclusions were confirmed by
molecular microbiological analysis, and it was found that the stable operation of
nitritation could be achieved without complete wash-out of the nitrite-oxidizing
bacteria (NOB).
PMID- 29964586
TI - [Long-term Impacts of TiO2 Nanoparticles on the Stability of an Anaerobic
Granular Sludge Bioreactor].
AB - In the present study, the fate and long-term effect of TiO2 nanoparticles (NPs)
on anaerobic granular sludge (AGS) was evaluated in an anaerobic methanogenic
system. In the short-term experiment, the methane production rate decreased when
the dosage of TiO2 NPs was greater than 150 mg.g-1. However, no significant
difference in the products of acidification and methanation between the control
and 150 mg.g-1(as VSS) of TiO2 NPs assays was observed, indicating low bacteria
cytotoxicity of TiO2 NPs on AGS in dark anaerobic digestion. The operation data
of the AGS bioreactor showed that acidogens was more sensitive to prolonged
exposure to TiO2 NPs with the accumulation of VFAs and a decrease of biogas
production in the TiO2 NPs containing reactor. The inhibiting effect of TiO2 NPs
on the AGS might be attributed to the physical restraints. The average TiO2
concentration escaping with the effluent was 0.632 mg.L-1, suggesting most of the
NPs were retained inside the reactor. The long-term presence of TiO2 NPs could
alter the composition of the microbial communities in the AGS, since the amount
of Methanosarcina increased by 115.6%. The results also indicated that the
treatment of short-term sudden exposure to TiO2 NPs using batch tests might not
be appropriate for interpreting their cumulative effects on the AGS, since a long
time was need for the TiO2 NPs to show negative effects on the microbial
populations in the AGS. Our study could supply useful proof for assessments of
potential risks for TiO2 NPs on anaerobic activated sludge.
PMID- 29964587
TI - [Composition and Distribution of Antibiotics in Soils with Different Land Use
Types in a Typical Peri-urban Area of the Yangtze River Delta].
AB - Antibiotics have been widely used for agriculture, aquaculture, and livestock, as
well as for human disease treatment, in recent decades. However, antibiotics
cannot be completely absorbed, and most of them are excreted through urine and
feces. A substantial part of the antibiotics enter soils through fertilization
and irrigation. Antibiotics persist in the soil environment and threaten human
and ecological security. Identifying the composition, distribution, and factors
affecting antibiotics in soils with different land use types can help in
understanding the spatial distribution and migration processes of antibiotics. In
this study, a typical peri-urban catchment located in the Yangtze River delta was
selected as the study area, and 82 sampling sites were selected based on land use
and topographical features. Soil samples were collected at depths of 0-40 cm at
each sampling site. The types and quantity of antibiotics in each soil sample
were identified and analyzed by using HPLC-MS/MS in the laboratory. The
composition and concentration of antibiotics in different soil layers and the
land use types were compared, and the factors affecting the spatial distribution
of soil antibiotics were analyzed. Results from this study showed that the total
concentration of antibiotic compounds (total) ranged from 0.05 MUg.kg-1 to 395.55
MUg.kg-1 in the study area, and a significant spatial distribution of antibiotics
was found between different land use types. The total in cropland ranged from
0.35 MUg.kg-1 to 395.55 MUg.kg-1, and tetracyclines (TCs) were the dominant
antibiotics (81.45%). The total in forestland ranged from 0.07 MUg.kg-1 to 3.65
MUg.kg-1, with values significantly lower than those in cropland (P<0.05). The
total in orchard soil were significantly lower than in cropland (P<0.05), and no
significant differences in antibiotics were found between orchards and forestland
(P>0.05). The analysis of the composition and quantity of antibiotics in the
soils showed that tetracyclines (TCs) and quinolones (QNs) were the dominant
antibiotic types in orchards (TCs:67.63%, QNs:29.55%) and forestland (TCs:13.25%,
QNs:70.04%). The indices, including distance to town, distance to road,
elevation, and C/N value in soils, were selected to explore the influence of
human activity on soil antibiotic concentration. Results of the correlation
analysis showed that the concentration of soil antibiotics decreased with
increasing values of the four indices. This indicated that the concentrations of
soil antibiotics in peri-urban areas were dominantly affected by land use and its
spatial distribution, and the concentrations increased with the intensity of
human activities. Results of this study can provide scientific guidance for soil
management and soil security.
PMID- 29964588
TI - [Distribution of Phosphorus in Soil Profiles after Continuous Application of
Different Fertilizers].
AB - This study clarifies the distribution and migration characteristics of phosphorus
in the soil profile and discusses the phosphorus load of farmland after
continuous application of different organic fertilizers. The distribution and
migration characteristics of phosphorus in soil profiles were studied through a
field experiment lasting four consecutive years. The results showed that total
phosphorus and Olsen-P are mainly accumulated in the soil surface, and their
contents decrease with the deepening of soil depth after the continuous
application of different fertilizers. With a four-year application of higher
levels of organic fertilizer, the total phosphorus was found to migrate into the
15-30 cm soil layer. Olsen-P was found to migrate into the 60-90 cm soil layer
under higher levels of pig manure. The ratio of available phosphorus to total
phosphorus in the soil surface increased, and there were significant differences
after the application of different amounts of organic fertilizers. The amount of
Olsen-P as a proportion of total phosphorus in the soil profile decreased as pig
manure treatment > chicken manure treatment > sludge treatment > phosphate
fertilizer treatment. After the application of chicken manure, pig manure,
sludge, and phosphate fertilizer, the value of Olsen-P in the soil surface
increased with an increase in phosphorus input and then remained stable. When
applying the same phosphorus onto the soil, the contribution of different organic
fertilizers to Olsen-P in the surface soil was quite different. The
bioavailability and mobility of phosphorus from pig manure was significantly
higher than that of chicken manure, sludge, and phosphate fertilizer.
PMID- 29964589
TI - [Occurrence of Organophosphate Esters in Soils of the Three Gorges Reservoir].
AB - Organophosphate esters (OPEs) were first identified and quantified in farmland
and riparian soil in the Three Gorges Reservoir (TGR) of western China. The mean
concentrations of OPEs were 272 ng.g-1 dry weight (dw) in farmland soil and 498
ng.g-1 dw in riparian soil. These values lie at the middle of the range of
worldwide values. Hydrodynamic conditions might be important factors contributing
to the slightly different spatial distribution of the OPEs. The concentrations of
the OPEs in riparian soil exceed those in farmland soil, which could partly be
ascribed to the operation of the Three Gorges Dam (TGD). Of particular note is
the elevated contribution of TCP, followed by EHDPP, accounting for more than 90%
of the total OPEs, and the degradation of TBEP by microorganisms in the soil
could be related to the low occurrence of TBEP. Significant correlation between
the OPE concentrations in farmland and riparian soil were obtained, indicating
that the OPEs in farmland and riparian soil originated from the same source. A
principal component analysis (PCA) showed that the OPEs in farmland soil might
come largely from construction and decoration materials, and the OPEs in riparian
soil may be derived from a combination of construction materials and vehicular
traffic emissions.
PMID- 29964590
TI - [Pollution Characteristics, Source Analysis and Potential Ecological Risk
Assessment of Heavy Metals in Soils Surrounding a Municipal Solid Waste
Incineration Plant in Shanghai].
AB - The contents of ten heavy metals (As, Cu, Cd, Cr, Pb, Ni, Zn, Ti, Mn, and Hg)
were determined in the surface soils surrounding a municipal solid waste
incineration plant in Shanghai using atomic spectroscopy. The spatial
distribution and sources of the detected heavy metals were studied by enrichment
factor and multivariate statistical and spatial interpolation analyses. In
addition, their potential ecological risk was assessed. The results showed that
all heavy metals, except Hg and As, were detected with mean contents ranging from
0.399 to 4220 mg.kg-1. The mean contents of Cu, Cd, Cr, Pb, Ni, Zn, and Mn were
higher than their respective background values in Shanghai. In particular, the
mean content of Cd was 2.9 times its background value. The results of the
Pearson's correlation, principle component, enrichment factor, and spatial
distribution analyses of these heavy metals indicated that Ti, Mn, and Ni
primarily originated from natural sources, while Cd, Cr, Cu, Pb, and Zn
originated from industrial manufacturing, combustion, and traffic emissions. The
potential ecological risk assessment showed that soils surrounding the municipal
solid waste incineration plant suffered from a moderate-level risk. The mean
value of the potential ecological risk index of these detected heavy metals was
108.92, of which Cd contributed as high as 79.63%, deserving much attention.
PMID- 29964591
TI - [Comparison of Characteristics and Source Apportionment of Polycyclic Aromatic
Hydrocarbons in Different Environmental Media in the Urban Area of Daqing City].
AB - In order to investigate the various pollution characteristics and sources of
polycyclic aromatic hydrocarbons (PAHs) in different environmental media, 23
street dust samples and four soil samples were collected in October 2012 in
Daqing City. After extraction by Dionex ASE300 and purification, the content of
the US EPA priority pollutants[16 individual PAH and total PAHs (SigmaPAHs)] was
determined by using gas chromatography-mass spectrometry (GC/MS). The results
showed that the range of SigmaPAHs content in street dust was 579.5-4656.7 ng.g
1, and the average content was 1839.7 ng.g-1. The mass percentage of PAHs in the
street dust in different functional areas in Daqing showed a similar mass ratio
range, with the average mass percentage of low ring (2-3 rings) PAHs of 37.9%,
medium ring (4 rings) PAHs of 37.3%, and high ring (5-6 rings) PAHs of 24.8%.
However, low ring PAHs, with mass ratios of 69.3%-99.97%, overwhelmingly
dominated the Daqing soil, Daqing lake sediment, Daqing lakes, and Daqing ponds
(data from literature). The distribution of SigmaPAHs content was not significant
among different functional areas and was closely related to the type of the
plants around the sampling sites. The isomer ratio method confirmed that the
sources of PAHs in the street dust in the study area were mixed sources,
including oil spills, fuel oil combustion, and coal/biomass burning. Positive
matrix factorization (PMF) results showed that the PAHs in the street dust in the
center of Daqing originated from coal combustion, oil spill sources, industrial
sources, and traffic sources, with contribution rates of 30.1%, 26.9%, 23.6%, and
19.3%, respectively, which were not exactly the same trend as that in other
media.
PMID- 29964593
TI - [Distribution Characteristics and Health Risk for Heavy Metals in Vegetables Near
the Industrial Areas in Shanghai].
AB - The concentrations of Cd, Zn, Pb, Cu, Hg, and As in vegetables collected from the
industrial areas in suburban Shanghai were analyzed before and after washing.
Results showed that the average concentrations (fresh weight) of Cd, Zn, Pb, Cu,
Hg, and As in washed vegetables were 0.023, 4.444, 0.112, 0.826, 0.004, and 0.094
mg.kg-1, respectively. Amaranth accumulated the highest Cd, Zn, Pb, and Cu, while
pakchoi accumulated the highest Hg and As. There was no significant difference of
heavy metals between different sites. Washing vegetables prior to cooking reduced
the health risk for heavy metals related to the consumption of vegetables. A
health risk evaluation indicated that more than 55% of the Total Target Hazard
Quotient (TTHQ) came from As, while the other elements contributed less than 1,
indicating that the health risk from vegetable consumption was mainly caused by
As. Children have higher health risks than adults when eating the same
vegetables.
PMID- 29964592
TI - [Magnetic Response of Heavy Metal Pollution in Playground Dust of an Industrial
Area].
AB - The use of mineral magnetic measurements as a potential pollution proxy is
explored as an alternative means of monitoring heavy metal pollution in
playground dust in industrial areas. Dust samples were collected from playgrounds
in an industrial area in Nanjing. The magnetic properties of the samples were
analyzed, and the total and acid-extractable concentrations of heavy metals were
measured.Mineral magnetic concentration parameters[mean magnetic susceptibility
(chilf) 939.31*10-8 m3.kg-1 and saturation isothermal remanent magnetization
(SIRM) 16618.74*10-5 A.m2.kg-1] indicate that the dust samples contain high
concentrations of magnetic minerals when compared to the non-industrial zone of
the city. High and stable S-ratio values (mean 0.97, standard deviation 0.01)
indicate the prominence of ferromagnetic minerals. Low values of anhysteretic
remanent magnetization (chiARM)/chilf(2.35) and chiARM/SIRM (0.12*10-3 m.A-1)
indicate predominantly coarse pseudo single domain (PSD) and multi-domain (MD)
magnetic grain size assemblages. The playground dust is considered moderately to
highly polluted, and the enrichment factor values for Cd, Zn, Cu, and Pb indicate
extremely high contamination levels in the playground dust. Mineral magnetic
parameters[chilf, SIRM, hard isothermal remanent magnetization (HIRM), chiARM,
and chiARM/SIRM] reveal significant correlations with total and acid-extractable
concentrations of the trace metals, and the correlations with total
concentrations are stronger. The most significant correlations were found with
mineral magnetic concentrations (chiARM and SIRM) and total concentrations of the
elements Mn, Ni, and Cr and the Tomlinson pollution load index (PLI) (0.69 <= r
<= 0.86, P<0.01). Consistent spatial characteristics between them were also
found, showing that the total concentrations of heavy metals and magnetic
parameter values are higher in the playgrounds near and downwind of the power
plant. Results of a principal component analysis indicate that anthropogenic
activities (mainly from coal consumption by power plants) are the main sources
for both heavy metals and magnetic minerals. In summary, significant correlations
and consistent spatial characteristics between heavy metal contents and magnetic
parameters and the same anthropogenic source for heavy metals and magnetic
minerals confirm that magnetic parameters could be considered as efficient
indicators for heavy metal contamination in the playground dust in industrial
areas.
PMID- 29964594
TI - [Impacts of Silicon Fertilizer as Base Manure on Cadmium Bioavailability in Soil
and on Cadmium Accumulation in Rice Plants].
AB - The impacts of silicon (Si) on cadmium (Cd) bioavailability in soil and Cd
accumulation in rice plants were investigated in pot experiments with rice (Oryza
sativa L.) cultivation. Silicon fertilizer as the base manure (Si 0, 15, 30, and
60 mg.kg-1) was added in simulated slightly Cd-contaminated soil (total soil Cd
of 0.72 mg.kg-1) and severe Cd-contaminated soil (total soil Cd of 5.08 mg.kg-1).
It indicated that the application of 15-60 mg.kg-1 Si before the rice was
transplanted improved soil pH values and reduced the contents of exchangeable-Cd
and TCLP extractable-Cd in the soil by 24.2%-43.7% and 12.7%-46.8%, respectively,
during the rice growing stages. The reduction in soil Cd bioavailability resulted
from the complexing of Si and Cd, and the reduction followed the order:slightly
Cd-contaminated soil > severely Cd-contaminated soil. It was obvious that silicon
fertilizer improved rice biomass above ground, especially for rice grain yield.
In the slightly Cd-contaminated soil, Si both promoted and restrained soil Cd
transportation from the rice root to the shoot; the low application (Si 15 mg.kg
1) and high application (Si 60 mg.kg-1) of Si both promoted Cd transportation,
but the medium application (Si 30 mg.kg-1) restrained Cd transportation. With
increasing silicon fertilizer application, Cd contents in brown rice increased
first and then decreased, ranging from 0.07-0.15 mg.kg-1, remaining lower than
0.2 mg.kg-1. In the severely Cd-contaminated soil, Si restrained the soil Cd
transportation from the rice root to the shoot. The Cd contents in brown rice,
husk, and straw were reduced by 38.7%-48.5%, 35.7%-70.7%, and 30.9%-40.7%,
respectively, and Cd contents in brown rice were 0.23-0.28 mg.kg-1. Considering
rice grain yields and Cd contents in brown rice, it was recommended that the Si
application be 30 mg.kg-1 of Si in the slightly Cd-contaminated soil and Si 15-60
mg.kg-1 in the severely Cd-contaminated soil.
PMID- 29964595
TI - [Uptake and Volatilization of Gaseous Elemental Mercury by Paddy Rice].
AB - Wetlands are important sinks for mercury, and its reducing substrate favors the
production of gaseous elemental mercury. In order to adapt to the anoxic
condition, wetland plants usually have developed aerenchyma to transfer oxygen
from the shoots to the roots to supply their roots respiration. In this study, a
typical wetland plant, rice, is used to investigate whether its aerenchyma can
also be a channel for the transportation of rhizosphere gaseous mercury into the
atmosphere. In addition, the underlying mechanisms will be evaluated. In this
study, the roots of rice were separated from the shoots by an air-tight chamber.
Roots were exposed to saturated mercury vapor in the root chamber, and the
gaseous mercury volatilized from the leaf chamber was absorbed by an active
carbon absorbent. The results showed that gaseous elemental mercury could be
transferred to shoots after absorption by the roots. The mercury in the roots
decreased polynomially with root porosity (R=0.8309, P<0.01), while the mercury
in the above ground tissues showed a positive correlation with root surface area
and root volume (R=0.896, P<0.01; R=0.871, P<0.01). It was also indicated that
the mercury absorbed by the roots could be volatilized into the atmosphere
through the leaves. The volatilization of the mercury from the leaves increased
positively with the leaf area (R=0.897, P<0.01). There was also a significant
positive correlation between the mercury volatilization per unit leaf area and
transpiration intensity (R=0.73,P<0.01). The results proved that rice can absorb
gaseous elemental mercury through its roots and transfer it above ground for
emission into the atmosphere through the stomata of the leaves. This provides a
scientific basis for further investigations to reveal mercury behavior and its
mechanisms in wetland ecosystems.
PMID- 29964597
TI - [Control Effect of Side Deep Fertilization with Slow-release Fertilizer on
Ammonia Volatilization from Paddy Fields].
AB - In order to reduce the ammonia volatilization in paddy fields, seven treatments
were evaluated. These included three slow-release nitrogen fertilizers[sulfur
coated urea (SCU); resin-coated urea (RCU); release bulk blending fertilizer
(RBB)], two fertilization modes[single base fertilization (B) and combined with
panicle fertilizer (BF)], and conventional split fertilization (CN). The effects
of side deep fertilization for slow-release nitrogen fertilizers on ammonia
volatilization and surface water nitrogen dynamics were examined using a rice
transplanter with a fertilizer sowing mechanism in the Taihu Lake region. The
results showed that total nitrogen and ammonium nitrogen concentration in the
surface water of the SCU treatment in the base period were higher, and those for
RCU and RBB were lower than in the CN treatment. The cumulative ammonia
volatilization during the whole rice season varied among different types of slow
release nitrogen fertilizers from 3.84% to 28.17% of the total N applied. The
nitrogen loss from ammonia volatilization using the three slow-release nitrogen
fertilizers was decreased when compared with conventional split fertilization.
The ammonia volatilization loss exhibited the following relationship for the
treatments:CN, B-SCU > BF-SCU, BF-RBB, BF-RCU, B-RBB, and B-RCU. When the slow
release nitrogen fertilizers were applied in single base fertilization, the total
ammonia volatilization for the SCU was significantly higher than those for the
RCU and RBB, while no significant differences were detected when these three slow
release fertilizers were combined with panicle fertilizer. Moreover, although the
ammonia volatilization of BF-SCU was lower than that of B-SCU, those of BF-RCU
and BF-RBB were higher than those with the B-RCU and B-RBB treatments,
respectively. There are no significant differences for nitrogen volatilization
when any of these three different fertilizers are applied as B or BF. The results
for the emissions during ammonia volatilization during different stages indicated
that the ammonia volatilization of SCU at the basal-tillering fertilization stage
(7.54%) and the tillering-panicle fertilization stage (16.04%) were higher than
those of the panicle fertilization-mature stage. The N loss from ammonia
volatilization for RBB in the base-tillering fertilization stage (2.91%)
increased more than in the tillering-panicle fertilization stage and panicle
fertilization-mature stage. For RCU treatment, the highest rate for ammonia
volatilization was detected at the panicle fertilization-mature stage (2.75%).
Compared with the single base fertilization mode, ammonia volatilization during
the panicle fertilization-mature stage was increased when combined with panicle
fertilizer (BF) for the slow-release fertilizer. There was no obvious correlation
between the N loss with ammonia volatilization for the three slow-release
nitrogen fertilizers and the concentration of ammonium nitrogen in surface water
during the panicle fertilization-mature stage.
PMID- 29964596
TI - [Long Term Variations of Ozone Concentration of in a Winter Wheat Field and Its
Loss Estimate Based on Dry Matter and Yield].
AB - Surface ozone pollution and its negative effects on crops and food safety have
attracted the attention of many people. In this study, ozone concentration and
meteorological parameters in a winter wheat field were measured from 2014 to
2016. We analyzed the variations in ozone concentration and AOT40 during the
growing season for winter wheat. According to the revised stomatal model, the
leaf stomatal conductance of winter wheat was simulated and verified by comparing
with measured results. Based on the flux model, the leaf stomatal fluxes of
winter wheat were calculated. In addition, we estimated the effects of ozone
concentration on winter wheat dry matter and yield by using exposure-response
relationships and flux-response relationships. The results suggested that the
concentration of ozone gradually increased during the growing season for winter
wheat and showed a distinct unimodal pattern of diurnal variation. The mean
concentrations of ozone were 36.2, 37.7, and 33.6 nL.L-1, respectively, and the
ozone AOT40 values were 17.08, 17.90, and 11.84 MUL.(L.h)-1, respectively, during
the growing seasons for winter wheat from 2014 to 2016. The Jarvis-type factorial
model of stomatal conductance could be used to simulate the stomatal conductance
of winter wheat in the region, and approximately 81% of the variation of measured
stomatal conductance could be accounted for by the model. The leaf stomatal ozone
fluxes of winter wheat were 9.36, 9.32, and 8.65 mmol.m-2, respectively, from
2014 to 2016. Winter wheat yield decreased about 18.03%, and its dry matter
decreased about 19.31% under ozone stress during these three years.
PMID- 29964598
TI - [Effects of Biochar and Organic Fertilizer on Saline-alkali Soil N2 O Emission in
the North China Plain].
AB - Based on the winter wheat-summer maize rotation field experiment, the effects of
biochar and organic fertilizer on saline-alkali soil N2O emissions in the summer
maize season were studied in Binzhou in the Shandong Province to provide a
theoretical basis for reducing N2O emissions from saline-alkali soil. The
experiment includes six treatments with three replications:CK[N:0.2 t.(hm2.a)-1,
P2O5:0.12 t.(hm2.a)-1, K2O:0.2 t.(hm2.a)-1], C1[5 t.(hm2.a)-1biochar], C2[10
t.(hm2.a)-1 biochar], C3[20 t.(hm2.a)-1 biochar], M1[7.5 t.(hm2.a)-1 organic
fertilizer], and M2[10 t.(hm2.a)-1 organic fertilizer]. The same nitrogen,
phosphorus, and potassium fertilizer was applied for each treatment. The results
showed that the dynamic trend of the soil N2O fluxes among different treatments
were similar. The peak N2O emissions occurred after fertilization (base
fertilizer and topdressing). The N2O cumulative emission fluxes accounted for
nearly half of the emissions during the whole growth period, and the N2O
emissions of the C1, C2, and C3 treatments were lower than that of CK after
fertilization. Compared with CK, the N2O cumulative emissions from C1 and C2 were
reduced by 45.3% and 31.6%, respectively, but C3, M1, and M2 increased by 17.3%,
37.4%, and 27.6%, respectively. Biochar and organic fertilizer both affected N2O
emission fluxes. Applying biochar can reduce N2O emissions, while organic
fertilizer can increase N2O emissions. In summary, biochar has a great advantage
in reducing N2O emissions in the farmland.
PMID- 29964599
TI - [Flux Characteristics of CO2, CH4, and N2 O and their Influencing Factors in
Different Types of Ditches on the Chengdu Plain].
AB - In order to study the flux characteristics of CH4, CO2 and N2O in different
ditches and their influencing factors, three types of ditches (an agricultural
ditch, agricultural-living compound ditch, and living ditch) were monitored once
a month from March 2014 to February 2015 using static floating chambers in the
Chengdu Plain. The results showed that:1 Affected by human activities, CO2, CH4,
and N2O fluxes were high in ditches and ranged from -2.26-1504.40 mg.(m2.h)-1,
0.69-40.00 mg.(m2.h)-1, and -2.27-70.35 MUg.(m2.h)-1,respectively. All are higher
in summer compared to autumn and spring, and are lowest in winter. 2 The flux of
CO2 in agricultural-living compound ditches was significantly higher than that in
agricultural ditches and living ditches (P<0.05), and the fluxes of CH4 and N2O
in living ditches were significantly higher than those in agricultural ditches
and agricultural-living compound ditches (P<0.05). 3 Water temperature and
rainfall were the main environmental factors affecting CO2, CH4, and N2O fluxes,
and DO (dissolved oxygen) and TN (total nitrogen) were the main environmental
factors affecting CO2 and N2O fluxes. NH4+-N (ammonium nitrogen) and DO were the
main water quality parameters affecting the CH4 flux.
PMID- 29964600
TI - [Review of CO2 and CH4 Emissions from Rivers].
AB - Streams and rivers play a major biogeochemical role in the global carbon cycle
and act as hot spots for carbon dioxide (CO2) and methane (CH4) emissions to the
atmosphere, excepting their roles of transporting the water and carbon from the
terrestrial environment to the ocean. While carbon gases have been of great
global concern, systematic reviews are still scarce. Given recent recognition of
the pervasiveness of CO2 and CH4 in streams and rivers, this study synthesized
existing research and discoveries to identify patterns and controls for riverine
CO2 and CH4, knowledge gaps, and research opportunities. This study presented a
conceptual framework for sources and the fates of CO2/CH4 from streams and rivers
and used this framework to understand the dynamic processes of fluvial carbon
evasion and potential anthropogenic disturbances. Multiple environmental
influences combined with different contributions of endogenous metabolism and
terrigenous input, and the CO2 and CH4 in streams and rivers showed significant
spatial and temporal variability on a global scale, regional scale, and watershed
scale, which indicates a substantial challenge for understanding the larger-scale
dynamics. For a clearer recognition of how the changing environment and human
activities may modify fluvial CO2 and CH4 dynamics, this study constructed a
system framework of controls on CO2 and CH4 production and persistence in streams
and rivers. The framework of controls can be viewed in terms of endogenous
environmental controls that influence river metabolism (organic matter,
temperature, nutrients, pH, and alternative electron acceptors) and external
factors, including geomorphic and hydrologic drivers and human activities
(agriculture, damming, and urbanization). We point out that the carbon emissions
from rivers should be integrated into the terrestrial carbon budget, and in the
future, more attention should be given to research on the sources of CO2 and CH4
in rivers, the generation and diffusion of CO2 and CH4 at different interfaces,
the spatiotemporal variability of riverine carbon emissions, and the response of
riverine CO2 and CH4 dynamics to the changing environment and human activities.
PMID- 29964601
TI - [Marine Aerosol Using On-board Aerosol Mass Spectrometry].
AB - Marine aerosols were measured in real-time by an on-board signal particle aerosol
mass spectrometer(SPAMS) over the Southeast China Sea. The chemical compositions
and size distribution characteristics of aerosol particles were obtained, and the
sources and ion spectra were analyzed. The results showed that particle number
concentration decreased with the distance apart from the coastal area. In the
coastal area, the aerosol compositions were mainly determined by the emissions of
industry, such as vessel, traffic and coal combustion etc. When it was far from
the continent, aerosols were mainly affected by the sea sources. Aerosol
particles during the observation period disturbed singly with a peak diameter
value of 0.5 MUm. Most of the particles were in the size range of 0.2 MUm to 0.8
MUm. High signal intensity of EC with high K+ intensity in the positive spectrum
and HSO4- intensity in negative spectrum was present in the marine aerosol over
the coastal area. However, the signals of NO3- and NO2- were absent in the
negative spectrum. The signal intensity of EC was weak in the marine aerosol over
the sea area far from the coastal area. High signal intensity of Na+ and weak
Mg+,Ca+ and NaCl+ signals were present in the positive spectrum, while high
signal intensity of MSA-,CN-,O- and HSO4- were present in negative spectrum which
was considered to be the special ions spectrum of marine biological sources. It
indicated that ambient aerosols over the observation area were influenced not
only by the anthropogenic emission sources but also affected by the marine
aerosol formation.
PMID- 29964602
TI - [Analysis of Spatio-temporal Distribution and Variation Characteristics of
Aerosol Optical Depth over the Northwest of China by MODIS C6 Product].
AB - This work compared the collection 6 MODIS aerosol optical depth products with sun
photometer data from AERONET, and evaluated the applicability of C6 merged data
in the northwest of China. The spatio-temporal variation characteristics and
influencing factors of AOD over northwest of China were analyzed by MODIS/AQUA C6
MYD08-M3 products from 2006 to 2015, and the results showed that Southern
Xinjiang and Guanzhong region of Shanxi province had relatively high AOD, whereas
the south of Qinghai and Gansu province had low values; Junggar Basin was the
incremental area of AOD for the first 5 years and second 5 years, whereas
converse result existed in Qaidam Basin and Hetao area. Temporally, the yearly
mean AOD ranged from 0.18 to 0.22, and the declined trend occurred in 2011, and
the annual decrease rate was about 0.32%; Because of different intensity and
frequency of dust weather, the south of Xinjiang showed a significant interannual
variation characteristic; East of the northwest displayed an obviously declining
trend from 2011 to 2015, and the yearly mean decrease was about 1.1%. The AOD in
north of Xinjiang and Qinghai-Tibet remained stable. The seasonal changes of AOD
among different areas over the northwest had the same trend, all gradually
declined from spring to autumn, and increased in winter.
PMID- 29964603
TI - [Sources and Characteristics of Regional Background PM1 in North China During the
Autumn and Winter Polluted Period].
AB - The campaign of investigating the chemical compositions and particle size
distributions of NR-PM1(non-refractory PM1) was conducted by using a High
Resolution Time of Flight Aerosol Mass Spectrometer(HR-ToF-AMS) at the
Shangdianzi(SDZ) regional atmospheric background site(117.07 degrees E, 40.39
degrees N), northeast of Beijing, from October 17th 2015 to January 27th 2016.
The results showed that organics was the main component of PM1, and the
proportion of nitrate was higher than that of sulfate in autumn and winter. The
mean mass-resolved size distributions for the main components displayed
accumulation mode. The wider organic peak shape and larger nitrate peak size
indicated that the organics contributed to both small and large particles at the
beginning of the particle formation, growth and aging processes, while most of
nitrate particles preferred to grow into large particles during the aging
process. The ratios of elements between OM and OC, O/C and H/C were calculated as
1.91, 0.58 and 1.58 respectively. The slope of Van Krevelen diagram of organic
aerosols during polluted episode was -0.21, whose oxidation state was higher than
those of other city sites. Nitrate was the major contributor of NR-PM1 during the
polluted period, while organics was significantly higher than that during clean
period. The results of back trajectories analysis demonstrated that the air
masses were complex during the pollution episode. The northwest wind from central
Inner Mongolia and Siberia dominated the clean episodes, which was conducive to
the spread of pollutants.
PMID- 29964604
TI - [Pollution Characteristics and Light Extinction Contribution of Water-soluble
Ions of PM2.5 in Hangzhou].
AB - The pollution characteristics and light extinction contribution of water-soluble
ions of PM2.5 in Hangzhou were investigated by sampling and laboratory analysis
of aerosol samplers in 2013. The water-soluble ions were dominant in PM2.5 and
the total mass concentration was 37.5 MUg.m-3, accounting for 44.4% of the PM2.5
mass concentration. Water-soluble ions were mainly composed of secondary
ions(SO42-,NO3- and NH4+), which accounted for 83.4% of total ions. The highest
mass concentrations of PM2.5 and major ions were observed in winter and the
lowest in summer. The proportions of water-soluble ions in PM2.5 in summer and
autumn were obviously higher than those in winter and spring and proportions of
secondary ions in water-soluble ions were very close in each season. The
contribution was the greatest to PM2.5 from secondary ions generation caused by
fuel combustion and automobile exhaust. The annual average values of SOR and NOR
were 0.27 and 0.15 respectively, the conversion rate of SO2 in atmosphere was
greater than that of NOx. There was obvious positive correlation between SOR or
NOR and humidity which indicated the important contribution of heterogeneous
oxidation process to the generation of SO42- and NO3-. The annual average of[NO3
]/[SO42-] was 0.63, and the aerosol pollution was primarily affected by emissions
from coal burning. In haze days, with the increase of haze pollution level, the
mass concentrations of PM2.5, water-soluble ions, secondary ions as well as SOR
and NOR all increased gradually, and the stable weather condition in haze days
could efficiently promote the accumulation and secondary conversion of
pollutants. There were obvious positive correlations between mass concentrations
of PM2.5 and SNA and the atmospheric light extinction coefficient. The IMPROVE
formula which was used to calculate the light extinction coefficients of
different chemical components could efficiently indicate the tendency of aerosol
scattering. The extinction contribution of SNA could reach 60.8%. The extinction
coefficient of SNA was the highest in winter and lowest in summer, and its value
and contribution proportion both increased gradually as the haze pollution level
rose.
PMID- 29964605
TI - [Formation and Size Distribution of the Secondary Aerosol Inorganic Ions in
Different Intensity of Haze in Qingdao, China].
AB - Size-segregated atmospheric aerosol samples were collected from September 2015 to
February 2016 at a coastal site in Qingdao, and the concentrations of major water
soluble inorganic ions were analyzed by ion chromatography. Characteristics and
variation of size distribution of secondary inorganic components in aerosol were
discussed, as well as the formation process and influencing factors of
SNA(sulfate, nitrate and ammonium). The results indicated that the concentrations
of NO3-, SO42-, NH4+, NO2-, Cl- in the aerosols were in the range of 10.32
193.46, 4.42-74.05, 2.21-57.75, 0.05-2.22 and 1.35-17.39 MUg.m-3 respectively.
And the mass concentration of SNA increased with the intensity of haze pollution.
The concentrations of NO3- on the slight, mild, moderate and severe haze days
were 55%, 77%, 240% and 537% higher than that on non-haze days respectively,
while concentrations of SO42- increased by 4.7%, 35%, 77% and 262% respectively,
and concentrations of NH4+ increased by 72%, 83%, 201% and 526% respectively. The
contribution of these water-soluble ions to PM2.5 showed that the proportion of
sum of NO3-, SO42-, NH4+, NO2- and Cl- to PM2.5 was in range of 62.03%-80.93%.
The proportion of ion to PM2.5 decreased in the order of NO3- > SO42- > NH4+ > Cl
> NO2-. With the enhancement of haze pollution, the proportion of NO3- in PM2.5
increased from 29.53% to 45.54%. The correlation analysis showed that NO3- and
SO42- in the fine particle were significantly correlated with gaseous precursors
NO2 and SO2, and also showed good correlations with relative humidity,
visibility, wind speed and other weather conditions. These results indicated that
the formation of SNA in fine particles was one of the main reasons for visibility
decrease and the formation of air pollution in haze days. Meanwhile, high
concentration of gaseous precursors, high relative humidity and low wind speed
were the important influencing factors of haze formation. Except for slight haze
days, SOR and NOR in the haze days were higher than those on the non-haze days,
and increased significantly with the intensifying of haze, especially for 0.43
0.65 and 0.65-1.1 MUm particle size. Conversion rates of nitrogen and sulfur in
severe haze days were 1.5 times that in non-haze days, which showed nitrate and
sulfate in these fine mode were mainly from gas-to-particle conversion. NO3-,
SO42-, NH4+ and NO2- increased in haze significantly, which mainly existed in the
fine particles. The cloud process played a more important role on haze days.
While on non-haze day, cloud process and the heterogeneous reaction were both the
main factors. And the highest proportion of fine mode concentration to total one
was observed for NO3-(79.4%) and SO42-(74.4%) on severe haze days respectively.
NO3- showed a bimodal distribution with peaks in the size-bin of 0.43~0.65 MUm
and 3.3-4.7 MUm on non-haze, slight, mild haze days, and the fine peak moved to
0.65-1.1 MUm on moderate haze days, however the bimodal distribution changed to
unimodal distribution with peak at 0.65-1.1 MUm on severe hazy days. SO42- showed
a bimodal distribution with peaks at 0.43-0.65 MUm and 2.1-3.3 MUm in the non
haze weather, while the size distribution changed to unimodal distribution on
hazy days. But the peak sizes were different in different intensity of haze, with
peak at 0.43-0.65 MUm on mild and slight haze and 0.65-1.1 MUm in moderate and
severe haze days. NH4+ showed a single peak distribution in the fine mode, with
the peak in the particle size of 0.43-0.65 MUm on slight and non-hazy days, and
0.65-1.1 MUm on mild, moderate and severe hazy days. Therefore, haze has a great
influence on the size distribution of SNA.
PMID- 29964606
TI - [Comparison of Characteristics and Reactive Oxidative Species of PM2.5 in Xi'an,
China During Haze and Clean Days].
AB - PM2.5 samples were collected in Xi'an, China during haze(2015-11-30-2015-12-9)
and clean days(2016-01-13-2016-01-22). PM2.5 mass, organic carbon(OC), elemental
carbon(EC), and water-soluble ions(i.e., NH4+, NO3-, and SO42-) were measured to
investigate the characteristics of the two typical pollution processes. The
result showed that PM2.5 masses were(170+/-47.5) MUg.m-3 and(48.6+/-17.9) MUg.m-3
for the haze and clean days, respectively, with the haze accompanied by low
visibility, high humidity, calm wind, and other adverse weather conditions. The
secondary inorganic aerosol(SIA) including NH4+, NO3-, and SO42- accounted for
49.8%+/-13.1% and 19.4%+/-5.95% of the PM2.5 mass for the haze and clean days,
respectively. sulfur and nitrogen oxidation ratios(SOR and NOR) on haze days were
0.282+/-0.157 and 0.269+/-0.124, respectively, which were much higher than those
measured on the clean days(0.189+/-0.057 and 0.077+/-0.046). The average
concentration of secondary organic carbon(SOC) for the haze days(6.22+/-3.87)
MUg.m-3 was 5 times of that measured in the clean days(1.44+/-1.63) MUg.m-3.
Secondary pollution and adverse weather conditions were the main reasons for the
heavy haze. Finally, the level of particulate-Reactive Oxygen Species(ROS)was
measured by the 2',7'-dichlorofluorescin diacetate(2',7'-DCFH) fluorescence
method, and the average ROS concentration (as H2O2) was(4.99+/-1.54) nmol.m-3
during haze days and(0.492+/-0.356) nmol.m-3 during clean days. Accumulation
effect and secondary oxidation process may be the main reasons for the increase
of ROS concentration under the heavy haze conditions in Xi'an. Positive
correlations(P<0.05) between the concentrations of ROS and the ions of NO3- and
SO42- indicated that ROS may participate in secondary oxidation process of SIA.
PMID- 29964607
TI - [Seasonal Variation and Sources of Dicarboxylic Acids and Related Compounds in
PM10 from Mt. Huangshan].
AB - To identify the seasonal variation of dicarboxylic acids and related compounds in
PM10 from Mt. Huangshan. PM10samples were collected during the summer and winter
of 2015, which were then analyzed for dicarboxylic acids, ketocarboxylic acids,
and alpha-dicarbonyls. The results showed that oxalic acid(HOOC-COOH, C2) was the
dominant species in the summer and winter months, followed by malonic acid(HOOC
CH2-COOH, C3), and succinic acid[HOOC-(CH2)2-COOH, C4], being consistent with
that in other high-altitude regions. Most of the diacids were more abundant in
the summer months than in the winter months, while adipic acid(C6) and phahalic
acid(Ph) were twice lower in the summer months, suggesting significant impact of
anthropogenic pollution on the wintertime alpine atmosphere. Moreover, as major
precursors of C2, glyoxal(Gly) and methylglyoxal(mGly) were also lower in the
summer months than in the winter months, which were opposite to those of the
diacids, indicating that the mountain troposphere was more oxidative in the
summer months than in the winter months. Principal component analysis(PCA)
further revealed that the wintertime SOA in the Mt. Huangshan troposphere mostly
originated from the anthropogenic pollutants from long-distance transport.
Conversely, the summertime SOA mostly originated from the further oxidation of
the mountainous biogenic sources. The AIM(Aerosol Inorganic Model) calculation
results showed that the aqueous-phase C2 production was the primary mechanism of
C2 formation in ambient aerosol and was driven by acid-catalyzed oxidation in
summer.
PMID- 29964608
TI - [Composition Characteristics and Sources Apportionment of Lanthanoid in PM2.5 of
Quanzhou].
AB - Samples of PM2.5 were collected from 5 sites in Quanzhou in March, April and
July, 2014. The concentrations of lanthanoid and other trace metals in the PM2.5
were determined by Inductively Coupled Plasma Mass Spectrometry(ICP-MS). The
total lanthanoid concentration (SigmaLoid), the ratio of light-lanthanoid(L Loid,
including, La, Ce, Pr, Nd, Sm and Eu) to heavy-lanthanoid(H Loid, including Gd,
Tb, Dy, Ho, Er, Tm, Yb and Lu) in PM2.5 were 2.490-5.708 ng.m-3(65.682-126.529
MUg.g-1) and 12.086-14.319, respectively. The distribution pattern of Loid in
PM2.5 was also evaluated in this study. All PM2.5 samples showed similar
distribution pattern with local topsoil. And positive Ce and negative Eu
anomalies were observed in PM2.5. La-Ce-V plots and chemical mass balance(CMB)
model were used for source identification and apportionment of PM2.5in Quanzhou.
The CMB model was used to identify four main sources:urban fugitive dust, coal
combustion, vehicle exhaust and waste incineration emission which had a
contribution of 18.9%, 10.9%, 30.6% and 30.2%, respectively.
PMID- 29964609
TI - [Pollution Characteristics and Health Risk Assessment of Hazardous Air Pollutants
in the Surroundings of Three Petrochemical Industries in Northwest China].
AB - The samples in the surroundings of three representative petrochemical industries
in Northwest China were collected by summa canister/adsorption using activated
carbon/glass fiber filter, and then they were analyzed for 13 hazardous air
pollutants by gas chromatography-mass spectrometry/gas chromatograph/high
performance liquid chromatography. The pollution characteristics and human health
risk of hazardous air pollutants were discussed. The results showed that 8
hazardous air pollutants existed in the surroundings of all petrochemical
industries. The detection frequency for 8 hazardous air pollutants exceeded 80%.
The ranges of the average concentrations of benzene series(BTEX), 1,3-butadiene,
1,4-dichlorobenzene, benzo[a]pyrene were 48.01-182.75 MUg.m-3, 6.28-7.95 MUg.m-3,
5.53-12.62 MUg.m-3 and 7.03-36.08 ng.m-3. Daily average concentration of
benzo[a]pyrene was 1.8-13.4 times higher than the limit of national standard
level-II, and those of benzene, toluene and xylene were also over their limits of
standard to different degrees. The non-carcinogenic risks of benzo[a]pyrene and
1,3-butadiene were beyond acceptable levels around the three petrochemical
industries in Northwest China. Meanwhile, the non-carcinogenic health impact of
benzene was appreciable on the exposed population of Lanzhou petrochemical
industrial area. The carcinogenic risks of benzene, ethylbenzene, styrene, 1,3
butadiene, 1,4-dichlorobenzene and benzo[a]pyrene were beyond acceptable levels.
At the same time, the carcinogenic risks of benzene, 1,3-butadiene and 1,4
dichlorobenzene were significantly higher than their acceptable ranges
recommended by US EPA.
PMID- 29964610
TI - [VOCs Characteristics and Sources Apportionment in Yixing City During the G20
Summit].
AB - A continuous measurement was conducted in Yixing city urban area from 24th August
to 15th September using TH-300B continuous online GC-MS instrument during G20
summit in Hangzhou, 2016. The VOCs average mass concentrations of alkane, alkene,
aromatic, acetylene, haloalkane hydrocarbons, OVOC and acetonitrile were 11.00*10
9, 1.93*10-9, 5.78*10-9, 1.23*10-9, 4.16*10-9, 10.37*10-9, 0.27*10-9,
respectively. The photochemical reaction activity was calculated by using the
maximum potential coefficient of Ozone Formation Potential. Alkene and aromatic
hydrocarbons were the most active components of OFP. By applying the positive
matrix factorization(PMF)model, five major factors were extracted to identify the
sources of NMHCs in Yixing city, including industry(42.2%),vehicle
exhaust(17.9%), fuel evaporation(20.8%), paint/solvent usage(7.0%)and
plant(12.1%). Combined with the conditional probability function(CPF) analysis,
source of anthropogenic pollution was related to the distribution of industrial
enterprises in the northwest and southeast, while the plant source was related to
the forest hilly region of Southwest Yixing city. The effect of air pollutant
emission reduction showed that the primary emission air pollutants had declined
significantly during the strict control period from 1th to 6th September in G20
summit,2016, and the industry proportion was reduced to 30.5%, whereas the plant
proportion increased to 16.8%.
PMID- 29964611
TI - [Agricultural Ammonia Emission Inventory and Its Spatial Distribution in Sichuan
Province from 2005 to 2014].
AB - Based on the urban activity data and emission factors, agricultural ammonia
emission inventory was developed for Sichuan province from year 2005 to 2014.
Meanwhile, its historical trends, spatial distribution and the relationship
between agricultural ammonia emission and PM10 concentration were analyzed. The
results showed that the highest emission was estimated to be 111.9*104 t in 2006,
which was reduced to 95.5*104 t in 2014. The interannual variation
characteristics were different for 21 cities in Sichuan, the annual emission of
Chengdu, Meishan, Zigong, Luzhou, Yibin, Panzhihua, Aba and Ganzi changed largely
in the study period. Livestock source and nitrogen fertilizers were the major
contributors, accounting for 72%-79% and 20%-27% of the total agricultural NH3
emission respectively. Hog, poultry and cow were the major contributors under the
category of livestock sources for the most cities. It's worth mentioning that
rabbit was the largest contributor in Zigong, accounting for 39% of the total
livestock NH3 emission. The urban and sub-urban areas of Chengdu, the
northeastern and southern part of Sichuan were the hot-spots for agricultural NH3
emission. In term of spatial distribution, there were higher emissions in the
east of Sichuan and other suburban and rural areas. There was a good agreement
between agricultural NH3 emission and PM10 concentration, indicating agricultural
NH3 emission played an important role in the particle formation.
PMID- 29964613
TI - [Estimation of Health Risk and Enaction of Safety Standards of N
nitrosodimethylamine(NDMA) in Drinking Waters in China].
AB - Nitrosamines such as nitrosodimethylamine(NDMA) in drinking water have recently
attracted great attention because of their high carcinogenicity and high
detection rate. Nitrosamines have also been repeatedly detected in drinking water
in our country, leading to a lot of concerns about our drinking water safety.
However, China has not yet formulated the relevant drinking water safety
standards. In order to evaluate the health risks caused by NDMA in drinking water
and to provide recommendations for the development of drinking water safety
standards, the method of disability-adjusted life years(DALYs) and the two-stage
disease model were used to estimate the health risk of liver cancer caused by
intake of NDMA in drinking water. The data of this study were collected from two
large-scale water quality surveys conducted in 35 cities in China from November
2009 to May 2012, and the detection conducted by Chen Chao et al. in 23 cities in
China from 2012 to 2014, with a total of 146 water plants data. The results
showed that mean(8.97 ng.L-1) and median(2.90 ng.L-1) NDMA concentrations were
both not very high except in some special areas. The incidence of life-long
cancer was 5.69*10-6 and 5.69 times as high as the negligible risk value(1*10-6)
specified by the US EPA. The total disease burden of NDMA was 844.15 person
years, of which the death loss was 818.31 person-years, accounting for 96.9%. The
incapacity loss was 25.84 person-years, accounting for 3.1% in comparison. Death
loss was greater than the loss of incapacity. The disease burden was highest in
the age group of 55-60 years(129.40 person-years), followed by 45-50 years(120.44
person-years). The burden of disease was higher in middle-aged and elderly
people. The averaged loss was 6.27*10-7 DALYs per person per year in our country.
Only considering the health risk factors, NDMA concentration safety standards
should be 6.12 ng.L-1. According to the specific national conditions, the NDMA
safety standard in the range of 6-40 ng.L-1 was recommended. On one hand, we can
control the concentration of NDMA in drinking water, to reduce health risks as
far as possible, and on the other hand, we can also ensure the effectiveness of
disinfection of drinking water treatments. China's economic and water treatment
technological level and other factors should also be taken into consideration in
the near future. In view of potential health risks of NDMA, it's necessary to
adopt more effective, economical and also environmental water treatment
techniques and develop reasonable safety standards to ensure the quality of
drinking water and people's health.
PMID- 29964612
TI - [Air Pollutant Emission Inventory of Non-road Machineries in Typical Cities in
Eastern China].
AB - Based on site investigation of non-road vehicles in Shanghai and Hangzhou located
in east China, non-road vehicle emission inventory in 2014 was established in
these cities as well as its emission inventory technology. Characteristics of non
road vehicle were also analyzed, including classification, type of fuel, power
and emission standard. The results showed that diesel consumed by non-road
vehicles was 6.1*105 t in Shanghai and 3.2*105 t in Hangzhou; NOx emission was
3.09*104 t in Shanghai and 1.72*104 t in Hangzhou; PM2.5 emission was 1.41*103 t
in Shanghai and 8.1*102 t in Hangzhou, 2014. Emissions from excavators and other
construction equipment contributed the most in non-road vehicle emission
inventory. Non-road vehicle has become one of the important sources of urban air
pollution, whose NOx emissions accounted for 11.1% of all urban sources in
Shanghai and 16.1% in Hangzhou, and accounted for 18.5% of mobile sources in
Shanghai and 32.2% in Hangzhou.
PMID- 29964614
TI - [Comparison and Analysis of the Quantitative Methods for Pollutant Sources Load
in Groundwater Contamination Risk Assessment].
AB - Groundwater contamination risk assessment is an important basis for the
protection of groundwater resources and the prevention and control of groundwater
pollution. Its evaluation system is usually composed of three elements, which is
vulnerability, pollutant source load and groundwater value. The pollutant source
load plays an important role in risk assessment. Because of the difference among
methods for pollutant sources load quantification, there will inevitably be
different demand for the basic information survey on pollutant sources, as well
as unknown impact on the final assessment results. In order to explore the impact
of quantitative methods for pollutant sources load on groundwater contamination
risk assessment, a case study was conducted in the mesoscale region of alluvial
fan in Hutuo River, China. The two representative methods of grading index and
quantitative index assessment systems were applied to quantify the pollutant
sources load, in combination with the same vulnerability and groundwater value.
The results constructed from different risk assessment systems were compared. The
results showed that there were great differences between the two methods of
quantification for pollutant sources load, and the result of contamination risk
assessment also revealed significant differences in the feature of risk valve and
the spatial distribution of the risk levels. The results of contamination risk
assessment were strongly influenced by the choice of quantification for pollutant
sources load methods. The grading index method was suitable for large scale
region with lower precision of basic information and was simple, and the results
of assessment had relatively lower reliability. The quantitative index method was
suitable for the mesoscale and micro-scale region with higher precision of basic
information and was relatively complicated, and the results of assessment had
relatively higher reliability. It was shown that the scale effect of evaluation
region had an important influence on the choice of methods.
PMID- 29964615
TI - [Distribution and Sources of n-alkanes in Surface Seawater of Jiaozhou Bay].
AB - Hydrocarbons emitted by human activities probably constitute the largest class of
contaminants that are present in coastal areas, because of widespread use of
fossil fuels for power generation and logistics, and accidental spillages. The
chemical composition of hydrocarbon mixtures found in the marine environment
allowed the identification of relative contributions of different natural and
anthropogenic sources. Identification of these hydrocarbons, especially n
alkanes, could act as tracers for the possible sources. To evaluate n-alkanes
concentrations with emphasis on source analysis, surface water without visible
oil was collected from the cruise in April 2016. Determination and quantification
were performed by solvent extraction and gas chromatography-mass spectrometry.
Various molecular diagnostic parameters were used to assess the contribution of
different sources and origin of n-alkanes in surface seawater of Jiaozhou Bay.
Concentrations of total dissolved n-alkanes(C11-C37) were between 1.756-39.09
MUg.L-1 with a high carbon number predominance profile without odd-even carbon
number preference. The n-alkane concentrations varied spatially depending on the
distance away from main input sources and the ability of water exchange. It was
at a higher concentration in the northeast and west coastal areas, as well as the
mouth of Jiaozhou Bay. And concentrations were relatively lower in the inner area
and outside of Jiaozhou Bay. In the sea area with strong water exchange,
concentrations of total n-alkanes were around 2.196 MUg.L-1, which could be
considered as the environmental background level of n-alkanes in Jiaozhou Bay.
Those n-alkanes were dominated with C24, with a slightly odd carbon number
preference in low carbon n-alkanes and an even carbon number preference in high
carbon n-alkanes. The values of CPI for the whole range of n-alkanes series, low
carbon n-alkanes, and high carbon n-alkanes were 0.949, 1.026, and 0.980,
respectively. Diagnostic indices and curves indicated that the dominant inputs of
those n-alkanes were from marine biogenic input such as algae and marine
bacteria. The concentration profiles of n-alkanes in other areas were
characterized by no odd-even predominance in the range of C21-C33 with peaks
center at C24 which were indicative of anthropic contributions as emission
sources. N-alkanes dominating with anthropic sources comprised a high
proportion(83.7%) of total n-alkanes. Activities of harbors and ships were the
main contributors of Jiaozhou Bay n-alkanes. Physical processes, such as
evaporation and dilution, were the principal weathering mechanisms. Because of
its sufficient environmental capacity, Jiaozhou Bay was still moderately
contaminated with petroleum.
PMID- 29964616
TI - [Spatial Variations of CO2 Degassing Across Water-air Interface and Its Impact
Factors in Summer in Guijiang River, China].
AB - River is characterized by obvious spatial heterogeneity in catchment, which is
exacerbated by special environment features of calcium-rich, alkaline and DIC
rich(dissolved inorganic carbon) in karst river. Thus, it also leads to
significant spatial variation in the CO2 degassing across water-air interface.
Main ions, physicochemical parameters, delta13CDIC value and two common
approaches(floating chamber(FC) and thin boundary layer models(TBL) were used to
analyze the CO2 degassing characteristics in Guijiang River, a karst river,
China. The results were as follows:1 Hydrochemistry in Guijiang River basin
showed a significant spatial change. All of HCO3-, Ca2+, specific conductivity,
total dissolved solids(TDS), SIc and pCO2 showed similar distribution
characteristics in the following order:tributaries in the middle reaches > middle
reaches > Downstream > Upstream of Guijiang River. 2 During the monitoring
period, CO2 degassing occurred in all the sampling sites and it was the CO2
source for the atmosphere. The mean CO2 evasion was 237 mg.(m2.h)-1 in Guijiang
River, which located in the range of average CO2 evasion of global river.
However, significant spatial variations also occurred along Guijiang River. The
CO2 degassing flux in tributaries of the middle reaches and middle reaches of the
mainstream were obviously larger than those in downstream and upstream of the
mainstream. 3 CO2 degassing was mainly affected by carbonate equilibrium system
in tributaries in the middle reaches and middle reaches in the mainstream of the
Guijiang River basin, which resulted in obviously larger CO2 degassing than those
in downstream and upstream of mainstream. However, the CO2 degassing flux in
tributaries of the middle reaches was also simultaneously affected by biological
photosynthesis, and the minimum CO2 degassing flux[6.38 mg.(m2.h)-1] appeared in
tributaries of the middle reaches. In addition, the CO2 degassing flux in
mainstream upstream was mainly affected by atmospheric environmental factors,
while it was synergetically influenced by many factors in mainstream downstream.
PMID- 29964617
TI - [Spatial Distribution Characteristics and Potential Ecological Risk of Antimony
and Selected Heavy Metals in Sediments of Duliujiang River].
AB - In order to investigate the spatial distribution characteristics of Sb and
selected heavy metals, and to discriminate their sources and potential ecological
risks in surface sediments of the Duliujiang river,a total of 62 surface sediment
samples were collected in this study. Total contents of Sb, As, Cd, Co, Cr, Cu,
Mo, Ni, Pb, Tl, Zn and Fe in these samples were measured by inductively coupled
plasma mass spectrometry(ICP-MS) and the inductive plasma optical emission
spectrometry(ICP-OES). Principal component analysis(PCA) and Pearson correlation
analysis were used to deduce the potential sources of these elements. Geo
accumulation index(Igeo), enrichment factor(EF) and Hakanson's potential
ecological risk index(Eri and RI) were calculated to evaluate the pollution
degree of heavy metals in sediments. The results indicated that the contents of
heavy metals in sediments were impacted by human activities to different extents,
and the Duliujiang River was significantly contaminated by Sb. The contents of Sb
in sediments reached up to 7080 mg.kg-1, and gradually decreased from upstream to
downstream, while the contents of As, Cd, Co, Cr, Cu, Mo, Ni, Pb, Tl and Zn
varied indistinctively. The PCA results showed that the cumulative proportion of
the first two components accounted for 77.67% of the total variables, suggesting
that two major sources of Sb and other heavy metals were mining/smelting industry
and natural sources. The calculated Igeo and EFs also showed that the surface
sediments of the Duliujiang River were majorly polluted by Sb, followed by As and
Co, lightly contaminated with Co, Cu, Mo, Ni, Pb and Tl, and uncontaminated with
Cr. The ecological hazards(Eri) for each metals in a descending order were Sb >
Cd > As > Co > Ni > Pb > Cu > Zn > Cr. The comprehensive index of potential
ecological risks(RI) for heavy metals indicated that 58.1% of the 62 sediments
samples had more than moderate ecological risks, and the sites with high RIs were
generally located around Sb mining area and the downstream of the Baluo River. In
addition, the Eri of Sb was a predominant component of RI, indicating that the
Duliujiang River is an area with extremely high potential ecological risk of Sb.
PMID- 29964618
TI - [Distribution Characteristics and Potential Risk of Bisphenol Analogues in
Surface Water and Sediments of Lake Taihu].
AB - In this study, seven bisphenol analogues were measured in water and sediment
samples from Taihu Lake, and potential risk was evaluated. The results showed
that BPF, BPS and BPA were the predominant components in water samples from Lake
Taihu. In sediment, BPA was always predominant, followed by BPF and BPS, and
there was a significant positive correlation between BPs and TOC content. In
addition, the high concentration levels of BPF, BPS and BPA were distributed in
the tributaries of Lake Taihu(S4-S10). The risk assessment of the target BPs
showed that the combined risk quotients posed a low eco-toxicity to aquatic
ecosystem, and there was no appreciable risk to human health from potential
environmental exposure of drinking water.
PMID- 29964619
TI - [Characteristics of Water Extractable Organic Nitrogen from Erhai Lake Sediment
and Its Differences with Other Sources].
AB - The 47 samples from Erhai Lake surface sediments were collected in different
seasons. The distribution and structure characteristics of sediment water
extractable organic nitrogen(WEON) were investigated by using the combined
techniques of UV-Vis absorption and three-dimensional excitation-emission matrix
spectra(3DEEMs). The differences in DON of various sources(overlying water, pore
water, inflow Rivers and wet deposition) were explored to analyze its effects on
sediment. The results showed that:1the temporal distribution followed the pattern
of summer > spring > autumn > winter, with the spatial WEON distribution of
northern > southern > central. 2 The humic degree of Erhai sediment WEON was
relatively high and mostly composed of fulvic acid, which mainly contained UV
like humic-like fluorescence peak A and high-excited tryptophan fluorescence peak
B. This indicated that it was mainly affected by terrestrial input and microbial
activity. 3 There were two fluorescent components(C1, C2) in the sediments and
other sources of Erhai Lake. The component C1 was the endogenous visible
ultraviolet peak formed by biodegradation, while the component C2 was the
tryptophan peak. The bioavailability of wet deposition samples was comparatively
high, greatly impacting Erhai Lake in heavy rainfall. The DON bioavailability in
the inflow river was the lowest, which was prone to be accumulated in sediments.
4The DON component C1 and C2 in overlying water had significant negative
correlation with Erhai sediment WEON contents(r=-0.79, P<0.01;r=-0.944, P<0.01).
This suggested that the overlying water DON components could indirectly reflect
the sediment WEON content of Erhai Lake, namely the higher the fluorescence
components C1 and C2 in overlying water DON were, the lower the sediment WEON
content was.
PMID- 29964620
TI - [High-resolution Distribution Characteristics of Phosphorous, Iron and Sulfur
Across the Sediment-Water Interface of Aha Reservoir].
AB - In situ two-dimension, high-resolution distribution of phosphorus(P), iron(Fe),
sulfur(S) from the sediment-water interface was investigated in different areas
of Aha Reservoir, a typical sub-deep water lake, using diffusive gradients in
thin films(DGT) technique, combining with water chemistry and sedimentary
phosphorus speciation analysis, aimed to discuss the distribution and control
factors of P-Fe-S in sediments. DGT-P ranged from 0.00 mg.L-1 to 0.43 mg.L-1. DGT
Fe rangd from 0.00 mg.L-1 to 2.83 mg.L-1. DGT-S ranged from 0.00 mg.L-1 to 0.10
mg.L-1. There was no significant correlation among the concentrations of P, Fe, S
in the sediment pore water of Aha Reservoir, which is markedly different from the
results of previous studies. We hypothesize that the high ratios of Fe/P and Fe/S
induced the direct reaction of surplus Fe(III) with S2-, yielding FeS and/or
FeS2, while P was firmly fixed in sediments by Fe(III). NaOH-SRP(ranging between
192 and 604 mg.kg-1) and BD-P(ranging between 143 and 524 mg.kg-1) were the two
major fractions of P in sediments. Since the environment for the bottom layer of
water in Aha Reservoir is anoxic, the geochemical cycle of Fe and S potentially
has a massive impact on the activation and migration of sedimentary P.
PMID- 29964621
TI - [Distribution Characteristics of Drugs of Abuse and Their Metabolites in Aqueous
Environment of Beijing, China].
AB - This work investigated the occurrence and distribution of six drugs of abuse and
their metabolites, i.e. methamphetamine(METH), amphetamine(AMP), ketamine(KET),
ephedrine(EPH), methcathinone(MC) and hydroxylimine(HY) in the surface water and
groundwater in Beijing, China. Forty-three samples were collected and analyzed by
solid-phase extraction and high performance liquid chromatography coupled to
tandem mass spectrometry(SPE-HPLC-MS/MS). The result showed that KET, MC and HY
were not detected in any of the analyzed samples. EPH was the most abundant and
ubiquitous compound in the surface water, with the detection frequency of 42% and
average concentration of 10.1 ng.L-1, followed by METH(25%, average 1.8 ng.L-1).
Only trace amount of AMP was detected in some groundwater samples(n.d.-2.2 ng.L
1), with detection frequency of 21%. Spatial variation of target drug
concentrations in the aqueous environment was also studied, and the highest
levels of METH and EPH were observed in Liangshui River. Risk assessment
suggested that the RQ values of target compounds were lower than 0.10. Although
no toxic effects could be expected at the current levels, further studies are
needed to assess the long-term effect of drugs of abuse and their metabolites on
organisms as well as the joint toxic effect.
PMID- 29964622
TI - [Impacts of Rainfall Characteristics and Occurrence of Pollutant on Effluent
Characteristics of Road Runoff Pollution].
AB - Urban road runoff contains pollutants such as particulate matters, organic
chemicals, heavy metals, nutrients, oil and grease that can cause significant
degradation of receiving water quality. Eliminating the pollutant mass loading of
road runoff and protecting the receiving water bodies have been the focuses in
environmental field in recent years. To accomplish pollutant reduction and
develop a cost-effective treatment method, knowledge of water quality
characteristics, as well as the pollutant effluent characteristics of road runoff
is required. In order to investigate the impacts of rainfall characteristics and
occurrence of pollutant on the variation of pollutant concentrations during the
duration of runoff events and pollutant load effluent characteristics of road
runoff, 207 road runoff samples in the durations of 13 storm events occurred at
Taibai Interchange of the south second-ring road in Xi'an, Shaanxi province from
July 2014 to September 2015 were collected by the manual time-interval sampling
method, and concentrations of SS, COD, dissolved COD, Cu, dissolved Cu, Pb,
dissolved Pb, Cr, dissolved Cr, Cd and dissolved Cd of the samples were
determined. The results indicated that, the road runoff of Xi'an city was
seriously polluted by SS and COD, which were the main contaminants in road
runoff. Meanwhile, concentrations of Pb and Cr in road runoff were also at a high
level. The variation of pollutant concentrations during the duration of runoff
was closely related to rainfall characteristics and occurrence states of the
pollutants. Emission of the dissolved pollutants was not affected by the type of
rainfall. The concentration of the dissolved pollutants in the runoff reached a
peak in the initial duration of runoff, and then, decreased continuously.
However, the peak concentration of particulate pollutants in the runoff only
occurred after the peak of sufficiently large rainfall intensity. The
concentration of particulate pollutants in the runoff fluctuated sharply with the
variation of rainfall intensity, and impacted by the rainfall duration and
rainfall depth as well. Rainfall characteristics didn't have a great impact on
the load emission of the dissolved pollutants, therefore, had a significant
influence on the load emission of the particulate pollutants. Compared with the
rainfall type III, first flush effects of pollutant loads of SS, COD, Cu, Pb, Cr,
Cd in rainfall type Iand type II were more obvious. Besides, first flush effect
of pollutant loads was not ubiquitous. All the pollutants in the monitoring 13
runoff events didn't exhibit an obvious first flush effect. The descending order
of the first flush effect of those pollutants was COD, SS, dissolved COD, Cu, Pb,
Cr, dissolved Cu, Cd, dissolved Pb, dissolved Cr, dissolved Cd.
PMID- 29964623
TI - [Inhibition of Internal Phosphorus Release in the Black-Odor Channel Under
Different Adding Methods of CaO2].
AB - The inhibition of sedimentary phosphorus(P) was investigated under the CaO2 with
3 addition ways. The overlying water and sediments came from a black-odor channel
in S City. The results showed that the value of pH and DO in the overlying water
increased under the 3 addition ways of CaO2. Under the condition of injection,
the DO concentration of the overlying water was lower than that of the covering
condition, which indicated that the injection could delay the oxidation of CaO2
and be favor of creating the micro-oxidation environment in the sediment. The
concentrations and the trend of TP and DIP in the overlying water were similar
under the injection and covering, which were lower than that in the mixing
condition. However, under the covering condition, the DIP concentration in the
pore water was the highest, reaching up to 120.33-142.18 times, compared with the
injection condition. Noticeably, the DIP in the pore water and the overlying
water was lower, indicating that the addition of CaO2 could inhibit the release
of sedimentary P. This was attributed to the micro-oxidation environment. The
sedimentary P fractions also confirmed this. The explanation may be that the
addition of CaO2 accelerated the mineralization of organophosphate and the
formation of Fe-Al/P and Ca-P, which enhanced the retention of sedimentary P.
PMID- 29964624
TI - [Transport of Nitrogen and Phosphorus from Sloping Farmland with Thin Purple Soil
Overlying Rocks].
AB - In a sloping farmland plot(1500 m2) of purple soil with underlying fractured
mudrock in Southwest China, field monitoring and sampling campaigns were
undertaken to explore the mechanisms of surface and subsurface transport of
nitrogen and phosphorus upon two representative rain events in the summer of
2015. The results indicated that:1depths of surface runoff and subsurface
fracture flow as well as average colloid export flux were dependent on antecedent
soil wetness and rainfall amount, while discharge dynamics and colloid peak
concentration were determined by rainfall intensity; 2nitrogen export was mainly
in dissolved forms through subsurface fracture flow, however, phosphorus was
mainly transported in particle-associated forms through surface runoff; 3the
transport of nitrogen and phosphorus was strongly influenced by hydrological
processes, with nitrogen and phosphorus transport being controlled by fracture
flow and surface runoff, respectively. Our findings contribute significantly to
the knowledge of nitrogen and phosphorus export from sloping farmland with thin
soil underlain by fractured rock upon rainfall, and on the other hand this study
provides reliable field data in support of developing effective approaches for
controlling agricultural non-point source pollution of N and P and identifying
key hydrological processes to be manipulated.
PMID- 29964625
TI - [Purification of Slightly Salt-alkaline Water Bodies by Microorganism Enhanced
Combined Floating Bed].
AB - In order to study the purifying effect of combined floating bed constucted by
salinity plant Suaeda salsa and microorganisms on the slightly salt-alkaline
water, blank floating bed A, S.salsa floating bed B, microbes floating bed C and
S.salsa + microorganisms combined floating bed D were established, and slightly
salt-alkaline eutrophic water body (pH 8.5-9.0, salinity 50/00-70/00) was
purified under continuous flow conditions in the laboratory. Results showed that
the removal rates of total nitrogen, total phosphorus, permanganate index by
S.salsa floating bed were 32.5%, 14.3% and 28.2%, respectively. And the removal
rates of total nitrogen, total phosphorus and permanganate index by S.salsa +
microorganisms combined floating bed D which installed artificial medium with
microorganisms reached 70.5%, 34.7% and 70.8%, respectively, of which the removal
rates of total nitrogen, total phosphorus and permanganate index by microbial
units were 37.7%, 21.6% and 44.5%, respectively. Synergies removal rates of
nitrate nitrogen and total nitrogen by S.salsa + microorganisms combined floating
bed were 12.2% and 0.3%, but there was no synergy in the process of removing
ammonia nitrogen, total phosphorus and permanganate index, which indicated that
the synergies of S.salsa and microorganisms in the combined floating bed were
suppressed in slightly salt-alkaline environment. The high-throughput sequencing
technique was adopted to analyze the microbial community in the floating bed C
and D, which indicated that the abundance and diversity of microbial community in
the combined floating bed were higher, and this was consistent with the result of
the higher removal rate of the flotation bed D. Principal component analysis
showed that the microbial degradation was a major factor in reducing the
concentration of pollutants. This study provided a guide for the using of
floating bed in purifying slightly salt-alkaline eutrophic water bodies in
coastal area.
PMID- 29964626
TI - [MgO-Biochar for the Adsorption of Phosphate in Water].
AB - A novel composite material MgO-biochar (MgO-BC) with the peanut shells as the
precursors was successfully fabricated by loading magnesium oxide (MgO) on the
surface of biochar (BC) at high temperature and in oxygen-limited atmosphere. The
adsorption characteristics of the resultant adsorbent toward phosphate from
aqueous solution were investigated by evaluating the influences of pH, contact
time and coexisting ions. The results showed that the best phosphate adsorption
onto MgO-BC happened in the pH range of 7-9, and strong acidic or basic media was
unfavorable to the phosphate adsorption. Phosphate adsorption process could reach
equilibrium within 540 min, and the kinetics curve could be well fitted by both
pseudo-first and pseudo-second models. The related coefficients were 97.3% and
99.0%. MgO-BC exhibited highly selective capacity toward phosphate in the
presence of competing Cl-, HCO3- and NO3- at 10 times higher concentration than
the phosphate concentration. In addition, phosphate adsorption onto MgO-BC could
be described satisfactorily by Langmuir model with a fitting coefficient of
higher than 99%, and the maximal adsorption capacity calculated by Langmuir
equation was 138.07 mg.g-1. The adsorption capacity of phosphate by MgO-BC was
much higher than the unmodified BC and other biochar-based sorbents. Furthermore,
the composite material after the adsorption of phosphate could also be used as a
fertilizer into the soil. It achieved the reuse of the discarded phosphate. All
the results validated that MgO-BC has a wide application prospect for the
phosphate cleanup from the actual wastewater.
PMID- 29964627
TI - [Degradation of N-nitrosodimethylamine by Palladium/ Iron Bimetallic Composite
Catalytic Fiber].
AB - N-nitrosodimethylamine (NDMA) in the water environment is a carcinogenic organic
contaminant, which can be converted to hypotoxic compounds by zero-valent iron
degradation. For the removal of trace NDMA in water, the theory and efficiency of
zero-valent iron degradation should be intensely researched. In this study, the
polypropylene (PP) fibers were chosen as substrate materials and the composite
catalyst fibers containing Pd/Fe0 bimetal were prepared by the UV irradiation
coordination method for the removal of trace NDMA. Pd/Fe0/PP-g-AA was
characterized by scanning electron microscope, inductively coupled plasma atomic
emission spectrometry, and X-ray photoelectron spectroscopy. The NDMA removal by
Pd/Fe0/PP-g-AA under different conditions was investigated. The results indicated
that when the acrylic acid monomer mass fraction was 20%, the composite catalytic
fiber Pd/Fe0/PP-g-AA showed a better degradation effect on NDMA. The removal of
NDMA followed the pseudo-first-order reaction kinetics model. The initial NDMA
concentration and the pH of the solution could not greatly influence the
catalytic degradation of trace amounts of NDMA. The presence of 3CO2- and NO3-
significantly inhibited the degradation of NDMA. However, the NDMA degradation
had been less affected by SO42-, HCO3-, and nature organic matter (NOM) existing
in the solution.
PMID- 29964628
TI - [Effects of Goethite, Magnetite and Gypsum on the Anaerobic Degradation of 2,4
Dichlorophenol].
AB - 2,4-dichlorophenol(2,4-DCP), a highly toxic and refractory organic compound, was
commonly used in pesticide production and thus widely distributed in water and
soil. Goethite, magnetite and gypsum were added into the anaerobic system which
simulated the natural anaerobic process to evaluate their effects on the
anaerobic degradation of 2,4-DCP. It indicated that goethite, magnetite and
gypsum had no appreciable adsorption ability toward 2,4-DCP under anaerobic
condition. Mass balance analysis showed that only the transformation of 2,4-DCP
to 4-chlorophenol(4-CP) occurred in all experimental groups. The addition of
sodium acetate doubled the reductive dechlorination rate of 2,4-DCP in comparison
with the groups without exogenous carbon source. The reductive dechlorination
rate of 2,4-DCP was enhanced by the addition of goethite and magnetite, which was
caused by the improved metabolic activity of dechlorination bacteria that played
an important role in the anaerobic degradation of 2,4-DCP. Gypsum greatly
inhibited or even stopped the degradation process of 2,4-DCP through restraining
the growth and activity of dechlorination bacteria. This study will shed light on
the migration and degradation of refractory chlorinated organic contaminants in
anaerobic sedimentary environment, and the treatment of such matters in
environmental technology.
PMID- 29964630
TI - [Treatment of PTA Wastewater by Modified Anode Microbial Fuel Cell].
AB - The purpose of this study was to investigate the effect of different modified
anodes on the microbial fuel cell(MFC) and the effect of MFC on the treatment of
refractory wastewater. Based on a single room air cathode, the anode of MFC was
modified by 0.10 g of tourmaline, 75% manganese bioxide/halloysite
nanotube(MnO2/HNT) and multi-walled carbon nanotube-carboxyl(MWCNT-COOH),
respectively. The results showed that, the removal rate of purified terephthalic
acid(PTA) was higher than 70%, and the chemical oxygen demand(COD) removal rate
was more than 79% in MFC with different modified anodes. Compared with others,
MFC with MWCNT-COOH modified anode obtained the maximum output voltage and
maximum power density, which were 529 mV and 252.73 mW.m-2, respectively.
PMID- 29964629
TI - [Transformation of Disinfection Byproduct Precursors During the Wastewater
Regeneration Processes].
AB - Disinfection byproduct(DBP) precursors during the wastewater regeneration
processes were separated into hydrophilic fraction(HPI), hydrophobic
fraction(HPO) and transphilic fraction(TPI) with macroporous resin. DBP
precursors in these water samples were characterized with fluorescence excitation
emission matrix, Fourier transformation infrared and nuclear magnetic resonance,
and were further tested for their DBP formation potential(DBPFP) after
chlorination. The results indicated that main DBP precursors in sewage were humic
acid and aliphatic hydrocarbons, and were mainly dominated by HPI. Primary
treatment(sedimentation) could effectively remove hydrophobic humic acid through
the mutual exclusion between HPO and water. The removal of humic acid would lead
to the obvious reduction of carbonaceous disinfection byproduct formation
potential(C-DBPFP). In addition, nitrogenous disinfection byproduct formation
potential(N-DBPFP) was found to be increased due to the increase of DON/DOC
value. Although secondary treatment(biotreatment) was effective in removing humic
acid and aliphatic hydrocarbons, it could produce a large amount of soluble
microbial products(SMP), which led to the enhancement of HPO percentage. And the
accumulation of SMP resulted in the significant increase of C-DBPFP and N-DBPFP.
Humic acid and hydrophobic SMP could be removed by the advanced treatment(cloth
filtration), leading to the reduction of HPO percentage and the increase of HPI
percentage. The decrease of humic acid and hydrophobic SMP would cause the
reduction of C-DBPFP and N-DBPFP in the advanced treatment.
PMID- 29964631
TI - [Selective Inhibition of Rice Straw Extract on Growth of Cyanobacteria and
Chlorophyta].
AB - Rice straw is supposed to be an environment-friendly biomaterial for inhibiting
the growth of harmful blooms of the cyanobacterium Microcystis aeruginosa. The
effects of rice straw extract(RSE) on algal growth, morphologic parameters(cell
size), and physiological parameters(in vivo Chl-a fluorescence) were investigated
using flow cytometry. We examined the selective inhibitory potential of rice
straw on four cyanobacterial strains(toxic and non-toxic Microcystis aeruginosa,
toxic Anabaena flos-aquae, and Microcystis ichthyoblabe), in comparison with
inhibitory effects on three common freshwater green algae(Selenastrum
capricornutum, Chlorella pyrenoidosa, and Scenedesmus obliqnus). Concentrations
from 2.0 to 10.0 g.L-1 of RSE were found to efficiently inhibit the growth of
cyanobacteria in a dose-dependent manner, simultaneously modifying the in vivo
Chl-a fluorescence and cell size. The 50% growth-inhibition concentration(7 d) of
A. flos-aquae, M. ichthyoblabe, M. aeruginosa(toxic strain), M. aeruginosa(non
toxic strain) was 1.72, 2.21, 2.92 and 5.72 g.L-1, respectively. Interestingly,
the growth and cell size of C. pyrenoidosa and S. obliqnus increased with the
addition of RSE and colony formation was observed. In the case of S.
capricornutum, the inhibitory effect of RSE on growth and in vivo Chl-a
fluorescence occurred at 1.0-4.0 g.L-1, while RSE induced a stimulatory effect on
algal growth at 8.0-10.0 g.L-1. Taken together, the sensitivity of cyanobacteria
to RSE was significantly higher than that of S. capricornutum, C. pyrenoidosa and
S. obliqnus. The higher sensitivity of PSII reaction center of cyanobacteria and
the ability to form colonies of green algae may have important implications for
the species-specific allelopathic antialgal activity of rice straw.
PMID- 29964632
TI - [Cultivation of Spirulina platensis in Digested Piggery Wastewater Pretreated by
SBR with Operating Conditions Optimization].
AB - Digested piggery wastewater(DPW) contains high concentrations of nitrogen and
phosphorus which could be used as a cost-effective culture medium for Spirulina
platensis. However, Spirulina platensis would be limited by many factors in the
complex composition of DPW, especially the high concentration of ammonium. In
this paper, a traditional sequencing batch reactor(SBR) was used to remove these
inhibitors in DPW. The retention of nitrate and nitrite in the effluent, which
was used as nitrogen source for cultivating Spirulina platensis, was studied at
different ratios of chemical oxygen demand(COD) to total nitrogen(TN) in the
influent. By comparing the growth of Spirulina platensis in the related
effluents, the operation condition of SBR was optimized. The lab-scale
cultivation results showed that Spirulina platensis possessed a high biomass
yield of 0.084 g.(L.d)-1 in the effluent when the COD/TN ratio of SBR influent
was 3.0. In particular, the concentrations of ammonium, nitrate and nitrite in
the effluent were 51.2 mg.L-1, 91.6 mg.L-1and 213.1 mg.L-1, respectively.
Furthermore, the aforementioned effluent was also used to culture Spirulina
platensis in a 120 L outdoor raceway pond, and the growth rate of Spirulina
platensis reached(0.075+/-0.003)g.(L.d)-1 after 10-day culture. The protein
content of Spirulina platensis was approximately 60% and the removal efficiency
of ammonium was 99%. This study provides an alternative method for the
utilization of DPW.
PMID- 29964633
TI - [Nitrogen Removal Performance of ANAMMOX Process with K+ Addition in Saline
Surroundings].
AB - In view of the poor performance of biological nitrogen removal in saline
wastewater treatment, nitrogen removal of anaerobic ammonium oxidation(ANAMMOX)
with K+ addition was studied. The results showed that K+ addition could
strengthen nitrogen removal performance. The effect of K+ on ANAMMOX process was
mainly divided into four stages. In the adaptive phase(0-2 mmol.L-1), sudden
addition of K+ destroyed the original equilibrium reaction, but ultimately
ANAMMOX bacteria could adapt to the presence of K+. Because K+ had no obvious
effects on anaerobic ammonia oxidation bacteria, the removal rates of NH4+-N and
NO2--N slightly increased. In the ascension phase(2-8 mmol.L-1), K+ played a role
in promoting anaerobic ammonia oxidation biological systems, with increasing
concentration of K+, the removal rates of NH4+-N and NO2--N significantly
increased. In the stabilization phase(8-20 mmol.L-1), the nitrogen removal rate
decreased, but was still higher than the control without K+ addition. In the
inhibition phase(more than 20 mmol.L-1), K+ largely inhibited anaerobic ammonia
oxidation, and its denitrification efficiency was lower than 0 mmol.L-1. In the
whole cycle, when the concentration of K+ was 8 mmol.L-1, it achieved the best
effect, the average removal rates of NH4+-N and NO2--N were 89.24% and 84.87%,
and NRR was 1.113 kg.(m3.d)-1.
PMID- 29964634
TI - [Efficient and Stable Operation of Shortcut Nitrification by Entrapping Ammonia
Oxidizing Bacteria].
AB - In order to improve the efficiency of shortcut nitrification by entrapping
ammonia oxidizing bacteria, the technique of ammonia oxidizing bacteria(AOB)
enrichment culture was studied. The continuous operation method was used to
inhibit the growth of nitrite-oxidizing bacteria(NOB) by free ammonia, at the
same time, the NOB was gradually washed out of the system through the technology
of sludge discharge. Polyvinyl alcohol(PVA) was used as the embedding material to
immobilize the ammonia oxidizing bacteria after enrichment culture. The embedding
rate of the reactor was 8%. The ammonia oxidation rate was increased by improving
ammonia nitrogen loading in the continuous operation mode. The results showed
that the ammonia oxidation rate(NH4+-N/VSS)was as high as 2.028 g.(g.d)-1 and the
nitrite nitrogen accumulation rate was stabilized at more than 90%. High
throughput sequencing analysis was conducted on the bacterial community
composition before and after enrichment culture, and the experimental result
indicated that the culture diversity of raw sludge was larger. Nitrosomonas and
Nitrospirae, which have nitrification function, accounted for 0.24% and 2.7%,
respectively. The diversity of the activated sludge decreased significantly after
the enrichment culture, Nitrosomonas(18%) became the dominant bacteria whereas
Nitrospira occupied only 0.02%. After he embedding of ammonia oxidizing bacteria,
the shortcut nitrification was realized rapidly. Finally, the shortcut
nitrification rate reached 50 mg.(L.h)-1and the nitrite nitrogen accumulation was
above 90%.
PMID- 29964635
TI - [Fast Start-up of ANAMMOX and the Spatial Distribution of EPS in ANAMMOX
Granules].
AB - An anaerobic sequencing batch reactor(ASBR) inoculated with activated sludge was
employed to investigate the start-up of anaerobic ammonium oxidation(ANAMMOX)
process and the spatial distribution of extracellular polymeric substances(EPS)
in ANAMMOX granules. The results showed that the removal rates of NH4+-N and NO2-
N reached more than 99%. The removal rate of total nitrogen(TN) was 89.87%+/
0.43% and the TN removal load in the ASBR was 1.7 kg.(m3.d)-1. The ratios of
nitrite consumption and nitrate production to ammonium consumption were 1.32+/
0.08 and 0.24+/-0.03, respectively. Besides, the pH and the effluent nitrate
concentration in bulk liquid were considered as two simple indicators for rapid
diagnosis of ANAMMOX performance. The proteins(PN) was the main component of EPS
in ANAMMOX granular sludge. The PN and polysaccharides(PS) in ANAMMOX granules
were (59.61+/-5.64) mg.g-1 and (12.21+/-2.04) mg.g-1, respectively, with the
ratio of PN/PS reaching approximately 4.88+/-1.39. beta-D-glucofuranose and dead
cells were distributed in the outermost layer of granules, while living cells,
PN, lipids, alpha-glucosamine and alpha-mannose were distributed throughout the
granules and mainly concentrated on the outside of granules. PN and lipids
constituted the framework of ANAMMOX granules and ANAMMOX bacteria were embedded
among the PN and lipids matrix.
PMID- 29964636
TI - [Ammonia Oxidation with Potential Electron Acceptor in ANAMMOX Sludge].
AB - The ammonium oxidation by potential electron acceptors(NO2-, Fe3+ and SO42-) in
ANAMMOX sludge was studied by inoculating nitrite-dependent ANAMMOX sludge. The
results showed that nitrite was the most suitable electron acceptor for ANAMMOX
bacteria, which could completely react within a short time. Nitrate was converted
into nitrite by ANAMMOX sludge using the organic as electron donor and then
participated in ammonia conversion, in the absence of nitrite. Fe3+ and SO42-
conversion occurred at the end of ammonium oxidation, but its direct or indirect
participation requires further study. Microbial activity must be activated
through addition of nitrite as electron acceptor before ammonia excess oxidation
occurred. Aerobic ammonia oxidizing bacteria and nitrite oxidizing bacteria grew
during this period. This phenomenon did not last, and the microbial production of
H2O2 was speculated. Although the oxidation rate was slow, the phenomenon of
ammonium excess oxidation was obvious. Therefore, the oxidation of excess ammonia
was for sure present in ANAMMOX sludge. The order of electron acceptor use by
ANAMMOX sludge was NO2-, NO3-, SO42- and Fe3+.
PMID- 29964638
TI - [Extensive Green Roof Substrate Composition Based on Sludge Recycling].
AB - The experiment was carried out to study the reasonable composition of stable
anaerobic sludge in the extensive green roof growth substrate by a total of 650
mm artificial rainfall event. Combined with the N, P leaching problem of the
sludge resources utilization, the quality of the effluent and the change of the
nutrient content of the substrate in the process of application were
investigated. The results showed that the anaerobic sludge could significantly
increase the plant biomass and the average weight gain was 808%. Stable anaerobic
sludge caused a large amount of leaching of TP and water treatment residual could
effectively control TP leaching and did not affect the absorption of P to the
plant. During the experiment, the TP of the effluent was reduced by 68.66%.After
stabilization, the effluent TP reached the surface water V standard. The main
form of leached TN was NO3--N and the leaching of NO3--N could be reduced by rice
husk charcoal. In the experiment, the NO3- -N leaching mass was reduced by 28.86%
totally. Increasing the amount of rice husk charcoal helped to control NO3--N
leaching. SS and COD could be quickly decreased and stabilized. The COD of
effluent after stabilization was about 30 mg.L-1, which was better than the
standard of surface water V. Under the condition of actual precipitation with
medium and small rainfall, the anaerobic sludge nutrient retention time should be
more than 1 year, which meets the growing needs of plants for a long time.
PMID- 29964637
TI - [Ammoniac Waste Gas in-situ Treatment Based on ANAMMOX Process].
AB - The feasibility of ammoniac waste gas in-situ treatment by partial
nitrification(PN)-anaerobic ammonia oxidation(ANAMMOX) reactor was studied. The
PN-ANAMMOX reactor was successfuly started up after 60 d operation in conditions
of low dissolved oxygen control(0.2 mg.L-1), pH 7.9-8.2 and temperature(30-35C).
The total nitrogen removal efficiency reached 88% and the nitrogen removal rate
increased from 0.05 kg.(m3.d)-1 to 0.7 kg.(m3.d)-1. In the treatment of ammoniac
waste gas, the excess oxygen in it would lead to massive growth of nitrifying
bacteria, when the ammonia concentration was lower than 2.59%. The ammonia and
oxygen in waste gas met the requirement of the reactor for nitrogen removal, when
the ammonia concentration stayed between 2.59% and 4.2%. Extra air flow was
required for reactor oxygen supplement when the ammonia concentration was higher
than 4.2%. The ammonia removal efficiency reached 100%, the total nitrogen
removal efficiency reached 90.06%, while the total nitrogen removal rate was 0.51
kg.(m3.d)-1 after 60 day operation for ammoniac waste gas purification. It is
indicated that the integrated reactor based on PN-ANAMMOX process can achieve
stable removal of ammonia waste gas.
PMID- 29964639
TI - [Short-term Effect of Roxithromycin on Abundance and Diversity of Ammonia
Oxidizing Microorganisms in Activated Sludge].
AB - In this study, the short-term effect of roxithromycin(ROX) on the abundance and
diversity of ammonia-oxidizing archaea(AOA) and ammonia-oxidizing bacteria(AOB)
based on amoA gene in activated sludge were investigated by high-throughput
sequencing and quantitative real-time PCR(qPCR). High-throughput sequencing
overcomes the drawbacks of low sequencing depth, significant randomness and great
bias of traditional Sanger sequencing. This approach can provide enough
sequencing depth to comprehensively investigate the sensitive and insensitive
ammonia-oxidizing microorganisms under ROX selective pressure. Lab-scale reactors
were operated under ten different ROX levels. The results indicated that the
environmental(0.3-30 MUg.L-1) and medium(300 MUg.L-1and 3000 MUg.L-1) levels of
ROX did not affect ammonia oxidation, while the higher concentration(5000-12000
MUg.L-1) of ROX showed a significant negative effect on ammonia oxidation. The
environmental and medium levels of ROX stimulated the growth of AOA, however, the
higher level of ROX decreased the abundance of AOA. In addition, different levels
of ROX(except 0.3 MUg.L-1) caused the decrease of the abundance of AOB, which
suggested that AOA was less sensitive than AOB under ROX selective pressure. The
results of high-throughput sequencing showed that ROX selective pressure caused
the decrease of the numbers of OTUs for AOA and increase of that for AOB. The
insensitive AOA, accounting for 57.70%-97.81% of the total sequences, were
Candidatus Nitrososphaera gargensis and Candidatus Nitrosoarchaeum koreensis. The
insensitive AOB were Nitrosomonas oligotropha, Nitrosospira multiformis,
Nitrosomonas watsonii and Nitrosomonas halophilus, accounting for 0.76%-5.10% of
the total sequences. These results also indicated that AOA was insensitive to
ROX, but AOB was sensitive to ROX. RDA analyses showed that AOA Ca.
Nitrososphaera gargensis, Ca. Nitrosoarchaeum koreensis and AOB N. oligotropha,
N. watsonii, N. halophilus were positively correlated with ROX concentrations.
PMID- 29964640
TI - [Influence of Salinity on Microbial Community in Activated Sludge and Its
Application in Simulated Dye Wastewater Treatment].
AB - The performance and microbial community profiles in a sequencing batch
reactor(SBR) treating saline wastewater were studied over 300 days from 0% to
2.0% salinity. The effects of crystal violet wastewater and nano-ferroferric
oxide on microbial communities were also researched. The experimental results
indicated that the activated sludge had high sensitivity to salinity variations
in terms of pollutants removal and sedimentation. At 2.0% salinity, the system
retained a good performance, and 80% removal rate of COD and 75% removal rate of
NH4+-N could be achieved and SVI value was less than 35 mL.g-1; With the increase
of salinity, the microbial diversity reduced gradually, the advantageous position
of Gram-negative bacteria was gradually replaced by fungi and actinomycetes,
whereas Gram-positive bacteria strains remained the advantageous group; In the
comparison of activated sludge added with crystal violet dye with the activated
sludge samples with a salinity of 2%, it was found that the contents of
Parvibaculum and Winogradskyella were higher while the contents of Rhodanobacter
and Agrobacterium decreased. In the comparison of crystal violet-activated sludge
with and without addition of MNPs, it was found that the contents of Acidocella
and Rhodanobacter were higher while the contents of Parvibaculum and
Agrobacterium decreased.
PMID- 29964641
TI - [Shift of Microbial Communities During the CO2-Brine-Sandstone Interaction
Process].
AB - In this study, the dynamic variation of the structure, functionality and
biodiversity of indigenous microorganism during the CO2-brine-sandstone
interaction process was investigated using MiSeq sequencing techniques. The
results indicated that some kinds of indigenous microorganisms could grow well
under the extreme condition induced by CO2-injection. After injection of CO2, the
species of indigenous microorganisms tended to be single and the relative
abundance of Proteobacteria reached up to 99.77% after 6 months. The dominant
species varied as follows:Pseudomonas sp., Citrobacter sp. and Brevundimonas sp..
Meanwhile, some special genera such as Bacillus sp., Hydrogenophaga sp. and
Rhizobium sp. with functionality of iron-reducing and denitrification were found
in this study, which may have a potential effect on the capture and storage of
CO2. In addition, the Shannon index decreased from 5.3302 to 1.9465 after
injection of CO2, suggesting that the biodiversity reduced significantly.
Function and main metabolites analysis of bacteria in the CO2-brine-sandstone
interaction process showed that bacteria like Bacillus sp., Citrobacter sp. and
Pseudomonas sp. could enhance CO2 solubility-trapping process. Bacteria
metabolisms could accelerate the dissolution of feldspar and chlorites, and
facilitate the formation of transition-state calcite and siderite. Otherwise, the
great variation was mainly attributed to the change of condition driven by CO2
brine-sandstone interactions, such as pH and the chemical composition of brine
water(anion and cation), etc.
PMID- 29964642
TI - [Response of Soil Respiration and Heterotrophic Respiration to Returning of Straw
and Biochar in Rape-Maize Rotation Systems].
AB - Soil respiration has become the main way of farmland ecosystem carbon emissions.
Soil respiration and its responses to soil moisture and soil temperature under
straw and biochar returning were investigated. Combined soil CO2 fluxes
system(ACE-002/OPZ/SC) with the method of root exclusion, this study conducted a
long-term field experiment in the national monitor station of soil fertility and
fertilizer efficiency of purple soils. The total soil respiration and
heterotrophic respiration rate and the soil hydrothermal factors were measured
during the growth period of rape and maize in rape-maize rotation systems, and
the difference between total soil respiration and heterotrophic respiration was
calculated as the contribution of root respiration to soil respiration. There
were five treatments including CK(no organic material), CS(straw),
CSD(straw+microorganism), BC(biochar), CSBC(50%straw+50%biochar), which were
replicated three times. The results showed that straw and biochar returning
significantly affected the seasonal variations and the peak of soil respiration.
In addition to BC treatment, other treatments promoted soil respiration and
cumulative emissions of soil CO2. Soil respiration rate was significantly
different under different treatments, the changes in soil respiration rates
showed a single peak curve under all treatments, the seasonal variations in soil
respiration rates under rape was 0.12-2.29 MUmol.(m2.s)-1, displaying an order of
CS > CSD > CSBC > CK > BC. Soil respiration was pretty complex in maize season,
the seasonal variation in soil respiration rates under rape was 1.02-15.32
MUmol.(m2.s)-1, displaying an order of CSD > CS > CSBC > CK > BC, the changes in
soil respiration rate presented a double peak curve under CS and CSD and CSBC
treatments and a single peak curve under BC and CK treatments. Heterotrophic
respiration could explain 86.50%-93.94% of seasonal variations in the soil total
respiration, and the contribution of root respiration(26.49%-32.86%) was
significantly lower than CK treatment(53.65%).Straw and biochar returning did not
change soil temperature and soil moisture. Soil temperature at 5 cm depth had
significant effects on the change dynamics of soil respiration rates, but soil
moisture did not. Soil temperature at 5 cm depth could explain 82%-94% of the
variations in soil respiration. The values of temperature sensitivity coefficient
changed from 3.28 to 4.47. Compared with CK treatment, Q10 of CS, CSD and CSBC
decreased by 26.62%, 18.12%, 20.58%, respectively, while BC increased by 12.53%.
There was no synergistic effect between soil temperature and soil moisture on
soil respiration, the dynamic changes of soil respiration rate could be simulated
by single factor index function of soil temperature. Overall, soil respiration
was significantly promoted by returning of straw, straw+microorganism,
straw+biochar, while it was inhibited by returning of biochar.
PMID- 29964643
TI - [Effect of Simulated Climate Warming on Microbial Community and Phosphorus Forms
in Wetland Soils].
AB - Microbial community and phosphorus forms in response to simulated climate warming
were studied by high-throughput sequencing and 31P nuclear magnetic resonance(31P
NMR) respectively, which were from wetland soils in constructed microcosm
columns. The results revealed that relative abundances of Firmicutes, Clostridia,
Clostridiales, Clostridiaceae and Clostridium were significantly decreased by 65%
98%, 69%-87%, 67%-87%, 73%-97% and 74%-93% under warming condition respectively,
suggesting warming had a significant inhibitory effect on the bacterial lineage
from Firmicutes to Clostridium at different taxonomic level. Particularly,
principal coordinate analysis and cluster analysis also demonstrated warming had
a significant effect on microbial community structure with obvious separation of
samples between control and warmed groups from each wetland column site.
Phosphorus forms were dominated by phosphomonoester and orthophosphate in each
wetland column soil, which were significantly increased and decreased by 275% and
20% in XX wetland column soil respectively. Similarly, phosphomonoester and
polyphosphate were also found to be increased and decreased by 85% and 49% in JH
wetland column soil respectively, indicating that phosphorus forms in response to
warming had soil heterogeneity. Canonical correspondence analysis showed that
obvious changes in microbial community composition had significant effects on
phosphorus forms under warming condition.
PMID- 29964644
TI - [Patterns of Bacterial Community Through Soil Depth Profiles and Its Influencing
Factors Under Betula albosinensis Burkill in the Xinjiashan Forest Region of
Qinling Mountains].
AB - In this study, vertical changes in bacterial alpha-diversity and community
composition were investigated at four soil depths(0-10, 10-20, 20-40 and 40-60
cm) in Betula albosinensis Burkill forest of Qinling Mountains by sequencing of
the 16S rDNA regions using Illumina MiSeq high-throughput technology. The results
showed that the decreases of OTUs, Chao1 and Shannon were numerical but not
significant, and the highest values of 1688, 2314 and 8.66 were obtained in 0-10
cm, respectively. At the phylum level, Acidobacteria and Proteobacteria were the
most dominant bacteria in four soil layers. At the genus level, Gp4, Gp6 and Gp16
were the most dominant bacteria. The relative abundance of Acidobacteria in 40-60
cm soil depth(62.88%) was higher than those in other soil depths. Proteobacteria
in 0-10 cm(23.62%) was more abundant than that in 40-60 cm. The relative
abundance of Acidobacteria was significantly correlated with the total N, soil
organic carbon, C/N, and soil dissolved organic carbon. Soil water content, soil
organic matter and soil dissolved organic carbon were the key factors affecting
soil Proteobacteria. RDA sequencing results showed that soil dissolved organic
carbon was the key factor contributing to the bacteria community abundance. The
results demonstrated that there are plenty of bacterial distribution in all four
soil layers, which provides a fundamental basis for vertical soil bacterial
community diversity, and possesses very important research value in
biogeochemical cycling.
PMID- 29964645
TI - [Effects of Microbial Activities on Mercury Methylation in Farmland near Mercury
Mining Area].
AB - In order to study the main effect of microbial activities on mercury(Hg)
methylation in farmland, mercury contaminated upland soils and paddy soils near
Hg mining area were sampled as experimental soils. Four treatments were designed
including only sterilization as the control, accelerating the activities of
sulfate reducing bacteria(SRB), inhibiting the SRB's activities, and accelerating
the activities of iron-reducing bacteria(FeRB), to know the effects of microbial
and non-microbial factors on mercury methylation in soils. The results were as
follows:the highest concentration of methylmercury(MeHg) was observed in soils
with SRB accelerated treatment, and the increments of MeHg concentrations in
upland soils and paddy soils ranged from 0.15 MUg.kg-1 to 0.38 MUg.kg-1 and 1
MUg.kg-1 to 2 MUg.kg-1, respectively. Comparatively, little increments of MeHg
concentration were seen in soils with SRB inhibited treatment and FeRB
accelerated treatment, which were lower than 0.025 MUg.kg-1. Compared with upland
soils, more MeHg was formed in Paddy soils and the concentrations of MeHg in
paddy soils were 4-9 times of that in upland soils. Variation in the number of
SRB in soils was similar to that in the concentration of MeHg in soils, and the
number of SRB was positively correlated with the concentration of MeHg
concentrations in soils(R2=0.57,P<0.01). The above results indicated that
activities of reducing bacteria, especially SRB, played key role in the
methylation in soils. In addition, more attention should be paid to paddy soils
due to the high potential of methylation when conducting any assessment and
taking any measure to manage the health risk caused by the exposure to mercury.
PMID- 29964646
TI - [Effect of Sepiolite Application on the Migration and Redistribution of Pb and Cd
in Soil Rice System in Soil with Pb and Cd Combined Contamination].
AB - In order to research the coordination relation between sepiolite application and
the contents of available lead(Pb) and cadmium(Cd) in soil or rice absorption and
redistribution of Pb and Cd, a pot experiment was conducted by selecting the soil
sampled from a area polluted by Pb and Cd combination in Shaoxing City of
Zhejiang Province and atypical late Japonica Rice Varieties in Zhejiang
Province(Jia 33) with lower accumulation for Pb, Cd. The results showed that:the
contents of available Pb and Cd in soil were significantly negatively correlated
with the concentration of sepiolite added, the correlation coefficients of
contents of available Pb and Cd with the concentration of sepiolite added were
0.940 respectively and -0.952, which reached the significant level(P<0.01).The
contents of Pb and Cd in rice roots, stems, leaves and polished rice had
different reducing rates with the increase of the concentration of sepiolite. In
addition, with the increase of the concentration of sepiolite added, the
enrichment coefficients of Pb and Cd in rice roots, stems, leaves and polished
rice decreased dramatically. At the same time, Pb and Cd absorbed by roots
transferred to the stems decreasingly, Pb and Cd absorbed by stems transferred to
the polished rice decreasingly. When the addition of Sepiolite was 9.00 g.kg-1
soil, the contents of Pb and Cd in polished rice of Jia 33 were(0.14+/-0.02)
mg.kg-1 and(0.03+/-0.01) mg.kg-1 respectively, which were all lower than the
national limit index(GB 2762-2012). Compared with the control group, the
enrichment coefficients of Pb in roots, stems and leaves and polished rice
decreased by 8.83%, 29.96%, 49.20%, 79.41% respectively, and the enrichment
coefficients of Cd decreased by 23.08%, 63.22%, 44.00%, 82.35% respectively. In
addition, the transportation coefficients of Pb and Cd absorbed by roots transfer
to the stems were decreased by 23.18% and 52.19% respectively and the
transportation coefficients of stem rice translocation of Pb and Cd absorbed by
stems transfer to the polished rice were decreased by 70.83%, 52.00%,
respectively. This result means the sepiolite had a good resistance control in
the migration and redistribution of Pb and Cd in soil rice system on the soil
polluted by lead and cadmium, indicating the combination of rational application
of sepiolite and rice varieties with lower accumulation for heavy metals can
achieve safe agricultural utilization of the soil with combined contamination by
a relatively higher concentration of Pb and Cd.
PMID- 29964647
TI - [Application of Amphoteric-Cationic Combined Modification on Phenol Adsorption of
Yellow Brown Soil].
AB - Based on the best modification ration of adsorption of phenol on montmorillonite
modified by a mixture of amphoteric modifier, dodecyl dimethyl betaine(BS-12),
and cationic modifier, hexadecyltrimethyl ammonium bromide(CTMAB),an experiment
was designed to prepare two series of amphoteric-cationic modified soils by two
yellow brown soils with montmorillonite contents of 43% and 6%,respectively. The
adsorption properties of phenol were studied, and the adsorption influence at
different temperature, pH and ionic strength was also analyzed and moreover, the
adsorption differences between co-modified montmorillonite and yellow brown soils
and between two co-modified yellow brown soils were discussed by comparing with
co-modified montmorillonite. The results showed that adsorption of yellow brown
soils as well as co-modified montmorillonite on phenol increased with combined
modification, adsorption capacity was in order of 215BS+215CT(215%BS
12+215%CTMAB) > 215CT(215%CTMAB) > 215BS(215%BS-12) > CK1(unmodified soil
containing montmorillonite content of 43%),33BS+33CT(33%BS-12+33%CTMAB) >
33CT(33%CTMAB) > 33BS(33%BS-12) > CK2(unmodified soil with montmorillonite
content of 6%) at 30C.Henry model described the adsorption of phenol very well.
The phenol adsorption of modified yellow brown soils decreased with increasing
temperature and pH, but increased with increasing ionic strength at low
concentration ranges as well as modified montmorillonite. The basic reason for
adsorption difference between co-modified montmorillonite and yellow brown soils
and between two co-modified yellow brown soils was Cation Exchange Capacity(CEC).
PMID- 29964648
TI - [Bioaccumulation of Heavy Metals in Twigs and Leaves of Abies fabri at Mount
Gongga in China: A Comparison Study Between 1999 and 2014].
AB - The rapid economy growth led to the environmental carrying capacity reaching the
maximum level.Given that the time changing trend of heavy metal pollution in the
remote forest ecosystems has rarely been reported, we reported the differences of
Pb, Hg, Cd, As, Cr, Mn, Cu, Zn and bioaccumulation in twigs and leaves of
fir(Abies fabri) between samples collected in 1999 and 2014 at the Mt. Gongga,
which was located at eastern Tibet Plateau. Our results suggested that the
concentrations of Pb, Hg, As, Cd, Mn and Cu in the samples collected in 1999 were
significantly higher than those collected in 2014, while the concentrations of
Cr, Zn and Ba in samples collected in 2014 were higher than those collected in
1999. The correlation analysis indicated that concentrations of Pb, Hg, Cr, As,
Cd, Mn, Cu, Zn and Ba in leaves were positive correlated to the age of the
leaves. In addition, Hg was apt to enrich in leaves while the other metals were
prone to enrich in twigs. According to the multiple linear regression result,
about 70.6% of Hg in leaves and twigs was from air, while the other heavy metals,
including Pb, Cr, As, Cd, Cu, Zn, and Ba, were mainly from soil(42.3%-92.2%).
These results suggest that there may be different accumulation mechanisms in
forest ecosystems between Hg and the other heavy metals.
PMID- 29964649
TI - [Subcellular Distribution and Chemical Forms of Heavy Metals in Three Types of
Compositae Plants from Lead-Zinc Tailings Area].
AB - Field investigation on the content of heavy metals in soils and three types of
widely distributing compositae plants(Artemisia lavandulaefolia, Ageratum
conyzoides L., Crassocephalum crepidioides) in lead-zinc tailings farmland of
Yangshuo, Guangxi Zhuang Autonomous Region was carried out, and the differential
centrifugation technique and sequential chemical extraction method were used to
study the subcellular distribution and chemical forms of heavy metals in these
plants. The results indicated that the soil in the tailings farmland was highly
contaminated by Cd, Pb and Zn, and their concentrations were 37.7, 5.7 and 8.9
times higher than their respective values of national standard for soil
environment quality(GradeII). The contents of Cd, Pb and Zn in the analyzed
plants exceeded the normal ranges. Ageratum conyzoides L. and Crassocephalum
crepidioides showed strong capability in tolerance, accumulation and transport of
Cd, and they could be used as pioneer plants for Cd-phytoremediation in study
area and some related areas. In addition, Cd concentrations in the stem and leave
of Crassocephalum crepidioides were 159.6 mg.kg-1 and 219.5 mg.kg-1,
respectively, which exceeded the threshold of Cd hyperaccumulator. Thus,
Crassocephalum crepidioides can be regarded as a Cd-hyperaccumulator. Majority of
total Cd, Pb and Zn were found in soluble fraction and cell wall in the plants,
while only a small quantity were distributed in organelles. As for chemical forms
distribution, Cd, Zn and Pb predominated NaCl-, HAC-, and HCl-extractable forms
both in roots and shoots of the plants. Therefore, cell wall binding, vacuolar
compartmentalization and distribution mainly in lower active chemical forms were
supposed to be the main mechanisms for tolerance to heavy metals in the study
plants. A difference of Cd subcellular distribution and its chemical forms in the
three Compositae plants was observed. Compared with the shoot of Artemisia
lavandulaefolia, more Cd was located in the vacuolus and cellular soluble parts
in Ageratum conyzoides L. and Crassocephalum crepidioides. Moreover, the
proportion of active chemical Cd in the shoots was lower than that in the roots.
These results showed that the subcellular distribution and chemical forms of Cd
were related to the plant species,and also indicated Ageratum conyzoides L. and
Crassocephalum crepidioides were likely to possess a higher tolerance and
accumulation of Cd.
PMID- 29964650
TI - [Effects of Bentonite Amendment on Detoxification, Heavy Metal Passivation and
Estrone Elimination of Sewage Sludge Compost].
AB - Sewage sludge was amended with calcium-based bentonite with addition of no more
than 10% in dry weight during the 52-day aerobic composting process, the
variations of temperature, pH, organic carbon, EC, total nitrogen, nitrate(NH4+
N) and ammonium(NO3--N) were investigated, as well as the compost
detoxification(germination test), heavy metals(Zn, Cu, Pb, Cd) passivation and
estrone(E1) elimination. The results showed that the amendment facilitated the
thermophilic phase, promoted the compost heat inactivation and brought the
organic carbon mineral up to more than 15.27% -19.71%. During the composting, the
compost pH increased at the beginning and then gradually decreased before
reaching values of 6.76-7.05, while the amendments alleviated the dramatic pH
value fluctuation. The bentonite amendment reduced the salinity of the compost
with final product EC remarkably lower than 1132 MUS.cm-1 of the control
treatment, and the effect was enhanced with the increase of addition amount. The
total nitrogen content increased with time, and there was a remarkable ammonia
loss in the beginning stage for the control treatment, while the bentonite
addition could facilitate the total nitrogen content increase by reducing the
ammonia loss. With the composting variation, the contents of NH4+-N increased and
then decreased while the NO3--N content increased gradually. The bentonite
addition had a slight inhibitory effect on the plant germination but did not
influence the compost maturity and detoxification; meanwhile, the amendment
improved the heavy metal passivation and reduced the E1 content, especially from
90.48 to 28.27 MUg.kg-1 with 5% treatment during the composting. The study
indicated that bentonite addition of lower than 5% was acceptable for the sludge
compost amendment, which had great potential in sludge hygienization,
detoxification, heavy metal passivation and E1 elimination.
PMID- 29964651
TI - [Mesophilic and Thermophilic Anaerobic Co-Digestion of Food Waste and Straw].
AB - The anaerobic co-digestion of food waste and straw is more efficient in avoiding
the accumulation of volatile fatty acids and promoting the degradation of
lignocellulose in comparison with their individual digestions. The co-digestion
of food waste and straw was investigated under mesophilic(35C) and
thermophilic(55C) condition, respectively. The results indicated that when
feeding volatile solid concentration was 3 kg.m-3, the accumulated methane
production yield of the mesophilic reactor reached the peak of 272.0 mL.g-1 at a
food waste-to-straw ratio of 9:1, while it reached the peak of 402.3 mL.g-1 at a
food waste-to-straw ratio of 5:5 for thermophilic reactor. These amounts were
significantly higher than those of food waste digestion alone(218.6 mL.g-1 for
mesophilic reactor and 322.0 mL.g-1 for thermophilic reactor). Co-digestion
promoted the rate of carbon transfer to methane, and further, the rate of the
thermophilic reactor was higher than that of the mesophilic reactor. Degradation
rate for lignocellulose of thermophilic reactor was 34.7%-45.8%, higher than that
of mesophilic reactor, 12.6%-42.2%. It was confirmed by 16S rRNA gene sequences
of bacteria and archaea, ITS sequences of fungi based on high-throughput
sequencing techniques, which showed the amounts of lignocellulose degrading
bacteria and actinomycetes in the thermophilic reactor were both higher than
those in the mesophilic reactor.
PMID- 29964652
TI - [Basic Features of Combustible Rural Garbage Component and Its Spatial-temporal
Difference in China].
AB - In order to realize the disposal feasibility of rural garbage by incineration, 72
rural garbage sampling points of 12 provinces in China were chosen to analyse
mass fraction of full component and combustible component, moisture content of
full component and low heating value of rural garbage in spring, summer, autumn
and winter of 2015. The results revealed that the mass fraction of combustible
rural garbage components in wet basis followed the order of kitchen residual(13%
53%) > the rubber(10%-18%) > the paper(10%-15%) > the wood(0-10%) > the fabric(0
8%). The compositional difference of rural garbage was not apparent between
villages and towns within the same administrative region. The average moisture
content of full component in southern rural garbage was higher than that in
northern area, and the average moisture content of national rural garbage was
about 40.1%. The low heating value of rural garbage in full composition which
surpassed 3500 kJ.kg-1 was more than 81% in the north China, but in the south
China, it was 44%, 50%, 61% and 72% in spring, summer, autumn and winter,
respectively. After sorting, the low heating value increased greatly, but the low
heating value of southern rural garbage in spring was still less than 3500 kJ.kg
1, more than 56% towns and villages of southern rural garbage in summer, autumn
and winter and annual northern rural garbage heating value met the heating value
requirement of incineration disposal. Therefore, after sorting, the rural garbage
by incineration disposal method was feasible to the north China rural garbage,
but the south China rural garbage requires strengthened pretreatment process.
PMID- 29964653
TI - [Optimization of Promoter and Support for Co-based/zeolites Catalysts in
Catalytic Reduction of NOx by CH4].
AB - Catalytic behavior of Co-based/zeolites catalysts was investigated in NOx
reduction by CH4. Optimization of promoter and support was investigated by
catalytic tests, and the relationship between catalytic activity and catalyst
structure was illustrated by catalyst characterization. Co-Fe/SAPO-34 exhibited
the highest activity among various Co-base/zeolites catalysts. The maximum
conversion of NOx with 52.7% was obtained on Co-Fe/SAPO-34 at 450C. The
inhibition of activity of Fe/zeolites became severe in the presence of SO2, CO2,
and H2O. CO2 exerted virtually no effect on the SCR activity of Co-Fe/zeolites.
The inhibition of NOx conversion by H2O was reversible for Co-Fe/zeolites
catalysts. Cobalt species were mainly present in CoO and Co(OH)2 states in Co
Fe/SAPO-34. Co3O4and Co(OH)2 were the main cobalt species of Co-Fe/ZSM-5, while
CoO, CoAl2O4 and Co3O4 might be present in Co-Fe/Beta. The ratio of Fe2+/Fe3+ in
the surface layer of Co-Fe/zeolites decreased in the order of Co-Fe/ZSM-5(3.98) >
Co-Fe/SAPO-34(0.52) > Co-Fe/Beta(0.43). The active states of cobalt species and
suitable ratio of Fe2+/Fe3+ were important for the activity of Co-Fe/zeolites in
CH4-SCR. CH4-SCR over Co-Fe/zeolite catalysts started with the adsorption of NO
and CH4 on Bronsted acid sites of the zeolite to produce NO+and carbon-containing
species(-C=O and -COO) in the presence of oxygen, respectively. Subsequently, the
important intermediates of nitrate species were generated from NO+ at the active
sites. Finally, nitrate species reacted with carbon-containing species to form N2
and CO2.
PMID- 29964654
TI - [Air Pollutant Emission Inventory and Impact of Typical Industries on PM2.5 in
Chengde].
AB - In this study, detailed activity level of typical sector in Chengde in 2013 was
obtained through a full-coverage investigation. A comprehensive emission
inventory with country-level resolution in 2013 was developed based on guide of
atmospheric pollutant emission inventory and updated emission factors. Then, the
emission inventory within 1 km*1 km grid was generated using source-based
spastial surrogates including population, road network and landuse date.
Furthemore, meteorology-air quality modeling system (WRF-CMAx) including
Particulate Source Apportionment Technology (PSAT) module was established in
order to evaluate the impact of topical sector (e. g., electric power, the
production of construction materials, the metallurgical industry, etc.) on PM2.5
concentration in January, April, July and October which were considered as the
representative months of winter, spring, summer and autumn. The results showed
the total emission of SO2, NOx, TSP, PM10, PM2.5, CO, VOCs and NH3 in Chengde in
2013 was respectively 81134 t, 72556 t, 368750 t, 119974 t, 51152 t, 1281371 t,
170642 t and 81742 t. Industrial source was the main emission contributor of SO2,
NOx, CO, VOCs, accounting for 89.5%, 51.9%, 82.5% and 45.6% of total emissions,
respectively. The major emission source of NOx also included on-road and non-road
mobile source, respectively accounting for 26.7% and 10.8%. The major emission
source of TSP, PM10 and PM2.5 was fugitive dust, accounting for 76.7%, 65.6% and
46.54%, respectively. Ammonia emissions from animals and farm accounted for 67.1%
and 15.8% of total emissions, respectively. The numerical simulation result
showed that the fugitive dust, the others, the metallurgical industry and boilers
industry had relatively higher contributions to PM2.5 concentration, accounting
for 23.1%, 20.6%, 13.3% and 11.2%, respectively. These emission sources should be
paid more attention during the decision-making with respect to control
strategies.
PMID- 29964655
TI - [Pollution Characteristics and Emission Coefficient of Volatile Organic Compounds
from Woodwork-making Industry in Zhejiang Province].
AB - To explore the pollution characteristics and emission coefficient of volatile
organic compound (VOCs) released from the woodwork-making industry in Zhejiang
province, this paper used the survey data of 310 woodwork enterprises obtained in
2015 to analyze the current VOCs treatment status of woodwork-making industry,
and further screened 213 key enterprises to study the emission coefficient of
woodwork-making industry. The results showed that more than 94% of woodwork
enterprises failed to effectively dispose VOCs since most woodwork enterprises
did not have treatment facilities. Moreover, solvent-based materials such as
adhesive and paint were still commonly used in woodwork-making industry.
Meanwhile, the main pollutants of VOCs in woodwork-making industry were dimethyl
benzene, butyl acetate, ethyl acetate, toluene and formaldehyde. Furthermore, the
VOCs emission coefficient of woodwork-making industry in Zhejiang was 93.4
g.(million Yuan)-1, while it was affected by the production processes, and the
VOCs emission coefficient of enterprises using the coating techniques was higher
than that using the adhesive techniques, being 93.6 g.(million Yuan)-1 and 9.5
g.(million Yuan)-1, respectively. Furthermore, the major polluting stage of
woodwork-making industry was coating stage, and the VOCs emission coefficient was
31.0 g.(million Yuan)-1 when waterborne and UV coating was used. The highest VOCs
emission coefficient was from wooden furniture manufacturers, which could reach
168.5 g.(million Yuan)-1 when solvent-based coatings were used.
PMID- 29964656
TI - [Emission Inventory of Anthropogenic VOCs and Its Contribution to Ozone Formation
in Shanxi Province].
AB - Based on the activity levels, emission factors and composition characteristics of
VOCs, which was obtained in statistic data and references, the emission amount of
anthropogenic VOCs in Shanxi province in 2013 was calculated, and the ozone
formation potential of VOCs was studied in this study. The results showed that
the emission amount of anthropogenic VOCs in Shanxi province in 2013 was 723700
t, with the major sector of the industrial emission and vehicle emission,
accounting for 36.47% and 24.28% of total emission amount, respectively. Coke and
chemicals production, the major emission source of VOCs in industrial emission,
emitting 190600 t and 38800 t VOCs in 2013, accounting for 72.22% and 14.72% of
industrial emission, respectively. The emission amount of ozone precursor VOCs
was 435900 t, and the total amount of ozone formation potential in Shanxi
province in 2013 was 1769900 t. The sources of the greatest contribution to total
ozone were vehicle emission, combustion sources and industrial emission. The
results indicated that industrial emission was the major source of VOCs emission,
which showed the simplification and heavy industrial structure. The increasing
numbers of vehicles led to the huge emission of VOCs in recent years. In
conclusion, the main measure of controlling the ozone pollution caused by VOCs
emissions was controlling the VOCs emission from industrial emission and vehicle
emission.
PMID- 29964657
TI - [Characteristics and Source Apportionment of VOCs of High Pollution Process at
Chemical Industrial Area in Winter of China].
AB - Online GC was adopted to monitor VOCs of high pollution process near a chemical
industrial area in winter. PMF model was used to identify the major sources of
VOCs and evaluate their contributions. The result showed that the main components
during the period of observation were toluene, xylene, C3-C4 hydrocarbon and
chloroform, etc. Organic sulfur compounds were the major odor pollutants at the
chemical industrial area. The compounds including isobutane, n-butane, propane
and acrylonitrile were enriched during two pollution periods. VOCs and NOx had
the diurnal features of high concentration in the evening versus lower
concentration during daytime, indicating the main influence from chemical
industrial sources. While O3 had the diurnal features reflecting the
photochemical reaction at chemical industrial area in winter. The PMF result
showed that 48.0% of the total VOCs concentrations were attributed to synthetic
materials industry, 24.0% to industrial organic sulfur process and wastewater
treatment (including three sources), 14.7% to industrial organic solvent usage,
and 13.3% to petrochemical process. So the wastewater treatment unit was a major
source of odor pollution at chemical industrial area.
PMID- 29964658
TI - [Study and Application of Test Method for VOCs Emission Factor of Refueling in
Service Station].
AB - VOCs emission of service station is one of the main sources of VOCs in Beijing.
Uncontrolled emission factor (UEF) of refueling in China, US EPA, EEA
respectively is 2.16, 1.31 and 1.00 times of CARB UEF (1008 mg.L-1). China's
gasoline standards have changed in the last 20 years, and there is an urgent need
to carry out the localization of gasoline refueling VOCs emission factor
research. This paper compared test methods for refueling emission factors of
European Union (EU) and California Air Resources Board (CARB) and found that the
EU method was simpler and easier to operate than the CARB method, so we processed
refueling VOCs emission factors test device in reference to EU test methods and
chose a set of United States Stage II vapor recovery system in Beijing service
stations to carry out studies on VOCs emission factors. The results showed that:
1 For the fuel test tank, refueling vapor recovery efficiencies were 0.93 and
0.83 times of air to liquid volume ratio (A/L) of Stage II respectively in winter
and summer. Refueling emission factor in summer was greater than that in winter,
and its recovery efficiency was lower than that in winter. 2 For the social
vehicles, winter and summer refueling UEF respectively was (525+/-42) mg.L-1 and
(963+/-174) mg.L-1, at the same time was 0.52 and 0.95 times of CARB refueling
UEF (1008 mg.L-1) in A/L=0.The average value of emission factors respectively was
(55+/-30) mg.L-1 and (112+/-108) mg.L-1 in A/L 1.05-1.07 in winter and summer.
3Refueling UEF without vapor recovery of social vehicles was chosen as the
localized summer and winter refueling UEF in Beijing, we could calculate the
emission factor of vapor recovery in different A/L combining with the linear
equation of the fuel test tank.
PMID- 29964659
TI - [NH3 Emission Characteristics in Landfill Sites in Beijing].
AB - NH3 is one of the main odors produced from landfill sites. It is also an
important precursor of PM2.5. According to the NH3 of ambient air and non
organizational waste gas monitoring method, the research studied NH3 emission
characteristics of two landfill sites in Beijing. The results showed that the NH3
concentrations in waste pit, sludge treatment workshop and leachate equalization
basin were 0.078-0.341mg.m-3. The NH3 concentration of key processes was rising
in daytime and decreasing in night. Temperature and relative humidity were main
meteorological influencing factors, and NH3 concentration was low in rainy
weather. The NH3 concentration declined significantly along downwind directions,
by 60.00% at 100m out of boundary and 69.90% at 300 m. This reasearch provides
scientific support for further study on localization of NH3 emission
characteristics and NH3 emission monitoring management.
PMID- 29964660
TI - [Inventory and Characteristics of Anthropogenic Ammonia Emission in Xi'an].
AB - Based on the activity data of diverse ammonia sources, the rational estimation
method and emission factors were employed, and an anthropogenic ammonia emission
inventory was further established to describe the situation of Xi'an in 2013.The
results showed that the total anthropogenic ammonia emission reached 47.17*103 t
in 2013 with an emission intensity of 4.57 t.km-2; The livestock breeding and
nitrogen fertilizers were the major sources of anthropogenic ammonia emission,
which were 20.55*103 t and 17.51*103 t, respectively, accounting for 80.68% in
total; Cow and hog were the major sources, and occupied 75.03% in livestock
breeding emission; Lintong District was the heaviest emission area, the total
emission was 10.73*103 t, which accounted for 23.22%; The emission intensity of
Yanliang District reached 14.75 t.km-2 which was considered as the most severe
area.
PMID- 29964661
TI - [Pollution Characteristics of Non-methane Hydrocarbons During Winter and Summer
in Foshan City].
AB - Thirty non-methane hydrocarbons(NMHCs) samples were collected and analyzed in
Foshan City during winter 2014 and summer 2015. The concentrations of NMHCs
during the sampling period were 122.30 MUg.m-3 and 56.22 MUg.m-3 in winter and
summer, respectively. The five highest concentration species of NMHCs in winter
and summer were in the following order: toluene (25.12 MUg.m-3), m/p-xylene
(13.76 MUg.m-3), propane (9.17 MUg.m-3), ethylbenzene (7.25 MUg.m-3), ethylene
(6.77 MUg.m-3) and toluene (6.18 MUg.m-3), m/p-xylene (5.21 MUg.m-3), o-xylene
(4.15 MUg.m-3), beta-pinene(3.75 MUg.m-3), propane (3.29 MUg.m-3). Compared to
2008, the concentrations of NMHCs have dropped significantly. The proportions of
aromatics, alkanes, alkenes and alkynes in NMHCs were 51.20%, 34.70%, 10.04%,
4.05% and 43.93%, 33.99%, 19.20%, 2.88% during winter and summer, respectively.
The ratios of NMHCs/NOx were 0.90 and 1.88, indicating that the peak ozone
concentrations in Foshan City were controlled by NMHCs during the sampling
period, and the emissions of NMHCs should be further strengthened. The propylene
equivalent concentration and ozone formation potential were 45.09 MUg.m-3 and
40.64 MUg.m-3, 392.77 MUg.m-3 and 207.77 MUg.m-3 in winter and summer. The m/p
xylene; toluene and m/p-xylene; isoprene had a very important influence on ozone
formation potential. The ratios of Benzene/Toluene were 0.15 and 0.20 indicated
that industrial process was the main source of NMHCs in Foshan City. Relative to
2008, isopentane didn't belong to the highest concentration of five pollutants
for Foshan's NMHCs in this research, indicating the measures to prevent volatile
gasoline impact on the environmental quality have achieved remarkable results.
PMID- 29964662
TI - [Water-soluble Inorganic Ions in the Road Ambient Atmospheric Particles of
Tianjin].
AB - Atmospheric particles, especially water-soluble inorganic ions are hazardous to
human body. Motor vehicle exhaust is the greatest contributor to atmosphere
pollution in Tianjin. In order to explore the emission characteristics of
different road types, PM2.5 and PM10 from four types of roads were sampled and
analyzed by water-soluble ions component analysis and Pearson correlation
analysis during the period of April to May, 2015 to discover the ratio of PM2.5
to PM10 and the major pollutants. The results showed that water-soluble inorganic
ions mainly existed in fine particles varying with different road types, which
mainly came from secondary pollution. The quantities of secondary ions in PM2.5
were twice as high as that in PM10, which were the key components of the water
soluble inorganic ions. This was probably due to the increase of automobiles and
their emissions, as well as the transmission and spreading of pollutants in the
surroundings. Furthermore, water-soluble inorganic ions might exist in the forms
of NaNO3, NH4Cl, NH4NO3, (NH4)2SO4, KCl, KNO3, K2SO4, MgCl2, CaCl2, etc. K+,
Mg2+, Na+and Ca2+ showed high homology and the contributors of PM2.5 and PM10
were mainly the mixture of combustion and secondary pollutants, then followed by
the mixture of re-suspended dust and traffic source.
PMID- 29964663
TI - [Characteristics of Nitrogen Deposition in Daiyun Mountain National Nature
Reserve].
AB - G78 nitrogen deposition collector was used to investigate the background value of
local nitrogen deposition flux in Daiyun Mountain National Nature Reserve of
Fujian province. The results showed that dry and wet nitrogen deposition of
Daiyun Mountain National Nature Reserve was 2.30 kg.hm-2 and 14.79 kg.hm-2 from
March to October in 2015. 53% of dry deposition was in the form of dissolved
organic nitrogen (DON, 1.21 kg.hm-2). The main form of inorganic nitrogen (DIN)
in dry deposition was NO3- deposition (0.71 kg.hm-2), with NH4+ deposition (0.37
kg.hm-2) being lower compared to NO3- deposition. DON and DIN flux in wet
deposition was 5.38 kg.hm-2 and 9.41 kg.hm-2, respectively. DIN flux in wet
deposition was mainly in the form of NH4+ deposition (6.07 kg.hm-2). Wet nitrogen
deposition flux was found positively correlated with local precipitation. Wet
nitrogen deposition in Daiyun Mountain National Nature Reserve might have
significant negative effects on local water resource.
PMID- 29964664
TI - [Microbial Activity in Bioaerosols in Winter at the Coastal Region of Qingdao].
AB - In order to study the level and size distribution of microbial activity of
atmospheric bioaerosols, bioaerosol samples were collected from November 2015 to
January 2016 using size-fractionated bioaerosol samplers at the coastal region of
Qingdao, and the microbial activity was measured using the fluorescein diacetate
(FDA) hydrolysis method. The results showed that the level of microbial activity
was in the range of 21.89-108.59 ng.m-3 sodium fluorescein during the sampling
period, with an average of 59.43 ng.m-3 sodium fluorescein in Qingdao. Size
distribution of microbial activity exhibited a tendency, the activity increased
with increasing particle size. The microbial activity on particles with coarse
size (>2.1 MUm) was higher than that on fine size, with the highest average
proportion of 24.06% for coarse size larger than 7.0 MUm. The daily variation of
microbial activity was different for different samples, which showed no
significant diurnal variation in winter. The correlation analysis showed that
microbial activity was significantly correlated with wind velocity(r=0.445, n=33,
**P<0.01) during the sampling period. However, microbial activity showed no
significant correlation with the meteorological factors, such as
temperature,relative humidity and UV intensity during the sampling period.
Moreover, there was no significant correlation of microbial activity with air
quality factors, such as AQI, PM2.5, PM10, CO, NO2, O3 and SO2. Source of air
mass had significant impact on microbial activity. The average level of microbial
activity was 100.33 ng.m-3 sodium fluorescein on sunny days, and the level
decreased to 56.53 ng.m-3 sodium fluorescein on hazy days. When the haze was
mixed with fog and this special circumstance lasted for several days, the
microbial activity reduced to 37.7% of the level of sunny days. Therefore,
consecutive hazy weather had great influence on microbial activity.
PMID- 29964665
TI - [Molecular and Carbon Isotopic Compositions of n-Alkanoic Acids in Smoke from
Maize Straw Combustion].
AB - Four cultivars of maize straw were burned under flaming and smoldering
conditions. Smoke samples were colleted and analyzed by GC/MS and GC/C/IRMS to
determine molecular and stable carbon isotopic compositions of n-alkanoic acids
in them. The results showed that n-alkanoic acids in flaming smoke were composed
of C7 to C34, with a mean total content of 13895.0 mg.kg-1. The average ratio
values of the content for homologues with lower carbon number (<=C16) to that for
ones with higher carbon number (>C16) (L/H), C18/C16, C24/C16, C24/C18, and
C24/(C22+C26) (CAR) were 1.1, 0.33, 0.17, 0.50, and 1.2, respectively. Moreover,
the acids exhibited a bimodal profile with peaks at C16 and C24, respectively.
They had evident even to odd carbon number predominance (mean CPI: 4.5). In
smoldering smoke the acids were consisted of C6 to C34, with an average total
content of 50183.7 mg.kg-1. The mean ratios of L/H, C18/C16, C24/C16, C24/C18,
and CAR were 1.3, 0.33, 0.20, 0.60, and 1.6, respectively. In addition, the
homologues had the same distribution pattern as in flaming smoke and even to odd
carbon number predominance (mean CPI=6.1). The mean carbon isotopic ratio
(delta13 C) values for individual n-alkanoic acids (C14 to C26) in flaming smoke
ranged from -21.00/00 to -24.80/00, the overall average of which was -23.50/00.
The difference between mean delta13 C values of n-fatty acids in flaming smoke
and the straw (Delta13 C) was -0.70/00. In smoldering smoke, the mean delta13 C
values for the compounds varied from -21.80/00 to -25.40/00, with an overall
average of -23.30/00. The Delta13 C value was up to -0.50/00. The molecular and
carbon isotopic compositions of n-alkanoic acids in smoke were significantly
different from those in straw matter. L/H, C24/C16, C24/C18, CAR, and delta13 C
might be useful proxies to discriminate the organic pollutants in atmospheric
aerosols derived from maize straw combustion.
PMID- 29964666
TI - [Gas Transfer Velocity of CH4 at Extremely Low Wind Speeds].
AB - Thin boundary theory equation (TBL) is widely used to determine gas fluxes across
water-air interfaces, and the gas transfer velocity (k600) is the key
environmental factor in the equation. A monthly field campaign was carried out
during one year to measure CH4 flux and to probe its exchange rate across the air
water interface in a drinking reservoir and 5 adjacent ponds. The ranges of wind
speed and surface water temperature were 0-0.75 m.s-1 and 6.3-30.9Crespectively,
and their average values were 0.19 m.s-1 and 19.3C respectively. The gas transfer
velocity of CH4 varied from 0.20 to 1.99 cm.h-1 with an average of 0.50 cm.h-1.
Correlation functions between the gas transfer velocity and the wind speed at 10
m height (U10) and surface water temperature (Tw) were given here to quantify
k600. There were significant correlations between the fitted values and actual
values both for original and bin-averaged data.
PMID- 29964667
TI - [Spectral Characteristics of Chromophoric Dissolved Organic Matter (DOM) from a
Typical Reservoir Lake from Inland of Three Gorges Reservoir Areas: In the View
of Riparian Ecosystem Analysis].
AB - For further understanding the geochemical characteristics of dissolved organic
matter (DOM) in "reservoir-type" lake, in this study a typical "reservoir-type"
lake, Changshou Lake located in inlands of Three Gorges Reservoir areas, was
selected to investigate the composition, sources and spatial distributions of
chromophoric DOM (CDOM) in this lake, through UV-Vis and three-dimensional
fluorescence spectroscopy combined within analysis of riparian eco-system
differences. The results showed that DOM concentrations including dissolved
organic carbon (DOC) and CDOM abundance in different sampling sites varied
spatially to a certain degree, in contrast to fluorescence component of DOM
showing a constant level. In backwater zone (also called stagnant zone
alternatively), due to accumulation of DOM and limited impact of terrestrial
contribution, the endogenesis (autochthonous production) was the predominant
geochemical process showing an obvious "authigenic-control" characteristic, and
relatively lower aromaticity and molecular weight. In comparison, sampling sites
surrounding artificial forests and tourism development, the highly humic (highly
aromatic) substances resulted from terrestrial inputs were the main source, but
discharge due to human activities was also responsible for highly protein-like
component observed in DOM. Additionally, in the entry zones of lake from upstream
river, DOM was affected by fruit plantations and residences, contribution from
upstream river could also be neglected. From the other aspects, some significant
correlations were also observed, which were independent of riparian eco-system
differences, for example, the SUVA280 versus S(275-295) (negative), CDOM versus
FDOM (positive), and CDOM and S(275-295) (negative), indicating the correlation
was an intrinsic property of DOM that could not be affected by the surrounding
environment. Meanwhile, the main chromophoric component of CDOM in Changshou Lake
was high molecular weight (HMW) components within highly aromatic structures. At
least, 51% of CDOM dynamic could be explained by changes of FDOM, especially in
backwater zone the co-variance was more obvious. Furthermore, when the
traditional fluorescence index (FI) could not comprehensively explain the
differences of DOM sources due to very similar (statistically insignificant)
values, integration of UV-Vis and fluorescence spectral characteristics and
detailed discussion of riparian eco-system differences, might be an important way
to help further resolution of DOM composition and sources in aquatic
environments, such as lake, river and watershed.
PMID- 29964668
TI - [Characteristics and Pollution Source Analysis of Nutrients in Tributary Outlets
of Xitiaoxi Watershed].
AB - The input of tributary is the important source of nutrients to the main stream,
and it is the key area for water pollution control of watershed. In order to
explore the sources of nutrient and seek the effective measures to control the
river pollution, the spatial and temporal variations of aquatic parameters and
the output of nutrient flux in the tributary outlets of Xitiaoxi watershed were
analyzed. The quantitative analysis concerning the contribution of pollution
sources from 10 typical tributaries was carried out, using the PMF analytical
model. The results showed that the TN and TP concentrations were higher in the
middle and lower reaches. In the temporal scale, the concentrations of nutrients
in the dry season were higher than those in the wet season. In the dry season,
average concentrations of TN and TP were 4.25 mg.L-1 and 0.11 mg.L-1,
respectively, compared to the corresponding values of 3.15 mg.L-1 and 0.09 mg.L-1
in wet season. Because of the differences of surrounding lands, the sources of
nitrogen and phosphorus forms were various. The results of PMF(Positive Matrix
Factorization) method identified the three nutrient sources as agricultural
source, aquaculture source and municipal source. In different seasons and river
reaches, the contribution rates of three sources were different. Agricultural
source contributed nutrient largely to the tributaries in the upstream reaches,
and the aquaculture source was the main contributor in the middle reaches, while
the municipal source contributed more nutrient in the wet season than in the dry
season. Therefore, to better improve water quality of Xitiaoxi watershed, the
surrounding environment of tributary and the characteristics of nutrients in
spatial and temporal variations should be considered.
PMID- 29964669
TI - [Analysis of Driving Factors on the Nitrogen Decrease in the Early Stage of the
Thermal Stratification in Main Area of Zhoucun Reservoir].
AB - In order to explore the trend and driving factors of nitrogen in the early stage
of the thermal stratification in Zhoucun reservoir, the water quality indicators
in main reservoir area of Zhoucun reservoir were monitored regularly form
February to April (2016). Meanwhile, the fresh water and surface sediments in the
sampling point were collected to study the effect of water and sediment
denitrification by simulation in laboratory. The results showed that: the
concentration of TN decreased from (2.28+/-0.09) mg.L-1 to (1.08+/-0.09) mg.L-1,
the concentration of nitrate nitrogen decreased from (1.66+/-0.09) mg.L-1 to
(0.25+/-0.06) mg.L-1, whereas the concentration of ammonia nitrogen and nitrite
showed little change in the early thermal stratification of Zhoucun reservoir. At
the same time, chlorophyll was not significantly increased, so the algae had
little effect on nitrogen; the decreasing nitrogen was mainly due to the aerobic
denitrification. Gradually increased temperature,the changes of DO and pH and the
composition of organic matter (low molecular weight) were beneficial to the
growth of aerobic denitrifying bacteria. Furthermore, the number of bacteria
increased from 1.06*105 cfu.L-1 to 8.33*106 cfu.L-1, which enhanced the
denitrification of the reservoir; Meanwhile, in the simulation experiments, the
TN removal rates of water and water-sediment systems reached 0.7 mg and 3.3 mg,
respectively. Water and sediment denitrification ratio was generally 1:4, and the
aerobic denitrification of surface sediment was an important factor in the
removal of nitrogen in reservoir.
PMID- 29964671
TI - [Impacts of Multiple Disturbance on Migration and Transformation of Endogenous
Phosphorus in Lake].
AB - This work aimed to clarify the influence of multiple disturbance factors on the
migration and transformation of endogenous phosphorus. In this experiment, the
sediment of Meiliang Bay in Taihu Lake was studied as the major research object.
With the help of Rhizon sampling technique, Unisense microelectrode system and so
on, this experiment studied the change regularities of dissolved oxygen between
sediment and water interface, different forms of phosphorus and iron ions under
disturbance. The results indicated that the dissolved oxygen content in sediment
decreased in the presence of Corbicula fluminea as compared with the control
experiment. Disturbance made the peak area of DIP in interstitial water to
migrate from 3-4 cm to 4-5 cm, which suggested that the "active region" of DIP
regeneration went deeply into sediment with the appearance of Chironomus plumosus
and Corbicula fluminea. Meanwhile, the existence of Corbicula fluminea and algae
further reduced DIP in the interstitial water. That was because the released
NH4Cl-P was transferred to phosphorus in overlying water and Fe/Al-P. With the
increase of disturbance factors, the transformation ratio from NH4Cl-P to Fe/Al-P
also increased gradually (from 44% to 59%).
PMID- 29964670
TI - [Characteristics of Organic Phosphorus Fractions in the Sediments of the Black
Water Aggregation in Lake Taihu].
AB - Potential release of phosphorus in lake sediments depends largely on the
fractions and distribution of organic phosphorus. MaoDu was chosen as the
research area in the west of Lake Taihu. The chemical forms of the surface
sediments were investigated by the Ivannoff extraction methods. The results
showed that the main organic phosphorus form of sediments at different sampling
places was humic acid-OP. It accounted for 35% of the total organic phosphorus.
Horizontal distribution: Total organic phosphorus content from the shore to the
middle of total showed a trend of rising after decline; vertical distribution:
Total organic phosphorus content was the lowest in 2-6 cm and the highest in 4-8
cm. Various phosphorus content followed the order of humic acid-OP > residual-OP
> HCl-OP > fulvic acid-OP; the relative content of NaHCO3-OP in the total organic
phosphorus content showed a trend of rising followed by reduction and then rising
again from the shore to the middle, cyanobacteria residue deposition increased
the content of NaHCO3-OP in sediment. Contents of NaHCO3-OP and humic acid-OP
both first reduced, then increased and finally reduced in the vertical
distribution, the content of NaHCO3-OP was the lowest in 4-6 cm and humic acid-OP
was the highest in 4-8 cm. HCl-OP and fulvic-OP decreased with increasing depth
in the vertical distribution. The content of residual-OP showed stable tendency
in the vertical direction and was about 45 MUg.g-1. Labile OP and pH, DO, the
depth of water were significantly negatively correlated, OM and NaOH-Pi were
significantly correlated with total organic phosphorus, labile OP, moderately
labile OP and nonlabile OP. Three components of organic phosphorus had bio
availability and played an important role in lake eutrophication. The increase of
the content of labile OP might promote the black water aggregation (BWA) in
cyanobacteria accumulation.
PMID- 29964672
TI - [Change of Soil Nitrogen Leaching with Summer Maize Growing Periods Under Plastic
Film Mulched Cultivation in Danjiangkou Reservoir Area, China].
AB - As an important form of agricultural non-point source pollution, soil nitrogen
leaching deteriorates water quality. Compared with non-mulching cultivated land,
field experiment explored the change characteristics of soil nitrogen leaching
under plastic film mulching ridge-furrow in Wulongchi small watershed during
summer maize growing period. The results showed that the amounts of mulching
tillage soil TN and NO3--N leaching were significantly lower than those with non
mulched treatment, by 25.68% and 20.25%, respectively. With the advance of the
summer maize growth period, leaching amount of mulched soil TN was highest at
seedling stage, lowest at heading stage and higher in maturation period; leaching
amount of mulched soil NO3--N was highest at seedling stage, lowest in maturation
period; leaching amount of mulched soil NH4+-N was lower at seedling stage,
increased to the peak at the jointing stage, decreased to the valley value at
heading stage, and obviously increased in maturation period. Linear function
relationship was found between mulched soil TN leaching and TN content, while
exponential relationship was found between mulched soil NO3--N leaching and NO3-
N content. In addition, there was linear function relationship of mulched soil TN
and NO3--N leaching amount with soil moisture and rainfall. It was concluded that
the plastic film mulched on summer maize could reduce the leaching loss of soil
nitrogen, and it would have a significant effect on the reduction of reservoir
area of agricultural non-point source pollution.
PMID- 29964673
TI - [Nutrients Recovery on the Growth of Nitrogen and Phosphorus Starved Microcystis
aeruginosa].
AB - Microcystis in natural water bodies may frequently go through periods of nutrient
limitation and then may recover when the limited nutrient becomes available. We
investigated changes in cell physiology and expression of photosynthesis-related
genes during the recovery of Microcystis aeruginosa from nitrogen starvation and
phosphorus starvation with the method of 14C isotope and fluorescent quantitative
PCR. Our results suggested that Microcystis cells relieved from N starvation and
P starvation resumed growth within 24 h and displayed significantly higher growth
rates than not-starved-cells in the first 48 h. Carbon production rates and the
expression levels of photosynthesis-related genes all increased rapidly after
relieving from N starvation and P starvation in different degrees, enabling the
rapid recovery from nutrient starvation. However, N-starved cells can not resume
their cellular activity to full capacity when N became available and the damage
of N deficiency to M. aeruginosa was unrecoverable, whereas cellular activity of
P-starved cells could recover to normal properties.
PMID- 29964674
TI - [Inactivation Efficiency and Mechanism of Three Dominant Fungal Spores in
Drinking Groundwater by Chlorine].
AB - The outbreak of fungi in drinking groundwater sources can produce odor, cause
toxicity and form lots of visible flocs, which seriously affect the drinking
water quality. In this study, the inactivation efficiency of three dominant
fungal spores Trichoderma, Penicillium, Cladosporium by chlorine was conducted,
and the inactivation mechanism was explored by monitoring the hydrophobicity, the
leakage of intracellular substances, the increase of extracellular adenosine
triphosphate (ATP), deoxyribonucleic acid (DNA) and proteins, and the change of
spores' morphology. The results showed that the inactivation of fungal spores was
consistent with first-order kinetics and satisfied the Chick model. The
resistance to chlorine was in sequence of Trichoderma > Penicillium >
Cladosporium, the larger size the fungal spores and the more hydrophilicity the
fungal spores, the higher the inactivation efficiency. Chlorination resulted in
the remarkable leakage of intracellular compounds, the increase of extracellular
characteristic compounds (ATP, DNA and protein), the damage of the cell surface,
and the fungal spores recessed and wrinkled. In summary, chlorine firstly reacted
with spores' surface and reduced their cultivability, and then resulted in the
damage to the permeability barrier of the spores and the release of intracellular
characteristic compounds, and finally the viability of spores was damaged.
PMID- 29964675
TI - [Effect of Water Treatment Process on the Bacterial Multidrug Resistance in
Drinking Water].
AB - The overuse of antibiotics has resulted in contamination of antibiotics and genes
encoding multidrug resistance in some water sources in China. Antibiotics and the
antibiotic resistance genes may cause severe hazards to human health via drinking
water. Cultivable bacteria in one of the water supply systems in Shanghai were
isolated and identified. The multidrug resistance in drinking water for
cultivable bacteria and their change and mechanism in water supply system was
analyzed using ampicillin (Amp), kanamycin (Kan), rifampicin (Rif),
chloramphenicol (Cm) and streptomycin (Str). The results showed that, the
isolated microorganisms mainly belonged to 16 genera. Bacillus sp., Arcicella
rosea sp. and Sphingomonas sp. existed in the whole process. The multidrug
resistances of these three bacteria were enhanced after flowing carbon filtration
and water distribution system. Bacillus sp. showed the strongest antibiotic
resistance. Real-time PCR was used to quantitatively evaluate the concentration
of three integrons and 9 transposons in the water supply system. The results
showed that, after BAC filtration and water distribution system, the absolute
concentrations of mobile genetic elements increased obviously, which meant that
BAC filtration and water distribution system played an important role in
influencing antibiotic resistance in the water treatment process.
PMID- 29964676
TI - [Characteristics of Disinfection By-products and Genotoxicity During Drinking
Water Disinfection with Potassium Monopersulfate Compound Powder].
AB - The qualitative analysis for by-products in the course of disinfection of the raw
water and the effluent of GAC in Beijing Tiancuishan Drinking Water Treamtment
Plant by potassium monopersulfate compound powder was determined. Halogen
disinfection by-products during disinfection process by potassium monopersulfate
compound powder was evaluated in a bench scale by comparing with chlorine
disinfection process, and the genotoxicity evaluation of potassium monopersulfate
compound powder and chlorine disinfection processes was also conducted by umu
test. The results showed that there were small changes in the organic pollutant
components of water samples after disinfection by potassium monopersulfate
compound powder, while some new halogen disinfection by-products were generated.
Disinfection with potassium monopersulfate compound powder generated much less
trihalomethanes (THMs) and haloacetic acids (HAAs) than chlorination
disinfection. Moreover, the results of umu test indicated that the raw water and
the effluent of GAC presented lower genotoxicity after potassium monopersulfate
compound powder disinfection than chlorine disinfection. However, there was a
risk for safety at a high level of organic matters and disinfectant dosage during
potassium monopersulfate compound powder disinfection process.
PMID- 29964677
TI - [Heterogeneous Activation of Peroxymonosulfate with Three-dimensional Ordered
Mesoporous Co3O4 for the Degradation of Rhodamine B].
AB - Three-dimensional ordered mesoporous Co3O4 was prepared by nanocasting method
with porous silicon KIT-6 as the hard template and firstly used to activate
peroxymonosulfate for the degradation of rhodamine B. The structural properties
were characterized by BET, H-TEM, XRD, XPS, FT-IR. The results showed that three
dimensional ordered mesoporous Co3O4 presented far superior catalytic activity
over conventional nanoscale Co3O4 due to its abundant space mesoporous channel
structure and the large specific surface areas. Higher catalyst dosage and higher
peroxymonosulfate concentration favored the decolorization of rhodamine B. The
removal of rhodamine B could be accelerated in the presence of Cl- and H2PO4-;
however, the decolorization of rhodamine B would be inhibited in the presence of
NO3-, SO42- and HCO3-. Sulfate radicals were identified as the dominant active
species for the decolorization of rhodamine B through radicals quenching
experiments. Three-dimensional ordered mesoporous Co3O4 showed excellent
catalytic activity even after five consecutive cycles.
PMID- 29964678
TI - [Enhanced Mitigation of Membrane Fouling by Regulations on Floc Morphology in
Electrocoagulation].
AB - In this study, the electro chemical parameters were regulated to control the floc
morphology in order to mitigate membrane fouling. The main effects of current
density, initial pH and conductivity on the floc characteristics and flux were
studied, and the mechanisms of interaction between flocs with different
morphology structures and ultrafiltration membranes were analyzed. The results
showed that the key to mitigate the membrane fouling by electrocoagulation was to
form a loose and porous cake layer on the membrane surface. The
electrocoagulation-ultrafiltration (EC-UF) technology could not only effectively
mitigate the membrane fouling, but also greatly enhance the water quality of the
effluent. By increasing the current density and keeping water quality conditions
at neutral pH, the EC-UF technology could maintain a higher flux. Under
conditions of j=20 A.m-2, initial pH=7 and initial conductivity=1000 MUS.cm-1,
the removal rate of humic acid (HA) was 97%, and the normalized specific flux of
J/J0 was 81%.
PMID- 29964679
TI - [Effect of Initial pH on Nitrogen Removal Performance and N2O Emission of a
Sequencing Batch CANON Reactor].
AB - A completely autotrophic nitrogen removal over nitrite (CANON) reactor with
haydite as carrier was operated in a sequencing batch biofilm reactor. The effect
of different initial pH on nitrogen removal performance and N2O emission was
investigated using synthetic inorganic ammonia-rich wastewater as influent at
30C+/-1C. During the experiment, the pH of influent was controlled at 6.64, 6.98,
7.15, 7.88 and 7.95 under the same influent ammonia concentration condition, with
hydraulic retention time of 5 hours and aeration rate of 6 m3.(m3.h)-1. The
results showed that, when the initial pH was between 6.64 and 7.95, the
performance of autotrophic nitrogen removal over nitrite was basically stable.
The total nitrogen removal efficiencies were 81.38%, 87.32%, 92.12%, 88.21% and
86.84%, respectively. And the total nitrogen removal loads were all higher than
1.56 kg.(m3.d)-1. Initial N2O emission rates were basically equal and decreased
after rising to a peak value. Besides, the lower the initial pH was, the higher
the maximum N2O emission rate was. In addition, N2O emissions and ratios
decreased with rising initial pH. Initial pH between 6.64 and 7.95 had little
influence on nitrogen removal but N2O emissions. Initial pH should be kept at
about 7.90 to achieve high efficient nitrogen removal and reduction of N2O
emission synchronously.
PMID- 29964680
TI - [Operational Characteristics of the Simultaneous Nitrogen and Phosphorus Removal
and Removal of Phthalate Esters by Three-dimensional Biofilm-electrode Coupled
with Iron/Sulfur Reactor].
AB - In order to explore the technological characteristics of the simultaneous removal
of phthalate esters (PAEs) as well as nitrogen and phosphorus by the novel
technology of three-dimensional biofilm-electrode coupled with iron/sulfur
reactor (3DBER-S-Fe), the changes of the total nitrogen (TN),total phosphorus
(TP),DBP,DEHP,NO3--N, SO42- and pH value were analyzed under the hydraulic
retention time (HRT) of 8 h, 6 h and 4 h respectively. The results showed that
3DBER-S-Fe could remove nitrogen, phosphorus and PAEs effectively. Under the HRT
of 8 h, 6 h and 4 h, the removal rates of TN were 80.99%, 78.85% and 64.76%; TP
were 65.18%, 67.17% and 43.44%; DBP were 96.72%, 97.32% and 96.53%; DEHP were
91.89%, 81.57% and 74.30%, respectively. There were heterotrophic
denitrification, hydrogen autotrophic denitrification and sulfur autotrophic
denitrification processes in the 3DBER-S-Fe, the elemental sulfur could
compensate for the relative shortage of denitrification electron donor caused by
the increase of NO3--N load in the influent as a result of maintaining a high
efficiency of the denitrification system when the HRT was shortened from 8h to
4h; the iron ions produced by the corrosion of the sponge iron filler in the
system had a sustainable and efficient function of removing phosphorus by
precipitation; the 3DBER-S-Fe process combined the interactions of physical
adsorption, biological degradation and electrochemical processes which supported
its high removal rates of DBP and DEHP under the different HRT conditions.
PMID- 29964681
TI - [Phosphorus Removal Mechanism of Sulfur/Sponge Iron Composite Fillers Based on
Denitrification].
AB - In order to improve the phosphorus removal effect in the denitrification and
phosphorus synchronous removal process by sulfur/sponge iron composite fillers,
the phosphorus removal effect by different fillers with the coupling
microorganisms was studied to analyze the denitrifying phosphorus removal
mechanism of the microbial coupling sulfur/sponge iron composite fillers. The
research result showed that the phosphorus removal ratio of sponge iron/sulfur
composite fillers was over 95%, which was increased by 30% as compared to only
sponge iron filler. In addition, the effluent TP concentration was reduced to
less than 0.1 mg.L-1. The analysis of X-ray diffraction(XRD)and total iron
concentration indicated that the main phosphorus removal system products which
were produced in the corrosion and phosphorus removal process of sponge iron were
FeOOH, FeS and Fe4 (PO4)3 (OH)3 deposits and dissolved iron ions; FeS and FeOOH
which were the hydrolysis products of Fe2+ and Fe3+ converted PO43- to
Fe4(PO4)3(OH)3 by adsorption and deposition so that phosphorus removal could be
achieved. After the reactor of microbial coupling sulfur/sponge iron carbon
composite fillers became stable, the removal efficiency of TN and TP could reach
90% and more than 83%, respectively; Corrosion of sponge iron and phosphorus
removal process could also be promoted by biological iron and H+ that was
produced in the sulfur autotrophic denitrification process, the system could
realize the combination of "heterotrophic synergy autotrophic" composite
denitrification and chemical phosphorus removal, and efficient denitrifying
denitrification synchronous phosphorus removal process could be achieved in the
urban sewage treatment plant.
PMID- 29964682
TI - [Optimization of Denitrifying Phosphorus Removal Performance Based on ABR-MBR
Combined Process].
AB - An integrated process based on combination of the anaerobic baffled reactor(ABR)
membrane bioreactor(MBR) was adopted to treat domestic sewage with low C/N ratio.
In order to realize the function of highly efficient denitrifying phosphorus
removal, nitrate recycling ratio and sludge recycle ratio were optimized in this
study. The results indicated that the optimized denitrifying phosphorus removal
efficiency was achieved under the conditions of organic loading rate of 2.0
kg.(m3.d)-1 in ABR, total hydraulic retention time (HRT) of ABR-MBR at 9 h, the
SRT at 15 d, sludge reflux ratio of 100%, and nitrate recycling ratios set to
300%. The average removal rates of TN and soluble PO43--P were 84% and 94%, the
amount of phosphorus removed by denitrifying accounted for 87% of the total
phosphorus removed, and the average effluent concentration for TN and soluble
phosphorus were 12.98 mg.L-1 and 0.43 mg.L-1 respectively.
PMID- 29964683
TI - [Effect of Moderate and Room Temperature on Nitrogen Removal in PN-ANAMMOX
Process].
AB - The effect of moderate and room temperature on nitrogen removal rate and
microbial community was studied in PN-ANAMMOX process by inoculating mature
nitrification membrane and ANAMMOX sludge. The results showed that the PN-ANAMMOX
combined process was achieved at room temperature, and the nitrogen removal rate
reached 0.5 kg.(m3.d)-1. But the activity of ANAMMOX did not reach its maximum
due to the decreased NO2--N production rate, resulting in far lower nitrogen
removal rate of PN-ANAMMOX than that at moderate temperature which reached 1.75
kg.(m3.d)-1, and the effluent had poor water quality. When the temperature rose,
the NOB grew rapidly, the PN process became unstable, but the activity of NOB
could be effectively controlled by increasing the return flow. The results of
QPCR analysis showed that the inoculation of AOB and ANAMMOX was not conducive to
the growth at room temperature, and part of the microorganisms died. When the
environment was recovered to moderate temperature, the corresponding functional
microorganisms appeared to grow rapidly. Therefore, suitable temperature should
be provided for the microorganisms during the operation of the PN-ANAMMOX
combined process.
PMID- 29964684
TI - [Influence of Biological Activated Carbon on Simultaneous Nitrification and
Denitrification in Inflow with Different C/N Ratios].
AB - Influence of biological activated carbon (BAC) on simultaneous nitrification and
denitrification (SND) in inflow with different C/N ratios was investigated with
continuous operation of BAC reactor and SBR. Methanol was added as carbon source
and the inflow C/N ratio was set to 3, 5, 8 and 10 to run for about 120 cycles,
under conditions of indoor temperature (15-27C), initial DO 2-3mg.L-1. The TN
removal efficiency and stability of two reactors were compared. The results
showed that, BAC reactor had a higher TN removal efficiency than SBR at different
C/N ratios. TN removal rate of BAC reactor was 44.88%, 58.07% and 66.64%, when
the C/N ratio was 3, 5 and 8 respectively. After increasing the C/N ratio to 10,
the BAC reactor could maintain TN removal rate of 63.65%, but the SBR showed
sludge bulking. BAC provided various DO environments for microorganisms in a
vessel, which was beneficial to SND. BAC could reduce the influence of excessive
carbon source on the nitrification system, enlarge the application range and
improve the stability of reactor at different C/N ratios, and increase the
nitrogen removal capacity of organic matter. BAC provided condition for efficient
nitrogen removal.
PMID- 29964685
TI - [Biotransformation of Nitrate to Nitrogen Gas Driven by ANAMMOX Microbes via Zero
valent Iron Under Anaerobic Conditions].
AB - A novel type of nitrate removal process was investigated in this study, which
coupled nitrate reduction by zero-valent iron(ZVI) with anaerobic ammonia
oxidation(AMAMMOX). The zero-valent iron dosage was 71 g.L-1. The inoculation
volume of ANAMMOX granular sludge was 200 mg.L-1. The agitation rate and
environment reaction temperature of the CSTR was set up to 150 r.min-1 and 33C+/
0.5C, respectively. The pH of influent was maintained at 7.0-8.0.The result
indicated that ANAMMOX bacteria could survive in nitrate and ZVI supplied system
under neutral condition. The reactor was set up quickly with the nitrogen removal
rate of 0.12 kg.(m3.d)-1 on the first 5 days, and maintained over 0.1 kg.(m3.d)-1
nitrogen removal ability with the effluent nitrite and ammonia concentrations
below 2.0 mg.L-1 and pH value higher than 8.0. The nitrogen loss was up to 89%
under the condition of 30-40C, pH 4-6.Too extreme pH and temperature conditions
were not favorable for the coupling reactions.
PMID- 29964686
TI - [A Comparative Study on Performance of an Intermittent Aeration SBR and a
Traditional SBR for Treatment of Digested Piggery Wastewater].
AB - An intermittently aerated sequencing batch reactor (IASBR) and a traditional
sequencing batch reactor (SBR) were respectively used for treating digested
piggery wastewater, and the pollutant removal performance was studied at
different ratios of chemical oxygen demand (COD) to total nitrogen (TN) in the
influent and different loading rates. The results showed that the pollutant
removal rates in the IASBR were much higher than those in the SBR. Under influent
COD/TN of about 2.2 and NH4+-N loading of (0.12+/-0.04) kg.(m3.d)-1, the removal
rates of NH4+-N, TN and TOC in the IASBR were 97.2%+/-4.4%, 81.5%+/-7.5% and
88.5%+/-2.4%, respectively, higher than the corresponding rates of 78.3%+/-19.6%,
79.8%+/-4.9% and 86.6%+/-3.2% in the SBR. As the NH4+-N loading was increased to
(0.18+/-0.02) kg.(m3.d)-1, the removal rates of NH4+-N, TN and TOC in the IASBR
were slightly decreased to 92.4%+/-7.3%, 77.5%+/-5.3% and 86.4%+/-2.2%, but still
higher than the corresponding values of 78.1%+/-15.4%, 61.8%+/-11.2% and 81.8%+/
5.6% in the SBR. As the NH4+-N loading was remained at (0.20+/-0.01) kg.(m3.d)-1,
but the influent COD/TN ratio was increased to about 3.0, the pollutant removal
rates in both IASBR and SBR were increased, compared to those at influent COD/TN
ratio of 2.2.The removal rates of NH4+-N, TN and TOC in the IASBR were 99.6%+/
0.2%, 91.5%+/-2.9% and 92.0%+/-0.9%, respectively, higher than the corresponding
rates of 90.2%+/-1.4%, 83.0%+/-1.9% and 90.2%+/-0.5% in the SBR. Based on the
above, the IASBR was more efficient in TN and ammonium removal and more shocking
load resistant, and therefore was more feasible than SBR for treating low COD/TN
ratio wastewaters such as the digested piggery wastewater.
PMID- 29964687
TI - [Biological Pre-treatment of Surplus Sludge Using the Protease-secreting
Bacteria].
AB - The performances of biological pre-treatment were compared at different
inoculation ratios of Bacillus licheniformis (0.17%, 0.66%, 1.16% and 1.65%,
TS/TS), in order to evaluate the influence on sludge liquefaction and its
dewaterability. The analysis showed that biological pre-treatment by inoculating
Bacillus licheniformis accelerated the dissolution of intracellular materials and
increased the degradation of protein, but the sludge dewaterability deteriorated.
When the inoculation ratio of Bacillus licheniformis was 1.16%, the cumulative
effect of dissolved organic carbon reached its maximum. Keeping increasing the
inoculation ratio would not result in any improvement. At an inoculation ratio of
1.16%, the quantity of protein per volatile solid reached the minimum, which was
72% of the initial value, after 129 hours of digestion, which reflected the
maximal degradation rate of protein. But at same time, the value of CST of sludge
doubled, which indicated the deterioration of sludge dewaterability.
PMID- 29964688
TI - [Transfer and Fate of Polybrominated Diphenyl Ethers in an Electrical Equipment
Dismantling Area Using a Multimedia Fugacity Model].
AB - The multimedia fugacity model (III) was used to simulate the distribution,
transfer and fate of typical polybrominated diphenyl ethers (PBDEs) in air,
water, soil and sediment in an electrical equipment dismantling area in eastern
China. The modeling data were compared with monitored values in air, soil and
sediment for validation purpose. Moreover, the transfer fluxes between different
compartments were analyzed in order to infer the main transfer process.
Parameters of the model were tested and the key parameters were identified using
sensitivity analysis method for BDE47 and BDE209.The results of sensitivity
analysis indicated that vapor pressure, the lgKow value and half-life had
significant influence on concentrations of PBDEs in different media. The results
showed that when the system reached equilibrium, most of the PBDEs would be
accumulated in soil and sediment. The air advection outflow and soil degradation
were the major routes for PBDEs to disappear in the area. The results will
provide the basis for the risk management of PBDEs contamination.
PMID- 29964689
TI - [Distribution Characteristics of Polycyclic Aromatic Hydrocarbons in
Environmental Media in Nanning City].
AB - In order to understand the contamination characteristics of polycyclic aromatic
hydrocarbons in different environmental media, the authors collected samples of
air, atmospheric dry and wet depositions, soil and groundwater in winter and
summer in Nanning, using component spectra of 16 kinds of polycyclic aromatic
hydrocarbons, combining with the physical and chemical properties, analyzed
concentration, composition and distribution characteristics of the PAHs in
different environment media, the results showed that PAHs with 2 to 3 rings were
dominant in the air and atmospheric dry and wet depositions, and ? PAHs in winter
were higher than in summer because of the seasonal differences. And PAHs with 2
to 3 rings were dominant in soil, too. Distribution difference of soil particle
diameter was the main reason for the PAHs distribution characteristics in
different horizons. And species of PAHs in groundwater were fewer, with lower
concentrations, which showed that soil vadose zone could entrap more PAHs. The
mass fraction of 16 kinds of polycyclic aromatic hydrocarbons in different
environmental media presented a decreasing trend from low rings to high rings,
and the distribution characteristics of PAHs with 2 to 3 rings and 5 to 6 rings
in different environmental media in two areas in winter and summer had good
consistency, but also had certain differences because of the physical and
chemical properties of PAHs, hydro-geological conditions, urban pollution,
weather conditions, etc.
PMID- 29964690
TI - [PBDEs Levels in House Dust and Human Exposure to PBDEs via Dust Ingestion in
Hangzhou].
AB - In order to evaluate the pollution degree of the dust in Hangzhou City, the
indoor dust samples of 19 offices, families and students' dormitories were
collected from August to March in 2013 at Hangzhou for evaluating the pollution
level of polybrominated diphenyl ethers (PBDEs), to analyze concentrations of 14
PBDEs congeners and congener distribution as well as the possible influencing
factors, and to estimate the PBDEs exposure levels of adults and children through
the dust intake. The results showed that the average ?14PBDEs of office was
9.28*102 ng.g-1, and the median was 1.03*103 ng.g-1; the average ?14PBDEs of
family was 7.83*102 ng.g-1, and the median was 9.11*102 ng.g-1; the average
?14PBDEs of student dormitory was 4.07*102 ng.g-1, and the median was 4.03*102
ng.g-1. The pollution level of the office was higher than that of the living
environment. BDE-209 was the largest monomer, and its contribution was 75.48%,
followed by BDE-190, BDE-154 and BDE-71.PBDEs exposure levels of adults and
children by dust intake were 13.12-32.63 ng.d-1 and 32.40-54.54 ng.d-1,
respectively. Children's PBDEs exposure in the dust was higher than that of the
adults, mainly because the average dust intake of children was higher than that
of adults. The analysis showed that the PBDEs from indoor dust intake was a
potential health hazard, and the biggest potential harm to children.
PMID- 29964691
TI - [Evaluating Biochar-Water Sorption Coefficients of Pharmaceutically Active
Compounds by Using a Linear Free Energy Relationship].
AB - A linear free energy relationship (LFER) approach was used to predict the
sorption coefficients of pharmaceutically active compounds (PhACs) to commercial
biochar from aqueous solution, and to investigate the contributions of different
intermolecular interactions in the overall sorption process. 14 PhACs with
diverse functional groups (carboxyl, hydroxyl and nitrogenous heterocyclic) were
selected as sorbates. All isotherm data of PhACs sorption to commercial rice
straws biochar (carbonization temperature: 400-500C, 200 mesh) could be well
fitted by the Freundlich equation. The established LFER model could predict the
value of sorption coefficient lgKd,activity at arbitrary levels of chemical
saturation. The values of multiple correlation coefficient (R2=0.93), standard
error (SE=0.23), F-statistic (268), leave-one-out cross validation (QLOO2=0.90),
external cross validation correlation coefficient (QEXT2=0.92) indicated that the
model was stable and of high predictive ability. The calculated results of the
LFER model showed that, at lower sorbate concentration, sorption was dominated by
the positive effect of cavity and the negative effect of sorbate capability of
electron donation.
PMID- 29964692
TI - [Characteristics of Bacterial Communities in Surface-flow Constructed Wetlands].
AB - Employing high-throughput sequencing as the method, this study analyzed the
relationship between the water environment and the microbial community structure
in the surface-flow constructed wetland. The results showed that: the mean
Shannon-Wiener index was 6.57 and there were mainly 18 categories in the
microbial community, including Proteobacterice (38.97%), Bacteroidetes (15.63%)
etc. Of these, the total content of 22 genera was over 1%. The microbial
biodiversity showed an increasing trend at the beginning and then turned to a
decreasing trend in the flowing direction. The results also revealed that pH,
ORP, NH4+-N, NO2--N and TN acted as important restricting factors for the
microbial community.
PMID- 29964693
TI - [Community Structure and Activity Analysis of the Nitrifiers in Raw Sewage of
Wastewater Treatment Plants].
AB - The communities and activity of nitrifiers collected from the raw sewage of the
2nd and 3rd wastewater treatment plants (WWTP) in Xi'an were investigated. FISH
results indicated that the (AOB+NOB)/EUB percentages were (5.35+/-2.1)% and(6.0+/
2.8)% in the 2nd and 3rd WWTP, respectively. The dominant AOB was Nitrosomonas
europaea/Nitrosococcus mobilis lineage and the dominant NOB was Nitrospira, the
sub-dominant NOB was Nitrobacter, and coexisted with Nitrococcus, Nitrospina.
Respirometric assays showed that the influent nitrifiers were active following a
2-16 hour period of metabolic induction. The ammonium utilized rate was (0.32+/
0.12) mg.(L.h)-1 and (0.43+/-0.17) mg.(L.h)-1, nitrite utilized rate was (0.71+/
0.18) mg.(L.h)-1 and (0.58+/-0.27) mg.(L.h)-1 for nitrifers in raw sewage fed to
the 2nd and 3rd WWTP, respectively. Therefore, nitrifiers were present and active
in the raw sewage, and played the role of natural continuous seeding in the
activated sludge system. Based on the nitrification activity, the estimated
continuous seeding intensity of AOB and NOB was 0.08-0.09 g.(g.d)-1 and 0.11-0.24
g.(g.d)-1, respectively.
PMID- 29964694
TI - [Effects of Fertilization on Soil Microbial Abundance and Community Structure at
DNA and cDNA Levels in Paddy Soils].
AB - Fertilizer applications have important effects on soil microbial abundance and
community structure. In this study, total soil microbial DNA and RNA were
directly extracted from paddy soils of N0 (control treatment, no nitrogen
fertilizer), NPK (balanced fertilization), NPK+LS (balanced fertilization with
additional 3.0 t.hm-2 rice straw incorporation) and NPK+HS (balanced
fertilization with additional 6.0 t.hm-2 rice straw incorporation) treatments in
a long-term fertilization experiment of double rice cropping system in Changsha
County, Hunan Province. Soil bacteria community structures were evaluated by
analyzing the 16S rRNA gene fragments at DNA and cDNA levels with Terminal
Restriction Fragment Length Polymorphism (T-RFLP) and quantitative PCR
techniques. Balancing fertilization with chemical fertilizers and rice straw
incorporation significantly changed the composition of bulk (DNA-based) and
potentially active (mRNA-based) soil bacterial community as shown in T-RFLP
profiles, and also reduced the bulk soil microbial diversity, but not the
potentially active ones, as compared with the control treatment. The DNA-based
abundance of 16S rRNA gene was on average 377 times as many as the m-RNA based
population size. Compared to N0,balanced fertilization with rice straw
incorporation (NPK+LS and NPK+HS) increased the bulk and active copy numbers of
16S rRNA gene, but not for balanced fertilization (NPK). The abundance and
microbial community structure were not significantly different between the NPK+LS
and NPK+HS treatments. Redundancy analysis (RDA) showed that soil ammonium was
the key environmental factor determining the bulk and active soil microbial
community structure among the treatments. In conclusion, the effect of
fertilization on soil microbial abundance and community structure could be
indicated at both DNA and cDNA levels; the cDNA information could better reflect
the adaptability of bacterial community to the environmental stress.
PMID- 29964695
TI - [Effects of Bisphenol A on Characteristics of Paddy Soil Microbial Community
Under Different Cultural Conditions].
AB - Bisphenol A (BPA) is widely known as a typical synthetic environmental hormone.
Effects of BPA concentrations and aerations on soil microbial communities were
rarely reported. This paper presented the studies on effects of various
concentrations of BPA (0, 0.25 mg.kg-1, 0.50 mg.kg-1, 1.00 mg.kg-1, 2.00 mg.kg-1)
and soil aertaiton (aerobic and anaerobic) on characteristics of paddy soil
microbial communites by technology of qPCR (fluorescence quantitative PCR) and
PCR-DGGE (polymerase chain reaction-denaturing gradient gel electrophoresis). The
results lined out that: 1 the microbial abundance index was significantly
different among different BPA concentrations under the same condition of soil
aeration (anaerobic or aerobic). However, the index of microbial evenness,
Shannon-Wiener-diversity and evenness-indices were insignificantly different
under these conditions. At a concentration of 0.50 mg.kg-1, the microbial
abundance index reached a maximum value under anaerobic conditions; while under
aerobic conditions the opposite result was found, the microbial abundance index
dropped to a minimum value. 2 The two-way analysis of variance (ANOVA) showed
that: the concentration of BPA, soil aeration and their interaction significantly
affected the abundance of bacteria, whereas the abundance of fungi was only
affected by soil aeration. The study results showed that: the abundance index was
a sensitive indicator for the variation of soil microbial diversity; it was a
critical value for the change of soil microbial abundance when the BPA
concentration was 0.50 mg.kg-1; as for the abundance of fungi, the response of
bacteria abundance was more sensitive to BPA and soil aeration conditions.
PMID- 29964696
TI - [Identification of a Facultative Bacterium Strain with the Ability to Methylate
Mercury Under Both Aerobic and Anaerobic Conditions].
AB - A strain with the ability to methylate mercury under both the aerobic and
anaerobic conditions was isolated from soil of the water-level-fluctuation-zone
in the Three Gorge Reservoir in Shibaozhai Village, Zhongxian Country, Chongqing,
China (E108 degrees 12'3" and N30 degrees 24'36"). The soil was classified as
Purple soil with a pH of 7.97 (0-20 cm depth). The isolation was performed under
1.0 mg.L-1 HgCl2 conditions. After its morphological and physiological
characterization, and its phylogenetic analysis using 16S rDNA gene sequence, the
strain was identified as Pseudomonas fluorescens sp., and named as Pseudomonas
fluorescens XD-MeHg-B2 (GenBank accession number: KU954349). On one hand, at 30C
under aerobic condition, the concentration of methylmercury (MeHg) in the PBS
(phosphate buffer saline) solution, which was inoculated with 1*1011 cfu.mL-1
suspension of P. fluorescens XD-MeHg-B2 and an initial Hg2+ of 200 ng.L-1, was
exponentially increased to 1.22 ng.L-1+/-0.15 ng.L-1 after 60 min incubation and
then approached to the maximum of 3.85 ng.L-1+/-0.33 ng.L-1 160 min after
incubation. The largest mercury methylation rate was 1.93%. On the other hand, at
30C under anaerobic condition, the concentration of MeHg in the PBS solution,
which was also inoculated with 1*1011 cfu.mL-1 suspension of P. fluorescens XD
MeHg-B2 and an initial Hg2+ of 200 ng.L-1, was 2.86 ng.L-1+/-0.73 ng.L-1 and the
largest mercury methylation rate was 1.43% 180 min after incubation. As a result,
P. fluorescens XD-MeHg-B2 showed its ability to methylate mercury under both
aerobic and anaerobic conditions while with a comparatively hysteretic and lower
ability of mercury methylation. These results demonstrated that P. fluorescens XD
MeHg-B2 could be a promising candidate for further studies on mercury
biogeochemical cycle, particularly under dry-wet alternative conditions.
PMID- 29964697
TI - [Distribution Characteristics of Antibiotic Resistance Genes in Vegetable Soils
in Beijing].
AB - In order to study the distribution characteristics and pollution status of
antibiotic resistance genes (ARGs) in the vegetable soils, greenhouse and field
soil samples in 11 organic vegetable bases with long-term manure amended in
Beijing were collected. All samples were subjected to the determination of 13
type antibiotics and related ARGs. The experimental results showed that
tetracycline residues were the highest among all antibiotics tested, followed by
sulfanilamides. Antibiotic residues were higher in greenhouse soils than in field
soils. For all soil samples, sulfanilamide resistance genes sul 1 and sul 2, as
well as the tetracycline resistance gene tetL were observed with 100% detection
frequencies. Detection frequency for class I integron (intI 1) in greenhouse
soils was 1.5 times higher than that in field soils. The relative abundance for
sul 2 and tetL in soil samples ranged 10-4-10-2 as found by quantitative PCR
(qPCR) detection. The relative abundance of sul 2 was significantly positively
correlated with the contents of sulfadimidine and doxycycline (P<0.05), and the
relative abundance of tetL did not exhibit evident correlation with the contents
of antibiotics tested. These results would contribute to understanding of the
pollution status of ARGs in vegetable soils in Beijing, and to evaluation of
currently agricultural practices based on ARGs.
PMID- 29964698
TI - [Distribution Characteristics of Antibiotic Resistance Genes in Sika Deer Farm].
AB - Sika deer breeding is rapidly developing in South China during the recent years;
however, the impact of sika deer breeding on the abundance and diversity of
antibiotic resistance genes (ARGs) in sika deer farm remains elusive. In this
study, profiles of ARGs were investigated using high-throughput qPCR technique.
The results showed that the abundance of ARGs varied among different samples in
the following order, deer manure composting > deer manure > vegetable soil >
pristine soil, and the profiles of ARGs in these samples were significantly
different (P<0.05). The abundance of ARGs was significantly correlated to that of
mobile genetic elements (MGEs), implicating the potential of horizontal transfer
of ARGs, which might accelerate the dissemination and enrichment of ARGs in the
environment of sika deer farm.
PMID- 29964699
TI - [Comparation of Toxic Effect of Silicious Mineral Dusts on Lung Epithelial A549
Cells].
AB - Considering the high contents of minerals and the potential health risk of
mineral dusts to human and the environment, this paper was aimed to figure out
the toxic effect and mechanism of four common mineral particles (quartz, albite,
sericite, and montmorillonite). Cytotoxicity assays for cell viability (MTT
assay), membrane integrity (LDH assay), oxidative stress (H2O2 assay) and
inflammatory cytokines (TNF-alpha and IL-6 assay) were applied. The results
showed the influence of these mineral particles on A549 cell viability followed
the order of momtmorillonite > cericite>=quartz > albite. There was no obvious
relation between cell viability and the content of SiO2, however, good linear
correlation with the content of iron, and the cytotoxicity of mineral dusts was
strengthened with increasing iron content. Mineral dusts generated H2O2 in cell
or cell-free systems. In particular, H2O2 exhibited a linear correlation with the
iron content, which meant that iron in the mineral dusts played an important role
in the generation of reactive radical. Among those samples, oxidative stress
induced by montmorillonite was distinctly stronger, while there was negligible
influence induced by quartz and albite. Besides, all the tested samples induced
damage to A549 cell membrane, and triggered the release of TNF-alpha or IL-6, but
differed by the kinds of mineral dusts. In conclusion, composition and structure
directly affected, but were not the only factors that contributed to the
biological activity of mineral dusts, the evaluation of cell viability, membrane
damage, free radicals and inflammatory reaction induced by mineral dusts should
take the external morphology, surface active groups, solubility, adsorption and
ion exchange properties into consideration.
PMID- 29964700
TI - [Effect of Adding Compound Adsorbent on Phenanthrene and Cr(VI) Absorption by Lou
Soil].
AB - To study the effect of the addition of compound adsorbent on the phenanthrene and
Cr(VI) adsorption of Lou soil, biochar (made from corn stover) and B200B
(Bentonite modified by BS-12, dodecyl dimethyl betaine with modified ratio of
200% CEC of Bentonite) were mixed at mass ratios of 1:2, 1:1 and 2:1 as the
compound adsorbents (CS1:2, CS1:1 and CS2:1). Different amounts (2%, 5% and 10%)
of these three compound adsorbents were added into Lou soil. Batch method was
used to analyze the phenanthrene and Cr(VI) adsorption isotherms of different Lou
samples, and compare the effect of environmental conditions such as pH value and
temperature on the phenanthrene and Cr(VI) adsorption. The results indicated: 1
Adsorption amounts of Cr(VI) on different Lou samples were 3.02 to 13.61 times
higher than CK (original Lou soil). Under the same adding conditions (amount),
Cr(VI) adsorption showed the order of CS2:1 Lou > CS1:1 Lou > CS1:2 Lou > CK.
Cr(VI) adsorption was a spontaneous process with decreased enthalpy (except
CS1:2) and increased entropy. Adsorption amounts of phenanthrene on different Lou
samples were 3.87 to 13.00 times higher than CK. Phenanthrene adsorption
presented the ranking of CS1:2 Lou > CS2:1 Lou > CS1:1 Lou > CK at the adding
amounts of 2% and 5%, while showed the order of CS1:2 Lou > CS1:1 Lou > CS2:1 Lou
> CK when 10% of the compound adsorbent was added. The adsorption was also a
spontaneous process with decreased enthalpy and increased entropy. 2 When the
temperature was 10-30C, the adsorption amount of Cr(VI) increased by 5.84%, 4.63%
and 8.22% on CK, CS1:1 and CS2:1 Lou soils, and reduced by 2.70% on CS1:2 Lou
soils. Adsorption amount of phenanthrene increased by 1.69% of CK and reduced by
10.55%, 4.36% and 12.81% of CS2:1, CS1:1 and CS1:2 Lou soils respectively. 3 When
the pH was 4-10, the Cr(VI) adsorption had no significant change for CK, while
those for CS1:2, CS1:1 and CS2:1 Lou soils all reduced. Phenanthrene adsorption
of CK, CS1:2 and CS1:1 Lou soils was all highest at pH=4, and phenanthrene
adsorption of CS2:1 Lou was highest at pH=7.4 The higher the ratio of B200B in
compound adsorbent, the better the phenanthrene adsorption was. The higher the
ratio of biochar in compound adsorbent, the better the Cr(VI) adsorption was.
PMID- 29964701
TI - [Effect of Biochar on Adsorption Behavior of Nonylphenol onto Loess Soil in
Northwest China].
AB - In the present study, nonylphenol (NP) was selected as the target pollutant to
investigate the effect of biochar produced from wheat residue at different
temperatures on loess soil based on the batch experiments. The research basically
included adsorption kinetic, thermodynamic and some influencing factors such as
biochar with different pyrolysis temperature, particle size and pH value. The
results showed that the adsorption reaction of NP onto loess soil without biochar
was 10 h during fast reaction, and after the addition of biochar into loess soil,
the fast reaction time of NP adsorption was shortened. Meanwhile, in the fast
stage the adsorption reaction of NP onto loess soil with biochar was
significantly higher than loess soil without biochar, while the difference of
adsorption capacity was small at different carbonization temperatures. The
adsorption reaction of NP onto loess soil by adding biochar could be well
described by the pseudo-second-order kinetics model and reached equilibrium in 16
h. The kinetic data showed that the adsorption of NP accorded well with the
Freundlich isotherm model. The saturated adsorption capacity was improved as
temperature increased with or without biochar. Thermodynamic parameter analysis
indicated Gibbs free energy DeltaGtheta<0, entropy DeltaHtheta>0 and enthalpy
DeltaStheta>0, demonstrating it was a spontaneous, endothermic and chaos
increasing adsorption process. At the same temperature, the adsorption capacity
of NP in loess soils increased dramatically with the increase of carbonization
temperature. The smaller particle size of the loess with the addition of biochar,
the better the adsorption of NP. When the pH value was 4 to 7, the adsorption
capacity of NP onto loess soil by adding biochar showed an increasing trend; in
the pH range of 7 to 10, the adsorption saturation capacity decreased with the
increase of pH value. Therefore, the adsorption of NP on loess with the addition
of biochar had the best adsorption effect in the neutral range. Acid and
alkalinity were not conducive to the adsorption of NP.
PMID- 29964702
TI - [Soil Respiration in Response to Different Ridge/Furrow Ratios and Its
Relationship with Soil Moisture and Temperature Under Ridge-Furrow Planting
Patterns].
AB - This study aimed to explore soil respiration in response to soil moisture and
soil temperature subjected to different ridge/furrow ratios under various
planting patterns. Traditional flat planting and three different ridge-furrow
plantings with altering ridge/furrow ratios, i. e. 20:40 cm (P40); 30:30 cm
(P30); 40:20 cm (P20), were performed in the present study. Soil respirations
among different planting patterns were compared. Their relationships with soil
moisture and soil temperature were also analyzed. The results showed that soil
respiration flux of four planting patterns reached its minimum value during the
wintering stage, started to rise during the returning green stage until it
reached a peak value at the flowering stage, and decreased gradually when
reaching the maturity stage. The magnitude of soil respiration flux in three
ridge-furrow planting patterns followed this order: P40 > P30 > P20, which
implied that increasing ridge width could improve soil respiration by 1.2%-18.4%.
In addition, soil respiration fluxes of three ridge-furrow plantings patterns
were significantly higher than those under conditional patterns during the
seedling stage (P<0.05). The soil temperature of ridge-furrow planting patterns
was higher than that of the conditional flat pattern from the seeding stage to
the wintering stage, but was converse from the jointing stage to the maturity
stage. Moreover, three ridge-furrow planting patterns have shown significant
effect on preserving soil water storage in comparison with the conditional flat
pattern. In general, increasing the width of the ridge increased soil water
storage due to less rainfall from the seedling stage to the jointing stage. The
correlation analysis indicated a positive and significant correlation coefficient
between soil respiration and soil temperature (P<0.01). Correlation coefficients
in case of P40 and P30 were higher than those in P20 and the conditional flat
pattern. The quadratic model of two-factor soil moisture and soil temperature
could explain 61.7%-74.1% of variations in soil respiration. The single factor of
the soil temperature model could explain 50.3%-68.2% of variations in soil
respiration. Those results could provide a theory basis for further evaluation of
ecological effect on the ridge-furrow planting patterns.
PMID- 29964703
TI - [Effects of Straw in Combination with Reducing Fertilization Rate on Soil
Nutrients and Enzyme Activity in the Paddy-Vegetable Rotation Soils].
AB - The effects of straw returning combined the reducing application of chemical
fertilizer for crop yield, soil nutrients and enzyme activity were studied in a
typical southwestern hilly area of China in a rice-vegetable (Brassica juncea
var. gemmifera Lin.) cropping system. The purple soil was selected as the target
type of soil, and the Pioneer Town, Jiangjin District, Chongqing, China was
selected as the typical southwestern hilly area during 2013 and 2014.Scientific
basis based on the optimized fertilization strategy and the recyclable
utilization of straw was provided through a field in-situ experiment in this
study. There were five treatments in the field experiment: F (conventional
fertilizer), 90% F+AS (100% straw with 90% conventional fertilizer), 80% F+AS
(100% straw with 80% conventional fertilizer), 70% F+AS (100% straw with 70%
conventional fertilizer), 50% F+DS (200% straw with 50% conventional fertilizer),
and the 100% straw was 7500 kg.hm-2. The results showed that the yields of rice
and vegetable were all increased in straw with reduced fertilizer treatments
(3.0%-17.9% in rice yield and 12.2%-36.4% in vegetable yield) compared with
conventional fertilizer (F) treatment. Moreover, the yield of rice in the second
season was also increased by 820-1240 kg.hm-2. Soil pH values in straw with
reduced fertilizer treatments raised by 0.06-0.55 compared with F treatment,
especially in straw with 70% and 80% of conventional fertilizer dosage which
increased by 6.74-6.88 and 6.52-6.84, respectively. The highest content of soil
organic matter was 41.01 g.kg-1 in straw with 80% of conventional fertilizer
treatment. For the aspect of soil available nutrients, straw with 80% of
conventional fertilizer treatment increased 110-178 mg.kg-1 content of soil
available nitrogen and 31.3-64.0 mg.kg-1 content of soil available phosphorus.
However, the excessive application of straw had negative effect on the
accumulation of soil available phosphorus. In the same cultivation period, the
contents of soil urease increased significantly in straw with 70% and 80% of
conventional fertilizer treatments, which increased by 13.6%-76.4% and 20.1%
75.0% compared with F treatment. The contents of soil catalase in straw with
reduced fertilizer treatments were significantly higher than F treatment; in
first two seasons, soil catalase contents increased by 0.37 and 0.31 mL.(h.g)-1
relative to F treatment in straw with reduced fertilizer treatment (80% of
conventional fertilizer). With the increasing time of planting, the soil
phosphatase content in the third season was higher than those in first two
seasons. Straw with 70% and 80% of fertilizer treatments increased the activity
of soil phosphatase by 45.2% and 48.2% compared with F treatment. It was
concluded that straw application with 70% or 80% dosage of conventional
fertilizer could benefit the rice-vegetable rotation in the southwest hilly area
of China.
PMID- 29964704
TI - [Spatiotemporal Distribution and Source Attribution of SOA in China].
AB - Secondary organic aerosol (SOA) is an important pollutant due to its significant
impact on atmospheric pollution, climate change and human health. Understanding
the source and distribution of SOA is the prerequisite of air pollution control.
This study utilized the global chemical transport model MOZART4 (Model for Ozone
and Related Chemical Tracers, Version 4) coupled with the parameterizations of
SOA multiphase formation, to simulate the spatial and temporal distribution of
SOA in China, and analyzed the source contributions of SOA from the aspects of
different precursors and regions. Our results indicate that the majority of SOA
production happened over the east and the south China due to the availability of
SOA precursors, with the summertime production a factor of 2.5 higher than that
in winter. Anthropogenic emissions played a dominant role in SOA production,
accounting for 55% of SOA source in China, with the rest from biogenic sources
(45%). The domestic emissions contributed 77% of SOA production in China, mainly
influencing the SOA concentration distribution near the surface of eastern China,
especially over North China Plain. Foreign emissions mainly dominated the SOA
abundance in western China, especially at higher altitudes mainly due to the rare
domestic emission over these areas and the long-range transportation of SOA.
PMID- 29964705
TI - [Emission Inventory of Heavy Metals in Fine Particles Emitted from Residential
Coal Burning in China].
AB - Based on a dilution sampling system and domestic burning tests, emission factors
(EFs) for eleven heavy metals of V, Cr, Mn, Co, Ni, Cu, Zn, As, Cd, Sb and Pb in
PM2.5 from raw coal and honeycoal burning were calculated, using their contents
in raw coals of different provinces. Then the total emission amounts of heavy
metals from residential coals burning in 2012 were calculated and 30 km*30 km
grid cell-based emission inventories were established. The results showed that
the EFs of Pb, Zn, As and Cu were higher from honeycomb coal burning. They were
27.1, 16.8, 0.99 and 0.97 mg.kg-1, which were 56, 6, 10 and 2 times of those for
raw coal, respectively. The total emissions of V, Cr, Mn, Co, Ni, Cu, Zn, As, Cd,
Sb and Pb in PM2.5 from residential coal burning in 2012 were 0.5, 30.1, 59.5,
1.1, 29.3, 20.0, 188.9, 64.9, 1.6, 3.4 and 176.7 t. Hunan, Hebei, Inner Mongolia,
Henan, and Shandong held higher emission amounts, which were 12.4%, 12.3%, 10.4%,
9.9% and 9.3% of the total emissions of the whole country. Beijing, Henan,
Shandong, Hunan, Jiangxi, Guizhou and Inner Mongolia were the regions with higher
emission intensities and emission amounts per capita. The spatial distribution
showed that the regions with higher annual emissions of Zn and Pb distributed
widely, mainly in Inner Mongolia, Hebei, Beijing, Tianjin, Shandong, Henan,
Gansu, Hunan and Jiangxi. The emission inventories for heavy metals in fine
particles established here are important for regional air quality modeling and
human health risk assessment.
PMID- 29964706
TI - [Diurnal Variation of PM2.5 Mass Concentration in Beijing and Influence of
Meteorological Factors Based on Long Term Date].
AB - Diurnal variation of PM2.5 mass concentration is analyzed based on data of
BAOLIAN (representing urban area) and SAHNDIANZI BAP-Station (representing rural
area) from 2005 to 2014. Furthermore, the influence of meteorological factors was
also discussed. The results showed that 10-year-average diurnal variation of
PM2.5 mass concentration in urban area had a two-peak pattern being coincident
with rush-hour. However, it became clear only after 2007. The monthly (including
seasonal) variation presented the change from one-peak pattern to two-peak
pattern with the max mass concentration appearing in the morning or late
afternoon during rush hour. The mass concentration in the morning rush hour
reached its maximum between May and August which was to some degree related with
weak wind and high relative humidity as well as great water vapor pressure
(indicating the absolute water content in the air). But the smaller variety of
mass concentration in the late afternoon attributed to the thicker mixing layer,
higher wind speed and more showers. By contraries, it went up greatly after 4 pm
in Nov., Dec., Jan. and Feb.. One of the reasons was that the height of mixing
layer top decreased sharply. Besides, in some severely and seriously polluted
days, the PM2.5 mass concentration increased after morning rush hour till
afternoon which was different from the mean pattern and that in moderately
polluted day. The main mechanism attributed to the aerosol from aerial source
around brought by south wind to Beijing. The more severe the pollution was, the
greater the daily concentration fluctuated. The range of PM2.5 diurnal variation
was determined by the max wind speed and daily change of relative humidity in a
day. Besides, it also extended the diurnal variation of concentration when the
south wind speed reached 4-6 m.s-1 in the afternoon. In rural area, the mean
diurnal variation of PM2.5 mass concentration showed a one-peak pattern. And the
time of concentration reaching its maximum was ahead of that of urban area.
Moreover, the values in the day time during May and July were higher than that in
winter. These results would be helpful to make policy for finer emission control
when the atmosphere is in lower diffusivity situation.
PMID- 29964707
TI - [Characteristics of Ozone Background Concentration in Beijing from 2004 to 2015].
AB - Based on the hourly O3 monitoring data from 2004 to 2015 of Beijing, a
comprehensive discussion on the characteristics of O3 concentration at a
background station Dingling in Beijing was conducted. The results showed that the
annual concentration of O31h was increasing with a growth rate of 4.40 MUg.m-3
while the annual concentration of O38h was decreasing with annual average rates
of -1.0 MUg.m-3 and -1.5 MUg.m-3 from May to October in 2004 and 2015. Over the
past 3 years, number of O38h severe pollution days increased significantly and
the situation of O3 pollution in Beijing became more serious. O3 concentration
reached its peak in June in a year and its diurnal peak concentration occurred at
about 15:00-18:00 at Dingling station which was 101-1.56 times larger than that
in the urban center of Beijing. In different years, the ozone peak concentration
at Dingling Station was 1h later than that in the urban center from May to
October in diurnal variation and the difference of peak concentration was
significantly reduced in recent years, which on the one hand may be related to
regional ozone pollution, on the other hand may be related to the expansion of
Beijing's urbanization.
PMID- 29964708
TI - [Online Sources about Atmospheric Fine Particles During the 70th Anniversary of
Victory Parade in Shijiazhuang].
AB - Robust measures were taken to ensure a good air quality for the parade on the
70th Victory Memorial Day for the Chinese People's War of Resistance against
Japanese Aggression (VM Day). During the period, the source of fine particulate
matter in air was analyzed with the single particle aerosol mass spectrometer
(SPAMS) located at Shijiazhuang air automatic monitoring station of 20 meter. The
results indicated that, on VM Day the primary sources of air pollution were
vehicle exhaust emission (20.9%) and coal-generated emissions (20.6%), which were
also at lower degrees than those on pre-and post-VM Day. It turned out that these
air quality-improving measures, especially the vehicle restriction and coal
consumption reduction, had a good effect. Particles from the vehicle exhaust and
coal combustion source were mainly based on short-chain elements, carbon,
manganese and organic carbon. The particles from the industry source were mainly
organic carbon and metal. Particles from the dust source were mainly composed of
silicate and calcium. When air quality-improving measures were stopped, the
concentration of particulate matter rapidly rose again, and the contribution of
dust and vehicle exhaust emission was remarkable. It was believed that the
interaction of low-pressure static stability of adverse weather conditions and
southeast direction of low altitude transmission was a major cause in the
deterioration of air quality.
PMID- 29964709
TI - [Pollution Characteristics of Inorganic Water-soluble Ions in Atmospheric
Particulate Matter in Chengdu Plain].
AB - To study the pollution characteristics of water-soluble ions in atmospheric
particulate matter in Chengdu Plain, and identify the composition, distribution,
time and spatial variation, achieve targeted control of heavy pollution and haze
days, 1476 samples were collected at five monitoring sites during August 2013
July 2014, in which eight kinds of inorganic water-soluble ions (SO42-, NO3-,
NH4+, K+, Na+, Ca2+, Mg2+, Cl-) were determined by ion chromatography. The
results showed that the total mass concentrations of 8 ions in PM2.5-10 and PM2.5
were 11.35 and 36.93MUg.m-3, accounting for 37.8% and 46.6% respectively, and SNA
(SO42-, NO3- and NH4+) in PM2.5-10 and PM2.5 contributed 81.1% and 89.9% to the
total ions, respectively. The concentration of water-soluble ions was highest in
winter and lowest in summer. rho(SO42-)/rho(PM2.5) was highest in summer and
autumn, while rho(NO3-)/rho(PM2.5) was highest in winter and lowest in summer.
SNA, Cl-, K+mostly distributed in PM2.5, Ca2+ and Mg2+ in PM2.5-10. PM2.5 was
generally neutral, the water-soluble ions in which existed as (NH4)2SO4, NH4NO3,
KNO3, NaCl, KCl and so on. rho(NO3-)/rho(SO42-) revealed that the main source of
PM2.5 was given priority to fixed sources. Sulfur oxidation ratio (SOR) and
nitrogen oxidation ratio (NOR) were 0.31 and 0.13, respectively, which had
opposite changing trend with a highest SOR in summer and NOR in winter. PM2.5 had
the characteristics of regional pollution complex, and SNA was the dominant
factor causing the increase of rho(PM2.5).
PMID- 29964710
TI - [Observation Analysis on the Characteristics of Meteorological Elements and
Pollutants During a Continuous Fog and Haze Episode in Spring in Jiaxing City].
AB - A continuous fog and haze episode occurred on 17-20 May, 2015 in Jiaxing. Trace
gases (O3, CO, SO2 and NO2), PM10, PM2.5, aerosol number concentration in the
range of 10 nm-10 MUm, meteorological elements, and radiosonde data from the 17st
to the 22st of May were used to analyze the formation mechanism and pollutant
characteristics during this episode. The results showed that subtropical high
pressure lifted northward, a field pressure was dominant over Jiaxing leading to
a weak ground wind speed, and a strong inversion layer occurred, this supplied
moisture, power and thermal conditions for the occurrence and maintenance of the
event. The episode included one precipitation process and two fog processes
(rainy fog and radiation-advection fog). During the fog and haze process, the
concentrations of NO2, CO, PM10 and PM2.5 were high and the levels of SO2 and O3
were low. Strong precipitation had greater scavenge effects on PM10, PM2.5 and
SO2, while weak precipitation aggravated the pollution degree. The PM
concentrations increased continuously during the rainy fog process, while it
decreased firstly and then increased during the radiation-advection fog process.
The spectral distributions of aerosol number concentration were unimodal and
differed significantly under different types of weather conditions. The peaks of
number concentration were located at 20-30 nm, 100 nm, 30-60 nm, 120 nm, 90 nm
under clean, precipitation, fog and haze, rainy fog, radiation-advection fog
conditions, respectively. The spectra of surface area concentration were trimodal
under clean, precipitation, fog and haze, rainy fog conditions, and had four
peaks under radiation-advection fog condition.
PMID- 29964711
TI - [Characteristics and Source Apportionment of Metals in the Dustfall of Quanzhou
City].
AB - Concentrations of 23 metal elements in the dustfall collected from different
functional areas of Quanzhou City, China, were determined. Several methods were
applied to assess the enrichment degree, pollution level and potential ecological
risk of the above elements. The sources of the above elements were analyzed based
on the multivariate statistical analysis combining Pb and Sr isotopic tracing
technology. The results showed that the concentrations of metals in the dustfall
presented significant spatial difference. The results of enrichment factor and
geo-accumulation index indicated that Cd, Hg, Zn, Ca, Pb, Cu, Ni and Sr showed
relatively higher enrichment degree and pollution level. The results of
ecological risk index showed that the comprehensive ecological risk of heavy
metals was very high in the dustfall of all functional areas with the sequence of
industrial area>heavy traffic area >commercial area >residential area >scenic
area >agricultural area. Cd and Hg showed extremely high potential ecological
risk, and they contributed 95.56% to the comprehensive potential ecological risk
index. The multivariate statistical analysis demonstrated that the elements of V,
Fe, Ba, Bi, Ni, Sr, Pb, Cs, Sc, Zn, Cd were mainly from industrial and vehicle
emissions; Th, U, Rb, Y, Ti were mainly derived from soil dust; Li, Mn, Cu, Hg,
Cr, Co, Ca were mainly from coal combustion. The contribution ranges of parent
soil, coal combustion and vehicle emission to the Pb in the dustfall were 29.41%
64.00%, 22.53%-60.48% and 3.13%-13.47%, respectively, as calculated by a ternary
hybrid model; The plots of 87Sr/86Sr vs 1/Sr showed that Sr in the dustfall was
dominated by coal combustion and vehicle emission.
PMID- 29964712
TI - [Level and the Courses of Heavy Metals and Its Risk Assessment in Indoor Dust of
City: Take Guiyang as a Case].
AB - A total of 73 household dust and 6 office dust were collected and the
concentrations of Ca, Fe, Cd, Cr, Cu, Ni, Pb and Zn were measured by ICP-OES, in
order to study the levels of heavy metals in city indoor dust and assessits risk
from indoor and outdoor dust to children. The result showed that: 1 The
concentrations of Ca, Fe were 107, 31.9 g.kg-1 and those of Cd, Cr, Cu, Ni, Pb
and Zn were 1.77, 107, 231, 81.9, 199, 721 mg.kg-1, respectively. 2The levels of
Cu and Zn in office dust were significantly higher than those in household dust,
and the levels of other elements had no obvious difference from those in
household dust. 3The levels of Ca and Fe in household dust with different floor
numbers were not significantly different, but the levels of Cd, Cu and Pb in
household dust with different floor numbers had obvious difference. The levels of
elements in household dust from 1th floor were relatively higher, and the level
of Pb in household dust from higher floors was higher than that on lower floors.
4Outdoor environment, indoor decoration and life styles may cause the difference
of elements level in different household dust. 5There was no obvious risk from
heavy metals in dust to children.
PMID- 29964713
TI - [Chemical Characteristics and Source of Acid Precipitation in Guilin].
AB - A total of 396 rainwater samples of Guilin from 2008 to 2011 were collected and
analyzed for pH, 44 of which were analyzed for major ions. The analysis of pH
values showed the obvious seasonal variation of acid rain in Guilin. The
pollution level of summer was lower than those in other seasons, while the
pollution levels in winter and spring were the highest. The investigation of
fractional acidity(AF) and neutralization factors(NF) indicated that low acid
rain pollution level in 2008 was caused by alkali neutralization, especially NH4+
and Ca2+. Studies of the origins of major ions showed that CI- and Na+ were
mainly from sea, Ca2+ was mainly from the crustal dust while K+, SO42- and NO3-
were mainly originated from anthropogenic source. Finally, the effect of regional
transportation on acid rain of Guilin was analyzed and 3 originatons of acid
causing substance were oriented by an air trajectory clustering methodology based
on hysplit-4 and a clustering algorithm including 1Jiangxi, Anhui, Hunan and
Hubei, with high population densities, these regions contributed 19% air mass in
spring, 26% in summer, 19% in autumn and 36% in winter due to the northeast wind;
2Pearl River Delta, with airflow from west Pacific passing before arriving
Guilin, contributing 19% in spring, 33% in autumn and 36% in winter; 3Nanning,
Liuzhou. All strong acid rain vapor air mass converged in southwest Guilin in
spring, and arrived in Guilin passing Naning and Liuzhou. In summer, under the
direct control of southwest monsoon, the vapor from Indian Ocean directly arrived
in Guilin, accounting for 75%. The southwest airflow passing these cities
accounted for 14% in autumn and 63% in winter.
PMID- 29964714
TI - [Assessment of Gaseous Nitrogen (NH3 and N2O) Mitigation After the Application of
a Range of New Nitrogen Fertilizers in Summer Maize Cultivation].
AB - In order to evaluate the potential of a range of new nitrogen fertilizers in
comparison with the conventional fertilization to mitigate ammonia (NH3) and
nitrous oxide (N2O) emissions, a field experiment was conducted to investigate
NH3 volatilization and N2O emissions from the summer maize field and the relevant
driving factors under the different nitrogen fertilizer treatments. Five new
varieties of nitrogen fertilizers including the urea ammonium (UA), stability
urea with dicyandiamide and hydroquinone (UHD), sulfur coated urea (SCU), urea
formaldehyde compound fertilizer (UF) and organic fertilizer (OF) were applied in
this experiment, and conventional fertilization (compound fertilizer + urea, CK)
was used as the control. The nitrogen amount of 300 kg.hm-2 was applied in all
treatments. Correlation analysis results showed that both NH3 volatilization and
N2O emissions were influenced by environmental factors. They were negatively
correlated with soil water-filled pore space (P<0.05). Moreover, N2O emissions
were positively correlated with soil nitrate nitrogen (P<0.01). Regression
analysis showed that N2O emissions were mainly determined by the soil nitrate
content, while NH3 volatilization was mainly dependent on the values of soil
ammonium nitrogen. Compared with CK, in addition to UA, other fertilizer
treatments decreased the NH3 volatilization, especially the UF and OF treatments
decreased NH3 volatilization by up to 37%-43%, while all treatments had no
significant difference in N2O emissions. Considering the total gaseous nitrogen
losses (NH3 volatilization + N2O emissions), in comparison with CK, the UHD, SCU,
UF and OF were reduced by 9%, 5%, 30% and 23%, respectively, while the UA was
increased by 3%. Therefore, considering environmental benefit under this
experimental condition,urea formaldehyde compound fertilizer and organic
fertilizer were more suitable for maize cultivation.
PMID- 29964715
TI - [Soil CO2,CH4 and N2O Fluxes from Alpine Meadows on the Plateau of Southern
Qinghai Province During Snow Cover Period and Growing Seasons].
AB - To understand the fluxes of soil greenhouse gases from Alpine meadows on the
Qinghai-Tibet plateau during non-growing season, a static chamber method was used
to sample gases of soil CO2, CH4 and N2O from alpine meadow on the plateau of
Southern Qinghai province during snow cover period, and gas chromatography was
used to analyze concentrations of these gases. The results showed that soil CO2
flux was 1.33 g.(m2.h)-1, soil CH4 flux was -0.19 mg.(m2.h)-1, and soil N2O flux
was 0.21 mg.(m2.h)-1 when the snow depth was 9-10 cm on March 3 and 4 during the
prevalence period of snow cover; soil CO2 flux was 4.70 g.(m2.h)-1 ,and soil N2O
flux was 0.24 mg.(m2.h)-1, and soil CH4 flux was -1.23 mg.(m2.h)-1 when the snow
depth was 8-9 cm on April 30 during the end period of snow cover. And soil CO2
and N2O fluxes were low or negative, soil CH4 flux was negative and its absolute
value was low when the snow depth was less than 4 cm during snow cover period. In
addition, soil CO2 or N2O flux was positively correlated with the snow depth, and
soil CH4 flux was negatively correlated with the snow depth (P<0.05).
Additionally, soil CO2 or N2O flux was negatively correlated with CH4 fluxes, and
soil CO2 was positively correlated with soil N2O flux. In addition, soil CO2 flux
was the highest during the growing season, followed by the end period of snow
cover, and it was the lowest during the prevalence period of snow cover; soil N2O
flux was high during the growing season, followed by the end period of snow
cover, and it was the lowest during the prevalence period of snow cover; soil CH4
flux was negative, and its absolute value was higher during the growing season
than other seasons, and it was the lowest during the prevalence period of snow
cover. The results suggested that the change in snow cover would influence the
fluxes of soil greenhouse gases from alpine meadow on the Qinghai-Tibet plateau.
PMID- 29964716
TI - [Partial Pressure of Carbon Dioxide and Methane from Autumn to Winter in Xiangxi
Bay of the Three Gorges Reservoir].
AB - The Concentrations of dissolved CH4 and CO2 in Xiangxi Bay of the Three Gorges
Reservoir from autumn to winter in 2014 were determined with headspace gas
chromatography technology. Then their partial pressures of CH4 and CO2 were
calculated according to the Henry's law. Their temporal variation and the effects
of environmental parameters were also discussed. The results indicated that the
CH4 partial pressure in the surface water ranged 0.64-4.43Pa, with an average of
(1.69+/-0.94)Pa. The CO2 partial pressure varied from 49.90 to 868.91Pa, with the
average of (328.48+/-251.63)Pa. The pCO2 and pCH4 had a strong negative
correlation (r=-0.618,P<0.01). During the period of monitoring, the pCO2 and pCH4
in surface water were significantly correlated with pH, DO, chlorophyll a, TP,
surface water temperature and water level. Compared with pCH4, pCO2 was more
closely correlated with various environmental factors.
PMID- 29964717
TI - [Potential Impacts of Climate Change on Phosphorus and DO in Yuqiao Reservoir].
AB - The climate indicators and water quality parameters, e.g. total phosphorus (TP)
and dissolved oxygen (DO) in a period of 20 years (1992-2011) were analyzed to
explore potential impacts of climate change on nutrients and DO. Firstly, the
study period was divided into two decades: 1992-2001 cool decade and 2002-2011
warm decade for the Mann Kendall statistical test and the accumulative anomaly
test. Secondly, the significance of climate parameters in seasonal variations was
analyzed by comparing the nonlinear trends of parameters using non-parametric
regression in two decades respectively. Finally, comparing the relationship
between climate indicators and water quality parameters for two decades, the
potential impacts were investigated by double-k method. The results showed that
the higher temperature potentially decreased TP concentrations in winter and
spring and DO concentration in autumn. However, the increases in air temperature
in winter and spring increased DO concentration. The increase in wind speed was
most likely to increase TP and DO concentrations in all four seasons. A positive
correlation between precipitation and TP concentration was found in all four
seasons. The DO concentration declined when rainfall decreased in summer. The
difference in temporal trends between inflow P loading and concentrations in
reservoir indicated the potential impacts of climate change on TP concentration.
The field data in TP and macrophytes biomass in spring was the evidence
supporting that TP in spring was likely to decline when the air temperature
increased. The study provides a reference for the impacts and mechanisms of
climate change on water quality in Yuqiao reservoir.
PMID- 29964719
TI - [Response of Inflow Water Quality to Land Use Pattern in Northern Watershed of
Lake Erhai].
AB - The inherent relationship between land use pattern and inflow water quality is
essential for nonpoint source pollution study. Response of inflow river quality
to land use pattern in Northern part of Lake Erhai Watershed was analyzed in
aspects of land use composition and configuration using spatial analysis and
statistical analysis methods. The results indicated that as land use composition
indexes, average slope and vegetation area percentage had significant
relationship with TN and TP of inflow rivers. As land use configuration indexes,
patch density, patch density of agriculture land and landscape shape index of
water had significant relationship with TP and NH4+-N of inflow rivers. Response
of inflow river quality to land use pattern was better at class level than at
landscape level. Water quality response indicators were TP in rainy season and
NH4+-N in dry season, of which regression adjustment coefficient R2 was 0.761 and
0.978, respectively. Response of inflow river quality to land use pattern was
better in dry season than in rainy season, and the water quality response
indicators were TN, TP and NH4+-N. Improving vegetation coverage and agriculture
land intensive degree and avoiding human disturb to natural water area especially
in dry season were suggested in nonpoint source pollution control of northern
watershed of Lake Erhai Watershed. Later research on relationship between land
use configuration and inflow river quality should better be at class level.
PMID- 29964718
TI - [Land Use Structure Change and Its Control Effect of Nitrogen Output in a Small
Watershed of Three Gorges Reservoir Area: A Case Study of Lanlingxi Watershed].
AB - The nitrogen (N) output in Lanlingxi watershed of Three Gorges Reservoir Area in
2015 was monitored and the current land use map was investigated. Cluster
analysis and correlation analysis were used to identify the major sources of
pollutants and to discriminate the source and the sink land use types. The
effects of land use on N exports were quantitatively analyzed by stepwise
regression analysis. The results showed that: 1 After the returning farmland to
forest project the land use structure of this area changed dramatically. The area
proportions of forest land and garden plot increased to 76.85% and 13.87%
respectively, and the proportion of cultivated land dropped to 1.16%. Cultivated
lands were stellate distributed and garden plots in some catchments were flake
distributed. 2 The content of TN in some monitoring points surpassed the Class V
standard of the national groundwater environmental quality. The ammonium-N (NH4+
N) concentrations ranged 0.089-0.214 mg.L-1, 2.925-13.203 mg.L-1 for nitrate-N
(NO3--N) and 3.561-14.572 mg.L-1 for total-N (TN). And NO3--N accounted for more
than 80% of TN. 3 There were significant positive correlations between garden
plot, residential land and N loss, and negative correlations between forest land,
unutilized land and N export, which indicated that the former were N sources and
the latter were sinks. 4 Forest land area should be increased and garden plot
should be controlled, and the area ratio of residential land should be kept below
5% when adjusting land use structure of this watershed. Moreover, forest-tea and
forest-fruits modes should be applied to change single land use type of garden
plot in some catchments.
PMID- 29964720
TI - [Effect of Nutrient Cycles in Tributaries on the Transport of Nutrient in the
Three Gorge Reservoirs:A Case Study of Caotang River].
AB - Backwater regions have been formed in the downstream of tributaries since the
Three Gorge Reservoir (TGR) was impounded, as the most influential area to the
aquatic environment within the reservoir. In order to study the effects and
significance of the backwater regions on the nutrient cycling and substance
fluxes, dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP),
dissolved silicon (DSi) were monitored in situ in Caotang tributary backwater
region, the adjacent mainstream and Caotang tributaries' upstream every month
from August 2012 to July 2013. The results showed that the concentrations of DIN,
DIP and DSi in Caotang tributary backwater region were similar to those in the
mainstream, and the monthly variation tendency was very consistent with the
mainstream Changjiang. DIN, DIP and DSi in the Caotang tributary were mainly
originated from the mainstream. The influence of the mainstream water could
extend to the upmost of the backwater region due to the good connection and
rapid, sufficient water exchange between mainstream and tributary. Nutrients from
the mainstream were retained and consumed by primary producers in the tributary
during the growing seasons in spring and summer, while released back to the water
during late autumn and winter. Nutrient cycling in the tributary could change the
seasonal pattern of nutrient transportation. The mainstream nutrient fluxes could
receive significant seasonal modification from the large numbers (more than 40)
of tributaries within the TGR domain.
PMID- 29964721
TI - [Transient Storage Characteristics of Artificial Pool Geomorphic Structure in an
Agricultural Headwater Stream].
AB - From November 2015 to February 2016, five short-term tracer injections were
performed with a conservative tracer (NaCl) in an agricultural headwater stream,
Lake Chaohu basin. Thus the data sets of tracer experiments were finally employed
for calculating the physical characteristics and transient storage metrics.
Through the comparisons between the artificial pool reach and straight reach,
characteristics of transient storage for the artificial pool geomorphic structure
were interpreted and explored. Study results showed that: 1 The ratio of As/A in
artificial pool was larger than that in straight reach, whereas its value of
exchange coefficient alpha was lower by an order of magnitude than that of
straight reach. 2 Artificial pool geomorphic structure had greater influence of
transient storage on solute retention than that in straight reach, but its solute
retention capacity of flowing water was weaker than that of straight reach. 3 It
had a large ratio of As/A for the pool geomorphic structure, whereas its impact
on the migration and transformation of solutes was less than that of straight
reach. 4 Based on the Fmed200 metric, the transient storage accounted for 18.86%
to 26.05% of travel time in artificial pool. For the straight reach, the Fmed200
metric had a range of 5.28% to 33.87%. In most cases, the values of Fmed200
metric in straight reach were higher than those in artificial pool. 5 Significant
differences existed between artificial pool geomorphic structure and straight
reach in the values of phiw, phiA and Ts, however, the differences were not
significant in other indicators.
PMID- 29964722
TI - [Distribution Characteristics of Solute Nitrogen in the Water-Sediment of
Farmland Drainage Ditch].
AB - Along with the highlighted water environmental issues and the gradual effective
renovation of the point source pollution (PSP) such as industrial waste, the
agricultural non-point source pollution (AGNSP) caused by the non-scientific
application of fertilizers and pesticides has attracted more and more attention.
On the basis of strengthening the field "source control", making the best use of
agricultural drainage ditch (pond) system "intercepting process" is a vital means
of agriculture non-point source pollution control and management at the present
stage. Ditch system is not only an important part of the farmland irrigation and
drainage engineering, but also a vital corridor of AGNSP of solute transport. The
unique farmland drainage ditch water-sediment-plant system in ecology and physics
is similar to linear wetland function,and has effect of interception and
purification on non-point source solute in farmland drainage. Non-point source
solute transformation mechanism of each medium in the farmland drainage ditch
water-sediment-plant system is unclear, in view of the current situation, the
study took the natural channel as the object. Taking the non-point source solute
nitrogen as an example, by field monitoring test during March 2014-February 2015,
the distribution characteristics of non-point solute nitrogen in the water
sediment of the farmland drainage ditch were analyzed. The results indicated that
the concentration of total nitrogen in water and the total nitrogen content in
the sediment of the experimental ditches both showed a certain degree of
decreasing trend along the longitudinal ditch, which represented a purification
effect of the ditch system on the non-point source solute. The concentration of
total nitrogen in water and the total nitrogen content in the sediment had big
inhomogeneity in the ditch cross-sectional distribution, and its distribution
characteristics were related to the shape of the cross-section, flow variation
process, flow velocity distribution and other factors. The balance of the total
nitrogen concentration was 76.89%, and the total nitrogen content in the sediment
was 57.04%. During the trial period, the total nitrogen concentration in the
water was "concave" shape, while in the sediment it was "convex" shape, showing
opposite changing trends.
PMID- 29964723
TI - [Characteristics and Influencing Factors of Soil Microbial Biomass Carbon and
Nitrogen in Drawdown Area in the Three Gorges Reservoir].
AB - Taking a typical drawdown area located in Wangjiagou of the Three Gorges
Reservoir as the study object, four elevations 180,175,165 and 155 m were
selected to explore the effect of water level change on soil microbial biomass
carbon (SMBC) and microbial biomass nitrogen (SMBN). Wherein, 175,165 and 155 m
elevations located in the fluctuating zone, manifested as short, medium and long
term flooding, respectively; 180 m was used as the control, located on the land
and never flooded. Sampling depth in soil samples was 0-20 cm, collected once a
week. The results indicated that, soil organic carbon (SOC) and total nitrogen
(TN) contents at 180 m had no obvious seasonal changes, while they showed
remarkable seasonal trends at 175m, which in spring and summer were significantly
higher than in autumn and winter; SMBC and SMBN contents and their allocation
ratio at four elevations were similar and had significant seasonal fluctuation,
which were highest in autumn and lowest in summer at each elevation, indicating
that in drawdown area the microbial activity and turnover rate of soil organic
carbon and nitrogen were limited by the high-temperature and low-humidity soil
environment in summer. Data analysis showed that, compared with the 180 m
elevation, contents of SOC, TN, SMBC and microbial quotient, SMBN and its
allocation proportion showed varying degrees of increase, while contents of these
indexes were significantly lower than control except SMBN and its allocation
proportion, meaning that compared with 180 m short and medium-term flooding was
conducive to improve soil carbon, nitrogen and their turnover rate and microbial
biomass, however, contents of soil carbon and nitrogen and microbial biomass
carbon were significantly restricted at 155 m as soil was subjected to flooding
stress, meanwhile the turnover rate of SOC was reduced. Correlation analysis
implied that SMBC and SMBN had very significant negative correlation with
temperature at 5 cm soil depth and pH, meaning that the two environmental factors
had a strong effect on soil microbial biomass.
PMID- 29964724
TI - [Response Behaviors of Heavy Metals at Tidal Currents Interface and Salinity
Interface in the Estuary Area].
AB - In China, trace metals (such as dissolved Cu, Zn, Pb, Cd, and Cr) are the routine
mandatory monitoring indicators in existing Freshwater Quality Standard (FWQS,
2002) and Seawater Quality Standard (SWQS, 1997). Using Daliao River estuary as
an example, we tried to research the general response patterns of these metals in
estuarine system. Firstly, we determined the location of FSI (freshwater-seawater
interface) and TCI (tidal currents interface), which were based on biological,
chemical and geographic similarities by descriptive and quantitative methods,
respectively. Secondly, two hypotheses were proposed to explain the difference
based on distribution coefficient Kd along salinity and SS (suspended solids)
gradient, these results revealed that the indicators for As, Cd and Cr may be
prone to be affected by salinity, and the ones in the second pattern may be more
sensitive to SS. Finally, we classified the response behaviors into two patterns
based on the changing trends along the distance and magnitudes affected by the
FSI and TCI: 1the obvious boundary break point from FSI for As, Cd and Cr; 2 the
boundary zones from TCI for Zn, Cu, Pb and Ni. The partitioning behaviors showed
similar changing trends at particle and sediment phases, especially for particle
phase, depending on the concentration of SS along the salinity. The difference
between general behaviors for the two patterns mainly existed at water phase. In
general, this paper highlighted the need to consider the background difference of
trace metals and identified the sensitive indicators controlled by different
environment factors (such as salinity and SS) based on the native estuarine
characteristics. Our work will assist the implementation of updating the current
water quality standards in China.
PMID- 29964725
TI - [Simulation of Multimedia Transfer and Fate of Perfluorooctane Sulfonate (PFOS)
in Shenzhen Region].
AB - To study the transfer and fate of perfluorooctane sulfonate (PFOS) in Shenzhen
region, a level III fugacity model was used to simulate and calculate the
concentrations of PFOS in local air, water, soil and sediment. Physical and
chemical parameters of PFOS and environmental parameters of Shenzhen were entered
into the model. The simulated concentrations were compared with actual
measurements to validate the model, and then analyzed based on the transfer flux
of PFOS between media to identify the main transfer route. The input parameters
and output results of the model underwent sensitivity analysis and uncertainty
analysis, respectively. The simulated concentrations of PFOS in air, water, soil
and sediment were 1.4 pg.m-3, 7.0 ng.L-1, 0.39 MUg.kg-1 and 0.11 MUg.kg-1, in
good agreement with the actual measurements. The transfer from air to soil, soil
to water and air to water were the main PFOS transfer routes between media,
accounting for 32%, 32%, 5.8% of total transfer, respectively. The transfer
through water was the major PFOS outlet from a region. The advective input of air
and water, temperature, PFOS solubility, precipitation and density of soil and
sediment were the key parameters affecting the model output. Uncertainty analysis
showed that the coefficient of variation of PFOS concentrations reached the
minimum in water and the maximum in soil, which may be caused by the highly
changeable content of organic carbon in soil.
PMID- 29964726
TI - [Distribution Characteristics and Ecological Risk Assessment of Organochlorine
Pesticides in Surface Sediments of Zhelin Bay in Guangdong Province, China].
AB - The distribution characteristics and pollution degrees of 20 organochlorine
pesticides (OCPs) were investigated in surface sediments from Zhelin Bay south of
China and the ecological risk of OCPs and integrated ecological risk at the
samples stations in sediments were evaluated by risk quotient (RQ) and sediment
quality guideline of NOAA. The possible sources of HCHs and DDTs in sediments
were preliminarily studied, and the correlation between OCPs and sediment
characteristic parameters was discussed. The concentrations of DDTs in surface
sediments were found to be higher than those of other OCPs, especially p,p'-DDD,
and the concentrations of DDTs were higher than the limited values of Chinese
Marine sediment quality criteria. The total concentration of 20 OCPs in surface
sediments ranged from 14.14 to 306.88 ng.g-1, with a mean concentration of 78.37
ng.g-1, and the highest total concentration was at site 8(S8). There were
inevitable adverse biological effects and high ecological risk of p,p'-DDD and
p,p'-DDT, high integrated ecological risk at S8 and S10. The possible sources of
HCHs in surface sediments of Zhelin Bay were mainly from the application of
Lindane pesticides. At S1,S2,S10,S11 there was input of DDT into mariculture area
of Zhelin Bay, and at the other sites the sources of DDT were from the early
residue in sediments or the long-term weathering sediments of using pesticides.
There was a very significant positive correlation between HCHs, endosulfan,
chlordane and dieldrin in sediments, while there was a negative relation between
the above OCPs and TOC, which indicated that the presence of TOC could promote
their biodegradation. There was a significant positive correlation between p, p'
DDD and Ca, which revealed that DDT used in the early period was deposited with
biological carbonate. Increasing size of sediment particles discouraged the
accumulation and enrichment of OCPs in sediments.
PMID- 29964727
TI - [Spatial Distribution Characteristics and Source Analysis of Dissolved Organic
Matter in Beiyun River].
AB - Dissolved organic matter (DOM) in aquatic ecosystems has gained wide concern
because of its influence on the light attenuation, nutrient availability and
contaminant transport. Human activities strongly influence the DOM of rivers in
different ways, including increased agricultural activities and industrial and
domestic emissions. However, recent socio-economic development with rapid urban
development has significantly enhanced the discharge of sewage, and has caused
high loads of DOM, which in turn pose a great risk to aquatic ecosystems. To
effectively guide water management for protecting aquatic ecosystem health, it is
very critical to investigate the distribution and source of dissolved organic
matter in urban rivers. In this study, the distribution and source analysis of
DOM in Beiyun River were evaluated, where covers the most populated area with a
population of 14 million, representing the most urbanized watershed of Beijing.
Since the main receiving source of the river is treated and untreated wastewater
in Beijing City, the water quality is highly polluted by anthropogenic inputs.
However, information on DOM of Beiyun river has not been reported. Therefore,
this study can not only reveal the biogeochemistry of DOM in Beiyu River, but
also provide useful implications of pollution control for similar urban rivers.
The fingerprint features were extracted from the Excitation-Emission Matrix
Spectrum of fluorescent dissolved organic matter (FDOM) in 23 sampling sites of
Beiyun river during November 2013. Three separate fluorescent components were
identified by Parallel factor analysis (PARAFAC) model, including two humic-like
components (C1: 240, 300/385 nm; C2: 255, 350/400 nm) and one protein-like
component (C3: 230, 280/340 nm). The results indicated that humic-like materials
were generally the dominated component of FDOM, accounting for 76.18% of the
average total fluorescence intensity. Positive relationships were found between
the fluorescence intensity and the concentrations of some water quality
indicators, such as total nitrogen, ammonia nitrogen and total phosphorus,
indicating the same sources of these components. Thus, the migration and
transformation of nitrogen & phosphorus could also influence the level of FDOM.
The distribution of total fluorescence intensity showed a distinctly different
spatial pattern. The fluorescence intensity decreased firstly along the upstream
to midstream continuum, and then increased from the midstream to downstream. The
FDOM in the upstream could be attributed to the industrial effluent and
agricultural runoff inputs. Among the upstream to downstream continuum, the
content of FDOM in the midstream was the lowest. Limited domestic pollution was
suggested as the major source. In the downstream, the sources of FDOM could be
interpreted as industrial, agricultural wastewater and livestock wastewater
discharge. The relative abundance of protein-like materials was markedly
increased in this area, indicating the sources of DOM was highly impacted by
human activities. In addition, our study also concluded that the removal
efficiency of DOM in wastewater plants is not very desirable, which implied that
stronger support for DOM removal in sewage system is needed to alleviate DOM
pollution and improve water quality.
PMID- 29964728
TI - [Distribution and Environmental Significances of Radionuclides in the Sediment of
the Changyi Coastal Wetland].
AB - The radionuclides contents in the surface sediments and sediment cores were
determined by gamma spectrometry method. The distribution of radionuclides and
its indication to material sources, human activities and other sedimentary
environmental evolution events were discussed and the sedimentation rate was
estimated. The results showed that the average activity concentrations of
238U,232Th, 226Ra and40K in the surface sediment were (54.4+/-11.7), (57.9+/
9.7), (28.6+/-4.3) and (542+/-21) Bq.kg-1, respectively. Regional differences of
radioactivity level reflected the material sources and influences of human
activities on the sediment characteristics. According to the vertical
distribution of excess 210Pb, the sedimentation rate of high tidal areas was
estimated at 0.23 cm.a-1. In the sediment core, the variable coefficients of
238U,232Th and 226Ra contents were high. According to the vertical profiles of
238U,226Ra and 238U/226Ra ratio, the process of sedimentation could be divided
into four periods: period of slow deposition, period of dramatic change in
sedimentary environment caused by great migration of the Yellow River channels,
period of stable deposition after the Yellow River ran into one single channel,
and period of alternate degradation and growth under the influence of human
activities. The vertical variation of radionuclides in the sediment core could
serve as an effective environmental indicator since it could record the
environmental evolution processes of the coastal wetland.
PMID- 29964729
TI - [Fecal Contamination in Laolongdong Underground River as Measured by the Sterol
Biomarkers].
AB - To investigate whether the underground river was polluted or not, and trace the
source of fecal sterols, the particulate water samples were collected from
typical karst underground river named Laolongdong in Nan'an District, Chongqing
Municipality in October, 2014, January, March and May, 2015. Ten prior steroids
in the underground river were quantitatively analyzed by the gas chromatography
mass spectrometer (GC-MS). The results showed ten steroids including 9 sterols
and 1 ketone were detected. During the sampling period, the mass concentrations
of particulate steroids (ranging between 1573 and 5007 ng.L-1) in March and May
were higher than those in October and January. The 3 principal steroids
cholesterol, beta-sitosterol and coprosterol-in the river accounted for 50.8%
80.4% of the total steroids. The ratios of (epicoprostanol+coprostanol) to
(coprostanol+epicoprostanol+cholestanol) of three samples were greater than 0.7,
which indicated the river was contaminated in sampling months. The ratio of
epicoprostanol to coprostanol was less than 0.2 in October, which indicated the
wastewater came from the upstream sewage treatment plant. The ratios of
coprostanol to SigmaSteroids and coprostanol to 24-ethylcoprostanol in January,
March and May were respectively 0.109-0.254 and 6.3-10.3, which indicated that
Laolongdong underground river was mainly polluted by human feces. The ratio of 24
ethylcoprostanol to 24-ethylcholestanol in March (0.86) was less than those in
January (5.4) and May (2.3), which showed the river was polluted more severely in
March than in January and May by poultry dung.
PMID- 29964730
TI - [Distribution Characteristics and Pollution Status of Phthalate Esters in the
Groundwater of Hutuo River Pluvial Fan].
AB - A total of 51 groundwater samples were collected from Hutuo River Pluvial Fan in
September, 2014, and 6 phthalate esters (PAEs) were analyzed by gas
chromatography-mass spectrometry. The distribution characteristics and health
risk assessment were investigated in the present study. The results showed that
the PAEs could not be detected in only one sample site. The concentration of the
six total PAEs ranged between not detectable and 28873.1 ng.L-1, and the PAEs
pollution level of the this research area was higher than other regions reported
in China. There was obvious difference in the characteristics of space
distribution of PAEs constitutes among the three groundwater units. The
concentration of PAEs was sequenced from large to small as follows: Gangnan
reservoir valley fracture pore water unit (G1)> the pore water unit of the top of
Hutuo River Pluvial fan (G2)> the shallow pore water unit of the middle part of
Hutuo River Pluvial fan (G3). The results showed that the DMP was dominant in 23
sample sites among all the 39 samples within the G2 and G3 groundwater units,
while the concentration of PAEs was relatively higher in the other sample points
and the DEHP, DBP were the predominant components, which should be attributed to
the industrial point pollution or the pollution originated from surface runoff
around the sample sites. The health risk of drinking groundwater polluted by PAEs
in the study area was evaluated by the recommended method by US EPA. The non
cancer risk index and the cancer risk index was lower than 1.1*10-2 and 1.2*10-6,
respectively, which was both lower than the risk level recommended by US EPA.
PMID- 29964731
TI - [Impacts of Land Use on the Source of Dissolved Fatty Acids in Epikarst Spring
During Rainy Season].
AB - Fatty acids were quantitatively analyzed by gas chromatography-mass spectrometer
(GC-MS). Dissolved fatty acids were collected from Nanchuan epikarst spring. The
results of BQ, LQ, HQ showed that the average contents of fatty acids were 14870,
12912 and 8801 ng.L-1 from May to July, respectively, and followed the order of
SFA> MUFA> BrFA> PUFA. The monomers with highest content were C16:0 and C18:0.
From May to July, the fatty acid content increased in BQ , LQ, HQ. The
differences in vegetation coverage and bedrock bare rate, as well as the
interaction of the dilution effect and soil transfer increase, led to the changes
in content and the composition of the fatty acids. Based on the molecular
characteristic indices of fatty acids, like H/L, CPIh, TARFA about BQ, LQ, HQ,
and contents of fatty acids which were mainly originated from bacteria,
phytoplankton or terrigenous higher plant, it was indicated that fatty acids were
mainly originated from higher plant in LQ in May, from phytoplankton input in HQ
in July, while from bacteria in the other months in LQ, HQ and from May to July
in BQ.
PMID- 29964732
TI - [Mechanisms of Phosphorus Removal by Modified Zeolites Substrates Coated with Zn
LDHs in Laboratory-scale Vertical-flow Constructed Wetlands].
AB - Zn-Layered double hydroxides (LDHs) were selected to carry out the experiment in
present work based on the previous research results. According to the co
precipitation method, three kinds of different Zn-LDHs (FeZn-LDHs, CoZn-LDHs and
AlZn-LDHs) were synthesized by ZnCl2, FeCl3, AlCl3, and CoCl3 solution in
alkaline conditions and Zn-LDHs were in-situ coated on the surface of natural
zeolites. With the filling of the natural and three kinds of Zn-LDHs modified
zeolites in the columns, test experiments were conducted to study the removal
performance of phosphorus in vertical-flow constructed wetlands. The results
showed that: compared with the natural zeolites, the removal rates of phosphorus
by the three kinds of Zn-modified zeolites were greatly improved, especially for
FeZn-LDHs. Moreover, the maximum adsorption capacity and the desorbed performance
of phosphate were enhanced by the Zn-LDHs coated modification. The adsorption
type of phosphate was converted from physical adsorption to chemical adsorption.
Through reasonable selection of the type of zeolite and the method of
modification, Zn-LDHs modified zeolites could be used to enhance the removal of
nitrogen and phosphorus for the eutrophic water.
PMID- 29964733
TI - [Synergistic Enhancement on Oxidation of Phenol by Fenton Processes by Adding
Ce3+ and Cu2+ Ions].
AB - Synergistic effect of Ce3+ and Cu2+ on the oxidation efficiency of phenol in
different initial pH and H2O2 concentrations by Fenton processes was studied. The
experiment results illustrated that Ce3+/Cu2+/Fe2+/H2O2 system had a wider scope
of application than Fenton process in the aspect of pH and H2O2 concentration.
Phenol was still efficiently degraded by Ce3+/Cu2+/Fe2+/H2O2 at a higher pH
(pH=5.0) and a higher H2O2 concentration (2.0 mmol.L-1). In addition, Cu2+ could
react with quinone-like substrates, the oxidation intermediates of phenol, to
produce Cu+, which could catalyze the decomposition of H2O2 to form.OH, while
Ce3+ could accelerate the formation of quinone-like substrates and facilitate the
cycling of Fe3+ and Fe2+, to enhance the decomposition of H2O2 to form.OH, the
mechanism analysis illuminated the synergy of Ce3+ and Cu2+. The reactive species
in Ce3+/Cu2+/Fe2+/H2O2 system was still proved to be.OH, resulting from the
scavenging experiments by adding different radical scavengers.
PMID- 29964734
TI - [Removal of Humic Acid from Water Using Pt/biochar Electrode Reactor].
AB - A Pt/biochar electrode reactor was developed to remove humic acid in water. The
removal efficiency and characteristics of the reactor were investigated.
Experimental results showed that Pt/biochar electrode reactor obtained 74.58%
removal rate after 300 min reaction under current density of 20 mA.cm-2. The
removal rate was increased by 58.3% comparing with 47.10% removal rate achieved
by Pt/graphite electrode reactor. Electrochemical oxidation and air floating
played the main roles in removal of humic acid from water. The improved removal
efficiency of humic acid in Pt/biochar electrode reactor was attributed to the
fact that the biochar cathode could produce more H2O2 than graphite cathode.
Three-dimensional excitation emission matrix fluorescence spectroscopy and Gel
permeation chromatography measurement revealed that Pt/biochar electrode reactor
had strong oxidation capability to mineralize the low molecular weight humic acid
directly. It suggests that biochar could be use as an innovative cathode material
of electrode reactor for organic pollutants treatment in water.
PMID- 29964735
TI - [Generation of Graphene-titanium Dioxide Nanotubes Catalytic Board and Its
Photocatalysis Capability to Degrade Pentachlorophenol].
AB - Considering that the photocatalysts used in research are generally in powder
form, which increase the difficulty of efficient recycle in practice, this
research focused on the generation of graphene-titanium dioxide nanotubes
catalytic board. Graphene oxide and TiO2 powder were used as precursors; the sol
gel like coating method along with hydrothermal method was adopted to synthesize
the catalytic board. The generated board presented a uniform surface morphology
and in its most regions, the catalyst was loaded in the form of a single layer or
few layers. During the photodegradation process in the eluent system, under solar
irradiation, the removal ratio of the pentachlorophenol (PCP) could reach almost
100% within 30 min, the degradation rate was increased by more than 5 times
compared with the eluent without addition of photocatalyst; while under xenon
lamp, the degradation rate was increased by 10 times. After long-time soaking and
repeated use, the photocatalytic activity of the board did not decrease
obviously, which is suitable for long-term use. The application of the board
could solve the problem of immobilized catalyst and enable catalyst recycling in
subsequence processing.
PMID- 29964736
TI - [Photocatalytic Degradation Kinetics and Mechanism of Monoazo Dye Acid Yellow 17
by UV/TiO2 in Aqueous Solution].
AB - In order to explore the removal methods, transformation, environmental fate,
effect and potential risk of dyes in environmental water, monoazo dye acid yellow
17 (AY17) was selected as model compound to investigate the degradation
possibility in different advance oxidation processes (AOPs), and the degradation
efficiencies followed the order of UV/H2O2 1). The Cd, and Pb
concentrations in paddy soil had strong coefficients of variance (C.V.): 121.05%
and 109.38%, respectively. Soil pH and organic matter (SOM) had significant
correlations with most of the total heavy metals and their available fractions in
soils. The total heavy metals and their available fractions also had strong
correlations, such as total Cd and available Cd in soils. Geostatistics and the
Local Moran's I were used to identify the contaminated hotspots of these five
metals. It was found out that the high soil Cd, Cu, Zn, Pb were located in Daxi
and Zeguo towns, which could be attributed to E-waste dismantling and other
anthropogenic activities. Soil Ni was mainly influenced by the parent material.
The heavy metals in soils may pose a potential threat to local ecosystem and
human health.
PMID- 29964746
TI - [Selenate Adsorption and Desorption in 18 Kinds of Chinese Soil with Their
Physicochemical Properties].
AB - The environmental behavior and bioavailability of selenium (Se) in soils are
greatly affected by its adsorption on soil components, which are largely
discrepant with the different physicochemical properties of soils. 18 kinds of
farmland soils with various physicochemical properties in China were used in
batch adsorption experiments in this study to explore the influencs of soil pH,
amorphous iron, aluminum oxides, organic matter and mechanical composition on the
adsorption of SeO42-. The results showed that the adsorption of SeO42- on 18
soils was an initially fast phase followed by a slow process, during which the
adsorption equilibrium was reached at 24 h. Second-order kinetic
model(R2>0.976)and Freundlich isothermal model(R2>0.842)were the fittest for most
of the adsorption process. SeO42- adsorption capacity of soil was negatively
correlated with soil pH value (P<0.01) and the content of carbonate (P<0.05),
while positively correlated with the content of amorphous iron, aluminum oxides
(P<0.01) and organic matter content (P<0.05). The partition coefficient of solid
to liquid (Kd values) of SeO42- in adsorption process for all the 18 soil types
were very low and without big differences(0.99 L.kg-1-18.18 L.kg-1). The
desorption rates for all tested soils were above 80%, which indicated the
reversibility of SeO42- adsorption in soil. It was inferred from the above that
the low Kd and high desorption rate reflected that selenate was featured by easy
migration and leaching in soil, which should be emphasized in the regional
evaluation and regulation of Se level.
PMID- 29964747
TI - [Adsorption Characteristics of Arsenite on Goethite by Flow Stirring Method].
AB - Adsorption characteristics of arsenite on goethite under the effects of the
solution pH, concentration and temperature were investigated using a flow
stirring dynamic device. The results showed that the adsorption process of
arsenic could be divided into rapid and slow reactions under different
conditions.The maximum of arsenite adsorption fitted by the first order equation
remarkably decreased with increase in the solution pH, for example, 246.9 mg.kg-1
at pH 3.0 and 99.8 mg.kg-1 at pH 7.0, respectively. The rate constant(k')of the
apparent adsorption increased gradually along with the increase of solution pH,
and so the half reaction time(t1/2)was smaller, and the equilibrium time of
arsenic adsorption was shorter. At the same time, the b values of diffusion rate
constant were reduced gradually. With the increase of arsenic concentration, the
amounts of arsenic adsorption and the k' values increased gradually. The maximum
amount of adsorption of arsenic was 96.5 mg.kg-1 and 249.1 mg.kg-1 when the
arsenic concentration was 0.10 mg.L-1 and 1.00 mg.L-1, respectively. Adsorption
constant(Kf)by the Freundlich equation decreased gradually with the extension of
the reaction time and its ability of adsorption was gradually weakened.
Distribution factor(RL)by Langmuir equation was between 0-1, and the adsorption
of arsenic on goethite was accounted for the preferential adsorption. With the
increase of temperature, the maximum amount of adsorption of arsenic was
increased, for example, 241.1 mg.kg-1 at 298 K and 315.6 mg.kg-1 at 313 K,
respectively. And the k' values of the apparent adsorption rate constant
gradually rose in the meantime. The false thermodynamic constants were calculated
using the b values of the diffusion rate by the parabolic diffusion equation. The
reaction activation energy(Ea*)of Arsenic adsorption was 14.60 kJ.mol-1. The
change of arsenic diffusion activation enthalpy(DeltaHtheta)decreased with the
increase of temperature, and DeltaHtheta was positive in values and on behalf of
the endothermic process. So the rising temperature was beneficial to the
diffusion of arsenic. DeltaGtheta of activation free energy was increased as the
temperatures rose, and helpful to accelerate the diffusion process. Entropy of
activation(DeltaStheta)was negative in all cases, suggesting that the system
could improve its degree of order.
PMID- 29964748
TI - [Preparation of Poly-hydroxy-aluminum Pillared Diatomite and Characteristics of
Cu2+, Zn2+ Adsorption on the Pillar in Aqueous Solutions].
AB - As an alternative solution to the limitations in adsorption properties of natural
diatomite caused by its physicochemical structure defects and modification
effects to diatomite using conventional physical/chemical methods, the diatomite
was pillared using poly-hydroxy-aluminum to improve its adsorption properties.
The change in physicochemical characteristics of the diatomite before and after
pillaring were analyzed by Scanning Electron Microscope (SEM), Fourier Transform
Infrared (FTIR) and X-ray Diffraction (XRD). The difference in surface properties
of diatomite and its adsorption characteristics of Cu2+, Zn2+ before and after
pillaring were analyzed at the same time. The obtained results showed that the
optimal conditions for diatomite pillaring were 2.2 of the [OH-]/[Al3+] molar
ratio, 1.8 mol.L-1 of potassium chloride, 10 mmol.g-1 of the Al/diatomite ratio,
60C of the pillaring temperature, 24 h of the pillaring time, 200C of the aging
temperature, and 0.5 h of the aging time. After pillaring, the poly-hydroxy
aluminum was successfully exchanged into the diatom shell, forming available
pillars, which increased channel spacing, expanded adsorption reaction interface,
increased the number of microporous surface hydroxy groups and enhanced the
microporous surface activity. The Cu2+, Zn2+ adsorption data obtained both before
and after pillaring well fitted the Langmuir isotherm model and the pseudo-second
order kinetics model. After pillaring, the adsorption capacity of Cu2+, Zn2+ onto
diatomite reached 7.491, 11.312 mg.g-1, with an increasing percentage of 32.9%,
33.3% respectively, the diatomite adsorption capacity got great improvement.
PMID- 29964749
TI - [Preparation and NH4+-N Removal Performance of a Novel Filter Substrate Made from
Sludges].
AB - A novel absorbent was prepared by high-temperature calcination using waterworks
terminal aluminum coagulation sludge as a raw material. This study discussed
ammonia nitrogen adsorption performance of the adsorbent by static adsorption
test, mainly investigated the influences of different initial pH, contact time
and temperatures on the ammonia adsorption effect, and also analyzed the
adsorption isotherms, kinetic and thermodynamic properties of adsorbent on the
ammonia nitrogen. Experimental results showed that the adsorbent had a better
effect for ammonia removal under neutral conditions; the adsorption process was
basically balanced within 6 h, and it followed the pseudo second-order model.
Langmuir adsorption model could be better fitted for the adsorption of ammonia
adsorbent; the thermodynamic parameters indicated that the adsorption process of
ceramic adsorbents on NH4+-N was a kind of spontaneous, endothermic reaction
(DeltaGtheta <0, DeltaHtheta >0), and it was found to be a physical adsorption
based on the average adsorption energy. Thus, treating ammonia wastewater by
coagulation sludge has a good prospect.
PMID- 29964750
TI - [Preparation of Nanocomposite Hydrogel and Its Adsorption of Heavy Metal Ions].
AB - An acylamino and hydroxyl functionalized hydrogel [p(HMAm/HEA)] was newly
prepared by the 60 Co-gamma-induced polymerization of N-hydroxymethyl acrylamide
(HMAm) and 2-hydroxyethyl acrylate (HEA). Then the copolymer p(HMAm/HEA) hydrogel
was utilized for in situ nanosized hydrous manganese dioxide (HMO) loading to
prepare nanocomposite hydrogel HMO-p(HMAm/HEA) for Pb2+ and Cu2+ removal. The
nanocomposite hydrogel was characterized by SEM, TEM and FTIR, showing that
p(HMAm/HEA) hydrogel was indeed a copolymer of HMAm and HEA monomers, and the
loading of HMO nanoparticles onto p(HMAm/HEA) was successful. Various influencing
parameters on heavy metal ions removal by HMO-p(HMAm/HEA), such as initial pH,
temperature, initial heavy metal concentration, contact time and competing Ca2+
and Na+, were estimated. The results showed that the adsorption process was
temperature-independent, pH-sensitive, Langmuir monolayer adsorption and followed
a pseudo-second-order rate equation. The presence of high concentrations of
competing Ca2+ and Na+ had no significant effect on the adsorption process. The
XPS spectra analyses further indicated that Pb2+ and Cu2+ were adsorbed via the
ion exchange of -OH groups. Moreover, HMO-p(HMAm/HEA) could be regenerated by
0.05 mol.L-1 of HCl, and obtained excellent repeated use.
PMID- 29964751
TI - [Prediction of PAHs Bioavailability in Spiked Soil by Composite Extraction with
Hydroxypropyl-beta-cyclodextrin and Rhamnolipid].
AB - In this study, composite extraction of hydroxypropyl-beta-cyclodextrin (HPCD)
with rhamnolipid (RL) was selected to assess the bioavailability of polycyclic
aromatic hydrocarbons (PAHs) to earthworms in red soil from Hainan, China, spiked
with phenanthrene (Phe), pyrene (Pyr) and benzo (a) pyrene (BaP). The results
showed that when RL was more than the critical micelle concentration, apparent
solubility of PAHs increased due to micellar solubilization of RL. So more PAHs
were desorbed from solid phase of soil. Real biological experiments showed that
there was a good linear relationship between earthworm-accumulated PAHs and
HPCD/RL-extracted PAHs (R2=0.98, n=15). However, earthworm-accumulated PAHs was
2.04 times higher than HPCD-extracted PAHs, but only 1.15 times higher than
HPCD/RL-extracted PAHs. This indicated that HPCD/RL was more actual and reliable
than HPCD in the assessment of PAHs bioavailability to earthworms. Therefore, the
addition of RL, to some extent, enhanced the prediction ability of HPCD in PAHs
bioavailability, which might provide a new direction and implications in risk
assessment and bioremediation of organic contaminants.
PMID- 29964752
TI - [Biological Effects of ZnO Nanoparticles as Influenced by Arbuscular Mycorrhizal
Inoculation and Phosphorus Fertilization].
AB - ZnO nanoparticles (NPs) are widely used in many applications, such as plastics,
ceramics, glass, cement, rubber, lubricants, paints, pigments, batteries, fire
retardants, catalysts, and anti-microbial agents. They directly or indirectly
enter aquatic and terrestrial environments through application, accidental
release, contaminated soil/sediments, or atmospheric fallouts. When present in
excess, ZnO NPs can induce phytotoxicity and reduce plant growth and yields. ZnO
NPs can also cause Zn accumulation in edible parts of food crops, and then
subsequently enter human bodies and pose a significant health risk. Arbuscular
mycorrhizae are ubiquitous symbiotic associations in nature formed between
arbuscular mycorrhizal (AM) fungi and most higher plants in terrestrial
ecosystems. In addition to their well-known contribution to plant nutrient
acquisition and growth, AM fungi can improve plant tolerance to various
environmental stresses, but mycorrhizal effects vary with environmental
conditions such as phosphorus status in both soil and plants. AM fungi have been
shown to alleviate the negative effects of ZnO NPs and zinc accumulation in
plants, however, the role of phosphorus fertilization has been neglected. A
greenhouse pot culture experiment was conducted using maize as the test plant
inoculated with or without AM fungus Funneliformis mosseae. Four levels of
phosphorus (0, 20, 50 or 100 mg.kg-1) and two levels of ZnO NPs (0 or 500 mg.kg
1) were applied to pots. Shoots and roots were harvested separately after two
months of growth. Mycorrhizal infection, plant biomass, P and Zn concentrations
and uptake in plants, and soil DTPA-extractable zinc and pH were determined. The
results showed that ZnO NPs did not significantly affect the growth of maize, but
inhibited root mycorrhizal infection and plant phosphorus uptake, and led to the
accumulation of zinc in plants. ZnO NPs and high phosphorus supply decreased root
mycorrhizal infection, but AM inoculation significantly promoted plant growth
under all phosphorus supply levels. Phosphorus application and AM inoculation
increased soil pH, but reduced the bioavailability of Zn derived from ZnO NPs,
decreased the translocation and accumulation of zinc in maize shoots, and thus
produced beneficial effects on plants. In general, AM inoculation showed positive
mycorrhizal effect, especially under low phosphorus conditions and addition of
ZnO NPs. Our results showed for the first time that both AM fungi and phosphate
fertilizer could help to mitigate soil pollution and the ecological and health
risks posed by ZnO NPs.
PMID- 29964753
TI - [Difference of Species Sensitivities for Aquatic Life Criteria in China and the
USA].
AB - Recently, China has commenced water quality criteria (WQC) research using the
species sensitivity distribution (SSD) method. However, it is difficult to obtain
sufficient toxicity data on native species for thousands of contaminants. In this
study, the feasibility of deriving aquatic life criteria using toxicity data from
non-native species was analyzed (taking the USA as an example). Firstly, 10
pollutants [As(III), Cr(VI), Hg, Cu, Pb, Zn, nitrobenzene, parathion,
chlorpyrifos, tributyltin] with plenty of toxicity data (at least 3 Phyla and 8
Families) both in China and the USA were selected based on the recommended
aquatic life criteria of 58 pollutants by the US EPA. Secondly, the two-sample
Kolmogorov-Smirnov (K-S) test and comparison method of important points of HC5
and HC50 (hazardous concentrations for 5% of the species and 50% of the species)
were used to determine the difference of species sensitivity between China and
the USA. The result of two-sample K-S test showed that the difference of species
sensitivity to Cu, chlorpyrifos and tributyltin between the two countries was
significant (P<0.05). Additionally, there were significant differences for HC5
values [Cr(VI), chlorpyrifos] between the two countries, as well as the HC50
(chlorpyrifos). As a result, there were significant differences for the species
sensitivity to some pollutants [Cr(VI), chlorpyrifos, etc.] between China and the
USA. Therefore, in this situation, "over-protection" or "non-protection" may
happen when using the criteria values or the toxicity data of American species
directly to protect the Chinese native species.
PMID- 29964754
TI - [Effects of Low-level Nutrition and Trace Antibiotics on the Fitness Cost of
Plasmids Bearing Antibiotic Resistance].
AB - The effects of nutrition and antibiotic level on fitness costs of plasmid
containing antibiotic resistance in drinking water system were investigated in
this study. Three plasmids harboring different antibiotic resistances, i.e.
pACYC184, RP4, and PBR322, were selected. It was found that the antibiotic
resistance imposed cost on the fitness of all plasmids at different nutrition
levels, which was universal. Moreover, the fitness costs were larger at lower
nutrition levels. Besides, the fitness costs of plasmid bearing antibiotic
resistance were also affected by trace antibiotics. In this study, when exposed
to antibiotics (lower than 50% MIC), the fitness costs of plasmid imposed to the
bacteria were more apparent than the injury or inhibition effect by antibiotics.
The plasmids were unstable. Therefore, it was inferred that the plasmid
containing antibiotic resistance imposed large fitness costs on bacteria in
drinking water system (with low-level nutrition and ng.L-1 level antibiotic), and
it was not stable. Thus, the risk of plasmid bearing antibiotic resistance
transmission and spread in drinking water system was low.
PMID- 29964755
TI - [Effect of Different Nitrogen Rates on the Nitrification Potential and Abundance
of Ammonia-oxidizer in Intercropping Maize Soils].
AB - The objectives of this study were to explore the effects of different nitrogen
rates on the nitrification potential in intercropping maize soils. The experiment
included two plantation types (maize monocropping and intercropping maize and
potato) and four nitrogen levels (N0: no fertilizer treatment, N1: 1/2
conventional fertilizer treatment, N2: conventional fertilizer treatment, N3: 3/2
conventional fertilizer treatment). Abundance of AOA and AOB was analyzed with
real-time quantitative PCR (Q-PCR) and soil properties were also measured.
Results of this study suggested that the PNF of soils, the abundance of AOA and
AOB were increased with increasing N fertilization in conventional fertilizer
range, and there was no significant difference between N2 and N3 treatments. The
influences of intercropping on PNF, AOA and AOB were associated with N
application rates and crop growth period, as well as the benefits of ammonia
oxidizer and nitrification of intercropping on N1 level. Fertilization was
obviously the main driving force of the PNF, correlation analysis indicated that
water content was the main environmental factor affecting the nitrification
potential. Nitrification potential in maize and potato intercropping soils
exhibited significant positive correlations with AOA and AOB amoA gene abundance.
Maize and potato intercropping could decrease the abundance of AOA and AOB, but
it resulted in dominance of AOB among nitrification bacteria in these soils. In
conclusion, N fertilizer and intercropping could affect both soil nitrogen
internal cycling process and the abundance of AOA and AOB, which further affected
soil environmental quality.
PMID- 29964756
TI - [Temporal and Spatial Variation of Haze Pollution over China from 1960 to 2013].
AB - Based on haze observation and related meteorological data from the surface
weather stations in China during 1960-2013, we analyzed the variation of haze
days and its relationship to meteorological elements using climatic linear-trend
estimation, cluster analysis, cumulative departure and the Mann-Kendall test. The
results showed that the haze events occurred mainly in mid-eastern and southern
China, especially in Beijing, central and southern areas of Shanxi, Henan, the
Yangtze River Delta and Pearl River Delta areas. At the same time, the haze days
were less frequently observed in western and northeastern China. The occurrence
of haze days was increasing in the past 54 years, which was consistent with the
total energy consumption in China. While the emission of air pollutant could be
an important factor of haze increase, the adverse weather conditions also played
a role. The correlation coefficients of precipitation, average wind speed,
sunshine duration and relative humidity with haze days were -0.653, -0.635,
0.462 and -0.699, respectively, which all exceeded the 99.9% significance.
Cluster analysis showed that haze days of stations with very significant
increase, significant increase and obvious increase have accelerated in recent
years, and the trend of cumulative variance type was fall-flat-rise. Haze days of
slight rise station increased from 1960s to the late1970s and after 2000, of
which cumulative variance type was multi wobbled. Moreover, Haze days of slight
fall and obvious fall stations increased from 1960s to 1970s, and their
cumulative variance types were rise-gently-fall. Furthermore, haze days showed
mutation from more to less during 1992 to 1993.
PMID- 29964757
TI - [Concentrations and Size Distributions of Water-soluble Inorganic Ions in Aerosol
Particles in Taiyuan, Shanxi].
AB - Size-resolved filter samples were collected in Taiyuan every other week from June
2012 to May 2014. The mass concentrations of water-soluble ions (Na+, NH4+, K+,
Mg2+, Ca2+, F-, Cl-, NO3- and SO42-) were measured by ion chromatography. The
results showed that the total concentrations of measured water-soluble ions were
(15.39+/-9.91), (21.10+/-15.49) and (36.34+/-18.51) MUg.m-3 in PM1.1, PM2.1 and
PM9, respectively. In PM1.1 and PM2.1, secondary water-soluble ions (SO42-, NO3-
and NH4+) comprised 87.59% and 86.30% of all water-soluble ions, respectively,
while in PM9, SO42- and Ca2+ comprised 32.78% and 28.54% of all water-soluble
ions, respectively. SO42- and NH4+ had higher concentrations in winter and
summer, and lower in spring and autumn. NO3-, K+and Cl- presented similar
seasonal variation with a descending order of winter >autumn >spring >summer, and
Ca2+ and Mg2+ followed the sequence of spring >winter >autumn >summer. SO42- and
NH4+ showed a unimodal size distribution and the peak in the fine mode shifted
from 0.43-0.65 MUm in spring and autumn to 0.65-1.1 MUm in summer. NO3- showed a
bimodal size distribution. NO3- and NH4+ were dominated by the fine mode peaking
at 0.43-2.1 MUm in winter, and NO3- was dominated by the coarse mode peaking at
4.7-5.8 MUm in summer. K+, Na+and Cl- also showed a bimodal size distribution
with the fine mode at 0.43-1.1 MUm and the coarse mode at 4.7-5.8 MUm. Ca2+, Mg2+
and F- were unimodal with the peak in the coarse mode of 4.7-5.8 MUm. On heavily
polluted days, the mass concentrations of secondary water-soluble ions and Cl-
accumulated, and secondary water-soluble ions were unimodal with the peak in the
fine mode of 1.1-2.1 MUm. However, on clear days, secondary water-soluble ions
showed a bimodal size distribution with the fine mode at 0.43-0.65 MUm and the
coarse mode at 4.7-5.8 MUm. The peak of secondary water-soluble ions in the fine
mode shifted. PCA analysis showed that the sources of water-soluble ions were
dominated by the secondary formation, coal combustion, industrial emission,
biomass burning, and soil particles or falling dust.
PMID- 29964758
TI - [Characteristics of the Size Distribution of Water Soluble Inorganic Ions During
a Typical Haze Pollution in the Autumn in Shijiazhuang].
AB - To characterize the size distribution of water soluble inorganic ions (WSII) in
haze days, particle samples were collected by an Andersen cascade impactor in
Shijiazhuang from October 15 to November 14 in 2013, and the concentrations of
eight kinds of WSII (Na+, NH4+, K+, Mg2+, Ca2+, Cl-, NO3-and SO42-) during a
typical haze episode were analyzed by ion chromatography. Sources and formation
mechanism of WSII were analyzed based on their size distributions. The results
showed that Shijiazhuang suffers serious air pollution during the autumn season.
The daily average concentrations of PM10and PM2.5were (361.2+/-138.7) MUg.m-3 and
(175.6+/-87.2) MUg.m-3 and the daily average concentration of PM2.5was 2.3 times
as high as the national secondary standard. The total water soluble inorganic ion
concentrations (TWSII) in clean days, light haze days and heavy haze days
were(64.4+/-4.6)MUg.m-3, (109.9+/-22.0)MUg.m-3 and (212.9+/-50.1) MUg.m-3
respectively. In addition, the ratio of secondary inorganic ions (SNA:SO42-, NO3-
and NH4+) in TWSII increased from 44.9% to 77.6% as changed from clean days to
the heavy haze days, suggesting the evolution of haze episodes mainly originated
from the formation and accumulation of SNA. The size distributions of SO42-, NO3-
and NH4+ were bimodal in clean days, peaking at 0.43 -0.65 MUm and 4.7-5.8 MUm,
respectively, which changed to unimodal distribution in both the light and heavy
haze days, peaking at 0.65-1.1 MUm. Owing to high humidity during the heavy haze
days, the aqueous phase reactions of SO42- and NO3- were likely promoted, which
led to the transformation of condensation mode in clean days to the droplet mode
in haze days. The size distributions of Na+, Mg2+ and Ca2+ were different with
that of SNA, which showed a coarse mode peaking at 4.7-5.8 MUm both in clean and
haze days, whereas K+and Cl- showed a bimodal distribution both in clean and haze
days, although the modal size was different in clean and haze days.
PMID- 29964759
TI - [Variation of Size Distribution and the Influencing Factors of Aerosol in
Northern Suburbs of Nanjing].
AB - The size distribution of particulate was analyzed by the FA-3 9 stage sampler in
Northern-suburb of Nanjing from January to November in 2014. First, the
monitoring result from FA-3 was compared with the results of the same period
obtained from a medium flow size grading sampler (KC-120H) and online monitoring
instrument of the Environmental Protection Agency. The data correlation
coefficients were all greater than 0.95. The fine particle concentration from FA
3 was lower by 13.9% and 16.6%, while PM10 concentration was higher by 15.2% and
13.3% respectively. However, the deviations were in the acceptable range of
atmospheric sampling which could indicate the accurate classification and
sampling of particulate for FA-3. Particulate pollution in Northern-suburb
Nanjing was serous in which the annual average concentrations of PM1.1, PM2.1 and
PM10 were(65.6+/-37.6), (91.0+/-54.7) and (168.0+/-87.0) MUg.m-3 respectively;
fine particles dominated and most of them had a diameter of less than 1.1 MUm.
Particle size distribution was bimodal with peaks at 0.43-0.65 and 9-10 MUm; the
median diameter was 1.83 MUm which was in the accumulation mode. In winter, the
concentration of fine particle size was higher and in spring the coarse particle
size was higher; in summer, the fine particle size concentration was not
significantly reduced but coarse particle size was obviously lower than those in
other seasons. The differences of particle size distribution in day and at night
were very small in coarse segment and in fine segment, the nocturnal
concentrations were mostly higher than diurnal concentrations. The precipitation
had cleaning effect for each size range of particulate except in summer and the
effect was more distinct in fine particle size. In haze days, with the
aggravation of haze level, the particle concentration in the diameter range of
0.43-2.1 MUm increased gradually while in this segment the particle concentration
was significantly negatively correlated with visibility. Using relative humidity
of 70% as the demarcation, the particle size distribution changed
significantly:when humidity was greater than 70%, mass concentration of particle
with a diameter of less than 0.43 MUm reduced significantly but that with
diameter range of 0.43-2.1 MUm increased obviously which should be related to the
particle hygroscopic growth. The air mass sources could be divided into four
categories in northern-suburb of Nanjing. Air mass from the northwest with rapid
transport velocity was the cleanest in which the fine particle size concentration
was significantly lower than those in other directions; the air mass from local
and surrounding was the most severely polluted with high concentrations in both
fine and coarse segment, its transmission distance was short and wind speed was
small which contributed greatly to air pollution of Nanjing with probability of
occurrence of pollution reaching 73.9%.
PMID- 29964760
TI - [Characteristics of Black Carbon Aerosol and Influencing Factors in Northern
Suburbs of Nanjing].
AB - Based on the hourly averaged data of black carbon(BC) aerosol, PM2.5, gaseous
pollutants, and meteorological data in the northern suburb of Nanjing from
January to October 2015, characteristics and influencing factors of BC
concentration variation were analyzed. The mean concentration of BC was found to
be (2524+/-1754) ng.m-3 during the observation period. BC concentrations in
Nanjing showed strong seasonality, the highest mean concentration of BC occurred
during winter reaching (3468+/-2455) ng.m-3, and the lowest mean BC concentration
was found during spring being (2142+/-1240) ng.m-3; a distinct diurnal variation
of BC with two high peaks occurred, one in the morning during 07:00 to 08:00 and
the other in late evening during 21:00 to 22:00 local time. The strong
correlation between BC and NOx indicated a greater impact of vehicle emissions on
BC concentration, while a lower rate of DeltaBC/DeltaCO was found in the northern
suburb of Nanjing, suggesting that biomass burning emission might be another
important source of BC in here. BC concentration increased with decreasing wind
speed. BC concentration lower than 2000 ng.m-3 mainly occurred in westerly wind
and adjacent wind in all seasons, whereas BC concentration higher than 6000 ng.m
3 more frequently appeared in easterly winds in autumn and winter. BC
concentration was higher in hazy and heavy hazy weather, which were 2 and 2.3
times as large as that in non-hazy weather, respectively.
PMID- 29964761
TI - [Characteristics of Speciated Atmospheric Mercury in Chongming Island, Shanghai].
AB - Continuous monitoring of gaseous elemental mercury (GEM), reactive gaseous
mercury (RGM) and particulate mercury (PBM) was conducted in the Dongtan wetland
park in Chongming Island, Shanghai from March 2014 to February 2015. The average
concentrations of GEM, RGM, and PBM were (2.75+/-1.13) ng.m-3, (13.39+/-15.95)
pg.m-3, and (21.89+/-40.42) pg.m-3, respectively, higher than the background
concentrations of Northern Hemisphere. The atmospheric mercury showed obvious
seasonal variations, with the highest seasonal average GEM concentration in
summer (3.65 ng.m-3), which was mainly influenced by natural sources, while lower
GEM concentrations appeared in autumn and winter influenced mainly by
anthropogenic sources. The concentration of RGM was highest in spring and lowest
in winter, mainly influenced by the wind direction, while PBM showed higher
concentrations in autumn and winter, when heavy fine particulate pollution
episodes occurred frequently. The concentrations of GEM and PBM were generally
elevated in nighttime and lower in daytime caused by the mixing condition of the
air masses. Most of the high RGM concentration values occurred in the afternoon
of all seasons due to the higher atmospheric oxidation. The concentrations of GEM
and PBM were higher in the west wind due to the emission from anthropogenic
sources in Shanghai, Jiangsu, etc. The RGM concentration in southeast wind was
obviously higher than those in other wind directions. The RGM was mainly from the
anthropogenic sources, and the smaller wind in the southeast direction was
against the dispersion of RGM.
PMID- 29964763
TI - [Variation Characteristics and Sources Analysis of Atmospheric Volatile Organic
Compounds in Changbai Mountain Station].
AB - Volatile organic compounds (VOCs) play very important roles in the formation of
ozone and secondary organic aerosols. The concentrations, compositions, and
seasonal variation of VOCs were measured in 2012 at Changbai Mountain Forest
Ecosystem Research Station, a remote station in Northeast China. Weekly samples
were collected in the Changbai Mountain area and analyzed via gas chromatography
mass spectrometry. The results showed that the annual mean concentration of total
VOCs (TVOCs) was 10.7*10-9+/-6.2*10-9. Halohydrocarbon was the most abundant
component, accounting for 37% of the total VOCs, followed by alkanes and
aromatics, accounting for 33% and 15% respectively, and alkenes accounted for
15%. The seasonal variation of TVOCs in this area was obvious, and the order was
spring >autumn >summer >winter. TVOCs concentration in spring was very
significantly higher than those in any other season (P<0.05). The principal
component analysis (PCA) was used to identify the sources of the VOCs. Five
sources were resolved by the PCA, including traffic sources, LPG,biogenic
sources, combustion sources, industrial sources and regional transportation. The
HYSPLIT-4.0 model was used to analyze the effect of pollutant transport, and the
results indicated that the transport of pollutants from southwest had a
significant effect on the increase of VOCs concentration.
PMID- 29964762
TI - [Total Gaseous Mercury and Mercury Emission from Natural Surface at One Typical
Agricultural Region in Three Gorges Reservoir].
AB - In situ measurement of total gaseous mercury (TGM) and mercury exchange fluxes
between soil with different utilization patterns and atmosphere was conducted at
one typical agricultural region in Three Gorges Reservoir. The TGM concentration
ranged from 2.67 to 75.5 ng.m-3 with the average of (6.26+/-8.11) ng.m-3, higher
than the global background value. An obvious seasonal variation of TGM was
observed, and the TGM values in spring and winter were significantly higher than
those in summer and autumn. It was found that the mercury fluxes varied from
different landscapes with the emission fluxes at three land use types following
the trend:rainfed cropland >paddy field >forest land. Seasonal variations of
mercury emission were obvious with highest fluxes in summer and lowest in winter,
while the highest daily mercury emission fluxes appeared at midday. Mercury
emission fluxes in our study region were mainly controlled by air and soil
temperature, humidity, light and ultraviolet, and the air temperature and
ultraviolet were regarded as the main factors. The influence of Hg level in soil
on Hg emission was not obvious in the presence of environmental factors and
agricultural activity.
PMID- 29964764
TI - [Characterization of Particle Size Distributions of the No-organized Lead
Emission for a Lead and Zinc Smelter].
AB - Using TH 880-F type dust tester and low pressure impactor (LPI), the size
segregated atmospheric particulates were collected, the particle size
distribution characteristics and the content of lead were analyzed in the
unorganized emission area (1 and 2) from the Blast and ISA furnaces within a lead
zinc smelter in Yunnan province. The results showed that lead in PM2.5(fine
particulate matter, particle size <2.5 MUm) accounted for 66.6% and 43.1% of
PM10(particulate matter, particle size <10 MUm) and TSP(total suspended particle,
particle size<100 MUm) in unorganized emission area 1, and the corresponding
proportions in the unorganized emission area 2 were 54.1% and 38.7%, all these
showed that the lead pollution mainly existed in small size particles. There was
a close correlation between the lead content in the unorganized emission
particulate matter and the wind direction and wind speed in the surface
meteorological data, followed by the wind energy density. In lead smelting area,
the correlation of lead content in the unorganized emission particulate matter
with the wind direction and wind speed was the highest, followed by the wind
energy density w. In the slag field, the correlation between lead content in the
unorganized emission particulate matter and the vertical distribution of the
temperature (gamma) of the boundary layer was the highest, followed by the
component u and v, and then the wind energy density w.
PMID- 29964765
TI - [Hydrochemical Characteristics and Sources of Ions in Precipitation at the East
Qilian Mountains].
AB - Precipitation of the northwest China is different from that in other regions of
China. The vapor reaches this region after long distance transportation with
little precipitation, and the ratio of precipitation variation is large.
Wushaoling at the east Qilian Mountains is an important divided line of climate
in China. The east region of it is affected by South Asia and East Asia monsoon,
while the west region of it is influenced by Westerly circulation. So ion
combinations in precipitation are complex for the trajectories of water vapor
transportation, the natural environments and the development levels of social and
economy in different regions. Precipitation samples were collected at Heisongyi
located at the east Qilian Mountains. Hydrochemical characteristics and sources
of ions were analyzed by factor analysis, Enrichment factor analysis and back
trajectory analysis. EC values in precipitation ranged from 29.20 to 892.00
MUS.cm-1, which were controlled by alkaline element. The precipitation was weak
alkaline with pH values ranging from 7.02 to 8.89. EC values in precipitation
were higher in autumn and winter than in spring and summer, opposite to pH
values. The type of precipitation was SO42--Ca2+ for the cation concentrations
following the order of Ca2+ >Mg2+ >Na+ >NH4+ >K+ and the anion concentrations
following the order of SO42- >Cl- >NO3-. The concentrations of K+, Mg2+, Ca2+,
NH4+, Cl-, NO3- and SO42- were the highest in autumn, but the peak value of Na+
concentration appeared in winter. As a whole, ion concentrations were higher in
autumn and winter than in spring and summer. Enrichment factor indicated that
Na+and Cl- mainly came from marine source but Na+ partly originated from crust
source in winter and Cl- partly originated from anthropogenic source in winter,
and that K+, Mg2+ and Ca2+ mainly came from crust source except that Mg2+ partly
originated from anthropogenic source in winter, and that NO3- and SO42- mainly
came from anthropogenic source. The trajectories of water vapor transportation
from directions of northwest, north, north with southeast, northwest with
southeast, northwest with southwest, northwest with north and southeast were ion
original sources in precipitation, and the major trajectory came from northwest
direction. Among these trajectories of water vapor transportation, that from
northwest, north and north with southeast appeared in each season, but that from
northwest with southeast appeared in spring and summer, that from northwest with
southwest and northwest and north with southeast appeared in summer. Though ions
originated from marine transport by Westerly and monsoon, from crust provided by
desert and Gobi in central Asia, Xingjiang and Mongolian plateau, and from
humanity activity related to cities pollution and industrial and agriculture
production of oasis at all trajectories, the concentrations of ions in
precipitation were effected by the strong and weak variations of different
weather systems.
PMID- 29964766
TI - [Pollution Characteristics and Ecological Risk Assessment of Vanadium in
Sediments of the Three Gorges Reservoir (Chongqing-Yichang Section)].
AB - In order to investigate the pollution characteristics of vanadium in sediments of
the Three Gorges Reservoir (TGR), 67 sediment samples were collected from the
section between Chongqing to Yichang in TGR. The concentration and chemical
speciation of vanadium were measured and the spatial distribution of vanadium was
discussed. Current pollution level of vanadium in TGR sediments was assessed by
index of geoaccumulation and Hakanson ecological risk index. The results showed
that:1the range of vanadium concentrations in TGR was 89.4-175.2 mg.kg-1 and the
average concentration was 123.7 mg.kg-1, which was slightly higher than the
background value in sediments of Yangtze River. 2the spatial distribution of
vanadium in TGR sediments showed that vanadium concentrations in the mainstream
of TGR were higher than those in tributaries and the vanadium contents in the
sediments in downstream were higher than those in upstream in term of the
mainstream of TGR. 3highest vanadium concentration was found in the sediment in a
developed county, indicating that this high level of vanadium concentration was
attributed to anthropogenic input. 4chemical forms of vanadium in sediments were
mainly in residual state (80%-89%, mass fraction), which had a significant
positive correlation with total concentrations in sediments. 5vanadium
contamination degree and potential environmental risk in TGR sediments were weak.
PMID- 29964767
TI - [Distributions of Arsenic Species in Different Eutrophic Waters of Lake Taihu and
Their Relations to Environmental Factors].
AB - A detailed field survey of arsenic species and water quality parameters was
conducted in different eutrophicated regions of Lake Taihu (Zhushan Bay, Meiliang
Bay, Gonghu Bay and Southern Taihu) in summer and winter. Furthermore, spatial
and seasonal distributions of arsenic species and their relations to water
quality parameters were investigated with multivariate analysis techniques.
Higher average contents of total arsenic (TAs), arsenate[As(V)], arsenite[
As(III)] and methylarsenicals [sum of monomethylarsenic acid (MMA) and
dimethylarsenic acid (DMA)] were observed in northern regions (including Zhushan
Bay, Meiliang Bay, and Gonghu Bay) (TAs:2.58-3.34 MUg.L-1, As(V):1.37-2.34 MUg.L
1, As(III):0.53-0.64 MUg.L-1, methylarsenicals:0.16-0.36 MUg.L-1), compared to
those in Southern Taihu (1.73, 1.10, 0.31, 0.10 MUg.L-1). The results exhibited
obvious spatial characteristics of arsenic species in the surface water of Lake
Taihu. Besides, average values of TAs, As(V), As(III) and methylarsenicals in
summer were 3.40, 2.06, 0.73 and 0.25 MUg.L-1, respectively, higher than those in
winter (1.78, 1.10, 0.30, 0.17 MUg.L-1), reflecting significant seasonal
characteristics of arsenic distribution. Factor analysis revealed the significant
relationships of TAs and As(V) with several water quality parameters, which
suggested that spatial and seasonal distributions of TAs and As(V) in Lake Taihu
were affected by external pollution and internal arsenic release from sediments.
Redundancy analysis further indicated significant effects of total phosphorus
(TP) and total iron (TFe) on the distributions of TAs and As(V). At the mean
time, the above statistical analyses exhibited that As(III) and methylarsenicals
were positively correlated with chlorophyll-a (Chl-a). A large amount of
microalgae could accumulate As(V) and transform it more strongly to As(III) and
methylarsenicals in eutrophic regions when compared to mesotrophic
region,especially in summer, reflecting the regulation of microalgae on arsenic
biotransformation.
PMID- 29964768
TI - [Spatial, Temporal Distribution Characteristics and Potential Risk of PPCPs in
Surface Sediments from Taihu Lake].
AB - Fourteen sediment samples from 15 river estuaries and six sediments from 6
drinking water resource were collected from Taihu Lake. Nine pharmaceutical and
personal care products(PPCPs) in the sediments samples were measured by using the
HPLC-MS/MS technique. The ranges of geometric mean values were 1.60-129 ng.g-1
and 1.36-22.0 ng.g-1, respectively. Caffeine was the dominant pollutant in
fourteen sediments near the river estuary, the content of which covered 52% of
amounts of 9 PPCPs. Lincomycin, trimethoprime, azithromycin, sulfamethoxazole and
tylosin were the dominant pollutants in six sediments near the drinking water
resource, the contents of which covered 79% of amounts 9 PPCPs. From the point of
spatial distribution, the results of PPCPs in Zhushan bay and East of Yixing in
the northwest and west of Taihu Lake showed higher concentration than those in
other sample sites. From the composition, the origin of PPCPs was different.
Municipal sewage, stock farming and aquaculture were the main sources of PPCPs in
Taihu Lake. Pharmaceuticals of human use showed the dominant pollution in
fourteen sediments near the river estuary and drugs of veterinary use showed the
dominant pollution in six sediments near the water resource. The concentrations
of PPCPs in fourteen sediments of river mouth showed high level. It suggested
that PPCPs pollutants were discharged to Taihu Lake continuously. Further risk
assessment results showed that the overall risk was not high except for some
PPCPs compounds. The RQ exceeded 1 for acetaminophen, azithromycin and
sulfamethoxazole in the surface sediments of 15 river estuaries and 6 water
resources, which showed high risk. The RQ was between 0.01 to 0.1 for carbazepine
in the surface sediments of 15 river estuaries and 6 water resources, which
showed medium risk. The RQ was below 0.01 for caffeine, lincomycin, trimethoprim,
diltiazem and tylosin in the sediments of 15 river estuaries and 6 water
resources, which showed low risk.
PMID- 29964769
TI - [Distribution Characteristics and Source Identification of Organochlorine
Pesticides in the Karst Groundwater System].
AB - Chongqing Laolongdong and Qingmuguan karst underground rivers were selected as
the research objects, and 21 kinds of OCPs in those two underground rivers were
analyzed by gas chromatography (GC-MUECD). The results showed that, o,p'-DDE,p,p'
DDE, o,p'-DDD were not detected in Nanshan and Qingmuguan underground rivers;
o,p'-DDT and dieldrin were not detected in Qingmugang; but the detection rate of
the rest of the OCPs in those two underground rivers was as high as 100%. HCHs
and ALDs were the most dominant compounds in Laolongdong underground river,
whereas HCHs and methoxychlor were the most dominant compounds in Qingmuguan. The
concentration range of total OCPs in Qingmuguan was 145-278 ng.L-1 with a mean
value of 213 ng.L-1. The concentration range of total OCPs in Laolongdong was
17.7-40.8 ng.L-1 with a mean value of 32.7 ng.L-1. The OCPs component showed an
increasing trend from the entrance to the exit of those two underground rivers.
By analyzing the source of OCPs pollution, DDTs in the two underground river
basin came from the historical industrial DDTs input; chlordane mainly came from
atmospheric deposition. HCHs was the main source of Lin Dan's input, Nanshan
underground river was historical pollution, whereas there was a new HCHs input
from Ganjiachao in Qingmuguan upstream. Compared with the water bodies at home
and abroad, the concentrations of HCHs and DDTs in Nanshan underground river
water were at low level, whereas those in Qingmuguan were at medium to high
level. Comparing with the hygienic standard of foreign water, it could be
observed that Nanshan underground river and Qingmuguan underground river were not
able to meet the standard of drinking water safety standard. For the sake of
protecting the ecological environment of the underground river, land application
of organic chlorine pesticide should be banned in Qingmuguan.
PMID- 29964770
TI - [Comparison on the Hydrogeochemical Characteristics of Typical Karst Groundwater
System in Southwest China, a Case of Qingmuguan and Laolongdong in Chongqing].
AB - To study the hydrogeochemical characteristics of southwestern typical karst
underground river influenced by different land-use types and human activities,
underground rivers of Qingmuguan and Laolongdong, which have similar geological
background in Chongqing, were contrastively analyzed from the scale of monthly
and rainfall event variation. By the means of independent t-test and principal
component analysis(PCA), the results showed that ions of Ca2+, HCO3-, Mg2+, K+,
NO3-, Na+, SO42-, Cl- and conductivity were distinctly different at the outlet of
the two observed underground rivers, Jiangjia spring and Laolongdong. Compared
with Laolongdong, Jiangjia spring showed larger monthly variation range and mean
concentrations of K+, NO3-, but ions of Na+, SO42-, Cl- showed an opposite trend.
Water-rock interaction played an important role in the hydrogeochemical
characteristics and variations of two observed karst underground rivers.
Qingmuguan underground river was mainly affected by agricultural activities,
while Laolongdong underground river was dominantly influenced by urban and
industrial activities. Owing to the difference in manner and intensity of human
activities, the two observed karst underground river systems responded
differently during a single rainfall event. The variation of water chemical
indicators that highly corresponded to discharge at Jiangjia spring were
relatively disordered at Laolongdong. It was shown that the hydrogeochemical
characteristic of Qingmuguan was primarily influenced by soil erosion and
agricultural activities, followed by water-rock interaction, while the
hydrochemical characteristic of Laolongdong was dominantly influenced by water
rock interaction, followed by urban activities, industrial activities and soil
erosion.
PMID- 29964771
TI - [Fractions and Release Risk of Phosphorus in Surface Sediments of Three Headwater
Streams with Different Styles of Water Supply].
AB - From May to September 2015, seasonal sediment samples were collected from three
headwater streams and ditches which were discharged from sewage plant tail water,
food processing wastewater and agricultural drainage-groundwater seepage,
respectively, in Hefei, Chaohu Lake basin. The stream-bed sediments were analyzed
for phosphorus fractions. The risk assessment on phosphorus release from
sediments was conducted using the phosphorus sorption index (PSI), degree of
phosphorus saturation (DPS) and the phosphorus release risk index (ERI).
Moreover, nonparametric tests method was used to explore the difference among the
three studied streams and ditches. Study results showed that:1 Guanzhenhe
Distributary and Taochong Stream were seriously damaged by phosphorus pollution
both in waters and stream-bed sediment, and the phosphorus pollution levels could
be arranged in the order of Guanzhenhe Distributary >Taochong Stream >Modian
Stream. The mean content of total phosphorus (TP) in sediments in Guanzhenhe
Distributary was 1376.95 mg.kg-1, which was 2.94 and 1.91 times as high as those
of Modian Stream and Taochong Stream, respectively. 2 Significant differences and
different sort orders in contents of phosphorus fractions were found for each of
the three streams. 3 Obvious seasonal variations existed in PSI for the three
streams, and all the sampling points in the same stream had similar changing law,
namely, the maximum content emerged in autumn, followed by winter, and the
minimum occurred in spring or summer. 4 The same conclusions were drawn in
phosphorus release risk according to the PSI, DPS and ERI, and the risk ranked as
follows:Guanzhenhe Distributary >Taochong Stream >Modian Stream. 5 According to
the difference analysis, significant differences existed in almost all of the
indexes among the three streams.
PMID- 29964772
TI - [Vertical Variation of Phosphorus Forms in Lake Dianchi and Contribution to
Release].
AB - Columnar sediment samples were collected from the Waihai of Lake Dianchi in
northern, central and southern sediment, combined with the data of phosphorus in
the overlying water and sediment organic matter, the effects of organic matter
and particle size on sediment release were studied, and the influence of
different forms of phosphorus release from sediments and their contributions were
discussed. The results showed:Sediment pore water rho(DTP) and rho(SRP) was
negatively correlated with contents of OM, clay (<4.00 MUm) and silt (4.00-63.00
MUm), but it showed a significant positive correlation with sand (>63.00 MUm)
content. Theincrease in organic matter content of the sediments significantly
reduced the gap water phosphorus mass concentration, and increasing clay and silt
contents reduced the gap water phosphorus mass concentration, inhibiting the
release of phosphorus in sediments. Potentially mobile phosphorus of the Lake
Dianchi sediment was significantly positively correlated with the clay and silt
contents, and was significantly negatively correlated with the sand content. It
was indicated that clay and silt may enhance the phosphorus movement ability of
the sediment, and the sand may enhance the retention of phosphorus in the
sediment. In a short time scale, phosphorus of sediment was released mainly in
northern Waihai, staying mainly in central and southern; in a longer time scale,
phosphorus of sediment was released mainly in northern and central Waihai,
staying mainly in southern. Control of phosphorus release from sediments in Lake
Dianchi should take into account the effects of different forms of phosphorus,
organic matter and particle size, and take corresponding measures to control the
release of phosphorus in sediments of northern Dianchi mainly.
PMID- 29964773
TI - [Analysis of Distribution Characteristics and Source of Dissolved Organic Matter
from Zhoucun Reservoir in Summer Based on Fluorescence Spectroscopy and PARAFAC].
AB - The fluorescent components were examined using excitation emission matrix
fluorescence spectroscopy-parallel factor analysis technique for samples
collected in August, 2015 from Zhouncun Reservoir. Principal component analysis
was used to study the main factors and their relative contributions to DOM. Three
fluorescent components were identified by PARAFAC, including fulvic-like
component(C1:260,350/420 nm), protein-like(C2:280/360 nm) and humic-like
(C3:270,390/530 nm) which showed the same source. The even spatial distribution
of each component, higher total fluorescence intensity in storage port, high
fluorescence index, high biological index, low humification index and the
freshness index which was close to one showed that the DOM had a strong
autochthonous contribution. The results of PCA showed that the autochthonous
contribution reached 70.86%, and those three components of Zhoucun Reservoir
could be connected with aph(440) by nonlinear multiple regression which means we
can use the three-dimensional fluorescence spectrum results of DOM to control the
pollution sources and indicate the eutrophication degree of Zhoucun Reservoir.
PMID- 29964774
TI - [Absorption and Reflection Characteristics of Black Water Blooms in the Eutrophic
Water].
AB - Studying on optical properties of black water blooms, is the precondition for
using remote sensing technology to monitor and evaluate the black water blooms
event. Black water blooms occurred in Taihu Lake in July 2015. A total of 36
water samples were observed in the three water regions of Taihu Lake, the region
1 with black water blooms characteristics, region 2 with cyanobacterial bloom
characteristics, and regional 3 with characteristics of clean lake water. The
reflectance spectra and absorption coefficient of these three regions were
analyzed, and the results show that:1 The absorption coefficients of the total
particles, the pigment particles and the non-pigment particlesin black water
blooms are 1 to 2 times higher than the other two areas. The absorption
coefficient of CDOM between 400-500 nm in region 1 is about 2 times higher than
the other two areas, which lead the black water area with a very lower
reflectance, and presents as black color. 2 The range of M value in black water
blooms is lower than Dianchi Lake and Chaohu Lake, which means the humic acid
content of CDOM with black water characteristics is higher. A significant
positive correlation is found between chlorophyll a (Chl-a) and the CDOM
absorption coefficient at 350 nm, indicating that algae degradation is likely to
be the primary source of CDOM in black waters. 3 The contribution of each
optically active component indicates that the water absorption of region 1
strongly controlled by CDOM below 380 nm, but by Chla absorption between 380 nm
and 700 nm.
PMID- 29964775
TI - [Assessment of Ecosystem Health of Baogang Tailings Groundwater Based on
Microbiome Index of Biotic Integrity (M-IBI)].
AB - Index of Biological Integrity (IBI) is a scientific tool used to evaluate health
of aquatic ecosystems. IBI associates anthropogenic influences with biological
activity in the water body, and is formulated using data developed from
biosurveys. Compared with other biotic assemblage indicators of water quality,
little attention has been paid to the application of microbial community in
ecosystem health assessment for groundwater bodies so far. An approach based on
microbiome index of biotic integrity was developed to assess groundwater
ecosystem health in this study. The method based on Illumina high-throughput DNA
sequencing was applied to achieve the information of microbial community. The key
environmental factors were selected based on CCA analysis and the optimized
values were calculated for defining the taxonomic genera sensitive and resistant
to these factors. The resulting candidate biotic factors were used to construct
microbiome index of biotic integrity (M-IBI) evaluating system. The results
showed among the studied sample sites from groundwater of Baogang rare earth
tailings, 33.3% of samples were at "Great" level, 16.7% at "Good" level, most of
samples (41.7%) at "moderate" level and 8.3% at "Bad" level. The ecosystem
healthy status of the sample sites near the tailings was affected by human
disturbances, while the samples far away the tailings were at healthy level. The
results of the groundwater ecosystem healthy assessment based on M-IBI system had
a good match with the groundwater quality standard based on chemical properties.
It indicated that M-IBI could be a potential index to evaluate the health of
groundwater ecosystem.
PMID- 29964776
TI - [Relationship Between Landscape Pattern and Spatial Variation of Heavy Metals in
Aquatic Sediments in Headwaters Area of Yuqiao Reservoir].
AB - Yuqiao Reservoir, an important adjusting reservoir in the project of diverting
water from the Luanhe River to Tianjin City, is an important water resource for
Tianjin City. Concentrations and spatial variation characteristics of Cd, As, Pb,
Cu, Cr, and Zn from 33 sub watershed sampling sites of Yuqiao reservoir and the
relationship to landscape pattern were discussed. The result showed that average
concentrations of Cd, As, Cu, Cr in suspended particulate matter were higher than
Chinese environmental quality standard Grade one for soils, and there were
ecological risks for them because they could arrive at Yuqiao reservoir. The
average concentrations of Cd, As, Pb, Cu, Cr, and Zn in surface sediments were
0.32 mg.kg-1, 30.39 mg.kg-1, 33.49 mg.kg-1, 58.20 mg.kg-1, 90.16 mg.kg-1 and
94.80 mg.kg-1 respectively. The average concentrations of Cd, As, Cu and the
concentrations of Pb, Cr, Zn in partial samples exceeded Chinese environmental
quality standard Grade one for soils. The average concentrations of Cd, Cr, Zn in
surface sediments of three tributaries increased in the order of Linhe River
>Shahe River >Lihe Rier, Cu decreased in the order of Linhe River < Shahe River <
Lihe River, and As, Pb increased in the order of Shahe River >Linhe River >Lihe
Ricer. Land use types in Yuqiao reservoir basin had some impact on the
distribution of heavy metal concentrations in river surface sediments. Woodland
and shrub grass land determined the natural distribution trend of heavy metals in
surface sediments. Gardenland and industrial & mining land usage had impact on
Cd, As, Pb, Cr distributions. Farmland and village & town land usage did not
produce negative influence on heavy metal distribution.
PMID- 29964777
TI - [Effect of Constructed Wetland Configuration on the Removal of Nitrogen
Pollutants and Antibiotics in Aquaculture Wastewater].
AB - Horizontal subsurface flow constructed wetland (HSSFCW) and integrated vertical
flow constructed wetland (IVFCW) consisted of down-flow and up-flow were built to
treat aquaculture wastewater under different conditions. The water treatment
performance, especially the nitrogen pollutants and antibiotics removal
efficiencies, were compared, and the effects of flow patterns and hydraulic
retention time (HRT) on the efficiencies were studied. The results showed that
IVFCW had a better removal efficiency on nitrogen pollutants, and the removal
rates of TN and NH4+-N were 58% and 80% (HRT=3 d), respectively. Microbial
community was further analyzed using BIOLOG microplate technique and 454
pyrosequencing. The internal structure of IVFCW was conducive to the flow and
dissolved oxygen condition, which induced higher microbial activity and
diversity. The richness in Nitrospira distribution was the main reason for the
removal efficiency of ammonia nitrogen. HRT had a great influence on the removal
of NO3--N and NO2--N, and maintaining 3-4 d could reach good efficiency for all
kinds of nitrogen pollutants. Solid phase extraction-high performance liquid
chromatography-tandem mass spectrometry analysis (SPE-HPLC-MS/MS) was used to
test the removal efficiency of antibiotics, and the results showed that there was
no remarkable difference between the two configurations. The removal efficiency
of Enrofloxacin was higher than that of Sulfamethoxazole and Florfenicol.
Extending HRT from 1 d to 3 d could significantly improve the removal rate of
Sulfamethoxazole, reaching above 50%.
PMID- 29964778
TI - [Effects of a Symbiotic Bacterium on the Accumulation and Transformation of
Arsenate by Chlorella salina].
AB - Algae-bacteria consortia may be potentially applied in wastewater treatment and
environment remediation. In this study, in order to investigate effects of a
symbiotic bacterium on the accumulation and transformation of arsenate[As(V)] by
Chlorella salina, we used batch cultures to determine the uptake, adsorption and
transformation of As by axenic and non-axenic C. salina exposed to 0-750 MUg.L-1
As(V) for 7 d. The symbiotic bacterium of C. salina was confirmed to be Halomonas
sp. after isolation, cultivation and 16S rRNA identification. The bacterial
presence markedly increased the adsorption of As in C. salina, but it markedly
reduced the absorption and the toxic effect of As(V). Arsenate was the major
arsenic species in the cells of axenic and non-axenic C. salina. The proportion
of arsenite[As(III)] was 8.99%-11.52% in the axenic microalga whereas a small
quantity of monomethylarsonous acid (MMA) and dimethylarsinous acid (DMA) (0.02%
0.04%) were detected in the non-axenic counterpart. As(III) dominated the As
speciation in the bacterial culture and the percentage of As(V) was 7.59%-26.80%,
indicating that this symbiotic bacterium had a strong As(V) reducing ability. The
As removal rate (19.81%-41.08%) by non-axenic C. salina was higher than the
bacterium alone (5.14%-14.62%) and axenic C. salina (14.98%-21.08%) after 7 d
As(V) exposure. The symbiotic Halomonas sp. promoted the accumulation of As by C.
salina, indicating that algae-bacteria consortia might enhance the bioremediation
of As contaminated water.
PMID- 29964779
TI - [Effects of Nitrate in Water on the Growth of Iris pseudacorus L. and Its
Adsorption Capacity of Nitrogen in a Simulated Experiment].
AB - In order to provide references for the application of emergent plants in the
remediation and restoration of aquatic ecosystems, a hydroponic experiment was
conducted for Iris pseudacorus L. with different nitrate mass concentrations (i.
e., 10.68, 23.88, 42.22, 63.33, 82.92, 97.13 mg.L-1). The effects of nitrate mass
concentration in water on the growth and nitrogen absorption capacity of I.
pseudacorus were evaluated by the aboveground biomass, belowground biomass, root
shoot ratio, chlorophyll content, nitrogen uptake, and nitrate removal efficiency
of the plants. The following results were obtained from the experiment. 1 The
effects of nitrate mass concentration on the aboveground (stems and leaves)
growth of the I. pseudacorus were greater than that on the belowground (roots)
growth. Compared with the values before the experiment, the root-shoot ratio of
the I. pseudacorus increased in the treatment with 10.68 mg.L-1 of nitrate mass
concentration; while the root-shoot ratio decreased in the treatments with 42.22
97.13 mg.L-1 of nitrate mass concentration. 2 The I. pseudacorus grew better with
nitrate mass concentration ranging from 23.88 mg.L-1 to 63.33 mg.L-1; and the
chlorophyll biosynthesis of the plants was inhibited in the treatments with
10.68, 82.92, and 97.13 mg.L-1 of nitrate mass concentration. 3 The total
nitrogen accumulation of the I. pseudacorus was in range of 10.56-75.43 mg in the
experiment, which increased with the increase of nitrate mass concentration; and
the accumulation of nitrogen in the belowground parts was 7.2, 2.3, 2.5, 2.1,
1.6, and 1.5 times of that in the aboveground parts, respectively. 4 The nitrogen
utilization efficiency of the aboveground parts was higher than that of the
belowground parts. 5 The removal rates of nitrate by I. pseudacorus were 94.9%
99.3%, which increased with increasing nitrate mass concentration. The nitrate
mass concentration in water decreased with time in exponential function. In
conclusion, I. pseudacorus has promising performance in the removal of nitrate in
water, but its growth, nitrogen adsorption, and nitrate removal rate were
significantly affected by the nitrate mass concentration. Moreover, the response
of growth and nitrogen adsorption in aboveground of I. pseudacorus to nitrate
mass concentration was more sensitive than that in belowground.
PMID- 29964780
TI - [Adsorption Behavior of p-hydroxy Biphenyl onto Sediment of the Yellow River in
Lanzhou].
AB - In order to study the adsorption behavior of organic pollutants in sediment of
the Yellow River in Lanzhou, p-hydroxy biphenyl (PHB) was selected as the typical
organic pollutants to understand the adsorption kinetics and thermodynamics of
PHB onto sediment of the Yellow River in Lanzhou based on the batch experiments.
Meanwhile, the effects of systemic temperature, such as the particle size, the
initial concentration of PHB, pH value, and the ionic strength, were also
investigated for the adsorption of PHB onto sediment of the Yellow River. The
results indicated that the adsorption kinetics of PHB onto sediment of the Yellow
River could be better described by Pseudo-second-order model, and the boundary
layer and intraparticle diffusion were both involved in the adsorption kinetic
process. The adsorption thermodynamics of PHB onto sediment of the Yellow River
were fitted well with the Langmuir model(R2>0.974), which was a single molecular
layer adsorption process. The average adsorption free energy E ranged from 0.913
to 1.00 kJ.mol-1 when the systemic temperatures increased from 25C to 45C,
suggesting a physical adsorption. Thermodynamic parameter analysis indicated that
Gibbs free energy (DeltaGtheta) and Entropy (DeltaHtheta) were less than zero,
but Enthalpy (DeltaStheta) was more than zero in the adsorption process, which
tended to prove the spontaneous nature of the adsorption process, the endothermic
nature of the adsorption process and the increased randomness at the sediment
surface. Furthermore, the smaller the particle size, the greater the adsorption
capacity of the PHB. The adsorption capacity was increased with the increase of
the initial concentration of PHB. When the pH value in a range of 4.23 to 7.00,
the adsorption capacity of PHB showed a slow decreasing trend, while the
decreasing was sharp when pH value was greater than 7.00, and the adsorption
capacity was almost zero when pH value was about 10.3. With the increase of ionic
strength, the adsorption amount of PHB was also increased, but when the ionic
strength increased to a certain value, due to the competitive adsorption, the
adsorption of PHB onto sediments would be inhibited, resulting in decreased
amount of adsorption.
PMID- 29964781
TI - [Enhanced Pollutants Removal in a Municipal Wastewater Treatment Plant with
Multistage A/O Process].
AB - Removal of conventional pollutants as well as genotoxicity was studied along a
multistage A/O process, which was based on the monitoring data in a Municipal
Wastewater Treatment Plant (MWWTP) of Yixing City. The results showed that the
multistage A/O process removed (67.3+/-7.0)% of COD, (93.7+/-1.5)% of NH4+-N,
(65.3+/-7.9)% of TN and (60.0+/-18.7)% of TP, respectively, which played a
dominant role in the removal performance of the whole wastewater treatment
process. The multistage A/O process showed significant ability to reduce alkanes,
halogenated hydrocarbons and alcohols in the municipal wastewater, while it
failed to remove the aromatic proteins which were the main fluorescent substances
of this wastewater. Furthermore, the process removed 82.8% genotoxicity from its
influent. Low organic load, single-phase influent and undesirable carbon source
feeding pattern, which caused the downstream A/O stages being not fully utilized,
were considered as the predominant reasons for the relatively low performance of
the multistage A/O process. Multi-phase feeding and adjusting carbon source
feeding pattern were thereby proposed. The results were considered to be helpful
for improving the operational performance of the MWWTP and useful for performance
evaluation of MWWTPs with similar process.
PMID- 29964782
TI - [Performance of Nanofiltration for Improving the Drinking Water Quality in a
Water Supply Plant with Micropolluted Water Resource].
AB - Four nanofiltration membranes connected in series were used for improving the
drinking water quality in a water supply plant in south China with micropolluted
water resource. The performance of the nanofiltration for improving the drinking
water quality was investigated. The results showed that nanofiltration was
efficient for removal of both traditional water pollution indicators and organic
toxicants. More than 95% of TOC and UV254 were removed from the effluent of the
traditional water purification process in the water supply plant. The NF effluent
had a TOC of no higher than 0.3 mg.L-1 and a UV254 of below 0.005 cm-1. The
removal rates of haloacetic formation potential,trihalomathanes formation
potential, polycyclic aromatic hydrocarbon(PAHs)and organochlorinated
pesticides(OCPs)were 62%, 85%, 50% and 95%, respectively. Genotoxicity of the NF
effluent was undetectable in the umu-SOS test. Moreover, no significant
difference was observed in the organic pollutants removal of haloacetic formation
potential,trihalomathanes formation potential and OCPs among the four NF
membranes but in the removal of PAHs with relatively smaller molecular weight.
Nanofiltration showed higher removal rate of high-molecular-weight organic
matters over low-molecular-weight organic matters. By comparison, only 17% of
PAHs, 62% of OCPs and 80% of genotoxicity were removed by advanced treatment of
ozone (O3) followed by treatment with biological activated carbon (BAC) in this
water plant, indicating that nanofiltration was better for removal of organic
pollutants.
PMID- 29964783
TI - [Reaction Kinetics and Impacting Mechanism of Cr(VI) Removal in Fe0-PRB Systems].
AB - Zero-Valent Iron Permeable Reactive Barrier (Fe0-PRB) is a competitive and
economical in-situ groundwater remediation technology in recent years, and high
removal efficiencies of Cr(VI)-polluted groundwater have been realized. The
present study focused on the impacting mechanism of Cr(VI) removal by Fe0-PRB.
Environmental condition response was revealed from kinetic view, and kinetic
expression describing the removal process was determined. In addition, the effect
of groundwater chemical conditions was studied. It was found that calcium had
little effect on Cr(VI) removal. Chloride might influence Cr(VI) removal through
impacting electron transfer, and sulfate/magnesium might influence Cr(VI) removal
through participating in reactions. Bicarbonate might influence Cr(VI) removal
through combined effects of impacting electron transfer and participating in
reactions. The results provide method and theory basis for process parameter
optimization in Fe0-PRB systems.
PMID- 29964784
TI - [Adsorption Cd2+ from Solution by EDTA-modified Silicate Nanoparticles].
AB - Silicate nanoparticles(nSiO2) are a kind of widely used engineering material. In
order to improve the Cd2+ adsorption ability, the EDTA-modified nSiO2
nanoparticles were prepared by grafting method and characterized by TEM, N2
adsorption-desorption, FTIR, and TGA. The effects of solution pH, contact time,
temperature and ionic strength were examined. The adsorption mechanism was
further investigated by XPS. The results showed that the EDTA-nSiO2 nanoparticles
possessed excellent stability, and were successfully prepared. Cd2+ adsorption
was mainly controlled by solution pH. The raw nSiO2 had limited Cd2+ adsorption
ability, while the EDTA-modified nSiO2 particles had significantly improved
adsorption performance. At high pH, the Cd2+ adsorption rate increased and kept
balance above pH 4.0. The Cd2+ adsorption was an endothermic spontaneous process
which could be finished within 1 h. Langmuir model could be used to describe the
adsorption isotherm. The temperature ranged from 293-313 K during the process,
while the maximum adsorption was observed at higher temperature. Higher ionic
strength could inhibit the Cd2+ adsorption. The Cd2+ adsorption decreased from
0.433 to 0.294 mmol.g-1, when NaCl concentration varied from 0 to 100 mmol.L-1.
The desorption of Cd2+ from the EDTA-nSiO2 nanoparticles was carried out with
distilled water, 0.1 mol.L-1 NaCl and 0.1 mol.L-1 HCl. The maximum Cd2+
desorption of 94.36% was obtained at 0.1 mol.L-1 HCl. Based on the results of
thermodynamics, pH, ionic strength, and XPS analysis, it could be concluded that
Cd2+ adsorption was a multiple process dominated by chemical chelating reaction,
physical adsorption and ion exchange. This study indicated that the EDTA-nSiO2 is
an effective engineering nanomaterial that could be used in Cd2+ adsorption.
PMID- 29964785
TI - [Analysis and Characterization of Multi-modified Anodes via Nitric Acid and
PPy/AQDS in Microbial Fuel Cells].
AB - The properties of anode material are crucial for high performances in microbial
fuel cells (MFCs). Hereby, a biocompatible, conductive, and high electron
transfer ability anode was fabricated by electrodepositing
polypyrrole/anthraquinone-2, 6-disulphonic disodium salt (PPy/AQDS) onto nitric
acid-soaked carbon felt. The results showed that the multi-modified anode
outperformed the pristine one in biomass, electrical conductivity, and exchange
current density with between 2.4 and 3.3 times better performance. The multi
modified anode (applied with 0.12 C.cm-2 total charge density) showed the highest
peak current density (2.86 mA), the largest amount of biomass loading (0.44 mg.cm
2), the most favoured electrical conductivity (0.33 S.cm-1), and exchange current
density (3.65*10-3 A.m-2), as a result, the maximum power density of the MFC
equipped with the anode delivered a 2.2-fold increase over that of the control
(1060.7 mW.m-2vs. 477.6 mW.m-2), and thus has great potential to be used as an
anode for high-power MFCs. Further investigation revealed that the increased
energy output might be attributed to the bridging of the carbon fibers by
electrically conductive PPy/AQDS composite films, which provided a uniform
connection throughout the nitric treated carbon felt as well as the synergetic
effects between the newly formed functional groups like pyrrolic N and PPy/AQDS.
It was proposed that integrating biocompatibility (BCB) with electrical
conductivity (EC) and electron transfer efficiency (ETE) through multi
modification could form high-performance anode. Future efforts to be made for
realizing more extraordinary high-performance MFCs anodes were also outlined.
This work may also provide a novel universal approach for the development of
other types of anode for high-performance MFCs through integrating the BCB with
EC and ETE simultaneously.
PMID- 29964786
TI - [Adsorption Characteristics of Phosphorus Wastewater on the Synthetic
Ferrihydrite].
AB - The synthetic ferrihydrite, FerrorMox (FM), was used as adsorbent for removing
phosphorus from wastewater. SEM, EDS, XRD, FTIR and Raman were used to
characterize FM, and the results indicated that FM was amorphous 2 L ferrihydrite
and was composed of Fe, O, Ca and Si, etc. Afterwards, FM was applied to adsorb
phosphorus from wastewater, and the adsorption performance, influence factors and
adsorption mechanism were investigated. The phosphorus removal rate reached
99.14% under the condition of adsorption time of 60 min, initial pH phosphate
solution of 2, relative dosing quantity of 7 g.L-1, reaction temperature of 25C,
initial concentration of 10 mg.L-1, and solution volume of 50 mL. Adsorption
isotherms were well fitted with the Langmuir isothermal adsorption model at
different temperature with the correlation coefficient reaching above 0.95. The
thermodynamic parameters showed that the phosphorus adsorption by FM was a
spontaneous endothermic reaction. The phosphate removal kinetics well followed
both pseudo-first-order model and pseudo-second-order model. About 99% of
phosphate adsorbed on FM could be desorbed in 0.1 mol.L-1 NaOH solution.
Therefore, FM was a promising absorbent material for the removal of phosphate
from waste water.
PMID- 29964788
TI - [Polyhydroxyalkanoate (PHA) Synthesis by Glycerol-based Mixed Culture and Its
Relation with Oxygen Uptake Rate (OUR)].
AB - Polyhydroxyalkanoate (PHA) is one of the most promising biopolymers with the
advantages of biodegradable biocompatible and renewable. A glycerol-fed PHA
producing mixed culture was enriched in a feast-famine regime. The substrate
versatility and PHA production capacity of the mixed culture were studied using
acetate,propionate,butyric, glucose and lactate as substrate, respectively. The
results showed a high PHA content with lactate and acetate as the sole substrate,
respectively. When acetate and propionate were used as mixed substrates to
produce PHA, the PHA contents increased with the proportion of acetate and the
PHA content was the highest as the ratio acetate/propionate was 3:1.The results
based on the modeling of simultaneously storage and growth and the linear fitting
under three different acetate/propionate ratios showed that there was a linear
relation between PHA synthesis and OUR. Thus, it is feasible to estimate PHA
content based on in-situ real-time monitoring data of OUR.
PMID- 29964787
TI - [Performance of Bio-zeolite Constructed Wetland in Dispersed Swine Wastewater
Treatment].
AB - The anaerobically digested effluent of the dispersed swine wastewater was treated
by a three-stage bio-zeolite constructed wetland, and the performance of the
wetland, the variation of pollutants concentration in effluent and ORP
distribution in the bio-zeolite layer were studied. The results showed that COD,
N and P in the digested effluent could be efficiently removed by the wetland, and
the wetland also had resistance to ammonia impact load. When the hydraulic
loading rate was 0.047 m3.(m2.d)-1, COD, NH4+-N and TN (the average mass
concentrations in inflow were 477.7, 155.3 and 176.4 mg.L-1) were mainly removed
in the district 1 of the wetland, and the average removal rates were 80.6%, 55.3%
and 58.1%, respectively. There was obvious enhancement of nitrification in the
bio-zeolite, and the major nitrification product was nitrate. The mass
concentrations of NO3--N in the district 1, district 2 and district 3 of the
wetland were 85.85, 91.06 and 82.41 mg.L-1, respectively. The nitrate produced in
bio-zeolite layer of the district 1 could be denitrified by microorganisms in the
slag brick layer using the residual organic substances in water as the substrate.
TP was mainly removed by adsorption in the slag brick layer, and the role of
microbe assimilation was relatively small. The reaeration of the bio-zeolite
layer in the three-stage wetland was good. Most of the ORP values remained over
400 mV in the bio-zeolite layer.
PMID- 29964789
TI - [Kinetics and Mechanistic Investigation of the Photocatalytic Degradation of
Clothianidin].
AB - Clothianidin was selected as a model compound for kinetics and mechanistic
investigation of the photocatalytic degradation of nicotine insecticides. We
assessed the feasibility of the degradation process, and systematically explored
the effects of catalyst amount, reaction temperature, substrate concentration,
initial solution pH value, and the presence of inorganic anions and cations on
the reaction. The results revealed a Langmuir-Hinshelwood interaction of pseudo
first-order kinetics, showing a rate constant of 0.0506 min-1. The photocatalytic
degradation rate was the highest when the amount of catalyst (TiO2) was 3 g.L-1.
It was observed that an increase of reaction temperature or lowering of substrate
concentration was beneficial to clothianidin degradation. Additionally, the
initial pH value of the solution had an obvious effect on the degradation
process. Strong acid and alkali were not conducive and the degradation rate
constant was the largest at pH=5. Furthermore, most of the inorganic anions and
cations significantly hindered the degradation of clothianidin. Finally, the
degradation intermediates were identified by GC/MS, and the reaction pathways at
the initial stage of the photocatalytic process were proposed:hydroxylation of
parent compound, cleavage of N-N bond in the nitroguanidine group, and cleavage
of the C-N bond connected to the nitroguanidine and thiazole rings.
PMID- 29964790
TI - [Impacts of Industrial Zone in Arid Area in Ningxia Province on the Accumulation
of Heavy Metals in Agricultural Soils].
AB - With the transferring of the industry from the east coastal regions of China to
the mid and west regions, those places once called "Clean Earth" in the arid
north-west region are facing the contamination risks by industrial emission. In
order to study the impacts of the industrial zone on the accumulation of heavy
metals Zn, Cr, Ni, Mn, Co, Cu, Cd, Pb in agricultural soils, we collected the
agricultural soil samples in a county in Ningxia province using GIS technology.
Samples were collected in a belt way along the yellow river and expanding from
the industrial zone as the center according to the main local wind direction. It
was suggested that the accumulation of heavy metals in studied agricultural soils
was slight. High accumulation of Zn and Cd only occurred in several sites.
However, the accumulation of heavy metals in industrial zone was more apparent.
Except for Ni, the rest 7 elements had obvious accumulation. One third of the
sites had Cd concentration at contamination level. The spatial analysis revealed
that the distributions of Cd, Zn, Cu, Mn, and Pb were closely related to the
location of industrial zone. Industrial zone had not caused the contamination of
heavy metals in agricultural soils yet. Due to the high pH value (average pH
value of 8.54), no soil contamination issue was found at present. However, the
impacts of industrial zone on the accumulation of heavy metals in agricultural
soils were apparent. The input pathway of heavy metals into agricultural soils
was mainly dust deposition. The industrial zone also increased the heavy metal
concentrations in irrigation water to some extent.
PMID- 29964791
TI - [Pollution Characteristics and Health Risk Assessment of Polycyclic Aromatic
Hydrocarbons in the Surface Soils of a Large Steel enterprise in the North of
China].
AB - 16 priority control polycyclic aromatic hydrocarbons (PAHs) were analyzed by GC
MS in 22 surface soil (0-20 cm) samples collected from a large steel enterprise
in the north of China. The concentrations of Sigma16PAHs ranged from 22.0 MUg.kg
1 to 20062.0 MUg.kg-1. 4 to 5 aromatic rings were the dominant, typically
fluorene(Flu) and pyrene(Pyr). Compared with related domestic research, PAH
pollution in the steel enterprise reached medium level, with fifty percent of the
soil points were at moderate and severe pollution levels, mainly in the coking
and pellet plant area. The concentrations of 10 PAHs in 20 soil samples exceeded
the Dutch target reference values. Compared with soil screening value of Beijing
contaminated industrial sites, only part of the sample points exceeded the
standard, typically benzo[a]anthracene(BaA) and benzo[a]pyrene(BaP). The source
apportionment showed that soil PAHs mainly originated from combustion products of
coal and other fossil fuels with only a small portion contributed by oil
combustion and spill. The health risk assessment showed that the carcinogenic
risks of benzo[a]pyrene(BaP), benzo[a]anthracene(BaA),
dibenz(a,h)anthracene(DBA), benzo[b]fluoranthene(BbF), indeno[1,2,3
cd]pyrene(InP) exceeded the threshold of 1*10-6 under residential land condition,
the carcinogenic risks of benzo[a]pyrene(BaP), benzo[a]anthracene(BaA),
dibenz(a,h)anthracene(DBA) also exceeded the threshold of 1*10-6 under industrial
land condition. The carcinogenic risk value of benzo[a]pyrene(BaP) was the
biggest among the 16 PAHs. The soil PAHs in the steel enterprise already caused
harm to human health and the soil restoration project must be carried out.
PMID- 29964792
TI - [Vertical Distribution of Heavy Metals and Its Response to Organic Carbon in Red
Soil Profile].
AB - The vertical distribution patterns, the source and correlation of heavy metals
were characterized in the bulk soil and different soil aggregates of arable red
soil profile (0-100 cm) in Hunan province. Their response to organic carbons in
proflie was explored as well. Principal component analysis (PCA) suggested that
elements could be divided into two principal components, the metals of the first
group were Zn,Cu,Pb,As,Cd, and the second group metals were Cr, Ni. Priniciple
component elements had similar sources. In 0-30 cm, The first group metals
decreased with increasing depth, the second group metals increased with
increasing depth. The concentrations of typical heavy metals were in the order of
Zn >Cr >Cu >Pb >Ni >As >Cd. Cd in each soil layer was severely polluted, Zn was
at level of light pollution, while other metals were at clean levels. In terms of
different size of soil aggregate, it was found that colloids played an important
role in facilitating transport of heavy metals, such as As, Cu, Zn, Cd, Cr, Ni.
While Pb was still mainly enriched in clay component (<53 MUm). Infrared spectrum
analysis showed that the main functional groups of organic carbon were
polysaccharide (22.07%-47.13%), aromatic (13.88%-34.37%) and alcohol (21.04%
59.49%). Correlation analysis showed that stable organic carbon such as
polysaccharide and aromatic organic carbon could stablize the metals of first
group in profiles, which would delay the migration of heavy metals to deeper
soil. However, the active alcohol carbon would enhance the migration.
PMID- 29964793
TI - [Provoking Effects of Exogenous Zn on Cadmium Accumulation in Rice].
AB - Pot experiments were carried out to study the influences of different
concentrations of exogenous Zn on accumulation of Cd in various rice organs of
low Cd accumulation cultivar Xiang-Wanxian 12 (XWX12) and high Cd accumulation
cultivar Wei-You 46 (WY 46) exposed to soil with medium and serious Cd pollution.
The results showed that:In the soil with medium Cd pollution, Cd contents in
various rice organs of two rice varieties were increased by exogenous Zn, and the
Cd contents in brown rice of XWX12 and WY46 were increased by 125.0% -275.0% and
6.6% -91.2%, respectively, but still lower than 0.2 mg.kg-1. In the soil with
serious Cd pollution, Cd accumulation in various rice organs were reduced by
exogenous Zn. Cd contents in brown rice of XWX12 and WY46 were reduced by 16.6%
63.5%, and 15.6%-74.4%, respectively, and Cd contents in brown rice of WY 46 were
gradually decreased with increasing exogenous Zn application, resulting in lower
than 0.2 mg.kg-1 of Cd in brown rice. The correlations of Cd contents in brown
rice and exchangeable contents of Cd and Zn in soil were different depending on
the Cd pollution levels and the rice varieties. In the soil with medium Cd
pollution, Cd content in brown rice of XWX12 was linearly positively related to
exchangeable Zn content in soil, and Cd content in brown rice of WY46 was
linearly positively related to exchangeable Cd or Zn contents in soil. In the
soil with serious pollution, however, the correlation of Cd contents in brown
rice of WY46 and the contents of exchangeable Cd or Zn in soil was linear
negative correlation. Therefore, for improvement of the rice quality, under the
condition that total Zn content in soil was lower than the pollution level,
applying a certain amount of Zn to reduce Cd contents in brown rice was feasible
in the soil with serious pollution.
PMID- 29964794
TI - [Effect of Modified Biochars on Soil Cadmium Stabilization in Paddy Soil Suffered
from Original or Exogenous Contamination].
AB - To investigate the passivation of different modified biochars on the speciation
and availability of cadmium contaminated soil, the modified biochars were treated
by different approaches (acid/base treatment, impregnation with manganese oxides,
magnetic modification) and biochars(BC) were used as soil passivating agents for
soil culture experiments. The result indicated that the content of available
cadmium decreased significantly by BC and modified biochars in originally
contaminated soil. Compared with CK, the percentage of available cadmium in
originally contaminated soil was reduced by more than 50% using impregnable
biochars by KMnO4(BC-KMnO4) and basic biochars by NaOH(BC-NaOH). And the content
of available cadmium decreased significantly by three modified biochars which
were BC-KMnO4, BC-NaOH and FeCl3 magnetization biochars(BC-FeCl3) in exogenously
contaminated soil. Particularly, the best performance was observed with BC-KMnO4
that reduced 30% available cadmium in exogenously contaminated soil. However, the
passivation of BC was not significant, and the content of available cadmium
slightly increased (3.8%-24.5%) by BC-HNO3 in exogenously contaminated soil.
Furthermore, the content of exchangeable cadmium was increased by 20.2% with 2.5%
BC-HNO3 in exogenously contaminated soil, while significantly decreased by other
modified biochars and BC, and the 10% BC-KMnO4 reduced 65.1% exchangeable cadmium
in originally contaminated soil. Meanwhile, soil pH was increased significantly
by BC, BC-KMnO4 and BC-NaOH, while was reduced by BC-HNO3. The contents of
organic carbon and exchangeable base cations in soil were improved by all the
treatments. The results of regression analysis showed that the content of
available cadmium in originally contaminated soil was significantly negatively
correlated with soil pH, soil exchangeable Na+, while the content of available
cadmium in exogenously contaminated soil was significantly negatively correlated
with soil pH, soil organic carbon, soil exchangeable Mg2+, Na+, K+. Accordingly,
the lower available cadmium in contaminated soil may correlate with the
increasing content of organic carbon, exchangeable base cations and pH. In
summary, the materials of BC-KMnO4 could be used as a superior passivating agent
for in situ remediation of cadmium pollution, while the materials of BC-HNO3
could slightly activate cadmium in the soil, leading to some risk in in situ
remediation.
PMID- 29964795
TI - [Performance of Bioleaching Combined with Fenton-like Reaction in Heavy Metals
Removal from Contaminated Soil].
AB - Considering that heavy metal pollution problem is widespread in the soil of South
China, bioleaching process and bioleaching combined with Fenton-like reaction
were used to study the removal performance of Cu, Zn, Cd and Pb in the
contaminated soil around the lead-zinc mine in ShaoGuan City, Guangdong Province,
China. Sequential chemical extraction was applied to analyze the effects of
different treatments on the fracion distributions of Cu, Zn, Cd and Pb. The
results showed that 66.5% of copper,55.1% of zinc, 72.8% of cadmium and 35.6% of
lead could be removed after 12-day bioleaching process, among which, the
inorganic bound-fracion had the best dissolution efficiency. The rest of the
heavy metals in solid phase mainly existed in the form of stabilized residual
fraction. With an optimal H2O2 concentration of 5 g.L-1, the removal efficiencies
of Cu, Zn, Cd and Pb were 55.6%, 50.6%, 60.7% and 30.5% respectively after 2-day
bioleaching combined with Fenton-like reaction, which indicated that this
treatment was less effective than 12-day bioleaching, but significantly more
effective than the H2SO4 leaching, 2-day bioleaching, and Fenton reaction. The
bioleaching combined with Fenton-like reaction could realize the effective
dissolution of stable-state heavy metals such as residual fraction, organic bound
fraction and inorganic bound fraction in the soil, the contents of Cu, Zn, Cd and
Pb were below the limit value of standand of 50, 200, 0.3 and 250 mg.kg-1 after
the treatment, respectively. It possesses the advantage of high removal
efficiency in bioleaching and rapid reaction rate in Fenton reaction, thus, it is
a promising remediation treatment for heavy metal contaminated soil.
PMID- 29964796
TI - [Effect of Long-term Oil Contamination on the Microbial Molecular Ecological
Networks in Saline-alkali soils].
AB - Long-term oil contamination alters the structures of soil microbial communities,
as well as decreases the community diversity, posing a great threat to the
ecosystem. To determine the possible influence of long-term oil contamination on
microbial interactions in saline-alkali soils, microbial functional molecular
ecological networks were studied in both contaminated and uncontaminated soils
from Shengli oil field by constructing random networks based on null model. The
results demonstrated that the overall networks were significantly different
between contaminated and uncontaminated soils (P<0.001). Network size, links,
average connectivity, modules and modularity were all decreased in soil with oil
contamination, indicating that oil contamination altered the topological
structure of microbial functional molecular ecological network. Module hub and
connectors were different in contaminated and uncontaminated soils. The
topological roles of the genes (module hub and connectors) were altered by oil
contamination. Sub-networks of genes involved in alkane and polycyclic aromatic
hydrocarbon degradation were also constructed. Negative co-occurrence patterns
prevailed among functional genes, thereby indicating probable competition
relationships among functional groups.
PMID- 29964797
TI - [Effect of Nitrogen Deposition on Soil Microbial Community Structure Determined
with the PLFA Method Under the Masson Pine Forest from Mt. Jinyun, Chongqing].
AB - Nitrogen deposition increases the productivity of forest-land, yet may cause
environmental damage, while soil microorganisms are sensitive to the ecological
environment. The objective of this study was to investigate the effects of
nitrogen deposition on soil microbial communities and the relationship among soil
microbial communities, soil temperature, soil moisture and the concentration of
nitrogen deposition in the Masson pine forest. The results might provide a
reference for further study on the effects of nitrogen deposition on forest
ecosystem of Masson pine. From May 2014 to June 2015, three nitrogen application
treatments and the control treatment were set up:low nitrogen [N20,20 g.(m2.a)
1], moderate nitrogen [N40, 40 g.(m2.a)-1], high nitrogen [N60, 60 g.(m2.a)-1]
and control treatment [N0, 0 g.(m2.a)-1] in the Masson pine forest. Soil
microbial community structure, soil temperature and soil moisture were measured
by phosphorus lipid fatty acids (PLFAs) and automated soil CO2 exchange station.
The results showed that:1 Seasonal variation had a remarkable effect on soil
bacteria, fungi, actinomycetes and the total PLFA(P<0.05), all kinds of soil
microorganisms had the highest amounts in spring and the lowest in winter. In
different seasons, the response of different soil microorganisms to nitrogen
deposition was different. Generally, nitrogen deposition decreased soil
microorganisms in spring and autumn, while in summer and winter, nitrogen
deposition had a positive effect on soil microorganisms. 2 Nitrogen deposition
had a significant effect on soil microbial community structure(P<0.05). In spring
and summer, low nitrogen and moderate nitrogen decreased the soil microbial
richness index and diversity index, yet increased the evenness index. In the
autumn and winter, low nitrogen and moderate nitrogen promoted the soil microbial
richness index, diversity index and evenness index. In all four seasons, nitrogen
deposition reduced the soil microbial richness index, diversity index and
evenness index. 3 Correlation analysis showed that the concentration of nitrogen
deposition had a very significant negative correlation with soil bacteria
(P<0.01), and a significant negative correlation with total PLFA (P<0.05). Soil
temperature had a significant negative correlation with soil actinomycetes. Soil
moisture had a significant positive correlation with bacteria and total PLFA. In
conclusion, soil microorganisms of Masson pine forest were mainly influenced by
soil moisture and less affected by soil temperature in Jinyun Mountain. Nitrogen
deposition had a significant effect on microbial community structure and
diversity.
PMID- 29964798
TI - [Fungal Community Structure of Different Degeneration Deyeuxia angustifolia
Wetlands in Sanjiang Plain].
AB - To understand the wetland soil fungal community structure and diversity in
different degeneration Deyeuxia angustifolia wetlands, the topsoil (0-20) of
three different degeneration D. angustifolia wetlands were collected in the
Sanjiang Plain field experiment station of the Institute of Nature and Ecology,
Heilongjiang Academy of Sciences. The distribution and variation of soil fungal
diversity were assessed by high-throughput sequencing method. The results showed
that Shannon-Wiener index increased from marsh Deyeuxia angustifolia wetland
marsh meadow Deyeuxia angustifolia wetland meadow Deyeuxia angustifolia wetland.
Sequence blast showed that the fungal taxonomy belonged to Ascomycota,
Basidiomycota, Chytridiomycota, Fungi_unclassified, Zygomycota, which dominant
fungi were Fungi_unclassified (75.12%),Ascomycetes (56. 56%), Basidiomycetes
(72.65%) in the three degeneration wetlands, respectively. The fungal structure
compositions and diversities of marsh meadow Deyeuxia angustifolia wetland and
meadow Deyeuxia angustifolia wetland were similar according to Heatmap analysis.
The fungal community structure was influenced by soil nutrients (explained
88.62%) and plant composition (explained 9.85%) through the Variation partition
analysis (VPA). In conclusion, the fungal community structure was significantly
different, which was influenced by soil water content, in different degeneration
Deyeuxia angustifolia wetlands in Sanjiang plain. The results may supply
scientific basis for studying fungal diversity and spatial heterogeneity in
degeneration wetlands.
PMID- 29964800
TI - [Variation of Soil CO2 Flux and Environmental Factors Across Erosion-Deposition
Sites Under Simulation Experiment].
AB - The CO2 flux from soil is an important component of global carbon cycle, and a
small variation of soil CO2 flux can prominently influence atmospheric CO2
concentration and soil organic carbon stock. Soil erosion significantly
influences soil CO2 emission. However, the process of soil CO2 flux during soil
erosion and soil deposition remains uncertain. At the present study, a simulated
experiment on soil erosion and deposition was conducted at Changwu State Key Agro
Ecological Station, Shaanxi, China. From July to September in 2014 and 2015, soil
CO2 flux was periodically measured using an automated CO2 flux system LI-8100 (LI
COR, Lincoln, NE, USA) and soil temperature and moisture were collected by series
data collection system of soil temperature and soil moisture (EM50, DECAGON,
USA). The measurement frequency of soil CO2 flux was once a week during 09:00 and
11:00. Soil temperature and soil moisture of 10 cm topsoil were measured
continuously (at an interval of 30 minutes) during the experiment. At the same
time, runoff and sediment were collected as well in each rain event, and then SOC
content in sediment was measured. The results showed that soil CO2 flux between
erosion and deposition sites had a significant difference (P<0.05), and soil CO2
flux at deposition site [mean value 1.38 MUmol.(m2.s)-1] was 31% higher than that
of soil CO2 flux at deposition site [1.05 MUmol.(m2.s)-1], while temperature
sensitivity at deposition site (Q10:8.14) was 3 times as high as that at erosion
site (2.34). Soil moisture at deposition site was 19% higher than that at erosion
site (P<0.05). Soil temperature was slightly higher at erosion site. The average
SOC content (7.26 g.kg-1) increased by 6% in the sediment compared with the
initial SOC content (6.83 g.kg-1). Soil moisture and SOC redistribution across
erosion and deposition sites were influencing factors for soil CO2 flux under
erosional environment. In conclusion, soil CO2 flux showed a significant
variation at erosion site and deposition site. Changes in soil moisture and SOC
contributed much to the difference in soil CO2 flux across erosion and deposition
sites.
PMID- 29964799
TI - [Short-term Effects of Nitrogen and Sulfate Addition on CH4 and CO2 Emissions in
the Tidal Marsh of Minjiang River Estuary].
AB - In April 2015, using enclosed static opaque chamber-GC techniques, the short-term
effects of nitrogen and sulfate addition on the CH4 and CO2 emissions were
measured in the Cyperus malaccensis marsh in the high tidal flat of the Minjiang
River estuary, and the key factors controlling the variation of CH4 and CO2 were
examined. The influences of nitrogen and sulfate addition on the CH4 and CO2
emissions were different in different time scales. CH4 emission increased
significantly under the NH4Cl (NH) and NH4NO3+K2SO4 (NS) additions (P<0.01),
CO2emission increased significantly with NS addition (P<0.05), but CH4 and CO2
emissions demonstrated an obvious fluctuation pattern with KNO3 (NO) and K2SO4(S)
additions. Compared with the control (CK), average CH4 emissions increased by
286.36% and 122.73%, respectively, in the NH and NS addition treatments, average
CO2 emissions increased by 39.92% and 34.24%, respectively, with the NH and NS
additions treatments. The nitrogen and sulfate addition changed the temporal
variation of CH4 and CO2emissions from the C. malaccensis wetlands in growing
season. Significant correlations were found among CO2, CH4 emissions, and soil
temperature, electrical conductivity (EC), DOC (dissolved organic carbon) and
NH4+-N (P<0.05 or P<0.01) in the treatments with NH and NS additions; and soil
temperature, EC, DOC and NO3--N (P<0.05 or P<0.01) in the treatments with NO and
NS additions. Temperature, EC and nitrogen availability were the dominant factors
controlling the temporal variations of CH4 and CO2emissions in estuarine tidal
marsh ecosystem.
PMID- 29964801
TI - [Interannual Variations of Soil Respiration and Its Temperature Sensitivity in an
Orchard in Jinci Region of Taiyuan City].
AB - Jinci area of Taiyuan city is a former hometown of rice, and with the cutoff of
the Jinci spring the land use in the area changed fundamentally from original
paddy rice to corn or orchard use. So it is very important to investigate soil
respiration after land use change and to analyze the relationship between soil
respiration (Rs) and soil temperature (Ts) and soil water content (SWC), and to
estimate soil carbon dioxide efflux in the region. For this purpose, we measured
Rs for seven years (2006 to 2012) with an interval of 1 to 3 times per month from
March to December in a field originally for rice but now Chinese jujube, and
analyzed seasonal, annual variations of Rs and relationships between Rs and both
Ts and SWC. The results showed that the seasonal variations of Rs against day
number of the year could be significantly fitted with a three-parameter Gaussian
equation while there was no significant correlation between Ts and SWC.
Significant exponential relationship between Rs and Ts over the season was found,
but not with SWC. Interannual average estimation of soil efflux between March and
December from the soil was (5.32+/-3.31) MUmol.(m2.s)-1, and was equal to 1690.2
g.m-2 from the same period ranging from 1294 to 2006 g.m-2. No significant
difference in annual efflux was found between the years. The sensitivity of Rs to
Ts, Q10 value, ranged from 1.54-2.20, 1.68-2.48 and 1.82-2.46, respectively, for
the Ts measurement at 5, 10 and 15 cm depths. The Rs at 10C, R10, ranged from
2.37 to 2.81, 2.43 to 3.13 and 2.59 to 3.47MUmol.(m2.s)-1, respectively, for the
Ts measurement at 5, 10 and 15 cm depths. Both the Q10 and R10 increased with
increasing Ts measurement depth. In comparison with the fitted one-variable of
temperature model, the two-variable model combining both the Ts and SWC together
could be well used to predict Rs over the season. Our research results can bear
important implications for the study of CO2 efflux in the region and similar
regions.
PMID- 29964802
TI - [Influence of Biochar on Greenhouse Gases Emissions and Physico-chemical
Properties of Loess Soil].
AB - Biochar is known to be a good soil amendment to improve soil physical and
biochemical characteristics, to increase crop yield, and to mitigate greenhouse
gas emissions from soils. In this study, five addition levels of apple tree
branches-derived biochar (0, 20, 40, 60, 80 t.hm-2) were used in field plot test.
The effects of biochar on soil temperature, soil aggregates, NO3--N, NH4+-N,
microbial biomass carbon and greenhouse gas fluxes were investigated during the
whole pepper growth season. The results showed that biochar amendment increased
the temperature moderation capability of soil and increased the content of soil
macro-aggregates, especially the content of aggregates with sizes >5 mm, 5-2 mm
and 1-0.5 mm. As compared with the control, the contents of NO3--N, NH4+-N and
microbial biomass carbon increased by 4.9%-33.9%, 9.1%-41.1% and 11.8%-38.5% with
the increase of biochar content respectively. Biochar amendment increased CO2
emissions and CH4 uptake by 6.73%-23.35% and 3.62%-14.17%, respectively. N2O
emissions and global warming potential (GWP) decreased at biochar levels of 20
and 40 t.hm-2 and increased when the biochar levels were 60 and 80 t.hm-2 as
compared with the control. The results suggested that as a soil conditioner,
biochar improved soil quality, soil fertility and function of agriculture soil on
carbon sequestion and decreased emission cut. In addition, the choice of biochar
level is very important.
PMID- 29964804
TI - [Effects of Canopy Temperature on Carbon Dioxide Exchange of Winter Wheat in
Taiyuan Basin].
AB - We measured daily changes of carbon dioxide exchange in a winter wheat site in
Taiyuan basin using chamber method for two years and analyzed relationships
between environmental factors affecting carbon exchange of the wheat, including
air temperature (Ta), soil temperature (Ts), canopy radiation temperature (Tc)
and carbon exchange of the wheat on daily and seasonal scales. The results showed
that variations of both Tc and Ta on daily and seasonal scales were consistent
with a correlation coefficient of above 0.90. On daily scale, the correlation
coefficients of NEE, gross primary productivity (GPP) and ecosystem respiration
(Reco) against Ts on most of the measurement days were smaller than those against
Ta or Tc, but the correlation coefficients for NEE, GPP and Reco against Ta and
Tc showed no difference. On seasonal scale, the relationships between GPP, NEE,
Reco and all the temperatures (Ta, Tc and Ts) showed a significant parabola
shape. Optimal temperature of Tc for photosynthesis was slightly lower than that
of Ta, but the difference between the optimal Ta and Tc was only about 1C.
Relationship between Reco and Ta for the two-year measurement data was better
than that with Ts, but correlation coefficients of Reco with Tc and Ta had nearly
no difference ranging from 0.95 to 0.96. Our results could give some implications
for ecosystem carbon exchange estimation with remote sensing method based on
canopy temperature.
PMID- 29964803
TI - [Effects of Elevated Ozone and Nitrogen Deposition on Photosynthetic
Characteristics and biomass of Populus cathayana].
AB - The open top chambers were used to explore the influences of nitrogen deposition
on the response of photosynthetic characteristics of Populus cathayana to ozone.
The results showed that the net photosynthetic rate (Pn), apparent electron
transport rate (ETR), excitation energy capture efficiency of PSII reaction
center (F'v/F'm), coefficient of photochemical quenching (qP), the maximum of
carboxylation efficiency (Vcmax) and the maximum rate of electron transport
(Jmax) were significantly decreased with the increasing O3 concentration.
However, intercellular CO2 concentration (ci) was significantly increased and
stomatal conductance (Gs) remained unchanged. There was significant difference in
biomass at the end of growing season. However, in a certain extent, nitrogen
deposition improved photosynthetic capacity and biomass of P. cathayana. The
interaction of O3 and nitrogen deposition was not significant in terms of plant
photosynthetic characteristics. The current results provided scientific basis for
the protection of P. cathayana in response to the global O3 concentration and
nitrogen deposition increase.
PMID- 29964805
TI - [Composition and Evolution Characteristics of Dissolved Organic Matter During
Composting Process].
AB - According to the fraction method presented by Leenheer, dissolved organic matter
(DOM) extracted from chicken manure with different composting time was
fractionated into five groups [i. e., hydrophobic acid (HOA), hydrophobic base
(HOB), hydrophobic neutral (HON) fractions, acid-insoluble (AIM) and hydrophilic
matter (HIM)] using the XAD-8 resin based on its polarity and electric charge
characteristics. The composition and structures of these fractions were
investigated by elemental analysis, FTIR and 1H-NMR spectra. The results showed
that the HIM and HOA fractions accounted for 32%-44% and 35%-47% of DOM,
respectively, during the composting process, while the sum of the fractions HOB,
AIM and HON was responsible for less than 25% of DOM. The HIM content decreased
while the hydrophobic component increased after composting. The elemental
analysis indicated that, during the composting process, the N, C, S content of
all five fractions increased, the H/C ratio decreased, but the humification
degree increased; The result from 1H-NMR analysis showed that the HIM had low
alkyl chain, short branched chain, high branches and carbohydrate structure,
which was opposed to the HON fraction. The composition of AIM was similar to that
of humic acids, while the HOB was rich in nitrogen-containing compounds. The
result from the FTIR analysis showed that the HOA and HOB fractions were rich in
abundant carboxyl, ester group and hydroxyl functional group. Besides the above
functional groups, the AIM and HIM were rich in benzene groups. The HON fraction
was rich in aliphatic functional group except for the abovementioned functional
groups. The aliphatic functional group was degraded and the benzene functional
group after composting.
PMID- 29964806
TI - [Effects of Acidic and Basic Modification on Activated Carbon for Adsorption of
Toluene].
AB - Activated carbons (ACs) were modified by acidic solutions (H2SO4, HNO3, or H3PO4)
and basic solutions (NaOH or NH3.H2O), then H2SO4modified ACs were re-modified by
basic solutions, respectively, in order to investigate the key factors of physico
chemical properties that mainly affected the adsorption of ACs. BET surface area,
micropore volume, and surface functional groups were characterized and the
adsorption capacity of toluene on the modified ACs was measured. Results showed
that BET area,micropore area and micropore volume decreased and the acidic
functional groups increased by the acidic treatment, while the basic treatment
showed the opposite changing trend in the physico-chemical properties of ACs.
Such changes might be associated with the acidity/alkaline and
oxidizability/reducibility of experimental solutions. The acidic treatment led to
a reduce in toluene adsorption capacities by 9.6%-20.0%, while the capacity
increased by 29.2%-39.2% using the basic treatment, compared to those in original
ACs. Correlation analysis revealed that there was a positive relationship between
toluene adsorption capacities and BET area, as well as micropore area and
micropore volume, and a negative relationship between toluene adsorption
capacities and acidic functional groups. Multiple regression analysis showed that
micorpore volume and acidic functional groups were key factors influencing the
toluene adsorption capacity. Furthermore, the adsorption capacity of toluene on
re-modified ACs was influenced by the amount of acidic functional groups (-COOH,
C=O, and -OH), of which -COOH was the most important factor affecting the
adsorption capacity. It is generally suggested that the modification of ACs
should focus on an increase in micorpore volume and a decrease in surface
functional groups, especially the amount of -COOH, in order to gain the
improvement of toluene adsorption capacities.
PMID- 29964807
TI - [VOCs Emission from Motor Vehicles in China and Its Impact on the Atmospheric
Environment].
AB - Volatile organic compounds (VOCs) are important precursors of O3 and secondary
organic aerosols (SOAs). In order to fully understand the impacts of VOCs from
motor vehicles on urban air quality, the current state-of-the-art research
results on source apportionment are systematically introduced. The contribution
of VOCs from motor vehicles to secondary pollutants in China is further
discussed. It was found that motor vehicle exhaust is the largest source of urban
atmospheric VOCs, and the average contribution ratio is up to 36.8%, wherein
motorcycles and light gasoline vehicles are the main emission sources. The
results showed that VOCs from vehicles play an important role in O3 and SOA
formation in urban areas, whereas with the improvement of emission standards and
operating conditions, the motor vehicle emission factors and ozone formation
potentials (OFPs) are obviously reduced. Moreover, the composition profile of the
exhaust is mainly composed of aromatic hydrocarbons and alkenes, which contribute
more to secondary pollution. This work can aid in providing data and theoretical
support for the control of VOCs from motor vehicles in the future.
PMID- 29964808
TI - [Quantification of the Influence of Industrial Emissions on Volatile Organic
Compounds (VOCs) Using PMF Model: A Case Study of Jiangbei Industrial Zone in
Nanjing].
AB - Volatile organic compounds(VOCs)are important precursors of ozone and secondary
organic aerosol. The effect of industrial emissions on ambient VOC concentrations
in the Jiangbei Industrial Zone in Nanjing was evaluated using the ambient VOCs
measurements taken at Nanjing University of Information Science and Technology
(NUIST) during March 2017. The monitoring data showed that the sum of 92 measured
VOCs (TVOCs) ranged from 10.3*10-9 to 200.5*10-9. Some VOC species, such as
ethylene, propene, benzene, styrene, and dichloromethane had abnormally high
values. Positive matrix factorization model (PMF) was used to identify the main
sources of VOCs. The results showed that industrial emissions on average
accounted for 50.0% of TVOCs, while petrochemical industry, chemical industry,
and paints & solvents use accounted for 14.9%, 19.3% and 15.8%, respectively.
During a VOC pollution episode, the contribution of industrial emissions reached
74.9%. The direction of industrial sources was determined by combining the wind
speed and wind direction data.
PMID- 29964809
TI - [Source Analysis of Volatile Organic Compounds in the Nanjing Industrial Area and
Evaluation of Their Contribution to Ozone].
AB - Ambient volatile organic compounds (VOCs) were continuously measured during the
high ozone (O3) periods from May 1 to May 31 and June 1 to July 16, 2015 at an
industrial area in the north suburb of Nanjing. A positive matrix factorization
(PMF) model and an observation-based model (OBM) were combined for the first time
to investigate the contributions of VOC sources and species to local
photochemical O3 formation. The average VOC concentrations in 2014 and 2015 were
(36.47+/-33.44)*10-9 and (34.69+/-34.08)*10-9, respectively. The VOC sources
identified by the PMF model for 2014 and 2015 belonged to 7 source categories,
including vehicular emissions, liquefied petroleum gas usage, biogenic emissions,
furniture manufacturing industry, chemical industry, chemical coating industry,
and chemical materials industry emission sources. The OBM was modified to assess
the O3 precursors' relationships. Generally, photochemical O3 production was VOC
limited, with positive relative incremental reactivity (RIR) values for VOC
species and a negative RIR value for NO. It can be seen that alkenes (1.20-1.79)
and aromatics (1.42-1.48) presented higher RIR values and controlling O3 would be
the most effective when the VOC emissions from alkenes were reduced by 80%.
Vehicle emissions (1.01-1.11), LPG (0.74-0.82), biogenic emissions (0.34-0.42),
and furniture manufacturing industry (0.32-0.49) sources were the top four VOC
sources making significant contributions to photochemical O3 formation, which
suggests that controlling vehicle emissions, biogenic emissions, LPG, and
furniture manufacturing industry sources should be the most effective strategy to
reduce photochemical O3 formation.
PMID- 29964810
TI - [Ozone Formation Potential and Priority Species of VOCs in an Industrial Park].
AB - Ground-level ozone (O3) pollution is a serious problem in major cities in China.
The control of its precursors, volatile organic compounds (VOCs), is a key to
limiting ozone production. The ozone formation potential of VOCs in an industrial
park in Tianjin was studied by collecting gas samples at the factory boundaries
of six representative enterprises. The PTR-TOF-MS was used to analyze VOCs
quantitatively. The VOCs/NOx ratio was used to determine the control strategies.
The priority VOCs were selected based on the entropy method. Our results
indicated that, the ozone formation potential concentration of enterprise F was
the highest with the concentration of 0.4233 mg.m-3 using the propylene
equivalent concentration (PEC) scale; the highest concentration was obtained at
enterprise C with 1.5733 mg.m-3 using maximum incremental reactivity(MIR) scale.
The result of PEC scale is closer to the O3 concentration, which is applicable to
the study of ozone generation in this industrial park. Ozone production is
sensitive to both VOCs and NOx in this industrial park, joint control should be
considered. Alkanes contributed most to ozone formation, followed by alkenes &
alkynes, alcohols, and aromatics. The prior VOC species that need to be
controlled include n-heptane and its isomers, n-nonane, n-octane and its isomers,
undecane, pentane, n-decane, and methanol.
PMID- 29964811
TI - [Characteristics and Source Apportionment of VOCs of a Petrochemical Industrial
Park During Autumn in China].
AB - An online continuous monitoring system was used to determine the volatile organic
carbons (VOCs) in the ambient air of a typical petrochemical industrial park in
autumn (Sep., Oct., Nov.) of 2014. The composition, photochemical reactivity,
temporal variation, and source of VOCs were analyzed. The results indicated that
the mixing ratio of VOCs in autumnal ambient air of the study area was higher
than those of other cities and industrial areas. Alkanes were the most abundant
group in the VOC mixing ratio, and no significant temporal difference was
observed among the three months studied. However, the alkanes, alkenes, and
aromatics presented obvious diurnal variation, with single peak and trough
values, while the acetylene exhibited "W"-shaped variation, with two minimum and
one maximum values. Source apportionment using positive matrix factorization
(PMF) indicated that the sources of VOCs in the study area of natural gas
transportation and solvents, such as from leakage or volatile oil refinery
processing, followed by other traffic sources and asphalt have some contribution.
Alkenes and alkanes were the dominant groups of the source apportionment
composition, as expressed by the propylene-equivalent (Propy-Equiv) and maximum
incremental reactivity (MIR) methods, respectively.
PMID- 29964812
TI - [Characteristics of VOCs Pollution in the Winter Atmosphere of a Typical
Petrochemical Industry Park].
AB - Concentrations of volatile organic compounds (VOCs) in ambient air of a typical
petrochemical industry park were measured using an on-line monitor (TH-300B) from
December 2014 to February 2015. The composition, temporal variations, sources,
and photochemical reactivity of VOCs were analyzed. Alkanes were the most
abundant VOC species and contributed to 86.73% to total VOC concentrations in
winter. Concentrations of TVOCs, alkanes, alkenes, and aromatic hydrocarbons were
high at night and low during the day. The changes in alkane and alkene
concentrations were consistent with those in TVOC concentrations. Using principal
component analysis and multiple linear regression (PCA-MLR) in combination, five
sources of VOCs were identified; fuel evaporation, industrial emissions, a mix of
gasoline vehicle exhaust and plant emissions, diesel vehicle exhaust emissions,
and fuel combustion with contributions of 60.02%, 8.50%, 2.07%, 12.21%, and
17.20%, respectively. Propylene-equivalent concentration (Propy-Equiv) and
maximum incremental reactivity (MIR) method were used to calculate the
contributions of VOCs measured in the study area to ozone production. Alkanes
contributed most to ozone production followed by alkenes and aromatic
hydrocarbons. The contribution rate of cyclopentane, n-butane, and 1-pentene were
higher owing to their long photochemical age in the study area.
PMID- 29964813
TI - [Emission Inventory and Pollution Characteristics of Industrial VOCs in Hangzhou,
China].
AB - For the 2022 Asian Games, a series of major events were held in Hangzhou City in
2016 at the international summit, where research on VOC emission inventories,
especially on industrial VOCs, has attracted the attention of local residents and
management departments. By taking a bottom-up approach, 3518 enterprises in more
than 30 industries in Hangzhou were investigated and an industrial VOCs emission
inventory for Hangzhou was established. Based on the data on regional emissions,
emissions intensity, and spatial distribution, the industrial VOCs emissions in
Hangzhou were systematically analyzed. The VOC emissions from industrial sources
in Hangzhou amounted to 36839.5 tons in 2015. Printing and reproduction of
recorded media; chemical raw materials and chemical products manufacturing; and
the metal, textile, rubber, and plastics products industries were the most
important sources of industrial VOC emissions in Hangzhou. The largest industrial
VOC emissions were measured in Xiaoshan District, followed by Fuyang District and
Dajiangdong Industrial Agglomeration Area. The highest VOC emissions intensity
was detected in Fuyang District, Jiande City, and Lin'an City. Industrial VOC
emissions were mainly concentrated in more intensive industrial areas in
Xiaoshan, Fuyang, Yuhang, and Dajiangdong Districts.
PMID- 29964814
TI - [Industrial VOCs Emission in Qinhuangdao].
AB - This study established a VOC emissions inventory for Qinhuangdao City using the
data on the product yield, raw material use, the concentration of VOCs, the
discharge flow, and activities of 609 enterprises. The amount of annual VOC
emissions obtained from direct measurements and emission factor methods was
8420.07 t; 48.9% of which was from the economechnological development district,
which is the major industrial source of VOCs in the region. Benzene, lipids,
alkanes, and ketones were the main industrial VOC components. For important VOC
emitting industries, processing of petroleum, coking, processing of nuclear fuel
contributed 30.35% of total VOCs emissions in Qinhuangdao, and manufacture of
chemical raw materials, chemical products contributed 14.42%. Solvent use was the
most important emission link, which accounted for 37% of total industrial VOCs
emissions. About 109 of 609 investigated plants have VOC treatment facilities,
69% of which are based on adsorption technology.
PMID- 29964815
TI - [Pollution Characteristics and Emission Coefficient of Volatile Organic Compounds
from Auto/motorcycle Parts & Accessories Manufacturing in Zhejiang Province].
AB - The status of volatile organic compound (VOC) treatment in auto/motorcycle parts
& accessories manufacturing in Zhejiang province was analyzed based on data from
a survey investigating 70 concerned enterprises conducted in 2015. The pollution
characteristics were further explored and the emission coefficient of VOCs
released from this industry was preliminarily calculated by analyzing the survey
data of 56 of the typical enterprises that had been screened further. The results
showed that about two thirds of the enterprises had been equipped with collection
and treatment facilities, but most of those facilities were running abnormally.
Solvent-based materials were used commonly in this industry, and the main VOCs
pollutants were xylene, butyl acetate, cyclohexanone, acetic ether, and toluene.
The VOCs emission coefficient of auto/motorcycle parts & accessories
manufacturing in Zhejiang was 414 g.(thousand yuan)-1, whereas the emission
coefficient of the enterprises producing parts & accessories for only auto was
294 g.(thousand yuan)-1. As for the the enterprises producing parts & accessories
for only motorcycle and for both auto and motorcycle, the emission coefficient
reached 715 g.(thousand yuan)-1.
PMID- 29964816
TI - [Stench Sources and Impact Analysis in Automobile Making].
AB - Volatile organic compounds (VOCs) are an important source of industrial stench.
This study was aimed at sampling and analyzing the stench source and its impact
on the sensitive spot residential areas, concentrating on certain automobile
manufacturing enterprise. The odor concentration and VOCs species of each vent
stack, plant boundary, and sensitive spot in the enterprise were determined for
November 15 and 17, 2016 via qualitative and quantitative analysis using the
triangle odor bag method and gas pre-concentration system-gas chromatography-mass
spectra. The results show that the odor concentrations of all vent stacks in the
original equipment manufacturing plant and the engine plant were below the
criterion level, those of the plant boundaries in the engine plant were below the
limits, and those of the plant boundaries and sensitive spots in the original
equipment manufacturing plant exceeded the allowed standards. A total of 54 VOCs
species were identified, including aromatics, halogenated compounds, alkanes,
alkene, cycloalkanes, ketones, esters, ethers, alcohols, sulfur compounds, and
oxygen ring compounds. Halogenated compounds were the most abundant VOCs species,
followed by aromatics. As a result, aromatics and halogenated compounds are the
representative odorants in automobile making. 1,3-Butadiene and ethyl toluene
were selected to be the typical odorants of sensitive spots according to mass
concentration, detector odor threshold, and threshold dilution multiples of
characteristic VOCs species in sensitive spots. The results show that the
majority of characteristic VOCs species were from paint composition through the
qualitative analysis based on paint used in coating shops. 1,3-Butadiene, which
contributed the most to odor pollution, excluding the impact of other emission
sources on sensitive spots, originates from spraying and drying processes of
coating shops in the original equipment manufacturer. It is recommended that the
enterprise should adopt environmentally friendly paints with low VOCs components
or RTO purification equipment with higher processing efficiency to reduce the
impact of stench on the sensitive residential areas from automobile making.
PMID- 29964817
TI - [Pollution Characteristics and Health Risk Assessment of VOCs Fugitively Emitted
from Typical Brewers].
AB - Food processing plants are an important industrial source of volatile organic
compounds (VOCs). Research on the unorganized emissions of VOCs to the
surrounding environment from food processing plants is still quite scarce. The
purpose of this study was to investigate the concentration characteristics, odor
pollution, and health risk of the VOCs fugitively emitted from the brewing
industry. The concentration characteristics of VOCs fugitively emitted from a
typical vinegar factory and a typical distillery were detected via portable gas
chromatography-mass spectrometry. The thresholds of the diluted multiple and
sensory methods were also used for analyzing the VOCs. In addition, the
assessment of health risk was conducted according to the US EPA evaluation model.
The results show that the concentrations of the total VOCs emitted from the
vinegar factory and the distillery were 0.968 mg.m-3 and 0.293 mg.m-3,
respectively. Ethyl acetate and acetic acid were the main VOCs in the atmosphere
of the vinegar plant, accounting for 76.3% and 13.5% of the total VOCs,
respectively. The VOCs of the distillery were mainly characterized by ethanol and
ethyl acetate, which accounted for 56.3% and 30.4% of the total VOCs,
respectively. Oxygen-containing VOCs were the most important component of the
studied brewing industry source. The total odor indices of the VOCs emitted from
the vinegar factory and the distillery were both higher than 1, which indicates
that their unorganized emission of VOCs have odor pollution to the atmosphere.
The odor concentrations of the vinegar factory and the distillery were also
higher than the standard limit of malodorous pollutants. The results of the
health risk assessment show that the carcinogenic risk indices of VOCs were
2.45*10-6 and 5.25*10-6, respectively, which exceeded the suggested risk value by
the EPA but were lower than the OSHA and ICRP values.
PMID- 29964818
TI - [Pollution Characteristics and Health Risk Assessment of Atmospheric VOCs in
Chengdu].
AB - Volatile organic compounds (VOCs) were measured in atmospheric samples collected
from urban and roadside atmospheric environments in Chengdu in September 2012.
The composition, chemical reactivity, and concentration level and its variation
characteristics of VOCs were studied, and the health risk of aromatic compounds
was assessed. Results showed that the mean mass concentrations of total VOCs
(TVOCs) were (108.57+/-52.43) MUg.m-3 and (132.61+/-49.31) MUg.m-3 for the urban
and roadside atmospheric environments, respectively. The highest mass
concentrations were observed for alkanes, followed by aromatics, alkenes, and
alkynes. Aromatics and alkenes contributed more to ozone formation potential
(OFP) of the urban and roadside atmospheric environments, and m/p-xylene,
toluene, ethene, o-xylene, and propene were the key reactive species. The values
of hazard quotient and hazard index were less than 1 for benzene, toluene,
ethylbenzene, and o-xylene (BTEX), showing that they had no appreciable risk of
non-cancer health effects on the exposed population. However, the value of cancer
risk was above the safety threshold for benzene, showing that it was a potential
cancer risk to the exposed population.
PMID- 29964819
TI - [Indoor Formaldehyde and Benzene Series in Shanghai Residences and Their
Associations with Building Characteristics and Lifestyle Behaviors].
AB - From March 2013 to December 2014, we on-site inspected indoor concentrations of
formaldehyde and a benzene series in 454 children's bedrooms that were decorated
earlier than one year before our inspection. Large differences existed in the
formaldehyde and benzene-series concentrations among individual bedrooms.
Bedrooms that were inspected in winter had significantly higher concentration of
formaldehyde than bedrooms that were inspected in other seasons (P<0.001), but
the benzene-series concentration had no significant seasonal difference. Among
bedrooms that were inspected in spring, those using different materials as wall
coverings had significant differences in concentrations of the benzene series.
Among bedrooms that were inspected in summer, those using different materials as
floor coverings had significant differences in concentrations of the benzene
series (P<0.01). Among bedrooms that were inspected in autumn, those with>5
household bonsais had significantly higher concentrations of formaldehyde than
other bedrooms did. Among bedrooms that were inspected in winter, those with
frequent use of air humidifiers and those in which pets were kept had
significantly higher concentrations of the benzene series than other bedrooms did
(P<0.05). These results indicate that, after a long time since decoration, the
types of household wall and floor covering materials still have certain
relationships with indoor benzene-series levels and, compared to decoration
materials, household ventilation perhaps has greater effect on indoor
formaldehyde levels. The indoor benzene-series level perhaps has associations
with indoor humidity level and the keeping of pets in households. Household
bonsaies may have limited effect on indoor formaldehyde and benzene-series levels
in residences that were decorated a long time ago.
PMID- 29964820
TI - [Emission Inventory of Anthropogenically Sourced VOCs and Its Contribution to
Ozone Formation in Jiangsu Province].
AB - Based on statistical activity data, emission factors, and source profiles, an
emission inventory of anthropogenic-speciated VOCs in Jiangsu province in 2015
was calculated. The ozone formation potential (OFP) of VOCs was estimated by the
maximum incremental reactivity (MIR). The result showed that the total
anthropogenic emission amount of VOCs in Jiangsu Province was 1927.8 kt in 2015.
Fossil fuel combustion, industrial processes, solvent utilization, biomass
burning, vehicles, and storage and transport contributed 7.38%, 27.93%, 39.56%,
3.55%, 16.18%, and 5.39%, respectively. Suzhou, Nanjing, and Xuzhou were the
three cities with the highest amount, contributing more than 200 kt of VOCs. The
total amount of OFP from 56 ozone-precursor VOCs was 5429.5 kt. The contribution
to OFP from the equipment manufacturing, vehicles manufacturing and building
decoration was 30%-60% more than their contribution to the emissions. The coating
VOC reduction would be more efficient for alleviating O3 pollution. The 10 VOC
species with the largest OFP contribution were m/p-xylene, ethylene, propylene,
1,3-butadiene, toluene, o-xylene, 1-butene, ethylbenzene, 1,2,4-trimethylbenzene,
and p-ethyltoluene, which contributed 75.63% of the total OFP.
PMID- 29964821
TI - [Emission Inventory of Anthropogenic VOCs in Jiangmen City].
AB - Anthropogenic VOC emissions are classified into four sources:industrial, mobile,
life, and agricultural. An anthropogenic VOC emission inventory in Jiangmen for
2014 was developed using both "top-down" and "bottom-up" emission factor methods,
based on statistical survey data. The results showed that the total anthropogenic
VOC emissions in Jiangmen were 75.09 kt. VOC emissions from the industrial,
mobile, life, and agricultural sources were 41.37, 19.16, 11.07, and 3.50 kt,
respectively, which contributed 55.09%, 25.51%, 14.74%, and 4.65% of the total
anthropogenic VOC emissions. Motorcycle manufacturing, container manufacturing,
coating, printing ink, manufacturing of paint and similar products, printing and
packaging printing, plastics and rubber products, artificial leather
manufacturing, leather tanning, burning of fossil fuels, manufacturing of basic
chemical raw materials, electronics manufacturing, adhesives manufacturing, and
furniture manufacturing are key industries in Jiangmen, each of which emit more
than 1000 t of VOCs annually. The main emission sources in Pengjiang, Jianghai,
and Heshan are industrial, which account for more than 50% of emissions in each
of these districts, whereas the main emission sources in Enping and Taishan are
agricultural. Districts and county-level cities will be able to achieve better
emission reduction by using the local VOC inventory in the formulation of VOC
emission reduction policies.
PMID- 29964822
TI - [Emissions, Chemical Composition, and Spatial and Temporal Allocation of the
BVOCs in the Yangtze River Delta Region in 2014].
AB - Based on the land surface vegetation data interpreted via remote sensing and the
meteorological conditions predicted via the WRF model, the MEGAN model was
applied to calculate the regional BVOC emissions in the Yangtze River Delta (YRD)
in 2014. The chemical components and the temporal and spatial allocations were
further analyzed. Results show that the annual BVOC emissions in the YRD were
1886 kt, in which isoprene emissions were 704.2 kt (accounting for 37.3%),
monoterpenes 303 kt (16.1%), and other VOCs 878.8 kt (46.6%). Seasonal variation
of the BVOC emissions was very significant. The BVOC emissions had a strong
seasonal pattern, with maximum emissions in summer, accounting for 60.9% (1088
kt) of the total, whereas the minimum emissions occurred in winter, accounting
for 3.2% (57 kt). Spatially, the southern YRD produced more BVOC emissions than
the northern part did. In Zhejiang, Anhui, Jiangsu, and Shanghai, the BVOC
emissions were 842 kt (44.6%), 760 kt (40.3%), 272 kt (14.4%), and 12 kt (0.7%),
respectively. This is mainly related to the distribution of vegetation types.
PMID- 29964823
TI - [VOCs Emission Inventory of Service Stations in a Subcenter (Tongzhou District)
of the City of Beijing].
AB - As a subcenter of the city of Beijing, Tongzhou District is faced with enormous
pressure from the rapid growth of VOCs emissions from service stations. In this
study, a set of bottom-up VOCs inventory estimation methods for service stations
in Tongzhou District is established. Using local VOCs emission factors of service
stations in Beijing, combined with gasoline and diesel sales from every service
station, a high resolution VOCs emission inventory of service stations in
Tongzhou District from 2015 to 2022 was established. The results showed the
following. 1An online monitoring system (OMS) based on unloading, refueling, and
tank pressure vapor emission control measures can reduce the VOCs emission factor
from 190 mg.L-1 to 115 mg.L-1, and when the percent onboard refueling vapor
recovery system (ORVR) Penetration reaches to about 50%, the emission factors can
be reduced to 131 mg.L-1 and 96 mg.L-1, respectively. The VOCs emission factor
(13 mg.L-1) of diesel from the service station is 0.8% of the uncontrolled
emission factor (1552 mg.L-1) of gasoline. 2The amount of VOCs emissions from
service stations in Tongzhou District was 97.8 t.a-1 in 2015, and the emissions
of gasoline and diesel were 96.2 t.a-1 and 1.6 t.a-1, respectively, accounting
for 98.4% and 1.6%. The emissions were mainly concentrated in the area
surrounding the new Beijing Municipal Government site. 3After implementation of
the vapor recovery requirements of "Beijing's Clean Air Action Plan from 2013
2017," considering the increase in oil sales from 2017 to 2022, VOCs emissions of
gasoline and diesel from service stations will decrease by 9% and 6%,
respectively, compared to those of 2015 in Tongzhou District. Assuming that the
OMS will also be installed at 28 (2000-5000) t.a-1 service stations by the end of
2022, VOCs emissions of service stations will be reduce by 13% compared to those
of 2015. 4The measure of restricting the number of vehicles in operation by 50%
can reduce VOCs emissions of service stations by (22+/-12)% every day during 2014
Asia-Pacific Economic Cooperation conference (APEC). 5It is suggested to
strengthen vapor recovery supervision on service stations in the area surrounding
the new Beijing Municipal Government site, and in summer and refueling idle such
as in noon.
PMID- 29964824
TI - [Pollutant Emissions from Diesel Buses Fueled with Waste Cooking Oil Based
Biodiesel].
AB - Two diesel buses respectively certified to meet China III and China V emission
standards were used as prototype vehicles, fixed on a heavy-duty chassis
dynamometer and driven according to a typical city bus driving cycle to analyze
the pollutant emissions and volatile organic compounds (VOCs). The buses were
fueled with diesel and waste cooking oil based biodiesel with 10 vol% blend ratio
(B10). The emissions of total hydrocarbon(THC), CO, particulate matter (PM), and
the number of solid particles with a diameter of 23 nm to 2.5 MUm (referred to as
"solid particulate number of PM2.5") from the bus certified to meet China V
(referred to as "China V bus") were 39.3%, 19.9%, 77.4%, and 28.4% lower than
those from the other bus certified to meet China III (referred to as "China III
bus"), while NOx emissions were 31.7% higher. Moreover, alkanes, alkenes,
aromatic hydrocarbons, and oxygenated compounds in VOCs emitted from the China V
bus were lower than those emitted from the China III bus, suggesting lower
atmospheric reactivity and smaller potential of secondary organic aerosol
formation. Compared with the emission results of two diesel-fueled buses, the B10
fueled buses emitted smaller amounts of THC, CO, PM, and solid particulate number
of PM2.5, lower oxygenated compounds but higher alkenes; slightly higher NOx
emissions than China III but slightly lower NOx emissions than China V.
Consequently, the atmospheric reactivity of VOCs in exhaust gas from the bus
fueled with B10 was higher than that from the diesel-powered bus.
PMID- 29964825
TI - [Treatment of the Waste Gas Containing Methyl tert-Butyl Ether via a Biotrickling
Filter].
AB - The performance and microbial communities of methyl tert-butyl ether (MTBE)
treatment using a biotrickling filter (BTF) that was inoculated with activated
sewage sludge were investigated. The BTF successfully started up within 23 days
when the inlet concentration of MTBE was 100 mg.m-3 and empty bed retention time
was 60 s, with 70% removal efficiency (RE). Under steady-state conditions, an
elimination capacity (EC) and a mineralization ratio of 13.47 g.(m3.h)-1 and 68%
were achieved, respectively. The ECmax was 21.03 g.(m3.h)-1 according to the
Haldane model, and a KS of 0.16 g.m-3 and KI of 0.99 g.m-3 were obtained. High
throughput sequencing was used to identify the community structure of the mixed
microbial consortium in the BTF. The results indicated that Methylibium sp.
(11.33%) and Blastocatella sp. (9.95%) were the dominant bacteria.
PMID- 29964826
TI - [Composite CVOCs Removal in a Combined System of Nonthermal Plasma and a
Biotrickling Filter].
AB - A coupling system of nonthermal plasma and a biotrickling filter was used to
remove a gas mixture of chlorobenzene (CB) and dichloromethane (DCE). The effects
of inlet gas concentration and gas flow rate on the removal of the target
pollutants in the coupling system were investigated at the frequency of 10000 Hz
and specific input energy (SIE) of 6111 J.L-1. Furthermore, the advantages of the
plasma-bio-coupled system were revealed by analyzing the relationship between the
degradation products and SIE, biomass, or biodiversity in the biotrickling
filter. The results showed that when the SIE and gas flow rate were constant,
increasing the initial concentration would decrease the removal efficiency of the
mixed gas. The optimal appropriate gas flow rate was 0.71 L.min-1 when
considering the cost. The CO2 production amount, CO2 selectivity, and chloride
ion concentration increased with the increase of SIE when both the CB and DCE
concentrations were 500 mg.m-3 and the gas flow rate was 0.71 L.min-1. The
protein content of the biofilter column gradually increased as the reactor
operation progressed, and the biomass of the lower layer was higher than that of
the upper layer. The high-throughput sequencing analysis showed that the
biological community in the biotrickling filter keeped rich and diversified.
PMID- 29964827
TI - [Pollution Characteristics and Health Risk Assessment of Volatile Organic
Compounds (VOCs) and Semi-volatile Organic Compounds (SVOCs) in Qiantang River's
Hangzhou Section During a Water Odor Pollution Event].
AB - For surface water samples collected from the Hangzhou section of Qiantang River
(before, during, or after the occurrence of a water odor pollution event), 125
kinds of volatile organic compounds (VOCs) and semi-volatile organic compounds
(SVOCs)were quantitatively determined via purge&trap-gas chromatography-mass
spectrometry and liquid-liquid extraction-gas chromatography-triple quadrupole
mass spectrometry. Then, the pollution characteristics of the VOCs and SVOCs were
analyzed, and the health risk of these compounds was assessed. The results showed
that 17 VOCs and SVOCs in the surface water samples of 4 monitoring sections were
detected, in a concentration range of 0.01-1.21 MUg.L-1, which is a low pollution
level. The concentration of dichloromethane was the highest of 17 VOCs and SVOCs,
accounting for 36.3%, and it was thus clear that dichloromethane was the main
contributing factor. During the water odor pollution event, the concentrations of
VOCs and SVOCs were significantly higher than they were in the three months
before or after the occurrence of the event, by 2.1-4.6 times, reflecting the
strong external source input. In addition, human health risk assessment of
ingestion through drinking water and absorption through skin contact was
performed using US EPA recommended methods. It indicated that the total non
carcinogenic and total carcinogenic risks (?HI and ?R) caused by VOCs and SVOCs
are 2.4*10-3-3.6*10-2 and 1.9*10-7-1.0*10-6, respectively, both of which belong
to the acceptable risk level. Therefore, although ?HI and ?R during the
occurrence of the odor event were significantly higher than those in the three
months before or after the event, the VOCs and SVOCs detected will not cause
obvious non-carcinogenic nor carcinogenic health effects on humans.
PMID- 29964828
TI - [Occurrence and Spatial Distribution of Volatile Organic Compounds in Urban
Drinking Water Distribution Systems].
AB - Volatile organic compounds (VOCs) in the urban drinking water distribution
systems for two coastal cities (S City and L City) in China were analyzed. Health
risk assessments of VOCs detected in tap water were performed, and the
distribution characteristics of VOCs in the tap water pipe network were also
investigated. Among 47 target VOCs, 16 compounds were detected, of which 11 were
detected in both S City and L City. Halogenated hydrocarbons were the most
commonly detected VOCs, with trihalomethanes (including bromodichloromethane,
dibromochloromethane, and bromoform) having the highest detection frequencies
(92%-100%). With the exception of bromodichloromethane and dibromochloromethane,
the maximum concentrations of detected VOCs in both cities complied with the
relevant limits regulated by the standards for drinking water quality (GB 5749
2006). For bromodichloromethane and dibromochloromethane, not only did their
concentrations exceed the standard limits of GB 5749-2006 (60 MUg.L-1 for
bromodichloromethane and 100 MUg.L-1 for dibromochloromethane), but their
lifetime cancer risks (LCR) were estimated at unacceptable levels (>10-4).
Therefore, these two compounds should be given sufficient attention or be
classified as priority control pollutants in municipal water supply networks. In
addition, the spatial distribution of eight VOCs with high detection frequencies
(>90%) in the tap water pipe network of S City was investigated. The
concentrations of VOCs (excluding toluene) in this urban drinking water
distribution system gradually decreased with increasing distance from the
drinking water treatment plant.
PMID- 29964829
TI - [Health Risk Assessment of Volatile Organic Compounds for Different Commuting
Modes].
AB - In order to overcome the shortcomings of a single commuting mode, eight VOCs
including benzene, toluene, xylene, ethylbenzene, styrene, formaldehyde,
acetaldehyde, and acrolein were studied in five commuting modes in Guangzhou.
Applying the Monte Carlo simulation method, we assessed the health risk of these
VOCs in five commuting modes, cars, air-conditioned buses, non-air-conditioned
buses, subways, and bicycles, and analyzed the sensitivity of each exposure
parameter. We used Crystal Ball 11.1 with 10000 iterations of independent runs
and 95% confidence interval. The results show that the commuters of air
conditioned buses and cars are subjected to a higher cancer risk, following the t
distribution and lognormal distribution with 1.65*10-5+/-5.74*10-9 and 5.01*10
6+/-3.56*10-11, with the probability of exceeding 10-6 of 97% and 74.85%,
respectively. The cancer risks of bicycles, non-air-conditioned buses, and
subways are smaller, but their averages are higher than 10-6. The commuters of
cars and air-conditioned buses were subjected to a larger non-cancer risk,
following the lognormal distribution of 2.51+/-2.74 and 1.20+/-1.36; the
contributions of acrolein are above 80%. The non-cancer risk of bicycles is the
smallest and will not be a threat to human health. Sensitivity analysis shows
that the sensitivities of ET, CA, ED, IR, and EF are larger, with the values of
55.5%, 32%, 10.5%, 1.1%, 0.2%, respectively, and BW has negative sensitivity.
PMID- 29964830
TI - [Source Analysis and Environmental Health Risk Assessment of VOCs in Furniture
Manufacturing].
AB - Regarding furniture manufacturing, scholars have only studied the sources of VOCs
in the spraying process, yet the main concern is the release of VOCs after the
completion of the manufacturing process and its impact on indoor air quality.
Therefore, in this study, the sources of VOCs for the entire process of furniture
manufacturing were explored and probabilistic risk models were improved. Then,
the carcinogenicity and non-carcinogenic health risks to workers at nine
workstations in a furniture factory were evaluated via a Monte Carlo simulation
method, and the sensitivity of each exposure parameter was analyzed. The results
are as follows. The various types of paints, diluents, and curing agents used in
the process of spraying primer paint and spraying surface paint release VOCs,
such as benzene, toluene, xylene, styrene, butanone, cyclohexanone, butyl
acetate, and ethyl acetate. The glue used in the leather pasting process, the
glue process, and the viscose process generates VOCs, such as dichloromethane and
ethyl acetate, and the paint remover used in the cleaning process emits
dichloromethane. The carcinogenic risk at each station was more than 10-6. For
benzene exposure, the probability of exceeding 10-6 was greater than 95% for all
stations, excluding SWB, SWP, and CWP. The carcinogenicrisk of workers exposed to
benzene was the highest at SWS, at 3.07*10-6+/-1.73*10-6, and the
carcinogenicrisk of workers exposed to dichloromethane was the greatest at SWL,
with a value of 5.14*10-6+/-2.70*10-6. The only non-carcinogenicrisk greater than
1 was to SWS workers. The parameters that had the greatest impact on the
carcinogenic risk assessment were exposure day (ED), concentration (C), exposure
time (ET), and exposure frequency (EF). In the non-carcinogenic risk assessment,
the most influential variables were ED, ET, and EF. In addition, concentration
also had a significant impact on the evaluation results.
PMID- 29964831
TI - [Spatio-temporal Distribution Characteristics of PM2.5 and Spatio-temporal
Variation Characteristics of the Relationship Between PM2.5 and PM10 in Beijing].
AB - Spatio-temporal distribution of PM2.5 and variations in the relationship between
PM2.5 and other pollutants are the main components of PM2.5spatio-temporal
statistical analysis. Existing methods directly analyze spatio-temporal
distribution based on monitoring data; thus, it is difficult to effectively
reveal the aggregation structure of PM2.5 concentrations. Geographically weighted
regression, commonly used to model the relationships between PM2.5 and other
pollutants, cannot accurately describe the spatio-temporal variability of
dependency. In this study, the clustering structure of PM2.5 concentrations in
Beijing was identified using the spatial clustering algorithm and the seasonal
distribution characteristics of PM2.5 were analyzed based on the clustering
results. The relationship between PM2.5 and PM10 was modeled by geographically
and temporally weighted regression and the spatio-temporal variability of
dependency was analyzed according to the regression results. The results showed
that PM2.5 pollution levels and spatial variability were lower in spring and
summer than those in autumn and winter and the concentration of PM2.5 in each
season was characterized by low spatial distribution in the north and high
spatial distribution in the south. Geographically and temporally weighted
regression showed better performance; the correlations between PM2.5 and PM10 in
spring and summer are weaker than those in autumn and winter and the correlation
between PM2.5 and PM10 in the northwest is stronger than that in the southeast in
each season.
PMID- 29964832
TI - [Quantification of Methane Ebullition Flux from Small Ponds Using the Inverted
Funnel Method].
AB - To quantify the ratio of CH4 ebullition to total flux in subtropical shallow
ponds, the CH4 flux at the water-air interface was measured using the inverted
funnel and water equilibrium methods in two small ponds in Quanjiao, Anhui
Province from July 28 to August 13, 2016. The average CH4 ebullition fluxes were
121.78 and 161.08 mg.(m2.d)-1 and the average diffusion fluxes were 3.38 and 3.79
mg.(m2.d)-1 over pond A and pond B, respectively. The ebullition flux accounted
for 97.5% and 96.4% of the total flux over pond A and pond B, respectively.
Methane ebullition ranged from 0.11 to 446.90 mg.(m2.d)-1 over pond A and from
0.05 to 607.51 mg.(m2.d)-1 over pond B. Gas ebullition rate during the day was
higher than that at night and was controlled by wind speed. Methane ebullition
flux was influenced by wind speed over the shallow pond at hourly scale and by
water depth and wind speed at daily scale, with positive correlation with wind
speed and negative correlation with water depth. Varying with latitude, methane
ebullition flux was higher for the water bodies in the mid-latitude region
compared to those in the high-latitude region. Direct observations of the methane
ebullition flux over small ponds provide data support and theoretical reference
to precisely estimate the contribution of inland water bodies to regional and
global carbon cycle.
PMID- 29964833
TI - [Contamination Levels and Exposure Risk via Drinking Water from Perfluoroalkyl
Acids in Seven Major Drainage Basins of China].
AB - To study the perfluoroalkyl acid (PFAAs) contamination in seven major drainage
basins of China and the exposure risk to resident populations via drinking water
sourced from these basins, a risk assessment model of the US EPA and a scenario
based risk assessment method were applied to analyze the PFAA pollution
characteristics and to evaluate the average daily dose and health risk to adults,
adolescents, and children. In the intermediate-exposure scenario, results showed
that the ?PFAAs median for the seven major drainage basins was 14 ng.L-1, with
perfluorooctanoic acid (PFOA), perfluorobutanoic acid (PFBA), and perfluorooctane
sulfonic acid (PFOS) the main contaminants, and that the contamination levels
were the highest in the Songliao River and Taihu Lake basins. In the high
exposure scenario, the discharge proportion of perfluoroalkyl carboxylic acids
with <= 6 carbon chains among the ?PFAAs was higher than that in the intermediate
exposure scenario. In addition, certain sections tended to be more polluted than
others in the Yellow River and Yangtze River basins. Risk assessment showed that
PFOA and PFOS exposure via drinking water posed no health risk to Chinese
residents, and that the average daily ingestion of drinking water of Chinese
adolescents was below the suggested amount.
PMID- 29964834
TI - [Spatio-temporal Distribution and Source Apportionment of Nitrogen in Rivers of
Tieling].
AB - This study analyzed the spatio-temporal distribution and sources of nitrogen (N)
in 22 rivers in Tieling City during 2013-07-2014-07. The results showed that the
concentrations of TN, NO3--N, and NH4+-N were 1.26-18.85, 0.53-11.8, and 0.3-15.7
mg.L-1, with an annual mean value of (5.8+/-1.9), (2.8+/-1.74), and (2.0+/-1.1)
mg.L-1, respectively. Overall, NO3--N was the main form of N with a percentage of
48%. The concentration of N in the wet season was significantly higher than that
in the normal and dry seasons. According to the standards for surface water
quality, water quality in eight rivers was worse than grade III. Tiaozi River and
Xiaoqing River were seriously polluted by ammonia N with a grade V water quality
through the sampling period, while Xiliao River, Xiaohezi River, and Liao River
met the water quality standards. During the sampling period, delta15 N and
delta18 O in nitrate in river waters were -3.00/00-23.90/00 and -11.70/00-570/00,
respectively. Based on the data on the isotopes of N and O, N in the rivers in
Tieling City mainly originated from human and animal excreta, industrial
effluents, and domestic sewage. Sources of riverine N varied with seasons. For
example, N in Tiaozi River and Nianpan River was mainly from fertilizer use and
soil nitrogen in the wet season while it was from the industrial effluents and
domestic sewage in the dry season.
PMID- 29964835
TI - [Characteristics of Chromophoric Dissolved Organic Matter (CDOM) in Rivers of
Western Sichuan Plateau Based on EEM-PARAFAC Analysis].
AB - Alpine meadows and wetlands of western Sichuan plateau are essential organic
carbon pools for Tibetan plateau; thus, a thorough understanding of the
characteristics of dissolved organic carbon (DOC) and its association with soil
carbon storage pool helps to reveal the flux and intensity of DOC export in the
area. Surface water samples were collected from three rivers (the upper reaches
of Min River, Zagunao River, and Fubian River) in the alpine-gorge region and Bai
River in the plateau planation surface distributed among the watersheds in
western Sichuan plateau, Southwest China. UV absorbance and EEM fluorescence
spectroscopy with parallel factor analysis (PARAFAC) was used to characterize
chromophoric dissolved organic matter (CDOM). PARAFAC produced a three-component
model:C1(260/480) and C2(310/420) represented terrestrial humic-like
fluorophores, and C3(280/370) belonged to tyrosine-like substances. The total
fluorescence intensity of CDOM in the alpine-gorge region showed fewer changes
along the rivers and was lower than that of the Bai River in the hilly plateau.
The Bai River had much higher concentrations of humic-like substances (C1,C2)
compared to the other three rivers, indicating its terrestrial sources with high
humification degree originated from meadows and watersheds along the river. The
calculated fluorescence indices (FI, BIX, HIX, beta:alpha) showed that CDOM in
the alpine-gorge region was a mixture with both autochthonous and allochthonous
origins with low humification degree, while CDOM in the plateau planation surface
had a higher degree of humification and lower extent of degradation. Statistical
analysis showed that the C1 and C2 components in four rivers were significantly
positively correlated, and C1, C2 and C3 components in Bai River were
significantly positively correlated. beta:alpha and BIX were significantly
positively correlated in four rivers, but there was no significant correlation
between DOC and CDOM[a(355)].
PMID- 29964836
TI - [Assessment of Heavy Metal Pollution and Human Health Risk of Surface Waters in
the City of Ningbo, China].
AB - In order to evaluate the present situation and the potential ecological risk of
heavy metal pollution in the surface waters of eastern Chinese coastal cities,
the city of Ningbo was used as an example. From surface waters in Ningbo, 255
water samples were collected. The concentrations of six heavy metals (Cd, Cr, Cu,
Ni, Pb, and Zn) were measured for the samples. The potential ecological risk of
these heavy metals was evaluated by calculating health risk and cancer risk
indices. The results indicate that, in the surface waters of Ningbo, the average
concentrations of the six heavy metals were in the increasing order of Zn > Pb >
Cr > Ni > Cd > Cu. Three of the heavy metal concentrations exceeded the national
environmental quality standards for surface water (GB 3838-2002, grade V), and
the order of exceeding the standard:Cd > Pb > Cr. Electroplating wastewater,
metal waste produced, traffic pollutant, dyes, and coatings waste were the main
pollutant sources. There were some potential health risks in over 70 percent of
the surface waters in Ningbo, and the surface waters of the Zhenhai and Haishu
districts had the highest potential health risk. There were three major potential
health risk heavy metals, and their order of increasing risk was Cd > Cr > Pb.
For adults and juveniles, the average carcinogenic risk indices were 17600 and
24800 times the critical values, respectively. Moreover, over 95 percent of the
risks were attributed to Cr. The potential carcinogenic risk index of commercial
areas with dense population was nearly 2 times that of the city average. The
results indicated that the state of heavy metal pollution in the surface waters
of Ningbo was very serious, thus the government should pay more attention to this
issue.
PMID- 29964837
TI - [Temporal-spatial Distribution and Pollution Assessment of Dissolved Heavy Metals
in Chaohu Lake].
AB - Surface water samples were collected in different seasons from Chaohu Lake to
determine the concentrations and potential environmental impacts of nine
dissolved heavy metals (As, Hg, Cd, Cu, Pb, Zn, Cr, Ni, and Co). The
concentrations of the selected heavy metals were determined by inductively
coupled plasma-optical emission spectrometry (ICP-OES, ICAP6000 series). The
single pollution index method and integrated pollution index method were used to
evaluate the potential environmental impacts. The results indicated that the
contents of dissolved As, Cd, Pb, and Cr in Chaohu Lake were lower than the
limitations of GradeIof the Environmental Quality Standards for Surface Water (GB
3838-2002), while Cu and Zn were within the limitations of GradeI-II and Hg was
within the limitations of GradeI-III. The contents of Ni and Co were far below
the limitations. The concentrations of the selected heavy metals (Cu, Pb, Zn, Cr,
Ni, and Co) varied among seasons and areas. Elevated concentrations of Cu, Zn,
and Ni were found in summer, while elevated contents of Pb, Cr, and Co were found
in autumn, autumn, and spring, respectively. Trace elements in the western part
of Chaohu Lake (especially in the northwestern part) were higher than those in
the middle and eastern parts for autumn, winter, and summer. Significant positive
correlations were found among Cu, Pb, Zn, Cr, and Ni in the surface water,
suggesting that these elements may derive from similar sources. The values of
both the single factor pollution index and integrated pollution index of the
selected elements in the surface water were far less than 1, suggesting that the
environmental impacts could be regarded as negligible. The integrated pollution
indices in the western part of the lake were higher than those of the middle and
eastern parts on a one-year timescale, and the integrated pollution indices in
each lake area followed a pattern of wet season (summer) > normal season (spring
and autumn) > dry season (winter).
PMID- 29964838
TI - [Spatial Distribution, Sources and Bioavailability of Heavy Metals in the Surface
Sediments of Longjiang River, Southern China].
AB - In order to evaluate the pollution status, possible sources, and bioavailability
of heavy metals (As, Cd, Pb, Sb, Zn, and Tl), 33 surface sediments were collected
from Longjiang River, Southern China. The total concentrations and potential
bioavailable concentrations of the heavy metals were analyzed using ICP-MS.
Enrichment factors (EFs), Pearson correlation analysis, and principal component
analysis (PCA) were used to further assess their pollution degree and potential
sources. Results showed that the surface sediments of Longjiang River have been
suffering heavy metal (As, Cd, Pb, Sb, and Zn) pollution to different degrees.
The maximum concentrations of As, Cd, Pb, Sb, and Zn were 67.0, 7.42, 227, 229,
and 807 mg.kg-1, respectively, while the Tl concentration were very low, with
little variation. Moreover, the polluted sites were mostly located in the mid
lower of the main stem and in tributaries (Dongxioajiang and downstream of
Dahuanjiang), and the pollution degree of the heavy metals, in a descending
order, were Cd > Sb > Zn > Pb > As > Tl. Pearson correlation analysis and PCA
indicated that As, Cd, Pb, Sb, and Zn predominantly originated from anthropogenic
inputs, including nonferrous metal mining and smelting, municipal sewage, and
agricultural activities, and Tl mostly derived from natural rock weathering. The
bioavailability of heavy metals in the sediments tended to be controlled by their
sources. The percentages of bioavailable heavy metals (As, Cd, Pb, Sb, and Zn) in
the highly anthropogenic impacted areas (the mid-lower of the main stem and
downstream of Dongxiaojiang tributary) were also high, with the average
percentages of bioavailable As, Cd, Pb, Sb, and Zn of 26%, 51%, 49%, 38%, and
47%, respectively. High EF values and high bioavailable percentages of heavy
metals easily and greatly cause high ecological risk of Longjiang River.
PMID- 29964839
TI - [Mechanism on Enhanced Nitrogen Removal in Municipal Secondary Effluent via
Internal-Electrolysis Constructed Wetlands at Low Temperature in Winter].
AB - Aiming at the low pollutant removal efficiency of constructed wetlands (CWs) at
low temperature in winter, three laboratory-scale vertical-flow CWs, namely
unplanted CWs, ordinary CWs, and internal-electrolysis CWs, were used to
investigate the nitrogen removal efficiency of municipal secondary effluent when
the water temperature was 3-12C. Moreover, the mechanism of enhanced
denitrification of the new wetland was revealed through analysis of the microbial
community diversity and community structure. The results showed that the internal
electrolysis CWs could make better use of the carbon sources in the municipal
secondary effluent and had a higher removal rate. The effluent TN concentration
was maintained at about (9+/-0.29) mg.L-1. The average TN removal rate was
42.27%, which was 17.91% and 17.33% higher than those of the unplanted CWs and
ordinary CWs, respectively. The microbial activity was detected using fluorescein
diacetate (FDA), and the result revealed that the microbial activity of the
internal-electrolysis CWs could reach 0.224 mg.g-1, which was 2.6 times and 3.4
times of that of the unplanted CWs and ordinary CWs, respectively. The microbial
denitrification intensity of the internal-electrolysis CWs was 2.8 times and 3.3
times of that of the unplanted and ordinary CWs, respectively. The results of
high-throughput sequencing showed that the microbial community diversity of the
internal electrolysis CWs was higher than those of the unplanted and ordinary
CWs. Denitrification microorganisms were detected, mainly Dechloromonas,
Rhizobium, Hyphomicrobium, and Rhodobacter, as well as Thiobacillus, which is an
autotrophic denitrifying bacterium. There were obvious advantages in the total
amount of denitrifying microorganisms in the internal-electrolysis CWs, as the
denitrification microorganisms accounted for 7.13% of the total microbial
biomass, which was 3.8 times and 8.7 times of that of the unplanted CWs and
ordinary CWs, respectively.
PMID- 29964840
TI - [Dynamic Replenishment Process of Nutrients in Tributary of Channel Reservoir].
AB - The process of phytoplankton succession and change in primary productivity are
directly determined by the seasonal variations in nutrients in tributary bays of
channel reservoirs. This study aimed at analyzing the effects of the main
nutrient sources on seasonal distribution of nutrients in Xiangxi Bay based on
the field data collected in 2010 and 2011. The tracing inorganic ions were Cl-
and Na+ that showed significant differences (P<0.01) between the mainstream and
the tributary. The nutrient contribution rates of different sources were
calculated by the binary linear model. The results showed that the nutrient
contribution rate of the mainstream was more than 75% during the dry season and
the impoundment period. The intrusion of the mainstream was the main source of
nutrients in Xiangxi Bay. The difference in the contribution rates between the
mainstream and the upstream decreased during the pre-flood drawdown period and
the flood season. The concentration of total phosphorus was higher in the
upstream, while the concentration of total nitrogen was higher in the mainstream.
The patterns of density currents were different and the nutrient contribution
rates of different sources changed accordingly. Therefore, the nutrients of
Xiangxi Bay changed regularly in different operation periods of the Three Gorges
Reservoir.
PMID- 29964841
TI - [Effect of the Rainfall on Extinction of Cyanobacteria Bloom and Its Mechanism
Analysis].
AB - There were three rainfall events with different intensity in the Xiangxi Bay
(XXB) from May 24 to June 2 in 2016. The factors such as hydrodynamics, water
temperature, optical properties, and chlorophyll a concentrations during the
rainfall events were analyzed. During the May 27 moderate rain period, the
upstream flow of the reservoir bay increased by 1.9 times and the average mixing
layer depth in the whole reservoir increased 8.2 m, compared to those before the
rainfall event. During the June 1 light rain period, the average mixing layer
depth in the whole reservoir increased 1.6 m and the average chlorophyll
concentration reduced 2.02 MUg.L-1, compared with those before the rainfall
event. During the June 2 heavy rain period, the upstream flow of the reservoir
bay increased by 4 times, the average mixing layer depth in the whole reservoir
increased 7.9 m and the average chlorophyll concentration reduced 14.64 MUg.L-1,
compared with those before the rainfall event. The algae moved from the upstream
to the downstream with water that reduced the concentration of algae in the XXB.
The water temperature stratification weakened during the rain event and the
average mixing layer depth in the whole reservoir increased, destroying the algal
growth environment. After the rainfall, under suitable light and temperature
conditions for 2-3 d, the water temperature stratification of the reservoir was
recovered and rapid growth and reproduction of algae occurred. As a result, the
chlorophyll concentrations in the reservoir increased. Rainfall has a periodic
inhibitory effect on the outbreak of algal blooms; however, it cannot
fundamentally solve the problem of tribal bay blooms.
PMID- 29964842
TI - [Relationship Between Macrophyte Communities and Macroinvertebrate Communities in
an Urban Stream].
AB - The channelization has caused severe degradation of aquatic ecosystems during the
past decades of rapid urbanization in metropolitan areas of China. The re
construction of the in-stream habitat of aquatic organisms and the restoration of
aquatic ecosystems were more difficult in the urban stream than in the natural
stream with the effluence of nutrient enrichment, water contamination, and in
stream habitat loss. Considering the ecological effects of the submerged
macrophyte replantation on macroinvertebrate communities, one of the urban
streams that used replantation restoration strategy was seasonally monitored from
October 2012 to July 2013. There were four sampling sites, two located at the
upper region and two in the middle region. Due to the relatively high levels of
organic matter contamination, there are no sites in the downstream region of
Qinghe River. Four types of submerged macrophyte were planted at each site to
restore the in-stream habitat of two years ago, including Potamogeton pectinatus,
Potamogeton crispus, Hydrilla verticillate, and Ceratophyllum demersum. Because
of the unexpected development, Myriophyllum spicatum and Acorus calamus appeared
at the upper reach of Qinghe River. Considering the average water depth of 30-40
cm, the revised Surber net with the enlarged net was used to collect
macroinvertebrate samples. At each sampling site, three replicates of
macroinvertebrates were carefully collected for each type of macrophyte. Three
replicates were sampled for the comparison at the imperviously concrete sections
of each site. The community composition of the macroinvertebrate was determined
by cluster analysis and ordination analysis. The density, biodiversity, and
community stability were higher in the sampling sections with the replantation of
macrophyte than in impervious concrete sections. The occurrence of intermediate
tolerant taxa such as Ephemera sp., Caenis sinensis Gui, Ecnomus sp., and
Hydropsyche sp. indicated the recovery and restoration of macroinvertebrates in
Qinghe River. However, the differences in the community structure, density, taxa
richness, biodiversity index, and the composition of functional feeding groups of
macroinvertebrates among different types of submerged macrophyte were not
identified. Unlike providing extra habitats for macroinvertebrates in the
vertical direction in natural streams and lakes, the submerged macrophyte
provided more stable benthic habitats in urban streams. The stem and leaf of
macrophytes could adjust the hydraulics and continually absorb, fix, and
accumulate the suspended solids in the sediment and water interface. The root
systems could stabilize the microhabitat of the sediment for macroinvertebrates,
benthic algae, and microorganisms. Those aquatic organisms played an important
role in the decomposition, transformation, and mineralization of nutrients and
organic matter in urban streams. Following the recovery of stabilized
microhabitats, community restoration and secondary succession of
macroinvertebrates could continually and slowly happen. This study improved the
understanding of the ecological effects of macrophytes on the restoration of
aquatic organisms and ecosystems in urban streams.
PMID- 29964843
TI - [Characteristics of Nitrogen and Phosphorus Output in Runoff and Rainfall Runoff
in Lanlingxi Watershed, Three Gorges Reservoir Area].
AB - The small watershed of an agroforestry system in the Lanlingxi watershed in the
Three Gorges Reservoir area was studied by performing continuous monitoring of
nitrogen and phosphorus output and concentrations and analyzing the changes in
the output of nitrogen and phosphorus in runoff and its response to different
rainfall conditions. The results showed that:1The total runoff loss was 50.92*104
m3 in this watershed during the rainy season, with 52.43 kg.hm-2 lost by total
nitrogen, including nitrate nitrogen (30.26 kg.hm-2) and particulate nitrogen
(21.61 kg.hm-2), and 0.06 kg.hm-2 and 0.10 kg.hm-2 lost by ammonium nitrogen and
total phosphorus; 2The distribution of rainfall has the characteristics of stage
and strong rainfall during the wet season was the main driving force of soil
nutrient output. Rainfall runoff contributed to 88% of total nitrogen loss and
90% of total phosphorus loss in the rainy season; 3The main path of nitrogen and
phosphorus loss in the rainy season was the surface runoff caused by rainfall,
accounting for 68% of total nitrogen loss and 74% of total phosphorus loss;
4Nitrate nitrogen concentrations showed a negative correlation with rainfall
runoff and the output was mainly distributed in the later runoff process.
Ammonium nitrogen and total phosphorus concentrations were positively correlated
with rainfall and both were mainly distributed in the early stage of the runoff
process; 5The concentrations of total nitrogen in this watershed exceeded the
standard values. The water quality in the rainfall and the non-rainfall period
was worse than Grade V.
PMID- 29964844
TI - [Screening Method of Priority Control Pollutants in Groundwater Based on
Contamination Assessment].
AB - Screening of priority control pollutants is an effective technical means for
environmental management and environmental quality protection. Quick and
efficient identification of pollutants is useful when attempting to prevent and
control groundwater pollution. In order to explore a screening system for a set
of priority pollutants that can be applied to regions with weak basic
information, a screening method of priority pollutants based on contamination
assessment is put forward in this paper. Based on the data of groundwater
detection and analysis, using the evaluation method for pollution index
classification, and combined with the pollution degree frequency score
superposition method. The screening method of priority control pollutants in
groundwater based on contamination assessment was established. This method was
applied to the screening of pollutants in groundwater in the city of Golmud in
Qinghai Province, China. The results were verified by using the screening system
based on risk assessment, and the differences in the two systems are discussed.
The results show that three categories of 10 kinds of chemical parameters,
including TDS, total hardness, chloride, sulfate, sodium, fluorine, total iron,
pyrene, phenanthrene, and aluminum, were determined as priority control
pollutants in the Golmud region. It was consistent with the results of the
screening method based on the risk assessment, and the screening results were
reliable. The method based on risk assessment is complex and requires additional
basic information, but it has certain foresight and is suitable for regions with
abundant basic data. The method based on contamination assessment is simple and
convenient and requires less abundant basic data. However, it is easily affected
by background values. It is more suitable for the screening of priority control
pollutants in regions with weak pollution source information.
PMID- 29964845
TI - [Effect of Sulfur to Quartz Sand Ratios on the Removal of High-Concentration
Perchlorate in Packed-Bed Reactors].
AB - Three autotrophic packed-bed reactors, each with a different sulfur/quartz sand
ratio(R1, 2:1; R2, 1:1; R3, 1:2,)were used to remove high-concentration
perchlorate from contaminated water. The perchlorate removal efficiency,
kinetics, and biofilm of the reactors were studied using different perchlorate
concentrations and hydraulic retention times (HRTs). The perchlorate removal
efficiency decreased with higher perchlorate concentration and shorter HRT, and
the removal efficiency of R1 was higher than of R2 and R3. The maximum removal
loading of R1 was 2.18 kg.(m3.d)-1at an HRT of 3.2 h and perchlorate
concentration of 300 mg.L-1. The half-order kinetics model fit the reactors'
experimental data well; the reaction rate constants of R1, R2, and R3 were 8.036,
6.596, and 4.212 mg1/2.(L1/2.h)-1. The yield of SO42- was greater than the
stoichiometric yield of sulfur autotrophic reduction owing to sulfur
disproportionation. The disproportionation was inhibited with a higher
perchlorate concentration or shorter HRT. Moreover, disproportionation of R3 was
the weakest because the SO42- yield of R3 was lower than of R1 and R2. The pH and
alkalinity of the effluent increased with lower perchlorate concentration and
shorter HRT. The development of biofilm in R2 and R3 was better than in R1. The
secretion of extracellular polymeric substances can promote the formation of
biofilm.
PMID- 29964846
TI - [Adsorption of Methylene Blue and Cu(II) by Activated Carbon/Macromolecule
Composite Hydrogel].
AB - Activated carbon/alginate/poly(vinyl alcohol) composite macromolecule hydrogels
(CAP) were prepared as adsorbents to study their adsorption performance for
methylene blue (MB) and Cu2+ in aqueous solution. The effect of dosage, pH,
temperature, contact time, and initial concentrations of MB and Cu2+ on the
adsorption process was investigated. SEM, FTIR, and BET analyses were conducted
to identify the physicochemical properties of CAP. The results indicated that
activated carbon was successfully loaded into the interconnected 3D porous
network and CAP had rich -COOH and -OH groups. The surface area of the composite
hydrogel was 112.7 m2.g-1. With the dosage and temperature increase, the adsorbed
amount of MB and Cu2+ on CAP decreased, while with the increase in pH, the
adsorbed amount increased. The adsorption isotherm was fitted to the Langmuir
equation and the maximum monolayer adsorption capacities of MB and Cu2+ on CAP
were 1940.75 and 190.48 mg.g-1, respectively. The adsorption was a fast process
and 90% of the maximum adsorption capacity could be reached in 5 h. The kinetic
data were fitted to the pseudo-second-order kinetic model reasonably well. CAP
had excellent adsorption properties after five times of regeneration.
PMID- 29964847
TI - [Adsorption Performance and Mechanism of HZO@SGH for the Removal of Fluoride from
Aqueous Solution].
AB - Three-dimensional porous composites based on hydrous zirconium oxide and self
assembled graphene hydrogels (HZO@SGH) were successfully synthesized via
homogeneous precipitation. HZO@SGH was characterized by X-ray diffraction (XRD),
scanning electron microscopy (SEM), Fourier transform infrared spectroscopy
(FTIR), and X-ray photoelectron spectroscopy (XPS) to investigate the morphology
and the defluoridation mechanism. The adsorption performance and mechanism of
HZO@SGH for fluoride was investigated via batch adsorption experiments. The
results revealed that the adsorption capacity of HZO@SGH for fluoride was
obviously higher than that of HZO or SGH singly. The adsorption data for fluoride
onto HZO@SGH complied with the pseudo-second-order kinetic model, indicating that
the adsorption rate was mainly controlled by chemical adsorption. The adsorption
process could be described well with the Dubinin-Radushkevich isotherm model, as
the maximum adsorption capacity was approximately 31.79 mg.g-1, which is higher
than that of some zirconium-containing adsorbents, as previously reported.
HZO@SGH showed excellent adsorption properties in the fluoride solution contained
NO3-, Cl-, and a low concentration of SO42- (<= 10 mg.L-1) at low pH (3-6.5). The
preparation of HZO@SGH was convenient and environmentally friendly, as it was
easily separated from the fluoride solution and did not cause secondary
pollution. Hence, the prospect of HZO@SGH in practice was brilliant.
PMID- 29964848
TI - [Mechanism of MgO/GAC Catalyzed Ozonation of Organic Compounds].
AB - MgO/granular activated carbon (MgO/GAC-1) was prepared via an impregnation
method, and its activity in ozonation of diuron and acetic acid was investigated.
MgO/GAC-1 was also compared in stability to the same catalyst prepared via
precipitation according to the literature (MgO/GAC-2). The results showed that
MgO/GAC-1 could increase efficiency of ozonation by 15%-35% in the process of
degradation of diuron and acetic acid. When the pH of the solution was neutral or
alkaline, MgO/GAC-1 could effectively retard the decrease in pH owing to
formation of small molecular organic acids, thus ensuring the efficiency of
ozone. When the pH of the solution was acidic, MgO/GAC-1 could increase the pH of
the solution to a certain extent, thereby enhancing the efficiency of ozonation.
The adjusting effect of pH value is the reason why MgO can significantly improve
the efficiency of ozonation, a fact that was ignored in the relevant literature.
Although MgO/GAC-1 had a larger specific surface area, MgO/GAC-1 had better
activity in ozonation. A recycling test also indicated that MgO/GAC-1 had better
stability, showing a good prospect for application.
PMID- 29964849
TI - [Ozonation Characteristics of Low Coagulability Organic Matter from the Secondary
Effluent of WWTPs].
AB - The aim of this study was to investigate the effectiveness of ozonation on the
removal of organic matter with low coagulability from municipal secondary
effluent. The results revealed that the removal efficiency of coagulation
generally remained quite low. The residual organic matter belonged to low
coagulability organic matter. The presence of the ozone increased the removal
efficiency of color and UV254 gradually for low coagulability organic matter,
whereas DOC had no noticeable change; the efficiencies were 45%, 34%, and 20%,
respectively, at a dosage (denoted as O3/DOC) of 1.5 mg.mg-1. It could be
concluded that ozone easily reacted with unsaturated organic matter, and the
mineralization of organic matter was less effective. In order to further define
the variation in organic matter of the secondary effluent, the differences
between the relative molecular weight distribution and fluorescence
characteristics of coagulation and ozonation with different zone dosages were
monitored in this study. The findings showed that coagulation had little effect
on organic content. Nonetheless, ozone might have preferentially reacted with
high-molecular-weight substances of organic matter with low coagulability and
reduced the fluorescence intensity in the humic-like regions significantly. The
shift of fluorescence peak was not changed by ozonation. In addition, via X-ray
photoelectron spectroscopy (XPS) analysis, it was identified that coagulation
could remove carboxylic organic matter. On the other hand, with the increasing
ozone dosage (from 0 to 1.5 mg.mg-1), ozone could preferentially react with low
coagulability organic matter with aromatic structure, thus the amount of
aliphatics increased gradually.
PMID- 29964850
TI - [Quantitative Analysis of Dominant Pollutants in Secondary Effluent via Dye Probe
Technology].
AB - The linear relationship between the concentration of either bovine serum albumin
(BSA) or sodium alginate (SA) and the intensity of a resonance light scattering
(RLS) spectrum was established by using Congo red and neutral red as the dye
probes, respectively. Moreover, the linear relationship between the concentration
of humic acids (HA) and UV absorbance was determined by using toluidine blue (TB)
as the dye probe. The detection of concentration range and the pH value of three
kinds of standard substances were optimized. The recovery rate of bi-and tri
element samples of the standard objects was investigated by means of the dye
probe analysis method. The results show that, in the appropriate concentration
range, the linear correlation coefficients between the concentration of BSA, HA,
or SA and the intensity of its corresponding dye probe spectrum were all high, at
0.98. The recovery rates of the three kinds of standard objects in mixed samples
were all greater than 95%, and the standard errors were all less than 0.11%.
Based on qualitative analysis of the proteins, polysaccharides, and humic acids
in the secondary water discharge samples of urban sewage obtained via UV and RLS
spectra, the dominant pollutants were confirmed in the four kinds of secondary
effluent. The relative deviations of the concentration of polysaccharides and
proteins measured using the dye probe technique and the national standard method
ranged were from 1.2% to 0.04%.
PMID- 29964851
TI - [Lab-scale ANAMMOX Process in a Wastewater Treatment Plant].
AB - A lab-scale, completely anaerobic ammonium oxidation (ANAMMOX) process was
operated in a municipal wastewater treatment plant (WWTP). Sewage effluent
treated by an A/O process and nitrification process was input as the substance to
start up the up-flow ANAMMOX filter reactor. After the 109th day, the ammonia
removal rate and nitrite removal rate were greater than 90% for 15 successive
days and the nitrogen removal rate was higher than 70%. The ANAMMOX filter
reactor successfully started up. From days 245 to 333, the reactor was running
during the winter. The weight of biomass reached 12.24 mg.g-1, and the average
nitrogen removal rate was 54.3%. Backwash was adopted at day 461, and the weight
of biomass decreased to 8.01 mg.g-1. From days 605 to 693, the reactor was
running in the winter again. The weight of biomass was 10.41 mg.g-1, and the
average nitrogen removal rate was sustained at 69.7%. Compared with the previous
winter, the weight of biomass was lighter but the total nitrogen removal loading
was 23% greater. For the entire operation, the ANAMMOX rate at high temperature
was stable but that at low temperature increased from 1.5 kg.(kg.d)-1 to 3.6
kg.(kg.d)-1. The results show:Long-term domestication at low temperature was in
favor of improving treatment efficiency of ANAMMOX process in cold environment
and realized ANAMMOX process operated efficiently in winter.
PMID- 29964852
TI - [Effect of Aeration Rate on Shortcut Nitrification Recovery in Intermittent
Aeration Mode].
AB - Shortcut nitrification sludge, which was set aside for two months, was recovered
using Reactors I, II, III, and IV. The aeration rates of Reactors I, II, III, and
IV were 120, 100, 80, and 60 L.h-1, respectively, while treating real domestic
sewage, and the ratio of aerobic/anoxic was 30 min/30 min at the temperature of
25C. The influent of ammonia was 50-80 mg.L-1, and the concentration of effluent
ammonia was stable, at below 5 mg.L-1, after the 12th, 18th, 21st, and 21st
cycles. The removal ratio of ammonia nitrogen was about 95%. The highest
concentrations of nitrite for Reactors I, II, III, and IV were 20.83, 22.81,
21.50, and 20.73 mg.L-1, respectively, which occurred in the 30th, 35th, 38th,
and 42nd cycles, respectively. The concentrations of effluent nitrate were lower
than 0.5 mg.L-1, and the nitrite accumulation rates were higher than 99%. The
activity of ammonia-oxidizing bacteria (AOB) increased gradually and finally
stabilized at 100.00%; however, the activity of nitrite-oxidizing bacteria (NOB)
was gradually inhibited. The recovery of shortcut nitrification was achieved
successfully in the different aeration modes.
PMID- 29964853
TI - [Effect of Aerobic/Phosphorus Granules on Start-up of Partial Nitrification
Granular Sludge].
AB - The different effects of additional aerobic granules (AGs) and phosphorus removal
granules (PRGs) on the start-up and stable operation of partial nitrification
granular sludge (PNGS) were compared at room temperature(22-28C). The results
showed that in the first stage (days 0-22), partial nitrification was
accomplished on day 19 for the three reactors (R1, R2, and R3). In the second
stage (days 23-56), 20% AGs and 20% PRGs were added to R2 and R3 to induce PNGS.
The start-up of the granules of the three reactors was successfully achieved. The
mean particle sizes of R1, R2, and R3 reached 412 MUm at day 76, 468 MUm at day
42, and 400 MUm at day 56. In the third stage (days 57-108), because the influent
ammonia load increased from 0.4 kg.(m3.d)-1 to 0.5 kg.(m3.d)-1 and the COD load
increased from 0.2 kg.(m3.d)-1 to 0.5 kg.(m3.d)-1, the mean particle sizes of R1
and R2 increased significantly. The average particle sizes of R1 and R2 reached
689 MUm and 893 MUm by the end of the operation (day 108), but sludge expansion
occurred in R3. The inoculation of either AGs or PRGs could quickly achieve
granulation, but the PNGS inoculated with the AGs could adapt to higher C/N and
be more tolerable to shock loads and long-term stable operation.
PMID- 29964854
TI - [Microbial Communities and Sludge Specific Resistance in Two SBRs Treating
Leachate].
AB - The relationship between microbial populations and sludge filtration performance
was studied when active sludge was used to treat the leachate from municipal
solid waste incineration plants. Two SBRs (SBR1 and SBR2) were operated at the
same conditions, except that SBR1 was exposed to the sunlight and SBR2 was in the
dark. To identify the difference in microbial populations in two reactors, high
throughput sequencing method was used. On the 50th day, the fungi abundance in
SBR2 was higher than in SBR1. Phylum Rozellomycota became the dominant fungi in
SBR1, whose relative abundance was 83.71%. Phylum Basidiomycota and Genus
Trichosporon became only dominant fungi in SBR2, whose relative abundances were
99.84% and 99.78%, respectively. Bacterial abundance in SBR1 was higher than in
SBR2. In SBR1, Thauera was the major bacterial genus, whose relative abundance
was 39.35%. In SBR2, Planktosalinus, Thauera, and Ottowia were the major
bacterial genera, whose relative abundances were 16.84%, 16.23%, and 12.55%.
Rotifers and other predatory metazoan were detected on the 30th-50th days in SBR1
and sludge specific resistance began to decline on the 35th day. Filamentous
fungi bulking caused by Trichosporon resulted in a continuous increase in sludge
specific resistance of SBR2. The dominant microbial communities (especially
fungi) and sludge specific resistances in SBR1 and SBR2 were very different
because of the effect of sunlight. Therefore, sunlight plays an important role on
microbial communities and sludge characteristics.
PMID- 29964855
TI - [Sources and Risk Assessment of Polycyclic Aromatic Hydrocarbons from the
Urbanization Process of Topsoil].
AB - To study the effects of urbanization on concentration, sources, and health risks
of polycyclic aromatic hydrocarbons (PAHs), 95 topsoil samples were collected
from Liaoning Province. For this assessment, 21 PAHs were analyzed via gas
chromatography-mass spectrometry and discussed. The results show the total
concentrations of the 21 PAHs in background, Shen-Fu, Shen-Yang, and Fu-Shun were
1496.76 MUg.kg-1, 3000.50 MUg.kg-1, 8705.11 MUg.kg-1, and 8178.90 MUg.kg-1,
respectively, which is positively correlated with the urbanization levels.
Diagnostic ratios and PMF modal analysis indicate that the sources of the PAHs in
soils were most likely coal combustion and traffic combustion (petroleum
combustion). The main sources of PAHs in the four areas were petrochemical
combustion (41.0%), coal combustion (64.4%), traffic combustion (67.5%), and
traffic combustion (62.0%), that is, with the urbanization process, human
activity (mainly traffic combustion) gradually become the major contributor of
PAHs to the environment. Health risk assessment showed that the risk of cancer
exposure through soil digestion and skin exposure was higher. There is a higher
health risk from PAHs in urban soils, and the health risks associated with
children and adolescents are greater than with other residents, requiring more
attention.
PMID- 29964856
TI - [Spatial Variability and Contamination of Arsenic in Soils of Xijiang River
Basin].
AB - In this study, 2585 soil samples were collected in the Xijiang River Basin in
Guangxi Zhuang Autonomous Region and the spatial variability and contamination of
Arsenic in soils were evaluated using geostatistical and GIS tools. The results
showed that the concentrations of As in surface soils (23.82 mg.kg-1) were higher
than the background values of the Guangxi and Xijiang Rivers in natural soils;
the upstream values (Diaojiang River and Huanjiang River) (30.22 mg.kg-1) were
significantly higher than those in other regions. Concentrations of As in soil
samples were in the order of soil in mining areas > soil in dryland > natural
soil > paddy soil. As in mining areas were significantly higher than in other
areas; high As concentrations were measured in the upstream of the Diaojiang
River basin and the downstream of the Huanjiang River Basin. Low concentration
clusters were in the six villages of Nandan, which are far from the mine, and in
the upper reaches of the Dahuanjiang River and Xiaohuanjiang River Basin. Spatial
autocorrelations of arsenic in the watershed soil were evident and the structural
variability was dominant. The concentration of As in the upper reaches decreased
from the northwest to the southeast. High As concentrations were distributed
naturally along the river basin; concentrations in the middle and lower reaches
of the basin were between 0.44 mg.kg-1 and 40 mg.kg-1. The concentration levels
of As in total soil samples ranged from no-pollution to slight pollution, and the
pollution was mainly distributed in the administrative areas of the city and the
intensive areas of mining activities, among which the soil pollution in
Jinchengjiang River and Nandan counties was more prominent. Effective measures
should be taken to strengthen the safety level of tailings reservoirs during the
rainy season, so as to maintain the production levels while protecting living
standards of local residents.
PMID- 29964857
TI - [Characterization of Phosphorus in Urban Surface Soils in Kaifeng City and Its
Risk of Loss].
AB - Characterization of phosphorus (P) and its risk of loss in urban soils in Kaifeng
City, Henan Province were studied through field sampling and laboratory
experiments. The spatial distribution of P and the map of risk of loss were
obtained using geostatistical and spatial analysis techniques. The P content in
urban soils ranged from 400 to 1427 mg.kg-1, the proportions of inorganic P in
total P ranged from 65% to 99%, and Olsen-P and CaCl2-P in soils were 3.41-115.03
mg.kg-1 and 0.01-9.40 mg.kg-1, respectively. The composition of P was consistent
in different urban areas and P concentrations were higher in residential areas.
Spatial variations in P concentrations in soils were significant; the
concentrations of P in eastern Kaifeng City were higher than those in western
Kaifeng and the highest concentrations were detected in central Kaifeng. Olsen-P
can be used as an indicator of the leaching risk of soil P. The critical value of
leaching P from the soil was 22.18 mg.kg-1 and the concentration of Olsen-P in
33.64% of urban soil samples exceeded the critical value. The highest risk of P
loss existed in central Kaifeng City.
PMID- 29964858
TI - [Distribution Characteristics and Health Risk Assessment of Heavy Metals in a
Soil-Rice System in an E-waste Dismantling Area].
AB - This study selected Guiyu Town, Guangdong Province as the research area, the
content of 15 kinds of metals (As, Be, Cd, Co, Cr, Cu, Hg, Li, Mn, Ni, Sb, Sn,
Pb, V, and Zn) in the soil was determined, and the content of heavy metals (As,
Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the rice of this research area was identified.
Multivariate statistical analysis and a human health risk assessment model were
used to investigate the distribution characteristics and health risk of heavy
metals in a soil-rice system. The results showed that Hg, Sb, and Sn in the
surface soil surrounding the electronic waste dismantling area have obvious
accumulation effect. The average content of Cd and Hg exceeds the II standard
limit of the "Environmental Quality Standard for Soil" (GB 156182-1995), and that
Guiyu Town is more seriously polluted than Chendian Town and Simapu Town. The
multivariate statistical analysis showed that Cu, Sb, Ni, Zn, Sn, Pb, and Hg
originated from the surrounding electronic waste dismantling activities, Cd and
Be originated from other man-made sources of pollution, and V, Li, Cr, Co, As,
and Mn originated from natural sources. Heavy metal evaluation concentration in
the soil-rice system by heavy metal migration accumulated in rice are in
compliance with national food hygiene standards, and the enrichment ability is Cd
> Zn > Cu > Ni > As > Cr > Hg > Pb. Soil heavy metal health risk assessment
results showed that children are more susceptible to heavy metal pollution, and
handling-oral ingestion is the main way of soil exposure risk. The non
carcinogenic risk and carcinogenic risk of heavy metals in the soil of each town
are acceptable. The health risk in Guiyu Town through ingestion of rice is mainly
from the elements that include As, Cr, Cu, and Ni.
PMID- 29964859
TI - [Residue Levels and Health Risk Assessment of Organochlorine Pesticides in Rice
from Shanghai].
AB - As one of the main producers and consumers of pesticides in the world, China has
historically used large quantities of organochlorine pesticides, such as DDT and
HCH. Rice is a staple food crop in Shanghai, where the Qingpu and Chongming
districts are two important rice planting areas. This study detected the residue
levels of 24 organochlorine pesticides (OCPs) in rice samples collected from
Qingpu and Chongming in Shanghai. The composition and health risk of OCPs in rice
samples were investigated. The results revealed that DDTs and HCHs were the main
OCPs in rice from the study area. The mean levels of 24 OCPs residues in rice
from Qingpu and Chongming were 6.53 ng.g-1 and 4.70 ng.g-1, respectively. The
analyses of all the target compounds met the China National Food Safety Standard.
The concentrations of 4,4-DDE and beta-HCH were the highest in rice from Qingpu,
while 2,4-DDT and beta-HCH were the main components in rice from Chongming.
Source analysis showed that dicofol and lindane might be still used recently in
some areas of Shanghai. The health risk assessment results indicated that there
was no obvious risk to human health by eating rice from Shanghai based on the
OCPs studied.
PMID- 29964860
TI - [Effects of Tetracycline Antibiotics on Growth and Characteristics of Enrichment
and Transformation in Two Vegetables].
AB - Pot experiments were carried out to study different levels (0, 50, and 150 mg.kg
1) of three tetracycline antibiotics[tetracycline (TC), oxytetracycline (OTC),
and chlortetracycline (CTC)] on the growth, concentration of tetracycline
antibiotics, and their characteristics of enrichment and transformation in two
kinds of vegetables (lettuce and Chinese cabbage). The results showed that the
fresh weight of shoots and roots of lettuce decreased by 1.56%-26.84% and 17.36%
51.04%, respectively, when exposed to tetracycline antibiotics compared to the
control, while the fresh weight of shoots and roots of Chinese cabbage increased
by 3.7%-7.3% and 3.1%-82.2%, respectively. The stomatal conductance (Gs) and
transpiration rate (Tr) of lettuce and cabbage increased when exposed to
tetracycline antibiotics, while the net photosynthetic rate (Pn) of lettuce
decreased by 32.43%-82.43% at 150 mg.kg-1 of TC compared to the control. Compared
to the control, the activities of SOD in lettuce and cabbage decreased 29.17%
223.12% when exposed to tetracycline antibiotics, and the lowest activities of
SOD in lettuce and cabbage were found in OTC treatments. The highest content of
MDA in lettuce and cabbage was observed at 150 mg.kg-1 of TC (except for lettuce
leaves). The contents of tetracycline antibiotics in the shoots and underground
portions of Chinese cabbage were higher than that of lettuce, and higher contents
of tetracycline antibiotics in vegetables were found with the CTC treatments. The
residual amount of antibiotics in lettuce soil was higher than that in the
Chinese cabbage soil, and the highest residual amount in the soil was observed
with the OTC treatment. The bioconcentration factors (BCF) and transport factor
(TF) of Chinese cabbage were, respectively, 1.07-7.35 and 1.15-2.25 times that of
lettuce. OTC and CTC were more easily concentrated in the two vegetables.
Therefore, OTC and CTC may bring a higher ecological risk.
PMID- 29964861
TI - [Bioavailability of Silicon Fertilizer Coupled Water Management on Soil
Bioavailability and Cumulative Control of Rice in Compound Contaminated Paddy
Soils].
AB - The effect of wet irrigation (CK), agronomic measure flooding (WF), instantaneous
silicon fertilizer combined with flooding measures (FYsi), mineral silicon
fertilizer combined with flooding measures (FKsi), and a mix of two kinds of
silicon fertilizer combined with flooding measures (FYK) on the bio-availability
of As and Cd in soil and the accumulation of As and Cd in rice were investigated
by pot experiments. The results showed that the pH of the soils combined with
flooding measures was increased by 0.12-0.72 units with similar trends of an
increase and then a decrease before finally become neutral. The Eh of the soil
combined with flooding was significantly decreased, but the Eh of soil after
flooding treated by FYsi, FKsi, and FYK combined with the flooding was
significantly higher than that treated by WF, and the content of Cd in brown rice
was reduced by 38.83%-65.05% compared with that treated by CK. The WF and FYK
treatments can significantly reduce the accumulation of Cd in brown rice,
resulting in the lowest Cd contents in brown rice of 0.98 and 0.72 mg.kg-1,
respectively. The contents of As in brown rice treated by FYsi, FKsi, and FYK
were decreased by 23.80%, 38.10%, and 47.62%, respectively, compared with that
with the CK treatment, except that the content of As in brown rice treated by WF
increased by 36.64%. FYsi and FYK treatments had the best inhibitory effect on
the accumulation of As in brown rice, with the lowest As contents of 0.13 mg.kg-1
and 0.11 mg.kg-1 in brown rice (P <0.01), respectively. There was an extremely
significant correlation between the contents of extractable Cd and the total
content of Cd in the brown rice (P <0.05), and there was no significant
difference between the contents of extractable As and the total content of As in
the brown rice. Therefore, FYsi, FKsi, and FYK can effectively inhibit the
accumulation of Cd and As in rice grown in Cd-As compound polluted soil, and FYK
showed the best performance.
PMID- 29964862
TI - [Liver and Kidney Function of E-waste Dismantling Workers and Potential
Influencing Factors].
AB - High levels of exposure to heavy metals and persistent organic pollutants (POPs)
by e-waste dismantling workers has attracted increasing attention, but the health
conditions of the workers are seldom reported. The liver and kidney functions of
the workers were studied by comparing the blood indicators of the worker group
with those of the control group. Moreover, factors affecting the liver and kidney
functions, such as the sexuality, age, and working time, were identified using
correlation analysis. The ratio of aspartate transaminase and alanine
aminotransferase (AST/ALT) and the direct bilirubin (DBIL) of the workers were
significantly lower than the control group but the abnormal rate of liver and
kidney remained the same in both groups. The abnormal rates of liver and kidney
were higher in men than in women. ALT, AST/ALT, and urea nitrogen (BUN) increased
with age while creatinine (CREA) increased with working time. The factors of
liver and kidney damage caused by POPs and DBIL can be used as the indicators of
the damage caused by multi-factors.
PMID- 29964863
TI - [Application of a Two-stage Virtual Impactor in Measuring of PM10 and PM2.5
Emissions from Stationary Sources].
AB - Recently, the Ministry of Environmental Protection of China started the
development of emission inventories in fifteen Chinese cities. It includes the
esmission of PM10 and PM2.5 from stationary sources. However, there is no
national standard method in China for stationary source PM10 and PM2.5 sampling.
In this study, a two-stage virtual impactor was developed for sampling PM10 and
PM2.5 from stationary sources. Its performance was evaluated for four types of
sataionary sources, i.e., coal-fired power plant, waste incineration, circulating
fluid bed, and converter steelmaking. These four tested emission sources were
equipped with high efficiency PM control devices. PM2.5 mass concentrations
measured in the chimneys of these emission sources were (0.93+/-0.03), (3.3+/
0.65), (0.59+/-0.04), and (0.15+/-0.04) mg.m-3, respectively, while
the PM10 mass concentrations were (1.13+/-0.11), (6.9+/-0.86), (1.12+/-0.16), and
(0.43+/-0.15) mg.m-3, respectively.
PMID- 29964864
TI - [Hygroscopic Properties and Closure of Aerosol Chemical Composition in Mt. Huang
in Summer].
AB - The hygroscopic properties of aerosol have significant impact on aerosol optical
properties, cloud condensation nuclei activity and human health. Aerosol
particles growth factor and size-resolved ions chemical compositions were
monitored in Mt. Huang. The hygroscopic properties of aerosol particles in Mt.
Huang were studied. The results demonstrated that between 70 nm and 230 nm, the
mass fractions of (NH4)2SO4, organic matter and other insoluble materials were
the highest. The fraction of NH4NO3 standed in the medium. The fraction of
NH4HSO4 was the lowest. The fraction of inorganic salts increased with increasing
particle diameter. Aerosol particles during daytime had stronger hygroscopicity
than that at night and the hygroscopicity of aerosol became stronger when its
diameter increased. The calculation hygroscopic parameter kappa of aerosol
particles showed similar diurnal variation characteristics to the observation
kappa. Good closure could be achieved when ZSR mixing rule was used based
on aerosol chemical composition to calculate aerosol hygroscopic parameter
kappa and the coefficient of determination was 0.60 for all the diameters.
PMID- 29964865
TI - [Characteristics of Water-soluble Inorganic Ions in Atmospheric Aerosols in
Shenyang].
AB - To investigate the levels and seasonal variation of water soluble inorganic
components in ambient aerosol in Shenyang, 25 samples were collected with
Andersen cascade sampler from Jun. 2012 to May. 2013 and nine water-soluble ions
in samples were analyzed by IC. The different characteristics of aerosols between
clean and pollution days in winter were discussed based on these samples. The
results showed that the annual concentrations of total water soluble inorganic
ions were 22.30 MUg.m-3 and 14.29 MUg.m-3 in fine and
coarse particles, and SO42- and Ca2+ were the most abundant
ions, respectively. The ratio of mass concentration between SO42- and
NO3- was 2.28 and the NH4+ existed in the form of (NH4)2SO4
and NH4NO3 in fine particles. The concentrations of total water soluble ions in
fine particles were higher in winter and spring compared with those in summer and
autumn, and they varied significantly between different seasons. The fossil fuel
consumption led to the maximum values of secondary inorganic ions in fine
particles during winter. The concentrations of total water soluble ions in coarse
particles varied slightly though they were higher in autumn and lower in winter,
and the wind-drifting sand was responsible for the higher concentration of
Ca2+ in autumn in coarse particles. The concentration of SO42
, NO3-, NH4+ accounted for 80% of total water soluble
inorganic ions during clean days and rose to 94% during pollution days. The ions
were mostly concentrated in the size ranges of 0.43-0.65 MUm and 0.43-2.1 MUm
respectively during clean and pollution days in fine mode. The peaks of SO42
, NO3-, NH4+ in fine mode shifted from 0.43-0.65 MUm
to 1.1-2.1 MUm, which meant these ions were transformed from condensing mode to
droplets mode during pollution days. The air mass produced at Lake Baikal and
transported through high altitude to the sampling point caused clean days,
however the air mass transported through industrial areas might bring pollutions
to the sampling point then caused pollution days.
PMID- 29964866
TI - [Characteristics and Source Apportionment of Water-soluble Ions in Dry Deposition
in the Summer and Autumn of Nanjing].
AB - A total of 84 effective dry deposition samples were collected from July to
October, 2014 in Nanjing, and the chemical composition and source apportionment
of water-soluble ions dry deposition in the summer and autumn season were
discussed. The results indicated that the average pH was 6.2, and the dry
deposition samples usually appeared neutral. Ca2+ and NH4+
were the major cations and their average daily concentrations were 115.7
MUeq.L-1 and 31.2 MUeq.L-1,accounting for 68.3% and 18.6%
of total cations, respectively. SO42-, Cl- and NO32
were the main anions, and their average daily concentrations were 30.4,
20.7 and 18.7 MUeq.L-1, a total of 89.2% of the total anions,
respectively. High temperature and humidity of meteorological factors and
contaminated air mass affected dry deposition. Local air mass had greater impact
on dry deposition pollution, which indicated that dry deposition pollution had
local property. In summer and autumn seasons in Nanjing, the stationary sources
had more contributions to atmospheric dry deposition of water-soluble ions than
mobile sources, while the environmental control measures for the Nanjing Youth
Olympic Games had greater effect on stationary sources than mobile sources.
Studies of the origins of major ions indicated that SO42- and
NO32- were mostly attributed by the anthropogenic activities, and
Cl- was mainly from ocean sources, while K+ and
Mg2+ were mostly from the terrestrial input.
PMID- 29964867
TI - [Distribution Characteristics of Water-soluble Ions in Size-segregated
Particulate Matters in Taiyuan].
AB - The distributions of size-segregated particles (PM10) and water-soluble ions
(WSIs) in Taiyuan were studied from July 2014 to April 2015 by TE-235 aerosol
sampling and ion chromatography analyzing. As the results shown, the daily PM10
level was 173.7 MUg.m-3, which exceeded the Grade II limitation value
in the Ambient Air Quality Standard (150 MUg.m-3, GB 3095-2012). PM10
levels varied seasonally, and its were 199.1 and 194.2 MUg.m-3 in
winter and spring, respectively, which were much higher than those in summer. The
PM10 size-segregated was bimodal distribution for the range of 0-0.95 and 3.0-7.2
MUm. The concentration of WSIs was the highest in winter, followed by summer and
spring. SO42-, NO3- and NH4+ were the main water
soluble ions and accounted for 66% to 80% of the total WSIs. SO42-,
K+, NH4+ and Cl- showed a unimodal distribution
at <0.95 MUm in all samples, while Ca2+ and Mg2+ showed a
bimodal distribution at <0.95 MUm and 3.0-7.2 MUm. NO3- showed a
unimodal size distribution at <0.95 MUm in winter and spring, compared with a
bimodal distribution at <0.95 MUm and 3.0-7.2 MUm in summer. By the correlation
analysis, PM10 and WSIs decreased with the increase of wind speed in summer and
winter other than in spring for the road-dust re-suspension by strong wind. Based
on the ratio analysis of NO3-/SO42- and
Mg2+/Ca2+, coal combustion was the main source of NO3
and SO42-, while Mg2+ and Ca2+ were
mainly from the dust and coal combustion.
PMID- 29964868
TI - [Characteristics of Ozone over Standard and Its Relationships with Meteorological
Conditions in Beijing City in 2014].
AB - The spatial-temporal distribution characteristics of O3 and the correlations
between O3 and meteorological elements in Beijing urban area were investigated
based on the hourly O3 monitoring data from January to December in 2014 released
by Beijing Municipal Environmental Monitoring Center. The annual concentration of
O3 in Beijing was about 56.18 MUg.m-3 in 2014. In the over polluted
days during May and September, the O3 concentration could reach as high as 148.05
MUg.m-3. The diurnal distribution of ozone presented a clear unimodal
pattern with its peak appearing at 15:00 or 16:00 and trough at 06:00 or 07:00
and the concentrations of O3 during 09:00 and 23:00 was significantly higher than
those in the Summer time. For the spatial distribution of O3, the concentration
was lower in central urban area with the highest concentration appearing at plant
garden site in the west of the urban area. Ground weather type of O3 over
polluted days was divided into three categories including high-pressure, low
pressure, equalizing field, which accounted for 16%, 36%, 48%, respectively. The
concentration of O3 was negatively correlated with the air pressure, humidity and
visibility while it was positively correlated with the wind speed and
temperature. In one heavy pollution episode of O3 caused by local photochemical
pollution and regional transport from May 29th to June 1st in 2014 in Beijing,
regional transport showed a very important influence on the concentration of O3
in Beijing.
PMID- 29964869
TI - [Chemical Composition of Alkanes and Organic Acids in Vehicle Exhaust].
AB - The soot of 11 diesel buses and 20 gasoline cars was sampled by direct sampling,
and the main organic compounds of the samples were separated and qualitatively
analyzed by GC-MS. The results showed that the mass fraction of n-alkanes
was 1.31-149.08 MUg.g-1 and 15.35-556.03 MUg.g-1. The main
carbon number of n-alkanes in diesel buses and gasoline cars soot was 20
and 29, respectively, and gasoline cars generated more long chain alkanes with
high boiling point. The total mass fraction of pristane and phytane in diesel
buses was 15.24 MUg.g-1 and 21.79 MUg.g-1, respectively,
while the two values in gasoline cars were 2.31 MUg.g-1 and 2.69
MUg.g-1, respectively. The ratios of pristane and phytane were 0.6994
and 0.8587, and the ratios of phytane and octadecane were 0.3565 and 0.7472. The
changes of the relative mass of fatty acids were relatively large, the change
ranges in buses and cars were 0.01-40.87 MUg.g-1 and 3.8-113.7
MUg.g-1, respectively, and the organic acid with the highest content
in the buses was 3- hydroxybutyric acid.The maximal ratio of hexadecanoic acid
and butanedioic acid (C3/C4) was 5.93. The most abundant n-alkanes in gasoline
cars soot was C16, and the mass fraction of aromatic acids was 5.05-31.70
MUg.g-1 and 0.1-228.38 MUg.g-1, respectively.
PMID- 29964870
TI - [Effect of DOC/CCRT Aging on Gaseous Emission Characteristics of an In-used
Diesel Engine Bus].
AB - Based on heavy chassis dynamometer, an experimental study was conducted in diesel
bus with China Stage III, which investigated the effects of gaseous emission
characteristics under CCBC driving cycle, such as carbon monoxide (CO), total
hydrocarbons (THC), nitric oxide (NO), nitrogen dioxide (NO2), nitrogen oxides
(NOx) and carbon dioxide (CO2) with the fresh/aged oxidized catalyst (DOC)
and oxidation catalysts coupled catalyzed particulate trap (DOC+CDPF, referred
CCRT). The results showed that using fresh and aged DOC/CCRT, the diesel bus
could reduce CO, THC and NO emissions, meanwhile increase NO2 emissions, but
NOx and CO2 emissions remained basically unchanged. In idle speed,
acceleration, deceleration and constant speed of working conditions, the diesel
bus using the fresh DOC had better oxidation efficiency of the CO and THC
emissions than the bus using the aged DOC. The diesel bus using the fresh CCRT
had higher oxidation efficiency of THC emissions, but lower oxidation efficiency
of CO emissions than the bus using the aged CCRT. The diesel bus using the fresh
DOC/CCRT had a higher rate of NO emissions reductions and NO2 emissions
increments than the bus using the aged DOC/CCRT, but it did not basically affect
the NOx emissions.
PMID- 29964871
TI - [Studies of Dynamic Adsorption Behavior of VOCs on Biochar Modified by
Ultraviolet Irradiation].
AB - Coconut shell based biochar was modified by ultraviolet irradiation with UV light
at a wavelength of 365 nm in order to enhance the adsorption capacity for
volatile organic compounds (VOCs). The breakthrough curves of biochars for
adsorbing two typical VOCs (benzene and toluene) were examined. The results
showed that the adsorption capacity of modified biochar was greatly increased.
The saturation adsorption capacity of modified biochar for benzene and toluene
was increased to 122.80 mg.g-1 and 236.36 mg.g-1, comparing
to that of the pristine biochar (7.27 mg.g-1 and 7.98 mg.g
1, respectively). The breakthrough time of modified biochar for benzene and
toluene (390 min and 620 min) was also drastically prolonged as compared to the
raw biochar (1 min and 2 min). The characterization analysis of biochars
suggested that the carboxylic groups and external surface area were largely
enriched, which might be the main factor responsible for the enhanced adsorption
of the two VOCs on the modified biochar. The processes of adsorbing benzene and
toluene at different concentrations on modified biochar were fitted by Yoon
Nelson, Thomas and BDST models. The result demonstrated that these three models
could provide good fitting and the correlation coefficients were all above 0.992.
The TG-DTG result proved that ultraviolet irradiation had little effect on the
thermal stability of biochar. The modified biochar after adsorption saturation
could be reused after thermal regeneration and the regenerated char also had high
adsorption capacity after five times of repeated utilization.
PMID- 29964872
TI - [Absorption Spectral Characteristic Dynamics of Dissolved Organic Matter (DOM)
from a Typical Reservoir Lake in Inland of Three Gorges Reservoir Areas:
Implications for Hg Species in Waters].
AB - Dissolved organic matter (DOM) is an important component in lake eco-systems. It
plays a crucial role in the environmental fate of pollutants such as mercury(Hg),
because of its specific characteristics and functional structures. In this study,
a typical reservoir lake from inland of Three Gorges Reservoir areas, Changshou
Lake was selected to track the changes of DOM geochemical properties for one year
by using UV-Vis absorption spectroscopy technique. Meanwhile, based on observed
Hg data in Changshou Lake, it further validated the key environmental
implications of DOM for Hg distributions in lake. The results showed that as
compared to January, other months including April, June and September had
significantly higher CDOM, but also higher DOC with a slightly decreasing
significance. Dynamics of chromphoric component is an important reason to explain
the seasonal changes of DOM concentration in Changshou Lake. Chromphores of DOM
were mainly derived from high molecular weight (MW) materials with high
aromaticity. Also, three wavelengths fitting model of CDOM could be used for
inversion of DOC concentration in annual monitoring. Meanwhile, seasonal
differences of SUVA254 and S275-295 were significant. Lowest aromaticity
and MW size were observed in January following an obvious increase from April. In
contrast to other types of lakes, DOM aromaticity and MW size in Changshou Lake
were lower than forest lakes, but higher than plateau lakes. Eco-system and land
use types surrounding lakes could have a heavily impact on the heterogeneous
properties of DOM. Importantly, no clear differences between concentrations of Hg
species and SUVA254 and DOC respectively were observed, however chromphoric
component and MW size controlled the dissolved Hg and reactive Hg in lake.
Additionally, enrichment and migration of organic matter resulted from primary
productivity in lake may be a substantial reason to explain the methylmercury
changes.
PMID- 29964873
TI - [Spectral Characteristics of Dissolved Organic Matter (DOM) in Waters of Typical
Agricultural Watershed of Three Gorges Reservoir Areas].
AB - As a key geochemical factor in earth system, dissolved organic matter (DOM) plays
an important role in controlling environmental quality of watersheds. In this
study, a typical agricultural watershed of Three Gorges reservoir areas,
Wangjiagou watershed in Fuling district of Chongqing, was selected to
characterize DOM in waters through fluorescence and UV-Vis spectroscopy, while
the effect of land-use types in this watershed was discussed. The results showed
large spatial variances of aquatic DOM in this watershed, with significant
differences in compositions and sources. After calculation of
ag*(355) for indicating proportion of chromophoric DOM in bulk
DOM, the order of DOM was paddy rice field> ditch> pond> well> outlet point. DOM
samples from paddy rice field and ditch showed higher SUVA254 suggesting higher
aromaticity. DOM from this watershed showed 2 typical types (4 peaks A, C, B and
T) of fluorescent components including humic-like and protein-like components.
Dual contributions from autochthonous (e.g., microbial or alga production) and
allochthonous both heavily affected the DOM characteristics. Besides active
microbial activities due to high organic and nutrients inputs from agricultures,
discharge of sewage and water used in agricultural production could contribute
proteins possibly inducing ascending proportion of protein-like component as
shown in fluorescence analysis. DOM samples from the same sampling points but in
different crop plantation seasons were collected to compare, for understanding
the differences between two planting seasons. It clearly suggested protein-like
component was the key variable to control the DOM dynamics. After land-use
changing from rice/corn into mustard plantation, all of DOC, CDOM and
r(T/C)showed significant differences, but no such observations were
observed in FI, BIX and r(A/C).
PMID- 29964874
TI - [High-resolution Variations of Oxygen and Hydrogen Isotopes of Precipitation and
Feedback from Cave Water: An Example of Jiguan Cave, Henan].
AB - The stable isotopes of atmospheric precipitation that affect the isotopes of
speleothem and cave water are controlled by a variety of factors, such as
temperature, rainfall amount, altitude, vapor source and others. Knowledge in the
factors causing rainfall stable isotopes change is one of the keys to
understanding the cave water stable isotopes change of monsoon-sensitive area in
the north-south China intersection. The samples collected from 4 ground water
sites in Jiguan Cave and the instantaneous heavy rain during Aug.4th
6th, 2015 were analyzed, and combined with the precipitation oxygen
and hydrogen isotopes data for samples from almost 6 years (2009-2015) collected
in Jiguan Cave of Luanchuan County in Henan Province, leading to the following
findings:1 The precipitation was divided into 2 stages with different vapor
sources (high-altitude water vapor from the South China Sea and inland areas from
near the ground to evaporate moisture) that could be recorded in the
delta18O of single rainfall by HYSPLIT model. 2 The evaporation of
stage 2 masked the temperature effect to some extent, which also decreased the
slope and intercept of LMWL and d-excess of precipitation. 3 The
delta18O values feature of cave drip water in Jiguan Cave during this
rainfall was mainly a response to the summer monsoon precipitation from sea
source vapor. The cave drip water of Jiguan Cave responded to the heavy rain very
quickly, and the time was ~3 h. The delta18O of drip became heavier
when dripping rate increased and then decreased slowly. The same pattern could be
found in underground river with slight delay, and the pool near the cave entrance
reflected the difference of precipitation delta18O in two stages.
PMID- 29964875
TI - [Spatial Response of River Water Quality to Watershed Land Use Type and Pattern
Under Different Rainfall Intensities].
AB - Qixiang River watershed, as a typical case study area, was divided into five
types of buffer zones according to elevation and slope. Based on the remote
sensing images, DEM and real-time monitoring data in April, May, June 2015, the
relationship between land use type and pattern in all buffer zones and water
quality under different rainfall intensities was explored. The results showed
that land use type and pattern in different buffer zones had obvious
discrepancies. The proportion of construction land was the highest in low flat
area, secondary flat area and high flat area. The main land use type of
moderately steep area and high steep area was forest land. Secondly, the low flat
area appeared to have the greatest influence on the water quality. Thirdly,
construction land had a greater influence on water quality than other land use
types in low flat area. In addition, in secondary flat area, wetland was the key
factor under small rainfall intensity. However, construction land was the key
factor under moderate rainfall intensity and large rainfall intensity. In
moderately steep area and high buffer zones, construction land influenced the
water quality most under small rainfall intensity but forest land was the
greatest factor under moderate rainfall intensity and large rainfall intensity.
Fourthly, the relationship between the land use pattern and water quality was
complicated. SH-MN had the greatest influence on water quality and the influence
increased with increasing rainfall intensity in low flat area. Furthermore, PD,
SH-MN and SHDI were the key factors in secondary flat area while SH-MN, SHDI and
PD were the key factors in high flat area under all the three types of rainfall
intensity. SH-MN and CONTAG influenced the water quality most in moderately steep
area and high steep area under small and high rainfall intensity. CONTAG
influenced the water quality most in moderately steep area and SHDI was the key
factor in high steep area under moderate rainfall intensity.
PMID- 29964876
TI - [Determination of Background Value and Potential Ecological Risk Assessment of
Heavy Metals in Sediments of the Danjiangkou Reservoir].
AB - The aim of this study was to explore the pollution level and potential ecological
risk of heavy metals in sediments of the Danjiangkou Reservoir, and the study
obtained the background value of heavy metals of the surface sediments using
reference element and statistical methods. The results indicated that the
background values of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb were 41.18, 34, 32.13,
76.84, 10.46, 0.70, 0.07 and 27.11 mg.kg-1, respectively. In addition,
the potential ecological risks of the eight heavy metals in sediments were
assessed using the Hakanson ecological risk index method. The values of RI for
these eight metals in surface sediments ranged from 29.49 to 214.11, with the
mean value of 118.91, and the pollution level was low. Furthermore, the
Cfi value was in the order of Cd> Hg> Zn> Cr> Pb> Ni> As=Cu
with the mean value of 1.05-1.31, and the pollution level varied from low to
intermediate. The Cfi values of Cd and Hg were higher than
those of other heavy metals with the mean values of 1.31 and 1.24, respectively,
which should be paid more attentions.
PMID- 29964877
TI - [Spatial Distribution Characteristics and Risk Assessment of Polychlorinated
Biphenyls (PCBs) in Sediments and Soils from the Dishui Lake and Its River
System].
AB - In order to investigate the pollution levels of PCBs in urban artificial lake,
fourteen PCB congeners in sediments and soils of Dishui Lake and its river system
were quantified by GC/MS, and then the distributions, sources and ecological risk
of PCBs were discussed. The results showed that the concentrations of ?14 PCBs in
sediments and soils ranged from 0.65-16.41 ng.g-1 (dry weight, dw) and
0.47-1.27 ng.g-1, respectively, which were at a low level in general.
Higher concentrations of PCBs were found in surface sediments from the river
system of Dishui Lake than those in surface and core sediments from Dishui Lake,
which indicated that the sediments in Dishui Lake would be polluted by the river
system in the process of diversion. The concentrations of PCBs in core sediments
decreased with depth, which showed that the sediments of Dishui Lake had been
polluted by PCBs since its completion. In all samples, Tetra-CBs and Penta-CBs
accounted for 20.65% and 67.12% of ?14 PCBs, respectively, and PCB105, PCB118 and
PCB77 were the dominant compounds. The results of source apportionment by
principal component analysis (PCA) indicated that PCBs in sediments and soils
from Dishui Lake and its river system were influenced by the historical
cumulative emissions of 2#, 1# PCBs used in China and municipal solid waste
incineration and combustion sources. The toxic equivalents (TEQs) of 12 (DL-PCBs)
ranged from 0.01-79.40 pg.g-1, and the TEQs in 7 samples of surface
sediments from Dishui Lake and its river system were beyond the interim sediments
quality guidelines (ISQGs) suggested by USEPA, which would result in potential
eco-toxicological risks for aquatic organisms.
PMID- 29964878
TI - [Pollution Characteristics and Ecological Risk Assessment of Organochlorine
Pesticides in Water Source Areas of Guangdong and Guangxi].
AB - The concentrations of 16 organochlorine pesticides (OCPs) in 7 water samples
collected from different sites of water source areas of Guangdong and Guangxi
were detected by SPE-GC-MS, and then the pollution characteristics were analyzed.
This study established species sensitivity distribution(SSD) curves with BurrIII
distribution model. In the meantime, HC5 values were calculated by BurrliOZ
software, which were used to evaluate the toxicity effects of OCPs towards
aquatic organisms. Finally, margin of safety concentration values were calculated
to assess the ecological risk. The results showed that the concentration of OCPs
varied from 6.64 to 34.19 ng.L-1, with a mean value of 16.76 ng.L
1, while HCHs and DDTs contributed a lot. HCHs were predominately
originated from lindane, which is a component in household insecticide, while
DDTs were from dicofol contamination or historical residues. Vertebrates could
stand severer toxicity in comparison with invertebrates. alpha-endosulfan
showed a greater toxicity towards aquatic plants and microorganisms than others,
while p, p'-DDT turned out to be the most hazardous pollutant to
vertebrates and invertebrates among the 16 OCPs studied. Generally speaking, OCPs
in study areas didn't show conspicuous ecological risks towards aquatic
organisms, DDTs and alpha-endosulfan, however, are still worth paying
close attention due to their high potential risks.
PMID- 29964879
TI - [Responses of Nutrients and Chlorophyll a to Water Level Fluctuations in Poyang
Lake].
AB - As one of the few remaining lakes that are freely connected with the Yangtze
River, Poyang Lake exhibits a unique aquatic ecology which is different from the
disconnected lakes. In order to study the mechanism of limnological responses to
water level fluctuations (WLFs), samples were collected weekly over 10 months
from September 2011 to December 2012 in Xingzi and Duchang, and the effect of
fluctuations in water level on nutrients and phytoplankton chlorophyll a (Chla)
concentrations was investigated in Poyang Lake. Chla concentrations were strongly
related to WLFs, with higher Chla concentrations in the higher water phase. The
regression analysis indicated that Chla concentrations were significantly and
positively correlated with water temperature (P<0.0001) and secchi depth
(SD) (P<0.0001) but negatively correlated with total and inorganic
nitrogen concentrations (TN,P<0.01; NOx-N,P<0.01;
NH4+-N:P<0.05). SD and total and inorganic nitrogen
concentrations were all significantly correlated with WLFs of Poyang Lake
(SD,P<0.01; TN,P<0.0001; NOx-N:P<0.01;
NH4+-N,P<0.0001). Two different water levels were identified in
the lake by principal components analysis:the low water level with high nutrient
values and the high water level with high water temperature, SD, and Chla values.
These results supported the hypothesis that WLFs clearly exerted an overall
impact on the growth of phytoplankton in Poyang Lake of the Yangtze River
floodplain. WLFs affected the water transparency (expressed by SD), nutrients,
and Chla concentrations of Poyang Lake, likely due to flush flood pulse, re
suspension of suspended matter, dilution effects, and human activities.
PMID- 29964880
TI - [Influence of Periodic Temperature Disturbance on the Succession of Algal
Community Structure].
AB - In order to study the mechanism of the habitat disturbance of reservoir on algae
blooms, some interior control experiments about the feature of algal diversity
and the succession of community structure under different temperature disturbance
cycle but the same amplitude condition were conducted, based on the intermediate
disturbance hypothesis and combined with algal community habitat selection theory
and ecological functional groups of algae. The results showed that:1 the
intermediate disturbance would accelerate the growth of algae and increase their
diversity. Under the gradient of the intermediate disturbance group Delta22C/48h,
the diversity of phytoplankton was the highest, and the biomass reached the
maximum, however, without absolute dominant algal species. While in the high
frequency disturbance group Delta22C/24h the biodiversity was relatively lower,
but the algae biomass was reduced. 2 the periodical change of temperature had
obvious influence on the succession of the phytoplankton community, and the
dominant species also presented certain differences. The succession of the algal
advantageous function group followed the basic rule of X1(Chlorella)
>J(Scenedesmus)->S1(Phormidium) or X2 (Chlamydomonas), and
the community structure also presented a trend that the C/CR type algae took
advantage and the superiority was gradually replaced by R type algae. When the
high temperature disturbance was frequent, the R type algae (S1) was distinctly
ascendant. During the experiment, the community structure was given priority to
the C/R strategy algae with no or low disturbance. However, the coexistence of
algae with different growth strategies was evident in group Delta22C/48h.
Meanwhile, the S strategy algae (L0) resistant to high temperature stress began
to emerge.
PMID- 29964881
TI - [Effects of Bromate on the Growth and Physiological Characteristics of
Chlorella vulgaris].
AB - The effects of bromate on the growth and physiological characteristics of
Chlorella vulgaris were investigated via the static exposure experiments
and tested by flow cytometry. The results showed that when Chlorella
vulgaris was continuously exposed to bromate for 96 h at 8 mmol.L
1, the specific growth rates and cell membrane integrity decreased
significantly, while the esterase activity, mitochondrial membrane potential and
reactive oxygen species (ROS) increased significantly. The membrane-damaged cells
could be found from the scanning electron microscopy analysis. It could be
identified that ROS were overproduced in presence of bromate, which could not be
eliminated by Chlorella vulgaris in time through self-regulation. The
excess ROS could lead to abnormal situation of cell membrane integrity, esterase
activity and mitochondrial membrane potential, disorder of physiology function
and damage of cell structure. It could be concluded that Chlorella
vulgaris died or their growth was inhibited by the existence of bromate.
PMID- 29964882
TI - [Effect of Water Bloom on the Nitrogen Transformation and the Relevant Bacteria].
AB - The biogeochemical cycle of nitrogen in the aquatic environment is the research
hotspot in the world all the time. Nitrification and denitrification are the
special processes of the microorganisms, and also the key steps in the nitrogen
biogeochemical cycle possessing great significance in the freshwater ecosystem.
In the processes of outbreaks of cyanobacterial blooms, total nitrogen,
chlorophyll a, dissolved oxygen and pH decreased sharply, whilst dissolved
organic carbon and ammonium nitrogen increased. The results of simulation of
outbreaks of cyanobacterial blooms using micro-universe system in lab showed that
the amoA gene abundance was reduced in the early stage and AOA was
replaced by AOB gradually. Our results also showed that the amount of
denitrifiers with nirS/nirK was elevated by also 100 times during the
bloom outbreak, which can explain the promoted denitrification in the water
during cyanobacterial bloom.
PMID- 29964883
TI - [Effect of Carbon and Nitrogen Forms on Decomposition of Organic Matter in
Sediments from Urban Polluted River].
AB - To reveal the controlling mechanism of urban polluted river,four trophic level
urban river was studied. The change of distribution of organic matter and
nitrogen in the sediment was studied while the organic matter was disposed. High
level of organic matter is the significant feature of urban city rivers. the
humin (HM) was the major fraction of humus, accounting for more than 65% of OM.
The most proportion of the total nitrogen (TN) was organic nitrogen which
accounted for more than 50%. The amount of organic matter removal increased after
the sediment adsorbed the saturated ammonia, which suggested ammonia as the main
limited factor for the decomposition of organic matter. The most of Ammonia was
adsorbed onto unstable humins. The HM was more stable than other organic matter
which was disposed by Hydrogen peroxide (H2O2).
PMID- 29964884
TI - [Interfacial Property of Amphiphilic Copolymer Blending PVDF UF Membrane and
Protein Anti-fouling].
AB - The phase transformation kinetic process of amphiphilic copolymer
polyoxyethylene/polyoxypropylene/polyoxyethylene[PEO-PPO-PEO(F127)] blending
polyvinylidene fluoride (PVDF) casting solution in an aqueous gel bath was
investigated. The influences of F127 content on the PEO enrichment rate of PVDF
membrane surface, membrane morphology and structural parameters were investigated
by a total reflection fourier transform infrared spectroscopy (ATR-FTIR),
scanning electron microscope (SEM), atomic force microscopy (AFM) and other
analytical techniques. F127/PVDF blending membrane fouling behavior of bovine
serum albumin (BSA) was evaluated by the static adsorption capacity, normalized
filtration decay rate and membrane fouling resistance model. The results showed
that the membrane delayed phase separation process increased, the membrane
surface, internal pore size and porosity increased and the surface roughness
increased with increasing F127 addition, and the increment of PEO enrichment rate
on the membrane surface became stable when the F127 content reached 15%. F127
blending membranes with F127 contents ranging from 15% to 25% had a higher flux
and BSA rejection, lower static adsorption capacity, slower flux decay rate,
lower irreversible fouling index and smaller pore blocking resistance and cake
layer resistance distribution coefficient, which showed a good anti-fouling
property.
PMID- 29964885
TI - [Adsorption of Hg(II) in Water by Sulfydryl-Modified Sepiolite].
AB - In order to develop highly efficient and low-cost treatment technique for heavy
metal wastewater and promote the resource utilization of sepiolite, natural
sepiolite was modified by using thioglycollic acid and characterized by scanning
electron microscope (SEM), X-ray diffraction (XRD), specific surface, Zeta
potential and infrared spectrum (IR) analysis, and the adsorption kinetic and
thermodynamic characteristics of the modified sepiolite to Hg(II) in water were
studied by static adsorption experiments. The results showed that sulfydryl
groups were grafted onto sepiolite, and the surface of the modified sepiolite
became smoother with more gaps and negative charges to improve the adsorption
ability for Hg(II). The optimal pH for Hg(II) adsorption on the modified
sepiolite was 6, and the adsorption process reached equilibrium in 60 min at 30C.
This process could be described by the pseudo second-order kinetic equation, and
the initial adsorption rate constant was 0.063 mg.(g.min)-1. The
adsorption thermodynamic characteristics could be well described by Langmuir
isothermal adsorption model, and the maximum adsorption capacity was 3.256
mg.g-1. The investigation revealed that the adsorption process was a
spontaneous endothermic process, resulting in physical adsorption and chemical
adsorption, which was dominated by physical adsorption.
PMID- 29964887
TI - [Adsorption Characteristics of 2,4-D on UiO-66 from Wastewater].
AB - With UiO-66 metal organic framework as the adsorbent, the influences of factors
such as time, pH value, temperature on the adsorption were studied. The results
showed that the adsorption effect was best at pH=4.0 for the adsorption system
and the adsorption equilibrium time was 24 h. The equilibrium adsorption capacity
increased with the increasing temperature and the optimal temperature should be
controlled at 30C. The adsorption of 2,4-D on UiO-66 followed Langmuir isotherm
model and the adsorption kinetics could be better described by pseudo-second
order model. The intraparticle diffusion process was the rate-controlling step
for adsorption processes. The results of thermodynamic calculations showed that
DeltaG<0, DeltaH>0, DeltaS>0. So the adsorption was a
spontaneous, endothermic chemical process with increased randomness. The main
interaction forces of adsorption were chemical bonding force and electrostatic
interactions force. Results of the study suggested that UiO-66 had the potential
ability for 2,4-D removal from wastewater.
PMID- 29964886
TI - [Adsorption Behavior of Low Concentration Phosphorus from Water onto Modified
Reed Biochar].
AB - In order to remove low concentration of phosphorus in wastewater and realize
resource utilization of reed, reed biochar(RB) was prepared using reed and then
modified by ferric chloride, and the adsorption behavior of low concentration
phosphorus was investigated. The results showed that the iron content of modified
reed biochar(MRB) was 11.98 mg.g-1, which was 44.7 times that of RB;
pHpzc of the MRB was 7.49, and the adsorption effect was the best when the
solution pH was 7.0; at the initial concentration of 4.0 mg.L-1 and
temperature of 298K, the adsorption capacity of MRB was 0.658 mg.g-1,
which was 34.6 times that of RB. The adsorption isotherms at different
temperatures were well fitted to Langmiur equation, which indicated the
adsorption was monolayer adsorption, and increasing temperature was favorable for
adsorption. DeltaGtheta<0, DeltaHtheta>0 and
DeltaStheta>0 indicated that the adsorption was a spontaneous,
entropy increasing and endothermic process. The kinetic experimental data of the
adsorption fitted well to the pseudo-second-order equation, the initial
adsorption rate increased with the increasing initial concentration of solution,
and the adsorption was mainly controlled by intraparticle diffusion. The research
will provide basic data for application of MRB in deep removal of low
concentration phosphorus from sewage treatment plant and water body.
PMID- 29964888
TI - [Mechanism and Surface Fractal Characteristics for the Adsorption of p
nitrophenol on Water-quenched Blast Furnace Slag].
AB - In the present study, the removal of p-nitrophenol (p-NP) from
aqueous solution through the adsorption on water-quenched blast furnace slag
(WBFS) was investigated. The physicochemical properties of the slag were
characterized by SEM, XRD, FTIR and BET. Batch experiments were conducted to
investigate the mechanism, kinetics and thermodynamics of adsorption process. The
results showed that the experimental data could fit to Freundlich model. The
enthalpy change (DeltaH) and entropy change (DeltaS) were 3.29
kJ.mol-1 and 4.66 J.(mol.K)-1, respectively. It indicated
that the adsorption of p-NP on WBFS was an endothermic and entropy
increasing process. The values of DeltaG decreased with increasing
temperature, indicating the spontaneous adsorption proportional to the
temperature. The adsorption could be divided into two parts, one was high-speed
surface coverage, and the other was slow-speed internal diffusion adsorption. It
was also found that the adsorption process followed the pseudo-second-order
kinetic model. The fractal dimensions of WBFS surface calculated by Freundlich
adsorption fractal model were 2.78, 2.80, 2.84 and 2.87 at different
temperatures, respectively. It indicated the existence of fractal phenomenon with
higher fractal dimension of WBFS at higher temperature.
PMID- 29964889
TI - [Adsorption Characteristics for Humic Acid by Binary Systems Containing Kaolinite
and Goethite].
AB - In this study, the binary systems of kaolinite-goethite mixture (KGM) and
kaolinite-goethite complex (KGC) were prepared by different methods, and the
surface properties and humic acid adsorption of the samples were investigated.
Results showed that the specific surface area (SSA) of the samples followed the
order of goethite> KGC> KGM> kaolinite, and the SSAs increased significantly for
KGC while slightly for KGM when compared to the average value of kaolinite and
goethite. The isoelectric point (IEP) of kaolinite, goethite, KGM and KGC
appeared around 3.2, 7.9, 6.1 and 6.7, and the Zeta potential at pH 5.0 was
13.9, 38.2, 14.3 and 19.7 mV, respectively. The adsorption kinetic data for humic
acid were well fitted using the pseudo-second-order kinetic models, suggesting
that chemisorption was important in the adsorption process. Both one-site and two
site Langmuir models were suitable to describe the isotherm adsorption data
(R2 0.962-0.993), and the correlation coefficients of two-site
model for the binary systems were relatively higher (R2>0.989).
The R2 values of Freundlich model fiting the adsorption data
were low for the four samples, especially for the two pure samples. This
indicated that the adsorption with various sites and mono-layer model was
important in adsorbing humic acid onto the binary systems. At the initial pH of
5.0, the adsorption capacity (qmax) of kaolinite, goethite, KGM and KGC
was 6.02, 61.83, 35.13 and 42.10 mg.g-1, respectively. The qmax
values of KGC and KGM increased to different extents when compared to the average
of kaolinite and goethite. Thermodynamic parameters indicated that the adsorption
of humic acid were endothermic for the four samples and non-spontaneous for
kaolinite while spontaneous for the other samples.
PMID- 29964890
TI - [Effects of Sulfur/sponge Iron Ratio for Deep Denitrification and Phosphorus
Removal of Reclaimed Water].
AB - To study the effects of sulfur/sponge iron ratio on denitrification and
phosphorus removal, a series of static experiments were conducted using different
ratios of sulfur and sponge iron. The results showed that the denitrification and
phosphorus removal effect of sulfur/sponge iron composite fillers was
significantly higher than that of single filler, and sulfur/sponge iron ratio was
one of the key factors influencing nitrogen and phosphorus removal by composite
fillers. When the volume ratio was equal to or greater than 1:1, the removal
efficiency of TN and TP reached 85% and 97%, respectively. The denitrification
and phosphorus removal process of the composite fillers both fitted second-order
kinetic equation, the denitrification was dependent on heterotrophic
denitrification and sulfur autotrophic denitrification; the phosphorus removal
was mainly chemical phosphorus removal caused by sponge iron corrosion.
PMID- 29964891
TI - [Effect of Element Sulfur Particle Size and Type of the Reactor on Start-up of
Sulfur-based Autotrophic Denitrification Reactor].
AB - The effect of element sulfur particle size and type of the reactor on sulfur
autotrophic denitrification reactor start-up was researched at room
temperature(19-24C) by using sulfur autotrophic denitrification bio-membrane
reactor and anaerobic sludge bed biofilm reactor and inoculating anaerobic
sludge. The research indicated that after 65 d operation, the bio-membrane
reactor gained steady denitrification efficiency. With an influent NO3
-N of 150 mg.L-1, and an HRT of 3.3 h, the removal efficiencies
of NO3--N and TN were 91% and 77%, and the removal rate of TN was 0.67
0.83 kg.(m3.d)-1. The increase of volumetric loading rate
of NO3--N and production of nitrogen gas led to the floating of sludge
in the anaerobic sludge bed biofilm reactor. With an influent NO3--N
of 185 mg.L-1 and an HRT of 3.3 h, the maximum removal rate of
NO3--N of 1.1 kg.(m3.d)-1 was attained in
anaerobic sludge bed biofilm reactor. But the increase of effluent NO3
-N and NO2--N lowered the quality of effluent water seriously,
and the floating of sludge affected the steady operation of the anaerobic sludge
bed biofilm reactor. Sulfur particles with particle size of 0.8 mm and 3.0 mm
were used as electron donors for start-up of two batch reactors. The experiment
results indicated that the reactor which used sulfur particle size of 0.8 mm
attained higher removal efficiency of NO3--N and TN, and its effluent
accumulated less NO2--N compared with the reactor which used particle
size of 3.0 mm.
PMID- 29964892
TI - [Influencing Mechanism of Titanium Salt Coagulant Chemical Conditioning on the
Physical and Chemical Properties of Activated Sludge Flocs].
AB - The effect of the different forms of titanium salt coagulant conditioning on
sludge dewatering performance was studied. The result showed that the sludge
dewaterability was the best and the specific resistance to filtration (SRF), the
compressibility and the content of organic content in EPS were the lowest when
B=0.5 compared with others. The optimal dosage of polymeric titanium
chloride (PTC) was 0.005 g.g-1, which was far less than those of the
traditional iron salts and aluminum coagulants. When the dosage of PTC with
different B values was 0.005 g.g-1, the order of dewaterability
was:PTC 0.5> PTC1.5> TiCl4> PTC2.5. In addition, the variations of
characteristics such as particle size (d0.5) and fractal
dimension(DF) of sludge during conditioning were analyzed. The effect of
titanium salt coagulant conditioning on the distribution and composition of the
sludge extracellular polymeric substance(EPS) was characterized by Three
dimensional Excitation Emission Matrix Fluorescence (3DEEM) and High Performance
Size Exclusion Chromatography(HPSEC).The decrease of fluorescent intensity and
molecular weight of peak distribution and intensity of organics in EPS was highly
correlated to the improvement of the dewatering performance and change of sludge
properties.
PMID- 29964893
TI - [Distribution Characteristics of Methanogens in Urban Sewer System].
AB - A study was conducted through a 1200 m-PVC-pipe-reactor, which was used to
simulate the urban sewer system. Gas chromatography, liquid chromatography and
454 high-throughput sequencing were utilized to study the variation of substrates
during the methanogenic process and the distribution characteristics of
methanogens in the sewer system. The results showed that the concentration of
methane increased along the sewer system, which illustrated that methanogens
existed in the sewer network. The methanogens mainly contained Methanosarcina,
Euryarchaeota_unclassified and Methanobacteriaceae_unclassified. The
distinct succession which Euryarchaeota_unclassified replaced
Methanosarcina to be the first dominant microbial genus between 800-1000 m
of the sewer system. Formic acid, methanol, methylamine, acetic acid and hydrogen
were available substrates for methanogens. Among these substrates, acetic acid
was the primary substrate for methanogen. The variation trends of these
substrates were first increasing and then decreasing along the length of the
sewer system, which led to the succession phenomenon of methanogens in the sewer
system.
PMID- 29964894
TI - [Long-term Performance and Bacterial Community Composition Analysis of AGS-SBR
Treating the Low COD/N Sewage at Low DO Concentration Condition].
AB - This study utilized the sequencing batch activated sludge reactor (SBR)
inoculated aerobic granular sludge (AGS) to treat the low COD/N ratio (<4.0)
domestic wastewater under low DO (0.5-1.0 mg.L-1) concentration
condition. Long-term performance of simultaneous nitrogen and phosphorus removal
and bacterial community composition of AGS-SBR were studied. The results showed
that the AGS-SBR system had good and stable decontamination abilities in its 180
day operation. The average removal rates of COD, NH4+-N, TN and TP
were 87.17%, 95.21%, 77.05%, and 91.11%, respectively. At the same time, the AGS
showed good settling performance, and always kept its integrated and compact
structure. No obvious granular sludge disintegration phenomenon occurred in 180
days. Meanwhile, by using Illumina 16S rRNA gene MiSeq sequencing, we
investigated the bacterial abundance in AGS-SBR reactor. Proteobacteria,
Firmicutes, Chlorobi, Chloroflex, and Bacteroidetes were the dominant microbial
communities in the simultaneous nitrogen and phosphorus removal reactor.
Denitratisoma, Planctomycetaceae, Thauera, Comamonas,
Nitrosomonas and Nitrospira were suggested to be the primary
organisms responsible for the nitrogen removal. Clostridium and
Anaerolinea were the main bacterial communities of phosphorus removal.
PMID- 29964895
TI - [Optimization for Microthrix parvicella Quantitative Processing of
Fluorescence in situ Hybridization (FISH)].
AB - Precise quantification of Microthrix parvicella, which is identified as a
dominated filamentous bacterium of bulking sludge in the worldwide, is essential
for bulking investigation and related control strategies. However, quantitative
processing based on fluorescence in situ hybridization (FISH) is prone to
interference due to the specific characteristics of Microthrix parvicella
(hydrophobic surface with thick cell wall). Our study focused on pretreatment and
process optimization to show that the proportion of Microthrix parvicella
was increased from 1.12% to 96.70% benefited by lysozyme (36000 U.mL
1), high probe concentration (4.5 ng.MUL-1) and longer
hybridization time (4 h) employed, mapping with the results of q-PCR method and
Eikelboom & Jenkins Observation.
PMID- 29964896
TI - [Influence of Carbonization Temperature on Bacterial Community of the Biological
Carbon Electrode Based on High-throughput Sequencing Technology].
AB - Microbial diversity of anodic biofilm in bioelectrochemical systems with hemp rod
carbonized at 1000 and 1800C as anode was investigated using Solexa high
throughput sequencing technology. The results showed that a total of 4231 and
5263 optimized 16S rRNA gene sequences were gained from the electrode biofilm on
the hemp rod carbonized at 1000 and 1800C, respectively. At the level of 97%
similarity, 1187 and 1338 OTUs were obtained for electrode biofilm carbonized at
1000 and 1800C, respectively. The result of alpha diversity analysis showed that
microbial diversity increased with decreasing carbonization temperature. Dominant
phylum for both biofilms were Proteobacteria, Firmicutes and Bacteroidetes, which
accounted for 66%, 10% and 9%, respectively for 1000C, while 71%, 7% and 9%,
respectively for 1800C. Beside the coexisting phylum, some unique species were
also discovered, demonstrating that carbonization temperature did not only
influence the electrode structure, but also affected the microbial community
structure.
PMID- 29964897
TI - [Isolation, Identification and Characteristics of a Rhodopseudomonas with
High Ammonia-nitrogen Removal Efficiency].
AB - A strain of photosynthetic bacterium named psb1 capable of ammonia-nitrogen
degradation was isolated from a swamp in Yunnan. The psb1 was similar to
Rhodopseudomonas sp. according to its cell morphological properties and
absorption spectrum analysis of living cells. The alignment result of 16S rDNA
amplification sequence with specific primers of photosynthetic bacteria showed
that the homology between strain psb1 and Rhodopseudomonas sp. was 99%,
and the alignment results of protein sequences of bacterial chlorophyll Y subunit
showed that the strain psb1 and Rhodopseudomonas palustris were the most
similar, with a similarity of 99%. But there was a great difference in the
biological properties of the strains psb1 and Rhodopseudomonas palustris
according to physiological biochemical characteristics and main fatty acid
analysis. For example, strain psb1 could not utilize glucose and mannitol as
carbon source, and had specific fatty acid C18:1omega6c. The results of single
factor test showed that:the optimal growth was obtained at pH 7.0 and 40C, the
optimal nitrogen source was yeast extract. The optimal conditions for ammonia
nitrogen biodegradation were as following:anaerobic, light, initial pH 6.0-7.0,
temperature 30C, inoculation volume 0.4%. Under that cultural condition, the
degradation rate of ammonia nitrogen in wastewater could reach 99%. The results
indicated that strain psb1 might be a novel bacterium in genus
Rhodopseudomonas with high ammonia removal efficiency, and can be applied
in the bioremediation of polluted landscape water.
PMID- 29964898
TI - [Variation Characteristics of Inorganic Phosphorus in Purple Soil Profile Under
Different Conservation Tillage Treatments].
AB - In this study the effects of tillage methods (rice-winter paddy field
conventional farming, CF; rice-winter paddy field combing ridge with no-tillage,
RNT1; rice-wheat or rape combing ridge with no-tillage, RNT2; rice-wheat or rape
conventional paddy-upland rotation tillage, CR) on purple soil profile of
different forms of inorganic phosphorus distribution characteristics were
investigated in a long-term experimental site established in 1990, Chongqing
City, China. The results showed that compared to the status before the
experiment, the total phosphorus, available phosphorus and various morphologies
of inorganic phosphorus all increased to a certain degree in the soils with
different long-term tillage treatments,and the contents of different forms of
inorganic phosphorus in soil size ranked as RNT2> CF> CR> RNT1. Except that the
contents of Fe-P in the lower layer were higher than those in the upper layer,
contents of Ca2-P, Ca8-P, Al-P, Ca10-P and O-P in the arable layers were all
higher than those in the lower layers. The effects of farming practices on the
availability of various phosphorus forms were significant. They were in the order
of CR> RNT> CF. Long-term conventional paddy-upland rotation tillage was more
advantageous to crops in the absorption of phosphorus. It was shown by relevant
analysis that the contribution of various groups of inorganic phosphorus to
purple soil was in the order of Ca2-P(0.9369)> Al-P(0.9158)> Ca8-P(0.9012)> Fe
P(0.8287)> Ca10-P(0.8059)> O-P(0.7472).
PMID- 29964899
TI - [Effect of Different Organic Materials on Nitrogen Mineralization in Two Purple
Soils].
AB - An aerobic incubation experiment was conducted at a constant temperature to
investigate the differences in nitrogen mineralization between an acid purple
soil and a calcareous purple soil amended with five organic materials including
biogas residues of pig manure(PM), cow manure(CW), sewage sludge compost(SC),
rural waste compost(RWC1)and the compost of rural waste plus 20% of sewage
sludge(RWC2). The results showed that the organic nitrogen forms in these
materials followed the order of amino acid N> hydrolysable unidentified N>
ammonium N> non-hydrolysable N> amino sugar N. Application of organic materials
could significantly improve the contents of NH4+-N and NO3-
N in acid purple soil, PM and SC could significantly improve the content of
NH4+-N, but CM reduced the content of NO3--N in calcareous
purple soil. Except for CM, which had no significant effect on the quantity of
nitrogen mineralization in acid purple soil, but decreased the quantity of
nitrogen mineralization in calcareous purple soil, applying the organic materials
could significantly increase the quantity of nitrogen mineralization in both
soils. Correlation analysis showed that the quantity of nitrogen mineralization
was significantly and positively correlated with the contents of amino acid N and
ammonium N, but were significantly and negatively correlated with the content of
organic matter and the C/N of organic materials. Overall, the results illustrated
that the effect of organic materials on the mineralization of nitrogen varied
with soil types and the characteristics of organic materials, especially the
content of organic matter, C/N and the fractions of organic nitrogen in organic
materials.
PMID- 29964900
TI - [Impacts of Biochar and Straw Application on Soil Organic Carbon Transformation].
AB - To explore the effects of biochar and straw application on soil carbon
constitution and transformation, an incubation experiment was conducted to study
the characteristics of the release of carbon dioxide,as well as the changes in
microbial biomass carbon and organic carbon in soil after applying biochar or
straw only, or biochar plus straw. The results showed that the straw
mineralization rate of organic carbon in soil was 21.50% at 2% application level,
which was much higher than that of biochar (8.09%). With the same addition amount
of biochar and straw at 4% level for 200 days incubation, the soil organic carbon
content was 24.40 and 17.40 g.kg-1,respectively. It suggested that the
positive impact of biochar application on improving soil organic carbon was
greater than that of straw. The application of biochar had protective function on
soil original organic carbon. Biochar promoted the straw mineralization and
resulted in positive interaction effect between biochar and straw on
mineralization of soil organic carbon. The application of straw increased soil
microbial biomass carbon (MBC) greatly, while biochar had less impact on MBC. The
application of straw and biochar also increased soil microbial biomass carbon,
but the interaction effect could be positive or negative, which was dependent on
the incubation time or application rate.
PMID- 29964901
TI - [Tracing Sources of Heavy Metals in the Soil Profiles of Drylands by Multivariate
Statistical Analysis and Lead Isotope].
AB - Two profile soils in drylands of Xiamen City were collected and 26 kinds of heavy
metals were determined by ICP-MS. The distribution characteristics, environmental
risk and pollution sources of heavy metals in soil profiles were studied. The
results of Nemero comprehensive pollution index method, the geological
accumulation index method and potential ecological hazard index method indicated
that Cd was the main pollution factor in the drylands of Xiamen City; the soil
pollution was serious in 50-60 cm depth. Multivariate statistical analysis showed
that the main sources of heavy metals were the compound pollution of agricultural
production activities and natural resources, and the main pollution factor Cd was
from agricultural production. Composition of acid-extractable Pb isotopic ratios
in soil profiles and potential pollution sources were analyzed. The results
showed that Pb in soil profiles was from sludge and parent material. The
contribution rates of the two sources in the soil profiles by
206Pb/207Pb-206Pb/204Pb were
calculated by using the two mixed models. In the two profiles, parent material
contribution rates were 54.36% and 42.88%, and sludge contribution rates were
45.64% and 57.12%, respectively. The main sources of lead of drylands in Xiamen
were parent material and sludge, which was consistent with the results of the
multivariate statistical analysis.
PMID- 29964902
TI - [Landscape Patterns Characteristics of Soil Heavy Metal Pollution in a Town of
Southern Jiangsu].
AB - It is of great significance to evaluate the soil heavy metal pollution level and
to know their spatial distribution characteristics. Taking soil heavy metals As,
Cd, Cr, Cu, Hg, Ni, Pb and Zn in a town of southern Jiangsu as research objects,
using the single factor evaluation method, Nemerow comprehensive evaluation
method, geostatistical analysis method together with the landscape pattern grain
effect and the landscape index analysis method, we studied their characteristics
of landscape patterns in the study area based on pollution evaluation. The
results showed that:1 The average value range of single factor pollution index
and Nemerow comprehensive evaluation index for soil heavy metals in study area
was 0.145-0.893.The overall pollution level was low. The pollution level of south
area was lower than that of north area; 2 As, Pb, Hg, and Zn elements showed
obvious non-point pollution characteristics.As and Pb showed a similar spatial
distribution. So were Hg and Zn elements. In contrast, Cd, Cr, Cu and Ni elements
showed obvious point pollution characteristics. Cd and Cr showed similar spatial
distribution. So were Cu and Ni elements; 3 The suitable grain effect landscape
index of nine soil heavy metals pollution landscape was 30-40 m; 4 The low
concentration area of soil heavy metals in the study area accounted for the
largest proportion. The border of lower concentration area was the most complex
part. The distribution of all pollution level areas was relatively concentrated
and the comprehensive pollution fragmentation degree was low. The source
pollution of soil heavy metals was in concentrated distribution, and its number
still counted low, but there was a tendency for further development. As a whole,
it was still in the early pollution stage of soil heavy metals.
PMID- 29964903
TI - [Assessment and Pollution Characteristics of Heavy Metals in Soil of Different
Functional Areas in Luoyang].
AB - The residential areas, science and education areas, urban green lands, commercial
districts, urban arterial roads, industrial zones and urban and rural junction
districts in seven different functional zones of Luoyang City were taken as
research subjects, and sixty-three soil samples were gathered. The concentrations
of soil heavy metals were measured and their pollution levels were evaluated by
single pollution index and Nemerow complex pollution indices. The ecological
risks of soil heavy metals were discussed with Hakanson potential ecological risk
index (RI) and their geneses and sources were indicated by the principal
component analysis (PCA). The results showed that the average level of all heavy
metals exceeded the background values of Henan Province. The pollution degree of
single gene index was in the following order:Cd> Zn> Pb> Cu> Ni> Cr. Nemerow
complex pollution indices indicated heavy metals had the highest concentration
and the heaviest pollution in industrial zones. A single heavy metal potential
ecological harm (Eri) showed Cd had the highest risk index. RI
was ranked as industrial zones> urban arterial roads> commercial districts>
residential areas> science and education areas> urban green lands> rural junction
districts. The heavy metal pollution in industrial zones, urban arterial roads
and commercial districts reached strong levels, and the pollution in residential
areas, science and education areas, urban green lands reached moderate risk
levels, but that in rural junction districts belonged to slight risk level. Cu,
Zn, Pb and Cd were called anthropogenic factors and came from industrial wastes
and transport emissions, but Cr and Ni were explained as natural factors and
their contents depended upon the parent materials of soil.
PMID- 29964904
TI - [Evaluation on Heavy Metal Pollution and Its Risk in Soils from Vegetable Bases
of Hangzhou].
AB - With the purpose of investigation on heavy metal contamination in soils from
vegetable bases of Hangzhou, adopting field investigation and indoor analysis
methods, the contents of heavy metals as Cu, Zn, Pb, Cd, Cr, As and Ni, together
with their relevance to the physicochemical properties of the 203 soils from 30
vegetable bases in 10 districts of Hangzhou were studied. The results showed that
the contents of heavy metals such as Zn,Cr,As,Ni generally didn't exceed the
standard, while the contents of heavy metals such as Cu, Pb, Cd exceeded it. The
results from synthetic pollution evaluation showed that the soils were slightly
polluted in soils from vegetable bases of Hangzhou, which were mainly caused by
Cd pollution. Furthermore, there was slight potential ecological hazard for Cu,
Zn, Pb, Cr, As and Ni but strong potential ecological hazard for Cd, and medium
comprehensive ecological hazard as a whole for all the heavy metals in soils from
vegetable bases of Hangzhou. The correlation analysis indicated that the contents
of Cu, Zn, Pb, As, Cd were greatly influenced by the soil physicochemical
property. Thus, measures must be taken for the prevention and controlling of
heavy metal pollution in the soils from vegetable bases in Hangzhou, especially
for that of Cd.
PMID- 29964905
TI - [Fluorescence Spectroscopic Characteristics and Cu2+-complexing
Ability of Soil Dissolved Organic Matter].
AB - Extracted and dialyzed from four kinds of soil and chicken manure, DOM samples
were analyzed to investigate their molecular weight distribution, chemical
structure characteristics and the metal binding capacity. The results showed that
the integral area of the molecular weight of chicken manure DOM was much higher
than those of other samples, which indicated the high content of organic matter.
And the peat soil followed it. The integral areas of dark brown soil, cinnamon
soil and black soil were low, accounting for only 4.5%-5% of chicken manure
integral area. The integral area of chicken manure DOM in middle molecular weight
fraction accounted for about 34.1% of the total material, while those in low
molecular weight and high molecular weight fractions accounted for about 41.7%
and 24.2%, respectively. The protein-like fluorescence peaks
(Ex/Em=240-270/300-350 nm) were present in all samples, and absent
in middle and high molecular fractions (Mr>500) for dark brown soil. The
visible fulvic acid-like florescence peaks (Ex/Em=325/420 nm)
observed in peat soil, and the florescence peaks of black soil in the middle and
high molecular fractions (Mr>500) both had a red shift phenomenon. The DOM
of chicken manure had the UV-fulvic acid-like florescence peaks similar to black
soil, and the visible fulvic acid-like florescence peaks similar to peat soil.
Furthermore, it had a kind of protein-like fluorescence peak
(Ex/Em=280/350 nm) that was absent in the middle molecular weight
fraction (500< Mr< 12000). The Cu2+ complexation constant was
4.13 for peat soil, and smaller for other three kinds of soil (between 2.10 and
3.10). Chicken manure showed the greatest ability to bind Cu2+ with a
resulting complexation constant of 6.66, indicating the importance of the unique
peak, protein-like fluorescence peak, in the chicken manure of the low and high
molecular weight fractions.
PMID- 29964906
TI - [Effect of Stabilizer Addition on Soil Arsenic Speciation and Investigation of
Its Mechanism].
AB - Arsenic toxicity, mobility and bioaccessibility are influenced by its different
speciation in soil, which exerts different impacts on the environment. In this
study, coal fly ash, dried sludge, ferrous sulfate and broken peanut shell were
used as stabilizers to investigate their stabilizing effects on As in soil as
well as relationships between pH, soil organic matter content, cation exchange
capacity and speciation of soil As. The results showed rise in soil pH, soil
organic matter content and residual arsenic content after the addition of
stabilizers. Addition of 10% coal fly ash and 10% dried sludge led to the
decrease in the content of exchangeable As, carbonate bound As, Fe-Mn oxide bound
As, organic bound As by 34.2%, 17.5%, 19.9%, 53.7%, respectively. Addition of
ferrous sulfate could preferably stabilize As in soil. When 10% coal fly ash, 10%
dried sludge and 1% ferrous sulfate were added concurrently, the decrease in the
content of exchangeable As, carbonate bound As, Fe-Mn oxide bound As, organic
bound As was 62.3%, 55.2%, 29.6%, 58.2%, respectively, with an increase in
residual arsenic content by 8.1%. After the addition of 10% coal fly ash, 10%
dried sludge, 1% ferrous sulfate and 1% broken peanut shell, a most conspicuous
decrease in the content of exchangeable As by 73.3% was observed. Appropriate
application of coal fly ash, dry sludge and ferrous sulfate converted a
proportion of exchangeable, carbonate bounded, Fe-Mn bounded, organic bounded As
into residual As, which reduced As's toxicity. The rise in pH led to increasing
residual As content and decreasing exchangeable As, carbonate bounded As, Fe-Mn
bounded As and organic bounded As content, and As was most stable at the approach
of neutral condition. The rise in organic matter content led to increasing
carbonate bounded As and residual As content and decreasing exchangeable As, Fe
Mn bounded As, organic bounded As content. The rise in cation exchange capacity
led to increasing residual As content and decreasing exchangeable As, carbonate
bounded As, Fe-Mn bounded As and organic bounded As content.
PMID- 29964907
TI - [Effects of Human Gut Microbiota on Bioaccessibility of Soil Cd, Cr and Ni Using
SHIME Model].
AB - The influence of human gut micobiota on bioaccessibilities of soil Cd, Cr, and Ni
were investigated in this study. Five soil samples were collected from some sites
of China, and the bioaccessibilities of soil Cd, Cr, and Ni in the gastric, small
intestinal, and colon phases were determined using the PBET method
(physiologically based extraction test) combined with SHIME model (simulator of
human intestinal microbial ecosystem). The results showed that the
bioaccessibilities of Cd, Cr, and Ni in the gastric phase were 4.3%-94.0%, 6.4%
21.6%, and 11.3%-47.3%, respectively. In the small intestinal phase, the
bioaccessibilities of Cr and Ni were either congruent or slightly increased,
while for Cd, the values were reduced by 1.4-1.6 folds except for soil 2. In the
gastric and small intestinal phases, the mean bioaccessibility of Cd was higher
but that of Cr was lower. In the colon phase, the bioaccessibilities of Cr and Ni
were 1.3-2.4 and 1.0-2.1 times higher than those in the small intestinal phase.
Furthermore, the bioaccessibility of Cd also increased except for soil 3 and 4.
Human gut micobiota could induce Cd, Cr, and Ni release from soils and increase
their bioaccessibilities, which may result in high risk to human health.
PMID- 29964908
TI - [Photosynthetic Characteristics and Ozone Dose-response Relationships for
Different Genotypes of Poplar].
AB - The open top chambers were used to explore the photosynthetic characteristics of
three genotypes of poplar ('546', '90' and '84K') in response to different ozone
exposures. The results showed that net photosynthetic rate (Pn),
transpiration rate (Tr), water use efficiency (WUE), apparent electron
transport rate (ETR), excitation energy capture efficiency of PSII reaction
center (F'v/F'm), coefficient of photochemical quenching (qP),
actual photochemical efficiency of PSII in the light (PhiPS2), chlorophyll a
(Chla), chlorophyll b (Chlb), total chlorophyll (Chla+b) and carotenoid
(Car)contents were significantly decreased with the increasing ozone
concentrations. However, intercellular CO2 concentration (ci) was
significantly increased and stomatal conductance (Gs) remained unchanged.
There was significant difference in photosynthetic characteristics among three
genotypes of poplar. The genotype'546' showed a significant linear correlation
(P<0.01) between photosynthetic parameters (except Gs) and the
ozone dose index AOT40(accumulated hourly O3 concentration over a threshold of 40
nmol.mol-1 during daylight hours). Among the three genotypes of
poplar, photosynthesis pigments contents in '546' significantly declined with the
increase of ozone concentration but not in '90' and '84K'. According to the
linear relationship of most photosynthetic parameters and AOT40, especially the
total chlorophyll, '546' showed the maximum slope, follows by '90' and then
'84K'. So the order of the ozone sensitivity of three poplar genotypes was '546'>
'90'> '84K'. The results of this study can provide an important basis for
breeding ozone resistant genotype of poplar as well as protecting poplar from
ozone damage.
PMID- 29964909
TI - [Effects of Pyrene on Low Molecule Weight Organic Compounds in the Root Exudates
of Five Species of Festuca].
AB - Phytoremediation is an important measure to remove organic pollutants from
contaminated soil, and the root secretion of plant is considered to be closely
related to the mechanisms of phytoremediation of organic pollutants. It is in
favor of revealing the mechanisms of remediation by studying the characteristics
of root exudates of plants with phytoremediation potential under the stress of
pollutants. In the present research, pyrene and five species of Festuca
which have been testified to be tolerant to pyrene stress were selected as
studied objects. A soil-cultivating experiment with rhizobag technique was
conducted to investigate the effects of pyrene on low molecule weight organic
compounds in the root exudates of plant species under five concentration levels
of pyrene (10.19, 20.32, 40.36, 79.94,and 160.68 mg.kg-1,denoted by
C1, C2, C3, C4 and C5,respectively) on day 30, 40, 50, 60 and 70 of experiments.
The results showed that the presence of vegetation significantly enhanced the
dissipation of pyrene in the soil environment. This effect was especially marked
with Festuca arundinacea, followed by those with Festuca mazzetiana,
Festuca pubiglumis, and Festuca longiglumis, and that with Festuca
stapfii was the lowest. During the whole experiments, the amounts of soluble
sugar excreted by the five species of Festuca tested in root exudates were
promoted with pyrene stress, then fluctuated with a stable trend along with the
increase of stress concentration or the extension of stress period, which
appeared to rise appreciably at relative low pyrene spiked (C1-C3) or earlier
stress stage (30-40 d) and reduce at relative high pyrene spiked level (C3-C5) or
later stress stage (40-70 d), and the highest amount of soluble sugars in root
exudates occurred on day 50 of experiments with 40.36 mg.kg-1 pyrene
treatment. The greater the phytoremediation potential of the plant species
tested, the more obvious this trend wads. Compared with the control treatment
(CK), pyrene stress promoted the root system of all five species of
Festuca tested to release more low molecular weight organic acids, the
stronger the restoration potential of plant species, the higher the concentration
of pyrene stress under which the amount of organic acids in root exudates was
increased to the peak value. Among the five species of Festuca tested,
oxlic acid, acetic acid, lactic acid and malic acid were the main components of
organic acids in root exudates, with a percentage of greater than 98.15% in all
pyrene stress treatments, but there were traces of fumaric acid in the roots
secretion of plant species with the stronger restoration potential. Data also
indicated that 19 types of amino acids were found in root exudates of
Festuca and the composition of amino acids in root exudates of
Festuca was stable under all pyrene stress treatments, but the amino acid
amount was different in root exudates under pyrene stress. The amount of all
amino acids in those root exudates increased with increasing pyrene
concentration, especially, the amount of threonine, serine, glycine, and alanine
increased significantly among the 19 types of amino acids and the differences
were significant among different treatments with different pyrene concentrations
(P<0.05). However, proline, hydroxy proline and aspartic acid were always
released in the form of functional group as a response to the pyrene stress,
their contents soared quickly with the increase of stress concentration in soils,
and the difference was significant among different treatments with different
pyrene concentrations (P<0.05); the more the components of functional
group participated in stress response, the stronger the restoration potential of
plant species. These results indicated secretion characteristics of soluble
sugar, low molecular weight organic acids and amino acids in the root system were
closely related to their phytoremediation potential under the pyrene stress, the
greater the phytoremediation potential, the more the amount of these low
molecular weight secretions and the more complex these components, and the
stronger the adaptability to polluted environment and the physiological
plasticity to adapt to these contaminants.
PMID- 29964910
TI - [N% and S% in Leaves of Vascular Plants Cinnamomum camphora and Pinus
massoniana Lamb. for Indicating the Spatial Variation of Atmospheric Nitrogen
and Sulfur Deposition].
AB - N and S contents in Cinnamomum camphora leaves, Pinus massoniana
Lamb. leaves, epilithic Haplocladium microphyllum(Hedw.) Broth. and
rhizosphere soil collected along 3 directions from urban area to rural area at
Guiyang city in a total of 296 samples were investigated systematically. The
level of atmospheric N deposition and atmospheric SO2 concentrations at each
sampling site were calculated according to the quantitative relationship between
moss N content and atmospheric N deposition and the quantitative relationship
between moss S content and atmospheric SO2 concentration. Leaves N content in
Cinnamomum camphora(1.01%-2.37%) and Pinus massoniana Lamb.(0.99%
2.42%)showed significant decrease from urban area with the highest atmospheric
nitrogen deposition to suburb, while slightly higher leaves N reemerged at rural
area beyond 24 km, suggesting increased N deposition occurred in rural area.
Leaves S content in Cinnamomum camphora(0.16%-0.43%) and Pinus
massoniana Lamb.(0.18%-0.32%) showed significant decrease from urban area to
suburb, the highest level at urban was mainly contributed by the high sulfur
released from the production and living of urban areas into the atmosphere, and
the lowest level occurred at rural area(30-36km). No significant difference was
seen for soil N and S contents. The relationships between the estimated input of
atmospheric N deposition and the leaves N content of Cinnamomum camphora
and Pinus massoniana Lamb. at the sites investigated were found to be
significant linear correlations, and the relationships between the estimated
atmospheric SO2 concentration and the leaves S content of Cinnamomum
camphora and Pinus massoniana Lamb. were also significant linear
correlations(P<0.05). The results indicated that N and S contents in
Cinnamomum camphora and Pinus massoniana Lamb. leaves can be used
to show the spatial variation of atmospheric N and S deposition.
PMID- 29964911
TI - [Temporal and Spatial Dynamics of Greenhouse Gas Emissions and Its Controlling
Factors in a Coastal Saline Wetland in North Jiangsu].
AB - Although coastal wetlands play an important role in governing the atmospheric
concentrations of CO2, CH4, and N2O, thus control the global warming, research of
the greenhouse gas emissions conducted in the coastal wetlands were not well
documented because of the difficulty in fieldwork in these harsh environments,
and the complicated controlling factors affecting the greenhouse gas emissions.
The temporal and spatial variations of CO2, CH4, and N2O were investigated
simultaneously in the coastal saline wetland in North Jiangsu during the period
from April, 2014 to March, 2014, using the closed static dark chamber method. And
the results showed that seasonal variations of CO2, CH4, and N2O were higher in
summer, and lower CO2 and N2O fluxes were observed in winter, while for CH4 in
spring, it presented the sink in the coastal wetland. The annual average CO2
emission derived from the Spartina alterniflora flat (SAF) was the
highest, with the value of (766.3+/-496.9) mg.(m2.h)-1, and
for CH4 and N2O, the highest values were found in Phragmites australis
flat (PAF), with the values of (0.420+/-0.900) mg.(m2.h)-1
and (17.4+/-5.0) MUg.(m2.h)-1, respectively. The bare mud
flat (BF) presented the sink of CH4, and the source of CO2 and N2O, with the
lowest emission rates across all the tidal flats. The global warming potential
(GWP) from the coastal wetlands in north Jiangsu was observed higher in
SAF[68841.280 kg.(hm2.a)-1], which was 1.41 and 3.02 times
higher compared with those of PAF and SGF, the GWP of BF was the lowest, with the
value of 5002.100 kg.(hm2.a)-1. Furthermore, significant
correlations were found between CO2 fluxes and temperature, including air
temperature (AT), soil temperature (ST), and temperature inside the chamber (CT),
however, for CH4 and N2O, the correlations were not so obvious. Above all, the
temporal variations of CO2, CH4, and N2O were mainly controlled by the
temperature and characteristics of vegetation, the spatial variations of CO2,
CH4, and N2O were determined by the characteristics of vegetation. Furthermore,
we may safely draw the conclusion that the invasive S. alterniflora
increased the global warming potential dominantly through increasing the CO2
emission rates, compared with the native plant.
PMID- 29964912
TI - [Preparation of Visible-light-induced g-C3N4/Bi2S3 Photocatalysts for the
Efficient Degradation of Methyl Orange].
AB - Visible light responsive heterojunctions of graphitic carbon nitride (g-C3N4) and
Bi2S3 were successfully designed and constructed by a simple solvothermal
process. The as-prepared samples were characterized by X-ray diffraction (XRD),
Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy
(SEM), transmission electron microscopy (TEM), high resolution transmission
electron microscopy (HRTEM) and UV-vis diffuse reflectance spectroscopy (DRS).
Under visible light irradiation, the as-prepared g-C3N4/Bi2S3 photocatalysts
exhibited highly enhanced photochemical efficiency in the degradation of methyl
orange (MO) compared with pure g-C3N4 and Bi2S3. On the basis of the calculated
energy bands, the excellent enhancement was attributed to the efficient
separation of photoinduced electron-hole pairs. In addition, a detailed
degradation pathway of MO degradation by g-C3N4/Bi2S3 composites was proposed to
further elucidate the inner photodegradation mechanism. This research may provide
a cost-effective and easy-scaling up approach to develop visible-light-driven
photocatalysts, which could be applied in wastewater treatment.
PMID- 29964913
TI - [Estimation of Co-benefits from Pollution Emission Reduction by Eliminating
Backward Production Capacities in Hainan Province].
AB - Industrial structural adjustment plays a significant role in achieving the
pollution reduction goals in China. It is an optimal choice for Hainan Province
to promote industrial structure upgrading and build a "national demonstration
area for ecological civilization construction". The emission factor method was
used to estimate co-benefits of pollution emission reduction through closure of
backward production capacities as a result of industrial structural adjustment
policies. The results showed that in Hainan Province the cumulative reduction
emissions of NOx, dioxins and mercury were 2826.0 t.a-1,
10462.5 mg.a-1 and 280.8 kg.a-1 respectively from 2006 to
2013, taking into consideration of cement, iron & steel, paper making and solid
clay bricks sectors. The impact of eliminating backward production capacities on
reductions of NOx was not remarkable, but the impacts on control over
dioxins and mercury emissions were significant. The paper provided a new approach
for estimating co-benefits from reducing the conventional pollutants and emerging
pollutants.
PMID- 29964914
TI - [Evaluation and Development of a Weighing Chamber by Using Saturated MgCl2
Solution].
AB - In recent years, China has suffered a lot from atmospheric particles. Many
studies of particles are based on filters. As a result, the accuracy of filter
weighing is of great importance. A weighing chamber (1.2 m*0.6 m*0.8 m) was
developed and evaluated using saturated MgCl2 solution with a self-made flow
control system to maintain constant relative humidity (RH). By evaluating the
mass change of blank and aerosol-enriched filters after weighing in different RH,
we selected RH of 30%-40% as the range for the proper constant RH. To reach a
constant RH, 20 L.min-1 dry air was put through a RH-constant chamber with MgCl2
solution in it. Then, the RH-constant air was put continually into the weighing
chamber. After the weighing chamber reached stable RH, the flow rate was adjusted
to 5 L.min-1 to maintain the RH. Throughout a one-month test, the weighing
chamber maintained 30.1%-34.0% RH while the outside RH changed a lot. We weighed
60 filters with this weighing chamber after equilibration for 24 hours. The
standard deviation after three times' weighing was no more than 0.02 mg. compared
to other methods, the RH-controlling method of this weighing chamber was simple,
stable, easy to maintain, and cost effective.
PMID- 29964915
TI - [Characteristics Research on Carbonaceous Component of Particulate Matter Emitted
from Iron and Steel Industry].
AB - In order to investigate the carbonaceous characteristics of particles emitted
from the iron and steel industry, an electrical low-pressure impactor (ELPI) was
used to collect three sets of samples from the sintering process and one set of
samples from the ironmaking process emissions of particulate matters. Organic
carbon (OC) and elemental carbon (EC), which were divided into seven carbonaceous
components based on the temperature of the particulate matter, were analyzed
using a thermal-light reflection method. Results show that OC in sintering
process particles is higher than that in ironmaking particles and accounts for
5.3%+/-2.3% and 7.1%+/-3.0% of PM10 and PM2.5, respectively, which reveals that
OC tended to be enriched in fine particles. In the ironmaking process particles,
OC accounted for 2.5% and 2.0% of PM10 and PM2.5, respectively. The relative
proportions of the seven carbonaceous components in the four sets of samples were
very similar. OC2 and OC3 accounted for the highest proportion; the EC1, EC2, and
EC3 contents decreased in turn; and OC1 may be associated with boiler scale and
desulfurization. In addition, the OC and EC of sintering process particles had
higher correlation, and the OC/EC value of primary emission particles was 4.7+/
0.7, which is much higher than the value of the secondary OC estimation index in
environment. Analyzing deeply on the carbonaceous characteristics in particles
emitted from the iron and steel industry, which will provide essential data for
source apportionment of carbonaceous aerosols in environment and will be
conducive to the follow supervisory of pollution cleaning in iron and steel
industry.
PMID- 29964916
TI - [Pollution Characteristics and Source Identification of PAHs in Atmospheric PM2.5
in Changzhou City].
AB - A total of 55 ambient fine particle (PM2.5) samples were collected in Changzhou
City from January to August 2016. The concentrations of 17 PM2.5-bound PAHs in
the samples were analyzed by GC-MS. Results showed that seasonal average mass
concentrations of PAHs in winter, spring, and summer were 140.24, 41.42, and 2.96
ng.m-3, respectively, which indicating that the pollution of PAHs in winter
appeared more serious than in the other two seasons, and 4-6-ring high molecular
weight PAHs were predominant in all three seasons. The average daily level of BaP
was 3.64 ng.m-3 and the days it exceeded the permitted standard accounted for 41%
of total days. PAH concentration had significant negative correlations with
temperature (correlation coefficient: -0.643) and visibility (correlation
coefficient: -0.466), whereas it had good positive correlations with atmospheric
pressure (correlation coefficient: 0.544) and poor correlations with wind speed
and relative humidity. PAH concentrations were higher at nighttime than at
daytime, because of the influences of temperature difference, atmospheric
stratification, as well as pollution sources. The results from the air backward
trajectory model indicated that PM2.5-bound PAHs in Changzhou were mainly
affected by local emission sources and short-distance transportation, whereas the
contribution of long-distance transmission was small (only 11%). Based on
analysis of characteristic ratios, PAHs were mainly sourced from coal burning,
vehicle emissions, and biomass burning. An incremental lifetime cancer risk
(ILCR) model was used to evaluate the health impact of PAHs via breathing
exposure pathways. Results revealed that the ILCR of adults was higher than that
of children. The ILCRs of the group for winter and spring were slightly higher
than the risk threshold, but a difference was not obvious for summer.
PMID- 29964917
TI - [Atmospheric Dry Deposition Fluxes and Sources of Polycyclic Aromatic
Hydrocarbons in Lanzhou Valley, Northwest China].
AB - The atmospheric dry deposition flux pollution levels were determined and the
sources apportioned for 15 US EPA priority polycyclic aromatic hydrocarbons
(PAHs) collected at 13 sampling sites in the Lanzhou valley using passive
sampling techniques. The results are as follows. The annual atmospheric dry
deposition fluxes ranged from 7.48 to 53.94 MUg.(m2.d)-1, with a mean of 18.65
MUg.(m2.d)-1. The highest flux levels for both the heating and non-heating
seasons, 60.85 MUg.(m2.d)-1 and 47.03 MUg.(m2.d)-1, respectively, appeared at the
traffic site (Donggang Bridge), where the heaviest traffic in the Lanzhou valley
occurs. The lowest flux levels of 8.16 MUg.(m2.d)-1 and 6.80 MUg.(m2.d)-1 for the
heating and non-heating seasons, respectively, were found at Baita Mountain,
which has a higher percentage of vegetation cover. Meanwhile, the flux levels at
the background site (Guantangou Mountain) were significantly lower than those of
the other sampling sites. For dry deposition, the PAH components Phe, Flua, Flu,
and Pyr were dominant in the heating and non-heating periods, and the sums of the
percentages of 3- and 4-ring PAHs were 87.53% for the heating season and 82.73%
for the non-heating season. Moreover, the percentage of 5- and 6-ring PAHs for
the non-heating period was higher than that for the heating period, which may be
because the lighter PAHs were easily volatilized, and thus escaped. Furthermore,
the sources of atmospheric dry deposition were identified by principal component
analysis (PCA). The results of source apportionment showed that the main
atmospheric PAH dry deposition in the Lanzhou valley were from vehicle exhaust
emissions, coal combustion, and the coking industry. In further detail, coal
combustion and the coking industry contributed most of the PAH dry deposition
emissions during the heating period except for the traffic area site of Donggang
Bridge, whereas vehicle exhaust was the dominant contributor during the non
heating season. In addition, the annual average dry deposition velocities of
atmospheric PAHs were calculated using the dry deposition model for three sites:
0.20 cm.s-1 downtown (Environmental Protection Agency of Lanzhou; JCZ), 0.15 cm.s
1 in an industrial area (Lanyuan Hotel of Xigu; LLH), and 0.17 cm.s-1 in a
traffic area (the Staff Hospital of Gansu Province; ZGH), of which the latter two
were relatively lower because of comprehensive meteorological factors such as
wind speed, temperature, and land use categories. Regarding the dry deposition
flux values of the 3- and 4-ring PAHs, the simulated values were a bit larger
than the observed values, but all were at the same level of magnitude. However,
the simulated flux values were closer to their observed values for 4-ring PAHs
than for 3-ring PAHs, which indicated that 3-ring PAHs were lost more easily than
4-ring PAHs were during monitoring.
PMID- 29964918
TI - [Characteristics and Sources of Elements in Atmospheric Dust Fall in Zhuzhou
City, Central China].
AB - To study the concentration characteristics as well as sources of elements and
heavy metal pollution in atmospheric dust fall in Zhuzhou City, 144 samples from
12 sites in the Zhuzhou urban area were collected from January to December in
2012 and 28 kinds of elements in the samples were analyzed. The results showed
that the dust fall quantities of the industrial areas and mixed commercial and
residential (MCR) areas were, respectively, 89.46 g.m-2 and 33.20 g.m-2 and the
range of all sample points was 23.14-114.67 g.m-2. There were 10 elements (Na,
Mg, Al, K, Ca, Ti, Mn, Fe, Zn, Pb) in the industrial areas as well as 8 elements
in the MCR areas, for which the contents greatly exceeded 1000 mg.m-1 in the
atmospheric dust fall. The Zn and Pb contents exceeded 10000 mg.kg-1 in the dust
fall of the industrial areas, which were far higher than those in the Earth's
crust. The main sources of dust fall in Zhuzhou City were metal smelting, shallow
ground dust, vehicle emissions, construction dust, and industrial production with
specific elements (Mo, Ba). Correlation analysis, principal component analysis
(PCA), and analysis of transportation characteristics showed that 13 elements
(Mn, Fe, Co, Cu, Zn, As, Se, Ag, Cd, Sn, Sb, Tl, Pb) in dust fall mainly came
from waste gas emissions of industrial areas in Zhuzhou, in which 7 heavy metal
elements (Cu, Zn, As, Ag, Cd, Sb, Pb) caused serious pollution. The contents of
heavy metals in the industrial areas were 7.4 to 4079.4 times the contents
defined in China soil elements background values, whereas those in the MCR areas
were 3.6 to 1413.4 times the soil background values. Cd was the highest
background ratio element. The degree of contamination was clearly higher in the
industrial areas than in the MCR areas.
PMID- 29964919
TI - [Atmospheric Pollutant Emission Characteristics from the Cooking Process of
Traditional Beijing Roast Duck].
AB - As one of the characteristics of traditional food in Beijing, there is a
significant difference between roast duck and other foods in the cooking process,
in that fruit trees are used as fuel in the former. However, system research
about the emission characteristics of this food source has not been done
domestically. In order to grasp such food source emission characteristics and
provide technical basis for pollution control, we selected the representative
roast duck restaurant in Beijing and studied the emission characteristics of
atmospheric pollutants in the cooking process of roast duck. The results showed
that the emission concentrations of cooking fumes, particulate matter, volatile
organic compounds (VOCs), and aldehyde and ketone compounds were (0.74+/-0.45),
(15.32+/-7.93), (7.60+/-3.41), and (1.22+/-0.59) mg.m-3, respectively. The
emission concentration of particulate matter was much higher than that of cooking
fumes. The VOC component composition was very complex, containing alkanes,
alkenes, aromatic hydrocarbons, and oxygen VOCs, such as aldehydes, ketones,
alcohols, ester compounds, and halogenated hydrocarbons, with the highest
concentrations of 3-methylfuran, ethanol, and methyl acetate. The main components
of aldehyde and ketone compounds were acetaldehyde, formaldehyde, and acrolein,
of which C1-C3 compounds were 72.27%.
PMID- 29964920
TI - [Exhaust Emission Characteristics of Typical Alkanes from Heavy-Duty Diesel
Vehicles Based on a Portable Emission Measurement System].
AB - The on-road emissions of typical alkanes from 11 heavy-duty diesel vehicles with
different emission standards (from China I to China IV) were tested using a
portable emission measurement system(PEMS) and quantified by gas chromatography
mass spectrometry (GC-MS). Our aim was to analyze the emission characteristics of
typical alkanes in heavy-duty diesel vehicle exhaust. The results show that the
emission standard significantly affected the emission factors (EFs) of n-alkanes
and hopanes. Vehicles with higher emission standards had lower EFs. Compared with
China I vehicles, the total EFs of n-alkanes, 17alpha(H),21beta(H)-C30 hopane
(C30-hopane), and 22S- and 22R-17alpha(H),21beta(H)-homohopane (22S-C31 and 22R
C31 homohopane) from China IV vehicles were significantly reduced by 72.23%,
64.95%, 70.78%, and 74.68%, respectively. The peak carbon numbers of gaseous n
alkanes were 17 to 18, while they were 18 to 21 in particulate n-alkanes. The 22S
C31 homohopane/(22S-C31 homohopane + 22R-C31 homohopane) ratios ranged from 0.46
to 0.56, with an average of 0.50, which conform to the characteristics of hopanes
in petroleum. The total EFs of n-alkanes had a good linear relationship with the
total EFs of C30-hopane, and the R2 was 0.9268. Furthermore, the driving
conditions had a great influence on the emissions of n-alkanes and hopanes.
Specifically, the EFs of n-alkanes and hopanes on non-highway roads were 1.69 to
2.42 times greater than those on highways.
PMID- 29964921
TI - [PM10 Concentration Forecasting Model Based on Wavelet-SVM].
AB - PM10 is the main air pollutant in Taiyuan, as the city is a heavy industrial
center with coal as its main energy source. Therefore, research on the prediction
of this pollutant's variation and concentration is of great theoretical
significance for air pollution prevention and emergency solutions. The source of
PM10 is very complex, as it is affected by industrial emissions, vehicle exhaust,
fugitive dust, and many other factors. The emission sources of PM10 are difficult
to determine accurately. The goal of our research was to give accurate
forecasting results efficiently when only time-series PM10 concentrations, and no
other exogenous information, is available. A support vector machine (SVM) enjoys
good generalization performance in the PM10 concentration forecasting area.
Traditionally, an SVM chooses historical data as the input features in the
process of dealing with the time-series data of air pollutant concentrations.
However, data with simple structure and incomplete information have become the
fetter of generalization ability improvement. In this study, the data for
simulation experiments was the PM10 concentration dataset collected from four
monitoring stations in Taiyuan. The PM10 concentration time-series one-dimension
data was decomposed into high dimension, constructed by low frequency and high
frequency series using a wavelet transform. The wavelet-SVM forecasting model can
be established by introducing the high-dimension data as the input features. The
experiment results indicate that, contrasted with the traditional SVM, the
wavelet-SVM model boasts higher accuracy for PM10 concentration prediction. In
particular, it captures the concentration mutational points more accurately and
provides information support that is more effective for atmospheric pollution
warning. In addition, with the wavelet-SVM model, prediction accuracy for the
concentration variations was significantly improved and laws that were more
inherent in the PM10 concentration time series were revealed.
PMID- 29964922
TI - [Emission Factors and Preliminary Emission Estimates of Air Pollutants from Ships
at Berth in the Guangzhou Port].
AB - Three large container vessels over a tonnage of 40*103 t at berth in the
Guangzhou Port were selected for determination of air pollutants in exhausts from
auxiliary engines to obtain fuel-based emission factors (EFs). The fuel-based EFs
for vessels A, B, and C at berth were 3096, 3031, and 3028 g.kg-1, respectively,
for CO2; 61.8, 19.9, and 27.0 g.kg-1 for NOx; 8.0, 4.0, and 5.3 g.kg-1 for CO;
31.4, 41.9, and 56.7 g.kg-1 for SO2; 2.4, 1.1, and 1.5 g.kg-1 for PM2.5; and
0.13, 0.09, and 0.17 g.kg-1 for VOCs. With the basic information about ship
types, arrival times, and berthing times, the emissions of NOx, CO, SO2, PM2.5,
and NH3 from a ship at berth in the Guangzhou Port in 2014 were roughly estimated
to be 1231, 226, 1229, 47.6 and 0.04 t, respectively, with ships with a tonnage
of 10*103-50*103 t sharing the largest burdens, followed by ships over a tonnage
of 50*103 t. Estimated emission of VOCs from ships at berth in the Guangzhou Port
was about 33.6 t, with vessels below a tonnage of 3*103 t contributing the most.
PMID- 29964923
TI - [Influence of Dust Events on the Concentration and Size Distribution of
Microorganisms in Bioaerosols].
AB - In order to study the influence of dust events on the airborne microbes in
atmospheric bioaerosols, bioaerosol samples were continuously collected from
March to April 2015 during two dust events using size-fractionated bioaerosol
samplers in Lanzhou and Qingdao. The concentration of airborne microbes were
measured using an epifluorescence microscope after staining with DAPI (4',6
diamidino-2-phenylindole). The results showed that the concentration of airborne
microbes increased significantly during the period of dust (P<0.05). The average
concentrations of airborne microbes on sunny days were 5.61*105 cells.m-3 and
2.08*105 cells.m-3 in Lanzhou and Qingdao, respectively, whereas the mean
concentrations on dusty days were 14.8 times and 6.42 times those on sunny days,
respectively. The concentration of airborne microbes presented a bimodal size
distribution on sunny days in Lanzhou and Qingdao, with a peak at>7.0 MUm and the
lowest values ranging from 4.7 MUm to 7.0 MUm. However, the second peak appeared
at 3.3-4.7 MUm and 1.1-2.1 MUm in Lanzhou and Qingdao, respectively. The size
distribution of airborne microbes changed during the dust period. The size
distribution of microbes still presented a bimodal distribution in Lanzhou;
however, one peak shifted from>7.0 MUm to 1.1-2.1 MUm. The size distribution in
Qingdao changed from a bimodal distribution to a skewed distribution with the
predominant fraction in coarse mode. The background values of microbial load in
PM10 before the dust were 2224 cells.MUg-1 and 1550 cells.MUg-1 in Lanzhou and
Qingdao, respectively, and the highest value of such increased significantly to
26442 cells.MUg-1 and 10250 cells.MUg-1 during the dust events, respectively.
This demonstrated that the high concentration of microbes in the dust events
resulted not only from increased atmospheric particles but also from dust source
and transportation path along with long-range transported dust particles.
PMID- 29964924
TI - [Odor Emission Characteristics and Pollution Evaluation from Typical Household
Rubbish Disposal Facilities].
AB - In order to study the characteristics of odors from typical household rubbish
disposal facilities, samples were taken from pretreatment workshops of the
landfill process, incineration process, and composting process in Beijing, and
cold enrichment-GC/MS was used to determine the odor component qualitatively and
quantitatively. Results indicated that six categories were detected in all
samples: aromatic hydrocarbons, sulfides, halides, olefins, alkanes, and oxygen
containing organic substances. In the pretreatment workshop of the landfill
process, 50 kinds of chemicals were detected, the total odor concentration was
100.069 mg.m-3, the theoretical odor concentration was 350.611, and the
comprehensive odor index was 25.448. In the pretreatment workshop of the
incineration process, 55 kinds of chemicals were detected, the total odor
concentration was 36.052 mg.m-3, the theoretical odor concentration was 141.434,
and the comprehensive odor index was 21.506. In the pretreatment workshop of the
composting process, 34 kinds of chemicals were detected, the total odor
concentration was 25.382 mg.m-3, the theoretical odor concentration was 27.547,
and the comprehensive odor index was 14.401. Combined with the threshold of
diluted multiples, the particular pollutants of the pretreatment workshop of the
landfill process were dimethyl disulfide, butyl acetate, p-diethylbenzene, and
ethanol. Similarly, the particular pollutants of the pretreatment workshop of the
incineration process were methanethiol, dimethyl disulfide, ethanol, and
limonene. The particular pollutants of the pretreatment workshop of the
composting process were ethanol, dimethyl disulfide, butyl acetate, and limonene.
PMID- 29964925
TI - [Perfluorinated Compounds in Snow from Downtown Hangzhou, China].
AB - Snow samples were collected from the snow event on January 20-22, 2016 from 11
sites in downtown Hangzhou to explore the occurrence of sixteen perfluorinated
compounds (PFCs) in the atmosphere. All samples were prepared by solid-phase
extraction with Oasis WAX cartridges and analyzed using ultra performance liquid
chromatography interfaced with tandem mass spectrometry (UPLC-MS/MS). The results
showed that seven medium- and short-chain PFCs including C4 and C8 perfluorinated
sulfonates (PFSAs) and C4-C6, C8, and C9 perfluorinated carboxylic acids (PFCAs)
were detected in the snow samples. Total PFC concentrations ranged from 2.85 to
35.1 ng.L-1, whereas perfluorooctanoic acid (PFOA) dominated, with ranges of 2.15
23.0 ng.L-1, and perfluorooctane sulfonate (PFOS) was detected at lower levels,
ranging from 0 to 0.46 ng.L-1. As compared to the results from other studies, the
PFOA concentrations of the study region were at mid-level and the PFOS
concentrations were relatively low. The spatial distribution of PFCs varied, and
the pollutant concentrations of the snow samples from the sampling sites located
in the urban areas were higher than those in the rural areas. The greatest total
PFC concentrations were detected in Fuyang, whereas the lowest concentrations
were detected in Jiande and Chun'an. In this study, the high concentrations of
PFCs dominated by PFOA that were measured in the Hangzhou snow samples emphasize
the importance of atmospheric wet deposition as one of the sources of PFC
contamination in this ecological system and should be addressed. The occurrence
of PFCs in the air, indicated by their presence in the snow, suggests that the
atmospheric environment may be an important contributor in human and ecological
exposure to PFCs by local residents.
PMID- 29964926
TI - [Fluorescence Characterization of Fractionated Colloids in Wastewaters Received
by Huangpu River].
AB - The spectral characteristics of fractionated colloids in wastewaters from Huangpu
River were isolated and investigated via cross flow ultrafiltration systems with
different molecular mass of membranes and three-dimensional excitation-emission
matrix fluorescence spectroscopy. The results showed that the colloidal
concentration (CC) and colloidal organic carbon content (COC) of all size
fractions in all samples were in the ranges 9.60-32.50 mg.L-1 and 0.03-6.25 mg.L
1, respectively. Moreover, both CC and COC values increased as the colloidal size
increased. The protein- (i.e., peaks D and T) and humic-like (peaks C and A)
materials were present in all the size fractions (except for the Mr 300*103-1 MUm
size fraction of the influent sample), of which protein- and humic-like materials
were mainly in the Mr 1*103-5*103 and Mr 10*103-300*103 size fractions,
respectively. In addition, fluorescence indices (including the fluorescence index
(FI), humification index (HIX), and the index of recent autochthonous
contribution (BIX)) were introduced to determine the source and spectral
characteristic of the selected colloids. These indices indicated that the
relatively small colloids with high aromaticity and hydrophobicity mainly
originated from terrestrial sources, whereas the relatively large colloids were
predominantly from the recent autochthonous organic matter and the protein-like
components.
PMID- 29964927
TI - [Sources of Organic Carbon in the Surface Water of Lijiang River].
AB - This study selected a larger typical karst basin, that of Lijiang River, as the
research subject and studied the sources of organic carbon in the Lijiang basin
in July, August, and September in 2016 by an isotope tracer method, a
correlational analysis method, and endmember mixture model, using a stable
isotope of carbon and the organic carbon to nitrogen ratio. The results showed
the following. 1 The spatial distribution characteristics of DIC concentration
were as follows: karst area> karst and non-karst mixed area> non-karst area. The
content of DIC downstream was higher than upstream. The spatial distribution of
DIC concentration was mainly controlled by the distribution of carbonate rocks in
the Lijiang basin. 2 DOC was the main part of TOC in the Lijiang basin. TOC was
mainly derived from the primary productivity of aquatic organisms. The spatial
distribution characteristics of autochthonous organic carbon content were as
follows: karst area> karst and non-karst mixed area> non-karst area, which may be
related to more lush aquatic plants in the karst area than in the non-karst area
and the carbonic anhydrase activity in the karst area being higher than in the
non-karst area. The content of autochthonous organic carbon in the TOC ranged
from 1.02 to 5.14 mg.L-1, with an average of 2.54 mg.L-1. There was no
significant spatial difference of the proportion of autochthonous organic carbon
in the TOC; it ranged from 51.68% to 85.99%, with an average of 73.07%. 3 The POC
concentration, the content of autochthonous organic carbon in the POC, and the
proportion of autochthonous organic carbon in the POC had no significant spatial
differences. The main source of POC was allochthonous organic carbon, and the
content of autochthonous organic carbon in the POC ranged from 0.01 to 0.16 mg.L
1, with an average of 0.05 mg.L-1. The proportion of autochthonous organic carbon
in the POC ranged from 3.69% to 41.94%, with an average of 17.31%. 4 The spatial
distribution of the content of DOC and autochthonous organic carbon in the DOC
are as follows: karst area>karst and non-karst mixed area>non-karst area. DOC
mainly came from the primary productivity of aquatic organisms. The content of
autochthonous organic carbon of the DOC ranged from 0.97 to 5.10 mg.L-1, with an
average of 2.48 mg.L-1. The spatial distribution of the proportion of
autochthonous organic carbon in the DOC had no obvious difference and ranged from
54.43% to 94.69%, with an average of 79.51%. Studying the influence of aquatic
photosynthetic organisms on organic carbon in rivers can provide basis for
scientific problem solution of the stability of karst carbon sinks.
PMID- 29964928
TI - [Impacts of Thermal Stratification on the Hydrochemistry and Dissolved Inorganic
Carbon in a Typical Karst Reservoir in Summer].
AB - Thermal stratification leads to significant stratification characteristics of
hydrochemistry and aquatic organisms in reservoirs, and thus affects the
biogeochemical cycle in the reservoir. This study aims to understand physico
chemical properties and dissolved inorganic carbon change processes and its
factors in a karst groundwater-fed reservoir, Dalongdong Reservoir, located in
Shanglin County, Guangxi Zhuang Autonomous Region, China. The eight sampling
points were placed along the direction of the water flow on June 19-21, 2015. The
results show that: 1 The reservoir exhibited obvious thermal stratification in
the summer. There were significant differences in physical and chemical
parameters, such as pH and conductivity (Spc) between the epilimnion and
thermocline; 2 The dissolved oxygen (DO) and chlorophyll a (Chl-a) content from
the surface to the bottom did not show a single decreasing trend, but the maximum
value occurred 2.5 m or 5 m below the surface; 3 From the surface to the bottom,
dissolved inorganic carbon (DIC) concentrations showed an increasing trend with
the average DIC concentration of 2.03 mmol.L-1 in the epilimnion and the average
DIC concentration of 4.18 mmol.L-1 at the bottom of the thermocline. The value of
stable carbon isotope (delta13CDIC) was more positive in the epilimnion than in
the thermocline, where delta13CDIC gradually became partially negative with water
depth. Possible reasons of these results include: 1 The significant differences
in temperature, distribution of aquatic organisms, and strength and direction of
metabolisms in different water layers due to thermal stratification; 2 The DIC
variations in the epilimnion were mainly affected by the carbonate precipitation
process and phytoplankton photosynthesis, thereby affecting the DIC stable
isotope fractionation. DIC was mainly controlled by biological respiration and
the organic matter decomposition process in the thermocline.
PMID- 29964929
TI - [Comparison of Heavy Metal Contamination Characteristics in Surface Water in
Different Functional Areas: A Case Study of Ningbo].
AB - From industrial and commercial areas of Ningbo City, China, 85 surface water
samples were collected. The concentrations of six heavy metals (Cd, Cr, Cu, Ni,
Pb, and Zn) in the samples were measured, and the characteristics of the spatial
distributions of those metals were analyzed. Through a combination of regional
characteristics and Pearson correlation coefficients of the different heavy
metals, the main pollution sources of the two areas were analyzed. The potential
ecological risks of these heavy metals were evaluated by considering health risk
and cancer risk indices. The results indicate that the heavy metal pollution of
surface waters was serious in both the industrial and commercial areas.
Furthermore, the differences between the two areas were also observed. In the
industrial area, the average concentrations of the six heavy metals were, from
highest to lowest, in the order: Zn >>Ni>Pb> Cr> Cu> Cd, and the main sources
were industrial emissions. Four heavy metal concentrations exceeded the national
environmental standard, which, from highest to lowest, were in the order: Cd> Pb>
Cr >>Zn. In the commercial area, the average concentrations, from highest to
lowest, were in the order: Cr> Pb >>Zn> Ni> Cd> Cu, and the main sources were
road pollutants. Three heavy metal concentrations exceeded the national standard,
and the order, from highest to lowest, was Cd> Pb>>Cr, with Cd and Pb having the
most potential health risk. In both the industrial and commercial areas, there
were some potential health risks and high carcinogenic risks. Cd, Cr, and Pb have
the highest potential health risks, whereas Cr is the major potentially
carcinogenic metal. The commercial area had 1.7 times the potential carcinogenic
risk as that of the industrial area. The government should pay more attention to
heavy metal pollution of surface waters in Ningbo City, China.
PMID- 29964930
TI - [Comparison of Identification Methods of Main Component Hydrochemical Anomalies
in Groundwater: A Case Study of Liujiang Basin].
AB - Identification of chemical composition anomalies in groundwater is an important
basis for establishing groundwater background values and quantifying the degree
of influence of human activities. The main component anomaly identification by
five kinds of hydrochemical diagrams has achieved good results in the past.
However, this method is too complex to be used widely. In order to simplify the
five kinds of hydrochemical diagrams, the Durov diagram was used to replace the
five kinds of hydrochemical diagrams to identify the main component anomalies of
groundwater, with the Liujiang basin employed as a verification example. The
effects of seven kinds of anomaly identification methods combined by
hydrochemical diagrams and mathematical statistics methods were compared, and the
reliability of these methods were tested in the study. The result indicated that
the combination of mathematical statistics and hydrochemical diagrams method can
identify the groundwater anomalies better than either used alone. The method of
the Pauta criterion+five kinds of hydrography diagrams and the Pauta
criterion+the Durov diagram were the best to identify the major component
anomalies of groundwater. This shows that the Durov diagram can effectively
replace the five kinds of hydrochemical diagrams for anomaly recognition of
groundwater, which not only preserves the scientificity of hydrochemical anomaly
identification, but also greatly simplifies the process of calculation.
PMID- 29964931
TI - [Biotic and Abiotic Uptake of Phosphorus in Benthic Sediments of Suburban Streams
Under Intense Human Disturbance Scenario].
AB - To reveal the impact of land use change on the phosphorus uptake in benthic
sediments of suburban streams, a headwater stream in the urban fringe of Hefei
City was selected and a set of benthic sediments was collected monthly from the
chosen stream reach from June to November 2016. An incubation method was applied
to explore the biotic and abiotic uptake of phosphorus in benthic sediments under
intense human disturbance scenario. Results showed that the uptake potentials in
summer were higher than those in autumn, both for total (including biotic and
abiotic) and abiotic uptake of phosphorus. Furthermore, both of these uptakes
were distinctly higher for the third sampling site, which is adjacent to the
sewage outlet, than those for the other sites. For all six sampling sites, the
contribution rate of biotic uptake of phosphorus was significantly greater than
that of abiotic uptake, both in summer and autumn. The monthly variations in
potentials and contribution rates of phosphorus uptake indicated that intense
human disturbance via land use change had a great impact on the biotic uptake of
phosphorus in benthic sediments of the suburban stream.
PMID- 29964932
TI - [Sedimentary Phosphorus Speciation in the Coastal Hypoxic Area of Changjiang
Estuary and Its Environmental Significance].
AB - Phosphorus (P) is a potential limiting nutrient in Changjiang Estuary.
Sedimentary P preservation and regeneration play an important role in indicating
regional environmental changes and buffering P limitation in the water column. A
series of coring experiments was implemented in the hypoxic area of Changjiang
Estuary to explore sedimentary P speciation and distribution and their
environmental significance. The results showed that the contents and
distributions of P in the cores were largely influenced by terrestrial loading,
and Detr-P was the dominant P form in the sediments, followed by Org-P, Fe-P, and
Auth-P, whereas Exch-P was the minor phase of Tot-P (<5%). Auth-P was
predominantly yielded by Org-P and Fe-P transformations. P preservation in
Changjiang Estuary was significantly related to terrestrial inputs and
environmental changes in the water column. P speciation in cores tracked the
regional environmental changes effectively. Distribution of reactive P in the
hypoxic area was significantly different from that in the oxic area, with fairly
high C/P ratios. The benthic diffusive flux of DRP in the study area ranged from
0.90 to 1.13 MUmol.(cm2.a)-1. Tot-P burial efficiency (PBE) was higher than 70%
and the PBE for Detr-P was nearly 100%, whereas the PBEs for Fe-P and Org-P were
38% and 26%, respectively. Auth-P was the dominant fraction of reactive P
preserved in the sediments, and about 51% of Auth-P originated from Fe-P and Org
P transformations. The PBE in the hypoxia area of Changjiang Estuary was fairly
lower than that in the continental shelf of the East China Sea. Hypoxia leads to
a decrease in the PBE, which would have long-term influence on ecological
environmental problems, especially eutrophification. Changes in terrestrial
inputs played a key role in P composition in the sediments; the P loads of
Changjiang River coupled with primary production and hypoxia greatly affected the
P cycling in the Estuary.
PMID- 29964933
TI - [Characteristics and the Relationship of Nitrogen and Phosphorus in Soil and
Water of Different Land Use Types of a Small Watershed in the Three Gorges
Reservoir Area].
AB - Long-term field monitoring data was analyzed regarding the characteristics of
nitrogen and phosphorus in the soil and shallow groundwater of different land use
types in a typical small watershed of the Three Gorges Reservoir area.
Furthermore, the relationships among soil nitrogen and phosphorus contents,
concentrations of nitrogen and phosphorus in shallow groundwater, and slope
surface runoff were analyzed. The results showed that the average contents of TN
and NO3--N in terrace soil were significantly higher than those in sloping upland
soil (P< 0.05), for which the average content of paddy terrace was highest (1.49
g.kg-1). The average contents of TP in the soil of sloping upland and mulberry
sloping upland were significantly higher than those in the soil of other land
types. The average content of NO3--N in the soil of dryland terrace was highest
of all land use types and its discrete degree was also largest. The slope land
use type had greater impact on the concentrations of TN and NO3--N in shallow
groundwater, but it had little influence on TP concentration. In addition, the
shallow groundwater TN concentration and NO3--N concentration had significant
positive correlation, and the average contribution rate of NO3--N to TN in five
wells ranged from 67.82% to 78.51%. The monthly average concentration of TN and
NO3--N in shallow groundwater changed little, only showing a significant upward
trend after the fertilization stage of the two crops in spring and autumn. The
average contents of TN and NO3--N in the slope soil were significantly correlated
with the TN and NO3--N concentrations in the shallow groundwater, but there was
no significant correlation between the TN and NO3--N concentrations in the
surface runoff. When the slope surface runoff TP concentration was>0.1 mg.L-1,
the average content of TP had a significant linear correlation with it. There was
a significant power function relationship between the concentrations of TN and
NO3--N in the surface runoff and concentrations of TN and NO3--N in the shallow
groundwater, with higher correlation of NO3--N concentrations between surface
runoff and shallow groundwater.
PMID- 29964934
TI - [Characteristics of Carbon Transportation Under Rainfall Events and Associated
Carbon Loss Evaluation in Loess Plateau, China: A Case Study of Yangjuangou Dam
Watershed].
AB - In this study, by monitoring carbon transportation and its rainfall-runoff
process during the rainy season in Loess Plateau's Yangjuangou dam watershed, we
analyzed changes in carbon transportation driven by rainfall and further
evaluated the C loss flux for the dam watershed. Results showed that the monthly
C wet deposition flux for the wet and dry seasons were 3.33 kg.hm-2and 2.18 kg.hm
2, respectively, which were only small contributions to C transportation for the
watershed. C transportation under the rainfall-runoff process in this watershed
can reach 944.89 kg.km-2 and 300.29 kg.km-2 in August and September,
respectively. Different intensities of rainfall runoff lead to different C loss
processes, wherein dissolved inorganic carbon (DIC) is the main C form. Under
small rainfall events, the output of dissolved total carbon (DTC) in this
watershed was 156.98 kg.km-2; and the output of moderate rainfall events was
284.60 kg.km-2. Finally, we determined that the C loss modulus of the Yangjuangou
watershed was 1.89 kg.(km2.mon)-1 in the rainy season, thus the C loss modulus
for the study area could reach 2.70 kg.(km2.a)-1.
PMID- 29964935
TI - [New Bromated Phenolic Disinfection Byproducts: Mechanism of Their Decomposition
During Chlorination].
AB - Recently, 13 new phenolic halogenated disinfection by-products (DBPs) have been
reported in chlorinated drinking water and have been classified into four groups:
dihalo-4-hydroxybenzaldehydes, dihalo-4-hydroxybenzoic acid, dihalo-salicylic
acids, and trihalo-phenols. In this work, the four fully brominated species (3,5
dibromo-4-hydroxybenzoic acid, 3,5-dibromosalicylic acid, 2,4,6-tribromophenol,
and 3,5-dibromo-4-hydroxybenzaldehyde) were selected as representatives, and the
decomposition mechanism of these new DBPs during chlorination was studied with
the aid of ultra performance liquid chromatography/electrospray ionization triple
quadrupole mass spectrometry (precursor ion scan, multiple reaction monitoring,
and product ion scan). Except for 3,5-dibromosalicylic acid, the new DBPs were
not stable and could be finally decomposed to haloacetic acids through multistep
substitution, hydrolysis, and oxidation. Various decomposition intermediate DBPs
were detected, including a new group of halogenated DBPs with cyclic structures
(trihalo-hydroxyl-cyclopetene-diones).
PMID- 29964936
TI - [Effects of Algal Morphology and Al Species Distribution on the Coagulation
Ultrafiltration Process].
AB - In order to ensure drinking water quality, three different Al-based coagulants
[Al2(SO4)3(AS), Al13, Al30] were used to treat water laden with different algae
[Microcystis aeruginosa(cyanobacteria), Chlorella(green algae), Cyclotella
(diatoms)]. Floc size, strength factor, and recovery factor under different
conditions were measured to investigate the mechanisms in the coagulation
ultrafiltration process. The results indicated that the main mechanism in the
coagulation process using Al13 or Al30 as coagulants was electrostatic patching
and the main mechanism using AS was charge neutralization. In the Microcystis
aeruginosa and Chlorella systems, when Al13 and Al30 were used as coagulants at
low dosage, the coagulants that were adsorbed on the side (which existed on the
surfaces of Microcystis aeruginosa and Chlorella cells) would lose their ability
to aggregate the algal cells. When AS was used as coagulant, the electric double
layer was effectively compressed. The repulsive force between algal particles
decreased, and the flocs formed easily. In the Cyclotella system, Al13 and
Al30coagulants effectively formed the flocs through electrostatic patch effects.
There was a significant correlation between membrane flux and floc size, and the
larger flocs formed a looser cake layer on the membrane surface.
PMID- 29964937
TI - [Functional Group Characteristics of Planktonic Diatoms and Their Relationship
with Environmental Factors in the Ruxi River].
AB - To elucidate the functional group characteristics of planktonic diatoms and their
relationship with environment factors in the Ruxi River, multivariate statistical
analysis and functional group classification were conducted in this study. The
success pattern of a diatom functional group and its driving factor were analyzed
for the Ruxi River, a typical tributary of Three Gorges Reservoir, after the
phytoplankton community and environmental variables were investigated at three
different stages: level water period (April 2014), dry season (December 2014),
and wet season (July 2014), based on the characteristic of water level. The
results showed that there were 10 diatom functional groups in the Ruxi River: the
A, B, C, D, Lo, MP, P, TB, X3, and S1 groups, and among them, MP was the most
groups, but the dominant group was D group. Stepwise multiple regression analysis
indicated that rho(TN) in the water column was the primary factor significantly
affecting the densities in the normal water period, whereas turbidity,
alkalinity, and pH significantly influenced the functional group densities in the
normal water period. In the high water period, however, transparency was the most
important environmental factor affecting the functional group densities.
Additionally, the results of RDA analysis found that water temperature,
electrical conductivity (Spc), oxidation-reduction potential (ORP), rho(DO), and
rho(NO3--N) were the main environmental factors that influenced the diversity of
diatom functional groups in the Ruxi River. These results suggested that
functional groups could well reflect the habitat characteristics of the Ruxi
River and the effect of the nutrient element, nitrogen, to the success of
phytoplankton functional groups and changes of water quality in the Ruxi River
should be paid more attention.
PMID- 29964938
TI - [Spatiotemporal Variations of Chlorophyll a and Its Relationship to Environmental
Factors in Shiyan Reservoir].
AB - The spatial-temporal characteristics of chlorophyll a concentration[rho(Chla)]
were analyzed in Shiyan Reservoir, based on the monthly monitoring data from
April 2013 to June 2014. The correlation between rho(Chla) and key environmental
factors were also studied using correlation analysis and canonical correspondence
analysis.The results showed that rho(TChla) was 9.59-123.29 MUg.L-1, with an
average of 52.03 MUg.L-1. The rho(Chla) of cyanobacteria was 4.54-76.30 MUg.L-1,
with an average of 28.39 MUg.L-1. The rho(Chla) of bacillariophyta was 3.16-46.09
MUg.L-1, with an average of 15.02 MUg.L-1. The rho(Chla) of chlorophyta was 0.77
26.2 MUg.L-1, with an average of 8.62 MUg.L-1. Cyanobacteria was the primary
species from April to December in 2013 and May, June in 2014 while
bacillariophyta was the primary species in other months. The spatial
heterogeneity of rho(Chla) was unconspicuous and rho(Chla) decreased gradually
from south to north. There was a risk of algal blooming for the whole reservoir
during flood season and south part of reservoir in autumn. The storm runoff
pollutant washout was the leading cause of the spatial heterogeneity of rho(Chla)
in Shiyan Reservoir. Analysis revealed that water temperature was the most
important driving factor for seasonal succession of phytoplankton. Significant
correlation was found between rho(Chla) and surface runoff in flood season. TN:TP
was negatively related to phytoplankton biomass and phosphorus was the
restrictive factor for phytoplankton. Cyanophyta were affected water temperature,
TOC, TN, pH, transparency, turbidity and NO3--N. However silicate, TOC, NO3--N,
and COD were the main environmental factor of bacillariophyta while TOC, COD, pH,
transparency and NO3--N were the main factor of chlorophyta.
PMID- 29964939
TI - [Rhizosphere Microbial Diversity in Different Wetland Microcosms].
AB - To investigate the rhizosphere microbial community structure characteristics in
varying combinations of plants and filter materials in the process of aquaculture
pond water treatment, six types of wetland microcosms were established using two
kinds of plants (Zizania latifolia Turcz. and Sagittaria graminea) and two types
of filter materials (garnet and magnetite). High-throughput sequencing technology
was used to analyze the microbial structural features and composition diversity
of the wetland rhizosphere. The results were as follows. The microorganisms
recovered belonged to 52 phyla, 118 classes, 455 families, 905 genera, and 1426
species. Based on the Shannon index, Zizania latifolia Turcz. (average value:
5.77) had a higher capacity than Sagittaria graminea(average value: 5.29) in
terms of microbial enrichment. However, the rate of Proteobacteria in the
rhizosphere microorganism communities of the Sagittaria graminea and Zizania
latifolia Turcz. microcosms were 61.97% and 51.78%, respectively, further showing
that the roots of Sagittaria graminea in the wetland microcosms better enriched
the Proteobacteria during the experimental period. The major bacterial groups of
different plant roots were enriched with beta-Proteobacteria in the experiment.
The results of this study provide a theoretical basis for species optimization in
artificial wetland systems and best combination of wetland construction that will
be useful for future investigations.
PMID- 29964940
TI - [Community Structure of Microorganisms and Its Seasonal Variation in Beihai
Lake].
AB - Water samples were collected in summer, autumn, winter, and spring in Beihai Lake
for the analysis of water quality and microbial community structure. It was found
that the water quality in summer and autumn was worse than in winter and spring,
and TN and TP were the most important factors affecting the water quality. The
microbial community structure was investigated using MiSeq high-throughput
sequencing. It was found that the phyla Cyanobacteria, Proteobacteria,
Actinobacteria, and Bacteroidetes were abundant in all the samples, whereas their
relative abundances differed among the four seasons. In summer and autumn, the
microbial diversities were higher, and the phylum Cyanobacteria was most
abundant, with the genus Synechococcus dominant. In winter, the phylum
Proteobacteria was dominant. In spring, Actinobacteria and Bacteroidetes were
abundant, accounting for 51.5%-64.3% of the bacterial community. The redundancy
analysis (RDA) results showed that the microbial communities were mostly affected
by water temperature in Beihai Lake. Overall, the water quality of Beihai Lake
was qualified for the use of landscape water. However, the abundance of
Synechococcus in summer may lead to algal blooms. Thus, it is necessary to
strengthen the monitoring and estimation of water quality in Beihai Lake.
PMID- 29964941
TI - [Analysis of Microbial Diversity in a Fluidized-Sand Biofilter Based on High
Throughput Sequencing Technology].
AB - In order to understand the microbial community composition and mechanism of
purifying aquaculture water with a biofilter that was been applied to spotted
parrotfish recirculating aquaculture systems with microglass beads as the
biofilter filler, the changes in the nutrients of different biological filter
beds and the water treatment performance of a fluidized-sand biofilter were
analyzed. By using high-throughput sequencing technology, the microbial community
structure of the surface area and bottom area at different times were studied.
The results show that the fluidized-sand biofilter successfully start-up after
one month under marine culture. Nitrification of the biofilter occurred mainly in
the lower bed layer; the surface area played a small role in eliminating the NH4+
N. The average removal rates of NH4+-N, TN, BOD5, and SS were 68.3%+/-2.24%,
49.54%+/-3.56%, 60.35%+/-4.98%, and 45.21%+/-2.11%, respectively. The average
NH4+-N removal load reached (343.28+/-75.5) g.(m3.d)-1, which showed a better
performance of wastewater treatment. In this experiment, 31 phyla and 490 genera
were identified, thus the biological diversity was significantly higher than that
of the other conventional microbial biofilter. Start-stop cycling of the self
cleaning device in the biofilter had no effect on the microbial diversity of
different regional, but had some effect on the dominant bacterial community of
the microglass beads surface. Under opening self-cleaning device regularly
condition, the microbial species of the surface and bottom areas became
significantly similar. With time, the microbial species of the superficial area
and bottom area had no significant change, and the microbial population structure
was relatively stable. In the biofilm training period, the diversity of microbial
communities was significantly lower than it was after biofilm maturation. At the
time of biofilter stable operation, the dominant bacteria of the superficial zone
essentially remained unchanged and mainly included Anaerolineaceae_uncultured
(8.4%-28%), Flavobacteriaceae_unclassified (1.1%-32%),
Rhodobacteraceae_uncultured (2.3%-17%), Nitrospira(1%-7%), and
Caldilineaceae_uncultured (1%-6%). The dominant bacteria of the bottom zone
changed over time and mainly include Nitrospira (12.45%-17.06%),
Candidatus_Microthrix (2.6%-8.8%), Muricauda (4.8%-6.3%), Defluviimonas (6%-7%),
and Rhodobacteraceae_uncultured (2%-6.2%). Among them, the abundance of
Nitrospira was significantly higher than that in the other biofilter.
PMID- 29964942
TI - [Analysis of High-efficiency Denitrifying Bacteria and Embedding Filler
Performance and Microflora].
AB - In order to study adaptability and recovery capability of high-efficiency
denitrifying bacteria and their embedding filler to low temperature and low
substrate concentration, a test was performed under two conditions (favorable and
unfavorable) and three stages (D1, D2, and D3) to explore the denitrifying
capability of the bacteria. The favorable condition was a reacting temperature of
30C, a nitrate concentration of 300 mg.L-1, and a C/N ratio of 10; and the
unfavorable condition was a reacting temperature of 4C, a nitrate concentration
of 30 mg.L-1, and a C/N ratio of 5. In stage D1, high-efficiency denitrifying
bacteria [300 mg.(L.h)-1], which were cultured at favorable condition, were
placed under the unfavorable condition. In stage D2, the bacteria were embedded
after the denitrifying performance was stable, and then this embedded filler was
placed under the unfavorable condition and recovered in the favorable condition
(D3) after 90 days. The results show that the denitrification rates of stages D1
and D2 finally stabilized at 5.4 mg.(L.h)-1 and 4.8 mg.(L.h)-1, respectively,
after operation for 17 d and 16 d, indicating that the bacteria and their
embedding filler adapted to the unfavorable conditions of low temperature and low
substrate concentration. In stage D3, the denitrifying rate of the filler reached
300 mg.(L.h)-1 after operation for only 12 d, indicating that the filler had
rapid self-recovery capability. Scanning electron microscopy (SEM) was utilized
to analyze the internal and external structures of the embedding filler and it
was determined that both the internal and external structures were favorable for
bacterial growth metabolism and mass transfer. The high-throughput sequencing
analysis results show that the dominant genera in stage D2 were still
Pseudomonas, Thauera, and Gelidibacter, which have denitrifying functions,
thereby indicating adaptability of the bacteria under the unfavorable condition.
The dominant genera Thauera, Petrimonas, and Pseudomonas of the embedding filler
in stage D3 were identical to the dominant genera of the high-efficiency
denitrifying bacteria cultured under the initial favorable condition, which also
showed that the bacteria embedding filler had good recovery capability.
PMID- 29964943
TI - [Selection of Microalgae for Biofuel Using Municipal Wastewater as a Resource].
AB - Cultivating microalgae using municipal wastewater can achieve not only treatment
of the wastewater but also recovery of algae for use as a biofuel energy source.
Wastewater provides necessary nutrients, such as nitrogen and phosphorus, and
water for microalgal growth. Because of the complexity of components of municipal
wastewater, variety of adaptability, and tolerance to wastewater of different
microalgal species, it is necessary to select a suitable microalgal species with
high performance in lipid production and identify proper pretreatment of the
wastewater to achieve high lipid production using municipal wastewater for algal
biofuel production. Based on microalgal growth, lipid production, and clean-up
performance of wastewater, we selected Scenedesmus obliquus wild strain and
Chlorella pyrenoidosa mutant by ion beam implantation from a test group for the
biofuel production. Laboratory test results showed that S. obliquus wild strain
and C. pyrenoidosa mutant had respective lipid productions of 0.43 g.L-1 and 0.33
g.L-1, with more C16-C18 fatty acids, which were suitable for biodiesel
production. The pollutant removals from the wastewater by S. obliquus wild strain
and C. pyrenoidosa mutant were COD, 86.4% vs. 81.8%; NH4+-N, 100.0% vs. 100.0%;
TN, 94.3% vs. 94.9%; and TP, 93.4% vs. 94.2% respectively. The two different
microalgal strains required different pretreatments. After removal of large
particles, the raw wastewater could be directly used for the cultivation of S.
obliquus wild strain. To grow C. pyrenoidosa mutant with municipal wastewater,
pretreatment procedures including precipitation followed by filtration should be
employed.
PMID- 29964945
TI - [Combination of Microbubble Catalytic Ozonation and Biological Process for
Advanced Treatment of Biotreated Coal Chemical Wastewater].
AB - A combination of microbubble catalytic ozonation and biological process was used
for advanced treatment of biotreated coal chemical wastewater (BCCW). The
performance of the combination system and the influence of the ratio of ozone
dosage to influent COD were investigated. The results indicated that the
refractory nitrogen-containing aromatics in the BCCW was degraded efficiently by
microbubble catalytic ozonation, which resulted in some COD removal, ammonia
nitrogen release, and significant improvement of biodegradability. The ozone
utilization efficiency was close to 100% and the off-gas ozone did not need to be
treated. Sufficient dissolved oxygen (DO) was provided by the microbubble
catalytic ozonation for biological treatment without aeration. COD and ammonia
nitrogen were removed further in the biological treatment efficiently. Better
performance of the combination system was achieved when the system effluent
reflux ratio was 30% and the ratio of ozone dosage to influent COD was 0.44 mg.mg
1. In this case, for microbubble catalytic ozonation, the COD removal efficiency
was 42.5%, the ratio of ozone consumed to COD removed was 1.38 mg.mg-1, and the
ozone utilization efficiency was 98.0%. For biological treatment, the COD removal
efficiency was 42.3%. For the combination system, the total COD removal
efficiency was 66.7%, the average final effluent COD concentration was 91.5 mg.L
1, and the estimated total ratio of ozone consumed to COD removed was 0.68 mg.mg
1, indicating better technical and economic performance.
PMID- 29964944
TI - [Purification Effect of Piggery Wastewater with Chlorella pyrenoidosa by
Immobilized Biofilm-Attached Culture].
AB - Piggery wastewater treatment with microalgae is a biological recycling
technology. To evaluate the purification effect, this study investigated the
treatment of piggery wastewater at different dilution ratios with Chlorella
pyrenoidosa by attached cultivation and lipid production of algae cells and
explored the tolerance of Chlorella pyrenoidosa to the piggery wastewater, which
has high ammonia nitrogen. The piggery wastewater was diluted with purified water
1-, 2-, 5-, and 10-fold in culture media. The removal efficiencies of COD,
ammonia nitrogen, total nitrogen, and total phosphorus and the enrichment effect
of the heavy metals copper, zinc, and iron were measured. Meanwhile, we
investigated the lipid production of Chlorella pyrenoidosa in variously diluted
wastewater (1-, 2-, 5-, and 10-fold). It turned out that the purification effects
of COD, ammonia nitrogen, total nitrogen, and total phosphorus were best when the
piggery wastewater was diluted 5-fold, and the removal efficiencies were 86.8%,
94.1%, 85.2%, and 84.3%, respectively. Correspondingly, the lipid content was as
high as 32.7%, and the removal efficiencies of the heavy metals copper, zinc, and
iron were 72.9%, 70.0%, and 73.0%, respectively. The biomass productivity was
4.21 g.(m2.d)-1 at the end of the experiment. This research makes an effective
connection between microalgae and piggery wastewater, which is difficult to
purify deeply, and provides a theoretical basis for achieving algal biofuel
production and decreasing the cost of wastewater treatment.
PMID- 29964946
TI - [Effect of pH Shock on Nitrogen Removal Performance of Marine Anaerobic Ammonium
Oxidizing Bacteria Treating Saline Wastewater].
AB - The effect of pH shock on nitrogen removal performance of marine anaerobic
ammonium-oxidizing bacteria (MAAOB) treating saline wastewater was studied by
employing an ASBR reactor. Dynamic characteristics of the MAAOB were simulated by
the Andrew model and Ratkowsky model. The results indicated that the reactor had
the best nitrogen removal efficiency when the pH value was 7-8. The nitrogen
removal rate (NRR) was (0.30+/-0.04) kg.(m3.d)-1, and the total nitrogen removal
efficiency (TNRE) was (76.73+/-5.74)%. When the pH value was 8.5, FA had a mean
concentration of 14.22 mg.L-1 and little effect on nitrogen removal. The NRR was
(0.30+/-0.02) kg.(m3.d)-1. However, NO2--N accumulated and it was not completely
removed. When the pH values were 6.5 and 9, the concentrations of FA were 0.22
mg.L-1 and 37.84 mg.L-1, respectively, the NRRs were (0.10+/-0.02) and (0.15+/
0.02) kg.(m3.d)-1, and the TNREs were (23.04+/-9.88)% and (42.12+/-5.52)%. The
tolerance of the MAAOB in alkaline condition was stronger than that in acidic
condition. The Andrew model was modified to determine the relationship between
NRR and FA. Other parameters such as NRRmax, kS, and kI were also achieved
simultaneously. These are key to describing the nitrogen removal process of
MAAOB.
PMID- 29964947
TI - [Removal of Nitrogen from Alcohol Wastewater by PN-ANAMMOX].
AB - An integrated partial nitrification anaerobic ammonia oxidation reactor was used
to explore the feasibility of nitrogen removal from recycled ethanol wastewater.
The results show that the integrated partial nitrification-anaerobic ammonia
oxidation (PN-ANAMMOX) reactor was started successfully after 40 d under the
conditions of pH 7.8+/-0.5, temperature 30-35C, and aerobic ORP value 120-150 mV.
The total nitrogen removal rate of 0.125 kg.(m3.d)-1 increased to 0.75 kg.(m3.d)
1, Inoculation of mature nitrosated biofilms and anaerobic ammonium oxide
granules can accelerate the start of the reactor. The effects of alcohol
wastewater on the PN-ANAMMOX reactor were mainly caused by biodegradable TOC, The
biodegradable TOC concentration of 100mg.L-1 in alcohol wastewater can reduce the
removal rate of total nitrogen from 0.75 kg.(m3.d)-1 to 0.25 kg.(m3.d)-1,this
inhibition can be restored. Different concentrations of alcohol wastewater were
dosed into the PN-ANAMMOX reactor to acclimate the bacteria. The total nitrogen
removal rate first decreased and then increased, as the influent concentration
gradient increased, which was beneficial for improving the efficiency of nitrogen
removal by extending the HRT and increasing the dissolved oxygen in the PN stage.
Finally, the nitrogen removal rate stabilized at 0.65 kg.(m3.d)-1. These results
show that PN-ANAMMOX can be used for the treatment of alcohol wastewater.
PMID- 29964948
TI - [Biorecovery of Palladium from Simulated Wastewaters and Its Catalytic Property
for Methylene Blue].
AB - By using Enterococcus faecalis Z5 strain (CCTCC M2012445) as a microbial
resource, this study explored the possibility of recovering palladium (Pd) in the
form of nanoparticles by adding an electron donor; investigated the Pd
biorecovery efficiency of three kinds of simulated wastewaters including
industrial waste processing leachates (IW) , printed circuit board scrap (PCBS) ,
and spent automotive catalyst (SAC); and analyzed the effect of other metal ions
contained in simulated wastewater on Pd biorecovery efficiency. The results
showed that the E. faecalis Z5 could recover Pd(II) as palladium nanoparticles
from the three simulated wastewaters. X-ray diffraction and transmission electron
microscopy analysis indicated that the recovered product was Pd nanoparticles
that were about 10 nm in size and mainly distributed in the periplasm of the
cells. The order of Pd(II) biorecovery efficiency from the three kinds of
wastewaters was IW> SAC> PCBS. The biosorption efficiencies for IW, SAC, and PCBS
were 99.8% (6 h), 99.7% (8 h), and 90.3% (12 h), respectively, and the
bioreduction efficiencies were 99.9% (4 h), 99.9% (6 h), and 80.4% (36 h). Other
metal ions contained in the simulated wastewaters such as Pt(IV), Au(III), Ag(I),
Cu(II), and Fe(II) affected both the biosorption and bioreduction processes. The
degree of matrix effects on the Pd(II) bioreduction efficiency were in the order
Au(III)> Pt(IV)> Cu(II)> Ag(I)> Fe(II). Further doping the recovered Pd
nanoparticles with ferriferous oxide enabled the products to catalyze the
degradation of methylene blue in heterogeneous Fenton reactions, which showed
96.7% degradation rate of methyl blue within 80 min.
PMID- 29964949
TI - [Investigation of Initiation and Shock Process of ANAMMOX Based on Color Space].
AB - Anaerobic ammonia oxidation (ANAMMOX) is an efficient and energy-saving
denitrification technology, but it still lacks a simple and easy method to
characterize its start-up process and stable state. Based on the analysis of
water quality, color space was used to monitor the color change of sludge during
the start-up of ANAMMOX, and the species and quantity of microbial flora were
analyzed by high-throughput sequencing technology. The results were as follows. 1
According to water quality characteristics, the whole start-up process can be
divided into activity lag phase, activity enhancement period, load increase
period, and stable operation period. At the same time, HSV and CIELAB color space
indicators decreased first, then increased, and finally remained stable. The
change of sludge color was consistent with the change of water quality and the
change of dominant bacteria based on the molecular biology testing, which implies
correlations among these three. Therefore, color space can be used to
characterize the start-up process of ANAMMOX. 2 When subjected to shocks caused
by high load, H, S, a*, b*, Cab*, and TIN volume removal rate all decreased,
while Hab suddenly increased. The impact characteristic of the system was
accurately expressed by all of the color indicators. This paper proposes a color
space-based method for characterizing all phases of the start-up of ANAMMOX and a
shock process index system that provides a theoretical basis for applying color
space in ANAMMOX systems.
PMID- 29964950
TI - [Fast Start-up of Shortcut Nitrification in a CSTR and an MBR].
AB - In order to achieve fast start-up of shortcut nitrification, a continuous stirred
tank reactor (CSTR) and a membrane bioreactor (MBR) were selected for a
comparative study about the start-up characteristic of shortcut nitrification.
The differences in three aspects of the two reactors were investigated, namely
start-up time, nitrogen transformation, and sludge performance. The results
showed that the start-up of shortcut nitrification was successfully achieved in
the CSTR and MBR after 44 and 56 days of operation, respectively, with influent
C/N=1, temperature around 30C+/-1C, pH of 7.5-8.0, and dissolved oxygen (DO) of
0.6-1.0 mg.L-1, as well as combining anoxic/aerobic ratio 1:3 (15 min:45 min)
with shortened hydraulic retention time (HRT). The start-up period of the MBR was
shorter. On the 14th, 28th, and 56th day, the average nitrite accumulation
efficiencies in the CSTR were 51%, 66%, and 89%, respectively, and 50%, 71%, and
93% in the MBR, and nitrate formation rates of the CSTR was successively 7.4,
4.0, and 1.7 mg.(g.h)-1 (NO3--N/MLVSS), respectively, and 7.6, 3.5, and 1.0
mg.(g.h)-1 (NO3--N/MLVSS) for the MBR. A higher nitrite accumulation efficiency
and a lower nitrate formation rate were detected in the MBR on the 28th and 56th
day, respectively, which could be beneficial to the fast start-up of shortcut
nitrification. During the operation period, the shortcut nitrification sludge in
the two reactors was yellow, the sludge volume index (SVI) was between 55 and 110
mL.g-1, and the mixed liquor volatile suspended solids (MLVSS)/mixed liquor
suspended solids (MLSS) ratio was around 0.6-0.8. The good sludge performance
created favorable conditions for the fast start-up of shortcut nitrification in
both the CSTR and MBR. In conclusion, the MBR exhibited better performance in the
fast start-up of shortcut nitrification.
PMID- 29964951
TI - [Conversion Pathways of Substrates in Sulfate-Reducing Ammonia Oxidation System].
AB - The phenomenon of simultaneous transformation of ammonium and sulfate under the
conditions of inoculating ANAMMOX culture has gotten the attention of
researchers. However, there are some problems and doubts reported in the related
literature. In this study, the characteristics of ammonium and sulfate
synchronous transformation were investigated in a CFSTR via inoculation with
ANAMMOX culture. Under the condition of oxygen removal and non-filling, in the
unfilled sealed fermentation tank, the average conversion of NH4+-N was 50.8 mg.L
1 while that of sulfate-sulfur was 4.5 mg.L-1. Elemental analysis results showed
that the observed yellow solid was not elemental sulfur but rather iron
containing compounds. However, no obvious change of ammonium was observed when
using a filled sealed batch reactor. Only sulfate transformed significantly, and
the transformation rate was affected by the inoculation biomass. Under these two
conditions, the ORP in the reactor was completely different. This is an
indication that the synchronous transformation of ammonium and sulfate observed
in both our study and other related studies is probably not a process mediated by
ANAMMOX organisms, in which sulfate acted as the electron acceptor to oxidize
ammonium. Actually, ammonium and sulfate transformation were completely
independent: ammonium oxidation is due to the micro oxygen environment created by
the reactor operation form, whereas sulfate conversion is attributed to the
sulfate heterotrophic reduction that results from the organic matter release via
microbial decay. This transformation can clarify and explain the problems and
doubts reported in the related research.
PMID- 29964952
TI - [Effect of Different TOC to NH4+-N Ratios on Nitrogen Removal Efficiency in the
ANAMMOX Process].
AB - The effect of the TOC to NH4+-N ratio on nitrogen removal rate in an ANAMMOX
sequencing batch reactor was studied for the short term and long term. Short-term
results showed the maximum TOC/NH4+-N that ANAMMOX could afford was 1.4. At the
same time, the rate of nitrogen removal was 0.26 kg.(m3.d)-1. The maximum
nitrogen removal rate of 0.34 kg.(m3.d)-1 was obtained when TOC/NH4+-N was less
than 0.4 in the long-term experiment. Whereas the nitrogen removal rate of the
reactor decreased continuously when TOC/NH4+-N exceeded 0.4, and it was difficult
to recover the activity of the ANAMMOX bacteria in the short term. qPCR results
showed that the amount of ANAMMOX bacteria dropped from 2.9*1011 copies.mL-1 to
3.15*1010 copies.mL-1 with the increase of organics. When TOC/NH4+-N exceeded
1.6, NH4+-N could hardly be removed by the ANAMMOX bacteria, which were severely
inhibited. The number of denitrifying bacteria was 3.0*109 copies.mL-1;
meanwhile, most of the NO2--N in the reactor was removed via denitrification.
PMID- 29964953
TI - [Effects of Salinity on the Operation of EGSB Reactors and the Anaerobic Granular
Sludge].
AB - The existence of high concentrations of salinity and organics would have a great
impact on the microorganisms when using bioreactors to treat wastewater. Thus, it
is necessary to find bioreactors resistant to high concentrations of salinity.
The effect of salinity on an expanded granular sludge bed reactor (EGSB) was
studied by increasing the Cl- concentration from 0 to 10000 mg.L-1 using
simulated high salinity wastewater with a COD volume loading of 3.267 kg.(m3.d)
1. The results show no obvious inhibitory effect of Cl- on the microorganism when
the concentration of Cl- was below 7500 mg.L-1. Above 1.3 m3.(m3.d)-1 volumetric
gas production rate was maintained and COD removal rate could achieved 98.1% when
the Cl- concentration up to 7500 mg.L-1 while the large particle size of
anaerobic granular sludge occupying the majority of of the system. The anaerobic
granular sludge was seriously affected when the Cl- concentration as 10000 mg.L
1. The community structure of the anaerobic granular sludge was analyzed using
high-throughput sequencing when the Cl- concentration was 0 and 5000 mg.L-1. The
results show that the salinity stress produced different dominant groups. The
dominant species were Methanobacterium, Methanospirillum, Methanothrix, and
Paludibacter when the Cl- concentration was 5000 mg.L-1, but Methanoregula and
Longilinea were the dominant species when the Cl- concentration was 0.
PMID- 29964954
TI - [Start-up of Granule CANON Process and the Strategy for Enhancing Total Nitrogen
Removal Rate].
AB - To shorten the start-up time of the CANON granular sludge process and improve the
total nitrogen removal rate in the engineering, the start-up method of CANON
granular sludge process and the strategy for enhancing the total nitrogen removal
rate were studied in an SBR reactor. During the experiment, the temperature was
controlled at 30C+/-1C and the pH was 7-8, the aeration rate and settling time
were operated according to the sludge properties and effect of nitrogen removal.
The results showed that the transition of the sludge properties from combined
floc-granule to granule was realized after 55 d. The total nitrogen removal rate
reached 0.32 kg.(m3.d)-1 and remained stable after 117 d, thus the reactor was
started up successfully. With constant improvement of the aeration rate, the
average NRR was maintained at 1.35 kg.(m3.d)-1 after 77 d and improvement of the
process load was achieved. The results showed that there was good correlation
between the NRR and DO, therefore, the NRR can be determined by observing the DO
and the process can be maintained stably.
PMID- 29964955
TI - [Effect of Extracellular Polymeric Substance (EPS) on the Adsorption of
Perfluorooctane Sulfonate (PFOS) onto Activated Sludge].
AB - The adsorption of PFOS by activated sludge and EPS-removed sludge was conducted
to investigate the adsorption mechanism of activated sludge and the effect of EPS
on this adsorption process. The experimental results indicated that the
adsorption process of PFOS onto activated sludge and EPS-removed sludge fitted
the pseudo-second-order model, with equilibrium absorption capacities (qe) of
0.46 mg.g-1 and 0.38 mg.g-1, respectively. The sorption isotherm accorded well
with the Freundlich, Langmuir, and Temkin models. Chemisorption played an
important role in the adsorption of PFOS on the activated sludge. Ca2+ and Cu2+
contributed to PFOS adsorption on the activated sludge through an ion-bridging
effect. Adsorption efficiency was better on the normal activated sludge compared
to the EPS-removed sludge. FTIR and XPS were used to analyze the variations of
functional groups before and after sorption. The results showed that the amount
of functional groups such as hydroxyl, carboxyl, and amidogen on EPS-removed
sludge was lower; however, these functional groups were found to have
participated in the PFOS adsorption process. It is concluded that carboxyl and
amidogen contained in protein of EPS provided reaction sites for PFOS adsorption,
thus EPS components played a vital role in PFOS adsorption on the activated
sludge.
PMID- 29964956
TI - [Characteristics of N2O and NOx Emissions from Purple Soil Under Different
Fertilization Regimes].
AB - N2O and NOx emissions from a winter wheat-summer maize rotation system in purple
soil were measured on a long-term fertilization platform of purple soil for two
consecutive cropping years (from November 2014 to September 2016) by using a
closed-chamber and gas chromatography-based system. Chemical fertilizer (NPK),
pig manure (OM), incorporation of crop residues plus synthetic NPK fertilizer
(RSDNPK), pig manure plus synthetic NPK fertilizer (OMNPK), and nitrification
inhibitor with NPK fertilizer (DCDNPK) under the same rate of total nitrogen were
involved in monitoring N2O and NOx emissions. Short-term fertilizer-free
treatment (CK) was used as a control for emission coefficient calculation. The
results showed that N2O emission peaks appeared in the early stage of
fertilization and in the period of heavy rainfall for all fertilization regimes.
The NOx emission process was similar to that of N2O, in that emission peaks
appeared at the early stage of fertilization, yet no obvious emission peaks were
observed during heavy rainfall. The annual cumulative emissions of N2O from NPK,
OM, RSDNPK, OMNPK, and DCDNPK were 1.35, 4.38, 1.43, 2.46, and 0.92 kg.hm-2,
respectively, and the emission coefficients were 0.33%, 1.41%, 0.36% 0.73%, and
0.18%. The annual emissions of NOx from NPK, OM, RSDNPK, OMNPK, and DCDNPK were
0.11, 0.38, 0.10, 0.27, and 0.04 kg.hm-2, respectively, and the cumulative
emission coefficients were 0.03%, 0.13%, 0.03%, 0.09%, and 0.01%. Amendment of
organic material was the main stimulator for N2O and NOx emissions, as they
significantly increased 226% and 262% (for OM) and 83% and 157% (for OMNPK),
respectively (P<0.01), compared with conventional synthetic fertilizers. The
application of synthetic fertilizers combined with nitrification inhibitor
(DCDNPK) significantly reduced N2O emissions 32% and NOx emissions 62% (P<0.01),
whereas straw returning with NPK application increased N2O emissions 6% and
reduced NOx emissions 5% (P>0.05). Furthermore, statistical analyses showed that
soil inorganic N content was the main regulating factor of N2O and NOx emissions
together, whereas soil water-filled pore space (WFPS) and temperature were the
respective main regulating factors of N2O and NOx emissions individually.
PMID- 29964957
TI - [Effect of Plastic Film Mulching on Methane Emission from a Vegetable Field].
AB - Using the static opaque chamber method and choosing a chili-radish cropping
system, a field experiment, located in the Key Field Station for Monitoring of
Eco-Environment of Purple Soil of the Ministry of Agriculture of China in the
farm of Southwest University in Chongqing, was conducted in situ for one year.
Mulching and non-mulching treatments were set in the field, and the seasonal
variation of CH4 flux and CH4 concentrations in the soil profile and the seasonal
changes in soil moisture and temperature were observed for different treatments
to explore the effect of plastic film mulching on soil moisture and temperature.
The results showed that plastic film mulching can significantly improve the
surface soil temperature during the pepper growing season in spring and summer
(P<0.01), but no significant difference was seen during the radish growing season
in autumn and winter (P>0.05). The soil moisture of the plastic film mulching
treatment was significantly higher than that of no mulching in the radish growing
season (P<0.05), but no significant difference was observed for the pepper
growing season (P>0.05). During the whole observation period and under the
condition of plastic film mulching and conventional planting, the CH4 flux from
soil had no significant seasonal variation under all treatments, and the mean CH4
fluxes were -7.64 MUg.(m2.h)-1 and -9.00 MUg.(m2.h)-1, respectively. The
cumulative CH4 emissions for plastic film mulching and conventional planting were
-0.54 kg.hm-2 and -0.64 kg.hm-2, respectively, in the whole observation period,
and all the treatments showed a net absorption of CH4 for the whole observation
period. The results showed that the plastic film mulching could weaken the
ability of CH4 as a sink of the CH4 for the whole observation period. The CH4
concentrations in different soil profiles were in the order 10 cm>20 cm>30 cm,
and the concentrations of CH4 change patterns in different soil layers were
almost identical during the whole observation period. The CH4 concentrations at
the depths of 20 cm and 30 cm under the plastic film mulching soil were
significantly lower than those under no mulching soil (P<0.05), but no
significant difference was observed for the depth of 10 cm (P>0.05). Correlation
analysis showed that, under the plastic film mulching conditions, CH4 flux and
the 5 cm geothermal showed significant positive correlation (P<0.05), but CH4
flux and soil moisture showed significant negative correlation (P<0.05). However,
under the conventional cultivation conditions, there were no correlations between
CH4 flux and the 5 cm geothermal or soil moisture. There was also significant
positive correlation between CH4 concentration in the 10 cm and 20 cm depth soil
layers with the CH4 concentration in surface soil (P<0.01), and the CH4
concentration in the 30 cm depth soil layer had significant positive correlation
with the surface soil temperatures and the 5 cm geothermal. There was no
significant correlation between soil CH4 concentration and soil water content.
PMID- 29964958
TI - [Responses of Soil Ammonia Oxidizers to Simulated Warming and Increased
Precipitation in a Temperate Steppe of Inner Mongolia].
AB - Soil ammonia oxidizers, as key players for the ammonia oxidation process in soil
N cycling, could respond, adapt, and give feedback to global change. In this
research, soil samples were collected from a long-term field experiment with
increased precipitation and warming in a temperate steppe of Inner Mongolia. We
analyzed the responses of the abundance, diversity, and community structure of
ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) to warming
and increased precipitation using quantitative real-time PCR, terminal
restriction fragment length polymorphism (T-RFLP), and clone library. The results
showed that increased precipitation significantly stimulated soil pH and warming
significantly reduced soil respiration (SR). No significant difference was
detected regarding the abundances of amoA genes across all treatments, whereas
increased precipitation significantly affected the community structure of soil
AOB. However, the interactive effect between warming and increased precipitation
had no significant influence on the community structure of soil ammonia
oxidizers. The result of the structural equation model indicated that the plant
diversity and community structures of soil ammonia oxidizers were significantly
correlated, suggesting that there were certain relationships among climate
change, microbes, and plants. In conclusion, this study confirmed that soil
microorganisms had the ability to adapt to climate change, which could provide
important information for predicting future changes in ecosystems.
PMID- 29964959
TI - [Nitrification Activity and Autotrophic Nitrifiers in Long-term Fertilized Acidic
Upland Soils].
AB - Soil microcosm incubation, molecular ecology techniques including denaturing
gradient gel electrophoresis and Illumina MiSeq high-throughput sequencing, and
bioinformatics analysis were carried out to investigate the effect of long-term
fertilization with chemical fertilizers (NPK) and organic manure (OM) on soil
nitrification activity and the autotrophic nitrifying communities in acidic
upland soils. No fertilization soil (CK) was the control. Relationships between
soil nitrification activities, autotrophic nitrifying communities, and soil
characteristics were further evaluated. Long-term fertilization significantly
increased the soil organic carbon and inorganic nitrogen contents. Fertilization
with organic manure significantly increased soil pH and total nitrogen contents,
but decreased soil C/N. Autotrophic nitrification dominated soil nitrification,
and accounted for 73.60%-85.32% of total nitrification. Fertilization
significantly increased soil autotrophic nitrification activity and the highest
value was observed in the OM soil. During the microcosm incubation, the absolute
abundances of amoA genes and the relative abundances of 16S rRNA genes of ammonia
oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in the OM soil
significantly increased. The relative abundances of 16S rRNA genes of the AOA
greatly increased in both CK and NPK soils. These results suggested the
remarkable activity of AOA in the three soils (the predominant population was
Nitrososphaera,>99.30%) and implied that AOB was active in the OM soil (the
predominant population was Nitrosospira,>99.99%). We also found the activity of
nitrite-oxidizing bacteria (NOB) in the OM soil, and the predominant population
was Nitrospira (>96.69%). Stepwise regression analysis demonstrated that soil
autotrophic nitrification activity was significantly affected by soil total
nitrogen content, whereas the abundances of archaeal and bacterial amoA genes
were significantly affected by soil organic carbon content and soil pH,
respectively. We also found significant positive correlation between the relative
abundance of Nitrososphaera and soil nitrate content and a negative correlation
between the relative abundance of Nitrosospira and Nitrospira with soil C/N.
Overall, our results showed that long-term fertilization greatly increased soil
nitrification activity and altered the autotrophic nitrifying communities in
acidic upland soils. Soil autotrophic nitrification activity was significantly
stimulated by soil total nitrogen content. The Nitrososphaera group played a
critical role in nitrification of acidic upland soils. The increased soil pH and
decreased soil C/N stimulated the growth of Nitrosospira.
PMID- 29964960
TI - [Effects of CaCO3 Application on Soil Microbial Nitrogen Cycle in an Acid Soil].
AB - Soil nitrification and denitrification are important steps in closing the
nitrogen cycle. Understanding the effects of CaCO3 application on the
physicochemical properties and nitrogen cycle in acid soil would provide some
theoretical and technical information for stable and sustainable utilization of
this agricultural soil. In this study, a field trial was conducted in Xiangtan
city, Hunan province. In this field, the soil pH was 5.54, and CaCO3 was applied
at four levels: 0, 2.25, 4.5, and 7.5 t.hm-2. After one season of rice
cultivation, the soil was sampled to determine dissolved organic carbon (DOC),
NH4+-N, and NO3--N levels, and the potential nitrification rate (PNR) and
denitrifying enzyme activity (DEA) were measured. The results showed that CaCO3
application improved the content of soil DOC (762.10-868.58 mg.kg-1) and PNR
[0.59-0.82 MUg.(g.h)-1]. However, excessive application of CaCO3 (7.5 t.hm-2)
revealed an obvious inhibition on the activity of soil nitrification.
Furthermore, the result of Pearson correlation analysis indicated that soil
nitrification was positively correlated with soil DOC and negatively correlated
with NH4+-N content, whereas denitrification had a significant positive
correlation with NO3--N content and soil DOC, but a negative correlation with
water content.
PMID- 29964961
TI - [Responses of Extracellular Enzymes to Nitrogen Application in Rice of Various
Ages with Rhizosphere and Bulk Soil].
AB - Ecological enzyme activities are closely relevant to the carbon and nitrogen
decomposition and mineralization of paddy soils, which can reflect the growth and
metabolism of microorganisms. In order to clarify the response to nitrogen
application by different enzymes in the rhizosphere and bulk soil of rice, the
rhizosphere and bulk soil were identified using a rhizosphere bag. In addition,
the beta-1,4-glucosidase (BG) enzyme; beta-1,4-N-acetylglucosaminidase (NAG)
enzyme; and the effects of the rhizosphere, nitrogen application, and growth
period on soil enzyme activities were analyzed. The results showed that the
activity of the BG enzyme decreased by 7.4-13.5 nmol.(g.h)-1 in the jointing
stage and increased by 7.0-31.4 nmol.(g.h)-1 in the maturity stage, and the
activity of the BG enzyme in the rhizosphere and bulk soil also changed with the
growth period of rice.compared with no nitrogen fertilizer, nitrogen application
increased NAG enzyme activity by 1.1 times and rhizosphere soil by 0.3 times in
the bulk soil in the maturity stage. Nitrogen application and growth period had
significant effects on soil BG enzyme activity, whereas the interaction within
rice growth stage, nitrogen application, and rhizosphere effect had significant
effects on NAG enzyme activity. The result of RDA showed that the soil microbial
biomass carbon (MBC) and dissolved organic carbon (DOC) contents mainly affected
the activity of extracellular enzymes in the rice rhizosphere soil, whereas the
activities of enzymes in the rhizosphere soil were mainly affected by microbial
biomass nitrogen (MBN) and NH4+-N. The relationships between soil enzyme activity
and various factors are complex, and the effects of nitrogen addition on
microbial community composition needs to be considered after accounting for plant
physiological characteristics, soil enzyme activity, and soil characteristics.
PMID- 29964962
TI - [Variation in the Temperature Sensitivity of Surface Litter Respiration and Its
Influencing Factors].
AB - Surface litter respiration is a major component of soil respiration in the carbon
cycle of terrestrial ecosystems, and studying the variation in the temperature
sensitivity of surface litter respiration and its influencing factors is
important for the accurate understanding of the regional soil carbon cycle. In a
typical locust plantation (Robinia pseudoacacia L.) ecosystem in a small
watershed in Wang Donggou of Loess Plateau, China, three surface litter control
treatments were established: 1 control treatment, 2 litter removal treatment, and
3 doubled litter treatment, for studying the interannual variation (2009-2013) in
the temperature sensitivity of surface litter respiration and its influencing
factors. The interannual variability in the temperature sensitivity of surface
litter respiration was statistically significant (P<0.05). It ranged from 4.15 in
2012 to 6.67 in 2010, with mean value of 5.10 and a coefficient of variation of
19% in the control treatment, and from 1.77 to 6.52, with mean value of 3.36 and
a coefficient of variation of 56% in the doubled litter treatment. It was closely
related with annual surface litter biomass, annual mean soil moisture content,
and the interplay between annual surface litter biomass and annual mean soil
moisture content (P<0.01). Moreover, the contribution to temperature sensitivity
of surface litter respiration from soil moisture was greater than that from
surface litter biomass (control treatment: 2.68 vs. 2.04, respectively; doubled
litter treatment: 1.37 vs. 0.69, respectively). Additionally, under the doubled
litter treatment, temperature sensitivity of surface litter respiration decreased
by 34%. In the artificial locust plantation ecosystem, over 50% of surface litter
carbon was kept under the control treatment [215 g.(m2.a)-1 vs. 113 g.(m2.a)-1],
but only 24% of surface litter carbon was kept under the doubled litter treatment
[430 g.(m2.a)-1 vs. 326 g.(m2.a)-1], which implied that the soil carbon reserves
in the plantation ecosystem will not increase with an increase of surface litter
biomass in the Loess Plateau, China. Therefore, investigating the relationships
among soil moisture, surface litter biomass, and surface litter biomass control
measures are useful for the accurate understanding of the regional soil carbon
cycle.
PMID- 29964963
TI - [Magnetic Properties of Farmland Soils in Arid Regions in Northwest China and
Their Environmental Implications].
AB - In order to understand the feasibility of environmental magnetism methods in
farmland soil pollution monitoring in the northwest arid areas of China, the
environmental magnetic properties of 102 farmland soil samples from four typical
agricultural regions, namely Linze county, Ganzhou district, Minle county, and
Shandan county in Zhangye City were systematically analyzed. The results show
that the main magnetic mineral of farmland soil samples is ferrimagnetic
magnetite, and the main magnetic grain sizes are coarse-grained pseudo single
domain (PSD) and multidomain (MD), mainly between 0.2-1 MUm in equivalent
diameter. The low frequency magnetic susceptibility (chilf) value of farmland
soil samples ranged from 22.27*10-8 m3.kg-1 to 188.36*10-8 m3.kg-1, with the
average value of 63.85*10-8 m3.kg-1. Overall, the magnetic mineral content of
farmland soil samples was low, but it had large spatial variation. The spatial
distribution of the magnetic parameters show that the magnetic mineral contents
in Ganzhou district, Minle county, and Shandan county are higher than in Linze
county, and three relatively high-value areas are present in central Ganzhou
district, the southwest side of Minle county, and the west side of Shandan
county. High magnetic value in central Ganzhou district is mainly controlled by
human activities, such as industrial production, whereas the high magnetic values
in the southwest side of Minle county and west side of Shandan county are more
related to strong natural pedogenesis. Therefore, systematic comprehensive
analysis of magnetic parameters can effectively distinguish and delimit the man
made pollution range in farmland soil and provide a basis for farmland soil
pollution prevention and control.
PMID- 29964964
TI - [Preparation of Magnetic Biomass Carbon by Thermal Decomposition of Siderite
Driven by Wheat Straw and Its Adsorption on Cadmium].
AB - C-Fe3O4 composite material [magnetic biomass char (MBC)] was prepared by
pyrolysis of a mixture of wheat straw and siderite at 500C. The MBC was
characterized by XRF, FTIR, XRD, SEM, XPS, and a magnetic susceptibility device.
The effect of contact time, pH value, initial Cd2+ concentration, and ionic
strength on the adsorption capacity of the MBC to Cd2+ was investigated. The
results showed that the BET surface areas of the MBC and biomass char (BC) were
23.38 m2.g-1 and 7.20 m2.g-1, respectively, total pore volumes were 1.04*10-1
cm3.g-1 and 2.23*10-2 cm3.g-1, and average pore diameters were 17.74 nm and 12.38
nm. The magnetic susceptibility of the MBC was 42900*10-8 m3.kg-1. FTIR showed
that phenolic hydroxyl and carboxyl functional groups bound metal ions on the
surface of the MBC and BC. The kinetic data of the MBC were described well by the
pseudo-second-order model. Isothermal adsorption of Cd2+ by MBC and BC was fitted
well by the Freundlich equation. The adsorption velocity increased with an
increase of pH in the region 3-6 and then stabilized in the region 6-9. The
adsorption capacity of Cd2+ decreased slightly when ionic strength increased from
1 mmol.L-1 to 100 mmol.L-1, whereas the desorption rate increased from 0.51% to
8.5%. The adsorption properties and characterization results illustrated that the
removal mechanism of Cd2+ likely was through adsorption and ion exchange on the
surface of the MBC with a high amount of functional groups. In addition, magnetic
adsorbents offered a significant advantage compared to other adsorbents in the
aspect of separation from aqueous solution.
PMID- 29964965
TI - [Effects of Traffic-related Air Pollution Exposure on DNA Methylation].
AB - The goal of the present study was to explore the effects of traffic-related air
pollution exposure on DNA methylation. Into five groups of 6, 30 healthy Wistar
rats were randomly divided. Three groups of rats were then exposed to traffic
related air pollution at high (tunnel), moderate (crossroad), and low (control)
pollution levels for 7 d, whereas the two other groups were exposed in the tunnel
for 14 d/28 d. The levels of PM10 and NO2 were measured during the exposure. The
study was performed in spring and autumn, and lung tissue and blood were
collected after the exposure. Promoter methylation levels of p 53 , MGMT, and
MAGE-A 4 were quantified via pyrosequencing. The levels of PM10 and NO2 in the
crossroad and tunnel groups were significantly higher than those in the control
group. After 7 d exposure in autumn, promoter methylation levels of p 53 and MGMT
in lung tissue significantly decreased, and the methylation status continued to
decrease with increasing exposure time; MAGE-A 4 was highly methylated and showed
no difference among the three groups. DNA methylation in lung tissue was more
likely to be changed compared with that in blood during 7 d exposure. As the
exposure time increased, DNA methylation changes between blood and lung tissue
started to coincide. In lung tissue, PM10 exposure was significantly associated
with decreased p 53 promoter methylation (r=-0.347, P=0.038) and NO2 exposure was
significantly associated with decreased promoter methylation of p 53, MGMT, and
MAGE-A 4 (r=-0.482, -0.444, and -0.346, respectively; P< 0.05). In blood, PM10
and NO2 were significantly and positively associated with MAGE-A 4 promoter
methylation (r=0.395 and 0.431, respectively; P< 0.05). Traffic-related air
pollution exposure may induce promoter hypomethylation of p 53 and MGMT.
PMID- 29964966
TI - [Effects of Exogenous Microorganism Inoculation on Efficiency and Bacterial
Community Structure of Sludge Composting].
AB - In this study, municipal sludge, sawdust, and mushroom residues were used as raw
materials for composting, and thermophiles and white-rot fungi were added into
the compost in stages. By measuring physicochemical factors, including
temperature, pH value, organic matter, water-soluble organic carbon, moisture
content, total nitrogen, NH4+-N, NO3--N, and germination index during the
composting process, the effect of exogenous bacteria inoculation on the
efficiency of compost was determined. By means of high-throughput sequencing
technology, the variation of bacterial community structure and the impact of
exogenous bacteria inoculation on bacterial community structure during sludge
composting were also investigated. The results showed that the inoculation
extended the high temperature duration, decreased the nitrogen loss, and
accelerated the decomposition and detoxification of the compost. During the
entire period of composting, the structure of bacterial community changed
significantly. There was low similarity of bacterial community structure among
different stages of the same composting, but high similarity was observed in
different composting of the same period. The inoculation of thermophilic bacteria
improved the abundance of bacterial community and increased the proportions of
dominant genera in thermophilic phase, but changed no species of dominant genera.
Canonical correspondence analysis showed that pH had the highest influence on the
structure of bacterial community and that temperature possessed positive
correlation with nine genera.
PMID- 29964967
TI - [Life Cycle Assessment of Traction Lead-acid Batteries for Electric Bikes in
China].
AB - This research undertook a life cycle assessment (LCA) for lead-acid batteries
(LABs) used in electric bikes, the fastest growing LABs in China. A cradle-to
grave LCA model was established to identify the key materials or processes that
contribute most to environmental impacts within the life cycle of LABs, including
material production, battery manufacture, transportation, use, and end-of-life. A
large amount of primary data obtained from enterprisers and a Chinese LCA
database were used in this research to reflect the status of technology and
environmental management for the related industries in China. The results
indicate that material production and LAB use dominate in resource consumption
and environmental impacts during the life cycle of LABs. Material production is
the most important driver of such impacts as abiotic resources depletion (699%),
eutrophication (89%), photochemical smog production (98%), ozone depletion
(117%), total human toxicity (159%), and ecological toxicity (484%). Battery use
is responsible for 83% of primary energy use and contributes the highest
potentials to the impacts related to energy, including global warming potential
(86%) and acidification potential (70%). Recovery of materials at the end-of-life
stage will significantly mitigate the overall life cycle impacts by reducing
virgin material consumption. Based on the findings, there are several substantial
opportunities to reduce the overall environmental impacts of batteries, such as
prolonging the lifetime of batteries, reducing the metal consumption in
batteries, and improving the technology and management in recovery of end-of-life
batteries.
PMID- 29964968
TI - [Air Pollutant Emission Inventory from Iron and Steel Industry in the Beijing
Tianjin-Hebei Region and Its Impact on PM2.5].
AB - The iron and steel industry, which discharges a large amount of pollutants
including SO2, NOx, and PM2.5, is the main source of atmospheric pollution in the
Beijing-Tianjin-Hebei region. Based on the bottom-up method, a high temporal and
spatial resolution emission inventory of the iron and steel industry in the
Beijing-Tianjin-Hebei region was developed, which took into account the multiple
air pollutants released during coking, sintering, pelletizing, ironmaking,
steelmaking, and the steel rolling process. As the emission inventory showed, the
total emissions of SO2, NOx, TSP, PM10, PM2.5, CO, and VOC from the iron and
steel industry in the Beijing-Tianjin-Hebei region in 2015 were 388.2, 272.3,
791.9, 531.5, 386.8, 8233.8, and 265.3 kilotons, respectively, among which,
sintering and pelletizing were the two processes discharging the most pollutants
(17.0%-72.0%), followed by the ironmaking process (4.6%-42.4%) and the steel
rolling process (3.5%-35.7%); the iron and steel industry in Tangshan discharged
the most pollutants (39.1%-63.5%) among those in all the 13 cities. The impact of
the iron and steel industry on the regional PM2.5 concentration was simulated by
a two-layer nested meteorology-air quality coupling model system (WRF-CMAx) with
Particulate Source Apportionment Technology (PSAT). The simulation results showed
that the iron and steel industry contributed 14.0%, 15.9%, 12.3%, and 8.7% of the
PM2.5 concentrations of the Beijing-Tianjin-Hebei region in spring, summer,
autumn, and winter, respectively, and that the iron and steel industry had the
most significant impact on the PM2.5 concentrations in Tangshan among all the 13
cities, with a contribution rate up to 41.2%, followed by those in Qinhuangdao,
Shijiazhuang, and Handan, with contributions of 19.3%, 15.3%, and 15.1%,
respectively. The iron and steel industry has an important impact on the PM2.5
concentration of the Beijing-Tianjin-Hebei region to which the government should
pay more attention, and take more effective control measures to address this
problem.
PMID- 29964969
TI - [Simulation of the Spatio-temporally Resolved PM2.5 Aerosol Mass Concentration
over the Inland Plain of the Beijing-Tianjin-Hebei Region].
AB - In recent years, haze pollution in China is becoming increasingly serious,
especially in the Beijing-Tianjin-Hebei region. In order to identify the temporal
and spatial distributional characteristics of PM2.5 aerosol mass concentration in
the region, this study selected the inland plain of the Beijing-Tianjin-Hebei
region as the research area, and used MODIS AOD as the main predictor in a mixed
effects model to establish the daily relationship of AOD-PM2.5 in the study area,
from 2013 to 2014. The model was validated by a ten-fold cross validation method.
The results showed that the correlation between AOD-PM2.5 can be improved by
daily calibration of the mixed effects model (R2=0.78); the cross-validated R2
was 0.70, and RMSE and RPE were 20.80 MUg.m-3 and 28.76%, respectively.
Considering the importance of unbiased PM2.5 predictions, the correction factors
calculated from the surface PM2.5 measurements were applied to correct the biases
in the predicted annual average PM2.5 concentrations introduced by non-stochastic
missing AOD measurements. The results showed that the annual average
concentration of PM2.5 in the study area was higher than 75 MUg.m-3, and the
spatial distribution of PM2.5 concentration was higher in the southern and
western regions, and lower in the northern and eastern regions. These results
suggest that the mixed effects model can be used to monitor ground PM2.5, and
also provide a scientific basis for the control of atmospheric particulate
pollution in the region.
PMID- 29964970
TI - [Effect of Relative Humidity on Particulate Matter Concentration and Visibility
During Winter in Chengdu].
AB - The effect of relative humidity (RH) on particulate matter concentrations and
atmosphere visibility were investigated using the continuous on-line observed
data of Chengdu city during December 2015, including RH, visibility, the
concentrations of particulate matters (PM10, PM2.5 and PM1) and gaseous
pollutants (SO2 and NO2), and the concentrations of SO42- and NO3- in PM2.5. The
results showed that the haze process occurred because of the synergistic effects
of higher particulate matter concentrations and RH, leading to the reduction of
visibility. The average ratio of PM2.5 to PM10 was 64% and it significantly
increased with the increase of RH during observation period, which indicated that
the pollution of fine particles during winter in Chengdu was serious, and high RH
aggravated the pollution caused by fine particles.Visibility decreased
exponentially with the increase of particulate matter concentrations. When RH was
higher, visibility was lower at the same concentrations of particulate matter.RH
had a strong effect on visibility at lower particle concentrations, while the
effect of RH on the visibility decreased, and atmospheric extinction was
controlled by PM2.5 concentrations at higher particle concentrations. With RH
increasing from less than 40% to more than 70%, the average sulfur oxidation
ratio (SOR) and nitrogen oxidation ratio (NOR) increased from 0.27 and 0.11 to
0.40 and 0.19, respectively, indicating that higher RH significantly promoted the
formation of secondary sulfate and nitrate. Secondary sulfate and nitrate
separately or coordinatively influenced the air quality.
PMID- 29964971
TI - [Vertical Distributional Characteristics of Inorganic Ions of PM2.5 at Mt.
Huashan, Inland China].
AB - PM2.5 was simultaneously collected using a high-volume sampler at 4 h intervals
from the mountainside and the foot of the mountain in the Mt. Huashan region,
inland China, during the summer of 2016, and the samples were analyzed for
inorganic ions, to investigate the chemical characteristics and vertical
distribution of the fine particles in the region. The results showed that the
concentrations of PM2.5 were (46.9+/-38.2) MUg.m-3 and (76.0+/-44.3) MUg.m-3 on
the mountainside and at the foot of Mt. Huashan, respectively. The concentrations
of inorganic ions in PM2.5 was higher at the foot of the mountain than on the
mountainside, with the order of the mass concentrations of the major ionic
species being SO42- > NO3- > NH4+ > Ca2+. Among all the inorganic ions, SO42-,
NO3-, and NH4+ are the dominant species, accounting for 89% and 85% of the total,
on the mountainside and at the foot, respectively. The fine particulate NH4+
existed mostly in the forms of (NH4)2SO4 and NH4NO3 on the mountainside, and in
the forms of NH4HSO4 and NH4NO3 at the foot of the mountain. Mass concentrations
of PM2.5 and its major components on the mountainside showed clear diurnal
variations, with maximums between 12:00-16:00, mainly due to the transport of the
pollutants from the ground surface by the planetary boundary layer height
variation and the valley breeze. In contrast, the diurnal variations of PM2.5 and
its major components at the foot are characterized with two maxima, peaking
between 08:00-12:00 in the daytime and 00:00-04:00 in the nighttime,
respectively, mainly due to the increased emissions from both the morning rush
hour traffic and the nighttime on-road heavy-duty vehicles. Acidity of the fine
particles was estimated by using the equivalent ratio of anions to cations and
the thermodynamic equilibrium model ISORROPIA II. Both methods showed that the
acidity of PM2.5 at the ground surface site is stronger than that on the
mountainside in the Mt. Huashan region.
PMID- 29964972
TI - [Analysis of the Composition of Atmospheric Fine Particles (PM2.5) Produced by
Burning Fireworks].
AB - Burning fireworks is one of the sources of atmospheric fine particles (PM2.5).
The Chinese Spring Festival in Quanzhou City was taken as an example to study the
effects of burning fireworks on the occurrence of PM2.5, and provide information
on protection against air pollution caused by special pollution sources. The
results showed that the concentrations of SO2, PM10, and PM2.5 increased
appreciably, and the concentration of PM2.5 increased most significantly during
the fireworks burning period. The peak daily average concentration in the urban
area was about 4 times the annual average concentration in the urban area. The
peak value of the hourly average concentration of PM2.5 in the Tushan Street
station was about 21 times the annual average concentration in the urban area. At
the peak of the discharge, the ratios of the characteristic elements of
fireworks, such as Al, Mg, Ba, Cu, and Sr, increased rapidly, and the hourly
number concentrations of Al+, Mg+, Ba+, and Cu+ were highly correlated. During
the monitoring period, the main pollution sources of fine particles in Quanzhou
City were fireworks and biomass burning, which accounted for more than half of
the total particulate matter. The proportion of pollutants originating from coal
based and industrial process sources were relatively low, and both of them
accounted for less than 10.0% of the particulate matter. The concentration of
PM2.5 was up to 0.578 mg.m-3 during the fireworks burning period, the rate of
contribution by fireworks increased to 58.2%. Analysis of the pollution process
showed that the changes in the concentration of PM2.5 have a similar trend with
the number concentration and the ratio of fireworks burning. The results
indicated that the main reason of the deterioration of the atmospheric
environment during the Chinese Spring Festival in Quanzhou is the centralized
discharging of fireworks.
PMID- 29964973
TI - [Chemical Composition Characteristics of PM2.5 Emitted by Medium and Small
Capacity Coal-fired Boilers in the Yangtze River Delta Region].
AB - Seven small and medium coal-fired boilers were selected to analyze the emission
factors and chemical composition characteristics of PM2.5, and the efficiency of
the dust collection unit in removing PM2.5, OC, and EC of different particle
sizes. At the outlet of the dust collection unit, PM2.5 mass emission factor was
around 0.047-0.283 g.kg-1 with an average of (0.146+/-0.081) g.kg-1. SO42- was
the most abundant ionic component, followed by NH4+ and Ca2+. S was the most
abundant among all the elements, followed by Al, Ca, and Fe. The contents of OC
and EC fluctuated greatly, and the ratio of OC and EC produced by each boiler was
greater than one. In the range of the measured particle sizes, the mass
concentration of PM2.5 showed a singlet or bimodal distribution, and the peak
value appeared at 0.07-0.12 MUm and greater than 1 MUm in bimodal distribution.
The mass concentration of OC showed a bimodal or trimodal distribution, and the
peak value appeared at 0.04 MUm, 0.20-0.31 MUm, and greater than 1 MUm in
trimodal distribution. The efficiencies of the dust collection unit in removing
PM2.5, OC, and EC were 66%, 53%, and 23%, respectively.
PMID- 29964974
TI - [Emission Factors of Heavy Metals in Size-resolved Particles Emitted from
Residential Coal Combustion].
AB - Based on a dilution sampling system and domestic burning tests, size-segregated
particles emitted from burning of three kinds of honeycomb coals (in view of
flaming and smoldering burning conditions) and four kinds of raw coals, were
collected by cascade impactors (FA-3). The contents of V, Cr, Mn, Co, Ni, Cu, Zn,
As, Cd, Sb, and Pb were analyzed to get their emission factors (EFs) in different
particle size fractions. Results indicated that:1 Zn and Pb dominated the emitted
mass of heavy metals from chunk (53.16%-65.76%) and honeycomb (96.08% in 0.43
MUm) during the flaming combustion condition. However, the emission of Ni was
increased from 30.70% to 52.36% in the smoldering condition. Thus, combustion
condition may affect the composition of heavy metals in particle matters. 2 In
the flaming condition, both chunk and honeycomb emission factors of heavy metals
were concentrated under 1.1 MUm, while the larger sized particles in the range of
5.8-10 MUm were distributed. So, heavy metal components may shift to the larger
size of the particles at lower combustion temperatures. 3 Fine particle
matters(PM) was divided into three categories based on the size distribution of
11 kinds of heavy metal emission factors. The maximum emission values of As and V
fell under the PM size category of 5.8-10 MUm. The fourth cycle transition metal
elements, such as Cr, Mn, Cu, Ni, and Co, fell in the range of 1.1-2.1 MUm and
these elements represented similar emission characteristic features. Other
elements, such as Pb, Sb, Cd, and Zn, were concentrated in sizes less than 0.43
MUm. 4 The additive in the honeycomb during the process may import several kinds
of heavy metals and may change the combustion temperature, which remodels the
mechanism of heavy metal emission. Thus, honeycomb coal may emit different heavy
metals under different combustion conditions.The heavy metal emission mechanism
during honeycomb coal combustion needs further investigation and the emission
reduction effects (especially of heavy metals) needs to be re-estimated.
PMID- 29964975
TI - [Distribution of Oxalate in Atmospheric Aerosols and the Related Influencing
Factors in Qingdao, During Winter and Spring].
AB - A total of 119 total suspended particle (TSP) samples were collected in Qingdao
from December 2012 to April 2013. Concentrations of oxalate in TSP were measured
to investigate the distributional characteristics of oxalate and the related
influencing factors, in winter and spring. The concentrations of oxalate in
Qingdao aerosols were 31-370 ng.m-3 with an average of 104 ng.m-3 in winter, and
11-1926 ng.m-3 with an average of 400 ng.m-3 in spring, with a significant
difference between the concentrations in the two seasons. Different weather
conditions affected the distribution of oxalate in aerosols. The oxalate
concentration in TSP was the highest in the hazy days, followed by that in the
dusty days, while this concentration in foggy days was close to that in the clear
days, and the lowest concentration of oxalate appeared in the rainy days. Oxalate
in Qingdao aerosols exhibited a significant positive correlation with temperature
and solar radiation, suggesting that the secondary production of oxalic acid via
photochemical oxidation has an important contribution to the oxalate
concentrations in aerosols. The mechanisms of secondary formation of oxalate in
aerosols in winter and spring are possibly different, with the aqueous phase
oxidation process predominating in winter and the gas-phase oxidation-driven
process predominating in spring. The results of PMF source analysis also showed
that the secondary formation is the main source of oxalate in Qingdao aerosol,
and its contribution to oxalate production is nearly 45% in winter and 70% in
spring. The concentration of oxalate in spring aerosol was significantly higher
than that in winter aerosol, the main reason of which was that temperature and
solar radiation in spring were significantly higher than those in winter,
promoting the secondary formation of particulate oxalate.
PMID- 29964976
TI - [Concentrations and Solubility of Trace Elements in Atmospheric Precipitation in
Qingdao].
AB - Thirty-five atmospheric precipitation samples were collected at an urban site in
Qingdao from June 2016 to May 2017. The total and soluble concentrations of eight
trace elements in the samples were determined, and the variable characteristics
of the concentrations and solubility of trace elements, as well as the factors
affecting the solubility of trace elements in atmospheric precipitation, have
been discussed. Based on the overall data, the total concentrations of the trace
elements were found to be in the order Al > Fe > Zn > Mn > Ba > Pb > Sr > V, but
the soluble concentrations of the trace elements were in the order Zn > Al > Mn >
Fe > Ba > Sr > Pb > V. Solubility was about 5% for the crustal elements Al and
Fe, and the solubility of the elements affected by anthropogenic sources was
relatively higher, 10%-40% for Pb and Ba, 20%-60% for Mn and Sr, and nearly 55%
for Zn and V. The total and soluble concentrations of the trace elements were
higher in winter and spring than in summer and autumn, but element solubility in
spring was the highest. During continuous rainfall, the total concentrations of
trace elements in precipitation decreased appreciably, but the variation trend of
the solubility of trace elements was not consistent during the different rainfall
processes. The variation in pH was the main factor controlling the solubility of
trace elements in precipitation.
PMID- 29964977
TI - [Occurrence and Gas-particle Partitioning of Polycyclic Aromatic Hydrocarbons in
the Air of Liaodong Bay].
AB - The gas-and particle-phase polycyclic aromatic hydrocarbons (PAHs) were collected
from the air of Liaodong Bay in May and August to investigate their occurrence
and gas/particle distribution. The 24 PAHs were analyzed for gas-and particle
phase samples, and the concentrations of total gas-and particle-phase PAHs were
found to be 28.8 ng.m-3 and 24.0 ng.m-3, respectively. The concentrations of the
gas-phase PAHs were higher in August than in May, and the concentrations of the
particle-phase PAHs were higher in May than in August. The low molecular weight
PAHs were mainly distributed in the gas-phase, and the high molecular weight PAHs
were mainly distributed in the particle-phase; the medium molecular weight PAHs
were more easily affected by the environmental conditions than the low and high
molecular weight PAHs. The value of Kp increased with an increase in the
molecular weight. The slopes m for regressed lgKp-lgPL and lgKp-lgKOA plots were
0.35 and 0.37, deviated from -1 and+1 for the equilibrium states of gas/particle
partitioning. The equilibrium states of the lgKp-lgKOA, lgKp-lgPL, and soot-air
models were applied; the predicted results of the 5-ring PAHs fitted well with
the field measure results. The predicted results of the soot-air model were much
closer to the field measure results than the results of the lgKP-lgKOA and lgKP
lgPL models; compared to their heavier counterparts, the low and medium molecular
weight PAHs were influenced to a greater extent by soot.
PMID- 29964978
TI - [Analysis of Sources, Pollution Characteristics, and Human Exposure to
Atmospheric New Halogenated Flame Retardants in Selected Areas].
AB - Atmospheric gaseous and particle samples were collected using high-volume active
samplers in Guangzhou and Wuzhishan. Concentrations of all the eight selected new
halogenated flame retardants (NHFRs), including syn-DP, anti-DP, TBPH, PBEB, HBB,
TBE, TBB, and DBDPE, were measured. The mean ?NHFR concentration was
significantly higher in Guangzhou (335 pg.m-3) than in Wuzhishan (90.6 pg.m-3).
DBDPE was the most abundant component in Guangzhou, accounting for 66.9% of the
?NHFR concentration, while TBPH was the major component (65.8%) in Wuzhishan.
This indicates different pollution characteristics in Guangzhou and Wuzhishan. In
addition, ?NHFR concentration presented distinct seasonal variations only in
Guangzhou, which could result from the different sources of origin of NHFRs.
Principle component analysis showed that the atmospheric NHFRs in Guangzhou and
Wuzhishan could originate from different sources. In the light of the results of
wind frequency and HYSPLIT model analysis, NHFRs seem to originate mainly from
the emissions from surrounding areas, including from the inputs of e-waste
recycling, industrial activities, and re-volatilization of consumer goods in
Guangzhou, while NHFRs mainly seem to originate from the movement of air mass
over the Pearl River Delta and the seas in Wuzhishan. Meanwhile, several NHFRs
presented different loading patterns in Guangzhou and Wuzhishan, and the
emissions from different sources and commercial products could be the impactors.
With detection of high NHFR concentrations in the atmosphere of Guangzhou, the
long-time exposure of the surrounding residents (especially infants) is suspected
to cause potential health risk.
PMID- 29964979
TI - [Contamination Characterization and Human Exposure Levels to Polybrominated
Diphenyl Ethers in Indoor and Outdoor Air in Industrial Park of Suzhou City].
AB - Eight polybrominated diphenyl ether (PBDE) congeners in indoor and outdoor air
particles were collected using higher-volume active sampling techniques from
different functional areas, including an industrial workplace, office, domestic
area, and scenic area in an industrial zone, in Suzhou city, and the samples were
analyzed by GC-MS. The total concentration of PBDEs ranged from 9.22-64.15 pg.m-3
(average 20.93 pg.m-3), and 1.06-8.44 pg.m-3(average 5.11 pg.m-3)in indoor and
outdoor air, respectively. The results showed that the concentrations of PBDEs in
indoor PM10 was significantly higher than that in the outdoor PM10. The average
concentrations of PBDEs in the air of the different sampling areas were in the
order:industrial workplace As > Cd, and the risk levels ranged from 3.58E-06 to
1.21E-04 a-1; the risk values of Cr and As were higher than the maximum allowance
levels recommended by ICRP (5.0*10-5 a-1). Simultaneously, the risk levels of the
average non-carcinogenic health risks ranged from 3.53E-12 to 2.87E-09 a-1, and
the range was lower than the maximum allowance levels recommended by EPA.
Carcinogens, especially Cr and As, are the main causes of health risks in the
aquatic environment of the Liujiang river basin, and should be prioritized as the
main objects of aquatic environmental risk management in the Liujiang river
basin.
PMID- 29964985
TI - [Characteristics of Phosphorus Fractions and Phosphate Diffusion Fluxes of
Sediments in Cascade Reservoirs of the Huangbai River].
AB - The Huangbai river, with a large phosphorite deposit in the basin upstream, is
the drinking-water source of Yichang city, China, and water blooms often break
out in it in present times. To investigate the internal contamination load, the
distribution and vertical variation of sediment phosphorus and its fractions were
analyzed. Phosphorus flux across the sediment-water surface was preliminarily
analyzed in three reservoirs in the basin. The results showed that the
concentration of total phosphorus (TP) decreased from the upstream to the
downstream reservoirs of the basin, and the means of the TP were (8070.0+/
2251.4), (2681.2+/-1709.8), and (2656.6+/-1599.7) mg.kg-1, in the three
reservoirs, respectively. This shows that the basin is at a highly polluted
level. There were similar tendencies in the concentrations of dissolved oxygen
(DO) and chlorophyll a in the surface water. The order of the phosphorus
fractions was HCl-P > OP > NaOH-P in most sites. According to Fick's First Law,
the flux of PO43--P across the sediment-water surface was 0.0179-0.1825 mg.(m2.d)
1, and it decreased from the upstream to the downstream reservoirs. The flux was
positively related to HCl-P, OP, and TP in the high phosphorus concentration
basin.
PMID- 29964986
TI - [Occurrence and Ecological Risk Assessment of Typical Persistent Organic
Pollutants in Baiyangdian Lake].
AB - A comprehensive survey of the pollution characteristics of persistent organic
pollutants (POPs) in the surface water and surface sediment of Baiyangdian Lake
was carried out. The survey showed that:1 The concentrations of the polycyclic
aromatic hydrocarbons(PAHs), organic chlorine pesticides (OCPs), and
polybrominated diphenyl ethers (PBDEs) in the surface water of Baiyangdian Lake
were 71.32-228.27 ng.L-1, 2.62-6.13 ng.L-1, and 0-6.5 ng.L-1, respectively, and
those in the surface sediment were 163.20-861.43 ng.g-1, 2.25-6.07 ng.g-1, and
230.96-1224.13 pg.g-1, respectively. On comparison with historical data, the
concentrations of PAHs and OCPs in both the surface water and surface sediment
were found to be decreasing, while compared with the domestic and foreign lakes,
the concentration of PBDEs in the surface sediment was at a low level. 2 The main
source of PAHs, both in the surface water and surface sediment in Baiyangdian
Lake, originated from fuel discharge and combustion sources. HCHs compose the
main part of OCPs in both the surface water (93.76%) and surface sediment
(63.10%). In the surface water body, HCHs mainly originated from the degradation
of industrial HCHs; in some sites HCHs originated from atmospheric long-distance
transmission and the usage of Lindane, while DDTs originated from historical
residues. In surface sediment, HCHs mainly originated from the usage of new
Lindane, with little industrial HCHs, and DDTs mainly originated from historical
residues, while new DDTs may have been used in some sites. BDE-2 (65.80%)
composed the main part of PBEDs in the surface water, and it mainly originated
from atmospheric long-distance transmission and degradation of high brominated
diphenyl ethers; BDE-209 (63.82%) constituted the main part of PBDEs in the
surface sediment, and it mainly originated from the commercial Deca-BDEs.3
Ecological Risk Assessment show that there was no obvious ecological risks in
Baiyangdian Lake, but in some sites POPs may cause ecological risks; these sites
should be monitored more frequently.
PMID- 29964987
TI - [Simulating the Fate of Typical Organochlorine Pesticides in the Multimedia
Environment of the Pearl River Delta].
AB - A level IV multimedia fugacity model was established to simulate the fate of p,p'
DDT and gamma-HCH in special climatic conditions, such as in the high temperature
and humidity environment of the Pearl River Delta, China. The law of migration
and transformation of p,p'-DDT and gamma-HCH were approached by the IV multimedia
fugacity model, corrected for time and temperature change during 1952-2030. The
simulation results showed a better response of the variation of pollutant
concentrations to the changes in the pesticide application policy; the
concentrations of these two targets in air, water, soil, and sediment were found
continuing to increase with the growth of application rates, and decreased with
the prohibition in the use of pesticide. We predicted that concentrations will
decrease to 6.1*10-12, 3.2*10-9, 6.07*10-7, and 8.72*10-7 mol.m-3 for p,p'-DDT,
and to 3.37*10-11, 1.14*10-8, 1.21*10-6, and 4.18*10-7 mol.m-3 for gamma-HCH, in
air, water, soil, and sediment, respectively, by 2030. The output values of the
IV multimedia fugacity model corrected by designating temperature as a variable
parameter, was closer to the survey results than the simulation results obtained
by using the model with a constant temperature parameter. The results also showed
the pattern of organochlorine pesticides transformation in the whole
environmental media in the study area as follow:the pollutants transferred from
air to soil, air to water, soil to water, and from water to sediment, and were
lastly stored in the soil and sediment. The results of sensitivity analysis
indicated that the emission rate, degradation rate, temperature, and lgKow had
significant influences on the concentrations of p,p'-DDT and gamma-HCH in all the
above-mentioned environmental medias. Uncertainty analysis showed that changes in
the whole parameter sets had great impact on air concentrations. There were
seasonal variations in the distribution of organochlorine pesticide
concentrations, and temperature change had influence on its partition in the
environment.
PMID- 29964988
TI - [Mechanisms and Efficiencies of Removal of PPCPs by Pilot River Water Bypass
Treatment Process].
AB - The pharmaceuticals and personal care products (PPCPs) released into urban rivers
are triggering certain ecological risks. The current study investigated the
removal efficiencies of 30 frequently detected PPCPs by two river water bypass
treatment processes (CS-BAF-UF-Ozone and CS-MBR-Ozone), and investigated the
removal mechanism and eco-toxicological risk variation of target compounds via
section-removal investigation and risk quotient model, respectively. Results
indicated that both processes could efficiently remove the target PPCPs; the
removal rates of tetracyclines and caffeine were>90% in the biological sections,
while sulfonamides, fluoroquinolones, and other pharmaceuticals could only be
efficiently removed when the COD of the influent and the water temperature were
comparatively higher; the ozone process had particular effect on removing these
compounds. The cumulative removal rate of all PPCPs during the whole process was
higher than 92.5%. The total risk quotient (RQtot) of target PPCPs could be
efficiently reduced by the bypass treatment processes; the RQtot decreased from
12.6 in the influent river water to 0.2 in the ozone effluent, with a removal
rate of 98.4%.
PMID- 29964989
TI - [Chlorination of Naproxen: Removal, Transformation and Risk Assessment].
AB - The by-products produced during chlorination of pharmaceutically active compounds
(PhACs) have created widespread public concern. Chlorination of a typical PhAC,
naproxen (NAP), was studied. NAP chlorination parameters, intermediates
identification, chlorination mechanism, and risk assessment during chlorination
process have also been discussed. The results showed that NAP chlorination could
fit well with the fist-order kinetics. The rate of removal and rate constants of
NAP chlorination decreased with increasing initial NAP concentration and ammonium
dosage, while these values increased with increasing initial free chlorine
concentration. Acidic condition of the solution could significantly promote NAP
chlorination. Five intermediates were identified by HPLC-MS/MS, and the mechanism
of NAP chlorination was also put forward. Vibrio fischeri toxicity analysis and
ESCOAR prediction indicated that higher toxicity intermediates were produced
during NAP chlorination, which pose a potential threat to drinking water safety.
PMID- 29964990
TI - [Removing Typical Odorants in Drinking Water by Vacuum Ultraviolet Combined with
Chlorine].
AB - For the effective removal of two typical odorants found in drinking water, 2
methylisoborneol (2-MIB) and geosmin (GSM), which cannot be effectively removed
by the conventional water treatment processes, the advanced oxidation process of
vacuum ultraviolet combined with chlorine (VUV/chlorine) was studied. The
efficiency of this technology in the removal of these typical odorants was
investigated; the effects of ultraviolet intensity, chlorine concentration, pH,
bicarbonate concentration, and humic acid concentration on the degradation of
these typical odorants were examined, and the role of hydroxyl radicals (.OH) in
the degradation of these typical odorants was analyzed. The purge and trap method
coupled with gas chromatography and mass spectrometry (GC/MS) was used to
determine the concentrations of the typical odorants. The results showed that the
VUV/chlorine technology removed typical odorants effectively, and the removal
rates of 2-MIB and GSM increased by 15% and 8%, respectively, in 30 minutes,
compared with that by the UV/chlorine technology. With the increase in chlorine
concentration and ultraviolet intensity, the degradation rates of the typical
odorants was accelerated. The removal of the typical odorants was obvious under
weak acid condition, and the removal rates of 2-MIB and GSM reached 95% and 96%,
respectively, in 10 minutes under the condition of pH 5. Bicarbonate and humic
acid competed with free radicals in the reaction system to inhibit the
degradation of the typical odorants. The removal rates of 2-MIB and GSM decreased
appreciably by 40% and 31%, respectively, when 1 mmol.L-1tert-butanol was added
to the reaction mixture, which indicated that hydroxyl radicals (.OH) played a
major role in the removal of these typical odorants.
PMID- 29964991
TI - [Degradation of Triclosan by Heat Activated Persulfate Oxidation].
AB - Sulfate radical (SO4.-)-based advanced oxidation technologies (SR-AOPs) are
widely used for remediation of contaminated groundwater and soils. This study
investigated the reaction kinetics, products, and transformation pathways of
triclosan, a widely used antimicrobial agent, during its degradation by heat
activated persulfate oxidation. Experimental results revealed that increasing
temperature or initial persulfate concentration significantly enhanced the
degradation of triclosan. The reaction could be fitted in the pseudo-first-order
kinetic model and the activation energy (Ea) was determined to be 142 kJ.mol-1.
The presence of humic acid markedly inhibited triclosan degradation, whereas
chloride (Cl-) showed a more complicated effect. Triclosan degradation was
slightly accelerated in the presence of 5 MUmol.L-1 Cl-, however, a higher
concentration of Cl- (e.g., 10 MUmol.L-1) showed an inhibitory effect. Using
liquid chromatography-mass spectrometry, a total of six transformation products,
including 4-chlorocatechol, 2,4-dichlorophenol, and 2-chloro-5-(2,4-dichloro-6
hydroxyphenoxy)-1,4-benzoquinone, were identified. Accordingly, the cleavage of
the ether bond and hydroxylation of the phenol ring were proposed as the
principal pathways of triclosan degradation upon reaction with SO4.-. The
findings of this study can be used to evaluate the feasibility of decontamination
of triclosan by SR-AOPs.
PMID- 29964992
TI - [Adsorption of Tetracycline on Simulated Suspended Particles in Water].
AB - The mechanism of adsorption of a typical antibiotic (tetracycline, TC) on
particles in the aquatic environment and the parameters affecting adsorption were
investigated. Experiments were conducted to elucidate the effects of pH and
various cation species with different concentrations. The results show that the
adsorption of TC on particles is rapid during the first four hours in the mixing
stage. The adsorption process becomes slow after the first four hours. The
adsorption of TC on particles can be described well by a Langmuir equation. The
maximum adsorption of TC on particles occurs at pH 4.5, however it is reduced by
strongly acidic (pH<4) or alkaline (pH>9) conditions. Moreover, the adsorption
process is also inhibited by various cations (e.g. Na+ and Ca2+) in the range of
0.0001-0.1 mol.L-1 ionic concentrations. A special finding concerns Al3+ ions; at
a low concentration of these ions (0-0.0001 mol.L-1) the adsorption of TC on
particles improves, whereas at increased concentrations the adsorption is
weakened. In summary, an effective removal of the particles is critical to
control TC pollution in natural waters because of the rapid adsorption of TC on
particles.
PMID- 29964993
TI - [Characteristics and Performance of Embedded ANAMMOX Bacteria in Treating Saline
Wastewater].
AB - In order to improve the mechanical stability of the material, the embedded raw
material combination was studied in the experiment, and seawater was added to
optimize the performance of the material. The results indicated that the optimal
material ratio was polyvinyl alcohol (PVA 125 g.L-1)-alginate sodium (SA 20 g.L
1)-activated carbon (40 g.L-1). The curing time was 18 h. After adding seawater,
the beads were found to have larger pore sizes inside, and the pores were
distributed unevenly because of the Hofmeister effect. At the same time, the
mechanical stability and biological capacity were found to be significantly
higher than those of the fresh water group. The Raman spectra analysis showed
that the addition of seawater made the-OH on PVA have greater crosslinking
reactions with the crosslinker. The activated sludge was used to treat wastewater
containing sea water, and after an operation of 21 d, the removal rate of NH4+-N
was about 90%, and the stoichiometric ratio of ?NH4+-N:?NO2--N:?NO3--N was stable
at 1:(1.04+/-0.1):(0.17+/-0.02). From the 21st day to the 46th day, the reactor
was run in a steady state. When the nitrogen load rate doubled, the ammonia
nitrogen removal rate and stoichiometry had little variations. The total nitrogen
removal rate was about 85%, and the total nitrogen removal load rate was 0.2
kg.(m3.d)-1.
PMID- 29964994
TI - [Enhanced Nitrogen Removal of ANAMMOX Treating Saline Wastewater With Betaine
Addition].
AB - High salt content could result in the inhibition of microbes and affect
biological treatment processes. At present, an important research topic is how to
improve the efficiency of biological treatments. The anaerobic ammonia oxidation
(ANAMMOX) process was used to treat high saline wastewater. Nitrogen removal
performance with betaine was studied by analyzing the ANAMMOX activity, and
ammonia nitrogen and nitrate nitrogen removal. The results showed that:1 It has
obvious improvement when betaine concentration was 0.1-0.4 mmol.L-1. It
alleviated the salt stress on bacteria growth inhibition of ANAMMOX, and also
promoted the growth of denitrifying bacteria. When betaine concentration was 0.4
0.5 mmol.L-1, denitrifying bacteria was found to have grown greatly. When betaine
concentration was greater than 0.5 mmol.L-1, it was unable to alleviate the salt
stress inhibiting denitrification efficiency. As a result, betaine concentration
of 0.8 mmol.L-1 completely inhibited bacteria. 2 When concentration of betaine
was 0.3 mmol.L-1, the optimal nitrogen removal efficiency was achieved. NH4+-N
and NO2--N increased by 16% and 32%, respectively. Nitrogen removal rate (NRR)
increased by 26.8%. 3 At the end of the recovery experiment, with the decreasing
concentrations of betaine, NH4+-N was 50.6%, NO2--N was 63.7%, and NRR was 0.65
kg.(m3.d)-1, so the nitrogen removal efficiency underwent fast recovery.
PMID- 29964995
TI - [Pilot-scale Experiment on Enrichment of Nitrifying Activated Sludge and Its
Application in Enhancing a Wastewater Biological Treatment System Against Ammonia
Shocking Loads].
AB - Nitrifying activated sludge (NAS) was enriched in a membrane bioreactor (MBR)
with pre-treated municipal wastewater and additional ammonium sulfate as the
culture medium. The influences of temperature, dissolved oxygen (DO), ammonia
nitrogen volumetric load, free ammonia (FA), and free nitrite (FNA) on the
enrichment of NAS were investigated, the cost of the process was evaluated, and
then NAS's application in enhancing a wastewater biological treatment system
against ammonia shocking loads was attempted. The results showed that after 182
days of cultivation in an MBR, NAS had a nitrification activity of 98.41 mg.(L.h)
1, which was 30-times higher than that of the seeding sludge. The yield of NAS
was 14.96 mg.(L.d)-1, costing 3.52 Yuan for 1 kg. Temperature was found to be a
key factor affecting the sludge nitrification activity. The sludge nitrification
activity was decreased to 1/3 of the maximum value at temperatures below 15.0C,
while lowering the ammonium volumetric load retarded the decrease in the sludge
nitrification activity to some extent. In addition, dissolved oxygen deficiency
resulted in nitrite accumulation, and thereby slowed down the NAS enrichment
rate. The enriched NAS was then applied to a wastewater biological treatment
pilot equipment, which had just been exposed to an ammonium shocking load. The
removal rate of ammonia nitrogen in the biological system increased from 29.4% to
88.4% after 2.0% of NAS was inoculated. The enhanced biological system retained
ammonia removal rates of as high as 99.0%, even as the temperature dropped to
13.3C+/-1.6C afterwards. The above pilot-experiment results suggested that
enriched nitrifying sludge is suitable for quickly increasing the start-up or
recovery rates of the nitrifying function in a biological system.
PMID- 29964996
TI - [Effect of Step Feed on Denitrifying Phosphorus and Nitrate Removal in a
Modification of the Two Sludge A2/O-BAF System].
AB - A modification of the two sludge A2/O-BAF system was used to treat low C/N real
domestic sewage. In order to improve the utilization of the carbon source, the
effects of two step feeds (pre-anoxic zone and anoxic zone) on denitrifying
phosphorus and nitrate removal were studied. According to the formula of material
balance for COD, the utilization of carbon source was analyzed and evaluated
under different ratios of step feed, simultaneously. The results showed that when
the ratio of step feed was 7:3 and the influent concentrations of COD, NH4+-N,
TN, and TP were 174.99, 58.19, 59.10, and 5.15 mg.L-1, respectively, their
effluent concentrations were 29.48, 4.07, 14.10, and 0.40 mg.L-1, and the removal
rates were 82.12%, 92.76%, 75.45%, and 91.20%, respectively. It was found that
when the ratio of the denitrifying phosphorus accumulation organisms to the
phosphorus accumulation organisms(DPAOs/PAOs) was 98.81%, the efficiencies of
denitrifying phosphorus and nitrate removal were optimum. By optimizing step
feed, the carbon source was utilized effectively, and the efficiencies of
nitrogen and phosphorus removal were improved simultaneously. The theoretical
basis has thus been provided for the modification of the two sludge A2/O-BAF
system to treat low C/N waste water.
PMID- 29964997
TI - [Achieving Partial Nitritation in a Continuous-flow Aerobic Granular Sludge
Reactor at Different Temperatures Through Ratio Control].
AB - Mature aerobic granular sludge (AGS) was inoculated in a continuous-flow reactor
to treat low ammonia sewage, and the feasibility of achieving partial nitritation
in a continuous-flow aerobic sludge system and the demand for R value (the ratio
of dissolved oxygen and ammonia nitrogen) when partial nitritation is achieved at
different temperatures (30, 20, and 10C) were investigated. The control strategy
was designed to maintain a constant ratio between dissolved oxygen (DO) and
ammonia nitrogen (NH4+-N). The results revealed that stable nitritation in a
continuous-flow aerobic sludge reactor could be achieved via ratio control, and
the value of R were 0.50 (+/-0.05), 0.35 (+/-0.03), and 0.20 (+/-0.02) at the
temperatures 30, 20, and 10C, respectively, from which it can be concluded that
stronger oxygen-limiting conditions were required when the temperature was lower.
The experiment of fluorescence in situ hybridization (FISH) revealed that ammonia
oxidizing bacteria (AOB) have a certain concentration, and the relative number of
nitrite oxidizing bacteria (NOB) gradually reduced through the ratio control
strategy. Based on the ratio control strategy and the characteristics of
wastewater quality, full nitritation of high ammonia wastewater may be allowed;
however, for low ammonia wastewater, only partial nitritation is recommended.
PMID- 29964998
TI - [Mechanism of Action of Activated Sludge Properties in Nitrogen Removal by
Endogenous Denitrification Through an Intelligent Aeration-controlled A/O
Process].
AB - In order to evaluate the mechanism of action of activated sludge properties in
nitrogen removal by endogenous denitrification (henceforth EDNR), a new kind of
automatic oxygen supply device(AOSD), was applied to the A/O process. The
domestication effect of the aeration mode on the activated sludge properties and
microbial communities was investigated under the intelligent aeration-controlled
A/O process (I-A/O)and the continuous aeration A/O process (C-A/O). The results
demonstrated that the effluent NH4+-N and NO2--N components showed obvious
accumulation efficiencies and activated sludge generated conspicuous limited
bulking in the I-A/O process. Domesticated sludge in the I-A/O process was able
to enrich more SCOD to transfer into the polymeric substances as Gly, under a
rich exogenous carbon supply state, and stimulated nitrogen removal by endogenous
denitrifying under a scarce exogenous carbon supply state. The EDNR rate went up
to 0.83 mg.(L.h)-1 in the I-A/O process, which was more than that achieved by the
C-A/O process. The microbial communities in the two processes were evaluated by
the Illumina HiSeq high-throughput sequencing technology. The results showed that
there was no obvious difference in the sludge microbial community diversity
between the two processes, but the Candidate division TM7 proliferated in the I
A/O process, and become the abundant taxa to prompt limited filamentous sludge
bulking and Gly storage capability enhancement. The oxygen supply mode of AOSD
made the activated sludge properties and microbial communities to be screened
selectively in the new environment, aerobic heterotrophic bacterial activity to
decline, and endogenous denitrifying action to strengthen, which made the I-A/O
process implement a kind of dynamic balanced state that limited the DO demand.
PMID- 29964999
TI - [Effect of Temperature on the Performance and Microbial Community Structure in an
Integrated Anaerobic Fluidized-bed Membrane Bioreactor Treating Benzothiazole
Wastewater].
AB - An integrated anaerobic fluidized-bed membrane bioreactor (IAFMBR) was applied to
treat synthetic high-strength benzothiazole wastewater. This study investigated
the effect of temperature on the performance, membrane fouling and microbial
community structure of IAFMBR. The results showed that decreasing temperature had
an adverse effect on the performance and the cycle of membrane fouling. When
temperature declined from 35C to 15C, the COD efficiency dropped 7.4%,
benzothiazole removal efficiency dropped 49.2%, the accumulation of total VFAs
increased 225.66 mg.L-1, and methane yield (in CH4/CODremoved) dropped 0.118
m3.kg-1. The membrane fouling cycle shortened from 5.2 d to 2.5 d. For cake
layer, the concentration of soluble microbial product (SMP) increased from 42.47
mg.L-1 to 70.62 mg.L-1, and the extracellular polymeric substance (EPS) content
(in VSS) increased from 46.30 mg.g-1 to 82.22 mg.g-1 when the TMP was 15 kPa. For
mixed liquor, the concentration of SMP increased from 36.46 mg.L-1 to 69.35 mg.L
1 and the EPS content increased from 47.47 mg.g-1 to 81.63 mg.g-1. Protein was
the main component of EPS and SMP, and occurred in proportion of 80%.The
microbial community structure showed that the dominant phyla were Firmicutes and
Chloroflexi, which accounted for 42.6%-61.0% of the total relative abundance. The
genera Clostridium (13.7%), Levilinea (15.2%), and Lactococus (17.9%) dominated
with decreasing temperatures. The dominant methanogen was Methanosaeta.
PMID- 29965000
TI - [Removal of Antibiotics During In-situ Sludge Ozone-reduction Process].
AB - Two sequencing batch reactors were established at bench-scale, with one used as
an in-situ sludge ozone-reduction system and the other as a control system. Both
systems were continuously operated for 90 days to comparatively investigate the
elimination of nine typical antibiotics (i.e., tetracycline, oxytetracycline,
doxytetracycline, norfloxacin, ofloxacin, ciprofloxacin, lomefloxacin,
enrofloxacin, and azithromycin) during the in-situ sludge ozone-reduction
process. Results indicated that the presence of target antibiotics in the
influent (100 MUg.L-1 each) had an insignificant influence on the removal of COD,
total nitrogen, ammonia, and total phosphorus by the activated sludge. The
antibiotic concentrations in the effluent of the reduction system remained fairly
stable over the entire operation period, and were similar to those in the
effluent of the control system; however, the antibiotic concentrations in the
sludge of the reduction system were obviously lower than those in the control
system sludge. Mass balance calculations revealed that the input and output of
target antibiotics gradually approached balance in both the systems. Ozone
degradation and excess sludge discharge were the main pathways for target
antibiotic removal in the reduction and the control systems, respectively. The
influent antibiotics could be degraded by 83% in the sludge ozonation module of
the reduction system, while 82% of the influent antibiotics were discharged with
excess sludge in the control system. Therefore, the in-situ sludge ozone
reduction process could greatly reduce the release of antibiotics from the
activated sludge system, which is of great importance in practice.
PMID- 29965001
TI - [Effect of Zero Valent Iron on the Horizontal Gene Transfer of Tetracycline
Resistance Genes During Anaerobic Sludge Digestion Process].
AB - The problem of bacterial resistance has become an important issue in the area of
global ecological safety and human health. Waste sludge is an important reservoir
and discharge source for antibiotic resistance genes (ARGs). In this study, the
quantities of seven tetracycline resistance genes (TC-ARGs), including tetA,
tetC, tetG, tetM, tetO, tetW, and tetX, as well as those of class 1 integron
(intI1) genes, during anaerobic sludge digestion process were comprehensively
quantified by quantitative PCR (qPCR). The effects of different doses of zero
valent iron (Fe0) on the decrease and increase in the quantities of TC-ARGs and
intI1 genes were investigated. The influence of plasmid conjugation on the
horizontal gene transfer (HGT) of the target TC-ARGs was preliminarily analyzed.
The correlations between the quantities of TC-ARGs and intI1 gene have been
discussed. The results showed that the quantities of TC-ARGs and intI1 genes
decreased in different degrees during anaerobic sludge digestion, and the
abundance of tetX gene was reduced by 2.4 orders of magnitude. When Fe0 was
added, no significant reduction in the quantities of TC-ARGs and intI1 genes was
observed. However, as the addition of Fe0 increased, the quantities of TC-ARGs
and intI1 genes increased correspondingly, as compared to those in the control
group. The results obtained from the quantities of TC-ARGs carried by plasmid DNA
showed that plasmid conjugation probably promoted the HGT of TC-ARGs. A positive
significant correlation was found between the quantities of tetG and intI1 genes,
indicating that intI1 might play an important role in the evolution of tetG
during sludge anaerobic digestion process.
PMID- 29965002
TI - [Effects of Environmental Factors on the Synergy of Functional Bacteria in
Completely Autotrophic Granular Sludge].
AB - To obtain experimental evidences for optimizing a completely autotrophic nitrogen
removal process based on granules, the effects of dissolved oxygen (DO)
concentration, temperature (t), initial ammonium (NH4+-N) concentration, and
solution pH conditions on the synergy between the aerobic and anaerobic ammonium
oxidizing bacteria (AOB and AMX) were investigated using a single factor batch
experiment, while the analysis of the microbial community structure within them
was conducted using MiSeq high-throughput pyrosequencing. Results revealed that
AOB (genus Nitrosomonas) and AMX (genus Candidatus Kuenenia) dominated in the
granules, representing relative abundances of 32.9% and 9.8%, respectively. For
the granules, the highest specific nitrogen removal rate of q(TN)=(17.7+/-1.0)
mg.(g.h)-1 was obtained at a DO concentration of 2 mg.L-1, while the initial NH4+
N concentration was set at 100 mg.L-1. And a lower DO level resulted in partial
nitritation became the rate-limiting step of process, otherwise, it would be the
ANAMMOX reaction instead. According to the free energy of the reactions, the
activity of AMX was more sensitive to low temperature than that of AOB. When the
reaction temperature was lower than 30C, nitrite accumulation could be observed
in bulk liquid, with the significant decrease of q(TN) for the granules. Under
the same oxygen supply conditions, an initial NH4+-N concentration lower than 100
mg.L-1 could inhibit the activity of AMX partly. However, with an initial NH4+-N
concentration over 150 mg.L-1, either oxygen-limiting or high free ammonia
concentration could lead to the dramatic decrease of q(TN). In addition, the
effective synergy of the two types of ammonium oxidizers in granules was always
achieved at solution pH in the range of 7.0-8.5.
PMID- 29965003
TI - [Microbiological Characteristics of a Post Solid-Phase Denitrification Biofilter
Process].
AB - To solve the problems of high energy consumption, complex process, and low
nitrogen removal efficiency of the currently available low carbon source
wastewater treatment processes, a novel coagulation sedimentation/post solid
phase denitrification biofilter process was proposed. Domestic wastewater with
low carbon to nitrogen ratio was treated. The changes in the microbial community
structure along the biofilters were studied and the functional bacteria were
identified using the polymerase chain reaction denaturing gradient gel
electrophoresis (PCR-DGGE). The results showed that the microbial diversity and
richness of the microorganisms increased from the bottom to the top along the
nitrification filter, while in the denitrification filter, there parameters
increased firstly and then decreased from the bottom to the top along the
cylinder. A bigger population of nitrifying and denitrifying bacteria was
observed at the top and the middle of the nitrification and denitrification
biofilter, respectively. Moreover, Nitrosomonas sp. Nm47 and Candidatus
Nitrospira defluvii were the predominant nitrifying bacteria in the nitrification
biofilter, and Myxobacteria and Rubrivivas gelatinosus were the predominant
denitrifying bacteria in the solid-phase denitrification biofilter.
PMID- 29965004
TI - [Aerobic Denitrification and Microbial Community Shift in SBR Bioaugmented with
Strains YH01 and YH02].
AB - The enhanced aerobic denitrification capability of the mixed strains YH01+YH02 in
utilizing potassium nitrate, and the dynamic changes in the microbial community
component during the period of operation, were evaluated. The microbial community
in different stages of the SBR was analyzed by using high-throughput sequencing
technology after inoculation with YH01+YH02. The results showed that the NO3--N,
TN, and COD removal efficiencies increased by 12.1%, 9.2%, and 9.4%,
respectively. The relative abundances of the microbes in the microbial community
increased at the genus level, and the diversity in the microbial community
decreased after enhancement. Principal component analysis and UPGMA analysis
revealed that the period of SBR operation was roughly divined into four phases.
The relative abundances of Delftia and Acidovorax increased during the period of
operation, and YH01+YH02 exhibited excellent compatibility with the SBR ecosystem
and played an important part in aerobic denitrification.
PMID- 29965005
TI - [Performance, Sludge Characteristics, and the Microbial Community Dynamics of
Bulking Sludge Under Different Nitrogen and Phosphorus Imbalances].
AB - In this paper, the performance, characteristics of the bulking sludge, and the
variations in the microbial community (including the bulking bacteria) under
different nitrogen and phosphorus imbalances were compared, using high-throughput
sequencing (16S rRNA) and the high performance liquid chromatography (HPLC)
technology. The results showed that after seeding bulking sludge in the A/O
process and operating for a period of time, the sludge settleability of the
nitrogen limitation alone reactor (RN) could recover to normal[sludge volume
index (SVI)<150 mL.g-1], while the SVI of the phosphorus limitation alone reactor
(RP) improved slightly; the control reactor (R0, C/N/P=100/5/1) exhibited the
highest SVI index (SVI=1496 mL.g-1), followed by the reactor of simultaneous
nitrogen and phosphorus limitations (RNP). Under normal nutritional conditions,
Pearson correlation analysis showed a significant negative correlation between
the lipopolysaccharide (LPS) relative content (LPS/MLVSS) and the settleability
of bulking sludge (r=-0.625, P<0.05), while under nutrient limitation conditions,
LPS showed high accuracy in reflecting the biomass of the activated sludge.
Thiothrix was the dominant bulking bacteria in all the reactors. PCoA analysis
showed that the migration of the community in the reactors experienced nitrogen
limitation (RNP, RN) changes greatly during the stages II and III, while RDA
analysis showed that the correlation of Thiothrix with the settling performance
and oxygen consumption rate was significant.
PMID- 29965006
TI - [Degradation Characteristics and Metabolic Pathway of a Pyrene-Degrading
Pseudomonas aeruginosa Strain].
AB - Polycyclic aromatic hydrocarbons (PAHs) pose a potential threat to ecosystems due
to their mutagenic, carcinogenic, and teratogenic effects. Microbial degradation
has been suggested as the best way to remove PAHs from contaminated environments.
Screening of bacterial strains capable of efficiently degrading PAHs is the key
to the bio-remediation technique. With the method of enrichment culture, the
bacterial strain LX2, which can use pyrene as the sole carbon source, was
isolated from sludge contaminated with PAHs. The strain was identified as
Pseudomonas aeruginosa (Pseudomonas sp. LX2) according to the results of the
analyses of its morphology, physiology, and phylogeny of its 16S rDNA sequence.
The degradation rate of pyrene by Pseudomonas sp. LX2 was 32.1% after 21 days of
cultivation at an initial pyrene concentration of 50 mg.L-1. Pyrene, 4,5-dihydro
, 2'-Hydroxypropiophenone, Phenol, and Protocatechuate were identified as the
major metabolites by GC/MS analysis. Based on the identified metabolites, it was
concluded that pyrene was degraded via two different routes by Pseudomonas
aeruginosa, namely the 'naphthalene' and the 'phthalic acid' routes.
PMID- 29965007
TI - [Driving Factors of the Dynamics of Microbial Community in a Dam of Copper Mine
Tailings].
AB - The relative importance of the deterministic versus stochastic processes
underlying community dynamics has long been a central theme in community ecology,
and is intensively debated in the field. Microbial communities play key roles in
nutrient cycling and the flow of energy in ecosystems. The research on the
structural dynamics of microbial community will provide data and theoretical
support for understanding the assembly mechanisms of community, and for
predicting the dynamics of microbial community under environmental stress. In
this study, the Illumina MiSeq method was applied to investigate the structural
dynamics of bacterial and fungal community in a dam of Shibahe mine tailings at
different restoration stages (1-45 years). The results indicated that the soil
physicochemical properties in the dam of mine tailings formed an ecological
gradient, and the plant community showed succession along the restoration time.
The diversity of plant communities was significantly correlated with soil
nutrient contents but not with soil heavy metal contents. The structure of the
microbial communities showed significant differences at different restoration
stages of the dam land, in which Proteobacteria, Actinobacteria, Firmicutes, and
Acidobacteria were the dominant bacterial phyla, and Ascomycota, Basidiomycota,
and Zygomycota were the dominant fungal phyla. The assembly of the microbial
community was shaped mainly by the soil nutrients and soil heavy metal contents,
but plant diversity had no significant effect on the microbial community
structure. It was suggested that edaphic factors drive the dynamics of microbial
communities under the stress conditions of pH and heavy metals on small, local
scales.
PMID- 29965008
TI - [Effects of Reclamation on Soil Nutrients and Microbial Activities in the Huixian
Karst Wetland in Guilin].
AB - To investigate the effect of reclamation on soil quality in the Huixian Karst
Wetland, samples from different soil levels were collected from marsh wetland,
reclaimed paddy field, and reclaimed dry farmland, for analyzing soil nutrient
(carbon, nitrogen, phosphorous, and potassium) contents, microbial biomass
carbon/nitrogen (MBC/MBN), and microbial activity indicators[i.e. basal
respiration (BR), potential respiration (PR), microbial quotient (qMB), and
metabolic quotient (qCO2)]. The correlations between the soil nutrient contents
and soil microbial activity indictors were examined. The results showed
that:1Artificial reclamation led to the trend of slight acidity in the soil and a
marked loss in soil nutrients, while, the pH value, soil water content (SWC), and
the contents of soil organic carbon (SOC), total nitrogen (TN), available
nitrogen (AN), total phosphorus (TP), available phosphorus (AP), total potassium
(TK), and available potassium (AK) decreased with reclamation. 2Among all the
microbes, bacteria were the most numerous, followed by actinomycetes, and fungi
were the least numerous. The microbial quantity decreased with the increase in
the soil depth on the whole. The proportion of bacteria and actinomycetes were
much higher in the paddy field, and that of fungi was the highest in the dry
farmland. 3 In total, protease, sucrase, urease, catalase, and polyphenol oxidase
activities decreased with the increasing of soil depths. Soil reclamation reduced
the soil enzyme activities. 4qCO2 decreased after an initial increase in the
marsh wetland, while it rose gradually in the reclaimed paddy field and reclaimed
dry farmland. The contents of MBC, MBN, BR, PR, and qMB were the highest in the
marsh wetland, followed by those in the reclaimed paddy field, with the lowest
contents occurring in the reclaimed dry farmland. The trend of qCO2 contents in
the 0-10 cm and 10-20 cm soil layers followed the order of marsh wetland > paddy
field > dry farmland, but in the 20-30 cm and 30-40 cm soil layers, it showed the
order dry farmland > paddy field > marsh wetland. The continuation of reclamation
resulted in the decrease in soil microbial activity, and soil quality as well,
especially in the dry farmland. Meanwhile, we should reduce the areas of paddy
fields and dry farmlands under reclamation during the process of wetland
ecological restoration in future. Conversion of farmlands to wetlands or lakes,
to improve and increase the size of wetland ecosystems of nearby lands, should be
done gradually.
PMID- 29965009
TI - [Effects of the Farmland-to-Forest/Grassland Conversion Program on the Soil
Bacterial Community in the Loess Hilly Region].
AB - This study investigated the effects of the program aimed at converting farmland
into forest or grassland on the soil bacterial diversity in the Loess Hilly
region. Corn land was selected as the experimental control, and Caragana
intermedia land and Stipa bungeana land were selected as the experimental lands.
Soil from three different land use types were selected as subjects. The soil
bacterial communities were analyzed using a high throughput sequencing technique
(MiSeq). The sequence region was 16S rRNA V3-V4 variable region. The alpha
diversity, community composition, and relative abundances of the soil bacterial
groups were analyzed, in order to explore the effects of soil physical and
chemical properties on the bacterial community structure. The results showed that
the structure and diversity of the microbial communities differed under the
different land use types. At the phylum level, the dominant phyla were
Proteobacteria, Actinobacteria, Acidobacteria, Chloroflexi, Gemmatimonadetes, and
Firmicutes. At the class level, alpha-Proteobacteria, Actinobacteria,
Acidobacteria, beta-Proteobacteria, Thermoleophilia, Gemmatimonadetes, Bacilli,
and delta-Proteobacteria were predominant. Compared to the corn land,
Proteobacteria and Actinobacteria were the dominant bacteria in the Caragana
intermedia land, while Actinobacteria and Acidobacteria were the dominant
bacteria in the Stipa bungeana land. Soil bacterial diversity was the highest in
the shrub land. RDA analysis revealed that soil organic matters and total
nitrogen were the most influential environmental factors. It was shown thus that
the program of converting farmland into forest or grassland has significantly
improved the soil fertility and environmental conditions, and the composition of
the soil bacterial community has also been appreciably changed.
PMID- 29965010
TI - [Insight into the Mechanism of Feammox in the Surface Soils of a Riparian Zone].
AB - Anaerobic ammonium oxidation coupled to iron (III) reduction (termed Feammox) is
a recently discovered pathway of nitrogen cycling. However, little is known about
the pathways of N transformation via the Feammox process in riparian zones. In
this study, evidence of Feammox in the riparian zone soil layers (0-20 cm) was
demonstrated using the isotope tracing technique and a high-throughput sequencing
technology. The results showed that Feammox occurred in the riparian zones in
four different soil layers (A:0-5 cm, B:5-10 cm, C:10-15 cm, D:15-20 cm) and the
Feammox rates ranged from 0.25 mg.(kg.d)-1 to 0.29 mg.(kg.d)-1. In the B soil
sample, the Feammox rate was significantly higher than in the other soil samples
(P<0.05). In addition, iron reducing bacteria played an essential role in the
Feammox process, and Anaeromyxobacter and Geobacter were detected in all the soil
samples. In the B soil sample, the abundance of iron reducing bacteria was
significantly higher than in the other soil samples (P<0.05). Overall, the co
occurrence of ammonium oxidation and iron reduction suggest that Feammox can play
an essential role in the pathway of nitrogen removal in riparian zones.
PMID- 29965011
TI - [Soil Degradation-Associated Microbial Community Structure Changes in an Alpine
Meadow Under Tibetan Pig Herding].
AB - Anthropic activities lead to a high risk of peatland degradation in the alpine
regions. Along with the declined plant productivity and the impaired functioning
of the soil carbon sink, the diversity and structure of soil microbial
communities are also affected in a degraded peatland ecosystem. Tibetan pig
herding is a unique peatland management strategy, which can significantly affect
the peatland ecosystem, but it has been rarely studied. The changes in the
microbial community structure and its responses to disturbances were studied
using a 16S rRNA high throughput sequencing technique in an alpine meadow
peatland under Tibetan pig herding disturbance and under control (without Tibetan
pig herding) in the Northwestern Yunnan province. The results showed that Tibetan
pig herding significantly reduced the alpha diversity of soil microbes, and the
soil microbial community structures were significantly changed by pig herding.
The soil microbial communities in the peatland soils were dominated by
Proteobacteria, Acidobacteria, and Chloroflexi. Compared with those at the phylum
level, the changes at the genus level under pig disturbance were more obvious. It
was seen that the relative abundances of Sphingomonas and Hymenobacter
significantly increased, while the abundances of Nitrospira and Rhodoplanes
significantly decreased under pig herding. Venn diagram analysis revealed that
there were 71 and 136 core OTUs in the soil under pig herding and in the control
group soil, respectively. Burkholderiales, Pseudomonadales, and Sphingomonadales
were the main taxa exclusively found under Tibetan pig herding, and could serve
as indicators of soil disturbance. CCA ordination further showed that the
distribution of Nitrospira and Rhodoplanes were mainly controlled by soil
moisture, available phosphorus, and organic matter contents. Our findings provide
an insight into the linkages between the soil microbial communities and the
degradation of peatlands in alpine regions.
PMID- 29965012
TI - [Characteristics of Iron Plaque and Its Heavy Metal Enrichment in Typical
Mangrove Plants in Shenzhen Bay, China].
AB - Based on the five typical mangrove species in the mangrove wetland of Shenzhen
Bay, the contents and distributional characteristics of iron plaques (Fe) and the
Mn, Pb, Zn, Cu, As, Cr, Cd, Ni, Co, and Sb enrichment of the iron plaques on
mangrove plant roots were investigated. The results show that:1 There is a
significant difference in the contents of iron plaques among the five mangrove
species, and the contents in the species follow the order:Acanthus ilicifolius >
Aeagiceras corniculatum > Bruguiera gymnorrhiza > Kandelia obovate > Heritiera
littorlis; the content ranged from 0.37 g.kg-1 to 10.81 g.kg-1. 2 Iron plaques
have a certain enrichment effect on the heavy metals in the sediments. The
contents of heavy metals in the iron plaques vary with the plant species, being
the highest in A. ilicifolius and the lowest in H. littorlis. This enrichment
also varies with the element species:Mn content changed from 0.11 g.kg-1 to 2.67
g.kg-1; the highest contents of Pb, Zn, Cu, As, and Cr changed from 117.44 mg.kg
1 to 189.69 mg.kg-1; and the highest contents of Cd, Ni, Co. and Sb changed from
34.84 mg.kg-1 to 63.34 mg.kg-1. The content of Zn in the iron plaque is
negatively correlated with the other heavy metal contents (P<0.001), indicating
that Zn might compete with the other elements. 3 Sediment pH significantly
affects the content of iron plaque and the accumulation of Mn in the iron plaque
(P<0.05). The water content and salinity of the sediments are positively
correlated with the contents of heavy metals Cr and Co in the iron plaque
(P<0.05). 4 The distribution of iron plaques and their heavy metal contents in
different parts of the roots of the mangrove plants follow the order:root tip >
root middle > root base.
PMID- 29965013
TI - [Spatial Distribution of DDTs and PCBs in Wild Fish from Hong Kong Coastal Areas
and Potential Human Health Risk Assessment].
AB - To examine the distributional patterns of persistent organic pollutants in the
wild fish of Hong Kong and assess the health risks associated with consuming
them, two typical kinds of persistent organic pollutants, such as
dichlorodiphenyltrichloroethane (DDTs) and polychlorinated biphenyls (PCBs), were
determined in 31 kinds of fishes caught from the coastal areas of Hong Kong. The
results indicate that the concentrations of DDTs and PCBs in the wild fishes were
in the ranges of 0.44-17 ng.g-1 and 0.028-6.3 ng.g-1, respectively, which were at
the low end of the global ranges. Spatially, the lowest concentrations of DDTs
and PCBs were found in the fishes occurring in the west of Lantau Island and Tolo
Harbor. Furthermore, the feeding habits and living environments of the fishes
could have some influence on the accumulation of DDTs and PCBs in them. Source
diagnostics indicated that DDTs in these fishes mainly originated from historical
residues, but the fishes which migrate for relatively longer distances may be
subject to DDT contamination in the estuaries. Finally, human health risk
assessments suggested that the increased potential lifetime cancer risk of local
adolescences and adults exposed to DDTs and PCBs via wild fish consumption was
high. Therefore, the local residents in Hong Kong should reduce their daily
intake of wild fish caught from the surrounding coastal regions.
PMID- 29965014
TI - [Pollution Characteristics of PAHs in Soil from a Remote Mountain Wetland-Dajiuhu
Lake, Shengnongjia].
AB - Ten sampling points were distributed approximately equidistantly in the Dajiuhu
lake wetland, and soils from the depths 0-10 cm, 10-20 cm, and 20-30 cm were
collected in April 2012. Gas chromatography-mass spectrometry (GC-MS) was used to
analyze the remote mountain wetland shallow soils, and 16 kinds of USEPA priority
controlled polycyclic aromatic hydrocarbon (PAH) pollutants were identified. The
?16PAHs content ranges of the shallow soils of this region were 48.55-984.73 ng.g
1, 14.36-806.47 ng.g-1, and 12.84-1191.53 ng.g-1 in the 0-10 cm, 10-20 cm, and 20
30 cm layers, with a mean of 302.94 ng.g-1, 142.98 ng.g-1, and 208.68 ng.g-1 in
the three layers, respectively. The concentrations of seven carcinogenic PAHs
ranged from 21.20-844.29 ng.g-1, 2.96-592.06 ng.g-1 and 0.66-964.70 ng.g-1 in the
three soil layers, with means of 197.25 ng.g-1, 93.16 ng.g-1, and 147.16 ng.g-1
that accounted for 65.12%, 65.13%, and 69.08% of the total PAHs in the three soil
layers, respectively. The concentrations of PAHs in the areas with peat were
significantly higher than that in the soil. PAHs having 4-6 rings were the
dominant ones. The ratios IcdP/(IcdP+BghiP) and Pyr/BaP showed that the PAHs in
the shallow soil form the Dajiuhu lake wetland mainly came from burning fossil
fuels and wood. In recent years, the entry of tourist vehicles has contributed
significantly to the increase in PAHs. The regression analysis on peat surface
layer single body PAH and total PAHs showed that Chr, BbF, IcdP, and BaA could be
used as a signaling property of mountain wetland PAH pollution.
PMID- 29965015
TI - [Migration and Transformation of Mercury in Unsubmerged Soil and Sediment at One
Typical Forest Reservoir in Southwest China].
AB - Mercury (Hg) has been regarded as a global pollutant due to its volatility and
toxicity. The sediment in the reservoirs or lakes is an important compartment for
Hg methylation and it has also been considered as a sensitive area of Hg. In this
study, a typical forest reservoir surrounding by evergreen broad-leaved forest in
Chongqing of southwest China was selected to investigate the migration and
transformation of Hg in unsubmerged soil and sediment. The unsubmerged soil and
sediment were also replaced to each other to observe the dynamics of THg and
TMeHg concentrations in equilibrium processes. The results were as follows:1 The
THg and TMeHg mean concentrations in Dahonghai reservoir water were (1.89+/-0.72)
ng.L-1 and (0.13+/-0.04) ng.L-1, respectively, which were lower than the first
class water quality standards in environmental quality standard of China and
other reservoirs or lakes, implying that this study area did not affect by Hg
pollution. Meanwhile, the THg and TMeHg mean concentrations in unsubmerged soil
and sediment were also lower than those in other reservoirs or lakes. 2 Seasonal
variations of THg and TMeHg concentrations in reservoir water and soil were both
observed higher in warm seasons, and more obvious variations occurred for TMeHg
which probably influenced by meteorological parameters, such as, temperature and
rainfall. 3Compared with unsubmerged soil, the THg and TMeHg mean concentrations
in sediment were both elevated, suggesting the sediment was an important sink of
Hg. While, the sediment would be a source of Hg (especially TMeHg) with a high
THg and TMeHg level. 4 The THg and TMeHg mean concentrations in unsubmerged soil
and sediment after situ replacement were equilibrated with ambient soil in a
short time (one or two months), implying the hydro-fluctuation belt of reservoir
promoting the geochemical cycle of Hg.
PMID- 29965016
TI - [Accumulation of Cd and Its Risks in the Soils of the Xijiang River Drainage
Basin in Guangxi].
AB - To understand the distribution and risk of soil cadmium (Cd) in the Xijiang River
drainage basin in Guangxi, a total of 2512 soil samples were collected nonferrous
metal mining area, farmland (paddy soils and dryland soils) and the background
soils, in the Xijiang River drainage basin in Guangxi.The results showed that Cd
concentration was 0.514 mg.kg-1 in background soils significantly higher than
previously resulted(0.148 mg.kg-1)and that in Guangxi background soil(0.267 mg.kg
1). The geometric average concentration of Cd in dryland soils, paddysoils and
mining soils was 0.559, 0.787, 5.71 mg.kg-1, respectively, which were
significantly higher than background soils. The Cd concentration exceeded the
background soils and baseline by 51.2% and 35.2% in dryland soil, 66.7% and 39.6%
in paddy soil, 77.8% and 71.4% in mining soil, high Cd concentration occurred in
the Nandan County, Dahua County, Duan County, Huanjiang County and Yizhou City,
as well as Liujiang County, These regions have developed severe and even
extremely serious pollution, medium-high pollution accumulation and higher
extremely high potential ecological risks. The Cd-pollution in soils in
agricultural and mining soils in upstream of Xijiang River in Guangxi is serious,
due to mining activities and high Cd geological background. People in the mining
area and surrounding areas who live on local crops, vegetables, may expose to the
Cd-pollution. It is recommended to further develop a Cd risk assessment through a
soil-plant-human system, taking appropriate measures to control risk.
PMID- 29965017
TI - [Effects of Long-term Fertilization Regimes on As Accumulation in Upland Red
Earth and the Crops Growing on It].
AB - To investigate the effects of different long-term fertilization treatments on
arsenic (As) accumulation in upland red earth and the crops growing on it,
different fertilization treatments, including no fertilization (CK),
fertilization with chemical fertilizers containing nitrogen, phosphorus and
potassium (NPK), fertilization with swine manure (M), and fertilization with
chemical fertilizers plus manure (NPKM), in a long-term fertilization site
located in Qiyang County, Hunan Province, were selected.. The results showed that
after 26 years of fertilization, both the total and available As concentrations
in the soils were significantly improved in the fertilized soils (i.e., NPK, M,
and NPKM) when compared to the CK soil. Meanwhile, NPK treatment had the highest
As concentration (44.68 mg.kg-1), which was higher than the national standard
value (40 mg.kg-1) in acidic soils. Fertilization practices had the biggest
impacts on the non-specifically-absorbed As, followed by the residual As, and the
well-crystallized hydrous oxides of Fe and Al absorbed As, but minor impacts on
the amorphous and poorly-crystalline hydrous oxides of Fe and Al-absorbed As, and
the specifically absorbed As. Furthermore, NPKM treatment significantly decreased
the concentrations of As(III) and As(V) in the soils, when compared to the other
treatments. Also, M treatment could cause the accumulation of As in the grains
and straws in corn. In contrast, M treatment could not cause the accumulation of
As in the grains and straws in wheat. Furthermore, correlative synchrotron
radiation-based FTIR and micro X-ray fluorescence spectromicroscopic analysis
showed that As had a similar distribution pattern with clay -OH and C-OH.
PMID- 29965018
TI - [Effects of a Tribasic Amendment on Cadmium and Arsenic Accumulation and
Translocation in Rice in a Field Experiment].
AB - An in-situ paddy field experiment was carried out to study the influence of a
tribasic amendment (QFJ, hydroxyapatite+zeolite+biochar) on Cd and As
accumulation and translocation in rice grown in soil contaminated with cadmium
and arsenic, with the concentrations of soil Cd and As being 3.58 mg.kg-1 and
124.79 mg.kg-1, respectively. The results showed that, after application of QFJ,
the pH, CEC, and OM contents of the rice rhizosphere soil tended to increase. The
exchangeable concentrations of Cd and As were reduced from 0.37 mg.kg-1 and 0.07
mg.kg-1 to 0.12 mg.kg-1 and 0.04 mg.kg-1, respectively. The concentrations of Cd
and As in rice tissues decreased after in-situ restoration. When 9.00 t.hm-2 of
QFJ was applied, the Cd concentration in brown rice was reduced from 0.46 to 0.18
mg.kg-1, and that of inorganic As was reduced from 0.25 to 0.16 mg.kg-1, both
lower than 0.2 mg.kg-1, meeting the requirement set by the National Food
Standards (GB 2762-2012). QFJ application decreased the Cd and As bioaccumulation
capacity of the roots and decreased the rice plant's capacity of Cd translocation
quantity from the underground parts to the aerial parts; at same time, the Cd
transferring capacity of the roots and the As transferring capacity in straw and
husk were also decreased.
PMID- 29965019
TI - [Quantitative Relationship Between Paddy Soil Properties and Cadmium Content in
Rice Grains].
AB - Rice is a crop with the potential for high accumulation of Cd, which can be
affected by many factors. Sixty pairs of soil and rice samples from different
plots were collected and analyzed, in order to understand the quantitative
relationships between the Cd content in soil and the properties of soil and the
Cd content in rice grains under field conditions, by simple and multiple
regression analyses. The results showed that the Cd contents in soil and rice
grains ranged from 0.15-2.54 mg.kg-1 and 0.02-2.00 mg.kg-1, respectively.
According to the result of simple regression analysis, there were significantly
positive correlations (P<0.01) between the Cd contents in soil and rice grains
(r=0.392); the pH, SOM, and CEC in soil also had certain effects on Cd
accumulation in rice grains, which were not significant, however. When the soil
pH was<6.5, the Cd content in rice grains increased with increasing soil pH, but
decreased with increasing soil pH when the soil pH was>6.5. The Cd content, pH,
SOM, and CEC in the soil and the Cd content in rice grains were analyzed by
multiple regression analysis, and five equations, which all reached extremely
significant levels (P<0.01), were obtained. The equation that included the four
variables (Cd content, pH, SOM, and CEC in soil) had the most r, and it could
predict the Cd content in rice grains better, given the conditions of the present
study.
PMID- 29965020
TI - [Effect of Ca-bentonite on Cu and Zn Forms in Compost and Soil, and Their
Absorption by Chinese Cabbage].
AB - Aerobic composting was conducted to evaluate the effects of the different ratios
(0%, 2.5%, 5%, 7.5%, and 10%) of Ca-bentonite (CB) on the speciation of Cu and Zn
during pig manure composting, while pot experiment was performed to investigate
the role of CB-added compost on the bio-availability of Cu and Zn to Chinese
cabbage and its biomass. The results showed that the exchangeable fractions of Cu
and Zn decreased, while their oxidized and residual fractions gradually increased
during composting; CB addition reduced the distribution ratios of bio-available
Cu and Zn in mature compost by approximately 19.84%-48.90% and 4.94%-16.39%,
compared to those in the 0% CB-added treatment, and the best result was found in
the 10% CB-added treatment.. Meanwhile, the pot experiment confirmed that the
addition of compost considerably increased soil organic matter (OM) and
electrical conductivity (EC) but decreased soil pH value. On the contrary, the
application of CB effectively decreased EC and increased soil pH but inhibited OM
mineralization in soil as compared to non-amended treatment. While addition of
compost significantly increased plant dry biomass as compared to that with soil
alone, maximum biomass was obtained[(6.51+/-0.34) g.pot-1] in 10% CB-added
compost. After the application of CB-added compost, the contents of the bio
available factions of Cu in the harvested soil increased, while the contents of
the exchangeable fractions of Zn decreased by 38.91%, 43.69%, 46.02%, 45.12%, and
54.65%, respectively. The absorption of Cu and Zn by Chinese cabbage was
considerably reduced after the application of compost, while the uptake of Zn in
the plant declined as the CB rates increased, and the absorption of Cu increased.
The study indicated that 10% CB addition could significantly reduce the
bioavailability of Cu and Zn in compost, and also showed a continuous effect on
restricting the bioavailability of Zn after land utilization. Meanwhile CB
amendment enhanced Chinese cabbage biomass and reduced the uptake of Zn.
PMID- 29965021
TI - [Effects of Short-term Exogenous Nitrogen and Carbon Input on Soil Respiration
Under Changing Precipitation Pattern].
AB - The responses of soil respiration to exogenous carbon (C) and nitrogen (N) inputs
under changing precipitation patterns were explored via in-situ field
experiments. In 2014, a typical temperate grassland on the Xilin River of Inner
Mongolia was taken as the research site, and soil respiration was measured in the
following treatments:addition of water alone (CK), addition of water + N
fertilizer[CN, 2.5 g.(m2.a)-1], addition of water + labile C[CG, 24 g.(m2.a)-1],
and addition of water + N fertilizer+ labile C[CNG, 2.5 g.(m2.a)-1+24 g.(m2.a)
1], and the correlations of soil respiration with soil temperature, soil
moisture, soil dissolved organic C (DOC), and soil microbial biomass C (MBC) were
analyzed. During the first water application event (FWE) with the frequency of
natural precipitation, cumulative CO2 efflux over 168 hours significantly
increased in the CG and CNG treatments, whereas there was no such change in the
CN treatment. In addition, soil MBC contents in the CG and CNG treatments were
significantly higher than that in the CK and CN treatments, and the correlation
of average soil respiration rate with soil MBC content among these treatments was
positively significant (P<0.05). In contrast with during the FWE, cumulative CO2
efflux over 168 hours and soil MBC content significantly decreased during the
second water application event (SWE) with no natural precipitation (P<0.05),
whereas soil DOC content significantly increased (P<0.05). The cumulative CO2
efflux over 168 hours significantly decreases in the CN and CG treatments
(P<0.05).During both the water application events, soil respiration rate had a
positive relationship with soil temperature and soil volume water content
(P<0.05). Therefore, it is proposed that the distribution of natural
precipitation influences soil water content, which controls the effects of
exogenous C and N on soil respiration in semiarid grassland ecosystems.
PMID- 29965022
TI - [Effects of Simulated Precipitation Reduction on Soil Respiration in a Soybean
Winter Wheat Rotation Cropland].
AB - To investigate the effects of precipitation reduction on soil respiration in
rainfed croplands, a field experiment was performed in a soybean-winter wheat
cropland. A randomized block design including three treatments, viz. control
(CK), 20% precipitation reduction (P20%), and 40% precipitation reduction (P40%),
was used. Seasonal variabilities in soil respiration, soil temperature, and soil
moisture were measured. Rates of soil CO2 production, nitrification and
denitrification, and harvested crop biomass were also measured. Results indicated
that the seasonal mean soil respiration rates for CK, P20%, and P40% treatments
in the soybean growing season were (4.91+/-0.67), (4.19+/-0.39), and (4.35+/
0.32) MUmol.(m2.s)-1, respectively. There was no significant difference (P>0.05)
in the mean soil respiration rates between treatments during the soybean growing
season. The seasonal mean soil respiration rates for CK, P20%, and P40%
treatments during the winter wheat growing season were (2.39+/-0.17), (2.03+/
0.02), and (1.94+/-0.05) MUmol.(m2.s)-1, respectively. There was a significant
(P<0.05) difference in the mean soil respiration rates between treatments during
the winter wheat growing season. Precipitation reduction decreased the soil CO2
production rates, but had no obvious impacts on soil nitrification and
denitrification rates. Precipitation reduction had no significant (P>0.05)
effects on the root, shoot, and seed biomass of soybean, but significantly
(P<0.05) decreased the root, shoot, and seed biomass of winter wheat. Soil
temperature was the main driver of the seasonal variation in soil respiration.
Soil respiration increased exponentially with the increase in soil temperature.
There was no significant (P>0.05) difference in the coefficient of temperature
sensitivity (Q10) between different treatments. Based on the precipitation
reduction experiments of duration longer than one year in previous studies and in
our present study, a significant linear regression relationship between the
amount of reduced soil respiration and the amount of precipitation reduction was
found, indicating that substantial precipitation reduction showed more obvious
inhibition effects on soil respiration. This study also suggested that the
effects of precipitation reduction on soil respiration varied between crop
growing seasons, which may be attributed to the different precipitation
intensities in different growing seasons.
PMID- 29965023
TI - [Seasonal Variation in Nitric Oxide Emission from an Agricultural Headwater Ditch
in the Hilly Purple Soil Area and the Factors Influencing Emission].
AB - Agricultural headwater ditches are important pathways of reactive nitrogen loss
from adjacent croplands, and also act as hotspots for reactive nitrogen
transformation. In this study, NO emissions from a typical agricultural ditch in
the hilly area of central Sichuan Basin were measured by the closed static
chamber-chemiluminescence method, from December 2014 to November 2015. The
results showed that the cumulative NO emissions from the sediment-water interface
without vegetation (NV) and the ditch ecosystem with natural vegetation (V) were
0.4 g.(hm2.a)-1 and 14.17 g.(hm2.a)-1, respectively. The combined annual NO
emission flux for the agricultural headwater ditch ecosystem was 11.27 g.(hm2.a)
1, with a mean NO emission rate of 0.13 MUg.(m2.h)-1. A net source of NO from the
ditch ecosystem only occurred in summer, which had a significantly higher
cumulative NO emission than those in the other seasons. The seasonal variation in
NO emissions was mainly regulated by the seasonal changes in NO3--N
concentrations and temperature in the overlying water. Meanwhile, the presence of
vegetation in the ditch ecosystem significantly increased NO emission rates,
whereas it did not markedly influence the annual NO emission.
PMID- 29965024
TI - [Effects of Seasonal Asymmetric Warming on Soil CO2 Release in Karst Region].
AB - Seasonal asymmetric warming is one of the distinguishing features of global
warming. However, if this feature is not considered in studying the effects of
global changes on terrestrial ecosystems, it might probably cause
misunderstanding of these studies. The releasing features of soil CO2 in Karst
regions under various warming scenarios were simulated following a four-year
continuous warming period using infrared radiators. A total of six treatments was
arranged:no warming (ambient temp, CK); symmetric warming (ambient plus 2.0C full
year, SW); and, lowly, moderately, highly, and extremely asymmetric warming
(ambient plus 2.5C/1.5C, 3.0C/1.0C, 3.5C/0.5C, and 4.0C/0C in the winter
spring/summer-autumn seasons, respectively, LAW, MAW, HAW, and EAW). The results
showed that compared to CK, soil CO2 efflux in all the warming plots
significantly increased by 0.26 MUmol.(m2.s)-1, or 17.41%. In the winter-spring
seasons, soil CO2 efflux in the warming treatments increased by 0.23 MUmol.(m2.s)
1. The Q10 values ranged from 1.53 to 3.24 with an average of 2.23 under the
scenario of warming up by 2.0C. The warming-induced contribution of CO2 efflux in
the summer-autumn seasons (80%) was obviously higher than that in the winter
spring seasons (20%) in the SW treatment, whereas the mean contribution in the
summer-autumn seasons (46%) was closer to that in the winter-spring seasons (54%)
in the asymmetric warming treatments. Both soil CO2 efflux and Q10 showed a
tendency towards decrease with the increase in the asymmetry of warming under the
five warming scenarios. The soil CO2 efflux in the SW treatment was significantly
(P<0.05) higher than those in the MAW, HAW, and EAW treatments. The Q10 values in
the summer-autumn seasons was larger than those in the winter-spring seasons
under each warming treatment or across all warming treatments, which was probably
related to soil water content, soil microbe, dissolved inorganic carbon, and
vegetation growth. The results revealed that it may potentially overestimate the
effects of global warming on soil CO2 releasing subject to symmetric warming.
PMID- 29965025
TI - [Source Apportionment of Volatile Organic Compounds and Health Assessment of
Benzene Series in Northern Suburb of Nanjing in Winter].
AB - Volatile organic compounds (VOCs) in the atmosphere of the north suburb of
Nanjing in December 2015 were determined by GC5000 online gas chromatography,and
the main composition and characteristics of VOCs were analyzed by using the PMF
receptor model sources of VOCs parsing.The United States Environmental Protection
Agency (EPA) human exposure analysis and evaluation method in the United States
were used to evaluate Human health risk of benzene series.The results showed that
there were 6 sources in the PMF mode.Natural gas leakage accounted for
32.05%,automobile exhaust accounted for 18.99%,solvent use 13.67%,industrial
emissions 2 13.20%,gasoline volatile 11.72%,and industrial emissions 1(chemical
type)10.36%.The high value areas of the emission source were in accordance with
the location of pollution sources surrounding the observation point.The B/T ratio
was 0.74,which was at a relatively high level.The noncarcinogenic risk hazard
quotient value HQ at 06:00 reached the highest value.HQ risk values were within
the safe range specified by EPA.HQ of each source was as follows:automobile
exhaust emissions 20.67*10-2,solvent use 6.97*10-2,natural gas leakage 6.34*10
2.In the carcinogenic risk of benzene,automobile exhaust emissions was 4.11*10
6,and natural gas leakage was 1.09*10-6,both were higher than the EPA specified
safety threshold.
PMID- 29965026
TI - [Size Distribution and Mixing State of Black Carbon Aerosol in Nanjing During a
Heavy Winter Pollution Event].
AB - In December 2013,a lasting haze pollution event occurred in the Central and East
regions of China.Here in this paper,using a single-particle soot photometer
(SP2),we studied mass concentrations,mixing states,and size distributions of
black carbon (BC) in this event.The results showed that BC mass concentration in
Nanjing during the observation period was in the range of 1.01-14.05 MUg.m-3 with
an average of 4.39 MUg.m-3,showing the characteristics of double peaks for
lighter pollution,andhigh in the nighttime and low in the daytime during heavier
pollution.Using the relative coating thickness (Dp/Dc) to define mixing state of
black carbon,diurnal variations were higher in early morning and noon when
slightly polluted,and lower during rush hour,indicating the degree of BC ageing
was deeper in the morning and afternoon,with fresher particles near the ground
source emissions during rush hour.The relative coating thickness did not vary
greatly throughout the day when heavily polluted,which was expected to be linked
to regional pollutants and it also showed Gas-solid transformation under high
relative humidity.The average mass and number size distribution had single
peaking with the same BC volume-equivalent diameter in different degrees of
pollution,with the peak diameter at 100 nm for the number distribution when
heavily polluted,at 91 nm when slightly polluted,and at 210 nm for the mass
distribution regardless of the degree of pollution.We could find regional
differences of BC sources by comparing the observed research worldwide.This study
has very important reference value for the in-depth understanding of BC pollution
in Yangtze River Delta.
PMID- 29965027
TI - [Interactive Effects of the Influencing Factors on the Changes of PM2.5
Concentration Based on GAM Model].
AB - In this paper,the generalized additive model (GAM) was introduced to analyze the
interactive effects of the influencing factors on the change of PM2.5
concentration during 2013-2015 in Nanjing city.The results showed as
follows:PM2.5 and its influencing factors appeared to follow normal
distribution.There were strong correlations among the influencing
factors,especially among the temperature (TEM),pressure (PRS) and water vapor
pressure (VAP).For the single influencing factor GAM models of PM2.5
concentration,all influencing factors passed the significance test.Moreover,the
equation fitting degrees of SO2,CO,and NO2 were much higher.In the multiple
influencing factors GAM models of PM2.5 concentration,the contribution of the
SO2,CO,NO2,O3,precipitation (PRE),wind and relative humidity (RHU) to the change
of PM2.5 concentration was 73.9% with significant impacts on the change of PM2.5
concentration.Based on the diagnostic analysis of the effect of multi factors on
the change of PM2.5 concentration,there were linear relationship between PM2.5
and SO2,NO2 and wind,and non-linear relationship between PM2.5 and CO,O3,PRE and
RHU.The GAM models,which considered the interaction of SO2 respectively with
CO,PRE and RHU,the interaction of CO respectively with NO2,O3,PRE,Wind and
RHU,and the interaction of NO2 respectively with Wind,PRE and RHU,all passed the
significance test (P<0.01 or P<0.05).The interaction of SO2,CO and NO2
respectively with other factors such as meteorological factors had the most
important influence on the change of PM2.5 concentration.At last,through the
visualized three-dimensional map of the GAM models considering the interaction of
the influencing factors on the PM2.5 concentration,the interactive effects of the
influencing factors on PM2.5 concentration were quantitatively modeled.Our
results demonstrated that GAM could be used to quantitatively analyze the
interactive effect of the influencing factors on the change of PM2.5
concentration.Therefore,the research method is innovative and important for PM2.5
pollution and control.
PMID- 29965029
TI - [Greenhouse Gas Fluxes at Water-Air Interface in Small Pond Using Flux-Gradient
Method Based on Spectrum Analyzer].
AB - As an important part of inland waters,small pond is a neglected source of
greenhouse gas.The main objective of the study was to quantify greenhouse gas
fluxes (CO2 and CH4) from small pond in the Yangtze Delta using flux-gradient
method.The results showed that:1 zero-gradient test indicated that the flux
measurement precision for water vapor,CO2,and CH4 was 7.525 W.m-2,0.022 mg.(m2.s)
1,and 0.054 MUg.(m2.s)-1,respectively.During the test period,84%,80%,and 94% of
half-hourly flux data for H2O,CO2,and CH4 were higher than the zero-gradient
measurement precision.2 Based on the measurement,the small pond was the source of
CO2 and CH4 for the atmosphere in summer,the mean emission flux of CO2 and CH4
was 0.038 mg.(m2.s)-1 and 0.889 MUg.(m2.s)-1,respectively.The CH4 emission fluxes
from the small pond were more higher than the median value of emission for global
lakes.The results indicated that greenhouse gas emission from small pond was an
important part for estimating inland water greenhouse gas emissions,especially
for CH4 emission.These results can provide scientific reference for making
emission inventory of regional greenhouse gas.
PMID- 29965028
TI - [Particle Size Distribution and Diffusion for Simulated Cooking Fume].
AB - Studying particle size distribution and dispersion characteristics of cooking oil
fume can help to analyze the influence of the particles on indoor air quality and
the health of the residents.Electrical low pressure impactor (ELPI) was employed
to measure the number and mass concentration of the particles size range of 0.03
10 MUm at two different locations in the kitchen space with smoke exhaust on and
off,respectively.The cooking particles were mostly located at below 655 nm.The
smoke exhaust with open condition could remarkably decrease the kitchen's cooking
fume.The number concentration of particles decreased from 2.8*106 cm-3 to 2.3*105
cm-3,and PM2.5(aerodynamics diameter <=2.5 MUm particulate matter) mass
concentrations decreased from 85.9 mg.m-3 to 6.2 mg.m-3.The sucking efficiency of
smoke exhaust for PM10 was higher than PM2.5.The number concentration of
particles could be declined by 65%,and the cooking fume of PM2.5 could be
declined by 75% during the diffusion process detected at the area of 3 m far away
from the area where cooking took place.The distribution of PM2.5 mass
concentration field of oil fume was simulated by computational fluid dynamics.The
temperature field distribution of oil fume was monitored by infrared
camera,presenting sector diffusion with the temperature decreasing from 70C to
room temperature.
PMID- 29965031
TI - [Comparisons Between Seasonal and Diurnal Patterns of Cave Air CO2 and Control
Factors in Jiguan Cave, Henan Province, China].
AB - Cave air CO2 makes notable impacts on the deposition and dissolution of
speleothem,affecting the stability of carbonate landscape and comfort of tourist
in show caves.Cave air CO2 is a key factor of karstification occurrence.Studying
the mechanism of cave air CO2 variation is important for understanding the
pattern of karstification and cave protection.In order to understand the temporal
and spatial variation characteristics and its possible controlling factors,inside
and outside cave air CO2,hydrogeochemical index,temperature,relative humidity as
well as precipitation and tourist amount were observed in the Jiguan Cave,which
lies in the west Henan Province of south-north geographical boundary of
China.Nearly five years monitoring of air CO2 of Jiguan Cave was carried out from
December,2011 to May,2016.A diurnal monitoring was performed from 19 May,2016 to
20 May,2016.The results indicated that the cave air CO2 showed notable spatial
and seasonal variations.1 From the spatial variation,the sites closer to cave
entrances,affected by strong cave ventilation,had lower pCO2.In addition,the
special structure of Jiguan Cave and soil air pCO2 variation,vegetation
respiration and soil microbial activity,which in turn were associated with
changes in climate and environment also contributed to the variation of cave air
pCO2.2 On a seasonal scale,cave air CO2 was higher in summer and lower in
winter.This variation of cave air CO2 was mainly influenced by tourism activity
as well as karstification.3 Tourist amount was the mainly factor that influenced
the variation of cave air CO2 on a daily scale.Because of tourism activity,cave
air CO2 was increased,and also cave environment was disturbed.All of these
intimidate the better conservation of cave environment.
PMID- 29965030
TI - [Diurnal Variations of Concentration of Porewater Dissolved CH4 and CO2 in a
Brackish Marsh Dominated by Cyperus malaccensis and Phragmites australis During
Neap and Spring Tidal Days in the Minjiang River Estuary].
AB - Understanding of diurnal variation of soil porewater dissolved CO2 and CH4
concentration plays an important role in revealing carbon cycling in estuarine
wetlands.During neap and spring tidal days in April and September 2010,the
diurnal variations of soil porewater dissolved CO2 and CH4 concentrations and
main impacting factors in a brackish marsh ecosystem dominated by two species of
Cyperus malaccensis(brevifolius) and Phragmites australis(common reed) were
determined in the ShanYutan in the Min River estuary,southeast China.The results
showed that:1 the soil porewater dissolved CH4 concentration during the spring
and neap tidal days in April and September ranged from 88.20 to 190.74,53.42 to
141.24,16.27 to 81.89 and 44.90 to 88.53 MUmol.L-1,respectively.The mean of
dissolved CH4 concentration was higher at nighttime than at daytime during the
spring and neap tidal days in April,but the mean of dissolved CH4 concentration
was higher at daytime than at nighttime during the spring and neap tidal tidal
days in September.2 the soil porewater dissolved CO2 concentration during the
spring and neap tidal days in September ranged from 19.33 to 40.1 MUmol.L-1 and
9.69 to 29.96 MUmol.L-1,respectively,and the dissolved CO2 concentration during
daytime was lower than that at night;3 the mean of dissolved CO2 concentration
was lower during the inundation period than in the exposed soil surface
period,but the mean of dissolved CH4 concentration was higher during the
inundation period than in the exposed soil surface period.
PMID- 29965032
TI - [Fluorescence Spectral Characteristics of Fluorescent Dissolved Organic Matter
(FDOM) in the Surface Sediments from Lihu Lake].
AB - This study investigated the spectral characteristics of fluorescent dissolved
organic matter (FDOM) in sediments of Lihu Lake using three-dimensional
excitation-emission matrix fluorescence spectroscopy (EEMS),and discussed the
correlation between source of FDOM and organic or inorganic nitrogen.The results
indicated that the surface sediments in Lihu Lake consisted of three fluorescence
fractions (II),humic-like C1(240,310/420 nm),C2(260,360/460 nm),and tryptophan
like C3(225,275/340 nm).The total fluorescence intensity ranged from 49.97 to
159.19 R.U..g-1,and decreased from east to west with higher values in coast
district than in lake center.The relative proportions of C1,C2,and C3 were
33.63%,26.87% and 39.49%,respectively.The fluorescence index (FI),biological
origin index (BIX),and humification index (HIX) ranged from 1.96 to 2.22,0.69 to
0.94,and 2.62 to 4.39.It indicated that the main source of FDOM in Lihu Lake was
from endogenesis,and mainly derived from microbes,algae and other newly
autochthonous sources.The results illustrated,the fluorescence intensity had
significant correlation with organic and inorganic nitrogen (P<0.01),and had
higher correlation with inorganic nitrogen.
PMID- 29965033
TI - [Sedimentary Characteristics and Sources of Organic Matter in Sediments of
Dianchi Lake].
AB - Sediment columns in the southeast and east of Dianchi Lake were taken as the
object of the study to determine ages by 210 Pb dating method.The contents and
sediment fluxes of total organic carbon (TOC) and n-alkanes of the sediments were
investigated,and organic sources were tracked according to the relevant indexes
of n-alkanes.The results indicated that TOC contents and sediment fluxes of two
sampling sediments both presented an increasing trend on the whole;Sediment
fluxes of n-alkanes varied as three stages:increasing period,decreasing period
and re-increasing period.When the sediment fluxes of n-alkanes and TOC both went
up,it showed that they had the same sources:sediments in the lake and carried by
the rivers;From 1980s to the end of 20th century,sediment fluxes of n-alkanes
were going down while those of TOC were going up.This result means there was a
big difference in the sources of n-alkanes and TOC.The bacteria and algae in the
lake made a great contribution to n-alkanes while TOC was mainly influenced by
sediments in the lake and carried by the rivers.n-alkanes of the two sampling
sites both ranged from C12 to C35.Based on the basic features and relevant
indexes of n-alkanes,we proposed that emergent plants made big contributions to
the sources of organic matter in the sediments of Dianchi
Lake,simultaneously,bacteria and algae had significant contributions to the
sources of organic matter in shallow depth of Dianchi Lake.
PMID- 29965034
TI - [Seasonal Variation of Colloid Particles in the Shallow Well Water of a Small
Watershed of Purple Soil].
AB - Colloids are the major carriers of various contaminants during the downward
transport into groundwater.To explore the long-term dynamics of colloid in the
groundwater and its influencing factors,a one-year monitoring of colloid
concentration and water physicochemical parameters was carried out in the shallow
wells in a purple soil dominated watershed in the hilly region of central
Sichuan.The results indicated that colloid concentrations within a year had a
strong seasonal variation with the coefficient of variation being larger than
0.5.The maximum of colloid mass concentration could reach as high as 14.68 mg.L
1(the corresponding number concentration being 1.34*109 L-1),which occurred in
the non-rainy season and was caused by the physical perturbations from water
taken.Physical perturbations of rainfall led to the distinct peaks of colloid
concentrations in the well water at the early stages of rainy season while it did
not occur at the end of the rainy season even upon heavy storm.Water chemistries
(EC,Ca2+,Mg2+,DOC) showed the dominant role in determining colloid concentrations
and status in the well.The facilitated transport of contaminants (i.e.pesticides
and heavy metals) due to the increased colloids in the shallow well water at the
early stages of rainy season would potentially pose a great threat to the
drinking water safety in the study area.Therefore,it is strongly suggested to
increase the monitoring frequencies in terms of colloid concentrations and well
water physicochemical parameters following the large rainfall events during this
period.
PMID- 29965035
TI - [Deposition Characteristics of Suspended Solids and the Response of Dissolved
Nutrients in Spring in the Western Lakeside of Taihu Lake].
AB - To reveal the spatiotemporal characteristics of nutrients in the deposition
process of suspended solids in lakeside zone,in situ deposition tests were
performed in the western lakeside of Taihu Lake,and the contents of TP,TN,NH4+-N
and NO3--N were measured and analyzed.The results showed that the deposition
fluxes in the western lakeside of Taihu Lake ranked as follows:artificial reed
areas >non-vegetation nearshore areas >natural reed areas >non-vegetation
offshore areas,with their average values of (1383.40+/-925.60),(1208.67+/
743.50),(278.72+/-142.53),(245.58+/-154.25) g.(m2.d)-1,respectively.From the 6th
day,the deposition volume steadily increased,with the deposition rate larger than
the decomposition rate.Through the 15-day continuous in situ observation,the
content of TP in nearshore zone was 2-3 folds larger than that of offshore
zone,and the content of NH4+-N was significantly different from that of NO3--N in
the settlement bottle (P<0.01).The deposition volume was significantly and
positively correlated to both TN and NH4+-N contents in the water column
(P<0.01,n=42),suggesting that the TN and NH4+-N contents in the overlying water
increased with the deposition fluxes.The correlation coefficient between TN and
NH4+-N was 0.84,implicating that the increase of deposition flux may accelerate
the mutual transformation between different forms of nitrogen.These findings
should be taken into account in the current control of black blooms and nutrient
management in Taihu Lake.
PMID- 29965036
TI - [Correlation Between LDI-based Land Use Types and Water Quality in Sanshan Island
of Taihu Lake National Wetland Park, Suzhou].
AB - Sanshan island of Taihu Lake National Wetland Park in Suzhou was taken as a case
study to explore the relationship between land use types and water quality under
different spatial and temporal conditions.Firstly,principal component analysis
was used to calculate the comprehensive index of water quality for a given
sampling site.Secondly,landscape development intensity index (LDI),which can
represent combined effects of land use types,was calculated based on GIS spatial
analysis technology.Finally,overall correlation between water quality and land
use types was obtained by using Pearson correlation analysis.The results showed
that the water quality varied with the spatial distribution of the wetland
park.Totally,water quality of west region was good and water quality of east
region was poor;Built-up land and water quality integrated index exhibited
obvious positive correlation.And natural water and water quality index was
significantly negatively correlated;By building relationship of water quality
index and LDI index within 100,150,200,250,300,350,400,450 and 500 m radius
buffer,Pearson's r values between them were
0.641,0.678,0.691,0.685,0.691,0.695,0.680,0.653 and 0.649 respectively
(P<0.01).These statistics indicated obvious and stable overall correlation
between land use types and water quality.This can reflect a variety of land use
types' comprehensive effects on wetland water quality,and partly overcome the
weakness of incomplete and difficult explanation for water quality changes with
single type of land use.
PMID- 29965037
TI - [Response Characteristics of Algal Chlorophyll-a to Nitrogen, Phosphorus and
Water Temperature in Lake Erhai Based on Quantile Regression].
AB - Based on water quality monitoring data of Lake Erhai from 1990 to 2013,the yearly
and seasonally response characteristics of algal chlorophyll-a to total nitrogen
(TN),total phosphorus (TP) and water temperature was investigated using quantile
regression method.It indicated that water temperature was always the primary
limiting factor of algal biomass indicated by chlorophyll a (Chl-a) across recent
24 years,but its limiting effect on algal Chl-a content was kept descending
sharply and replaced much by nutrients (e.g.P,N) with the increasing eutrophic
level.Especially the slope values of TP on Chl-a were kept ascending from -0.3 to
0.8.Since 2002,the positive effect of TN on Chl-a presented slow descending
tendency,and P became the most important limiting nutrient factor of algal
growth.According to the seasonal variation analysis,water temperature and N had
dominant effects on algal Chl-a in spring and autumn,but they were replaced by P
in the case of Chl-a>8 mg.m-3 in spring.In summer,N and P had strong interactive
impacts on the algal growth,and the positive effect of P was stronger than that
of N in the case of Chl-a>3 mg.m-3.In winter,algal biomass was co-limited by
temperature and P.It suggested that P reduction is the prior choice of
eutrophication control of Lake Erhai,and simultaneously reducing N load is
necessary in the background of global warming.In addition,so far a emergency
controlling measure should be taken to monitor algal blooming due to sharp
ascending of water temperature within a few days in spring and autumn.
PMID- 29965038
TI - [Seasonal Succession Characteristics of the Morphologically-based Functional
Groups (MBFG) in Deep-water Reservoir].
AB - Morphologically-based functional groups (MBFG) is the basis for a simple way of
distinguishing the phytoplankon to cluster species according to their similar
morphological traits observed by optical microscope.In order to understand the
application of morphologically-based functional groups (MBFG) in the research on
phytoplankton community structure and variation of deep-water reservoir,as well
as the succession characteristics of algae,the Jinpen Reservoir was studied from
August 2011 to July 2013.Using morphologically-based functional groups (MBFG),the
phytoplankton communities found in the reservoir were classified to functional
groups,and the relations between the morphologically-based functional groups
succession and environment cases were explored with redundancy analysis (RDA)
method.The results suggested that five morphologically-based functional groups
were found in the reservoir,namely II,IV,V,VI,VII;The succession of reservoir
algal functional groups had seasonal characteristics,a variety of Morphologically
based functional groups coexisted in spring and summer,while reservoir algal
functional groups were relatively simple in autumn and winter;meanwhile,the
density of each morphologically-based functional group decreased with the
increase of water depth among the environmental factors,morphologically-based
functional groups IV and VI were respectively affected by temperature;the other
water layers of the reservoir morphologically-based functional groups VI was
significantly affected by TN content.
PMID- 29965039
TI - [Change and Influencing Factors of Dissolved Carbon and Dissolved Nitrogen in
Water of the Three Gorges Reservoir].
AB - In order to understand the changes of dissolved carbon and dissolved nitrogen in
the water of Three Gorges Reservoir,this research was carried out once a week by
the bank of Yangtze River in Fuling beach from March 2011 to August 2012,and the
variation characteristics of dissolved C,N composition and their source were
analyzed.The results showed that the concentration of DOC ranged from 0.64 mg.L-1
to 9.07 mg.L-1,and had obvious seasonal change:summer >spring and autumn
>winter.Annual total input of DOC was 1.78*109 kg,the seasonal change trend of
the total input of DOC was similar to that of the concentration of DOC;The
concentration of DTN ranged from 2.59 mg.L-1 to 4.35 mg.L-1:spring >winter
>summer >autumn,annual total input was 1.32*109 kg,the seasonal input changed in
the order of summer >autumn >spring >winter,among them DON,NO3--N accounted for
30.35%-63.45% and 35.87%-67.72%,respectively.DOC was affected by precipitation
and air temperature,and mainly came from the exogenous input,in the spring and
summer its exogenous input increased with the increase of rainfall runoff,but in
the autumn and winter the endogenous contribution increased;DTN was relatively
affected by human emissions and water dilution.Correlation analysis showed that
there was a significant negative correlation between DOC and DON (P<0.05),DOC/DON
ratio usually reflects the source of the DOM,the DOC/DON in the water of three
gorges reservoir ranged from 0.35 to 7.28,the source of DOM had obvious seasonal
characteristics.DOC/DON was the highest in summer,and the DOM mainly came from
watershed erosion;DOC/DON was the lowest in winter,and the DOM mainly came from
living sewage and endogenous field;the DOC/DON ratios in spring and autumn were
higher than those in winter and lower than those in summer,and the DOM sources
included watershed erosion,living sewage and endogenous field.
PMID- 29965040
TI - [Characteristics of Nitrogen and Phosphorus Emissions in the Gufu River Small
Watershed of the Three Georges Reservoir Area].
AB - To study the seasonal change characteristics and form composition of nitrogen and
phosphorus output concentration and pollutant discharge load with rainfall
characteristics at the outlet of Gufu river small watershed,the quality and
quantity of water combined with natural rainfall events were monitored from
January to December 2014.The results showed that the annual runoff volume of the
Gufu river small watershed was 0.6*108 m3.The runoff was concentrated in raining
season (from July to September),accounting for 63.9%.There was significant
(P<0.01) positive correlation between the runoff flow and the annual rainfall.The
annual emission of total nitrogen (TN) was 1432 t.a-1,and the emission was 853
t.a-1 during the raining season,accounting for 59.6% of annual TN emission
content.The dissolved nitrogen was the main form of nitrogen emission,and the
emission load of each month accounted for 55.4%-91.3% of TN.The positive
correlation between the nitrate nitrogen concentration and rainfall was
significant (P<0.05).The annual emission of total phosphorus (TP) was 563.1 t.a
1,and the content during the raining season accounted for 78.6% of TP annual
emission content.The particle phosphorus (PP) was the main form of phosphorus
emission,and the emission load of each month accounted for 41.9%-79.5% of
TP.There was significant (P<0.01) positive correlation between the annual
rainfall,sediment and TP,PP.The correlation between the total dissolved
phosphorus concentration and rainfall was significant (P<0.05).
PMID- 29965041
TI - [Characteristics of Nitrogen Transport and Its Source Trace in Loess Plateau's
Dam Watershed in Alternating Wet and Dry Seasons:A Case Study of Yangjuangou
Watershed].
AB - In this study,we wanted to explore the impacts of N wet deposition on N export
and trace the N source by isotopic method through monitoring N wet deposition in
Loess Plateau's Dam Watershed in alternating wet and dry seasons,through
measuring N wet deposition,rainfall-runoff and base flow process and analyzing
concentration change of different forms of N.The results showed that there were
11 rainfall events in the 2015 wet season,in which N wet deposition load reached
814.18 kg and N deposition flux was about 4.26 kg.hm-2,while there were three
rainfall events in the 2015 dry season,in which N wet deposition load reached
155.58 kg and N deposition flux was 0.83 kg.hm-2,so it presented a great seasonal
variability.By collecting the dynamic process of four rainfall events,we found
that,different rainfall intensity had different influence on N export process.The
contribution of N wet deposition of four rainfall events to N export in watershed
was 16.94 kg.The ratio that N output load of rainfall and river in watershed N
output load was 14.45%-64.84%,which showed that the contribution of rainfall to
watershed N transport was big.The variation range of delta15 N in Loess Plateau's
Dam Watershed was big,which was -0.8440/00-12.7910/00,and the delta18 O was
within the range of 8.166 0/00-15.115 0/00 in the dam watershed.
PMID- 29965042
TI - [Comparison of Nitrogen and Phosphorus Uptake and Water Purification Ability of
Five Submerged Macrophytes].
AB - Uptake of nitrogen (N) and phosphorus (P) and their purification capacity for
five native submerged macrophytes were investigated in laboratory simulated
hydrostatic conditions,including Hydrilla verticillata,Vallisneria
natans,Ceratophyllum demersum,Myriophyllum spicatum,Potamogeton maackianus.The
results indicated that the moisture contents of different submerged macrophytes
were almost the same before and after the test,with the range of 89.8%-92.0%.The
net accumulated biomass changed from 1.52 g.m-2 to 12.92 g.m-2 among different
submerged macrophytes,and the highest net accumulated biomass of Hydrilla
verticillata was 8.5 times higher than the lowest plant of Potamogeton
maackianus.The N and P contents of five submerged macrophytes ranged from 26.54
to 34.44g.kg-1 and from 2.54 to 4.01g.kg-1,respectively,and the N and P contents
of Ceratophyllum demersum were relatively high.Total N and P removal efficiency
of different submerged macrophyte treatments had ranges of 63.8%-83.1% and 49.2%
70.8%,significantly higher than those of the CK treatment (39.9% and
36.9%),respectively,and the removal efficiency decreased in the order of Hydrilla
verticillata >Ceratophyllum demersum >Vallisneria natans >Myriophyllum spicatum
>Potamogeton maackianus.Total N and P removal efficiencies of different submerged
macrophyte treatments were significantly correlated with net accumulated
biomass,with correlation coefficients of 0.994(P<0.01) and 0.996(P<0.01).The
contribution of direct N and P uptake to different submerged macrophytes had the
ranges of 1.5%-13.3% and 2.2%-13.2%,and the synergism contribution (deducting
self-purification capacity of water) of different submerged macrophytes ranged
22.5%-29.9% and 10.1%-20.6%,indicating that the synergistic effect of submerged
macrophytes purification was much more significant than the direct uptake effect
in the process of water purification.
PMID- 29965043
TI - [Pollution Level, Distribution Characteristics and Risk Assessment of 32 PPCPs in
Surface Water of Luomahu Lake].
AB - A total of 22 water samples collected from Luomahu Lake were determined using
high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) to
evaluate the pollution level,spatial distribution and ecological risk of 32
PPCPs.23 PPCPs were detected in surface water of Luomahu Lake and the total
concentrations of 22 samples were 892-1536 ng.L-1.The concentration of
norfloxacin (256-707 ng.L-1) was the highest among the detected PPCPs,followed by
ketoprofen (85-438 ng.L-1),acesulfame (101-290 ng.L-1) and naproxen (1.9-112 ng.L
1).Spatial differences were found in concentrations of PPCPs in various sampling
sites.Concentrations of PPCPs in northeast of Luomahu Lake were higher than those
of southwest.Concentration of PPCPs in Fangtinghe River was high and that of
Zhangshanzha River was relatively low.The risk assessment of 13 pharmaceutical
PPCPs showed that risk quotients (RQs) of norfloxacin were 0.26-0.72,posing
medial risk to aquatic ecosystem.Gemifibrozil posed low ecological risks with
RQs>0.01 in most sampling sites.RQs of other 11 PPCPs were less than 0.01,posing
no ecological risks.The combined risk quotients of 12 PPCPs in water of Luomahu
Lake were 0.29-0.75,indicating that those compounds posed an medial risk to
aquatic ecosystem.Human health risk assessment showed that the RQs were less than
one for 6 selected PPCPs,indicating that these compounds did not appear to pose
an appreciable risk to human health by potential environmental exposure from
drinking water.
PMID- 29965045
TI - [Effects of pH and Complexing Agents on Sb(V) Adsorption onto Birnessite and
Ferrihydrite Surface].
AB - Effects of pH and complexing agents on Sb (V) adsorption onto birnessite and
ferrihydrite surface were investigated.The results indicated that birnessite and
ferrihydrite had strong ability to adsorb Sb (V).The removal efficiencies of Sb
(V) by birnessite and ferrihydrite were dependent on the initial pH in
solution.The removal efficiency of Sb (V) increased with the decrease of solution
pH.At pH 5.0,the removal efficiencies,adsorption rate and adsorption capacity
were better than those at pH 7.0 or 9.0.The adsorption process of Sb (V) on
birnessite and ferrihydrite could be well described by the pseudo-second-order
model.The Langmuir model best described the adsorption behavior of Sb (V) by
birnessite and ferrihydrite at pH 5.0.The presence of citric acid or EDTA had
significant effect on Sb (V) adsorption onto birnessite and ferrihydrite.
PMID- 29965044
TI - [Distribution, Sources and Risk Assessment of the PAHs in the Surface Sediments
and Water from the Daye Lake].
AB - 8 surface sediments and 8 water samples were collected from the Daye Lake in
August 2015.The 16 kinds of EPA control polycyclic aromatic hydrocarbons (PAHs)
were analyzed by GC-MS.The results showed that the PAHs concentrations of surface
sediments and water ranged from 35.94 ng.g-1 to 2032.73 ng.g-1 and from 27.94
ng.L-1 to 242.95 ng.L-1,with average contents of 940.61 ng.g-1 and 107.77ng.L
1,respectively.The distribution of PAHs in surface sediments indicated that the
contents in the center samples were higher than those in the bank samples,but the
water showed nearly the opposite tendency.The 4-5 rings high molecular weight
PAHs were the main components in the surface sediments,and the 2,4 and 5 rings
PAHs were given priority in water.Compared with the other domestic and oversea
lakes,the PAHs pollution of the Daye Lake was at a moderate level.Source
apportionment showed that the PAHs in surface sediments and water from the Daye
Lake came from the combustion source,HWM-PAHs were the dominant part of the PAHs
in the sediment,reflecting the sediment PAHs pollution under the effects of
mining and smelting over a long period;All monomer PAHs and total PAHs content in
sediment did not exceed the ERM and FEL limiting values,showing that there was no
particularly serious ecological risk caused by PAHs in the surface sediments from
the Daye Lake;the incremental lifetime cancer risks assessment showed that the
uptake risk of PAHs in Daye Lake water through the ingestion and dermal
absorption were both in the acceptable range recommended by the USEPA,but all
sites had higher risk than the acceptable risk level recommended by the Sweden
environmental protection agency and Royal society.The pollution of seven
carcinogenic PAHs needs prevention and control.
PMID- 29965046
TI - [Effects of UV Radiation on the Coagulation Process of Kaolin and Involved
Mechanisms].
AB - Kaolin commonly exists in water,and it has an important impact on the water
treatment processes and contaminants'migration and transformation.In this
study,PAC was used as flocculating agent to systematically investigate the
effects of UV radiation on the coagulation process of kaolin by jar test.The
results showed that under neutral and acidic conditions,UV radiation could
promote the coagulation process of kaolin suspension.When the solution
pH,coagulant dosage and irradiation time were 7.0,30 mg.L-1 and 2.0
h,respectively,the kaolin remove rate of effluent after coagulation increased
from 81.05% to 93.90% by using UV radiation.This might be related to the decrease
of-OH stretching vibration absorption peak and the enhancement of Si-O stretching
vibration absorption peak and Si-O bending vibration absorption peak after UV
radiation,so that the number of the active spot (-OH) on kaolin surface
declined.These changes might lead to decrease of the negative charge on kaolin
surface,which promoted kaolin suspension to precipitate in coagulation
process.However,under alkaline conditions,its settlement performance was slightly
lower than the water samples without ultraviolet radiation treatment.
PMID- 29965047
TI - [Effect of Dissolved Humic Acid on Thyroid Receptor Antagonistic Activity of Zinc
in Aquatic Environment].
AB - A rapid recombinant human thyroid (hTR) gene yeast bioassay was used to evaluate
the effect of dissolved humic acid on thyroid receptor antagonistic activity of
ZnCl2.The concentration of bio-available zinc after its reaction with dissolved
humic acids was measured by anodic stripping voltammetry (ASV).Furthermore,the
reaction mechanism of humic acid and zinc was investigated by three-dimensional
excitation-emission matrix fluorescence spectroscopy (3DEEM).The results revealed
that ZnCl2 demonstrated strong thyroid receptor antagonistic activity,and the
concentration inhibiting 20% of the maximum effect of ZnCl2 was 1.70*10-5 mol.L
1.The thyroid receptor antagonistic activity of ZnCl2 was reduced by 30%-50%
after the reaction of dissolved humic acids.The results of ASV showed that the
concentration of bio-available zinc was decreased after the reaction of dissolved
humic acids,the result was similar to that of bioassay test.The thyroid receptor
antagonistic activity of the mixed solution of humic acid and ZnCl2 was increased
after UV radiation treatment,however it was still lower than the antagonistic
activity induced by ZnCl2.The results of 3DEEM showed that ZnCl2 could reduce the
fluorescence peak intensity of humic acid,which could intuitively characterize
the interaction between humic acid and ZnCl2.The above results can provide basic
data and theoretical support for zinc toxicity study in aquatic environment and
the establishment of water quality criteria for znic.
PMID- 29965048
TI - [Optimization and Validation of the Analytical Method to Detect Common Illicit
Drugs in Wastewater].
AB - Illicit drugs have been recognized as a group of emerging pollutants.Based on
previous research,procedures to pre-treat wastewater including SPE column,pH of
water samples,and processes of washing,acidifying and re-dissolving were
compared.It was found that the best recovery was achieved when wastewater was
adjusted to pH=2 and Oasis MCX column was used.It was not necessary to flush the
loaded column or to acidify the eluate prior to evaporation using nitrogen
steam.After evaporation,it is recommended to redissolve the evaporated samples
using 200 MUL acetonitrile and 100 MUL acetonitrile+100 MUL 5 mmol.L-1 ammonium
acetate in Milli-Q water for HILIC-UPLC-MS/MS and C18-UPLC
MS/MS,respectively.After comparing retention times,limit of detection,limit of
quantification,recoveries,and matrix effects of HILIC and C18 methods,C18-UPLC
MS/MS was chosen.Influent and effluent samples from 12 wastewater treatment
plants in Beijing were analyzed using the optimized method for validation.The
validated methods set a firm foundation to apply the sewage-based epidemiology to
monitor illicit drug abuse in China.
PMID- 29965049
TI - [Cathode Electric Field Enhanced Removal of Nitrobenzene from Aqueous Solution
Based on Activated Carbon Fibers (ACF)-Ozone Technique].
AB - Through the environmental factors impact experiments,such as current
intensity,initial pH value of the reaction solution,and the type and
concentration of the electrolyte,effect and mechanism of electrochemically
enhanced removal of nitrobenzene from aqueous solution on activated carbon fibers
(ACF)-ozone technique were studied.The result showed that compared with the ACF
O3 system,the removal efficiency of NB in electrochemically enhanced ACF-O3
system was significantly improved.The effect of current intensity on the NB
removal efficiency in the electrochemically enhanced ACF-O3 system was not
significant.O3 concentration had some effect on the NB removal efficiency.The pH
value of the initial reaction solution had a great influence on the catalytic
activity of ACF in ACF-O3 system.The presence of inorganic salts such as sodium
sulfate,sodium nitrate and sodium chloride inhibited the catalytic ability of ACF
in O3 system.In addition,ACF was destroyed by ozone and the promoting effect of
ACF was reduced.When the cathode electric field was applied on the surface of
ACF,the removal effect of the organic compounds by ACF-O3 was improved
significantly and the structure of ACF was not destroyed by ozone.
PMID- 29965050
TI - [Effect of PVDF Hollow Fiber Ultrafiltration Membranes Modification with
Carbonnanotube on Membrane Fouling Control During Ultrafiltration of Sewage
Effluent].
AB - The modification of hollow fiber ultrafiltration membranes with carbon nanotube
(CNTs) on fouling control was investigated.Considering the antifouling ability of
the CNT-modified membranes and the stability of CNTs layer,several factors were
analyzed and evaluated,including the concentration of ethanol-dispersion,the
diameter of CNTs,and the loading mass of CNTs.Besides,DOC,UV254,and fluorescence
characteristics of the permeate from the CNT-modified membrane were analyzed.The
results revealed that the optimal modification method included a 50%(volume
fraction) ethanol-dispersion,a 30-50 nm diameter-CNTs,and 3 g.m-2 CNTs'
loading.Compared with the virgin membrane,the removal rates of DOC and UV254 by
the CNT-modified membrane were increased by 37% and 56%,respectively.Meanwhile,it
was proved that the humic-like and protein-like materials were more easily
removed by the CNT-modified membrane.
PMID- 29965051
TI - [Enhanced Treatment of Petrochemical Secondary Effluent by Biological Aerated
Filter (Fe2+)-Ozonation Process].
AB - Two parallel biological aerated filters (BAF)-ozonation,named as number 1(feeding
with FeSO4.7H2O) and number 2,were used to treat petrochemical secondary
effluent.The effect of FeSO4.7H2O on COD and phosphorus removal by BAF-ozonation
was studied.Molecular weight distribution,three-dimensional fluorescence scan and
gas chromatography-mass spectrometry (GC-MS) were used to analyze water quality
before and after BAF-ozonation.The results showed the average COD and TP
concentrations were 82.91 mg.L-1 and 1.37 mg.L-1,respectively.When the dosage of
FeSO4.7H2O was 9 mg.L-1,the average removal rates of COD and TP were 52.20% and
71.50%,respectively.The average COD removal rate in number 1 combined process was
17.15%,which was higher than that in number 2 combined process.The TP removal
rate in number 1 combined process was increased by 51.81%.The percentage of
dissolved organic matters with relative molecular weight less than 1*103 was 52%
in the raw wastewater.However,the percentage increased to 75% when treated by
number 1 combined process and the removal rate of various molecular weight
organics was increased.Three-dimensional fluorescence analysis showed that the
dosage of FeSO4.7H2O could improve the removal of fluorescent substances.GC-MS
results showed that the number and concentration of organics were reduced after
number 1 combined process in comparison with number 2 combined process.BAF-ozone
could be enhanced by FeSO4.7H2O when treating petrochemical secondary effluent.
PMID- 29965052
TI - [Specificity of Intact Ladderane Lipids in Anaerobic Ammonium Oxidizing Bacteria
from Four Reactors].
AB - Intact ladderane lipids are a special kind of phospholipids in the anammoxosome
membrane of AnAOB.Phospholipid organic mixture was extracted respectively from
four sludge samples in anaerobic EGSB reactor,aerobic SBR reactor,autotrophic
nitrogen removal SBBR reactor and anaerobic ammonium oxidation EGSB
reactor.Phospholipid extracts of sludge were detected by the HPLC-ESI-MS/MS
method to determine the types of intact ladderane lipids,and the specificity of
intact ladderane lipids was also analyzed,at the same time,the bacterial
community structure of autotrophic nitrogen removal SBBR reactor and anaerobic
ammonium oxidation EGSB reactor was determined by high-throughput sequencing
technology.Analytical results of intact ladderane lipids showed that intact
ladderane lipids were not detected from anaerobic EGSB reactor and aerobic SBR
reactor,and were detected from autotrophic nitrogen removal SBBR reactor and
anaerobic ammonium oxidation EGSB reactor.Five kinds of intact ladderane lipids
were detected in the phospholipid extract of sludge from autotrophic nitrogen
removal SBBR reactor,and seven kinds of intact ladderane lipids were detected in
the phospholipid extract of sludge from anaerobic ammonium oxidation EGSB
reactor.The results of high-throughput sequencing confirmed that the autotrophic
nitrogen SBBR reactor contained AnAOB of the genera Candidatus Brocadia and
Candidatus Jettenia,and the anaerobic ammonium oxidation EGSB reactor contained
AnAOB of the genera Candidatus Kuenenia and Candidatus Jettenia.These results
illustrated that intact ladderane lipids were the peculiar phospholipids in
AnAOB.
PMID- 29965053
TI - [Characteristics of Perchlorate Reduction and Analysis of Consortium Structure in
a Sulfur-Based Reactor at a High Perchlorate Concentration].
AB - The effects of perchlorate concentration and hydraulic retention time (HRT) on
perchlorate reduction characteristics were investigated in a sulfur-based
perchlorate reduction reactor.The results showed that the perchlorate was
completely removed at HRT of 12 h and the influent perchlorate concentration
ranged from 50 mg.L-1 to 194 mg.L-1;The perchlorate removal efficiency was 74% at
HRT of 4 h and the influent perchlorate concentration was 194 mg.L-1;The yield of
sulfate was increased by increasing the influent perchlorate concentration and
HRT;The influent pH and alkalinity was approximately 8.0 and 500 mg.L-1 CaCO3,and
the effluent pH and alkalinity was approximately 6.7 and 100 mg.L-1
CaCO3,respectively;The oxidation reduction potential (ORP) ranged from -380 mV to
-330 mV at the bottom of the reactor,however,ORP ranged from -300 mV to -250 mV
at the top of the reactor;The molecular biological analysis showed that the
microbial consortium structure was different along the flow path in the
reactor,Sulfurovum which is known to oxidize sulfur was decreased from 57.78% to
32.19% and Hydrogenophilaceae which is known to oxidize hydrogen sulfide was
increased from 4.35% to 22.24%.
PMID- 29965054
TI - [Fast Start-up of SBAF System Assisted CANON Process and the Microbial Analysis].
AB - Long period start-up is one of the main restraining factors of the single-stage
completely autotrophic nitrogen removal over nitrite (CANON) process.This study
investigated the fast start-up of the CANON process initiated by a submerged
biological aerated filter (SBAF) method.With conventional activated sludge from
the secondary sedimentation tank of municipal waste water treatment plants as the
seed sludge,the CANON process was successfully started up after the acclimation
of sludge microorganisms for 48 days under the experimental conditions of (30+/
2)C,organic carbon free and controlled dissolved oxygen (stage I:0.3-0.5mg.L
1;stage II-IV:0.1-0.2mg.L-1),with the maximum removal rates of ammonia nitrogen
and total nitrogen achieved at 99.9% and 86.5%,respectively.The population
structure characteristics of microorganisms in the system were studied using high
throughput sequencing of 16S rDNA amplicon.The results demonstrated that the two
dominant microbial strains in the system were Proteobacteria and
Planctomycetes,accounting for 26.6% and 17.8%,respectively.The major contributors
of nitrogen removal were Nitrosomonas in beta-Proteobacteria and Candidatus
brocadia in Brocadiae.Through the above experiments,it was revealed that the
investigated SBAF based CANON possesses had the advantages of fast start
up,efficient biological nitrogen removal and stable operation process.
PMID- 29965055
TI - [Mechanism for Effects of High Free Ammonia Loadings on Biological
Nitrification].
AB - Wastewater treatment plants treating industrial wastewater and municipal
wastewater may suffer from unexpected shock loads of high ammonia
concentrations,which can lead to inhibition of biological nitrification and
failure to meet the wastewater discharge standards.In order to solve the problem
of failure to meet the standards,the effects of high loadings of free ammonia
(FA) on the nitrification process were investigated in this work using a
sequencing batch reactor (SBR).For such purpose,maximum specific degradation
rates of ammonia,maximum specific formation rates of nitrate,specific oxygen
uptake rates and abundances of nitrifying bacteria were monitored.The results
showed that FA promoted nitrification activities at low concentrations and
inhibited the activities when the FA concentration exceeded a certain value.In
addition,high loading concentrations of FA resulted in long recovery times.When
the FA concentration increased from 3.6 mg.L-1 to 8.1 mg.L-1,the abundances of
ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) increased
slightly,as shown by the fluorescence in situ hybridization tests.However,there
were apparent decreases in the abundances of AOB and NOB when the concentration
of FA was higher than 8.1 mg.L-1.The critical FA inhibitory concentrations for
AOB and NOB were 8.1 mg.L-1 and 6.6 mg.L-1.It was found that the NOB flora were
more sensitive than AOB to FA inhibition.
PMID- 29965056
TI - [Impact of Biodegradable Organic Matter on the Functional Microbe Activities in
Partial Nitrification Granules].
AB - To explore the short-term impact of biodegradable organic matter on the
activities of different functional microbes in autotrophic partial nitrification
granular sludge (PNG),the variations of both nitrogen transformation performance
and dissolved oxygen (DO) uptake of PNG were investigated in this study,by
carrying out successive batch tests with and without the organics stressing.The
results showed that the higher the C/N ratio,the lower the specific nitrite
accumulation rate of q(NO2--N).Meanwhile,the increase of heterotrophic bacteria
(HeB) activities caused the fast DO uptake by PNG,which could effectively
suppress nitrite oxidizing bacteria (NOB) with the low oxygen affinity.When
inorganic substrate culture was employed in the following phase,both HeB and NOB
showed low activities,with significant increase in q(NO2--N).In short,the adverse
effects of biodegradable organic matter on the performance of PNG system were
partially reversible,which could benefit to enhance the advantage of ammonium
oxidizing bacteria (AOB) and improve the stability of partial nitrification
reaction.
PMID- 29965057
TI - [Process of Enrichment and Culture of PAOs on a Novel Biofilm Process of
Dephosphorization].
AB - Using the hanging nylon as a biological carrier,a novel biofilm reactor was
adopted to treat synthetic wastewater,and the feasibility of cultivating and
enriching a high concentration of PAOs on this conventional biofilm within a
short time was investigated,which was proved from the aspects of reactor's
operational efficiency,the rate of phosphorus removal and the condition of PAOs
enrichment.After 10d of operation,the rate of orthophosphate removal was higher
than 95% in aerobic phase and the concentration of effluent COD was 50 mg.L-1 or
less in the reactor,which was operated steadily for 50 d at this treatment
level;after 48 d of operation,the reactor's phosphorus uptake rate and release
rate were increased from 3.4 mg.(L.h)-1 and 3.4 mg.(L.h)-1to 8 mg.(L.h)-1 and 6
mg.(L.h)-1,respectively,and the aerobic and anaerobic cycles were shortened from
equally 6 h to 2 h and 3 h,respectively.The fluorescence in situ hybridization
(FISH) test found that the PAOs' abundance was increased from the original 48.96%
to 70% on the 50th day,meanwhile the PAOs showed reunite chunk state in hybrid
figure,the thickness of biofilm measured by direct microscopic process was about
28.9 MUm,which all proved that the PAOs in biofilm were at the end of the growth
kinetics and the biofilm was mature.By hardening culture for 50d,a high
concentration of 70% in full organisms of PAOs could be enriched in the
conventional nylon filler,enabling the reactor to show a high efficiency in
removal of phosphorus and organic matter from sewage.
PMID- 29965058
TI - [Identification of Efficient Strain Applied to Mining Rehabilitation and Its Rock
Corrosion Mechanism:Based on Boosted Regression Tree Analysis].
AB - The soil and water loss problem in rock mining areas is an extremely serious
problem,and microbes play significant roles in ecological restoration of those
areas.In this study,directive screening was used to explore the efficiency of
microbe-mediated habitat restoration and the underlying mechanisms.A bacterial
strain NLX-4,which was then identified as Pseudomonas protegens according to its
16S rRNA gene sequence,was screened out as an efficient silicate dissolution
bacterium with the ability to secrete siderophore and indole-3-acetic acid
(IAA).Moreover,pH value,element (K,Al,Si) release,organic acid content,amino acid
concentration,polysaccharide content,and rock particle diameter variation in
culture medium were analyzed to explore the ability of P.protegens NLX-4 to
promote dolomite dissolution under controlled experimental conditions.These
results showed that P.protegens NLX-4 could play a positive role in dolomite
dissolution by producing tartaric acid (>777 mg.L-1) and polysaccharides
(>8.21g.L-1).Therefore,P.protegens NLX-4 is an efficient microbial resource that
can be used in rehabilitation of abandoned mines and has great application
potential.
PMID- 29965059
TI - [Effect of Cadmium on Biodegradation of Nonylphenol by Pseudomonas aeruginosa].
AB - The influence of Cd on the degradation of nonylphenol (NP) by P.aeruginosa SH1
was investigated in this study.The investigation revealed that biomass of the
strain was significantly declined with the increase of Cd2+ concentration.The
biomass was declined by 27.1% in the presence of 10 mg.L-1Cd2+ after 24 h.The
addition of Cd2+ had a great influence on adsorption of NP by the strain.As for
the effect of living stain,adsorption by P.aeruginosa SH1 cells was stimulated at
low concentrations of Cd2+(0.5 mg.L-1),while inhibited at higher levels (>=5 mg.L
1).As for inactivation of microbes,adsorption by cells was stimulated at higher
concentrations,but was only slightly influenced at low levels.The results showed
that the intracellular enzymes had much greater degradation rate than the living
cells.Different concentrations of Cd2+ had different effects on bacteria and
intracellular enzyme degradation of NP separately.The degradation efficiency when
using intracellular enzymes and bacteria was inhibited at higher levels of Cd2+
and the intracellular enzyme inhibition was more significant.Degradation by cells
was stimulated at low concentrations of Cd2+,but no significant impact was found
on that by intracellular enzymes.The degradation process of NP by intracellular
enzymes of the strain conformed to the first-order kinetic model.The highest
reaction rate was achieved when the concentrations of Cd2+ was 0.5 mg.L-1 and the
half-life of this substrate was 5.5 h.However,the degradation process of NP by
the strain did not conform to the first-order kinetic model.
PMID- 29965060
TI - [Effects of Different Agricultural Practices on Soil Carbon Pool in North China
Plain].
AB - North China Plain is an important region of grain production.Soil fertility and
grain production in this region are significantly influenced by the levels of
soil carbon and nitrogen.In order to explore the effects of agricultural
practices on the levels of soil carbon and nitrogen,a long-term field experiment
was started in 1999 in Quzhou County,Hebei Province.Four treatments,including
following nature (F),tillage without straw (N),no tillage with crushed straw
incorporation (S),and tillage with crushed straw incorporation (TS),were chosen
to collect soil samples at the layers of 0-20 cm and 20-40 cm in 2013.Soil
organic carbon (SOC),soil inorganic carbon (SIC),total carbon (TC),total nitrogen
(TN),delta13CSOC,delta13CSIC and delta15 N were analyzed.The results indicated
that compared with F,SOC stocks of N,S and TS decreased by 21.6%,12.3% and 3.4%
in the 0-20 cm soil layer,but the changes of SIC stocks were not significant.In
the 20-40 cm soil layer,the changes of the SOC stocks were not significant,but
the SIC stocks increased by 4.1%(N),7.3%(S) and 5.0%(TS) compared to
F,respectively.Major contribution of SIC increase was the pedogenic inorganic
carbonate (PIC),which increased by 97%-261% in the farmland soil.In the soil
layer of 0-20 cm,the values of delta15N,delta13CSIC and delta13CSOC in the
farmland treatments were higher than those of F,meanwhile,the values of delta13
CSOC were significantly higher than that of F.In the soil layer of 20-40 cm,the
values of delta15N and delta13CSIC were lower than those of F,but the value of
delta13CSOC showed the opposite trend.In North China Plain,lithogenic inorganic
carbonate (LIC) of farmland soil decomposed and PIC increased by the soil-crop
system,which provided CO2 for the formation of PIC,and straw returning was an
effective agricultural practice to restore the soil carbon decreased by
tillage.There should be more long-term monitoring and studies for the impacts of
crop straw incorporation and tillage on SOC and SIC,especially for soil in deeper
layers.
PMID- 29965061
TI - [Seasonal Variations of Soil Microbial PLFAs and Soil Enzyme Activity Under the
Citrus Plantation in Mt. Jinyun, Chongqing].
AB - The soil microbial community and soil enzyme activity are important parts of soil
ecosystem,and they are sensitive to the ecological environment.In this
study,citrus plantation in Mt.Jinyun was chosen as the research object.The
phospholipid fatty acid (PLFAs) combined with principal component analysis method
was used to study the effect of season changes on soil microbial
quantity,community structure characteristics and soil enzyme activity at 0-20 cm
soil layer under citrus forest.The results obtained from this study were as
follows:1 The season changes had a significant impact on soil microbes
(P<0.05).Moreover,16:0,i17:0,16:1 2OH,18:0,cy19:0omega8c,i17:1omega9c or 16:0 10
methyl were found to be common in all four seasons,and the proportion of each
phospholipid fatty acid was 49.57%,41.63%,35.41% and 38.05%,respectively.In
various microbial species,the PLFAs content of bacteria was the highest,followed
by fungi,and that of actinomycetes was the lowest.Our results revealed that all
kinds of micro-organisms showed obvious seasonal variation characteristics.The
total PLFAs quantity of citrus forest ranged from 6.868 to 24.085 nmol.g-1,which
had a content order of spring >autumn >winter >summer.The PLFAs content of
bacteria,G-,G+ and actinomycetes also showed the same variation trend.However,the
PLFAs content of fungi showed a different variation trend,i.e.,autumn was the
highest,followed by winter and summer,and spring was the lowest.The results
suggested that season change also had a significant impact on microbial community
functional diversity index.The variation trend of richness index (R) followed the
order of spring >winter >autumn >summer.Moreover,the variation trend of diversity
index (H') was winter >autumn >spring >summer.Furthermore,the variation trend of
evenness index (J) was summer >autumn >winter >spring.The dominance index (D)
increased with the change of season.2 Urease showed a change with the seasons
following summer >spring >autumn >winter;Soil invertase,soil catalase and acid
phosphatase activity changed obviously in autumn,followed by spring,summer,and
winter.3 The principal component analysis demonstrated that the PLFAs content of
bacteria,G-,G+,actinomycetes and total PLFAs made the greatest contribution to
soil fertility followed by that of invertase,catalase,acid phosphatase and
fungi.Moreover,our studies showed that the PLFAs content of urease made a minimum
contribution to the soil fertility.
PMID- 29965062
TI - [Composition and Environmental Adaptation of Microbial Community in Shibahe
Copper Tailing in Zhongtiao Mountain in Shanxi].
AB - In order to reveal the effects of heavy metal pollution on microbial community
compositions and microbial community diversity in tailing area,we conducted an
experiment by examining the microbial community in tailing water,sediments and
tailing sand in Shibahe copper tailing in Zhongtiao Mountain.Differences in
microbial community compositions in different habitats and their relationships
with environmental parameters were analyzed.The results showed that the richness
and diversity of microbial community were the largest in tailing sand,but the
lowest in tailing water.Microbial community compositions were similar between
tailing water and sediments.There were significant positive correlations between
the relative abundance of the dominant family (Sphingomonadaceae) and contents of
heavy metals (Cd,Cu,Mn,Ni,Pb,Zn),while there were significant negative
correlations between relative abundances of aulobacteraceae, Methylobacteriaceae,
Nocardioidaceae, Microbacteriaceae, Micrococcaceae, Streptococcaceae and
Paenibacillaceae and heavy metal contents.It showed that most of the bacteria
were inhibited by heavy metals,but Sphingomonadaceae had a higher tolerance to
heavy metals which may indicate that it has a potential for remediation of heavy
metal contamination.
PMID- 29965063
TI - [Spatial Distribution and Source of Perfluorinated Compounds in Urban Soil from
Part of Cities in Anhui Province, China].
AB - In order to explore the spatial distribution and source of perfluorinated
compounds (PFCs),eleven mixed urban soil samples were collected from 7 cities in
Anhui Province in 2013.Fifteen individual PFCs were detected by ultra-performance
liquid chromatography-tandem mass spectrometry (UPLC-MS/MS),and principal
components analysis was used to trace the different sources of PFCs in urban
soil.The results showed that the total concentration of PFCs (SigmaPFCs) ranged
from 1.15 to 5.98 ng.g-1 dry weight (dw),with an average concentration of 2.69
ng.g-1.perfluorooctane sulfonate (PFOS) with a concentration range of n.d.-3.56
ng.g-1 and an average concentration of 0.96 ng.g-1 was the dominant PFC
contaminant,followed by perfluorooctane acid (PFOA) with a concentration range of
n.d.-2.89 ng.g-1 and an average concentration of 0.64 ng.g-1.The highest
SigmaPFCs concentration in all selected mixed urban soil samples was from Chuzhou
City with the value of 5.89 ng.g-1,followed by Jingxian County of Xuancheng City
(4.04 ng.g-1).Interestingly,the PFOS concentration was as high as 3.56 ng.g-1 in
Jingxian County,accounting for 88.1% of the total PFCs concentration,which might
be influenced by paper industry in this area.Comparing to other soil samples in
China,SigmaPFCs concentration of urban soil from Anhui Province was at middle
level.Over 60% of SigmaPFCs in urban soil of Anhui province could be attributed
to the four principal components,represented by PFOA,perfluorobutane
sulfonate,perfluorododecanoic acid,perfluorobutane acid and PFOS.
PMID- 29965064
TI - [Effects of Biochar Pyrolyzed at Varying Temperatures on Soil Organic Carbon and
Its Components:Influence on the Soil Active Organic Carbon].
AB - Soil active organic carbon is the most important carbon pool and a good indicator
in ecosystem management due to its great significance in soil carbon cycling and
soil quality.In order to investigate the effect of biochar (BC) addition on soil
organic matter fractions,apple tree twigs were used to produce BC at 300,400,500
and 600C,respectively.Elemental analysis and Fourier transform infrared (FTIR)
spectroscopy were used to determine the characteristics of BC.Four kinds of BC
were added into soils at five application rates (0,0.5%,1%,2% and 3%) and
incubated at 25C in lab for over 360 days.Soil organic carbon (SOC),microbial
biomass carbon (MBC),water soluble organic carbon (WSOC) and readily oxidized
organic carbon (ROC) were measured during the incubation.The mass fraction of
carbon (C) in the generated BC ranged from 62.20%-80.01%,while hydrogen (H)
ranged from 2.72%-5.18% and Oxygen (O) ranged from 15.98%-30.92%.The increasing
temperature increased the mass fraction of C,while decreased the O and H mass
content,as well as the ratio of H/C and O/C.The addition of BC significantly
increased SOC,and the treatments amended with BC500 had the highest
increments.Compared with the control treatment (CK),the addition of BC produced
at temperatures below 400C increased the contents of MBC,WSOC and ROC during the
incubation,at the end of the incubation,BC300 treatments significantly increased
the contents by 38.25%,82.09% and 63.53%(P<0.05),respectively;BC400 treatments
significantly increased the contents by 26.07%,65.61% and
48.09%(P<0.05),respectively;while lower contents of MBC,WSOC and ROC were found
in the treatments amended with BC produced at temperatures above 400C after 40-60
d incubation.After 360 d of incubation,the contents of MBC,WSOC and ROC were
significantly decreased by 0.27%,13.48% and 14.67% in BC500 treatments and
7.80%,14.66% and 15.79% in BC600 treatments (except for the MBC in BC500
treatment)(P<0.05).The relative contents of ROC ranged from 3.39% to 15.65%,BC
application decreased the relative content of ROC,suggesting that the increase
was in proportion to the stability of organic carbon in the soil.Considering the
content and quality of SOC,when the BC products were applied to the Loutu
soil,500C was the optimal temperature for preparing apple-derived BC due to its
significant increase of the soil organic carbon and a slight decrease of the
relative content of soil active organic carbon.
PMID- 29965065
TI - [Effects of Different Water Managements and Soil Eh on Migration and Accumulation
of Cd in Rice].
AB - A pot experiment was conducted to study the effects of four modes of water
managements on soil Eh values,bioavailability of soil Cd,migration and
accumulation of Cd in rice.These four modes of water managements were moistening
throughout the entire period of rice growth (M),moistening before filling stage
and flooding after filling stage (M-F),flooding before filling stage and
moistening after filling stage (F-M),and flooding throughout the entire period of
rice growth (F).The results indicated that the exchangeable contents of Cd
increased firstly and then declined with the soil Eh values changing from
negative to positive.Compared with M,the other three modes (M-F,F-M,and F)
significantly reduced the contents of Cd in all rice tissues,including
roots,stems,husks and brown rice.Meanwhile,Cd contents in brown rice due to the
treatments of M-F and F were 0.19 mg.kg-1 and 0.10 mg.kg-1,respectively.These Cd
contents were lower than the limits of 0.2 mg.kg-1 in national food safety
standard (GB 2762-2012).Compared with M,the other three modes significantly
decreased Cd accumulation amounts in the aboveground parts of rice and also
decreased Cd translocation factors in rice.There were significant positive
exponential relations between soil Eh values and Cd accumulation amounts in the
aboveground parts of rice,Cd translocation factors in rice,or Cd contents in
brown rice.The rice biomass due to M-F treatment reached the maximum among the
four modes.It was worthy to be mentioned that although Weiyou 46 was considered a
variety rice with high Cd accumulation,Cd content in rice brown of Weiyou 46
could be lower than 0.2 mg.kg-1 in the 5 mg.kg-1 of Cd contaminated soil through
proper water managements.In summary,M-F treatment ensured high rice yield with
low Cd contents in brown rice and could be recommended as the irrigation mode in
rice production.Simultaneously,maintaining soil Eh value between -160--130 mV was
also important after the filling stage.
PMID- 29965066
TI - [Mechanism of Soil Eco-Functional Stability Under Pyrene/Cadmium Simplex and
Combined Pollution Stress].
AB - In current scenario,the soil pollution has become very severe and its effects on
agricultural and ecological security issues cannot be ignored as various
contaminants are discharged into soil.Thus,the soil pollution is exigent and has
to be solved.This research took soil resistance (Rt),resilience (Rl) and
stability (Sb) as evaluation indexes for judging soil quality by exerting
different concentration (concentration ratio) gradient of pyrene (PYR),cadmium
(Cd) and pyrene/cadmium (PYR/Cd) combined pollutants.A sympathetic description
was showed from the aspects of microbial activity,diversity and abundance of soil
ecosystem,and the models were constructed to describe the dose-response
relationship between PYR-Sb and Cd-Rt.The research showed that different types of
pollutants had certain inhibition on soil DOC content.In Cd and PYR simplex
pollution,soil microbial mean biomass and colony number decreased with increasing
concentration of pollutants.In PYR/Cd combined pollution,the ratio of PYR and Cd
had a negative correlation with the decreasing rate of DOC and
resistance,meanwhile Cd had a prominent influence on the above-mentioned
correlations,in other words,the soil with higher concentration of Cd had lower
DOC decrease rate and resistance,and Cd would have dominant inhibition effect on
microorganisms under PYR/Cd combined pollution.In addition,this study found the
significant correlation of cPYR-Sb and cCd-Rt,and built the binomial forecasting
model to describe the dose-response relationship of cPYR-Sb and cCd-Rt.
PMID- 29965067
TI - [Fractions Transformation of Heavy Metals in Compound Contaminated Soil Treated
with Biochar, Montmorillonite and Mixed Addition].
AB - A compound contaminated soil sampled from Lingxiang City,Hunan Province,was used
to investigate the effects of biochar (BC) and montmorillonite (MM) addition on
heavy metals fractions.The addition amounts of BC and MM were
1%,2%,5%,respectively,and the mixture treatment was 1% BC+1% MM.BCR (European
Community Bureau of Reference) sequential extraction method was used to assess
the fractions of heavy metals in soil after incubation.The results indicated that
adding BC alone significantly reduced the available contents of Pb,Cu and
Cd.Among montmorillonite treatments,MM5% treatment decreased the weak acid
extractable content of Cu,Pb,Zn,Cd by 27.6%,19.2%,25.6%,19.2%,respectively.BC+MM
treatment worked well,decreased the weak acid extractable content of Cu,Pb,Zn,Cd
by 15.8%,15.9%,13.1%,12.0%,and increased the residual content by
39.0%,110.1%,9.6%,62.5%,significantly reducing the mobility of the four
elements.For the stabilization effect,MM treatment worked better than BC
treatment,and a combination of two amendments worked the best.
PMID- 29965068
TI - [Screening of the Reduction/Stabilization Reagent for Cr(VI) Contaminated Soil in
a Planting Site and Reaction Process Monitoring].
AB - There are lots of problems in the domestic remediation of Cr (VI) contaminated
soil field,such as lack of the key processing parameters,poor long-term effect
and so on.The Cr (VI) heavy polluted surface soil was sampled from an
electroplating site in North-China,and then treated with five different reducing
reagents.At the same time,the on-line ORP probes and interval sampling test were
chosen to monitor the reaction process,and to explore the reaction rate and
effect.The results showed that No.4 reagent had the highest Cr (VI) reduction
effect,reaching up to 99.5%,and the minimum soil Cr (VI) concentration could
reach 2.4 mg.kg-1.The No.1 and No.4 reagents had relatively faster reducing
rates.There were obvious difference in ORP and pH monitoring values between
different reductants,for example,the No.1 reagent kept the ORP value stable at
around -400 mV.The No.4 reagent gradually increased the value from -200 mV to 100
mV since 30h,and then kept stable.According to the pH difference among different
reductants,the No.4 reagent was the best and kept the pH value at around 7.Taking
together the final effect and process key parameters,the No.4 reagent was the
best.The scale-up experiment was operated with process monitoring,and the ORP and
conductivity values showed that the reduction reaction took about 160 h.This work
would provide theoretical basis for controlling the maintenance condition and
reaction process in soil Cr (VI) remediation.
PMID- 29965069
TI - [Cd(II) Ion Adsorption and Sealing onto SBA-15 Mesoporous Particles and the
Related Potential on Cd(II) Polluted Soil Remediation].
AB - Aiming to expand the utilization of porous silicate minerals in the remediation
of heavy metal contaminated soil,the mesoporous material SBA-15 was successfully
synthesized by using sodium silicate as silica source in this study.And the
obtained SBA-15 samples were characterized by TEM,X-ray diffraction,N2 adsorption
desorption and FTIR.Furthermore,characterization of Cd (II) adsorption and
sealing performance onto SBA-15 were evaluated through batch experiment,and the
remediation potential of Cd (II) contaminated soil was investigated by brassica
planting in a pot experiment.The results showed that SBA-15 had the mesoporous
structure with surface area of 507.3 m2.g-1 and pore size of 7.38 nm.The maximum
Cd (II) adsorption capacity was 76.43 mg.g-1 at pH above 7.0 with the adsorption
isotherm fitting the Langmuir model in the solution of 100 mg.L-1 Cd (II).The
increase in ionic strength reduced the Cd (II) adsorption capacity.The Cd (II)
loaded SBA-15 could be regenerated with 0.1 mol.L-1 HNO3,while Cd (II) could be
strongly sealed in the pore structure after introduction of sodium silicate into
the system.The pot experiment proved that the addition of SBA-15(4.5 g.kg-1) into
Cd-contaminated soil could reduce Cd (II) availability,enhance the transformation
of soluble and exchangeable Cd (II) fractions into carbonate and Fe-Mn oxides
bounded forms,inhibit the Cd (II) accumulation in the plant tissue and improve
the brassica growth.Based on these results,it can be concluded that combination
of the SBA-15 particle with sodium silicate has great potential to remediate Cd
(II) contaminated soil through adsorption and sealing properties.
PMID- 29965070
TI - [Bioaccumulation of Halogenated Flame Retardants in Fish of Dongjiang River].
AB - Bioaccumulation factor (BAF) plays a key role in identification of
bioaccumulative substance and in assessment of chemical risks.In order to reveal
the bioaccumulation behavior of fish in Dongjiang River,sediment,water and fish
samples were collected from Dongjiang River and PBDEs,DBDPE,DP,TBBPA and HBCDs
were measured.The ranges of lgBAF were 5.0-7.4,6.1-7.1,4.6-7.9,2.6-4.6 and 4.8
7.7,respectively.In the present study,most HFRs had a lgBAF of higher than
3.7,which suggested that they might be bioaccumulative.The BAF values of HFRs
increased with increasing lgKow,when lgKow>7,the bioaccumulation extent decreased
with the increase of lgKow.Biotransformation of gamma-HBCD toward alpha-HBCD and
the metabolism of BDE66 and BDE99 of these isomers might attribute to the
deviation from the general trend predicted by Kow.More attention should be paid
to DBDPE,since its BAF value was higher than that of BDE209.The BSAF values of
most PBDEs,DBDPE,DP,TBBPA and HBCDs congeners in three fish species were less
than 1,indicating that these compounds were unlikely to become a source of
pollution to the aquatic organisms due to the poor bioavailability.
PMID- 29965071
TI - [Characteristics and Evaluation of Heavy Metal Pollution in Vegetables in
Guangzhou].
AB - Vegetable is an indispensible component of human daily diet,and contamination of
vegetables by heavy metals directly threatens human health.In this study,116
vegetable samples were collected from 12 administrative districts of Guangzhou
City for analysis of six heavy metals,Cu,Zn,Pb,Cd,Ni,Cr.A combination of single
factor evaluation and Nemero Index analysis was employed to determine specific
heavy metals exceeding allowable standards and analyze the characteristics of
pollution.Risk of exposure was utilized to assess human health risks originating
from eating locally planted vegetables contaminated by heavy metals.The results
showed that contents of Cu,Zn in the 8 sorts of vegetables were below the
standards of maximum allowable content and the contents of heavy mental Cr of up
to 91.67% vegetable samples were higher than their standard.Lettuce sativa
var.angustana Irish,Luffa acutangula L.,Lycopersicon esculentum Mill.and Daucus
carota L.were the 4 species of Pb exceeding vegetables,with the exceed ratio
reaching up to 35.71% and Daucus carota L.exceeded the target value most
seriously.Only the content of Cd in Lycopersicon esculentum Mill.was over
standard,with the rate of 31.25%.And the highest rate of over-standard of the
content of Ni in 3 species of vegetables,which included Lactuca sativa L.,Ipomoea
aquatica Forsk and Brassica parachinensis,reached 8.33%.For the contamination
level of the eight kinds of vegetable,Lactuca sativa L.,Ipomoea aquatica
Forsk,Brassica parachinensis,Raphanus sativus L.and Daucus carota L.were put into
the class of alarming,while Lettuce sativa var.angustana Irish,Luffa acutangula
L.and Lycopersicon esculentum Mill.were classified as secure.Heavy metals'
comprehensive pollution degree of 4 species of vegetables presented a trend of
leafy vegetables >rootstalk vegetables >stem vegetables >solanaceous
fruits.Health risk assessment showed that Guangzhou citizens eat more frequently
Ipomoea aquatica Forsk and Lactuca sativa L.and Brassica parachinensis were prone
to higher accumulation of heavy metals,and the dietary intake of heavy metal Cr
might cause harm to human health and intake of Cd would bring potential health
risk to the human body.Risk of exposure to heavy metal through oral ingestion of
vegetables was proved to be higher for children than adults.
PMID- 29965072
TI - [Variation Characteristics of Vegetables Cadmium Uptake Factors and Its Relations
to Environmental Factors].
AB - The consumption of vegetables is a probable cause of Cd exposure in several world
areas including China.In this study,we selected the prefecture of
Youxian,southern China,as a case to analyze the influences of various
environmental factors on Cd accumulation in vegetables based on a large scale
agricultural and climatologically survey and collection of 585 irrigation water
and 625 paired soil-vegetables samples.The results showed the concentration of Cd
differed greatly in the irrigation water,soil and vegetables.The average daily
dose for the adult populations consumed vegetables cropping in affected areas was
slightly above the tolerable daily intake level,suggesting a potential health
risk.The vegetables Cd uptake factor followed the natural lognormal
distribution,and had a 10 percentile probability of higher than 1.The PUF values
exhibited comparable results and appeared to define a reasonable and consistent
Cd risk assessment.Many environmental variables (soil pH,soil organic
matter,cation-exchange capacity,rainfall,water pH,and nitrogenous fertilizer
usage) exhibited significant correlations with the concentrations of Cd in the
soil-vegetable system.The canonical corresponding analysis and path model
analysis found that soil pH and soil organic matter (SOM) had major direct
effects on PUF.The close correlations between rainfall,water pH,nitrogen
fertilizer usage and PUF were mainly resuled from the direct effect of soil pH
and SOM.The high field-moisture capacity in the study area generated a rapid
acidification causing the migration of Cd to weaker bounding sites thus promoting
the vegetables uptake.The excessive application of nitrogen fertilizers led to a
substantial loss of SOM and worsening of soil acidification ultimately causing
increasing Cd accumulation in vegetables.Considering that the soil pH and SOM in
the study area were maintained at a low level,the accumulation risk of Cd in soil
vegetable system needs to be addressed.The influence of environmental factors on
vegetables accumulating Cd needs to be fully considered for better and safer
vegetables production.
PMID- 29965073
TI - [Effect of Sewage Sludge Compost Products Application on Total Mercury and
Methylmercury in Soil and Plants].
AB - Two different sludge composting products (with and without biochar) were applied
in field to study the variations of total mercury (THg) and methylmercury (MeHg)
in soil and plants,as well as their migration in the soil-plant system and
accumulation ability in plants during the sludge compost land use process.The
results indicated that the concentrations THg and MeHg in soil increased after
applying sewage sludge compost products,while the THg level was still lower than
the secondary standard of national soil environmental quality.Biochar was
speculated to probably promote the soil mercury methylation with lower MeHg/THg
ratios in different soil treatments.THg concentrations in mature plants were
significantly lower than those in seedling stage,but MeHg levels were higher than
those in seedling stage.An obvious influence of composting on MeHg enrichment in
plants was observed,and this similar effect was not found for THg enrichment.MeHg
concentration in the soils applied with biochar compost was significantly higher
than that without applying biochar compost soil,while MeHg in plant presented a
contrary trend with higher level observed in no-biochar compost soil,suggesting
that the addition of biochar could be in favour of soil MeHg formation and
inhibit the MeHg accumulation in plants by influencing its migration.Since a
strong MeHg accumulation ability with BCF of 1.24-14.63 was present in plant,the
mercury ecological risk in soil environment caused by long-term fertilizing
should be noticed.
PMID- 29965075
TI - [Estimating the Secondary Organic Aerosol Concentration and Source Apportionment
During the Summer and Winter in the Nanjing Industrial District].
AB - Volatile organic compounds (VOCs) were determined by GC5000, an automatic on-line
Gas Chromatography-Flame Ionization Detector. Elemental carbon (EC) and organic
carbon (OC) were determined by the thermal/optical method using DRI-2001A during
the periods of June 15th-July 15th 2015 and December 16th 2015-January 15th 2016.
The concentration of secondary organic aerosol(SOA) was estimated by fractional
aerosol coefficients (FAC) and EC tracer method. The source apportionment relied
on the positive matrix factorization model (PMF). There were several
conclusions:First, aromatic hydrocarbon was the main substance causing the SOA
pollution in the Nanjing Industrial district, the contributions of aromatic
hydrocarbon to SOA during summer and winter were 80.39% and 94.63%, respectively.
The main contributers were benzene, toluene, ethylbenzene, m,p-xylene and o
xylene (BTEX). In the summer, SOA concentration ranged from 5.84-20.88 MUg.m-3
with an average of 12.15 MUg.m-3 and in the winter ranged from 2.17-17.73 MUg.m-3
in which the average concentration was 6.91 MUg.m-3. Secondly, SOA concentration
decreased when wind and precipitation increased. By using the PMF model, a total
of 7sources of SOA were determined in summer and 6 were determined in winter.
There were 3 main sources in summer, including painting, petroleum processing and
petrochemical industry, and the contributions to SOA were 0.65 MUg.m-3, 0.21
MUg.m-3, 0.18 MUg.m-3, respectively. In winter, the most important SOA pollution
was from painting, in which the contribution was 0.94 MUg.m-3.
PMID- 29965074
TI - [Influencing Mechanism and Spatio-temporal Pattern of Stomatal Ozone Flux of
Winter Wheat Under Ozone Pollution].
AB - As one of the main atmospheric pollutants over surface layer,researches on the
increasing surface ozone concentration and its impact on main crops have become
the focus of every government and the public.In this paper,based on the
observations in Nanjing using the main local cultivars in China's major winter
wheat producing areas,it was expected to obtain the data including ozone
concentration,meteorological data and stomatal conductance by continuous
observation.Stomatal conductance model was used and parameterized,combined with
flux model,we analyzed the characteristics of stomatal flux in winter wheat under
ozone pollution.At the same time,the stomatal conductance and stomatal ozone
absorption flux of winter wheat were simulated in Jiangsu Province.The main
results were as follows:Elevated ozone concentration could reduce stomatal
conductance of winter wheat leaf and stomatal conductance decreased with the
increase of ozone concentration.According to the observational data through the
experiment,based on the boundary line technology,stomatal conductance model was
parameterized to simulate stomatal conductance of wheat leaves from environmental
factors.Approximately 90%,77% and 83% variation of measured stomatal conductance
could be explained by the stomatal conductance model.In the experiment,the total
ozone absorption flux in ozone concentration of CK (53.67 nL.L-1),100nL.L
1,150nL.L-1 was 6.42 mmol.m-2,12.27 mmol.m-2,13.90 mmol.m-2 respectively.The
ozone concentration gradually increased from early period to late period during
the period of winter wheat growth in Jiangsu area.The average stomatal
conductance followed the order of the middle stage >the later stage >the early
stage.Winter wheat ozone cumulative absorption flux was the highest during the
middle stage.
PMID- 29965076
TI - [Modeled Deposition of Fine Particles in Human Airway in Northern Suburb of
Nanjing].
AB - The particles number concentrations were determined by Wide-range Particle
Spectrometer (WPS) in northern suburb of Nanjing in January and April 2015. The
information of size distributions was applied in the multiple-path particle
dosimetry model (MPPD) v.3.04 to quantify deposition fractions (DF) and number
concentration (NC) depositions of fine particles in different regions of human
airway, at different air quality levels, at rest and exercise. DF of nucleation
mode and Aitken mode at rest and exercise were similar, while DF of accumulation
mode at exercise was 2.49 times of that at rest. DF of nucleation mode and Aitken
mode in pulmonary (PUL) was the highest, about 48.17% of total deposition
fractions (TDF) at rest and 54.23% of TDF at exercise. DF of accumulation mode in
head was the highest, about 41.23% of TDF at rest and 80.47% of TDF at exercise.
The particle NC deposition in human airway in winter was lower than that in
spring, and the total NC deposition in 3 regions was in the order of PUL >
tracheobronchial(TB) > head. Compared with resting, nucleation mode deposition in
PUL and accumulation mode deposition in TB and head increased at exercise. The
worse the air quality, the higher the deposition growth rate of exercising to
resting in head. DF difference among regions was mainly due to the different
physiological parameters, while NC deposition difference was mainly due to the
different particle NC in the local environment.
PMID- 29965077
TI - [Concentration Characteristics and Influencing Factors of Atmospheric Particulate
Matters in Spring on Weizhou Island, Beihai, Guangxi Province].
AB - To investigate the characteristics of atmospheric environment and possible cross
boundary transports in the north of South China Sea, field experiments were
carried out on Weizhou Island from March to April, 2015. The concentration and
particle size distributions of atmospheric particulate matters were measured, and
the concentration characteristics and the source of particulate matters were
analyzed in combination with meteorological factors and back trajectory analysis.
The results showed that:the PM1, PM2.5 and PM10concentrations were (21+/-12)
MUg.m-3, (35+/-19) MUg.m-3, (43+/-20) MUg.m-3, respectively. The mass
concentrations of PM1, PM1-2.5 and PM2.5-10 accounted for 50%, 32%,18% of PM10
mass concentrations, respectively. Besides, the number concentrations of
particulate matters with particle sizes of 0.5-1 MUm, 1-2.5 MUm and 2.5-20 MUm
accounted for 93.5%, 6.1% and 0.4% of the total number concentration,
respectively. The particle number concentration was negatively correlated with
visibility and air pressure. Backward trajectory analysis showed that air masses
from southwest direction accounted for the highest frequency effect (45.9%), in
this case, particulate matters with particle sizes of 0.5-1 MUm, 1-2.5 MUm and
2.5 MUm had the minimum number concentration and NO had the highest
concentration. Air masses from the east direction accounted for 34.1% of the
frequency effect with the minimum SO2concentration and the highest O3
concentration. The concentrations of NO2, NOx, O3 and CO were the minimum when
air masses came from the south direction which accounted for 12.5% of the
frequency effect. Air masses from the northeast had the lowest frequency effect
(7.4%), but had the maximum particle number concentration, mass concentration and
the concentration of gaseous pollutants except O3 and NO. Atmospheric fine
particles and gaseous pollutants on Weizhou island were affected by transport
from Chinese mainland and Southeast Asia. Pollutants from Chinese mainland were
mainly from industrial sources, while pollutants from Southeast Asia were mainly
from the shipping business inside and outside ports.
PMID- 29965078
TI - [Polycyclic Aromatic Hydrocarbons in the Atmosphere of Dajiuhu, Shennongjia,
China].
AB - The concentration, potential source and health risks of 16 polycyclic aromatic
hydrocarbons (PAHs) in the atmosphere of Dajiuhu, Shennongjia, China, were
studied. Polyurethane foam (PUF) Passive air samplers (PAS) were settled. The
results indicated that the total concentrations of 16 PAHs in different samples
ranged from 6.94 to 184.23 ng.m-3, with the mean of 30.36 ng.m-3. The dominant
compounds were low rings PAHs, such as Phe, Nap, Pyr, Fla, Flu and Ant. Compared
with other regions, the PAHs pollution of Dajiuhu atmosphere was at a low level.
Higher PAHs concentrations were detected in nearby Deer farm, Dajiuhu peat area
and Dajiuhu Wetland Authority. Higher PAHs concentrations were detected in autumn
and winter, whereas lower concentrations were detected in spring and summer.
Potential pollution sources of PAHs were investigated by diagnostic ratios and
backward trajectory analysis, which indicated that coal and biofuel combustion,
vehicle emissions and petroleum were the main sources. PAHs of Dajiuhu in air not
only came from local emission, but also originated from Hubei, Henan and Hunan's
atmosphere transport for most part and long range transport from northwest
direction for small part. Health risks assessment results showed that the annual
average concentration of total Benzo(a)pyrene-equivalent carcinogenic potency
(?BaPeq) was 0.208 ng.m-3, lower than the value recommended by Ambient Air
Quality Standard of China(GB 3095-2012, 1 ng.m-3), indicating a low carcinogenic
risk for the local residents.
PMID- 29965079
TI - [Spatial Distribution Characteristics of NMHCs in Spring in Cangzhou City].
AB - Simultaneous collections of non-methane hydrocarbons (NMHCs) were carried out at
15 sampling sites including urban, suburb and potential pollution areas in
Cangzhou City in spring 2015. The results showed that NMHCs were generally higher
in urban areas than those in suburb and rural areas; the highest concentration of
NMHCs was observed at Cangzhou High-tech zone (urban area); the concentrations of
NMHCs were significantly lower at rural sites than in most urban sites except
Hejian site; vehicular emissions were the main sources of NMHCs in Cangzhou;
Cangzhou chemical fertilizer plant and Cangzhou oil refinery had no significant
influence on urban NMHCs during their shutdown period; Dagang Oilfield, with
better oil and gas recovery systems, did not have a significant impact on urban
NMHCs. In general, alkanes, alkenes and aromatics accounted for 65%, 16% and 19%
of NMHCs in Cangzhou City, respectively; xylene (19%), ethylene (14%),
toluene(11%), propylene (5%), isopentane (5%) and isopentene (5%) were the most
dominant contributors to ozone formation potential; aerosol formation potential
was mainly derived from toluene (28%), pinene (28%), xylene(16%), ethylbenzene
(9%) and benzene (9%).
PMID- 29965080
TI - [Emission Characteristics of Residential Coal Combustion Flue Gas in Beijing].
AB - Honeycomb briquet,biomass briquettes and bituminous coal from suburb of Beijing
were chosen as testing samples to carry out combustion experiments. The
characteristics of inorganic pollutant emission factors and VOCs emission factors
released from the flue gas were studied. The results showed that under the
condition of sufficient combustion, the average emission factors of SO2 from
these three types of coal respectively were 1.50,1.91,1.62 kg.t-1;NOx
0.420,0.901,2.20 kg.t-1;CO 22.4,37.3,87.3 kg.t-1. Combustion emission factors of
gaseous pollutants for NOx and CO were in the order of bituminous coal > biomass
briquettes > honeycomb briquet. SO2 emission factors were in the order of biomass
briquettes > bituminous coal > honeycomb briquet. The 2014 emissions inventory of
the three civil coal combustion pollutants in Beijing was obtained. Bituminous
coal emissions of SO2 was more than 5.5*103 tons,NOx was more than 7.5*103
tons,CO was more than 290*103 tons. All these coal types released more kinds and
higher concentrations of volatile organic compounds in ignition phase and damp
down stage. VOCs emission factor was the highest during ignition phase, followed
by damp down phase.
PMID- 29965081
TI - [Emission Characteristics and Ozone Formation Potential of VOCs from a Municipal
Solid Waste Composting Plant].
AB - In Beijing, the chemical composition and component concentrations of volatile
organic compounds (VOCs) were investigated during the municipal solid waste
composting process using a portable gas chromatograph coupled with a mass
spectrometer. The contributions of VOCs to the ozone formation potential were
computed using the maximum incremental reactivity (MIR) scale and the propylene
equivalent concentration scale. The results showed that the concentrations of
waste discharge in the sorting room, the first fermentation workshop, the second
fermentation workshop, the compost product workshop, and the plant boundary were
10302.1, 15484.1, 929.9, 4693.6 and 370.4 MUg.m-3, respectively. The main VOCs of
the municipal solid waste composting plant were ethanol, limonene, and acetone.
The propylene-equivalent concentrations of waste discharge in the sorting room,
the first fermentation workshop, the second fermentation workshop, the compost
product workshop, and the plant boundary were 25875.7, 4087.9, 378.0, 747.7 and
296.8 MUg.m-3, whereas the O3 formation potentials computed using the MIR scale
were 26979.3, 21168.3, 1469.3, 6439.6 and 455.8 MUg.m-3. Reducing pollution by
controlling the VOCs emission of waste discharge in the sorting room and the
first fermentation workshop is important and can decrease the ozone formation
potential. Given the accuracy and accessibility of the method, the MIR scale is
more suitable for calculating the ozone formation potential of VOCs emitted from
the municipal solid waste composting plant.
PMID- 29965082
TI - [Degradation Characteristics of Composite CVOCs by Non-thermal Plasma].
AB - Non-thermal plasma was used as a pretreatment technology for bio-trickling
filter, employing chlorobenzene and dichloroethane as target pollutants. This
experiment was conducted to study the purification effect and degradation product
in NTP under different frequency power supply,to provide a theoretical basis for
coupling with biotechnology. The results showed that the removal efficiency for
mixed waste gas in the plasma first increased and then decreased with the
increase of the SIE. The maximum energy efficiency was obtained at 6111 J.L-1
under high frequency power and 7167 J.L-1 under low frequency condition,
respectively. Extending residence time caused a rise in mixed gas removal
efficiency, but the removal load didn't always increase and the highest removal
load was observed with the residence time of 5 s, so 5 s was regarded as the
optimal reaction condition for the subsequent analysis in this study. The
degradation products were analyzed under the specific conditions. Experimental
results showed that the amount and the selectivity of carbon dioxide both
increased with the increase of SIE in the plasma reactor. The amount of ozone
increased to a maximum value and then decreased with the increase of SIE in the
plasma reactor, and the amount of ozone produced in low-frequency power plasma
was lower than that in high-frequency power. The trend of TOC values was similar
to the trend of ozone generation, indicating that the best water solubility was
obtained at the highest energy efficiency.
PMID- 29965083
TI - [Chemical Compositions and Source Apportionment of Road Dust in Yuncheng].
AB - Samples of particulate sources in Yuncheng including road dust, salt lake dust,
coal dust, soil dust, construction,cement dust and vehicle exhaust dust were
collected. Elements, ions and carbon species in particulate sources samples were
analyzed. Enrichment factors and potential ecological risk assessment were used
to analyze the characteristics of road dust, and chemical mass balance model was
applied to identify the source of road dust. The results showed that, compared
with other cities, the proportions of Na(12.1970%) and SO42-(8.5971%) were
relatively high while that of Si(9.1123%) was low in road dust in Yuncheng, and
enrichment factors showed that the sources of Pb, Cu, Cr, V, As, Ni, Na and Zn in
road dust were obviously influenced by human activities; the potential ecological
risk of heavy metals in road dust was high, which was affected by anthropogenic
sources such as industrial production, the combustion of fossil fuels and vehicle
exhaust; the profiles of coal dust, vehicle exhaust dust, construction and cement
dust were similar to those of other cities, the Na and SO42- concentrations in
soil dust were relatively high, and the proportions of Na and SO42- in salt lake
dust were 30.3% and 22.7% respectively; salt lake dust was the largest
contributor (53%) to road dust, followed by the soil dust (21%), vehicle exhaust
dust (8%), construction and cement dust (7%), and coal dust (5%).
PMID- 29965084
TI - [Pollution Risk of Heavy Metals in Dust from the Building Along Elevated Road: A
Case Study in Changzhou].
AB - Totally 126 samples of windowsill dust were collected from different floors along
elevated road in Changzhou. The concentrations of Cu, Zn, Pb, Cd, Ni and Cr were
determined, and the vertical distribution and chemical speciation were analyzed.
The enrichment factor, bioaccessiblity, potential ecological risk and health risk
were evaluated. The results showed that the average contents of Cu, Zn, Pb, Cd,
Ni and Cu were 181.95, 709.99, 211.24, 2.76, 101.59 and 257.55 mg.kg-1
respectively, which were all higher than the background value. The enrichment
factor of Cd was 33.05, with enrichment degree of strongly enriched. The
enrichment degrees of Cu, Pb and Zn were all significantly enriched. These four
heavy metals may come not only from transportation source, but also from natural
source and regional industrial polluted gas. The enrichment factors of Ni and Cr
were low, which may result from natural source. With the elevation of house
height, the concentration of Cd increased, the concentrations of Pb and Zn
increased first and then decreased, while Cu showed no significant differences.
Zn, Cd, Cu and Pb mainly existed in the active form, while Ni and Cr mainly
existed in the residual form. The bioaccessiblity of Zn and Cd was high, while
that of other heavy metals was low. The modified potential ecology risk
evaluation results showed that the risk of Cd was extremely high, and contributed
mainly to the potential risk index of multi-element. The Cd from the windowsill
of high height showed higher potential ecological risk. The carcinogenic risk of
Cr to children was higher than the threshold value, while the carcinogenic risk
and non-carcinogenic risk of other metals to children and adults were all below
the safety thresholds.
PMID- 29965085
TI - [Characteristics of Stable Isotope in Precipitation and Its Relationship with
ENSO in Shanghai].
AB - A total of 70 precipitation samples were collected from August 2014 to August
2015 in Shanghai and the oxygen and hydrogen isotope of precipitation were
analyzed. The relationship between the delta18O and deuterium excess of
precipitation and ENSO events was addressed. The results showed that deltaD and
delta18O of precipitation in Shanghai were higher in winter and spring than in
summer and fall. The slope of meteoric water line with these data was a little
smaller than the global meteoric water line. The main reason could be the
unbalanced secondary evaporation in the process of precipitation. The correlation
between the delta18O in precipitation and temperature and precipitation varied in
different time scales. On a seasonal scale, this work revealed that there was no
significant temperature effect in winter, but significant precipitation effect
was found in the annual scales, which was obviously affected by the atmospheric
circulation. delta18O values and deuterium excess in precipitation recorded the
La Nina and El Nino conversion process. During the La Nina event, the delta18O
and d values were more negative than those in the El Nino event.
PMID- 29965086
TI - [Effects of DOC+CDPF on Emission Characteristics of Heavy-duty Diesel Vehicle].
AB - Based on the revolving drum test bench, an experimental study was conducted in
heavy-duty diesel vehicle at China Stage III with and without DOC+CDPF to
investigate the effects of DOC+CDPF on the gaseous and particle emission
characteristics under C-WTVC driving cycle. The results showed that from city
circulation conditions to high way circulation conditions to high-speed
circulation conditions, the CO, THC, CO2 and PM emission factors of the test
vehicle without DOC+CDPF decreased while NOx and PN emission factors increased,
the particle number concentration showed two peaks versus the size of the
particles and accumulated particles predominated. After the test vehicle was
equipped with DOC+CDPF, the emissions factors decreased and the faster the
circulation speed, the greater the decreasing amplitudes of the emissions
factors. Throughout the C-WTVC, the decreasing amplitudes of CO, THC, CO2, and
NOx emission factors were 70.36%, 72.73%, 17.00% and 7.76%, the PM and PN
emission factors decreased by 93.77% and 98.91% respectively. The particle number
concentration still had two peaks versus the size of the particles and the
nuclear mode particles predominated. Besides, the size of the accumulated
particles peak diminished.
PMID- 29965087
TI - [Accumulated Health Risk Assessment of Arsenic in Drinking Water of Major Cities
of China].
AB - Based on the drinking water quality survey data of China's major cities, the
existing disease burden calculation method was improved and disability-adjusted
life years (DALYs) was taken as the end of evaluation to assess the health risk
of arsenic contamination level. The results showed that the concentration of
arsenic in drinking water of major cities in China was very low (0.53 MUg.L-1),
far below the national limit (10 MUg.L-1) and the total lifetime cancer incidence
was 1.76*10-5. The order of risks of different kinds of cancers was:skin cancer
(1.53*10-5) > lung cancer (2.25*10-6) > liver cancer (2.30*10-8) > bladder cancer
(1.34*10-10) and the average disease burden was 1.91*10-6 per person-year. Among
them, skin cancer and lung cancer accounted for 70.2% and 29.0% respectively, and
the disease burdens of bladder cancer and liver cancer were negligible, but the
overall cancer risk was still higher than the recommended level of 10-6 per
person-year by WHO. Although the arsenic level of drinking water in China was not
high, the risk of cancer could not be ignored. Thus more effective and feasible
measures should be taken to reduce arsenic concentration to protect people's
drinking water safety in the future.
PMID- 29965088
TI - [Health Risk Assessment of Microcystins from Drinking Water Source by Monte Carlo
Simulation Method].
AB - To investigate the microcystins(MCs:MC-RR, MC-LR and MC-YR) exposure from
drinking water source and to assess the health risk using Monte Carlo simulation
method. 90 samples randomly collected from five sample points set along the river
were determined using the national standard method (GB/T 20466-2006) during the
period of January to June 2016. Professional risk assessment software@Risk7.0 was
used to evaluate the dietary intake (exposure) risk of MCs based on building a
nonparametric probabilistic evaluation model. First, 90 samples with the MCs were
collected for fitting of distribution and the optimal fitting distribution model
was selected from the results of three statistical test methods:the Chi-Squared
test, the Anderson-Darling test and the Kolmogorov-Smirnov test. Of the 90 water
samples tested, the most frequently detectable MCs was MC-RR with the detectable
rate of up to 51.11% within the content range of 0.0017-0.3863 MUg.L-1, followed
by 47.78% of MC-LR within the range of 0.0285-0.2796 MUg.L-1, and 21.11% of MC-YR
within 0.0030-0.1362 MUg.L-1. These results indicated that vast majority of MCs
in testing samples were at relatively low levels with the highest concentration
of MC-RR at 0.3863 MUg.L-1 and MC-YR concentration was the lowest from drinking
water source. The fit distribution of MC-LR concentration was the
ExtValueMin(0.11391, 0.098462) and that of MC-RR was Logistic(0.058064,
0.053044)(the first number was MU as the position parameter, the second number
was sigma as the scale parameter). The result indicated that health risks of MC
LR from drinking water source were higher than those of MC-RR and MCs pollution
and would lead to high potential health risks especially for children. The health
risks caused by the MC-LR from drinking water source for children were
significantly higher than the maximum allowance levels recommended by USEPA(1*10
4), and the health risks caused by the MC-LR from drinking water source for
adults were significantly higher than the maximum allowance levels recommended by
ICRP(5*10-5). Therefore, it is necessary to strengthen the protection and
monitoring of drinking water source for effective control of water pollution and
protection of human health.
PMID- 29965089
TI - [Potential Risk and Distribution Characteristics of PPCPs in Surface Water and
Sediment from Rivers and Lakes in Beijing, China].
AB - Thirty-four water samples and twenty-three sediment samples from the urban
rivers, ten water samples and five sediment samples from urban lakes were
collected in Beijing. Ten PPCPs (acetaminophen, lincomycin, caffeine,
trimethoprim, azithromycin, sulfamethoxazole, diltiazem, tylosin, carbamazepine,
fluoxetine) were extracted from water samples by solid-phase extraction (SPE) and
from sediment samples by ultrasonic extraction, and then analyzed by high
performance liquid chromatography coupled with tandem mass spectrometry (HPLC
MS/MS). The ranges of geometric mean values were 0-655 ng.L-1 and 0-252 ng.L-1 in
water samples from urban rivers and lakes,respectively. The range of detection
ratio was 0-100% for 10 PPCPs in river water samples, caffeine was the dominant
pollutant in water samples and the detection ratio was 100%, whereas
sulfamethoxazole, diltiazem and tylosin were not detected in river samples. The
range of detection ratio was 0-100% for 10 PPCPs in lake water samples. The
detection ratios of acetaminophen, lincomycin, caffeine and azithromycin were
100%, whereas sulfamethoxazole, diltiazem, tylosin, carbamazepine were not
detected in lake water samples. The ranges of geometric mean values were N.D.
1709 ng.g-1and N.D.-35.9 ng.g-1in sediment samples from urban rivers and lakes,
respectively. The ranges of detection ratio were 4%-96% and 0-100% for 10 PPCPs
in river and lake sediment samples, respectively. The detection ratio of
trimethoprim was 96% and that of tylosin was 4% in river sediment, the detection
ratio of diltiazem was 100% and caffeine, tylosin,carbamazepine were not
detected. The concentrations of PPCPs in water and sediment samples from Yongyin
River, Liangshui River, Tonghui River, Bahe River were higher than those in other
rivers. The concentrations of PPCPs in water and sediment samples from Yongding
River,Kunyu River were lower than those in other rivers. Further risk assessment
results showed that the overall risk was not high in water of rivers and lakes
and the RQ values were below 0.1, which showed low risk to microorganisms. But
the condition was not the same in sediment from rivers and lakes. The RQ values
of acetaminophen were between 0.1 and 1 in sediments from Yongyin River, Tonghui
River, Bahe River. The RQ values of lincomycin were between 0.1 and 1 in
sediments from Yongyin River, Wenyu River,Tonghui River, Hucheng River, Bahe
River, Liangshui River, Houhai Lake. The RQ values of trimethoprim were between
0.1 and 1 in sediments from Yongyin River, Qinghe River, Wenyu River, Tonghui
River Hucheng River, Bahe River, Liangma River, Liangshui River and Houhai Lake.
The RQ values of azithromycin were between 0.1 and 1 in sediments from Liangma
River, Liangshui River, which all showed medium risk to microorganisms in
sediments. The RQ values of azithromycin exceeded 1 from Yongyin River, Qinghe
River, Wenyu River, Tonghui River, Bahe River and Houhai Lake, which showed high
risk to microorganisms in sediments.
PMID- 29965090
TI - [Assessment of the Spatial-temporal Distribution Characteristics and Main
Affecting Factors of Chromophoric Dissolved Organic Matter in Spring and Summer
at the Changjiang Estuary and Adjacent Areas].
AB - The composition and distribution characteristics of chromophoric dissolved
organic matter(CDOM) of Changjiang Estuary and its adjacent waters in spring
(March 2015) and summer (July 2015) were evaluated by excitation-emission matrix
spectroscopy (EEMs) in combination with parallel factor(PARAFAC) analysis. Three
humic-like components[C1(370/495 nm),C2(330/405 nm),C3(365/440 nm)] and one
protein-like component[C4(295/345 nm)] were identified. The distribution patterns
of the four components in spring and summer were almost the same, showing a
decreasing trend from Changjiang Estuary to adjacent waters. In spring, the high
value areas of three humic-like components were located inside of Changjiang
Estuary, and the high value areas of the protein-like component were located in
the South Passage of Changjiang Estuary. In the surface layer, the CDOM was
mainly from terrestrial input and human activities; the influence of terrestrial
weakened in the middle layer because of the lower fluorescence intensity values;
and in the bottom layer the fluorescence values were higher than those in the
middle layer, which was caused by sediment resuspension. There were high value
areas in the Daishan Island, which were related to human activities. In summer,
the high value areas of CDOM were almost the same as those in spring, and all
layers had similar fluorescence intensity values, which indicated that they were
mixed evenly. CDOM in spring and summer had high humification index (HIX) values
in the Changjiang Estuary, whereas for biological index (BIX), its high values
appeared in the adjacent waters. Four components (C1-C4), a355 and DOC, TN, TP,
DO, Chl-a, Salinity were evaluated by redundancy analysis (RDA), which indicated
that C1-C4 and TN, TP were mainly affected by terrestrial input and human
activities, and DOC was affected by terrestrial and marine source together. The
use of EEMs-PARAFAC in combination with multivariate analysis to parse the
composition of CDOM revealed the source of CDOM and main influencing factors in
Changjiang Estuary and adjacent waters, and plays an important role in the
biogeochemical research of biogenic elements in estuarine waters.
PMID- 29965091
TI - [Complexation Between Copper(II) and Colored Dissolved Organic Matter from
Municipal Solid Waste Landfill].
AB - In order to elucidate the evolution mechanism of heavy metal species in landfill
cells, three-dimensional excitation emission matrix fluorescence spectroscopy
(3DEEM), fluorescence quenching titration and parallel factor analysis (PARAFAC)
were employed to study the complexation process between Cu(II) and colored
dissolved organic matter (CDOM) from landfill with different ages. The
experimental results indicated that the landfilled CDOM comprised protein-like,
humic-like and fuvic-like matter. The relative content of protein-like matter
decreased during the landfill process, whereas the humic-like and fuvic-like
matter increased during the process. The range of the conditional stability
constants and the percentage of fluorophores participated the complextion between
Cu(II) and protein-like matter with different ages were 4.00-5.75 and 22.78%
95.30%, respectively. Those parameters changed slightly for humic-like matter
with different ages, which ranged from 4.71 to 5.54 and from 42.35% to 61.46%,
respectively. As regard to fulvic-like matter, those parameters were 4.44-5.25
and 46.14%-57.22%, respectively. The complexation ability of humic-like
substances with Cu(II) decreased during the landfill process, though the
percentage of fluorophores participated the complexation increased. The
complexation ability of humic-like substances with Cu(II) was stronger than that
of fulvic-like matter, though the percentage of fluorophores participated the
complexation in humic-like matter was low compared with fulvic-like matter.
PMID- 29965092
TI - [Effects of Three Bioretention Configurations on Dissolved Nitrogen Removal from
Urban Stormwater].
AB - Multiple chemical forms of nitrogen in urban storm water make its management
challenging. Three types of bioretention systems were constructed in 2015 with
loamy sand as filter media, including a conventional freely drained bioretention
(CB), a modified bioretetion incorporated a submerged zone (MB1), and a modified
bioretention incorporating a submerged zone with woodchips addition (MB2). This
study investigated the role of vegetation, the use of submerged zone and carbon
addition in achieving co-optimized dissolved nitrogen removal in bioretention
systems. Twelve bioretention columns were monitored over a 12-month period of
dosing with synthetic storm water under varying hydrology and nitrogen loading
rates. All the studied bioretention systems could achieve very good ammonia
removal (more than 95%) at an average inflow ammonia concentration of (5.45+/
2.21) mg.L-1. The filter media sorption, nitrification and plants uptake were the
main removal pathways for incoming ammonia. The effluent nitrate concentrations
of the CB, MB1 and MB2 were (4.04+/-2.64)mg.L-1 (31.3%), (0.84+/-1.18) mg.L-1
(85.7%), and (0.26+/-0.48) mg.L-1 (95.6%), respectively, at the average inflow
nitrate concentration of (5.88+/-2.32) mg.L-1. The use of the native species P.
alopecuroides, a submerged zone and woodchips addition could effectively decrease
the effluent nitrate concentration, reduce the washout and achieve high nitrate
removal. Both plants uptake and denitrification were the two major pathways for
removal of inflow nitrate. Inflow magnitude, antecedent dry days and inflow
nitrate concentration were the main factors influencing the effluent nitrate
concentrations for the three bioretention systems. The results highlighted that
the bioretention design of the native species P. alopecuroides incorporated a
submerged zone with 10% woodchips addition could consistently and effectively
remove storm water nitrate under hydrological regime and nitrogen loading rates.
PMID- 29965094
TI - [Effects of NO3--N Loading on the Early-Period Efficiency of Denitrification and
Carbon Releasing in Constructed Wetland Filled with Bark].
AB - The reuse of tailwater as recycled water requires an advanced nitrogen removal
treatment, during which carbon source is added based on the tailwater quality.
This study conducted an advanced nitrogen removal model test in constructed
wetland to evaluate the effects of influent NO3--N loading on denitrification and
carbon releasing. In the constructed wetland, bark was used as filler and carbon
source for nitrogen removal. The results showed that nitrogen removal was steady
in the constructed wetland filled with bark. Denitrification velocity followed
the Monod equation, and it increased as the influent NO3--N loading increased.
The saturation constant KS was 19.10 mg.L-1. NO3--N removal rate decreased as the
influent NO3--N loading increased. During the early periods of operating the
constructed wetland filled with bark, the carbon releasing amount and velocity
increased as the influent NO3--N loading increased. Both factors were positively
linearly correlated with the influent NO3--N loading. The static carbon releasing
velocity was 0.2 mg.(g.d)-1. Compared with the hollow and loose plant carbons,
such as rotten wood, bark had a better performance and a longer cycle of carbon
releasing, which made bark a good slow-release carbon source.
PMID- 29965093
TI - [Influence of Spatial Pattern of Paddy Field on the Losses of Nitrogen and
Phosphorus in Three Gorges Reservoir Area].
AB - This paper used three plots of paddy field in Wangjiagou small catchment in
Fuling District, Chongqing Municipality as a case study. Wangjiagou, located in
Three Gorges Reservoir Area, provided a good case in terms of its closeness of
surface runoff. The samples of individual rainfall of twelve times and process of
two typical individual rainfalls on three plots of sloping paddy field were
collected from 2014 to 2015. These samples were used to analyze the influence of
spatial pattern of sloping paddy field on the concentration of nitrogen and
phosphorus in the surface runoff. The samples of daily runoff in subcatchments in
2010 and 2015 were used to analyze the influence of spatial pattern change of
subcatchments' paddy field on the concentration of nitrogen and phosphorus in the
surface runoff. The results indicated that the removal rates of TN, NO3--N and TP
of paddy field at the valley bottom were higher than those in the mid-slopes. The
removal rate of TP would be higher if plot size of paddy field at the bottom got
bigger. During individual rainfall event, the losses concentration of TN, NO3--N
and TP in the paddy fields was significantly different among three different
spatial patterns during the previous period of heavy rain event, but it became
different during the next period of moderate rain event. The two subcatchments'
spatial pattern change of paddy field had weakened the intercepting purification
ability of nitrogen and phosphorus losses of paddy field in 2015, compared with
that in 2010. TN's losses concentration increased significantly during the
periods of light and moderate rain event and base flow. TP's losses concentration
fluctuated during the event from moderate rain to heavy rain. Hence, increasing
the area of paddy field of catchment and optimizing its spatial pattern
reasonably were found as effective measures to control agricultural non-point
source pollution in the Three Gorges Reservoir Region.
PMID- 29965095
TI - [Effects of Microbial Fuel Cell Coupled Constructed Wetland with Different
Support Matrix and Cathode Areas on the Degradation of Azo Dye and Electricity
Production].
AB - In this study, microbial fuel cell coupled constructed wetland (CW-MFC) was
constructed for azo dye reactive brilliant red X-3B degradation and electricity
production. The effects of support matrix and cathode areas on the degradation of
X-3B and the electricity production of CW-MFC were investigated in this work to
improve the performance of CW-MFC. The highest decolorization efficiency was
92.70% and was obtained when the CW-MFC was constructed with support matrix S3
with particle size of 10 mm and porosity of 30%. Small particle size increased
the microbial biomass of the bottom layer of CW-MFC, which would promote the
decolorization of X-3B in the bottom layer. However, it may cause the lack of
nutrition in electrode layer and the increase in resistance of mass transfer,
which would lead to the decline of electricity production. The decolorization
efficiency and the power density of CW-MFC increased concomitantly with the
increase of cathode areas, and the CW-MFC got the highest decolorization
efficiency of 99.41% when the cathode area was 594 cm2. The electricity
production performance became stable when the cathode area continued to increase,
while the decolorization efficiency declined. This may be attributed to that more
electrons were transferred to the cathode to produce current instead of used in
degradation of X-3B.
PMID- 29965096
TI - [Effects of Anode Materials on Electricity Generation and Organic Wastewater
Treatment of 6 L Microbial Fuel Cells].
AB - Anode material is one of the most important factors on the application of
microbial fuel cells for wastewater treatment due to its key role in forming
exoelectrogenic biofilm and transferring electrons along with the high investment
cost. In this study, carbon brush (CB), carbon cloth (CC) and graphite felt (GF)
were investigated as alternative anode materials for 6 L single-chamber dual air
cathode microbial fuel cells (MFCs) in terms of starting-up rate and electricity
production with artificial wastewater and slaughter wastewater. The cost
effectiveness of anode materials was also evaluated. The results showed that
anode materials had no obvious effect on the start-up of MFC. All MFCs finished
their started-up on day 24. Using artificial wastewater[acetate 1 g.L-1 in 50
mmol.L-1 phosphate buffer (PBS)] as substrate, the maximum power densities for
the CB, CC and GF-MFCs were (56.3+/-1.8) W.m-3, (46.0+/-1.7) W.m-3, and (40.8+/
1.5) W.m-3, while with slaughter wastewater MFCs could produce (19.5+/-0.8) W.m
3, (16.9+/-0.6) W.m-3, and (11.9+/-0.5) W.m-3, respectively. COD removals of all
the MFCs were approximately 90% with both artificial wastewater and slaughter
wastewater. The CB-MFCs had a cost of (3.44+/-0.08) mW.yuan-1 with the artificial
wastewater and (0.97+/-0.05) mW.yuan-1 with slaughter wastewater, which were
18.6%, 12.8% higher than that of CC-MFCs and 38.7%, 80% higher than that of GF
MFCs, respectively. These results demonstrate that carbon brush is the most
suitable material used in large-scale MFC.
PMID- 29965097
TI - [Effects of Joint-reaction Combined by Ozonation and Coagulation on Aquatic
Organic Matters].
AB - Variations of residual ozone concentration in pure water and Al2(SO4)3 solution
were studied. The spectral characteristics, contents of organic compounds and
disinfection by products (DBPs) yields in preozonated, preozonated coagulated
(POC) and ozonated combined coagulated (OC) waters were detected by differential
absorbance(DA), three dimensional fluorescence excitation-emission matrix
spectroscopy (3D-EEM), GC and TOC. The purpose of the work was to investigate the
effects of ozonation combined with coagulation on their oxidation extents of
organic matter and the production of DBPs. Studies showed that there were
remarkable differences between the two processes, POC and OC, which proved the
existence of joint interaction of ozone and coagulant. The joint interaction
involved the following aspects. 1 Decomposition rate of ozone was improved; and
the free radical production was increased during OC compared with POC. Comparing
to ozone alone, 15.2% and 23.9% more radical capture with ozone 2mg.L-1, Al3+ 1
mg.L-1, 3 mg.L-1 were detected. 2 The difference of OC and POC was found in that
organic matter removal of OC was lower than that of POC. The pathways of OC and
POC showed difference, which resulted in differences of reaction between organic
matter and disinfectant, as well as yields of DBPs. OC removed UV254 and DOC more
efficiently than single ozonation or single coagulation; but less efficiently
than POC. DCAAFP (Dichloroacetic acid formation potential) and TCAAFP
(Trichloroacetic acid formation potential) were 47 MUg.L-1 and 20.5 MUg.L-1
respectively after treatment by POC with O3 1mg.L-1and Al3+1mg.L-1, and
chloroform formation potential (CFFP) was 97.8 MUg.L-1, which were 51%, 64.6% and
41.5% respectively lower than those in the raw water. Under the same dose
conditions, DCAAFP, TCAAFP and CFFP after OC were 48.4 MUg.L-1, 21.4 MUg.L-1 and
117.3 MUg.L-1, respectively, which were 49.6%, 63% and 29.5% lower than those in
raw water. The difference between the efficiencies of POC and OC would be
enlarged with increase of coagulant dose under the same ozone dose. Considering
its safety and efficiency, the ozone dosage, adding spot and coagulant species
must be taken into account when combined treatment of preozonation and
coagulation is used; further investigations are also needed.
PMID- 29965098
TI - [Disinfection Action of Ultraviolet Radiation and Chlorination on Escherichia
coli and Poliovirus].
AB - We chose Escherichia coli (E. coli) and poliovirus as a typical pathogenic
bacterium and virus, respectively. The effects of two typical disinfectants
(chlorine and ultraviolet) on each of them were investigated based on microbial
culture and quantitative PCR methods. The results showed that Poliovirus was
appreciably more resistant to chlorine (required disinfection dose for 1-log
microbial reduction:10.14 mg.L-1.min for E. coli; 19.2 mg.L-1.min for poliovirus)
and ultraviolet (UV) light (required UV dose for 1-log microbial reduction:1.81
mJ.cm-2 for E. coli; 6.37 mJ.cm-2 for poliovirus) than E. coli for the microbial
culture. For PCR, this study revealed that 1-log gene reduction required UV doses
and ct values of at least one to two orders of magnitude higher than that for the
microbial culture. The damage of RNA in Poliovirus was more seriously than that
of DNA in E. coli. Single-stranded RNA was more sensitive to UV irradiation than
DNA. The result evaluated with the quantitative PCR method showed opposite result
to that of the traditional culture method in which the Poliovirus was more
tolerant. The required UV doses for 1-log nucleic acid reduction were 135 mJ.cm-2
and 270.3 mJ.cm-2 for E. coli and poliovirus, respectively. Nucleic acid damage
required a higher dose of disinfectants than microbial inactivation, which was
probably attributed to the phenomenon of viable but non-culturable (VBNC) cells,
other molecular targets of inactivation and the persistence of nucleic acid after
cell death.
PMID- 29965099
TI - [Adsorption of Phosphate from Aqueous Solution on Hydrous Zirconium Oxides
Precipitated at Different pH Values].
AB - In this study, hydrous zirconium oxide (HZO) samples precipitated at different pH
values were prepared, characterized and used as adsorbents to remove phosphate
from aqueous solution. The adsorption characteristics and mechanisms of phosphate
on these HZO samples were investigated. The results showed that the presence of
Na+ slightly enhanced the adsorption of phosphate on HZO samples prepared at
precipitation pH of 4.8 and 8.0, but it greatly enhanced the adsorption of
phosphate on HZO prepared at precipitation pH of 10.6. The presence of Ca2+
slightly enhanced the adsorption of phosphate on HZO prepared at precipitation pH
of 4.8, but it significantly enhanced the adsorption of phosphate on HZO samples
prepared at precipitation pH of 8.0 and 10.6. The presence of HCO3- or SO42-
inhibited phosphate adsorption onto HZO, and the inhibitory effect of these
anions on phosphate adsorption onto HZO precipitated at pH 4.8 was much higher
than that on phosphate adsorption onto HZO samples precipitated at pH 8.0 and
10.6. The phosphate adsorption was dependent upon solution pH, and it decreased
with increasing solution pH. The Langmuir, Freundlich and Dubinin-Redushckevich
(D-R) isotherm models fitted well to the adsorption equilibrium data of phosphate
on HZO samples precipitated at pH 4.8, 8.0 and 10.6. In the presence of Na+ but
in the absence of Ca2+, there was no significant difference of the maximum
phosphate monolayer adsorption capacity derived from the Langmuir isotherm model
among HZO samples prepared at precipitation pH of 4.8, 8.0 and 10.6. In the
presence of Ca2+, the maximum phosphate monolayer adsorption capacity derived
from the Langmuir isotherm model for HZO precipitated at pH 8.0 or 10.6 was much
higher than that for HZO precipitated at pH 4.8. The mechanism for phosphate
adsorption onto HZO mainly obeyed the inner-sphere complexing mechanism. The
surface chloride and hydroxyl groups played the key role in the adsorption of
phosphate on HZO precipitated at pH 4.8 or 8.0, while only the surface hydroxyl
groups played the key role in the adsorption of phosphate on HZO precipitated at
pH 10.6. Results of this work demonstrated that the HZO precipitated at pH 8.0 or
10.6 was a more promising adsorbent for removing phosphate from wastewater than
the HZO precipitated at pH 4.8.
PMID- 29965100
TI - [Performance of Polymer-based Titanium and Zirconium Oxides Composite Adsorbent
for Simultaneous Removal of Phosphorus and Fluorine from Water].
AB - A novel composite adsorbent (Ti-Zr-D201) for simultaneous removal of phosphate
and fluoride from water was prepared by loading nanosized titanium and zirconium
oxides on the anion exchange resin named D201. Combining with the
characterization of the adsorbent, adsorption isotherm experiments, effect of
solution pH experiments, competitive tests, kinetic experiments and fixed bed
column adsorption experiments were performed to explore the adsorption
performance and mechanism. The maximum adsorption capacity of Ti-Zr-D201 for
phosphorus and fluorine was 34.9mg.g-1 and 35.1mg.g-1 respectively, when the pH
value was 5.8 and the temperature was 308K. Adsorption behavior was spontaneous,
and higher temperature was favorable for phosphorus and fluoride adsorption. The
effect of pH on the adsorption of fluoride was more significant compared with the
adsorption of phosphorus. SO42-, NO3- and Cl- were selected as the competitive
ions for competition experiments, and the results indicated that Ti-Zr-D201
exhibited favorable sorption selectivity for phosphorus and fluoride compared
with the host material D201. The fitting results of the internal diffusion model
showed that there were two different adsorption stages before the adsorption
equilibrium of Ti-Zr-D201. Column adsorption experiments showed that Ti-Zr-D201
had a stable structure, excellent dynamic adsorption performance, and could be
recycled, which showed the potential of practical application.
PMID- 29965101
TI - [Effect of Different Adding Means of Ignited Water Purification Sludge on
Phosphorus Adsorption and Forms].
AB - The adsorption of external phosphorus (P) and the distribution of dissolved
inorganic P (DIP) in the sediment interstitial water and sedimentary P forms were
researched under the ignited water purification sludge (IWPS) addition (mixing
and capping). The results showed that the adsorption ability of the IWPS
increased obviously, compared with the water purification sludge (WPS). It
indicated that the Smax increased by 43.7%, the EPC0 decreased by 69.1% and the
DPS decreased by 54.4%. The contribution of P disappearance in the overlying
water had almost no difference between the mixing and capping with IWPS, but it
was obviously higher than the control in both cases. Under the mixing condition,
the adsorption of external P by unit IWPS was 2.3 times of that under the capping
condition, if the contacting probability between the IWPS and the overlying water
was considered. Under the capping condition, the DIP in the sediment interstitial
water (1-2 cm) was 33.17 times (average) of that under the mixing condition. It
was attributed to the decrease of the dissolved oxygen penetration due to
capping. Under the mixing condition, the external P tended to form Ca-P, while
the percentages of NH4Cl-P and Fe/Al-P to Tot-P were bigger under the capping
condition. It was suggested that the improvement of the sedimentary
microenvironment by mixing with the IWPS was favorable for the adsorption of the
external P and the immobilization of the internal P.
PMID- 29965102
TI - [Law of Pollutant Erosion and Deposition in Urban Sewage Network].
AB - In order to investigate the scouring and deposition law of pollutants in urban
sewer systems, the investigation of sewer systems was carried out in Xi'an. The
results showed that the thickness of sediment in the branch pipe and the main
pipe varied obviously. At the peak of the drainage, the velocity increased
gradually, and the thickness of the pipeline sediment decreased. At the bottom of
the drainage trough, the changes of the velocity and the thickness of the
pipeline sediment were opposite, with variations of 0-24 mm and 0-12 mm,
respectively. And the probability of granular contaminants sedimentation and
scouring in sewer systems was high, while the thickness of sediment in sewage
main pipe was less than the above mentioned pipes, the variation of which was 0-7
mm. In addition, the sedimentation and scouring in the main pipeline kept
relatively balanced and the thickness of sediment remained stable. In order to
clarify the relationship between the concentration of pollutants and the flow
velocity, a pilot sewer system was established. The effects of different flow
rates, which were 0.1, 0.3, 0.6, 0.9, 1.2 m.s-1, respectively, on the contents of
carbon (organic), nitrogen and phosphorus in the pipeline were studied. The
results showed that with the increase of the flow velocity, the scour intensity
increased and the concentration of pollutants in the pipeline also increased
sharply. As shown by the monitoring results of the static light scattering
particle size analyzer, the carbon organic pollutants in the pipeline were easily
adsorbed on the larger particles, while nitrogen and phosphorus pollutants were
easily adsorbed on the particles with smaller size. Analysis on the change of the
urban sewage pipeline showed, when the flow rate was less than 0.6 m.s-1, the
sedimentation of granular pollutants in the sewage was greater than the scouring
effect. When the flow velocity was higher than 0.6 m.s-1, the water scouring
intensity increased and the scouring action was greater than the sedimentation,
meanwhile, the sediments were carried by the water and the thickness of the
sediments was reduced. The increase of the organic pollutants in the sewage was
bigger than the nitrogen and phosphorus pollutants, so that the existing sewage
carbon source was improved.
PMID- 29965103
TI - [Fate of Eleven Phthalic Acid Esters in Aerobic Sewage Treatment System].
AB - Phthalic acid esters have potential environmental risk due to their endocrine
disrupting effect. The biodegradable and removal characteristics of 11
phthalicacidesters were studied. The results showed that dimethyl phthalate(DMP),
dimethoxyethyl phthalate (BMEP), diethyl phthalate(DEP), dibutyl phthalate (DBP),
diisobutyl phthalate(DIBP), dinamyl phthalate (DNPP), di-n-hexyl
phthalate(DNHP)and bis (2-ethylhexyl) phthalate (DEHP) had ready
biodegradability, dinonyl phthalate (DNP)and dicyclohexyl phthalate (DHP)could be
biodegraded but did not pass the 10 d window-period, and only 43.5% of diphenyl
phthalate (DPP) was biodegraded on 28d. The degradation curves of 11 PAEs all
obeyed typical first-order kinetics in aerobic sludge kinetics test, with the
correlation coefficient r2>0.96, the degradation rate constant was between 0.021
1.11 h-1, and the degradation half-life was between 0.625-32.7 h. In aerobic
sludge simulation test, the removal rates of 10 PAEs were>80% at hydraulic
detention time of 12h, except that DNPP was only 55%-70%. The removal rates of
all PAEs reached 90% at hydraulic detention time of 24h. The relative high
exposure in effluent for DMP, DEP, DIBP, DBP and DEHP was found by using GC/MS,
with the residue concentrations of ND-44.0, ND-12.0, 60.4-594, 88.0-823 and 130
728 ng.L-1, respectively. The results from STP model prediction showed that the
removal in STP was mainly contributed by biodegradation, but for DPP, DNP and
DEHP, the absorption removal was also an important removal way.
PMID- 29965104
TI - [Characteristics of Denitrification Inhibiting Sulfate Reducing Process].
AB - In this study, a set of two-stage UASB reactor was used to study the
characteristics of denitrification inhibiting sulfate reduction in oil field
gathering and transportation system and some high salt wastewater, and the
characteristics of granular sludge and microbial characteristics were studied
after the stable operation of the process. The results showed that the addition
of NaNO2 increased the number of denitrifying bacteria (DNB) from 7.0*103
CFU.(100 mL)-1 to 7.3*105 CFU.(100 mL)-1 and remained stable in the process from
start to mature. The competitive inhibition caused by DNB decreased the number of
SRB from 8.0*105 CFU.(100 mL)-1 to 7.6*104 CFU.(100 mL)-1. Meanwhile, the sulfate
reduction was inhibited, and the inhibition rate increased and finally stabilized
to 82%. The study on mass ratio of microbial mass to nitrite effecting on
denitrification efficiency showed that the inhibition rate of S2- was the
highest, reaching 92%, when the mass ratio was 1200. The inhibition rate of the
process could remain at about 92%, with good stability. The particle size and
sedimentation rate of granular sludge were measured to determine whether the
process conditions were favorable for the formation of granular sludge. The study
showed that the denitrifying granular sludge formed was brown, basically
ellipsoidal and spherical, with smooth surface and high density. Before the
denitrification inhibition, the particle size of granular sludge was 1.0-1.4 mm
and the average diameter was 1.17 mm, and after denitrification inhibition, the
particle size distribution was 1.2-1.6 mm, the average particle size was 1.21 mm,
which indicated that the denitrification inhibition increased the size of
granular sludge. The average sedimentation velocity of denitrifying granular
sludge was 47.6 m.h-1, which revealed the good settling performance of the
granular sludge. The results of PCR-DGGE analysis showed that the denitrification
inhibition reduced the number of microbial species from 18 to 14 and the number
of dominant species decreased from 4 to 3, indicating the decreasing microbial
diversity. The similarity of microbial population before and after nitrification
was 62.6% and the population structure changed greatly from SRB to DNB. The
number of dominant SRB species decreased from 4 to 2 after denitrification
inhibition and the abundance of every species decreased obviously. The main
functional bacterial species of the inhibition process was uncultured
Sulfurimonas sp., which is a kind of autotrophic denitrifying bacteria. It
dominated and competed with SRB for electrons, inhibiting the sulfate reduction
and the production of sulfide.
PMID- 29965105
TI - [Enhanced Short-cut Denitrification by Fe(0)-activated Carbon and Its Influencing
Factors].
AB - In order to reduce the carbon source for biological short-cut denitrification,
Fe(0)-activated carbon was used to enhance nitrogen removal in the absence of
organic carbon, and the influences of the Fe/C mass ratio and initial pH value on
the nitrogen removal efficiency were explored. The results showed that the
nitrite removal efficiency increased from 7.4% to 31.1% when the Fe(0)-activated
carbon was used to enhance short-cut denitrification. When the Fe/C mass ratio
was reduced from 2:1 to 1:1 and 1:2, both the denitrification rate and nitrite
removal efficiency first increased and then decreased. At a Fe/C mass ratio of
1:1, a maximum denitrification rate of 5.58 mg.(g.h)-1 and a maximum nitrite
removal efficiency of 41.1% were achieved, respectively, and 0.1 mg of nitrous
oxide was emitted. When the pH value was increased from 6.0 to 9.0, the
denitrification rate decreased from 7.39 to 5.96 mg.(g.h)-1, and the nitrous
oxide emission decreased from 0.19 to 0.12 mg. Therefore, a higher nitrogen
removal efficiency could be achieved by Fe(0)-activated at a Fe/C mass ratio of
1:1 and pH value of 6.0. However, more nitrous oxide would be emitted at a low pH
value.
PMID- 29965106
TI - [Comparison of Operating Performance of Partial Nitritation Systems with Two
Different Inhibition Strategies].
AB - Two SBRs which were under high ammonia loading[1 kg.(m3.d)-1] and different dual
inhibition with feed-batch were employed to study how to control the stability of
partial nitritation system. The experimental result showed that the dual
inhibition of FNA and DO or FA and DO could implement partial nitrification
process at 35C+/-1C and the ammonia concentration of 1000 mg.L-1. The effluent
NO2--N/NH4+-N ratio was about 1, and the effluent NO3--N concentration was close
to 0, which was suitable for the appropriate influent for the ANAMMOX. In R1,
under the dual inhibition of high FA and low DO concentration, the nitrite
oxidizing rate was reduced from 28.16 mg.(g.h)-1 to 0.3 mg.(g.h)-1 (calculated as
NO2--N, the same as below). The ammonia oxidizing rate decreased by 43.60%, which
was stable at about 20 mg.(g.h)-1 (calculated as NH4+-N, the same as below). In
R2,under the dual inhibition of high FNA and low DO concentration, the nitrite
oxidizing rate reduced from 12.37 mg.(g.h)-1 to 0.02 mg.(g.h)-1. But the ammonia
oxidizing rate remained at a higher level[45 mg.(g.h)-1]. Comparing the
nitrification performance of the two SBRs under different control strategies, the
dual inhibition of high FNA and low DO concentration had the advantages of short
cultivation period, high biological activity and stable operation. It is
therefore more suitable for the achievement of the partial nitrification.
PMID- 29965107
TI - [Effect of Substrate Ratio on Nitrogen Removal Performance of ANAMMOX in ABR].
AB - In order to solve the problem of low nitrogen removal caused by incomplete
removal of anaerobic ammonium oxidation (ANAMMOX) substrate, The nitrogen removal
performance of the ANAMMOX was investigated by controlling different influent
substrate ratios in an anaerobic baffled reactor (ABR). The result showed the
optimal influent NO2--N/NH4+-N was 1.34 with which the NH4+-N and NO2--N removal
efficiencies were about 99.99% and the total nitrogen removal efficiency reached
a peak of 87%. When the influent NO2--N/NH4+-N gradually reduced from 1 to 0.49
and increased from 1.34 to 1.62, the absolute removal of NH4+-N and NO2--N was
stable in the reactor and no significant inhibition was observed in the system.
Under the condition of different substrate ratios, the removal of NH4+-N and NO2-
N was basically consumed in the first compartment of ABR, the change of substrate
ratio did not have an obvious impact on the nitrogen removal performance of each
compartment in the ABR, thus, the ABR ANAMMOX system had good stability to the
change of substrate concentration.
PMID- 29965108
TI - [Effects of Temperature on the Characteristics of Nitrogen and Phosphorus Removal
and Microbial Community in SCSC-S/Fe].
AB - In order to investigate the effect of temperature on the cellulose-degrading
bacteria and denitrifying bacteria, the denitrification and phosphorus removal of
solid carbon source of cellulose corncob+sulfur/sponge iron nitrogen and
phosphorus removal composite system, abbreviated as SCSC-S/Fe, was analyzed under
different temperature conditions, and the surface structure and microbial
properties of corncob before and after reaction were analyzed by scanning
electron microscope (SEM) and MiSeq high-throughput sequencing technologies. The
results indicated that when temperature increased from 15, 20, 25 to 30C, the
average TN removal rate of the system increased from 78.88% to 92.70%, the
average removal rate of TP increased from 82.58% to 89.15%;microbial properties
showed that the surface reaction after corncob was dominated by spherical and rod
shaped microorganisms; the proportion of cellulose-degrading bacteria was 11.01%
higher at 30C than 20C, and the proportion of denitrifying bacteria decreased by
21.26%. It can be seen that the cellulose -degrading bacteria were more sensitive
to the temperature than the denitrification bacteria, and more obviously affected
by the temperature.
PMID- 29965109
TI - [Analysis on Performance and Microbial Community Dynamics of a Strengthen
Circulation Anaerobic Reactor Treating Municipal Wastewater].
AB - A strengthen circulation anaerobic reactor (SCAR) treating artificial municipal
wastewater was investigated under different volumetric loading rate(VLR) and the
reactor performance, characteristics of granular sludge and microbial community
structure were also tested in this experiment. The results of the experiment
demonstrated that the hydraulic retention time (HRT) of 6h could be regarded as
the key parameter dominating the efficient operation of SCAR reactor, in which
condition the COD removal efficiency was above 75%. The coenzyme F420and the
maximum specific methanogenic activity (SMA) of granular sludge increased with
increasing VLR, and the EPS contents, especially TB-EPS in the granule sludge
also increased obviously. Consistently, the characteristics of anaerobic granular
sludge and the removal efficiency of the reactor were influenced by both sludge
loading and HRT. The microbial community structure and its spatial distribution
in the reactor were also affected by sludge loading, while the relative abundance
of the microbial community with different metabolic characteristics in different
spatial positions changed with the adjustment of the sludge loading.
PMID- 29965110
TI - [Aerobic Degradation Characteristics of the Quinoline-Degrading strain
Ochrobactrum sp. and Its Bioaugmentation in Coking Wastewater].
AB - Quinoline is one of the common refractory organic pollutants in coking
wastewater. An aerobic bacterial strain KDQ3 capable of utilizing quinoline as
the sole source of carbon, nitrogen and energy was isolated from activated sludge
of a coking wastewater treatment plant. The morphological properties and the 16S
rDNA sequence identified KDQ3 as Ochrobactrum sp.. The optimized temperature and
initial pH for quinoline degradation were 37C and 7.0-8.0, and the degradation
kinetics fit with Haldane's model. KDQ3 could degrade 200 mg.L-1 quinoline in the
presence of 10.4 mg.L-1 hexavalent chromium. In addition, KDQ3 was able to
degrade quinoline in real coking wastewater of aerobic tank and improve the
removal of COD, indicating that KDQ3 had the potential of bioaugmentation for
removal of quinoline from coking wastewater.
PMID- 29965111
TI - [Manganese Oxidation Characteristics and Oxidation Mechanism of a Manganese
Oxidizing Bacterium Arthrobacter sp. HW-16].
AB - Manganese is a common inorganic pollutant, which is difficult to remove from the
environment. In this research, a high efficient manganese-oxidizing bacterium
Arthrobacter sp. HW-16 was isolated from the manganese-rich soil using selective
media. Besides, high-throughput sequencing revealed that there were significant
differences of the microbial community compositions when bacteria were acclimated
in different conditions, and Arthrobacte was the dominant genus in Mn(II)
containing media. In this paper, the microbiological properties of strain HW-16
and Mn(II) oxidation mechanism were investigated. The results indicated that the
maximal Mn(II) tolerance mass concentration of strain HW-16 was 5000 mg.L-1,and
it exhibited a decent Mn(II) oxidation efficiency with the highest value of
66.28% at a Mn(II) concentration of 3000 mg.L-1. Single factor experiments
demonstrated that environmental factors could affect the growth and Mn(II)
oxidation efficiency of strain HW-16. At 30C or pH 7.0, at 1% or 3% salinity, and
at 200 r.min-1, strain HW-16 got the highest biomass. While the highest Mn(II)
oxidation efficiency occurred at high temperature (>=40C), high pH (>=7), high
shaking speed and low salinity. Strain HW-16 could oxidize Mn(II) by producing
Mn(II) oxidizing active factor and turn Mn(II) into precipitation by synthesizing
alkaline metabolites.
PMID- 29965112
TI - [Effect of Temperature on Nitrogen Removal Performance of Marine Anaerobic
Ammonium Oxidizing Bacteria].
AB - The effect of temperature on the nitrogen removal performance of marine anaerobic
ammonium oxidizing bacteria processing sewage seawater was studied by employing
an ASBR reactor, and the dynamic characteristics of the marine anaerobic ammonium
oxidizing bacteria at different temperatures were simulated by modified Logistic
model. The experimental results indicated that the nitrogen removal performance
was affected little at 25-35C. The total nitrogen removal efficiency (TNRE)
remained at (82+/-2)% and the total nitrogen removal rate (TNRR) was stabilized
at (0.62+/-0.01) kg.(m3.d)-1. When the temperature was 20C, TNRE increased from
59% at the beginning to 79% after 13 days. This indicated that the marine anammox
bacteria still had strong ability of nitrogen removal, and the reactor in the low
temperature treatment of sewage containing seawater had a good potential.
However, when the temperature dropped to 10-15C, the nitrogen removal performance
of the reactor was inhibited. TNRE decreased to (40+/-8)% and (11+/-4)%,
respectively. Besides, TNRR also decreased to (0.30+/-0.04) kg.(m3.d)-1 and
(0.08+/-0.03) kg.(m3.d)-1, respectively. According to the Arrhenius equation, the
activation energy for marine anaerobic ammonium oxidation reaction was 26 kJ.mol
1 at 25-35C, and the activation energy of marine anaerobic ammonium oxidation
reaction was 76 kJ.mol-1 at 10-25C. In addition, dynamic analysis was performed
by Logistic model and the NRE and effluent total nitrogen concentration (ceff) at
different temperatures were forecasted. The correlation coefficient R2 was
between 0.9668 and 0.9957.
PMID- 29965113
TI - [Nitrogen Removal Performance and Microbial Community Analysis of Activated
Sludge Immobilization].
AB - Immobilization of activated sludge was used to further remove nitrogen from
secondary effluent. Intermittent sequencing batch reactor experiments were
conducted to measure nitrogen removal in synthetic wastewater with initial total
nitrogen concentrations (TN) of 10-45 mg.L-1 and C/N ratio of 1.78-10, and
microbial community characteristic of embedding beads was investigated. When the
packing ratio of embedding beads was 10%, and the temperature of wastewater,
dissolved oxygen (DO), initial concentration of chemical oxygen demand (COD) were
maintained at 10-15C, 2-4 mg.L-1, and 80-100 mg.L-1, respectively, the results
showed that the maximum total nitrogen removal loads ranged from 7.78 to 23.18
mg.(L.h)-1during the stable phase. SEM observations showed that the embedding
beads were highly porous and microorganisms adhered to the interior and external
surface of embedding beads, demonstrating that embedding beads acted as an ideal
support material. Based on high-throughput sequencing analysis, the structure of
microbial communities in the beads'interior and exterior changed significantly
compared with embedding activated sludge. The advantage of denitrifying bacteria
in embedding beads was obvious and the microbial diversity was good. Some
microorganisms which can conduct both heterotrophic nitrification and aerobic
denitrification, were identified. These processes may facilitate pathways for
untraditional biological denitrification in the beads'interior.
PMID- 29965114
TI - [Microbial Structure of an Enhanced Two-phase High-solid Anaerobic Digestion
System Treating Sludge].
AB - High-solid anaerobic digestion (HSAD) of sludge has several advantages like
smaller reactor, lower energy consumption and less digestate. However, the
understanding about the mechanism especially the microbial mechanism is still
limited. In this study, microbial communities of a pilot-scale sludge HSAD system
at steady state were investigated with 16S rRNA clone library technology. The
system employed an enhanced two-phase anaerobic digestion process, i. e.
'hyperthermophilic acidogenesis (70C, 3 d)-thermophilic methanogenesis (55C, 12.5
d)' to treat waste activated sludge with a solid content of about 9%. The
volatile solid (VS) removal rate was 35.7% and methane yield (CH4/VSremoved) was
0.648 m3.kg-1. The bacterial compositions of the two phases were significantly
different:there were plenty of proteolytic bacteria in hyperthermophilic
acidogenesis phase; and the bacteria degrading polysaccharides like cellulose and
the bacteria utilizing long-chain fatty acids were found in thermophilic
methanogenesis phase; some bacteria degrading simple saccharides existed in both
phases. In both phases, the dominant archaea were Methanothermobacter.
Especially, 100% of the retrieved archaea in the thermophilic methanogenesis
phase belonged to genus Methanothermobacter. This indicated that hydrogenotrophic
methanogenesis was the predominant methanogenesis pathway in this system since
methane was only detected in the methanogenesis phase.
PMID- 29965115
TI - [Comparative Studies on Soil Actinobacterial Biodiversity After Re-vegetation in
the Urban and Rural Hydro-fluctuation Zone of the Three Gorges Reservoir Region].
AB - This study aimed to understand the soil actinobacterial community diversity in
the urban and rural hydro-fluctuation zone of the Three Gorges Reservoir region.
The hydro-fluctuation zone of Chongqing Great Theatre in Jiangbei District and
the Ruxi river basin in Zhong County, Chongqing, was chosen as the study area.
Soil samples were collected in June 2015, to measure actinobacterial biodiversity
using the terminal-restriction fragment length polymorphism (T-RFLP) molecular
method. Results showed that:1 The actinobacterial biodiversity was different in
the urban and rural hydro-fluctuation zone after artificial vegetation
restoration. The actinobacterial biodiversity of the urban hydro-fluctuation zone
was significantly higher than that of the rural hydro-fluctuation zone (P<0.05),
which was most obvious in the surface soil. 2 The actinobacterial biodiversity of
woodland was higher than that of grassland, but there was no significant
difference in the actinobacterial biodiversity among the three soil layers in
both the urban and rural hydro-fluctuation zone. 3 The dominant species of
actinomycetes was different in different samples. 4 Redundancy analysis and the
Monte-Carlo test revealed that water content and available nitrogen (AN) played a
critical role in influencing actinobacterial biodiversity in the urban hydro
fluctuation zone (P<0.05). In contrast, the water content, organic matter (OM),
available nitrogen (AN) and available phosphorus (AP) played a critical role in
influencing actinobacterial biodiversity in the rural hydro-fluctuation zone of
the Three Gorges Reservoir region (P<0.05). Thus, we concluded that the
actinobacterial biodiversity of the urban hydro-fluctuation zone was
significantly higher than that of the rural hydro-fluctuation zone in the Three
Gorges Reservoir region, and such a result was attributed to the increased human
disturbance and soil nutrients.
PMID- 29965116
TI - [Nitrous Oxide Emissions and Its Influencing Factors from an Agricultural
Headwater Ditch During a Maize Season in the Hilly Area of Central Sichuan
Basin].
AB - Agricultural headwater ditches, the important locations for retaining and
transforming nitrogen derived from the adjacent farmlands, have been regarded as
the potential source of nitrous oxide (N2O) emission. In this study, N2O
emissions from a typical agricultural ditch in the Hilly Area of Central Sichuan
Basin, were observed by closed static chamber-GC technique during the maize
season (rainy season), from June to the end of September. During the study
period, cumulative N2O emissions in the sediment-water interface without
vegetation (NV) and the ditch ecosystem with natural vegetation (V) were 0.07 and
0.43 kg.hm-2, respectively. Meanwhile, the mean N2O flux from the agricultural
headwater ditch ecosystem[14.7 MUg.(m2.h)-1] was comparable to the magnitude of
direct N2O flux from the maize cropland in this region. Nitrate concentration in
the overlying water could be the main factor governing N2O emission from the
ditch, especially in the rainy season. The existence of vegetation increased the
indirect N2O emission factor (V:0.05% vs.NV:0.01%). The indirect N2O emission
factor from this field investigation was much lower than the default value
proposed by the Intergovernmental Panel on Climate Change (IPCC, 2006) for
assessing indirect agricultural N2O emissions. More attention should be paid to
in situ measurements to reduce uncertainty of N2O estimation calculated by only
applying the default value for emission factor from the IPCC.
PMID- 29965117
TI - [Effect of Dicyandiamide on N2O Emission in Fallow Paddy Field and Rape
Cropping].
AB - The emissions of greenhouse gas in winter are often neglected, and the latest
research results showed that N2O emissions in fallow paddy field and winter
oilseed rape are still large, research on mitigating the N2O flux and the
mechanism behind them is of significance for mitigating N2O emissions from
agricultural soil. By using static chamber techniques and molecular biology
techniques, the N2O emission as well as the community composition and abundance
of ammonia oxidizing archaea (AOA) and ammonia oxidizing bacteria (AOB) from
fallow paddy field, rape cropping with and without DCD treatment in Taoyuan
agricultural ecological experiment station of the Chinese Academy of sciences
were measured. The results showed that the addition of DCD significantly
inhibited N2O emissions in fallow paddy field and rape cropping by 36.7% and
23.6%, respectively. The application of DCD in fallow paddy field inhibited the
abundance of AOA and AOB by 59.3% and 73.7%, respectively, but only changed the
community structure of AOA. The addition of DCD in rape cropping only changed the
community structure and inhibited the abundance of AOB. This research showed that
DCD application could effectively mitigate the N2O emissions in fallow paddy
field and winter rape cropping under different mitigation mechanisms.
PMID- 29965118
TI - [Characteristics of Biochar-mediated N2O Emissions from Soils of Different
Surface Conditions].
AB - It was aimed to investigate the response to biochar addition on N2O gas
production and emission in different surface conditions. To study the dynamic
changes of soil N2O release, soil nitrate(NO3--N) and ammonium(NH4+-N), a field
trials experiment was conducted from 2014 to 2015 in wheat and corn season, which
contained three treatments[the blank control group (CK), biochar applied at 5
t.(hm2.a)-1(BC5) and 45 t.(hm2.a)-1(BC45), respectively] under crop
cultivation(+) and non-cultivation(-) condition. The results indicated that:1
During the season of wheat growth, the soil N2O emissions of CK+, BC5+, BC45+
were 21.70-88.91, 21.42-130.09, 64.44-179.58 MUg.(m2.h)-1 respectively, and that
of BC45+ possessed a higher value than those of the other treatments(P<0.05).
Compared with wheat winter period, the soil N2O emissions of the three treatments
decreased evidently in wheat peak stage(returning green and jointing stage,
booting and heading stage) (P<0.05), and the amplification of BC45+ reduced by
18.43% and 14.62% in comparison with CK+ and BC5+ in wheat booting and heading
stages. In the early stage of maize growth, the soil N2O emissions of BC45+ were
significantly increased compared with CK+ and BC5+(P<0.05). However, there were
no significant differences among treatments of maize heading stage and mature
stage. It showed that the biochar-mediated promotion effect of soil N2O emissions
was effectively inhibited by crop growth and the increase of surface mulch.
Besides, the result of soil N2O release in the same treatment had also confirmed
this conclusion in bare land. 2 Under the conditions of wheat cultivation and
homochronous non-cultivation, the soil NO3--N and NH4+-N contents of BC5+ and
BC45+ treatments were raised with respect to CK+, but the values dropped
significantly in wheat peak stage, especially for BC45+ treatment, with 96.44%
and 69.40% decrease respectively. The soil inorganic nitrogen content of maize
growth season had a similar trend in wheat season. Parallel to this result of the
apparently falling soil NO3--N and NH4+-N concentrations, the soil N2O emissions
of BC45+ also declined remarkably in peak stage. The decline in respiratory
substrate caused by the increase of nitrogen uptake by crop growth, may be one of
the reasons for the decrease of N2O emission. 3 In wheat growth season, the soil
pH values of the biochar treatments were improved from 4.62 to 5.18. In maize
season, the soil pH values ranged from 4.42 to 5.02. When the soil pH value was
relatively low, the soil N2O emission was high, and vice versa. The soil N2O
emission was partly influenced by the soil pH value.
PMID- 29965119
TI - [Characteristics of Soil Respiration and Soil Organic Carbon in Fava Bean
Farmland Under Ridge Tillage and Straw Mulching in Southwest China].
AB - Soil respiration is an important process for carbon emission. A field study was
conducted with four treatments including T (traditional tillage+straw mulching
level 0 kg.hm-2), R (ridge tillage+straw mulching level 0 kg.hm-2), RS1 (ridge
tillage+straw mulching level 3750 kg.hm-2), and RS2 (ridge tillage+straw mulching
level 7500 kg.hm-2), so as to probe the effects of ridge tillage and straw
mulching amount on soil respiration and soil organic carbon(SOC) and the
relationships of soil respiration rate with soil temperature and water content
(SWC) during the growth period of fava bean in the triple intercropping system of
fava bean/maize/sweat pomato in dryland region of southwest China known as the
purple hilly region. The changes of soil respiration rate were in accordance with
crop growing, being firstly increased and then decreased during the whole growth
period of fava bean, and there were significant differences in soil respiration
rate among different treatments, which could be ranked as RS2[3.365 g.(m2.d)-1] >
RS1[2.935 g.(m2.d)-1] > T[2.683 g.(m2.d)-1] > R[2.263 g.(m2.d)-1]. Ridge tillage
reduced soil respiration in fava bean farmland, whereas straw mulching treatment
increased it, whose variation trend was in accordance with that of straw mulching
levels. There was a significant exponential relationship between soil respiration
and soil temperature at 5 cm and 10 cm depth, and the exponential model at 10 cm
produced better fitness than that at 5 cm. The temperature sensitivity (Q10) at
10 cm could be ranked as RS2 > RS1 > R > T, being 1.751,1.665,1.616, and 1.35,
respectively. The combined exponential model indicated that soil temperature and
water content (SWC) could jointly explain 68%(R), 79%(RS1) and 76%(RS2) of
variation in soil respiration. This study results suggested that ridge tillage
and straw mulching significantly increased SOC of 0-5 cm, 5-10 cm, 10-20 cm and
20-30 cm soil layers, and the increase of SOC was in accordance with that of
straw mulching levels. The SOC was significantly increased in 5-10 cm and 10-20
cm soil layers, which could be ranked as RS2 > RS1 > R > T, and the increases in
SOC at 5-10 cm were especially notable. The weighted average of particulate
organic carbon (POC) at 0-30 cm was significantly increased, but the proportion
of POC in SOC did not show significant influence.
PMID- 29965120
TI - [Prediction of Distribution of Soil Cd Concentrations in Guangdong Province,
China].
AB - Heavy metals are one of the principal soil pollution sources. Contaminated soils
affect the quality of agricultural products, and then threaten human health.
Prediction of the contaminants distribution in the soil is the foundation of
pollution evaluation and risk control. A total of 1000 soil profiles were
collected to investigate the spatial variation of soil cadmium (Cd) concentration
in Guangdong province. These datasets were divided into two groups, about 900
samples for model training and the other 100 for model validation. Six frequently
used GIS spatial interpolation methods including Spline, Natural Neighbor,
Ordinary Kriging, Inverse Distance Weighted, Local Polynomial Interpolation and
Radial Basis Function, and Cubist which is a type of rule-based model were
compared to determine their suitability parameters for estimating soil Cd
concentration. Nine different resolutions including 2000, 1500, 1000, 800, 500,
300, 200, 150, and 90 m were selected to calculate, evaluate and compare their
accuracy. The results showed that, 1 Quantitative assessment of the continuous
surfaces showed that there was a large difference in the accuracy of the seven
methods. Cubist was superior to GIS-based spatial interpolation methods at all
resolutions. Cubist was the best tool for mapping the spatial distribution of Cd
in soils with thirty-seven specific predictors relevant to the source and
behavior of Cd (parent material, land use, soil type, soil properties, population
density, gross domestic product per capita, and the lengths and classes of the
roads surrounding the sampling sites, climatic factors, etc.) at 300 m*300 m
resolution. The second was Spline, its accuracy was optimal at the 1500 m*1500 m
resolution. 2 Results of Cubist suggested that the soil Cd spatial distribution
was primarily dependent on the properties of soil regional parent materials. And
soil samples with higher Cd concentration mainly located in Carboniferous and
Quaternary areas. 3 Spatially, Cd concentrations were higher in the Pearl River
Delta region and north of Guangdong Province. Many hotspots existed throughout
the Pearl River Delta region due to transportation and pollution of the river.
The major anthropogenic inputs of heavy metals to soils and the environment were
metalliferous mining and smelting in the north of Guangdong Province. The soil Cd
geometric mean concentration of 0.147 mg.kg-1 was lower than that of China,
however it varied from zero to 6.056 mg.kg-1. The areas with soil Cd
concentrations greater than 1.0 and 3.0 mg.kg-1 were 160 km2 and 2140 km2
respectively, accounting for 0.09% and 1.18% of the total area of Guangdong
Province.
PMID- 29965121
TI - [Spatial Distribution and Potential Ecological Risk Assessment of Heavy Metals in
Sediments of Suya Lake].
AB - In order to study the pollution status of heavy metals in sediments of Suya Lake,
the concentrations of heavy metals Cu, Cd, Cr, Zn, Pb and Ni in sediments were
measured at three locations in the center, middle and periphery of Suya Lake, the
content characteristics and the pollution status of heavy metals in the study
area were analyzed by the method of geoaccumulation index and potential
ecological risk index, and the distribution and interrelation of heavy metals
were evaluated by Kriging method and correlation analysis. The results showed
that, on average, Zn was the highest, 112.87 mg.kg-1, followed by Cr, the
smallest average of Cd was only 0.41 mg.kg-1. In addition to Cd and Cr, the
coefficients of variation of Cu, Zn, Pb and Ni were relatively small, ranging
from 24% to 31%, with moderate degree of variation. The coefficients of variation
of Cd and Cr were 50.41% and 41.92%, respectively, and the spatial variation was
obvious, which indicated that the variation of Cd and Cr was more significant
than the others; 2The heavy metals Cu, Cd, Cr, Zn, Pb and Ni had a strong linear
relationship, and there was a significant positive correlation, and six kinds of
heavy metals had some homologous characteristics, with a common external input;
3The main pollution elements in the study area were Cd, Cr and Zn, the pollution
degree was relatively serious, and the scope was extensive. Among them, the
pollution degree of Cd was the most serious, the overall pollution level was
moderate, and the pollution degree in some sample areas reached up to severe
pollution, the pollution status of Cr, Zn and Pb was relatively mild, the
pollution status of Cu, Pb and Ni was better, and there was no ecological risk;
4On the whole, the pollution level of the northeastern part of Suya Lake was
relatively light, the degree of pollution in the southwest was relatively
serious, showing a significant spatial distribution characteristics of decreasing
from southwest to northeast, the contents of heavy metals in the samples were
higher than those in the southwest of the reservoir, while the northeastern part
of the periphery was the area with accumulation of low concentrations of heavy
metals., and there was no pollution from Cu, Cr, Zn and Ni.
PMID- 29965122
TI - [Effects of the Active Components of Humic Acids and Their Proportions on the
Dynamics of Lead Transformation and Availability in Purple Alluvial Soil].
AB - Humic acids (HAs) play important roles in mediating the occurring forms and
activity of Lead (Pb) in soils. Simulating experiments together with chemical
sequential extraction were carried out to understand the dynamics of lead
transformation and availability in purple alluvial soil as influenced by humic
acid (HA) and fulvic acid (FA) and their ratios (HA/FA). The main results
obtained are as following:1 The distributions of Pb forms bound by Fe-Mn oxides
and organic matter increased, while the proportions of exchangeable Pb and
residual Pb fraction decreased after the establishment of transformation
equilibrium in 60 d. 2The exchangeable-Pb and carbonate bound Pb showed highest
positive contribution to the availability of Pb in the tested soil; and HA
passivated soil Pb activity by decreasing the proportion of carbonate bound Pb
and FA activated soil Pb by increasing the proportions of exchangeable Pb and
carbonate bound Pb. The passivation or activation roles increased with increasing
amount of HA or FA; A sharp increase of soil Pb availability occurred at FA
dosage higher than 1% as C basis, suggesting that 1% (C) exogenous FA was the
change-point for soil Pb activation;3The overall effects of HAs depended on its
ratio of HA/FA at a constant addition of HAs (1% C). HAs suppressed soil Pb
activity at a ratio of HA/FA >=7/3, while they activated soil Pb activity at a
ratio of HA/FA<=5/5. The transformation extent and direction of Pb in soils
differed at various dosage and ratios of HA/FA, resulting in different overall
effects on the Pb availability in soil.
PMID- 29965123
TI - [Enrichment Characteristics of Heavy Metals in Particulate Organic Matter of
Purple Paddy Soil].
AB - Twenty purple paddy soil samples were collected from the Prefectures of Hechuan
and Tongliang, Chongqing, and sieved into particulate organic matter (0.053-2 mm,
POM), sand fraction (0.053-2 mm) and fine soil fraction (<0.053 mm). By comparing
the concentration and distribution of soil organic carbon (SOC) and heavy metals
among different components, the enrichment characteristics of POM for heavy
metals (Cu, Zn, Pb and Zn) and its relationship with soil properties such as pH,
CEC, clay content (<0.002 mm) and SOC were investigated. The result showed that
the contents of POM fraction in purple paddy soils ranged from 7.31 to 44.76 g.kg
1, with an average level of 19.20 g.kg-1, while the carbon contents ranged from
96.61 to 263.17 g.kg-1, which were significantly higher than those of their
original soils and other two fractions. The contribution rates of organic carbon
by POM to the total organic carbon of soils ranged from 8.63% to 48.62%, which
accounted for a large pool of organic carbon. The average enrichment factors of
POM fraction to Cu, Zn, Pb and Cd were 3.35, 1.14, 2.88 and 2.14, respectively.
Compared with sand fraction and fine soil fraction, POM fraction showed a
significantly higher contribution rate to heavy metals, which were 6.02%, 2.22%,
5.24% and 3.21%. In addition, the enrichment ability and contribution rate of POM
to Cu and Pb were obviously greater than those of Zn and Cd. There was a
significant positive correlation between content of POM fraction and soil
properties such as SOC, pH, CEC and clay content, in which SOC was the key
factor. The POM-C content and total amount were significantly correlated with SOC
and clay content. The pH value, SOC and POM-C amount had a significant or
extremely significant correlation with the amount of heavy metals in POM, in
which SOC was the most critical one. Comparing with other heavy metals, the
amount of zinc in POM had the highest regression coefficient and the closest
relationship with soil properties.
PMID- 29965124
TI - [Enhanced Sorption of Cetirizine to Loessial Soil Amended with Biochar].
AB - Biochar could be used as a stabilizer to control the migration and transformation
of pollutants in soil and reduce their environmental risks. Cetirizine (CTZ) was
selected as a target pollutant to investigate the effect of biochar on sorption
characteristics of loessial soil by batch experiments. Biochars were produced
from walnut shell at different temperatures and added to soil at different mass
ratios. The results indicated that all biochars showed obviously higher sorption
capacity than loessial soil. The sorption capacity for CTZ was obviously enhanced
by soils amended with biochars produced at 400-700C, which could be attributed to
the increased bulk carbon content and specific surface area (SA). Sorption of CTZ
to mixtures, excluding the soils amended with biochar produced at 300C, was lower
than the theoretical value. This could be due to the cross-effect between soil
components and biochar. At the same time, the organic matter and native sorbates
in soil may block or compete for adsorption sites on biochar surface. Biochars
would be helpful to stabilize the loessial soil contaminated with CTZ. However,
for relatively low concentration of CTZ in aqueous solution and soils amended
with relatively high biochar mass ratio, the sorption capacity of the mixtures
could be overestimated theoretically without considering the cross-effect between
soil and biochar.
PMID- 29965125
TI - [Characteristics and Mechanism of Copper Adsorption from Aqueous Solutions on
Biochar Produced from Sawdust and Apple Branch].
AB - In order to utilize the waste biomass resources efficiently, two raw materials of
sawdust and apple branch were selected to produce biochars at 450C by oxygen
limited pyrolysis, and the adsorptions of Cu2+ in aqueous solutions were
evaluated. The effects of initial Cu2+ concentration and contact time in batch
sorption experiments were investigated by the four kinds of isothermal adsorption
models (Langmuir, Freundlich, Temkim, D-R model) and the four kinds of adsorption
kinetics models (Pseudo first-order, Pseudo second-order, Elovich model,
Intraparticle diffusion model). The influencing factors of adsorption
characteristics about sawdust biochar (JB) and apple branch biochar (PB) were
discussed by characterizing their elemental composition, functional groups,
surface area, surface morphology and scanning electron microscope. The results
showed that:1The adsorption equilibrium of PB and JB was reached in three hours
and six hours, respectively, and the maximum adsorption capacity of PB and JB
reached 15.85 mg.g-1 and 17.44 mg.g-1, respectively. Compared with other studies,
these biochars showed higher Cu2+ adsorption performance. 2The adsorption
kinetics was best fitted by the pseudo-second order model, while the isothermal
adsorption was best described by Langmuir isotherms. This indicated that the
beneficial adsorption process via monolayer was affected by intraparticle
diffusion, surface adsorption and liquid film diffusion. 3The adsorption
mechanism for Cu2+ is a complex interaction of physical and chemical factors.
Electrostatic interaction of physical adsorption is mainly adsorption mechanism,
Chemical adsorption mechanism includes generally ligand exchange (phenolic
hydroxyl)/ion exchange (H+) and cationic-pi. It was demonstrated that JB and PB
could be considered as promising materials to immobilize heavy metals in
contaminated water or soil.
PMID- 29965126
TI - [Adsorption of Pb2+ and Cd2+ from Aqueous Solution Using Vermicompost Derived
from Cow Manure and Its Biochar].
AB - Using vermicompost (CV) as raw material, its biochar (CVC350) was prepared at
350C and then their physio-biochemical properties were characterized.
Furthermore, adsorption studies were performed in a batch system for removing
Pb2+ and Cd2+ ions from solution. The characterization results revealed much
higher surface area, smaller pore size, greater aromaticity and nonpolarity of
CVC350 as compared to CV. Batch adsorption experiments revealed that both the
adsorption of Pb2+ and Cd2+ onto CV or CVC350 fitted Langmuir isotherm model very
well, and the maximum adsorption capacity of Pb2+ was in the order of CVC350>CV,
but no difference was observed for the adsorption capacity of Cd2+ between CV and
CVC350. The desorption studies showed that both CV and CVC350 had much higher
adsorption rate for Pb2+ than that for Cd2+, and the Cd2+ adsorbed could be more
easily desorbed from CV and CVC350 compared with that for the Pb2+ adsorbed. Both
the dynamic adsorption process of Pb2+ onto CV and CVC350 was a rapid process,
however, the adsorption process of Cd2+ onto CV and CVC350 could be separated
into the first rapid step and the second slower step. The adsorption capacity of
Pb2+ or Cd2+ onto CV and CVC350 was only affected by the much lower initial pH of
the solution, besides, the adsorption capacity of Cd2+ onto CV and CVC350 was
relatively more influenced by the initial pH compared with that of Pb2+.
Moreover, FTIR analysis showed that the adsorption of Pb2+ and Cd2+on CV depended
on the active sites such as aliphatic alcohol, aliphatic acid,carbonates as well
as phosphate while that on CVC350 mainly relied on aromatic alcohol, aromatic
acid and carbonates.
PMID- 29965127
TI - [Performance and Mechanism Study of Visible Light-driven C3N4/BiOBr Composite
Photocatalyst].
AB - Efficient visible light-driven C3N4/BiOBr composite photocatalysts were prepared
via a facile hydrothermal method and characterized by X-ray diffraction, Fourier
transform infrared, scanning electron microscopy, UV-Vis diffuse reflectance
spectra and photoluminescence spectra for the phase composition and optical
property. Taking rhodamine B (RhB) as the target pollutant, the photocatalytic
activity and stability of photocatalysts were studied under visible light
irradiation. Furthermore, the mechanism in the process of photocatalytic
degradation was discussed by electron spin resonance spectroscopy analysis and
the trapping experiment of generated radicals. The results indicated that
C3N4/BiOBr composite photocatalysts had excellent crystallization performance.
Composited by C3N4, BiOBr exhibited considerably higher photocatalytic activity
by reducing the rate of electron-hole recombination. Among prepared composites
with various C3N4 contents, 15% C3N4/BiOBr exhibited the best efficiency for the
degradation of RhB. After irradiation for 18 minutes, the degradation rate of RhB
was 100%, which was 1.5 times higher than that using pure BiOBr. The results also
suggested that holes and .O2- were the main reactive species in the
photocatalytic process for the RhB degradation, and holes played the leading
role.
PMID- 29965128
TI - [Dry and Bulk Nitrogen Deposition in Suburbs of Xining City].
AB - This study conducted a full two-year (2014 and 2015) measurements of dry and bulk
deposition of atmospheric inorganic nitrogen (N) at the suburb of Xining city,
Qinghai province. Dry N deposition fluxes were calculated by multiplying the
atmospheric concentrations of NH3 and NO2 measured using passive samplers with
the modeled dry deposition velocities provided by the GEOS-Chem global chemical
transport model, while bulk N deposition fluxes were measured using precipitation
gauge. Annual mean concentrations of gaseous NH3 and NO2 averaged 8.8 and 19.6
MUg.m-3, respectively, with significantly higher values in 2015 than in 2014.
Seasonal mean NH3 concentrations were higher in spring and summer than in autumn
and winter, but the concentrations of NO2 changed little from season to season,
with a small peak in autumn. Annual mean concentrations of NH4+-N and NO3--N in
precipitation averaged 2.2 and 1.8 mg.L-1, respectively. Concentrations of NH4+-N
in autumn were~55% lower than those in other seasons, whereas those of NO3--N in
autumn or winter were~26% higher than those in spring and summer. Dry deposition
of NH3 and NO2 was 9.0 and 2.8 kg.(hm2.a)-1, respectively. Bulk deposition of
NH4+-N and NO3--N in precipitation was 7.6 and 6.2 kg.(hm2.a)-1, respectively.
Reduced N (gaseous NH3 and NH4+-N in precipitation) was the dominant form of N
deposition. The total dry and wet N deposition was 25.6 kg.(hm2.a)-1, which
represented significant nutrient input from the environment to the suburban
farmland, but this amount of deposited N exceeded the critical loads[10-20
kg.(hm2.a)-1] of terrestrial ecosystems, suggesting a risk of "N saturation" in
the local natural environment.
PMID- 29965129
TI - [Day-Night Variation and Source Apportionment of Carbonaceous Aerosols in PM10
During Spring and Summer of Lanzhou].
AB - The purpose of this study was to investigate the characteristics and source
apportionment of carbonaceous aerosols in PM10 for the daytime and nighttime
during spring and summer over Lanzhou. The samples were collected from 1 April
2015 to 30 August 2015, daytime samples were collected during 08:00 to 20:00 and
nighttime samples during 20:00 to 08:00 on the next day, and organic carbon (OC)
and elemental carbon (EC) concentrations were measured. The results showed that
PM10, OC and EC concentrations were (136.0+/-84.3), (12.4+/-3.2), (2.3+/-0.7)
MUg.m-3 during the daytime, and (196.0+/-109.2), (16.0+/-5.3), (5.0+/-2.1) MUg.m
3 during the nighttime. The mass concentrations of PM10, OC and EC in the
nighttime were higher than those during the daytime. The ratios of secondary
organic carbon to total organic carbon were higher in the daytime than nighttime,
suggesting that the secondary organic carbon pollution was more serious in the
daytime. In sand-dust weather, the concentrations of PM10 and OC were higher than
those in non-dust weather, while the EC concentration was close to that in non
dust weather. Secondary organic carbon and total carbon aerosols were higher in
sand-dust weather, but the contribution to the PM10 was relatively low. In
addition, principal component analysis on the eight carbon fractions of non-dust
weather indicated that coal combustion, vehicle exhaust and biomass burning were
the major sources for carbonaceous aerosol during the daytime, while coal
combustion, dust, diesel exhaust and biomass burning played important roles in
the nighttime.
PMID- 29965130
TI - [Characteristics of the Size Distribution of Water Soluble Inorganic Ions in
Sanya, Hainan].
AB - Size-resolved filter samples were collected in Sanya every other week from June
2012 to May 2014. The mass concentrations of water-soluble inorganic ions,
including anions (Cl-, NO3-, SO42-) and cations (Na+, NH4+, K+, Mg2+, Ca2+) were
measured by ion chromatography. The results showed that the total concentrations
of measured water-soluble inorganic ions were (8.91+/-7.27) and (11.34+/-9.37)
MUg.m-3 in PM2.1 and PM2.1-9, respectively. In PM2.1, SO42- and NH4+ comprised
72.2% of all water-soluble inorganic ions, while in PM2.1~9, Cl-, Ca2+ and Na+
comprised 67.6% of all water-soluble inorganic ions. In PM2.1, the total
concentrations of water-soluble inorganic ions had highest concentrations in
winter and lowest concentrations in summer. In PM2.1~9, the total concentrations
of water-soluble inorganic ions presented the highest concentrations in summer.
SO42- and NH4+ showed bimodal size distributions and the peaks in the fine mode
shifted from 0.43-0.65 MUm in spring, summer and autumn to 0.65-1.1 MUm in
winter. NO3-, Na+, Cl-, Ca2+ and Mg2+ were unimodal with the peaks in the coarse
mode of 4.7-9.0 MUm. K+ showed bimodal size distribution with the fine mode at
0.43-0.65 MUm and the coarse mode at 4.7-5.8 MUm. PCA analysis showed that water
soluble inorganic ions were mainly affected by the secondary formation, sea salt
and soil particles or falling dust.
PMID- 29965131
TI - [Pollution Characteristics of NH4+,NO3-,SO42- in PM2.5and Their Precursor Gases
During 2015 in an Urban Area of Beijing].
AB - Simultaneous measurements of precursor gases NH3,NO,NO2,SO2 and the main water
soluble ions in PM2.5 such as sulphate (SO42-),nitrate (NO3-) and ammonium (NH4+)
(collectively called SNA)were carried out in the urban area of Beijing during
2015-01 to 2015-12,which obtained 325 groups of samples. PTFE membrane filters
were used to collect particulate NH4+, NO3- and SO42-, followed by the online
instruments to collect precursor gases. The pollution characteristics of the
precursor gases and SNA were analyzed and their correlation was studied. The mean
concentrations of NH3, NO, NO2, SO2, NH4+,NO3- and SO42- were 21.5, 17.7, 54.3,
14.2, 8.1, 13.5 and 12.7 MUg.m-3 respectively during the period of monitoring,
and SNA accounted for 43.4% of PM2.5. The concentrations of SO2,NOx and SNA
declined compared to 2014. The concentrations of NO,NO2 and SO2 were highest in
winter and lowest in summer. The concentration of NH3 was higher in summer and
lower in autumn; The concentration and the percentage of NH4+ were stable during
the four seasons,both the concentrations and the percentage of NO3- were lowest
in summer. The concentrations of SO42- was highest in winter and the percentage
was lowest in summer. The ratio of ([NO3-]+2[SO42-]) and NH4+ was 0.97 during the
whole year, showing that anions mainly existed in the form of NO3- and SO42-. In
summer, the ratio of[NO3-]+2[SO42-] and[NH4+] was slightly higher than 1.0, which
was the reason why NO3- was bound to Ca2+, Mg2+ and Na+besides NH4+. With the
increase of pollution, the mass concentration of precursor gases and SNA
increased dramatically, among which NOx increased most rapidly, and SO2 decreased
from severe pollution to serious pollution. The contribution rate of NH4+ was
maintained at a relatively stable level. SO42- had a higher contribution when the
pollution level was lower, whereas the concentration of NO3- was higher than
others and contributed most to PM2.5 in heavy pollution. Heterogeneous
transformation on the surface of particulate matter played a more important role
in the formation of SO42- and NO3-. The correlations between NO3-, NO2 and
NO,NH4+ and NH3,SO42- and SO2 were significant at the confidence level of 0.01.
SO42- had negative correlation with SO2, and NO3- had positive correlation with
NO2. Compared with NH3, the NH4+ concentration was more obviously affected by
acid gases NO2, SO2.
PMID- 29965132
TI - [Pollution Characteristics of PCDD/Fs in Ambient Air and Exposure Risk Assessment
Around a Municipal Solid Waste Incinerator in Beijing].
AB - Ambient air was sampled and analyzed around a municipal solid waste incinerator
(MSWI) in Beijing from April 2014 to January 2015 to investigate the
concentrations, profiles and seasonal variations of PCDD/Fs in the region using
HRGC-HRMS technique. The mass concentrations and TEQ of 2,3,7,8-substituted
PCDD/Fs in the air samples ranged from 8.9 to 140 pg.m-3 and from 0.11 to 1.8
pg.m-3, respectively. The concentration values at 4 sampling sites in haze day in
autumn and all 7 sampling sites in winter were higher than the ambient air
standard of 0.6 pg.m-3 for dioxins regulated in Japan. 1,2,3,4,6,7,8-HpCDF and
OCDD dominated PCDD/Fs in all the samples for all four seasons with average
contribution fractions of 20.5% and 14.0%, respectively, while 2,3,4,7,8-PeCDF
was the dominant congener contributing to TEQ (43.3%). The spatial distribution
basically exhibited a trend that the concentrations at all sites were comparable
and not related to the distances from the source. Seasonal variation showed
obviously higher concentration in winter than the other three seasons, which may
attribute to the high concentration of ambient particulate matter due to domestic
heating and worse atmospheric dispersion that occurred in winter. The homologue
and congener profiles of PCDD/Fs in the air samples differed from those of the
flue gas emission from the MSWI, consistent with the principle component analysis
results. Dioxin inhalation exposure dose estimation showed that the dioxin
inhalation exposure risk of residents living in the studied area was at a
relatively safe level[0.060-0.224 pg.(kg.d)-1]. However, the dioxin inhalation
exposure risk in heavily polluted seasons still needs great concerns.
PMID- 29965133
TI - [Community Characteristics of Cultivable Bacteria in Fine Particles(PM2.5) of
Beijing and Baoding].
AB - Fine particles(PM2.5) collected by two middle volume air samplers in the suburbs
of Baoding and the urban area of Beijing during Jan 10th to 17th, 2015, were used
to compare the community characteristics of cultivable bacteria in the two sites.
In this study, we observed the particle morphology of PM2.5 using a field
emission scanning electron microscope (FESEM), analyzed the air mass
transportation source of the two sampling sites by the NOAA/ARL HYSPLIT-4
backward trajectory model, and measured the concentrations of the major water
soluble ions and heavy metal elements in the PM2.5 samples using ion
chromatography, continuous flow analyzer and ICP-MS. The results indicated that,
the cultivable bacteria of PM2.5 contained three phyla, which were Firmicutes,
Actinobacteria and alpha-Proteobacteria. Nine genera and 17 species of cultivable
airborne bacteria were isolated and identified. The most abundant phylum was
Firmicutes. The Gram-positive bacteria accounted for more than 90%. The spore
forming Bacillus which was the dominant species contributed 68.15% and 75% to the
total bacteria in urban Beijing and the suburbs of Baoding, respectively. The
difference in the community structure of PM2.5's cultivable bacteria in the two
sampling areas may be affected by PM2.5's physical and chemical properties and
air mass transportation.
PMID- 29965134
TI - [Emission Characteristics of Vehicle Exhaust in Artery and Collector Roads in
Nanjing Based on Real-time Traffic Data].
AB - The vehicle emissions were estimated by the Urban High Temporal-Spatial
Resolution Vehicle Emission Inventory Model and Decision Support System
(hereinafter referred to as the HTSVE system) with the real-time data including
traffic flow, average speed and fleet compositions obtained from Radio Frequency
Identification (RFID) and emission factors based on COPERT. The study focused on
the characteristics of vehicle emissions by means of non-parametric test and
cluster analysis with ArcGIS in artery roads and collector roads in Nanjing,
2014. The result showed that the proportion of passenger cars reached up to 80%,
and China 3 and China 4 accounted for over 90% while China 3 contributed most.
The daily average emissions in special periods including morning, noon and
evening were affected by both road types and weekend effect. The artery and
collector roads were classified as 5 clusters. Each type had similar emission
rates distribution and was affected by spatial position to support traffic
management.
PMID- 29965135
TI - [Catalytic Combustion of Soot Particulates over Rare Earth Pyrochlore Oxides
Doped with Transition Metals].
AB - Catalytic combustion is an efficient way to remove soot particulates from
automobile exhausts. A series of rare earth pyrochlore oxides La2Sn1.8TM0.2O7
(TM=Sn, Mn, Fe, Co, Cu) were prepared with CTAB-assisted sol-gel method. The
products were characterized by XRD,N2 Adsorption-Desorption, SEM, FT-IR, H2-TPR
and PL techniques. Their catalytic activity for soot oxidation was investigated
by TPO under tight conditions in both O2 and NO+O2 atmospheres. After calcination
at 900C, the as-synthesized oxides with pure pyrochlore phase displayed
nanospheres with diameter of 30-60 nm and relatively large surface areas. The
partial substitution of Sn with transition metals largely influenced the
reduction behavior of pyrochlores especially on the low temperature range in H2
TPR profiles, which was due to the interactions between Sn and transition metals.
The improved oxygen mobility might be derived from the structure defects induced
by transition metals doping, which could be helpful in oxidation reactions. In
comparison with uncatalyzed reactions, the La2Sn2O7 catalyst exhibited modest
catalytic activity for soot combustion, while transition metals incorporation
further enhanced the activity and selectivity. The improved activity of
transition metals doped samples was likely to be associated with the improved
reducibility and increased surface oxygen vacancies on the pyrochlore oxides. The
presence of NO in the gas phase significantly enhanced the soot oxidation
activity, which was due to the promotion effect of NO2. Especially, the densities
of active oxygen sites and turnover frequency (TOF) values of the catalysts,
quantified by isothermal anaerobic titration with soot as a probe molecule, were
used to explain the different soot combustion behaviors. Among the pyrochlore
oxides, the Co-doped pyrochlore sample displayed the highest ignition activity
and the largest intrinsic activity with TOF of 3.20*10-3 s-1.
PMID- 29965136
TI - [Water Quality Analysis of Beijing Segment of South-to-North Water Diversion
Middle Route Project].
AB - Water quality is the key problem that water management departments concern. Water
quality of Beijing segment of South-to-North Water Diversion Middle Route Project
is closely related to water security and social stability in Beijing. Since the
connection of Beijing part in Middle Route of South-to-North Diversion Project,
water quality data of Daning regulation and storage reservoir and Daning surge
tank was collected, and water quality indexes including water temperature, total
nitrogen, nitrate nitrogen, chloride ion, sulfate, dissolved oxygen, permanganate
index, pH, ammonia nitrogen, fluorine ion and total phosphorus, were monitored
monthly. With variance analysis, water quality difference among different water
sources of the South-to-North Water Diversion of Middle Route was analyzed. With
factor analysis method, the water quality risk factors of Daning regulation and
storage reservoir and Daning surge tank were identified. The results were as
following, water from Hebei province had higher contents of nitrate nitrogen,
total nitrogen, fluorine ion, chloride ion and sulfate than those of water from
Danjiangkou reservoir, but the water quality was not as good as that from
Danjiangkou reservoir. LSD difference test results showed that the dissolved
oxygen, nitrate nitrogen and total nitrogen of the water from Hebei province had
significant differences (P<0.05) between flood season and non-flood season, there
was significant difference (P<0.05) in pH of water from Danjiangkou reservoir
between flood season and non-flood season, and the water quality of Danjiangkou
reservoir was more stable than water from Heibei province. No matter in flood
season or non-flood season, there were no significant differences (P<0.05) in pH,
dissolved oxygen, permanganate index, total phosphorus and ammonia nitrogen
between the water from Danjiangkou reservoir and Heibei province, but there were
significant differences (P<0.05) in nitrate nitrogen, total nitrogen, fluorine
ion and sulfate ion and chloride ion. Contents of Nitrate nitrogen, total
nitrogen, sulfate and chloride ion in 2015 (the mixture of water from Hebei
province and Danjiangkou reservoir) in Daning regulation and storage reservoir
were lower than those in 2012-2014 (water from Hebei province), and the water
from Danjiangkou reservoir played a key role in dilution and adjustment of the
water from Hebei province in Daning regulation and storage reservoir. The water
quality differences test results between 2012-2014 and 2015 showed that there
were significant differences (P<0.05) in the nitrate nitrogen, total nitrogen,
fluorine ion, sulfate and chloride ion both in flood season and non-flood season,
and the water quality of 2015 was better than that of 2012~2014 in non-flood
season, but the differences of pH, dissolved oxygen, permanganate index, total
phosphorus, ammonia nitrogen were not obvious (P<0.05). The difference test
results between Daning regulation and storage reservoir and Daning surge tank
showed that Permanganate index, total nitrogen, fluorine ion, sulfate and
chloride ion had significant differences (P<0.05) both in flood season and non
flood season, and the contents of permanganate index, fluorine ion, sulfate and
chloride ions in Daning regulation and storage reservoir were higher than those
in Daning surge tank. The factor analysis results indicated that water quality
potential risk factors both in Daning regulation and storage reservoir and Daning
surge tank were mainly nitrogen, including ammonia nitrogen, nitrate nitrogen and
total nitrogen, and potential risk factors also included total phosphorus in
Daning regulation and storage reservoir.
PMID- 29965137
TI - [Hanfeng Pre-reservoir Commissioning Time Variation Feature of the Hydrology and
Water Quality in Three Gorges Reservoir].
AB - Hanfeng Pre-reservoir is very rare in the world which is specially designed to
reduce the impact of Fluctuating Zone, and it is formed in Hanfeng Lake of Three
Gorges reservoir. The Hanfeng Pre-reservoir has many special hydrological
characteristics and ecological environment features based on its unique "pre
reservoir" control mode, the wide seasonal wetland of Fluctuating Zone, the huge
life pollution and agricultural pollution, and the pressure of huge city and
excessive population. HanFeng Lake has a variety of morphological features such
as lakes, rivers, and other backwater bay, for the effect of water level
regulation in Three Gorges, since the successful commissioning of the Hanfeng
Lake pre-dam system in 2015. The change of Hanfeng Lake hydrology and water
quality during the commissioning was divided into four periods by combining
Hydrological and Morphological Variation characteristics with Water quality
indicators time clustering analysis:May to August as T1 (river period); January,
March and November to December as T2 (lake period); February, April and September
as T3 (water level fluctuation period); October as T4 (algal blooms period) in
2015. Principal component analysis and stepwise regression analysis showed that
Eutrophication of Hanfeng Lake was dominated by different dominant components at
different times and the water quality index factor which has a significant effect
on the Chl-a was also different. Cumulative contribution rates of principal
components were 82.93%, 77.61%, 78.32%, 88.40% for each period, respectively. The
main water quality indicators of T1 (river period) were DP, TP, SD, pH and the
significant influencing index of Chl-a was PC2, so Chl-a was mainly affected by
water nitrogen content. The main water quality indicators of T2 (lake period)
were TN, DN, DP, TP, NO3--N and the significant influencing index of Chl-a was
PC1, so Chl-a was mainly affected by water eutrophication including nitrogen and
phosphorus nutrient status. The main water quality indicators of T3 (water level
fluctuation period) were SD, NH4+-N, DN, T and the significant influencing index
of Chl-a was PC3. so Chl-a was mainly affected by water level fluctuation. The
main water quality indicators of T4 (algal blooms period) were TN, DN, DO, NH4+
N, pH, permanganate index, H, NO3--N and the significant influencing index of Chl
a was PC3. so Chl-a was mainly affected by flow rate and hydrodynamic conditions.
As mentioned in the review, the frequent and significant water level changes
during the commissioning of Hanfeng Lake were the important factors influencing
the change of hydrological and water quality characteristics.
PMID- 29965138
TI - [Modeling of Water Quality Response to Land-use Patterns in Taizi River Basin
Based on Partial Least Squares].
AB - Land use change in river basin is one of the most significant factors that
influence river water quality. Based on remote sensing images and river water
quality data of Taizi River Basin, partial least squares (PLS) model was applied
to explore the relationship between water quality and land use patterns at sub
watershed scale. In this study, PLS model was established by using the percentage
of area of land use patterns from seven different sub-watersheds as the variables
and the concentrations of four water quality parameters as the observations. The
established model was further tested with the data from other sub-watersheds in
Taizi River Basin. The results indicated that total nitrogen (TN) and nitrate
(NO3-) were significantly associated with land use types in Taizi River Basin
with determination coefficient (R2) greater than 0.62. As for chloride (Cl-) and
sulfate (SO42-), measured values and fitted values had a relatively low fitting
precision (R2<0.5), which meant land use pattern was not the main factor
affecting the concentrations of Cl-and SO42- in river water. Meanwhile, river
water quality had a strong correlation with the percentage of area of unused land
at the sub-basin scale (influence coefficient>0.24), although unused land area in
the Taizi river basin was small.
PMID- 29965139
TI - [Distribution Characteristics of Water Temperature and Water Quality of Fuxian
Lake During Thermal Stratification Period in Summer].
AB - In order to explore the distribution characteristics and change rule in daytime
of the water temperature and water quality of the deep plateau lake Fuxian Lake
during the thermal stratification period in summer, a typical point location was
selected respectively in the south, middle and north of Fuxian Lake in July 2014
to carry out investigation and observation after stratified sampling at each
point location and continuous stratified sampling of the point location in the
north during daytime. The result showed that 1The distribution of water
temperature of Fuxian Lake in summer had the temperature distribution
characteristics of deep lake during stratification period. The segment from the
surface to a depth of 15 meters was epilimnion with a range of 25.51-22.81C. The
segment from the depth of 15m to 40m was thermocline with a range of 22.81
14.72C. The segment below 40m was hypolimnion with a range of 14.72-13.70C. The
max temperature difference between the surface and the lakebed was 11.8C, which
was smaller than that of lakes in temperate zone during the same period. The
temperature of the lakebed was about 14C which was higher than that of the lakes
in temperate zone,which reflected the characteristics of water temperature
stratification of the deep plateau lake Fuxian Lake; 2The water temperature
stratification determined the characteristics of chemical stratification and the
ecological stratification:the pH, DO and conductivity presented the same layered
structure as the distribution of water temperature. What is noteworthy was that
the DO concentration of the lakebed was as low as 2-3mg.L-1. As an oligotrophic
lake, the DO became lower and lower at the lakebed of Fuxian Lake, which
indicated that it possibly faced ecological risks. Due to the separation of
thermocline, the nutritive salt accumulative effect appeared in the hypolimnion.
Chlorophyll a and permanganate index had a corresponding response relation with
the water temperature stratification and showed the max value at the upper layer
of the lake. 3During the thermal stratification period, the water temperature
stratification of Fuxian Lake had a change during daytime. The increased thermal
radiation in the noon caused the thermocline to dive, the strength to increase
and the depth to narrow, which significantly influenced the dynamic distribution
of pH, DO, conductivity and chlorophyll a of the epilimnion and the thermocline.
The change rule of TP, TN and permanganate index during the daytime was not
significant.
PMID- 29965140
TI - [Vertical Stratification Characteristics of Dissolved Oxygen and Phytoplankton in
Thousand-Island Lake and Their Influencing Factors].
AB - According to the data collected from the five monitoring sites in front of the
dam in Thousand-island Lake in September 2015, the vertical distribution
characteristics of dissolved oxygen (DO), water temperature, pH, turbidity,
conductivity and phytoplankton were analyzed. The influencing factors of special
stratification of DO and vertical distribution of phytoplankton were also
discussed. The results showed that:1 The vertical distribution of DO presented
"the surface is higher than the underlying" mode. DO ranged from 1.95 mg.L-1 to
8.25 mg.L-1 and the average concentration was 5.10 mg.L-1. Low-oxygen zones
appeared between 12 m and 20 m and the minimum concentration was 1.95 mg.L-1 at
17 m. The concentration of DO maintained at a high level between 0 m and 12 m and
the vertical variance was small. Sudden drop of DO occurred between 12 m and 20 m
and there was an anoxic zone (<4.0 mg.L-1). The concentration of DO returned to
normal level between 20 m and 38 m. Then it reduced under 38m as the water depth
increased. The vertical distribution of pH showed the same trend with that of DO
and their sudden change regions appeared in the same zone. 2 Vertical
phytoplankton biomass displayed significant difference. The phytoplankton biomass
of S1, S2 and S3 presented:mid-layer > surface > bottom. But S4, S5
presented:bottom > surface > mid-layer. In addition, the depth between 20 m and
30 m was the best for the growth of phytoplankton. 3 The correlation analysis
showed that DO and water temperature in the thermocline were significantly
correlative. The range and degree of low-oxygen zones in Thousand-island Lake was
determined by physical processes like thermal stratification of water and direct
or indirect effects of the plankton. Phytoplankton and DO, pH showed significant
negative correlation. The phytoplankton was mainly influenced by turbulent mixing
and DO stratification in the surface layer while it was mainly influenced by
light intensity at the bottom.
PMID- 29965141
TI - [Community Structure Characteristics of Eukaryotic Planktonic Algae in Liaohe
River Through High-throughput Sequencing].
AB - Eukaryotic phytoplankton plays an important ecological function in river
ecosystem. The 18S rRNA gene V4 variable region of the environmental samples in
Liaohe river was sequenced by using 454 pyrosequencing technology. The
reprehensive sequences of OTUs were annotated, and then the OTUs list was
compared to the species list obtained by microscope observation. The phylogenetic
tree was constructed based on the reprehensive sequences of OTUs and 18S rRNA
genes of eukaryotic phytoplankton algae obtained from GenBank. The community
structure characteristics of eukaryotic phytoplankton and its environmental
impact indicators were further studied. In this study, we got 167901 high-quality
sequences of 18S rRNA gene V4 region. These sequences were annotated to 424 OTUs,
including 134 eukaryotic algae. The results of the high-throughput sequencing
showed that bacillariophyta and chlorophyta were the dominant groups of the total
phyla. The high-throughput sequencing also revealed the presence of Charophyta,
Cryptophyta, Haptophyta and Chrysophyceae which were not observed by optical
microscope. The phylogeny analysis clustered the Cryptophyta and Pyrroptata at
phylum level. The different genera of Cryptophyta and part of families or genera
of Pyrroptata were clustered and distinguished by phylogeny analysis. The results
of RDA showed that NH4+-N, PO43-P and NO3- were the most important environmental
factors that affected the community structure. This study provided a new
perspective to understand the diversity, community structure and influence
factors of eukaryotic phytoplankton in Liaohe river. The study also indicated
that high-throughput sequencing has great application potential in investigation
of phytoplankton and the water environment quality assessment in Liaohe river.
PMID- 29965142
TI - [Effects of Coastal Organic Pollution on Bacterioplankton Community in Sanmen
Bay].
AB - Coastal organic pollution has become a serious problem, thus it is imperative to
assess the potential effects on the marine environment. The microbes are
generally the first responders to environmental perturbation, which may serve as
biological indicators for pollution levels. In this study, we collected surface
seawater samples from Sanmen Bay and adjacent Yushan Reserve. Using an Illumina
sequencing based analysis of bacterial 16S rRNA gene, we explored the effect of
organic pollution on the bacterioplankton community compositions (BCCs). The
results showed that the organic pollution (A) was 4.57+/-2.41 at Sanmen Bay,
which was significantly higher (P<0.001) than that in Yushan Reserve (0.43+/
0.74). The bacterial diversity and community compositions differed significantly
between the two locations. Specifically, the relative abundance of
Actinobacteria, alpha-Proteobacteria, beta-Proteobacteria, SAR406 in Sanmen Bay
was significantly higher than that in Yushan Reserve, while Bacteroidetes,
Cyanobacteria, Planctomycetes exhibited an opposite change pattern. A
multivariate regression tree analysis showed that the bacterial diversity was
primarily affected by water pH, organic pollution and chlorophyll a levels, which
respectively explained 27.7%, 15.6% and 6.7% variance in bacterial diversity. A
redundancy analysis (RDA) revealed that the bacterioplankton community was
significantly controlled by pH, salinity and organic pollution, which
cumulatively explained 14.8% of the variation in BCCs. In addition, the
geographic distance was significantly (P <0.001) correlated with BCCs, accounting
for 4.42% variance, which suggested that the spatial distribution of
bacterioplankton community was non-random. Moreover, this study screened 23
sensitive bacterial families, whose relative abundances were significantly
associated the organic pollution. For a given bacterial family, the change
pattern of relative abundance was consistent with its known function, thus
holding the potential for indicating organic pollution levels. To conclude, this
study showed that the increasing coastal organic pollution had altered BCCs, and
enriched the relative abundances of potential pathogens. Furthermore, the
sensitive bio-indicators were screened for evaluating the increasing organic
pollution level.
PMID- 29965143
TI - [Nitrate Source Identification and Nitrification-denitrification at the Sediment
water Interface].
AB - Identifying nitrate sources and its transformation mechanisms are important for
nitrate pollution control in surface water. The columnar core sediment samples in
West Lake were taken in different seasons. The transformation of nitrogen at the
sediment-water interface was studied using nitrogen and oxygen isotopes, stable
isotope analysis in R (SIAR) and acetylene inhibition method in the West Lake,
Hangzhou. The results showed that the concentration gradient of both NO3-and NH4+
existed at the sediment-water interface. NO3- concentrations decreased from
bottom water to pore water and NO3- was accumulated in sediments. NH4+
concentrations increased from bottom water to pore water and NH4+ was released
from sediments. Nitrate sources in bottom water where nitrification exited were
sewage (manure), soil nitrogen, chemical fertilizer and precipitation. Sewage
(manure) was the major nitrogen contributor (60.8%) in summer. Particularly high
delta15 N values in pore water indicated that there was strong denitrification at
the sediment-water interface in West Lake. The average nitrification rate and
denitrification rate at the sediment-water interface were 2.85 mmol.(m2.d)-1 and
23.51 MUmol.(m2.d)-1, respectively. The sediment-water interface played a role in
nitrogen removal process in aquatic environment. Seasonal and spatial variations
of nitrification rates and denitrification rates were found in this study.
Temperature and dissolved oxygen were the main influential factors for the
transformation of nitrogen at the sediment-water interface in West Lake.
PMID- 29965145
TI - [Pollution Characteristics and Risk Assessment of Heavy Metals from River Network
Sediment in Western Area of Taihu Lake].
AB - River sediments is a valuable environmental medium for characterizing
contamination of heavy metals in the western areas of Taihu Basin and the
associated risks to human health. We collected samples of typical inflow river
sediments from nineteen sites during different water periods. The results showed
that the concentrations of heavy metals in the river sediments followed the order
of Zn > Cr > Cu > Pb > Ni > As > Cd > Hg. Compared to the background
concentrations, the mean concentrations of Zn, Cd, Cu, Ni and Pb seriously
exceeded the standard values. Except for As, the highest concentrations of heavy
metals (Zn, Cr, Cu, Pb, Ni, Cd, Hg) were found in the samples from normal water
period. The metal (Cd) presented moderate pollution degree and ecological
risks,and the RI value of Cd accounted for about 47% of the total RI value. The
mPEC-Q values of the sediments were in the range of 0.12-0.76, and the mean value
was 0.3, indicating that the sediments in all of the sampling sites had a 15%-29%
probability of toxicity. In terms of the highest value of the heavy metals,
higher concentrations, Igeo, mPEC-Q and PCA values were found at the S2 sampling
sites. The results showed that effects of synergism of heavy metals pollutants on
the point were found in the paper, which will provide scientific basis for
control of heavy metal pollution in the Taihu Basin.
PMID- 29965144
TI - [Residues of Organochlorine Pesticides (OCPs) in Water and Sediments from Nansha
Mangrove Wetland].
AB - Mangrove wetland plays an important role in coastal environment. A total of 10
surface water samples and 7 surface sediments samples were collected in March,
2015 from Nansha mangrove wetland, and 8 compounds of organochlorine pesticides
(OCPs) were determined by GC-ECD to investigate residues level, source, and
ecological risk of these compounds in the study region. The result showed
concentrations of OCPs in water ranged from 1.89 to 90.19 ng.L-1 (mean 30.16 ng.L
1), and concentrations of OCPs in sediments varied from 3.10 to 16.02 ng.g-1
(average 8.58 ng.g-1). Compared with other estuaries and harbors around the
world, concentrations of OCPs in this study stayed at a median pollution level.
The mean values of distribution coefficient of HCHs and DDTs between water and
sediments were 857 and 368, respectively. Sediments in some parts of the area,
whose distribution coefficient was relatively high, may bring water the secondary
pollution. Source analysis indicated that HCHs mainly originated from the
application of Lindane, and DDTs originated from mixed sources of dicofol and
technical DDT. Compared with OCPs in water, OCPs in sediments might contain more
historical residual components. OCPs in water had light ecological risk, but OCPs
in sediments posed a potential high risk to mangrove ecosystem.
PMID- 29965146
TI - [Efficacy of Phoslock(r) on the Reduction of Sediment Phosphorus Release in West
Lake, Hangzhou, China].
AB - Famous as the world cultural heritage, West Lake in Hangzhou city has plenty of
soft sediments with high organic matter content. To search the countermeasures
for internal phosphorus release reduction from the sediment, the sediment core
incubation was conducted to understand the efficacy of Phoslock(r) on internal
phosphorus release in spring, summer and winter, respectively. The results showed
that the internal phosphorus release fluxes in winter and spring were relatively
low, with averaged values in the entire lake of 0.13 mg.(m2.d)-1 and 0.29
mg.(m2.d)-1, respectively, while the release flux was 3.29 mg.(m2.d)-1 in summer,
more than ten times higher than those in spring and winter. It was estimated that
23.7 kg of phosphorus could be released from sediment in the entire lake every
day in summer. Spatially, the phosphorus release flux was related to organic
matter contents in sediments, but not the phosphorus or bioavailable phosphorus
contents in sediments in West Lake. With Phoslock(r) added at the rate of 630 g.m
2, sediment phosphorus release was successfully controlled, which reduced the
phosphorus concentration in the lake water to less than 0.010 mg.L-1. Especially
during summer time, the sediment phosphorus release was reduced by 98% after
Phoslock(r) application. The research suggested that Phoslock(r) is powerful for
phosphorus control even for sediments with high organic matter content, which
could be considered in ecological restoration of WEst Lake.
PMID- 29965147
TI - [Identification and PAC Adsorption of Foulants Responsible for Irreversible
Fouling During Ultrafiltration of Dongjiang River Water].
AB - Foulants responsible for hydraulic irreversible fouling in Dongjiang River water
were identified by ultrafiltration process and their removal by powdered
activated carbon (PAC) adsorption treatment was investigated using fluorescent
excitation emission matrix and parallel factor analysis (EEM-PARAFAC). A
correlation analysis was then carried out for samples between the maximum
fluorescence intensities (Fmax) of three PARAFAC components after PAC adsorption
and the surface properties of corresponding PAC samples. The results showed that
two humic-like (C1 and C3) and one tryptophan-like fluorescent components were
obtained through PARAFAC analysis, in which tryptophan-like component C2 was
found to be the main substance in hydraulic irreversible foulants extracted from
fouled membrane. Furthermore, the results of correlation analysis suggested that
microspore area of PAC correlated with PAC adsorption of tryptophan-like
fluorescent components, which played an important role in irreversible fouling.
Both BET and mesopore+macropore area of PAC correlated with its adsorption of
humic-like fluorescent components. The result provided support for selecting PAC
in PAC-ultrafiltration hybrid process, which would be more effective for fouling
control.
PMID- 29965148
TI - [Efficiency and Kinetics of Triclosan Degradation in Aqueous Solution by
UV/Sodium Persulfate].
AB - UV activated sodium persulfate was employed to remove triclosan (TCS) in aqueous
solution. The effects of several factors such as UV wavelength,UV254
intensity,sodium persulfate dosage,pH value,and HA on TCS degradation were
investigated. The second-order rate constants of free radicals (.OH, SO4.-)
reacting with TCS and their contributions to TCS removal were
determined,respectively. The dominant free radical was also identified.
Furthermore, the TCS degradation efficiency in natural water by UV254/SPS and
UV254/H2O2 was compared. Finally,the possible pathway and intermediate products
of TCS degradation were analyzed with GC/MS. The results indicated that UV254
activated sodium persulfate could effectively remove TCS. The removal rate of TCS
could reach 98.15% within 100s under the conditions of UV wavelength of 254 nm,UV
intensity of 11.5MUW.cm-2,sodium persulfate dosage of 1mmol.L-1,and TCS initial
concentration of 275 MUg.L-1. TCS degradation followed the pseudo-first-order
kinetic model and the pseudo-first-order rate constant was determined to be
0.0392 s-1. Pseudo-first-order rate constant for TCS degradation increased with
the increase of UV254 intensity(I)and sodium persulfate dosage within experiment
ranges. The effect of UV wavelength on TCS removal was not notable. Neutral
condition was detrimental to TCS degradation. TCS removal was inhibited in the
presence of HA. The reaction rate constants for.OH and SO4.- reacting with TCS
were 7.62*109 L.mol-1.s-1 and 9.86*109 L.mol-1.s-1,respectively. SO4.- was the
dominant free radical and its contribution rate to TCS removal was 97.63% in
UV254/SPS system. The K value of UV254/SPS was 4.13 times higher than that of
UV254/H2O2 process,which demonstrated that UV254/SPS process could remove TCS
more effectively than UV254/H2O2. The main intermediate products found were 2,4
DCP and phenol in the degradation process of TCS in Milli-Q water by UV254/SPS.
PMID- 29965149
TI - [Influencing Factors on the Degradation of PFOS Through VUV-SO32].
AB - The objective of this experiment was to investigate the influence of SO32-dosage,
pH value, initial perfluorooctane sulfonate(PFOS)concentration as well as
coexisting substances on the degradation and defluorination of PFOS by VUV-SO32-
process. The results indicated that the increase of SO32- dosage could lead to
rise in the concentration of active species hydrated electron(eaq-) and thus
enhance the degradation and defluorination of PFOS. As the concentration of SO32-
increased from 1 mmol.L-1 to 20 mmol.L-1, the degradation and defluorination
rates of PFOS increased from 45% and 40% to 97% and 63%, respectively. The
degradation and defluorination of PFOS were also enhanced with the increment of
the solution pH values, and the defluorination was more sensitive to the pH
values. In addition, more PFOS was degraded with the increase of initial PFOS
mass concentration, although the degradation and defluorination rates of PFOS
were reduced. When the initial PFOS mass concentration changed from 1 mg.L-1 to
50 mg.L-1, the degradation amount of PFOS after four hrs increased by about 50
times, probably due to the higher utilization proportion of eaq- at high
pollutants concentration. Last but not least, the influence of co-existing
substances, Cl- and HCO3-, on PFOS degradation could be neglected, whereas their
effects on defluorination were observed. Defluorination of PFOS was enhanced with
the increased Cl- concentration, however, increased first and then decreased with
the increment of HCO3- concentration. It was also found that the presence of
humic acid(HA) lowered degradation as well as defluorination of PFOS owing to the
blockage of effective UV light and trapping of active species for photochemical
reaction.
PMID- 29965150
TI - [Simultaneous Photocatalytic Reduction of Cr(VI) and Oxidation of SSA by Carbon
Nitride].
AB - Carbon nitride is a novel nonmetal semiconductor photocatalyst, which has
developed into an ideal environmental treatment material in recent years.
Graphite carbon nitride(g-C3N4) was prepared through pyrolysis melamine, and the
structure, morphology and optical properties of samples were characterized by X
ray diffraction(XRD), transmission electron microscopy(TEM) and UV-Vis diffuse
reflectance spectra(UV-Vis DRS). The potential application of g-C3N4 in the
simultaneous photocatalysis reduction of Cr(VI) and oxidation of sulfosalicylic
acid(SSA) was further explored. And the effects of different conditions such as
catalyst dosage, pH and initial concentration ratio of Cr(VI) with SSA on the
simultaneous photocatalysis were also investigated. The results showed that when
the catalyst dosage was 0.5 g.L-1, pH=2, the initial concentration ratio of Cr
(VI) and SSA was 1:4(10 mg.L-1:40 mg.L-1), optimal simultaneous photocatalysis
efficiency was achieved, which was more than 3 times higher than that of the
separated photoreduction or photooxidation reactions. Within 3 hours, the
reduction ratio of Cr(VI) and oxidation ratio of SSA could reach 98.9% and 93.4%,
respectively. The mechanism of simultaneous photocatalysis was discussed. Cr(VI)
was reduced by electrons and SSA was oxidized by the combined function of hole,
O2.- and.OH under visible light.
PMID- 29965151
TI - [Modification of Diatomite by Zirconium and Its Performance in Phosphate Removal
from Water].
AB - Zirconium modified diatomite was obtained by modifying raw diatomite with
zirconium and the mass fraction of zirconia was 12.39% in the obtained material,
which was proved to be amorphous via XRD. SEM images showed that porous floccules
covered the surface of diatomite after modification and the specific surface area
of the zirconium modified diatomite was 75.22 m2.g-1, larger than that of raw
diatomite (14.00 m2.g-1). XPS spectra indicated that zirconia and diatomite were
bonded together through chemical linkage, rather than physical deposition. The
adsorption isotherm of phosphate by zirconium modified diatomite was fitted
better to the Langmuir model with a calculated maximum adsorption capacity
reaching 10.56 mg.g-1. The adsorption amount of zirconium oxide component in the
material was estimated to be 81.67 mg.g-1 ZrO2, which was higher than that of
pure zirconium oxides reported in previous studies. The adsorption amount of
phosphate by zirconium modified diatomite decreased with the increase of pH. The
adsorption was proved to be a ligand exchange process, supported by the XPS
spectra of Zr3d region before and after adsorption. Chloride ion, sulfate ion and
nitrate ion did not inhibit the adsorption of phosphate on the material, whereas
coexistence of bicarbonate ions competed with phosphate ions to a certain extent.
When treating eutrophic lake water with a phosphate concentration of 2 mg.L-1,
the phosphate concentration level could meet the III rank of Surface Water
Environment Quality Standard of China by adopting the dosage of zirconium
modified diatomite >=1.25 g.L-1.
PMID- 29965152
TI - [Reducing Effect of Three Disinfection Technologies for Sulfonamides Resistance
Genes].
AB - Antibiotic resistance genes (ARGs) in the environment have gradually engendered
extensive concern recently due to the harm caused to environment and human
beings. In this study, two sulfonamides resistant bacteria isolated from
secondary effluents of a municipal wastewater treatment plant were used to
compare the efficacy of three different disinfection processes (chlorination,
ultraviolet and ozone) in reducing sulfonamides resistance pollution using serial
dilution plate counting method and qPCR. The behavior characteristics of
sulfonamides resistance genes during the disinfection process were elucidated
using disinfection+DNaseI treatment. The results showed that all three
disinfection techniques could reduce the concentration of target bacteria, but
the abundance of sulfonamides resistance genes was still at a high level.
Furthermore, chlorination disinfection might reduce sulfonamides resistance genes
by reducing microbial biomass. Ultraviolet disinfection could damage genes
directly. However, during ozone disinfection, sulfonamides resistance genes would
escape to environment, and its potential environmental risks could not be
ignored.
PMID- 29965153
TI - [Removal of Estrogenic Effect by Typical Domestic Wastewater Treatment
Processes].
AB - Targeting at the characteristics of low concentration but high risk of endocrine
disrupting compounds in the aquatic environment, the current study investigated
the distribution of estrogenicity and E2 level using recombinant yeast estrogen
screen (YES) and enzyme linked immunosorbent assay (ELSIA) during domestic
wastewater treatment processes. The results showed that the levels of
estrogenicity and E2 in influents of wastewater treatment plants were 4.35-7.58
ng.L-1 and 36.95-83.43 ng.L-1, respectively. It was found that biological
treatment processes played a crucial role in the removal of estrogenicity and E2,
such as oxidation ditch, A2/O and A2/O followed by MBR, where the removal of
estrogenicity and E2 was 71.10%-75.54% and 75.88%-80.72%, respectively. The
activated sludge, with an estrogencity level of 1.84-2.43 ng.g-1 and an E2 level
of 8.45-12.84 ng.g-1, had the function of eliminating estrogenic effect to a
certain extent by adsorption. The estrogenic activity in the effluent of domestic
wastewater was 1.06-2.19 ng.L-1, which will pose potential risk to the aquatic
life in the environment. Last but not least, ELISA had a good correlation with
YES assay, which provides a new method for rapid screening and assessment of
water environmental estrogen.
PMID- 29965154
TI - [Effect of SRT on Stability of Yeast-SBR in Treating Oil-containing Wastewater].
AB - Sludge retention time(SRT) is a crucial parameter to influence the stability of
biological wastewater treatment systems. Especially, the effects of SRT on yeast
wastewater treatment remain unclear. In this study, mixtures of yeast strains
were applied to treat oil-containing wastewater in sequencing batch reactors(SBR)
and the effects of sludge retention time(SRT as 5, 10, 20, 40 d) on the removal
efficiency of pollutants, contents and composition of extracellular polymeric
substances(EPS), yeast cells settleability and yeast communities were
investigated. The results showed that the recommended SRT was 5-10 d for the
yeast-SBR system; Higher SRT led to decrease of COD removal rate and content of
EPS; the tightly-bounded EPS was the major one which consisted of
polysaccharides. SRT of 5-40 d had no significant effects on the SVI of yeast
cells, however, longer SRT (>20 d) resulted in the increase of mycelial cells and
a tendency to produce the filamentous bulking. In the continuous operation of
SBR, three extraneous yeast strains capable of utilizing or degrading oil were
identified in the systems under the short and long SRT. To conclude, shorter SRT
was favorable for the system stability in treating oil-containing wastewater by
yeasts.
PMID- 29965155
TI - [Degradation of the Disperse Dye Neocron Black(NB) by Biological Treatment].
AB - The biodegradation characteristics of the azo disperse dye neocron black (NB)
were investigated under aerobic, anaerobic and anaerobic/aerobic conditions
separately with the activated sludge system, and the biological degradation
process of the dye was analyzed by spectrophotometry and gas chromatography mass
spectrometry (GC-MS). The results showed that the degradation efficiency of NB
dye was the highest under fully aerobic conditions, followed by the
anaerobic/aerobic conditions, and fully anaerobic condition was the lowest. With
the increase of the concentration of NB dye, the dye and the intermediate
metabolite greatly decreased the microbial degradation efficiency of NB dye. The
addition of carbon source could not only promote the biodegradation of NB dye,
but also change the kinetic characteristics of the biodegradation process. The
spectrophotometry and GC-MS determination results showed that the chromophore was
completely degraded after biodegradation of NB dye. The intermediates metabolites
of NB dye included 2,4-Dinitroaniline, 2-cyano-4-nitro aniline, p-Nitroaniline
etc.
PMID- 29965156
TI - [Function of Polyphosphate Kinase Gene in Biological Phosphate Removal During the
Wastewater Treatment Process].
AB - This study aimed to identify the function of polyphosphate kinase gene (ppk) in
phosphorus removal. With the Red system, the target DNA with the homologous short
arms was amplified in the plasmid pKD4. Then the target DNA was transformed into
E. coli ATCC25922 which already had the suicide plasmid pKD46 by electroporation.
The plasmid pCP20 was transformed into the recombinant strains to delete the
kanamycin resistance gene. With the screening by negative resistance, together
with verification using positive and negative primers, the construction of ppk
gene deletion strain E. coli/ppk- Kan- was confirmed. The growth characteristics
of both the wild-type strain and the mutant strain were determined, and the
phosphate accumulating characteristics were compared when cultured in the
phosphate luxuriant medium after induced in the phosphate lacking medium. Also
the phosphate accumulating characteristics of the two strains were compared after
cultured in the anaerobic and aerobic alternating conditions for 5 times. The
results showed that the ppk deletion strain E. coli/ppk- Kan- was successfully
constructed. There was no growth difference between the mutant strain and the
wild-type strain. But in the first 4 hours of log phase, the mutant strain grew
faster than the wild-type strain. And 8h later, when both strains were in
stationary phase, the mutant strain grew slower than the wild type, indicating
that ppk affected the growth of the bacteria. Cultured in the phosphate lacking
medium and the phosphate luxuriant medium, the mutant strain's ability of
phosphate accumulating didn't decrease in spite of having no ppk gene. After 5
times induction, the amounts of phosphorus in both strains were about 1%-2%. The
phosphate amounts in the cells did not increase with increasing inducing times.
Polyphosphate or PHB was detected neither at anaerobic phase nor at the aerobic
phase. It indicated that the deletion of ppk did not affect the phosphorus
removal in wastewater treatment process, and the ppk gene did not show the
function of phosphorus removal.
PMID- 29965157
TI - [Short-cut Nitrification Recovery and Its Transformation into CANON Process in a
Biofilm Reactor].
AB - A short-cut nitrification process with modified polyethylene as carrier was
operated to investigate the biofilm short-cut nitrification recovery using
synthetic inorganic ammonia-rich wastewater as influent at 30C +/-1C. The short
cut nitrification was destroyed first by excessive aeration, and it was not built
in 83 days under the condition of continuous aeration with DO less than 0.5 mg.L
1 and free ammonia (FA) more than 1.5 mg.L-1, which are very beneficial to short
cut nitrification. However,short-cut nitrification was realized by changing
continuous aeration to intermittent aeration on 84th day, and it was proved again
on 142nd day. After that, biofilm system provided a living environment for
ANAMMOX bacteria, anaerobic ammonia oxidation occurred, and the biofilm short-cut
nitrification process was gradually transformed into CANON process. As the load
of influent and aeration increased, the total nitrogen removal efficiency and
removal load increased, and the total nitrogen removal load could reach up to
2.52 kg.(m3.d)-1. Finally, in the 3rd stage, DeltaNO3--N/DeltaTN was 0.10 on
average, which means stabe short-cut nitrification in the CANON process.
Therefore, once NOB was adapted to FA, it would be not very easy to recover short
cut nitrification, while intermittent aeration was an effective way, and the
nitriation process would be finally transformed into CANON process, which would
further improve the short-cut nitrification stability.
PMID- 29965158
TI - [Nitrogen Removal Characteristics and Diversity of Microbial Community in ANAMMOX
Reactor].
AB - The volume loading of upflow blanket filter increased from 0.52 kg.(m3.d)-1to
2.75 kg.(m3.d)-1 by improving the influent NH4+-N and NO2--N concentrations. The
removal efficiency of NH4+-N, NO2--N and TN increased from 76.18%, 53.47%, 55.66%
to 94.04%, 86.97%, 82.96% respectively. Meanwhile, the microbial community of UBF
ANAMMOX reactor was analyzed by Illumina high-throughput sequencing during the
initial and later operational process. The results indicated that the
denitrifying bacteria coexisted in the reactor. The percentages of
Planctomycetes, Proteobacteria and Nitrospirae in the sludge were 27.9%-39.9%,
1.1%-26.4% and 0.035%-0.188%, respectively. The proportions of Planctomycetes and
Proteobacteria increased from 1.1%, 27.9% in the enrichment stage to 26.4%, 39.9%
in the stable operation stage respectively. In addition, Planctomycetes increased
significantly. The proportion of Brocadiacea reached 24.57%. Therefore,
Brocadiacea became the dominant bacteria in the phylum Planctomycete, which
contained Candidatus brocadia. The alpha diversity index and relative abundance
of clustering figure indicated that the diversity of microbial community
decreased gradually and the structure of microbial community changed obviously.
PMID- 29965159
TI - [Effect of Environment Adjustment Layers on Nitrogen Transformation in Anaerobic
Bioreactor Landfills].
AB - To investigate the perennial effect of environment adjustment layers on the
interior environment and nitrogen transformation in anaerobic bioreactor
landfills, three sets of simulated anaerobic bioreactor landfills and two kinds
of environment adjustment layers of mineralized refuse with heavy calcium
carbonate (R2) and mineralized refuse with natural zeolites (R3) were designed
and established. The degradation and transformation of nitrogen in waste and
leachate had been monitored for 390 days. The results showed that, the value
orders of pH, alkalinity, oxidation reduction potential and moisture content (MS)
were pH(R2) > pH(R3) > pH(R1), alkalinity (R2) > alkalinity (R3) > alkalinity
(R1), Eh(R2) < Eh(R3) < Eh(R1) and MS(R3) > MS(R2) > MS(R1). In R1, R2 and R3,
the degradation rates of total nitrogen, ammonia nitrogen, nitrate nitrogen in
waste were 79.2%, 82.3% and 88.5%, 48.3%, 60.1% and 67.7%, 38.5%, 44.2% and
53.4%, respectively. Concentration comparison results of total nitrogen, ammonia
nitrogen and nitrate nitrogen in leachate were TN(R3) < TN(R2) < TN(R1),NH4+
N(R3) < NH4+-N(R1) < NH4+-N(R2)NO3--N(R3) < NO3--N(R2) < NO3--N(R1).
Additionally, both of mineralized refuse with heavy calcium carbonate and
mineralized refuse with natural zeolites could long-term adjust and optimize the
interior environment of anaerobic bioreactor landfills for the degradation and
conversion of nitrogen. Mineralized waste with natural zeolite could not only
promote the degradation and transformation of nitrogen components in waste and
leachate, but also control the accumulation of ammonia nitrogen through leachate
recirculation.
PMID- 29965160
TI - [Characteristics of Anaerobic Methane Removal Coupled to Fe(III) Reduction in
Aged Refuse].
AB - Landfills are the third largest iron reservoir and one of the largest sources of
methane release. Iron, as a kind of transition metal, plays a particularly
important role in environmental biogeochemistry and is closely linked to the
biogeochemical cycle of C, S and N. The aged refuse could be utilized as bio
cover material to improve the removal of contaminants. Therefore, this work
investigated the effect of iron reduction on anaerobic removal of methane, and
the interactions of ferric iron with nitrate and sulfate in the aged refuse. The
columns were operated as landfill bio-covers and recirculated leachate with
addition of FeCl3 solution. In the experiment, three columns were used, two of
them were used as controls (named as B1 and B3), B1 was fed with leachate and
CH4, whereas B3 was only recirculated with leachate adding FeCl3. The treatment
B2 was fed with the above two substrates. During the operation of columns, the
contents of CH4, CO2 and N2 in the gas, and the concentrations of NO3-, NO2-,
NH4+, SO42-, Fe(III) and Fe(II) in the leachate and refuse were respectively
determined. The results showed that adding ferric iron obviously enhanced the
removal of methane in anaerobic aged refuse, the decrease of methane content with
time obeyed zero-order kinetic, and the rate of methane removal(denoted as
CH4/aged refuse)reached 1.28 mmol.(kg.d)-1. In the anaerobic condition, methane
could improve the reduction of Fe(III) to dissolved, active and bioavailable
Fe(II). The active Fe(II) probably coupled to the transformation of NO3- and SO42
, and thus accelerated the removal of NO3- and SO42-.
PMID- 29965161
TI - [Assessment of Heavy Metal Pollution and Tracing Sources by Pb & Sr Isotope in
the Soil Profile of Woodland in Quanzhou].
AB - The contents of 8 heavy metal elements (Sr, Ni, Fe, Cr, Cu, Mn, Pb, Zn) and the
lead & strontium isotope composition of soil profile of woodland in Quanzhou city
were analyzed by AAS and ICP-MS, respectively. A modified BCR four-step
sequential extraction procedure was carried out to obtain the speciation
fractionation of heavy metals in the soil profile from 4 stations. The results of
the heavy metal elements and the speciation fractionation of heavy metals in the
soil profile showed that the heavy metal pollution in the woodland in Quanzhou
was relatively light, and the main pollution factor was Sr. The non-residue state
of Pb was the highest, leading to the highest activity. The result of Nemero
comprehensive pollution index showed that Sr in the depth of 0-60 cm was at heavy
pollution level. The results of the RSP showed that the activity of Pb was the
highest. The results of EF showed that Pb, Sr, Mn and Zn had exogenous sources.
Factor analysis showed that the main sources of heavy metals were the compound
pollution of agricultural activities, natural resources, and the vehicle exhaust.
Composition of Pb isotopic ratios showed that, Pb in soil profile of woodland in
Quanzhou was from vehicle exhaust and parent material. The contribution rates of
the two sources in the soil profile were calculated by using the two-mixed model.
The contribution rates of parent material and vehicle exhaust were 85.14%(62.53%
98.36%) and 14.86%(1.640%-37.47%) on average, respectively. Strontium isotope
tracing results showed that the main sources of strontium were also vehicle
exhaust and parent material. Coupling both Pb and Sr isotope ratios agreed with
the above mentioned results.
PMID- 29965162
TI - [Accumulation and Migration Characteristics in Soil Profiles and Bioavailability
of Heavy Metals from Livestock Manure].
AB - The long term and high dosage application of livestock manure may result in heavy
metal accumulation and migration in the soil, which may endanger food security
and affect the top soil heavy metal environmental capacity. Thus, one of the most
important tasks for prevention of soil heavy metal pollution is scientific
determination of the safe use load of heavy metals in livestock manure. A 4-year
field plot experiment was carried out to quantitatively study the accumulation
and migration characteristics of heavy metals from pig and chicken manure in soil
profiles and the differences of bioavailability. The results showed that the
contents of Cu and Cd increased significantly by 43.8%-118.6% and 28.2%-44.9% in
topsoil(0-15 cm) after 4-consecutive year application of pig manure, and the
contents of Cu, Zn, Cd, Cr, As, Pb also increased by 29.7%-48.5%, 239%-456%,
19.9%-80.8%, 40.4%-163%,11.8%-22.0% and 80.3%~95.0% obviously after application
of chicken manure. The accumulation rates of Cu and Zn in topsoil were 76.4%-119%
and 14.2%-20.4% with pig manure, 72.1%-88.7% and 63.9%-78.9% with chicken manure.
Under a high dosage of pig and chicken manure, Cu and Zn migrated to a deeper
soil evidently. Applying 60 t.hm-2 of pig manure after 4-consecutive year, Cu
could migrate to 15-30 cm soil layer, Zn migrated to 30-60 cm soil layer with
chicken manure. Except topsoil, the contents of Cr, Cd, As, Pb did not
significantly increase in other soil layers. 4-year continuous application of
chicken manure significantly decreased the contents of Cu and Cd, but increased
the contents of Zn and Cr in wheat grain and the content of Zn in wheat straw.
Pig manure significantly decreased the content of Zn in wheat grain, but
increased As content with 60 t.hm-2, the contents of Cu and As in wheat straw
also increased significantly. Besides, the cumulative rate of heavy metals in
wheat was no more than 6%, wheat grain carried out more Cu, Zn than straw, but
the Cd, Cr, As, Pb were opposite. The cumulative rate of heavy metals in wheat
decreased with the increasing application of manure. This research has an
important significance in scientific determination of the heavy metal loads of
plow layer, ensuring the quality and safety of agricultural production, and
providing a scientific basis for the source control of soil heavy metal pollution
and the safety production of agricultural goods.
PMID- 29965163
TI - [Pollution Characteristics and Source Analysis of Polycyclic Aromatic
Hydrocarbons in Agricultural Soils from Shandong].
AB - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants
that originate mainly from anthropogenic sources. PAHs have elicited much concern
because they exhibit strong toxic, carcinogenic, and mutagenic properties.
Agricultural soil is at risk of PAH contamination mainly caused by atmospheric
depositions, wastewater irrigation, or organic substances and biowaste applied as
fertilizers. The surface agricultural soils were collected from Shandong in July
2015, and measured for 16 US EPA priority PAHs using high performance liquid
chromatography with UV and fluorescence detector. The content and composition of
PAHs were analyzed. The differences of PAHs between soils from the field for
growing crops and from vegetable greenhouses, and between soils from point
sources and from non-point sources were compared. The sources of PAHs were
determined with methods of ratio between PAHs and positive matrix factorization
(PMF), and the risks of PAHs were assessed. The results showed that the total
content of 16 PAHs (?16PAHs) ranged from 111.5 ng.g-1 to 2744.1 ng.g-1, with the
mean of 556.3 ng.g-1. The content of 3-ring PAHs was relatively high, with the
mean of 201.5 ng.g-1; while the contents of 2-ring and 6-ring PAHs were
relatively low, with the mean of 39.3 ng.g-1 and 43.4 ng.g-1, respectively.
According to the contamination classification in Poland, 71% of the samples in
Shangdong were weakly contaminated. Compared with other areas in China, the
content of PAHs in the agricultural soils in Shandong was in the middle range.
Acenaphthene, fluorine, and fluoranthene were the major PAH compounds, accounting
for more than 10% of the total PAHs; while the contribution of indeno (1,2,3-cd)
pyrene was low. The content of ?16PAHs and contribution of 7 carcinogenic PAHs
were significantly higher in soils polluted by point sources than those in soils
from non-point sources. Moreover, the contribution of PAHs with 2-3 rings was
significantly higher in soils from non-point sources, while the contribution of
PAHs with 4-6 rings was significantly higher in soils polluted by point sources.
There was no significant difference in soils from vegetable greenhouses and from
adjacent field soils, and the contribution of PAHs with 3-4 rings was high. The
PAH isomer pair ratios of Ant/(Ant+Phe), Flu/(Flu+Pyr), BaA/(BaA+Chr), and
InP/(InP+BP) were utilized as molecular indices to elucidate the possible PAH
sources, and the results suggested that the PAHs in the soils were mainly from
combustion. To quantitatively assess the contribution of various sources to PAH
contamination, PMF was used to analyze the sources. The sources of PAHs were
combustion of coal biomass, oil combustion from traffic, coking, and petroleum
pollution, with contribution of 42.7%, 19.3%, 22.8% and 15.2%, respectively.
Toxic equivalency factors were used to evaluate PAH contamination in the soils,
and the carcinogenicity of other PAHs relative to BaP was quantified to estimate
the BaP-equivalent concentration (TEQBaP). The TEQBaPof 16 PAHs (?16TEQBap) in
soils from non-point sources and vegetable greenhouses was 31.69 and 44.47 ng.g
1, respectively, which were below the safe value in Canadian soil quality
guidelines. However, the ?16TEQBap in some field soils from point sources
exceeded the safe value, indicating that there were potential risks in the soils
from point sources in Shandong.
PMID- 29965164
TI - [Distribution Characteristics and Influencing Factors of Organophosphorus
Pesticides in Typical Soil Environment of Jianghan Plain].
AB - In order to study the distribution characteristics of organophosphorus pesticides
(OPPs)in the soil of Jianghan plain,78 profile-soil samples from various depth
and 7 surface-soil samples were collected in September,2015 in established
groundwater monitoring field site, Jianghan plain. The OPPs concentrations were
determined by gas chromatography with nitrogen-phosphorus detector(GC-NPD). The
results showed that OPPs were widespread in our studied area. The OPPs
concentrations of suface-soil samples ranged from 89.80 ng.g-1 to 193.85 ng.g
1,with an average of 140.05 ng.g-1, whereas the OPPs concentrations of profile
soil samples ranged from 19.81 ng.g-1 to 138.28 ng.g-1,with an average of 40.99
ng.g-1. The main ingredients of OPPs in surface and profile soil samples were
methamidophos, omethoate, diazinon and quinalphos,and the residual amount of 10
kinds of OPPs had posed a threat to agricultural products according to the
America soil pesticide residue limits standards. The horizontal distribution of
OPPs concentration in profile soil followed the order of nearby river farm area >
nearby river area > farm area, namely GS1-1 > GS4 > GS2 > GS3. while the vertical
distribution mostly decreased at first and then increased with increasing depth.
The distribution characteristics of OPPs were also influenced by many factors,
such as application amount of OPPs, the adsorption and desorption actions of
soil, vertical movement of groundwater, the terrain environment in the study
area, and the concentration of soil organic matters.
PMID- 29965165
TI - [Characteristics and Influencing Factors of Biologically-based Phosphorus
Fractions in the Farmland Soil].
AB - A suitable fractionation method of phosphorus (P) is a key to effective
assessment of soil P componential features. Here a new biologically-based P (BBP)
method was used to evaluate the P fractions in the upland and paddy soils across
large-scale area in China. The soil P was divided into four components:1 soluble
or rhizosphere-intercepted (CaCl2-P), 2 organic acid activated and inorganic
weakly bound (Citrate-P), 3 enzyme mineralization of organic P (Enzyme-P), 4
potential activation of inorganic P (HCl-P). Then, the relationships between
biologically-based P fractions and standard Olsen-P were investigated, and
driving factors of P fractions were identified. The results showed that P content
was in order of HCl-P>Citrate-P>Enzyme-P>CaCl2-P. All P components of upland soil
displayed higher levels than those of paddy soil. Moreover, the P components were
highly positively correlated with the Olsen-P, suggesting that each P component
contributed to soil P availability. However, it was found that Olsen-P was most
highly correlated with CaCl2-P and Enzyme-P (R2=0.359; R2=0.386) in upland soil,
while Olsen-P was most highly with Citrate-P (R2=0.788) in paddy soil. This
result indicated that available P of upland soil was mainly from organic P
mineralization and soluble P, and available P in paddy soil was mainly from
inorganic P activation. Redundancy analysis (RDA) showed that the P components
were mainly affected by soil pH and silt content, which suggested that it could
enhance the P availability via regulating soil pH in the agricultural activities.
PMID- 29965166
TI - [Effect of Straw Application on the Dynamics of Exogenous Nitrogen and Microbial
Activity in Paddy Soil].
AB - Returning straw to the field provides an important source of fertilizer that can
increase soil fertility. However, the rate of straw carbon utilization is low and
large amounts of greenhouse gases are emitted due to the high carbon to nitrogen
ratio of the straw mass. In this regard, the application of inorganic nitrogen
and phosphate fertilizers can control the ratio of elements in the soil, increase
the activity of microorganisms and their utilization of elements, and promote the
improvement of soil fertility. In this study, straw application conditions were
simulated, and inorganic nitrogen fertilizer labeled with 15N was added to
examine the effects of different nutrient fertilizer additions on the
transformation and distribution of exogenous nitrogen in the soil, and also the
characteristics of the microbial response. The results showed that application of
straw increased the contents of ammonia nitrogen and total nitrogen in the soil
and soil solution. When both straw and inorganic nitrogen fertilizer were
applied, the 15N-TN in the soil remained at 28 to 33 MUg during the 100-day
culture phase. In contrast, 15N-NH4+ increased gradually during the initial 30
days of the culture phase, but subsequently decreased gradually. Application of
phosphate increased the contents of 15N-TN and 15N-NH4+ in the soil, but
decreased the content of 15N in the soil solution by 28%. The distribution of
inorganic nitrogen in the soil showed that the proportion of 15N in the soil
remained at 52%-61%. Addition of phosphate fertilizer increased the distribution
ratio of 15N in the soil by up to 16.5%, whereas the proportion of 15N in the
soil solution decreased from 36% on the fifth day to 30% on the 100th day,
thereby the loss amount of 15N reduced by 1.2-fold. Addition of straw promoted
microbial activity and significantly increased the microbial biomass nitrogen
(MBN) content of the soil. Addition of inorganic fertilizer further promoted the
microbial activity of the soil. After the 100-day culture experiment, the
addition of straw, inorganic nitrogen, and phosphate fertilizer increased MBN to
between 2.0-fold and 2.2-fold that of the control treatments. Addition of
phosphate fertilizer increased the utilization of 15N by microorganisms, so that
the amount of 15N-MBN was 1.5-fold higher than that of treatments where only
straw and nitrogen fertilizer were added. Examination of soil enzyme activity
showed that nitrogen fertilizer reduced soil enzyme activity and substrate
affinity. When both nitrogen and phosphate fertilizers were added, the enzyme
activity was 48.1% higher than that when only straw was added. The findings of
this study thus provide a theoretical basis for furthering our understanding on
the nitrogen cycle of the paddy soil ecosystem, the improvement of soil
fertility, and the reduction of greenhouse gas emissions.
PMID- 29965167
TI - [Effects of Biochar on Surface Albedo and Soil Respiration in Suburban
Agricultural Soil].
AB - Biochar application to soils is currently considered as a means of mitigating
climate change by sequestering C, which withdraws CO2 from the atmosphere and
consequently influences the trend of global climate change. However, only a few
studies have been done on surface albedo variations on farmland, it might be true
that the application of biochar to soil could induce a radiative forcing by
changing the surface albedo. Based on this background, this study aiming at the
characterization of seasonal changes in albedo on the farmland both with plants
and without plants, and its effect on soil temperature, soil moisture, soil
respiration and soil organic carbon fractions. There were 3 major treatments in
the experiment with 3 repetition of each major treatment, namely, CK (the control
treatment), BC0.5 (biochar applied at 0.5 kg.(m2.a)-1) and BC4.5 (biochar applied
at 4.5 kg.(m2.a)-1). Each major treatment contained 2 sub-treatments, which were
crop cultivation (+) and non-cultivation (-). The experiment results showed that
in the early stage of crop growth (maize seedling stage to jointing stage, wheat
seedling stage to winter period), the surface albedo of BC4.5+and
BC0.5+significantly decreased compared with CK +(P<0.05). The biggest surface
albedo decline rates of BC4.5 + and BC0.5 + in winter wheat season were 23.7%,
17.9% and 44.5%, 44.9% in summer maize season. The leaf area index of each
treatment was remarkably correlated with the surface albedo. The shadow produced
by the development of crop canopy structure would cover the change of surface
color induced by the input of biochar. Under the condition of bare land, the
surface albedo of biochar treatment was significantly decreased compared with the
control treatment(P<0.05). Compared with the control treatments, the soil CO2
flux of the biochar treatments was significantly increased(P<0.05). With the
extension of time, the growth rate of soil CO2 flux of biochar treatment was
decreased gradually. The increase from BC4.5 + to CK + was gradually reduced from
276.7% to 36.1%, and the increase of BC4.5-from to CK-was significantly reduced
from 163.5% to 39.8%. The increase of soil CO2 flux could be derived from the
mineralization of the readily decomposed carbon fractions in the biochar-soil
system. The decrease of surface albedo caused by the input of biochar had no
direct effect on soil respiration, and the input of biochar could reduce the
temperature sensitivity of soil respiration. This result could provide a
foundation for the verification of the chemical and biological stability of
biochar.
PMID- 29965168
TI - [N2O Consumption Ability of Submerged Paddy Soil and the Regulatory Mechanism].
AB - A large number of researches showed that the N2O negative emissions from flooding
paddy fields, peatlands and other wetlands ecosystem were frequent and
considerable, which is of great significance on alleviating the greenhouse gas
effect. However, there are few reports about the transformation and microbial
mechanism of N2O between atmosphere and paddy soil. The slurry of surface paddy
soil (0-5 cm) was incubated in laboratory conditions, and the effect of enhanced
N2O concentrations in headspace on the N2O consumption capacity of submerged
paddy soil and the response of nosZ gene abundance were explored. The results
showed that, paddy soil under flooding and anaerobic conditions harbored very
strong potential of N2O reduction along with a relatively high nosZ gene
abundance (108 copies.g-1 dry soil at DNA level). Regression analysis presented
the N2O concentrations in headspace were positively correlated (r2=1, P<0.001) to
the N2O consumption rates of paddy soil slurry, indicating the high N2O
concentration could stimulate the N2O consumption power, to a very high rate of
4567.99 MUg.(m2.h)-1. Meanwhile, there were no significant differences in the
high abundance of nosZ gene among N2O treatments, demonstrating the nosZ gene
abundance at DNA level might not be the main controller of N2O consumption
ability in submerged paddy soil and further study on the key microbial factor is
needed.
PMID- 29965169
TI - [Non-CO2 Greenhouse Gas Release from Different Biological Wastewater Treatment
Processes].
AB - Methane (CH4) and nitrous oxide (N2O) are two of the most important non-CO2
greenhouse gases. And municipal sewage treatment plant is an important
anthropogenic source of CH4 and N2O. Therefore, it is essential to measure the
production and emission of CH4 and N2O during biological wastewater treatment
process. The surface emission flux isolation chamber was employed to collect the
gas sample from the Xi'an No.3 WWTP (the Orbal oxidation ditch process) and Xi'an
NO.4 WWTP (A/A/O process) to determine the contents of methane and nitrous oxide.
And the effects of temperature and dissolved oxygen concentration on non-CO2
greenhouse gases emission from Xi'an NO.4 WWTP were discussed. The results showed
that methane and nitrous oxide emission factors from No.3 WWTP were 1181 mg CH4
per m3 influent and 36.20 mg N2O per m3 influent, respectively while those from
the No.4 WWTP were 209 mg CH4 per m3 influent and 54.64 mg N2O per m3 influent.
In addition, the important influencing factors which affected methane and nitrous
oxide emission were temperature, aeration strategy, DO, nitrite oxidation rate
and specific methanogenic activity.
PMID- 29965170
TI - [Effect of Application of Sewage Sludge Composts on Greenhouse Gas Emissions in
Soil].
AB - Effect of application of sewage sludge compost on the emission of greenhouse gas
from soil was investigated by analyzing the dynamic characteristics and emission
factor of CO2, CH4 and N2O in soil after spiking two different composts
(A:compost with biochar, B:compost without biochar) with varying fertilizing
amount into soil. The results indicated that emissions of CO2 and CH4 mainly
occurred in the plant growth period with low fertilizer amount of biomass
charcoal compost reducing CO2 emissions, and high application content increasing
CO2 emissions. CH4 emission fluxes showed negative values, indicating that soil
could adsorb CH4, and the adsorbing amount for control was significantly higher
than those for other treatments (P<0.01). The absorbing amount in treatment A
increased with the fertilizing amount (P<0.05). N2O emissions mainly occurred at
the germination and seedling stages, and emission fluxes increased with the
fertilizing amount (P<0.01). N2O was considered as the main generated greenhouse
gas during agricultural process with sludge compost, and its emission factor from
sludge compost soil was 1.02%-1.90% (A compost) and 1.28%-2.93% (B compost),
respectively. Biochar could significantly reduce the carbon emission, as the
total greenhouse gas released from soil with biochar compost was 19.49% to 35.56%
less than that in soil without biochar, which was more obvious for N2O emission
reduction (compared with CH4 mitigation).
PMID- 29965171
TI - [Effect of Nano Zeolites on pH, CEC in Soil and Cd Fractions in Plant and Soil at
Different Cadmium Levels].
AB - Soil incubation experiment and pot experiment were carried out to investigate the
influence of nano zeolite (NZ) and ordinary zeolite (OZ) on the soil pH, cation
exchange capacity, concentration of soil Cd, soil Cd fraction and Cd uptake by
Chinese cabbage when exposed to different Cd pollution levels(1, 5, 10 and 15
mg.kg-1). The results of soil incubation experiment showed that the nano zeolite
and ordinary zeolite dose(5, 10 and 20 g.kg-1) increased the soil pH and cation
exchange capacity, and decreased the concentration of soil exchangeable Cd, while
increased the concentration of Cd in carbonate, Fe-Mn oxide, organic matter and
residual fraction. The lowest EX-Cd was observed in the high nano zeolite (20
g.kg-1) treatment. The soil pH and cation exchange capacity was extremely
negatively correlated with the concentration of soil exchangeable Cd(P<0.01),and
extremely positively correlated with the concentration of soil Fe-Mn oxide
Cd(P<0.01). The results of pot experiment showed that the FDC of exchangeable Cd
in soil decreased by 6.4%-63.2%, and the FDC of water-extractable and ethnol
extractable Cd in Chinese cabbage decreased by 2.1%-56% and 11.8%-100% with
zeolite application, respectively. Moreover, the reduction effect of nano zeolite
on Cd concentration in soil and plant was better than that of ordinary zeolite.
The FDC of Cd fraction in shoot of Chinese cabbage showed correlation with the
FDC of carbonate Cd and organic matter Cd in soil(P<0.05) when exposed to 1 mg.kg
1 Cd pollution. Moreover, correlation was also found in the FDC of organic matter
Cd and residual Cd in soil(P<0.05) under 5 mg.kg-1 Cd pollution.
PMID- 29965172
TI - [Dynamic Differences of Uptake and Translocation of Exogenous Selenium by
Different Crops and Its Mechanism].
AB - The study aimed to find out the dynamic changes of selenium (Se) uptake with
crops growing and to provide better understanding on the translocation of Se in
soil-plant system. Pot experiments and laboratory analysis were carried out, in
which 6 crops were planted for eight weeks in the soils treated with selenite and
selenate. The results showed that there was a significant difference in the plant
dynamic uptake pattern for selenite and selenate. Se concentration in shoots and
roots of all tested plants continuously declined with growth since the third week
after planting for selenate treatment; while Se concentration in roots of plants
gradually increased with the growth, and that for shoots firstly increased and
then leveled off or decreased for selenite treatment. Crops could accumulate Se
throughout the whole growing period, while 80% of the Se in plants was uptaken in
the first 6 weeks. Among the 6 tested plants, the Se concentration in the shoots
and roots of mustard was the highest, followed by the shoots of wheat for
selenate treatment. The Se concentration in shoots of carrot was the highest,
while that in roots was the lowest for selenite treatment. For the same Se
treatment, the Se concentrations in both roots and shoots of broccoli, purple
cabbage and flowering Chinese cabbage were similar. Broccoli, purple cabbage,
flowering Chinese cabbage, mustard and wheat had higher translocation ability to
transport selenate than selenite from roots to shoots, whereas carrot had the
same ability for translocating selenite and selenate. Biological dilution
affected the dynamic changes of the Se content in crops, especially for selenate
treatment, and a significant negative correlation between Se concentration of
plants and their biomass further verified this. However, the changes of biomass
of plants with growing period couldn't explain the total inverse dynamic uptake
pattern for selenite and selenate. A significant positive correlation was
observed between Se accumulations amount in six crops with available Se changes
in soil during the corresponding growing period for selenate treatment, while no
such correlation was found for selenite treatment. Se accumulation in crops grown
on selenite-treated soil accounted for 0.5%-18.1% of soil available Se, whereas
that in selenate treatment was 1.1-4.5 times of soil available Se except for
carrot. In conclusion, the dynamic changes of Se uptake with crop growth were the
comprehensive results of the absorption and transport capacity of crops, Se
availability in soil and biological dilution. It should be considered as a whole
in the selenium biofortification.
PMID- 29965174
TI - [Forms Distribution and Ecotoxicity of Three Forms of Sulfonamides in Root-Soil
Interface of Maize].
AB - Forms distribution and ecotoxicity of sulfonamides in root-soil interface of
maize were studied by chemical analysis and luminescent bacteria toxicity assay.
The results indicated that the water soluble residues were the main form in
rhizosperic soils, and the organic solvent extractable residues were the main
form in far-rhizosperic soils. The three forms of sulfonamides showed relatively
lower toxicity to luminescent bacteria with the relative inhibition rates less
than 30%. The toxicity of water soluble residues was lower than that of the
organic solvent extractable residues, and the bound residues showed the lowest
toxicity to luminescent bacteria. The contents and relative inhibition rates of
water soluble residues in rhizosperic soils were higher than those in far
rhizosperic soils, while the contents and relative inhibition rates of organic
solvent extractable and bound residues in rhizosperic soils were lower than those
in far-rhizosperic soils.
PMID- 29965173
TI - [Alleviation Effects of Exogenous Melatonin on Ni Toxicity in Rice Seedings].
AB - The alleviation effect of exogenous melatonin (MT) on Ni toxicity in rice
seedings was investigated. The results showed that low concentration of Ni stress
(10, 50 MUmol.L-1) had little effect on the growth of root of rice seedings,
while higher concentration of Ni stress (100-1000 MUmol.L-1) significantly
inhibited the growth of rice root. Compared with the control treatment, the
addition of 100 and 1000 MUmol.L-1 Ni would decrease the total length and surface
area of root by 63.3%-98.0% and 56.9%-96.3%, respectively. The results showed
that addition of exogenous melatonin had a positive effect on the growth of rice
seedings under Ni stress. This kind of positive effect was even more obvious in
the root of rice seedings. The total length of rice root decreased by 58.4%-83.8%
at Ni concentration of 100 MUmol.L-1, whereas it decreased by only 8.7%-29.1%
when 100 MUmol.L-1 Ni and 10 MUmol.L-1 MT were added, compared with the control
treatment. The addition of exogenous melatonin had significant alleviation
effects on oxidative stress in rice seedings caused by Ni. Compared with the 100
MUmol.L-1Ni treatment, addition of 10 MUmol.L-1 exogenous MT could significantly
decrease the production rate of O2-. by 43.2%-50.2% and the relative electrolytic
leakage by 25.7%-31.6%, whereas increase the activities of CAT by 21.9%-33.7% and
the soluble protein content by 82.6%-84.6%. The results suggested that
application of exogenous melatonin could effectively alleviate the toxic effects
of Ni on rice seedings.
PMID- 29965175
TI - [Effect of Sediments on Bioaccumulation of Mercury in Fish Body in the Water
Level-Fluctuating Zone of the Three Gorges Reservoir Area].
AB - Mercury (Hg) in the aquatic environment is easy to accumulate in fish. In order
to study the effect of the sediments on Hg accumulation in fish in the water
level-fluctuation zone of the Three Gorges Reservoir, we conducted a 90-days
simulated flooding experiment by using the sediments with different
concentrations of Hg. Our study showed that the concentrations of the total
mercury (THg) and methyl mercury (MeHg) in the overlying water increased after
flooding, and the concentrations in the muscle of fish kept increasing in the
period of experiment, the concentrations in the viscera and head increased in the
earlier period but seemingly decreased in the later period. The bioaccumulated Hg
content in the fresh was higher than that in the viscera and head, between which
there was no significant difference. Compared with the control group (no
sediment), the presence of sediments obviously increased the content of Hg
bioaccumulated in fish, and the bioaccumulated Hg level increased with the Hg
concentrations in sediment. The THg and MeHg in different fish parts presented a
similar variation trend with the BCF ranging 1.93*105-8.89*105 for MeHg and
1.3*103-12.8*103 for inorganic mercury, indicating that MeHg was more prone to
accumulate in fish. The MeHg in fish was significantly related with THg, and
accumulated MeHg occupied about 80.1% (muscle), 79.3% (visceral) and 66.7% (head)
of increased THg. After the reflooding of the sediment in the water-level
fluctuating zone, net methylation could occur with MeHg as the product, and then
MeHg would diffuse to overlay water, further increasing the Hg bioaccumulation in
fish. Therefore, the potential pollution risk of Hg in the water-level
fluctuationg zone with large area of the Three Gorges Reservoir cannot be
ignored.
PMID- 29965176
TI - [Bioaccumulation and Correlation of Heavy Metals in Human Hairs From Urban and
Rural Areas of Chongqing].
AB - In the present study, human hair samples were collected in Chongqing to detect
the concentrations of heavy metals including Cd, Cu, Ni, Pb and Zn by flame
atomic absorption spectrophotometry. Meanwhile, the relationship between the
content of heavy metals and age, gender and smoking habits was also analyzed, and
the potential sources of the heavy metals in human hair were understood through
correlation analysis and principal component analysis. The results showed that
the mean concentrations of Cd, Cu, Ni, Pb and Zn were 3.1, 24.3, 9.7, 42.8 and
209.6 MUg.g-1, respectively in urban areas, while the mean contents were 0.9,
15.8, 5.6, 15.2 and 173.4 MUg.g-1, respectively in rural area. The residents
living in urban areas exhibited significantly higher concentrations than those in
rural area, revealing the same heavy metal pattern with that in soils (t-test,
P<0.01). No obvious trend was observed between the contents of heavy metals and
age, except that the contents of Cu and Zn were increasing with the growth of
age. Significantly higher concentrations of Cd and Pb were both observed in male
hair and smokers than those in female and non-smokers, respectively in urban and
rural areas (P<0.01). Similar correlation patterns among Cd, Cu, Ni and Pb were
found both in urban and rural areas. According to principal component analysis,
Cu, Ni and Pb contaminations had similar sources in urban areas, whereas Cd, Ni
and Pb had similar sources in rural area.
PMID- 29965178
TI - [Performance Improvement of Microbial Fuel Cell with Polyaniline Dopped Graphene
Anode].
AB - Microbial fuel cell (MFC) technology has potential in recovering bioelectricity
from different types of waste, which attracts more and more attention in the
field of environment and energy. However, low power density, high cost and low
substrate degradation rate, closely associated with anode performance, limit its
practical application. In this study, proportional polyaniline (PANI) together
with graphene was chosen to obtain the PANI dopped graphene composite. The as
received composite was modified onto the surface of glassy carbon electrode. The
results of electrochemical analysis showed that the optimal mass ratio of
graphene was 20% for cyclic voltammetry (CV) and linear sweep voltammetry (LSV)
analysis. The anodes with 5% graphene produced a peak power density of (831+/-45)
mW.m-2, which was 1.2, 1.3, 1.3, 1.5, 1.8 times of those with 20% graphene, 1%
graphene, graphene, PANI and carbon cloth, respectively. Moreover, 5% graphene
reactors showed the maximum values in output voltage, open-circuit voltage (OCV),
chemical oxygen demand (COD) removal rate, coulombic efficiency (CE), and biomass
density. The polarization resistance was only (24+/-2)Omega in 5% graphene
reactors,which was 19.8% of that of carbon cloth. The results of electrochemical
analysis were not consistent with those of bioelectrochemical analysis,
demonstrating that the biocompatibility of electrode was one of the important
factors affecting MFC performance. 5% graphene anode showed full advantages of
graphene and PANI, which improved the performance of MFC.
PMID- 29965177
TI - [Microbial Community Structure and Diversity in Cellar Water by 16S rRNA High
throughput Sequencing].
AB - This study was aimed to explore the bacterial diversity of cellar water as well
as to study the relationship between the bacterial diversity and environmental
factors. The MiSeq high-throughput sequencing was used to analyze and compare the
bacterial diversity and community composition of samples from different cellar
water samples. Overall 1605 optimized reads were obtained from four samples based
on high-throughput sequencing of the V4 region of the 16S rRNA gene. Bacterial
species detected in these samples covered 22 phyla,42 classes,71 orders,115
families, 146 genera. Analysis showed that the bacterial diversity was very high
in these samples, and there were differences among different samples. The
distribution characteristics of the dominant bacteria showed patterns of a large
number of rare species and a few common types. Taxonomic assignment analysis
indicated that Bacteroidetes,Proteobacteria,Actinobacteria,Verrucomicrobia,OD1
dominated in the Cellar water, and accounted for 87.1% to 94.8% at phylum level.
The predominant groups were Actinobacteria,Acidimicrobiia,Cytophagia,
Flavobacteriia, Sphingobacteriia,alpha-Proteobacteria,beta-Proteobacteria,gamma
Proteobacteria,Opitutae, Verrucomicrobiae,Pedosphaerae and ZB2 at class level. At
genus level
Rhodobacter,Dechloromonas,Flavobacterium,Acinetobacter,Comamonas,Pseudomonas,Hydr
genophaga,et al were the abundant taxa, which were mainly denitrifying bacteria
and heterotrophic nitrification-aerobic denitrification bacteria. The result of
RDA suggested that the influences of different environmental factors on different
microbes were different. Bacterial community II had significant positive
correlation with UV254,permanganate index,BOD5,and Bacterial community III had
significant positive correlation with TN,NO2--N,NO3--N,TP,NH4+-N. This research
should deepen the understanding on microbial community in Cellar water, and
provide references for the association of bacterial composition and diversity
with environmental factors.
PMID- 29965179
TI - [Brief Introduction of Pollution Sites Remediation and Risk Assessment and Its
Policy Making in United States].
AB - Site remediation has become an imperative part of environmental protection in
China due to recent economic development, urban spreading, new industries
replacing old ones, relocation of old industrial sites, and increased
environmental conscience. This paper mainly introduced the concept, method,
calculation, risk assessment and management for polluted sites remediation based
on experience from California, USA. Further, the paper presented the concept of
vapor intrusion and how to use vapor intrusion methodology to determine site
remediation standard. Mathematical modeling approaches were also discussed in
terms of how to determine the residual pollutant concentrations in soil and how
to calculate indoor vapor concentrations. Based on risk assessment, California
Environmental Protection Agency, Water Resources Control Board issued a 'Low
Threat Underground Storage Tank Case Closure Policy' for impacted underground
storage tank sites. The numerical criteria in the Policy were based on
calculations of human health risk assessment. Finally, a real case study in
California, USA, was presented to demonstrate how the risk assessment
calculations were applied in polluted site remediation, which helps to answer the
question of 'how clean is clean'.
PMID- 29965180
TI - [Correlation Analysis of the Urban Heat Island Effect and Its Impact Factors in
China].
AB - Urban heat islands (UHIs), which are urban areas with higher surface or air
temperatures than surrounding rural areas, can further enhance the heat stress
already exacerbated by global warming. This poses great challenges to human
health and sustainable development. China has been burdened with heavy air
pollution in recent years, and the effect of haze pollution on UHIs is still far
less well understood. This study investigated the spatial variations of daytime,
nighttime, and seasonal surface UHI effects in China during 2003-2013, based on
MODIS land surface temperature data, and analyzed the correlations between the
UHI effect and its impact factors from both biophysical and biochemical
perspectives. Our results show that MODIS-derived annual nighttime UHI effect
(3.4 K+/-0.2 K, mean+/-1 s.e.) is higher than the annual mean daytime UHI effect
(2.1 K+/-0.3 K). The daytime UHI effect is strongest in summer and weakest in
winter but contrasts with the seasonal variation characteristics of nighttime UHI
effect. During daytime, UHI effects in humid and semi-humid regions are much more
obvious than those in semi-arid/arid regions; during nighttime, the UHI effect in
semi-humid and semi-arid/arid regions is much stronger than that in humid
regions. A Daytime Urban Cool Island effect exists in semi-arid/arid regions
during spring, autumn, and winter seasons. Population, vegetation activity, and
irrigation are three factors controlling annual mean daytime UHI effect. The
nighttime UHI is significantly influenced by latitude, albedo, precipitation, and
aerosol concentrations. We provide evidence for a long-held hypothesis that the
biogeochemical effect of urban aerosols is an important contributor to the UHI
effect. The important role played by rural background environment in calculating
the UHI effect is further discussed in terms of surface aerodynamic roughness and
the contrast in albedo between urban and rural areas. Mitigation of haze
pollution has a co-benefit of reducing the UHI effect and heat stress for urban
dwellers. It is also conducive to reducing negative impacts of regional and
global climate change.
PMID- 29965181
TI - [Application of Satellite Remote Sensing in NOx Emission Control].
AB - Tropospheric NO2 vertical column densities (VCDs) from ozone monitoring
instrument(OMI) were analyzed to evaluate the decrease in NOx emissions during
two special events, 70th anniversary of the end of World War II in 2015 and the
G20 summit in 2016. Results showed a positive correlation between NO2 VCDs and
near ground NOx emissions and verified that the NOx emission control policy
during "12th five-year plan" were remarkably effective, with a 24.98% drop in
VCDs in five years. At the early stage of "13th five-year plan", in 2016, NO2
VCDs decreased by 3.18% year-on-year, showing a consistent drop in NOx.
PMID- 29965182
TI - [Control Models and Effect Evaluation of Air Pollution in Jing-Jin-Ji Urban
Agglomeration].
AB - Controlling air pollution in the Jing-jin-ji urban agglomeration (JJJUA), the
most seriously polluted area in China, is related to the integrated development
strategy for the region. Based on the national and regional implementation of air
pollution control measures in recent years, the hierarchical cross-regional multi
directional linkage (HCML) air pollution prevention and control model was applied
in this study. The effect of air pollution control was evaluated by monitoring
the pollutants, SO2, NO2, PM10, PM2.5, O3, and CO, at 112 monitoring sites in 13
cities in 2014-2015. The results can be summarized as follows:1 The HCML model is
an interrelated framework at the horizontal and vertical level. Under the efforts
provided by the central, urban agglomeration, and city governments, this multi
level governance model serves as an effective tool to resolve the issues related
to air pollution beyond the borders of municipalities. Environmental regulations
on certain industries, energy consumption structure, car ownership and usage, and
air quality supervision and warning systems are well established under this
governance model. 2 The air quality of the JJJUA has improved significantly in
the past two years. The concentrations of air pollutants significantly decreased,
with the exception of O3, and high pollution ranges significantly reduced from
north to south. The annual average concentrations of PM2.5, PM10, SO2, NO2, and
CO decreased by 17.84%, 14.61%, 37.55%, 4.82%, and 16.18%, respectively. The
number of days meeting the air quality standards increased for all pollutants
except NO2. Based on the current situation and unsolved problems of air
pollution, the JJJUA area needs certain measures including diversifying the
governance subjects, joint legislation (beyond municipalities) on air pollution
to regulate pollution discharge, enhancing public awareness on air pollution and
its health impacts, carefully examining sources of air pollution in winter to
reduce pollution, and to better understand the sources of ozone and adopt
effective control measures.
PMID- 29965183
TI - [Pollution Characteristics of Aerosol Number Concentration in Winter and Spring
in a Northern Suburb of Nanjing].
AB - Using APS-3321, the atmospheric aerosol number concentrations (0.5-20 MUm) were
continuously monitored to analyze the characteristics of winter and spring
pollution in 2014 in a northern suburb of Nanjing. The average number
concentrations were (364.8+/-297.8) cm-3 and (79.6+/-62.4) cm-3 in winter and
spring, respectively; fine particles (0.5-1.0 MUm) accounted for 87.8% and 86.6%
of the total, respectively. There were significant variations in number
concentration at different periods. The diurnal variations in number
concentrations were evident with high concentrations at night and low
concentrations during the day. The early peaks were at 07:00 and 09:00, and
number concentrations began to increase rapidly starting at 17:00 and 18:00 in
winter and spring, respectively. The distribution of the number concentrations
was unimodal, with peak sizes between 0.583 and 0.626 MUm in winter and less than
0.542 MUm in spring. With the increase in relative humidity, aerosol number
concentrations increased gradually; at the same time, the peak size moved to a
larger diameter which reflected the influence of hygroscopic growth of aerosols.
During the total observation period, it reached 83.3% of the proportion of hazy
days. The number concentration of particles less than 2.0 MUm increased
significantly with the increase in the haze pollution level, which was more
obvious in winter. In spring, the proportion of fine particles increased with the
increase in the haze level but in winter, it decreased during hazy days due to a
significant increase in particle size caused by aging. The analysis of the
typical pollution process in January indicated that there was a strong
correlation between the source of air mass and the surface wind direction.
Pollutants transmitted from the northern Jiangsu Province and the accumulation of
pollutants due to slow winds were important causations of the pollution process.
PMID- 29965184
TI - [Source Apportionment and Size Distribution of Aerosols at Lin'an Atmosphere
Regional Background Station During Winter].
AB - Using a wide-range particle spectrometer (WPS), an environmental management
system (EMS), KC-120H middle volume sampler, a 850 professional ion
chromatography analyzer, and heat/light carbon analyzer (DRI2001A), we observed
the number concentration of aerosols with sizes ranging from 10 nm to 10 MUm, gas
concentrations, and concentrations of PM2.5, water-soluble ions, OC, and EC in a
Lin'an atmospheric background station from January 9 to 31, 2015. The positive
matrix factorization (PMF) model was applied for source apportionment, and the
size distribution and diurnal variations of emission sources were analyzed based
on the meteorological data. The average aerosol concentration was 5062 cm-3.nm-1
and PM2.5 mass concentration was 123.6 MUg.m-3. The average concentrations of NO3
, SO42-, and NH4+, the main water-soluble ions in PM2.5 were 19.2, 15.4, and 10.8
MUg.m-3, which accounted for 37.9%, 30.4%, and 21.4% of total water-soluble ions,
respectively. Theaverage concentrations of OC and EC were 24.4 MUg.m-3 and 6.6
MUg.m-3. Secondary aerosol formation, coal combustion, motor vehicle emissions,
dust, andbiomass burning were the main sources of PM2.5 in Lin'an during winter
with contributions of 42.3%, 21.4%, 17.1%, 8.7%, and 10.6%, respectively.
Different sources had different aerosol number concentration distributions. The
aerosol number concentration spectra of secondary sources, vehicle emissions,
dust, and biomass burning followed unimodal-type distributions with peaks at 120,
50, 100, and 90 nm. Coal particle number concentration was a bimodal distribution
which exhibited peak values at 25 nm and 100 nm (19842 cm-3.nm-1 and 18372 cm
3.nm-1, respectively). The spectra of surface concentrations of secondary
sources, coal combustion, motor vehicle emissions, dust, and biomass burning
followed a three-peak distribution. The peaks were at 650, 210, 160, 180, and 575
nm. The diurnal variations of particle number concentrations influenced by
diurnal variations in the boundary layer and human activities were consistent
with the variations in surface concentrations, which displayed bimodal-type
distribution.
PMID- 29965185
TI - [Seasonal Variations in Particle Size Distribution and Water-soluble Ion
Composition of Atmospheric Particles in Chengdu].
AB - Size-resolved atmospheric particles were collected monthly from February 2012 to
January 2013 on the campus of Chengdu University of Technology using the Anderson
multi-stage impactor sampler. The mass concentrations of these samples and the
contents of nine water-soluble ion species were analyzed. The results showed that
the annual average concentrations of PM2.1 and PM11 in Chengdu during the
sampling period were (125.9+/-56.14) MUg.m-3 and (224.5+/-83.64) MUg.m-3,
respectively. The highest mass concentration of particulate matter was observed
in winter, followed by spring while the lowest was in autumn. The average content
of water-soluble ions in particulate matter in Chengdu was about 37.15 MUg.m-3
and the order of water-soluble ion mass concentrations was SO42- > NO3- > NH4+ >
Ca2+ > Cl- > Mg2+ > K+ > Na+ > F-. Meanwhile, SO42-, NO3-, and NH4+ were the
major water-soluble ionic components that accounted for 78% of total water
soluble ions. Unimodal distribution was observed for SO42-, NO3-, and NH4+ mainly
in fine particles, while Ca2+ and F- were concentrated in coarse particles and
their distribution was also unimodal. Similar size distributions were found for
Cl- and K+, as well as Mg2+ and Na+, both of which were bimodal. The content of
water-soluble ions in both fine and coarse particles during winter and spring was
significantly higher than that in summer and autumn in Chengdu. Based on the
correlation analysis for major ions, SO42-, NO3-, and NH4+ in fine particles are
likely in the form of (NH4)2SO4, NH4HSO4, and NH4NO3. In coarse particles, the
major water-soluble ions (i.e. SO42-, NO3-, and Ca2+) might exist in the forms of
Ca(NO3)2 and CaSO4. The secondary formation processes, soil dust, and biomass
burning are the major sources of water-soluble ion species in the particulate
matter in Chengdu.
PMID- 29965187
TI - [Chemical Characteristics and Sources of Heavy Metals in Fine Particles in
Beijing in 2011-2012].
AB - In order to investigate the chemical characteristics and sources of atmospheric
heavy metals, PM2.5 samples were collected every three days during the summer of
2011 and summer of 2012. The samples were analyzed for Li, V, Cr, Mn, Co, Cu, Zn,
As, Se, Ti, Ga, Ni, Sr, Cd, In, Ba, Tl, Pb, Bi, and U by ICP-MS, with an emphasis
on seven major heavy metal elements (Zn, Pb, Mn, Cu, As, V, and Cr). The
concentrations of Zn, Pb, Mn, Cu, As, V, and Cr were (331.30+/-254.52), (212.64+/
182.06), (85.96+/-47.00), (45.19+/-27.74), (17.13+/-19.02), (4.92+/-3.38), and
(9.04+/-7.84) ng.m-3 in PM2.5 in Beijing during the summer of 2011 and the summer
of 2012. In the autumn and winter seasons, PM2.5/heavy metal pollution is more
severe than in spring and summer, which may be related to the increase in coal
combustion used for heating in autumn and winter in Beijing. Haze pollution
enhances the concentrations of seven heavy metals in PM2.5 in Beijing and the
enhancement shows seasonal variations. The source analysis suggested that dust
(including building dust and road dust) and coal combustion might be two most
important sources of heavy metals in Beijing, and transport and other industrial
sources cannot be ignored.
PMID- 29965186
TI - [Seasonal Variation and Source Apportionment of Water-Soluble Ions in PM2.5 in
Quanzhou City].
AB - In this study, the seasonal characteristics of water-soluble ions (WSIs) present
in fine particulate matter (PM2.5) in Quanzhou City were investigated. PM2.5
samples were collected at five different sites in the city from March 2014 to
January 2015 and the concentrations of Na+, NH4+, K+, Ca2+, Mg2+, F-, Cl-, NO3-,
and SO42- were determined by ion-exchange chromatography. In order to identify
the sources of these WSIs, the positive matrix factorization (PMF) analysis was
applied. The seasonal variations in total WSI concentrations were found to
decrease in the order of spring > winter > summer > autumn. The ions SO42-, NO3-,
and NH4+ were the major WSIs found in PM2.5, accounting for 90.3%+/-3.3%, 68.8%+/
11.7%, 78.9%+/-7.1%, and 74.0%+/-18.4% of the total amount of ions found in
spring, summer, autumn, and winter, respectively. These results suggested that
the level of secondary ions was relatively high in the spring season. The anion
to-cation ratio in each of the four seasons was less than one, which indicated
that PM2.5 in Quanzhou City was slightly alkaline. Furthermore, NH4+ ions in
PM2.5 mostly existed in the form of (NH4)2SO4, NH4HSO4, and NH4NO3 during spring
and winter, while they were primarily found as NH4HSO4 and NH4NO3 in the summer
and autumn seasons. PMF analysis revealed that marine salt, secondary sources,
fugitive dust from construction, municipal incineration, and biomass burning were
the main potential sources of the ionic components of PM2.5.
PMID- 29965188
TI - [Pollution Assessment and Source Analysis of Metals in PM2.5 in Haicang District,
Xiamen City, China].
AB - To determine the spatial-temporal distributions and potential sources of metals
in PM2.5 and assess health risks from heavy metals, 348 PM2.5 samples were
collected in the Haicang District of Xiamen, China from April 2015 to January
2016. Metals (K, Ca, Na, Mg, Al, Zn, Cu, Fe, Ti, As, V, Mn, Ba, Co) in PM2.5 were
detected using an X-ray fluorescence analyzer (XRF). Pollution assessment was
performed via enrichment factor calculation and health risk assessment. Potential
sources were explored using Pearson's correlation coefficient, principal
component analysis, and the HYSPLIT Trajectory Model. Results showed that the
total concentration of 14 metal elements contributed to 5.4%-10.6% of PM2.5
during the sampling period. The total concentration of metals was higher in
spring and winter than those in summer and autumn. The concentrations were higher
in the port and the industrial areas than in residential areas and background
locations, in agreement with the seasonal and spatial distribution of PM2.5. The
frequency of PM2.5 daily concentrations exceeding the Chinese Ambient Air Quality
Standards was higher in the port and residential areas in the summer due to
operations at the port and the wind direction. Zn concentration was the highest
in the industrial area followed by the background location. Meanwhile, the
highest concentration of V was observed in the port area; V concentration in the
residential area was high in the summer. These variations in Zn and V indicated
that the elements emitted in the polluted areas migrated easily to residential
and background areas. K concentrations were the highest in winter and As showed a
higher rate of exceeding the standard in winter and spring, indicating that
activities, such as biomass burning and coal combustion in the winter severely
impacted air quality. The enrichment factors of Cu, Zn, As, Co, Na, and Mn varied
considerably, from 67 to 8,449. The total risk level for non-carcinogenic heavy
metals (Zn, Cu, Mn) was lower than the average level of risk acceptance (1*10-6 a
1) and Mn contributed 74%-88% of the total risk level of Zn, Cu, and Mn. The
combined results of the correlation analysis and the principal component analysis
revealed that metals in PM2.5 were mainly came from re-suspension of ground dust,
motor vehicle emissions, coal combustion, industrial emissions, and heavy oil
combustion, with contributions of 34.5%, 12.5%, 10.6%, and 7.8% respectively. The
HYSPLIT Trajectory Model showed that Xiamen was affected by the local air mass in
spring, autumn, and winter, but not in summer. Moreover, the rise of PM2.5 in
spring and winter was attributed to air masses traveling through the Yangtze
River Delta.
PMID- 29965189
TI - [Characteristics and Health Risk Assessment of Metallic Elements in PM2.5
Fraction of Road Dust].
AB - In order to analyze and compare the pollution characteristics and risks to human
health of metallic elements in the PM2.5 fraction of urban road dust (RD) and
park road dust (PRD), particles smaller than 2.5 MUm were suspended to filters by
a re-suspension system and concentrations of Na, Mg, Al, Fe, Cu, Mn, Ni, Sb, Zn,
Cd, and Pb were quantified. Results showed that the average concentrations of Cu
and Sb in RD were 626 mg.kg-1 and 23 mg.kg-1, significantly higher than that in
PRD (274 mg.kg-1 and 11 mg.kg-1). This indicated that the elemental composition
of RD was influenced by non-exhaust emissions. The geoaccumulation Index (Igeo)
of each detected element showed that samples were strongly to extremely
contaminated by Cd (4 < Igeo < 5), moderately to strongly contaminated by Cu, Sb,
Zn, and Pb (2 < Igeo < 4), and uncontaminated to moderately contaminated by Ni
and Mn (Igeo < 1). The hazard index (HI) values of Sb, Pb, Cu, Ni, Zn, and Cd
were less than 1 and the incremental lifetime cancer risk (ILCR) values of Ni and
Cd were less than 10-6, indicating that these elements of RD and PRD are not
associated with any cancer risks or non-cancer health risks.
PMID- 29965190
TI - [Seasonal Variations in PM10 and Associated Chemical Species in Jiuxian Mountain
in Fujian Province].
AB - PM10 samples were collected at the top of Jiuxian Mountain in Fujian Province
from March 2011 to January 2012 and were analyzed for inorganic water-soluble
ions and dicarboxylic acids to investigate their seasonal variations and sources.
The results showed that PM10 and its associated species exhibited much higher
levels in the spring than those in other seasons but the total contribution of
the nine species of dicarboxylic acids to PM10 (0.51%+/-0.41%) was significantly
lower than that of the water-soluble ions (18.07%+/-8.73%). The water-soluble
ions were characterized by the highest concentrations of SO42- and NO3-, followed
by Na+ and NH4+. Significant positive correlations were observed between cation
and anion equivalents, as well as between NH4+ and SO42- or NO3- equivalents.
Individual dicarboxylic acid showed a monotonically decreasing trend with
increasing carbon number in which oxalic acid accounted for approximately 75% of
the total dicarboxylic acids. Characteristic ratios of malonic acid to succinic
acid and adipic acid to azelaic acid, MODIS fire spots, and backward trajectories
showed that dicarboxylic acids mainly originated from secondary reactions in the
atmosphere and that the direct contributions of open biomass burning to
dicarboxylic acid concentrations were negligible.
PMID- 29965192
TI - [Analysis of Atmospheric Particulate Matter Pollution Characteristics by LIDAR in
Beijing During Spring Festival, 2016].
AB - Real-time aerosol extinction retrieved by Micro-pulse LIDAR and concentrations of
PM2.5 and PM10 in Beijing were analyzed to investigate the air quality during the
Spring Festival. The results showed that fireworks on the New Year's Eve resulted
in a sharp increase in particulate matter concentrations in a short time. The
maximum concentration of PM2.5 at Guanyuan station was 639.3 MUg.m-3, which
increased by nearly 30 times in 9 h. The maximum hourly concentration of
particulate matter at Dingling and Liulihe suburban stations were significantly
higher than that in Guanyuan station, the maximum values were more than 1000
MUg.m-3. The particulate matter levels were continuously high on February 10-12
and the concentration of particulate matter at Dingling and Liulihe suburban
stations were higher than that at Guanyuan. LIDAR results showed no obvious
changes in the extinction coefficient at Dingling on the New Year's Eve. The
extinction coefficient at Liulihe was greater than 1 km-1, but the particulate
matter pollution was concentrated at altitudes less than 400 m. The extinction
coefficient at Chegongzhuang was still higher than 0.4 km-1 at 500 m; however,
the duration of pollution was shorter than that of Liulihe. The extinction
coefficients at 105 m at all three stations during the New Year's Eve were
significantly higher than those at 405 m. There were significant differences in
the vertical extinction characteristics of the three sites. The background
maximum values of Dingling, Chegongzhuang, and Liulihe were 0.09 km-1, 0.20 km-1,
and 0.19 km-1 under 1.0 km, respectively. The maximum extinction coefficients at
00:00 (midnight) were 0.23 km-1, 1.36 km-1, and 1.19 km-1, which were 2.6 times,
6.8 times, and 6.0 times higher than the background value at the same time,
respectively. In summary, discharge of fireworks led to a dramatic increase in
the extinction coefficient of particulate matter. Temperature inversion and lower
wind speeds were the main meteorological factors that contributed to this
pollution event.
PMID- 29965191
TI - [Characteristics of C2-C6 Hydrocarbons During the Winter Air Pollution Period in
Beijing Urban Area].
AB - A C2-C6 hydrocarbons monitoring campaign was carried out in the Beijing
Southeastern Urban Area during December 2015. Twenty-five compounds excluding
benzene were detected by an on-line VOCs analyzer; the sum of their
concentrations is referred to as C2-C6 HCs in this study. During the monitoring
period, C2-C6 HCs ranged from 12.4*10-9 to 297.5*10-9. The mean value of C2-C6
HCs reached 29.4*10-9, 63.2*10-9, 85.5*10-9, 94.9*10-9, and 131.8*10-9,
respectively, in AQ I (air quality) (hourly PM2.5<35 MUg.m-3), AQ II (hourly
PM2.5:35-75 MUg.m-3), AQ III (hourly PM2.5:75-150 MUg.m-3), AQ IV (hourly
PM2.5:150-250 MUg.m-3), and AQ V (hourly PM2.5:>250 MUg.m-3). Moreover, the mole
percentage of alkanes, alkenes, and ethyne significantly varied, 47% vs. 59%, 45%
vs. 30%, and 7% vs. 12% (AQ I vs. AQ V). The diurnal variation of C2-C6 HCs
presented two peaks at 08:00-09:00 and 17:00-18:00 not only in clean days (when
24-h PM2.5<75 MUg.m-3) but also in polluted days (when 24-h PM2.5>75 MUg.m-3).
This result is consistent with the normal traffic pattern and indicates the
significant impact of vehicle emissions on atmospheric hydrocarbon
concentrations. Furthermore, we calculated the HCs/CO (*10-9/*10-6) ratio to
prevent the impact of meteorological diffusion on C2-C6 HCs and to trace the
physical transport process and the chemical degradation process of hydrocarbons.
The C2-C6 HCs/CO ratio and the individual hydrocarbon to CO ratio presented a
notable decreasing trend with worsening air quality, 90.6 (AQ I), 63.8 (AQ II),
56.9 (AQ III), 37.4 (AQ IV), and 36.4 (AQ V). However, the rate of decrease in
the ratio of individual hydrocarbons to CO in the polluted period (AQ III-V)
relative to the clean period (AQ I-II) was never effectively related to the
kinetic parameters of the reactions with the OH radical. Therefore, the strong
chemical degradation of C2-C6 hydrocarbons in the polluted air was denied as the
main reason. The HYSPLIT trajectory model showed that the transported air mass
from the north and northwest and from the south and southwest prevail in the
clean period and in the polluted period, respectively. Compared to the northern
region, there were more sources of fossil fuel combustion in the southern region,
which led to a lower HCs/CO ratio for the air mass in the southern region.
Therefore, the increase in C2-C6 hydrocarbons during the polluted period was not
only caused by the accumulation of local emissions but also by the air mass
transport from the south.
PMID- 29965193
TI - [Influence Factors and Sensitivity of Ozone Formation in Langfang in the Summer].
AB - The diurnal variations in ozone concentrations in the summer were studied using
the temperature, wind speed and direction, total cloud cover, and solar radiation
intensity data collected in Langfang, China. The ratio of volatile organic
compounds to nitrogen oxides (VOCs/NOx) and the EKMA curve were studied to
analyze the sensitivity of ozone formation. The results showed that:1 The ozone
generation rate and ozone concentrations were positively correlated with the
solar radiation intensity with Pearson correlation coefficients of 0.61 and 0.48,
respectively. Both the ozone generation rate and the solar radiation intensity
reached their peak at about 12:00, while the ozone concentration reached its peak
at about 16:00, which lagged behind the peak of the solar radiation intensity by
4 h. 2 The correlation coefficient between the ozone generation rate and the
temperature was 0.44, between the ozone concentration and temperature was 0.68.
The ozone generation rate and ozone concentrations were inversely correlated with
total cloud cover with correlation coefficients of -0.24 and -0.45, respectively.
3 The ozone concentrations in Langfang were high when the winds were from the
west, south, or southeast. 4 The ozone concentrations in Langfang were more
sensitive to VOCs than to NOx; thus, they can be reduced efficiently by
controlling the VOCs emissions.
PMID- 29965195
TI - [Distinguishing the Properties and Sources of the Dissolved Organic Matter in
Karst Reservoir Water During Winter Using Three-Dimensional Fluorescence Spectrum
Technology:A Case Study in Wulixia Reservoir of Guangxi Province].
AB - In recent years, the fluorescence spectrum technology has been widely applied to
study the physical and chemical properties of dissolved organic matter (DOM) in
natural water. In order to reveal the properties of the dissolved organic matter
in reservoir water, the three-dimensional fluorescence spectrum and the parallel
factor analysis were used to determine the properties of DOM and its sources in
the Wulixia reservoir during the winter of 2016. Moreover, the chemical
characteristics of water and the relative proportion of DOM fluorescent
components were estimated. Results show that:1 Ca2+ and HCO3- are the main
cations and anions in the Wulixia reservoir during winter. The water is mainly
controlled by the carbonate balance system and dissolved organic carbon (DOC)
accounted for about 91% of total organic carbon (TOC). 3 DOM from the Wulixia
reservoir can be divided into three components:fulvic acid, humic acid, and
tryptophan. 3 The parameters, fluorescence index, humification index, biological
index, and freshness index show the existence of DOM in the Wulixia reservoir.
Microorganisms have a significant effect on DOM composition.
PMID- 29965194
TI - [Impact of Human Activities on Water-Rock Interactions in Surface Water of
Lijiang River].
AB - The influence of human activities on karst surface water quality has received
increasing attention. To explore the impact of human activities on water-rock
interactions in karst surface water, water samples were collected from July to
November in 2016 in the Lijiang River, which is dominated by human activities.
The samples were analyzed for the hydrochemistryand the characteristics of
delta13CDIC. The results show that:1The Lijiang River is mainly characterized by
HCO3-Ca chemical composition.. The SO42- and NO3- concentrations are inferior to
HCO3- concentrations in the anion composition; besides, the concentrations of
SO42- and NO3- in the river between Guilin and Yangshuo are higher than in the
other sampling sites, caused by tourism and urban development. 2Equivalent ratios
of[Ca2++Mg2+]/[HCO3-] are between 1.01 and 1.51 and the equivalent ratios
of[Ca2++Mg2+]/[SO42-+NO3-+HCO3-] are between 0.85 and 1.12, indicating that the
sulfuric acid and nitric acid have participated in the water-rock interaction.
3The proportions of carbonic acid dissolving carbonate rocks range from 32.10%
98.01% with an average of 75.89%. The proportions of sulfuric acid and nitric
acid dissolving carbonate rocks vary from 1.99%-67.90% with an average of 24.11%.
The proportions of sulfuric acid and nitric acid dissolving carbonate rocks in
the rainy period with an average of 24.31% is higher than in the brief rain
period with an average of 23.88%. In addition, the proportions of sulfuric acid
and nitric acid dissolving carbonate rocks present a fluctuated increasing trend
from upstream to downstream and the maximum strength and the minimum strength of
the sulfuric and nitric acid dissolving carbonate rocks occur in Lingchuan and
Huajiang, respectively. 4 HCO3- mainly originated from the carbonate rocks
dissolved by carbonic acid, with an average of 83.58%, followed by the carbonate
rocks dissolved by sulfuric acid and nitric acid, with an average of 14.24%. The
contribution of carbonic acid weathering silicate rocks is the smallest with an
average of 2.18%. 5 delta13CDIC of the Lijiang River ranges from -11.950/00-
7.610/00; the calculated delta13CDIC-rock using the mixture endmember model
ranges from -14.240/00--7.230/00. delta13CDIC is close to delta13CDIC-rock in the
rainy period and delta13CDIC is significantly higher than delta13CDIC-rock in the
brief rain period. The difference between delta13CDIC and delta13CDIC-rock is
caused by the influence of aquatic photosynthetic organisms.
PMID- 29965196
TI - [Analysis of Temporal and Spatial Variations in Trace Element Migration in Karst
Critical Zone:An Example of Jiguan Cave, Henan].
AB - To explore the temporal and spatial variations and the process of trace element
migration in the karst critical zone, continuous fixed-point monitoring and
sampling analysis was applied to measure each cave system component, which
includes rainfall, soils, bedrock, drip waters, and their aerial sediment.
Approximately 650 experimental data were obtained from October 2009 to May 2015
in a typical karst critical zone in north China-an interactive zone of the Jiguan
Cave in the west Henan Province. The variations in and the migration rules of Ca,
Mg, Ba, Sr, and delta13C as well as their ratios to different components were
studied. The results show that:1 Soil and bedrock are the main sources of drip
water. The values of Mg, Ba, and Sr are consistent with the "soil-bedrock" two
end-members model and their respective proportions are 43.6:56.4, 1.01:98.09, and
47.2:52.8. 2 From the spatial perspective, element migration of each component in
the cave system interactive zone is interrelated. Drip water inherits the signals
of the soil and bedrock and the modern sediment can continue the element
information of the drip water. Elements in the soil profile cause the leaching
and deposition effect and the subsoil better inherits the information of trace
elements in the bedrock. 3 From the temporal perspective, the migration of
elements in the cave system interactive zone is complex. Because of the leaching
effect, soil and drip water show obvious seasonal discrepancies. However, under
the influence of karst water migration path, the prior calcite precipitation
(PCP), and extreme arid and annual precipitation type, the seasonal discrepancy
in the element concentrations in drip water is smaller than in soil. The PCP
effect, selective leaching, and other factors change the continuity of elements
released from sediment to drip water. 4 In order to systematically and
comprehensively ascertain the trace element migration in the karst critical zone
and energy transformation rules, the study of cave system should be based on the
research of the cave's critical zone and should consider comprehensive
information ranging from the atmospheric origins to secondary sediments.
PMID- 29965197
TI - [Eutrophication and Characteristics of Cyanobacteria Bloom in the Summer in
Guishi Reservoir].
AB - Large-scale cyanobacteria bloom occurred in the summer of 2014 in the Guishi
Reservoir that is an important drinking water source for Hezhou City. The dynamic
change regularity, external pollution sources, and the phytoplankton community
characteristics during the bloom were investigated to evaluate the eutrophication
in the reservoir and to present effective prevention and control measures. The
results showed that nitrogen and phosphorus concentrations increased year by
year; water quality on some sites has been out of class II of national water
quality standards; and the main pollution source was the agricultural non-point
sources. Phytoplankton cell density was in the range of 8.60*106-5.36*108 cells.L
1 and chlorophyll a concentrations reached 74.48 MUg.L-1 during the bloom. The
dominant species was Microcystis wesenbergii whose density reached 5.36*108
cells.L-1. The cell density decreased over time and concentrated on the surface
and at the depth of 2 m underwater. The total phytoplankton cell density was
strongly correlated to total phosphorus, total nitrogen, nitrate nitrogen, and
the permanganate index, and was inversely correlated to transparency. The water
in the Guishi Reservoir was not polluted by microcystic toxins. Moreover, Guishi
Reservoir is in a meso-eutrophic state; therefore, the prevention and control of
the cyanobacteria bloom should focus on weather conditions and on reducing the
input of nitrogen and phosphorus to keep the nutrient levels low.
PMID- 29965198
TI - [Spatial and Temporal Distribution of Chlorophyll a and Its Relationship to Algae
and Environmental Factors in Aha Reservoir].
AB - As one of the drinking water sources for Guiyang City in southwest China, the Aha
Reservoir has an area of 190 km2 and a volume of 5.42*108 m3. The water depth is
less than 30 m, with an average depth of 13 m. Regulated by subtropical humid
monsoon climate, it has cool summers and warm winters, with an annual mean air
temperature of about 15.3C and an annual normal rainfall of approximately 1,129
mm. Impacted heavily by human activity (e.g., untreated industrial and domestic
sewage and agricultural non-point pollution sources), the eutrophication problem
in the Aha Reservoir has become more serious each year. In order to explore the
spatial and temporal distribution characteristics of chlorophyll a (Chl-a) and
its relationship to algae and the driving factors in the Aha Reservoir,
phytoplankton and water samples were collected in the dry period, normal period,
and flood period. The results showed a significant seasonal variation in Chl-a,
same as biomass, but not the same as the algal abundance. Highest Chl-a
concentration (91 MUg.L-1) occurred in the mean season with the dinoflagellate
bloom but during dry and wet seasons, they were only 8 MUg.L-1 and 16 MUg.L-1,
respectively. During the dry and flood periods, the Chl-a concentrations in
surface waters were slightly higher than the other layers caused by sufficient
light and dissolved oxygen. But in the normal period, the Chl-a concentrations in
surface waters were far higher than the other layers because of the
dinoflagellate bloom assembling in surface waters. Located at the reservoir
entrance of Jinzhong River, Dam sampling point owned higher Chl-a concentration
than Kuzhong as a result of higher nutrients. Correlation analysis indicated that
Dinoflagellate was positively correlated with Chl-a (R=0.798, P<0.01). Chl-a was
positively associated with total phosphorus, dissolved oxygen, pH value, and
total nitrogen (R=0.762, P<0.01; R=0.792, P<0.01; R=0.658, P<0.01; R=0.388,
P<0.05) and it had a negative correlation with the N/P ratio and nitrate nitrogen
(R=-0.37, P<0.05; R=-0.435, P<0.05). Stepwise regression analysis showed that TP,
N/P ratio, and DO were the most important factors influencing the temporal and
spatial distribution of Chl-a. Thermal stratification and water temperature were
also the significant factors that could not be ignored.
PMID- 29965199
TI - [Spatio-temporal Variations in Phytoplankton Community in Shahe Reservoir,
Tianmuhu, China].
AB - Monthly investigations of the phytoplankton community and the associated
environmental drivers during the past eight years in the Shahe Reservoir, Jiangsu
Province, China revealed the spatial and temporal variations of phytoplankton and
the associated driving factors in the reservoir. The results show that the
concentrations of total nitrogen (TN), total phosphorous (TP), turbidity (Turb),
suspended solids (SS), and chlorophyll-a (CHL) were the highest in the upstream
tributaries and the lowest in the downstream-linked reservoir. In contrast, the
highest Secchi disk depth (SDD) was recorded in the Shahe Reservoir and that the
lowest in the upstream tributaries. Significant differences in water quality
indices were recorded among the upstream tributaries, the transition region, and
the downstream-linked reservoir area (ANOVA, P<0.05). The biomass of
phytoplankton was the highest in the upstream tributaries and the lowest in the
reservoir. The highest biomass of phytoplankton was recorded in the summer and
the lowest in the winter. Synedra, Cyclotella, Cryptomonas, and Achnanthes were
the dominant genera in the spring; Synedra, Cryptomonas, Raphidiopsis, and
Phormidium were dominant in the summer; Cryptomonas, Synedra, Raphidiopsis, and
Aphanizomenon were dominant in the autumn; and Cryptomonas, Synedra, Achnanthes,
and Cyclotella were dominant in the winter. Synedra and Cryptomonas were the
dominant genera throughout the year. The correlation analysis shows that TP,
water temperature, and SDD were the most important driving factors for the
spatial and temporal variations of phytoplankton. Notable spatial differences
were recorded for Cryptomonas, while minimal variations were recorded for the
remaining species. A smaller number sampling sites and a higher sampling
frequency are needed to characterize the phytoplankton community in the Shahe
Reservoir.
PMID- 29965200
TI - [Spatio-temporal Variations, Contamination and Potential Ecological Risk of Heavy
Metals in the Sediments of Chenghai Lake].
AB - Heavy metals pollution in the sediments is one of the main factors impacting the
water quality and ecosystem health. In this study, concentrations of ten metals
in nine sediment cores from the Chenghai Lake were determined. Chronology of a
typical core (CH2012) was constructed by the 210Pb and 137Cs dating method. The
spatio-temporal variations in concentrations and contamination characteristics of
As, Cd, Cu, Hg, Ni, Pb, and Zn were evaluated. The potential eco-risks of heavy
metals in the surface sediments were studied by combining the ecological risk
index and sediment quality guidelines (SQGs) assessment as well as their
pollution levels (enrichment factors, EF). The metal concentrations in each
sediment core showed little vertical change with coefficients of variation of
less than 0.20, except for Cd, whose coefficient of variation was 0.59.
Spatially, the average concentrations of each metal showed minor difference among
the cores, with ratios ranging from 1.2 to 1.8, suggesting similar sedimentary
characteristics of metals in the whole lake. Cd and Pb were influenced by
anthropogenic contamination that has started in the mid-1980s. The pollution
level of Cd decreased in the past decade and still belongs to the moderate
pollution degree, whereas the pollution level of Pb increased continually and
could be classified as the weak pollution degree. The Hg contamination began in
the late 1990s, with EFs ranging from 0.9 to 1.6, belonging to the weak pollution
degree. The As, Cu, and Zn pollution occurred mainly near the surface sediments
with weak pollution degrees. Spatially, there were no obvious trends in pollution
levels of the metals. The heavy metals pollution is mainly influenced by
atmospheric deposition that originates from non-ferrous metal smelting emissions,
as well as agricultural and domestic discharges. As, Cu, Ni, Pb, and Zn in the
surface sediments have low potential ecological risks, whereas Hg and Cd may pose
middle-high potential risks.
PMID- 29965201
TI - [Characteristics of Phosphorus Output Through Runoff on a Red Soil Slope Under
Natural Rainfall Conditions].
AB - The development of agriculture in the red soil sloping uplands has been
increasingly restricted by low water availability, high temperatures, and low
fertilizer use efficiency. Subsurface flow has a significant influence on runoff
generation, nutrient loss, and soil erosion. The rainfall-runoff process makes it
easy for nutrients on the sloping land to enter water bodies through subsurface
flow mainly in the liquid phase, which may lead to environmental problems such as
eutrophication and groundwater pollution. Phosphorus as one of the common
nutrients causing eutrophication is immobile in the soil because it is easily
absorbed and fixed by soil particles. Thus, the principal pathway of phosphorus
release from the soil is the surface flow. In some regions, sufficient and
concentrated rainfall results in the surface-subsurface flow that enhances
phosphorus migration. Recently, researchers have studied the migration patterns
of red soil phosphorus through surface flow and the impact factors arising from
these migrations, as well as the generation of subsurface flow and its influence
on phosphorus outputs. However, there are relatively few investigations that have
comprehensively considered the influence of both surface flow and subsurface flow
on the migration of red soil phosphorus. In order to investigate the
characteristics of phosphorus loss through runoff under natural rainfall, a large
scale field lysimeter experiment was conducted with three treatments i.e., grass
cover (GC), litter mulch (LM), and bare land (BL) on a red soil slope land in
southeast China. Phosphorus loss through surface flow, interflow at different
soil layers (30 cm and 60 cm), and groundwater flow (at 105 cm depth) was
observed under each natural precipitation event over a one-year period. The
results showed that:1 The concentrations of total P (TP) and dissoluble P (DP) in
surface flow were slightly higher than those in interflow and groundwater flow;
the concentrations of TP and DP showed a gradual downward trend with the increase
in soil depth. The total amount of TP runoff loss was ordered as BL (1.61 kg.hm
2) > LM (1.33 kg.hm-2) > GC(0.82 kg.hm-2). 2 Surface flow, interflow, and
groundwater contributed to 57%, 6%, and 37%, respectively, of the phosphorus
runoff loss on BL plot; surface runoff was the main pathway of phosphorus loss.
Groundwater flow was the crucial route of phosphorus runoff loss once a
vegetation cover was in place; groundwater flow contributed to more than 71% of
the phosphorus runoff loss while the surface flow contributed less than 14%. 3
Particulate phosphorus was the primary pattern of phosphorus transport which
accounted for 64%-97% of the total amount of phosphorus runoff loss. The effect
of phosphorus loss through groundwater flow cannot be neglected on the red soil
slope land. The loss load of phosphorus through runoff can be controlled by grass
cover and litter mulch treatments, whereas the concentrations of phosphorus in
runoff do not significantly reduce.
PMID- 29965202
TI - [Occurrence, Distribution and Health Risk of the Phthalate Esters in Riparian
Soil in the Fluctuating Zone of the Three Gorges Reservoir].
AB - Soil samples were collected in the fluctuating zone of the Three Gorges Reservoir
to analyze the concentrations and distribution of phthalate esters (PAEs) using
ultra performance liquid chromatography-quadrupole-time of flight mass
spectrometry (UPLC-Q-TOF-MS). Meanwhile, the interrelationships among the PAE
congeners were analyzed and the potential sources of PAEs in soil were determined
by the correlation analysis and principal component analysis. The results showed
that the concentrations of ?PAEs ranged from 322.0-737.3 ng.g-1 dry weight, with
a mean value of 497.2 ng.g-1 dry weight, which lies at the low end of the
worldwide Figures. DIBP was the most abundant PAEs congener, followed by DBP and
DEHP, contributing to 94.5% of the total PAEs. However, DEHP was not the main
pollutant in this study compared to other studies, which might be ascribed to the
release of DEHP from the flooded soil to the surrounding water but the
degradation by microorganisms in the soil cannot be completely ruled out.
Significant interrelationships were observed among DMP, DEP, DBP, and DIBP. The
principal component analysis showed that DMP, DEP, DBP, and DIBP may have similar
sources. In this study, the daily intake dose was lower than the reference dose
(RfD) proposed by the United States Environmental Protection Agency (USEPA), and
the carcinogenic risk of six PAE congeners was far below the tolerable values
proposed by the USEPA. Nevertheless, the daily intake dose of DBP accounted for
60% to 84% of total PAEs; thus, more attention should be paid to the potential
health risks of DBP.
PMID- 29965203
TI - [Seasonal Distribution, Composition, and Source Apportionment of Polycyclic
Aromatic Hydrocarbons and Organochlorine Pesticides in the Main Stream of the
Luanhe River].
AB - Occurrence of 17 polycyclic aromatic hydrocarbons (PAHs) and 15 persistent
organochlorine pesticides (OCPs) were analyzed by gas chromatography coupled to
tandem mass spectrometry (GC/MS/MS) during the spring and summer of 2015 in
surface water at 14 sampling sites in the mainstream of the Luanhe River to
elucidate their seasonal distribution, composition, and potential sources.
Results showed that total PAH concentrations in the surface water of the Luanhe
River ranged from 33.33 ng.L-1 to 90.65 ng.L-1(52.64 ng.L-1 in average) in spring
and 147.68 ng.L-1 to 252.68 ng.L-1 (169.88 ng.L-1 in average) in summer,
respectively, and total concentrations of OCPs ranged from <0.08 ng.L-1 to 3.48
ng.L-1 (1.19 ng.L-1 in average) in spring and <0.08 to 5.47 ng.L-1(1.02 ng.L-1 in
average) in summer, respectively. Seasonal pollution characteristics of PAHs in
surface water during two different seasons showed that total PAH concentrations
were much higher in summer than in spring at each sampling site on the Luanhe
River. While seasonal pollution characteristics of OCPs showed that total OCP
concentrations were much lower in spring than in summer at six sites including
Luanxian, Daheiting reservoir dam, Panjiakou Village, Guojiatun, Qujiawan, and
Baichengzi, and were higher in spring than in summer at the remaining eight
sites. From the perspective of spatial and temporal variations in the composition
patterns of PAHs and OCPs in surface water of the Luanhe River, the low and
middle ring species of PAHs were dominant in spring and summer and the proportion
of PAHs with different rings showed significant differences. Three-ring PAHs
dominated the samples with 51.18% and 67.55% (61.39% on average) of total PAHs in
spring, and four-ring and two-ring PAHs accounted for 11.78%-33.94% (20.97% on
average) and 13.31%-27.12% (16.94% on average), respectively. In the summer, In
the summer, naphthalene(Nap) was the main component of total PAHs at each
sampling site and PAHs were predominated by two-ring compounds with 77.08% and
90.62% (83.34% on average) of the total, and by three-ring and four-ring
compounds with 7.09%-15.22% (12.40% on average) and 2.23%-7.49% (3.97% on
average), respectively. Only the residues of hexachlorocyclohexanes(HCHs) and
dichlorodiphenyltrichloroethanes(DDTs) were detected in surface water of the
Luanhe River at different degrees and HCHs were the dominant compounds. beta-HCH
was the main pollutant at most sampling sites with 43.78% and 70.09% (56.25% on
average) of total HCHs in the spring and with 53.63% and 64.31% (58.37% on
average) in the summer. alpha-HCH and gamma-HCH were abundant at other sampling
sites. Source analysis based on the isomer ratios indicated that PAHs in the
Luanhe River mainly originated from combustion sources and also likely from
petroleum processes. Ratios of OCPs confirmed that historical residues and long
range atmospheric transport were the major sources of HCHs in the study area, and
new sources of lindane or gamma-HCH existed at Wulongji and Sandaohezi in the
spring and Daheting reservoir dam in the summer. Fresh inputs at the Panjiakou
reservoir dam, Sandaohezi, Waigoumenzi, Baichengzi, Zhenglanqi, and the
Shandianhe reservoir, and environmental residues at Jianggezhuang and Guojiatun
were the major sources of DDTs. Concentrations of single PAHs in surface water of
the Luanhe River did not exceed the water quality standards of China and other
countries except that chrysene(Chr) exceeded the United States national water
quality standard. Individual PAHs did not exceed any safety guidelines for
aquatic organisms that are exposed to PAHs in water but total concentrations of
PAHs exceeded the threshold limits set by the United States Environmental
Protection Agency (EPA) and the European Union. This result indicated that
consuming fish and other aquatic animals might pose a potential threat to human
health due to the bioaccumulation of PAHs in aquatic organisms. The
concentrations of OCPs in surface water of the Luanhe River did not exceed any
water quality standards or the aquatic life threshold limits for freshwater
developed by the EPA. However, the concentrations of alpha-HCH at Jianggezhuang,
Wulongji, Qujiawan, and Baichengziand sites in the spring and at the Panjiakou
reservoir dam, Panjiakou village, Qujiawan, and Baichengzi sites in the summer,
and concentrations of p,p'-DDD at the Shandianhe reservoir and p,p'-DDE at
Jianggezhuang, Sandaohezi, Guojiatun, and Shandianhe reservoir in the spring
exceeded the human health ambient water quality criteria limit developed by the
EPA. This result suggests that alpha-HCH, p,p'-DDE, and p,p'-DDD pose a potential
health risk to the residents who live near the sampling sites on the Luanhe
River.
PMID- 29965204
TI - [Occurrence and Human Exposure Risk Assessment of Organophosphate Esters in
Drinking Water in the Weifang Binhai Economic-Technological Development Area].
AB - Concentrations and composition of six organophosphate esters (OPEs) in drinking
water in the Weifang Binhai Economic-Technological Development Area were detected
by solid phase extraction-gas chromatography-triple quadrupole mass spectrometry
(SPE-GC-MS/MS). The correlations of OPEs in drinking water and pooled serum
samples from the Weifang Binhai Economic-Technological Development Area were
analyzed. The health risk posed by OPEs in drinking water was evaluated using the
health risk assessment model recommended by the United States Environmental
Protection Agency (USEPA). The results showed that ?6OPEs concentrations in the
tap water samples ranged from 162-253 ng.L-1, while ?6OPEs concentrations in
groundwater ranged from 3.52-13.9 ng.L-1, two orders of magnitude lower than that
in the tap water. Tris(2-chloroethyl)phosphate (TCEP) was the dominant OPE in the
tap water samples, with the median level accounting for 94.81% of the ?6OPEs.
Triphenyl phosphate (TPhP) was the dominant OPE in groundwater, with the median
level accounting for 47.55% of the ?6OPEs. The composition of OPEs in the human
mixed serum collected in 2011 and 2015 was strongly correlated with that in the
tap water (r=0.990, P<0.01 and r=0.997, P<0.01, respectively). This indicates the
significant contribution of OPEs in drinking water to OPEs in human serum. The
daily intake (DI) of OPEs via drinking water was 0.26-7.48 ng.(kg.d)-1 and the
non-cancer risk hazard quotient (HQ) of OPEs in drinking water ranged from 10
5.81-10-2.43, indicating a negligible non-cancer risk to the local residents
exposed to OPEs through drinking water. The carcinogenic risks posed by TCEP in
drinking water ranged from 10-8.82-10-6.79, which was lower than the theoretical
threshold (Risk=10-6.00), while the carcinogenic risk of TCEP in tap water was
higher than that in groundwater.
PMID- 29965205
TI - [Contamination Characteristics and Human Exposure to Organophosphate Flame
Retardants in Road Dust from Suzhou City].
AB - The contamination levels and distribution characteristics of four organophosphate
flame retardants (OPFRs) in 25 outdoor dust samples collected in Suzhou were
quantitatively analyzed by gas chromatography-mass spectrometry (GC-MS). The
exposure to OPFRs via ingestion and inhalation of dust were also estimated for
adults, children, and professional street sweepers. Four types of OPFRs were
detected in all dust samples at different levels; the total OPFRs concentrations
ranged from non-detected (ND) to 8901.66 ng.g-1, with a median of 1039.21 ng.g-1.
The concentrations of TCPP, TBEP, TDCPP, and TCEP were in the range of 0-6931.46,
0-2021.15, 0-788.44, and 0-62.16 ng.g-1, respectively. The daily intake of ?OPEs
under a high dust ingestion scenario was 125.68, 915.78, and 6314.16 pg.kg-1 for
adults, children, and professional street sweepers, respectively. The estimated
exposure of children to ?OPEs was six times higher than that of adults. However,
the daily intake of OPFRs via dust inhalation was 3.07E-02, 1.89E-02, and 1.54E
01 pg.kg-1 for adults, children, and professional street sweepers, respectively.
These findings indicated that the occurrence of OPFRs in the dust poses a
significant risk to children and professional street sweepers.
PMID- 29965206
TI - [Cancer Risk of Human Intake of PAH-Contaminated Particles Based on Hand-to-Mouth
Activities].
AB - The health risk of residents exposed to PAH-contaminated outdoor soil and indoor
dust particles via hand-to-mouth transfer was estimated by developing
probabilistic risk models. The cancer risk was assessed by applying the Monte
Carlo method. The results showed that toddlers, children, and teens were at
greatest risk of exposure, followed by infants, adults, and seniors. The
probability of exceeding the acceptable level 10-6 was 2% for infants, 5% for
toddlers and teens (none of the values were larger than the upper limit 10-4),
15% for children (0.1% of the values were larger than 10-4); and 1% and 0.1% for
adults and seniors, respectively. Indoor dust posed a more serious threat than
outdoor soil, which accounted for 91% of the total risk; indoor hard surfaces
were the main sources of indoor dust with a contribution of 65%. The most
influential variables were the frequency of hand-to-mouth events (FQ),
benzo[a]pyrene from indoor dust (PEFj), dust surface load on horizontal soft
surfaces (DSLSS) and hard surfaces (DSLHS), and saliva extraction factor (SE).
PMID- 29965207
TI - [Spatio-temporal Evolution of Groundwater Vulnerability Based on Spatial
Autocorrelation].
AB - The distribution patterns of human activities affecting groundwater vulnerability
vary with time. Studying the temporal and spatial changes in groundwater
vulnerability, exploring the distribution characteristics of each period, and
predicting the trends of development are important to formulate an effective
development plan and reduce the risk of groundwater pollution at the same time.
Based on the hydrogeological data as well as humanities and social data for 2004,
2010, and 2016 for the Chaoyang District of Beijing, a comprehensive evaluation
model considering the human factors such as the land use types was established
using the DRASTIC model. The spatiotemporal pattern of groundwater vulnerability
was quantitatively characterized by calculating the Global Moran's I and Getis
Ord Gi* index, and the distribution characteristics and variations in groundwater
vulnerability were analyzed by the centroid of the G index and the standard
deviation ellipse of the study area. The results indicate that in 2004, 2010, and
2016, the areas of high vulnerability have gradually reduced. The groundwater
vulnerability in the study area shows a strong spatial aggregation; high
concentration areas are mainly distributed in the northeast and southwest
regions. The vulnerability of the northeast region has been decreasing each year,
while the vulnerability of the northwest region has not changed much. The main
reasons are the land use changes and the reductions in fertilizer use.
PMID- 29965208
TI - [Preparation of Ag-AgI/CN/MA Composites and Their Visible-light Photocatalytic
Performance].
AB - Ag-AgI/CN/MA photocatalysts were prepared by coupling graphitic carbon nitride
(CN) with AgI/gamma-Al2O3(AgI/MA) through a thermal polymerization method and Ag
nanoparticles were deposited by photoreduction. The catalysts were characterized
by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), field
emission scanning electron microscopy (FESEM), UV-vis diffuse reflectance spectra
(UV-vis DRS), and transmission electron microscopy (TEM). The photocatalytic
performance of different catalysts was evaluated under visible light irradiation
(lambda>420 nm). The effects of different conditions such as pH and catalyst
dosage on photoreactions were also investigated. The results showed that Ag+ and
Ag0 coexisted on the surface of the catalyst and Ag and AgI nanoparticles were
uniformly distributed on the surface of CN. Compared with CN and Ag-AgI/MA, Ag
AgI/CN/MA composites exhibited better visible-light photocatalytic activity and
stability, and the release of silver ions was significantly suppressed. At the
catalyst dosage of 1 g.L-1 and pH=7, Ag-AgI/CN/MA-2 exhibited the optimal
photocatalytic performance. Ag-AgI/CN/MA-2 also showed high photoactivity for the
degradation of dyes with different charges, such as rhodamine B (RhB), methyl red
(MR) and congo red (CR).
PMID- 29965209
TI - [Effect of Eichhornia crassipes on Ammoxidation and Denitrification
Microorganisms in Eutrophic Freshwaters].
AB - The water hyacinth, Eichhornia crassipes, is widely used for the ecological
restoration of eutrophic freshwater bodies, but little is known about its
microbial interactions and nitrogen removal potential. In this study, we compared
the relative importance of E. crassipes and bacteria in nitrogen removal. We also
examined the plant's ability to modulate the abundance and diversity of
nitrifying and denitrifying bacteria. Nitrogen removal and the genetic potential
for nitrification and denitrification, determined using quantitative polymerase
chain reactions (qPCRs) of the nitrification gene amoA and the denitrification
genes nirS/K, were evaluated in microcosms containing water from a eutrophic lake
with or without E. crassipes. The results showed that total nitrogen (TN) losses
on day 70 of the experiment were similar in all treatments but the uptake by E.
crassipes resulted in the rapid (within 24 h) removal of TN and NH4+-N. In
microcosms containing E. crassipes, the abundance of amoA increased whereas the
abundances of nirS/K decreased. The T-RFLP (terminal restriction fragment length
polymorphism) profiles showed that Nitrosomonas dominated the ammonia-oxidizing
prokaryotes, based on the DNA and RNA levels of the targeted genes. The E.
crassipes cultivation can be used to achieve fast and efficient reductions in
NH4+-N concentrations in eutrophic water bodies. While this aquatic macrophyte
may not be essential to N removal, considering the potential toxicity of NH4+-N,
both aquaphytes and microbes should be fully exploited in the restoration of
freshwater ecosystems.
PMID- 29965210
TI - [Utilization of Copper (II) Wastewater for Enhancing the Treatment of Chromium
(VI) Wastewater in Microbial Fuel Cells].
AB - The effect of copper (II) wastewater addition on the treatment of chromium (VI)
wastewater in dual-chamber microbial fuel cells (MFCs) was investigated for
different Cr(VI)/Cu(II) concentration ratios (2:1, 1:1, 1:2, 1:4) and external
resistances (10, 500, 1000, 2000 Omega). The results demonstrated that the
addition of Cu(II) and Cr(VI) into the cathode chamber of MFCs could enhance the
Cr(VI) removal efficiency. The Cr(VI) removal efficiency increased with the
increase in the Cr(VI)/Cu(II) concentration ratio. The Cu(II) on the Cr(VI)
removal efficiencies increased with the decrease of external resistance. The
highest Cr(VI) removal efficiency achieved was 91.00% in MFC at the Cr(VI)/Cu(II)
concentration ratio of 1:4 and external resistance of 10 Omega, which was 132.57%
higher than the MFC with Cr(VI) only (39.13%). The scanning electron microscopy
with coupled energy dispersive spectroscopy (SEM-EDS) and X-ray photoelectron
spectroscopy (XPS) analyses of the cathode electrode at the end of the
experiments indicated that Cr(VI) reduced to non-conductive Cr(III) deposits
(Cr2O3) on the cathode electrode, resulting in cathode deactivation which blocked
the electron transfer. However, the addition of Cu(II) could improve the
electrical conductivity of the cathode due to its conductive reduzates (copper
and Cu2O) on the cathode which could reduce the cathode deactivation and
subsequently enhance the Cr(VI) removal efficiency.
PMID- 29965211
TI - [Efficiency and Microecology of a Soil Infiltration System with High Hydraulic
Loading for the Treatment of Swine Wastewater].
AB - The swine wastewater after treated with an anaerobic reactor was used to
investigate the removal efficiency of COD, ammonia nitrogen, and total nitrogen
in an ecological high hydraulic loading soil infiltration system. Meanwhile, the
microbial community structure and the contents of the catalase, urease, and
nitrate reductase were analyzed. The results showed that with the hydraulic load
of 11 cm.d-1 and the influent COD concentration of 700 mg.L-1, the removal rate
of COD was 78.8%, 63.0%, and 92.6%for the first land infiltration column, the
secondary land infiltration column, and the total system, respectively. When the
hydraulic load increased to 22 cm.d-1; the total removal rate of COD was also
above 90.0%. The system was more significant for ammonia nitrogen removal. The
removal rate of ammonia nitrogen reached approximately 99%. The contents of
catalase were 1.899, 0.990, and 0.323 mL.g-1 at the upper, middle, and bottom
sections of the system, respectively. The organic matter in the swine wastewater
was removed at the upper and middle of the system. On the secondary soil
infiltration system, the content of nitrate reductase was 3.453, 3.831, and 1.971
mL.g-1, respectively. Denitrification mainly occurred in the upper and middle of
the secondary soil infiltration system. Gram Negative and Gram Positive bacteria
were given priority in the soil infiltration system. Especially, arbuscular
mycorrhizal fungi and Actinomycetes dominated the secondary soil infiltration
system. The system provides a guarantee for the removal of the refractory organic
compounds from the swine wastewater.
PMID- 29965212
TI - [Effects of Bacteria on the Growth of and Lipid Accumulation in Chlorella
pyrenoidosa Cultivated in Municipal Wastewater].
AB - Cultivating microalgae using municipal wastewater can treat wastewater and
recover algal biofuel as an energy source. Wastewater provides necessary
nutrients such as nitrogen, phosphorus, and water for microalgal growth. Due to
the complexity of the components of municipal wastewater and the complex
symbiotic and antagonistic relationship between microalgae and bacteria, it is
necessary to select the suitable dominant bacterial species that can promote the
microalgae to achieve high lipid production and algal biofuel production using
municipal wastewater. Based on the microalgal growth and lipid production, we
selected Photosynthetic bacteria and W4 bacteria from 13 different types of
bacteria and analyzed the microbial community structure of the municipal
wastewater at the end of the microalgal culture cycle. Laboratory test results
showed that the amount of lipid production by Photosynthetic bacteria and W4 was
0.114 g.L-1 and 0.113 g.L-1, which is 22.58% and 21.50% higher than the
production by the control group, respectively. According to the gas
chromatography (GC) analysis of the lipids, Photosynthetic bacteria and W4
bacteria exerted a relatively low influence on the composition of fatty acids of
Chlorella pyrenoidosa but increased the content of monounsaturated fatty acids
that improve the grade of biodiesel. The results of the analysis of microbial
community structure of the municipal wastewater showed that Photosynthetic and W4
bacteria reduced the richness and diversity of bacterial communities and have the
potential to become the dominant bacterial community.
PMID- 29965213
TI - [Enhanced Antibiotic Resistant Bacteria Removal from Wastewater Treatment Plant
by Different Disinfection Technologies].
AB - Based on the removal of total heterotrophic bacteria (HPC) and antibiotic
resistant bacteria (ARB), including the ampicillin resistant bacteria (AMP),
erythromycin resistant bacteria (ERY), tetracycline resistant bacteria (TET),
kanamycin resistant bacteria (KAN), and ciprofloxacin resistant bacteria (CIP),
this study investigates the enhanced removal performance of ARB by different
disinfection technologies. The experimental results showed that ARB removal by
ultraviolet (UV) disinfection from the wastewater treatment plant (WWTP) was only
18.2%-40.9% and AMP was the highest in content. ERY could be selectively removed
by different disinfection technologies; however, there was no distinguished
selective removal performance for other four types of ARB (P<0.05). For ARB, COD
and NH4+-N removal, the optimal ozone, chlorination, and UV concentration or
dosage were 5.0 mg.L-1, 25.0 mg.L-1, and 45.0 mJ.cm-2, respectively, and the
corresponding ARB removal efficiencies were 45.5%-74.5%, 66.1%-85.5%, and 68.6%
85.5%. Furthermore, the combined UV and chlorine treatment could achieve better
ARB removal performance.
PMID- 29965214
TI - [Coking Wastewater Treatment Efficiency and Comparison of Acute Toxicity
Characteristics of the AnMBR-A-MBR and A2-MBR Processes].
AB - Coking wastewater contains high-strength refractory organic pollutants and is
commonly treated by biological treatment processes. To improve the efficiency of
biological treatment, two laboratory scale processes, anaerobic membrane
bioreactor/anoxic/aerobic membrane bioreactor (AnMBR-A-MBR) and
anaerobic/anoxic/aerobic membrane bioreactor (A2-MBR), were developed for coking
wastewater treatment. The removal of main pollutants and the stability of
different pollutant loadings were compared under the optimum operating
conditions. Acute toxicity distribution, variations, and toxic matter
characteristics of the two processes were investigated by solid-phase extraction,
components separation, the luminous bacteria Q67 test, and three-dimensional
fluorescence spectrometry. The results showed that the organic pollutant removal
rate of AnMBR was 15.3%, which was significantly higher than the anaerobic stage
of the A2-MBR system (3.4%), and the AnMBR-A-MBR system had greater resistance to
pollutant loading. Acute toxicity of AnMBR-A-MBR system in each stage effluent
was lower than the A2-MBR system and the total toxic unit removal rate of both
were 85.2% and 79.2%, respectively. The acute toxicity of the polar component in
each stage effluent was the highest, and the polar and mid-polar components
contributed to the majority of the toxicity. The toxicity of each stage effluent
mainly originated from Region II aromatic protein analogues, which could be the
main acute toxicity substances of the polar component.
PMID- 29965215
TI - [Stability of the CANON Process Based on Real-Time Control Technologies].
AB - In order to achieve the optimization of the CANON process, ensuring the stability
of water quality and increasing the removal rate of ammonia nitrogen, the
stability of CANON process water quality under real-time control was studied in
the SBR reactor. During the experiment, the temperature was controlled at 30C+/
1C and the pH was 7-8, based on the corresponding relationship between indirect
parameters and nitrogen pollutants, the real-time control strategy was
formulated. The results showed that when the influent ammonia nitrogen
concentration was 917-1540 mg.L-1, the residual ammonia nitrogen concentration of
6 mg.L-1 can be used as the control parameter to meet the requirements of process
stability but the ammonia nitrogen sensor had many problems such as high costs
and large errors. The characteristic points and platforms of pH, DO, and ORP
value can be the automatic control parameters, which can maintain the long-term
stable operation of the CANON process and ensure that the average ammonia
nitrogen removal rate is above 99% and the effluent quality is stable.
PMID- 29965216
TI - [Improving Nitrogen and Phosphorus Removal from Reclaimed Water Using a Novel
Sulfur/Iron Composite Filler].
AB - In order to improve the ability of denitrification and phosphorus removal from
reclaimed water, a novel composite filler was prepared using sulfur powder and
sponge iron powder, and a comparative experiment was constructed at different
HRT(hydraulic retention time) and C/N(carbon-nitrogen ratio) conditions between
the novel filler and the composite filler. The results showed that the efficiency
of nitrogen and phosphorus removal on the novel filler was higher than that on
the grain filler (more than 30% higher at HRT=4 h and C/N=1). Moreover, based on
the 16S rRNA gene clone library, the denitrification system in the two reactors
included sulfur autotrophic denitrification bacteria and heterotrophic
denitrification bacteria, while the proportion of sulfur autotrophic
denitrification bacteria in the novel filler system was higher. The dominant
bacteria in the novel filler and composite filler were Sulfurimonas and
Acinetobacter, respectively.
PMID- 29965217
TI - [Start-up and Capacity Enhancement of a Partial Nitrification Pilot Reactor in
Continuous Flow].
AB - The continuous flow reactor was used to treat simulated ammonia nitrogen
wastewater by inoculating the sludge after filtration and adding a suspended
filler. Regulations of free ammonia (FA), free nitrous acid (FNA), and dissolved
oxygen (DO) in the reactor were the key to achieving a successful start-up of the
pilot scale nitrosation reactor. The results show that the enrichment of ammonium
oxidizing bacteria (AOB) and the elimination of nitrite oxidizing bacteria (NOB)
are achieved by adjusting the operational mode of high DO, low DO, FA, and FNA in
the reactor operation. The nitrite production rate (NPR) in the reactor was 1.27
kg.(m3.d)-1 and the nitrogen accumulation rate (NAR) was stable at 98% at the end
of the start-up period. qPCR was used to study the difference in the functional
microorganisms (AOB, NOB) between the beginning and the end of the start-up
period. The results show that the copy number of microbial AOB grew from 5.3*109
copies.mL-1 to 1.6*1011 copies.mL-1. The copy number of NOB decreased from
1.1*1010 copies.mL-1 to 1.2*109 copies.mL-1, because of the joint regulation of
DO, FA, FNA to suppress NOB.
PMID- 29965218
TI - [Quick Start-up Performance of Combined ANAMMOX Reactor Based on Different
Inoculated Sludge Types].
AB - In order to determine the optimal sludge source of anaerobic ammonium oxidation
(ANAMMOX) and the rapid formation of ANAMMOX granular sludge, two CAMBRs
(combined ABR and MBR) were compared for ANAMMOX enrichment with different
inoculated sludge types, the anaerobic granular sludge (R1) and flocculent
denitrifying sludge (R2). The results showed that ANAMMOX was successfully
initiated after 45 d (R1) and 60 d (R2) in both reactors, respectively. The
enrichment processes are divided into three different phases, lag phase, activity
elevation phase, and stationary phase but the removal rules of nitrogen in each
phase were different. In the steady phase, the average removal rates of NH4+-N
and NO2--N were higher than 95%. In addition, the red ANAMMOX granular sludge
with the main diameter of 0.8-1.6 mm was formed in R1 while the flocculent sludge
and irregular block with a low degree of granulation were mainly developed in R2.
The phenomenon of red granular sludge floating in the two reactors was also
observed. The quantitative relationship analysis between NH4+-N, NO2-N, and NO3-
N showed the occurrence of nitrate-dependent ANAMMOX, which resulted in the
oxidation of excess ammonia and the typical nitrite-dependent ANAMMOX occurred in
R2.
PMID- 29965219
TI - [Effect of Two-Stage Aeration on Nitrogen Removal Performance of Aerobic Granular
Sludge].
AB - Four mini experiments were conducted at different conditions. The heterotrophic
microorganisms on the aerobic granular sludge surface consumed organic compounds
at the initial stage of aeration. The denitrification rate and the efficiency of
NO2--N and NO3--N removal were relatively low. Therefore, under the normal
temperature conditions (20-23C), aerobic granular sludge sequencing batch reactor
(SBR) was operated in the two-stage aeration mode(first in low aeration then in
high aeration mode). The low aeration time were carried out at 1, 2 and 3 hours
stages respectively, and the characteristics of the granular sludge and its
effects on microorganisms were analyzed by scanning electron microscopy (SEM) and
fluorescence in situ hybridization (FISH) technique. The results show that the
increase in the aerobic granular sludge (AGS) particle size improved the
denitrification capacity; the denitrification rate of NO2--N was the highest at
low aeration mode with 2 h and reached 9.66 mg.(g.h)-1. The accumulation rate of
nitrite increased to 77.84% and the total nitrogen removal rate to 70%. The
bacterial count inside the granular sludge increased and they were mainly cocci,
bacillus, and ellipsoidal bacteria. Moreover, the proportion of ammonia-oxidizing
bacteria in total bacterial count increased from 13.70% to 15.40%. Therefore, the
two-stage aeration process achieved shortened simultaneous nitrification and
denitrification processes and showed a good denitrification performance.
PMID- 29965221
TI - [Comparision of Ecological Risk Assessment Based on the Total Amount and
Speciation Distribution of Heavy Metals in Soil:A Case Study for Longyan City,
Fujian Province].
AB - A total of 110 topsoil samples and 61 crop samples along the Lantian-Yangdong
Villages were collected in Shizhong, Longyan City. The total amount and
speciation of heavy metals(Pb, Cd, As) in soil and crops were determined. The
characteristics of the absorption of heavy metals by specific crops in the study
area were analyzed, and a new method of risk assessment based on the heavy metal
speciation and its bioavailability was established by statistical analysis. This
new method was used to evaluate the soil ecological risk and to compare it with
the traditional method of potential ecological risk index (RI). The results
indicated that the Lantian-Yangdong Villages were located in an area where Pb,
Cd, and As mainly originate from the natural soil parent material with weak human
disturbance. There was no significant Pb or As pollution in the whole region. Cd
was the main pollutant with low pollution intensity. Four types of biological
components except for the residual form followed the order of Cd(53.28%) >
Pb(43.28%) > As(30.71%). Correlation and regression analyses of total metal
concentrations, heavy metal speciation, and crop uptake in the study area showed
that the correlations between the total amount of heavy metals and the ion
exchange state, carbonate state, and other active forms were low; the results
even showed nonlinear relationships between those variables.The ion exchange
state had the greatest effect on the absorption of Pb, Cd, and As by coix seed
and rice. From the perspective of bioavailability, the new method based on the
heavy metal speciation was more accurate than the traditional method based on the
total amount of heavy metals.
PMID- 29965220
TI - [Construction of a High Efficiency Anaerobic Digestion System for Vinegar
Residue].
AB - The model of high solid anaerobic digestion was used by improving the degree of
homogeneity of the reaction system and biogas slurry reflux to gradually increase
the material load. The vinegar residue-efficient anaerobic digestion system was
successfully constructed without pretreatment.The optimum anaerobic digestibility
was observed when the material loading of the reaction system reached 6.15
g.(L.d)-1, when the amount of biogas produced per unit of dry material was 396
mL.g-1, and the amount of methane produced per unit of dry material was 211 mL.g
1. The degradation rate of hemicellulose reached 63.66%, which was the main
reason for the improvement of anaerobic digestion performance. The degradation
rates of cellulose and lignin were 21.46% and 24.43%, respectively. The lower
degradation efficiency was mainly due to the complicated degradation of the
benzene ring structure in lignin and hindered hydrolysis of cellulose, which had
a shielding effect on cellulose degradation.
PMID- 29965222
TI - [Heavy Metal Contamination of Soils and Crops near a Zinc Smelter].
AB - To evaluate the influence of mining activities on heavy metal contamination and
health risks in a zinc-smelting area in Guizhou Province, Pb, Cd, Zn, and Cu in
agriculture soils and dominant crops were monitored and analyzed. A single factor
pollution index and a comprehensive pollution index were calculated to assess the
quality of soils and crops. Furthermore, the potential ecological risks of the
four heavy metals in soils and crops were evaluated using the potential
ecological risk index (RI). The potential health risks to adults and children
induced by the intake of these heavy metals through consumption of crops were
evaluated using the hazard quotient (HQ). The results showed that:1The farmlands
in the zinc-smelting area were contaminated by heavy metals; the most polluted
farm land was corn fields followed by paddy fields and wheat fields. The order of
the heavy metal concentrations was Cd > Cu > Zn > Pb. The Nemero index of corn
fields was higher than the threshold value of heavy pollution and was higher than
that of the paddy and wheat fields. Cd contributed most to the integrated
pollution index. 2The very high ecological risk was posed by Cd followed by Pb,
Cu, and Zn. The results of the potential ecological risk assessment showed that
1.41% of the sites were classified as low risk, 21.1% classified as medium risk,
35.2% as high risk, and 42.3% as extremely high risk. 3The average concentrations
of Pb, Cd, Zn, and Cu in rice were 0.145, 0.017, 16.97, and 2.704 mg.kg-1,
respectively. The average concentrations of Pb, Cd, Zn, and Cu in corn were
0.094, 0.055, 26.81, and 4.464 mg.kg-1, respectively. The average concentrations
of Pb, Cd, Zn, and Cu in wheat were 0.048, 0.085, 35.37, and 5.426 mg.kg-1,
respectively.4Rice, corn, and wheat from the study area were subjected to
pollution at different degrees. Among the three crops studied, wheat was polluted
most heavily, followed by rice and corn. Contamination levels of rice and corn
were safe, whereas the contamination of wheat reached alarming levels. 5The daily
intake of individual heavy metals from food was below the standard exposure dose
set by the United States Environmental Protection Agency. In addition, the
assessment results for the comprehensive health risk index for the three crops
indicate that the contamination of heavy metals poses health risks to adults and
children by food ingestion. 6 Positive correlations were not observed between
farmlands and crops.
PMID- 29965223
TI - [Characteristics and Influencing Factors of CH4 Emissions from the Drawdown Area
of the Three Gorges Reservoir].
AB - Five levels (180 m, 175 m, 165 m, 155 m, and 140 m) in a typical drawdown area in
Wangjiagou in the Three Gorges Reservoir were selected to study CH4 emissions
from subtropical reservoirs. The experimental period lasted two years from
September 2010 to August 2012. The methods of static opaque chambers during the
drainage period and floating chambers during flooding period were used in this
study. The elevations of 175 m, 165 m, and 155 m were all located in the drawdown
area, whereas the 180 m elevation was located in the land and never flooded. The
140 m elevation was permanently flooded and used as a control area. The results
showed that the CH4 fluxes showed no significant trends at 175 m and 165 m in the
first year of the experiment, while the fluxes showed a single peak pattern with
the climax in the summer at 155 m and 140 m. At 175 m, the CH4 emissions showed a
single peak pattern with the climax during its flooding period, and then showed
not regular CH4 emission sources or sinks alternately in the second year, whereas
the CH4 fluxes at 165 m, 155 m, and 140 m presented a single-peak shape with
winter climax. During the entire observation period, the CH4 emission fluxes at
180 m were stable and showed no obvious peaks. In addition, CH4 fluxes were
higher during the flooding period than in the drainage period at 175 m, 165 m,
and 155 m.The order of the annual CH4 cumulative emissions at the five elevations
was 140 m (99.58 kg.hm-2) > 155 m (82.98 kg.hm-2) > 165 m (65.38 kg.hm-2) > 180 m
(6.32 kg.hm-2) > 175 m (4.27kg.hm-2), suggesting that the soil was more conducive
to CH4 production when the flooding period was longer. Correlation analysis
indicated that there were no significant correlations between CH4 fluxes and the
soil carbon component and pH on land and during the drainage period but CH4
fluxes increased with the increase in soil water content. There was a significant
linear negative correlation between CH4 emissions from the gas-water interface at
140 m and in water. The soil moisture content was one of the key factors
affecting the CH4 fluxes during the drainage period, while during flooding
period, the CH4 fluxes were regulated by flooding depth.
PMID- 29965224
TI - [Effects of Plastic Film Mulching on Nitrous Oxide Emissions from a Vegetable
Field].
AB - Considering the common cropping system (chili-radish rotation) in Southwest
China, the objective of this study is to explore the effect of plastic film
mulching on N2O flux, N2O concentrations in the soil profile, soil temperature,
and humidity from a vegetable field. The method of the static opaque chamber was
used and the experimental period lasted for one year. The results showed that the
average flux of N2O was 1000.0 MUg.(m2.h)-1 in the conventional treatment and
400.6 MUg.(m2.h)-1 in the film mulching treatment during the chili growing
period. The N2O flux of the film mulching treatment was significantly lower than
that of conventional treatment (P<0.05). However, in the radish growing season,
the N2O flux of the film mulching treatment was higher than that of conventional
treatment, but the difference between the two treatments was not significant
(P>0.05). N2O concentrations in the soil profile of the two treatments both
increased with the increase in soil depth. The N2O concentrations showed
significant correlations among the different soil profiles of each treatment;
meanwhile, there was also a significant correlation between soil N2O
concentrations at the same soil depth in different treatments. There was a
significant positive correlation between the N2O concentration in different
profiles and N2O fluxes in surface soils in the conventional treatment, but the
N2O flux under the plastic mulching film treatment was only positively correlated
with the N2O concentrations of 30 cm deep soil. The soil moisture and temperature
observations showed that the effect of plastic film mulching on soil temperature
was more significant in summer and the soil moisture was more prominent in autumn
and winter. However, the results of the correlation analysis and principal
component analysis showed that N2O emissions were mainly determined by the
distribution of nitrogen in the soil and were affected by the change in soil
total nitrogen content in the conventional treatment but N2O emissions were more
sensitive to the variation in soil inorganic nitrogen in the film mulching
treatment.
PMID- 29965225
TI - [Effects of Bamboo Biochar on Greenhouse Gas Emissions During the Municipal
Sludge Composting Process].
AB - Effect of adding bamboo biochar into the compost at different dosages on
greenhouse gas emissions was investigated by analyzing the dynamic
characteristics of the process of municipal sludge composting with four different
composts (S1:adding 2.5% bamboo biochar, S2:adding 5% bamboo biochar, S3:adding
10% bamboo biochar, CK:without bamboo biochar). The results showed that CH4
emissions mainly occurred during the heating period and the beginning of the
altithermal period, accounting for 99.01%-99.81% of the total emissions. When the
added bamboo biochar is less than 5%, CH4 emissions decrease with the increase in
the amount of bamboo biochar. If it is more than 5%, CH4 emissions will clearly
increase. CO2 emissions mainly occurred during the heating period and the
altithermal period, accounting for 75.65%-86.58% of the total emissions. Adding
bamboo biochar can reduce 3.37%-13.48% of the CO2 emissions but there is no
significant difference between the treatments (P>0.05). N2O emissions mainly
occurred during the heating period and the rotten period. Adding bamboo biochar
can reduce the emissions of N2O; the more the amount of bamboo biochar, the less
N2O emissions (P<0.05). The emission factors of CK, S1, S2, and S3 were 44.10,
37.57, 35.10, and 35.44 kg.t-1 of dry sludge, respectively. S1, S2, and S3 showed
14.81%-20.41% reduction in greenhouse gas emissions owing to the addition of
bamboo biochar, indicating that bamboo biochar can reduce the carbon emissions in
the process of sludge composting.
PMID- 29965226
TI - [Removal of Cd from Soil by Aspergillus fumigatus in a Semi-solid Culture].
AB - A method was proposed to remove Cd from contaminated soils by a semi-solid
culture containing Aspergillus fumigatus that have a strong resistance to Cd. The
removal efficiencies of Cd in different simulated Cd pollution levels were
studied and the changes in Cd adsorption and the enrichment in Aspergillus
fumigatus were measured. The results showed that Aspergillus fumigatus could
remove some Cd from the soil in the semi-solid culture system. When the
concentration of Cd was 10 mg.kg-1, the total removal rate of Cd was up to 31%.
Meanwhile, the dry weight of Aspergillus fumigatus and the pH of the system were
studied during the culture process. The results showed that the dry weight
decreased with the increase in culture time and Cd concentration, the maximum
decrease rate of dry weight was 64%. The removal efficiency was the best when the
pH was varied from 5.6 to 6.0. The changes in different extraction fractions for
Cd showed that the main fractions of Cd removed by Aspergillus fumigatus were the
acid-soluble fraction and the reducible fraction and the oxidizable fraction of
Cd remained essentially unchanged before and after the culturing. The proposed
method would provide valuable information for the remediation of heavy metal
contaminated soil by fungi.
PMID- 29965227
TI - [Removal of Chlortetracycline and Morphological Changes in Heavy Metals in Swine
Manure Using the Composting Process].
AB - The widespread use of antibiotics and heavy metals in livestock farms results in
large residues of antibiotics and heavy metals in the livestock manure.
Composting technology can biodegrade residual antibiotics and solidify heavy
metals. A pilot composting reactor was used to analyze the characteristics of
chlortetracycline (CTC) removal at different antibiotic concentrations[0 mg.kg-1
(CK), 10 mg.kg-1 (T1), and 50 mg.kg-1 (T2)]. Moreover, the morphological changes
in heavy metals during the composting process were analyzed. After composting, no
chlortetracycline was detected in the CK group and the antibiotics degradation
rates of T1 and T2 groups reached 96.31% and 97.32%, respectively. The
chlortetracycline degradation fits the pseudo-first-order kinetics model. Heavy
metals can be solidified during the composting; thus, the bioavailable state of
Cu and Zn (exchangeable state, reducible state) changed into the oxidation state
and residues with apparent passivation formed. The correlation analysis showed
that the removal of CTC showed strong positive correlations with the biological
available Cu and Zn.
PMID- 29965228
TI - [Remediation of Petroleum-Contaminated Soil Using a Bioaugmented Compost
Technique].
AB - Bioaugmented compost was created by inoculating petroleum-degrading bacteria into
mature compost. The petroleum hydrocarbon degradation efficiencies were
investigated by applying this enhanced compost to petroleum-contaminated soil
under low temperatures. The results showed that the degrading bacteria can be
enriched in the mature compost. After 30 d of remediation, the removal efficiency
of TPH, alkanes, and PAHs in the soil was 27.0%, 19.6%, and 10.0%, compared to
natural attenuation (CK), which was 4.5%, 9.5%, and 2.3%, respectively. In
response to remediation, the relative abundance of Proteobacteria and
Actinobacteria phyla decreased from 53.4% and 25.9% to 48.9% and 14.1%,
respectively, and Bacteroidetes phylum increased from 5.0% to 24.5%. At the genus
level, the relative abundance of Acinetobacter and Pseudomonas increased from
0.02% and 3.4% to 15.2% and 4.6%, respectively. The results indicated that the
bioaugmented compost may efficiently facilitate and speed up the bioremediation
of petroleum-contaminated soil under low-temperature conditions. Soil microbial
diversity and structure of microbial communities are sensitive to the
remediation.
PMID- 29965229
TI - [Effects of Microbial Diversity on Soil Carbon Mineralization].
AB - Soil microbial community plays an important role in ecosystem functions; however,
little is known about the importance of microbial diversity to the ecosystems. In
this study, serial dilution of soil suspension (10-1, 10-3, and 10-5) was
performed and inoculated into the sterilized soils that form the broadleaf mixed
forests in Pangquangou. The change in the carbon mineralization rate and the
pattern of the carbon source utilization were studied by titration, Biolog Eco,
and other experimental methods. The results show that after being incubated for
six weeks, carbon mineralization rate, the cumulative amount of carbon
mineralization, average well color development (AWCD), and diversity index
(Shannon, McIntosh, and richness index) of D1 were significantly higher than
those of the D5 treatment. The cumulative amount of carbon mineralization and
AWCD was strongly and inversely correlated with richness. Principal component
analysis and one-way ANOVA also indicated that the patterns of carbon source
utilization of microbially diverse soil were different. Therefore, the loss of
microbial diversity affects the carbon mineralization rate and the pattern of
carbon source utilization, leading to functional changes in terrestrial
ecosystems. In the management of forest soils, the effects of soil microbial
diversity on ecosystem functions should be considered.
PMID- 29965230
TI - [Ozone Deposition and Risk Assessment for a Winter Wheat Field:Partitioning
Between Stomatal and Non-stomatal Pathways].
AB - To better understand the ozone deposition and risk assessment over agroecosystems
based on the ozone flux indices, an eddy-covariance system was used for measuring
the ozone deposition continuously and dynamically in a winter wheat field. We
analyzed the variations in ozone concentration, total ozone flux, and stomatal
and non-stomatal flux. The relationships between stomatal/non-stomatal ozone
deposition velocity and the main meteorological factors were investigated.
Finally, the yield losses of winter wheat based on the ozone-dose index (AOT40)
and ozone flux index (DFs06) were calculated. Results showed that average daily
ozone concentration (cO3) was 32.9 nL.L-1. The daytime (08:00-18:00) and
nighttime total ozone flux (FO3) were -7.6 nmol.(m2.s)-1 and -3.1 nmol.(m2.s)-1,
respectively, and the mean diurnal FO3 was -5.1 nmol.(m2.s)-1. The mean daily
stomatal ozone flux (Fs) and non-stomatal ozone flux (Fns) ranged from 0 to -5.1
nmol.(m2.s)-1 and from -1.43 to -10.31 nmol.(m2.s)-1, respectively. The mean
diurnal Fs and Fns were -1.43 nmol.(m2.s)-1 and -3.66 nmol.(m2.s)-1. High solar
radiation (SR), high temperature (T), and moderate humidity were used to analyze
stomatal ozone deposition; high SR, moderate T, and high humidity were suitable
to analyze non-stomatal ozone deposition. The cumulative total ozone flux (DFO3),
cumulative stomatal ozone flux (DFs), and cumulative non-stomatal ozone flux
(DFns) were 31.58, 9.99, and 21.59 mmol.m-2 during the entire experimental
period, and DFs and DFns accounted for 32% and 68% of DFO3. The ranges of yield
loss in winter wheat were estimated at 11.58%-20.37% and 20%-23.56% using
different assessment models based on the ozone dose index AOT40 and ozone flux
index DFs06, respectively.
PMID- 29965231
TI - [Progress in the Studies of Precipitation Chemistry in Acid Rain Areas of
Southwest China].
AB - The precipitation data for nine sites in the acid rain area of southwest China
were analyzed. The data included pH and the concentrations of major ions (Cl-,
SO42-, NO3-, Ca2+, NH4+, Mg2+, K+, and Na+). SO42- and NO3- were the main anions,
whereas Ca2+ and NH4+ were the main cations in the precipitation. The
concentrations of acidic ions, alkaline ions, and total ions in this area were
significantly higher than those reported in southeast China, but much lower than
those in northern China. About 58% of the total precipitation has a pH value
ranging from 4.5 to 5.6. According to the correlation of acidic and alkaline ions
as well as the results of the neutralization factor, the rainwater in this area
has been neutralized. Ca2+ and NH4+ are the dominant neutralization substances in
rainwater. Comparisons of pH and the main ion components with other areas showed
that rainfall neutralization in this area was stronger than that in southeast
China but poorer than that in northern China. Calculation of enrichment factors
for rainwater components relative to soil and seawater indicated that Ca2+ and
Mg2+ mainly originated from terrestrial sources and SO42- and NO3- were mostly
attributed to the anthropogenic activities in this area. In addition,
approximately 99.7% of Ca2+ and 84.0% of Mg2+ were attributed to terrestrial
sources and were closely related to the widespread distribution of carbonate
rocks in the southwest of China.
PMID- 29965232
TI - [Emission Characteristics of Vehicles from National Roads and Provincial Roads in
China].
AB - In recent years, with the rapid increase in automobile volume, vehicle emissions
have become one of the major emission sources of urban air pollution in China. In
China, most of the national and provincial roads have been the channels that
connect different cities. Up until 2015, the length of national and provincial
roads have reached 1.85*105 km and 3.29*105km, respectively, accounting for 13%
of the mileage of all classified highways. Therefore, active research on vehicle
emissions from national and provincial roads between cities in China is of great
significance. Few studies have been conducted on air pollutant emissions from
intercity vehicles. In this study, emission characteristics of intercity vehicles
were investigated based on traffic monitoring data and the "calculation guide of
air pollutant emission for road vehicles". The results showed that the CO, NOx,
PM, and HC emissions accounted for 4.5%, 27.9%, 14.4%, and 7.7% of national
vehicle emissions, respectively. There were significant differences in emission
contributions among different types of intercity vehicles. Heavy trucks were
major contributors to NOx, PM10, and PM2.5 emissions and motorcycles contributed
most to CO and HC. Furthermore, there were significant differences in emission
contributions of vehicle types on different road types; the major contributor of
CO and HC emissions was small passenger cars on expressways. Motorcycles were the
main contributors to CO and HC emissions on ordinary roads.
PMID- 29965233
TI - [Impact of Gusty Northwesterly Winds on Biological Particles in Winter in
Beijing].
AB - Biological aerosol particles play a crucial role in cloud formation and
succession of ecosystems and have a large impact on human health. However, the
variations in the concentration, composition, and viability of biological
particles remain unclear. This study, conducted in January 2013 and January 2015
in Beijing, explores the influence of meteorological conditions on the variations
in the concentration and composition of biological particles. Concentrations of
biological particles were measured by an online optical detector, waveband
integrated bioaerosol sensor (WIBS-4A). The composition of bacterial communities
within biological particles was measured by 16S rDNA sequencing. The results
showed that the number concentration of biological particles ranged from 2 L-1 to
150 L-1 during winter. The wind could largely influence the concentration and
composition of biological particles. During gusty northwesterly winds, when wind
speed was above 4 m.s-1 and wind direction was from the northwest (~30 degrees ),
the concentration increased by one order of magnitude, and the composition of
bacterial communities sharply changed. After the passage of gusty winds, the
composition gradually changed back to its prior state.
PMID- 29965234
TI - [Characteristics of Particulate Matter and Carbonaceous Species in Ambient Air at
Different Air Quality Levels].
AB - This study describes the characteristics of particulate matter and carbonaceous
species at different air quality levels. The concentrations of PM10, PM2.5, PM1,
and carbonaceous species in PM2.5 were monitored on-line in Langfang City on
March 1-22, 2016. The PM10, PM2.5, and PM1 concentrations were 204.1 MUg.m-3,
107.9 MUg.m-3, and 87.8 MUg.m-3, respectively. Diurnal variations in particulate
matter concentrations showed a bimodal distribution. In general, the mass
concentrations of particulate matter and carbonaceous species (OC, EC, SOC, and
POC) and the ratios of PM1/PM10 and PM2.5/PM10 were lower on better air quality
periods. However, the mass concentration of PM10 was the highest on moderately
polluted times. The ratios of PM1/PM10 and PM2.5/PM10 reached minimum values on
moderately polluted times.The mass concentration of OC was slightly lower in
moderately polluted periods than slightly polluted times; it was significantly
lower in moderately polluted periods compared to severely polluted time periods.
Hourly concentrations of OC and EC were lower between the hours of 13:00 and
23:00 compared to slightly polluted and severely polluted periods. The proportion
of PM2.5 and PM1 decreased in moderately polluted time periods, consistent with
the corresponding primary pollutants. Besides, the value of OC/EC was larger than
2.0. The concentrations of SOC and POC estimated using the minimum OC/EC ratio
were 12.2 MUg.m-3 and 5.0 MUg.m-3, respectively.
PMID- 29965235
TI - [Distribution and Health Risk Assessment of Heavy Metals in Atmospheric
Particulate Matter and Dust].
AB - In order to study the concentration, distribution characteristics, and health
risk assessment of toxic heavy metals, Cu, Mn, Pb, Ti, V, Cd, Cr, Co, Mo, and Ni,
in atmospheric particulate matter (PM) and dust, the PM and dust samples were
collected in all four seasons in 2014 in Beijing using two high volume air
samplers (Echo Tecora Inc., Italy) and a dust tank, respectively. Selected metals
were quantified by ICP-MS. Annual average concentrations of PM2.5 and PM10 were
153.40 MUg.m-3 and 232.93 MUg.m-3, which were five and three times higher than
the Ambient Air Quality Standard values (GB 3095-2012), respectively. The average
PM2.5/PM10 was 0.74, implying that PM2.5 predominated the particulate matter
concentrations. The results of backward trajectory analysis suggested that
exogenous particles originated from the northwest, north-northeast, southeast,
and southeast-northwest during winter, spring, summer, and autumn, respectively.
The order of annual average concentrations of selected metals in PM2.5 and PM10
was Ti > Mn > Pb > Cu > Cr > Ni > V > Cd > Mo > Co. The sum of the concentrations
of Ti, Mn, Pb, Cu, and Cr accounted for 91.93% and 92.49% of the total
concentration of target metals in PM2.5 and PM10, respectively. The metal content
of dust followed the order of Ti > Mn > Pb > Cu > Ni > Cr > V > Co > Mo > Cd and
Ti (2561.48 MUg.g-1) accounted for 72.57% of the total metal content of dust. The
geo-accumulation index (Igeo) of Cd, Pb, Cu, and Ni were 4.03, 2.49, 1.33, and
0.43, which represented the states of heavily to extremely contaminated,
moderately to heavily contaminated, moderately contaminated and uncontaminated to
moderately contaminated, respectively, indicating that dust in the target area
included significant amounts of Cd, Pb, and Cu. The health risk assessment
suggested that non-carcinogenic and carcinogenic risks of selected metals in PM10
and dust were within safe limits, but their long-term impact cannot be ignored.
PMID- 29965236
TI - [Observational Study of Air Pollution Complex in Nanjing in June 2014].
AB - Studying the evolution of secondary inorganic aerosols, which are important
components of PM2.5, is crucial to improving our understanding about the air
pollution in big cities. This study investigates the evolution and factors of
secondary inorganic aerosols based on two pollution incidences in Nanjing in June
2014. A significant characteristic of air pollution complex with the coexistence
of higher concentrations of both PM2.5 and ozone is observed. In the earlier
stage of the pollution episode, ozone concentrations were high, which could
exceed 250, triggering a stronger oxidation in the atmosphere and a higher
production potential of nitric acid that leads to the quick production of
nitrate. In the later period of the pollution episode, relative humidity played
an essential role. An increase in relative humidity would result in a sharp
decrease in the theoretical product of the partial pressures of NH3 and HNO3,
especially when relative humidity exceeds the mutual deliquesce relative humidity
that makes it easier to form nitrate. The difference in the theoretical and
observational partial pressure product could characterize the evolution of
nitrate perfectly.
PMID- 29965237
TI - [Distribution Characteristics of Air Pollutants and Aerosol Chemical Components
Under Different Weather Conditions in Jiaxing].
AB - Distribution characteristics of air pollutants and aerosol chemical components
under different weather conditions were investigated in Jiaxing between May 1 and
31, 2015. The particulate matter (PM), gaseous pollutants, chemical components in
PM1.0, and aerosol number concentrations ranging from 10 nm to 10 MUm were
measured using the SHARP-5030 monitoring instrument, Thermo EMS system, Aerodyne
Aerosol Chemical Speciation Monitor (ACSM), and Wide-Range Particle Spectrometer
(WPS), respectively. The average concentrations of PM2.5, PM1.0, SO2, NO2, O3,
and CO were 52.8 MUg.m-3, 37.2 MUg.m-3, 10.3 MUg.m-3, 38.1 MUg.m-3, 92.1 MUg.m-3,
and 1.2 mg.m-3 during the observation period. The chemical components of OA, SO42
, NO3-, NH4+, and Cl-in PM1.0 had average concentrations of 2.18, 1.24, 0.87,
0.63, and 0.08 MUg.m-3, respectively. The aerosol number concentrations were
mainly centralized in Aitken mode (20-100 nm), with a value of 12411.2 cm-3. The
nuclei mode aerosols (10-20 nm) followed the number concentrations with 4946.6 cm
3. The concentration distributions and diurnal variations of PM and gaseous
pollutants, and the distributions of chemical components of PM1.0 varied under
different weather conditions. The concentrations of chemical components were
ranked in the order of OA > SO42- > NO3- > NH4+ > Cl- on rainy days and sunny
days, and in the order of OA > NO3- > SO42- > NH4+ > Cl- on new particle
formation (NPF) days. The OA and NO3- concentrations on NPF days were 1.61 and
1.42 times larger than those on sunny days, suggesting that the components of OA
and NO3- were the main substances influencing the NPF events. Additionally, the
diurnal variations of aerosols in different modes varied under different types of
weather conditions.
PMID- 29965238
TI - [Observations of Reactive Nitrogen and Sulfur Compounds During Haze Episodes
Using a Denuder-based System].
AB - Reactive nitrogen and sulfur compounds are chemically active in the atmosphere
and play an important role in secondary particle formation. Among them, sulfate,
nitrate, and ammonium (SNA) are important components of particulate matter (PM)
that account for approximately one-third of fine particles. The precursors of SNA
including HNO3, SO2, and NH3 are all involved in haze formation in China. To
date, the concurrent measurements of SNA and their precursors have been limited
to single sites and short terms because of the high cost of the instruments. This
study aimed to use DELTA (Denuder for Long-Term Atmospheric sampling) to
characterize the daily concentrations of reactive nitrogen and sulfur species
during haze episodes. The results showed that the background interface of NH4+,
NO3-, and SO42- in the denuder was minor and could be used to determine 24-48 h
concentrations of NH3, HNO3, SO2, NH4+, and NO3-. However, the SO42-
concentrations in the blank filter was so high that they could only be used for
sampling weekly or for longer periods of time. During the campaign between May 9
and June 7, 2016 in urban Beijing, the concentrations of NH3, HNO3, NH4+, and NO3
showed distinct daily variations at different wind directions, i.e., higher
values were observed during southerly winds and lower values during northerly
winds. The time series of these reactive nitrogen compounds coincided with that
of PM2.5, CO, SO2, and NO2, indicating the combustion of fossil fuels. The mean
concentrations of NH3, HNO3, NH4+, and NO3- were twice the concentrations during
clean days, further highlighting the effect of local emissions on the urban
environment. The ratios of HNO3/NO3- and NH3/NH4+ were 1.2 and 4.5, respectively,
without significant differences between hazy and clean days. The findings
demonstrated that both the reduced and oxidized nitrogen were preferred in
gaseous phase rather than particulate phase due to relatively high temperatures
during the transition season of spring/summer.
PMID- 29965240
TI - [Levels, Sources, and Health Risk Assessments of Heavy Metals in Indoor Dust in a
College in the Pearl River Delta].
AB - Thirty indoor dust samples were collected from staff and study areas in a college
in Foshan, and the As, Hg, Cd, Cu, Zn, Ni, Pb, and Cr contents were measured. The
Spearman correlation coefficient, principal component analysis, and US EPA health
risk assessment model were used to determine the sources and degree of pollution
and the health risks. The results showed that the levels of the eight heavy
metals were higher than the background values in Guangdong Province and the
reported values in other Chinese cities, excluding Hg. The levels of the eight
heavy metals were higher in the staff area than in the study area, but the
difference was not significant. The eight heavy metals were derived from similar
sources; Hg was mainly derived from outdoor anthropogenic sources, while the
others were mainly derived from indoor anthropogenic sources. The daily non
carcinogenic exposure dose was in the following order:ingestion > dermal exposure
> inhalation. Ingestion was the major pathway of heavy metal exposure from indoor
dust. Except for Cr, the non-carcinogenic hazard indexes of ingestion and dermal
exposure were taken from partial sample points > 1. All of the health risks were
lower than the average risk thresholds of the heavy metals, and would not cause
health risks to humans. Printers, copiers, instruments, and equipment were
important sources of indoor pollution and risk sources of heavy metals. Thus,
protective measures should be taken to reduce the risk of exposure.
PMID- 29965239
TI - [Analysis of Anthropogenic Reactive Nitrogen Emissions and Its Features on a
Prefecture-level City in Fujian Province].
AB - The impacts of reactive nitrogen (Nr) on the environment significantly increase
with population and rapid urbanization. In order to study gaseous Nr and Nr loads
to waterbodies at the provincial scale, we established anthropogenic emission
inventories in prefecture-level cities in Fujian Province and analyzed the
changes in Nr emissions for the years 2000, 2005, and 2010. The total Nr
emissions were calculated as 538.4, 587.0, and 620.0 Gg in those three years,
respectively. The emissions of Nr increased in nine prefecture-level cities
except in Zhangzhou. Among these nine cities, Putian is the fastest growing one.
The largest emitters were Zhangzhou and Quanzhou, while Ningde and Xiamen were
the smallest ones. Agricultural ecosystems and livestock were the main sources of
Nr emissions, both of them accounting for more than 90% of total anthropogenic Nr
emissions. Despite rapid growth, energy activities had a minor contribution to
total Nr emissions. The per area Nr emissions of each prefecture-level city were
highest in Xiamen in the southeast coastal area and lowest in Sanming located in
the northwest inland region in 2010. However, the patterns of GDP, population,
and emission intensities showed the opposite trends to per area Nr emissions,
lowest in Xiamen and highest in Nanping. We further discussed the significance of
Nr emissions reductions in different areas based on the analysis of the
characteristics of Nr emission sources in prefecture-level cities. The results
provide a scientific basis for reducing Nr emissions in Fujian Province and its
prefecture-level cities.
PMID- 29965241
TI - [Influence of Noble Metal and Promoter Capacity in CDPF on Particulate Matter
Emissions of Diesel Bus].
AB - This study investigates the influence of noble metal capacity and promoter
capacity in diesel oxidation catalysts (DOC) and catalyzed diesel particulate
filters (CDPF) on particulate matter (PM) emissions. Four types of exhaust
aftertreatments were applied to a diesel bus engine that meets the national III
emissions regulations. On-board tests were conducted respectively. PM emissions
from the engine were strongly influenced by noble metal capacity in DOC and CDPF,
especially at high speeds (the total number of particles increased by 70.8% when
the noble metal capacity decreased by 5 g.ft-3 at 60 km.h-1). The higher the
noble metal capacity was, the lower the PM emissions became, especially for PM in
nuclei mode. The lanthanide material contributed to reducing PM emissions
significantly. The content of precious metals could be reduced by 25% with proper
lanthanide material, while the treatment effect of exhaust particles was
guaranteed. In summary, aftertreatments are not sensitive to accelerating
conditions, but the purification efficiency is obviously different under
decontamination conditions.
PMID- 29965242
TI - [Spatial Distribution, Source and Ecological Risk Assessment of Heavy Metals in
the Coastal Sediments of Northern Dongying City].
AB - Concentrations of seven heavy metals in the coastal sediments of the northern
Dongying City were measured. The spatial distribution and sources of heavy metals
were discussed and the ecological risk was assessed using sediment quality
guidelines (SQGs) and the potential ecological risk index (PERI). The
concentration ranges of Hg, As, Pb, Cd, Cr, Cu, and Zn were calculated as 0.005
0.092, 3.44-10.41, 6.59-19.00, 0.50-1.10, 32.42-60.25, 1.72-23.78, and 31.13
69.96 mg.kg-1, respectively. Higher metal concentrations were observed at site
S10, which was close to the mouth of Tiaohe River and contained plenty of organic
matter, silt, and clay. Principal component analysis (PCA) indicated that As and
Pb in the sediments were derived from natural weathering processes, while other
metals were mainly attributed to anthropogenic sources, i.e., land-sourced
pollutants transported by runoff. Concentrations of As, Cd, Cr, and Cu at some
sampling sites exceeded the threshold effect level (TEL) stated in the SQGs
implying occasional harmful effects on biological life. PERI showed that the
sediments in this area generally had a medium risk, except sites S10, S3, and S9
posing a considerable risk, and that Cd and Hg were the major contributors to the
ecological risk. It is necessary to take effective measures to control heavy
metal fluxes from rivers around this area and to reduce the risk.
PMID- 29965243
TI - [Remote Sensing of Chlorophyll-a Concentrations in Lake Hongze Using Long Time
Series MERIS Observations].
AB - Chlorophyll-a (Chl-a) concentrations are usually measured as the proxy of
phytoplankton biomass and used to evaluate the trophic status of inland waters.
Based on 49 in situ samples taken from two measurement campaigns in Lake Hongze
in 2016, we evaluate the performance of five Chl-a estimation algorithms
(including the band ratio, three-band, FLH algorithm, MCI, and UMOC algorithms).
The results showed that the UMOC model was the most suitable model for the
estimation of Chl-a in Lake Hongze. The mean relative error (MRE) of UMOC was
32.30%, much lower than the band ratio algorithm (75.17%), three-band algorithm
(62.44%), FLH algorithm (45.87%), and MCI algorithm (56.95%). The best-performing
UMOC model was applied to the atmospherically corrected 689 MERIS images between
2002-2012 and long time series MERIS Chl-a concentration estimation products were
acquired. Between 2002 and 2012, the mean Chl-a concentration in Lake Hongze was
19.560 mg.m-3 with substantial spatial and temporal variability. Based on the
variability of monthly mean Chl-a concentrations in each pixel, the Lake Hongze
waterbody was divided into three water types, Region A, Region B, and Region C.
The annual mean Chl-a concentrations of Region B and Region C showed no
significant changes, while the concentrations in Region A increased markedly. The
analysis of the meteorological factors showed that the fluctuations of the annual
mean Chl-a concentrations in Region B and Region C were mainly affected by annual
precipitation, suggesting that the Chl-a concentrations of these two regions are
dominated by the intensity of the lake flow. The annual mean Chl-a concentrations
of Region A showed a strong negative correlation with the annual mean wind speed.
The descending trend of the annual wind speed may enhance the eutrophication
degree of this region, threatening the safety of the water quality of the South
North Water Transfer Project. The Chl-a concentrations showed a strong positive
correlation with the distance from the Huaihe Estuary in the wet season
suggesting that the Huaihe River has an obvious inhibitory effect on algal
biomass in Lake Hongze during this period.
PMID- 29965244
TI - [Analysis of Spatial Variability of Water Quality and Pollution Sources in Lihe
River Watershed, Taihu Lake Basin].
AB - The source of pollutants in the Tai Lake basin and the characteristics of
spatiotemporal variations were studied by conducting water quality monitoring in
the Lihe River watershed to the west of Tai Lake in 2014. The dynamic changes in
total phosphorus (TP), ammonia nitrogen (NH4+-N), and chemical oxygen demand
(COD) were studied in flood and non-flood seasons at five monitoring points from
upstream to downstream. The average concentrations of TP, NH4+-N, and COD were
0.176 mg.L-1, 1.075 mg.L-1, and 10.626 mg.L-1 respectively, and the water quality
was lower than the grade IV standard. From upstream to downstream, the
concentrations of TP and NH4+-N gradually increased. The water quality downstream
was poor, worse than the gradeVstandard; however, COD was low and met the grade
IV standard. During the non-flood season, the pollutant concentrations gradually
increased from upstream to downstream. There was no obvious trend in flood
season. Concentrations of pollutants gradually increased with the increase in the
area of inhabited land and decrease in the area of forest land. The population
density, livestock, and poultry production were significantly correlated with the
concentrations of pollutants in the river. The pollutants in the Lihe River
watershed mainly originated from human activities, and livestock and poultry
breeding activities.
PMID- 29965245
TI - [Distribution of Different Phosphorus Species in Water and Sediments from Gaocun
to Lijin Reaches of the Yellow River].
AB - The Yellow River is the second longest river in China, which plays a very
important role in the transportation of nutrients at the regional and even global
scale. Water and sediment samples were collected at five sites located at the
Gaocun to Lijin reaches along the Yellow River and the distribution
characteristics of different phosphorus species were analyzed. The concentration
of suspended particulate matter (SPM) in water ranged from 1.89 to 2.67 g.L-1
with an average of 2.26 g.L-1 in May and from 0.43 to 1.79 g.L-1 with an average
of 1.21 g.L-1 in September. It almost had the same variation rule as the water
flux, which reflects the influence of water flux on SPM transportation. The
concentration of total phosphorus (TP) in water ranged from 0.05 to 2.31 mg.L-1
in May and from 0.03 to 0.1 mg.L-1 in September. Particulate phosphorus (PP) was
the dominant TP species in both months, and TP and PP were significantly
correlated (P<0.01), which implied that phosphorus loss in soil from Gaocun to
Lijin reaches is still serious. Water runoff was positively correlated with TP
and PP (P<0.05), but negatively correlated with total dissolved phosphorus (TDP)
and dissolved inorganic phosphorus (DIP) (P<0.05, P<0.01, respectively).
Increasing water runoff obviously increased the dilution of TDP and DIP. The
concentration of SPM was negatively correlated with DIP (P<0.01), the adsorption
of SPM on phosphorus was mainly the adsorption of DIP. The permanganate index in
water was higher in fall suggesting more serious organic pollution and it was
positively correlated with DIP (P<0.01). The phosphorus content in sediments was
quite low in both months; the total phosphorus (TP) content in sediments ranged
from 284.23 to 569.58 mg.kg-1 in May and from 287.97 to 355.39 mg.kg-1 in
September. Calcium-bound phosphate (Ca-P) was the dominant species of inorganic
phosphorus (IP). The labile organic phosphorus (L-OP) content was significantly
correlated with runoff, SPM concentration, and permanganate index
(P<0.01,P<0.05,P<0.01, respectively). The organic phosphorus (OP) content was
significantly higher at the Lijin site in May, likely caused by the rainfall
runoff from the mining area around Lijin. The energy-based production activities
from the Gaocun to Lijin reaches should also be further investigated.
PMID- 29965246
TI - [Characterization of Phosphorus Fractions in the Soil of Water-Level-Fluctuation
Zone and Unflooded Bankside in Pengxi River, Three Gorges Reservoir].
AB - The concentrations of phosphorus fractions in the soils of the water-level
fluctuating zone (WLFZ) of Pengxi River in the Three Gorges Reservoir were
analyzed. The total phosphorus (TP), inorganic phosphorus (IP), and organic
phosphorus (OP) were studied using the standard measurement and test (SMT)
procedure. The average TP concentration was 575.29 mg.kg-1 and the average OP
concentration was 91.23 mg.kg-1 in the soils of WLFZ. The fractions of phosphorus
were analyzed by the Hedley method. In the soils of WLFZ, the relative abundance
of WA-Pi (weakly adsorbed inorganic phosphorus), PA-Pi(potential active inorganic
phosphorus), and Fe/Al-Pi(Fe/Al-bound inorganic phosphorus) accounted for 11.61%
of the extractable Pi, lower than that in the unflooded bankside soils. The
relative abundance of WA-Po (weakly adsorbed organic phosphorus) and PA-Po
(potential active organic phosphorus) accounted for 22.28% of the extractable Po
and the Fe/Al-Po (Fe/Al-bound organic phosphorus) accounted for 66.30%. In
addition, the Po content of the soils of WLFZ was lower than that of the
unflooded bankside soils and the difference in the Fe/Al-Po content in both soil
types was the highest. WA-Pt and PA-Pt were significantly correlated with TP in
the soils of WLFZ, which indicated that the active phosphorus content was mainly
affected by TP. There was no statistical correlation between different fractions
of phosphorus, suggesting different sources of phosphorus fractions. The Fe/Al-Pt
content was significantly correlated with OM, implying that the OM content may
affect the Fe/Al-Pt content. Therefore, under flood conditions, the potential
impacts of phosphorus in the soils of WLFZ on overlying water should not be
neglected.
PMID- 29965247
TI - [Distribution of n-alkanes from Lake Wanghu Sediments in Relation to
Environmental Changes].
AB - Concentrations and distribution of n-alkanes (n-C14 to n-C33) in Lake Wanghu
sediment core were analyzed to investigate the environmental changes in the lake
during the past~100 years. Relatively higher concentrations of mid-and long-chain
n-alkanes with a strong odd-over-even carbon number predominance indicated
organic matter contributions dominated by aquatic macrophytes and terrestrial
plants. The lower values of 2n-C31/(n-C27+n-C29) highlighted a type of landscape
dominated by woody plants. The environmental changes that have been happening
over the past 100 years in Lake Wanghu can be divided into three stages, based on
the organic matter sources inferred from the changes in n-alkane parameters in
the sediments. Before the 1950s, higher values of terrigenous/aquatic ratio (TAR)
and high-/low-molecular weight n-alkanes (H/L) indicated vascular, plant-derived
sediments deposited during a low-nutrient, clear-water phase with frequent water
exchange between the lake and the Yangtze River. Between the 1950s and 1980s,
decrease in values of H/L and TAR, and increase in the proportion of mid-and
short-chain n-alkanes indicated a shift towards mid-and shorter-chain components
likely associated with the increasing contribution of macrophytes and algae.
Lower 2n-C17/(n-C23+n-C25) values indicated a relatively low algal abundance. In
that stage, the lake trophic state increased slightly with the decreasing
influence of the Yangtze River flow. After the 1980s,H/L and TAR values increased
and then decreased, total n-alkane concentrations and 2n-C17/(n-C23+n-C25)
increased significantly, especially after 2000s, suggesting the main contributor
to high organic matter input most likely shifted to algae because of the
eutrophication caused by anthropogenic activities.
PMID- 29965248
TI - [Hydrological Performance Assessment of Permeable Parking Lots in High Water
Areas].
AB - In order to evaluate the hydrological performance of permeable pavements in
mitigating the surface runoff, four pilot-scale permeable pavement units were
constructed in Shanghai and compared with impervious pavements. Three of the
permeable facilities with waterproof liners included a pervious concrete pavement
(facility I), permeable interlocking concrete pavement using cement stabilized
macadam as the base course (facility II) and permeable interlocking concrete
pavement using macadam as the base course (facility III). The other two
facilities were a conventional permeable interlocking concrete pavement without a
liner (facility IV) and an impervious concrete pavement control (facility 0). V
notch flow meters, data loggers, and a rainfall meter were mounted to monitor the
hydrological data. A double-ring infiltrometer was applied to evaluate the
infiltration rate of the pavements. During the one-year experiment, the surface
runoff and the underdrain discharge flow rate of the four pilot-scale facilities
were continuously monitored in actual rainfall and the total volume reduction,
peak flow reduction, and peak concentrating time of different facilities were
investigated. The results showed that the surface steady infiltration rates of
permeable interlocking concrete pavements were less than those of the pervious
concrete, and the surface steady infiltration rates of the two types of surface
layers decreased after one year of usage. The surface runoff reduction of the
four facilities showed no significant differences. The water volume reduction
rate of the three types of facilities was weak. The annual total volume reduction
rates were 24.2%, 28.5%, and 28.4%, and the controlled rainfall amounts were 5.2
mm, 7.8 mm, and 7.8 mm. The peak flow reduction rate and the time to the peak
flow of facility I were smaller than those of facility II and facility III. The
peak flow reduction rate and the time to the peak flow of the three facilities
showed significant negative correlation with rainfall intensity.
PMID- 29965249
TI - [Analysis of the Characteristics of Groundwater Quality in a Typical Vegetable
Field, Northern China].
AB - This study explores the impact of facility farming on the origin and composition
of groundwater and on the distribution characteristics of inorganic salts, heavy
metals, and dissolved organic matter in groundwater in a typical greenhouse
vegetable planting area in North China plains. The methods used include
conventional analysis, UV-Visible, and fluorescence spectroscopy combined with
parallel factor analysis, principle components analysis, and two-dimensional (2D)
hetero-spectral correlation spectra techniques. The results showed that the
hydrochemistry type of groundwater in the facility vegetable field was Cl-SO4,
the nitrogen content was higher than the National Groundwater V Class Quality
Standard (GB/T14848-93), and the heavy metal content was lower than the National
Drinking Water Standard (GB5749-2006). The nitrification process was blocked due
to a strongly reducing atmosphere and shallow depth in groundwater, which caused
high concentrations of NH4+-N. Part of the toxic sulfur-containing metal content
increased after the application of inorganic fertilizers. The sources of
dissolved organic matter in groundwater were similar; the organic manure
components which leach into groundwater were recently produced by microbial
metabolism. The main components of dissolved organic matter were small-molecule
biodegradable protein-like substances and the fulvic-like content binding to
them. The fulvic-like content that bound to protein-like content in vegetable
planting groundwater was stable, while the protein-like content was greatly
influenced by the cultivation process of the organic manure application. In the
process of vegetable planting, organic manure should be applied scientifically
and the supervision of the planting area is crucial.
PMID- 29965250
TI - [Composition, Evolution, and Complexation of Dissolved Organic Matter with Heavy
Metals in Landfills].
AB - Samples of wastes and leachates were collected from a landfill site and a
leachate treatment plant[i.e., equalization basin, anaerobic zone, oxidation
ditch, and membrane bioreactor (MBR) section]. Dissolved organic matter (DOM) was
extracted from the wastes and leachates, and its composition, evolution, and
complexation characteristics with heavy metals were studied using UV-Visible and
fluorescence spectroscopy combined with1H nuclear magnetic resonance. The
aliphatic compounds were found to be the main substances in DOM in the fresh
landfill wastes (<5 a), and the relative content of aromatics and substituent
groups, i.e., carbonyl, hydroxyl, and carboxyl functional groups, decreased
during the initial process. On the other hand, carbohydrates and organic amines
were observed to be the main substances in DOM obtained from the intermediate and
old landfill wastes (>5 a), and the relative content of aromatics and substituent
groups (carbonyl, hydroxyl, and carboxyl functional groups) increased
persistently during the process of organic matter humification. The aliphatics,
carbohydrates, and organic amines all existed in DOM from the equalization basin
Carbohydrates and aromatic compounds increased rapidly after the anaerobic,
aerobiotic, and membrane treatment. However, low molecular weight organic matter
and alkyl chain substances decreased during the leachate treatment process and
the side chain of the aliphatics was shortened despite the increase in its
content. The distribution of zinc in the wastes and leachates was influenced by
the complexation with the nitrogen-and oxygen-containing functional groups, whose
effect on other metals was not obvious.
PMID- 29965251
TI - [Correlations Between Substrate Structure and Microbial Community in Subsurface
Flow Constructed Wetlands].
AB - To identify the microbial factors that cause the differences in the purification
performance of constructed wetlands with different substrate structures, the
relationship between the substrate structure and the microbial community
composition in horizontal subsurface flow constructed wetlands (HSSFCWs) was
studied by high throughput sequencing. The results revealed that the purification
performance of a six-layer constructed wetland (CW6), of which the permeability
coefficient gradually increased from the surface layer to the bottom layer, was
the highest among the three constructed wetland systems. The average
concentrations of COD, TN, NO3--N, and NH4+-N in the effluent were 39, 11, 0.35,
and 4 mg.L-1, respectively. The monolayer structure constructed wetland (CW1) had
the worst purifying efficiency, with average effluent concentrations of 95, 21,
0.60 and 12 mg.L-1 for COD, TN, NO3--N, and NH4+-N, respectively. The results of
the high-throughput sequencing showed that the number of microbial OTUs in
multilayer structure wetlands was slightly lower than that in the monolayer
structure wetland, but the relative abundance of the dominant phylum
Proteobacteria and the nitrifying and denitrifying bacteria in the genus was
significantly higher than the monolayer structure wetland. The results of PCA and
heatmap indicated that there were significant differences in the spatial
distribution of microbes in the genus of Proteobacteria in CW3 and CW6, which
facilitated the degradation of pollutants. No significant differences were found
in the community structure of CW1.
PMID- 29965252
TI - [Impact of Talc Ore Mining on Periphyton Community Structure and Water
Environment].
AB - In order to explore the impact of Talc ore mining on aquatic ecosystems,
periphyton communities and environmental factors from control portion, impacted
portion and recovery portion separately were investigated and analyzed. Samples
were collected from upstream Tanghe River (an important tributary of Tazi River)
in November 2015, April 2016, and July 2016. Mann-Whitney U test was applied to
compare the differences in environmental factors and periphyton community
structures among three portions. Spearman correlation analysis, canonical
correspondence analysis, and t-value biplot analysis were used to determine the
relationship between the environmental factors and periphyton community
structures. In the control and recovery portions, mass concentrations of
magnesium (Mg), selenium (Se), arsenic (As), iron (Fe), molybdenum (Mo),
bicarbonate ion (HCO3-), nitrate ion (NO3-), power of hydrogen (pH) and electric
conductivity (EC), were the highest, and in the impacted portion, mass
concentrations of potassium(K), sodium (Na), strontium (Sr), barium (Ba), silicon
dioxide (SiO2), and dissolved oxygen (DO) were the lowest. The mass
concentrations of Mg, Mo, As, EC, and HCO3- were significantly different (P<0.05)
among the three portions. In control and recovery portions, the periphyton
density, species richness, diatom siltation index, and relative abundance of
Achnanthes sp. were the highest, while in the impacted portion, the percentage of
handle diatom, the relative abundance of Surirella sp., and relative abundance of
Navicula sp. were the lowest. Species richness of periphyton was significantly
different (P<0.05) among the three portions. In summary, Mg, EC, and HCO3- from
Talc Ore mining had significant impacts on periphyton assemblage structure.
PMID- 29965254
TI - [Removal of Algal Organic Matter and Control of Disinfection By-products by
Powder Activated Carbon].
AB - The removal efficiencies of algal organic matter (AOM) and typical nitrogenous
and non-nitrogenous disinfection by-products (DBPs) through adsorption with
powder activated carbon (PAC) were investigated. Three-dimensional fluorescence
spectroscopy confirmed that PAC adsorption changed the composition of AOM. PAC
adsorption showed high removal efficiency for humus-like substances in AOM, but
limited removal efficiency for aromatic protein-like substances. When the dosage
of PAC was 20 mg.L-1 and the adsorption time ranged from 10 to 30 min, the
removal rates of 3.30 mg.L-1 dissolved organic carbon were 20.7%-31.9% for
intracellular organic matter (IOM) and 12.6%-19.0% for extracellular organic
matter (EOM). The highest removal rates of trihalomethanes by PAC in the
chlorination of IOM and EOM were 26.6% and 35.8%, respectively. The highest
removal rates of haloacetonitriles were 49.6% and 53.6% in the chlorination of
IOM and EOM. The removal of dibromoacetonitrile precursors by PAC was
significant. In summary, the PAC had a higher efficiency in reducing the
generation of DBPs in EOM chlorination than in IOM chlorination.
PMID- 29965253
TI - [Physiological Characteristics and Nitrogen and Phosphorus Uptake of Myriophyllum
aquaticum Under High Ammonium Conditions].
AB - Ammonium nitrogen (NH4+-N) at high concentrations is toxic to plants. In order to
explore the NH4+-N tolerance of Myriophyllum aquaticum (M. aquaticum) and its
ability of nitrogen (N) and phosphorus (P) uptake, this study used a nutrient
solution with three NH4+-N levels (70, 210, 420 mg.L-1) to incubate M. aquaticum
for 21 d. The characteristics of plant physiology and N and P uptake of M.
aquaticum were measured. At NH4+-N of 70 mg.L-1, M. aquaticum grew healthily, and
shoot height and biomass linearly increased with the increase incubation time.
Relative shoot height and biomass of M. aquaticum were 40.56 cm and 17.82 g.hole
1 on day 21, respectively. Compared to the control with 70 mg.L-1 ammonium,
malondialdehyde (MDA) content of M. aquaticum was significantly increased;
chlorophyll and soluble sugar contents were also high at NH4+-N of 210 mg.L-1. M.
aquaticum suffered from the NH4+-N stress. However, the stress of 210 mg.L-1 NH4+
N did not affect its normal growth and there was no significant difference in the
relative growth rate of the shoot height and biomass compared with the control.
At NH4+-N of 420 mg.L-1, MDA contents of M. aquaticum doubled and the shoot
height and biomass growth rate were only 27.4% and 17.9% of those for 70 mg.L-1
NH4+-N, indicating that M. aquaticum was subjected to serious stress that caused
unhealthy growth or even death. At three NH4+-N levels, the ranges of N and P
content of M. aquaticum were 30.7-53.4 mg.g-1 and 3.8-7.7 mg.g-1, respectively,
which indicated that M. aquaticum had a high uptake capacity of N and P. M.
aquaticum is an ideal wetland plant that has a good application prospect for
constructed wetlands in biological treatment of high-ammonia wastewater.
PMID- 29965255
TI - [Preparation and Pb2+ Electrosorption Characteristics of Graphene Hydrogels
Electrode].
AB - Electrosorption has the advantage of high adsorption capacity and electrode
regeneration in the removal of heavy metal ions in water. In this study, graphene
hydrogels (GS) were prepared by hydrothermal reduction of graphene oxide (GO)
suspensions and the electrode was obtained via compression of GS. Various
electrochemical properties of GS were tested. The kinetics and thermodynamics of
the electrosorption of Pb2+ on GS electrode and GS electrode reusability were
investigated. The results showed excellent capacitive behavior (200.4 F.g-1 at 1
A.g-1) of GS. The electrosorption performance of GS indicated that high voltage
was favored for the removal of Pb2+ and the highest removal efficiency reached
96.4% when the voltage value was -1.2 V. The electrosorption capacity for Pb2+
removal was found to be 461.20 mg.g-1, which was twice as high as the saturated
adsorption capacity of GS. The GS electrode could regenerate after
electrosorption when the voltage value was+1.2 V and the removal efficiency of
Pb2+ was still maintained above 95% after electrosorption-desorption for 15
cycles.
PMID- 29965256
TI - [Influence of Current Densities on Mineralization of Indole by BDD Electrode].
AB - Electrochemical oxidation by boron-doped diamond (BDD) electrode is an effective
method of degrading refractory organics. Compared with TOC detection, the amount
of gas escape can more effectively and intuitively reflect the mineralization and
the removal extent. In this study, indole is chosen as a typical pollutant and
the detection of its removal rate was compared at current densities of 10, 20,
and 30 mA.cm-2. Meanwhile, the degradation mechanism was analyzed based on the
changes in the carbon and nitrogen forms and conservation status. As a result,
BDD electrodes displayed a higher removal efficiency to indole, which can
completely be removed after 8 h, 5 h, and 4 h with current densities of 10, 20
and 30 mA.cm-2, respectively. Changes in TOC removal and CO2 generation were both
increased with increasing the current densities, suggesting that the
mineralization extent was in accordance with current densities. Furthermore, the
escaped CO2, combined with TOC and TIC constituted a conservative carbon system.
The byproduct isatin was stable and accumulated at 4-5 h, as TOC, TON, and CO2
generation was unchanged at this stage. Finally, the XPS analysis suggested the
adsorption by-products such as isatin and benzoquinone on the BDD surface, which
can further be removed by increasing the electrolysis time. This study
demonstrated the mineralization process of indole based on the escaped gas
detection and the changes in the carbon and nitrogen forms, which will increase
the understanding of the electrolysis process.
PMID- 29965257
TI - [Mechanism of Photochemical Degradation of MC-LR by Pyrite].
AB - Pyrite was used as catalyst to degrade Microcystin-LR (MC-LR) at pH 6.8 under
visible light irradiation (lambda>420 nm). X-ray diffraction (XRD) and scanning
electron microscope (SEM) characterization showed that pyrite had the layered
structure. The ion state of pyrite before and after the reaction was identified
using X-Ray Photoelectron Spectroscopy (XPS), confirming the conversion process
of Fe(II) to Fe(III) on the sulfur defect sites. Electron Spin Resonance (ESR)
test showed that pyrite photochemical reaction produced hydroxyl radical (.OH).
The results of high performance liquid chromatography (HPLC) and liquid
chromatograph-mass spectrometer (LC-MS) showed that visible light irradiation
could effectively activate pyrite to degrade MC-LR. The degradation rate of MC-LR
reached 100% after 10 hours and the mineralization rate reached 60% after 20
hours. The two reaction pathways of photochemical oxidation of MC-LR by pyrite
were discussed.
PMID- 29965258
TI - [Enhanced Treatment of Printing and Dyeing Wastewater Using H2O2-Biochemical
Method].
AB - The traditional biochemical treatment of printing and dyeing wastewater has
limited efficiency. This study investigated whether H2O2 could strengthen the
biological ability of the hydrolytic acidification/biological contact oxidation
process (A/O), which effectively treats the printing and dyeing wastewater. After
biofilm formation and the biochemical system startup and operation by H2O2, the
system was successfully started and steadily operated when H2O2was added into
reactor A with the H2O2 voluve fraction of 3 mL.L-1, doses of 100.0 mL, the flow
velocity of 0.67 mL.min-1, and dosing frequency of once a day. The experimental
results showed that the average removal efficiencies of COD, ammonia nitrogen,
PVA, and color of printing and dyeing wastewater were 89.8%, 96.7%, 87.4%, and
92.1%, respectively. The microorganism community structures of reactor A and
reactor O in this system were analyzed by high-throughput sequencing of 16S rDNA
amplicon. The results demonstrated that the three dominant microbial strains in
reactor A were Proteobacteria, Bacteroidetes, and Verrucomicrobia, and in reactor
O were Planctomycetes, Proteobacteria, and Acidobacteria.
PMID- 29965259
TI - [Effects of Influent C/N Ratios on Denitrifying Phosphorus Removal Performance
Based on ABR-MBR Combined Process].
AB - An ABR-MBR integrated reactor based on a combination of the anaerobic baffled
reactor (ABR) with the microbial phase separation and membrane bioreactor (MBR)
with high-effect entrapment was constructed and the circulation and interactivity
of the combined process were examined by adding nitrate recycling and sludge
reflux. By increasing the influent COD to adjust the COD/TN ratio, the influence
of the mechanism on the denitrifying phosphorus removal performance under the
condition of continuous-flow was investigated. The results showed that the
average effluent concentration of soluble phosphorus under different influent C/N
conditions were 0.22, 0.34, 0.39, 0.42, and 2.45 mg.L-1 and the low influent C/N
ratio was beneficial to phosphate removal. When the influent C/N was 4.8-6.0, the
average removal rates of COD, TN, and soluble PO43--P were more than 87%, 76%,
and 93%. In addition, when the influent C/N ratio was 3.6-6.0, the removal of TN
was proportional to the anoxic phosphorus uptake of ABR and conducive to the
removal of TN after increasing the influent COD concentration. Higher C/N ratios
of the influent improved the removal of TN at this stage. Finally, the C/N ratio
of 6 was suggested to achieve the simultaneous removal of nitrogen and
phosphorus.
PMID- 29965260
TI - [Start-up of a High Performance Nitrosation Reactor Through Continuous Growth of
Aerobic Granular Sludge].
AB - In order to examine the continuous growth capacity of the nitrosation granular
sludge (NGS), the sludge was inoculated to start up the columnar sequencing batch
reactor (SBR). During 130 d, the concentration of mixed liquor suspended solids
(MLSS) in SBR increased from 0.1 g.L-1 to 11.8 g.L-1, corresponding to the
nitrite-nitrogen accumulation rate of 0.4-4.9 kg.(m3.d)-1, promoted by a higher
ammonia-nitrogen loading rate (NLR) from 0.74 kg.(m3.d)-1 to 6.66 kg.(m3.d)-1in
the influent. Because of the obvious increase in small granules (size<200 MUm),
the mean average diameter of NGS decreased significantly at NLR<4.44 kg.(m3.d)-1.
At higher NLR values, the growth of the mean average diameter of NGS could be
fitted well using a modified logistic model. The specific growth rate of the k
value was 0.0229 d-1. In addition, the combined inhibition of nitrite oxidizing
bacteria (NOB) was expected at relatively high concentrations of both free
ammonia (FA) and free nitrite acid (FNA); thus, the nitrite accumulation ratio
(NAR) in the effluent was always higher than 80%. These results provide a
feasible approach to start up a high-performance NGS reactor at the industrial
scale.
PMID- 29965261
TI - [Activated Sludge Mineralization and Solutions in the Process of Zero-Valent Iron
Autotrophic Denitrification].
AB - We studied the inoculation of activated sludge from domestic sewage treatment
plants. The reaction of reducing nitrate by zero-valent iron was started in the
up-flow anaerobic reactor. After 52 d of operation, a nitrogen removal rate of
29.3 g.(m3.d)-1 was achieved. Ferric iron and iron oxide coated on the sludge
formed in the operation process caused the mineralization and slowly decreased
the sludge activity. The methods of the "supplement and replacement of the sludge
in the reactor" and "changing the reflux mode of the reactor" were applied. Using
the method of the supplement and replacement of the sludge in the reactor, by
discharging a part of the sludge in the reactor and adding the extra dosage from
the anaerobic denitrifying sludge for the treatment of wastewater, after 22 d of
operation, the conversion rate of nitrate-nitrogen was 33.0 g.(m3.d)-1 and the
concentration of nitrite-nitrogen was 16.50 mg.L-1. The effluent average
concentration of ammonia-nitrogen decreased from 12.38 mg.L-1 to 3.58 mg.L-1 and
the nitrogen removal rate was recovered from 9.9 g.(m3.d)-1to 15.0 g.(m3.d)-1.
The biological reaction weakened the chemical reduction of nitrate by zero-valent
iron. Using the method of changing the reflux mode of the reactor, the reflux
tank was arranged outside the reaction column using hydraulic circulation. The
increase in the erosion of the upper layer of the sedimentation tank would bring
out ferric iron and iron oxide with the outflow water and they would be deposited
in the reflux tank. The corresponding ferric iron of transformation of nitrate
settled in the external reflux tank was 58% at the ascending velocity of 3.49 m.h
1. The nitrate-nitrogen conversion rate was 34.3 g.(m3.d)-1, the effluent
concentration of nitrite-nitrogen was 0.22 mg.L-1, and ammonia-nitrogen was 0.75
mg.L-1. Ammonia and nitrite did not extensively accumulate. The nitrogen removal
rate was 33.4 g.(m3.d)-1, which solved the problem of the mineralized sludge in
the long-term reactor operation. In summary, the method of reforming the reflux
mode of the reactor performed better than the method of the supplement and
replacement of sludge in the reactor.
PMID- 29965262
TI - [Analysis of Respirogram Characteristics of Filamentous Bulking Caused by Low
Dissolved Oxygen].
AB - The current research on filamentous bulking focuses on the effluent quality and
the settling properties but the reports on the microbial physiology under
filamentous bulking conditions are seldom. In this study, the variations in the
respirogram of microorganisms and affinity coefficient during filamentous bulking
were explored in a sequence batch reactor. Low dissolved oxygen, regarded as the
typical reason for filamentous bulking, was applied as the stimulation method.
The results showed that microorganisms entered the physiological adaptation stage
in the early period of low DO. The following properties were observed in the
system:1 a sudden increase in the endogenous specific oxygen uptake rate (SOURe)
of activated sludge, 2 an abrupt decrease in the specific oxygen uptake rate
(SOURn) of autotrophic bacteria, 3 a rapid increase after a slight decline in the
specific oxygen uptake rate (SOURc) of heterotrophic bacteria and a sudden
increase in the oxygen affinity coefficient (KO). However, maintaining the low DO
levels would deteriorate the effluent quality and sedimentation properties, but
the SOURn and SOURc could recover to higher levels after a while and the COD
affinity coefficient (KS) and KO would decrease gradually. In low DO conditions,
a sufficient hydraulic retention time will benefit the effluent quality from a
theoretical point of view. Moreover, microorganisms could adapt to low DO
conditions, which verifies the feasibility of "low oxygen aeration theory" from
the respiration and kinetic parameters. The results from this study provide a
theoretical support for energy savings of sewage treatment plant operations.
PMID- 29965263
TI - [Aerobic Degradation and Microbial Community Succession of Coking Wastewater with
Municipal Sludge].
AB - Coking wastewater is a typical industrial wastewater with high toxicity. Its
treatment with biological processes is often challenging because it contains
constituents inhibiting microbial activity. To study the inhibitory effect and
possible acclimation of microbes in coking wastewater treatment, municipal sludge
was inoculated into coking wastewater. Time-dependent concentrations of COD,
phenol, ammonia nitrogen, and thiocyanide in coking wastewater were analyzed. The
microbial community structure was investigated by the Illumina high-throughput
sequencing technology during inoculation. The results showed that COD began to
decrease after 16 h and 97.1% of phenol disappeared after 40 h. Thiocyanide began
to degrade at 72 h and was undetectable after 96 h. Accordingly, the
concentration of ammonia increased as the thiocyanide concentrations decreased.
High-throughput pyrosequencing analysis showed that the microbial community
structure and species richness varied at different culture stages. In the stage
of phenol degradation, the abundance of Acinetobacter and Pseudomonas increased
rapidly; the species richness was 13.04% of the community at 48 h. In the stage
of thiocyanate degradation, Sphingobacterium,Brevundimonas,Lysobacter, and
Chryseobacterium were the dominant bacteria and were 16.13% of the community at
96 h. At 144 h, Fluviicola,Stenotrophomonas, and Thiobacillus became the dominant
species and were 22.45% of the community abundance. The results showed that
municipal sludge can rapidly overcome the toxicity of coking wastewater because
the pollutants are degraded rapidly. The microbial community structure changed as
wastewater components were degraded. Environmental factors and the competition
among bacteria played a key role in microbial community succession.
PMID- 29965264
TI - [Rapid Culture, Microbial Community Structure, and Diversity of High-Efficiency
Denitrifying Bacteria].
AB - High-efficiency denitrifying bacteria can improve wastewater treatment
efficiency. In order to rapidly culture high-efficiency denitrifying bacteria,
batch trials were conducted at different carbon sources (No. 1 and No. 2
fermented liquid) and NO3--N concentration gradients (30 mg.L-1-150 mg.L-1-300
mg.L-1). The results showed that No. 2 fermented liquid could finish high
efficiency denitrifying bacteria[300 mg.(L.h)-1] cultivation in 11 d, which is 17
d before No.1 fermented liquid could. At the same time, high-efficiency
denitrifying bacteria could effectively remove ammonia-nitrogen and total
phosphorus, and maximum removal rates were 34.43 mg.(L.h)-1 and 2.98 mg.(L.h)-1,
respectively. Furthermore, high-throughput sequencing was employed to
characterize and compare the community structure and diversity. The species
abundance and diversity were reduced but the category and proportion of
denitrifying bacteria were increased. In addition, bacteria composition and
quantity changed after cultivation and Thauera and Pseudomonas were the dominant
contributors to the effective removal of nitrate in the SBR(sequencing batch
reactor). Denitrifying phosphorus accumulating bacteria (Rhodocyclaceae and
Pseudomonadaceae) and heterotrophic nitrifying bacteria
(Pseudomonas,Alcaligenes,Bacillus, and Comamonas) proved the capacity of the
system to remove ammonia-nitrogen and total phosphorus.
PMID- 29965265
TI - [Abundance of Cell-associated and Cell-free Antibiotic Resistance Genes in Two
Wastewater Treatment Systems].
AB - For revealing the characteristics of antibiotic resistance genes (ARGs) in
wastewater treatment systems, real-time PCR was adopted to investigate the
variation of abundances of cell-associated ARGs and cell-free ARGs, in a
municipal wastewater treatment system (M for short) and a coking wastewater
treatment system (C for short). In system M, the absolute abundances of the cell
associated ARGs, sul II,tetC,blaPSE-1, and ermB, were much higher than those of
the cell-free fractions in the influent. The biological treatment process did not
enrich antibiotic resistance bacteria (ARBs) and membrane filtration of the MBR
effectively reduced both cell-associated and cell-free DNA in water. The total
ARGs removal was 2.54-4.95 logs. In system C, the biological treatment process
enriched the sul II -carried ARBs; however, the relative and absolute abundances
of cell-free sul II were decreased. The succeeding process, coagulation-sand
filtration, decreased the absolute abundance of cell-associated sul II, but
increased the absolute abundance of cell-free sul II in water. The proportion of
cell-free sul II in total sul II gene increased from 0.05% in the biological
treatment effluent to 1.33% in the sand filtration effluent and further increased
to 9.31% after the effluent was kept at 25C and at dark for five days. The ratio
of cell-free ARGs to total ARGs increased with deep removal of ARBs and lysis of
residual cells. The risk of ARG proliferation by cell-free DNA in the effluent
needs further evaluation.
PMID- 29965266
TI - [Effect of Biochar on CH4 and N2O Emissions from Lou Soil].
AB - In order to investigate the effect of biochar on CH4 and N2O emissions from Lou
soil, field plot experiments of winter wheat were conducted with five levels of
biochar addition (0, 20, 40, 60, and 80 t.hm-2). The fluxes of CH4 and N2O, wheat
production, soil organic carbon, soil water content, and temperature of each soil
layer were measured. The results showed that the fluxes of CH4 and N2O changed
significantly in different growth periods of winter wheat. Compared with the
control, the cumulative CH4 uptake under the biochar amendment increased by
12.88%-71.61%. When the biochar addition was >= 40 t.hm-2, the cumulative CH4
uptake was significantly higher and the highest uptake was at the level of 40
t.hm-2. Biochar amendment had no significant effect on cumulative N2O emissions
and the global warming potential (GDP). The greenhouse gas intensity (GHGI)
decreased by 13.24%-22.14%. The wheat yield increased by 1.72%-32.19% after
biochar addition. When the applied biochar level was >= 40 t.hm-2, the wheat
yield increments were significantly higher. The biochar addition of 40 t.hm-2 was
the optimal level for increasing the wheat yield. The soil organic carbon and
water content under biochar amendment increased by 1.42-2.69 times and 7.08%
11.96%, respectively. The results suggested that Lou soil was the sink of
atmospheric CH4 and the emission source of N2O during the winter wheat growth
period, and the biochar level of 40 t.hm-2 was the optimal addition amount.
PMID- 29965268
TI - [Influence of Calcium Carbonate and Biochar Addition on Soil Nitrogen Retention
in Acidified Vegetable Soil].
AB - In Taihu Lake region, more and more paddy fields are being converted to vegetable
fields, which cause serious soil acidification and decreased soil nitrogen
retention. In this study, calcium carbonate and biochar were used as
acidification amendments to test their ability on soil acidification remediation
and soil nitrogen retention improvement. Calcium carbonate and biochar addition
rates were determined by pH buffering curves. An incubation experiment with and
without nitrogen fertilization and multi-leaching simulation tests were
conducted. The soil nitrogen mineralization rate, dynamics of the nitrogen
content in soils and leachates, and soil pH were measured. The results showed
that 3.92*10-2 mol.kg-1 calcium carbonate and 27.73 g.kg-1 biochar should be
added into the tested acidified vegetable soil to recover the original pH value.
Without nitrogen fertilization, the addition of calcium carbonate increased the
soil nitrogen mineralization rate by 37% but had no significant effect on mineral
nitrogen content. However, biochar addition significantly improved the soil
nitrogen mineralization rate by 35%-44% and nitrate content by 42%-58%. Nitrogen
leaching loss was cut down by 42%-57% in biochar addition treatment because of
the lower leachate volume and nitrogen concentration, while calcium carbonate
addition increased nitrogen leaching loss by 12%-76% because of the higher
leachate nitrogen concentration. After leaching, the soil pH decreased for all
the treatments. The soil pH change was the lowest for calcium carbonate addition
treatment under no nitrogen fertilization and the lowest for biochar addition
treatment under nitrogen fertilization. This result suggests that calcium
carbonate is more applicable for seriously acidified soils which are fallowed and
biochar is more suitable for the intensified vegetable fields because it can
improve the soil nitrogen retention and soil pH, and reduce the nitrogen leaching
loss.
PMID- 29965267
TI - [Spatial Variability of C-to-N Ratio of Farmland Soil in Jiangxi Province].
AB - Spatial variability of soil carbon-to-nitrogen ratio (C/N) at the provincial
scale was analyzed using ordinary kriging methods. The effects of the factors
influencing C/N were quantified by regression analysis based on 16,582 points of
surface soil samples (0-20 cm) collected during the project of soil-test-based
formulated fertilization in Jiangxi Province in 2012. The results showed that
soil C/N ranged from 2.98 to 52.67, with an average of 11.72. The coefficient of
variation was 25.17%, suggesting moderate variability. The nugget-to-sill ratio
was 88.44%, meaning that the stochastic factors played a more important role in
the spatial variability of soil C/N between the structural and stochastic
factors. The spatial distribution of soil C/N was relatively smooth and the high
value areas were mainly distributed in Pengze County-Jiujiang City, Shangli
County-Pingxiang City, and Lean County-Fuzhou City. The terrain factors, farmland
use type, parent material, soil type, and the level of nitrogen fertilizer had
significant impacts on the spatial variability of soil C/N (P<0.05), but the
degree of influence was different for each factor. Soil C/N indicated a
significant positive Pearson's correlation with elevation and the slope of slope
(P<0.05). The terrain factors explained 0.3% of the spatial variability of soil
C/N and the farmland-use could explain 1.4%. The explanatory power of soil
groups, subgroups, and soil family were 2.7%, 3.6%, and 5.5% respectively. The
level of nitrogen fertilizer could explain 33.4% of the spatial variability of
soil C/N, which showed that the amount of nitrogen fertilizer was the main factor
that controls the spatial distribution of soil C/N.
PMID- 29965269
TI - [Comparison of Soil Hydraulic Characteristics Under the Conditions of Long-term
Land Preparation and Natural Slope in Longtan Catchment of the Loess Hilly
Region].
AB - Soil moisture plays a crucial role in maintaining the health and sustainability
of dryland ecosystems. Terracing and other similar land preparations can reshape
the natural slope and change underlying surface into different micro-landforms,
which are significant for rainwater harvesting, erosion control, and vegetation
promotion in arid regions. In this study, the Longtan Watershed in Dingxi region
was selected as the study area. Based on in situ experiments, soil sampling
analysis, and modeling simulation, the effects of land preparation and artificial
vegetation (Fish-scale pit/Adverse grade tableland-Platycladus orientalis) on
soil moisture characteristics curves and soil moisture constants were
quantitatively analyzed. 1The land preparations could effectively improve the
soil moisture content in the study catchment of Loess Plateau. Compared with
natural slope, soil water content of land preparations increased by 1.883%(volume
fraction) on average and fish-scale pit method and adverse grade tableland method
enhanced the soil moisture by 29.69% and 15.55%, respectively. 2 Compared with
the natural slope, fish-scale pit and adverse grade tableland could significantly
improve the soil hydraulic properties. After carrying out the land preparations,
saturated soil water content and soil properties such as field capacity increased
by 4.24%-11.40%, suggesting that land preparations can improve soil moisture and
water supply ability. 3 Surface soil moisture characteristics were better than
those of the underlying soil layers after land preparations. Compared with the
natural slope, fish-scale pit and adverse grade tableland's shallow soil layer (0
20 cm) increased the moisture by 38.75% and 23.84%, respectively, whereas in the
deep layer (60-80 cm) the increment of moisture were only 3.34% and 3.85%,
respectively. This research provides scientific basis for vegetation restoration
and land improvement in fragile semi-arid ecosystems.
PMID- 29965270
TI - [Effects of Organic Carbon Content on the Residue and Migration of Polycyclic
Aromatic Hydrocarbons in Soil Profiles].
AB - The effects of total organic carbon content (TOC) on the migration of polycyclic
aromatic hydrocarbons (PAHs) in the soil were investigated. This study analyzed
the vertical properties of the concentrations and distributions of PAHs and TOC
at various soil profiles from functionally different environmental regions
including nature reserves, ploughs, orchards, farmlands, metropolitan areas, and
industrial parks. The vertical migration properties of PAHs in soils were
examined by conducting leaching experiments in soil columns. The concentrations
of PAHs varied from region to region and showed strong, positive correlations
with TOC in the same region. Furthermore, based on the leaching experiments, the
transport abilities of PAHs were significantly influenced by TOC, although they
could all be transported to the deep layers by TOC in soil columns. The downward
migration of PAHs decreased with the increase in TOC and vice versa. The
properties of the composition and structure of PAHs also had an obvious influence
on their residues and migration in soil profiles at the same TOC conditions. In
addition, the transport of PAHs was related to the amount of leaching water, the
leaching time, and the additional PAHs.
PMID- 29965271
TI - [Major Factors Influencing the Cd Content and Seasonal Dynamics in Different Land
Cover Soils in a Typical Acid Rain Region].
AB - Understanding the seasonal variations in active heavy metal components and
sensitive impact factors is of importance for the ecological risk reduction
during the agricultural production processes. Paddy fields, vegetable lands, and
hilly forests were selected as three main land cover types to assess the seasonal
characteristics of Cd bioavailability and reveal how or to what extent it was
affected by the physiochemical parameters of soils, under different land-use
types in a typical Cd-contaminated watershed in the middle and lower reaches of
Xiangjiang River. One-year in situ monitoring results showed that natural
rainfall pH in winter and spring was lower than in summer and autumn in the study
region. The total Cd content of paddy soils was significantly higher than that of
the vegetable soil, while the hilly forest soil showed the lowest total Cd value.
Similar seasonal variations in total Cd content were found in three soil types
with slightly lower summer and autumn concentrations than spring and winter
values, but no obvious correlation was detected between the total and the
available Cd components. The paddy soil available Cd concentration during the 5-9
month crop growth season was significantly lower than the other months of the
year, while vegetable cultivation and hilly forest soils showed the opposite
trend. Eh was the key factor that had a positive influence on the Cd activity in
paddy soil. Soil TOC concentration was negatively correlated with soil activity
in vegetable soil. TOC, water soluble organic carbon, showed a significant
positive correlation with Cd effectiveness. The results provide scientific
references for Cd contamination control and safe agricultural production.
PMID- 29965272
TI - [Application Potential and Assessment of Metallurgical Contaminated Soil After
Remediation in Tongguan of Shaanxi].
AB - There has been a growing interest in soil replacement and in-situ stabilization
techniques in recent years. Many techniques in the remediation of contaminated
soils have been proven to be effective methods. In this study, lime and calcium
phosphate were added to immobilize the heavy metals in contaminated soils. The
long-term application potential of these techniques were evaluated by taking the
demonstration project of the soil remediation in Tongguan of Shaanxi as the case
study.The status of heavy metal contamination in the study area resulted from
artisanal gold mining was discussed. The strategies of remediation and the
evaluation of the remediation results including the safety of agricultural
practices were also studied. The results showed that soil was seriously
contaminated in the study area with Cd, Pb, and Hg, and the residue mining waste
was the main source. The potential ecological risk index ranged from 668 to
10969, suggesting that all the samples posed a very strong ecological hazard.
Based on the pollution status, the soil replacement method and stabilization
method were applied. Acceptable remediation results were obtained with lower
total metal content (except Cd) and decreased heavy metal availability. However,
the metal content of agricultural products was higher than the permissible value
according to GB 2762-2012, which means that agricultural practices pose risks on
remediated soils. Soil replacement and stabilization would be practical
techniques for heavy metal polluted soil remediation. However, a consecutive
investigation should be conducted for the assurance of food safety.
PMID- 29965273
TI - [Effects and Mechanisms of In-situ Cement Solidification/Stabilization on a Pb-,
Zn-, and Cd-Contaminated Site at Baiyin, China].
AB - In order to evaluate the effects and mechanism of in-situ cement
solidification/stabilization (S/S) on heavy metal contaminated soils, leaching
tests, speciation analysis, and microscopic analysis were conducted after cement
treatment of a Pb, Zn, and Cd contaminated site in Baiyin, China. The leaching
test results showed that cement could effectively stabilize Cd and Zn, which
could reduce 99.5%-100% and 96.6%-98.8% of H2SO4-HNO3 extractable Cd and Zn,
respectively. However, the leaching concentration of Pb was 2.6-5.8 times higher
than that before 5% cement treatment. After adding 8% cement, H2SO4-HNO3
extractable Cd and Zn were reduced by 99.6%-100% and 94.4%-97.9% respectively.
Similarly, the leaching concentration of Pb was 1.9-12.5 times higher than that
before 8% cement treatment. The results of sequential extraction test proposed by
the European Community Bureau of Reference (BCR) showed that cement could
transform acid extractable Cd and Zn to residual form and transform reducible
fractions of Pb to oxidizable and residual form, increasing the stability of
heavy metals in soil. The microscopic analysis results showed that Pb2+, Zn2+,
and Cd2+ could participate in the process of cement hydration and form silicate
minerals and hydroxides. In conclusion, cement could be an effective S/S agent to
remediate heavy metal contaminated soils, and site characteristics and
environmental conditions should also be considered during the construction
process.
PMID- 29965274
TI - [Concentrations and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons
(PAHs) in Soils and Vegetables influenced by Facility Cultivation].
AB - The concentrations, sources, and health risks of 16 United States Environmental
Protcction Agency(USEPA) priority polycyclic aromatic hydrocarbons (PAHs) in
vegetables (leafy lettuce, amaranth, water spinach, and Shanghai green), in soils
inside and outside the vegetable greenhouse, and in wet deposition were
investigated by conducting an experiment on facility cultivation. The results
showed that the average concentrations of total PAHs in vegetables and soils were
99.27 ng.g-1and 128.01 ng.g-1 in the greenhouse, and 109.11 ng.g-1 and 173.07
ng.g-1 out of the greenhouse. The concentrations of PAHs in the greenhouse were
lower than those outside and the high ring-PAHs were lower than the low ring-PAHs
both inside and outside. The PAH concentrations in suspended particular matter in
dissolved phases of wet deposition were 2986.49 ng.g-1 and 61.9 ng.L-1,
respectively. The low rings were easily enriched by the vegetables based on the
shoot concentration factors. PAHs in soils and vegetables mainly originated from
oil emissions and grass, wood, and coal combustion, while those in suspended
particular matter in wet deposition were from petrogenic sources and the
combustion of grass, wood, and coal. Petroleum combustion emissions were the main
sources of PAHs in dissolved phases. We used the model of incremental lifetime
cancer risks to evaluate the health risk of eating these vegetables. There was a
potential risk of cancer for both children and adults for all vegetables except
amaranth. The carcinogenic risk of vegetables outside the greenhouse was higher
than the risk inside. Amaranth had a low carcinogenic risk with the value of
incremental lifetime cancer risk lower than 10-6, while the risk of Shanghai
green ranged between 10-4 and 10-6.
PMID- 29965275
TI - [Effects of Arbuscular Mycorrhizal Fungi on the Growth and Uptake of La and Pb by
Maize Grown in La and Pb-Contaminated Soil].
AB - A greenhouse pot experiment was conducted to investigate the effects of
arbuscular mycorrhizal (AM) fungi Claroideoglomus etunicatum (CE) and Rhizophagus
intraradices (RI) on AM colonization rate, biomass, nutrient uptake, C:N:P
stoichiometry, and the uptake and transport of lanthanum (La) and lead (Pb) by
maize (Zea mays L.) grown in La-and Pb-contaminated soils (combined La-Pb
concentrations of 50, 200, and 800 mg.kg-1). The aim was to provide a scientific
basis for the remediation of soils contaminated by rare earth elements and heavy
metals. The results indicated that symbiotic associations were successfully
established between the two isolates and maize, and the average AM colonization
rate ranged from 26.7% to 95.8%. The increasing concentrations of La and Pb in
soils significantly decreased the mycorrhizal colonization rate, biomass, and
mineral nutrition concentrations of the maize, and significantly increased C:P
and N:P ratios and the concentrations of La and Pb in shoots and roots of maize.
The shoot and root dry weights of maize were significantly increased by 17.8%
158.9% with two AM fungi inoculations, while the P concentration of shoots and
roots of the maize were significantly increased by 24.5%-153.8%. Inoculation with
two AM fungi decreased the C:P and N:P ratios, consistent with the growth rate
hypothesis. With AM fungi inoculation in three types of La-Pb co-contaminated
soils, root Pb concentrations of the maize significantly increased by 51.3%
67.7%; shoot Pb concentrations of the maize significantly decreased by 16.0%
67.7%; and the transport rate of Pb from root to shoot of the maize decreased by
31.5%-54.7%. Meanwhile, inoculation with AM fungi significantly increased the
shoot La concentrations in the maize grown in soils mildly contaminated with La
Pb, while it significantly decreased shoot La concentrations, increased root La
concentrations of maize, and inhibited the transport of La from root to shoot of
the maize grown in soils moderately contaminated with La-Pb, but had no
significant effect in severely contaminated soils. The results showed that AM
fungi had the potential to promote phytoremediation of soils contaminated with
rare earth elements and heavy metals, with potential applications to revegetate
such contaminated soil ecosystems.
PMID- 29965276
TI - [Effects of Straw Incorporation on Cadmium Accumulation and Subcellular
Distribution in Rice].
AB - Cadmium (Cd) is classified as a Group-1 human carcinogen and rice consumption
constitutes a major source of dietary intake of Cd for populations whose staple
food is rice. Straw incorporation is widely performed in Cd-contaminated paddy
fields, which may significantly affect the bioavailability of Cd in soil and the
distribution of Cd in rice plants, consequently altering Cd accumulation in rice
grains. In this study, both pot and field trials were conducted to investigate
the effects of different amounts of straw incorporation (0.0%, 1.0%, 2.5%, and
5.0%) on Cd sub-cellular distribution in rice plants and Cd accumulation in rice
grains. The results showed that Cd was mainly sequestered in cell wall,
accounting for 86%-95% and 30%-51% of total cadmium in root and shoot cells,
respectively. In shoot cells, about 35%-61% of Cd was distributed in cellular
soluble fractions. When rice straw was incorporated at 1.0% and 2.5% levels, Cd
sequestration in the cell wall significantly increased and Cd translocation from
roots to shoots significantly decreased. However, when rice straw was
incorporated at the 5% level, Cd sequestration in root cell walls significantly
decreased and Cd translocation from roots to shoots significantly increased at
the tillering stage. At the filling stage, 5% rice straw incorporation still
significantly increased Cd sequestration in root cell walls and Cd translocation
from roots to shoots did not significantly change. The rice straw and rape straw
used for the field trail contained high concentrations of Cd (0.49 and 0.67 mg.kg
1, respectively). Rape straw incorporation alone or together with lime did not
significantly affect Cd accumulation in brown rice or rice straw. Rice straw
incorporation alone did not significantly affect Cd accumulation in brown rice or
rice straw, while incorporation with lime significantly decreased Cd accumulation
in both brown rice and rice straw. Biochar application can also significantly
reduce Cd accumulation in rice and when biochar was added together with lime, the
reduction in Cd accumulation in rice was more significant. Therefore, at Cd
contaminated paddy fields, rice straw or rape straw is not suggested to be
returned directly; incorporation with lime would be better for reducing Cd
accumulation in rice grains. The results of this study will provide theoretical
and practical guidance for the safe production of rice and for straw recycling at
Cd-polluted paddy fields.
PMID- 29965277
TI - [Redox Transformation of Arsenic and Antimony in Soils Mediated by Pantoea sp.
IMH].
AB - Soil contamination with co-existing arsenic (As) and antimony (Sb) has become a
serious environmental problem worldwide. Microorganisms play a dominant role in
the redox transformation and mobilization of As and Sb. As and Sb belong to the
same family; they are alike in nature and have related microbial oxidation
reduction mechanisms. However, limited knowledge is available about the impact of
As-reducing bacteria on the fate of As and Sb in their co-existing soils. The
purpose of this study was to explore the redox transformation and release of As
and Sb in the presence of an arsC carrier, Pantoea sp. IMH, which has high As(V)
reducing capability. In addition to the IMH incubation system, the dead cell
system and abiotic control experiments were conducted. The results showed that
the IMH incubation reduced all soluble As(V) (72.7 MUg.L-1) to As(III) form,
whereas soluble Sb(V) (364.8 MUg.L-1) was not reduced, indicating that the As (V)
reducing pathway mediated by arsC genesis was not able to reduce Sb(V). The
amounts of total As (506.8 MUg.L-1) and total Sb (821.1 MUg.L-1) in the dead cell
system were approximately four times higher than in the living cell system
(As=155.2 MUg.L-1; Sb=364.8 MUg.L-1) and the abiotic control (As=57.6 MUg.L-1;
Sb=271.1 MUg.L-1) because of the biomolecules released from the dead cells which
enhanced the release of As and Sb. The correlation analysis of dissolved As and
Sb showed that the release of total As and Sb was correlated (P<0.05) in three
systems. Our study shed new light on the impact of bacteria on the fate of As and
Sb in soils.
PMID- 29965278
TI - [Adsorption Characteristics of Biochar on Heavy Metals (Pb and Zn) in Soil].
AB - Three types of biochars, poplar branch biochar (PBC), water hyacinth biochar
(WHC), and corn straw biochar (CSC), were prepared in a fixed-bed pyrolyzer at
different pyrolysis temperatures (300-700C). The effects of biochar species,
pyrolysis temperature, and biochar addition on adsorption characteristics of
typical heavy metals (HMs) such as Pb and Zn in vegetable soil (collected from a
lead-zinc-silver mining area, Nanjing, China) were investigated. The adsorption
mechanism of biochar on HMs was discussed based on the analyses of pore
structure, XRD, and FTIR of biochars. WHC biochar showed the best adsorption
ability at the same experimental conditions with adsorption efficiencies on Zn
and Pb of 21.83% and 44.57%, respectively. The relative adsorption capacities of
Zn and Pb were 227.65 MUg.g-1 and 363.76 MUg.g-1 at the pyrolysis temperature of
500C and biochar addition of 5%. The adsorption efficiency of biochar on HMs in
soil increased gradually with increasing pyrolysis temperature. WHC biochars
prepared at 500C and 700C had similar adsorption capacities on Zn and Pb in soil
indicating that the moderate pyrolysis may be a good choice for WHC with better
physicochemical properties. Increasing the amount of WHC addition benefits the
adsorption efficiency of HMs in soil, but does not increase the adsorption
capacity. The adsorption efficiency of Pb in soil reaches 93.93% by adding 10% of
WHC into the soil sample. The combined analyses based on the physicochemical
properties of biochar and the results of soil HMs adsorption experiments suggest
that ion exchange and complexation are prevailing mechanisms of the remediation
of HM-contaminated soil by WHC biochars.
PMID- 29965279
TI - [Characteristics of Enteromorpha prolifera Biochars and Their Adsorption
Performance and Mechanisms for Cr(VI)].
AB - This study aims to understand the recycling process of Enteromorpha prolifera by
using the slow pyrolysis technology to prepare biochars under different
temperatures and by characterizing the physicochemical properties of biochars.
The results showed that a relatively high level pyrolysis of Enteromorpha
prolifera could be reached when the temperature was up to 400C. The yield rate
and the ash content of biochars were negatively correlated with the pyrolysis
temperature, while the carbon content was positively correlated. The specific
surface area of Enteromorpha prolifera biochars was in the range of 44.54-317.82
m2.g-1. The biochar surface was in the shape of a honeycomb and rich in oxygen
containing functional groups, such as hydroxyl (-OH) and carboxyl (-COOH) groups.
The adsorption experiments revealed that the adsorption of Cr(VI) onto
Enteromorpha prolifera biochars followed the pseudo-second-order kinetics
equation and Langmuir isotherm, indicating that the adsorption process was
controlled by the fast reaction process and governed by monomolecular and
chemical adsorption. The optimal pH for Cr(VI) adsorption onto Enteromorpha
prolifera biochars was 2 and their adsorption capabilities were in the order of
BC400 > BC700 > BC600 > BC500 > BC300 (the adsorption capacity of BC400 was 4.79
mg.g-1). The adsorption mechanism included the electrostatic interactions between
biochar and anions (HCrO-4 and Cr2O2-7) and the complexation of oxygen-containing
functional groups.
PMID- 29965280
TI - [External Phosphorus Adsorption and Immobility with the Addition of Ignited Water
Purification Sludge].
AB - The cumulative adsorption of external phosphorus (P) by water purification sludge
after ignition under different addition methods (mix and cover) was investigated
along with the adsorption isotherm and the release of internal P after external P
adsorption. The cumulative adsorption of external P was 11.496 mg (mix) and
11.042 mg (cover) and these values were higher than those in the control (7.219
mg). The maximum sorption capacity (Smax) increased under the mix and cover and
the former (7.795 mg.g-1) was higher than the latter (6.807 mg.g-1). However, the
zero equilibrium P concentration (EPC0) in the mix was 0.83 mg.L-1, higher that
in the cover (0.64 mg.L-1). The result suggests that the internal P was easily
released in the mix method, compared to the cover method. Under anaerobic
conditions, the release of the internal P was 0.93 mg in the mix, lower than that
in the cover (1.49 mg) and in the control (7.76 mg). In addition, the specific
release rate in the cover method was 0.00614 (mean), higher than that (0.00396)
in the mix method. Noticeably, these data were lower than those in the control,
indicating that the retention of P under the mix method was higher, compared to
the cover and the control and it is challenging to evaluate the P retention with
EPC0.
PMID- 29965281
TI - [Preparation of Adsorption Ceramsite Derived from Sludge Biochar].
AB - Adsorption ceramsite (SKC) was prepared with biochar (BC) derived from municipal
sludge and kaolin (KL) based on the optimized processing parameters to adsorb
ciprofloxacin (CIP) in aqueous solutions. The CIP adsorption mechanism of SKC was
investigated by adsorption kinetics and isotherm adsorption models, combined with
the analysis of microstructure, pore structure, phase composition, and zeta
potential. Furthermore, the heavy metal leaching toxicity was assessed using the
toxicity characteristic leaching procedure (TCLP) method. The results showed that
SKC, with 60% BC and 40% KL calcining at 1,050C for 5 min, showed an outstanding
removal efficiency of CIP (65.34%). The pseudo-second-order equation agreed with
the adsorption behavior and the Freundlich model described the adsorption process
well. The adsorption process was a multilayer adsorption controlled by physical
and chemical reactions. The leaching concentration of heavy metals, trapped by
the mineral phases in SKC was much lower than that in BC, indicating low
ecotoxicological risk. SKC possessed the ability to adsorb CIP with its developed
porosity and characteristic mineralogical phases, including silicon aluminum
oxide and iron oxide. This work provides a low-cost recyclable sorbing material
to remove high concentration CIP from wastewater and offers a new idea for the
large-scale safe use of BC.
PMID- 29965282
TI - [Construction of Graphitic Carbon Nitride-Bismuth Oxyiodide Layered
Heterostructures and Their Photocatalytic Antibacterial Performance].
AB - The thin layered graphitic carbon nitride (g-C3N4) was prepared by the thermal
polymerization process with urea as the precursor. The layered heterostructure of
graphitic carbon nitride-bismuth oxyiodide (g-C3N4/BiOI) was constructed by the
in-situ synthetization of bismuth oxyiodide (BiOI) on the surface of the thin
layered g-C3N4. The morphology, specific surface area, crystal structure,
molecular structure, light absorption properties, and surface properties were
characterized by TEM, BET, XRD, FT-IR, UV-Vis DRS, and XPS, respectively. The
disinfection performance of the synthesized catalysts under visible light
irradiation was investigated. The antibacterial mechanism of g-C3N4/BiOI in the
photocatalytic process was further revealed by the capture of sacrificial agents.
The results indicate that the prepared sample has a layered heterojunction
structure with a specific surface area of 63 m2.g-1 and its light absorption side
can obtain 600 nm. The results of the photocatalytic activity test indicate that
g-C3N4/BiOI can kill bacteria within 4 h, which is significantly higher than that
of g-C3N4 and BiOI. The main active species of g-C3N4/BiOI in the photocatalytic
process can be attributed to the photogenerated holes.
PMID- 29965283
TI - [Transport Loss Estimation of Fine Particulate Matter in Sampling Tube Based on
Numerical Computation].
AB - In-situ measurement of PM2.5 physical and chemical properties is a substantial
approach for the mechanism investigation of PM2.5 pollution. Minimizing PM2.5
transport loss in sampling tube is essential for ensuring the accuracy of the
measurement result. In order to estimate the integrated PM2.5 transport
efficiency in sampling tube and optimize tube designs, the effects of different
tube factors (length, bore size and bend number) on the PM2.5 transport were
analyzed based on numerical computation. The results showed that PM2.5 mass
concentration transport efficiency of vertical tube with flow rate at 20.0 L.min
1, bore size at 4 mm, length at 1.0 m was 89.6%. However, the transport
efficiency increased to 98.3% when the bore size increased to 14 mm. PM2.5 mass
concentration transport efficiency of horizontal tube with flow rate at 1.0 L.min
1, bore size at 4 mm, length at 10.0 m was 86.7%, and increased to 99.2% with
length at 0.5 m. Low transport efficiency of 85.2% for PM2.5 mass concentration
was estimated in bend with flow rate at 20.0 L.min-1, bore size at 4 mm,
curvature angle at 90 degrees . Laminar flow of air in tube through keeping the
ratio of flow rate (L.min-1) and bore size (mm) below 1.4 was beneficial to
decrease the PM2.5 transport loss. For the target of PM2.5 transport efficiency
higher than 97%, it was advised to use vertical sampling tubes with length less
than 6.0 m for the flow rates of 2.5, 5.0, 10.0 L.min-1 and bore size larger than
12 mm for the flow rates of 16.7 or 20.0 L.min-1. For horizontal sampling tubes,
tube length was decided by the ratio of flow rate and bore size. Meanwhile, it
was suggested to decrease the amount of the bends in tube of turbulent flow.
PMID- 29965284
TI - [Sources Analysis of Heavy Metal Aerosol Particles in North Suburb of Nanjing].
AB - Heavy metal aerosol particles were first measured with Single Particle Aerosol
Mass Spectrometry (SPAMS) in north suburb of Nanjing from January to December,
2013. Using the ART-2a neural network algorithm, we studied the chemical
characteristics of aerosol particles and found that the main sources of heavy
metal aerosols in Nanjing were industrial emissions, biomass burning, traffic
emissions, fuel combustion and dust, accounting for 35.7%, 34.45%, 13.6%, 11.03%
and 4.07% respectively. Pb, Cd and Cr-containing aerosols mainly came from
industrial emissions. Cu, Co and Hg-containing aerosols mainly came from biomass
burning. V, Zn and Ba-containing aerosols mainly came from traffic emissions. As
and Ni-containing aerosols mainly came from fuel combustion.
PMID- 29965285
TI - [Distribution Characteristics of Water Soluble Ions Under Different Weather
Conditions During the Youth Olympic Games in Nanjing].
AB - To study the variation characteristics of water soluble ions during youth Olympic
Games, PM2.5 and water soluble ions were observed by using the beta dust
instrument, Anderson 9th sampler and IC type ion chromatography analyzer from
August 6 to September 4, 2014. The observations were divided into three types of
weather, sunny, rainy and cloudy. The average concentrations of PM2.5 under
different weather conditions were sunny > cloudy > rainy days. The concentrations
of water soluble ions in PM1.1, PM1.1-2.1 and PM2.1-10 were also sunny > cloudy >
rainy days, and the obliterate of fine particles by precipitation process was
more obvious. The spectra of Ca2+ and Mg2+ were bimodal. The scavenging effects
of SO42- and NH4+ in range of 0.65-1.1 MUm were stronger. The ratio of NO3-/SO42-
under different weather conditions was less than 1, and the ratio of NO3-/SO42-
in rainy and cloudy days was higher than that in sunny days. The values of SOR
and NOR in the three kinds of weather conditions were more than 0.1, SO2 and NO2
had different degrees of transformation, there was more secondary pollutant in
the atmosphere.
PMID- 29965286
TI - [Seasonal Variation and Source Analysis of the Water-soluble Inorganic Ions in
Fine Particulate Matter in Suzhou].
AB - A total of 87 daily PM2.5 samples were collected in the urban area of Suzhou city
during 2015, representing spring, summer, autumn, winter, respectively. Mass
concentration of PM2.5 was analyzed gravimetrically. Water-soluble inorganic
ions, including F-, Cl-, NO3-, SO42-, Na+, NH4+, K+, Mg2+and Ca2+, were
determined by ion chromatography. The average mass concentration of PM2.5 was
(74.26+/-38.01) MUg.m-3. The seasonal variations of PM2.5 concentrations
decreased in the order of winter > spring > autumn > summer. The average total
mass concentrations of 9 ions was (43.95+/-23.60) MUg.m-3, and the order of
concentration of ions was NO3- > SO42- > NH4+ > Na+ > Cl- > K+ > Ca2+ > F- >
Mg2+. Seasonal variation of ion concentrations was significant, with the highest
concentration observed in winter and the lowest in summer. The secondary
inorganic species, including SO42-, NO3- and NH4+ (SNA) were the major components
of the water-soluble ions in PM2.5. SNA's correlations with each other were
significant. SO42-, NO3- and NH4+ were probably in the form of NH4NO3 and
(NH4)2SO4. The [NO3-]/[SO42-] ratio approaching to 1 implied that mobile sources
were as important as stationary sources. Ion balance calculations indicated
strong correlations between anion and cation equivalents. The PM2.5 was acidic.
Industrial emission, combustion process, secondary formation and fugitive dust
were the major sources of the water-soluble ions in PM2.5..
PMID- 29965287
TI - [Characteristics of Elements and Potential Ecological Risk Assessment of Heavy
Metals in PM2.5 at the Southwest Suburb of Chengdu in Spring].
AB - PM2.5 samples were collected at the southwest suburb of Chengdu in spring (in May
2012 and 2014). The mass concentrations of PM2.5 were determined by the weight
method, and 24 chemical elements in PM2.5 were analyzed by XRF. To study the
pollution characteristics and sources of chemical elements, and the potential
ecological risk of heavy metals in PM2.5, the Geo-accumulation Index, Enrichment
Factor, and Potential Ecological Risk Index methods were applied, respectively.
The results indicated that the mass concentrations of PM2.5 in spring at the
southwest suburb of Chengdu were very high, compared with American EPA's Standard
and National Standard level-II. The detection of chemical element composition in
PM2.5 showed that K and S were the main elements, whereas the contents of Ga, Cs,
Co, Cd, and V were the lowest. The differences of elemental concentrations in
PM2.5 showed relatively large differences, when compared with domestic and
foreign representative cities. Se, Cd, As, Br, S, Pb, Cl and Zn were present at
an extremely high level of geo-accumulation degree, which revealed that the
pollution coming from human activities was serious. The analysis results of
enrichment factor showed that Se, Cd, As, Br, Cl, Pb, Zn and S elements were
highly enriched or hyper accumulated, Cu, Cs, Ni, Ga and Co elements were
moderately enriched, and they were mainly from human activities rather than soil
dust. Cr, Mn, Ca and V elements were mildly enriched, and they were from both
natural sources and human activities. Na, Ti, Al, Si and Mg elements were
scarcely enriched, and they were mainly from natural sources. The ecological risk
assessment of heavy metals showed that the order of potential ecological risk
inedx of heavy metals in PM2.5 was Cd > As > Pb > Cu > Zn > Ni > Co > Cr > Mn > V
> Ti, while the ecological harm degree of Cd was extremely strong, and the whole
potential ecological risk degree was very strong.
PMID- 29965288
TI - [Geochemical Characteristics and Source Apportionment of Rare Earth Elements in
the Dustfall of Quanzhou City].
AB - Rare earth elements (REE) have certain properties as tracing elements which
result in their special geochemical characteristics. In order to study the
geochemical characteristics of REE in the dustfall and their sources, 34 dustfall
samples were collected in five functional areas and potential source areas of
Quanzhou City, then REE compositions, distribution patterns and characteristic
parameters were analyzed together with ternary diagrams and characteristic
parameter diagrams, for investigating the main provenance. The results showed
that ?REE in the dustfall presented significant spatial difference with the
sequence of industrial area>heavy traffic area > commercial area > residential
area > agricultural area. The lower coefficient variation of ?REE in residential,
heavy traffic, commercial areas indicated homogeneous sources of REE. The
chondrite-normalized REE patterns were all of the rightward inclined type with
the enrichment of LREE relative to HREE and showed obvious negative Eu anomalies
which indicated that the dustfall in study area had obvious terrigenous property.
Some REE characteristic parameters in each functional area were close to the
average in potential source areas, failed to reveal the causes for spatial
differences. The results of LaCeV diagram demonstrated that REE in the dustfall
of residential area, heavy traffic area and commercial area were mainly derived
from traffic source and soil dust, followed by coal combustion, deltaEu vs. ?REEs
diagram and HREEN/MREEN vs. LaN diagram further explained that vehicle emission
was the main anthropogenic source of REE in the dustfall of heavy traffic area
and commercial area. The REE in the dustfall of Quanzhou City was less affected
by steelworks emissions and cement plant dust and there were additional REE
sources in the dustfall of industrial and agricultural area different from other
functional areas.
PMID- 29965289
TI - [13 C-based Sources Partitioning of Atmospheric CO2 During Youth Olympic Games,
Nanjing].
AB - Observations of urban atmospheric CO2 molar fraction and its 13 C isotope
composition (delta13 C) is of great importance to interpret the effect of
anthropogenic and biologic sources on local or regional carbon cycle. High
frequency in-situ observation on atmospheric in urban airsheds was performed
during Youth Olympic Games (YOG) in Nanjing. The hourly, diurnal and daily
differences of CO2 concentration and its delta13 C between the period with and
without temporary CO2 emission controls were compared. The results showed that
short-term emission reduction measures could cause 21*10-6 decrease in
atmospheric CO2 concentration in a regional and short-term scale. The reduction
of coal combustion during YOG in YRD was about 5%. The overall isotopic signature
of local surface sources delta13 CS in Yangtze River Delta (YRD) was determined
by Miller-Tans, and the isotopic signatures of anthropogenic and natural sources
in YRD were also determined based on literature investigation. According to the
above results, the surface net CO2 flux, plant flux and anthropogenic flux in YRD
were quantified using mass-balance equation. The CO2 emission from cement
production (non-energy industrial process) was the key human factor of high
atmospheric delta13 C of CO2 in YRD during summer (2.360/00). The plant effect
could offset 23% to 39% anthropogenic CO2 emission in YRD during summer. In this
study, we tried to provide new solution to partition carbon sources in urban
areas by combining top-down atmospheric observation and traditional IPCC's
emission inventory.
PMID- 29965290
TI - [Gaseous Emission Characterization of Civil Aviation Aircraft During Takeoff].
AB - During takeoff, high engine thrust and large fuel consumption are required to
produce enough power for aircraft lift-off which has more impacts on human health
and environment than the other activities. Boeing 737-800 was selected as a
typical type in the study. Based on simulation of aircraft performance, air
pollution emissions were accurately calculated for different takeoff processes.
According to the results, NOx was the most abundant emission during takeoff.
Emissions of NOx, CO, HC, and SO2 during takeoff with normal method were 4.849,
0.062, 0.031, 0.229 kg respectively. The assumed temperature method could be used
to reduce thrust by setting an assumed temperature which was greater than actual
temperature. This method resulted in decreased NOx emission and increased CO
emission. And emissions of HC and SO2 had no significant changes. Compared with
these results, the emissions calculated by ICAO emission model led to relatively
large errors. And the emission level of normal takeoff method was approximately
equal to the emission level of small cars traveling 9508 km. The modified model
provides the basis for the accurate estimation of the air pollution emission
inventory of airport.
PMID- 29965291
TI - [Pollution Characteristics of Antibiotic Resistant Bacteria from Atmospheric
Environment of Animal Feeding Operations].
AB - Animal feeding operations is considered as a source of airborne human pathogens
and antibiotics genes. In this study, we investigated the concentration, size
distribution and aerodynamic diameter of airborne bacteria, tetracycline
resistant bacteria and erythromycin resistant bacteria from 22 animal feeding
operations in three districts of Beijing. The results indicated that the highest
and lowest concentrations of these three types of bioaerosol were detected in pig
and cow house, respectively. The concentration of airborne bacteria was higher in
layer house, whereas concentration of antibiotic resistant bacteria was higher in
broiler house. Tetracycline and erythromycin resistant bacteria were detected
from the atmospheric environment from out door of layer and broiler house with
the percentages of 8.81%, 15.89% and 23.19%, 36.53%, respectively. The size
distribution and aerodynamic diameter varied from inside and outside of pig, cow,
and layer and broiler house. Most of tetracycline resistant bacteria and
erythromycin resistant bacteria from current four types of animal feeding
operations mainly deposited in pharynx, larynx and bronchus of respiratory
system. This study would offer the base data for evaluating the detriment of
bioaerosol from animal feeding operations to the worker and environment.
PMID- 29965292
TI - [Removing Nano Particles by Filtration Using Materials with Ordered Mesoporous
Structure].
AB - The usage of porous materials to remove Nano Particles (Nanoparticles, NPs) is
one of the critical ways to purify the air. The present study employed three
typical mesoporous structures, CMK-3, SBA-15 and MCM-41 to conduct removal
experiments, in which NPs were generated, ranging from 2 nm to 20 nm, aiming at
exploring the practical feasibility and relative theory foundation about the
filtration of mesoporous structures towards NPs. Based on the physical and
chemical characterization of the three mesoporous structures above, coupled with
the adsorption experiments, the results acquired indicated that the most probable
pore size of mesoporous structures coupled with certain mesoporous capacity of a
mesoporous structure are the key to remove NPs. However, the distribution of
micropore contributed hardly to the removal of NPs. Based on this, exploration
was made to observe the effect that different flow rates and thicknesses had on
the efficiency of NPs removal. The consequences showed that most penetrating
particle size (MPPS) of NPs decreased with the increase of flow rates. Meanwhile,
the corresponding removal efficiency of MPPS decreased. Furthermore, MPPS did not
change with the change of thicknesses. This study provided technical evidence for
the removal of NPs on mesoporous structures.
PMID- 29965293
TI - [Emission Characteristics of Gaseous Pollutants from City Bus Fueled with
Biodiesel Based on DOC+CDPF Technology in Real Road Conditions].
AB - The gaseous emissions of stage III standard City bus with and without DOC+CDPF
after-treatment fueled with biodiesel blends on real road in steady-state and
transient conditions were studied using OBS-2200 gaseous portable emission
measurement. The results showed that B20 led to a decrease of CO and THC emission
rates compared with those of B0. In steady-state condition, CO and THC average
mass emission rates of B20 decreased by 26.43% and 10.44% respectively and in
transient condition the decrease rates were 22.78% and 4.95%. Meanwhile, B20
eventuated in higher CO2 and NOx emission rates. In steady-state condition, CO2
and NOx average mass emission rates of B20 increased by 8.41% and 8.26%
respectively and in transient condition the increase rates were 7.15% and 9.13%.
DOC+CDPF caused a more obvious reduction of CO and THC emission rates of B20
compared with B0. In steady-state condition, CO and THC average emission rates
decreased by 60.58% and 79.92%, while in transient condition they decreased by
63.67% and 82.57%. The influence of DOC+CDPF on emission reduction of CO2 and NOx
was not obvious.
PMID- 29965294
TI - [Characteristics of Methane Flux Across the Water-air Interface in Subtropical
Shallow Ponds].
AB - Five shallow ponds of Yichang were selected to illustrate the characteristics of
methane(CH4) in subtropical eutrophic shallow ponds. CH4 flux across the water
air interface was quantified with static floating chamber method for one year.
Annual CH4 fluxes of the five ponds were 4.495, 12.702, 6.827, 8.920, 17.560
mg.(m2.h)-1 respectively. Diffusive CH4 fluxes were 0.075, 0.087, 0.118, 0.086,
0.151 mg.(m2.h)-1 respectively and bubble emissions were 4.420, 12.616, 6.709,
8.834, 17.409 mg.(m2.h)-1 respectively. Over 98% of total CH4 flux was bubble
emission and CH4 flux was apparently higher than other aquatic ecosystems. So the
CH4 flux of shallow waters was high and bubble emission was the dominant way. CH4
emission would be largely underestimated if the research only focus on the
diffusion discharge and ignore the bubble emission.
PMID- 29965295
TI - [Succession of Phytoplankton Assemblages and Its Influencing Factors in Tangpu
Reservoir, Zhejiang Province].
AB - In order to explore the spatial-temporal dynamics of phytoplankton assemblages
and its influencing factors in Tangpu Reservoir, phytoplankton and environmental
variables were monthly monitored in 2011. The results showed that a total of 115
species of phytoplankton were identified, which belonged to 7 phyla and 62
genera. Phytoplankton abundance varied monthly with the maximum value (20.88*106
cells.L-1) in April and minimum (0.59*106 cells.L-1) in June. Variation
partitioning of species data matrix showed that the variation of phytoplankton
communities among months (account for 72.3%) was much larger than that among
sampling sites (account for 2.5%), which indicated that phytoplankton communities
had a high temporal but low spatial heterogeneity. Dominant species showed a
marked seasonal succession pattern: diatom and blue-green algae species in
spring, blue-green algae and green algae species in summer, diatom and
cryptomonads species in autumn and winter. Result of multivariate analysis (RDA)
indicated that HRT was the key factor affecting the shift between hydrological
disturbance sensitive and tolerant species, and the formation of spring algal
bloom; SiO2, WT and N:P were the key factors affecting the shift from diatom and
cryptomonads species to blue-green algae and green algae species.
PMID- 29965296
TI - [Responses of Physiological Indices of Typical Submerged Macrophytes to Water
Quality in Taihu Lake].
AB - It was well known that physiological indices of submerged macrophytes could
reflect change of water quality. The correlation between physiological indices of
submerged macrophytes and change of water quality was studied under the
cooperation of in-situ monitoring and lab analysis, combined with measuring
Chlorophyll and free proline (PRO) contents as well as peroxidase (POD)
activities in the leaves of Potamogeton wrightii Morong and Potamogeton crispus
L. under different water quality and nutrition status. The results showed: 1there
were significant spatial differences among water factors and the comprehensive
eutrophication index (TLI) of distribution areas of Potamogeton wrightii Morong
and Potamogeton crispus L. Mesotrophic water was more suitable for the growth of
Potamogeton wrightii Morong, while Potamogeton crispus L. grew well in eutrophic
water. 2there were significant spatial differences among physiological indices of
Potamogeton wrightii Morong and Potamogeton crispus L. in Taihu Lake. Besides,
there were significant relationships between Chlorophyll contents, POD activities
of two species and TLI. 3water transparency as well as nitrogen and phosphorus
nutrition were important factors leading to changes in Chlorophyll contents and
POD activities of Potamogeton wrightii Morong and Potamogeton crispus L.. The
findings from this study indicate that physiological properties of Potamogeton
wrightii Morong and Potamogeton crispus L. have a very close correlation with
nutrition status and physiochemical properties of water.
PMID- 29965297
TI - [Optical Characteristics of Dissolved Organic Matter from Two Different Full
Mixed Reservoirs in Winter Based on UV-vis and EEMs].
AB - The differences in the resource and characteristics of DOM between Zhoucun
Reservoir and Jinpen Reservoir were studied by fluorescence ultraviolet-visible
(UV-vis) and excitation-emission matrix spectra combined with parallel analysis
(EEMs-PARAFAC). The results showed that three fluorescent components were
identified by PARAFAC model in Zhoucun Reservoir and Jinpen Reservoir, including
long wave humus-like component (C1: 350/460 nm), visible fulvic-like (C2: 335/410
nm) and protein-like (C3: 260,285/360 nm). However, the fluorescence intensity
and the relative proportions of DOM exhibited significant difference (P<0.01) in
two reservoirs. Moreover, the concentration of protein-like component in Zhoucun
Reservoir was higher than that in Jinpen Reservoir, while the concentration of
humus-like component presented the opposite trend. Based on the comparison of
fluorescence index, biological index, humification index and the freshness index,
the DOM of Zhoucun Reservoir where the land-use type was cultivated, livestock
and residential, the internal pollution of sediments was serious, indicating a
strong autochthonous component and aquatic bacterial origin, whereas the DOM of
Jinpen Reservoir dominated by forest system had a higher terrigenous contribution
in winter. From all the results, hydrological conditions of the reservoir and the
characteristics of coastal ecological environment were important factors to
influence the DOM sources and characteristics.
PMID- 29965298
TI - [Hanfeng Pre-dam Commissioning Eutrophication Status and Control Evaluation in
Three Gorges Reservoir].
AB - To reduce the impact of Fluctuating Zone, the Three Gorges Reservoir pre-dam is
rare in the world which is specially designed and is the largest artificial lake
body in China. The ecological benefits of landscape, farmland and lake and the
social benefits of livable city have been significantly enhanced since the
successful commissioning of the Hanfeng Lake pre-dam system. The paper proposed
the application of layered hydrology and water quality monitoring for analysis of
Tributary runoff and lake body section in the pre-dam commissioning in the whole
year, and a total of 17 measured indicators inlucding hydrological parameters
such as v, H, etc, physical parameters such as T, pH, SD, DO, TSS etc. and
chemical parameters such as permanganate index, Chl-a, TN, DN, NO3--N, NH4+-N,
NO2--N, TP, DP, SRP etc. We found that the water quality was poor during
beginning drain and impoundment period and was the worst in tributary inflow
section of South River, while the best water quality was located in water section
of regulating dam in February and October. The TLI Water Quality Evaluation and
factor analyses performed have shown that the water body of Hanfeng Lake was
slightly eutrophicated, and the main pollution indicators included DN, TN, NO3-
N, TP. By the control of pre-dam in three Gorges to eutrophication in
commissioning, we found that the average Chl-a reduction effect reached up to
57.73%, the average reduction rate of permanganate index was 28.12%, SRP, TP, TN,
TSS, NO2--N, DN, DP etc. were on average cut down by 20.15%-22.81%, the average
reduction rates of NH4+-N and NO3--N were 16.92%-18.74%, and the average
eutrophic index of water body was reduced by 15.74%. The highest reduction
average rate in lake form period appeared from January to March and October to
December, and the lowest in river form period was during May to August.The
analysis results showed that the commissioning of pre-dam was good and remarkable
for controlling eutrophication, and cutting the concentrations of pollutant water
storage in the Three Gorges.
PMID- 29965299
TI - [Occurrence, Distribution and Ecological Risk of Aantibiotics in Surface Water of
the Gonghu Bay, Taihu Lake].
AB - In order to assess the contamination degree and ecological risk of antibiotics in
Gonghu Bay, Taihu Lake, the contamination characteristics of four kinds of
antibiotics (tetracycline, quinolones, sulfonamides and macrolides) in surface
water of the Gonghu Bay were analyzed using high performance liquid
chromatography and tandem mass spectrometry (HPLC-MS/MS). The results showed that
13 of the 16 target antibiotics were detected in the Gonghu Bay. The mass
concentrations of the 13 antibiotics ranged 0.005-4.720 MUg.L-1, and OTC was of
the highest concentration. The detection level of antibiotics was also different
between the northern and the southern parts of Gonghu Bay, and the mass
concentration of tetracycline in the northern part was higher than that in the
southern part. Moreover, the concentrations of quinolones and sulfonamides in the
southern part were larger than those in the northern part. The potential
ecological risks of the detected antibiotics were assessed via using the risk
quotients (RQs) approach. The preliminary results showed that 5 kinds of
antibiotics: OTC, NOR, OFL, CIP and ENR were at high risk, accounting for 38.5%
and 4 kinds of antibiotics TC, CTC, ROX and SMX were at medium risk, accounting
for 30.8% in the antibiotics detected in Gonghu Bay, while the others (SMR, SMP,
SQX, TMP) were at low risk. Ecological risk assessment revealed that some risks
were present in antibiotics in the Gonghu Bay. The tetracyclines and quinolones
were particularly prominent, which should be drawn enough attention, and
corresponding preventive measures should be taken as well.
PMID- 29965300
TI - [Distribution Characteristics of n-alkanes in Sediment Core and Implication of
Environment in Different Lakes of Dianchi].
AB - In order to study the composition and environment significance of the organic
matter in Lake Dianchi, samples from two sediment cores from the northern and
southern parts of the lake were collected in July, 2014. Meanwhile, the vertical
distributions of total organiccarbon (TOC), total nitrogen (TN), n-alkanes
fractions were investigated. The results showed that 1 the concentrations of TOC
and TN had been clearly increasing since the 1970s, which implied that the
primary productivity of Lake Dianchi was continuously enhanced; 2 The values of
the parameter n-C27/n-C31, Paqand CPI indicated the alternation between herbs and
woody plants from the bottom up in Lake Dianchi sediments. Besides, the high
carbon number of organic matter in sediments mainly originated from endogenous
submerged floating and large plants; 3 The index of C/N and distribution
characteristics of n-alkanes suggested differences in the various sources of
organic matter in different lakes. In detail, organic matter came from
terrigenous organic matter of anthropogenic sources and endogenous bacteria in
the sediments of northern Dianchi, while organic matter was derived from
endogenous aquatic and terrestrial higher plants mixed source in the sediments of
southern Dianchi. Finally, it is worthwhile to emphasize further research on
organic matter in different lakes of Lake Dianchi.
PMID- 29965301
TI - [Vertical Distribution and Pollution Risk Assessment of Nitrogen, Phosphorus, and
Organic Matter in Sediment of Inflowing Rivers of Erhai Lake Estuarine Wetland in
Wet and Dry Seasons].
AB - The estuarine wetland of Luoshijiang River, which flows into Erhai Lake in Yunnan
province, was regarded as the typical research object. Sediment samples in the
estuarine wetland of Luoshijiang River were collected by the cylindrical sediment
sampler and the samples were from surface layer (0-10cm), middle layer (10-30
cm), and bottom layer (30-60 cm). The vertical distribution of total nitrogen,
total phosphorus, and total organic material in dry and rainy season was analyzed
and contamination risk assessment of sediment was accomplished. The results
showed that: 1 In dry season, average concentrations of total nitrogen in
sediment on surface, middle and bottom layer at estuarine wetland of Luoshijiang
River were respectively 1.734, 1.453 and 1.255 g.kg-1, the average concentrations
of total phosphorus were respectively 1.085, 1.034 and 0.992 g.kg-1, the average
concentrations of organic material were respectively 59.051, 47.730 and 42.133
g.kg-1. In rainy season, average concentrations of total nitrogen in sediment on
surface, middle and bottom layer at estuarine wetland of Luoshijiang River were
respectively 1.147, 0.948 and 0.895 g.kg-1, the average concentrations of total
phosphorus were respectively 0.599, 0.523 and 0.519 g.kg-1, the average
concentrations of organic material were respectively 53.098, 46.897 and 43.395
g.kg-1. 2 Single factor pollution index, organic nitrogen and organic index
assessment were used to evaluate the contamination level of sediment, the
assessment results showed that: In dry season, the contamination level of
nitrogen and phosphorus in sediment was on severe level, organic material
contamination was on medium level. In rainy season, the contamination levels of
ON and OI were medium, and that of PI was mild. Generally, the contamination
levels of nitrogen, phosphorus and organic material in sediment tendency were as
follows: dry season>rainy season, and the pollution index of each layer followed
the sequence of surface layer > middle layer > bottom layer, and the most
extraordinary contamination of them on surface layer was uncovered whatever the
season was. 3 Pollution origin of estuarine wetland of Luoshijiang River in dry
and wet season had great differences, it was mainly the exogenous source in dry
season, but it was the internal source in wet season; The potential risk of
release of nutrient salt of sediment in dry season was higher than the wet, and
the risk in the surface layer was the highest.
PMID- 29965302
TI - [Variation of Nitrogen Forms in Sediments of Lihu Lake During Mineralization].
AB - After 10 years of controlling point source sewage in Lihu Lake, the total
nitrogen in water is still at a higher level. To explore the effects of sediment
nitrogen release on overlying water, the method of submerged water cultivation
was used to study changing characteristics of different nitrogen species in the
process of sediment mineralization and the exchange between organic nitrogen and
inorganic nitrogen of the mineralization process transformation process was
discussed. The results showed that, the mean value of free nitrogen(FN) increased
from 94.26 mg.kg-1 to 230.71 mg.kg-1 after nitrogen mineralization in the
sediment, when ammonium and solved organic nitrogen (SON) were dominant; the mean
value of exchangeable nitrogen (EN) increased from 82.50 mg.kg-1 to 165.32 mg.kg
1 with ammonium being the main species; the mean value of acid solution nitrogen
(HN), which gave priority to amino acid nitrogen (AAN), decreased from 1044.70
mg.kg-1 to 815.93 mg.kg-1, and residual nitrogen (RN) basically remained
unchanged. In the submerged cultivation process, acid solution state of total
nitrogen fell from 67.18% to 52.50%, the reduction was mainly caused by
mineralization and decomposition of AAN and ammonium nitrogen (AN), moreover, AAN
was one of the most effective sources of inorganic nitrogen after sediment
mineralization. Comparison of the results of estuaries and lakes showed that, the
larger the amount of sediment was, the more the mineralized inorganic nitrogen
was.
PMID- 29965303
TI - [Temporal and Spatial Variation Characteristics of the Heavy Metals Content in
the Surface Sediment and the Potential Ecological Risk Trends in the Three Gorges
Reservoir Area].
AB - With the construction progress of the Three Gorges Project, the hydrological
situation of Three Gorges Reservoir changes greatly, which causes the changes of
suspended solids precipitation conditions and surface sediment traits. This
research analyzed the temporal and spatial variation of the heavy metal pollution
in the surface sediment and the potential ecological risk trends during the years
from 2000 to 2015 in the trunk stream of the Yangtze River from Jiangjin to the
Three Gorges Dam area and some major tributaries, such as Jialing River, Yulin
River, Wujiang River, Xiaojiang River, Xiangxi River. The results showed that the
average content ranges of heavy metals (including Cu, Pb, Mn, As, Hg etc.) in
surface sediments at the main stream monitoring sections during the study period
were 46.5-85.7 mg.kg-1(Cu), 43.8-65.1 mg.kg-1(Pb), 784.2-910.6 mg.kg-1(Mn), 8.44
11.91 mg.kg-1(As), 0.193-0.236 mg.kg-1(Hg) respectively; The average content
ranges of the heavy metals in surface sediments at the main stream monitoring
sections during the study period were 16.5-85.6 mg.kg-1(Cu), 25.8-74.8 mg.kg
1(Pb), 573.7-996.3 mg.kg-1 (Mn), 6.96-13.31 mg.kg-1 (As), 0.160-0.232 mg.kg-1
(Hg) respectively. The results also showed that there were obvious differences of
the heavy metals content in some areas between the left and right bank of the
trunk stream of the Yangtze River in the Three Gorges Reservoir area. The results
also showed that the concentration variation trends of the heavy metals were
different in the surface sediments, such as Cu, Pb, Mn, As and Hg. The content of
Hg was the most influenced element by the water period effect. The concentration
variation trends of these elements were different at different monitoring
sections during the construction and water harvesting progress of the Three
Gorges project. The contents of Cu, Pb, Mn and As in sediment from the Three
Gorges Reservoir area showed strong positive correlations between each other. But
there was a low correlation between the content of As and those of other
elements. There was no significant correlation between the content of Hg and
those of other heavy metal elements. According to the geoaccumulation index
analytical method, the contents of the heavy metals in surface sediments in the
Three Gorges Reservoir area were generally at low enrichment level. But the
pollution caused by Hg should be paid attention. The change of potential
ecological risk index was small in the main stream and the major tributaries of
the Yangtze River (except Wujiang River) in most of the time. It should also be
noted that the change of potential ecological risk index fluctuated obviously at
a high level before the year of 2008, and then the change fluctuations trends
descended with time and tended to be stable.
PMID- 29965304
TI - [Modeling the Environmental Behaviors and Ecological Risks of Permethrin in
Chaohu Lake].
AB - Environmental pollution caused by synthetic pyrethroid insecticides has received
a great deal of attention with the increase in usage recently.To understand the
occurrence, environmental processes, fate and ecological impact of permethrin in
Chaohu Lake, fugacity based multimedia fate model combining species sensitivities
model (SSD) were employed.The concentration distribution, and transfer fluxes
were predicted under nonequilibrium steady-state condition, and the effect of
input parameter on the outputs was evaluated by sensitive and uncertainty
analysis.Furthermore, SSD model of aquatic organisms was constructed for
permethrin to assess the potential ecological risk and to determine the maximum
annual input amount of permethrin for the purpose of protecting 95% of
species.The results showed that the predicted concentrations of permethrin in
air, water and sediment were 3.99*10-16, 5.63*10-11, 1.95*10-5mol.m-3, and
sediment was the largest sink.Most permethrin was transported from water to air
via volatilization, but elimination from air was mostly by particle dry
deposition.Permethrin in water was predominately from advection, and was removed
by deposition of suspended particulate matter.Sediment associated permethrin was
generally derived from suspended particulate matter deposition, and was
eliminated by resuspension and sediment burial.The results of SSD model suggested
HC5 value was at 0.97 ng.L-1, which was much higher than the predicted
environmental concentration of permethrin in water.Only 0.77% of species was
possibly impacted by exposure to permethrin.In order to protect 95% of species in
Chaohu Lake, the maximum annual input amount of permethrin should be controlled
below 78.2 t.a-1.
PMID- 29965305
TI - [Simulation Experiment: Effect of Organic Colloid on Carbamazepine Transport in
Porous Media].
AB - The behavior of organic contaminants in subsoil can be affected by their
interactions with organic colloids. In order to explore the impact of organic
colloids on the mobility of emerging contaminants in porous media, especially
pharmaceutical and personal care products (PPCPs), column experiment was
conducted to investigate the migration behavior of target compound carbamazepine
(CBZ). In the experiments, quartz sand, standard soil and natural field-collected
soil were selected as three types of porous media respectively, and organic
colloids were prepared with commercial humic acid. The results showed that, the
two-site chemical nonequilibrium model in CXTFIT could better describe the
migration behavior of CBZ in all soil columns. This results demonstrated that
chemical nonequilibrium adsorption happened in CBZ's migration process. After
colloid was added to the sand column, results of CBZ's adsorption process had no
significant changes, however, desorption hysteresis was weaker. The reason for
that can be explained as the formation of colloid-CBZ complexes by the
combination of colloid with CBZ. These complexes could not significantly
influence CBZ's adsorption process, however, they could accelerate CBZ's
desorption process by solubilization. When organic colloids existed, the
migration of CBZ in natural soil and standard soil columns was more hysteretic
than sand column, indicating that the sorption capacity of soil column was higher
than sand column. The soil organic matter and clay should play a crucial role in
the transportation: low/high energy adsorption sites in organic matter and clay
surface all could bond with CBZ. Compared with standard soil, the magnitude of
sorption and desorption hysteresis of CBZ in natural soil was higher. It was
mainly because of the higher organic content in natural soil. Based on the
migration behavior of the contaminant in this study, a concept model for various
interactions during the transport of hydrophobic organic contaminants in porous
media in the presence of organic colloids was then proposed.
PMID- 29965306
TI - [Grain Size Distribution Characteristics of Suspended Particulate Matter as
Influenced by the Apparent Pollution in the Inorganic Type Urban Landscape Water:
Taking the Canal of Suzhou Section as Example].
AB - Grain size distribution characteristics of suspended particulate matter(SPM)
provides important information for water environment apparent quality. The size
distribution characteristics and influencing factors of suspended particulate
matter under different apparent pollution levels in the inorganic type urban
landscape water were discussed taking the canal which is flowing through Suzhou
as the research object. The apparent pollution mechanism of inorganic type urban
landscape water was explained from the aspect of the size of the suspended
particles. The results showed that: SPM had mainly a uni-modal distribution in
the inorganic type water, and the median particle diameter range was 13-25.2 MUm.
The component II was perdominant, and the particle size range was 3.8-16 MUm(with
an average volume fraction of 29.4%-59.6%). Sensitive components of the apparent
polluted water were component II and component IV (particle size range 32-64
MUm). The relation of the sensation pollution index(SPI) and component II was
segmented, and the node was 45NTU. When the turbidity was less than 45NTU, SPI
value and volume fraction of component II had a significant positive correlation,
and volume fraction of component IV had a significant negative correlation with
SPI value; when the turbidity was equal to or greater than 45NTU, the correlation
was the opposite. The influencing factors of particle size distribution of Suzhou
canal mainly included organisms and hydrodynamic conditions. The biological
factors mainly led to increase of the algae and the hydrodynamic condition caused
resuspension and increased the large particles.
PMID- 29965307
TI - [Rock Weathering Characteristics and the Atmospheric Carbon Sink in the Chemical
Weathering Processes of Qingshuijiang River Basin].
AB - Carbon sink produced during rock weathering is critical to global carbon cycles.
In this work, the major ion chemistry and ion sources of Qingshuijiang River
Basin were investigated. The principal component analysis, mass balance approach
and deduction method were applied for estimating the weathering rate and
atmospheric CO2 consumption via the chemical weathering of rocks. The results
demonstrated that the chemical weathering of carbonate and silicate rocks within
the drainage basin was the main source of the dissolved chemical substances in
the Qingshuijiang River Basin, prior to carbonate rock weathering. Some 58.28% of
the total dissolved chemical substances were derived from the chemical weathering
of carbonate rock, 17.38% from the dissolution of silicate rock, and 17.74% from
atmospheric CO2 contribution rates. The chemical weathering rate of this
catchment was estimated to be 109.97t.(km2.a)-1, which was comparable to Wujiang
River Basin, but higher than the average of global rivers. Furthermore, the
atmospheric CO2 consumption rate was estimated to be 7.25*105 mol.(km2.a)-1. The
CO2 flux consumed by the rock chemical processes within this catchment was
12.45*109 mol.a-1, of which about 63.13%(7.86*109 mol.a-1) was resulted from
carbonate weathering and 36.87%(4.59*109 mol.a-1) from silicate weathering. The
CO2 consumed by rock chemical weathering in the Qingshuijiang River reduced the
atmospheric CO2 level and constituted a significant part of the global carbon
budget. Correlation and spatial distribution analysis of SO42-, F-, NO3- showed
that anthropogenic activities contributed remarkably to dissolved solutes and
associated CO2 consumption worldwide, and anthropogenic inputs probably
contributed some 4.87% to the dissolved solutes in the Qingshuijiang River.
PMID- 29965309
TI - [Identification of Sulfate Sources in the Groundwater System of Zaozhuang:
Evidences from Isotopic and Hydrochemical Characteristics].
AB - Karst groundwater is an important source of water supply for the industrial and
agricultural proposes and drinking water in Zaozhuang City. In recent years, with
the development of industrialization and increasing of domestic water
consumption, the sulfate pollution of karst groundwater has become a serious
problem. 36 samples of surface and different depth of groundwater were collected
in southern Zaozhuang City in August, 2014. Based on the analysis of the
hydrochemical composition and the isotopic characteristics of deltaD, delta18O
H2O, and delta34 S-SO42-, this paper analyzed the influence of hydrogeochemical
evolution of groundwater and human input in the area, in order to identify the
scope and ways of sulfate pollution. The results showed that the basic
hydrochemical type was HCO3.SO4-Ca, formation of geochemical components mainly
included the dissolution of carbonate and sulfate minerals, oxidation of pyrite
and the influence of human activities. Moreover, the main recharge of groundwater
in study area was the atmospheric precipitation. The hydraulic connection was
closely linked between the surface water and different depth of groundwater. The
variation range of groundwater delta34 S-SO42- values was from 0.20/00 to
9.30/00, and the relationship between the delta34 S-SO42- value and SO42- value
of groundwater showed different sources of sulfate. The sources of sulfate in
groundwater included the dissolution of gypsum, the oxidation of pyrite, the
leaching of fertilizer and infiltration of domestic sewage and industrial
wastewater. In addition to the original geological factors, wastewater
infiltration of industrial and mining enterprises was the main reason for the
increase of sulfate content in the groundwater.
PMID- 29965308
TI - [Pollution Characteristics Analysis in Shallow Groundwater of Typical Farmland
Area, Southern China].
AB - To analyze the characteristics of shallow groundwater pollution in farmland
ecosystem in south China and geochemical behavior of major pollutants in the
environment, taking the typical farmland in Taihu River Basin as the object,
combined with conventional analysis method of the water quality, fluorescence
spectrum technology and multivariate statistical analysis method, the
characteristics of the water chemistry in shadow groundwater and the distribution
of the dissolved organic matter and the heavy metals were studied. The reasons
for all the phenomena were researched as well. The result showed that, water body
in the study area showed the reducing atmosphere, the main chemical types of
shallow groundwater were HCO3-Ca.Na, and compared to the contents of NH3--N and
NH2--N, the concentration of NH4+-N was higher. Dissolved organic matter of the
shallow groundwater was composed of humic acid, tryptophan and tyrosine. And they
were mainly derived from terrestrial and biological source. The distribution was
affected by the flow direction of the surface water supplies and groundwater. In
the detection of nine kinds of heavy metal elements, the average concentrations
of Fe and Cr were higher than the national groundwater environmental quality in
class III standard. And the contents of Fe, Cr, Mn, Zn elements at some points
exceeded the standard. The results showed that fluorescent organic matter
characteristics could better reflect the status of shallow groundwater pollution,
in which the kind of protein-like substances was closely related to the ammonia
nitrogen. The heavy metal elements Cu and Ni were associated with the dissolved
organic matter and they were mainly complexed in small molecular fluorescent
organic matter.
PMID- 29965310
TI - [Removal of Polycyclic Aromatic Hydrocarbons by Extensive Green Roofs].
AB - In this study,four pilot-scale extensive green roof facilities with different
substrate compositions were developed. In 8 rainfall events, concentrations of 16
kinds of polycyclic aromatic hydrocarbons (PAHs) in effluent of these facilities
were investigated and compared with effluents of asphalt roofing, the blank
control roof and rain water. Average PAHs concentrations in the effluent of these
four facilities, asphalt roofing and blank control facilities were 145, 166, 151,
160, 900, 270 ng.L-1, respectively. The PAHs mass concentrations discharged by
four simulation facilities were significantly lower than asphalt roofing and
blank control roof. From the perspective of the mass loading control, all four
simulation facilities could effectively control roof runoff PAHs load with an
average load reduction rate of 71.76% compared with the blank control roof.
Interception and adsorption by green roof substrates was the main removal way for
PAHs. Facilities' PAHs removal efficiency could be improved by increasing the
substrate thickness with the same substrate composition. Transforming traditional
asphalt roofing into extensive green roof was an effective way to control PAHs
emissions from roof runoff.
PMID- 29965311
TI - [Comparative Study on Pretreatment Process of Ultrafiltration: Chemical
Coagulation and Electrocoagulation].
AB - The ultrafiltration membrane response mechanism and the effect on the membrane
fouling under dead end filtration were comparatively investigated in
ultrafiltration pretreatment processes using chemical coagulation (CC) and
electrocoagulation (EC). The effects of Al3+ dosage on the flux of the
membrane,the properties of the floc (particle size, strength coefficient,
recovery coefficient, fractal dimension) and the properties of the cake layer
were studied. The results showed that taking EC as a pretreatment method, the
flocs were stronger and more compact, the cake layer deposited on the surface was
porous and higly hydrophilic; while in CC pretreatment, the flocs were loose and
had low strength, which would be compacted and crushed easily by the pressure in
membrane filtration process, resulting in relatively dense cake layer and low
hydrophilicity. Therefore, EC was the most effective pretreatment process to
alleviate membrane fouling during operation, which could maintain a flux that was
about 5.57% higher than CC.
PMID- 29965312
TI - [Adsorption Mechanisms Analysis of EfOM on PVDF Ultrafiltration Membranes
Modified by SiO2 Using QCM-D and AFM].
AB - To further unravel adsorption mechanisms of effluent organic matter (EfOM) on the
PVDF ultrafiltration membranes modified by nano-silica particles from micro
perspective during different filtration phases, the membranes were prepared by
adjusting the dosage of nano-silicon. The adsorption of EfOM on the surface of
the membranes and the interaction between EfOM and the membranes were measured by
quartz crystal microbalance with dissipation monitoring (QCM-D) and atomic force
microscopy (AFM).The QCM-D results suggested that adsorbing capacity and
adsorption rate of EfOM on the hydrophilic surfaces were lower than on the
hydrophobic surfaces. Meanwhile, it was found that EfOM underwent adsorption via
two steps: In the initial 15 min stage, a rapid adsorption of EfOM accumulated
onto the membrane surface; The change in dissipation still occurred when the EfOM
adsorption frequency reached balance, which demonstrated that the adsorption of
EfOM remained unchanged on the membrane surfaces, and changes in the conformation
of adsorption layer still occurred. For the AFM force test, it was found that the
EfOM-membranes and EfOM-EfOM interactions declined with the increase of
hydrophily, which revealed the essential reason for the decrease of adsorbing
capacity and adsorption rate. The combined utilization of QCM-D and AFM
effectively explained the effect of modified membranes on adsorption mechanisms
of EfOM.
PMID- 29965313
TI - [Isolation of Quorum Quenching Bacteria and Their Function for Controlling
Membrane Biofouling].
AB - Interspecies quorum quenching by bacterial cells has been reported as a novel
approach for mitigating the biofouling via restraining quorum sensing(QS). Five
indigenous quorum quenching bacterial strains were isolated from activated sludge
taken from wastewater treatment plant. Strain HG10 showed high degrading activity
against C6-HSL(N-hexanoyl-L-Homoserine lactone). The result of 16S rDNA
sequencing showed that the isolated strain HG10 belonged to the genus Bacillus
cereus. Strain HG10 was immobilized in sodium alginate(SA), and the biofouling
inhibition of SA-HG10 in membrane filtration treatment system was investigated.
The results showed that the membrane flux in experimental group B(provided with
SA-HG10)was 181.29 L.(m2.h)-1, and the membrane flux in control group A (without
the beads) was 110.64 L.(m2.h)-1, The membrane flux in group B was 63.86% higher
than group A. The content of extracellular polymeric substances (EPS) in the
biofilm on the membrane filter was also measured. The results showed that the
contents of polysaccharides and proteins in the experimental group B decreased by
29% and 48% respectively than those of group A. A large decrease in the content
of hydrophobic proteins was the main reason for the decrease of membrane fouling.
The content of EPS in the membrane surface decreased by 43%, indicating that SA
HG10 could inhibit biofilm formation on the membrane filter and effectively
improve the filtering performance.
PMID- 29965314
TI - [Effects of Hydraulic Loading Rate on the Removal of Pollutants from an
Integrated Biological Settling Tank].
AB - Based on the designing concepts of rotating biological disk and settling tank, a
hybrid biological purification and settling tank was developed to achieve
simultaneous removal of turbidity causing materials, organic matters, NH4+-N, and
TP. Experimental results showed that under certain rotary speed and water quality
conditions, the removal rates of both turbidity and organic matters and NH4+-N
were relatively stable first and then started to decrease with the increase of
hydraulic loading rate. The highest value was achieved at 0.036 g.(m2.d)-1 and
0.064 g.(m2.d)-1 respectively. Compared with turbidity and TOC and NH4+-N, the
removal rate of TP was greatly influenced by hydraulic loading rate. The average
TP removal was the worst at 0.064 g.(m2.d)-1. Appropriately decreasing or
increasing the hydraulic load was helpful to the phosphorus removal process.
Further study showed that nitrification and dephosphorization processes competed
for the limited carbon source and DO in the water phase. Along the flow
direction, the surface of the disc populations of microorganisms with good
coordination and distribution along the characteristics ensured that the process
still had certain decontamination effect under the condition of unfavorable
hydraulic load, which indicated that the biological settling tank had a capacity
in resisting organic loading rate shock and could be used in enhancing pollutant
removal in treating micro-polluted water.
PMID- 29965315
TI - [Characteristics of Nitrobacteria in SBR with Trace N2H4 Addition].
AB - A sequencing batch reactor (SBR) was conducted to perform nitrification process.
The influence of long-term trace hydrazine (N2H4) addition (about 3 mg.L-1) on
ammonium oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) in
nitrifying sludge was investigated. The result indicated that Nitrosococcu,
Nitrosomonas and Nitrosospira were related to AOB, and Nitrobacter was related to
NOB in nitrifying sludge with N2H4 addition, respectively. The estimates of AOB
population (in dry sludge) with N2H4 addition decreased from 1.0*109 to 2.09*104
copies.g-1, and those of NOB decreased from 1.28*107 to 2.56*105 copies.g-1. AOB
was more sensitive to environmental factors than NOB, the effect of inhibition
and toxicity on nitrobacteria caused more loss of AOB abundances than that of
NOB, but quantitative real-time PCR could not determine the inhibition of N2H4 on
microbial activity of AOB and NOB. The nitrobacteria activity was destroyed with
long-term trace N2H4 addition, and the reactor collapsed. Consequently, it was
possibly unable to inhibit NOB activity by controlling the added N2H4
concentration, and further take off NOB in nitrification process for improving
nitrogen removal.
PMID- 29965316
TI - [Start-up of Partial Nitritation AGS-SBR and Analysis of Its Microbial Community
Composition].
AB - The mature aerobic granular sludge (AGS) was inoculated in an sequencing batch
reactor (SBR) to treat the simulation wastewater with low carbon nitrogen ratio
(COD/N). The start-up characteristics of partial nitritation (PN) based on
gradually increasing influent ammonia concentration strategy were investigated.
The reactor was operated at dissolved oxygen (DO) of 0.8 mg.L-1, pH 7.5-8.5 and
30C.The PN was realized in the AGS-SBR within 60 days. From day 61 and onwards,
the nitrite accumulation efficiency of 80% was achieved throughout the
experiment. Meanwhile, the total nitrogen average removal rate was maintained at
a relatively high level of 64.54%, and the effluent NO2--N/NH4+-N ratio reached
1.16, which was a suitable mixture to feed subsequent anammox. Finally, we also
investigated the bacterial abundances in AGS-SBR in the PN period (PN-AGS-SBR)
through Illumina 16S rRNA gene MiSeq sequencing. The dominant microbial
communities at genus level were subjected to sequence analysis. The results
revealed that the relative abundance of Candidate-division-TM7-norank was 68.63%,
Saprospiraceae-uncultured was 8.26%, Thauera was 4.63%, Denitratisoma was 3.16%,
Anaerolineaceae-uncultured was 1.63% and Anaerovorax was 1.39%, respectively.
Nitrosomonas, Thauera, Denitratisoma and Bacillu were considered as the main
organisms responsible for nitrogen removal. Meanwhile, various denitrification
pathways, such as autotrophic denitrification, the denitrification and anaerobic
ammonia oxidation of nitrogen, coexisted in PN-AGS-SBR system.
PMID- 29965317
TI - [Effects of PAHs Pollution on the Community Structure of Denitrifiers in a
Typical Oilfield].
AB - Agricultural soils in the oilfields have the potential risk of PAHs (polycyclic
aromatic hydrocarbons) pollution, and the denitrification process with nitrate as
the terminal electron acceptor might be important for soil PAHs elimination under
anaerobic condition. In this study, 9 soil samples listed as JH-1 to JH-9 were
collected from the JiangHan oilfield with a history of more than 50 years. Using
the functional genes (nirK: Cu-nitrite reductase gene; nirS: cd1-nitrite
reductase gene) involved in denitrification as biomarkers, the community
structure of soil denitrifiers was investigated by quantitative-PCR and T-RFLP
(terminal-restriction fragment length polymorphism) combined with clone library,
and the relationship between soil properties and community structure of soil
denitrifers was discussed. The result indicated that the copy numbers of nirK
were higher than those of nirS in all soil samples, and the lowest copy numbers
of nirK and nirS were both detected in the JH-4 with the highest PAHs content.
Meanwhile, the correlation analysis also showed a negative correlation between
the copy numbers of those functional genes and soil PAHs content (nirK: R2=0.54,
P<0.05; nirS: R2=0.58, P<0.05). Furthermore, the result of T-RFLP indicated that
the nirK community structures in different soil samples varied significantly,
which was obviously unique in the sample (JH-4) with the highest PAHs content.
The subsequent RDA (redundancy analysis) also demonstrated that soil PAHs content
as well as the available nitrogen and phosphorus belonged to the most important
factors affecting the nirK community structure in this oilfield soil. Compared
with nirK, little variation was shown about the nirS community structure among
the soil samples. However, the abundance of nirS-harboring pseudomonas had a
remarkably positive relation with the soil PAHs content, which indicated that
pseudomonas, a well known bacterial genus with strong ability to degrade organic
pollutants, might be an essential driver for PAHs degradation via denitrification
process in this oilfield soil.
PMID- 29965318
TI - [Performance and Microbial Community Analysis of Bioaugmented Treatment of
Diethyl Phthalate (DEP) in Membrane Bioreactor].
AB - To enhance the degradation of DEP, the DEP-degrading bacterium Arthrobacter sp.
LMS13 isolated from activated sludge was inoculated in MBR reactor to investigate
the DEP removal efficiency. At the same time, the real-time quantitative PCR and
Illumina MiSeq high-throughput sequencing techniques were employed to detect the
changes of phthalate dioxygenase gene (phtA) and the bacterial community
structure in the process of reactor operation. The results showed that
bioaugmented system shortened the start-up time, and the DEP removed rate of
bioaugmented system and unbioaugmented system was 81% and 19%, at concentration
of 800 mg.L-1, respectively. PhtA copies increased during domestication, but
dropped when DEP concentration exceeded 400 mg.L-1. The phtA gene abundance and
DEP removal rate were positively correlated. Bacteria community analysis showed
that, along with the operation of reactor, the abundance of phylum of
Bateroidetes and Firmicutes reduced, epsilon-Proteobacteria and Chloroflexi
gradually disappeared in the system; on the contrary, beta-Proteobacteria and
Actinobacteria became the dominant phyla in reactor. Rhodocyclus, Bordetella and
Arthrobacter were dominant in the DEP degradation system, and probably maintained
the stable operation of reactor.
PMID- 29965319
TI - [Comparative Analysis of the Bacterial Community on Anodic Biofilms in Sediment
Microbial Fuel Cell Under Open and Closed Circuits].
AB - To investigate the differences in microbial community of anodic biofilms under
open and closed circuits, sediment microbial fuel cell (SMFCs) reactors
connecting with a 5 kOmega external resistance and open circuit during the start
up period were operated individually. Anodic biofilms were collected and analyzed
using Solexa high-throughput sequencing technology. A total of 3936 and 3930
operational taxonomic units (OTUs) were obtained from the anodic biofilms under
open and closed circuits, respectively. After 97% similarity merging, 1581 and
1551 OTUs were finally determined from open and close circuit biofilms,
respectively. The analysis of alpha diversity showed that bacterial diversity of
anodic biofilm under open circuit was higher than that under closed circuit. The
dominant bacterial were Proteobacteria, Firmicutes and Bacteroidetes for both
open and closed circuits. They accounted for 59.79%, 12.54% and 9.02% under open
circuit biofilm respectively; and these values were 63.02%, 10.01% and 3.60% in
the closed circuit biofilm respectively, and Geobacter accounted for 16.55% in
the closed circuit biofilm. The present study demonstrated that the electron
transfer process during start-up period affected the microbial community
structure of the anodic biofilms.
PMID- 29965320
TI - [Anaerobic Biodegradability of Perfluorooctanoic Acid (PFOA)].
AB - Perfluorooctanoic acid (PFOA), one of the most typical representatives of
perfluoroalkyl surfactants (PASs), has relatively high detection rate and level
of pollution, and the accumulation of PFOA in the environment has been a serious
threat to human health and security of the whole ecological environment.
Therefore, studies on anaerobic biodegradability of PFOA are very important for
elucidation of its environmental fate. This study used anaerobic sludge from
municipal sewage treatment plant (WWTP) and 5.0 mg.L-1 vitamin B12 (VB12) as
catalysts for the degradation of PFOA in the anaerobic environment. The anaerobic
biodegradability of PFOA was examined by liquid chromatography tandem mass
spectrometry (LC-MS/MS) and ion chromatography while some indictors, such as
molar recoveries of PFOA as well as concentrations of fluoride, acetate, 2H-PFOA
(F(CF2)6CHFCOOH), and shorter chain (0.05). Compared with nonfertilized treatment, soil CO2
cumulative emissions of the whole growth period with application of nitrogen
fertilizer (210 kg.hm-2), phosphate fertilizer (63 kg.hm-2) and nitrogen mixed
with phosphate fertilizer (210 kg.hm-2, 63 kg.hm-2) were significantly increased
by 23.70%, 19.00% and 12.30%, respectively. And interaction effects between
nitrogen and phosphorus fertilizer were extremely significant (P<0.01). Variance
analysis of the interaction of water and fertilizer showed that the average soil
CO2 fluxes of the whole growth period were not statistically significant but
cumulative emissions of soil CO2 were significant (P<0.05) when the difference of
supply level was 15%. In addition, soil CO2 flux and cumulative emission in the
whole growth period were significant when supply differed by 30%. Obviously, soil
CO2 emissions were promoted significantly by application of irrigation amount,
nitrogen fertilizer, phosphorus rate and water and fertilizer interaction, while
it was inhibited by nitrogen mixed with phosphorus. It was effective to regulate
soil CO2 emission by water and fertilizer controlling measures.
PMID- 29965322
TI - [Spatial Heterogeneity of Soil Respiration in the Soil Erosion Area of West
Mountains in Fujian Province, China].
AB - The spatial heterogeneity of soil respiration (Rs) is of great significance in
accurately estimating the carbon budget in erosion areas. This study investigated
the soil respiration (Rs), total nitrogen (TN), carbon-nitrogen ratio (C/N), soil
organic carbon content (SOC), leaf area index (LAI), soil temperature (T10), and
soil moisture (W) in 59 soil samples collected from Hetian Town in Fujian
Province. Both classical statistics and geostatistics were used to analyze the
spatial heterogeneity of soil respirations and other measured factors. The
variability of Rs and other measured factors in the samples ranked from the
largest to the smallest: LAI > SOC > TN > Rs > C/N > T10 > W. Rs was positively
correlated with T10 (P<0.01) and with TN (P<0.05), but not significantly
correlated with other factors (P>0.05); TN, SOC and T10 could be used to explain
the spatial variation of soil respiration among the samples. The results from geo
statistical analysis showed that Rs was in a medium spatial autocorrelation, with
52.89% of spatial heterogeneity caused by structural factors and 47.11% of
spatial heterogeneity resulted from random factor; the fractal dimensions of soil
respiration and its interacted factors were ranked as: Rs > LAI > C/N > T10 > SOC
> W > TN; the spatial distribution patterns of Rs were similar with those of TN
and T10, but different from those of C/N, SOC or LAI. At the 95% confidence level
and 90% estimation accuracy, the reasonable sampling number of Rs was 62.
PMID- 29965323
TI - [Comprehensive Risk Evaluation of Cadmium in Soil-rice System Based on
Uncertainty Analysis].
AB - Cadmium (Cd) can cause adverse health effects and is a subject of concern in rice
consumption. The uncertainty analysis helps improve the accuracy in the risk
assessment for Cd in soil-rice system. A regional investigation on Youxian
prefecture, southern China, was conducted to analyze the Cd concentration in
rice. Based on the species sensitivity distribution model (SSD), health risk
assessment model, and Monte Carlo simulation, the accumulation characteristic of
Cd in soil-rice system, accumulation risk of Cd in soil, and health risk of Cd
concentration in rice were determined. The results showed that the plant uptake
factor (PUF) of Cd of rice was well fitted by the SSD model. The mean level of
PUF was 1.86, with a significant spatial heterogeneity. The rice produced in WL
county tended to accumulate a high level of Cd. There was no significant
relationship between concentrations of Cd in soil and rice, suggesting that of
rice renders the Cd risk management very difficult. The pollution load index of
Cd in soil was 2.4, which belonged to a moderate contamination level. Under
current accumulation condition of Cd in soil, there would be a 90.4% probability
for soil Cd concentration to be higher than the national soil quality standard
after 10 years. Health risk assessment showed that the average daily dose (ADD)
was 2.9 MUg.(kg.d)-1, 3.5 fold higher than the WHO limit. About 93.9% of the
adult populations consuming rice cropping in affected areas had the risk that the
daily Cd intake was above the WHO limit. The health risk index (HRI) was around
2.1 to 4.7. The probability for health risk index (HRI) higher than 5 was 21.5%,
suggesting a high health risk. When the soil pH was lower than 5.5, the
probability for HRI higher than 1 was 95.3%, and when the soil pH was higher than
6, the probability for HRI higher than 1 reduced to 68.1%. An improved management
of soil pH values would be needed for a better and safer rice production. The
combination of uncertainty analysis, species sensitivity model and health risk
assessment model was validated to be feasible and reliable in the risk analysis.
PMID- 29965324
TI - [Fluorescence Properties of Glomalin and Its Relationship with Soil
Physyicochemical Characteristics in Different Regions of Beijing City].
AB - Glomalin-related soil proteins (GRSP), which has been used as a presumable
biological indicator of soil quality, is of vital ecological importance. In this
research, we tested the GRSP content and physicochemical property of soils
collected in mountain, urban and suburb areas of Beijing City. Besides, the
fluorescence property of GRSP was also studied by using EEM-PARAFAC. The results
showed that GRSP could be decomposed into five compounds, terrestrial humic-like
substances UVA, terrestrial humic-like substances UVC, oxidized quinones, soil
fulvic acid and amino acids. The GRSP content and protein-like fluorescence
substances in urban and suburb areas significant decreased and oxidized quinones
content elevated in comparison with those in mountain area. The physicochemical
property was also shaped by urbanization. Compare to mountain area, moisture
content, total organic matters and total nitrogen significantly decreased in
urban area soil and suburb area. GRSP content, terrestrial humic-like substances
UVA and oxidized quinones content showed significant correlation with soil
organic matter and total nitrogen. Base on that, an integrated index system
mainly consisting of GRSP concentration and C1 component and C3 component was
recommended to evaluate the soil health status.
PMID- 29965325
TI - [Spatial Distribution Characteristics of Heavy Metal Pollution and Health Risk in
Soil Around the Coal Industrial Area of East Junggar Basin].
AB - The soil around the coal industrial area of East Junggar Basin in Xinjiang was
studied. A total of 64 soil samples were collected from the 0-10 cm, 10-20 cm, 20
30 cm layers of soil profile, and the contents of Zn, Cu, Cr, Pb, Hg and As were
tested, respectively. Pollution Load Index(PLI) was employed to assess the heavy
metal contents and the model of health risk assessment recommended by USEPA was
adopted to evaluate the health risk due to exposure to heavy metals in different
soil depths. The multivariate statistical analysis, geostatistical analysis and
GIS technology then were used to study the differences, spatial variability
structure and distribution pattern of the evaluated results, and cross-validation
method was adopted to assess the prediction results and its stability. The
results suggested that the ranges of Zn, Cu, Pb contents were 46.06-48.00 mg.kg
1, 18.37-19.271 mg.kg-1 and 11.30-13.29 mg.kg-1, which did not exceed the
standard compared with the background values of soil in Xinjiang. The ranges of
Cr, Hg, As contents were 80.29-85.42 mg.kg-1,0.06-0.07 mg.kg-1,30.64-31.52 mg.kg
1, all of which exceeded the standard compared with the background values of soil
in Xinjiang, and the exceeded rate was 60%. The values of PLI were in the order
of PLI0-10 cm(1.35) > PLI20-30 cm(1.28) > PLI10-20 cm(1.25), which belonged to
slightly polluted level. The values of HI were in the order of HI0-10 cm(2.53E
01) > HI20-30 cm(2.48E-01) > HI10-20 cm(2.43E-01), which indicated there was no
non-carcinogenic risk. The values of TCR were in the order of TCR0-10 cm(2.81E
05) > TCR20-30 cm(2.80E-05) > TCR10-20 cm(2.74E-05), which was the acceptable
level of carcinogenic risk. According to One -way ANOVA analyses, there was no
noticeable difference in the PLI, HI, TCR (alpha is 0.863, 0.134, 0.056
respectively). Geo-statistical Analysis results implied that the regions with
high contents of Zn, Cu and As were distributed near the coal industrial area and
Northern part of study area in the 0-10 cm soil layer, Pb formed V-shaped high
content ribbon, high content of Hg was located in the middle and Southern area,
and high content of Cr was located in Coal Industrial Area and the anterior
radial decline. High values of PLI, HI and TCR were found in north of the study
area. The moderate pollution region of PLI decreased with the increase of soil
depth, whereas HI and TCR showed no significant change. On the whole, high degree
of heavy metals pollution and high possibility of health risk were mainly
distributed around the six coal industrial areas which are in the high density
population zone. Especially, the pollution of Cr, Hg, As was relatively serious
and the health risk of As was the most serious which should be attached great
importance to.
PMID- 29965326
TI - [Characteristics of Microbial Nitrogen Degradation in Fluvo-aquic Soil of Hebei
Plain].
AB - Understanding the law of soil microbial degradation of nitrogen is of great
practical significance for the remediation of soil nitrogen pollution. From fluvo
aquic soil of Hebei plain, 8 kinds of bacteria,including nitrification bacteria,
ammonification bacteria, heterotrophic nitrification to aerobic denitrification
bacteria were isolated and analyzed by 16S rDNA identification, and the most
suitable strains were selected to prepare bacterial agents with optimized carrier
materials. The effects of the screened strains of bacteria or antagonistic fungus
to Chinese cabbage in the process of drip irrigation on nitrogen and PLFA
(Phospholipid Fatty Acids) values in the soils were discussed. The results showed
that by using diatomite as a carrier, the ammonia nitrogen degradation rate was
38% and the synthetic rate of nitrate was 205% with ammonibacteria, the synthetic
rate of ammonia nitrogen was 1711% with ammonibacteria, the degradation rate of
nitrate nitrogen was 367% with heterotrophic nitrification to aerobic
denitrification bacteria. In drip irrigation experiment, total nitrogen and
ammonia nitrogen in soil were better degraded and nitrification was stronger in
the soil, meanwhile, PLFA in the soil increased and content of microbes reached
the peak in shorter time, the soil biological environment was better after
irrigation with screened bacteria.
PMID- 29965327
TI - [Influence of Arsenate and Phenanthrene on Carbon-groups of Pteris vittata L.
Roots].
AB - To ascertain absorption of arsenate and phenanthrene as well as their influence
on carbon groups in excised roots of Pteris vittata L., the chemical structure of
the carbon groups in excised roots was characterized by solid state13C-Nuclear
Magnetic Resonance (13C-NMR). The results showed that the excised roots could
effectively absorb As and PHE without transpiration, and PHE promoted As
accumulation in the roots. Similarly, arsenate increased the adsorption of PHE by
the excised roots, the concentration of PHE was increased by 15%-53% compared
with CK. The carbon groups of the excised roots were dominated by O-alkyl C, the
percentage of carboxyl C was the lowest, mainly composed of carboxylic acids,
esters and amides. With the addition of As and PHE, the percentage of carboxyl C
increased significantly. The more stable and complex aromatic organic matter was
formed to improve the resistance and adaptability in excised roots of Pteris
vittata L. under As and PHE stress.
PMID- 29965328
TI - [Effect of Alkali Solids Amendment on Sewage Sludge Aerobic Composting and the
Potential of Related Products on Infertile Soil Amelioration].
AB - Aiming to evaluate the influence of alkali solids amendment on the sewage sludge
aerobic composting and to declare the potential of related composts on infertile
soil amelioration, sewage sludge and sawdust mixture were amended with straw
biochar, hardwood biochar, fly ash and lime by 10% addition ratio in dry weight
during the aerobic composting process; finally, potential of the related composts
on the infertile soil amelioration was investigated by pot experiment. The
results showed that the alkali solids amendment could prolong the thermophilic
phase, and promote the composting material heat inactivation. Addition of straw
and hardwood biochar facilitated more than 21.65% and 18.16% organic matter
degradation. During the composting, the compost pH decreased at the beginning and
then gradually increased before reached values of 6.78-7.33, while the fly ash
and lime amendments could lead to higher pH values in the beginning stage. The
alkali solids amendment reduced the salinity of the compost with final products
EC lower than 3000 MUS.cm-1. The addition of straw and hardwood biochar could
increase the total nitrogen content by reducing the ammonia loss at the
beginning, while the fly ash and lime amendments would result in ammonia loss in
the beginning stage. Despite the composting variation, the contents of nitrate
increased and the ammonium salt content decreased gradually. The biochar addition
can accelerate the nitrate transformation while the fly ash and lime amendment
had slight inhibitory effect on the nitrate transformation and plant germination.
The pot experiment revealed that applying compost products could significantly
improve the brassica growth, Cu and Zn micronutrients accumulation since the
compost addition could increase the soil organic carbon content, as well as soil
N, P, and K contents. Compared with the non-amended compost, the alkali solids
amendment could slightly reduce the Cu and Zn micronutrients accumulation, while
the fertile potentials were acceptable. The study indicated that straw and
hardwood biochar were more suitable than fly ash and lime as compost amendment,
and the related compost products had great potential on infertile soil
amelioration.
PMID- 29965329
TI - [Adsorption and Influential Factors of Diuron on the Loess Soil by Adding
Different Biochar Prepared at Varying Temperatures].
AB - The primary objective of this study was to investigate the effect of biochar,
produced from maize and pine needles residue at different temperatures, on the
adsorption of diuron onto loess soil. Meanwhile, the effect of the systemic
temperature, pH values and the initial concentration of diuron were also
investigated for the adsorption of diuron onto losses soil. And Kinetic
parameters, such as rate constants, equilibrium adsorption capacities and related
correlation coefficients were also calculated and discussed. The results showed
that the adsorption of diuron onto loess soil by adding biochar could be
described by the pseudo-second-order kinetic model, and followed the
intraparticle diffusion model, but diffusion was not only the rate-controlling
step. The adsorption process was divided into fast (0-8 h) and slow (8-12 h)
adsorption stages, and equilibrium was reached at around 12 h. The adsorption
thermodynamics of diuron onto loess soil was nonlinear by nature, and well fitted
with the Freundlich isothermal model. Thermodynamic parameter analysis of diuron
onto loess soil by adding biochar showed that Gibbs free energy (DeltaGtheta) was
less than zero, while Enthalpy (DeltaStheta) and Entropy (DeltaHtheta) were
greater than zero, indicating a spontaneous endothermic adsorption, which
increased the degree of disorder during the process. And Thermodynamic parameter
analysis of diuron onto loess soil without adding biochar showed that Gibbs free
energy (DeltaGtheta) and Entropy (DeltaHtheta) were less than zero, while
Enthalpy (DeltaStheta) was greater than zero. The average adsorption free energy
E was in range of 1.29-5.00 kJ.mol-1 when the temperatures increased from 25 to
45C, indicated that adsorption of diuron onto loess was a physical adsorption.
The results also suggested that the influencing factors of diuron had significant
effects on the adsorptive behaviors of diuron on loess soil. With increasing
pyrolysis temperature of biochar, the equilibrium concentration of diuron in
water decreased, while the amount of adsorption on loess soil increased. When the
initial concentration of diuron increased from 0.5 mg.L-1 to 6 mg.L-1, the
adsorption capacity of diuron onto loess soil by adding biochar showed a rapidly
increasing trend. When the initial concentration increased. the adsorption
capacity showed a slow increasing trend and gradually tended to be stable. In the
pH range of 3 to 10, the adsorption capacity of diuron onto loess soil by adding
biochar changed a little.
PMID- 29965330
TI - [Characteristics of Heavy Metal Contents in Human Hairs of Mine Contaminated
Areas in Nandan County].
AB - Nandan county is usually called "land of nonferrous metals". In order to discuss
the impact of mining activities on the health of inhabitants in Nandan county,
200 human hair samples were collected from 4 villages (Liuzhai is a
uncontaminated contrast areas, Chehe, Dachang and Zhanglao are contaminated
areas) of Nandan and analyzed for contents of As, Sb, Cd, Pb, Cu and Zn. The
results showed that the average contents of As, Sb, Cd and Pb were 1.260, 2.161,
2.466 and 20.92 MUg.g-1 in the human hair samples from contaminated areas. They
were 4.0, 20, 2.1 and 1.9 times higher than those in the contrast areas, and the
Sb contents in human hair of Chehe and Dachang were higher than the recommended
normal range. The contents of human hair Zn showed a negative correlation with
the age of people (P<0.05), and contents of human hair Cd and Pb showed a weak
negative correlation with the age of people in contaminated areas (P<0.1). The
independent-samples t-test showed that Cd contents in male hair were apparently
higher than those in female hair (P<0.05), however, Cu and Zn contents in female
hair were apparently higher than those in male hair (P<0.05), in the contaminated
areas. There were positive correlations between As and Sb, Cd and Pb, as well as
As and Cd (P<0.01), while other elements showed no significant correlation
between pairs. It was therefore concluded that contamination from the mining
activities has exposed a serious threat to human health in the mine contaminated
areas in Nandan county.
PMID- 29965331
TI - [Preparation of Mg-Al-Me(Me=La, Ce, Zr) Composite Oxides for Efficient Fluoride
Uptake].
AB - The Mg-Al-Me(Me=La, Ce, Zr) composites were prepared by co-precipitation method
of Mg, Al, Me(Me=La, Ce, Zr) salt solutions with a molar ratio of 20:1:4. The
sample were calcined at 500C for 5h as the adsorbents for removal of fluoride.
The adsorbents were characterized by scanning electron microscopy (SEM) and X-ray
diffraction (XRD). The patterns of SEM indicated that three calcined sorbents
were somewhat agglomerated particles to form a sheet structure after adsorption.
The patterns of XRD showed that the three adsorbents fored a metal composite
oxide. The effects of adsorption time, initial concentration of fluorine and
coexisting ions (Cl-, NO3-, SO42-, CO32-, HCO3-, PO43-) fluorine adsorption
properties on three adsorbents were tested by batch adsorption experiments. The
results showed that the kinetics of fluorine on three adsorbents were well fitted
by pseudo-second-order model. And the adsorption rate of fluoride on three
adsorbents decreased in the order of Mg-Al-Zr > Mg-Al-La > Mg-Al-Ce. Regression
results of adsorption rate controlling step test by moving boundary model
indicated that intra-particle diffusion rate was not the only rate-limiting step
in the adsorption of fluoride on the three materials. The equilibrium isotherm
showed that the adsorption capacity of fluoride uptake by three adsorbents
decreased in the order of Mg-Al-La > Mg-Al-Ce > Mg-Al-Zr. The adsorption isotherm
of three adsorbents was very well described by the Langmuir models, and their
linear correlations were 0.9958, 0.9790, 0.9975, respectively. The maximum
adsorption capacities of fluoride on Mg-Al-La, Mg-Al-Ce, Mg-Al-Zr calculated by
Langmuir model were as high as 54.22, 51.65, 50.89 mg.g-1, respectively. The
results showed that the co-existing anions such as CO32-, HCO3-, PO43- had an
inhibitory effect on the Mg-Al-La, Mg-Al-Ce, Mg-Al-Zr adsorption of fluoride. The
effect of coexisting anions on fluoride adsorption increased in the order of Cl-
< NO3- < SO42- < CO32-~HCO3- CO32- > SO42->=Cl-.
The phosphate-loaded FMCB could be effectively regenerated using NaOH solution
and repeatedly used. In column tests, about 800 bed volumes of simulated
groundwater containing 3 mg.L-1 were treated before breakthrough (phosphate
concentration in effluent reached 0.5 mg.L-1).
PMID- 29965333
TI - [Leaching Toxicity and Bioaccessibility of Heavy Metals in MSWI Fly Ash with
Various Particle Sizes].
AB - Size fractionation and chemical composition of municipal solid waste incinerator
(MSWI) fly ash were investigated. And the leaching efficiency of heavy metals was
contrastively studied using toxicity characteristic leaching procedure (TCLP),
European standard protocol (EN12457-2), sequential extraction procedure (SEP) and
physiologically based extraction test (PBET) for different size-fractionated fly
ash. The results indicated that the main compositing elements of fly ash were Ca,
Si, Al, Mg, Fe, Na, K. 58.7% of fly ash particles were in the range of 38-106 MUm
and the amount in the<150 MUm particle-size fraction accounted for more than 90%
of in total, Cu, Pb and Cd mainly existed in the residual form with a minor
amount of exchange fraction for any size-fractioned fly ash particles. TCLP
result showed that leaching amounts of Zn, Cu and Pb, except for As and V,
firstly increased and then decreased with the reduction of particle size. The
leaching amount of Zn reached the highest value of 547 mg.kg-1 in the range of 38
106 MUm, whereas the leaching amount of heavy metals exhibited a lower level for
all size-fractioned fly ash particles. The extraction concentrations of Zn, Pb,
Cu and As reached 3270, 339, 335 and 16.8 mg.kg-1 for the PBET tests,
respectively, which were significantly higher than those of the TCLP. Therefore,
heavy metals in MSWI fly ash had the potential bioavailability to human body.
PMID- 29965334
TI - [Comparison of Models on Spatial Variation of PM2.5 Concentration:A Case of
Beijing-Tianjin-Hebei Region].
AB - Due to the rapid urbanization and increasing energy consumption, air pollution,
especially some fine particulates like PM2.5 rise in the context of fast
urbanization. PM2.5 pollution has been given considerable attention recent years.
High PM2.5 concentration is the main reason for the atmospheric haze in Beijing
Tianjin-Hebei region. Air pollution has become the key issue restricting the
sustainable development of Beijing-Tianjin-Hebei region and even the whole
country. Long-term exposure to PM2.5 is likely to cause adverse effects on human
health. The spatial-temporal variation of air pollution can be characterized by
the land use regression model. It is significant to have a good knowledge of
spatial characteristics of PM2.5 concentration, which could assist air pollution
management and the epidemiological research. This manuscript used air quality
data of 104 monitoring sites of Beijing-Tianjin-Hebei region from 1st January
2014 to 31st December, 2014, combined with VIIRS (visible infrared imaging
radiometer) AOD(aerosol optical depth), land use, meteorological factors, road
network, population, and pollutant sources distribution to establish the land use
regression model by least square method and geographically weighted method
respectively. The four models established were least square land use regression
model with VIIRS AOD data, geographically weighted land use regression model with
VIIRS AOD data, least square land use regression model without VIIRS AOD data and
geographically weighted land use regression model without VIIRS AOD data. And the
adjusted R2 values for these four models were 82.13%, 84.87%, 80.45% and 81.99%,
respectively. Research results demonstrated that the geographically weighted
method performed better than the least square method and improved the land use
regression model to a certain extent.
PMID- 29965335
TI - [Change of Atmospheric Pollution Diffusion Conditions in Beijing in Recent 35
Years].
AB - In this paper, the monthly average of NCEP(National Center for Environmental
Prediction)reanalysis data (2.5 degrees *2.5 degrees ),the sounding data, and
conventional observation data in Beijing (54511 station) were used to analyze the
atmospheric pollution diffusion conditions in Beijing in recent 35 years. The
main conclusions were:in 1980~2015, the whole layer was warmer. After 1990, the
temperature inversion phenomenon was obvious, and the whole air was stable. The
cold air's less effect on the lower layer, lower frequency of great north wind
speed and surface layer's convergence led to the rising of pollution
concentration. The location of sink motion at the high level was lower and that
of the ascending motion at the low level was higher. This led to the constriction
of the ascending motion below the boundary layer, worsening the pollution
diffusion condition. In 1980~1989, the atmospheric capacity index was steady,
while in 1990-1999,it fluctuated obviously and after 2000,it declined. In
general, the atmospheric capacity presented a gentle decline. In spring and
winter of 1980-1989, as well as spring and summer of 1990-2015, the atmospheric
capacity was better. After 2000, the atmospheric capacity was decreasing compared
to the last 20 years no matter in which season, and the difference of atmospheric
capacity in seasons diminished. The boundary layer was higher in spring and
summer, and lower in fall and winter in recent 35 years.
PMID- 29965336
TI - [Precipitation and Its Effects on Atmospheric Pollutants in a Representative
Region of Beijing in Summer].
AB - Atmospheric precipitation samples were collected in a representative region of
Beijing in summer of 2015 to investigate the physical and chemical
characteristics of atmospheric precipitation, the changes and causes of major
chemical components in rainwater during the course of typical precipitation, and
the impacts of typical precipitation processes on atmospheric pollutants. The
volume-weighted mean pH value of rainwater in the representative region of
Beijing in summer was 6.21 with the range of 5.15-7.34,and acid rain seldom
occurred. The pollution elements Cd, Ca and Mn were moderately enriched, and Cu,
Zn, Pb and S were seriously enriched in rainwater, of which Ca and S were main
pollution elements, which accounted for 45.43% and 43.93% of the total pollution
elements respectively, and Zn, Mn, Cu, Pb and Cd were main heavy metal pollution
elements, which accounted for 1.32% of the total pollution elements. Different
rates of precipitations could have different impacts on atmospheric pollutants.
PM2.5 could be scavenged by raindrop, and SO2, NO2 and O3 could be scavenged
greatly by raindrop during the precipitation episode at a relatively high
rainfall rate, containing four significant stages, such as clear-out of
atmospheric pollutants, accumulation, both accumulation and clear-out, and
another clear-out of airborne pollutants. Atmospheric pollutants such as PM2.5,
SO2, NO2 and O3 could mainly be scavenged by in-cloud scavenging processes during
the precipitation episode at a relatively low rainfall rate, including four
important stages, such as clear-out, both clear-out and accumulation,
accumulation, and another clear-out of atmospheric pollutants. The effect of
rainfall at a relatively high rate on atmospheric pollutants was bigger than that
of rainfall at a relatively low rate.
PMID- 29965337
TI - [Impact of Mountain-Valley Wind Circulation on Typical Cases of Air Pollution in
Beijing].
AB - The impact of mountain-valley wind circulation on the typical examples of
pollution was analyzed through the selected pollution process, combining with the
hourly PM2.5 concentrations and meteorological data in Haidian, Shangdianzi and
Lishuiqiao in Autumn and Winter from 2013 to 2015, and also the data of Tower of
atmospheric, wind profile of Haidian and automatic meteorological stations in the
same period. The analysis showed that the average wind speed of valley wind was
greater than that of the mountain wind, and they both would be "broken" during
the conversion time in the mountain-valley wind days. In contrast with the
mountain wind, the average duration of valley wind in autumn was longer than that
in winter, and the start time of valley wind in autumn was earlier than the same
wind in winter; influenced by the topography of Beijing area, the direction
boundary of the transformation between mountain-valley wind was northeast
southwest. The frontier of mountain wind in autumn could fall down to the South
Second Ring Road, and it could be pressed to the South Third Ring Road in winter;
the average thickness of valley wind was greater than the mountain wind. Whether
the moment was in autumn or winter, in the south, the average time when the PM2.5
concentration began to rise, was earlier than in the north in a day; the time
when concentration of pollutants began to rise in the fall was earlier than in
the winter, but the time when the concentration began to decline showed the
opposite trend. The transition zone of different PM2.5 concentration in Beijing
in autumn or winter located in South Second Ring Road (South Third Ring Road),
and it would move to south over time. Duration autumn and winter seasons, this
phenomenon lasted about 4 and 2 hours, respectively. Furthermore, the positive
and negative feedback effects may exist between pollutant concentrations and
mountain-valley wind.
PMID- 29965338
TI - [Fugitive Dust Emission Characteristics from Building Construction Sites of
Beijing].
AB - Particulate matter (PM) is the primary air pollutant in Beijing, and its emission
control is an important direction of air pollution prevention and control.
Construction dust plays a significant role in the source of airborne particulate
matter in Beijing. Due to population growth and economic development, the demand
for residential and office space has been increasing which results in a high
construction area in Beijing and dust pollution caused by construction
activities. However, there are few studies focusing on fugitive dust emissions
from construction sites and their contribution to air pollution in Beijing. Under
this background, this paper established an estimation model of dust emission from
construction sites, and used the localized emission factor to calculate the dust
emission from 2000 to 2015 in Beijing, identified the emission characteristics
and laws of construction dust emission and quantified the uncertainty range of
the emissions. The WRF/CMAQ model system was used to simulate the contribution of
dust pollution to quantify its influence on air quality. The results showed that
the dust emission from construction sites in Beijing has been increasing, but the
construction area is falling in recent years. However, the emission of PM is
still high and needs to be paid enough attention. In the spatial distribution,
the dust emissions in summer and autumn are larger than those in other seasons.
As for spatial distribution, the construction dust is mainly concentrated in the
urban function extension area and suburban area, which is related to the
extension of population activities and the gradual development of urbanization.
The contribution of construction dust to PM10 and PM2.5 concentration in the
ambient air can reach 31.3 MUg.m-3 and 9.6 MUg.m-3, respectively. Through
scenarios analysis, for further reduction of the emission from construction sites
in 2030, more stricter standard for green construction and powerful supervision
are needed.
PMID- 29965339
TI - [Characteristics of Volatile Organic Compounds Emitted from Biomass-pellets-fired
Boilers].
AB - A pre-concentrator-GC-MS/FID was used to investigate the characteristics of
volatile organic compounds (VOCs) based on the flue gases emitted from five
biomass-pellets-fired boilers in this study. And the concentrations of particle
matter, nitrogen oxides (NOx), sulfur dioxides (SO2) and mercury and its
compounds were also measured. Results demonstrated that the concentrations of SO2
and mercury and its compounds emitted from all five boilers were relatively low,
which were lower than the national emission standard, while NOx and particles
from some boilers were higher than the standard. The mass concentration of 56 VOC
species was in the range of (872.43+/-293.80)-(6929.66+/-1137.25) MUg.m-3, and
the analysis of influencing factors implied that the furnace temperatures and
loads havd strong negative correlations with the concentration of total VOCs. The
emission components of VOCs were mainly composed of alkenes (41%-59%) including
ethylene, 1-butene, cis-2-butene and 1-hexene; alkanes (27%-49%) including
hexane, isopentane and cyclopentane; and aromatics (6%-18%) including benzene and
toluene. Moreover, the maximum incremental reactivity (MIR) method was applied to
analyze ozone formation potential (OFP) of VOCs. The contribution of OFP of five
boilers was mainly from alkenes, occupying a relatively high percentage of 76%
90%, and that of alkanes was in the range of 6% to 19%.
PMID- 29965340
TI - [Effect of VOCs on O3 and SOA Formation Potential During the Combined Pollution
Process in Guangzhou Panyu Atmospheric Composition Station].
AB - An analysis was made by using historical observational data of Guangzhou Panyu
Atmospheric Composition Station(GPACS). The results showed that typical haze
processes accompanied with high ozone episodes happened during the period from
September 2rd, 2011 to September 5th, 2011(P1) and the period from June 12th,
2012 to June 15th, 2012(P2) respectively. During the two combined pollution
processes (P1 and P2), daily visibility ranged from 5.78 km to 6.91 km and from
5.60 km to 9.25 km, and the maximum 8 h O3reached 92.14*10-9 and 91.29*10-9
respectively. Among the 55 detected volatile organic compounds(VOCs), alkenes and
aromatics had the highest reactivity with the 41%, 39% proportions of equivalent
propylene concentration and the proportions of 28%, 54% in the aspect of ozone
formation potential during P1. Alkenes and aromatics contributed 35% and 46% of
equivalent propylene concentration, as well as 22% and 61% to ozone formation
potential during P2. In terms of SOA formation potential by FAC estimation,
alkanes, alkenes and aromatics accounted for 13.2%, 21.4%, 65.4% during P1 and
4.6%, 13.8%, 81.6% during P2 respectively. Toluene, isoprene, ethylbenzene and
m,p-Xylene had large contributions to the ozone and SOA formation. Factors
including pollutants transported from the downtown area, continuous gentle wind,
high temperature, low humidity and strong radiation gave rise to the occurrence
of high ozone episodes in these two haze processes.
PMID- 29965341
TI - [Characteristic Study on the "Weekend Effect" of Atmospheric O3 in Northern
Suburb of Nanjing].
AB - The data of ozone (O3) and its precursors (NOx, CO, VOCs) observed at northern
suburb of Nanjing from December 01, 2013 to November 30, 2014 were used to
analyze the difference of pollutant concentrations on weekends and weekdays, and
its causes. The results showed that there was an obvious "Weekend Effect" in
northern suburb of Nanjing. The mass concentrations of O3 on weekdays were higher
than those on weekends, whereas mass concentrations of its precursors were higher
on the weekends; The average mass concentrations of O3 were 19.84 MUg.m-3, 53.45
MUg.m-3, 57.17 MUg.m-3, and 40.43 MUg.m-3 in winter, spring, summer, and autumn
respectively. Compared with other seasons, "Weekend Effect " was more distinct in
spring. The value of NO2/NO was 4.81% higher on weekdays (3.63) than on weekends
(3.46). The longer cumulative time and higher accumulation rate of O3, and the
stronger atmospheric oxidation capacity on weekdays were responsible for the
higher O3 mass concentrations on weekdays. The correlation coefficients of the
mass concentrations of O3 with VOCs, NOx, NO, and NO2 were higher on weekdays
than on weekends.
PMID- 29965342
TI - [Atmospheric Ammonia/Ammonium-nitrogen Concentrations and Wet and Dry Deposition
Rates in a Double Rice Region in Subtropical China].
AB - Ammonia (NH3) is the most abundant alkaline gas in the ambient air, and it is
also one of the important precursors for the ammonium salts in aerosol and
rainwater. Though the emission intensities of NH3 and acidic gases are high, the
concentrations and deposition rates of atmospheric ammonia-nitrogen (NH3-N),
particulate ammonium-nitrogen (NH4+-Np) and rainwater ammonium-nitrogen (NH4+-Nr)
in double rice regions in subtropical China are still less known. In this study,
atmospheric concentrations of NH3-N, NH4+-Np in PM10 and NH4+-Nr and related
meteorological parameters were observed simultaneously in a typical double rice
region in the subtropical hilly region of China, with the aim to clarify the
characteristics and influencing factors of atmospheric NH3/NH4+-N concentrations
and to quantify the wet and dry deposition rates of atmospheric NH3/NH4+-N. The
results showed that the annual mean concentrations of nitrogen in NH3-N, NH4+-Np
and NH4+-Nr were 5.7 MUg.m-3, 12.8 MUg.m-3 and 0.8 mg.L-1, respectively, and
their deposition rates were 8.38, 5.61 and 9.07 kg.(hm2.a)-1, respectively. The
NH3-N concentration was significantly increased after application of nitrogen
fertilizer in the paddy field, and had a significant positive correlation with
the air temperature. The NH4+-Np concentration did not show significant
correlation with NH3-N concentration, indicating that atmospheric NH3-N
concentration was not the main limiting factor for the NH4+-Np pollution in the
studied region. The NH4+-Nr concentration was positively correlated with the NH4+
Np concentration but negatively correlated with precipitation. The high
concentrations and deposition rates of atmospheric NH3-N/NH4+-N in the studied
region indicated that the atmospheric NH3/NH4+-N pollution was serious, and
atmospheric deposition of NH3/NH4+-N was an important nitrogen source in paddy
fields, which should be considered in cropland nitrogen nutrient management.
PMID- 29965343
TI - [Species of Iron in Size-resolved Particle Emitted from Xuanwei Coal Combustion
and Their Oxidative Potential].
AB - Many reports have claimed that high lung cancer mortality rate in Xuanwei is
associated with the residential coal combustion. Considering iron is the main
chemical element in the particles emitted from Xuanwei coal combustion, and
especially, reactive oxygen species (ROS) could be generated by redox-active
transition metals (TM) such as iron (Fe) in particles, therefore, raw coal
samples from 4 coal mines in Xuanwei were sampled, and size-resolved particles
emitted from the raw coal samples were collected by using of Andersen Five-stage
High Volume Sampler. Species of iron in the raw coal sample, size-resolved
particles and bottom ashes were analyzed by BCR sequential extraction method
(community bureau of reference, BCR). The generation potential of.OH free
radicals from coal emission particles in the surrogate lung fluid (SLF) solution
was measured by using high pressure liquid chromatography (HPLC). Our results
demonstrated that a large fraction of oxidizable Fe could be found in raw coal
samples. However, the acid extractable, reducible and oxidizable fractions of Fe
in the fly ash particles accounted for a large proportion (46%-78%) in the size
resolved particles after coal combustion. There was difference in levels of.OH
free radicals generated from coal emission particles in the SLF for 24 hours
among particles with different sizes. The concentration of.OH increased in both
fine particles (<1 MUm, 1.1-2 MUm, 2-3.3 MUm) and coarse particles (3.3-7 MUm, >7
MUm) as the particles size decreased. Linear correlation could be found between
the oxidizable fractions of iron and the generation of.OH in particles emitted
from coal combustion (R2=0.32).
PMID- 29965344
TI - [Dioxin Pollution and Occupational Inhalation Exposure of PCDD/Fs in Municipal
Solid Waste Incinerator].
AB - To assess the pollution levels, characteristics, and the pollution sources and
occupational inhalation exposure of polychlorinated dibenzo-p-dioxins and
dibenzofurans(PCDD/Fs)in the workshops,ambient air samples in different types of
incinerators of two municipal solid waste incinerators(MSWI) were collected and
analyzed. The results showed that 1 The I-TEQ concentration ranged from 0.034
2.152 pg.m-3in the two waste incineration plants, and the most sites' I-TEQ
exceeded the ambient air quality standard. Besides, the I-TEQ concentration
behind the incineration plant was higher than others. 2 The dioxins in
incineration plant were dominated by OCDD and 1,2,3,4,6,7,8-HpCDD. For MSWI A,
the flue gas and the fly ash had major effect on PCDD/Fs, while the dioxins
pollution in MSWI B was only affected by the fly ash. 3 Occupational inhalation
exposure of PCDD/Fs was 0.01-1.10 pg.(kg.d)-1 in incineration plant, some
occupational inhalation exposure values exceeded the evaluation standard, and the
areas behind the incinerators were evaluated to have a high exposure risk.
PMID- 29965345
TI - [Characteristics of Mercury Emissions from Modern Dry Processing Cement Plants in
Chongqing].
AB - Three typical modern dry processing cement plants in Chongqing were chosen to
investigate mercury emission characteristics and its source and fate through a
mercury mass balance method by analyzing mercury contents in all input and output
materials. The results showed that limestone was the main source of mercury in
three cement plants followed by coal, and their mercury concentrations were
(0.025+/-0.001)-(0.032+/-0.002) mg.kg-1and (0.080+/-0.002)-(0.110+/-0.012) mg.kg
1, respectively. The highest mercury level in all required input materials was
(0.447+/-0.007)-(0.525+/-0.009) mg.kg-1 for gypsum, while the mercury content of
other raw materials were very low. Most of the mercury released from these cement
plants entered into flue gas, and the mercury of gypsum entered into cement. The
mercury emission fluxes were calculated to be (73.42+/-8.10)-(215.18+/-10.75) g.d
1 in these three selected plants. The mercury emission factors for clinke and
cement (EFclinker and EFcement) were (0.016+/-0.001)-(0.049+/-0.001) g.t-1 and
(0.011+/-0.000)-(0.036+/-0.001) g.t-1, respectively, which were significantly
lower than that employed in cement industry according to the foreign mercury
emission factors in the past.
PMID- 29965346
TI - [Correlations of Light-duty Gasoline Vehicle Emissions Based on VMAS and CVS
Measurement Systems].
AB - Gaseous emissions from 25 State 2-5 light-duty gasoline vehicles were tested by
Vehicle Mass Analysis System (VMAS) and CVS (Constant Volume Sampling) system,
respectively. The correlations of emission factors of tested vehicles measured by
these 2 methods were analyzed. The results showed that emission factors of light
duty gasoline vehicle had a decreasing trend with the promotion of emission
standard. There were some high-emitting vehicles in the fleet of tested State 2
and State 3 vehicles, but fewer in State 4 or Stated 5 vehicle fleet. The
correlations of the emission factors measured by the 2 methods deteriorated with
the promotion of emission standard. The relative bias of CO and HC+NOx emission
factors measured by the 2 methods reached 197% and 177%, respectively. The
correlation coefficient of emission factors of higher-emitting vehicles was 0.75
0.85, while that of lower-emitting vehicles was only 0.46. If tighter emission
standard of in-use light-duty gasoline vehicle was adopted, the false positive
rate of measurement results by VMAS would rise significantly. In summary, VMAS
method is hard to be applied in the emission measurements of light-duty gasoline
vehicles with stricter emissions standard. It is necessary to conduct more
studies on sophisticated in-use vehicle measurement system.
PMID- 29965347
TI - [Emission Characteristics of Particulate Matter from Diesel Buses Meeting
Different China Emission Standards Fueled with Biodiesel].
AB - Based on heavy chassis dynamometer, an experimental study was conducted in diesel
buses compliant with China III,IV,V emissions standards respectively, fueled with
three different blends of petroleum diesel/biodiesel (0%,5%and 10%, V/V biodiesel
blends), which investigated the characteristics of particulate matter (PM)
emission under CCBC driving cycle. Results of study showed that the total PM
number and mass emission from China V bus respectively decreased by
68.1%,56.2%,57.5% and 52.7%,64.8%, 88.5% compared to China III bus. When compared
to China IV bus, the PM mass emission decreased by 43.0%, 47.3% and 42.1%, while
the number increased by 4.0%,7.6% and 14.7%. The nucleation mode PM emission of
China III bus was mainly from high-speed driving condition, while China IV and V
buses were from middle-low speed. The accumulation mode PM emissions of China
III, IV and V buses were all mainly from middle-low speed driving conditions. In
relatively lower speed conditions, compared to China III bus, the nucleation mode
PM emissions of China IV and V buses obviously decreased, so was accumulation
mode PM. Compared to China IV bus, emission of China V bus did not improve
obviously and the nucleation mode PM emission even increased. In high-speed
driving condition, the nucleation mode PM emission from China III bus increased
dramatically, while those from China V and IV buses slightly increased.
Meanwhile, the accumulation PM number and mass emission of China IV bus was
obviously higher than those of China V and III buses. When fueled with B10, the
relatively bigger sizes PM emission of China III bus deteriorated rapidly,
indicating that China III bus was not suitable for fuel with high blending ratio
of biodiesel.
PMID- 29965348
TI - [Spatial Variation and Environmental Significance of delta18O and deltaD Isotope
Composition in Xijiang River].
AB - The H and O isotope composition of the Xijiang water was investigated on 54
samples collected from the mainstreams and main tributaries in June 2014 and
January 2015.It was found that in the Xijiang river, there was a remarkable
linear relationship between delta18 O and deltaD. This relationship was more
significant in the dry season. In both seasons, the 18 O and D values distributed
along the meteoric water line, which indicated that precipitation was the source
of the Xijiang River. Due to the direct water recharge through karst forms (i.e.
sinkholes, vertical shaft and funnel) to the underground river, the d-excess
value was higher in the rainy season. While during the dry season, water recharge
came from the storage in fissures and pores. Affected by altitude and evaporation
effect, along the mainstream Hongshui River-Xunjiang and tributary Youjiang
Yujiang reach, the delta18 O and deltaD values were gradually approaching
positive value in general. However, along the short tributary Guijiang reach, the
altitude difference was not dramatic, and the discharge was less, the same
phenomenon was not observed. By establishing a linear regression model between
delta18 O and altitude, it revealed that the change rate of Xijiang water with
altitude was -0.440/00.(100 m)-1 in the rainy season, and -0.450/00.(100 m)-1 in
the dry season. The result reflected the height effect of the precipitation,
which has a considerable meaning for the study of hydrological cycle in a river
basin.
PMID- 29965349
TI - [Comparative Study of SWAT and DNDC Applied to N Leach and Export from
Subtropical Watershed].
AB - In this study, N export from Xiangxi River Basin in subtropical watershed was
measured by long-term monitoring, N loss in the basin was simulated by DNDC and
SWAT models in order to provide a scientific basis for the establishment of
nitrogen circulation model in subtropical watershed. The results showed that N
loss with runoff was well simulated by DNDC and SWAT. The key parameters of DNDC
were precipitation, slope and amount of N fertilization, while the key parameters
of SWAT were GW_DELAY, CANMX, ALPHA_BF and ESCO. The deviations between
simulations and observations of runoff, TN and NO3--N simulated by DNDC were
5.19%, 8.10% and 71.70%, respectively. Whereas the deviations between the
emission of TN, NO3--N and NH4+-N simulated by SWAT and observations were 2.04%,
14.29% and 8.89%. The results indicated that the precision of N export simulated
by SWAT was higher than DNDC in Xiangxi River Basin, and N loss in this area was
mainly controlled by precipitation and nitrogen cycle of terrestrial ecosystem.
The temporal and spatial distribution of N loss in Xiangxi River Basin was
analyzed by comparing simulation results, which further demonstrated that DNDC
and SWAT had simulation ability for N loss in subtropical watershed.
PMID- 29965350
TI - [Comparison of Relationship Between Conduction and Algal Bloom in Pengxi River
and Modao River in Three Gorges Reservoir].
AB - Pengxi River is the largest tributary in the northern bank of Yangtze River in
the Three Gorges Reservoir (TGR) region, and serious algal bloom has been
reported since 2003 when the TGR dam started impounding water. On the other hand,
Modao River, a tributary in TGR locating in the same county with Pengxi River,
was rarely reported with algal bloom in the same time period. In this study,
water samples were collected on the same day in both rivers in spring and summer,
the most likely blooming seasons in TGR, to compare the water quality parameters
and Chlorophyll-a(Chl-a) concentration dynamics in order to understand the
mechanism of algal bloom in TGR. The results showed that the maximum value of Chl
a in Pengxi river reached 60.5 MUg.L-1 in spring, and was only 7.8 MUg.L-1 in
summer, while in Modao river the Chl-a content was 2.92 MUg.L-1 in spring and
7.48 MUg.L-1in summer. Both rivers stratified during samplings, but having layers
of thermocline and hypolimnion with the lack of epilimnion, and most of Chl-a
content was located in thermocline. Also in both rivers, TN and TP exceeded the
international threshold for eutrophication, with the average TN and TP values of
2.305 mg.L-1 and 0.053 mg.L-1in Pengxi River in spring, and 1.673 mg.L-1 and
0.097 mg.L-1 in summer, respectively, while in Modao River the values were 1.875
mg.L-1 and 0.075 mg.L-1 in spring, and 1.79 mg.L-1 and 0.054 mg.L-1 in summer
respectively. Nutrients concentrations showed no significant correlation with Chl
a. On the other hand, conductivity value and trend were totally different between
the two rivers:in Modao River in spring, the conductivity in upstream was only
75% of that in the main stream of the Yangtze River, and the backwater from the
main stream reached to the middle in Modao river, where the highest Chl-a among
all the river sampling sites was detected; summer conductivity distribution was
similar with that in spring. Different from Modao River, the conductivity in
upstream of Pengxi River in spring was 150% of that in the main stream of
Yangtze, the backwater from the main stream reached area between sampling sites
of PX04 and PX05 (upper than the middle reach); its upstream had significantly
high content of Chl-a and conductivity, and these two factors were significantly
positively correlated. The study showed that other than N and P, other ions in
the Pengxi River played an important role in bursting "bloom", and need to be
considered regarding bloom control.
PMID- 29965351
TI - [Temporal and Spatial Variation Characteristics of Nitrogen and Phosphorus in
Sediment Pore Water and Overlying Water of Dianchi Caohai Lake].
AB - The vertical variation in the contents of nitrogen and phosphorus with different
forms in pore water and overlying water was continuously measured for twelve
months in Dianchi Caohai Lake. The research revealed the difference of N or P
concentration between pore water and overlying water and the contribution of
nitrogen and phosphorus forms. It is significant to understand the formation of N
and P and the ratio of N/P in pore water in the fields of lake eutrophication and
the control of internal nutrient-loading. The results demonstrated that:1Sediment
pore water rho(NH4+-N) was significantly higher than that in overlying water. But
for NO3--N, it obeyed the opposite rule. From Feb. to Nov., rho(SRP) was higher
than that in overlying water, while the opposite rule was found in Dec. and Jan..
2In sediment pore water, rho(NH4+-N) or rho(SRP) presented the maximum
contribution ratio of DTN (78%) or DTP (61%), respectively. While, in overlying
water, the maximum contribution ratio was DON(44%) or DOP(81%), respectively.
Compared to those in spring and winter, the contribution of rho(NH4+-N) and
rho(SRP) increased distinctly and the contribution of rho(NO3--N), rho(DON) and
rho(DOP) dropped obviously in summer and autumn. 3The temporal variations for the
ratios of DTN/DTP, (NH4+-N+NO3--N)/SRP and DON/DOP in pore water were all in the
following sequence:spring> winter> summer> autumn. In overlying water, the N/P
ratio in spring was relatively higher than that in the other three seasons.
PMID- 29965352
TI - [Distribution and Emission Flux Estimation of Phosphorus in the Sediment and
Interstitial Water of Xiangxi River].
AB - The distribution and vertical variation of phosphorus forms in sediments along
Xiangxi River were analyzed with Hedley classification method, meanwhile the
influences of physical and chemical properties of overlying and interstitial
water on the release of phosphorus in sediment were discussed. The major findings
showed that the pH values in the overlying and interstitial water increased from
4.72 to 8.55, and were slightly acidic in summer, while weak alkaline in other
seasons. The redox potential of sediment was in the reduction state overall. The
annual variation range of total phosphorus (TP) content in the overlying and
interstitial water, and that in the sediment was 0.02-0.48 mg.L-1 and 0.48-1.45
g.kg-1, respectively. The distribution features of TP content in the sediment
were the same with those in the interstitial water along the Xiangxi River. It
was interesting that the content of TP in the interstitial water in spring and
summer was higher than that in autumn and winter, but that in the sediment of
Xiangxi River was opposite. The content of different phosphorus (P) forms
decreased successively:HCl-P (HCl extracted phosphorus)> Res-P (residual
phosphorus)> NaOH-P (NaOH extracted phosphorus)> NaHCO3-P (NaHCO3 extracted
phosphorus)> H2O-P (water-soluable phosphorus). The reductive environment of the
interface between sediment and overlying water, and pH of water in spring (weak
alkaline) and summer (slightly acidic), were conducive to phosphorus release from
sediment into overlying water, increasing the eutrophication risk. TP content in
the interstitial water was closely related to that in sediment. The PO43--P in 4
sampling areas diffused from the interstitial water into the overlying water with
diffusive fluxes in the range of 0.01-0.04 mg.(m2.d)-1. All of these findings
indicated that sediments is an important source of nutrient for the overlying
water.
PMID- 29965353
TI - [Pollution Characteristics and Risk Assessment of Heavy Metals in Water and
Sediment from Daye Lake].
AB - The surface water and surface sediments were collected from Daye Lake in April
2014. The concentrations of heavy metals were determined by atomic absorption
spectroscopy. The pollution potential health risk and ecological risk of heavy
metals in water and sediment were assessed by the health risk assessment model
and the potential ecological risk index method. The results showed that the
concentrations of the heavy metals (Ni, Cd, Cu and Pb) was 49.27 MUg.L-1, 2.19
MUg.L-1, 12.18 MUg.L-1, 12.13 MUg.L-1(water) and 78.46 mg.kg-1, 77.13 mg.kg-1,
650.13 mg.kg-1 and 134.22 mg.kg-1 (sediment). Enrichment coefficient indicated
that the enrichment of Cd, Cu and Pb was more serious, especially the
accumulation of Cd was the most obvious. Compared to typical lakes in China, the
contents of heavy metals in water and sediment were relatively high. The spatial
pollutant distribution of the heavy metals in water and sediment all presented
that the concentrations of the heavy metals were relatively higher in east and
west of Daye Lake, relatively more uniform in the middle, and their origins were
mainly from human activities. The results of environmental risk indicated that
the carcinogens and chemical non-carcinogens health risk values of heavy metals
by drinking water pathway were 9.77E-08~1.63E-05a-1. Therefore, the pollution of
Ni and Cd should be the primary control target for environmental health risk
management. The descending order of pollution degree of four metals in sediment
was Cd> Cu> Pb> Ni, and Cd was the main contributor of the potential ecological
risk elements.
PMID- 29965354
TI - [Formation of Brominated Disinfection By-products in Low Temperature Multi-effect
Distillation (LT-MED) Process for Seawater Desalination].
AB - Changes in water quality and brominated disinfection by-products (Br-DBPs) during
a low temperature multi-effect distillation (LT-MED) process for seawater
desalination were investigated. The concentrations of bromide ion and specific
ultraviolet absorbance (SUVA) in the seawater (i.e. the influent of LT-MED) were
54.6 mg.L-1 and 1.7 L.(mg.m)-1, respectively. The tryptophan-like aromatic
protein, fulvic acid-like and soluble microbial by-product-like organics
dominated the fluorescent dissolved organic matter (DOM) in the seawater. After
the NaClO pre-chlorination in the LT-MED process, the concentrations of DBPs in
the seawater were significantly increased, especially Br-DBPs, and
Bromoform(CHBr3) accounted for 100% of total trihalomethanes (THMs), Bromoacetic
acid (C2H3BrO2) and dibromoacetic acid (C2H2Br2O2) accounted for 31.9% and 68.1%,
respectively of total haloacetic acids (HAAs), while 4-Bromophenol (C6H5BrO)
accounted for 100% of total halogenated phenols (HPs). The formation of THMs,
HAAs and HPs was not detected in the finishing water produced by the LT-MED
desalination process, but these substances were retained in the concentrated
brine, of which THMs, HAAs and HPs were 56.9, 35.0 and 0.1 MUg.L-1.
PMID- 29965355
TI - [Applicability Comparison and Application Study of Two Methods for Determination
of the Copper Complexing Capacity of Waters].
AB - Complexing capacity (CC) is an important indicator affecting the environmental
behavior of heavy metals in water, which can be determined by different methods
based on different mechanisms. To validate and compare the applicability of
different methods in CC determination, the complexing capacity of Cu2+ (CuCC) in
solutions of ethylenediamine tetraacetic acid (EDTA) and acesulfame was
determined by methods of dithizone extraction kinetics (DEK) and ion-selective
electrodes (ISE), while EDTA and acesulfame were selected to represent strong and
weak ligands in water, respectively. DEK method was found to be more suitable for
determining the contribution of strong ligands to CuCC, while the results
determined by ISE were related to both the strong and weak ligands in water. DEK
and ISE methods were used to measure CuCC of several actual water samples,
including samples from reservoir, discharge river, fishpond, and landfill
leachates. CuCC in the water samples of the reservoir and discharge river
measured by ISE were 86.9-227.0 MUmol.L-1, which were about one order of
magnitude higher than those measured by DEK (9.9-14.6 MUmol.L-1). For the
landfill leachates, CuCC measured by ISE were 6998.4-31005.8 MUmol.L-1, which
were 2 orders of magnitude higher than those by DEK (89.6-109.1 MUmol.L-1). The
increase of CuCC in the polluted water samples might be due to the weak ligands
like pollutants. A positive correlation (R=0.975, P<0.01) was found between the
CuCC related to the weak ligands (DeltaCuCC) and the sum concentration of ammonia
nitrogen and organic nitrogen in waters.
PMID- 29965356
TI - [Performance of Applying Scale Permeable Pavements for Control of Runoff
Pollution in an Area with High Groundwater Level].
AB - The purpose of this article was to study the effect of permeable pavements on
runoff pollution control and its possible influence on groundwater quality in the
area with high groundwater level. Three experimental permeable parking lots and
one impermeable parking lot were built in urban Shanghai in order to monitor
their quality of influent and effluent water under actual precipitation
conditions, in order to investigate the performance of pollutant control effects
and to evaluate the possibility of the pollution of groundwater. The results
showed that all the three facilities could effectively remove TP, TSS, COD, Cr,
Mn, Cu, Zn, Pb and O&G, but imposed poor removal efficiency on TN. Obvious
release of NO3--N occurred in all three pavements. The permeable interlocking
concrete pavement using cement stabilized crushed stones as base course and the
one using crushed stones as base course had a better removal efficiency on NH4+-N
than the previous concrete one. The quality of effluent water from different
permeable pavements had no significant difference except NH4+-N. The in-situ
groundwater quality was generally worse than background values of groundwater in
Shanghai. Effluent water quality of three permeable pavements was generally worse
than that of the in-situ groundwater, and a number of indicators belonged to or
were close to groundwater class V standard. In the area with high groundwater
level, there was risk of groundwater pollution caused by permeable pavements
without liners.
PMID- 29965357
TI - [Removal of 2,4-dichlorophenol in Underground Water by Stabilized Nano Zero
valent Iron].
AB - To restrain the nano zero-valent iron (NZVI) in aqueous solution from being
reunited and oxidized, this paper used sodium carboxymethyl starch (CMS), which
is an environmentally friendly and cheap material, for coating and surface
modification of NZVI so as to improve its dispersity and suspension property.
Transmission Electron Microscope (TEM) and X-ray diffraction (XRD) were used to
study the microstructure and components of the modified NZVI, and the 2,4
dichlorophenol 2,4-(DCP) removal efficiency was researched through chemical
experiment. Experiments showed that the modified NZVI was about 80~100 nm in
diameter, present as chain or dispersed particles. The main component was zero
valent iron, and it had strong reducibility. When the proportion of CMS was
80.00%, the suspension property was the best; The NZVI after CMS coating and
surface modification retained the original activity. In the experiment
investigating the removal effect of 2,4-DCP using different proportion of
cladding, the same finding was obtained. When the CMS's proportion was 80%, the
removal effect was the best, reaching up to 83.69%, and the dechlorination and
degradation were apparent.
PMID- 29965358
TI - [Enhancement of Sulfamerazine Degradation Under H2O2/KI System by Ultrasound and
UVA Irradiation].
AB - The degradation of Sulfamerazine(SMR) enhanced by molecular iodine under
ultrasound/H2O2/KI and UVA/H2O2/KI was investigated. The main affecting
parameters, iodine generation, active species and degradation products in the two
systems were discussed as well. The experimental results showed that
sulfamerazine degradation was effectively enhanced in both systems, and the
enhancement of ultrasound was much better. The initial pH had an obvious effect
on sulfamerazine removal in the range of 2.6-5.6, and the SMR removal efficiency
decreased with initial pH value. Iodine radicals (I2-., I.) were determined as
the main species in ultrasound/H2O2/KI and UVA/H2O2/KI systems. HPLC/MS/MS
analysis indicated that iodo-benzene was detected in both system.
PMID- 29965359
TI - [Comparison of Phosphate Adsorption onto Zirconium-Modified Bentonites with
Different Zirconium Loading Levels].
AB - In this study, zirconium-modified bentonites (ZrMBs) with different zirconium
loading levels were prepared, and the adsorption behaviors of phosphate on these
ZrMBs were comparatively investigated using batch experiments. The results showed
that the kinetic process of phosphate on ZrMBs well followed the pseudo-second
second kinetic model. The kinetic process was divided into three stages,
including a rapid external surface adsorption stage, a gradual adsorption stage
where both the intra-particle diffusion and film diffusion were rate-controlled,
and a final equilibrium adsorption stage. The equilibrium adsorption data of
phosphate on ZrMBs could be well described by the Langmuir, Freundlich, Sips and
Dubinin-Radushkevich isotherm models. Phosphate adsorption onto ZrMBs was more
favorable under strongly acidic condition than under weakly acidic or neutral
condition, while phosphate adsorption onto ZrMBs under weakly acidic or neutral
condition was more favorable than that under alkaline condition. Coexistence of
Na+ and K+ slightly enhanced phosphate adsorption onto ZrMBs, while coexisting
Ca2+ greatly enhanced the phosphate adsorption. The presence of HCO3- or SO2-4
inhibited the adsorption of phosphate on ZrMBs. The mechanism for phosphate
adsorption onto ZrMBs followed the ligand exchange and inner-sphere complexing
mechanism. The phosphate adsorption capacity for ZrMB increased with increasing
loading level of zirconium, while the amount of phosphate adsorbed on unit mass
of ZrO2 in ZrMB decreased with increasing loading amount of zirconium in ZrMB.
When the loading amount of ZrO2 in ZrMB increased from 3.61% to 13.15%, the
maximum phosphate adsorption capacity (MPAC) for ZrMB increased from 3.83 to 9.03
mg.g-1, while a further increase in the ZrO2 loading amount to 19.63% resulted in
a slight increase of MPAC to 9.66 mg.g-1. However, an increase in the loading
amount of ZrO2 in ZrMB from 3.61% to 19.63% caused a decrease of the MPAC for the
ZrO2 located in ZrMB from 106 to 49.2 mg.g-1. Considering both cost and
adsorption capacity of adsorbent, the ZrMB with 13.15% of zirconium loading
amount could be more suitably used as an adsorbent to remove phosphate from
aqueous solution than the other ZrMBs.
PMID- 29965360
TI - [Removal of Nitrogen in Municipal Secondary Effluent by a Vertical Flow
Constructed Wetland Associated with Iron-carbon Internal Electrolysis].
AB - Aiming at the problem of high concentration of total nitrogen (TN) and low
available carbon source for microorganisms in municipal secondary effluent, the
vertical flow constructed wetland associated with iron-carbon internal
electrolysis (ICIE-VFCW) was applied to investigate the removal efficiencies of
pollutants in municipal secondary effluent. Moreover, the mechanism for enhanced
nitrogen removal was primarily discussed by the applications of UV visible
spectrum (UV-VIS) and gel filtration chromatography (GFC). The results showed
that the ICIE-VFCW could improve the COD removal efficiencies and the effluent
COD of less than 30 mg.L-1could be stably obtained. The average COD removal
efficiencies of the whole year, warm months, and cold months could be increased
by 10.16%, 9.81%, 11.22%, respectively, compared to the control group. The
effluent TN of the ICIE-VFCW could be maintained below 10 mg.L-1, and the average
TN removal efficiencies of the whole year, warm months and cold months could be
increased by 13.72%,12.90%,16.17%, respectively. Besides, compared to the
influent, the humification, aromaticity and average relative molecular weight
(Mr) in the effluent obviously decreased, and the Mr decreased more significantly
in the ICIE-VFCW. The ICIE-VFCW could promote the conversion of refractory
organics in municipal secondary effluent to the small and readily biodegradable
molecules, which could enhance the utilization of organic compounds by
microorganisms, thus improving the removal efficiency of nitrogen.
PMID- 29965361
TI - [Purification Efficiency and Influencing Factors of Combined Bio-filters for
Aquaculture Wastewater].
AB - As an effective technology for wastewater treatment, bio-filter has been widely
used. Nevertheless, there is still a lack of systematic report on purification
efficiency and influencing factors of combined bio-filters. To this end, a novel
combined system that consisted of aerated vertical-flow filter (AVF) followed by
baffled horizontal-flow filter (BHF) was designed. After setting a series of
hydraulic loading rates (131, 94 and 60 mm.d-1) and diversion ratios
(8:2,6:4,4:6), we comprehensively assessed the impact of running condition
adjustment on treatment performance by multiple statistical analyses. The results
showed that, the average removal rates of organic matter, ammonia nitrogen and
dissolved nitrogen in AVF were all above 80%, while the average removal rates of
ammonia nitrogen, total nitrogen and dissolved nitrogen in BHF were all below
40%. Different running conditions had a significant (P<0.05) impact on treatment
performance. Meanwhile, there were significant differences in purification
efficiency between the two different kinds of filters. Oxidative degradation was
one of the main ways to remove organic matter in the two kinds of filters. There
were obvious nitrification and denitrification processes within the two kinds of
filters. Nitrification followed by denitrification was the main way to remove
total nitrogen since ammonium occupied the most portion of total nitrogen in the
synthetic wastewater. Meanwhile, the intensity of nitrification and
denitrification in AVF was obviously higher than that in BHF. Phosphorus removal
was mainly controlled by hydraulic loading rate, temperature, dissolved oxygen,
organic matter, etc. This might indicate that microbial absorption was one of the
main ways to remove phosphorus for the two filters. Compared to the sole AVF, the
removal of total organic matter and total phosphorus in the combined system was
increased by 4.4% and 23.2%, respectively, but the removal of total nitrogen was
reduced by 12.1%. Reducing the diversion ratio was helpful to improve the
denitrification intensity in BHF. However, due to the introduction of excessive
ammonia from the raw wastewater, as well as the limited nitrification capacity in
BHF, the removal rate of total nitrogen for the combined system was decreased.
Therefore, according to the composition of treated raw wastewater, the control of
appropriate diversion ratio, residence time and redox conditions inside the
filter bed was the key to enhance the overall performance of the combined system.
PMID- 29965362
TI - [Effect of Temperature on PAO Activity and Substrate Competition].
AB - To investigate the effect of temperature on the activity of high-temperature
phosphate accumulating organisms (PAOHT) and their competitive ability for the
substrate, the sludge from an enhanced biological phosphorus removal (EBPR)
reactor stably operated at the high temperature of 30C was used. The results
showed that PAOHT activity and their competitive ability for the substrate
increased with temperature increasing from 15C to 30C. When the temperature was
as higher as 30C, the rates of anaerobic phosphorus release, aerobic phosphorus
uptake and acetate uptake of PAOHT were 239.46 mg.(g.h)-1, 79.90 mg.(g.h)-1,
357.47 mg.(g.h)-1, respectively. The corresponding value of DeltaP/DeltaHAc was
0.628, which was considerably higher than that of PAO reported in literatures. A
simplified Arrhenius equation was used to describe the effect of temperature on
the rates of anaerobic phosphorus release, aerobic phosphorus uptake and acetate
uptake, and the temperature coefficients were 1.08, 1.07 and 1.05, respectively.
PMID- 29965363
TI - [Enrichment and Nitrogen Removal Characteristics of Marine Anaerobic Ammonium
Oxidizing Bacteria].
AB - In this work, enrichment and nitrogen removal characteristics of marine anaerobic
ammonium oxidizing bacteria were investigated by seeding sediment sludge from the
Jiaozhou bay. Experimental results showed that the whole process could be divided
into four phases:bacterial lysis phase (1-15 d), lag phase (16-152 d),
exponential growth phase (153-183 d) and stationary phase (184-192 d). Compared
to freshwater anaerobic ammonium oxidizing bacteria, the lag phase (137 d) was
longer. However, the exponential growth phase (30 d) was shorter. Besides, marine
anaerobic ammonium oxidizing bacteria were more sensitive to variation in
substrate concentration and HRT. The activity delay time caused by inflow and
effluent was 5 h, which was far longer than fresh anaerobic ammonium oxidizing
bacteria. As a result, the adaptive ability of marine anaerobic ammonium
oxidizing bacteria was weaker and it was harder to enrich. After successful
enrichment of 192 d, the removal rates of ammonia nitrogen and nitrite nitrogen
were 96.98% and 95.66%, respectively. n(NH4+-N):n(NO2--N):n(NO3--N) was 1:(1.2+/
0.2):(0.22+/-0.06), which was close to the theoretical ratio. NRRNH4+-Nwas 0.080
kg.(m3.d)-1, which indicated that the activity of marine anaerobic ammonium
oxidizing bacteria increased significantly. The enrichment of marine anaerobic
ammonium oxidizing bacteria was achieved. The sludge characteristics changed from
black to red. SEM observation confirmed that the red granule was cenobium, which
consisted of closely spaced micrococcus with smooth surface and crateriform
shape.
PMID- 29965365
TI - [Influence of Phosphate on Nitrogen Removal Efficiency of ANAMMOX Sludge].
AB - In this study, the effect of phosphate concentration on the nitrogen removal
efficiency of ANAMMOX sludge was researched. The inhibition kinetic parameters
were fitted and the abundance of ANAMMOX bacteria in the reactor before and after
phosphate inhibition was analyzed by Real-time PCR. The short-term experiments
showed that there was no significant effect on the nitrogen removal efficiency of
ANAMMOX sludge when phosphate concentration was less than 30mg.L-1. With the
increase of influent phosphate concentration, the removal rate of nitrogen
decreased rapidly. When the phosphate concentration was raised to 200mg.L-1, the
activity of ANAMMOX sludge reached a complete inhibition state. The parameters of
phosphate inhibition were fitted by Haldane inhibition model. The half-inhibition
constant was 70.1 mg.L-1. The long-term results showed that when the phosphate
concentration was less than 50 mg.L-1, the effect on the nitrogen removal
efficiency of ANAMMOX sludge was not significant. When the phosphate
concentration reached 70-90 mg.L-1, The activity of ANAMMOX sludge was obviously
affected, and the stability could be restored after a certain period. Increasing
the phosphate concentration had a more significant effect and resulted in a
longer recovery time. Finally, when the concentration of phosphate reached 100
mg.L-1, the nitrogen removal efficiency of ANAMMOX was seriously inhibited. The
rate of nitrogen removal decreased from 158.33 g.(m3.d)-1 to 60.17 g.(m3.d)-1,
resulting in 62% inhibition. The results of real-time PCR showed that the
concentration of ANAMMOX was decreased from (9.97+/-0.86)*107 cells.mL-1 to
(8.26+/-0.54)*107 cells.mL-1 in the restraining sludge system, and there was a
relatively reduced trend.
PMID- 29965364
TI - [Ammonia Removal Rate and Microbial Community Structures in Different Biofilters
for Treating Aquaculture Wastewater].
AB - Three MBBRs and three curtain type trickling filters (CTFs) with different
carriers were operated in lab-scale simulated RASs. The characteristics of
biofilms, ammonia removal rates and microbial communities in six reactors were
compared with each other. Compared with the biofilms of MBBRs, the biofilms of
CTFs were heavier and grew faster. The weight of biofilms on CTFs with carbon
fiber carriers was the maximum (45.97 g.m-2), and the ammonia nitrogen removal
efficiency (86.76%) of this CTFs was higher than the other filters or reactors
(61.96%~78.76%). In addition, the concentration of the accumulated nitrite in the
carbon fiber CTFs was the lowest in all the six reactors. The microbial
communities of biofilms in the six biofilters were evaluated by the high
throughput Illumina-MiSeq sequencing technology. The results showed that the
microbial (bacteria and eukaryote) community in biofilms of CTFs was different
from that in biofilms of MBBRs. At both bacteria and micro-eukaryote level, the
species richness and biological diversity of biofilms in the trickling filters
were higher than those in the MBBRs. On the contrary, the Simpson index of
bacterial community in biofilms of MBBRs was higher than that in the trickling
filters. In all the six biofilters, Nitrospira and Nakamurella were the dominated
bacterial genera. Saprospiraceae was more abundant in CTFs than in MBBRs, but
Comamonadaceae was enriched in the MBBRs. At the micro-eukaryote genus level,
Rhabditida norank genus was more abundant in CTFs, while Chlorophyceae norank
genus was more abundant in the MBBRs. The results provide useful information
about microbial ecology that can be used for the application of CTFs in RAS.
PMID- 29965366
TI - [Characteristics and Mechanism of Biological Nitrogen and Phosphorus Removal
Granular Sludge Under Carbon Source Stress].
AB - In SBR reactor, the mature granular sludge fed with sodium acetate was gradually
cultivated with different carbon sources (sodium acetate/glucose ratio was 1:0,
3:1, 1:1, 1:3 and 0:1, in terms of COD, respectively). During the five stages,
the physical, biochemical properties, extracellular polymeric substances (EPS),
phosphorus fractions and nitrogen and phosphorus removal efficiency of granular
sludge were studied. 705 days' experimental results were showed as follows. At
stage IV, the granular sludge had the smallest diameter of 0.5 mm; moreover the
phosphorus release/uptake rate, denitrification rate and the total phosphorus
(TP) content were the lowest. While at stages I and II, the phosphorus
release/uptake and denitrification rates were the highest, meanwhile, the TP
content reached up to 72.36 mg.g-1, and the EPS content was about 350 mg.g-1, as
a result, the nitrogen and phosphorus removal efficiencies were both over 94%.
Nevertheless at stage V, the biochemical rates were slightly slower than values
of stages I and II, simultaneously the TP, glycogen and EPS contents in sludge
were maintained at 69.60 mg.g-1, 224.18 mg.g-1 and 200 mg.g-1, respectively,
while high nitrogen and phosphorus removal efficiency was obtained. During all
stages, Ca-P was the main phosphorus fraction, and inorganic phosphorus(IP) was
closely related to phosphorus removal of granular sludge.
PMID- 29965367
TI - [Evolution of Extracellular Polymeric Substances of the Activated Sludge with
Calcium Ion Addition During Set-up Period of Sequencing Batch Reactors].
AB - Great attention has been paid to accelerate the start-up period and enhance floc
properties and structural stability in activated sludge reactors with the aid of
inorganic chemical agents such as calcium ion. The laboratory-scale sequencing
batch reactors (SBRs) were operated continuously for 35 days to investigate the
effect of calcium ion (Ca2+) on the physicochemical properties and evolution of
extracellular polymeric substances (EPS) of activated sludge during set-up
period. When compared to the control (non-calcium ion addition), the addition of
150 mg.L-1Ca2+ to the influent significantly increased the mixed liquid suspended
solids (MLSS) and the mixed liquid volatile suspended solids (MLVSS) by 89.6% and
75.6% on 28 d, respectively, and decreased the sludge volume index (SVI) by 47.9%
following SBRs set-up. Compared with the control system, the contents of EPS,
polysaccharides (PS) and proteins (PN) were increased by 76.4%, 28.8% and 31.6%
under the condition of Ca2+ dosage of 150 mg.L-1. The PS/PN ratio was 68.8 for
Ca2+ addition, compared to only 36.6 for the control reactor. Analysis using
three-dimensional excitation emission matrix fluorescence spectroscopy and
Fourier transform infrared spectrum revealed that Ca2+ addition changed the
compositional characteristics of EPS. Results from this study provided a
fundamental knowledge basis for the improvement of the settling properties of
activated sludge with calcium ion addition.
PMID- 29965368
TI - [Isolation, Identification and Characterization of the Filamentous Microorganisms
from Bulking Sludge].
AB - To illustrate the species and characteristics of filamentous microorganisms in
bulking sludge, culture method, microscopic examination and molecular biological
analysis were conducted to isolate and identify the filamentous microorganisms
existing in bulking sludge collected from municipal wastewater treatment plant.
Filamentous microorganisms isolated by Gause's synthetic agar medium and starch
agar fell into 18 genera, among which Streptomyces and Microbacterium belong to
bacterial phylum Actinobacteria, all other isolates were classified into fungi.
Penicillium, Cladosporium, Alternaria, Aspergillus and Trichosporon were the
fungi with high occurrence frequency in culture medium. Trichosporon,
Streptomyces, Penicillium and Alternaria could grow well at neutral pH or meta
acid condition. High concentration of NaCl could inhibit the growth of
Trichosporon and Streptomyces, but had no obvious inhibitory effect on
Penicillium and Alternaria. Except of Trichosporon, Streptomyces, Penicillium and
Alternaria all could utilize saccharose, starch and cellulose. The increase of
carbon source concentration could promote their growth. The results of high
throughput sequencing of rDNA-ITS showed that a large number of unidentified
fungi existed in bulking sludge.
PMID- 29965369
TI - [Applicability and Microbial Community Structure of Denitrification Suspended
Carriers].
AB - In order to investigate the effects of temperature and organic loading on the
bioactivity reactivation of anoxic biofilm in suspended carriers, the experiment
was carried out under low organic loading, shock loading and low temperature
conditions. The experimental results showed that the increase of polysaccharide
in extracellular polymeric substance (EPS) was important during bioactivity
reactivation process, and polysaccharide content was higher than that of protein
under shock loading and low temperature conditions, and the contents of both
polysaccharide and protein were much higher under low organic loading condition.
Anoxic biofilm achieved excellent applicability in shock loading condition,
moreover anoxic biofilm reactivated under low organic loading had lowest
denitrication capacity and anoxic biofilm recovered at low temperature was in
between. In addition, the relative abundance of Proteobacteria under low organic
loading, shock loading and low temperature conditions increased from 72.23%,
78.66% and 76.35% to 83.17%, 84.30% and 80.46% at the end of the reactivation
process (25th day), respectively. However, the relative abundance of
Proteobacteria under low organic loading was lower than those of other reactors,
indicating that the anoxic suspended carriers were less suitable for total
nitrogen removal in wastewater treatment plant. The increase in relative
abundance of Dechloromonas was significant for enhancing total nitrogen removal,
and anoxic biofilm possessed comparatively rich biodiversity when the
denitrification capability was recovered. The presence of Flavobacterium could
promote the denitrification capacity of biofilm at low temperature.
PMID- 29965370
TI - [Effect of Thiosulfate on the Carbon Fixation Capability of Thiobacillus
thioparus and Its Mechanism].
AB - The effect of Na2S2O3.5H2O on the carbon fixation capability of Thiobacillus
thioparus(DSM 505) was determined by measuring the total organic carbon (TOC)
concentrations under different concentrations of Na2S2O3.5H2O. In addition, the
mechanism was clarified by analyzing the transcription characteristics of RubisCO
encoding genes (cbb genes) and the concentrations of extracellular free organic
carbon (EFOC) under different concentrations of Na2S2O3.5H2O. The result showed
that by increasing the concentrations of Na2S2O3.5H2O appropriately, the carbon
fixation capability of Thiobacillus thioparus could be promoted and the ratio of
extracellular free organic carbon to total organic carbon fell significantly.
Moreover, the analysis from the transcription characteristics of cbb genes
revealed that Na2S2O3.5H2O had no significant effect on the transcription
efficiency and transcription pattern of cbb genes. So Na2S2O3.5H2O might improve
the carbon fixation capability by promoting the cytoskeleton synthesis rate as
electron donors to eliminate the inhibition effect of extracellular free organic
carbon on the carbon fixation of Thiobacillus thioparus.
PMID- 29965371
TI - [Characteristics of Fungi Community Structure and Genetic Diversity of Forests in
Guandi Mountains].
AB - Soil microorganisms drive the biogeochemical process of carbon, nitrogen,
phosphorus and sulfur, and play a key role in maintaining soil carbon sink and
ecosystem function. The study on effects of environmental and spatial factors on
the structure of microbial community in boreal coniferous forest soil will
provide theoretical basis for making management measures in local forest
ecosystem. Our research analyzed five soil fungi communities (LpMC1, LpMC2, PwMC,
PtMC, and BMC) in four forest types, including Larix principis-rupprechtii
forest, Picea wilsonii forest, Pinus tabulaeformis forest and Betula spp. forest,
respectively, in Pangquangou Nature Reserve in Guandi Mountains with Illumina
high-throughput sequencing technology. Meanwhile, soil environmental factors and
diversity of undergrowth plants were determined to analyze the relationship
between fungi community structure and vegetation as well as soil environmental
factors. The results showed that:1There were seven eumycota and thirty-three
advantageous fungal genera in the five sample sites; 2Redundancy analysis results
showed that soil pH, temperature, moisture, total nitrogen, the content of NH4+,
total carbon, invertase activity, urease activity, undergrowth dominance and
evenness were significantly associated with soil fungi community structure;
3Cluster analysis and principal component analysis showed that forest vegetation
type, soil environmental factors and undergrowth had significant effects on soil
fungi community structure; 4The results of PCNM analysis showed that at a local
scale, dispersal limitation had no significant influence on fungi community
structure in the study area. The forest soil fungi community structure in the
study area was significantly affected by environmental selection (soil pH,
temperature, moisture, total nitrogen, the content of NH4+, total carbon,
invertase activity, urease activity, undergrowth dominance and evenness, forest
type).
PMID- 29965372
TI - [Source Apportionment of Soil Heavy Metals in City Residential Areas Based on the
Receptor Model and Geostatistics].
AB - The soils from residential areas of Xi'an city were selected as a case area. The
absolute principal component scores-multivariate linear regression (APCS-MLR)
model and the ordinary kriging interpolation were combined to identify and
apportion the pollution sources of soil heavy metals (As, Ba, Co, Cu, Mn, Ni, Pb,
Sr, Zn,V), the percentage of contribution of every source for every element, and
the spatial distribution characteristics of contribution rates. Compared with the
background values of cinnamon, which is the main soil type in Xi 'an, the
accumulation levels of Pb, Cu, Sr, Co, Zn, Ba, Ni, As, Mn, V in soil of urban
residential areas in Xi'an city decreased in turn. The standard-exceeding ratios
of Ba, Co, Cu, Pb, Sr, Zn were higher than those of other studied elements. Three
main pollution sources of soil heavy metals in residential areas were natural
source, traffic sources, and fossil fuel combustion source, respectively. Natural
source was the main source of As, Mn, Ni, V in studied residential areas. The
average contribution rate of natural source for As, Mn, Ni, V was 69.63%, 74.28%,
68.65%, 77.09%, respectively. The fossil fuel combustion was the second largest
contributor for their accumulation in these studied residential areas. Its
contribution rate for As, Mn, Ni was 23.07%, 19.09%, 23.13%, respectively. The
contribution of traffic emissions was lower. Their spatial distribution
characteristics tended to be lower in west and higher in east. The average
contribution rates of fossil fuel combustion source for Co, Pb, Sr, Zn were
59.84%, 42.22%, 44.50%, 44.44%, respectively. The performance of spatial
distribution was increased gradually from the city center to the outside. The
sources of Ba were given priority to natural source and fossil fuel combustion
source, and the average contribution rates were 41.67% and 48.27%, respectively.
The contribution rate of fossil fuel combustion source for Ba gradually decreased
from the center of the city. The contribution rates of natural source, traffic
source, and fossil fuel combustion source for Cu were 37.00%, 20.47% and 26.50%,
respectively.
PMID- 29965373
TI - [Environmental Health Risk Assessment of Contaminated Soil Based on Monte Carlo
Method: A Case of PAHs].
AB - In order to obtain more reasonable health risk values and get the most
significant factors, probabilistic risk models based on Monte Carlo simulation
were applied, the health risk level of 16 PAHs in soil was evaluated for a
residential area in Shanghai, China. And, sensitivity analysis was conducted for
each parameter. The results showed that, the health risks caused by PAHs followed
lognormal distribution with 3.43*10-5+/-2.63*10-5 for carcinogenic risk, which
was between 8.10*10-7 and 2.39*10-4 and the probabilities exceeding 10-6, 10-5
and 10-4 were 95%, 75% and less than 5%. And the value was 4.74*10-2+/-3.42*10-2
for hazard quotient, which was between 1.38*10-3 and 2.85*10-1 and less than 1,
so could be regarded negligible. As for total carcinogenic risk (TCR), the most
influential PAHs were BaP, DBA and BaA, and their contribution rates were 60.41%,
26.84% and 6.56%, respectively. Among the three exposure pathways, the risk was
mainly caused by oral intake with the contribution rate of 73.22%, followed by
dermal contact with 26.51%. The most influential parameters were:intake amount of
soil per day, exposure duration and exposed skin area with the sensitivity values
of 58.35%, 50.21% and 20.51%, respectively. And body weight had a negative
sensitivity with -11.66%. When it came to total hazard quotient (THQ), Pyr, FL
and PA accounted for the most with 36.56%, 33.18% and 13.18%, respectively. And
the oral intake and dermal contact were also primary exposure pathways with
72.21% and 26.36%. The most significant parameters were the same with TCR with
the sensitivity values of 63.52%, 53.18%, 24.39% and -13.98%, respectively.
PMID- 29965374
TI - [Influencing Mechanism of Eh, pH and Iron on the Release of Arsenic in Paddy
Soil].
AB - The massive release of soil arsenic and its enrichment in rice are significantly
associated with the flooded and anaerobic management in paddy soil. Soil redox
potential (Eh), pH and iron oxides exert remarkable impacts on arsenic release,
which remain to be explored. In this study, long-term aerobic and anaerobic as
well as intermittent aerobic incubation treatments were applied to investigate
the influences of Eh, pH and iron content on arsenic release. It was found that
anaerobic and flooded treatment contributed to the highest arsenic release. With
decreasing Eh, significant enhancement in As(III) and As(V) contents in soil
solution was observed. Particularly, As(III) and As(V) contents during the second
phase increased by 1.37 and 0.99 MUg.L-1compared with those in the first phase.
Conversely, significant reduction in soil arsenic release (P<0.05) occurred when
intermittent aerobic treatment was adopted, and the lowest level of arsenic
release was observed along with the longest treatment time (6 d). The exponent
relationships between arsenic and soil Eh, pH and Fe2+ content were also
established, which indicated that arsenic release could be accelerated by lower
pH and elevated Eh. In addition, a significant positive correlation was also
found between iron(II) content and arsenic content in soil solution. Since low Eh
and elevated pH served as critical factors driving arsenic release, intermittent
and aerobic water management was proved to be an effective method for the
inhibition of arsenic release and uptake and accumulation of arsenic by rice.
PMID- 29965375
TI - [Correlations Between Different Extractable Cadmium Levels in Typical Soils and
Cadmium Accumulation in Rice].
AB - Pot experiments were used to study the correlations between different extractable
cadmium levels in typical soil and cadmium accumulation in rice. To analyze the
pH, Cd in soil solution(SSE-Cd), TCLP extractable Cd level(TCLP-Cd), and Cd
accumulation in rice at different growth stages of rice, we conducted pot
experiments which selected the reddish clayey soil(developed from quaternary red
clay parent materials) and purple paddy field(developed from purple sandy shale
parent materials), meanwhile added with exogenous Cd with the gradients of 0,
0.5, 1, 2, 5, 10 mg.kg-1. The results showed that, during the rice growth period,
the content of SSE-Cd in reddish clayey soil was in the range of 0 and 2.5 MUg.L
1, and the average content was 0.57 MUg.L-1; TCLP-Cd was in the range of 0 and
0.25 MUg.L-1 with the average content of 0.10 mg.kg-1;The content of SSE-Cd in
purple paddy field was in the range of 0 and 1.6 MUg.L-1 with the average content
of 0.48 MUg.L-1; TCLP-Cd was in the range of 0 and 0.2 mg.kg-1, and the average
content was 0.07 mg.kg-1. It showed that the cadmium concentrations in soil
solution and the TCLP extractable Cd levels were both significantly reduced in
two types of soil with the extension of rice growth period, and the content in
reddish clayey soil was higher than that in purple paddy. The TCLP extractable Cd
level was significantly positively correlated with Cd concentration in soil
solution. The total Cd accumulation in rice plants gradually increased with
increasing exogenous Cd concentration. There were significant positive
correlations between Cd concentration in soil solution and Cd concentration in
rice, Cd concentration in soil extracted by TCLP method and Cd concentration in
rice and total Cd accumulation in rice plant. The soil environmental capacities
of the two different parent materials varied greatly,and the safety threshold of
Cd in purple paddy field was 2.06 times of that of reddish clayey soil. There
were significant differences in Cd uptake and accumulation in different soils, so
different measures may be needed to control Cd pollution in different parent
materials. TCLP extractable Cd was more relevant with total Cd accumulation in
rice, and had more extraction amount. Therefore, the TCLP method can more
accurately evaluate the biological availability of soil Cd.
PMID- 29965376
TI - [Remedying Effects of a Combined Amendment for Paddy Soil Polluted with Cd for
Spring and Autumn Rice].
AB - An in-situ paddy experiment was conducted to study the remedying effects of a
combined amendment(calcium carbonate+diatomite+ferric sulfate) on Cd
bioavailability in soil and Cd accumulation in rice for spring and autumn rice
planted in a certain Cd contaminated paddy soil in Beishan Town, Changsha, Hunan
Province. The results showed that:Application of the combined amendment
significantly increased soil pH and CEC values in both cultivated seasons, but
decreased soil OM contents for the spring rice. During the experiment, the
contents of TCLP-extractable Cd and CaCl2-extractable Cd in soil were reduced by
18.0%-33.0% and 5.4%-57.9%, respectively. The Cd contents in brown rice, husk,
leave and root for the spring rice decreased by 29.6%-56.1%, 52.1%-54.0%, 18.1%
80.7% and 24.4%-41.6%, respectively, due to application of the combined
amendment. There were significant differences in Cd transport capacity between
spring rice and autumn rice, and the transportation of soil Cd in autumn rice was
smoother than that in spring rice. For the autumn rice, the effects of the
combined amendment were not significant(P>0.05), except that the Cd content in
husk increased a little after applying 2 g.kg-1 of the combined amendment.
Significant positive correlations were found between the Cd contents in brown
rice and the contents of TCLP-extractable Cd or CaCl2-extractable Cd in soil.
Application of the combined amendment effectively inhibited Cd uptake by rice
root and reduced Cd content in brown rice for the spring rice; however, these
remedying effects were significantly weakened for the autumn rice due to loss of
the combined amendment with the movement of irrigation water in the spring
season. Therefore, we suggest that supplement of the combined amendment is
necessary between two rice cultivated seasons.
PMID- 29965377
TI - [Effects of Two Amendments on Remedying Garden Soil Complexly Contaminated with
Pb, Cd and As].
AB - This paper studied the effects of two amendments (iron sulfate[Fe2 (SO4)3] and
calcium carbonate[CaCO3]) on the bioavailability of Pb, Cd and As in a garden
soil and on the migration and accumulation of Pb, Cd and As in pepper through an
in-situ experiment planting pepper plants. The results indicated that:1Addition
of these amendments significantly decreased TCLP extractable contents of Pb and
Cd in soil, and increased TCLP extractable contents of As.2Compared with the
control group, addition of Fe2 (SO4)3 led to reduction in contents of Pb and Cd
in pepper fruits by 7.2%-22.9% and 2.3%-2.9%, respectively, but no obvious
changes were observed for As contents in pepper fruits. Meanwhile, addition of
CaCO3 decreased the contents of Pb, Cd and As in pepper fruits by 15.8%-16.3%,
11.8%-15.0%, and 0.03%-53.2%, respectively. 3The maximum reductions for the
translocation factors of Pb, Cd and As from stem to fruits in pepper plants were
16.7%, 68.0%, 10.2%, respectively, due to Fe2(SO4)3 application and 16.7%, 51.5%,
45.6%, respectively, due to CaCO3 application, compared with the control group.
It was obvious that Fe2 (SO4)3 and CaCO3 could both effectively decrease the
migration of soil Pb, Cd and As to pepper plants, but the effects of CaCO3 were
better than those of Fe2 (SO4)3.
PMID- 29965378
TI - [Sorption of Phenanthrene to Soybean and Wheat Roots and the Bioavailability of
Sorbed Phenanthrene].
AB - The study of PAHs sorption and bioavailability to different crop roots could help
to reveal the environmental behavior of PAHs in the ecosystem and evaluate the
ecological risk of PAHs. However, there is little information about the
differences in PAHs sorption to different roots and the bioavailability of the
sorbed PAHs. In this paper, the experiments were conducted on the
sorption/desorption of phenanthrene to soybean and wheat roots under different
sorption times and different phenanthrene concentrations. The results showed that
the trend of phenanthrene sorption in vivo was first increased and then decreased
and finally reached a balance, which was related to the transport delay in vivo;
the trend in dead and dried roots was first increased and then reached a balance.
The greater specific surface area and the higher fat content, the faster the
balance was. Freundlich isotherm was fitted better than Henry isotherm for dead
and dried roots, Langmuir isotherm was best fitted in wheat roots. All of the
fitted isotherms indicated that the distribution and the surface adsorption could
control the phenanthrene sorption. Because of the special binding between living
roots and phenanthrene, the fit effect was poor. The phenanthrene sorption
capacity of soybean roots was higher than that of wheat, which was related to the
high water content, fat content and membrane permeability. The phenanthrene
sorbed on the roots was hard to desorb, and the desorption trends were wheat
roots> soybean roots; living roots> dried roots> dead roots. The bioavailability
of root-sorbed phenanthrene was consistent with the desorption results. Our
results could provide data for the assessment of environmental risks of PAHs
sorbed onto crop roots.
PMID- 29965379
TI - [Effects of Dissolved Organic Matter Fractions Extracted from Humus Soil on
Sorption of Benzotriazole in Brown Soil and Black Soil].
AB - Dissolved organic matter (DOM) affects the sorption behavior of organic
pollutants in soils. In this study, bulk DOM (marked as DOMbulk) was extracted
from natural humus soil and divided into five individual fractions by XAD-8 resin
and anion/cation exchange resins based on their hydrophobicity-hydrophilicity.
The isolated DOM fractions were characterized by FTIR, elemental analysis, UV
spectrophotometer and potentiometric titration. Batch experiments were conducted
to investigate the effects of different fractions of DOM on sorption of
benzotriazole (BTA) in two Chinese reference soils (brown soil and black soil).
Proportions of hydrophobic acid (HOA), hydrophobic neutral (HON), hydrophilic
acid (HIA), hydrophilic base (HIB) and hydrophilic neutral (HIN) in DOMbulk were
61%, 17%, 6%, 2% and 14%, respectively. Sorption affinity of BTA and DOM in black
soil was greater than that in brown soil, which was attributed to the higher
organic carbon (OC) content of black soil as compared to that of brown soil.
Brown soil had higher normalized distribution coefficient Koc of sorbed DOM
fractions than black soil, because brown soil has a greater proportion of clay
and silt, which play important roles in sorption of DOM fractions. Dialysis-bag
experiments demonstrated that binding coefficient between each isolated DOM
fraction and BTA in solution was very weak. The reason is that the binding sites
of DOM are occupied by water molecules in solution. Among the isolated DOM
fractions, HIN showed the strongest sorption affinity in both soils, which
increased OC content and consequently produced new sorption sites in soils. The
enhanced sorption effect from new sorption sites was greater than that from
competitive sorption between BTA and HIN. On a whole, HIN enhanced the sorption
of BTA in soil. HOA and HON inhibited the sorption of BTA in soils. Because the
sorption of hydrophobic fractions, especially HON, in soils was less than that of
other fractions, competitive sorption between hydrophobic fractions and BTA was
the main mechanism. DOMbulk that consists of 78% hydrophobic fractions had
similar effects with hydrophobic fractions on sorption of BTA in two soils.
PMID- 29965380
TI - [Effects of Topography, Tree Species and Soil Properties on Soil Enzyme Activity
in Karst Regions].
AB - Soil extracellular enzymes are crucial in biogeochemical cycle and ecosystem
functioning. Yet uncertainty exists in terms of major determinants on soil
extracellular enzyme activity (EEA), especially at calcareous areas. In this
study, soil samples (0-15 cm) were collected from different topographic
conditions (different slope positions and aspects) and different tree species
(Cryptocarya concinna and Eurycorymbus cavaleriei) in a forest located at Mulun
natural reserve, a typical karst area. Six hydrolytic enzymes, related to carbon,
nitrogen or phosphorus cycling, and soil physiochemical properties were
investigated. The effects of topography, tree species and soil properties on soil
enzyme activities were analyzed by multi-response permutation procedures (MRPP),
redundancy analysis (RDA) and variation partitioning. The enzyme profiles were
significantly (P<0.05) separated among the four slope positions but not
significantly separated between the two aspects or two tree species according to
multi-response permutation procedure (MRPP) analysis. Variation partitioning
indicated that topography, tree species and soil properties together explained
55.3% of EEA variation. Soil property was the key factor influencing EEA
variation, which explained 44.2% of EEA variation. The result of redundancy
analysis (RDA) showed that soil pH, total nitrogen and inorganic nitrogen were
the most important variables among the nine soil properties for EEA variation.
This study first quantified the effects of small-scale topographic, tree species,
and soil properties on soil enzyme activity variation in karst areas. Our results
suggest that EEA variation can be well explained by soil properties at a small
scale in the karst area.
PMID- 29965381
TI - [Effects of Long-term Organic Amendments on Soil N2 O Emissions from Winter Wheat
maize Cropping Systems in the Guanzhong Plain].
AB - The primary aim of this study was to quantify the effects of long-term organic
amendments on soil nitrous oxide (N2O) emissions. Using static chamber-gas
chromatograph technique, we measured N2O fluxes from winter wheat-maize rotation
system and related environmental factors in the Guanzhong Plain for one year
(October 2014 to October 2015). Field experiments were based on the "Chinese
National Loess Fertility and Fertilizer Effects Long-term Monitoring Experiment".
Four treatments were control (CK, 0 kg.hm-2), NPK (NPK, 353 kg.hm-2), NPK
combined with maize straw[NPKS, (353+40) kg.hm-2] and cattle waste[NPKM,
(238+115) kg.hm-2]. During the experimental period, N2O fluxes from CK treatment
were small[<2.9 g.(hm2.d)-1]; while emissions from fertilized treatments peaked
after fertilization[up to 113.4 g.(hm2.d)-1 for NPKS] and irrigation[up to 495.0
g.(hm2.d)-1 for NPKM] during winter wheat and maize seasons, respectively. N2O
flux was significantly correlated to soil water-filled pore space for all
treatments (r>0.28,P<0.05). Annual N2O emissions were (0.1+/-0.0), (2.6+/-0.1),
(3.4+/-0.7) and (2.9+/-0.3) kg.hm-2 for CK, NPK, NPKS and NPKM, respectively. The
fertilized treatments released higher N2O emissions than CK treatment (P<0.05),
indicating that fertilization stimulated N2O emissions. However, the differences
in N2O emissions were not significant among the fertilized treatments (P=0.06),
suggesting that organic amendments did not increase N2O emissions obviously. The
direct emission factors were 0.72%, 0.83% and 0.80% for NPK, NPKS and NPKM,
respectively, all of which were lower than the IPCC default of 1%. The yield
scaled N2O emission for NPKM was the lowest among the fertilized treatments.
PMID- 29965382
TI - [Exposure Route of Dioxin-like Polychlorinated Biphenyls in Hair Based on Passive
Sampling].
AB - The main exposure pathways of DL-PCBs in local population were studied by
analyzing the levels, distributions and relationships of DL-PCBs in pooled tree
bark samples and hair samples collected in Kaiyuan, Yunnan Province, China. The
results indicated that the concentrations of DL-PCBs in bark and hair samples
were 4.0 pg.g-1 to 88.9 pg.g-1 and 4.1 pg.g-1 to 19.3 pg.g-1, respectively,
suggesting the pollution levels of DL-PCBs were relatively low in local
environment and human body. The predominant PCB congeners in bark and hair was
PCB-118, contributing 48% of the total DL-PCB concentrations in the bark samples
and 61% of the total DL-PCB concentrations in the hair samples. The DL-PCB
congeners in tree bark might had the same sources and these compounds might be
derived from atmospheric long-range transport. External and internal exposures
were responsible for the DL-PCBs concentrations in hair, and external exposure
contributed more to low chlorinated PCBs than to high chlorinated PCBs.
PMID- 29965383
TI - [Accumulation Characteristics and Health Risk Assessment of Heavy Metals in Wild
Fish Species from Diaojiang River, Guangxi].
AB - To explore the accumulation characteristics and health risk assessment of heavy
metals in wild fish species, the concentrations of heavy metals (Pb, Cd, Cr, As
and Hg) in the muscle samples of eight wild fish species collected from Diaojiang
River, Guangxi were analyzed. The degree of pollution, food safety and health
risk of heavy metals in wild fish species were evaluated using the average
pollution index and the target hazard quotient methods. The results showed that
the concentrations of Pb, Cd, Cr, As and Hg in wild fish species ranged from
0.041 to 1.160, 0.0001 to 0.066, 0.173 to 0.789, 0.010 to 2.420 and 0.0007 to
0.077mg.kg-1, respectively. The concentrations of Pb and As in wild fish species
exceeded the limit values of the Maximum Levels of Contaminants in Foods (GB 2762
2012), and the over-standard rates were 5.06% and 64.56% respectively. The
concentrations of Cd, Cr and Hg did not exceed the standard. The average
pollution index results showed that Acheilognathus tonkinensis and Acheilognathus
barbatus were seriously polluted by heavy metals. The Oreochromis niloticus were
moderately polluted. The Siniperca kneri Garman, Carassius auratus,
Pseudohemiculter dispar, Ctenopharyngodon idellus, Hemiculter leucisculus were
slightly polluted. Higher bioaccumulation factors of Pb, Cr and Hg were found in
wild fish species from Diaojiang River. The concentrations of heavy metals in
carnivorous fish and omnivorous fish were higher than those in herbivorous fish.
Potential health risk assessment showed that the total target hazard quotients
(TTHQ) of Acheilognathus tonkinensis and Acheilognathus barbatus were higher than
1. It indicated that the local residents posed higher human health risk due to
the long-term consumption of Acheilognathus tonkinensis and Acheilognathus
barbatus. Among all the TTHQ in wild fish species (except Pseudohemiculter dispar
and Hemiculter leucisculus), the contribution rate of As was the highest, and the
average contribution rate reached 76.63%, which indicated that As was the main
risk factor.
PMID- 29965385
TI - [Volatile Organic Compounds(VOCs) Source Profiles of Industrial Processing and
Solvent Use Emissions: A Review].
AB - Industrial processing and solvent use are two most important industrial sources
of volatile organic compounds (VOCs) in China, and the source profile study has
attracted increasing attention recently. Studies of VOCs source profiles from
industrial processing and solvent use since the year of 2000 were summarized in
this study, focusing on the comparison among different studies and the potential
impact of different research methods. In general, studies were very limited and
focused on few sources. Specifically, only 8 of 32 sub-categories of the
industrial processing (according to the source classification method of the
National Guidelines for VOCs Inventories Preparation) have been reported, and in
terms of the solvent use sources, 4 of 10 sub-categories have been reported.
There were large differences among the VOCs patterns of different sub categories
emissions of industrial processing or solvent use. In terms of studies of the
similar emissions, significant differences of VOCs profiles were resulted from
the different research methods, such as the different sampling methods and VOCs
analysis techniques. In addition, the non-uniformity of VOC species in the source
profile caused difficulty for the comparison of different research results.
Oxygen-containing VOCs were important components of the above two types of
pollution sources and needed to be included in the measurement. An opening and
interactive database of VOCs from industrial processing and solvent use is
critically essential in the future, and mechanisms of sharing and inputting
relative research results should be formed to encourage researchers to join the
database establishment. Correspondingly, detailed quality assurance and quality
control procedures are also very important, which include the detailed
information such as research objectives, sampling and analysis methods, research
region and time, and test times, et al. Based on the community above, a better
uncertainty analysis could be carried out for the VOCs emissions profiles, which
is critically important to understand the VOCs emission characteristics of the
industrial processing and solvent use.
PMID- 29965384
TI - [Effect of Activated Carbon Addition on the Anaerobic Fermentation of Corn Straw
in Mesophilic and Thermophilic Conditions].
AB - In order to improve the methane production and concentration, effect of activated
carbon addition on the anaerobic fermentation of corn straw under the conditions
of mesophilic temperature (38C) and thermophilic temperature(50C) was
investigated in this study. The results showed that the addition of activated
carbon could significantly promote methane production. Compared with the control
group in mesophilic and thermophilic conditions, cumulative methane production
could be increased by 63% and 96% in test groups. By DGGE analysis, the bacterium
enriched by addition of activated carbon was mainly Clostridiales bacterium,
compared to Bacillus (without adding activated carbon) in the thermophilic
system, while the differences in fermentation with adding activated carbon and
without adding activated carbon was not significant in the mesophilic system.
With addition of activated carbon, the archaea enriched in the fermentation
liquid was mainly Methanosaeta concilii in the mesophilic system, whereas the
archaea enriched in the fermentation liquid was mainly Methanosarcina acetivorans
in the thermophilic system. The archaea enriched on activated carbon was mainly
Methanosaeta concilii at mesophilic temperature, while the archaea enriched on
activated carbon was mainly Methanosarcina thermophila at thermophilic
temperature.
PMID- 29965386
TI - [Development of a Non-Road Mobile Source Emissions Inventory for Tianjin].
AB - Based on the collected data of activity level in 2015, a non-road mobile source
emissions inventory for Tianjin was developed following the recommended method
from the Compilation Guide for a Vehicle Emissions Inventory (trial edition)
released by the Ministry of Environmental Protection. In 2015, the emissions of
CO, hydrocarbons (HC), nitrogen oxides (NOx), particulate matter (PM) and SO2
from non-road mobile sources in Tianjin were 6.15*103 t, 2.45*103 t, 2.90*104 t,
1.45*103 t, and 1.37*104 t, respectively. Marine sources were identified as the
largest non-road mobile source contributor accounting for 73.66% of total
emissions, followed by non-road mobile machinery (21.66%). Emissions from civil
aircraft and locomotives were relatively lower. Generally, emissions from non
road mobile sources increase from March (spring) to November and decrease from
the beginning and the end of the year (winter). Emissions are mainly distributed
in suburban districts where there is flourishing agriculture, downtown areas with
dense populations, urban construction areas, ports, railway lines, and airports.
Uncertainty in the inventory results is mainly due to the lack of key data, such
as local emission factors and actual activity levels.
PMID- 29965387
TI - [Spatial Simulation of Black Carbon Concentrations Based on a Land Use Regression
Model and Mobile Monitoring over Shanghai, China].
AB - Black carbon (BC) is an important component of atmospheric pollution and has
significant impacts on air quality and human health. Choosing Shanghai city for a
case study, this paper explores the statistical characteristics and spatial
patterns of BC concentrations using a mobile monitoring method, which differs
from traditional fixed-site observations. Land use regression (LUR) modeling was
conducted to examine the determinants for on-road BC concentrations, e.g.
population, economic development, traffic, etc. These results showed that the
average on-road BC concentrations were (9.86+/-8.68) MUg.m-3, with a significant
spatial variation. BC concentrations in suburban areas[(10.47+/-2.04) MUg.m-3]
were 32.03% (2.54 MUg.m-3) higher than those in the city center[(7.93+/-2.79)
MUg.m-3]. Besides, meteorological factors (e.g. wind speed and relative humidity)
and traffic variables (e.g. the length of roads, distance to provincial roads,
distance to highway) had significant effects on on-road BC concentrations (r:0.5
0.7, P<0.01). Moreover, the LUR model, including meteorological and traffic
variables performed well (adjusted R2:0.62-0.75, cross validation R2:0.54-0.69,
RMSE:0.15-0.20 MUg.m-3), which demonstrates that on-road BC concentrations in
Shanghai are mainly affected by these factors and traffic sources to some extent.
Among them, the most accurate LUR model was developed with a 100 m buffer,
followed by the LUR model with a 5 km buffer. This study is of great significance
for the identification of spatial distribution patterns for on-road BC
concentration and exploring their influencing factors in Shanghai, which can
provide a scientific basis and theoretical support for simulating and predicting
the response mechanisms of BC on human health and the natural environment.
PMID- 29965388
TI - [Characteristics and Sources of Elements of a PM10 Measurements from a Typical
Industrial City in Eastern Hubei Province].
AB - In order to investigate the characteristics and sources of elements in
atmospheric aerosols (PM10) measurements, samples were collected between April
2012 and February 2013 in Huangshi, a typical industrial city in the east of
Hubei province, China. These samples were analyzed for seventeen elements using
wavelength dispersive X-ray fluorescence spectrometry. In addition, the pollution
characteristics of fourteen elements were analyzed by an enrichment factor (EF)
method, and the sources of these elements were studied by a principal component
analysis (PCA) and positive matrix factorization (PMF) method. The result from
the EF indicated that the concentration of the seventeen elements in the PM10
measurements varied from 0.01-9.83 MUg.m-3. The elemental concentration of S was
the highest and Ni and V was the lowest during the monitoring period in Huangshi.
Daily levels of Pb and Cd exceeded the annual reference values set by the
National Ambient Air Quality Standard (GB3095-2012) by 36.4% and 89.1%,
respectively. An analysis of EF showed that Ti, V, Mn, and Ni elements were
mildly enriched, indicating they were affected by both natural and anthropogenic
sources. Ca, Cr, and Ba elements were moderately enriched and Cu, Zn, Pb, Sn, Sb,
and Fe were highly enriched or hyper accumulated, suggesting they are mainly
sourced from human activities. There were four sources significantly contributing
to the elements in the PM10measurement, which were determined using PCA and PMF
analysis. These were soil and fugitive dust, coal combustion, industry exhausts,
and motor vehicle emissions. The results of the two models supported each other
and had good consistency.
PMID- 29965389
TI - [Characteristics and Source Identification of Carbonaceous Aerosols in PM2.5
Measurements During Summer and Fall in Changzhou].
AB - To better understand the characterization and sources of carbonaceous components,
a total of 60 fine particle (PM2.5) samples were collected in Changzhou during
summer (July to August) and fall (October to November) of 2016. The average mass
concentrations of PM2.5, organic carbon (OC), and elemental carbon (EC) during
this study period were observed to be 73.0, 14.3 and 3.3 MUg.m-3 in summer and
84.2, 13.2, and 3.5 MUg.m-3 in fall, respectively. The average mass fraction of
carbonaceous aerosols (OC+EC) in the PM2.5 measurement was estimated to be 24.3%
in summer and 20.7% in fall. Eight carbonaceous fractions, resolved by following
the IMPROVE-A thermal/optical reflectance protocol, showed strong correlation
(r>0.92) between OC2, OC3, OC4 and EC1 and close correlations between EC2 and EC3
(r>0.65), indicating probable similar contributors. OC and EC were moderately
correlated, suggesting complex contributions to carbonaceous aerosol. The water
soluble organic carbon (WSOC) to OC ratio (WSOC/OC) in the fall (60.9%) was
slightly higher than that in the summer (57.4%), while secondary organic carbon
(SOC) to OC ratio (SOC/OC) was lower in the fall (49.0%) compared with the summer
(52.5%). The SOC/OC ratio was lower than the WSOC/OC for both seasons, suggesting
that part of WSOC component originates from primary emissions. The significant
correlation of WSOC and SOC confirms that most SOC is water soluble.
Relationships between each carbonaceous species and the principal component
analysis indicate that vehicle emissions and coal combustion are the two main
emission sources of carbonaceous aerosols from the observation period. Back
trajectory analysis was used to indicate that carbonaceous components at sampling
site are mainly affected by local emission sources and short distance transport,
whereas the contribution of long-distance transmission is small.
PMID- 29965390
TI - [Characteristics and Sources of Water Soluble Inorganic Ions in Fine Particulate
Matter During Winter in Xuzhou].
AB - A total of 32 daily PM2.5 samples were collected from December 2016 to February
2017 in the urban area of Xuzhou city. Water-soluble inorganic ions (WSIIs),
including F-, Cl-, NO3-, SO42-, Na+, Mg2+, NH4+, K+ and Ca2+, were determined by
ion chromatography. The average mass concentration of PM2.5 was (164.8+/-77.3)
MUg.m-3 and the average total mass concentration of the nine ions was (67.5+/
36.1) MUg.m-3, the contribution of the WSIIs to the PM2.5 was more than 40.9%.
The order of the concentrations of individual ions was NO3- > SO42- > NH4+ > Cl-
> Ca2+ > K+ > Na+ > Mg2+ > F-. NH4+, NO3-, and SO42- (SNA) were the major
components of the water-soluble ions in the PM2.5 measurement. The average mass
concentration of WSIIs in clean air, mild haze, and severe haze was (12.8+/-8.8),
(59.0+/-22.8) and (86.3+/-36.0) MUg.m-3, respectively. The contribution of SNA to
WSIIs was 86.4%, 82.8%, and 78.9%, respectively. The correlation between each
component of SNA with each other was significant. NH4+, NO3-, and SO42- were in
the form of (NH4)2SO4 and NH4NO3. Secondary formation, biomass burning, fossil
fuel combustion, and dust were the major sources of the water-soluble ions in
PM2.5.
PMID- 29965391
TI - [Physiochemical Properties and Sources of Atmospheric Particulate Matter During
Pollution Monitoring in Nanning, China].
AB - Distribution characteristics, chemical constituents, and sources of particulate
matter were measured using a scanning mobility particle sizer and single particle
aerosol mass spectrometer during pollution monitoring that occurred between
December 5th and December 11th, 2016, in Nanning. Results showed that particulate
matter (PM) sized between 20 nm-10 MUm were concentrated in the 23 to 395 nm
range, with a peak of 100 nm. Three new particle types were generated during the
course of this monitoring. These new 30 nm particles came into existence between
14:00 to 18:00, and grew to a size of between 40 nm and 110 nm between 20:00 to
06:00 the next day. The generation of the all three new particles was affected by
motor vehicle exhaust emissions. Many secondary particles were also produced
during this period of pollution. The source of the fine particulate matter was
mainly from the burning of biomass, dust, and the combustion of coal. In
addition, a long-distance transmission also contributed to the particles from
biomass burning.
PMID- 29965392
TI - [Concentration and Size Distribution Characteristics of Culturable Bioaerosols at
Various Air Quality Levels During Fall and Winter in Xi'an, China].
AB - The concentration and size distribution of culturable bacteria and fungi were
studied in Xi'an city at various air quality levels. The culturable bioaerosols
were collected by an Andersen bioaerosol aerosol sampler between Sept. 2014 and
Jan. 2015. Principal component analysis and multiple linear regressions were
applied to link the concentrations with meteorological conditions including
ambient temperature and relative humidity, as well as the levels of air
pollutants such as PM2.5, PM10, NO2, SO2, and O3. These measured results showed
that the concentration of culturable bacteria and fungi were in the ranges of 97
1909 CFU.m-3 and 92-1737 CFU.m-3, respectively. The concentrations of culturable
bioaerosols increased along with a deterioration in air quality. The size
distribution of the bacteria migrated to coarse particles. Fungal aerosols showed
a normal distribution at low pollution levels, while for a high levels, they
preferenced fine particles. Results from the principal component analysis (PCA)
indicate that the concentration of culturable bioaerosols is mainly influenced by
haze, solar radiation, and relative humidity. Multiple linear regression analysis
showed that bacterial aerosol concentrations are positively correlated with haze
(P<0.05) and relative humidity, while no significant negative correlations with
solar radiation exists. Fungal aerosol concentrations did not have significant
positive correlations with haze, solar radiation, or relative humidity. The
results of this study will provide basic data for evaluating the effects of
bioaerosols on human health and the environment.
PMID- 29965393
TI - [Distribution Characteristics of Chromophoric Dissolved Organic Matter and
Nutrients from the Yellow Sea and Bohai Sea in Autumn].
AB - Water samples were collected from the Yellow and Bohai seas during November 2013
and the chromophoric dissolved organic matter (CDOM) and nutrients concentrations
were investigated, including their composition, source and distribution
characteristics. CDOM was analyzed by excitation-emission matrix spectroscopy
(EEMS) in combination with a parallel factor analysis (PARAFAC). Three
terrestrial humic-like substances (C1, C2, and C3) and one protein-like (C4)
substances were identified. The three terrestrial humic-like components had a
similar horizontal distribution, decreasing from inshore to offshore. The protein
like component, showed higher values for both inshore and offshore areas in the
Yellow Sea at the surface layer and the middle layer of the Bohai Sea, while in
other layers it had a similar distribution pattern as the terrestrial humic-like
components. In the Bohai Sea, the dissolved inorganic nitrogen (DIN)
concentration showed a decreasing trend from inshore to offshore areas and the
concentration of dissolved inorganic phosphorus (DIP) gradually decreased from
the Caofeidian coastal and central areas to other adjacent areas. The dissolved
organic nitrogen (DON) showed an increasing from inshore to the central area of
the Bohai Sea. DIN and DON were higher in surface layer than in the bottom layer
and for DIP this was the opposite in the Bohai Sea. In the Yellow Sea, DON
concentrations showed a decreasing trend from inshore to offshore areas. DIN and
DIP had higher concentrations at inshore areas in the surface and middle layers,
while in the bottom layer they had higher concentrations in offshore areas. The
vertical distribution of the DIN and DIP showed higher values in the bottom layer
than surface layers and for DON this was the opposite. These results also showed
that the concentrations of DIN, DON, and DIP in the Bohai sea were overall higher
than the Yellow Sea. A discriminant analysis was performed through redundancy
analysis (RAD) of these water quality parameters, including the four fluorescent
components, an absorption coefficient (a355), chlorophyll a concentration,
conductivity, dissolved oxygen (DO), dissolved organic carbon (DOC), DIN, DON,
and DIP. The RDA indicated that the four fluorescent components are mainly
affected by terrestrial inputs. DOC was affected by both terrestrial and marine
sources but terrestrial inputs were the major contributor. It was also indicated
that the DIN concentration was affected by terrestrial inputs in the Bohai Sea
area and by both terrestrial and marine sources in the Yellow Sea. DON
concentrations were mainly affected by marine sources in the Bohai Sea and
terrestrial inputs in the Yellow Sea. DIP concentrations were affected by both
terrestrial and marine sources in the studied areas.
PMID- 29965394
TI - [Characteristics and Risks of Heavy Metals Content in Surface Sediment of Tidal
Flat Areas in Eastern China].
AB - To understand the heavy metals content such as As, Cd, Cr, Cu, Hg, Pb, and Zn, as
well as their distribution features in surface sediments of tidal flat areas of
Eastern China, mathematical statistics, correlation analysis, factor analysis and
other statistical methods are used. This study collected 1906 surface sediment
samples of As, Cd, Cr, Cu, Hg, Pb, Zn were collected as part of a systematic
research effort. These results show that the coastal tidal flats zone of Eastern
China contains surface sediment samples with heavy metal concentrations (As, Cd,
Cr, Cu, Hg, Pb, and Zn) with is not high but has increased due to anthropogenic
sources. The total content of heavy metals in Jiangsu province is low, however,
in Shanghai and Zhejiang provinces relatively high heavy metal contents are
present. In addition to natural causes, the heavy metal content in coastal
sediment in Shanghai and Zhejiang is significantly affected by human activities,
while Jiangsu coastal surface sediments has light impacts from human activities.
Heavy metal contamination in coastal areas Shanghai, Zhejiang, and Fujian
provinces is particularly serious including Hg, Cd, and Cu contamination. The
results of an evaluation using the Marine Pollution Sediment Index and Mean
Sediment Quality Guidelines show that in Eastern China, the overall sediment
pollutant ecological risk is low for Jiangsu and Fujian provinces, however, the
ecological risk for the tidal flats of Shanghai and Zhejiang provincial beaches
is relatively high due to heavy metal concentrations.
PMID- 29965395
TI - [Heavy Metals in Sediments from the Haizhou Bay Marine Ranching Based on
Geochemical Characteristics].
AB - Marine ranching is a new sustainable production method, which plays an important
role in the transformation of China's marine economy. In this paper, Haizhou Bay
marine ranching was divided into 3 areas according to the intensity and delivery
time of the submarine structures. Five geochemical indicators of temperature (T),
pH, oxidation-reduction potential (Eh), grain size (D[3,2]) and total organic
carbon (TOC) were determined on-site. A modified European Community Bureau of
Reference(BCR)sequential extraction procedure was applied to determine the
chemical speciation of different heavy metals (i.e. Cr, Cu, Ni, Zn, Pb, and Cd).
The results showed a horizontal distribution of the Eh was influenced by the
submarine structures. The TOC content ranged from 11.7 to 13.5 g.kg-1, which had
a significant negative correlation with pH. Pb and Cd mainly present in the
secondary phase of iron manganese oxide forms (F2), which were controlled by the
Eh, however, Cu, Zn, Ni, and Cr were mainly present in the primary phase. A
correlation and cluster analysis indicated that the Cr, Cu, Ni, and Zn present in
sediments were from natural sources, while the Cd and Pb content obviously came
from anthropogenic metal sources. The exchangeable and carbonate fractions (F1)
of Cr, Ni, Cu, Zn, Pb, and Cd were significantly correlated with TOC. The
residuals (F4) of Cr, Ni, Cu, Zn, Pb, Cd were significantly correlated with the
grain size of sediments as well as the iron-manganese oxide forms (F2) of Cr, Ni,
Cu, and Zn. A different speciation of Cd was controlled by multiple geochemical
characteristics of the sediment. The heavy metal levels of the primary and
secondary phases in the central and lateral areas were lower than the control and
medial areas because of differences in the submarine structures and
hydrodynamics. The enrichment and adsorption of Cr, Ni, Cu, and Zn in sediment
was stronger than the release of particles that were resuspended. While the
influence of fine particles and organic matter from the sediment in the central
and outer areas was limited, an enrichment factor analysis suggested that Cd in
sediment showed enrichment to some extent. This paper provides a scientific basis
for the construction of marine ranching and ecological restoration in Haizhou
Bay.
PMID- 29965396
TI - [Major Ionic Features and Their Possible Controls in the Water of the Niyang
River Basin].
AB - In order to study the hydrochemical characteristics and their possible controls
for the chemical composition of the water from the Niyang River Basin, 30 samples
were collected from wells, springs, and the river in 2014 and major ion
concentrations were measured. Descriptive statistics, the Gibbs figure, an ion
ratio, and Piper triangular diagrams were used to investigate the hydrochemical
characteristics, influencing factors, and hydrochemical evolution of the water in
the basin. The results showed that the major cations in this water were Ca2+ and
Mg2+, accounting for more than 84% of cations and the main anions were HCO3- and
SO42-, accounting for more than 97% of anions The hydrochemical typology of the
water is HCO3.SO4(SO4.HCO3)-Ca.Mg (Mg.Ca). The total dissolved solids (TDS) in
the water ranges from 79.11 to 290.48 mg.L-1 with an average of 165.21 mg.L-1.
The chemical composition of water samples is located to the left of the Gibbs
model, which indicates that the chemical process of Niyang River Basin are
controlled by rock weathering. According to the principal component analysis and
correlation analysis, the hydrochemical composition is controlled by silicate
weathering, however, carbonate weathering also plays an important role.
PMID- 29965397
TI - [Vertical Distribution Characteristics of Fe and Mn in Subtropical Reservoirs
During Summer].
AB - Iron (Fe) and manganese (Mn) are redox-sensitive elements that are both important
chemical indicators of water quality. To study their vertical distribution
characteristics in south-subtropical reservoirs during summer, Fe and Mn
concentrations in the water column, as well as the physical and chemical
conditions of the water, were investigated in the lacustrine zones of nine
reservoirs in the eastern of Guangdong Province, in July 2016. These results
showed that Fe and Mn exhibited a strong concentration gradient in deep
reservoirs due to thermal stratification. The total Fe (TFe), total Mn (TMn),
dissolved Fe (DFe), and dissolved Mn (DMn) concentrations in the surface water
are significantly lower than in these in bottom zones (TFe, F=6.708, P=0.032;
TMn, F=9.720, P=0.014; DFe, F=8.129, P=0.029; DMn, F=11.125, P=0.016). The
average concentrations of TFe and TMn are 0.399 mg.L-1 and 0.422 mg.L-1,
respectively at the bottom five of the deep reservoirs, and the dissolved ions
accounted for more than 70% of this concentration. In shallow reservoirs without
thermal stratification, TFe, TMn, DFe and DMn concentrations in surface water are
lower than those measured at bottom of the reservoir, no significant difference
was detected (TFe, F=0.135, P=0.726; TMn, F=0, P=1; DFe, F=0.006, P=0.943; DMn,
F=0.007, P=0.936). The average concentrations of TFe and TMn are 0.110 mg.L-1 and
0.089 mg.L-1, respectively at the bottom of the four shallow reservoirs, and they
were present predominantly in particulate form. The concentrations of TFe and DFe
correlated significantly (P<0.05) with the dissolved oxygen (DO) concentration,
pH and depth, but did not significantly correlate with TN or TP concentration in
the deep reservoirs. The gradient distributions of DO and pH levels is critical
to the gradient distribution of Fe and Mn in deep reservoirs because of water
stratification. Low DO concentrations and acidic conditions in these areas
contributed to the release of Fe and Mn from sediment and result in high
dissociation of these elements in the bottom of deep reservoirs. Simultaneously,
high concentrations of Fe and Mn at the bottom of reservoirs may also attribute
to the characteristic red soil of this region. The results from this study imply
that the high concentrations of Fe and Mn common in the bottom of deep reservoirs
is associated with the stable stratification of these reservoirs in the summer.
The concentrations of Fe and Mn may be exceed water standards when deep water is
taken for public water provision. The problem may be avoided with surface water
supplying.
PMID- 29965398
TI - [Occurrence, Distribution, and Ecological Risk of Antibiotics in Surface Water in
the Liaohe River Basin, China].
AB - The pollution and ecological risk characteristics of five typical antibiotics
found in the surface water of the Liaohe River Basin (LRB) were analyzed and
evaluated using solid-phase extraction and high-performance liquid chromatography
tandem mass spectrometry. These results showed that macrolides have the highest
average concentration of all antibiotics in the surface water of the LRB of
201.88 ng.L-1, followed by quinolones, trimethoprim, and sulfonamides with
average concentrations of 113.40 ng.L-1, 93.93 ng.L-1, and 124.27 ng.L-1,
respectively. Tetracycline demonstrated the lowest concentration at 24.37 ng.L-1.
In addition, antibiotics pollution of the Daliao River is clearly identified as
being higher than that of the Liaohe River, and the highest proportion of
antibiotic pollution (49.1%) is found to come from human use according to a
source apportionme0nt analysis. Relatively high levels of ecological risk are
identified from Trimethoprim and Erythromycin-H2O concentrations, especially for
cities such as Xinmin, Shenyang, and Anshan. The risk assessment indicates that
surface water of the LRB faces high ecological risk and argues for greater
attention to be paid to risk management and pollution controls.
PMID- 29965399
TI - [Effects of Optimized Fish Farming on the Sediment Nutrients of Eastern Lake
Taihu].
AB - The farming of lake fisheries is an important part of the freshwater fishery
industry in China. However, farming patterns of traditional fisheries maintain
serious negative effects on the ecosystem of Eastern Lake Taihu. In recent years,
the enclosure culture model of this lake has been optimized. In order to
investigate the effects of aquaculture on the sediment properties, samples were
collected from different areas of the lake (i.e. within the culture areas,
outside the culture areas; from the crab-plant co-culture areas, mixed culture
areas, ecological restoration areas, and control areas), in different months
(January, March, April, August, and November), and at different depths (0-1 cm
and 9-10 cm). The results of this sampling indicates that 1 the concentrations of
total nitrogen (TN) and total phosphorus (TP) in the sediments samples collected
within the culture areas are slightly higher than samples collected outside the
culture areas; 2 compared to the crab-plant co-culture areas, lower
concentrations of TN and TP are found in the samples collected from the mixed
culture areas; 3 in the ecological restoration areas, aquatic plants exhibit
certain positive effects with decreasing concentrations of TN and TP in the
sediment. The lowest concentrations of TN and TP are detected in the sediment
during the growing season of aquatic plants.
PMID- 29965400
TI - [Responses of the Benthic Diatom Community to Nutrients and the Identification of
Nutrient Thresholds in Three Aquatic Ecoregions of the Huntai River, Northeast
China].
AB - Benthic diatom communities and nutrient gradients were investigated from 287
sampling sites in three aquatic ecoregions (AE) of the Huntai River to
characterize the spatial distribution of nutrients and the benthic diatom
communities. Locally weighted scatterplot smoothing (LOWESS) was used to analyze
the thresholds for nitrogen and phosphorus. The results showed that:1 The
concentration of ammonia nitrogen and total phosphorus significantly differs in
the three AEs, and shows a tendency of AEI < AE II < AE III. 2 To reveal the
structure of benthic diatom communities, various benthic diatom indexes,
including the sportive diatom percentage, sensitive diatom percentage, stipitate
diatom percentage, Pielou evenness index, specific polluosensitivity index (IPS),
biological diatom index (IBD), and generic diatom index (IDG) were analyzed. The
sportive diatom percentage varied significantly in AEI, AEII, and AE III, with
the highest percentage observed in AEIII and the lowest in AEI. However, the
other six indexes exhibited an opposite trend. All revealed that AE III has been
seriously damaged, while AEI is less disturbed than AEII and AE III. 3 LOWESS
fitting curves show thresholds for ammonia nitrogen (NH4+ -N) in the three
aquatic ecoregions as 0.13, 0.30, and 1.98 mg.L-1, respectively and for total
phosphorous (TP) were 0.04, 0.06, and 0.20 mg.L-1. All results were tested by
independent-sample T tests. This study will provide assistance for effectively
protecting the benthic diatom community in different aquatic ecoregions and also
provide a theoretical basis for water management.
PMID- 29965401
TI - [Impacts of Environmental Conditions on the Soaking Release of Nitrogen and
Phosphorus from Cynodon dactylon (Linn.) Pers. in the Water-level Fluctuation
Zone of the Three Gorges Reservoir Region].
AB - The flooding-drying cycles in the water-level fluctuation zone (WLFZ) of the
Three Gorges Reservoir (TGR) result in an abundance of plants that are submerged
and decomposed to release nutrients. This has the potential to lead to water
quality deterioration of the TGR. Cynodon dactylon (Linn.) Pers., one of the
typical plants in the WLFZ, was collected and inundated in the laboratory under
different conditions under temperatures of 15C and 25C, a pH 5.0 to 9.0, and
under light and dark conditions, respectively, to measure the decomposition rate
and nitrogen and phosphorus release mechanisms. The dry weight lost with the
contents of nitrogen and phosphorus was found to decrease after Cynodon dactylon
(Linn.) Pers. was soaked for decomposition. The amount released of total nitrogen
(TN) and total phosphorus (TP) at 25C for 200-days inundation was(2.66+/
0.29)g.kg-1 or(3.76+/-0.04)g.kg-1, respectively and at 15C was(0.79+/-0.03) g.kg
1 or (1.40+/-0.02) g.kg-1, respectively. When the pH of the water submerging the
grass was 5.0, 7.0 and 9.0, the amount of TN released was (3.76+/-0.08) g.kg-1,
(2.66+/-0.29) g.kg-1, and (2.55+/-0.12) g.kg-1, respectively while the amount of
TP released was (1.53+/-0.04) g.kg-1, (0.79+/-0.03) g.kg-1, and (1.70+/-0.07)
g.kg-1, respectively. The TN and TP released was (3.87+/-0.14) g.kg-1 and (1.78+/
0.08) g.kg-1 under dark condition. The lower the temperature, the higher the
amount of TN and TP will be released for inundation from Cynodon dactylon (Linn.)
Pers. When the overlying water is acidic or alkaline, more TN and TP is released.
Dark conditions are beneficial to nitrogen and phosphorus release into the
overlying water. Thus, the water environment changes in each flooding season in
winter. Sewage discharge will also accelerate the nutrients released from soaked
plants through their decomposition in the WLFZ, and then will aggravate the
deterioration of water quality in TGR.
PMID- 29965402
TI - [Effects of Soil Microbial Diversity on the Phosphate Fraction in the Rhizosphere
of Phragmites communis in the Yeyahu Wetland in Beijing, China].
AB - In this research, microorganisms in rhizosphere/non-rhizosphere soils of
Phragmites communis in the Yeyahu Wetland were studied. A sequential extraction
procedure was used to analyze the phosphorus (P) forms in the rhizosphere/non
rhizosphere soil with a variety of plant growth conditions (April, July,
October). The soil bacteria community structure and the diversity was measured
using the high-throughput of 16S rRNA amplicons. Furthermore, the complete
crystallographic analysis (CCA) method was used to analyze the relationship
between phosphate solubilizing microorganisms and P transformation in the soil
samples. The results showed that the rank order of inorganic P (IP) fractions in
the soil was generally as follows:Ca-bound P (Ca-P) > Occluded P (Oc-P) > Fe
bound P (Fe-P) > Exchangeable P (Ex-P) > Al-bound P (Al-P). The IP content was
most affected by the growth of Phragmites communis. The minimum content of IP
appeared in the vigorous growth period and the total IP content in the
rhizosphere soil was generally lower than in the non-rhizosphere soil. The rank
order of organic P (OP) fractions were highly resistant OP (HR-OP) > moderately
resistant OP (MR-OP) > moderately labile OP (ML-OP) > labile OP (L-OP), and all
the components of OP first decreased and then increased with the growth of plant.
The major phylogenic groups in rhizosphere/non-rhizosphere soil of Phragmites
communis, included Proteobacteria, Acidobacteria, Chloroflexi, and Actinobacteria
among which, Proteobacteria was the majority group in the community composition.
Furthermore, the rhizosphere/non-rhizosphere microbial community structure was
significantly affected by seasonal changes and existing differences between the
rhizosphere and non-rhizosphere soils. In addition, the main functional groups of
the modal transformation of P bacteria genera were Bacillus, Enterobacter,
Pseudomonas, Burkholderia, Acinetobacter, which can make use of most OP and IP,
playing an important role in the transformation of P in wetland soils.
PMID- 29965403
TI - [Nitrification and Denitrification Potential of Benthic Sediments in a Suburban
Stream under Intense Human Disturbance Scenarios].
AB - Water and benthic sediment samples were collected monthly from six sites over a 2
km reach in a first-order stream located in the northeastern rural-urban fringe
of Hefei City, from May 2016 to January 2017. These sites were scattered in three
stream reach types as natural pattern sections (Scenario 1), point source
pollution sections (Scenario 2), and severe soil erosion sections (Scenario 3).
The potential rates of nitrification and denitrification in the sediments were
measured and variable characteristics were evaluated quarterly. Moreover, a
difference analysis of each of the three scenarios and an influencing factor
analysis for nitrification and denitrification potentials were subsequently
conducted. Our results show that:1 the mean value of the nitration ratios for
total sediment samples is 0.381%, of which the maximum nitration ratio emerged in
Scenario 2. As for Scenario 1, the nitration ratio in summer is the larger than
in winter. The nitration ratios for Scenarios 2 and 3 rank from largest to
smallest as spring > summer > autumn > winter. 2 The mean value of the
nitrification rate of the total sediment samples is 0.364 mg.(kg.d)-1, of which
the maximum nitrification rate is associated with in Scenario 2. The
nitrification rate is highest in winter, while similar for all other seasons in
Scenarios 2 and 3. There is not much difference all year round for Scenario 1. 3
Average values for the denitrification ratio and denitrification rate for all
sediment samples are 37.25% and 57.68 mg.(kg.d)-1, respectively. Both of these
are higher for Scenario 2 than the other two scenarios for the same season. The
ranking for denitrification for Scenarios 1 and 2 is summer > spring > autumn >
winter, and spring > summer > autumn > winter in Scenario 3. 4 According to the
difference analysis, significant differences not only exist between the
nitrification rates between Scenarios 1 and 2 but also for the denitrification
ratios and denitrification rates between Scenarios 1 and 3. In addition, there is
an obvious difference in the nitration ratio between Scenarios 2 and 3. 5 Partial
least-squares regressive analysis indicates that there is significant difference
between the important influencing factors related to the nitration ratio and
nitrification rate for each of the three scenarios.
PMID- 29965404
TI - [Distribution of External Phosphorus in the Sedimentary Phosphorus forms Under
Different Disturbances].
AB - The distribution of external phosphorus (P) in the overlying water, pore water,
and sediment under different disturbances were investigated and the
transformation between internal P forms was analyzed. The results show that
physical disturbances can promote the migration of external P from the overlying
water to the sediment. In addition, the enhancement was even higher due to the
bioturbation of the combined disturbances. Noticeably, the improvement of the P
migration in the control was lowest, compared with the three disturbances. This
may be attributed to the penetration of dissolved oxygen. Meanwhile, the physical
disturbance reduced the average content of (dissolved organic phosphorus) DIP in
the pore water by 12.13% (a mean of 6d and 10d), compared with the control.
However the reduction was less than that associated with the bioturbation
(38.63%) and the combined disturbance (50.79%), respectively. These three
disturbances may promote the formation of Fe/Al-P and Ca-P. The formation of
Fe/Al-P and Ca-P was largest under the physical disturbance. However, the algal
available phosphorus (AAP) is reduced due to the physical disturbance, suggesting
that physical disturbance may promote the transformation of AAP to occluded Fe/Al
P or Ca-P.
PMID- 29965405
TI - [Effect of Elodea nuttallii-Immobilized Nitrogen Cycling Bacteria on the
Mechanism of Nitrogen Removal in Polluted River Water].
AB - Surface water, Elodea nuttallii and undisturbed sediment cores from the Qinshui
River in Gonghu Bay were collected to carry out a simulation experiment in a
laboratory to study the effect of Elodea nuttallii-immobilized nitrogen-cycling
bacteria on nitrogen removal mechanisms from the river water. In this study, the
transformation and fate of ammonium among four different treatment groups were
investigated by using a stable 15 N isotope pairing technique combined with high
throughput sequencing technology[Treatment A:bare sediment, Treatment
B:sediment+immobilized nitrogen cycling bacteria (INCB), Treatment C:sediment+E.
nuttallii, Treatment D:sediment+INCB+E. nuttallii]. The results of the 15 N mass
balance model showed that there were three pathways to the ultimate fate of
nitrogen:precipitated with the sediments, absorbed by E. nuttallii, and consumed
by microbial processes[denitrification and anaerobic ammonium oxidation
(ANAMMOX)]. The percentages of E. nuttallii assimilated in the 15 NH4+ were
25.44% and 19.79% for treatments C and D. The sediment storage ratio of 15 NH4+
accounted for 7.94%, 5.52%, 6.47% and 4.86% in treatments A, B, C, and D,
respectively. The proportion of 15 NH4+ lost as 15 N-labelled gas were 16.06%,
28.86%, 16.93% and 33.09% in the four different treatment groups, respectively.
Denitrification and anammox were the bacterial primary processes in N2 and N2O
production. The abundance and diversity of microorganisms was relatively higher
in the treatment with E. nuttallii-immobilized nitrogen cycling bacteria (E-INCB)
assemblage technology applied. Furthermore, the removal rates of 15 NH4+ were
24%, 34.38%, 48.84% and 57.74% in treatments A, B, C and D, respectively. These
results show that the E-INCB assemblage technology may improve the capacity for
nitrogen removal from the river water.
PMID- 29965406
TI - [Zero-Valent Iron (ZVI) Activation of Persulfate (PS) for Oxidation of Arsenic
(V) Form Aqueous Solutions].
AB - Arsenic is one of the most toxic substances yet discovered and arsenic
contamination of water has become a global environmental problem in need of a
solution. This study has identified the capacity of sodium persulfate (PS),
activated by zero-valent iron (ZVI) to remove As(V) from waste-water is much
greater than the capacity of PS alone due to the production of sulfate radicals
in the process. Five parameter types including PS and ZVI dosage, reaction
temperature, initial pH value, and initial As(V) concentration are discussed in
detail. These parameters affect the removal rate dynamics as an influencing
factor of the As(V) concentration. The material structure before and after the
reaction was characterized by X-ray photoelectron spectroscopy analysis (XPS) and
scanning electron microscopy (SEM). It was demonstrated that under this solution
of 20-100 mg.L-1 of As(V), the removal rate of As(V) is more than 98% and a
pseudo-second order kinetic model can be used to describe the reaction. The
removal mechanism of ZVI/PS to As(V) was explored by comparing the results of X
ray photo-electron spectroscopy of samples taken before and after reaction with
ZVI/PS. PS can accelerate the corrosion of ZVI and then promote the adsorption of
As(V), moreover, it can also form precipitates and coprecipitates with iron
oxide/hydroxide to achieve an enhanced removal of As(V).
PMID- 29965407
TI - [Removal of Antimony from Water by Nano Zero-Valent Iron/Activated Carbon
Composites].
AB - Nano zero-valent iron/activated carbon (nZVI/AC) composites were prepared via
liquid phase chemical precipitation and then characterized by X-ray diffraction,
X-ray photoelectron spectroscopy, scanning electron microscopy and Brunauer
Emmett-Teller theoretical methods for an analysis of the structure, morphology,
physical and chemical characteristics of the composites. The effects of the
reaction system, nZVI loading, initial pH, and dosage on antimony removal were
investigated and the removal mechanisms were discussed. These results indicate
that nZVI/AC can be successfully prepared via liquid phase chemical
precipitation. In an N2 atmosphere, a dosage of 0.2 g.L-1, 15% nZVI/AC with an
initial pH of 7.5 (the pH of raw water) was prepared. After a reaction duration
of 2 h, the removal rate of Sb(V) had reached 76.2% and the effluent
concentration had decreased to only 23.8 MUg.L-1. These results show that Fe2+
plays a major mechanistic role in the removal of Sb(V) from the system and is the
major active substance in the reaction process. In combination with an analysis
of elemental Sb on the surface of the nZVI/AC before and after reaction, the
removal process relies on the reduction of Fe(0) and Fe2+, Sb(V) reducted into
Sb(III) and through adsorption removal.
PMID- 29965408
TI - [Effect of the Flow Patterns of Main-stream Reactors on the Efficiency of
Nitrification Enhancement with Bioaugmentation].
AB - A nitrifying sequencing batch reactor (SBR) and continuous stirred-tank reactor
(CSTR) were operated at 15C under the same conditions to investigate the effect
of two typical flow patterns (plug flow and complete mixing) on the efficiency of
nitrification enhancement. The results show that, during bioaugmentation, the
ammonia utilized rate(AUR)and nitrite utilized rate(NUR)in the SBR were 2.34 and
2.39 times of that before bioaugmentation, and after bioaugmentation ceased, the
AUR and NUR slightly decreased to 2.01 and 1.78 times of that before
bioaugmentation. Meanwhile, the AUR and NUR in the CSTR were 2.63 and 2.44 times
that before bioaugmentation, and after bioaugmentation ceased, the AUR and NUR
decreased to 1.48 and 1.31 times that before bioaugmentation. Fluorescence In
Situ Hybridization (FISH) results showed that during bioaugmentation, the ammonia
oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) in the SBR were
2.67 and 2.71 times of that before bioaugmentation, and after bioaugmentation
ceased, the AUR and NUR slightly decreased to 2.14 and 1.95 times that before
bioaugmentation. Meanwhile, the AUR and NUR in the CSTR were 2.91 and 1.77 times
of that before bioaugmentation, and after bioaugmentation ceased, the AUR and NUR
decreased to 1.25 and 1.50 times of that before bioaugmentation. Therefore, the
efficiency of nitrification enhancement was similar between the two types of flow
patterns during bioaugmentation, but the seeded nitrifiers were much more
vulnerable to wash out in the CSTR than that in the SBR due to r/K selectivity of
the flow patterns.
PMID- 29965409
TI - [Effect of Temperature on Nitrogen Removal Performance and the Extracellular
Polymeric Substance (EPS) in a Sequencing Batch Reactor (SBR)].
AB - In this paper, the long-term effects of temperature on the nitrogen removal
performance and the extracellular polymeric substance (EPS) in a sequencing batch
reactor (SBR) treating synthetic wastewater was investigated under three
temperature conditions (15C, 25C, 35C). The results showed that high temperatures
(35C) could promote the establishment of short-cut nitrification processes and
improve nitrogen removal performance greatly. Temperature had a significant
impact on the EPS and its composition. With an increased temperature, the EPS and
tightly bound EPS (TB-EPS) content decreased, while, loosely bound EPS (LB-EPS)
increased slowly. TB-EPS became dominant in the EPS (the percentage of TB-EPS/EPS
was 69.0%-79.5%), however, the ratio of TB-EPS/LB-EPS decreased from 3.8 (15C) to
3.6 (25C), and then to 2.2 (35C) with a gradual increase in temperature.
Moreover, protein (PN) and DNA in the EPS, TB-EPS, and LB-EPS decreased with an
increasing temperature. Carbohydrates (PS) in the EPS and LB-EPS increased as
temperature increased, nevertheless, PS in TB-EPS decreased. Furthermore, 25C was
identified as the breaking-point temperature in the variation of PN, DNA and PS
concentrations. At 15C and 25C, PN was the main component in TB-EPS and LB-EPS.
PS has the second highest concentration and DNA the least. However, PS were the
dominant component at 35C, with PN having the second highest concentration, and
DNA having a subtle concentration. Moreover, at 15C and 25C, the EPS content
increased in the nitrification process and reduced in the denitrification
process.
PMID- 29965410
TI - [Effects of Temperature on Shortcut Nitrification and Nitrification Activity of
Nitrification in an Intermittent Aeration Sequencing Batch Reactor].
AB - Real domestic sewage was treated with sequencing batch reactors (SBR). The
aerobic/anoxic modes were alternated 4 times at 30C and 7 times at 18C in a
single-cycle, respectively, and the ratio of aerobic/anoxic cycles was 30 min/30
min. The influent concentration of ammonia and nitrite was 61.44 mg.L-1 and 0.77
mg.L-1, respectively. After the experiments were run for 61 and 90 cycles, the
effluent of the ammonia was 0.68 mg.L-1 and 1.28 mg.L-1 and the removal rate for
ammonia was 98.94% and 99.57%, respectively. The nitrite concentrations were
20.57 mg.L-1 and 20.18 mg.L-1, and the nitrite accumulation rate reached 95.92%
and 99.58%, respectively. During shortcut nitrification, the activity of the
ammonia oxidizing bacteria (AOB) increased gradually before finally stabilizing
at 100.00%, however the activity of nitrite oxidizing bacteria (NOB) increased
first and then decreased gradually, the activity of AOB exceeded NOB at 32 and 74
cycles respectively, where the AOB became the dominant bacteria and the activity
of NOB was completely inhibited at 61 and 90 cycles.
PMID- 29965411
TI - [Nitrite Type Denitrifying Phosphorus Removal Capacity of Cycle Activated Sludge
Technology Processes Under Different Inducing Patterns].
AB - A modified cyclic activated sludge technology (CAST) reactor was utilized to
investigate the phosphorus and nitrogen removal performance under different
inducing patterns in this experiment. The results show that nitrite addition
under anoxic conditions has a more inhibitory effect on the denitrifying
phosphorus removal performance of the sludge. The phosphorus removal performance
of the system was least effective when nitrite dosage was 5 mg.L-1. Compared to
an anoxic addition system, the CAST system is more stable under aerobic addition
conditions. The phosphorus removal properties have a slight fluctuation during
each initial operating condition when the nitrite concentrations are 5, 10 and 15
mg.L-1, respectively. However, the phosphorus removal rate was observed to
recover quickly and remain stable at more than 95% after acclimatizing for 10, 6,
and 34 days, respectively. The effluent phosphorus concentration was less than
0.5 mg.L-1 in all cases. It was also found that the phosphorus removal
performance deteriorated drastically when the nitrite dosage was 20 mg.L-1.
Nevertheless, the nitrite type denitrifying phosphorus uptake capacity of the
sludge was 10.4 times greater than that of the sludge before acclimatizing,
suggesting that the phosphorus performance deterioration due to nitrite addition
could be relieved and long-term addition is beneficial to enriching denitrifying
phosphorus accumulating bacteria using NO2- as an electron acceptor. Moreover,
the sludge settling performance was found to be effective and the sludge
concentration decreased continuously when adding a certain concentration of
nitrite under aerobic conditions, which is of significant for sludge reduction.
PMID- 29965412
TI - [Laboratory-scale CANON Processes Applied to Wastewater Treatment Plants].
AB - A laboratory-scale completely autotrophic nitrogen removal over nitrite (CANON)
process was operated in a municipal wastewater treatment plant (WWTP). Sewage
effluent treated by the anaerobic/oxic (A/O) process and was used to operate a
WWTP to obtain the initial substance for the start-up of a CANON filter reactor.
On the 48th day, the ammonia removal rate was measured at greater than 90% in
successive 10 d samples and the nitrogen removal rate was greater than 70%. The
CANON filter was successful at start up. From the 49th to the 129th day, the
dissolved oxygen in the reactor was maintained at fairly low concentration of 0.2
0.5 mg.L-1. The effluent contained nearly no ammonia and the maximum total
nitrogen (TN) concentration was 15.6 mg.L-1, which exceeded the national Class 1A
Discharge Standards for pollutants from municipal wastewater treatment plants.
Nitrite oxidizing bacteria (NOB) proliferated excessively in the reactor.
Backwash was implemented on 129th, 169th and 213th days. The nitrogen removal
rate was more than 70% for a long time and TN concentration in effluent was below
12 mg.L-1. The nitrogen concentration in effluent fitted the national Class 1A
Discharge Standards and the NOB were effectively inhibited. These results show
that backwash has negligible on the structure of filter and its impact on the
thickness of the bio-membrane and its functional bacteria was small, however, it
is capable of effectively inhibiting the activity of the NOB. Periodically
backwashing can be utilized as an engineering application to maintain stable
operation of the CANON process.
PMID- 29965413
TI - [Effects of Magnetic Activated Carbon with Different Particle Sizes on Sludge
Granulation in a SBR System].
AB - In this paper, 1.5 g.L-1 of magnetic activated carbon with different particle
sizes being 80, 140, 200, and 300 mesh (numbered 2, 3, 4, 5) were inoculated into
the same sequencing batch reactor (SBR). The sludge volume index (SVI), particle
size distribution characteristics, changes of extracellular proteins (PN),
polysaccharide (PS), and polymeric substances (EPS) and their decontamination
capability were studied and compared with a control group without addition
(numbered 1). The results show that different particle diameters of magnetic
activated carbon have certain influences on the granulation process. For example,
it is easier for activated sludge to form aerobic granular sludge (AGS) when
particle size are 140 mesh and 200 mesh acting as an inner core. Under these
conditions, the AGS has a close structure and good sedimentation characteristics.
Gaussian distribution was adopted to analyze the characteristics of Tparticle
size distribution and standard deviations. The average diameter of the sludge in
3# and 4# all reached 780 MUm within 50 days, which was higher than other
reactors, with the same standard deviations being 318.9 MUm and 362.3 MUm
respectively, which is lower than 2# and 3#. Besides, the granular sludge formed
in both reactors was uniform in size and stable in operation. Different particle
sizes of magnetic activated carbon were beneficial for the enhancement of
proteins (PN), especially those with appropriate diameters (140 and 200 mesh),
but had little effects on polysaccharides (PS). The formation of aerobic granular
sludge based-magnetic activated carbon was in accordance with the inert kernel
model. Meanwhile, the PN/PS in 3# and 4# were obviously higher than other SBRs
with the same removal rate of TN and TP reaching 50% and 60% respectively.
PMID- 29965414
TI - [Storage and Reactivation of Anaerobic Ammonium Oxidation (ANAMMOX) Sludge at
Room Temperature].
AB - Slow growth rates limit the widespread application of anaerobic ammonia oxidation
(ANAMMOX) reactions, which presents a need for the study of long-term storage and
rapid reactivation of ANAMMOX sludge. Under room temperature conditions (14~30C),
this study investigated the effects of storage duration on the residual activity
and the activity after reactivation of ANAMMOX sludge without the addition of
external substances. The chosen storage durations were 15, 30, 45, 60, 75 and 100
days, respectively. The results show that the residual specific ANAMMOX
activities (SAAs) of the stored ANAMMOX sludge were 90.9%, 64.3%, 61.7%, 43.2%,
25.8% and 19.3% of the initial activity (activity before sludge storage) after
15, 30, 45, 60, 75 and 100 days, respectively. Therefore, the residual SAA
decreases linearly with an increase in the storage duration of ANAMMOX sludge (R2
was 0.978). The SAAs after reactivation with a storage duration of 15, 30, 45, 60
and 75 days were all higher than the initial SAA and reached 103.4%, 129.3%,
124.8%, 111.7% and 116.9% of the initial SAA before its storage, respectively.
However, the SAA after reactivation after storage for 100 days was just 98.9% of
the initial SAA. In conclusion, after as long as 100 days of storage duration
under room temperature, the residual SAA of ANAMMOX sludge decreases to 0.0513
g.(g.d)-1, and its ANAMMOX activity can still be recovered after 9.5 days of
reactivation culture.
PMID- 29965415
TI - [Microbial Population Dynamics During Sludge Granulation in a Simultaneous
Nitrogen and Phosphorus Removal System].
AB - In this study, domestic sewage was utilized to cultivate aerobic granular sludge
(AGS) in a simultaneous nitrogen and phosphorus removal (SNPR) system. The
bacterial population dynamics during the aerobic sludge granulation were
investigated to reveal the granulation mechanisms using Illumina MiSeq PE300 high
throughput sequencing. Quantitative real time polymerase chain reactions (PCR)
were used to investigate shifts in the abundance of ammonia-oxidizing bacteria
(AOB), ammonia-oxidizing archaea (AOA), nitrite-oxidizing bacteria (NOB) and
polyphosphate accumulating organisms (PAOs). After cultivation for 100 d, the AGS
was compact and demonstrated good SNPR performance. During the AGS formation
process, extracellular polysaccharides obviously increased, while extracellular
proteins kept relatively stable. The abundance of AOA significantly decreased
during the formation of AGS process, while the abundance of PAOs increased. The
bacterial diversity increased at first and then decreased during the formation of
AGS. The bacterial community changed dramatically during aerobic sludge
granulation. Persistent operational taxonomic units (OTUs) accounted for 92.70%
of the total sequences. Proteobacteria (31.07%-53.67%), Bacteroidetes (6.70%
16.50%) and Chloroflexi (7.84%-13.36%) were the dominant phyla. Candidatus
competibacter was obviously enriched in the AGS formation process (increased from
0.11% in the seed sludge to 35.33% in the AGS) and may play an important role in
the formation of AGS.
PMID- 29965416
TI - [Anaerobic Reduction Process Characteristics and Microbial Community Analysis for
Sulfate and Fe(II) EDTA-NO/Fe(III) EDTA].
AB - Based on biological flue gas desulfurization technology (Bio-FGD) and chelating
absorption-biological regeneration technology (BioDeNOx), simultaneous
desulfurization and denitrification by biological methods combined with chelating
absorption technology has been proposed in this study. This technique uses an
alkaline absorption liquid with Fe(II) EDTA to absorb the SO2 and NO in the flue
gas. In this study, an attempt is made to simultaneously remove sulfate (SO42-)
and Fe(II) EDTA-NO/Fe(III) EDTA, which are the SO2 and NO absorption byproducts
in an anaerobic reactor. The results indicate that average removal efficiencies
for SO42- and Fe(II) EDTA-NO of 95.16% and 96.61%, respectively, were achieved
when the hydraulic residence time (HRT) and pH were controlled at 16 h and 7.0.
The reduction products of SO42- were mainly in the form of S2- in the liquid
phase and hydrogen sulfide (H2S) in the gas phase, while the reduction products
of Fe(II) EDTA-NO was N2. The reduction of Fe(III) EDTA could be achieved at all
stages of the operation, however, the reduction rate decreases with a reduction
in the HRT. In the fifth stage, the main sulfate-reducing bacteria (SRB) in the
reactor was Desulfomicrobium, a heterotrophic denitrifying bacteria, Pseudomonas,
and two types of sulfur autotrophic denitrifying bacteria, Sulfurimonas and
Sulfurovum, which coexisted. Two genera of bacteria that can also reduce sulfur,
Thermovirga and Mesotoga, were also identified in the reactor.
PMID- 29965417
TI - [Treatment Efficiency and Microbial Community Diversity in a Magnetic Field
Enhanced Sequencing Batch Reactor (SBR)].
AB - The application of SBR reactors is becoming more common and in order to further
improve the efficiency of their treatment it has been proposed to add a magnetic
field to SBR systems. The effects of different magnetic fields on the degradation
efficiency of conventional pollutants in an SBR was studied. MiSeq high
throughput sequencing techniques were used to analyze the diversity of microbial
communities in activated sludge under magnetic field conditions. These results
show that the addition of a magnetic field improves the performance of a SBR
system to an extent and magnetic induction effects are most obvious at 7*10-2 T.
This is identified through a significant effect on the removal efficiency of
total nitrogen and an increase in the denitrification rate from 65.69% to 85.98%.
It also significantly improves the activity of sludge dehydrogenase and has a
positive effect on the removal of various pollutants. The diversity of microbial
communities in activated sludge under different magnetic field intensities shows
a greater microbial abundance and diversity in the active sludge. The bacterial
domain in the experimental SBR includes 14 phyla, which are mainly Proteobacteria
(25.3%-61.5%), Bacteroidetes (18.6%-46.2%), Actonobacteria (5.3%-47.2%), and
Acidobacteria (0.4%-4.0%). Important denitrification bacteria such as
Rhodoblastus, Paracoccus of alpha-Proteobacteria, Alicycliphilus, Comamonas,
Xenophilus, Acidovorax, Dechloromonas, Thauera of beta-Proteobacteria,
Desulfovibrio of delta-Proteobacteria and Planctomycetes, etc. at a moderate
magnetic induction of 7*10-2 T have a high abundance and there is an internal
relationship between this and an increase in denitrification efficiency.
Polyphosphate-accumulating organisms (PAOs) such as Acinetobacter, Pseudomonas,
Propionicimonas, etc., are present at higher levels under these conditions and
follow the same trends as for the phosphorus removal rates. There is a
correlation between bacterial community structure changes and sewage treatment
efficiency in activated sludge. Applied magnetic fields have a positive effect on
sewage treatment by changing the microbial community structure.
PMID- 29965418
TI - [Molecular Research of Acid-Generating Microbial Communities in Abandoned Ores in
the Waste Dump of an Iron Mine in Anhui Province].
AB - The waste dump of an iron mine in Anhui Province has been abandoned for several
decades. Pyrite in the exposed waste ores is oxidized by acidophiles and large
amounts of metal ions and H2SO4 are released, resulting in the formation of an
acid mine drainage (AMD) lake since 1970s. Besides the lake, there are also some
small-scale AMD adjacent to the newly deposited waste ore. In order to study the
acid generation potential of the waste ore and the related microbial communities,
soil samples were taken from beside the AMD lake (1LL) and small-scale AMD (5J,
5Y, 6-1, 6-2, 6-3) and the physicochemical properties and microbial community of
these samples were analyzed. The results reveal that all of samples were highly
acidic and the pH of the 1LL sample was 2.77, while the other samples were even
more acidic, at less than 2.6. The electrical conductivity (EC) (0.32 mS.cm-1) of
the 1LL sample was obviously lower than the other samples (2.25-7.08 mS.cm-1),
which indicates that the newly deposited waste ore contains higher ion
concentrations. The Fe2+ concentration of the 1LL sample was only 0.80 mg.kg-1
but the other five samples were as high as 2.91-33.40 mg.kg-1. This suggests that
most of the Fe2+ in the 1LL sample has been converted to Fe3+ after long-term
oxidization. High-throughput sequencing results showed that most acidophiles in
1LL sample were Actinobacteria, Acidobacteria and Chloroflexi but the microbes in
the remaining five samples were gamma-Proteobacteria, Firmicutes and Nitrospira.
The iron-sulfur oxidizing bacteria, such as Sulfobacillus, Leptospirillum,
Acidithiobacillus, were scarce in the 1LL sample, while they highly abundant in
the other five samples, which proves that the acid-generation process of the
newly deposited waste ore is strong. However, the reduced iron and sulfur in the
1LL sample has nearly been depleted. Statistical analysis shows that the
microbial composition of the 1LL sample is significantly different to that of the
five newly deposited samples, illustrating that microbial community composition
is remarkably influenced by physicochemical conditions.
PMID- 29965419
TI - [Microbial Community Diversity and Differences in Cellar water of Typical
Rainwater Harvesting Area].
AB - In order to explore the natural change mechanisms for cellar water quality for
typical rainwater harvesting and drinking water surfaces in China, the MiSeq high
throughput sequencing method was used to study the differences between
characteristics of microbial communities and functional diversity regarding
collecting and making use of rainwater. This is achieved through constructing
combined modes of different types of catchment areas and water-storing cellars.
The results of this study show that there is significant differences in microbial
community structure and function. The main factors causing this difference are
heterogeneity of internal and external environmental factors regarding cellar
water. The diversity of microbial community structures in cellar water show
patterns of a large number of rare species and few common species. There are
different significant microbial communities at different water points. The
differences in the functional diversity of microbial communities shows that gene
sequences that encode metabolic functions have significant advantages over other
functional gene sequences, and amino acid, carbohydrate, lipid, energy, vitamin,
terpenoid and polyketide, nucleotide, and glycan metabolism, as well as the
biosynthesis of other secondary metabolites, are the main functional groups that
compose metabolic function. This shows that there are a large number of
microorganisms with relatively specific ecological functions in cellar water and
many active metabolic activities are involved. Cellar water quality can be
improved through combined modes of concrete collecting surfaces and water-storing
cellars for collection and storage of rainwater. The results of the study aim to
deepen the understanding of cellar water microbial community structures and
diversity to be used as a reference for improving water quality and selecting the
water surfaces for rainwater harvesting.
PMID- 29965420
TI - [Impact of the Biodegradation of 6:2 Fluorotelomer Alcohol on the Bacterial
Community Structure of Surface Sediment].
AB - Fluorotelomer alcohol (6:2 FTOH) is a polyfluoalkyl substance that has been
widely used in industry and consumer products in recent years, causing potential
harm to the environment. However, currently the impact of 6:2 FTOH and its
degradation products on microbial communities in sediment is unclear. The purpose
of this study is to explore the impact of the biodegradation of 6:2 FTOH on
bacterial community structures in surface sediment based on gene analysis.
Surface sediment and river water were collected from Hai river, Tianjin, and a
microcosm experiment was performed in the laboratory. The concentration of 6:2
FTOH and its degradation products were analyzed by liquid chromatograph-mass
spectrometry/mass spectrometry (LC-MS/MS). The bacterial community structure was
analyzed by denaturing gradient gel electrophoresis and high-throughput
sequencing. The results showed that 6:2 FTOH could be degraded by microorganisms
(half-life was less than 3 d), producing transient products such as 6:2
fluorotelomer carboxylic acid (FTCA) and 6:2 fluorotelomer unsaturated carboxylic
acid (FTUCA) and stable products such as 5:2 fluorotelomer (FT) ketone, 5:2
fluorotelomer alcohol (sFTOH), perfluorohexanoic acid(PFHxA), perfluoro-n
pentanoic acid (PFPeA), perfluorobutanoic acid (PFBA) and 5:3 polyfluorinated
acid. At different stages of 6:2 FTOH degradation, a change of bacteria and the
predominant population became somewhat different. Based on the experimental
results for 100 d, at the Phylum level, the biodegradation of 6:2 FTOH greatly
increases the abundance of Chloroflexi (+24.8%) and decreases the abundance of
Proteobacteria (-17.8%) and Firmicutes (-15.9%). At the Class level, due to the
biodegradation of 6:2 FTOH, bacteria with notable increases included Anaerolineae
(+19.6%) and delta-Proteobacteria (+4.3%), while bacteria with notable decreases
included epsilon-Proteobacteria (-20.0%), Clostridia (-10.1%), Bacilli (-5.8%)
and gamma-Proteobacteria (- 4.2%). At the Genus level, due to the biodegradation
of 6:2 FTOH, bacteria with notable increases included
Anaerolineaceae_(uncultured) (+19.1%) and Thioalkalispira (+13.3%), while
bacteria with notable decreases included Vibrio (-14.1%), Sulfurimonas (-13.2%),
Bacillus (-5.1%), Sulfurovum (-4.2%) and Fusibacter (-4.1%). These results are
helpful for predicting the response of bacteria to the contamination of
polyfluoalkyl substances and isolating the bacteria capable of the biodegradation
of polyfluoalkyl substances.
PMID- 29965421
TI - [Degradation Process of Exogenous Naphthenic Acids and Their Effects on Microbial
Community Structure in Soil].
AB - Naphthenic acids (NAs) are a natural component of petroleum, which account for
about 2% of severe ecological toxicity in addition to polycyclic aromatic
hydrocarbons. With the growth in demand for energy, a large number of NAs have
leaked into soil environments through oil industry processes, which have caused
enormous potential threats to human health and ecosystems. However, there are few
studies about the degradation process of exogenous NAs and their effects on
microbial community structures in soil. This research explores the degradation
process of NAs and their dynamics in microbial communities in soil by adding a
high concentration of 180 mg.kg-1 of NAs to natural, clean soil with the aid of
liquid chromatography and high-throughput sequencing technologies. This study
found that:1 Natural clean soil has a strong capability to degrade high
concentration of NAs with about 50% of the NAs degraded within 5 days, which
stabilized at 80% after 30 days of the experiment; 2 Pollution with NAs obviously
alters the microbial community structure as the number of specific OTU increased
and were mainly distributed in phylum of unidentified Proteobacteria and
Bacteroidetes; 3 Under high concentrations of NAs, the content of Bacteroidetes
and Acidobacteria phylum and the gamma-Proteobacteria of Proteobacteria phylum
all increased swiftly and were speculated to be a potential agents for NA
degradation, with the relative abundance ratio of Bacteroidetes and Acidobacteria
increasing from 4.2% and 2% to 20.3% and 5.5%, respectively, while a 24.8%
decrease was found in Actinobacteria phylum; 4 This study revealed the
degradation process of exogenous NAs and their effects on microbial community
structure in soil, which provided scientific support for the ecological
restoration of petroleum pollution and further study in this area.
PMID- 29965422
TI - [Identification and Nitrogen Removal Characteristics of the Heterotrophic
Nitrification and Aerobic Denitrification Bacterial Strain DK1].
AB - Nitrogen removal by a newly discovered Pseudomons sp. strain, DK1, isolated from
activated sludge was investigated. Using glucose as a carbon source and a
n(C)/n(N) ratio of five, batch experiments showed that the aerobic
denitrification removal rate was 4.09 mg.(L.h)-1 and 4.43 mg.(L.h)-1 with NaNO3
or NaNO2, respectively. Completely nitrogen removal was achieved when using these
two nitrogen sources. DK1 was also found to heterotrophically remove NH4+ -N at a
rate of 2.32 mg.(L.h)-1 and to carry out anoxic denitrification of a range of
concentrations of NO2- -N (from about 100 to 300 mg.L-1) within a maximum of 36
hours of inoculation. In the presence of both NO3- -N and NO2- -N, DK1 was found
to preferentially denitrify NO3- -N. Simultaneous nitrification and
denitrification (SND) capacity of the DK1 strain was observed when using ammonium
and nitrate or ammonium and nitrite and the corresponding nitrogen removal rates
reached as high as 95.06% and 94.69% within 30 hours of inoculation,
respectively. Ammonium with both nitrate and nitrite resulted in a 100% nitrogen
removal within the same time frame. The ability to achieve SND and to denitrify
both NO3- -N and NO2- -N makes the DK1 strain potentially useful for future
application in nitrogenous wastewater treatment.
PMID- 29965423
TI - [Mercury Release Flux and Its Influencing Factors Under Four Typical Vegetation
Covers at Jinyun Mountain, Chongqing].
AB - In order to reveal the characteristics of mercury release flux and exchange
across the soil/atmosphere interface under different vegetation cover types, four
of these types (evergreen broad-leaved forest, bamboo forest, shrub, and
grassland) were chosen as research samples at Jinyun Mountain National Nature
Reserve, Chongqing, Continuous monitoring of the different vegetation covers,
soil/atmosphere interface, and mercury release flux was conducted, at the same
time as the effects of environmental factors were also considered. Results show
that the annual average Hg emission flux for the four kinds of forest cover have
obvious differences. The overall emission performance of Hg is ranked as:bamboo
forest[17.77 ng.(m2.h)-1] > grassland[17.58 ng.(m2.h)-1] > shrubbery[16.87
ng.(m2.h)-1] > evergreen broad-leaved forest[14.32 ng.(m2.h)-1]. There are
obviously seasonal differences between Hg emission and the four kinds of forested
stands in Jinyun mountain and there are significant differences among the
different forests. These differences mainly reflect that emissions in the warm
season are higher than in the cold season. There is also an obvious diurnal
variation of soil mercury release flux from different forested stands in Jinyun
Mountain. Meteorological factors of light intensity, air temperature, soil
temperature, and relative humidity also effects the soil/air interface meaning
that mercury flux is not the same across land cover types. Temperature is the
main factor affecting evergreen broad-leaved forest, shrub forests, and bamboo
forests. Light intensity is the main influencing factor for grasslands.
PMID- 29965424
TI - [Short-term Effects of Nitrogen Deposition on CO2 and CH4 Fluxes from Wetlands in
the Minjiang River Estuary].
AB - In order to evaluate the effects of nitrogen deposition on CO2 and CH4 fluxes
from a Cyperus malaccensis marsh in the Min River estuary at Daoqingzhou, Fujian,
static chamber-gas chromatography (GC) techniques were used. CO2 and CH4 fluxes
at a control (CK)[0 g.(m2.a)-1], N1[24 g.(m2.a)-1], N2[48 g.(m2.a)-1], and N3[96
g.(m2.a)-1] were measured and analyzed and the related environmental factors were
recorded. The results show that,1 compared to the control treatment, the effects
of nitrogen deposition on the CO2 fluxes for N1 and N3 increased by 20.30% and
4.06%, respectively, whereas the CO2 fluxes for N2 reduced by 10.05%,
furthermore, the CO2 fluxes under different treatments were not significantly
different (P>0.05), except for the N2 and N3 treatments in December (P<0.05). 2
Compared to the control treatment, the effects of nitrogen deposition on CH4
fluxes at N1, N2, and N3 were increased by 64.51%, 30.23%, and 80.57%,
respectively, whereas the CH4 fluxes under different treatments were not
significantly different (P>0.05). 3 There was significant positive correlation
between CO2 and CH4 fluxes and soil temperature (P<0.05), however, the CO2 and
CH4 fluxes were not significant with regards to soil pH and soil EC (P>0.05).
PMID- 29965425
TI - [Effects of Plastic Film Mulching on Methane and Nitrous Oxide Emissions from a
Rice-Rapeseed Crop Rotation].
AB - A field experiment was conducted in the Key Field Station for Monitoring of Eco
Environment of Purple Soil of the Ministry of Agriculture of China in the farm of
Southwest University in Chongqing. Static opaque chamber and gas chromatography
methods were used to study the effect of plastic film mulching on CH4 and N2O
emissions characteristics from a rice-rapeseed crop rotation in situ for one
year. The results showed that CH4 and N2O emissions are mainly concentrated in
the early stages of the growth of each crop and there is a clear seasonal
variation of CH4 emissions during the rice growing period and N2O in the rapeseed
growing period. The CH4 flux changed from -0.45 to 1.90 mg.(m2.h)-1 and the N2O
flux varied between -46.1 and 2040.7 MUg.(m2.h)-1 over the entire year. Plastic
film mulching was found to increase the total emissions of CH4 and N2 O, with the
total CH4 emission of(27.22+/-4.48) kg.hm-2 over the entire year, which is 26.22%
higher than that of the non-mulching treatment(19.93+/-0.56) kg.hm-2. The total
amount of N2O emissions under film mulching treatment increased 16.6% from
(11.27+/-2.77) kg.hm-2 under no mulching treatment to (13.14+/-0.82) kg.hm-2. The
results analyzed for soil moisture and soil temperature showed that mulching
significantly increased the soil moisture during the rapeseed season, while there
was no obvious correlation with soil temperature (at depths of 5 cm and for the
surface temperature) for each crop season. During the rapeseed growing season,
CH4 and N2O emissions negatively correlated with soil moisture and has a
significant negative correlation during the seedling period with film mulching
treatment. Moreover, under the two treatments, the correlation between CH4 and
N2O emissions and soil temperature was negligible. This study indicates that
plastic film mulching impacts CH4 and N2O emissions at different growth stages of
the crops, which changes the proportion of the emission of the two gases over the
whole growth period, and promotes the emission of CH4 and N2O in the rice
rapeseed system. In the time scale of 100 years, the integrated global warming
potentials (GWP) of CH4 and N2O emission under plastic film was a CO2 equivalent
of 4213.00 kg.hm-2 compared with that under conventional treatment of 3454.17
kg.hm-2. Conventional emits 22.0% less CO2, indicating that plastic film mulching
is not an effective measure for carbon sequestration.
PMID- 29965426
TI - [Assessment of Pollution, Sources, and Risks of Polycyclic Aromatic Hydrocarbons
in Soil from Urban Parks in Xi'an City, China].
AB - A total of seventeen surface soil samples were collected from urban parks in
Xi'an city. The concentration of sixteen priority polycyclic aromatic
hydrocarbons (PAHs) were analyzed by high performance liquid chromatography
(HPLC). In addition, the composition, source, pollution level and a risk
assessment of PAHs in surface soil of park were evaluated. The results showed
that the total concentrations of sixteen PAHs ranged from 0.362 to 1.336 MUg.g-1,
with a mean value of 0.591 MUg.g-1. The concentration of seven carcinogenic PAHs
(Sigma7CPAHs) ranged from 0.051 to 0.528 MUg.g-1, with a mean value of 0.181
MUg.g-1. Compared to the SigmaPAHs levels of other cities of China, the SigmaPAHs
in park surface soils in Xi'an are relatively low. PAHs in the soil samples were
dominated by low molecular weight PAHs with 2 and 3 rings. The results of source
analysis showed that the PAHs in park surface soil mainly originated from the
combustion of fossil fuels, however, the source of PAHs in some samples is
complex and from mixed sources, such as oil spills, oil burning, and incomplete
combustion of coal and biomass. The ecological risks of PAHs in the surface soil
were evaluated according to the soil quality guidelines to be ERL (effects range
low) and ERM (effects range median), and these results showed that all samples,
in general, were polluted. However, the potential ecological risks of PAHs were
at a low level. The incremental life cancer risk (ILCR) assessment indicated that
health risks for children and adults were both in a permissible range, however,
the risks for children exposed to the soil were considerably higher than for
adults. Dermal contact was the main exposure pathway that resulted in the
relatively higher risk, followed by ingestion.
PMID- 29965427
TI - [Spatial Distribution of Soil Particles and Heavy Metals Under Different
Psammophilic Shrubs in the Ulan Buh Desert].
AB - Aeolian sandy soil was collected at depths of 0 to 100 cm at intervals of 0-10, >
10-20, > 20-30, > 30-40, > 40-60, > 60-80, and > 80-100 cm from under the cover
of psammophilous shrubs Ammopiptanthus mongolicus, Hedysarum scoparium, Oxytropis
aciphylla, Nitraria tangutorum and Haloxylon ammodendron and from a mobile dune
in the Ulan Buh Desert. Multi-fractal theory was used to determine the soil
particle size distribution (PSD), which measured the fractions of omega(Mn),
omega(Zn), omega(Cr), omega(Cu), omega(Pb), omega(Ni), omega(As), and omega(Cd),
as well as their distribution status in the laboratory and analyzed correlations
between the PSD and heavy metal content to identify the relationship between soil
structure and heavy metal pollution. This result shows that a range of different
types of shrubs can increase the distribution of fine soil particles, and
specifically Ammopiptanthus mongolicus and Hedysarum scoparium can increase
range, heterogeneity and degree of dispersion of the PSD. The heavy metal content
in the soil under the different shrubs is ranked as omega(Mn) > omega(Zn) >
omega(Cr) > omega(Cu) > omega(Pb) > omega(Ni) > omega(As) > omega(Cd). In the
first 10 cm of the soil under the shrubs, the concentration of all heavy metals
are higher than samples from the mobile dune except for Cr and Cu. Average value
of omega(Mn) and omega(Cd) is 354.899 and 1.429 mg.kg-1 under Ammopiptanthus
mongolicus and Hedysarum scoparium respectively. Concentrations of Mn and Cd
under Ammopiptanthus mongolicus and Hedysarum scoparium shrubs are significantly
higher than those of mobile dune (P<0.05), and the concentration of both is
significantly various between each soil layers (P<0.05). The highest value for
omega(Mn) is in soil layer between 30 and 40 cm below the surface and the highest
for omega(Cd) appears between 10 and 20 cm below the surface. The average
omega(Pb) under Hedysarum scoparium is 13.556 mg.kg-1 which is the highest among
all the shrubs, exceeding 3.24% under Ammopiptanthus mongolicus and higher than
samples from mobile dune. However, average omega(As) under Hedysarum scoparium is
exceeded 0.37% under Ammopiptanthus mongolicus but still higher than samples from
mobile dune. The grain size of phi(silt) and phi(medium coarse sand) are
determining factors for heavy metal concentrations in fine and coarse particles
of aeolian sandy soil. Heavy metal measurements all positively correlate with
phi(silt) and phi(clay), however, they negatively correlate with phi(medium
coarse sand), except for omega(Cr). The correlation coefficients between heavy
metal contents and the multifractal parameters are similar for phi(clay),
phi(silt), and phi(medium coarse sand). Therefore, multifractal parameters can
describe the correlation between heavy metals and their determinant soil grain
size. This study shows that, Ammopiptanthus mongolicus and Hedysarum scoparium
can entrap and deposit fine particles from the sand flow to surface soil layers
around shrubs and improve the condition of PSDs for different soil layers with
respect to heavy metals. Hence, in aeolian sandy soil these concentrations are
higher than for mobile dunes after planting Ammopiptanthus mongolicus and
Hedysarum scoparium. Therefore both should be used to promote good soil structure
of particular areas to entrap and in-situ control heavy metals to decrease heavy
metal pollution in downwind cities.
PMID- 29965428
TI - [Effects of UV-B Radiation on Soil Carbon and Nitrogen Transformation under
Different Soil Moisture Contents from Two Paddy Fields].
AB - Carbon and nitrogen in soils play an important role in the global carbon and
nitrogen cycle. The enhancement of ultraviolet radiation (predominantly UV-B)
resulting from the depletion of stratospheric ozone has raised significant
concern. The effects of UV-B radiation on soil carbon and nitrogen transformation
is connected directly to the physical and chemical properties of the soil. In
order to clearly understand the effects of soil moisture on UV-B radiation, this
study collected soil samples from two paddy fields with different levels of
organic matter in a subtropical region of China. The response of the total
organic carbon (TOC), dissolved organic carbon (DOC), ammonia nitrogen (NH4+ -N),
nitrate nitrogen (NO3- -N) and cumulative net nitrogen mineralization to UV-B
radiation under three different moisture gradients (W1=25%, W2=50%, and W3=100%)
were monitored in laboratory for 120 h. After this period, the results were
compared with a control treatment (CK) and it was found that:the TOC content had
significantly decreased under UV-B radiation (p<0.05). From low to high moisture
content (W1, W2 and W3), the TOC decreased by 9.9%, 4.5% and 6.3%, respectively
for soil with low organic matter (L), and by 10.9%, 5.6% and 6.3%, respectively
for soil with high organic matter (H), under UV-B radiation. However, UV-B
radiation was found to enhance the DOC content in the soil compared with the CK.
Furthermore, the DOC for soil moisture contents under 100% (W3) was higher than
for other moisture contents (W1, W2). The measured DOC increased by 21.5% (W1),
9.4% (W2), and 26.3% (W3) for soil with L. In addition, the measured DOC
increased by 26.7% (W1), 14.2% (W2) and 33.8% (W3) for soil with H under UV-B
radiation after 120 h. Compared with control treatment (CK), UV-B radiation
decreased the NH4+ -N content significantly, but there was an increased NO3- -N
content. The decrease of the NH4+ -N content was largest for W3 and smallest for
W1. The increase in NO3- -N content was largest for W2 and smallest for W1 for
the two soil samples under UV-B radiation. UV-B radiation demonstrated an obvious
effect on the cumulative net nitrogen mineralization (p<0.05) after 24 h compared
with the CK and the effect of different soil moisture treatment was also
significant (p<0.05). Overall, light degradation played a major role in the
stabilization of soil organic matter, soil moisture, and UV-B radiation could
accelerate the loss of soil organic carbon and has a major impact on the
transformation of mineral nitrogen in the soil. Therefore, in agricultural
production systems, completely bare surfaces should be avoided. For example,
paddy rice-upland crop rotation systems could reduce the use of fallow periods.
PMID- 29965429
TI - [Various effects on the Abundance and Composition of Arbuscular Mycorrhizal
Fungal Communities in Soils in Karst Shrub Ecosystems].
AB - Slope position is a key factor used in the restoration of vegetation in degraded
karst ecosystems, and arbuscular mycorrhizal fungi (AMF) play an important role
in improving this plant growth. However, little information is available
regarding the effects of slope position on arbuscular mycorrhizal fungi. To test
whether these fungal communities are impacted by slope position, the abundance,
and composition of soil, AMF communities along the slope position were analyzed
through terminal restriction fragment length polymorphism (T-RFLP) and real-time
fluorescence-based quantitative polymerase chain reaction (real-time PCR). The
diversity, richness, and evenness of plant species were evaluated through field
surveys and soil properties were also measured. The results show that content of
carbon, nitrogen, and phosphorus in the soil are different along the slope, and
the trends identified were that the upper slope position ~ middle slope position
> lower slope position. The trend for AMF abundance was identified as upper slope
position ~ middle slope position < lower slope position. The available phosphorus
content in the soil correlated significantly with the AMF abundance. A redundancy
analysis showed that the structure of soil, AMF, and plant community compositions
differed along the slope. The plant evenness index was shown to significantly
contribute to the distribution of the AMF community structure, while the total
nitrogen and total organic carbon content of the soil had a significant effect on
the plant community structure. These results indicate that the interaction
effects of soil nutrients and plant community structures on the soil AMF
community structures suggest micro-morphology should be taken into account when
AMF is used to restore vegetation in karst regions.
PMID- 29965430
TI - [Remediation of Cd/Ni Contaminated Soil by Biochar and Oxalic Acid Activated
Phosphate Rock].
AB - Taking soil contaminated with a combination of Cd and Ni as the research
objective, biochar, and oxalic acid activated phosphate rock (APR) were applied
both together and separately for the remediation of this contaminated soil. The
effects of different ratios of amendments on the remediation of Cd and Ni heavy
metals in the soil and on inorganic nitrogen and microbial biomass nitrogen (MBN)
in the soil were compared. The results show that an increasing amount of biochar
and APR, increases the soil pH gradually and acid-extractable Cd and Ni are
gradually transformed into reducible, oxidable and residual Cd and Ni, resulting
in a reduction in Cd and Ni bioavailability. After 40 days incubation, the acid
extractable Ni decreased by 37.04% with a 14.8% increase in residual Ni, and acid
extractable Cd decreased 40.28% with a 35.20% increase in residual Cd with the
amendment of C50P3 (Applying 50 g.kg-1 biochar and 3 g.kg-1 APR) when compared to
C0P0 treatment (Applying nothing). Furthermore, the MBN content for C50P0
(Applying 50 g.kg-1 biochar only) and C0P3 (Applying 3 g.kg-1 APR only) increased
by 1.5 and 1 times, respectively, while the content of ammonium nitrogen
decreased by 12.5% and 6.4%, respectively and the content of nitrate nitrogen
decreased by 11.6% and 10.2%, respectively. This comparison shows that the
combined effect of the application of biochar and APR is superior to each
respective separate treatment. A mixture of 50 g.kg-1 of biochar and 3g.kg-1 of
APR (C50P3) demonstrates the best effect on the remediation of the Cd and Ni in
soil. Furthermore, the application of amendments promoted the transformation of
inorganic nitrogen into organic nitrogen.
PMID- 29965431
TI - [Effects of Repeated Freezing and Thawing and High Temperature Aging on the
Solidification and Stabilization of Arsenic Contaminated Soil].
AB - The impact of solidification and stabilization effects on arsenic (As)
contaminated soil before and after repeated freezing and thawing or high
temperature aging was investigated by tests of unconfined compressive strength
(UCS), permeability, leaching concentration and fractionation. The microstructure
appearance of the soil was observed using SEM. The results show that the UCS of
solidified soil decreases and its permeability increases after repeated freezing
and thawing or high temperature aging. In stabilized soil, the unstable species
of As increase and the leaching concentration of As rises accordingly after both
treatments. The concentration of unstable species of As increased accordingly by
19.81% and 25.1%, and the leaching concentration rose from 115.5 MUg.L-1 to 151.5
MUg.L-1 and 164.5 MUg.L-1 respectively after 300 freeze-thaw treatments or under
10 h of high temperature aging under 80C. In general, the influence of the
effects increases with more freeze-thaw events and higher temperature aging of
longer duration. More damage and fragmentation was observed after both
treatments.
PMID- 29965433
TI - [Interactions between Goethite and Humic Acid and the Stability of Goethite-Humic
Acid Complex].
AB - Goethite-humic acid complex was prepared in a suspension containing goethite and
humic acid. X-ray diffraction (XRD) results showed that the crystal structure of
this complex had no obvious changes compared to pure goethite, but the peak
intensity of the complex was slightly reduced. Transmission electron microscopy
(TEM) images indicated that the surface of the goethite was coated by particles
of humic acid. Compared to the infra-red (IR) spectra of goethite and humic acid,
the anti-vibrational frequencies of COO- and the vibrational frequencies of =Fe
OH decreased by 20 cm-1 and 9 cm-1, respectively, while the vibrational
frequencies of the associated hydroxyls increased by 10 cm-1 and the absorption
band of carboxylic C-O and free hydroxyls almost disappeared. This indicates that
the interactional mechanisms between goethite and humic acid include the
monodentate coordination of Fe(III) -carboxylate and hydrogen-bonds.
Thermogravimetry/differential thermogravimetry (TG/DTG) analysis showed that the
temperature of the weight loss peak for =Fe-OH in goethite and the complex were
258C and 276C, respectively. This indicates that the coating of humic acid
enhances the heat stability of =Fe-OH in goethite. Compared with humic acid, the
temperature of the weight loss peak for aliphatic organics and aromatic organics
in complex decreased by 60C and 26C, respectively and the ratio of weight loss
from aliphatic organics to aromatic organics in complex increased. This indicates
that organics with a lower heat stability may be more easily adsorbed onto
goethite and the affinity to goethite was higher for the aliphatic organics than
for aromatic organics. After ultrasonic dispersion, the content of large
particles (>= 2 MUm) decreased significantly for both goethite and humic acid,
but the content and the size of large particles in the complex changed only
slightly.
PMID- 29965432
TI - [Evaluation of the Combined Removal of Heavy Metals by Saponin and Citric Acid
from Municipal Sewage Sludges and Metal Stability Features].
AB - Sewage sludge contains a high level of nutrients, such as nitrogen, phosphorus,
potassium and organic matter, with a high recovery value. The presence of heavy
metals in sludges has become a major limiting factor in the utilization of these
sludges. Therefore, the removal of heavy metals before land application of sewage
sludge has become very necessary. Two municipal sewage sludges (S1 and S2) were
collected from municipal wastewater plants in Wuhan city and were studied by
oscillation leaching experiments with combination of saponin and citric acid to
evaluate their removal efficiencies for Cu, Pb and Zn at different volume ratios
(20:1-1:20), ratios of solid to liquid (1:20-1:80), reaction times (0-2880 min),
and leaching times (1-4). The heavy metal fractions in the sewage sludges were
analyzed before and after leaching to study changes in the stability and mobility
of heavy metals by calculating a stability factor[relative bonding strength of
heavy metals (IR)] and a mobility factor (MF). The results show that the highest
removal efficiency of Cu, Pb, and Zn was 43.16% (S1), 32.45% (S2) and 38.69%
(S1), respectively under the removal conditions of a volume ratio (saponin:citric
acid) of 5:1, solid-liquid ratio of 1:60, and leaching time of 1440 min. The
removal efficiencies of Cu and Pb were significantly enhanced and Zn had a small
increase with longer leaching times, which was significantly different after two
to three washing times. The highest removal rate of Cu, Pb, and Zn was 78.89%
(S1), 77.08% (S2) and 49.39% (S1) after four washing times, respectively. Beyond
acid soluble and reducible fractions, other forms of heavy metals have very low
removal rates after a single leaching. The removal rates of heavy metal fractions
increased by increasing the leaching time, particularly for Pb, which in the
residual fraction was significantly increased. The stability and mobility of
heavy metals changes after each leaching. For example, the IR of Cu, Pb, and Zn
increased to 43.63% (S1), 39.44% (S2) and 32.00% (S1), respectively, and the MF
of these heavy metals decreased from 30.19% to 79.45% in the sewage sludges after
four washing events.
PMID- 29965434
TI - [Contents and Health Risks of Organic Phosphorus Esters in Plastic Runway
Products].
AB - Using ultrasonic assisted extraction, column chromatograph purification and gas
chromatograph-mass spectrometer(GC-MS) analysis method to quantify the contents
of seven kinds of organic phosphorus ester(OPEs) in plastic tracks in Chengdu
City. The recovery rates of this method ranged from 71.41% to 110.58% and the
correlation coefficient (r) of the standard curve was higher than 0.99, which
demonstrates satisfying quality control. Plastic track samples were collected
from twelve schools in Chengdu. The results show that OPEs are detected in two
thirds of plastic track samples. TnBP[Tri-n-butyl phosphate] and TEHP[tris(2
ethylhexyl) phosphate] were detected with high frequency, while TCEP[tri(2
chloroethyl) phosphate], TDCPP[tridichloropropyl phosphate] and TPhP[triphenyl
phosphate] were not detected in any samples. Contents of the total OPEs
(Sigma7OPEs) in the plastic track ranged from ND to 534.89 ng.g-1. TnBP was
identified at the highest content levels (ND-462.18 ng.g-1). TCPP[Trichloropropyl
phosphate], a chlorinated phosphate with higher toxicity, was detected in one
sample with a contents of 205.94 ng.g-1. The average exposure dose for adults was
0.14 ng.(kg.d)-1, lower than that for children of 0.64 ng.(kg.d)-1. Risk
quotients of OPEs for adults and children were only 10-7 -10-5 and could be
ignored. These results indicate that the government should limit the consumption,
as well as the type of OPEs which are added to plastic tracks, to protect
population health.
PMID- 29965435
TI - [Effects on Physico-chemical Parameters of Glycoside Hydrolase Family 6 Genes
During Composting of Agricultural Waste].
AB - Polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) was
used to study the changes of glycoside hydrolase family 6 (GH6 family) genes
during the composting of agricultural waste. In addition, a redundancy analysis
(RDA) and Monte Carlo permutation test were applied to determine the relationship
between the changes to the GH6 family genes and physico-chemical parameters.
According to the relative magnitudes of the influence caused by these different
parameters on the changes to GH6 family genes, the eight-ranked physico-chemical
parameters were pH > pile temperature > total nitrogen (TN) > total organic
matter (TOM) > C/N ratio > moisture content > ambient temperature > water soluble
carbon (WSC). The eight physico-chemical parameters, which explained 83.1% of the
variation of GH6 family genes, confirmed that these parameters had important
effects on the GH6 family genes changes. The pH (P=0.002), pile temperature
(P=0.004), and TN (P=0.004) had the most significant impacts on these changes.
These three significant factors explained 24.92%, 15.57%, and 15.04% of the
variation of GH6 family genes, respectively. There were different dominant
species which contain GH6 family genes in different stages of composting. The
diversity and abundance of GH6 family genes demonstrated these fluctuation
trends. The t-value biplots based on the RDA showed that these three significant
factors had either positive or negative correlations with the dynamic changes of
GH6 family genes and the microbial species contained within GH6 family genes can
be generally be divided into five types. The microbial community changes are
reflected by the No. 4 to No. 10 bands and these had a significant positive
correlation with pile temperature and a significant negative correlation with pH
and TN. The microbial community changes reflected by the No. 20 to No. 23 bands
had a significant positive correlation with pH and TN.
PMID- 29965436
TI - [Effect of the Food to Mass Ratio and Hydraulic Retention Time on Hydrogen
Production from Fruit and Vegetable Waste].
AB - Semi-continuous biogas production from fruit and vegetable waste by medium
temperature anaerobic fermentation was conducted. Hydrogen production under
different food-microorganism ratios (F/M 0.5, 0.75, 1.0, 1.5) and hydraulic
retention times (HRT) (2, 3, 4 d) were investigated. The results show that in the
case of a smaller F/M values (0.5 and 0.75), not all HRT stages were conducive to
the continuous production of hydrogen, however, they were conducive to producing
methane, especially when HRT was 3 or 4 d. Continuous hydrogen production was
viable when the F/M ration was relatively higher (1.0 and 1.5), however, this was
not conducive to the production of methane, with almost no methane production
detected in this process. A F/M of 1.0 and a HRT of 3 d provided the best
conditions for continuous hydrogen production from fruit and vegetable waste.
Meanwhile, the highest and average daily volume of hydrogen production were 451.2
mL.(L.d)-1 and (186+/-29) mL.(L.d)-1 respectively, whereas the highest and
average hydrogen production rate of volatile solids were 133 mL.g-1 and (27+/-5)
mL.g-1 respectively. The hydrogen content was 20%-30%.
PMID- 29965437
TI - [Comment on Sensitivity Analysis Methods for Environmental Models].
AB - Environmental models have been regarded as a key method to study the complex
conditions of environmental systems. Sensitivity analysis (SA) is a vital step,
which aims to investigate the impact of model inputs on model outputs. During the
application of environmental models, SA plays a significant role in simplifying
the model structure and improving the precision and reliability of the
simulation. Consequently, identification and analysis of sensitivity parameters
in environmental models is an important issue. This paper provides an
introduction to the functions of SA in environmental models. Mathematical
theories and methods used for SA are summarized, and their applications,
advantages, and limits. On this basis, development trends for the use of SA for
environmental models are proposed.
PMID- 29965438
TI - [Characterization and Variation of Organic Carbon (OC) and Elemental Carbon (EC)
in PM2.5 During the Winter in the Yangtze River Delta Region, China].
AB - Two hundred seventy-nine PM2.5 samples were collected from January 9, 2015 to
January 31, 2015 in Lin'an, Nanjing, and Suzhou. They were analyzed for organic
carbon (OC) and elemental carbon (EC) following the thermal/optical reflection
protocol. The pollution characteristics of OC and EC in PM2.5 during the winter
in the Yangtze River Delta were discussed in detail.The average mass
concentrations of PM2.5 in the three sample sites were (123.56+/-61.11),
(144.77+/-62.91), and (156.5+/-68.97) MUg.m-3, respectively, which were in excess
of the Ambient Air Quality Standard (GB 3095-2012) 24-hr mass-based standard of
75 MUg.m-3. The average mass concentration of OC and EC were (21.93+/-11.69)/(6+/
3.6), (20.32+/-10.3)/(5.39+/-3.07), and (27.08+/-14.35)/(6.4+/-4.29) MUg.m-3,
respectively. Lin'an, which is regarded as the background site for the
atmospheric environment in the Yangtze River Delta, is also polluted seriously.
The OC was strongly correlated with EC in Lin'an (R2=0.83), Nanjing (R2=0.72),
and Suzhou (R2=0.72). This shows that the carbonaceous aerosols have similar
sources during the winter in the Yangtze River Delta. All of the samples' OC/EC
ratios exceeded 2.0, with the sample OC/EC ratios mainly distributed in the range
of 2.5-6.0, indicating that coal combustion and vehicle exhaust are the main
sources of OC and EC. The estimated mass concentrations of SOC were (9.23+/
5.26), (6.82+/-4.36), and (12.56+/-7.52) MUg.m-3, respectively, which contributed
42%, 34%, and 46% to the OC, indicating that SOC is an important part of OC.
Backward-trajectory shows that the mass concentrations of PM2.5, OC, and EC have
a good correlation with the transmission path of the main air mass. The mass
concentrations of PM2.5, OC, and EC controlled by the air mass from poor air
quality areas are 1.14-1.7 times, 1.55-2.1 times, and 1.94-2.47 times higher than
that in the air mass from good air quality areas.
PMID- 29965439
TI - [Important Effect of Secondary Inorganic Salt Extinction on Visibility Impairment
in the Northern Suburb of Nanjing].
AB - Observed data regarding the visibility and aerosol chemical composition from May
2013 to May 2014 were used to analyze the variation of visibility, the
relationship between aerosol chemical composition and visibility variations, and
their contributions to atmospheric light extinction. An important effect of
secondary inorganic salt extinction on the visibility impairment was determined.
The present study suggests that the average visibility during the observation
period was (6.78+/-3.68) km, and there was obvious seasonal variation in the
visibility. Fine particles with size less than 2.1 MUm have a great influence on
visibility, with the main chemical components of SO42-, NO3-, NH4+, and OC. The
secondary inorganic ions make significant contributions to visibility
degradation. The mean light extinction coefficient of Nanjing was (527.2+/-295.2)
Mm-1, which was calculated by using the revised IMPROVE equation. Regarding the
chemical composition of PM2.1, the most contributive species to the light
extinction coefficient were ammonium sulfate, ammonium nitrate, and organic
species, which accounted for 80.6%. Although the light extinction contribution of
organic matter was as high as 43.51% on a clear day (VR>10 km), with the decrease
of visibility, the extinction contribution of organic matter decreased, but the
contribution of secondary inorganic salt increased. The contribution of
extinction was 58.96% for heavy haze days with low visibility (VR<5 km). This
proves that the secondary inorganic salt extinction plays a significant role in
visibility impairment.
PMID- 29965440
TI - [Day-Night Differences and Source Apportionment of Inorganic Components of PM2.5
During Summer-Winter in Changzhou City].
AB - To investigate the day-night variation characteristics of inorganic components in
atmospheric aerosol, PM2.5 samples were continuously collected for one month in
Changzhou during summer and winter. Eleven water-soluble ions (WSIIs) and 13
metal elements were compared in terms of their day-night character and sources.
The results indicated that the day time average PM2.5 mass concentration was
higher than the night time, while the percentage of the total WSIIs in PM2.5
during the night was higher. The total WSIIs fractions in PM2.5 were higher in
winter (44%-45%) compared to summer (31%-36%), with an opposite seasonal
character for metal elements (winter day 3.03%, winter night 2.29%, summer day
4.40%, summer night 4.51%). SO42-, NO3-, and NH4+, were the three main secondary
ions, comprising 77%-85% of the total WSIIs, suggesting that air pollution in
Changzhou exhibits complex pollution characteristics dominated by secondary
processes. The day time SO42-/WSIIs ratio (49.0%) was slightly higher than that
of the night (41.1%) due to the photochemical reaction under stronger solar
radiation, while the lower NO3-(1.98 MUg.m-3) in the day compared to the night
(5.10 MUg.m-3) was attributed to the decomposition of NH4NO3 during summer days.
A good linear correlation among NH4+, SO42- and NO3-, accompanied by a ratio of
predicted NH4+ to measured NH4+ near 1, illustrated that NH4+ ions mainly existed
in the form of (NH4)2SO4, NH4NO3, and NH4Cl. It was concluded from the ion
balance that PM2.5 was weakly alkaline in summer but neutral in winter. Fe, Al,
and Zn were the largest contributors to the total metal elements, with higher
concentrations of Fe and Al and lower levels of Zn in the day time. A correlation
coefficient analysis and principle component analysis revealed that inorganic
components come from sources that include secondary aerosol formation, suspended
dust, and vehicle emissions, but there is some seasonal variation and day-night
differences.
PMID- 29965441
TI - [Characteristics of Elements in PM2.5 and PM10 in Road Dust Fall During Spring in
Tianjin].
AB - To explore the element pollution characteristics and sources of road dust fall,
road dust fall samples were collected during spring in Tianjin and suspended to
obtain PM2.5 and PM10, 16 elements were analyzed, and then their characteristics,
sources, and similarities were studied by nonparametric tests, the coefficient of
divergence, and enrichment factor. The results showed that the mass fraction (1%
20%) in sequential order of the elements in PM2.5 and PM10 in Tianjin road dust
fall were Si > Al > Ca > Fe > Mg > K > Na. The coefficient of divergence of
elements in PM10 and PM2.5 was 0.06, indicating that the elements profiles of
PM10 might be similar to PM2.5. The elements of Cd and Cr in PM10 and PM2.5 were
at a high level of enrichment degree, and Zn, Cu, Pb, and As showed significant
enrichment. The main sources of the elements in PM10 and PM2.5 road dust fall in
Tianjin were soil dust, construction dust, traffic dust (motor vehicle exhaust,
tire wear, and brake wear), and coal combustion.
PMID- 29965442
TI - [Particle Size Distribution and Human Health Risk Assessment of Heavy Metals in
Atmospheric Particles from Beijing and Xinxiang During Summer].
AB - Under a condition of good air quality (AQI:55-90, PM10:37-97 MUg.m-3, PM2.5:17-76
MUg.m-3), six groups of 54 samples were collected using an Andersen cascade
impactor from both the indoor and outdoor stations in Beijing and Xinxiang from
June to August in 2016. The samples were digested by microwave digestion, and
nine heavy metal elements (Pb, Cr, Ni, Cu, Zn, As, Cd, Mn, and Co) in the
atmospheric particles were determined with an inductively coupled plasma source
mass spectrometer (ICP-MS). The results showed that the enrichment index (0-3) of
most elements were low in both cities except for Cd[15.0 (Beijing) and 8.47
(Xinxiang)]. Cr, Co, Cu, and Mn in the atmospheric particles from Beijing park,
Cd, Pb, and Mn in the atmospheric particles from the Beijing office, Cr, Co, Ni,
and As in the atmospheric particles from Xinxiang park, and all nine heavy metal
elements in the atmospheric particles from roads in both cities were found to be
more concentrated in the coarse fractions; however, Pb, Zn, Cd, Ni, and As in the
atmospheric particles from Beijing park, Co, Zn, Ni, Cr, As, and Cu in the
atmospheric particles from the Beijing office, Pb, Zn, Cd, Cu, and Mn in the
atmospheric particles from Xinxiang park, and all nine metal elements in the
atmospheric particles from the Beijing office showed the opposite pattern. The
result of a human health risk assessment indicated that the carcinogenic risk of
the five carcinogenic elements were all less than 10-4, but a lower potential
cancer risk would also occur under long term exposure. For the four non
carcinogenic elements (Pb, Zn, Mn, and Cu), the non-carcinogenic health risk
values of Pb, Zn, Mn, and Cu in the atmospheric particulates in Beijing were all
far less than 1, which means the corresponding non-carcinogenic risk was
negligible; and, except for Mn, there was no obvious non-carcinogenic risk from
Pb, Zn, and Cu in the atmospheric particles of Xinxiang.
PMID- 29965443
TI - [Ecological and Health Risks of Trace Heavy Metals in Atmospheric PM2.5 Collected
in Wuxiang Town, Shanxi Province].
AB - The pollution of atmospheric PM2.5 and ambient air quality were investigated in
Wuxiang Town, Shanxi Province, China, and the ecological and health risks of the
trace heavy metals in PM2.5 were analyzed. The PM2.5 samples were collected every
day using a medium-volume PM2.5 sampler in autumn (from Oct. 22 to Nov. 19, 2014)
and in winter (from Jan. 12 to Feb. 13, 2015) on the roof of a building at the
Wuxiang Environmental Protection Agency (EPA). The mass concentrations of PM2.5
were determined gravimetrically, and the contents of seven trace heavy metals (i.
e., As, Cd, Cr, Cu, Ni, Pb, and Zn) in PM2.5 were obtained using Inductively
Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The pollution extent,
sources, and potential ecological and health risks of the trace heavy metals in
PM2.5 were identified and assessed using the geo-accumulation index, ecological
risk index, a correlation and principle component analysis, and the exposure risk
models of US EPA. Results showed that the average concentration of PM2.5 in
winter, approximately three times higher than that in autumn, exceeded the
national secondary standard of ambient air quality (GB 3095-2012) on 65% of the
sampling days. The heavy metals in PM2.5 mainly originated from anthropogenic
activities, with contributions of 58.38% and 18.73% from coal combustion and
vehicular emission, respectively. In general, the levels of the heavy metals in
PM2.5 followed the order of Cu > Zn > Pb > Cr > As > Ni > Cd, with higher
ecological risks from Cd and Cu and higher non-carcinogenic and carcinogenic
risks from Cr compared with other metals. It is suggested that greater coal
combustion in winter under the adverse geographical conditions for air diffusion
in Wuxiang Town were responsible for the increased atmospheric PM2.5
concentration and their ecological and health risks in heavy metals.
PMID- 29965444
TI - [Characteristics of Particulate and Inorganic Elements of Motor Vehicles Based on
a Tunnel Environment].
AB - Respirable particulate matter(PM2.5)samples were collected at different locations
(inside and outside the tunnel) at the Zhang Zizhong Tunnel in Tianjin in
September 2015. Seventeen inorganic elements were measured, and the sources were
analyzed by the PCA receptor model. The results show that the daily average
concentration of PM2.5 inside and outside the tunnel is (94.79+/-62.78) MUg.m-3
and (83.92+/-61.60) MUg.m-3, respectively. The concentration during the working
day is higher than on a non-working day, and, to a certain extent, PM2.5
concentration in the tunnel during peak periods is correlated with the vehicle
flow, which indicates that PM2.5 concentration is affected by motor vehicle
pollution seriously. In the tunnel, the concentrations of Si, Fe, Al, Ca, and Mg
are higher, the mass fraction reach 98.48% of all analyzed elements and these
elements are less affected by vehicles. Fe and trace heavy metals (Zn, Cu, and
Pb) are related closely to motor vehicle pollution. From the Wilcoxon Signed-Rank
test, there are significant differences in Ba, Cu, Zn, Mo, Sn, and Sb inside and
outside the tunnel. Enrichment factors inside and outside the tunnel show that
the enrichment factor ratios of Co, Mn, Cr, Ca, Mg, Ba, Fe, Mo, and V are less
than 5, which are mainly from the crust. In addition, the enrichment factor
ratios of Cu, Zn, Pb, Sn, Sb, and Cd are greater than 5, which are affected
largely by anthropogenic sources. The factor analysis indicates that the main
pollution sources in the tunnel are the mixed sources of wear and the combustion
of fuel, the dust, and the combustion of diesel vehicles. In addition, in order
to analyze the source of motor vehicle pollution further, a factor analysis
indicates that the main pollution sources are tire wear and exhaust emission,
brake wear and exhaust emissions, and diesel emissions.
PMID- 29965445
TI - [A 2013-based Atmospheric Ammonia Emission Inventory and Its Characteristic of
Spatial Distribution in Henan Province].
AB - Based on the best available activity data at a city level from top down and
bottom up methods, a 2013-based emission inventory of NH3 was established for the
Henan Province using an emission factors method. The 3 km*3 km spatial gridded
distribution was carried out by using GIS technology. The results showed that the
total amount of atmospheric NH3 emission in Henan Province in 2013 was 1035.3 kt,
and the average emission intensity reached levels of 6.4 t/km2. Livestock and
nitrogen fertilizer applications were the top two emission sources, accounting
for 52.71% and 31.53% of the total emissions, respectively. Beef, laying hen, and
goats were the main contributors in the livestock category, accounting for
34.98%, 16.63%, and 14.02% of the total emissions, respectively. There were
different characteristics between emission source contributions and emission
intensities in each city. Nanyang, Zhoukou, Shangqiu, and Zhumadian were the
prefecture-level cities with large emissions, accounting for 11.53%, 9.84%,
9.62%, and 9.57% of the total amount in Henan Province, respectively. The NH3
emission intensities of Puyang and Louhe were larger than those of other cities,
reaching up to 10.7 t.km-2 and 10.2 t.km-2, respectively. The spatial
distribution revealed that emissions in the middle eastern region were relatively
higher; whereas, the western region emissions were relatively low. The areas with
high emissions were concentrated in the plains and densely populated areas.
PMID- 29965446
TI - [Emission Characteristics of Wind Erosion Dust from Topsoil of Urban Roadside
Tree Pool].
AB - This study characterized the wind erosion dust emissions from topsoil of urban
roadside-tree pool. The study area is the Xicheng District of Beijing and uses
GIS to obtain the spatial distribution of various road mileages. A full bore
investigation method was carried out to survey tree pool in the Zhanlanlu
Subdistrict to obtain the activity level of tree pool in the Xicheng district.
The portable in situ wind erosion laboratory (PI-SWERL) was used to determine the
emission factors of PM2.5 from the wind erosion dust from tree pool and to
estimate the PM2.5 emission inventory of tree pool in the Xicheng District in
2016. The results showed that:1The annual emission factors per unit area of PM2.5
from tree pool of freeways' frontage roads, major roads, minor roads, and alleys
are 47.9, 7.9, 14.9, and 29.9 g.(m2.a)-1, respectively. The reduction rate of
PM2.5 emission factors from tree pool by precipitation was about 30.3% in 2016.
2The annual emission factors per unit mileage of PM2.5 from the tree pool of
freeways' frontage roads, major roads, minor roads, branch roads, and alleys are
2.57, 2.33, 4.04, 7.31, and 5.44 kg.(km.a)-1, respectively, and the factors for
branch roads are 1.3, 1.8, 2.8, and 3.1 times as much as those for alleys, minor
roads, freeways' frontage roads, and major roads, respectively. Taking the
emission factor for minor roads as an example, the winter emission factor is 1.3,
7.3, and 8.7 times greater than that in the spring, summer, and autumn,
respectively. 3PM2.5 emissions from the tree pool in the Xicheng District of
Beijing are 1.60 t.a-1, and the uncertainty range of the emission inventory is
143%~184%. The emissions in winter are 0.68 t.a-1, which are 1.1, 1.42, and 5.1
times greater than that in the spring, summer, and fall, respectively. The
emission values for freeways' frontage roads, major roads, minor roads,
collectors, and alleys account for 5.6%, 8.7%, 23.2%, 4.1%, and 58.4% of the
total emissions, respectively. It is recommended that the urban roadside-tree
pool be covered to reduce wind erosion dust emissions with materials that do not
affect the growth of trees as soon as possible.
PMID- 29965447
TI - [Particulate Component Emission Characteristic from a Diesel Bus with DOC and
CDPF].
AB - A diesel bus was tested with a China City Bus Cycle (CCBC) on a heavy chassis
dynamometer, and the components of the particulate emissions with different after
treatment equipment were investigated. Results showed that OC was less than EC in
the particulates of the bus emissions without the use of after-treatment
equipment. The organic components were mainly fatty acids (60.9%) and n-alkanes
(32.4%), with a few hopanes and PAHs. Fatty acid components were mainly C16:0,
C18, C14, and C18:1. The n-alkanes were mainly C18-C24, with C21H44 and C22H46
accounting for the greatest portion. PAH mass was concentrated in medium and
small molecular weight components, such as Pyr, FL, and PA. While PAH toxicity
was dominated by medium and high molecular weight components, BaP was the most
toxic, followed by B(b+k)F, BaA, and IcdP. The total toxicity of the PAHs
decreased by 2.7% after DOC treatment and continued to decrease by 89.6%-93.8%
after CDPF treatment. After-treatment equipment significantly reduced the OC+EC
emissions by 18.9% (DOC) and 70.5%-72.5% (CDPF), but the reduction rate varied
from one component to another. The different precious metal loadings of the CDPF
did not obviously affect the reduction rate.
PMID- 29965448
TI - [Water Quality in the Henan Intake Area of the South-to-North Water Diversion
Project].
AB - The molecular weights, as well as the hydrophobicity composition of natural
organic matter (NOM) in raw water, were investigated in the Henan intake area of
the South-to-North Water Diversion Project. This study also discusses the
formation of carbonaceous disinfection by-products and nitrogenous disinfection
by-products during chlorination and chloramination of raw water in this area.
Most of the NOM in raw water were small molecules and hydrophobic fractions. The
molecular weight fractions of <1*103 were the most abundant, accounting for 57%
of the NOM. The hydrophobic fractions were the most abundant and accounted for
50% of the NOM. Two kinds of C-DBPs (CF and DCBM) and two kinds of N-DBPs (DCAN
and TCNM) were mainly produced after chlorination and chloramination, and the
formation potential of CF was about 120 MUg.L-1 after chlorination. Results of
chloramination showed that the productions of CF and DCBM by this process were
about 90% and 84.9% lower than that by chlorination. However, the amount of N
DBPs increased, and among them the amount of DCAN increased by about 2.3 times,
but the overall N-DBPs formation potential was still low and less than 6 MUg.L-1.
The results of this study can provide theoretical and technical support for the
process selection and optimization of the waterworks in the Henan intake area of
the South-to-North Water Diversion Project.
PMID- 29965449
TI - [Spatio-Temporal Patterns and Environmental Risk of Endocrine Disrupting
Chemicals in the Liuxi River].
AB - This study aimed to investigate the occurrence and spatio-temporal distribution
of 4-tert-octylphenol (4-t-OP), 4-nonylphenol (4-NP), triclosan (TCS), estrone
(E1), 17beta-estradiol (E2), and bisphenol-A (BPA) as endocrine disrupting
chemicals (EDCs) in the water of the Liuxi River and to evaluate the risks for
estrogenic activity. The results showed that EDCs had been detected at the 14
monitoring sites and the total concentration ranged from 26.07 ng.L-1 to 7109.5
ng.L-1, with the highest contribution rate coming from 4-NP (78.62%), followed by
BPA (11.91%), and the other four EDCs (<= 4.92%). On a spatial and temporal
scale, the EDC contents increased longitudinally from upstream to downstream,
especially in the heavily-polluted Baiyun section where the water quality was
lower than level V. The EDC contents in the tributaries were much higher than
those in the main channels. Influenced by the monsoon precipitation, the contents
of 4-NP, 4-t-OP, and total EDCs in the rainy season were significantly (P<0.05)
higher than those in the dry season, while the seasonal changes of E1 and E2
followed the opposite tendency. A Pearson correlation analysis showed that DO was
significantly negatively correlated with all the EDCs, suggesting that the EDCs
and reductive organic pollutants might coexist. As TN, TP, NH4+-N, permanganate
index, and EC were significantly positively correlated with E1, E2, BPA, and TCS
but not obviously correlated with 4-NP (P>0.05), we presumed that the pollution
source of E1, E2, BPA, and TCS might be the same with nitrogen and phosphorus
nutrition, originating from the point source emission of the domestic sewage,
industrial, and agricultural wastewater. In contrast, 4-NP and 4-t-OP more likely
originated from the non-point source pollution from agriculture. RDA results
showed that the variation of the EDCs contents by season was more obvious than
that in space (RDA1 56.14%>RDA2 14.20%), which was much more influenced by 4-NP
in the rainy season and by BPA in the dry season. As E1, E2, and TCS were
positively correlated with the Cu, Zn, cyanide, and fecal coliform, these three
target compounds could be used to indicate the multiple pollution components for
water quality. Compared with the worldwide reported EDC contents in waters, 4-NP,
BPA, and TCS contents in the middle and lower reaches of the Liuxi River were at
higher levels, while E1, E2, and 4-t-OP were at the middle and lower levels. The
risk assessment for estrogenic activity showed that the RQ values in the middle
and lower reaches of the Liuxi River were all greater than 1, indicating that the
downstream river sections were under high risk for estrogenic activity. As a
result, appropriate precautions are needed to improve environmental management.
PMID- 29965450
TI - [Fate and Origin of Major Ions in River Water in the Lhasa River Basin, Tibet].
AB - In order to understand the temporal and spatial variations of major ions in water
and their sources in the Lhasa River Basin, water samples were collected monthly
at the hydrological station in the Lhasa River from August 2014 to July. The
results show that HCO3- is the dominant anion in the water of the Lhasa River,
which accounts for 68.73% of the anions, followed by SO42-. Ca2+ is the dominant
cation, which accounts for 67.75% of the cations, followed by Mg2+. The pH values
of the river water range between 8.31 and 8.90, with a mean of 8.59 throughout
the year, generally showing alkaline water. The highest pH values occur in
summer, which is probably due to the photosynthesis of aquatic plants and the
growth of phytoplankton. Electrical conductivity (EC) varies between 155.0 and
257.0 MUS.cm-1, with a mean of 210.5 MUS.cm-1. Because of the frequent uplift of
the Tibetan Plateau that enhanced the mechanical weathering of rocks and mineral
dissolution, the total dissolved solid (TDS) concentration, at an average of
181.35 mg.L-1, is significantly higher than the average value of rivers around
the world. The Lhasa River is recharged by surface runoff, so the concentrations
of major ions in water are higher during winter, but lower in summer. An ion
source analysis indicates that Ca2+, Mg2+, and HCO3- are mainly derived from
chemical weathering of carbonate minerals, Cl-, SO42-, and NO3- are mainly
affected by precipitation and rock weathering. Furthermore, the concentrations of
major ions in the water have a negative correlation with the river discharge
rate, which suggests there might be a dilution effect occurring during the rainy
season.
PMID- 29965451
TI - [Identification of Nitrate Sources and the Fate of Nitrate in Downstream Areas: A
Case Study in the Taizi River Basin].
AB - A total of 14 samples were collected in May 2016(dry season)and August 2016 (wet
season) in the downstream area of the Taizi River. ?15 N-NO3- and ?18 O-NO3- were
determined using the azide method, and ?18 O-H2O was determined using a CO2-H2O
equilibration technique. To identify NO3- sources and transformations in the
downstream area of Taizi River Basin, ion chromatography, Nessler's reagent
spectrophotometry, the azide method, and CO2-H2O equilibration methods were
utilized to determine the concentrations of NO3-, Cl-, NH4+-N, and isotopic
compositions (?15 N and ?18 O) of NO3- and the ?18 O-H2O in surface water. The
results showed that the NO3- was mainly derived from mixed sources. During the
dry season, the nitrate in the surface water was derived from soil nitrogen,
manure, and sewage in the upper reaches, and mainly derived from synthetic
fertilizer, manure, and sewage in the middle and lower reaches of the Beisha
River. The nitrate was mainly derived from manure and sewage in the Nansha River.
The nitrate was mainly derived from soil nitrogen in the upper reaches, mainly
derived from synthetic fertilizer, manure, and sewage in the middle reaches, and
mainly derived from manure and sewage in the lower reaches of the Haicheng River.
During the wet season, the nitrate sources in surface water were soil nitrogen,
synthetic fertilizer, manure, and sewage in the Beisha River; synthetic
fertilizer, manure, and sewage in the middle and lower reaches of the Haicheng
River and the Nansha River; and soil nitrogen and synthetic fertilizer in the
upper reaches of the Haicheng River. NO3- and NH4+-N concentrations decreased
with increasing ?15 N-NO3- from the dry season to the wet season, indicating that
volatilization of NH4+-N and denitrification of NO3- might occur during the wet
season. There is a slightly positive relationship between the reciprocal of the
concentration of 1/rho(NO3-) and ?15 N-NO3- during the wet season, indicating
that mixing processes occurred in surface water. The results will provide
information on nitrate sources during seasonal variations in the plain areas.
PMID- 29965452
TI - [Sources, Distribution of Main Controlling Factors, and Potential Ecological Risk
Assessment for Heavy Metals in the Surface Sediment of Hainan Island North Bay,
South China].
AB - The distribution characteristics of the content of As, Cr, Cu, Hg, Pb, Zn, and Cd
were researched based on the geochemical analysis of 159 surface sediment samples
in Haikou Bay, Puqian Bay, Dongzhai Harbor, and Mulan Bay Mathematical statistics
methods were used to interpret the sources of heavy metals, and the main
controlling factors for heavy metal distribution were confirmed, having been
analyzed qualitatively and semi-quantitatively. The results showed that the
average contents of As, Cd, Cr, Cu, Hg, Pb, and Zn were 8.40, 0.06, 32.50, 8.32,
0.02, 18.77, and 35.87 MUg.g-1, respectively. High contents of Cr, Cu, Hg, Pb,
and Zn are mainly distributed in estuaries and harbors. The content of As
increased gradually from south to north in the research area, while Cd gathered
mainly in Haikou Bay. The source of Cu, Zn, Hg, Pb, Cr, and Cd in sediment was
terrestrial input, which was controlled by anthropogenic pollution and migration
of weathered products from mother rock. The source of As could be overseas
material input. The grain size of sediment was the main factor controlling the
contents of Cu, Zn, Hg, Pb, and Cr, and it was found that sediments with a finer
grain size have more heavy metals adsorbed. The high As content was controlled
mainly by the natural geological background factor, while the content of Cd
reflected the difference in regional pollution caused by differing development in
cities. Three surface sediment samples were evaluated as class II of the National
Marine Sediment Standard due to the content of As, while six surface sediment
samples were evaluated as class II due to the content of Cr, of which the
pollution degree was moderate. The concentrations of Cd, Cu, Hg, Pb, and Zn in
all of the 159 sediment samples fall in the I class, of which the pollution
degree is low. The degree of pollution for seven heavy metals were arranged in
the following order:As > Cr > Pb > Zn > Cu > Cd > Hg. The potential ecological
risk assessment results indicated that all heavy metals in surface sediment
caused low levels of pollution generally, and that each heavy metal element was
at a low ecological risk level. The order for the ecological risk of the seven
heavy metals was:As > Hg > Cd > Pb > Cu > Cr > Zn; therefore, As was the main
ecological risk factor. In general, the potential ecological risk for heavy
metals was low, which illustrated that the marine environment in the study area
was excellent.
PMID- 29965453
TI - [Characteristics of Heavy Metals Pollution of Farmland and the Leaching Effect of
Rainfall in Tianjin].
AB - The leaching effect of the rainfall process for removing heavy metals from
farmland soils is a critical physical process. To study the leaching effect of
the rainfall process on heavy metals in soil, the pollution characteristics of
seven heavy metals in farmland soil have been investigated in the suburban
Tianjin region by combining the current data with previously reported runoff data
in the same region. There is a large difference for these tested heavy metals in
soils, with Zn having the highest concentration at 106.61+/-56.24 mg.kg-1 and Cd
having the lowest concentration at 0.31+/-0.31 mg.kg-1. Compared with the
background value in Tianjin, only the content of Cd is at higher levels (a four
fold increase). The results from a single factor pollution index and
comprehensive pollution index analysis indicate that the comprehensive pollution
index ranking is Cd > Cu > Ni > Zn > As ~ Cr > Pb. Cd, Cu, Ni, and Zn are in the
moderate pollution, mild pollution, and alert level categories, respectively.
Except for As, the results from a correlation analysis, the principal component
analysis (PCA), and the cluster analysis indicate the possible similar origins of
Cr, Ni, Cu, Zn, Cd, and Pb. The multivariate statistical analysis indicates that
Cd is mainly derived from human activities, Zn, Cu, Cr, Ni, and Pb are affected
by anthropogenic and natural sources, and As is mainly influenced by natural
conditions. By comparing the ratios of individual heavy metals to Cr in soils and
runoffs, the leaching behaviors have been studied, with the leaching capacity
ranked as Cd > As > Cu ~ Pb > Ni > Cr ~ Zn. In summary, Cd pollution in soil is
more prominent than pollution from other metals and should receive attention.
PMID- 29965454
TI - [Seasonal Difference in Water Quality Between Lake and Inflow/Outflow Rivers of
Lake Taihu, China].
AB - The seasonal and spatial variation of external nutrient loading from rivers and
their impact on lake water quality were analyzed in Lake Taihu, China, using the
monthly monitoring data from 16 major inflow/outflow rivers and 32 observation
sites in the lake. The results showed:1 The average monthly values of total
nitrogen (TN), dissolved total nitrogen (DTN), total phosphorus (TP), and
dissolved total phosphorus (DTP) in rivers were all higher than the corresponding
areas in the lake. Significant positive correlations were found between nutrient
concentrations in the inflow rivers and the corresponding areas in the lake,
indicating the pronounced impact of external loading on lake water. 2 Remarkable
seasonal variations of nutrient concentration were found both in the rivers and
in the lake. The highest TN and TP concentrations in inflow rivers were 4.82 mg.L
1 (March) and 0.218 mg.L-1 (December), while the highest TN and TP concentrations
in the lake were 4.13 mg.L-1 and 0.255 mg.L-1 in July. 3 Extreme rainfall events
could decrease the nutrient concentration in the rivers in the short-term, but
finally would increase the external loading of nutrients, and indicated
disadvantages for the restoration of Lake Taihu. Our study concluded that inflow
pollution showed an obvious "shaping effect" on the seasonal and spatial
distribution of water quality indicators in large and shallow lakes.
Additionally, the self-purification ability of lakes, wind-induced accumulation
and migration of algae, as well as the sediment resuspension under the prevailing
winds in different seasons, all have vital effects on nutrient concentrations and
their spatial-temporal variations.
PMID- 29965455
TI - [Characteristics of Nitrogen Release at the Sediment-Water Interface in the
Typical Tributaries of the Three Gorges Reservoir During the Sensitive Period in
Spring].
AB - Overlying water and sediment interstitial water samples were acquired to study
the nitrogen release between sediments and water interfaces in Xiangxi Bay in
April 2016 during the Sensitive Period in spring. The spatial distribution of
different forms of nitrogen in the sediment was analyzed, the diffusion fluxes of
different forms of nitrogen in the sediments and water systems were also
measured, and a correlation analysis with environmental factors was conducted.
The results show that overlying water and sediment interstitial water rho(TN)
ranges from 1.10 to 6.90 mg.L-1 and 6.19 to 32.57 mg.L-1 respectively; indicating
the nitrogen concentrations in the overlying and interstitial water of sediments
have a certain variation along the process and vertically. The interstitial water
nitrogen concentrations in the upstream area are higher than those in the
downstream area. The interstitial water rho(NH4+-N) in the sediment is
significantly larger than that in the overlying water, but the interstitial water
rho(NO3--N) in the sediment is slightly smaller than that in the overlying water.
Xiangxi Bay sediment acts as a source of NH4+-N; however, for NO3--N it is a
sink. The diffusive fluxes of NH4+-N range from 2.70 to 4.72 mg.(m2.d)-1; and the
diffusive fluxes of NO3--N range from -1.61 to -0.62 mg.(m2.d)-1. Nitrogen is
mainly present in the form of ammonium nitrogen in the sediment of Xiangxi Bay.
The rho(NH4+-N) in the sediment ranges from 69.97-1185.97 mg.kg-1, rho(NO3--N)
ranges from 2.78-38.17 mg.kg-1, and the rho(NH4+-N) in sediments in the surface
at 0-8 cm changes with the same trend.
PMID- 29965456
TI - [Spatial Distributions of Transferable Nitrogen Forms and Influencing Factors in
Sediments from Inflow Rivers in Different Lake Basins].
AB - It is necessary to investigate the distribution of nitrogen forms in river
sediments to recognize the water environment quality. In this study, ion
exchangeable form nitrogen(IEF-N), weak acid extractable form nitrogen (WAEF-N),
strong alkali extractable form nitrogen (SAEF-N) and strong oxidation extractable
form nitrogen (SOEF-N) in sediments were obtained by means of sequential
extraction procedures.We analyzed the spatial variations of nitrogen forms in
sediments from Taihu watershed (Dongtiaoxi River and Xitiaoxi River) and Hongzehu
watershed (Anhe River and Suihe River), and expounded the influence factors of
nitrogen form distribution. The results showed that the physicochemical
properties of sediments from different watersheds varied in space. The
concentrations of total nitrogen and nitrogen fractions also showed obvious
changes in river sediments. As a whole, the concentrations of total nitrogen and
transferable nitrogen in Taihu rivers were higher than those in Hongzehu rivers,
but the former showed smaller spatial changes. Sediments from Taihu rivers showed
the different concentration order of total nitrogen and transferable nitrogen
comparing with those from Hongzehu rivers. The former followed the order of SOEF
N > SAEF-N > IEF-N > WAEF-N, and the latter followed the order of SOEF-N > SAEF-N
> WAEF-N > IEF-N.The spatial varitions of transferable nitrogen fractions in
Hongzehu rivers were prominent, which was associated with nitrogen sources. The
spatial distributions of transferable nitrogen in sediments were obviously
affected by their physicochemical properties, especially for organic matter and
grain size.
PMID- 29965457
TI - [Effects of Hydrological and Meteorological Conditions on Diatom Proliferation in
Reservoirs].
AB - The proliferation of diatoms is an ecological disaster that harms the water
quality of many reservoirs in China. In order to reveal the driving factors of
abnormal algal blooms in reservoirs, phytoplankton community structure and the
associated environmental factors from 2009 to 2016 from Shahe Reservoir in
Tianmuhu were analyzed. Results showed that diatoms and there dominant genus were
predominately driven by temperature, and the relationship between hydrology and
nutrition was insignificant. Distinct relationships were recorded between
different diatom genera and temperature over the past eight years. The optimum
growth temperature of diatoms and Synedra were both 27C, while that for
Cyclotella and Achnanthes were both 19C. Low temperature was suitable for the
growth of Melosira, and its growth was compromised with increasing temperature.
In a multivariable statistical analysis of the dominant diatom genus and the
associated environmental factors, we found that the dominant diatom genus
responded differently to the associated environmental factors. The total biomass
of the diatom and the biomass of Synedra and Achnanthes were significantly and
positively correlated with rainfall (P<0.05). The biomass of Cyclotella was
significantly and positively correlated with total phosphorus, rainfall, and
water level (P<0.05) and significantly and negatively correlated with water
exchange rate (P<0.05). The biomass of Melosira was significantly and positively
correlated with total phosphorus. The annual peak biomass of diatoms can be
predicted by a multiple regression model with independent variables, including
rainfall intensity, dissolved total phosphorus, and the accumulated temperature
in winter and spring. Our results indicated that the proliferation of diatoms
responds significantly to hydrological and meteorological factors while
insignificantly to nitrogen and phosphorus loading. External load reduction is
needed to maintain a good water quality in the reservoir. In addition, extreme
weather conditions should be given attention to provide an early warning for
diatom proliferation.
PMID- 29965458
TI - [Vertical Distribution of Fungal Community Composition and Water Quality During
the Deep Reservoir Thermal Stratification].
AB - Freshwater fungal community composition plays pivotal roles in sustaining the
function and health of drinking water reservoir ecosystems. To investigate the
vertical evaluative characteristics of an aquatic fungal community under
conditions of stable thermal stratification, water samples were collected at 0.5,
10, 25, 40, 60 and 70 m depths of Jinpen Reservoir during thermal stratification.
Fungal community composition was determined using a high-throughput DNA
sequencing technique and combined with water quality parameters. The results
showed that the epilimnion, metalimnion, and hypolimnion water layers were formed
in Jinpen Reservoir. The temperature decreased steadily from the surface at
22.33C to the bottom with 7.21C (P<0.05). The dissolved oxygen (DO) concentration
decreased significantly from the surface to the bottom (P<0.05). The conductivity
and the concentration total phosphorus and iron increased significantly from the
surface to the bottom (P<0.05). The high-throughput DNA sequencing revealed a
total of 1247 operational taxonomic units (OTUs), which were affiliated with four
phylum, 14 classes, and 39 genera, including Zygomycota, Basidiomycota,
Ascomycota, and Chytridiomycota. The highest Shannon diversity and Chao 1 were
3.45 and 360 at 60 m, respectively. The Shannon diversity and Chao 1 were
significantly higher in the hypolimnion than in the metalimnion (P<0.05).
Rhodotorula (27.23%), Alternaria (24.28%),Cladosporium (22.98%), Alternaria
(32.00%), Didymella (17.47%), and Cladosporium (28.17%) were the dominant species
at 0.5 m, 10 m, 25 m, 40 m, 60 m, and 70 m, respectively. There are a number of
unclassified fungi at different water depths. The heat map profile indicated
significant differences in the vertical distribution of the fungal community
composition in Jinpen Reservoir. A principle component analysis (PCA) indicated
that water temperature, DO, TP, and conductivity had dramatic influences on the
vertical distribution of the fungal community composition. The results provide
new insights on the relationship between water quality and fungal community
composition during reservoir thermal stratified periods.
PMID- 29965459
TI - [Community Structure and Influencing Factors of Bacterioplankton in Spring in
Zhushan Bay, Lake Taihu].
AB - In order to investigate the characteristics of bacterioplankton in the spring in
Zhushan Bay, Lake Taihu, the 16S rRNA gene of the bacterioplankton at four
sampling sites in Zhushan Bay was sequenced by high-throughput sequencing using
water samples collected from Yapugang, Shatanggang, Zhushanhunan, and Jiaoshan.
The results showed that the coverage of the sequencing library was very high and
could accurately represent the bacterioplankton community in the samples. The
species richness of Jiaoshan was the highest, but the species evenness was lower.
Cyanobacteria, Actinobacteria, Proteobacteria, and Bacteroidetes were the
dominant phylum in Zhushan Bay. The average abundance of Cyanobacteria was as
high as 64.73%, which indicated an outbreak of cyanobacteria bloom in the water.
At the genus level, Anabaena, hgcI_clade, CL 500-29 _marine_group, Microcystis,
Synechococcus, and Mycobacterium were predominant. The results of redundancy
analysis (RDA) for the relationship between bacterioplankton and environmental
factors showed that water temperature, chlorophyll a (Chl-a), ammonia
nitrogen(NH4+-N), dissolved oxygen (DO), and phosphate (PO43--P)were the main
environmental factors affecting the bacterioplankton community. Dissolved oxygen
could significantly affect Microcystis; nutrient and water temperature also had
an effect.
PMID- 29965460
TI - [Characteristics of Sediment Oxygen Demand in a Drinking Water Reservoir].
AB - Depletion of dissolved oxygen (DO) in the hypolimnetic layer during
stratification periods and its deleterious effects on water quality have been
widely observed. However, it is still difficult to comprehend conceptually the
processes of oxygen consumption at the sediment-water interface. The research
presented here is, therefore, based on an areal hypolimnetic oxygen demand (AHOD)
model to address three key themes related to the sediment oxygen demand (SOD):1
the characteristics of sediment and its influences on SOD; 2 evaluation of SOD
with different turbulence levels overlying the sediment; and 3 the influence of
microbial metabolic activity on SOD. Sediment samples were collected at the
entrance to and over the basin area of Jinpen Reservoir, and a sediment-water
experimental chamber was designed to achieve these goals. The results showed
that, under quiescent conditions, the SOD5area(SOD at DO of 5 mg.L-1) were 0.13
g.(m2.d)-1 and 0.36 g.(m2.d)-1 in the arm and basin, respectively. Under dynamic
conditions, the slight mixing of the water column near the sediment induced an
increase in SOD and resulted in a gradual shift from first-order to zero-order DO
uptake. The organic matter content in the reservoir arm and profundal sediment
were 44.43 mg.g-1 and 45.12 mg.g-1, respectively. The microbial metabolic
activity in the basin was stronger, and the total fluorescence intensity of the
dissolved organic matter (DOM) in the profundal sediments was about 1.5 times
that in the reservoir arm. These results suggest that SOD will be higher when
microbial metabolic activity is stronger and organic matter content is higher in
sediments. The oxygenation aeration techniques should be designed to meet the
oxygen demand of the deep reservoir to provide a theoretical basis for improving
the oxygenation efficiency.
PMID- 29965461
TI - [Effects of Wastewater Nitrogen Concentrations and NH4+/NO3- on Nitrogen Removal
Ability and the Nitrogen Component of Myriophyllum aquaticum (Vell.) Verdc].
AB - Solution culture experiments were conducted to investigate the effect of
wastewater nitrogen levels and NH4+/NO3- on nitrogen removal ability and the
nitrogen component of Myriophyllum aquaticum. Experiments with three nitrogen
levels and NH4+/NO3- were set up as follows:20, 100, and 200 mg.L-1and NH4+/NO3-
1:0, 0.5:0.5, and 0:1. The results showed that the biomass of plants increased
fastest during the first week. The plants treated with NH4+/NO3-=1:0 with
nitrogen levels of 20 and 100 mg.L-1 and those treated with NH4+/NO3-=0.5:0.5
with a nitrogen concentration of 200 mg.L-1 exhibited higher biomass than the
others. The removal rates of water total nitrogen, ammonium nitrogen, and nitrate
nitrogen during the first week were the maximum for all treatments and increased
with water nitrogen levels. There were no significant differences in the removal
rate between ammonium nitrogen and nitrate nitrogen with a nitrogen level of 20
mg/L, while with nitrogen levels of 100 and 200 mg.L-1, the nitrate removal rates
were higher than those for ammonium nitrogen. The Myriophyllum aquaticum nitrogen
accumulation and its contribution rate to nitrogen removal from water and
sediment were all increased with water nitrogen levels and increased fastest
during the first week. The contribution rate of nitrogen accumulated by plants
with NH4+/NO3-=0:1 was the highest with nitrogen levels of 20 mg.L-1, while
plants with NH4+/NO3-=0.5:0.5 were the highest with nitrogen levels of 100 and
200 mg.L-1. The protein, amino, and nitrate nitrogen contents in Myriophyllum
aquaticum plants were all increased by increasing water nitrogen levels with a
ranking of protein content > amino nitrogen content > nitrate nitrogen content.
The protein concentrations in plants with NH4+/NO3-=1:0 and NH4+/NO3-=0.5:0.5
were higher regardless of water nitrogen levels, while the amino nitrogen
concentration in plants with NH4+/NO3-=1:0 and the nitrate nitrogen content in
plants with NH4+/NO3-=0:1 were higher than the others. It was concluded that the
nitrogen removal ability of Myriophyllum aquaticum was improved by raising water
nitrogen levels under the tested condition, which indicates that Myriophyllum
aquaticum could purify high nitrogen wastewater. Myriophyllum aquaticum is an
ammonium-nitrophile, but had the strongest capacity for growing and removing
wastewater nitrogen exhibited with higher than 100 mg.L-1 nitrogen levels only
with equal NH4+ to NO3-. The nitrogen component concentrations of protein, amino,
and nitrate in Myriophyllum aquaticum plant were all affected by the ratio of
NH4+/NO3-.
PMID- 29965462
TI - [Effect of Nutrient Loadings on the Regulation of Water Nitrogen and Phosphorus
by Vallisneria natans and Its Photosynthetic Fluorescence Characteristics].
AB - Submerged macrophytes are an important component of aquatic ecosystems. During
the growing period, submerged macrophytes can absorb nitrogen and phosphorus
nutrients to reduce pollution loadings. Shoots of submerged macrophytes can also
promote the adhesion of suspended substances in water, reducing the turbidity.
The release of nutrients in sediments can be suppressed by its root system, and
the resuspension of sediments caused by disturbance of winds and waves can also
be resisted. The role of submerged macrophytes in ecological restoration of
eutrophic lakes has attracted widespread attention. In 1960, the submerged plants
Vallisneria natans and Potamogeton malaianus had been the dominant species in
East Taihu. However after 2002, Nymphoides peltatum, Elodea nattalii, P.
malaianus, etc. have gradually taken over the dominant roles along with
significant elevations of nitrogen and phosphorus levels. Nutrients in water are
not the only key factors causing eutrophication of water bodies; the nutrient
source for submerged plant growth affect both the purification efficiency and the
photosynthetic characteristics of submerged macrophytes. Excessive nitrogen and
phosphorus concentrations can inhibit the photosynthetic physiological activities
of submerged macrophytes, affecting the succession of aquatic vegetation. In
addition, under high nutrient conditions, the competition from periphytic algae
and planktonic algae may also directly poison submerged macrophytes, leading to
its degradation and disappearance. Systematic studies on the regulation and
photosynthetic fluorescence response mechanism of submerged macrophytes to varied
nutrient loadings are helpful in revealing their relationships. The seedlings of
submerged macrophyte V. natans were transplanted in a laboratory mesocosm to
study the effect of nutrient loadings on its regulation of water nitrogen and
phosphorus. Three nitrogen and phosphorus loadings from low, medium, and high
levels derived from nitrate, ammonium, and phosphate were setup as the aquatic
medium for the plant growth. Twelve harvests were carried out to determine the
evolution of nutrient removal performance of V. natans. Its photosynthetic
fluorescence characteristics were measured by a pulse-amplitude modulated
fluorometer (Diving-PAM). Results showed that the nitrogen and phosphorus
adsorption abilities of V. natans were gradually enhanced with the increase of
nutrient concentrations in the range of TN <= 12 mg.L-1 and TP <= 1.0 mg.L-1. In
the treatment of high nutrient concentrations (TN=12 mg.L-1 and TP=1.0 mg.L-1),
the removal rates of nitrogen and phosphorus reached more than 95%. V. natans
preferentially absorbed ammonium nitrogen when its concentration was high. The
medium nutrient concentrations (TN:8-12 mg.L-1 and TP:0.6-1.0 mg.L-1) did not
significantly affect the Fv/Fm ratio of leaves. However, the low nutrient
concentrations (TN=3 mg.L-1 and TP=0.3 mg.L-1) could improve the Fv/Fm ratio of
leaves and were beneficial for the growth of V. natans. The inhibition of
photosynthetic activity and light tolerance were enhanced with the increase in
nutrient concentrations. The photosynthetic activity of V. natans gradually
recovered with no significant changes in the capacity for light harvesting, when
the nutrient concentrations gradually decreased in the water. Our results
indicate that the high nitrogen and phosphorus loadings indeed hamper the
photosynthetic capacity, which may subsequently restrain the maintenance of the
dominance of V. natans in the submerged macrophyte communities.
PMID- 29965463
TI - [Removal of Organic Matter from Water by Chemical Preoxidation Coupled with
Biogenic Manganese Oxidation].
AB - In the process of drinking water treatment, potassium permanganate and iron
manganese oxides are typical pre-oxidation methods that can not only effectively
remove organic matters in drinking water, but also reduce the production of
disinfection by-products (DBPs). However these two pre-oxidation methods will
produce Mn2+ that is genotoxic. In order to solve this problem, a concept was
proposed to connect biogenic-manganese oxidation technology after chemical
oxidation. The manganese-oxidizing microbe may convert Mn2+ into the bio
manganese oxide, which can further remove the pollutants by its strong oxidative
and adsorption capacity to improve water purification. In the simulated
contaminated water composed of natural organic tyrosine (Tyr) and synthetic
organic 2-Hydroxy-4-Methoxybenzophenone-5-Sulfonic Acid (BP-4), we verified the
proposed the concept. Pre-oxidation by potassium permanganate or iron-manganese
oxides efficiently removed Tyr, but had negligible effect on BP-4. During this,
Mn2+ was generated. In the subsequent biological system, the manganese-oxidizing
bacteria Pseudomonas sp. QJX-1 could utilize the Tyr for growth and oxidize Mn2+
to Mn4+ oxide. The generated manganese oxides could then effectively remove BP-4.
In comparison, the moderate potassium permanganate preoxidation coupled with bio
manganese oxidation had a desirable treatment effect, with 100%, 50%, and 98.9%
removals for Tyr, BP-4, and Mn2+, respectively. Importantly, the study provides a
new method for drinking water treatment.
PMID- 29965464
TI - [Treating Simulated Dye Wastewater by an In Situ Copper Ferrite Process].
AB - Four types of simulated dye wastewater containing methylene blue, tartrazine,
Congo red, and crystal violet were treated by an in situ copper ferrite process,
and the influencing factors of the operational parameters in this process were
studied. The main mechanism of dye removal was suggested by reaction
thermodynamics and solid products characterization for methylene blue removal.
The results showed that an in situ copper ferrite process could effectively
remove four kinds of simulated dyes by adjusting reaction conditions
appropriately. The maximum capacities of the in situ copper ferrite process for
methylene blue, crystal violet, tartrazine, and Congo red were 349.2, 382.2,
402.5 and 831.8 mg.g-1, respectively, under reaction condition of c(Cu2+) of 0.01
mol.L-1, c(Fe2+) of 0.025 mol.L-1, c(OH)/c(M)=1.7 (hydroxyl and metal molar
ratio), reaction temperature of 40C, and reaction time of 60 min. Comprehensive
physical interactions, including a sweeping effect, encapsulation, and high
active surface adsorption of the in situ Fe-Cu precipitates were the dominant
mechanisms in dye removal by the process. Copper ferrite, as an effective
magnetic adsorbent and a highly efficient environmental catalyst, was regenerated
by magnetic separation, catalytic oxidation, and high temperature calcination.
PMID- 29965465
TI - [Experiment to Enhance Catalytic Activity of alpha-FeOOH in Heterogeneous UV
Fenton System by Addition of Oxalate].
AB - alpha-FeOOH was prepared by a symmetrical precipitation method and characterized
by XRD, FT-IR, SEM, BET, and EDS techniques. The oxalate enhanced experiment for
the catalytic activity of alpha-FeOOH during the degradation of Orange II by the
heterogeneous UV-Fenton process was evaluated. The results showed that the rate
of Orange II degradation in this heterogeneous UV-Fenton system could increase
significantly with oxalate as an enhancing reagent, with the peak values of
enhanced efficiency reaching 116.9% when the concentration of additional oxalate
was 0.4 mmol.L-1. Under this condition, more than 99% of Orange II (0.2 mmol.L-1)
was degraded in 15 min. However, under the same condition, the inhibition ratios
of malonate, acetate, EDTA and citrate were 5.2%, 8.1%, 23.2%, and 25.7%,
respectively. Compared with the basic system, the enhanced efficiency of the
mineralization rate constant can reach 69.9% when the concentration of additional
oxalate was 0.4 mmol.L-1. As a result, the time required for mineralization could
be reduced greatly. In the heterogeneous UV-Fenton system, the additional oxalate
could provide a new photo-reduction pathway for Fe3+ to Fe2+, enhancing the ratio
of the homogeneous UV-Fenton process by increasing the Fe leaching of alpha-FeOOH
and the concentration of hydroxyl radicals, leading to higher degradation
efficiency of Orange II. As a result, an enhancement effect of 101.5% could be
obtained even after three cycles. The iron ions leached from catalysts could be
re-adsorbed after treatment, avoiding the loss of active species from catalysts
and additional pollution caused by iron ions. The results indicated that
additional oxalate was a stable and reliable enhancing reagent on the catalytic
activity of alpha-FeOOH in the heterogeneous UV-Fenton system.
PMID- 29965466
TI - [Fabrication of a Biomass-Based Hydrous Zirconium Oxide Nanocomposite for
Advanced Phosphate Removal].
AB - Wheat straws were modified by 3-chloro-2-hydroxypropyl trimethylammonium chloride
(CTA) to obtain aminated wheat straw St-N'. The optimum synthetic conditions were
determined to be NaOH with 30% mass fraction, CTA of 100 mL, reaction temperature
of 80C, and reaction time of 3 h, which was verified by orthogonal experiments.
Nano-sized hydrous zirconium oxides (HZO) were immobilized into St-N' by an in
situ precipitation method to obtain the nanocomposite St-N'-Zr. The SEM, TEM,
XRD, and BET results indicated that the nano-sized HZO with 50-100 nm sizes were
uniformly loaded onto the inner surface of the biomass-based carrier St-N' that
was amorphous in nature. A Langmuir adsorption isotherm fitted the adsorption
process well, and the maximum adsorption amount was calculated to be 33.90 mg.g
1. The optimal pH range was 1.8-6.0, displaying good removal capacity of
phosphate in acidic waters. In the presence of high levels of competing anions,
the phosphate adsorption still retained more than 70% of the original amount,
showing the higher preference of St-N'-Zr towards phosphate than towards the
commercial anion exchanger D-201. After 10 cycles of adsorption-desorption, the
removal efficiency remained stable, confirming the good regeneration ability and
potential application of St-N'-Zr.
PMID- 29965467
TI - [Characteristic of Nitrate Adsorption in Aqueous Solution by Iron and Manganese
Oxide/Biochar Composites].
AB - In this study, we synthesized Fe/Mn bimetallic oxide coated biochar sorbents by
pyrolysis of wheat straw impregnated with ferric chloride and potassium
permanganate and investigated their potential to adsorb nitrate in water. X-ray
photoelectron spectroscopy and scanning electron microscopy analysis suggests
that Fe(III)/Mn(IV) bimetallic oxide particles emerge on the sorbents. The
optimized sorbent could achieve a specific surface area of 153.116 m2.g-1 and a
point of zero charge of 9.76. Batch nitrate adsorption experiments were carried
out to investigate the influence of various factors, such as sorbent dosage,
initial solution pH, and co-existing anions. Results show that the sorbent
maintained a high adsorption capacity of 75.40%-78.70% over a wide range of pH
from 1.00 to 9.05, and the sorption mechanism was interpreted as ligand exchange.
The effects of co-existing anions on the nitrate sorption followed the decreasing
order of Cl- > SO42- > PO43-. Furthermore, the adsorption isotherms were well
described by the Langmuir model, and the sorbent could exhibit a quite
competitively high capacity of 37.3613 mg.g-1 for nitrate removal. In addition,
the accordance of sorption kinetics with the pseudo-second order model implied
that the sorption could be a multi-stage controlled chemical process. In
addition, the thermodynamic parameters suggested that the sorption reaction could
be a spontaneous and endothermic process. The results demonstrated that the Fe/Mn
bimetallic oxide coated biochar could serve as a promising agent for nitrate
removal from water.
PMID- 29965468
TI - [Preparation of PAAm/HACC Semi-Interpenetrate Network Hydrogel and Its Adsorption
Properties for Humic Acid from Aqueous Solution].
AB - New absorbents, polyacrylamide/chitosan quaternary ammonium salt semi
interpenetrate network hydrogels[(PAAm/HACC semi-IPN), (s-IPN 1.5), and (s-IPN
3)], were successfully prepared via in situ polymerization by thermal synthesis
for the removal of humic acid (HA) from aqueous solution. The materials were
characterized by SEM, FT-IR, and XRD. The adsorption behaviors of adsorbents for
HA were investigated as a function of pH, ionic strength, contact time, initial
HA concentration, and temperature. The results showed that s-IPN 3 outperformed s
IPN 1.5. The adsorption capacity of the adsorbent for HA decreased with an
increase in solution pH and decrease of temperature, and low ionic strength was
conducive to the adsorption of HA. The adsorption kinetics fitted to a pseudo
second-order kinetic model and the adsorption isotherms could be described by the
Sips isotherm model. The impressive maximum adsorption capacity could reach
238.08 mg.g-1 at the condition of pH=7.0, ionic strength=0.01 mol.L-1, and T=298
K. The adsorbent could remove HA from aqueous solution efficiently.
PMID- 29965469
TI - [Groundwater Arsenic and Silicate Adsorption on TiO2 and the Regeneration of
TiO2].
AB - Titanium dioxide (TiO2) was widely used to remove arsenic (As) from groundwater
due to its excellent properties. Previous studies show that the coexisting
silicate ions (Si) could occupy the available surface sites of TiO2 and further
inhibit As adsorption and TiO2 regeneration. To investigate the effect of Si
adsorption on the As molecular surface structure, an extended X-ray absorption
fine structure (EXAFS) analysis was conducted in this work. The results indicated
that the presence of Si exhibited no impact on the As adsorption configuration on
TiO2. In situ attenuated total reflectance Fourier transform infrared (ATR-FTIR)
spectroscopy results demonstrated that the polymerization of Si that formed on
the TiO2 surface compete with As adsorption sites, increasing the difficulty for
TiO2 regeneration. To effectively regenerate TiO2, the removal efficiency of Si
polymers on TiO2 via sodium fluoride (NaF) was studied. The results showed that
NaF could remove Si monomer and polymer from TiO2, and the regenerated TiO2 could
be reused with a stable adsorption performance. In situ ATR-FTIR spectroscopy
suggested that NaF desorbed the Si monomer and polymer effectively. When spent
TiO2 was regenerated with NaOH and NaF in three treatment cycles, As and Si
desorption rates were 86.8%-100.3% and 67.9%-82.0%, respectively. The present
study provides a new insight into regenerating absorbents with coadsorbed As and
Si in groundwater.
PMID- 29965470
TI - [Removal Efficiency and Mechanism of Removal by Humic Acid of the Integrated Floc
ultrafiltration Process].
AB - In recent years, the integrated ultrafiltration (UF) membrane process has been
widely used due to its high removal efficiency, slight membrane fouling, and
small land use. However, a number of problems gradually occurred regarding the
integrated UF process caused by the granular adsorbents used, such as powdered
activated carbon, carbon nano-tube, nanoscale zerovalent iron, etc. Severe
membrane surface damage was easily caused by these granular adsorbents after a
long running time, and the cost of most adsorbents was very high. In this study,
to effectively overcome these problems, cheap and loose aluminum hydrolyzed flocs
were directly injected into the membrane tank in the presence of humic acid (HA),
with the aim of investigating the removal efficiency of HA and the corresponding
membrane behavior. The results showed that the removal efficiency of HA could be
influenced by aeration mode, floc injection frequency, and floc dosage. Compared
with intermittent aeration and one-time injection, a loose "protection membrane"
layer was formed with continuous aeration and batch injections. Therefore, HA
molecules were largely removed, leading to the dramatic alleviation of membrane
fouling. The transmembrane pressure significantly increased to 74.8 kPa in the
absence of flocs after running for 5 days, but that only increased by 6.3 kPa
with continuous aeration and an injection frequency of once every 2 d (each
addition consisted of 5.4 mmol.L-1 flocs) after running for 8 days. The removal
efficiency of HA was 73.3% (8 d), which was much higher than in the absence of
flocs (5 d, 32.1%). Additionally, only a few HA molecules were adsorbed onto the
membrane pores with the batch injections, and a loose cake layer was the main
fouling mechanism. With higher dosages of flocs injected each time, the average
membrane pore diameter was larger after washing. Based on this excellent
performance, this floc-integrated UF membrane technology indeed shows large
application potential in water treatment.
PMID- 29965471
TI - [Emission Inventory of Greenhouse Gas from Urban Wastewater Treatment Plants and
Its Temporal and Spatial Distribution in China].
AB - Urban wastewater treatment plants are considered important greenhouse gas
resources with massive emissions of carbon dioxide (CO2), methane (CH4), and
nitrous oxide (N2O) during operation. Based on the emission factor approach of
pollutant reduction, the 2014 emission inventory of greenhouse gases (CO2, CH4,
and N2O) from urban wastewater treatment plants in China was established. In
addition, the temporal and spatial distribution and influencing factors of
greenhouse gas emissions were analyzed in this study. The results showed that
total emissions of greenhouse gas from urban wastewater treatment plants in China
was 7348.60 Gg (CO2-eq) in 2014, which included CO2, CH4, and N2O emissions of
6054.57 Gg, 27.47 Gg (769.08 Gg, CO2-eq), and 1.98 Gg (524.95 Gg, CO2-eq),
respectively. The difference in greenhouse gas emissions among provinces was
significant:high emissions appeared in the eastern areas of China, low emissions
were observed in the northwest, and hardly any emissions were found in Xizang.
From 2005 to 2014, annual greenhouse gas emissions from urban sewage treatment
plants in China increased by 229.4%, and the rates of CO2, CH4, and N2O increased
by 217.9%, 217.9%, and 520.3%, respectively. The regional economic development
level and number of wastewater treatment plants were correlated the most with the
emissions of greenhouse gasses, and the per-capita protein supply was closely
related with the N2O emission.
PMID- 29965472
TI - [Start-up and Operation of Biofilter Coupled Nitrification and CANON for the
Removal of Iron, Manganese and Ammonia Nitrogen].
AB - A pilot-scale bio-filter coupled nitrification and CANON was started up to remove
iron, manganese and ammonia nitrogen from groundwater in a plant, and the main
removal route of ammonia nitrogen was analyzed. The experiment showed that the
bio-filter could be started up successfully and achieved stable operation after
164 days of culture development. The value of ?NH4+-N/?NO3--N was 1.49, and the
oxidation and removal of Fe(II), Mn(II), and NH4+-N were (9.87+/-1.17), (2.25+/
0.06), and (1.51+/-0.06) mg.L-1, respectively. The calculation based on the
quantitative relationship between nitrogen conservation and dissolved oxygen (DO)
measurement indicated that the contribution of CANON to NH4+-N removal was 33.48%
38.87%, and the average ratio of ammonia nitrogen removal amount to DO was 1:3.79
1:3.94. The removal ratio of ammonia nitrogen was lower with lower temperature.
PMID- 29965474
TI - [Characteristics of Biofilm During the Transition Process of Complete
Nitrification and Partial Nitrification].
AB - The objective of the study was to investigate the change of biofilm
characteristics when implementing the procedure of partial nitrification. A ratio
control strategy (DO/NH4+-N) was taken to achieve partial nitrification, and
biofilm samples were obtained at 10.27%, 52.12%, and 93.54% of the nitrite
accumulation rate. The amount and spatial distribution of total bacteria, ammonia
oxidizing bacteria (AOB), and nitrite oxidative bacteria (NOB) were observed by
fluorescence in situ hybridization (FISH) and confocal laser scanning microscope
(CLSM) through a three-dimensional excitation emission matrix (EEM) to observe
the secretion and composition changes of extracellular polymer substances. Ratio
control successfully enriched AOB and achieved partial nitrification under
conditions when NOB was not completely washed. Heterotrophic bacteria and
nitrifying bacteria coexist in the biofilm. The heterotrophic bacteria were in
the outer layer, but nitrifying bacteria were distributed in the biofilm surface
at 6-25 MUm. During the process of short-range nitrification, the AOB/NOB value
gradually increased, and the stable operation period was as high as 15.56. During
the operation of the reactor, EPS and microbial flora changes are closely
related. When microbial activity decreased, EPS secretion decreased. During the
stable operation period of partial nitrification, NOB and other bacteria that are
non-resistant to high nitrite nitrous acid declined, and the fluorescence
intensity of aromatic protein-like bacteria decreased. However, the three
dimensional fluorescence spectra showed that the chemical composition of EPS was
not obvious during the process of partial nitrification.
PMID- 29965473
TI - [Analysis of CANON Process Start-up with Fiber Carrier].
AB - A CANON reactor with fiber carrier was started up by seeding nitrification sludge
and ANAMMOX sludge to study the operating characteristics of a fiber carrier. The
results showed that total nitrogen removal load rose from 0.09 kg.(m3.d)-1 to 0.9
kg.(m3.d)-1 and remained steady in the 85th day. This indicated that fiber
carrier is beneficial to the accumulation of sludge, and the reactor can maintain
a higher biomass. The DO in the reactor reached 5 mg.L-1 with the enrichment of
microorganisms, biofilm thickening, and the improvement of the reactor's ability.
The DO gradient of the biofilm from the outside to the inside was 0.32-0 mg.L-1,
which could be obtained by a microelectrode. It was shown that the permeability
of oxygen to the biofilm decreased, and the amount of nitrifying microorganisms
decreased with biofilm thickening. The quantitative PCR results showed that the
abundance of ANAMMOX was an order of magnitude more than before. The abundance of
AOB increased slightly, while the abundance of NOB stayed at a relatively low
level.
PMID- 29965475
TI - [Effect of Intermediate-Setting Aeration on the CANON Granular Sludge Process in
the AUSB Reactor].
AB - The impact of different aeration positions on startup and operation of the
continuous flow CANON granular sludge process was considered by inoculating
flocculent ANAMMOX activated sludge at room temperature (25+/-1)C in two sets of
AUSB reactors. The aeration unit of R1 was installed 0.3 m above the base, while
the aeration unit of R2 was set at the bottom. R1 and R2 successfully developed
the granule CANON process on the 43rd d and 56th d, respectively. The mean
particle diameter of R1 granular sludge increased to 214.79 MUm, and the
eigenvalue (?NO3--N/?TN) was maintained at 0.128; whereas, the granular sludge
size of R2 rose to 205.27 MUm with an eigenvalue maintained at 0.129. The
nitrogen loading rate (NLR) was gradually increased in the low ammonia-nitrogen
(90 mg.L-1) wastewater within R1 and R2. This was more beneficial in R1,
resulting in the persistent growth of CANON granular sludge and the enhancement
of the systematic nitrogen removal rate (NRR). The average particle diameter of
R1 rose to 507.46 MUm in 88 d, while NRR reached up to 0.277 kg.(m3.d)-1. R2
granule sludge particle size was 467.72 MUm after 108 d of cultivation, and
achieved a 0.243 kg.(m3.d)-1NRR, which was 87.73% of that in R1. During the
course of steady operation, the specific anoxic/aerobic mode of R1 effectively
suppressed NOB microbial activity, the eigenvalue remained around 0.127+/-0.003,
and the NRR of R1 was maintained at about (0.262+/-0.019) kg.(m3.d)-1. However,
NOB was propagated observably in the continuously aerobic R2, whose eigenvalue
rose to 0.136+/-0.004, while NRR was merely (0.231+/-0.015) kg.(m3.d)-1 after 125
d of long-term operation. During the whole experiment period, the intermediate
setting aerated AUSB accelerated the formation of CANON granular sludge evolving
from flocculent ANAMMOX sludge, and better nitrogen removal performance and
operational stability were achieved.
PMID- 29965476
TI - [Effect of Organic Carbon Source on Start-up and Operation of the CANON Granular
Sludge Process].
AB - The effect of organic carbon on the start-up and operation of the CANON granular
sludge process was investigated in two SBR reactors with different
strategies:gradually increased organic carbon concentration (R1) and without
organic carbon (R2). The results showed that adding 50 mg.L-1 organic carbon
accelerated the start-up of the CANON granular sludge process. R1 and R2 were
started up in 23 d and 32 d, respectively. Moreover, the appropriate organic
carbon enhanced the activity of AOB, AnAOB, and denitrification, increasing the
ammonia removal rates and total nitrogen (TN) removal rates. The maximum ammonia
removal rates and total nitrogen removal rates of R1 were 92% and 88%,
respectively. The maximum ammonia removal rates and total nitrogen removal rates
of R2 were 89% and 80%, respectively. Further tests showed that excessive organic
carbon concentration decreased the activity of AOB and AnAOB and reduced the
removal efficiency of ammonia and total nitrogen. Adding organic carbon promoted
denitrification activity and increased nitrogen removal efficiency.
PMID- 29965477
TI - [Start-Up and Regional Characteristics of a Pilot-scale Integrated PN-ANAMMOX
Reactor].
AB - The start-up and regional characteristics of a pilot scale integrated PN-ANAMMOX
reactor was studied. The results show that inoculated nitrosation suspension
filler in the anaerobic zone, ANAMMOX sludge, and common anaerobic sludge in the
anaerobic zone can start the reactor quickly. The PN-ANAMMOX reactor was
successfully started at 74 days. The removal rate of total nitrogen increased
from 0.02 kg.(m3.d)-1 to 0.48 kg.(m3.d)-1. The analysis of the nitrogen
conversion characteristics in two regions showed that the AOB had been in a
dominant position in the aerobic zone, and the NOB was inhibited by DO and the
matrix, NPRa increased from 0.22 kg.(m3.d)-1 to 0.58 kg.(m3.d)-1, and NAPa could
reach 95% with the increase in anaerobic denitrification capacity. The anaerobic
zone was a critical region of the integrated PN-ANAMMOX reactor, and NRRana
increased from 0.02 kg.(m3.d)-1 to 4.7 kg.(m3.d)-1. During the start-up period
(temperature decreased from 32C to 27C), the changes first affected the anaerobic
zone, NRRana decreased to 3.7 kg.(m3.d)-1 (about 21%), with little effect on the
aerobic zone. The two regions can achieve a large ANAMMOX bacteria enrichment,
as, during this time, the aerobic zone also has a certain denitrification
capacity, while the anaerobic zone featured enhanced denitrification.
PMID- 29965478
TI - [Effect of NOx--N Recycling Ratio on Denitrifying Phosphorus Removal Efficiency
in the ABR-MBR Combined Process].
AB - Based on the coupling of the ABR process and the MBR process, a novel combined
ABR-MBR process, including biophase separation, liquid circulation, and
functional linkage, was developed to achieve simultaneous carbon, nutrient, and
phosphorus removal when treating domestic wastewater with low carbon/nitrogen
ratio and to obtain the best combination of ABR, providing a quality carbon
source, and MBR, achieving shortcut nitrification by optimizing hydraulic
retention time (HRT). The influence of NOx--N recycling ratio on nitrogen and
phosphorus removal was investigated at NOx--N recycling ratios of 100%, 200%,
300%, and 400%, respectively. The experimental results under different conditions
showed that the efficiency of denitrifying phosphorus removal in the ABR was
found to increase with increasing NOx--N recycling ratio from 100% to 300% but
decreased when the NOx--N recycling ratio was 400%. Shortcut nitrification was
achieved by controlling the low dissolved oxygen (DO) concentration ranges from
0.3 to 1.0 mg.L-1 with the short HRT of 3 h in the MBR reactor. The nitrite
accumulation ratio was above 60%, when the NOx--N recycling ratio was 300%.
Meanwhile, shortcut denitrifying phosphorus removal (where NO2--N mainly acted as
the electron acceptor for denitrifying phosphorus removal) was achieved and
played the dominant role in phosphorus removal.
PMID- 29965479
TI - [Effects of Magnetic Fe3O4 Nanoparticles on the Characteristics of Anaerobic
Granular Sludge and Its Interior Microbial Community].
AB - In this study, the effects of magnetic Fe3O4 nanoparticles (Fe3O4 NPs) on soluble
microbial products (SMP), loosely bound extracellular polymeric substances (LB
EPS), and tightly bound extracellular polymeric substances (TB-EPS) in anaerobic
granular sludge were examined. In addition, the anaerobic granular sludge
interior microbial community dynamics were investigated using high-throughput
sequencing. The results demonstrated that the removal rate of COD was 83.6% after
long-term exposure in the experimental reactor, namely, the anaerobic reactor
containing Fe3O4 NPs. It was reduced by 5.7% in comparison with the removal rate
in the control reactor. The total amount of TB-EPS in anaerobic granular sludge
in the experimental and control reactors was 178.20 mg.g-1 and 138.24 mg.g-1,
respectively, while the total amount of SMP in anaerobic granular sludge was
34.88 mg.L-1 and 27.44 mg.L-1, respectively. With regard to the LB-EPS in
anaerobic granular sludge in the experimental reactor, the peak of humic acid
disappeared and the peak intensity of coenzyme F420 decreased slightly using
excitation-emission matrix (EEM) fluorescence spectra. In terms of the microbial
community dynamics in the experimental reactor, the abundance of Methanobacterium
was greatly augmented from 76.15% to 86.76%; whereas, the abundance of
Methanothrix decreased from 17.1% to 7.51%. This indicated that Methanothrix was
more sensitive to Fe3O4 NPs. Moreover, the changes in bacterial communities were
evident:1the abundance of Proteobacteria dropped from 66.44% to 47.16%; 2 the
abundance of Actinobacteria grew from 8.97% to 17.33%; and 3 the abundance of
Bacteroidetes increased from 8.07% to 17.74%. The increasing abundance of
Actinobacteria and Bacteroidetes plays a positive role in the anaerobic
hydrolysis of organic matter.
PMID- 29965480
TI - [Characterization Composition of Soluble Microbial Products in an Aerobic
Granular Sludge System].
AB - Using flocculent activated sludge as seed sludge to cultivate aerobic granular
sludge in a SBR, the main objective of this study was focused on the
accumulation, relative molecular mass distribution, and composition of soluble
microbial products (SMP) in an aerobic granular sludge (AGS) system. SMP were
predominant (71-85 mg.L-1) in the effluent of the AGS system. The formation of
SMP was related to substrate utilization, biomass decay, and EPS hydrolysis. A
relative molecular mass distribution analysis indicated that the majority of SMP,
accounting for about 54.8%-71.7%, had Mr<3*103; whereas, the Mr>100*103 formed a
small fraction, constituting only 9.3%-14.5%. Three-dimensional excitation
emission matrix fluorescence spectra (3D-EEM) identified four peaks in SMP,
belonging to aromatic protein-like, tryptophan protein-like, humic acid-like, and
fulvic acid-like substances. Gas chromatography-mass spectrometry (GC-MS)
analysis revealed that esters (39.0%), short chain alkanes (14.9%), alkenes
(11.7%), and alcohols (7.6%) were the main compounds in SMP. Most notably, bis(2
ethylhexyl) phthalate, as one kind of ester, accounted for 32% of the identified
SMP.
PMID- 29965481
TI - [Influence of Ciprofloxacin on the Microbial Community and Antibiotics Resistance
Genes in a Membrane Bioreactor].
AB - A membrane bioreactor (MBR) was used to treat ciprofloxacin (CIP)-contaminated
artificial wastewater. The microbial community structure and the abundance of
antibiotic resistant genes (ARGs) in the MBR were studied at four CIP dosages (0,
5 mg.L-1, 10 mg.L-1, and 15 mg.L-1). The results showed that Proteobacteria and
Bacteroidetes remained the dominant phylum, with relative abundances of 57.5% and
12.7%, respectively, as the dosage of CIP was increased from 0 mg.L-1 to 15 mg.L
1. Rhodocyclaceae, Chitinophagaceae, and Comamonadaceae became the dominant
family with abundances of 29.96%, 5.44%, and 6.60%, respectively.
Methyloversatilis, Ferruginibacter, Zoogloea, and Comamonas became the dominant
genus, with relative abundances of 21.70%, 7.56%, 5.24%, and 4.15%, respectively.
The decrease of Chao1, ACE, and Shannon and the increase of Simpson indicated a
decrease in microbial abundance and diversity. The relative abundances of
Nitrosomonas, Nitrospira, Alcaligenes, and Nitrobacter decreased, which caused a
decrease in the NH3-N removal rate. A CIP-ARGs analysis revealed that the
relative abundances of gyrA, gyrB, and parC were increased, beginning after the
sludge was dosed with 5 mg.L-1of CIP for 33 days, which augmented the risk for
microbial drug-resistance.
PMID- 29965482
TI - [Analysis of Low C/N Wastewater Treatment and Structure by the CEM-UF Combined
Membrane-Nitrification/Denitrification System].
AB - In this study, a CEM-UF composite membrane with ammonia nitrogen enrichment and
separation characteristics was combined with nitrification/denitrification to
treat low C/N wastewater. The denitrification characteristics of low C/N
wastewater at different flow ratios were investigated, and the structural
characteristics of functional microbial communities in nitrifying and
denitrifying activated sludge were analyzed by 16Sr DNA high-throughput
sequencing. The results showed that influent TN was 60 mg.L-1, COD/TN was 2.65,
the nitrification effect of each flow rate was good, and the average ammonia
nitrogen removal rate was 98.7%. When the flow ratio increased from 1:2 to 1:6,
the m(COD)/m(NO3--N) of denitrification was increased, and the removal of average
nitrate nitrogen reached its highest level at 1:6, which was 86.28%, and the
removal of total nitrogen increased from 22.56% to 46.8%. An analysis of Illumina
sequencing showed that nitrogen fixing bacteria Proteobacteria accounted for
30.9%, and the important nitrite oxidizing bacteria, Nitrospirae, accounted for
3.06%. At the genus level, Nitrosomonas and Nitrosospira, belonging to the
ammonia oxidizing bacteria (AOB) category and Nitrospira and Nitrobacter,
belonging to the nitrite oxidizing bacteria (NOB) category were detected. The
ratio of AOB and NOB bacteria was high, which is consistent with good
nitrification in the nitrification reactor. The dominant bacteria in
denitrification sludge were Proteobacteria (53.13%), followed by Bacteroidetes
(10.93%). A variety of bacteria related to denitrification were detected at the
genus level, such as Dechloromonas, Thauera, Castellaniella, Alicycliphilus,
Azospira, Comamonas, Caldilinea, and Saccharibacteria. The proportion of
denitrifying bacteria was 25.91% as denitrifying bacteria microbial species were
rich in the denitrifying sludge, giving a good denitrification effect.
PMID- 29965483
TI - [Effects of Phosphorus on the Activity and Bacterial Community in Mixotrophic
Denitrification Sludge].
AB - Biological denitrification is now one of the most widely applied techniques to
remove nitrogen from the aquatic environment, and mixotrophic denitrification has
gained attention as it takes the characteristics of both heterotrophic and
autotrophic denitrification. This study investigated the biological
denitrification efficiency and the bacterial community structure of sludge
sampled from a mixotrophic denitrification reactor, before and after adding a
certain amount of phosphate. The results showed that the bacteria have the
capability of denitrification even without phosphorus, but the addition of
phosphorus could significantly improve the biomass and the denitrification
activity. After phosphate was added, the autotrophic and heterotrophic
denitrification activity increased to 0.056 mg.(L.min.g)-1 and 0.232 mg.(L.min.g)
1 on N/VSS, which was 2.9 and 3.9 times that of the sludge activity before
phosphorus addition, respectively. The bacterial community structure illustrated
that the denitrifiers increased remarkably from 13.47% to 44.82% and that the
dominate bacteria have also changed. Meanwhile, the growth of autotrophic,
heterotrophic, and mixtrophic bacteria were all improved significantly after
phosphorus was added.
PMID- 29965484
TI - [Acclimatization and Community Structure Analysis of the Microbial Consortium in
Nitrate-Dependent Anaerobic Methane Oxidation].
AB - Methane oxidation coupled with denitrification is an effective way to reduce the
discharge of nitrate and methane. The anaerobic sludge from a laboratory
wastewater treatment facility, anaerobic sludge from a wastewater treatment
plant, and soil from a landfill were selected as inoculum to enrich the
consortium for anaerobic methane oxidation in cooperation with nitrate reduction.
The investigation of methane oxidation was carried out in these systems. The
results showed that the maximum methane consumption rate of 0.05 mg.d-1 was
obtained when the anaerobic sludge from a wastewater treatment plant served as
inoculum. The population of bacteria and archaea were assayed by the clone
library method. The Methanosarcinales and Methanomicrobiales were present in
methane oxidation as methane oxidizing archea. The Pseudomonas, Clostridia, and
Thermomonas were identified as nitrate reducing bacteria in the process of
nitrate reduction. Both the methane conversion rate and microbial population
varied with the amount of nitrate. The nitrate reduction bacteria were
Pseudomonas and Clostridia when the nitrate concentration was 200 mg.L-1. The
Pseudomonas and Thermomonas emerged when the nitrate concentration increased to
500 mg.L-1, and the rate of methane conversion was increased by 34.7%. The
results provided science evidence for the co-treatment of methane and nitrate.
PMID- 29965485
TI - [Diffusion of Microorganism and Main Pathogenic Bacteria During Municipal Treated
Wastewater Discharged into Sea].
AB - Numerous microorganisms, especially pathogens, exist in treated wastewater, which
leads to possible risk to population health and marine ecological security when
treated wastewater is discharged into the sea. This study selects Maidao
municipal sewage treatment plant as the location. The microbial community and the
dynamic distribution and seasonal variation of pathogens are analyzed by high
throughput sequencing technology. The results showed that the microbes in the
discharge were distributed into 20 to 27 phyla, and the dominant phyla were
Proteobacteria, Firmicutes, and Bacteroidetes, which were mainly distributed in
44 to 65 classes. The predominant pathogens are mainly composed of
Gammaproteobacteria, Betaproteobacteria, and Epsilonproteobacteria in the
Proteobacteria category. The proportion of most dominant phyla and classes in the
sample decreased with an increase in diffusion distance. There were mainly 55
species pathogenic bacteria in the water discharging into the sea. The pathogenic
genes in the discharge were mainly related to cancer, cardiovascular disease,
immune system diseases, infectious diseases, metabolic diseases, and
neurodegenerative diseases. When compared with the blank samples, it was found
that the biomass of pathogenic bacteria decreased sharply with the diffusion by
the seawater, and most of the pathogens were not detected 1000 m away from the
seashore. Arcobacter spp. caused human and animal diarrhea and bacteremia,
Acinetobacter spp. caused nosocomial infections, and Shewanella hafniensis posed
a threat to seafood farming and fishing. The three species of pathogenic bacteria
mentioned above occupied a fairly large proportion of the discharge into the sea.
PMID- 29965486
TI - [Oxytetracycline Wastewater Treatment in Microbial Fuel Cells and the Analysis of
Microbial Communities].
AB - Oxytetracycline (OTC) as an important broad spectrum antibiotic has been widely
used in animal husbandry. However, the abuse of OTC not only has a direct adverse
impact on ecosystems, but also exacerbates the appearance of antibiotic
resistance bacteria and antibiotic resistance genes. OTC-containing wastewater
was treated using microbial fuel cells (MFCs), and the removal efficiency of OTC
in MFCs in different operation periods was investigated. Result showed that the
removal efficiency of 10 mg.L-1 OTC by MFCs within 132 h was up to 99.0% after
150 d of operation. The bacterial communities in raw pig mature and anodic
biofilms were studied by high-throughput sequencing. This showed that Firmicutes
were both dominant on phylum a level; However, compared to the raw pig mature,
the abundance of Proteobacteria greatly increased from 2.84% to 8.92%-22.75% in
the anodic biofilm. In addition, the abundance of Eubacterium spp. in the anodic
biofilm increased obviously from nearly 0.00% to 20.49%-49.00%. It has been
reported that some Eubacterium spp. were able to biodegrade oxygen heterocyclic
aromatic compounds contained in OTC. Therefore, Eubacterium spp. is suggested as
potential functional species in the biodegradation of OTC and/or its metabolites.
This work proves the feasibility and effectiveness of removing OTC-containing
wastewater by using MFCs.
PMID- 29965487
TI - [Spatial and Temporal Variability of Soil C-to-N Ratio of Yugan County and Its
Influencing Factors in the Past 30 Years].
AB - The soil carbon-to-nitrogen (C/N) ratio of soils is a sensitive indicator of soil
quality and an indicator for assessing the carbon and nitrogen nutrition balance
of soils. Its variation is significant in reflecting the carbon and nitrogen
cycling of soils. An accurate knowledge of how the C/N ratio varies spatially and
temporally and the driving factors at county scale is of great significance to
the extrapolation of balanced fertilization based on soil C/N ratio regulation as
well as to the protection of the ecological environment. This study was based on
200 points of surface soil samples (0-20 cm) collected during the second National
Soil Survey in 1982 and 423 points of surface soil samples (0-20 cm) collected
during the soil test-based formulated fertilization project in 2012 in Yugan
County. Combined with the soil parent material, soil type, farmland-use type,
terrain factors, pH, straw incorporation pattern, and nitrogen fertilizer rate
over the past 30 years, spatial and temporal variability characteristics of the
soil C/N ratio were analyzed by using ordinary kriging methods, and the effects
of the influencing factors were quantified by regression analysis. The results
indicated that the mean value of the C/N ratio was 10.05 and 11.18 in 1982 and
2012, respectively. The coefficient of variation was 19.40% and 25.04%,
respectively, which suggested the soil C/N ratio had moderate variability in the
study area. The ratios of nugget to sill were 15.91% and 71.25% in 1982 and 2012,
respectively. This means that the leading factor from the structural factors
(parent material and soil type) into the stochastic factors (nitrogen fertilizer
rate and straw incorporation pattern). In the past 30 years, most of the regional
soil C/N ratio increased significantly especially the eastern region. The spatial
variability of soil C/N in 1982 was mainly affected by soil parent material, soil
type, terrain factor, and pH, with the degree of influence of each variable at
17.3%, 14.2%, 7.4%, and 2.3%. In 2012, the spatial variability was mainly
affected by soil parent material, soil type, farmland-use type, terrain factor,
straw incorporation pattern, and nitrogen fertilizer rate, with the degree of
influence of each variable of 8.7%, 23.5% 28.2%, 12.2%, 12.6%, and 42.3%,
respectively. To maintain the steady growth of the soil C/N ratio, it is
suggested that the return of carbon be incorporated with the input of nitrogen,
such as incorporating crop residues into the soil and inputting more organic
fertilizers into the soil in future farming practices.
PMID- 29965488
TI - [Spatial Heterogeneity of Soil Carbon and its Fractions in the Wolfberry Field of
Zhongning County].
AB - It is important to accurately assess the regional spatial distribution and
variation of soil carbon and its fractions due to its great significance in soil
carbon cycling and soil quality. The objectives of this study were to investigate
the spatial variability of soil carbon and its fractions using classical and
geostatistical statistics. Topsoil samples (0-20 cm) from 119 sites in Wolfberry
Field were collected from a grid of 100 m*100 m in Zhongning County. The GS+7.0
software was used to fit a semivariance model to determine the optimal
theoretical model and parameters. The spatial distribution characteristics of
soil carbon and its fractions were studied by ordinary kriging. The classical
statistical analyses showed that the average concentrations of total carbon,
inorganic carbon, organic carbon, active organic carbon, medium active organic
carbon, and high active organic carbon were 28.74, 18.72, 10.09, 1.81, 1.48, and
0.73 g.kg-1, respectively. The variation coefficient of total carbon and
inorganic carbon were 7.69% and 9.13%, indicating a strong variation, while the
other soil carbon fractions showed moderate variation with the coefficients of
variations ranging from 14.77%-52.05%. The geostatistical analyses revealed that
the semivariogram of organic carbon was best fit by the spherical model, while
the other five kinds of carbon fractions were best fit by the exponential model.
The nugget coefficients of total carbon and organic carbon were 48.99% and
34.35%, which demonstrated moderate spatial dependence. The nugget coefficients
of inorganic carbon, active organic carbon, medium active organic carbon, and
high active organic carbon were 8.17%, 0.25%, 12.18%, and 0.08%, which
demonstrated strong spatial dependence. The ordinary kriging interpolation map
indicated that the spatial distribution patterns were similar for total carbon,
organic carbon, medium active organic carbon, and high active organic carbon,
which increased from southeast to northwest. Inorganic carbon and active organic
carbon presented an irregular plaque distribution in the study area. Spatial
interpolation maps could provide useful information for environmental management
and the sustainable use of land resources in this region.
PMID- 29965489
TI - [Response of Soil Enzyme Activities and Their Relationships with Physicochemical
Properties to Different Aged Coastal Reclamation Areas, Eastern China].
AB - Land reclamation transforms a tidal flat from a marine ecosystem to terrestrial
ecosystem, which significantly changes the soil ecosystem process, affecting the
soil enzyme activities. Soil enzyme is involved in almost all soil biochemical
processes. Clarifying the relationship between soil physicochemical properties
and soil enzyme activities can reveal the changes of soil quality after
reclamation and provide a theoretical basis for the scientific regulation of the
soil ecosystem. In this study, a total of 72 soil samples were collected from a
coastal reclamation area with different years of reclamation (0, 7, 32, 40, and
63 a) in Rudong County. The changes in soil physicochemical properties and enzyme
activities within different reclamation years were analyzed by classical
statistical analysis, and the relationship between soil enzyme activities and
physicochemical properties was analyzed using a redundancy analysis. The results
showed that longterm land reclamation had significant effects on soil
physicochemical properties and enzyme activities. pH and electrical conductivity
showed a decreasing trend after reclamation, while the content of soil organic
carbon, total nitrogen, and total phosphorus showed a trend of "rapidly
accumulate-gradually consume-accumulate again" with increasing years of
reclamation. Compared with the bare flat area (0 a), amylase, dehydrogenase, and
acid phosphatase activity initially increased and then decreased with increasing
years of reclamation, while urease and alkaline phosphatase activities were
characterized by an increase-decrease-increase trend. Meanwhile, the enzyme
activities within different reclamation ages were basically higher in surface
soil than deep layers. Redundancy analysis revealed that the soil physicochemical
properties explained 69.8% of the variation in soil enzyme activities, and an
obvious relationship existed between pH, electronic conductivity, soil organic
carbon, total nitrogen, total phosphorus, and soil enzyme activities (P<0.01).
The order of importance of soil physicochemical properties to soil enzyme
activities was as follows:total nitrogen > soil organic carbon > pH > total
phosphorus > electronic conductivity.
PMID- 29965490
TI - [Distribution, Sources, and Ecological Risk Assessment of Polycyclic Aromatic
Hydrocarbons (PAHs) in Soils of the Central and Eastern Areas of the Qinghai
Tibetan Plateau].
AB - Fifty-five soil samples were collected across the central and eastern Qinghai
Tibetan Plateau during July to August in 2013. These were analyzed for the
sixteen polycyclic aromatic hydrocarbons (PAHs) called out by the USA EPA. The
concentration characteristics, sources, and potential ecological risk assessment
of the sixteen PAHs in the soils were investigated. The soils were extracted by
ultrasonic extraction, purified by an HLB solid-phase extraction column, and
quantified by gas chromatography-mass spectrometry (GC-MS). The total PAH
concentrations ranged from 40.47 to 1276.40 MUg.kg-1, with a mean of 267.97
MUg.kg-1. Low-ring PAHs (two and three rings PAHs) were dominant in all samples,
and the proportion of phenanthrene was the highest. The sources of PAHs were
assessed by diagnostic ratios and a principal component analysis (PCA), which
indicated that the main sources of the PAHs originated from petroleum and biomass
combustion. The toxic equivalent concentration (TEQ) concentration of benzopyrene
(a)-pyrene (TEQBaP) in soils ranged from 3.73 to 79.32 MUg.kg-1, with an average
concentration of 12.84 MUg.kg-1. The TEQBaP in 4% of the soil samplings exceeded
the Dutch target reference value (33.00 MUg.kg-1), suggesting that a small
portion of the soils in the Qinghai-Tibetan Plateau have potential ecological
risk.
PMID- 29965491
TI - [Source Apportionment of Heavy Metals in Farmland Soils Around Mining Area Based
on UNMIX Model].
AB - Forty-two farmland soil samples were collected from the mining area of Huize
City, Yunnan Province, to identify the sources of metals in the farmland soils,
and 14 selected elements in farmland soils were detected. The UNMIX model was
applied to identify the sources of the metals. The inverse distance weighted
interpolation method of statistical analysis in ArcGIS was used to develop a
spatial distribution map of the six severely polluted metals to validate the
source apportionment results of the UNMIX model. The results indicated that:1 the
metals, Pb, Zn, and Cd, in the studied farmland soils were seriously polluted
according to the soil background values of Yunnan Province and the Chinese
environmental quality standard; 2 there were three potential sources of metals
according to UNMIX model:source 1 was the anthropogenic sources caused by
industrial activities with a source contribution rate of 16.32%; source 2 was the
anthropogenic sources caused by coal combustion and fertilization with a source
contribution rate of 68.26%; and source 3 was the combined sources caused by
mining related activities and soil parent materials with a source contribution
rate of 15.42%; and 3 the spatial distribution of selected metals was in
accordance with the local land-use and the results of the UNMIX model. Therefore,
the UNMIX model can be effectively applied to the source apportionment of heavy
metals in farmland soils around the mining area.
PMID- 29965492
TI - [Stabilization Effects of Fe-Mn Binary Oxide on Arsenic and Heavy Metal Co
contaminated Soils Under Different pH Conditions].
AB - pH is one of the most important factors affecting speciation and stabilization of
arsenic and heavy metals in soil. In this study, Fe-Mn binary oxide (FMBO),
synthesized by redox and precipitation reactions, was taken as the research
object to evaluate its stabilization effects on As, Pb, Cd, Zn, and Cu in three
types of soils under different pH conditions and to study the impacts on soil pH
and buffering capacity. The results showed that the leaching concentrations of As
and Pb were lower in the pH range of 3-9 (neutral and weak acidic) and 5-10
(neutral and weak alkaline); and Cd, Zn, and Cu were stable in the pH range of 7
11 (alkaline). The stability and stabilization effects of FMBO were better under
alkaline conditions than acidic. In the optimal pH range, the optimum
stabilization efficiency of FMBO could reach 92.7%, 100%, 97.0%, 88.7%, and 82.7%
for As, Pb, Cd, Zn, and Cu, respectively. In addition, FMBO addition could
increase soil pH and the acid buffering capacity moderately, which improved heavy
metal stabilization and made it more suitable for acid soils and areas with more
acid rain. From the correlation of contaminants and soil elements in the
leachates, Fe played an important role in As stabilization, and pH had a great
influence on the stabilization of Pb, Cd, Zn, and Cu.
PMID- 29965493
TI - [Concentration and Distribution of Novel Brominated Flame Retardants in Human
Serum from Three Chinese Cities].
AB - Four novel brominated flame retardants (NBFRs), hexabromobenzene (HBB),
pentabromotoluen (PBT), pentabromophenyl (PBBz), and tetrabromo-p-xylene (PTBX),
were found in human serum samples pooled by donor age (>= 60, 50-59, 40-49, 30
39, and 20-29 years old) and supplied by Yitong (YT, Jilin Province), Ganzi (GZ,
Sichuan Province), and Huaihua (HH, Hunan Province). PBBz, PBT, and HBB were
found in each of the pooled samples. The total NBFRs concentration in YT and HH
were higher than the concentration found in GZ. The concentrations of total
NBFRs, HBB, PBT, and PBBz (except GZ) were elevated in young people. In both YT
and HH, the main pollutants were found in the five age groups; however, the main
pollutants in GZ were not obvious, and the concentration ratios of four of the
NBFRs were basically stable in the five age groups. The distribution of NBFRs in
human serum in the three cities showed different trends in the five age groups,
which indicated different sources of pollution in different areas. The total
concentrations of NBFRs in the industrially developed areas (YT and HH) were
higher than that in the less developed areas (GZ).
PMID- 29965494
TI - [Estimation of Fine Particle (PM2.5) Emission Inventory from Cooking: Case Study
for Shanghai].
AB - Cooking is one of important emission sources of fine particles (PM2.5). This
study using the catering enterprises of Shanghai as an example, presents a method
to estimate the PM2.5 emission inventory from cooking according to the number of
stoves, cooking time, and number of customers. Based on in situ measurements, the
concentrations of PM2.5 emissions ranged from 0.1 mg .m-3 to 1.8 mg .m-3, which
exceeded the limit (1.0 mg .m-3 for lampblack) in the national standard. Organic
carbon dominated the PM2.5 emitted from cooking, accounting for more than 50%.
Extremely high ratios of organic carbon to elemental carbon were observed,
ranging from 58.8 to 752.3, which could be used as an indicator of cooking
emissions. The emission factors of PM2.5 in the catering industry are closely
related to the scale of the catering enterprises. The emission factors of large
and medium-sized enterprises are obviously higher than those of small and micro
enterprises. The PM2.5 emissions of catering enterprises are mainly attributed to
high emission loads of large enterprises and those for a large number of small
and medium enterprises. The PM2.5 emission inventory of cooking in Shanghai was
calculated according to the three emission factors above, and the results were
very close. Therefore, the method for estimating the PM2.5 emission inventory for
cooking presented in this study is helpful for other Chinese cities to calculate
their PM2.5 emission inventory from cooking.
PMID- 29965495
TI - [Chemical Characterization, Spatial Distribution, and Source Identification of
Organic Matter in PM2.5 in summertime Shanghai, China].
AB - Particulate organic matter (POM) has attracted increasing attention recently due
to its great contribution to fine particles (PM2.5) and complex components and
sources. In the present study, 78 particulate organic compounds in PM2.5 were
quantified at three sites in Shanghai during summer; these sites were located in
urban (Xuhui), suburban (Qingpu), and coastal (Lin'gang) areas of the city.
Accordingly, the chemical composition and spatial distribution were investigated
and sources were explored based on the indicators and diagnostic ratios combined
with backward trajectory. The results showed that during the period of
observation, the quantified organic matter in the suburban area is about 319 ng
.m-3, close to the urban area but much higher than that of the coastal areas.
Fatty acids were the largest contributors, followed by levoglucosan, polycyclic
aromatic hydrocarbons (PAHs), n-alkanes, and hopanes. Source analysis based on
tracer methods indicates that gasoline vehicle emissions were the main source of
POM in Shanghai. Biomass burning from the northeast impacted somewhat on the
urban area and western suburbs during the observation period. Terrestrial plant
emissions played an important role in the source of fatty acids at Qingpu and
Lin'gang, and emissions of marine phytoplankton and microorganisms were also
important for fatty acids at Lin'gang. Coal combustion and motor vehicle exhaust
made an important contribution to PAHs according to an analysis of diagnostic
ratios. This study presented the characteristics and sources of POM in summertime
Shanghai, which facilitates the development of an effective control strategy on
PM2.5 pollution.
PMID- 29965496
TI - [Seasonal Variation and Source Analysis of Water-soluble Inorganic Salts in PM2.5
in the Southern Suburbs of Beijing].
AB - In order to study the variation of water-soluble inorganic ions in the four
suburbs of Beijing using the atmospheric fine particulate matter rapid trapping
system and chemical composition analysis system (RCFP-IC), we carried out
measurements for nine water-soluble inorganic ions (Cl-, NO2-, NO3-, SO42-, Na+,
NH4+, K+, Mg2+, Ca2+) in PM2.5 with continuous on-line observations for one year
in Beijing's southern suburbs in 2016. The transport process of pollutants and
the potential sources of pollutants were evaluated by combining a trajectory
clustering method and potential source contribution factor analysis method
(PSCF). During the observation period, the total concentration of the nine water
soluble inorganic ions was 38.6 MUg .m-3, and results showed that the
concentration in winter and spring was high and in summer and autumn was low. The
order of the concentration from high to low was SO42- > NO3- > NH4+ > Ca2+ > NO2-
> Cl- > Na+ > K+ > Mg2+. In winter, the SO42-, NO3- and NH4+ accounted for 75.7%
of the total measured water-soluble ions, followed by 72.8% in spring and 60.2%
in summer. With an increase in air pollution, the concentrations of SO42-, NO3-,
and NH4+ increased significantly, indicating that SO42-, NO3-, and NH4+ were
closely related to the deterioration of air quality. SO42- was dominant in the
formation of secondary ions compared to NO3- and NH4+; and SO42-, NO3-, and NH4+
had significant diurnal variations. The diurnal variation of the SO42- statistic
(hours) was bimodal, and the peak values were at about 10:00 and 18:00. The
diurnal variation of NO3- and NH4+ had single peaks, with the peak appearing at
10:00. The trend of the diurnal variation for these two ions was similar.
Finally, the sources of pollution in the southern suburbs of Beijing mainly
included secondary sources, coal-fired sources, and mixed sources of dust and
dust. The main potential source of pollution in the southern suburbs was in the
southeastern part of the observation site, while the northeastern airflow was
favorable for the diffusion and dilution of pollutants.
PMID- 29965497
TI - [Characteristics and Source Apportionment of Water-soluble Inorganic Ions in Road
Dust PM2.5 During Spring in Tianjin Using the Quadrat Sampling Method].
AB - In order to collect comprehensive information regarding the characteristics and
sources of the water-soluble inorganic ions in road dust (RD) PM2.5 in Tianjin,
samples of road dust were collected in April 2015 in Tianjin, and then re
suspended on filters using a NK-ZXF sampler. The concentrations of the major
water-soluble inorganic ions were analyzed by ion chromatography. A correlation
analysis, ratio method, and principal component analysis were used to analyze the
sources of RD PM2.5. The results showed that the total water-soluble inorganic
ion concentration in Tianjin accounted for 6.13%+/-2.32%, varying with different
road types. Na+, K+, Mg2+, and Ca2+ showed high homology. NO3-/SO42- revealed
that the main source of PM2.5 was mostly attributed to fixed sources. The
principal component analysis showed that the main sources of RD PM2.5 in Tianjin
were coal combustion, mobile sources, biomass burning, and construction dust.
PMID- 29965498
TI - [HONO Pollution Characteristics and Nighttime Sources During Autumn in Guangzhou,
China].
AB - Nitrous acid (HONO) plays an important role in atmospheric photochemistry
processes because its photolysis provides an efficient source of hydroxyl (OH)
radicals in the troposphere. However, few studies exist on HONO in nocturnal
chemistry processes. Using the observation data of HONO and related parameters
for a super site at Guangzhou Jinan University in October 2015, the pollution
processes and sources of HONO during nighttime were analyzed in this study. The
results showed that the average concentration of HONO was 4.32 MUg .m-3 during
the nighttime, which was 2.6 times its concentration of 1.67 MUg .m-3 in the
daytime. The conversion rate of HONO, CHONO, during the nighttime was 0.0068 h-1,
and the average contribution of vehicle emissions to HONO was 15.1%, with a peak
of 37.8% at 20:00. The average net HONO generation rate from the reaction of NO
and OH radicals during the night was 0.44 MUg .(m3 .h)-1. Correlation analysis
suggested that particles could not be the major HONO source, but that relative
humidity (RH; 33%-78%) was a key factor. Relevant calculation indicated that the
heterogeneous reaction of deposited NO2 on humid ground surfaces could be the
main source of HONO during nighttime.
PMID- 29965499
TI - [Sulfur Sources and Oxidation Pathways in Summer Aerosols from Nanjing Northern
Suburbs Using S and O Isotopes].
AB - The sulfur and oxygen isotopic compositions of sulfate in PM2.5 were determined
by EA-IRMS to study the sulfur sources and oxidation formation pathways of
sulfates in PM2.5 from Nanjing northern suburbs during July 2014. The results
indicated that delta34 S values of sulfate ranged from 1.70/00 to 4.80/00 with an
average of 3.20/00+/-1.00/00, while delta18O values ranged from 7.50/00 to
12.90/00 with an average of 9.30/00+/-1.70/00. Comparing the delta34 S values of
aerosol sulfate and potential pollution sources, we concluded that the sulfur
source of PM2.5 was mainly local coal combustion and vehicle exhaust. In
addition, the secondary sulfate was dominant in PM2.5, and 59.3% of the formation
of the secondary sulfate was caused by SO2 homogeneous oxidation. In addition,
the heterogeneous oxidation of SO2 in the atmosphere was dominated by ferrous
iron oxidation in excess O2. The main mechanisms of homogeneous oxidation include
oxidation in the presence of electric discharge (presumably forming O3) and NO2.
PMID- 29965500
TI - [Methods for Determining and Applications of High-Resolution Vehicle Emission
Inventory at County Scale].
AB - This study proposes a method for high-resolution vehicle emission inventories at
county scale based on field investigations and Google Earth satellite images,
using the Tongzhou district of Beijing as an example for data analysis. VKT and
the corresponding emissions of each pollutant were calculated using the number of
registered vehicles and the real-time traffic volumes, respectively. The results
showed that the mileage calculated based on the method using registered vehicles
is about 37% less than that based on real-time traffic volumes, with the latter
method providing data closer to the actual situation. The mileage for small
passenger cars, large passenger vehicles, and medium-duty trucks were
underestimated, and that for light trucks, heavy trucks, low-speed trucks were
overestimated based on the registered vehicle method. Emissions from small
passenger cars were also underestimated by about 51%, using the registered
vehicle method. For emissions of large passenger vehicles, light trucks, and
medium-duty trucks, there was less difference between the two methods. Based on
the registered vehicle method, emissions of heavy trucks, low-speed trucks, and
motorcycles were overestimated by about 41%, 30%, and 30%, respectively.
PMID- 29965501
TI - [Characteristics of Polycyclic Aromatic Hydrocarbons Emitted from Typical
Industrial Biomass Boilers].
AB - This research selected 13 types of industrial biomass boilers and used GC-MS
technology to investigate the characteristics of 15 polycyclic aromatic
hydrocarbons (PAHs) emitted from the boils. The results show that the total
emissions of the 15 PAHs was 0.02-27.8 g .h-1, and the concentration was 0.77
3173 MUg .m-3. There was a large different in the Sigma15 PAHs concentration and
emissions for each boiler. The maximum concentration appeared in the No.13 boiler
sample, and the maximum emissions appeared in the No.4 boiler sample; these have
relatively high concentrations of PAHs and large stack gas velocities. PAHs were
found to be dominant in the gas phase, with a proportion of 45.9%~100%.
Acenaphthylene, phenanthrene, fluoranthene, and pyrene were the main PAHs. The
spectral distribution profiles of the 15 PAHs were similar, and the general
concentrations were C3,4 rings > C5,6 rings. Diagnostic ratios the fluoranthene
to fluoranthene plus pyrene (Flu/(Flu+Pyr)) from biomass combustion were greater
than 0.5, except for the No.4 sample, which was 0.4. There were obvious positive
interrelationships between O2 and acenaphthylene, acenaphthene, phenanthrene, and
anthracene. In addition, there were obvious interrelationships between CO and
indeno[1,2,3-cd]pyrene, benzo (g,h,i) perylene, and acenaphthene.
PMID- 29965502
TI - [Research of Parameter Uncertainty for the HSPF Model Under Different Temporal
Scales].
AB - Various hydrological models have been applied to the management of water
resources and water quality. However, parameter uncertainty is of perpetual
interest in the application of hydrological models. In this context, the HSPF
model was constructed and calibrated using monthly observed stream data from 1998
to 2010 in the Chaohe River watershed, northeast of Beijing. Specifically, the
sensitivity and uncertainty of the model parameters were investigated by the GLUE
algorithm with the PEST platform. The major results were illustrated as follows:1
the hydrological simulation shows good performance with Nash-Sutcliffe efficiency
of 0.84 and 0.55 in the period of calibration and validation, respectively; 2 the
parameters were divided into three categories:global sensitive parameters (LZSN,
INFILT, IRC, and AGWRC), regional sensitive parameters (UZSN), and non-sensitive
parameters (DEEPFR, BASETP, AGWEPT, INTFW, and CEPSC); 3 strong correlations were
detected within the sensitive parameters, which further involved significant
negative correlations (LZSN~INFILT, INFILT~UZSN, and UZSN~AGWRC) and a positive
correlation (LZSN~UZSN) and (UZSN~AGWRC); 4 the equifinality for different
parameters was found in the HSPF model, indicating that parameter sets determine
the simulation performance rather than individual parameters; 5 among various
external factors, precipitation was identified as the most important condition
for simulation uncertainty; and 6 the temporal difference in simulation
performance was considered using annual, seasonal, and monthly scales with
simulation precisions of 81.80%, 78.70%, and 80.56%, implying that the annual
scale might be the optimal simulation period with higher accuracy. This research
result is useful for the application and localization of the HSPF model.
PMID- 29965503
TI - [Contribution of Nitrogen Sources in Water Sources by Combining Nitrogen and
Oxygen Isotopes and SIAR].
AB - It is very important to identify nitrate sources in reservoirs that serve as high
quality water sources to control its eutrophication. Stable isotopes (delta15 N
and delta18O) and a Bayesian model (stable isotope analysis in R, SIAR) were
applied to identify nitrate sources and estimate the proportional contributions
of multiple nitrate sources in four reservoirs (Qingshan reservoir, Duihekou
reservoir, Siling reservoir, and Lifan reservoir) that serve as sources of
drinking water in the Hangjiahu area, one of the most densely populated and most
quickly developing areas in East China. It was shown that nitrogen pollution,
which was dominated by nitrate (NO3-), existed in the four reservoirs. Greater
human activities caused more nitrogen pollution (average NO3- concentration 0.21
mmol .L-1) in the Qingshan reservoir. A significant positive correlation (P<0.01)
was observed between Cl- and NO3-. The analysis of the water in the Duihekou
reservoir, Siling reservoir, and Lifan reservoir, with lower Cl- concentrations
and higher NO3-/Cl- ratios, suggested that chemical fertilizer was the main
source, while the analysis of the water in the Qingshan reservoir, with medium Cl
concentrations and NO3-/Cl- ratios, indicated a mixture of NO3- sources. The
delta15 N ranged from 0.90/00 to 7.20/00, and the delta18O ranged from 2.80/00 to
14.10/00 in the four reservoirs. The delta18O values in more than 86% of the
water samples were less than 100/00, and the delta15 N/delta18O values in 93% of
the water samples were less than 1.3. It was identified that nitrification rather
than denitrification acted as the primary N cycling process in the four
reservoirs. SIAR was used to estimate the proportional contribution of five NO3-
sources (industrial wastewater, sewage/manure, chemical fertilizer, soil
nitrogen, and precipitation) in the Qingshan reservoir and of three NO3- sources
(chemical fertilizer, soil nitrogen, and precipitation) in the Duihekou
reservoir, Siling reservoir, and Lifan reservoir. The source apportionment
results showed that chemical fertilizers and soil nitrogen were the dominant
nitrate sources and their contributions were 75%-82%. It was revealed that
nitrogen pollution in the water source reservoir caused by cropping non-point
source pollution was very serious. Nitrate source contributions in Qingshan
reservoir also included sewage/manure (25%), soil nitrogen (7%), and
precipitation (6%), indicating that nitrogen pollution by sewage/manure should
not be ignored in the higher human activity areas. The nitrate source in the
Duihekou reservoir, Siling reservoir, and Lifan reservoir also included
precipitation, with the nitrate contribution from precipitation at 21%, 24%, and
15%, respectively. It was suggested that precipitation contributed more nitrate
to the water in areas with less human activity.
PMID- 29965504
TI - [Pollution Characteristics and Health Risk Assessment of Volatile Organic
Compounds in Baiyangdian Lake].
AB - In order to survey the present pollution from volatile organic compounds in
Baiyangdian Lake, 15 water samples were collected in March 2016, and analyzed for
54 VOCs by purge and trap gas chromatography-mass spectrometry. The distribution
characteristics and health risk assessments were investigated, and the pollution
from the VOCs was evaluated by a comprehensive pollution index. The survey showed
that:1 a total of 14 VOCs were detected in Baiyangdian water, with a 100%
detection rate for dichloromethane, benzene, toluene, ethylbenzene, xylene, and
1,3,5-trimethylbenzene; xylene had the highest concentration with an average
concentration of 564.9 ng .L-1; and trichloroethylene had the lowest
concentration with an average concentration of 3.3 ng .L-1 and a detection rate
of only 13.3%; 2 the total concentration of VOCs in Baiyangdian water was between
423.0 and 4207.8 ng .L-1, and benzene was the main pollutant, with its main
source coming from the effluent from the upstream sewage treatment plant, the
industrial wastewater, and the exhaust emissions of motor vehicles in the city;
and 3the health risk assessment showed that VOCs in Baiyangdian Lake did not
produce carcinogenic and non-carcinogenic risks to humans, and the VOC
comprehensive pollution index shows that the VOCs in the Baiyangdian Lake were at
a clean level.
PMID- 29965505
TI - [Fluorescent Characteristics and Environmental Significance of Particulate
Organic Matter in Lake Taihu, China].
AB - Thirty-two samples were collected from eight typical areas in Lake Taihu. Three
dimensional excitation-emission matrix fluorescence spectra (EEMs) and a parallel
factor analysis (PARAFAC) were applied to investigate the fluorescence
properties, the sources, and environmental significance of particulate organic
matter (POM) from the overlying water in Lake Taihu in summer. Differences in
fluorescence characteristics between POM and DOM (dissolved organic matter), and
that in POM between the grass lake and the algal lake were further examined.
There are five kinds of fluorophores in Lake Taihu:tyrosine-like fluorophores (C1
and C2), humic-like fluorophores (C3 and C4), and tryptophan-like fluorophores
(C5), among which significant correlations were found between C1 and C2, C3 and
C4, and C5 and two humic-like fluorophores (C4, C3). By comparing with the
fluorescence characteristics of DOM from earlier studies, it is found that there
are differences in compositions, sources, and correlations with water quality
between POM and DOM in Lake Taihu in summer. In summer, the contribution of
endogenous inputs to POM is greater than that of exogenous inputs in Lake Taihu
because the ranges in the fluorescence indices, FI, BIX, and HIX, are 1.78-2.35,
0.3-2.7, and 0.8-1.1, respectively. Significant correlations have been found
between humic-like fluorescent components and TN, TP, Chla, COD, POC, and SS,
suggesting that fluorescence analysis can be used as an important method for a
semi-quantitative analysis of nutrients. The protein-like components of the algal
lake mainly consist of tryptophan and tyrosine, while that of the grass lake
mainly contain tyrosine and a few tryptophan. It is worth noting that, the grass
lake contains more tyrosine relative to the algal lake (t test, P < 0.01).
Significant positive correlations between the protein-like and the humic-like
fluorescence are found in the algal lake, while it is not significant in the
grass lake. Significant positive correlations are found between the fluorescent
components (protein-like and humic-like) and chlorophyll-a in the algal lake,
while the correlation was only found between humic-like components and
chlorophyll-a in the grass lake.
PMID- 29965506
TI - [Distribution and Settlement of Microplastics in the Surface Sediment of Yangtze
Estuary].
AB - This study is designed to understand the microplastic contamination in the
coastal area of Yangtze estuary. The abundance and distribution profiles of
microplastics in the surface sediment of six sampling sites along the Yangtze
estuary were examined throughout one year. The detected average concentration of
microplastic, including fibers and fragments, in the surface sediment of Yangtze
estuary was (3.42+/-1.31) items .g-1 (DW). Sampling during four seasons, in the
months of January, April, July, and November, indicated that the highest
abundance of microplastics in Yangtze estuary surface sediment occurred in
January. A re-suspension experiment showed that microplastics tend to settle in
the surface sediment after re-suspension. The distribution and settlement of
microplastics along the coastal area has a high concordance with the dynamic
erosion-accretion process of the Yangtze estuary. Microplastics tend to settle in
accretion sites rather than in erosion sites.
PMID- 29965507
TI - [Water Chemistry and Characteristics of Dissolved Organic Carbon During the Wet
Season in Wulixia Reservoir, SW China].
AB - In recent years, scientists have focused on the karst carbon cycle. To better
understand the hydrochemical characteristics and the physical-chemical properties
of DOC in the wet season in karst areas, the water chemistry and DOC distribution
characteristics in Wulixia reservoir were analyzed. The molecular weight of the
water organic matter was analyzed based on the UV absorption spectrum. The
results showed that the water chemistry of Wulixia reservoir was HCO3-Ca .Mg, the
nutrient status of the water body was of the medium nutrient type, and the water
maintained a good quality. The DOC mass concentration was lower in the wet season
than in the dry season, and DOC was the main component of TOC. The DOC mass
concentration tended to decrease from the surface to the bottom in a vertical
direction. Chl-a and DIC were the main factors affecting the DOC vertical
distribution. The organic matter in the reservoir area related to the absorption
spectrum parameters of S275~295, M, SUVA254, and E253/E203 showed that the water
was dominated by constituents with small molecular weight, a high proportion of
fulvic acid, low proportion of humic acid, and weak aroma. The results showed
that the organic matter in the reservoir area was readily consumed by microbial
bioactivity and that it played an active role in the carbon cycle of the
reservoir. It also showed that the DOC endogenous characteristics of the
reservoir were strong and provided a sufficient carbon source for heterotrophic
microbes.
PMID- 29965508
TI - [Bioavailability of Dissolved Organic Carbon in Rivers for Typical Vegetation
Types in the Permafrost Regions on the Qinghai-Tibet Plateau].
AB - Samples collected from 12 rivers with typical vegetation types in the permafrost
regions on the Qinghai-Tibetan Plateau were incubated in the laboratory, and the
relationships among the vegetation types, river discharges, the compositions of
dissolved organic carbon (DOC), permafrost areas, riverine DOC concentration,
biodegradability of dissolved organic carbon (BDOC), and the biodegradation
kinetics were examined. The results showed that the DOC concentrations of typical
vegetation types in the basin, such as alpine meadow (AM), alpine swamp meadow
alpine meadow (ASM-AM), alpine meadow-alpine steppe (AM-AS), and alpine meadow
alpine steppe-bare soil (AM-AS-BL), were (5.17+/-0.21), (5.02+/-0.50), (3.55+/
0.25), and (2.79+/-0.41) mg .L-1, respectively. The values for the
bioavailability of river DOC of different vegetation types were (23.54+/-2.62)%,
(23.66+/-3.31)%, (18.17+/-5.26)%, and (11.72+/-15.56)%, respectively.
Correspondingly, the riverine DOC aromaticity increased along with the vegetation
cover, while the biodegradation and degradation rates decreased gradually. During
the incubation, the reaction of BDOC was in accordance with the first-order
kinetics equation. Furthermore, the BDOC in continuous permafrost regions of the
rivers was greater than that in the non-continuous permafrost regions. The BDOC
in higher discharges were lower than those with lower discharges. Taken together,
the results suggested that the vegetation types were the main controlling factors
for the BDOC, and BDOC was also related to the discharge and permafrost.
PMID- 29965509
TI - [Characteristics of Dissolved Organic Matter (DOM) and Relationship with
Dissolved Heavy Metals in a Peri-urban and an Urban River].
AB - Dissolved organic matter (DOM) is ubiquitous in the aquatic environment, playing
an important role in the fate of heavy metals in aquatic systems. In this study,
we characterized the DOM and heavy metals and their distribution in a peri-urban
river and an urban river in Ningbo city. In addition, the relationship between
DOM and dissolved heavy metals was also determined. Results showed that higher
DOC, CDOM, and FDOM concentrations were found in the river with the higher
urbanization level. Four fluorescence peaks were identified in the excitation
emission matrix (EEM) of DOM, including fulvic acid-like fluorescence peaks A and
C and protein-like fluorescence peaks B and T. The higher fluorescence
intensities of peak B and T were found in the urban river, and similar trends
were also found for the degree of humification and aromaticity of DOM. Similarly,
concentrations of heavy metals, such as As, Cu, and Mn, were significantly higher
in the urban river. Moreover, DOM had significant positive correlations with Cu,
Cr, Mn, As, Zn, and Pb in the urban river, while DOM only exhibited significant
positive correlations with Mn, Pb, and Cu in the peri-urban river. In conclusion,
urbanization level influenced the characteristics and concentrations of CDOM in
rivers which were closely related to the distribution of heavy metals.
PMID- 29965510
TI - [Migration and Transformation of Dissolved Organic Matter in Karst Water Systems
and an Analysis of Their Influencing Factors].
AB - Fluorescent substances are used as good tracers in dissolved organic matter (DOM)
to identify the source of DOM and its geochemical behavior in a hydrological
system. However, there are few studies on the karst aquifer system. Many
parameters in karst systems affect the DOM spectral information. A typical karst
watershed in Northern China was selected in this research. Excitation-emission
matrices (EEMs), parallel factor analysis (PARAFAC), and hydrochemical data were
applied to reveal the relationship between the composition and transformation of
DOM fluorescent substances in different karst water-bearing spaces. The source of
DOM and the effect of water chemistry on DOM transfer were also discussed. The
results showed that DOM in exogenous surface water and karst surface water in the
Yufu River watershed were mainly composed of tryptophan-like substances, while
the DOM in shallow karst water and deep karst water consisted of tryptophan-like
and tyrosine-like substances. A comprehensive analysis by fluorescence index
(FI), biological index (BIX), and humification index (HIX) displayed that the DOM
in shallow and deep karst water resulted from microbial decomposition. In
contrast, the DOM in karst surface water and exogenous surface water resulted
from land-based input and endogenous microbial decomposition, in which endogenous
contributions occupy a large proportion. Due to the chemical parameters of karst
water, these three kinds of fluorescent substances extracted by PARAFAC had
obviously different characteristics, i.e., 1 the tyrosine-like substances had a
strong adaptability to Ca2+ and HCO3-, and the proportion of the tyrosine in
karst water was relatively large; 2 the tryptophan substance followed an opposite
trend; and 3 there was a significant positive correlation between fulvic acid and
TDS, turbidity, Cl-, and SO42-. Observations of the watershed runoff revealed
that the DOM in shallow karst water in the upper reaches came mainly from the
soil and microbial degradation. The organic matter underwent a large amount of
microbial decomposition and exogenous input when the water was rejuvenated with
springs. After infiltration to the deep karst water in the lower reaches, the DOM
gradually were converted to low aromatic hydrocarbon organic compounds and
decreased macromolecules of DOM. Subsequently, the fluorescence intensity was
weakened. The principal component analysis (PCA) extracted three principal
components. They were the water mineralization index, soil leaching index, and
hydrochemical/biochemical process index. The water mineralization index consists
of hydrochemical parameters reflecting the water infiltration, transformation,
and flow conditions in the karst system. The soil leaching index contains TOC,
NO3-, and protein-like indicators relating to the relationship between protein
like substances and soil and natural leaching. The hydrochemical/biochemical
process index is composed of Ca2+, HCO3-, FI, and fulvic acid indicators that
illustrate the water chemistry and biochemical processes in the karst water
system. In addition, the study also showed that total fluorescence intensity,
fulvate-like substances, and protein-like substances can be used as a tracer for
rapid seepage, transformation, and aquifer fragility for karst water,
respectively. The results of the study are important in understanding the
biogeochemical cycle of DOM in the karst water system and also helpful for
controlling organic pollution. It also provides a new tool for characterizing the
geochemical processes of organic matter in karst system.
PMID- 29965511
TI - [Source and Distribution of Dissolved Metal Ions in the Backwater Area of Pengxi
River in Three Gorges Reservoir].
AB - This study uses the Gaoyang Lake section of the Pengxi River, the largest
tributary on the northern bank of the Three Gorges Reservoir (TGR), as an example
for exploring the distributions and dynamics of Ca, Zn, Fe, Cr, Pb, Cu, and Hg
ions in the tributaries of TGR where the water level fluctuates due to dam
regulation. Samples were taken 21 times, once every 17.3 days, at four sampling
sites in Gaoyang Lake, which is in a perennial backwater zone of the Pengxi
River, during one year from June 5, 2013 to May 29, 2014. At each sampling site,
water samples were taken from the surface layer (0-0.5 m), middle layer, and
bottom layer (0.5 m above the bed mud). During winter when the water was not
stratified, the middle layer samples were taken at 1/2 depth, and when water was
stratified in other seasons, the middle layer samples were taken from the thermal
layer. Inductively coupled plasma atomic emission spectrometry (ICP-AES) and cold
vapor atomic absorption methods were adopted to determine the concentrations of
the metals. Excel and SPSS were used for data analysis and Matlab for building 3
D prisms displaying concentration distributions of Hg ions in the high water
level period (175 m, November-April in the ensuing year), sluicing period (May
middle June), low water level in the flooding season (145 m, June-August), and
the storage period (September-November). The results provided the following
observations 1 Concentrations of Cr, Pb, Cu, Zn, and Hg ions were lower than
those in Class III of the water environment quality standard (GB 3838-2002). 2
Cr, Pb, and Cu had high peak values during the storage and sluicing period, and
the lowest values during the high water level period. Cr, Pb, and Cu were derived
from the main stream of Yangtze, while Fe and Zn were from the Pengxi River
locally. The concentration of Hg ions was affected by both the main stream and
endogenous sources. As the water column stratified, metal ions did not mix among
the stratified layers in Gaoyang Lake. 3 The conductivity was significantly lower
during the high water level period than during other water level periods. The
main material that affects the conductivity of Gaoyang Lake could be nonmetallic
ions.
PMID- 29965512
TI - [Differences in Diffusive Fluxes of Nutrients from Sediment Between the Natural
River Areas and Reservoirs in the Lancang River Basin].
AB - A field survey was carried out to investigate the diffusive fluxes of nitrogen
and phosphorus from sediment in the natural river areas and cascaded reservoirs
in the Lancang River Basin from February through March in 2017. In the natural
river areas, the mean value of total nitrogen (TN) concentrations in the sediment
pore water was about 15.254 mg .L-1, and the total phosphorus (TP) was only 0.654
mg .L-1; while in the reservoirs, the mean value of TN and TP were 6.577 mg .L-1
and 1.432 mg .L-1, respectively. Both nutrients in the overlying water were less
than that in the sediment pore water. The mean diffusive flux of total dissolved
nitrogen (DTN) was almost 2.117 mg .(m2 .d)-1 in the natural river areas, and the
mean value of total dissolved phosphorus (DTP) was 0.044 mg .(m2 .d)-1, while the
mean value of DTN and DTP were 0.785 mg .(m2 .d)-1 and 0.053 mg .(m2 .d)-1 in the
reservoirs, respectively. The TN content reaches the maximum in the overlying
water-interstitial water vertical surface sediments. It was concluded that
cascaded hydropower had greatly changed the nutrient exchange between the
sediment and overlying water. Different hydrodynamics and varied chemical
environments in the sediment could be additional causes.
PMID- 29965513
TI - [Nutrient Distribution Characteristics of the Sediment-water System in the
Xiangxi River During the Impoundment of TGR].
AB - This study characterizes the nutrient distribution of the sediment-water system
in the Xiangxi River (XXR) during the impoundment of the Three Gorges Reservoir
(TGR). In 2016, the research group obtained samples in the Xiangxi River,
analyzed the distribution of nitrogen, phosphorus, and O.M. (organic matter) in
the sediment-water system, explored the characteristics of "source-sink" between
the interstitial water and overlying water, and carried out a cluster analysis
for the sampling sites. The results showed that rho(TN) in the sediments was
higher than in the estuary, and the rho(TN) was close to that in the middle and
downstream samples of the river. The rho(TP) in the upstream sample was the
highest of all sites, rho(O.M.) presented low distribution characteristics in the
downstream, and the maximum value of rho(O.M.) exceeded the critical point (1.5%)
within a depth of 10 cm, and there was a certain risk of release. For the
distribution in the overlying water, rho(DTN) and rho(DTP) were the largest in
the estuary, rho(DTN) decreased from the estuary to the upstream, and rho(DTP)
did not change along the river. During the study, DTN, NH4+-N, and DTP in all
sites (except CJ point) were released as nutrients to the overlaying water as the
"source," but some points for NO3--N and PO43--P presented as "sources," and some
of them presented as "sinks." The "source-sink" process of nitrogen was stronger
than that of phosphorus. This was due to the difference between the oxidation
environment at the bottom of the XXR and the stream flow backward depth of the
Xiangxi bay during impoundment. Based on the results of a cluster analysis, the
characteristics of CJ, 1, and 2 indicated similar sediment-water systems, while
the characteristics of 3 and 4 were similar.
PMID- 29965514
TI - [Effects of Submerged Macrophytes on Different Phosphorus Fractions in Overlying
Water and Interstitial Water].
AB - The effects of Myriophyllum spicatum L. with developed root systems and rootless
Ceratophyllum demersum on the concentration and proportion of different
phosphorus fractions in the overlying water and the interstitial water were
investigated by batch simulation experiments. The effects of different types of
submerged macrophytes on the phosphorus fraction in the overlying water and
interstitial water were explored. The results indicated a significant influence
on the concentration of dissolved phosphorus in the overlying water and
interstitial water by the growth of Myriophyllum spicatum L. and Ceratophyllum
demersum. 1 The absorptivities of DTP, SRP, and DOP by Myriophyllum spicatum L.
in the overlying water were 7.0%, 11.7%, and 3.5%, respectively, and in the
interstitial water were 20.8%, 12.5%, and 48.4%, respectively. 2 The
absorptivities of DTP, SRP, and DOP by Ceratophyllum demersum in the overlying
water were 30.3%, 54.9%, and 13.2%, respectively, and in the interstitial water
were 19.3%, 3.8%, and 30.4%, respectively. 3 The content of SRP in Myriophyllum
spicatum L. group, Ceratophyllum demersum group, and the control group decreased
13.0%, 34.0%, and -0.9%, respectively; the PP increased 18.2%, 33.1%, and 4.2%,
respectively; and the DOP increased 7.2%, 17.68%, and -4.35%, respectively. The
results provide reference for eutrophic lake ecologic restoration.
PMID- 29965516
TI - [Distribution of Phosphorus Fractions in Surface Sediments of Minjiang
Mainstreams].
AB - In recent years, the total phosphorus pollution in Minjiang River was serious,
and the surface sediments of the Minjiang River also threatened water quality. To
study the spatial distributions of phosphorus in the surface sediments of the
Minjiang River, samples of surface sediments were collected upstream (Aba
District) and downstream (Yibin District) of the Minjiang River in December,
2016. The sediments were analyzed with the modified sequential extraction method
(SEDEX) to obtain six forms of phosphorus, including exchangeable phosphorus (Ex
P), exchangeable organic phosphorus (Org-P), iron-bound phosphorus (Fe-P),
authigenic phosphorus (Ca-P), detrital phosphorus (De-P), and refractory
phosphorus (Res-P). The results indicated that the contents of total phosphorus
(TP) in surface sediments ranged from 522.17 MUg .g-1 to 979.22 MUg .g-1, which
were far more than the soil phosphorus background values (700 MUg .g-1). The
spatial distribution characteristics of the TP of surface sediments indicated
that the TP concentrations in sediments at the Meishan sections (the middle reach
of the Minjiang River) were higher than those in the other sections. This was
related to the smaller particle size and higher OM contents in sediments in the
Meishan sections. The main phosphorus forms in the sediments in the Minjiang
River were Ca-P and De-P, with their concentrations accounting for 75% of TP in
the sediments. The bio-available phosphorus, which included Ex-P, Org-P, and Fe
P, accounted for 0.31%-29.62% of TP in the sediments of the Minjiang River. The
concentrations of bio-available phosphorus in sediments at the Meishan sections
and Leshan sections (the middle reach) were highest, indicating that bio
available phosphorus in the surface sediments was high, and its potential
environmental impact risks were higher.
PMID- 29965515
TI - [Distribution Characteristics and Fluxes of Nitrogen and Phosphorus at the
Sediment-water Interface of Yuqiao Reservoir].
AB - Yuqiao Reservoir is an important source of drinking water in Tianjin. In recent
years, the eutrophication status is becoming more and more serious, but its
internal loading and distribution characteristics of nitrogen and phosphorus is
not clear. The profiles of nitrogen and phosphorus at the sediment-water
interface were analyzed using the Peeper (pore water equilibrium) technique and
the spatial distribution was investigated. The existing forms of the released
nitrogen and phosphorus were investigated by the static intact sediment cores,
and the fluxes of nitrogen and phosphorus at the sediment-water interface were
estimated by static incubations with intact sediment cores. The results
demonstrated the following. 1 The contents of PO43--P, NH4+-N, NO3--N, and NO2--N
in sediments were 0.5-6.5, 0.5-10.9, 2.2-16.2, and 0.05-0.6 mg .kg-1,
respectively. The contents of nutrient were lower as depth increased, and
horizontal distribution characteristics indicated significant differences. 2 The
contents of PO43--P and NH4+-N in the interstitial water were much higher than in
the overlying water, suggesting that the interstitial water had the potential to
diffuse nutrients to the overlying water. The concentrations of PO43--P and NH4+
N in the interstitial water increased rapidly at 0-5 cm and then decreased
gradually. 3 PO43--P and NH4+-N diffused from the sediment to the overlying
water, and the fluxes of them were 1.1-13.3 mg .(m2 .d)-1 and 20.6-250.5 mg .(m2
.d)-1, respectively. The exchange fluxes of NO3--N and NO2--N ranged from -20.4
to 33.4 mg .(m2 .d)-1 and from -7.4 to 0.4 mg .(m2 .d)-1, respectively. PO43--P
and NH4+-N were the main nutrients in the sediment released to the overlying
water. The fluxes were high in the south and low in the north, and also high in
the mouth of the Linhe River and downstream of the reservoir. Compared with
similar studies, the fluxes at the sediment-water interface of Yuqiao Reservoir
were relatively high, indicating that the sediment was an important source of
nutrients for the overlying water in Yuqiao Reservoir.
PMID- 29965517
TI - [Nitrate Uptake Kinetics and Correlation Analysis in an Agricultural Drainage
Ditch].
AB - To investigate the whole-reach nitrate (NO3--N) uptake dynamics in a headwater
agricultural stream, we performed five pulse tracer additions of a reactive
solute (as KNO3) and a conservative solute (as NaBr) in an agricultural drainage
ditch in Hefei district, Chaohu Lake basin, from October 2016 to April 2017. The
TASCC (tracer additions for spiraling curve characterization) approach and
Michaelis-Menten (M-M) method were applied for the simulation of NO3--N uptake
dynamics. Results showed that the ambient areal rate of total NO3--N uptake Uamb
varied from 11.40 to 69.13 MUg .(m2 .s)-1 with an average of 34.45 MUg .(m2 .s)
1, and the ambient uptake velocity Vf-amb averaged 0.24 mm .s-1 and varied from
0.07 to 0.43 mm .s-1 across three well-mixed sub-reaches in the study. The
ambient uptake length Sw-amb averaged 199.06 m with a range from 92.51 to 405.74
m, which was much smaller than the length of the drainage ditch (about 2.5 km),
suggesting that the agricultural drainage ditch had a high potential for NO3--N
retention. Generally, the M-M model fit the NO3--N uptake dynamics well, and the
maximum uptake Umax ranged from 158 to 1280 MUg .(m2 .s)-1 with a mean of 631.13
MUg .(m2 .s)-1. The half saturation constant Km ranged from 0.16 to 5.52 mg .L-1
with a mean of 1.46 mg .L-1. According to correlation analysis, Sw-amb was
negatively correlated with NO3--Namb, and Uambwas significantly positively
correlated with NO3--Namb, while other nutrient spiraling metrics were not
correlated with the NO3--N ambient concentration. Hydrological conditions had no
distinct effect on the NO3--N retention, but both the width variability Fw and
variability in cross-sectional area FA were significantly correlated with most of
the nutrient spiraling metrics, indicating that geomorphic features in the
drainage ditch evidently impacted NO3--N uptake.
PMID- 29965518
TI - [Influencing Factors for Phosphorus Removal by Modified Bio-ceramic Substrates
Coated with ZnAl-LDHs Synthesized by Different Modification Conditions].
AB - Under different pH conditions, the hydrothermal and co-precipitation method was
used to synthesize layered double hydroxides (LDHs) coated on bio-ceramic
substrates with three different Zn2+/Al3+ molar ratios. Applying the original and
six kinds of modified bio-ceramic substrates coated with ZnAl-LDHs (bio
ceramic/ZnAl-LDHs) in simulated vertical-flow constructed wetlands, experiments
for phosphorus removal and isothermal adsorption were conducted to analyze the
mechanism and effect of each synthesis factor. The results showed that ZnAl-LDHs
(pH=11) had a more obvious effect on phosphorus removal, especially for bio
ceramic/ZnAl-LDHs (pH=11, 1:1), whose average removal rates of TP, TDP and SRP
were enhanced over 70%. Its maximum adsorption capacity for phosphorus was three
times higher than that of the original bio-ceramic. Both pH and Zn2+/Al3+ molar
ratio affected the configuration and coating properties of bio-ceramic/ZnAl-LDHs
at the time of synthesis, and pH was the main synthesis factor for phosphorus
removal efficiency of bio-ceramic/ZnAl-LDHs. Through reasonable regulation of pH
and Zn2+/Al3+ molar ratio when bio-ceramic/ZnAl-LDHs was synthesized, the
phosphorus removal efficiency could be improved effectively.
PMID- 29965519
TI - [Removal of Odorants in Drinking Water Using VUV/Persulfate].
AB - In order to solve the odor problem of drinking water, the performance of a
VUV/persulfate process and its influencing factors were investigated
systematically for removing odors from 2-MIB and GSM. The results showed that it
was difficult to remove 2-MIB and GSM using PS alone with a PS concentration of
0.5 mmol .L-1, but the removal rates of 2-MIB and GSM by the VUV/PS process could
be increased by 76% and 74%, respectively, compared with VUV alone. The
performance of the VUV/PS process was mainly affected by the PS concentration and
VUV intensity. When the PS concentration increased from 0.25 to 2 mmol .L-1 and
the VUV intensity increased from 113.2 to 618.5 MUW .cm-2, the removal rate of 2
MIB was increased by 42% and 39%, respectively, and the removal rate of GSM was
increased by 34% and 16%, respectively. The effect of pH on 2-MIB and GSM removal
was not significant. The occurrence of HCO3- and humic acid will decrease the
removal rates of 2-MIB and GSM, and the degree of reduction increases with the
concentrations of HCO3- ion and humic acid. The VUV/PS process can effectively
degrade the typical odorants in water and can reduce the difficulty of subsequent
water treatment.
PMID- 29965520
TI - [Degradation of OG with Peroxymonosulfate Activated by a MnFe2O4-graphene
Hybrid].
AB - The rG-MnFe2O4 was synthesized by hydrothermal method and characterized by
transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier
transform infrared spectroscopy (FT-IR), and Raman spectra. The rG-MnFe2O4 was
used to activate peroxymonosulfate (PMS) to decolorize azo dyes, e.g., Orange G,
and the effect of PMS dosage, rG-MnFe2O4 loadings, initial pH, and the
concentration of Cl- were investigated. The results indicated that the
degradation rate of OG was 100% within 27 min with 0.3 g .L-1 of rG-MnFe2O4 and
at a 40:1 of PMS:OG molar ratio. The decolorization efficiency of OG increased
with increasing PMS concentration and increasing rG-MnFe2O4 dosage. The initial
pH had a significant effect on OG degradation, and pH 5.00 was most favorable for
its decolorization. In addition, the addition of Cl- accelerated the
decolorization of OG, and the decolorization rate increased with increasing
concentration of Cl-. The rG-MnFe2O4 also exhibited an excellent reusability, and
its activation of PMS was still observed after five rounds of tests. From the
analysis of UV-vis spectra and gas chromatography-mass spectrometry (GC/MS), the
naphthalene ring and azo band were found to be destroyed, with p-nitrophenol and
phthalic acid as the main degradation products. Finally, a TOC analysis indicated
that a certain degree of OG mineralization was obtained in the rG-MnFe2O4/PMS
system.
PMID- 29965521
TI - [Mechanism of As(V)Removal from Water by Lanthanum and Cerium Modified Biochars].
AB - Loaded lanthanum or cerium biochars were prepared by one step pyrolysis of La
(NO3)3-laden or Ce (NO3)3-laden rice hulls and were employed for enhancing the
adsorption of As (V) from water. In contrast with BC and Ce-BC in this study, La
BC had better adsorption capacity in the acidic condition. The maximum adsorption
capacity could reach 20.1 mg .g-1. With increased pH, the adsorption capacity of
La-BC was reduced. The highest adsorption capacity reached 39.1 mg .g-1 (pH=5)
and the lowest was 17.6 mg .g-1 (pH=9). The resulting La-BC with As (V)
adsorption was characterized by SEM-EDS, FTIR, and XPS. There were two types of
active adsorption sites for As (V), oxygen-rich functional groups and lanthanum
oxide. Although Ce-BC had oxygen-rich functional groups and cerium oxide, it was
unable to participate in the adsorption of As (V) from water.
PMID- 29965522
TI - [Adsorption of Dissolved Organic Matter with Different Relative Molecular Masses
on Inorganic Minerals and Its Influence on Carbamazepine Adsorption Behavior].
AB - In this work, sorption experiments were conducted to understand the adsorption
characteristics of dissolved organic matter (DOM) of different relative molecular
masses on minerals and the effects of their interaction with PPCPs on the
adsorption process. This study chose carbamazepine (CBZ) as the target pollutant,
quartz sand as the inorganic mineral, and commercial humic acid (HA) as the DOM.
We studied the structural characteristics of HA with different relative molecular
masses and the impact of their interaction with CBZ on their adsorption based on
dialysis experiments and infrared spectroscopy. It was found that large molecular
weight fractions of HA, which contain more hydroxyl, aromatic hydrocarbons, and
aliphatic hydrocarbons, were mainly hydrophobic substances, while the smaller
fractions, containing more alcohols and carboxyl groups, were mainly hydrophilic
substances. The combination of HA and CBZ had two major mechanisms, the
combination of amino groups of CBZ and polar functional groups in small molecular
weight fractions of HA and hydrophobic interactions between hydrophobic groups
and aliphatic or/aromatic compounds in large molecular weight HA. The interaction
between CBZ and HA resulted in obvious differences in the adsorption of HA or
CBZ. When CBZ does not exist, hydrophobic combinations occurred between HA
through the hydrophobic components and quartz sand, which also experienced the
exchange coordination reaction with the hydroxyl or carboxyl group of HA. In
addition, HA adsorbed the aliphatic and hydrophobic macromolecular components.
Quartz sand was used to adsorb the large hydrophobic molecules. When CBZ existed,
it adsorbed the small molecular weight fractions of HA. The maximum HA adsorption
capacity of quartz sand decreased. CBZ could be adsorbed on quartz sand by
hydrophobic interaction, van Edward forces, and polarity interactions in the
absence of HA. When adding HA, the adsorption increment of carbamazepine on
quartz sand was due to the co-adsorption or accumulation of HA and CBZ after
their combination.
PMID- 29965524
TI - [Enhanced Coagulation as a Pretreatment for Low Temperature Wastewater].
AB - The effects of low temperature on enhanced coagulation were studied. A new
composite coagulant called SynthA was synthesized. The effects of enhanced
coagulation on the removals of dissolved organic matter, dissolved organic
nitrogen, and so on under room temperature or low temperature (2-5C) were
determined, and their influences on biological treatments were investigated by
using membrane fractionation distribution, three-dimensional fluorescence
spectrum (3DEEM), and differential ultraviolent absorbance. The results showed
that, under room temperature, the removals of particulate COD, particulate
nitrogen, colloidal COD, and colloidal nitrogen were highly correlated with
turbidity reduction by coagulation using aluminum chloride (AlCl3), poly aluminum
chloride (PACl), and SynthA as coagulants separately, while the relationship was
not clear between the dissolved parameters and turbidity reduction. The reduction
of fluorescence value of dissolved organic matter after coagulation was much
higher than that of dissolved COD. Dissolved organic nitrogen (DON) is removed to
the greatest extent by preset coagulation along with particulate nitrogen (PN)
and colloidal nitrogen (CN). Low temperature affected enhanced coagulation in
many aspects. It inhibited turbidity reduction and COD removal by the three
coagulants with the order being AlCl3 > PACl > SynthA. It exhibited differential
influences on the removals of particulate, colloidal and dissolved COD, and
nitrogen, and it showed greater adverse effects on particulate and colloidal COD
and nitrogen. The fluorescence value of dissolved organic matter in low
temperature water showed a significant increase, and its reduction by coagulation
was high, compared with that in room temperature water. Low temperature
coagulation exerted greater impacts on ultraviolet differential absorbance than
did room temperature. Under low temperatures, slight increases of total nitrogen
(TN) removal, DN, and DON removals were achieved by using SynthA as coagulant,
and removals of PN and CN were maintained, compared with room temperature. As an
example, when SynthA dosage was above 30 mg .L-1, DON removal reached 28.5%-41.7%
at low temperature, while the removal was only 17%-31.4% at room temperature. A
large portion of the COD and some TN were removed by coagulation as a
pretreatment, indicating that a large amount of the time in an aeration pond
could be reduced, and the removal efficiency of TN would be stabilized.
Therefore, in winter, the decrease of biological treatment efficiency could be
alleviated to some extent by using enhanced coagulation with an adaptable
coagulant, such as SynthA as a pretreatment, which would relieve the stress of
denitrogen and stabilize treatment efficiency.
PMID- 29965523
TI - [Pollution Characteristics of Organophosphorus Flame Retardants in a Wastewater
Treatment Plant].
AB - Sewage water, the influent of the secondary sedimentation tanks, the final
effluent, sludge from biological pools, and dewatered excess sludge samples from
eight wastewater treatment plants (WWPTs) in Suzhou, including those from seven
A2/O processes and one oxidation ditch process, were collected in 2017 to study
the pollution characteristics of organophosphorus flame retardants (OPFRs) in
WWPTs. Accelerated solvent extraction (ASE) combined with a solid-phase
extraction method was used to detect the concentration of 10 organic phosphorus
flame retardant (OPFRs). The removal efficiency of OPFRs was compared and final
daily emissions were estimated. The results showed seven kinds of OPFRs were
detected in the influent, final effluent, and sludge. The total content of OPFRs
in the influent ranged from 0.74 to 222.65 MUg .L-1 (average 65.56 MUg .L-1),
while the content in the final effluent was between 0.46 and 175.41 MUg .L-1
(average 22.99 MUg .L-1). The concentration in the effluent of the secondary
sedimentation tank was between 0.48 and 178.14 MUg .L-1 (average 43.14 MUg .L-1).
The daily emission of OPFRs in final effluent was 36.69-2177.12 g .d-1. The
content in the dewatered excess sludge was between 89.32 and 596.24 MUg .g-1 dw
(average 249.35 MUg .g-1 dw), the minimum daily emission was 3.57-7.15 kg .d-1,
and the maximum was 47.70-95.40 kg .d-1. The oxidation ditch process has a good
removal rate of OPFRs, at 92%, while the A2/O process removal rate covered a
large range from 11%-99%. Three chlorinated OPFRs, TCEP, TCPP, and TDCPP, were
the main components in the influent and final effluent, mainly because of the
large consumption of OPFRs and also because the removal rate by the traditional
wastewater treatment technology was low.
PMID- 29965525
TI - [Operating Characteristics and Fouling Characteristics of a RO Membrane System
for Desalination of Dyeing Wastewater].
AB - The reverse osmosis (RO) process is of great significance for the desalination
and reclamation of dyeing wastewater. However, fouling of RO membranes has been a
severe problem and key limiting factor in the widespread application of the RO
process. The operating characteristics and fouling characteristics of a RO
membrane system for desalination of dyeing wastewater were investigated in an
industrial park in Guangdong Province. The results showed that the COD and
turbidity of RO influent after ozone oxidation-sand filtration-ultrafiltration
(UF) processes were 12.4 mg .L-1 and<1 NTU, respectively, with a stable
desalination rate of the RO system of around 98%. The COD and turbidity of the RO
effluent were 0.7 mg .L-1 and 0.12 NTU, respectively. However, after 3 years of
operation, the pressure drop across the membrane reached 0.6 MPa, and the
permeate flux decreased to 120 m3 .h-1, which could not be restored to its
original flux by chemical cleaning. The organic and inorganic matter occupied
(53.5+/-0.2)% and (46.5+/-0.2)% of the deposits on the RO membrane, respectively,
suggesting both organic and inorganic fouling were the main problems for the RO
membrane. Si, Al, and Ca were major inorganic elements on the RO membrane. Large
amounts of Si, Al, and organic matter deposited on the RO membrane were dissolved
easily by alkaline (NaOH) solution than acid (HCl) solution.
PMID- 29965526
TI - [Optimization of the Nitrogen Removal Performance on the CANON Process in a
Biofilm Reactor: From FBBR to MBBR].
AB - To optimize the performance of completely autotrophic nitrogen removal over
nitrite (CANON), a CANON process with modified polyethylene as carriers was
operated in a moving-bed biofilm reactor (MBBR), using synthetic inorganic
ammonia-rich wastewater (NH4+-N about 400 mg .L-1) as influent at 30C+/-1C. With
an HRT of 6 h, pH at 7.8, and filling rate of 35%, the average removal rate of
NH4+-N and TN reached 74.28% and 87.93%, respectively, and the highest removals
reached 84.68% and 98.82%, respectively, while the value of DeltaNO3-/DeltaTN was
0.12, which was close to the theoretical value of 0.127. This suggested that
CANON sludge gradually adapted to the environment in the MBBR and began to enter
the stable stage. Compared with a fixed-bed biofilm reactor (FBBR) under the same
influent and operating conditions, the mean square error of MBBR and FBBR in
terms of NH4+-N removal rate, TN removal rate, and TN removal load were 8.31% and
14.06%, 7.09% and 1.79%, 0.17 kg .(m3 .d)-1 and 0.27 kg .(m3 .d)-1, respectively,
the former are lower than the latter. Moreover, while DO concentrations of MBBR
and FBBR were 1.96 mg.L-1 and 3.09 mg .L-1, respectively, their TN removals of
per liter carriers were 0.53 kg .(m3 .d)-1 and 0.37 kg .(m3 .d)-1. Therefore, it
was concluded that:1 MBBR had a more stable nitrogen removal performance than did
of FBBR, and 2 MBBR had a higher TN removals of per liter carriers than did FBBR
in addition to the higher utilization rate of oxygen.
PMID- 29965527
TI - [Microbial Community Dynamics During Two Sludge Granulation Processes].
AB - Aerobic granular sludge (AGS) was cultivated in a sequencing batch reactor (SBR).
In this study, AGS was broken during the formation process and then mature AGS
formed again. The microbial community dynamics during two sludge granulation
processes were investigated using high-throughput sequencing to reveal the
dominant bacteria beneficial to AGS formation. The abundance dynamics of
nitrifying microorganisms were analyzed by a quantitative polymerase chain
reaction (qPCR). The results showed that the amount of extracellular protein and
polysaccharides increased during two sludge granulation processes. The abundance
of ammonia oxidizing archaea (AOA) increased during the first AGS formation
process and during the process of AGS maturation. The abundance of ammonia
oxidizing bacteria (AOB) decreased during the first AGS formation process, while
it maintained a higher abundance than AOA during AGS cultivation. Microbial
diversity decreased with AGS formation. The relative abundance of Proteobacteria
increased by 12.29% and 5.90% during two sludge granulation processes,
respectively. Candidatus Competibacter belonging to Proteobacteria was enriched
during two sludge granulation processes, accounting for 14.20% in mature AGS.
Overall, extracellular protein and polysaccharides may have contributed to the
sludge granulation. Both AOA and AOB might have been involved in ammonia
oxidation. This study indicated that Ca. Competibacter might contribute to AGS
formation.
PMID- 29965528
TI - [Sludge Conditioning Performance of Polyaluminum, Polyferric, and Titanium
Xerogel Coagulants].
AB - The sludge conditioning performance of inorganic Al, Fe, and Ti coagulants were
systematically compared in terms of specific resistance to filtration (SRF), the
content of protein and polysaccharide in extracellular polymeric substances
(EPS), the change in three-dimensional excitation emission matrix fluorescence
(3D-EEM), the molecular weight of organic matter in EPS, and the floc size and
surface morphology. The sludge conditioning ability and the mechanism were
systematically analyzed. The results showed that the sludge conditioning ability
of the three inorganic coagulants was in the order of polyaluminum chloride (PAC)
> titanium xerogel coagulant (TXC) > polymeric ferric sulfate (PFS). After
conditioning, the contents of protein and polysaccharide in the EPS were greatly
reduced, especially in the loosely bound EPS (LB-EPS). The combined capacity for
coagulation between TXC/PFS and organic matter was stronger than that of PAC. The
content of polysaccharide in LB-EPS was the key factor affecting the sludge
dewatering performance but not the coagulated floc size. The surface charge and
the chelating ability with organic matter co-determined the sludge dewatering
ability. The organic cationic polymer, polyacrylamide (PAM), made the sludge
aggregate via charge neutralization. However, the use of PAM alone was not a good
choice owing to the low dewatering ability and the loose sludge structure. The
results here are helpful for the selection of suitable coagulants for sludge
conditioning.
PMID- 29965530
TI - [Effect of Different Ratios of Anaerobic Time and Aeration Time on the Formation
of Partial Nitrification Granules].
AB - Flocculent sludge with good nitritation performance and MLSS and SVI values of
3500 mg .L-1 and 162 mL .g-1, respectively, was inoculated in the R1, R2, and R3
groups of the same SBR reactors at room temperature (22-28C). The effects of
different anaerobic time and aeration time ratios (1:2, 1:1, and 2:1) on the
formation of partial nitrification granular sludge were studied. The results
showed that granules in three reactors were successfully formed at 103 d, 82 d,
and 64 d. The nitrosation rate of R1, R2, and R3 were 86%, 98%, and 96%,
respectively, and SVI decreased to 89, 75, and 58 mL .g-1 and MLSS increased to
2314, 2781, and 2946 mg .L-1, respectively, at the 85 d. The larger ratio of
anaerobic time and aeration time was more conducive to sludge granulation, better
settling, and nitritation performance. When the anaerobic time and aeration time
ratio was 1:2, the nitritation performance of the sludge decreased since the NOB
could not be suppressed, and the settling performance of the sludge became better
and then worse. In addition, at the larger ratio of anaerobic time and aeration
time, there was more PN and PS from microbial secretion. The PN of R1, R2, and R3
was smaller at the end of the anaerobic phase compared to that of the aerobic
phase in the early stage of granular formation, but were reversed in the
stabilization stage. The PS of the anaerobic phase was larger than that of the
aerobic stage over the entire process.
PMID- 29965529
TI - [Effects of Heat and Heat-alkaline Treatments on Disintegration and Dissolved
Organic Matter in Sludge].
AB - The hydrolysis of sludge organic matter is the rate-limiting step of anaerobic
sludge digestion. Because pretreatments can effectively convert the solid organic
matter into dissolved organic matter, it can improve the degradation rate and
methane conversion rate of organic matter. In this study, the effects of heat and
heat-alkaline treatments (two common pretreatments) on the composition, relative
molecular weight distribution, and structure of dissolved organic matter in
sludge were studied. The results showed that the heat and heat-alkaline
treatments released a large amount of organic matter, which resulted in the SCOD
increasing 21.9 times (heat treatment) and 47.8 times (heat-alkaline treatment).
These pretreatments changed the molecular weight distribution of dissolved
organic matter and decreased the molecular weight of the organic matter to the
greatest degree. The results of three-dimensional fluorescence spectroscopy
showed that both of the pretreatments can hydrolyze protein, the main component
of sludge soluble organic matter, with the heat-alkaline treatment being more
significant. In dissolved organic matter, the byproducts of the microorganisms
and humic acids are not easily hydrolyzed further by the two pretreatments. In
addition, the two pretreatments led to the appearance of new organic structures
and the change and even disappearance of the original organic matter.
PMID- 29965531
TI - [Spatial and Temporal Variation of Mercury in Municipal Sewage Sludge in China].
AB - In order to determine the occurrence of mercury (Hg) in the dewatered sewage
sludge (SS) from municipal wastewater treatment plants (MWTPs) in China, 315 SS
samples were collected from 40 MWTPs. The total Hg (THg) contents of the sludge
samples were analyzed using a DMA-80 Hg analyzer. It was found that THg in the
samples ranged from 0.45-15.42 mg .kg-1. The THg data followed a log-normal
distribution with a geometric mean of (2.19+/-3.16) mg .kg-1. THg contents in all
the sludge samples meet the criteria set for disposal (by co-landfilling) of
MWTPs sludge (GB/T 23485-2009). In terms of THg contents, 97.8% of the sludge was
suitable for land application in neutral and alkaline soils, while 86.7% of the
sludge was suitable for land application in acidic soil. THg in SS varied
greatly, not only among cities (variation coefficient of 105%), but also in the
same MWTP (variation coefficient of 0.6%-53.6% over seven days). Mercury contents
in SS of China showed a descending trend of North > Northeast > Northwest >
Southwest > East > Central > South China. Using the corresponding urban soil
background values of THg as references, Hg pollution levels of SS were evaluated
using the geological cumulative index method. It was found that SS from more than
60% of the cities sampled were heavily polluted by Hg. Mercury contents in the SS
of China showed a temporal trend of increasing then decreasing, with 2000-2009
being the peak period. Results of the present study provide significant data
support for the prevention and control of mercury pollution in sewage and SS in
China.
PMID- 29965532
TI - [Characteristics of N2O Release and Influencing Factors in Grass-type and Algae
type Zones of Taihu Lake During Summer].
AB - Spatial heterogeneity of N2O generation and emissions in multi-ecotype lakes
limited the accurate estimation of the N2O fluxes in lakes, but few studies on
the characteristics of N2O generation and emissions have been conducted. In this
study, N2O flux at the water-gas interface, dissolved N2O concentration in the
water column, and N2O flux at the sediment-water interface in typical grass-type
and algal-type zones of Taihu Lake were analyzed during summer, and indoor micro
environment experiments were conducted to illustrate the main factors affecting
the generation and emissions of N2O. The results showed that the N2O fluxes at
the water-gas interface, dissolved N2O concentration, and N2O fluxes at the
sediment-water interface of the emergent macrophyte type area was higher than the
algae-type area and submerged macrophyte area during the summer., with N2O fluxes
at the water-gas interface of (115.807+/-7.583), (79.768+/-1.842), and (3.685+/
0.295) MUmol .(m2 .h)-1, respectively. The dissolved N2O concentration in the
water column were (0.051+/-0), (0.029+/-0.001), and (0.018+/-0) MUmol .L-1,
respectively; and the N2O fluxes at the sediment-water interface were (178.275+/
3.666), (160.685+/-0.642), and (75.665+/-1.016) MUmol .(m2 .h)-1, respectively.
The spatial difference could be attributed to dominant plants and the
concentration of inorganic nitrogen in the water column. The results of micro
environment experiments showed that nitrate and organic carbon sources could
significantly increase the N2O production potential of sediments, the high
concentration of NH4+-N in the water column might inhibit the N2O production in
sediments, and the production rates of N2O in the sediment increased remarkably
when the incubation temperature increased, suggesting that the generation and
emissions of N2O were mainly restricted by nitrate, organic carbon, and
temperature in summer.
PMID- 29965533
TI - [Analysis of Greenhouse Gas Emission Characteristics and Their Influencing
Factors in the Algae Zone of Lake Taihu].
AB - In order to identify CH4 and CO2 emission flux characteristics and their impact
factors in the algal lake zone of Lake Taihu, CH4 and CO2 fluxes were observed by
the improved closed chamber method in Meiliang Bay in Lake Taihu. The
relationships between CH4 and CO2 flux and meteorological factors were analyzed.
The results showed that CH4 and CO2 fluxes had obvious diurnal variations. The
CH4 flux in the daytime was higher than that in the nighttime in spring; however,
the CH4 flux in the nighttime was higher than that in the daytime in summer. The
CO2 uptake flux in the daytime was higher than that in the nighttime in spring
and summer. The algae zone of Lake Taihu was a CH4 source for the atmosphere. The
average CH4 flux was 4.047 nmol .(m2 .s)-1 and 40.779 nmol .(m2 .s)-1 in spring
and summer, respectively. The zone was the CO2 sink for the atmosphere in spring
and summer. The average CO2 flux was -0.160 MUmol .(m2 .s)-1 and -0.033 MUmol
.(m2 .s)-1 in spring and summer, respectively. On an hourly scale, the CH4
emission flux was positively correlated with air temperature and water
temperature (r=0.20, P<0.01 and r=0.34, P<0.01, respectively). When wind speed
was lower than 6 m .s-1, the CH4 flux was positively correlated with wind speed
(r=0.71, P<0.01). The CO2 uptake flux had a significant positive correlation with
air temperature and wind speed (r=0.14, P<0.01 and r=0.33, P<0.05, respectively).
However, the CO2 uptake flux was negatively correlated with air pressure and
solar radiation (r=-0.41, P<0.01 and r=-0.35, P<0.01, respectively). The CO2
efflux had a significant positive correlation with wind speed (r=0.40, P<0.05).
The CO2 efflux was negatively correlated with solar radiation (r=-0.35, P<0.01).
On a daily scale, the CH4 emission flux had a significant positive correlation
with air temperature and water temperature (r=0.83, P<0.01 and r=0.78, P<0.01,
respectively).
PMID- 29965534
TI - [Dynamics of CO2 and N2O in Seasonal Frozen Soil Profiles for a Typical Steppe in
Inner Mongolia].
AB - In order to evaluate the effect of grazing on the mechanism for greenhouse gas
emissions in the seasonal frozen soils for a typical steppe in Inner Mongolia,
variations of N2O and CO2 concentrations in different soil layers were monitored
by an in situ gas collection system. Three conditions were selected:ungrazed
since 1979 (UG79), ungrazed since 1999 (UG99), and continuously grazed (CG). The
results showed that the profile soil N2O and CO2 concentrations demonstrated a
significant spatio-temporal distribution. 1 The average concentrations of CO2 in
the soil profile of the three conditions were:CO2 in the growth period > in the
freezing-thawing period > in the freezing period. The CO2 concentrations in the
growing period were much higher than in the freezing-thawing period and freezing
period. The CO2 concentration was the highest in the UG79, and the lowest was in
the CG. The concentration of CO2 in different soil layers was ordered as 20 cm >=
50 cm >= 35 cm >= 10 cm >= 5 cm at the UG79 and UG99 sites, and 50 cm >= 35 cm >=
20 cm >= 10 cm >= 5 cm at the CG site. 2 The spatial and temporal variation of
N2O concentration in the soil profile was different from that of CO2. While the
UG79 and UG99 sites showed a "single peak type" change, the CG site had a
"bimodal" pattern. The N2O concentration of the three conditions increased
sharply during the soil freezing-thawing period, and the N2O was also released
weakly during the growing season at the CG site (P<0.05). The average N2O
concentration of the CG was significantly higher than that of UG79 and UG99
(P<0.05). The results show that the concentration of N2O in different soil layers
was ordered as follows:UG79:20 cm >= 50 cm >= 35 cm >= 10 cm >= 5 cm; CG:50 cm >=
35 cm >= 20 cm >= 10 cm >= 5 cm, and UG99:35 cm >= 50 cm >= 20 cm >= 10 cm >= 5
cm. The results concluded that grazing decreased the profiled soil CO2
concentration and increased N2O concentration, which provides a basis for the
accurate estimation of greenhouse gas emissions in the seasonal frozen soil in
grasslands.
PMID- 29965535
TI - [Characteristics of CO2 Flux in a Mature Apple (Malus demestica) Orchard
Ecosystem on the Loess Plateau].
AB - Apples (Malus demestica) in the Loess Plateau region are grown in the largest
apple orchards in the world and China, playing an important role in the
improvement of the ecological environment. However, there is little research on
the scale of the ecological system of the apple orchard in the Loess Plateau
region. In this study, the CO2 flux of a mature apple orchard in the Loess
Plateau region was observed using an eddy covariance technique in the Shannxi
Province. Based on the observation data sets observed from January 2016 to
December 2016, a quantitative analysis of the apple orchard net ecosystem
exchange (NEE), ecosystem respiration (Reco), total ecosystem primary
productivity (GPP) changes at different time scales, changes in main
meteorological factors, the effects of soil temperature (Ts) and air temperature
(Ta) at different levels, and PAR on NEE were discussed. The results showed that
during the study period, the apple orchard ecosystem NEE monthly totals were
positive (as a carbon source) in the non-growing season in December, January,
February and March, were negative (a carbon sink) in the growing season from
April to November, and functioned as a strong carbon sink year round. The maximum
peak NEE (absolute value) monthly average daily change appeared in August[-17.08
MUmol .(m2 .s)-1], and the smallest peak appeared in November[-4.47 MUmol .(m2
.s)-1] during the growing season. The NEE monthly average daily change value
during the non-growing season is very weak, though the change is not obvious.
GPP, Reco, and NEE maximum daily total values were 11.12, 5.04, and -7.34 g .(m2
.d)-1, respectively. GPP, Reco, and NEE maximum monthly total values were 238.97,
105.38, and -144.44 g .(m2 .month)-1, respectively, as GPP and NEE maintained
high cumulative values that were relatively stable from May through August. The
annual GPP, Reco, and NEE were 1223.2, 525.2, and -698.0 g .(m2 .a)-1. The
observations show that the mature apple orchard ecosystem in the Chinese Loess
Plateau has a relatively high carbon sequestration capacity. Nighttime ecosystem
respiration Reco.n was positively correlated with the soil temperature and air
temperature at different levels, and the correlation coefficients were Ts-5 cm >
Ts-10 cm > Ta-4 m > Ta-8 m, The photosynthetic active radiation (PAR) can explain
more than 80% of the daytime NEE changes.
PMID- 29965536
TI - [Effects of Biochar Application Rates on Greenhouse Gas Emissions in the Purple
Paddy Soil].
AB - In order to explore the effects of different amounts of biochar applied in purple
paddy soil on greenhouse gas (GHG) emissions, potted experiments using a static
opaque chamber and gas chromatography method were used to study the regulations
and influences of biochar on soil greenhouse gas emission using five
treatments:no fertilizer (CK), conventional fertilization (NPK), 10 t .hm-2
biochar+NPK (LBC), 20 t .hm-2 biochar+NPK (MBC), and 40 t .hm-2 biochar+NPK
(HBC). 1 Soil CH4 emission flux reduced significantly with all biochar
application treatments; the emission flux followed the order, from large to
small, of NPK > CK > LBC > MBC > HBC. The CH4 emission flux of each treatment
showed a single peak curve, and the peak value was mainly concentrated in the
late growth stage of the paddy cropland. During the entire observation period,
the emission flux of CH4 was between -0.05 mg .(m2 .h)-1 and 47.34 mg .(m2 .h)-1.
The CO2 emission flux of each treatment was complicated and ranged from 32.95 mg
.(m2 .h)-1 to 1350.88 mg .(m2 .h)-1. The CO2 emission flux of the LBC and MBC
treatments showed bimodal curves, and the CO2 emission flux of other treatments
showed single peak curves. In addition, all biochar treatments delayed the peak
time of the CO2 emission flux. The N2O emission flux of each treatment ranged
from -309.39 to 895.48 MUg .(m2 .h)-1, and the N2O emission flux of the LBC
treatment showed a bimodal curve, while other treatments showed single peak
curves. 2 Compared with the CK treatment, biochar treatment can significantly
reduce the cumulative emissions of CH4 and promote the cumulative emissions of
CO2 and N2O. The average amount of CH4 cumulative emissions followed the order CK
> LBC > MBC > HBC, while the average amount of CO2 cumulative emissions followed
LBC > MBC > HBC > CK, and the average amount of N2O cumulative emissions followed
HBC > MBC~LBC > CK. Compared with conventional fertilization treatment, different
application rates of biochar addition significantly reduced CH4 and CO2
emissions. As more biochar was added, CH4 and CO2 cumulative emissions were
lower. Although the regulation of N2O cumulative emissions on biochar addition
was not obvious, the application of nitrogen fertilizer could promote the
emission flux of N2O to some extent. 3 Over the time scale of 100 years, the
integrated global warming potentials (GWP) of CH4 and N2O emission under
different biochar treatment were decreased significantly, indicating that biochar
combined with chemical fertilizer is an effective GHG emission reduction measure.
PMID- 29965537
TI - [Short-Term Effects of Different Fertilization Treatments on Greenhouse Gas
Emissions from Northeast Black Soil].
AB - A 7-day incubation experiment was conducted at 25C with 60% water holding
capacity (WHC) to study the short-term effects of different fertilization
treatments on the regularity of greenhouse gas emissions from northeast black
soil. The results showed that application of chemical N fertilizer had no effect
on CO2 emission, as compared with the non-fertilizer control treatment; however,
a combined application of N fertilizer with pig manure or straw increased CO2
emissions by one magnitude compared to that of the chemical N fertilizer
treatment, with the effect of chemical N fertilizer and straw being more
prominent. Nitrification was the main process resulting in N2O emission for the
non-fertilizer control and chemical N fertilizer treatments, and the application
of chemical N fertilizer had no significant effect on N2O emission, as compared
with the non-fertilizer control. The combined application of N fertilizer with
pig manure or straw promoted the occurrence of denitrification and increased N2O
emissions by two magnitudes compared to that of the chemical N fertilizer
treatment, with the effect of chemical N fertilizer with straw being more
remarkable. Compared with the non-fertilizer control, the application of chemical
N fertilizer inhibited CH4 emissions and promoted the slightly absorption of CH4,
while the combined application of chemical N fertilizer with pig manure or straw
increased significantly the emission of CH4.
PMID- 29965538
TI - [Eukaryotic Micro-plankton Community Diversity and Characteristics of Regional
Distribution in the Yellow Sea by ITS High-throughput Sequencing].
AB - Eukaryotic micro-plankton plays a key role in the marine biotic community and in
maintaining the stability of the marine ecosystem. In order to determine the
diversity and characteristics of eukaryotic micro-plankton in the Yellow Sea,
Illumina high-throughput sequencing, based on gene markers of ITS, was conducted.
An analysis of the relationship between community structure and environmental
factors was conducted as well. The results are summarized in the following. 1
Various of species of fungi, phytoplankton, and zooplankton were obtained by high
throughput sequencing technology; for OTUs, the order is fungi > phytoplankton >
zooplankton, and for reads, the order is fungi > zooplankton > phytoplankton. 2
In different waters, species abundance and diversity differed from each other.
The Ace index and Chao1 index demonstrated an ordering of southern Yellow Sea >
northern Yellow Sea > northern East Sea > Cold Water Mass; however, for the
Simpson index and Shannon-Wiener index, the tendency followed the order of
northern East Sea > northern Yellow Sea > southern Yellow Sea > Cold Water Mass.
Species abundance and diversity in the Cold Water Mass were lowest. 3 The reads
and OTUs of fungi, phytoplankton, and zooplankton increased as temperature rose.
The reads and OTUs of fungi increased as salinity increased, while there was an
opposite trend for phytoplankton and zooplankton. Latitude was another
significant factor. In the range of 30 degrees to 40 degrees north latitude,
the Shannon-Wiener index for fungi and zooplankton indicated an increasing
tendency with an increase in latitude, while the Shannon-Wiener index for
phytoplankton showed an opposite trend. With a greater distance from the coast,
the Shannon-Wiener index of fungi, phytoplankton and zooplankton was lower. This
is the first study that amplifies the use ITS in the research of marine
eukaryotic micro-plankton, giving an enriched understanding of eukaryotic micro
plankton. The feasibility of applying high-throughput sequencing technology in
the sea is proven, and this will provide a reference for other researchers.
PMID- 29965539
TI - [Influence of Different Patterns of Discharge on Microbial Diffusion in Municipal
Treated Wastewater].
AB - Numerous pathogens exist in treated wastewater, leading to possible population
health and ecological security risks when treated waste water is reused or
discharged. To investigate the influence of different patterns of discharge on
microbial diffusion in the municipal treated waste water, high-throughput
sequencing technology was used to analyze the bacterial community structure,
dominant flora, and typical pathogens. It was found that those bacteria were
distributed in 58 classes. There were 32 species with a relative abundance of
more than 1%. While there were only 41 classes in the water sample taken as a
direct discharge to the sea, and there were 28 species with relative abundances
of more than 1%. The water sample collected as a discharge to the sea through a
river displayed higher bacterial diversity than the sample collected as a direct
discharge to the sea, indicating that the microorganisms in the treated waste
water was more likely to diffuse in when directly discharged to the sea. The
relative abundance of dominant bacteria decreased with an increase in the
diffusion distance, while the relative abundance of Cyanobacteria increased as
the diffusion distance increased. The relative abundance in the water sample
collected as a discharge to the sea through a river was higher. The dominant
bacteria in the two systems are to Proteobacteria, Bacteroidetes, and Firmicutes.
However, the dominant bacteria at the class and species levels quite dissimilar
in the two systems. The bacterial diversities near the outfall were much higher
than that in the seawater (blank sample), and the abundance was higher, which
related to sewage treatment. In addition, there was a certain amount of pathogens
and potential pathogens, including Pseudoalteromonas haloplanktis and Pseudomonas
anguilliseptica, which were highly pathogenic. Their relative abundances were
still higher after dilution. Arcobacter spp. was related to human and animal
diarrhea and bacterial and other diseases. Therefore, the detection of these
types of bacteria when the treated waste water is discharged is very important.
PMID- 29965540
TI - [Impact of Tourism on Bacterial Communities of Karst Underground River: A Case
Study from Two Caves in Fengdu, Chongqing].
AB - In this research, the bacterial community compositions of underground water in a
tourist and pristine cave were studied. Xueyu Cave and Shuiming Cave are tourist
and pristine caves, respectively, in the same karst cave system located in
Chongqing, southwest China. To understand the impact of tourism on bacterial
community compositions in underground water that flows through the caves,
filtered materials from water were collected, and 16S rDNA gene sequences were
obtained by high-throughput sequencing. The Shuiming Cave (the pristine cave) had
less diversity than Xueyu Cave (the tourist cave) based on the Shannon's
diversity index according to Illumina operational taxonomic units (OTUs).
Proteobacteria, represented mostly by gamma-Proteobacterium and Bacteroidetes,
dominated both systems. OTUs from Shuiming Cave were dominated by 38%
Proteobacteria, 24% Chlorobi, and 19% Bacteroidetes. In the Xueyu Cave, OTUs from
upstream samples were comprised of 62% Proteobacteria but comprised 64% in the
downstream samples. In the Xueyu Cave, Bacteroidetes accounted for 11% of the
total OTUs in the upstream sample and 16% in the downstream. Among the gamma
Proteobacterium and Bacteroidetes, Acinetobacter, Pseudomonas spp., and
Flavobacteriaceae, which are related to potentially pathogenic species, were
prevalent in the Xueyu Cave, while Methylococcaceae-uncultured, Methylomonas
spp., and Methylobacter, all methane-oxidizing bacteria, had high relative
abundances in the Shuiming Cave. These results revealed that potentially more
pathogenic bacteria are present in the stream waters from the tourist cave, which
has important implications for the protection of tourist caves. The RDA analysis
of the environmental factor and bacteria community in groundwater showed that the
distribution of pathogenic bacteria was positively correlated with the cave air
CO2, and the Spearman correlation analysis of the two environmental factors
indicated that the influence of the number of tourists on the structure of the
bacterial community in the groundwater was more obvious and led to the
disappearance of a large number of native bacteria. We proposed that tourist
caves control the number of daily tourists and that they enter in batches and
increase the import and export of closed devices to avoid the cave air exchange
inside and outside. In addition, it was recommended that they increase the import
and export of sterilization devices to reduce tourists with bacteria and organic
matter, and avoid leaving garbage in the hole to avoid cave microbial exchange
inside and outside. A reduction in the fixed lighting inside caves should be
required to reduce long exposure, since the tourists can bring individual source
lighting.
PMID- 29965541
TI - [Diversity of the Microbial Community in Rice Paddy Soil with Biogas Slurry
Irrigation Analyzed by Illumina Sequencing Technology].
AB - In order to explore the variation in soil microbial community diversity in paddy
fields with different irrigation periods, we collected in situ rice field soils
during different biogas irrigation periods and analyzed the microbial community
structures of these soils by high-throughput sequencing. The results showed that
as the biogas irrigation period increased, the soil pH decreased gradually, while
organic matter, nitrate nitrogen, phosphate, and other nutrients were
accumulated. Years of continued biogas irrigation was not conducive to improving
rice yields. The results showed that as the biogas irrigation period increased,
the richness in microbial species in paddy soils decreased gradually, and the
diversity in the microbial communities was also reduced. Proteobacteria accounts
for the largest proportion in rice paddy soil with biogas slurry irrigation. With
the increase of biogas irrigation years, the proportion of beta-Proteobacteria,
Bacteroidia, Bacteroidales, Burkholderiales, Bacteroides, and Thiobacillus
increased, while the proportion of Gemmatimonadetes and alpha-Proteobacteria
decreased gradually. Dissolved organic carbon (F=2.67, P=0.09) had the greatest
effect on microbial community structures in the studied paddy soils.
PMID- 29965542
TI - [Effect of Biochar Amendment on Physicochemical Properties and Fungal Community
Structures of Cinnamon Soil].
AB - To identify the effect of biochar addition on soil abiotic and biotic properties
and provide evidence for the soil improvement with biochar input, the soil
physiochemical properties and fungal community were investigated in a cinnamon
soil after 3-year biochar additions of 10, 20, and 40 t .hm-2. The relationship
between the fungal community and edaphic physicochemical characteristics was also
analyzed. The results showed that soil pH, moisture, total nitrogen (TN), and
total organic carbon (TOC) significantly increased but dissolved organic carbon
(DOC) content and soil bulk density decreased with biochar addition. High
throughput sequencing results indicated that biochar amendment had little
influence on fungal alpha diversity but significantly changed the fungal
community structure. The taxonomic classification showed that the dominant fungal
phyla were Ascomycota, Zygomycota, and Basidiomycota, and these phyla accounted
for more than 90% of the total sequences. The relative abundance of Ascomycota
and Basidiomycota increased, while the abundance of Zygomycota decreased with
biochar addition. At the genus level, biochar addition increased the relative
abundances of Alternaria, Conocybe, and Aspergillus but decreased the relative
abundances of Actinomucor and Gibberella. Redundancy analysis (RDA) showed that
soil DOC, pH, and moisture were key environmental factors leading to the shift in
the soil fungal community composition. In summary, the application of biochar
changed the soil physicochemical properties, which drove the ecological
succession of soil fungal communities.
PMID- 29965543
TI - [Carbon Metabolism Characteristics of the Karst Soil Microbial Community for Pb
Zn Mine Tailings].
AB - BIOLOG and 18S rRNA PCR-DGGE methods were used to estimate the characteristics of
carbon source metabolism of the soil microbial community as well as the
relationship between soil fungi and soil organic carbon in different karst land
use types (corn field, citrus field, and paddy field) contaminated by Pb-Zn
tailings at Sidi Village, Yangshuo, Guangxi Zhuang Autonomous Region, SW China.
It was found that the concentrations of Pb, Zn, Cu, and Cd were highest in the
paddy field, followed by the corn field, citrus field, and control group (dry
field). In addition, the geo-accumulation index indicated that the heavy metal
pollution at this area was caused by Pb and Cd and that Cd was the key
environmental risk factor. With the Pb-Zn tailings, there was low microbial
biomass carbon, biological entropy, and microbial carbon source metabolism in the
soil samples. The highest soil organic carbon and heavy metal concentrations were
found in the paddy field, followed by the corn field and citrus field. According
to the DDGE results, it was found that Pycnoporus sp. ZW02.30 was found in
control group soils, Fusarium solani and Fusarium oxysporum were found in the
corn field and citrus field, and Penicillium decumbens was found in citrus field.
These were involved in the degradation of sugars, such as starch, cellulose,
hemicellulose, and lignin. However, the fungi were not found in the paddy field.
Based on the low functional diversity of the soil microbial community and
biological entropy as well as the high soil organic carbon concentration in the
paddy field, it was concluded that soil microbial carbohydrate metabolism and the
mineralization rate of the soil organic carbon was controlled by soil
microorganisms, especially fungi, in different land use soils in the karst area
contaminated by Pb-Zn tailings.
PMID- 29965544
TI - [Denitrification Characteristics and Community Structure of Aerobic Denitrifiers
from Lake and Reservoir Sediments].
AB - The effect of aerobic denitrifying bacteria is a hot topic in the field of water
environment bioremediation. Aerobic denitrifier communities, H-30, X-10, and C
30, enriched by intermittent aeration, screened with screening culture media, and
treated by ultrasonic waves, could perform high denitrification performance at
the higher dissolved oxygen concentration of (7.2+/-0.6) mg .L-1. The total
nitrogen (TN) removal rate of aerobic denitrifier communities, H-30, X-10, and C
30, reached 83.04%, 83.40%, and 82.68%, respectively. There is lower nitrite
accumulation during the process of denitrification. Illumina high-throughput DNA
sequencing revealed that aerobic denitrifier compositions were significantly
different among the three communities. The predominant strains of aerobic
denitrifier communities, H-30, X-10, and C-30, were Bacillus subtilis, Paracoccus
pantotrophus, and Pseudomonas stutzeri, respectively. The proportion of P.
stutzeri in aerobic denitrifier communities H-30 and X-10 was almost the same,
while Pseudomonas xiamenensis was only detected in H-30. These three efficient
aerobic denitrifier communities provide a bacterium source guarantee for polluted
water bioremediation of lakes and reservoirs in cities.
PMID- 29965545
TI - [Investigation of the Coupling Mechanism Between Naphthalene Degradation and
Denitrification of a Naphthalene Degraded Bacterial Consortium Under
Denitrification].
AB - To investigate the coupling mechanism between naphthalene degradation and
denitrification using a liquid media containing naphthalene (sole carbon source)
and nitrate, a naphthalene degradation bacterial consortium under denitrification
was enriched from a soil with potential risk of PAH (polycyclic aromatic
hydrocarbon) contamination. The bacterial community composition of the enriched
consortium was analyzed by Illumina MiSeq Sequencing. Subsquently, the enriched
consortium was cultured under anaerobic conditions for 9 days, and the
concentrations of electron acceptors (nitrate and nitrite) for denitrification,
gaseous reduction products (N2O and N2) involved in denitrification, and
abundances of denitrification concerned genes (narG:periplasmic nitrate
reeducates gene; nirS:cd1-nitrite reductase gene) were detected at days 1, 3, 7,
and 9. The result of Illumina MiSeq Sequencing showed that Pseudomonas
(Proteobacteria) was the most dominant genus in this enriched consortium. Under
anaerobic conditions, the naphthalene removal rate of this enriched consortium
was 49.11% within 9 days. Relative higher naphthalene degradation rates were
found both at the beginning (day 1-3) and the end (day 7-9) of incubation, and
these were significantly higher than at the middle (day 3-7) of the incubation
stage (P<0.05). The concentration of nitrate decreased during the whole culture
period, while the concentration of nitrite increased during the initial
incubation (day 1-3) and rapidly decreased from day 3 to 9. Furthermore, obvious
productions of N2O[3.39 MUg .(L .h)-1] and N2[8.97 MUg .(L .h)-1] were only
measured at the end of incubation (day 7-9). The abundances of both narG and nirS
increased during the incubation, indicating the continuous growth of denitrifiers
in the enriched consortium during the incubation period. In summary, this study
illustrated that both the nitrate reducing stage and gas producing steps of
denitrification could be coupled with anaerobic naphthalene degradation, which
might be helpful for a deeper investigation regarding the coupling mechanism
between denitrification and anaerobic PAH degradation.
PMID- 29965546
TI - [Spatial Distribution Study and Pollution Assessment of Pb in Soils in the
Xijiang River Drainage of Guangxi].
AB - To obtain data for the accumulation of Pb and its risk in soils in the Xijiang
River drainage of Guangxi, 2594 samples were collected from nonferrous metal
mining soils, farmland soils (paddy soils and dryland soils), and the background
soils in the drainage area. Geostatistical analysis combined with GIS was used to
study the soil spatial distribution characteristics and pollution distribution of
the soil Pb content. The results showed that the Pb background value of the soil
was 51.84 mg .kg-1 in the Xijiang River Basin, and the results of the single
sample T test showed that the soil background value was significantly higher than
that of a previous study (22.08 mg .kg-1) and the soil background value (20.50 mg
.kg-1) in Guangxi province. The geometric mean concentration of Pb in the mining
soils, dryland soils, and paddy soils were 655.9, 116.7, and 40.63mg .kg-1,
respectively, significantly higher than that in other soils. Using GB 15618-1995
and the baseline as the limiting value, the corresponding exceedance rate of the
mining soils, dryland soils, and paddy soils were 57.69%, 16.40%, and 8.92% and
54.95%, 8.09%, and 2.03%. The mining soils and farmland soils had an obvious lead
accumulation trend. There was an obvious spatial autocorrelation of Pb in the
soil, and the structural variation was dominant. The content of Pb in the upper
reaches of the Xijiang River reached the middle and lower reaches of the Xijiang
River, and the soil Pb was characterized by an obvious decrease. The accumulation
of high Pb content in the upper reaches of Diaojiang River is much larger than
that in the lower reaches of Diaojiang River. The content of Pb in soil samples
in the Xijiang River Basin was mainly rated between mild pollution and moderate
pollution, and the pollution was concentrated in the municipal administrative
area and the mining activity area. The pollution of the soil in Jinchengjiang and
Nandan counties was closely related to the frequent local mining activities.
PMID- 29965547
TI - [Effects of Agricultural Activities on Soil Mercury Changes in the Water-Level
Fluctuating Zone of the Three Gorges Reservoir].
AB - Farming in the water-level-fluctuating zone (WLFZ) of the Three Gorges reservoir,
China, may result in a wide range of environment problems when the sediment is
exposed to air. In this study, Qukou, Chongqing, was selected as the research
site due to its large WLFZ area and significant agricultural activities. Four
kinds of land use types, including rice, maize, vegetables, and grassland, were
selected to investigate the distribution of mercury (Hg) in the surface soil. The
results showed that the mean concentrations of soil total Hg (THg), bioavailable
Hg (Hg-wh), and methylmercury (MeHg) in the surface soil were 25.80-68.74 ng .g
1, 0.44-0.88 ng .g-1, and 0.08-0.85 ng .g-1, respectively. The concentrations of
THg, Hg-wh, and MeHg in non-cultivated soil were higher than those in cultivated
soil, indicating that farming disturbances could accelerate soil Hg loss. The
MeHg concentrations in both non-cultivated and cultivated soil increased up to
the maximum value 1-2 months after drying, and then gradually decreased to a
relatively stable level. The peak value was approximately four times higher than
that at the end of flooding. The percentage of MeHg to THg (% MeHg) was similar
to the distribution of soil MeHg, and the peak value occurred at 1 month after
drying. However, when% MeHg decreased to the stable level, no significant
difference was found compared to the value at the end of flooding (P>0.05).
Furthermore, the soil% MeHg had a significantly positive correlation with Hg-wh
(r=0.642, P<0.01), while there was no significant correlation with THg (P>0.05),
suggesting that Hg methylation was mainly affected by the bioavailability of Hg
in the seasonally inundated soil of the WLFZ.
PMID- 29965548
TI - [Screening and Identification of Arsenic-resistant Endophytic Bacteria from
Different Rice Tissues (Oryza sativa L.) in Different Growth Stages].
AB - Soil microorganisms are critical for arsenic transport and transformation in the
soil-plant system. Endophytes are a very rich microbial resource, but to date no
study has reported the responses of endophytes to arsenic pollution. In this
study, the cultivable endophytic bacteria were isolated from the root, stem,
leaf, and panicle of rice (Oryza sativa L. cv. Yongyou-538) at the seedling
stage, tillering stage, flowering stage, and productive stage. All isolates were
first screened by 1 mmol .L-1 arsenite[As (III)] and 10 mmol .L-1 arsenate[As
(V)], and further screened by 2 mmol .L-1 As (III) and 20 mmol .L-1 As (V). From
this study, a total of 126 strains of rice endophytes were obtained, belonging to
13 genera. Among them, 37 strains (8 genus) were isolated from the rice seedling
stage, 25 strains (5 genus) were isolated from the rice tillering stage, 24
strains (8 genus) from the rice flowering stage, and 30 strains (8 genus) from
the rice productive stage. The dominant genera were Bacillus sp., Psoudomonas
sp., and Acinetobacter sp. After twice screening, 20 strains were found to be
resistant to 1 mmol .L-1 As (III) and 10 mmol .L-1 As (V), including 16 strains
that were resistant to 2 mmol .L-1 As (III) and 13 strains were resistant to 20
mmol .L-1 As (V). Importantly, the strain CS1 was found to be the most resistant
bacteria to both As (III) and As (V) among all the isolated strains.
PMID- 29965549
TI - [Characteristics of Mercury Transformation in Soil and Accumulation in Rice
Plants in an Acidic Purple Paddy Soil Area].
AB - A pot experiment was conducted to analyze the characteristics of mercury (Hg)
accumulation during the rice growth period in acidic purple paddy soil. Results
showed that the soil total Hg concentration was stable with time during the rice
growth period, while methylmercury (MeHg) increased greatly. Therefore, the ratio
of MeHg/THg was mainly affected by MeHg concentration. THg concentration in rice
plant parts followed the trend:root > grain > stalk > leaf > husk at the mature
grain stage, while MeHg concentration followed grain > root > stalk > leaf >
husk. The average of MeHg/THg in rice (24.03%) far exceeded that in soil (3.05%),
suggesting that rice plants have a strong affinity for MeHg accumulation. This
conclusion was supported also by the great difference in average of bio
concentration factors between MeHg (8.16) and THg (2.31) or the transfer factor
in the grain, which was more than 1. Moreover, the bio-concentration factor for
grain was higher than that for roots, stalks, and leaves, suggesting MeHg was
prone to accumulation in grain compared with other part of rice plants.
PMID- 29965550
TI - [Life Cycle Environmental Impact Assessment on Different Modes of Greenhouse
Vegetable Production in the North China Plain].
AB - Organic agriculture has a higher potential than traditional agriculture to reduce
environmental emissions. However, heavy metals in organic manure inevitably
exacerbate eco-toxicity. At present, there are few studies on systematically and
comprehensively evaluating the effects of different production modes on the
environmental impact of vegetable production in the North China Plain (NCP). The
objective of this study is to provide a theoretical direction for reducing the
negative impact of greenhouse vegetable production. In this study, we used a
greenhouse eggplant production (2013-2016) as case study and conducted a field
experiment in Quzhou County, Hebei Province, China. The life cycle assessment
(LCA) approach was used to analyze and compare the production and environmental
impacts of eggplant production under three modes:conventional, integrated, and
organic. The results showed that the potential for water contamination,
eutrophication, and soil contamination was high among the three modes, ranging
from 82.05% to 84.02%, 10.29% to 12.32%, and 2.62% to 3.48%, respectively. This
is occurred mainly in the arable farming subsystem and is attributed to the loss
of nitrogen (N) and phosphorus (P), pesticide residues, and heavy metals in
organic manure. The environmental impact index of the integrated mode is the
lowest, with a value of 0.596, which is 30.3% and 6.7% lower than those of the
conventional and organic modes. The integrated mode significantly reduces the
emission of pollutants from the greenhouse vegetable production in the arable
farming subsystem; therefore, it is the best management practice. In the
integrated mode, the environmental costs of producing one ton of eggplant are
46.6 J for energy depletion, 81.9 m2 for land occupation, 0.0046 m3 for water
depletion, 0.0054 kg (CO2-eq) for global warming, 0.0060 kg (SO2-eq) for
acidification, 0.0735 kg (PO4-eq) for aquatic eutrophication, 2.84E-05 kg (1,4
DCB-eq) for human toxicity, 0.4892 kg (1,4-DCB-eq) for aquatic eco-toxicity, and
0.0174 kg (1,4-DCB-eq) for soil eco-toxicity. Optimizing field management
measures such as the application of biological pesticides, using high quality
organic fertilizer, and improving the efficiency of N and P use, can better
control the negative environmental impacts in the life cycle of vegetable
production and improve environmental sustainability in the NCP.
PMID- 29965551
TI - [Health Effects of PM2.5 Based on Bacterial Toxicity Test and Transcriptional
Analysis in Lungs of Mice].
AB - Although epidemiology and toxicology studies have demonstrated that exposure to
ambient air particles could result in a variety of lung diseases, but the
pulmonary toxicological mechanism remains obscure. In this study, the toxicity of
PM2.5 particles in different concentrations was investigated by toxicological
methods, including the luminescent bacteria acute toxicity test and genotoxicity
performed by SOS chromogenic reaction. The results indicated that, the acute
toxicity and genotoxicity were low and negative, respectively. In addition, rats
were treated with PM2.5 suspension through intratracheal instillation, and the
pathologic changes and expression of different genes in their lungs were carried
out. We found that PM2.5 exposure resulted in fibrotic changes and inflammation
in the lung with the increase in PM2.5 concentration. Pathway analysis indicated
that PM2.5 can induce pulmonary toxicity through disturbing the function of
ribosomal protein, fatty acids, and cholesterol metabolism, suggesting an
inflammatory reaction in the lung is caused by genetic damage and is
irreversible. A gene ontology analysis revealed that abnormal expression of
related genes in the immune response could be the specific pathway of lung
inflammation. These findings improve our understanding of the toxicological
pathway and mechanism of PM2.5 exposure.
PMID- 29965552
TI - [Socio-economic Factors Influencing the Spatial Distribution of PM2.5
Concentrations in China: An Exploratory Analysis].
AB - In recent years, the PM2.5 pollution in China has become a top environmental and
health concern, involving the characterization of healthy effects over a broad
spatial area with uneven geographical distribution. This research aims to explore
the influential factors for the PM2.5 distribution from a socio-economic
perspective, based on the observations from China's 1497 monitoring sites in
2015. First, the Moran's I index and the local indicators of spatial association
(LISA) were computed to outline the distribution of PM2.5 on a national scale
using provincial-level divisions. Second, the correlation between the spatial
distribution of PM2.5 and socio-economic factors were analyzed by ordinary least
squares (OLS) and geo-weighted regression (GWR) models. The results indicated
that the GWR model explained the causal relationships better. Generally, Beijing,
Tianjin, and Hebei had peak levels of PM2.5, while Guangxi, Sichuan, and several
other southern provinces had the lowest levels. Particularly, forest coverage
rate and electricity consumption per capita were negatively correlated with the
concentration of PM2.5. In this study, the vehicle ownership per capita proved to
be the most significant factor that positively contributed to the concentration.
PMID- 29965553
TI - [Reactivity-based Anthropogenic VOCs Emission Inventory in China].
AB - A reactivity-based anthropogenic volatile organic compounds (VOCs) emission
inventory in China in 2010 was developed on the basis of ozone formation
potential (OFP), using the latest VOCs emission inventory, source profiles and
maximum incremental reactivity (MIR) values. The results showed that the total
anthropogenic OFP was 84187.61 kt in China in 2010, of which 6882.53 kt was from
alkanes, 41496.92 kt from alkenes/alkynes, 32945.32 kt from aromatic
hydrocarbons, 161.45 kt from halocarbons, and 2701.40 kt from oxygenated
organics. The top 10 species in terms of OFP consisted of propene, ethene, m/p
xylene, toluene, 1-butene, o-xylene, 1,2,4-trimethyl benzene, 1,3-butadiene, m
ethyl toluene and ethyl benzene, contributing 63.95% to the total OFP but only
31.84% to the mass-based emission. Industrial sources accounted for the largest
(49.29%) of the total OFP, followed by transportation sources (28.31%) and
agricultural sources (22.40%). The key industrial sources with high reactivity
were architectural decoration industry, oil refinery industry, storage and
transport, machinery equipment industry, transport equipment industry and
printing. Passenger cars, motorcycles and heavy duty vehicles were the major OFP
sources of transportation. The two biomass burning sources were both the key OFP
sources of agriculture. Shandong, Jiangsu, Guangdong, Zhejiang and Henan were the
top five provinces with contributions of 39.65% of the total OFP in China. The
reactivity-based emission inventory in this study would be of great significance
for the formulation of reactivity-based ozone (O3) control strategies in China.
PMID- 29965554
TI - [Characteristics of Reactive VOCs Species During High Haze-Pollution Events in
Suburban Area of Shanghai in Winter].
AB - Based on the online measurements of VOCs of high pollution process at the
university site in winter, VOCs' characteristics and species at different levels
of haze pollution were analyzed. Fifty-five VOCs were detected during sampling.
?55VOCs concentrations ranged between 25.5*10-9-1320.3*10-9(avg+/-SD,240*10-9+/
181*10-9). Toluene and xylene were the major pollutants during high pollution
process, the concentrations of which were higher than those of industrial area.
The university site shared a similar VOC composition with that of industrial
area, which suggested that it might be influenced by the surrounding industries.
VOCs species exhibited high concentrations in nighttime while low concentrations
in daytime. The ozone concentrations were on the contrary. Aromatic hydrocarbons
were predominant with a high percentage of contribution (70.0%) to OFP (ozone
formation potential). Alkenes and alkynes were the second highest group (16.7%).
The OFP of VOCs was 2078.2*10-9 under the west-south wind direction, about 4
times higher than the value under other wind directions (505.8*10-9). Aromatic
hydrocarbons exhibited a predominant contribution to OFP at different levels of
haze pollution in this area, among which, Toluene and xylene contributed more
than 50% to OFP. The newest version of EPA PMF model was used to identify the
major source of VOCs and evaluate their contributions. Gasoline sources and
vehicle exhaust, refinery and petroleum products, solvent use and organic
synthetic materials were the identified VOC sources in the study area,
contributing 33.1%, 31.5%, 30.5%, and 4.9%, respectively to the ?55VOCs
concentrations.
PMID- 29965555
TI - [Assessment of PM2.5 Pollution Mitigation due to Emission Reduction from Main
Emission Sources in the Bejing-Tianjin-Hebei Region].
AB - This study chose two months (January and July) in 2012 which represent winter and
summer respectively, to assess the effects of fine particle(PM2.5) pollution
elimination due to emission control from different sectors in the Bejing-Tianjin
Hebei region by using CMAQ/2D-VBS modeling system. The results showed that,
industrial emissions contributed most to PM2.5 pollution in the Beijing-Tianjin
Hebei region, followed by domestic emissions, while the contribution of per ton
emission reduced for industrial sectors subject to domestic sectors. The total
contribution and contribution of per ton emission reduced for transportation and
power plant were both at low level. Among industrial sectors, the iron, steel and
metallurgical industry was the greatest contributor, followed by cement industry,
industrial boiler, coking industry, lime and bricks industry and chemical
industry. It was found that the contribution of each emission source had
significant association with its primary PM2.5 emission level. The control of NOx
emissions would promote the formation of PM2.5, and atmospheric vertical
diffusion effect was weak during wintertime in the Beijing-Tianjin-Hebei region.
As a result, emission control of various sectors was universally more effective
for PM2.5 pollution mitigation in summer than in winter. Emission control in
summer was significantly more effective for transportation, powerplant, cement
industry, industrial boiler and lime and bricks industry. Due to considerable
emissions in heating season, domestic emissions showed more contribution in
winter. Agricultural sources showed greater contribution per emission reduction
in winter by the reason of substantial emissions from straw open burning during
this time. With respect to a certain reduction ratio of emission, future control
strategies should pay more attention to industrial emissions, especially to the
primary PM2.5 emissions. In details, priorities should be given to NOx and SO2
emission control for iron, steel and metallurgical industry, NOx emission control
for cement industry and SO2 and NMVOC emission control for coking industry.
Besides, domestic emission control should also be taken into consideration, and
it will be more effective in winter.
PMID- 29965556
TI - [Concentration Characteristics and Sources of Trace Metals in PM2.5 During
Wintertime in Beijing].
AB - To study the characteristics and sources of trace metals in PM2.5 during
wintertime in Beijing, PM2.5 samples were collected from December 2014 to January
2015 by a middle volume sampler in the urban area of Beijing for 30 consecutive
days. The mass concentration of PM2.5 was measured by filter membrane weighting
method, and 16 kinds of trace metals were determined by inductively couple plasma
mass spectrometry (ICP-MS). In addition, the pollution characteristics and
sources of trace metals were analyzed by enrichment factor (EF) method and factor
analysis, respectively. The results showed that the concentrations of five
elements (i. e. K, Ca, Fe, Al and Mg) accounted for 90.7% of the total metal
elements. The concentrations of the metal elements changed obviously between day
and night. Compared with daytime, crustal elements like Mg and Al decreased by
more than 30% while anthropogenic elements like Cu and Pb increased by more than
40% in nighttime. Although the concentrations of metal elements increased by
nearly one time in heavy pollution days compared with clean days, the mass
percent of which in PM2.5 decreased from 10.9% in clean days to 4.6% in heavy
pollution days. This result suggested the accumulation of metal elements in heavy
pollution days had a minor contribution to the increased mass concentration of
PM2.5. As the pollution episode progressed, anthropogenic elements
(Cu,Zn,As,Se,Ag and Cd) increased faster than crustal elements (Al,Mg,Ca,Mn and
Fe), which showed ratios ranging from 2.9 to 5.3 for anthropogenic elements and
ratios ranging from 1.2 to 1.8 for crustal elements, when compared between heavy
pollution days and clean days. In addition, the EF value of anthropogenic
elements was also increased in the pollution days, indicating the concentrations
of these elements was further influenced by the anthropogenic sources. Factor
analysis showed that metal elements of PM2.5 during wintertime of Beijing were
mainly from coal combustion and biomass burning, motor vehicle and industry
emissions, and re-suspension of road dust, with the contributions of 34.2%,25.5%
and 17.1%, respectively.
PMID- 29965557
TI - [Online Source Analysis of Particulate Matter (PM2.5) in a Heavy Pollution
Process of Shijiazhuang City During Heating Period in 2015].
AB - In recent years, more and more public attention has been paid to the problem of
air pollution during the heating period in North China. This article took a heavy
pollution process of Shijiazhuang district from Nov.24th to Dec.4th in 2015 as an
example, and analyzed comprehensively the source apportionment in different
periods, size distribution of the PM2.5 from each source in different periods,
the characteristics of mass spectra of the main emission sources and the
meteorological conditions with the method of real-time online source analysis. It
turned out:the main sources of pollutants were coal combustions, industrial
discharges, vehicle exhausts and secondary inorganic reactions. With the help of
meteorological condition of low pressure and low wind speed, the PM2.5 mainly
produced by coal combustions and industrial discharges accumulated heavily and
went through the second stage conversion, leading to this heavy air pollution.
The main particulate matters from coal combustions were the mixed carbons; the
main particulate matters from industrial discharges were metals; the main
particulate matters from vehicle exhausts were elemental carbon and manganese
metal; the main particulate matters from pure secondary inorganic sources were
secondary inorganic ions; the main particulate matters from dust pollution were
aluminum, calcium, iron and silicate minerals; the main particulate matters from
biomass fuel combustions were levoglucosan; the feature signal from restaurant
discharges was organic acid. Different from the distribution before and after the
heavy pollution period, the particulate matters from the 8 pollution sources
presented even distribution during the heavy pollution period.
PMID- 29965558
TI - [Analysis of Chemical Composition and Pollution Source of the Fine Particulate
Matter by the SPAMS in the Four Seasons in Nanning].
AB - To study the chemical composition and pollution sources of the fine particulate
matter during the four seasons in Nanning, single particle aerosol mass
spectrometry was performed to characterize the fine particulate matter in Nanning
during the four seasons. The correlation (R2) between the fine particulate matter
number concentration and the mass concentration of the fine particulate matter
obtained using SPAMS was all above 0.75 in the observation period. The particle
number concentration could reflect the atmospheric pollution situation to some
degree. The average mass spectrogram of the fine particulate matter reflected
that secondary pollutants were more in winter and spring in Nanning. The Art-2a
classification method was used to classify the chemical composition of the fine
particulate matter. The results showed that the number concentration of the
chemical composition and sources of pollution had differences in the four
seasons. Chemical composition could reflect pollution sources. The elevated
elemental carbon was positively with increasing coal combustion in winter. The
elevated organic carbon was positively correlated with motor vehicle source in
autumn. Rich potassium particles, levoglucosan and substance were positively
correlated with biomass burning source and dust in summer. The rich sodium
particles and heavy metals were higher in spring. During the process of
increasing pollution, the contributions of biomass and coal combustion sources
were large.
PMID- 29965559
TI - [Physico-chemical Characteristics of Individual Aerosol Particles in Marine
Atmosphere on South Hemisphere].
AB - During the 29th Chinese National Antarctic Research Expedition (CHIANRE),
individual particle samples were collected from South China to Antarctic during
November 2012 to April 2013. A transmission electron microscopy with energy
dispersive X-ray spectrometry (TEM-EDS) was employed to analyze the morphology,
mixing state, composition, and relative abundances of individual aerosol
particles. Atmospheric particles were classified into four types:sea salt,
mineral, S-rich and C-rich. Sea salt aerosols (SSA) were dominant in the marine
particles from South China to Antarctic, and they were further divided into three
sub-types:fresh SSA, partially aged SSA, and fully aged SSA. Partially and fully
aged SSA accounted for 86% of total SSA number. Interestingly, surface of
partially aged SSA and fully aged SSA contained abundant rod-like Na2SO4. Mineral
dust particles increased in the coastal areas which were influenced by
continental air. In addition, we found that S-rich particles were abundant at two
sampling sites (the middle eastern of Indian Ocean and Antarctic inland). The
back trajectories of air masses indicated that these S-rich particles were mainly
formed via the oxidation of dimethyl sulfide (DMS) emitted from the marine
phytoplanktons. Our study suggests that the SSA aging process in the South
Hemisphere atmosphere was controlled by the DMS which is different from the SSA
aging under the influence of anthropogenic pollutants in the North Hemisphere.
PMID- 29965560
TI - [Characteristics of Spatial Distribution of Bacterial Aerosols Produced by
Fountain].
AB - To illuminate the spatial distribution of bacterial aerosols produced by
fountain, sprinkler test was conducted in this study. Escherichia coli NK5449 was
used as the test strain, and bacterial aerosols were sampled by Anderson six
stage air sampler at different sites around the sprinkler. The concentration and
particle size distribution of bacterial aerosols and the correlation between
droplet diameter and bacterial aerosols concentration were analyzed. The results
showed that the concentration of bacterial aerosols ranged from (38+/-15) CFU.m-3
to (676+/-92) CFU.m-3 in the space of 0.75 m to 1.75 m from the ground and 0.5 m
to 3 m away from the sprinkler. The bacterial aerosol concentration decreased
along with the increase of the height and the distance between the sampling site
and the sprinkler,and had significant negative correlation with droplet
diameter(P<0.05). With the increase of the distance to sprinkler, the proportion
of bacterial aerosol particles with size of larger than 4.7 MUm decreased at
first and increased subsequently; while the proportion of bacterial aerosol
particles with size between 2.1 and 4.7 MUm increased firstly and then decreased.
The bacterial aerosol particles mainly existed in the part with size between 1.1
and 4.7 MUm at sampling sites more than 0.5 m away from the sprinkler. It
indicated that bacterial aerosols with small size may be inhaled by people far
away from the fountain, and the risk should not be ignored.
PMID- 29965561
TI - [Removal of Volatile Sulfur Odor by the Biotrickling Filter].
AB - The biodegradation of gas-phase mixtrue of dimethyl sulfide (DMS) and 1
propanethiol (PT) was examined in a biotrickling filter (BTF), inoculated with a
microbial consortium composed of activated sewage sludge, and pure strains of
Alcaligenes sp. SY1 and Pseudomonas putida. S-1. BTF could be successfully
started up within only 11 days when the inlet concentrations of DMS and PT were
both 50 mg.m-3 and EBRT was 30 s, with 90% removal efficiency (RE) of DMS and
100% RE of PT. In the steady state, the maximum elimination capacities of DMS and
PT were 8.7 g.(m3.h)-1 and 12.4 g.(m3.h)-1, respectively. The presence of PT with
a concentration up to 51 mg.m-3 showed an antagonistic removal pattern for DMS,
but the opposite did not occur. Meanwhile, the BTF showed high efficiency in the
biodegradation of H2S. When the concentration of H2S was as high as 230 mg.m-3,
the RE of H2S could reach 98%. However, H2S showed a declining effect on the
removal of DMS when the concentration exceeded 115 mg.m-3.
PMID- 29965562
TI - [Magnetic Characteristics and Environmental Pollution Analysis of Street Dust in
Different Functional Zones of Xi'an City].
AB - Urban environmental pollution can be revealed by the magnetic characteristics of
street dust. Environmental magnetic measurements were carried out for the 151
samples of street dust collected in different functional zones of Xi'an city.
Magnetic susceptibility varied within the range between 169.5*10-8 m3.kg-1 and
977.48*10-8 m3.kg-1, and the chilf average value was 415.66*10-8 m3.kg-1,which
was 10 times higher than that of the background value. Isothermal remanent
magnetization varied within the range between 2005.31*10-5 A.m2.kg-1 and
10897.64*10-5 A.m2.kg-1, and the SIRM average value was 5105.99*10-5 A.m2.kg-1.
The average value of frequency-dependent magnetic susceptibility was 1.30, which
was extremely low. The SIRM curve was consistent with chilf curve. The results
indicated a high concentration of magnetic minerals in street dust. The magnetic
minerals were mainly low-coercivity ferrimagnetic (magnetite and maghemite) and
anti-ferromagnetic minerals (hematite), which contributed to the magnetic
susceptibility. The main domains of magnetic minerals were composed of multiple
domain (MD) and pseudo-single domain (PSD) ferrimagnetic minerals demonstrating
the pollution of environment. According to the spatial distribution of magnetic
properties of street dust and the different functional zones of Xi'an city, seven
districts (A, B, C, D, E, F and G areas) were divided, which were summarized as
three pollution types:heavily polluted, moderately polluted and lightly polluted.
In the ecological district of Baqiao (F area) which was heavily polluted, chilf,
SIRM and soft values were all the highest in the seven areas, and the main
pollution sources were industry and vehicle emission. chilf, SIRM and soft values
were slightly higher in the high-tech industrial district (A area) and the
central business and commerce district (B area), which was moderately polluted by
industry and vehicle emission. However, the magnetic parameters were relatively
low in the functional zones of education, tourism and culture (C, D, E and G
area), demonstrating that these areas were only slightly polluted by vehicle
emission.
PMID- 29965563
TI - [Pollution Characteristics and Nitrification and Denitrification Potential of
Superficial Sediments from Streams in an Urban-Rural Fringe].
AB - From May 2015 to June 2016, seasonal sediment samples were collected from three
headwater streams in the urban-rural fringe of Hefei, Chaohu Lake basin, China.
The nitrogen pollution characteristics of sediments were preliminarily
investigated for the three streams. Three metrics, that is, potential
nitrification rate (PNR), areal nitrification rate (ANR) and rate of
denitrification were quantitatively determined, and their spatial and temporal
variations were discussed subsequently. Moreover, the relationship between PNR,
ANR or denitrification rate and a list of environmental factors was discriminated
by using partial least-squares regression analysis. Results showed that:1
Guanzhenhe Distributary was the most polluted stream with a mean content of
4516.39 mg.kg-1 for TN, which was 2.56 and 1.36 times higher than those of Modian
Stream and Taochong Stream, respectively. Similarly, the highest values for NH4+
N and NO3--N emerged in Guanzhenhe Distributary while the lowest existed in
Modian Stream. 2 There were distinct seasonal variations in PNR and ANR, namely,
the maximum values emerged in summer, minimum in winter, and almost equivalent in
spring and autumn. And the arrangement in order for PNR and ANR was Taochong
Stream > Modian Stream > Guanzhenhe Distributary. 3 The mean rate of
denitrification in Guanzhenhe Distributary was 10.59 mg.(kg.h)-1, which was 3.16
and 1.75 times higher than those in Modian Stream and Taochong Stream,
respectively. In addition, both denitrification rate and denitrification activity
in summer were higher than those in spring for the three streams. 4 According to
the variable importance plot (FVIP), ANR, PNR and rate of denitrification were
almost all significantly correlated with such physical and chemical factors as
pH, OM, NH4+-N, NO3--N, TN and TP in sediments for the three streams.
PMID- 29965564
TI - [Nitrification and Denitrification Rates in a Small Tributary, Nanhe River, of
Three Gorge Dam Reservoir During Water Collection and Release Events].
AB - Three Gorge Dam Reservoir (TGDR) is a new forming ecosystem and its sediments
dynamics remains unknown. Investigation on the nitrification and denitrification
dynamics of sediments of TGDR during water collection and release events-anti
seasonal actions-is critical for nitrogen management in TGDR. In this study, we
sampled sediments in three locations (upstream, center, and downstream along
water flow) of South River, located in a typical small tributary, Nanhe, in TGDR
during 2015 water collection and release events to characterize its
physiochemical property and determine its nitrification and denitrification rates
using acetylene inhabitation method. The results showed that the concentrations
of physiochemical parameters of sediments (total carbon, total nitrogen, nitrate,
and ammonia) were significantly higher (P<0.05) in water collection event than
those in water release event, suggesting there were external materials (e. g.,
soil) entering into TGDR. Furthermore, the nitrification rate of sediments in
water collection event[194.06 MUmol.(m2.h)-1] was significantly higher than that
in water release event[16.52 MUmol.(m2.h)-1]. Sediments nitrification rate was
positively correlated to the physiochemical parameters. In contract, the
denitrification rate of sediments was higher in water release event[647.20
MUmol.(m2.h)-1] than that in water collection event[24.04 MUmol.(m2.h)-1).
Accordingly, the denitrification rate of sediments was negatively correlated to
the physiochemical parameters.
PMID- 29965565
TI - [Tempo-spatial Variations and Influential Factors of Carbon Dioxide Emissions
from the Geheyan Reservoir over the Qingjiang River Basin, China].
AB - Greenhouse gas emission from aquatic ecosystem will affect climate change on the
regional and global scale. So large river interception project which affects the
carbon cycle model and greenhouse gas emission from aquatic ecosystem has
provoked more and more attentions in recent years. In order to understand and
evaluate the effects of typical hydropower project construction on the aquatic
ecosystem and carbon cycle, the Geheyan Reservoir, a typical river interception
project, was selected as a typical case in this paper for measuring carbon
dioxide fluxes from interface between water and atmosphere from March, 2015 to
February, 2016. The integration of the online gas analyzer and floating box was
used to obtain carbon dioxide fluxes from interface between water and atmosphere.
Data was obtained over the before dam, upstream, tributary, drawdown area and bay
area respectively for understanding the spatial Heterogeneity of carbon dioxide
fluxes. Data analysis showed that yearly mean fluxes of carbon dioxide from the
Geheyan Reservoir was (55.6918+/-66.3329) mg.(m2.h)-1 during measurement, which
indicated that the temporal distribution was higher in winter and lower in other
seasons and the spatial variation was higher in typical bay and lower before dam
as well as drawdown zone over the reservoir. Moreover, the seasonal variation of
carbon dioxide fluxes from the interface between water and atmosphere was very
stable at Yuxiakou measurement points as a typical background area of the
reservoir, which was unexpectedly higher than those before dam and drawdown zone
in the most months during measurement. The results from data analysis also
indicated that the spatial and temporal variation of carbon dioxide fluxes from
the Geheyan Reservoir was affected by water quality parameters such as dissolved
oxygen, chlorophyll, pH, water temperature and conductivity and carbon in water,
but the relationship between carbon dioxide fluxes and other parameter was very
different within each season and impound period. So the results above will
provide more supports for understanding the import pathway and transfer of
aquatic carbon cycle caused by large river interception project in China.
PMID- 29965566
TI - [Seasonal Pollution Characteristics and Source Identification of Polycyclic
Aromatic Hydrocarbons and Organochlorine Pesticides in Surface Water of
Baiyangdian Lake].
AB - Seasonal variations of 17 polycyclic aromatic hydrocarbons(PAHs) and 15
persistent organochlorine pesticides(OCPs) were analyzed during spring and summer
in surface water from 12 sampling sites of Baiyangdian lake to elucidate their
seasonal pollution characteristics and sources. The results showed that total
concentrations of PAHs in surface water of Baiyangdian lake ranged from 35.38 to
88.06 ng.L-1(46.57 ng.L-1 in average) in spring and 25.64 to 301.41 ng.L-1(76.23
ng.L-1 in average) in summer, respectively, and total concentrations of OCPs
ranged from 0.69 to 4.50 ng.L-1(1.77 ng.L-1 in average) in spring and 0.11 to
3.20 ng.L-1(0.90 ng.L-1 in average) in summer, respectively. Seasonal pollution
characteristics of PAHs in surface water during two different seasons showed that
the total concentration of PAHs was much higher in summer than in spring at three
sampling sites of Baiyangdian lake including Qiantang, Guancheng and Anxin
bridge, and the level of PAHs in spring was much higher than that in summer at
the other nine sites. While seasonal pollution characteristics of OCPs showed
that the total concentration of OCPs was much higher in summer than in spring in
samples of Guancheng sites, and the level of OCPs in spring was slightly higher
than that in summer in the rest of samples. From the perspective of spatial and
temporal variations in the composition patterns of PAHs and OCPs in surface water
of Baiyangdian lake, PAHs were predominated by 3-ring PAHs with 45.92% and
61.36%(52.60% in average) of total PAHs in spring, while in summer Nap was the
chief component of 2-ring PAHs in three sampling sites including Qiantang,
Guancheng and Anxin bridge with 84.91%, 91.04% and 78.10% of the total,
respectively, and 3-ring PAHs were primary pollutants in the other nine sites
with 37.14% to 53.90%(48.94% in average) of the total. Residues of HCHs and DDTs
were detected in different degrees and beta-HCH was the main pollutant at all
sampling sites with 29.94% and 100%(59.87% in average) of total HCHs in spring,
while beta-HCH was the predominant compounds at five sampling sites with 57.55%
and 80.23%(61.98% in average) in summer and alpha-HCHs and delta-HCH were
abundant at other sampling sites. Source analysis based on isomer ratios
indicated that the main source of PAHs in Baiyangdian lake originated from
combustion sources, and additional sources for several sampling sites could be
petroleum processes. Ratios of HCH isomers and DDT congeners confirmed that
environmental historical residues and long range atmospheric transport were the
major sources of OCPs contamination in the study area. Compared with the water
quality standard of China and other countries or organizations, concentrations of
PAHs and OCPs in surface water of Baiyangdian lake did not exceed the target
values of the standard. However, the concentrations of alpha-HCH and p,p'-DDD in
Anxin bridge and Quantou sites exceeded the limit of human health ambient water
quality criteria developed by EPA, which reflected that alpha-HCH and p,p'-DDD
would have a potential hazards risk to the residents from Baiyangdian district.
PMID- 29965567
TI - [Distributions, Sources and Pollution Assessment of Hg in Sediment of Douhe
Reservoir in Tangshan City].
AB - Sediment cores from Douhe reservoir in Tangshan City were sampled in August 2013,
in order to evaluate the mercury (Hg) pollution degree and its possible sources.
Agriculture soils surrounding the Douhe reservoir and sediments from an upstream
reservoir (Daheiting) were also collected. Total mercury (THg), methylmercury
(MeHg), dissolved mercury in pore water (DHg) and organic matter (OM) in sediment
of Douhe reservoir were analyzed, while, only THg in the agriculture soils and
upstream reservoir sediments was determined. Finally, the geoaccumulation index
method was applied to evaluate the Hg pollution status in soils and reservoir
sediments. The results showed that THg content in sediment of Douhe reservoir
ranged from 19 to 97 ng.g-1. dw, MeHg (dw) from 0.02 to 1.27 ng.g-1, and the
contents of both THg and MeHg were higher in the upper layers than the deeper
layers, indicating that Hg in sediments was increasing in recent years by the
exogenetic loadings. THg (dw) in soils offshore the Douhe reservoir, which is
close to a large coal-fired power plant, averaged at 22 ng.g-1. Among the three
sediment cores of Douhe reservoir, the central point had the highest THg,
followed by the western site, and the eastern site had the lowest THg. While, THg
content (dw) in sediments of Daheiting reservoir was much higher, with a mean of
176 ng.g-1. Combining all the above information, we concluded that Hg in Douhe
reservoir was mainly derived from the Daheiting reservoir and the mercury
atmospheric deposition from the nearby coal-fired power plant contributed a less
content. THg and MeHg in the sediments of Douhe reservoir were positively
correlated with OM, indicating that OM in sediments had good ability of adsorbing
THg and MeHg, and also played an important role in Hg methylation. The
geoaccumulation index (Igeo) showed that the Hg pollution status deceased in this
order:central of Daheting, Daba of Daheting, central of Douhe, western of Douhe,
eastern of Douhe, soils surrounding Douhe. Central and western sites in Douhe
belonged to moderate pollution and the eastern site belonged to slight pollution.
While, sediments of Daheiting reservoir, affected by the iron ore mining
activities, were in the moderate and strong pollution status.
PMID- 29965568
TI - [Release Characteristics of Mercury from Submersed Typical Herbaceous Plants in
the Water-Level Fluctuation Zone of the Three Gorges Reservoir Area].
AB - In suit inundation experiments of three typical herbaceous plants were conducted
in field to investigate the mercury release characteristics of plants grown in
the water-level fluctuation zone of the Three Gorges Reservoir after flooding by
regulating the water level. To realize this objective, this study mainly focused
on the dynamic change of total mercury (THg) concentrations in plants after
inundation, the release rate and flux of THg from plants and its release load in
this region. The results showed that the release process of THg in plants fitted
exponential curve, suggesting that mercury release rate was quick in the initial
inundation period and then flat afterwards as the decomposing plants. The THg
release amounts (followed the order of Alternanthera philoxeroides > Polygonum
lapathifolium > Cynodon dactylon) were probably influenced by initial C/N ratio
and THg concentrations of plants. The decrement of THg concentrations in per unit
mass of plants residue was found to be generally proportional to their initial
C/N ratio, while the THg release amounts were generally proportional to the
initial THg concentrations of plants. The total release loads of three plants
(Alternanthera philoxeroides, Polygonum lapathifolium, Cynodon dactylon) were
estimated to be 167.31, 78.13 and 88.33 mg.hm-2, respectively, according to their
weight distribution and biomass in the water-level fluctuation zone of the Three
Gorges Reservoir Area.
PMID- 29965569
TI - [Distribution Characteristics and Health Risk Assessment of Heavy Metals in
Surface Water Around Electroplating Factories].
AB - To investigate the distribution characteristics and the human health risks of
heavy metals in surface water samples, 30 samples were collected around
electroplating factories of Machong, Shatian, Humen, Changan and Dalingshan towns
in Dongguan city, 8 heavy metals(As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) contents were
measured and analyzed by using multivariate statistical analysis method and human
health risk assessment model. The results showed that the maximum concentrations
of Cr, Pb and the average concentration of Hg exceeded Environmental Quality
Standards for Surface Water(GB 3838-2002, Grade III), the concentrations of Cr,
Cu, Hg, Ni, Zn and Pb during rainy season were all higher than that those during
dry season. Multivariate statistical analysis indicated that Cd, Cr, Cu, Ni and
Zn mainly originated from the contaminated electroplating factories, Pb and Hg
were mainly affected by the traffic sources, and As was significantly correlated
with natural sources. Health risk assessment result of surface water indicated
that heavy metal pollution would lead to high health risks especially for
children, and the health risks of heavy metals through drinking pathway were 2-3
orders of magnitude higher than the values caused by dermal contact pathway.
Moreover, carcinogenic risks caused by Cr and As were higher than the maximum
allowance levels (5*10-5 a-1), and non-carcinogenic risks of the heavy metals (10
10-10-7 a-1) decreased in the order of Pb > Ni > Cu > Hg > Zn, which were 4-5
orders of magnitude lower than the maximum allowance levels.
PMID- 29965570
TI - [Speciation and Ecological Risk of Heavy Metals in Surface Sediments from Jiulong
River].
AB - Speciation characteristics of fifteen heavy metals in seventeen surface sediments
from Jiulong River was analyzed using the modified BCR protocol and dilute HNO3
method, respectively. The results of the modified BCR protocol showed that most
of the elements (Fe, Ni, V, Tl, Ba, Sb, Ga, Cr and Sr) existed mainly in residual
fractions, and extractable fraction was dominant for Mn (83.8%), followed by Cd,
Pb, Zn, Co and Cu (80.0%, 75.5%, 74.3%, 70.8% and 57.7%). The results of dilute
HNO3 method showed that the proportions of the dilute HNO3-extractable fractions
of Pb, Mn, Cd, Co, Zn and Cu were higher (70.4%, 65.4%, 58.7%, 48.4%, 44.5% and
45.5%). The assessment results of RSP (ratio of secondary phase to primary phase)
indicated that Pb, Mn, Cd, Co, Zn and Cu in surface sediments of Jiulong River
had higher ecological risks. Both extraction methods had merits and demerits
respectively. In general, the dilute HNO3 method is enough to analyze the
bioavailability and ecological risk of heavy metals in sediments.
PMID- 29965571
TI - [Fractionation and Contamination Assessment of Metal Elements in the Surface
Sediments of Yundang Lagoon in Xiamen].
AB - Total concentrations of 15 metal elements in the surface sediments of Yundang
Lagoon in Xiamen were determined using ICP-MS. The fractions were extracted by a
modified BCR method. The results indicated that in different areas of Yundang
Lagoon, the order of the concentrations of Cd, Cu, Sr, Pb, Zn and U was:outer
lagoon > ditch > inner lagoon, the order for Cr, Co, Ni, V, Fe, Li, Rb and Mn
was:inner lake > outer lake > ditch. Cu, Zn and Pb were mainly in the reducible
phase; Cd was mainly in the acid soluble-extractable and reducible phases; Co,
Ni, U, Fe and Mn were mainly in the reducible and residual phases; Li, V, Cr, Rb
and Ba were dominated by residual phase. The potential ecological risk of metal
elements suggested that V, Cr, Co, Ni, Zn, Cu, Cd and Pb were at a low potential
ecological risk level. The results of ratio of secondary phase to primary phase
(RSP) assessment indicated that Cu, Cd and Zn showed high pollution level; Pb
showed moderate pollution level; Co, Mn, Sr and U were in a low polluted
condition; Ni, Fe, Cr, V, Li, Ba and Rb showed no pollution. In general, Yundang
Lagoon was in a low potential ecological risk.
PMID- 29965572
TI - [Source Analysis, Spatial Distribution and Pollution Assessment of Heavy Metals
in Sewage Irrigation Area Farmland Soils of Longkou City].
AB - Farmland soils in sewage irrigation area at Longkou City were collected, soil pH
together with the heavy metal content were tested. Taking 70 soil points as the
study object, this paper investigated the source of heavy metals in this area
based on the correlation analysis and PCA of multivariate statistical analysis
theory. We studied the spatial variation and distribution characteristics about
heavy metals using both the theory of geostatistics and GIS spatial interpolation
method. At last, the heavy metal pollution was evaluated in the way of Nemerow
Index and improved fuzzy evaluation method. It turned out that, 9 kinds of heavy
metal elements in the soil of research area had a certain degree of enrichment,
among them the average of Cd was 3.06 times as high as the background value, and
its enrichment was most severe. The result of Nemerow Index showed that, the
values of comprehensive pollution index of Cu, Cd and Pb respectively were 7.06,
6.10 and 5.54, and they all belonged to high levels of pollution. According to
the results of correlation analysis and principal component analysis, Cu, Zn
together with Pb, Cd were mainly affected by human factors, sewage irrigation was
their common pollution factor, the pollution sources for the first two heavy
metals included excessive use of chemical fertilizers and pesticides in
agricultural production and the accumulation of long time, whereas pollution from
northern coal mining and coal gangue piled up as well as plating, machinery
manufacturing and other industrial pollution were the pollution sources of the
latter two elements. Other elements (Co, Cr, Mn, Ni and As) were mainly
influenced by natural factors such as parent material. Comprehensive evaluation
results showed that, among the 70 points, 13 points had moderate pollution,23
points belonged to light pollution, 28 points were at alert level, 6 points were
in the safe range. From the perspective of spatial distribution,high value areas
of heavy metal contents were mainly concentrated in towns of Zhuyouguan and Xufu.
This showed that, sewage irrigation caused a certain degree of heavy metal
pollution to local soil.
PMID- 29965573
TI - [Efficiency and Mechanism of Purifying High Iron-Manganese from Ground Water in
the Cold Villages and Towns Based on The Coupling of Rice Husk and Iron-Manganese
Oxidizing Bacteria].
AB - Aiming at the special geo-climatic conditions and typical problems constraining
the development of villages and towns, making villages and towns have the
following characteristics:green and low-carbon, energy saving and environmental
friendly, the coupling process of adsorption by carbonized rice husk particles
and biological oxidation using Bacillus megaterium bacteria was developed for
purifying high iron-manganese from groundwater in the cold villages and towns.
The quick start-up method of biological filter at low temperature was studied.
Based on the contact oxidation and biological method, iron removal efficiency and
reaction rate in different filtration layers under different filtration
conditions were comparatively analyzed, and iron removal mechanism of biological
filter was determined. Filter materials and the solid samples in backwash water
at different stages were characterized and the manganese removal mechanism of
biological filter was analyzed through SEM, FTIR, XPS, Raman spectra and EPR. The
results showed that the active biological membrane reached mature and stable only
after 15 d with the operation mode of bacteria liquid cycle and low filtration
rate in the filter column. The effluent concentration met the requirements of
drinking water quality (GB 5749-2006) in the stable operation process. Fe, Mn and
bacteria were lower than 0.3 mg.L-1, 0.1 mg.L-1, 100 CFU.mL-1, respectively. Iron
removal mechanism relied mainly on the physical and chemical effects,
supplemented by biological function. During the biofilm culturing stage and
initial stable operation stage of filter column, manganese removal relied mainly
on the biological effect. The physical chemistry was preferred at later stable
operation stage. The study provides technical support for the applications of
treating collectively Fe2+ and Mn2+ in groundwater.
PMID- 29965574
TI - [Peroxidation of High Algae-laden Water by Ozone: Algae Organic Matter
Transformation and Disinfection By-products Formation].
AB - Formation characteristics and transferring feature of nitrogenous/carbonaceous
disinfection by-products have been observed under different ozone dosages and pH
conditions, and essential nature conversion of Algae organic matters has been
also studied concurrently, based on high algae-laden water. The results showed as
follows:reduction of Microcystis aeruginosa could reach 36% at the ozonation
concentration of 28.92 mg.L-1. Humic acid-like compounds first increased and then
decreased with continuing addition of ozone dosage, whereas soluble microbial
products, fulvic acids and aromatic protein substance all diminished. Low dosage
of ozone had certain effect on control of dichloroacetonitrile(DCAN) and
trichloroacetonitrile (TCAN) formation potential, yet augmented the yield of
trichloronitromethane (TCNM) and 1,1,1-trichloroacetone(1,1,1-TCP) precursors,
and N-DBPs formation potential was promoted with the increase of ozone dosage.
Algae removal efficiency was relatively the best under the acidic condition,
meanwhile, UV254 and DOC increased with the rise of pH, though the change was not
outstanding. Humic acid-like compounds decreased with the rise of pH; ozonation
could degrade the soluble microbial products and the consequence was affected
little by the change of pH. DCAN and TCAN formation potential decreased with the
rise of pH; TCNM formation potential appeared to be the highest when the pH was
10, whereas the highest 1,1,1-TCP formation potential was found at pH 7.
PMID- 29965575
TI - [Effects of Pretreatment on Hydraulic Irreversible Membrane Fouling During
Ultrafiltration Short Process: A Pilot Study].
AB - Pilot-scale performances for ultrafiltration of Dongjiang river water without and
with micro-coagulation and coagulation-adsorption-sedimentation pretreatments
were conducted to investigate the effects of pretreatments on hydraulic
irreversible fouling of ultrafiltration short processes. Scanning electron
microscope (SEM) imaging, high performance size exclusion chromatography (HPSEC)
and fluorescence excitation-emission matrix (EEM) were employed to identify
foulants responsible for irreversible fouling during ultrafiltration with and
without pretreatments. The results showed that the hydraulic irreversible fouling
rate was 0.16 kPa.d-1 with micro-coagulation pretreatment at 10 L.(m2.h)-1, while
the rate without pretreatment was 0.32 kPa.d-1 at the same flux. Meanwhile, the
fouling rate with coagulation-adsorption-sedimentation pretreatment was almost
zero at the same flux. Furthermore, when the flux increased to 17 L.(m2.h)-1, the
irreversible fouling was not observable with coagulation-adsorption-sedimentation
pretreatment (backwashing every 24 hours). Properties of foulants from external
membrane and internal membrane after backwashing showed that the protein-like and
fulvic-like substances were responsible for irreversible fouling in Dongjiang
river water. Furthermore, structural alteration of cake layer resulted in less
cake resistance and higher backwash efficiency after micro-coagulation
pretreatment, leading to less irreversible fouling. Coagulation-adsorption
sedimentation pretreatment decreased irreversible fouling with higher removal
efficiency of protein-like and fulvic substances, which were the foulants
responsible for irreversible fouling during ultrafiltration. Both micro
coagulation and coagulation-adsorption-sedimentation pretreatments decreased
irreversible fouling during ultrafiltration short process.
PMID- 29965576
TI - [Fenton-like Catalytic Removal of Organic Pollutants in Water by Framework Cu in
Cu-Al2O3].
AB - To address the problem of low activity for Fe-based Fenton-like catalysts at
neutral pH, Cu-Al2O3 Fenton-like catalyst was prepared by a simple co
precipitation method. The samples were characterized by means of X-ray
diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and diffuse reflectance
UV-vis spectra (UV-vis DRS). The results showed that both Cu2+ and Cu+mainly
existed in the bulk framework of Al2O3 for Cu-Al2O3 with appropriate Cu doping
(lower than 4.77% Cu), forming the bond of Al-O-Cu, while excessive Cu doping in
Al2O3 (e. g. 7.58% Cu) could result in the occurrence of extraframework Cu
species. The Fenton-like catalytic performance of the prepared samples was
evaluated by the degradation of 2-chlorophenol (2-CP) and Rhodamine B (RhB). The
results showed that the catalyst with framework Cu species had high catalytic
activity and stability for the degradation of 2-CP and RhB. After reaction for 2
h, the degradation rate of 2-CP reached up to 54% over Cu-Al2O3(4.77% Cu) in the
presence of H2O2, the corresponding TOC removal reached 49%, and the Cu release
concentration was only 0.0255 mg.L-1. However, the existence of extraframework Cu
in Al2O3 would lead to the reduction of the catalytic performance. ESR analysis
showed that.OH and HO2-/O2-. were the primary active species.
PMID- 29965577
TI - [Oxidation Destruction of Cu(CN)32- by Persulfate].
AB - In recent years, cyanide contamination problem is becoming more and more serious.
Cyanides widely occur in the wastewater from metallurgical industry and
electroplating industry. The efficiency for cyanides removal of conventional
physical and chemical methods is not very satisfactory. Therefore, it is urgent
to develop highly efficient and environmental friendly methods for the removal of
cyanides. As an environmental-friendly oxidant, potassium persulfate is widely
used in the treatment of organic pollutants. The destruction of Cu(CN)32- was
investigated by homogeneous K2S2O8 under alkaline conditions, and the reaction
mechanism was analyzed. The effects of the amount of K2S2O8 and the ratio of
Cu+/CN- on the degradation of CN- were studied. With the increase of K2S2O8 dose,
the rate of CN-oxidation was accelerated. The removal efficiency of CN- reached
89.6% after 60 min of reaction in the presence of 2 mmol.L-1 K2S2O8. Oxidation of
CN- was accelerated with Cu+/CN- increasing from 2.0 to 5.0. Cu+ was oxidized to
Cu2+ and copper oxide was formed during the reaction. The reactive radicals were
analyzed using electron spin resonance and radical quenching experiments, and the
results indicated that both radicals oxidation pathway and non-radical oxidation
pathway were responsible for the removal of Cu(CN)32- by K2S2O8.
PMID- 29965578
TI - [Enhanced Removal of Herbicide 2,4-dichlorophenoxyacetic Acid and Simultaneous
Power Generation in Microbial Fuel Cells].
AB - This study investigated the effects of a widely used herbicide 2,4
dichlorophenoxyacetic acid on power generation, pollutants removal from microbial
fuel cells (MFCs) and microbial community changes, and also explored anode pre
aeration for enhanced 2,4-D removal and power generation. The results showed that
when 2,4-D was inputted to the anode chamber of MFCs which was previously
enriched with acetate sodium as the fuel, the voltage output and power density
declined and the internal resistance increased apparently. The maximum power
density declined to 0.057 W.m-2 in the presence of 300 mg.L-1 2,4-D comparing to
0.151 W.m-2 obtained with acetate alone (850 mg.L-1), and the internal resistance
increased from 524 Omega to 1230 Omega correspondingly. To accelerate 2,4-D
removal rate and reduce its inhibition to anode exoelectrogens, 6h pre-aeration
was applied to the anode chamber. Fast removal of 2,4-D was achieved during
aeration period and simultaneous high maximum voltage output (0.42-0.47 V) was
obtained. Anode microbial community changed after 2,4-D addition and several 2,4
D degrading bacteria and 2,4-D tolerant exoelectrogen were enriched. MFCs could
be used for 2,4-D removal and simultaneous power generation through anode pre
aeration.
PMID- 29965579
TI - [Adsorption Characteristics of Copper in Water by the Porous Biomorph-Genetic
Composite of HAP/C with Eucalyptus Wood Template].
AB - The specific characteristics and mechanism of adsorption of Cu(II) were studied
by using HAP/C composite (PBGC-HAP/C) as adsorbent, and using pH value of the
solution system, initial concentration of Cu(II) and particle size of the
material as influential factors. The results showed that when the solution was
weak acid (pH=5), the adsorption effect was the best; the increase of the initial
concentration of the reaction system was not conducive to the enhancement of the
adsorption effect; and the decrease of the particle size of the adsorbent
facilitated the adsorption process. The pseudo-second-order kinetic model could
accurately describe the adsorption process, and the calculated adsorption
capacity(0.99, 1.93, 4.03 mg.g-1)was close to the experimental measured
values(0.99, 1.93, 4.05mg.g-1); Langmuir model could fit the adsorption process
very well, which indicated that adsorption was monolayer adsorption and the
increase of temperature was conducive to adsorption. The thermodynamics test
results of DeltaGtheta<0, DeltaStheta>0 and DeltaHtheta>0 showed that the
adsorption process was endothermic and spontaneous. Through comparative analysis
of the SEM, EDS, XRD and FTIR of materials before and after adsorption, the
results indicated that the chemical complexation reaction of Cu(II) with the
oxygen functional groups on the surface of PBGC-HAP/C was the main purification
mechanism, which was accompanied with physical adsorption, electrostatic
adsorption and ion exchange.
PMID- 29965580
TI - [Biological Toxicity Evaluation of Domestic Wastewater Based on A2/O Treatment
Processes Using a Battery of Bioassays].
AB - In order to accurately evaluate the comprehensive ecotoxicity of domestic
wastewater and the toxicity reduction efficiency of different treatment
processes, standardized assays focusing on Vibrio fischeri, SOS/umu test and
yeast estrogen screen were applied. Simultaneously, male zebrafish was used to
address the mode of action of endocrine disrupting effects of wastewater and
reclaim water on aquatic life. Results of this study indicated that the influent
was severely polluted:highly acute toxicity, genotoxicity and estrogenicity were
observed. After the secondary biological treatment, the above toxicities were
significantly reduced, making the water quality improved. However, the
estrogencity of secondary effluent was detected at 1.89 ng.L-1, which still posed
potential risk on the aquatic life in receiving water. In addition, the up
regulation of estrogen receptor (esr 1) and vitellogenin (vtg 1) in the livers of
zebrafish was observed after exposure to 2.5 times concentrated wastewaters,
which demonstrated that wastewater modulates hormonal activities of aquatic life
by disturbing target genes expression. Moreover, the slight down-regulation of
esr 1 was observed in the gonads. These observations reflect that the evaluation
of biological toxic effect should be analyzed in different tissues or organs, so
that more comprehensive information about the adverse effects of wastewaters on
aquatic life can be obtained.
PMID- 29965581
TI - [Effect of Wastewater Nitrogen Concentrations on Nitrogen Removal Ability of
Myriophyllum aquaticum].
AB - Myriophyllum aquaticum, which is an important plant for constructed wetlands, has
powerful purification ability for wastewater, however, the relationship between
nitrogen removal ability of Myriophyllum aquaticum and wastewater nitrogen
concentrations is still unclear. In this study, pot culture experiment was
conducted to investigate the effect of wastewater nitrogen levels on nitrogen
removal ability of Myriophyllum aquaticum. 7 nitrogen levels were set up as
following:2, 5, 10, 20, 100, 200, 400 mg.L-1. The results showed that when the
wastewater nitrogen concentration was not higher than 20 mg.L-1, Myriophyllum
aquaticum with 20 mg.L-1 of nitrogen concentration grew best in the first 3
weeks; the removal rates of total and ammonia nitrogen were nearly 100% after one
week, while the nitrate nitrogen concentrations were very low and varied little;
the nitrogen contents of Myriophyllum aquaticum had no significant change, the
upper part nitrogen content was higher than the underneath, Myriophyllum
aquaticum could also remove nitrogen from the sediment. When wastewater nitrogen
concentrations were 100-400 mg.L-1, Myriophyllum aquaticum with 200 mg.L-1 of
nitrogen concentration grew best from 4th to 5th week; the removal rates of total
nitrogen were 76.5%, 71.5% and 48.1% in the three treatments, and the removal
rates of ammonia nitrogen were 99.6%, 99.3% and 60.2% respectively, while the
removal rates of nitrate nitrogen were all about 50% and there was no significant
difference among treatments; the nitrogen contents of Myriophyllum aquaticum
increased with nitrogen levels, but the difference between upper part and
underneath was not remarkable, showing uniform distribution; nitrogen
accumulations by Myriophyllum aquaticum and sediment accounted for 27.9%-48.4%
and 12.2%-24.4% of total nitrogen loss in wastewater. Therefore, the nitrogen
removal ability of Myriophyllum aquaticum should be inhibited by higher
wastewater nitrogen level, the ammonia nitrogen removal rate was significantly
higher than nitrate, the mechanism of Myriophyllum aquaticum nitrogen
accumulation and distribution should also be affected by wastewater nitrogen
level, and further research is needed.
PMID- 29965582
TI - [Recovery Performance of ANAMMOX Process after Inhibition Resulting from
Seawater].
AB - An anaerobic sequencing batch reactor (ASBR) was operated to investigate the
recovery performance of ANAMMOX reactor after the inhibition of 100% seawater
concentration. The results showed that the nitrogen removal performance of
ANAMMOX reactor suffered inhibition of high salinity concentration. However, it
could enter a period of stable nitrogen removal efficiency again after an interim
stable period and a recovery period. The nitrogen removal rate (NRR) could reach
0.52 kg.(m3.d)-1, which was similar to the control group, containing 10% seawater
and having a NRR of 0.462 kg.(m3.d)-1. The modified Logistic model and modified
Gompertz model were revised and their application field was broadened. The re
modified Logistic model was suggested to be used to simulate the NRR recovery
process of ANAMMOX reactor that suffered inhibition of 100% seawater
concentration. The doubling time of NRR was calculated to be 11.359 d using the
prediction formula established for the recovery time of NRR.
PMID- 29965583
TI - [Impact of Starvation Conditions on Biological Community Structure in Sulfur
Autotrophic Denitrification Reactor].
AB - Sulfur/dolomite and pyrite/dolomite autotrophic denitrification reactors were
applied to treat the secondary effluent of wastewater treatment plant to explore
the removal effect, the changes of microbial community, and recovery time of
reactors after starvation period. It was shown in the results that after 30 d non
water starvation endurance, the effluent concentrations of NO3--N in
sulfur/dolomite and pyrite/dolomite reactors increased from 1.78 mg.L-1, 11.32
mg.L-1 to 27.87 mg.L-1, 26.56 mg.L-1 respectively at the low temperature of 12
14C. In addition, sulfur/dolomite and pyrite/dolomite reactors recovered within 5
d and 11 d since restarted and could maintain a good effect of nitrogen removal
at low temperature. MiSeq high throughput sequencing results showed that the
abundance and diversity of the bacterial communities in starvation period in both
reactors were lower than those in recovery period. The dominating phylum was
Proteobacteria in both reactors while the dominating class was beta
Proteobacteria. Thiobacillus was identified as the main genus for denitrification
in sulfur/dolomite reactor.
PMID- 29965584
TI - [Quick Start-up of Anaerobic Ammonium Oxidation Process].
AB - In order to study the quick start-up process of anaerobic ammonium oxidation
(ANAMMOX), two types of reactors with different hydraclic flow state inoculated
with aerobic nitrifying sludge were investigated, the membrane bioreactor (MBR)
and anaerobic baffled reactor (ABR), respectively. The result showed that both
reactors successfully started up ANAMMOX process. The start-up period of the MBR
(90 d) was 20% shorter than the ABR (111 d). During the stable operation, the
average nitrogen (NH4+-N+NO2--N) removal capacity of 0.098 kg.(m3.d)-1 in the MBR
was also higher than that of 0.089 kg.(m3.d)-1 in the ABR. In addition, the
differences of sludge morphology were obvious in the two reactors; flocculent
sludge was developed in the MBR while ANAMMOX granular sludge was mainly formed
in the first compartment of the ABR. Moreover, the quantitative relationship
analysis between NH4+-N, NO2--N and NO3--N showed that the MBR system contained
more kinds of bacteria with nitrogen removal function, compared to the ABR, and
it was therefore more conducive to the removal of nitrogen. MBR exhibited a more
excellent performance for ANAMMOX start-up.
PMID- 29965585
TI - [A New Model for the Treatment of Low Ammonia Nitrogen Wastewater by CANON
Process].
AB - Automatic aeration and recirculation of effluent were used to start CANON process
with up flow sludge bed reactor, and the start-up and operation characteristics
of the process were studied. The results showed that the CANON process could be
started quickly and stably by the method of reoxygenation reflux under the
conditions of sludge volume fraction 25%, NH4+-N 157 mg.L-1, HRT 2 h. After 50
days of operation, the total nitrogen removal rate increased from 1.31 kg.(m3.d)
1 to 1.47 kg.(m3.d)-1; the reoxygenation reflux manner could effectively control
the amount of dissolved oxygen in the reactor, resulting in DO<0.01 mg.L-1, which
had a good inhibitory effect on the NOB in the system, and meanwhile provided a
good growth environment for AnAOB; By controlling the reflux flow, the production
rate of NO2- could be precisely controlled, reaching a good balance with NO2-
consumption rates, and thus avoiding the accumulation of NO2- and occurrence of
nitration reactions. Therefore, reoxygenation reflux CANON process showed a great
advantage in the operation stability, which provided a new model for the start-up
and stable operation of CANON process.
PMID- 29965586
TI - [Effects of Side-stream Phosphorus Recovery on the Performance of EBPR System
Under Low Dissolved Oxygen Condition].
AB - A sequencing batch reactor (SBR) was operated with alternating anaerobic/oxic
(An/O) condition to investigate the nitrogen and phosphorus removal performance
of EBPR with DO=1 mg.L-1 and the phosphorus recovery effect at extracting side
stream ratio of 0, 1/4, 1/3, 1/2 anaerobic phosphorus supernatant. The removal
efficiency of NH4+-N was found to be relatively stable during all experimental
stages but effluent COD of the system during later period remained as high as
81.3 mg.L-1. In the absence of side stream, the average phosphorus removal
efficiency was 89.4% and increased to 98.5% and 99.0% when the side stream ratio
was 1/4 and 1/3, respectively. However, the phosphorus removal performance began
to fluctuate with side stream ratio of 1/2 and the lowest phosphorus removal rate
was 65.4%. During each experimental stage, only one day effluent TP failed to
meet the national wastewater discharge standard A with side stream ratio of 1/3
in the initial period. Besides, 93.3% of effluent TP which could meet the
national standard with side stream ratio of 1/3 was far better than 45.5% of that
with side stream ratio of 1/2. Nevertheless, the phosphorus recovery rate
improved with the increase of side stream ratio. It was also observed that the TN
removal rate dramatically decreased to 50.9% when the side stream ratio increased
to 1/2. Consequently, a side stream ratio of 1/3 was found to be the optimal
condition in the whole experimental stage, and EBPR system under low dissolved
oxygen condition combined with phosphorus recovery through extracting side stream
could greatly improve the economic and environmental benefits.
PMID- 29965587
TI - [Identification and Influence of Quorum Sensing on Anaerobic Ammonium Oxidation
Process].
AB - Anaerobic ammonium oxidation (ANAMMOX), an innovative nitrogen removal
technology, has good prospects for applications. However, ANAMMOX bacteria grow
slowly and are hardly accumulated in bioreactors. In this study, a UASB reactor
inoculated with sludge from landfill leachate treatment plant was used for the
start-up of ANAMMOX process. Besides, exogenous quorum sensing signals (DSF and
AHL) were added to improve the adhesion of ANAMMOX sludge. The results showed
that the UASB successfully started the ANAMMOX process within 150 days of
operation. The total nitrogen removal rate reached 80% and the proportion of
ANAMMOX bacteria rose to 20%. There was a low concentration of AHLs signal
molecules in the ANAMMOX sludge. If the beta-position substituent group of AHL
added was a carbonyl group (including 3-oxo-C6-HSL, 3-oxo-C8-HSL, 3-oxo-C10-HSL
and 3-oxo-C12-HSL), the adhesion growth ability of the ANAMMOX sludge could be
improved. In the case of dosing with AHL molecules without beta-position
substituent groups, only C6-HSL and C12-HSL could promote the adhesion of ANAMMOX
sludge. The additions of C8-HSL, C10-HSL and DSF all had negative effects on the
adhesion of ANAMMOX sludge.
PMID- 29965588
TI - [Effects of Organic Loading Rate on Startup Performance of Anaerobic Digestion
with Vinegar Residues].
AB - Biochemical methane potential experiments were conducted to investigate the
effects of organic loading rate on the performance of anaerobic digesters with
vinegar residues. According to the comparisons of methane production and liquid
phase compositions, as well as thermogravimetry, X-ray Diffraction and infrared
spectroscopy analyses, the conclusions could be drawn that:1Lower organic loading
rate was better to mitigate the accumulation of VFAs and pH decrease during the
hydrolysis and acidification of organic matters, which consequently improved
methane production. When the inoculum to substrate ratio was 1:1[organic loading
rate of 1.78 g.(L.d)-1, pH=7.60], the cumulative methane production was the
highest, reaching 2249.7 mL, and the performance of the digesters was stable. The
VFAs content increased with the increase of the organic loading rate, leading to
the suppression and further the stop of methane production. And when the inoculum
to substrate ratio was 1:4[organic loading rate of 7.12 g.(L.d)-1, pH=5.52], the
simultaneous generation of acetate and lactic acids could be achieved at 8000
mg.L-1 and 2650 mg.L-1, respectively. 2 As vinegar residues were short-range
ordered with microcrystalline structure or mainly contained amorphous substances,
they were more biodegradable than feedstocks such as corn stalk. During the
anaerobic digestion processes, the degradation rates of lignin, cellulose and
hemicellulose increased with the decrease of organic loading rate.
PMID- 29965589
TI - [Influencing Mechanism of Calcium Peroxide Pre-treatment on Dewatering
Performance of Waste Activated Sludge].
AB - The evolution of sludge filteration dewaterability, floc structure and hydrolytic
kinetics with calcium peroxide oxidation pre-treatment was investigated in this
study. The effect of sludge characteristics with combined process of ferrous ion
and calcium peroxide was deeply analyzed and the result suggested that the sludge
dewatering performance was improved first and then worsened after CaO2 addition.
When the dosage was 20 mg.g-1, sludge reached its optimal dewaterability. At the
same time, sludge was effectively dissolved and the floc structure became loose
and broken with the increase of organic matters in the supernatant. Moreover,
sludge solubilization process followed the pseudo-zero-order kinetic equation
well and the reaction rate of sludge with CaO2 treatment was 15.2 mg.L-1.h-1. In
addition, sludge floc lysis was enhanced by the treatment of ferrous ion and
calcium peroxide oxidation, whilst sludge dewaterability was improved due to the
reconstruction of sludge floc structure by the iron ions produced. This study
provided theoretical basis for application of calcium peroxide pre-treatment and
its combining technique in sludge treatment.
PMID- 29965590
TI - [Treatment Effects of Earthworm Constructed Wetlands in Different Working
Conditions].
AB - The feasibility of a new sludge treatment technology of earthworm constructed
wetlands was tested by adding earthworm into the traditional sludge dying reed
beds. The dewatering and stabilization effects of the upper layer sludge were
tested under different sludge loading rates of 48, 65, 80 kg.(m2.a)-1, different
earthworm stocking densities of 0, 0.43, 0.54, 0.65 kg.m-2 and different sludge
loading frequencies. The results indicated that it was feasible to provide a
shelter for earthworm during the loading period by setting a damper with a buried
depth of 10 mm. The addition of earthworm could effectively improve the
dewatering and stabilization effects of earthworm constructed wetlands, by
lowering the DHA and decreasing the moisture content and VS of sludge by 15% and
10% respectively. The stabilization effects of earthworm constructed wetlands
reached the best under the stocking density of 0.65 kg.m-2. With the increase of
sludge loading rate and decrease of loading frequency, the running efficiency of
earthworm constructed wetlands would be worse.
PMID- 29965591
TI - [Effect of PFOA on Oxidative Stress and Membrane Damage of Escherichia coli].
AB - Perfluorooctanoic acid (PFOA) is widely used in industrial production because of
its strong chemical stabilities and good hydrophobic and oleophobic properties.
It was considered to be a widespread persistent organic pollutant in environment
in recent years. The oxidative stress and membrane damage of Escherichia coli
exposed to PFOA were measured by flow cytometry (FCM) and the toxic mechanism of
PFOA was also preliminarily explored. The results showed that, under the stress
of PFOA, the intracellular reactive oxygen species (ROS) content of E. coli
increased, the unsaturation degree of fatty acid decreased, the malondialdehyde
(MDA) content increased, the membrane permeability increased, the membrane
potential decreased, and the activities of Na+K+-ATPase and Ca2+Mg2+-ATPase
showed a compensatory increase first and then decreased. Therefore, owing to the
stress of PFOA, the higher intracellular ROS in E. coli reacted with membrane
unsaturated fatty acids by peroxidation,and then reduced cell membrane fatty acid
saturation, accumulated MDA in cells, and further caused damage to cell membrane,
reduced the ATPase activity, and eventually resulted in inactivation or apoptosis
of E. coli. This study provided more evidence for the further study on
environmental ecological toxicology of PFOA.
PMID- 29965592
TI - [Physicochemical Properties and Antibacterial Effect of Silver Nanoparticles: A
Comparison of Environmental and Laboratorial Conditions].
AB - This study aimed to understand how the physicochemical properties of silver
nanoparticles (AgNPs) affected its toxicity in the aquatic environment. The
morphologies of oleylamine-coated AgNPs (4 nm) under environmental and laboratory
water conditions were studied under transmission electron microscopy, and the
results showed oleylamine-coated AgNPs formed big aggregates in the environmental
water samples after 12 h equilibration. Dynamic light scattering results also
showed that oleylamine-coated AgNPs had larger hydrodynamic size in all water
samples as compared to its primary size (4 nm). Exposure to oleylamine-coated
AgNPs inhibited the growth of Bacillus subtilis (B. subtilis) and reduced its
cell viability in Luria-Bertani (LB) broth and 0.85% NaCl, respectively. A dose
dependent toxicity of AgNPs in B. subtilis was observed in laboratorial medium
conditions but not in environmental water condition. Low concentration of AgNPs
exhibited lower toxicity in environmental water samples as compared to that in
laboratorial medium conditions. Separating AgNPs from bacterial suspension
through a dialysis membrane enhanced the cell viability of B. subtilis
significantly. In the environmental water samples, the AgNPs-bacteria interaction
would be reduced with the formation of big aggregates by AgNPs, which
consequently decreased its toxicity in aquatic environment.
PMID- 29965593
TI - [Pollution Characteristics of Chlorobenzenes in Organs of Fish from Typical
Epidemic Areas of Schistosomiasis Prevalence].
AB - Sixty-eight fish samples were collected from typical epidemic areas of
schistosomiasis prevalence. The contents of 12 CB congeners in fish samples were
measured using GC/MS technique. The results indicated that 1,3-DIC, 1,4-DIC, 1,2
DIC and HCB were the most predominant CB congeners in the samples from the
studying area. The source of HCB was PCP (pentachlorophenol), which was used to
control the schistosomiasis prevalence, used in study area. And DIC came from the
degradation of HCB and the articles of daily use. The geometric average of CBs in
muscle ranged from 2731.50 to 7811.23 ng.g-1 lipid weight, while the summarized
concentration of CBs in fish gonads, brains, kidneys, livers ranged from 2557.89
to 4640.05 ng.g-1 lipid weight, 2423.18 to 3329.61 ng.g-1 lipid weight, 1628.05
to 4667.76 ng.g-1 lipid weight and 704.92 to 1086.96 ng.g-1 lipid weight,
respectively. When compared to other studies in China and other countries, the
concentrations of CBs in these fish samples were at a relatively high level.
PMID- 29965594
TI - [Effect of Nano Zeolite on Growth, Activity of Antioxidant Enzyme, and Chemical
Fractions and Concentration of Cd in Chinese Cabbage].
AB - Pot experiment was carried out to investigate the influence of nano zeolite (NZ)
and ordinary zeolite (OZ) on the growth, activities of antioxidant enzyme, Cd
fraction and Cd concentration in two varieties of Chinese cabbage. The results
showed that the activities of SOD, CAT and POD in the shoot and root of two
varieties increased, and the dry weight of shoot and the total dry weight of
Chinese cabbage increased by 4.5%-96.5% and 3.4%-88.4%, respectively. The
application of zeolite effectively reduced the Cd concentration of shoot and root
in the two varieties of Chinese cabbage, and the reduction range increased with
the increase of the application amount of zeolite. Under the low Cd condition
(1mg.kg-1 Cd), the Cd concentration of edible parts (shoots) in SD4 variety and
XJC3 variety decreased by 1.0%-75.0% and 19.5%-68.9% (except the Cd1+OZ5/OZ10
processing), respectively. Under the high Cd condition (5 mg.kg-1 Cd), the Cd
concentration of the edible parts (shoots) in SD4 variety and XJC3 variety
decreased by 7.2%-53.2%(except Cd5+OZ10 processing) and 0.7%-63.0%, respectively.
The Cd concentrations of the edible parts (shoots) in tow varieties of Chinese
cabbage in the nano zeolite treatments decreased by 10.5%-65.7% compared with the
ordinary zeolite treatments. In Cd contaminated soils (1 mg.kg-1 and 5 mg.kg-1
Cd),) the total extraction amount of Cd in the edible parts (shoots) of SD4
variety reduced by 12.4%-68.8% and 13.2%-55.6% (except of Cd5+OZ5 processing),
and the total extraction amount of Cd in the edible parts (shoots) of XJC3
variety reduced by 9.4%-71.5% and 3.1%-38.7% (except of Cd1+OZ5 processing),
respectively. The application amount of nano zeolite (NZ) and ordinary zeolite
(OZ) was more, the reduction range of the total extraction amount of Cd in the
edible parts (shoots) of two varieties of Chinese cabbage was greater.
PMID- 29965595
TI - [Effect of Different Iron Minerals on Bioaccessibility of Soil Arsenic Using in
vitro Methods].
AB - To explore the effects of different iron minerals on soil arsenic
bioaccessibility, ferrihydrite, goethite and hematite were used in PBET, SBRC and
IVG in-vitro experiments in this study. The relationship between arsenic
bioavailability in gastric, small intestinal phases and arsenic speciation was
also studied. The results showed that when 1% ferrihydrite was added, arsenic
bioavailability in gastric phase was 2.22%, 5.11% and 7.43% by PBET, SBRC and IVG
methods, respectively, while in the small intestinal phase it was 3.39%, 2.33%
and 6.18%. At an elevated ferrihydrite dosage of 2%, significant difference in
arsenic bioavailability was observed in both phases (P<0.05). According to in
vitro experiments, the addition of the same amount of different iron minerals had
contributed to the decrease in arsenic bioavailability to varying extents in
contrast with the blank group, in the descending order of ferrihydrite(F1) >
goethite(G1) > hematite(H1) (F2 > G2 > H2). Total arsenic in exchangeable (F1)
and specifically sorbed (F2) state was found positively correlated with arsenic
bioavailability in gastric phase by PBET, SBRC and IVG methods, the correlation
coefficient of which being r=0.93, P=0.002, r=0.90, P=0.004 and r=0.89,P=0.006,
respectively. It was also found that arsenic bioavailability in gastric phase was
positively correlated with total arsenic in F1 and F2 states by
PBET(r=0.94,P=0.001) and IVG (r=0.87,P=0.009) methods, but no significant
correlation was observed by SBRC method. Additionally, three in vitro experiments
showed that amorphous iron bound arsenic had significant negative correlation
with arsenic bioavailability in gastric phase and small intestinal phase, except
that no correlation was found in small intestinal phase by SBRC method.
PMID- 29965596
TI - [Enhanced Electrokinetic Remediation of Heavy Metals Contaminated Soils by
Stainless Steel Electrodes as well as the Phenomenon and Mechanism of Electrode
Corrosion and Crystallization].
AB - Electrode corrosion and salt crystallization are important challenges that
restrict the engineering application of electrokinetic technology. In the present
study, using stainless steel as an electrode, and deionized water (DW), citric
acid (CA) and polyaspartic acid (PASP) as electrolytes, Pb/Cu-contaminated soil
was remediated by electrokinetic. All of the EK experiments were conducted in a 2
L soil cell reactor with a moisture level of about 35% blended with 1000 mg.g-1
of Pb and 778 mg.g-1 of Cu under a constant voltage gradient (1 V.cm-1, 2 V.cm-1)
for 150 h. The removal efficiency of heavy metals and influencing factors, as
well as the phenomenon and mechanism of electrode corrosion and salt
crystallization were explored. The experimental results showed under the action
of electric field, the Ca in the test soil would move to the cathode, and the
crystal was formed in the alkaline condition. Additionally, the conductivity of
the electrode was reduced. During the EK process, water at the anode was
primarily oxidized, undergoing a reduction reaction at the cathode. Because H+
and OH- were transported through the soil by electromigration and electro-osmotic
flow (EOF), changes in soil pH could occur. The concentrations distribution of Pb
Cu appeared to be related to the distribution of soil pH in the cell, which might
be associated with the desorption and hydroxide precipitation of Pb-Cu. PASP
resulted in obvious inhibitory effect on the corrosion of stainless steel
electrode, CA and PASP could clearly destroy the formation of CaCO3 crystal,
while barely effectively disrupted the formation of Ca (OH)2 crystal. Both CA and
PASP could promote the removal of Pb, but the influence of PASP on the removal of
Cu was not obvious, and the effect of CA was very significant. Combined with
different corrosion inhibitor and reinforcing agent, stainless steel can be
chosen as the engineering application electrode in electrokinetic remediation.
PMID- 29965597
TI - [Influence of the Application of Non-Hazardous Sewage Sludge on the Evolution of
Soil Carbon Pool and Carbon Pool Management Index].
AB - The products of non-hazardous commercial sewage sludge were utilized in the
accordance of the national standard in the experiment with sandy fluvo-aquic soil
under wheat-maize rotation system during 2013 to 2015. The experiment focused on
the effects of the use of non-hazardous sewage sludge on soil carbon pool and
carbon pool management index to provide theoretical and technical basis for the
resource utilization of non-hazardous sewage sludge. The results showed that
compared with CK, soil amended sludge significantly improved soil total organic
carbon (TOC), soil microbial biomass carbon (SMBC), labile organic carbon
(LOC),and dissolved organic carbon (DOC) to 8.40-14.74 g.kg-1, 164.45-257.45
mg.kg-1, 3.58-4.88 g.kg-1and 81.16-101.58 mg.kg-1, soil amended sludge
significantly enhanced SMBC, LOC and DOC by 84.00%-188.07%, 26.26%-58.03%, and
109.58%-185.39% (P<0.05) respectively, and 45 t.hm-2 sewage sludge (W3) had the
most significant impact on soil carbon pool. The soil microbial entropy
(SMBC/TOC), and utilization of labile organic carbon (LOC/TOC) increased by 8.02%
2.77% and 13.75%-46.48% respectively, and the utilization of dissolved organic
carbon (DOC/TOC) significantly decreased by 153.45%-195.40% (P<0.05). SMBC/TOC,
LOC/TOC, and DOC/TOC declined in treatments of soil amended sludge due to
increased application of sewage sludge, which indicated that soil amended with 45
t.hm-2 of the sewage sludge improved the content of stable carbon resulting in
the decease of the ratio. L and LI decreased with the increasing amount of sewage
sludge indicating that soil amended with 45 t.hm-2 of the sewage sludge improved
the content of stable carbon and was conducive to the accumulation of organic
carbon. Soil amended with sludge significantly increased carbon pool management
index (CMPI) by 153.45%-195.40% (P<0.05), and W3 had the most significant effect
on CMPI. Compared with TOC, CMPI could be more sensitive and direct to reflect
the dynamic changes of soil nutrients and carbon pools through the correlation
analysis and redundancy analysis. In summary, the application of 15-45 t.hm-2
sewage sludge could significantly enhance the soil carbon pool and carbon pool
management index, especially 45 t.hm-2 sewage sludge (W3).
PMID- 29965598
TI - [Input and Distribution of Photosynthesized Carbon in Soil-Rice System Affected
by Water Management and Nitrogen Fertilization].
AB - Fertilizer and water management are two key factors for rice growth. A better
understanding of the carbon (C) cycling in paddy soil requires investigation into
the input characteristics and distribution dynamics of photosynthesized carbon in
rice-soil system. We grew rice (Zhongzao 39) in PVC pots and used the 13 C-CO2
continuous labeling method to quantify the allocation of photosynthesized carbon
in rice-soil system under two regimes(Drying-rewetting vs. continuous watering)
and N fertilization (250 mg.kg-1vs. no addition). The results showed that
nitrogen fertilizer application increased rice shoot biomass and the amount of C
and N, but had no significant influence on rice root biomass. Thus, nitrogen
fertilizer application decreased rice biomass root/shoot ratio significantly.
Drying-rewetting with N fertilizer treatment resulted in higher total C and N
amount by 22% and 33%, respectively, in the shoot, and by 36% and 44%,
respectively in the root than continuous watering with nitrogen fertilizer
treatment. These results indicated that nitrogen fertilizer application promoted
the growth of rice shoot. Nitrogen fertilizer application significantly increased
the 13 C content in rice shoot by 32%-83% over the control without N addition.
Nitrogen fertilizer application also increased the 13 C recovery in rice shoot by
6%-32%, but decreased that in the root by 18%-59%. Pertaining to water effect,
drying-rewetting with N application increased the amount of 13 C in rice shoot
and root. However, without N addition, the amount and the recovery of 13 C in
shoot dropped by 10.3 mg.pot-1 and 12%, respectively, compared with the
continuous watering treatment. The root, on the other hand, recorded increases in
both the amount and the recovery of 13 C by 1.9 mg.pot-1 and 57%, respectively.
Furthermore, the deposition of assimilated C into rhizosphere-soil increased by
both the individual and the interactive effects of N fertilizer application and
drying-rewetting treatment. Thus, combining N fertilizer and drying-rewetting
water management led to more increased allocation and deposition of
photosynthesized carbon in soil-rice system compared with combined continuous
flooding and N application. This study was able to quantify the partitioning and
allocation of rice photosynthesized carbon into different plant and soil pools
under different water and N fertilizer treatments, and can serve as a useful
guide for better water and nutrient management practices in paddy-rice production
that can achieve both sustainable high yield and sequestration of more C within
the paddy soil system.
PMID- 29965599
TI - [Effects of Simulated Acid Rain on Soil Respiration and Heterotrophic Respiration
in a Secondary Forest].
AB - In order to investigate the effects of simulated acid rain on soil respiration
and heterotrophic respiration in a secondary forest, a field experiment was
carried out. A split-plot experiment was arranged in field. There were 4 blocks;
each block had two main plots which were trenched and un-trenched plots. In each
main plot, 4 simulated acid rain treatments of control (CK), pH 4.0 (A1), pH 3.0
(A2), and pH 2.0 (A3) were randomly assigned. Soil respiration in the un-trenched
plots and heterotrophic respiration in the trenched plots were measured weekly.
Soil temperature and moisture at a depth of 5 cm were measured during the
respiration measurements. The results indicated that different simulated acid
rain treatments exhibited similar seasonal patterns of soil respiration and
heterotrophic respiration. Heterotrophic respiration in the trenched plots was
significantly lower than soil respiration in the un-trenched plots. The annual
mean soil respiration rates for the CK, A1, A2, and A3 treatments in the un
trenched plots were (2.47+/-0.31), (2.52+/-0.22), (2.38+/-0.17), and (2.43+/
0.22) MUmol.(m2.s)-1, respectively, while the annual mean heterotrophic
respiration rates for the 4 treatments in the trenched plots were (1.55+/-0.10),
(1.65+/-0.22), (1.77+/-0.08), and (1.78+/-0.27) MUmol.(m2.s)-1, respectively.
ANOVA showed that simulated acid rain had no significant effects on soil
respiration in the un-trenched plots and heterotrophic respiration in the
trenched plots. Regression analysis suggested that there was a significant linear
regression relationship between soil respiration and heterotrophic respiration.
Simulated acid rain significantly (P<0.001) decreased the ratio of soil
respiration to heterotrophic respiration. Soil temperature was the main
controlling factor regulating the seasonal patterns of soil respiration and
heterotrophic respiration for each of the SAR treatment, while soil moisture had
no significant effects on the seasonal variability in soil respiration and
heterotrophic respiration.
PMID- 29965600
TI - [Response of Soil Nitrifier and Denitrifier Community and Activity to Elevated
Atmospheric CO2 Concentration and Temperature].
AB - Elevated atmospheric CO2 concentration and temperature may affect nitrifiers and
denitrifiers which are related to soil N turnover. A climate change experiment
was conducted in the rice-wheat rotation ecosystem. This study was used to
investigate effects of elevated CO2 and temperature on soil microbial community
structure, as well as abundance and activity of nitrifiers and denitrifiers. The
results showed that no change in the abundance of ammonia-oxidizing bacteria
(AOB) and denitrifier was observed at the tillering stage, however at the later
stages, elevated CO2 alone significantly increased the abundance of ammonia
oxidizing archaea (AOA) and denitrifier but there were no changes under CW
treatment. The analysis of T-RFLP profiles showed that elevated CO2 and
temperature had no obvious effect on community structure of AOA, AOB or
denitrifier, but altered diversity index (H') of AOA and denitrifier. Moreover,
elevated CO2 alone significantly increased nitrifying rate at the ripening stage.
Elevated CO2 and temperature did not result in significant change in denitrifying
rate at each single stage. These results suggested that effects of elevated CO2
and temperature on microbial community were different among the tillering,
heading and ripening stages, and functional microorganism responded differently
to multiple climate change treatments.
PMID- 29965601
TI - [Effects of Lithology on the Abundance and Composition of Soil Nitrogen-fixing
Bacteria and Arbuscular Mycorrhizal Fungal Communities in Karst Shrub Ecosystem].
AB - Lithology is a key factor when used to restore vegetation in karst degraded
ecosystems, and arbuscular mycorrhizal (AM) fungi and nitrogen-fixing bacteria
play an important role in improving plant growth. However, little information is
available regarding the effects of lithology on these two groups of
microorganisms. To test whether these microbial communities are impacted by
lithology, the abundance and composition of soil AM fungal and nitrogen-fixing
bacteria communities were determined through terminal restriction fragment length
polymorphism (T-RFLP) and real-time fluorescence-based quantitative PCR (real
time PCR). Three types of lithology (dolomite, limestone and dolomite-limestone)
were selected in this study. The diversity, richness, and evenness of plant
species were evaluated through field surveys and soil properties were measured.
The results showed that the abundances of soil nitrogen-fixing bacteria and
arbuscular mycorrhizal fungal communities were significantly influenced by
lithology. The abundances of these two groups of microorganisms were the lowest
in dolomite soil, inferior to dolomite-limestone soil, while highest in limestone
soil. Similarly, the composition of soil nitrogen-fixing bacteria and AM fungi
communities varied among lithology. A significant linear correlation was observed
among soil organic carbon, available phosphorus, clay content and nitrogen-fixing
bacterial abundance (P<0.05), and a significant linear correlation among total
nitrogen, clay content and AM fungal abundance (P<0.05). Redundancy analysis
showed that the composition of nitrogen-fixing bacterial community was closely
linked to plant evenness, and the AM fungal community composition was closely
linked to plant diversity (plant evenness, Shannon-wiener and richness). These
results indicated that lithology influenced the abundances and compositions of
soil nitrogen-fixing bacteria and arbuscular mycorrhizal (AM) fungal communities
mainly through plant and soil properties.
PMID- 29965602
TI - [Characterization of Phosphorus Forms in Organic Composts and Their Effects on
Leaf Phosphorus Content of Castanea mollissima in Chinese Chestnut Producing
Area].
AB - Characterization of the forms of phosphorus (P) in four organic composts
including compost of hulls and leaves of Castanea mollissima, edible fungi
residues, corn stalks and chicken manure (BYZ), compost of edible fungi residues
and chicken manure(ZF), composts of hulls and leaves of C. mollissima, edible
fungi residues and chicken manure (BZ1 and BZ2) in Chinese chestnut producing
area was conducted by sequential P fractionation developed by Dou et al. Field
trial was conducted to study the effects of compost application on leaf
phosphorus content of Castanea mollissima. The results showed that total
phosphorus content(TP) of organic composts ranked as follows:BZ1(10.61 g.kg-1) >
ZF(9.03 g.kg-1) > BYZ(8.56 g.kg-1) > BZ2(7.68 g.kg-1), and the inorganic
phosphorus(Pi) accounted for 62.88%-73.62% of the total phosphorus in the organic
composts. The content and proportion of HCl-P in the total fractionated
phosphorus(Prt) was the highest among P forms in ZF, while that of H2O-P was the
highest in BYZ, BZ1 and BZ2. The content of NaOH-P was very low in all the
composts. Active H2O-Por NaHCO3-P had the highest inorganic phosphorus
proportion(89.17%-96.00%) of all the P forms. The major Piforms in BZ2 were H2O-
and HCl-extractable P fractions, while H2O-Pi, HCl-Pi and NaHCO3-Pi were major Pi
forms in BYZ, BZ1 and ZF. Residual-P was the predominant organic phosphorus form,
and BZ2 showed the highest Residual-P proportion of the total fractionated
phosphorus(Prt) among all the composts. Leaf phosphorus contents per unit area of
Castanea mollissima by field trial on the added phosphorus-equivalent basis were
expressed as:BZ2>BZ1>BYZ>ZF>CK. Increment of leaf phosphorus content per unit
area in Julyand per month on average showed positive relationship with the
content and proportion of H2O-Pi in the total fractionated phosphorus of
composts, which presumably played a key role in leaf phosphorus absorption of C.
mollissima measured in the year of deep concentrated fertilization. The results
suggested that composts of hulls and leaves of C. mollissima, edible fungi
residues and chicken manure (BZ2) was a good choice in given area for aerobic
composting raw material system in which organic wastes from Chinese chestnut
industry accounted for 80% (hulls and leaves of Castanea mollissima and edible
fungi residues accounted for 60% and 20% respectively), which had a high
proportion of H2O-Pi and organic Residual-P pool and led to the highest leaf
phosphorus content of C. mollissima.
PMID- 29965603
TI - [Effects of Acidic Materials on the N Transformations During the Composting of
Pig Manure and Wheat Straw].
AB - Understanding the effects of acidic materials on the N transformations becomes of
critical importance to choose the additives with preserving nitrogen during the
manure composting. A 40 d static composting experiment was conducted in the
laboratory to explore the effects of acidic materials on changes of temperature,
pH, EC (electrical conductivity), GI (germination index), N compounds and TOC
(total organic carbon) during the composting of pig manure and wheat straw.Three
acidic materials were selected as the additives, including phosphate fertilizer
(P), rotten apples (A) and vinegar (V). The results showed that the duration with
temperature higher than 50C in four treatments all exceeded ten days and reached
the health standard of high temperature composting. The addition of phosphate
fertilizer delayed the time of the pile entering into the high temperature stage,
decreased the pH, and increased the EC during the whole composting. On a mass
basis, 53.1%, 36.2%, 46.5% and 41.5% of original amount of N in CK, P, A and V
were lost during the first 16 d, but there was still 20% N loss during 16-24 d in
P and V treatments. The NH3-N loss accounted for 26.0%, 11.8%, 21.5% and 20.2% of
the N loss. The addition of acidic materials effectively reduced the N loss and
the emissions of NH3, and the phosphate fertilizer showed the best effect. In the
end of composting, the GI all exceeded 80%, and met maturity requirements.
PMID- 29965604
TI - [Diurnal Variation of SOA Formation Potential from Ambient Air at an Urban Site
in Beijing].
AB - Secondary organic aerosol (SOA) is an important component of atmospheric fine
particles (PM2.5). The study of the diurnal variation of SOA formation potential
is important for understanding the evolution of SOA and its contribution to fine
particle pollution. The oxidation flow reactor (OFR) was used to study the SOA
formation potential of ambient air in summer at an urban site in Beijing. The
high concentration of OH radicals in the reactor can oxidize the volatile organic
compounds (VOCs) and lead to SOA formation. The hour average SOA formation
potential varied between 3.9-9.4 MUg.m-3 in a day and had a higher value at night
than in the daytime. The lowest value of SOA formation potential was about 3.9
MUg.m-3 observed at 16:00 in the afternoon. This variation of SOA formation
potential is consistent with the typical VOCs, such as toluene, and inversely
related to the concentration of ozone. In addition to the impact of change in the
height of the boundary layer, experimental data showed that the reduction of VOCs
in photo-oxidation in the daytime was an important reason for the decrease of SOA
formation potential in daytime. Compared to similar studies in developed
countries, the SOA formation potential was higher in Beijing due to the higher
concentrations of VOCs and might make an important contribution to the fine
particle pollution in Beijing.
PMID- 29965605
TI - [Characteristics of Key Size Spectrum of PM2.5 Affecting Winter Haze Pollution in
Taiyuan].
AB - PM2.5 is generally considered as a main pollutant causing the formation of haze.
Based on meteorological parameters, aerosol distribution, and PM monitoring data
in Taiyuan during November and December 2016, the characteristics of the key size
spectrum of PM2.5 affecting haze were discussed. During the observation period,
haze was frequent and serious. Heavy haze time accounts for 25.35% of the total
haze time. Haze events occurred frequently when the relative humidity was greater
than 80% and wind speed was less than 1.5 m.s-1, especially for severe haze. Mild
and moderate level haze occurred frequently when the relative humidity was less
than 80% and greater than 40% and when wind speed was less than 1.5 m.s-1. Slight
haze mainly occurred when the relative humidity was 20%-40% and the wind speed
was 1.25-2.55 m.s-1. The average mass concentration of PM2.5 was 209.45 MUg.m-3,
which was three times the level during non-haze events. With an increase in the
haze level, the mass concentration of PM2.5 and the ratio of PM2.5/PM10
increased. PM1 was the key particle size affecting haze in the low humidity
environment. PM0.5 was the key particle size that affects slight haze, mild haze,
and moderate haze in the high humidity environment, while PM1 was the key
particle size that affects heavy haze. The contribution of surface concentration
to visibility decreased with high humidity, but the particle size increased by
moisture absorption leading to an increase in the extinction efficiency factor,
which compensated for the lack of surface concentration. The increase in the
particle size parameter was an important factor for PM2.5 affecting the haze
pollution with high humidity.
PMID- 29965606
TI - [Characteristics and Source Apportionment of Water-soluble Ions in PM2.5 During
Winter in Panjin].
AB - In order to study the characteristics and source of water-soluble ions in PM2.5
in Panjin, PM2.5 samples were collected at three sites in January of 2017, and
the levels of eight ions (Na+, Mg2+, Ca2+, K+, NH4+, SO42-, Cl-, and NO3-) were
determined by ICS-900 ion chromatograph. The characteristics of PM2.5, the water
soluble ion concentration, SOR and NOR calculation, and ion balance calculation
were investigated, and a principal component analysis was conducted. The results
showed that the concentration of PM2.5 and water-soluble ions followed a
descending sequence of park > development zone > the second middle school. SO42-,
NO3-, and NH4+ were the major components of the water-soluble ions at the three
sampling sites. SOR and NOR values were all higher than 0.10, indicating that
SO42- and NO3- were mainly converted from SO2 and NOx. The ion balance
calculation demonstrated that the cationic and anion equivalents in Panjin had
great correlation in winter. Further study showed that the atmosphere in the
development zone presented as neutral and that in the cultural park and the
second middle school presented as partially alkaline. The principal component
analysis further indicated that the water-soluble ions were mainly derived from
fuel combustion, biomass burning, secondary particles, and re-suspended dust in
winter.
PMID- 29965607
TI - [Characteristics and Source Apportionment of Volatile Organic Compounds in the
Rainy Season of Guangzhou City].
AB - Atmospheric volatile organic compounds (VOCs) were measured in an urban area of
Guangzhou on July 2016 using an on-line gas chromatography mass spectrometry/fire
ion detector. Seventy-three VOCs were detected with an average concentration of
(118.83+/-79.40) MUg.m-3, a maximum concentration of 492.42 MUg.m-3, and a
minimum concentration of 10.54 MUg.m-3 during the period. The peak value of the
TVOC concentration appeared at about 07:00 in the morning, indicating that motor
vehicle pollution had a significant contribution at the site. The minimum value
appeared at about 14:00 in the afternoon, related to photochemical losses. High
concentrations were also observed from 21:00 to 24:00, which was probably related
to pollution emissions and boundary layer compression. Source analysis by PMF
showed that the site was mainly affected by five VOC sources: vehicle exhaust,
solvent use, fuel loss at fuel stations, plant emissions, and cooking exhaust,
the contributions of which were 29.79%, 26.61%, 24.86%, 9.91%, and 8.84%,
respectively. Vehicle exhaust was the largest source of VOCs during the daytime,
while the contribution of plant emissions increased significantly at noon. The
contribution of solvent uses and fuel loss at fuel stations rose during the night
and became the main source of VOCs until early morning.
PMID- 29965608
TI - [Emission Characteristics of Dehydrated Sugar and Acephenanthrylene in Particles
from Tropical Forest Burning].
AB - Forest vegetation burning is an important source of atmospheric particulates. In
this study, 22 kinds of typical tropical trees in Southeast Asia, which can be
divided into evergreen trees, deciduous trees, and shrubs, were selected for
experimentation. The emission characteristics of dehydrated sugar,
acephenanthrylene, aceanthrylene, and retene were analyzed. The trend of the
average emission factor for total sugar was evergreen trees (1.56 g.kg-1+/-1.01
g.kg-1) < shrubs (1.99 g.kg-1+/-0.64 g.kg-1) < deciduous trees (5.38 g.kg-1+/
7.18 g.kg-1). Furthermore, the trend of the average emission factor of
acephenanthrylene was evergreen trees (2.63 mg.kg-1+/-2.44 mg.kg-1) ~ shrubs
(2.46 mg.kg-1g+/-2.14 mg.kg-1) < deciduous trees (6.07 mg.kg-1+/-8.50 mg.kg-1).
For ratios of organic biomarkers, the average ratios of Lev/Man for trees and
shrubs were 20.6+/-11.90 and 23.2+/-9.20, respectively. The range of Lev/Man was
5.8-51.5 in this study. The average ratios of AP/AC for trees and shrubs were
7.13+/-5.18 and 5.53+/-1.51, respectively. Compared with the dehydrated sugar,
which was affected by more conditions, the analysis methods of aromatic
hydrocarbons were simple. Furthermore, although the ratio of AP/AC was less
stable than that of FL/PY in this manuscript, AP/AC was less affected by other
sources of pollution and had higher specificity. In conclusion, the advantages
and disadvantages of each organic biomarker can be synthetically considered in
terms of biomass source analysis in order to improve accuracy, and
acephenanthrylene was a better choice than other biomarkers.
PMID- 29965609
TI - [Construction and Application of Vertical Diffusion Index for Analyzing Weather
During Pollution Events in Tianjin].
AB - Based on temperature and wind speed data from the 255 meter tall meteorological
tower, the characteristics of atmospheric stability were analyzed in Tianjin,
with the vertical diffusion index beta and phi constructed by atmospheric
chemical models. This provided information to use the vertical dispersion
analysis method to forecast pollution from weather data. The results show that
the comprehensive use of atmospheric stability and the vertical diffusion index
can provide a better pollution forecast. When the atmospheric stability was D
from 07:00-08:00 and 18:00-20:00, compared to when atmospheric stability was C,
the probability of heavy pollution weather increased by 10 times. If the vertical
diffusion index beta and wind speed index were used to forecast heavy pollution,
the accuracy rate was 67% higher than when using the single wind speed index. The
coefficient between vertical diffusion index phi and PM2.5 mass concentration was
0.8.When the vertical diffusion index phi was less than 0.52, the probability of
heavy pollution was 75%, identifying 59% of heavy pollution events.
PMID- 29965610
TI - [Comparison Between Atmospheric Wet-only and Bulk Nitrogen Depositions at Two
Sites in Subtropical China].
AB - Atmospheric emissions of reactive nitrogen (N) species are at high levels and
have caused high N deposition in China in recent years. In this study,
atmospheric wet-only and bulk N depositions were monitored simultaneously in a
two-year study at an agricultural site (HN) and a forest site (XS) in the Jinjing
River catchment in Changsha County, Hunan Province in subtropical China. The
differences in concentration and deposition of NH4+-N, NO3--N, DON, and TN
between wet-only and bulk N depositions were compared, and the correlation
between wet-only and bulk N depositions was analyzed, with the aim of estimating
atmospheric wet N deposition based on bulk N deposition. During the monitoring
period, NH4+-N was the dominant species in both wet-only and bulk deposition at
the sampling sites. The average values of total N (TN) depositions for wet-only
and bulk depositions at HN were 26.2 and 28.9 kg.(hm2.a)-1, respectively. The
proportions of NH4+-N, NO3--N, and DON in TN in wet-only deposition were 49.7%,
31.3%, and 19.0%, respectively, while the proportions in the bulk deposition were
48.7%, 31.6%, and 19.7%, respectively. The average values of TN depositions for
wet-only and bulk depositions at XS were 23.6 and 27.8 kg.(hm2.a)-1,
respectively. The proportions of NH4+-N, NO3--N, and DON in TN in wet-only
deposition were 53.9%, 34.78%, and 11.4%, respectively, while they were 49.6%,
31.6%, and 18.9%, respectively, for bulk deposition. The concentrations of N
species in wet-only and bulk depositions were significantly and negatively
correlated with precipitation, while the amount of N deposition was significantly
and positively correlated with precipitation. The concentrations of N species in
wet-only deposition had a significant linear correlation with those in the bulk
deposition at the two sites (R2>0.82). According to the regression equation for
wet-only and bulk N deposition at the monitoring sites, the proportions of NH4+
N, NO3--N, and TN in wet-only to bulk deposition were 0.875, 0.774, and 0.852,
respectively, at HN and 0.859, 0.783, and 0.819, respectively, at XS. These
values were mainly related to the amount of wet-only N deposition and the
pollution level of atmospheric particulate N species at the monitoring sites. In
the subtropical region of China, atmospheric wet N deposition can be
overestimated by 10% to 18% when the atmospheric bulk N deposition is used to
replace the wet N deposition. Based on the regression equation between
atmospheric bulk N deposition and wet N deposition, the atmospheric wet N
deposition can be estimated well using the atmospheric bulk N deposition data.
PMID- 29965611
TI - [Emission Reduction Benefits When Eliminating Yellow-label Vehicles in the Jing
jin-ji Region].
AB - In order to evaluate policy implementation for yellow-label vehicles (namely,
those that fail to meet the Chinese No.1 standard for exhaust emissions), and to
compare the policy of an early elimination subsidy with traffic restrictions of
these vehicles, the emission factor method was adopted to calculate the emission
reduction resulting from the two policies in the Jing-jin-ji Region. The results
showed that: 1 The policies led to good emission reductions for the Jing-jin-ji
Region. Since the implementation of the policies, the cumulative reductions of
CO, HC, NOx, PM2.5, and PM10 have been 5003.2 kt, 397.9 kt, 318.2 kt, 9.6 kt, and
10.6 kt, respectively. 2 The pollutants reduced most prominently were CO, HC, and
NOx, which contributed greatly to the emission reductions and air pollution
control. 3 The main motorcycle types for the CO and HC emission reductions were
small gasoline-powered passenger vehicles and light duty gasoline-powered
vehicles. Heavy duty diesel cars contributed the most to the emission reduction
of NOx and particulate matters. 4 The emission reductions for CO, HC, and NOx
were greater in densely populated urban areas in the Jing-jin-ji Region. The
emission reductions of CO and HC in Beijing, Tianjin, and Shijiazhuang were more
obvious than in other cities, and the emission reductions of NOx and particulate
matters were more obvious in Tianjin, Shijiazhuang, Tangshan, and Handan. 5
Comparing the two policies of an early elimination subsidy and traffic
restriction, the emission reduction of the former policy is continuous for a few
years, and the effectiveness of reduction is significant in several years.
However, the effectiveness of the latter policy decreases with time.
PMID- 29965612
TI - [Health Assessment of the Stream Ecosystem in the North Canal River Basin,
Beijing, China].
AB - With increasing urbanization, the stream ecosystem in Beijing has faced great
challenges. Phytoplankton, benthic macroinvertebrates, and water quality were
investigated based on 25 sampling sites in the North Canal River basin in July
2015, and the quality of the habitat was assessed in situ. A total of 22 metrics,
including aquatic organism, hydrology, water quality, and habitat, were
calculated to be the candidate indicators. A principal component analysis (PCA)
and correlation analysis were used to select the core metrics from the candidate
indicators, and the weight of each core metric was estimated by using the entropy
method. The integrated index of stream ecological health was constructed to
assess the health condition of the North Canal River basin. The results of the
PCA and correlation analysis showed that nine metrics were selected as the core
metrics to construct the integrated index of stream ecological health, i. e., the
Shannon-Wiener diversity index of phytoplankton and benthic macroinvertebrates,
water temperature, BOD5, NH4+-N, F-, Zn, petroleum, and the qualitative habitat
evaluation index (QHEI). According to the results of the health assessment, 12%
of the sampling sites in the North Canal River basin were considered to be
healthy (I) or sub-healthy (II), and more than half were poor (IV) or bad (V).
Therefore, the aquatic ecosystem in the North Canal River basin was generally
unhealthy. The upstream was better than the midstream and downstream, where the
spatial heterogeneity of the health condition was strong. The health condition in
the Nansha River, the midstream of the Qinghe River, and the main stream of the
Tonghui River were poor, while the upstream of the Liangshui River and the
tributaries of the Wenyu River were good. In general, the condition of the stream
ecosystem in the North Canal River basin was relatively complicated.
PMID- 29965613
TI - [Pollution Characteristics and Source Identification of Polycyclic Aromatic
Hydrocarbons and Phthalic Acid Esters During High Water Level Periods in the
Wuhan Section of the Yangtze River, China].
AB - Persistent organic pollutants (POPs) have been detected extensively in water and
sediments in China, causing potential risks to the environment and human beings.
In this study, the content level, distribution characteristics, and pollution
sources of PAHs and PAEs in the water and sediments collected from 15 sites in
the Wuhan section of the Yangtze River in August of 2016 were analyzed
systematically. The following conclusions were made. The total PAHs
concentrations were 20.8-90.4 ng.L-1 (mean value 40.7 ng.L-1) in water and 46.1
424.0 ng.g-1 (mean value 191.8 ng.g-1) in the sediments, while for PAEs, they
were 280.9-779.0 ng.L-1 (mean value 538.6 ng.L-1) in water and 1346.2-7641.1 ng.g
1 (mean value 3699.5 ng.g-1) in the sediment. Both PAH and PAE concentrations in
water meet the Chinese national water environmental quality standard (GB 3838
2002) with a low degree of pollution. PAH monomers with two to three rings were
dominant in water, while those with two to three rings and four rings were
dominant in the sediment. DEHP and DBP were the dominant PAE pollutants in both
the water and sediment. The ratio and principal component analysis showed that
the main source of PAHs in water and the sediment were the emission from coal,
biomass combustion, and petroleum sources, while the main sources of PAEs include
the plastic and chemical industries and municipal solid wastes. Two types of POPs
(PAHs and PAEs) in water and sediment have potentially detrimental effects on
human health and monitoring needs to be strengthened. This research provides
basic data and technical support for the protection of the Yangtze River.
PMID- 29965614
TI - [Characteristics of Antibiotic Resistance Genes in Downstream Areas of the
Aojiang River, Fujian Province].
AB - Many cities are located in the downstream areas of rivers. Rapid urbanization may
result in drastic changes in the urban river ecosystem. Antibiotic resistant
genes (ARGs) are considered to be emerging environmental pollutants, which may do
harm to the health of humans and may pose a potential risk for urban ecological
safety by the dissemination and enrichment of ARGs in urban rivers. In this
study, a high-throughput quantitative PCR technique was used to investigate the
diversity and abundance of ARGs at three sites in Lianjiang County and the
estuary of the Aojiang River, Fujian Province. The results show the abundance of
ARGs in the downstream urban area of Lianjiang County (3.9*1010 copies.L-1) is
significantly higher than upstream of the urban area and the estuary of the
Aojiang River. A total of 129 ARGs are detected in the downstream urban area,
which is higher than in the upstream and the estuary. The results also suggest
that ARGs are persistent and not easy to reduce in the natural river following
the occurrence of ARGs and indicated that the urban river is an important
reservoir of ARGs.
PMID- 29965615
TI - [Distribution Characteristics and Risk Assessment of Heavy Metals in the
Sediments of the Estuary of the Tributaries in the Three Gorges Reservoir, SW
China].
AB - To investigate the pollution status of sediments at the junction of the Three
Gorges Reservoir area, sediment samples were collected over four seasons from the
junction of the estuary located at a tributary of the Ruxi River and the Yangtze
River. The content of eight heavy metals (HMs), including Cr, Zn, Mn, Ni, Cu, As,
Cd, and Pb, in sediments was determined by ICP-MS. The results showed the average
levels of investigated HMs (in mg.kg-1) were Cr (45.24), Zn (46.46), Mn (406.14),
Ni (20.885), Cu (12.49), As (7.02), Cd (0.253), and Pb (11.042). The distribution
analysis indicated that the levels of HMs at the river mouth were higher than
that of the tributaries of the middle reaches and the two sections nearby. The
seasonal distribution shows that the heavy metal content in the spring sediment
is higher than in summer, autumn and winter. In addition, the correlation
analysis indicated that the eight HMs possessed similar homologous
characteristics and had common exogenous inputs. The assessment of the Geo
Accumulation Index showed slight Cd pollution in the estuary of Ruxi River, and
the Potential Ecological Risk index showed that Cd presented moderate ecological
risks. The toxic effect of benthonic organisms was possibly correlated to Ni
contamination at the intersection of the tributary and main stream, which was
supported by the evidence from the sediment quality criteria. In conclusion, the
rating of ecological risk at the mouth of the Ruxi River tributary is slight.
PMID- 29965616
TI - [Assessment of Physico-chemical Properties and Phosphorus Fraction Distribution
Characteristics in Sediments after Impounding of the Three Gorges Reservoir to
175 m].
AB - In order to understand the characteristics of the distribution of sediment total
phosphorus (TP) and phosphorus fractions in the mainstream sediments in the Three
Gorges Reservoir (TGR) after impounding the water level to 175 m, 13 surface
sediment samples were collected from the Wujiang to Maoping sections in October
2010. The physico-chemical properties, including organic matter content, particle
grain size distribution, and major mineral analysis, as well as total phosphorus
and its fractions in the sediment, were determined. Moreover, the relationships
among phosphorus fractions, organic matter contents, and particle grain size were
discussed, and the effect of the impoundment on sediment phosphorus accumulation
and bioavailability was also evaluated. Results indicated that the sediment
organic matter content of the TGR was between 7.79 g.kg-1 and 55.63 g.kg-1, and
the main mineral components were chlorite, illite, and quartz. The sediments were
dominated with clayey silt with a median diameter (d50) ranging from 3.84 MUm to
23.65 MUm. The measured total phosphorus content of the sediments were between
557.06 g.kg-1 and 837.92 g.kg-1, and the total phosphorus enrichment index of
each sampling site is greater than 1, demonstrating a potential risk for
phosphorus pollution. The calcium bound phosphorus (Ca-P) and the reductant
soluble phosphorus (Oc-P) were the dominant sediment phosphorus fractions, while
the exchangeable phosphorus (Ex-P), the iron bound phosphorus (Fe-P), and
aluminum bound phosphorus (Al-P) content were relatively low. Bioavailable P only
accounts for 2%-8% of the total phosphorus content. When referring to previous
studies, the sediment particle size tended to be smaller and the content of
comparatively easy-to-weather minerals slightly increased with the increase of
the impoundment water level. However, the increase in the impoundment water level
did not result in a significant increase tendency in sediment TP content. In the
future, a reduction in sediment input and a decline in sediment particle size may
facilitate the accumulation of phosphorus in the sediments in the broad valley
section of the TGR. Moreover, large scale dry-wet alternation in the water level
fluctuation zone and resuspension of floating mud near the dam both potentially
impact the bioavailability of phosphorus in the sediments.
PMID- 29965617
TI - [Source of Nitrate in Surface Water and Shallow Groundwater Around Baiyangdian
Lake Area Based on Hydrochemical and Stable Isotopes].
AB - In order to study the source of nitrate in surface water and groundwater near a
domestic sewage discharge river in the Baiyangdian watershed, including the Fuhe
River and Baiyangdian Lake, shallow groundwater and deep groundwater samples were
collected in July 2014.Water chemistry and stable isotopes (delta2 H and
delta18O) were used to study the relationship between the surface water and
groundwater. delta15 N was used to explore the source of nitrate. The results
show that urban and rural domestic sewage discharge to Fuhe River and then
experience evaporation. Shallow groundwater is affected by the Fuhe River,
Baiyangdian Lake, and lateral recharge from groundwater in the Taihang Mountain
area. There are 16.7% of shallow groundwater samples exceeds the NO3- threshold
for drinking water according to the World Health Organization standard. Due to
the effect of self-purification capacity, the NO3- mass concentration in the Fuhe
River is higher in the upstream area than in the downstream area. Due the
regional water flow from northwest to southeast, the NO3- mass concentration in
the shallow groundwater is higher in the south bank area than in north bank area.
The shallow groundwater near the Fuhe River and Baiyangdian Lake is recharged by
surface water. In addition, soil, fertilizer, and point sources are also major
sources for groundwater nitrate. Urban and rural residential living and
agricultural production activities are the main reasons for surface water and
groundwater nitrate.
PMID- 29965618
TI - [Thermal Stratification and Its Impacts on Water Quality in Shahe Reservoir,
Liyang, China].
AB - Based on the one-year hourly water temperature profiles and the associated
environmental drivers during the past eight years in Shahe Reservoir, Jiangsu
Province, China from 2009 to 2016, the factors underlying the seasonal variation
of thermal stratification and water quality response were investigated. It was
shown that the thermal stratification was a typical subtropical one-cycle mixing
model, lasting from May to September. The thermal stratification appeared and
disappeared when the surface water temperature was 21 C in the late spring and 19
C in the middle of autumn. The difference between the water temperature at the
epilimnion and hypolimnion increased with increasing solar radiation. When the
air temperature was above 30 C, the stability of the thermal stratification
increased. Heavy storms reduced the temperature of the surface water and weakened
the temperature stratification of the column above a 5 m depth but had limited
impact on the stratification of the hypolimnion deeper than 5 m. The thermal
stratification greatly impacted the water quality of the lake. Hypoxia in the
bottom water occurred by thermal stratification, leading to increased NH4+-N. The
concentrations of dissolved oxygen, total phosphorus, and suspended solids in the
hypolimnion increased after the disappearance of thermal stratification. Our
results indicated that the thermal stratification was mainly controlled by solar
radiation and the thermal stratification favored the growth of cyanobacteria and
led to the release of nutrients from the sediment, threatening the water quality.
Attention should be paid to thermal stratification to prevent algal blooms and
related water quality deterioration.
PMID- 29965619
TI - [Spatial and Temporal Variation Characteristics of Drip Water Hydrogeochemistry
in the Xueyu Cave of Chongqing and Its Implications for Environmental Research].
AB - Geochemical indexes of drip water were monitored to unveil their seasonal
variability and response mechanism to the external climate from March 2015 to
March 2017 at four sites in Xueyu Cave, Chongqing municipality. The results
showed that four drips show a significant difference in ion concentration and
discharge despite all sites having simple HCO3--Ca2+ waters and being super
saturated with respect to calcite. Being subject to geochemical processes, such
as bedrock dissolution, dilution, and prior calcite precipitation (PCP), the
geochemistry indexes, such as Ca2+, Mg2+, HCO3-, EC, pH, pCO2, and SIc, at the
four sites showed extraordinary seasonal variations and could perfectly respond
to external climate events. Due to the difference of migration pathways and PCP
intension, different types of drip water had diverse seasonal variations in
Mg/Ca. Affected by soil CO2 content and hydrodynamic conditions, the delta13CDIC
of all sites had correlations with external temperature or precipitation. On a
short time scale, the delta13CDIC values reflected the precipitation amount in
the site with its flow path controlled by conduit flow.
PMID- 29965620
TI - [Distinguishing the Compositions and Sources of the Chromophoric Dissolved
Organic Matter in a Typical Karst River During the Dry Season: A Case Study in
Bitan River, Jinfo Mountain].
AB - Since resistant dissolved organic matter (RDOM) plays a critically important role
in a karst carbon sink, one of the most important continental carbon sinks,
research focusing on the origination, transportation, and translation of RDOM in
a karst water system is important. Currently, 3D-fluorescence EEMs are used to
detect the composition and origination of chromophoric dissolved organic matter
(CDOM), an important part of RDOM. This is a very fast and efficient method for
CDOM analysis. In this study, 3D-fluorencence EEMs combined with UV-visible
absorption spectrum were used to analyze the composition and origination of CDOM
in the Bitan River at Jinfo Mountain. Samples were collected from nine sampling
sites from January to March 2017 and analyzed with CDOM EEMs and UV-visible
absorption spectrums. In addition hydrochemical characteristics were determined
and then samples were stimulated with PARAFAC to detect the chromophoric
fluorescent groups and indexes. The PARAFAC stimulation revealed three
chromophoric fluorescent groups in which fulvic acid was the largest component,
accounting for about 44%, with a humic acid content of about 32% and tyrosine
like acid content of about 24%. Four indexes: FI, BIX, HIX, and beta?alpha, were
calculated, and the mean values were 2.06, 0.87, 4.35 and 0.69, which showed
relatively high FI, BIX, and beta?alpha values and a low HIX value, implying that
the CDOM was autochthonous and originated from microbes and aquatic plants in the
dry season. The spatial dynamic of the index revealed an increased BIX and
decreased HIX from the upstream area to the downstream area, implying the impact
of land-use and human activities. The forest soil input more humic acid and
agriculture input more N and P resulting in flourishing aquatic plants and
microbes. Moreover, the correlation coefficients of DIC and humic acid, tyrosine
like acid were 0.515 (P<0.05) and 0.644 (P<0.01), from which it could be inferred
that DIC contributed to CDOM formation. The conclusions of this study revealed
that DIC would be fixed by karst water aquatic plants and microbes and then sink
as autochthonous CDOM and become part of karst water carbon sink.
PMID- 29965621
TI - [Environmental Significance of the Stable Isotopes in Precipitation at Different
Altitudes in the Tuolai River Basin].
AB - Precipitation samples and meteorological data were collected simultaneously
during individual precipitation events at Tuole station (3367 m a.s.l.) and
Jiayuguan station (1658 m a.s.l.) in the Tuolai River Basin. A study of temporal
variation, Local Meteoric Water Lines, and altitude change on precipitation
stable isotopes was conducted. The relationships between precipitation stable
isotopes and temperature, precipitation, average vapor pressure, and relative
humidity were determined in order to explore the environmental significance of
the stable isotopes at different altitudes in the middle reaches of the Qilian
Mountains. The analysis indicated that the stable isotopes of the precipitation
in Tuole and Jiayuguan station were characterized by pronounced seasonal
variation, with Tuole having higher delta18O values in summer and autumn and
lower delta18O values in spring and winter, while Jiayuguan displays higher
delta18O values in spring and lower in other seasons. The d-excess was correlated
negatively with delta18O, and the correlation coefficients between delta18O and d
excess decreased with increasing altitude due to weakening sub-cloud evaporation.
The slope and intercept of the Local Meteoric Water Lines from Jiayuguan to Tuole
rose significantly, showing an increasing trend from low altitude to high
altitude. For the precipitation events above 10C, delta18O of Tuole was
positively correlated with the temperature, but the Jiayuguan results indicated
the opposite. Sub-cloud evaporation weakened with high precipitation events in
Jiayuguan. delta18O and d-excess were positively correlated with the average
vapor pressure, which declined from Tuole to Jiayuguan. Since the water vapor
pressure and saturated water vapor pressure increased, it was difficult to form
precipitation with decreasing altitude. The local strong sub-cloud evaporation
caused delta18O and deltaD was positive at low altitude, while the effect of
moisture recycling is obvious, such that delta18O and deltaD are negative in high
altitude areas. There is no significant positive correlation between the delta18O
and the relative humidity of the precipitation in Jiayuguan, while Tuole displays
an opposite pattern. The results of the study will provide a scientific basis for
further study of precipitation isotopes in the Tuolai River basin.
PMID- 29965622
TI - [Spatial-Temporal Variations of CO2 and CH4 Flux Through a Water-air Interface
Under the Effect of Primary Productivity in Wulixia Reservoir].
AB - In recent years, the effect of greenhouse gas has been a focus. In order to
reveal the spatial-temporal variations of CO2 and CH4 flux through a water-air
interface, Wulixia reservoir was selected as a typical case for measuring CO2and
CH4 flux using a floating chamber during four study periods in 2016.The primary
productivity of the water was also studied. The results indicate that surface
layer water in Wulixia reservoir is a CO2 sink in summer, varying between -30.14
and -3.47 mg.(m2.h)-1. However, it is the source of CO2 in autumn and winter,
varying between 15.57 mg.(m2.h)-1 and 115.06 mg.(m2.h)-1. The variation of
methane flux is obvious in summer, but it is stable in autumn and winter. The
spatial distribution of CO2 and CH4 show that they are higher in the typical bay
area and lower in the tailing dam as well as in the drawdown zone of the
reservoir. In addition, the spatial and temporal variation of CO2 and CH4 are
negatively and positively correlated with primary productivity (r -0.477 and
0.771), respectively. Due to the high activity of photosynthetic micro- organisms
in summer, CO2 can be sequestered, allowing the surface-layer water in Wulixia
reservoir to be a CO2 sink. In addition, methanogenic bacteria can oxidize
organic carbon produced by photosynthetic micro-organisms. Therefore, CH4 has a
negative correlation with primary productivity. The results provide important
information for the study of microorganism functions in karst water systems.
PMID- 29965623
TI - [Spatiotemporal Succession Characteristics of Algal Functional Groups and Its
Impact Factors for a Typical Channel-Type Reservoir in a Southwest Mountainous
Area].
AB - In order to explore the spatial and temporal variations of algal functional
groups in the Zipingpu reservoir, a typical channel-type reservoir in the
southwest mountainous area of China, water samples were collected from eight
sections of the Zipingpu reservoir from April 2016 to March 2017.A total of 21
algal functional groups were identified as B, C, D, F, G, H1, J, L0, LM, MP, N,
P, S2, T, W1, W2, X1, X2, X3, Y, and Z. Based on the analysis of the dominant
degree (y > 0.02), the algal functional groups were dominated by W2, Y, L0, W1,
MP, and B. The C-R-S strategy of algal growth in the Zipingpu reservoir showed
that R-type was a more dominant type than the S- and C-type for the majority of
the time. Peridinium (group L0, type S) was the significant algae in the Zipingpu
reservoir algal bloom event in June 2016.Redundancy analysis (RDA) was used to
explore the relationship between algal functional groups and environmental
factors. The results showed that algal density, chlorophyll a, water temperature,
and biochemical oxygen demand were the major factors influencing the
spatiotemporal succession of algal functional groups across the eight sampling
sections, with water temperature having the highest influence.
PMID- 29965624
TI - [Seasonal Succession of Phytoplankton Functional Groups and Their Driving Factors
in the Siminghu Reservoir].
AB - The succession of phytoplankton communities is affected by pure environmental
factors as well as the interaction of various factors. Phytoplankton communities
with eleven aquatic abiotic factors and four biotic factors were investigated in
the Siminghu Reservoir, and the seasonal succession of phytoplankton FGs related
to the biotic and abiotic factors was analyzed. The results suggested that a
total of 22 phytoplankton functional groups were identified across the samples,
and they were all affiliated with Chlorophyta and Bacillariophyta. An obvious
seasonal succession was discovered by NMDS, which were present as D+Lo in summer,
D+P+Lo in autumn and winter, and X2+P+MP in spring. In particular, we screened 10
functional groups with biomass significantly associated with the seasonal change
in the phytoplankton community. A variance partitioning analysis (VPA) revealed
that water temperature-zooplankton covariation and water temperature explained
the variation in the phytoplankton functional groups throughout the year. A
canonical correspondence analysis (CCA) showed that water temperature,
transparency, nitrate nitrogen, and the biomass of zooplankton were the most
critical factors determining the community dynamics of phytoplankton.
PMID- 29965625
TI - [Effects of Nutrient Addition on the Growth and Competition of Bloom Forming
Cyanobacterium Chrysosporum ovalisporum: An In-situ Experiment].
AB - An in-situ mesocosm experiment was conducted to study the growth dynamic of
Chrysosporum ovalisporum and the other phytoplankton organisms under accelerated
eutrophication conditions by using 39 buckets (100 L) in Lake Dishui, Shanghai.
The results showed that the growth of both filamentous cyanobacteria (C.
ovalisporum) and green algae were promoted with nutrient enrichment. The increase
in the algal biomass rate in N plus P addition treatments was significantly
higher than in treatments with N or P alone (P<0.05). Although the increasing
biomass rate with P addition alone was higher than with N alone, there was no
statistically significant difference (P>0.05). The relevant abundance of C.
ovalisporum showed a significantly decreasing trend with N addition treatments
and N plus P additions treatments (P<0.05), although it was slightly increased
with the treatments with P alone (P>0.05). Nutrient addition could significantly
improve the growth of small sized algae organisms (Chroococcus spp., Coelastrum
spp., Chlorella spp., Tetraedron spp., and Scenedesmus spp.) rather than C.
ovalisporum in all treatments (P<0.05). The small sized green algae overcoming C.
ovalisporum indicated that small sized algae were more favored by hyper
eutrophicated, high water temperature and relatively undisturbed conditions. This
is because small sized algal organisms have higher metabolic and growth rates
compared to other sized algae, especially in stationary water regimens and high,
light density conditions. We foresee that the small sized algae, Chlorophyte,
dominating the small hyper-eutrophic aquatic system may be a potential succession
pattern in the high water temperature seasons.
PMID- 29965626
TI - [Purification Effect of Submerged Macrophyte System with Different Plants
Combinations and C/N Ratios].
AB - A submerged macrophyte pond can effectively remove nitrogen and phosphorus from
water, with the removal efficiencies for pollutants depending on combinations of
submerged macrophytes. Moreover, the material structure of sewage also has a
significant impact on the purification effect of the submerged macrophyte system.
This experiment selected three submerged plants (Vallisneris spiralis, Hydrilla
verticillata, and Myriophyllum spicatum) to examine the purification effect of
their combinations on sewage, including nitrogen and phosphorus removal
efficiencies. In addition, the effect of influent C/N ratio on the submerged
macrophyte pond was also tested and discussed. The results showed the following.
1 All plant combinations can decrease concentrations of nitrogen and phosphorus
in water, resulting from nutrient deposition along with sedimentation of
suspended particles. The combinations of Vallisneris spiralis and Hydrilla
verticillata showed the highest purification efficiency for total nitrogen and
total phosphorus with an average removal rate of 32.71% and 22.13%, respectively.
2 The purification effects of three C/N ratio (1.89, 5.93, and 12.09) for
Vallisneris spiralis and Hydrilla verticillate system were different. The removal
efficiency was highest when the C/N ratio was 5.93, with removal rates for total
nitrogen and total phosphorus and a reduction in permanganate index of 81.34%,
68.26%, and 88.65%, respectively. The C/N ratio affected the degradation of
nitrogen, phosphorus, and organic matter by influencing the dissolved oxygen
concentration of water and changing the anaerobic and aerobic environment of the
water. In conclusion, different submerged macrophyte combinations showed better
purification effect than a single type of plant in the submerged plant pond
system. Changing the influent C/N ratio by placing carbon source materials into
the water can greatly increase the removal efficiency of submerged plant pond,
providing a practical reference for the use of submerged plant ponds to treat
sewage.
PMID- 29965627
TI - [Characteristics of Nitrogen and Phosphorus Concentration Dynamics in Natural
Ditches Under an Irrigation-Drainage Unit in the Jianghan Plain].
AB - The paddy field in Jianghan Plain usually exists in the form of an irrigation
drainage unit, and the natural ditch is the main part of the unit. A continuous
in situ monitoring of the natural ditch water level and water quality through the
entire rice growing season in 2015 was conducted to investigate the dynamics of
ditch water level and nitrogen and phosphorus concentration in the ditch. Another
objective was to determine the effect of these factors. Results showed that
during the entire rice growing season, the ditch water depth was maintained
between 30 to 70 cm, and the water depth was higher during irrigation events than
during rainfall events. Fertilization was the main factor affecting the nitrogen
concentration in the ditch water. Two peaks of total nitrogen (TN) concentration
appeared on June 18 and July 30 because of topdressing. In the early stage of
rice growing, ammonia nitrogen (NH4+-N) concentration was higher than that of
nitrate nitrogen (NO3--N). External disturbances (such as rainfall and irrigation
events) were the main factors affecting the total phosphorus (TP) concentration
in the ditch water. The dynamic of TP concentration in the ditch water was large,
and it was consistent with that of the particulate phosphorus (PP) concentration.
Drainage of the irrigation-drainage was mainly controlled artificially. The
period from rice transplanting to 3 days after the first top dressing was
critical in preventing the outflow of ditch water. During the rice harvest stage,
the TN and TP concentration were 0.22 and 0.06 mg.L-1, and the water quality
reached theIIclass standard for surface water quality. This reduced the risk from
drainage from the irrigation-drainage unit to the surrounding water environment.
PMID- 29965628
TI - [Distribution and Treatment of Antibiotics in Typical WWTPs in Small Towns in
China].
AB - As a new, persistent pollutant in the environment, antibiotics are one of the
most important pollutants in sewage treatment plants. The objective of this work
was to investigate the concentration distribution and removal efficiency of
antibiotics for three typical wastewater treatment technologies applied in small
towns (CASS, A2/O, and Orbal oxidation ditch) using solid phase extraction-liquid
chromatography-tandem mass spectrometry. Sixteen typical antibiotics, including
four tetracyclines, three beta-lactams, four macrolides, three quinolones, and
two sulfonamides, were analyzed in the influent and effluent. In addition, the
relationship between the presence of antibiotics and the basic water quality
(NH4+-N, TN, COD, pH, etc.) in the WWTPs was analyzed. The results showed that
ofloxacin (OFX) and norfloxacin (NOR) were the main antibiotics in the WWTPs in
this study. However, the concentrations of these two antibiotics in the effluent
were low, indicating effective antibiotic removal efficiency. The antibiotic
removal efficiency was higher than 60% in five of the WWTPs. Compared with the
A2/O process, the CASS and Orbal oxidation ditch technologies resulted in higher
removals of most of the antibiotics. In addition, the CASS and A2/O processes
worked best for the removal of beta-lactam [ampicillin (AMP) and penicillin
(PCN)], quinolones (ENR, NOR, and OFX), and macrolide (CLR), while the Orbal
oxidation ditch worked best for the removal of tetracyclines (TC and OTC) and
sulfonamides [sulfadiazine (SD)]. The correlation between antibiotic
concentration and the basic parameters of water quality (NH4+-N, TN, COD, pH,
etc.) was analyzed, and it was found that the water quality parameters had some
effect on the concentration of antibiotics. With higher concentrations of the
basic water quality parameters, higher the concentration of erythromycin (EM),
roxithromycin (ROX), 4-epi-Tetracycline (E-TC), clarithromycin (CLR),
ciprofloxacin (CIP), ofloxacin (OFX), epioxytetracycline (E-OTC), tetracyclines
(TC), oxytetracycline (OTC), and norfloxacin (NOR) were observed. In summary, it
is important to ensure the stable operation of small town WWTPs to reduce the
ecological risk of antibiotics.
PMID- 29965629
TI - [Effects and Mechanism of the Combination of Ozone-PAC as a Pretreatment for the
Reduction of Membrane Fouling].
AB - The effects of ozone, powdered activated carbon (PAC), and their combination on
controlling fouling and the removal of organic matter were investigated. The
results showed that ozone mainly oxidized strong hydrophobic, high relative
molecular mass (Mr) compounds and the high Mr was transferred to medium and small
Mr hydrophilic fractions. Ozone could control fouling effectively, demonstrating
that hydrophobic organic matter with higher Mr contributed to membrane fouling.
PAC adsorbed organics with small Mr and alleviated membrane fouling, showing that
organics with small Mr contributed also to membrane fouling. The ozone and PAC
combination controlled membrane fouling and also enhanced the removal of
organics, demonstrating the synergistic effect of such a combination.
PMID- 29965630
TI - [Start-up and Process Characteristics of Simultaneous ANAMMOX and Denitrification
(SAD) in a Pilot-scale Anaerobic Sequencing Batch Reactor (ASBR)].
AB - A pilot scale anaerobic sequencing batch reactor (ASBR, working volume 530 L),
inoculated by anaerobic sludge from an A2O process, was developed to investigate
the start-up of anaerobic ammonia oxidation (ANAMMOX) and its combination with
denitrification for deep-level nitrogen removal from saline wastewater.
Simultaneously, the flora structure was analyzed. Results showed that under the
conditions of temperature 35C+/-1C and reaction time 14 h, ANAMMOX was
successfully started-up after 160 days of operation. During the stabilized
operation stage, ANAMMOX coupled with denitrification (SAD) led to a total
nitrogen (TN) removal efficiency and removal rate of 91.1% and 0.45 kg.(m3.d)-1,
respectively. The successful cultivated sludge formed granules and presented as a
light red color, with the main bacteria genus being Candidatus Brocadia (10.6%).
Additionally, high efficiency nitrogen and organic carbon removal (COD and TN
removal efficiency of 93.2% and 90.0%, respectively) from wastewater simulating
desulfurization and denitrification tailings with high salinity (Cl-
concentration of 8000 mg.L-1) was achieved in the SAD system by gradually
increasing the salinity gradient. Moreover, the denitrification in SAD was mostly
NO3--N->N2, with partial denitrification (NO3--N->NO2--N) accounting for only
30.3%.
PMID- 29965631
TI - [Phosphate Removal on Zirconium Alginate/Poly(N-isopropyl acrylamide) Hydrogel
Beads with a Semi-interpenetrating Network].
AB - Zirconium alginate/poly(N-isopropyl acrylamide) hydrogel beads with a semi
interpenetrating network (ZA/PNIPAM) were prepared by using the ionic
crosslinking and radical polymerization method and investigated for phosphate
removal from aqueous solutions. The effects on the adsorption performance of
hydrogel beads, including initial pH, adsorbent dose, initial phosphate
concentration, and co-existing anions, were evaluated systematically. Results
showed that the ZA/PNIPAM could exhibit a maximum uptake capacity of phosphate at
pH 2.The uptake capacity of the adsorbent increased with a decrease in the dose
or an increase in the initial phosphate concentration. The presence of SO42- had
a more negative effect on phosphate removal compared to Cl- and NO3-. The
kinetics fitted a pseudo-second-order model and intraparticle diffusion model,
suggesting the adsorption rate was mainly controlled by surface adsorption and
diffusion into the interior of the hydrogel beads. The isotherm data could be
described by the Freundlich model, indicating that the adsorption process was
heterogeneous multilayer adsorption. The studies of FTIR, XPS, and zero point of
charge with relevant adsorption data revealed that the phosphate adsorption
mechanisms could be electrostatic attraction (physical adsorption) and ligand
exchange reactions (chemical adsorption). After four cycles of regeneration,
ZA/PNIPAM exhibited a stable uptake capacity, indicating favorable reusability.
PMID- 29965632
TI - [Shortcut Nitrification Rapid Start and Stability of Corn Starch Wastewater].
AB - A rapid startup shortcut nitrification method is researched with suppression
factors, such as high temperature, high pH, low DO, etc., in a SBR reactor, with
anaerobic effluent (C/N 0.93-1.53) from a certain corn starch company wastewater
treatment station. Targeting the already started up shortcut nitrification
system, the stability and control strategy are studied further after cancelling
the high pH and high temperature limiting factors. Results show that shortcut
nitrification (NO2--N accumulation rate above 80%) can be quick-started after 17
cycles of domestication and culture when the controlling temperature is (30+/
1)C, the pH is 7.8-8.2, and the DO of the regular nitrification section is 0.7
1.0 mg.L-1, combined with on-line control of the pH and DO parameters in the
nitrification process. When the limits of high pH and high temperature are
cancelled for the already started-up shortcut nitrification system, long-term
stable operation can be obtained for a shortcut nitrification of NO2--N
accumulation rate above 98% under the conditions of sufficient alkalinity,
temperature 23-24C, and DO 0.7-1.0 mg.L-1 in the regular nitrification section,
combined with the on-line control of nitrification process. The control
strategies can be summarized as: first, the shortcut nitrification is rapidly
started up under high temperature, high pH, and relatively low DO suppression
factors, and then the high pH and high temperature limitation factors are
eliminated. The control strategies have good practical significance for realizing
the long-term stable shortcut nitrification for corn starch wastewater with
relatively high ammonia nitrogen concentration and relatively high temperature.
PMID- 29965633
TI - [Nitrifying Bacteria Culture in Entrapment Immobilization].
AB - In order to realize the industrialization of nitrifying bacteria enrichment
cultivation and large-scale application of entrapment immobilization, activated
sludge from a sewage treatment plant was used as the seed sludge. The
concentration of substrate was increased progressively in an industrialized tank.
Nitrifying bacteria were grown rapidly by controlling the concentration of FA and
FNA, and the ammonia oxidation rate reached 118 mg.(L.h)-1 eventually. The
results of high-throughput sequencing showed that Nitrosomonas, nitrifying
bacteria, was only 0.53% of the bacteria. After exposing it to an enrichment
culture, the content of Nitrosomonas rose to 10.27%, 20 times larger than that in
the raw sludge. Diversity was significantly smaller at the same time. After
embedding immobilization with PVA (polyvinyl alcohol), the embedded fillers
nitrification load was 30%. A continuous-flow approach was utilized in the
recovery phase, and the nitrification loading rate reached a high level, 62
mg.(L.h)-1, and efficient recovery of the biologically active fillers was
achieved.
PMID- 29965634
TI - [Performance of the Removal of Nitrogen During Anaerobic Ammonia Oxidation Using
Different Operational Strategies].
AB - The effects of low substrate ratio, cooling methods, and pH on nitrogen removal
performance were studied in a laboratory-scale anaerobic ammonium oxidation
reactor (ASBR) while treating simulated domestic waste water. The results
illustrated that the average removal efficiencies of NH4+-N and NO2--N increased
from 54.4% and 65.3% to 95.8% and 92.5%, respectively, at a temperature of 30C
and an influent concentration of NO2--N of (30+/-0.2)mg.L-1. The substrate ratio
(NO2--N/NH4+-N) increased from 0.9 to 1.4.However, the removal efficiency of NH4+
N was affected negligibly, and the average removal efficiency of NO2--N decreased
to 54.6% when the substrate ratio was increased to 1.6, suggesting that the
nitrogen removal performance of anaerobic ammonium oxidation was best when the
substrate ratio was close to the theoretical value of 1.32.The average removal
efficiencies of NH4+-N and NO2--N decreased from 97.5% and 98.5% to 35.2% and
40.1%, respectively, when the temperature of the reactor dropped from 30C to 15C
at one time. The average removal efficiencies of NH4+-N and NO2--N dropped from
97.7% and 98.6% to 52.7% and 62.4%, respectively, when the ladder cooling
method(30C->25C->20C->15C) was used. The average removal efficiencies of NH4+-N
and NO2--N increased initially and then decreased when the pH was increased
gradually from 7.7 to 8.5.The highest nitrogen removal efficiency was achieved
when the pH was controlled at 8.3 with a substrate ratio of NO2--N/NH4+-N equal
to 1.4.
PMID- 29965636
TI - [Changes in Heavy Metal Speciation and Release Behavior Before and After Sludge
Composting Under a Phosphate-rich Atmosphere].
AB - Sewage sludge is rich in organic matter, N, and P and could be used as a soil
amendment to improve the status of soil organic matter, soil structural
characteristics, and soil water retention capacity after aerobic composting.
However, heavy metals in sewage sludge have become the main bottleneck limiting
its land application. In addition, with the large-scale exploitation of phosphate
rock resources in our region of interest, a large amount of phosphate tailings
needs to be disposed and a large area of abandoned mining lands needs to be
reclaimed. Phosphate tailings could be auxiliary materials for sewage sludge
composting to immobilize heavy metals, and the compost could be applied for
revegetation of the abandoned mining lands. The contents of As, Cr, Cu, Ni, Pb,
Cd, and Zn were measured, and a successive extraction procedure was used to
investigate the change in speciation of heavy metals in the sludge before and
after the phosphate-rich composting. pH-dependent leaching tests were carried out
to further evaluate the immobilization effects of composting on heavy metals and
the release potential under different pH conditions. The results showed that the
contents of heavy metals in the compost satisfied the corresponding threshold for
land reclamation. Adding phosphate tailings greatly improved the stability of
heavy metals during the composting process. The portion of stable residues of Pb,
Cd, As, and Zn in the phosphate-rich compost was 84.00%, 58.00%, 68.50%, and
30.93%, respectively, compared with 68.10%, 30.50%, 40.32%, and 16.48% for the
control, compost without adding the phosphate tailings. Meanwhile, the maximum
leaching potential of As, Ni, Pb, Zn, and Cu in the phosphate-rich compost
decreased from 3.692 mg.kg-1, 0.903 mg.kg-1, 0.217 mg.kg-1, 7.225 mg.kg-1, and
8.725 mg.kg-1 to 0.684 mg.kg-1, 0.586 mg.kg-1, 0.071 mg.kg-1, 2.603 mg.kg-1, and
6.935 mg.kg-1in the control, respectively, for pH 6-8.It could be concluded that
the addition of phosphate tailings in the sludge composting lowered the risk of
heavy metals in sewage sludge compost to make it favorable for beneficial use in
abandoned mining land reclamation.
PMID- 29965635
TI - [Transformation of Protein in Sludge During High Solids Anaerobic Digestion].
AB - Dewatered waste sludge with a total solid (TS) concentration of 12% was used for
mesophilic (37C) anaerobic digestion (AD). The biotransformation mechanism of
protein and the reason for the low conversion efficiency of protein under high
solids AD was investigated by analyzing the variation of protein composition in
the sludge before and after AD. The results showed that the conversion rate of
protein in the sludge was 34.26% after 45 days of AD. The reason for the low
efficiency of protein conversion was the poor mass transfer efficiency under the
condition of high solids content and the large amount of ammonia nitrogen
produced with the hydrolysis. After 45 days of AD, the total ammonia nitrogen
(TAN) concentration reached 1201 mg.L-1, which resulted in the inhibition of the
AD process, especially the decomposition of protein. Some of the protein
converted to humic acid-like and fulvic acid-like substances, which are more
difficult to decompose based on the three-dimensional fluorescence spectroscopy
(3D-EEM) analysis. Two-dimensional electrophoresis (2-DE)- mass spectrometry (MS)
was adopted for identifying the composition of protein in sludge before and after
AD. It showed that the relative molecular weight and the isoelectric point (pI)
of the protein in the sludge decreased after AD and most of the proteins left in
the digested sludge came from the micro-organisms. These proteins cannot be
further decomposed by the microbes because of the decreased microbial metabolic
capacity at the end of the AD process or lack of specific enzymes for the
hydrolysis of these proteins. This ultimately resulted in the low decomposition
efficiency of the total protein in the sludge.
PMID- 29965637
TI - [Effect of Denitrification and Phosphorus Removal Microorganisms in Activated
Sludge Bulking Caused by Filamentous Bacteria].
AB - Activated sludge bulking or foaming caused by filamentous bacteria is a frequent
problem in the operation and management of wastewater treatment plants. To
clarify the effect of filamentous bacteria sludge bulking on the functional flora
in the biological denitrification and phosphorus removal system, morphological
identification and Illumina MiSeq sequencing were applied to investigate the
distribution of key micro-flora from the non-bulking period, sludge bulking
period, and biological foaming period in five municipal wastewater treatment
plants. The results showed that the sludge bulking and biological foaming were
caused by Microthrix parvicella when the maximum contents were 6% and 38%,
respectively. The main bacteria for denitrification and phosphorus removal were
Nitrosomonas, Nitrospira, Thauera, and Candidatus Accumulibacter phosphatis.
Compared to the non-bulking period, the relative abundance of AOB and PAO was
significantly decreased when the maximum contents were 54% and 47%, respectively,
during the bulking period. In addition, the relative abundance of denitrifying
bacteria was significantly increased when the maximum content was 73%. The
fluctuation of micro-flora for denitrification and phosphorus removal was
affected by the activated sludge bulking and was related to the treatment process
and physiological characteristics of the bacteria.
PMID- 29965638
TI - [Microbial Population Dynamics During Domestication and Cultivation of Biofilm to
Remove and Enrich Phosphate].
AB - The purpose of this study was to develop a method to remove and recover high
concentration phosphate solutions from wastewater. An experiment was carried out
to cultivate and enrich phosphorus accumulating organisms (PAOs) in the biofilm
with nylon as the biological carrier using artificial water distribution.
Microflora morphology, species diversity, and the genetic relationship of biofilm
during the process of biofilm domestication were studied by scanning electron
microscopy (SEM) and MiSeq high-throughput sequencing. In addition, the
feasibility of recycling a high concentration of phosphate in the conventional
biofilm within a short time was validated. The membrane was hung in the
biological carrier when the reactor was operated for 10 d. After the hanging of
the film succeeded, the effluent COD was below 50 mg.L-1, the effluent phosphorus
was close to zero, and the removal efficiency of phosphorus reached to above 95%.
The operation was stable at this level for 40 d. The results from the SEM
indicated that the microbial morphology in the biofilm was uniform with full oval
shaped spheres with a clear profile. MiSeq high-throughput sequencing indicated
that the dominant phylum in the reactor included Proteobacteria, Chloroflexi,
Bacteroidetes, Actinobacteria, Ignavibacteriae, and Nitrospirae. Proteobacteria,
as the dominant genera, increased from 47% to 58%. Rhodocyclaceae, as the
dominant phosphorus accumulating bacteria, increased from 17.9% to 28.9%. During
the recovery period, the concentration of the phosphorus solution increased from
40mg.L-1 to 82 mg.L-1 by increasing the influent phosphate concentration and the
COD concentration in the anaerobic phase, meeting the requirement of phosphorus
recovery with the struvite method.
PMID- 29965639
TI - [Effects of Elevated Tetracycline Concentrations on Aerobic Composting of Human
Feces: Composting Behavior and Microbial Community Succession].
AB - In order to investigate the effect of antibiotics on composting behavior,
enzymatic activity, and microbial community succession during the aerobic
composting of human feces using sawdust as the bulk carrier, tetracycline (TC)
was added to the composting system at four different concentrations (0, 100, 250,
and 500 mg.kg-1). Microbial community succession was examined by high-throughput
16S rRNA gene sequencing. The results showed that the influence of TC on the
physical and chemical properties of compost was related to its concentration.
With the increase in TC concentration, the temperature increase during aerobic
composting was inhibited, the water-soluble carbon (WSC) residue was increased,
the germination index (GI) was decreased, and the dehydrogenase activity (DHA)
was also hindered. Parameters, such as temperature, WSC, GI, and DHA, are widely
accepted and representative indicators to evaluate compost maturity. Overall,
when the concentration of TC was higher than 500 mg.kg-1, the aerobic composting
process and the maturity of the final compost were inhibited. Furthermore,
elevated TC caused significant changes in microbial community succession and
reductions in community diversity and abundance. Therefore, interference in
microbial community structures and a hindrance to biological activity are
believed to be the main adverse effects of TC on the composting process and
maturity of the composting products.
PMID- 29965640
TI - [Effect of Long-term Organic Amendments on Nitric Oxide Emissions from the Summer
Maize-Winter Wheat Cropping System in Guanzhong Plain].
AB - Agricultural soil is a significant source of nitric oxide (NO). The primary aim
of this study was to quantify the effect of long-term organic amendments on NO
emissions from the summer maize-winter wheat cropping system in Guanzhong Plain.
NO fluxes were regularly measured by the static chamber method for one year (June
2016 to June 2017). Field experiments included four fertilizer treatments that
commenced in 1990. The control (CK, 0 kg.hm-2) treatment was unfertilized
throughout the years. The fertilized treatments were synthetic fertilizer (NPK,
165 kg.hm-2), synthetic fertilizer plus maize stalk (NPKS, (165+40) kg.hm-2), and
synthetic fertilizer plus dairy manure (NPKM, (50+115) kg.hm-2) during the winter
wheat season. They were fertilized with synthetic fertilizer (188 kg.hm-2) during
the summer maize season. The results showed small NO emission [<12.2 g.(hm2.d)-1]
from the CK treatment within the experimental period. Large NO fluxes [up to
112.0 g.(hm2.d)-1 in NPK treatment] were captured following sowing and
fertilization during the summer maize season and following fertilization during
the winter wheat season for all fertilized treatments. Annual NO emissions and
direct emission factors ranged from 0.13 to 0.57 kg.hm-2 and from 0.04% to 0.12%,
respectively. Annual NO emissions from the NPKS and NPKM treatments were 17.6%
lower and 68.0% (P<0.05) larger than those from the NPK treatment, respectively.
Seasonal NO emissions from the NPKS and NPKM treatments were 41.1%-60.0% (P<0.05)
lower than those from the NPK treatment during the winter wheat season,
indicating that organic amendments reduced NO emissions. Seasonal NO emissions
from the NPKS and NPKM treatments were 25.2%-292.1% (P<0.05) larger than that
from the NPK treatment during the summer maize season, mostly due to the positive
effect of soil organic matter content on NO emissions.
PMID- 29965641
TI - [Effects of Mushroom Residue Application Rates on Net Greenhouse Gas Emissions in
the Purple Paddy Soil].
AB - China is the leading country for production of edible mushrooms and also outputs
numerous mushroom residues. The recycling of mushroom residue can solve
environmental pollution problems, provide nutrients for the farmland, and play an
important role in reducing greenhouse gas emissions and increasing soil carbon
sequestration capacity. In order to investigate the effects of mushroom residue
amounts on net greenhouse gas emissions in purple paddy soil, potted experiments
using static opaque chamber and gas chromatography methods were used to study the
changes of greenhouse gases, soil carbon sequestration, and net greenhouse gas
emissions (NGHGE) in the paddy soil with five treatments: no fertilizer (CK),
conventional fertilization (NPK), 9 t.hm-2 mushroom residue+NPK (LM), 18 t.hm-2
mushroom residue+NPK (MM), and 36 t.hm2 mushroom residue+NPK (HM) from March 2017
to September 2017.The results showed that: 1 The greenhouse gas emissions
(including CH4, CO2, and N2O) increased with increasing additions of mushroom
residue. The emissions of CH4 from highest to lowest followed: HM > MM > LM~NPK >
CK. The HM treatment significantly increased the CH4 emission flux (P<0.01) more
than the other treatments and showed an obvious single peak curve, while the CH4
emission flux with the LM treatment showed a bimodal curve, and the MM treatment
showed a multiple peak curve. The CO2 emission flux followed: MM > NPK~LM > HM >
CK; and the curves for the LM, MM, and HM treatments were a single peak curve,
bimodal curve, and multiple peak curve, respectively. The N2O cumulative emission
from the NPK treatment was significantly higher than with the other treatments.
The N2O emission flux of the NPK treatment was a bimodal curve and that of the HM
treatment was a single peak curve, while the N2O emission flux of treatments LM
and MM showed multiple peak curves. 2 The carbon sequestration capacity with the
LM treatment was lower than that of the other treatments and that from the MM
treatment was the highest. The carbon sequestration capacity of the MM treatment
increased by 59.2% compared to that of the NPK treatment and increased by 87.79%
and 65.65% compared to that of the LM and HM treatments. The LM treatment has the
highest carbon sequestration capacity, which was higher than that of the NPK and
MM treatments and about 2.1 times greater than the CK treatment and HM treatment.
3 The minimum NGHGE value was -490.29 kg.hm-2 for the whole rice production
period, and 18 t.hm-2 mushroom residue applied to the soil was the best way to
reduce net greenhouse gas emissions in purple paddy soil.
PMID- 29965642
TI - [Estimation of Winter Wheat Photosynthesized Carbon Distribution and Allocation
Belowground via 13C Pulse-labeling].
AB - Evaluating the allocation of carbon (C) photosynthesized by winter wheat
belowground is essential for C sequestration in soil and crop production. During
the four growth stages of winter wheat, i. e., tillering, elongation, anthesis,
and grain-filling, the method of 13CO2 pulse-labeling for the wheat was adopted.
Destructive samplings were undertaken at 28 d after each labeling and the total C
and 13C contents of shoots, roots, soil, and rhizosphere respiration were
determined. Results showed that the majority of the fixed 13C was recovered in
the aboveground (straw and grain), ranging from 51.6% to 90.8% in all growth
stages. The allocation of 13C photosynthesized belowground (roots, soil, and
rhizosphere respiration) decreased as the wheat growth advanced, while the 13C
transferred to the aboveground increased. Of the total 13C input belowground,
22.9%-65.3% was respired by the rhizosphere, 24.3%-59.3% remained in the roots,
and 10.4%-17.8% was incorporated into the soil organic carbon by rhizodeposition.
Respired 13C within the last 2 d of the whole chase period (28 d) only accounted
for 0.7%-2.7% of the total respired 13C, indicating that 28 days were long enough
to ensure a complete distribution of photosynthesized C within all the wheat and
soil pools. For the whole growth season of winter wheat, the photosynthesized C
allocated aboveground, to roots, soil organic carbon, and rhizosphere respiration
was 78.5%, 6.0%, 3.1%, and 12.4% of the net assimilated C, respectively. Based on
local wheat production, the total C transferred belowground was quantified as
1.72 t.hm-2, with 0.99 t.hm-2 respired as rhizosphere respiration, 0.48 t.hm-2
retained in roots, and 0.25 t.hm-2 incorporated into soil organic carbon.
PMID- 29965643
TI - [Effects of Vegetation Restoration on Soil Nitrogen Pathways in a Karst Region of
Southwest China].
AB - Nitrogen (N) is an important element for plant growth in terrestrial ecosystems.
Studying soil N cycling is crucial for understanding the structures and functions
of an ecosystem. However, our knowledge of soil N dynamics in karst regions is
still limited. In addition, while China's karst regions have conducted a series
of vegetation restoration projects, the vegetation restoration effects on soil N
pathways are still largely unknown. Therefore, this study selected four typical
ecosystems representing four main vegetation restoration stages (i. e., cropland,
grassland, shrubland, and forest) in a karst region in Huanjiang Province,
southwest China. In these ecosystems, soil N pathways, including net ammonization
rate (net ammonization, fungal ammonization, and bacterial ammonization), net
nitrification rate (i. e., net nitrification, heterotrophic nitrification,
autotrophic nitrification, fungal nitrification, and bacterial nitrification),
net N mineralization rate (net N mineralization, fungal mineralization, and
bacterial mineralization), and soil properties were measured. Our results showed
that nitrification rate was high in all ecosystems, but the ammonization rate was
low, resulting in nitrite being the main inorganic N form in karst soil.
Autotrophic and heterotrophic nitrification rates accounted for 80% and 20% of
the net nitrification rate, respectively. After the addition of fungal and
bacterial inhibitors, ammonization rates increased for all treatments, but the
nitrification rates decreased. Following vegetation restoration, soil N
mineralization and nitrification rates all increased, but the ammonization rates
significantly decreased. This pattern was significantly correlated with soil
organic carbon, total nitrogen, nitrate, microbial biomass, and the activity of N
acquisition enzymes in these ecosystems. Our findings provide very useful
information for understanding soil N cycling in the karst regions.
PMID- 29965644
TI - [Identifying the Origins and Spatial Distributions of Heavy Metals in the Soils
of the Jiangsu Coast].
AB - A total of 239 samples of surface soils were collected along the Xiangshui to
Rudong coast, in Jiangsu Province, and analyzed for Cd, Cr, Cu, Hg, Ni, Pb, and
Zn. A multivariate analysis was applied to identify the sources of heavy metals,
and ordinary kriging was used to map the spatial distributions of the heavy metal
concentration. The mean contents of Cd, Cu, Hg, Pb, and Zn in the surface soils
of the Jiangsu Coastal Zone were higher than the background values of the Jiangsu
Coastal Plain, which indicated that there were obvious accumulations of these
heavy metals in surface soils; while the mean contents of Cr and Ni were lower
than the background values. The contents of Cd, Cr, Cu, Pb, Ni, and Zn in soils
that originated from marine deposition were significantly lower than those from
alluvium and lagoon facies deposition, including the Yangtze River Delta
deposition. Urban areas exhibited higher Cd, Cu, Hg, Pb, and Zn contents than
other land covers. Cr and Ni were controlled by the parent material and seemed to
originate from a natural source. Cd, Cu, Pb, and Zn were associated with the
combination of parent material and anthropogenic inputs. Hg was dominated by
atmospheric deposition related to various human activities. The high values of
Cd, Cu, Pb, and Zn were distributed in the northern, western, and southern parts
of the study area, and Hg exhibited high values around the urban areas in the
western and southern parts.
PMID- 29965645
TI - [Source Identification and Spatial Distribution of Heavy Metals in Soils in
Typical Areas Around the Lower Yellow River].
AB - A total of 234 surface soil samples (0-20 cm) were collected at the nodes of a
2*2 km grid from Gaoqing County (a typical area surrounding the Lower Yellow
River) and analyzed for eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn).
This study investigated the source of the heavy metals in this area based on a
correlation analysis, PCA, and ANOVA using multivariate statistical analysis. In
addition, the spatial variation and distribution characteristics of the heavy
metals were determined by geostatistics based on GIS. The results provided the
following conclusions. 1 The mean concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb,
and Zn exceeded the background values (BV) of the Lower Yellow River, especially
for As, Cu, and Hg (1.23, 1.20 and 1.29 times the BV, respectively), indicating
that there was enrichment of the heavy metals in soils at different degrees. 2
The results from the multivariate analysis suggested that all eight heavy metals
could be classified by two principal components (PCs). The levels of As, Cd, Cr,
Cu, Ni, Pb, and Zn were dominated by human activities and the parent soil
material (PC1). However, Hg originated mainly from textile printing,
petrochemical engineering, and plastic processing (PC2). 3 The differences in
heavy metal contents between different land use types and parent soil materials
were obvious. The eight elements were highest in land related to urban
construction. In addition to Hg, the remaining seven heavy metals were highest in
soils in the lacustrine deposit. 4 The spatial distributions of the heavy metals
in the soil were different. The high value areas of As, Cd, Cr, Cu, Ni, Pb, and
Zn were mainly concentrated in the central urban and southeastern areas, while
the high value areas for Hg were concentrated in the southwestern and
northeastern areas. This showed that industrial emissions and agricultural
production activities caused the degree of heavy metal pollution in the soils
while traffic emissions aggravated the levels.
PMID- 29965646
TI - [Spatial Variation of Soil Heavy Metals in Lin'an City and Its Potential Risk
Evaluation].
AB - Urban soil is an important part of the urban ecosystem, which is strongly
correlated with human health and life quality. In this study, Lin'an city was
chosen as a typical small city to study the spatial variation and distribution of
heavy metals in urban soils and their pollution characteristics using
multivariate analysis, geostatistics, and GIS techniques. A total of 62 soil
samples were collected from the study areas. The results indicated that the
average concentrations of soil Mn, Cu, Zn, Pb, Cr, and Cd were 439.42, 42.23,
196.80, 62.55, 63.65, and 0.22 mg.kg-1, respectively. Compared with the
background values and the environmental quality standards, these heavy metals
were accumulated in urban soils to some extent. Almost 80% of the study area was
polluted by heavy metals. The single potential ecological risk index of heavy
metals indicated that Pb had the highest ecological risk. The pH and most of the
heavy metals had strong correlations, and there were strong correlations among
the heavy metals. The principle component analysis (PCA) showed that Pb, Zn, and
Cu had the same pollution source, which was related to vehicle exhausts; Mn and
Cr were mainly from the parent material; and Cd was from the emissions of
manufacturing plants. The spatial structure and distribution of heavy metals and
their corresponding available fractions had strong spatial autocorrelation with
all of the C0/(C0+C)<50%. Their spatial patterns were influenced by human
activities.
PMID- 29965647
TI - [Principal Component Analysis and Ecological Risk Assessment of Heavy Metals in
Farmland Soils around a Pb-Zn Mine in Southwestern China].
AB - The farmland soil around a Pb-Zn mine in southwestern China was studied. One
hundred forty-nine surface soil samples were taken from 0-20 cm depth, and the
contents of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn were tested. The correlations
among these heavy metals were studied with multivariate analysis, and the
potential sources of the metals were identified. The environmental risk of the
metals was evaluated with the Potential Ecological Risk Index method. The results
showed that the amounts of Cd, Pb, and Zn were at relatively high level, with
average concentrations of 15.56, 419.4, and 933.4mg.kg-1 respectively, indicating
the soil was heavily polluted. The average concentrations of Hg and As were 0.13
and 37.3mg.kg-1, suggesting moderate soil pollution. The average concentrations
of Cu, Ni, and Cr were lower than Yunnan soil background values. The multivariate
analysis suggested that the sources of Cd, Pb, Zn, Hg, and As were similar and
came mainly from smelting activities in the mining area. The sources of Cu, Ni,
and Cr were similar and can be attributed to natural sources. The comprehensive
potential ecological risk index was 2294.8, which suggested a high potential
ecological risk. In general, the farmland soils in the research area were
polluted seriously by the mining and industrial activities.
PMID- 29965648
TI - [Spatial Variation of Heavy Metals in Soils and Its Ecological Risk Evaluation in
a Typical Carya cathayensis Production Area].
AB - In recent years, the problem of soil pollution has become more and more serious.
The problem of soil heavy metal pollution and its related human health risks has
become a hot spot at home and abroad. Carya cathayensis is a unique high-grade
woody nut and oil tree from China, and there are few reports on heavy metal
pollution in Carya cathayensis plantation soils. Therefore, in order to study the
spatial variability of heavy metals and the risk of pollution in Carya
cathayensis soil and to promote the sustainable development of the Carya
cathayensis industry, Lin'an, a typical Carya cathayensis plantation area, was
selected for this study. A total of 188 soil samples were collected from the
study area. We systematically studied the spatial heterogeneity of soil heavy
metal content in the study area based on GIS technology, geostatistics, Moran's
I, and other spatial analysis methods. The single factor pollution index method,
the Nemerow comprehensive pollution index method, and the potential ecological
risk assessment method were used to evaluate the heavy metal pollution in the
study area. The results indicated that the mean content of soil cadmium (Cd),
copper (Cu), zinc (Zn), lead (Pb), nickel (Ni), and chromium (Cr) were 0.37,
40.76, 87.61, 30.10, 28.33, 56.57 mg.kg-1, respectively. The average values of Cd
and Cu were 1.33 and 2.87 times of the background values, respectively, and the
average content of other heavy metals did not exceed the background values. The
results of the single factor Nemerow pollution index and potential ecological
risk assessment methods showed that heavy metals in the study area exceeded the
soil background values in some samples, and the second grade standard of soil
environmental quality was exceed for Cd, Cu, Zn, Pb, and Ni in 31.38%, 31.38%,
2.65%, 0.53%, and 17.02% of the samples, respectively. This indicated that the
soils in the study area had different accumulation characteristics for Cd, Cu,
Zn, Pb, Ni, and Cr, and the local soil had reached pollution levels for Cd, Cu,
Zn, Pb, and Ni. Among them, Cd was the most serious, reaching the degree of
strong ecological damage, followed by Cu. In general, the heavy metal contents
indicated a moderate degree of ecological damage. Based on the analysis of the
semi-variance function, the Cd, Cu, and Ni in the soil were best fit with
exponential models, the Zn and Pb were better fit with the Gaussian model, and Cr
was consistent with the spherical model. Cd, Cu, Pb, Ni, and Cr had the strong
spatial autocorrelation, with Nugget/Sill ratios of 12.1%, 4.6%, 14.9%, 2.6%, and
11.2%, respectively, while the Nugget/Sill ratio of Zn was 48.8%, indicating a
medium spatial autocorrelation. Moran's I and Kriging interpolation results found
that the heavy metals Cd, Cu, Zn, Pb, Ni, and Cr all had obvious spatial
distribution patterns and local spatial aggregation phenomena. The high values of
heavy metals in soils were mainly found in Taiyang, Daoshi, Qingliangfeng,
Heqiao, and Tuankou, and the probability of the risk for contamination by Cd and
Cu was higher in the study area. The high values of Cd, Cu, Zn, Ni, and Cr were
mainly related to mining, while Pb was closely related to the application of
potassium.
PMID- 29965649
TI - [Influence of Biochar Application on Growth and Antioxidative Responses of
Macrophytes in Subsurface Flow Constructed Wetlands].
AB - Constructed wetlands (CWs) have high potential for wastewater treatment in
developing countries because of their operational convenience and low maintenance
costs. However, rapid accumulation of macrophytes in these wetlands, as a result
of plant litter recycling, can lead to lower removal efficiencies. Periodic
harvesting is consider to be the effective measure to maintain the wastewater
treatment performance, and so a lot of harvested plant waste needs to be properly
disposed of. However, in China, plant waste is usually used for agricultural
burning and the greenhouse gas emissions bring adverse effects on the atmospheric
environment. In the traditional subsurface flow CW, the dissolved oxygen (DO)
concentration is low, resulting in long-term anoxic or anaerobic conditions,
which will bring damages to plant body, such as membrane lipid peroxidation and
protein and DNA damage. Generally, the addition of biochar to CWs is beneficial
for aeration, and improves the internal environment of wetlands. Hence, the
effects of plant biochar on the pollutant purification efficiencies in CWs were
studied, and the role of biochar in macrophyte growth and antioxidative response
was investigated. Based on the results of biochar application in agricultural
fields, the harvested wetland plant straw was pyrolyzed to biochar at 500 C under
a dynamic high-purity nitrogen atmosphere. The wetland plant Acorus calamus L.
(AC) was chosen for this study. The impact characteristics of biochar on AC were
studied in five independent CWs built in a greenhouse, by combining the analyses
of growth and antioxidative responses of plants. Results showed that the removals
of ammonium (NH4+-N) and total nitrogen (TN) were significantly enhanced when
biochar was added to CWs and that higher long-term nitrogen removal rates were
achieved when the biochar application rate was increased. The photosynthetic
pigment content in AC increased significantly with increasing biochar application
rate. This stimulated photosynthesis and increased the soluble protein (SP) and
plant biomass amounts. Further, glutamine synthetase (GS) activity was
strengthened with the addition of biochar. This helped enhance the NH4+-N
metabolism and increased the relative uptake rate of AC. This study confirmed
that long-term anoxic or anaerobic conditions in CWs cause membrane lipid
oxidation in plants. However, the activity of the antioxidative response system
was promoted with the addition of biochar, significantly decreasing the malonic
dialdehyde (MDA) content in the plants.
PMID- 29965650
TI - [Effect of Iron on the Release of Arsenic in Flooded Paddy Soils].
AB - Amorphous iron oxides in paddy soil are critical adsorbents of arsenic. The
flooding period during rice cultivation contributes to the reductive dissolution
of these amorphous iron oxides, which releases sorbed arsenic into the paddy soil
solution. However, more detailed work should be conducted to evaluate
quantitatively arsenic immobilization, release, and transformation regulated by
metastable amorphous iron oxides. In previous studies, arsenic in the soil
solution phase and solid phase were classified into F1 (exchangeable arsenic), F2
(specifically sorbed arsenic), F3 (amorphous iron oxide bound arsenic), and F4
(crystalline iron oxide bound arsenic), according to a sequential extraction
procedure using reagents of increasing dissolution strength. In this study, soil
samples were collected from the vicinity of a silver smelting plant in Chenzhou,
Hunan Province, and the contribution of different arsenic speciation (F1, F2, F3,
and F4) to arsenic release during anaerobic enrichment incubation of paddy soil
was investigated. Sample analysis was conducted at the end of the first phase
(day 15) and the second phase (day 30). The effects of amorphous iron oxides in
paddy soil on migration and transformation of arsenic were discussed. Results
showed significant elevation of dissolved Fe(II) and arsenic concentration
(P<0.05) in enrichment solutions in the second phase compared with that in the
first phase. Arsenic released in the soil solution in both phases originated from
exchangeable arsenic and specifically sorbed arsenic, as indicated by its
significantly positive correlation with F1 and F2 (r=0.73, P<0.05; r=0.657,
P<0.05). However, an insignificant positive correlation was found between the
arsenic released and F3. Moreover, HCl-extractable Fe(II) was significantly and
positively correlated with arsenic (r=0.577, P<0.05; r=0.613, P<0.05), while
amorphous iron oxides were significantly and negatively correlated with arsenic
(r=-0.428, P=0.126; r=-0.564, P<0.05). In conclusion, arsenic in the F1 and F2
fractions acted as the major source of released arsenic. Despite elevated levels
of HCl-extractable Fe(II) that might result from the slight reductive dissolution
of amorphous iron oxide, the significant negative correlation between dissolved
arsenic and amorphous iron oxides indicated that metastable amorphous iron oxides
in anaerobic paddy soil can generally sorb dissolved arsenic effectively,
resulting in lower mobility of arsenic. Increasing the level of amorphous iron
oxides in paddy soil is conducive to inactivation of arsenic.
PMID- 29965651
TI - [Concentrations and Health Risk Assessments of Heavy Metal Contents in Soil and
Rice of Mine Contaminated Areas].
AB - Nandan County is famous for its mining of nonferrous metals. In order to
investigate the effects of mining activities on the soil and rice and to evaluate
the health risk of the exposure of typical local inhabitants to heavy metals via
consumption of rice, a consecutive 3-day household diet survey in four villages
in Nandan was conducted. Liuzhai is an uncontaminated contrast area, and Chehe,
Dachang, and Zhanglao are contaminated areas. The data for rice consumption rates
were obtained. At the same time, 56 soil samples from rice fields and 90 rice
samples were collected for the analysis of As, Sb, Cd, Pb, Cu, and Zn. In
addition, the potential health risk of the exposure of local people to heavy
metals via consumption of the rice was assessed using the pollution index method
and the data from the intake of heavy metals. Results showed that the mean
contents of As, Sb, Cd, Pb, Cu, and Zn were 58.1, 16.4, 1.22, 49.1, 52.1, and 271
mg.kg-1 in the soil samples from contaminated areas, with higher pollution risks
than from the control area for soil heavy metal contents. The Nemero
comprehensive contamination index (PN) was 3.14, a heavy pollution grade. Cd
contents in rice in Liuzhai, Chehe, Dachang, and Zhanglao were 2.23 times, 4.40
times, 3.81 times, and 3.52 times higher than those of GB 2762-2017.The content
in rice exceeds the standard in all four areas. The daily intake (DI) of Cd in
the four areas was higher than the provisional tolerable daily intake (PTDI)
established by FAO/WHO. This indicates that Cd and As are the major heavy metal
elements posing health risks to the health of the inhabitants in the mining areas
and that the inhabitants in the mining areas are facing severe risks of exposure
to heavy metals.
PMID- 29965652
TI - [Effect of Calcium Silicate-biological Humus Fertilizer Composite on Uptake of Cd
by Shallots from Contaminated Agricultural Soil].
AB - The safety of vegetable production is a key link in reducing cadmium consumption
through the food chains. Field experiments were conducted to investigate the
effects of composite materials (calcium silicate-biological humus fertilizer) on
the growth of shallots and the uptake of Cd by shallots from contaminated
agricultural soil. Four treatments (T1: 0.5% calcium silicate+0.5% biological
humus fertilizer; T2: 0.5% calcium silicate+1.0% biological humus fertilizer; T3:
1.0% calcium silicate+0.5% biological humus fertilizer; and T4: 1.0% calcium
silicate+1.0% biological humus fertilizer) and a control group (CK) were adopted.
The changes in soil pH, DTPA-extractable Cd, biomass of shallots, and cadmium
concentrations in shallots over time under different treatments were analyzed.
The results show that the application of composite amendments decreased the
concentrations of DTPA-extractable Cd in the soil. In particular, after T3
treatment, the concentrations of soil DTPA-extractable Cd decreased by 60.71%,
49.54%, 44.63%, and 58.94% after 14, 28, 42, and 56 d, respectively. The biomass
of the shallots aboveground increased significantly by 107.99% and 107.19% after
T3 and T4 treatment, respectively. The composite amendments exhibited different
effects on the uptake of Cd by the shallots from the soil, and the T4 treatment
was the most effective in immobilizing Cd and inhibiting translocation of Cd into
the shallots. The cadmium concentration in the shallots decreased by 43.80% after
56 d with the T4 treatment. In conclusion, T4 is the optimum treatment for soil
cadmium immobilization.
PMID- 29965653
TI - [Accumulation Characteristics of Heavy Metals in Greenhouse Soil and Vegetables
in Siping City, Jilin Province].
AB - Based on the typical greenhouse vegetable production system in Siping City, Jilin
Province, 124 soil samples were collected from greenhouse soils growing
vegetables (GSGV), fields growing maize (FGM), and forest soil (FS) under
different land utilization patterns. In addition, other samples including
greenhouse vegetables (81), fertilizers (50), and irrigation water (10) were also
collected in the studied region. To illustrate the accumulation characteristics
of heavy metals in GSGV and greenhouse vegetables, the heavy metal content of
different samples was measured using inductively coupled plasma mass spectrometry
(ICP-MS) technology. The results indicated that the heavy metal content in GSGV
was much higher than that in FGM and FS except for lead (Pb). Heavy metals
including cadmium (Cd), copper (Cu), chromium (Cr), nickel (Ni), and zinc (Zn) in
GSGV presented with various degrees of accumulation. The mean value of Cd content
in the soils in the investigation region was 0.45 mg.kg-1, with about 42.8% of
all the soil samples exceeding the Cd content criterion of the Environmental
Quality Evaluation Standard for Farmland in Greenhouse Vegetable Production (HJ
333-2006). The content of the other heavy metals was in the normal range, and all
met the regulations of the standard. In comparison with different vegetable
categories, leafy vegetables showed much higher heavy metal concentrations (Cd
0.033 mg.kg-1 fresh weight) than did fruity ones. In total, about 2.5% and 1.2%
of vegetable samples exceeded the regulated values of Cd and Pb recommended by
the Standard of Food limits, respectively. With the cultivation time prolonged,
heavy metal concentration in soils and vegetables all increased synchronously as
the pH value decreased. The content of heavy metals in greenhouse vegetables was
significantly influenced by soil pH and organic matter. It can be concluded that
the health risk of greenhouse vegetables increased with GSGV accumulating more
heavy metals due to the substantial application of chemical fertilizer and manure
containing high level of heavy metals.
PMID- 29965654
TI - [Effect of Foliar Zinc Application on Bioaccessibility of Cadmium and Zinc in
Pakchoi].
AB - Two cultivars of pakchoi with different cadmium (Cd) accumulation were grown in
nutrient solutions containing low and sufficient zinc (Zn) levels. ZnSO4 and
ZnNa2 EDTA were applied as foliar fertilizers. The bioaccessibilities of Cd and
Zn in pakchoi were assessed by the in vitro digestion method, and the
bioaccessible established daily intakes (BEDI) of Cd and Zn from pakchoi were
calculated. The effect of foliar zinc application on concentrations,
bioaccessibilities, and BEDIs of Cd and Zn in pakchoi was evaluated. Results show
that the Cd concentrations in shoots of the tested pakchoi cultivars under
sufficient Zn condition were significantly lower than those under low Zn
condition, and foliar application of ZnNa2 EDTA significantly decreased the Cd
concentrations of pakchoi. The tested pakchoi cultivars with sufficient Zn had a
significantly higher mean shoot Zn concentration than those with low Zn. Foliar
Zn treatments significantly increased shoot Zn concentrations of pakchoi, with
the highest in the ZnSO4 treatment. Cd bioaccessibility in the tested pakchoi
cultivars with sufficient Zn was significantly lower than that with low Zn.
Foliar applied Zn could significantly reduce Cd bioaccessibility in the gastric
phase, with a maximal reduction of 35.81% compared to the control. Foliar
treatment with ZnSO4 could significantly decrease Cd bioaccessibility in the
small intestinal phase, with a maximal reduction of 59.24% compared to the
control. Foliar Zn treatments reduced significantly the Zn bioaccessibility of
pakchoi in the gastric and small intestinal phases, with a maximal reduction of
68.90% compared to the control. The reduction of Zn bioaccessibility was higher
in the ZnSO4 treatment than in the ZnNa2 EDTA treatment. Via the consumption of
the Cd-contaminated common cultivar Hanlv, the BEDI values of Cd were higher than
that of the provisional tolerable daily intake (PTDI) standard of WHO [0.83
MUg.(kg.d)-1]. However, via the consumption of the low-Cd accumulating cultivar
Huajun or pakchoi with foliar application of ZnSO4, the BEDI values of Cd
decreased significantly and were below the PTDI value. Via the consumption of
pakchoi in the control or low-level ZnNa2 EDTA treatments, the BEDI values of Zn
were below that of the recommended nutrient intake for Zn. However, via the
consumption of pakchoi with foliar application of ZnSO4 or high-level ZnNa2 EDTA,
the BEDI values of Zn were higher than that of the recommended nutrient intake
and met the human needs for Zn from vegetables. Under the ZnSO4 treatment, the
BEDI values of Zn from pakchoi were the highest. In conclusion, foliar zinc
application could significantly reduce the bioaccessibilities of Cd and Zn in
pakchoi and the BEDI values of Cd and increase the BEDI values of Zn. Foliar
application with ZnSO4 was the most suitable treatment to reduce Cd intake and
increase Zn intake from pakchoi.
PMID- 29965655
TI - [Mercury Distribution of Benthonic Animals and Response to Mercury in Sediments
in Caohai Wetland, Guizhou Province].
AB - Caohai wetland is a National Nature Reserve. Benthic animals were collected from
the deep-water area in the middle of Caohai Lake and the shallow-water area in
the surrounding marshes, and mercury and methyl mercury distributions in the
benthic animals were analyzed and discussed. The risk of mercury pollution was
evaluated. The concentrations of total mercury and methyl mercury in the
benthonic animals were in the range of 0.51-46.55 ng.g-1 with an average of 7.82
ng.g-1 and 0.04-27.71 ng.g-1 with an average of 4.31 ng.g-1, respectively. This
was lower than reports from other natural reserves. By contrast, the total
mercury and methyl mercury in the benthic animals in summer were higher than in
other seasons, which was consistent with the characteristics of methyl mercury
distribution in sediments but opposite to the spatial distribution
characteristics of total mercury in sediments. The methyl mercury contents in
Cipangopaludina cathayensis were positively correlated with the content of methyl
mercury in the sediments (r=0.52, P<0.05). The results showed methylation and the
bioavailability of mercury in sediments from the shallow-water area were
obviously higher than those from the deep-water area in the middle of Caohai
Lake. The difference in organic matter content of the sediment or the wet-dry
alternation (flooding-receding-flooding) in the surrounding shallow marshes was
suspected to be associated with the obvious difference. The high enrichment
coefficient of total mercury and methyl mercury in benthic animals were
sufficient to raise the risk of mercury contamination in the aquatic food chain
in the wetland.
PMID- 29965656
TI - [Discussion of Emissions and Health Risk of Polycyclic Aromatic Hydrocarbons
(PAHs) from the Retreading Process of Waste Tires].
AB - The emissions characteristics of 16 kinds of polycyclic aromatic hydrocarbons
(PAHs) in ambient air during the waste tire retreading process (open-air storage,
mixing, vulcanization, and grinding processes) and in workers' dormitory were
analyzed. In addition, the occupational health risk of the workers was evaluated.
Results showed that PAHs were detected in all retreading processes and in the
workers' dormitory. The highest concentration site was the mixing process,
followed by open-air storage and vulcanization process. The lowest concentration
point was in the grinding process. The average concentration of PAHs in the
workers' dormitory was 11.1 ng.m-3. The PAHs at all sampling points were largely
phenanthrene (Phe), fluoranthene (Flu), anthracene (Ant), and pyrene (Pry), which
also had a stronger linear correlation with the total PAH concentration. An
analysis of the benzene rings showed that three ring and four ring were the
majority, while two ring, five ring, and six ring components accounted for less
than 10%. Results of the possible influencing factors of the PAHs revealed that
the open-air storage and dormitory might be affected by a combustion source, but
the mixing, vulcanization, and grinding processes might be affected by rubber
oil. The principal component analysis (PCA) and cluster analysis showed that the
spatial location of all sites would significantly influence the distribution of
PAHs during the tire retreading process. The health risk assessment showed that
occupational workers had a lower risk of lifelong cancer, and there was little
influence on life expectancy.
PMID- 29965657
TI - [Spatiotemporal Dynamics of CO2 Emissions in Chongqing: An Empirical Analysis at
the County Level].
AB - China's CO2 emissions present obvious temporal and spatial distribution
characteristics. Therefore, the study of spatiotemporal dynamics of CO2 emissions
could provide useful information for the government and policy-makers on viable
CO2 emissions mitigation in China. Using Chongqing as a case study, we
investigated the spatiotemporal dynamics of CO2 emissions at the county level (38
counties) from 1997 to 2012.The mathematical statistical method, spatial
autocorrelation, and rank size rule were employed to evaluate the CO2 emissions
change in detail. The results showed that all of the counties in Chongqing have
experienced a rapid growth of CO2 emissions, but the two dimensional structure of
CO2 emissions has not changed. The Global Moran's I clearly decreases with a
small fluctuation, and these values gradually decrease from 0.56 in 1997 to 0.40
in 2012.In addition, the HH clusters are concentrated in some counties in the
downtown areas. Based on the rank size rule analysis, the slope values q decrease
from -1.35 in 1997 to -0.88 in 2012, indicating a clear scattered pattern of CO2
emissions in Chongqing at the county level. It has also been proven that the
proportion of second industries and the urbanization rate are more important
impact factors for CO2 emissions than the population.
PMID- 29965658
TI - [Impact of Size on Environmental Behavior of Metal Oxide Nanoparticles].
AB - With the rapid development of nanotechnology, the environmental behavior and
ecological effect of nanoparticles (NPs) are receiving more and more attention.
As an important environmental component, metal oxide NPs occur widely in nature,
such as in water bodies, air, soils, and sediments. They have a large surface
area and high surface activity, allowing them to control and affect the
speciation, migration, transformation, and bioavailability of some contaminants
and nutrients in the environment. The nano-size is a unique property of
nanoparticles. The size of particles regulates and determines the structure and
physicochemical properties of nano-oxides, which greatly affects interfacial
reactions with the relevant elements and environmental geochemical behaviors. The
effects of NPs size on the environmental geochemical behaviors, such as
adsorption, (reductive) dissolution, (catalytic) oxidation, aggregation and
transport, are briefly summarized, and the mechanism of the size effect is
discussed. Finally, hot spots for future research of metal oxide nanoparticles
related to size effects in the environment are proposed.
PMID- 29965659
TI - [Fate and Toxicity of UV Filters in Marine Environments].
AB - UV filters have been widely used in sunscreen products, and they have partially
ended up in the marine environment via human recreational activities and sewage
treatment plant drainage, becoming one of the emerging marine pollutants. As UV
filters have many characteristics, such as extensive use, continuous emissions,
and stability, their potential risks to the environment and ecology have become a
hot topic in the field of environmental research all over the world. This study
analyzed the environmental behavior of UV filters in the ocean, such as
migration, transformation, and volatilization. The toxic effects (i. e., growth
inhibition, reproductive inhibition, death, and malformation) of the inorganic
(mainly nano-TiO2 and nano-ZnO) and organic UV filters (mainly benzophenones,
camphor derivatives, and cinnamic acids) on marine organisms (i. e., algae,
seashell, fish, coral, and sea urchin) were summarized. The research also
analyzed the inherent toxicity mechanisms from the perspective of oxidative
damage, neurotoxicity, and endocrine disability. The prospect and future
directions in this field were also discussed. This review provides a reference
for scientific research and pollution control related to UV filters.
PMID- 29965661
TI - [Source Apportionment of Black Carbon Aerosol in the North Suburb of Nanjing].
AB - Based on one year real-time measurements from a seven-wavelength Aethalometer
combined with an Aethalometer model, the measured aerosol absorption coefficients
at different wavelengths have been used to apportion the contribution of fossil
fuel and biomass burning sources to the total black carbon (BC) mass
concentration in the north suburb of Nanjing. Good consistency in the
relationship between the Angstrom absorption exponent(alpha)and the ratio of BC
from biomass burning sources to total BC (BB) was obtained during this period.
The alpha was highest in winter and lowest in summer, which indicates the change
in the source of the absorbing aerosols and their relative source strength. The
BC and the BC from fossil fuel (BCff) and biomass burning (BCbb) mass
concentrations exhibit significant diurnal variation, with higher values during
07:00 to 09:00 (local time) and 18:00 to 21:00. The BCff was three to five times
higher than the BCbb and contributes greatest to the BC mass concentrations
throughout the day. Night time BC values were about a factor of 1.2 higher than
day time BC values. Meanwhile, the concentration weighted trajectory (CWT)
analysis indicates that the highest value of BC was concentrated in the Zhejiang,
Anhui, Jiangxi, and Fujian provinces.
PMID- 29965660
TI - [Variation of O3 Concentration in Different Regions of Beijing from 2006-2015].
AB - O3 continuous monitoring data for the Dingling, Guanyuan, Liulihe, and Qianmen
sites from 2006-2015 were analyzed to investigate concentration levels, variation
trends, temporal variations, and relationships with precursors and meteorological
factors. The results showed that the ten year average concentrations of O3 at the
Dingling site were the highest at 65.2 MUg.m-3, followed by concentrations at
Liulihe (53.4 MUg.m-3), Guanyuan (49.6 MUg.m-3) and Qianmen (40.4 MUg.m-3). The
O3 concentrations at Dingling showed a decreasing trend[0.5 MUg.(m3.a)-1], while
O3 concentrations at Guanyuan[0.9 MUg.(m3.a)-1], Liulihe[0.3 MUg.(m3.a)-1], and
Qianmen[0.3 MUg.(m3.a)-1] showed an increasing trend. The highest monthly average
concentrations appeared during June and August, and the highest frequency
occurred in July (17 times) with average concentrations of 99.8 MUg.m-3. The
lowest monthly average concentrations appeared during November and February, and
the highest frequency occurred in January (14 times) with an average
concentration of 16.6 MUg.m-3. Notably, the time for the peak concentrations of
O3 appeared earlier in the day in recent years. The peak concentrations of O3
appeared at 15:00-16:00 during 2013-2015, which was 1-2 hours earlier than
previous years. The heavy air pollution of O3 occurred on 11 days at the Dingling
site in 2015, which was ten days more than in 2013, indicating O3 pollution in
the downwind suburban regions of Beijing in summer became more and more serious.
The concentrations of O3 and NO2 at Dingling showed a positive correlation, while
the concentrations of O3 and NO2 at the other sites showed a negative
correlation, indicating O3 formation in Dingling was sensitive to NO2 chemistry,
while O3 formation at the other sites was sensitive to VOC chemistry. The
concentrations of O3 showed a positive correlation with temperature and negative
correlations with humidity and surface pressure. Temperature had the greatest
influence on O3 concentration, followed by surface pressure and humidity. For
cases when daily maximum temperature exceeded 30C and relative humidity was
between 30% and 70%, the probability of the O3 daily maximum 8 h concentration
exceeding 200 MUg.m-3 was high, indicating the air quality level reached levels
for light pollution and moderate pollution.
PMID- 29965662
TI - [Seasonal Characteristics and Ecological Risk Assessment of Heavy Metals in PM10
Around Electroplating Plants].
AB - PM10 samples were collected from 45 sites around the electroplating factories in
five towns in Dongguan at different times during all four seasons in 2015. The
contents of 12 heavy metals (HMs) from the PM10 samples were analyzed by ICP-MS.
The seasonal and spatial distribution characteristics and the ecological risk
were analyzed to provide a scientific foundation for the relevant department to
make decisions regarding the environmental hazard, risk assessment and, pollution
control. The results showed that PM10 concentrations in the towns were lower than
national standard level-II, and the air pollution was heavier in winter than
summer. The HM concentrations were higher in autumn and winter, and As, Cd, and
Cr concentrations were higher than national standard (GB3095-2012). The
concentrations of HMs in Humen, Shatian, and Dalingshan were much higher. The
results for the enrichment factor and the geoaccumulation index indicated that
Cd, Sb, Hg, and Co were in the extreme degree of pollution category, Pb and Zn
were in the slight to extreme degree of pollution category, and Ni, Cr, Mn, and V
were described as uncontaminated. The average potential ecological risk
assessment (RI) of the HMs from the PM10 samples was more than 600, which
suggested an extremely serious ecological risk in the study area.
PMID- 29965663
TI - [Characteristics of Organic and Elemental Carbon in PM10 and PM2.5 in Yulin City,
Guangxi].
AB - Two hundred eighteen PM10 and 202 PM2.5 samples were collected at three sampling
sites to study the pollution characteristics of carbonaceous aerosols in Yulin
from July 2015 to March 2016. Organic carbon (OC) and elemental carbon (EC) in
the PM10 and PM2.5 samples were analyzed by a Multiwavelength Thermal/Optical
Carbon Analyzer, and the characteristics, including pollution levels, temporal
and spatial distributions, and possible sources of OC and EC, were investigated.
The results showed that the OC and EC mass concentrations in PM10 in Yulin were
10.99 and 5.11 MUg.m-3, respectively, while the OC and EC mass concentrations in
PM2.5 were 7.51 and 4.70 MUg.m-3, respectively. Strong correlations between OC
and EC were found in PM10(R2=0.58) and PM2.5(R2=0.60). The winter average
concentrations of secondary organic carbon (SOC) in PM10 and PM2.5 were 14.50
MUg.m-3 and 6.74 MUg.m-3, respectively. The SOC/OC ratios in both the PM10 and
PM2.5 were higher than 0.5. The contribution of SOC to OC was 80.6% in PM10 and
77.7% in PM2.5, which were the highest in the summer, in accordance with the high
temperature and strong solar radiation in the summer.
PMID- 29965664
TI - [Concentrations and Compositions of Different Forms of Nitrogen and Phosphorus in
Atmospheric Aerosols in the Qingdao Coastal Region and over the Yellow and Bohai
Sea].
AB - The total suspended particulate (TSP) samples were collected in the Qingdao
coastal region and over the Yellow and Bohai Sea from June to July in 2016. The
diurnal and nightly TSP samples were also continuously collected in the Qingdao
coastal region from August 6 to 15. The concentrations of dissolved inorganic
nitrogen (DIN), dissolved inorganic phosphorus (DIP), dissolved total nitrogen
(DTN), dissolved total phosphorus (DTP), total nitrogen (TN), and total
phosphorus (TP) in the TSP samples were analyzed. Results showed that the
concentrations of different forms of nitrogen and phosphorus in Qingdao were
higher than those over the Yellow and Bohai Sea during the same sampling period.
The contribution of dissolved N was similar to that of insoluble N to TN in
Qingdao, with the ratio of DTN to TN of 56%. However the DTN was the dominant
contributor of TN over the Yellow and Bohai Sea, accounting for 72% of TN on
average. The inorganic nitrogen was the dominant species of DTN in Qingdao and
over the Yellow and Bohai Sea (YBS), accounting for 67% and 75% of DTN,
respectively. The contribution of dissolved P to TP was similar to that of
insoluble P to TP in Qingdao and over the Yellow and Bohai Sea, and the DTP
accounted for 49% and 58% of TP in Qingdao and over YBS, respectively. The ratio
of IP to DTP was slightly higher than that of OP, with values of 56% and 59% in
Qingdao and over the YBS, respectively. The origin of the air mass affected the
concentrations and compositions of nitrogen and phosphorus in the aerosols. The
concentrations of DIN, dissolved organic nitrogen (DON), TN, DIP, and dissolved
organic phosphorus (DOP) in the aerosols from southern air mass were higher than
those from northern and marine air masses. The concentration of DON in the
diurnal aerosol samples was similar to that in the nightly samples; however, the
concentrations of DIN and TN were higher in the diurnal aerosols than those in
the nightly aerosols. The DTN was the dominant species of TN in the diurnal and
nightly aerosol samples, accounting for 79% of TN on average. Inorganic nitrogen
was the dominant species of DTN in the diurnal and nightly aerosols. The ratio of
DIN to DTN decreased from 70% in diurnal samples to 61% in nightly samples. The
concentrations of DIP were close to that of DOP in the diurnal and nightly
aerosols; however, the concentrations of TP were higher in the diurnal aerosols
than in the nightly ones. The insoluble P was the dominant form of TP in the
aerosols, accounting for 83% and 62% of TP during the day and night,
respectively. The contribution of DTP to TP in the nightly aerosols samples was
much higher than that in the diurnal aerosols. For both day and night samples,
inorganic phosphorus was the dominant species of DTP in aerosols, with a ratio of
71%-77%.
PMID- 29965665
TI - [Air Quality Subarea Management:A Case Study of Guangdong Province].
AB - To meet the requirements of regional air quality management (AQM), the Air
Quality Subarea Management (AQSM) system was proposed. A case study was conducted
for Guangdong Province. By using the method of air quality numerical simulation
and satellite remote sensing inversion analysis, the key factors were selected
from the meteorological simulation field, the pollutant concentration simulation
field, and the satellite image interpretation to form the index system for AQSM.
On this basis, a hierarchical cluster analysis method was used to divide
Guangdong Province into three types of AQSM:Strict Control Subarea, Continuous
Improvement Subarea, and Coordinated Development Subarea. It was shown that the
Strict Control Subarea, Continuous Improvement Subarea, and Coordinated
Development Subarea in Guangdong Province covered 16.3%, 28.0%, and 55.7%,
respectively. The Strict Control Subarea in the Pearl River Delta, Eastern
Guangdong, Western Guangdong, and Northern Guangdong accounted for 27.9%, 19.3%,
4.4%, and 12.5%, respectively, and the subarea should implement the most
stringent AQM policies to promote air quality improvement. The Continuous
Improvement Subarea in the Pearl River Delta, Eastern Guangdong, Western
Guangdong, and Northern Guangdong accounted for 34.4%, 15.8%, 7.8%, and 34.5%,
respectively, and the subarea should implement relatively strict AQM policies to
ensure sustained and stable standards. The Coordinated Development Subarea in the
Pearl River Delta, Eastern Guangdong, Western Guangdong, and Northern Guangdong
accounted for 37.7%, 64.9%, 87.8%, and 53.0%, respectively, and the subarea could
implement more liberal AQM policies to ensure relatively good air quality. In
general, the strict AQM policies in Guangdong Province should be mainly
concentrated in the Pearl River Delta region, followed by Northern Guangdong,
Eastern Guangdong, and Western Guangdong in order.
PMID- 29965666
TI - [Remote Sensing Identification of Urban Black-Odor Water Bodies Based on High
Resolution Images:A Case Study in Nanjing].
AB - The identification of urban black-odor water bodies plays an important role in
monitoring and controlling black-odor water bodies. In 2016, a ground survey was
conducted on the urban reach of Nanjing, and 55 samples from the West Shazhou
River, Tuwei River, Xuanwu Lake, and Jinchuan River were obtained. The spectral
characteristics of urban black-odor water bodies and other water bodies were
analyzed. Recognition algorithms for GF-2 data were proposed in order to analyze
the spatial distribution and environmental factors of urban black-odor water
bodies. These algorithms were single-band thresholds based on reflectance of the
green band, the difference between the blue band and green band, the ratio of the
green band and red band, and the chromaticity value. The results indicate that:1
compared with other types of water, the urban black-odor water has the smallest
spectral slope in the range of 400-500 nm and lowest reflectivity, and the peaks
and valleys are not prominent in the whole visible range; 2 based on the
verification, the accuracy of the ratio algorithm is the highest; and 3 using the
ratio algorithm to calculate the GF-2 data of November 3, 2016, a total of 11
black river sections are identified. The entire length is 40.7 km, and the area
is 0.749 km2.The black-odor water sections are distributed over a wide range but
are not continuous, and they are concentrated in the densely populated areas.
Domestic sewage, industrial waste water, and broken river channel are the main
reasons.
PMID- 29965667
TI - [Simulation of Nitrate Isotopic (delta15N and delta18O) by Coupling the Hydrology
and Transport Processes Described by the SWAT Model].
AB - To improve the reliability of methods to trace surface water pollutants in river
basins, hydrological and water quality processes in the Fuxi River Basin were
continuously monitored from 2013 to 2015, and the main pollution sources in the
watershed and delta15N as well as delta18O in the rivers were measured
simultaneously. The Soil and Water Assessment Tool (SWAT) model was used to
simulate the NH4+ and NO3- migration processes in the hydrological processes of
the land surface and rivers. On this basis, the processes of mixing,
transformation, and fractionation of delta15N and delta18O in NO3- were coupled,
and the simulation methods of delta15N and delta18O in the rivers were developed.
The results showed that delta15N and delta18O in the rivers were mainly affected
by the pollution sources in the river basin and the variation in runoff
conditions during different hydrological periods. The contribution of the mixing
process of different isotopes to the isotope abundance was 82.74%. The
contribution of isotope fractionation in the process of nitrogen conversion was
16.26%. The influence of NH4+ and NO3- concentration deviation from the SWAT
simulation on the simulation errors of delta15N and delta18O was 10.44%. The
delta18O simulation errors were 18.72% larger than those of delta15N because of
the higher variation range of delta18O in rainfall and the complexity of
delta18O. The systematic errors and deviations of the simulated delta15N and
delta18O results using the proposed method were less than 10% and 15%,
respectively. The simulation method of delta15N and delta18O in the river basin
has a clear physical meaning, which provides a useful approach for tracing
nitrogen sources in rivers.
PMID- 29965668
TI - [Estimation of and Control Strategies for Pollution Loads from Non-point Sources
in the Chenghai Watershed].
AB - The calculation of non-point source (NPS) pollutant loads of nitrogen and
phosphorus is the key step in preparing a pollution control plan. This study
modified the export coefficient model by taking into account the precipitation,
slope, distance between pollution sources and water bodies, and other relevant
factors. The NPS pollution load assessment method established in this study can
be applied to data-scarce basins and is suitable for plateau lake regions
affected by terrain and precipitation. In this study, Chenghai Lake, which
belongs to one of the nine major plateau lakes in Yunnan Province, is selected
for the case study. This study first verifies the rationality of the improved
export coefficient model based on actual observed values, and then utilizes the
improved export coefficient model to assess the loads of dissolved nitrogen (DN)
and dissolved phosphorus (DP) pollution. As indicated by the results, in 2014,
the loads of DN and DP into Chenghai Lake are 158.48 t.a-1 and 24.70 t.a-1,
respectively. The maximum contributions of DN and DP pollution load into Chenghai
Lake are from agricultural cultivated land are 46.19% and 48.16%, respectively,
in terms of land use. The results present a relatively consistent spatial
distribution of DN and DP that indicates that the south bank is a key area for
governance. Livestock and rural living are the main pollution sources influencing
the load of DN and DP into Chenghai Lake and should be prioritized for control.
If the pollution from rural living, livestock, fertilizer loss, and land use can
be effectively controlled, the load of DN and DP into Chenghai Lake will be
decreased by a maximum of 38.47% and 40.76%, respectively. The results of this
study suggest that the improved export coefficient model can be applied for study
of the NPS pollution assessment of plateau lake regions and can provide a
theoretical basis for the NPS pollution control of the Chenghai Lake basin.
PMID- 29965669
TI - [Distribution Characteristics and Health Risk Assessment of Metals in Drinking
Water Sources from the Luhun Reservoir].
AB - In order to investigate the distribution characteristics and the human health
risks of 12 metals in drinking water sources from the Luhun Reservoir, Al, As,
Cd, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, and Zn concentrations in 46 water samples
collected from the reservoir in 2016 were measured and analyzed. The health risks
caused by metals were assessed by using a human health risk assessment model. The
results showed that the maximum concentration of Al (200.27 MUg.L-1) and all
concentrations of Mo (151.42-170.69 MUg.L-1) in drinking water from the Luhun
Reservoir exceeded the Environmental Quality Standards for Surface Water (GB 3838
2002) and Standards for Drinking Water Quality (GB 5749-2006) by 4.35% and 100%,
respectively. A distinct spatial heterogeneity was found in the metal
distribution, and the region with the highest metals concentrations was located
southwest (upstream) and northeast (downstream) of the reservoir. The results of
a health risk assessment indicated that children had greater health risks than
adults. The health risks for metals through drinking were all higher than the
values caused by dermal contact. Carcinogenic risks caused by Cr and As exceeded
the maximum allowance levels (5*10-5 a-1) by 100% and 3.80%, respectively, and Cr
accounted for 85% of the total carcinogenic risks. The non-carcinogenic risks of
the metals (10-12-10-7 a-1) decreased in the order of Al > Mo > Cu > Pb > Ni > Hg
> Fe > Zn > Mn, which had levels two to seven orders of magnitude lower than the
maximum allowance levels.
PMID- 29965670
TI - [Distribution Characteristics and Health Risk Assessment of Antibiotics in the
Water Supply System in Tianjin].
AB - Six groups of 10 antibiotics in the water plants and water supply network in
Tianjin were sampled and analyzed by using solid phase extraction and high
performance liquid chromatography-mass spectrometry. The concentrations of 10
antibiotics were detected in the water treatment process units, and the
distribution, migration, and health risk assessment in the water supply networks
were studied. The results of antibiotic determination in the water plants showed
that the antibiotic concentrations were 0.96-126.43 ng.L-1, and the removal
efficiency was -46.47%-45.10% in plant A using traditional treatment processes.
The coagulation treatment process was effective for the antibiotic removal in
plant A. In plant B with an advanced treatment process, roxithromycin was not
detected, and the concentration of other antibiotics was ND-72.27 ng.L-1. The
removal efficiency of the antibiotics was 40.25%-70.33% in plant B, which was
remarkably higher than that in plant A. The results indicated the process of UV
combined with chlorine disinfection played a major role in removing antibiotics
in plant B. In addition, the antibiotic distribution in the water pipes indicated
that the detection rate of roxithromycin was 75.0% and that for other antibiotics
was 100.0%. The concentration of 10 antibiotics was ND-348.99 ng.L-1 and
decreased gradually with the increase of the transmission distance, which
followed the first order reaction kinetics model. Based on the Monte Carlo
method, the carcinogenic and non-carcinogenic health risks of antibiotics in
drinking water were assessed. The results displayed that both were at an
acceptable level of risk.
PMID- 29965671
TI - [Organic Distribution Characteristics and Influence on Drinking Water Quality in
the Typical Water Sources for Towns in the Southwest Hilly Area of China].
AB - This study analyzed the organic distribution characteristics of original and
treated water and their impacts on drinking water quality using a conventional
water treatment process in the typical water supply sources for towns in the
southwest hilly area of China. The results showed that the water supply source in
this area is micro-polluted water. Dissolved organics of low molecular weight
accounted for the great majority of the organics, with the proportion ranging
from 50% to 80%. There were 53 kinds and 14 classes of organics, including
alkanes, esters, phenolic compounds, and benzenes, with the proportion from 80%
to 90%. The amounts of organic acid, alkene, alcohols, and aldehyde were small,
while the amounts of dichloromethane, phenol, and dibutyl-phthalate were
relatively high. Herbicides, food additives, and antibiotics were detected, such
as terbuthylazine, 2,6-di-tert-butyl-p-cresol, and nalidixic acid. The
conventional water treatment process could efficiently remove the compounds with
molecular weights higher than 10*103 and organic acid; however, it was limited
greatly in its removal of alkanes, esters, phenolic compounds, and benzenes.
PMID- 29965672
TI - [Health Risk Evaluation of Organochlorine and Organophosphorous Pesticides in
Groundwater in Beijing].
AB - Pollution from organochlorine (OCP) and organophosphorus (OPP) pesticides in
groundwater is a key issue for water resource protection. Sixteen kinds of OCP
and six kinds of OPP pesticides were detected in 18 groundwater samples
determined by GC-MS. Results showed that seven kinds of OPCs and two kinds of
OPPs were found in the groundwater in Beijing. Among the OCPs, there were mainly
hexachlorobenzene (HCB), hemochromatosis (HCH), and
dichlorodiphenyltrichloroethane (DDT), with maximum values of, respectively,
82.4, 193, and 158 ng.L-1. Among the OPPs, there were o, o-dimethyl-o-2,2
dichlorovinylphosphate and o,o-dimethyl methylcarbamoylmethyl phosphorodithioate,
with maximum values of 7.1 ng.L-1 and 17.7 ng.L-1, respectively. The OCPs and
OPPs were found in the sewage irrigation areas. The results of a probabilistic
risk assessment showed that the non-carcinogenic and carcinogenic risks of OCPs
and OPPs within the drinking water in Beijing had been controlled, that risks
from OCPs were higher, and that women were more sensitive to the toxicity of the
pesticides. The monitoring of HCH and DDT in the groundwater should be
implemented.
PMID- 29965673
TI - [Pollution Status and Risks of Dioxin-like Polychlorinated Biphenyls in the Soil
of the Yellow River].
AB - The concentration levels, toxic equivalency (TEQ) concentrations, and
carcinogenic and non-carcinogenic risks of dioxin-like polychlorinated biphenyls
in shore soil from the 40 national key monitoring sections along the entire
Yellow River were comprehensively studied. The results showed that the
concentrations of SigmaDL-PCBs in the soil were between 0.37-7.17 ng.g-1 (dry
weight), and the mean value was 0.38 ng.g-1 (dry weight). The TEQ concentrations
of DL-PCBs in the soil were between 0.00-30.31 pg.g-1 (dry weight), and the mean
value is 13.63 pg.g-1 (dry weight), posing no significant risk to the ecological
environment and human health. The carcinogenic and non-carcinogenic risks of DL
PCBs in this study did not exceed the limits set by the USEPA, and there were no
obvious health risks. The residents in the middle reaches of the Yellow River
were more vulnerable to DL-PCBs.
PMID- 29965674
TI - [Effects of Flooding and Drying on the Transformation of Soil Inorganic
Phosphorus in the Water-Level-Fluctuating Zone of the Three Gorges Reservoir,
China].
AB - The implementation of the Three Gorges Project formed a water-level-fluctuating
zone, and flooding and drying affects the soil properties and water quality of
the Water-Level-Fluctuating Zone. The laboratory simulation or field sampling
were conducted; however, the results cannot reflect the real conditions in
practice. The effects of flooding and drying on the physical and chemical
properties of soil and the transformation characteristics of inorganic phosphorus
were studied in order to provide a theoretical reference for soil phosphorus loss
and water eutrophication in water-level-fluctuating zone of the Three Gorges
Reservoir. To investigate the conversion of soil phosphorus, plastic pots with
soil were suspended at different depths (0, 2, 5, and 15 m) and submerged for 30,
60, and 180 d, and exposed for 180 d. The effects of submerged depth and time on
the soil physical and chemical properties and inorganic phosphorus forms were
studied. The results showed that soil pH, organic matter, total phosphorus, and
available phosphorus decreased and then increased subsequently during the
flooding period. After exposure for 180 d, soil pH, organic matter, and total
phosphorus content decreased, while available phosphorus content increased. After
flooding, the ratio of various forms of inorganic phosphorus to total phosphorus
was Fe-P > Al-P > Ca8-P > Ca2-P. The content of Ca2-P and Ca8-P decreased at 0 m
and 2 m and decreased at 5 m and 15 m and then increased with increased flooding
time. After exposure for 180 days, the content of inorganic phosphorus increased
significantly, and the content of inorganic phosphorus decreased as flooding
depth increased. Al-P content increased with the flooding time, but there was no
obvious change with flooding depth. The content of Fe-P did not change with the
time and the depth of flooding.
PMID- 29965675
TI - [Effect of Phosphate on the Ammonium Removal Performance of Iron-Manganese Co
oxide Film in Surface Water Treatment].
AB - The effect of phosphate on the ammonium removal performance of iron-manganese co
oxide film coated quartz sands in surface water treatment was investigated in a
pilot-scale filtration system. The experimental results showed that the removal
efficiency of ammonium decreased with reaction time without phosphate, while it
stabilized at a level over 95.3% with phosphate dosing of 5-15 MUg.L-1 at a
temperature between 17.2-21.9C. The effluent ammonium concentration of the filter
columns exceeded the permitted limits for drinking water, when the water
temperature was below 10.5C. Fortunately, it can meet the water standards by
increasing the amount of dosed phosphate to 30 MUg.L-1 or increasing the height
of the filter layer. However, the ammonium concentration in the effluent of the
filter when only increasing the height of the filter layer exceeded the water
standards after running for several days. The maximum safe concentration of
ammonium in the influent of the filters with 120 cm and 80 cm height active
filter beds were 2.34 and 1.95 mg.L-1 with the condition of 30 MUg.L-1 phosphate,
respectively. Microorganism inactivation experiments indicated that the ammonium
removal capability of the activated oxide film included catalytic oxidation and
biological nitrification simultaneously. The total activity and catalytic
oxidation activity of the activated oxide film were 1.36 times and 1.79 times
higher than those without phosphate, respectively, which suggested that phosphate
can facilitate the catalytic oxidation activity of the activated oxide film.
PMID- 29965676
TI - [Enhanced Photoelectrocatalytic Oxidation of Cu(CN)32- and Synchronous Cathodic
Deposition of Cu by Peroxydisulfate].
AB - Oxidation of Cu-cyanides by a photoelectrocatalytic method was enhanced by adding
peroxydisulfate (PS). In the photoelectrocatalytic system (PEC), graphitic carbon
nitride (g-C3N4) thin films prepared by a liquid-based reaction and graphitic
carbon felt (GCF) were used as the photoanode and cathode, respectively. First,
various processes, including PEC, PS oxidation, and PEC with PS addition
(PEC/PS), were compared for Cu-cyanide removal. The addition of PS improved
greatly the photoelectrocatalytic efficiency for the oxidation of CN- and the
recovery of Cu on the cathode. The effect of the amount of K2S2O8 was
investigated in detail. The removal efficiency of CN- and Cu recovery can reach
up to 86.23% and 82.11%, respectively, with 1 mmol.L-1 K2S2O8 at 1.0 V bias
potential. Combined with the SEM, EDS, and XPS analysis of the electrode surface,
it was concluded that the free Cu+ was oxidized and existed in the precipitation
and photoanode in the form of CuO. Conversely, the liberated Cu+/Cu2+ ions were
electrochemically reduced to elemental Cu on the surface of the graphitic carbon
felt cathode. As a result, metal Cu was recovered from the wastewater of the
copper cyanide complexes. Electron spin resonance and radical quenching
experiment analysis showed that the oxidation of CN- is assigned to sulfate
radical oxidation and non-radical oxidation processes.
PMID- 29965677
TI - [Using HKUST-1 as a Template for Copper Oxides Preparation to Activate
Peroxymonosulfate for RhB Degradation].
AB - Using Cu-MOF (HKUST-1) as a template, copper oxide was prepared by heat treatment
under different temperatures in this study. The effect of treatment temperature
on the composition and morphology of the products were studied. The catalytic
abilities of the copper oxide products were tested through a series of
experiments of activating peroxymonosulfate (PMS) to degrade RhB under different
conditions. The results of XRD, SEM, and XPS show that the product is gradually
transformed from a Cu2O/CuO mixture into pure CuO with the increase of heat
treatment temperature. The original octahedron structure of HKUST-1 was
collapsed. Under neutral pH conditions, when the dosage of PMS and CuO-650 was
1.00 mmol.L-1 and 0.20 g.L-1, respectively, the total degradation of RhB
(concentration of 0.10 mmol.L-1) could be completed within 90 min. In addition,
CuO-650 also has many advantages, such as it can be applied within a wide range
of pH values. In addition, the copper ion dissolution rate was low (1.309 mg.L-1
at pH=3 and 0.987 mg.L-1 at pH=7), and it has great recyclability and stability.
These characteristics further proved that CuO-650 can be used as a promising
catalyst for PMS activation.
PMID- 29965678
TI - [Evaluation of Performance of an Aminated Rosin-based Resin for Adsorption of
Norfloxacin from Aqueous Solutions].
AB - An aminated rosin-based resin (ARBR) was synthesized as a novel environmentally
friendly adsorbent for removal of Norfloxacin (NOR) from aqueous solutions. Its
features were characterized by scanning electron microscopy (SEM), Fourier
transform infrared spectroscopy (FTIR), and surface area measurements (BET). The
effects of resin dosage, pH, and ionic strength on the ARBR adsorption properties
of NOR were investigated by batch experiments. Results showed that the NOR
adsorption amounts increased with pH in the range from 2.0 to 6.0, but decreased
at higher pH (8-10). The adsorption process of NOR followed a pseudo-second rate
model and could be fitted to the Langmuir isotherm, with calculated maximum
monolayer adsorption capacity of 30.29 mg.g-1 at pH 6.0 and 20C. Thermodynamic
calculations showed that the adsorption of NOR was a spontaneous and endothermic
process and could be attributed to a combination of electrostatic interactions
and hydrogen bonding. Furthermore, the adsorbed NOR on ARBR could be efficiently
desorbed by 0.1 mol.L-1 HCl to regenerate the resin. After five adsorption
desorption recycles, ARBR had a stable adsorption performance and could be
recycled. The adsorption performance is better than that of various commercial
resins, and these research results contribute to the development of applications
of rosin derivatives and their utilization in the environmental control of micro
pollutants.
PMID- 29965679
TI - [Arsenic(V) Removal by Granular Adsorbents Made from Backwashing Residuals from
Biofilters for Iron and Manganese Removal].
AB - Granular adsorbents for arsenic removal (GA) made from the backwashing residuals
from iron and manganese removal biofilters for groundwater were characterized and
examined as an arsenate sorbent. The GA were characterized by SEM-EDS microscopy,
X-ray diffraction (XRD), and BET surface area measurement. The results showed
that the GA had rough surfaces, developed pores, and were mainly amorphous, with
small fractions of crystalline quartz and hematite. The surface area of the GA,
which consists of many mesopores, was 43.8 m2.g-1. The kinetic studies revealed
that arsenate adsorption on the GA was described by a pseudo-second-order kinetic
equation, and the Freundlich isotherm equation fit the arsenate adsorption well
(R2=0.994). The maximum adsorption capacity calculated by the Langmuir isotherm
equation for As(V) was 5.05 mg.g-1. Further studies showed that the GA operated
well for As(V) removal over a broad range in pH from 1.1 to 9.5. The coexistence
of HCO3- and SO42- had no great influence on arsenic adsorption, while the H2PO4-
and SiO32- showed negative effects. The GA can be regenerated well, and 82% of
the original adsorption capacity was maintained after three regeneration cycles.
PMID- 29965680
TI - [Arsenic Adsorption and Its Species on Ferrihydrite and Ferrihydrite Colloid].
AB - Batch experiments were conducted to investigate the adsorption kinetics and
adsorption isotherms of As(III) and As(V) on ferrihydrite and its colloid. A
sequential extraction technique and As speciation extraction were used to assess
the chemically bound fractions of As and As species in solids, respectively. The
kinetic and isotherm data showed that the adsorption was multilevel and readily
occurred. The adsorption of As(III) and As(V) on the ferrihydrite colloid was
194.8 g.kg-1 and 107.3 g.kg-1, respectively, which was higher than that on
ferrihydrite (155.2 g.kg-1 and 104.4 g.kg-1). The specifically adsorbed As,
amorphous oxide bound As, and crystalline oxide bound As were the major fractions
of adsorbed As on ferrihydrite and its colloid. The residual As was absorbed on
the ferrihydrite surface instead of on the ferrihydrite colloid. Therefore, As
adsorption on ferrihydrite was much stronger than that on ferrihydrite colloid.
The ferrihydrite and ferrihydrite colloid could not reduce As(V) to As(III).
PMID- 29965681
TI - [Comparison of Amphoteric-Cationic and Amphoteric-Anionic Modified Magnetic
Bentonites:Characterization and Sorption Capacity of Phenol].
AB - Magnetic bentonite is modified by an amphoteric surfactant (dodecyl dimethyl
betaine, BS-12), then modified by a cationic surfactant (Cetyl Trimethyl Ammonium
Bromide, CTMAB) and anionic surfactant (Sodium lauryl sulfonate, SDS). Amphoteric
cationic modified magnetic bentonite (BS-CT-MBT) and amphoteric-anionic modified
magnetic bentonite (BS-SDS-MBT) are obtained. Structural identification of the
samples were characterized by scanning electron microscopy (SEM), X-ray
diffraction (XRD), thermogravimetric analyses (TG), Fourier transform infrared
spectra (FTIR), and vibrating sample magnetometer (VSM). The carbon-nitrogen
content, specific surface area, and pore volume were also evaluated. Batch
isotherm studies were conducted to evaluate the sorption of phenol. The results
show that BS-CT-MBT and BS-SDS-MBT can be separated by magnetic separation. The
carbon content-nitrogen content and content of surfactants of the BS-CT-MBT
increase, while surface area and pore volume decrease compared to those of BS
MBT. Compared with BS-MBT, the carbon-nitrogen content, content of surfactants,
and pore volume of BS-SDS-MBT are decreasing and surface area is increasing. The
desorption rate of the surfactants is less than 9% at pH 6.0 and in 0.1 mol.L-1
NaCl solution. The Henry equation is the optimal description for the phenol
sorption isotherms, implying a partitioning sorption process. The amount of
phenol sorption follows the order:BS-CT-MBT > BS-MBT > BS-SDS-MBT > BT > MBT,
which significantly correlates with the variation of the content of surfactant.
Amphoteric magnetic bentonites modified by CTMAB have better absorption
performance for phenol than those modified by SDS.
PMID- 29965682
TI - [Pollution Characteristics of Parabens in Typical Sewage Wastewater].
AB - Parabens are widely used in foodstuffs, cosmetics, and pharmaceuticals as
preservatives, fungicides, and bactericides. Recent studies showed that these
compounds could be detected in surface water and are a potential hazard to the
aquatic ecological environment. In this study, 24-hour influent samples were
collected from a typical sewage wastewater treatment plant in Harbin in autumn
and winter in 2016. The concentrations of six parabens and four normal water
quality parameters were analyzed. The results indicated that parabens were
frequently detected in the influent, and MeP, EtP, and PrP were the predominant
compounds. Significant correlations were found between TOC, TDS, pH, and the
concentration of parabens. The concentration of parabens in the influent of the
sewage wastewater treatment plant have obvious daily variations rather than
seasonal variations. The results provide an important theoretical basis for
further research and pollution control of parabens in sewage wastewater treatment
system.
PMID- 29965683
TI - [Influence of Hydraulic Retention Time on the Treatment of Polluted River Water
by an Activated Carbon Rotating Biological Contactor].
AB - The study combined activated carbon with a rotating biological contactor. The
activated carbon adsorption experiments were conducted and the biofilm was formed
by using the river water directly. The effects of different hydraulic retention
times on the removal of NH4+-N, TP, and permanganate index and on the biofilm
properties were investigated at the optimum rotational speed of the disc.
Experimental results are as follows. The Freundlich isotherm showed that
activated carbon had better adsorption properties for NH4+-N, TP, and
permanganate index in water.When the disk speed was 3 r.min-1, the removal
efficiency was the best, and the removal rates of NH4+-N, TP and permanganate
index were the best at 86.05%, 81.28%, and 77.09%, respectively. In addition,
there was a significant linear correlation between the hydraulic retention time
and the removal of NH4+-N and TP (R2>0.9), respectively. The removal rates of
NH4+-N and TP at different hydraulic retention times were significantly different
(P<0.05), but the permanganate index was not (P>0.05).Hydraulic retention time
had effects on the biofilm activity, protein and polysaccharide contents,and the
three-dimensional fluorescence peaks of S-EPS, LB-EPS, and TB-EPS of the biofilm.
PMID- 29965684
TI - [Removal and Influence of Ciprofloxacin in a Membrane Bioreactor].
AB - A membrane bioreactor (MBR) was used to treat ciprofloxacin (CIP)-contaminated
artificial wastewater. The pollutant removal performance and the microbial
community structure of the MBR were studied at three different CIP dosages (0
mg.L-1, 5 mg.L-1, and 10 mg.L-1). The results showed that the sludge
concentration in the reactor decreased and then levelled off as the dosage of CIP
was increased from 0 mg.L-1 to 5 mg.L-1 and further to 10 mg.L-1. The mean
removal of TOC and COD decreased from 98.40% and 97.80% to 84.20% and 94.10%,
respectively, indicating that the CIP negatively influenced the organic removal
but the effect was minor. In contrast, the ammonium removal was greatly
influenced by the dosage of CIP. When the CIP dosage increased from 0 mg.L-1 to 5
mg.L-1 and further to 10 mg.L-1, the ammonium removal efficiency decreased from
96.91% to 84.14% and then to 77.80%, and the activity of Nitrosomonas,
Alcaligenes, Nitrospira, and Nitrobacter were greatly inhibited. The CIP removal
initially increased and then decreased. The mass balance revealed that the
removal of CIP in the MBR was principally attributed to biodegradation and sludge
adsorption, which accounted for 30.13% and 0.25%, respectively, at a CIP dosage
of 5 mg.L-1 and 7.55% and 1.81% at a CIP dosage of 10 mg.L-1.
PMID- 29965685
TI - [Operation of the AAO Process Under Low Dissolved Oxygen Conditions and Its
Simulation].
AB - The anaerobic-anoxic-oxic (AAO) process was used to investigate the variation of
the parameters of water quality when the dissolved oxygen (DO) in the aerobic
tank was controlled at a low concentration. The results indicated the system
still had good phosphorus and nitrogen removal efficiencies when the DO
concentration in the aerobic tank was decreased from 2.00 mg.L-1 to 1.00 mg.L-1
and 0.50 mg.L-1, and the effluent indexes could meet the first class A standard
for the "discharge standard of pollutants for municipal wastewater treatment
plant" (GB18918-2002) of China. The activated sludge model of the AAO process was
developed by BioWin 4.1 software. The sensitivities of the model parameters were
analyzed, and the model parameters, such as amount of polyhydroxyalkanoate (PHA)
stored per unit of acetate or the propionate sequestered by phosphorus
accumulating bacteria (YP/PHA,seq), the amount of phosphorus stored per unit of
PHA oxidized in aerobic conditions by phosphorus accumulating bacteria
(YP/PHA,aerobic), the maximum specific growth rate of ammonia oxidizing bacteria
(MUmax,A), and the maximum specific growth rate of nitrite oxidizing bacteria
(MUmax,N), were calibrated and validated by the dynamic simulation. In addition,
the energy consumption of the aeration was simulated and evaluated. The results
showed that when the DO concentration in the aerobic tank was decreased from 2.00
mg.L-1 to 1.00 mg.L-1 and 0.50 mg.L-1, the air flow could be reduced by 23.8% and
38.1%, and the oxygen transfer efficiency could be increased by 7.2% and 11.7%,
respectively.
PMID- 29965686
TI - [Inhibitory Effects of Phosphate and Recovery on a Nitrification System].
AB - The effect of phosphate concentration on nitrification was studied by using a
stabilization nitrosation system, which was started up in a continuous flow
reactor by inoculating sludge from a municipal wastewater treatment plant. The
results showed that the nitrification system was started successfully after
operating for 14 days. The conversion rate of ammonia nitrogen reached 92.2%, the
nitrite accumulation rate was 73.66%, and the nitrite generation rate was 14.42
g.(m3.d)-1. There was no effect of phosphate concentration on the nitrosation
system between 10 and 30 mg.L-1; and the conversion rate of ammonia nitrogen was
decreased with the continuous increase in phosphate concentration. When the
concentration of phosphate was 80 mg.L-1, with an ammonia conversion rate 13.6%,
accumulation rate of nitrite of 18.19%, and nitrite generation rate of 0.54
g.(m3.d)-1, the reaction was severely inhibited. After reducing the influent
phosphate concentration to 0, with the ammonia nitrogen conversion rate at more
than 80%, nitrite accumulation rate improved to 86.96%, and the nitrite
generation rate being 15.63 g.(m3.d)-1, the system recovered after operating for
14 days.
PMID- 29965687
TI - [Effect of Carbon Source on Lab-scale SAD Process in a Wastewater Treatment
Plant].
AB - Lab-scale anaerobic ammonia oxidation and denitrification (SAD) processes were
operated simultaneously in a municipal waste water treatment plant (WWTP). Sewage
treated by the A/O and nitrification process was used as the substance to start
up an anaerobic ammonia oxidation filter reactor. Adding glucose and sodium
propionate to influent was used as the substance to start up the SAD filter
reactor after the successful start-up of the ANAMMOX reactor. The SAD process
performed well with an average total nitrogen concentration in the effluent of
6.41 mg.L-1 when 30 mg.L-1 glucose was added to the effluent sewage at ambient
temperature. Compared with the ANAMMOX process, the total nitrogen concentration
in the effluent from the SAD process decreased 42%. The stability of the SAD
process was destroyed and the SAD process turned into a denitrification process
when 30 mg.L-1 glucose was added in the influent sewage in a low temperature
environment. In normal and low temperature environments, the SAD process
functioned well, and the average total nitrogen concentration of the effluent was
6.54 mg.L-1 when 30 mg.L-1 sodium propionate was added in the influent sewage.
Compared with glucose, sodium propionate had little influence on the SAD process.
PMID- 29965689
TI - [Combined Process of DNBF-O3-GAC for Nitrogen and Phosphorus and Metabolite
Advanced Removal].
AB - To improve the quality of the tailings water from a wastewater treatment plant
(WWTP), a denitrification biofilter (DNBF) with a composite filler composed of a
new slow-release organic-carbon source (SOC-F), sponge iron, and activated carbon
was tested. Studies were conducted in the combined process of DNBF-O3-GAC to
explore the efficiency of the advanced removal of nitrogen, phosphorus, and
microbial metabolite by using synthetic effluent made from running water and
chemicals. Corresponding comparative studies were conducted by using the
secondary effluent from the WWTP. The microbial population structure in the
biofilm of the denitrification biofilter was analyzed by adopting MiSeq high
throughput sequencing technologies. The results indicated that the combination
process achieved high efficiency removal of nitrogen, phosphorus, and microbial
metabolite. The average removal rate of NO3--N in the simulated and actual water
period reached 88.87% and 79.99%, respectively; the average removal rate of TP
reached 87.67% and 65.51%, respectively; and the average removal rate of UV254
reached 45.51% and 49.23%, respectively. Each processing unit had different
functions. The changes in NO3--N, TN, TP, and TFe mainly occurred in the
denitrification biofilter, and the removal of UV254 and the change in the three
dimensional fluorescence intensity mainly occurred in the ozone-activated carbon
reactor. The cluster analysis at the genus level indicated that the
denitrification system had sulfur autotrophic denitrifying bacteria and
heterotrophic denitrifying bacteria. Sulfur autotrophic denitrification increased
obviously in the actual water period when relatively lack of carbon sources, and
the proportion of Thiobacillus increased from 7.44% to 29.62%. The complementary
effect of sulfur autotrophic denitrification and heterotrophic denitrification
had extended the use of the new slow-release carbon source.
PMID- 29965688
TI - [Effect of Volume Loading Rate (VLR) on Denitrifying Phosphorus Removal by the
ABR-MBR Process].
AB - The effect of volume loading rate (VLR) on denitrifying phosphorus removal was
investigated in a continuous-flow ABR-MBR combined process treating domestic
wastewater to arrive at optimum process parameters. In the experiment, the VLR of
the ABR was set at 0.76, 1.01, 1.51, and 2.27 kg.(m3.d)-1. The removal of carbon,
nitrogen, and phosphorus in the system and the effect of the VLR in the MBR on
nitrification performance were observed for each VLR of the ABR. The results
showed that under the condition when the VLR of the ABR was 1.51 kg.(m3.d)-1, the
amount of COD removal in the A2 chamber was the largest, and shortcut
nitrification was achieved in the MBR when the VLR of the MBR was 1.51 kg.(m3.d)
1. Meanwhile, the removal efficiency of NH4+-N and TN reached more than 90% and
72%, respectively, the anaerobic P-release and anoxic P-uptake were 7.41 mg.L
1and 15.42 mg.L-1, respectively, and the concentration of PO43--P in effluent was
lower than 0.5 mg.L-1, which indicated that the shortcut nitrification was more
conducive to strengthening the performance of denitrifying phosphorus removal in
the ABR-MBR system.
PMID- 29965690
TI - [Influence of Operating Modes for the Alternating Anoxic/Oxic Process on
Biological Nitrogen Removal and Extracellular Polymeric Substances of Activated
Sludge].
AB - Nitrogen removal, extracellular polymeric substances (EPS), and the chemical
composition (protein (PN), polysaccharide (PS), and DNA) by the aerobic/anoxic
(O/A) and the anoxic/aerobic (A/O) modes were studied in a sequencing batch
reactor (SBR) fed with domestic wastewater. The results showed that the removal
rates of NH4+-N were 97.5% and 98.0% in the two operating modes, respectively,
and a removal efficiency of NH4+-N with high efficiency and stability was
obtained. The nitrification rate was positively correlated with the nitrogen
loading ratio. The influence of operating modes for the alternating anoxic/oxic
mode on extracellular polymeric substances of activated sludge was evaluated. The
EPS constituent in the A/O mode was slightly higher than the O/A mode. The
operating mode had no effect on the contents of PN, PS, and DNA in tightly bound
EPS (TB-EPS) and TB-EPS. However, PN and PS in loosely bound EPS (LB-EPS) and LB
EPS in the A/O mode were 1.38 to 1.56 times those of the O/A mode. In the two
operating modes, PSs were the main constituents in the TB-EPS and EPS, while PNs
were the main constituents in LB-EPS. The EPS content had a good linear
correlation with the sludge settling performance.
PMID- 29965691
TI - [Effects of Nanoscale Zero-valent Iron (nZVI) on Denitrifying Performance of an
Upflow Granular Sludge Bed Reactor].
AB - In order to examine the effects of nanoscale zero-valent iron (nZVI) on the
performance of denitrifying granular sludge (DGS) in a continuous flow model, the
variations of nitrogen removal efficiency in the reactor, sludge morphology, and
denitrifying characteristics at different influent nZVI concentrations were
investigated in an upflow sludge bed (USB). The results showed that nZVI
concentrations lower than 5 mg.L-1 did not influence the nitrogen removal
performance of the reactor significantly, and the activity of DGS was improved
slightly. When the influent nZVI concentration was in the range of 5 to 10 mg.L
1, the DGS could adapt to the biological inhibition of nZVI partially, with the
increase of sludge concentration and grain size. However, the higher total iron
contents in the sludge resulted in the lower denitrifying activity of the DGS.
The removal efficiencies of COD and NO3--N in the reactor decreased to 23.3% and
20.3%, respectively, at the influent nZVI concentration of 30 mg.L-1. Moreover,
the DGS was a dark color and of a smaller grain size because of the adsorption of
a large amount of nZVI, while the microbe density, such as that of the bacillus
species, on the granule surface decreased significantly. In the recovery phase,
the nitrogen removal performance of the reactor could almost reach its initial
level at nZVI=0 mg.L-1 during an operation of 20 days due to the fast growth of
heterotrophic microbes on the surface of the DGS.
PMID- 29965692
TI - [Influence on Desulfurization Efficiency and Interactions of Fe/S and pH During
H2S in situ Depression of High Solid Anaerobic Digestion].
AB - To evaluate the influence of Fe/S ratio and pH on sulfide removal efficiency and
interactions between Fe/S and pH, anaerobic hydrogen sulfide in situ depression
tests and digested sludge liquor sulfide removal tests were carried out by using
dewatering sludge from a wastewater treatment plant (WWTP). Results showed that
the concentration of hydrogen sulfide in biogas from the thermal pretreatment
following anaerobic digestion process could be reduced from 170.4*10-6 to
14.09*10-6 at Fe/S=7.75, which means the biogas desulfurization treatment is not
required. Under the condition of pH 7.00-7.50 and Fe/S 1-11, pH is the main
influencing factor for sulfide removal. Improving the pH of anaerobic digestion
is beneficial in reducing the dosage of Fe(III). An Fe/S ratio of 7.0 is the
minimum to meet the biogas hydrogen sulfide emission standards during high solid
sludge anaerobic digestion. The concentration of hydrogen sulfide was not up to
standards if pH was below 7.30.
PMID- 29965693
TI - [Analysis of Storage Sludge Composition Characteristics and Evolutionary
Regularity in the Hunhe River Basin].
AB - With the acceleration of urbanization, the accumulation of storage sludge in the
Hunhe River Basin has increased year by year, creating a potential and long-term
threat to the environment. In order to realize the resource-saving and harmless
treatment of storage sludge, the composition of storage sludge and the evolvement
rule were analyzed and researched. The basic physicochemical properties (water
content, pH, volatile organic compounds (VS), and total alkalinity), nutrient
index (TC, TN, C/N, TK, and TP), microbial composition, and heavy metal contents
and fraction were analyzed. The results showed the VS and various nutrient
element contents decreased with the prolongation of storage time, and changes in
water content were not obvious, which was independent of the storage time and
only relevant to natural conditions. The pH was maintained at around 7, and the
bacteria predominated in microorganisms, accounting for about 90%. The content of
anaerobic microorganisms increased. The contents and fractions of Cu, Zn, Cr, Ni,
Pb, Cd, As, and Hg did not change significantly, but the content of Cu was higher
than the Chinese standard for agricultural utilization (GB 4284-1984). Therefore,
there is a larger risk of storage sludge for agricultural use. Therefore, the
analysis of the composition and evolution of storage sludge in the Hunhe River
Basin is of great significance for further resource treatment of sludge.
PMID- 29965694
TI - [Enhancement of Anaerobic Methane Production by Removal of Organic-bonding Metals
from Sewage Sludge].
AB - To improve anaerobic digestion biogas yield, the removal of organic-bonding
metals by EDTA pretreatment was investigated to strengthen the anaerobic biogas
effect. The results showed that after EDTA pretreatment (experimental group), the
organic-bonding metals were reduced from (5.09+/-0.57)% to (1.37+/-0.20)%
(calculated with TS) and dissolved organic matter increased significantly (SCOD
improved 627%), suggesting that this method could remove a large amount of
organic-bonding metals and enhance the dissolution of organic sludge. According
to the results for the apparent activation energy (AAE) of sludge organic matter
dissolution, the AAE of the experiment group was 36% lower than the control
group, showing that pretreatment could effectively reduce the reaction energy
barrier for organic matter dissolution. In a test of anaerobic acid production
lasting 16 days, the VFAs of the experiment group were higher than the control
group, with the largest upgrade of 42%. In the anaerobic methane production test
(BMP) that lasted for 22 days, compared with control group, the accumulated
biogas production of the experiment group increased by 48%. Through further
research on the dynamics of methane production, the rate-limiting step in the
experiment group was methanogenesis, while that of the control group was
hydrolysis, indicating that removal of organic-bonding metals by EDTA
pretreatment could effectively accelerate the hydrolysis rate.
PMID- 29965695
TI - [Comparison of Different Leaching Methods for Heavy Metals in Sludge Fly Ash and
Comprehensive Toxicity Evaluation].
AB - Fly ash from sludge incineration was separated into five different sizes (<1 MUm,
1-2.5 MUm, 2.5-10 MUm, 10-50 MUm, and > 50 MUm) by high-precision air
classification equipment. The leaching of heavy metals was contrastively studied
using the HJT 299-2007-sulfuric acid/nitric acid method, HJ 557-2009-Horizontal
Oscillation Method, toxicity characteristic leaching procedure (TCLP), and
European standard protocol (EN 12457-3) for the different size fractions of the
fly ash. Based on the leaching results, an evaluation method for the
comprehensive toxicity of heavy metal leaching was established. The results show
that the content of heavy metals and the amount of leaching from the fly ash
decrease with the increase in fly ash particle size. The leaching of the heavy
metals Zn and Cu in the < 1 MUm particle size range of TCLP leaching method was
the highest, at 107.34 mg.kg-1 and 318 mg.kg-1, respectively. The TCLP and
sulfuric acid/nitric acid methods of heavy metal leaching were more effective
than the EU (EN 12457-3) and horizontal oscillation methods. According to the
value of OPTI, the OPTI value of < 10 MUm fly ash was much larger than that of
fly ash that was > 10 MUm. This indicated that the fly ash of particle size < 10
MUm was more toxic and more harmful.
PMID- 29965696
TI - [Diurnal Variations of CH4 and N2O Fluxes from the Drained Aquaculture Pond in
the Minjiang River Estuary During Early Winter].
AB - Annual drainage is a typical management activity practiced by operators as a way
to export aquaculture effluent, accelerate aerobic decomposition of bottom soils,
and avoid eutrophication during the non-culture period after harvest. Drainage
activities can cause large changes in hydrology, nutrient cycling, sediment
physicochemical properties, and even broad ecosystem functions. In order to
understand the effects of drainage on the diurnal variation characteristics and
magnitude of greenhouse gas (CH4 and N2O) fluxes from the aquaculture ponds of
the estuaries, a 24-hour continuous monitoring was conducted from one undrained
pond (UDP) and one drained pond (DP) during early winter in the Minjiang River
estuary on the southeast coast of China. Over the entire study period, the fluxes
of CH4 from the UDP and DP ranged from 0.04 to 0.10 mg.(m2.h)-1 and 14.04 to
33.72 mg.(m2.h)-1, respectively, with means of (0.07+/-0.01) mg.(m2.h)-1 and
(24.74+/-2.33) mg.(m2.h)-1. The CH4 flux was lower during the day and higher at
night with a net flux as the sources of the CH4. The fluxes of N2O from the UDP
ranged from -0.027 to 0.011 mg.(m2.h)-1, and the average fluxes of (0.002+/
0.004) mg.(m2.h)-1 showed "weak absorption by day and emission at night." The N2O
fluxes from the DP were emitted all day (ranging from 0.59 to 1.76 mg.(m2.h)-1)
with the average fluxes of N2O (1.07+/-0.15) mg.(m2.h)-1 indicating higher fluxes
at night and lower fluxes during the day. Our research demonstrated that drainage
would significantly enhance CH4 and N2O release from the aquaculture ponds. The
study also preliminarily confirms that the undrained pond converted to a drained
pond considerably alter the diurnal variation characteristics of the CH4 and N2O
emissions during early winter. Clearly, future measurements in situ at high
frequency over a long time and at different spatial scales would be worth
researching from drained aquaculture ponds.
PMID- 29965697
TI - [Effects of Three Soil Amendments on Greenhouse Gas Emissions From Corn Fields in
the Hetao Irrigation District].
AB - In order to study the effects of soil amendments on greenhouse gas emissions,
five different fertilization treatments (no fertilization, conventional
fertilization, conventional fertilization+bentonite, conventional
fertilization+biochar, and conventional fertilization+potassium polyacrylate,
labeled as NF, CK, B, C, and PAM) were applied on corn fields in the Hetao
irrigation district during the maize growing seasons of 2015 and 2016, and the
samples were analyzed by static chamber-gas chromatography. The results showed
that N2O had a bimodal emission pattern in the Hetao Irrigation Area, and the N2O
emission peak appeared five to seven days after topdressing and irrigating
(d.p.ti). The CH4 emission had no apparent pattern. While the CH4 emission peak
appeared with a few treatments after 6 d.p.ti, the rest of the period indicated
the CH4 absorption in the soil. CO2 had a unimodal emission pattern, and the CO2
emission peak appeared during the jointing stage of maize growth. In addition,
the correlation analysis indicated that an increase in soil temperature could
significantly increase the N2O and CO2 emission rates. Moreover, compared with
the CK treatment, the B and PAM treatments could significantly decrease the
cumulative emission of N2O (P<0.05), with a decline of 38.59% and 45.35%,
respectively. The B and C treatments could significantly enhance the soil uptake
of CH4 (P<0.05), and the cumulative absorption of CH4 increased 144.44% and
172.22%, respectively. The B and C treatment results were significantly different
from the CK treatment based on the cumulative emission of CO2 (P<0.05), with a
decrease of 25.40% and 22.21%, respectively. In general, compared with the CK
treatment, the comprehensive warming potential of the B, C, and PAM treatments
declined by 27.77%, 19.61%, and 12.16%, respectively. The greenhouse gas emission
intensity of the B, C, and PAM treatments decreased by 35.20%, 26.65%, and
13.36%, respectively. The maize yield with the B and C treatments was
significantly increased by 11.33% and 9.59%, respectively; and the economic
budget of net ecosystem was increased by 16.15% and 12.65%, respectively
(P<0.05). In summary, adding extra bentonite and biocarbon to the conventional
fertilization was an effective agricultural measure for improving crop yield and
reducing the global warming potential for the corn planting system in the Hetao
irrigation area.
PMID- 29965698
TI - [Effect of Organic Manure Substitution of Synthetic Nitrogen on Crop Yield and
N2O Emission in the Winter Wheat-Summer Maize Rotation System].
AB - Controlling agricultural greenhouse gas emissions, such as N2O, is important in
mitigating global climate warming. Through monitoring the dynamics of N2O
emission fluxes, we investigated the effect of organic nitrogen (N) substitution
of synthetic N on N2O emissions and the yield of winter wheat and summer maize in
the Guanzhong Plain of Shaanxi Province, China. The study involved six
treatments, consisting of no fertilizer (CK), synthetic N, phosphorus (P), and
potassium (K) fertilizers alone (NPK), 75% NPK+25% organic N through manure
(25%M), 50% NPK+50% organic N (50%M), 25% NPK+75% organic N (75%M), 100% organic
N (100%M). The results showed that the peak value of the N2O emission flux
appeared after fertilization, rainfall, and irrigation. In the wheat season, the
emission flux of N2O varied from -1.33 to 144.2 MUg.(m2.h)-1, with the highest
peak value in the NPK treatment. In the maize season, the emission flux of N2O
varied from 88.2 to 1800.1 MUg.(m2.h)-1, and the 50%M treatment showed the
highest peak value. The range in the total amount of N2O emissions from the
different treatments in the wheat-maize rotation system was 429.8-2632.1 g.hm-2,
and the amount for the treatments decreased in order as follows:50%M > 25%M > NPK
> 75%M > 100%M > CK. The yields of wheat, maize, or wheat plus maize were
significantly higher in the fertilized treatments compared to the CK. Organic
substitution treatments significantly increased wheat yield by 26.1% to 50.0%
relative to the NPK treatment. While the maize yield in 50%M and 75%M treatments
was similar to that in the NPK treatment, the 25%M and 100%M treatments showed
significantly lower yields than with the NPK treatment. The total yield of wheat
plus maize varied from 9166 to 17496 kg.hm-2, of which total yield was
significantly higher with 50%M and 75%M compared to NPK. Overall, the 75%M
treatment is the best measure to guarantee crop yield and to reduce N2O emissions
in the wheat-maize rotation system based on a one year study in the Guanzhong
plain of Shaanxi Province.
PMID- 29965699
TI - [Dynamics of Rice Photosynthesized Carbon Input and Its Response to Nitrogen
Fertilization at the Jointing Stage:13 C-CO2 Pulse-labeling].
AB - Photosynthesized carbon (C) is an important source of soil organic C in paddy
fields, and its input and distribution are affected by rice growth and soil
fertility. Fertilizer application plays an important role in rice growth. The 13C
pulse-labeling method was used to quantify the dynamics and distribution of input
photosynthesized C in the rice-(rhizosphere-and bulk-) soil system and its
response to nitrogen fertilizer (N) application. The results suggested that N
fertilization significantly increased the rice aboveground and the root biomass
and decreased the rice biomass root/shoot ratio. The amount of assimilated 13C
gradually decreased in the rice plants but gradually decreased over 0-6 days and
increased over 6-26 days in the rhizosphere and bulk soil during rice growth. N
fertilization significantly increased the amount of assimilated 13C in the
rhizosphere soil by 9.5%-32.6% compared with the control. In comparison to the
unfertilized treatment, the application of N fertilization resulted in higher
photosynthetic13C in rice aboveground and in the root by 24.5%-134.7% and 9.1%
106%, respectively. With the N fertilized and unfertilized treatments, 85.5%
93.2% and 91.3%-95.7%, respectively, of input photosynthetic 13C was distributed
in the rice plants. The results suggested that N fertilization significantly
affected the distribution of photosynthesized C in the rice-soil system (P<0.01).
After 26 days of pulse labeling, the distribution of photosynthetic 13C into rice
aboveground was increased by 13.4%, while the distribution into the rhizosphere
and bulk soil were decreased by 21.9% and 52.2%, respectively, in the N
fertilized treatments compared with the unfertilized treatments. Therefore, the N
application increased the distribution of photosynthesized carbon in the soil
rice system but decreased the accumulation in the rhizosphere and bulk soil. The
findings of this study provided a theoretical basis for our understanding of the
dynamic of photosynthetic C in the plant-soil system and the assimilation of the
soil organic matter pool in the paddy soil ecosystem.
PMID- 29965700
TI - [Profile Distribution of Soil Organic and Inorganic Carbon Under Different Land
Use Types in the Loess Plateau of Northern Shaanxi].
AB - Carbon storage in the Loess Plateau is affected by land use. In order to assess
the differences in soil organic carbon (SOC) and soil inorganic carbon (SIC)
under different land use patterns in deep soil profiles, we investigated the
distribution characteristics of SOC and SIC at 0-20.0 m soil depth at three
locations in the northern Shaanxi province (i.e., an economical plantation in
Mizhi, a reforestation area in Shenmu, and a wind break and sand fixation forest
district in Yuyang). The results showed that the order for SOC content
was:pruning jujube tree (2.00 g.kg-1) > jujube tree (1.54 g.kg-1) > Caragana
(0.97 g.kg-1) > degraded artificial grassland (0.81 g.kg-1) > pine forests (0.70
g.kg-1) > natural grass field (0.45 g.kg-1), which indicated significant
differences between SOC content and land use types (P<0.05). Similarly, the order
of SIC content was:pruning jujube tree (11.66 g.kg-1) > jujube tree (11.59 g.kg
1) > Caragana (9.62 g.kg-1) > degraded artificial grassland (8.07 g.kg-1) > pine
forests (4.32 g.kg-1) > natural grass field (0.47 g.kg-1). There were no
significant differences between SIC content and soil profiles under the
economical plantation of Mizhi and the reforestation area of Shenmu. There were
significant differences for SIC content between an artificial economic forest, an
area returning farmland to a forest (grass) profile, and a windbreak and sand
fixation forest (P<0.05). The SIC densities for pruning jujube tree, jujube tree,
Caragana, degraded artificial grassland, pine forest, and natural grass field
were 6.19, 7.71, 10.70, 10.78, 5.91, and 1.03 times that of its corresponding SOC
density, respectively. It has been concluded that the soil carbon storage was
significantly different for different land use patterns, and the SIC content was
much higher than the SOC content in the soil profile.
PMID- 29965701
TI - [Effect of Biochar on Ammonia Volatilization from Soils of Different Surface
Conditions].
AB - In order to explore the effect of biochar on the volatilization of ammonia in
different surface soils, through the field test method, the responsiveness
changes of ammonia volatilization, ammonium nitrogen, and urease were studied
under the influence of biochar and crop cultivation. The study set six
treatments:CK+, BC0.5+, and BC4.5+ (the biochar applied at 0, 0.5, 4.5 kg.(m2.a)
1, respectively, under the condition of crop cultivation), and CK-, BC0.5-, and
BC4.5- (the biochar applied at 0, 0.5, 4.5 kg.(m2.a)-1, respectively, under the
condition of bare land). The results showed that under the condition of crop
cultivation, the ammonia volatilization of the BC4.5+ and BC0.5+ treatments
increased in 4 days, then significantly decreased by 9.95%-61.80% and 7.97%
50.52% (P<0.05), respectively, with respect to CK+. However, compared with CK-,
the ammonia volatilization of the BC4.5- and BC0.5- treatments increased by
40.02%-93.15% and 28.09%-57.45% (P<0.05), respectively. For the same amount of
biochar application, the ammonia volatilization of the crop-planting soil was
significantly lower than that of the bare land, and BC4.5+ and BC0.5+ declined by
27.10%-92.10% and 13.17%-83.45%(P<0.05), respectively, compared with the BC4.5-
and BC0.5-, and there was no significant difference between CK+ and CK-. The
above results indicated that biochar-mediated soil ammonia volatilization was
inhibited by the surface cover. Moreover, with respect to CK+, the maximum
increase rates of the contents of ammonium nitrogen and urease in the BC4.5+ and
BC0.5+ treatments were orderly at 69.25% and 72.73% and 93.61% and 90.56%
(P<0.05), but the soil ammonia volatilization decreased in the same period. The
biggest decline of the soil NH4+-N and urease content of BC4.5- and BC0.5- were
63.78% and 95.70% and 78.38% and 92.64% (P<0.05), respectively. Simultaneously,
the soil ammonia volatilization rose in the bare land compared with CK-.
Therefore, the soil ammonia volatilization was inversely related to soil NH4+-N
and urease under the influence of biochar, and the effect of crop planting was
more profound.
PMID- 29965702
TI - [Effects of Straw and Biochar Return in Soil on Soil Aggregate and Carbon
Sequestration].
AB - The aim of this work is to understand the effects of straw and biochar return in
soil on the content, distribution, stability, and relative contribution rate of
organic carbon for soil aggregates, which could be used to better understanding
the stability of the soil carbon pool and the protection mechanisms under straw
and biochar return. In this study, a field experiment was conducted to study the
effects of straw and biochar return on soil aggregates and carbon sequestration
characteristics in a rape-maize rotation planting system. Five treatments,
including a control (no organic material added, CK), straw (CS), straw and
microorganism (CSD), Biochar (BC), half straw and half biochar (CSBC), were used.
The results indicated that 1 Straw and biochar could improve the content of soil
organic carbon, and the BC and CSBC treatments increased it by 16.88-17.37 g.kg
1, values higher than those with the CS and CSD treatments (13.76-14.68 g.kg-1);
2 Compared with the CK treatment, CS and CSD treatments could increase the
stability of the aggregates through significantly increasing the content of macro
aggregate by 94.00%-117.78% and significantly increasing the mean weight diameter
(MWD), geometric mean diameter (GMD), and R0.25 of water stable aggregates, but
reducing the D value (P<0.05); and 3 With the increase in aggregate particle
size, the content of organic carbon in the aggregates decreased first and then
increased. The contribution rate of soil organic carbon in silt and clay was the
highest (29.61%-42.18%), and the contribution rate of organic carbon in the macro
aggregate was the lowest (9.19%-17.81%). In addition to the CSD treatment, the
CS, BC, and CSBC treatments reduced the contribution of larger aggregates (2-0.25
mm) and micro-aggregates (0.25-0.053 mm). In general, the benefit of straw return
was better than that of biochar in promoting soil aggregation. However, the
application of biochar was better than straw in improving the aggregates organic
carbon content. The newly generated carbon from straw degradation was mainly
distributed in large aggregates. Straw with microorganisms could promote the
combination of carbon by different components in the larger aggregates. The
carbon from biochar and straw with biochar treatments were mainly concentrated in
micro-aggregates.
PMID- 29965703
TI - [Assessment of the Availability of Soil Copper and Related Influencing Factors at
a County Scale].
AB - Understanding the spatial distribution of total copper, available copper, and the
spatial non-stationary relationships between available copper and relevant
environmental factors is important for the delineation of soil risk areas and the
development of related control measures. This study was conducted in Zhangjiagang
County of Jiangsu Province, China. The risk status for soil copper was assessed
based on 357 soil samples in the study area. The effects of soil type and land
use type on the concentration of available soil copper were discussed first.
Then, ordinary kriging was adopted to map the spatial distribution patterns of
the total soil copper and available soil copper, and the spatial distribution map
of the copper availability ratio (i.e., available copper/total copper) was also
developed for the study area. The risk areas for soil copper were delineated
based on the spatial distribution patterns of available soil copper and the
copper availability ratio. Finally, a new spatial local regression technique,
geographic weighted regression (GWR), was used to explore the local spatial
regression relationships between available copper and its three main impact
factors (i.e., total soil copper, soil pH, and SOM). Results showed that both
soil type and land-use type had some effect on the concentration of available
soil copper. The copper availability ratio had a strong spatial heterogeneity,
with the higher values mainly in the northeast, southeast, and northwest of the
study area and the lower values mainly in the middle and southwest of the study
area. The range of the copper availability ratio is 13.56% to 29.15%. The results
of the comparison of the traditional ordinary least squares regression (OLSR) and
GWR showed that the GWR model had higher fitting accuracy than the OLSR
model[i.e., a larger decision coefficient R2, and smaller corrected Akaike
information criteria (AICc) and the sum of squares of residuals] in modeling the
relationships between available copper and its three main impact factors. The GWR
analysis showed that the effect of soil factors on the concentration of soil
available copper was non-stationary. The GWR could effectively reveal the spatial
non-stationary influence of the related soil factors on the concentration of
available soil copper, and the results could explain the reasons for the
accumulation of available soil copper in local areas. Potential risk areas for
available soil copper were delineated based on the copper availability ratio and
the concentration of available soil copper in the study area. The results should
be crucial data for developing specific control measures for soil copper at a
regional scale.
PMID- 29965704
TI - [Application of the LUR Model in the Prediction of Spatial Distributions of Soil
Heavy Metals].
AB - Using the Jintan District of Changzhou City, Jiangsu Province as an example, the
LUR model was used to study the spatial distribution of heavy metals and to
simulate the spatial distribution of heavy metals in the study area. Compared
with the traditional LUR model and the ordinary Kriging interpolation model, the
following conclusions were obtained. 1 The soil heavy metal content in the study
area was highly and significantly correlated with land factors, with the main
factor of land use and influencing factors of heavy metals in the soil
environment (P<0.01). In terms of influencing factors, the soil Cu and Zn
contents were significantly correlated with the area related to traffic in a 2000
m buffer area and 2000 m buffer zone, respectively. The soil Cr, Cu, and Zn
contents were significantly correlated with OM, Corg, TC, and TN (P<0.01). 2 The
R2 of the LUR-S models of the spatial distribution of the heavy metals, Pb, Cr,
Cu, and Zn, in the study area were improved by 0.041, 0.406, 0.102, and 0.501,
respectively, compared with the traditional LUR model. The accuracy test R2
values were improved by 0.1477, 0.0116, 0.2310, and 0.081, respectively; and the
RMSE was reduced by 2.413, 0.631, 1.112, and 2.138, respectively. It was shown
that the LUR-S model, which considered the source-sink relationship, had a higher
accuracy than the traditional LUR model and ordinary Kriging interpolation model.
3 The LUR-S model was more suitable for the prediction of the spatial
distribution of heavy metals with lower pollution and smaller variations, while
results for the prediction of the heavy metals with higher pollution and larger
variations were worse.
PMID- 29965705
TI - [Pollution Characteristics and Source Apportionment of Polycyclic Aromatic
Hydrocarbons in Soils of Shenyang North New Area].
AB - Topsoil (0-20 cm) samples (n=101) in 5 different land use types in Shenyang North
New Area (SNNA), Shenyang, China were collected using the uniform grid layout
method to investigate the spatial distribution characteristics, composition
spectrum, and source analysis of 16 polycyclic aromatic hydrocarbons (PAHs)
listed as priority pollutants by the Environmental Protection Agency of the
United States. Results showed that the total concentration of the 16 PAHs
(SigmaPAHs) in soils of SNNA ranged from 123.7 MUg.kg-1 to 932.5 MUg.kg-1. The
PAH components were mainly dominated by 3-ring and 4-ring PAHs, of which the
proportion of 3-ring PAHs was the highest. The spatial distribution of the
SigmaPAHs concentration was obvious, showing a decreasing tendency from south to
north and from east to west. In the five soil types, the average concentrations
of the SigmaPAHs were relatively higher in the urban green space and the
artificial forest, followed by the vegetable land, while the total PAH
concentrations in paddy fields and corn fields were relatively lower and had no
obvious spatial distribution differences. Source apportionment results studied
using characteristic ratio analysis and factor analysis/multivariate linear
regression showed that the main sources of PAHs in the topsoil of SNNA were mixed
sources. Industrial coal combustion and motor vehicle exhaust were the main PAH
contributors, with a combined contribution rate of 79.6%. The oil spill and coke
oven contribution rate was about 16.2%, and the biomass fuel combustion was about
4.2%.
PMID- 29965706
TI - [Passivation of Simulated Pb-and Cd-Contaminated Soil by Applying Combined
Treatment of Phosphate, Humic Acid, and Fly Ash].
AB - In this study, three kinds of amendments including superphosphate, humic acid,
and fly ash and their complex combination were adopted to passivate the
artificially simulated Pb-and Cd-containing soils. The passivation efficiency
evaluation was performed via the CaCl2 and triethylenetriaminepentaacetic acid
(DTPA) extraction method as well as a BCR morphological classification
experiment. The microstructures and structures of the soil were explored further
via X-ray diffraction (XRD) and scanning electron microscopy with X-ray energy
dispersive spectroscopy (SEM-EDS) to elaborate the passivation mechanism. The
results demonstrated that all passivation processes, excluding single humic acid
addition, could reduce the CaCl2 and DTPA extraction contents of Pb and Cd in
soils, where the optimal efficiency could be achieved by the sequential addition
of superphosphate and humic acid, followed by fly ash. There was a weakly
positive correlation between soil pH and CaCl2/DTPA extraction content of Pb, a
negative correlation between soil pH and CaCl2/DTPA extraction content of Cd, and
a significantly negative correlation between available phosphorous content and
CaCl2/DTPA extraction contents of Pb and Cd, suggesting the crucial role of
available phosphorous contents to control the activities of Pb and Cd. In the
presence of phosphate, humic acid, and fly ash, the Pb and Cd could convert from
active weak acid extraction to low-activity residual speciation, resulting in
effectively reducing Pb and Cd transferability. Throughout the XRD and SEM-EDS
analyses, it was found that ion exchange was the predominant mechanism in heavy
metal passivation by single superphosphate, wherein the heavy metals were
transformed into an insoluble Ca-containing phosphate mixture. The
dissolving/precipitation or surface adsorption could be concluded as the main
mechanism in the combination of the three passivation agents that converted heavy
metals to lead phosphate precipitate[(Pb3(PO4)2] or mixed heavy metal
mineral[PbFe3(SO4)(PO4)(OH)6], so as to obtain superior heavy metal passivation
achievement.
PMID- 29965707
TI - [Distribution and Accumulation of Cadmium in Paddy Soil and Rice Affected by
Pollutant Sources Control and Improvement Measures].
AB - The objective of this study was to determine the effect of five scenarios on the
accumulation of Cd in the soil-rice system, including the return of straw to the
field and the lack of the return, atmospheric deposition control, use of clean
water for irrigation, and the use of lime. For the field experiments, three
typical paddies were selected and divided into five plots (5 m*6 m) in Xiangtan,
Zhuzhou, and Liling in the Hunan province from April to October 2016. The results
showed that the application of lime can increase pH by 0.87, while the available
Cd concentration in the soil was decreased by 33.7%. The accumulations of Cd in
roots, stems, and brown rice were decreased by 47.9%, 46.7%, and 54.8%,
respectively, with a decrease in the corresponding bioconcentration factors.
Irrigating with clean water and liming tended to increase the soil pH by 0.44 and
0.49, respectively, while the available Cd concentration in the soil was
decreased by 18.2% and 14.5%, respectively. The Cd concentrations in roots,
stems, and brown rice were decreased by 32.6%, 24.2%, and 18.0%, and 17.6%,
11.3%, and 25.4% with decreased bioconcentration factors under both treatments
(irrigating with clean water and liming). The available Cd concentration in the
soil was increased by 6.1% and the Cd accumulation in the rice plants also
increased with the return of straw to the soil. The bioconcentration factors of
the rice plants were also increased when the paddy straw was returned to the
fields. The results showed that the measures, such as the use of lime,
atmospheric deposition control, use of clean water for irrigation, and lack of
the return of straw to the paddy soil, should be helpful for the safe production
of brown rice. The possible long-term risks associated with returning straw to
the paddy field should be evaluated scientifically.
PMID- 29965708
TI - [Differences in Cd Accumulation in Typical Soils Under the Double Rice System].
AB - Pot experiments were used to study the differences of Cd uptake and accumulation
in double-cropping rice in typical soil types. To analyze the soil availability
of Cd (DTPA-Cd) in soils and the Cd accumulation in double-cropping rice at
different growth stages of the rice, we conducted pot experiments that selected
the yellow clayey soil (paddy soil developed from plate shaley parent materials)
and the granitic sandy soil (paddy soil developed from granitic parent
materials). Exogenous Cd was added with gradients of 0, 0.5, 1.0, 2.0, 5.0, and
10.0 mg.kg-1. Results showed that, during the rice growth period, the available
Cd in the yellow clayey soil was higher than that in the granitic sandy soil, and
the difference was significant (P<0.01). This showed that the content of Cd in
rice (roots, shoots, leaves, rice shells, and brown rice) increased along with
the treatment level and with the extension of the rice growth period. The
accumulation characteristics of Cd in rice grains and other tissues of rice
indicated differences between two seasons and two soil types, that is, late rice
was higher in Cd than was early rice, and reddish yellow clayey soil was higher
in Cd than granitic sandy soil. Significant positive linear correlations were
found between the effective contents of Cd in soils and those in rice tissues
(roots, shoots, leaves, and brown rice). The prediction model of Cd in rice and
the characteristic equation for rice accumulation of Cd were applied to calculate
the critical values of Cd:0.98 mg.kg-1 for early rice and 0.83 mg.kg-1 for late
rice in reddish yellow clayey soil, and 0.86 mg.kg-1 for early rice and 0.56
mg.kg-1 for late rice in granitic sandy soil. These threshold values are higher
than the National Standards given in "farmland environmental quality evaluation
standards for edible agricultural products (HJ 332-2006)." The soil security
threshold values and the soil environmental capacities of the two different
parent materials varied greatly; therefore, different environmental quality
standards may be formulated and different measures may be needed to control Cd
pollution in different parent materials.
PMID- 29965710
TI - [Effect of Nitrate Amendment on Soil Denitrification Activity and Anthracene
Anaerobic Degradation].
AB - The degradation of soil polycyclic aromatic hydrocarbons (PAHs) under
denitrification is one of the most important pathways for anaerobic PAH
elimination, but little is known about the effect of nitrate (the terminal
electron acceptor for denitrification) on soil denitrification activity and PAH
degradation under anaerobic conditions. In this study, the effect of nitrate on
soil anthracene anaerobic degradation and denitrification activity was
investigated through an anaerobic microcosm experiment. Two groups of treatments
without (N0) and with (N30) nitrate (30 mg.kg-1) amendment were conducted. Each
group contained three treatments with different anthracene concentrations (0, 15,
and 30 mg.kg-1, denoted as A0, A15, and A30, respectively). Therefore, a total of
six treatments (N0A0, N0A15, N0A30, N30A0, N30A15, and N30A30) were incubated in
darkness at 25C for 45 days, and the production rates of N2O and CO2, abundances
of denitrification related genes (narG:periplasmic nitrate reductase gene;
nirK:copper-containing nitrite reductase gene; and nirS:cd1-nitrite reductase
gene), and soil anthracene content were measured at 3, 7, 14, and 45 days. The
results indicated that the intensive denitrification enzyme activity in each
treatment was only detected at day 3, which could be significantly enhanced by
both nitrate and anthracene amendments. Subsequently, a sharp decline of
denitrification enzyme activity was observed in each treatment, while anthracene
showed an obvious inhibition of soil denitrification enzyme activity. The result
of a two-way ANOVA also indicated that nitrate, anthracene, and their
interactions had significant effects on soil denitrification enzyme activity. The
result of a quantitative-PCR indicated that, during the incubation, the
abundances of narG and nirS exhibited an increasing tendency, but the abundance
of nirK was relatively constant compared with its former counterparts. The final
removal rate of anthracene under anaerobic soil environment was in the range of
33.83%-55.01%, and neither the final removal rate nor the degradation rate of
anthracene could be significantly affected by nitrate amendment during
incubation. The anthracene degradation rates in the higher anthracene containing
treatments (N0A30 and N30A30) were significantly higher than those in the lower
anthracene containing treatments (N0A15 and N30A15). In summary, nitrate
amendments had no effect on soil anthracene anaerobic degradation but could
significantly affect soil denitrification enzyme activity and the abundance of
denitrification related narG and nirS genes.
PMID- 29965709
TI - [Distribution Characteristics of Mercury in Reed Leaves from the Jiapigou Gold
Mine in the Songhua River Upstream].
AB - At the Jiapigou gold mine of the Songhua River upstream, reed leaves (Phragmites
australis), soil, and water samples were collected from June (summer) and
September (autumn) 2016 for the determination of mercury. Moreover, the mercury
concentrations in the air were determined synchronously. Furthermore, the level
of mercury pollution in the reed leaves was determined by a single factor
pollution index method, and the relationships among mercury concentrations in the
reed leaves and environmental factors were analyzed to research the distribution
characteristics, influencing factors, and correlations around the gold mining
area. The results show that, in terms of spatial distribution, the mercury
concentrations in reed leaves, soil, and water gradually decay with the distance
from the gold mining area, and the spatial distribution of the mercury
concentrations in the air was not obvious. Regarding a temporal distribution, the
mercury concentrations in the reed leaves in summer were lower than those in
autumn in the heavy pollution areas, while the distribution in the light
pollution areas was the opposite, as the mercury concentrations of air and soil
in summer were higher than those in autumn. The influence of environmental
factors on the mercury concentrations in the reed leaves was soil > air > water.
In addition, after stopping gold mining and processing using mercury, the mercury
source in the area was the soil.
PMID- 29965711
TI - [Effects of Long-term Fertilization Regimes on Microbial Biomass, Community
Structure and Activity in a Paddy Soil].
AB - Four paddy soils were collected in Ningxiang County, Hunan province. These used
with different long-term fertilization regimes, including a control without
fertilizer (CK), chemical fertilization with nitrogen, phosphate, and kalium
(NPK), straw fertilization combined with NPK (ST), and manure fertilization
combinedwith NPK (OM). Phospholipid fatty acid (PLFA) technology and MicrorespTM
method were used to study the effect of long-term fertilization on soil
microorganism abundance, community structure, and activity. Results showed that
the abundance of bacteria, fungi, gram-negative (G-) bacteria, and gram-positive
(G+) bacteria in the soil from the OM treatment was generally higher than for the
other treatments; these levels were lower in the ST and NPK treatments and lowest
in the CK treatment. The principal components analysis (PCA) of PLFA showed that
the community structure of microorganisms in NPK, ST, and OM treatments was
altered in comparison with that in CK, especially in the case of the ST and OM
treatments. MicroRespTM results revealed that compared to the CK treatment (1.28
MUg.h-1), soil microorganisms in the OM treatment had the highest average
utilization rate of multiple carbon sources (1.81 MUg.h-1), followed by ST (1.19
MUg.h-1), CK (1.28 MUg.h-1), and NPK (0.95 MUg.h-1). Furthermore, different long
term fertilization regimes resulted in distinct carbon source preferences for the
soil microorganisms and revealed a significant alteration in the microbial
community. Conclusively, long-term fertilizer with straw or manure changes the
microbial community and is a benefit for improving the biomass and activity of
microorganism in rice paddy soils.
PMID- 29965712
TI - [Analysis of Sulfate-Reducing and Sulfur-Oxidizing Prokaryote Community
Structures in Marine Sediments with Different Sequencing Technologies].
AB - Sulfate-reducing prokaryotes (SRP) and sulfur-oxidizing prokaryotes (SOP) play
vital roles in the sulfur cycle. The SRP community was used to represent a
microbial community with high richness and diversity. The 454 pyrosequencing,
Illumina high-throughput sequencing, and traditional clone library methods that
target the dissimilatory sulfite reductase beta subunit gene (dsrB), which
encodes a key enzyme in the sulfate reduction pathway, were used to compare the
differences in SRP community characteristics. Comparative analyses suggested that
Illumina high-throughput sequencing was a more appropriate method for SRP (high
richness and diversity) community studies. The SOP soxB gene (~750 bp) was used
as a representative of the long-sequence segment. The 454 pyrosequencing and
Illumina high-throughput sequencing methods were used to compare the differences
in SOP community characteristics. The results revealed that 454 pyrosequencing
did not reflect its advantage of a longer read length; whereas, the Illumina high
throughput sequencing with more numerous and shorter sequence reads was more
suitable when the soxB gene was used to investigate the community composition and
diversity of SOP.
PMID- 29965713
TI - [Seasonal and Spatial Variations of Microcystins and Their Relationships with
Physiochemical and Biological Factors in Poyang Lake].
AB - Poyang Lake is the largest freshwater lake in China and an important drinking
water source for Jiangxi Province. Since the year 2000, toxic cyanobacteria have
been observed frequently in Poyang Lake. In this study, water samples were
collected in the lake quarterly (April 2012, August 2012, October 2012, and
January 2013) to examine the spatial and seasonal variations in the
concentrations of microcystins (MCs; MC-RR, -YR, and -LR) and their relationships
with physiochemical and biological factors. MCs were determined by ultra-high
performance liquid chromatography-electrospray ionization tandem triple
quadrupole/mass spectrometry (UPLC-MS/MS). MC-RR (accounting for 75.01% and
71.34% of intracellular MC (IMC) and extracellular MC (EMC) concentrations,
respectively) was the most dominant variant in Poyang Lake, followed by MC-LR
(accounting for 21.95% and 24.97% of IMC and EMC concentrations, respectively),
while MC-YR was detected in low concentrations (accounting for 3.01% and 3.69% of
IMC and EMC concentrations, respectively). Total MC concentrations (IMC + EMC,
TMC) ranged from 0.49 to 3517.85 ng.L-1, with an average of 337.43 ng.L-1 and
only 2.53% (2 out of 79 water samples) of the water samples contained MCs
concentrations exceeding the drinking water guideline level of 1 ng.L-1 for MC-LR
proposed by World Health Organization (WHO). IMC concentrations showed
significant relationships with Microcystis biomass (r=0.47, P<0.01), Oscillatoria
biomass (r=0.68, P<0.01), Cyanobacteria biomass (r=0.56, P<0.01), and Chl-a
(r=0.28, P<0.01), but no significant correlation was found between intracellular
MC concentration and Anabena biomass (P>0.05), suggesting that Microcystis and
Oscillatoria might be the main MCs-producing cyanobacteria in Poyang Lake. In
addition, IMC concentrations were positively correlated with water temperature
(r=0.51, P<0.01), transparence (r=0.69, P<0.01), Fe (r=0.43, P<0.01), and Zn
contents (r=0.43, P<0.01), and negatively correlated with TN (r=-0.44, P<0.01),
TP (r=-0.29, P<0.01), NH4+-N (r=-0.33, P<0.05), NO2--N (r=-0.28, P<0.05), Ca (r=
0.34, P<0.01), and Mg(r=-0.35, P<0.05), while no significant correlations were
observed between IMC concentrations and pH, PO43--P, NO3--N, electrical
conductivity, permanganate index, and Cu content (P>0.05). These results
indicated that light intensity (represented by transparence), nitrogen,
phosphorus, and water temperature might be the regulating factors of MCs
production in Poyang Lake and trace elements (Fe, Zn, Ca, and Mg) can influence
the MC production to a certain extent. IMCs and EMCs exhibited similar seasonal
variations in Poyang Lake. The highest values of IMCs (531.87 ng.L-1) and EMCs
(232.44 ng.L-1) were observed in summer. The concentrations of IMCs and EMCs in
autumn were 31.97 ng.L-1 and 6.49 ng.L-1, respectively. Low concentrations were
observed in spring (0.55 ng.L-1 and 0.88 ng.L-1 of IMCs and EMCs, respectively)
and winter (0.69 ng.L-1 and 4.14 ng.L-1 of IMCs and EMCs, respectively). The
highest IMCs and EMCs values of Poyang Lake in summer were 2298.08 ng.L-1 and
1219.77 ng.L-1, respectively, and the lowest values were 92.53 ng.L-1 and 38.80
ng.L-1, respectively. Overall, the concentrations of IMCs in eastern bays, the
vicinity of Songmen Mountain, Banghu Lake, and its outlet were higher than those
in other regions. However, the spatial distributions of EMCs in Poyang Lake were
different from those of IMCs. EMCs concentrations in the vicinity of Songmen
Mountain, Banghu Lake, and its outlet were higher than those in other regions.
PMID- 29965714
TI - [Distribution of Multidrug-Resistant Bacteria and Antibiotic-Resistant Genes in
Livestock Manures].
AB - In the present study, techniques for microbial culture enumeration, 16S rDNA gene
sequencing for bacterial identification, high-throughput sequencing for the
multidrug-resistant bacteria (MRB) communities, and high-throughput quantitative
PCR detection for the prevalence and abundance of antibiotic resistance genes
(ARGs) were conducted to investigate the distribution characteristics of MRB and
ARGs in chicken and swine manures. The results showed that the rates of MRB that
were resistant to tetracycline, ciprofloxacin, and gentamycin simultaneously were
from 7.96% to 12.40% for the different manure samples. The dominant genera of
cultivable MRB were Escherichia, Acinetobacter, and Proteus, both in the chicken
and swine manures. High-throughput quantitative PCR results indicated that,
compared to the antibiotic free swine manure, the total enrichment of ARGs
increased by 1.96*104-1.54*105 times that in the swine manure samples, with
different antibiotics following the sequence of tetracyclines > beta-lactams >
MLSB (macrolide, lincosamide, and streptogramin B) > aminoglycosides > FCA
(fluoroquinolone, quinolone, florfenicol, chloramphenicol, and amphenicol) >
sulfonamides > vancomycins.
PMID- 29965715
TI - [Influence of Air Pollution Control (APC) Systems and Furnace Type on the
Characteristics of APC Residues from Municipal Solid Waste Incinerators].
AB - The characteristics of air pollution control (APC) residues are influenced by the
furnace type, APC system, and waste composition. In this study, the
characteristics of APC residues from nine municipal solid waste incineration
plants (the compositions of incinerated solid waste are similar) with different
furnace types and APC systems were compared.APC residues contain a great amount
of Ca and Cl, and the contents of Al, Si, and Fe in the APC residues from
fluidized bed incinerators are higher. The mineral compositions of APC residues
are not influenced by the flue gas treatment process, but their contents vary.
The contents of Cd, Pb, and Zn in the APC residues from fluidized bed
incinerators are lower, while those of Cr, Ba, Cu, and Ni are greatly influenced
by the APC systems, with the "grate+dry scrubber" APC residues having the lowest
values. The differences in the heavy metal contents in the APC residues from two
incinerators before and after the upgrading of the APC systems are not
significant. The leaching toxicity of Pb in the APC residues from grate
incinerators is higher than that from fluidized bed incinerators, while some
elements with low contents in fluidized bed APC residues can be leached more in
acetic acid buffer solution. The acid neutralization capacity of the APC residues
is related to Ca content. The leaching concentrations of most heavy metals are
significantly increased under strong acidity (Cd, Ni, and Zn:leachate pH < 8; Pb,
Cu, and Cr:leachate pH < 4). The maximum leaching concentrations of As, Ba, Cu,
Ni, and Pb in the APC residues from grate incinerators are mainly controlled by
their total content. The leaching concentrations of As, Ba, Cu, Ni, and Pb in the
APC residues from fluidized bed incinerators are lower than those from grate
incinerators with similar metal contents, which may be due to their different
chemical speciation influenced by furnace types and the complexation with Al and
Fe compounds.
PMID- 29965719
TI - Electrochemical Synthesis of Mesoporous Au-Cu Alloy Films with Vertically
Oriented Mesochannels Using Block Copolymer Micelles.
AB - We synthesized Au-Cu bimetallic alloy films with a controlled mesoporous
architecture through electrochemical deposition using an electrolyte solution
containing spherical polymeric micelles. The composition of the alloy films can
be easily controlled by tuning the ratio between the Au and Cu species present in
the electrolyte solution. At low Cu content, cage-type mesopores are formed,
reflecting the parent micellar template. Surprisingly, upon increasing the Cu
content, the cage-type mesopores fuse to form vertically aligned one-dimensional
mesochannels. The vertical alignment of these mesopores is favorable for enhanced
mass and ion transfer within the channels due to low diffusion resistance. The
atomic distribution of Au and Cu is uniform over the entire film and free of any
phase segregation. The as-synthesized mesoporous Au-Cu films exhibit excellent
performance as a nonenzymatic glucose sensor with high sensitivity and
selectivity, and the current response is linear over a wide range of
concentrations. This work identifies the properties responsible for the promising
performance of such mesoporous alloy films for the clinical diagnosis of
diabetes. This micelle-assisted electrodeposition approach has a high degree of
flexibility and can be simply extended from monometallic compounds to a
multimetallic system, enabling the fabrication of various mesoporous alloy films
suitable for different applications.
PMID- 29965720
TI - Molecular Layer Deposition of a Highly Stable Silicon Oxycarbide Thin Film Using
an Organic Chlorosilane and Water.
AB - In this study, molecular layer deposition (MLD) was used to deposit ultrathin
films of methylene-bridged silicon oxycarbide (SiOC) using
bis(trichlorosilyl)methane and water as precursors at room temperature. By
utilizing bifunctional trichlorosilane precursors, films of SiOC can be deposited
in a layer-by-layer manner, wherein a water co-reactant circumvents the need for
plasma, high temperatures, or highly oxidizing precursors. In this manner, films
could be grown without the degradation commonly seen in other SiOC deposition
methods. Saturation behavior for both precursors was confirmed for the MLD
process, and a constant growth rate of 0.5 +/- 0.1 A/cycle was determined. X-ray
photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy were
used to verify the reaction between precursors and to gain insight into the final
film composition. Unlike most MLD films, which grow polymers in a linear fashion,
XPS analysis indicates that neighboring silanol groups within the films tend to
condense, forming a highly cross-linked network structure, whereby, on average,
two-thirds of silanol groups undergo a condensation reaction. Further indication
of cross-linking is seen by XPS during in situ annealing, which shows exceptional
temperature stability of the film up to 600 degrees C in vacuum, in contrast to
linear SiOC films, which are known to degrade below this temperature. The films
also exhibit high chemical stability against acids, bases, and solvents. A film
density of 1.4 g/cm3 was measured by X-ray reflectivity, while the dielectric
constant and refractive index were determined to be 2.6 +/- 0.3 and 1.6 +/- 0.1,
respectively, at a 633 nm wavelength. The low dielectric constant, high ease of
deposition, and exceptional thermal and chemical stabilities of this MLD SiOC
film suggest that it may have potential applications for electronic devices.
PMID- 29965721
TI - Electrochromic-Tuned Plasmonics for Photothermal Sterile Window.
AB - Electrochromic materials are widely used in smart windows. An ideal future
electrochromic window would be able to control visible light transmission, tune
building's heat conversion of near-infrared (NIR) solar radiation, and reduce
attacks by microorganisms. To date, most of the reports have primarily focused on
visible-light transmission modulation using electrochromic materials. Herein, we
report the fabrication of an electrochromic-photothermal film by integrating
electrochromic WO3 with plasmonic Au nanostructures and demonstrate its
adjustability during optical transmission and photothermal conversion of visible
and NIR lights. The localized surface plasmon resonance (LSPR) of Au
nanostructures and the broadband nonradiative plasmon decay are proposed to be
tunable using both the electric field and the WO3 substrate. Further enhanced
photothermal conversion is achieved in colored state, which is attributed to
coupling of traditional visible-band optical switching with NIR-LSPR extinction.
The resulted electrochromic-photothermal film can also effectively reduce the
numbers of attacking microorganisms, thus promising for use as a sterile smart
window for advanced applications.
PMID- 29965722
TI - Cycling of Rational Hybridization Chain Reaction To Enable Enzyme-Free DNA-Based
Clinical Diagnosis.
AB - In order to combat the growing threat of global infectious diseases, there is a
need for rapid diagnostic technologies that are sensitive and that can provide
species specific information (as might be needed to direct therapy as resistant
strains of microbes emerge). Here, we present a convenient, enzyme-free
amplification mechanism for a rational hybridization chain reaction, which is
implemented in a simple format for isothermal amplification and sensing, applied
to the DNA-based diagnosis of hepatitis B virus (HBV) in 54 patients. During the
cycled amplification process, DNA monomers self-assemble in an organized and
controllable way only when a specific target HBV sequence is present. This
mechanism is confirmed using super-resolution stochastic optical reconstruction
microscopy. The enabled format is designed in a manner analogous to an enzyme
linked immunosorbent assay, generating colored products with distinct tonality
and with a limit of detection of ca. five copies/reaction. This routine assay
also showed excellent sensitivity (>97%) in clinical samples demonstrating the
potential of this convenient, low cost, enzyme-free method for use in low
resource settings.
PMID- 29965723
TI - Combined Modification of Dual-Phase Li4Ti5O12-TiO2 by Lithium Zirconates to
Optimize Rate Capabilities and Cyclability.
AB - The low electrical conductivity and ordinary lithium-ion transfer capability of
Li4Ti5O12 restrict its application to some degree. In this work, dual-phase
Li4Ti5O12-TiO2 (LTOT) was modified by composite zirconates of Li2ZrO3, Li6Zr2O7
(LZO) to boost the rate capabilities and cyclability. When the homogeneous
mixture of LiNO3, Zr(NO3)4.5H2O and LTOT was roasted at 700 degrees C for 5 h,
the obtained composite achieved a superior reversible capacity of 183.2 mAh g-1
to the pure Li4Ti5O12 after cycling at 100 mA g-1 for 100 times due to the
existence of a scrap of TiO2. Meanwhile, when the composite was cycled by
consecutively doubling the current density between 100 and 1600 mA g-1, the
corresponding reversible capacities are 183.2, 179.1, 176.5, 173.3, and 169.3 mAh
g-1, signifying the prominent rate capabilities. Even undergoing 1400
charge/discharge cycles at 500 mA g-1, a reversible capacity of 144.7 mAh g-1 was
still attained, denoting splendid cyclability. From a series of comparative
experiments and systematic characterizations, the formation of LZO meliorated
both the Li+ migration kinetics and electrical conductivity on account of the
concomitant superficial Zr4+ doping, responsible for the comprehensive elevation
of the electrochemical performance.
PMID- 29965724
TI - In Vivo Tracking and 1H/19F Magnetic Resonance Imaging of Biodegradable
Polyhydroxyalkanoate/Polycaprolactone Blend Scaffolds Seeded with Labeled Cardiac
Stem Cells.
AB - Medium-chain length polyhydroxyalkanoates (MCL-PHAs) have demonstrated
exceptional properties for cardiac tissue engineering (CTE) applications. Despite
prior work on MCL-PHA/polycaprolactone (PCL) blends, optimal scaffold production
and use as an alternative delivery route for controlled release of seeded cardiac
progenitor cells (CPCs) in CTE applications in vivo has been lacking. We present
herein applicability of MCL-PHA/PCL (95/5 wt %) blends fabricated as thin films
with an improved performance compared to the neat MCL-PHA. Polymer
characterization confirmed the chemical structure and composition of the
synthesized scaffolds, while thermal, wettability, and mechanical properties were
also investigated and compared in neat and porous counterparts. In vitro
cytocompatibility studies were performed using perfluorocrown-ether-nanoparticle
labeled murine CPCs and studied using confocal microscopy and 19F magnetic
resonance spectroscopy and magnetic resonance imaging (MRI). Seeded scaffolds
were implanted and studied in the postmortem murine heart in situ and in two
additional C57BL/6 mice in vivo (using single-layered and double-layered
scaffolds) and imaged immediately after and at 7 days postimplantation. Superior
MCL-PHA/PCL scaffold performance has been demonstrated compared to MCL-PHA
through experimental comparisons of (a) morphological data using scanning
electron microscopy and (b) contact angle measurements attesting to improved CPC
adhesion, (c) in vitro confocal microscopy showing increased SC proliferative
capacity, and (d) mechanical testing that elicited good overall responses. In
vitro MRI results justify the increased seeding density, increased in vitro MRI
signal, and improved MRI visibility in vivo, in the double-layered compared to
the single-layered scaffolds. Histological evaluations [bright-field, cytoplasmic
(Atto647) and nuclear (4',6-diamidino-2-phenylindole) stains] performed in
conjunction with confocal microscopy imaging attest to CPC binding within the
scaffold, subsequent release and migration to the neighboring myocardium, and
increased retention in the murine myocardium in the case of the double-layered
scaffold. Thus, MCL-PHA/PCL blends possess tremendous potential for controlled
delivery of CPCs and for maximizing possible regeneration in myocardial
infarction.
PMID- 29965725
TI - Micelle-Forming Dexamethasone Prodrug Attenuates Nephritis in Lupus-Prone Mice
without Apparent Glucocorticoid Side Effects.
AB - Nephritis is one of the major complications of systemic lupus erythematosus.
While glucocorticoids (GCs) are frequently used as the first-line treatment for
lupus nephritis (LN), long-term GC usage is often complicated by severe adverse
effects. To address this challenge, we have developed a polyethylene glycol-based
macromolecular prodrug (ZSJ-0228) of dexamethasone, which self-assembles into
micelles in aqueous media. When compared to the dose equivalent daily
dexamethasone 21-phosphate disodium (Dex) treatment, monthly intravenous
administration of ZSJ-0228 for two months significantly improved the survival of
lupus-prone NZB/W F1 mice and was much more effective in normalizing proteinuria,
with clear histological evidence of nephritis resolution. Different from the dose
equivalent daily Dex treatment, monthly ZSJ-0228 administration has no impact on
the serum anti-double-stranded DNA (anti-dsDNA) antibody level but can
significantly reduce renal immune complex deposition. No significant systemic
toxicities of GCs ( e. g., total IgG reduction, adrenal gland atrophy, and
osteopenia) were found to be associated with ZSJ-0228 treatment. In vivo imaging
and flow cytometry studies revealed that the fluorescent-labeled ZSJ-0228
primarily distributed to the inflamed kidney after systemic administration, with
renal myeloid cells and proximal tubular epithelial cells mainly responsible for
its kidney retention. Collectively, these data suggest that the ZSJ-0228's potent
local anti-inflammatory/immunosuppressive effects and improved safety may be
attributed to its nephrotropicity and cellular sequestration at the inflamed
kidney tissues. Pending further optimization, it may be developed into an
effective and safe therapy for improved clinical management of LN.
PMID- 29965727
TI - Integrating Proteins in Layer-by-Layer Assemblies Independently of their
Electrical Charge.
AB - Layer-by-layer (LbL) assembly is an attractive method for protein immobilization
at interfaces, a much wanted step for biotechnologies and biomedicine.
Integrating proteins in LbL thin films is however very challenging due to their
low conformational entropy, heterogeneous spatial distribution of charges, and
polyampholyte nature. Protein-polyelectrolyte complexes (PPCs) are promising
building blocks for LbL construction owing to their standardized charge and
polyelectrolyte (PE) corona. In this work, lysozyme was complexed with
poly(styrenesulfonate) (PSS) at different ionic strengths and pH values. The PPCs
size and electrical properties were investigated, and the forces driving
complexation were elucidated, in the light of computations of polyelectrolyte
conformation, with a view to further unravel LbL construction mechanisms. Quartz
crystal microbalance and atomic force microscopy were used to monitor the
integration of PPCs compared to the one of bare protein molecules in LbL
assemblies, and colorimetric assays were performed to determine the protein
amount in the thin films. Layers built with PPCs show higher protein contents and
hydration levels. Very importantly, the results also show that LbL construction
with PPCs mainly relies on standard PE-PE interactions, independent of the charge
state of the protein, in contrast to classical bare protein assembly with PEs.
This considerably simplifies the incorporation of proteins in multilayers, which
will be beneficial for biosensing, heterogeneous biocatalysis, biotechnologies,
and medical applications that require active proteins at interfaces.
PMID- 29965726
TI - Diameter-Dependent Optical Absorption and Excitation Energy Transfer from
Encapsulated Dye Molecules toward Single-Walled Carbon Nanotubes.
AB - The hollow cores and well-defined diameters of single-walled carbon nanotubes
(SWCNTs) allow for creation of one-dimensional hybrid structures by encapsulation
of various molecules. Absorption and near-infrared photoluminescence-excitation
(PLE) spectroscopy reveal that the absorption spectrum of encapsulated 1,3-bis[4
(dimethylamino)phenyl]-squaraine dye molecules inside SWCNTs is modulated by the
SWCNT diameter, as observed through excitation energy transfer (EET) from the
encapsulated molecules to the SWCNTs, implying a strongly diameter-dependent
stacking of the molecules inside the SWCNTs. Transient absorption spectroscopy,
simultaneously probing the encapsulated dyes and the host SWCNTs, demonstrates
this EET, which can be used as a route to diameter-dependent photosensitization,
to be fast (sub-picosecond). A wide series of SWCNT samples is systematically
characterized by absorption, PLE, and resonant Raman scattering (RRS), also
identifying the critical diameter for squaraine filling. In addition, we find
that SWCNT filling does not limit the selectivity of subsequent separation
protocols (including polyfluorene polymers for isolating only semiconducting
SWCNTs and aqueous two-phase separation for enrichment of specific SWCNT
chiralities). The design of these functional hybrid systems, with tunable dye
absorption, fast and efficient EET, and the ability to remove all metallic SWCNTs
by subsequent separation, demonstrates potential for implementation in
photoconversion devices.
PMID- 29965728
TI - Solid State NMR Studies of Intact Lipopolysaccharide Endotoxin.
AB - Lipopolysaccharides (LPS) are complex glycolipids forming the outside layer of
Gram-negative bacteria. Their hydrophobic and heterogeneous nature greatly
hampers their structural study in an environment similar to the bacterial
surface. We have studied LPS purified from E. coli and pathogenic P. aeruginosa
with long O-antigen polysaccharides assembled in solution as vesicles or
elongated micelles. Solid-state NMR with magic-angle spinning permitted the
identification of NMR signals arising from regions with different flexibilities
in the LPS, from the lipid components to the O-antigen polysaccharides. Atomic
scale data on the LPS enabled the study of the interaction of gentamicin
antibiotic bound to P. aeruginosa LPS, for which we could confirm that a specific
oligosaccharide is involved in the antibiotic binding. The possibility to study
LPS alone and bound to a ligand when it is assembled in membrane-like structures
opens great prospects for the investigation of proteins and antibiotics that
specifically target such an important molecule at the surface of Gram-negative
bacteria.
PMID- 29965729
TI - Near-Unity Efficiency Energy Transfer from Colloidal Semiconductor Quantum Wells
of CdSe/CdS Nanoplatelets to a Monolayer of MoS2.
AB - A hybrid structure of the quasi-2D colloidal semiconductor quantum wells
assembled with a single layer of 2D transition metal dichalcogenides offers the
possibility of highly strong dipole-to-dipole coupling, which may enable
extraordinary levels of efficiency in Forster resonance energy transfer (FRET).
Here, we show ultrahigh-efficiency FRET from the ensemble thin films of CdSe/CdS
nanoplatelets (NPLs) to a MoS2 monolayer. From time-resolved fluorescence
spectroscopy, we observed the suppression of the photoluminescence of the NPLs
corresponding to the total rate of energy transfer from ~0.4 to 268 ns-1. Using
an Al2O3 separating layer between CdSe/CdS and MoS2 with thickness tuned from 5
to 1 nm, we found that FRET takes place 7- to 88-fold faster than the Auger
recombination in CdSe-based NPLs. Our measurements reveal that the FRET rate
scales down with d-2 for the donor of CdSe/CdS NPLs and the acceptor of the MoS2
monolayer, d being the center-to-center distance between this FRET pair. A full
electromagnetic model explains the behavior of this d-2 system. This scaling
arises from the delocalization of the dipole fields in the ensemble thin film of
the NPLs and full distribution of the electric field across the layer of MoS2.
This d-2 dependency results in an extraordinarily long Forster radius of ~33 nm.
PMID- 29965730
TI - Nuclear Magnetic Resonance Solution Structure of the Recombinant Fragment
Containing Three Fibrin-Binding Cysteine-Rich Domains of the Very Low Density
Lipoprotein Receptor.
AB - Our previous studies revealed that interaction of fibrin with the very low
density lipoprotein (VLDL) receptor plays a prominent role in transendothelial
migration of leukocytes and thereby inflammation. The major goal of our
subsequent studies is to establish the structural basis for this interaction. As
the first step toward this goal, we localized the fibrin-binding sites within
cysteine-rich (CR) domains 2-4 of the VLDL receptor. In this study, we have made
a next step toward this goal by establishing the nuclear magnetic resonance
solution structure of the recombinant VLDLR(2-4) fragment containing all three
fibrin-binding CR domains of this receptor. The structure revealed that all three
CR domains have a similar general fold. Each domain contains a calcium-binding
loop, and the loop in the CR3 domain has a unique conformation relative to the
other two. Domains CR2 and CR3 interact with each other, while CR4 is flexible
relative to the other two domains. In addition, analysis of the electrostatic
potential surface of VLDLR(2-4) revealed extended negatively charged regions in
each of its CR domains. The presence of these regions suggests that they may
interact with three positively charged clusters of the fibrin betaN domain whose
involvement in interaction with the VLDL receptor was demonstrated earlier.
Altogether, these findings provide a solid background for our next step toward
establishing the structural basis for fibrin-VLDL receptor interaction.
PMID- 29965731
TI - Engineering Intravenously Administered Nanoparticles to Reduce Infusion Reaction
and Stop Bleeding in a Large Animal Model of Trauma.
AB - Bleeding from traumatic injury is the leading cause of death for young people
across the world, but interventions are lacking. While many agents have shown
promise in small animal models, translating the work to large animal models has
been exceptionally difficult in great part because of infusion-associated
complement activation to nanomaterials that leads to cardiopulmonary
complications. Unfortunately, this reaction is seen in at least 10% of the
population. We developed intravenously infusible hemostatic nanoparticles that
were effective in stopping bleeding and improving survival in rodent models of
trauma. To translate this work, we developed a porcine liver injury model.
Infusion of the first generation of hemostatic nanoparticles and controls 5 min
after injury led to massive vasodilation and exsanguination even at extremely low
doses. In naive animals, the physiological changes were consistent with a
complement-associated infusion reaction. By tailoring the zeta potential, we were
able to engineer a second generation of hemostatic nanoparticles and controls
that did not exhibit the complement response at low and moderate doses but did at
the highest doses. These second-generation nanoparticles led to cessation of
bleeding within 10 min of administration even though some signs of vasodilation
were still seen. While the complement response is still a challenge, this work is
extremely encouraging in that it demonstrates that when the infusion-associated
complement response is managed, hemostatic nanoparticles are capable of rapidly
stopping bleeding in a large animal model of trauma.
PMID- 29965732
TI - Modulation of the Coordination Environment around the Magnetic Easy Axis Leads to
Significant Magnetic Relaxations in a Series of 3d-4f Schiff Complexes.
AB - A series of Salen-type Zn(II)-Dy(III) complexes [L1Zn(II)ClDy(III)(acac)2].H2O
(1), [L1Zn(II)BrDy(III)(acac)2].H2O (2), [L1Zn(II)(H2O)Dy(III)(acac)2].CH2Cl2.PF6
(3), [L2Zn(II)(H2O)Dy(III)(acac)2].PF6 (4), and Co(III)-Dy(III) complexes
[L1Co(III)Br2Dy(III)(acac)2].CH2Cl2 (5), [L2Co(III)Cl2Dy(III)(acac)Cl(MeO)] (6),
[L2Co(III)Cl2Dy(III)(acac)Cl(H2O)] (7), and [L2Co(III)Cl2Dy(III)(NO3)2(MeO)] (8)
heterobinuclear single-molecule magnets (SMMs) were synthesized and magnetically
characterized. These complexes were constructed by incorporating diamagnetic
Zn(II) and Co(III) ions with acetylacetone (acac) and compartmental Schiff-base
ligands (H2L1 = N, N'-bis(2-oxy-3-methoxybenzylidene)-1,2-phenylenediamine; H2L2
= N, N'-bis(2-oxy-3-methoxybenzylidene)-1,2-diaminocyclohexane). In the Zn(II)
Dy(III) (1-4) system, the coordination environments of the Dy(III) ions are
nearly identical, but the apical coordination atom to the Zn(II) ion is
different. Complexes 1, 2, and 4 displayed no magnetic relaxation in the absence
of external magnetic field, but complex 3 displayed more pronounced SMM behavior
with a relaxation energy barrier Ueff/ kB 38 K and magnetic hysteresis at 1.8 K.
The SMM performances of 5, 6, and 7 were enhanced significantly by incorporating
an octahedral Co(III) instead of square-pyramidal Zn(II) and replacing one of
acac- group around Dy(III) ion by a neutral O atom, displaying Ueff of 167, 118,
and 75 K as well as magnetic hysteresis up to 3.5 K. These studies indicated that
the remote diamagnetic Zn(II) and Co(III) ions played a key role, and the SMM
properties were very strongly related to the special coordination atoms
configuration around Dy(III) ion. When this coordination configuration around was
broken as 8 exhibited, however, it resulted in a dramatically decreased SMM
performance. From this work, the key factors that significantly affect the SMM
performance of these heteronuclear Zn(II)/Co(III)-Dy(III) SMMs are unambiguously
presented.
PMID- 29965733
TI - Point Spread Function of Objective-Based Surface Plasmon Resonance Microscopy.
AB - Objective-based surface plasmon resonance microscopy (SPRM) is a novel optical
imaging technique that can map the spatial distribution of a local refractive
index based on propagating surface plasmon polaritons (SPPs). Different from some
other optical microscopy that shows a dot-like point spread function (PSF), a
nanosized object appears as a wave-like pattern containing parabolic tails in
SPRM. The geometrical complexity of the wave-like pattern hampered the
quantitative interpretation of the PSF of SPRM. Previous studies have shown that
two adjacent rings were obtained in the frequency domain by applying a two
dimensional Fourier transform to such patterns. In the present work, a ring
fitting method was developed to extract geometrical features out of the dual
rings and to connect these features with several experimental parameters. It was
found that the radius of ring equaled to the wavevector of SPPs. Its orientation
revealed the propagation direction of SPPs. The coordinate distance of the center
of ring gave the parallel component of the wavevector of the incident light,
which was regulated by the incident angle. The ring-broadening factor reflected
the propagation length of SPPs in a reciprocal relationship. Systematical and
quantitative interpretations in the frequency domain not only advanced the basic
understanding on the PSF of SPRM but also opened up the possibility to utilize
these frequency-domain features for detection and sensing purposes in future.
PMID- 29965734
TI - Construction of a Stable Ru-Re Hybrid System Based on Multifunctional MOF-253 for
Efficient Photocatalytic CO2 Reduction.
AB - Using the open N,N'-chelating sites of MOF-253 (Al(OH)(dcbpy), dcbpy = 2,2'
bipyridine-5,5'-dicarboxylic acid) to coordinate with Re(I), a linker anchored Re
complex MOF-253-Re(CO)3Cl active for photocatalytic CO2 reduction was obtained.
Unlike the homogeneous bipyridine containing Re complexes which produce CO during
photocatalytic CO2 reduction, formate was obtained as the main CO2 reduction
product over the as-obtained MOF-253-Re(CO)3Cl. The linker anchored MOF-253
Re(CO)3Cl showed superior photocatalytic performance compared to its homogeneous
counterpart since the usual formation of the bimolecular Re intermediate leading
to the deactivation of the homogeneous Re complex was significantly inhibited in
the MOF supported Re complex. To enhance its light absorption, a linker anchored
Ru sensitizer was simultaneously constructed in MOF-253-Re(CO)3Cl (Ru-MOF-253
Re). The total TON (TON is defined as mole of the evolved H2, CO, and HCOO- over
per amount of Rhenium) for CO2 reduction (28.8 in 4 h) over the as-obtained Ru
MOF-253-Re system is comparable or even superior to most already reported Re
carbonyl complexes featuring bpy ligands and the Ru-Re bimetallic supramolecular
systems constructed via the covalent bond under similar reaction conditions. The
enhanced photocatalytic CO2 reduction over the Ru-MOF-253-Re can be ascribed to
the improved visible light absorption and the existence of an efficient
photoinduced charge transfer from Ru sensitizer to Re catalytic center, as
evidenced from the transient absorption studies. The use of MOF-253 as a
metalloligand and support to assemble the Ru-Re system as well as a mediator to
promote the charge transfer from Ru sensitizer to Re catalytic center resembles
the construction of Ru-Re supramolecular structures using covalent bonds, but is
more facile in preparation and provides more flexibility. This study demonstrates
the possibility of using MOFs with open coordination sites as a platform for the
construction of a stable multifunctional hybrid system for artificial
photosynthesis.
PMID- 29965735
TI - Biochemical and Spectroscopic Characterizations of a Hybrid Light-Harvesting
Reaction Center Core Complex.
AB - The light-harvesting 1 reaction center (LH1-RC) complex from Thermochromatium
tepidum exhibits a largely red-shifted LH1 Q y absorption at 915 nm due to
binding of Ca2+, resulting in an "uphill" energy transfer from LH1 to the
reaction center (RC). In a recent study, we developed a heterologous expression
system (strain TS2) to construct a functional hybrid LH1-RC with LH1 from Tch.
tepidum and the RC from Rhodobacter sphaeroides [Nagashima, K. V. P., et al.
(2017) Proc. Natl. Acad. Sci. U. S. A. 114, 10906]. Here, we present detailed
characterizations of the hybrid LH1-RC from strain TS2. Effects of metal cations
on the phototrophic growth of strain TS2 revealed that Ca2+ is an indispensable
element for its growth, which is also true for Tch. tepidum but not for Rba.
sphaeroides. The thermal stability of the TS2 LH1-RC was strongly dependent on
Ca2+ in a manner similar to that of the native Tch. tepidum, but interactions
between the heterologous LH1 and RC became relatively weaker in strain TS2. A
Fourier transform infrared analysis demonstrated that the Ca2+-binding site of
TS2 LH1 was similar but not identical to that of Tch. tepidum. Steady-state and
time-resolved fluorescence measurements revealed that the uphill energy transfer
rate from LH1 to the RC was related to the energy gap in an order of Rba.
sphaeroides, Tch. tepidum, and strain TS2; however, the quantum yields of LH1
fluorescence did not exhibit such a correlation. On the basis of these findings,
we discuss the roles of Ca2+, interactions between LH1 and the RC from different
species, and the uphill energy transfer mechanisms.
PMID- 29965736
TI - Direct Copper-Catalyzed Three-Component Synthesis of Sulfonamides.
AB - First introduced into medicines in the 1930s, the sulfonamide functional group
continues to be present in a wide range of contemporary pharmaceuticals and
agrochemicals. Despite their popularity in the design of modern bioactive
molecules, the underpinning methods for sulfonamide synthesis are essentially
unchanged since their introduction, and rely on the use of starting materials
with preinstalled sulfur-functionality. Herein we report a direct single-step
synthesis of sulfonamides that combines two of the largest monomer sets available
in discovery chemistry, (hetero)aryl boronic acids and amines, along with sulfur
dioxide, using a Cu(II) catalyst, to deliver a broad range of sulfonamides.
Sulfur dioxide is provided by the surrogate reagent DABSO. The reaction tolerates
broad variation in both coupling partners, including aryl, heteroaryl and alkenyl
boronic acids, as well as cyclic and acyclic alkyl secondary amines, and primary
anilines. We validate the method by showing that a variety of drugs, and drug
fragments, can be incorporated into the process.
PMID- 29965737
TI - Impact of Ohmic Resistance on Measured Electrode Potentials and Maximum Power
Production in Microbial Fuel Cells.
AB - Low solution conductivity is known to adversely impact power generation in
microbial fuel cells (MFCs), but its impact on measured electrode potentials has
often been neglected in the reporting of electrode potentials. While errors in
the working electrode (typically the anode) are usually small, larger errors can
result in reported counter electrode potentials (typically the cathode) due to
large distances between the reference and working electrodes or the use of whole
cell voltages to calculate counter electrode potentials. As shown here,
inaccurate electrode potentials impact conclusions concerning factors limiting
power production in MFCs at higher current densities. To demonstrate how the
electrochemical measurements should be adjusted using the solution conductivity,
electrode potentials were estimated in MFCs with brush anodes placed close to the
cathode (1 cm) or with flat felt anodes placed further from the cathode (3 cm) to
avoid oxygen crossover to the anodes. The errors in the cathode potential for
MFCs with brush anodes reached 94 mV using acetate in a 50 mM phosphate buffer
solution. With a felt anode and acetate, cathode potential errors increased to
394 mV. While brush anode MFCs produced much higher power densities than flat
anode MFCs under these conditions, this better performance was shown primarily to
result from electrode spacing following correction of electrode potentials. Brush
anode potentials corrected for solution conductivity were the same for brushes
set 1 or 3 cm from the cathode, although the range of current produced was
different due to ohmic losses with the larger distance. These results demonstrate
the critical importance of using corrected electrode potentials to understand
factors limiting power production in MFCs.
PMID- 29965738
TI - The Critical E4 State of Nitrogenase Catalysis.
AB - The reaction catalyzed by the nitrogenase enzyme involves breaking the stable
triple bond of the dinitrogen molecule and is consequently considered among the
most challenging reactions in biology. While many aspects regarding its atomic
mechanism remain to be elucidated, a kinetic scheme established by David Lowe and
Roger Thorneley has remained a gold standard for functional studies of the enzyme
for more than 30 years. Recent three-dimensional structures of ligand-bound
states of molybdenum- and vanadium-dependent nitrogenases have revealed the
actual site of substrate binding on the large active site cofactors of this class
of enzymes. The binding mode of an inhibitor and a reaction intermediate further
substantiate a hypothesis by Seefeldt, Hoffman, and Dean that the activation of
N2 is made possible by a reductive elimination of H2 that leaves the cofactor in
a super-reduced state that can bind and reduce the inert N2 molecule. Here we
discuss the immediate implications of the structurally observed mode of binding
of small molecules to the enzyme with respect to the early stages of the
Thorneley-Lowe mechanism of nitrogenase. Four consecutive single-electron
reductions give rise to two bridging hydrides at the cluster surface that can
recombine to eliminate H2 and enable the reduced cluster to bind its substrate in
a bridging mode.
PMID- 29965740
TI - The Economics of Wastewater Treatment Decentralization: A Techno-economic
Evaluation.
AB - The existing wastewater treatment infrastructure has not adequately established
an efficient and sustainable use of energy, water, and nutrients. A proposed
scheme based on source separation and water-efficient use is compared to the
current wastewater management paradigm (one largely based on activated sludge)
using techno-economic terms. This paper explores the economic viability of
adopting more sustainable management alternatives and expands the understanding
of the economics of decentralization and source-separation. The feasibility of
three different potential types of source-separation (with different levels of
decentralization) are compared to the conventional centralized activated sludge
process by using recognized economic assessment methodologies together with
widely accepted modeling tools. The alternatives were evaluated for two common
scenarios: new developments and retrofit due to the aging of existing
infrastructures. The results prove that source-separated alternatives can be
competitive options despite existing drawbacks (only when countable incomes are
included), while the hybrid approach resulted in the least cost-effective
solution. A detailed techno-economic evaluation of the costs of decentralization
provides insight into the current constraints concerning the paradigm shift and
the cost of existing technologic inertia.
PMID- 29965741
TI - Desrisking the Cytotoxicity of a Mitochondriotropic Antioxidant Based on Caffeic
Acid by a PEGylated Strategy.
AB - Mitochondrial oxidative damage is related to diverse pathologies, including
cancer and neurodegenerative diseases. Shielding mitochondria from oxidative
damage with mitochondriotropic antioxidants is by now considered an effective
therapeutic strategy. Despite the success of the approach, some concerns related
with cytotoxicity have been reported. For instance, AntiOxCIN6 is a
mitochondriotropic antioxidant based on caffeic acid (CAF) that is cytotoxic in
hepatocarcinoma (HepG2) cell lines. PEGylation, often used to enhance drug
pharmacologic and pharmaceutical properties, was herein applied to modulate
AntiOxCIN6 toxicity drawbacks. So, a dual-functionalization of polyethylene
glycol (PEG) with TPP+ and CAF as targeting and antioxidant arms, respectively,
was performed by a two-step amidation strategy using ethyl chloroformate and
EDC/NHS as coupling reagents. The data showed that the antioxidant properties
related with CAF moiety were maintained in the CAF-PEG-TPP conjugate (CPTPP) and
that PEGylation process reverted the loss of ability to chelate iron observed
with AntiOxCIN6.. In cellular studies, CPTPP was nontoxic to human HepG2 and
neuronal (SH-SY5Y) cells, while both CAF and AntiOxCIN6 demonstrated harmful
effects in the same cell lines. The lack of cytotoxic events linked to oxidative
stress levels observed with CPTPP suggested that PEGylation process somehow
modulates the putative toxicity related with the presence of a catechol moiety
and/or the TPP+ cation. In addition, the mitochondrial oxygen consumption was not
significantly affected by CPTPP treatment in SH-SY5Y cells when compared with
nontreated cells. CPTPP showed remarkable antioxidant effects in cell-based
assays against several oxidative stress-induced agents (H2O2, t-BHP, and FeNTA).
From the data it can be concluded that PEGylation technology can modulate the
toxicity of mitochondriotropic antioxidants without disturbing the antioxidant
profile of the core antioxidant. PEGylation can be considered a relevant tool to
hasten the difficulties related to the design and development of mitochondrial
nontoxic and operative drug candidates.
PMID- 29965742
TI - Intercommunication of DNA-Based Constitutional Dynamic Networks.
AB - Intercommunication between dynamic chemical networks plays a major role in
cellular transformations. Inspired by nature, we introduce the intercommunication
between two constitutional dynamic networks, CDNs, "S" and "T" composed, each, of
four equilibrated supramolecular constituents AA', AB', BA', and BB', and of CC',
CD', DC', and DD', respectively. Each of the constituents is conjugated to a Mg2+
ion-dependent DNAzyme unit that acts as a reporter element for the concentration
of the respective constituent via the catalyzed cleavage of the
fluorophore/quencher-functionalized substrate associated with the respective
DNAzyme reporter. Also, constituents BB' (in CDN "S") and CC' (in CDN "T")
include Mg2+-ion-dependent DNAzymes acting as activator units for generating
triggering signals between the networks. Subjecting CDNs "S" and "T" to the
catalytically cleavable hairpin trigger Hdd' or Haa', respectively, yields input
strands that intercommunicate the CDNs by affecting the time-dependent re
equilibration of the constituents of the counter CDN without affecting the
dynamic equilibrium of the constituents of the CDN that generates the triggering
strands. Treatment of CDNs "S" and "T" with hairpins Hdd' and Haa' (or Hba'),
respectively, stimulates autonomous positive/positive or positive/negative
feedback to the programmed time-dependent up-regulation or down-regulation of the
equilibrated constituents in the two CDNs.
PMID- 29965743
TI - Thiol Reactivity Analyses To Predict Mammalian Cell Cytotoxicity of Water
Samples.
AB - An in chemico high throughput assay based on N-acetylcysteine was developed and
used in conjunction with previous and new mammalian cell cytotoxicity data. Our
objective was to derive an empirical equation with confidence levels for
mammalian cell cytotoxicity prediction. Modeling data included 16 unique sources
of waters and wastewaters of distinct water qualities to encompass a wide range
of real environmental samples. This approach provides a quick screen to identify
those water and wastewaters that could be prioritized for in depth analytical
biological analyses and toxicity. The resulting model can serve as a preliminary
convenient tool to screen for potential mammalian cell cytotoxicity in organic
extracts of a wide variety of water samples.
PMID- 29965744
TI - Influences of In-Furnace Kaolin Addition on the Formation and Emission
Characteristics of PM2.5 in a 1000 MW Coal-Fired Power Station.
AB - The impacts of in-furnace kaolin addition on the formation and emission
characteristics of PM2.5 from a 1000 MW coal-fired utility boiler equipped with
electrostatic precipitators (ESPs) are investigated for the first time ever in
this contribution. Detailed characterization of the chemical composition,
micromorphology, melting characteristics of the fine PM, total fly ash, and/or
bottom ash samples were carried out using the X-ray fluorescence probe, the field
emission scanning electron microscope coupled with an energy dispersive X-ray
detector, the ash fusion analyzer, and the dust specific resistivity analyzer.
The results showed that the formation of fine PM was reduced when kaolin was
added, and the mass concentrations of the particulate matter with the aerodynamic
diameters of <=0.3 and 2.5 MUm (PM0.3 and PM2.5) were reduced by 55.97% and
5.48%, respectively. As expected, kaolin reacted with the volatile mineral vapors
(e.g., Ca, Na) and inhibited their partitioning into ultrafine PM. It was
interesting to find that the added kaolin modified the ash melting behavior, and
promoted the capture of the ultrafine PM onto the coarse particles. What is more,
the added kaolin reduced the specific resistivity of the fly ash and improved
their capture efficiency in the ESPs. Finally, the above combined effects brought
about the emission reductions of 41.27% and 36.72% for PM0.3 and PM2.5 after the
ESPs. These results provided a direct confirmation on the feasibility of in
furnace kaolin addition on the PM reduction in the realistic combustion
conditions.
PMID- 29965745
TI - Is There a Precipitation Sequence in Municipal Wastewater Induced by
Electrolysis?
AB - Electrochemical wastewater treatment can induce calcium phosphate precipitation
on the cathode surface. This provides a simple yet efficient way for extracting
phosphorus from municipal wastewater without dosing chemicals. However, the
precipitation of amorphous calcium phosphate (ACP) is accompanied by the
precipitation of calcite (CaCO3) and brucite (Mg(OH)2). To increase the content
of ACP in the products, it is essential to understand the precipitation sequence
of ACP, calcite, and brucite in electrochemical wastewater treatment. Given the
fact that calcium phosphate (i.e., hydroxyapatite) has the lowest thermodynamic
solubility product and highest saturation index in the wastewater, it has the
potential to precipitate first. However, this is not observed in electrochemical
phosphate recovery from raw wastewater, which is probably because of the very
high Ca/P molar ratio (7.5) and high bicarbonate concentration in the wastewater
resulting in formation of calcite. In the case of decreased Ca/P molar ratio
(1.77) by spiking external phosphate, most of the removed Ca in the wastewater
was used for ACP formation instead of calcite. The formation of of brucite,
however, was only affected when the current density was decreased or the size of
cathode was changed. Overall, the removal of Ca and Mg is much more affected by
current density than the surface area of cathode, whereas for P removal, the
reverse is true. Because of these dependencies, though there is no definite
precipitation sequence among ACP, calcite, and brucite, it is still possible to
influence the precipitation degree of these species by relatively low current
density and high surface area or by targeting phosphorus-rich wastewaters.
PMID- 29965746
TI - Responding to China's Waste Import Ban through a New, Innovative, Cooperative
Mechanism.
PMID- 29965748
TI - Enhanced Trifluralin Metabolism Can Confer Resistance in Lolium rigidum.
AB - Resistance to the pre-emergence herbicide trifluralin is increasing in Australian
annual ryegrass ( Lolium rigidum) populations. Three L. rigidum populations (R1,
R2, and R3) collected from Australian grain fields were identified with
trifluralin resistance. Both target-site and nontarget-site resistance mechanisms
were investigated. No target-site alpha-tubulin mutations were detected in
populations R1 and R3, while an Arg-243-Lys mutation was found in R2. Compared
with the three trifluralin-susceptible populations, enhanced [14C]-trifluralin
metabolism, quantified by measuring the amount of [14C] label partitioning into
the polar phase of a hexane:methanol system, was identified in all the three
resistant populations. This is the first report of metabolic resistance to
trifluralin. Coevolution of target-site and nontarget-site resistance to
trifluralin is occurring, and metabolic resistance is not rare in L. rigidum
populations in Australia. A method was established for trifluralin metabolic
resistance detection, overcoming the difficulties of quantifying this highly
volatile herbicide by chromatographic methods.
PMID- 29965747
TI - A Radical Clock Probe Uncouples H Atom Abstraction from Thioether Cross-Link
Formation by the Radical S-Adenosyl-l-methionine Enzyme SkfB.
AB - Sporulation killing factor (SKF) is a ribosomally synthesized and post
translationally modified peptide (RiPP) produced by Bacillus. SKF contains a
thioether cross-link between the alpha-carbon at position 40 and the thiol of
Cys32, introduced by a member of the radical S-adenosyl-l-methionine (SAM)
superfamily, SkfB. Radical SAM enzymes employ a 4Fe-4S cluster to bind and
reductively cleave SAM to generate a 5'-deoxyadenosyl radical. SkfB utilizes this
radical intermediate to abstract the alpha-H atom at Met40 to initiate cross
linking. In addition to the cluster that binds SAM, SkfB also has an auxiliary
cluster, the function of which is not known. We demonstrate that a substrate
analogue with a cyclopropylglycine (CPG) moiety replacing the wild-type Met40
side chain forgoes thioether cross-linking for an alternative radical ring
opening of the CPG side chain. The ring opening reaction also takes place with a
catalytically inactive SkfB variant in which the auxiliary Fe-S cluster is
absent. Therefore, the CPG-containing peptide uncouples H atom abstraction from
thioether bond formation, limiting the role of the auxiliary cluster to promoting
thioether cross-link formation. CPG proves to be a valuable tool for uncoupling H
atom abstraction from peptide modification in RiPP maturases and demonstrates
potential to leverage RS enzyme reactivity to create noncanonical amino acids.
PMID- 29965749
TI - Pseudaminic Acid on Exopolysaccharide of Acinetobacter baumannii Plays a Critical
Role in Phage-Assisted Preparation of Glycoconjugate Vaccine with High
Antigenicity.
AB - Pseudaminic acid (Pse) has been known for participating in crucial bacterial
virulence and thus is an attractive target in the development of glycoconjugate
vaccine. Particularly, this therapeutic alternative was suggested to be a
potential solution against antibiotic resistant Acinetobacter baumannii that
poses a serious global health threat. Also, Pse was found to be involved in the
exopolysaccharide (EPS) of mild antibiotic resistant A. baumannii strain 54149 (
Ab-54149) of which specific glycosyl linkage can be depolymerized by phage PhiAB6
tailspike protein (PhiAB6TSP). In this study, we found that the antibodies
induced by Ab-54149 EPS was capable of recognizing a range of EPS of other
clinical A. baumannii strains, and deemed as a great potential material for
vaccination. To efficiently acquire homogeneous EPS-derived oligosaccharide with
significant immunogenic activity for the production of glycoconjugate, we used
the PhiAB6TSP for the fragmentation of Ab-54149 EPS instead of chemical methods.
Moreover, insight into the ligand binding characterization of PhiAB6TSP suggested
the branched Pse on the Ab-54149 EPS served as a recognition site of PhiAB6TSP.
The serum boosted by PhiAB6TSP-digested product and carrier protein CRM197
conjugate complex displayed specific sensitivity toward Ab-54149 EPS with
bacterial killing activity. Strikingly, Pse is an ideal epitope with strong
antigenicity, profiting the application of the probe for pathogen detection and
glyco-based vaccine.
PMID- 29965750
TI - Photochemistry in Confined Environments for Single-Chain Nanoparticle Design.
AB - Emulating nature's protein paradigm, single-chain nanoparticles (SCNP) are an
emerging class of nanomaterials. Synthetic access to SCNPs is limited by ultralow
concentrations, demanding reaction conditions, and complex isolation procedures
after single-chain collapse. Herein, we exploit the visible light
photodimerization of styrylpyrene units as chain folding mechanism. Critically,
their positioning along the polymer chain creates a confined environment,
increasing the photocycloaddition quantum yields dramatically, enabling single
chain folding at unrivaled high concentrations without subsequent purification.
Importantly, the enhanced photoreactivity allows for single-chain folding at
lambda = 445 nm LED-irradiation within minutes as well as via ambient light,
enabling an unprecedented folding system. The herein demonstrated enhancement of
quantum yields by steric confinement serves as a blueprint for all photochemical
ligation systems.
PMID- 29965751
TI - Changes in Lipid Profiles of Dried Clams ( Mactra chinensis Philippi and
Ruditapes philippinarum) during Accelerated Storage and Prediction of Shelf Life.
AB - To predict the shelf life through an Arrhenius model and evaluate the changes in
lipid profiles, two types of dried clams were stored at 50 and 65 degrees C and
collected periodically for analysis. The predicted shelf life values of the two
dried clam samples were 530 +/- 14 and 487 +/- 24 h (24 degrees C), and the
relative errors between the actual and predicted values were 5.7 and 6.8%,
respectively. During accelerated storage, the peroxide value, p-anisidine value,
thiobarbituric acid-reactive substances value, total oxidation value, acid value,
and free fatty acid content all increased, while the levels of triacylglycerol,
phosphatidylcholine, phosphatidylethanolamine, major glycerophospholipid
molecular species, and polyunsaturated fatty acid (PUFA) decreased. Moreover,
content of phospholipid containing PUFA decreased significantly than that of
triacylglycerol containing PUFA. Results indicated that the Arrhenius model was
suitable for the shelf life prediction of dried clams and accelerated storage
caused loss in quality of dried clams in terms of lipids.
PMID- 29965752
TI - Optimization of N-Substituted Oseltamivir Derivatives as Potent Inhibitors of
Group-1 and -2 Influenza A Neuraminidases, Including a Drug-Resistant Variant.
AB - On the basis of our earlier discovery of N1-selective inhibitors, the 150-cavity
of influenza virus neuraminidases (NAs) could be further exploited to yield more
potent oseltamivir derivatives. Among the synthesized compounds, 15b and 15c were
exceptionally active against both group-1 and -2 NAs. Especially for 09N1, N2,
N6, and N9 subtypes, they showed 6.80-12.47 and 1.20-3.94 times greater activity
than oseltamivir carboxylate (OSC). They also showed greater inhibitory activity
than OSC toward H274Y and E119V variant. In cellular assays, they exhibited
greater potency than OSC toward H5N1, H5N2, H5N6, and H5N8 viruses. 15b
demonstrated high metabolic stability, low cytotoxicity in vitro, and low acute
toxicity in mice. Computational modeling and molecular dynamics studies provided
insights into the role of R group of 15b in improving potency toward group-1 and
2 NAs. We believe the successful exploitation of the 150-cavity of NAs represents
an important breakthrough in the development of more potent anti-influenza
agents.
PMID- 29965753
TI - Optimization of the Linear-Scaling Local Natural Orbital CCSD(T) Method: Improved
Algorithm and Benchmark Applications.
AB - An optimized implementation of the local natural orbital (LNO) coupled-cluster
(CC) with single-, double-, and perturbative triple excitations [LNO-CCSD(T)]
method is presented. The integral-direct, in-core, highly efficient domain
construction technique of our local second-order Moller-Plesset (LMP2) scheme is
extended to the CC level. The resulting scheme, which is also suitable for
general-order LNO-CC calculations, inherits the beneficial properties of the LMP2
approach, such as the asymptotically linear-scaling operation count, the
asymptotically constant data storage requirement, and the completely independent
domain calculations. In addition to integrating our recent redundancy-free LMP2
and Laplace-transformed (T) algorithms with the LNO-CCSD(T) code, the memory
demand, the domain and LNO construction, the auxiliary basis compression, and the
previously rate-determining two-external integral transformation have been
significantly improved. The accuracy of all of the approximations is carefully
examined on medium-sized to large systems to determine reasonably tight default
truncation thresholds. Our benchmark calculations, performed on molecules of up
to 63 atoms, show that the optimized method with the default settings provides
average correlation and reaction energy errors of less than 0.07% and 0.34
kcal/mol, respectively, compared to the canonical CCSD(T) reference. The
efficiency of the present LNO-CCSD(T) implementation is demonstrated on
realistic, three-dimensional examples. Using the new code, an LNO-CCSD(T)
correlation energy calculation with a triple-zeta basis set is feasible on a
single processor for a protein molecule including 2380 atoms and more than 44000
atomic orbitals.
PMID- 29965754
TI - Construction of Fermi Potentials from Electronic Wave Functions.
AB - The Fermi potential, vF(r), is the nonclassical part of the multiplicative
effective potential appearing in the one-particle Schrodinger-type equation for
the square root of the electron density. The usual way of constructing vF(r) by
inverting that equation produces unsatisfactory results when applied to electron
densities expanded in Gaussian basis sets. We suggest a different method that is
based on an explicit formula for vF(r) in terms of the interacting one- and two
electron reduced density matrices of the system. This method is exact in the
basis-set limit and yields accurate approximations to the basis-set-limit vF(r)
when applied to reduced density matrices represented in terms of finite basis
sets. Illustrative applications involve atomic and molecular wave functions
generated at various levels of ab initio theory. It is also shown how to
construct the Pauli and exchange-correlation potentials of any system starting
with only vF(r).
PMID- 29965755
TI - Activation Dynamics of the Neurotensin G Protein-Coupled Receptor 1.
AB - A replica-exchange protocol remarkably enhances the sampling of the activation
dynamics of the neurotensin receptor type 1, a G protein-coupled receptor (GPCR)
and important drug target. Our work highlights the dynamic communication between
conformational changes of the agonist and the G protein-binding site, via
contraction-oscillation of the orthosteric pocket. It also gives insights into
the mechanism by which certain mutations diminish or stimulate activation. The
replica-exchange protocol effectively enhances barrier crossing where standard
brute-force molecular dynamics simulations fail. It is readily applicable to
other GPCRs and represents a promising approach for virtual ligand screening,
using the typical features of receptor activation as a benchmark.
PMID- 29965756
TI - Predicting Pathways between Distant Configurations for Biomolecules.
AB - Many of the most interesting rearrangements associated with function and
dysfunction of biomolecules involve complex, highly nonlinear pathways.
Predicting these convoluted changes in structure is an important research
challenge, since knowledge of key intermediate conformations at an atomic level
of detail has the potential to inform the design of novel therapeutic strategies
with enhanced specificity. The identification of kinetically relevant pathways
can be strongly dependent on the construction of a physically relevant initial
pathway between specified end points, avoiding artifacts such as chain crossings.
In this contribution we describe an enhanced interpolation procedure to
characterize initial pathways for complex rearrangements of a histone tail, alpha
helix to beta-sheet conversion for amyloid-beta17-42, and EGFR kinase activation.
Complete connected initial pathways with relatively low overall barriers are
obtained in each case using an enhanced quasi-continuous interpolation scheme.
This approach will help to extend the complexity and time scales accessible to
computer simulation.
PMID- 29965757
TI - A Light-Releasable Potentially Prebiotic Nucleotide Activating Agent.
AB - Investigations into the chemical origin of life have recently benefitted from a
holistic approach in which possible atmospheric, organic, and inorganic systems
chemistries are taken into consideration. In this way, we now report that a
selective phosphate activating agent, namely methyl isocyanide, could plausibly
have been produced from simple prebiotic feedstocks. We show that methyl
isocyanide drives the conversion of nucleoside monophosphates to
phosphorimidazolides under potentially prebiotic conditions and in excellent
yields for the first time. Importantly, this chemistry allows for repeated
reactivation cycles, a property long sought in nonenzymatic oligomerization
studies. Further, as the isocyanide is released upon irradiation, the possibility
of spatially and temporally controlled activation chemistry is thus raised.
PMID- 29965758
TI - Pectin Conformation in Solution.
AB - The interplay of degree of methylesterification (DM), pH, temperature, and
concentration on the macromolecular interactions of pectin in solution has been
explored. Small-angle X-ray scattering complemented by atomic force microscopy
and molecular dynamics was employed to probe chain dimensions and solution
structure. Two length scales have been observed with the first level of structure
characterising chain clusters with sizes ranging between 100-200 nm. The second
level of structure arises from single biopolymer chains with a radius of gyration
between ~6 and 42 nm. The development of a range of macromolecular dimensions in
vitro and in silico shows that the chain flexibility increases with DM and at
acidic pH, whereas hydrogen bonding is the responsible thermodynamic driving
force for cluster formation. High methyl pectins create structures of lower
fractal dimension with less efficient packing. This work unveils pectin
conformations covering most of its industrially and biologically relevant
environments, enabling rational design of advanced biomaterials based on pectin.
PMID- 29965759
TI - 2,4-Diaminoquinazolines as Dual Toll-like Receptor (TLR) 7/8 Modulators for the
Treatment of Hepatitis B Virus.
AB - A novel series of 2,4-diaminoquinazolines was identified as potent dual Toll-like
receptor (TLR) 7 and 8 agonists with reduced off-target activity. The
stereochemistry of the amino alcohol was found to influence the TLR7/8
selectivity with the ( R) isomer resulting in selective TLR8 agonism. Lead
optimization toward a dual agonist afforded ( S)-3-((2-amino-8-fluoroquinazolin-4
yl)amino)hexanol 31 as a potent analog, being structurally different from
previously described dual agonists ( McGowan J. Med. Chem. 2016 , 59 , 7936 ).
Pharmacokinetic and pharmacodynamic (PK/PD) studies revealed the desired high
first pass profile aimed at limiting systemic cytokine activation. In vivo
pharmacodynamic studies with lead compound 31 demonstrated production of
cytokines consistent with TLR7/8 activation in mice and cynomolgus monkeys and ex
vivo inhibition of hepatitis B virus (HBV).
PMID- 29965760
TI - New Sweet-Tasting C21 Pregnane Glycosides from the Roots of Myriopteron extensum.
AB - To investigate the sweet-tasting components in the roots of Myriopteron extensum,
the phytochemical study of its roots was conducted, which led to the discovery of
12 new C21 pregnane glycosides (extensumside M-X, 1-12) and two known ones
(extensumside C and extensumside E, 13-14). Their chemical structure elucidation
was accomplished by means of spectroscopic methods: IR, UV, ESI-MS, and NMR (1H
NMR, 13C NMR, HSQC, 1H-1H COSY, HMBC, HSQC-TOCSY, and ROESY), as well as the
chemical evidence. Sensory analysis of these compounds revealed that nine of them
(1, 3, 4, 5, 6, 7, 8, 13, and 14) are highly sweet-tasting compounds. Their
sweetness intensities are 25 to 400 times greater than that of sucrose. Analysis
of the structure-activity relationship (SAR) indicated that the sweet intensities
of the isolated compounds are closely related to the aglycone 3beta,16alpha
dihydroxy-pregn-5-en-20-one, the number and type of the monosaccharide in the
sugar chain linked to C-3 and C-16 and the position of the mBe group.
PMID- 29965761
TI - Interactions of Long-Chain Perfluorotelomer Alcohol and Perfluorinated
Hydrocarbons with Model Decomposer Membranes.
AB - Perfluorinated hydrocarbons and their polar derivatives are produced annually in
high quantities and find multiple industrial and technological applications due
to their chemical and physical durability, significant hydro- and lipophobicity
and excellent surface activity. Unfortunately, multiple perfluorinated compounds
are recognized as persistent organic pollutants as they are completely
nonbiodegradable and accumulate in soils and sediments. In our studies, we
applied Langmuir monolayers formed by different structural phospholipids as
models of soil bacteria and fungi membranes and investigated the effects exerted
by long-chain perfluorinated pollutants, perfluorotelomer alcohol and two
structurally different perfluorinated hydrocarbons, on the artificial membranes.
Various mutually complemental methods such as surface pressure-mean molecular
area isotherm registration, Brewster angle microscopy (BAM), and grazing
incidence X-ray diffraction (GIXD) were applied. It turned out that the presence
of the perfluorinated chemicals profoundly affected the phospholipid monolayers.
The miscibility of the phospholipid with the perfluorotelomer alcohol depended
strongly on the size and charge of the polar headgroup. Additionally, it was
observed by BAM that the presence of the perfluorinated molecules significantly
changed the texture of all the investigated phospholipid monolayers. On the basis
of the BAM and GIXD results and other studies described in the scientific
literature, we postulated that the perfluorinated hydrocarbons form an additional
monolayer anchored on top of the phospholipid film. Our studies prove that both
polar and nonpolar perfluorinated pollutants can be toxic to decomposer organisms
and that their toxicity is strictly correlated with the phospholipid composition
of the cellular membrane.
PMID- 29965762
TI - Benchmarking of the R-7 Anisotropic Dispersion Energy Term on the S22 Dimer Test
Set.
AB - The effects of including the anisotropic E7 term to the dispersion energy in
addition to the leading E6 term are examined by using the effective fragment
potential (EFP) method on the S22 test set. In this study, the full anisotropic
E7 term is computed whereas the isotropic and spherical approximations are used
for the E6 term. It is found that the E7 term is positive for hydrogen-bonded
complexes and has a magnitude that can be as large as 50% of E6, giving rise to
larger intermolecular distances than those obtained with E6 alone. The large
positive value of E7 is analyzed for the hydrogen-bonded uracil dimer; it is
found to originate from the large magnitude of the dynamic polarizability tensors
as well as the proximity of the LMOs involved in hydrogen bonding. Conversely, E7
tends to be negative for dispersion-dominant complexes, and it has a very small
magnitude for such complexes. The optimized geometries for these systems are
therefore not greatly affected by the presence of the E7 term. For the mixed
systems in the S22 test set, an intermediate behavior is observed. Overall, the
E7 term is most important for systems with hydrogen bonding interactions and
mixed systems. A full anisotropic treatment of the E6 term and higher order terms
may need to be included to obtain more accurate interaction energies and
geometries.
PMID- 29965763
TI - Insights into Excited State Intramolecular Proton Transfer: An Alternative Model
for Excited State Proton Transfer of Green Fluorescence Protein.
AB - The excited state intramolecular proton transfer (ESIPT) that occurs in the o
sulfonamide analogue ( o-TsABDI) of the green fluorescent protein (GFP)
chromophore provides an alternative model to get insights into the excited state
proton transfer (ESPT) related photophysics of GFP. In this article, we explored
the ESIPT-related photophysics of o-TsABDI by electronic absorption and
fluorescence emission spectra in a wide polarity range of solvents, cis- trans
photoisomerization experiment, and Coulomb-attenuating method (CAM)/time
dependent (TD) density functional theory (DFT) calculations. We found that the
whole ESIPT process involves four steps. The first step is photoexcitation of o
TsABDI, which does not involve charge transfer (CT). The second step is ESIPT and
accompanying electron transfer from the n orbital of the sulfonamide nitrogen to
the half-filled pi orbital of the 4-benzylideneimidazolone moiety. The third step
is fluorescence emission of the zwitterionic o-TsABDI and accompanying CT from
the pi* orbital of the 4-benzylideneimidazolone moiety to the half-filled n
orbital of the sulfonamide nitrogen. The last step involves irreversible and
barrierless proton recombination. In contrast to the isolated GFP chromophore and
its p- and m-amino analogues, the S1 excited state of o-TsABDI does not relax by
way of cis- trans photoisomerization through the S1/S0 conical intersection CI(I)
by rotating around the I-bond, but follows the ESIPT pathway. The low
fluorescence quantum yield of the zwitterionic o-TsABDI might be due to (1) the
fluorescence that involves the low-probability pi* -> n charge transfer and (2)
nonradiative relaxation through the S1/S0 conical intersection CI(P") by rotating
around the P-bond.
PMID- 29965764
TI - Phase Diagram of Methane Hydrates and Discovery of MH-VI Hydrate.
AB - Methane hydrate is not only the predominant natural deposits of permafrost and
continental margins of Earth but also the dominant methane-containing phase in
the nebula and major moons of gas giants. Depending on the surrounding
environment (mainly pressure), seven methane hydrate phases have been discovered
by experiment or predicted by computer simulation, such as clathrate methane
hydrates I, II, H, and K, and filled-ice methane hydrates III, IV, and V. Using
extensive Monte Carlo packing algorithm and density functional theory
optimization, here we predict a partial clathrate methane hydrate VI built by
basic units of 4262 water bowl encapsulating a methane molecule, which is
dynamically stable from the computed phonon dispersion. Its density and
structural characteristics are comparable to that of filled-ice methane hydrate
III. By calculating the formation enthalpies of a variety of candidate phases at
different pressures, a phase diagram of methane hydrates is constructed. As
pressure rises, phase transitions occur among the methane hydrates along with
decreasing water/methane molecular ratios. The newly predicted methane hydrate VI
emerges as the most stable phase in the region between clathrate phase II and
filled-ice phase III, suggesting that methane hydrate VI might be synthesized in
a laboratory under accessible conditions.
PMID- 29965765
TI - Trehalose in Water Revisited.
AB - Trehalose, commonly found in living organisms, is believed to help them survive
severe environmental conditions, such as drought or extreme temperatures. With
the aim of trying to understand these properties, two recent neutron scattering
studies investigate the structure of trehalose water solutions but come to
seemingly opposite conclusions. In the first study, which looks at two
concentrations of trehalose-water mole ratios of 1:100 and 1:25, the conclusion
is that trehalose hydrogen-bonds to water rather weakly and has a relatively
minor impact on the structure of water in solution compared to bulk water. On the
other hand, for the other, using a mole ratio of 1:38, the conclusion is that the
water structure is rather substantially modified by the presence of trehalose and
that the hydrogen bonding between water and trehalose hydroxyl groups is
significant. In an attempt to try to understand the origin of these divergent
views, which arise from similar but independent analyses of different neutron
diffraction data, we have performed additional X-ray scattering experiments,
which are highly sensitive to water structure, at the same trehalose-water
concentrations used in the first study, and combined these with empirical
potential structure refinement on the previously collected neutron data. The new
analysis unequivocally confirms that trehalose does indeed have only a minor
impact on the structure of water, at all three concentrations, and forms
relatively weak hydrogen bonds with water. Far from being discrepant with the
existing literature, our new analysis of the different datasets suggests a
natural explanation for the increased glass-transition temperature of trehalose
compared to other sugars and hence its enhanced effectiveness as a protectant
against drought stress.
PMID- 29965766
TI - Boron Teetotum: Metallic [Ti(B6C xN y)] q and Bimetallic [Ti2(B6C xN y)] q Nine
Membered Heterocycles with x + y = 3 and -1 <= q <= 3.
AB - We investigated the geometry, stability, and aromaticity of a series of singly
and doubly titanium-doped boron clusters. Ti dopants bring in planar cyclic form
with a nine-membered boron ring B9- and B93- and C and N isoelectronic
derivatives where perfectly planar B6N3, B6CN2, B6C2N, and B6C3 heterorings are
coordinated with one and two Ti atoms. The presence of both C and N atoms induces
bimetallic heterocycles while Ti2B9q clusters are not stable in cyclic form.
Doubly Ti doped clusters have the shape of a teetotum toy. High thermodynamic
stability of these bimetallic boron heterocycles, that are global equilibrium
structures of corresponding systems, can be understood as the result of a
stabilizing overlap between bonding and antibonding MOs of Ti2 with different
eigenstates of B6C xN y cycles. Both C and N elements, which are more
electronegative than the B atom, also enjoy the formation of planar nine-membered
ring via classical 2c-2e bonding, rather than occupancy of high coordination
position. A double aromaticity feature which comprises both sigma and pi
aromaticity is supported by magnetic responses of electron density within a
planar cycle. Such an aromatic character is also in line with the classical
electron count for both sets of delocalized sigma and pi electron systems.
PMID- 29965767
TI - Quantitatively Adequate Calculations of the H-Chelate Ring Distortion upon the S0
-> S1(pipi*) Excitation in Internally H-Bonded o-Anthranilic Acid: CC2 Coupled
Cluster versus TDDFT.
AB - The S0 -> S1(pi -> pi*) excitation in o-aminobenzoic acid causes strengthening of
the N-H...O intramolecular hydrogen bond. The interplay of the hydrogen bond
shortening, the hydrogen atom dislocation along the hydrogen bond, and the
skeletal relaxation is investigated. These effects often cause the appearance of
dual fluorescence from the pi-conjugated internally H-bonded molecules, which is
traditionally interpreted as the evidence of the excited-state intramolecular
proton transfer process: ESPIT. Hence, their quantitative modeling is an
important but demanding task for computational photochemistry. Extensive
calculations using CC2 method (the perturbative approximation to CCSD coupled
cluster) and TDDFT(B3LYP) were performed with the series of (aug)-cc-pVXZ(X =
D,T,Q) basis sets. CC2 predicts remarkable shortening of the O...H distance by
0.273 A accompanied by the skeleton relaxation that involves considerable
distortions of valence angles of the amino group (up to 7.3 degrees ) and within
the benzene ring (up to 5 degrees ). Additionally, moderate changes (<0.046 A) of
the bond alternation in the pi-electronic system and the hydrogen atom
dislocation along the hydrogen bond (0.043 A) are predicted. The CC2 method
yields 90% of the magnitude of the experimentally based geometry changes,
estimated in the earlier studies via Franck-Condon fit to the LIF spectra, while
the TDDFT results approach only 65% of the experimental values.
PMID- 29965768
TI - Phonon Spectrometric Evaluation of the Solute-Solvent Interface in Solutions of
Glycine and Its N-Methylated Derivatives.
AB - From the perspective of O:H-O bond cooperativity, we analyzed the solute
capability of transiting the O:H-O bond from the mode of ordinary water to the
hydration state and its consequence on the solution viscosity and surface stress.
Phonon spectrometric results suggest that glycine and its N-methyl derivatives
strongly affect the surrounding solvent molecules through H <-> H repulsion and
dipolar polarization. The H <-> H interproton repulsion disrupts the surface
stress, and the polarization enhances the solution viscosity.
PMID- 29965769
TI - Modification of the Potential Landscape of Molecular Rotors on Au(111) by the
Presence of an STM Tip.
AB - Molecular rotors on solid surfaces are fundamental components of molecular
machines. No matter whether the rotation is activated by heat, electric field or
light, it is determined by the intrinsic rotational potential landscape.
Therefore, tuning the potential landscape is of great importance for future
applications of controlled molecular rotors. Here, using scanning tunneling
microscopy (STM), we demonstrate that both tip-molecule distance and sample bias
can modify the rotational potential of molecular rotors. We achieve the potential
energy difference variations of ~0.3 meV/pm and ~18 meV/V between two
configurations of a molecular rotor, a tetra- tert-butyl nickel phthalocyanine
molecule on Au(111) substrate. Further analysis indicates that the mechanism of
modifying the rotational potential is a combination of the van der Waals
interaction and the interaction between the molecular dipole and an electric
field. This work provides insight into the methods used to modify the effective
rotational potential energy of molecular rotors.
PMID- 29965770
TI - QM/MM Molecular Dynamics Investigations of the Substrate Binding of Leucotriene
A4 Hydrolase: Implication for the Catalytic Mechanism.
AB - LTA4H is a monozinc bifunctional enzyme which exhibits both aminopeptidase and
epoxide hydrolase activities. Its dual functions in anti- and pro-inflammatory
roles have attracted wide attention to the inhibitor design. In this work, we
tried to construct Michaelis complexes of LTA4H with both a native peptide
substrate and LTA4 molecule using combined quantum mechanics and molecular
mechanics molecular dynamics simulations. First of all, the zinc ion is
coordinated by H295, H299, and E318. For its aminopeptidase activity, similar to
conventional peptidases, the fourth ligand to the zinc ion is suggested to be an
active site water, which is further hydrogen bonded with a downstream glutamic
acid, E296. For the epoxide hydrolase activity, the fourth ligand to the zinc ion
is found to be an epoxy oxygen atom. The potential of mean force calculation
indicates about an 8.5 kcal/mol activation barrier height for the ring-opening
reaction, which will generate a metastable carbenium intermediate. Subsequent
frontier molecular orbital analyses suggest that the next step would be the
nucleophilic attacking reaction at the C12 atom by a water molecule activated by
D375. Our simulations also analyzed functions of several important residues like
R563, K565, E271, Y383, and Y378 in the binding of peptide and LTA4.
PMID- 29965771
TI - Kinetic Study of Ligand Binding and Conformational Changes in Inducible Nitric
Oxide Synthase.
AB - Nitric oxide synthases (NOSs) are heme enzymes that generate highly reactive
nitric oxide from l-arginine (l-Arg) in a complex mechanism that is still only
partially understood. We have studied carbon monoxide (CO) binding to the
oxygenase domain of murine inducible NOS (iNOS) by using flash photolysis. The
P420 and P450 forms of the enzyme, assigned to a protonated and unprotonated
proximal cysteine, through which the heme is anchored to the protein, show
markedly different CO rebinding properties. The data suggest that P420 has a
widely open distal pocket that admits water. CO rebinding to the P450 form
strongly depends on the presence of the substrate l-Arg, the intermediate Nomega
hydroxy-l-arginine, and the cofactor tetrahydrobiopterin. After adding these
small molecules to the enzyme solution, the CO kinetics change slowly over the
hours. This process can be described as a relaxation from a fast rebinding,
metastable species to a slowly rebinding, thermodynamically stable species, which
we associate with the enzymatically active form. Our results allow us to
determine kinetic parameters of l-Arg binding to the ferrous deoxy iNOS protein
for the first time and also provide clues regarding the nature of structural
differences between the two interconverting species.
PMID- 29965772
TI - Stress Dissipation in Cucurbit[8]uril Ternary Complex Small Molecule Adhesives.
AB - The ability to control supramolecular and macroscopic self-assembly and
disassembly holds great potential for responsive, reversible adhesives that can
efficiently broker stresses accumulated between two surfaces. Here,
cucurbit[8]uril is used to directly adhere two functionalized mica substrates
creating surface-surface interactions that are held together through
photoreversible CB[8] heteroternary complexes. Comparison of single-molecule,
bulk, and macroscopic adhesion behavior give insight into cooperativity and
stress dissipation in dynamic adhesive systems.
PMID- 29965773
TI - Reactivity of Arynes for Arene Dearomatization.
AB - An unprecedented aryne-mediated dearomatization reaction is described. An aryne
intermediate generated from arenesulfonyl ynamide-tethered triynes and tetraynes
reacts with both the pi-systems of a tethered alkene and the arenesulfonyl group
to generate cyclohexa-1,3-diene-containing pentacyclic and hexacyclic frameworks.
Density functional theory (DFT) calculations show a nucleophilic dearomatization
mechanism involving a zwitterionic intermediate derived from an aryne. A novel
halogen effect on the efficiency of the dearomatization and deterrence of
aromatization of the cyclohexa-1,3-diene moiety was also observed.
PMID- 29965774
TI - Disorder at the Tips of a Disease-Relevant Abeta42 Amyloid Fibril: A Molecular
Dynamics Study.
AB - We present a simulation study of the early events of peptide dissociation from a
fibril of the Alzheimer's Abeta42 peptide. The fibril consists of layers of two
adjacent Abeta42 peptides each folded in an S-shaped structure which has been
determined by solid state NMR spectroscopy of a monomorphic disease-relevant
species. Multiple molecular dynamics runs (16 at 310 K and 15 at 370 K) were
carried out starting from an 18-peptide protofibril for a cumulative sampling of
about 15 MUs. The simulations show structural stability of the fibrillar core and
an overall increase in the twist to about 3 degrees. The N-terminal segment 1-14
is disordered in all peptides. At both ends of the fibril, the central segment 21
29, which includes part of the beta2 strand, dissociates in some of the
simulations. The beta1 and beta3 strands, residues 15-20 and 35-41, respectively,
are structurally stable. The transient binding of the N-terminal stretch to the
beta3 strand of the adjacent peptide at the tip is likely to contribute to the
arrest phase of the stop-and-go mechanism.
PMID- 29965775
TI - Unveiling Noncovalent Interactions in Imidazolium, Pyrrolidinium, or Quaternary
Ammonium Cation and Acetate Anion Based Protic Ionic Liquids: Structure and
Spectral Characteristics.
AB - In the present work protic ionic liquids (PILs) composed of imidazolium-,
quaternary ammonium-, or pyrrolidinium-dications and acetate (OAc-) anion have
been modeled as the dication-anion complexes through the M06-2x based density
functional theory. It has been shown that cation-anion interaction energies are
larger for the PILs containing the quaternary ammonium cation, which can be
attributed to strong hydrogen bonding from the terminal ammonium protons.
Underlying N-H...O and C-H...O hydrogen bonding, electrostatic, and van der Waals
interactions are unraveled using the natural bond orbital analyses in conjunction
with the quantum theory of atoms in molecules (QTAIM) and noncovalent interaction
index reduced density gradient methods. The ramifications of noncovalent binding
to 1H NMR and vibrational spectra are presented. The calculations further
demonstrate a linear correlation of the kinetic energy density parameter G( r) in
QTAIM analysis with the characteristic frequency shift of -NH3+ stretching in the
dication-anion complexes. Moreover, the chemical shifts (deltaH) in 1H NMR
spectra from theory reveal larger deshielding; the corresponding deltaH value
correlates well with proton affinities and cation-anion binding energies as well.
Effect of solvent (DMSO) on structure, binding energies, and 1H NMR are
presented. The shifts of the characteristic carbonyl and the terminal ammonium
stretching vibrations accompanying the dication-anion complexes from gas phase
calculations are in consonance with the self-consistent reaction field theory.
PMID- 29965776
TI - Dynamic Nature of CTCF Tandem 11 Zinc Fingers in Multivalent Recognition of DNA
As Revealed by NMR Spectroscopy.
AB - The 11 zinc fingers (ZFs) of the transcription factor CTCF play a versatile role
in the regulation of gene expression. CTCF binds to numerous genomic sites to
form chromatin loops and topologically associated domains and thus mediates the
3D architecture of chromatin. Although CTCF inter-ZF plasticity is essential for
the recognition of multiple genomic sites, the dynamic nature of its 11 ZFs
remains unknown. We assigned the chemical shifts of the CTCF ZFs 1-11 and solved
the solution structures of each ZF. NMR backbone dynamics, residual dipolar
couplings, and small-angle X-ray scattering experiments suggest a high inter-ZF
plasticity of the free-form ZFs 1-11. As exemplified by two different
protocadherin DNA sequences, the titration of DNAs to 15N-labeled CTCF ZFs 1-11
enabled systematic mapping of binding of CTCF ZFs to various chromatin sites. Our
work paves the way for illustrating the molecular basis of the versatile DNA
recognized by CTCF and has interesting implications for its conformational
transition during DNA binding.
PMID- 29965777
TI - Spring-Like Pseudoelectroelasticity of Monocrystalline Cu2S Nanowire.
AB - Prediction from the dual-phase nature of superionic conductors-both solid and
liquid-like-is that mobile ions in the material may experience reversible
extraction-reinsertion by an external electric field. However, this type of
pseudoelectroelasticity has not been confirmed in situ, and no details on the
microscopic mechanism are known. Here, we in situ monitor the
pseudoelectroelasticity of monocrystalline Cu2S nanowires (NWs) using
transmission electron microscopy (TEM). Specifically, we reveal the atomic scale
details including phase transformation, migration and redox reactions of Cu+
ions, nucleation, growth, as well as spontaneous shrinking of Cu protrusion.
Caterpillar-diffusion-dominated deformation is confirmed by the high-resolution
transmission electron microscopy (HRTEM) observation and ab initio calculation,
which can be driven by either an external electric field or chemical potential
difference. The observed spring-like behavior was creatively adopted for electric
nanoactuators. Our findings are crucial to elucidate the mechanism of
pseudoelectroelasticity and could potentially stimulate in-depth research into
electrochemical and nanoelectromechanical systems.
PMID- 29965778
TI - Application of metabolomics to preeclampsia diagnosis.
AB - : Preeclampsia is a multifactorial disorder defined by hypertension and increased
urinary protein excretion during pregnancy. It is a significant cause of maternal
and neonatal deaths worldwide. Despite various research efforts to clarify
pathogenies of preeclampsia and predict this disease before beginning of
symptoms, the pathogenesis of preeclampsia is unclear. Early prediction and
diagnosis of women at risk of preeclampsia has not markedly improved. Therefore,
the objective of this study was to perform a review on metabolomic articles
assessing predictive and diagnostic biomarkers of preeclampsia. Four electronic
databases including PubMed/Medline, Web of Science, Sciencedirect, and Scopus
were searched to identify studies of preeclampsia in humans using metabolomics
from inception to March 2018. Twenty-one articles in a variety of biological
specimens and analytical platforms were included in the present review.
Metabolite profiles may assist in the diagnosis of preeclampsia and
discrimination of its subtypes. Lipids and their related metabolites were the
most generally detected metabolites. Although metabolomic biomarkers of
preeclampsia are not routinely used, this review suggests that metabolomics has
the potential to be developed into a clinical tool for preeclampsia diagnosis and
could contribute to an improved understanding of disease mechanisms.
ABBREVIATIONS: PE: preeclampsia; sFlt-1: soluble FMS-like tyrosine kinase-1;
PlGF: placental growth factor; GC-MS: gas chromatography-mass spectrometry; LC
MS: liquid chromatography-mass spectrometry; NMR: nuclear magnetic resonance
spectroscopy; HMDB: human metabolome database; RCT: randomized control trial; e
PE: early-onset PE; l-PE: late-onset PE; PLS-DA: partial least-squares
discriminant analysis; CRL: crown-rump length; UtPI: uterine artery Doppler
pulsatility index; BMI: body mass index; MAP: mean arterial pressure; OS:
oxidative stress; PAPPA: plasma protein A; FTIR: Fourier transform infrared;
BCAA: branched chain amino acids; Arg: arginine; NO: nitric oxide.
PMID- 29965779
TI - Satisfaction with access and quality of healthcare services for people with
spinal cord injury living in the community.
AB - OBJECTIVE: To identify barriers to access healthcare services and reveal
determinants of satisfaction with healthcare services in people with chronic
spinal cord injury (SCI). DESIGN: Cross-sectional survey. SETTING: Community
setting in Switzerland. PARTICIPANTS: People with chronic SCI. INTERVENTIONS: Non
applicable. OUTCOME MEASURES: Questionnaire-based evaluation of availability and
quality of healthcare services for secondary health conditions, satisfaction with
fulfillment of healthcare needs, and preference for care from a hypothetical
service provider with limited specialized SCI care expertise but in close
proximity over comprehensive care from an existing specialized SCI center located
at a greater distance. RESULTS: Close to three-quarter of participants (70%)
indicated satisfaction with healthcare services received for SCI related health
conditions. Elderly individuals (61+ years old) rated the availability and
quality of healthcare 6% to 11% higher than younger individuals. The perceived
fulfillment of healthcare needs was lower in people with incomplete paraplegia
(odds ratio (OR) 2.11, 95%-credibility interval (CI) 1.18-3.84), chronic pain (OR
1.85, CI 1.12-3.08), insufficient access to long distance transportation (OR
5.81, CI 2.74-12.82), and longer travel distances to specialized SCI centers.
CONCLUSION: Perceived inadequateness of access to healthcare services was partly
related to transportation barriers, suggesting that outreach services or support
with transportation are possible solutions. People with incomplete paralysis and
pain consistently rated the fulfillment of care needs associated with SCI less
favorably, pointing to the need for enhanced advocacy for this vulnerable groups.
PMID- 29965780
TI - Salmonella enterica Contamination of Market Fresh Tomatoes: A Review.
AB - Salmonella contamination associated with market fresh tomatoes has been
problematic for the industry and consumers. A number of outbreaks have occurred,
and dollar losses for the industry, including indirect collateral impact to
agriculturally connected communities, have run into the hundreds of millions of
dollars. This review covers these issues and an array of problems and potential
solutions surrounding Salmonella contamination in tomatoes. Some other areas
discussed include (i) the use of case-control studies and DNA fingerprinting to
identify sources of contamination, (ii) the predilection for contamination based
on Salmonella serovar and tomato cultivar, (iii) internalization, survival, and
growth of Salmonella in or on tomatoes and the tomato plant, in biofilms, and in
niches ancillary to tomato production and processing, (iv) the prevalence of
Salmonella in tomatoes, especially in endogenous regions, and potential sources
of contamination, and (v) effective and experimental means of decontaminating
Salmonella from the surface and stem scar regions of the tomato. Future research
should be directed in many of the areas discussed in this review, including
determining and eliminating sources of contamination and targeting regions of the
country where Salmonella is endemic and contamination is most likely to occur.
Agriculturalists, horticulturalists, microbiologists, and epidemiologists may
make the largest impact by working together to solve other unanswered questions
regarding tomatoes and Salmonella contamination.
PMID- 29965782
TI - Deep sequencing of BCR-ABL1 kinase domain mutations in chronic myeloid leukemia
patients with resistance to tyrosine kinase inhibitors.
AB - Tyrosine kinase inhibitor (TKI) therapy is the current treatment of choice for
patients with chronic phase chronic myeloid leukemia (CML) leading to rapid and
durable hematological as well as molecular responses. However, emergence of
resistance to TKIs has been the major obstacle to treatment success on long term.
In this regard kinase domain mutations are the most common mechanism of therapy
failure. In this study, we analyzed peripheral blood samples from 17 CML patients
who had developed resistance to various TKIs by using next-generation sequencing
parallel to Sanger sequencing. BCR-ABL1 kinase domain mutations have been found
in 59% of the cohort. Our results demonstrate that next-generation sequencing
results in a higher mutational detection rate than reported with conventional
sequencing methodology. Furthermore, it showed the clonal diversity more
accurately.
PMID- 29965781
TI - RAB26-dependent autophagy protects adherens junctional integrity in acute lung
injury.
AB - : Microvascular barrier dysfunction is the central pathophysiological feature of
acute lung injury (ALI). RAB26 is a newly identified small GTPase involved in the
regulation of endothelial cell (EC) permeability. However, the mechanism behind
this protection has not been clearly elucidated. Here we found that RAB26
promoted the integrity of adherens junctions (AJs) in a macroautophagy/autophagy
dependent manner in ALI. RAB26 is frequently downregulated in mouse lungs after
LPS treatment. Mice lacking Rab26 exhibited phosphorylated SRC expression and
increased CDH5/VE-cadherin phosphorylation, leading to AJ destruction. rab26-null
mice showed further aggravation of the effects of endotoxin insult on lung
vascular permeability and water content. Depletion of RAB26 resulted in
upregulation of phosphorylated SRC, enhancement of CDH5 phosphorylation, and
aggravation of CDH5 internalization, thereby weakening AJ integrity and
endothelial barrier function in human pulmonary microvascular endothelial cells
(HPMECs). RAB26 overexpression caused active interaction between SRC and the
autophagy marker LC3-II and promoted degradation of phosphorylated SRC.
Furthermore, RAB26 was involved in a direct and activation-dependent manner in
autophagy induction through interaction with ATG16L1 in its GTP-bound form. These
findings demonstrate that RAB26 exerts a protective effect on endothelial cell
(EC) permeability, which is in part dependent on autophagic targeting of active
SRC, and the resultant CDH5 dephosphorylation maintains AJ stabilization. Thus,
RAB26-mediated autophagic targeting of phosphorylated SRC can maintain barrier
integrity when flux through the RAB26-SRC pathway is protected. These findings
suggest that activation of RAB26-SRC signaling provides a new therapeutic
opportunity to prevent vascular leakage in ALI. ABBREVIATIONS: AJs: adherens
junctions; ALI: acute lung injury; ARDS: acute respiratory distress syndrome;
ATG5: autophagy related 5; ATG12: autophagy related 12; ATG 16L1: autophagy
related 16 like; 1 BALF: bronchoalveolar lavage fluidCQ: chloroquine; Ctrl:
control; EC: endothelial cell; GFP: green fluorescent protein; HA-tagged;
RAB26WT: HA-tagged wild-type; RAB26 HA-tagged; RAB26QL: HA-tagged; RAB26Q123LHA
tagged; RAB26NI: HA-tagged; RAB26N177IHPMECs: human pulmonary microvascular
endothelial cells; H&E: hematoxylin & eosin; IgG: immunoglobulin; GIF:
immunofluorescence; IP: immunoprecipitationi;. p.: intraperitoneal; LPS:
lipopolysaccharide; PBS: phosphate-buffered salinesi; RNA: small
interfering;RNASQSTM1/p62, sequestosome; 1TBS: Tris-buffered saline; VEGF:
vascular endothelial growth factor; WB: western blot; WT: wild-type.
PMID- 29965783
TI - Evaluation of visual pathways using visual evoked potentials in the patients with
impaired fasting glucose and impaired glucose tolerance.
AB - PURPOSE: There are many studies on degeneration of the ganglion cells using
visual evoked potential (VEP) in Diabetes mellitus (DM). The present study
intended to investigate whether the retinopathy findings would be helpful for
detecting the degeneration to develop or not in retinal ganglion cells with the
VEP test before being detectable in ophthalmoscopic examination on prediabetic
patients. MATERIALS AND METHODS: The present study was conducted prospectively
after obtaining approval from the Ethics Committee. In our study, the subjects
were divided into three groups as impaired fasting glucose (IFG), impaired
glucose tolerance (IGT) and normal patients. They also underwent physical,
ophthalmological and VEP examination. Three main components of VEP obtained from
these groups were N75, P100, and N145 latency and N75-P100 amplitude. RESULTS:
The study participants consisted of the IFG group (n: 30, female/male ratio:
21/9; mean age: 49.17 +/- 10.52 years), the IGT group (n: 30, female/male ratio:
23/7; mean age: 47.00 +/- 11.09 years), and the Control Group (n: 40, female/male
ratio: 30/10; mean age: 48.03 +/- 10.96 years). Difference in sex and age between
the study groups (p > 0.05). P100 latency was found to increase significantly in
comparison between the IGT and Control Group for both eyes (p right: 0.003, p
left: 0.001) whereas it did not increase significantly in the comparison between
the IFG and the Control Group (p right: 0.065, p left: 0.116). CONCLUSION: It was
observed that VEP may be a parameter of predictive value that might be used in
evaluating prediabetic cases in terms of retinopathies similar to DM.
PMID- 29965784
TI - Inflammatory Myofibrobalstic Tumor in Female Genital Tract.
AB - CONTEXT: - Inflammatory myofibroblastic tumor is a mesenchymal neoplasm of low
malignant potential. It was first described in lung, but is known to occur in
many extrapulmonary sites including female genital organs, most commonly the
uterus. It has a high recurrence rate and a low risk for metastasis. A more
recently described aggressive variant, epithelioid myofibroblastic sarcoma with a
predilection for the abdominal cavity of males, has also been recently reported
to occur in ovary. This tumor is composed of spindled and epithelioid
myofibroblasts in a variably myxoid stroma and commonly shows a fascicular growth
pattern with positive staining for desmin, smooth muscle actin, and CD10, which
may mimic a smooth muscle or endometrial stromal neoplasm. In the female genital
tract it has the potential for being misdiagnosed as a leiomyoma, endometrial
stromal tumor, or as a myxoid leiomyosarcoma, resulting in undertreatment or
overtreatment. It harbors rearrangements in the ALK gene, resulting in abnormal
expression of ALK protein. Immunostaining for ALK is a helpful diagnostic tool.
OBJECTIVE: - To provide a brief review of clinical, histologic,
immunohistochemical, and molecular features of inflammatory myofibroblastic tumor
with emphasis on possible diagnostic pitfalls in the female genital tract. DATA
SOURCES: - Review of pertinent literature on inflammatory myofibroblastic tumor
occurring in the female genital tract and personal experience of the authors.
CONCLUSIONS: - Inflammatory myofibroblastic tumor in the female genital tract can
mimic other more common benign and malignant tumors like leiomyoma,
leiomyosarcoma, and endometrial stromal sarcoma. Familiarity with clinical and
histologic features and use of ALK immunostaining can be critical for correct
diagnosis.
PMID- 29965786
TI - Corrigendum.
PMID- 29965785
TI - Prostate Cancers Detected by Magnetic Resonance Imaging-Targeted Biopsies Have a
Higher Percentage of Gleason Pattern 4 Component and Are Less Likely to Be
Upgraded in Radical Prostatectomies.
AB - CONTEXT: - In Gleason score GS (7) prostate cancers, the quantity of Gleason
pattern 4 (GP 4) is an important prognostic factor and influences treatment
decisions. Magnetic resonance imaging (MRI)-targeted biopsy has been increasingly
used in clinical practice. OBJECTIVE: - To investigate whether MRI-targeted
biopsy may detect GS 7 prostate cancer with greater GP 4 quantity, and whether it
improves biopsy/radical prostatectomy GS concordance. DESIGN: - A total of 243
paired standard and MRI-targeted biopsies with cancer in either standard or
targeted or both were studied, 65 of which had subsequent radical prostatectomy.
The biopsy findings, including GS and tumor volume, were correlated with the
radical prostatectomy findings. RESULTS: - More prostate cancers detected by MRI
targeted biopsy were GS 7 or higher. Mean GP 4 percentage in GS 7 cancers was
31.0% +/- 29.3% by MRI-targeted biopsy versus 25.1% +/- 29.5% by standard biopsy.
A total of 122 of 218 (56.0%) and 96 of 217 (44.2%) prostate cancers diagnosed on
targeted biopsy and standard biopsy, respectively, had a GP 4 of 10% or greater (
P = .01). Gleason upgrading was seen in 12 of 59 cases (20.3%) from MRI-targeted
biopsy and in 24 of 57 cases (42.1%) from standard biopsy ( P = .01). Gleason
upgrading correlated with the biopsy cancer volume inversely and GP 4 of 30% or
less in standard biopsy. Such correlation was not found in MRI-targeted biopsy.
CONCLUSIONS: - Magnetic resonance imaging-targeted biopsy may detect more
aggressive prostate cancers and reduce the risk of Gleason upgrading in radical
prostatectomy. This study supports a potential role for MRI-targeted biopsy in
the workup of prostate cancer and inclusion of percentage of GP 4 in the prostate
biopsy reports.
PMID- 29965787
TI - Secondary plasma cell leukemia: a multicenter retrospective study of 101
patients.
AB - This multicenter retrospective study included 101 patients (median age 62 years)
with secondary plasma cell leukemia (sPCL). The median time from initial multiple
myeloma diagnosis to sPCL was 31 months. Fifty-five out of 72 patients (75%) who
received any therapy were treated with immunomodulators (IMiDs) and/or proteasome
inhibitors (PIs), and 14/72 (19%) underwent salvage autologous stem cell
transplantation (ASCT). The overall response rate in patients who received ASCT
or PI (either alone or in combination) was higher than in those who did not (93%
vs. 36% and 60% vs. 30%, respectively). The median overall survival (OS) in
patients who received therapy was 4.2 months (95% CI: 1.3; 8.0) with a 1-year OS
of 19%. Platelet count <=100 * 109/L at sPCL diagnosis was the only independent
predictor of a poorer OS in treated patients (HR = 3.98, p = .0001). These
findings suggest that patients with sPCL may benefit from salvage ASCT- and PI
based regimens.
PMID- 29965788
TI - Mitochondrial regulation of [Ca2+]i oscillations during cell cycle resumption of
the second meiosis of oocyte.
AB - Oocyte is arrested at metaphase of the second meiosis until fertilization
switching on [Ca2+]i oscillations. Oocyte activation inefficiency is the most
challenging problem for failed fertilization and embryonic development.
Mitochondrial function and intracellular [Ca2+]i oscillations are two critical
factors for the oocyte's developmental potential. We aimed to understand the
possible correlation between mitochondrial function and [Ca2+]i oscillations in
oocytes. To this end, mitochondrial uncoupler CCCP which damages mitochondrial
function and two small molecule mitochondrial agonists, L-carnitine (LC) and BGP
15, were used to examine the regulation of [Ca2+]i by mitochondrial functions.
With increasing CCCP concentrations, [Ca2+]i oscillations were gradually
diminished and high concentrations of CCCP led to oocyte death. LC enhanced
mitochondrial membrane potential and [Ca2+]i oscillations and even improved the
damage induced by CCCP, however, BGP-15 had no beneficial effect on oocyte
activation. We have found that mitochondrial function plays a vital role in the
generation of [Ca2+]i oscillations in oocytes, and thus mitochondria may interact
with the ER to generate [Ca2+]i oscillations during oocyte activation.
Improvement of mitochondrial functions with small molecules can be expected to
improve oocyte activation and embryonic development in infertile patients without
invasive micromanipulation.
PMID- 29965789
TI - The Ruptured Achilles Tendon Elongates for 6 Months After Surgical Repair
Regardless of Early or Late Weightbearing in Combination With Ankle Mobilization:
A Randomized Clinical Trial.
AB - BACKGROUND: Treatment strategies for Achilles tendon rupture vary considerably,
and clinical outcome may depend on the magnitude of tendon elongation after
surgical repair. The aim of this project was to examine whether tendon
elongation, mechanical properties, and functional outcomes during rehabilitation
of surgically repaired acute Achilles tendon ruptures were influenced by
different rehabilitation regimens during the early postsurgical period.
HYPOTHESIS: Restricted early weightbearing that permits only limited motion about
the ankle in the early phase of tendon healing limits tendon elongation and
improves functional outcome. STUDY DESIGN: Randomized controlled trial; Level of
evidence, 1. METHODS: 75 consecutive patients with an acute Achilles tendon
rupture were included. They underwent surgical repair, and tantalum beads were
placed in the distal and proximal parts of the tendon; thereafter, the patients
were randomized into 3 groups. The first group was completely restricted from
weightbearing until week 7. The second group was completely restricted from
weightbearing until week 7 but performed ankle joint mobilization exercises. The
first and second groups were allowed full weightbearing after week 8. The third
group was allowed partial weightbearing from day 1 and full weightbearing from
week 5. All patients received the same instructions in home exercise guidelines
starting from week 9. RESULTS: The rehabilitation regimen in the initial 8 weeks
did not significantly influence any of the measured outcomes including tendon
elongation. Achilles tendon elongation and tendon compliance continued for up to
6 months after surgery, and muscle strength, muscle endurance, and patient
reported functional scores did not reach normal values at 12 months. CONCLUSION:
Differences in rehabilitation loading pattern in the initial 8 weeks after the
repair of an Achilles tendon rupture did not measurably alter the outcome. The
time to recover full function after an Achilles tendon rupture is at least 12
months. Registration: NCT02422004 ( ClinicalTrials.gov identifier).
PMID- 29965791
TI - Rivaroxaban: searching the integral vascular protection.
AB - INTRODUCTION: Residual cardiovascular risk remains high in patients with
atherosclerotic cardiovascular disease despite current antithrombotic therapy. On
the other hand, patients with atrial fibrillation have an increased risk of
myocardial infarction and cardiovascular death. As a result, a new antithrombotic
approach appears necessary to reduce this risk. Areas covered: In this article,
the role of rivaroxaban on vascular protection in patients with cardiovascular
disease and/or atrial fibrillation was reviewed, with a particular focus, but not
limited, on clinical trials. Expert commentary: Previous data have shown that
factor Xa plays a key role in the etiopathogenesis of atherothrombosis.
Experimental data suggest that rivaroxaban exhibits antiinflammatory and
antioxidative stress properties, and may improve endothelial dysfunction. The
COMPASS trial showed that among patients with stable atherosclerotic vascular
disease, the addition of rivaroxaban 2.5 mg twice daily (vascular dose) to
aspirin provided a higher cardiovascular protection than aspirin alone. In ROCKET
AF trial, compared with warfarin, rivaroxaban 20 mg once daily (15 mg if moderate
renal dysfunction) (anticoagulant dose) was, at least, as effective as warfarin
for the prevention of stroke or systemic embolism among patients with nonvalvular
atrial fibrillation, with a trend toward a reduction in the risk of
cardiovascular outcomes. All these data suggest that rivaroxaban might have a
vascular protective effect beyond its stroke/systemic embolism preventive
activity.
PMID- 29965790
TI - Preventing Emergency Vehicle Crashes: Status and Challenges of Human Factors
Issues.
AB - OBJECTIVE: This study reports current status of knowledge and challenges
associated with the emergency vehicle (police car, fire truck, and ambulance)
crashes, with respect to the major contributing risk factors. BACKGROUND:
Emergency vehicle crashes are a serious nationwide problem, causing injury and
death to emergency responders and citizens. Understanding the underlying causes
of these crashes is critical for establishing effective strategies for reducing
the occurrence of similar incidents. METHOD: We reviewed the broader literature
associated with the contributing factors for emergency vehicle crashes: peer
reviewed journal papers; and reports, policies, and manuals published by
government agencies, universities, and research institutes. RESULTS: Major risk
factors for emergency vehicle crashes identified in this study were organized
into four categories: driver, task, vehicle, and environmental factors. Also,
current countermeasures and interventions to mitigate the hazards of emergency
vehicle crashes were discussed, and new ideas for future studies were suggested.
CONCLUSION: Risk factors, control measures, and knowledge gaps relevant to
emergency vehicle crashes were presented. Six research concepts are offered for
the human factors community to address. Among the topics are emergency vehicle
driver risky behavior carryover between emergency response and return from a
call, distraction in emergency vehicle driving, in-vehicle driver assistance
technologies, vehicle red light running, and pedestrian crash control.
APPLICATION: This information is helpful for emergency vehicle drivers, safety
practitioners, public safety agencies, and research communities to mitigate crash
risks. It also offers ideas for researchers to advance technologies and
strategies to further emergency vehicle safety on the road.
PMID- 29965793
TI - miRNA 196a2(rs11614913) & 146a(rs2910164) polymorphisms & breast cancer risk for
women in an Iranian population.
AB - AIM: The purpose of our study was to analyze association of miRNAs
146aG/C(2910164) and 196a2C/T(11614913) polymorphism with breast cancer (BC) risk
for women of Azeri ethnicity in Iran. MATERIALS & METHODS: In the current case (n
= 200)-control (n = 200) study, miRNAs 146aG/C(2910164) and 196a2C/T(11614913)
were investigated for allelic and genotypic levels via the PCR-restriction
fragment length polymorphism technique. RESULTS: The statistical analysis showed
a significant relation between CC genotype of rs11614913(196a2) (codominant, odds
ratio (OR) = 0.58, p = 0.02236; recessive, OR = 2.92, p = 0.01695; overdominant,
OR = 0.44, p = 0.0113) and BC susceptibility. The subgroup analysis of mentioned
polymorphism declared the significant correlation (p <= 0.05) of the positive
abortion, regular menstruation, positive human epidermal receptor-2 and positive
estrogen receptor with BC susceptibility in CC genotype. CONCLUSION: The
existence of a C-allele at miRNA 196a2(11614913) elevates women's BC
susceptibility in Azeri ethnicity in Iran.
PMID- 29965792
TI - Relationship Between Range of Motion, Strength, Motor Control, Power, and the
Tennis Serve in Competitive-Level Tennis Players: A Pilot Study.
AB - BACKGROUND: The tennis serve is a complex skill requiring appropriate energy
transfer to maximize serve speed. As the only independently powered shot in
tennis, it is important to understand what characteristics contribute to a
player's serve. HYPOTHESIS: Upper extremity and lower extremity power variables
will be predictive of serve speed. STUDY DESIGN: Cross-sectional study. LEVEL OF
EVIDENCE: Level 3. METHODS: A total of 42 competitive tennis players underwent
range of motion, strength, motor control, power, and serve speed testing. Motion
assessment was completed for shoulder external and internal rotation, trunk
rotation, hip external and internal rotation, and ankle dorsiflexion. Strength
was assessed for the rotator cuff, scapula, and hip musculature. Motor control
was evaluated through upper and lower extremity Y-balance testing. Power
assessments were made using broad jump, single-leg hop, and seated unilateral
shot put testing. Pearson correlation was conducted to assess associations of
skill, height, and tested variables to serve speed. Significant variables were
used in a stepwise linear regression model, with serve speed as the dependent
variable. Variables are listed in relation to the participant's dominant arm.
RESULTS: Skill, height, contralateral hip external rotation range of motion,
nondominant arm Y-balance anterolateral reach, bilateral single-leg hops, and
seated unilateral shot put throws for both arms demonstrated significant positive
correlations to serve speed ( P < 0.05). Serve speed was predicted with 84%
variance through skill, height, contralateral hip external rotation range of
motion, ipsilateral single-leg hop, and the seated unilateral shot put throws.
CONCLUSION: The ability to generate increased serve speed is multifactorial. The
combination of skill, height, hip motion, and upper and lower extremity power may
determine serve speed. CLINICAL RELEVANCE: The findings suggest that motion,
motor control, and power testing should be evaluated when working with this
population to improve serve speed.
PMID- 29965795
TI - Implementation and initial outcomes of a spinal cord injury home care program at
a large veterans affairs medical center.
AB - OBJECTIVES: Describe an interdisciplinary spinal cord injury home care program
(SCIHCP), sample demographics for the veteran participants, and initial impact of
SCIHCP on health care utilization and mortality. DESIGN: Retrospective review.
SETTING: SCIHCP of the Spinal Cord Injury Center, VA North Texas Health Care
System (VANTHCS). PARTICIPANTS: Patients with SCI/D enrolled in the SCIHCP during
January 6, 2006 through January 9, 2012, whose injury occurred at least one year
prior to enrollment(n = 125). MAIN OUTCOME MEASURES: VANTHCS hospital admissions,
length of stay (LOS), and emergency department (ED) visits evaluated one year
before and one year after SCIHCP enrollment; mortality evaluated one-year post
enrollment. RESULTS: There were no significant changes in number of ED visits,
number of hospital admissions, or LOS over time. More home care visits and more
mental health comorbidities predicted more hospital admissions. Older patients
and those with more mental health comorbidities were more likely to experience
increases in LOS. These prediction models were significant after adjusting for
injury level, age, race, time since SCI, and number of medical comorbidities.
More home care visits were associated with lower likelihood of mortality post
enrollment. CONCLUSIONS: Inpatient and ED utilization did not change one year
after enrollment, but more SCIHCP visits predicted more hospital admissions and
lower likelihood of mortality in the post-evaluation year. The support,
education, and care continuity SCIHCP generates might be related to increased
inpatient access and lower mortality rate. Veterans with increased mental health
comorbidities used inpatient services more, and might need additional support.
PMID- 29965796
TI - Circadian period of luciferase expression shortens with age in human mature
adipocytes from obese patients.
AB - Daily rhythms in physiology and behavior change with age. An unresolved question
is to what extent such age-related alterations in circadian organization are
driven by the central clock in the suprachiasmatic nucleus (SCN), modifying
timing signals to contributing peripheral tissue oscillators, and are mediated by
underlying changes in the local cellular oscillators themselves. Using a
bioluminescence reporter approach, we sought to determine whether circadian clock
function in human adipocytes from subcutaneous (SAT) and visceral (VAT) adipose
tissues changes with age. SAT and VAT biopsies were obtained from obese
individuals during gastric bypass surgeries [ n = 16; body mass index: 44.8 +/-
11.4 kg/m2; age: 44 +/- 9 yr (range: 30-58)]. Cells were isolated and transduced
with a lentiviral circadian reporter construct [brain and muscle aryl hydrocarbon
receptor nuclear translocator-like:luciferase ( BMAL:LUC)], and bioluminescence
was recorded over a period of 3 d. Human BMAL1:LUC adipocytes displayed a robust
luminescence rhythm with comparable within-individual periods in mature and
preadipocytes ( P > 0.05). With increasing age, the circadian period decreased in
mature adipocytes ( P = 0.005) (beta = 4 min/yr; P < 0.05). Our ex vivo approach
indicated that ageing changes the organization of endogenous circadian
oscillators in human adipocytes, independent of SCN signaling.-Kolbe, I.,
Carrasco-Benso, M. P., Lopez-Minguez, J., Lujan, J., Scheer, F. A. J. L., Oster,
H., Garaulet, M. Circadian period of luciferase expression shortens with age in
human mature adipocytes from obese patients.
PMID- 29965794
TI - Oncogene-dependent addiction to carbohydrate-responsive element binding protein
in hepatocellular carcinoma.
AB - Metabolic reprogramming is a hallmark of many cancer types, including
hepatocellular carcinoma (HCC). Identifying the critical players in this process
might be crucial for the generation of novel and effective anti-neoplastic
therapies. In the present investigation, we determined the importance of
carbohydrate responsive element binding protein (ChREBP), a central player in the
regulation of lipid and glucose metabolism in the liver, on the development of
HCC in in vitro and in vivo models. We found that genetic deletion of ChREBP
(that will be referred to as ChREBPKO mice) strongly delays or impairs
hepatocarcinogenesis driven by AKT or AKT/c-Met overexpression in mice,
respectively. In contrast, HCC development was found to be completely unaffected
by ChREBP depletion in mice co-expressing AKT and N-Ras protooncogenes. In mouse
and human HCC cell lines, suppression of ChREBP via specific small interfering
RNAs (siRNAs) resulted in decreased proliferation and induction of apoptosis. Of
note, these cellular events were strongly augmented by concomitant inhibition of
the mitogen-activated protein kinase (MAPK) pathway. The present data indicate
that ChREBP activity might be required or dispensable for HCC growth, depending
on the oncogenes involved. In particular, the activation of Ras/MAPK signaling
might represent a possible mechanism of resistance to ChREBP depletion in this
tumor type. Additional studies are needed to unravel the molecular mechanisms
rendering HCC cells insensitive to ChREBP suppression.
PMID- 29965797
TI - Circadian variation in pulmonary inflammatory responses is independent of
rhythmic glucocorticoid signaling in airway epithelial cells.
AB - The circadian clock is a critical regulator of immune function. We recently
highlighted a role for the circadian clock in a mouse model of pulmonary
inflammation. The epithelial clock protein Bmal1 was required to regulate
neutrophil recruitment in response to inflammatory challenge. Bmal1 regulated
glucocorticoid receptor (GR) recruitment to the neutrophil chemokine, CXC
chemokine ligand 5 (CXCL5), providing a candidate mechanism. We now show that
clock control of pulmonary neutrophilia persists without rhythmic glucocorticoid
availability. Epithelial GR-null mice had elevated expression of proinflammatory
chemokines in the lung under homeostatic conditions. However, deletion of GR in
the bronchial epithelium blocked rhythmic CXCL5 production, identifying GR as
required to confer circadian control to CXCL5. Surprisingly, rhythmic pulmonary
neutrophilia persisted, despite nonrhythmic CXCL5 responses, indicating
additional circadian control mechanisms. Deletion of GR in myeloid cells alone
did not prevent circadian variation in pulmonary neutrophilia and showed reduced
neutrophilic inflammation in response to dexamethasone treatment. These new data
show GR is required to confer circadian control to some inflammatory chemokines,
but that this alone is insufficient to prevent circadian control of neutrophilic
inflammation in response to inhaled LPS, with additional control mechanisms
arising in the myeloid cell lineage.-Ince, L. M., Zhang, Z., Beesley, S.,
Vonslow, R. M., Saer, B. R., Matthews, L. C., Begley, N., Gibbs, J. E., Ray, D.
W., Loudon, A. S. I. Circadian variation in pulmonary inflammatory responses is
independent of rhythmic glucocorticoid signaling in airway epithelial cells.
PMID- 29965799
TI - Progress towards obtaining an HIV cure: slow but sure.
PMID- 29965798
TI - Improving knowledge and behavior of leadership and followership among the
interprofessional team.
AB - Objectives: To examine virtual training on Crew Resource Management (CRM)
principles of effective leadership and followership on participants' knowledge,
applicability, and intended behaviors. Methods: Graduate students (n=41) from
four health disciplines participated in the training, which included a self
learning module (e.g., didactic content and video vignettes) and an optional
virtual simulation exercise. Knowledge was examined via a 10-item pre/post
knowledge test. Applicability of the training and intended behaviors was measured
post-training via an 11-item survey. T-test and Analysis of variance were applied
to compare knowledge scores, as well as to determine variation in discipline
responses. Results: Knowledge improved significantly post-training (t(40)=10.47,
p<0.001). Pharmacy students scored significantly lower on the post-knowledge test
than medicine and nursing students [F(2,36)=5.99, p=0.006]. On average,
participants completing the module reported learning new skills and knowledge
(M=4.17, SD=0.54) and intended to use skills/knowledge gained from the training
in clinical practice (M=4.29, SD=0.56). No differences were noted among responses
from the various disciplines. Those completing the simulation exercise (n=10)
found value in the experience, again noting strong application to practice
(M=4.9, SD=0.32) and intended use in practice (M=4.9, SD=0.32). Conclusions: The
CRM training was valuable and applicable to practice. Use of a virtual platform
may provide an avenue for minimizing current barriers to successful
interprofessional education by allowing participants to connect in various
geographical locations. The module is ready for widespread use in health
professional education.
PMID- 29965800
TI - Management of patients with end-stage renal disease: coronary artery bypass graft
surgery versus percutaneous coronary intervention.
AB - PURPOSE OF REVIEW: Coronary artery disease is common in patients with end-stage
renal disease (ESRD) on hemodialysis. ESRD patients are prone to atherosclerosis
and are likely to present with advanced CAD requiring coronary artery bypass
graft surgery (CABG) or percutaneous coronary intervention (PCI). RECENT
FINDINGS: Individual observational studies and aggregated results comparing PCI
to CABG have shown an increased risk of early postoperative mortality in the CABG
group followed by a decrease in late mortality and cardiovascular events. Drug
eluting stents are preferred to bare metal stents in patients undergoing PCI.
Bilateral versus single internal thoracic arterial grafting strategies showed no
difference in survival, freedom from cardiac death or freedom from cardiac
events. There was no clear survival advantage to off-pump CABG over on-pump CABG
in ESRD patients. Evidence to support either CABG or PCI was limited to
retrospective observational studies that were at risk for treatment allocation
bias. SUMMARY: CABG carries an upfront risk of increased perioperative mortality
while demonstrating late survival benefit compared with PCI. Thus, in the context
of balancing these competing risks and benefits, deciding on the most appropriate
treatment in this high-risk cohort is challenging. Comprehensive patient
evaluation by a multidisciplinary team is strongly recommended.
PMID- 29965801
TI - Sex-specific risk factors for cardiovascular disease in women-making
cardiovascular disease real.
AB - PURPOSE OF REVIEW: Sex-specific differences in pathophysiology, prevalence, and
impact of cardiovascular disease (CVD) risk factors may explain the high
cardiovascular mortality rates in women. RECENT FINDINGS: We review the sex
differences in traditional risk factors (dyslipidemia, hypertension, diabetes,
and smoking) and nontraditional risk factors (menopause and hormones, pregnancy,
inflammation and autoimmune diseases, anemia, depression, and migraines) and
their prognostic and therapeutic implications. SUMMARY: Recent research indicates
that with respect to traditional risk factors such as dyslipidemia, hypertension,
diabetes, and smoking, women appear to have a similar risk of CVD when compared
to men. The risk is accelerated after menopause, possibly because of vascular and
lipid profile changes. Pregnancy offers a unique opportunity and window to screen
otherwise healthy women who may be at an increased risk of CVD in the future.
Clinicians should be aware of other novel risk factors including inflammation,
anemia, migraines, and depression, and further studies are warranted in order to
identify therapeutic implications for these conditions and CVD risk.
PMID- 29965802
TI - When the Standard Treatment Fails: Rituximab Therapy for Refractory TTP.
PMID- 29965803
TI - Endocrinopathies Related to Immune Checkpoint Inhibitors.
PMID- 29965804
TI - Risk of Venous Thromboembolic Events in Patients With Cancer Treated With
Aflibercept: A Systematic Review and Meta-Analysis of Randomized Controlled
Trials.
PMID- 29965805
TI - Fentanyl-Associated Serotonin Syndrome and Chest Wall Rigidity in an Intensive
Care Unit Patient.
PMID- 29965806
TI - Cetuximab-Associated Pneumatosis Intestinalis.
PMID- 29965807
TI - Treatment Patterns and Survival of Elderly Patients With Breast Cancer Brain
Metastases.
AB - OBJECTIVES: The main objective of this study was to analyze treatment patterns of
elderly patients with breast cancer brain metastases (BCBM), evaluate
characteristics associated with treatment selection, and to analyze trends in
overall survival (OS) over time. MATERIALS AND METHODS: We included women with
BCBM reported to the Surveillance, Epidemiology, and End Results Medicare Program
from 1992 to 2012. Treatments were recorded from Medicare claims from the date of
brain metastases diagnosis until 60 days after. Treatments included resection,
radiation, and chemotherapy. Cochran-Armitage tests were used for analysis of
treatment patterns. Multinomial logistic regression was applied to determine
factors associated with treatment selection. Cox regression modelled OS trends
within each treatment modality across time. RESULTS: Among 5969 patients
included, treatment rates increased from 50% in 1992 to 64.1% in 2012 (P<0.01).
Therapy combining radiation, resection, and/or chemotherapy also increased from
8.8% to 18% over the same period (P<0.01). Combined therapy was significantly
more likely among patients with extracranial metastases, those with estrogen
negative tumors, younger age at diagnosis, no comorbidities and more recently
diagnosed brain metastases. OS improved over time for patients who received a
combination of >=2 treatments (hazard ratio, 0.89 per every 5 more recent
diagnosis years; P<0.05). Older patients, those with extracranial metastases, or
estrogen/progesterone-negative tumors showed significantly shorter OS.
CONCLUSIONS: We observed substantial changes in treatment patterns and OS over
time in patients with BCBM. We identified several factors associated with
specific treatment use. Patients who underwent a combination of >=2 treatments
experienced a significant improvement in OS over time.
PMID- 29965808
TI - Contemporary approaches to High-risk, Early-Stage Serous Endometrial Cancer:
Clinical Equipoise Persists.
PMID- 29965809
TI - Dose Escalation in Stereotactic Body Radiation Therapy for Pancreatic Cancer: A
Meta-Analysis.
AB - OBJECTIVE: To determine whether increasing biologically effective dose (BED) with
stereotactic body radiation therapy (SBRT) is associated with improved local
control (LC) or toxicities in patients with locally advanced pancreatic cancer.
METHODS: A PICOS/PRISMA/MOOSE selection protocol was used to identify 15 studies
across 12 institutions in 5 countries where patients received definitive SBRT for
nonmetastatic disease. Biologically equivalent doses were calculated with an
alpha/beta of 10 (ie, BED10) for LC and acute toxicity and 3 (ie, BED3) for late
toxicity. Fixed and random effects models were used to characterize LC and grade
3/4 toxicities by BED. RESULTS: There were 508 patients included with a median
follow-up time of 9.1 months. The median dose was 30 Gy, and the most common
regimen was 30 Gy/5 fractions. There was no significant difference in LC rates at
1 year between the BED10<70 Gy versus >=70 Gy groups, with an estimate of 0.60
(95% confidence interval [CI], 0.36-0.81) versus 0.83 (95% CI, 0.63-0.97),
respectively. There was no significant difference in acute toxicity rates between
the BED10<70 Gy versus >=70 Gy groups, with an estimate of 0.02 (95% CI, 0.00
0.08) versus 0.05 (95% CI, 0.00-0.22), respectively. Given the dose distribution
across studies, 3 intervals were used to characterize BED3. There were no
significant differences in late toxicity among those receiving BED3<100, 100 to
200, or >200 Gy. CONCLUSIONS: SBRT for pancreatic cancer results in LC rates of
60% to 83% and clinically significant toxicity of <7%. Increasing BED10 beyond 70
Gy was not associated with increased rates of 1-year LC or acute toxicity.
Increasing BED3 beyond 100 Gy was not associated with increased rates of late
toxicity.
PMID- 29965810
TI - Rivaroxaban and dabigatran did not affect clotting profiles in plasma
reconstituted with varying levels of autologous platelets to the same degree as
heparin when evaluated using thromboelastography.
AB - OBJECTIVE: Current recommendations for treating patients with thromboembolism and
concomitant thrombocytopenia are based on anecdotal data and expert opinion,
rather than clinical studies. Our aim was to use an in-vitro model employing
thromboelastography (TEG) to evaluate clot formation as a surrogate indicator of
clinical tendency to hemorrhage, and investigate the interactions of plasma at
varying concentrations of platelets in the presence of anticoagulants. METHODS:
Platelet-rich and platelet-poor plasma isolated from whole blood were mixed
together to obtain platelet concentrations ranging from less than 10-150 * 10
platelets/l. Clotting was initiated with tissue factor and measured by TEG.
RESULTS: Different tissue factor concentrations were required to model clinical
clotting profiles for plasma that contained heparin (UFH), low molecular weight
heparin (LMWH), or fondaparinux. No tissue factor was required for rivaroxaban or
dabigatran-clotting reactions. The time to initiate coagulation (R) was
significantly delayed at platelet concentrations less than 30 * 10/l for UFH and
LMWH, less than 20 * 10/l for fondaparinux, and less than 10 * 10/l for
rivaroxaban and dabigatran. The strength of the clot was significantly
compromised at all platelet concentrations in the presence of UFH, LMWH or
fondaparinux. In contrast, rivaroxaban and dabigatran compromised clot strength
at platelet concentrations less than 10 * 10/l. CONCLUSION: All anticoagulants
tested compromised coagulation at specific platelet concentration thresholds.
Rivaroxaban and dabigatran had reduced impact on clot formation at low-platelet
concentrations compared with heparinoids, suggesting that the factor-specific
inhibitors may be more favorable than traditional heparin-based treatment of
thromboembolism in the presence of thrombocytopenia.
PMID- 29965811
TI - Leu33Pro (PlA) polymorphism of integrin beta3 modulates platelet Src pY418 and
focal adhesion kinase pY397 phosphorylation in response to abnormally high shear
stress.
AB - OBJECTIVES: Shear stress can activate platelet integrin-mediated signaling that
leads to shear-induced platelet aggregation (SIPA) and eventually contribute to
acute myocardial infarction. The major platelet integrin alphaIIbbeta3 is
polymorphic at residue 33 [Leu33Pro (PlA) polymorphism]. The Pro33 isoform has
been shown to have a prothrombotic phenotype. In this work, we studied the impact
of Leu33/Pro33 polymorphism on the shear-induced integrin-mediated Src and FAK
activation in platelets. METHODS: Platelets of both genotypes were placed on
immobilized fibrinogen or heat activated BSA and were exposed to physiological
(500/s) or abnormally high (5000/s) shear rates for 2-10 min. Platelets after
exposure to shear were analysed for Src pY418 and FAK pY397 activities. RESULTS:
Whereas physiological shear stress does not affect platelet signaling, abnormally
high-shear stress considerably elevates Src and FAK phosphorylation in both Pro33
and Leu33 platelets. Both under static and flow conditions, Pro33 platelets
exhibited a significantly higher Src and FAK activities than Leu33 platelets.
Interestingly, even in the absence of the alphaIIbbeta3-fibrinogen interaction,
we could detect a shear-induced integrin-mediated signaling of Src and FAK in
platelets. In parallel experiments in which platelets were pretreated with
abciximab, an integrin alphaIIbbeta3 antagonist, activation of both kinases by
shear was inhibited. CONCLUSION: Taken together, our data indicates an important
role of alphaIIbbeta3 and shows that Leu33Pro polymorphism modulates the integrin
mediated Src and FAK signaling in platelets in response to shear stress.
PMID- 29965812
TI - Preferences of Spine Surgeons With Regard to Management of Intraoperative
Durotomy: A Survey of Current Management.
AB - STUDY DESIGN: This was a cross-sectional study. OBJECTIVE: The objective of this
study was to determine spine surgeons' preferences for the intraoperative and
postoperative management of intraoperative durotomy (IDT) in decompression and
spinal fusion surgeries. SUMMARY OF BACKGROUND DATA: Management guidelines for
IDT remain elusive. Traditionally, management consists of intraoperative suturing
and postoperative bed rest. However, preferences of North American spine surgeons
may vary, particularly according to type of surgery. MATERIALS AND METHODS: Spine
surgeons of AO Spine North America (AOSNA) were surveyed online anonymously to
determine which techniques they preferred to manage IDT in decompression and
fusion. Differences in preferences according to surgery type were compared using
the Fisher exact test. A series of linear regressions were conducted to identify
demographic predictors of spine surgeons' preferences. RESULTS: Of 217
respondents, most were male (95%), orthopedic surgeons (70%), practiced at an
academic center (50%), were in practice 0-19 years (71%) and operated on 100-300
patients per year (70%). The majority of surgeons applied sutures (93%-96%) and
sealant (82%-84%). Surgeons also used grafts (26%-27%), drains (18%), other
techniques (4%-5%), blood patch (2%-3%), or no intraoperative management (1%-2%).
Postoperatively, most surgeons recommended bed rest (74%-75%). Antibiotics (22%),
immediate mobilization (18%-20%), reoperation (14%-16%), other techniques (6%),
or no postoperative management (5%) were also preferred. Management preferences
did not vary significantly between decompression and fusion surgeries (all P
values>0.05). Specialty, practice facility, years in practice, and patients per
year were identified as independent predictors of IDT management preferences
(P<0.05). CONCLUSIONS: Although North American spine surgeons preferred to manage
IDT with sutures augmented by sealant followed by bed rest after surgery, less
common techniques were also preferred during the intraoperative and postoperative
periods. Notably, intraoperative and postoperative IDT management preferences did
not change in accordance to the type of surgery being conducted. LEVEL OF
EVIDENCE: Level V.
PMID- 29965813
TI - Minimally Invasive Cervical Laminectomy for Cervical Spondylotic Myelopathy.
AB - OBJECTIVE: Cervical spondylotic myelopathy is a common cause of neurological
disability, especially in aging populations. There are several approaches to
decompress the cervical spinal cord, including anterior cervical discectomy and
fusion, corpectomy and fusion, arthroplasty, posterior cervical laminectomy with
or without fusion, and laminoplasty. Less well described is minimally invasive
cervical laminectomy. The authors report their technique and results for
minimally invasive cervical laminectomy. MATERIALS AND METHODS: The authors
describe in detail their surgical technique and results of 30 consecutive cases.
Preoperative and postoperative modified Japanese Orthopaedic Association (mJOA)
myelopathy scores were recorded. RESULTS: In total, 30 cases were included. Mean
age was 69 years (range, 57-89 y). Twelve procedures were at C3-4, 4 at C4-5, 5
at C5-6, 4 at C7-T1, 3 at C3-4 and C4-5, 1 at C4-5 and C5-6, and 1 at C5-6 and C6
7. Mean preoperative mJOA score was 12.1 (range, 4-15). Average length of surgery
was 142 minutes. Mean follow-up was 27 months (range, 3-64 mo). At 3 months, mean
postoperative mJOA score was 14.0 (range, 5-17). Mean mJOA improvement of 1.9 was
statistically significant (P<0.001). Seventeen patients had magnetic resonance
imaging (MRI) available at 3 months postoperatively (5 patients had no MRI, 3
patients had MRI contraindications, and 5 are pending). No MRI findings led to
further surgery. There were no durotomies and no wound infections. A single
patient had an unexplained new neurological deficit that resolved over 6 months.
CONCLUSIONS: Minimally invasive laminectomy for cervical myelopathy is safe and
effective and may be an underutilized procedure.
PMID- 29965814
TI - Association between Performance in a Maintenance of Certification Program and
Disciplinary Actions against the Medical Licenses of Anesthesiologists.
AB - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
BACKGROUND:: In 2000, the American Board of Anesthesiology (Raleigh, North
Carolina) began issuing time-limited certificates requiring renewal every 10 yr
through a maintenance of certification program. This study investigated the
association between performance in this program and disciplinary actions against
medical licenses. METHODS: The incidence of postcertification prejudicial license
actions was compared (1) between anesthesiologists certified between 1994 and
1999 (non-time-limited certificates not requiring maintenance of certification)
and those certified between 2000 and 2005 (time-limited certificates requiring
maintenance of certification); (2) within the non-time-limited cohort, between
those who did and did not voluntarily participate in maintenance of
certification; and (3) within the time-limited cohort, between those who did and
did not complete maintenance of certification requirements within 10 yr. RESULTS:
The cumulative incidence of license actions was 3.8% (587 of 15,486). The
incidence did not significantly differ after time-limited certificates were
introduced (hazard ratio = 1.15; 95% CI, 0.95 to 1.39; for non-time-limited
cohort compared with time-limited cohort). In the non-time-limited cohort, 10% (n
= 953) voluntarily participated in maintenance of certification. Maintenance of
certification participation was associated with a lower incidence of license
actions (hazard ratio = 0.60; 95% CI, 0.38 to 0.94). In the time-limited cohort,
90% (n = 5,329) completed maintenance of certification requirements within 10 yr
of certificate issuance. Not completing maintenance of certification requirements
(n = 588) was associated with a higher incidence of license actions (hazard ratio
= 4.61; 95% CI, 3.27 to 6.51). CONCLUSIONS: These findings suggest that meeting
maintenance of certification requirements is associated with a lower likelihood
of being disciplined by a state licensing agency. The introduction of time
limited certificates in 2000 was not associated with a significant change in the
rate of license actions.
PMID- 29965815
TI - False-positive Transesophageal Echocardiography after False-positive Computed
Tomography Angiography in Suspected Type A Aortic Dissection.
PMID- 29965816
TI - Gone Fishing....
PMID- 29965817
TI - Postoperative Delirium and Postoperative Cognitive Dysfunction: Two Sides of the
Same Coin?
PMID- 29965818
TI - Transtracheal Use of the CriCath Cannula in Combination With the Ventrain Device
for Prevention of Hypoxic Arrest due to Severe Upper Airway Obstruction: A Case
Report.
AB - A patient recently treated with surgery and radiation for oropharyngeal cancer
presented with impending hypoxic respiratory and cardiac arrest in a difficult
airway scenario. A CriCath cannula in combination with the Ventrain device and
its active expiratory ventilation technology enabled oxygenation and ventilation
for 60 minutes until a surgical airway was established. This case report is the
first to describe the intended use of Ventrain technology in an emergent "can't
ventilate-can't intubate" scenario.
PMID- 29965819
TI - Chikungunya in Children: A Clinical Review.
AB - Chikungunya (CHIKV) is an emerging arboviral infection with recent spikes in
transmission in the Americas. Chikungunya is most commonly transmitted by
mosquitos, specifically Aedes aegypti and Aedes albopictus. These mosquitoes are
found throughout many parts of the United States. The classic tetrad of symptoms
for CHIKV is fever, symmetric polyarthralgia, maculopapular rash, and nonpurulent
conjunctivitis. Although the majority (3 of 4) of infected people will be
symptomatic, the viral illness generally runs a benign course. Nevertheless, when
compared with infected adults, children more commonly have neurological and
dermatological symptoms and are less likely to have arthralgia. The key
differential diagnosis to consider is dengue, which has greater immediate
morbidity and which can cause coinfection. Local health departments facilitate
diagnostic testing, using either RNA polymerase chain reaction or antibody
screening based on the timing of presentation. Management is supportive. The
purpose of this review article is to provide readers basic knowledge regarding
the microbiology, epidemiology, risk factors for transmission, and typical
clinical presentation of CHIKV. A practical approach to diagnosis and management
of infected children is provided.
PMID- 29965820
TI - Chikungunya in Children: A Clinical Review.
PMID- 29965821
TI - Interventions to Increase Point-of-Care Ultrasound Use in a Pediatric Emergency
Department.
AB - OBJECTIVE: We sought to determine which interventions have effectively increased
point-of-care ultrasound (US) use in a pediatric emergency department (ED).
DESIGN/METHODS: We evaluated the impact of specific interventions conducted over
a 5-year period (2010-2015) on point-of-care US performance in a tertiary care
pediatric ED. Ultrasound use by attending physicians and fellows was ascertained
from a departmental database. Interventions assessed included the following: (1)
initiation of an US fellowship, (2) acquisition of a second US machine, (3)
performance of an US-related research project in the department, (4) initiation
of faculty US curriculum, (5) earlier introduction of US education for pediatric
emergency medicine fellows, and (6) administrative mandate dictating faculty
requirements for credentialing. Mean monthly US use was trended over time using
statistical process control methodology, and the impact of major interventions
was analyzed using interrupted time-series analyses. RESULTS: The mean number of
US scans increased from 2.0 to 5.9 per attending per month and from 4.3 to 7.1
per fellow per month over the study period. Using interrupted time-series
analyses, we observed the only intervention to significantly increase attending
US utilization was an administrative credentialing mandate, with an associated
increase of 6% per month (incidence rate ratio, 1.06; 95% confidence interval,
1.01-1.11). CONCLUSIONS: Point-of-care US use has increased over time for both
fellows and attending physicians. We observed that an administrative mandate led
to a significant increase in US use among attending physicians.
PMID- 29965822
TI - Interpersonal Relationships Among Black Couples and Depressive Symptoms During
Pregnancy.
AB - OBJECTIVE: The purpose of this study was to examine associations of the mother
father relationship and social support with depressive symptoms during pregnancy
among Black mothers and fathers. METHODS: Fifty Black mother-father dyads from
the Midwest completed a packet of questionnaires that included conflict with
partner, social support, depressive symptoms, and sociodemographic
characteristics. RESULTS: Twenty-four percent of mothers and 16% of fathers had
Center for Epidemiological Studies-Depression scores >=23, which have been
correlated with a major depression diagnosis. There were no differences in
depressive symptoms between mothers and fathers. Fathers reporting high
depressive symptoms were not more likely to be partnered with mothers reporting
high depressive symptoms. Controlling for age, higher levels of conflict with
partner, and lower levels of social support predicted higher levels of depressive
symptoms for both mothers and fathers. CLINICAL IMPLICATIONS: Black expectant
mothers and fathers may be at risk for clinical depression. Fathers experienced
comparable levels of depressive symptoms with mothers, indicating the need to
consider fathers' psychological adjustment during pregnancy. Higher levels of
conflict with partner and lower levels of social support predicted higher levels
of depressive symptoms for both parents. Maternal-child nurses should assess for
mothers' as well as fathers' experiences of depressive symptoms and the mother
father relationship when providing prenatal care.
PMID- 29965823
TI - Psychotherapeutic Treatments for Depression During Pregnancy.
AB - Depression during pregnancy is a significant public health problem that is
associated with adverse consequences for women and children. Despite the
availability of treatment options, depression during pregnancy is often
undertreated. Most pregnant women prefer nonpharmacological interventions over
antidepressant medications. We review the evidence base for psychotherapeutic
treatment approaches to depression during pregnancy. Treatments reviewed include
interpersonal therapy, cognitive-behavioral therapy, behavioral activation, and
mindfulness-based cognitive therapy. We review both traditional face-to-face
delivery and digital interventions. We conclude with recommendations for
treatment preferences, collaborative decision-making, and strategies to improve
uptake of such services among prenatal women.
PMID- 29965824
TI - The legacy of Cherry Ames.
PMID- 29965825
TI - Infection prevention and control core practices: A roadmap for nursing practice.
PMID- 29965826
TI - A Standardized Approach to Electronic Fetal Monitoring in Critical Care
Obstetrics.
AB - From the periphery, pregnancy is a common event in women of childbearing age.
Normal anatomic and physiologic adaptations occur and, in most cases, will result
in ideal maternal-fetal outcomes. Yet, every day, obstetric clinicians are facing
complex pregnancies with complicated life-threatening conditions or coexisting
medical and surgical problems that not only alter maternal physiology but also
impact fetal survival. A challenge in this population is individualizing maternal
fetal care in critical care women while integrating medical-surgical specialties
in creating an interdisciplinary team with similar management goals. Questions
frequently arise concerning admission criteria, location of care, as well as type
and mix of personnel. Furthermore, how to simultaneously manage a critically ill
parturient while monitoring a viable fetus is often obscured. This article
focuses on crucial fetal monitoring concepts using a standardized approach to
interpretation and management in pregnancies managed in an intensive care
environment. Application of fetal monitoring during surgical procedures, during
perimortem cesarean birth, and in women who have irreversible loss of brain
function is included.
PMID- 29965827
TI - Outpatient High-dose Methotrexate for Osteosarcoma: It's Safe and Feasible, If
You Want It.
AB - BACKGROUND: High-dose methotrexate (HD MTX) is usually administered as an
inpatient to those with osteosarcoma. We prospectively tested the safety and
feasibility of administering HD MTX in the ambulatory setting. MATERIALS AND
METHODS: In this single arm prospective observational study, eligible patients
had previously completed 2 courses of HD MTX as an inpatient. On study, patients
received MTX in hospital, discharged home and returned for daily assessment.
Criteria to determine safety and feasibility included: (1) parent compliance with
home instructions, (2) pump functioning/failure, and/or (3) admission for
toxicity/noncompliance. Outpatient therapy was deemed feasible if <25% courses
resulted in study event. Patient satisfaction was assessed. RESULTS: Six patients
(median age, 13.5 y) with extremity osteosarcoma completed 35 courses of MTX.
There were no study events-no hospitalizations or pump failures and all parents
were compliant. The Data and Safety Committee concluded that with zero events in
35 courses, it was unlikely for outpatient MTX to be infeasible; study was thus
terminated early. Participants reported value to stay out of hospital, permitted
life to feel "more normal"; however, burden of daily commute to hospital was
cited. CONCLUSIONS: The delivery of HD MTX is safe and feasible in patients with
osteosarcoma.
PMID- 29965828
TI - Incidence of congenital idiopathic clubfoot in the Netherlands.
AB - The incidence of clubfoot patients is an important factor for centralization of
care. Medical records of 21 accredited clubfoot centers were selected using the
diagnosis treatment codes and checked to confirm diagnosis. All idiopathic
clubfoot cases born during 2013-2014 were analyzed with respect to sex, affected
foot, regional distribution, and seasonal variation. Among the 346 522 live
births, 377 idiopathic clubfoot cases were registered. The incidence of the
congenital idiopathic clubfoot in the Netherlands during 2013 and 2014 was 1.09
per 1000 live births, indicating that every year, ~200 children with one or two
clubfeet are born in the Netherlands. On the basis of this finding, we can start
to refine clubfoot care.
PMID- 29965829
TI - Lionfish venom elicits pain predominantly through the activation of
nonpeptidergic nociceptors.
AB - The lionfish (Pterois volitans) is a venomous invasive species found in the
Caribbean and Northwestern Atlantic. It poses a growing health problem because of
the increase in frequency of painful stings, for which no treatment or antidote
exists, and the long-term disability caused by the pain. Understanding the
venom's algogenic properties can help identify better treatment for these
envenomations. In this study, we provide the first characterization of the pain
and inflammation caused by lionfish venom and examine the mechanisms through
which it causes pain using a combination of in vivo and in vitro approaches
including behavioral, physiological, calcium imaging, and electrophysiological
testing. Intraplantar injections of the venom produce a significant increase in
pain behavior, as well as a marked increase in mechanical sensitivity for up to
24 hours after injection. The algogenic substance(s) are heat-labile peptides
that cause neurogenic inflammation at the site of injection and induction of Fos
and microglia activation in the superficial layers of the dorsal horn. Finally,
calcium imaging and electrophysiology experiments show that the venom acts
predominantly on nonpeptidergic, TRPV1-negative, nociceptors, a subset of neurons
implicated in sensing mechanical pain. These data provide the first
characterization of the pain and inflammation caused by lionfish venom, as well
as the first insight into its possible cellular mechanism of action.
PMID- 29965831
TI - Bilateral Ultasound Guided Erector Spinae Plane Block for Postoperative Pain
Management in Lumbar Spine Surgery: A Case Series.
PMID- 29965830
TI - Estimating relative efficacy in acute postoperative pain: network meta-analysis
is consistent with indirect comparison to placebo alone.
AB - Network meta-analysis uses direct comparisons of interventions within randomized
controlled trials and indirect comparisons across them. Network meta-analysis
uses more data than a series of direct comparisons with placebo, and
theoretically should produce more reliable results. We used a Cochrane overview
review of acute postoperative pain trials and other systematic reviews to provide
data to test this hypothesis. Some 261 trials published between 1966 and 2016
included 39,753 patients examining 52 active drug and dose combinations (27,726
given active drug and 12,027 placebo), in any type of surgery (72% dental). Most
trials were small; 42% of patients were in trials with arms <50 patients, and 27%
in trials with arms >=100 patients. Response to placebo in third molar extraction
fell by half in studies over 30 to 40 years (171 trials, 7882 patients given
placebo). Network meta-analysis and Cochrane analyses provided very similar
results (average difference 0.04 number needed to treat units), with no
significant difference for almost all comparisons apart from some with small
patient numbers or small effect size, or both. Network meta-analysis did not
detect significant differences between effective analgesics. The similarity
between network meta-analysis and Cochrane indirect analyses probably arose from
stringent quality criteria in trials accepted in Cochrane reviews (with
consequent low risk of bias) and consistency in methods and outcomes. Network
meta-analysis is a useful analytical tool that increases our confidence in
estimates of efficacy of analgesics in acute postoperative pain, in this case by
providing similar results.
PMID- 29965832
TI - Scalp Block for Management of Subarachnoid Hemorrhage (SAH)-induced Headache.
PMID- 29965833
TI - Presenting Symptoms Independently Predict Mortality in Septic Shock: Importance
of a Previously Unmeasured Confounder.
AB - OBJECTIVES: Presenting symptoms in patients with sepsis may influence rapidity of
diagnosis, time-to-antibiotics, and outcome. We tested the hypothesis that vague
presenting symptoms are associated with delayed antibiotics and increased
mortality. We further characterized individual presenting symptoms and their
association with mortality. DESIGN: Retrospective cohort study. SETTING:
Emergency department of large, urban, academic U.S. hospital. PATIENTS: All adult
patients with septic shock treated in the emergency department between April 2014
and March 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 654 septic
shock cases, 245 (37%) presented with vague symptoms. Time-to-antibiotics from
first hypotension or elevated lactate was significantly longer for those with
vague symptoms versus those with explicit symptoms of infection (1.6 vs 0.8 hr; p
< 0.01), and in-hospital mortality was also substantially higher (34% vs 16%; p <
0.01). Patients with vague symptoms were older and sicker as evidenced by triage
hypotension, Sequential Organ Failure Assessment score, initial serum lactate,
and need for intubation. In multivariate analysis, vague symptoms were
independently associated with mortality (adjusted odds ratio, 2.12; 95% CI, 1.32
3.40; p < 0.01), whereas time-to-antibiotics was not associated with mortality
(adjusted odds ratio, 1.01; 95% CI, 0.94-1.08; p = 0.78). Of individual symptoms,
only the absence of fever, chills, or rigors (odds ratio, 2.70; 95% CI, 1.63
4.47; p < 0.01) and presence of shortness of breath (odds ratio, 1.97; 95% CI,
1.23-3.15; p < 0.01) were independently associated with mortality. CONCLUSIONS:
More than one third of patients with septic shock presented to the emergency
department with vague symptoms that were not specific to infection. These
patients had delayed antibiotic administration and higher risk of mortality even
after controlling for demographics, illness acuity, and time-to-antibiotics in
multivariate analysis. These findings suggest that the nature of presenting
symptoms is an important component of sepsis clinical phenotyping and may be an
important confounder in sepsis epidemiologic studies.
PMID- 29965834
TI - Diagnostic Ultrasound and Microbubbles Treatment Improves Outcomes of Coronary No
Reflow in Canine Models by Sonothrombolysis.
AB - OBJECTIVES: Effective treatment for microvascular thrombosis-induced coronary no
reflow remains an unmet clinical need. This study sought to evaluate whether
diagnostic ultrasound and microbubbles treatment could improve outcomes of
coronary no-reflow by dissolving platelet- and erythrocyte-rich microthrombi.
DESIGN: Randomized controlled laboratory investigation. SETTING: Research
laboratory. SUBJECTS: Mongrel dogs. INTERVENTIONS: Coronary no-reflow models
induced by platelet- or erythrocyte-rich microthrombi were established and
randomly assigned to control, ultrasound, recombinant tissue-type plasminogen
activator, ultrasound + microbubbles, or ultrasound + microbubbles + recombinant
tissue-type plasminogen activator group. All treatments lasted for 30 minutes.
MEASUREMENTS AND MAIN RESULTS: Percentage of microemboli-obstructed coronary
arterioles was lower in ultrasound + microbubbles group than that in control
group for platelet- (> 50% obstruction: 10.20% +/- 3.56% vs 31.80% +/- 3.96%; <
50% obstruction: 14.80% +/- 4.15% vs 28.20% +/- 3.56%) and erythrocyte-rich
microthrombi (> 50% obstruction: 8.20% +/- 3.11% vs 30.60% +/- 4.83%; < 50%
obstruction: 12.80% +/- 4.15% vs 25.80% +/- 3.70%) (p < 0.001). Percentage change
of myocardial blood flow in left anterior descending artery-dominated region,
left ventricular ejection fraction, fractional shortening, and ST-segment
resolution were higher, whereas infarcted area, troponin I, and creatine kinase
MB isoenzyme were lower in ultrasound + microbubbles group than that in control
group for both types of microthrombi (p < 0.001). Percentage change of myocardial
blood flow, ejection fraction, fractional shortening, and ST-segment resolution
were higher, whereas infarcted area, troponin I, and creatine kinase MB isoenzyme
were lower in ultrasound + microbubbles and ultrasound + microbubbles +
recombinant tissue-type plasminogen activator groups than that in recombinant
tissue-type plasminogen activator group for platelet-rich microthrombi (p <
0.05). CONCLUSIONS: Ultrasound + microbubbles treatment could dissolve platelet-
and erythrocyte-rich microthrombi, thereby improving outcomes of coronary no
reflow, making it a promising supplement to current reperfusion therapy for acute
ST-segment elevation myocardial infarction.
PMID- 29965835
TI - Acute Respiratory Failure in Pediatric Hematopoietic Cell Transplantation: A
Multicenter Study.
AB - OBJECTIVES: Acute respiratory failure is common in pediatric hematopoietic cell
transplant recipients and has a high mortality. However, respiratory prognostic
markers have not been adequately evaluated for this population. Our objectives
are to assess respiratory support strategies and indices of oxygenation and
ventilation in pediatric allogeneic hematopoietic cell transplant patients
receiving invasive mechanical ventilation and investigate how these strategies
are associated with mortality. DESIGN: Retrospective, multicenter investigation.
SETTING: Twelve U.S. pediatric centers. PATIENTS: Pediatric allogeneic
hematopoietic cell transplant recipients with respiratory failure. INTERVENTIONS:
None. MEASUREMENTS AND MAIN RESULTS: Two-hundred twenty-two subjects were
identified. PICU mortality was 60.4%. Nonsurvivors had higher peak oxygenation
index (38.3 [21.3-57.6] vs 15.0 [7.0-30.7]; p < 0.0001) and oxygen saturation
index (24.7 [13.8-38.7] vs 10.3 [4.6-21.6]; p < 0.0001), greater days with FIO2
greater than or equal to 0.6 (2.4 [1.0-8.5] vs 0.8 [0.3-1.6]; p < 0.0001), and
more days with oxygenation index greater than 18 (1.4 [0-6.0] vs 0 [0-0.3]; p <
0.0001) and oxygen saturation index greater than 11 (2.0 [0.5-8.8] vs 0 [0-1.0];
p < 0.0001). Nonsurvivors had higher maximum peak inspiratory pressures (36.0 cm
H2O [32.0-41.0 cm H2O] vs 30.0 cm H2O [27.0-35.0 cm H2O]; p < 0.0001) and more
days with peak inspiratory pressure greater than 31 cm H2O (1.0 d [0-4.0 d] vs 0
d [0-1.0 d]; p < 0.0001). Tidal volume per kilogram was not different between
survivors and nonsurvivors. CONCLUSIONS: In this cohort of pediatric
hematopoietic cell transplant recipients with respiratory failure in the PICU,
impaired oxygenation and use of elevated ventilator pressures were common and
associated with increased mortality.
PMID- 29965836
TI - Early recruitment of coronary collateral circulation: impact in late presentation
nonreperfused acute coronary occlusion.
AB - BACKGROUND: Debate still remains on whether the presence of early recruited
collateral circulation (ERCC) in the setting of an acute coronary occlusion (ACO)
has a prognosis benefit. Some previous reports have shown lower mortality and
morbidity rates in well-collateralized patients compared with those with poorly
recruited collateral circulation (PCC), but others have not. In the primary
angioplasty era, the role of collateral circulation in these studies may have
been influenced by the effect of early reperfusion. The actual impact of ERCC in
ACO can be clarified by studying its effect on nonreperfused patients. OBJECTIVE:
This study aimed to compare the 1-year clinical outcome in nonreperfused late
presentation ACO in a major coronary artery with ERCC versus PCC. PATIENTS AND
METHODS: Between 2008 and 2015, we included 164 patients with a nonreperfused
late presentation ACO. The patients were divided according to the presence of
angiographic ERCC (Rentrop 2-3) or PCC (Rentrop 0-1). ERCC was present in 54% of
patients. Patients with ERCC less often presented with cardiogenic shock (P=0.02)
and the right coronary artery was the most frequent culprit vessel (P=0.02). The
presence of PCC was associated independently with higher 1-year cardiovascular
mortality [hazard ratio (HR): 6.92; 95% confidence interval (95%CI): 1.37-34.7;
P=0.019], 1-year total mortality (HR: 5.79; 95%CI: 1.95-17.1; P=0.001), and 1
year major adverse cardiac event (HR: 8.05; 95%CI: 1.73-37.4; P<0.01).
CONCLUSION: The presence of angiographically PCC in the setting of late
presentation nonreperfused ACO is relatively infrequent (46%) and is associated
with worse 1-year major clinical outcomes.
PMID- 29965837
TI - Quantitative flow ratio and instantaneous wave-free ratio for the assessment of
the functional severity of intermediate coronary artery stenosis.
AB - OBJECTIVE: Quantitative flow ratio (QFR) is a novel physiological index of the
severity of coronary stenosis. The aim of the present study was to investigate
the relationship between QFR and the instantaneous wave-free ratio (iFR).
PATIENTS AND METHODS: We analyzed contrast-flow QFR, iFR, and fractional flow
reserve (FFR) in 100 coronary arteries with intermediate stenosis. RESULTS: There
was a high correlation (r=0.71, P<0.001) and a good agreement (mean difference:
0.09+/-0.11) between QFR and iFR. Both QFR and iFR were correlated significantly
with FFR (r=0.89, P<0.001 and r=0.76, P<0.001, respectively). The mean absolute
difference between FFR and QFR was significantly smaller than that between FFR
and iFR (-0.01+/-0.07 vs. -0.08+/-0.09, P<0.001). The diagnostic accuracy of QFR
less than or equal to 0.80 for predicting FFR less than or equal to 0.80 was
numerically higher than that of iFR less than or equal to 0.89 for predicting FFR
less than or equal to 0.80 [QFR: 94% (95% confidence interval: 85-97%) vs. iFR:
74% (95% confidence interval: 65-81%)]. CONCLUSION: QFR was correlated highly
with iFR as well as FFR. Like FFR and iFR, QFR might be reliable for assessing
the physiological severity of coronary stenosis in the angiographic intermediate
lesions.
PMID- 29965839
TI - We want to hear about you!: 2018 Richard Hader Visionary Leader Award.
PMID- 29965840
TI - How to drive employee engagement through high-performance leadership.
PMID- 29965838
TI - Coronary artery calcium score in predicting periprocedural myocardial infarction
in patients undergoing an elective percutaneous coronary intervention.
AB - BACKGROUND: This study aimed to evaluate whether the coronary artery calcium
score (CACS) measured with computed tomography coronary angiography (CTCA)
predicts periprocedural myocardial infarction (PMI) in patients undergoing an
elective percutaneous coronary intervention (PCI). PATIENTS AND METHODS: A total
of 197 patients with stable angina underwent elective PCI after CTCA. We
evaluated CACS using CTCA and assessed the clinical risk factors for PMI. PMI was
defined as an elevation of troponin I levels exceeding five times the upper limit
of normal within 24 h after PCI. Patients were followed up for major adverse
cardiovascular events for a median of 4.6 years. RESULTS: The prevalence of PMI
was 18.7% (37 patients) and patients with PMI showed a trend toward a higher CACS
(721+/-779 vs. 498+/-842, P=0.142). The prevalence of PMI showed a positive
correlation with the CACS distribution [8.0%, first interquartile range (IQR);
14.3%, second IQR; 22.4%, third IQR; 30.6%, fourth IQR; P=0.002]. The CACS cut
off value for PMI was greater than 113 (area under the curve: 0.670; 95%
confidence interval: 0.600-0.736; P<0.001). Patients with CACS greater than 113
before PCI showed a higher prevalence of PMI (26.2 vs. 5.6%, odds ratio: 5.994;
P<0.001). Multivariate analysis showed that CACS greater than 113 was the main
predictor for PMI (odds ratio: 3.61, 95% confidence interval: 1.145-11.363;
P=0.028). In this study, the cumulative incidence of major adverse cardiovascular
event was higher in patients with PMI (54.1 vs. 10.6%; P<0.001). CONCLUSION: This
study suggests that high CACS measured with CTCA influences the occurrence of
PMI, which is associated with worse cardiovascular outcomes.
PMID- 29965841
TI - Are we ready for precision health?
PMID- 29965842
TI - Shared governance councils: 10 essential actions for nurse leaders.
PMID- 29965843
TI - Two heads are better than one: Partnering to improve a critical care work
environment.
PMID- 29965845
TI - Join us in September for Nursing Management Congress2018!
PMID- 29965844
TI - Charge nurse development: What does the literature say?
PMID- 29965846
TI - A letter to novice nurse leaders.
PMID- 29965848
TI - Engage new nurses with CARING.
PMID- 29965847
TI - Tips for emotional agility.
PMID- 29965849
TI - What is new in paediatric uveitis?
AB - PURPOSE OF REVIEW: The aim of this study was to summarize the demographics and
causes of paediatric uveitis and to discuss the latest treatment options for
noninfectious paediatric uveitis. RECENT FINDINGS: In the last few years, reports
out of Europe, Asia and the Americas have shown that the causes of paediatric
uveitis can vary greatly geographically. With ongoing research into therapeutics,
particularly the development of biologic agents, the treatment of noninfectious
entities has evolved over time. SUMMARY: Epidemiology data show that most
paediatric uveitis cases worldwide are chronic and have noninfectious causes.
Fortunately, we have more treatment options than ever to combat these sight
threatening diseases.
PMID- 29965850
TI - Trachoma elimination, approaching 2020.
AB - PURPOSE OF REVIEW: To review current practices for trachoma treatment with a
focus on recent studies, particularly those discussing trachoma trichiasis
surgery. RECENT FINDINGS: Azithromycin eye drops twice daily for 3 days may be as
efficient as oral azithromycin in treating active trachoma. Facial cleanliness
and environmental improvement programming should employ a variety of behavior
change techniques to give sustained improvements. Posterior lamellar tarsal
rotation carries a lower risk for trichiasis recurrence and is more effective in
severe trachoma trichiasis than bilamellar tarsal rotation. Tarsoconjunctival
incision can play a pivotal role in trichiaisis recurrence. Tarsus-sparing
procedures continue to be refined with good success rates. Concurrent correction
of lid abnormalities that commonly occur with trachoma trichiasis may maximize
the result of surgery. SUMMARY: Better understanding of the pathophysiology of
trachoma and postoperative trichiasis recurrence is critical for effective
trachoma control. Progressive tarsoconjunctival scarring in trachoma and high
recurrence rates following tarsal rotation procedures raise the importance of
adopting a procedure that spares tarsus/conjunctiva.
PMID- 29965851
TI - Complex Aphthae Treated With Apremilast.
PMID- 29965852
TI - Polyarteritis Nodosa and Membranous Glomerulonephritis: Two Simultaneous
Extrahepatic Manifestations of Hepatitis B.
PMID- 29965853
TI - Validity of 7-Joint Versus Simplified 12-Joint Ultrasonography Scoring Systems in
Assessment of Rheumatoid Arthritis Activity.
AB - INTRODUCTION: Musculoskeletal ultrasonography (US) is an objective tool for the
evaluation of disease activity in rheumatoid arthritis (RA) patients. There is no
consensus on the exact number of joints that should be examined. Examination of
reduced joint count is more practical than the comprehensive one. OBJECTIVES:
This is a cross-sectional study investigated the validity of a 7-joint US score
(US7) in assessment of joint inflammation in RA patients compared with a
simplified 12-joint US score (US12) and correlated both to composite disease
activity indices. METHODS: The activity status of 50 RA patients was assessed
clinically and ultrasonographically. The disease activity was calculated using 3
composite indices. Ultrasonography was performed by 1 blinded rheumatologist,
using power Doppler (PD) and gray-scale (GS) US examination. The US7 and
simplified US12 were performed as originally described. However, the GS synovitis
and PD synovitis of US12 were computed in 2 separate scores instead of 1. Two sum
US7 scores were added, sum (GS) US7 and sum (PD) US7 after summating synovitis
and tenosynovitis scores. Ultrasonography interobserver/intraobserver reliability
was evaluated on 40 stored images. RESULTS: Correlation coefficient between the
different ultrasonographic scores showed no difference. The GS scores showed no
correlation with disease activity parameters; however, the PD scores did. The sum
(PD) US7 was the only score that showed significant correlation with the 3
different composite disease indices. CONCLUSIONS: All studied US scores proved
valid in assessment of disease activity status in RA. This is in favor of using
the less-time-consuming US7 scores. The strongest correlation found with sum (PD)
US7 confirmed the importance of incorporating the tendon in the disease activity
assessment.
PMID- 29965854
TI - Effect of Uric Acid Control on Serum Creatinine.
AB - OBJECTIVE: Hyperuricemia has been epidemiologically associated with multiple
comorbidities including chronic renal failure and cardiovascular disease. Cause
and effect are difficult to address, given comorbidities associated with and
prevalence of metabolic syndrome. One impediment to achieving serum uric acid
(sUa) levels less than or equal to 6.0 mg/DL is the concept that allopurinol
might be nephrotoxic. We examined the relation of sUa less than or equal to 6.0
mg/dL to renal function over time. METHODS: This is a retrospective cohort study
of 348 hyperuricemia patients identified in 2015, as having been followed with
serial uric acid measurements. After 1 year of serial urate levels, to allow for
treatment, patient cohorts were defined: sUa less than or equal to 6.0 mg/dL and
sUa greater than 6.0 mg/dL. A repeated measure model was used to test for an
association between uric acid level and serum creatinine, while adjusting for
covariates. RESULTS: There was a significant difference in the least square means
of serum creatinine comparing those who achieved an sUa less than or equal to 6.0
mg/dL versus sUa greater than 6.0 mg/dL (1.39 mg/dL [95% confidence interval,
1.30-1.48] vs 1.57 mg/dL [95% confidence interval, 1.46-1.69]; P = 0.0015). This
is a between-group difference in creatinine of 0.18 mg/dL. If a change in serum
creatinine of 0.2 is considered significant, this short-term between-group
progression of renal failure approaches clinical significance. CONCLUSIONS: Given
that most serial measures were within the first few years of follow-up, and
change in renal function occurs slowly over time, the between group difference of
sUa of 0.18 mg/dL is close to a clinically significant creatinine difference of
0.2 mg/dL.
PMID- 29965855
TI - Quinacrine-Associated Punctate Palmar Keratoderma.
PMID- 29965856
TI - The diagnostic work-up of cancer-associated myositis.
AB - PURPOSE OF REVIEW: Despite the well-recognized association between malignancy and
myositis, definite data indicating the best strategy for diagnosing cancer in
myositis patients is lacking. In this article, we review the data on cancer
screening in patients with myositis, and propose an algorithm for this purpose
based on recently published data. RECENT FINDINGS: Evidence has recently emerged
supporting blind screening in patients with certain myositis phenotypes. In
addition to the clinical examination, imaging techniques such as PET/computed
tomography scanning and whole-body MRI, and determination of the autoantibody
profile beyond anti-TIF1gamma antibody, the well known cancer biomarker in
dermatomyositis, will help the clinician face this complex clinical situation.
Molecules related to the checkpoint inhibitor pathway, specifically soluble
programmed death 1, may also have a role in the diagnostic work-up of cancer in
myositis. In the future, blood tests analysing circulating DNA will certainly
help in detecting patients with cancer-associated myositis (CAM). SUMMARY: A step
forward has been achieved in the pathway to establish optimal cancer screening
for myositis patients. International consensus guidelines for an effective
diagnostic work-up of CAM are in progress and will be of paramount importance to
improving the outcome in these patients.
PMID- 29965857
TI - On media violence and aggression.
PMID- 29965858
TI - Autoimmune Myocarditis Caused by Immune Checkpoint Inhibitors Treated With
Antithymocyte Globulin.
AB - The immune checkpoint inhibitors have brought about a paradigm shift in the
treatment of many cancers and are being used as the first line therapy in
increasing number of aggressive malignancies, including metastatic melanoma.
Their adverse effects, mostly mediated by an uncontrolled overactivation of the
immune system, may compromise the therapeutic benefit. Combination immune
checkpoint therapies in particular, have higher therapeutic efficacy, but have
also been associated with a higher incidence of severe immune-related adverse
effects including autoimmune lymphocytic myocarditis. Recent clinical reports of
this rare and life threatening condition indicated rapid progression of severe
hemodynamic and electrical instability, with or without acute decompensated heart
failure, reduced ejection fraction and shock, pointing to the need for early
recognition, diagnosis and prompt management. Current guidelines for management
of other immune-related adverse effects recommend high-dose glucocorticoids, with
consideration of immunomodulators, such as infliximab in patients with severe
colitis. However, knowledge about the treatment approaches in immune-related
myocarditis remains extremely scarce. Here we report a case of severe, steroid
refractory, lymphocytic myocarditis that occurred after the first cycle of
combination immunotherapy with the programmed cell death protein-1 inhibitor,
nivolumab, and the cytotoxic T-lymphocyte-associated protein 4 blocker,
ipilimumab, for metastatic melanoma. We discuss treatment approaches including
the role for transvenous pacemaker, advanced heart failure support, and
interdisciplinary decision making.
PMID- 29965859
TI - Complete and Prolonged Response of Renal Cell Carcinoma With Rhabdoid Features to
Checkpoint Inhibitor Therapy.
AB - Checkpoint inhibitor immunotherapy has recently been proven to be an attractive
treatment option for a wide variety of malignancies. Nivolumab, an anti
programmed cell death protein-1 antibody, has been proven effective and safe in
treating metastatic renal cell carcinoma (RCC) with a clear cell component. We
report the case of a patient with high-grade clear cell RCC with rhabdoid
features who has achieved a durable complete response with nivolumab therapy
after multiple surgical interventions and progression on pazopanib. Genomic
evaluation in this case was characterized in part by a PBRM1 variant, similar to
the only other described case of RCC with rhabdoid features obtaining a complete
response to nivolumab. This case supports the potential utility of checkpoint
inhibitors in aggressive, rare subtypes of RCC where there are limited options
for therapy.
PMID- 29965860
TI - Renal sarcoidosis: approach to diagnosis and management.
AB - PURPOSE OF REVIEW: The purpose of this article is to provide understanding of
renal sarcoidosis, the different types of renal sarcoidosis, disease burden of
renal involvement, and treatment options. RECENT FINDINGS: The frequency of renal
involvement seems to be underestimated, but renal sarcoidosis represents a
relevant group of organ manifestations and significantly adds to the patient's
morbidity. Because histopathological analysis of renal biopsy specimens can
reveal various entities, a diagnostic workup is necessary in every patient with
sarcoidosis. SUMMARY: If systematically screened for renal manifestations are
likely to occur in up to 25-30% of all sarcoidosis patients. The most common
histological form of renal sarcoidosis is the granulomatous interstitial
nephritis; however, granulomas can be absent. Furthermore, one can find various
forms of secondary glomerulonephritis. In cases with dysregulated calcium
homeostasis, nephrocalcinosis and nephrolithiasis are commonly detectable kidney
diseases. AA amyloidosis or renal masses because of granuloma formation are
considered to be rare manifestations. In addition to glucocorticoids various
immunosuppressive treatments such as tumor necrosis factor alpha inhibitors have
proven to be effective based on case series.
PMID- 29965861
TI - Does 2-L Split-Dose Polyethylene Glycol Bowel Preparation Improve the Quality of
Screening Colonoscopy?
AB - Effectiveness of colonoscopy as a screening tool for colorectal cancer prevention
depends on the quality of bowel preparation. The type of bowel preparation agent
prescribed is largely dependent on the prescriber's preference, indicating a lack
of standard. A retrospective study (N = 84) compared the quality of bowel
preparation using 2-L split-dose polyethylene glycol prep (MoviPrep) to other
standard bowel preparations. Colonic mucosa visualized using the Boston Bowel
Preparation Scale, cecal intubation indicating successful completion of
colonoscopy, scope withdrawal time, and procedure duration were measured as
outcomes. Gastroenterologists from one academic practice prescribed 2-L split
dose bowel preparation (MoviPrep) (Group A) compared with Group B that did not
prescribe MoviPrep. Results of an independent t test between the 2 provider
groups demonstrated a statistically significant difference in colon visualization
based on Boston Bowel Preparation Score (t [40] = - 2.1, p = .035). Similar
statistically significant results were seen within Group A, which received 2-L
split-dose polyethylene glycol bowel preparation and other preparations (t [61] =
- 2.55, p = .013). All patients had successful completion of colonoscopy, with no
statistical difference in procedure duration and scope withdrawal time. Future
studies should confirm the benefits of 2-L split-dose polyethylene glycol
preparation for improved colon visualization during screening colonoscopy.
PMID- 29965862
TI - Descemet Stripping Automated Endothelial Keratoplasty With a Retention Suture:
Description of a Technique for Patients at High Risk of Graft Detachment.
AB - PURPOSE: To evaluate the utility, safety, and efficacy of a parallel or
cloverleaf retention suture in Descemet stripping automated endothelial
keratoplasty that does not penetrate donor tissue and can be removed at the slit
lamp for patients at high risk of graft detachment. METHODS: Data were
prospectively collected over 9 years from patients who received a retention
suture. Indications for use of a retention suture included difficulty with
postoperative positioning, abnormal intraocular anatomy including glaucoma tube
shunts, trabeculectomies, anterior chamber intraocular lens implants, previous
vitrectomy, aniridia, and aphakia, or history of previous graft detachment.
RESULTS: Of 128 surgeries, 12 (9.4%) required additional intervention for graft
reattachment (rebubble). Overall, 120 grafts (93.8%) remained clear and attached
either after surgery with a retention suture or after rebubble procedures. Mean
endothelial cell density at 1 year was 1840 cells/mm, and mean endothelial cell
density loss was 37.3%. CONCLUSIONS: A cloverleaf or parallel retention suture in
conjunction with Descemet stripping automated endothelial keratoplasty seems to
reduce the risk of detachment in high-risk patients, while maintaining adequate
cell density and graft clarity at 1 year.
PMID- 29965863
TI - Outcome of Human Donor Corneas Stored for More Than 4 Weeks.
AB - PURPOSE: Organ culture is the most common method for preservation of human donor
corneas within Europe, and the maximum accepted storage period is typically set
to 4 weeks. However, little is known about the fate of prolonged (4+ wks) organ
culture storage of donor corneas. The aim of this study was to evaluate the
clinical outcomes of corneal grafts preserved from 4 to 7 weeks compared with
corneal grafts preserved up to 4 weeks in organ culture medium. METHODS: A
registry study was performed, identifying 1252 corneal transplantations [Descemet
stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty
(PKP)] between February 2008 and November 2015 at Aarhus University Hospital,
Denmark. Data were extracted from The Danish Cornea Bank Registry and The Swedish
Cornea Registry, which also includes Danish patients. The outcomes evaluated, 2
years after transplantation, were graft function, rebubbling rates in DSAEK
surgeries, rejection rates, and endothelial cell density (ECD). RESULTS: A total
of 808 donor corneas were stored for <=29 days, with a mean preservation time
being 20 +/- 6 days (mean +/- SD, range: 6-29 days). A total of 444 donor corneas
were stored for >29 days, with a mean preservation time being 38 +/- 7 days (mean
+/- SD, range: 30-72 days). In both DSAEK (n = 835) and PKP (n = 417), no
statistically significant difference was observed in the frequency of graft
failure (DSAEK, P = 0.9 and PKP, P = 0.74), rebubbling rates (DSAEK P = 0.07),
rejection rates (DSAEK, P = 0.08 and PKP, P = 0.95), or ECD (DSAEK, P = 0.56 and
PKP, P = 0.44) between donor corneas cultured for <=29 days and donor corneas
cultured for >29 days. CONCLUSIONS: Corneas stored in organ culture for more than
4 weeks are equally suitable for DSAEK and PKP transplantation as corneas stored
in organ culture for up to 4 weeks.
PMID- 29965864
TI - Sensitivity to Melody, Rhythm, and Beat in Supporting Speech-in-Noise Perception
in Young Adults.
AB - OBJECTIVES: Musicians appear to have an enhanced ability to perceive speech-in
noise, prompting suggestions that musical training could be used to help people
who struggle to communicate in noisy environments. This study assessed the role
of sensitivity to beat, rhythm, and melody in supporting speech-in-noise
perception. DESIGN: This is an exploratory study based on correlation. The study
included 24 normally hearing young adult participants with a wide range of
musical training and experience. Formal and informal musical experience was
measured with the training subscale of the Goldsmiths' Musical Sophistication
Index. Speech reception thresholds (SRT) were measured using the Matrix Sentence
Test and three different speech-spectrum-shaped noise maskers: unmodulated and
sinusoidally amplitude-modulated (modulation frequency, fm = 8 Hz; modulation
depths: 60 and 80%). Primary predictors were measures of sensitivity to beat,
rhythm, and melody. Secondary predictors were pure-tone frequency discrimination
and auditory working memory (digit span). Any contributions from these two
predictors were to be controlled for as appropriate. RESULTS: Participants with
more musical experience and greater sensitivity to rhythm, beat, and melody had
better SRTs. Sensitivity to beat was more strongly linked with SRT than
sensitivity to either rhythm or melody. This relationship remained strong even
after factoring out contributions from frequency discrimination and auditory
working memory. CONCLUSIONS: Sensitivity to beat predicted SRTs in unmodulated
and modulated noise. We propose that this sensitivity maximizes benefit from
fluctuations in signal-to-noise ratio through temporal orienting of attention to
perceptually salient parts of the signal. Beat perception may be a good candidate
for targeted training aimed at enhancing speech perception when listening in
noise.This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
PMID- 29965865
TI - West Indies Glaucoma Laser Study (WIGLS)-2: Predictors of Selective Laser
Trabeculoplasty Efficacy in Afro-Caribbeans With Glaucoma.
AB - PURPOSE: To identify factors associated with intraocular pressure (IOP) reduction
following selective laser trabeculoplasty (SLT) in Afro-Caribbean people with
primary open-angle glaucoma (POAG). DESIGN: This was a prospective stepped-wedge
study. METHODS: Data were drawn from 72 Afro-Caribbean subjects with POAG
participating in the ongoing West Indies Glaucoma Laser Study. Multivariable
mixed-model analysis was utilized to develop a predictive model for percent IOP
reduction 12 months following SLT. Putative factors (age, sex, site, baseline
IOP, prior use of prostaglandin therapy, number of prewashout IOP-lowering
medications, central corneal thickness, severity of glaucoma, duration of follow
up, and signs of acute postoperative inflammation) were evaluated in bivariate
analysis. Factors significant at P<=0.2 were included in the final model. Right
and left eye data were modeled separately. RESULTS: At month 12 following SLT,
mean IOP reductions in the West Indies Glaucoma Laser Study were 6.2 to 6.5 mm Hg
(29.7% to 31.0%) in right and left eyes. The only factor significant in both eyes
(P=0.0005 in right eyes and P<0.0001 in left eyes) was time, with IOP reductions
being greatest at month 3 and declining slightly over time through month 12.
Vertical cup-disc ratio (P=0.006) and prior prostaglandin therapy (P=0.004) were
significant only in right eyes, and central corneal thickness (P=0.014) was
significant only in left eyes. Factors significant only unilaterally did not
approach significance in fellow eyes, suggesting the possibility that these
represent type 1 errors. Site (St. Lucia vs. Dominica) was not a significant
factor, establishing generalizability of these treatment outcomes to a broader
population of African-derived people. CONCLUSIONS: This analysis did not identify
any subject-specific factors consistently predictive of therapeutic response to
SLT. Of note, no factors predicted a suboptimal response. These findings
favorably position SLT for broad application as primary therapy in African
derived people with POAG.
PMID- 29965866
TI - Inner and Outer Retinal Contributions to Pupillary Light Response: Correlation to
Functional and Morphologic Parameters in Glaucoma.
AB - PURPOSE: To evaluate in patients with primary open-angle glaucoma (POAG) the
contribution of the inner and outer retinal photoreceptors to the pupillary light
responses (PLRs) correlated with both functional (color vision and visual field
perimetry) and morphologic (optical coherence tomography) parameters. METHODS: In
total, 45 patients with POAG and 25 healthy control participants were evaluated.
The PLR was measured as pupil diameter with an eye tracker; stimuli were
presented in a Ganzfeld. Pupil responses were measured monocularly, to 1 second
blue (470 nm) and red (640 nm) flashes with -3, -2, -1, 0, 1, 2, and 2.4 log cd/m
luminance levels. Color vision was evaluated with the Cambridge Color Test,
visual field was measured by standard automatic perimetry, and retinal nerve
fiber layer thickness was evaluated by optical coherence tomography. RESULTS:
Patients with moderate and severe POAG have a significantly decreased PLR that
depends on the severity of POAG, for both the 470 and 640 nm stimuli, revealing
the reduction of the contributions of the rods, cones, and intrinsically
photosensitive retinal ganglion cells to PLR. A significant loss of color
discrimination along the blue-yellow axis was observed in all stages of POAG.
Correlations among standard automatic perimetry, retinal nerve fiber layer
thickness, Cambridge Color Test, PLR, and melanopsin parameters were found.
CONCLUSIONS: The results provide evidence that in moderate and severe stages of
POAG, both the inner and outer retinal contributions to PLR are affected. Also, a
worsening in color vision was correlated with reduced PLR responses at high
intensity stimuli. These findings may enhance the clinical management of POAG
patients.
PMID- 29965867
TI - Pregnancy as a risk factor for thyroid cancer progression.
AB - PURPOSE OF REVIEW: The current review evaluates the impact of pregnancy on women
with thyroid cancer in three different clinical situations: those with newly
diagnosed differentiated thyroid cancer (DTC), those under active surveillance
for papillary thyroid microcarcinomas (PMCs), and those with previously treated
DTC. RECENT FINDINGS: Recent pregnancy is not associated with high-risk
pathological features of DTC. In women with known PMCs under active surveillance,
pregnancy does not increase the risk of disease progression. Thus, deferring
surgery for newly diagnosed DTC or known PMCs until after delivery is safe for
both mother and the unborn child. If a woman with previously treated DTC is
planning pregnancy, response-to-therapy status is an excellent guide for
predicting pregnancy-associated disease progression or recurrence. SUMMARY:
Clinical studies consistently show that pregnancy is not associated with
significant disease progression in newly diagnosed thyroid cancer, PMCs under
active surveillance, or previously treated DTC.
PMID- 29965868
TI - Myths and realities about alcohol and smoking in chronic pancreatitis.
AB - PURPOSE OF REVIEW: Alcohol and smoking play an important role in pancreatitis.
The present review will address the myths and evidences about alcohol and smoking
with pancreatitis to help improve the approach of healthcare professionals when
managing of these patients. RECENT FINDINGS: There is a growing recognition that
chronic pancreatitis is a multifactorial disease. Eliciting an accurate history
of alcohol consumption and smoking from patients, and if necessary, family
members, can help determine their contribution to the patient's disease. In the
absence of a convincing history, physicians should be open to consideration of
other etiologies. The amount and duration of alcohol consumption is the most
important determinant in increasing pancreatitis risk. Alcohol sensitizes the
pancreas to other insults or injury and promotes disease progression. Smoking is
an independent risk factor or chronic pancreatitis and has synergistic pathogenic
effects with alcohol. The natural history of chronic pancreatitis is highly
variable. A patient with alcoholic pancreatitis can have symptoms, recurrences or
exacerbations from disease-related complications or nonpancreatic causes. Novel
strategies are needed to enable patients quit smoking. SUMMARY: Obtaining
accurate history, appropriate evaluation and management can help to achieve
meaningful improvement in symptoms in patients with chronic pancreatitis.
Abstinence from alcohol and smoking cessation, when applicable, should be
recommended in all patients to prevent disease recurrences and progression.
PMID- 29965869
TI - Older adults use a prefrontal regulatory mechanism to reduce negative memory
vividness of a highly emotional real-world event.
AB - Previous research has revealed an age-related shift in how individuals recall
events from their personal past, with older adults reporting events that are more
positive than young adults. We recently showed that age-by-valence interactions
may be partially driven by a prefrontally mediated control mechanism recruited by
older adults during retrieval of negative laboratory events to reduce
phenomenological richness. Specifically, age was associated with greater
increases in prefrontal recruitment during retrieval of negative relative to
positive events, with this recruitment linked to decreases in hippocampal
activity and subjective vividness ratings. In the current study, we examined
whether older adults may rely on a similar mechanism during retrieval of a
complex, highly emotional real-world event. Participants (n=58, age: 18-87 years)
were presented with images related to the 2013 Boston Marathon Bombings and were
asked to retrieve a memory associated with each image. Images cued participants
with either negative (associated with fear, destruction, and sadness) or positive
(images of hope, resilience, support) features. This study replicated previous
episodic memory tasks: age was associated with more negative hippocampal
connectivity with dorsomedial prefrontal regions during retrieval of memories
triggered by negative relative to positive cues. Such findings suggest that older
adults may be recruiting a similar regulatory mechanism during retrieval of both
negative laboratory stimuli and highly negative events from their past. These
findings are discussed in relation to previous work showing that young and older
adults interact differently with the negative details related to a highly
negative event.
PMID- 29965870
TI - Influence of the intensity of galvanic vestibular stimulation and cutaneous
stimulation on the soleus H-reflex in healthy individuals.
AB - Modulation of the soleus H-reflex following galvanic vestibular stimulation (GVS)
has been used to evaluate vestibulospinal tract function. It is not known whether
this modulation is because of vestibular stimulation and/or cutaneous
stimulation, and the suitable stimulating intensity of GVS for the modulation is
not established. We investigated the influence of GVS intensity and cutaneous
stimulation on the soleus H-reflex in healthy adults. We applied cathodal GVS (at
1, 2, and 3 mA) or 3-mA cutaneous stimulation as a conditioning stimulation in a
random order to 17 individuals in the prone position with the head facing
forward, and we examined the changes in the right soleus H-reflex amplitude. We
maintained the interval between the conditioning stimulation's onset and the
tibial nerve stimulation evoking the soleus H-reflex constant at 100 ms. The
amplitude of all conditioned H-reflexes was significantly larger than that of the
unconditioned H-reflexes. The greatest facilitation of the H-reflex occurred when
3-mA GVS was applied. The degree of facilitation of the H-reflex by 3-mA GVS was
significantly larger than that produced by the 3-mA cutaneous stimulation. These
findings indicate that (a) the facilitation of the soleus motor neuron pool
excitability by GVS is derived from both vestibular stimulation and cutaneous
stimulation, and (b) the intensity of GVS affects the degree of facilitation.
When this technique is used to examine vestibulospinal tract function, no less
than 3 mA GVS may be appropriate as the conditioning stimulation.
PMID- 29965871
TI - A novel long noncoding RNA lnc158 promotes the differentiation of mouse neural
precursor cells into oligodendrocytes by targeting nuclear factor-IB.
AB - Long noncoding RNAs have been implicated in oligodendrocyte myelination and
oligodendrocyte maturation, but their roles in normal oligodendrocyte
differentiation are not fully defined. Here, we report a novel nonprotein-coding
RNA, named lnc158, discovered in mouse oligodendrocytes identified in
subependymal ventricular zone tissue by single-cell RNA sequencing. Lnc158 is an
endogenous antisense transcript of nuclear factor-IB (NFIB) and complementary to
3' untranslated region of NFIB mRNA. NFIB is a member of the nuclear factor-I
family and is essential in the development of many organs such as brains and
lungs. We found that lnc158 transcripts serve a biological function by regulating
the transcription level of the NFIB coding gene in neural stem cells.
Overexpression of lnc158 increased the expression of NFIB mRNA and knockdown of
lnc158 decreased the expression of NFIB mRNA, suggesting that NFIB is regulated
positively by lnc158. Further analyses showed that overexpression of lnc158 in
neural stem cells induced a modest increase in CNP, MBP, MAG, and OSP mRNA level,
and enhanced induction of differentiation along the lineage of oligodendrocytes.
These results together imply that lnc158 positively modulates the transcription
level of NFIB mRNA, leading to the enhanced induction of oligodendrocytes.
PMID- 29965872
TI - Voltage-dependent calcium channels in the neurosecretory cells of cerebral
ganglia of the mud crab, Scylla paramamosain.
AB - Voltage-dependent calcium channels (VDCCs) play a critical role in stimulus
secretion coupling in neurosecretory cells (NSCs). The crustacean cerebral
ganglion plays a crucial role in neuromodulation and controls neuropeptide
release. The present study used patch-clamp and Illumina sequencing techniques to
investigate the potential features of VDCC in the cerebral ganglia of the mud
crab (Scylla paramamosain). The electrophysiological characteristics of VDCC were
analyzed in three types of NSCs with a patch clamp. The thresholds for activation
of Ca channel current recorded from all the three types of NSCs were all above
40 mV, with peak amplitudes occurring around 0 mV. Therefore, it was concluded
that the currents recorded in NSCs were mediated by high-voltage-activated Ca
channels. Ca channel current densities in I type NSCs were significantly lower
than those in II and III type NSCs. Four VDCC subunits derived from three
transcripts were predicted from a transcriptome database of the cerebral ganglia.
Among these transcripts, Cavalpha1, Cavbeta, and Cavalpha2/delta were predicted
to encode 1674, 554, and 776 amino acids, respectively, and they shared
conservative domains with VDCC subunits in other species. Overall, these findings
provide an important basis for further studies on the neuroendocrine mechanisms
in crustaceans.
PMID- 29965873
TI - Molecular interplay between hyperactive mammalian target of rapamycin signaling
and Alzheimer's disease neuropathology in the NS-Pten knockout mouse model.
AB - Dysregulation of the PI3K/Akt/mTOR signaling cascade has been associated with the
pathology of neurodegenerative disorders, specifically Alzheimer's disease (AD).
Both in-vivo models and post-mortem brain samples of individuals with AD have
commonly shown hyperactivation of the pathway. In the present study, we examine
how neuron subset-specific deletion of Pten (NS-Pten) in mice, which presents
with hyperactive mammalian target of rapamycin (mTOR) activity, affects the
hippocampal protein levels of key neuropathological hallmarks of AD. We found NS
Pten knockout (KO) mice to have elevated levels of amyloid-beta, alpha-synuclein,
neurofilament-L, and pGSK3alpha in the hippocampal synaptosome compared with NS
Pten wild type mice. In contrast, there was a decreased expression of amyloid
precursor protein, tau, GSK3alpha, and GSK3beta in NS-Pten KO hippocampi.
Overall, there were significant alterations in levels of proteins associated with
AD pathology in NS-Pten KO mice. This study provides novel insight into how
altered mTOR signaling is linked to AD pathology, without the use of an in-vivo
AD model that already displays neuropathological hallmarks of the disease.
PMID- 29965874
TI - Unilateral whisker pad injection of botulinum toxin type a enhances spatial
learning in mice.
AB - The central cholinergic nervous system plays an important role in cognition, with
acetylcholine hypofunction considered to be a major factor of dementia. Botulinum
toxin type A (BoNT/A), a potent poison secreted by Clostridium botulinum, is used
widely for dystonia treatment and facial cosmesis. BoNT/A injection inhibits
acetylcholine release in the neuromuscular junction through cleavage of
synaptosomal-associated protein of 25 kDa in cholinergic terminals. Furthermore,
beyond the injection site, BoNT/A undergoes retrograde transport and transcytosis
to the central nervous system from peripheral cholinergic terminals. However,
whether peripheral BoNT/A injection affects the function of the central nervous
system and induces learning deficits remains unclear. We injected mice with
different doses of BoNT/A (2, 10, and 50 U/kg) or sterile saline (control) into
the left whisker pad to test spatial learning performance at different times
after injection using the Morris water maze. At 3 days and 4 weeks after
injection, the spatial learning ability of the control and BoNT/A-treated mice
showed no significant differences. Surprisingly, however, rather than spatial
learning impairment at 6 weeks after injection, BoNT/A-treated mice spent less
time than control mice in locating the experimental platform, indicating that
BoNT/A facial injection might promote spatial learning. Furthermore, our study
suggests that facial application of BoNT/A is safe and could play a positive role
in ameliorating the spatial learning deficits associated with neurodegenerative
diseases.
PMID- 29965876
TI - Cannabis Use, Psychotic Like Experiences and Aberrant Salience in a Sample of
Belgian Students.
AB - The main goal of our study was to investigate the association between psychotic
like experiences, aberrant salience, and cannabis use in a nonclinical sample of
Belgian students. The participants were asked to complete a self-report
questionnaire on cannabis use. The Community Assessment of Psychic Experiences
and the Aberrant Salience Inventory were used to assess psychotic-like
experiences and aberrant salience. The final sample was of 257 students. Cannabis
users showed significantly higher Aberrant Salience Inventory score and,
concerning the Community Assessment of Psychic Experiences, higher total,
positive, and negative dimension scores. Years of cannabis use and frequency of
use showed a positive correlation with Aberrant Salience Inventory score. Our
results support the evidence that cannabis use is associated with an increased
rate of psychotic experiences in individuals without a clinical form of
psychosis. Future studies are required to better investigate the meaning of the
association between cannabis use, psychotic-like experiences, and aberrant
salience.
PMID- 29965875
TI - Establishment of an induced pluripotent stem cell model of Hirschsrpung disease,
a congenital condition of the enteric nervous system, from a patient carrying a
novel RET mutation.
AB - Hirschsprung disease (HSCR) is a complex genetic disorder of the enteric nervous
system that is characterized by a complete loss of the neuronal ganglion cells in
the intestinal tract. It is one of the most frequent causes of congenital
intestinal obstruction and more than 80% of the causative mutations are in RET.
Here, we identified a new RET mutation in a patient and established a cell model
that can be used to elucidate the pathogenesis of HSCR. Peripheral blood was
collected from a patient who was clinically and pathologically diagnosed with
HSCR with a heterozygous deletion mutation (c.180delT; p.Glu61ArgfsX163) in exon
2 of RET. Patient-derived induced pluripotent stem cell (iPSC) lines were
generated from dermal fibroblasts. Using immunofluorescence staining and RT-PCR,
we showed that the generated iPSCs expressed the pluripotency markers OCT4,
SSEA4, SOX2, TRA-1-60, and NANOG. We also showed that the HSCR-iPSCs could
differentiate into cells from all three germ layers by spontaneous in-vitro
differentiation. In addition, 3 months after the administration of a subcutaneous
injection of these iPSCs into nude mice, teratomas with all three germ layers
were observed. We identified a new RET gene mutation causing HSCR and
successfully established a human iPSC line from an HSCR patient carrying this
novel RET mutation, which could be useful in pathogenesis studies of HSCR.
PMID- 29965877
TI - Incidence and Clinical Features of Panic Related Posttraumatic Stress.
AB - The current study assessed the incidence and associated features of posttraumatic
stress after the experience of panic. One hundred seventy-eight participants
meeting diagnostic criteria for panic attacks (PAs) were assessed using
standardized measures of posttraumatic symptoms and posttraumatic stress disorder
(PTSD) in specific reference to their experience of panic. Sixty-three (35.4%)
participants scored above the cutoff for PTSD in reference to the worst PA they
had experienced. Adjusted means for the four PTSD symptom clusters indicate that
panic-related posttraumatic symptoms are, on average, experienced "moderately" to
"quite a bit." Panic-related posttraumatic symptoms and PTSD were best predicted
by specific features of the panic experience itself, including subjective levels
of distress, fear of losing control, chest pain, agoraphobia, and number of PAs
experienced. These findings are discussed in terms of the diagnostic, prognostic,
and treatment implications for a subset of individuals presenting with panic who
may also have panic-related PTSD.
PMID- 29965878
TI - Before, During, and After Self Injury: The Practice Patterns of Nonsuicidal Self
Injury.
AB - Little is currently known about the repetitive behaviors that take place before,
during, and after nonsuicidal self-injury (NSSI). These practice patterns
surrounding repetitive self-injury may be part of a habituation process in NSSI.
Congruent with the opponent process theory (OPT), the mechanisms through which
NSSI is reinforced may include preparation, engagement, and follow-up practice
patterns to achieve the desired effect. This may result in increased habituation
leading to a change in method and resulting NSSI severity. College students with
a history of NSSI (N = 80) completed questionnaires, including an instrument to
assess practice patterns around NSSI. High levels of NSSI practice patterns were
positively related to various NSSI characteristics and clinical correlates,
suggesting higher levels of NSSI severity. Further, NSSI versatility partially
explained the relationship between NSSI practice patterns and habituation.
Consistent with OPT, practice patterns associated with repetitive NSSI may lead
an individual to change methods, fostering habituation to self-injury.
PMID- 29965879
TI - Treatment Within an Adult Mental Health Day Program: Examining Psychosocial
Outcomes.
AB - Day hospital programs provide stabilization, medication optimization, and
therapeutic intervention for individuals experiencing acute psychiatric
illnesses. The current study investigated treatment impact within an adult day
hospital setting in a large Canadian general acute care hospital. A total of 196
patients were sampled in a naturalistic design. Participants filled out measures
at admission and discharge, including the Patient Health Questionnaire-9, the
Generalized Anxiety Disorder-7, the World Health Organization Disability
Assessment Schedule 2.0, the Behavior and Symptom Identification Scale-24, the
Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, and the
Emotion Regulation Questionnaire (ERQ). Paired sample t-tests revealed
significant improvements from admission to discharge on all but one measure, the
ERQ Suppression scale. Overall, patients improved during treatment in terms of
psychopathology and disability, and perceived quality of life. When the emotion
regulation strategy of reappraisal was increasingly used over the duration of the
treatment, improvements were observed in symptomatology, quality of life, and
enhanced functionality. This article highlights the impact of therapeutic
interventions received within a Canadian day hospital program.
PMID- 29965880
TI - Nivolumab induced inflammation of seborrheic keratoses: a novel cutaneous
manifestation in a metastatic melanoma patient.
AB - Immune checkpoint inhibitors targeting the programmed cell death (PD)-1 receptor
have dramatically changed the landscape of metastatic melanoma treatment.
Nevertheless, these immuno-modulatory agents have associated side effects,
including dermatologic manifestations. To this end, we report a patient with
metastatic melanoma that was treated with a PD-1 inhibitor, and subsequently
developed inflammation of existing seborrheic keratosis lesions and new verrucous
keratoses, a cutaneous side effect that has not been previously reported to our
knowledge. The etiology of seborrheic and verrucous keratoses is not well
understood, although their physical and histopathologic similarities to chronic
viral-derived lesions, such as human papilloma virus, suggest a potential viral
association. Chronic viral infections are known to result in T-cell tolerance
because of persistent antigen stimulation. PD-1 inhibition is able to
reinvigorate exhausted T cells, which are accordingly able to decrease viral
load. Thus, the inflammatory reaction, seen in our patient, may be the result of
PD-1 inhibition reactivating virally driven T lymphocytes.
PMID- 29965881
TI - Combination of cytokine-directed and anti-programmed cell death protein 1 therapy
- a new attractive option in melanoma treatment?
AB - The use of monoclonal antibodies against programmed cell death protein 1 (anti-PD
1) has markedly transformed the management of melanoma. However, only a minority
of patients treated with anti-PD-1 therapy show a response to therapy and some of
them develop immune-related adverse events that can be managed with steroids or
anticytokine therapy. A recent study published in Nature Communications has
reported that treatment with anti-PD-1 in a tumor necrosis factor-deficient
environment may lead to higher response rates to immunotherapy by reducing tumor
infiltrating lymphocytes death, accumulating dendritic cells within cancer, and
downregulating T-cell immunoglobulin and mucin-domain-containing-3 expression.
This research provides the first proof-of-concept of combining immunotherapy and
anti-tumour necrosis factor-alpha in the melanoma treatment.
PMID- 29965882
TI - Pharmacokinetics and Pharmacodynamics of Once-Daily Tacrolimus Compared With
Twice-Daily Tacrolimus in the Early Stage After Living Donor Liver
Transplantation.
AB - BACKGROUND: This study investigates the pharmacokinetics and pharmacodynamics of
tacrolimus using the once-daily (OD) formulation in the early stage after living
donor liver transplantation (LDLT) in comparison with those using the twice-daily
(TD) formulation. METHODS: Nine patients undergoing primary LDLT and treated with
the OD tacrolimus formulation were included. The trough blood concentration (C0)
of tacrolimus was monitored every day for 3 weeks after LDLT. A time course study
of the blood tacrolimus concentrations and calcineurin (CN) phosphatase activity
in peripheral blood mononuclear cells was performed 3 weeks after LDLT.
Pharmacokinetic and pharmacodynamic parameters were compared with previously
reported data using the TD formulation. RESULTS: The interindividual variability
in the daily dose of tacrolimus was significantly larger in the OD formulation
than in the TD formulation (P < 0.001). In the time course study, the tacrolimus
blood concentrations at 4, 8, and 12 hours after administration and the area
under the concentration-time curve from 0 to 24 hours (AUC0-24) in the OD group
were significantly higher than in the TD group, although the C0 was equivalent.
In addition, the C0 was not significantly correlated with the AUC0-24 in the OD
formulation. The apparent clearance and the pharmacodynamic parameters examined
were not significantly different between the OD and TD groups. CONCLUSIONS: The
C0 monitoring of the OD formulation may not be optimal in patients at the early
stage after LDLT because the C0 was not correlated with the AUC0-24. If
clinicians target the same C0 using the OD and TD formulations, the exposure of
tacrolimus can be higher in the OD formulation, and excessive immunosuppression
should be noted. Particular attention should be paid to the patients in the early
stage after LDLT in the use of the OD oral formulation of tacrolimus.
PMID- 29965883
TI - Influence of Sex, Age, and Weight on Levetiracetam Pharmacokinetics.
AB - BACKGROUND: Levetiracetam (LEV) is a second-generation antiepileptic drug
extensively used in therapeutics. The aim of this study was to evaluate the
influence that sex, age, and weight exert on LEV pharmacokinetics in clinical
practice. METHODS: We conducted a 6-year retrospective observational study.
Patients were classified in subgroups according to sex, weight (normal range,
overweight, and obese), and age (young adult: 16-30 years old, middle-aged adult:
31-50 years old, advanced adult: 51-64 years old, and elderly adult: >=65 years
old). We compared LEV apparent oral clearance (LEV CL/F) between the subgroups.
RESULTS: A total of 238 LEV basal serum concentrations (LEV C0) corresponding to
156 patients were identified. Significant differences were observed in LEV CL/F
between males and females when LEV CL/F was expressed as L/h [mean (SD): 4.79
(1.84) L/h in males versus 4.13 (1.64) L/h in females; P < 0.001]. These
differences were not significant when LEV CL/F was normalized by weight [mean
(SD): 60.64 (24.90) mL/h/kg in males versus 64.10 (28.87) mL/h/kg in females;
n.s.]. Weight in females was 17% lower compared with males. A progressive
reduction in LEV CL/F was observed with increasing age, in a proportion that was
similar to the decline in renal function. The elderly patients presented 30%
lower LEV CL/F (mL/h/kg) and 43% lower creatinine clearance (CCr) in comparison
with adults. No statistically significant differences were observed in LEV CL/F
calculated in L/h between weight subgroups. However, when LEV CL/F was expressed
in mL/h/kg, a progressive reduction was observed [normal weight: 72.21 (28.97);
overweight: 57.84 (25.38); obese: 49.45 (14.50); P < 0.001]. A significant and
positive correlation between CCr and LEV CL/F was observed, confirming the
important role of the renal function in LEV CL/F. The CCr increased in each sex
group when weight increased; however, LEV CL/F (L/h) remained constant.
CONCLUSIONS: Sex, age, and weight affect LEV pharmacokinetics, having an impact
on the individual dosage regimen needed to achieve the therapeutic objective. Sex
is a conditioning factor of LEV CL/F, although its influence is principally due
to the weight. LEV CL/F decreases with advancing age, proportionally to the
decline in renal function. It is confirmed that LEV dosage per body weight is not
required, and prescribing higher doses of LEV in obese patients is not justified.
These data suggest that routine LEV therapeutic drug monitoring in the elderly
patients, patients with renal dysfunction, and obese patients is indicated.
PMID- 29965884
TI - Loss of CD31 receptor in CD4+ and CD8+ T-cell subsets in children with primary
hypertension is associated with hypertension severity and hypertensive target
organ damage.
AB - BACKGROUND: Primary hypertension is associated with still poorly known T-cell
dependent immunity defects that participate in the disease development. However,
the relationship between peripheral T-cell subset distribution and disease
severity in humans is not known. The aim of the study was to find out if target
organ damage in adolescents with primary hypertension is associated with thymus
dependent lymphocytes renewal reflected by changes in the T-cell subset phenotype
characteristics. METHODS: Using seven-color flow cytometry technique, we assessed
CD31, CCR7 and CD28 receptors expression in CD45RA and CD45RO bearing peripheral
CD4 and CD8 T-cell subsets. The study included 32 hypertensive
children/adolescents and 35 sex-matched and age-matched controls. RESULTS:
Children with primary hypertension had slightly increased CD4 T-cell pool but
decreased population of CD31 expressing CD4 T-cell subsets (recent thymic
emigrants). Frequency of the CD4 and CD4/CD45RA+ T cells lacking CD31 correlated
positively with the hypertensive organ damage markers (pulse wave velocity,
central blood pressure, left ventricular mass index). Left ventricular
hypertrophy was associated with decreased CD4/CD45RA:CD4/CD45RO ratio, loss of
the CD31 receptor in the CD4 and CD8 T-cell subsets and increased population of
effector/memory T cells bearing CD8/CD28 and CD8/CD45RA+/CCR7 phenotype.
Regression analysis revealed that these associations were independent of age,
sex, and BMI. CONCLUSION: The results suggest that subclinical arterial injury
and left ventricular hypertrophy in adolescents with primary hypertension is
associated with declined thymic function and increased pool of T cells bearing
effector/memory phenotype.
PMID- 29965885
TI - Risk of new-onset metabolic syndrome associated with white-coat and masked
hypertension: data from a general population.
AB - AIM: In the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study,
clinical and metabolic variables as well as office, home and ambulatory blood
pressure (BP) values were simultaneously measured at baseline and after a 10-year
follow-up. The study design allowed us to assess the value of selective and
combined elevation of different BP phenotypes in predicting new-onset metabolic
syndrome (MetS). METHODS: The present analysis included 1182 participants without
MetS at baseline, as defined by the APT III criteria. On the basis of office, 24
h ambulatory BP and home values, participants were divided into four groups:
normal, white-coat hypertension (WCH), masked hypertension and sustained
hypertension. RESULTS: Compared with participants with in-office and out-of
office normal BP, a greater incidence of new-onset age-adjusted and sex-adjusted
MetS was observed in WCH (OR = 1.75, CI 1.01-3.04, P = 0.0046), masked
hypertension (OR = 2.58, CI 1.26-5.30; P = 0.009) and sustained hypertension (OR
= 2.14, CI 1.20-3.79, P = 0.009)) when out-of-office BP was defined by ambulatory
criteria. This was not the case when out-of-office BP was defined by home
criteria, as only the WCH group showed a greater risk (OR 2.16, CI 1.28-3.63, P =
0.003). Similar findings were obtained for single components of the MetS such as
abdominal obesity and hyperglycemia. CONCLUSION: Our study provides evidence that
either isolated or combined BP elevations identified by office/ambulatory
measurements, carry an increased risk of new-onset MetS, whereas, only WCH is
associated with a greater risk of incident MetS whenever BP phenotypes are
identified by office/home measurements. In a clinical perspective, a
comprehensive evaluation of BP status based on office/ambulatory measurements may
improve diagnosis of new-onset MetS and activate measures for its prevention.
PMID- 29965886
TI - Quantitative Risk Factor Analysis of Post-Operative Dysphagia After Anterior
Cervical Discectomy and Fusion (ACDF) using the Eating Assessment Tool-10 (EAT
10).
AB - STUDY DESIGN: Retrospective case series. OBJECTIVE: To utilize the Eating
Assessment Tool-10 (EAT-10) to quantitatively analyze risk factors contributing
to dysphagia after ACDF. SUMMARY OF BACKGROUND DATA: Anterior cervical discetomy
and fusion is one of the most common procedures performed in the United States
with post-operative dysphagia rates ranging from 2%-60%. The EAT-10 is a self
administered, symptom-specific 10-item clinical instrument to document dysphagia
symptom severity and has demonstrated excellent internal consistency, test-retest
reliability, and criterion-based validity. METHODS: This study utilized a
retrospective chart review of 163 patients from July 2013 to October 2017 who
underwent ACDF at a single institution and prospectively completed EAT-10 surveys
pre- and post-operatively. EAT-10 scores were collected preoperatively and at
postoperative day 1, day 14, 1 month, 3 month, 6 months, and 12 months.
Preselected risk factors were abstracted from the patients' chart. Univariate
analyses was performed to identify candidate variables that correlated with
abnormal EAT-10 scores at each time point. Multivariate logistic regression was
then utilized to identify risk factors that were independently correlated with
abnormal EAT-10 scores at each time point. RESULTS: Female gender, younger
patients and increased OR time was associated with increased rates of dysphagia
in the early postoperative period. History of obstructive sleep apnea, history of
asthma, increased ASA score and a larger number of spinal levels included in the
surgery were correlated with increased dysphagia in the later postoperative
periods. CONCLUSION: Dysphagia is common following ACDF. Factors associated with
longer term dysphagia seem to be more associated with pre-existing medical
comorbidities. Understanding risk factors that correlate with increased rates of
dysphagia has the potential to improve preoperative patient counseling and
changes in operative management. LEVEL OF EVIDENCE: 4.
PMID- 29965887
TI - MULTIMODAL IMAGING OF FOCAL CHOROIDAL EXCAVATION COMPLICATED BY CHOROIDAL
NEOVASCULARIZATION IN A PATIENT WITH ANGIOID STREAKS AND PSEUDOXANTHOMA
ELASTICUM.
AB - PURPOSE: To describe a case of focal choroidal excavation (FCE) complicated with
Type-2 choroidal neovascularization (CNV) in a patient with angioid streaks
secondary to pseudoxanthoma elasticum before and after treatment with
bevacizumab. METHODS: Fundus photography, fundus autofluorescence, fluorescein
angiography, indocyanine green angiography, spectral-domain optical coherence
tomography (SD-OCT) and SD-OCT angiography were performed in a 60-year-old white
woman with angioid streaks and bilateral FCE. Spectral domain OCT images were
taken before and after three-monthly intravitreal injections of bevacizumab.
Histopathological analysis of the dermis established the diagnosis of
pseudoxanthoma elasticum. RESULTS: Multimodal imaging revealed bilateral FCE and
CNV. Spectral domain OCT diagnosed bilateral FCE and Type-1 and Type-2 CNV in the
right eye, and irregular vascular network, along macular streak, in both eyes,
which were not observed on fluorescein neither on indocyanine green angiography,
but only on SD-OCT angiography. Patient presented good anatomical and functional
response to intravitreal injections of bevacizumab. CONCLUSION: Focal choroidal
excavation is a rare condition detected mainly by SD-OCT, which may be associated
with angioid streaks secondary to pseudoxanthoma elasticum and complicated by
CNV. Multimodal imaging is important for diagnosis and follow-up of such
patients, even in the absence of signs of CNV, and anatomical and functional
response to anti-vascular endothelial growth factor therapy is good.
PMID- 29965888
TI - Factors Associated With Mortality in Children Who Successfully Wean From
Extracorporeal Membrane Oxygenation.
AB - OBJECTIVES: Extracorporeal membrane oxygenation is an established therapy for
cardiac and respiratory failure unresponsive to usual care. Extracorporeal
membrane oxygenation mortality remains high, with ongoing risk of death even
after successful decannulation. We describe occurrence and factors associated
with mortality in children weaned from extracorporeal membrane oxygenation.
DESIGN: Retrospective cohort study. SETTING: Two hundred five extracorporeal
membrane oxygenation centers reporting to the Extracorporeal Life Support
Organization. SUBJECTS: Eleven thousand ninety-six patients, less than 18 years,
supported with extracorporeal membrane oxygenation during 2007-2013, who achieved
organ recovery before decannulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: Primary outcome was hospital mortality less than or equal to 30 days
post extracorporeal membrane oxygenation decannulation. Among 11,096 patients,
indication for extracorporeal membrane oxygenation cannulation was respiratory
(6,206; 56%), cardiac (3,663; 33%), or cardiac arrest (extracorporeal
cardiopulmonary resuscitation, 1,227; 11%); the majority were supported with
venoarterial extracorporeal membrane oxygenation at some stage in their course
(8,576 patients; 77%). Mortality was 13%. Factors associated with mortality
included younger age (all < 1 yr categories compared with older, p < 0.05), lower
weight among neonates (<= 3 vs > 3 kg; p < 0.001), mode of extracorporeal
membrane oxygenation support (venoarterial extracorporeal membrane oxygenation
compared with venovenous extracorporeal membrane oxygenation, p < 0.001), longer
admission to extracorporeal membrane oxygenation cannulation time (>= 28 vs < 28
hr; p < 0.001), cardiac and extracorporeal cardiopulmonary resuscitation compared
with respiratory extracorporeal membrane oxygenation (both p < 0.001),
extracorporeal membrane oxygenation duration greater than or equal to 135 hours
(p < 0.001), preextracorporeal membrane oxygenation hypoxemia (PO2 <= 43 vs > 43
mm Hg; p < 0.001), preextracorporeal membrane oxygenation acidemia (p < 0.001),
and extracorporeal membrane oxygenation complications, particularly cerebral or
renal (both p < 0.001). CONCLUSIONS: Despite extracorporeal membrane oxygenation
decannulation for organ recovery, 13% of patients die in hospital. Mortality is
associated with patient factors, preextracorporeal membrane oxygenation illness
severity, and extracorporeal membrane oxygenation management. Evidence-based
strategies to optimize readiness for extracorporeal membrane oxygenation
decannulation and postextracorporeal membrane oxygenation decannulation care are
needed.
PMID- 29965889
TI - Catheter-assisted 360-Degree Trabeculotomy for Congenital Glaucoma.
AB - PURPOSE: To determine feasibility, efficacy, and safety of ab externo 360-degree
trabeculotomy with illuminated microcatheter for congenital glaucoma. PATIENTS
AND METHODS: The postoperative results of 36 eyes in 23 consecutive patients who
underwent 360-degree trabeculotomy for primary congenital glaucoma (PCG) or
secondary congenital glaucoma using an illuminated microcatheter were
retrospectively analyzed. Success criteria were defined as intraocular pressure
(IOP) <=18 mm Hg without (complete success) and with medication (qualified
success). RESULTS: In all previously nonoperated eyes with PCG (group 1), the
Schlemm's canal was identified and circumferentially cannulated for 360-degree
trabeculotomy. In group 2 comprising of operated eyes with PCG and eyes with
secondary congenital glaucoma, the performance of 360-degree trabeculotomy failed
in 4 eyes because of the Schlemm's canal occlusion or high tissue resistance of
the trabecular meshwork. Mean preoperative IOP was 28.6+/-5 and 29.6+/-9 mm Hg
with 7 of 20 eyes and 7 of 9 eyes receiving IOP-lowering medication in group 1
and group 2, respectively. Mean postoperative IOP was reduced to 13+/-2.7 and
20.2+/-7.1 mm Hg after a mean follow-up of 15.3 and 12.7 months with 4 of 20 eyes
and 5 of 9 eyes receiving medication in group 1 and group 2, respectively. Four
eyes underwent further surgery. Complete success was achieved in 16 and 3 eyes,
whereas qualified success was achieved in 20 and 4 eyes from group 1 and group 2,
respectively. In all eyes, a mild to moderate postoperative hyphema was observed.
CONCLUSIONS: Ab externo catheter-assisted 360-degree trabeculotomy controls IOP
in a majority of patients with congenital glaucoma after a single operation.
Moderate blood reflux in the anterior chamber is considered as a common
postoperative finding. We did not observe hypotony or other severe complications
in our series. In 1 patient, we experienced catheter misdirection in an eye that
had previously undergone trabeculotomy.
PMID- 29965890
TI - Longitudinal Changes in Bleb Height, Vascularity, and Conjunctival Microcysts
After Trabeculectomy.
AB - OBJECTIVE: The objective of this article was to study longitudinal changes in
bleb morphology (presence of microcysts and bleb height and vascularity) in
subjects enrolled in the Singapore 5-Fluorouracil (5-FU) trabeculectomy study.
STUDY DESIGN: Retrospective subgroup analysis of a randomized controlled trial.
MATERIALS AND METHODS: Following trabeculectomy with either 5-FU or placebo,
subjects were reviewed at day 1, weeks 1, 2, and 3, and months 3, 6, 9, 12, 16,
20, 24, 28, 32, and 36 and intraocular pressure (IOP), presence of microcysts and
bleb height and vascularity graded and recorded. Statistical analyses were used
to investigate baseline factors (demographics, eye drops use, IOP, treatment
type, and comorbidities) that might account for long-term bleb changes and assess
the influence of bleb morphology on mean, maximum, minimum, and variation in IOP
following trabeculectomy. RESULTS: One hundred fifty-nine (61.2%) subjects
completed follow-up and 71 subjects (44.7%) received 5-FU. Proportion of subjects
with microcysts increased posttrabeculectomy till weeks 3 and 6 in 5-FU and
placebo-treated eyes, respectively, before decreasing. Presence of microcysts at
day 1 and week 2 was associated with lower mean (P=0.027 to 0.033), maximum
(P=0.040), and minimum IOP (P=0.010). Mean bleb height decreased over 36 months
and at months 20 and 36 was associated with maximum (P=0.031) and minimum IOP
(P=0.032), respectively. Mean bleb vascularity decreased till month 9 and
remained fairly constant after. CONCLUSIONS: Microcysts seen early
posttrabeculectomy is associated with lower IOP. Blebs reduce in height as they
remodel and the relationship between bleb vascularity and IOP is complex.
PMID- 29965891
TI - Histopathologic Examination of Trabecular Meshwork Changes After Trabecular
Bypass Stent Implantation.
AB - PURPOSE: The purpose of this article was to evaluate how human trabecular
meshwork (TM) is influenced by the chronic presence of trabecular bypass
implants. METHODS: Human TM samples were obtained intraoperatively from 3
patients who had previously undergone implantation of a trabecular micro-bypass
stent. Trabecular strips were obtained with a goniotomy blade from areas directly
adjacent to the stent after stent removal. Tissue samples were preserved,
processed, cut, and stained according to standardized laboratory protocol.
Harvested samples were compared with human cadaveric TM from an eye without
ocular disease as well as TM obtained from a glaucomatous eye without prior stent
placement. RESULTS: In all samples, a significant increase in the amount of
fibrous material compared with cellular material was noted when compared with
controls. In a single strip, a basement membrane-like structure was noted, which
correlated with a semiopaque membrane noted intraoperatively overlying the stent
and adjacent TM. Further, TM cells were absent from areas adjacent to the stent
implantation site with related collapse of collagen beams. CONCLUSIONS: These
findings indicate that inflammatory and fibrotic changes are present surrounding
the device with clear differences noted when compared with both healthy and
glaucomatous controls. These changes suggest a possible etiology for device
failure over time. Further studies are necessary to tease out differences in TM
tissue reaction to various implant materials as well as to make comparisons to
procedures that excise TM.
PMID- 29965892
TI - Reversible Cystoid Macular Edema Following Uneventful Microinvasive Kahook Dual
Blade Goniotomy in a Pseudophakic Patient: A Case Report.
AB - PURPOSE: The purpose of this study is to present a case of cystoid macular edema
(CME) as a potential complication following uncomplicated stand-alone Kahook Dual
Blade (KDB) goniotomy in a patient with pseudoexfoliative glaucoma. METHODS: A 71
year-old woman who developed CME following KDB goniotomy subsequently treated
with topical nonsteroidal anti-inflammatory (NSAID) therapy. RESULTS: The CME
successfully regressed following a standard course of topical NSAID therapy.
CONCLUSIONS: This case report describes the first case of CME following
uneventful stand-alone KDB goniotomy and highlights the importance of
postoperative topical NSAID therapy with regard to both prophylaxis and
treatment.
PMID- 29965893
TI - The Amount of Proximal Lumbar Lordosis Is Related to Pelvic Incidence.
AB - BACKGROUND: Given that the pelvis is the pedestal on which the spine lies, its
morphology has been observed to be associated with specific sagittal spinal
shapes and should therefore be taken into account when dealing with pathologic
conditions of the spine. However, the exact relationship between the pelvic
morphology and lumbar lordosis still remains poorly defined. We hypothesized that
the shape of the lumbar lordosis and its relationship with the pelvis could be
described using anatomic parameters, independently of posture.
QUESTIONS/PURPOSES: (1) What is the variation of lumbar segmental lordosis in an
asymptomatic adult population? (2) Is there an association between increasing
magnitude of pelvic incidence (PI) and segmental lordosis? (3) How does the
position of the apex of lordosis change with increasing magnitude of PI value?
METHODS: This retrospective study used data drawn from a longitudinally
maintained database; between March 2014 and January 2015, 119 asymptomatic
volunteers between 18 and 79 years old were enrolled in the study. Mean age was
51 years; there were 81 women and 38 men. Both segmental and cumulative lordosis
were measured and used to describe the shape of the lumbar spine. We defined
cumulative lordosis as the angle between L1 and S1, proximal lordosis as the
angle between L1 and the superior endplate of L4, and distal lordosis as the
angle between the superior endplates of L4 and S1. PI is defined as the angle
between the line passing through the center of the femoral head and the center of
the sacral endplate and a line perpendicular to the sacral endplate. Pearson's
correlation was performed to analyze the relationship among PI, proximal and
distal lordosis. Stratification by PI was performed (low, < 45 degrees ; average,
45 degrees -60 degrees ; and high, > 60 degrees ) and the proportions of distal
and proximal lordosis were then compared using an analysis of variance test.
RESULTS: In the whole cohort, proximal lordosis accounted for 38% of total
lordosis, whereas distal lordosis accounted for 62%. PI revealed a positive
correlation with proximal lordosis (r = 0.546; p < 0.001). However, there was no
correlation with distal lordosis (r = 0.087; p = 0.346). Stratification by PI
showed that proximal lordosis increased across PI groups (16.6 degrees [+/- 10]
versus 21.6 degrees [+/- 9] versus 30.1 degrees [+/- 9]; p < 0.001), whereas
distal lordosis remained relatively constant (34.8 degrees [+/- 8] versus 36.7
degrees [+/- 7] versus 35.9 degrees [+/- 10]; p = 0.581). Apex position was
overall more proximal as PI increased (r = -0.199; p = 0.034). CONCLUSIONS: Our
study demonstrated that PI influences only the proximal part of the lordosis, but
not the distal part in an asymptomatic adult population. The proximal part of the
lumbar spine had the most variability across individuals and appeared to
accommodate to pelvic morphology (incidence). Further studies using a larger
cohort size are encouraged not only to refine this relationship, but also to
investigate the effect of restoration of normal lordotic shape of the lumbar
spine on the functional outcomes after spinal fusion. CLINICAL RELEVANCE: Our
findings may be useful for surgical planning in an era of patient-specific care.
The findings suggest that surgeons should aim for a patient-specific lumbar shape
rather than simple global lordosis matched to the PI.
PMID- 29965894
TI - Patient Perceptions Correlate Weakly With Observed Patient Involvement in
Decision-making in Orthopaedic Surgery.
AB - BACKGROUND: Shared decision-making between patients and physicians involves
educating the patient, providing options, eliciting patient preferences, and
reaching agreement on a decision. There are different ways to measure shared
decision-making, including patient involvement, but there is no consensus on the
best approach. In other fields, there have been varying relationships between
patient-perceived involvement and observed patient involvement in shared decision
making. The relationship between observed and patient-perceived patient
involvement in decision-making has not been studied in orthopaedic surgery.
QUESTIONS/PURPOSES: (1) Does patient-perceived involvement correlate with
observed measurements of patient involvement in decision-making in orthopaedic
surgery? (2) Are patient demographics associated with perceived and observed
measurements of patient involvement in decision-making? METHODS: We performed a
prospective, observational study to compare observed and perceived patient
involvement in new patient consultations for eight orthopaedic surgeons in
subspecialties including hand/upper extremity, total joint arthroplasty, spine,
sports, trauma, foot and ankle, and tumor. We enrolled 117 English-literate
patients 18 years or older over an enrollment period of 2 months. A member of the
research team assessed observed patient involvement during a consultation with
the Observing Patient Involvement in Decision-Making (OPTION) instrument (scaled
1-100 with higher scores representing greater involvement). After the
consultation, we asked patients to complete a questionnaire with demographic
information including age, sex, race, education, income, marital status,
employment status, and injury type. Patients also completed the Perceived
Involvement in Care Scale (PICS), which measures patient-perceived involvement
(scaled 1-13 with higher scores representing greater involvement). Both
instruments are validated in multiple studies in various specialties and the
physicians were blinded to the instruments used. We assessed the correlation
between observed and patient-perceived involvement as well as tested the
association between patient demographics and patient involvement scores. RESULTS:
There was weak correlation between observed involvement (OPTION) and patient
perceived involvement (PICS) (r = 0.37, p < 0.01) in decision-making (mean
OPTION, 28.7, SD 7.7; mean PICS, 8.43, SD 2.3). We found a low degree of observed
patient involvement despite a moderate to high degree of perceived involvement.
No patient demographic factor had a significant association with patient
involvement. CONCLUSIONS: Further work is needed to identify the best method for
evaluating patient involvement in decision-making in the setting of discordance
between observed and patient-perceived measurements. Knowing whether it is
necessary for (1) actual observable patient involvement to occur; or (2) a
patient to simply believe they are involved in their care can inform physicians
on the best way to improve shared decision-making in their practice. LEVEL OF
EVIDENCE: Level II, therapeutic study.
PMID- 29965895
TI - Pearls: How to Use Subchondral Pin Assisted Reduction to Restore Alignment of
Distal Radius Fractures.
PMID- 29965896
TI - Management After Percutaneous Cholecystostomy: What Should We do With the
Catheter?
AB - BACKGROUND: Percutaneous cholecystostomy (PC) is an alternative to
cholecystectomy for acute calculous cholecystitis (ACC) in patients with high
mortality risk, but the catheters' and patients' management remains unclear. This
study aimed to determine outcomes after PC and to define surgical strategy.
METHODS: All patients who underwent PC between 2009 and 2014 for ACC in a single
institution were reviewed for outcomes and postdrainage management. RESULTS:
Forty-one patients underwent PC with a median age of 77 years. Twenty patients
(45%) presented American Society of Anesthesiologists (ASA) score 3-4, and all
had cholecystitis grade II or III. The 6-month mortality was 17% (7/41 patients).
Twelve patients (29%) presented PC-related complications. Catheters were removed,
clamped, left open, and dislodged for 17, 9, 5, and 5 patients, respectively.
Three patients died after PC, and data were missing for 2 patients. Twenty-five
(61%) patients underwent cholecystectomy after PC, and were significantly younger
(median age, 70 vs. 83; P<0.010), and presented with higher ASA score (ASA: 3-4,
36% vs. 68%; P=0.041) and more grade III cholecystitis (16% vs. 44%; P=0.050).
Among 16 patients who did not undergo cholecystectomy, none presented recurrent
gallstone disease (median survival, 7 mo; range, 0 to 55). CONCLUSIONS: The risk
of complications associated with the catheter is high. To prevent morbidity
related to PC, we suggest removing the catheter when ACC is controlled.
PMID- 29965897
TI - Genetics of Exfoliation Syndrome.
AB - Exfoliation syndrome (XFS) is an age-related systemic disorder of the
extracellular matrix with important ocular manifestations. In this disorder,
exfoliation material (XFM) is deposited in the anterior chamber of the eye on the
lens, iris, ciliary body, as well as other intraocular structures. This
accumulation of XFM can obstruct the trabecular meshwork, resulting in elevated
intraocular pressure and eventually causing glaucomatous optic neuropathy. In
itself a highly hereditable condition, XFS is also the commonest recognizable
cause of open-angle glaucoma worldwide, accounting for a majority of cases in
some countries. Outside the eye, XFM deposits around blood vessels, particularly
in association with elastic connective tissue, are found in numerous organs,
including the skin, heart, and lungs. Long suspected to be a genetic disorder on
the basis of familial aggregation studies, recent genome-wide association studies
uncovered strong association between 7 genetic loci (LOXL1, CACNA1A, FLT1-POMP,
TMEM136-ARHGEF12, AGPAT1, RBMS3, and SEMA6A) and increased risk of XFS. At the
same time, a lower than usual sibling relative risk for XFS compared with other
inherited conditions suggests XFS to be a complex disorder. The evidence to date
suggests that additional genetic loci and biological insights for XFS remain to
be identified through larger studies.
PMID- 29965898
TI - LOXL1 Polymorphisms: Genetic Biomarkers that Presage Environmental Determinants
of Exfoliation Syndrome.
AB - An agnostic high throughput search of the genome revealed a robust association
between LOXL1 genetic polymorphisms and exfoliation syndrome (XFS), a discovery
that likely would not have been possible with candidate or family-based gene
search strategies. While questions remain regarding how LOXL1 gene variants
contribute to XFS pathogenesis, it is clear that the frequencies of disease
related alleles do not track with the varying disease burden throughout the
world, prompting a search for environmental risk factors. A geo-medicine approach
revealed that disease load seemed to increase as a function of the distance from
the equator. The exact reason for this extraequatorial disease distribution
pattern remains unclear, but a greater amount of time spent outdoors is a robust
risk factor for XFS, suggesting climatic factors such as ocular solar exposure
and colder ambient temperature may be involved in disease pathogenesis.
Prospective studies have also implicated higher coffee consumption and lower
dietary folate intake in association with incident XFS. The discovery of
environmental risk factors for XFS suggests that preventive measures may help to
reduce ocular morbidity from XFS.
PMID- 29965899
TI - Composition of Exfoliation Material.
AB - Exfoliation glaucoma (XFG) is the most common identifiable cause of open-angle
glaucoma worldwide, and results from the accumulation of extracellular fibrillary
material (XFM) within the trabecular meshwork and the Schlemm canal leading to
increased intraocular pressure and potential blindness. Immunohistochemical and
mass spectrometry analyses have revealed that XFM is a highly glycosylated
proteinaceous complex that is extremely resistant to degradation both within the
body and under experimental conditions. The protein core contains a wide variety
of proteins, including basement membrane proteins, elastic fiber proteins, latent
TGFbeta proteins, metalloproteinases, chaperone proteins, complement proteins,
lysyl oxidase-like 1 (LOXL1), and apolipoprotein E (ApoE). This supplemental
section identifies the advances in knowledge and current understanding of the
components within XFM with a specific focus on the most recent work defining
proteins within XFM and to pose several biological questions that remain
unanswered.
PMID- 29965900
TI - A Role for Clusterin in Exfoliation Syndrome and Exfoliation Glaucoma?
AB - The multifunctional protein clusterin (CLU) is a secreted glycoprotein
ubiquitously expressed throughout the body, including in the eye. Its primary
function is to act as an extracellular molecular chaperone, preventing the
precipitation and aggregation of misfolded extracellular proteins. Clusterin is
commonly identified at fluid-tissue interfaces, and has been identified in most
body fluids. It is a component of exfoliation material, and CLU mRNA is reduced
in eyes with exfoliation syndrome compared with controls. SNPs located in the CLU
genomic region have been associated with Alzheimer disease (AD) at the genome
wide level and several CLU SNPs located in an apparent regulatory region have
been nominally associated with XFS/XFG in Caucasians with European ancestry and
in south Indians. Interestingly, clusterin associates with altered elastic fibers
in human photoaged skin and prevents UV-induced elastin aggregation in vitro. In
light of the known geographic risk factors for XFS/XFG, which could include UV
light, investigations of CLU-geographic interactions could be of interest. Future
studies investigating rare CLU variation and other complex interactions including
gene-gene interactions in XFS/XFG cases and controls may also be fruitful.
Although CLU has been considered as a therapeutic target in AD, cancer and dry
eye, a role for clusterin in XFS/XFG needs to be better defined before
therapeutic approaches involving CLU can be entertained.
PMID- 29965901
TI - Utah Project on Exfoliation Syndrome (UPEXS): Insight Into Systemic Diseases
Associated With Exfoliation Syndrome.
AB - The Utah Project on Exfoliation Syndrome (UPEXS) study was created to investigate
the association between exfoliation syndrome (XFS) and systemic disorders or
pathologies. The study utilizes the resources of the Utah Population Database,
which is linked to the Utah genealogy, a compilation of large pedigrees extending
back 3 to >=11 generations, representing most families in the state. These family
members medical and health records are linked to vital records and can be used
effectively to identify familial clustering of disorders, like XFS, with comorbid
diseases or health-related data. There is growing evidence that XFS patients have
an increased risk for systemic disorders that may reflect the systemic tissue
involvement of this disease. Epidemiologic studies of individuals with XFS have
reported an increased risk of various pathologies that have abnormalities in
extracellular matrix metabolism and repair. For this reason, the UPEXS has
focused on disorders that involve the extracellular matrix in general and elastin
specifically, such as pelvic organ prolapse, atrial fibrillation, inguinal
hernias, and chronic obstructive pulmonary disease. In this paper we present our
results from the analysis of pelvic organ prolapse, as well as, preliminary data
for atrial fibrillation.
PMID- 29965902
TI - Medical Management of Glaucoma in Exfoliation Syndrome.
AB - The treatment of glaucoma in exfoliation syndrome is similar to primary open
angle glaucoma. Frequently, exfoliation glaucoma (XFG) patients require early
polytherapy with topical medications. Little emphasis has been placed on
tailoring treatment specifically to XFG. New outflow enhancing agents with novel
mechanisms of action, such as Rho Kinase inhibition, NO signaling (both recently
FDA-approved drugs) and adenosine alpha1-receptor stimulation, act directly on
the trabecular meshwork. These agents may prove to be effective in lowering
intraocular pressure and perhaps altering the pathogenesis of XFG aid in the long
term management of this disease.
PMID- 29965904
TI - Exfoliation Syndrome and Cataract Surgery.
AB - Cataract extraction in exfoliation syndrome requires careful preoperative
assessment and planning. Knowledge of the degree of pupil dilation and zonular
integrity are essential for safely perform cataract surgery in these eyes.
Capsule rhexis should be 5.5 mm and all intraoperative maneuvers should be
designed to minimize zonular stress. The surgeon should be versatile in various
nuclear disassembly techniques and consider use of capsular support devices when
warranted. Cortical cleanup should proceed via a tangential approach and attempts
should be made to removal residual lens epithelial cells so as to minimize
postoperative capsular contraction syndrome.
PMID- 29965905
TI - Clinical and Laboratory Biomarkers for Pseudoexfoliation Syndrome.
AB - In this review, we present an update on biomarkers (both clinical and laboratory)
on the basis of recent peer-reviewed publications relating to pseudoexfoliation
syndrome and pseudoexfoliation glaucoma.
PMID- 29965903
TI - Recent Advances in the Surgical Management of Glaucoma in Exfoliation Syndrome.
AB - Surgical and laser procedures traditionally used in the management of exfoliation
glaucoma (XFG) include laser trabeculoplasty, trabeculectomy, and glaucoma
drainage implant surgery. Having demonstrated similar safety and efficacy in XFG
compared with primary open-angle glaucoma, trabeculectomy remains the most
commonly performed surgery in XFG. Recent trends in practice patterns in
developed nations demonstrate a shift towards glaucoma drainage implant surgery,
which is currently the procedure of choice in XFG for many, particularly in
developed nations. In addition, cataract surgery alone may significantly decrease
intraocular pressure in patients with XFG, may prevent glaucoma development in
patients with exfoliation syndrome, and is recommended to be performed early in
the course of the disease. With the relatively recent introduction of
nonpenetrating glaucoma surgery and the ongoing evolution of minimally invasive
glaucoma surgery, several other surgical procedures have now become part of the
glaucoma surgeon's armamentarium when treating XFG, including the Ex-PRESS shunt,
deep sclerectomy, viscocanalostomy, Trabectome, as well as angle procedures.
These techniques have demonstrated promising results in various types of
glaucoma. More research is, however, needed to establish the safety and efficacy
of these procedures in XFG.
PMID- 29965906
TI - Bridging the Gap: A 20-Year Experience with Vein Grafts for Free Flap
Reconstruction. The Odds for Success.
AB - BACKGROUND: Successful free tissue transfer requires tension-free microvascular
anastomosis. Vein grafts are used when this cannot be obtained, which increases
microsurgical complexity and the chance of vessel thrombosis. Previous studies on
vein grafts are limited to low numbers and selected techniques, making it
difficult to draw conclusions. METHODS: A retrospective chart review was
performed for all patients who underwent vein grafts in free flap reconstruction
from 1995 to 2015. Information on patient and flap characteristics, returns to
the operating room, and flap loss was analyzed. RESULTS: Seventy-two free flap
reconstructions requiring 122 vein grafts were performed in the
genitourinary/perineal (49 percent) and head and neck (38 percent) regions. The
majority were performed in the initial operation (82 percent) and, of those, the
majority were planned (71 percent). The most common vein graft types used were
transposition arteriovenous loops (57 percent) and interpositions (26 percent).
Of the initial cases, 22 percent returned to the operating room, resulting in a 7
percent total flap loss rate and a 7 percent partial flap loss rate. On
univariate analysis, graft timing/planning, gap type, vein graft type, and
reconstruction location were significantly associated with take-backs and flap
loss. However, gap type and location seem to be strongly associated with graft
timing/planning and vein graft type. Graft type and planning/timing do not have
as strong a relationship and seem to independently relate to flap loss.
CONCLUSIONS: Vein grafts are more successful when planned and when performing
transpositions and arteriovenous loops over interpositions. These graft types
should be considered over interpositions when possible. CLINICAL QUESTION/LEVEL
OF EVIDENCE: Therapeutic, IV.
PMID- 29965907
TI - Reply: Antithrombotic Therapies in Digit Replantation with Papaverine
Administration: A Prospective, Observational Study.
PMID- 29965908
TI - Reply: Macrotextured Breast Implants with Defined Steps to Minimize Bacterial
Contamination around the Device: Experience in 42,000 Implants.
PMID- 29965909
TI - The Economics of Prepectoral Breast Reconstruction.
PMID- 29965910
TI - Objective Assessment of the Unilateral Cleft Lip Nasal Deformity Using Three
Dimensional Stereophotogrammetry: Severity and Outcome.
PMID- 29965911
TI - Letter to the Editor: A matter of eponyms.
PMID- 29965912
TI - Macrotextured Breast Implants with Defined Steps to Minimize Bacterial
Contamination around the Device: Experience in 42,000 Implants.
PMID- 29965913
TI - Reply: Smaller Diameter Anastomotic Coupling Devices Have Higher Rates of Venous
Thrombosis in Microvascular Free Tissue Transfer.
PMID- 29965915
TI - Reply: Objective Assessment of the Unilateral Cleft Lip Nasal Deformity Using
Three-Dimensional Stereophotogrammetry: Severity and Outcome.
PMID- 29965914
TI - A Novel Innovation for Surgical Flap Markings Using Projected Stencils.
AB - : Despite the vast amount of technological advancement seen in the operating
room, surgical markings are still drawn as "best estimates" the same way Susruta
drew them in the sixth century BC. Many of the flaps used in plastic surgery have
precise geometries that are hard to replicate by hand. In this article, the
authors describe a novel approach in making surgical markings more accurate by
using a pico-projector to project a prefabricated flap, designed on Google
Sketchup, as a stencil. Projected and hand-drawn rhomboid and bilobed flaps were
tested on cadavers, with both quantitative and qualitative outcomes favoring the
projected flaps. This unique concept can not only be used in the operating room
but also serve as an educational tool for training plastic and reconstructive
surgeons. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.
PMID- 29965916
TI - Smaller Diameter Anastomotic Coupling Devices Have Higher Rates of Venous
Thrombosis in Microvascular Free Tissue Transfer.
PMID- 29965917
TI - Acellular Dermal Matrix in Immediate Expander/Implant Breast Reconstruction: A
Multicenter Assessment of Risks and Benefits.
PMID- 29965918
TI - Ethics in Plastic Surgery: Applying the Four Common Principles to Practice.
AB - The topic of ethics in plastic surgery remains underrepresented in the
literature. By applying the four principles of biomedical ethics-respect for
autonomy, beneficence, nonmaleficence, and justice-as described by Beauchamp and
Childress to proposed ethical scenarios, this article attempts to provide plastic
surgeons with a systematic approach to recognize and address ethical dilemmas as
they present in day-to-day practice. Through the perspective of an experienced
plastic surgeon and medical ethicist, this article is intended to spark
discussion, reflection, and debate on ethical challenges in plastic surgery.
PMID- 29965919
TI - Antithrombotic Therapies in Digit Replantation with Papaverine Administration: A
Prospective, Observational Study.
PMID- 29965920
TI - Lymph Flow Restoration after Tissue Replantation and Transfer: Importance of
Lymph Axiality and Possibility of Lymph Flow Reconstruction without Lymph Node
Transfer or Lymphatic Anastomosis.
AB - BACKGROUND: The lymph system plays important roles in maintaining fluid balances,
the immune system, and lipid metabolism. After tissue replantation or transfer,
some cases suffer long-lasting edema or lymphedema caused by interruption of main
lymph flows; however, this mechanism has yet to be clarified. METHODS: The
medical charts of 38 patients who underwent indocyanine green lymphography after
tissue replantation or free flap transfer were reviewed to obtain data regarding
clinical demographics, intraoperative findings, and postoperative indocyanine
green lymphographic findings. Postoperative lymph flow restoration based on
indocyanine green lymphographic findings was evaluated according to
intraoperative findings, including raw surface in lymph axiality and compatible
lymph axiality. RESULTS: Lymph flow restoration was observed in 24 cases (63
percent). There were significant differences in positive lymph flow restoration
with regard to sex (male, 78 percent; female, 40 percent; p = 0.017), cause of
defect (trauma, 83 percent; others, 33 percent; p = 0.002), type of operation
(replantation, 94 percent; free flap, 41 percent; p = 0.001), and compatible
lymph axiality (positive, 96 percent; negative, 0 percent; p < 0.001). Based on
lymph axiality, the raw surface in lymph axiality-negative and compatible lymph
axiality-positive condition was completely matched with lymph flow restoration
positivity; 100 percent accuracy to predict postoperative lymph flow restoration
was observed. CONCLUSIONS: Lymph flow can be restored after tissue replantation
or free flap transfer without lymph node or supermicrosurgical lymphatic
anastomosis. The raw surface in lymph axiality-negative and compatible lymph
axiality-positive condition is considered a key for restoring lymph flows after
surgery affecting the main lymph pathway. CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
PMID- 29965921
TI - Cultural Considerations Regarding Glansplasty.
PMID- 29965922
TI - Reply: The Role of Tranexamic Acid in Plastic Surgery: Review and Technical
Considerations.
PMID- 29965923
TI - The Role of Tranexamic Acid in Plastic Surgery: Review and Technical
Considerations.
PMID- 29965924
TI - Reconstruction of the Heel, Middle Foot Sole, and Plantar Forefoot with the
Medial Plantar Artery Perforator Flap: Clinical Experience with 28 Cases.
PMID- 29965925
TI - Longitudinal Data Highlighting the Inability to Maintain Medical Student Interest
in Plastic Surgery.
PMID- 29965926
TI - Caution with Use: Smartphone-Related Distracted Behaviors and Implications for
Pedestrian Trauma.
PMID- 29965927
TI - Rethinking Evidence-Based Medicine in Plastic and Reconstructive Surgery.
PMID- 29965929
TI - Reply: Reconstruction of the Heel, Middle Foot Sole, and Plantar Forefoot with
the Medial Plantar Artery Perforator Flap: Clinical Experience with 28 Cases.
PMID- 29965928
TI - Treatment of cervicofacial lymphatico-venous malformation with vascularized lymph
node transfer (VLNT).
PMID- 29965930
TI - Reply to Letter: Patient-reported outcome measures following rhinoplasty.
PMID- 29965931
TI - Is the "Appropriate Use Criteria" for Type II Supracondylar Humerus Fractures
Really Appropriate?
PMID- 29965932
TI - Arthroscopic Capsulolabral Reconstruction for Posterior Shoulder Instability is
Successful in Adolescent Athletes.
AB - BACKGROUND: Posterior shoulder instability is an increasingly common pathology
recognized in athletes. Adolescent athletes are especially at risk for this
condition due to the widespread participation in numerous sports, including both
overhead throwing and collision activities. Little data are available regarding
surgical outcomes in these athletes with only a single small case series (N=25)
currently published. METHODS: In total, 68 athletes (82 shoulders) with
unidirectional posterior shoulder instability were treated with arthroscopic
posterior capsulolabral reconstruction and underwent an evaluation at a mean of
36 months postoperatively. The average age for our cohort was 17.2 years (range,
14 to 19 y), with 66 males (80%) and 16 females (20%). A total of 55 athletes
(67%) participated in contact sports and 32 athletes (39%) participated in
overhead throwing. Thirty athletes (37%) participated in multiple sports.
Preoperative and postoperative outcomes data were retrospectively reviewed, and
included the American Shoulder and Elbow Surgeons (ASES) shoulder score,
subjective stability score, strength, range of motion, and return-to-play status.
Intraoperative findings and methods of fixation were also recorded. RESULTS: Mean
ASES score improved from 48.6 to 85.7 (P<0.001) after surgery. There were also
significant improvements in stability, pain, and functional scores after surgery.
Contact, throwing, and multisport athletes all showed similar scores at
preoperative and follow-up timepoints, and no differences were noted between
these athlete groups for any patient-reported outcome measure. Female athletes
tended to have significantly lower preoperative and postoperative ASES scores,
specifically within the pain domain when compared with males. With regard to the
method of internal fixation, patients who underwent capsulolabral plications with
suture anchors showed a trend toward greater improvement in ASES scores which did
not reach statistical significance. Overall, 89% of athletes were able to return
to competition, with 71% returning to their preinjury level of play. In total,
8.5% of athletes failed their initial surgical procedure with continued pain or
instability that required revision surgery. CONCLUSIONS: Arthroscopic
capsulolabral reconstruction is a reliable treatment for unidirectional posterior
shoulder instability in an adolescent population, and does well for athletes
involved in a variety of sporting activities. LEVEL OF EVIDENCE: Level IV-case
series.
PMID- 29965933
TI - Gross Motor Function at 10 Years of Age in Children With Clubfoot Following the
French Physical Therapy Method and the Ponseti Technique.
AB - PURPOSE: To evaluate gross motor skills [Bruininks-Oseretsky Test of Motor
Proficiency, 2nd ed (BOT-2)] of patients with idiopathic clubfoot initially
treated nonoperatively with either the French functional physical therapy (PT)
method or the Ponseti technique, at age 10 years. METHODS: The BOT-2 was
administered by trained physical therapists on patients with idiopathic clubfoot
at age 10 years. The cohort was divided by initial treatment method (PT or
Ponseti), and compared. Subsequent analyses included comparisons of: initial
clubfoot severity (Dimeglio scores: <=13 vs. >13), laterality (unilateral vs.
bilateral), and surgical versus nonoperative outcome. RESULTS: Of the 183
patients tested, 172 were included. The Ponseti and PT groups did not
significantly differ according to age, height, weight, body mass index, ankle
dorsiflexion, sex, average initial Dimeglio score, laterality, or surgical versus
nonsurgical outcome. Overall, patients with treated clubfoot had average gross
motor BOT-2 scores compared with age-matched peers. Patients in the PT group
scored higher on Running Speed/Agility (P=0.019), Body Coordination percentile
rank (P=0.038), and Strength and Agility percentile rank (P=0.007) than patients
treated by the Ponseti technique. Patients with bilateral clubfoot scored
significantly lower on the Balance subtest (P<0.01), and Body Coordination
percentile rank (P<0.01), than those with unilateral clubfoot. Patients who
required surgery scored significantly lower on the Balance subtest (P=0.04) than
those who did not require surgery. CONCLUSIONS: Clubfoot may impair balance in 10
year olds with bilateral involvement and those requiring surgery. Future research
should evaluate whether components of the PT method may improve gross motor
outcomes as a supplement to the Ponseti technique. LEVELS OF EVIDENCE: Level II.
PMID- 29965934
TI - Arthroscopic Elbow Contracture Release in the Pediatric Patient.
AB - BACKGROUND: Elbow contracture is a sequelae of elbow trauma in pediatric
patients. Arthroscopic contracture release has been shown to provide equivalent
results to open contracture release with less associated morbidity and
complications in the adult population. However, open contracture release is still
commonly utilized in pediatric patients. The goal of this study is to determine
the clinical results and safety profile of arthroscopic elbow contracture release
in the pediatric population. METHODS: A retrospective review of all patients 18
years of age and younger who underwent arthroscopic elbow contracture release was
performed. Demographic statistics, indication for surgery, preoperative and
postoperative flexion-extension and pronation-supination range of motion, and all
complications were recorded and analyzed. RESULTS: Twenty-five patients were
identified as having undergone 29 arthroscopic elbow contracture releases. The
most common index injury was elbow contracture after radial head fracture. The
flexion-extension arc of motion improved from 93.0+/-39.9 degrees to 128.0+/-19.2
degrees for a total improvement of 35.2 degrees (P=0.0002), whereas the pronation
supination arc of motion improved from 141.0+/-58.6 degrees to 153+/-49.3 degrees
for a total improvement of 12.2 degrees (P=0.097). There were 7 total
complications. CONCLUSIONS: Arthroscopic elbow contracture release allows for
restoration of range of motion with an acceptable safety profile and can be
considered as a less invasive alternative to open contracture release in the
pediatric population. LEVEL OF EVIDENCE: Level IV.
PMID- 29965935
TI - Azithromycin and Sensorineural Hearing Loss in Adults: A Retrospective Cohort
Study.
AB - OBJECTIVE: To examine whether short-term use of azithromycin increases the risk
of sensorineural hearing loss (SNHL) in adults with uncomplicated infections.
STUDY DESIGN: A retrospective cohort study using Medicaid claims data, 1999 to
2010. PATIENTS: Adults (18-64 years old) who had continuous enrollment in
Medicaid for the 12 months (baseline) before the date of first dispensation
(index date) of oral azithromycin or amoxicillin +/- clavulanate for
uncomplicated infections. MAIN OUTCOME DEFINITION: We operationalized
sensorineural hearing loss (SNHL) by a charge for audiometry and followed by a
diagnosis of SNHL within 30 days. ANALYSIS: We adjusted for the baseline
covariates through propensity score matching. Adults were followed for up to 120
days after the index date. The hazard of SNHL in azithromycin-exposed adults was
compared with those who had amoxicillin +/- clavulanate using a Cox proportional
hazard model. We performed several sensitivity analyses by varying the follow-up
time, SNHL definition, adjusting for cumulative antibiotic use, and switching
exposure status during the follow-up period. RESULTS: A total of 493,774 patients
entered the study cohort. The unadjusted incidence rates of SNHL were 38 and 41
cases per 10,000 patient-years following exposure to azithromycin and amoxicillin
+/- clavulanate, respectively. The adjusted (matched) hazard ratio (HR) of SNHL
for azithromycin versus amoxicillin +/- clavulanate was 0.91 (95% confidence
interval [CI], 0.77-1.07). The sensitivity analyses findings were consistent with
the primary analysis. CONCLUSION: Azithromycin short-term use was not associated
with an increased risk of SNHL in comparison to amoxicillin +/- clavulanate.
PMID- 29965936
TI - NEGATIVE EFFECTS OF VITAL DYES AFTER UNEVENTFUL VITREOMACULAR SURGERY.
AB - PURPOSE: Vital dyes have become a clinical standard during chromovitrectomy but
toxicity remains an issue. We compared the clinical outcome of one supposedly
toxic vital dye (AV 17 with 5% mannitol) with a standard vital dye (MBB Dual) and
performed a power analysis for future comparative studies. METHODS: Retrospective
analysis of 270 eyes after chromovitrectomy with internal limiting membrane
peeling because of macular holes. Primary endpoint was loss in BCVA >2 lines and
photoreceptor atrophy as seen on optical coherence tomography examination.
RESULTS: In 173 eyes, staining of the epiretinal membrane and extracellular
matrix was performed using MBB (Group A), and in 97 using AV 17-M (Group B). The
mean BCVA was not significantly different after more than 3 months and also not
in the early postoperative period after surgery between Group A and Group B. The
number of patients suffering from a decline in BCVA of two lines and more was not
significantly higher in patients of Group B. There was not a significantly higher
percentage of patients with an inner segment/outer segment defect. CONCLUSION:
Our rather homogeneous study showed no significant difference between both dyes.
Thousand five hundred patients would need to be examined to find a significant
difference in future studies.
PMID- 29965937
TI - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHARACTERISTICS OF POLYPOIDAL CHOROIDAL
VASCULOPATHY SECONDARY TO CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.
AB - PURPOSE: To report diagnostic capability of optical coherence tomography
angiography (OCTA) in detecting polypoidal choroidal vasculopathy and its
morphologic characteristics in white patients with chronic central serous
chorioretinopathy. METHODS: Retrospective consecutive series of 20 eyes (17
consecutive patients) with a diagnosis of polypoidal choroidal vasculopathy
secondary to chronic central serous chorioretinopathy based on clinical and
multimodal imaging were included. All patients underwent a complete
ophthalmologic examination, including best-correct visual acuity, fundus
autofluorescence, fluorescein and indocyanine green angiography, spectral-domain
optical coherence tomography, and OCTA. RESULTS: In all eyes (100%), OCTA
revealed the branching vascular network as a hyperflow lesion in both
choriocapillaris and outer retina layers. Segmentation of the choriocapillaris in
OCTA, in correspondence of the polypoidal dilation detected at indocyanine green
angiography, showed a hyperflow round structure in 75% of cases and hypoflow
round structure in 15%. Two of 20 eyes (10%) had no detectable polyps on OCTA.
CONCLUSION: Optical coherence tomography angiography is a noninvasive imaging
modality allowing a good visualization of both branching vascular network and
polyp dilations. Our findings suggest that OCTA is a useful tool in the
investigation of chronic central serous chorioretinopathy complicated by
polypoidal choroidal vasculopathy.
PMID- 29965938
TI - RESOLUTION, DEPTH OF FIELD, AND PHYSICIAN SATISFACTION DURING DIGITALLY ASSISTED
VITREORETINAL SURGERY.
AB - PURPOSE: To evaluate depth of field, lateral resolution, and image quality of a
heads-up 3D visualization system for vitreoretinal surgery using physician survey
and optical measurement outcomes. METHODS: Depth of field and lateral resolution
were compared between the standard ocular viewing system and the digital 3D
system at *5, *13, and *18 magnification by 6 retinal surgeons. Optical
techniques were used as well as a survey of surgeon impression. Surgeon
impression surveys were performed after 6 weeks of surgical use of the device.
RESULTS: Physician questionnaire survey scores for depth of field at high
magnification were better for the digital 3D system and equivalent for all other
categories. Measured lateral resolution was 36.7 mm and 16.6 mm at *5
magnification (P < 0.001), 14.3 mm and 6.4 mm at *13 magnification (P < 0.001),
and 9.8 mm and 4.2 mm (P < 0.001) at *18 magnification for the digital 3D and
oculars, respectively. Measured depth of field was 4.00 mm and 6.78 mm at *5
magnification (P = 0.027), 0.72 mm and 0.86 mm at *13 (P = 0.311), and 0.28 mm
and 0.40 mm at *18 magnification (P = 0.235) for the oculars and digital 3D,
respectively. CONCLUSION: Lateral resolution of the digital 3D system was half
that of the ocular viewing system and there was some improvement in depth of
field with the digital system. Surgeon impression suggested that the digital
system was superior when evaluating depth of field at high magnification.
PMID- 29965939
TI - Mobile forward-looking infrared technology allows rapid assessment of
resuscitative endovascular balloon occlusion of the aorta in hemorrhage and
blackout conditions.
AB - INTRODUCTION: Objective assessment of final resuscitative endovascular balloon
occlusion of the aorta (REBOA) position and adequate distal aortic occlusion is
critical in patients with hemorrhagic shock, especially as feasibility is being
increasingly investigated in the prehospital setting. We propose that mobile
forward-looking infrared (FLIR) thermal imaging is a fast, reliable, and
noninvasive method to assess REBOA position and efficacy in scenarios applicable
to battlefield and prehospital care. METHODS: Ten swine were randomized to a 40%
hemorrhage group (H, n = 5) or nonhemorrhage group (NH, n = 5). Three experiments
were completed after Zone I placement of a REBOA catheter. Resuscitative
endovascular balloon occlusion of the aorta was deployed for 30 minutes in all
animals followed by randomized continued deployment versus sham in both light and
blackout conditions. Forward-looking infrared images and hemodynamic data were
obtained. Images were presented to 62 blinded observers for assessment of REBOA
inflation status. RESULTS: There was no difference in hemodynamic or laboratory
values at baseline. The H group was significantly more hypotensive (mean arterial
pressure 44 vs. 60 mm Hg, p < 0.01), vasodilated (systemic vascular resistance
634 vs. 938dyn.s/cm, p = 0.02), and anemic (hematocrit 12 vs. 23.2%, p < 0.01).
Hemorrhage group animals remained more hypotensive, anemic, and acidotic
throughout all three experiments. There was a significant difference in the
temperature change (DeltaTemp) measured by FLIR between animals with REBOA
inflated versus not inflated (5.7 degrees C vs. 0.7 degrees C, p < 0.01). The H
and NH animals exhibited equal magnitudes of DeltaTemp in both inflated and
deflated states. Blinded observer analysis of FLIR images correctly identified
adequate REBOA inflation and aortic occlusion 95.4% at 5 minutes and 98.8% at 10
minutes (positive predictive value at 5 minutes = 99% and positive predictive
value at 10 minutes = 100%). CONCLUSIONS: Mobile thermal imaging is an easy,
rapid, and reliable method for assessing distal perfusion after occlusion by
REBOA. Smartphone-based FLIR technology allows for confirmation of adequate REBOA
placement at the point of care, and performance was not degraded in the setting
of major hemorrhage or blackout conditions.
PMID- 29965940
TI - Deconstructing dogma: Nonoperative management of small bowel obstruction in the
virgin abdomen.
AB - BACKGROUND: Management of small bowel obstruction (SBO) has become more
conservative, especially in those patients with previous abdominal surgery (PAS).
However, surgical dogma continues to recommend operative exploration for SBO with
no PAS. With the increased use of computed tomography imaging resulting in more
SBO diagnoses, it is important to reevaluate the role of mandatory operative
exploration. Gastrografin (GG) administration decreases the need for operative
exploration and may be an option for SBO without PAS. We hypothesized that the
use of GG for SBO without PAS will be equally effective in reducing the operative
exploration rate compared with that for SBO with PAS. METHODS: A post hoc
analysis of prospectively collected data was conducted for patients with SBO from
February 2015 through December 2016. Patients younger than 18 years, pregnant
patients, and patients with evidence of hypotension, bowel strangulation,
peritonitis, closed loop obstruction or pneumatosis intestinalis were excluded.
The primary outcome was operative exploration rate for SBO with or without PAS.
Rate adjustment was accomplished through multivariate logistic regression.
RESULTS: Overall, 601 patients with SBO were included in the study, 500 with PAS
and 101 patients without PAS. The two groups were similar except for age, sex,
prior abdominal surgery including colon surgery, prior SBO admission, and history
of cancer. Multivariate analysis showed that PAS (odds ratio [OR], 0.47; p =
0.03) and the use of GG (OR, 0.11; p < 0.01) were independent predictors of
successful nonoperative management, whereas intensive care unit admission (OR,
16.0; p < 0.01) was associated with a higher likelihood of need for operation.
The use of GG significantly decreased the need for operation in patients with and
without PAS. CONCLUSIONS: Patients with and without PAS who received GG had lower
rates of operative exploration for SBO compared with those who did not receive
GG. Patients with a diagnosis of SBO without PAS should be considered for the
nonoperative management approach using GG. LEVEL OF EVIDENCE: Therapeutic, level
IV.
PMID- 29965941
TI - Location is everything: The hemodynamic effects of REBOA in Zone 1 versus Zone 3
of the aorta.
AB - OBJECTIVES: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is
an emerging technology to augment proximal blood pressure during the
resuscitation of patients with noncompressible torso hemorrhage. Currently,
placement choice, supraceliac (Zone 1) versus infrarenal (Zone 3) aorta, depends
on injury patterns, but remains a highly debated topic. We sought to compare the
proximal hemodynamic support provided by Zone 1 versus Zone 3 REBOA placement and
the degree of hemodynamic instability upon reperfusion following intervention.
METHODS: Eighteen anesthetized swine underwent controlled hemorrhage of 25% total
blood volume, followed by 45 minutes of Zone 1 REBOA, Zone 3 REBOA, or no
intervention (control). They were then resuscitated with shed blood, aortic
balloons were deflated, and 5 hours of critical care ensued prior to euthanasia.
Physiologic parameters were recorded continuously, and blood was drawn for
analysis at specified intervals. Significance was defined as p < 0.05. RESULTS:
There were no significant differences between groups at baseline or during the
initial 30 minutes of hemorrhage. During the intervention period, average
proximal MAP was significantly greater in Zone 1 animals when compared with Zone
3 animals (127.9 +/- 1.3 vs. 53.4 +/- 1.1 mm Hg) and greater in Zone 3 animals
when compared with control animals (42.9 +/- 0.9 mm Hg). Lactate concentrations
were significantly higher in Zone 1 animals (9.6 +/- 0.4 mmol/L) when compared
with Zone 3 animals (5.1 +/- 0.3 mmol/L) and control animals (4.2 +/- 0.8
mmol/L). CONCLUSIONS: In our swine model of hemorrhagic shock, Zone 3 REBOA
provided minimal proximal hemodynamic support when compared with Zone 1 REBOA,
albeit with less ischemic burden and instability upon reperfusion. In cases of
impending hemodynamic collapse, Zone 1 REBOA placement may be more efficacious
regardless of injury pattern, whereas Zone 3 should be reserved only for
relatively stable patients with ongoing distal hemorrhage.
PMID- 29965942
TI - Neurosurgical workload during US combat operations: 2002 to 2016.
AB - BACKGROUND: Approximately 4.5% of surgical procedures performed at Role 2 (R2)
(forward surgical) and Role 3 (R3) (theater) medical treatment facilities can be
classified as neurosurgical. These procedures are foreign to the routine daily
practice of the military general surgeon. The purpose of this study was to
examine the neurosurgical workload in Iraq and Afghanistan in order to inform the
future predeployment neurosurgical training needs of nonneurosurgical providers.
METHODS: Retrospective analysis of the Department of Defense Trauma Registry for
all R2 and R3 medical facilities, from January 2002 to May 2016. The 103
neurosurgical International Classification of Diseases, Ninth Revision, Clinical
Modification procedure codes identified were grouped by anatomic location. Select
groups were further subdivided. Data analysis used Stata version 14 (College
Station, TX). RESULTS: A total of 7,509 neurosurgical procedures were identified.
The majority (7,244 [96.5%]) occurred at R3 theater hospitals. Cranial procedures
were the most common at both R2 (120, 45.3%) and R3 (4,483 [61.9%]), with
craniotomy/craniectomy the most frequent procedure. Spine procedures were
performed almost exclusively at R3, with 61.1% being fusions/stabilizations and
26.9% being spinal decompression alone. Neurosurgical caseload was variable over
the 15-year study period, dropping to almost zero in 2016. CONCLUSIONS:
Neurosurgical procedures were performed primarily at larger R3 theater hospitals
where neurosurgeons were assigned if present in theater; however, more than 100
cranial procedures were performed at forward R2 where neurosurgeons were not
deployed. Considering that neurosurgeons are not everywhere available within the
war zone, deploying general surgeons should have familiarity with trauma
neurosurgery. LEVEL OF EVIDENCE: Epidemiologic study, level III; Care Management,
level IV.
PMID- 29965943
TI - Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic
Risk in the Community.
AB - OBJECTIVE: The complex relationship between psychosocial stress over the
lifetime, psychological factors, and cardiometabolic risk is still poorly
understood. Accordingly, our aims were (1) to independently assess the
associations between childhood adversity, life-event stress in remote (earlier
than the last 5 years), and recent adulthood and cardiometabolic risk, and (2) to
determine the role of psychological factors including personality, coping, and
depression in these associations. METHODS: The sample included 2674 adults, aged
35 to 66 years, randomly selected from urban area. Participants underwent a
physical examination including the assessment of obesity markers, blood pressure,
and blood lipid and glucose levels. Stress during adulthood was determined using
the severity scores of 52 stressful life events. Information on adverse childhood
experiences and major depressive disorders was collected using semistructured
interviews, whereas personality traits and coping mechanisms were evaluated
through questionnaires. RESULTS: Both childhood adversity and stress in remote
adulthood were associated with elevated body mass index (beta [95% confidence
interval {CI}] = 0.249 [0.029 to 0.468]; 0.020 [0.006 to 0.034]), waist
circumference (beta [95% CI] = 0.061 [0.024 to 0.099]; 0.08 [0.04 to 0.11]), and
the global cardiometabolic risk score (beta [95% CI] = 0.278 [0.017 to 0.540];
0.017 [0.001 to 0.033]) after adjustment for sociodemographic, lifestyle, and
psychological factors. In addition, childhood adversity was associated with low
high density lipoprotein levels (beta [95% CI] = -0.021 [-0.042 to 0.000]), as
well as increased fat mass and systolic blood pressure levels (beta [95% CI] =
0.506 [0.165 to 0.846]; 0.952 [0.165 to 1.740]) and stress in remote adulthood
with apolipoprotein B levels (beta [95% CI] = 0.607 [0.312 to 0.901]).
Psychological factors did not account for these associations and were not effect
modifiers. CONCLUSIONS: Our data demonstrate that psychosocial stress during
childhood and remote adulthood favor adiposity and abnormal lipid metabolism.
PMID- 29965944
TI - The Role of Norepinephrine and alpha-Adrenergic Receptors in Acute Stress-Induced
Changes in Granulocytes and Monocytes.
AB - OBJECTIVE: Acute stress induces redistribution of circulating leucocytes in
humans. Although effects on lymphocytes as adaptive immune cells are well
understood, the mechanisms underlying stress effects on granulocytes and
monocytes as innate immune blood cells are still elusive. We investigated whether
the stress hormone norepinephrine (NE) and alpha-adrenergic receptors (alpha
ADRs) may play a mediating role. METHODS: In a stress study, we cross-sectionally
tested 44 healthy men for associations between stress-induced NE increases and
simultaneous granulocyte and monocyte cell count increases, as measured
immediately before and several times after the Trier Social Stress Test. In a
subsequent infusion study, 21 healthy men participated in three different
experimental trials with sequential infusions of 1- and 15-minute duration with
varying substances (saline as placebo, the nonspecific alpha-ADR blocker
phentolamine [2.5 mg/min], and NE [5 MUg/min]): trial 1 = saline+saline, trial 2
= saline+NE, trial 3 = phentolamine+NE. Granulocyte and monocyte cell numbers
were assessed before, immediately after, 10 minutes, and 30 minutes after
infusion procedures. RESULTS: In the stress study, higher NE related to higher
neutrophil stress changes (beta = .31, p = .045, R change = .09), but not
epinephrine stress changes. In the infusion study, saline+NE induced significant
increases in neutrophil (F(3/60) = 43.50, p < .001, eta = .69) and monocyte
(F(3/60) = 18.56, p < .001, eta = .48) numbers compared with saline+saline. With
phentolamine+NE, neutrophil (F(3/60) = 14.41, p < .001, eta = .42) and monocyte
counts (F(2.23/44.6) = 4.32, p = .016, eta = .18) remained increased compared
with saline+saline but were lower compared with saline+NE (neutrophils: F(3/60) =
19.55, p < .001, eta = .494, monocytes: F(3/60) = 2.54, p = .065, eta = .11)
indicating partial mediation by alpha-ADRs. Trials did not differ in eosinophil
and basophil count reactivity. CONCLUSIONS: Our findings suggest that NE-induced
immediate increases in neutrophil and monocyte numbers resemble psychosocial
stress effects and can be reduced by blockade of alpha-ADRs.
PMID- 29965945
TI - Fight Fire With Fire: Innovations to Address Syphilis Among Men Who Have Sex With
Men.
PMID- 29965946
TI - Rural-Urban Differences in Human Immunodeficiency Virus Testing Among US Adults:
Findings From the Behavioral Risk Factor Surveillance System.
AB - : Individuals in rural areas of the United States face barriers to human
immunodeficiency virus (HIV)-related health care. We aim to assess differences in
frequency of lifetime and past-year HIV testing, and differences in testing site
location between rural and urban residents of the United States. METHODS: Data
from the Behavioral Risk Factor Surveillance System 2015 were analyzed on 250,579
respondents 18 years or older. Weighted multinomial logistic regression analyses
compared urban/rural differences in lifetime and past-year HIV testing. Weighted
multinomial logistic regression compared urban/rural differences in HIV testing
site. RESULTS: Overall, 26.9% of urban residents and 21.5% of rural residents
reported testing for HIV in their lifetime. Of urban residents, 24.5% reported
receiving an HIV test in the past year compared with 20.2% of rural residents.
Living in a rural area was associated with lower odds of lifetime (odds ratio
[OR], 0.85; 95% confidence interval [CI], 0.81-0.90) and past-year HIV testing
(OR, 0.84; 95% CI, 0.74-0.95) compared with not testing. Rural residents had
higher odds of receiving an HIV test at the hospital or emergency room (adjusted
OR, 1.41; 95% CI, 1.23-1.62) or clinic (adjusted OR, 1.21; 95% CI, 1.02-1.24)
than a doctor's office. CONCLUSIONS: This study highlights significant rural
health disparities in rates of lifetime and past-year HIV testing. Targeted
interventions are needed to remove structural barriers in rural communities, such
as long distances to clinics and low availability of free HIV testing at clinics
serving the uninsured or underinsured. Furthermore, rural providers should be
encouraged to routinely offer HIV screening to their patients.
PMID- 29965947
TI - Heterosexual Anal and Oral Sex in Adolescents and Adults in the United States,
2011-2015.
AB - BACKGROUND: Heterosexual anal and oral sex are related to the acquisition and
transmission of sexually transmitted diseases (STDs). As common reportable STDs
(chlamydia, gonorrhea, and syphilis) in the United States are increasing, it is
important to understand recent oral and anal sexual behaviors. METHODS: We
examined the prevalence and correlates of heterosexual anal and oral sex,
associated condom use, and having multiple partners among men and women aged 15
to 44 years. RESULTS: Approximately one third of women and men had ever engaged
in anal sex, including 11% of adolescents (15-19 years). Most women and men had
ever received or given oral sex (at >75%). Six percent and 7% of women and men,
respectively, used a condom at last oral sex compared with 20% and 30% who used a
condom at last anal sex. Having multiple sex partners in the past year was most
common among adolescents, never or formerly married persons, and those who had a
nonmonogamous partner. Less than 10% reported multiple anal sex partners in the
past year. A substantial minority had multiple oral or anal sex partners; black
women and men had the highest reports of oral sex partners by race/ethnicity.
CONCLUSIONS: Anal and oral sex are common sexual practices. Given the low rates
of condom use during these behaviors, it is important that recommendations for
sexual risk assessments are followed. Tailored messaging regarding risk for STD
and human immunodeficiency virus acquisition during oral and anal sex may benefit
adolescents, singles, and divorced individuals. Future discussions regarding the
benefits of extragenital STD testing for heterosexuals may be useful.
PMID- 29965948
TI - Correlates of Rectal Douching Practices Among Men Who Have Sex With Men in Kenya.
AB - BACKGROUND: Among men who have sex with men (MSM), rectal douching (RD) has been
associated with increased prevalence of human immunodeficiency virus and other
sexually transmitted infections. Substances commonly used for RD, especially
water-based solutions, could disrupt the rectal epithelium and increase
susceptibility to infection. The few existing reports on RD among MSM are
primarily in middle- and high-income settings, and to date, no study has focused
on RD among MSM in Africa. METHODS: We conducted a secondary data analysis of
programmatic data from key population service centers in western Kenya. Data were
extracted from records of clients who identified as MSM and accessed services
between January 1, 2014, and September 1, 2016. We compared demographic and
behavioral characteristics of men who did and did not practice RD. Logistic
regression assessed associations with RD. RESULTS: Of the 202 MSM in this
analysis, 63% engaged in RD. All who engaged in RD used water-based substances.
Those who engaged in receptive anal intercourse in the last 3 months were more
likely to report RD (odds ratio, 3.19; 95% confidence interval, 1.67-6.07). Among
MSM who engaged in sex work, those who practiced RD reported more regular clients
per week (2.8 clients vs. 1.3 clients, P = 0.01). Rectal douching practices did
not vary by other sexual risk practices. CONCLUSIONS: Rectal douching is common
in this population of Kenyan MSM, especially among those who have recently
engaged in receptive anal intercourse, suggesting that a rectal douche that
delivers microbicides could be a potential intervention to reduce human
immunodeficiency virus/sexually transmitted infection within this population.
PMID- 29965949
TI - Triceps Repair and Restoration of Triceps Footprint With Anchorless Suture
Fixation.
AB - Triceps tendon rupture is an uncommon yet potentially devastating injury
affecting patients over a broad demographic. Surgical treatment is essential to
restore upper extremity functional status, and a vast array of techniques has
been implemented with different fixation devices including suture buttons,
intraosseous anchors, and suture repairs. Outcomes of distal triceps tendon
repair have demonstrated nearly full return of functional capacity. Complications
include infection, ulnar nerve neuropathy, arthrofibrosis, flexion contracture,
hardware irritation, and most commonly, repair failure. We illustrate a triceps
repair technique with suture fixation that restores the tendinous footprint
without need of an adjunctive device.
PMID- 29965950
TI - Pharmacokinetic Study of Conversion Between 2 Formulations of Once-daily Extended
release Tacrolimus in Stable Lung Transplant Patients.
AB - BACKGROUND: The aim of this study was to compare the pharmacokinetic profile,
tolerability, and safety of a novel once-daily extended-release formulation of
tacrolimus (LCPT) with that of once-daily prolonged-release tacrolimus (ODT) in
stable adult lung transplant (LT) recipients. METHODS: Phase II, open-label,
single-arm, single-center, prospective pilot pharmacokinetic study. Study
population comprised 20 stable LT recipients receiving ODT, mean age 55.9 years
(range, 38-67 years), 13 (65%) men. Patients were switched to LCPT in a 1:0.7
(mg/mg) conversion dose. Follow-up was 6 months, and cystic fibrosis patients
were excluded. Two 24-hour pharmacokinetic profiles were obtained for each
patient, the first on day -14 and the second on day +14 after switching to LCPT.
Pharmacokinetic parameters and safety were compared. RESULTS: Mean (SD) area
under the concentration-time curve from 0 to 24 hours was 253.97 (61.90) ng/mL
per hour for ODT and 282.44 (68.2) ng/mL per hour for LCPT. Systemic exposure was
similar in both (Schuirmann two 1-sided test). Mean (SD) dose was 5.05 (1.67) mg
in ODT and 3.36 (1.03) mg in LCPT (P = 0.0002). Time to maximum concentration was
125 minutes for ODT and 325 minutes for LCPT (P < 0.001). Correlation between
area under the concentration-time curve from 0 to 24 hours and C24 was 0.896 (r)
for ODT and 0.893 (r) for LCPT. There were no differences in adverse effects. At
6 months, conversion dose was 1:0.59 (mg/mg) in patients with unchanged minimum
plasma concentration target levels. CONCLUSIONS: Switching from ODT to LCPT was
safe and well tolerated in stable LT recipients without cystic fibrosis. A
significantly lower dose of LCPT allows similar bioavailability. A conversion
ratio 1:0.6 could be enough to maintain similar target levels.
PMID- 29965951
TI - Measuring Patient Knowledge of Kidney Transplantation: an Initial Step to Close
the Knowledge Gap.
PMID- 29965952
TI - Measurement Characteristics of the Knowledge Assessment of Renal Transplantation
(KART).
AB - BACKGROUND: Kidney transplant is the best treatment for most end-stage renal
disease (ESRD) patients, but proportionally few ESRD patients receive kidney
transplant. To make an informed choice about whether to pursue kidney transplant,
patients must be knowledgeable of its risks and benefits. To reliably and validly
measure ESRD patients' kidney transplant knowledge, rigorously tested measures
are required. This paper describes the development and psychometric testing of
the Knowledge Assessment of Renal Transplantation (KART). METHODS: We
administered 17 transplant knowledge items to a sample of 1,294 ESRD patients.
Item characteristics and scale scores were estimated using an item response
theory (IRT) graded response model. Construct validity was tested by examining
differences in scale scores between patients who had spent < 1 and > 1 hour
receiving various types of transplant education. RESULTS: IRT modelling suggested
that 15 items should be retained for the KART. This scale had a marginal
reliability of 0.75 and evidenced acceptable reliability (>0.70) across most of
its range. Construct validity was supported by the KART's ability to distinguish
patients who had spent < 1 and > 1 hour receiving different types of kidney
transplant education, including talking to doctors/medical staff [effect size
(ES) = 0.61; p<0.001], reading brochures (ES = 0.45; p<0.001), browsing the
internet (ES = 0.56; p<0.001), and watching videos (ES = 0.56; p<0.001).
CONCLUSIONS: The final 15-item KART can be used to determine the kidney
transplant knowledge levels of ESRD patients and plan appropriate interventions
to ensure informed transplant decision-making occurs.
PMID- 29965953
TI - Efficient B cell Depletion With Rituximab Despite Massive Proteinuria.
PMID- 29965954
TI - Comparison of two Luminex Single-Antigen bead flow cytometry assays for detection
of Donor Specific Antibodies after renal transplantation.
AB - BACKGROUND: Defining the clinical relevance of Donor Specific HLA antibodies
(DSA) detection by Luminex Single Antigen (LSA) flow beads assay is critical in
monitoring posttransplant outcome. METHODS: Sera of kidney transplanted patients
were tested by LSA1 and LSA2 with One Lambda Labscreen (test 1) and Immucor
Lifecodes (test 2), at the time of a graft biopsy. The first group (G1, n=50) had
a biopsy highly suggestive of humoral rejection and the second (G2, n=50) had no
criteria of rejection. Positivity criteria for DSA was MFI >500 for test 1, while
specificity assignation respected provider's recommendations for test 2. RESULTS:
In G1, we identified at least 1 DSA in 44 patients with test 1, and in 39
patients with test 2. In G2, test 1 identified at least 1 DSA in 16 patients
(32%) and test 2 in 7 patients (14 %). Sensitivity and specificity for ABMR
diagnosis was 88% and 68% respectively with One Lambda, and 78% and 86%
respectively with Immucor. Correlation and agreement were found in class I and II
between intensity parameters of the 2 manufacturers. The use of the sum of the
intensity of DSA (sDSA) improved the sensitivity and specificity of the 2 tests.
CONCLUSIONS: We report the first comparative study of the 2 Luminex assays
available for detecting DSA in the post kidney transplant setting. Although there
is a good correlation and reliability between the 2 assays, significant
differences exist. Positivity criteria for DSA determination differ and
interpretation should take these specificities into account.
PMID- 29965955
TI - Quantifying the Effect of Transplanting Older Donor Livers Into Younger
Recipients: The Need for Donor-recipient Age Matching.
AB - BACKGROUND: Increasing recipient and donor age are independently associated with
survival after liver transplantation (LT). Whether donor age differentially
impacts post-LT outcomes based on recipient age is unknown. METHODS: This was a
retrospective cohort study using Organ Procurement and Transplantation Network
data. All adult deceased-donor, single organ, primary LTs from 2002 to 2015 were
included. Donor and recipient age were categorized as younger than 40 years, 40
to 59 years, and 60 years or older. Mixed-effects survival analysis evaluated the
risk of graft failure and death according to the interaction of donor and
recipient age categories. RESULTS: Of 63 628 LTs, 6.6% were in recipients younger
than 40 years, of which 51.4% used an age-matched donor younger than 40 years.
There was a significant among-center variability unrelated to United Network for
Organ Sharing region in the use of older organs in young recipients, ranging from
0% to 25% or greater (overall center median, 9.7%; interquartile range, 5.4
16.5%). There was a significant interaction between donor and recipient age (P <
0.05) such that the impact of older donor age was more pronounced in younger
recipients. Transplanting livers from donors aged 40 to 59 years and 60 years or
older was associated with worse graft survival in recipients younger than 40
years, but there was no difference based on donor age in recipients 60 years or
older. CONCLUSIONS: There is a differential impact of using older donors in
younger recipients than that in older recipients. Given their longer expected
post-LT survival and the ethical imperative to maximize utilization of the scarce
resource of transplantable livers, efforts should be made to allocate the highest
quality organs to those most likely to derive lasting benefit.
PMID- 29965956
TI - Early Detection of Chronic Asymptomatic Chagas Infection.
AB - Chagas disease, also known as American trypanosomiasis, is a chronic and systemic
parasitic infection which has become a serious epidemiological problem not only
in endemic regions (Latin America), but also in non-endemic ones like North
America, Europe, and Oceania. Subjects with the indeterminate chagasic form
(ICF), a chronic asymptomatic disease stage, are the main sources of non
vectorial dissemination through blood transfusion, organ transplantation, and
congenital transmission. It has been suggested that 94% of urban infections can
be explained by these subjects. Under this scenario, the availability of simple
and effective screening methods for ICF detection becomes crucial for both
prevention of disease propagation and detection of clinical stages. Recently, a
new non-invasive method has been proposed for ICF detection. It is based on
surface high-resolution ECG and it could be easily adopted and included in modern
ECG devices, overcoming the limitations of serological-based tests. The proposed
method shows accuracy for early ICF screening, thus improving prognosis by
defining the clinical stages and allowing appropriate and effective treatment.
PMID- 29965957
TI - Diagnosis and impact of neuropathic pain in leprosy patients in Nepal after
completion of multidrug therapy.
AB - OBJECTIVES: Neuropathic pain (NP) can occur as a chronic complication of leprosy
neuropathy. NP epidemiology and its impact on patients have not been well
documented. This study investigates NP prevalence and impact in the years after
patients are declared "released from treatment" (RFT) following multidrug therapy
(MDT) completion. METHODS: In this cross-sectional study, 85 RFT patients were
recruited within leprosy referral services in Nepal. The Douleur Neuropathique 4
Questionnaire (DN4) was used to screen for NP. Pain severity, impacts on
patients' daily activities and mental health were measured by using the Brief
Pain Inventory (BPI), Screening of Activity Limitation and Safety Awareness
(SALSA), and General Health Questionnaire-12 (GHQ-12) respectively. RESULTS: 96%
surveyed had been treated for multibacillary leprosy. 44 (52%) complained of pain
of which 30 (68%) were diagnosed with NP. NP was not associated with age, gender,
or presence of skin lesions or nerve symptoms at leprosy diagnosis. 70% of
patients with NP had either history of or ongoing reactions and 47% had grade 2
disability. Nerve tenderness (p = 0.023) and current reactions (p = 0.018) were
significant risk factors for NP. Patients with NP suffered significantly higher
intensity pain (p = 0.023) and daily life interference (p = 0.003) and were more
likely to have moderate to extreme daily activity limitations (p = 0.005). 13
(43%) exhibited psychological distress, and medications only reduced moderate
degree (50-60%) of pain. CONCLUSIONS: In our study, 35% of RFT patients had
ongoing NP. Risk factors include nerve tenderness and reaction. They suffer from
more daily life interference and psychological distress. Leprosy patient care
should include recognition and management of NP.
PMID- 29965960
TI - Strength in numbers: Collaborative science for new experimental model systems.
AB - Our current understanding of biology is heavily based on a small number of
genetically tractable model organisms. Most eukaryotic phyla lack such
experimental models, and this limits our ability to explore the molecular
mechanisms that ultimately define their biology, ecology, and diversity. In
particular, marine protists suffer from a paucity of model organisms despite
playing critical roles in global nutrient cycles, food webs, and climate. To
address this deficit, an initiative was launched in 2015 to foster the
development of ecologically and taxonomically diverse marine protist genetic
models. The development of new models faces many barriers, some technical and
others institutional, and this often discourages the risky, long-term effort that
may be required. To lower these barriers and tackle the complexity of this
effort, a highly collaborative community-based approach was taken. Herein, we
describe this approach, the advances achieved, and the lessons learned by
participants in this novel community-based model for research.
PMID- 29965958
TI - Variation in competence for ZIKV transmission by Aedes aegypti and Aedes
albopictus in Mexico.
AB - BACKGROUND: ZIKV is a new addition to the arboviruses circulating in the New
World, with more than 1 million cases since its introduction in 2015. A growing
number of studies have reported vector competence (VC) of Aedes mosquitoes from
several areas of the world for ZIKV transmission. Some studies have used New
World mosquitoes from disparate regions and concluded that these have a variable
but relatively low competence for the Asian lineage of ZIKV.
METHODOLOGY/PRINCIPAL FINDINGS: Ten Aedes aegypti (L) and three Ae. albopictus
(Skuse) collections made in 2016 from throughout Mexico were analyzed for ZIKV
(PRVABC59-Asian lineage) VC. Mexican Ae. aegypti had high rates of midgut
infection (MIR), dissemination (DIR) and salivary gland infection (SGIR) but low
to moderate transmission rates (TR). It is unclear whether this low TR was due to
heritable salivary gland escape barriers or to underestimating the amount of
virus in saliva due to the loss of virus during filtering and random losses on
surfaces when working with small volumes. VC varied among collections, geographic
regions and whether the collection was made north or south of the Neovolcanic
axis (NVA). The four rates were consistently lower in northeastern Mexico,
highest in collections along the Pacific coast and intermediate in the Yucatan.
All rates were lowest north of the NVA. It was difficult to assess VC in Ae.
albopictus because rates varied depending upon the number of generations in the
laboratory. CONCLUSIONS/SIGNIFICANCE: Mexican Ae. aegypti and Ae. albopictus are
competent vectors of ZIKV. There is however large variance in vector competence
among geographic sites and regions. At 14 days post infection, TR varied from 8
51% in Ae. aegypti and from 2-26% in Ae. albopictus.
PMID- 29965959
TI - RecQ helicases in the malaria parasite Plasmodium falciparum affect genome
stability, gene expression patterns and DNA replication dynamics.
AB - The malaria parasite Plasmodium falciparum has evolved an unusual genome
structure. The majority of the genome is relatively stable, with mutation rates
similar to most eukaryotic species. However, some regions are very unstable with
high recombination rates, driving the generation of new immune evasion-associated
var genes. The molecular factors controlling the inconsistent stability of this
genome are not known. Here we studied the roles of the two putative RecQ
helicases in P. falciparum, PfBLM and PfWRN. When PfWRN was knocked down,
recombination rates increased four-fold, generating chromosomal abnormalities, a
high rate of chimeric var genes and many microindels, particularly in known
'fragile sites'. This is the first identification of a gene involved in
suppressing recombination and maintaining genome stability in Plasmodium. By
contrast, no change in mutation rate appeared when the second RecQ helicase,
PfBLM, was mutated. At the transcriptional level, however, both helicases
evidently modulate the transcription of large cohorts of genes, with several
hundred genes-including a large proportion of vars-showing deregulated expression
in each RecQ mutant. Aberrant processing of stalled replication forks is a
possible mechanism underlying elevated mutation rates and this was assessed by
measuring DNA replication dynamics in the RecQ mutant lines. Replication forks
moved slowly and stalled at elevated rates in both mutants, confirming that RecQ
helicases are required for efficient DNA replication. Overall, this work
identifies the Plasmodium RecQ helicases as major players in DNA replication,
antigenic diversification and genome stability in the most lethal human malaria
parasite, with important implications for genome evolution in this pathogen.
PMID- 29965961
TI - Domestic animals infected with Mycobacterium ulcerans-Implications for
transmission to humans.
AB - BACKGROUND: The environmental pathogen, Mycobacterium ulcerans (MU) can infect
both humans and animals and cause Buruli ulcer (BU) disease. However, its mode(s)
of transmission from the colonized environment to human/animal hosts remain
unclear. In Australia, MU can infect both wildlife and domestic mammals. Till
date, BU-like lesions have only been reported in wildlife in Africa. This
warrants a thorough assessment of possible MU in domestic animals in Africa.
Here, we screened roaming domesticated animals that share the human microhabitat
in two different BU endemic sites, Sedje-Denou in Benin and Akonolinga in
Cameroon, for MU lesions. METHODOLOGY/PRINCIPAL FINDINGS: We screened roaming
mammals and birds across 3 endemic villages of Sedje-Denou in Southern Benin and
6 endemic villages of Akonolinga in Cameroon. After approval from relevant
authorities, specimens (wound swabs and tissue fragments) were collected from
animals with open or active lesion and systematically screened to detect the
presence of MU though the diagnostic DNA targets IS2404, IS2606 and KR-B. Out of
397 animals surveyed in Akonolinga, 44 (11.08%) carried skin lesions and all were
negative for MU DNA. For Sedje-Denou, only 25 (6.93%) out of 361 animals surveyed
carried external skin lesions of which 2 (8%) were positive for MU DNA targets.
These MU infected lesions were found in two different villages on a goat
(abdominal part) and on a dog (nape area of the neck). Source-tracking of MU
isolates within infected animal lesions was performed using VNTR genotyping and
further confirmed with sequencing. One MU VNTR genotype (Z) was successfully
typed from the goat lesion. The evolutionary history inferred from sequenced data
revealed a clustering of animal MU isolates within isolates from human lesions.
CONCLUSION/SIGNIFICANCE: This study describes the first report of two MU infected
lesions in domestic animals in Africa. Their DNA sequence analyses show close
relationship to isolates from human cases. It suggests that MU infection should
be suspected in domestic hosts and these could play a role in transmission. The
findings further support the hypothesis that MU is a ubiquitous environmental
pathogen found in endemic areas, and probably involved in a multiple transmission
pathway.
PMID- 29965962
TI - A dual regulation mechanism of histidine kinase CheA identified by combining
network-dynamics modeling and system-level input-output data.
AB - It is challenging to decipher molecular mechanisms in biological systems from
system-level input-output data, especially for complex processes that involve
interactions among multiple components. We addressed this general problem for the
bacterial histidine kinase CheA, the activity of which is regulated in chemotaxis
signaling complexes by bacterial chemoreceptors. We developed a general network
model to describe the dynamics of the system, treating the receptor complex with
coupling protein CheW and the P3P4P5 domains of kinase CheA as a regulated enzyme
with two substrates, ATP and P1, the phosphoryl-accepting domain of CheA. Our
simple network model allowed us to search hypothesis space systematically. For
different and progressively more complex regulation schemes, we fit our models to
a large set of input-output data with the aim of identifying the simplest
possible regulation mechanisms consistent with the data. Our modeling and
analysis revealed novel dual regulation mechanisms in which receptor activity
regulated ATP binding plus one other process, either P1 binding or phosphoryl
transfer between P1 and ATP. Strikingly, in our models receptor control affected
the kinetic rate constants of substrate association and dissociation equally and
thus did not alter the respective equilibrium constants. We suggest experiments
that could distinguish between the two dual-regulation mechanisms. This systems
biology approach of combining modeling and a large input-output dataset should be
applicable for studying other complex biological processes.
PMID- 29965964
TI - Correction: The population genetics of human disease: The case of recessive,
lethal mutations.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1006915.].
PMID- 29965963
TI - Integrated morbidity mapping of lymphatic filariasis and podoconiosis cases in 20
co-endemic districts of Ethiopia.
AB - BACKGROUND: Lymphatic filariasis (LF) and podoconiosis are neglected tropical
diseases (NTDs) that pose a significant physical, social and economic burden to
endemic communities. Patients affected by the clinical conditions of LF
(lymphoedema and hydrocoele) and podoconiosis (lymphoedema) need access to
morbidity management and disability prevention (MMDP) services. Clear estimates
of the number and location of these patients are essential to the efficient and
equitable implementation of MMDP services for both diseases.
METHODOLOGY/PRINCIPLE FINDINGS: A community-based cross-sectional study was
conducted in Ethiopia using the Health Extension Worker (HEW) network to identify
all cases of lymphoedema and hydrocoele in 20 woredas (districts) co-endemic for
LF and podoconiosis. A total of 612 trained HEWs and 40 supervisors from 20
districts identified 26,123 cases of clinical morbidity. Of these, 24,908 (95.3%)
reported cases had leg lymphoedema only, 751 (2.9%) had hydrocoele, 387 (1.5%)
had both leg lymphoedema and hydrocoele, and 77 (0.3%) cases had breast
lymphoedema. Of those reporting leg lymphoedema, 89.3% reported bilateral
lymphoedema. Older age groups were more likely to have a severe stage of disease,
have bilateral lymphoedema and to have experienced an acute attack in the last
six months. CONCLUSIONS/SIGNIFICANCE: This study represents the first community
wide, integrated clinical case mapping of both LF and podoconiosis in Ethiopia.
It highlights the high number of cases, particularly of leg lymphoedema that
could be attributed to either of these diseases. This key clinical information
will assist and guide the allocation of resources to where they are needed most.
PMID- 29965965
TI - Brain-computer interface use is a skill that user and system acquire together.
AB - A brain-computer interface (BCI) is a computer-based system that acquires,
analyzes, and translates brain signals into output commands in real time.
Perdikis and colleagues demonstrate superior performance in a Cybathlon BCI race
using a system based on "three pillars": machine learning, user training, and
application. These results highlight the fact that BCI use is a learned skill and
not simply a matter of "mind reading."
PMID- 29965966
TI - Nonmonotonic recruitment of ventromedial prefrontal cortex during remote memory
recall.
AB - Systems-level consolidation refers to the time-dependent reorganisation of memory
traces in the neocortex, a process in which the ventromedial prefrontal cortex
(vmPFC) has been implicated. Capturing the precise temporal evolution of this
crucial process in humans has long proved elusive. Here, we used multivariate
methods and a longitudinal functional magnetic resonance imaging (fMRI) design to
detect, with high granularity, the extent to which autobiographical memories of
different ages were represented in vmPFC and how this changed over time. We
observed an unexpected time course of vmPFC recruitment during retrieval, rising
and falling around an initial peak of 8-12 months, before reengaging for older 2-
and 5-year-old memories. This pattern was replicated in 2 independent sets of
memories. Moreover, it was further replicated in a follow-up study 8 months later
with the same participants and memories, for which the individual memory
representations had undergone their hypothesised strengthening or weakening over
time. We conclude that the temporal engagement of vmPFC in memory retrieval seems
to be nonmonotonic, revealing a complex relationship between systems-level
consolidation and prefrontal cortex recruitment that is unaccounted for by
current theories.
PMID- 29965967
TI - Evaluation of safety and immunogenicity of a group A streptococcus vaccine
candidate (MJ8VAX) in a randomized clinical trial.
AB - BACKGROUND: Group A streptococcus (GAS) is a serious human pathogen that affects
people of different ages and socio-economic levels. Although vaccination is
potentially one of the most effective methods to control GAS infection and its
sequelae, few prototype vaccines have been investigated in humans. In this study,
we report the safety and immunogenicity of a novel acetylated peptide-protein
conjugate vaccine candidate MJ8VAX (J8-DT), when delivered intramuscularly to
healthy adults. METHODS: A randomized, double-blinded, controlled Phase I
clinical trial was conducted in 10 healthy adult participants. Participants were
randomized 4:1 to receive the vaccine candidate (N = 8) or placebo (N = 2). A
single dose of the vaccine candidate (MJ8VAX), contained 50 MUg of peptide
conjugate (J8-DT) adsorbed onto aluminium hydroxide and re-suspended in PBS in a
total volume of 0.5 mL. Safety of the vaccine candidate was assessed by
monitoring local and systemic adverse reactions following intramuscular
administration. The immunogenicity of the vaccine was assessed by measuring the
levels of peptide (anti-J8) and toxoid carrier (anti-DT)-specific antibodies in
serum samples. RESULTS: No serious adverse events were reported over 12 months of
study. A total of 13 adverse events (AEs) were recorded, two of which were
assessed to be associated with the vaccine. Both were mild in severity. No local
reactogenicity was recorded in any of the participants. MJ8VAX was shown to be
immunogenic, with increase in vaccine-specific antibodies in the participants who
received the vaccine. The maximum level of vaccine-specific antibodies was
detected at 28 days post immunization. The level of these antibodies decreased
with time during follow-up. Participants who received the vaccine also had a
corresponding increase in anti-DT serum antibodies. CONCLUSIONS: Intramuscular
administration of MJ8VAX was demonstrated to be safe and immunogenic. The
presence of DT in the vaccine formulation resulted in a boost in the level of
anti-DT antibodies. TRIAL REGISTRATION: ACTRN12613000030774.
PMID- 29965968
TI - Sexual behaviors, HIV knowledge, HIV testing attitudes and recent HIV testing
among female entertainment workers in Cambodia: A cross-sectional study.
AB - BACKGROUND: In Cambodian context, female entertainment workers (FEWs) are young
women working at establishments such as karaoke bars, restaurants, beer gardens
or massage parlors. FEWs may sell sex to male patrons and are considered a high
risk group for HIV. This study aimed to identify factors associated with recent
HIV testing among FEWs in Cambodia to inform future prevention activities.
METHODS: Data were collected in 2014 as part of the evaluation of a larger HIV
prevention project. A two-stage cluster sampling method was used to select
participants from Phnom Penh and Siem Reap for face-to-face interviews using a
structured questionnaire. A logistic regression model was constructed to identify
independent factors associated with recent HIV testing. RESULTS: Data were
collected from 667 FEWs with a mean age of 25.6 (SD = 5.5). Of total, 81.7%
reported ever having had an HIV test, and 52.8% had at least one test in the past
six months. After adjustment for other covariates, factors independently
associated with recent HIV testing included living in Phnom Penh (AOR = 2.17, 95%
CI = 1.43-3.28), having received HIV education in the past six months (AOR =
3.48, 95% CI = 2.35-5.15), disagreeing with a statement that 'I would rather not
know if I have HIV' (AOR = 2.15, 95% CI = 1.41-3.30), agreeing with a statement
that 'getting tested for HIV helps people feel better' (AOR = 0.32, 95% CI = 0.13
0.81) and not using a condom in the last sexual intercourse with a non-commercial
partner (AOR = 0.48, 95% CI = 0.26-0.88). CONCLUSIONS: FEWs with greater
knowledge and positive attitudes towards HIV testing got tested for HIV more
frequently than those with lesser knowledge and less positive attitudes. These
findings suggest that future interventions should focus on disseminating tailored
health messages around testing practices as well as specific topics such as
condom use with non-commercial partners.
PMID- 29965969
TI - Vitamin D status contributes to the antimicrobial activity of macrophages against
Mycobacterium leprae.
AB - BACKGROUND: The immune system depends on effector pathways to eliminate invading
pathogens from the host in vivo. Macrophages (MPhi) of the innate immune system
are armed with vitamin D-dependent antimicrobial responses to kill intracellular
microbes. However, how the physiological levels of vitamin D during MPhi
differentiation affect phenotype and function is unknown. METHODOLOGY/PRINCIPAL:
The human innate immune system consists of divergent MPhi subsets that serve
distinct functions in vivo. Both IL-15 and IL-10 induce MPhi differentiation, but
IL-15 induces primary human monocytes to differentiate into antimicrobial MPhi
(IL-15 MPhi) that robustly express the vitamin D pathway. However, how vitamin D
status alters IL-15 MPhi phenotype and function is unknown. In this study, we
found that adding 25-hydroxyvitamin D3 (25D3) during the IL-15 induced
differentiation of monocytes into MPhi increased the expression of the
antimicrobial peptide cathelicidin, including both CAMP mRNA and the encoded
protein cathelicidin in a dose-dependent manner. The presence of physiological
levels of 25D during differentiation of IL-15 MPhi led to a significant vitamin D
dependent antimicrobial response against intracellular Mycobacterium leprae but
did not change the phenotype or phagocytic function of these MPhi. These data
suggest that activation of the vitamin D pathway during IL-15 MPhi
differentiation augments the antimicrobial response against M. leprae infection.
CONCLUSIONS/SIGNIFICANCE: Our data demonstrates that the presence of vitamin D
during MPhi differentiation bestows the capacity to mount an antimicrobial
response against M. leprae.
PMID- 29965970
TI - Pathogen invasion and non-epizootic dynamics in Pacific newts in California over
the last century.
AB - Emerging infectious disease is a growing threat to global biodiversity. The
infectious disease chytridiomycosis, caused by the fungal pathogen
Batrachochytrium dendrobatidis (Bd) has led to the decline and extinction of
hundreds of amphibian species. Severe Bd-caused epizootics have been documented
in North, Central and South America-with many of the research focused on anurans.
California, where Bd-related epizootics and amphibian declines have been
reported, has some of the highest diversity of salamanders. After more than a
decade since the first known epizootic in California, little is known about Bd
disease dynamics in salamanders. Pacific newts (Genus: Taricha) are ideal study
species because of their abundance, wide geographic range, occurrence in both
aquatic and terrestrial habitats, and how little is known about Bd infection
dynamics for this group. We conducted a retrospective study to determine the
relationship between Pacific newts and the fungal pathogen. We tested 1895
specimens collected between 1889-2009 and found no evidence of Bd-infected
Pacific newts until the late 1940's. Although we estimate that Bd emerged in this
genus and rapidly spread geographically throughout California, we did not find
evidence for epizootic dynamics. Bd infection prevalence and intensity, two
measures commonly used to estimate dynamics, remained consistently low over time;
suggesting Pacific newts may not be highly susceptible. Also, we found the timing
of first Bd emergence in Pacific newts predate Bd emergence in other California
salamander species. In addition, we found several environmental and anthropogenic
factors correlated with Bd prevalence which may help explain Bd disease dynamics
in the genus Taricha. Pacific newts may be a reservoir species that signal
pathogen invasion into California salamanders, though further studies are needed.
PMID- 29965971
TI - The transverse four-chamber view for the assessment of atrial tissue deformation
in the fetus.
AB - AIMS: To determine if atrial tissue deformation (peak strain, PS) and time to
peak strain (TTPS) can be assessed in the fetus, with identification of best
echocardiographic plane. MATERIALS AND METHODS: Pulsed-wave tissue Doppler study
of a longitudinal and a transverse four-chamber view (FCV) in each of 20 healthy
fetuses. Determination of PS and TTPS in regions of interest (ROI), viz., lateral
walls of the right and left atria (RA, LA); comparison of values depending on
section plane, with results-based discussion of the physiology of fetal atrial
deformation and of possible clinical uses. RESULTS: PS and TTPS could be
determined on transverse FCV in 91% of subjects and in 61% on longitudinal FCV.
Transverse PS and TTPS were significantly higher than longitudinal (p = 0.0001).
Transverse PS was significantly higher in RA than in LA (26.9% vs. 17.3%, p =
0.034), and transverse TTPS was significantly shorter in RA than in LA (p =
0.034). CONCLUSION: Atrial radial PS and TTPS determinations are possible in the
fetus. The transverse FCV is best suited for these. The highest PS values and
shortest TTPS values are found in ROI representing the RA. Our findings may
contribute to detailed intrauterine assessment of atrial and ventricular
myocardial function.
PMID- 29965972
TI - Twenty-seven years of screening for Shiga toxin-producing Escherichia coli in a
university hospital. Brussels, Belgium, 1987-2014.
AB - OBJECTIVE: Since 1987 all fecal samples referred to the clinical microbiology
laboratory of the UZ Brussel were screened for the presence of Shiga toxin
producing E. coli (STEC). In this study all STEC strains isolated over a period
of 27 years (1987-2014) were reexamined to achieve deeper insight in the STEC
infections in our patient population. METHODS: A total of 606 STEC strains from
604 patients were subjected to molecular methods for shiga toxin (stx) subtyping,
detection of additional virulence genes, typing of the O-serogroups, and
phylogenetic relatedness assessment of STEC O157:H7/H-. RESULTS: Since the
introduction of PCR in 1991 the annual positivity rates varied between 1.1% and
2.7%. The isolation rate of STEC O157:H7/H- remained stable over the years while
the isolation rate of non-O157 serotypes increased, mainly since 2011. The
majority of the patients were children. Uncomplicated- and bloody diarrhea were
the most prevalent gastrointestinal manifestations (respectively 51.9% and
13.6%), 4.3% of the strains were related to the hemolytic uremic syndrome (HUS),
and 30.2% of the patients showed none of these symptoms. The strains were very
diverse; they belonged to 72 different O-serovars and all stx subtypes except
stx1d and stx2g were identified. Out of the 23 stx2f-positives one was associated
with HUS and one belonged to the E. albertii species. As seen in other studies,
the frequency of strains of the O157:H7/H- serotype and strains carrying stx2a,
eaeA and ehxA was higher in patients with HUS. CONCLUSIONS: The characteristics
and trends of STEC infection seen in our patient population are similar to those
noted in other countries. STEC infections in our hospital are mainly sporadic,
and a substantial portion of the patients were asymptomatic carriers. Human STEC
Stx2f infection was less rare than previously assumed and we report the first
Belgian STEC stx2f HUS case and stx2f positive E. albertii infection.
PMID- 29965973
TI - Long-term metabolic effects of malnutrition: Liver steatosis and insulin
resistance following early-life protein restriction.
AB - Early postnatal-life malnutrition remains prevalent globally, and about 45% of
all child deaths are linked to malnutrition. It is not clear whether survivors of
childhood malnutrition suffer from long-term metabolic effects, especially when
they are later in life exposed to a fat and carbohydrate rich obesogenic diet.
The lack of knowledge around this dietary "double burden" warrants studies to
understand the long-term consequences of children previously exposed to
malnutrition. We hypothesized that an early-life nutritional insult of low
protein consumption in mice would lead to long-term metabolic disturbances that
would exacerbate the development of diet-induced insulin resistance and non
alcoholic fatty liver disease (NAFLD). We investigated the effects of feeding a
low protein diet (4% wt/wt) immediately after weaning for four weeks and
subsequent feeding of a high carbohydrate high fat feeding for 16 weeks on
metabolic function and development of NAFLD. Mice exposed to early-life protein
restriction demonstrated a transient glucose intolerance upon recovery by regular
chow diet feeding. However, protein restriction after weaning in mice did not
exacerbate an obesogenic diet-induced insulin resistance or progression to NAFLD.
These data suggest that transient protein restriction in early-life does not
exacerbate an obesogenic diet-induced NAFLD and insulin resistance.
PMID- 29965974
TI - Differential expression and function of CAIX and CAXII in breast cancer: A
comparison between tumorgraft models and cells.
AB - Carbonic anhydrase IX (CAIX) and XII (CAXII) are transmembrane proteins that are
associated with cancer progression. We have previously described the catalytic
properties of CAIX in MDA-MB-231 breast cancer cells, a line of cells that were
derived from a patient with triple negative breast cancer. We chose this line
because CAIX expression in breast cancer is a marker of hypoxia and a
prognosticator for reduced survival. However, CAXII expression is associated with
better survival statistics than those patients with low CAXII expression. Yet
CAIX and CAXII have similar catalytic activities. Here we compare the potential
roles of CAIX and CAXII in the context of TNBC and estrogen receptor (ER)
positive breast cancer. In tumor graft models, we show that CAIX and CAXII
exhibit distinct expression patterns and non-overlapping. We find the same
pattern across a panel of TNBC and luminal breast cancer cell lines. This affords
an opportunity to compare directly CAIX and CAXII function. Our data suggest that
CAIX expression is associated with growth potentiation in the tumor graft model
and in a TNBC line using knockdown strategies and blocking activity with an
impermeant sulfonamide inhibitor, N-3500. CAXII was not associated with growth
potentiation. The catalytic activities of both CAIX and CAXII were sensitive to
inhibition by N-3500 and activated at low pH. However, pH titration of activity
in membrane ghosts revealed significant differences in the catalytic efficiency
and pKa values. These features provide evidence that CAIX is a more efficient
enzyme than CAXII at low pH and that CAIX shifts the equilibrium between CO2 and
bicarbonate in favor of CO2 production by consuming protons. This suggests that
in the acidic microenvironment of tumors, CAIX plays a role in stabilizing pH at
a value that favors cancer cell survival.
PMID- 29965975
TI - Use of the revised World Health Organization cluster survey methodology to
classify measles-rubella vaccination campaign coverage in 47 counties in Kenya,
2016.
AB - INTRODUCTION: To achieve measles elimination, two doses of measles-containing
vaccine (MCV) are provided through routine immunization services or vaccination
campaigns. In May 2016, Kenya conducted a measles-rubella (MR) vaccination
campaign targeting 19 million children aged 9 months-14 years, with a goal of
achieving >=95% coverage. We conducted a post-campaign cluster survey to estimate
national coverage and classify coverage in Kenya's 47 counties. METHODS: The
stratified multi-stage cluster survey included data from 20,011 children in 8,253
households sampled using the recently revised World Health Organization coverage
survey methodology (2015). Point estimates and 95% confidence intervals (95% CI)
of national campaign coverage were calculated, accounting for study design.
County vaccination coverage was classified as 'pass,' 'fail,' or 'intermediate,'
using one-sided hypothesis tests against a 95% threshold. RESULTS: Estimated
national MR campaign coverage was 95% (95% CI: 94%-96%). Coverage differed
significantly (p < 0.05) by child's school attendance, mother's education,
household wealth, and other factors. In classifying coverage, 20 counties passed
(>=95%), two failed (<95%), and 25 were intermediate (unable to classify either
way). Reported campaign awareness among caretakers was 92%. After the 2016 MR
campaign, an estimated 93% (95% CI: 92%-94%) of children aged 9 months to 14
years had received >=2 MCV doses; 6% (95% CI: 6%-7%) had 1 MCV dose; and 0.7%
(95% CI: 0.6%-0.9%) remained unvaccinated. CONCLUSIONS: Kenya reached the MR
campaign target of 95% vaccination coverage, representing a substantial
achievement towards increasing population immunity. High campaign awareness
reflected the comprehensive social mobilization strategy implemented in Kenya and
supports the importance of including strong communications platforms in future
vaccination campaigns. In counties with sub-optimal MR campaign coverage, further
efforts are needed to increase MCV coverage to achieve the national goal of
measles elimination by 2020.
PMID- 29965976
TI - Welfare effects of health insurance in Mexico: The case of Seguro Popular de
Salud.
AB - This study contributes with original empirical evidence on the distributional and
welfare effects of one of the most important health policies implemented by the
Mexican government in the last decade, the Seguro Popular de Salud (SPS). We
analyze the effect of SPS on households' welfare using a decomposable index that
considers insured and uninsured households' response to out-of-pocket (OOP)
payments using both social welfare weights and inequality aversion. The
disaggregation of the welfare index allows us to explore the heterogeneity of the
SPS impact on households' welfare. We applied propensity score matching to reduce
the self-selection bias of being SPS insured. Overall results suggest non
conclusive results of the impact of SPS on households' welfare. When we
disaggregated the welfare index by different sub-population groups, our results
suggest that households' beneficiaries of SPS with older adults or living in
larger cities are better protected against OOP health care payments than their
uninsured counterparts. However, no effect was found among SPS-insured households
living in rural and smaller cities, which is a result that could be attributed to
limited access to health resources in these regions. Scaling up health insurance
coverage is a necessary but not sufficient condition to ensure the protection of
SPS coverage against financial risks among the poor.
PMID- 29965977
TI - Numerical simulation of nanopost-guided self-organization dendritic architectures
using phase-field model.
AB - Self-organized dendritic architecture is of fundamental importance and its
application can be used in many natural and industrial processes. Nanopost arrays
are usually used in the applications of reflecting grating and changing the
material surface wettability. However, in recent research, it is found that
nanopost arrays can be fabricated as passive components to induce the dendritic
self-organizaed hierarchical architectures. Via this simplified Phase-Field based
finite element simulation, the surface dendritic self-organized architecture
morphology and expanding speed in the growing path can be controlled by nanopost
structures. In addition, nanopost array arrangement on the surface affects the
hierarchal architecture branching distribution. Finally, with an external applied
force introduced to the system, it enables the nanopost as an active component.
It is found that nanopost surroundings significantly impact the final
distribution of dendritic architectures which is qualitatively in agreement with
experiments and induce these dendritic architectures to form assigned character
patterns after the external driving forces are introduced into the system. This
novel study can fundamentally study the dynamic physics of dendritic self
organized architecutes provide an indicator for the development of smart self
organized architecture, and a great opportunity for the creation of large-scale
hierarchical structures.
PMID- 29965978
TI - Increased hydrophilic plasma bile acids are correlated with protection from
adiposity in skin-specific stearoyl-CoA desaturase-1 deficient mice.
AB - Stearoyl-CoA desaturase 1 (SCD1) catalyzes the rate limiting step in
monounsaturated fatty acid synthesis by inserting a double bond at the delta-9
position of long-chain fatty acids. SCD1 converts stearate (18:0) to oleate
(18:1n9) and palmitate (16:0) to palmitoleate (16:1n7), respectively. Mice with
global and skin-specific deletion (SKO) of SCD1 exhibit increased whole body
energy expenditure and protection against diet-induced adiposity, hepatic
steatosis, insulin sensitivity and glucose intolerance. The mechanisms that link
cutaneous lipid homeostasis with whole body energy balance are presently unknown.
In this study, we reveal that SKO mice demonstrate increased skin surface free
cholesterol, decreased circulating total cholesterol and increased taurine
conjugated and hydrophilic bile acids. Tauro-beta-muricholic acid, which is a
marker of extrahepatic bile acid synthesis, is significantly elevated in SKO
plasma. Bile acid signaling through the bile acid-specific receptor TGR5 is known
to be protective against obesity and metabolic disease; a phenotype that is
similar to SKO mice. We therefore examined TGR5 expression and its downstream
mediator, DIO2, in various tissues and found that both TGR5 and DIO2 expression
were significantly increased in brown adipose tissue. In sum, we suggest that
skin-derived bile acids are involved in the lean and metabolically healthy
phenotype of SKO mice.
PMID- 29965979
TI - Norovirus RNA in serum associated with increased fecal viral load in children:
Detection, quantification and molecular analysis.
AB - Worldwide, norovirus (NoV) is a major cause of acute gastroenteritis (AGE)
responsible for pandemics every ~3 years, and over 200,000 deaths per year, with
the majority in children from developing countries. We investigate the incidence
of NoV in children hospitalized with AGE from Belem, Para, Brazil, and also
correlated viral RNA levels in their blood and stool with clinical severity. For
this purpose, paired stool and serum samples were collected from 445 pediatric
patients, <=9 years between March 2012 and June 2015. Enzyme-linked immunosorbent
assay (EIA) was used to detect NoV in stool and reverse transcription
quantitative PCR (RT-qPCR) used to quantify NoV RNA levels in sera (RNAemia) and
in the positive stool. Positives samples were characterized by the partial ORF1/2
region sequence of viral genome. NoV antigen was detected in 24.3% (108/445) of
stool samples, with RNAemia also present in 20.4% (22/108). RNAemia and a high
stool viral load (>107 genome copies/gram of faeces) were associated with longer
hospitalizations. The prevalent genotypes were GII.4 Sydney_2012 (71.6%-58/81)
and New Orleans_2009 (6.2%-5/81) variants. Eight other genotypes belonging to GII
were detected and four of them were recombinant strains. All sera were
characterized as GII.4 and shared 100% similarity with their stool. The results
suggest that the dissemination of NoV to the blood stream is not uncommon and may
be related to increased faecal viral loads and disease severity.
PMID- 29965980
TI - The N-terminal region of photocleavable peptides that bind HLA-DR1 determines the
kinetics of fragment release.
AB - Major Histocompatibility Complex class II (MHC-II) molecules bind peptides and
present them to receptors on CD4+ T cells as part of the immune system's
surveillance of pathogens and malignancy. In the absence of peptide, MHC-II
equilibrates between peptide-receptive and peptide-averse conformations. The
conversion between these forms has been postulated to be important in regulating
cellular antigen presentation but has been difficult to study. In order to
generate the MHC-II molecule HLA-DR1 in the peptide-receptive form, we designed
and tested a series of photocleavable peptides that included the UV-sensitive 3
amino-3-(2-nitrophenyl)-propionate amino acid analog. They were intended to bind
tightly to the HLA-DR1 MHC molecule, but to generate low-affinity fragments after
UV exposure that would be released to yield HLA-DR1 in the peptide-receptive
conformation. We were able to identify photocleavable peptides that bound tightly
to HLA-DR1 and generated the peptide-receptive conformation after UV exposure.
However, slow release of photocleaved peptide fragments from the binding site
limited the rate of binding of an incoming labeled peptide and complicated
kinetic measurements of the individual steps of the overall peptide binding
reaction. Modification of the N-terminal region of the photocleavable peptide to
reduce MHC-II pocket or H-bonding interactions allowed for generation of the
peptide receptive form immediately after UV exposure with peptide fragments
neither retained within the site nor interfering with binding of an incoming
peptide. However this was achieved only at the expense of a substantial reduction
in overall peptide binding affinity, and these peptides had such weak interaction
with HLA-DR1 that they were easily exchanged by incoming peptide without UV
exposure. These results show that photocleavable peptides can be used to generate
peptide-receptive HLA-DR1 and to facilitate peptide exchange in generation of
specific peptide-MHC-II complexes, but that usage of these peptides for kinetic
studies can be constrained by slow fragment release.
PMID- 29965981
TI - Structure-activity study of furyl aryloxazole fluorescent probes for the
detection of singlet oxygen.
AB - In this study, we report the synthesis and the photochemical behavior of a series
of new "click-on" fluorescent probes designed to detect singlet oxygen. They
include a highly fluorescent chemical structure, an aryloxazole ring, linked to a
furan moiety operating as singlet oxygen trap. Their activity depends on both the
structure of the aryloxazole fluorophore and the electron-donating and electron
accepting properties of the substituents attached to the C-5 of the furan ring.
All probes are selectively oxidized by singlet oxygen to give a single
fluorescent product in methanol and produce negligible amounts of singlet oxygen
themselves by self-sensitization. The most promising dyad, (E)-2-(2-(5
methylfuran-2-yl)vinyl)naphtho[1,2-d]oxazole, FN-6, shows outstanding reactivity
and sensitivity: it traps singlet oxygen with a rate constant (5,8 +/- 0.1) x 107
M-1 s-1 and its fluorescence increases by a factor of 500 upon reaction. Analysis
of the dyads reactivity in terms of linear free energy relationships using the
modified Swain and Lupton parameter F and the Fukui condensed function for the
electrophilic attack, suggests that cycloaddition of singlet oxygen to the furan
ring is partially concerted and possibly involves an exciplex with a "more open"
structure than could be expected for a concerted cycloaddition.
PMID- 29965982
TI - Eucalyptus ash alters secondary protein conformation of human grey hair and
facilitates anthocyanin dyeing.
AB - Wood ashes infused with water have been traditionally used as hair cosmetics, but
little or no research has examined the effects of ash on human hair. This study
investigated the effect of eucalyptus ash on the structure and morphology of
excised human grey hair and its potential use as a pretreatment in natural hair
dyeing using anthocyanins extracted from purple cops of Zea mays. Tensile
characteristics and surface morphology of ash-pretreated hair was monitored by
texture analysis, scanning electron microscopy and atomic force microscopy. The
biochemical characteristics of ash-treated hair were analyzed by synchrotron
radiation-FTIR and sulfur K-edge X-ray absorption near edge. Dyeing with
anthocyanins was analyzed by Lab color scale and adsorption of anthocyanins. Ash
treated hair was elastically and plastically deformed with microscopic
alterations to the ridges of the cuticle cells, similar to ammonia-treated hair.
The ash extract significantly changed the relative proportion of alpha-helices in
the cuticle and cortex layers (p < 0.05), but did not affect the interaction of S
bonds with neighboring atoms (p > 0.05). Ash-treated hair showed significantly
enhanced adsorption of anthocyanins (p < 0.05) which changed the color of the
grey hair. The alteration of secondary proteins in the cuticle and cortex layers
of the grey hair by ash extract pre-treatment, enhanced anthocyanin adsorption.
The eucalyptus ash could potentially be useful as a natural hair dyeing pre
treatment.
PMID- 29965983
TI - The research topic landscape in the literature of social class and inequality.
AB - The literature of social class and inequality is not only diverse and rich in
sight, but also complex and fragmented in structure. This article seeks to map
the topic landscape of the field and identify salient development trajectories
over time. We apply the Latent Dirichlet Allocation topic modeling technique to
extract 25 distinct topics from 14,038 SSCI articles published between 1956 to
2017. We classified three topics as "hot", eight as "stable" and 14 as "cold",
based on each topic's idiosyncratic temporal trajectory. We also listed the three
most cited references and the three most popular journal outlets per topic. Our
research suggests that future effort may be devoted to Topics "urban
inequalities, corporate social responsibility and public policy in connected
capitalism", "education and social inequality", "community health intervention
and social inequality in multicultural contexts" and "income inequality, labor
market reform and industrial relations".
PMID- 29965984
TI - Emotional cues from expressive behavior of women and men with Parkinson's
disease.
AB - OBJECTIVE: Emotional experience of people with Parkinson's disease is prone to
being misunderstood by observers and even healthcare practitioners, which affects
treatment effectiveness and makes clients suffer distress in their social lives.
This study was designed to identify reliable emotional cues from expressive
behavior in women and men with Parkinson's disease. METHOD: Videotaped expressive
behavior of 96 participants during an interview of discussing enjoyable events
was rated using the Interpersonal Communication Rating Protocol. Indices from
emotional measures were represented in three components. Correlational analyses
between expressive behavior domains and emotional components were conducted for
the total sample and by gender separately. RESULTS: More gross motor expressivity
and smiling/laughing indicated more positive affect in the total sample. Less
conversational engagement indicated more negative affect in women. However, women
with more negative affect and depression appeared to smile and laugh more.
CONCLUSION: This study identified reliable cues from expressive behavior that
could be used for assessment of emotional experience in people with Parkinson's
disease. For women, because smiling/laughing may convey two possible meanings,
that is, more positive and more negative affect, this cue needs to be interpreted
cautiously and be used for detecting the intensity, not the type, of emotional
experience. Healthcare practitioners should be sensitive to valid cues to make an
accurate evaluation of emotion in people with Parkinson's disease.
PMID- 29965985
TI - Cyc8p and Tup1p transcription regulators antagonistically regulate Flo11p
expression and complexity of yeast colony biofilms.
AB - Yeast biofilms are complex multicellular structures, in which the cells are well
protected against drugs and other treatments and thus highly resistant to
antifungal therapies. Colony biofilms represent an ideal system for studying
molecular mechanisms and regulations involved in development and internal
organization of biofilm structure as well as those that are involved in fungal
domestication. We have identified here antagonistic functional interactions
between transcriptional regulators Cyc8p and Tup1p that modulate the life-style
of natural S. cerevisiae strains between biofilm and domesticated mode. Herein,
strains with different levels of Cyc8p and Tup1p regulators were constructed,
analyzed for processes involved in colony biofilm development and used in the
identification of modes of regulation of Flo11p, a key adhesin in biofilm
formation. Our data show that Tup1p and Cyc8p regulate biofilm formation in the
opposite manner, being positive and negative regulators of colony complexity,
cell-cell interaction and adhesion to surfaces. Notably, in-depth analysis of
regulation of expression of Flo11p adhesin revealed that Cyc8p itself is the key
repressor of FLO11 expression, whereas Tup1p counteracts Cyc8p's repressive
function and, in addition, counters Flo11p degradation by an extracellular
protease. Interestingly, the opposing actions of Tup1p and Cyc8p concern
processes crucial to the biofilm mode of yeast multicellularity, whereas other
multicellular processes such as cell flocculation are co-repressed by both
regulators. This study provides insight into the mechanisms regulating complexity
of the biofilm lifestyle of yeast grown on semisolid surfaces.
PMID- 29965986
TI - The presence of genetic risk variants within PTPN2 and PTPN22 is associated with
intestinal microbiota alterations in Swiss IBD cohort patients.
AB - BACKGROUND: Genetic risk factors, intestinal microbiota and a dysregulated immune
system contribute to the pathogenesis of inflammatory bowel disease (IBD). We
have previously demonstrated that dysfunction of protein tyrosine phosphatase non
receptor type 2 (PTPN2) and PTPN22 contributes to alterations of intestinal
microbiota and the onset of chronic intestinal inflammation in vivo. Here, we
investigated the influence of PTPN2 and PTPN22 gene variants on intestinal
microbiota composition in IBD patients. METHODS: Bacterial DNA from mucosa
associated samples of 75 CD and 57 UC patients were sequenced using 16S rRNA
sequencing approach. Microbial analysis, including alpha diversity, beta
diversity and taxonomical analysis by comparing to PTPN2 (rs1893217) and PTPN22
(rs2476601) genotypes was performed in QIIME, the phyloseq R package and MaAsLin
pipeline. RESULTS: In PTPN2 variant UC patients, we detected an increase in
relative abundance of unassigned genera from Clostridiales and Lachnospiraceae
families and reduction of Roseburia when compared to PTPN2 wild-type (WT)
patients. Ruminoccocus was increased in PTPN22 variant UC patients. In CD
patients with severe disease course, Faecalibacterium, Bilophila, Coprococcus,
unclassified Erysipelotrichaeceae, unassigned genera from Clostridiales and
Ruminococcaceae families were reduced and Bacteroides were increased in PTPN2 WT
carriers, while Faecalibacterium, Bilophila, Coprococcus, and
Erysipelotrichaeceae were reduced in PTPN22 WT patients when compared to patients
with mild disease. In UC patients with severe disease, relative abundance of
Lachnobacterium was reduced in PTPN2 and PTPN22 WT patients, Dorea was increased
in samples from PTPN22 WT carriers and an unassigned genus from Ruminococcaceae
gen. was increased in patients with PTPN2 variant genotype. CONCLUSIONS: We
identified that IBD-associated genetic risk variants, disease severity and the
interaction of these factors are related to significant alterations in intestinal
microbiota composition of IBD patients.
PMID- 29965987
TI - Impact of schistosome infection on long-term HIV/AIDS outcomes.
AB - BACKGROUND: Africa bears the burden of approximately 70% of global HIV infections
and 90% of global schistosome infections. We sought to investigate the impact of
schistosome infection at the time of HIV-1 seroconversion on the speed of HIV-1
disease progression, as measured by the outcome CD4+ T-cell (CD4) counts <350
cells/MUL and/or death. We hypothesized that people who had been infected with
Schistosoma spp. at the time they acquired HIV-1 infection would have impaired
antiviral immune response, thus leading them to progress twice as fast to a CD4
count less than 350 cells/MUL or death than would people who had been free of
schistosomes at time of HIV-1 seroconversion. METHODS AND PRINCIPAL FINDINGS: We
conducted a longitudinal study in Tanzania from 2006 to 2017 using stored blood
spot samples, demographic surveillance and sero-survey data from the community,
and a review of clinical charts. A competing risk analysis was performed to look
at the difference in time to reaching CD4 counts < 350 cells/MUL and/or death in
HIV-1-infected people who were infected versus not infected with Schistosoma spp.
at time of HIV-1 seroconversion. We found an 82% reduction in risk of reaching
the outcome in seroconverters who had been infected with Schistosoma (subHazard
Ratio = 0.18[0.068,0.50], p = 0.001) after adjusting for age, occupation, clinic
attendance and time-dependent covariates. CONCLUSIONS: Our study demonstrates
that people with schistosome infection at the time of HIV-seroconversion develop
adverse HIV outcomes more slowly than those without. The findings are contrary to
our original hypothesis. Our current longitudinal findings suggest complex
interactions between HIV-1 and schistosome co-infections that may be modulated
over time. We urge new immunological studies to investigate the long-term impact
of schistosome infection on HIV-1 viral load and CD4 counts as well as related
immunologic pathways.
PMID- 29965988
TI - Thermostabilization and purification of the human dopamine transporter (hDAT) in
an inhibitor and allosteric ligand bound conformation.
AB - The human dopamine transporter (hDAT) plays a major role in dopamine homeostasis
and regulation of neurotransmission by clearing dopamine from the extracellular
space using secondary active transport. Dopamine is an essential monoamine
chemical messenger that regulates reward seeking behavior, motor control,
hormonal release, and emotional response in humans. Psychostimulants such as
cocaine primarily target the central binding site of hDAT and lock the
transporter in an outward-facing conformation, thereby inhibiting dopamine
reuptake. The inhibition of dopamine reuptake leads to accumulation of dopamine
in the synapse causing heightened signaling. In addition, hDAT is implicated in
various neurological disorders and disease-associated neurodegeneration. Despite
its significance, the structural studies of hDAT have proven difficult.
Instability of hDAT in detergent micelles has been a limiting factor in its
successful biochemical, biophysical, and structural characterization. To overcome
this hurdle, we identified ligands that stabilize hDAT in detergent micelles. We
then screened ~200 single residue mutants of hDAT using a high-throughput
scintillation proximity assay and identified a thermostable variant (I248Y). Here
we report a robust strategy to overexpress and successfully purify a thermostable
variant of hDAT in an inhibitor and allosteric ligand bound conformation.
PMID- 29965989
TI - Induction of labor after one previous Cesarean section in women with an
unfavorable cervix: A retrospective cohort study.
AB - OBJECTIVE: Uterine rupture is a well-known but unusual complication in vaginal
deliveries with a Cesarean section in the history. The risk of uterine rupture is
at least two-fold when labor is induced. In Sweden, women are allowed to deliver
vaginally after one previous Cesarean section, regardless if labor starts
spontaneously or is induced. The aim of the study is to compare the proportion of
uterine ruptures between the three methods (balloon catheter, Minprostin(r) and
Cytotec(r)) for induction of labor in women with an unfavorable cervix and one
previous Cesarean section. MATERIAL AND METHODS: Retrospective cohort study of
all women with one previous Cesarean section and induction of labor with an
unfavorable cervix at the four largest clinics in Stockholm during 2012-2015.
Inclusion criteria: Women with a previous Cesarean section and induction of labor
with a viable fetus, cephalic presentation, singleton, at >=34 w, (n = 910).
RESULTS: 3.0% (27/910) of the women with induction of labor had a uterine
rupture, 91% of them had no previous vaginal delivery. The proportion of uterine
ruptures was 2.0% (6/295) with orally administrated Cytotec(r), 2.1% (7/335) with
balloon catheter and 5.0% (14/ 281) when Minprostin(r) was used. CONCLUSIONS: No
difference in the proportion of uterine ruptures was shown when orally
administrated Cytotec(r) and balloon catheter were compared (p = 0.64). Orally
administrated Cytotec(r) and balloon catheter give a high success rate of vaginal
deliveries (almost 70%) despite an unfavorable cervix.
PMID- 29965990
TI - Patients experiences of self-management and strategies for dealing with chronic
conditions in rural Malawi.
AB - BACKGROUND: The high burden of chronic communicable diseases such as HIV/AIDS,
and an escalating rise of non-communicable diseases (NCDs) in Malawi and other
sub-Saharan African countries, calls for a shift in how health care services are
designed and delivered. Patient-centred care and patient self-management are
critical elements in chronic care, and are advocated as universal strategies. In
sub-Saharan Africa, there is need for more evidence around the practice of
patient self-management, and how to best support patients with chronic conditions
in the African context. Our study explored self-management practices of patients
with different chronic conditions, and their strategies to overcome care
challenges in a resource-constrained setting in Malawi. METHODS: This is
primarily a qualitative study, involving patients with different chronic
conditions from one rural district in Malawi. Data are drawn from semi-structured
questions of a survey with 129 patients (from the third of four-part data
collection series), 14 in-depth interviews, and four focus-group discussions with
patients (n = 31 respondents). A framework approach was used for qualitative
analysis, and descriptive statistical analysis was performed on survey data.
RESULTS: Patients demonstrated ability to self-manage their conditions, though
this varied between conditions, and was influenced by individual and external
factors. Factors included: 1) ability to acquire appropriate disease knowledge;
2) poverty level; 3) the presence of support from family caregivers and community
based support initiatives; 4) the nature of one's social relations; and 5) the
ability to deal with stressors and stigma. NCD and HIV comorbid patients were
more disadvantaged in their access to care, as they experienced frequent drug
stock-outs and incurred additional costs when referred. These barriers
contributed to delayed care, poorer treatment adherence, and likelihood of poorer
treatment outcomes. Patients proved resourceful and made adjustments in the face
of (multiple) care challenges. CONCLUSION: Our findings complement other research
on self-management experiences in chronically ill patients with its analysis on
factors and barriers that influence patient self-management capacity in a
resource-constrained setting. We recommend expanding current peer-patient and
support group initiatives to patients with NCDs, and further investments in the
decentralisation of integrated health services to primary care level in Malawi.
PMID- 29965991
TI - Prehospital ultrasound-guided nerve blocks improve reduction-feasibility of
dislocated extremity injuries compared to systemic analgesia. A randomized
controlled trial.
AB - BACKGROUND: Out-of-hospital analgosedation in trauma patients is challenging for
emergency physicians due to associated complications. We compared peripheral
nerve block (PNB) with analgosedation (AS) as an analgetic approach for patients
with isolated extremity injury, assuming that prehospital required medical
interventions (e.g. reduction, splinting of dislocation injury) using PNB are
less painful and more feasible compared to AS. METHODS: Thirty patients (aged 18
or older) were randomized to receive either ultrasound-guided PNB (10 mL
prilocaine 1%, 10 mL ropivacaine 0.2%) or analgosedation (midazolam combined with
s-ketamine or with fentanyl). Reduction-feasibility was classified (easy,
intermediate, impossible) and pain scores were assessed using numeric rating
scales (NRS 0-10). RESULTS: Eighteen patients were included in the PNB-group and
twelve in the AS-group; 15 and 9 patients, respectively, suffered dislocation
injury. In the PNB-group, reduction was more feasible (easy: 80.0%, impossible:
20.0%) compared to the AS-group (easy: 22.2%, intermediate: 22.2%, impossible:
55.6%; p = 0.01). During medical interventions, 5.6% [1/18] of the PNB-patients
and 58.3% [7/12] of the AS-patients experienced pain (p<0.01). Recorded pain
scores were significantly lower in the PNB-group during prehospital medical
intervention (median[IQR] NRS PNB: 0[0-0]) compared to the AS-group (6[0-8];
p<0.001) as well as on first day post presentation (NRS PNB: 1[0-5], AS: 5[5-7];
p = 0.050). All patients of the PNB-group would recommend their analgesic
technique (AS: 50.0%, p<0.01). CONCLUSIONS: Prehospital ultrasound-guided PNB is
rapidly performed in extremity injuries with high success. Compared to the
commonly used AS in trauma patients, PNB significantly reduces pain intensity and
severity.
PMID- 29965992
TI - Non-randomized controlled trial of the long-term efficacy of an Ecohealth
intervention against Chagas disease in Yucatan, Mexico.
AB - Non-domiciliated intrusive triatomine vectors are responsible for a low but
significant transmission of Trypanosoma cruzi to humans. Their control is a
challenge as insecticide spraying is of limited usefulness, and alternative
strategies need to be developed for a sustainable control. We performed a non
randomized controlled trial of an Ecohealth intervention based on window insect
screens and community participation to reduce house infestation by Triatoma
dimidiata in two rural villages in Yucatan, Mexico. Efficacy of the intervention
was measured over a three years follow-up period and entomological indicators
showed that the proportion of triatomines found inside houses was significantly
reduced in houses with insect screens, which effectively kept more bugs on the
outside of houses. Using a previously developed model linking entomological data
to the prevalence of infection in human, we predicted that the intervention would
lead to a 32% reduction in yearly incidence and in the prevalence of T. cruzi
infection. The cost for the coverage of all the windows of a house was of
comparable magnitude to what families currently spend on various domestic
insecticide, and most screens were still in good conditions after three years. In
conclusion, the Ecohealth approach proposed here is effective for the long-term
and sustainable control of intrusive T. dimidiata vectors in the Yucatan
peninsula, Mexico. This strategy may also be easily adapted to other intrusive
triatomine species as well as other regions/countries with comparable eco
epidemiological settings, and would be an excellent component of a larger
integrated program for the control of a variety of other vector-borne diseases,
bringing additional benefits to the communities. Our results should encourage a
further scaling-up of our implementation strategy in additional villages in the
region.
PMID- 29965993
TI - SYNTAX score II predicts long-term mortality in patients with one- or two-vessel
disease.
AB - OBJECTIVE: SYNTAX score II (SSII) is a long-term mortality prediction model to
guide the decision making of the heart-team between coronary artery bypass
grafting or percutaneous coronary intervention (PCI) in patients with left main
or three-vessel coronary artery disease. This study aims to investigate the long
term predictive value of SSII for all-cause mortality in patients with one- or
two-vessel disease undergoing PCI. METHODS: A total of 628 patients (76% men,
mean age: 61+/-10 years) undergoing PCI due to stable angina pectoris (43%) or
acute coronary syndrome (57%), included between January 2008 and June 2013, were
eligible for the current study. SSII was calculated using the original SYNTAX
score website (www.syntaxscore.com). Cox regression analysis was used to assess
the association between continuous SSII and long-term all-cause mortality. The
area under the receiver-operating characteristic curve was used to assess the
performance of SSII. RESULTS: SSII ranged from 6.6 to 58.2 (median: 20.4,
interquartile range: 16.1-26.8). In multivariable analysis, SSII proved to be an
independent significant predictor for 4.5-year mortality (hazard ratio per point
increase: 1.10; 95% confidence interval: 1.07-1.13; p<0.001). In terms of
discrimination, SSII had a concordance index of 0.77. CONCLUSION: In addition to
its established value in patients with left main and three-vessel disease, SSII
may also predict long-term mortality in PCI-treated patients with one- or two
vessel disease.
PMID- 29965994
TI - A retrospective evaluation of bites at risk of rabies transmission across 7
years: The need to improve surveillance and reporting systems for rabies
elimination.
AB - The vast majority of rabies deaths occur in developing countries and rural areas.
Due to the absence of surveillance and the lack of reliable information, many
endemic countries are not able to assess their rabies burden and implement
appropriate solutions. This study reports the incidence of animal bites
considered at risk of rabies transmission, along with rates and determinants of
the adherence to post-exposure prophylaxis (PEP) between 2008 and 2014 in Dodoma
Region, Tanzania. A retrospective analysis of rabid animal bites considered at
risk of rabies transmission at Dodoma Regional Referral Hospital (DRRH) during
2008-2014 was conducted. Data were collected from the registers of patients
presenting to the hospital because of a potential rabies exposure. The patients
were assessed by a trained health worker and each bite was considered as "at risk
of rabies" based on the victim's description of the event. Overall, 10,771
patients coming from Dodoma Region attended DRRH because of a bite from a
suspected rabid animal, giving a mean incidence of 74 bites at risk of rabies
transmission per 100,000 persons per year. Overall, only 46.0% of people exposed
received a complete course of PEP and 61.6% attended the clinic within 48 hours
after the bite. Multivariate analysis shows that people age >15 years, residence
in rural areas and occurrence during the rainy season were independently
associated to delayed access to care. Male gender, age below 15 years. and bites
occurring during the dry season were associated with completion of PEP. In this
area with a high rate of at-risk bites, several factors-mainly related to health
care access and to the affordability and delivery of rabies vaccines-still need
to be addressed in order to reduce gender and social inequalities in rabies
prevention and control. Further efforts are required to establish an efficient
rabies surveillance system in Dodoma Region.
PMID- 29965995
TI - A system-based analysis of the genetic determinism of udder conformation and
health phenotypes across three French dairy cattle breeds.
AB - Using GWAS to identify candidate genes associated with cattle morphology traits
at a functional level is challenging. The main difficulty of identifying
candidate genes and gene interactions associated with such complex traits is the
long-range linkage disequilibrium (LD) phenomenon reported widely in dairy
cattle. Systems biology approaches, such as combining the Association Weight
Matrix (AWM) with a Partial Correlation in an Information Theory (PCIT)
algorithm, can assist in overcoming this LD. Used in a multi-breed and multi
phenotype context, the AWM-PCIT could aid in identifying udder traits candidate
genes and gene networks with regulatory and functional significance. This study
aims to use the AWM-PCIT algorithm as a post-GWAS analysis tool with the goal of
identifying candidate genes underlying udder morphology. We used data from 78,440
dairy cows from three breeds and with own phenotypes for five udder morphology
traits, five production traits, somatic cell score and clinical mastitis. Cows
were genotyped with medium (50k) or low-density (7 to 10k) chips and imputed to
50k. We performed a within breed and trait GWAS. The GWAS showed 9,830
significant SNP across the genome (p < 0.05). Five thousand and ten SNP did not
map a gene, and 4,820 SNP were within 10-kb of a gene. After accounting for
1SNP:1gene, 3,651 SNP were within 10-kb of a gene (set1), and 2,673 significant
SNP were further than 10-kb of a gene (set2). The two SNP sets formed 6,324 SNP
matrix, which was fitted in an AWM-PCIT considering udder depth/ development as
the key trait resulting in 1,013 genes associated with udder morphology, mastitis
and production phenotypes. The AWM-PCIT detected ten potential candidate genes
for udder related traits: ESR1, FGF2, FGFR2, GLI2, IQGAP3, PGR, PRLR, RREB1,
BTRC, and TGFBR2.
PMID- 29965996
TI - Molecular Imaging of endometrial sentinel lymph nodes utilizing fluorescent
labeled Tilmanocept during robotic-assisted surgery in a porcine model.
AB - Molecular imaging with a fluorescent version of Tilmanocept may permit an
accurate and facile detection of sentinel nodes of endometrial cancer.
Tilmanocept accumulates in sentinel lymph nodes (SLN) by binding to a cell
surface receptor unique to macrophages and dendritic cells. Four female Yorkshire
pigs underwent cervical stromal injection of IRDye800-Tilmanocept, a molecular
imaging agent tagged with near-infrared fluorescent dye and radiolabeled with
gallium-68 and technetium-99m. PET/CT scans 1.5 hours post-injection provided pre
operative SLN mapping. Robotic-assisted lymphadenectomy was performed two days
after injection, using the FireFly imaging system to identify nodes demonstrating
fluorescent signal. After removal of fluorescent nodes, pelvic and periaortic
node dissections were performed. Nodes were assayed for technetium-99m activity,
and SLNs were established using the "10%-rule", requiring that the radioactivity
of additional SLNs be greater than 10% of the "hottest" SLN. Thirty-four nodal
samples were assayed ex vivo for radioactivity. All the SLNs satisfying the "10%
rule" were detected using the FireFly system. Five fluorescent nodes were
detected, corresponding with preoperative PET/CT scan. Three pigs had one SLN and
one pig had two SLNs, with 100% concordance between fluorescence and
radioactivity. Fluorescent-labeled Tilmanocept permits real-time intraoperative
detection of SLNs during robotic-assisted lymphadenectomy for endometrial cancer
in a porcine model. When radiolabeled with gallium-68, Tilmanocept allows for
preoperative localization of SLNs using PET/CT, and shows specificity to SLNs
with persistent fluorescent signal, detectable using the FireFly system, for two
days post-injection. In conclusion, these findings suggest that a phase I trial
in human subjects is warranted, and that a long-term goal of an intra-operative
administration of non-radioactive fluorescent-labeled Tilmanocept is possible.
PMID- 29965998
TI - Habitual physical activity levels do not predict leg strength and power in
healthy, active older adults.
AB - Physical activity is considered crucial in attenuating losses in strength and
power associated with ageing. However, in well-functioning, active older adults
the relationship between habitual physical activity and muscle function is
surprisingly unclear. Leg press velocity, force, and power, were compared between
50 older and 30 younger healthy individuals, and associations with habitual
physical activity explored. An incremental power test was performed on a
pneumatic leg press, with theoretical maximum velocity, force, and power
calculated. Vastus lateralis muscle thickness was measured by ultrasound, and
participants wore a combined accelerometer and heart rate monitor for 6-days of
free-living. Older individuals produced lower absolute maximum velocity, force,
and power, than younger individuals. When accounting for smaller muscle size,
older individual's maximum force and power remained markedly lower. Both groups
were active, however using age specific thresholds for classifying physical
activity, the older individuals engaged in twice the amount of moderate-to
vigorous physical activity in comparison to the younger individuals. There were
no associations between any characteristics of muscle function and physical
activity. These data support that the ability to generate force and power
deteriorates with age, however habitual physical activity levels do not explain
inter-individual differences in muscle function in active older individuals.
PMID- 29965997
TI - Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a
treatment for breast cancer.
AB - Most breast cancer deaths are caused by metastasis and treatment options beyond
radiation and cytotoxic drugs, which have severe side effects, and hormonal
treatments, which are or become ineffective for many patients, are urgently
needed. This study reanalyzed existing data from three genome-wide association
studies (GWAS) using a novel computational biostatistics approach (muGWAS), which
had been validated in studies of 600-2000 subjects in epilepsy and autism. MuGWAS
jointly analyzes several neighboring single nucleotide polymorphisms while
incorporating knowledge about genetics of heritable diseases into the statistical
method and about GWAS into the rules for determining adaptive genome-wide
significance. Results from three independent GWAS of 1000-2000 subjects each,
which were made available under the National Institute of Health's "Up For A
Challenge" (U4C) project, not only confirmed cell-cycle control and receptor/AKT
signaling, but, for the first time in breast cancer GWAS, also consistently
identified many genes involved in endo-/exocytosis (EEC), most of which had
already been observed in functional and expression studies of breast cancer. In
particular, the findings include genes that translocate (ATP8A1, ATP8B1, ANO4,
ABCA1) and metabolize (AGPAT3, AGPAT4, DGKQ, LPPR1) phospholipids entering the
phosphatidylinositol cycle, which controls EEC. These novel findings suggest
scavenging phospholipids as a novel intervention to control local spread of
cancer, packaging of exosomes (which prepare distant microenvironment for organ
specific metastases), and endocytosis of beta1 integrins (which are required for
spread of metastatic phenotype and mesenchymal migration of tumor cells). Beta
cyclodextrins (betaCD) have already been shown to be effective in in vitro and
animal studies of breast cancer, but exhibits cholesterol-related ototoxicity.
The smaller alpha-cyclodextrins (alphaCD) also scavenges phospholipids, but
cannot fit cholesterol. An in-vitro study presented here confirms hydroxypropyl
(HP)-alphaCD to be twice as effective as HPbetaCD against migration of human
cells of both receptor negative and estrogen-receptor positive breast cancer. If
the previous successful animal studies with betaCDs are replicated with the safer
and more effective alphaCDs, clinical trials of adjuvant treatment with alphaCDs
are warranted. Ultimately, all breast cancer are expected to benefit from
treatment with HPalphaCD, but women with triple-negative breast cancer (TNBC)
will benefit most, because they have fewer treatment options and their cancer
advances more aggressively.
PMID- 29965999
TI - Increased body fat percentage in patients with hepatitis B and C virus infection.
AB - Accumulated evidence has suggested associations between glucose abnormalities and
insulin resistance with hepatitis C virus (HCV) and hepatitis B virus (HBV)
infections. However, few studies have reported the effect of hepatitis virus
infections on body composition. Our aim was to explore the association of
hepatitis virus infections with percent body fat (PBF) in a cross-sectional
analysis. A total of 69226 subjects obtained from the health examinations at Tri
Service General Hospital (TSGH) from 2010 to 2016 were enrolled in the study.
Participants were divided into subgroups based on the presence of hepatitis B
surface antigen (HBsAg) and anti-HCV. PBF was measured by bioelectrical impedance
analysis (BIA). A multivariable linear regression model was applied to test the
association of hepatitis virus infections with PBF and glycemic status. In male
participants, hepatitis virus infections were closely associated with increased
PBF, especially in those subjects with HCV/HBV coinfection. HCV/HBV coinfection
was positively correlated with fasting plasma glucose and postprandial glucose
while HCV and HBV mono-infection were not. The impact of hepatitis virus
infection on increased PBF was observed in general population with gender
difference. A further study on the treatment of hepatitis virus infection might
help prevent the development of obesity-related diseases.
PMID- 29966000
TI - Correction: Low Carbohydrate versus Isoenergetic Balanced Diets for Reducing
Weight and Cardiovascular Risk: A Systematic Review and Meta-Analysis.
AB - [This corrects the article DOI: 10.1371/journal.pone.0100652.].
PMID- 29966001
TI - The stress response gene ATF3 is a direct target of the Wnt/beta-catenin pathway
and inhibits the invasion and migration of HCT116 human colorectal cancer cells.
AB - Aberrant Wnt/beta-catenin signaling is implicated in tumorigenesis and the
progression of human colorectal cancers, and mutations in the components of the
Wnt/beta-catenin signaling pathway are observed in the majority of patients.
Therefore, extensive studies on the Wnt signaling pathway and its target genes
are crucial to understand the molecular events of tumorigenesis and develop an
efficacious therapy. In this study, we showed that the stress response gene ATF3
is transcriptionally activated by the binding of beta-catenin and TCF4 to the
redundant TCF4 site at the proximal promoter region of the ATF3 gene, indicating
that ATF3 is a direct target of the Wnt/beta-catenin pathway. The loss of
function or overexpression studies showed that ATF3 inhibited the migration or
invasion of HCT116 cells. The expression of some MMP and TIMP genes and the ratio
of MMP2/9 to TIMP3/4 mRNAs was differentially regulated by ATF3. Therefore,
though ATF3 is activated downstream of the Wnt/beta-catenin pathway, it acts as a
negative regulator of the migration and invasion of HCT116 human colon cancer
cells exhibiting aberrant Wnt/beta-catenin activity. ATF3 is a candidate
biomarker and target for human colorectal cancer treatment and prevention.
PMID- 29966002
TI - Old principles, persisting challenges: Maternal health care market alignment in
Mexico in the search for UHC.
AB - The purpose of this study is to analyze the alignment of supply and demand for
antenatal care (ANC) in Mexico based on the definition of access provided by
Donabedian: the "degree of adjustment" between resources and needs. Alignment was
studied in the teenage and adult population of Mexico that lacked conventional
social security between 2008 and 2015, a period of expanding financial resources
for health and public health insurance coverage. Spatial econometric methods were
used to analyze data from the Ministry of Health on the supply and demand for ANC
in 2,314 municipalities (94% of all municipalities in Mexico). During this
period, the relative weight of ANC demand among adolescents increased 37% while
the production of antenatal consultations for adolescent and adult women remained
unchanged. Bivariate spatial analyses of correlation between supply and demand
for ANC services yielded a minimal spatial correlation, or lack of territorial
correspondence, between supply and demand among women in both age groups. Spatial
econometric analysis confirmed a non-significant association between supply and
demand for ANC services. Our findings suggest the existence of misalignment
between supply and demand for these services. This requires a reassessment of the
management and delivery of ANC services at the local level in order to increase
effective coverage and improve the overall performance of the health system.
PMID- 29966003
TI - Whole genome comparison of Aspergillus flavus L-morphotype strain NRRL 3357
(type) and S-morphotype strain AF70.
AB - Aspergillus flavus is a saprophytic fungus that infects corn, peanuts, tree nuts
and other agriculturally important crops. Once the crop is infected the fungus
has the potential to secrete one or more mycotoxins, the most carcinogenic of
which is aflatoxin. Aflatoxin contaminated crops are deemed unfit for human or
animal consumption, which results in both food and economic losses. Within A.
flavus, two morphotypes exist: the S strains (small sclerotia) and L strains
(large sclerotia). Significant morphological and physiological differences exist
between the two morphotypes. For example, the S-morphotypes produces sclerotia
that are smaller (< 400 MUm), greater in quantity, and contain higher
concentrations of aflatoxin than the L-morphotypes (>400 MUm). The morphotypes
also differ in pigmentation, pH homeostasis in culture and the number of spores
produced. Here we report the first full genome sequence of an A. flavus S
morphotype, strain AF70. We provide a comprehensive comparison of the A. flavus S
morphotype genome sequence with a previously sequenced genome of an L-morphotype
strain (NRRL 3357), including an in-depth analysis of secondary metabolic
clusters and the identification SNPs within their aflatoxin gene clusters.
PMID- 29966004
TI - Evaluation of glycoprotein Ov8 as a potential antigen for an OvHV-2-specific
diagnostic assay.
AB - Gammaherpesviruses in the genus Macavirus establish clinically unapparent
persistent infections in reservoir species. Transmission of some of these
viruses, including alcelaphine herpesvirus 1 (AlHV-1) and ovine herpesvirus 2
(OvHV-2), to clinically susceptible species in the order Artiodactyla can result
in malignant catarrhal fever (MCF), a usually fatal lymphoproliferative disease.
Serology can be used to identify MCF virus (MCFV)-infected carrier animals.
However, all current serological assays utilize AlHV-1 antigens, thus none is
specific for OvHV-2. In situations where sheep and other MCFV carriers are
present, such as in zoos and game farms, an OvHV-2-specific assay would determine
if OvHV-2 is present in the population. In this study, a recombinant protein
containing a truncated OvHV-2 Ov8 glycoprotein was expressed and evaluated as a
suitable target antigen to specifically detect OvHV-2 infection using an enzyme
linked immunosorbent assay (ELISA). A competitive inhibition (CI)-ELISA that
detects an epitope conserved among all MCFVs was used to categorize, as positive
or negative, sera from 205 domestic sheep. The Ov8 assay showed 100% diagnostic
sensitivity, 98.97% diagnostic specificity, 99.07% positive predictive value, and
100% negative predictive value and very high agreement (kappa = 0.990 and 95% CI
= 0.971-1.000) with the CI-ELISA. Sera from animals infected with MCFVs other
than OvHV-2 did not cross-react with Ov8 (100% negative predictive value). These
data support the use of the Ov8 ELISA as an OvHV-2-specific diagnostic assay.
PMID- 29966006
TI - Preparation and characterization of functionalized heparin-loaded poly-E
caprolactone fibrous mats to prevent infection with human papillomaviruses.
AB - In this study, heparin-loaded poly-E-caprolactone (PCL) fibrous mats were
prepared and characterized based on their physical, cytotoxic, thermal, and
biological properties. The main objective of the work described here was to test
the hypothesis that incorporation of heparin into a PCL carrier could serve as
bio-compatible material capable of inhibiting Human Papillomavirus (HPV)
infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a
slow heparin release to inhibit a virus in solution was tested. Thus, one
material was produced via conventional heparin matrix encapsulation and
electrohydrodynamic fiber processing in one step. A second type of material was
obtained via heparin crosslinking. This was achieved by running a carbodiimide/N
hydroxysuccinimide (EDC/NHS) coupling reaction on preformed PCL fibers. In vitro
HPV16 L1 protein binding capacity studies were performed. Infectivity assays were
done using HPV16 pseudoviruses (PsVs) carrying a GFP plasmid to directly test the
ability of the fibrous mats to prevent internalization of HPV PsVs. The
crosslinked heparin material presented a dissociation constant (Kd) value
comparable to those found in the literature for different heparin-protein L1
peptide interactions. Both materials significantly reduced internalization of HPV
PsVs, with a reduction of 94% of PsVs internalization when matrix encapsulated
heparin-loaded material was present. Differences in performance between the two
proposed structures are discussed.
PMID- 29966005
TI - Dissecting conformational changes in APP's transmembrane domain linked to epsilon
efficiency in familial Alzheimer's disease.
AB - The mechanism by which familial Alzheimer's disease (FAD) mutations within the
transmembrane domain (TMD) of the Amyloid Precursor Protein (APP) affect epsilon
endoproteolysis is only poorly understood. Thereby, mutations in the cleavage
domain reduce epsilon-efficiency of gamma-secretase cleavage and some even shift
entry into production lines. Since cleavage occurs within the TMD, a relationship
between processing and TMD structure and dynamics seems obvious. Using molecular
dynamic simulations, we dissect the dynamic features of wild-type and seven FAD
mutants into local and global components. Mutations consistently enhance hydrogen
bond fluctuations upstream of the epsilon-cleavage sites but maintain strong
helicity there. Dynamic perturbation-response scanning reveals that FAD-mutants
target backbone motions utilized in the bound state. Those motions, obscured by
large-scale motions in the pre-bound state, provide (i) a dynamic mechanism
underlying the proposed coupling between binding and epsilon-cleavage, (ii) key
sites consistent with experimentally determined docking sites, and (iii) the
distinction between mutants and wild-type.
PMID- 29966008
TI - Subjective speech quality measurement with and without parallel task: Laboratory
test results comparison.
AB - This paper focuses on a novel methodology of subjective speech quality
measurement and repeatability of its results between laboratory conditions and
simulated environmental conditions. A single set of speech samples was distorted
by various background noises and low bit-rate coding techniques. This study aimed
to compare results of subjective speech quality tests with and without a parallel
task deploying the ITU-T P.835 methodology. Afterward, tests results performed
with and without a parallel task were compared using Pearson correlation, CI95,
and numbers of opposite pair-wise comparisons. The tests show differences in
results in the case of a parallel task.
PMID- 29966007
TI - Anticancer potential, molecular mechanisms and toxicity of Euterpe oleracea
extract (acai): A systematic review.
AB - Cancer is an increasingly frequent malignancy worldwide, and despite the advances
in drug development, it is still necessary to develop new plant-derived
medicines. Euterpe oleracea (acai) is abundant in South and Central America and
has health benefits due to its high levels of phytochemicals, including lignans
and polyphenols. The aim of this review was to systematically describe the safety
and antitumor effects of acai in preclinical models using rodents to provide a
more comprehensive assessment of acai for both therapeutic uses and the
development of future clinical studies in cancer. Eligible studies were
identified using four international databases (PubMed, Medline, Lilacs and
SciELO) from their inception date through December 2017. The included studies
were analyzed with methodological rigor (QATRS) to enable better quality control
for these experimental studies. Sixty publications were identified in the
databases, but only 9 articles were eligible: 6 evaluated the pharmacological
effects of acai in animal models of cancer (1 model each of esophageal cancer,
urothelial cancer, melanoma and Walker-256 tumor and 2 models of colon cancer),
and 3 were toxicological assays using preclinical models with rodents. Overall,
747 animals were analyzed. On a QATRS score scale of 0-20, the quality of the
studies ranged from 16 to 20 points. Pulp was the main fraction of acai
administered, and an oral administration route was most common. The acai dosage
administered by gavage ranged from 30 mg/kg to 40,000 mg/kg, and acai fed in the
diet accounted for 2.5% to 5% of the diet. The anticarcinogenic and
chemopreventive activities of acai were observed in all experimental models of
cancer and reduced the incidence, tumor cell proliferation, multiplicity and size
of the tumors due to the antiinflammatory, antiproliferative and proapoptotic
properties of acai. No genotoxic effects were observed after acai administration.
The results of this review suggest that acai is safe and can be used as a
chemoprotective agent against cancer development. Acai therapy may be a novel
strategy for treating cancer.
PMID- 29966009
TI - Gene expression in the corneal endothelium of Fuchs endothelial corneal dystrophy
patients with and without expansion of a trinucleotide repeat in TCF4.
AB - Fuchs Endothelial Corneal Dystrophy (FECD) is a late onset, autosomal dominant
eye disease that can lead to loss of vision. Expansion of a CTG trinucleotide
repeat in the third intron of the transcription factor 4 (TCF4) gene is highly
associated with FECD. However, only about 75% of FECD patients in the northern
European population possess an expansion of this repeat. The remaining FECD cases
appear to be associated with variants in other genes. To better understand the
pathophysiology of this disease, we compared gene expression profiles of corneal
endothelium from FECD patients with an expanded trinucleotide repeat (RE+) to
those that do not have a repeat expansion (RE-). Comparative analysis of these
two cohorts showed widespread RNA mis-splicing in RE+, but not in RE- samples.
Quantitatively, we identified 39 genes in which expression was significantly
different between RE+ and RE- samples. Examination of the mutation profiles in
the RE- samples did not find any mutations in genes previously associated with
FECD, but did reveal one sample with a rare variant of laminin subunit gamma 1
(LAMC1) and three samples with rare variants in the gene coding for the
mitochondrial protein peripheral-type benzodiazepine receptor-associated protein
1 (TSPOAP1).
PMID- 29966010
TI - Correction: Evaluation of a community-based intervention to improve maternal and
neonatal health service coverage in the most rural and remote districts of
Zambia.
AB - [This corrects the article DOI: 10.1371/journal.pone.0190145.].
PMID- 29966011
TI - 18F-FDG PET intensity correlates with a hypoxic gene signature and other
oncogenic abnormalities in operable non-small cell lung cancer.
AB - BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is
critical for staging non-small-cell lung cancer (NSCLC). While PET intensity
carries prognostic significance, the genetic abnormalities associated with
increased intensity remain unspecified. METHODS: NSCLC samples (N = 34) from 1999
to 2011 for which PET data were available were identified from a prospectively
collected tumor bank. PET intensity was classified as mild, moderate, or intense
based on SUVmax measurement or radiology report. Associations between genome-wide
expression (RNAseq) and PET intensity were determined. Associations with overall
survival were then validated in two external NSCLC cohorts. RESULTS: Overall
survival was significantly worse in patients with PET-intense (N = 11) versus
mild (N = 10) tumors (p = 0.039). Glycolytic gene expression patterns were
markedly similar between intense and mild tumors. Gene ontology analysis
demonstrated significant enhancement of cell-cycle and proliferative processes in
FDG-intense tumors (p<0.001). Gene set enrichment analysis (GSEA) suggested
associations between PET-intensity and canonical oncogenic signaling pathways
including MYC, NF-kappaB, and HIF-1. Using an external cohort of 25 tumors with
PET and genomic profiling data, common genes and gene sets were validated for
additional study (P<0.05). Of these common gene sets, 20% were associated with
hypoxia or HIF-1 signaling. While HIF-1 expression did not correlate with poor
survival in the NSCLC validation cohort (N = 442), established targets of hypoxia
signaling (PLAUR, ADM, CA9) were significantly associated with poor overall
survival. CONCLUSIONS: PET-intensity is associated with a variety of oncogenic
alterations in operable NSCLC. Adjuvant targeting of these pathways may improve
survival among patients with PET-intense tumors.
PMID- 29966012
TI - Impact of clinical severity of stroke on the severity and recovery of
visuospatial neglect.
AB - BACKGROUND AND PURPOSE: There is growing evidence that visuospatial neglect (VSN)
is associated with lower functional performance in other modalities and is not
restricted to the lesioned hemisphere alone, and may also affect the non-lesioned
hemisphere in severe first-ever strokes. We aimed to investigate the longitudinal
association between the severity of VSN, as reflected by the extent of
ipsilesional and contralesional spatial attention deficit, and clinical severity
of stroke. METHODS: This is a secondary data analysis with merged data from two
prospective cohort studies. Resulting in 90 patients and 8 longitudinal
measurements at 1, 2, 3, 4, 5, 8, 12, and 26 weeks post-stroke onset. A letter
cancellation test (LCT) was used as the primary outcome measure to demonstrate
presence and severity of VSN. The clinical severity of stroke was classified
using the Bamford Classification. RESULTS: No significant association between
clinical severity and the number of ipsilesional, as well as contralesional,
omissions on the LCT was observed. Recovery of VSN at the contralesional
hemiplegic, as well as ipsilesional non-hemiplegic side, was only dependent on
'time' as a reflection of spontaneous neurobiological recovery post-stroke. The
recovery of the ipsilesional extension of VSN was significantly slower for the
total anterior circulation infarct (TACI) group compared to the non-TACI group.
CONCLUSIONS: Larger strokes have a significant negative impact on recovery of
visual attention at the non-hemiplegic side. No clinical determinants that
regulate spontaneous time-dependent recovery of VSN were found. While early
'stroke severity' has been regarded as a strong predictor of functional outcome
at a group level, other prognostic factors (demographic, stroke related) need to
be determined. CLINICAL TRIAL REGISTRATION: EXPLICIT-stroke Trial:
http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1424 Stroke Intensity
Trial: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1665.
PMID- 29966013
TI - Improving quality and safety of care in nursing homes by team support for
strengths use: A survey study.
AB - Growing evidence suggests that workload has an adverse effect on quality of care
and patient safety in nursing homes. A novel job resource that may improve
quality of care and patient safety and alleviate the negative effect of workload
in nursing homes is team support for strengths use. This refers to team members'
beliefs concerning the extent to which the team they work in actively supports
them in applying their individual strengths at work. The objective was to
investigate the relationships between workload, team support for strengths use,
quality of care, and patient safety in nursing homes. We collected (cross
sectional) survey data from 497 caregivers from 74 teams in seven different
nursing homes. The survey included measures on perceived workload, team support
for strengths use, caregivers' perception of the quality of care provided by the
team and four safety incidents (i.e. fall incidents, medication errors, pressure
ulcers, incidents of aggression). After controlling for age, team size, team
tenure, organizational tenure, and nursing home, multilevel regression analyses
(i.e. individual and team level) showed that perceived workload was not
significantly related to perceived team-based quality of care and the frequency
of safety incidents. Team support for strengths use was positively related to
perceived team-based quality of care, negatively related to medication errors,
but not significantly related to fall incidents, pressure ulcers, and aggression
incidents. Finally, we found that perceived workload had a negative effect on
perceived team-based quality of care when team support for strengths use is low
and no significant effect on perceived team-based quality of care when team
support for strengths use is high. This study provides promising evidence for a
novel avenue for promoting team-based quality of care in nursing homes.
PMID- 29966014
TI - Urothelial bladder cancer may suppress perforin expression in CD8+ T cells by an
ICAM-1/TGFbeta2 mediated pathway.
AB - The immune system plays a significant role in urothelial bladder cancer (UBC)
progression, with CD8+ T cells being capable to directly kill tumor cells using
perforin and granzymes. However, tumors avoid immune recognition by escape
mechanisms. In this study, we aim to demonstrate tumor immune escape mechanisms
that suppress CD8+ T cells cytotoxicity. 42 patients diagnosed with UBC were
recruited. CD8+ T cells from peripheral blood (PB), sentinel nodes (SN), and
tumor were analyzed in steady state and in vitro-stimulated conditions by flow
cytometry, RT-qPCR, and ELISA. Mass spectrometry (MS) was used for identification
of proteins from UBC cell line culture supernatants. Perforin was surprisingly
found to be low in CD8+ T cells from SN, marked by 1.8-fold decrease of PRF1
expression, with maintained expression of granzyme B. The majority of perforin
deficient CD8+ T cells are effector memory T (TEM) cells with exhausted Tc2 cell
phenotype, judged by the presence of PD-1 and GATA-3. Consequently, perforin
deficient CD8+ T cells from SN are low in T-bet expression. Supernatant from
muscle invasive UBC induces perforin deficiency, a mechanism identified by MS
where ICAM-1 and TGFbeta2 signaling were causatively validated to decrease
perforin expression in vitro. Thus, we demonstrate a novel tumor escape
suppressing perforin expression in CD8+ T cells mediated by ICAM-1 and TGFbeta2,
which can be targeted in combination for cancer immunotherapy.
PMID- 29966016
TI - Sustained-release lidocaine sheet for pain following tooth extraction: A
randomized, single-blind, dose-response, controlled, clinical study of efficacy
and safety.
AB - BACKGROUND: We have synthesized a sustained-release lidocaine sheet (SRLS) using
biodegradable polymers and previously demonstrated its safety and long-term
analgesic effect in the normal mucous membrane of healthy human volunteers.
OBJECTIVES: The aim of this clinical study was to evaluate the efficacy, safety,
and appropriate dose of the SRLS for pain following tooth extraction. DESIGN:
Randomized, single-blind, dose-response, controlled, clinical study (Phase 1/2).
METHODS: The patients in this trial were enrolled between January 2014 and
December 2016. A total of 99 patients were randomly divided into 5 groups as
follows: the Non-administration group received the conventional extraction; the
Poly Lactic-co-Glycolic Acid (PLGA) 100 mg control group received the PLGA matrix
without lidocaine; the SRLS 100 mg group received a single sheet of SRLS 100 mg;
the SRLS 200 mg group received double sheets of SRLS 100 mg; and the SRLS 400 mg
administration group received four sheets of SRLS 100 mg. A study drug was
inserted into the defect socket after the extraction, and postoperative pain
intensity, satisfaction with postoperative pain relief, adverse events, and
postoperative supplemental analgesic rescue use (time, dose) were investigated by
patient self-report. RESULTS: In total, 94 (94.9%) patients completed the study.
There were no significant differences in postoperative pain intensity,
satisfaction with postoperative pain relief, and postoperative supplemental
analgesic rescue use among the 5 groups. There were no serious side effects,
including a plasma concentration increase of lidocaine, attributable to the SRLS.
CONCLUSIONS: Administration of the SRLS at 100 mg may have clinical therapeutic
potential for pain relief following tooth extraction. The safety of the SRLS for
patients undergoing tooth extraction was demonstrated. TRIAL REGISTRATION: The
University Hospital Medical Information Network UMIN000011945.
PMID- 29966015
TI - Computational analyses of obesity associated loci generated by genome-wide
association studies.
AB - OBJECTIVES: Genome-wide association studies (GWASs) have discovered associations
of numerous SNPs and genes with obesity. However, the underlying molecular
mechanisms through which these SNPs and genes affect the predisposition to
obesity remain not fully understood. Aims of our study are to comprehensively
characterize obesity GWAS SNPs and genes through computational approaches.
METHODS: For obesity GWAS identified SNPs, functional annotation, effects on
miRNAs binding and impact on protein phosphorylation were performed via
RegulomeDB and 3DSNP, miRNASNP, and the PhosSNP 1.0 database, respectively. For
obesity associated genes, protein-protein interaction network construction, gene
ontology and pathway enrichment analyses were performed by STRING, PANTHER and
STRING, respectively. RESULTS: A total of 445 SNPs are significantly associated
with obesity related phenotypes at threshold P < 5*10-8. A number of SNPs were
eQTLs for obesity associated genes, some SNPs located at binding sites of obesity
related transcription factors. SNPs that might affect miRNAs binding and protein
phosphorylation were identified. Protein-protein interaction network analysis
identified the highly-interconnected "hub" genes. Obesity associated genes mainly
involved in metabolic process and catalytic activity, and significantly enriched
in 15 signal pathways. CONCLUSIONS: Our results provided the targets for follow
up experimental testing and further shed new light on obesity pathophysiology.
PMID- 29966017
TI - A simple magnetoencephalographic auditory paradigm may aid in confirming left
hemispheric language dominance in epilepsy patients.
AB - OBJECTIVE: The intracarotid amobarbital procedure (IAP) is the current "gold
standard" in the preoperative assessment of language lateralization in epilepsy
surgery candidates. It is, however, invasive and has several limitations. Here we
tested a simple noninvasive language lateralization test performed with
magnetoencephalography (MEG). METHODS: We recorded auditory MEG responses to
pairs of vowels and pure tones in 16 epilepsy surgery candidates who had
undergone IAP. For each individual, we selected the pair of planar gradiometer
sensors with the strongest N100m response to vowels in each hemisphere and-from
the vector sum of signals of this gradiometer pair-calculated the vowel/tone
amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the
laterality index: LI = (L-R)/(L+R). In addition to the analysis using a single
sensor pair, an alternative analysis was performed using averaged responses over
18 temporal sensor pairs in both hemispheres. RESULTS: The laterality index did
not correlate significantly with the lateralization data obtained from the IAP.
However, an MEG pattern of stronger responses to vowels than tones in the left
hemisphere and stronger responses to tones than vowels in the right hemisphere
was associated with left-hemispheric language dominance in the IAP in all the six
patients who showed this pattern. This results in a specificity of 100% and a
sensitivity of 67% of this MEG pattern in predicting left-hemispheric language
dominance (p = 0.01, Fisher's exact test). In the analysis using averaged
responses over temporal channels, one additional patient who was left-dominant in
IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p =
0.003). SIGNIFICANCE: This simple MEG paradigm shows promise in feasibly and
noninvasively confirming left-hemispheric language dominance in epilepsy surgery
candidates. It may aid in reducing the need for the IAP, if the results are
confirmed in larger patient samples.
PMID- 29966018
TI - Analysis of factors affecting the variability of a quantitative suspension bead
array assay measuring IgG to multiple Plasmodium antigens.
AB - Reducing variability of quantitative suspension array assays is key for multi
center and large sero-epidemiological studies. To maximize precision and
robustness of an in-house IgG multiplex assay, we analyzed the effect of several
conditions on variability to find the best combination. The following assay
conditions were studied through a fractional factorial design: antigen-bead
coupling (stock vs. several), sample predilution (stock vs. daily), temperature
of incubation of sample with antigen-bead (22 degrees C vs. 37 degrees C), plate
washing (manual vs. automatic) and operator expertise (expert vs. apprentice).
IgG levels against seven P. falciparum antigens with heterogeneous
immunogenicities were measured in test samples, in a positive control and in
blanks. We assessed the variability and MFI quantification range associated to
each combination of conditions, and their interactions, and evaluated the minimum
number of samples and blank replicates to achieve good replicability. Results
showed that antigen immunogenicity and sample seroreactivity defined the optimal
dilution to assess the effect of assay conditions on variability. We found that a
unique antigen-bead coupling, samples prediluted daily, incubation at 22 degrees
C, and automatic washing, had lower variability. However, variability increased
when performing several couplings and incubating at 22 degrees C vs. 37 degrees
C. In addition, no effect of temperature was seen with a unique coupling. The
expertise of the operator had no effect on assay variability but reduced the MFI
quantification range. Finally, differences between sample replicates were
minimal, and two blanks were sufficient to capture assay variability, as
suggested by the constant Intraclass Correlation Coefficient of three and two
blanks. To conclude, a single coupling was the variable that most consistently
reduced assay variability, being clearly advisable. In addition, we suggest
having more sample dilutions instead of replicates to increase the likelihood of
sample MFIs falling in the linear part of the antigen-specific curve, thus
increasing precision.
PMID- 29966019
TI - Serum uric acid and arterial hypertension-Data from Sephar III survey.
AB - OBJECTIVES: This paper aims to evaluate the association between serum uric acid
(SUA) levels, arterial hypertension (HT) prevalence, blood pressure values
control, kidney function and intima media thickness (IMT), as a surrogate marker
of early atherosclerosis, in a representative group of Romanian adult population.
MATERIALS AND METHODS: The study sample consists in 1920 adults included in
SEPHAR III (Study for the Evaluation of Prevalence of Hypertension and
cArdiovascular Risk in Romania) survey (mean age 48.63 years, 52.76% females)
collecting data for SUA levels, blood pressure (BP) measurements, kidney function
by estimated glomerular filtration rate (eGFR) and carotid IMT. SUA levels
between 2,40-5,70mg/dl in females and 3,40-7,00mg/dl in males respectively were
considered normal. HT and HT control were defined according to the current
guidelines. IMT evaluation was assessed by B-mode Doppler ultrasound evaluation.
RESULTS: Hypertensive subjects had significantly higher values of SUA compared
with normotensive subjects, hypertensive patients were 1.713 times more likely to
have higher values of SUA. Among treated hypertensive patients, those without
optimal BP control had significantly higher SUA levels compared with those with
optimal BP control, the presence of hyperuricemia increasing the odds of
suboptimal BP control by 1.023. Hyperuricemic subjects had significantly lower
eGFR values compared with normouricemic ones, on an average with
14.28ml/min/1.73m2 by Modification of Diet in Renal Disease formula (MDRD) and
with 16.64ml/min/1.73m2 by Chronic Kidney Disease Epidemiology Collaboration
formula (CKD-EPI), with an indirect association between SUA levels and eGFR
values (rs = -0.319 / -0.347), independent of age. IMT values recorded in
hyperuricemic subjects were significantly increased, on an average with 0.08mm,
compared with normouricemic subjects, with a direct association between SUA
levels and IMT values (rs = 0.263), independent of BP values. CONCLUSION: The
results of our study offers support that increased SUA levels are associated with
arterial hypertension and with suboptimal BP control in treated hypertensive
subjects. The decline in kidney function, independent of age, and also increased
IMT values as a marker of atherosclerosis, were also correlated with elevated SUA
values. Hyperuricemia screening may have a role in identifying patients at risk
of developing HT and lowering SUA levels may improve not only BP control in
treated HT patients but also decrease total cardiovascular mortality by slowing
the progression of atherosclerosis and renal failure in hypertensive patients.
PMID- 29966020
TI - Nitric oxide alters hyaluronan deposition by airway smooth muscle cells.
AB - Asthma is a chronic inflammatory disease that is known to cause changes in the
extracellular matrix, including changes in hyaluronan (HA) deposition. However,
little is known about the factors that modulate its deposition or the potential
consequences. Asthmatics with high levels of exhaled nitric oxide (NO) are
characterized by greater airway reactivity and greater evidence of airway
inflammation. Based on these data and our previous work we hypothesized that
excessive NO promotes the pathologic production of HA by airway smooth muscle
cells (SMCs). Exposure of cultured SMCs to various NO donors results in the
accumulation of HA in the form of unique, cable-like structures. HA accumulates
rapidly after exposure to NO and can be seen as early as one hour after NO
treatment. The cable-like HA in NO-treated SMC cultures supports the binding of
leukocytes. In addition, NO produced by murine macrophages (RAW cells) and airway
epithelial cells also induces SMCs to produce HA cables when grown in co-culture.
The modulation of HA by NO appears to be independent of soluble guanylate
cyclase. Taken together, NO-induced production of leukocyte-binding HA by SMCs
provides a new potential mechanism for the non-resolving airway inflammation in
asthma and suggests a key role of non-immune cells in driving the chronic
inflammation of the submucosa. Modulation of NO, HA and the consequent immune
cell interactions may serve as potential therapeutic targets in asthma.
PMID- 29966022
TI - The importance of an ecologically valid method in the evaluation of toddler
interaction with coloured liquid laundry detergent capsules.
AB - The colour and appearance of liquid laundry capsules have been implicated in the
risk of attracting the attention of toddlers, and therefore contributing to
poisoning incidents in the home by encouraging interaction. This research set out
to explore if differences in colours and contrasting colour designs used in mono
and multi-coloured capsules result in different levels of attractiveness. This
was performed using two study settings: a laboratory setting (out of context),
and by comparison, a more ecologically valid setting, mimicking the real-world.
Capsule attractiveness to toddlers was measured by visual attention (measured
through eye tracking) and grasping choice (measured as frequency of grasping in a
behavioural task). Results from the research in the out of context setting showed
statistically significant differences in visual attention and grasping choice
between colours and contrasting designs. In the visual attention study a
preference for multi-coloured capsules was shown. In the grasping choice study,
in addition to multi-coloured, mono-coloured white or purple capsules were also
preferred. In the more ecologically valid setting, there were no statistically
significant differences in the visual attention or grasping choice between any of
the capsules. These results were consistent with each other and in line with
market data reflecting poisoning incident rates, which show no change with colour
or contrasting colour design. We suggest that the results from out of context
studies might not be a reliable indicator of real world behaviour. Given the
importance of toddler home safety, using a methodology that is aligned with
market numbers is crucial to develop countermeasures.
PMID- 29966021
TI - The effects of aging on neuropil structure in mouse somatosensory cortex-A 3D
electron microscopy analysis of layer 1.
AB - This study has used dense reconstructions from serial EM images to compare the
neuropil ultrastructure and connectivity of aged and adult mice. The analysis
used models of axons, dendrites, and their synaptic connections, reconstructed
from volumes of neuropil imaged in layer 1 of the somatosensory cortex. This
shows the changes to neuropil structure that accompany a general loss of synapses
in a well-defined brain region. The loss of excitatory synapses was balanced by
an increase in their size such that the total amount of synaptic surface, per
unit length of axon, and per unit volume of neuropil, stayed the same. There was
also a greater reduction of inhibitory synapses than excitatory, particularly
those found on dendritic spines, resulting in an increase in the
excitatory/inhibitory balance. The close correlations, that exist in young and
adult neurons, between spine volume, bouton volume, synaptic size, and docked
vesicle numbers are all preserved during aging. These comparisons display
features that indicate a reduced plasticity of cortical circuits, with fewer,
more transient, connections, but nevertheless an enhancement of the remaining
connectivity that compensates for a generalized synapse loss.
PMID- 29966023
TI - Coccolithophore community response along a natural CO2 gradient off Methana (SW
Saronikos Gulf, Greece, NE Mediterranean).
AB - A natural pH gradient caused by marine CO2 seeps off the Methana peninsula
(Saronikos Gulf, eastern Peloponnese peninsula) was used as a natural laboratory
to assess potential effects of ocean acidification on coccolithophores.
Coccolithophore communities were therefore investigated in plankton samples
collected during September 2011, September 2016 and March 2017. The recorded cell
concentrations were up to ~50 x103 cells/l, with a high Shannon index of up to
2.8, along a pH gradient from 7.61 to 8.18, with values being occasionally <7.
Numerous holococcolithophore species represented 60-90% of the surface water
assemblages in most samples during September samplings. Emiliania huxleyi was
present only in low relative abundances in September samples, but it dominated in
March assemblages. Neither malformed nor corroded coccolithophores were
documented. Changes in the community structure can possibly be related to
increased temperatures, while the overall trend associates low pH values with
high cell densities. Our preliminary results indicate that in long-termed
acidified, warm and stratified conditions, the study of the total coccolithophore
assemblage may prove useful to recognize the intercommunity variability, which
favors the increment of lightly calcified species such as holococcolithophores.
PMID- 29966026
TI - A light-driven molecular machine based on stiff stilbene.
AB - We report a new molecular design for optically triggered nm-scale translation of
a submolecular component relative to another. We used a rotaxane-like molecule
terminated at one end with stiff stilbene that served both as a chromophore to
trigger the translation of the pillar[5]arene "wheel" and as a stopper to prevent
its dethreading.
PMID- 29966025
TI - A thermoresponsive dynamic polymer brush fabricated by the segregation of
amphiphilic diblock copolymers.
AB - A highly dense polymer brush was previously fabricated by the spontaneous
segregation of amphiphilic diblock copolymers in an elastomer matrix into water
and a hydrophobic polymer interface and named a 'dynamic polymer brush'. We
fabricated a lower critical solution temperature (LCST)-type thermoresponsive
dynamic polymer brush by mixing polyisoprene-b-poly[tri(ethylene glycol)methyl
ether methacrylate] (PI-b-PME3MA) into a polystyrene-b-polyisoprene-b-polystyrene
(SIS) elastomer. The LCST of PME3MA in water is 52 degrees C. The structure of
the polymer brush was determined at several different temperatures using neutron
reflectivity. With increasing temperature, the brush thickness of the LCST-type
thermoresponsive dynamic polymer brush decreases, similar to the conventional
fixed brush with the LCST-type thermoresponse. However, the graft density of the
dynamic polymer brush surprisingly increases with increasing temperature. The
change of the brush density of the conventional fixed polymer brush is not
allowed. However, we observed for the first time that dynamic polymer brushes
uniquely respond to increasing temperature with increasing brush densities.
PMID- 29966024
TI - Exploring Immune Development in Infants With Moderate to Severe Atopic
Dermatitis.
AB - Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin
disease in infancy with a complex pathology. In adults, the clinical severity of
AD has been associated with increases in T helper cell type (Th) 2, Th22, and
Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and
CCL22 chemokines. Objective: To explore the possible association between serum
chemokine levels and AD severity in infants with moderate-to-severe AD and
elevated immunoglobulin E (IgE). Subjects and methods: Serum samples (n = 41)
obtained from a randomized, double-blind, and clinical dietary intervention study
were used to study biomarkers in infants with AD. Baseline- and post-intervention
samples (4 months) were used, six chemokines and nine ratios thereof were
analyzed using Luminex and correlated to AD severity. In the initial study, the
infants were randomized to receive extensively hydrolyzed whey-based formula
without (control) or with short-chain galacto-oligosaccharides/long-chain fructo
oligosaccharides (9:1) and Bifidobacterium breve M-16V (active). Results: 31
Infants up to 11 months of age, with an objective-SCORAD score (oSCORAD) >= 20
and elevated total-IgE and/or specific-IgE levels were included. In time, the
median oSCORAD decreased in both groups by -8 (control, p < 0.05; active, p <
0.01). Irrespective of dietary intervention, several changes in Th2 chemokines
(CCL17 and CCL22), inflammatory chemokine (CCL20), and the Th1 chemokine, CXC
chemokine ligand (CXCL) 9, were detected over time. Overall CCL17 correlated to
oSCORAD (r = 0.446, p < 0.01). After 4 months of dietary intervention, CXCL9 was
higher (p < 0.01) in the active group compared with control [active, 2.33 (1.99
2.89); controls, 1.95 (1.77-2.43) log 10 median (range)]. In addition, a
reduction in Th2/Th1 chemokine ratios for CCL17/CXCL9, CCL22/CXCL9, CCL20/CXCL10,
and CCL20/CXCL11 was detected associated with the active intervention.
Conclusion: While this study is small and exploratory in nature, these data
contribute to immune biomarker profiling and understanding of AD in infants.
PMID- 29966027
TI - A facile synthesis of segmented silver nanowires and enhancement of the
performance of polymer solar cells.
AB - In this work, segmented silver nanowires (AgNWs) with an average diameter of 60
nm have been successfully synthesized by a typical polyol method without any
templates and seeds. The synthesized segmented AgNWs were strongly dependent on
the reaction temperature and time. It was found from high-resolution transmission
electron microscopy and selected area electron diffraction measurements that the
connection node of segmented AgNWs was in the form of a twinned crystal. We
speculated that these segmented AgNWs were possibly derived from end-to-end self
connection and self-concrescence of two neighbouring Ag nanorods or nanowires at
a suitable reaction temperature and time, which is further confirmed by the
secondary growth of AgNWs. In addition, segmented AgNWs were blended into hole
transporting layers to enhance the performance of polymer solar cells (PSCs) by
utilizing their localized surface plasmon resonance and optical scattering
effects. As a result, the power conversion efficiency (PCE) and short-circuit
current density (Jsc) of PSCs with segmented AgNWs increased from 2.81% and 8.99
mA cm-2 to 3.30% and 9.95 mA cm-2, respectively.
PMID- 29966028
TI - Insights on magnesium and sulfate ions' adsorption on the surface of sodium
alumino-silicate hydrate (NASH) gel: a molecular dynamics study.
AB - The movement of water and ions in sodium alumino-silicate hydrate gel (NASH)
influences the physical and chemical properties of the geopolymer material. In
this paper, in order to better understand the structure and dynamics of water and
ions in the interfacial region of the NASH gel, molecular dynamics was utilized
to model Na2SO4 and MgSO4 solutions (both at 0.44 mol L-1) near the NASH surface.
The broken silicate-aluminate surface network, with predominant percentage of
randomly connected Q1 and Q2 silicate and aluminate species, provides plenty of
non-bridging oxygen sites to accept the H bond from the surface water molecules,
contributing toward a strongly adsorbed hydration layer with a thickness of
around 5 A. Consequently, the water molecule in the hydration layer exhibits
increased density, increased dipole moment magnitude, orientation preference, and
slow diffusivity. In contrast, up to 36.4% of the counter sodium ions, originally
caged in the vacancies on the NASH surface, gradually dissociate from the
silicate-aluminate skeleton and migrate into the bulk solution, which is
consistent with the experimentally observed leaching process of alkali ions in
the geopolymer material. In the MgSO4 solution, the magnesium ions-with a smaller
ionic radius-penetrate into the silicate-aluminate skeleton vacancy, have 1.8 to
2.5 coordinated solid oxygen atoms, and remain on the NASH surface for a fairly
longer time due to the stable Mg-O bonds. Mg species adsorbed on the inner sphere
got rooted onto the hydroxyl layer, healing the damaged silicate-aluminate
structures and stabilizing the network by inhibiting Na ion immigration into the
solution. Mg ions in the outer layer, on average, associated with around one
neighboring SO4 ion, forming ionic pairs and accumulating into large Mg-SO4
clusters, to help the immobilization of sulfate ions on the NASH surface.
PMID- 29966029
TI - Chemiluminescence of black phosphorus quantum dots induced by hypochlorite and
peroxide.
AB - For the first time, black phosphorus quantum dots (BP QDs) were found to show
chemiluminescence (CL) properties in the presence of hydrogen peroxide (H2O2) and
hypochlorite (ClO-). Excited phosphorus oxides (HPO) resulting from the oxidation
of BP QDs account for CL emission. Taking triacetone triperoxide (TATP) as an
example, the potential application of a new CL system was evaluated. This work
sheds new light on the characteristics and broader applications of black
phosphorus (BP).
PMID- 29966030
TI - Correction: Development of glycosynthases with broad glycan specificity for the
efficient glyco-remodeling of antibodies.
AB - Correction for 'Development of glycosynthases with broad glycan specificity for
the efficient glyco-remodeling of antibodies' by Sachin S. Shivatare et al.,
Chem. Commun., 2018, 54, 6161-6164.
PMID- 29966031
TI - A dual pH-responsive supramolecular gelator with aggregation-induced emission
properties.
AB - Functionalising AIE-active aromatic thioethers with self-complementary
zwitterionic binding sites leads to a dual pH-responsive supramolecular
organogelator with aggregation-induced emission (AIE) properties. The self
assembled fibrillar gel network is highly fluorescent (lambdaem = 490 nm),
whereas the addition of both acid and base leads to the sol state with a loss of
emission. More over, the gel was found to be thermo- and mechanoresponsive.
PMID- 29966032
TI - Effect of Hartree-Fock pseudopotentials on local density functional theory
calculations.
AB - Density functional theory (DFT) can run into serious difficulties with localized
states in elements such as transition metals with occupied d states and oxygen.
In contrast, including a fraction of the Hartree-Fock exchange can be a better
approach for such localized states. Here, we develop Hartree-Fock
pseudopotentials to be used alongside DFT for solids. The computational cost is
on a par with standard DFT. Calculations for a range of II-VI, III-V and group-IV
semiconductors with diverse physical properties show an observably improved band
gap for systems containing d-electrons, pointing to a new direction in electronic
theory.
PMID- 29966033
TI - Interrogation of spatial metabolome of Ginkgo biloba with high-resolution matrix
assisted laser desorption/ionization and laser desorption/ionization mass
spectrometry imaging.
AB - Ginkgo biloba is one of the oldest extant seed plants and has a number of unique
properties and uses. Numerous efforts have characterized metabolites within the
ginkgo plant and their corresponding biosynthesis pathways, but spatio-chemical
information on ginkgo metabolites is lacking. Mass spectrometry (MS) imaging was
used to interrogate the spatio-chemical localization of metabolites with matrix
assisted laser desorption/ionization and laser desorption/ionization Fourier
transform ion cyclotron resonance MS across the ginkgo leaf. Flavonoids,
particularly unexpected and rare flavonoid cyclodimers, were detected
predominately from leaf epidermis; ginkgolic acids and cardanols were observed
exclusively in the secretory cavities. A non-uniform distribution of flavonoids
observed between the upper and lower leaf epidermis was verified by liquid
chromatography-MS analyses. Other metabolites, such as saccharides,
phospholipids, and chlorophylls, occurred mainly in mesophyll cells. Furthermore,
organ- and tissue-specific distributions of ginkgolides were revealed in the
ginkgo root, young stem, and leaf. The acquired ion images provide important
information regarding biosynthesis, transportation, and accumulation of
metabolites throughout the ginkgo plant and should help us to understand the
physiological roles of several plant secondary metabolites.
PMID- 29966035
TI - Focused Ultrasound Enabled Trans-Blood Brain Barrier Delivery of Gold
Nanoclusters: Effect of Surface Charges and Quantification Using Positron
Emission Tomography.
AB - Focused ultrasound (FUS) technology is reported to enhance the delivery of 64 Cu
integrated ultrasmall gold nanoclusters (64 Cu-AuNCs) across the blood-brain
barrier (BBB) as measured by positron emission tomography (PET). To better define
the optimal physical properties for brain delivery, 64 Cu-AuNCs with different
surface charges are synthesized and characterized. In vivo biodistribution
studies are performed to compare the individual organ uptake of each type of 64
Cu-AuNCs. Quantitative PET imaging post-FUS treatment shows site-targeted brain
penetration, retention, and diffusion of the negative, neutral, and positive 64
Cu-AuNCs. Autoradiography is performed to compare the intrabrain distribution of
these nanoclusters. PET Imaging demonstrates the effective BBB opening and
successful delivery of 64 Cu-AuNCs into the brain. Of the three 64 Cu-AuNCs
investigated, the neutrally charged nanostructure performs the best and is the
candidate platform for future theranostic applications in neuro-oncology.
PMID- 29966034
TI - A High-Rate and Stable Quasi-Solid-State Zinc-Ion Battery with Novel 2D Layered
Zinc Orthovanadate Array.
AB - Zinc-ion batteries are under current research focus because of their uniqueness
in low cost and high safety. However, it is still desirable to improve the rate
performance by improving the Zn2+ (de)intercalation kinetics and long-cycle
stability by eliminating the dendrite formation problem. Herein, the first
paradigm of a high-rate and ultrastable flexible quasi-solid-state zinc-ion
battery is constructed from a novel 2D ultrathin layered zinc orthovanadate array
cathode, a Zn array anode supported by a conductive porous graphene foam, and a
gel electrolyte. The nanoarray structure for both electrodes assures the high
rate capability and alleviates the dendrite growth. The flexible Zn-ion battery
has a depth of discharge of ~100% for the cathode and 66% for the anode, and
delivers an impressive high-rate of 50 C (discharge in 60 s), long-term
durability of 2000 cycles at 20 C, and unprecedented energy density ~115 Wh kg-1
, together with a peak power density ~5.1 kW kg-1 (calculation includes masses of
cathode, anode, and current collectors). First principles calculations and
quantitative kinetics analysis show that the high-rate and stable properties are
correlated with the 2D fast ion-migration pathways and the introduced
intercalation pseudocapacitance.
PMID- 29966036
TI - Crystal-Face Tailored Graphitic Carbon Nitride Films for High-Performance
Photoelectrochemical Cells.
AB - Graphitic carbon nitride (g-CN) has been widely studied as a promising candidate
for water splitting, owing to its metal-free nature, moderate band gap, and low
cost. However, its photocurrent density is still very low for
photoelectrochemical cell applications. In this work, a crystal face tailored g
CN photoelectrode has been fabricated by a facile thermal vapor deposition
method. We use the melamine formaldehyde resin as a new precursor and have
successfully fabricated g-CN films. The intensity ratio between two typical peaks
(100) and (001) of g-CN is very different from that in the existing literature.
The water splitting photocurrent density is as high as 228.2 MUA cm-2 , which is
126.8 times higher than pure g-CN (1.8 MUA cm-2 ) at 1.23 V vs. reversible
hydrogen electrodes under one sun illumination without sacrificial reagents and
co-catalysts. The electrode shows the best performance, compared with the
previously reported g-CN photoelectrodes.
PMID- 29966037
TI - Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted
next-generation sequencing.
AB - BACKGROUND: Congenital diaphragmatic hernia (CDH) is characterized by a defective
closure of the diaphragm occurring as an isolated defect in 60% of cases. Lung
size, liver herniation, and pulmonary circulation are major prognostic indices.
Isolated CDH genetics is heterogeneous and poorly understood. Whether genetic
lesions are also outcome determinants has never been explored. OBJECTIVES: To
identify isolated CDH genetic causes, to fine map the mutational burden, and to
search for a correlation between the genotype and the disease severity and
outcome. METHODS: Targeted massively parallel sequencing of 143 human and mouse
CDH causative and candidate genes in a cohort of 120 fetuses with isolated CDH
and detailed outcome measures. RESULTS: Pathogenic and likely pathogenic variants
were identified in 10% of the cohort. These variants affect both known CDH
causative genes, namely, ZFPM2, GATA4, and NR2F2, and new genes, namely, TBX1,
TBX5, GATA5, and PBX1. In addition, mutation burden analysis identified LBR,
CTBP2, NSD1, MMP14, MYOD1, and EYA1 as candidate genes with enrichment in rare
but predicted deleterious variants. No obvious correlation between the genotype
and the phenotype or short-term outcome has been found. CONCLUSION: Targeted
resequencing identifies a genetic cause in 10% of isolated CDH and identifies new
candidate genes.
PMID- 29966038
TI - Evaluation of Food and Spherical Carbon Adsorbent Effects on the Pharmacokinetics
of Roxadustat in Healthy Nonelderly Adult Male Japanese Subjects.
AB - Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor in late
stage clinical development for the treatment of anemia in chronic kidney disease.
Spherical carbon adsorbent (SCA) is used in patients with chronic kidney disease
and has been shown to impact absorption of certain concomitant drugs. Two phase
1, open-label, randomized, crossover studies were conducted in healthy adult
Japanese males to investigate the effect of food and SCA on the pharmacokinetics
of a single oral dose of roxadustat. Subjects in the food effect study received a
single dose of 100-mg roxadustat under fed and fasted conditions. Subjects in the
SCA/roxadustat drug-drug interaction study received a single dose of 100-mg
roxadustat alone, concomitantly with SCA, and 1 and 2 hours before and after SCA
to consider the real-world clinical situation and assess any potential impact of
a lag time on the pharmacokinetics of roxadustat. Primary outcomes for both
studies were area under the concentration-time curve from the time of dosing
extrapolated to infinity and maximum concentration of drug in blood plasma. In
the food effect study (N = 16), the geometric mean ratio (fed/fasted) and 90%
confidence interval for area under the concentration-time curve from the time of
dosing extrapolated to infinity and maximum concentration of roxadustat were
94.44 (89.93-99.18) and 79.88 (72.09-88.52), respectively. In the SCA/roxadustat
drug-drug interaction study, all geometric mean ratios and 90% confidence
intervals (roxadustat + SCA/roxadustat) were within the no-effect boundaries of
80% and 125%. Roxadustat was generally well tolerated. The effect of food on the
pharmacokinetics of roxadustat and the drug-drug interaction between roxadustat
and SCA do not appear to be clinically relevant and support the safe use of
roxadustat under these conditions.
PMID- 29966039
TI - Copper-Vapor-Assisted Growth and Defect-Healing of Graphene on Copper Surfaces.
AB - Although there is significant progress in the chemical vapor deposition (CVD) of
graphene on Cu surfaces, the industrial application of graphene is not realized
yet. One of the most critical obstacles that limit the commercialization of
graphene is that CVD graphene contains too many vacancies or sp3 -type defects.
Therefore, further investigation of the growth mechanism is still required to
control the defects of graphene. During the growth of graphene, sublimation of
the Cu catalyst to produce Cu vapor occurs inevitably because the process
temperature is close to the melting point of Cu. However, to date few studies
have investigated the effects of Cu vapor on graphene growth. In this study, how
the Cu vapor produced by sublimation affects the chemical vapor deposition of
graphene on Cu surfaces is investigated. It is found that the presence of Cu
vapor enlarges the graphene grains and enhances the efficiency of the defect
healing of graphene by CH4 . It is elucidated that these effects are due to the
removal by Cu vapor of carbon adatoms from the Cu surface and oxygen
functionalized carbons from graphene. Finally, these insights are used to develop
a method for the synthesis of uniform and high-quality graphene.
PMID- 29966040
TI - Perinatal outcomes following cell-free DNA screening in >32 000 women: Clinical
follow-up data from a single tertiary center.
AB - OBJECTIVE: Cell-free DNA (cfDNA) screening for aneuploidy was clinically
introduced in 2011. We aim to focus on the follow-up information from a single
tertiary center undergoing genome-wide cfDNA screening to evaluate this
technology. METHOD: A total of 32 431 cases were retrospectively reviewed. The
screening was performed using a BGI protocol, and the cfDNA results were analyzed
together with the pregnancy outcomes, confirmatory testing results, and
ultrasound findings. RESULTS: Of the 32 431 cfDNA screening cases, successful
follow-up was conducted in 287 (82.2%) cases with high-risk cfDNA results, 85
(94.4%) cases with copy number variation (CNV) and rare autosomal trisomy (RAT)
results, and 26 060 (81.5%) cases with low-risk cfDNA results. Among them, 234
with high-risk cfDNA results chose invasive testing, revealing 169 true positive
cases. In cases with CNV and RAT results, 45 cases underwent invasive diagnosis,
revealing six pathogenic CNVs and three uniparental disomies. In cases with low
risk cfDNA results, three false negative cases were confirmed. CONCLUSION: Cell
free DNA screening appears to be effective in detecting the common autosomal
aneuploidies, but one-third of our cohort with high-risk results rejected
confirmatory testing. Our data provide information on the clinical experience of
large-scale whole-genome cfDNA screening that has global relevance for the
implementation of this technology.
PMID- 29966041
TI - Engineering Morphologies of Cobalt Pyrophosphates Nanostructures toward Greatly
Enhanced Electrocatalytic Performance of Oxygen Evolution Reaction.
AB - Herein, a surfactant- and additive-free strategy is developed for morphology
controllable synthesis of cobalt pyrophosphate (CoPPi) nanostructures by tuning
the concentration and ratio of the precursor solutions of Na4 P2 O7 and Co(CH3
COO)2 . A series of CoPPi nanostructures including nanowires, nanobelts,
nanoleaves, and nanorhombuses are prepared and exhibit very promising
electrocatalytic properties toward the oxygen evolution reaction (OER). Acting as
both reactant and pseudo-surfactant, the existence of excess Na4 P2 O7 is
essential to synthesize CoPPi nanostructures for unique morphologies. Among all
CoPPi nanostructures, the CoPPi nanowires catalyst renders the best catalytic
performance for OER in alkaline media, achieving a low Tafel slope of 54.1 mV dec
1 , a small overpotential of 359 mV at 10 mA cm-2 , and superior stability. The
electrocatalytic activities of CoPPi nanowires outperform the most reported non
noble metal based catalysts, even better than the benchmark Ir/C (20%) catalyst.
The reported synthesis of CoPPi gives guidance for morphology control of
transition metal pyrophosphate based nanostructures for a high-performance
inexpensive material to replace the noble metal-based OER catalysts.
PMID- 29966042
TI - Facile, Room Temperature, Electroless Deposited (Fe1-x, Mnx )OOH Nanosheets as
Advanced Catalysts: The Role of Mn Incorporation.
AB - Herein, bimetallic iron (Fe)-manganese (Mn) oxyhydroxide ((Fe1-x, Mnx )OOH,
FeMnOOH) nanosheets on fluorine-doped tin oxide conducting substrates and on
semiconductor photoanodes are synthesized by a facile, room temperature,
electroless deposition method as catalysts for both electrochemical and photo
electrochemical (PEC) water splitting, respectively. Surprisingly, Mn-doped FeOOH
can significantly modulate the nanosheet morphology to increase the active
surface area, boost more active sites, and augment the intrinsic activity by
tuning the electronic structure of FeOOH. Due to the 2D nanosheet architecture,
the optimized FeMnOOH exhibits superior electrochemical activity and outstanding
durability for the oxygen evolution reaction with a low overpotential of 246 mV
at 10 mA cm-2 and 414 mV at 100 mA cm-2 , and long-term stability for 40 h
without decay, which is comparable to the best electrocatalysts for water
oxidation reported in the literature. By integrating with semiconductor
photoanodes (such as alpha-Fe2 O3 nanorod (NR) arrays), bimetallic FeMnOOH
catalysts achieve solar-driven water splitting with a significantly enhanced PEC
performance (3.36 mA cm-2 at 1.23 V vs reversible hydrogen electrode (RHE)) with
outstanding long-term stability (~8 h) compared to that of the bare Fe2 O3 NR
(0.92 mA cm-2 at 1.23 V vs RHE).
PMID- 29966044
TI - Advanced food analysis, foodome and foodomics.
PMID- 29966045
TI - Quinone-Fused Pyrazoles through 1,3-Dipolar Cycloadditions: Synthesis of
Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma
Cancer Cells.
AB - A novel and straightforward synthesis of highly substituted isoquinoline-5,8
dione fused tricyclic pyrazoles is reported. The key step of the synthetic
sequence is a regioselective, Ag2 CO3 promoted, 1,3-dipolar cycloaddition of C
heteroaryl-N-aryl nitrilimines and substituted isoquinoline-5,8-diones. The broad
functional group tolerability and mild reaction conditions were found to be
suitable for the preparation of a small library of compounds. These scaffolds
were designed to interact with multiple biological residues, and two of them,
after brief synthetic elaborations, were analyzed by molecular docking studies as
potential anticancer drugs. In vitro studies confirmed the potent anticancer
effects, showing promising IC50 values as low as 2.5 MUm against three different
glioblastoma cell lines. Their cytotoxic activity was finally positively
correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible
for the regulation of diverse cellular processes in human cancer cells.
PMID- 29966046
TI - Prenatal chromosomal microarray uptake with invasive prenatal diagnosis: How many
patients take the leap?
AB - OBJECTIVE: Characterize the uptake of chromosomal microarray analysis (CMA) among
women undergoing invasive prenatal diagnosis at a large academic institution over
a 4-year time period. METHODS: Retrospective database review of women who
underwent invasive prenatal diagnosis via chorionic villus sampling (CVS) or
amniocentesis. Entries were reviewed for demographic and clinical information.
RESULTS: Nine hundred forty-six diagnostic procedures were performed at our
institution over a 4-year time period including 259 CVS and 687 amniocentesis
procedures. Overall, 32% elected CMA, with a significant increase in uptake over
time. Women with Medicaid/CHIP insurance were more likely to elect CMA than those
with private insurance (OR = 1.59, 95% CI, 1.18-2.14), while multigravida women
were less likely than primigravidas to elect CMA (P = 0.003). Women with
ultrasound findings were more likely to elect CMA than any other indication.
Those with structural abnormalities in multiple systems (OR = 3.75, 95% CI, 1.60
8.79) or abnormalities in a single system (OR = 3.22, 95% CI, 1.47-7.05) were
more likely to elect CMA than with any other types of ultrasound findings.
CONCLUSION: The uptake of CMA significantly increased over a 4-year period at a
large academic institution. Women with ultrasound indications, specifically
structural abnormalities, are the most likely to elect CMA.
PMID- 29966047
TI - Erratum: Application of flipped classroom pedagogy to the human gross anatomy
laboratory: Student preferences and learning outcomes.
PMID- 29966048
TI - Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting
Approaches to Positron Emission Tomography Imaging.
AB - The use of radiolabelled antibodies and antibody-derived recombinant constructs
has shown promise for both imaging and therapeutic use. In this context, the
biotin-avidin/streptavidin pairing, along with the inverse-electron-demand Diels
Alder (iEDDA) reaction, have found application in pretargeting approaches for
positron emission tomography (PET). This study reports the fluorinase-mediated
transhalogenation [5'-chloro-5'-deoxyadenosine (ClDA) substrates to 5'-fluoro-5'
deoxyadenosine (FDA) products] of two antibody pretargeting tools, a FDA-PEG
tetrazine and a [18 F]FDA-PEG-biotin, and each is assessed either for its
compatibility towards iEDDA ligation to trans-cyclooctene or for its affinity to
avidin. A protocol to avoid radiolytically promoted oxidation of biotin during
the synthesis of [18 F]FDA-PEG-biotin was developed. The study adds to the
repertoire of conjugates for use in fluorinase-catalysed radiosynthesis for PET
and shows that the fluorinase will accept a wide range of ClDA substrates
tethered at C-2 of the adenine ring with a PEGylated cargo. The method is
exceptional because the nucleophilic reaction with [18 F]fluoride takes place in
water at neutral pH and at ambient temperature.
PMID- 29966049
TI - Leading for Safety. For executives, making healthcare safe is a leadership
imperative.
PMID- 29966050
TI - AN INTERVIEW WITH ACHE's 2017-2018 Chairman.
PMID- 29966051
TI - BUILDING ON SUCCESS TO CONQUER PATIENT HARM.
PMID- 29966052
TI - Growing Your Trust Equity. New Strategies to Communicate With Patients When
Errors Occur.
PMID- 29966053
TI - Discrimination and Patient-Centered Care. Organizational best-practice guidelines
can provide ethical and legal guidance.
PMID- 29966054
TI - South Texas ACO Finds Perfect Formula. Patients' diabetes outcomes were improved
and millions of dollars saved.
PMID- 29966055
TI - A Population Health Approach to Dementia. Integrating evidence-based care with
innovative technologies.
PMID- 29966057
TI - The Ability to Change: A Core Leadership Skill. Learn to adapt in a
transformational landscape.
PMID- 29966056
TI - What's Ahead in Healthcare? The new administration favors a state-run, market
driven approach to crafting policy.
PMID- 29966058
TI - Breaking Free From Traditional Models. Some systems are embracing new governance
paradigms.
PMID- 29966059
TI - Taking a Stand Against Workplace Violence. Protecting employees and patients is a
top priority.
PMID- 29966060
TI - Leading With Compassion. A track record of success opens doors, while fostering a
culture of goodwill brings respect.
PMID- 29966061
TI - THE FUTURE OF HEALTHCARE FINANCE. Focusing Your Strategies Amid Uncertainty.
PMID- 29966062
TI - The New Strategic Imperative for Philanthropy Programs.
PMID- 29966063
TI - Patient's Plea-Look Closer, See Me. Viewing patients as unique individuals
affects attitudes and behavior.
PMID- 29966064
TI - Taking a Deeper Look at the Care Environment. Adjunct risk evaluation helps
acquiring organizations assess the patient-safety climate.
PMID- 29966065
TI - Assuaging Hunger in a Food Desert. Health system addresses social determinants of
cost and quality of care.
PMID- 29966066
TI - MACRA: An Overview and Implications. Healthcare is taking the next step on the
long road to value-based purchasing.
PMID- 29966067
TI - Considerations in the Physician Transition to Leadership. Formal training eases
the move from clinical practice to administration.
PMID- 29966068
TI - Better Care for Complex Needs. Priorities for the field emphasize experimentation
and collaboration.
PMID- 29966069
TI - A Parallel Pathway to Successful Transitions. Leadership colleagues can help new
physician leaders succeed.
PMID- 29966070
TI - 10 Ways to Build Effective Community Relations. There are many simple steps your
agency can take to develop trust and foster respect.
PMID- 29966071
TI - Can Body Cameras Improve Documentation? Medics in this pilot study were allowed
to review videos of calls and change their PCRs.
PMID- 29966072
TI - ON TH FRONT LINES: EMS AND THE BATTLE FOR MOSUL. NYCMedics is helping care for
casualties during the ongoing fighting in Iraq.
PMID- 29966073
TI - GATHERING OF EAGLES-PART I: Better Ways to Handle Familiar Problems. At this
year's conference, top medical directors offered alternative treatment ideas for
frequent and nonemergency users.
PMID- 29966074
TI - IN A PROLONGED ASTHMA ATTACK, START AT THE END. When bronchodilators aren't
working, your patient is in jeopardy.
PMID- 29966075
TI - How to Improve (and How to Tell). Key indicators can help you determine if an
improvement really enhances performance.
PMID- 29966076
TI - HOW TO USE DATA AND TECHNOLOGY in Quality Improvement and Training.
PMID- 29966077
TI - How Digital Ambulances CAN BETTER EQUIP EMS PROVIDERS. Also known as smart
ambulances, their state-of-the-art technology can improve patient care while
lowering operating costs.
PMID- 29966078
TI - A Potent Conformation-Constrained Synthetic Peptide Mimic of a Homeodomain
Selectively Regulates Target Genes in Cells.
AB - DNA, as a target for therapeutic intervention, remains largely unexplored. DLX-4,
a homeodomain containing transcription factor, and its spliced isoforms play
crucial roles in many aspects of cellular biochemistry and important roles in
many diseases. A smaller peptide mimicking the homeodomain of the transcription
factor DLX-4 was designed and synthesized by suitable conjoining of its modified
DNA-binding elements. The peptide binds to DLX-4 target sites on the regulatory
region of the globin gene cluster with native-like affinity and specificity in
vitro. When conjugated to cell penetrating and nuclear localization sequences, it
upregulated some of the genes repressed by DLX-4 or its isoforms, such as beta-
and gamma-globin genes in erythropoietin-induced differentiating CD34+ human
hematopoietic stem/progenitor cells with high specificity by competing with the
respective binding sites. Engineered peptides mimicking DNA-binding domains of
transcription factors offer the potential for creating synthetic molecules for
directly targeting DNA sites with high specificity.
PMID- 29966079
TI - Global Protein Stabilization Does Not Suffice to Prevent Amyloid Fibril
Formation.
AB - Mutations or cellular conditions that destabilize the native protein conformation
promote the population of partially unfolded conformations, which in many cases
assemble into insoluble amyloid fibrils, a process associated with multiple human
pathologies. Therefore, stabilization of protein structures is seen as an
efficient way to prevent misfolding and subsequent aggregation. This has been
suggested to be the underlying reason why proteins living in harsh environments,
such as the extracellular space, have evolved disulfide bonds. The effect of
protein disulfides on the thermodynamics and kinetics of folding has been
extensively studied, but much less is known on its effect on aggregation
reactions. Here, we designed a single point mutation that introduces a disulfide
bond in the all-alpha FF domain, a protein that, despite being devoid of
preformed beta-sheets, forms beta-sheet-rich amyloid fibrils. The novel and
unique covalent bond in the FF domain dramatically increases its thermodynamic
stability and folding speed. Nevertheless, these optimized properties cannot
counteract the inherent aggregation propensity of the protein, thus indicating
that a high global protein stabilization does not suffice to prevent amyloid
formation unless it contributes to hide from exposure the specific regions that
nucleate the aggregation reaction.
PMID- 29966080
TI - Cytochrome c Reduction by H2S Potentiates Sulfide Signaling.
AB - Hydrogen sulfide (H2S) is an endogenously produced gas that is toxic at high
concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation
pathway, which connects to the electron transfer chain at the level of complex
III. Direct reduction of cytochrome c (Cyt C) by H2S has been reported previously
but not characterized. In this study, we demonstrate that reduction of ferric Cyt
C by H2S exhibits hysteretic behavior, which suggests the involvement of reactive
sulfur species in the reduction process and is consistent with a reaction
stoichiometry of 1.5 mol of Cyt C reduced/mol of H2S oxidized. H2S increases O2
consumption by human cells (HT29 and HepG2) treated with the complex III
inhibitor antimycin A, which is consistent with the entry of sulfide-derived
electrons at the level of complex IV. Cyt C-dependent H2S oxidation stimulated
protein persulfidation in vitro, while silencing of Cyt C expression decreased
mitochondrial protein persulfidation in a cell culture. Cyt C released during
apoptosis was correlated with persulfidation of procaspase 9 and with loss of its
activity. These results reveal a potential role for the electron transfer chain
in general, and Cyt C in particular, for potentiating sulfide-based signaling.
PMID- 29966081
TI - Enhanced Intracellular Ca2+ Nanogenerator for Tumor-Specific Synergistic Therapy
via Disruption of Mitochondrial Ca2+ Homeostasis and Photothermal Therapy.
AB - Breast cancer therapy has always been a hard but urgent issue. Disruption of
mitochondrial Ca2+ homeostasis has been reported as an effective antitumor
strategy, while how to contribute to mitochondrial Ca2+ overload effectively is a
critical issue. To solve this issue, we designed and engineered a dual enhanced
Ca2+ nanogenerator (DECaNG), which can induce elevation of intracellular Ca2+
through the following three ways: Calcium phosphate (CaP)-doped hollow mesoporous
copper sulfide was the basic Ca2+ nanogenerator to generate Ca2+ directly and
persistently in the lysosomes (low pH). Near-infrared light radiation (NIR, such
as 808 nm laser) can accelerate Ca2+ generation from the basic Ca2+ nanogenerator
by disturbing the crystal lattice of hollow mesoporous copper sulfide via NIR
induced heat. Curcumin can facilitate Ca2+ release from the endoplasmic reticulum
to cytoplasm and inhibit expelling of Ca2+ in cytoplasm through the cytoplasmic
membrane. The in vitro study showed that DECaNG could produce a large amount of
Ca2+ directly and persistently to flow to mitochondria, leading to upregulation
of Caspase-3, cytochrome c, and downregulation of Bcl-2 and ATP followed by cell
apoptosis. In addition, DECaNG had an outstanding photothermal effect.
Interestingly, it was found that DECaNG exerted a stronger photothermal effect at
lower pH due to the super small nanoparticles effect, thus enhancing photothermal
therapy. In the in vivo study, the nanoplatform had good tumor targeting and
treatment efficacy via a combination of disruption of mitochondrial Ca2+
homeostasis and photothermal therapy. The metabolism of CaNG was sped up through
disintegration of CaNG into smaller nanoparticles, reducing the retention time of
the nanoplatform in vivo. Therefore, DECaNG can be a promising drug delivery
system for breast cancer therapy.
PMID- 29966082
TI - Reversible Fusion Proteins as a Tool to Enhance Uptake of Virus-Functionalized
LbL Microcarriers.
AB - For the efficient treatment of an increasing number of diseases the development
of new therapeutics as well as novel drug delivery systems is essential. Such
drug delivery systems (DDS) must not only consider biodegradability and
protective packaging but must also target and control the release of active
substances, which is one of the most important points in DDS application. We
highlight the improvement of these key aspects, the increased interaction rate of
Layer-by-Layer (LbL) designed microcarriers as a promising DDS after
functionalization with vesicular stomatitis virus (VSV). We make use of the
unique conformational reversibility of the fusion protein of VSV as a surface
functionalization of LbL microcarriers. This reversibility allows for VSV to be
used both as a tool for assembly onto the DDS and as an initiator for an
efficient cellular uptake. We could show that the evolutionary optimized viral
fusion machinery can be successfully combined with a biophysical DDS for
optimization of its cellular interaction.
PMID- 29966083
TI - Fluorinated Gold Nanoparticles for Nanostructure Imaging Mass Spectrometry.
AB - Nanostructure imaging mass spectrometry (NIMS) with fluorinated gold
nanoparticles (f-AuNPs) is a nanoparticle assisted laser desorption/ionization
approach that requires low laser energy and has demonstrated high sensitivity.
Here we describe NIMS with f-AuNPs for the comprehensive analysis of metabolites
in biological tissues. F-AuNPs assist in desorption/ionization by laser-induced
release of the fluorocarbon chains with minimal background noise. Since the
energy barrier required to release the fluorocarbons from the AuNPs is minimal,
the energy of the laser is maintained in the low MUJ/pulse range, thus limiting
metabolite in-source fragmentation. Electron microscopy analysis of tissue
samples after f-AuNP NIMS shows a distinct "raising" of the surface as compared
to matrix assisted laser desorption ionization ablation, indicative of a gentle
desorption mechanism aiding in the generation of intact molecular ions. Moreover,
the use of perfluorohexane to distribute the f-AuNPs on the tissue creates a
hydrophobic environment minimizing metabolite solubilization and spatial
dislocation. The transfer of the energy from the incident laser to the analytes
through the release of the fluorocarbon chains similarly enhances the
desorption/ionization of metabolites of different chemical nature, resulting in
heterogeneous metabolome coverage. We performed the approach in a comparative
study of the colon of mice exposed to three different diets. F-AuNP NIMS allows
the direct detection of carbohydrates, lipids, bile acids, sulfur metabolites,
amino acids, nucleotide precursors as well as other small molecules of varied
biological origins. Ultimately, the diversified molecular coverage obtained
provides a broad picture of a tissue's metabolic organization.
PMID- 29966084
TI - Firefly Algorithm Applied to Noncollinear Magnetic Phase Materials Prediction.
AB - In most noncollinear crystal magnets, the number of metastable states is quite
large and any calculation that tries to predict the ground state can fall into
one of the possible metastable phases. In this work, we generalize the population
based meta-heuristic firefly algorithm to the problem of the noncollinear
magnetic phase ground state prediction within density functional theory (DFT). We
extend the different steps in the firefly algorithm to this specific problem by
using polarized constrained DFT calculations, whereby using Lagrange multipliers
the directions of the atom magnetic moments remain fixed. By locking the
directions of the magnetic moments at each search iteration, the method allows
one to explore the entire Born-Oppenheimer energy surface of existing and
physically plausible noncollinear configurations present in a crystal. We
demonstrate that the number of minima can be large, which restrains the use of
exhaustive searches.
PMID- 29966085
TI - C-Methylation Catalyzed by Fom3, a Cobalamin-Dependent Radical S-adenosyl-l
methionine Enzyme in Fosfomycin Biosynthesis, Proceeds with Inversion of
Configuration.
AB - Fom3, a cobalamin-dependent radical S-adenosyl-l-methionine (SAM)
methyltransferase, catalyzes C-methylation at the C2 position of cytidylylated 2
hydroxyethylphosphonate (HEP-CMP) to afford cytidylylated 2
hydroxypropylphosphonate (HPP-CMP) in fosfomycin biosynthesis. In this study, the
Fom3 reaction product HPP-CMP was reanalyzed by chiral ligand exchange
chromatography to confirm its stereochemistry. The Fom3 methylation product was
found to be ( S)-HPP-CMP only, indicating that the stereochemistry of the C
methylation catalyzed by Fom3 is ( S)-selective. In addition, Fom3 reaction was
performed with ( S)-[2-2H1]HEP-CMP and ( R)-[2-2H1]HEP-CMP to elucidate the
stereoselectivity during the abstraction of the hydrogen atom from C2 of HEP-CMP.
Liquid chromatography-electrospray ionization mass spectrometry analysis of the
5'-deoxyadenosine produced showed that the 2H atom of ( R)-[2-2H1]HEP-CMP was
incorporated into 5'-deoxyadenosine but that from ( S)-[2-2H1]HEP-CMP was not.
Retention of the 2H atom of ( S)-[2-2H1]HEP-CMP in HPP-CMP was also observed.
These results indicate that the 5'-deoxyadenosyl radical stereoselectively
abstracts the pro-R hydrogen atom at the C2 position of HEP-CMP and the substrate
radical intermediate reacts with the methyl group on cobalamin that is located on
the opposite side of the substrate from SAM. Consequently, it was clarified that
the C-methylation catalyzed by Fom3 proceeds with inversion of configuration.
PMID- 29966086
TI - Activation of Surface Oxygen Sites in a Cobalt-Based Perovskite Model Catalyst
for CO Oxidation.
AB - Anionic redox chemistry is becoming increasingly important in explaining the
intristic catalytic behavior in transition-metal oxides and improving catalytic
activity. However, it is a great challenge to activate lattice oxygen in noble
metal-free perovskites for obtaining active peroxide species. Here, we take
La0.4Sr0.6CoO3-delta as a model catalyst and develop an anionic redox activity
regulation method to activate lattice oxygen by tuning charge transfer between
Co4+ and O2-. Advanced XAS and XPS demonstrate that our method can effectively
decrease electron density of surface oxygen sites (O2-) to form more reactive
oxygen species (O2- x), which reduces the activation energy barriers of molecular
O2 and leads to a very high CO catalytic activity. The revealing of the
activation mechanism for surface oxygen sites in perovskites in this work opens
up a new avenue to design efficient solid catalysts. Furthermore, we also
establish a correlation between anionic redox chemistry and CO catalytic
activity.
PMID- 29966087
TI - Transferable MARTINI Model of Poly(ethylene Oxide).
AB - Motivated by the deficiencies of the previous MARTINI models of poly(ethylene
oxide) (PEO), we present a new model featuring a high degree of transferability.
The model is parametrized on (a) a set of 8 free energies of transfer of
dimethoxyethane (PEO dimer) from water to solvents of varying polarity; (b) the
radius of gyration in water at high dilution; and (c) matching angle and dihedral
distributions from atomistic simulations. We demonstrate that our model behaves
well in five different areas of application: (1) it produces accurate densities
and phase behavior or small PEO oligomers and water mixtures; (2) it yields chain
dimensions in good agreement with the experiment in three different solvents
(water, diglyme, and benzene) over a broad range of molecular weights (~1.2
kg/mol to 21 kg/mol); (3) it reproduces qualitatively the structural features of
lipid bilayers containing PEGylated lipids in the brush and mushroom regime; (4)
it is able to reproduce the phase behavior of several PEO-based nonionic
surfactants in water; and (5) it can be combined with the existing MARTINI PS to
model PS-PEO block copolymers. Overall, the new PEO model outperforms previous
models and features a high degree of transferability.
PMID- 29966088
TI - A Revised Mechanism for the Kinugasa Reaction.
AB - Detailed kinetic analysis for the Cu(I)-catalyzed Kinugasa reaction forming beta
lactams has revealed an anomalous overall zero-order reaction profile, due to
opposing positive and negative orders in nitrone and alkyne, respectively.
Furthermore, the reaction displays a second-order dependence on the catalyst,
confirming the critical involvement of a postulated bis-Cu complex. Finally,
reaction progress analysis of multiple byproducts has allowed a new mechanism,
involving a common ketene intermediate to be delineated. Our results demonstrate
that beta-lactam synthesis through the Kinugasa reaction proceeds via a cascade
involving (3 + 2) cycloaddition, (3 + 2) cycloreversion, and finally (2 + 2)
cycloaddition. Our new mechanistic understanding has resulted in optimized
reaction conditions to dramatically improve the yield of the target beta-lactams
and provides the first consistent mechanistic model to account for the formation
of all common byproducts of the Kinugasa reaction.
PMID- 29966089
TI - Oxide-Carbon Nanofibrous Composite Support for a Highly Active and Stable Polymer
Electrolyte Membrane Fuel-Cell Catalyst.
AB - Well-designed electronic configurations and structural properties of
electrocatalyst alter the activity, stability, and mass transport for enhanced
catalytic reactions. We introduce a nanofibrous oxide-carbon composite by an in
situ method of carbon nanofiber (CNF) growth by highly dispersed Ni nanoparticles
that are exsoluted from a NiTiO3 surface. The nanofibrous feature has a 3D web
structure with improved mass-transfer properties at the electrode. In addition,
the design of the CNF/TiO2 support allows for complex properties for excellent
stability and activity from the TiO2 oxide support and high electric conductivity
through the connected CNF, respectively. Developed CNF/TiO2-Pt nanofibrous
catalyst displays exemplary oxygen-reduction reaction (ORR) activity with
significant improvement of the electrochemical surface area. Moreover,
exceptional resistance to carbon corrosion and Pt dissolution is proven by
durability-test protocols based on the Department of Energy. These results are
well-reflected to the single-cell tests with even-better performance at the
kinetic zone compared to the commercial Pt/C under different operation
conditions. CNF/TiO2-Pt displays an enhanced active state due to the strong
synergetic interactions, which decrease the Pt d-band vacancy by electron
transfer from the oxide-carbon support. A distinct reaction mechanism is also
proposed and eventually demonstrates a promising example of an ORR
electrocatalyst design.
PMID- 29966090
TI - A New Concept of Promoting Nitrate Reduction in Surface Waters: Simultaneous
Supplement of Denitrifiers, Electron Donor Pool, and Electron Mediators.
AB - The efficiency of biological nitrate reduction depends on the community
composition of microorganisms, the electron donor pool, and the electron
mediators participating in the biological reduction process. This study aims at
creating an in situ system comprising of denitrifiers, electron donors, and
electron mediators to reduce nitrate in surface waters. The ubiquitous periphytic
biofilm in waters was employed to promote in situ nitrate reduction in the
presence of titanium dioxide (TiO2) nanoparticles (NPs). The nitrate removal rate
in the periphytic biofilm and TiO2 NPs system was significantly higher than the
control (only periphytic biofilm or TiO2 NPs). TiO2 NPs optimized the community
composition of periphytic biofilm for nitrate reduction by increasing the
relative abundance of four dominant denitrifying bacteria. Periphytic biofilm
showed a substantial increase in extracellular polymeric substance, especially
the humic acid and protein content, due to the presence of TiO2 NPs. The
synergistic action of humic acid, protein, denitrifying bacteria of the
periphytic biofilm, and TiO2 NPs contributed to 80% of the nitrate reduction. The
protein and humic acid, acting as electron mediators, facilitated the transfer of
exogenous electrons from photoexcited TiO2 NPs to periphytic biofilm containing
denitrifiers, which enhanced nitrate reduction in surface waters.
PMID- 29966091
TI - Ultralong Room-Temperature Phosphorescence from Supramolecular Behavior via
Intermolecular Electronic Coupling in Pure Organic Crystals.
AB - Ultralong room-temperature phosphorescence (RTP) of organic materials is
extremely attractive for its tremendous potential use. However, the design of
organic materials with ultralong and efficient RTP is very challenging due to the
lack of general design principles. A new design principle for organic materials
with ultralong room-temperature phosphorescence based on pi-pi-dominated
supramolecular aggregates in crystal is proposed, and strong intermolecular
electronic coupling with specific molecular alignment is identified to be
responsible for supramolecular behavior in persistent emission. Small
substituents in molecular structure favor the formation of supramolecular
aggregates in the crystal, thus facilitating the generation of ultralong RTP
under ambient conditions. Our results also reveal that the introduction of heavy
atoms into supramolecular aggregates as a general rule can be used to achieve
efficient persistent phosphorescence.
PMID- 29966092
TI - Visible-Light-Mediated Metal-Free Synthesis of Aryl Phosphonates: Synthetic and
Mechanistic Investigations.
AB - This work describes a straightforward access to a large variety of aryl
phosphonates by the simple combination of diaryliodonium salts with phosphites in
the presence of a base and under visible-light illumination. The reaction
proceeds smoothly, tolerates various functionalities, and was applied for the
synthesis of pharmaceutically relevant compounds. Mechanistic investigations,
including EPR, NMR, and DFT calculations, support the postulated reaction
mechanism.
PMID- 29966093
TI - Super-Radiant Emission from Quantum Dots in a Nanophotonic Waveguide.
AB - Future scalable photonic quantum information processing relies on the ability of
integrating multiple interacting quantum emitters into a single chip. Quantum
dots provide ideal on-chip quantum light sources. However, achieving quantum
interaction between multiple quantum dots on-a-chip is a challenging task due to
the randomness in their frequency and position, requiring local tuning technique
and long-range quantum interaction. Here, we demonstrate quantum interactions
between separated two quantum dots on a nanophotonic waveguide. We achieve a
photon-mediated long-range interaction by integrating the quantum dots to the
same optical mode of a nanophotonic waveguide and overcome spectral mismatch by
incorporating on-chip thermal tuners. We observe their quantum interactions of
the form of super-radiant emission, where the two dots collectively emit faster
than each dot individually. Creating super-radiant emission from integrated
quantum emitters could enable compact chip-integrated photonic structures that
exhibit long-range quantum interactions. Therefore, these results represent a
major step toward establishing photonic quantum information processors composed
of multiple interacting quantum emitters on a semiconductor chip.
PMID- 29966094
TI - Deciphering the Inhibition of the Neuronal Calcium Sensor 1 and the Guanine
Exchange Factor Ric8a with a Small Phenothiazine Molecule for the Rational
Generation of Therapeutic Synapse Function Regulators.
AB - Protein-protein interactions (PPIs) are known to play an essential role between
the neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor Ric8a to
regulate synapse function, emerging as a druggable interface for synaptopathies
such as the fragile X syndrome (FXS). Recently, the phenothiazine FD44 has been
identified as an inhibitor of this PPI, decreasing the abnormally high synapse
number and enhancing associative learning in a FXS animal model. Here, we have
integrated advanced experimental and computational studies to obtain important
structural insights into Drosophila NCS-1/FD44 recognition to understand the
basis of its affinity and specificity and generate improved PPI regulators. This
has allowed the identification of a new small drug-like molecule, IGS-1.76, which
efficiently inhibits the human NCS-1/Ric8a complex with improved binding potency.
The crystal structure of the Drosophila NCS-1/IGS-1.76 complex demonstrates that
the new inhibitor, although chemically different from FD44, shares the same
mechanism of action and constitutes a new hit candidate for FXS.
PMID- 29966095
TI - Selective Small Molecule Recognition of RNA Base Pairs.
AB - Many types of RNAs exist in the human transcriptome, yet only the bacterial
ribosome has been exploited as a small molecule drug target. Aside from rRNA,
other cellular RNAs such as noncoding RNAs have primarily secondary structure and
limited tertiary structure. Within these secondary structures of noncanonically
paired and unpaired regions, more than 50% are base paired, with most efforts to
target these structures focused on looped regions. A void exists in the
availability of small molecules capable of targeting RNA base pairs. Using
chemoinformatics, an RNA-focused library enriched for nitrogen-containing
heterocycles was developed and tested for binding RNA base pairs, leading to the
identification of six selective and previously unknown binders. While all binders
were derivatives of benzimidazoles, those with expanded aromatic polycycles bound
selectively to AU pairs, while those with flexible urea side chains bound
selectively to GC pairs. Two of the three selective GC pair binders can
distinguish between two different orientations, 5'GG/3'CC and 5'GC/3'CG pairs.
Furthermore, all six molecules showed >50-fold selectivity for RNA over DNA.
These studies provide foundational knowledge to better exploit RNA as targets for
small molecule chemical probes or lead therapeutics by using modules that target
RNA base pairs.
PMID- 29966096
TI - Asymmetric [3 + 2] Cycloaddition Reaction of Isatin-Derived MBH Carbonates with 3
Methyleneoxindoles: Enantioselective Synthesis of 3,3'
Cyclopentenyldispirooxindoles Incorporating Two Adjacent Quaternary
Spirostereocenters.
AB - A highly regio- and stereoselective [3 + 2] cycloaddition reaction for
constructing novel 3,3'-cyclopentenyldispirooxindoles incorporating two adjacent
quaternary spirostereocenters is reported. Under the mild conditions, the
asymmetric annulation of isatin-derived MBH carbonates with 3-methyleneoxindoles
involving a chiral tertiary amine catalyst provides the corresponding
dispirooxindole frameworks with an extraordinary level of enantioselective
control. Further synthetic utility of this method was demonstrated by the gram
scale experiment and simple transformation of the obtained product. Moreover, a
plausible mechanism for this annulation reaction was also proposed on the basis
of the control experiments.
PMID- 29966097
TI - Library of Synthetic Streptomyces Regulatory Sequences for Use in Promoter
Engineering of Natural Product Biosynthetic Gene Clusters.
AB - Promoter engineering has emerged as a powerful tool to activate transcriptionally
silent natural product biosynthetic gene clusters found in bacterial genomes.
Since biosynthetic gene clusters are composed of multiple operons, their promoter
engineering requires the use of a set of regulatory sequences with a similar
level of activities. Although several successful examples of promoter engineering
have been reported, its widespread use has been limited due to the lack of a
library of regulatory sequences suitable for use in promoter engineering of
large, multiple operon-containing biosynthetic gene clusters. Here, we present
the construction of a library of constitutively active, synthetic Streptomyces
regulatory sequences. The promoter assay system has been developed using a single
module nonribosomal peptide synthetase that produces the peptide blue pigment
indigoidine, allowing for the rapid screening of a large pool of regulatory
sequences. The highly randomized regulatory sequences in both promoter and
ribosome binding site regions were screened for their ability to produce the blue
pigment, and they are classified into the strong, medium, and weak regulatory
sequences based on the strength of a blue color. We demonstrated the utility of
our synthetic regulatory sequences for promoter engineering of natural product
biosynthetic gene clusters using the actinorhodin gene cluster as a model
cluster. We believe that the set of Streptomyces regulatory sequences we report
here will facilitate the discovery of new natural products from silent, cryptic
biosynthetic gene clusters found in sequenced Streptomyces genomes.
PMID- 29966099
TI - Targeting the Myofibroblast in Pulmonary Fibrosis.
PMID- 29966098
TI - A Mountaineering Strategy to Excited States: Highly Accurate Reference Energies
and Benchmarks.
AB - Striving to define very accurate vertical transition energies, we perform both
high-level coupled cluster (CC) calculations (up to CCSDTQP) and selected
configuration interaction (sCI) calculations (up to several millions of
determinants) for 18 small compounds (water, hydrogen sulfide, ammonia, hydrogen
chloride, dinitrogen, carbon monoxide, acetylene, ethylene, formaldehyde,
methanimine, thioformaldehyde, acetaldehyde, cyclopropene, diazomethane,
formamide, ketene, nitrosomethane, and the smallest streptocyanine). By
systematically increasing the order of the CC expansion, the number of
determinants in the CI expansion as well as the size of the one-electron basis
set, we have been able to reach near full CI (FCI) quality transition energies.
These calculations are carried out on CC3/ aug-cc-pVTZ geometries, using a series
of increasingly large atomic basis sets systematically including diffuse
functions. In this way, we define a list of 110 transition energies for states of
various characters (valence, Rydberg, n -> pi*, pi -> pi*, singlet, triplet,
etc.) to be used as references for further calculations. Benchmark transition
energies are provided at the aug-cc-pVTZ level as well as with additional basis
set corrections, in order to obtain results close to the complete basis set
limit. These reference data are used to benchmark a series of 12 excited-state
wave function methods accounting for double and triple contributions, namely
ADC(2), ADC(3), CIS(D), CIS(Dinfinity), CC2, STEOM-CCSD, CCSD, CCSDR(3), CCSDT-3,
CC3, CCSDT., and CCSDTQ. It turns out that CCSDTQ yields a negligible difference
with the extrapolated CI values with a mean absolute error as small as 0.01 eV,
whereas the coupled cluster approaches including iterative triples are also very
accurate (mean absolute error of 0.03 eV). Consequently, CCSDT-3 and CC3 can be
used to define reliable benchmarks. This observation does not hold for ADC(3)
that delivers quite large errors for this set of small compounds, with a clear
tendency to overcorrect its second-order version, ADC(2). Finally, we discuss the
possibility to use basis set extrapolation approaches so as to tackle more easily
larger compounds.
PMID- 29966100
TI - Protecting the Ventilated Lung: Vascular Surge and Deflation Energetics.
PMID- 29966101
TI - Lung Cancer: Advances and Insights in Diagnosis, Treatment, and Palliation.
PMID- 29966105
TI - Hemochromatosis: pathophysiology, evaluation, and management of hepatic iron
overload with a focus on MRI.
AB - INTRODUCTION: Hereditary hemochromatosis (HH) is an autosomal recessive disorder
that occurs in approximately 1 in 200-250 individuals. Mutations in the HFE gene
lead to excess iron absorption. Excess iron in the form of non-transferrin-bound
iron (NTBI) causes injury and is readily uptaken by cardiomyocytes, pancreatic
islet cells, and hepatocytes. Symptoms greatly vary among patients and include
fatigue, abdominal pain, arthralgias, impotence, decreased libido, diabetes, and
heart failure. Untreated hemochromatosis can lead to chronic liver disease,
fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Many invasive and
noninvasive diagnostic tests are available to aid in diagnosis and treatment. MRI
has emerged as the reference standard imaging modality for the detection and
quantification of hepatic iron deposition, as ultrasound (US) is unable to detect
iron overload and computed tomography (CT) findings are nonspecific and
influenced by multiple confounding variables. If caught and treated early, HH
disease progression can significantly be altered. Area covered: The data on
Hemochromatosis, iron overload, and MRI were gathered by searching PubMed. Expert
commentary: MRI is a great tool for diagnosis and management of iron overload. It
is safe, effective, and a standard protocol should be included in diagnostic
algorithms of future treatment guidelines.
PMID- 29966106
TI - The origins of cardiopulmonary bypass.
PMID- 29966107
TI - Late, transient return of pulsatility: should we change donation after
circulatory death protocols?
PMID- 29966108
TI - The use of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE)
for pre-oxygenation in neurosurgical patients: a randomised controlled trial.
AB - This study explored the use of high-flow nasal oxygen (HFNO) in both pre
oxygenation and apnoeic oxygenation in adults who were intubated following a non
rapid sequence induction. Fifty patients were randomised to receive pre
oxygenation via a standard facemask or the Transnasal Humidified Rapid
Insufflation Ventilatory Exchange (THRIVE) device. After five minutes of pre
oxygenation, induction and muscle relaxant agents were given. While waiting for
complete paralysis, patients in the standard facemask group received bag-mask
ventilation (BMV), whereas patients in the HFNO group received apnoeic
oxygenation via the THRIVE device. Serial blood samples for arterial blood gas
analysis were taken. Baseline patient and airway characteristics were similar.
The median PaO2 after pre-oxygenation was 357 (interquartile range
[IQR] 324-450 [range 183-550]) mmHg in the facemask group, compared to 471 (IQR
429-516 [range 185-550]) mmHg in the HFNO group (P=0.01). The median
arterial partial pressure of oxygen (PaO2) in the HFNO group decreased
after a period of apnoeic oxygenation, and was significantly lower when compared
to patients who received BMV in facemask group. The arterial carbon dioxide
partial pressure (PaCO2) level after complete paralysis was
significantly higher in the HFNO group when compared to the facemask group
(median 52 [IQR 48-55 {range 40-65}] versus median 43 [IQR 40-48 {range 35-63}]
mmHg, P=0.0005 and P=0.004 respectively). There were no differences
in the time to muscle paralysis and time to intubation. Seven patients required
use of airway adjuncts during BMV in the facemask group, compared to none in the
HFNO group (P=0.004). No complications were observed in either group. HFNO
produces a higher PaO2 after pre-oxygenation and safe PaO2
during intubation. However, the subsequent fall in PaO2 and rise in
PaCO2 indicates that it is not as effective as BMV in maintaining
oxygenation and ventilation following neuromuscular blockade.
PMID- 29966109
TI - The incidence of hyperthermia during craniotomy.
AB - There is evidence that even mild hyperthermia may exacerbate brain injury. There
seem reasonable grounds for considering patients undergoing craniotomy as at risk
for brain injury. A retrospective observational study was undertaken to measure
the incidence of mild hyperthermia in craniotomy cases in which the patient was
initially normothermic. Auckland City Hospital's database of electronic
anaesthetic records was searched for adult patients who were normothermic (<=37
degrees C) prior to undergoing craniotomy procedures. For each case, demographic
data, intraoperative naso- or oropharyngeal temperature measurements, and
paracetamol use were extracted. We identified the proportion of patients whose
temperature rose to exceed normal (>37 degrees C) and subdivided that group into
the proportion in whom the temperature rose to >=38 degrees C. Two thousand, nine
hundred and thirty-five craniotomy cases began their operations while
normothermic and had adequate temperature data collected. There were 984 (33.5%)
cases that had at least one temperature reading >37 degrees C, for a mean
(standard deviation [SD]) time of 66.0 (64.6) minutes, and 49 (1.7%) cases that
had at least one reading >=38 degrees C for a mean (SD) time of 40.4 (38.1)
minutes. The majority (77.8%) who became mildly hyperthermic remained so at the
end of the procedure. New mild hyperthermia occurs commonly during craniotomy. In
view of the compelling evidence of potential harm arising from mild hyperthermia
in brain injury, these findings suggest an opportunity for practice improvement
in the anaesthetic management of craniotomy patients. Reasonable steps should be
taken by anaesthetists to avoid intraoperative hyperthermia of any degree.
PMID- 29966110
TI - Optimised dosing of vancomycin in critically ill Indigenous Australian patients
with severe sepsis.
AB - Vancomycin is a commonly used antibiotic due to the high burden of methicillin
resistant Staphylococcus aureus infections. This study aimed to describe
the pharmacokinetics (PK) of vancomycin in Australian Indigenous patients with
severe sepsis, and advise an optimal dosing strategy. A population PK study was
conducted in a remote Australian intensive care unit (ICU). Serial plasma samples
were collected over one to two dosing intervals and assayed by validated
chromatography. Concentration-time data collected were analysed using Pmetrics(r)
software. The final population PK model was then used for Monte Carlo dosing
simulations to determine optimal loading and intermittent maintenance doses.
Fifteen Indigenous subjects were included for analysis with a median
(interquartile range, IQR) age, weight and creatinine clearance (CrCL) of 43 (34
46) years, 73 (66-104) kg and 99 (56-139) ml/minute respectively. A two
compartment model described the data adequately. Vancomycin clearance (CL) and
volume of distribution of the central compartment (Vc) were described by CrCL and
patient weight respectively. Median (IQR) CL, Vc, distribution rate constants
from central to peripheral, and from peripheral to central compartments were 4.6
(3.8-5.6) litres per hour, 25.4 (16.1-31.3) litres, 0.46 (0.28-0.52)/hour and
0.25 (0.12-0.37)/hour respectively. No significant interethnic PK differences
were observed in comparison to published data. Therapeutic loading doses were
significantly dependent on both weight and CrCL, whereas maintenance doses were
dependent on CrCL. In the absence of severe renal impairment, initiation of
maintenance dose eight hours post-loading dose achieved higher probability of
target attainment at 24 hours. This is the first report of vancomycin PK in this
patient group.
PMID- 29966111
TI - A prospective observational study of the change in systemic ionised calcium
following 4% citrate locking of venous haemodialysis catheters in intensive care
patients.
AB - Traditionally heparin has been the anticoagulant of choice for venous dialysis
catheter locking. There is systemic leakage of heparin catheter locking solutions
at the time of injection. Alternative agents, such as citrate, are increasingly
being used. We are not aware of any data in the critical care literature on the
effect of citrate locking of venous dialysis catheters on systemic ionised
calcium (iCa2+). To assess the effect of 4% citrate locking of venous dialysis
catheters on systemic iCa2+ in intensive care patients we performed a prospective
observational study of 50 paired samples in 26 intensive care patients receiving
4% citrate dialysis catheter locking in an adult tertiary intensive care unit
between May 2016 and December 2016. Arterial blood gas (ABG) analysis was
performed prior to venous dialysis catheter locking and a baseline iCa2+ result
obtained. The catheter was locked with 4% citrate solution. A further ABG was
sampled between 30 and 120 seconds later and the iCa2+ results were compared.
Patients were observed for clinical signs of hypocalcaemia. On average, there was
little difference between the pre- and post-catheter locking iCa2+ (median pre
locking iCa2+ 1.19 mmol/l, mean change of +0.004 mmol/l, 95% confidence interval
[CI] -0.004 to 0.013, P=0.34). There was no evidence this difference differed by
length of catheter P=0.26) or site of catheter P=0.85) insertion, but there was
some evidence that this differed by receipt of citrate dialysis circuit
anticoagulation P=0.013). Patients who received citrate dialysis circuit
anticoagulation had an increase in catheter locking iCa2+ by 0.017 mmol/l (95% CI
0.00 to 0.028). Locking of venous dialysis catheters with 4% citrate solution has
no clinically significant effect on systemic iCa2+ in intensive care patients
with indwelling venous dialysis catheters.
PMID- 29966112
TI - Intravenous tranexamic acid and lower limb arthroplasty-a randomised controlled
feasibility study.
AB - Tranexamic acid (TA) is widely reported to reduce bleeding and the risk of blood
transfusion in patients undergoing lower limb arthroplasty. No study in this
setting has had adequate power to examine for the effect of TA on either
uncommon, but clinically important, adverse events or patient-centric endpoints.
A large randomised controlled trial (RCT) is required to address these questions.
As a preliminary feasibility study, we conducted an investigator-initiated,
prospective, randomised, double blind placebo-controlled trial in 140 patients,
aged 45 years or older, undergoing elective primary or revision hip or knee joint
replacement. Subjects were randomised to receive intravenous (IV) TA or a
placebo. The primary endpoints were the proportion of patients receiving
allogenic blood transfusion and the feasibility of extending our trial
methodology to a large trial of TA in this population. Secondary endpoints
included a range of adverse clinical and surgical events as well as several
patient-centric questionnaires. Red blood cell transfusion occurred in 15% of all
patients prior to discharge from hospital. Transfusion rates were significantly
different between the TA and placebo groups (8.5% versus 21.7%, P=0.03).
Three out of four feasibility endpoints were met, with recruitment being slower
than expected. No significant differences were seen between groups in the
secondary endpoints. Despite a lower rate of transfusion than that widely
reported, IV TA reduced transfusion in patients undergoing lower limb
arthroplasty. Our trial methodology would be feasible in the setting of a large
multicentre study to investigate whether TA is safe and reduces bleeding in lower
limb arthroplasty.
PMID- 29966113
TI - The safety of anaesthetising biochemically hyperthyroid patients undergoing
thyroidectomy-a retrospective cohort study.
AB - Traditionally it is recommended that hyperthyroid patients should be made
euthyroid prior to thyroidectomy. However, several small observational studies
have reported no increase in adverse events when hyperthyroid patients undergo
thyroidectomy. The aim of this study was to assess outcomes following total
thyroidectomy in patients who were biochemically hyperthyroid at the time of
surgery compared to those who were euthyroid. One hundred and fifty-one eligible
patients undergoing thyroidectomy for hyperthyroidism between January 2012 and
February 2016 were identified, of whom 57 were hyperthyroid on perioperative
blood tests and 94 were euthyroid (comparison group). Primary outcomes were 30
day mortality, increased length of postoperative hospital stay and intraoperative
signs consistent with thyrotoxicosis (e.g. heart rate >100 per minute, systolic
blood pressure >180 or <60 mmHg, or temperature >38 degrees C). Secondary
outcomes were intraoperative beta-blocker use and level of care required
postoperatively. Thirty-day mortality was zero. The only significant difference
between the two groups was a higher use of intraoperative beta-blockers amongst
hyperthyroid patients (28.1% versus 8.5%, P=0.002). Our findings suggest
that thyroidectomy for mild to moderate biochemical hyperthyroidism performed by
an experienced thyroid surgeon and anaesthetist, is associated with increased
intraoperative beta-blocker use but no statistical difference in mortality,
length of postoperative stay or intraoperative signs consistent with
thyrotoxicosis. While we still recommend attempting to achieve a euthyroid state
whenever possible prior to thyroid surgery, mild to moderate degrees of residual
biochemical hyperthyroidism when appropriately managed may not be associated with
an increase in adverse outcomes.
PMID- 29966114
TI - Audit of ten years of donation after circulatory death experience in Queensland:
observations of agonal physiology following withdrawal of cardiorespiratory
support.
AB - An audit of ten years' experience in all patients undergoing withdrawal of
cardiorespiratory support (WCRS) in the context of donation after circulatory
death (DCD) was conducted in Queensland, Australia (2008 to 2017). One hundred
and seventy-one patients proceeded to donation after declaration of death by
circulatory criteria with loss of pulsatile arterial blood pressure (circulatory
arrest) for five minutes. The demographics, times and haemodynamic observations
were abstracted, de-identified and collated. The average age of patients was 43
years (standard deviation 16.1 years) and 63% were male. The median and mean
times to an agonal systolic blood pressure below 50 mmHg were 10 and 11 minutes
and the median and mean times from WCRS to circulatory arrest were 14 and 16
minutes. After systolic blood pressure fell to 50 mmHg or lower, 33 patients
(19.3%) had spontaneous return of systolic pressure to above 50 mmHg. Following
periods of circulatory arrest, five patients were documented to have spontaneous
return of pulsatile arterial pressure. Two patients had return of circulation
after two minutes, but less than five minutes of circulatory arrest and three
patients had return of circulation where circulatory arrest had been documented
for less than two minutes. Following WCRS, transient restoration of circulation
following circulatory arrest may occur, even following two minutes of circulatory
asystole, albeit rarely.
PMID- 29966115
TI - A clinical audit of an office-based anaesthesia service for dental procedures in
Victoria.
AB - There is an increasing number of specialties performing office-based procedures,
with many different providers practising in this field. Office Based Anaesthesia
Solutions is a private enterprise designed to be a high-quality general
anaesthesia and sedation service delivering care across 18 dental practices in
Victoria. We undertook a criterion-based audit of our practice standards and
outcomes. Following ethics approval, we retrospectively reviewed consecutive
patients managed by our service between March 2014 and July 2017. We collected
demographic data, information about anaesthesia technique, and surgical features.
We assessed our findings against the Australian and New Zealand College of
Anaesthetists (ANZCA) day surgery policy documents. During the specified period,
we provided anaesthesia or sedation for 1,323 patients. Their ages ranged from
two to 93 years (mean [standard deviation] 33.3 [18.6] years). Ninety-three
percent of patients were American Society of Anesthesiologists (ASA) physical
status classification 1 or 2. Patient demographics were in line with ANZCA day
surgical policy documents. Total intravenous anaesthesia was used in 1,054 of the
1,096 documented general anaesthesia cases. There were three unplanned hospital
transfers (annual incidence 0.07%). As this was the first Australian criteria
based audit of office-based anaesthesia (OBA) for dental procedures, we cannot
compare our findings directly to previous studies. However, we feel that our
patient demographics fell within acceptable ANZCA day procedure standards and our
adverse event rate was both very low and similar to other published international
adverse event rates. Our audit indicates that with careful screening processes,
patient selection and medical governance, OBA is a viable model of care for
patients undergoing dental procedures.
PMID- 29966116
TI - Survey of occupational fatigue in anaesthetists in Australia and New Zealand.
AB - Occupational fatigue in anaesthetists is recognised as a patient safety risk.
Better understanding of the issues surrounding their fatigue is needed. This
study aimed to ascertain the sources and effects of occupational fatigue amongst
anaesthetists in Australia and New Zealand. An anonymous online survey was sent
to 979 anaesthetists. The response rate was 38.0%. Most participants reported
regularly working over 40 hours per week; men reported five more hours per week
than women. Stated contributors to fatigue included long work hours, mental
strain at work, and personal and family demands. Fatigue-related behaviour was
reported more by men (OR [odds ratio]=2.6) and less by respondents reporting
eight or more hours of sleep before work (OR=0.6). Reporting at least one
instance of less than five hours off between shifts was predictive of falling
asleep while administering an anaesthetic (OR=1.6). More data are required to
support practices and policies that promote more time off between work periods
and increased time for sleep to reduce risk of fatigue.
PMID- 29966117
TI - Perioperative management of sodium-glucose cotransporter-2 inhibitors: importance
of a nuanced approach.
PMID- 29966118
TI - In reply.
PMID- 29966119
TI - Perioperative cessation of sodium-glucose cotransporter-2 inhibitors: 72 hours or
seven days?
PMID- 29966120
TI - In reply.
PMID- 29966121
TI - Assessing associations of fluid amount, type, and balance with acute kidney
injury after major surgery.
PMID- 29966122
TI - In reply.
PMID- 29966123
TI - Anaesthetic management of a patient with infection-induced acute encephalopathy 3
(IIAE3) who had previously developed an episode of severe encephalopathy
following a surgical procedure.
PMID- 29966124
TI - An alternative antiseptic solution to 5% povidone-iodine for regional ophthalmic
blocks in patients who are allergic to iodine.
PMID- 29966125
TI - Erratum.
PMID- 29966126
TI - H2 Receptor Antagonists versus Proton Pump Inhibitors in Patients on Dual
Antiplatelet Therapy for Coronary Artery Disease: A Systematic Review.
AB - OBJECTIVES: Mitigating the gastrointestinal (GI) bleeding risks of dual
antiplatelet therapy (DAPT) is a common clinical concern. While proton pump
inhibitors (PPIs) remain the most effective therapy, their adverse events warrant
considering alternatives, including Histamine 2 receptor antagonists (H2RAs).
METHODS: We searched for randomized controlled trials in MEDLINE, EMBASE, PubMed,
and Cochrane Central Register of Controlled Trials, published from 1980 to 2016.
After screening, 10 trials were eligible. We compared PPIs to H2RAs in patients
on DAPT in terms of 2 clinical and one laboratory outcomes; GI complications,
major adverse cardiovascular events (MACE) and high on-treatment platelet
reactivity (HTPR). Clinical and statistical inter-study heterogeneity was low for
all 3 outcomes (I2 = 0%, p > 0.05 for all). RESULTS: Fixed effects meta-analysis
suggested that PPIs were superior to H2RAs in preventing GI complications (OR
0.28, 95% CI 0.17-0.48) but with higher risk of HTPR (OR 1.28, 95% CI 1.030-1.60)
though without a higher incidence of MACE (OR 0.99, 95% CI 0.55-1.77).
CONCLUSIONS: PPIs are superior to H2RAs for gastroprotection in patients on DAPT.
However, PPIs are associated with HTPR, with no significant difference
demonstrated in MACE. Based on currently available data, the use of PPIs may be
warranted in selected patients on DAPT deemed at risk for GI complications.
PMID- 29966127
TI - Degenerated Keratinized Tumor Cells in Oropharyngeal Human Papilloma Virus
Associated Squamous Cell Carcinoma: A Pitfall in p16 Immunostaining of Fine
Needle Aspiration Specimens.
AB - OBJECTIVE: High-risk human papilloma virus (HPV) testing should be performed on
all patients with newly diagnosed oropharyngeal HPV-associated squamous cell
carcinoma (OPHPVSCC), and p16 immunostaining can be used as a surrogate marker.
Although in surgical pathology specimens p16 staining in > 70% of the tumor cells
is considered a positive result, the interpretation in fine-needle aspiration
(FNA) specimens has remained controversial. STUDY DESIGN: FNA of neck lymph nodes
and corresponding surgical specimens from 42 patients with OPHPVSCC were
reviewed. RESULTS: In FNA specimens, 38 cases (90.5%) had viable tumor cells, 32
(76.2%) had keratin debris, and 36 (85.7%) had degenerated keratinized tumor
cells. Twenty-seven of 27 (100%) had positive p16 staining in > 70% of viable
tumor cells, while the degenerated tumor cells were negative. Twenty of 24
(83.3%) primary OPHPVSCC exhibited focal degenerated keratinized tumor cells
and/or keratin debris. CONCLUSIONS: This study showed that the majority of the
OPHPVSCC metastases in lymph nodes had degenerated keratinized tumor cells and
keratin debris. Many primary OPHPVSCC also demonstrated focal keratinization
and/or degeneration. The degenerated tumor cells showed no immunoreactivity to
p16. The same 70% cutoff used in histologic specimens should be applied in
cytologic specimens, but only the viable tumor cells should be counted.
PMID- 29966128
TI - Does Caffeine Consumption Increase the Risk of New-Onset Atrial Fibrillation?
AB - OBJECTIVE: Caffeine has been considered a trigger for atrial fibrillation (AF).
We conducted a meta-analysis including a dose-response analysis to assess the
relationship between caffeine consumed and incidence of AF. METHODS: Data from
selected studies represented 176,675 subjects (AF in 9,987 [5.7%]). Caffeine
content varied widely, ranging from 40 to 180 mg per cup of coffee. For purposes
of the calculations in this study, we assumed 140 mg of caffeine in a standard 12
oz cup of coffee. RESULTS: No significant difference was found in AF incidence
when the subjects consuming less than 2 cups of coffee per day were compared to
subjects with higher consumption, 1.068 (0.937-1.216). The risk of AF was higher
among subjects consuming less than 2 cups of coffee daily when compared to higher
daily consumption subjects. A lower incidence of AF was found among people
consuming more than 436 mg daily. CONCLUSION: The incidence of AF is not
increased by coffee consumption. In fact, we found a lower incidence of AF when
caffeine consumption exceeded 436 mg/day. Therefore, based on available evidence
there is no association between caffeine intake and AF risk.
PMID- 29966129
TI - Nasalisation in the Production of Iraqi Arabic Pharyngeals.
AB - AIM: This paper presents the auditory and acoustic investigations of pharyngeal
consonants in Iraqi Arabic (IA). While the contested place and manner of
articulation of these sounds have been the subject of investigation in many
studies, the focus here is novel: we set out to investigate the extent to which
pharyngeals in IA are accompanied by auditory nasalisation and how widespread the
effect is across oral and nasal contexts. METHODS: Auditory and acoustic
properties of nasalization, as produced by nine male speakers of IA, were
investigated in target words with oral, nasal, and pharyngeal environments.
RESULTS: When combined with oral consonants, pharyngeals exhibit little or no
nasalisation; however, when pharyngeal are combined with nasals, they exhibit
various degrees of nasalisation, sometimes beyond what is found for a nasal
environment alone. This is especially so for voiced pharyngeals, which display
more nasalisation than their voiceless counterparts. A principle component
analysis combining all the acoustic correlates examined demonstrates a definite
contribution of pharyngeals to the presence of nasalisation. CONCLUSION: The
epilaryngeal constriction and variability in the articulation of pharyngeals are
thought to be responsible for the nasalisation effect and may act as potential
drivers for sound change in IA pharyngeals.
PMID- 29966131
TI - Does Aortic Angulation Impact Outcomes in TAVR.
PMID- 29966132
TI - Proton Pump Inhibitors and Dual Antiplatelet Therapy: Is the Story Over?
PMID- 29966130
TI - The Viennese EDDY Study as a Role Model for Obesity: Prevention by Means of
Nutritional and Lifestyle Interventions.
AB - OBJECTIVES: Obesity in children and adolescents is a worldwide dramatic health
problem, for which treatment is mostly unsuccessful. Therefore, prevention is the
most important measure to tackle this problem. The 'EDDY' study as an
interventional cohort study with a 1-year lifestyle intervention aimed to affect
the lifestyle and nutrition habits of adolescents by intervention with
nutritional training and sports programs to prevent obesity. METHODS: Four
Viennese schools were cluster-randomized into an intervention group and a control
group. A total of 141 pupils aged 11-14 years were included. The intervention
group received a comprehensive, age-appropriate training on nutrition and
lifestyle exercise intervention for 12 months. Before and after intervention and
at two follow-ups, subjects were anthropometrically measured. In addition,
knowledge of nutritional issues and eating habits were measured with
questionnaires. RESULTS: The data imply an improvement of nutrition knowledge, a
significant reduction in the consumption of junk food (p = 0.01), sweets (p =
0.001) and salty snacks (p < 0.001) as well as a slight improvement of physical
performance after intervention. Although there was a trend for a less increase of
body fat in the intervention group, no significant changes could have been shown
in the anthropometric data. CONCLUSIONS: An age-adjusted lifestyle intervention
based on dietary training and exercise can improve the nutritional knowledge and
eating habits of school children.
PMID- 29966133
TI - Association between Polymorphisms of the DRD2 and ANKK1 Genes and Suicide
Attempt: A Preliminary Case-Control Study in a Mexican Population.
AB - BACKGROUND: The aim of this study was to analyze the possible association of
polymorphic variants of the DRD2 and ANKK1 genes with suicide attempt in a
Mexican population. METHODS: We conducted a case-control study in 289 subjects
(166 suicide attempters and 123 healthy controls). We genotyped 2 polymorphisms
of DRD2 (rs6275 and rs1799978) and 1 polymorphism of ANKK1 (rs1800497); then we
analyzed the association between suicide attempt and these polymorphisms through
genotypes, alleles, and inheritance models. RESULTS: Individuals who carried the
TT genotype of the rs1800497 showed a 3-fold risk of attempting suicide (OR =
3.01; 95% CI 1.56-5.81, p = 0.001) when evaluated through the recessive model. In
an analysis stratified by gender, this risk factor remained present among females
(OR = 2.81; 95% CI 1.37-5.75) as well as males (OR = 3.3; 95% CI 1.01-10.77).
CONCLUSION: Our results suggest that the rs1800497 variant of the ANKK1 gene
could increase the risk of suicide attempt in a Mexican population. However,
further studies using larger samples are necessary to obtain more conclusive
results.
PMID- 29966134
TI - Understanding the Blind Spots of Psychosis: A Wittgensteinian and First-Person
Approach.
AB - BACKGROUND: Experiences of psychosis are often assumed to be strange, bizarre, or
incomprehensible. The aim of this article is to offer a new step towards a better
understanding of how the psychotic process affects a prereflective background.
METHODS: We use concepts from the philosophy of Ludwig Wittgenstein to clarify
the first-person perspective on psychosis of one of the authors. RESULTS: We
describe the early psychotic process as breaking down the "nest of propositions,"
shaking the scaffolds of our language games. Hereby, the prereflective background
that forms our existential orientation in the world is fundamentally altered. We
identify different aspects of this process: a dialectic of aha and anti-aha
experiences, the experience of groundlessness, and blind spots. Acknowledging and
exploring the depth and impact of this process on a person's world may be a first
step towards resolving their isolation and suffering. Philosophy can facilitate
such an exploration, while interpersonal activation may offer structure and trust
in the world, helping the patient to find solid ground in action and interaction.
CONCLUSION: This article combines a philosophical approach with a first-person
perspective on psychosis to illuminate aspects of psychosis that have not been
described or elaborated on before. We argue that psychosis entails an experience
of existential groundlessness. Our view has implications for treatment of and
recovery from psychosis.
PMID- 29966137
TI - Abstract Service.
PMID- 29966135
TI - Novel ABCD1 Gene Mutation in Adrenomyeloneuropathy with Hypoplasia and Agenesis
of the Corpus Callosum.
AB - BACKGROUND: Adult adrenomyeloneuropathy (AMN) is caused by mutations in the ABCD1
gene. Some pure AMN patients develop cerebral demyelination late in life.
However, hypoplasia and agenesis of the corpus callosum (CC) has never been
reported in AMN patients. OBJECTIVE: To describe a new clinical variant of AMN
that is possibly caused by a novel ABCD1 gene mutation. METHODS: A total of 10
members in an X-linked inherited family were examined. The age at onset,
progression of disability, and clinical manifestations were collected. Blood
tests of the index case were conducted in an academic hospital. Cerebral and
spinal MRI was performed in 4 affected members using a Siemens 3.0-T or Hitachi
1.0-T MR scanner. Whole-exome sequencing was conducted in the index case, which
was subsequently validated by Sanger sequencing in the family. RESULTS: The
patients displayed typical degenerative spastic paraparesis and peripheral
sensorimotor neuropathy with some intrafamilial variations. In addition to
neurological deficits, all male patients displayed alopecia since adolescence.
Furthermore, an increase in plasma long-chain fatty acids was observed. Based on
these presentations, adult AMN was diagnosed for the patients. Intriguingly,
cerebral MRI showed multiple types of hypoplasia and agenesis of the CC including
anterior remnant CC agenesis, truncated corpus and splenium, anterior remnant CC
agenesis along with thin corpus and splenium. Whole-exome sequencing revealed a
nonsense mutation (c.231G>A) which results in a truncated protein product
(p.W77X) that might be nonfunctional. No other mutations associated with alopecia
or hypoplasia and agenesis of the CC were identified in the exome-sequencing
database. CONCLUSION: In addition to the typical symptoms such as spastic
myelopathy, cognitive impairment, mixed neuropathy, and alopecia, AMN patients
can also display hypoplasia and agenesis of the CC, which was not described in
the other AMN patients reported before.
PMID- 29966138
TI - Meetings and Conferences * Tagungen und Kongresse.
PMID- 29966139
TI - Retracted: Effect of Cinnamaldehyde on Glucose Metabolism and Vessel Function.
AB - This paper was retracted on the authors' request due to duplicate publication.
This experiment was entrusted to a third party called Nanjing Changcong Biology
Company, and we found that some of the data reported in the Results figures were
duplicated in another published paper. The pdf file of the above-mentioned paper
is available from the Editorial Office on request.
PMID- 29966140
TI - Vertebral Arteriovenous Fistula: A Rare Complication Following Transpedicular
Occipitocervical Fixation in a Patient with Atlantoaxial Dislocation.
AB - Vertebral arteriovenous fistula (AVF), a complication of a vertebral artery
injury (VAI), is a rare but serious complication of upper cervical spine fixation
surgery. We report a case of a 59-year-old female patient who had a vertebral AVF
following transpedicular occipitocervical fixation surgery. Endovascular
embolization of the AVF was successfully performed using ethylene vinyl alcohol.
From this case we learned that preoperative evaluation of the course of the
vertebral artery is necessary, and vertebral artery embolism is an effective and
safe method to treat vertebral AVF after proof of a patent second vertebral
artery.
PMID- 29966141
TI - Ultrasonography for the Diagnosis of Carpal Tunnel Syndrome in Diabetic Patients:
Missing the Mark?
AB - PURPOSE: Diabetes mellitus (DM) and carpal tunnel syndrome (CTS) are common
pathologies. The diagnosis of CTS can be facilitated by the use of an ultrasound
based wrist-to-forearm ratio (WFR) of the nerve diameter. However, the
applicability of WFR in DM-patients is not yet clear. MATERIALS AND METHODS: 233
wrists of 153 patients were examined. Cross-sectional areas (CSA) of the median
nerve were obtained using a linear array probe. The WFR was calculated. RESULTS:
Diabetics with CTS had significantly lower WFR values than non-diabetics with CTS
(p = 0.002). There was no difference between the WFR of diabetics with and
without CTS (p = 0.06). The diagnostic accuracy between diabetics with and
without CTS was low for measurements of WFR (ROC AUC = 0.630, 95 % CI 0.541 -
0.715, p = 0.011). CONCLUSION: Our findings suggest that the WFR has a low
diagnostic accuracy in diabetic patients with CTS and should be used with caution
in those patients. KEY POINTS: . The diagnostic accuracy of WFR is low in
patients with DM. . WFR should not be used in patients with DM. . The sonographic
evaluation of the median nerve in patients with DM should focus on morphological
changes. CITATION FORMAT: . Steinkohl F, Loizides A, Gruber L et al.
Ultrasonography for the Diagnosis of Carpal Tunnel Syndrome in Diabetic Patients:
Missing the Mark?. Fortschr Rontgenstr 2018; DOI: 10.1055/a-0639-5713.
PMID- 29966142
TI - Evaluation of Myocardial Damage After Electroconvulsive Therapy: Analyses of High
Sensitive Cardiac Troponin I and N-Terminal pro-B-type Natriuretic Peptide.
AB - Electroconvulsive therapy (ECT) is a remarkably safe procedure. However, there
might exist a subgroup of patients with an increased risk for cardiovascular
events. The cardiac-specific enzymes high-sensitive cardiac troponin I (hscTnI)
and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured before
and after ECT in 23 patients. No relevant increase of hscTnI after ECT was found.
Mean NT-proBNP levels were higher after ECT and in three patients a new NT-proBNP
elevation after ECT was identified. In conclusion, our small study did not find
any evidence for myocardial damage due to ECT by measuring hsTnI, but an increase
of NT-proBNP, whose clinical relevance could only be speculated, yet.
PMID- 29966143
TI - Dilation catheter-guided mini-forceps biopsy improves the diagnostic accuracy of
malignant biliary strictures.
AB - BACKGROUND: Tissue sampling for biliary stricture is important for differential
diagnosis and further treatment. The aim of this study was to assess a novel
dilation catheter-guided mini-forceps biopsy (DCMB) method in the diagnosis of
malignant biliary strictures. METHODS: 42 patients with malignant biliary
stricture who underwent both brush cytology and DCMB during endoscopic retrograde
cholangiopancreatography between October 2014 and November 2015 were
retrospectively included. During DCMB, the mini biopsy forceps was introduced
into the biliary stricture through the dilation catheter, and then the position
and direction of the forceps were adjusted to obtain tissue samples. RESULTS:
The positive rate of DCMB was significantly higher than that of brush cytology
(81.0 % [34/42] vs. 38.1 % [16/42]; P < 0.001). No severe complications occurred;
three patients (7.1 %) experienced mild procedure-related acute pancreatitis.
CONCLUSIONS: The novel DCMB technique was a practical, safe, efficient, and low
costing method for diagnosing malignant biliary stricture with a high accuracy
rate.
PMID- 29966144
TI - [Who Benefits in Graded Return to Work on Behalf of the German Pension Insurance?
Results of a Cohort Study].
AB - BACKGROUND: In view of growing numbers and large expenditures Graded Return to
work (GRTW) gained in importance for the German Pension insurance in the last
decade. Therefore, the questions were whether GRTW is effective in the German
rehabilitation system and if there are any criteria for or against the assignment
to GRTW following medical rehabilitation. METHODS: In a large cohort study 40,262
persons were asked to fill out questionnaires at the start of and 15 months after
medical rehabilitation. The control group consisted of persons without GRTW after
rehabilitation. Propensity Score Matching was used to balance the groups. Primary
outcomes were the rate of employment, the rate of invalidity pension k and the
time of sick leave in the follow-up. The role function of the SF-36 and mental
health (PHQ-4) were defined as secondary outcomes. RESULTS: The matching resulted
in 1,009 pairs. The GRTW group had a higher rate of return to work, a lower rate
of disability pensions and less weeks of sick leave in the follow-up. Moreover, a
higher role function and mental health was observed in the intervention group.
The effects were particularly pronounced for patients with a high initial risk of
permanent disability as well as higher sick leave prior rehabilitation.
CONCLUSION: Following these results there is a clear evidence for the
effectiveness of GRTW following medical rehabilitation. GRTW is indicated for
persons with prior sick leave of more than 3 months or a high risk of permanent
disability (>8 points on the SIBAR scale, Screening Instrument for the Assessment
of Need for Occupation Related Treatment in Medical Rehabilitation). For persons
with only few weeks of sick leave or at most 5 points on the SIBAR scale there is
a clear contraindication.
PMID- 29966145
TI - [Rehabilitation Program for Persons with Relatives Suffering from Dementia:
Results of a Longitudinal Observational Study].
AB - BACKGROUND: Caregiving relatives of dementia patients are exposed to considerable
burdens. A multimodal rehabilitation concept which enables the inpatient
treatment of caregiving relatives together with the dementia patients was
evaluated. METHODS: Questionnaire survey including 121 caring relatives at 3
times of measurement. Indicators of subjective health and the use of nursing and
psychosocial support services were measured during the course of the study.
RESULTS: Relevant improvements in health can be seen after rehabilitation. Six
months after rehabilitation, the effects decrease, but do not reach the baseline
value before rehabilitation for any of the variables measured. CONCLUSION: The
multimodal rehabilitation concept shows sustainable effects, at least in some
variables. In connection with the high level of satisfaction of the participants,
the results indicate that the rehabilitation concept is successful and is
associated with a large health benefit.
PMID- 29966146
TI - [Work-related Functional Capacity Evaluation with the Sapphire System(r):
Assessment of Consistency and Pain Behavior in the Context of Employment Status].
AB - OBJECTIVE: The study investigates pain behaviour and consistency of results in
the framework of work-related functional capacity evaluation with the FCE
assessment system Sapphire(r). METHODS: We included 129 inpatients from
orthopaedic rehabilitation. The subjects were subdivided into 4 groups according
to their Sapphire test results: (1) overt pain behaviour, no test inconsistency,
(2) lack of consistency, no pain-related self-limitation, (3) overt pain
behaviour with test inconsistency (complex peculiarities) and (4) no
peculiarities in pain behaviour or in test consistency (reference group).
Multinomial logistic regression analysis was performed to estimate the
associations with potential predictors of these peculiarities. RESULTS:
Disability claim was strongly associated with biased test results co-occurring
with overt pain behaviour. In contrast, no associations were observed between
disability claim and isolated appearance of pain behaviour. CONCLUSION:
Assessments of consistency and pain behaviour are helpful for detecting biased
test results and maladaptive coping with pain. Further research to clarify the
role of maladaptive coping with pain and motivational deficits can be advocated.
PMID- 29966147
TI - [Rehabilitation of Patients with Peripheral Arterial Disease in the Context of
Guideline Recommendations].
AB - BACKGROUND: The study examines the rehabilitation of patients with peripheral
arterial disease (PAD) in the context of current guidelines. METHODOLOGY: All
medical rehabilitations completed in 2014 with the initial diagnosis of PAD (ICD
10-GM: I70.2) were analyzed. Sociodemographic and socio-medical characteristics
as well as the therapies received were evaluated and compared to current
guideline recommendations. RESULTS: 1289 patients with PAD (mean age 56.1 years,
78.3% men) where included in the study. Social-medical parameters outline a
fairly multimorbid cohort with poor prognosis for long-term occupational outcome
and survival. Evidence-based therapies based on guideline recommendations
(including supervised walking 58%, vascular training 63% and PAD-specific
education lessons 64%) were performed to a lesser extent than expected.
CONCLUSION: The results suggest an overall high standard of rehabilitation of
patients with PAD. However, the poor socio-medical prognosis and the partial lack
of compliance with guideline recommendations indicate the need for action. The
development of specific recommendations for rehabilitation of PAD-patients could
therefore be useful.
PMID- 29966148
TI - [Social Work in Medical Rehabilitation - A Review of Current Research].
AB - BACKGROUND: Quality assurance approaches by the German Statutory Pension
Insurance emphasized the need of evidence-based practice for social work in
medical rehabilitation. This study aims to show the state of research in
rehabilitation science concerning social work and its effectiveness. METHODOLOGY:
The review is based on a literature search in 3 databases (Pubmed, Web of
Sciences, Scopus) and a hand search in rehabilitation science journals and
proceedings. RESULTS: 52 of 176 articles from 2000 to 2016 met the inclusion
criteria. Social work is a common service in routine clinical practice with a
substantial variation on the institutional level and between indications.
Analysis of quality assurance data and observational studies showed negative as
well as positive effects. CONCLUSIONS: The results indicate the need of an
evidence-based practice of social work in medical rehabilitation.
PMID- 29966149
TI - Effects of Concomitant Administration of a Dipeptidyl Peptidase-4 Inhibitor in
Japanese Patients with Type 2 Diabetes Showing Relatively Good Glycemic Control
Under Treatment with a Sodium Glucose Co-Transporter 2 Inhibitor.
AB - We conducted this study to determine whether additional administration of a
dipeptidyl peptidase-4 (DPP-4) inhibitor might provide further improvement of the
glycemic control in Japanese type 2 diabetes patients showing relatively good
glycemic control under treatment with a sodium glucose co-transporter 2 (SGLT2)
inhibitor. Five SGLT2 inhibitor (luseogliflozin, dapagliflozin, tofogliflozin,
empagliflozin and canagliflozin) preparations and five DPP-4 inhibitor
(sitagliptin, vildagliptin, alogliptin, anagliptin and linagliptin) preparations
were used. The results showed that monotherapy with SGLT2 inhibitor produced
significant decreases of the body weight and BMI, hemoglobin A1c (HbA1c) also
decreased, but not to a significant extent. However, decreases of the serum
aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma
glutamyltransferase (gamma-GTP) and uric acid were observed in this group. On the
other hand, in type 2 diabetes patients treated concomitantly with a DPP-4
inhibitor and SGLT2 inhibitor, significant decrease of the HbA1c was observed,
indicating the favorable effect of the concomitant therapy. The body weight and
BMI decreased. As for the serum lipid profile, elevation of the serum HDL
cholesterol (HDL-C) was observed. Furthermore, AST, ALT, gamma-GTP and uric acid
decreased in the combined treatment group. Then, the therapeutic responses to
concurrent administration with SGLT2 inhibitor of each of the 5 individual DPP-4
inhibitors used in this study were analyzed. The results showed that concomitant
administration of sitagliptin, a DPP-4 inhibitor, with the SGLT2 inhibitor
yielded the best results in terms of the lowering of the HbA1c and improvement of
the serum lipid profile.
PMID- 29966150
TI - Effects of Concomitant Administration of Sodium Glucose Co-transporter 2
Inhibitor with Insulin on Hemoglobin A1c, Body Mass Index and Serum Lipid Profile
in Japanese Type 2 Diabetic Patients.
AB - In patients with type 2 diabetes mellitus who show suboptimal blood glucose
control under insulin therapy alone, concomitant treatment with an additional
hypoglycemic agent that differs in its mechanism of action from insulin may be
considered. We conducted this clinical trial to explore whether further control
of increased blood glucose level can be achieved with concomitant use of sodium
glucose co-transporter 2 (SGLT2) inhibitor as concomitant with other hypoglycemic
therapy, as compared to SGLT2 inhibitor monotherapy, in patients with type 2
diabetes mellitus showing decrease in blood glucose level but less than the
effect of insulin monotherapy and there was no significant differences. In the
SGLT2 inhibitor monotherapy group, decreases of the serum hemoglobin A1c (HbA1c)
level, body weight, body mass index (BMI) and serum triglyceride, and elevation
of the serum high density lipoprotein cholesterol concentration were observed as
compared to the baseline values. In the type 2 diabetic patients under insulin
therapy who received combined insulin plus SGLT2 inhibitor therapy, however
decreases in the body weight and BMI, with only a tendency towards decrease of
the serum HbA1c value, not reaching statistical significance, were observed. The
combined therapy group also showed no appreciable changes of the serum
triglyceride level, while the serum adiponectin level increased. The present
study data indicate that combined insulin plus SGLT2 inhibitor treatment failed
to afford any further improvement of the blood glucose control, as compared to
SGLT2 monotherapy, in Japanese type 2 diabetic patients.
PMID- 29966151
TI - Preparation and Properties of 5-Fluorouracil-Loaded Chitosan Microspheres for the
Intranasal Administration.
AB - OBJECTIVE: To study the preparation technique of 5-fluorouracil and the release
characteristic of 5-fluorouracil-loaded chitosan microspheres for the intranasal
administration. METHODS: 5-fluorouracil-loaded chitosan microspheres were
prepared by emulsion chemical cross-link technique. The orthogonal experimental
design was used to optimize the preparation procedure. Dynamic dialysis method
was applied to determine the release characteristic of microspheres in vitro and
its influencing factors. Swelling behavior was expressed by swelling ratio. The
degree of mucoadhesion was investigated by determining the mucociliary transport
rate(MTR) of the microparticle across a frog palate. RESULTS: Microspheres with a
good shape and narrow size distribution were prepared. The average diameter was
43+/-4 MUm. The drug loading was (38.5+/-1.0) %. The entrapment efficiency was
(79.0+/-1.8) %. The drug release profile in vitro could be described by Higuichi
eqution as Q=0.1035t1/2+0.0284 (r=0.9965). Chitosan had good mucoadhesive
property and caused a significant reduction in MTR(P<0.01). CONCLUSION: The
optimized technique has a good reproducibility and a high entrapment efficiency,
so it could be used to prepare 5-fluorouracil-loaded chitosan microspheres for
the intranasal administration.Chitosan is a good material for nasal preparation
and has prospective development in the pharmaceutical field.
PMID- 29966152
TI - Expenditures Of Metabolic Diseases - An Estimation on National Health Care
Expenditures of Diabetes and Obesity, Hungary 2013.
AB - BACKGROUND: Obesity could be considered as the main consequence of unhealthy
nutrition, responsible for many pathological alterations in human. Obese patients
usually need more health care services. The aim of the study was to estimate the
financial expenditures of health care provisions in Hungary, related to obesity
and diabetes, as its main pathological consequence. METHODS: Data of the
Hungarian National Health Insurance Fund (NHIF) were collected for 2013,
regarding finances of secondary care, hospital services, reimbursement for
medications and healing aids of diabetic patients together with selected
morbidities linked to obesity, based on the codes of the International
Classification of Diseases (ICD) and calculated their population prevalence on
the population-attributable fraction (PAF). RESULTS: Financial data regarding
diabetes care resulted in a 40,311 Million HUF (129 Million EUR) national fund
expenses, beside a 7,173 Million HUF (23 Million EUR) contribution from patients.
Estimated total health care expenditures related to obesity were 58,986 Million
HUF (188 Million EUR) and the financial contribution of patients was calculated
as 25,316 Million HUF (81 Million EUR). These data represent a 5.2% and 9.3% of
the whole national health services, 16% and 30% of the whole drug-reimbursement
budgets, respectively. CONCLUSIONS: Although expenditures for some obesity
related pathologies analyzed in this paper represent 0.28% of the national GDP,
considering other morbidities and other patient's expenses, the real ratio could
be between 0.5-1%. The increasing number of overweight and obese persons requires
more focus in public health, higher awareness in the society and more
governmental support.
PMID- 29966153
TI - Neuro-Endocrine Recovery After Pituitary Apoplexy: Prolactin as a Predictive
Factor.
AB - OBJECTIVE: Pituitary apoplexy is a serious medical complication of a pre-existing
pituitary adenoma characterized by a variety of clinical symptoms ranging from
mild headache to neurologically impaired and finally comatose patients.
Management options are surgery or conservative treatment (e. g., with
dexamethasone). Surgery is commonly performed in case of severe acute
neurological and visual symptoms. However, prospective studies demonstrating a
benefit of surgery over conservative treatment in terms of visual, neurological
and even endocrine outcomes are lacking. Decision making is still controversial,
and recommendations for surgery are based on low evidence grades and focus on
visual impairment. Endocrine function and especially markers identifying patients
with potential for pituitary recovery after surgery are not well described in the
literature. PATIENTS AND DESIGN: We analysed data from 24 patients (m:f/16:8)
with a median age of 64 yrs (38 to 83yrs) that underwent surgery for pituitary
apoplexy regardless of time from symptom onset. Apoplexies were necrotic in 14
cases and haemorrhagic in 10 cases. RESULTS: Preoperatively, 7 patients (29.2%)
showed complete anterior pituitary insufficiency, 16 patients (66.6%) had partial
anterior pituitary insufficiency and one patient (4.17%) had normal pituitary
functions. Persistent panhypopituitarism was found in 7 patients (29.2%), whereas
an overall improvement of pituitary function was noted in 13 (57.1%) patients.
Preoperative prolactin (PRL) levels were significantly associated with recovery
of endocrine functions, whereas specifically all patients with preoperative PRL
levels of at least 8.8 ng/ml recovered partially or fully. Time to surgery (0-7
days vs. 1-4 weeks vs.>4 weeks) was not significantly associated with outcome.
CONCLUSIONS: Our data emphasize that normal and high preoperative PRL levels are
associated with better endocrine outcome after surgery. We conclude that patients
benefit from surgical intervention even after delayed diagnosis with the serum
PRL levels is being a valid biomarker for clinical decision making.
PMID- 29966154
TI - Thyroid Peroxidase Antibody is Associated with Plasma Homocysteine Levels in
Patients with Graves' Disease.
AB - PURPOSE: Homocysteine is associated with cardiovascular, inflammation and
autoimmune diseases. Previous studies have shown that thyroid peroxidase antibody
is associated with homocysteine levels in hypothyroidism. The relationship
between thyroid antibodies and homocysteine in hyperthyroidism remains unclear.
In this study, we aimed to investigate the association of thyroid antibodies with
homocysteine in patients with Graves' disease. METHODS: This was a cross
sectional study including 478 Graves' disease patients who were consecutively
admitted and underwent radioiodine therapy. Homocysteine, thyroid hormones,
thyroid antibodies, glucose and lipids were measured. RESULTS: Patients with
homocysteine levels above the median were older and had unfavorable metabolic
parameters compared to patients with homocysteine levels below the median.
Thyroglobulin antibody or thyroid peroxidase antibody was associated with
homocysteine levels (beta=0.56, 95%CI 0.03-1.08, p=0.04; beta=0.75, 95%CI 0.23
1.27, p=0.005). The relationship between thyroid peroxidase antibody and
homocysteine remained significant when additionally adjusting for free
triiodothyronine (beta=0.76, 95%CI 0.24-1.28, p=0.004). The presence of a
homocysteine level above the median increased significantly with increasing
thyroid peroxidase antibody quartiles in the logistic regression (OR=1.74, 95%CI
1.27-2.39, P for trend=0.001). Homocysteine levels increased significantly with
increasing thyroid peroxidase antibody quartiles (p=0.005). Thyroid peroxidase
antibody had no significant effect on other traditional cardiovascular risk
factors. CONCLUSIONS: Thyroid peroxidase antibody is independently and positively
associated with homocysteine levels in patients with Graves' disease. Thyroid
peroxidase antibody may be associated with the cardiovascular risk of patients
with Graves' disease through its effect on homocysteine.
PMID- 29966155
TI - Rehabilitation in Germany 2004-2016 A Multicenter Analysis Over a Period of 13
Years in Children and Adolescents with Diabetes Mellitus.
AB - : In the treatment of children/adolescents with diabetes medical rehabilitation
plays an important role. It was the aim of the survey to analyze trends in the
number of patients admitted to rehabilitation, the quality of diabetes care, the
incidence of acute complications, risk factors for cardiovascular co-morbidities
like lipids and blood pressure and the familial status nationwide and over a
period of 13 years. METHODS: Currently seven hospitals offer in-patient
rehabilitation for children/adolescents with diabetes in Germany. Six hospitals
participated in the survey. All children/adolescents (n=7.163) who participated
in an in-patient rehabilitation 01/01/2004-31/12/2016 were included.
Clinical/familial data were assessed: age, sex, family situation, type/duration
of diabetes, insulin dosage, self-monitoring, acute complications, height, body
weight, blood pressure and laboratory parameters. For collecting and storage of
data the computer software DPV(r) (Diabetes-Patienten-Verlaufsdokumentation,
University of Ulm, Germany) was used. Statistical analyses were performed using
the programme SAS (Statistical Analysis Software 9.4, SAS Institute Inc, Cary,
North Carolina, USA). RESULTS: During the study period 7.163 patients took part
in 10.987 in-patient rehabilitation procedures. The yearly number of patients
participating in rehabilitation remained stable. There was no change in the
quality of diabetes control (HbA1c: p=0.30, fasting blood glucose: p=0.80). The
incidence of severe hypoglycaemia decreased (p<0.001). The incidence of
ketacidosis remained stable (p=0.18). The frequency of blood glucose self
monitoring increased (p<0.001). The same was true for patients treated with CSII
(p<0.001), whereas the numbers of patients treated with CT or ICT decreased (both
p<0.001). There was no change in patients' total insulin dose (p=0.01). There was
a decrease of the number of patients living with both parents (p<0.001), the
percentage of children/adolescents living with mother or father alone increased
(p<0.001). The percentage of children/adolescents living in mixed cultural
families or having a background of immigration increased (p<0.001). CONCLUSIONS:
There is a change in medical rehabilitation: The number is stable, the proportion
of patients using CSII increased, the number of patients living with single
parents and the percentage of patients from culturally mixed families increased
also.
PMID- 29966157
TI - ?
PMID- 29966158
TI - ?
PMID- 29966156
TI - Iterative Model Reconstruction (IMR) in MDCT Below 2 mSv for the Detection of
Urinary Calculi: Diagnostic Accuracy and Image Quality in Comparison to Filtered
Back-Projection and 4th Generation Iterative Reconstruction (iDose4).
AB - PURPOSE: The purpose of the study was to assess the impact of iterative model
reconstruction (IMR) on reader confidence with respect to stone detection and
image quality in comparison to filtered back-projection (FBP) and iDose level 4
(iDose4) in abdominal MDCT with radiation doses below 2 mSv. MATERIALS AND
METHODS: For 32 consecutive patients with suspected ureteral stone disease, the
raw data of unenhanced 256 slice MDCT (120 kV, 40 reference mAs, mean CTDIvol:
2.7 +/- 0.8 mGy, mean DLP: 126 +/- 38 mGy * cm) were reconstructed using a
prototype version of IMR (levels 1 - 3), iDose4 (level 4) and FBP at a 3 mm slice
thickness. Image analysis was independently performed by two radiologists in a
blinded fashion. The reader confidence level with respect to stone detection was
recorded based on a 5-point scale (1 - certain exclusion; 5 - concrement
definitely present) as well as for the evaluation of image quality regarding the
depiction of anatomical details (1 - poor; 5 - excellent). A clinical reference
standard for stone detection was not established. Statistical evaluation included
weighted kappa analysis and Wilcoxon test. RESULTS: 17 pelvic and ureteral stones
were found. 11 further concrements were located within the ostium of the urinary
bladder or the bladder itself. Applying IMR, a distinct improvement in image
quality was observed at every level (mean value for FBP, 2.0; iDose4, 2.9; IMR
L1, 4.2; IMR L2, 4.0; IMR L3, 3.9; all p < 0.001). Applying the higher IMR levels
L2 and L3, a certain level of so-called "blotchiness" of anatomical contours was
observed. Reader confidence was significantly improved and was independent of IMR
level (certain stone detection FBP, 69 %; iDose4, 81 %; IMR L1 to L3, 95 %; all p
> 0.001). With increasing IMR levels, the reduction in streak artifacts was
quantified by a decrease in image noise. A loss of anatomical information was not
observed. The sensitivity rates for stone detection were equivalent for all MDCTs
reconstructed with FBP, iDose4 and IMR. A mean effective dose of 1.9 +/- 0.6 mSv
was calculated. CONCLUSION: In comparison to FBP and iDose4, a significant
increase in mean image quality, reduction in image noise and improvement in
subjective reader confidence can be achieved by applying IMR even at
significantly reduced dose settings below 2 mSv. Results indicate that a further
dose reduction might be possible with IMR. KEY POINTS: . Urinary tract. .
urolithiasis. . iterative reconstruction. CITATION FORMAT: . Schmidt-Holtz J,
Laqmani A, Butscheidt S et al. Iterative Model Reconstruction (IMR) in MDCT Below
2mSv for the Detection of Urinary Calculi: Diagnostic Accuracy and Image Quality
in Comparison to Filtered Back-Projection and 4th Generation Iterative
Reconstruction (iDose4). Fortschr Rontgenstr 2018; 190: 630 - 636.
PMID- 29966159
TI - ?
PMID- 29966160
TI - ?
PMID- 29966161
TI - ?
PMID- 29966162
TI - ?
PMID- 29966163
TI - ?
PMID- 29966164
TI - Use of NOACs in the Peri-Operative Management of Patients with Atrial
Fibrillation: To Stop, Bridge or Continue?
PMID- 29966165
TI - FVIII, Protein C and the Risk of Arterial Thrombosis: More than the Sum of Its
Parts.
PMID- 29966166
TI - Presence of Varicose Veins is the Most Important Risk Factor for Developing PTS.
PMID- 29966167
TI - Venous Thromboembolism (VTE) Incidence and VTE-Associated Survival among Olmsted
County Residents of Local Nursing Homes.
AB - Nursing home (NH) residency is an independent risk factor for venous
thromboembolism (VTE), but the VTE burden within the NH population is uncertain.
This study estimates VTE incidence and VTE-associated mortality among NH
residents. We identified all NH residents in any NH in Olmsted County, Minnesota,
United States, 1 October 1998 to 31 December 2005 and all first lifetime VTE
among county residents to estimate VTE incidence while resident of local NHs
(NHVTE), using Centers for Medicare and Medicaid Services Minimum Data Set and
Rochester Epidemiology Project resources. We tested associations between NHVTE
and age, sex and time since each NH admission using Poisson modelling.
Additionally, we tested incident NHVTE as a potential predictor of survival using
Cox proportional hazards, adjusting for age, sex and NH residency. Between 1
October 1998 and 31 December 2005, 3,465 Olmsted County residents with >=1
admission to a local NH, contributed 4,762 NH stays. Of the 3,465 NH residents,
111 experienced incident NHVTE (2.3% of all eligible stays), for an overall rate
of 3,653/100,000 NH person-years (NH-PY). VTE incidence was inversely associated
with time since each NH admission, and was highest in the first 7 days after each
NH admission (18,764/100,000 NH-PY). The adjusted hazard of death for incident
NHVTE was 1.90 (95% confidence interval [CI]: 1.38-2.62). In conclusion, VTE
incidence among NH residents was nearly 30-fold higher than published incidence
rates for the general Olmsted County population. VTE incidence was highest within
7 days after NH admission, and NHVTE was associated with significantly reduced
survival. These data can inform future research and construction of clinical
trials regarding short-term prophylaxis.
PMID- 29966168
TI - Early prenatal diagnosis of lysosomal storage disorders by enzymatic and
molecular analysis.
AB - OBJECTIVE: To report the 4-year experience of early prenatal diagnosis of
lysosomal storage disorders (LSDs) at a center in mainland China. METHOD: Forty
seven pregnancies affected with LSDs were assed using enzymes and/or molecular
studies. Prenatal studies were performed on 43 uncultured chorionic villi (CV)
samples, two amniotic fluid samples, and two umbilical cord blood samples.
RESULTS: Of the 47 fetuses, 23 (48.9%) were determined to normal, 13 (27.7%) to
be carriers, and 11 (23.4%) diagnosed as affected. In this cohort,
mucopolysaccharidoses (MPS) type II was the most common LSD, followed by Pompe
disease and then metachromatic leucodystrophy. In the 17 MPS II cases, the four
affected fetuses showed MPS II enzyme activity expression levels of 1.4% to 6.7%,
while the enzyme activity levels of the 13 normal fetuses ranged from 72% to
240.4%. In the seven Pompe cases, three fetuses were normal with Pompe enzyme
activity expression levels of 20%, 38.8%, and 77.3%, while four carrier
pregnancies showed enzyme activity levels of 17.5%, 17.5%, 33.4%, and 13.8%,
respectively. CONCLUSION: Based on different enzyme properties in uncultured CV,
different prenatal diagnostic strategies should be adopted for MPS II and Pompe
disease. Combining enzyme assay and molecular studies in uncultured CV improves
the reliability of prenatal diagnosis of LSDs.
PMID- 29966169
TI - Is an indistinct picture "exactly what we need"? Objectivity, accuracy, and harm
in imaging for cancer.
AB - Assumptions about the epistemic ideal of objectivity, closely related to
ontological assumptions about the nature of disease as pathophysiological
abnormality, lead us into oversimplified ways of thinking about medical imaging.
This is illustrated by current controversies in the early detection of cancer.
Improvements in the technical quality of imaging failed to address the problem of
overdiagnosis in breast cancer screening and exacerbate the problem in thyroid
cancer diagnosis. Drawing on Douglas and on Daston and Galison, I distinguish 3
dimensions of objectivity (accuracy, reliability, and precision) and demonstrate
ways they may be at odds, as illustrated in the early detection of cancer.
Guidelines for evaluating the efficacy of diagnostic imaging are insufficiently
sensitive to this complexity. Improving imaging quality may raise epistemic
issues, place disease definitions in question, and lead to overall harm or to
changes in the distribution of harms and benefits among population subgroups.
With a nod to Wittgenstein, I argue that we cannot take for granted that "an
indistinct picture" is not "exactly what we need."
PMID- 29966170
TI - Effect of extracorporeal low-energy shock wave on diabetic gastroparesis in a rat
model.
AB - BACKGROUND AND AIM: Delayed gastric emptying occurs in more than 50% of chronic
diabetic patients, and this is associated with significant impairments in quality
of life. Traditional therapy for delayed gastric emptying has focused on
supportive treatment, and there is no significant effective therapy. The effect
of low-energy shock wave on gastric motility is never studied. We investigated
low-energy shock wave on gastric motility in a diabetic rat model. METHODS:
Twenty-eight male Wistar rats were studied and separated in three groups in
randomized order as control, diabetic rats received shock wave, and diabetic rats
received the sham procedure. Antral area and motility were recorded using the
transabdominal ultrasound. Blood was taken for measurement of gastric motility
peptides. Subjects were killed for immunohistochemical stain analysis of enteric
plexus of the stomach. RESULTS: We successfully induced 20 diabetic rats and set
ultrasound for measuring rat gastric contract and emptying model and demonstrated
that 6 weeks of low-energy shock wave could promote gastric contraction and
emptying in diabetic rats. Moreover, we demonstrated that shock wave could
increase defecation and feces and decrease serum cholesterol and triglycerol.
However, no effect on glycohemoglobin and gastric motility peptides was recorded.
In the immunohistochemical staining, shock wave increased expression of gastric
myenteric neuron plexus. CONCLUSION: Low-energy shock wave can increase gastric
contraction and emptying by activating axonal regeneration and increasing
myenteric plexus, but not related with motility peptides.
PMID- 29966171
TI - Risk factors for pleural effusion recurrence in patients with malignancy.
AB - BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with
malignant pleural effusion (MPE) is symptom palliation. Currently, patients
undergo repeat thoracenteses prior to receiving a definitive procedure as
clinicians are not aware of the risk factors associated with fluid recurrence.
The primary objective of this study was to identify risk factors associated with
recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of
patients who underwent first thoracentesis was performed. The primary outcome was
time to fluid recurrence requiring intervention in patients with evidence of
metastatic disease. We used a cause-specific hazard model to identify risk
factors associated with fluid recurrence. We also developed a predictive model,
utilizing Fine-Gray subdistribution hazard model, and externally validated the
model. RESULTS: A total of 988 patients with diagnosed metastatic disease were
included. Cumulative incidence of recurrence was high with 30% of patients
recurring by day 15. On multivariate analysis, size of the effusion on chest X
ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI:
1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43
3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI:
1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004
1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative
cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased
hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural
effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology
were found to be risk factors for recurrence.
PMID- 29966172
TI - The development of a template for psychological assessment of women considering
risk-reducing or contralateral prophylactic mastectomy: A national Delphi
consensus study.
AB - OBJECTIVE: Risk-reducing mastectomies (RRM) and contralateral prophylactic
mastectomies (CPM) are increasingly prevalent strategies to reduce breast cancer
risk. Given the associated physical and emotional challenges, presurgical
psychological assessment is frequently recommended for this population, yet
limited research exists to guide this. This study aimed to reach a consensus on
the most relevant content and format of a psychological consultation prior to
RRM/CPM. METHODS: A modified two-round online Delphi study was conducted
Australia-wide. Expert participants (n = 25), including psychologists, surgeons,
nurses, oncologists, genetic specialists, and researchers completed a round-one
survey, informed by a literature review, previous qualitative study and expert
clinicians' input. This required participants to rate their agreement with 36
statements regarding potential content of a psychological consultation and
provide feedback on format/structure. A round-two survey comprised items that had
not reached consensus and six new items suggested by participants. Parameters for
statement consensus were set a priori at >75% agreement. RESULTS: Expert
participants indicated agreement with the majority of statements (39/42, 92.8%),
endorsing that the assessment should include (1) patient understanding of the
RRM/CPM procedure/cancer risk, (2) potential physical/emotional impact of
surgery, (3) informed decision-making, and (4) past/current psychological issues
(anxiety and body image). A provisional assessment template and user manual is
provided. CONCLUSIONS: This research culminated in a consensus-based template to
guide psychological assessment of women considering RRM/CPM. This enables health
professionals to assess suitability for surgery and preempt challenges within a
standardised framework. Future evaluation of the acceptability and effectiveness
of the template in clinical settings is warranted.
PMID- 29966173
TI - Metformin inhibits visceral allodynia and increased gut permeability induced by
stress in rats.
AB - BACKGROUND AND AIM: Metformin has been shown to have anti-cytokine property.
Lipopolysaccharide (LPS)-induced or repeated water avoidance stress (WAS)-induced
visceral allodynia and increased gut permeability were pro-inflammatory cytokine
dependent responses, which were considered to be animal models of irritable bowel
syndrome (IBS). We hypothesized that metformin improves symptoms in the patients
with IBS by attenuating these visceral changes and tested the hypothesis in rats.
METHODS: The threshold of the visceromotor response induced by colonic balloon
distention was measured. Colonic permeability was determined in vivo by
quantifying the absorbed Evans blue for 15 min spectrophotometrically. RESULTS:
Subcutaneously injected LPS (1 mg/kg) reduced the threshold of visceromotor
response, and metformin (5-50 mg/kg for 3 days) intraperitoneally attenuated this
response in a dose-dependent manner. Repeated WAS (1 h daily for 3 days) induced
visceral allodynia, which was also blocked by metformin. The antinociceptive
effect of metformin on the LPS-induced allodynia was reversed by compound C, an
adenosine monophosphate-activated protein kinase inhibitor or NG -nitro-L
arginine methyl ester, a nitric oxide synthesis inhibitor but not modified by
naloxone. Additionally, it was blocked by sulpiride, a dopamine D2 receptor
antagonist, but domperidone, a peripheral dopamine D2 receptor antagonist, did
not alter it. Metformin also blocked the LPS-induced or repeated WAS-induced
increased colonic permeability. CONCLUSIONS: Metformin attenuated the visceral
allodynia and increased gut permeability in animal IBS models. These actions may
be evoked via activation of adenosine monophosphate-activated protein kinase,
nitric oxide, and central dopamine D2 pathways. These results indicate the
possibility that metformin can be useful for treating IBS.
PMID- 29966174
TI - Chronic gout: Barriers to effective management.
AB - BACKGROUND: Gout is one of the most common inflammatory arthropathies, and the
pathogenesis is well understood. In Australia, most patients with chronic
tophaceous gout (CTG) are treated by general practitioners (GPs). Urate-lowering
therapy, if adhered to continuously, can suppress the disease, reduce the
likelihood of flares and prevent long-term complications such as disfiguring
tophi and joint damage. Many rheumatology societies recommend a treat-to-target
(T2T) approach, lowering serum urate to 0.35 mmol/L or below with urate lowering
therapy. OBJECTIVE: The aim of this article is to discuss inconsistencies in
treatment guidelines, identify patient and physician barriers to optimal gout
care, explain why a T2T approach is appropriate and make a series of
recommendations that are practical for GPs. DISCUSSION: Despite an in-depth
understanding of this controllable disease and the availability of simple, safe
treatments, chronic gout remains poorly managed. The development of Australian
gout guidelines that are easily implemented by GPs is vital and overdue.
PMID- 29966175
TI - Understanding and responding to problem sexual behaviours in children.
AB - BACKGROUND: One of the determinants of successful service engagement to address
problem sexual behaviours in children is the response when a parent/carer first
discloses the behaviour, often to a trusted professional such as a teacher,
allied health professional or the family general practitioner (GP). OBJECTIVE:
The objective of this article is to guide the response of medical professionals
to parents/carers of children exhibiting problem sexual behaviours, to increase
the likelihood of successful support service engagement. DISCUSSION: Problem
sexual behaviours in children can be a predictor of trauma or abuse, and their
discovery can have a devastating impact on parents and families, sometimes
leading to denial, blame, rejection and relationship breakdown. Understanding
parental reactions, using correct terminology, and responding with sensitivity
and understanding can increase the likelihood of successful service engagement
and intervention.
PMID- 29966176
TI - Care of patients with stomas in general practice.
AB - BACKGROUND: Intestinal stomas are formed for emergency, elective, benign and
malignant conditions. They may be temporary or permanent. The complication rates
of intestinal stomas are reported as high as 56%. OBJECTIVE: The aim of this
article is to provide an overview of intestinal stomas and common related issues,
to inform general practitioners (GPs) and improve stoma-related care. DISCUSSION:
There are a variety of early and late complications associated with intestinal
stomas. It is important that patients have access to an informed GP, stomal
therapy nurse and surgeon to provide optimal ongoing care. Good stoma care
contributes to good quality of life for patients.
PMID- 29966177
TI - Queensland tick typhus (Rickettsia australis) in a man after hiking in
rural Queensland.
PMID- 29966178
TI - Evidence-based medicine.
PMID- 29966179
TI - 'Why don't I need a colonoscopy?' A novel approach to communicating risks and
benefits of colorectal cancer screening.
AB - BACKGROUND AND OBJECTIVES: There is significant growth in demand for
colonoscopies, with over 700,000 performed in Australia in 2012-13. For every one
million Australians aged 50 years and older, 80,000 people at average risk of
colorectal cancer are being over-screened with colonoscopy, and 29,000 people at
increased risk are not having the colonoscopy they need. METHOD: Using monitoring
data from the Australian National Bowel Cancer Screening Program and published
data on colonoscopic screening, we have developed expected frequency trees (EFTs)
to demonstrate projected outcomes of different colorectal cancer screening
options for participants at different levels of colorectal cancer risk in
Australia. RESULTS: The EFTs highlight the overall balance in favour of faecal
occult blood screening for those at average risk in terms of fewer deaths and
complications. DISCUSSION: This novel method of risk communication can be used to
promote appropriate patient choice of colorectal cancer screening modality and
potentially reduce the number of referrals for colonoscopy in patients who are
not at increased risk of colorectal cancer.
PMID- 29966180
TI - Interpreting evidence in general practice: Bias and conflicts of interest.
AB - BACKGROUND: Sponsorship of research and education occurs commonly in the
pharmaceutical, medical device, and food and drink industries. This sponsorship
is a conflict of interest, creating a situation where there may be bias in favour
of the sponsors' interests. General practitioners (GPs) need to be aware of
potential conflicts of interest in industry-sponsored research and education.
OBJECTIVE: The aim of this article is to alert GPs to the risk of bias in
research and education funded by for-profit organisations, and to provide
strategies to avoid being influenced by information that may be biased.
DISCUSSION: Types of bias known to be associated with industry sponsorship
include: methodological bias, where there is a systematic error in the design,
conduct or analysis of the study such that it deviates from the truth; agenda
bias, where study topics align with increased use of industry products;
publication and reporting bias, where unfavourable studies or results are
suppressed or omitted; and marketing bias, where supportive evidence is
preferentially disseminated and sympathetic opinion leaders are given a broad
platform. Industry influence can be reduced by seeking out independent reviews
and avoiding industry-funded educational events.
PMID- 29966181
TI - Evaluating and prescribing new medicines in general practice.
AB - BACKGROUND: In Australia, the Therapeutic Goods Administration (TGA) approves new
medicines that general practitioners (GPs) may prescribe. Medicines listed under
the Pharmaceutical Benefits Scheme (PBS) have undergone a rigorous independent
evaluation in relation to comparative efficacy, safety and effectiveness against
medicines already on the market. However, GPs need to appraise the medicines they
prescribe for individual patients, taking a number of factors into consideration.
OBJECTIVE: The aim of this article is to assist GPs' decision making when
prescribing new medicines, and provide information about the most reliable
sources of unbiased information to help them evaluate the risks and benefits in
partnership with their patients. DISCUSSION: GPs require accurate summaries of a
medicine's properties, efficacy and side-effect profile from trusted sources such
as the Australian Medicines Handbook, Therapeutic Guidelines, NPS MedicineWise,
Australian Prescriber or the TGA. Information about a new medicine needs to be
interpreted so that patients may also make informed choices.
PMID- 29966182
TI - Unlocking the value of Cochrane reviews for general practitioners.
AB - BACKGROUND: Cochrane reviews are difficult to construct and may be difficult to
read, but they produce trusted, high-quality research responses to common
clinical questions. OBJECTIVE: The objective of this article is to help
clinicians navigate the Cochrane Library and Cochrane reviews. Using a common
clinical scenario, we illustrate how to find the information required to guide
evidence-based decision making with patients. DISCUSSION: Clinicians looking for
answers to clinical questions often turn first to guidelines. However, these may
not provide enough background to balance the pros and cons of a treatment.
Cochrane reviews often inform guidelines and contain more in-depth clinical
information for shared decision making. The introduction of Summary of Findings
(SoF) tables has made the studies in Cochrane reviews more accessible. In this
paper, we discuss how to read and interpret these SoF tables. Additional
resources, such as journal summaries and podcasts, have also improved the
accessibility of Cochrane review findings.
PMID- 29966183
TI - Trauma-informed care in general practice: Findings from a women's health centre
evaluation.
AB - BACKGROUND AND OBJECTIVES: Trauma and adversity have serious health consequences,
particularly when experienced in early life. These health consequences can be
significantly lessened if young people access appropriate care when needed. In
2004, the Blue Mountains Women's Health and Resource Centre created a Young
Women's Clinic (YWC) that began providing drop-in appointments for women aged 12
25 years with a general practitioner, nurse or counsellor, as well as a group art
program. METHOD: A qualitative evaluation of services provided by the YWC was
conducted, drawing on 13 years of client and staff experiences. The evaluation
framework was drawn from the recommendations of the NSW Centre for Advancement of
Adolescent Health, the Australian Women's Health Network and the World Health
Organization report on People-centred and integrated health services. RESULTS:
The following principles of trauma-informed care were identified in the study:
recognising the impact of trauma on consultations; tailoring consultation length
to client needs; providing trauma therapy as well as physical healthcare;
offering long-term, safe relationships with staff; trauma-sensitive
gynaecological care; and the importance of self-care for health practitioners.
DISCUSSION: Our findings demonstrate the importance of holistic general practice
services in preventing and managing the long-term health consequences of
adversity and trauma.
PMID- 29966184
TI - General practitioners' perspectives on promoting sexual health to young men.
AB - BACKGROUND AND OBJECTIVES: General practitioners (GPs) are well placed to promote
sexual health to young men. Our previous research has suggested that this
population expect GPs to initiate sexual health promotion. Little is known of
GPs' perceptions of their role in sexual health promotion and perceived needs of
young men. METHOD: Semi-structured interviews with GPs were recorded until data
saturation. Data were managed with NVivo; consensus was reached on thematic
analysis. RESULTS: In 17 semi-structured interviews, a young man symptomatic
with a sexually transmissible infection (STI) was the most common sexual health
presentation. GPs identified a range of barriers to, and facilitators, of
initiating discussions about sexual health. Some GPs reported no young male
sexual health presentations. GPs generally believed young men should be taking
more responsibility for their sexual health. DISCUSSION: Only some GPs endorsed
young men's expectations that the GP would initiate a sexual health discussion.
Increased awareness that young men are unlikely to seek sexual health advice
would allow GPs to better tailor their approaches and increase opportunistic
testing and sexual health promotion.
PMID- 29966185
TI - Patient-directed reminders to improve preventive care in general practice for
patients with type 2 diabetes: A proof of concept.
AB - BACKGROUND AND OBJECTIVES: Preventive care in general practice is fundamental to
managing the Australian diabetes epidemic. Recommended preventive care is
nonetheless underperformed. The aim of this pilot study was to demonstrate proof
of concept that pre-consultation patient-directed reminders could improve
preventive care in general practice. METHOD: Over two weeks, four general
practices used a special software tool to generate reminder sheets listing
recommended checks for a subset of patients with type 2 diabetes mellitus (T2DM).
The sheets were given to patients before their consultations. The number of
checks performed was compared for patients who did and did not receive reminders.
General practitioners (GPs) were interviewed about the reminders and chronic
disease management. RESULTS: Patients who received reminders had more recommended
checks performed than those who did not receive reminders. GPs found the
reminders useful but suggested that broader system changes are required.
DISCUSSION: Pre-consultation patient-directed reminders could potentially be an
effective tool to increase preventive care for patients with T2DM in general
practice.
PMID- 29966186
TI - Medical student contact with specialty trainees: Missing out in general practice?
AB - BACKGROUND AND OBJECTIVES: Medical students on clinical placements value positive
experiences with specialty trainees. We aimed to document student contact with
general practice registrars and other specialty registrars and any relationship
between this contact and student career interests. METHOD: Medical students were
surveyed following their general practice, general medicine, general surgery,
psychiatry and medicine-in-society placements. RESULTS: One hundred and twenty
four students completed the survey (73% response rate). Participants reported
substantially less contact with general practice registrars and rural generalist
trainees than with other registrars. Compared with students placed in regional
areas, metropolitan students were more likely to have no contact at all with
general practice registrars. Interest in specialty careers was correlated with
interest in knowing more about specialty training, but not with the extent of
contact with registrars or personal connections in any specialty studied.
DISCUSSION: Student exposure to general practice registrars in at least one
Australian medical school is relatively low. Opportunities to increase this
should be explored. Students themselves may have little influence over their
contact with specialty trainees, despite valuing it highly.
PMID- 29966187
TI - Shared decision making in multimorbidity.
PMID- 29966188
TI - Effects of robot assistive upper extremity rehabilitation on motor and cognitive
recovery, the quality of life, and activities of daily living in stroke patients.
AB - OBJECTIVE: To evaluate the effects of robotic rehabilitation on upper extremity
functions, cognitive development, and activities of daily living in patients with
subacute stroke. METHODS: This study was set as prospective and controlled.
Subjects with subacute stroke were allocated into two groups as the robotic and
control groups. All subjects received a conventional rehabilitation program five
times a week for 3 weeks. In addition, robotic group received robotic
rehabilitation five times a week for 3 weeks (30 minutes per session). RESULTS:
There were 20 patients in the robotic group (mean age of 63.27 +/- 3.88 years)
and 15 patients in the control group (mean age of 59.25 +/- 8.10 years). Compared
with baseline, the Functional independence measure (both motor and cognitive
subscale), Fugl-Meyer Assessment Scale, and Motricity Index values did increase
in both groups. Change levels of Fugl-Meyer Assessment FMA
shoulder/elbow/forearm, and Motricity Index shoulder scores were significantly
higher in the robotic group than the control group (p< 0.05). Compared with the
baseline, physical component summary scores improved only in the robotic group,
yet motor component summary scores improved only in the control group. Although
Brunnstrom levels increased in both groups compared with baseline, change levels
were similar. CONCLUSION: In the light of our results, robotic rehabilitation in
addition to the conventional rehabilitation program seems to be effective on
improving motor recovery and the quality of life in subacute stroke patients.
PMID- 29966189
TI - Limb-girdle muscular dystrophy type 2B: An unusual cause of proximal muscular
weakness in Saudi Arabia.
AB - Dysferlinopathies encompass a group of neuromuscular diseases characterized by
the absence of dysferlin in skeletal muscle. It is a genetic disorder caused by a
mutation in the dysferlin gene (DYSF) with an autosomal recessive mode of
inheritance. In this article, we report a case of Limb-girdle muscular dystrophy
type 2B with a rare homozygous duplication c.164dupA, p.(Ile57Hisfs*8)
(rs863225020) in DYSF in a Saudi patient. To the best of our knowledge, this is
the first case from Saudi Arabia with complete clinical data, pathology findings,
radiology findings, and genetic analysis. Although there is no curative treatment
for this disease, an accurate diagnosis is important to avoid using steroids and
immunosuppressive medications, which are not effective and may have several side
effects. Further studies are needed to explore potential therapies for this rare
condition.
PMID- 29966190
TI - Alzheimer's Disease Computer-Aided Diagnosis: Histogram-Based Analysis of
Regional MRI Volumes for Feature Selection and Classification.
AB - This paper proposes a novel fully automatic computer-aided diagnosis (CAD) system
for the early detection of Alzheimer's disease (AD) based on supervised machine
learning methods. The novelty of the approach, which is based on histogram
analysis, is twofold: 1) a feature extraction process that aims to detect
differences in brain regions of interest (ROIs) relevant for the recognition of
subjects with AD and 2) an original greedy algorithm that predicts the severity
of the effects of AD on these regions. This algorithm takes account of the
progressive nature of AD that affects the brain structure with different levels
of severity, i.e., the loss of gray matter in AD is found first in memory-related
areas of the brain such as the hippocampus. Moreover, the proposed feature
extraction process generates a reduced set of attributes which allows the use of
general-purpose classification machine learning algorithms. In particular, the
proposed feature extraction approach assesses the ROI image separability between
classes in order to identify the ones with greater discriminant power. These
regions will have the highest influence in the classification decision at the
final stage. Several experiments were carried out on segmented magnetic resonance
images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) in order to
show the benefits of the overall method. The proposed CAD system achieved
competitive classification results in a highly efficient and straightforward way.
PMID- 29966191
TI - The Impact of Hospitalization on Readmission, Institutionalization, and Mortality
of People with Dementia: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: People with dementia (PwD) are at a high risk of hospitalization.
Hospitals are often not adequately equipped for PwD and discharges often come
unexpected. Therefore, PwD are at a risk of adverse outcomes. However,
information about those outcomes is rare but crucial for the development of
preventive strategies. OBJECTIVES: To conduct a quantitative systematic review
and meta-analyses on the impact of a hospitalization on readmission,
institutionalization, and mortality in PwD. To identify factors associated with
these outcomes. METHODS: PubMed, CENTRAL, and ScienceDirect were searched for
studies including terms for dementia, hospital, readmission,
institutionalization, and mortality. Relevant were assessed by a quality criteria
sheet. Results were summarized in a table. Meta-analysis was conducted with
Review Manager 5.3. RESULTS: The search yielded 1,108 studies; 20 fulfilled the
inclusion criteria and 10 studies were eligible for meta-analyses. The incidence
and relative risk (RR) of mortality (RR 1.74 CI95 % 1.50, 2.05) and
institutionalization (RR: 2.16 CI95 % 1.31, 3.56) of PwD was significantly higher
when compared to people without dementia. Results according to readmission rate
were inconsistent. Factors significantly associated with the examined adverse
outcomes were severity of dementia, number of medications, and deficits in daily
living activities. CONCLUSION: Hospitalization of PwD lead to adverse outcomes.
An improvement in the identification of and care for PwD in the acute setting as
well as in after care in the community setting, especially in the interface
between both settings, is required to prevent adverse outcomes in hospitalized
PwD.
PMID- 29966192
TI - Lower Serum Antibodies Against Tau Protein and Heavy Neurofilament in Alzheimer's
Disease.
AB - BACKGROUND: Unlike antibodies against amyloid-beta, little is known about serum
antibodies to neuron-specific cytoskeletal proteins in patients with Alzheimer's
disease (AD). OBJECTIVE: We aimed to study IgG autoantibodies against tau
protein, light (NFL) and heavy subunits (NFH) of neurofilaments in serum of AD
patients and elderly controls and to explore the evolution of
antineurocytoskeletal antibody levels over time. METHODS: Antibodies against
three targets (tau, NFL, and NFH) were measured using ELISA in 100 serum samples
from 51 cognitively normal elderly controls and 49 patients with AD. Our primary
cross-sectional design was further extended to monitor fluctuations over 1-2
years in a subset of individuals. RESULTS: The AD patients had lower levels of
anti-tau antibodies (p = 0.03) and even lower anti-NFH antibodies (p = 0.005)
than those in the control group at baseline. On the contrary, anti-NFL antibodies
or total IgG concentrations in serum did not differ. All three antibodies
remained stable in both groups except for a selective and significant anti-tau
decline in AD patients (p = 0.03). CONCLUSIONS: The different responses to these
antigens suggest some antibody selectivity in AD. The significant decline was
observed for only serum anti-tau antibodies in AD patients over time and it
corresponds to lower anti-tau levels in these patients. Our findings indicate a
special feature of disease-relevant antigens and humoral autoimmunity in AD.
PMID- 29966193
TI - Music and Dementia: Individual Differences in Response to Personalized Playlists.
AB - Personalized music playlists are increasingly being used in health-care contexts
to address the psychological and behavioral symptoms in people with dementia.
However, there is little understanding of how people with different mental health
histories and symptoms respond differently to music. A factorial experiment was
conducted to investigate the influence of depression, anxiety, apathy, and
cognitive decline on affective response to music. Ninety-nine people with
dementia listened to three music playlists based on personal preferences.
Activation of facial action units was measured, and behavioural responses
continuously observed. Results demonstrated that people with high levels of
depression and with symptoms of Alzheimer's type dementia demonstrated increased
levels of sadness when listening to music. People with low depression but high
levels of apathy demonstrated the highest behavioral evidence of pleasure during
music listening, although behavioral evidence declined with severity of cognitive
impairment. It is concluded that as well as accounting for personal preferences,
music interventions for people with dementia need to take mental health history
and symptoms into account.
PMID- 29966195
TI - Rapidly Progressive Alzheimer's Disease in Two Distinct Autopsy Cohorts.
AB - BACKGROUND: A rapidly progressive phenotype of Alzheimer's disease (AD) has been
described in some prion disease cohorts. Limited information regarding rapidly
progressive AD (rpAD) is available from longitudinal national cohorts. OBJECTIVE:
To compare the clinical characteristics of rpAD in two different national
cohorts. METHODS: A retrospective analysis was performed on AD subjects with
available neuropathology in the National Alzheimer's Coordinating Center (NACC)
database and among neuropathologically characterized AD cases from the National
Prion Disease Pathology Surveillance Center (NPDPSC) that were evaluated for
suspected prion disease. In the NACC cohort, rpAD was delineated by the lower
10th percentile of follow up duration from pre-dementia to death duration among
subjects meeting pathological diagnosis of AD. RESULTS: rpAD from the NPDPSC had
a shorter mean symptom duration than the NACC identified rpAD cases (11.6 months
versus 62.4 months) and were also younger at the time of their death (60.0 versus
81.8 years). NACC identified rpAD subjects, beginning from a predementia stage,
had slower rate of MMSE change per year than NPDPSC cases (2.5 versus 6.0
points). CONCLUSIONS: rpAD constitute an important subset of AD subjects in whom
a rapid course of symptomatic clinical decline is noted, as confirmed in both
national cohorts. rpAD was best characterized by survival time (<=3 years), as
there were clear differences between the rpAD cohorts in terms of symptom
duration, age at death, and MMSE change per year, likely due to the strong
selection biases. rpAD could shed light on the biology of rate of progression in
AD.
PMID- 29966194
TI - Diaphanous 1 (DIAPH1) is Highly Expressed in the Aged Human Medial Temporal
Cortex and Upregulated in Myeloid Cells During Alzheimer's Disease.
AB - BACKGROUND: The receptor for advanced glycation end products (RAGE) is linked to
cellular stress and inflammation during Alzheimer's disease (AD). RAGE signals
through Diaphanous-1 (DIAPH1); however, the expression of DIAPH1 in the healthy
and AD human brain has yet to be methodically addressed. OBJECTIVE: To delineate
the cell- and disease-state specific expression of DIAPH1 in the human medial
temporal cortex during healthy aging and AD. METHODS: We used semi-quantitative
immunohistochemistry in the human medial temporal cortex paired with widefield
and confocal microscopy and automated analyses to determine colocalization and
relative expression of DIAPH1 with key cell markers and molecules in the brains
of subjects with AD versus age-matched controls. RESULTS: We report robust
colocalization of DIAPH1 with myeloid cells and increased expression during AD,
which strongly correlated to increased neutral lipids and morphology of inflamed
myeloid cells. DIAPH1 moderately colocalized with markers of endothelial cells,
astrocytes, neurons, and oligodendrocytes. DISCUSSION: Our findings localize
DIAPH1 particularly to myeloid cells in the CNS, especially in AD in the
locations of lipid droplet accumulation, thereby implicating RAGE-DIAPH1
signaling in dysregulated lipid metabolism and morphological changes of inflamed
myeloid cells in this disorder.
PMID- 29966196
TI - In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric
Peptides Developed for the Treatment of Alzheimer's Disease.
AB - Diffusible amyloid-beta (Abeta) oligomers are currently presumed to be the most
cytotoxic Abeta assembly and held responsible to trigger the pathogenesis of
Alzheimer's disease (AD). Thus, Abeta oligomers are a prominent target in AD drug
development. Previously, we reported on our solely D-enantiomeric peptide D3 and
its derivatives as AD drug candidates. Here, we compare one of the most promising
D3 derivatives, ANK6, with its tandem version (tANK6), and its head-to-tail
cyclized isoform (cANK6r). In vitro tests investigating the D-peptides' potencies
to inhibit Abeta aggregation, eliminate Abeta oligomers, and reduce Abeta-induced
cytotoxicity revealed that all three D-peptides efficiently target Abeta.
Subsequent preclinical pharmacokinetic studies of the three all-D-peptides in
wildtype mice showed promising blood-brain barrier permeability with cANK6r
yielding the highest levels in brain. The peptides' potencies to lower Abeta
toxicity and their remarkable brain/plasma ratios make them promising AD drug
candidates.
PMID- 29966197
TI - Predictors of Delirium Development in Older Medical Inpatients: Readily
Identifiable Factors at Admission.
AB - BACKGROUND: Identifying patients at high risk of delirium is crucial to
facilitate prevention. Although dementia is the most consistent risk factor
across populations, it remains under-diagnosed. Hence understanding other markers
of delirium vulnerability on admission is important. OBJECTIVE: We aimed to
identify predictors of incident delirium development in older medical inpatients
that were readily identifiable at presentation to the emergency department.
METHODS: Medical inpatients of >=70 years were assessed on admission for delirium
using the Revised Delirium Rating Scale (DRS-R98) and those with prevalent
delirium were excluded. Consenting non-delirious patients were then assessed
daily using the DRS-R98. Data pertaining to multiple baseline delirium risk
factors were collected, including pre-morbid dementia. Multivariable logistic
regression was used to examine which factors predicted the development of
incident delirium. RESULTS: Of 555 patients approached, 184 (33.1%) had prevalent
delirium. Following other exclusions, 191 were included in the study and 61
developed incident delirium. Predictors of incident delirium on multivariable
analysis, controlling for confounders, were dementia (OR 2.54, 95% CI 1.01-6.43,
p = 0.048); Barthel Index score (OR 1.15 for each unit decrease in score, 95% CI
1.06-1.25, p = 0.001), and Modified Cumulative Illness Rating Scale score (OR
1.13 for each unit increase in score, 95% CI 1.05-1.22, p = 0.001). CONCLUSION:
Dementia is a well-known risk factor for delirium; however, it too is under
recognized and on admission can be missed. Conversely, the Barthel Index is a
simple and widely used measure of functional ability that may prove useful in
stratifying those at risk of in-hospital delirium on admission.
PMID- 29966198
TI - miRNA 933 Expression by Endothelial Cells is Increased by 27-Hydroxycholesterol
and is More Prevalent in Plasma from Dementia Patients.
AB - Alzheimer's disease (AD) etiology is complex; gene and environmental risk factors
may interact to predispose to disease. From single nucleotide polymorphism
analyses and genome-wide association studies, a number of candidate risk genes
for the onset of AD have been identified and cluster around lipid metabolism and
inflammation. We hypothesized that endothelial cells which line the blood-brain
barrier are likely to be critical mediators of systemic metabolism within the
brain. Therefore, we have studied the effect of 27 hydroxycholesterol (27-OHC) on
microvascular endothelial cell (HMVEC) redox state, inflammatory cytokine
secretion, and microRNA (miR) expression. Using a transwell method, we have
studied directional secretion profiles for the proinflammatory cytokines TNFalpha
and IL-6 and confirmed that 27-OHC induces discrete and directional inflammatory
molecular signatures from HMVEC. The lipids caused depletion of cellular
glutathione and cytokine secretion is HMVEC-redox state-dependent. Discovery miR
expression change in HMVEC with and without 27-OHC treatment was undertaken. We
selected three genes for further analysis by qPCR; miR-144 and 146 expression,
which are anti-inflammatory and redox regulating modulators, were not affected
significantly by 27-OHC. However, increased expression of a putative neurotrophic
regulatory factor miR933 in HMVEC with 27-OHC was confirmed by qPCR. In plasma
from patients with dementia, all three miR were found at significantly elevated
levels compared to healthy older adults. These data highlight that 27-OHC has an
important regulatory effect on endothelial microvascular cells to increase
expression of a miR (-933) and secretion of inflammatory cytokines that are
elevated in plasma from dementia patients.
PMID- 29966199
TI - Association of Motoric Cognitive Risk Syndrome with Cardiovascular Disease and
Risk Factors: Results from an Original Study and Meta-Analysis.
AB - BACKGROUND: Motoric cognitive risk (MCR) syndrome, a recently described pre
dementia syndrome, has been associated with cardiovascular disease and their risk
factors (CVDRF). OBJECTIVE: To determine whether MCR syndrome was associated with
CVDRF in French community-dwelling older adults, and to quantitatively evaluate,
with a systematic review and meta-analysis, the association of MCR syndrome with
CVDRF. METHODS: Based on a cross-sectional design, 238 older adults without
dementia were selected from the French GAIT study. An English and French
systematic Medline and Embase search (without limiting date of publication) was
also conducted in February 2017 using the terms "motoric cognitive risk syndrome"
OR "motoric cognitive risk" OR "motoric risk". The systematic review and meta
analysis included 8 studies. CVDRF were defined as cardiovascular diseases,
hypertension, diabetes, stroke, obesity and abnormal waist-hip ratio (WHR).
RESULTS: The prevalence of MCR syndrome in the current original study was 16.8%.
MCR syndrome was associated with abnormalWHR(Odds ratio [OR] >2.8 with p < 0.020)
and high blood pressure (OR >2.5 with p < 0.025). Of the 202 originally
identified abstracts, 7 (3.5%) were selected for the systematic review. The meta
analysis showed that all pooled OR were significant with a p-value <0.001 (OR =
1.41 for cardiovascular diseases, 1.21 for hypertension, 1.44 for diabetes, 2.05
for stroke, and 1.34 for obesity). When pooling all CVDRF, the overall OR was
1.38 (95% CI, 1.33-1.45) with p-value <0.001. CONCLUSION: MCR syndrome is
significantly associated with CVDRF. These findings suggest that a vascular
mechanism may underlie the pathophysiology of MCR syndrome.
PMID- 29966200
TI - In Vivo MRI of Amyloid Plaques in a Cholesterol-Fed Rabbit Model of Alzheimer's
Disease.
AB - Hypercholesterolemia has been identified as a risk factor for Alzheimer's
disease. In this study, rabbits were fed either a cholesterol diet or normal chow
diet for 24 months. At endpoint, in vivo MRI was performed at the field strength
of 3 Tesla using fast imaging employing steady state acquisition without (FIESTA)
or with susceptibility-weighted post-processing (SWI-FIESTA) and susceptibility
weighted imaging with multi-echo acquisition (SWAN). This imaging revealed signal
voids/hypointensities throughout the cortex, sub-cortex, and hippocampus of
cholesterol-fed animals compared to control animals. Quantitative image analysis
corroborated these qualitative findings and highlighted that SWI processing of
FIESTA images significantly improved the detectability of plaques (p < 0.05).
Abeta immunostaining and Prussian blue staining for iron demonstrated that the
voids in MR images corresponded to iron-laden Abeta-positive plaques. This study
demonstrates non-invasive in vivo visualization of Abeta plaques in a diet
induced large animal model of Alzheimer's disease. This work lays the foundation
for future work focusing on longitudinal monitoring of plaque formation in this
model and the effects of diet or drug interventions.
PMID- 29966201
TI - Distribution of Cerebrospinal Fluid Biomarker Profiles in Patients Explored for
Cognitive Disorders.
AB - BACKGROUND: CSF Alzheimer's disease (AD) biomarkers allow classifying individuals
based on their levels of amyloid and neurodegeneration pathologies. OBJECTIVE: To
investigate the distribution of AD biomarker profiles from patients suffering
from cognitive disorders. METHODS: We analyzed 3001 patients with cognitive
disorders and referred by 18 French memory clinics located in and around Paris.
Patients were classified as normal, amyloidosis (A+/N-), amyloidosis and
neurodegeneration (A+/N+) or suspected non-AD pathophysiology (SNAP), according
to their CSF levels of biomarkers. Analysis were performed for the overall
population and stratified by gender, age quintiles, and Mini-Mental State
Examination (MMSE) score quintiles. Results were compared to previous findings in
cohorts of healthy elderly adults. RESULTS: 37% of the sample were classified as
A+/N+, 22% were classified A+/N-, and 15% as SNAP. The A+/N+ profile was
associated with female gender, advanced age, and lower MMSE score, while the A+/N
profile was observed more frequently in men and the distribution was stable
across age and MMSE. The SNAP profile showed no association with gender or age,
was less frequent in patients with lower MMSE, and had a lower repartition than
the one previously reported in asymptomatic populations. CONCLUSIONS: While A+/N+
patients had the clinical characteristics typically observed in AD, A+/N-patients
had a different epidemiological pattern (higher frequency in men, no association
with advanced age or lower MMSE). The SNAP profile was less frequent than
previously reported in the general elderly population, suggesting that this
profile is not a frequent cause of memory impairment in this population.
PMID- 29966202
TI - Real-World, Multinational, Retrospective Observational Survey of the ADAS-Cog and
Associations with Healthcare Resource Utilization in Patients with Alzheimer's
Disease.
AB - BACKGROUND: Alzheimer's disease (AD) is one of the most costly conditions, both
economically and regarding patient disability and dependency. The huge costs
coupled with the predicted increase in prevalence worldwide are likely to
challenge healthcare systems in the future. The classic version of the
Alzheimer's Disease Assessment Scale-Cognition subscale (ADAS-Cog) is generally
seen as the current gold standard primary outcome measure of cognitive symptom
progression in dementia clinical trials. OBJECTIVE: This study evaluated the
relationship between ADAS-Cog scores as a measure of clinical progression and the
healthcare resource utilization (HCRU)-measured burden of cognitive impairment in
patients with mild cognitive impairment, AD, or suspected AD in the real world.
METHODS: A retrospective observational survey of physicians and their consulting
patients with multiple ADAS-Cog scores. Regression models were constructed for
HCRU variables (e.g., consultations, hospitalizations, caregiving requirements)
with ADAS-Cog rate of change, baseline ADAS-Cog, and their interaction included
as exposure variables. RESULTS: 651 patient records were completed by 154
physicians. Approximately 70% of patients had mild to moderate dementia. In 56.7%
of patients, clinical progression was maintained/stable from baseline. Mean
change in ADAS-Cog (adjusted to 12 months) was 2.8 points and change scores
increased with increasing dementia severity. Most HCRU variables increased
significantly (p < 0.05; joint test) with increasing ADAS-Cog scores (indexing
clinical deterioration). CONCLUSION: The results suggest that further
understanding the relationship between HCRU and ADAS-Cog changes in real-world
clinical practice could potentially provide a baseline upon which the success of
disease-modifying, as well as newer symptomatic, dementia therapies can be
judged.
PMID- 29966203
TI - Diosgenin Attenuates Lipopolysaccharide-Induced Parkinson's Disease by Inhibiting
the TLR/NF-kappaB Pathway.
AB - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease characterized
by loss of dopaminergic neurons in the substantia nigra. Diosgenin is a natural
steroid saponin which was shown to play a beneficial role in Alzheimer's disease.
OBJECTIVE: This study sought to investigate the potential effect of diosgenin on
a rat model of PD. METHODS: Sprague Dawley rats were subjected to intra-striatal
injection of lipopolysaccharide (LPS) and treated with diosgenin. Stepping,
Whisker, and Cylinder tests were carried out to determine the motor function, and
the expression of tyrosine hydroxylase was detected by immunohistochemistry. The
levels of multiple proinflammatory cytokines, oxidative stress related factors
and proteins involved in Toll-like receptor (TLR)/nuclear factor kappa B (NF
kappaB) pathway were measured. The synergistic effect of environment enrichment
on diosgenin was also investigated. RESULTS: Intra-striatal injection of LPS
caused motor deficits in rats, induced inflammatory response and oxidative stress
response, and activated the TLR/NF-kappaB pathway both in vivo and in vitro.
Diosgenin could attenuate the LPS-induced alterations. Enriched environment
enhanced the effect of diosgenin to ameliorate the LPS-induced motor deficits in
rats and decreased the protein levels of TLR2, TLR4, and nuclear NF-kappaB in
diosgenin treated PD rats. CONCLUSION: Diosgenin had a beneficial effect in LPS
induced rat PD models, by suppressing the TLR/NF-kappaB signaling pathway.
Environmental enrichment could play a synergistic effect with diosgenin, by
enhancing the inhibitory effect of diosgenin on the TLR/ NF-kappaB signaling
pathway.
PMID- 29966204
TI - Do Cardiometabolic Risk Factors Influence Amyloid, Tau, and Neuronal Function in
APOE4 Carriers and Non-Carriers in Alzheimer's Disease Trajectory?
AB - Cardiovascular risk could be calculated using Qrisk2. It is suggested that
cardiovascular risk factors influence the progression of Alzheimer's disease
(AD). However, studies have not specifically evaluated the influence of
cardiovascular risk using Qrisk2 on neuropathological progression and AD
biomarkers. The aim of the study was to evaluate the influence of cardiovascular
risk factors using Qrisk2 on CSF amyloid-beta (Abeta) and tau, 18F-AV45-PET, 18F
FDG-PET, MRI, and cognitive measures in APOE4 negative cognitively normal and
mild cognitive impairment (MCI) subjects. 614 cognitively normal, early, and late
MCI subjects were selected from the ADNI cohort with a 2-year follow-up. CSF
Abeta and tau, 18F-AV45-PET, 18F-FDG-PET, MRI, and cognitive measures along with
modified Qrisk2 were evaluated. APOE4 non-carrier, high cardiovascular risk sub
group of early and late MCI and cognitively normal subjects, demonstrated worse
biomarker and cognitive profile at baseline and during follow up compared to low
cardiovascular risk group. Additionally, similar pattern was also observed in
APOE4 carriers. We demonstrated that Qrisk2 and APOE4 were independent predictors
of biomarker and clinical progression in AD trajectory. High cardiovascular risk
is associated with biomarker changes in APOE4 non-carriers in prodromal AD, which
may suggest that treatment of cardiovascular risk is an effective prevention
strategy even in APOE4 negative subjects and may influence disease progression
independent of amyloid pathology. Demonstration of accelerated neuropathological
changes in both APOE4 carriers and non-carriers suggest that focusing on
modifiable cardiovascular risk factors is an effective preventative strategy
while we eagerly waiting for new treatments.
PMID- 29966205
TI - 15th International Congress on Neuromuscular Diseases, July 6 - 10, 2018 Vienna,
Austria.
PMID- 29966207
TI - Kufor-Rakeb Syndrome/PARK9: One Novel and One Possible Recurring Ashkenazi
ATP13A2 Mutation.
AB - Kufor-Rakeb syndrome (KRS)/PARK9 presents with autosomal recessive young onset
Parkinson's disease (YOPD), spastic paraparesis, abnormal eye movements and
facial myokymia. KRS is caused by homozygous/compound heterozygous inactivating
mutations in ATP13A2. Two affected siblings (born to non-consanguineous Jewish
parents) presenting a similar KRS phenotype (onset age 27, 23), carried compound
heterozygous pathogenic variants in ATP13A2: c.217_218insG and c.3057delC. Allele
frequency of the c.3057delC mutation was about 100 times higher in Ashkenazi
controls in our study (1/190 = 0.00526) and in the Genome Aggregation Database,
(GnomAD, 27/10132 = 0.002665) versus non-Ashkenazi controls worldwide in GnomAD
(9/264566 = 0.000034018, p < 0.0001). The c.217_218insG mutation is novel and not
found in controls or GnomAD. The c.3057delC mutation should be included in the
genetic workup of Ashkenazi YOPD patients.
PMID- 29966206
TI - Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in
Parkinson's Disease.
AB - While a small subset of Parkinson's disease cases have genetic causes, most cases
are sporadic and may have an environmental contributor that has largely remained
enigmatic. Remarkably, gastrointestinal symptoms in PD patients serve as a
prodrome for the eventual motor dysfunctions. Herein, we review studies exploring
a possible link between the gastric human pathogen Helicobacter pylori and PD. We
provide plausible and testable hypotheses for how this organism might contribute
to PD: 1) a toxin(s) produced by the bacteria; 2) disruption of the intestinal
microbiome; 3) local inflammation that crosses the gut-brain axis, leading to
neuroinflammation; and 4) manipulation of the pharmacokinetics of the PD drug
levodopa by H. pylori, even in those not receiving exogenous levodopa. Key
findings are: 1) people with PD are 1.5-3-fold more likely to be infected with H.
pylori than people without PD; 2) H. pylori-infected PD patients display worse
motor functions than H. pylori-negative PD patients; 3) eradication of H. pylori
improves motor function in PD patients over PD patients whose H. pylori was not
eradicated; and 4) eradication of H. pylori improves levodopa absorption in PD
patients compared to that of PD patients whose H. pylori was not eradicated.
Evidence is accumulating that H. pylori has a link with PD, but the mechanism is
unclear. Future work should explore the effects of H. pylori on development of PD
in defined PD animal models, focusing on the roles of H. pylori toxins,
inflammation, levodopa absorption, and microbiome dysbiosis.
PMID- 29966208
TI - Perinatal asphyxia in a rural Nigerian hospital: Incidence and determinants of
early outcome.
AB - BACKGROUND: Perinatal asphyxia is an important cause of morbidity and mortality
in the neonatal period, accounting for 20-30% of neonatal mortality. A
substantial proportion (estimated at 26%) of the 1 million annual intrapartum
stillbirths result from asphyxia. Probably higher than the mortality is the
plethora of morbidity associated with asphyxia, especially long term neuro
developmental problems including cerebral palsy.The real burden of perinatal
asphyxia is difficult to establish because of paucity of information from the
rural communities where the majority of neonatal morbidity and deaths occur.
Extended Apgar scores and HIE grade have been identified as predictive tools in
prognosticating asphyxia, however HIE staging require a certain level of medical
expertise which is not widely available. AIM: To determine the incidence of
asphyxia, the mortality rate and factors associated with mortality in Irrua
Specialist Hospital. METHOD: It was a descriptive, retrospective study of
neonates admitted into the special care baby unit (SCBU) between October 2013 and
September 2014 with diagnosis of perinatal asphyxia. Data was obtained from
babies' and mother's case notes. The outcome was classified as survived or died.
RESULTS: Perinatal asphyxia accounted for 45 out of 347 (13%) of admissions
within the review period. The mean gestational age and birth weight of the
subjects were 39.2+/-2.2 weeks and 3020+/-520 grams respectively. The mortality
rate was 31.1% and the factors significantly associated with mortality include
lack of antenatal care and HIE stage III. CONCLUSION: The burden of perinatal
asphyxia in Irrua Specialist Hospital is comparable to figures from similar
settings in the developing world. Lack of antenatal care and HIE stage III are
associated with mortality. Continuous efforts should be made to improve the
uptake of antenatal care and high risk pregnancies should be delivered in centres
with facilities for neonatal care.
PMID- 29966209
TI - Inflammation and rehabilitation outcomes in patients with nontraumatic
intracranial haemorrhage.
AB - BACKGROUND: Systemic inflammation and its impact on rehabilitation for patients
with non-traumatic haemorrhagic injury (HBI) sequelae has not yet been adequately
documented. OBJECTIVE AND METHODS: We therefore considered 31 patients with HBI,
to determine the serum levels of inflammatory markers (C-Reactive Protein, CRP
and or interleukine-6, IL-6) to establish their impact on functional status
(Functional Independence Measure, FIM: 18 indicating the worst performance and
126, a normal score). RESULTS: The results showed an inflammation prevalence (CRP
>0.5 mg/dl and/or IL 6 >7 pg/ml) of 74.2% at admission to Rehab. FIM reduction
was more pronounced in inflamed compared to non-inflamed subjects (p < 0.05) and
significantly correlated with blood variables sensitive to inflammation, such as
alpha 1 globulin (r = - 0.565) and neutrophil/ lymphocyte ratio (r = - 0.52), CRP
(r = - 0.365). At discharge from Rehab, the inflammation rate diminished.
Inflamed patients showed similar gains in FIM score as their controls. In the
entire population, the FIM gain was significantly associated with a gain in serum
albumin, only (r = +0.56). CONCLUSIONS: We conclude that systemic inflammation is
prevalent in HBI patients and contributes to reduce patient functional status.
However, during the Rehab stage, inflammation does not hinder the improvement
rate of functional capacity.
PMID- 29966210
TI - Simplified surgical approach to improve surgical outcomes in the center with a
small volume of acute type A aortic dissection surgery.
AB - BACKGROUND: Despite recent advances in surgical techniques and perioperative
management, the surgical mortality of acute type A aortic dissection remains
high. OBJECTIVE: In a hospital with few acute type A aortic dissection
operations, we retrospectively investigated whether simplified surgical approach
could obtain proper surgical outcomes. METHODS: Between October 2007 and December
2016, we performed emergency surgery in 99 patients who had acute type A aortic
dissection, including replacement of the hemi-arch in 62 patients (63%) and total
arch in 32 patients (32%) and aortic root surgery in 7 patients (7%). Surgical
strategy has been simplified over time. RESULTS: We performed right axillary
artery perfusion in 61 patients (62%) and antegrade cerebral perfusion in 78
patients (79%). During the last 3 years, in-hospital mortality was decreased to
4% (2/47). Preoperative unresolved shock was an independent predictor of hospital
death. Although the patients with total arch replacement or aortic root surgery
had a mean significantly long cardiopulmonary bypass or circulatory arrest time,
in-hospital mortality or neurologic complications was not increased. CONCLUSIONS:
Simplified surgical approach could provide a reasonable surgical outcome in acute
type A aortic dissection surgery in a center with a small volume of acute aortic
dissection surgery.
PMID- 29966211
TI - Effect of different speeds and ground environment of squat exercises on lower
limb muscle activation and balance ability.
AB - BACKGROUND: Squat is the most important exercise for the strengthening of the
lower limb muscles. The muscle contraction speed and type affect the muscle
activation, strength, and power. OBJECTIVE: This study aimed to investigate the
influence of two different speeds of squat exercise on the activation and balance
of the lower limb muscles. METHODS: Thirty-eight healthy adults randomly
performed squat exercises at different speeds and in different ground
environments, 3 times per week for 4 weeks. The participants' lower limb muscle
activation and balance ability were evaluated before and after the training.
RESULTS: There was a significant difference in muscle activation between the
squats in terms of speed (fast, moderate, and slow squat) (p< 0.05). After the
training periods, there was a significant difference in the rectus femoris (RF)
and biceps femoris (BF) of the groups that performed the fast squat (p< 0.05).
There was significant difference between the pre- and post-static balance test in
the group that performed fast squats on an unstable surface (p< 0.05). After the
training periods, the stability index with eyes open values, which is static
balance, showed a significant difference among the groups after 4 weeks (p<
0.05). The groups that performed fast squat showed a significant difference
between the pre- and post-dynamic Y balance test (p< 0.05). CONCLUSIONS: For
optimal performance and effect of selected squat exercises, the speed and ground
environment should be taken into consideration.
PMID- 29966212
TI - Optimization of drilling parameters for thermal bone necrosis prevention.
AB - BACKGROUND: Bone drilling is a mandatory process in orthopedic surgery to fix the
fractured bones. Excessive heat is generated due to the shear deformation of bone
and friction energy during the drilling process. OBJECTIVE: This paper is carried
out to optimize the bone drilling parameters to prevent thermal bone necrosis.
The main contribution of this work is instead of only consider the influence of
rotational speed and feed rate, the effect of tool diameter and drilling hole
depth are also incorporated for optimization study. METHODS: Response surface
methodology (RSM) was used to develop a temperature prediction model. Drilling
experiments were performed using finite element software DEFORM-3D. Analysis of
variance (ANOVA) was conducted to investigate the drilling parameters' effect.
Desirability function in RSM was used to determine the optimum combination of
drilling parameters. RESULTS: Results indicated that one applicable combination
of drilling parameters could increase the bone temperature by less than 0.03%. To
avoid thermal bone necrosis, eight reasonable combinations of drilling parameters
were proposed. 3.3?C residuals between in-vitro experiments and predicted values
were demonstrated. CONCLUSIONS: It is envisaged that finite element simulation
with RSM can simplify tedious experimental works and useful in the clinical
application to avoid bone necrosis.
PMID- 29966213
TI - Economic aspects and managerial implications of the new technology in the
treatment of low back pain.
AB - BACKGROUND: The Human Body Posturizer (HPB), an innovative therapeutic tool able
to correct postural changes dynamically, fits perfectly in this framework.
OBJECTIVE: The aim of this paper is to consider the potential economic benefits
of using the Human Body Posturizer both in terms of direct and indirect cost
reduction in one year. METHODS: This study was carried out using an estimation
method in order to investigate the possible economic impact related to the
adoption of the HBP in subjects with low back pain as an attempt to quantify the
costs (direct and indirect) generated at different levels of the path
therapeutic. RESULTS: The use of therapy with HBP would generate a saving of ?
971.40/year in case of sub-acute LBP and amounted to ? 2,922.90/year in case of
chronic low back pain. CONCLUSION: This paper provides guidance on the potential
economic benefits resulting from the adoption of the Human Body Posturizer as an
innovative therapeutic approach by the Italian Health System.
PMID- 29966214
TI - Effects of Toe Spreader on Plantar pressure and Gait in chronic stroke patients.
AB - BACKGROUND: The feet make the initial contact with the ground when walking and
critically control both posture and gait. Claw toe, a structural change in the
foot that may develop after stroke, triggers functional changes affecting both
the lower limbs and balance. OBJECTIVE: We analyzed the effects of a toe spreader
on foot pressure and gait in chronic stroke patients. METHODS: We enrolled 25
stroke patients. We used Gaitview AFA-50 and GAITRite instruments to measure
plantar pressure distribution and gait with and without a tow spreader. RESULTS:
The average and rear foot pressures increased somewhat when a toe spreader was
used. However, the differences were not significant in post hoc tests. In terms
of gait, all variables significantly improved when the toe spreader was used.
CONCLUSIONS: A toe spreader may improve overall gait and spatiotemporal gait
parameters in chronic stroke patients.
PMID- 29966215
TI - A scoping review of the incentives for a prolonged work life after pensionable
age and the importance of "bridge employment".
AB - BACKGROUND: With a growing share of older people in almost every population,
discussions are being held worldwide about how to guarantee welfare in the
immediate future. Different solutions are suggested, but in this article the
focus is on the need to keep older employees active in the labor market for a
prolonged time. OBJECTIVE: The aim was to find out and describe the incentives at
three system levels for older people 1) wanting, 2) being able, and 3) being
allowed to work. MATERIAL: The literature search embraced articles from the
databases Scopus, PsycInfo, Cinahl, AgeLine and Business Source Premier, from May
2004 until May 2016. After the removal of 506 duplicates, the selection and
analysis started with the 1331 articles that met the search criteria. Of these,
58 articles corresponded with the research questions. METHOD: The design was a
'scoping review' of the research area bridge employment and prolonged work life.
RESULTS: The results show that most investigations are conducted on individual
level predictors, research on organizational-level predictors is more scattered,
and societal-level predictor information is scarce. CONCLUSIONS: Attitudes and
behavior according to a prolonged work life could be summarized as dependent on
good health, a financial gain in combination with flexible alternative working
conditions.
PMID- 29966216
TI - Decent work, work motivation and psychological capital: An empirical research.
AB - BACKGROUND: The Decent Work (DW) concept, proposed by the International Labour
Organization, can be enriched by the contributions of a Work, Organizational and
Personnel Psychology (WOPP) perspective. Namely, it would be important to relate
DW perceptions to the main concepts in the WOPP realm. Understanding these
relations would expand our knowledge of the nomological network of the DW concept
and of its practical implications. OBJECTIVE: To analyze the relationships
between DW, work motivation and psychological capital among knowledge workers in
Portugal and Brazil. METHODS: The Decent Work Questionnaire (DWQ), a previously
validated measure of 7 dimensions of DW from a WOPP perspective, the
Multidimensional Work Motivation Scale (MWMS), and the Psychological Capital
Questionnaire (PCQ) were administered to 2912 knowledge workers. Relations among
concepts were analyzed by canonical correlation analyses and linear regression.
RESULTS: The DW dimension Fulfilling and Productive Work was positively
associated with intrinsic and identified work motivation, and negatively with
amotivation. A second significant canonical variate related (negatively) Social
Protection (DW dimension) to extrinsic material work motivation. Results from
regression analysis support the idea that DW promotes psychological capital.
CONCLUSIONS: Results suggest that DW is an important predictor of work motivation
and psychological capital. Practical implications for human resources management
are presented.
PMID- 29966217
TI - From the Editor.
PMID- 29966218
TI - Effect of Ni Content on Microstructure and Characterization of Cu-Ni-Sn Alloys.
AB - Cu-xNi-5Sn (wt %) alloys with a different Ni content were prepared by a powder
metallurgy method. The effect of Ni content on the hardness and yield strength of
Cu-xNi-5Sn (wt %) alloys was investigated. The microstructure, composition, and
morphology of Cu-xNi-5Sn (wt %) alloys were observed by X-ray diffraction (XRD),
scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), and
cold field emission scanning electron microscope (FESEM), respectively. Results
indicate that the hardness and yield strength firstly increase and then decrease
with the increase of Ni content and reach up to a maximum when Ni content is 12.5
wt %. Furthermore, the formation of the sandwich structure and needle-like phase
is found in the grain, the grain boundary and intragranular precipitates are rich
in both the Ni and Sn phase. The formation of the inerratic and suitable lamellar
precipitates of sandwich structure and needle-like phase can be responsible for
the good mechanical properties of the Cu-12.5Ni-5Sn alloy after aging treatment.
The sandwich structure and need-like phase that were observed by FESEM can
contribute to clarify the morphology of Cu-Ni-Sn alloys.
PMID- 29966219
TI - Cerebral Dopamine Neurotrophic Factor (CDNF) Has Neuroprotective Effects against
Cerebral Ischemia That May Occur through the Endoplasmic Reticulum Stress
Pathway.
AB - Cerebral dopamine neurotrophic factor (CDNF), previously known as the conserved
dopamine neurotrophic factor, belongs to the evolutionarily conserved
CDNF/mesencephalic astrocyte-derived neurotrophic factor MANF family of
neurotrophic factors that demonstrate neurotrophic activities in dopaminergic
neurons. The function of CDNF during brain ischemia is still not known. MANF is
identified as an endoplasmic reticulum (ER) stress protein; however, the role of
CDNF in ER stress remains to be fully elucidated. Here, we test the
neuroprotective effect of CDNF on middle cerebral artery occlusion (MCAO) rats
and neurons and astrocytes treated with oxygen-glucose depletion (OGD). We also
investigate the expression of CDNF in cerebral ischemia and in primary neurons
treated with ER stress-inducing agents. Our results show that CDNF can
significantly reduce infarct volume, reduce apoptotic cells and improve motor
function in MCAO rats, while CDNF can increase the cell viability of neurons and
astrocytes treated by OGD. The expression of CDNF was upregulated in the peri
infarct tissue at 2 h of ischemia/24 h reperfusion. ER stress inducer can induce
CDNF expression in primary cultured neurons. Our data indicate that CDNF has
neuroprotective effects on cerebral ischemia and the OGD cell model and the
protective mechanism of CDNF may occur through ER stress pathways.
PMID- 29966220
TI - Nanocomposite Zinc Oxide-Chitosan Coatings on Polyethylene Films for Extending
Storage Life of Okra (Abelmoschus esculentus).
AB - Efficiency of nanocomposite zinc oxide-chitosan antimicrobial polyethylene
packaging films for the preservation of quality of vegetables was studied using
okra Abelmoschus esculentus. Low density polyethylene films (LDPE) coated with
chitosan-ZnO nanocomposites were used for packaging of okra samples stored at
room temperature (25 °C). Compared to the control sample (no coating), the
total bacterial concentrations in the case of chitosan and nanocomposite coatings
were reduced by 53% and 63%, respectively. The nanocomposite coating showed a 2
fold reduction in total fungal concentrations in comparison to the chitosan
treated samples. Results demonstrate the effectiveness of the nanocomposite
coatings for the reduction of fungal and bacterial growth in the okra samples
after 12 storage days. The nanocomposite coatings did not affect the quality
attributes of the okra, such as pH, total soluble solids, moisture content, and
weight loss. This work demonstrates that the chitosan-ZnO nanocomposite coatings
not only maintains the quality of the packed okra but also retards microbial and
fungal growth. Thus, chitosan-ZnO nanocomposite coating can be used as a
potential coating material for active food packaging applications.
PMID- 29966222
TI - The Role of Fc Gamma Receptors in Broad Protection against Influenza Viruses.
AB - Recent studies have revealed multiple roles for Fc gamma receptors (FcγRs)
in broad immunity against influenza viruses. Activating FcγR pathways can
be harnessed to confer protection mediated by non-neutralizing anti-HA IgGs and
to increase the potency of broadly neutralizing anti-HA IgGs and of anti-NA IgGs.
Separate FcγR pathways can be targeted to enhance the breadth of antibody
responses elicited by seasonal influenza virus vaccines. Here, we review the
current understanding of FcγR pathways in broad influenza immunity and
suggest mechanisms to bypass FcγR signaling heterogeneity among people that
arises from distinctions in structural repertoires of IgG Fc domains.
PMID- 29966221
TI - Roles of the Glucocorticoid and Mineralocorticoid Receptors in Skin
Pathophysiology.
AB - The nuclear hormone receptor (NR) superfamily comprises approximately 50
evolutionarily conserved proteins that play major roles in gene regulation by
prototypically acting as ligand-dependent transcription factors. Besides their
central role in physiology, NRs have been largely used as therapeutic drug
targets in many chronic inflammatory conditions and derivatives of their specific
ligands, alone or in combination, are frequently prescribed for the treatment of
skin diseases. In particular, glucocorticoids (GCs) are the most commonly used
compounds for treating prevalent skin diseases such as psoriasis due to their
anti-proliferative and anti-inflammatory actions. However, and despite their
therapeutic efficacy, the long-term use of GCs is limited because of the
cutaneous adverse effects including atrophy, delayed wound healing, and increased
susceptibility to stress and infections. The GC receptor (GR/NR3C1) and the
mineralocorticoid receptor (MR/NR3C2) are members of the NR subclass NR3C that
are highly related, both structurally and functionally. While the GR is
ubiquitously expressed and is almost exclusively activated by GCs; an MR has a
more restricted tissue expression pattern and can bind GCs and the
mineralocorticoid aldosterone with similar high affinity. As these receptors
share 95% identity in their DNA binding domains; both can recognize the same
hormone response elements; theoretically resulting in transcriptional regulation
of the same target genes. However, a major mechanism for specific activation of
GRs and/or MRs is at the pre-receptor level by modulating the local availability
of active GCs. Furthermore, the selective interactions of each receptor with
spatio-temporally regulated transcription factors and co-regulators are crucial
for the final transcriptional outcome. While there are abundant genome wide
studies identifying GR transcriptional targets in a variety of tissue and cell
types; including keratinocytes; the data for MR is more limited thus far. Our
group and others have studied the role of GRs and MRs in skin development and
disease by generating and characterizing mouse and cellular models with gain- and
loss-of-function for each receptor. Both NRs are required for skin barrier
competence during mouse development and also play a role in adult skin
homeostasis. Moreover, the combined loss of epidermal GRs and MRs caused a more
severe skin phenotype relative to single knock-outs (KOs) in developing skin and
in acute inflammation and psoriasis, indicating that these corticosteroid
receptors play cooperative roles. Understanding GR- and MR-mediated signaling in
skin should contribute to deciphering their tissue-specific relative roles and
ultimately help to improve GC-based therapies.
PMID- 29966223
TI - Surface Nanostructuring of Parylene-C Coatings for Blood Contacting Implants.
AB - This paper investigates the effects on the blood compatibility of surface
nanostructuring of Parylene-C coating. The proposed technique, based on the
consecutive use of O2 and SF6 plasma, alters the surface roughness and enhances
the intrinsic hydrophobicity of Parylene-C. The degree of hydrophobicity of the
prepared surface can be precisely controlled by opportunely adjusting the plasma
exposure times. Static contact angle measurements, performed on treated Parylene
C, showed a maximum contact angle of 158°. The nanostructured Parylene-C
retained its hydrophobicity up to 45 days, when stored in a dry environment.
Storing the samples in a body-mimicking solution caused the contact angle to
progressively decrease. However, at the end of the measurement, the plasma
treated surfaces still exhibited a higher hydrophobicity than the untreated
counterparts. The proposed treatment improved the performance of the polymer as a
water diffusion barrier in a body simulating environment. Modifying the
nanotopography of the polymer influences the adsorption of different blood plasma
proteins. The adsorption of albumin—a platelet adhesion inhibitor—and
of fibrinogen—a platelet adhesion promoter—was studied by
fluorescence microscopy. The adsorption capacity increased monotonically with
increasing hydrophobicity for both studied proteins. The effect on albumin
adsorption was considerably higher than on fibrinogen. Study of the proteins
simultaneous adsorption showed that the albumin to fibrinogen adsorbed ratio
increases with substrate hydrophobicity, suggesting lower thrombogenicity of the
nanostructured surfaces. Animal experiments proved that the treated surfaces did
not trigger any blood clot or thrombus formation when directly exposed to the
arterial blood flow. The findings above, together with the exceptional mechanical
and insulation properties of Parylene-C, support its use for packaging implants
chronically exposed to the blood flow.
PMID- 29966224
TI - Spatial Memory Dysfunction Induced by Vitamin C Deficiency Is Associated with
Changes in Monoaminergic Neurotransmitters and Aberrant Synapse Formation.
AB - Vitamin C (vitC) is important in the developing brain, acting both as an
essential antioxidant and as co-factor in the synthesis and metabolism of
monoaminergic neurotransmitters. In guinea pigs, vitC deficiency results in
increased oxidative stress, reduced hippocampal volume and neuronal numbers, and
deficits in spatial memory. This study investigated the effects of 8 weeks of
either sufficient (923 mg vitC/kg feed) or deficient (100 mg vitC/kg feed) levels
of dietary vitC on hippocampal monoaminergic neurotransmitters and markers of
synapse formation in young guinea pigs with spatial memory deficits. Western
blotting and high performance liquid chromatography (HPLC) were used to quantify
the selected markers. VitC deficiency resulted in significantly reduced protein
levels of synaptophysin (p = 0.016) and a decrease in 5-hydroxyindoleacetic
acid/5-hydroxytryptamine ratio (p = 0.0093). Protein expression of the N-methyl-d
aspartate receptor subunit 1 and monoamine oxidase A were reduced, albeit not
reaching statistical significance (p = 0.0898 and p = 0.067, respectively). Our
findings suggest that vitC deficiency induced spatial memory deficits might be
mediated by impairments in neurotransmission and synaptic development.
PMID- 29966225
TI - New Bisabosquals from Stachybotrys sp. PH30583 Elicited on Solid Media.
AB - Stachybotrys sp. PH30583 cultured in liquid medium only led to one structure type
of novel isochroman dimers. Using the one strain-many compounds strategy, the
reinvestigation of the metabolites from Stachybotrys sp. PH30583 cultured in rice
solid medium led to the isolation of four triprenyl phenols, including two new
bisabosquals and two known phenylspirodrimanes. Nitrobisabosquals A and B (1 and
2) are the first case of pyrrolidone-bisabosquals reported in literature. Totally
different compounds were isolated using rice solid medium, compared with those
isolated using liquid medium, so that rice solid medium presents a key factor in
the production of triprenyl phenols. Compound 1 exhibited cytotoxicity against
tumor cells, A-549, HL-60, MCF-7 SMMC-7721, and SW480, as well as weak
anticoagulant activity with activated partial thromboplastin time (APTT) of 32.1
+/- 0.17 s (p < 0.05 vs. Con.) at a concentration of 5 mM. Triprenyl phenol
metabolites could be used as chemotaxonomic markers for Stachybotrys.
PMID- 29966226
TI - Characterization of Bacterial Communities and Their Antibiotic Resistance
Profiles in Wastewaters Obtained from Pharmaceutical Facilities in Lagos and Ogun
States, Nigeria.
AB - In Nigeria, pharmaceutical wastewaters are routinely disseminated in river
waters; this could be associated with public health risk to humans and animals.
In this study, we characterized antibiotic resistant bacteria (ARB) and their
antibiotic resistance profile as well as screening for sul1 and sul2 genes in
pharmaceutical wastewater effluents. Bacterial composition of the wastewater
sources was isolated on non-selective media and characterized by the polymerase
chain reaction (PCR) amplification of the 16S rRNA genes, with subsequent
grouping using restriction fragment length polymorphism (RFLP) and sequencing.
The antibiotics sensitivity profiles were investigated using the standard disk
diffusion plate method and the minimum inhibitory concentrations (MICs) of
selected antibiotics on the bacterial isolates. A total of 254 bacterial strains
were isolated, and majority of the isolates were identified as Acinetobacter sp.,
Klebsiella pneumonia, Proteus mirabilis, Enterobacter sp. and Bacillus sp. A
total of 218 (85.8%) of the bacterial isolates were multidrug resistant. High
MICs values were observed for all antibiotics used in the study. The result
showed that 31.7%, 21.7% and 43.3% of the bacterial isolates harbored sul1, sul2,
and Intl1 genes, respectively. Pharmaceuticals wastewaters are potential
reservoirs of ARBs which may harbor resistance genes with possible risk to public
health.
PMID- 29966228
TI - Suicide Stigma among Medical Students in Puerto Rico.
AB - Suicide is a global public health issue and the 10th leading cause of death,
regardless of age, in the U.S. Puerto Ricans are U.S. citizens with one of the
highest rates of suicide ideation and attempts (SIA) among all Latino sub-groups.
Research has found that stigma is a risk factor for SIA. Medical students are an
important group to target as they engage in routine clinical interactions with
potential suicide victims, playing an important role in suicide prevention
efforts. However, these efforts may be hampered by suicide stigma. The purpose of
this study is to examine the correlates of suicide stigma in a sample of medical
students in Puerto Rico. We implement an exploratory cross-sectional design using
quantitative techniques. A total of 123 medical students participate in the
study. Bivariate analyses suggest that gender is significantly correlated to
suicide stigma (p < 0.05). Hierarchical regression analysis suggests that suicide
literacy (β = −0.196, p < 0.05) and emotional reaction to suicide
(β = 0.212, p < 0.05) predict suicide stigma. Although preliminary, these
findings echo previous research regarding the importance of literacy and
emotional reaction in the stigmatization process. Future research may develop
intervention strategies aimed at reducing suicide stigma among medical students.
PMID- 29966229
TI - Effectiveness of Essence of Chicken on Cognitive Function Improvement: A
Randomized Controlled Clinical Trial.
AB - High-quality, adequately-powered clinical trials investigating the effect of
Essence of Chicken (EC) on cognitive function are lacking. We conducted a
randomized, double-blind, placebo-controlled clinical trial on healthy adult
volunteers to determine the effect of EC on short-term memory, working memory,
and selective and sustained attention. As a secondary objective, we evaluated
baseline stress as a modifying factor by including treatment, stress and visit as
main effects in a three-way ANOVA model. Cognitive function was evaluated at
baseline, and Days 7 and 14. Data from 235 participants were analyzed on a per
protocol basis. The three-way interaction effect was significant (p = 0.020) in
Digit Span Forward and further analyses showed EC improved test performance in
moderate (p = 0.041) and severe stress (p = 0.065) but not in normal and mild
stress subgroups. In Digit Span Backward, EC group showed greater improvement
compared to placebo (p = 0.028), with 0.60 digits (8.50% improvement from
baseline) more recalled on Day 7. No treatment or interaction effects were
statistically significant in selective and sustained attention tests. Our
findings support EC’s effect in improving mental processes used in working
memory among healthy adults and short-term memory among healthy adults
experiencing stress in daily life.
PMID- 29966227
TI - The Involvement of PPARs in the Peculiar Energetic Metabolism of Tumor Cells.
AB - Energy homeostasis is crucial for cell fate, since all cellular activities are
strongly dependent on the balance between catabolic and anabolic pathways. In
particular, the modulation of metabolic and energetic pathways in cancer cells
has been discussed in some reports, but subsequently has been neglected for a
long time. Meanwhile, over the past 20 years, a recovery of the study regarding
cancer metabolism has led to an increasing consideration of metabolic alterations
in tumors. Cancer cells must adapt their metabolism to meet their energetic and
biosynthetic demands, which are associated with the rapid growth of the primary
tumor and colonization of distinct metastatic sites. Cancer cells are largely
dependent on aerobic glycolysis for their energy production, but are also
associated with increased fatty acid synthesis and increased rates of glutamine
consumption. In fact, emerging evidence has shown that therapeutic resistance to
cancer treatment may arise from the deregulation of glucose metabolism, fatty
acid synthesis, and glutamine consumption. Cancer cells exhibit a series of
metabolic alterations induced by mutations that lead to a gain-of-function of
oncogenes, and a loss-of-function of tumor suppressor genes, including increased
glucose consumption, reduced mitochondrial respiration, an increase of reactive
oxygen species, and cell death resistance; all of these are responsible for
cancer progression. Cholesterol metabolism is also altered in cancer cells and
supports uncontrolled cell growth. In this context, we discuss the roles of
peroxisome proliferator-activated receptors (PPARs), which are master regulators
of cellular energetic metabolism in the deregulation of the energetic
homeostasis, which is observed in cancer. We highlight the different roles of
PPAR isotypes and the differential control of their transcription in various
cancer cells.
PMID- 29966230
TI - Investigation of Three-Dimensional Microstructure of Tricalcium Silicate (C3S) by
Electron Microscopy.
AB - A serial block-face scanning electron microscopy (SBFSEM) system, composed of a
scanning electron microscope (SEM) and an ultra-microtome installed within the
SEM vacuum chamber, has been used to characterize the three-dimensional (3D)
microstructure of tricalcium silicate (C3S) grains embedded in epoxy resin. A
selection of C3S grains were segmented and rendered with 3D-image processing
software, which allowed the C3S grains to be clearly visualized and enabled
statistically quantitative analysis. The results show that about 5% of the C3S
grains have volumes larger than 1 μm3 and the average volume of the grains is
25 μm3. Pores can also be clearly seen in the biggest C3S grain, the volume of
which is 3.6 × 104 μm3, and the mean volume and total volume of all the
pores within this grain are 4.8 μm3 and 3.0 × 103 μm3, respectively.
The reported work provides a new approach for the characterization of the 3D
spatial structure of raw C3S materials, and the resulting 3D structure of the raw
C3S is important for further systematic research on the relationships between the
spatial microstructure and the hydration kinetics of C3S and other cement
minerals.
PMID- 29966231
TI - Adaptive Noise Reduction Algorithm to Improve R Peak Detection in ECG Measured by
Capacitive ECG Sensors.
AB - Electrocardiograms (ECGs) can be conveniently obtained using capacitive ECG
sensors. However, motion noise in measured ECGs can degrade R peak detection. To
reduce noise, properties of reference signal and ECG measured by the sensors are
analyzed and a new method of active noise cancellation (ANC) is proposed in this
study. In the proposed algorithm, the original ECG signal at QRS interval is
regarded as impulsive noise because the adaptive filter updates its weight as if
impulsive noise is added. As the proposed algorithm does not affect impulsive
noise, the original signal is not reduced during ANC. Therefore, the proposed
algorithm can conserve the power of the original signal within the QRS interval
and reduce only the power of noise at other intervals. The proposed algorithm was
verified through comparisons with recent research using data from both indoor and
outdoor experiments. The proposed algorithm will benefit a noise reduction of
noisy biomedical signal measured from sensors.
PMID- 29966232
TI - An Enhanced Paradigm for Cognitive Cooperation Networks: Two-to-One Energy and
Spectrum Dual-Cooperation.
AB - In this paper, two-to-one energy and spectrum dual-cooperation (ESDC) is
investigated for cognitive cooperation networks. Specifically, the energy and
spectrum of two primary users (PUs) are both transferred or authorized to one
multi-antenna secondary user (SU) in exchange for its aid in the signal relaying
to guarantee the successful data transmission, whilst the SU, which originally
owns no spectrum access privilege and limited energy storage, is also able to
concurrently transmit its own data through spatial multiplexing. Moreover,
network-coding is also adopted to further compress the data size and hence reduce
the power consumption at SU. The formulated problem for the aforementioned two-to
one ESDC model is non-convex and intractable to solve directly. To solve the
problem effectively, the Lagrangian dual methods plus fixed-point iteration
methods and semidefinite relation methods are employed, and the optimal solution
could be achieved through iterative optimization. Simulation results show that,
compared with the traditional spectrum-only cooperation, the proposed two-to-one
ESDC paradigms can greatly improve the successful transmission probability for
PUs and achievable transmission rate for SU. Meanwhile, the proposed two-to-one
dual-cooperation modes are significantly superior to the one-to-one cooperation
mode, in terms of spectrum efficiency and energy efficiency.
PMID- 29966233
TI - A Review of the Recent Advances Made with SIRT6 and its Implications on Aging
Related Processes, Major Human Diseases, and Possible Therapeutic Targets.
AB - Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide+ (NAD+) dependent enzyme
and stress response protein that has sparked the curiosity of many researchers in
different branches of the biomedical sciences. A unique member of the known
Sirtuin family, SIRT6 has several different functions in multiple different
molecular pathways related to DNA repair, glycolysis, gluconeogenesis,
tumorigenesis, neurodegeneration, cardiac hypertrophic responses, and more. Only
in recent times, however, did the potential usefulness of SIRT6 come to light as
we learned more about its biochemical activity, regulation, biological roles, and
structure Frye (2000). Even until very recently, SIRT6 was known more for
chromatin signaling but, being a nascent topic of study, more information has
been ascertained and its potential involvement in major human diseases including
diabetes, cancer, neurodegenerative diseases, and heart disease. It is pivotal to
explore the mechanistic workings of SIRT6 since future research may hold the key
to engendering strategies involving SIRT6 that may have significant implications
for human health and expand upon possible treatment options. In this review, we
are primarily concerned with exploring the latest advances in understanding SIRT6
and how it can alter the course of several life-threatening diseases such as
processes related to aging, cancer, neurodegenerative diseases, heart disease,
and diabetes (SIRT6 has also shown to be involved in liver disease, inflammation,
and bone-related issues) and any recent promising pharmacological investigations
or potential therapeutics that are of interest.
PMID- 29966234
TI - Physicochemical Properties and Biocompatibility Evaluation of Collagen from the
Skin of Giant Croaker (Nibea japonica).
AB - Collagen and collagen peptides are widely used as cosmetic ingredients. In the
present study, acid-solubilized collagen (ASC) and pepsin-solubilized collagen
(PSC) were extracted from giant croaker (Nibea japonica) skin. The proline
hydroxylation rates of ASC and PSC were 38.1% and 39.3%. The denaturation
temperatures (Td) were approximately 34.5 °C for both ASC and PSC. The
results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
and fourier transform infrared spetroscopy (FTIR) demonstrated that ASC and PSC
were mainly type I collagen. Furthermore, As, Pb and Hg contents in the extracted
collagen were lower than the national standards of China. In addition, collagen
had good moisture absorption and retention properties when compared to glycerol.
The collagen was also not cytotoxic to NIH-3T3 fibroblast cells, indicating that
Nibea japonica skin collagen can be utilized in cosmetic applications.
PMID- 29966235
TI - An Innovative Diagnostic Film for Structural Health Monitoring of Metallic and
Composite Structures.
AB - A novel lightweight diagnostic film with sensors/actuators and a multiple-path
wiring option using inkjet printing was developed. The diagnostic film allows for
systematic, accurate, and repeatable sensor placement. Furthermore, the film is
highly flexible and adaptable for placement on complex configurations. The film
can be attached to the surface of the structure through a uniform secondary
boundary procedure or embedded within the composite layup during curing. The
surface-mounted film can simply be peeled off for repair or replacement without
scratching or damaging the part. The film offers significant weight reduction
compared to other available technologies. A set of extreme temperature, altitude,
and vibration environment test profiles were carried out following the Radio
Technical Commission for Aeronautics (RTCA) DO-160 document to assess the
durability and performance of the diagnostic film for onboard application. The
diagnostic film was shown to be durable and reliable in withstanding the variable
operational and harsh environmental conditions of tests representing the
conditions of regional aircraft.
PMID- 29966237
TI - How Green Are the Streets Within the Sixth Ring Road of Beijing? An Analysis
Based on Tencent Street View Pictures and the Green View Index.
AB - Street greenery, an important urban landscape component, is closely related to
people’s physical and mental health. This study employs the green view
index (GVI) as a quantitative indicator to evaluate visual greenery from a
pedestrian’s perspective and uses an image segmentation method to calculate
the quantity of visual greenery from Tencent street view pictures. This article
aims to quantify street greenery in the area within the sixth ring road in
Beijing, analyse the relations between road parameters and the GVI, and compare
the visual greenery of different road types. The authors find that (1) the
average GVI value in the study area is low, with low-value clusters inside the
third ring road and high-value clusters outside; (2) wider minor roads tend to
have higher GVI values than motorways, major roads and provincial roads; and (3)
longer roads, except expressways, tend to have higher GVI values. This case study
demonstrates that the GVI can effectively represent the quantity of visual
greenery along roads. The authors’ methods can be employed to compare
street-level visual greenery among different areas or road types and to support
urban green space planning and management.
PMID- 29966236
TI - Dietary Intake and Food Sources of Niacin, Riboflavin, Thiamin and Vitamin B6 in
a Representative Sample of the Spanish Population. The Anthropometry, Intake, and
Energy Balance in Spain (ANIBES) Study ?.
AB - Thiamin, riboflavin, niacin, and vitamin B6 are essential micronutrients that are
mainly involved in energy metabolism; they may prevent the occurrence of
developmental abnormalities and chronic degenerative and neoplastic diseases. The
aim was to analyze dietary intake and food sources of those four nutrients in
subjects (n = 2009) aged 9-75 years old from the Spanish ANIBES (Anthropometry,
Intake, and Energy Balance in Spain) study. Dietary data were collected by means
of a validated, photo-based three-day dietary food record. Underreporting was
analysed according to the European Food and Safety Authority (EFSA, Parma, Italy)
protocol. Mean (max-min) reported intake for the whole population of thiamin was
1.17 +/- 0.02 mg/day, (0.30-3.44 mg/day), riboflavin 1.44 +/- 0.02 mg/day, (0.37
3.54 mg/day), niacin 29.1 +/- 0.2 mg/day (6.7-109 mg/day), and vitamin B6 1.54 +/
0.01 mg/day (0.28-9.30 mg/day). The main sources of intake for thiamin, niacin,
and vitamin B6 were meat and meat products, and for riboflavin were milk and
dairy products. An elevated percentage of the Spanish ANIBES population meets the
EFSA recommended intakes for thiamin (71.2%), riboflavin (72.0%), niacin (99.0%),
and vitamin B6 (77.2%).
PMID- 29966238
TI - Interferon Crevicular Fluid Profile and Correlation with Periodontal Disease and
Wound Healing: A Systemic Review of Recent Data.
AB - The purpose of the present study was to see if there is a correlation between the
effect of interferons in crevicular fluid and periodontitis, evaluating
literature. Interferon gamma (IFN-γ) is an immunoregulatory cytokine that,
when activated by its receptor, plays an important role in the activation of
inflammatory processes, which are the basis of periodontal disease. Stem cells in
the periodontal ligament, like stem cells from other tissues, have
immunomodulatory capacity and are regulated by some cytokines such as interferon
γ (IFN-γ). The study searched MEDLINE databases from 2008 to 2018.
Clinical human in vitro and in vivo studies had reported a correlation between
interferon and periodontitis. The initial search obtained 359 citations. After
screening and determination of eligibility, nine articles were included in the
review. Significant (p < 0.05) increases in IFN-γ gene expression were
observed in some studies in the chronic periodontitis group. In some cases it was
suggested that molecular mechanisms underlie the possible roles of IFN-γ in
the inhibition of osteoclastogenesis. Neopterin belongs to the chemical group
known as pteridines. It is synthesised by human macrophages upon stimulation with
the interferon-gamma. Neopterin concentrations in body fluids are high in the
case of infections, immune diseases or graft rejection. In the chronic
periodontitis group, this marker is significantly higher. These studies
underlined the clinical evidence between interferons in the crevicular fluid and
inflammatory response of periodontitis. However, there is a lack of scientific
evidence that could lead the clinician to an interferon-modulated therapy because
of periodontitis.
PMID- 29966239
TI - Enhanced Dielectric and Mechanical Properties of Ternary Composites via
Plasticizer-Induced Dense Interfaces.
AB - High overall performance, including high dielectric constant, low loss, high
breakdown strength, fine flexibility, and strong tensile properties, is difficult
to achieve simultaneously in polymer nanocomposites. In our prior work, we
modified the surfaces of alpha-SiC nanoparticles and chemically cross-linked the
polymeric matrix to simultaneously promote the dielectric and mechanical
properties of composites. In this work, a novel strategy of high-temperature
plastification towards a polymeric matrix has been proposed to fabricate ternary
nanocomposites with balanced dielectric and mechanical characteristics by the
solution cast method in order to reduce costs and simplify steps during large
scale preparation. Poly(vinylidene fluoride-chlorotrifluoroethylene) with inner
double bonds as matrix, unfunctionalized alpha-SiC nanoparticles (NPs) as filler,
and dibutyl phthalate (DBP) as plasticizer were employed. By introducing DBP and
high-temperature treatment, the dispersion of NPs and the degree of compactness
of the interface regions were both improved due to the reduced cohesion of the
fluoropolymer, resulting in an increase in the dielectric constant (by 30%) and
breakdown strength (by 57%) as well as the lowering of loss (by 30%) and
conductivity (by 16%) in nanocomposites. Moreover, high-temperature
plastification contributed to the promotion of flexible and tensile properties.
This work might open the door to large-scale fabrication of nanocomposite
dielectrics with high overall properties through the cooperation of the
plasticizer and high temperature.
PMID- 29966240
TI - Impact of the New Cooperative Medical Scheme on the Rural Residents'
Hospitalization Medical Expenses: A Five-Year Survey Study for the Jiangxi
Province in China.
AB - This survey study was conducted to understand the effect of the New Cooperative
Medical Scheme (NCMS) on farmers’ medical expenses through comparing the
information from five investigations and to obtain a scientific basis for a more
applicable NCMS. The survey was carried out through interviewing farmers in their
homes. The multi-phase stratified cluster random sampling was adopted to select 3
counties from all 92 counties of the Jiangxi province, 9 townships from the 3
selected counties, 27 villages from the selected 9 townships, and 60 families
from each village between 2006 and 2014, and a longitudinal comparative analysis
was conducted. The numbers of households/overall sample for the five years were
1924/8082, 1879/8015, 1885/7506, 1890/7857, and 1896/7811, respectively. We
collected family members’ social demographic characteristics, health
resources, and peoples’ health and medical expenses and reimbursement of
each family member. The adjusted hospitalization expenses per capita of township
hospitals and county hospitals were totally on a rising trend. However, the costs
of tertiary hospitals were on a decreasing tendency. In addition, the expenses
for county hospitalization per admission were on an upward trend in general.
Furthermore, the total hospitalization expenses and reimbursement per capita (the
insurance paid out for the hospitalization expenses) were also all on an upward
trend. The proportion of reimbursement also had a tendency of increasing from
24.41% in 2006 to 41.34% in 2014. The costs paid from farmers’ pockets were
fluctuated, but in general all lower than the costs in 2006. Furthermore, the
percentage of hospitalization expenses from farmers’ annual incomes
gradually decreased each year from 56.38% in 2006 to 26.58% in 2014. NCMS program
has had an obvious impact on the hospitalization expenses in the Jiangxi rural
area. It reduced the hospitalization expenses of the tertiary hospitals
significantly. In addition, the program has also encouraged farmers to get more
health care. However, there are still some shortages associated with present
construction of the NCMS. Hence, there is a need for local government to continue
to take effective countermeasures to control the rising trend of hospitalization
expense.
PMID- 29966241
TI - How Organisms Gained Causal Independence and How It Might Be Quantified.
AB - : Two broad features are jointly necessary for autonomous agency: organisational
closure and the embodiment of an objective-function providing a
‘goal’: so far only organisms demonstrate both. Organisational
closure has been studied (mostly in abstract), especially as cell autopoiesis and
the cybernetic principles of autonomy, but the role of an internalised
‘goal’ and how it is instantiated by cell signalling and the
functioning of nervous systems has received less attention. Here I add some
biological ‘flesh’ to the cybernetic theory and trace the
evolutionary development of step-changes in autonomy: (1) homeostasis of
organisationally closed systems; (2) perception-action systems; (3) action
selection systems; (4) cognitive systems; (5) memory supporting a self-model able
to anticipate and evaluate actions and consequences. Each stage is characterised
by the number of nested goal-directed control-loops embodied by the organism,
summarised as will-nestedness N. Organism tegument, receptor/transducer system,
mechanisms of cellular and whole-organism re-programming and organisational
integration, all contribute to causal independence. CONCLUSION: organisms are
cybernetic phenomena whose identity is created by the information structure of
the highest level of causal closure (maximum N), which has increased through
evolution, leading to increased causal independence, which might be quantifiable
by ‘Integrated Information Theory’ measures.
PMID- 29966242
TI - A Pharmacometabolomic Approach to Predict Response to Metformin in Early-Phase
Type 2 Diabetes Mellitus Patients.
AB - Metformin is a first-line medication for type 2 diabetes mellitus (T2DM). Based
on its universal use, the consideration of inter-individual variability and
development of predictive biomarkers are clinically significant. We aimed to
identify endogenous markers of metformin responses using a pharmacometabolomic
approach. Twenty-nine patients with early-phase T2DM were enrolled and orally
administered metformin daily for 6 months. A total of 22 subjects were included
in the final analysis. Patients were defined as responders or non-responders
based on changes in their glycated haemoglobin A1c (HbA1c) from baseline, over 3
months. Urine metabolites at baseline, as well as at the 3 and 6 month follow-ups
after the start of treatment were analysed using gas chromatography-mass
spectrometry and evaluated with multivariate analyses. Metabolites
distinguishable between the two response groups were obtained at baseline, as
well as at the 3 and 6 month follow-ups, and significantly different metabolites
were listed as markers of metformin response. Among the identified metabolites,
citric acid, myoinositol, and hippuric acid levels showed particularly
significant differences between the non-responder and responder groups. We thus
identified different metabolite profiles in the two groups of T2DM patients after
metformin administration, using pharmacometabolomics. These results might
facilitate a better understanding and prediction of metformin response and its
variability in individual patients.
PMID- 29966244
TI - Error Sources and Distinctness of Materials Parameters Obtained by THz-Time
Domain Spectroscopy Using an Example of Oxidized Engine Oil.
AB - Gasoline engine oil (SAE 5W-20) was subjected to thermal oxidization (TO) for
four periods of time (0 h, 48 h, 96 h and 144 h) and exposed to THz-time domain
spectroscopy (TDS) measurement. Error contributions from various error sources,
such as repeatability errors, assembly errors of the probe volume and errors
caused by the TDS system were evaluated with respect to discernibility and
significance of measurement results. The most significant error source was due to
modifications of the TDS setup, causing errors in the range of 0.13% of the
refractive index for samples with a refractive index around 1.467 and a probe
volume length between 5 and 15 mm at 1 THz. The absorption coefficient error was
in the range of 8.49% for an absorption around 0.6 cm−1. While the average
of measurements taken with different setup configurations did not yield
significant differences for different TO times, a single, fixed setup would be
able to discern all investigated oil species across the entire frequency range of
0.5-2.5 THz. The absorption coefficient measurement showed greater discernibility
than the measurement of the refractive index.
PMID- 29966243
TI - Effects of Melatonin on Antioxidant Capacity in Naked Oat Seedlings under Drought
Stress.
AB - Melatonin (N-acetyl-5-methoxytryptamine, MT) is a molecule with pleiotropic
effects including antioxidant activity, regulated plant growth, development, and
reduced environmental stress in plants. However, only a few studies have analyzed
the effect of exogenous MT on drought stress in naked oat seedlings. Therefore,
in this study, we studied the effects of exogenous MT on the antioxidant capacity
of naked oat under drought stress to understand the possible antioxidant
mechanism. The results showed that a pretreatment of 100 μM MT reduced the
hydrogen peroxide (H2O2) and superoxide anion (O2−•) contents. MT also
enhanced superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and
ascorbate peroxidase (APX) activities in the leaves of naked oat seedlings under
20% PEG-6000 drought stress. MT upregulated the expression levels of the mitogen
activated protein kinases (MAPKs) Asmap1 and Aspk11, and the transcription factor
(TF) genes (except for NAC), WRKY1, DREB2, and MYB increased in drought with MT
pretreatment seedlings when compared with seedlings exposed to drought stress
alone. These data indicated that the MT-mediated induction of the antioxidant
response may require the activation of reactive oxygen species (ROS) and MAPK,
followed by triggering a downstream MAPK cascade such as Asmap1 and Aspk11, to
regulate the expression of antioxidant-related genes. This study demonstrated
that MT could induce the expression of MAPKs and TFs and regulate the expression
of downstream stress-responsive genes, thereby increasing the plant’s
tolerance. This may provide a new idea for MT modulation in the regulation of
plant antioxidant defenses. These results provide a theoretical basis for MT to
alleviate drought stress in naked oat.
PMID- 29966247
TI - Kinetic Diffusion Couple for Mapping Microstructural and Mechanical Data on Ti-Al
Mo Titanium Alloys.
AB - We introduce a new strategy that extends the established diffusion couple
approach for efficient mapping of microstructural and mechanical properties in
bulk samples. The featured diffusion couples undergo an interdiffusion annealing
followed by a thermal/mechanical treatment for creating a blended spectrum of
phases and microstructures in the well-grooved continuous composition gradients,
which is then further accessible to local high spatially resolving microanalysis
probing. The strategy is demonstrated on two diffusion couples, Ti/Ti-7.58Al
4.97Mo and Ti-5.04Al/Ti-1.52Mo, by surveying the spectrums of microstructural and
mechanical characteristics created through an appreciation of the β-to
α phase transformation with such microanalysis techniques as electron probe
microanalysis, electron backscatter diffraction analysis, and nanoindentation.
The examined microstructural characteristics and mechanical properties reveal the
variation of phase, morphology, and microhardness based on the changes of the
compositions of the overall alloys and the individual phases in these near-β
Ti alloys.
PMID- 29966246
TI - Diagnosing Lung Cancer: The Complexities of Obtaining a Tissue Diagnosis in the
Era of Minimally Invasive and Personalised Medicine.
AB - The role of the respiratory physician in diagnosing lung cancer has increased in
complexity over the last 20 years. Adenocarcinoma is now the prevailing
histopathological sub-type of non-small cell lung cancer (NSCLC) resulting in
more peripheral cancers. Conventional bronchoscopy is often not sufficient to
obtain adequate tissue samples for diagnosis. Radiologically guided transthoracic
biopsy is a sensitive alternative, but carries significant risks. These
limitations have driven the development of complimentary bronchoscopic navigation
techniques for peripheral tumour localisation and sampling. Furthermore, linear
endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is
increasingly being chosen as the initial diagnostic procedure for those with
central lesions and/or radiological evidence of node-positive disease. This
technique can diagnose and stage patients in a single, minimally invasive
procedure with a diagnostic yield equivalent to that of surgical mediastinoscopy.
The success of molecular targeted therapies and immune checkpoint inhibitors in
NSCLC has led to the increasing challenge of obtaining adequate specimens for
accurate tumour subtyping through minimally invasive procedures. This review
discusses the changing epidemiology and treatment landscape of lung cancer and
explores the utility of current diagnostic options in obtaining a tissue
diagnosis in this new era of precision medicine.
PMID- 29966245
TI - Curcumin-Loaded Solid Lipid Nanoparticles Enhanced Anticancer Efficiency in
Breast Cancer.
AB - Curcumin (Cur) has been widely used in medicine, due to its antibacterial, anti
inflammatory, antioxidant, and antitumor effects. However, its clinic application
is limited by its instability and poor solubility. In the present wok, curcumin
was loaded into solid lipid nanoparticles (SLNs), in order to improve the
therapeutic efficacy for breast cancer. The results measured using transmission
electron microscopy (TEM) indicated that Cur-SLNs have a well-defined spherical
shape; the size was about 40 nm with a negative surface charge. The drug loading
and encapsulation efficiency in SLNs reached 23.38% and 72.47%, respectively. The
Cur-SLNs showed a stronger cytotoxicity against SKBR3 cells. In vitro cellular
uptake study demonstrated a high uptake efficiency of the Cur-SLNs by SKBR3
cells. Moreover, Cur-SLNs induced higher apoptosis in SKBR3 cells, compared to
cells treated by free drug. In addition, Western blot analysis revealed that Cur
SLNs could promote the ratio of Bax/Bcl-2, but decreased the expression of cyclin
D1 and CDK4. These results suggested that Cur-SLNs could be a potential useful
chemotherapeutic formulation for breast cancer therapy.
PMID- 29966248
TI - Surface-Enhanced Raman Scattering Spectroscopy and Microfluidics: Towards
Ultrasensitive Label-Free Sensing.
AB - Raman scattering and surface-enhanced Raman scattering (SERS) spectroscopy have
demonstrated their potential as ultrasensitive detection techniques in the past
decades. Specifically, and as a result of the flourishing of nanotechnology, SERS
is nowadays one of the most powerful sensing techniques, not only because of the
low detection limits that it can achieve, but also for the structural information
that it offers and its capability of multiplexing. Similarly, microfluidics
technology is having an increased presence not only in fundamental research, but
also in the industry. The latter is because of the intrinsic characteristics of
microfluidics, being automation, high-throughput, and miniaturization. However,
despite miniaturization being an advantage, it comes together with the need to
use ultrasensitive techniques for the interrogation of events happening in
extremely small volumes. The combination of SERS with microfluidics can overcome
bottlenecks present in both technologies. As a consequence, the integration of
Raman and SERS in microfluidics is being investigated for the label-free
biosensing of relevant research challenges.
PMID- 29966249
TI - Development and Evaluation of Raloxifene-Hydrochloride-Loaded Supersaturatable
SMEDDS Containing an Acidifier.
AB - Raloxifene hydrochloride (RLH) was formulated into a pH-modified supersaturatable
self-microemulsifying drug delivery system (S-SMEDDS) to increase drug solubility
and dissolution rate. Optimal formulations of pH-modified S-SMEDDSs were
developed by incorporating hydroxypropyl-cellulose-L as a precipitation inhibitor
and phosphoric acid as a pH modifier (an acidifier). RLH was dissolved to greater
extents by all pH-modified S-SMEDDSs compared with non-pH-modified S-SMEDDSs. In
particular, phosphoric acid afforded greater drug dissolution than did the other
acidifiers tested, perhaps because phosphoric acid better controlled the pH. More
than 50% of the RLH was released from the pH-modified S-SMEDDS at pH 2.5 compared
with only ~5% of the drug into aqueous buffer (pH 1.2 or 6.8) after dissolution
of a conventional tablet. pH-modified S-SMEDDSs with a hydrophilic polymer and
phosphoric acid improved the dissolution behavior of a drug exhibiting poor
aqueous solubility.
PMID- 29966250
TI - Biological Roles of Protein-Coding Tandem Repeats in the Yeast Candida Albicans.
AB - Tandem repeat (TR) DNA mutates faster than other DNA by insertion and deletion of
repeats. Large parts of eukaryotic proteomes are encoded by ORFs containing
protein-coding TRs (TR-ORFs, pcTRs) with largely unknown biological consequences.
We explored these in the yeast Candida albicans, an opportunistic human pathogen.
We found that almost half of C. albicans’ proteins are encoded by TR-ORFs.
pcTR frequency differed only moderately between different gene (GO) categories.
Bioinformatic predictions of genome-wide mutation rates and clade-specific
differences in pcTR allele frequencies indicated that pcTRs (i) significantly
increase the genome-wide mutation rate; (ii) significantly impact on fitness and
(iii) allow the evolution of selectively advantageous clade-specific protein
variants. Synonymous mutations reduced the repetitiveness of many amino acid
repeat-encoding pcTRs. A survey, in 58 strains, revealed that in some pcTR
regions in which repetitiveness was not significantly diminished by synonymous
mutations the habitat predicted which alleles were present, suggesting roles of
pcTR mutation in short-term adaptation and pathogenesis. In C. albicans pcTR
mutation apparently is an important mechanism for mutational advance and possibly
also rapid adaptation, with synonymous mutations providing a mechanism for
adjusting mutation rates of individual pcTRs. Analyses of Arabidopsis and human
pcTRs showed that the latter also occurs in other eukaryotes.
PMID- 29966251
TI - Response Time to a Vibrotactile Stimulus Presented on the Foot at Rest and During
Walking on Different Surfaces.
AB - This study investigates the simple reaction time (SRT) and response time (RT) to
a vibrotactile stimulus presented on two body locations at the lower extremity of
the foot on different types of surface during walking. We determined RTs while
walking on Concrete, Foam, Sand, and gravel surface. Also, for RT, we evaluated
two vibrotactile stimulus (VS) locations on the lower extremity: the ankle (AL)
and under the foot plantar (FP). A total of 21 young adult participants (n = 21),
aged mean 24 +/- 2.9 years, took part in a two-session experiment with two main
conditions (at rest and while walking on four types of surface). The control
session included 2016 repeated measures, with one-way and two-way ANOVA analyses.
The findings have consistently revealed slowness of RT to VS, in particular on
sand and gravel surface. In addition, we found that body location has a
significant effect on RT in certain surfaces. These results showed that RTs
increased with environment changes during the performance of dual tasks.
PMID- 29966253
TI - De Novo Transcriptome Sequencing of the Deep-Sea-Derived Fungus Dichotomomyces
cejpii and Analysis of Gliotoxin Biosynthesis Genes.
AB - Gliotoxin, produced by fungi, is an epipolythiodioxopiperazine (ETP) toxin with
bioactivities such as anti-liver fibrosis, antitumor, antifungus, antivirus,
antioxidation, and immunoregulation. Recently, cytotoxic gliotoxins were isolated
from a deep-sea-derived fungus, Dichotomomyces cejpii. However, the biosynthetic
pathway for gliotoxins in D. cejpii remains unclear. In this study, the
transcriptome of D. cejpii was sequenced using an Illumina Hiseq 2000. A total of
19,125 unigenes for D. cejpii were obtained from 9.73 GB of clean reads. Ten
genes related to gliotoxin biosynthesis were annotated. The expression levels of
gliotoxin-related genes were detected through quantitative real-time polymerase
chain reaction (qRT-PCR). The GliG gene, encoding a glutathione S-transferase (DC
GST); GliI, encoding an aminotransferase (DC-AI); and GliO, encoding an aldehyde
reductase (DC-AR), were cloned and expressed, purified, and characterized. The
results suggested the important roles of DC-GST, DC-AT, and DC-AR in the
biosynthesis of gliotoxins. Our study on the genes related to gliotoxin
biosynthesis establishes a molecular foundation for the wider application of
gliotoxins from D. cejpii in the biomedical industry in the future.
PMID- 29966254
TI - Continuous Flow-Constructed Wetlands for the Treatment of Swine Waste Water.
AB - The microbiological quality of treated waste water is always a concern when waste
water is disposed to the environment. However, when treated appropriately, such
water can serve many purposes to the general population. Therefore, the treatment
and removal of contaminants from swine waste water by continuous flow-constructed
wetlands involves complex biological, physical, and chemical processes that may
produce better quality water with reduced levels of contaminants. Swine waste
contains E. coli populations and other bacterial contaminants originating from
swine houses through constructed wetlands, but little is known about E. coli
population in swine waste water. To assess the impacts of seasonal variations and
the effect of the wetland layout/operations on water quality, E. coli isolates
were compared for genetic diversity using repetitive extragenic palindromic
polymerase chain reaction (REP-PCR). None of the isolates was confirmed as Shiga
toxin producing E. coli O157:H7 (STEC); however, other pathotypes, such as
enterotoxigenic E. coli (ETEC) were identified. Using a 90% similarity index from
REP-PCR, 69 genotypes out of 421 E. coli isolates were found. Our data showed
that the E. coli population was significantly (p = 0.036) higher in November than
in March and August in most of the wetland cells. Furthermore, there was a
significant (p = 0.001) reduction in E. coli populations from wetland influent to
the final effluent. Therefore, the use of continuous flow-constructed wetlands
may be a good treatment approach for reducing contaminants from different waste
water sources.
PMID- 29966252
TI - On the Developmental Timing of Stress: Delineating Sex-Specific Effects of Stress
across Development on Adult Behavior.
AB - Stress, and the chronic overactivation of major stress hormones, is associated
with several neuropsychiatric disorders. However, clinical literature on the
exact role of stress either as a causative, triggering, or modulatory factor to
mental illness remains unclear. We suggest that the impact of stress on the brain
and behavior is heavily dependent on the developmental timing at which the stress
has occurred, and as such, this may contribute to the overall variability
reported on the association of stress and mental illness. Here, animal models
provide a way to comprehensively assess the temporal impact of stress on behavior
in a controlled manner. This review particularly focuses on the long-term impact
of stress on behavior in various rodent stress models at three major
developmental time points: early life, adolescence, and adulthood. We
characterize the various stressor paradigms into physical, social, and
pharmacological, and discuss commonalities and differences observed across these
various stress-inducing methods. In addition, we discuss here how sex can
influence the impact of stress at various developmental time points. We conclude
here that early postnatal life and adolescence represent particular periods of
vulnerability, but that stress exposure during early life can sometimes lead to
resilience, particularly to fear-potentiated memories. In the adult brain, while
shorter periods of stress tended to enhance spatial memory, longer periods caused
impairments. Overall, males tended to be more vulnerable to the long-term effects
of early life and adolescent stress, albeit very few studies incorporate both
sexes, and further well-powered sex comparisons are needed.
PMID- 29966255
TI - The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells
via Modulation of Transcription Factors p53/Sp1.
AB - Curcumin is a potential anticancer drug with poor bioavailability, which limits
its clinical use as a therapeutic agent. The aim of this study was a preliminary
evaluation of the curcumin analogue CH-5 as a cytotoxic agent in human
osteosarcoma cell lines U2OS, MG-63, and Saos-2. CH-5 inhibited cell viability at
lower concentrations than curcumin, leading to the induction of apoptosis. The
cellular levels of the transcription factors p53 and Sp1 affect the expression of
cellular pathways that lead to apoptosis. CH-5 increased p53 protein levels in
U2OS cells and reduced Sp1 levels, with a consequent effect on the expression of
their target genes DNA methyltransferase 1 (DNMT1) and growth arrest and DNA
damage-inducible 45 alpha gene (Gadd45a). CH-5 repressed DNMT1 and increased
Gadd45a mRNA expression, which was dependent on p53, as this effect was only
observed in the colorectal cancer cell line HCT116 with active p53, but not in
the isogenic p53-deficient HCT116 cells. CH-5 also reduced the protein levels of
DNMT1, which led to the upregulation of Gadd45a. These results suggest that CH-5
has potentially higher anticancer activity than curcumin, which is associated
with the expression of apoptosis-associated genes regulated by the transcription
factors Sp1 and p53. Future work on CH-5 will define the therapeutic potential of
this compound in vivo.
PMID- 29966256
TI - Cu(II) Complexes of 4-[(1E)-N-{2-[(Z)-Benzylidene
amino]ethyl}ethanimidoyl]benzene-1,3-diol Schiff Base: Synthesis, Spectroscopic,
In-Vitro Antioxidant, Antifungal and Antibacterial Studies.
AB - The current study reports the synthesis of copper complexes of a tridentate
Schiff base ligand. The compounds of the type [Cu(L)X]?n(H2O) (where L =
tridentate ONN Schiff base ligand, X = Cl−, Br−, SCN−,
NO3−, CH3COO−), were characterized on the basis of elemental
analyses, FT-IR, UV-vis, molar conductance, 1H-NMR, XRD and thermal analyses. The
spectra revealed that the Schiff base ligand acts as a tridentate ligand through
two azomethine nitrogen atoms and a phenolic oxygen atom. The molar conductance
measurements of the complexes in DMF correspond to non-electrolytic nature. TGA
and DTA studies results gave insight into the dehydration, thermal stability, and
thermal decomposition. Square-planar geometry has been assigned to the prepared
complexes as indicated by the electronic spectral measurements. Cu(II) compounds
showed antiradical potential against DPPH and ABTS radicals. The antimicrobial
potential of the Schiff base ligand and its Cu(II) complexes were evaluated by
the rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay against some
selected bacteria strains: Staphylococcus aureus and Enterococcus faecalis (Gram
+ve); Klebsiella pneumoniae and Pseudomonas aeruginosa (Gram −ve), and
fungi (Candida albicans and Cryptococcus neoformans). The compounds showed a
broad spectrum of antibacterial and antifungal activities, with MIC values
ranging from 48.83 to 3125 μg/mL.
PMID- 29966258
TI - Fabrication of Superhydrophobic Mg/Al Layered Double Hydroxide (LDH) Coatings on
Medium Density Fiberboards (MDFs) with Flame Retardancy.
AB - The hydrophilicity and flammability of fiberboards have limited their real-life
applications. In this study, a facile strategy for preparing the multifunctional
coatings with superhydrophobicity and flame retardancy on medium density
fiberboards (MDFs) has been investigated. The superhydrophobic and flame
retardant coating on the MDF surface was obtained by depositing
polydimethylsiloxane (PDMS) and 1H, 1H, 2H, 2H-perfluorodecyltrichlorosilane
(FDTS)-modified Mg/Al layered double hydroxide (LDH) particles step by step. The
as-prepared coating exhibited superhydrophobic properties with a water contact
angle (WCA) of ~155° and good self-cleaning properties. Furthermore, the
limiting oxygen index (LOI) value of the superhydrophobic MDFs increased by 60.4%
as compared to that of the pristine MDFs, showing improved flame retardancy. The
peak heat release rate (PHRR) and total heat release (THR) of MDFs decreased
after coating with PDMS@FDTS-Mg/Al LDH, suggesting that the superhydrophobic
coating decreased the fire growth speed and risk of fire hazard of MDFs. This
coating with multiple functions opens a new avenue for the protection and
functionalization of MDFs.
PMID- 29966257
TI - Molecular Cloning and Characterization of a meta/para-O-Methyltransferase from
Lycoris aurea.
AB - O-methyltransferases (OMTs) have been demonstrated to play key roles in the
biosynthesis of plant secondary metabolites, such as alkaloids, isoprenoids, and
phenolic compounds. Here, we isolated and characterized an OMT gene from Lycoris
aurea (namely LaOMT1), based on our previous transcriptome sequencing data.
Sequence alignment and phylogenetic analysis showed that LaOMT1 belongs to the
class I OMT, and shares high identity to other known plant OMTs. Also, LaOMT1 is
highly identical in its amino acid sequence to NpN4OMT, a norbelladine 4′
OMT from Narcissus sp. aff. pseudonarcissus involved in the biosynthesis of
Amaryllidaceae alkaloids. Biochemical analysis indicated that the recombinant
LaOMT1 displayed both para and metaO-methylation activities with caffeic acid and
3,4-dihydroxybenzaldehyde, and showed a strong preference for the meta position.
Besides, LaOMT1 also catalyzes the O-methylation of norbelladine to form 4′
O-methylnorbelladine, which has been demonstrated to be a universal precursor of
all the primary Amaryllidaceae alkaloid skeletons. The results from quantitative
real-time PCR assay indicated that LaOMT1 was ubiquitously expressed in different
tissues of L. aurea, and its highest expression level was observed in the ovary.
Meanwhile, the largest concentration of lycorine and galanthamine were found in
the ovary, whereas the highest level of narciclasine was observed in the bulb. In
addition, sodium chloride (NaCl), cold, polyethylene glycol (PEG), sodium
nitroprusside (SNP), and methyl jasmonate (MeJA) treatments could significantly
increase LaOMT1 transcripts, while abscisic acid (ABA) treatment dramatically
decreased the expression level of LaOMT1. Subcellular localization showed that
LaOMT1 is mainly localized in cytoplasm and endosome. Our results in this study
indicate that LaOMT1 may play a multifunctional role, and lay the foundation for
Amaryllidaceae alkaloid biosynthesis in L. aurea.
PMID- 29966259
TI - The Effect of a Curved Non-Motorized Treadmill on Running Gait Length, Imbalance
and Stride Angle.
AB - Running on a non-motorized, curved-deck treadmill is thought to improve gait
mechanics. It is not known, though, whether the change in gait carries over to
running on a motorized treadmill on level ground. To determine the effect of
running on a curved non-motorized treadmill (CNT) on gait characteristics,
measured during a subsequent bout of running on a traditional motorized treadmill
(TMT), sixteen healthy college-aged participants, aged (mean +/- SD) 20.4 +/- 1.6
years, volunteered to have their gait analyzed while running on a TMT and CNT.
After familiarization with, and a warm-up on, both treadmills, each subject
completed five 4-min bouts of running, alternating between traditional motorized
and curved non-motorized treadmills: TMT-1, CNT-1, TMT-2, CNT-2, and TMT-3.
Variables of interest included step length (m), stride length (m), imbalance
score (%), and stride angle (°), and were measured using Optogait gait
analysis equipment. We found differences in gait characteristics among TMT-1, TMT
2, and TMT-3, which can be attributed to running on the CNT. The results show
that running on a CNT resulted in significant changes in gait characteristics
(step length, stride length, imbalance score and stride angle). These findings
suggest that running on a CNT can significantly influence running gait.
PMID- 29966260
TI - Undercarboxylated Osteocalcin: Experimental and Human Evidence for a Role in
Glucose Homeostasis and Muscle Regulation of Insulin Sensitivity.
AB - Recent advances have indicated that osteocalcin, and in particular its
undercarboxylated form (ucOC), is not only a nutritional biomarker reflective of
vitamin K status and an indicator of bone health but also an active hormone that
mediates glucose metabolism in experimental studies. This work has been supported
by the putative identification of G protein-coupled receptor, class C, group 6,
member A (GPRC6A) as a cell surface receptor for ucOC. Of note, ucOC has been
associated with diabetes and with cardiovascular risk in epidemiological studies,
consistent with a pathophysiological role for ucOC in vivo. Limitations of
existing knowledge include uncertainty regarding the underlying mechanisms by
which ucOC interacts with GPRC6A to modulate metabolic and cardiovascular
outcomes, technical issues with commonly used assays for ucOC in serum, and a
paucity of clinical trials to prove causation and illuminate the scope for novel
health interventions. A key emerging area of research is the role of ucOC in
relation to expression of GPRC6A in muscle, and whether exercise interventions
may modulate metabolic outcomes favorably in part via ucOC. Further research is
warranted to clarify potential direct and indirect roles for ucOC in human health
and cardiometabolic diseases.
PMID- 29966261
TI - Recent Advances in Toll Like Receptor-Targeting Glycoconjugate Vaccines.
AB - Many malignant cell surface carbohydrates resulting from abnormal glycosylation
patterns of certain diseases can serve as antigens for the development of
vaccines against these diseases. However, carbohydrate antigens are usually
poorly immunogenic by themselves, thus they need to be covalently coupled with
immunologically active carrier molecules to be functional. The most well
established and commonly used carriers are proteins. In recent years, the use of
toll-like receptor (TLR) ligands to formulate glycoconjugate vaccines has gained
significant attention because TLR ligands can serve not only as carrier molecules
but also as built-in adjuvants to form fully synthetic and self-adjuvanting
conjugate vaccines, which have several advantages over carbohydrate-protein
conjugates and formulated mixtures with external adjuvants. This article reviews
recent progresses in the development of conjugate vaccines based on TLR ligands.
Two major classes of TLR ligands, lipopeptides and lipid A derivatives will be
covered with more focus on monophosohoryl lipid A (MPLA) and related analogs,
which are TLR4 ligands demonstrated to be able to provoke T cell-dependent,
adaptive immune responses. Corresponding conjugate vaccines have shown promising
application potentials to multiple diseases including cancer.
PMID- 29966263
TI - Scoring Amino Acid Mutations to Predict Avian-to-Human Transmission of Avian
Influenza Viruses.
AB - Avian influenza virus (AIV) can directly cross species barriers and infect humans
with high fatality. Using machine learning methods, the present paper scores the
amino acid mutations and predicts interspecies transmission. Initially, 183
signature positions in 11 viral proteins were screened by the scores of five
amino acid factors and their random forest rankings. The most important amino
acid factor (Factor 3) and the minimal range of signature positions (50 amino
acid residues) were explored by a supporting vector machine (the highest
performing classifier among four tested classifiers). Based on these results, the
avian-to-human transmission of AIVs was analyzed and a prediction model was
constructed for virology applications. The distributions of human-origin AIVs
suggested that three molecular patterns of interspecies transmission emerge in
nature. The novel findings of this paper provide important clues for future
epidemic surveillance.
PMID- 29966262
TI - Nitric Oxide Is Required for Melatonin-Enhanced Tolerance against Salinity Stress
in Rapeseed (Brassica napus L.) Seedlings.
AB - Although melatonin (N-acetyl-5-methoxytryptamine) could alleviate salinity stress
in plants, the downstream signaling pathway is still not fully characterized.
Here, we report that endogenous melatonin and thereafter nitric oxide (NO)
accumulation was successively increased in NaCl-stressed rapeseed (Brassica napus
L.) seedling roots. Application of melatonin and NO-releasing compound not only
counteracted NaCl-induced seedling growth inhibition, but also reestablished
redox and ion homeostasis, the latter of which are confirmed by the alleviation
of reactive oxygen species overproduction, the decreases in thiobarbituric acid
reactive substances production, and Na+/K+ ratio. Consistently, the related
antioxidant defense genes, sodium hydrogen exchanger (NHX1), and salt overly
sensitive 2 (SOS2) transcripts are modulated. The involvement S-nitrosylation, a
redox-based posttranslational modification triggered by NO, is suggested. Further
results show that in response to NaCl stress, the increased NO levels are
strengthened by the addition of melatonin in seedling roots. Above responses are
abolished by the removal of NO by NO scavenger. We further discover that the
removal of NO does not alter endogenous melatonin content in roots supplemented
with NaCl alone or together with melatonin, thus excluding the possibility of NO
triggered melatonin production. Genetic evidence reveals that, compared with wild
type Arabidopsis, the hypersensitivity to NaCl in nia1/2 and noa1 mutants
(exhibiting null nitrate reductase activity and indirectly reduced endogenous NO
level, respectively) cannot be rescued by melatonin supplementation. The
reestablishment of redox homeostasis and induction of SOS signaling are not
observed. In summary, above pharmacological, molecular, and genetic data conclude
that NO operates downstream of melatonin promoting salinity tolerance.
PMID- 29966264
TI - Triorganoindium Reagents in Rh-Catalyzed C-H Activation/C-C Cross-Coupling
Reactions of 2-Arylpyridines.
AB - The activation of C-H bonds through catalytic reactions using transition metals
is an important challenge in organic chemistry in which the intermediates are
related to those produced in the classical cross-coupling reactions. As part of
our research program devoted to the development of metal-catalyzed reactions
using indium organometallics, a protocol for the C-H activation and C-C coupling
of 2-arylpyridines with triorganoindium reagents under Rh(I) catalysis is
reported. Under the optimized conditions, we found that Me3In and Ar3In reagents
reacted with 2-arylpyridines and related compounds in the presence of
Rh(PPh3)3Cl, in PhCl/THF (9:1), at 120 °C for 48 h, to afford the ortho
coupling products in moderate to good yields. The nitrogen atom in the pyridine
ring acts as a directing group to assist the functionalization at the ortho
position of the aryl group forming a new C-C bond at this position.
PMID- 29966265
TI - Selenium Improves Physiological Parameters and Alleviates Oxidative Stress in
Strawberry Seedlings under Low-Temperature Stress.
AB - Here, we investigated the effects of selenium (Se) applications on two strawberry
varieties, Akihime and Benihoppe, under chilling stress and recovery conditions.
Changes in photosynthetic parameters, antioxidant enzyme activities, ascorbate
(AsA)-glutathione (GSH) cycle-related enzyme activities, and low-molecular-mass
antioxidant contents were determined. Foliar spraying with Se alleviated the
decline in the net photosynthetic rate and chlorophyll content and increased the
malondialdehyde and hydrogen peroxide contents of strawberry seedlings’
leaves under chilling stress. As the time under chilling stress increased, the
stomatal conductance decreased and intercellular CO2 concentration increased,
suggesting that nonstomatal factors had major limiting effects on the net
photosynthetic rate’s decrease. Se applications significantly alleviated
the adverse impacts of chilling stress on changes in stomatal conductance and
intercellular CO2 concentration. Se, especially at lower concentrations,
significantly increased superoxide dismutase, catalase, and peroxide enzyme
activities during chilling stress. Approximately 5 mg·L−1 of sodium
selenite solution had the greatest stress-alleviating effects. Among the AsA-GSH
cycle-related enzymes, ascorbate peroxidase, glutathione reductase,
dehydroascorbate reductase, and monodehydroascorbate reductase (MDHAR)
treatments, coupled with an appropriate dose of Se, significantly enhanced
ascorbate peroxidase and MDHAR activities, which suggested that Se applications
played important roles in strawberry leaves by affecting AsA-GSH cycle-related
defenses against the oxidative damage caused by chilling stress. Furthermore,
MDHAR was the key enzyme required to maintain the balance between AsA consumption
and regeneration that may assist in protecting strawberry seedlings in a low
temperature environment.
PMID- 29966266
TI - Lipase Catalysed Kinetic Resolution of Racemic 1,2-Diols Containing a Chiral
Quaternary Center.
AB - Optically active 1,2-diols are valuable buildings blocks in organic synthesis. In
the present paper, a set of racemic 1,2-diols with an ester functional group are
prepared, starting from α-ketoesters in a three-step procedure with
moderate yields. The racemic 1,2-diols, containing a chiral quaternary center in
their structure, are subjected to selective acylation in order to perform their
kinetic resolution catalysed by a set of commercially available lipases. Under
optimized reaction conditions, good conversions and enantioselectivities are
achieved by using the lipase PSL-C from Pseudomonas cepacia in tert-butyl methyl
ether. This biocatalyst could be reused up to five times without losing its
properties.
PMID- 29966267
TI - A Novel Approach for Mapping Wheat Areas Using High Resolution Sentinel-2 Images.
AB - Global wheat production reached 754.8 million tons in 2017, according to the FAO
database. While wheat is considered as a staple food for many populations across
the globe, mapping wheat could be an effective tool to achieve the SDG2
sustainable development goal—End Hunger and Secure Food Security. In
Lebanon, this crop is supported financially, and sometimes technically, by the
Lebanese government. However, there is a lack of statistical databases, at both
national and regional scales, as well as critical information much needed in the
subsidy and compensation system. In this context, this study proposes an
innovative approach, named Simple and Effective Wheat Mapping Approach (SEWMA),
to map the winter wheat areas grown in the Bekaa plain, the primary wheat
production area in Lebanon, in the years of 2016 and 2017. The proposed
methodology is a tree-like approach relying on the Normalized Difference
Vegetation Index (NDVI) values of four-month period that coincides with several
phenological stages of wheat (i.e., tillering, stem extension, heading, flowering
and ripening). The usage of the freely available Sentinel-2 imageries, with a
high spatial (10 m) and temporal (5 days) resolutions, was necessary,
particularly due to the small sized and overlapped plots encountered in the study
area. Concerning the wheat areas, results show that there was a decrease from
11,063 +/- 1309 ha in 2016 to 7605 +/- 1184 in 2017. When SEWMA was applied using
2016 ground truth data, the overall accuracy reached 87.0% on 2017 data, whereas,
when implemented using 2017 ground truth data, the overall accuracy was 82.6% on
2016 data. The novelty resides in executing early classification output (up to
six weeks before harvest) as well as distinguishing wheat from other winter
cereal crops with similar NDVI yearly profiles (i.e., barley and triticale).
SEWMA offers a simple, yet effective and budget-saving approach providing early
season classification information, very crucial to decision support systems and
the Lebanese government concerning, but not limited to, food production, trade,
management and agricultural financial support.
PMID- 29966268
TI - Listeria monocytogenes Response to Propionate Is Differentially Modulated by
Anaerobicity.
AB - Propionate is a common food preservative and one of the major fermentation acids
in the intestines. Therefore, exposure to propionate is frequent for foodborne
pathogens and likely takes place under suboxic conditions. However, it is not
clear whether the absence of oxygen affects how pathogens respond to propionate.
Here, we investigated how propionate exposure affects Listeria monocytogenes
growth and virulence factor production under aerobic or anaerobic conditions and
showed that oxygen indeed plays a key role in modulating L. monocytogenes
response to propionate. Under aerobic conditions, propionate supplementations had
no effect on planktonic growth but resulted in decreased adherent growth. Under
anaerobic conditions, propionate supplementations resulted in a pH-dependent
inhibition of planktonic growth and increased adherent growth. Cultures grown
with propionate accumulated higher levels of acetoin under aerobic conditions but
lower levels of ethanol under both aerobic and anaerobic conditions. Metabolic
perturbations by propionate were also evident by the increase in straight chain
fatty acids. Finally, propionate supplementations resulted in increased
listeriolyin O (LLO) production under anaerobic conditions but decreased LLO
production under aerobic conditions. These results demonstrate for the first time
that the presence or absence of oxygen plays a critical role in shaping L.
monocytogenes responses to propionate.
PMID- 29966269
TI - Fabrication of Sputtered Ce/La, La/Ce Oxide Bilayers on AA6061 and AA7075
Aluminum Alloys for the Development of Corrosion Protective Coatings.
AB - This work provides a comparative study on the corrosion protection efficiency of
Ce, La films as well as Ce/La and La/Ce oxide bilayered coatings deposited onto
AA7075 and AA6061 substrates by the radio frequency (RF) magnetron sputtering
technique. The coating thickness ranged approximately from 12 to 835 nm, which
changed with the deposition parameters and substrate composition. The
relationship between microstructure, roughness and electrochemical performance is
examined. The reactivity and crystallinity of rare earth (RE) films can be
tailored by adjusting the sputtering parameters. Sputtered La films with
thickness ca. 390 nm and average roughness of 66 nm showed the best corrosion
protection properties in chloride medium as determined by potentiodynamic curves
and electrochemical impedance spectroscopy (EIS). The method to obtain RE
bilayered coatings, i.e., La/Ce or Ce/La as well as the substrate composition and
applied power conditioned their inhibition properties. The RE bilayered coatings
displayed better barrier properties than Ce films, which were poorer than those
featured by La films.
PMID- 29966270
TI - Gut Microbiome and Cardiovascular Diseases.
AB - Recent evidence has suggested that the gut microbiome is involved in human health
and diseases, such as inflammatory bowel disease, liver cirrhosis, rheumatoid
arthritis, and type 2 diabetes. Cardiovascular diseases, which are associated
with high morbidity and mortality across the world, are no exception. Increasing
evidence has suggested a strong relationship between the gut microbiome and the
progression of cardiovascular diseases. We first reported such a relationship
with coronary artery disease two years ago. Next-generation sequencing
techniques, together with bioinformatics technology, constantly and dramatically
expand our knowledge of the complex human gut bacterial ecosystem and reveal the
exact role of this bacterial ecosystem in cardiovascular diseases via the
functional analysis of the gut microbiome. Such knowledge may pave the way for
the development of further diagnostics and therapeutics for prevention and
management of cardiovascular diseases. The aim of the current review is to
highlight the relationship between the gut microbiome and their metabolites, and
the development of cardiovascular diseases by fostering an understanding of
recent studies.
PMID- 29966271
TI - Bovine Lactoferrin Modulates Dendritic Cell Differentiation and Function.
AB - Lactoferrin is an abundant glycoprotein in bovine milk that has immunomodulatory
effects on human cells. Bovine lactoferrin (LF) binds lipopolysaccharides (LPS)
with high affinity and is postulated to act via TLR4-dependent and -independent
mechanisms. It has been shown that LF modulates differentiation of human
monocytes into tolerogenic dendritic cells. However, in a previous study, we
showed that LPS also mediates differentiation into tolerogenic dendritic cells
(DC). Since LF binds LPS with high affinity, it remains to be investigated
whether LF or LPS is mediating these effects. We, therefore, further investigated
the LPS-independent effect of LF on differentiation of human monocytes into
dendritic cells (DC). Human monocytes were isolated by magnetic cell sorting from
freshly isolated PBMCs and cultured for six days in the presence of IL-4 and GM
CSF with or without LF or proteinase K treated LF to generate DC. These immature
DC were stimulated for 48 h with LPS or Poly I:C + R848. Cell surface marker
expression and cytokine production were measured by flow cytometry. DC
differentiated in the presence of LF produced higher IL-6 and IL-8 levels during
differentiation and showed a lower expression of CD1a and HLA-DR. These LFDCs
showed to be hyporesponsive towards TLR ligands as shown by their semi-mature
phenotype and reduced cytokine production. The effect of LF was abrogated by
proteinase K treatment, showing that the functional effects of LF were not
mediated by LPS contamination. Thus, LF alters DC differentiation and dampens
responsiveness towards TLR ligands. This study indicates that LF can play a role
in immune homeostasis in the human GI tract.
PMID- 29966272
TI - Theoretical Characterization by Density Functional Theory (DFT) of Delphinidin 3
O-Sambubioside and Its Esters Obtained by Chemical Lipophilization.
AB - Anthocyanins are water-soluble phenolic pigments. However, their poor solubility
in lipidic media limits their use. This hurdle can be overcome with the
lipophilization of anthocyanins, which consists of adding an aliphatic chain to a
hydrophilic compound, in order to increase its solubility in lipids. Still, the
unspecific chemical lipophilization of anthocyanin-esters produces molecules with
different properties from their precursors. In this work, experimental changes of
anthocyanin-esters obtained by chemical lipophilization are investigated in
silico aiming specifically at observing their molecular behavior and comparing it
with their anthocyanin precursor. Thus, the analysis of delphinidin 3-O
sambubioside and its esters employing Density Functional Theory (DFT) methods,
such as the hybrid functional B3LYP in combination with the 6-31++G(d,p) Pople
basis set, provides the ground state properties, the local reactivity and the
molecular orbitals (MOs) of these compounds. Excited states properties were
analyzed by TD-DFT with the B3LYP functional, and the M06 and M06-2X meta-GGA
functionals. Local reactivity calculations showed that the electrophilic site for
all the anthocyanin-esters was the same as the one for the anthocyanin precursor,
however the nucleophilic site changed depending localization of the
esterification. TD-DFT results indicate that the place of esterification could
change the electronic transitions and the MOs spatial distribution.
PMID- 29966273
TI - The Mechanism for siRNA Transmembrane Assisted by PMAL.
AB - The capacity of silencing genes makes small interfering RNA (siRNA) appealing for
curing fatal diseases. However, the naked siRNA is vulnerable to and degraded by
endogenous enzymes and is too large and too negatively charged to cross cellular
membranes. An effective siRNA carrier, PMAL (poly(maleic anhydride-alt-1-decene)
substituted with 3-(dimethylamino) propylamine), has been demonstrated to be able
to assist siRNA transmembrane by both experiments and molecular simulation. In
the present work, the mechanism of siRNA transmembrane assisted by PMAL was
studied using steered molecular dynamics simulations based on the martini coarse
grained model. Here two pulling rates, i.e., 10−6 and 10−5
nm·ps−1, were chosen to imitate the passive and active transport of
siRNA, respectively. Potential of mean force (PMF) and interactions among siRNA,
PMAL, and lipid bilayer membrane were calculated to describe the energy change
during siRNA transmembrane processes at various conditions. It is shown that PMAL
assisted siRNA delivery is in the mode of passive transport. The PMAL can help
siRNA insert into lipid bilayer membrane by lowering the energy barrier caused by
siRNA and lipid bilayer membrane. PMAL prefers to remain in the lipid bilayer
membrane and release siRNA. The above simulations establish a molecular insight
of the interaction between siRNA and PMAL and are helpful for the design and
applications of new carriers for siRNA delivery.
PMID- 29966274
TI - Utilization of Quercetin as an Oviposition Stimulant by Lab-Cultured
Coleomegillamaculata in the Presence of Conspecifics and a Tissue Substrate.
AB - BACKGROUND: The discovery of natural products to improve the reproductive
performance of mass-reared predators is an important aim for successful
augmentative biological control. We tested the hypothesis that quercetin (a
bioflavonoid) stimulates oviposition by the ladybird beetle Coleomegillamaculata
in the presence of conspecifics and a tissue substrate. METHODS: We conducted
bioassays in solitary cages (housing one female) and communal cages (housing 10
females) to estimate daily oviposition site preferences, egg production in
response to quercetin in the presence or absence of a tissue paper substrate, and
female “resting” positions. RESULTS: Females preferentially
oviposited within 1-2 cm of quercetin powder, held in a tiny dish, at the base of
cages. When given a choice, females oviposited in the dish with quercetin over a
tissue paper substrate. In one of two experiments, they produced more egg
clutches, regardless of oviposition site, when the quercetin and tissue were in
close juxtaposition. Females “rested” on the tissue in the presence
or absence of quercetin. CONCLUSION: This study provides evidence that quercetin
can be utilized as an oviposition stimulant by C. maculata in a rearing system.
Future research should determine if quercetin stimulates oviposition in other
ladybird beetle species.
PMID- 29966275
TI - Chemical Structures and Biological Activities of Limonoids from the Genus
Swietenia (Meliaceae).
AB - Swietenia is a genus in the plant family Meliaceae. This genus contains seven to
eight known species, found in the tropical and subtropical regions of the
Americas and West Africa. Thus far, more than 160 limonoids have been isolated
from four species of the genus Swietenia. Limonoids are rich in structure type
and biological activity, and these compounds are the main active components in
the Swietenia species. This paper will give a comprehensive overview of the
recent phytochemical and pharmacological research on the terpenes from Swietenia
plants and encourage further drug discovery research.
PMID- 29966276
TI - Automated Method for Discrimination of Arrhythmias Using Time, Frequency, and
Nonlinear Features of Electrocardiogram Signals.
AB - We developed an automated approach to differentiate between different types of
arrhythmic episodes in electrocardiogram (ECG) signals, because, in real-life
scenarios, a software application does not know in advance the type of arrhythmia
a patient experiences. Our approach has four main stages: (1) Classification of
ventricular fibrillation (VF) versus non-VF segments—including atrial
fibrillation (AF), ventricular tachycardia (VT), normal sinus rhythm (NSR), and
sinus arrhythmias, such as bigeminy, trigeminy, quadrigeminy, couplet,
triplet—using four image-based phase plot features, one frequency domain
feature, and the Shannon entropy index. (2) Classification of AF versus non-AF
segments. (3) Premature ventricular contraction (PVC) detection on every non-AF
segment, using a time domain feature, a frequency domain feature, and two
features that characterize the nonlinearity of the data. (4) Determination of the
PVC patterns, if present, to categorize distinct types of sinus arrhythmias and
NSR. We used the Massachusetts Institute of Technology-Beth Israel Hospital (MIT
BIH) arrhythmia database, Creighton University’s VT arrhythmia database,
the MIT-BIH atrial fibrillation database, and the MIT-BIH malignant ventricular
arrhythmia database to test our algorithm. Binary decision tree (BDT) and support
vector machine (SVM) classifiers were used in both stage 1 and stage 3. We also
compared our proposed algorithm’s performance to other published
algorithms. Our VF detection algorithm was accurate, as in balanced datasets (and
unbalanced, in parentheses) it provided an accuracy of 95.1% (97.1%), sensitivity
of 94.5% (91.1%), and specificity of 94.2% (98.2%). The AF detection was
accurate, as the sensitivity and specificity in balanced datasets (and
unbalanced, in parentheses) were found to be 97.8% (98.6%) and 97.21% (97.1%),
respectively. Our PVC detection algorithm was also robust, as the accuracy,
sensitivity, and specificity were found to be 99% (98.1%), 98.0% (96.2%), and
98.4% (99.4%), respectively, for balanced and (unbalanced) datasets.
PMID- 29966277
TI - Implementation of Industrial Additive Manufacturing: Intelligent Implants and
Drug Delivery Systems.
AB - The purpose of this study is to demonstrate the ability of additive
manufacturing, also known as 3D printing, to produce effective drug delivery
devices and implants that are both identifiable, as well as traceable. Drug
delivery devices can potentially be used for drug release in the direct vicinity
of target tissues or the selected medication route in a patient-specific manner
as required. The identification and traceability of additively manufactured
implants can be administered through radiofrequency identification systems. The
focus of this study is to explore how embedded medication and sensors can be
added in different additive manufacturing processes. The concept is extended to
biomaterials with the help of the literature. As a result of this study, a
patient-specific drug delivery device can be custom-designed and additively
manufactured in the form of an implant that can identify, trace, and dispense a
drug to the vicinity of a selected target tissue as a patient-specific function
of time for bodily treatment and restoration.
PMID- 29966278
TI - Education and Income Predict Future Emotional Well-Being of Whites but Not
Blacks: A Ten-Year Cohort.
AB - BACKGROUND: The Minorities’ Diminished Return (MDR) theory is defined as
systematically smaller effects of socioeconomic status (SES) on the health and
well-being of minority groups when compared to Whites. To extend the existing
literature on the MDR theory as applied to the change of mental well-being over
time, we investigated Black-White differences in the effects of baseline
education and income on subsequent changes in positive and negative affect over a
ten-year period. METHODS: The Midlife in the United States (MIDUS) is a 10-year
longitudinal study of American adults. This analysis followed 3731 adults who
were either Whites (n = 3596) or Blacks (n = 135) for 10 years. Education and
income, as measured at baseline and 10 years later, were the independent
variables. Negative and positive affect, measured at baseline and over ten years
of follow up, were the dependent variables. Covariates were age, gender, and
physical health (body mass index, self-rated health, and chronic medical
conditions), measured at baseline. Race was the focal moderator. We ran multi
group structural equation modeling in the overall sample, with race defining the
groups. RESULTS: High education at baseline was associated with an increase in
income over the 10-year follow up period for Whites but not Blacks. An increase
in income during the follow up period was associated with an increase in the
positive affect over time for Whites but not Blacks. CONCLUSION: The MDR theory
is also relevant to the effects of baseline education attainment on subsequent
changes in income and then in turn on positive affect over time. The relative
disadvantage of Blacks in comparison to Whites in receiving mental health gains
from SES may reflect structural racism and discrimination in the United States.
There is a need for additional research on specific societal barriers that
minimize Blacks’ mental health gains from their SES resources, such as
education and income. There is also a need for policies and programs that help
Blacks to leverage their SES resources.
PMID- 29966279
TI - New Records of Potent In-Vitro Antidiabetic Properties of Dalbergia tonkinensis
Heartwood and the Bioactivity-Guided Isolation of Active Compounds.
AB - Alpha-glucosidase inhibitory activity has been commonly used for the evaluation
of antidiabetic property in vitro. The aim of this study is to investigate and
characterize Dalbergia tonkinensis as a potential source of antidiabetic
compounds. The screening of the active parts used, such as trunk bark, heartwood,
and the leaves of Dalbergia tonkinensis indicated that all these extracted parts
used with methanol demonstrated potent α-glucosidase inhibitory activity.
The in vitro antidiabetic property of Dalbergia tonkinensis was notably recorded
for the first time and showed activity (EC50 = 0.17-0.78 mg/mL) comparable to
those of reported potent herbal extracts (EC50 = 0.25-4.0 mg/mL) and higher
activity than that of acarbose, a commercial antidiabetic drug (EC50 = 1.21
mg/mL). The stability tests revealed that the heartwood of Dalbergia tonkinensis
extract (HDT) possesses high pH stability with relative activity in the range of
80-98%. Further bioassay-guided purification led to the isolation of 2 active
compounds identified as sativanone and formononetin from the ethyl acetate
fraction and water fraction of HDT, respectively. These α-glucosidase
inhibitors (aGIs) show promising inhibition against various types of α
glucosidases. Remarkably, these inhibitors were determined as new mammalian aGIs,
showing good effect on rat α-glucosidase. The results suggest that
Dalbergia tonkinensis is a potent source of aGIs and suggest promise in being
developed as functional food with antidiabetic efficacy. The results of this
study also enrich our knowledge concerning current biological activity and
constituents of Dalbergia tonkinensis species.
PMID- 29966280
TI - Sales and Advertising Channels of New Psychoactive Substances (NPS): Internet,
Social Networks, and Smartphone Apps.
AB - In the last decade, the trend of drug consumption has completely changed, and
several new psychoactive substances (NPS) have appeared on the drug market as
legal alternatives to common drugs of abuse. Designed to reproduce the effects of
illegal substances like cannabis, ecstasy, cocaine, or ketamine, NPS are only in
part controlled by UN conventions and represent an emerging threat to global
public health. The effects of NPS greatly differ from drug to drug and relatively
scarce information is available at present about their pharmacology and potential
toxic effects. Yet, compared to more traditional drugs, more dangerous short- and
long-term effects have been associated with their use, and hospitalizations and
fatal intoxications have also been reported after NPS use. In the era of
cyberculture, the Internet acts as an ideal platform to promote and market these
compounds, leading to a global phenomenon. Hidden by several aliases, these
substances are sold across the web, and information about consumption is shared
by online communities through drug fora, YouTube channels, social networks, and
smartphone applications (apps). This review intends to provide an overview and
analysis of social media that contribute to the popularity of NPS especially
among young people. The possibility of using the same channels responsible for
their growing diffusion to make users aware of the risks associated with NPS use
is proposed.
PMID- 29966281
TI - Elucidation of the Relationship between CD Cotton Effects and the Absolute
Configuration of Sixteen Stereoisomers of Spiroheterocyclic-Lactams.
AB - As part of research to search for antitumor agents in fungi originating from
marine organisms, cephalimysins E-L were isolated from a culture broth of
Aspergillus fumigatus that was separated from the marine fish Mugil cephalus. One
and two-dimensional nuclear magnetic resonance spectra revealed their planar
structures, which are diastereomers of each other. Their absolute
stereostructures were established by epimerization at C-8 with acidic methanol,
nuclear Overhauser effect spectroscopy (NOESY), and circular dichroism (CD)
spectroscopy. These demonstrated the detailed relationships between absolute
configuration and CD Cotton effects. Additionally, in the growth inhibition assay
against P388, HL-60, L1210, and KB cell lines, some of the fungal metabolites or
reaction products exhibited moderate activities.
PMID- 29966282
TI - Boron-Doping Proximity Effects on Dislocation Generation during Non-Planar MPCVD
Homoepitaxial Diamond Growth.
AB - Epitaxial lateral growth will be required if complex diamond-based device
architecture, such as, for example, Metal-oxide-semiconductor Field-effect
transistors (MOSFETs) or epitaxial lateral overgrowth (ELO) substrates, need to
be developed for high-power applications. To this end, undoped and doped non
planar homoepitaxial diamond were overgrown on (001)-oriented diamond-patterned
substrates. Defects induced by both the heavy boron doping and three-dimensional
(3D) growth were studied by transmission electron microscopy (TEM). At high
methane and boron concentrations, threading dislocations with Burgers vectors b =
1/6 ⟨211⟩, b = 1/2 ⟨110⟩, or both were observed. Their
generation mechanisms were established, revealing boron proximity effects as
precursors of dislocations generated in boron-doped samples and providing clues
as to the different Burgers vectors. The concentration ranges of boron and
methane resulting in good crystalline quality depended on the plane of growth.
The microwave plasma-enhanced chemical vapour deposition (MPCVD) growth
conditions and the maximum boron concentration versus plane orientation yielding
a dislocation-free diamond epitaxial layer were determined.
PMID- 29966283
TI - Utilization of Multisensor Data Fusion for Magnetic Nondestructive Evaluation of
Defects in Steel Elements under Various Operation Strategies.
AB - Increasing the number of inspection sources creates an opportunity to combine
information in order to properly set the operation of the entire system, not only
in terms of such factors as reliability, confidence, or accuracy, but inspection
time as well. In this paper, a magnetic sensor-array-based nondestructive system
was applied to inspect defects inside circular-shaped steel elements. The
experiments were carried out for various sensor network strategies, followed by
the fusion of multisensor data for each case. In order to combine the
measurements, first data registration and then four algorithms based on spatial
and transformed representations of sensor signals were applied. In the case of
spatial representation, the data were combined using an algorithm operating
directly on input signals, allowing pooling of information. To build the
transformed representation, a multiresolution analysis based on the Laplacian
pyramid was used. Finally, the quality of the obtained results was assessed. The
details of algorithms are given and the results are presented and discussed. It
is shown that the application of data fusion rules for magnetic multisensor
inspection systems can result in the growth of reliability of proper
identification and classification of defects in steel elements depending on the
utilized configuration of the sensor network.
PMID- 29966284
TI - Smart Sensing of Pavement Temperature Based on Low-Cost Sensors and V2I
Communications.
AB - Nowadays, the preservation, maintenance, rehabilitation, and improvement of road
networks are key issues. Pavement condition is highly affected by environmental
factors such as temperature and humidity, hence the importance of building
databases enriched with real-time information from monitoring systems that enable
the analysis and modeling of the road properties. Information and communication
technologies, and specifically wireless sensor networks and computational
intelligence methods, are enabling the design of new monitoring systems. The main
goal of this work is the design of a pavement monitoring system for measuring
temperature at internal layers. The proposed solution is based on low-cost and
robust temperature sensors, vehicle-to-infrastructure communications, allowing
one to transmit information directly from probes to a moving auscultation
vehicle, and a neural network-based model for prediction pavement temperature.
User requirements drive probes’ design to a modular device, with easy
installation, low cost, and reduced energy consumption. Results of the test and
validation experiments show both the benefits and viability of the proposed
system, which reflect in an accuracy improvement and reduction in routine test
duration. Finally, data collected over a year is applied to assess the
performance of BELLS3 models and the suggested neural network for predicting
pavement temperature. The dynamic behavior of the predicted temperature and the
mean absolute error of the neural network-based model are better than the BELL3
model, demonstrating the suitability of the proposed pavement monitoring system.
PMID- 29966285
TI - Pufferfish Saxitoxin and Tetrodotoxin Binding Protein (PSTBP) Analogues in the
Blood Plasma of the Pufferfish Arothron nigropunctatus, A. hispidus, A.
manilensis, and Chelonodon patoca.
AB - Pufferfish saxitoxin and tetrodotoxin (TTX) binding protein (PSTBP) is a
glycoprotein that we previously isolated from the blood plasma of the pufferfish
Takifugu pardalis; this protein was also detected in seven species of the genus
Takifugu. We proposed that PSTBP is a carrier protein for TTX in pufferfish;
however, PSTBP had not yet been found in genera other than Takifugu. In this
study, we investigated the presence of PSTBP-like proteins in the toxic
pufferfish Arothron nigropunctatus, A. hispidus, A. manilensis, and Chelonodon
patoca. On the basis of ultrafiltration experiments, TTX was found to be present
and partially bound to proteins in the plasma of these pufferfish, and Western
blot analyses with anti-PSTBP antibody revealed one or two bands per species. The
observed decreases in molecular mass following deglycosylation with
glycopeptidase F suggest that these positive proteins are glycoproteins. The
molecular masses of the deglycosylated proteins detected in the three Arothron
species were larger than that of PSTBP in the genus Takifugu, whereas the two
bands detected in C. patoca had molecular masses similar to that of tributyltin
binding protein-2 (TBT-bp2). The N-terminal amino acid sequences of 23-29
residues of these detected proteins were all homologous with those of PSTBP and
TBT-bp2.
PMID- 29966286
TI - Passive Location Resource Scheduling Based on an Improved Genetic Algorithm.
AB - With the development of science and technology, modern communication scenarios
have put forward higher requirements for passive location technology. However,
current location systems still use manual scheduling methods and cannot meet the
current mission-intensive and widely-distributed scenarios, resulting in
inefficient task completion. To address this issue, this paper proposes a method
called multi-objective, multi-constraint and improved genetic algorithm-based
scheduling (MMIGAS), contributing a centralized combinatorial optimization model
with multiple objectives and multiple constraints and conceiving an improved
genetic algorithm. First, we establish a basic mathematical framework based on
the structure of a passive location system. Furthermore, to balance performance
with respect to multiple measures and avoid low efficiency, we propose a multi
objective optimal function including location accuracy, completion rate and
resource utilization. Moreover, to enhance its practicability, we formulate
multiple constraints for frequency, resource capability and task cooperation. For
model solving, we propose an improved genetic algorithm with better convergence
speed and global optimization ability, by introducing constraint-proof
initialization, a penalty function and a modified genetic operator. Simulations
indicate the good astringency, steady time complexity and satisfactory location
accuracy of MMIGAS. Moreover, compared with manual scheduling, MMIGAS can improve
the efficiency while maintaining high location precision.
PMID- 29966287
TI - A Serological Diagnosis of Coeliac Disease Is Associated with Osteoporosis in
Older Australian Adults.
AB - Previously thought to be mainly a disorder of childhood and early adult life,
coeliac disease (CeD) is increasingly diagnosed in older adults. This may be
important given the association between CeD and osteoporosis. The primary aim of
this study was to determine the seroprevalence of undiagnosed CeD (‘at-risk
serology’) in an older Australian community and relate this to a diagnosis
of osteoporosis and fractures during a follow-up period of 12 years. We included
participants from the Hunter Community Study (2004-2007) aged 55-85, who had anti
tissue transglutaminase (tTG) titres, human leukocyte antigen (HLA) genotypes,
and bone mineral density measurements at baseline. Follow-up data included
subsequent diagnosis of CeD and fractures using hospital information. ‘At
risk’ serology was defined as both tTG and HLA positivity. Complete results
were obtained from 2122 patients. The prevalence of ‘at-risk’
serology was 5%. At baseline, 3.4% fulfilled criteria for a diagnosis of
osteoporosis. During a mean of 9.7 years of follow-up, 7.4% of the cohort
suffered at least one fracture and 0.7% were subsequently diagnosed with CeD. At
risk serology was significantly associated with osteoporosis in a multivariate
model (odds ratio 2.83, 95% confidence interval 1.29-6.22); there was
insufficient power to look at the outcome of fractures. The results of this study
demonstrate that at-risk CeD serology was significantly associated with
concurrent osteoporosis but not future fractures. Most individuals with a
serological diagnosis of CeD were not diagnosed with CeD during the follow-up
period according to medical records. Coeliac disease likely remains under
diagnosed.
PMID- 29966289
TI - Fat Mass Is Associated with Serum 25-Hydroxyvitamin D Concentration Regardless of
Body Size in Men.
AB - There are no large community-based studies examining the association of body size
vs. body fat with vitamin D status. Association of serum 25-hydroxyvitamin D
(25OHD) with body weight and subcategories of body weight defined by fat mass
were evaluated in a large, free living population. Out of a total of 29,235
subjects from the 2008-2010 Korean National Health and Nutrition Examination
Survey, the relevant data included 6458 subjects over 50 years of age who were
analyzed cross-sectionally. Serum 25OHD concentrations were compared in men (n =
3164) and in women (n = 3294) by tertiles of body weight and body fat mass, as
measured by Dual-energy X-ray Absorptiometry (DXA) within sex-specific tertiles
of body weight. Serum 25OHD was weakly inversely correlated with body weight in
the men and the women after adjustment for age (r = −0.075 and
−0.073, respectively, p < 0.001 for both). Within each tertile of body
weight, serum 25OHD decreased progressively as fat mass increased in men. This
pattern was similar in the women but not consistently significant. Whereas body
weight predicted a small decrease in serum 25OHD in the men and the women,
greater adiposity, for any given weight, predicted larger decreases in the men,
but not consistently in women.
PMID- 29966288
TI - Cellular and Subcellular Phosphate Transport Machinery in Plants.
AB - Phosphorus (P) is an essential element required for incorporation into several
biomolecules and for various biological functions; it is, therefore, vital for
optimal growth and development of plants. The extensive research on identifying
the processes underlying the uptake, transport, and homeostasis of phosphate (Pi)
in various plant organs yielded valuable information. The transport of Pi occurs
from the soil into root epidermal cells, followed by loading into the root xylem
vessels for distribution into other plant organs. Under conditions of Pi
deficiency, Pi is also translocated from the shoot to the root via the phloem.
Vacuoles act as a storage pool for extra Pi, enabling its delivery to the
cytosol, a process which plays an important role in the homeostatic control of
cytoplasmic Pi levels. In mitochondria and chloroplasts, Pi homeostasis regulates
ATP synthase activity to maintain optimal ATP levels. Additionally, the
endoplasmic reticulum functions to direct Pi transporters and Pi toward various
locations. The intracellular membrane potential and pH in the subcellular
organelles could also play an important role in the kinetics of Pi transport. The
presented review provides an overview of Pi transport mechanisms in subcellular
organelles, and also discusses how they affect Pi balancing at cellular, tissue,
and whole-plant levels.
PMID- 29966290
TI - Cynoglossus semilaevis Rspo3 Regulates Embryo Development by Inhibiting the
Wnt/beta-Catenin Signaling Pathway.
AB - Cynoglossus semilaevis is an important economic fish species and has long been
cultivated in China. Since the completion of its genome and transcriptome
sequencing, genes relating to C. semilaevis development have been extensively
studied. R-spondin 3 (Rspo3) is a member of the R-spondin family. It plays an
important role in biological processes such as vascular development and
oncogenesis. In this study, we cloned and characterized the expression patterns
and functions of C. semilaevisRspo3. Initial structural and phylogenetic analyses
revealed a unique FU3 domain that exists only in ray-finned fish RSPO3.
Subsequent embryonic expression profile analysis showed elevating expression of
Rspo3 from gastrulation to the formation of the eye lens, while, in tail bud
embryos, Rspo3 expression was significantly high in the diencephalon and
mesencephalon. The overexpression of C. semilaevis Rspo3 in Danio rerio embryos
resulted in a shortened rostral-caudal axis, edema of the pericardial cavity,
stubby yolk extension, and ecchymosis. Vascular anomalies were also observed,
which is consistent with Rspo3 role in vascular development. Drug treatment and a
dual-luciferase reporter assay confirmed the inhibitory role of C. semilaevis
Rspo3 in D. rerio Wnt/β-catenin signaling pathway. We further concluded that
the FU2, FU3, and TSP1 domains regulate the maternal Wnt/β-catenin signaling
pathway, while the FU1 domain regulates the zygotic Wnt/β-catenin signaling
pathway. This study enriches Rspo3 research in non-model animals and serves as
the basis for further research into the interactions between Rspo and the
Wnt/β-catenin signaling pathway.
PMID- 29966292
TI - Debonding Detection in Hidden Frame Supported Glass Curtain Walls Using the
Nonlinear Ultrasonic Modulation Method with Piezoceramic Transducers.
AB - Debonding defects are common and they are the main reason for the failure of
hidden frame supported glass curtain walls, which are widely used as an external
enclosure and decorative structure. In this paper, a debonding detection method
for hidden frame supported glass curtain walls is developed based on nonlinear
ultrasonic modulation and piezoceramic transducers. First, the excitation
frequency was determined according to the response characteristics. Then,
empirical mode decomposition (EMD) was applied to extract the feature components.
After discrete Fourier transform (DFT), the nonlinear coefficients were
calculated to evaluate the debonding defect. Finally, the experimental setup was
established and a series of experiments were carried out to verify the
feasibility and effectiveness of the nonlinear ultrasonic modulation method. The
nonlinear harmonics detection method was also investigated and it was compared
with the nonlinear ultrasonic modulation method. The detection effect at
different temperatures and impact were studied. The results showed that the
nonlinear coefficient increases with the debonding length. The mean squared error
(MSE) of the nonlinear ultrasonic modulation method was improved by 41% compared
with the nonlinear harmonics method. The nonlinear ultrasonic modulation method
can successfully detect debonding defects in hidden frame supported glass curtain
walls at different temperatures and impact.
PMID- 29966291
TI - Phosphoregulation of the Plant Cellulose Synthase Complex and Cellulose Synthase
Like Proteins.
AB - Cellulose, the most abundant biopolymer on the planet, is synthesized at the
plasma membrane of plant cells by the cellulose synthase complex (CSC). Cellulose
is the primary load-bearing polysaccharide of plant cell walls and enables cell
walls to maintain cellular shape and rigidity. The CSC is comprised of
functionally distinct cellulose synthase A (CESA) proteins, which are responsible
for synthesizing cellulose, and additional accessory proteins. Moreover, CESA
like (CSL) proteins are proposed to synthesize other essential non-cellulosic
polysaccharides that comprise plant cell walls. The deposition of cell-wall
polysaccharides is dynamically regulated in response to a variety of
developmental and environmental stimuli, and post-translational phosphorylation
has been proposed as one mechanism to mediate this dynamic regulation. In this
review, we discuss CSC composition, the dynamics of CSCs in vivo, critical
studies that highlight the post-translational control of CESAs and CSLs, and the
receptor kinases implicated in plant cell-wall biosynthesis. Furthermore, we
highlight the emerging importance of post-translational phosphorylation-based
regulation of CSCs on the basis of current knowledge in the field.
PMID- 29966293
TI - The Effects of Thiamine Tetrahydrofurfuryl Disulfide on Physiological Adaption
and Exercise Performance Improvement.
AB - Thiamine, named as vitamin B1, is an important cofactor for the critical enzymes
regarding to glucose metabolism, like transketolase, pyruvate dehydrogenase, and
alpha-ketoglutarate dehydrogenase. The thiamine tetrahydrofurfuryl disulfide
(TTFD) is a derivative of thiamine with higher bioavailability and solubility
than thiamine and has been widely applied to health maintenance and disease
therapy. Higher physical activities are associated with higher thiamine
supplements for efficient energy metabolism. Furthermore, the effective dose of
TTFD, beneficial to exercise physiological adaption and performance, still be
further validated and the safety evaluation were also an important issue to be
considered for potential application. ICR (Institute of Cancer Research) strain
mice were allocated as 0, 50, 100, and 500 mg/kg dose groups and administrated by
oral gavage consecutively for 6 weeks. Physical activities including grip
strength and aerobic endurance were measured. Various fatigue-associated
biochemical variables such as lactate, glucose, blood urine nitrogen (BUN) or
creatine kinase (CK), were also assessed. The levels of liver and muscle glycogen
were measured as an indicator of energy storage at the end of the experiment.
Toxicity assessments for long-term supplementation were also further evaluated
for safety consideration. TTFD supplementation significantly increased the
endurance and grip strength and demonstrated beneficial effects on lactate
production and clearance rate after an acute exercise challenge. The TTFD
supplementation significantly mitigated the BUN and CK indexes after extended
exercise and elevated the glycogen content in the liver and muscle tissues.
According to body composition, biochemical and histopathological data, daily
administration of TTFD for over 6 weeks (subacute toxicity) also demonstrated
reasonable safety results for long-term and adequate supplementation. The
toxicity of TTFD were also considered as safety for long-term supplementation
with indicated doses. Furthermore, the TTDF could be applied to not only the
health promotion but also improvement of exercise physiological adaption and the
TTFD could be further considered as potential ergogenic aids combined with
different nutrient strategy.
PMID- 29966294
TI - Lectin- and Saccharide-Functionalized Nano-Chemiresistor Arrays for Detection and
Identification of Pathogenic Bacteria Infection.
AB - Improvement upon, and expansion of, diagnostic tools for clinical infections have
been increasing in recent years. The simplicity and rapidity of techniques are
imperative for their adoption and widespread usage at point-of-care. The
fabrication and evaluation of such a device is reported in this work. The use of
a small bioreceptor array (based on lectin-carbohydrate binding) resulted in a
unique response profile, which has the potential to be used for pathogen
identification, as demonstrated by Principal Component Analysis (PCA). The
performance of the chemiresistive device was tested with Escherichia coli K12,
Enterococcus faecalis, Streptococcus mutans, and Salmonella typhi. The limits of
detection, based on concanavalin A (conA) lectin as the bioreceptor, are 4.7
× 103 cfu/mL, 25 cfu/mL, 7.4 × 104 cfu/mL, and 6.3 × 102
cfu/mL. This shows that the detection of pathogenic bacteria is achieved with
clinically relevant concentrations. Importantly, responses measured in spiked
artificial saliva showed minimal matrix interference. Furthermore, the
exploitation of the distinctive outer composition of the bacteria and selectivity
of lectin-carbohydrate interactions allowed for the discrimination of bacterial
infections from viral infections, which is a current and urgent need for
diagnosing common clinical infections.
PMID- 29966295
TI - Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes.
AB - Cytochrome P450 2J2 (CYP2J2) is a known arachidonic acid (AA) epoxygenase that
mediates the formation of four bioactive regioisomers of cis-epoxyeicosatrienoic
acids (EETs). Although its expression in the liver is low, CYP2J2 is mainly
observed in extrahepatic tissues, including the small intestine, pancreas, lung,
and heart. Changes in CYP2J2 levels or activity by xenobiotics, disease states,
or polymorphisms are proposed to lead to various organ dysfunctions. Several
studies have investigated the regulation of CYP2J2 and EET formation in various
cell lines and have demonstrated that such regulation is tissue-dependent. In
addition, studies linking CYP2J2 polymorphisms to the risk of developing
cardiovascular disease (CVD) yielded contradictory results. This review will
focus on the mechanisms of regulation of CYP2J2 by inducers, inhibitors, and
oxidative stress modeling certain disease states in various cell lines and
tissues. The implication of CYP2J2 expression, polymorphisms, activity and, as a
result, EET levels in the pathophysiology of diabetes and CVD will also be
discussed.
PMID- 29966296
TI - Design, Synthesis, and Evaluation of Homochiral Peptides Containing Arginine and
Histidine as Molecular Transporters.
AB - Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine
and histidine residues were synthesized. The peptides showed 0-15% cytotoxicity
at 5-100 µM in human ovarian adenocarcinoma (SK-OV-3) cells while they
exhibited 0-12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all
peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell
impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of
different alkyl chain length were attached at the N-terminal of the linear
peptide (HR)4 to improve the molecular transporter property. Addition of fatty
acyl chains was expected to help with the permeation of the peptides through the
cell membrane. Thus, we synthesized seven fatty acyl derivatives of the linear
(HR)4 peptide. The peptides were synthesized using Fmoc/tBu solid phase peptide
chemistry, purified by reverse-phase high-performance liquid chromatography (RP
HPLC) and characterized by matrix-assisted laser desorption/ionization (MALDI)
spectrometry. The fatty acyl peptides containing C8, C12, C14, and C18 alkyl
chain did not show cytotoxicity on SK-OV-3 or CCRF-CEM cell lines up to 50
µM concentration; however, at higher concentration (100 µM), they
showed mild cytotoxicity. For example, C16-(HR)4 was also found to reduce the
proliferation of SK-OV-3 cells by 11% at 50 µM and C20-(HR)4 showed mild
toxicity at 10 µM, reducing the proliferation of SK-OV-3 cells by 21%.
Increase in the length of alkyl chain showed cytotoxicity to the cell lines. C20
(HR)4 peptide showed better efficiency in translocation of F′-GpYEEI to SK
OV-3 than the phosphopeptide alone. Further investigation of C20-(HR)4 peptide
efficacy showed that the peptide could deliver doxorubicin and epirubicin into SK
OV-3 and also improved the drug antiproliferative ability. These studies provided
insights into understanding the structural requirements for optimal cellular
delivery of the fatty acyl-(HR)4 peptide conjugates.
PMID- 29966297
TI - An Unusual and Fatal Cause of Miliary Nodules on Chest Radiography.
AB - Foreign body granulomatosis has many etiologies, including the injection of oral
medications intravenously. The insoluble filler materials that are used in the
medications can lodge in pulmonary arterioles and capillaries, which can trigger
foreign body giant cell reaction, chronic inflammation, thrombosis, and fibrosis,
resulting in pulmonary hypertension, progressive shortness of breath, and,
potentially, fatal conditions. On imaging, this may present with multiple miliary
mottling’s/nodules. The use of a bronchoscopy with biopsy can be an
excellent way to establish a diagnosis in appropriate clinical settings. Here, we
present a case of a 37-year-old old male found to have multiple miliary densities
on imaging due to intravenous use of oral medication.
PMID- 29966298
TI - The Roles of DNA Topoisomerase IIbeta in Transcription.
AB - Type IIA topoisomerases allow DNA double helical strands to pass through each
other by generating transient DNA double strand breaks βDSBs), and in so
doing, resolve torsional strain that accumulates during transcription, DNA
replication, chromosome condensation, chromosome segregation and recombination.
Whereas most eukaryotes possess a single type IIA enzyme, vertebrates possess two
distinct type IIA topoisomerases, Topo IIα and Topo IIβ. Although the
roles of Topo IIα, especially in the context of chromosome condensation and
segregation, have been well-studied, the roles of Topo IIβ are only
beginning to be illuminated. This review begins with a summary of the initial
studies surrounding the discovery and characterization of Topo IIβ and then
focuses on the insights gained from more recent studies that have elaborated
important functions for Topo IIβ in transcriptional regulation.
PMID- 29966300
TI - Australian Public Opinions Regarding the Live Export Trade before and after an
Animal Welfare Media Expose.
AB - The long distance export of livestock from Australia to Asia has long aroused
controversy for suspected animal welfare concerns during and after the voyage.
However, there is little or no information on the attitude of the Australian
public towards this trade. A total of 522 Australians were surveyed in Brisbane
to find out about their understanding of the trade, their attitudes towards it
and the influence of demographic factors. Approximately one half of respondents
were surveyed just before a media exposé of cruelty on sheep shipments in
2017 from Australia to the Middle East and one half just after the exposé,
to see the impact of media depiction of cruel treatment of live export sheep.
Most respondents believed that they were familiar with the industry, and more
after the media exposé than before. More respondents had negative than
positive feelings about the trade, and just over a quarter had no feelings. Twice
as many thought it should be ended than maintained, particularly women, but 40%
said that it depends, mainly on ethics and animal-based reasons. Those that
thought it should not be ended mainly did so to support farmers and the
country’s economy. Almost one half had seen the media exposé,
particularly older respondents, and expressions of sadness, empathy for the
animals and anger were the most common responses to such footage. Although it
increased the number of people saying that they were familiar with the trade, it
did not affect people’s view of the trade, except that fewer indicated that
ending the trade was dependent on other factors. It is concluded that the
majority of Australian respondents in one capital city had negative views towards
the live export trade, and that a media exposé had some influence on this
view.
PMID- 29966299
TI - Physical Activity and Physical Fitness of Adults with Intellectual Disabilities
in Group Homes in Hong Kong.
AB - Adults with intellectual disabilities (ID) typically have a sedentary lifestyle
and higher rates of overweight and obesity. This study describes the habitual
daily physical activity (PA) and the health-related physical fitness (PF) of
adults with mild and moderate ID who resided in four group homes and worked in
sheltered workshops. We also assessed the contribution of PF variables towards PA
levels and sedentary behavior of this population subgroup. Adults with mild and
moderate ID (N = 114) were assessed on PF tests (percent body fat, waist and hip
circumferences, 6-min walk (6MWT), arm curl, and sit and reach). PA and sedentary
behavior on weekdays were determined using Actigraph accelerometers. Results
showed these adults averaged 2% of their daily time (or 10 min) engaged in
moderate-to-vigorous PA (MVPA) and 67% of the time (495 min) being sedentary. No
significant differences between mild and moderate ID were found for any PA or PF
variable. Linear multiple regression analyses showed 6MWT to be the only
significant PF variable contributing to the variance of PA and sedentary
behavior. In conclusion, adults with ID reside in group home have low PA and low
fitness levels. Among fitness variables, the walking test (i.e., cardiovascular
fitness) had the highest positive association with participants’ daily PA,
MVPA, and negative association with sedentary behavior. Future intervention
studies in promoting PA and fitness for adults with ID are warranted.
PMID- 29966301
TI - Electromechanical Response of High-Performance Fiber-Reinforced Cementitious
Composites Containing Milled Glass Fibers under Tension.
AB - The self-damage sensing capacity of high-performance fiber-reinforced
cementitious composites (HPFRCCs) that blended long- (1 vol %) and medium-length
(1 vol %) smooth steel fibers was considerably improved by adding milled glass
fibers (MGFs) with a low electrical conductivity to a mortar matrix. The addition
of MGFs (5 wt %) significantly increased the electrical resistivity of the mortar
matrix from 45.9 to 110.3 kΩ·cm (140%) and consequently improved the
self-damage sensing capacity (i.e., the reduction in the electrical resistivity
during the tensile strain-hardening response) from 17.27 to 25.56
kΩ·cm (48%). Furthermore, the addition of MGFs improved the
equivalent bond strength of the steel fibers on the basis of the higher pullout
energy owing to the accumulated cementitious material particles attached to the
surfaces of steel fibers.
PMID- 29966302
TI - Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic
Cells.
AB - Innate and adaptive immune cells from myeloid and lymphoid lineages resolve host
infection or cell stress by mounting an appropriate and durable immune response.
Upon sensing of cellular insults, immune cells become activated and undergo rapid
and efficient functional changes to unleash biosynthesis of macromolecules,
proliferation, survival, and trafficking; unprecedented events among other
mammalian cells within the host. These changes must become operational within
restricted timing to rapidly control the insult and to avoid tissue damage and
pathogen spread. Such changes occur at high energy cost. Recent advances have
established that plasticity of immune functions occurs in distinct metabolic
stress features. Evidence has accumulated to indicate that specific metabolic
signatures dictate appropriate immune functions in both innate and adaptive
immunity. Importantly, recent studies have shed light on whether successfully
manipulating particular metabolic targets is sufficient to modulate immune
function and polarization, thereby offering strong therapeutic potential for
various common immune-mediated diseases, including inflammation and autoimmune
associated diseases and cancer. In this review, we detail how cellular metabolism
controls immune function and phenotype within T cells and macrophages
particularly, and the distinct molecular metabolic programming and targets
instrumental to engage this regulation.
PMID- 29966304
TI - A Robust Bioimpedance Structure for Smartwatch-Based Blood Pressure Monitoring.
AB - One potential method to estimate noninvasive cuffless blood pressure (BP) is
pulse wave velocity (PWV), which can be calculated by using the distance and the
transit time of the blood between two arterial sites. To obtain the pulse
waveform, bioimpedance (BI) measurement is a promising approach because it
continuously reflects the change in BP through the change in the arterial cross
sectional area. Many studies have investigated BI channels in a vertical
direction with electrodes located along the wrist and the finger to calculate PWV
and convert to BP; however, the measurement systems were relatively large in
size. In order to reduce the total device size for use in a PWV-based BP
smartwatch, this study proposed and examined a robust horizontal BI structure.
The BI device was also designed to apply in a very small body area. The proposed
structure was based on two sets of four electrodes attached around the wrist. Our
model was evaluated on 15 human subjects; the PWV values were obtained with
various distances between two BI channels to assess the efficacy. The results
showed that the designed BI system can monitor pulse rate efficiently in only a
0.5 × 1.75 cm2 area of the body. The correlation of pulse rate from the
proposed design against the reference was 0.98 +/- 0.07 (p < 0.001). Our
structure yielded higher detection ratios for PWV measurements of 99.0 +/- 2.2%,
99.0 +/- 2.1%, and 94.8 +/- 3.7% at 1, 2, and 3 cm between two BI channels,
respectively. The measured PWVs correlated well with the BP standard device at
0.81 +/- 0.08 and 0.84 +/- 0.07 with low root-mean-squared-errors at 7.47 +/-
2.15 mmHg and 5.17 +/- 1.81 mmHg for SBP and DBP, respectively. The result
demonstrates the potential of a new wearable BP smartwatch structure.
PMID- 29966306
TI - Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor
and Retinoic Acid Receptor alpha in Human Acute Myeloid Leukemia Cell Lines.
AB - All-trans-retinoic acid (ATRA) and 1α,25-dihydroxyvitamin D (1,25D) are
potent inducers of differentiation of myeloid leukemia cells. During myeloid
differentiation specific transcription factors are expressed at crucial
developmental stages. However, precise mechanism controlling the diversification
of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP)
transcription factors have been characterized as key regulators of the
development and function of the myeloid system. Past data point at functional
redundancy among C/EBP family members during myeloid differentiation. In this
study, we show that in acute myeloid leukemia (AML) cells, high expression of
vitamin D receptor gene (VDR) is needed for strong and sustained upregulation of
CEBPB gene, while the moderate expression of VDR is sufficient for upregulation
of CEBPD in response to 1,25D. The high expression level of the gene encoding for
retinoic acid receptor α (RARA) allows for high and sustained expression of
CEBPB, which becomes decreased along with a decrease of RARA expression.
Expression of CEBPB induced by ATRA is accompanied by upregulated expression of
CEBPE with similar kinetics. Our results suggest that CEBPB is the major VDR and
RARA-responsive gene among the CEBP family, necessary for expression of genes
connected with myeloid functions.
PMID- 29966305
TI - Establishing a Dedicated Lung Cancer Biobank at the University Center Hospital of
Nice (France). Why and How?
AB - Lung cancer is the major cause of death from cancer in the world and its
incidence is increasing in women. Despite the progress made in developing
immunotherapies and therapies targeting genomic alterations, improvement in the
survival rate of advanced stages or metastatic patients remains low. Thus, urgent
development of effective therapeutic molecules is needed. The discovery of novel
therapeutic targets and their validation requires high quality biological
material and associated clinical data. With this aim, we established a biobank
dedicated to lung cancers. We describe here our strategy and the indicators used
and, through an overall assessment, present the strengths, weaknesses,
opportunities and associated risks of this biobank.
PMID- 29966307
TI - Is Nature Relatedness Associated with Better Mental and Physical Health?
AB - Nature relatedness is a psychological characteristic with the potential to drive
interaction with nature and influence well-being. We surveyed 1538 people in
Brisbane, Australia to investigate how nature relatedness varies among socio
demographic groups. We determined whether people with higher nature relatedness
reported fewer symptoms of depression, anxiety, stress and better overall health,
controlling for potentially confounding socio-demographic and health-related
variables. Overall nature relatedness was higher in older people, females, those
without children living at home, not working, and people speaking English at
home. Aspects of nature relatedness reflecting enjoyment of nature were
consistently associated with reduced ill health, consistent with widespread
evidence of the health and well-being benefits of experiencing nature. In
contrast, aspects of nature relatedness reflecting self-identification with
nature, and a conservation worldview, were associated with increased depression,
anxiety or stress, after accounting for potential confounding factors. Detailed
investigation of causal pathways among nature relatedness, socio-demographic
factors and health is warranted, with particular focus on the relationship
between stress and nature orientation.
PMID- 29966303
TI - Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and
Challenges.
AB - Tissue engineering is a promising approach to repair tendon and muscle when
natural healing fails. Biohybrid constructs obtained after cells’ seeding
and culture in dedicated scaffolds have indeed been considered as relevant tools
for mimicking native tissue, leading to a better integration in vivo. They can
also be employed to perform advanced in vitro studies to model the cell
differentiation or regeneration processes. In this review, we report and analyze
the different solutions proposed in literature, for the reconstruction of tendon,
muscle, and the myotendinous junction. They classically rely on the three pillars
of tissue engineering, i.e., cells, biomaterials and environment (both chemical
and physical stimuli). We have chosen to present biomimetic or bioinspired
strategies based on understanding of the native tissue
structure/functions/properties of the tissue of interest. For each tissue, we
sorted the relevant publications according to an increasing degree of complexity
in the materials’ shape or manufacture. We present their biological and
mechanical performances, observed in vitro and in vivo when available. Although
there is no consensus for a gold standard technique to reconstruct these musculo
skeletal tissues, the reader can find different ways to progress in the field and
to understand the recent history in the choice of materials, from collagen to
polymer-based matrices.
PMID- 29966308
TI - Technology-Enhanced Classroom Activity Breaks Impacting Children's Physical
Activity and Fitness.
AB - BACKGROUND: This study examined the effects of a 4-week technology-enhanced
physical activity (PA) interventions on students’ real-time daily PA and
aerobic fitness levels. METHODS: 116 fifth-graders were assigned to one
intervention group (n = 31) participating in daily physical activity engaging the
brain with Fitbit Challenge (PAEB-C), another intervention group (n = 29) wearing
Fitbits only (Fitbit-O) daily, five days per week, or the comparison group (n =
56). Four-week real-time PA data were collected from the intervention students
via Fitbase. Three groups were pre- and post-tested aerobic fitness. RESULTS: The
PAEB-C students showed significantly higher steps and minutes of being very
active and fairly active (F = 7.999, p = 0.014, n = 0.121; F = 5.667, p = 0.021,
n = 0.089; F = 10.572, p = 0.002, n = 0.154) and lower minutes of being sedentary
daily (F = 4.639, p = 0.035, n = 0.074) than the Fitbit-O group. Both Fitbit
groups exhibited significantly greater increases in aerobic fitness scores than
the comparison group over time (F = 21.946, p = 0.001, n = 0.303). Boys were more
physically active and fit than girls. CONCLUSIONS: Technology-enhanced PA
intervention was effective for improving real-time PA and aerobic fitness.
PMID- 29966309
TI - A Computational Model of Watermark Algorithmic Robustness Capable of Resisting
Image Cropping for Remote Sensing Images.
AB - Various watermarking algorithms have been studied to better enable the copyright
protection of remote sensing images. The robustness of such algorithms against
image cropping attacks has subsequently been verified mainly by various
experiments. However, to date, the experimental results are subject to the
differences in experimental factors and computational resource costs. Hence, the
study presented in this paper proposes a robustness computation model of
watermarking remote sensing images in terms of the image cropping attack. The
robustness computation model consists of three parts: analysis principles, an
evaluation index, and a computation method. The robustness analysis principles
are provided based on the salient features of watermarking remote sensing images
and attacking properties. A probability-based evaluation index is then defined to
more comprehensively measure the robustness of different algorithms. The
computation method developed in this study is based on permutations and the
inclusion-exclusion principle to theoretically calculate robustness. The
experiments conducted to verify the effectiveness of the computation model,
revealed true closeness between both the calculated and experimental results.
Finally, the relationships between the robustness and the different parameters
used in the watermarking algorithms are investigated by using the proposed
computation model.
PMID- 29966310
TI - Structure and Properties of Zr-Based Bulk Metallic Glasses in As-Cast State and
After Laser Welding.
AB - Laser-beam fusion welding processes enable the increase of the size of metallic
glass parts, and therefore facilitate the application of this new material in
different products. To get exceptional properties of the material after the
welding process, characteristics of the weld structure in the heat affected zone
and in the fusion zone should be predicted. The main goal of this work is to
study the structure and specific characteristics of the Zr55Cu30Ni5Al10 alloy
after the casting process and after the laser welding process. Electron
microscopy observation confirmed that the amorphous phase was present in the
fusion zone and amorphous-crystalline phase was present in the heat-affected
zone. Higher nanohardness and reduced Young’s modulus values were
demonstrated for laser welds using higher impulse energy (2.78 J) and impulse
peak power (1000 W).
PMID- 29966311
TI - Dynamics of p14ARF and Focal Adhesion Kinase-Mediated Autophagy in Cancer.
AB - It has been widely shown that the focal adhesion kinase (FAK) is involved in
nearly every aspect of cancer, from invasion to metastasis to epithelial
mesenchymal transition and maintenance of cancer stem cells. FAK has been shown
to interact with p14ARF (alternative reading frame)—a well-established
tumor suppressor—and functions in the negative regulation of cancer through
both p53-dependent and -independent pathways. Interestingly, both FAK and ARF
(human and mouse counterpart) proteins, as well as p53, are involved in
autophagy—a process of “self-digestion”—whose main
function is the recycling of cellular components and quality control of proteins
and organelles. In the last years, an unexpected role of p14ARF in the survival
of cancer cells has been underlined in different cellular contexts, suggesting a
novel pro-oncogenic function of this protein. In this review, the mechanisms
whereby ARF and FAK control autophagy are presented, as well as the role of
autophagy in cell migration and spreading. Integrated investigation of these cell
functions is extremely important to understand the mechanism of the basis of cell
transformation and migration and thus cancer development.
PMID- 29966312
TI - Single Nucleotide Polymorphisms in the Vitamin D Receptor Gene (VDR) May Have an
Impact on Acute Pancreatitis (AP) Development: A Prospective Study in Populations
of AP Patients and Alcohol-Abuse Controls.
AB - Vitamin D imbalance is suggested to be associated with the development of
pancreatitis. Single nucleotide polymorphisms (SNPs), Apa-1, Bsm-1, Fok-1, and
Taq-1, in the vitamin D receptor gene (VDR) are known in various diseases, but
not yet in pancreatitis. The aim of this study was to explore possible
associations of the four SNPs in the VDR receptor gene in a population of acute
pancreatitis patients and alcohol-abuse controls, and to investigate the
association with acute pancreatitis (AP) susceptibility. The study population (n
= 239) included acute pancreatitis patients (n = 129) and an alcohol-abuse
control group (n = 110). All patients met the Diagnostic and Statistical Manual
of Mental Disorders (DSM IV) criteria for alcohol dependence. DNA was extracted
from peripheral leukocytes and analyzed for VDR polymorphisms using a polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odd
ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic
regression analysis. To date, we have found allele T in Taq-1 (OR = 2.61; 95% CI:
1.68-4.03; p < 0.0001) to be almost three times more frequent in the AP group
compared to the alcohol-abuse control patients. Polymorphism Taq-1 occurring in
the vitamin D receptor may have an impact on the development of acute
pancreatitis due to the lack of the protective role of vitamin D.
PMID- 29966313
TI - Effects of Dance Movement Therapy on Adult Patients with Autism Spectrum
Disorder: A Randomized Controlled Trial.
AB - This study examines the effects of dance movement therapy (DMT) on empathy for
adults with autism spectrum disorder (ASD). DMT based on the embodiment approach
offers body-centered interventions, such as mirroring techniques, to address the
needs of ASD patients. Accordingly, findings of a feasibility study suggest that
DMT may be an effective approach for clients on the ASD spectrum. The present
study is a randomized controlled trial that was conducted as a multicenter study
within the framework of the EU-funded research project TESIS (Toward an Embodied
Science of Intersubjectivity), and employed a two-factorial between-subject
design. The treatment group (n = 35) participated in a 10-week manualized DMT
intervention, whereas the control group (n = 22) received treatment only after a
waiting period. Empathy, measured with the Cognitive and Emotional Empathy
Questionnaire (CEEQ), was the main variable of interest, analyzed by a repeated
measures analysis of variance. In order to also include incomplete data cases, we
used the expectation-maximization algorithm for missing data estimation. Results
suggest no significant changes in overall empathy between groups. We discuss the
results and limitations, as well as future research options.
PMID- 29966315
TI - Fat Intake Reduction Strategies among Children and Adults to Eliminate Obesity
and Non-Communicable Diseases in the Eastern Mediterranean Region.
AB - Non-communicable diseases (NCDs) are the leading cause of mortality globally with
an estimated 39.5 million deaths per year (72% of total death) in 2016, due to
the four major NCDs: cardiovascular diseases, cancers, chronic respiratory
diseases and diabetes. In the Eastern Mediterranean Region (EMR), almost 68% of
all deaths are attributed to NCDs commonly known as chronic or lifestyle-related
diseases. Two-thirds of NCD premature deaths are linked to 4 shared modifiable
behavioral risk factors: tobacco use, unhealthy diet, physical inactivity and
harmful use of alcohol. These unhealthy behaviours lead to 4 key
metabolic/biological changes; raised blood pressure, overweight/obesity, high
blood glucose levels/diabetes, and hyperlipidemia (high levels of fat in the
blood), that increase the risk of NCDs. Globally, countries are already working
towards agreed global goals on maternal and infant nutrition and on the
prevention of NCDs. In both fields the goals include halting the increase in
overweight and obesity and reducing NCD diet-related risk factors including
reducing saturated fatty acids (SFAs) and trans fatty acids (TFAs) intake. The
objective of this review is to present an up-to-date overview of the current fat
(SFAs and TFAs) intake reduction initiatives in countries of the Eastern
Mediterranean Region (EMR) by highlighting national and regional programs,
strategies and activities aiming at decreasing the intakes of dietary fat (SFA
and TFA). The literature review shows that the average intake of SFA is estimated
to be 10.3% of the total energy intake (EI), exceeding the WHO (World Health
Organization) upper limit of 10%. The average TFA intake is estimated at 1.9% EI,
which also exceeds the WHO upper limit of 1% EI. The highest SFAs intake was
reported from Djibouti, Kuwait, Saudi-Arabia, Lebanon and Yemen, while the
highest TFAs intakes were reported from Egypt and Pakistan. If countries of the
EMR receive immediate public health attention, that toll of NCD-related morbidity
and mortality would be considerably decreased through the implantation of
evidence-based preventive interventions. In this context, reductions in SFAs and
TFAs intakes have been highlighted as cost-effectives strategies that may hamper
the growth of the NCD epidemic.
PMID- 29966316
TI - Protein Hydrolysates' Absorption Characteristics in the Dynamic Small Intestine
In Vivo.
AB - : Background: Dietary proteins are known for their wide range of nutritional,
functional and biological properties. Although the total amount of proteins may
be obtained from mixtures, its "availability" for absorption in the gut is in
many cases quite uncertain or even varies for the same food depending on
processing conditions, the presence of other components, and so on. Methods: To
obtain accurate protein hydrolysate absorption data, we have developed a small
intestine model (SIM) to test them. Results: The results indicated that the
protein hydrolysates were absorbed rapidly during the first 15 min, and then
decreased to 90 min, then they were absorbed again from 90 min to the endpoint.
The protein absorption was also affected by the protein processing method used.
The Enzyme + Ultrasound (EU) processing method group had a higher absorption rate
than the Enzyme (E) processing method group, and the absorption of the Enzyme +
Artificial gastric juice processing method (EH) and Enzyme + Ultrasound +
Artificial gastric juice processing method (EUH) groups was reduced compared to
the E group alone. The amino acid analysis results showed that the amino acids
were reduced and absorbed by our SIM in almost all groups except for cysteine and
methionine. In general, the Pearson relation value of the amino acid contents
between before SIM and after SIM was 0.887, which indicated that single amino
acid absorption was mainly related to its content in the whole amino acids. The
single amino acid absorption ratio among different groups also displayed
differences, which ranged from 31% to 46% (E group from 39% to 42%; EU group from
40% to 47%; EH group from 31% to 39%; EUH group from 35% to 41%). CONCLUSIONS:
The protein hydrolysates' varied from startpoint to endpoint, and the protein
absorption was affected by processing method.
PMID- 29966314
TI - Prospective Associations between Single Foods, Alzheimer's Dementia and Memory
Decline in the Elderly.
AB - Background: Evidence whether single “cognitive health” foods could
prevent cognitive decline is limited. We investigated whether dietary intake of
red wine, white wine, coffee, green tea, olive oil, fresh fish, fruits and
vegetables, red meat and sausages, assessed by a single-food-questionnaire, would
be associated with either incident Alzheimer’s dementia (AD) or verbal
memory decline. Methods: Participants aged 75+ of the German Study on Aging,
Cognition and Dementia in Primary Care Patients (AgeCoDe) cohort were regularly
followed over 10 years (n = 2622; n = 418 incident AD cases). Multivariable
adjusted joint modeling of repeated-measures and survival analysis was used,
taking gender and Apolipoprotein E4 (APOE ε4) genotype into account as
possible effect modifiers. Results: Only higher red wine intake was associated
with a lower incidence of AD (HR = 0.92; P = 0.045). Interestingly, this was true
only for men (HR = 0.82; P < 0.001), while in women higher red wine intake was
associated with a higher incidence of AD (HR = 1.15; P = 0.044), and higher white
wine intake with a more pronounced memory decline over time (HR = −0.13; P
= 0.052). Conclusion: We found no evidence for these single foods to be
protective against cognitive decline, with the exception of red wine, which
reduced the risk for AD only in men. Women could be more susceptible to
detrimental effects of alcohol.
PMID- 29966318
TI - Novel 2-Thioxanthine and Dipyrimidopyridine Derivatives: Synthesis and
Antimicrobial Activity.
AB - The authors wish to make the following changes to their paper [1].[...].
PMID- 29966319
TI - Nature of Excitons in Bidimensional WSe2 by Hybrid Density Functional Theory
Calculations.
AB - 2D tungsten diselenide (2D-WSe2) is one of the most successful bidimensional
materials for optoelectronic and photonic applications, thanks to its strong
photoluminescence properties and to a characteristic large exciton binding
energy. Although these optical properties are widely recognized by the scientific
community, there is no general understanding of the atomistic details of the
excitonic species giving rise to them. In this work, we present a density
functional theory investigation of excitons in 2D-WSe2, where we compare results
obtained by standard generalized gradient approximation (GGA) methods (including
spin-orbit coupling) with those by hybrid density functionals. Our study provides
information on the size of the self-trapped exciton, the number and type of atoms
involved, the structural reorganization, the self-trapping energy, and the
photoluminescence energy, whose computed value is in good agreement with
experimental measurements in the literature. Moreover, based on the comparative
analysis of the self-trapping energy for the exciton with that for isolated
charge carriers (unbound electrons and holes), we also suggest a simplified
approach for the theoretical estimation of the excitonic binding energy, which
can be compared with previous estimates from different approaches or from
experimental data.
PMID- 29966317
TI - Molecular Cloning and Effects of Tm14-3-3zeta-Silencing on Larval Survivability
Against E. coli and C. albicans in Tenebrio molitor.
AB - The 14-3-3 family of proteins performs key regulatory functions in
phosphorylation-dependent signaling pathways including cell survival and
proliferation, apoptosis, regulation of chromatin structure and autophagy. In
this study, the zeta isoform of 14-3-3 proteins (designated as Tm14-3-3ζ)
was identified from the expressed sequence tags (ESTs) and RNA sequencing (RNA
Seq) database of the coleopteran pest, Tenebrio molitor. Tm14-3-3ζ messenger
RNA (mRNA) is expressed at higher levels in the immune organs of the larval and
adult stages of the insect and exhibit almost five-fold induction within 3 h post
infection of the larvae with Escherichia coli and Candida albicans. To
investigate the biological function of Tm14-3-3ζ, a peptide-based Tm14-3
3ζ polyclonal antibody was generated in rabbit and the specificity was
confirmed using Western blot analysis. Immunostaining and confocal microscopic
analyses indicate that Tm14-3-3ζ is mainly expressed in the membranes of
midgut epithelial cells, the nuclei of fat body and the cytosol of hemocytes.
Gene silencing of Tm14-3-3ζ increases mortality of the larvae at 7 days post
infection with E. coli and C. albicans. Our findings demonstrate that 14-3
3ζ in T. molitor is essential in the host defense mechanisms against
bacteria and fungi.
PMID- 29966320
TI - On the Performance of Thin-Walled Crash Boxes Joined by Forming.
AB - A new joining by forming process that combines lancing and shearing with sheet
bulk compression is utilized to assemble thin-walled crash boxes utilized as
energy absorbers. Process design and fabrication of the new crash boxes are
analyzed by finite elements and experimentation. Axial crush tests were performed
to compare the overall crashworthiness performance of the new crash boxes against
that of conventional crash boxes assembled by resistance spot-welding. Results
show that the joining process is a good alternative to resistance spot-welding
because the new crash boxes can absorb the same crushing energy, and because the
new process helps to overcome typical manufacturing problems of welding.
PMID- 29966321
TI - A Semi-Supervised Approach to Bearing Fault Diagnosis under Variable Conditions
towards Imbalanced Unlabeled Data.
AB - Fault diagnosis of rolling element bearings is an effective technology to ensure
the steadiness of rotating machineries. Most of the existing fault diagnosis
algorithms are supervised methods and generally require sufficient labeled data
for training. However, the acquisition of labeled samples is often laborious and
costly in practice, whereas there are abundant unlabeled samples which also imply
health information of bearings. Thus, it is worthwhile to develop semi-supervised
methods of fault diagnosis to make effective use of the plentiful unlabeled
samples. Nevertheless, considering the normal data are much more than the faulty
ones, the problem of imbalanced data exists among unlabeled samples for fault
diagnosis. Besides, in practice, bearings often work under uncertain and variable
operation conditions, which would also have negative influence on fault
diagnosis. To solve these issues, a novel hybrid method for bearing fault
diagnosis is proposed in this paper: (1) Inspired by visibility graph, a novel
fault feature extraction method named visibility graph feature (VGF) is proposed.
The obtained features by VGF are natively insensitive to variable conditions,
which has been validated by a simulation experiment in this paper; (2) On basis
of VGF, to deal with imbalanced unlabeled data, graph-based rebalance semi
supervised learning (GRSSL) for fault diagnosis is proposed. In GRSSL, a graph
based on a weighted sparse adjacency matrix is constructed by the k-nearest
neighbors and Gaussian Kernel weighting algorithm by means of the samples. Then,
a bivariate cost function over classification and normalized label variable is
built up to rebalance the importance of labels. Finally, the proposed VGF-GRSSL
method was verified by data collected from Case Western Reserve University
Bearing Data Center. The experiment results show that the proposed method of
bearing fault diagnosis performs effectively to deal with the imbalanced
unlabeled data under variable conditions.
PMID- 29966322
TI - When Control Exacerbates Distress: A Qualitative Study Exploring the Experiences
of Hong Kong Chinese Parents in Caring for a Child with Asthma.
AB - Background: Many parents have difficulty managing childhood asthma. In Hong Kong
(HK), while medication is the primary form of treatment, traditional Chinese
medicine is another favored option. In addition, HK follows a dual-track
healthcare system, which may pose unique experiences for Chinese parents in
managing childhood asthma. This qualitative descriptive study aimed to explore
the experiences of HK Chinese parents in caring for their children with asthma.
Methods: Fourteen HK Chinese mothers of children (aged 3-10) suffering from
asthma were purposively sampled to participate in individual, semi-structured
interviews. A realist approach following conventional content analysis was used
to interpret the interviews. Results: The mothers expressed feelings of
uncertainty, fear of asthma crises, and searched for ways to cope. As long as
their child’s asthma symptoms recurred, the mothers’ distress
continued. Their distress was sometimes exacerbated by self-doubt and worries
over whether they would receive adequate support from their family and healthcare
professionals. Conclusions: Helping parents to understand their limits may help
them be more open to varied aspects of their caregiving experiences, and thus to
cope better. Psychological interventions together with traditional educational
training may help to alleviate the psychological difficulties of parents.
PMID- 29966323
TI - Management of Primary and Recurrent Clostridium difficile Infection: An Update.
AB - BACKGROUND: Clostridium difficile infection (CDI) is one of the most common
healthcare-associated infections (HAI) in the United States and Canada, and
incidence rates have increased worldwide in recent decades. Currently,
antibiotics are the mainstay treatments for both primary and recurrent CDI, but
their efficacy is limited, prompting further therapies to be developed. Aim: This
review summarizes current and emerging therapies in CDI management including
antibiotics, fecal microbiota transplantation, monoclonal antibodies, spore-based
therapies, and vaccinations.
PMID- 29966324
TI - The Use of Antidepressive Agents and Bone Mineral Density in Women: A Meta
Analysis.
AB - Antidepressive agents are one of the fastest-growing classes of prescribed drugs.
However, the effects of antidepressive agents on bone density are controversial.
The aim of this meta-analysis is to evaluate the state of research on the
relationship between the use of tricyclic antidepressants (TCAs) or selective
serotonin reuptake inhibitors (SSRIs) and bone mineral density (BMD) in women.
The database searched was Pubmed. The meta-analysis included human studies in
women fulfilling the following criteria: (i) an assessment of bone mineral
density in the lumbar spine, the femoral neck or the total hip; (ii) a comparison
of the BMD of depressed individuals using antidepressive agents (SSRIs or TCAs),
and a control group that did not use antidepressive agents; (iii) measurement of
BMD using dual-energy X-ray absorptiometry (DXA); and (iv) calculations of the
mean BMD and standard deviation or standard error. Four studies were identified,
which, in total, included 934 women using antidepressive agents and 5767 non
using individuals. The results showed that no significant negative composite
weighted mean effect sizes were identified for the comparisons between SSRI users
and non-users. Similarly, no significant negative composite weighted mean effect
sizes were identified for the comparisons between TCA users and non-users,
indicating similar BMD in SSRI or TCA users and non-users. The meta-analysis
shows that the association between antidepressant medication and bone mineral
density has not been extensively researched. Only four studies fulfilled the
inclusion criteria. The global result of the literature review and meta-analysis
was that the use of antidepressive agents was not associated with lower or higher
BMD. This result applies to both SSRIs and TCAs and to all measurement locations
(lumbar spine, femoral neck and total hip).
PMID- 29966325
TI - A Photophysical Deactivation Channel of Laser-Excited TATB Based on Semiclassical
Dynamics Simulation and TD-DFT Calculation.
AB - A deactivation channel for laser-excited 1,3,5-triamino-2,4,6-trinitrobenzene
(TATB) was studied by semiclassical dynamics. Results indicate that the excited
state resulting from an electronic transition from the highest occupied molecular
orbital (HOMO) to the lowest unoccupied molecular mrbital (LUMO) is deactivated
via pyramidalization of the activated N atom in a nitro group, with a lifetime of
2.4 ps. An approximately 0.5-electron transfer from the aromatic ring to the
activated nitro group led to a significant increase of the C-NO2 bond length,
which suggests that C-NO2 bond breaking could be a trigger for an explosive
reaction. The time-dependent density functional theory (TD-DFT) method was used
to calculate the energies of the ground and S1 excited states for each
configuration in the simulated trajectory. The S1←S0 energy gap at the
instance of non-adiabatic decay was found to be 0.096 eV, suggesting that the
decay geometry is close to the conical intersection.
PMID- 29966326
TI - A hnRNP K-AR-Related Signature Reflects Progression toward Castration-Resistant
Prostate Cancer.
AB - The major challenge in castration-resistant prostate cancer (CRPC) remains the
ability to predict the clinical responses to improve patient selection for
appropriate treatments. The finding that androgen deprivation therapy (ADT)
induces alterations in the androgen receptor (AR) transcriptional program by AR
coregulators activity in a context-dependent manner, offers the opportunity for
identifying signatures discriminating different clinical states of prostate
cancer (PCa) progression. Gel electrophoretic analyses combined with western blot
showed that, in androgen-dependent PCa and CRPC in vitro models, the subcellular
distribution of spliced and serine-phosphorylated heterogeneous nuclear
ribonucleoprotein K (hnRNP K) isoforms can be associated with different AR
activities. Using mass spectrometry and bioinformatic analyses, we showed that
the protein sets of androgen-dependent (LNCaP) and ADT-resistant cell lines (PDB
and MDB) co-immunoprecipitated with hnRNP K varied depending on the cell type,
unravelling a dynamic relationship between hnRNP K and AR during PCa progression
to CRPC. By comparing the interactome of LNCaP, PDB, and MDB cell lines, we
identified 51 proteins differentially interacting with hnRNP K, among which KLK3,
SORD, SPON2, IMPDH2, ACTN4, ATP1B1, HSPB1, and KHDRBS1 were associated with AR
and differentially expressed in normal and tumor human prostate tissues. This
hnRNP K-AR-related signature, associated with androgen sensitivity and PCa
progression, may help clinicians to better manage patients with CRPC.
PMID- 29966327
TI - Application of the Fluorescent Dye BODIPY in the Study of Lipid Dynamics of the
Rice Blast Fungus Magnaporthe oryzae.
AB - Rice blast is one of the most serious diseases affecting rice yield which is
caused by Magnaporthe oryzae, a model organism for studies on plant pathogenic
fungi. Lipids stored in M. oryzae cells have been shown to be crucial for the
development of appressorium turgor and the ability of the pathogen to cause
infection. Nile red staining is a common method to study lipid dynamics in
phytopathogenic fungi. However, the disadvantages of this dye include its wide
spectrum, poor water solubility, and susceptibility to quenching. Boron
dipyrromethene (BODIPY) is a new type of fluorescent dye that has a different
emission wavelength to that of Nile red as well as many desirable spectral and
chemical properties. In this study, we used BODIPY to stain the lipids in M.
oryzae cells to seek a possible substitute to Nile red in the study of lipid
dynamics in plant pathogenic fungi. Our data showed that through simple and
routine procedures, BODIPY was able to distinctly label lipids in the cells of
mycelia and conidia. The positions of lipids labeled by BODIPY were essentially
identical to those labeled by Nile red, but with more clear fluorescence
labelling, lower background, and higher specificity. The use of BODIPY to stain
germinating M. oryzae conidia allowed the lipid dynamics to be clearly tracked
during this process. We also achieved double and multiple fluorescent staining
conidia by combining BODIPY with the red fluorescent protein mCherry and other
fluorescent dyes, such as Calcofluor white and DAPI, in conidia, mycelia, and
sexual structures of M. oryzae. These results indicate that BODIPY is an ideal
fluorescent dye for staining fungal lipids and provide a method for the study of
the lipid dynamics and lipid metabolism in plant pathogenic fungi.
PMID- 29966328
TI - Improving the Performance of an SPR Biosensor Using Long-Range Surface Plasmon of
Ga-Doped Zinc Oxide.
AB - Transparent conducting oxides (TCOs) have appeared in the past few years as
potential plasmonic materials for the development of optical devices in the near
infrared regime (NIR). However, the performance of biosensors with TCOs has been
limited in sensitivity and figure of merit (FOM). To improve the performance of
the biosensors with TCOs, a biosensor based on long-range surface plasmon with Ga
doped zinc oxide (GZO) is proposed. It is shown that a larger FOM with a 2~7
times enhancement compared to the traditional surface plasmon polaritons (SPPs)
sensor and higher detection accuracy (DA) can be realized in our proposed sensor
compared with the surface plasmon resonance (SPR) sensor with GZO. Therefore,
this sensor can be used to detect biological activity or chemical reactions in
the near infrared region.
PMID- 29966329
TI - Resistance Development to Bacteriophages Occurring during Bacteriophage Therapy.
AB - Bacteriophage (phage) therapy, i.e., the use of viruses that infect bacteria as
antimicrobial agents, is a promising alternative to conventional antibiotics.
Indeed, resistance to antibiotics has become a major public health problem after
decades of extensive usage. However, one of the main questions regarding phage
therapy is the possible rapid emergence of phage-resistant bacterial variants,
which could impede favourable treatment outcomes. Experimental data has shown
that phage-resistant variants occurred in up to 80% of studies targeting the
intestinal milieu and 50% of studies using sepsis models. Phage-resistant
variants have also been observed in human studies, as described in three out of
four clinical trials that recorded the emergence of phage resistance. On the
other hand, recent animal studies suggest that bacterial mutations that confer
phage-resistance may result in fitness costs in the resistant bacterium, which,
in turn, could benefit the host. Thus, phage resistance should not be
underestimated and efforts should be made to develop methodologies for monitoring
and preventing it. Moreover, understanding and taking advantage of the resistance
induced fitness costs in bacterial pathogens is a potentially promising avenue.
PMID- 29966330
TI - Exposure to Environmental Tobacco Smoke in Relation to Behavioral, Emotional,
Social and Health Indicators of Slovak School Children.
AB - Environmental tobacco smoke (ETS) exposure has been shown in general as a major
environmental risk factor and deserves attention in vulnerable population groups.
The aim of the project is to analyze the relationships among the ETS and behavior
and health in 6−15-year-old children in Slovakia. The status of physical
and mental health of children in relation to exposure to tobacco smoke was
examined in a representative group of 1478 school children. The methods used,
included anonymous questionnaires filled in by parents, Columbia Impairment Scale
(CIS), Behavior Problem Index (BPI) and anthropometry. The prevalence of ETS
exposure is the highest in the capital (27%) and southern cities. A significant
association was found between ETS and age, socio-economic status, incompleteness
of the family, level of mother’s education and a higher prevalence of
respiratory diseases (26.7%). The relationships of ETS with emotional (CIS scores
≥ 16) and behavioral functions (BPI score ≥ 14) were significant in
children exposed to mother’s or father’s smoking at home. In the
multivariate analysis these associations were not significant; the factors such
as income and completeness of the family were dominant. The results showed mostly
the predominant impact of social factors on the physical and mental health status
of Slovak school children.
PMID- 29966332
TI - Molybdenum-Catalyzed Enantioselective Sulfoxidation Controlled by a Nonclassical
Hydrogen Bond between Coordinated Chiral Imidazolium-Based Dicarboxylate and
Peroxido Ligands.
AB - Chiral alkyl aryl sulfoxides were obtained by molybdenum-catalyzed oxidation of
alkyl aryl sulfides with hydrogen peroxide as oxidant in mild conditions with
high yields and moderate enantioselectivities. The asymmetry is generated by the
use of imidazolium-based dicarboxylic compounds, HLR. The in-situ-generated
catalyst, a mixture of aqueous [Mo(O)(O2)2(H2O)n] with HLR as chirality
inductors, in the presence of [PPh4]Br, was identified as the anionic binuclear
complex [PPh4]{[Mo(O)(O2)2(H2O)]2(μ-LR)}, according to spectroscopic data and
Density Functional Theory (DFT) calculations. A nonclassical hydrogen bond
between one C-H bond of the alkyl R group of coordinated (LR)− and one
oxygen atom of the peroxido ligand was identified as the interaction responsible
for the asymmetry in the process. Additionally, the step that governs the
enantioselectivity was theoretically analyzed by locating the transition states
of the oxido-transfer to PhMeS of model complexes [Mo(O)(O2)2(H2O)(κ1-O
LR)]− (R = H, iPr). The ??G≠ is ca. 0 kcal?mol−1 for R = H,
racemic sulfoxide, meanwhile for chiral species the ??G≠ of ca. 2
kcal?mol−1 favors the formation of (R)-sulfoxide.
PMID- 29966331
TI - Dietary Leucine Supplement Ameliorates Hepatic Steatosis and Diabetic Nephropathy
in db/db Mice.
AB - Dietary leucine supplementation has been explored for the therapeutic
intervention of obesity and obesity-induced metabolic dysfunctions. In this
study, we aim to examine the effects of dietary leucine supplementation in db/db
mice. Mice were treated with or without leucine (1.5% w/v) in drinking water for
12 weeks. The leucine supplement was found to reduce insulin resistance and
hepatic steatosis in db/db mice. Using Nuclear Magnetic Resonance (NMR)-based
lipidomics, we found that the reduction of hepatic triglyceride synthesis was
correlated with attenuated development of fatty liver. In addition, diabetic
nephropathy (DN) was also ameliorated by leucine. Using liquid chromatography
time-of-flight mass spectrometry (LC-TOF MS)-based urine metabolomics analysis,
we found that the disturbance of the tricarboxylic acid (TCA) cycle was reversed
by leucine. The beneficial effects of leucine were probably due to AMP-activated
protein kinase (AMPK) activation in the liver and kidneys of db/db mice. Thus,
dietary leucine supplementation may potentially be a nutritional intervention to
attenuate hepatic steatosis and early DN in type II diabetes.
PMID- 29966333
TI - High-Temperature Molecular Beam Epitaxy of Hexagonal Boron Nitride with High
Active Nitrogen Fluxes.
AB - Hexagonal boron nitride (hBN) has attracted a great deal of attention as a key
component in van der Waals (vdW) heterostructures, and as a wide band gap
material for deep-ultraviolet devices. We have recently demonstrated plasma
assisted molecular beam epitaxy (PA-MBE) of hBN layers on substrates of highly
oriented pyrolytic graphite at high substrate temperatures of ~1400 °C. The
current paper will present data on the high-temperature PA-MBE growth of hBN
layers using a high-efficiency radio-frequency (RF) nitrogen plasma source.
Despite more than a three-fold increase in nitrogen flux with this new source, we
saw no significant increase in the growth rates of the hBN layers, indicating
that the growth rate of hBN layers is controlled by the boron arrival rate. The
hBN thickness increases to 90 nm with decrease in the growth temperature to 1080
°C. However, the decrease in the MBE temperature led to a deterioration in
the optical properties of the hBN. The optical absorption data indicates that an
increase in the active nitrogen flux during the PA-MBE process improves the
optical properties of hBN and suppresses defect related optical absorption in the
energy range 5.0-5.5 eV.
PMID- 29966334
TI - Physiological and Phylogenetic Characterization of Rhodotorula diobovata DSBCA06,
a Nitrophilous Yeast.
AB - Agriculture and intensive farming methods are the greatest cause of nitrogen
pollution. In particular, nitrification (the conversion of ammonia to nitrate)
plays a role in global climate changes, affecting the bio-availability of
nitrogen in soil and contributing to eutrophication. In this paper, the
Rhodotorula diobovata DSBCA06 was investigated for growth kinetics on nitrite,
nitrate, or ammonia as the sole nitrogen sources (10 mM). Complete nitrite
removal was observed in 48 h up to 10 mM initial nitrite. Nitrogen was almost
completely assimilated as organic matter (up to 90% using higher nitrite
concentrations). The strain tolerates and efficiently assimilates nitrite at
concentrations (up to 20 mM) higher than those previously reported in literature
for other yeasts. The best growth conditions (50 mM buffer potassium phosphate pH
7, 20 g/L glucose as the sole carbon source, and 10 mM nitrite) were determined.
In the perspective of applications in inorganic nitrogen removal, other metabolic
features relevant for process optimization were also evaluated, including
renewable sources and heavy metal tolerance. Molasses, corn, and soybean oils
were good substrates, and cadmium and lead were well tolerated. Scale-up tests
also revealed promising features for large-scale applications. Overall, presented
results suggest applicability of nitrogen assimilation by Rhodotorula diobovata
DSBCA06 as an innovative tool for bioremediation and treatment of wastewater
effluents.
PMID- 29966335
TI - Suicide Attempts in Michigan HealthCare System; Racial Differences.
AB - BACKGROUND: Community-based studies have documented racial differences in social,
psychiatric, and medical determinants of suicidal ideation; however, less is
known about racial differences in the profile of suicide attempts in clinical
settings. AIM: The current study aimed to compare Blacks and Whites who attempted
suicide for demographic factors, socioeconomic status, medical history,
psychiatric disorders, and outcomes. METHODS: This retrospective study was a
retrospective chart review of DataDirect, which is an electronic data repository
of the Michigan Health Care System, 2014 to 2017. This analysis included 6147
suicide attempts (5388 Whites and 759 Blacks). Race, sociodemographic factors,
medical history, psychiatric disorders, and outcomes were measured. RESULTS:
Blacks and Whites with suicide attempt did not differ in age or gender, but
varied by insurance type. Blacks were more commonly under Medicare and Medicaid,
while Whites were more commonly under private insurance or self-pay (p < 0.05).
Blacks with suicide attempt were more likely to be obese, while Whites with
suicide attempt were more likely to be underweight. Frequency of psychiatric
disorders, including depression, alcohol abuse, drug abuse, and psychosis, were
not different between Whites and Blacks with suicide attempt; however, medical
conditions showed a different profile across racial groups. When compared to
Whites, Blacks had higher prevalence of uncomplicated hypertension, renal
failure, chronic obstructive pulmonary disease, coagulopathy, and obesity (p <
0.05 for all comparisons). In contrast, Whites had higher prevalence of other
neurological disorders than Blacks. There were no differences in in-patient
survival rate between Whites and Blacks who attempted suicide. CONCLUSION: There
are considerable differences between Blacks and Whites with at least one suicide
attempt. Although their psychiatric diagnoses seem to be similar, Blacks who have
attempted suicide attempt have more medical comorbidities than their White
counterparts. Lack of racial disparities in in-patient mortality rate of suicide
attempts in the Michigan Health Care System is promising news given the higher
physical health needs of Blacks when compared to Whites.
PMID- 29966336
TI - Nucleolar GTP-Binding Protein 1-2 (NOG1-2) Interacts with Jasmonate-ZIMDomain
Protein 9 (JAZ9) to Regulate Stomatal Aperture during Plant Immunity.
AB - Plant defense responses at stomata and apoplast are the most important early
events during plant-bacteria interactions. The key components of stomatal defense
responses have not been fully characterized. A GTPase encoding gene, NOG1-2,
which is required for stomatal innate immunity against bacterial pathogens, was
recently identified. Functional studies in Arabidopsis revealed that NOG1-2
regulates guard cell signaling in response to biotic and abiotic stimulus through
jasmonic acid (JA)- and abscisic acid (ABA)-mediated pathways. Interestingly, in
this study, Jasmonate-ZIM-domain protein 9 (JAZ9) was identified to interact with
NOG1-2 for the regulation of stomatal closure. Upon interaction, JAZ9 reduces
GTPase activity of NOG1-2. We explored the role of NOG1-2 binding with JAZ9 for
COI1-mediated JA signaling and hypothesized that its function may be closely
linked to MYC2 transcription factor in the regulation of the JA-signaling cascade
in stomatal defense against bacterial pathogens. Our study provides valuable
information on the function of a small GTPase, NOG1-2, in guard cell signaling
and early plant defense in response to bacterial pathogens.
PMID- 29966337
TI - In Vitro Transcriptome Response to a Mixture of Lactobacilli Strains in
Intestinal Porcine Epithelial Cell Line.
AB - BACKGROUND: Food and feed supplements containing microorganisms with probiotic
potential are of increasing interest due to their healthy promoting effect on
human and animals. Their mechanism of action is still unknown. Using a microarray
approach, the aim of this study was to investigate the differences in genome-wide
gene expression induced by a mixture of three Lactobacillus strains (L.
rhamnosus, L. plantarum, and L. paracasei) in intestinal porcine epithelial cells
(IPEC-1) and to identify the genes and pathways involved in intestinal barrier
functions. METHODS: Undifferentiated IPEC-1 cells seeded at a density of 2.0
× 105/mL in 24-wells culture plates were cultivated at 37 °C and 5% CO2
until they reached confluence (2-3 days). Confluent cells monolayer were then
cultivated with 1 mL of fresh lactobacilli (LB) mixture suspension prepared for a
concentration of approximately 3.3 × 107 CFU/mL for each strain (1 ×
108 CFU/mL in total) for 3 h and analyzed by microarray using Gene Spring GX
v.11.5. RESULTS: The functional analysis showed that 1811 of the genes modulated
by LB treatment are involved in signaling (95% up-regulation, 121 genes with a
fold change higher than 10). The most enhanced expression was registered for
AXIN2 (axis inhibition protein 2-AXIN2) gene (13.93 Fc, p = 0.043), a negative
regulator of β-catenin with a key role in human cancer. LB affected the
cellular proliferation by increasing 10 times (Fc) the NF1 gene encoding for the
neurofibromin protein, a tumor suppressor that prevent cells from uncontrolled
proliferation. The induction of genes like serpin peptidase inhibitor, clade A
member 3 (SERPINA 3), interleukin-20 (IL-20), oncostatin M(OSM), granulocyte
macrophage colony-stimulating factor (GM-CSF), and the suppression of chemokine
(C-X-C motif) ligand 2/macrophage inflammatory protein 2-alpha (CXCL-2/MIP-2),
regulator of G-protein signaling 2 (RGS2), and of pro-inflammatory interleukin-18
(IL-18) genes highlights the protective role of lactobacilli in epithelial
barrier function against inflammation and in the activation of immune response.
CONCLUSION: Gene overexpression was the predominant effect produced by
lactobacilli treatment in IPEC-1 cells, genes related to signaling pathways being
the most affected. The protective role of lactobacilli in epithelial barrier
function against inflammation and in the activation of immune response was also
noticed.
PMID- 29966338
TI - Fabrication of Scaffold-Based 3D Magnetic Nanowires for Domain Wall Applications.
AB - Three-dimensional magnetic nanostructures hold great potential to revolutionize
information technologies and to enable the study of novel physical phenomena. In
this work, we describe a hybrid nanofabrication process combining bottom-up 3D
nano-printing and top-down thin film deposition, which leads to the fabrication
of complex magnetic nanostructures suitable for the study of new 3D magnetic
effects. First, a non-magnetic 3D scaffold is nano-printed using Focused Electron
Beam Induced Deposition; then a thin film magnetic material is thermally
evaporated onto the scaffold, leading to a functional 3D magnetic nanostructure.
Scaffold geometries are extended beyond recently developed single-segment
geometries by introducing a dual-pitch patterning strategy. Additionally, by
tilting the substrate during growth, low-angle segments can be patterned,
circumventing a major limitation of this nano-printing process; this is
demonstrated by the fabrication of ‘staircase’ nanostructures with
segments parallel to the substrate. The suitability of nano-printed scaffolds to
support thermally evaporated thin films is discussed, outlining the importance of
including supporting pillars to prevent deformation during the evaporation
process. Employing this set of methods, a set of nanostructures tailored to
precisely match a dark-field magneto-optical magnetometer have been fabricated
and characterized. This work demonstrates the versatility of this hybrid
technique and the interesting magnetic properties of the nanostructures produced,
opening a promising route for the development of new 3D devices for applications
and fundamental studies.
PMID- 29966339
TI - Multimed: An Integrated, Multi-Application Platform for the Real-Time Recording
and Sub-Millisecond Processing of Biosignals.
AB - Enhanced understanding and control of electrophysiology mechanisms are
increasingly being hailed as key knowledge in the fields of modern biology and
medicine. As more and more excitable cell mechanics are being investigated and
exploited, the need for flexible electrophysiology setups becomes apparent. With
that aim, we designed Multimed, which is a versatile hardware platform for the
real-time recording and processing of biosignals. Digital processing in Multimed
is an arrangement of generic processing units from a custom library. These can
freely be rearranged to match the needs of the application. Embedded onto a Field
Programmable Gate Array (FPGA), these modules utilize full-hardware signal
processing to lower processing latency. It achieves constant latency, and sub
millisecond processing and decision-making on 64 channels. The FPGA core
processing unit makes Multimed suitable as either a reconfigurable
electrophysiology system or a prototyping platform for VLSI implantable medical
devices. It is specifically designed for open- and closed-loop experiments and
provides consistent feedback rules, well within biological microseconds
timeframes. This paper presents the specifications and architecture of the
Multimed system, then details the biosignal processing algorithms and their
digital implementation. Finally, three applications utilizing Multimed in
neuroscience and diabetes research are described. They demonstrate the
system’s configurability, its multi-channel, real-time processing, and its
feedback control capabilities.
PMID- 29966340
TI - A Data Model for Using OpenStreetMap to Integrate Indoor and Outdoor Route
Planning.
AB - With a rapidly-growing volume of volunteered geographic information (VGI), there
is an increasing trend towards using VGI to provide location-based services. In
this study, we investigate using OpenStreetMap data to integrate indoor and
outdoor route planning for pedestrians. To support indoor and outdoor route
planning, in this paper, we focus on the connections inside buildings and propose
a data model, which uses OSM primitives (nodes, ways and relations) and tags to
capture horizontal and vertical indoor components, as well as the connection
between indoor and outdoor environments. A set of new approaches is developed to
support indoor modeling and mapping. Based on the proposed data model, we present
a workflow that enables automatic generation of a routing graph and provide an
algorithm to calculate integrated indoor-outdoor routes. We applied our data
model to a set of test cases. The application results demonstrate the capability
of our data model in modeling built environments and its feasibility for the
integration of indoor and outdoor navigation.
PMID- 29966341
TI - Who and Where: A Socio-Spatial Integrated Approach for Community-Based Health
Research.
AB - Social and spatial characteristics of a population often interact to influence
health outcomes, suggesting a need to jointly analyze both to offer useful
insights in community health. However, researchers have used either social or
spatial analyses to examine community-based health issues and inform intervention
programs. We propose a combined socio-spatial analytic approach to develop a
social network with spatial weights and a spatial statistic with social weights,
and apply them to an ongoing study of mental and physical well-being of rural
Latino immigrants in North Florida, USA. We demonstrate how this approach can be
used to calculate measures, such as social network centrality, support contact
dyads, and spatial kernel density based on a health survey data. Findings reveal
that the integrated approach accurately reflected interactions between social and
spatial elements, and identified community members (who) and locations (where)
that should be prioritized for community-based health interventions.
PMID- 29966342
TI - A Novel Method of Synthesizing Graphene for Electronic Device Applications.
AB - This article reports a novel and efficient method to synthesize graphene using a
thermal decomposition process. In this method, silicon carbide (SiC) thin films
grown on Si(100) wafers with an AlN buffer layer were used as substrates. CO2
laser beam heating, without vacuum or controlled atmosphere, was applied for SiC
thermal decomposition. The physical, chemical, morphological, and electrical
properties of the laser-produced graphene were investigated for different laser
energy densities. The results demonstrate that graphene was produced in the form
of small islands with quality, density, and properties depending on the applied
laser energy density. Furthermore, the produced graphene exhibited a sheet
resistance characteristic similar to graphene grown on mono-crystalline SiC
wafers, which indicates its potential for electronic device applications.
PMID- 29966344
TI - A Conformal Driving Class IV Flextensional Transducer.
AB - Class IV Flextensional Transducers (FTs) are the most popular among various FTs
used as low-frequency and high power underwater acoustic sources. However, an
undeniable fact exists in Class IV FTs is that the resonance frequency of
breathing mode regulator used is fairly raised by its longitudinal driver stacks.
In this research, a conformal driving Class IV FT in which the driver stacks are
kept conformal with its oval shell was proposed aiming at the limitations of
conventional driving Class IV FTs described above. The device exhibits
competitive Transmitting Voltage Responses (TVRs) but much lower operation
frequencies with respect to conventional driving Class IV FTs, through the
designs of conformal and segmentally controlled driver stacks. Geometric
parameters analysis was carried out extensively by Finite Element (FE)
simulations for the design optimizations and then a conformal driving Class IV FT
resonating at 510 Hz (45% approximately lower than that of conventional driving
Class IV FT with the same shell geometry) was finalized. Subsequently the
conformal driving Class IV was fabricated and tested in the anechoic tank
experimentally. Good agreements of both FE predictions and experimental results
demonstrate its low-frequency and small-size acoustic performance.
PMID- 29966343
TI - Smart Optical Catheters for Epidurals.
AB - Placing the needle inside the epidural space for locoregional anesthesia is a
challenging procedure, which even today is left to the expertise of the operator.
Recently, we have demonstrated that the use of optically sensorized needles
significantly improves the effectiveness of this procedure. Here, we propose an
optimized configuration, where the optical fiber strain sensor is directly
integrated inside the epidural catheter. The new design allows the solving of the
biocompatibility issues and increases the versatility of the former
configuration. Through an in vivo study carried out on a porcine model, we
confirm the reliability of our approach, which also opens the way to catheter
monitoring during insertion inside biological spaces.
PMID- 29966345
TI - Probing the Effect of Physiological Concentrations of IL-6 on Insulin Secretion
by INS-1 832/3 Insulinoma Cells under Diabetic-Like Conditions.
AB - Exercise improves insulin secretion by pancreatic beta cells (β-cells) in
patients with type 2 diabetes, but molecular mechanisms of this effect are yet to
be determined. Given that contracting skeletal muscle causes a spike in
circulating interleukin-6 (IL-6) levels during exercise, muscle-derived IL-6 is a
possible endocrine signal associated with skeletal muscle to β-cell
crosstalk. Evidence to support a role of IL-6 in regulating the health and
function of β-cells is currently inconsistent and studies investigating the
role of IL-6 on the function of β-cells exposed to type 2 diabetic-like
conditions are limited and often confounded by supraphysiological IL-6
concentrations. The purpose of this study is to explore the extent by which an
exercise-relevant concentration of IL-6 influences the function of pancreatic
β-cells exposed to type 2 diabetic-like conditions. Using insulin-secreting
INS-1 832/3 cells as an experimental β-cell model, we show that 1-h IL-6 (10
pg/mL) has no effect on insulin secretion under normal conditions and does not
restore the loss of insulin secretion caused by elevated glucose +/- palmitate or
IL-1β. Moreover, treatment of INS-1 832/3 cells to medium collected from
C2C12 myotubes conditioned with electrical pulse stimulation does not alter
insulin secretion despite significant increases in IL-6. Since insulin secretory
defects caused by diabetic-like conditions are neither improved nor worsened by
exposure to physiological IL-6 levels, we conclude that the beneficial effect of
exercise on β-cell function is unlikely to be driven by muscle-derived IL-6.
PMID- 29966346
TI - The Effect of Polymer Microstructure on Encapsulation Efficiency and Release
Kinetics of Citropin 1.1 from the Poly(epsilon-caprolactone) Microparticles.
AB - Cationic antimicrobial peptides represent a promising therapeutic option against
multidrug-resistant bacteria for the treatment of local infections. However, due
to their low stability and potential toxicity, there are limited possibilities
for their application in clinical practice. In this study, different
poly(ε-caprolactone) (PCL) microparticles (MPs) loaded with citropin 1.1
(CIT) were investigated in order to demonstrate the effect of the polymer
microstructure on the encapsulation efficiency (EE) and kinetics of the peptide
release from the newly developed devices. The characteristics of the new systems
in terms of surface morphology, particle size, EE and zeta potential analysis, as
well as the haemolytic activities of the peptide were investigated. The in vitro
release kinetics of CIT from the MPs was also investigated. CIT loading was
favoured by a high content of negative charged linear polymer chains in the PCL
structure. The presence of non-charged, amorphous macrocycle domains results in
faster degradation of the PCL matrix. Depending on the crystallinity of the PCL,
the peptide release exhibited a near-zero-order or near-first-order profile with
no “burst release”. The results indicated that CIT-loaded PCL MPs
could potentially be a promising drug delivery system (DDS) for the treatment of
local infections.
PMID- 29966347
TI - End-of-Life Care in High-Grade Glioma Patients. The Palliative and Supportive
Perspective.
AB - High-grade gliomas (HGGs) are the most frequently diagnosed primary brain tumors.
Even though it has been demonstrated that combined surgical therapy,
chemotherapy, and radiotherapy improve survival, HGGs still harbor a very poor
prognosis and limited overall survival. Differently from other types of primary
neoplasm, HGG manifests also as a neurological disease. According to this,
palliative care of HGG patients represents a peculiar challenge for healthcare
providers and caregivers since it has to be directed to both general and
neurological cancer symptoms. In this way, the end-of-life (EOL) phase of HGG
patients appears to be like a journey through medical issues, progressive
neurological deterioration, and psychological, social, and affective concerns.
EOL is intended as the time prior to death when symptoms increase and antitumoral
therapy is no longer effective. In this phase, palliative care is intended as an
integrated support aimed to reduce the symptoms burden and improve the Quality Of
Life (QOL). Palliative care is represented by medical, physical, psychological,
spiritual, and social interventions which are primarily aimed to sustain
patients’ functions during the disease time, while maintaining an
acceptable quality of life and ensuring a dignified death. Since HGGs represent
also a family concern, due to the profound emotional and relational issues that
the progression of the disease poses, palliative care may also relieve the
distress of the caregivers and increase the satisfaction of patients’
relatives. We present the results of a literature review addressed to enlighten
and classify the best medical, psychological, rehabilitative, and social
interventions that are addressed both to patients and to their caregivers, which
are currently adopted as palliative care during the EOL phase of HGG patients in
order to orientate the best medical practice in HGG management.
PMID- 29966348
TI - Spatio-Temporal Modeling of Zika and Dengue Infections within Colombia.
AB - The aim of this study is to estimate the parallel relative risk of Zika virus
disease (ZVD) and dengue using spatio-temporal interaction effects models for one
department and one city of Colombia during the 2015-2016 ZVD outbreak. We apply
the integrated nested Laplace approximation (INLA) for parameter estimation,
using the epidemiological week (EW) as a time measure. At the departmental level,
the best model showed that the dengue or ZVD risk in one municipality was highly
associated with risk in the same municipality during the preceding EWs, while at
the city level, the final model selected established that the high risk of dengue
or ZVD in one census sector was highly associated not only with its neighboring
census sectors in the same EW, but also with its neighboring sectors in the
preceding EW. The spatio-temporal models provided smoothed risk estimates,
credible risk intervals, and estimation of the probability of high risk of dengue
and ZVD by area and time period. We explore the intricacies of the modeling
process and interpretation of the results, advocating for the use of spatio
temporal models of the relative risk of dengue and ZVD in order to generate
highly valuable epidemiological information for public health decision making.
PMID- 29966349
TI - Catalpol Inhibits Ischemia-Induced Premyelinating Oligodendrocyte Damage through
Regulation of Intercellular Calcium Homeostasis via Na+/Ca2+ Exchanger 3.
AB - The heightened vulnerability of premyelinating oligodendrocytes (PreOLs) in
response to hypoxia-ischemia may contribute to perinatal white matter injury and
subsequent neurobehavioral dysfunction. Intracellular Ca2+ overload is considered
a crucial mechanism predisposing PreOLs to ischemic injury. We previously
reported that catalpol, an iridoid glycoside extracted from Rehmannia root,
inhibits intracellular Ca2+ overload of PreOLs in an in vitro ischemia model.
However, the exact underlying mechanisms remain elusive. In the present study, we
aimed to investigate the protective effects of catalpol on PreOLs and to explore
the underlying mechanisms involved in the modulation of intracellular Ca2+
homeostasis. Postnatal day 2 (P2) Sprague-Dawley (SD) rats subjected to bilateral
common carotid artery ligation followed by exposure to 8% oxygen for 10 min were
used as a rat model of neonatal hypoxia-ischemia. We found that catalpol
significantly improved behavioral functions and prevented PreOL loss and
myelination deficit after hypoxia-ischemia. Our in vitro studies also confirmed
the direct effects of catalpol on oxygen-glucose deprivation (OGD)-induced cell
death and arrested maturation of PreOLs. Moreover, we demonstrated that catalpol
significantly inhibited intracellular Ca2+ overload and promoted the expression
of Na+/Ca2+ exchanger 3 (NCX3). Finally, we found that catalpol significantly
reduced mitochondrial damage and subsequent extracellular signal-regulated kinase
1/2 (ERK1/2) and poly-ADP-ribose polymerase-1 (PARP-1) activation. Treatment with
NCX3-preferring inhibitor 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB
R7943) significantly reversed the protective effects of catalpol on PreOLs under
OGD. Overall, our data suggest that catalpol protects PreOLs from ischemic injury
through regulation of intercellular Ca2+ homeostasis via upregulation of NCX3
activity.
PMID- 29966350
TI - Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New
Hopes-3.
PMID- 29966352
TI - Changes in Couple Relationship Dynamics among Low-Income Parents in a
Relationship Education Program Are Associated with Decreases in Their Children's
Mental Health Symptoms.
AB - Witnessing intimate partner violence (IPV) among parents negatively impacts
millions of children in the United States each year. Low-income families are
disproportionately affected by IPV compared to middle- and high-income
individuals, and are beginning to be the focus of IPV secondary prevention
interventions, including relationship education programs. Despite these
developments, few studies have examined changes in psychosocial functioning among
children of parents participating in relationship education programs. The current
study examined the extent to which changes in specific couple dynamics among
individuals from low-income backgrounds participating in a couple relationship
education program, Within My Reach, were associated with changes in child mental
health symptoms. A second purpose of this paper is to examine whether changes in
parent-child relationship quality mediates the association between changes in
couple dynamics and changes in child mental health difficulties. Participants (n
= 347) were parents who participated in Within My Reach as part of programming
offered at a large community agency. Decreases in negative couple conflict
behaviors, including conflict engagement, withdrawal and compliance, over the
course of the program were linked to decreases in child mental health
difficulties. In addition, increases in parent-child relationship quality
partially mediated the associations between decreases in compliance, as well as
increase in overall couple relationship quality, and decreases in child symptoms.
Community-based couple relationship education programs for low-income families
can potentially have multiple positive impacts throughout the family system,
including for children.
PMID- 29966353
TI - An Antenna Proximity Sensor for Mobile Terminals Using Reflection Coefficient.
AB - This paper presents a new antenna proximity sensor for mobile terminals based on
the measured reflection coefficient using a bidirectional coupler which is
positioned between the main antenna and the front-end module. Using the coupled
forward and reverse long-term evolution signals by the bidirectional coupler, the
reflection coefficient looking into the antenna was calculated in the base-band
processor. The measured reflection coefficients showed clear differences for both
the types of objects, and the distances between the terminal and the objects. The
proposed antenna proximity sensor showed a recognition distance that was
approximately 5 mm longer than that of a conventional capacitive proximity
sensor.
PMID- 29966351
TI - Adipose-Derived Mesenchymal Stem Cells: Are They a Good Therapeutic Strategy for
Osteoarthritis?
AB - : Osteoarthritis (OA) is a major cause of disability in elderly population around
the world. More than one-third of people over 65 years old shows either clinical
or radiological evidence of OA. There is no effective treatment for this
degenerative disease, due to the limited capacity for spontaneous cartilage
regeneration. Regarding the use of regenerative therapies, it has been reported
that one option to restore degenerated cartilage are adipose-derived mesenchymal
stem cells (ASCs). The purpose of this review is to describe and compare the
efficacy of ASCs versus other therapies in OA. METHODS: Recent studies have shown
that ASCs exert paracrine effects protecting against degenerative changes in
chondrocytes. According to the above, we have carried out a review of the
literature using a combination of osteoarthritis, stem cells, and regenerative
therapies as keywords. RESULTS: Conventional pharmacological therapies for OA
treatment are considered before the surgical option, however, they do not stop
the progression of the disease. Moreover, total joint replacement is not
recommended for patients under 55 years, and high tibia osteotomy (HTO) is a
viable solution to address lower limb malalignment with concomitant OA, but some
complications have been described. In recent years, the use of mesenchymal stem
cells (MSCs) as a treatment strategy for OA is increasing considerably, thanks to
their capacity to improve symptoms together with joint functionality and,
therefore, the patients’ quality of life. CONCLUSIONS: ASC therapy has a
positive effect on patients with OA, although there is limited evidence and
little long-term follow-up.
PMID- 29966354
TI - Energy Consumption Model for Sensor Nodes Based on LoRa and LoRaWAN.
AB - Energy efficiency is the key requirement to maximize sensor node lifetime. Sensor
nodes are typically powered by a battery source that has finite lifetime. Most
Internet of Thing (IoT) applications require sensor nodes to operate reliably for
an extended period of time. To design an autonomous sensor node, it is important
to model its energy consumption for different tasks. Each task consumes a power
consumption amount for a period of time. To optimize the consumed energy of the
sensor node and have long communication range, Low Power Wide Area Network
technology is considered. This paper describes an energy consumption model based
on LoRa and LoRaWAN, which allows estimating the consumed power of each sensor
node element. The definition of the different node units is first introduced.
Then, a full energy model for communicating sensors is proposed. This model can
be used to compare different LoRaWAN modes to find the best sensor node design to
achieve its energy autonomy.
PMID- 29966355
TI - Graphene Oxide/ZnS:Mn Nanocomposite Functionalized with Folic Acid as a Nontoxic
and Effective Theranostic Platform for Breast Cancer Treatment.
AB - Nanoparticle-based cancer theranostic agents generally suffer of poor
dispersability in biological media, re-agglomeration over time, and toxicity
concerns. To address these challenges, we developed a nanocomposite consisting of
chemically-reduced graphene oxide combined with manganese-doped zinc sulfide
quantum dots and functionalized with folic acid (FA-rGO/ZnS:Mn). We studied the
dispersion stability, Doxorubicin (DOX) loading and release efficiency, target
specificity, internalization, and biocompatibility of FA-rGO/ZnS:Mn against
folate-rich breast cancer cells, and compared to its uncoated counterpart
(rGO/ZnS:Mn). The results indicate that DOX is adsorbed on the graphene surface
via π-π stacking and hydrophobic interaction, with enhanced loading (~35%)
and entrapment (~60%) efficiency that are associated to the chelation of DOX and
surface Zn2+ ions. DOX release is favored under acidic conditions reaching a
release of up to 95% after 70 h. Membrane integrity of the cells assessed by
Lactate dehydrogenase (LDH) release indicate that the surface passivation caused
by folic acid (FA) functionalization decreases the strong hydrophobic interaction
between the cell membrane wall and the edges/corners of graphene flakes.
Chemotherapeutic effect assays reveal that the cancer cell viability was reduced
up to ~50% at 3 µg/mL of DOX-FA-rGO/ZnS:Mn exposure, which is more
pronounced than those obtained for free DOX at the same doses. Moreover, DOX
rGO/ZnS:Mn did not show any signs of toxicity. An opposite trend was observed for
cells that do not overexpress the folate receptors, indicating that FA
functionalization endows rGO/ZnS:Mn with an effective ability to discriminate
positive folate receptor cancerous cells, enhancing its drug loading/release
efficiency as a compact drug delivery system (DDS). This study paves the way for
the potential use of functionalized rGO/ZnS:Mn nanocomposite as a platform for
targeted cancer treatment.
PMID- 29966357
TI - Analysis of the Secondary Phases Formed by Corrosion of U3Si2-Al Research Reactor
Fuel Elements in the Presence of Chloride Rich Brines.
AB - Corrosion experiments with non-irradiated U3Si2-Al research reactor fuel samples
were carried out in synthetic MgCl2-rich brine to identify and quantify the
secondary phases because depending on their composition and on their amount, such
compounds can act as a sink for the radionuclide release in final repositories.
Within the experimental period of 100 days at 90 °C and anoxic conditions the
U3Si2-Al fuel sample was completely disintegrated. The obtained solids were
subdivided into different grain size fractions and non-ambient X-ray diffraction
(XRD) was applied for their qualitative and quantitative phase analysis. The
secondary phases consist of lesukite (aluminum chloro hydrate) and layered double
hydroxides (LDH) with varying chemical compositions. Furthermore, iron, residues
of non-corroded nuclear fuel (U3Si2), iron oxy hydroxides and chlorides were also
observed. In addition to high amorphous contents (>45 wt %) hosting the uranium,
the quantitative phase analysis showed, that LDH compounds and lesukite were the
major crystalline phases. Scanning electron microscopy (SEM) and energy
dispersive -Xray spectroscopy (EDS) confirmed the results of the XRD analysis.
Elemental analysis revealed that U and Al were concentrated in the solids.
However, most of the iron, added as Fe(II) aqueous species, remained in solution.
PMID- 29966356
TI - HSV as A Platform for the Generation of Retargeted, Armed, and Reporter
Expressing Oncolytic Viruses.
AB - Previously, we engineered oncolytic herpes simplex viruses (o-HSVs) retargeted to
the HER2 (epidermal growth factor receptor 2) tumor cell specific receptor by the
insertion of a single chain antibody (scFv) to HER2 in gD, gH, or gB. Here, the
insertion of scFvs to three additional cancer targets—EGFR (epidermal
growth factor receptor), EGFRvIII, and PSMA (prostate specific membrane
antigen)—in gD Δ6-38 enabled the generation of specifically
retargeted o-HSVs. Viable recombinants resulted from the insertion of an scFv in
place of aa 6-38, but not in place of aa 61-218. Hence, only the gD N-terminus
accepted all tested scFv inserts. Additionally, the insertion of mIL12 in the US1
US2 intergenic region of the HER2- or EGFRvIII-retargeted o-HSVs, and the further
insertion of Gaussia Luciferase, gave rise to viable recombinants capable of
secreting the cytokine and the reporter. Lastly, we engineered two known
mutations in gB; they increased the ability of an HER2-retargeted recombinant to
spread among murine cells. Altogether, current data show that the o-HSV carrying
the aa 6-38 deletion in gD serves as a platform for the specific retargeting of o
HSV tropism to a number of human cancer targets, and the retargeted o-HSVs serve
as simultaneous vectors for two molecules.
PMID- 29966358
TI - Preventive Effects of Dairy Products on Dementia and the Underlying Mechanisms.
AB - Alongside the rapid population aging occurring worldwide, the prevention of age
related memory decline and dementia has become a high priority. Dairy products
have many physiological effects owing to their contents of lactic acid bacteria
and the fatty acids and peptides generated during their fermentation. In
particular, several recent studies have elucidated the effects of fermented dairy
products on cognitive function. Epidemiological and clinical evidence has
indicated that fermented dairy products have preventive effects against dementia,
including Alzheimer’s disease. Recent preclinical studies have identified
individual molecules generated during fermentation that are responsible for those
preventive effects. Oleamide and dehydroergosterol have been identified as the
agents responsible for reducing microglial inflammatory responses and
neurotoxicity. In this review, the protective effects of fermented dairy products
and their components on cognitive function, the mechanisms underlying those
effects, and the prospects for their future clinical development will be
discussed.
PMID- 29966359
TI - Joint Risk of Rainfall and Storm Surges during Typhoons in a Coastal City of
Haidian Island, China.
AB - Public health risks from urban floods are a global concern. A typhoon is a
devastating natural hazard that is often accompanied by heavy rainfall and high
storm surges and causes serious floods in coastal cities. Affected by the same
meteorological systems, typhoons, rainfall, and storm surges are three variables
with significant correlations. In the study, the joint risk of rainfall and storm
surges during typhoons was investigated based on principal component analysis,
copula-based probability analysis, urban flood inundation model, and flood risk
model methods. First, a typhoon was characterized by principal component
analysis, integrating the maximum sustained wind (MSW), center pressure, and
distance between the typhoon center and the study area. Following this, the
Gumbel copula was selected as the best-fit copula function for the joint
probability distribution of typhoons, rainfall, and storm surges. Finally, the
impact of typhoons on the joint risk of rainfall and storm surges was
investigated. The results indicate the following: (1) Typhoons can be well
quantified by the principal component analysis method. (2) Ignoring the
dependence between these flood drivers can inappropriately underestimate the
flood risk in coastal regions. (3) The co-occurrence probability of rainfall and
storm surges increases by at least 200% during typhoons. Therefore, coastal urban
flood management should pay more attention to the joint impact of rainfall and
storm surges on flood risk when a typhoon has occurred. (4) The expected annual
damage is 0.82 million dollars when there is no typhoon, and it rises to 3.27
million dollars when typhoons have occurred. This indicates that typhoons greatly
increase the flood risk in coastal zones. The obtained results may provide a
scientific basis for urban flood risk assessment and management in the study
area.
PMID- 29966361
TI - The Microbial Community of a Terrestrial Anoxic Inter-Tidal Zone: A Model for
Laboratory-Based Studies of Potentially Habitable Ancient Lacustrine Systems on
Mars.
AB - Evidence indicates that Gale crater on Mars harboured a fluvio-lacustrine
environment that was subjected to physio-chemical variations such as changes in
redox conditions and evaporation with salinity changes, over time. Microbial
communities from terrestrial environmental analogues sites are important for
studying such potential habitability environments on early Mars, especially in
laboratory-based simulation experiments. Traditionally, such studies have
predominantly focused on microorganisms from extreme terrestrial environments.
These are applicable to a range of Martian environments; however, they lack
relevance to the lacustrine systems. In this study, we characterise an anoxic
inter-tidal zone as a terrestrial analogue for the Gale crater lake system
according to its chemical and physical properties, and its microbiological
community. The sub-surface inter-tidal environment of the River Dee estuary,
United Kingdom (53°21′15.40″ N, 3°10′24.95″ W)
was selected and compared with available data from Early Hesperian-time Gale
crater, and temperature, redox, and pH were similar. Compared to subsurface
‘groundwater’-type fluids invoked for the Gale subsurface, salinity
was higher at the River Dee site, which are more comparable to increases in
salinity that likely occurred as the Gale crater lake evolved. Similarities in
clay abundance indicated similar access to, specifically, the bio-essential
elements Mg, Fe and K. The River Dee microbial community consisted of taxa that
were known to have members that could utilise chemolithoautotrophic and
chemoorganoheterotrophic metabolism and such a mixed metabolic capability would
potentially have been feasible on Mars. Microorganisms isolated from the site
were able to grow under environment conditions that, based on mineralogical data,
were similar to that of the Gale crater’s aqueous environment at
Yellowknife Bay. Thus, the results from this study suggest that the microbial
community from an anoxic inter-tidal zone is a plausible terrestrial analogue for
studying habitability of fluvio-lacustrine systems on early Mars, using
laboratory-based simulation experiments.
PMID- 29966362
TI - Smooth 3D Dubins Curves Based Mobile Data Gathering in Sparse Underwater Sensor
Networks.
AB - Sensory data collection is one of the most important concerns in underwater
sensor networks (USNs). Because full connectivity cannot be guaranteed, mobile
data gathering with autonomous underwater vehicles (AUVs) is widely used in
sparse three-dimensional (3D) USNs to solve energy-imbalance problems between
different sensor nodes. AUVs with relatively abundant energy and storage can
collect sensory data from one sensor node to transmit to another node, so as to
avoid energy-intensive multi-hop transmission. As a result, movement control
strategy and data collecting path planning for AUVs are very crucial for the
performance of data acquisition. This paper proposes a smooth 3D Dubins curves
based mobile data gathering mechanism to overcome the kinematic nonholonomic
constraints of AUVs. The objective of our proposed method is to collect sensory
data along smooth 3D Dubins paths, which are interpolated by continuous Bezier
curves in the Z-axis from 2D Dubins curves. Extensive simulation results verify
that the proposed method has a more efficient performance in terms of path
smoothness and energy consumption; thus it is very suitable for mobile data
collection in 3D underwater sensor networks.
PMID- 29966360
TI - Molecular Regulation of Differentiation in Early B-Lymphocyte Development.
AB - B-lymphocyte differentiation is one of the best understood developmental pathways
in the hematopoietic system. Our understanding of the developmental trajectories
linking the multipotent hematopoietic stem cell to the mature functional B
lymphocyte is extensive as a result of efforts to identify and prospectively
isolate progenitors at defined maturation stages. The identification of defined
progenitor compartments has been instrumental for the resolution of the molecular
features that defines given developmental stages as well as for our understanding
of the mechanisms that drive the progressive maturation process. Over the last
years it has become increasingly clear that the regulatory networks that control
normal B-cell differentiation are targeted by mutations in human B-lineage
malignancies. This generates a most interesting link between development and
disease that can be explored to improve diagnosis and treatment protocols in
lymphoid malignancies. The aim of this review is to provide an overview of our
current understanding of molecular regulation in normal and malignant B-cell
development.
PMID- 29966363
TI - Neuroprotective Effects of Soy Isoflavones on Scopolamine-Induced Amnesia in
Mice.
AB - In the recent years, interest in soybean as a neuroprotective nutrient in the
management of Alzheimer’s disease (AD) has increased and soy isoflavones
(SI), as kinds of soybean phytochemicals, are thought to be biologically active
components that confer this beneficial effect against neurodegenerative diseases.
However, the neuroprotective effect of SI is not well understood. Therefore, the
present study (30 days) was conducted to investigate the neuroprotective effects
of soy isoflavones (SI) on scopolamine (SCOP)-induced memory impairments in
Institute of Cancer Research (ICR) mice (aged 4 weeks) and to elucidate its
underlying mechanisms of action. SI (40 mg/kg) administration improved the
cognitive performance of SCOP-treated mice in an object location recognition task
and the Morris water maze test. SI (40 mg/kg) administration significantly
enhanced cholinergic system function and suppressed oxidative stress levels in
the hippocampus of SCOP-treated mice. Furthermore, SI (40 mg/kg) treatment
markedly upregulated the phosphorylation levels of extracellular signal-regulated
kinase (ERK), cAMP response element-binding protein (CREB) and brain-derived
neurotrophic factor (BDNF) expression levels in the hippocampus. Taken together,
these results demonstrated that soy isoflavones exerted a significant
neuroprotective effect on cognitive dysfunctions induced by scopolamine,
suggesting that soy isoflavones could be a good candidate for possible treatment
of neurodegenerative diseases, such as Alzheimer’s disease (AD).
PMID- 29966364
TI - Pipeline Damage Detection Using Piezoceramic Transducers: Numerical Analyses with
Experimental Validation.
AB - This paper aims to set up a finite element model using piezoelectric elements to
realize pipeline structure damage identification analysis. Ultrasonic guided wave
propagation characteristics and damage identification of pipeline structures are
analyzed by the ABAQUS software. The pulse-echo method using an L(0, 2) mode
impulse guided wave with a central frequency of 70 kHz is applied to evaluate
different size circumferential cracks. An experiment was performed for the
validation of the numerical analysis results. Both of the results show that the
proposed FEM model with piezoelectric elements can efficiently reveal the dynamic
behaviors, which can be used in much more precise numerical simulations than the
equivalent dynamic displacement loading method.
PMID- 29966365
TI - NR1 and NR3B Composed Intranuclear N-methyl-d-aspartate Receptor Complexes in
Human Melanoma Cells.
AB - Heterotetrameric N-methyl-d-aspartate type glutamate receptors (NMDAR) are
cationic channels primarily permeable for Ca2+. NR1 and NR3 subunits bind
glycine, while NR2 subunits bind glutamate for full activation. As NR1 may
contain a nuclear localization signal (NLS) that is recognized by importin
α, our aim was to investigate if NMDARs are expressed in the nuclei of
melanocytes and melanoma cells. A detailed NMDAR subunit expression pattern was
examined by RT-PCRs (reverse transcription followed by polymerase chain
reaction), fractionated western blots and immunocytochemistry in human epidermal
melanocytes and in human melanoma cell lines A2058, HT199, HT168M1, MEL35/0 and
WM35. All kind of NMDAR subunits are expressed as mRNAs in melanocytes, as well
as in melanoma cells, while NR2B protein remained undetectable in any cell type.
Western blots proved the exclusive presence of NR1 and NR3B in nuclear fractions
and immunocytochemistry confirmed NR1-NR3B colocalization inside the nuclei of
all melanoma cells. The same phenomenon was not observed in melanocytes.
Moreover, protein database analysis revealed a putative NLS in NR3B subunit. Our
results support that unusual, NR1-NR3B composed NMDAR complexes are present in
the nuclei of melanoma cells. This may indicate a new malignancy-related
histopathological feature of melanoma cells and raises the possibility of a
glycine-driven, NMDA-related nuclear Ca2+-signalling in these cells.
PMID- 29966366
TI - Access Control Model Based on Time Synchronization Trust in Wireless Sensor
Networks.
AB - Internal reliability and external safety of Wireless Sensor Networks (WSN) data
transmission have become increasingly outstanding issues with the wide
applications of WSN. This paper proposes a new method for access control and
mitigation of interfering noise in time synchronization environments. First, a
formal definition is given regarding the impact interference noise has on the
clock skew and clock offset of each node. The degree of node interference
behavior is estimated dynamically from the perspective of time-stamp changes
caused by the interference noise. Secondly, a general access control model is
proposed to resist invasion of noise interference. A prediction model is
constructed using the Bayesian method for calculating the reliability of neighbor
node behavior in the proposed model. Interference noise, which attacks the time
synchronization, is regarded as the key factor for probability estimation of the
reliability. The result of the calculations determines whether it is necessary to
initiate synchronization filtering. Finally, a division of trust levels with
bilinear definition is employed to lower interference noise and improve the
quality of interference detection. Experimental results show that this model has
advantages in system overhead, energy consumption and testing errors, compared to
its counterparts. When the disturbance intensity of a WSN increases, the proposed
optimized algorithm converges faster with a lower network communication load.
PMID- 29966367
TI - A Novel Eddy Current Testing Error Compensation Technique Based on Mamdani-Type
Fuzzy Coupled Differential and Absolute Probes.
AB - Eddy current testing (ECT) is an accurate, widely used and well-understood
inspection technique, particularly in the aircraft and nuclear industries. The
coating thickness or lift-off will influence the measurement of defect depth on
pipes or plates. It will be an uncertain decision condition whether the defects
on a workpiece are cracks or scratches. This problem can lead to the occurrence
of pipe leakages, besides causing the degradation of a company’s
productivity and most importantly risking the safety of workers. In this paper, a
novel eddy current testing error compensation technique based on Mamdani-type
fuzzy coupled differential and absolute probes was proposed. The general
descriptions of the proposed ECT technique include details of the system design,
intelligent fuzzy logic design and Simulink block development design. The
detailed description of the proposed probe selection, design and instrumentation
of the error compensation of eddy current testing (ECECT) along with the absolute
probe and differential probe relevant to the present research work are presented.
The ECECT simulation and hardware design are proposed, using the fuzzy logic
technique for the development of the new methodology. The depths of the defect
coefficients of the probe’s lift-off caused by the coating thickness were
measured by using a designed setup. In this result, the ECECT gives an optimum
correction for the lift-off, in which the reduction of error is only within 0.1%
of its all-out value. Finally, the ECECT is used to measure lift-off in a range
of approximately 1 mm to 5 mm, and the performance of the proposed method in non
linear cracks is assessed.
PMID- 29966368
TI - Continued Susceptibility of the wMel Wolbachia Infection in Aedes aegypti to Heat
Stress Following Field Deployment and Selection.
AB - Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia are being
deployed to control the spread of arboviruses around the world through blockage
of viral transmission. Blockage by Wolbachia in some scenarios may be affected by
the susceptibility of wMel to cyclical heat stress during mosquito larval
development. We therefore evaluated the potential to generate a heat-resistant
strain of wMel in Ae. aegypti through artificial laboratory selection and through
exposure to field temperatures across multiple generations. To generate an
artificially selected strain, wMel-infected females reared under cyclical heat
stress were crossed to wMel-infected males reared at 26 °C. The low
proportion of larvae that hatched founded the next generation, and this process
was repeated for eight generations. The wMel heat-selected strain (wMel-HS) was
similar to wMel (unselected) in its ability to induce cytoplasmic incompatibility
and restore compatibility when larvae were reared under cyclical heat stress, but
wMel-HS adults exhibited reduced Wolbachia densities at 26 °C. To investigate
the effects of field exposure, we compared the response of wMel-infected Ae.
aegypti collected from Cairns, Australia where the infection has been established
for seven years, to a wMel-infected population maintained in the laboratory for
approximately 60 generations. Field and laboratory strains of wMel did not differ
in their response to cyclical heat stress or in their phenotypic effects at 26
°C. The capacity for the wMel infection in Ae. aegypti to adapt to high
temperatures therefore appears limited, and alternative strains may need to be
considered for deployment in environments where high temperatures are regularly
experienced in mosquito breeding sites.
PMID- 29966371
TI - Real Time Precise Relative Positioning with Moving Multiple Reference Receivers.
AB - The stationary reference receiver with precisely known coordinates is difficult
to establish in some special real-time relative positioning applications. To
improve the relative position estimation accuracy and the reliability
simultaneously for the RTK without a precisely known reference receiver, multiple
receivers mounted on a moving platform are used as the base station. A code and
phase measurement fusion model is proposed to reduce the communication burden and
generate measurements at any virtual position where it is inconvenient to install
the GPS receiver. To keep the integer property of the ambiguity of fused phase
measurements, the RTK method with the moving reference receivers is proposed by
implementing the integer ambiguity transformation and error absorption strategy
based on the known geometry of multiple receivers. Static and kinematic
experiments were carried out to evaluate the performance of the proposed relative
positioning method. When compared with the single-receiver solution, static
results have shown that the proposed method can improve position accuracy by
15.9% and 15.7% for the horizontal and the vertical component, respectively. The
kinematic results have shown that the proposed method can achieve position
accuracy enhancement by 26.9% for the vertical component.
PMID- 29966369
TI - Recent Progress in Gene Therapy for Ovarian Cancer.
AB - Ovarian cancer is the most lethal gynecological malignancy in developed
countries. This is due to the lack of specific symptoms that hinder early
diagnosis and to the high relapse rate after treatment with radical surgery and
chemotherapy. Hence, novel therapeutic modalities to improve clinical outcomes in
ovarian malignancy are needed. Progress in gene therapy has allowed the
development of several strategies against ovarian cancer. Most are focused on the
design of improved vectors to enhance gene delivery on the one hand, and, on the
other hand, on the development of new therapeutic tools based on the restoration
or destruction of a deregulated gene, the use of suicide genes, genetic
immunopotentiation, the inhibition of tumour angiogenesis, the alteration of
pharmacological resistance, and oncolytic virotherapy. In the present manuscript,
we review the recent advances made in gene therapy for ovarian cancer,
highlighting the latest clinical trials experience, the current challenges and
future perspectives.
PMID- 29966370
TI - The Genomics and Molecular Biology of Natural Killer/T-Cell Lymphoma:
Opportunities for Translation.
AB - Extranodal NK/T-cell lymphoma, nasal type (ENKTL), is an aggressive malignancy
with a poor prognosis. While the introduction of L-asparaginase in the treatment
of this disease has significantly improved the prognosis, the outcome of patients
relapsing after asparaginase-based chemotherapy, which occurs in up to 50% of
patients with disseminated disease, remains dismal. There is hence an urgent need
for effective targeted therapy especially in the relapsed/refractory setting.
Gene expression profiling studies have provided new perspectives on the molecular
biology, ontogeny and classification of ENKTL and further identified dysregulated
signaling pathways such as Janus associated kinase (/Signal Transducer and
activation of transcription (JAK/STAT), Platelet derived growth factor (PDGF),
Aurora Kinase and NF-κB, which are under evaluation as therapeutic targets.
Copy number analyses have highlighted potential tumor suppressor genes such as PR
Domain Zinc Finger Protein 1 (PRDM1) and protein tyrosine phosphatase kappa
(PTPRK) while next generation sequencing studies have identified recurrently
mutated genes in pro-survival and anti-apoptotic pathways. The discovery of
epigenetic dysregulation and aberrant microRNA activity has broadened our
understanding of the biology of ENKTL. Importantly, immunotherapy via Programmed
Cell Death -1 (PD-1) and Programmed Cell Death Ligand1 (PD-L1) checkpoint
signaling inhibition is emerging as an attractive therapeutic strategy in ENKTL.
Herein, we present an overview of the molecular biology and genomic landscape of
ENKTL with a focus on the most promising translational opportunities.
PMID- 29966373
TI - Impact of Strain and Morphology on Magnetic Properties of Fe3O4/NiO Bilayers
Grown on Nb:SrTiO3(001) and MgO(001).
AB - We present a comparative study of the morphology and structural as well as
magnetic properties of crystalline Fe3O4/NiO bilayers grown on both MgO(001) and
SrTiO3(001) substrates by reactive molecular beam epitaxy. These structures were
investigated by means of X-ray photoelectron spectroscopy, low-energy electron
diffraction, X-ray reflectivity and diffraction, as well as vibrating sample
magnetometry. While the lattice mismatch of NiO grown on MgO(001) was only 0.8%,
it was exposed to a lateral lattice mismatch of −6.9% if grown on SrTiO3.
In the case of Fe3O4, the misfit strain on MgO(001) and SrTiO3(001) amounted to
0.3% and −7.5%, respectively. To clarify the relaxation process of the
bilayer system, the film thicknesses of the magnetite and nickel oxide films were
varied between 5 and 20 nm. While NiO films were well ordered on both substrates,
Fe3O4 films grown on NiO/SrTiO3 exhibited a higher surface roughness as well as
lower structural ordering compared to films grown on NiO/MgO. Further, NiO films
grew pseudomorphic in the investigated thickness range on MgO substrates without
any indication of relaxation, whereas on SrTiO3 the NiO films showed strong
strain relaxation. Fe3O4 films also exhibited strong relaxation, even for films
of 5 nm thickness on both NiO/MgO and NiO/SrTiO3. The magnetite layers on both
substrates showed a fourfold magnetic in-plane anisotropy with magnetic easy axes
pointing in 100 directions. The coercive field was strongly enhanced for
magnetite grown on NiO/SrTiO3 due to the higher density of structural defects,
compared to magnetite grown on NiO/MgO.
PMID- 29966374
TI - LiReD: A Light-Weight Real-Time Fault Detection System for Edge Computing Using
LSTM Recurrent Neural Networks.
AB - Monitoring the status of the facilities and detecting any faults are considered
an important technology in a smart factory. Although the faults of machine can be
analyzed in real time using collected data, it requires a large amount of
computing resources to handle the massive data. A cloud server can be used to
analyze the collected data, but it is more efficient to adopt the edge computing
concept that employs edge devices located close to the facilities. Edge devices
can improve data processing and analysis speed and reduce network costs. In this
paper, an edge device capable of collecting, processing, storing and analyzing
data is constructed by using a single-board computer and a sensor. And, a fault
detection model for machine is developed based on the long short-term memory
(LSTM) recurrent neural networks. The proposed system called LiReD was
implemented for an industrial robot manipulator and the LSTM-based fault
detection model showed the best performance among six fault detection models.
PMID- 29966372
TI - How Healthy Lifestyle Factors at Midlife Relate to Healthy Aging.
AB - With increasing life expectancies worldwide, it is an important public health
issue to identify factors that influence the quality of aging. We aimed to
investigate the individual and combined roles of lifestyle factors at midlife for
healthy aging (HA). We analyzed data from 2203 participants of the French
”Supplémentation en Vitamines et Minéraux Antioxydants”
(SU.VI.MAX) cohort aged 45-60 years at baseline (1994-1995), and assessed the
combined impact of lifestyle factors (weight, smoking status, physical activity,
alcohol consumption, and diet) on HA (absence of chronic diseases and function
limiting pain, good physical and cognitive functioning, functional independence,
no depressive symptoms, and good social and self-perceived health) with a five
component healthy lifestyle index (HLI). Relative risks (RR) and 95% confidence
intervals (CIs) were estimated using a robust-error-variance Poisson regression.
Approximately 39% of our sample aged healthily. After adjustment for potential
confounders, a one-point increase in HLI was related to an 11% higher probability
of HA (95% CI = 6%, 16%; p < 0.001). The proportions of HA attributable to
specific factors based on the “population attributable risk” concept
were 7.6%, 6.0%, 7.8%, and 16.5% for body mass index (BMI), physical activity,
diet quality, and smoking status, respectively. This study highlights the
importance of healthy lifestyle habits at midlife for the promotion of good
overall health during aging.
PMID- 29966375
TI - Experiments on MEMS Integration in 0.25 MUm CMOS Process.
AB - In this paper, we share our practical experience gained during the development of
CMOS-MEMS (Complementary Metal-Oxide Semiconductor Micro Electro Mechanical
Systems) devices in IHP SG25 technology. The experimental prototyping process is
illustrated with examples of three CMOS-MEMS chips and starts from rough process
exploration and characterization, followed by the definition of the useful MEMS
design space to finally reach CMOS-MEMS devices with inertial mass up to 4.3
μg and resonance frequency down to 4.35 kHz. Furthermore, the presented design
techniques help to avoid several structural and reliability issues such as layer
delamination, device stiction, passivation fracture or device cracking due to
stress.
PMID- 29966376
TI - Phenotype and Viability of MLO-Y4 Cells Is Maintained by TGFbeta3 in a Serum
Dependent Manner within a 3D-Co-Culture with MG-63 Cells.
AB - The osteocyte network inside the bone matrix is of functional importance and
osteocyte cell death is a characteristic feature of pathological bone diseases.
Osteocytes have emerged as key regulators of bone tissue maintenance, yet
maintaining their phenotype during in vitro culture remains challenging. A 3D co
culture system for osteocytes with osteoblasts was recently presented, enabling
the determination of more physiological effects of growth factors on cells in
vitro. MLO-Y4 cells were embedded within a type I collagen gel and cultured in
the presence of surface MG-63 cells. Co-culture was performed in the presence or
absence of TGFβ3. Gene expression by quantitative PCR, protein expression by
fluorescent immunohistochemistry and cell viability tests were performed. The 3D
co-culture induced cell differentiation of MG-63 cells seen by increased type I
collagen and osteocalcin mRNA expression. TGFβ3 maintained osteocyte
differentiation of MLO-Y4 cells during co-culture as determined by stable E11 and
osteocalcin mRNA expression till day 4. Interestingly, most of the effects of
TGFβ3 on co-cultured cells were serum-dependent. Also, TGFβ3 reduced
cell death of 3D co-cultured MLO-Y4 cells in a serum-dependent manner. This study
shows that 3D co-culture upregulates differentiation of MG-63 cells to a more
mature osteoblast-like phenotype; while the addition of TGFβ3 maintained the
characteristic MLO-Y4 osteocyte-like phenotype and viability in a serum-dependent
manner.
PMID- 29966377
TI - High Body Mass Index Is Associated with the Extent of Muscle Damage after
Eccentric Exercise.
AB - Purpose: The present study aimed to investigate the effects of body mass index
(BMI), which is an obesity index, on the change in the muscle damage index after
eccentric exercise. Methods: Forty healthy male university students participated
in this study and were classified into normal (BMI 18.5-22.9 kg/m2, n = 20) and
high BMI groups (BMI ≥ 25 kg/m2, n = 20). For eccentric exercise, a modified
preacher curl machine was used. Participants performed two exercise sets with 25
repetitions in each set. With regard to the muscle damage index, maximum
strength, muscle soreness, and the creatine kinase (CK) level were measured.
Results: Loss of maximum strength, muscle soreness, and the CK level were higher
in the high BMI group than in the normal BMI group (p < 0.05, p < 0.05, and p <
0.01, respectively). Conclusions: In conclusion, BMI is one of the potential
factors related to muscle damage after eccentric exercise.
PMID- 29966378
TI - Broadband Perfect Absorber Based on TiN-Nanocone Metasurface.
AB - Based on an integrated array of refractory titanium nitride (TiN), a metasurface
perfect absorber (MPA) in the visible-to-near infrared (NIR) band is reported.
The systematic and detailed simulation study of the absorption of the MPA is
performed with the finite-different time-domain (FDTD) method. Tailoring the
structure, the MPA realizes as high an average as 99.6% broadband absorption,
ranging from 400 nm to 1500 nm. The broadband perfect absorption can be
attributed to localized surface plasmonic resonance (LSPR), excited by the
continuous diameter evolution from the apex to the base of the nanocone, and the
gap plasmons excited among the nanocones, as well as in the spacer layer at
longer wavelengths. Particularly, the coupling of the resonances is essentially
behind the broadening of the absorption spectrum. We also evaluated the electric
field intensity and polarization-dependence of the nanocone MPA to offer further
physical insight into light trapping capability. The MPA shows about 90% average
absorption even at an oblique incidence up to 50°, which improves the
acceptance capability of light-harvesting system applications. This unique design
with the TiN nanocone array/aluminium oxide (Al2O3)/TiN structure shows potential
in imminent applications in light trapping and thermophotovoltaics.
PMID- 29966379
TI - Climate Change Impacts on Disaster and Emergency Medicine Focusing on Mitigation
Disruptive Effects: an International Perspective.
AB - In recent decades, climate change has been responsible for an increase in the
average temperature of the troposphere and of the oceans, with consequences on
the frequency and intensity of many extreme weather phenomena. Climate
change’s effects on natural disasters can be expected to induce a rise in
humanitarian crises. In addition, it will surely impact the population’s
long-term general health, especially among the most fragile. There are
foreseeable health risks that both ambulatory care organizations and hospitals
will face as global temperatures rise. These risks include the geographic
redistribution of infectious (particularly zoonotic) diseases, an increase in
cardiac and respiratory illnesses, as well as a host of other health hazards.
Some of these risks have been detailed for most developed countries as well as
for some developing countries. Using these existing risk assessments as a
template, organizational innovations as well as implementation strategies should
be proposed to mitigate the disruptive effects of these health risks on emergency
departments and by extension, reduce the negative impact of climate change on the
populations they serve.
PMID- 29966380
TI - Evaluation of the PEG Density in the PEGylated Chitosan Nanoparticles as a Drug
Carrier for Curcumin and Mitoxantrone.
AB - Polyethylene glycolated (PEGylated)curcumin-grafted-chitosan (PCC) conjugates
were synthesized with three PEG/chitosan feed molar ratios (1/5, 1/7.5, and
1/10), namely PCC1, PCC2 and PCC3. Chemical structures of these conjugates were
characterized by Fourier transform infrared (FTIR) and proton nuclear magnetic
resonance (1H NMR). The degrees of substitution (DS) of PEG were 0.75%, 0.45% and
0.33%, respectively, for PCC1, PCC2 and PCC3by 1H NMR analysis. Self-assembled
PCC nanoparticles (NPs) were spherical as observed in transmission electron
microscope images. Mitoxantrone (MTO)-loaded PCC NPs were prepared to analyze the
particle size, zeta potential, drug loading, drug release and in vitro
cytotoxicity. The MTO-loaded PCC3 NP (DS = 0.33%) possessed the smallest size
(~183.1 nm), highest zeta potential (~+34.0 mV) and the largest loading capacity
of curcumin (CUR, ~16.1%) and MTO (~8.30%). The release results showed that MTO
loaded PCC3 NP demonstrated the lowest percentage of MTO release and increased as
pH decreased, but the CUR release could only be detected at pH 4.0. In the
cytotoxicity study, MTO-loaded PCC3 NP displayed the highest cytotoxicity in
HepG2 cell line and the best synergistic effect among the tested NPs. Our results
suggest that the DS of PEG has impacts on the structures and functions of PCC
NPs: the smaller DS of PEG was associated with the smaller size, the higher zeta
potential, the slower drug release, and the higher cytotoxicity of NPs.
PMID- 29966382
TI - Influenza Vaccination in Type 2 Diabetes Patients: Coverage Status and Its
Determinants in Southwestern Saudi Arabia.
AB - Despite the significant role of seasonal influenza vaccination in preventing and
minimizing the serious complications of influenza infection in type 2 diabetes
mellitus (T2DM) patients, unsatisfactory compliance still exists for vaccination.
Study objectives were to explore the vaccination status and determinants in T2DM
patients in southwestern Saudi Arabia. A cross-sectional study on a
representative sample of T2DM patients in Abha city, southwestern Saudi Arabia,
was conducted. Data for sociodemographic characteristics, clinical criteria,
vaccination status, vaccination motivators and barriers and seasonal influenza
knowledge were collected. Out of 353 T2DM patients included in the study,
seasonal influenza vaccination coverage was 61% in year 2017. A significant
factors associated with non-vaccination were; poor influenza and its vaccine
knowledge (OR = 4.31, 95% CI: 2.73-6.80), illiteracy (OR = 1.93, 95% CI: 1.11
3.37), and more than 10 years disease duration (OR = 2.07, 95% CI: 1.11-3.87).
Presence of family history of DM and ischemic heart comorbidity minimized the
possibility of non-vaccination (OR = 0.54 and 0.28 respectively). Healthcare
givers’ advice was the most reported vaccination motivator (84.7%) while;
fear of vaccine side effects was the most stated barrier (73%). In conclusion,
influenza vaccination rate among T2DM in the present study is less than the
recommended level. Continuous primary health care center-based educational
programs should be implemented to aware and encourage influenza vaccination among
T2DM patients.
PMID- 29966381
TI - In Vitro and In Vivo Experimental Studies of PM2.5 on Disease Progression.
AB - Air pollution is a very critical issue worldwide, particularly in developing
countries. Particulate matter (PM) is a type of air pollution that comprises a
heterogeneous mixture of different particle sizes and chemical compositions.
There are various sources of fine PM (PM2.5), and the components may also have
different effects on people. The pathogenesis of PM2.5 in several diseases
remains to be clarified. There is a long history of epidemiological research on
PM2.5 in several diseases. Numerous studies show that PM2.5 can induce a variety
of chronic diseases, such as respiratory system damage, cardiovascular
dysfunction, and diabetes mellitus. However, the epidemiological evidence
associated with potential mechanisms in the progression of diseases need to be
proved precisely through in vitro and in vivo investigations. Suggested
mechanisms of PM2.5 that lead to adverse effects and chronic diseases include
increasing oxidative stress, inflammatory responses, and genotoxicity. The aim of
this review is to provide a brief overview of in vitro and in vivo experimental
studies of PM2.5 in the progression of various diseases from the last decade. The
summarized research results could provide clear information about the mechanisms
and progression of PM2.5-induced disease.
PMID- 29966383
TI - Use of References in Responses from Scandinavian Drug Information Centres.
AB - Background: The aim of this study was to compare use of references in responses
from Scandinavian drug information centres (DICs). Methods: Six different
fictitious drug-related queries were sent to each of seven Scandinavian DICs. The
six queries concerned adverse effects, pharmacokinetics, pregnancy, complementary
medicine, polypharmacy, and breast feeding. References in the responses were
categorised into five types of drug information sources: primary (original
studies), secondary (reviews), tertiary (drug monographs, handbooks, etc.), DIC
database, or personal communication. Results: Two hundred and forty-four
references were used in the 42 responses. The mean number of references varied
from 3.0 to 10.6 for the six queries. The largest difference between centres with
regard to number of references used (range 1-17) was found for the query on
complementary medicine. In total, 124 references (50.8%) were tertiary, and only
10 of the 42 responses (23.8%) did not have any tertiary references included.
Complementary medicine, breast feeding, and pregnancy were query types associated
with relatively frequent use of primary references. Use of DIC database was not
uncommon, but personal communications were seldom used. Conclusions: Scandinavian
DICs differ substantially in number and type of references to identical drug
related queries. Tertiary sources are mainly preferred irrespective of type of
query.
PMID- 29966384
TI - p19-Targeting ILP Protein Blockers of IL-23/Th-17 Pro-Inflammatory Axis Displayed
on Engineered Bacteria of Food Origin.
AB - IL-23-mediated Th-17 cell activation and stimulation of IL-17-driven pro
inflammatory axis has been associated with autoimmunity disorders such as
Inflammatory Bowel Disease (IBD) or Crohn’s Disease (CD). Recently we
developed a unique class of IL-23-specific protein blockers, called ILP binding
proteins that inhibit binding of IL-23 to its cognate cell-surface receptor (IL
23R) and exhibit immunosuppressive effect on human primary blood leukocytes ex
vivo. In this study, we aimed to generate a recombinant Lactococcus lactis strain
which could serve as in vivo producer/secretor of IL-23 protein blockers into the
gut. To achieve this goal, we introduced ILP030, ILP317 and ILP323 cDNA sequences
into expression plasmid vector containing USP45 secretion signal, FLAG sequence
consensus and LysM-containing cA surface anchor (AcmA) ensuring cell-surface
peptidoglycan anchoring. We demonstrate that all ILP variants are expressed in L.
lactis cells, efficiently transported and secreted from the cell and displayed on
the bacterial surface. The binding function of AcmA-immobilized ILP proteins is
documented by interaction with a recombinant p19 protein, alpha subunit of human
IL-23, which was assembled in the form of a fusion with Thioredoxin A. ILP317
variant exhibits the best binding to the human IL-23 cytokine, as demonstrated
for particular L.lactis-ILP recombinant variants by Enzyme-Linked ImmunoSorbent
Assay (ELISA). We conclude that novel recombinant ILP-secreting L. lactis strains
were developed that might be useful for further in vivo studies of IL-23-mediated
inflammation on animal model of experimentally-induced colitis.
PMID- 29966385
TI - Macroscopic and Microscopic Properties of Some Surfactants and Biosurfactants.
AB - The adsorption of surfactants at the water-air and solid-water interfaces and
their wetting properties decide their practical applications. Therefore the
adsorption of monorhamnolipid, surfactin, n-octyl-β-d-glucopyranoside, n
dodecyl-β-d-glucopyranoside, n-dodecyl-β-d-maltoside, sucrose
monodecanoate, sucrose monododecanoate, Tween 20, Tween 60, and Tween 80 at the
water-air, polytetrafluoroethylene-water, polyethylene-water, poly(methyl
methacrylate)-water, polyamide-water, and quartz-water interfaces, their tendency
to form micelles as well as their wetting properties, were considered in the
light of their microscopic properties. For this purpose, the components and
parameters of the surfactant tail and head, water and solids surface tension, and
surfactant contactable area with adherent medium were applied for prediction of
surfactant-surfactant and surfactant-solid interactions through the water phase
with regard to their adsorption, micellization, and wetting processes. Next, the
Gibbs free energy of interactions was compared to the Gibbs free energy of
surfactant adsorption at the water-air and solid-water interfaces as well as the
micellization. It appeared that from the surfactant-surfactant and surfactant
solid interactions through the water phase determined on the basis of the tail
and head of surfactant surface tension, it is possible to predict the surfactant
tendency to adsorb at the water-air and solid-water interfaces, as well as to
form micelles.
PMID- 29966386
TI - Foreign-Trained Dentists in the United States: Challenges and Opportunities.
AB - The aim of the present study is to review the licensing process and challenges
faced by foreign-trained dentists in United States (U.S.), and how incorporating
foreign-trained dentists in the dental workforce in the U.S. impacts the
population’s dental care. Foreign-trained dentists must complete additional
training in a Commission of Dental Accreditation recognized program offered by a
U.S. dental school in order to be eligible for licensing. Foreign-trained
dentists interested in seeking employment in the U.S. face numerous challenges,
including stringent admission processes, high tuition costs, immigration barriers
and cultural differences. Opening the U.S. dental profession to foreign-trained
dentists provides several advantages, such as increasing the diversity of
dentists in the U.S., expanding access to underrepresented communities, and
enhancing the expertise of the profession. Foreign-trained dentists are an
important resource for a U.S. government seeking to build the human capital base
and make the most of global trade opportunities through a “brain
gain”. Increasing the diversity in the dental profession to match the
general U.S. population might improve access to dental care for minorities and
poor Americans, reducing disparities in dental care.
PMID- 29966387
TI - Electrochemically Enhanced Drug Delivery Using Polypyrrole Films.
AB - The delivery of drugs in a controllable fashion is a topic of intense research
activity in both academia and industry because of its impact in healthcare.
Implantable electronic interfaces for the body have great potential for positive
economic, health, and societal impacts; however, the implantation of such
interfaces results in inflammatory responses due to a mechanical mismatch between
the inorganic substrate and soft tissue, and also results in the potential for
microbial infection during complex surgical procedures. Here, we report the use
of conducting polypyrrole (PPY)-based coatings loaded with clinically relevant
drugs (either an anti-inflammatory, dexamethasone phosphate (DMP), or an
antibiotic, meropenem (MER)). The films were characterized and were shown to
enhance the delivery of the drugs upon the application of an electrochemical
stimulus in vitro, by circa (ca.) 10-30% relative to the passive release from non
stimulated samples. Interestingly, the loading and release of the drugs was
correlated with the physical descriptors of the drugs. In the long term, such
materials have the potential for application to the surfaces of medical devices
to diminish adverse reactions to their implantation in vivo.
PMID- 29966388
TI - ApoB-100 Lipoprotein Complex Formation with Intima Proteoglycans as a Cause of
Atherosclerosis and Its Possible Ex Vivo Evaluation as a Disease Biomarker.
AB - Experimental and clinical data indicate that the initiation and progress of
atherosclerosis and its clinical manifestations are first caused by circulating
apoB-100 lipoproteins that enter and are retained in the arterial intima.
Extracellular sulfated proteoglycans (PGs) of the intima are the retention
agents. The PGs also initiate physical and biochemical lipoprotein degradation
with the production of bioactive, lipid products that trigger an inflammatory
response that leads to atherosclerosis. There are many simple methods for
measuring abnormalities of circulating lipoproteins and their relation to
atherosclerotic cardiovascular disease (ACVD). However, limited research aims to
evaluate procedures that could report quantitatively about the contribution of
the interaction of apoB-100 lipoprotein-arterial intima PGs to clinical
manifestation of ACVD. In the present review we discuss observations indicating
that simple ex vivo evaluation of the affinity of apoB-100 lipoproteins for
arterial PGs and glycosaminoglycans (GAGs) can give an indication of its
association with clinical manifestations of atherosclerosis. In addition, we
discuss molecular and cellular aspects of the apoB-100 lipoproteins association
with arterial PGs that are related to atherogenesis and that support the
experimental framework behind the current “Response-to-Retention”
hypothesis of atherosclerosis.
PMID- 29966390
TI - Self-Controllable Secure Location Sharing for Trajectory-Based Message Delivery
on Cloud-Assisted VANETs.
AB - In vehicular ad hoc networks, trajectory-based message delivery is a message
forwarding strategy that utilizes the vehicle’s preferred driving routes
information to deliver messages to the moving vehicles with the help of roadside
units. For the purpose of supporting trajectory-based message delivery to a
moving vehicle, the driving locations of the vehicle need to be shared with
message senders. However, from a security perspective, vehicle users do not want
their driving locations to be exposed to others except their desired senders for
location privacy preservation. Therefore, in this paper, we propose a secure
location-sharing system to allow a vehicle user (or driver) to share his/her
driving trajectory information with roadside units authorized by the user. To
design the proposed system, we put a central service manager which maintains
vehicle trajectory data and acts as a broker between vehicles and roadside units
to share the trajectory data on the cloud. Nevertheless, we make the trajectory
data be hidden from not only unauthorized entities but also the service manager
by taking advantage of a proxy re-encryption scheme. Hence, a vehicle can control
that only the roadside units designated by the vehicle can access the trajectory
data of the vehicle.
PMID- 29966389
TI - Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of
Oxidative Stress and Clinical Perspective.
AB - Oxidative stress has been considered a key causing factor of liver damage induced
by a variety of agents, including alcohol, drugs, viral infections, environmental
pollutants and dietary components, which in turn results in progression of liver
injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver
fibrosis and cirrhosis. During the past 30 years and even after the major
progress in the liver disease management, millions of people worldwide still
suffer from an acute or chronic liver condition. Curcumin is one of the most
commonly used indigenous molecules endowed by various shielding functionalities
that protects the liver. The aim of the present study is to comprehensively
review pharmacological effects and molecular mechanisms, as well as clinical
evidence, of curcumin as a lead compound in the prevention and treatment of
oxidative associated liver diseases. For this purpose, electronic databases
including “Scopus,” “PubMed,” “Science
Direct” and “Cochrane library” were extensively searched with
the keywords “curcumin or curcuminoids” and “hepatoprotective
or hepatotoxicity or liver” along with “oxidative or oxidant.”
Results showed that curcumin exerts remarkable protective and therapeutic effects
of oxidative associated liver diseases through various cellular and molecular
mechanisms. Those mechanisms include suppressing the proinflammatory cytokines,
lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as
well as ameliorating cellular responses to oxidative stress such as the
expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself
acts as a free radical scavenger over the activity of different kinds of ROS via
its phenolic, β-diketone and methoxy group. Further clinical studies are
still needed in order to recognize the structure-activity relationships and
molecular mechanisms of curcumin in oxidative associated liver diseases.
PMID- 29966391
TI - The Effect of Training-Induced Visual Imageability on Electrophysiological
Correlates of Novel Word Processing.
AB - The concreteness effect (CE) describes a processing advantage for concrete over
abstract words. Electrophysiologically, the CE manifests in higher N400 and N700
amplitudes for concrete words. The contribution of the stimulus-inherent
imageability to the electrophysiological correlates of the CE is not yet fully
unraveled. This EEG study focused on the role of imageability irrespective of
concreteness by examining the effects of training-induced visual imageability on
the processing of novel words. In two training sessions, 21 healthy participants
learned to associate novel words with pictures of novel objects as well as
electron-microscopical structures and were additionally familiarized with novel
words without any picture association. During a post-training EEG session,
participants categorized trained novel words with or without picture association,
together with real concrete and abstract words. Novel words associated with novel
object pictures during the training elicited a higher N700 than familiarized
novel words without picture-association. Crucially, this training-induced N700
effect resembled the CE found for real words. However, a CE on the N400 was found
for real words, but no effect of imageability in novel words. The results suggest
that the N400 CE for real words depends on the integration of multiple semantic
features, while mere visual imageability might contribute to the CE in the N700
time window.
PMID- 29966392
TI - A Semantic Labeling Approach for Accurate Weed Mapping of High Resolution UAV
Imagery.
AB - Weed control is necessary in rice cultivation, but the excessive use of herbicide
treatments has led to serious agronomic and environmental problems. Suitable site
specific weed management (SSWM) is a solution to address this problem while
maintaining the rice production quality and quantity. In the context of SSWM, an
accurate weed distribution map is needed to provide decision support information
for herbicide treatment. UAV remote sensing offers an efficient and effective
platform to monitor weeds thanks to its high spatial resolution. In this work,
UAV imagery was captured in a rice field located in South China. A semantic
labeling approach was adopted to generate the weed distribution maps of the UAV
imagery. An ImageNet pre-trained CNN with residual framework was adapted in a
fully convolutional form, and transferred to our dataset by fine-tuning. Atrous
convolution was applied to extend the field of view of convolutional filters; the
performance of multi-scale processing was evaluated; and a fully connected
conditional random field (CRF) was applied after the CNN to further refine the
spatial details. Finally, our approach was compared with the pixel-based-SVM and
the classical FCN-8s. Experimental results demonstrated that our approach
achieved the best performance in terms of accuracy. Especially for the detection
of small weed patches in the imagery, our approach significantly outperformed
other methods. The mean intersection over union (mean IU), overall accuracy, and
Kappa coefficient of our method were 0.7751, 0.9445, and 0.9128, respectively.
The experiments showed that our approach has high potential in accurate weed
mapping of UAV imagery.
PMID- 29966394
TI - Electrochemical Deposition and Nucleation/Growth Mechanism of Ni-Co-Y2O3 Multiple
Coatings.
AB - Ni-Co alloy and Ni-Co-Y2O3 multiple coatings refined with nano-Y2O3 particles
were fabricated by ultrasonic-assisted electrochemical deposition in an acid
sulfamate bath. Linear sweep voltammetry (LSV), chronoamperometry (CA) and
electrochemical impedance spectroscopy (EIS) techniques were applied to
investigate the nucleation/growth process of composite coatings in co-deposition.
The LSV results indicated that the incorporation of nano-Y2O3 particles with the
Ni-Co matrix shifted the initial deposition potential to a more positive
potential and decreased cathodic polarization. For both coatings, the
nucleation/growth process approximately agreed with the Scharifker-Hill
instantaneous nucleation model. Nucleation parameters, including active
nucleation sites (N0) and nucleation rate (A) of the composite, were higher when
the measured potential range was between −1.05 V (vs. SCE) and −1.20
V vs. SCE, when compared with the Ni-Co alloy, and the observed AFM images of the
coatings were in good agreement with the calculated nucleation parameters (using
the Marquardt-Levenberg algorithm) of experimental curves. EIS testing indicated
that the charge transfer resistance of the composite was lower in
electrodeposition. The incorporation of nano-Y2O3 particles in the matrix changed
the preferred orientation of coatings and produced a more uniform and compact
deposit layer with finer grains.
PMID- 29966393
TI - Postnatal Development and Distribution of Sympathetic Innervation in Mouse
Skeletal Muscle.
AB - Vertebrate neuromuscular junctions (NMJs) have been conceived as tripartite
synapses composed of motor neuron, Schwann cell, and muscle fiber. Recent work
has shown the presence of sympathetic neurons in the immediate vicinity of NMJs
and experimental and clinical findings suggest that this plays an eminent role in
adult NMJ biology. The present study examined the postnatal development and
distribution of sympathetic innervation in different muscles using
immunofluorescence, confocal microscopy, and Western blot. This demonstrates the
proximity of sympathetic neurons in diaphragm, extensor digitorum longus,
tibialis anterior, soleus, and levator auris longus muscles. In extensor
digitorum longus muscle, sympathetic innervation of NMJs was quantified from
perinatal to adult stage and found to increase up to two months of age. In
diaphragm muscle, an extensive network of sympathetic neurons was prominent along
the characteristic central synapse band. In summary, these data demonstrate that
an elaborate sympathetic innervation is present in several mouse skeletal muscles
and that this is often next to NMJs. Although the presence of sympathetic neurons
at the perisynaptic region of NMJs increased during postnatal development, many
synapses were already close to sympathetic neurons at birth. Potential
implications of these findings for treatment of neuromuscular diseases are
discussed.
PMID- 29966395
TI - Determining the Glycaemic Index of Standard and High-Sugar Rodent Diets in
C57BL/6 Mice.
AB - The glycaemic index (GI) is a useful tool to compare the glycaemic responses of
foods. Numerous studies report the favorable effects of low GI diets on long term
metabolic health compared with high GI diets. However, it has not been possible
to link these effects to the GI itself because of other components such as
macronutrients and dietary fibre, which are known to affect GI. This study aimed
to create and evaluate isocaloric diets differing in GI independent of
macronutrient and fibre content. The GIs of eight diets differing in carbohydrate
source were evaluated in mice; cooked cornstarch (CC), raw cornstarch (RC), chow,
maltodextrin, glucose, sucrose, isomaltulose, and fructose. A glucose control was
also tested. The GIs of all eight diets were different from the GI of the glucose
control (GI: 100; p < 0.0001). The GIs of the glucose (mean +/- SEM: 52 +/- 3),
maltodextrin (52 +/- 6), CC (50 +/- 4), RC (50 +/- 6), and chow (44 +/- 4) diets
were similar, while the GIs of the sucrose (31 +/- 4), isomaltulose (24 +/- 5),
and fructose (18 +/- 2) diets were lower than all other diets (p < 0.05). This is
the first trial to report GI testing in vivo in mice, resulting in three main
findings: chow is relatively high GI, the glucose availability of raw and cooked
cornstarch is similar, and the GI of different sugar diets occur in the same rank
order as in humans.
PMID- 29966396
TI - Ionic Conductivity and Cycling Stability Improvement of PVDF/Nano-Clay Using PVP
as Polymer Electrolyte Membranes for LiFePO4 Batteries.
AB - In this paper, we present the characteristics and performance of polymer
electrolyte membranes (PEMs) based on poly(vinylidene fluoride) (PVDF). The
membranes were prepared via a phase-inversion method (non-solvent-induced phase
separation (NIPS)). As separators for lithium battery systems, additive modified
montmorillonite (MMT) nano-clay served as a filler and poly(vinylpyrrolidone)
(PVP) was used as a pore-forming agent. The membranes modified with an additive
(8 wt % nano-clay and 7 wt % PVP) showed an increased porosity (87%) and an
uptake of a large amount of electrolyte (801.69%), which generated a high level
of ionic conductivity (5.61 mS cm-1) at room temperature. A graphite/PEMs/LiFePO4
coin cell CR2032 showed excellent stability in cycling performance (average
discharge capacity 127 mA h g-minus;1). Based on these results, PEMs are
promising materials to be used in Polymer Electrolyte Membranes in lithium-ion
batteries.
PMID- 29966398
TI - A Low-Cost INS-Integratable GNSS Ultra-Short Baseline Attitude Determination
System.
AB - Traditional attitude determination using global navigation satellite system
(GNSS) carrier phases is mostly applied on geodetic-grade receivers with
sufficient baseline length. However, for some special applications such as mobile
communication base station smart antenna attitude determination, only low-cost
receivers with ultra-short baselines can be employed, and the environments are
more challenging. When solving the ambiguity resolution (AR) problem with low
cost receivers, it is hard for the traditional methods in ambiguity domain to
estimate float ambiguities accurately due to the large code pseudorange noises;
thus, such systems fail to determine the correct ambiguities. Aiming at improving
the AR success rate for ultra-short baselines attitude determination with low
cost receivers, we provide an objective function named Mean Square Residual (MSR)
based on the geometrical relationship among the position spherical search space,
the fractional carrier phases, and the possible ambiguities. The method can be
calculated without code pseudoranges, and thus, can provide a higher AR success
rate when using low-cost receivers. The corresponding analysis and acceptance
test method are discussed in this contribution, and further, as an extension for
more complicated urban dynamic applications, a GNSS/Inertial Navigation System
(INS) integrated system is introduced. Several experiments have been conducted to
verify performance.
PMID- 29966397
TI - Therapeutic Contact Lenses with Polymeric Vehicles for Ocular Drug Delivery: A
Review.
AB - The eye has many barriers with specific anatomies that make it difficult to
deliver drugs to targeted ocular tissues, and topical administration using eye
drops or ointments usually needs multiple instillations to maintain the
drugs’ therapeutic concentration because of their low bioavailability. A
drug-eluting contact lens is one of the more promising platforms for controllable
ocular drug delivery, and, among various manufacturing methods for drug-eluting
contact lenses, incorporation of novel polymeric vehicles with versatile features
makes it possible to deliver the drugs in a sustained and extended manner. Using
the diverse physicochemical properties of polymers for nanoparticles or implants
that are selected according to the characteristics of drugs, enhancement of
encapsulation efficiency and prolonged drug release are possible. Even though
therapeutic contact lenses with polymeric vehicles allow us to achieve sustained
ocular drug delivery, drug leaching during storage and distribution and the
possibility of problems related to surface roughness due to the incorporated
vehicles still need to be discussed before application in a real clinic. This
review highlights the overall trends in methodology to develop therapeutic
contact lenses with polymeric vehicles and discusses the limitations including
comparison to cosmetically tinted soft contact lenses.
PMID- 29966399
TI - Porous alpha-Fe2O3@C Nanowire Arrays as Flexible Supercapacitors Electrode
Materials with Excellent Electrochemical Performances.
AB - Porous α-Fe2O3 nanowire arrays coated with a layer of carbon shell have
been prepared by a simple hydrothermal route. The as-synthesized products show an
excellent electrochemical performance with high specific capacitance and good
cycling life after 9000 cycles. A solid state asymmetric supercapacitor (ASC)
with a 2 V operation voltage window has been assembled by porous α-Fe2O3/C
nanowire arrays as the anode materials, and MnO2 nanosheets as the cathode
materials, which gives rise to a maximum energy density of 30.625 Wh
kg−1and a maximum power density of 5000 W kg−1 with an excellent
cycling performance of 82% retention after 10,000 cycles.
PMID- 29966400
TI - Plant-Based Cannabinoids for the Treatment of Chronic Neuropathic Pain.
AB - Chronic neuropathic pain is a prevalent condition that places a heavy burden on
individuals and the healthcare system. Current medications have limitations and
new approaches are needed, particularly given the current opioid crisis. There is
some clinical evidence that the plant Cannabis sativa produces relief from
neuropathic pain. However, current meta-analyses suggest that this efficacy is
limited and there are problems with side effects. Most of this clinical research
has examined whole cannabis, the psychoactive phytocannabinoid 9
tetrahydrocannabinol (THC), and nabiximols, which are a mixture of THC and the
non-psychoactive phytocannabinoid cannabidiol. In the past, there has been little
evidence based, preclinical animal research to guide clinical studies on
phytocannabinoids. Recent animal studies indicate that while THC and high dose
nabiximols are effective in animal neuropathic pain models, significant pain
relief is only achieved at doses that produce substantial side effects. By
contrast, cannabidiol and low dose nabiximols have moderate pain relieving
efficacy, but are devoid of cannabinoid-like side effects. This animal data
suggests that cannabidiol and low dose nabiximols warrant consideration for
clinical studies, at least as adjuvants to current drugs. Preclinical research is
also required to identify other phytocannabinoids that have therapeutic
potential.
PMID- 29966402
TI - Ultrastructure of embryonic anal processes in Girardinichthys viviparus
(Cyprinodontiformes, Osteichthyes).
AB - Scanning and transmission electron microscopy were used to examine the morphology
of the perianal processes (trophotaeniae) of goodeid embryos (Girardinichthys
viviparus) at two stages of gestation. The epithelial surface of trophotaeniae is
composed of two cell types, one of which shows distinct features associated with
absorptive activity. Such cells are characterized by microvilli, abundant
mitochondria, and an agranular tubulolamellar network. Micropinocytosis at the
apical surface is relatively rare. The brush border membranes contain high levels
of alkaline phosphatase. The cells of the second type are the minor component of
the trophotaenial epithelium. Their surface is distinct, due to the presence of
microridges rather than microvilli. The reticulate arrangement of the cells gives
rise to intercellular spaces which occasionally are very large. These interstices
are populated with leukocytes. The histological appearance of these sections
indicates that this tissue is involved in gas exchange. Embryos at very early
stages of development possess similar epithelia which are differentiated to a
lesser extent. The connective tissue in some parts of the processes shows
structural modifications. It is densely packed with numerous leukocytes occupying
the spaces between the cytyoplasmic ramifications of the stroma cells. Possible
roles of the trophotaeniae in absorption, respiration, excretion, and the
acquisition of immunity are discussed, and it is concluded that the perianal
processes of the Goodeidae are more than just trophic embryonic structures.
PMID- 29966401
TI - Solid Wettability Modification via Adsorption of Antimicrobial Sucrose Fatty Acid
Esters and Some Other Sugar-Based Surfactants.
AB - Solid-liquid interface properties play a crucial role in the adsorption and
adhesion of different microorganisms to the solid. There are some methods to
inhibit microorganisms’ adsorption at the solid-liquid interface and their
adhesion to the solid. These methods can be divided into bulk phase and surface
modification. They are often based on the surfactants’ effect on the
wettability of the solid in a given system, due to the fact that adsorption and
wetting properties of the food additive antimicrobial surfactants (sucrose
monolaurate and sucrose monodecanoate as well as some other sugar-based ones (n
octyl-β-d-glucopyranoside, n-dodecyl-β-d- glucopyranoside, n-dodecyl
β-d-maltoside)) in the solid-aqueous solution of surfactant-air system were
considered. Quantitative description of adsorption of the studied compounds at
the solid-liquid interface was made based on the contact angle of the aqueous
solutions of studied surfactants on polytetrafluoroethylene, polyethylene,
poly(methyl methacrylate), polyamide and quartz surface and their surface
tension. From the above-mentioned considerations, it can be seen that during the
wettability process of the studied solids, surfactants are oriented in a specific
direction depending on the type of the solid and surfactant. This specific
orientation and adsorption of surfactant molecules at the solid-water interface
cause changes of the solid surface properties and its wettability, which was
successfully predicted in the studied systems.
PMID- 29966403
TI - Variations of the cephalic muscles in the colubrid snake genera Entechinus,
Opheodrys, and Symphimus.
AB - The cephalic muscles in three species of Entechinus, two species of Opheodrys,
and Symphimus mayae display patterns of interspecific variation that are largely
congruent with patterns of variation previously described for the skulls of these
species. This congruence does not stem from direct correlation between the shapes
of associated bones and muscles. In these colubrid snakes, most interspecific
variations in muscle form involve changes in the shape or relative position of
attachment points that appear unrelated to changes in the gross form of the bony
surfaces forming the attachment points and produce no major changes in the
architectural array of fibers in the muscle. Data presented here, combined with
information from previous comparative studies of colubroid cephalic muscles,
support the hypothesis that these muscles are limited in their potential
variability by factors favoring parallel arrangements of fibers.
PMID- 29966404
TI - Vascularization of a lobster muscle.
AB - The vascularization of the distal accessory flexor muscle (DAFM) in the walking
legs of the lobster, Homarus americanus, was examined with dye injection and
electron microscopy. Vascularization of this flat, thin DAFM is via two vessels,
one supplying the tendinal region of the muscle and the other the exoskeletal
region. The vessels that originate from the single major limb vessel, subdivide
extensively over the DAFM and form a profuse network that has hitherto gone
unnoticed. The degree of vascularization of individual fibers was determined by
periodic sampling along its length with thin-section electron microscopy. At each
and every sampling station, individual fibers had several (seven to eight), small
diameter (4 MUm) blood vessels in their cross-sectional profile. In contrast,
nerve terminals of the excitor and inhibitor axon were rarely encountered. This
high degree of vascularization was found amongst fibers that are from different
regions of the DAFM and differ in the performance of their excitatory synapse but
are similar in their structural and contractile properties.
PMID- 29966405
TI - Ultrastructure of the ileum of Locusta migratoria.
AB - The epithelium of the ileum of Locusta migratoria is composed of a single layer
of columnar cells surrounded on the luminal side by cuticle and on the haemocoel
side by a circular muscle layer. Where the circular muscles contact the
epithelium, longitudinal muscles are present and the epithelium is slightly
reduced. Elsewhere, a subepithelial sinus separates the epithelium from the
circular muscle layer. The epithelial cells are characterised by extensive
infoldings of the apical and basal cell membranes, which in the latter case,
produce a maze of interconnecting channels and spaces. Mitochondria are closely
associated with both apical and basal infoldings, although the bulk of these
organelles is located in the cytoplasm underlying the infoldings of the apical
plasma membrane. Vesicles of assorted sizes occur throughout the cytoplasm. They
are particularly abundant in the apical region, where they appear to be produced
by pinocytosis. Larger vesicles, containing either material of varying electron
density or smaller vesicles, occur in the medial and basal regions of the cells.
The contents of some of these vesicles have, in section, a lamellar appearance,
composed of concentric layers of material. Similar vesicles are present in the
basement membrane as well as the cells and connective tissue of the subepithelial
sinus. Microtubules and groups of ribosomes commonly occur throughout the
cytoplasm, and lipid-like droplets are also present in some of the cells.
Ultrastructural features of the epithelial cells are discussed in relation to
current knowledge of the function of the ileum.
PMID- 29966406
TI - Ultrastructure of duvernoy's gland from the wandering garter snake, Thamnophis
elegans vagrans (Serpentes, Colubridae).
AB - In addition to the supralabial glands (strips of glandular tissue lying along the
maxilla), most snakes of the family Colubridae possess an enlarged oral gland
lying behind the eye and emptying near the rear maxillary teeth, the Duvernoy's
gland. Duvernoy's gland is most probably homologous to the venom gland of viperid
and elapid snakes, and occasionally has been implicated in cases of human
envenomation. Although of possible medical concern, there is reason to believe
that secretion from this gland serves a biological role different from that of
the venom gland, namely a role primarily in digestion rather then largely in
rapid prey immobilization. The parenchyma of the Duvernoy's gland comprise two
cell types, a serous cell containing numerous, electron-dense secretory granules,
and myoepithelial cells. There are no mucous cells in the parenchyma; instead
cells of this type are located exclusively in the lining epithelium of the main
duct. Numerous unmyelinated nerves pass between secretory acini. Observations of
the supralabial gland reveal that this gland, in addition to serous cells, also
contains mucous cells and a putative third cell type we designate as an
intermediate cell. In cellular morphology, Duvernoy's gland is closest to the
venom gland of elapids, and least like the venom gland of viperids. Compared to
the venom glands in both families of venomous snakes, Duvernoy's gland lacks a
large luminal secretory reservoir. Emptying of Duvernoy's gland is thought to
involve release of secretion granules into the lumen, and movement of the
secretory product from there may be supplemented by mechanical pressure exerted
externally by nearby contracting striated mucles. These differences in structure
and mechanism of secretion release are taken as evidence that although they are
homologous, the two types of glands, Duvernoy's and venom glands, are
functionally distinct.
PMID- 29966407
TI - Ultrastructure of the body cavity lining in a secondary acoelomate,
Microphthalmus cf. Listensis westheide (Polychaeta: Hesionidae).
AB - The organization of the body cavity lining in selected regions of the juvenile
and adult of the interstitial hesionid polychaete Microphthalmus cf. listensis is
described. Tissues comprising the body cavity lining in the juvenile consist of
somatic and splanchnic circular and longitudinal muscles and undifferentiated
cells. Somatic and splanchnic cell layers exhibit epithelial ( = eucoelomate)
organization in the pharyngeal region. In the midbody, some undifferentiated
cells exhibiting mesenchymal organization persist among the epithelially
organized somatic and splanchnic cells, forming a gradation between eucoelomate
and acoelomate tissue organizations. A coelomic cavity is absent. Tissues
comprising the body cavity lining of the adult consist of somatic and splanchnic
circular and longitudinal myocytes and coelenchymal cells. Coelenchymal cells are
shown from serial section analysis to be mesenchymal in organization and derived
from the somatic peritoneum. A 30-65-nm coelomic cavity lies between the apices
of somatic and splanchnic cell layers in the pharyngeal region. In the anterior
setigerous segments, the coelom is reduced to a narrow cavity surrounded by
coelenchymal cells lying midventrally between the paired ejaculatory ducts. There
is a regional obliteration of the splanchnic musculature in the posterior
segments so that apices of the coelenchymal cells lie in direct apposition to the
basal extracellular matrix of the gut. The coeom is only present middorsally as a
0.7-MUm-wide cavity. Although the coelomic cavity is highly reduced in the adult,
the body cavity lining still reveals its origin from the epithelial ( =
eucoelomate) organization. The findings of this study illustrate possible
organizational intermediates in the evolution of the acoelomate from the
eucoelomate condition in annelids.
PMID- 29966408
TI - Ultrastructure of the dental epithelium and odontoblasts during enameloid matrix
deposition in cichlid teeth.
AB - Teleost enameloid matrix has been proposed to be an ectodermal, mesodermal, or
joint ectodermal-mesodermal product. To determine its origin we examined the
ultrastructure of the inner dental epithelium (IDE), odontoblasts, enameloid, and
dentin matrices of cichlid tooth buds at the stage of enameloid formation. (c)
Alan R. Liss, Inc. Columnar IDE cells had apical and basal terminal webs and
contained organelles associated with protein synthesis, including elongated
secretory granules containing fibrillar material having cross-striations with 60
nm periodicity. The morphology of IDE secretory granules was typical of
procollagen granules observed in a large variety of ectodermal and mesodermal
cells synthesizing collagen. In contrast, the paucity of secretory granules
within three odontoblast types indicates that these cells probably do not
synthesize enameloid matrix. These observations are consistent with the idea that
the bulk of the enameloid matrix is itself an ectodermal collagen synthesized and
secreted by IDE cells.
PMID- 29966409
TI - Ultrastructure and role of the lobster vas deferens in spermatophore formation:
The proximal segment.
AB - We have examined the anatomy of the vas deferens of the lobster Homarus
americanus and have described the structure of the proximal vas deferens
(segments one and two). The two tubes of segment one descend from the testes and
gradually merge into segment two. The epithelium of segment one has synthetic
activity and appears to contribute to the sperm-supporting matrix by exocytotic
release of granules through its apical surface. The epithelium of segment two is
also highly synthetic and secretes the primary spermatophore layer and part of
the intermediate layer that surround the sperm mass. The trifoil shape of the
extruded spermatophore is established through a change in height of some of the
cells lining the lumen in segment two. Connective tissue and circular bands of
striated muscle surround the epithelium of both segments.
PMID- 29966410
TI - Ultrastructure of spermatogenesis in the hawaiian red lobster, Enoplometopus
occidentalis (randall).
AB - Electron microscopy of spermatogenesis in the Hawaiian red lobster, Enoplometopus
occidentalis (Randall), has revealed unusual activity within membranous
organelles. Mitochondria-like bodies (MLB-1) seen first in spermatogonia appear
in primary spermatocytes to swell and fuse as the cytoplasm develops annulate
lamellae and other membrane complexes. In early spermatids, annulate lamellae
derived from the nuclear envelope contribute to development of an extensive
lamellar membrane complex within the cytoplasm, the forerunner of the lamellar
region. Other mitochondria-like bodies (MLB-2) originate from this membrane
complex and contribute to formation of the acrosomal vesicle, which assumes a
semicrystalline organization composed of bundles of tubular components slightly
larger in diameter than microtubules. An amorphous subacrosomal material may be
equivalent to the acrosomal tubule of other decapod spermatozoa. Centrioles at
the base of the acrosome produce microtubules that extend between the membranes
of the lamellar region distally through the uncondensed nucleus as the cores of
the three radial arms of this aflagellate spermatozoon. Nuclear material and
electron-dense lamellar region membranes project into the bases of these radial
arms. Nuclear and plasma membranes are fused except where the acrosome lies
between them. Of the mitochondria-like bodies, the MLB-1 do not persist into
spermiogenesis, and the MLB-2 are derived from the lamellar region. This is in
contrast with other reported studies of lobster spermatozoon ultrastructure.
PMID- 29966411
TI - Chlorine Dioxide-Pollutant Transformation and Formation of Hypochlorous Acid as a
Secondary Oxidant.
AB - Chlorine dioxide (ClO2) has been used as a disinfectant in water treatment for a
long time, and its use for micropollutant abatement in wastewater has recently
been suggested. Surprisingly, a mechanistic understanding of ClO2 reactions in
(waste)water matrices is largely lacking. The present study contributes to this
mechanistic understanding by performing a detailed investigation of ClO2
reactions with organic matter using phenol as a surrogate for reactive phenolic
moieties. A concept for indirectly determining HOCl using 2- and 4-bromophenol
was developed. The reaction of phenol with ClO2 formed chlorite (62 +/- 4% per
ClO2 consumed) and hypochlorous acid (HOCl) (42 +/- 3% per ClO2 consumed). The
addition of ClO2 to wastewater (5 * 10-5 M ClO2) resulted in 40% atenolol and 47%
metoprolol transformation. The presence of the selective HOCl scavenger glycine
largely diminished their transformation, indicating that atenolol and metoprolol
were transformed by a fast reaction with HOCl (e.g., k (atenolol + HOCl) = 3.5 *
104 M-1 s-1) that formed in ClO2 reactions with the wastewater matrix. The
formation of HOCl may thus increase the number of transformable micropollutants
in ClO2 applications. However, chlorine related byproducts may also be formed.
PMID- 29966412
TI - Replica-Based Protein Structure Sampling Methods: Compromising between Explicit
and Implicit Solvents.
AB - The structure of a protein is often not completely accessible by experiments. In
silico, replica exchange molecular dynamics (REMD) is the standard sampling
method for predicting the secondary and tertiary structures from the amino acid
sequence, but it is computationally very expensive. Two recent adaptations from
REMD, temperature intervals with global exchange of replicas (TIGER2) and
TIGER2A, have been tested here in implicit and explicit solvents. Additionally,
explicit, implicit, and hybrid solvent REMD are compared. On the basis of the
hybrid REMD (REMDh) method, we present a new hybrid TIGER2h algorithm for faster
structural sampling, while retaining good accuracy. The implementations of REMDh,
TIGER2, TIGER2A, and TIGER2h are provided for nanoscale molecular dynamics
(NAMD). All the methods were tested with two model peptides of known structure,
(AAQAA)3 and HP7, with helix and sheet motifs, respectively. The TIGER2 methods
and REMDh were also applied to the unknown structure of the collagen type I
telopeptides, which represent bigger proteins with some degree of disorder. We
present simulations covering more than 180 MUs and analyze the performance and
convergence of the distributions of states between the particular methods by
dihedral principal component and secondary structure analysis.
PMID- 29966413
TI - High Thermoelectric Performance in Crystallographically Textured n-Type Bi2Te3-
xSe x Produced from Asymmetric Colloidal Nanocrystals.
AB - In the present work, we demonstrate crystallographically textured n-type Bi2Te3-
xSe x nanomaterials with exceptional thermoelectric figures of merit produced by
consolidating disk-shaped Bi2Te3- xSe x colloidal nanocrystals (NCs).
Crystallographic texture was achieved by hot pressing the asymmetric NCs in the
presence of an excess of tellurium. During the hot press, tellurium acted both as
lubricant to facilitate the rotation of NCs lying close to normal to the pressure
axis and as solvent to dissolve the NCs approximately aligned with the pressing
direction, which afterward recrystallize with a preferential orientation. NC
based Bi2Te3- xSe x nanomaterials showed very high electrical conductivities
associated with large charge carrier concentrations, n. We hypothesize that such
large n resulted from the presence of an excess of tellurium during processing,
which introduced a high density of donor TeBi antisites. Additionally, the
presence in between grains of traces of elemental Te, a narrow band gap
semiconductor with a work function well below Bi2Te3- xSe x, might further
contribute to increase n through spillover of electrons, while at the same time
blocking phonon propagation and hole transport through the nanomaterial. NC-based
Bi2Te3- xSe x nanomaterials were characterized by very low thermal conductivities
in the pressing direction, which resulted in ZT values up to 1.31 at 438 K in
this direction. This corresponds to a ca. 40% ZT enhancement from commercial
ingots. Additionally, high ZT values were extended over wider temperature ranges
due to reduced bipolar contribution to the Seebeck coefficient and the thermal
conductivity. Average ZT values up to 1.15 over a wide temperature range, 320 to
500 K, were measured, which corresponds to a ca. 50% increase over commercial
materials in the same temperature range. Contrary to most previous works, highest
ZT values were obtained in the pressing direction, corresponding to the c
crystallographic axis, due to the predominance of the thermal conductivity
reduction over the electrical conductivity difference when comparing the two
crystal directions.
PMID- 29966414
TI - Doped Argon Surface Desorption Dielectric-Barrier Discharge Ionization Mass
Spectrometry for Fragile Compounds.
AB - Argon surface desorption dielectric-barrier discharge ionization (Ar-SDDBDI) in
conjunction with dopants was reported for rapid and sensitive determining of
fragile compounds. In dopant/Ar-SDDBDI, analytes are ionized primarily through
proton transfer with dopant ions, which are formed in Ar plasma. Different from
He, dopant/Ar-SDDBDI generates low energetic ions, and therefore, fragmentation
is suppressed. It thus significantly simplifies the mass spectra and the
assignment of one peak. Dopants ranging from organic solvents to gaseous
materials were systematically studied. The application of dopant/Ar-SDDBDI was
demonstrated by analysis of multiple compounds, including antibiotics, amino
acids, fatty acids, hormones, pharmaceuticals, and peptides. Rapid profiling of
chemicals in such complex matrixes including mixtures and drug tablets was also
tested. Positive and negative mass spectra with little to no fragmentation for
compounds in the pure state and as mixtures were readily achieved. Limits of
detection (S/N = 3) were determined to be 0.60 and 0.36 pmol, respectively, for
the analysis of l-alanine and metronidazole. Furthermore, the demonstration
applications also included imaging of an "H" character under ambient conditions.
These results indicate that the technique by combining of Ar-SDDBDI with dopants
exhibits high sensitivity, high spatial resolution, and a very low degree of
fragmentation, which render it a potential tool for fragile compound analysis in
mass spectrometry imaging.
PMID- 29966415
TI - Reverse Multidrug Resistance in Human HepG2/ADR by Anti-miR-21 Combined with
Hyperthermia Mediated by Functionalized Gold Nanocages.
AB - Multidrug resistance (MDR) remains a formidable challenge to effective clinical
cancer therapy. Herein, a nonviral gene delivery system HA/anti-miR-21/PPAuNCs to
overcome MDR was reported. This system could condense the microRNA-21 inhibitor
(anti-miR-21) into hyaluronic acid-conjugated and polyethylenimine-modified
PEGylated gold nanocages (AuNCs) and had good stability. In vitro studies
demonstrated that HA/anti-miR-21/PPAuNCs could enhance intracellular DOX
accumulation in DOX-resistant HCC cells (HepG2/ADR cells) and increase the
sensitivity to DOX of HepG2/ADR cells through upregulating PTEN protein
expression mediated by anti-miR-21 and downregulating P-gp protein expression
mediated by the hyperthermia of HA/PPAuNCs upon mild near-infrared irradiation.
Furthermore, the therapeutic effects had been enhanced due to the combination of
chemotherapy, gene therapy, and photothermal therapy. Besides, HA/anti-miR
21/PPAuNCs have a good biocompatibility. These findings can provide new insights
and strategies for the treatment of cancers with MDR.
PMID- 29966416
TI - Photosensitizer-Encapsulated Ferritins Mediate Photodynamic Therapy against
Cancer-Associated Fibroblasts and Improve Tumor Accumulation of Nanoparticles.
AB - Nanoparticles have been widely tested as drug delivery carriers or imaging
agents, largely because of their ability to selectively accumulate in tumors
through the enhanced permeability and retention (EPR) effect. However, studies
show that many tumors afford a less efficient EPR effect and that many
nanoparticles are trapped in the perivascular region after extravasation and
barely migrate into tumor centers. This is to a large degree attributed to the
dense tumor extracellular matrix (ECM), which functions as a physical barrier to
prevent efficient nanoparticle extravasation and diffusion. In this study, we
report a photodynamic therapy (PDT) approach to enhance tumor uptake of
nanoparticles. Briefly, we encapsulate ZnF16Pc, a photosensitizer, into ferritin
nanocages, and then conjugate to the surface of the ferritin a single chain
viable fragment (scFv) sequence specific to fibroblast activation protein (FAP).
FAP is a plasma surface protein widely upregulated in cancer-associated
fibroblasts (CAFs), which is a major source of the ECM fiber components. We found
that the scFv-conjugated and ZnF16Pc-loaded ferritin nanoparticles (scFv-Z@FRT)
can mediate efficient and selective PDT, leading to eradication of CAFs in
tumors. When tested in bilateral 4T1 tumor models, we found that the tumor
accumulation of serum albumin (BSA), 10 nm quantum dots (QDs), and 50 nm QDs was
increased by 2-, 3.5-, and 18-fold after scFv-Z@FRT mediated PDT. Our studies
suggest a novel and safe method to enhance the delivery of nanoparticles to
tumors.
PMID- 29966417
TI - Gold-Catalyzed Post-Ugi Ipso-Cyclization with Switchable Diastereoselectivity.
AB - A gold-catalyzed post-Ugi ipso-cyclization for the diastereoselective synthesis
of spirocyclic pyrrol-2-one-dienone system is described. Tuning the catalytic
system, solvent, and temperature allowed selectively attaining two sets of
diastereoisomers. The scope of the process has been evaluated, and a putative
mechanistic model was proposed.
PMID- 29966418
TI - Demulsification of Oil-in-Water (O/W) Emulsion in Bidirectional Pulsed Electric
Field.
AB - The research about electric demulsification of oil-in-water (O/W) emulsion is not
enough at present, especially compared with that about electric demulsification
of water-in-oil (W/O) emulsion. As an easy and novel method, a bidirectional
pulsed electric field (BPEF) was investigated to demulsify the O/W emulsion in
this work. Here we report that BPEF could actuate O/W emulsion to form rotational
flow and drove oil droplets to form oil-droplet chains and to coalescence. In
order to interpret the mutual attraction and coalescence of oil drops in BPEF, we
put forward the hypothesis that charges on an oil drop surface would redistribute
in BPEF, and we built the charge redistribution model according to the adsorption
phenomenon of oil droplets. The behavior of oil drops in BPEF could be
successfully explained in terms of the hypothesis and the model. The charge
redistribution on an oil droplet surface could be evaluated by the two parameters
we proposed. An amended potential redistribution formula of an oil drop surface
was also obtained according to the model. The O/W emulsions were successfully
demulsified by BPEF in the experiments. It showed that BPEF could be a
significant method for electric demulsification of O/W emulsions.
PMID- 29966419
TI - Classical Drude Polarizable Force Field Model for Methyl Phosphate and Its
Interactions with Mg2.
AB - Phosphate groups are essential components of nucleic acids and proteins, whose
interactions with solvent, metal ions, and ionic side chains help control folding
and binding. Methyl phosphate (MP) represents a simple analog of phosphate
moieties that are post-translation modifications in proteins and present at the
termini of nucleic acids, among other environments. In the present study, we
optimized parameters for use in polarizable molecular dynamics simulations of MP
in its mono- and dianionic forms, MP- = CH3HPO4- and MP2- = CH3PO42-, along with
P i2- = HPO42-, in the context of the classical Drude oscillator model. Parameter
optimization was done in a manner consistent with the remainder of the Drude
molecular mechanics force field, choosing atomic charges and polarizabilities to
reproduce molecular properties from quantum mechanics as well as experimental
hydration free energies. Optimized parameters were similar to existing dimethyl
phosphate parameters, with a few significant differences. The developed
parameters were then used to compute magnesium binding affinities in aqueous
solution, using alchemical molecular dynamics free energy simulations. Good
agreement with experiment was obtained, and outer sphere binding was shown to be
predominant for MP- and MP2-.
PMID- 29966420
TI - Development of a Janus Kinase Inhibitor Prodrug for the Treatment of Rheumatoid
Arthritis.
AB - While highly efficacious in treating rheumatoid arthritis (RA), the approved
Janus kinase (JAK) inhibitor, Tofacitinib (Tofa, CP-690 550), has dose-dependent
toxicities that limit its clinical application. In this study, we have examined
whether a prodrug design that targets arthritic joints would enhance Tofa's
therapeutic efficacy, which may provide an opportunity for future development of
safer Tofa dosing regimens. A prodrug of Tofa (P-Tofa) was synthesized by
conjugating the drug to the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer
via an acid cleavable carbamate linker. The therapeutic efficacy of a single dose
of P-Tofa was compared to the dose-equivalent daily oral administration of Tofa
in an adjuvant-induced arthritis (AA) rat model. Saline treated AA rats and age
matched healthy rats were used as controls. Observational analyses support the
superior and sustained efficacy of a single dose P-Tofa treatment compared to the
dose-equivalent daily Tofa administration in ameliorating joint inflammation.
Micro-CT and histological analyses demonstrated that the P-Tofa treatment
provided a structural preservation of the joints better than that of the dose
equivalent Tofa. Optical imaging, immunohistochemistry, and fluorescence
activated cell sorting analyses attribute P-Tofa's superior therapeutic efficacy
to its passive targeting to arthritic joints and inflammatory cell-mediated
sequestration. In vitro cell culture studies reveal that the P-Tofa treatment
produced sustained the inhibition of JAK/STAT6 signaling in IL-4-treated murine
bone marrow macrophages, consistent with a gradual subcellular release of Tofa.
Collectively, a HPMA-based nanoscale prodrug of P-Tofa has the potential to
enhance the therapeutic efficacy and widen the therapeutic window of Tofa therapy
in RA.
PMID- 29966422
TI - Strategic C to N Replacement in beta-Peptides: Atomic Level Control of Helical
Folding.
AB - Single residue control of the helical topology of beta-peptides is a contemporary
challenge in foldamer science. We present the conformational preferences of
oligomers of trans-2-aminocyclobutanecarboxylic acid ( tACBC), in which a central
residue has been replaced by a single N-aminoazetidine-2-carboxylic acid (AAzC)
moiety. The latter has such a strong demand for local 8-helical conformers that
the usual 12-helix secondary structure of a tACBC octamer is switched to a fully
8-helical conformation as a result of the single residue substitution.
PMID- 29966421
TI - Similar Albeit Not the Same: In-Depth Analysis of Proteoforms of Human Serum,
Bovine Serum, and Recombinant Human Fetuin.
AB - Fetuin, also known as alpha-2-Heremans Schmid glycoprotein (AHSG), belongs to
some of the most abundant glycoproteins secreted into the bloodstream. In blood,
fetuins exhibit functions as carriers of metals and small molecules. Bovine
fetuin, which harbors 3 N-glycosylation sites and a suggested half dozen O
glycosylation sites, has been used often as a model glycoprotein to test novel
analytical workflows in glycoproteomics. Here we characterize and compare fetuin
in depth, using protein from three different biological sources: human serum,
bovine serum, and recombinant human fetuin expressed in HEK-293 cells, with the
aim to elucidate similarities and differences between these proteins and the post
translational modifications they harbor. Combining data from high-resolution
native mass spectrometry and glycopeptide centric LC-MS analysis, we
qualitatively and quantitatively gather information on fetuin protein maturation,
N-glycosylation, O-glycosylation, and phosphorylation. We provide direct
experimental evidence that both the human serum and part of the recombinant
proteins are processed into two chains (A and B) connected by a single interchain
disulfide bridge, whereas bovine fetuin remains a single-chain protein. Although
two N-glycosylation sites, one O-glycosylation site, and a phosphorylation site
are conserved from bovine to human, the stoichiometry of the modifications and
the specific glycoforms they harbor are quite distinct. Comparing serum and
recombinant human fetuin, we observe that the serum protein harbors a much
simpler proteoform profile, indicating that the recombinant protein is not
ideally engineered to mimic human serum fetuin. Comparing the proteoform profile
and post-translational modifications of human and bovine serum fetuin, we observe
that, although the gene structures of these two proteins are alike, they
represent quite distinct proteins when their glycoproteoform profile is also
taken into consideration.
PMID- 29966423
TI - A Mechanistic Model for the Aziridine Aldehyde-Driven Macrocyclization of
Peptides.
AB - Aziridine aldehyde-driven macrocyclization of peptides is a powerful tool for the
construction of biologically active macrocycles. While this process has been used
to generate diverse collections of cyclic molecules, its mechanistic
underpinnings have remained unclear. To enable progress in this area we have
carried out a mechanistic study, which suggests that the cyclization owes its
efficiency to a combination of electrostatic attraction between the termini of a
nitrilium ion intermediate and intramolecular hydrogen bonding. Our model
adequately explains the experimentally observed trends, including
diastereoselectivity, and should facilitate the development of other
macrocyclization reactions.
PMID- 29966424
TI - Investigation of Receptor-Mediated Cyanocobalamin (Vitamin B12) Transport across
the Inner Blood-Retinal Barrier Using Fluorescence-Labeled Cyanocobalamin.
AB - The blood-to-retina supply of cyanocobalamin (vitamin B12) across the blood
retinal barrier (BRB) was investigated by synthesizing a fluorescence-labeled
cyanocobalamin (Cy5-cyanocobalamin). In the in vivo analysis following internal
jugular injection of Cy5-cyanocobalamin, confocal microscopy showed the
distribution of Cy5-cyanocobalamin in the inner plexiform layer (IPL), the outer
plexiform layer (OPL), and the retinal pigment epithelium (RPE). In the in vitro
analysis with TR-iBRB2 cells, an in vitro model cell line of the inner BRB, Cy5
cyanocobalamin uptake by TR-iBRB2 cells exhibited a time-dependent increase after
preincubation with transcobalamin II (TCII) protein, during its residual uptake
without preincubation with TCII protein. The Cy5-cyanocobalamin uptake by TR
iBRB2 cells was significantly reduced in the presence of unlabeled
cyanocobalamin, chlorpromazine, and chloroquine and was also significantly
reduced under Ca2+-free conditions. Confocal microscopy of the TR-iBRB2 cells
showed fluorescence signals of Cy5-cyanocobalamin and GFP-TCII protein, and these
signals merged with each other. The RT-PCR, Western blot, and
immunohistochemistry clearly suggested the expression of TCII receptor (TCII-R)
in the inner and outer BRB. These results suggested the involvement of receptor
mediated endocytosis in the blood-to-retina transport of cyanocobalamin at the
inner BRB with implying its possible involvement at the outer BRB.
PMID- 29966425
TI - Stereodivergent Synthesis of 3-Aminooxindole Derivatives Containing Vicinal
Tetrasubstituted Stereocenters via the Mannich Reaction.
AB - A highly enantioselective stereodivergent synthesis of 3-aminooxindole
derivatives was accomplished via asymmetric Mannich reaction between 2
substituted benzofuran-3-one and isatin-derived ketimines. Both anti and syn
selective chiral 3,3-disubstituted amino oxindoles bearing two adjacent
tetrasubstituted stereogenic centers with high yield and excellent
enantioselectivities were obtained using readily available cinchona-alkaloid
derived organocatalysts. The control experiment revealed that oxygen atom present
in the benzofuran ring played an important role in switching diastereodivergence.
The obtained Mannich product was further transformed into a biologically
important 2,3-dihydrobenzofuran derivative having three contiguous stereocenters
with no loss of enantioselectivity.
PMID- 29966426
TI - Renegotiating relationships: Theorising shared experiences of dementia within the
dyadic career.
AB - The dyad is increasingly recognised as a key site of experiences of dementia, yet
theoretical accounts of the dyad remain poor; 21st-century political developments
regarding dementia have changed the ways in which the dyad is perceived, from the
carer as victim to the person with dementia as victim. Across both approaches, a
problematic dichotomy of two individuals remains. The concept of 'joint career',
developed from Goffman's 'moral career', offers an alternative approach to shared
dyadic experiences of dementia. Using data from interviews with people affected
by dementia regarding their experiences of dementia, this paper presents an
account of the dyadic career, a patterned trajectory of shared experience. The
introduction of dementia into pre-existing dyads entails the renegotiation of
longstanding roles. As role transformation progresses, increasing difficulties
lead to the creation of symbolic boundaries denoting the limits of the care-giver
role. When those boundaries are encountered, they are often transgressed, and the
dyadic career hardens as it continues, becoming work-like and less affective.
This hardening of relationships is grounded in nihilism, apprehension and
objectification.
PMID- 29966427
TI - Adult Children's Relationship to Parent Influences Their Views on Aging and
Attitude Toward Own Aging.
AB - The goal of this study was to examine how the quality of relationship between
parent and adult children influences adult children's views on aging and attitude
toward their own aging and whether the effects of relationship qualities depend
on parents' health and adult children's perceptions of how well their parents
were aging. The sample included 217 adult children aged 18 to 73. Findings
revealed that different parent-child relationship quality dimensions (i.e.,
support, conflict, depth, ambivalence) differentially influenced adult children's
view on aging (positive and negative) and attitude toward own aging, and some of
these effects depended on levels of parental health and the way adult children
view how successfully their parents were aging. The quality of the relationship
to one's parents has an important role in shaping adults' views on aging and
experience of their own aging, highlighting the importance of incorporating the
role of family context to further enhance our understanding of how individuals
develop perceptions of aging.
PMID- 29966428
TI - Similar weight loss and maintenance in African American and White women in the
Improving Weight Loss (ImWeL) trial.
AB - OBJECTIVE: African Americans (AA) are often underrepresented and tend to lose
less weight than White participants during the intensive phase of behavioral
obesity treatment. Some evidence suggests that AA women experience better
maintenance of lost weight than White women, however, additional research on the
efficacy of extended care programs (i.e. continued contacts to support the
maintenance of lost weight) is necessary to better understand these differences.
METHODS: The influence of race on initial weight loss, the likelihood of
achieving >=5% weight reduction (i.e. extended care eligibility), the maintenance
of lost weight and extended care program efficacy was examined in 269 AA and
White women (62.1% AA) participating in a 16-month group-based weight management
program. Participants achieving >=5% weight reduction during the intensive phase
(16 weekly sessions) were randomized to a clustered campaign extended care
program (12 sessions delivered in three, 4-week clusters) or self-directed
control. RESULTS: In adjusted models, race was not associated with initial weight
loss (p = 0.22) or the likelihood of achieving extended care eligibility (odds
ratio 0.64, 95% CI [0.29, 1.38]). AA and White women lost -7.13 +/- 0.39 kg and
7.62 +/- 0.43 kg, respectively, during initial treatment. There were no
significant differences in weight regain between AA and White women (p = 0.64)
after adjusting for covariates. Clustered campaign program participants (AA:
6.74 +/- 0.99 kg, White: -6.89 +/- 1.10 kg) regained less weight than control
(AA: -5.15 +/- 0.99 kg, White: -4.37 +/- 1.04 kg), equating to a 2.12 kg (p =
0.03) between-group difference after covariate adjustments. CONCLUSIONS: Weight
changes and extended care eligibility were comparable among all participants. The
clustered campaign program was efficacious for AA and White women. The high
representation and retention of AA participants may have contributed to these
findings.
PMID- 29966429
TI - Clinically recorded heart rate and incidence of 12 coronary, cardiac,
cerebrovascular and peripheral arterial diseases in 233,970 men and women: A
linked electronic health record study.
AB - Background In healthy population cohorts, resting heart rate above 90 bpm is
associated with mortality from coronary heart disease, but it is not clear
whether associations are present at lower heart rates or whether these
associations differ between women. Methods The CALIBER resource of linked
electronic health records from primary care, hospitalisations, myocardial
infarction registry and cause-specific mortality in the UK was used to assess
associations between resting heart rate and 12 fatal and non-fatal coronary,
cardiac, cerebral and peripheral vascular cardiovascular diseases and death using
Cox proportional hazard models. Results Among 233,970 patients, 29,690 fatal and
non-fatal events occurred. Fully adjusted models showed that resting heart rate
was not associated in men or women with cerebrovascular events. In men a resting
heart rate of 70-79 bpm (29.1% of all men) versus less than 60 bpm was associated
with an increased risk of heart failure (hazard ratio (HR) 1.65, 95% confidence
interval (CI) 1.26-2.16), unheralded coronary death (HR 1.65, 95% CI 1.13-2.41),
total cardiovascular events (HR 1.22, 95% CI 1.15-1.28) and all-cause mortality
(HR 1.39, 95% CI 1.22-1.58). Women with a higher resting heart rate level of 80
89 bpm versus 60 bpm had a higher risk of total cardiovascular disease events (HR
1.17, 95% CI 1.07-1.24) and all-cause mortality (HR 1.21, 95% CI 1.07-1.35)
compared to a resting heart rate less than 60 bpm. The risk was also present at
higher heart rates (>90 bpm) for heart failure and sudden cardiac death.
Conclusions A resting heart rate that clinicians currently consider as 'normal'
in the general population is specifically associated with the incidence of
certain major cardiovascular diseases and death, with the risk starting at lower
resting heart rate levels in men compared to women. Further research is required
to evaluate whether interventions to lower resting heart rate are warranted to
prevent disease. The study is registered at: clinicaltrials.gov (ID:
NCT01947361).
PMID- 29966430
TI - Evaluation of reproducibility in MRI quantitative volumetric assessment and its
role in the prediction of overall survival and progression-free survival in
glioblastoma.
AB - Background Residual tumor volume (RTV) and extent of resection (EOR) have
previously been shown to affect survival in glioblastoma (GB) patients.
Quantitative radiological assessment (QRA) of these factors could potentially
affect clinical decision-making in the postoperative period. Purpose The first
aim was to evaluate the reproducibility of different volume estimation methods of
RTV and EOR by comparing QRA with subjective visual estimation and with objective
volume estimations. The second aim was to clarify whether QRA of RTV and EOR
would provide accuracy in predicting progression-free survival (PFS) and overall
survival (OS) in GB patients. Material and Methods Seventy GB patients were
studied retrospectively. Reproducibility of QRA was compared to conventional
visual analysis. Intra-rater agreement between two repeated measurements of 25
patients was calculated. QRA for RTV and EOR was made for the entire study
population. Survival analysis was performed by multivariate cox-regression
analysis. Results QRA of RTV and EOR gave superior intra-rater agreement compared
to subjective evaluation. Multivariate survival analysis showed prognostic
significance on 18 months PFS (hazard ratio [HR] = 0.44, P = 0.003) and OS (HR =
0.42, P = 0.012) at RTV < 1.6 mL and with EOR > 96% on PFS (HR = 2.152, P =
0.005) but not on OS (HR = 1.92, P = 0.053). Conclusion QRA of tumor volumes is
more robust compared to standard evaluation methods. Since EOR and RTV are
correlated to the prognosis in GB, quantitative analysis of tumor volumes could
aid decision-making and patient management postoperatively.
PMID- 29966431
TI - A Person-Centered Analysis of Motivation for Physical Activity and Perceived
Neighborhood Environment in Residents of Assisted Living Facilities.
AB - This study sought to identify profiles of individual, social, and perceived
neighborhood environmental correlates of physical activity (PA) and to explore
differences between the identified profiles in PA. Residents of assisted living
facilities ( N = 87, M age = 77.57 years) were recruited for the cross-sectional
study. Participants reported their perceived support from important others for
PA, basic psychological need satisfaction and motivation for PA, and perceived
neighborhood environment around the assisted living facilities. Engagement in
light PA and moderate-to-vigorous PA was measured by accelerometers over 1 week.
We identified three profiles using latent profile analysis: 'low self-determined
and minimally supported', 'moderately self-determined and supported', and 'highly
self-determined and supported'. Results showed participants in the highly self
determined and supported profile engaged in higher levels of light PA and
moderate-to-vigorous PA than participants from other profiles. Findings showed
perceptions of the neighborhood environment should be taken into account with
motivation regarding PA.
PMID- 29966432
TI - Socioeconomic factors associated with diet quality and meeting dietary guidelines
in disadvantaged neighborhoods in the Southeast United States.
AB - OBJECTIVE: To examine diet quality and dietary intake among residents of
disadvantaged neighborhoods in the Southeast United States (U.S.) and to examine
associations between dietary and socioeconomic factors. DESIGN: We examined
baseline data from an evaluation study of a healthy food access initiative.
Participants were recruited from two urban settings comprising seven
neighborhoods of high household poverty (17% to 62%). Participants completed in
person interviews with measures of education, household income, and food security
and one unannounced 24-hour dietary recall by telephone with trained registered
dietitians. Food desert residence was coded based on U.S. Census data.
Proportions meeting 2010 Dietary Guidelines for Americans and Healthy Eating
Index 2010 (HEI-2010) scores were computed. Associations between dietary
variables and participant's education, household income, food security, and food
desert residence were tested. RESULTS: Participants (n = 465) were predominantly
African American (92%), women (80%), and overweight or obese (79%), and 52 +/- 14
years of age. Sixty-three percent had low or very low food security, and 82%
lived in census tracts of low income and low access to supermarkets (urban food
desert). HEI-2010 scores averaged 48.8 +/- 13.1. A minority of participants met
dietary guidelines. Diet quality was lower among participants with lower
education and among those from food insecure households (p < .05). Household
income and food security were positively associated with meeting several dietary
guidelines (p < .05). Food desert residence was unrelated to diet variables.
CONCLUSIONS: In this disadvantaged population, significant nutritional concerns
were observed, and socioeconomic factors were associated with diet quality and
meeting dietary guidelines. Interventions must address broader economic, social,
and policy issues such as access to affordable healthy foods.
PMID- 29966433
TI - Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory
activity on tubulin polymerization.
AB - AIM: Discovery of novel series of colchicine binding site inhibitors (CBSIs).
MATERIALS & METHODS: Isoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f,
cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and
evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most
of the compounds displayed potent to moderate antitumor activity against leukemia
SR cell line.7c, 7e and 11a were more potent than colchicine with IC50 of 0.09,
0.05 and 0.06 MUM, and percentage inhibition in tubulin polymerization of 95.2,
96.0 and 96.3%, respectively. Compounds 7c and 11a showed cell-cycle arrest at
G2/M phase and induced apoptosis and were able to bind the colchicine binding
site of tubulin with comparable affinity to colchicine. Docking study showed that
these compounds may interact with tubulin exploiting a binding cavity not
commonly reported in the binding of CBSI. CONCLUSION: Compounds 7c and 11a may be
considered as promising CBSI based on their excellent activity and favorable drug
likeness profile.
PMID- 29966434
TI - Mediterranean diet, active lifestyle and cardiovascular disease: A recipe for
immortality?
PMID- 29966435
TI - Global longitudinal strain measured by speckle tracking identifies subclinical
heart involvement in patients with systemic sclerosis.
AB - Background Systemic sclerosis is characterised by progressive cutaneous and organ
fibrosis. Among all organs, a subclinical heart involvement is difficult to
detect through conventional imaging. Design We evaluated whether speckle tracking
derived global longitudinal strain could help detect early subclinical systolic
dysfunction in systemic sclerosis patients without overt clinical involvement.
Methods A case-control, single-centre study on 52 systemic sclerosis patients and
52 age and gender-matched controls. Patients with structural heart disease, heart
failure, atrial fibrillation and pulmonary hypertension were excluded. For every
patient, standard echocardiographic and speckle tracking-derived variables for
the systolic and diastolic function of the left ventricle and right ventricle
were acquired. Results Traditional parameters of left and right systolic function
did not differ between systemic sclerosis patients and controls (all P = ns).
Left and right ventricular global longitudinal strain was significantly impaired
in patients with systemic sclerosis when compared to controls (-19.2% vs. -21.1%;
P = 0.009 and -18.2% vs. -22.3%; P = 0.012, respectively). Systemic sclerosis
patients had a 2.5-fold increased risk of subclinical left ventricular systolic
impairment (odds ratio 2.5, 95% confidence interval 1.1-5.5; P = 0.027) and a 3.3
fold increased risk of subclinical right ventricular systolic impairment when
compared to controls (odds ratio 3.3, 95% confidence interval 1.4-7.7; P =
0.004). Alterations in the myocardial deformation pattern of systemic sclerosis
patients were homogeneous in the right ventricle and eccentric in the left
ventricle. Conclusions While traditional echocardiographic parameters are
ineffective in detecting subclinical systolic impairment, reduced global
longitudinal strain is common in patients with systemic sclerosis and significant
for both ventricles. Global longitudinal strain could become a low-cost, non
invasive and reliable tool in order to detect early cardiac involvement in
systemic sclerosis patients.
PMID- 29966436
TI - A month-by-month analysis of direct oral anticoagulants for secondary prevention
of acute coronary syndrome.
PMID- 29966437
TI - Sigma-2 receptor: past, present and perspectives on multiple therapeutic
exploitations.
AB - Identification of sigma-2 receptor (sig-2R) has been controversial. Nevertheless,
interest in sig-2R is high for its overexpression in tumors and potentials in
oncology. Additionally, sig-2R antagonists inhibit Abeta binding at neurons,
blocking the cognitive impairments of Alzheimer's disease. The most
representative classes of sig-2R ligands are herein treated with focus on
compounds that served to study sig-2R biology and to produce sig-2R: fluorescent
ligands; multifunctional anticancer agents; and targeting nanoparticles. Although
fluorescent ligands serve as 'green' pharmacological tools, sig-2R
multifunctional conjugates and sig-2R-targeted nanoparticles show how sig-2R
targeting increases the activity of anticancer drugs in tumors with reduced
toxicity. Altogether, this review draws a picture of the multiple approaches of
sig-2R ligands in cancer therapy and as Alzheimer's disease modifying disease
agents.
PMID- 29966438
TI - Artificial intelligence in pharmaceutical research and development.
PMID- 29966439
TI - Five-year observation of the relationship between body mass index and glycated
hemoglobin in children with Type 1 diabetes mellitus.
AB - BACKGROUND: Poor metabolic control is a well-recognized risk factor for
cardiovascular disease. However, the relationship between such factor as body
weight and metabolic control in children with diabetes mellitus type 1 (DM1) is
unclear. The aim of this study was to examine the relationships between body
weight, age, metabolic control, sex, and form of insulin therapy in children with
DM1. METHODS: This was a retrospective study of children with DM1 treated at one
diabetes center for a minimum of 5 years since diagnosis. RESULTS: Median body
mass index standard deviation score (BMI-SDS) increased annually (p = .0042) on
average 0.08 +/- 0.27 per year throughout the observation. As well HbA1c and
daily dose insulin increased annually (p < .0001; p < .0001, respectively) on
average by 0.43 +/- 0.79 and by 0.13 +/- 0.17 per year. Percentage of good
metabolic control - HbA1c cut-off of 6.5% - gradually worsened in all patients
over the 5 years, with a higher percentage of girls experiencing poor metabolic
control (84.48% of girls vs. 77.87% of boys; p = .01895). No correlation between
BMI-SDS and metabolic control (HbA1c) was found (R = 0.09, p = .60). CONCLUSIONS:
Body weight appears to be more affected by non-diabetic factors (e.g. irregular
eating and sedentary lifestyle) than by the clinical course of diabetes.
Metabolic control and body weight must be maintained in all children with DM1
(males and females) to reduce their future risk of cardiovascular disease.
PMID- 29966440
TI - Influence of intense training cycle and psychometric status on technical and
physiological aspects performed during the small-sided games in soccer players.
AB - The study investigated the effect of intense training cycle (IT) of early season
preparation period (SPP) and psychological status on technical and physiological
parameters during small-sided games (SSG) and the relationships between these
variables. Sixteen professional soccer players participated in the study (mean+/
SD: age: 24.5+/-4.1). Training load (TL), Total quality recovery (TQR) and well
being indices were performed daily. TL increased progressively (%TL=31.56 [AU]).
Physiological variables did not change after IT and were not influenced by well
being indices and TQR. Technical aspects were negatively altered after IT
(p<0.05). TL was significantly correlated with successful passes (r=-0.57,
p=0.02), interceptions (r=-0.83, p<0.001) and lost balls (r=0.73, p=0.002). Well
being and TQR were related to successful passes, interceptions and lost passes
[(r=-0.55, p=0.03; r=-0.75, p=0.001; r=-0.69, p=0.004); (r=0.54, p=0.03; r=-0.76,
p=0.001; r=-0.69, p=0.004), respectively]. TL, Well-being indices and TQR
represent a useful strategy for coaches to control technical aspects in soccer
players during SPP.
PMID- 29966441
TI - Triptolide antagonized the cisplatin resistance in human ovarian cancer cell line
A2780/CP70 via hsa-mir-6751.
AB - AIM: We aimed to investigate the effect of triptolide on cisplatin resistance in
ovarian cancer cell lines. METHODS: The apoptosis of ovarian cancer cell lines
A2780 and A2780/CP70 was determined by flow cytometry. Protein expression levels
of Hexokinase 2 (HK2) were detected by western blot. Possible mRNAs which target
HK 2 expression were predicted through online tools miRbase. RESULTS: Triptolide
promoted cell apoptosis of cisplatin-resistant ovarian cancer cell line
A2780/CP70. Triptolide treatment sensitized the effect of cisplatin in
A2780/CP70, as evidenced by decreased survival fraction of A2780/CP70 cells.
Mechanically, triptolide treatment inhibited HK 2 expression in A2780/CP70 cells.
In addition, Hsa-mir-6751 expression level was upregulated in A2780/CP70 cells
after triptolide treatment.
PMID- 29966442
TI - Thrombin-Induced Responses via Protease-Activated Receptor 1 Blocked by the
Endothelium on Isolated Porcine Retinal Arterioles.
AB - PURPOSE: Thrombin, a serine protease, causes organ-specific responses to vessels.
However, the mechanism by which thrombin affects the retinal microcirculation
remains unclear. We examined the effects of thrombin on the retinal
microvasculature and signaling mechanisms. METHODS: Porcine retinal arterioles
were isolated, cannulated, and pressurized (55 cmH2O) without flow in this in
vitro study. Videomicroscopy techniques recorded changes in diameter in the
retinal arterioles in response to thrombin at concentrations ranging from 0.001
to 20 mU/ml. RESULTS: Extraluminal administration of thrombin induced
concentration-dependent vascular responses, that is, vasoconstriction at low
concentrations less than 5 mU/ml and vasorelaxation with high concentrations
greater than 5 mU/ml. However, intraluminal administration of thrombin (5 mU/m)
did not constrict the retinal arterioles; in denuded vessels, intraluminal
administration constricted the retinal arterioles. Thrombin-induced
vasoconstriction was significantly (p < 0.01) suppressed by pretreatment with a
protein kinase C (PKC) inhibitor and a protease-activated receptor (PAR)-1
inhibitor but not by PAR-2 and PAR-4 inhibitors or denudation. A rho kinase
(ROCK) inhibitor also suppressed thrombin-induced vasoconstriction (5 mU/ml)
compared with sodium nitroprusside. Endothelial denudation and pretreatment with
an endothelial nitric oxide (NO) synthase inhibitor suppressed vasorelaxation
caused by a high concentration of thrombin. CONCLUSIONS: A low concentration of
thrombin causes vasoconstriction of smooth muscles via PAR-1, PKC, and ROCK, and
a high concentration of thrombin possibly causes vasorelaxation of the retinal
arterioles via nitric oxide synthase activation in the endothelium. The vascular
endothelium might block signaling of thrombin-induced vasoconstriction in the
retinal arterioles when administered intraluminally.
PMID- 29966443
TI - Search for the Source of the Retinal Relaxing Factor.
AB - : Purpose/Aim of the study: the retinal relaxing factor (RRF) is an unidentified
paracrine factor, which is continuously released from retinal tissue and causes
smooth muscle cell relaxation. This study tried to identify the cellular source
of the RRF. Furthermore, the possible RRF release by voltage-dependent sodium
channel activation and the calcium-dependency of the RRF release were
investigated. MATERIALS AND METHODS: mouse femoral arteries were mounted in
myograph baths for in vitro isometric tension measurements. The vasorelaxing
effect of chicken retinas, which contain no vascular cells, and of solutions
incubated with MIO-M1 or primary Muller cell cultures were evaluated. The RRF
release of other retinal cells was investigated by using cell type inhibitors.
Concentration-response curves of veratridine, a voltage-dependent sodium channel
activator, were constructed in the presence or absence of mouse retinal tissue to
evaluate the RRF release. The calcium-dependency of the RRF release was
investigated by evaluating the vasorelaxing effect of RRF-containing solutions
made out of chicken retinas in the absence or presence of calcium. RESULTS:
Chicken retinas induced vasorelaxation, whereas solutions incubated with Muller
cell cultures did not. Moreover, the gliotoxin DL-alpha-aminoadipic acid, the
microglia inhibitor minocycline, and the tetrodotoxin-resistant voltage-dependent
sodium channel 1.8 inhibitor A-803467 could not reduce the RRF-induced
relaxation. Concentration-response curves of veratridine were not enlarged in the
presence of retinal tissue, and RRF-containing solutions made in the absence of
calcium induced a substantial, but reduced vasorelaxation. CONCLUSIONS: the RRF
is not released from vascular cells and probably neither from glial cells. The
retinal cell type that does release the RRF remains unclear. Veratridine does not
stimulate the RRF release in mice, and the RRF release in chickens is calcium
dependent as well as calcium-independent.
PMID- 29966444
TI - Impact of primary tumor side on the outcomes of patients with non-metastatic
colon cancer; a patient-level pooled analysis of two clinical trials.
AB - OBJECTIVE: To assess the impact of primary tumor side on the outcomes of non
metastatic colon cancer patients included in two clinical trials. METHODS:
Overall and disease-free survivals were assessed according to the side of the
tumor, through Kaplan-Meier analysis. Univariate and Multivariate analysis of
predictors of disease-free survival was performed through Cox regression
analysis. RESULTS: Kaplan-Meier analysis of disease-free survival according to
the side of the primary tumor was conducted. In the overall cohort, the right
sided disease has longer disease-free survival compared to left-sided disease (p
= 0.005). When the analysis was repeated among different treatment strata
(observation, adjuvant 5FU/LCV, adjuvant edrecolomab), right-sided colon cancer
has longer disease-free survival among observation-treated patients only (p =
0.020). Multivariate analysis was conducted among the three subsets of adjuvant
treatment. The left side of the primary tumor was predictive of worse disease
free survival in patients treated with observation only (p = 0.005) but not in
patients treated with adjuvant 5FU/LCV (p = 0.345) or patients treated with
adjuvant edrecolomab (p = 0.661). CONCLUSION: Stage II right-sided colon cancer
patients have better disease-free survival compared to stage II left-sided colon
cancer patients when treated with surgery only. This survival difference
disappears if patients were treated with adjuvant fluoropyrimidines.
PMID- 29966445
TI - Persistent mixed cryoglobulinemia after successful antiviral treatment of chronic
hepatitis C virus infection: What's the next?
PMID- 29966446
TI - The use of single balloon enteroscopy in Crohn's disease and its impact on
clinical outcome.
AB - OBJECTIVES: Single balloon enteroscopy (SBE) is an effective and safe modality
for the diagnosis and therapeutic intervention of small bowel disorders. Its use
in patients with Crohn's disease (CD) and particularly its effect on management
changes in CD have not yet been determined. MATERIALS AND METHODS: We performed a
retrospective review of the endoscopic and clinical data available on a cohort of
patients with small bowel CD who had undergone SBE to determine the diagnostic
and therapeutic yield of the procedure and the initial and longer-term impact it
had on clinical management. RESULTS: About 52 patients have undergone SBE in our
unit for the investigation of known (n = 39) or suspected (n = 13) small bowel CD
with a diagnostic yield of 77% and 39%, respectively. SBE had an immediate
clinical impact in 69% (n = 33) of patients, including dilatation of a stricture
in 27% (n = 13), initiation or adjustment of dose of medications in 48% (n = 23),
referral for surgical resection in 6% (n = 3). Moreover, the procedure permitted
determining a new diagnosis of CD in 8% of the patients (n = 4), and excluding it
in 8% (n = 4). Longer term follow-up was available in 34 patients (65%) which
showed a significant difference in mean HBI score from 6.6 before the procedure
to 4.2 after it (p < .0001). CONCLUSIONS: SBE has a high diagnostic and
therapeutic yield in CD and significantly impacts disease management. Careful
patient selection is a key factor in optimizing its use in CD.
PMID- 29966447
TI - Adaptive mining and model building of medicinal chemistry data with a multi
metric perspective.
PMID- 29966448
TI - Platycosides P and Q, two new triterpene saponins from Platycodon grandiflorum.
AB - The EtOH extract of the roots of Platycodon grandiflorum afforded two new
triterpene saponins platycoside P (1) and platycoside Q (2). Their structures
were elucidated based on spectroscopic means and hydrolysis products. These
compounds were evaluated for inhibitory activity against LPS-induced TNF-alpha
production in RAW 246.7 macrophages. Compounds 1 and 2 showed inhibitory activity
with the inhibition ratios (%) of 38.6 and 44.1 at 50 MUM, respectively.
PMID- 29966449
TI - 2H-Pyranone and isocoumarin derivatives isolated from the plant pathogenic fungus
Leptosphaena maculans.
AB - Two new 2H-pyranones and two new isocoumarin derivatives, maculanslines A-D (1
4), together with seven known compounds (5-11), were isolated from the plant
pathogenic fungus Leptosphaena maculans. Their planar structures and absolute
configuration were elucidated by comprehensive spectroscopic techniques including
high-resolution electrospray ionization mass spectrum, 1D and 2D nuclear magnetic
resonance, as well as electronic circular dichroism. All 11 compounds were tested
for their inhibitory activity against alpha-glucosidase. Compound 1 showed
moderate inhibitory activity against alpha-glucosidase with IC50 of 74.35 MUM.
PMID- 29966450
TI - A Cross-Sectional Observational Study of Nailfold Capillary Morphology in
Uveitis.
AB - PURPOSE: We performed nailfold capillary microscopy to explore microvasculature
abnormalities in uveitis overall and uveitis stratified in various ways. METHODS:
This was a cross-sectional, case-control, observational study. One hundred and
seven uveitis patients and 130 control subjects were included. We used a JH-1004
capillaroscope to perform nailfold capillary video microscopy on the fourth and
fifth digits of each subject's nondominant hand. Videos were evaluated for
hemorrhages, dilated capillary loops > 25 um, and avascular zones > 200 um.
Univariate analyses were used for the assessment of case-control morphological
differences and multivariate analyses were performed to assess the relation
between nailfold capillaroscopic findings and uveitis subgroups. RESULTS: In
univariate analysis, uveitis patients were more likely to have higher tortuosity
ratings and reduced capillary density compared to controls (p < 0.001 for both);
furthermore, dilated capillary loops, avascular zone and hemorrhages were more
frequent in uveitis versus control subjects (p < 0.001 for all). Among cases,
every unit increase in capillary density (vessels/mm) was associated with active
uveitis (n = 72 cases) versus inactive disease (n = 35 cases; odds ratio (OR) =
1.7; (95% confidence interval (CI), 1.2-2.5) in multivariate analysis.
Furthermore, the presence of any nailfold hemorrhage versus the absence of
hemorrhage was more likely to be associated with posterior and panuveitis (n = 41
cases combined) compared to anterior and intermediate uveitis (n = 66 cases
combined; OR = 5.8; 95% CI, 2.3-14.2). Moreover, we found a positive correlation
between peripheral retinal leakage and nailfold capillaries dilation (r = 0.33; p
= 0.015) that was not strictly significant based on the number of comparisons
made. CONCLUSIONS: Our study provides support for non-ocular capillary bed
abnormalities in uveitis, with interesting correlations based on disease stage
and anatomical classification.
PMID- 29966451
TI - Elimination of Signaling by the Luteinizing Hormone Receptor Reduces Ocular VEGF
and Retinal Vascularization during Mouse Eye Development.
AB - : Purpose/Aim: Vascular endothelial growth factor (VEGF) dysregulation is
implicated in the pathogenesis of retinopathy of prematurity (ROP). Identifying
the factors that contribute to VEGF regulation during normal retinal
vascularization is the key to ROP prevention. Currently, physiologic hypoxia is
thought to be responsible for retinal VEGF regulation in utero. However, a
potential hormonal contribution to VEGF regulation during eye development has not
been fully investigated. The placental hormone, human chorionic gonadotropin and
the pituitary hormone, and luteinizing hormone (LH) induce VEGF expression in
several tissue types. Both of these gonadotropins activate the same LH receptor
(LHR) in the human body; LHRs are expressed in the retina. In this study, we
aimed to show that LHR signaling participates in VEGF regulation in the
developing eye. METHODS: When offspring from breeding pairs of LHR knockout mice
(lhrkos) reached 21 days old, eyes and serum were extracted from homozygote
lhrkos and wildtype (WT) siblings. VEGF levels were measured using Mouse VEGF
Quantikine immunoassay kit. Retinas were incubated with isolectin for endothelial
cell staining, flat mounted and imaged by confocal microscopy. Retinal vascular
density was quantified using Imaris software. Some eyes were sectioned and
stained for histopathologic review. RESULTS: Ocular VEGF and retinal vascular
volumes were significantly reduced by ~ 15% in lhrko eyes. Serum VEGF was not
changed. The lhrko retinas did not display any anomalies. CONCLUSIONS: We provide
evidence that LHR signaling plays a role in VEGF regulation and vascularization
in the developing eye. Given that human preterm infants may have altered LHR
activity, the effect of gonadotropins on eye development should be further
studied to identify novel strategies for ROP prevention.
PMID- 29966452
TI - Design of selective histone deacetylase inhibitors: rethinking classical
pharmacophore.
AB - For two decades, a classical pharmacophore model comprising a zinc binding group,
a linker and a cap group, has been used for the development of histone
deacetylase (HDAC) inhibitors. However, some of the recently reported selective
HDAC inhibitors targeting additional, usually subtype specific, cavities in the
binding pocket show supplementary features which do not fit this classical
pharmacophore. We, therefore, propose an extended pharmacophore model, which can
describe almost all currently known HDAC inhibitors. This pharmacophore consists
of six pharmacophoric features and should be helpful for the classification and
design of selective HDAC inhibitors.
PMID- 29966453
TI - Data analytics and deep learning in medicinal chemistry.
PMID- 29966454
TI - Corrigendum.
PMID- 29966455
TI - Corrigendum.
PMID- 29966456
TI - Managing myeloma with limited resources in the era of novel drugs.
PMID- 29966457
TI - Development of the Social Participation Restrictions Questionnaire (SPaRQ)
through consultation with adults with hearing loss, researchers, and clinicians:
a content evaluation study.
AB - OBJECTIVE: This research aimed to evaluate the content of the Social
Participation Restrictions Questionnaire (SPaRQ) in terms of its relevance,
clarity, comprehensiveness, acceptability to adults with hearing loss, and
responsiveness. DESIGN: Cognitive interviews and a subject matter expert survey
were conducted. The interview data were analysed using thematic analysis and a
taxonomy of questionnaire clarity problems. Descriptive statistics were
calculated for the survey data. STUDY SAMPLE: Fourteen adults with hearing loss
participated in the cognitive interviews. Twenty clinicians and academics
completed the subject matter expert survey. RESULTS: The majority of the SPaRQ
content was found to be relevant, clear, comprehensive, and acceptable. However,
an important clarity problem was identified: many adults with hearing loss
struggled to switch from answering positively worded items (e.g. "I can attend
social gatherings") to answering negatively-worded items (e.g. "I feel
isolated"). Several subject matter experts found responsiveness difficult to
assess. The SPaRQ was amended where necessary. CONCLUSION: Few hearing-specific
questionnaires have undergone content evaluation. This study highlights the value
of content evaluation as a means of identifying important flaws and improving the
quality of a measure. The next stage of this research is a psychometric
evaluation of the measure.
PMID- 29966458
TI - Daunorubicin during delayed intensification decreases the incidence of infectious
complications - a randomized comparison in trial CoALL 08-09.
AB - Anthracyclines are integral components of antileukemic treatment. Apart from
cardiotoxicity, myelosuppression and infectious complications have been described
for doxorubicin (DOX) and daunorubicin (DNR) as predominant side effects, but
little is known about their differential toxicities. To address the question
whether DNR is associated with a lower rate of infectious complications compared
with DOX, 307 children with newly diagnosed acute lymphoblastic leukemia,
enrolled in trial CoALL 08-09, were randomized to receive either DOX 30 mg/m2 (n
= 153) or DNR 36 mg/m2 (n = 154) in delayed intensification. Hematologic
toxicities and stomatitis were less frequent in the DNR group resulting in a
significantly lower rate of infections in the DNR arm (27% vs. 59%, p < .0001).
Survival was equal in both arms (95% SE 2%) (p = .55), with an insignificant
difference in the relapse rate (RR 0.12 (SE = 0.03) in the DOX arm vs. 0.16 (SE =
0.04) in the DNR arm; p = .37; Hazard ratio 1.3; 95% confidence interval 0.7
2.6). In conclusion, DNR given in delayed intensification is associated with a
lower incidence of infectious complications without loss of efficacy.
PMID- 29966459
TI - Marijuana matters: reviewing the impact of marijuana on cognition, brain
structure and function, & exploring policy implications and barriers to research.
AB - The neurobiologic effects of cannabis, commonly referred to as 'marijuana' (MJ),
have been studied for decades. The impact of recreational MJ use on cognition and
measures of brain function and structure is outlined, and variables influencing
study results are discussed, including age of the consumer, patterns of MJ use,
variations in MJ potency, and the presence of additional cannabinoids. Although
evidence suggests that chronic, heavy recreational MJ use is related to cognitive
decrements and neural changes, particularly when use begins in adolescence,
findings from studies of recreational MJ users may not be applicable to medical
marijuana (MMJ) patients given differences in demographic variables, product
selection, and reasons for use. Although additional research is needed to fully
understand the impact of MJ and individual cannabinoids on the brain, current
findings are beginning to inform public policy, including considerations for age
limits, potential limits for some cannabinoids, and guidelines for use. However,
barriers continue to impede researchers' ability to conduct studies that will
guide policy change and provide vital information to consumers and patients
regarding best practices and safest methods for use. The need for information is
critical, as legalization of MJ for medical and recreational use is increasingly
widespread.
PMID- 29966460
TI - Arterial calcium stimulation with hepatic venous sampling predicts the
localization and size of the insulinoma as well as postoperative weight loss.
PMID- 29966461
TI - Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma
following CAR T-cell therapy.
PMID- 29966462
TI - Elevated markers of brain injury as a result of clinically asymptomatic high
acceleration head impacts in high-school football athletes.
AB - OBJECTIVE This prospective observational cohort study of high-school football
athletes was performed to determine if high-acceleration head impacts (HHIs) that
do not result in clinically diagnosed concussion still lead to increases in serum
levels of biomarkers indicating traumatic brain injury (TBI) in asymptomatic
athletes and to determine the longitudinal profile of these biomarkers over the
course of the football season. METHODS Sixteen varsity high-school football
athletes underwent baseline neurocognitive testing and blood sampling for the
biomarkers tau, ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light
protein (NF-L), glial fibrillary acidic protein (GFAP), and spectrin breakdown
products (SBDPs). All athletes wore helmet-based accelerometers to measure and
record head impact data during all practices and games. At various time points
during the season, 6 of these athletes met the criteria for HHI (linear
acceleration > 95 g and rotational acceleration > 3760 rad/sec 2 ); in these
athletes a second blood sample was drawn at the end of the athletic event during
which the HHI occurred. Five athletes who did not meet the criteria for HHI
underwent repeat blood sampling following the final game of the season. In a
separate analysis, all athletes who did not receive a diagnosis of concussion
during the season (n = 12) underwent repeat neurocognitive testing and blood
sampling after the end of the season. RESULTS Total tau levels increased 492.6%
+/- 109.8% from baseline to postsession values in athletes who received an HHI,
compared with 164% +/- 35% in athletes who did not receive an HHI (p = 0.03).
Similarly, UCH-L1 levels increased 738.2% +/- 163.3% in athletes following an
HHI, compared with 237.7% +/- 71.9% in athletes in whom there was no HHI (p =
0.03). At the end of the season, researchers found that tau levels had increased
0.6 +/- 0.2 pg/ml (p = 0.003) and UCH-L1 levels had increased 144.3 +/- 56 pg/ml
(p = 0.002). No significant elevations in serum NF-L, GFAP, or SBDPs were seen
between baseline and end-of-athletic event or end-of-season sampling (for all, p
> 0.05). CONCLUSIONS In this pilot study on asymptomatic football athletes, an
HHI was associated with increased markers of neuronal (UCH-L1) and axonal (tau)
injury when compared with values in control athletes. These same markers were
also increased in nonconcussed athletes following the football season.
PMID- 29966463
TI - Significance of treatment response when managing patients with primary central
nervous system lymphoma.
AB - The precise role of radiation therapy in primary central nervous system lymphoma
(PCNSL) remains controversial. We reviewed the records of all patients treated
for PCNSL at our center between 2004 and 2015. A total of 103 patients treated
with either chemotherapy alone (n = 30), radiotherapy alone (n = 36), or combined
modality treatment (n = 37) were analyzed. The median progression-free survival
(PFS) and overall survival (OS) were 13.9 and 20.9 months, respectively. Of those
who received chemotherapy, 52.2% achieved complete response/ unconfirmed complete
response (CR/Cru) after induction; a trend for improved PFS was observed for
those who received consolidation WBRT (NR vs. 30.1 months, p = .092) but not OS
(NR vs. 31.6 months, p = .283). Patients who achieved a partial response with
chemotherapy and proceeded with WBRT had a similar long-term survival to those
who achieved CR/CRu with chemotherapy without WBRT (PFS 15.2 vs. 30.1 months, p =
.888; OS 22.0 vs. 31.6 months, p = .340). Consolidation WBRT improved PFS, but
not OS, and this must be balanced against possible risks of neurotoxicity.
PMID- 29966464
TI - Post-transplant lymphoproliferative disorders after solid organ and hematopoietic
stem cell transplantation.
AB - Post-transplant lymphoproliferative disorders (PTLD) are a rare complication
after both solid organ (SOT) and allogeneic hematopoietic stem cell
transplantation (allo-HSCT). In this single center retrospective study, we
compared clinical, biological, and histological features, and outcomes of PTLD
after both types of transplant. We identified 82 PTLD (61 after SOT and 21 after
allo-HSCT). The presence of B symptoms, Waldeyer ring, spleen, central nervous
system, and liver involvement, and advanced Ann-Arbor stage were more frequent in
allo-HSCT recipients. PTLD had an earlier onset in allo-HSCT than in SOT cohort
(4 vs. 64 months, p < .0001). PTLD was EBV-positive in 100% of allo-HSCT, in
contrast to 47% of SOT (p = .0002). Four years after PTLD diagnosis, median
overall survival was 32% (95% CI, 22-48) and 10% (95% CI, 2-49) in SOT and allo
HSCT recipients, respectively (p = .002). In conclusion, the clinical
presentation and the outcome of PTLD varies greatly depending on the type of
transplant.
PMID- 29966465
TI - Autologous transplantation improves survival rates for follicular lymphoma
patients who relapse within two years of chemoimmunotherapy: a multi-center
retrospective analysis of consecutively treated patients in the real world.
AB - Although chemoimmunotherapy improves outcomes for patients with follicular
lymphoma (FL), approximately 20% of patients experience early disease progression
within two years of treatment and subsequently poor median survival. We conducted
a retrospective study to evaluate survival rates of patients with early relapse
who were treated with or without autologous transplantation. Of 517 patients with
FL and who received chemoimmunotherapy, 152 relapsed and survived a minimum of
four months after progression, including 84 (55.3%) with early relapse <=2 years
following initial therapy and 68 (44.7%) with later relapse. Five-year survival
was superior for patients who received autologous transplantation compared to non
transplanted patients within the early relapse group (85.4% vs 57.9%, p = .001),
but not within the late relapse group (p = .64). Given the limitations of a
retrospective study, our study may suggest that the use of autologous
transplantation for FL patients who relapse within two years of initial
chemoimmunotherapy is associated with improved survival.
PMID- 29966466
TI - An Iceberg Phenomenon in Dementia: Pain.
AB - BACKGROUND: Pain is one of the most frequent symptoms in older adults. It
severely impairs quality of life, increases delirium risk, and may lead to
progression of dementia. Assessment of pain performed by taking anamnesis from
the patient is not reliable in patients with dementia due to cooperation and
communication problems. The aim of this study was to assess pain and its
consequences in patients with dementia. METHODS: Seventy-five nursing home
residents with dementia were enrolled. After comprehensive geriatric assessment,
presence of pain was asked to patients, and Pain Assessment in Advanced Dementia
(PAINAD), Discomfort Scale for Dementia of the Alzheimer's Type (DS-DAT), Pain
Assessment for the Dementing Elderly (PADE), Wong-Baker Faces Pain Rating Scale,
and Numeric Rating Scale tests were performed. RESULTS: Mean age was 81.1 (7.0),
and 46.7% (n = 35) were female. Thirty-two percent of the patients were at early
stage, 24% at moderate stage, and 44% at severe stage. Although the number of
patients declaring pain was lower in moderate and severe stage, scores of PADE,
PAINAD, and DS-DAT were significantly higher in severe stage showing the presence
of pain ( P < .001). Furthermore, scores of PADE, PAINAD, and DS-DAT were
negatively correlated with comprehensive geriatric assessment test scores.
CONCLUSION: These results demonstrate that pain is not rare in patients with
dementia, but they are not usually capable of expressing it, especially in the
severe stage. Therefore, objective pain assessment scales developed for patients
with dementia should be routinely used and management of pain should be done
regarding the association of pain with other geriatric syndromes.
PMID- 29966467
TI - Radiation therapy in primary testicular lymphoma: does practice match the
standard of care?
PMID- 29966468
TI - Bone marrow-derived mesenchymal stem/stromal cells from patients with splenic
marginal zone lymphoma are intrinsically impaired and influence the malignant B
cells.
PMID- 29966469
TI - Atg9 proteins, not so different after all.
AB - Macroautophagy (hereafter autophagy) is a catabolic pathway present in all
eukaryotic cells. The yeast Saccharomyces cerevisiae has been pivotal in the
identification and characterization of the key autophagy-related (Atg) proteins,
which play a central role in the generation of autophagosomes. The components of
the core Atg/ATG machinery and their functions are highly conserved among
species, although mammalian cells also have isoforms and auxiliary factors.
Atg9/ATG9 is the only transmembrane protein that is part of the core Atg/ATG
machinery, but it appears to have divergent localizations and molecular roles in
yeast and mammals. A recent experimental analysis of the yeast endo-lysosomal
system by the laboratory of Benjamin Glick, however, suggests a more simple
organization of this membrane system. Although this study has not examined yeast
Atg9, its findings place this protein in the same compartments as its mammalian
counterpart. Here, we will discuss the implications of this conceptual change on
the trafficking of yeast Atg9 and its function in autophagy.
PMID- 29966470
TI - Deletion of CDKN2A/B is associated with inferior relapse free survival in
pediatric B cell acute lymphoblastic leukemia.
AB - Considering conflicting data on CDKN2A/B deletion in ALL, this study to assess
its prognostic significance as an independent marker in a total of 96 pediatric B
and T-ALL cases was planned. The overall frequency of CDKN2A/B deletion was 44%
(n = 43) with 36% (30/83) in B-ALL and 100% (13/13) in T-ALL. CDKN2A/B deletion
was significantly associated with high WBC count (p = .002) and National Cancer
Institute risk (p = .01) in B-ALL. Importantly, CDKN2A/B deletion cases had poor
EFS of 42% at 28 months compared to EFS of 90% in rest (p = .0004). Further,
relapse free survival was only 56% for cases with CDKN2A/B deletions (n = 25),
compared to 100% in control group (p = .001). Moreover, CDKN2A/B deletion was the
only risk factor associated with early relapse (p = .01) compared to IKZF1
deletion (p = .73) or occurrence of BCR-ABL1 fusion transcript (p = .26). Thus
our study data highlights potential prognostic role of CDKN2A/B deletions in
early disease stratification in pediatric B-ALL.
PMID- 29966471
TI - Renal complications of primary myelofibrosis.
PMID- 29966472
TI - First fully automated planning solution for robotic radiosurgery - comparison
with automatically planned volumetric arc therapy for prostate cancer.
AB - BACKGROUND: For conventional radiotherapy treatment units, automated planning can
significantly improve plan quality. For robotic radiosurgery, systems for
automatic generation of clinically deliverable plans do not yet exist. For
prostate stereotactic body radiation therapy (SBRT), few studies have
systematically compared VMAT with robotic treatment. MATERIAL AND METHODS: The
multi-criteria autoplanning optimizer, developed at our institute, was coupled to
the commercial treatment planning system of our robotic treatment unit, for fully
automated generation of clinically deliverable plans (autoROBOT). The system was
then validated by comparing autoROBOT plans with manually generated plans. Next,
the autoROBOT system was used for systematic comparisons between autoROBOT plans
and VMAT plans, that were also automatically generated (autoVMAT). CTV-PTV
margins of 3 mm were used for autoROBOT (clinical routine) and autoVMAT plan
generation. For autoVMAT, an extra plan was generated with 5 mm margin (often
applied for VMAT). Plans were generated for a 4 * 9.5 Gy fractionation scheme.
RESULTS: Compared to manual planning, autoROBOT improved rectum D[Formula: see
text] (16%), V[Formula: see text] (75%) and D[Formula: see text] (41%), and
bladder D[Formula: see text] (37%) (all p [Formula: see text] .002), with equal
PTV coverage. In the autoROBOT and autoVMAT comparison, both with 3 mm margin,
rectum doses were lower for autoROBOT by 5% for rectum D[Formula: see text]
(p=.002), 33% for V[Formula: see text] (p=.001) and 4% for D[Formula: see text]
(p=.05), with comparable PTV coverage and other OAR sparing. With 5 mm margin for
VMAT, 18/20 plans had a PTV coverage lower than requested (<95%) and all plans
had higher rectum doses than autoROBOT (mean percentage differences of 13% for
D[Formula: see text], 69% for V[Formula: see text] and 32% for D[Formula: see
text] (all p<.001)). CONCLUSIONS: The first system for fully automated generation
of clinically deliverable robotic plans was built. Autoplanning did largely
enhance robotic plan quality, compared to manual planning. Using autoplanning for
both the robotic system and VMAT, superiority of non-coplanar robotic treatment
compared to coplanar VMAT for prostate SBRT was demonstrated.
PMID- 29966473
TI - Metabolic behavior and prognostic value of early and end of treatment 18F-FDG
PET/CT in adult Burkitt's lymphoma: the role of Deauville and IHP criteria.
AB - Burkitt's lymphoma is a lymphoma with unclear metabolic behavior at 18F-FDG
PET/CT and no validated criteria in treatment evaluation and prediction of
outcome exist. Sixty-five patients were retrospectively included: all underwent
baseline 18F-FDG-PET/CT, 56 interim PET/CT (iPET/CT) and 54 end of treatment
PET/CT (eotPET/CT) after chemotherapy. Interim and eotPET/CT results were
visually interpreted according to the criteria of the IHP and Deauville-five
point-scale. Results were correlated with PFS and OS to assess and to compare the
predictive value of iPET and eotPET according to each criterion. All baseline
PET/CT showed increased 18F-FDG uptake in nodal and extranodal lesions. The
median PFS and OS were 44.6 and 48.2 months with 3-year and 5-year PFS of 76% and
62% and 3-year and 5-year OS of 71% and 57%, respectively. EotPET/CT results
using DC and IHP significantly correlate with OS and PFS; while iPET/CT did not
correlated with OS and PFS.
PMID- 29966474
TI - Hemophagocytic lymphohistiocytosis in adults.
AB - Hemophagocytic lymphohistiocytosis (HLH), a rare but life-threatening condition
characterized by uncontrolled inflammation, is increasingly recognized in adults.
The management of adult onset HLH is challenging, in part due to gaps in current
state of knowledge on etiology, clinical presentation, diagnosis, and management.
HLH secondary to triggers such as infections, autoimmune disorders, and
malignancy are more commonly seen in adults although cases of familial form have
also been reported. Underlying conditions such as sepsis, or malignancy could
pose as major confounders while applying universal diagnostic criteria, and
therefore could lead to delay in diagnosis. Despite advent of newer therapeutic
agents, outcomes of adults continue to remain poor. Future efforts need to be
orchestrated to develop evidence-based tailored therapies to improve outcomes of
this under recognized heterogeneous entity.
PMID- 29966475
TI - Additional benefits of telomere length (TL) measurements in chronic lymphocytic
leukemia.
PMID- 29966476
TI - Impact of oil recession on community mental health service utilization in an oil
sands mining region in Canada.
AB - OBJECTIVES: This retrospective clinical audit compared changes in community
mental health service utilization before and during an economic recession in an
oil sands region in Canada which was characterized by a doubling of unemployment
rates and poor economic outlook. METHODS: Sociodemographic descriptors,
psychiatric antecedents, clinical characteristics and follow-up care were
compared before and during the recession for newly assessed patients in community
mental health clinics located across a Northern Alberta oil mining region. Data
were collected retrospectively as part of a clinical audit process and then
analysed with descriptive statistics, cross-tabular univariate analyses with chi
square tests using SPSS version 20. RESULTS: A total of 1,465 patients were
included. Sociodemographic factors disproportionately elevated during the
recession included male sex, Caucasian ethnicity, own home ownership, higher
levels of education and unemployment. More patients seeking mental health care
were already taking psychotropic medications (e.g. antipsychotics,
benzodiazepines and stimulants). At the same time, disproportionately fewer
patients engaged in substance abuse or had a prior formal history of mental
health problems. The referral reasons during recession were less likely to be
associated with substance abuse or mood concerns and more likely for 'other'
reasons. The patients seeking psychiatric help during a recession were
disproportionately likely to be diagnosed with personality disorders and 'other'
less common diagnostic categories and less likely to suffer from mood or trauma
related diagnoses. Referrals for counselling and social services were also
disproportionately more common during the recession. CONCLUSION: This study
provides a comprehensive description of longitudinal patterns of mental health
service utilization before and during a recession. The findings provide important
evidence for policy and planning decisions to encourage resource allocation to
help promote accessibility of the most needed community mental health resources.
PMID- 29966478
TI - A renaissance for autologous transplantation in follicular lymphoma?
PMID- 29966477
TI - Neuropsychiatric Symptoms and Caregiver Burden in Individuals With Alzheimer's
Disease: The TEAM-AD VA Cooperative Study.
AB - OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms (NPS) in mild
to-moderate Alzheimer disease (AD) and their association with caregiver burden.
METHODS: Secondary analyses of baseline data from the Trial of Vitamin E and
Memantine in Alzheimer's Disease (TEAM-AD) (N=613). Neuropsychiatric Inventory
were used to measure severity of NPS and caregiver activity survey to measure
caregiver burden. RESULTS: A total of 87% of patients displayed at least 1 NPS;
70% displayed clinically meaningful NPS. The most common symptoms were apathy
(47%), irritability (44%), agitation (42%), and depression (40%). Those with
moderate AD had more severe NPS than those with mild AD ( P = .03).
Neuropsychiatric symptoms were significantly associated with caregiver time after
adjusting for age, education, cognitive function, and comorbidity ( P-value <
.0001) with every point increase in NPS associated with a 10-minute increase in
caregiver time. CONCLUSION: Neuropsychiatric symptoms were prevalent in both mild
and moderate AD, even in patients receiving treatment with an
acetylcholinesterase inhibitors, and were more severe in moderate AD and
associated with greater caregiver time.
PMID- 29966479
TI - Congestive heart failure among children with acute leukemia: a population-based
matched cohort study.
AB - The purpose was to describe the incidence and risk factors of congestive heart
failure (CHF) among children with acute lymphoblastic leukemia (ALL) and acute
myeloid leukemia (AML). We included 2053 children (<=18 years) with first primary
ALL and AML diagnosed 1992-2010 and registered in the Pediatric Oncology Group of
Ontario Networked Information System. We identified CHF events through linked
administrative databases. At 10 years, the cumulative incidence of CHF was 1.7%
in ALL and 7.5% in AML. Factors associated with CHF in ALL were female gender,
age <1 year at cancer diagnosis, irradiation and cumulative anthracycline dose
>=250 mg/m2. Irradiation was the only risk factor in AML patients. Of the 23
patients with CHF during active therapy, one developed CHF following treatment
completion. Incidence of CHF were 1.7% in ALL and 7.5% in AML. Most with CHF
during active therapy did not develop CHF after treatment completion.
PMID- 29966481
TI - Godina revisited: a systematic review of traumatic lower extremity wound
reconstruction timing.
AB - : Backround: Marko Godina suggested in 1986 that soft tissue coverage of
traumatic extremity wounds within 72 h of injury optimizes outcomes. Decades
later, these recommendations remain controversial. METHODS: We performed
systematic review of the literature using keywords 'free flap coverage' OR 'soft
tissue reconstruction' AND 'lower extremity trauma' OR 'tibial or fibular
fractures'. Patients receiving free flap or local muscle or fascia flaps were
included. Patients were divided into two groups, one receiving coverage within 72
h of injury (<72 h) and one after 72 h (>72 h). Primary outcome measures were
partial and total flap loss, as well as infection. Use of negative pressure wound
therapy (NPWT) was noted. Descriptive statistics were performed. RESULTS: Twenty
one publications from 1986 to 2015 were included. The <72 h group had 295
patients and the >72 h group 972 patient. Total flap failure rate was 1.4% if
coverage was performed <72 h after injury and 8.8% if >72 h after injury. Partial
flap failure rate was 0.4% if coverage was performed <72 h after injury and 1.8%
if >72 h after injury. Infection rate was 7.7% if coverage was performed <72 h
after injury and 11.6% if >72 h after injury. Among the 182 patients in the >72 h
group receiving NPWT, total flap failure rate was 3.6% and total infection rate
7.3%. CONCLUSIONS: Total and partial flap loss rates, as well as infection rates,
were lower when coverage was performed within 72 h of injury. Supporting Godina's
recommendation, early soft tissue coverage may be beneficial when circumstances
permit. NPWT may be useful when reconstruction is not feasible within 72 h.
PMID- 29966480
TI - Nonmedical Use of Prescription Stimulants Among US High School Students to Help
Study: Results From a National Survey.
AB - OBJECTIVE: Mixed findings exist regarding extent and efficacy of nonmedical use
of prescription stimulants (NMUPS) for study enhancement (SE). This national
study of US high school seniors examined NMUPS for SE and addressed risk/benefit
questions: To what extent are students reporting NMUPS specifically for SE, and
do these individuals demonstrate fewer problem behaviors and superior academic
performance? METHOD: Total of 15 098 US students surveyed (2009-2015) and divided
into 4 subgroups: (1) no past-year NMUPS (nonusers), (2) past-year NMUPS to help
study (NMUPS-SE only), (3) past-year NMUPS for study/nonstudy motives (NMUPS-SE+
other), and (4) past-year NMUPS for nonstudy motives (NMUPS-nonSE only). Student
characteristics (eg, grade point average [GPA]) and substance-related problems
(eg, binge drinking) compared between subgroups. RESULTS: Among students who
reported past-year NMUPS (n = 781), 7.4% reported NMUPS-SE only, 40.9% NMUPS-SE+
other, and 51.7% NMUPS-nonSE only. Odds of binge drinking, cigarette smoking,
marijuana, and opioid nonmedical use significantly higher among all NMUPS
subgroups. GPAs significantly lower among subgroups reporting NMUPS nonstudy
motives; did not differ between NMUPS-SE only and nonusers. CONCLUSIONS: 7% of US
high school seniors engaged in NMUPS for SE only (0.4% total population).
Findings indicate greater substance-related problems without superior academic
performance among NMUPS-SE subgroups.
PMID- 29966482
TI - Harm-benefit analysis - what is the added value? A review of alternative
strategies for weighing harms and benefits as part of the assessment of animal
research.
AB - Animal experiments are widely required to comply with the 3Rs, to minimise harm
to the animals and to serve certain purposes in order to be ethically acceptable.
Recently, however, there has been a drift towards adding a so-called harm-benefit
analysis as an additional requirement in assessing experiments. According to
this, an experiment should only be allowed if there is a positive balance when
the expected harm is weighed against the expected benefits. This paper aims to
assess the added value of this requirement. Two models, the discourse model and
the metric model, are presented. According to the former, the weighing of harms
and benefits must be conducted by a committee in which different stakeholders
engage in a dialogue. Research into how this works in practice, however, shows
that in the absence of an explicit and clearly defined methodology, there are
issues about transparency, consistency and fairness. According to the metric
model, on the other hand, several dimensions of harms and benefits are defined
beforehand and integrated in an explicit weighing scheme. This model, however,
has the problem that it makes no real room for ethical deliberation of the sort
committees undertake, and it has therefore been criticised for being too
technocratic. Also, it is unclear who is to be held accountable for built-in
ethical assumptions. Ultimately, we argue that the two models are not mutually
exclusive and may be combined to make the most of their advantages while reducing
the disadvantages of how harm-benefit analysis in typically undertaken.
PMID- 29966483
TI - Spontaneous Labyrinthine Hemorrhage: A Case Series.
AB - OBJECTIVES: To describe patient characteristics, audiometric outcomes, and
magnetic resonance imaging (MRI) signal patterns in patients with suspected
labyrinthine hemorrhage. STUDY DESIGN: Retrospective review. SETTING: Tertiary
medical center. SUBJECTS AND METHODS: Radiology database was queried for terms
related to labyrinth hemorrhage or labyrinthitis and then selected for patients
in which labyrinthine hemorrhage was suspected in the report. Eleven patients
were identified and all treated at our institution. Blinded assessment of
temporal bone MRI by 2 experienced neuroradiologists was performed and interrater
reliability assessed. Patient demographics, medical comorbidities, and
audiometric outcomes are described. RESULTS: Of the 11 patients identified, the
median patient age was 60 years; 7 were female and 4 male. Ten of 11 patients
presented with unilateral sudden sensorineural hearing loss (SNHL), and 8 of 11
had associated vertigo. One patient experienced vertigo without hearing loss. Of
those presenting with sudden SNHL, 82% were left with nonserviceable American
Academy of Otolaryngology-Head and Neck Surgery class D hearing. Interrater
reliability for detecting T1 signal abnormalities was moderate but very good for
detecting fluid attenuation inversion recovery (FLAIR) signal abnormalities. Most
patients had existing hypertension. Average follow-up was 13.3 months.
CONCLUSION: We present the largest cohort of patients with radiographic diagnosis
of labyrinthine hemorrhage using T1 and FLAIR signal abnormalities on MRI. Most
patients presented with a profound unilateral sudden SNHL that did not recover.
Our findings are consistent with prior reports that abnormal FLAIR signal on MRI
is a reliable marker for detecting inner ear injury and can potentially be used
as a marker for poor prognosis.
PMID- 29966484
TI - Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis
in the social amoeba Dictyostelium discoideum.
AB - Micro (mi)RNAs regulate gene expression in many eukaryotic organisms where they
control diverse biological processes. Their biogenesis, from primary transcripts
to mature miRNAs, have been extensively characterized in animals and plants,
showing distinct differences between these phylogenetically distant groups of
organisms. However, comparably little is known about miRNA biogenesis in
organisms whose evolutionary position is placed in between plants and animals
and/or in unicellular organisms. Here, we investigate miRNA maturation in the
unicellular amoeba Dictyostelium discoideum, belonging to Amoebozoa, which
branched out after plants but before animals. High-throughput sequencing of small
RNAs and poly(A)-selected RNAs demonstrated that the Dicer-like protein DrnB is
required, and essentially specific, for global miRNA maturation in D. discoideum.
Our RNA-seq data also showed that longer miRNA transcripts, generally preceded by
a T-rich putative promoter motif, accumulate in a drnB knock-out strain. For two
model miRNAs we defined the transcriptional start sites (TSSs) of primary (pri)
miRNAs and showed that they carry the RNA polymerase II specific m7G-cap. The
generation of the 3'-ends of these pri-miRNAs differs, with pri-mir-1177 reading
into the downstream gene, and pri-mir-1176 displaying a distinct end. This 3'-end
is processed to shorter intermediates, stabilized in DrnB-depleted cells, of
which some carry a short oligo(A)-tail. Furthermore, we identified 10 new miRNAs,
all DrnB dependent and developmentally regulated. Thus, the miRNA machinery in D.
discoideum shares features with both plants and animals, which is in agreement
with its evolutionary position and perhaps also an adaptation to its complex
lifestyle: unicellular growth and multicellular development.
PMID- 29966485
TI - The first report of genetic variations in the chicken prion protein gene.
AB - Abnormal structural changes of the prion protein (PrP) are the cause of prion
disease in a wide range of mammals. However, spontaneous infected cases have not
been reported in chicken. Genetic variations of the prion protein gene (PRNP) may
impact susceptibility to prion disease but have not been investigated thus far.
Because an investigation of the chicken PRNP can improve the understanding of
characteristics related to resistance to prion disease, research on the chicken
PRNP is highly desirable. In this study, we investigated the genetic
characteristics of the chicken PRNP gene. For this, we performed direct
sequencing in 106 Dekalb White chickens and analyzed the genotype and allele
frequencies of chicken PRNP gene. We found two insertion and deletion
polymorphisms in the chicken PRNP: c.163_180delAACCCAGGGTACCCCCAT and
c.268_269insC. The former is a U2 hexapeptide deletion polymorphism. Of the 106
samples, 13 (12.26%) were insertion homozygotes, 89 (83.96%) were heterozygotes,
and 4 (3.77%) were deletion homozygotes in c.163_180delAACCCAGGGTACCCCCAT. In the
c.268_269insC polymorphism, 102 (96.23%) were deletion homozygotes, and 4 (3.77%)
were heterozygotes. Insertion homozygotes of c.268_269insC were not detected. Two
polymorphisms were in perfect linkage disequilibrium (LD) with a D' value of 1.0,
and three haplotypes were identified. Furthermore, PROVEAN evaluates
163_180delAACCCAGGGTACCCCCAT as 'deleterious' with a score of - 13.173.
Furthermore, single nucleotide polymorphisms (SNPs) in the open reading frame
(ORF) of the PRNP gene were not found in the chicken. To the best of our
knowledge, this was the first report on the genetic variations of the chicken
PRNP gene.
PMID- 29966486
TI - Laparoscopic ligation of Type II endoleaks following endovascular aneurysm
repair: A systematic review.
AB - INTRODUCTION: The clinical significance of Type II endoleak remains contentious;
the strategies used for its management have continued to expand. We
systematically review the literature and comprehensively appraise the
effectiveness of laparoscopic intervention in the management of this common
complication. METHODS: A systematic search was performed in accordance to the
Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)
guidelines on MEDLINE, EMBASE and Cochrane Library for relevant articles
reporting laparoscopic surgery of Type II endoleak post-endovascular aortic
repair. RESULTS: Thirteen studies representing 40 patients were investigated.
Mean age was 72.7 years, and proportion of males was 90.0%. All patients were
American Society of Anesthesiologists grade II and above and underwent standard
infrarenal endovascular aneurysm repair. The mean duration of operation was 130.2
min, with a mean blood loss across of 173.8 mL. The overall technical success
rate was 90% (27/30). Two patients required reoperation within 24 h, with further
lumbar ligations that were successful. One other patient required conversion to
open surgery due to significant bleeding at the dorsal aorta. The perioperative
and 30-day mortality rate was 2.5% (1/40). The mean length of hospital stay was
3.7 days (range 1 to 10 days). The mean length of follow-up was 36.7 months
(range 3 to 103.2 months), where the rate of recurrence was 22.5% (9/40).
CONCLUSIONS: Laparoscopic ligation of feeding vessels causing Type II endoleak is
potentially an alternative treatment after failed standard endovascular
embolization, particularly in select centres with necessary resources and
capabilities.
PMID- 29966487
TI - The secondary prevention of venous thromboembolism: Towards an individual
therapeutic strategy.
AB - After the anticoagulant withdrawal, a substantial proportion of patients with
venous thromboembolism will develop recurrent events. Whether to consider an
extended treatment depends on the risk of recurrence and bleeding risk. The
assessment of the individual risk profile remains a difficult task. Several basal
and post-basal factors modulate the risk of recurrence and may help clinicians to
select patients who can benefit from the extended therapy. During the year 2017,
new evidence regarding the post-basal factors was provided by the Morgagni and
Scope studies. Another interesting novelty was the VTE-BLEED score, the first
bleeding risk score that obtained the external validation in venous
thromboembolism setting. In secondary prevention, the use of direct oral
anticoagulants is growing instead of vitamin K antagonist. Even at lower doses,
direct oral anticoagulants showed to be effective and safe, to reduce all-cause
mortality and seemed to be superior to placebo for the composite outcome of fatal
bleeding and fatal recurrence. After the recently published Einstein-Choice
trial, the role of aspirin has become truly marginal as rivaroxaban 10 mg showed
a bleeding risk similar to aspirin 100 mg but a greater effectiveness reducing
the relative risk of recurrence by about 70%. Another option for secondary
prevention could be sulodexide, with a lower protective effect than direct oral
anticoagulants but an interesting safety profile. In conclusion, in our opinion,
an individual strategy taking into account the risk of recurrence, bleeding risk,
therapeutic options and patient preferences is the most appropriate approach to
secondary prevention of venous thromboembolism.
PMID- 29966488
TI - Tinnitus: A Stepchild in Our Specialty.
AB - Many patients are not satisfied with their doctor's answer when they complain
about tinnitus. The proposed classification can be used to communicate with
patients as well as guide future research. Type A itemizes the treatable causes
of tinnitus. Type B itemizes tinnitus with a lack of medical explanation. Type C
tinnitus is caused by diagnosable and treatable conditions, as listed in tinnitus
type A, but the tinnitus persists after the successful treatment of the other
symptoms.
PMID- 29966489
TI - Ultrasound Supplemented by Sialendoscopy: Diagnostic Value in Sialolithiasis.
AB - Objective To assess the value of ultrasound, if indicated, supplemented by
sialendoscopy, in the diagnosis of sialolithiasis. Study Design Retrospective
study. Setting Referring center for salivary gland diseases. Subjects and Methods
All patients who presented with a suspected diagnosis of obstructive sialopathy
between January 2011 and April 2017 and had not undergone any treatment were
retrospectively evaluated. A total of 2052 patients and 2277 glands were included
in the study. Ultrasound examinations were carried out initially and followed by
sialendoscopy in all cases. Direct demonstration of sialothiasis by
sialendoscopy, transoral ductal surgery, and discharge of concrements/observation
of fragments during sialendoscopy after extracorporeal shock-wave lithotripsy
were regarded as definitive evidence of sialolithiasis. Results Ultrasound had an
accuracy, sensitivity, specificity, positive predictive value, and negative
predictive value of 94.77%, 94.91%, 94.57%, 96.14%, and 92.89%, respectively, for
the diagnosis of sialolithiasis. All false-positive findings were correctly
diagnosed, and in all false-negative findings, stones/fragments were visualized
by sialendoscopy. Over 95% of the false-negative findings in major salivary
glands (64/67) had visible ductal dilation in sonography, and in 73.1%, the
stones not detected on ultrasound were located in the distal part of the duct,
which is easily accessible with the sialendoscope. Conclusion This study shows
that sialolithiasis can be diagnosed using ultrasonography with a high degree of
certainty. If supplemented by sialendoscopy, the correct diagnosis could be
established in virtually all cases of sialolithiasis. Ultrasound supplemented by
sialendoscopy has the potential to serve as an alternative diagnostic standard in
the future.
PMID- 29966490
TI - Sample size for binary logistic prediction models: Beyond events per variable
criteria.
AB - Binary logistic regression is one of the most frequently applied statistical
approaches for developing clinical prediction models. Developers of such models
often rely on an Events Per Variable criterion (EPV), notably EPV >=10, to
determine the minimal sample size required and the maximum number of candidate
predictors that can be examined. We present an extensive simulation study in
which we studied the influence of EPV, events fraction, number of candidate
predictors, the correlations and distributions of candidate predictor variables,
area under the ROC curve, and predictor effects on out-of-sample predictive
performance of prediction models. The out-of-sample performance (calibration,
discrimination and probability prediction error) of developed prediction models
was studied before and after regression shrinkage and variable selection. The
results indicate that EPV does not have a strong relation with metrics of
predictive performance, and is not an appropriate criterion for (binary)
prediction model development studies. We show that out-of-sample predictive
performance can better be approximated by considering the number of predictors,
the total sample size and the events fraction. We propose that the development of
new sample size criteria for prediction models should be based on these three
parameters, and provide suggestions for improving sample size determination.
PMID- 29966491
TI - Development of the Greek version of the Face Name Associative Memory Exam (GR
FNAME12) in cognitively normal elderly individuals.
AB - OBJECTIVE: The Face-Name Associative Memory Examination (FNAME) is a cross-modal
associative memory test with a high sensitivity for detecting Alzheimer's disease
related subtle memory problems at an early preclinical stage. The present study
examined the psychometric characteristics of a Greek version of the short form of
FNAME (GR-FNAME12) to evaluate the contribution of demographic characteristics,
report the range of performance within our sample, and estimate regression-based
norms in cognitively normal elderly individuals. METHOD: In all, 216 cognitively
normal elderly individuals were recruited and were administered a version of the
short form of the FNAME (GR-FNAME12) that was culture and language specific to
Greek-speaking individuals and developed for this study. RESULTS: The construct
validity of GR-FNAME12 was determined using principal component analysis thereby
revealing two factors: face-name and face-occupation. These match the original
version of the test. A significant positive correlation between GR-FNAME12 and
two traditional memory measures - the RAVLT and the ROCFT - supported convergent
validity. Test-retest reliability was computed for 32 participants. Multiple
regression analyses showed that only age and not education or gender
significantly predicted performance on the GR-FNAME12. We also estimated
regression-based norms for the GR-FNAME12 scales. CONCLUSION: It was found that
the Greek version of the FNAME12 had adequate psychometric properties, and could
be administered to Greek-speaking individuals for clinical and research purposes.
PMID- 29966492
TI - East is not right: Spatial compatibility differs between egocentric and cardinal
retrieval.
AB - Four experiments examined perceptuo-motor associations involved in spatial
knowledge encoding and retrieval. Participants learned spatial information by
studying a map or by navigating through a real environment and then verified
spatial descriptions based on either egocentric or cardinal directional terms.
Participants moved the computer mouse to a YES or NO button to verify each
statement. We tracked mouse cursor trajectories to examine perceptuo-motor
associations in spatial knowledge. An encoding hypothesis predicts that perceptuo
motor associations depend on the involvement of perceptions and actions during
encoding, regardless of how spatial knowledge would be used. The retrieval
hypothesis predicts that perceptuo-motor associations change as a function of
retrieval demands, regardless of how they are learned. The results supported the
retrieval hypothesis. Participants showed action compatibility effects with
egocentric retrieval, regardless of how spatial information was learned. With
well-developed spatial knowledge, a reliable compatibility effect emerged during
egocentric retrieval, but no or limited compatibility effects emerged with
cardinal retrieval. With less-developed knowledge, the compatibility effects
evident during cardinal retrieval suggest a process of egocentric recoding. Other
factors of environment learning, such as location proximity and orientation
changes, also impacted the compatibility effect, as revealed in the temporal
dynamics of mouse movements. Taken together, the results demonstrate that
retrieval demands differentially rely upon perceptuo-motor associations in long
term spatial knowledge. This effect is also modulated by environment experience,
proximity of learned locations, and experienced orientations.
PMID- 29966493
TI - Sword bean variants and different pretreatments influence protein extraction and
protein properties.
AB - Two variants of the sword bean (Canavalia gladiata), namely the white sword bean
(WSB) and the red sword bean (RSB), are known. The MgCl2 concentration-dependent
canavalin solubility showed different behavior among the extracts from distinct
beans prepared by distinct pretreatments. Pretreatment and bean selection are
important factors for use in food chemical and biochemical experiments.
PMID- 29966494
TI - Age and sex-specific associations of carotid pulsatility with small vessel
disease burden in transient ischemic attack and ischemic stroke.
AB - Background Although large artery stiffness has been implicated in the
pathogenesis of cerebral small vessel disease, whether carotid pulsatility, a
convenient surrogate marker of arterial stiffness, is similarly associated with
global burden of small vessel disease is unknown. Aims To determine the age and
sex-specific associations of carotid pulsatility with global burden of small
vessel disease. Methods We studied consecutive patients with transient ischemic
attack or non-disabling ischemic stroke from the Oxford Vascular Study who had a
brain MRI and carotid duplex ultrasound during 2002-2014. We determined clinical
correlates of common carotid artery (CCA) and internal carotid artery (ICA)
pulsatility index (PI) and their associations with the total small vessel disease
score on MRI, stratified by age (median = 72). Results In 587 patients,
correlates of CCA and ICA-PI were both independently associated with age,
diabetes, and premorbid mean pulse pressure after adjustment for age, sex, and
cardiovascular risk factors (all p < 0.05). ICA-PI was strongly associated with
small vessel disease markers and burden, particularly lacunes, in patients
aged<70 (age and sex-adjusted odds ratio of top vs. bottom pulsatility index
quartile: 5.35, 1.95-14.70, p = 0.001; increasing small vessel disease score:
2.30, 1.01-5.25, p = 0.048), but not in patients aged >= 70 ( p > 0.05). No
associations between CCA-PI with small vessel disease score were noted at any
age. In 94 consecutive patients who also received transcranial Doppler
ultrasound, strong associations between middle cerebral artery (MCA)-PI and an
increasing small vessel disease score were noted (unadjusted OR-MCA: 4.26, 1.45
12.55, p = 0.009; ICA: 2.37, 0.81-6.87, p = 0.11; CCA: 1.33, 0.45-3.96, p=0.61).
Conclusions ICA and MCA-PI are associated with global small vessel disease
burden, especially in individuals aged<70 and may be causally related.
PMID- 29966495
TI - Determining nurses' perceptions of patient safety culture in palliative care
centres.
AB - BACKGROUND: Palliative care patients often do not have decision-making capacity
at the end of life so this patient group is vulnerable to violations of patient
safety. AIM: To determine the attitudes of nurses in palliative care centres in
Turkey towards the patient safety culture and to identify factors affecting
these. METHOD: A descriptive, cross-sectional design using self-report
questionnaires was used. RESULTS: The mean Patient Safety Culture Scale points of
the whole group were 2.91 +/- 0.44. In the sub-dimensions of the scale, the
highest points were determined in Employee Training (2.99 +/- 0.51) and the
lowest in Unexpected Events and Error Reporting (2.81 +/- 0.54). CONCLUSIONS:
Patient safety culture is related to nurses' working conditions and the attitude
of management towards errors, etc. The results of this study will provide a
contribution to the development of healthcare and healthcare training policies
for critical units vulnerable to patient safety violations.
PMID- 29966496
TI - Sexual and reproductive health and rights for all: translating the Guttmacher
Lancet Commission's global report to local action.
PMID- 29966497
TI - The Plication Technique to Enhance the Endoscopic Approach to Zenker's
Diverticulum.
AB - Endoscopic stapler approaches to Zenker's diverticulum often yield a persistent
diverticulum and recurrent dysphagia up to 20%. A novel technique to reduce the
postoperative diverticulum is described. Eight consecutive patients with Zenker's
diverticulum who underwent endoscopic stapler diverticulotomy had adjunctive
endoscopic plication of the diverticulum wall to functionally reduce the residual
diverticulum size. On postoperative esophagram, there was no visible diverticulum
in 4 of 7 patients (57%). The remaining 3 patients had a reduction in common wall
of 76%, 50%, and 40% with a mean postoperative size of 1.0 cm. All patients had
resolution or significant improvement in dysphagia. There were no complications
or recurrences at a mean follow-up of 6.3 months. As an adjunct to endoscopic
treatment of Zenker's diverticulum, the plication technique can reduce
diverticulum size. Further studies will determine if the plication technique
affects long-term recurrence of endoscopic stapler approaches.
PMID- 29966498
TI - Accountable Care Organizations and Post-Acute Care: A Focus on Preferred SNF
Networks.
AB - Due to high magnitude and variation in spending on post-acute care, accountable
care organizations (ACOs) are focusing on transforming management of hospital
discharge through relationships with preferred skilled nursing facilities (SNFs).
Using a mixed-methods design, we examined survey data from 366 respondents to the
National Survey of ACOs along with 16 semi-structured interviews with ACOs who
performed well on cost and quality measures. Survey data revealed that over half
of ACOs had no formal relationship with SNFs; however, the majority of ACO
interviewees had formed preferred SNF networks. Common elements of networks
included a comprehensive focus on care transitions beginning at hospital
admission, embedded ACO staff across settings, solutions to support information
sharing, and jointly established care protocols. Misaligned incentives, unclear
regulations, and a lack of integrated health records remained challenges, yet
preferred networks are beginning to transform the ACO post-acute care landscape.
PMID- 29966499
TI - Evaluating the effectiveness of a culturally adapted behavioral family psycho
educational program for Egyptian patients with schizophrenia.
AB - Although a growing body of evidence supports the effectiveness of behavioral
family therapies for patients with schizophrenia, few studies have been carried
out on the effectiveness of such programs for Egyptian patients. The current
study translated and culturally adapted the Behavioral Family Psycho-Education
Program (BFPEP) and conducted a preliminary efficacy evaluation for outpatients
suffering from schizophrenia. Thirty patients received 14 sessions of culturally
adapted Program (CA-BFPEP) and 30 received treatment as usual; all were followed
up for 6 months. Pre- and post-intervention assessment included primary outcome
measures that assessed the clinical, social, quality of life and attitude towards
medications. The CA-BFPEP group demonstrated significant treatment effects as
they had greater reductions in psychotic symptoms (PANSS), improvement of social
function (SFQ), quality of life (QoL), and attitude towards medications (DAI),
compared to patients in the control group. These results demonstrate the
feasibility of implementing family therapy interventions in different cultural
settings with relatively minor modifications. These promising findings invite
further efforts to maximize the benefits of family therapy interventions
internationally and to encourage mental health policy makers to integrate this
mode of therapy in routine care management plans for patients with schizophrenia.
PMID- 29966500
TI - Patient Reported Injuries After Ventral Hernia Repair.
AB - BACKGROUND AND AIMS: The Swedish National Patient Insurance Company (LOF) can
compensate patients who believe they have been exposed to an avoidable injury or
malpractice in healthcare. Its register covers 95% of Swedish healthcare
providers. MATERIAL AND METHODS: Data on patients operated for primary or
incisional ventral hernia in Sweden between 2010 and 2015 and who had filed a
claim, were retrieved from LOF. A total of 290 cases were identified and
included. Files include a copy of records, relevant imaging, and an expert
advisor's opinion. RESULTS: Inadvertent enterotomy occurred during 25 repairs and
in these cases, laparoscopic repair was clearly overrepresented ( p < 0.001).
Complications related to the surgical site (infection and ugly scar) were
predominantly related to open repairs ( p < 0.001). Twenty percentage (57/290)
of the claims were directly related to an anesthetic mishap. Univariate ordinal
regression showed that the odds of receiving a high reimbursement was
significantly increased if laparoscopic repair was performed p < 0.001 (odds
ratio: 0.37; 95% confidence interval: 0.21-0.65). Sixty-three percentage of
claims were filed by women. CONCLUSION: Inadvertent enterotomy is
overrepresented, and the probability that a claim filed for an avoidable injury
leads to high reimbursement is greater if laparoscopic repair is performed rather
than open ventral hernia repair. The high amount of injuries related to general
anesthesia during umbilical hernia repair may be reduced with an increased
proportion executed in local anesthesia.
PMID- 29966501
TI - Immunohistochemistry in Investigative and Toxicologic Pathology.
AB - Immunohistochemistry (IHC) is a valuable tool in pathology. This review provides
a brief description of the technical aspects of IHC and a detailed discussion on
the variables that affect the results, interpretation, and reproducibility of IHC
results. Lists of antibodies that have and have not worked in IHC on various
mouse and rat tissues in our laboratory are provided as a guidance for selection
of antibodies. An approach to IHC method optimization is presented. Finally, the
critical information that should be included as a part of peer-reviewed
manuscript is also discussed.
PMID- 29966502
TI - A Bayesian model to estimate the cutoff and the clinical utility of a biomarker
assay.
AB - To enable targeted therapies and enhance medical decision-making, biomarkers are
increasingly used as screening and diagnostic tests. When using quantitative
biomarkers for classification purposes, this often implies that an appropriate
cutoff for the biomarker has to be determined and its clinical utility must be
assessed. In the context of drug development, it is of interest how the
probability of response changes with increasing values of the biomarker. Unlike
sensitivity and specificity, predictive values are functions of the accuracy of
the test, depend on the prevalence of the disease and therefore are a useful tool
in this setting. In this paper, we propose a Bayesian method to not only estimate
the cutoff value using the negative and positive predictive values, but also
estimate the uncertainty around this estimate. Using Bayesian inference allows us
to incorporate prior information, and obtain posterior estimates and credible
intervals for the cut-off and associated predictive values. The performance of
the Bayesian approach is compared with alternative methods via simulation studies
of bias, interval coverage and width and illustrations on real data with binary
and time-to-event outcomes are provided.
PMID- 29966503
TI - The Pattern of Defects in Mesorectal Specimens: Is There a Difference between
Transanal and Laparoscopic Approaches?
AB - BACKGROUND: Total mesorectal excision has evolved from open to minimally invasive
techniques. To overcome difficulties in the lowest part of the pelvis, transanal
total mesorectal excision was introduced and has gained acceptance in the recent
years. The results of transanal total mesorectal excision seem to be comparable
to laparoscopic total mesorectal excision. Whether or not transanal total
mesorectal excision has changed the pattern of defects in the retrieved
mesorectal specimens is yet to be clarified. PURPOSE: To determine the pattern of
mesorectal defects following transanal total mesorectal excision, compared to
laparoscopic total mesorectal excision. The primary end-point was the location of
defects in the part of the mesorectum below the peritoneal reflection, as it is
this part, which is dissected from below in the transanal total mesorectal
excision procedure. METHODS: From our transanal total mesorectal excision
database that includes all transanal total mesorectal excision procedures
performed at our institution since 2013, we have included 29 patients who
originally had defects in their retrieved specimens. Another 29 patients who
underwent laparoscopic total mesorectal excision with mesorectal defects served
as a control group. All specimen photos and pathology reports were reviewed
systematically; sites and pattern of defects were defined. RESULTS: A higher
ratio of the defects in the laparoscopic total mesorectal excision group was
located below the peritoneal reflection (P = 0.043). The distribution of defects
by anatomical quadrant was not statistically different between the groups.
CONCLUSIONS: The ratio of defects below the peritoneal reflection was lower in
the transanal total mesorectal excision group. Whether this is due to a lower
incidence of defect in transanal total mesorectal excision is not part of our
study.
PMID- 29966504
TI - Purification, cDNA cloning, and characterization of plant chitinase with a novel
domain combination from lycophyte Selaginella doederleinii.
AB - : Chitinase-A from a lycophyte Selaginella doederleinii (SdChiA), having
molecular mass of 53 kDa, was purified to homogeneity by column chromatography.
The cDNA encoding SdChiA was cloned by rapid amplification of cDNA ends and
polymerase chain reaction. It consisted of 1477 nucleotides and its open reading
frame encoded a polypeptide of 467 amino acid residues. The deduced amino acid
sequence indicated that SdChiA consisted of two N-terminal chitin-binding domains
and a C-terminal plant class V chitinase catalytic domain, belonging to the
carbohydrate-binding module family 18 (CBM18) and glycoside hydrolase family 18
(GH18), respectively. SdChiA had chitin-binding ability. The time-dependent
cleavage pattern of (GlcNAc)4 by SdChiA showed that SdChiA specifically
recognizes the beta-anomer in the + 2 subsite of the substrate (GlcNAc)4 and
cleaves the glycoside bond at the center of the substrate. This is the first
report of the occurrence of a family 18 chitinase containing CBM18 chitin-binding
domains. ABBREVIATIONS: AtChiC: Arabidopsis thaliana class V chitinase; CBB:
Coomassie brilliant blue R250; CBM: carbohydrate binding module family; CrChi-A:
Cycas revolute chitinase-A; EaChiA: Equisetum arvense chitinase-A; GH: glycoside
hydrolase family, GlxChi-B: gazyumaru latex chitinase-B; GlcNAc: N
acetylglucosamine; HPLC: high performance liquid chromatography; LysM; lysin
motif; MtNFH1: Medicago truncatula ecotypes R108-1 chitinase; NCBI: national
center for biotechnology information; NF: nodulation factor; NtChiV: Nicotiana
tabacum class V chitinase; PCR: polymerase chain reaction; PrChi-A: Pteris
ryukyuensis chitinase-A; RACE: rapid amplification of cDNA ends; SDS-PAGE: sodium
dodecyl sulfate-polyacrylamide gel electrophoresis; SdChiA: Selaginella
doederleinii chitinase-A.
PMID- 29966505
TI - Statistical Guidance for Reviewers of Toxicologic Pathology.
AB - Study design, statistical analysis, interpretation of results, and conclusions
should be a part of all research papers. Statistics are integral to each of these
components and are therefore necessary to evaluate during manuscript peer review.
Research published in Toxicological Pathology is often focused on animal studies
that may seek to compare defined treatment groups in randomized controlled
experiments or focus on the reliability of measurements and diagnostic accuracy
of observed lesions from preexisting studies. Reviewers should distinguish
scientific research goals that aim to test sufficient effect size differences
(i.e., minimizing false positive rates) from common toxicologic goals of
detecting a harmful effect (i.e., minimizing false negative rates). This journal
comprises a wide range of study designs that require different kinds of
statistical assessments. Therefore, statistical methods should be described in
enough detail so that the experiment can be repeated by other research groups.
The misuse of statistics will impede reproducibility.
PMID- 29966506
TI - Cervical cancer screening among transactional female sex workers in the Dominican
Republic.
AB - Cervical cancer is the third leading cause of cancer-related death and the second
most diagnosed cancer among women in developing countries. We determined the
prevalence of abnormal Papanicolaou (Pap), high-risk HPV (hrHPV), and colposcopy
among transactional female sex workers (FSWs) in La Romana, Dominican Republic.
The results of 144 FSWs of ages 18-54 years who completed a demographic interview
and Pap testing with hrHPV detection between June 2015 and April 2016 were
analyzed. Women with abnormal results were referred for colposcopy. Risk factors
for abnormal Pap were assessed through bivariate and multivariate analyses.
Overall, 36.1% (52/144) of Paps were abnormal and 43.4% (62/143) had hrHPV. Of
all women with hrHPV and/or abnormal Pap (68/144; 47.2%), 61 (89.7%) were
referred and 16 (26.2) underwent colposcopy. HPV16 and/or 18/45 was detected in
33.3% (15/45) of low-grade Paps. Binge drinking, weekly (AOR 5.1, 95% CI: 1.8
14.5) or daily (AOR 4.9, 95% CI: 1.5-16.6), and age at first sexual relation (AOR
1.2, 95% CI: 1.0-1.5) were significantly associated ( p < 0.05) with abnormal
Pap. Although almost half of participants had abnormal Pap or hrHPV, few
underwent colposcopy. Improving access to cervical cancer screening and follow-up
for FSWs is imperative.
PMID- 29966507
TI - Cryptococcal meningitis: an unusual presentation of primary HIV infection.
AB - Acute HIV infection presenting as severe opportunistic disease is a very uncommon
event associated with more rapid HIV progression and higher mortality. We
describe the case of a patient with cryptococcal meningitis in the setting of
primary HIV infection.
PMID- 29966508
TI - Sociodemographic and behavioural factors associated with body mass index among
men and women in Nairobi slums: AWI-Gen Project.
AB - BACKGROUND: Body mass index (BMI) is rising globally with a faster increase in
urban areas in low- and middle-income countries. It is critical to identify
modifiable risk factors for BMI to prevent the occurrence of associated health
consequences. OBJECTIVE: To investigate socio-demographic, behavioural and
biological factors associated with BMI in Nairobi slums. METHODS: In 2014-2015, a
cross sectional study of men and women aged 40-60 years in Nairobi slums
(Korogocho and Viwandani) was conducted. Data were collected on socio
demographic, behavioural and biological characteristics. Mean BMI, overweight and
obesity were computed. Hierarchical multiple linear regression analysis was
conducted separately for men and women to explore factors associated with BMI.
RESULTS: In total, 1942 study participants (54.4%, women) with a mean age (SD) of
48.3 (5.3) years and 48.8(5.6) years for women and men respectively were
recruited. Mean BMI was higher among women than men (27.6 versus 22.8; p <
0.001). More women were overweight (30.9% versus 19.6%; p < 0.001) and obese
(32.1% versus 5.1%; p < 0.001) than men. Among men, BMI was independently
associated with wealth index, bread consumption and self-reported diabetes and
was negatively associated with current tobacco smoking, HIV and TB infections.
Among women, BMI was independently associated with wealth, current non
problematic drinking, and sedentary time, but was lower among other ethnicities
compared to Kikuyu, among current smokers, women with longer sleep, and those
with HIV infection and tuberculosis. Wealth index contributed the most variance
in BMI among women and men (10.4%, 7.5%, respectively), but behavioural factors
(7.4%) among men and biological factors (6.5%) among women accounted for most of
the additional BMI variance. CONCLUSIONS: Adults aged 40-60 years in the urban
slums of Nairobi have a high BMI associated with wealth. Bread consumption by men
and sedentary life among women are the main risky behaviours that need urgent
targeted interventions.
PMID- 29966509
TI - HIV-1 TAT-mediated microglial activation: role of mitochondrial dysfunction and
defective mitophagy.
AB - : While the advent of combination antiretroviral therapy (cART) has dramatically
increased the life expectancy of HIV-1 infected individuals, paradoxically,
however, the prevalence of HIV-1-associated neurocognitive disorders is on the
rise. Based on the premise that the cytotoxic HIV-1 protein, transactivator of
transcription (TAT), a known activator of glial cells that is found to persist in
the central nervous system (CNS) despite cART, we sought to explore the role of
defective mitophagy in HIV-1 TAT-mediated microglial activation. Our results
demonstrated that exposure of mouse primary microglia to HIV-1 TAT resulted in
cellular activation involving altered mitochondrial membrane potential that was
accompanied by accumulation of damaged mitochondria. Exposure of microglia to HIV
1 TAT resulted in increased expression of mitophagy signaling proteins, such as
PINK1, PRKN, and DNM1L, with a concomitant increase in the formation of
autophagosomes, as evidenced by increased expression of BECN1 and MAP1LC3B-II.
Intriguingly, exposure of cells to HIV-1 TAT also resulted in increased
expression of SQSTM1, signifying thereby a possible blockade of the mitophagy
flux, leading, in turn, to the accumulation of mitophagosomes. Interestingly, HIV
1 TAT-mediated activation of microglia was associated with decreased rate of
extracellular acidification and mitochondrial oxygen consumption and increased
expression of proinflammatory cytokines, such as Tnf, Il1b, and Il6. HIV-1 TAT
mediated defective mitophagy leading to microglial activation was further
validated in vivo in the brains of HIV-1 transgenic rats. In conclusion, HIV-1
TAT activates microglia by increasing mitochondrial damage via defective
mitophagy. ABBREVIATIONS: 3-MA: 3-methyladenine; Deltapsim: mitochondrial
membrane potential; ACTB: actin, beta; AIF1: allograft inflammatory factor 1;
ATP: adenosine triphosphate; BAF: bafilomycin A1; BECN1: beclin 1, autophagy
related; cART: combined antiretroviral therapy; CNS: central nervous system;
DNM1L: dynamin 1 like; DMEM: Dulbecco modified Eagle medium; DAPI: 4,6-diamidino
2-phenylindole; ECAR: extracellular acidification rate; FBS: fetal bovine serum;
FCCP: trifluoromethoxy carbonylcyanide phenylhydrazone; GAPDH: glyceraldehyde-3
phosphate dehydrogenase; HAND: HIV-1-associated neurocognitive disorders; HIV-1
TAT: human immunodeficiency virus-1 transactivator of transcription; IL1B:
interleukin 1, beta; IL6: interleukin 6; ITGAM: integrin subunit alpha M;
MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; mPMs: mouse
primary microglial cells; MRC: maximal respiratory capacity; mt-CO1:
mitochondrially encoded cytochrome c oxidase; mt-ND6: mitochondrially encoded
NADH:ubiquinone oxidoreductase core subunit 6; NFKB1: nuclear factor kappa B
subunit 1; NLRP3: NLR family pyrin domain containing 3; OCR: oxygen consumption
rate; PBS: phosphate-buffered saline; PINK1: PTEN induced putative kinase 1;
PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species;
siRNA: small interfering RNA; SQSTM1: sequestosome 1; TNF: tumor necrosis factor.
PMID- 29966510
TI - Integrated problem-based learning versus lectures: a path analysis modelling of
the relationships between educational context and learning approaches.
AB - Students' approaches to learning are central to the process of learning. Previous
research has revealed that influencing students' approaches towards deep learning
is a complex process and seems much more difficult than expected, even in student
activating learning environments. There is evidence that learning approaches are
impacted not only by the learning environment, but also by how students perceive
it. However the nature of the links between the environment itself, the way in
which it is perceived by students and students' learning approaches is poorly
understood. This study aimed at investigating the relationships between students'
perception of their educational context and learning approaches in three learning
environments differing by their teaching formats (lecture or problem-based
learning PBL) and integration level of the curriculum (traditional or
integrated). We tested the hypothesis that a PBL format and an integrated
curriculum are associated to deeper approaches to learning and that this is
mediated by student perception. The study sample was constituted of 1394 medical
students trained respectively in a traditional lecture-based (n = 295), in an
integrated lecture-based (n = 612) and in an integrated PBL-based (n = 487)
curricula. They completed a survey including the Dundee-Ready-Educational
Environment-Measure (students' perceptions of the educational environment) and
the Revised-Study-Process-Questionnaire (learning approaches). Data were analysed
by path analysis. The model showed that the learning environment was related to
students' learning approaches by two paths, one direct and one mediated via
students' perception of their educational context. In the lecture-based curricula
students' used deeper approaches when it was integrated and both paths were
cumulative. In the PBL-based curriculum students' did not use deeper approaches
than with lectures, due to opposite effects of both paths. This study suggested
that an integrated lecture-based curriculum was as effective as a PBL curriculum
in promoting students' deep learning approaches, reinforcing the importance of
integrating the curriculum before choosing the teaching format.
PMID- 29966511
TI - Proposal of indicators for healthcare waste management: Case of a Brazilian
public institution.
AB - Healthcare waste (HCW) management represents a big challenge for managers around
the world. Segregation is a fundamental action to allow the risk management
inherent to each type of wastes. HCW indicators may favour the understanding of
the waste management system status. The aim of this paper is to evaluate the HCW
indicators applied in a Brazilian public institution, seeking to improve the
management system and suggesting methods of applying this tool as an alternative
of continuous improvement to the management process. Wastes were weighed every
trimester for seven consecutive days, between of 2012 to 2017. The data represent
daily, monthly and quarterly averages of the waste generated. Group B (chemical)
and Group E (sharps) indicators had statistical non-significant data, suggesting
very distant results from the stipulated goal. The generation rate was 355.3
500.7 kg.day-1 including all types of waste. Considering the approximate values
of the non-infected wastes, which may be discarded in a landfill, the percentage
represents about 75% of all HCW generated. The other 25% need to be treated at
cost of $US0.76kg-1. An effectively dangerous portion of the infectious waste
would be approximately 6%. Failures in segregation could represent, in addition
to the health risks, unnecessary expenses of the generating establishments. HCW
indicators have good potential to provide adequate risk management in health
service environments.
PMID- 29966513
TI - Correction to: Realizing drug repositioning by adapting a recommendation system
to handle the process.
AB - Following publication of the original article [1], the authors reported that
there was an error in the spelling of the name of one of the authors.
PMID- 29966512
TI - Phosphate binders as a cause of hypothyroidism in dialysis patients: practical
indications from a review of the literature.
AB - BACKGROUND: Although fatigue is common in dialysis patients, polypharmacy is
seldom listed among its causes. In this report, we describe a dialysis patient
who developed severe fatigue due to pharmacological interaction between two
commonly prescribed drugs, phosphate binders and levothyroxine. CASE
PRESENTATION: A 65-year old woman, on dialysis for 17 years, complained of
fatigue (weight 54 Kg, height 1.55 m, BMI: 23 Kg/m2; malnutrition inflammation
index: 10; Charlson index 9). She had been treated with lithium for about 20
years. A heavy smoker, she was obese and diabetic when young, but stopped
treatment after weight loss. She had undergone thyroidectomy for papillary
carcinoma, left hemicolectomy for colon adenocarcinoma, left quadrantectomy
followed by radiotherapy for ductal mammary adenocarcinoma, subtotal
parathyroidectomy for tertiary hyperparathyroidism. At the time of this report,
she was on thrice-weekly hemodiafiltration (Daugirdas 2 Kt/V: 1.6-1.8). Her
recent treatment included spironolactone, amlodipine, perindopril, valproate,
lamotrigine, levothyroxine, vitamin D, calcium carbonate, sodium polystyrene and
sevelamer. After she questioned her doctor about whether her fatigue might be the
result of a drug interaction, levothyroxine interference was identified (TSH,
previously normal, increased to 13.07 mU/L, after increasing sevelamer dose, and
normalized after change of drug schedule). LITERATURE REVIEW: only 5 relevant
papers on levothyroxine and phosphate binders on dialysis were found on Pubmed
and EMBASE (out of 351 titles retrieved). Information was therefore inferred from
studies in normal volunteers or in other diseases. DISCUSSION AND CONCLUSIONS:
Our case differs from other reports on lower TSH at diagnosis, underlining the
need for awareness of the importance of early diagnosis. Integrating the scant
literature on dialysis patients with data available in the general population,
some working conclusions can be reached: while all phosphate binders potentially
interfere with levothyroxine absorption, interference seems to be highest for
sevelamer; interference is limited but not excluded by increasing the intervals
between drugs; morning fast is usually indicated but, when clashing with the
timing of other drugs, a bedtime dose and liquid preparations may be indicated.
In the absence of an agreed control schedule, our case supports close monitoring
of TSH (1-3 months if unstable, twice-yearly in stable patients).
PMID- 29966514
TI - Transcriptomics comparison reveals the diversity of ethylene and methyl-jasmonate
in roles of TIA metabolism in Catharanthus roseus.
AB - BACKGROUND: The medicinal plant, Catharanthus roseus (C. roseus), accumulates a
wide range of terpenoid indole alkaloids (TIAs). Ethylene (ET) and methyl
jasmonate (MeJA) were previously reported as effective elicitors for the
production of various valuable secondary metabolites of C. roseus, while a few ET
or MeJA induced transcriptomic research is yet reported on this species. In this
study, the de-novo transcriptome assembly of C. roseus is performed by using the
next-generation sequencing technology. RESULTS: The result shows that phenolic
biosynthesis genes respond specifically to ET in leaves, monoterpenoid
biosynthesis genes respond specifically to MeJA in roots. By screening the
database, 23 ATP-binding cassette (ABC) transporter partial sequences are
identified in C. roseus. On this basis, more than 80 key genes that encode key
enzymes (namely TIA pathway, transcriptional factor (TF) and candidate ABC
transporter) of alkaloid synthesis in TIA biosynthetic pathways are chosen to
explore the integrative responses to ET and MeJA at the transcriptional level.
Our data indicated that TIA accumulation is strictly regulated by the TF ethylene
responsive factor (ERF) and bHLH iridoid synthesis 1 (BIS1). The heatmap,
combined with principal component analysis (PCA) of C. roseus, shows that ERF co
expression with ABC2 and ABC8 specific expression in roots affect the root
specific accumulation of vinblastine in C. roseus. On the contrast, BIS1
activities follow a similar pattern of ABC3 and CrTPT2 specific expression in
leaves, which affects the leaf-specific accumulation of vindoline in C. roseus.
CONCLUSIONS: Results presented above illustrate that ethylene has a stronger
effect than MeJA on TIA induction at both transcriptional and metabolite level.
Furthermore, meta-analysis reveals that ERF and BIS1 form a positive feedback
loop connecting two ABC transporters respectively and are actively involved in
TIAs responding to ET and MeJA in C. roseus.
PMID- 29966515
TI - Newborn weight change and childhood cardio-metabolic traits - a prospective
cohort study.
AB - BACKGROUND: Newborn weight change (NWC) in the first 4 days represents short-term
adaptations to external environment. It may be a key developmental period for
future cardio-metabolic health, but this has not been explored. We aimed to
determine the associations of NWC with childhood cardio-metabolic traits.
METHODS: As part of Generation XXI birth cohort, children were recruited in
2005/2006 at all public units providing obstetrical and neonatal care in Porto.
Birthweight was abstracted from clinical records and postnatal anthropometry was
obtained by trained examiners during hospital stay. NWC was calculated as
((minimum weight - birthweight)/birthweight) * 100. At age 4 and 7, children were
measured and had a fasting blood sample collected. Fasting glucose, LDL
cholesterol, triglycerides, waist circumference, systolic and diastolic blood
pressure were evaluated. This study included 312 children with detailed
information on growth in very early life and subsequent cardio-metabolic
measures. Path analysis was used to compute adjusted regression coefficients and
95% confidence intervals. RESULTS: NWC was not associated with any cardio
metabolic traits at ages 4 or 7. Strong associations were observed between each
cardio-metabolic trait at 4 with the same trait at 7 years. The strongest
associations were found for waist circumference [0.725 (0.657; 0.793)] and LDL
cholesterol [0.655 (0.575; 0.735)]. CONCLUSIONS: No evidence that NWC is related
to childhood cardio-metabolic traits was found, suggesting that NWC should be
faced in clinical practice as a short-term phenomenon, with no medium/long term
consequences, at least in cardio-metabolic health. Our results show strong
tracking correlations in cardio-metabolic traits during childhood.
PMID- 29966516
TI - Cost-effectiveness of a potential Zika vaccine candidate: a case study for
Colombia.
AB - BACKGROUND: A number of Zika vaccine platforms are currently being investigated,
some of which have entered clinical trials. We sought to evaluate the cost
effectiveness of a potential Zika vaccine candidate under the WHO Vaccine Target
Product Profile for outbreak response, prioritizing women of reproductive age to
prevent microcephaly and other neurological disorders. METHODS: Using an agent
based simulation model of ZIKV transmission dynamics in a Colombian population
setting, we conducted cost-effectiveness analysis with and without pre-existing
herd immunity. The model was parameterized with estimates associated with ZIKV
infection, risks of microcephaly in different trimesters, direct medical costs,
and vaccination costs. We assumed that a single dose of vaccine provides a
protection efficacy in the range 60% to 90% against infection. Cost-effectiveness
analysis was conducted from a government perspective. RESULTS: Under a favorable
scenario when the reproduction number is relatively low (R0 = 2.2) and the
relative transmissibility of asymptomatic infection is 10% compared with
symptomatic infection, a vaccine is cost-saving (with negative incremental cost
effective ratio; ICER) for vaccination costs up to US$6 per individual without
herd immunity, and up to US$4 per individual with 8% herd immunity. For positive
ICER values, vaccination is highly cost-effective for vaccination costs up to
US$10 (US$7) in the respective scenarios with the willingness-to-pay of US$6610
per disability-adjusted life-year, corresponding to the average per capita GDP of
Colombia between 2013 and 2017. Our results indicate that the effect of other
control measures targeted to reduce ZIKV transmission decreases the range of
vaccination costs for cost-effectiveness due to reduced returns of vaccine
induced herd immunity. In all scenarios investigated, the median reduction of
microcephaly exceeded 64% with vaccination. CONCLUSIONS: Our study suggests that
a Zika vaccine with protection efficacy as low as 60% could significantly reduce
the incidence of microcephaly. From a government perspective, Zika vaccination is
highly cost-effective, and even cost-saving in Colombia if vaccination costs per
individual is sufficiently low. Efficacy data from clinical trials and number of
vaccine doses will be important requirements in future studies to refine our
estimates, and conduct similar studies in other at-risk populations.
PMID- 29966517
TI - Evaluation of a commercial multi-dimensional echocardiography technique for
ventricular volumetry in small animals.
AB - BACKGROUND: The assessment of ventricular volumes using conventional
echocardiography methods is limited with regards to the need of geometrical
assumptions. In the present study, we aimed to evaluate a novel commercial system
for three-dimensional echocardiography (3DE) in preclinical models by direct
comparison with conventional 1D- and 2D-echocardiography (1DE; 2DE) and the gold
standard technique magnetic resonance imaging (MRI). Further, we provide a
standard operating protocol for image acquisition and analysis with 3DE. METHODS:
3DE was carried out using a 30 MHz center frequency transducer coupled to a
Vevo(r)3100 Imaging System. We evaluated under different experimental conditions:
1) in vitro phantom measurements served as controlled setting in which boundaries
were clearly delineated; 2) a validation cohort composed of healthy C57BL/6 J
mice and New Zealand Obese (NZO) mice was used in order to validate 3DE against
cardiac MRI; 3) a standard mouse model of pressure overload induced-heart failure
was investigated to estimate the value of 3DE. RESULTS: First, in vitro volumetry
revealed good agreement between 3DE assessed volumes and the MRI-assessed
volumes. Second, cardiac volume determination with 3DE showed smaller mean
differences compared to cardiac MRI than conventional 1DE and 2DE. Third, 3DE was
suitable to detect reduced ejection fractions in heart failure mice. Fourth,
inter- and intra-observer variability of 3DE showed good to excellent agreement
regarding absolute volumes in healthy mice, whereas agreement rates for the
relative metrics ejection fraction and stroke volume demonstrated good to
moderate observer variabilities. CONCLUSIONS: 3DE provides a novel method for
accurate volumetry in small animals without the need for spatial assumptions,
demonstrating a technique for an improved analysis of ventricular function.
Further validation work and highly standardized image analyses are required to
increase reproducibility of this approach.
PMID- 29966518
TI - Inhibition of integrin alphaVbeta6 changes fibril thickness of stromal collagen
in experimental carcinomas.
AB - BACKGROUND: Chemotherapeutic efficacy can be improved by targeting the structure
and function of the extracellular matrix (ECM) in the carcinomal stroma. This can
be accomplished by e.g. inhibiting TGF-beta1 and -beta3 or treating with
Imatinib, which results in scarcer collagen fibril structure in xenografted human
KAT-4/HT29 (KAT-4) colon adenocarcinoma. METHODS: The potential role of
alphaVbeta6 integrin-mediated activation of latent TGF-beta was studied in
cultured KAT-4 and Capan-2 human ductal pancreatic carcinoma cells as well as in
xenograft carcinoma generated by these cells. The monoclonal alphaVbeta6 integrin
specific monoclonal antibody 3G9 was used to inhibit the alphaVbeta6 integrin
activity. RESULTS: Both KAT-4 and Capan-2 cells expressed the alphaVbeta6
integrin but only KAT-4 cells could utilize this integrin to activate latent TGF
beta in vitro. Only when Capan-2 cells were co-cultured with human F99
fibroblasts was the integrin activation mechanism triggered, suggesting a more
complex, fibroblast-dependent, activation pathway. In nude mice, a 10-day
treatment with 3G9 reduced collagen fibril thickness and interstitial fluid
pressure in KAT-4 but not in the more desmoplastic Capan-2 tumors that, to
achieve a similar effect, required a prolonged 3G9 treatment. In contrast, a 10
day direct inhibition of TGF-beta1 and -beta3 reduced collagen fibril thickness
in both tumor models. CONCLUSION: Our data demonstrate that the alphaVbeta6
directed activation of latent TGF-beta plays a pivotal role in modulating the
stromal collagen network in carcinoma, but that the sensitivity to alphaVbeta6
inhibition depends on the simultaneous presence of alternative paths for latent
TGF-beta activation and the extent of desmoplasia.
PMID- 29966519
TI - Association of white matter hyperintensities with migraine features and
prognosis.
AB - BACKGROUND: White matter hyperintensities (WMHs) are frequently detected in
migraine patients. However, their significance and correlation to migraine
disease burden remain unclear. This study aims to examine the correlation of WMHs
with migraine features and explore the relationship between WMHs and migraine
prognosis. METHODS: A total of 69 migraineurs underwent MRI scans to evaluate
WMHs. Migraine features were compared between patients with and without WMHs.
After an average follow-up period of 3 years, these patients were divided into
two groups, according to the reduction of headache frequency: improved and non
improved groups. The percentage and degree of WMHs were compared between these
two groups. RESULTS: A total of 24 patients (34.8%) had WMHs. Patients with WMHs
were significantly older (39.0 +/- 7.9 vs. 30.6 +/- 10.4 years, P < 0.001) and
had a longer disease duration (median: 180.0 vs. 84.0 months, P = 0.013).
Furthermore, 33 patients completed the follow up period (15 patients improved and
18 patients did not improve). Patients in the non-improved group had a higher
frequency of WMHs (55.6% vs. 13.3%, P = 0.027) and median WMHs score (1.0 vs.
0.0, P = 0.030). CONCLUSIONS: WMHs can predict unfavorable migraine prognosis.
Furthermore, WMHs may have a closer association with age than migraine features.
PMID- 29966520
TI - Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD
1/anti-CTLA-4) in metastatic malignant melanoma.
AB - BACKGROUND: Metformin is one of the biguanides commonly used in patients with
type II Diabetes Mellitus. Apart from its hypoglycemic properties, metformin also
inhibits the cell cycle by restricting protein synthesis and cell proliferation
via regulating the LKB1/AMPL pathway. Furthermore, it also enhances the PD-1
blockade through a reduction of tumor hypoxia. Metformin has shown a significant
favorable impact on treatment-related outcomes in solid tumors, but these
outcomes have not been replicated in the limited clinical studies done on
malignant melanoma. Moreover, none of these studies have reported on the efficacy
of the combined use of metformin and immune checkpoint inhibitors (ICIs).
METHODS: This is a retrospective cohort study that includes patients diagnosed
with metastatic malignant melanoma and treated with ipilimumab, nivolumab, and/or
pembrolizumab (Cohort A); or ipilimumab, nivolumab, and/or pembrolizumab plus
metformin (Cohort B) between January 1st 2011 through December 15th 2017. In this
study, patients are stratified based on anti-PD-1 only and anti-CTLA4/anti-PD-1
combination therapies in each cohort. Objective response rate (ORR) is the
primary endpoint. Disease control rate (DCR), overall survival (OS) and
progression-free survival (PFS) are the secondary endpoints. RESULTS: Cohort A
had 33 patients (60%), while cohort B had 22 (40%). Overall patient
characteristics were similar between both cohorts. ORR was higher in cohort B
(68.2% vs. 54.5%, P = 0.31). The DCR was higher in cohort B as well (77.3% vs.
60.6%, P = 0.19). Median OS (46.7 months vs. 28 months), and median PFS (19.8
months vs. 5 months) were longer in cohort B. However, on univariate and
multivariate analyses, none of these differences were statistically significant.
The mean number of new metastatic sites which appeared during therapy were
significantly higher in cohort A (A:1.51 vs. B:0.59, P = 0.009). CONCLUSION: We
have observed favorable treatment-related outcomes (ORR, DCR, median PFS and
median OS) in patients who have received metformin in combination with ICIs
without reaching significance, probably, due to small sample size. Hence, large
prospective clinical trials are required to study the synergistic effect of
metformin in combination with ICIs before it can be recommended as routine
additive therapy.
PMID- 29966521
TI - "It doesn't exist...": negotiating palliative care from a culturally and
linguistically diverse patient and caregiver perspective.
AB - BACKGROUND: The end of life represents a therapeutic context that acutely raises
cultural and linguistic specificities, yet there is very little evidence
illustrating the importance of such dynamics in shaping choices, trajectories and
care practices. Culture and language interplay to offer considerable potential
challenges to both patient and provider, with further work needed to explore
patient and caregiver perspectives across cultures and linguistic groups, and
provider perspectives. The objective of this study was to develop a critical,
evidence-based understanding of the experiences of people from Culturally and
Linguistically Diverse (CALD) backgrounds, and their caregivers, in a palliative
care setting. METHODS: A qualitative study, using semi-structured interviews to
explore key experiences and perspectives of CALD patients and caregivers
currently undergoing treatment under oncology or palliative care specialists in
two Australian hospitals. Interviews were digitally audio recorded and
transcribed in full. A thematic analysis was conducted utilising the framework
approach. RESULTS: Sixteen patients and fourteen caregivers from a range of CALD
backgrounds participated in semi-structured interviews. The research identified
four prevalent themes among participants: (1) Terminology in the transition to
palliative care; (2) Communication, culture and pain management; (3) (Not)
Talking about death and dying; and, (4) Religious faith as a coping strategy:
challenging the terminal diagnosis. CONCLUSIONS: CALD patients and caregivers'
experiences are multifaceted, particularly in negotiating linguistic
difficulties, beliefs about treatment, and issues related to death and dying.
Greater attention is needed to develop effective communication skills, recognise
CALD patients' particular cultural, linguistic and spiritual values and needs,
and acknowledge the unique nature of each doctor-patient interaction.
PMID- 29966523
TI - Correction to: Limited utility of tissue micro-arrays in detecting intra-tumoral
heterogeneity in stem cell characteristics and tumor progression markers in
breast cancer.
AB - Following publication of the original article [1], a typesetting mistake is
reported. For Fig. 7b, a copy of Fig. 6b has been published. The correct Fig. 7b
is given in this correction and the original article has been updated.
PMID- 29966522
TI - The KT Jeang Retrovirology prize 2018: Eric Freed.
PMID- 29966524
TI - Oncocytoma managed by active surveillance in a transplant allograft kidney: a
case report.
AB - BACKGROUND: The ethical implications of the utilization of kidneys with solid
renal masses (SRMs) in transplantation are the subject of lively debate in the
transplantation community and beyond. One of such implications is that as the
life expectancy of renal transplant patients improve, the prevalence of SRMs in
donors is likely to increase. We report a case of an oncocytoma in a renal
allograft complicating a deceased-donor kidney transplant. CASE PRESENTATION: A
60-year-old woman received and underwent deceased-donor renal transplantation for
end-stage renal disease after a waiting-list period of 11 years. Kidney Doppler
ultrasound (DUS) of the deceased donor was negative for any nodular lesion. The
finding of the DUS, done on postoperative day 1, to assess the patency of the
graft, was suspicious for an acute arterial thrombosis but did not reveal any
focal irregularities. An ensuing computed tomography (CT) scan did not show any
arterial complications but serendipitously revealed a 2.4-cm lesion on the upper
pole of the renal allograft, which was not detected during the back-table or
ultrasonography monitoring. Histology of the biopsied lesion was consistent with
oncocytoma. However, because the eosinophilic variant of chromophobe renal cell
carcinoma may morphologically resemble renal oncocytoma, immunohistochemical
staining was performed. The results were negative, ruling out chromophobe RCC.
After discussing the therapeutic options and potential related outcomes with the
patient, we found no reason for resection of the lesion or an allograft
nephrectomy, given the low risk of malignant transformation in an oncocytoma.
Active surveillance of the benign tumor was done with ultrasonography, every 2
months, for the first year and, then, with magnetic resonance imaging, every
year. The patient received mycophenolate-mofetil, tacrolimus, and prednisone
throughout the 5-year follow-up period, and the regimen for immunosuppression was
not changed despite the presence of the renal mass. After 60 months, we report
that none of the radiological findings have shown any morphological changes of
the lesion, and the patient is well. CONCLUSION: To the best of our knowledge, we
report the first case of an oncocytoma in a renal allograft complicating a
deceased-donor kidney transplant, which was successfully managed by active
surveillance.
PMID- 29966525
TI - Correction to: Identification of the functional role of peroxiredoxin 6 in the
progression of breast cancer.
AB - After the publication of this work [1] an error in Fig. 1c was brought to our
attention: the Western blots for PRDX6 and beta-actin were similar to those shown
in lanes 5-6 of Fig. 4g. To verify these findings, we have repeated this
experiment and the results are shown in a new Fig. 1c below. The repeated
experimental results are consistent with the previously reported findings in the
original study [1] and the functional role for PRDX6 in malignant progression of
human cancer including breast cancer has been widely documented and recognized in
numerous other studies [2]. We apologize for the error. However, this correction
does not affect the conclusions of the article.
PMID- 29966526
TI - Outcomes of esophagectomy after chemotherapy with biweekly docetaxel plus
cisplatin and fluorouracil for advanced esophageal cancer: a retrospective cohort
analysis.
AB - BACKGROUND: Docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy can cause
severe adverse events, including neutropenia and febrile neutropenia. The
feasibility of DCF therapy is a concern, particularly for elderly patients,
patients with moderate organ disorders, and patients suffering from malnutrition
caused by dysphagia or insufficient oral intake. We introduced a biweekly DCF
therapy (bDCF) for the purpose of reducing severe adverse events for these
fragile patients. This study investigated the feasibility and outcome of an
esophagectomy after bDCF therapy for patients with advanced esophageal squamous
cell carcinoma. METHODS: Fifty-nine patients with esophageal carcinoma underwent
an esophagectomy after DCF or bDCF therapy as primary chemotherapy. DCF was
administered to 37 patients in the DCF group, whereas bDCF was administered to 22
patients in the bDCF group. RESULTS: Patients in the bDCF group were
significantly older than those in the DCF group (p = 0.016). Heart and pulmonary
comorbidities were significantly more common in the bDCF than in the DCF group (p
< 0.001 and p = 0.039, respectively). Grade 3 or 4 neutropenia was less frequent
in the bDCF than in the DCF group (40.9 vs. 81.1%, p = 0.002). Anorexia was more
frequent in the DCF group than in the bDCF group (18.9 vs. 0%, p = 0.030). The
clinical response rate of the bDCF group was significantly higher than that of
the DCF group (86.4 vs. 62.2%, p = 0.047). There was no significant between-group
difference in the postoperative morbidity rate (bDCF 45.5% vs. DCF 32.4%) or in
the histological therapeutic effect. CONCLUSION: The results demonstrate that
primary bDCF therapy for high-risk patients with advanced esophageal cancer is
feasible and safe in both chemotherapeutic and perioperative periods without a
reduction in the efficacy of DCF therapy.
PMID- 29966527
TI - Dynamic bimodal changes in CpG and non-CpG methylation genome-wide upon CGGBP1
loss-of-function.
AB - OBJECTIVES: Although CpG methylation is well studied, mechanisms of non-CpG
methylation in mammals remains elusive. Studying proteins with non-CpG cytosine
methylation-sensitive DNA-binding, such as human CGGBP1, can unveil cytosine
methylation regulatory mechanisms. Here we have resequenced a published genome
wide bisulfite sequencing library and analyzed it at base level resolution. CpG,
CHG and CHH (where H is any nucleotide other than G) methylation states in non
targeting or CGGBP1-targeting shmiR lentivirus-transduced cells have been
analyzed to identify how CGGBP1 regulates CpG and non-CpG methylation. RESULTS:
We report that CGGBP1 acts as a dynamic bimodal balancer of methylation. Both
gain and loss of methylation observed upon CGGBP1 depletion were spatially
overlapping at annotated functional regions and not identifiable with any
sequence motifs but clearly associated with GC-skew. CGGBP1 depletion caused
clustered methylation changes in cis, upstream of R-loop forming promoters. This
was complemented by clustered occurrences of methylation changes in proximity of
transcription start sites of known cytosine methylation regulatory genes, altered
expression of which can regulate cytosine methylation in trans. Despite low
coverage, our data provide reliable estimates of the spectrum of methylation
changes regulated by CGGBP1 in all cytosine contexts genome-wide through a
combination of cis and trans-acting mechanisms.
PMID- 29966528
TI - Sub-acute intestinal obstruction - a rare complication of Plasmodium falciparum
malaria in an adult: a case report.
AB - BACKGROUND: Malaria remains a major public health problem in most tropical
countries. It occasionally presents with both typical and atypical signs and
symptoms. Gastrointestinal manifestations are common in malaria endemic areas but
intestinal obstruction as a complication is extremely rare. CASE PRESENTATION: We
present the case of a 42-year-old black African man who presented with signs and
symptoms of intestinal obstruction and was diagnosed as having Plasmodium
falciparum malaria. He was successfully treated with both parenteral and orally
administered antimalarial medication and the intestinal obstruction subsequently
resolved. CONCLUSION: With intestinal obstruction being an important cause of
morbidity and mortality, we report this case to highlight this rare complication
of malaria and therefore increase physicians' awareness and prompt diagnosis and
management.
PMID- 29966529
TI - Migraine-related disability and co-morbid depression among migraineurs in
Ethiopia: a cross-sectional study.
AB - BACKGROUND: Migraine headache is a neurologic disorder which mainly affects
younger and productive segment of population. Migraine not only causes pain; but
also affects quality of life in terms of low productivity and economic loss. The
main aim of this study was to examine migraine-related disability, co-morbid
depression, and relationship between the two. METHODS: A cross-sectional study
was conducted among migraineurs who visited two neurology referral clinics. The
study was conducted between June 1st 2016 to December 30th2016. Migraine
disability assessment score [MIDAS] and patient health questionnaire [PHQ-9] were
used to assess disability and depression, respectively. RESULTS: A total of 70
patients participated in the study. Fifty-three (74.3%) of our study participants
were women. Fifty one (72.9%) study participants were between age group 20-40
years. Migraine without aura was the most common subtype (70%); migraine with
aura accounted for the other 28.6%. The mean (+/- SD) headache frequency and
intensity was 23.4 +/- 14.9 days and 7.4 +/- 1.2 respectively. Major depressive
disorder was common in this group (41.4%). The mean MIDAS and PHQ-9 scores were
46.7 +/- 30 and 9.2 +/- 4.4 respectively. More than two-thirds (74.3%) of our
participants had severe disability. We found a statistically significant
correlation between migraine-related disability and co morbid depression among
our participants(r = 0.318, p-value = 0.007). CONCLUSION: The positive
correlation observed between migraine-related disability and co-morbid depression
warrant routine screening and treatment of disability and depression in
migraineurs; In addition, the observed high degree of disability among our
participants may indicate sub optimal treatment of these patients.
PMID- 29966530
TI - Priority-setting in health research in Iran: a qualitative study on barriers and
facilitators.
AB - BACKGROUND: Priority-setting is a complicated and time-consuming process;
however, if appropriately conducted, it could efficiently divert resources to the
most important studies. A considerable body of evidence indicates that priority
setting measures in health research taken so far in Iran have not satisfied
decision-makers, policy-makers, funders, communities, or even researchers. This
study was designed to explore the flaws of these measures and their deciding
factors. METHODS: We conducted semi-structured interviews with 23 key
participants and used a thematic data-analysis approach to analyse verbatim
transcripts and documents. Our interviewees, who were skilful at conducting
health research and worked as managers at different levels of the health system,
were selected using a purposeful sampling. We asked about their experiences of
priority-setting in health and relevant challenges and asked for recommendations.
These semi-structured interviews were taped, transcribed and analysed in terms of
content and themes using the MAXQDA10 qualitative data-analysis software.
RESULTS: With regard to priority-setting facilitators and barriers, four themes
were extracted, namely managerial factors, structural factors, motivational
factors, and process factors. Managers' commitment, consideration of intellectual
property, compliance with superordinate rules, and provision of a definition of
reliable criteria were among the facilitators. The rapid turnover of managers,
inefficiency of criteria for faculty promotion, and disregard of appeal
mechanisms were examples of the barriers. CONCLUSION: It is important to consider
appropriate regulations and motivations to provide research priorities and divert
scarce resources to them. In addition, it is necessary to improve the knowledge
and skills of researchers and research administration offices on priority-setting
methods, thereby enhancing priority-oriented research projects.
PMID- 29966531
TI - Inhibition of the hepatic Nlrp3 protects dopaminergic neurons via attenuating
systemic inflammation in a MPTP/p mouse model of Parkinson's disease.
AB - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with
progressive loss of dopaminergic (DA) neurons. Systemic inflammation is shown to
initiate and exacerbate DA neuronal degeneration in the substantia nigra. The
infiltration and transformation of immune cells from the peripheral tissues are
detected in and around the affected brain regions of PD patients. Our previous
studies demonstrated the crucial role that microglial Nod-like receptor protein
(NLRP) 3 inflammasome plays in the pathogenesis of PD. Nevertheless, the direct
linkage between peripheral inflammation and DA neuron death remains obscure.
METHODS: In the present study, we detected the NLRP3 expressions in the midbrain,
liver, and bone marrow-derived macrophages in response to 1-methyl-4-phenyl-1, 2,
3, 6-tetrahydropyridine (MPTP) acute and chronic challenge. We then used a tail
vein injection of Nlrp3-siRNA wrapped with lentivirus to explore the potential
influence of hepatic NLRP3 inflammasome-mediated inflammation on neuronal injury
in a mouse model of PD via immunohistochemistry, ELISA, and Western blotting
analysis. RESULTS: We showed that siNlrp3 downregulated the NLRP3 protein
expression and inhibited the activation of NLRP3 inflammasomes in mice livers.
The tail vein injection of LV3-siNlrp3 reduced the liver pro-inflammatory
cytokine production, which subsequently alleviated MPTP-triggered microglial
activation and DA neuron loss in the midbrain. These findings indicated that
inhibition of hepatic NLRP3 inflammasome weakens inflammatory cytokines spreading
into the brain and delays the progress of neuroinflammation and DA neuronal
degeneration. CONCLUSION: This study gives us an insight into the direct linkage
between liver inflammation and DA neuron damage in the pathogenesis of PD and
provides the potential target of NLRP3 for developing novel drugs for PD therapy.
PMID- 29966532
TI - Circadian rhythms of migraine attacks in episodic and chronic patients: a cross
sectional study in a headache center population.
AB - BACKGROUND: Migraine is considered a disease with diurnal and 24 h pattern,
though the existence of a prevalent circadian rhythm associated to migraine
frequency and severity is still not clear. This observational cross-sectional
study aimed to: 1. Assess the circadian rhythm of migraine attacks onset in a
large patients' population selected in a headache center and including episodic
and chronic migraine 2. Analyze the principal characteristic of the different
onset time groups 3. Verify if migraine features, particularly those associated
to chronic and disabling migraine, could be discriminant factors for time of
onset group. METHODS: We selected 786 consecutive migraine outpatients, who
correctly completed the headache diaries for 3 consecutive months and who
fulfilled the diagnosis of migraine without aura-MO, migraine with typical aura
alone or associated to migraine without aura - MO/MA and chronic migraine - CM.
For the time of headache onset, we considered four time slots, from 6 to 12 am
(morning), from 1 to 6 pm (afternoon), from 7 to 11 pm (evening), from 12 pm to 5
am (night), and an additional category named "any time". Each time slot included
the 60 min preceding the next one (e.g. an onset at 12.30 am was included in 6-12
am time slot). We evaluated in all patients the pericranial tenderness, anxiety
and depression tracts, headache-related disability, sleep features, quality of
life, allodynia and fatigue. RESULTS: We scored a total of 16,578 attacks,
distributed in the entire day. The most of patients, including CM, satisfied the
criteria for the "any time" onset. Night onset was significantly less represented
in the MA/MO group. Patients with prevalent night onset were significantly older,
with longer migraine history and shorter sleep duration. Age and illness duration
were the variables discriminating the different onset time groups. CONCLUSIONS:
The most of migraine patients do not report a specific circadian profile of
attacks occurrence. Frequent migraine, severe disability, psychopathological
tracts as well as central sensitization signs, do not match with a specific
circadian rhythm of attacks onset. Night onset migraine seems to be an age
related feature, emerging in the course of the disease.
PMID- 29966533
TI - Genomic characterization of colitis-associated colorectal cancer.
AB - BACKGROUND: Inflammatory bowel disease (IBD), which includes ulcerative colitis
(UC) and Crohn's disease (CD), is a chronic, idiopathic, repeated inflammatory
disease. Colorectal cancer (CRC) that develops in patients with IBD is known as
colitis-associated colorectal cancer (CAC), but the underlying carcinogenic
mechanism remains unclear. Genomic analysis of sporadic CRC has been well
described based on next-generation sequencing (NGS) data. Using NGS, we compared
all exons of 415 cancer-associated genes in patients in Japan and the USA who had
CRC and found similar genomic alteration patterns among the two populations.
However, genomic analysis of CAC has not been thoroughly investigated. MAIN BODY:
The molecular pathogenesis of CAC shares many features with sporadic CRC, but
there are distinct variations in the time and frequency of some alterations. Gene
alterations in CAC are gradually being elucidated using genomic sequencing
analyses. Some studies have shown that gene alteration patterns differ between UC
and CD. The carcinogenesis of CAC depends on unique environmental, genetic, and
immunological factors. CONCLUSIONS: In this review, we have discussed the
differences in genomic alterations between sporadic CRC and CAC. NGS in patients
with IBD has the potential to detect early CAC and to suggest therapeutic
targets.
PMID- 29966534
TI - Glycemic dysregulation in a patient with type 2 diabetes treated with 5
azacitidine: a case report.
AB - BACKGROUND: Diabetes and myelodysplastic syndrome are two conditions that may
coexist in a single patient, since both diseases are prevalent in the elderly.
The pathophysiology of myelodysplastic syndrome involves recurrent genetic
mutations, especially in genes controlling epigenetic regulation. Although the
pathophysiology of diabetes is not well understood, several studies suggest a
role of epigenetics in type 2 diabetes. CASE PRESENTATION: We report here for the
first time the case of a 75-year-old Caucasian man who was treated for both
diabetes and acute myeloid leukemia secondary to myelodysplastic syndrome, with a
temporal association between glycemic dysregulation and the intake of 5
azacitidine. In fact, 2-3 days after starting each 7-day cycle of 5-azacitidine,
he reported higher blood glucose levels, requiring an increased dose of self
administered insulin. CONCLUSION: This observation could help to understand the
pathophysiology of these two conditions and could encourage physicians to monitor
blood glucose levels in patients under hypomethylating agent with a history of
diabetes.
PMID- 29966536
TI - A novel miRNA, miR-13664, targets CpCYP314A1 to regulate deltamethrin resistance
in Culex pipiens pallens.
AB - Extensive insecticide use has led to the resistance of mosquitoes to these
insecticides, posing a major barrier to mosquito control. Previous Solexa high
throughput sequencing of Culex pipiens pallens in the laboratory has revealed
that the abundance of a novel microRNA (miRNA), miR-13664, was higher in a
deltamethrin-sensitive (DS) strain than a deltamethrin-resistant (DR) strain.
Real-time quantitative PCR revealed that the miR-13664 transcript level was lower
in the DR strain than in the DS strain. MiR-13664 oversupply in the DR strain
increased the susceptibility of these mosquitoes to deltamethrin, whereas
inhibition of miR-13664 made the DS strain more resistant to deltamethrin.
Results of bioinformatic analysis, quantitative reverse-transcriptase polymerase
chain reaction, luciferase assay and miR mimic/inhibitor microinjection revealed
CpCYP314A1 to be a target of miR-13664. In addition, downregulation of CpCYP314A1
expression in the DR strain reduced the resistance of mosquitoes to deltamethrin.
Taken together, our results indicate that miR-13664 could regulate deltamethrin
resistance by interacting with CpCYP314A1, providing new insights into mosquito
resistance mechanisms.
PMID- 29966535
TI - Is onchocerciasis elimination in Africa feasible by 2025: a perspective based on
lessons learnt from the African control programmes.
AB - BACKGROUND: Onchocerciasis is found predominantly in Africa where large scale
vector control started in 1974. Registration and donation of ivermectin by Merck
& Co in 1987 enabled mass treatment with ivermectin in all endemic countries in
Africa and the Americas. Although elimination of onchocerciasis with ivermectin
was considered feasible only in the Americas, recently it has been shown possible
in Africa too, necessitating fundamental changes in technical and operational
approaches and procedures. MAIN BODY: The American programme(OEPA) operating in
onchocerciasis epidemiological settings similar to the mild end of the complex
epidemiology of onchocerciasis in Africa, has succeeded in eliminating
onchocerciasis from 4 of its 6 endemic countries. This was achieved through
biannual mass treatment with ivermectin of 85% of the eligible population, and
monitoring and evaluation using serological tests in children and entomological
tests. The first African programme(OCP) had a head start of nearly two decades.
It employed vector control and accumulated lots of knowledge on the dynamics of
onchocerciasis elimination over a wide range of epidemiological settings in the
vast expanse of its core area. OCP made extensive use of modelling and
operationalised elimination indicators for entomological evaluation and
epidemiological evaluation using skin snip procedures. The successor African
programme(APOC) employed mainly ivermectin treatment. Initially its objective was
to control onchocerciasis as a public health problem but that objective was later
expanded to include the elimination of onchocerciasis where feasible. Building on
the experience with onchocerciasis elimination of the OCP, APOC has leveraged
OCP's vast modelling experience and has developed operational procedures and
indicators for evaluating progress towards elimination and stopping ivermectin
mass treatment of onchocerciasis in the complex African setting. CONCLUSIONS:
Following the closure of APOC in 2015, implementation of onchocerciasis
elimination in Africa appears to overlook all the experience that has been
accumulated by the African programmes. It is employing predominantly American
processes that were developed in a dissimilar setting from the complex African
onchocerciasis setting. This is impeding progress towards decisions to stop
intervention in many areas that have reached the elimination point. This article
summarizes lessons learned in Africa and their importance for achieving
elimination in Africa by 2025.
PMID- 29966537
TI - Oviposition strategy for superparasitism in the gregarious parasitoid Oomyzus
sokolowskii (Hymenoptera: Eulophidae).
AB - Superparasitism is an adaptive strategy in solitary parasitoids, yet insufficient
evidence confirms this in gregarious ones. We here ask whether the gregarious
parasitoid Oomyzus sokolowskii is able to discriminate in attack and progeny
allocation between parasitized and unparasitized Plutella xylostella larvae, and
how the parasitoid allocates brood size and sex to superparasitized hosts due to
some circumstances. We found that female parasitoids preferred unparasitized to
parasitized host larvae, and allocated a smaller brood with more males in the
later than in the former host. Brood size and sex ratio decreased from
superparasitized hosts with a 48 h interval since a previous attack compared with
one without an interval; they also declined from the host superparasitized by the
parasitoid with oviposition experience compared with one without it. Brood size
and sex ratio did not differ between the host superparasitized by the same
parasitoid as in the first attack and that by a different one. Our findings
suggest that O. sokolowskii females may adjust their oviposition decisions on
progeny allocation in response to parasitized P. xylostella larvae to maximize
their fitness gains from superparasitism.
PMID- 29966538
TI - Loss of follow-up in transition to adult CHD: a single-centre experience.
AB - Lapses in care during transition in adult CHD patients lead to increased
morbidity and mortality. Previous studies have investigated predictors of poor
follow-up in universal healthcare paradigms and select American populations. We
studied patients with a wide spectrum of CHD severity within a single American
centre to identify factors associated with successful internal transition and
maintenance of care. Loss of follow-up was defined as no documented cardiac
follow-up for ?3 years. Ambulatory cardiology patients aged 16-17 years with CHD
were retrospectively enrolled and contacted. A survey assessing demographics,
patients' understanding of their CHD, medical status, and barriers to care was
administered. On the basis of chart review of 197 enrolled patients, 74
demonstrated loss of follow-up (37.6%). Of 78 successfully contacted patients, 58
were surveyed, of whom a minority had loss of follow-up (n=16). The status of
most patients with loss of follow-up was not known. Maintenance of care was
associated with greater complexity of CHD (p<0.01), establishment of care with an
adult CHD provider (p<0.001), use of prescription medications (p<0.001), and
receipt of education emphasising the importance of long-term cardiac care
(p<0.003). Insurance lapses were not associated with loss of follow-up (p=0.08).
Transition and maintenance of care was suboptimal even within a single centre.
Over one-third of patients did not maintain care. Patients with greater
complexity CHD, need for medications, receipt of transition education, and care
provided by adult CHD providers had superior follow-up.
PMID- 29966539
TI - Automated Fall Detection Technology in Inpatient Geriatric Psychiatry: Nurses'
Perceptions and Lessons Learned.
AB - ABSTRACTHospitalized older adults are at high risk of falling. The HELPER system
is a ceiling-mounted fall detection system that sends an alert to a smartphone
when a fall is detected. This article describes the performance of the HELPER
system, which was pilot tested in a geriatric mental health hospital. The
system's accuracy in detecting falls was measured against the hospital records
documenting falls. Following the pilot test, nurses were interviewed regarding
their perceptions of this technology. In this study, the HELPER system missed one
documented fall but detected four falls that were not documented. Although
sensitivity (.80) of the system was high, numerous false alarms brought down
positive predictive value (.01). Interviews with nurses provided valuable
insights based on the operation of the technology in a real environment; these
and other lessons learned will be particularly valuable to engineers developing
this and other health and social care technologies.
PMID- 29966540
TI - Challenges in identifying Candida auris in hospital clinical laboratories: a need
for hospital and public health laboratory collaboration in rapid identification
of an emerging pathogen.
PMID- 29966541
TI - Ultrasound-Assisted Ionic Liquid-Dispersive Liquid-Liquid of Curcumin in Food
Samples Microextraction and Its Spectrophotometric Determination.
AB - Background: A rapid and new ultrasound-assisted ionic liquid-dispersive liquid
liquid microextraction method (UA-IL-DLLME) was presented for the determination
of curcumin by spectrophotometry. Objective: To determine trace levels of
curcumin in food samples by using green and low-cost method development. Methods:
1-Butyl-3-methylimidazolium hexafluorophosphate was used to extract curcumin from
sample solutions with the aid of sonication. Optimum extraction efficiency was
determined by examining extraction solvents, pH, centrifugation speed, time,
sonication period, and temperature. The influences of diverse ions on the
recovery of curcumin were examined. The concentration of curcumin in the final
solution was measured by spectrophotometer at 425 nm. Results: The enrichment
factor achieved was 167. The LOD and the RSD were 0.51 MUg/L and 4.3%,
respectively. The presented method was performed to detect curcumin in 20 food
samples. Conclusions: The presented UA-IL-DLLME method is simple, low in cost,
environmentally friendly, rapid, and sensitive and requires minimal use of toxic
organic solvents. Highlights: A microextraction method was applied to increase
sensitivity. Higher enrichment factors and lower detection limits were observed.
The proposed technique is easy, cost-effective, accurate, and precise.
PMID- 29966543
TI - Erratum: E5 can be expressed in anal cancer and leads to epidermal growth factor
receptor-induced invasion in a human papillomavirus 16-transformed anal
epithelial cell line.
PMID- 29966544
TI - Behavioral Assessment of Vision in Pigs.
AB - Swine (Sus scrofa) are often the 'gold standard' laboratory animal for
ophthalmology research due to the anatomic and physiologic similarities between
the porcine and human eye and retina. Despite the importance of this model, few
tools for behavioral vision assessment in pigs are available. The aim of this
study was to identify and validate a feasible and reproducible behavioral test to
assess vision in a pig model of photoreceptor degeneration. In addition, a robust
behavioral test will reduce stress and enhance enrichment by allowing animals
opportunities for environmental exploration and by reducing the number of
invasive experimental procedures. Two distinct behavioral approaches were tested:
the obstacle-course test and temperament test. In the obstacle-course test, pigs
were challenged (after an initial training period) to navigate a 10-object
obstacle course; time and the number of collisions with the objects were
recorded. In the temperament test, the time needed for pigs to complete 3
different tasks (human-approach, novel-object, and open-door tests) was recorded.
The obstacle-course test revealed significant differences in time and number of
collisions between swine with vision impairment and control animals, and the
training period proved to be pivotal to avoid bias due to individual animal
characteristics. In contrast, the temperament test was not altered by vision
impairment but was validated to measure stress and behavioral alterations in
laboratory pigs undergoing experimental procedures, thus achieving marked
refinement of the study.
PMID- 29966545
TI - Rapid Detection of Listeria in Ice Cream in 13 Hours Using the Roka Listeria
Detection Assay.
AB - Background: Listeria contamination is a major concern in the ice cream industry;
therefore, early and accurate detection is vital. Current detection methods
require about a 24 h enrichment period for detection. Objective: Enhance the
early detection of Listeria in ice cream using the highly sensitive isothermal
ribosomal RNA-based Roka/Atlas Listeria Detection Assay. Methods: The R2 Medium
was developed for Listeria enrichment by Molecular Epidemiology, Inc. (Seattle,
WA). Comparative growth curve studies were performed on the new R2 Medium for
Listeria and the currently validated media for the Roka Listeria Detection Assay.
Subsequently, a method comparison between the Roka Listeria Detection Assay and
the U.S. Food and Drug Administration's (FDA) Bacteriological Analytical Manual
(BAM) Chapter 10 reference method on ice cream was carried out. Results: The R2
Medium supports the growth of L. monocytogenes better than Buffered Listeria
Enrichment Broth, Demi-Fraser broth, and Modified University of Vermont Broth, as
indicated by the faster growth rate of the organism. When used as an enrichment
medium in a method comparison study of ice cream, the results showed that R2
Medium-enriched samples tested with the Roka Listeria Detection Assay gave an
equivalent performance compared with the 24 h FDA-BAM reference method at 10 and
18 h post-enrichment for Listeria. Conclusions: The results from this study
indicate that the new R2 Medium and the highly sensitive Roka Listeria Detection
Assay allowed for the rapid detection of Listeria species in ice cream in 13 h.
Highlights: The Roka Listeria Detection Assay, in conjunction with a new media
formulation (R2 Medium), allowed for the early detection of Listeria in ice cream
and may be applied in other food matrixes and environmental samples.
PMID- 29966549
TI - Corrigendum: ICTV Virus Taxonomy Profile: Ophioviridae.
PMID- 29966557
TI - Narcotic-Dependent Patients Derive Equal Benefit from Enhanced Recovery.
AB - Areas of the southeast United States have endemic levels of prescription drug
use, diversion, and abuse. Because preoperative narcotics use is associated with
increased surgical morbidity and increased readmission rates, there is a
compelling need to categorize health outcomes of patients maintaining an active
opioid prescription. The purpose of this study is to determine the health
outcomes of preoperative narcotic users who undergo colorectal surgery within the
enhanced recovery (ER) protocol, a set of multimodal interventions designed to
reduce postoperative complications. Five hundred and five colorectal surgery
patients were identified within the ER protocol at Carilion Clinic. Opioid
dependence was defined as an active prescription for 30 days before surgery.
Thirty-day outcome variables were defined by the National Surgical Quality
Improvement Program. One hundred and one patients were identified as opioid
dependent and 404 as opioid naive. Groups were comparable in terms of age at
surgery, mean body mass index, and presurgical physical classification. Groups
fared similarly with regard to readmission (chi2, P > 0.999), reoperation (chi2,
P = 0.869), and average length of stay [t(135) = 1.49, P = 0.137]. These
preliminary data show that opioid-dependent patients derive benefit equal to
opioid-naive patients within the ER protocol.
PMID- 29966558
TI - Outcome and Cost Analysis of Hand-Sewn and Stapled Anastomoses in the Reversal of
Loop Ileostomy.
AB - Diverting loop ileostomies are common procedures for protecting high-risk
anastomoses. There is little consensus on the most ideal technique both in terms
of cost efficiency and outcome. Data for this study were collected from 101
patients who underwent loop ileostomy reversal between 2009 and 2014 at
Morristown Medical Center. Of the 101 patients included in the review, 57
received a hand-sewn anastomosis (HS-A) and 44 received a stapled anastomosis (S
A). Average total hospital charges for stapled anastomoses were significantly
greater than that for hand-sewn anastomoses, as were total operating room supply
costs. When the total cost of the operation itself was considered, S-A cases were
still found to be significantly greater than HS-A cases. Hospital room charges,
total lab charges, pathology charges, and EKG/ECG charges were all greater for S
A cases than HS-A cases. Overall costs were greater for S-As than hand-sewn
anastomoses and because of a lack of difference in procedure length, stapler
supply costs were not offset. Complication rates and length of stay were also
similar between the techniques. We found S-A cases to be more costly and have a
greater cost/hour than HS-A cases.
PMID- 29966559
TI - Understanding Disparities in Breast Cancer Care in Memphis, Tennessee.
AB - Although significant progress has been made in improving breast cancer survival,
disparities among racial, ethnic, and underserved groups still exist. The goal of
this investigation is to quantify racial disparities in the context of breast
cancer care, examining the outcomes of recurrence and mortality in the city of
Memphis. Patients with a biopsy-proven diagnosis of breast cancer from January 1,
2002, through December 31, 2012, were obtained from the tumor registry. Black
patients were more likely to have advanced (II, III, or IV) clinical stage of
breast cancer at diagnosis versus white patients. Black breast cancer patients
had a two times higher odds of recurrence (95% confidence interval: 1.4, 3.0)
after adjusting for race and clinical stage. Black breast cancer patients were
1.5 times more likely to die (95% confidence interval: 1.2, 1.8), after adjusting
for race; age at diagnosis; clinical stage; ER, PR, HER2 status; and recurrence.
Black women with stages 0, I, II, and III breast cancer all had a statistically
significant longer median time from diagnosis to surgery than white women. Black
patients were more likely to have advanced clinical stages of breast cancer at
diagnosis versus white patients on a citywide level in Memphis. Black breast
cancer patients have higher odds of recurrence and mortality when compared with
white breast cancer patients, after adjusting for appropriate demographic and
clinical attributes. More work is needed to develop, evaluate, and disseminate
interventions to decrease inequities in timeliness of care for breast cancer
patients.
PMID- 29966560
TI - Frailty Predicts Morbidity and Mortality after Colectomy for Clostridium
difficile Colitis.
AB - Frailty has been noted as a powerful predictive preoperative tool for 30-day
postoperative complications. We sought to evaluate the association between
frailty and postoperative outcomes after colectomy for Clostridium difficile
colitis. The National Surgical Quality and Improvement Program cross
institutional database was used for this study. Data from 470 patients with a
diagnosis of C. difficile colitis were used in the study. Modified frailty index
(mFI) is a previously described and validated 11-variable frailty measure used
with the National Surgical Quality and Improvement Program to assess frailty.
Outcome measures included serious morbidity, overall morbidity, and Clavien IV
(requiring ICU) and Clavien V (mortality) complications. The median age was 70
years and body mass index was 26.9 kg/m2. 55.6 per cent of patients were females.
98.5 per cent of patients were assigned American Society of Anesthesiologists
Class III or higher. The median mFI was 0.27 (0-0.63). Because mFI increased from
0 (non-frail) to 0.55 and above, the overall morbidity increased from 53.3 per
cent to 84.4 per cent and serious morbidity increased from 43.3 per cent to 78.1
per cent. The Clavien IV complication rate increased from 30.0 per cent to 75.0
per cent. The mortality rate increased from 6.7 per cent to 56.2 per cent. On a
multivariate analysis, mFI was an independent predictor of overall morbidity
(AOR: 13.0; P < 0.05), mortality (AOR: 8.8; P = 0.018), cardiopulmonary
complications (AOR: 6.8; P = 0.026), and prolonged length of hospital stay (AOR:
6.6; P = 0.045). Frailty is associated with increased risk of complications in C.
difficile colitis patients undergoing colectomy. mFI is an easy-to-use tool and
can play an important role in the risk stratification of these patients who
generally have significant morbidity and mortality to begin with.
PMID- 29966561
TI - Biomechanical Comparison of Fibrin Sealants for Mesh Fixation.
AB - Adhesive use for fixation in hernia repair allows for complete and immediate mesh
surface area adherence. Little is known about the fixation strengths of the
products and application methods available. The purpose of this study was to
compare the immediate and early strength of fixation of TisseelTM and EvicelTM
using hand and spray application techniques. Sixteen Mongrel swine underwent
implantation of large-pore, mid-weight polypropylene mesh fixated with either
TisseelTM or EvicelTM, applied by hand or with a spray apparatus. Time points
studied were zero and four days. All samples underwent lap shear testing to
quantify the strength of the mesh-tissue interface as an indicator of mesh
fixation strength. Thirty Day 4 and 16 Day 0 samples were tested. Manually
applied TisseelTM mean fixation strength was 2.05 N/cm at Day 0 and 6.02 N/cm at
Day 4. Sprayed TisseelTM had mean fixation strength of 1.22 N/cm at Day 0 and
7.21 N/cm at Day 4. Manually applied EvicelTM showed mean fixation strength of
0.92 N/cm at Day 0 and 6.73 N/cm at Day 4. Mean fixation strength of sprayed
EvicelTM was 0.72 N/cm at Day 0 and 6.70 N/cm at Day 4. Analysis of variance
showed no difference between groups at Day 0 or Day 4. Immediate strength of mesh
fixation could have significant implications for early recurrence and mesh
contraction. This study demonstrates that no difference exists in immediate or
early fixation strength between these two brands of sealants or their method of
application.
PMID- 29966562
TI - Too Much of a Good Thing: Radioactive Iodine Ablation Use for Micropapillary
Thyroid Carcinoma.
AB - Radioactive iodine (RAI) is not routinely recommended for the adjuvant treatment
of micropapillary thyroid carcinoma (MPTC). We aimed to report on clinical and
pathologic factors associated with the use of RAI in these patients. We queried
the Surveillance, Epidemiology, and End Results database for patients who
underwent surgery for MPTC (tumor size <=1 cm) from 1988 to 2009. We excluded
patients without a biopsy-proven diagnosis, those diagnosed at autopsy, and
patients with documented extra-thyroidal extension. Multivariate logistic
regression models predicted the use of RAI based on patient, tumor, and treatment
related factors. We identified 24,076 patients with MPTC that were eligible for
study inclusion. Of these, 6,172 (25.6%) received RAI. Lymph node metastases were
present in 23.8 per cent of those for whom lymph node status was known. On
multivariate analysis, an increasing number of positive nodes, increasing tumor
size, Asian race, and male gender predicted the use of RAI. RAI use was less
likely in those with advancing age, an increasing number of lymph nodes examined
and patients that received less than a total thyroidectomy. Among node-negative
patients, Asian race and increasing tumor size predicted the use of RAI. Factors
predicting decreased use of RAI were an increasing number of lymph nodes
examined, unknown race, less than a total thyroidectomy, and advancing age. A
significant number of MPTC patients receive potentially unnecessary RAI.
PMID- 29966563
TI - What Is Most Important to the Endoscopist for Therapeutic Plan? Morphology versus
Pathology: A Nationwide Multicenter Retrospective Study in Korea.
AB - Histologic discrepancy may sometimes occur between biopsy and endoscopic
resection. We investigated the discrepancy rate between the biopsy and the
resection lesion in the Korean population. From January 2010 to October 2016, 268
patients with gastric endoscopic mucosal resection/endoscopic submucosal
dissection history from nationwide hospitals were enrolled retrospectively. We
compared the histologic discrepancy rates from the biopsy and the resection. The
mean age was 63.2 years. Gastric adenomas occurred most frequently in the antrum.
The pathology of the resected specimens classified 25 lesions (9.3%) as
gastritis/hyperplasia, 146 lesions (54.5%) as low-grade dysplasia, 76 lesions
(28.4%) as high-grade dysplasia (HGD), and 21 lesions (7.8%) as adenocarcinoma.
The discrepancy rate between biopsy and resection was 23.1 per cent. Among the 44
cases of gastritis/hyperplasia, two cases (4.5%) were diagnosed as HGD and 11
cases (25.0%) were diagnosed as cancer after resection. Among the 182 cases of
low-grade dysplasia, 33 cases (18.1%) were diagnosed as HGD and nine cases (5.0%)
were diagnosed as cancer after resection. Gastritis/hyperplasia, ulceration, and
lesions in the lower body location were significant factors related to the
discrepancies. Especially, discrepancy occurred most frequently in
gastritis/hyperplasia lesions with ulcer in the lower body. There was
considerable histologic discrepancy between biopsy and resection. Ulcerative-type
tumor morphology and biopsy diagnosis of gastritis/hyperplasia are suggestive
factors predictive of discrepancy between biopsy and resection in terms of
malignancy. Therefore, although the results of biopsy are gastritis/hyperplasia,
suspicious tumorous lesions with ulcer should be indicative of active endoscopic
resection for diagnosis and treatment.
PMID- 29966564
TI - Mild Traumatic Brain Injuries Can Be Safely Managed without Neurosurgical
Consultation: The End of a Neurosurgical "Nonsult".
AB - In 2010, 2.5 million people sustained a traumatic brain injury (TBI), with an
estimated 75 per cent being mild TBI. Mild TBI is defined as a Glasgow Coma Scale
(GCS) of 13 to 15. Based on recent data and our institutional experience, we
hypothesized that mild TBI patients, including patients on aspirin, could be
safely managed by trauma surgeons without neurosurgical consultation. Trauma
patients admitted to a single Level I trauma center from June 2014 through July
2015 aged 18 years or older were evaluated. Patients with a GCS >=14, regardless
of intoxication, with an epidural or subdural hematoma <=4 mm, trace or small
subarachnoid hemorrhage, and/or nondisplaced skull fracture were prospectively
enrolled. The primary outcomes were needed for neurosurgical consultation and
intervention. Secondary outcomes included readmission rate and neurologic
morbidity and mortality rate. Of 1341 trauma admits, 77 were enrolled. No
patients required neurosurgical intervention. Only 1/75 (1.3%) patients required
neurosurgical consultation. Outpatient follow-up was achieved with 75/77 (97.4%)
patients. No mortalities, major neurologic morbidities, or readmissions were
observed (95% confidence interval 0-4%). None of the 21 patients on aspirin
required neurosurgical intervention and only 1/21 (4.8%) patients required
neurosurgical consultation with no mortalities observed at follow-up. Management
of mild TBI can be safely accomplished by trauma surgeons without routine
neurosurgical consultation. Larger multicenter prospective studies are required
to evaluate our finding that this also may be safe in patients taking aspirin.
PMID- 29966565
TI - Early Urinary Dysfunction after Laparoscopic Rectal Cancer Surgery: Does
Surgeons' Learning Curve Matter?
AB - Poor early urinary outcomes after laparoscopy were reported in studies comparing
laparoscopic versus open rectal cancer surgery. One possible explanation was that
these studies might include a number of patients on the laparoscopic surgeons'
learning curve. This study aims to evaluate whether the learning curve of
laparoscopic rectal cancer surgery influences early postoperative urinary
dysfunction. Between September 2009 and December 2014, 208 consecutive patients
undergoing laparoscopic rectal resection for rectal cancer were enrolled in the
present study. All the clinical data were obtained from a prospectively compiled
database. The primary outcomes were the incidences of postoperative urinary
retention (POUR) and major urinary dysfunction requiring long-term urinary
catheterization. POUR and major urinary dysfunction rate were 20.2 per cent
(42/208) and 4.3 per cent (9/208), respectively. The learning curve analysis for
operative time using the moving average method showed stabilization at 80 cases.
Surgeon experience was divided into two periods: learning curve period (1-80
cases) and experienced period (81-208 cases). Multivariate analysis showed that
older age (OR = 3.250, P = 0.006) and learning curve (OR = 2.241, P = 0.024) were
independent risk factors for POUR. Learning curve was not significantly
associated with increased rates of major urinary dysfunction (OR = 3.378, P =
0.092). Learning curve is a significant risk factor for increased rate of POUR
after laparoscopic rectal cancer surgery. Technical training may be key to
shorten the learning curve and limit its impact on the postoperative urinary
complications.
PMID- 29966566
TI - Role of Laparoscopic Surgery in the Current Management of Mirizzi Syndrome.
AB - Mirizzi syndrome (MS) is an uncommon complication of cholelithiasis caused by
extrinsic biliary compression by stones in the gallbladder infundibulum or cystic
duct. The purpose of this study was to evaluate the outcomes associated with a
laparoscopic approach to this disease process. This is a 10-year, retrospective
study conducted at two academic medical centers with established acute care
surgery practices. Patients with a diagnosis of MS confirmed intraoperatively
were included. Eighty-eight patients with MS were identified with 55 (62.5%)
being type 1. Twenty six (29.5%) patients, all type 1, underwent successful
laparoscopic cholecystectomy. Of the 62 patients that underwent open
cholecystectomy, 27.3 per cent had a laparoscopy converted to open procedure.
There was no significant difference in overall complications (19.2 vs 29%) among
those undergoing laparoscopic versus open cholecystectomy. Length of stay was
lower in patients that had a laparoscopic approach (P = 0.001). Laparoscopic
cholecystectomy can safely be attempted in type 1 MS and seems to be associated
with fewer overall complications and shorter length of stay compared with an open
approach.
PMID- 29966567
TI - Hospital-Based Study of Compliance with NCCN Guidelines and Predictive Factors of
Sentinel Lymph Node Biopsy in the Setting of Thin Melanoma Using the National
Cancer Database.
AB - Thin melanoma is the most common form of melanoma in the United States. The
National Comprehensive Cancer Network (NCCN) has guidelines for sentinel lymph
node biopsy (SLNB) which recommend "discuss and consider" SLNB for invasion >0.75
mm and "discuss and offer" SLNB for invasion >0.75 mm with suspicious features.
This study looked at compliance with NCCN guidelines and factors that are
predictive of a positive SLNB. This is a retrospective study of patients
diagnosed with thin melanoma 2012-2013 using the National Cancer Database. A
total of 26,456 patients met study qualifications. Univariate analysis showed
that 76 per cent of patients meeting criteria underwent SLNB. Patients
recommended to "discuss and consider" received SLNB 53 per cent of the time and
those not recommended for SLNB received SLNB 20 per cent of the time. On
multivariate analysis, depth was not predictive for positive SLNB whereas mitoses
and ulceration were. Other factors predictive of positive SLNB were nodular cell
type, lymphovascular invasion, and Clark's level greater than or equal to IV.
Patients with thin melanoma that meet NCCN guidelines for SLNB undergo this
procedure in good compliance but those who do not meet criteria continue to
receive SLNB. Positive predictive factors for positive SLNB include mitoses,
ulceration, Clark's level, and primary site.
PMID- 29966568
TI - Chest Wall Stabilization Leads to Shortened Chest Tube Stay Time in Rib Fracture
Patients after Traumatic Chest Wall Injury.
AB - Rib fixation has become a strategy for patients with displaced rib fractures and
hemo/pneumothoraces (HTX/PTX). Rib plating improves pain control and respiratory
mechanics, thereby reducing recovery times and morbidity/mortality. Current
treatment consists of chest tube placement, pain control, and pulmonary toilet.
The addition of rib plating should reduce time till HTX/PTX resolution and chest
tube removal. The study compares chest tube stay time in rib-plated patients with
those managed with current treatment. We hypothesize that patients undergoing rib
plating will have a reduction in chest tube stay times. A retrospective review of
a Level 1 trauma registry was performed. Rib-plated patients (n = 70) from 2013
to 2015 were compared with a randomly selected, nonoperative, injury-matched,
historical (2003-2008) control group (n = 60). Demographics were obtained.
Independent variables analyzed include Injury Severity Score (ISS), intensive
care unit days, length of stay, and chest tube stay times. 60 control patients
had an average ISS of 19 and age of 51 years, compared with ISS of 20 and age of
56 years in plated patients. Plated patients had a reduction in chest tube days,
6.5 versus 8.4 days, P value = 0.02. Plated patients had 14 intensive care unit
days versus 19 days, P value = 0.09. T tests were performed to confirm
significance. Reduction in chest tube days improves patient pain and allows for
improved ambulation and pulmonary toilet, helping reduce respiratory
complications. Our review shows that plating may prove beneficial in reducing
complications associated with management of HTX/PTX in the setting of rib
fractures.
PMID- 29966569
TI - Management of Esophageal Perforation: 28-Year Experience in a Major Referral
Center.
AB - Esophageal perforation constitutes a surgical emergency. Despite its gravity, no
single strategy has been described as sufficient to deal with most situations to
date. The aim of this study was to assess the etiology, management, and outcome
of esophageal perforation over a 28-year period, to characterize optimal
treatment options in this severe disease. A retrospective clinical review of all
patients treated for esophageal perforation at Ramon y Cajal Hospital between
January 1987 and December 2015 was performed (n = 57). Iatrogenic injury was the
most frequent cause of esophageal perforation (n = 32). Abdominal esophagus was
the main location (23 patients; 40.4%). Eight patients (14%) were managed with
antibiotics and parenteral nutrition. In seven patients (12.3%), an endoscopic
stent was implanted. Surgical therapy was performed in 38 patients (66.7%).
Morbidity and 90-day mortality rates were 61.4 and 28 per cent, respectively.
Five patients were reoperated (8.8%). Median hospital stay was 23.5 days. The
mortality rate was higher among patients with spontaneous and tumoral perforation
(54.5 and 100%; P = 0.009), delayed diagnosis (>24 hours; P = 0.0001), and
abdominal/thoracic location (37.5%; P = 0.05). No statistical differences were
found between surgical and conservative/endoscopic management (31% vs 20%; P =
0.205) although hospital staying was longer in surgical group (36.30 days vs
15.63 days; P = 0.029). Esophageal perforation was associated with high morbidity
and mortality rates. Global outcomes depend on etiology, site of perforation, and
delay in diagnosis. An individualized approach for each patient should be chosen
to prevent septic complications of this potentially fatal disease.
PMID- 29966570
TI - Reinforcement of the Staple Line during Gastric Sleeve: A Comparison of
Buttressing or Oversewing, versus No Reinforcement- A Single-Institution Study.
AB - Laparoscopic sleeve gastrectomy (LSG) is a well-established treatment for morbid
obesity. Staple line leak (SLL) remains one of the most serious and life
threatening complications after LSG; however, no consensus exists for prevention.
The purpose of this study is to review and compare the different methods of
staple line management used at our institution. Retrospective review of
preoperative, intraoperative, and postoperative factors was performed for all
patients undergoing LSG at a single institution between September 2010 and August
2015. Primary outcome measure was SLL by reinforcement method
(none/Seamguard/Oversewing). A total of 256 patients undergoing LSG were
included, 197 (76.95%) were women and 233 (87.11%) were whites. The patients had
a mean age of 44.64 years and body mass index of 49.24 kg/m-2. Among those
patients, 145 (56.64%) had staple line reinforced with suture (28, 10.94%) or
Gore Seamguard (115, 44.92%) and 111 (43.36%) had no reinforcement, with no
difference in baseline factors between the groups (all P > 0.05). Gastric leaks
were identified in nine patients (3.52%) with no difference between reinforcement
(2.7 vs 2.1%, P = 0.54) or leak test method (air vs methylene blue). However,
oversewing the staple line was associated with higher incidence of stenosis (P <
0.01). SLL after LSG is a serious complication with significant morbidity and
mortality. This study demonstrated that staple line reinforcement does not
provide significant leak reduction but does reduce intraoperative staple line
bleeding. In addition, oversewing the staple line was associated with
postoperative sleeve stenosis without added benefits.
PMID- 29966571
TI - Nationwide Assessment of Factors Associated with Nonoperative Management of
Pediatric Splenic Injury.
AB - To evaluate variation in care nationwide for children with splenic injuries at
pediatric trauma, adult trauma, and nontrauma centers. We used the National
Inpatient Sample from 2001 to 2010 to identify pediatric patients with splenic
injury. We analyzed demographic, clinical, and hospital status characteristics.
The primary objective was comparison of splenectomy rates at pediatric, adult,
and nontrauma centers. We identified 34,599 patients with splenic injury.
Throughout the study, 3,979 (11.5%) patients underwent splenectomy: 8.2 per cent
of patients at pediatric trauma, 17.6 per cent at adult trauma, and 14.5 per cent
at nontrauma centers. Multivariate regression analysis demonstrated patients had
decreased odds of splenectomy at pediatric trauma centers compared with adult and
nontrauma centers (OR = 0.42, P < 0.001). In addition, children aged 14 to 17
years (OR = 2.5) with injury severity score > 14 (OR = 5.8) had increased odds of
undergoing splenectomy. In this nationwide sample, children with splenic injury
treated at adult trauma and nontrauma centers had significantly higher rates of
splenectomy compared with children treated at pediatric trauma centers. We
highlight the need for interventions that ensure all injured children receive
appropriate and high quality trauma care.
PMID- 29966572
TI - Is Hepatopancreatoduodenectomy an Acceptable Operation for Biliary Cancer?
AB - Hepatopancreatoduodenectomy (HPD) is usually indicated for the resection of
locally advanced bile duct (BD) cancer or gallbladder (GB) cancer. Previous
studies have demonstrated a favorable survival rate in BD cancer patients after
HPD if R0 resection is achieved. By contrast, the benefit of HPD for GB cancer
remains controversial. This study aimed to analyze the outcomes of GB and BD
cancer after HPD. Between January 2004 and December 2013, a total of 22 patients
underwent HPD for BD (n = 14) or GB cancer (n = 8). We analyzed the survival,
mortality, morbidity, and prognostic factors. After HPD, the mortality rate was
4.5 per cent and the morbidity rate was 68.2 per cent. Pancreatic fistula
occurred in 50.0 per cent of the patients (grade A, 40.9%; grade B, 9.1%). Liver
failure did not occur. The 1-, 3-, and 5-year survival rates for BD cancer
patients were 57.1, 17.9, and 17.9 per cent and those for GB cancer patients were
62.5, 25.0, and 25.0 per cent, respectively (P = 0.768). In BD cancer,
significant prognostic factors were tumor size, portal vein invasion, multiple
lymph node metastases, and operation time. Furthermore, BD cancer patients with
three or more of risk factors showed poorer survival than those with fewer than
three risk factors. HPD for GB and BD cancer can be performed with acceptable
mortality and morbidity rates. GB cancer patients who underwent HPD showed
comparable survival rates compared with BD cancer patients. Long-term survival
can be achieved in selected patients with BD cancer.
PMID- 29966573
TI - What Is the Relationship between Operative Time and Adverse Events after Colon
and Rectal Surgery?
AB - We propose that prolonged colorectal surgery operative times are associated with
increased 30-day adverse events. We identified a cohort from the American College
of Surgeons National Surgical Quality Improvement Program (NSQIP) from January
2005 through December 2012. Patients who underwent colectomy with primary
anastomosis were selected using CPT codes. Operative time was categorized into
short, average, and long based on mean operative times +/-1 SD. NSQIP-approved
multivariate models were used to identify associations between operative time and
30-day adverse events. A total of 113,615 patients underwent colorectal resection
of which 46 per cent were laparoscopic and 12 per cent were identified as long
operative times. Patients with long operative procedures had 34 per cent more
superficial surgical site infections, 65 per cent more organ space infections, 69
per cent more abdominal dehiscences, 44 per cent more thrombotic complications,
45 per cent more urinary tract infections, 40 per cent more returns to the
operating room, and 36 per cent more prolonged lengths of stay (P < 0.05 for all
analyses). The multivariable analysis revealed an association between long
operative times and increased adverse events despite adjustment for all NSQIP
recommended covariates. Our results reveal increased 30-day adverse events with
increased operative time. We propose that operative time may serve as a proxy for
surgical complexity in colorectal surgery.
PMID- 29966574
TI - Colon and Rectal Neuroendocrine Tumors: Are They Really One Disease? A Single
Institution Experience over 15 Years.
AB - Colon and rectal neuroendocrine tumors (NETs) are often studied as one entity.
Recent evidence suggests that worse outcomes are associated with colon compared
with rectal NETs; direct comparisons are lacking. Our aim was to assess
clinicopathologic, treatment, and survival differences between these diseases.
All patients who underwent resection of colorectal NETs at one institution from
2000 to 2014 were included and analyzed. Of 29 patients, 12(41%) had colon and 17
(59%) had rectal NETs. Baseline demographics were similar between groups,
although colon patients tended to be symptomatic at presentation (67% vs 44%, P =
0.41). Eighty-three per cent of colon patients underwent surgical resection,
whereas 77 per cent of rectal patients underwent endoscopic or transanal
resection (P = 0.003). Colon patients had larger (3.4 cm vs 0.7 cm, P = 0.03),
higher T-stage (T3/T4: 91% vs 14%, P = 0.003), higher grade tumors (42% vs 12%, P
= 0.09) with more lymph nodes (58% vs 24%, P = 0.12) and lymphovascular invasion
positivity (58% vs 24%, P = 0.32). Five-year disease-specific survival was 53%
versus 80 per cent for colon and rectal patients, respectively (P = 0.22). After
excluding high-grade tumors, colon NETs were associated with lymphovascular
invasion positivity (100% vs 17%, P = 0.05) and advanced T-stage (80% vs 8%, P =
0.01). Colon and rectal 5-year disease-specific survival was 67 versus 80 per
cent (P = 0.86). Colon and rectal NETs clinically seem to be distinct entities.
Colon tumors have more aggressive clinicopathologic features, which may translate
to worse outcomes. These differences in tumor biology may demand distinct
management and should be further studied in a multi-institutional setting.
PMID- 29966575
TI - Improved Intraoperative Communication after Utilization of Navigational Grids
during Laparoscopic Cholecystectomies.
AB - Efficient intraoperative communication (IC) between an attending and resident
during surgery is highly valuable. Few tools, however, have been developed to
improve IC. This study evaluates IC between residents and attendings after
utilization of a navigational grid (NG) during laparoscopic cholecystectomies.
Attendings and surgery residents completed a 10-question survey after performing
a laparoscopic cholecystectomy. Surveys were collected for 12 weeks: six weeks
before use of NGs and six weeks with use of NGs. The NGs were constructed to fit
our 26-surgical monitors and allowed the monitors to be divided into a 7 * 4
grid. Hunderd and fifteen surveys were collected: 50 from attendings (pre-NG: 31
vs NG: 19) and 65 from residents (42 vs 23). Before NGs, attendings were less
likely than residents to perceive attending instructions to be clear (64.5 vs
93.0%, P = 0.0001) and less likely to believe IC left little room for confusion
during the procedure (64.5 vs 90.5%, P = 0.007). After NGs, attendings believed
intraoperative directional guidance was more concise and clear (64.5 vs 89.5%, P
= 0.062); they also reported that NGs left little room for IC confusion during
the procedure (64.5 vs 94.7%, P = 0.039). Surveys showed the grid's utility to be
inversely correlated with years of experience. Residents ( 0.05), the average postoperative follow-up duration,
respectively, were 42 months and 22 months, whereas the overall incidence of MCH,
respectively, were 5.2 and 0.5 per cent (P < 0.05). In the first 24 months follow
up time, the overall incidence of MCH, respectively, were 3.6 and 0 per cent.
Laparoscopic evaluation was positive for CPPV in 67 cases. We found the
prevalence of 56.1 per cent of CPPV in LPEC groups aged 0.6 to 2 years old,
finding the incidence gradually decline with the increase of age, until 14.3 per
cent to 10 to 12 years old group. Our study shows LPEC has proven efficacy in
treatment of unilateral inguinal hernia in children, and routine laparoscopic
exploration with this simple maneuver should be actively performed to observe
CPPV in all chidren.
PMID- 29966577
TI - An Age-Based Analysis of Pediatric Melanoma: Staging, Surgery, and Mortality in
the Surveillance, Epidemiology, and End Results Database.
AB - The pediatric melanoma population is not well described, and current guidelines
for their management are not well defined. Our study aims to identify this
population, treatment modalities, and outcomes using a national population-based
database. We reviewed the Surveillance, Epidemiology, and End Results database
(2004-2008). Patients <=21 years old with melanoma were included and grouped into
<=12 years of age, 13 to 18 years, and 19 to 21 years. Clinical characteristics
were analyzed across the groups. A total of 1255 patients were included: 52.7 per
cent were 19 to 21 years of age, 36.3 per cent were 13 to 18 years of age, and
11.0 per cent were <=12 years of age. The 19- to 21-year-olds had the highest
proportion of stage I (50.5%) versus <=12 years of age (31.9%); the <=12-year
olds had the highest proportion of stage IV (3.6%) versus 19 to 21 years of age
(0.9%), P < 0.001. The 19- to 21-year-olds had the highest proportion receiving
wide local excisions only (34.8%) versus <=12 years of age (26.4%); the <=12-year
olds had the highest proportion of patients without any surgeries (16.0%) versus
13 to 18 years of age (9.4%), P = 0.169. On adjusted analysis, the 19- to 21-year
olds had worse survival compared with <=12 years of age (hazard ratio: 5.26, P =
0.017, 95% confidence interval 1.34-20.65). Disparities were found in the <=12
year-old melanoma population, as they had later stage melanomas, less invasive
surgery, and lower survival. Clearer prognostic factors are needed to better
elucidate their management.
PMID- 29966578
TI - Current State of Women in Academic Surgical Subspecialties: How a New Metric in
Measuring Academic Productivity May Change the Equation.
PMID- 29966579
TI - Preoperative Progressive Pneumoperitoneum for Incisional Hernia Repair with Loss
of Domain.
PMID- 29966580
TI - Impact on Survival by Surgical Approach to Simple Cholecystectomy in T1a
Gallbladder Tumors.
PMID- 29966582
TI - 3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates MPP+-induced
cytotoxicity by regulating oxidative stress and mitochondrial dysfunction in SH
SY5Y cells.
AB - Parkinson's disease (PD) is a common chronic neurodegenerative disease mainly
caused by the death of dopaminergic neurons. However, no complete
pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl
4- phenylpyridinium (MPP+)-induced SH-SY5Y neurotoxicity has been broadly
utilized to create cellular models and study the mechanisms and critical aspects
of PD. In the present study, we examined the role of a novel azetidine
derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792),
against MPP+-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792
significantly attenuated MPP+-induced changes in the protein levels of Bcl-2 and
Bax together with efficient suppression of MPP+-induced activation of caspase-3
activity. KHG26792 also attenuated mitochondrial potential and levels of ROS,
Ca2+, and ATP in MPP+-treated SH-SY5Y cells. Additionally, KHG26792 inhibited the
induced production of nitric oxide and malondialdehyde. Moreover, the protective
effect of KHG26792 is mediated through regulation of glutathione peroxidase and
GDNF levels. Our results suggest a possibility that KHG26792 treatment
significantly protects against MPP+-induced neurotoxicity in SH-SY5Y cells and
KHG26792 may be a valuable therapeutic agent for the treatment of PD induced by
an environmental toxin. [BMB Reports 2018; 51(11): 590-595].
PMID- 29966581
TI - Exosomes derived from microRNA-584 transfected mesenchymal stem cells: novel
alternative therapeutic vehicles for cancer therapy.
AB - Exosomes are small membranous vesicles which contain abundant RNA molecules, and
are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one
of the transferred molecules affecting the adopted cells, including glioma cells.
We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading
miRNA and have important effects on the progress of gliomas. To determine these
effects by treating exosomal miRNA in culture media of miRNA mimic transfected
MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and
the expression level of relative proteins associated with cell apoptosis, growth
and migration. For animal studies, the mice injected with U87 cells were exposed
to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence
of exosomal miRNA on the progress of glioma. Based on our results, we propose a
new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs
could be used to modulate tumor progress as the anticancer vehicles. [BMB Reports
2018; 51(8): 406-411].
PMID- 29966583
TI - Cellular coordination controlling organ separation and surface integrity in
plants.
AB - Plants are unable to relocate themselves to a more favorable location and thus
have to deal with developmental programs and environmental cues wherever they
happen to be. It is yet largely unknown how plant cells coordinate cellular
activities and architectures to accomplish developmental processes and respond to
environmental changes. By identifying and establishing a new cellular model
system, we have discovered that two neighboring cell types in the abscission zone
(AZ) of Arabidopsis flowers coordinate their activities to ensure a precise "cut"
through a highly restricted area of plant tissue to bring about organ separation.
From this perspective, we further discuss the essence of cellular coordination in
AZ, the key molecules controlling the organ separation, and relevant
implications. [BMB Reports 2018; 51(7): 317-318].
PMID- 29966584
TI - Factors associated with declining to report the number of sexual partners using
computer-assisted self-interviewing: a cross-sectional study among individuals
attending a sexual health centre in Melbourne, Australia.
AB - Background: The number of sexual partners is one of the most important risk
factors for sexually transmissible infections (STIs), including HIV. The aim of
the present study was to examine the association between declining to report the
number of partners using computer-assisted self-interviewing (CASI) and HIV or
STI positivity at a public sexual health centre in Melbourne, Australia, in 2016.
Methods: Individuals were categorised into three risk populations: women, men who
have sex with women only (MSW) and men who have sex with men (MSM). Logistic
regression analysis was used to examine the association between declining to
report the number of sexual partners in the past 12 months and HIV or STI
positivity for women and MSW, with generalised estimating equations (GEE) used
for estimation in MSM to address repeated-measures within individuals. Results:
In all, 18085 individuals (5579 women, 6013 MSW, 6493 MSM) were included in the
final analysis. There was no association between chlamydia positivity and
declining to respond among women and MSW. MSM who declined to respond were more
likely to be chlamydia positive (adjusted odds ratio1.21; 95% confidence interval
(CI) 1.01-1.43). Known HIV-positive MSM and MSM newly diagnosed with HIV had 3.31
fold (95% CI 2.48-4.42) and 2.82-fold (95% CI 1.84-4.32) greater odds
respectively of declining to respond compared with HIV-negative MSM. Gonorrhoea
and syphilis positivity in MSM were not associated with declining to respond.
Conclusions: There was no association between declining to report the number of
partners and chlamydia positivity among women and MSW. However, MSM who declined
to report the number of partners were slightly more likely to have chlamydia and
substantially more likely to be HIV positive.
PMID- 29966585
TI - a-Tocopherol modifies the expression of genes related to oxidative stress and
apoptosis during invitro maturation and enhances the developmental competence of
rabbit oocytes.
AB - The developmental competence of invitro maturation (IVM) oocytes can be enhanced
by antioxidant agents. The present study investigated, for the first time in the
rabbit model, the effect of adding alpha-tocopherol (0, 100, 200 and 400uM)
during IVM on putative transcripts involved in antioxidant defence (superoxide
dismutase 2, mitochondrial (SOD2), glutathione peroxidase 1 (GPX1), catalase
(CAT)), cell cycle regulation and apoptosis cascade (apoptosis tumour protein 53
(TP53), caspase 3, apoptosis-related cysteine protease (CASP3)), cell cycle
progression (cellular cycle V-Akt murine thymoma viral oncogene homologue 1
(AKT1)), cumulus expansion (gap junction protein, alpha 1, 43 kDa (GJA1) and
prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclo
oxygenase) (PTGS2)) and metabolism (glucose-6-phosphate dehydrogenase (G6PD)).
Meiotic progression, mitochondrial reallocation, cumulus cell apoptosis and the
developmental competence of oocytes after IVF were also assessed. Expression of
SOD2, CAT, TP53, CASP3 and GJA1 was downregulated in cumulus-oocyte complexes
(COCs) after IVM with 100MUM alpha-tocopherol compared with the group without the
antioxidant. The apoptotic rate and the percentage of a non-migrated
mitochondrial pattern were lower in COCs cultured with 100MUM alpha-tocopherol,
consistent with better-quality oocytes. In fact, early embryo development was
improved when 100MUM alpha-tocopherol was included in the IVM medium, but
remained low compared with invivo-matured oocytes. In conclusion, the addition of
100MUM alpha-tocopherol to the maturation medium is a suitable approach to manage
oxidative stress and apoptosis, as well as for increasing the in vitro
developmental competence of rabbit oocytes.
PMID- 29966586
TI - Structural basis of malodour precursor transport in the human axilla.
AB - Mammals produce volatile odours that convey different types of societal
information. In Homo sapiens, this is now recognised as body odour, a key
chemical component of which is the sulphurous thioalcohol, 3-methyl-3
sulfanylhexan-1-ol (3M3SH). Volatile 3M3SH is produced in the underarm as a
result of specific microbial activity, which act on the odourless dipeptide
containing malodour precursor molecule, S-Cys-Gly-3M3SH, secreted in the axilla
(underarm) during colonisation. The mechanism by which these bacteria recognise S
Cys-Gly-3M3SH and produce body odour is still poorly understood. Here we report
the structural and biochemical basis of bacterial transport of S-Cys-Gly-3M3SH by
Staphylococcus hominis, which is converted to the sulphurous thioalcohol
component 3M3SH in the bacterial cytoplasm, before being released into the
environment. Knowledge of the molecular basis of precursor transport, essential
for body odour formation, provides a novel opportunity to design specific
inhibitors of malodour production in humans.
PMID- 29966588
TI - Variation in mitochondrial respiratory capacity and myosin heavy chain
composition in repeated muscle biopsies.
AB - Skeletal muscle is a heterogeneous tissue and it is essential to know the
methodological variation and reliability when measuring aspects of muscle
function. We assessed the methodological and biological variation when measuring
mitochondrial respiratory capacity (MRC), citrate synthase (CS) activity and
myosin heavy chain (MHC) composition in muscle biopsies from nine healthy male
participants, and in addition we assessed variation in MRC in isolated
mitochondria and yeast suspension. We analysed MRC, CS activity and MHC
composition in duplicates (intra-biopsy variation) to quantify the methodological
variation, as well as the biological variation from multiple muscle biopsies
(inter-biopsy variation) obtained at different sites of the same muscle. Three
muscle biopsies (B1, B2 and B3) were obtained from each subject in m. vastus
lateralis. Two of the biopsies were from the same leg and one from the other leg.
For MRC, intra-biopsy coefficient of variation (CV) was 8.4% and inter-biopsy CV
was 13.3%. For MHC type I, IIa and IIx intra-biopsy CV was 8.3, 6.0 and 22.3%,
respectively. Inter-biopsy CV for these MHC types were 21.5, 15.4 and 42.0%,
respectively. For CS activity intra-biopsy CV was 0.6% and inter-biopsy CV was
15.3%. No differences between B1, B2 and B3 were detected for MRC, CS activity or
MHC composition.
PMID- 29966589
TI - Development of peptide-based chemiluminescence enzyme immunoassay (CLEIA) for
diagnosis of dengue virus infection in human.
AB - Dengue is the most prevalent mosquito-borne viral disease in tropical and
subtropical regions worldwide. Since its clinical symptoms are non-specific and
easily mistaken as other kinds of infection, laboratory diagnosis is required to
confirm dengue infections. In this study, ten peptides (E1-E10) from the envelope
protein of dengue virus (DENV) were first identified using bioinformatic tool.
The screened peptides were then synthesized for the peptide-based
chemiluminescence enzyme immunoassay (CLEIA). Two peptides, E1 and E7, were found
as the best candidate antigen and therefore used as downstream application in the
development of low-cost peptide-based anti-DENV immunoglobulin M antibodies (IgM)
indirect CLEIA. 176 serum samples were used to study the presence of anti-DENV
IgM antibodies to evaluate the diagnostic ability of IgM-CLEIA. Receiver
operating characteristic curve (ROC) was used to estimate the diagnostic cut-off
value. The sensitivity and the specificity reached 82.5% and 94.6% respectively
when peptide E1 was used, but declined to 79.2% and 92.9% respectively when
peptide E7 was used. Therefore, the combination of E1 and E7 was used to improve
the sensitivity and the specificity to 85.0% and 96.4% respectively in 1.5 h
assay time, providing a potentially practical use for the diagnosis of DENV
infections in patients' serum.
PMID- 29966587
TI - Nanoscale dysregulation of collagen structure-function disrupts mechano
homeostasis and mediates pulmonary fibrosis.
AB - Matrix stiffening with downstream activation of mechanosensitive pathways is
strongly implicated in progressive fibrosis; however, pathologic changes in
extracellular matrix (ECM) that initiate mechano-homeostasis dysregulation are
not defined in human disease. By integrated multiscale biomechanical and
biological analyses of idiopathic pulmonary fibrosis lung tissue, we identify
that increased tissue stiffness is a function of dysregulated post-translational
collagen cross-linking rather than any collagen concentration increase whilst at
the nanometre-scale collagen fibrils are structurally and functionally abnormal
with increased stiffness, reduced swelling ratio, and reduced diameter. In ex
vivo and animal models of lung fibrosis, dual inhibition of lysyl oxidase-like
(LOXL) 2 and LOXL3 was sufficient to normalise collagen fibrillogenesis, reduce
tissue stiffness, and improve lung function in vivo. Thus, in human fibrosis,
altered collagen architecture is a key determinant of abnormal ECM structure
function, and inhibition of pyridinoline cross-linking can maintain mechano
homeostasis to limit the self-sustaining effects of ECM on progressive fibrosis.
PMID- 29966590
TI - A Novel Risk Score Predicts Operative Mortality After Acute Type A Aortic
Dissection Repair.
AB - BACKGROUND: Current stratification systems for patients presenting with acute
type A aortic dissection rely on signs of malperfusion to predict mortality. The
authors sought to develop an algorithm to readily risk stratify these patients
using admission characteristics. METHODS: Two hundred sixty-nine consecutive
patients who underwent type A repair between 2002 and 2015 were reviewed for
easily obtainable preoperative demographics and laboratory values deemed a priori
as potential predictors of operative mortality. Multiple logistic regression
analysis was performed to determine independent significance, and linear
regression was performed to generate the concomitant regression expression of the
variables significant on bivariate analysis. RESULTS: Operative mortality was 16%
(43/269) and was 29% (34/119) among patients who presented with malperfusion.
Upon multivariate analysis, creatinine (p = 0.008), liver malperfusion (p =
0.006), and lactic acid level (p = 0.0007) remained independent significant
predictors. Regression coefficients allowed the generation of a risk score as 5.5
* (lactic acid [mmol/L]) + 8 * (creatinine [mg/dL]) +/- 8 (+ if liver
malperfusion presents, - if no liver malperfusion). Upon receiver-operating
characteristic curve analysis this model generated a c-statistic of 0.75.
Operative mortality among patients within the lowest tertile (risk score < 7) was
4%, whereas patients in the middle (7 to 20) and highest (>=20) tertiles had
mortality rates of 14% 37%, respectively. CONCLUSIONS: Although still requiring
external validation, the innovative risk score presented necessitates knowledge
of lactic acid, serum creatinine, and liver function tests. The algorithm
predicts operative mortality with high accuracy and offers clinicians a novel
tool to improve preoperative guidance and prognosis.
PMID- 29966591
TI - Early Diagnostic Features of Left-to-Right Shunt-Induced Pulmonary Arterial
Hypertension in Piglets.
AB - BACKGROUND: We aimed to establish early diagnostic characteristics of left-to
right shunt-induced pulmonary arterial hypertension (PAH) in a piglet model.
METHODS: A shunt-induced PAH in piglets (n = 9) was successfully established by
anastomosis of vascular prosthesis from aorta to pulmonary artery with follow-up
for 6 months by a number of diagnostic procedures. RESULTS: PAH developed with
mean pulmonary arterial pressure [PAP] of 30.2 +/- 6.0 mm Hg immediately after
operation and 33.5 +/- 8.7 mm Hg at 3 months after operation with pulmonary
vascular resistance increased to 4.0 +/- 0.9 Wood units. There was a weak
correlation on systolic PAP between catheterization and echocardiography but the
Tei index was significantly correlated to systolic PAP. Magnetic resonance
imaging demonstrated that the end-diastolic volume index, systolic volume index,
ejection fraction of the ventricle, and ventricular mass index were sensitive
indices. Technetium-99m single-photon emission computed tomography indicated
increased blood flow in the upper and middle zones of both lungs. Positron
emission tomography-computed tomography (PET-CT) demonstrated a higher kilo count
(kct) of 18F-fluorodeoxyglucose in the right ventricular wall and both chambers
at 3 months postoperatively (right ventricular wall: 5,708.3 +/- 428.4 versus
3,965.5 +/- 138.6 preoperatively, p = 0.003; both chambers: 2,963.6 +/- 219.4
versus 1,710.1 +/- 35.4 preoperatively, p < 0.05) as well as at 6 months for both
chambers (p < 0.05). CONCLUSIONS: In this successful left-to-right shunt-induced
PAH model in piglets, sensitive indices including the Tei index, systolic volume
index, ejection fraction, ventricular mass index, lung perfusion, and
glycometabolism by PET-CT in early PAH are determined. For the first time, we
report that glycometabolism by PET-CT is useful in early diagnosis. These indices
may be used for the early diagnosis in the left-to-right shunt-induced PAH.
PMID- 29966593
TI - Adventitial Wrap Technique for Acute Type A Aortic Dissection.
AB - We describe a simple and reproducible technique to achieve complete and immediate
hemostasis of the distal anastomosis in total arch replacement with the frozen
elephant trunk technique. The adventitia was left seamlessly 1.0 cm longer than
the level of the suture line. The adventitial remnant covered most of the distal
anastomosis line tightly while the distal anastomosis was completed with
continuous sutures. The adventitia was thin and tough, making it suitable to
cover the suture line. This technique can contribute to eliminating bleeding from
the distal anastomosis independent of unreliable blood coagulability during
aortic surgery for acute aortic dissection.
PMID- 29966592
TI - Robotic Mitral Valve Repair in Older Individuals: An Analysis of The Society of
Thoracic Surgeons Database.
AB - BACKGROUND: National outcomes of robotic mitral valve repair (rMVr) compared with
sternotomy (sMVr) in older patients are currently unknown. METHODS: From 2011 to
2014, all patients aged 65 years and older undergoing MVr in The Society of
Thoracic Surgeons Adult Cardiac Surgery Database linked to Medicare claims data
were identified. Patients who underwent rMVr were propensity matched to patients
who underwent sMVr. Standard differences and falsification outcome of baseline
characteristics were tested to ensure a balanced match. Cox models were used to
calculate 3-year mortality, heart failure readmission, and mitral valve
reintervention, adjusting for competing risks where appropriate. RESULTS: After
matching, 503 rMVr patients from 65 centers and 503 sMVr from 251 centers were
included. There were no significant differences in comorbidities or falsification
outcome. Cardiopulmonary bypass and cross-clamp times were longer with rMVr
versus sMVr at 125 versus 102 minutes (p < 0.0001) and 85 versus 75 minutes (p <
0.0001), respectively. The rMVr patients had shorter intensive care unit (27 vs
47 hours, p < 0.0001) and hospital stay (5 vs 6 days, p < 0.0001), less frequent
transfusion (21% vs 35%, p < 0.0001), and less atrial fibrillation (28% vs 40%, p
< 0.0001). Three-year mortality (hazard ratio, 1.21; 95% confidence interval,
0.68 to 2.16; p = 0.52), heart failure readmission (hazard ratio, 1.42; 95%
confidence interval, 0.80 to 2.52, p = 0.10), and mitral valve reintervention
(hazard ratio, 0.42; 95% confidence interval, 0.15 to 1.18; p = 0.22) did not
differ between the groups. CONCLUSIONS: The rMVr procedure was associated with
less atrial fibrillation, less frequent transfusion requirement, and shorter
intensive care unit and hospital stay, without a significant difference in 3-year
mortality, heart failure readmission, or mitral valve reintervention. In older
patients, rMVr confers short-term advantages without a detriment to midterm
outcomes.
PMID- 29966594
TI - Pericardial Pleomorphic Mesothelioma and Heart Failure: A Unique Case.
PMID- 29966595
TI - Use of Bilateral Mammary Artery: Redefining Indications After a Quick Glance at
the Coronary Status?
PMID- 29966596
TI - Mechanical Versus Bioprosthetic Aortic Valve Replacement in Patients Aged 50
Years and Younger.
AB - BACKGROUND: This study evaluated outcomes in younger patients, specifically aged
50 years and younger, after mechanical aortic valve replacement (mAVR) and
bioprosthetic AVR (bAVR). METHODS: From 1994 to 2016, 643 patients underwent AVR
(411 mAVR and 232 bAVR) at age 50 or younger. Concomitant coronary artery bypass
grafting and mitral valve procedures were also included. Propensity score
matching methods resulted in 170 evenly matched patient pairs. Primary end points
were operative mortality and long-term survival. Secondary end points were
stroke, major bleeding, and redo AVR. Median observation time was 8.1 years
(range, 0 to 23.6 years). RESULTS: Overall, mean age was 41.9 years, and 29.3%
were women, with an increasing trend toward use of bAVR. Mean age in the matched
patients was 43.3 years for both cohorts (p = 0.68). Operative mortality, stroke,
atrial fibrillation, reoperation for bleeding, and readmission rates within 30
days were all similar between the two groups. bAVR patients were at higher risk
for redo AVR (13% vs 1.6%, p < 0.001), and mAVR patients were at higher risk for
major bleeding events (8.5% vs 2.2%, p = 0.006). However, when adjusted, there
were no differences in midterm and long-term survival between unmatched and
matched cohorts. CONCLUSIONS: The increased risk of reoperation for bAVR and
major bleeding incidents for mAVR was not reflected in midterm and long-term
survival differences between the two groups. Our results suggest that bAVR may be
an acceptable prosthesis choice for some patients aged 50 years and younger,
although the results should be taken with caution.
PMID- 29966597
TI - Titration of cell-associated varicella-zoster virus with the MV9G reporter cell
line for antiviral studies.
AB - Titration of the cell-associated virus (CAV) of varicella-zoster virus (VZV) is
essential for antiviral studies. A VZV reporter cell line, MV9G, generated in our
previous study expresses firefly luciferase upon CAV infection in a dose
dependent manner, suggesting that use of the cell line for titration is feasible.
In this study, MeWo cells infected with VZV vaccine Oka (vOka) strain or with
clinical isolates obtained from patients with varicella or zoster were used as
CAV. A co-culture of MV9G cells with the virus-infected MeWo cells were set up
and optimized for titration of CAV. Luciferase activities of MV9G cells measured
as relative light units (RLUs) of chemiluminescence correlated well (r > 0.9, p <
0.05) both with quantities of viral DNAs measured by TaqMan PCR and with numbers
of viral foci detected by immunostaining with a monoclonal antibody against VZV
IE62. In addition, the usefulness of MV9G for antiviral studies was exemplified
by treatment of the VZV-infected cells with various concentrations of acyclovir.
Thus, the reporter cell-based titration of CAV by measuring the induced RLUs may
be a reliable way to estimate viral foci and viral DNAs.
PMID- 29966599
TI - Of mice and motion: Behavioural-EEG phenotyping of Alzheimer's disease mouse
models.
AB - BACKGROUND: Rodent electroencephalography (EEG) in preclinical research is
frequently conducted in behaving animals. EEG analysis is complicated by a number
of confounds, particularly 1. The close relationship between EEG power and
movement speed must be controlled for prior to further analysis. 2. The
difficulty inherent in identifying EEG epochs associated with a particular
behaviour. NEW METHOD: We utilized infra-red event stamping to accurately
synchronize EEG recorded from superficial sites above the hippocampus and
prefrontal cortex with motion tracking data in a transgenic Alzheimer's disease
(AD) mouse model (PLB1APP) and wild-type controls (PLBWT) performing a Y-maze
spontaneous alternation task. Video tracking synchronized epochs capturing
specific behaviours were automatically identified and extracted prior to auto
regressive spectral analysis. RESULTS: Despite comparable behavioural
performance, PLB1APP mice demonstrated region and behavioural context specific
deficits in regulation of Gamma power: In contrast to controls, hippocampal gamma
response to speed as well as prefrontal activity associated with correct vs.
incorrect alternations was absent in PLB1APP mice. Regulation of hippocampal
Gamma power in response to direction of movement did not differ. COMPARISON WITH
EXISTING METHODS: This method allows for the first time to detect behaviour
specific differences in EEG response to speed that can be quantified and actively
controlled for. Analysis across multiple parameters engaging different brain
regions can now be used for detailed EEG profiling of brain-region specific
functions. CONCLUSION: Combining infrared event-stamping and auto-regressive
modelling enables rapid, automated and sensitive phenotyping of AD mouse models.
Subtle alterations in brain signalling can be detected prior to overt behavioural
impairments.
PMID- 29966600
TI - Geometric classification of brain network dynamics via conic derivative
discriminants.
AB - BACKGROUND: Over the past decade, pattern decoding techniques have granted
neuroscientists improved anatomical specificity in mapping neural representations
associated with function and cognition. Dynamical patterns are of particular
interest, as evidenced by the proliferation and success of frequency domain
methods that reveal structured spatiotemporal rhythmic brain activity. One
drawback of such approaches, however, is the need to estimate spectral power,
which limits the temporal resolution of classification. NEW METHOD: We propose an
alternative method that enables classification of dynamical patterns with high
temporal fidelity. The key feature of the method is a conversion of time-series
data into temporal derivatives. By doing so, dynamically-coded information may be
revealed in terms of geometric patterns in the phase space of the derivative
signal. RESULTS: We derive a geometric classifier for this problem which
simplifies into a straightforward calculation in terms of covariances. We
demonstrate the relative advantages and disadvantages of the technique with
simulated data and benchmark its performance with an EEG dataset of covert
spatial attention. We reveal the timecourse of covert spatial attention and, by
mapping the classifier weights anatomically, its retinotopic organization.
COMPARISON WITH EXISTING METHOD: We especially highlight the ability of the
method to provide strong group-level classification performance compared to
existing benchmarks, while providing information that is complementary with
classical spectral-based techniques. The robustness and sensitivity of the method
to noise is also examined relative to spectral-based techniques. CONCLUSION: The
proposed classification technique enables decoding of dynamic patterns with high
temporal resolution, performs favorably to benchmark methods, and facilitates
anatomical inference.
PMID- 29966598
TI - Post-translational modifications of transporters.
AB - Drug transporter proteins are critical to the distribution of a wide range of
endogenous compounds and xenobiotics such as hormones, bile acids, peptides,
lipids, sugars, and drugs. There are two classes of drug transporters- the solute
carrier (SLC) transporters and ATP-binding cassette (ABC) transporters -which
predominantly differ in the energy source utilized to transport substrates across
a membrane barrier. Despite their hydrophobic nature and residence in the
membrane bilayer, drug transporters have dynamic structures and adopt many
conformations during the translocation process. Whereas there is significant
literature evidence for the substrate specificity and structure-function
relationship for clinically relevant drug transporters proteins, there is less of
an understanding in the regulatory mechanisms that contribute to the functional
expression of these proteins. Post-translational modifications have been shown to
modulate drug transporter functional expression via a wide range of molecular
mechanisms. These modifications commonly occur through the addition of a
functional group (e.g. phosphorylation), a small protein (e.g. ubiquitination),
sugar chains (e.g. glycosylation), or lipids (e.g. palmitoylation) on solvent
accessible amino acid residues. These covalent additions often occur as a result
of a signaling cascade and may be reversible depending on the type of
modification and the intended fate of the signaling event. Here, we review the
significant role in which post-translational modifications contribute to the
dynamic regulation and functional consequences of SLC and ABC drug transporters
and highlight recent progress in understanding their roles in transporter
structure, function, and regulation.
PMID- 29966601
TI - Effects of combined pre- and post-natal enrichment on anxiety-like, social, and
cognitive behaviours in juvenile and adult rat offspring.
AB - The pre- and post-natal periods are characterized by unrivalled growth and are
sensitive to environmental changes. A correctly stimulating early environment is
essential for developing natural behaviors and maintaining affective wellness.
Five litters of rat progeny were co-housed through gestation until juvenile age
in housing providing physical and social enrichment. Five control litters were
housed separately in standard conditions. Half of the offspring were tested in
the elevated plus-maze and the social interaction test as juveniles (five weeks
old) with the other half tested in the Morris water maze. As adults (11 weeks
old), the testing groups were reversed. Weight was monitored weekly. Enriched
offspring had leaner body weights. In the elevated plus-maze, control juvenile
progeny spent a higher percentage of time in the open arms, showed greater
locomotor activity, less grooming, and more rearing (males only). In the social
interaction test, enriched juvenile offspring were found to sniff their
conspecific more, display more self-grooming behaviour as well as show less
locomotor activity and body contact. In the Morris water maze probe test,
enriched rats demonstrated improved memory for the platform position and more
effective search strategies with increased platform crossings, middle crossing as
well as more time spent in the platform quadrant and less thigmotaxis behaviour.
Adult female rat offspring also demonstrated superior memory for the platform
position and crossed the maze middle more often. These results suggest that
combined pre- and post-natal environmental enrichment influences physiology and
behaviour in offspring rats with some of those influences being long-lasting.
PMID- 29966602
TI - Functional and Objective Results of Urinary Undiversions in Oncologic Patients.
AB - OBJECTIVE: To review surgical outcomes in urinary undiversions and describe short
and long-term complications. METHODS: Retrospective review of patients who
underwent urinary undiversion in our institution between May 2010 and May 2016.
Complications were graded according to the Clavien classification. All patients
completed the Patient Global Impression of Improvement questionnaire to indicate
overall satisfaction with urinary undiversion. RESULTS: Median time from the
cystectomy to undiversion was 29 months (range 11-53 months). Five patients (55%)
reported significant distress related to the ileal conduit and were undiverted
into an orthotopic neobladder. A female patient with an orthotopic neobladder and
severe urinary incontinence received neobladder neck closure and catheterizable
channel. Another female patient with an orthotopic neobladder was undiverted into
an Indiana Pouch. Complications during the first 60 days were mostly minor,
Clavien I (1 patient), 5 patients Clavien II, and a patient with Clavien IIIb.
Patient Global Impression of Improvement questionnaire scores showed that 6
patients (67%) felt "Very much better" and 3 patients (33%) felt "Much better"
after urinary undiversion 60%. CONCLUSION: After urinary undiversions, minor
complication rate is high, and major complication rate is considerable. Urinary
undiversions are a highly complex, yet feasible procedure, which requires
experienced multidisciplinary teams and demands appropriate patient selection.
Patients, after undiversions show a high degree of satisfaction with long-term
satisfactory outcomes, which points out the need for consideration for these
procedures once the oncologic disease is controlled.
PMID- 29966603
TI - Whole Exome Sequencing of a Consanguineous Turkish Family Identifies a Mutation
in GTF2H3 in Brothers With Spermatogenic Failure.
AB - In this case report we describe our investigation into the genetic cause of
infertility due to idiopathic nonobstructive azoospermia in a consanguineous
Turkish family. We extracted DNA from blood and applied whole exome sequencing on
4 infertile brothers in this family diagnosed with oligo- and azoospermia.
Standard bioinformatics analysis pipelines were run including alignment to the
reference genome, variant calling, and quality control filtering. Potentially
pathogenic variants were identified and prioritized using genetic variant
annotation software and public variant frequency databases, followed by
validation with Sanger sequencing. A nonsynonymous variant in "general
transcription factor TFIIH subunit 3" (GTF2H3) was identified in this
consanguineous family. This variant in chromosome 12 (12chr: 124144111 T>C,
p.Ser222Pro) of GTF2H3 represents a likely a disease-causing mutation as it is
predicted to be damaging, rare, segregates with the disease, and is highly
evolutionarily conserved. Familial segregation analysis of the variant showed
that it was present as a homozygous mutation in the brothers with nonobstructive
azoospermia, and heterozygous mutation in the oligospermic brothers. We propose a
mechanism by which this variant leads to deficits in Vitamin A signaling, which
is essential for spermatogenesis.
PMID- 29966605
TI - Clioquinol increases the expression of interleukin-8 by down-regulating GATA-2
and GATA-3.
AB - Clioquinol was used in the mid-1900s as an amebicide to treat indigestion and
diarrhea. However, it was withdrawn from the market in Japan because it was
linked to subacute myelo-optic neuropathy (SMON). The pathogenesis of SMON has
not yet been elucidated in detail. As reported previously, we performed a global
analysis on human neuroblastoma cells using DNA chips. The global analysis and
quantitative PCR demonstrated that the mRNA level of interleukin-8 (IL-8) was
significantly increased when SH-SY5Y neuroblastoma cells were treated with
clioquinol. An enzyme-linked immunosorbent assay also demonstrated that
clioquinol induced the secretion of IL-8 into culture media. Promoter analyses on
SH-SY5Y cells revealed that a region responsive to clioquinol exists between -152
and -144 of the human IL-8 gene, which contains a consensus GATA-binding site
sequence. The introduction of mutations at this site or the activator protein
(AP)-1 site sequence at -126/-120 significantly reduced clioquinol-induced
transcriptional activation. Among the GATA transcription factors expressed in SH
SY5Y cells, GATA-2 and GATA-3 protein levels were significantly decreased by the
addition of clioquinol. Electrophoresis mobility shift assays using a probe
corresponding to -159/-113 of the human IL-8 gene revealed two major shifted
bands, one of which was increased and the other was decreased by clioquinol. The
introduction of mutations showed that the former corresponded to binding to the
AP-1 site, and the latter to binding to the GATA site. Supershift analyses
revealed that the binding of c-Jun and c-Fos was increased, whereas that of GATA
3 was decreased by clioquinol. Genome editing against GATA-2 or GATA-3, not GATA
4 significantly enhanced clioquinol-induced IL-8 mRNA expression. On the other
hand, the stable expression of GATA-2 or GATA-3 attenuated clioquinol-induced IL
8 mRNA expression and IL-8 secretion. These results suggest that the clioquinol
induced suppression of GATA-2 and GATA-3 expression mediates the up-regulation of
IL-8.
PMID- 29966606
TI - Intranasal delivery of a novel acetylcholinesterase inhibitor HLS-3 for treatment
of Alzheimer's disease.
AB - AIM: The present study aims to investigate the pharmacokinetics and
pharmacodynamics of HLS-3, a tacrine dimer with high anti-acetylcholinesterase
activity for the treatment of Alzheimer's disease. MAIN METHODS: In vitro Calu-3
and Caco-2 cell monolayer transport and liver microsomal incubation studies of
HLS-3 were carried out to evaluate its nasal epithelium and intestinal membrane
permeability, transporters involved in absorption and hepatic metabolism. In vivo
pharmacokinetics of HLS-3 followed by central and peripheral cholinergic mediated
responses and ex vivo AChE activities in rats via oral and intranasal
administrations were further investigated and compared. KEY FINDINGS: Our in
vitro studies suggested that HLS-3 is the substrate of both P-gp and MRPs with no
significant hepatic oxidation and glucuronidation metabolism. Oral administration
only delivered trace amount of HLS-3 in systemic circulation with a high faecal
recovery of 70.7%, whereas intranasal administration demonstrated an absolute
bioavailability of 28.9% with urinary and faecal recoveries of 1.5% and 34.0%,
respectively. In comparison to oral administration of HLS-3, intranasally
delivered HLS-3 exhibited significant higher central cholinergic mediated
responses without obvious peripheral side effect. SIGNIFICANCE: Intranasal
delivery of HLS-3 with better pharmacokinetics and pharmacodynamics performances
provides a promising approach for treatment of Alzheimer's disease.
PMID- 29966604
TI - Hedgehog signaling from the Posterior Signaling Center maintains U-shaped
expression and a prohemocyte population in Drosophila.
AB - Hematopoietic progenitor choice between multipotency and differentiation is
tightly regulated by intrinsic factors and extrinsic signals from the surrounding
microenvironment. The Drosophila melanogaster hematopoietic lymph gland has
emerged as a powerful tool to investigate mechanisms that regulate hematopoietic
progenitor choice in vivo. The lymph gland contains progenitor cells, which share
key characteristics with mammalian hematopoietic progenitors such as quiescence,
multipotency and niche-dependence. The lymph gland is zonally arranged, with
progenitors located in medullary zone, differentiating cells in the cortical
zone, and the stem cell niche or Posterior Signaling Center (PSC) residing at the
base of the medullary zone (MZ). This arrangement facilitates investigations into
how signaling from the microenvironment controls progenitor choice. The
Drosophila Friend of GATA transcriptional regulator, U-shaped, is a conserved
hematopoietic regulator. To identify additional novel intrinsic and extrinsic
regulators that interface with U-shaped to control hematopoiesis, we conducted an
in vivo screen for factors that genetically interact with u-shaped. Smoothened, a
downstream effector of Hedgehog signaling, was one of the factors identified in
the screen. Here we report our studies that characterized the relationship
between Smoothened and U-shaped. We showed that the PSC and Hedgehog signaling
are required for U-shaped expression and that U-shaped is an important intrinsic
progenitor regulator. These observations identify a potential link between the
progenitor regulatory machinery and extrinsic signals from the PSC. Furthermore,
we showed that both Hedgehog signaling and the PSC are required to maintain a
subpopulation of progenitors. This led to a delineation of PSC-dependent versus
PSC-independent progenitors and provided further evidence that the MZ progenitor
population is heterogeneous. Overall, we have identified a connection between a
conserved hematopoietic master regulator and a putative stem cell niche, which
adds to our understanding of how signals from the microenvironment regulate
progenitor multipotency.
PMID- 29966607
TI - Salinomycin-induced autophagy blocks apoptosis via the ATG3/AKT/mTOR signaling
axis in PC-3 cells.
AB - AIMS: This study evaluated the mechanism by which salinomycin-induced autophagy
blocks apoptosis in PC-3 prostate cancer cells. MAIN METHODS: The anti-cancer
effects of salinomycin in PC-3 cells were confirmed by flow cytometry, JC-1
staining and western blotting. Then, the autophagic effects were measured by
western blotting, GFP-LC3 puncta formation assay, immunofluorescence staining and
electron microscopy. Furthermore, we used lentivirus-mediated shRNA to silence
ATG3, ATG5 and ATG7 expression in PC-3 cells to investigate the regulatory
mechanisms of salinomycin-induced autophagy. KEY FINDINGS: Salinomycin could
induce apoptosis and autophagy in PC-3 cells. Interestingly, autophagy inhibition
could enhance salinomycin-induced apoptosis. We further showed that ATG3, a known
critical regulator of autophagy, was downregulated and involved in the inhibition
of apoptosis by salinomycin-induced autophagy via the AKT/mTOR signaling axis.
SIGNIFICANCE: Our data indicated that salinomycin-induced autophagy blocks
apoptosis via the ATG3/AKT/mTOR signaling axis in PC-3 cells, which provides new
clues for the mechanisms of underlying the anti-cancer effects of salinomycin.
PMID- 29966608
TI - Drug Response Prediction by Globally Capturing Drug and Cell Line Information in
a Heterogeneous Network.
AB - One of the most important problem in personalized medicine research is to
precisely predict the drug response for each patient. Due to relationships
between drugs, recent machine learning-based methods have solved this problem
using multi-task learning models. However, chemical relationships between drugs
have not been considered. In addition, using very high dimensions of -omics data
(e.g., genetic variant and gene expression) also limits the prediction power. A
recent dual-layer network-based method was proposed to overcome these limitations
by embedding gene expression features into a cell line similarity network and
drug relationships in a chemical structure-based drug similarity network.
However, this method only considered neighbors of a query drug and a cell line.
Previous studies also reported that genetic variants are less informative to
predict an outcome than gene expression. Here, we develop a novel network-based
method, named GloNetDRP, to overcome these limitations. Besides gene expression,
we used the genetic variant to build another cell line similarity network. First,
we constructed a heterogeneous network of drugs and cell lines by connecting a
drug similarity network and a cell line similarity network by known drug-cell
line responses. Then, we proposed a method to predict the responses by exploiting
not only the neighbors but also other drugs and cell lines in the heterogeneous
network. Experimental results on two large-scale cell line data sets show that
prediction performance of GloNetDRP on gene expression and genetic variant data
is comparable. In addition, GloNetDRP outperformed dual-layer network- and
typical multi-task learning-based methods.
PMID- 29966609
TI - The Arabidopsis Histone Chaperone FACT: Role of the HMG-Box Domain of SSRP1.
AB - Histone chaperones play critical roles in regulated structural transitions of
chromatin in eukaryotic cells that involve nucleosome disassembly and reassembly.
The histone chaperone FACT is a heterodimeric complex consisting in plants and
metazoa of SSRP1/SPT16 and is involved in dynamic nucleosome reorganization
during various DNA-dependent processes including transcription, replication and
repair. The C-terminal HMG-box domain of the SSRP1 subunit mediates interactions
with DNA and nucleosomes in vitro, but its relevance in vivo is unclear. Here, we
demonstrate that Arabidopsis ssrp1-2 mutant plants express a C-terminally
truncated SSRP1 protein. Although the structure of the truncated HMG-box domain
is distinctly disturbed, it still exhibits residual DNA-binding activity, but has
lost DNA-bending activity. Since ssrp1-2 plants are phenotypically affected but
viable, the HMG-box domain may be functionally non-essential. To examine this
possibility, SSRP1?HMG completely lacking the HMG-box domain was studied.
SSRP1?HMG in vitro did not bind to DNA and its interactions with nucleosomes were
severely reduced. Nevertheless, the protein showed a nuclear mobility and protein
interactions similar to SSRP1. Interestingly, expression of SSRP1?HMG is almost
as efficient as that of full-length SSRP1 in supporting normal growth and
development of the otherwise non-viable Arabidopsis ssrp1-1 mutant. SSRP1?HMG is
structurally similar to the fungal ortholog termed Pob3 that shares clear
similarity with SSRP1, but it lacks the C-terminal HMG-box. Therefore, our
findings indicate that the HMG-box domain conserved among SSRP1 proteins is not
critical in Arabidopsis, and thus, the functionality of SSRP1/SPT16 in
plants/metazoa and Pob3/Spt16 in fungi is perhaps more similar than anticipated.
PMID- 29966610
TI - Oral corticosteroids in preschool children with severe episodes of virus
associated wheeze: To treat or not to treat?
PMID- 29966611
TI - Sweet Predictions Speak Volumes for Early Detection of Pancreatic Cancer.
PMID- 29966613
TI - Illuminating the Black Box: The Real Risk of Serious Infection With Inflammatory
Bowel Disease Therapies.
PMID- 29966612
TI - Misoprostol Heals Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding.
AB - BACKGROUND & AIMS: There is no effective treatment for aspirin-induced small
bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled
trial to determine whether misoprostol can heal small bowel ulcers in patients
with small bowel bleeding who require continuous aspirin therapy. METHODS: We
performed a prospective study of 84 aspirin users with small bowel bleeding who
required continued aspirin therapy in Hong Kong and Japan. Patients with small
bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly
assigned to groups that received either misoprostol (200 MUg, 4 times daily; n =
42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100
mg, once daily). The primary end point was complete ulcer healing at follow-up
capsule endoscopy. Secondary end points included changes in hemoglobin level and
number of ulcer/erosions from baseline. RESULTS: Complete healing of small bowel
ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%
42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%-18.4%), for a
difference in proportion of 19.0% (95% CI, 2.8%-35.3%; P = .026). The misoprostol
group had a significantly greater mean increase in hemoglobin than the placebo
group (mean difference, 0.70 mg/dL; 95% CI, 0.05-1.36; P = .035). The reduction
in medium number of ulcers or erosions was significantly greater in the
misoprostol group (from 6.5 [range, 1-85] to 2 [range, 0-25]) than in the placebo
group (from 7 [range, 1-29] to 4 [range, 0-19] (P = .005). CONCLUSIONS: In a
double-blind, randomized, placebo-controlled trial, we found misoprostol to be
superior to placebo in promoting healing of small bowel ulcers among aspirin
users complicated by small bowel ulcer bleeding who require continuous aspirin
therapy. However, use of misoprostol alone would provide only limited protection
against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776.
PMID- 29966614
TI - Acute hepatitis E in French patients and neurological manifestations.
AB - OBJECTIVES: Hepatitis E virus (HEV) is a major cause of acute hepatitis
worldwide. However, our understanding of the source of contamination is
incomplete and the frequency of neurological manifestations in still unknown.
METHODS: 200 eligible cases reported to the French National Reference Center from
January 2015 to December 2015 were prospectively included in this case-control
study (1 case: 1 control, matched for sex, age and area of living) to investigate
the risk of infection. We documented the factors associated with their HEV
infection and clinical manifestations. RESULTS: The 200 HEV-infected patients
included 137 who were immunocompetent and 63 immunocompromised. The factors
associated with an HEV infection were contact with farm animals, eating pork
liver sausage and eating unpeeled fruit. The 33 patients (16.5%) who reported
neurological symptoms included 14 with neuropathic pain suggesting small fiber
neuropathy, 9 with painless sensory disorders, 6 with Parsonage-Turner syndrome,
one Guillain-Barre syndrome, one meningitis, one encephalitis and one diplopia.
Neurological manifestations were more frequent in immunocompetent patients (22.6%
vs 3.2%, p < 0.001). CONCLUSIONS: This study highlights the risk of HEV
transmission by the environment in industrialized countries. The higher frequency
of neurological disorders in immunocompetent patients suggests pathophysiological
mechanisms involving the immune system.
PMID- 29966615
TI - Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets.
AB - Diabetic neuropathy is regarded as one of the most debilitating outcomes of
diabetes mellitus and may cause pain, decreased motility, and even amputation.
Diabetic neuropathy includes multiple forms, ranging from discomfort to death.
Prognosis of diabetic neuropathy is an uphill task as it remains silent for
several years after the onset of diabetes. Hyperglycemia, apart from inducing
oxidative stress in neurons, also leads to activation of multiple biochemical
pathways which constitute the major source of damage and are potential
therapeutic targets in diabetic neuropathy. A vast array of molecular pathways,
including polyol pathway, hexosamine pathway, PKCs signaling, oxidative stress,
AGEs pathway, PARP pathway, MAPK pathway, NF-kappaB signaling, hedgehog pathways,
TNF-alpha signaling, cyclooxygenase pathway, interleukins, lipoxygenase pathway,
nerve growth factor, Wnt pathway, autophagy, and GSK3 signaling may be accounted
for the pathogenesis and progression of diabetic neuropathy. Although symptomatic
treatment is available for diabetic neuropathy, few treatment options are
available to eliminate the root cause. The immense physical, psychological, and
economic burden of diabetic neuropathy highlights the need for cost effective and
targeted therapies. The main aim of this review is to highlight the putative role
of various mechanisms and pathways involved in the development of diabetic
neuropathy and to impart an in-depth insight on new therapeutic approaches aimed
at delaying or reversing various modalities of diabetic neuropathy.
PMID- 29966617
TI - TMS over right OFA affects individuation of faces but not of exemplars of
objects.
AB - In addition to its well-documented role in processing of faces, the occipital
face area in the right hemisphere (rOFA) may also play a role in identifying
specific individuals within a class of objects. Here we explored this issue by
using fMRI-guided TMS. In a first experiment, participants had to judge whether
two sequentially presented images of faces or objects represented exactly the
same exemplar or two different exemplars of the same class, while receiving
online TMS over either the rOFA, the right lateral occipital cortex (rLO) or the
Vertex (control). We found that, relative to Vertex, stimulation of rOFA impaired
individuation of faces only, with no effect on objects; in contrast, TMS over rLO
reduced individuation of objects but not of faces. In a second control experiment
participants judged whether a picture representing a fragment of a stimulus
belonged or not to the subsequently presented image of a whole stimulus (part
whole matching task). Our results showed that rOFA stimulation selectively
disrupted performance with faces, whereas performance with objects (but not with
faces) was selectively affected by TMS over rLO. Overall, our findings suggest
that rOFA does not contribute to discriminate between exemplars of non-face
objects.
PMID- 29966616
TI - Intracellular emetic signaling evoked by the L-type Ca2+ channel agonist FPL64176
in the least shrew (Cryptotis parva).
AB - Ca2+ plays a major role in maintaining cellular homeostasis and regulates
processes including apoptotic cell death and side-effects of cancer chemotherapy
including vomiting. Currently we explored the emetic mechanisms of FPL64176, an L
type Ca2+ channel (LTCC) agonist with maximal emetogenic effect at its 10 mg/kg
dose. FPL64176 evoked c-Fos immunoreactivity in shrew brainstem sections
containing the vomit-associated nuclei, nucleus tractus solitarius (NTS) and
dorsal motor nucleus of the vagus. FPL64176 also increased phosphorylation of
proteins ERK1/2, PKCalpha/betaII and Akt in the brainstem. Moreover, their
corresponding inhibitors (PD98059, GF 109203X and LY294002, respectively) reduced
FPL64176-evoked vomiting. A 30 min subcutaneous (s.c.) pretreatment with the LTCC
antagonist nifedipine (10 mg/kg) abolished FPL64176-elicited vomiting, c-Fos
expression, and emetic effector phosphorylation. Ryanodine receptors (RyRs) and
inositol trisphosphate receptors (IP3Rs) mediate intracellular Ca2+ release from
the sarcoplasmic/endoplasmic reticulum. The RyR antagonist dantrolene (i.p.), or
a combination of low doses of nifedipine and dantrolene, but not the IP3R
antagonist 2-APB, significantly attenuated FPL64176-induced vomiting. The
serotonin type 3 receptor (5-HT3R) antagonist palonosetron (s.c.), the neurokinin
1 receptor (NK1R) antagonist netupitant (i.p.) or a combination of non-effective
doses of netupitant and palonosetron showed antiemetic potential against FPL64176
evoked vomiting. Serotonin (5-HT) and substance P immunostaining revealed
FPL64176-induced emesis was accompanied by an increase in 5-HT but not SP
immunoreactivity in the dorsomedial subdivision of the NTS. These findings
demonstrate that Ca2+ mobilization through LTCCs and RyRs, and subsequent emetic
effector phosphorylation and 5-HT release play important roles in FPL64176
induced emesis which can be prevented by 5-HT3R and NK1R antagonists.
PMID- 29966618
TI - Validation of a simple, fast liquid chromatography-tandem mass spectrometry
method for the simultaneous quantification of 40 antidepressant drugs or their
metabolites in plasma.
AB - INTRODUCTION: Antidepressant (AD) use has increased significantly over the last
decades. Therapeutic drug monitoring is recommended for compliance, toxicity and
treatment efficiency. ADs also show a high prevalence in forensic cases. Few
methods have been developed that combine a fast, easy sample clean-up with a
quantification based on liquid chromatography-triple quadrupole mass spectrometry
(LC-QQQ). METHODOLOGY: A liquid-liquid extraction (LLE) was performed using 200
MUL of plasma. The evaporated and reconstituted upper fraction was injected on a
LC-QQQ system monitoring 3 transitions per compound. The method was fully
validated according to international guidelines. RESULTS & DISCUSSION: The
chromatographic run time was under 12 min. The LLE was successful in removing
interferences with minimal sensitivity loss. Calibration curves ranged from sub
therapeutic to toxic concentrations. Quality control samples showed high accuracy
(81%-119%) and precision (<=14%) within and between batches. Stability was tested
at ambient temperature and -20 degrees C. The method was successfully applied to
external quality control and case samples. CONCLUSION: The presented method
successfully quantifies 40 compounds of interest. Because of a simple sample
clean-up, a relatively short chromatographic run and a wide calibration range
this method can be implemented in therapeutic drug monitoring, forensic research
and related fields.
PMID- 29966619
TI - Soluble CD14 is associated with the structural failure of bioprostheses.
AB - INTRODUCTION: Aortic valve bioprostheses, which do not mandate chronic
anticoagulation, are prone to structural valve degeneration (SVD). The processes
involved in SVD are likely multifactorial. We hypothesized that inflammation and
macrophage activation could be involved in SVD. METHODS: In 203 patients with an
aortic valve bioprosthesis, we evaluated the association between the macrophage
activation marker soluble CD14 (sCD14) and SVD. RESULTS: After a mean follow-up
of 8 +/- 3 years, 42 (21%) patients developed SVD. Patients with SVD had higher
peak (44 +/- 13 mmHg vs. 25 +/- 12 mmHg, p < .0001) and mean (24 +/- 7 mmHg vs.
12 +/- 5 mmHg, p < .0001) transprosthetic gradients. On univariable analysis, low
density lipoprotein cholesterol (LDL) and sCD14 were associated with SVD. After
correction for covariates, sCD14 (OR: 1.12, 95%CI: 1.02-1.23, p = .01) remained
independently associated with SVD. In turn, sCD14 was associated with the HOMA
index and high-density lipoprotein (HDL) level. Patients with a metabolic
syndrome (MetS) had higher level of sCD14. In a model corrected for age, sex,
HOMA and HDL, the MetS remained independently associated with sCD14 levels (beta
= 0.65, SE = 0.30, p = .03). CONCLUSION: Circulating level of sCD14 is an
independent predictor of SVD. In turn, patients with MetS have higher sCD14
levels.
PMID- 29966620
TI - LC-ESI-MS/MS identification and characterization of ponatinib in vivo phase I and
phase II metabolites.
AB - Ponatinib (Iclusig(r)) is a multi-targeted tyrosine kinase inhibitor (TKIs). It
is active against T315I and other BCR-ABL mutants. Investigation of in vivo
metabolism of ponatinib was done using Sprague Dawley rats by giving one oral
dose of PNT (4.7 mg/kg) to each rat and urine samples were gathered at several
time intervals from dosing. Filteration of urine samples was done through 0.45
MUm syringe filters. Phase separation using ACN was applied for extraction of
ponatinib related metabolites. Characterization and identification of one in vivo
phase II metabolite and thirteen in vivo phase I of PNT were done using LC-MS/MS.
Phase I metabolic reactions were reduction, N-demethylation, hydroxylation, N
oxidation, oxidation and amide hydrolysis. Phase II metabolic reaction was
glucuronidation of hydroxyl benzyl metabolites of ponatinib. The major in vivo
metabolic reactions were alpha hydroxylation and alpha oxidation at piperazine
ring. Literature review revealed no articles that have been published on in vivo
metabolism of ponatinib in Sprague Dawley rats or ponatinib in vivo phase I and
phase II metabolites structural characterization and identification.
PMID- 29966621
TI - Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma.
AB - BACKGROUND: TEA domain transcription factor (TEAD) has an oncogenic role in
hepatocellular carcinoma (HCC). However, whether a membrane protein can serve not
only as a tumor marker that reflects TEAD function but also as a therapeutic
target that stimulates tumorigenesis in HCC remains unknown. METHODS: Tissue NRP1
was measured using immunohistochemistry. Cell viability, colony formation and
caspase3/7 activity were assessed using MTT, soft agar and caspase 3/7 Glo
assays, respectively. Serum NRP1 was examined using ELISA and Western blotting.
RESULTS: NRP1 expression was up-regulated by TEAD. We also identified a conserved
TEAD-binding motif in the NRP1 promoters, which was essential for the TEAD-NRP1
interaction. NRP1 was upregulated in HCC tissues and cell lines, and knockdown of
NRP1 inhibited the transformative phenotypes of HCC cells. Notably, the
concentrations of serum NRP1 in the HCC patients were much higher than those of
hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer
and lung cancer patients. Moreover, serum NRP1 was significantly associated with
AFP, gamma-GT, Alb, bile acid, ALT, AST, ALP and pre-Alb. The area under the
receiver operating characteristic curve (AUC-ROC) for serum NRP1 was 0.971,
presenting better diagnostic performance compared to AFP. CONCLUSIONS: NRP1 is a
novel tumor marker in HCC.
PMID- 29966622
TI - Glutamine-dependent lysosome homeostatic changes induced by starvation and
lysosome inhibition.
AB - Lysosomes are a major organelle for degrading macromolecules. When deprived of
nutrients, cells activate the autophagy and lysosome biogenesis pathways to
recycle cytoplasmic materials and to increase lysosomal degradation capacity for
survival, respectively. We have identified a condition in which cells accumulated
enlarged lysosomes upon starvation and lysosome inhibition. Selective autophagy
and inhibition of the mechanistic target of rapamycin (mTOR) in combination with
lysosome inhibition were not able to induce this phenomenon. Conversely, knocking
out autophagy genes, ATG5 or ATG7, had no effects on the enlarged lysosome
formation. This suggests that the enlarged lysosome formation is an autophagy
independent process. Remarkably, adding glutamine to the treatment can prevent
formation of the enlarged lysosomes and dissipate the pre-existing ones.
Furthermore, the nucleus/cytoplasm translocation of the transcription factor EB
(TFEB), but not mTOR activity, correlates with the formation/dissipation of
enlarged lysosomes. Knockdown of TFEB, however, suggests that TFEB-mediated
lysosome biogenesis is not directly involved in the process. These results
indicate that there is a novel mechanism by which lysosome homeostasis can be
regulated under certain stress conditions.
PMID- 29966623
TI - The Right Heart-Pulmonary Circulation Unit: Physiopathology.
AB - The most common cause of right heart failure is increased afterload caused by
pulmonary hypertension. Right ventricular function adaptation to increased
afterload is basically systolic, with secondary increase in dimensions and
systemic congestion. Increased right ventricular dimensions and decreased
ejection fraction are associated with a decreased survival in severe pulmonary
hypertension. Targeted therapies titrated to reverse the right ventricular
remodeling dimensions improve survival in severe pulmonary hypertension.
PMID- 29966624
TI - The Right Heart-Pulmonary Circulation Unit in Systemic Hypertension.
AB - Systemic hypertension is a risk factor for left heart failure, mostly with
preserved ejection fraction. Left heart failure is a cause of pulmonary
hypertension and eventual right ventricular (RV) failure. There has been report
of altered RV function in mild to moderate hypertension with preserved systolic
as well as diastolic function of the left ventricle. The pathophysiology of this
complication of hypertension is unclear. Preserving the RV and preventing the
development of pulmonary vascular disease may be considered among the targets of
optimized therapy for systemic hypertension.
PMID- 29966625
TI - Pulmonary Arterial Hypertension.
AB - This article provides an overview of pulmonary arterial hypertension (PAH),
beginning with the initial pathologic recognition of pulmonary hypertension more
than 100 years ago and progressing to the current diagnostic categorization of
PAH. It reviews the epidemiology, pathophysiology, genetics, and modern treatment
of PAH. The article discusses several important recent studies that have
highlighted the importance of new management strategies, including serial risk
assessment and combination pharmacotherapy.
PMID- 29966626
TI - Pulmonary Circulation on the Crossroads Between the Left and Right Heart in
Systemic Sclerosis: A Clinical Challenge for Cardiologists and Rheumatologists.
AB - Involvement of the right heart-pulmonary circulation system in systemic sclerosis
is a typical feature, with critical prognostic implications. Pulmonary
hypertension may occur in association with interstitial lung disease or as a
result of an isolated pulmonary vascular disease that may affect both the
precapillary arterioles and the postcapillary venules, as well as a consequence
of left heart involvement. These apparently different phenotypes often underlie a
significant pathophysiologic overlap, which makes the diagnosis and management of
these patients highly complex and uncertain.
PMID- 29966627
TI - Right Heart-Pulmonary Circulation Unit in Congenital Heart Diseases.
AB - The right ventricle plays a major role in congenital heart disease. This article
describes the right ventricular mechanics in some selected congenital heart
diseases affecting the right ventricle in different ways: tetralogy of Fallot,
Ebstein anomaly, and the systemic right ventricle.
PMID- 29966628
TI - Pulmonary Hypertension and Heart Failure: A Dangerous Liaison.
AB - Pulmonary hypertension (PH) is a common hemodynamic evolution of heart failure
(HF) with preserved or reduced ejection fraction, responsible for congestion,
symptoms worsening, exercise limitation, and negative outcome. In HF of any
origin, PH develops in response to a passive backward pressure transmission as
result of increased left atrial pressure. Sustained pressure injury and chronic
venous congestion can trigger pulmonary vasoconstriction and vascular remodeling,
leading to irreversible pulmonary vascular disease, right ventricular
hypertrophy, and failure. In this article, the key determinants of this
"dangerous liaison" are analyzed with some digressions on related "leitmotiv" at
the horizon.
PMID- 29966629
TI - Right Heart-Pulmonary Circulation Unit in Cardiomyopathies and Storage Diseases.
AB - Cardiomyopathies (CM) are a heterogeneous group of muscle heart diseases, divided
into 3 main categories (dilated, hypertrophic, and restrictive). In addition to
these subgroups, athlete's heart and hypertensive cardiopathy are both the result
of heart adaptation to increased loading conditions, making it possible to
include them in the CM group. Right heart involvement is clear in some CM as
arrhythmogenic CM, carcinoid syndrome, and endomyocardial fibrosis, whereas in
others, like hypertrophic or dilated CM, it is known that the right heart has a
prognostic impact but less clear is its pathogenic role.
PMID- 29966630
TI - Pulmonary Hypertension: The Role of Lung Transplantation.
AB - Despite advances in targeted medical therapy, pulmonary arterial hypertension
(PAH) remains a fatal disease because of progressive right ventricular
dysfunction. For patients who are refractory to medical therapy, heart-lung and
lung transplantation are important treatment options. Because of longer waiting
time, surgical interventions including extracorporeal lung support and atrial
septostomy can be used in PAH patients bridging to transplantation.
PMID- 29966631
TI - Right Heart-Pulmonary Circulation at High Altitude and the Development of
Subclinical Pulmonary Interstitial Edema.
AB - Most healthy subjects can develop a subclinical interstitial pulmonary edema that
is a complex and multifactor phenomenon, still with unanswered questions, and
might be one line of defense against the development of severe symptomatic lung
edema. Whether the acute, reversible increase in lung fluid content is really an
innocent and benign part of the adaptation to extreme physiologic condition or
rather the clinically relevant marker of an individual vulnerability to life
threatening high altitude pulmonary edema remains to be established in future
studies. Thus the question if encouraging more conservative habits to climb is
right or not remains open.
PMID- 29966632
TI - Chronic Thromboembolic Pulmonary Hypertension.
AB - Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct type of
pulmonary hypertensive disease, characterized by incomplete or abnormal
resolution of acute pulmonary embolism such that residual emboli become organized
and fibrotic. CTEPH can occur in patients without a prior history of venous
thromboembolism, and is diagnosed based on precapillary pulmonary hypertension on
right heart catheterization with evidence of chronic emboli on
ventilation/perfusion scan, chest imaging, or pulmonary angiogram. Pulmonary
endarterectomy (PEA) is often curative, and results in improved survival. In
patients for whom PEA is not feasible, medical therapy has been effective in
improving hemodynamics and functional capacity.
PMID- 29966633
TI - Invasive and Noninvasive Evaluation for the Diagnosis of Pulmonary Hypertension:
How to Use and How to Combine Them.
AB - The etiologic diagnosis of pulmonary hypertension (PH) may be very challenging.
Right-heart catheterization (RHC) in isolation cannot classify a precapillary PH
patient into group 1, 3, 4, or 5. Moreover, RHC may be not sufficient for
reaching a definitive differential diagnosis of precapillary or postcapillary PH
if hemodynamic data are not integrated in clinical context and combined with
information gleaned from noninvasive imaging. Therefore, only the integration of
risk factors, clinical evaluation, invasive and noninvasive tests allows the
physician to distinguish between different forms of PH.
PMID- 29966634
TI - Imaging the Right Heart-Pulmonary Circulation Unit: The Role of Ultrasound.
AB - Echocardiography is the first step in imaging the right heart pulmonary
circulation unit (RH-PCU), and the only one to allow its complete morphologic,
functional, and hemodynamic analysis in all clinical scenarios. Right ventricular
(RV) function is not only the consequence of its intrinsic contractile function
(morphology and contractility) but also highly dependent on preload, afterload,
and ventricular interdependence. Comprehensive echocardiographic examination of
RH-PCU allows insight into intrinsic and extrinsic factors of RV function. Newer
echocardiographic techniques allow for 3-dimensional evaluation of RV and
detailed measurements of regional function using tissue Doppler or speckle
tracking-based strain estimates.
PMID- 29966635
TI - Imaging the Right Heart-Pulmonary Circulation Unit: The Role of MRI and Computed
Tomography.
AB - The different components of the right heart pulmonary circulation unit can be
investigated by MRI and computed tomography. MRI has clear advantages over
echocardiography for accurate definition of right heart function and structure
and to derive functional information regarding the pulmonary vasculature.
Computed tomography is superior for the assessment of parenchymal and vascular
pathologies of the lung with indications in the diagnostic work-up of pulmonary
hypertension, but with more limited capability to evaluate right ventricular
function and in deriving pulmonary hemodynamics. Recent technical developments
with these imaging modalities could allow a better evaluation of the right heart
pulmonary circulation unit.
PMID- 29966636
TI - Biomarkers in Pulmonary Hypertension.
AB - Biomarkers are tools in pulmonary hypertension (PH) management. They may address
risk assessment, disease progression, response to medical and surgical therapy,
risk of right heart failure, and prognosis. The activation of molecular pathways
is the pathophysiological underpinning of the biomarkers assessed in peripheral
venous blood. A multiparametric approach, involving different biomarkers, is
preferred because it provides relevant clinical information regarding different
organs and body systems. This is especially true in the final stages of PH with
its comorbidities and different pathophysiological patterns, supporting that PH
is a systemic condition rather than an isolated cardiorespiratory illness.
PMID- 29966637
TI - Pulmonary Hypertension Related to Chronic Obstructive Pulmonary Disease and
Diffuse Parenchymal Lung Disease: A Focus on Right Ventricular (Dys)Function.
AB - Diffuse pulmonary lung disease and chronic obstructive pulmonary disease is a
heterogeneous population that can manifest pulmonary hypertension. These
subgroups are classified as primarily World Health Organization group 3.
Available data suggest that the impact of pulmonary hypertension targeted therapy
in diffuse pulmonary lung disease and chronic obstructive pulmonary disease is
limited and survival is poor despite attempted treatment.
PMID- 29966638
TI - Chronic Right Heart Failure: Expanding Prevalence and Challenges in Outpatient
Management.
AB - Right heart failure is caused by right heart dysfunction resulting in suboptimal
stroke volume to supply the pulmonary circulation. Therapeutic developments mean
that patients with acute right heart failure survive to hospital discharge and
live with chronic right heart failure. Chronic right heart failure management
aims to reduce afterload, optimize preload, and support contractility, with the
best evidence available in vascular targeted therapy for pulmonary arterial
hypertension. However, the management of chronic right heart failure relies on
adapting therapies for left ventricular heart failure to the right. We review
right heart failure management in the ambulatory setting and its challenges.
PMID- 29966639
TI - Exercise Training and Rehabilitation in Pulmonary Hypertension.
AB - Within the last years, exercise training and rehabilitation as add-on to medical
treatment has become an emerging field in pulmonary hypertension. Owing to the
beneficial effects of exercise training in pulmonary hypertension, the new
European Respiratory Society/European Society of Cardiology guidelines for
pulmonary hypertension recommended a supervised and closely monitored exercise
and respiratory training/rehabilitation as add-on to medical therapy (class IIa,
level of evidence B). In this article, different training modalities, effects of
exercise training, possible pathobiological mechanisms of action, and future
research questions are discussed.
PMID- 29966640
TI - The Right Heart-Pulmonary Circulation Unit and Left Heart Valve Disease.
AB - Valvular heart disease (VHD) is frequently accompanied by pulmonary hypertension
(PH). In asymptomatic patients, PH is rare, although the exact prevalence is
unknown and mainly stems from the severity of the VHD and the presence of
diastolic dysfunction. PH can also be depicted during exercise echocardiography.
PH either at rest or during exercise is also a powerful determinant of outcome
and is independently associated with reduced survival, regardless of the severity
of the underlying valvular pathology. Therefore, because PH is a marker of poor
prognosis, assessment of PH in VHD is crucial for risk stratification and
management of patients with VHD.
PMID- 29966642
TI - Right Heart Catheterization for the Diagnosis of Pulmonary Hypertension:
Controversies and Practical Issues.
AB - Right heart catheterization (RHC) is the gold standard for the diagnosis and
classification of pulmonary hypertension. Significant expertise is required for
safely performing a full RHC and for the acquisition of reliable and reproducible
information. Physicians performing an RHC should have adequate training not only
in vascular access, catheter insertion, and manipulation but also in the
interpretation of waveforms, potential pitfalls, and strict quality control. This
article describes the essential technical aspects of RHC as applied to the
pulmonary circulation, the potential pitfalls, and areas of major controversy.
PMID- 29966641
TI - The Right Heart International Network (RIGHT-NET): Rationale, Objectives,
Methodology, and Clinical Implications.
AB - The Right Heart International Network is a multicenter international study aiming
to prospectively collect exercise Doppler echocardiography tests of the right
heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects,
elite athletes, and individuals at risk of or with overt pulmonary hypertension.
It is going to provide standardization of exercise stress echocardiography of
RHPCU and explore the full physiopathologic response.
PMID- 29966643
TI - The RIGHT Heart International NETwork (RIGHT-NET): A Road Map Through the Right
Heart-Pulmonary Circulation Unit.
PMID- 29966644
TI - Erratum.
PMID- 29966645
TI - Social Competence Treatment After Traumatic Brain Injury: A Multicenter,
Randomized Controlled Trial of Interactive Group Treatment Versus Noninteractive
Treatment.
AB - OBJECTIVE: To evaluate the effectiveness of a replicable group treatment program
for improving social competence after traumatic brain injury (TBI). DESIGN:
Multicenter randomized controlled trial comparing 2 methods of conducting a
social competency skills program, an interactive group format versus a classroom
lecture. SETTING: Community and veteran rehabilitation centers. PARTICIPANTS:
Civilian, military, and veteran adults with TBI and social competence
difficulties (N=179), at least 6 months postinjury. INTERVENTIONS: The
experimental intervention consisted of 13 weekly group interactive sessions
(1.5h) with structured and facilitated group interactions to improve social
competence, and the control consisted of 13 traditional classroom sessions using
the same curriculum with brief supplemental individual sessions but without
structured group interaction. MAIN OUTCOME MEASURES: Profile of Pragmatic
Impairment in Communication (PPIC), an objective behavioral rating of social
communication impairments after TBI. LaTrobe Communication Questionnaire (LCQ),
Goal Attainment Scale (GAS), Satisfaction with Life Scale, Posttraumatic Stress
Disorder Checklist-C (PCL) civilian version, Brief Symptom Inventory 18 (BSI-18),
Scale of Perceived Social Self-Efficacy (PSSE). RESULTS: Social competence goals
(GAS) were achieved and maintained for most participants regardless of treatment
method. Significant improvements in the primary outcome (PPIC) and 2 of the
secondary outcomes (LCQ and BSI) were seen immediately posttreatment and at 3
months posttreatment in the alternative treatment arm only; however, these
improvements were not significantly different between the group interactive
structured treatment and alternative treatment arms. Similar trends were observed
for PSSE and PCL-C. CONCLUSIONS: Social competence skills improved for persons
with TBI in both treatment conditions. The group interactive format was not found
to be a superior method of treatment delivery in this study.
PMID- 29966646
TI - Coping Flexibility as Predictor of Distress in Persons With Spinal Cord Injury.
AB - OBJECTIVES: Examine whether coping flexibility at admission to first spinal cord
injury (SCI) rehabilitation was predictive of distress 1 year after discharge.
DESIGN: Longitudinal inception cohort study. SETTING: Rehabilitation center.
PARTICIPANTS: Of the 210 people admitted to their first inpatient SCI
rehabilitation program, 188 met the inclusion criteria. n=150 (80%) agreed to
participate; the data of participants (N=113) with a complete dataset were used
in the statistical analysis. INTERVENTIONS: Not applicable. MAIN OUTCOME
MEASURES: Coping flexibility was operationalized by (1) flexible goal adjustment
(FGA) to given situational forces and constraints and (2) tenacious goal pursuit
(TGP) as a way of actively adjusting circumstances to personal preference. The
Assimilative-Accommodative Coping Scale was used to measure FGA and TGP. The
Hospital Anxiety and Depression Scale was used to assess distress. RESULTS:
Scores on FGA and TGP measured at admission were negatively associated with the
scales depression (r= -.33 and -.41, respectively) and anxiety (r= -.23 and -.30,
respectively) 1 year after discharge. All demographic and injury-related
variables at admission together explained a small percentage of the variance of
depression and anxiety. FGA, TGP, and the interaction term together explained a
significant additional 16% of the variance of depression and 10% of anxiety.
CONCLUSIONS: The tendency to pursue goals early postonset of the injury seems to
have a protecting effect against distress 1 year after discharge. People with low
TGP may experience protection against distress from high FGA.
PMID- 29966647
TI - The Development of a New Computer-Adaptive Test to Evaluate Strain in Caregivers
of Individuals With TBI: TBI-CareQOL Caregiver Strain.
AB - OBJECTIVE: To develop a new measure of caregiver strain for use in caregivers of
individuals with traumatic brain injury (TBI), Traumatic Brain Injury Caregiver
Quality of Life (TBI-CareQOL) Caregiver Strain. DESIGN: Qualitative data,
literature reviews, and cross-sectional survey study. SETTING: Three TBI Model
Systems rehabilitation hospitals, an academic medical center, and a military
medical treatment facility. PARTICIPANTS: Caregivers (N=560) of civilians (n=344)
or service members/veterans (SMVs) with TBI (n=216). INTERVENTIONS: Not
applicable. MAIN OUTCOME MEASURE: TBI-CareQOL Caregiver Strain Item Bank.
RESULTS: Exploratory and confirmatory factor analyses, a graded response model
(GRM) and differential item functioning supported the retention of 33 items in
the final measure. GRM calibration data was used to inform the selection of a 6
item static short form, and to program the TBI-CareQOL Caregiver Strain computer
adaptive test (CAT). CAT simulation analyses indicated a 0.97 correlation between
the CAT scores and the full item-bank. Three-week test-retest reliability was
strong (r=0.83). CONCLUSIONS: The new TBI-CareQOL Caregiver Strain CAT and
corresponding 6-item short form were developed using established rigorous
measurement development standards; this is the first self-reported measure
developed to evaluate caregiver strain in caregivers of individuals with TBI.
PMID- 29966648
TI - Understanding Health-Related Quality of Life in Caregivers of Civilians and
Service Members/Veterans With TBI: Reliability and Validity Data for the TBI
CareQOL Measurement System.
AB - OBJECTIVES: To establish the reliability and validity of the newly developed TBI
CareQOL patient-reported outcome (PRO) measures in caregivers of civilians and
service members/veterans (SMVs) with traumatic brain injury (TBI) so that they
can be used with confidence in clinical research and practice. DESIGN: Computer
based surveys delivered through an on-line data capture platform. SETTING: Three
TBI Model Systems rehabilitation hospitals, an academic medical center, and a
military medical treatment facility. PARTICIPANTS: Caregivers (N=560) of
individuals with TBI; this included 2 different study samples: 344 caregivers of
civilians with TBI and 216 caregivers of SMVs with TBI. INTERVENTION: Not
Applicable. MAIN OUTCOME MEASURES: Five Traumatic Brain Injury Caregiver Quality
of Life (TBI-CareQOL) item banks. RESULTS: Reliabilities for the TBI-CareQOL
measures were excellent (all Cronbach's alpha >.88); 3-week test-retest
reliability ranged from .75 to .90 across the 2 samples. Convergent validity was
supported by moderate to high associations among the TBI-CareQOL measures and
moderate correlations between the TBI-CareQOL measures and other measures of
health-related quality of life (HRQOL) and caregiver burden. Discriminant
validity was supported by low correlations between the TBI-CareQOL measures and
less-related constructs (eg, caregiver satisfaction). Known-groups validity was
supported: caregivers of individuals that were low functioning had worse HRQOL
than caregivers of high-functioning individuals. CONCLUSIONS: Results provide
psychometric support for the new TBI-CareQOL item banks. As such, these measures
fill a significant gap in the caregiver literature where sensitive PRO measures
that capture changes in HRQOL are needed to detect improvements for interventions
designed to assist family caregivers.
PMID- 29966649
TI - A Systematic Critical Appraisal of Evidence-Based Clinical Practice Guidelines
for the Rehabilitation of Children With Moderate or Severe Acquired Brain Injury.
AB - OBJECTIVE: The aim of this review was to critically appraise the quality of
evidence-based clinical practice guidelines (CPGs) for the rehabilitation of
children with moderate or severe acquired brain injury (ABI). DATA SOURCES: A
systematic search of MEDLINE, PsycINFO, Embase, CINAHL, and the Cochrane Library
was conducted and an extensive website search of prominent professional
rehabilitation society websites. STUDY SELECTION: CPGs were eligible for
inclusion if they incorporated recommendation statements for inpatient and/or
community rehabilitation for children with ABI and they were based on a
systematic evidence search. DATA EXTRACTION: Methodological quality of eligible
CPGs were appraised by 3 independent reviewers using the AGREE II instrument.
Characteristics of eligible CPGs and strength of supporting evidence for included
recommendations were extracted. DATA SYNTHESIS: Of the 9 included guidelines, 2
covered all ABIs, 5 focused specifically on traumatic brain injury, and 2 on
stroke. Five of the CPGs were classified as high quality and 4 were of average
quality. In general, CPGs scored better for scope and purpose, rigor of
development, and clarity of presentation. They scored most poorly in
applicability, involvement of target users, and procedures for updating the
guidelines. Interrater reliability for the AGREE II was generally high across
domains. Very few of the 445 recommendations included across the 9 CPGs were
evidence based. CONCLUSIONS: Despite variability in quality of the guideline
development process, the included CPGs generally provided clear descriptions of
their overall objectives, scope and purpose, employed systematic methods for
searching, selecting, and appraising research evidence, and produced unambiguous,
clearly identifiable recommendations for children with ABI. Overall, existing
CPGs focusing on rehabilitation for children with ABI are based on low-quality
evidence or expert consensus. Future work should focus on addressing the
limitations of most of the current CPGs, particularly related to supporting
implementation and integrating stakeholder involvement.
PMID- 29966650
TI - PB1 and UBA domains of p62 are essential for aggresome-like induced structure
formation.
AB - ALIS are large, transient, cytosolic aggregates that serve as storage
compartments for ubiquitin-tagged defective ribosomal products. We determined the
importance of the protein p62 in the formation of ALIS and demonstrated that two
domains of p62-PB1 and UBA-are essential for ALIS assembly. Those two major
binding domains of p62, also known as sequestosome 1, were shown to play a
critical role in the formation of autophagosomes or cytoplasmic aggregates.
Specifically, the PB1 domain is essential for self-oligomerization, and the UBA
domain allows p62 to bind to polyubiquitin chains or ubiquitinated proteins.
After stimulation of RAW 264.7 macrophages with lipopolysaccharide, we observed a
significant decrease in the number of cells with ALIS. Importantly, cells
overexpressing either a PB1 mutant or UBA-deleted p62 construct also exhibited a
substantially diminished number of cells containing ALIS. Since both p62 and
ubiquitin are found in ALIS, we evaluated the dynamics of YFP-tagged p62 in ALIS.
In contrast to the findings of a previous study that evaluated GFP-tagged
ubiquitin motility in ALIS, we determined that YFP-tagged p62 has very limited
mobility. Lastly, we determined that GST-tagged full-length p62 binds to Lys-63
linked polyubiquitin chains but not to Lys-48-linked chains. Overall, our
findings provide insight on the essential role that p62, particularly its PB1 and
UBA domains, has in the formation of ALIS.
PMID- 29966651
TI - Stable plastid transformation of rice, a monocot cereal crop.
AB - Rice is one of the most important cereal crops and its biotechnology has been
pursued to meet the food demand of ever-growing global population. Rice plastid
transformation has been a great challenge to achieve homoplastomic plants due to
its low efficiency of regeneration. In this experiment, Japonica rice line 19 was
chosen to be the receptor for plastid transformation. A vector harboring smGFP
gene was constructed and transferred into rice plastid genome by bombardment. The
resistant callus was obtained after long-lasting multiple selections and proved
to be in homoplastomic status by molecular testing. The plantlet was regenerated
from homoplastomic callus and grown to seeding stage. This is the first case so
far to achieve the homoplastomic rice and will be helpful to transform plastid
genome of monocotyledonous crops with recalcitrant nature.
PMID- 29966652
TI - The interaction of TraW and TrbC is required to facilitate conjugation in F-like
plasmids.
AB - Bacterial conjugation, such as that mediated by the E. coli F plasmid, is a main
mechanism driving bacterial evolution. Two important proteins required for F
pilus assembly and DNA transfer proficiency are TraW and TrbC. As members of a
larger complex, these proteins assemble into a type IV secretion system and are
essential components of pore formation and mating pair stabilization between the
donor and the recipient cells. In the current report, we demonstrate the physical
interaction of TraW and TrbC, show that TraW preferentially interacts with the N
terminal domain of TrbC, and that this interaction is important in restoring
conjugation in traW/trbC knockouts.
PMID- 29966653
TI - SPATULA regulates floral transition and photomorphogenesis in a PHYTOCHROME B
dependent manner in Arabidopsis.
AB - Light is the most important exogenous stimulus regulating plant growth and
various developmental processes. Phytochromes, especially PHYTOCHROME B (PHYB)
mediates the various light-mediated processes in Arabidopsis. SPATULA (SPT) is an
important transcription factor, which has been reported previously to participate
in temperature-mediated transition from seed dormancy to germination. Here we
investigate the function of SPT in the floral transition under long day
conditions and photomorphogenesis in Arabidopsis. In this study, spt-2 shows
significantly delayed flowering time. But mutation of SPT in the background of
phyb-1 rescues the phenotype of spt-2. The flowering time of double mutant of spt
2/phyb-1 is similar with the wild type. These results indicate that SPT promotes
the transition from vegetative stage to floral stage and it regulates this
transition in a PHYB-dependent manner. With qRT-PCR analysis, it is found that
SPT regulates flowering time via FLC, SVP, FT and SOC1. Furthermore, SPT also
controls photomorphogenesis. spt-2 displays shortened hypocotyls and increased
chlorophylls contents compared with the wild type. These phenotypes are also
rescued in the double mutant of spt-2/phyb-1. These results indicate that SPT is
also involved in photomorphogenic development in Arabidopsis and SPT regulates
photomorphogenesis in a PHYB-dependent manner. Collectively, SPT is not only a
temperature responder but it is also an important light regulator during plant
growth and development.
PMID- 29966654
TI - l-asparaginase induces intrinsic mitochondrial-mediated apoptosis in human
gastric adenocarcinoma cells and impedes tumor progression.
AB - l-asparagine essentially regulates growth and proliferation of cancer cells. l
asparaginase is an anti-cancer enzyme that deprives the cancer cells of l
asparagine. The purpose of this study was to explore the mechanism of a novel l
asparaginase from Pseudomonas fluorescens on l-asparagine deprivation mediated
anti-proliferation, apoptosis in human gastric adenocarcinoma cells and to
evaluate inhibition of angiogenesis. We observed that, the presence of
extracellular l-asparagine was essential for the growth of AGS cells. l
asparagine deprivation by l-asparaginase induced metabolic stress, cytotoxicity
and apoptosis by G0 phase cell-cycle arrest, modulated the mitochondrial membrane
integrity, accelerated caspase-3 activation and instigated DNA damage. The RT-PCR
analysis of pro-apoptosis genes: bak1, bax, bbc3, bik, pmaip1, bnip3l, apaf1,
casp3, casp7 and casp9 were significantly higher (P < 0.05), while anti-apoptotic
markers xiap, bid, mcl1, and death receptor genes tnf and tradd were
significantly down-regulated (P < 0.05). Additionally, higher protein expressions
of p53, caspase-3 and TEM analysis showing modulations in mitochondria confirmed
intrinsic apoptosis pathway. The enzyme impeded tumor progression through
inhibition of cell migration and vascular remodelling of endothelial cells. Our
findings suggests that the action of l-asparaginase alters mitochondrial membrane
permeability and auxiliary activates intrinsic apoptosis. Therefore, this
mechanistic approach might be considered as a targeted enzymotherapy against
gastric adenocarcinoma.
PMID- 29966655
TI - Long non-coding RNA KCNQ1OT1 modulates oxaliplatin resistance in hepatocellular
carcinoma through miR-7-5p/ ABCC1 axis.
AB - The underlying functions of long non-coding RNAs (lncRNAs) on chemoresistance in
multiple cancers have been testified. However, the function and mechanism of
lncRNAs on chemoresistance in hepatocellular carcinoma are still confused. In
this study, we concentrated on the function and mechanism of KCNQ1OT1 on
oxaliplatin resistance in hepatocellular carcinoma. Results showed that KCNQ1OT1
was significantly up-regulated in oxaliplatin-resistant HepG2 and Huh7 cells.
Moreover, knockdown of KCNQ1OT1 inhibited the cell proliferation, migration,
invasion and reduced the expression of drug-resistant gene (MRP5, MDR1, LRP1).
Additionally, bioinformatics analysis and dual-luciferase reporter assay showed
that miR-7-5p directly targeted the 3'-UTR of miR-7-5p and ABCC1 mRNA, indicating
that KCNQ1OT1 regulated the expression of ABCC1 via endogenous sponging miR-7-5p.
Conclusively, KCNQ1OT1 modulated oxaliplatin resistance in hepatocellular
carcinoma through miR-7-5p/ABCC1 axis, indicating a novel approach for the
treatment of hepatocellular carcinoma.
PMID- 29966656
TI - Withaferin A induces apoptosis by ROS-dependent mitochondrial dysfunction in
human colorectal cancer cells.
AB - Withaferin A (WA) is an active steroidal lactone derived from the herbal plant
Withania somnifera, which exhibits antitumor activity with reactive oxygen
species (ROS) modulating in a variety of cancer models, such as breast cancer,
lung cancer and pancreatic cancer. However, to the best of our knowledge, the
direct effect and mechanism of WA on CRC cells has not been previously
determined. The present study investigated the anti-tumor effects of WA on CRC
cells in vitro, and explored the mechanisms of action. The flow cytometry was
applied for detecting the accumulation of ROS with the treatment of withaferin A.
We performed the flow cytometry and western blot to evaluate the withaferin A
induced apoptosis and cell cycle arrest in human colon cancer cells. And to
verify the ROS accumulation induced mitochondrial dysfunction after the treatment
of withaferin A, fluorescence microscope and western blot were applied. WA
exerted a dose-dependent cytotoxic effect on HCT-116 and RKO cells. The effect
was associated with ROS-mediated cell cycle arrest and the expression of
apoptotic proteins. In addition, WA promoted ROS production and decreased
mitochondrial membrane potential accompanying with mitochondrial dysfunction.
Taken together, these results strongly indicated that WA directly inhibits cell
growth and induces apoptosis in CRC cells through ROS-mediated mitochondrial
dysfunction and JNKs pathway, and WA may be a promising potential candidate for
therapeutic application of CRC.
PMID- 29966657
TI - Upregulation of lncRNA VDR/CASC15 induced by facilitates cardiac hypertrophy
through modulating miR-432-5p/TLR4 axis.
AB - Sustained cardiac hypertrophy has threatened human health. With the development
of human genome project, non-coding RNAs (ncRNAs) have attracted more and more
attentions of researchers. As a subgroup of ncRNAs, long non-coding RNAs
(lncRNAs) has been widely studied in human diseases, including cardiac
hypertrophy. According to search results of bioinformatics website, lncRNA CASC15
potentially participates in the course of cardiac hypertrophy. According to the
result of qRT-PCR, CASC15 expression was upregulated when cardiomyocytes were
treated with Ang-II. Moreover, CASC15 was highly expressed in cardiac
hypertrophic model. Upregulation of CASC15 was accompanied with some hypertrophic
responses. To explore the specific biological function of CASC15 in cardiac
hypertrophy, loss-of-function experiments were conducted in Ang-II-induced
cardiomyocytes. Results of immunofluorence staining revealed that cell surface
area enlarged by Ang-II was decreased when CASC15 was silenced. The expression
levels of hypertrophic factors were attenuated by knockdown of CASC15. To detect
the molecular mechanism by which CASC15 regulates the progression of cardiac
hypertrophy, mechanism experiments were designed and carried out. It was found
that CASC15 was activated by the transcription factor VDR. Furthermore, CASC15
can upregulate TLR4 by competitively binding miR-432-5p. In conclusion,
Upregulation of lncRNA CASC15 induced by VDR facilitates cardiac hypertrophy via
miR-432-5p/TLR4 axis.
PMID- 29966658
TI - The effect of ghrelin O-acyltransferase inhibitor on gastric H+-K+-ATPase
activity and GOAT/ghrelin system in gastric mucosal cells in vitro.
AB - Ghrelin is implicated in the regulation of gastric functional development. The
octanoylation of ghrelin is critical for its physiological functions which
dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. To investigate the
effect of GOAT on gastric acid secretion and expression of ghrelin in vitro.
Primary cultures of gastric mucosal cells were challenged with 1.5 * 10-5, 1.5 *
10-4 and 1.5 * 10-3 mol/mL GO-CoA-Tat (The GOAT inhibitor), respectively, for 24
h in order to further clarify the effect of GOAT on H+-K+-ATPase activity. In
vitro, GO-CoA-Tat significantly increased ghrelin and GOAT mRNA expression at 1.5
* 10-5, 1.5 * 10-4 and 1.5 * 10-3 mol/mL, and augmented cell total ghrelin
secretion at 1.5 * 10-3 mol/mL. But cell acylated ghrelin secretion was reduced
at 1.5 * 10-3 mol/mL GO-CoA-Tat (P < 0.05). And cell acylated ghrelin synthesis
was reduced at 1.5 * 10-4 and 1.5 * 10-3 mol/mL GO-CoA-Tat (P < 0.05). In
accordance with acylated ghrelin level, H+-K+-ATPase activity were decreased with
1.5 * 10-4 and 1.5 * 10-3 mol/mL GO-CoA-Tat (P < 0.05). These results indicated
that GOAT inhibitor decreases the acylated ghrelin level and H+-K+-ATPase
activity in vitro.
PMID- 29966659
TI - Molecular cloning of vitellogenin gene promoters and in vitro and in vivo
transcription profiles following estradiol-17beta administration in the cutthroat
trout.
AB - Transcription of vitellogenin (vtg) genes are initiated when estradiol-17beta
(E2)-estrogen receptor (ER) complexes bind estrogen response elements (ERE)
located in the gene promoter region. Transcriptional regulation of dual vtg
subtypes (major salmonid A-type vtg: vtgAs; minor C-type vtg: vtgC) by E2 was
investigated under co-expression of a potential major transcriptional factor,
eralpha1, in cutthroat trout. Two forms of trout vtgAs promoters (1 and 2) and
one vtgC promoter were sequenced. These promoters structurally differ based on
the number of EREs present. The vtgAs promoter 1 exhibited the highest maximal
transcriptional activity by in vitro gene reporter assays. The concentration of
E2 that induces 50% of gene reporter activity (half-maximal effective
concentrations, EC50) was similar among all vtg promoters and also to the EC50 of
E2 administered to induce vtg transcription in vivo. This study revealed a
difference in transcriptional properties of multiple vtg promoters for the first
time in a salmonid species, providing the basis to understand mechanisms
underlying regulation of vitellogenesis via dual vtg gene expression.
PMID- 29966660
TI - Characterization of spermatogonial cells and niche in the scorpion mud turtle
(Kinosternon scorpioides).
AB - Undifferentiated spermatogonia (Aund) or spermatogonial stem cells (SSCs) are
committed to the establishment and maintenance of spermatogenesis and fertility
throughout a male's life and are located in a highly specialized microenvironment
called niche that regulates their fate. Although several studies have been
developed on SSCs in mammalian testis, little is known about other vertebrate
classes. The present study is the first to perform a more detailed investigation
on the spermatogonial cells and their niche in a reptilian species. Thus, we
characterized Aund/SSCs and evaluated the existence of SSCs niche in the
Kinosternon scorpioides, a freshwater turtle found from Mexico to northern and
central South America. Our results showed that, in this species, Aund/SSCs
exhibited a nuclear morphological pattern similar to those described for other
mammalian species already investigated. However, in comparison to other
spermatogonial cell types, Aund/SSCs presented the largest nuclear volume in this
turtle. Similar to some mammalian and fish species investigated, both GFRA1 and
CSF1 receptors were expressed in Aund/SSCs in K. scorpioides. Also, as K.
scorpioides Aund/SSCs were preferentially located near blood vessels, it can be
suggested that this niche characteristic is a well conserved feature during
evolution. Besides being valuable for comparative reproductive biology, our
findings represent an important step towards the understanding of SSCs biology
and the development of valuable systems/tools for SSCs culture and
cryopreservation in turtles. Moreover, we expect that the above-mentioned results
will be useful for reproductive biotechnologies as well as for governmental
programs aiming at reptilian species conservation.
PMID- 29966662
TI - Effects of NLRP6 on the proliferation and activation of human hepatic stellate
cells.
AB - Nod-like receptor pyrin domain-containing proteins (NLRPs) are known to take part
in the pathogenesis of chronic liver diseases, including liver fibrosis. However,
no known direct role of NLRP6, a member of NLRPs, has been reported in liver
fibrosis. Here, we found that NLRP6 expression was decreased in fibrotic and
cirrhotic livers. In a human hepatic stellate cell line, LX-2, overexpression of
NLRP6 suppressed cell proliferation, hydroxyproline accumulation, as well as the
expression of type I and type III collagens (Col-I and Col-III), alpha-smooth
muscle actin (alpha-SMA) and matrix metalloproteinases (MMP2 and MMP9), whereas
NLRP6 knockdown displayed reverse effects. Furthermore, NLRP6 significantly
suppressed the phosphorylation of Smad2/3 (p-Smad2/3) and enhanced the expression
of protein phosphatase magnesium dependent 1 A (PPM1A), the only phosphatase for
Smad2/3. NLRP6 overexpression abrogated TGF-beta1-stimulated hydroxyproline
accumulation and p-Smad2/3. Co-immunoprecipitation assay demonstrated that NLRP6
was able to form a complex with PPM1A. NLRP6 overexpression did not change the
level of p-Smad2/3 in LX-2 cells with PPM1A knockdown. These data indicated that
PPM1A was required for the inhibitory effects of NLRP6 on TGF-beta1/Smad2/3
signaling. In conclusion, our results suggest that NLRP6 exerts anti-fibrotic
effects in LX-2 cells via regulating PPM1A/Smad2/3 and that NLRP6 may be an
effective target in the treatment of liver fibrosis.
PMID- 29966661
TI - Nicotine induces oral dysplastic keratinocyte migration via fatty acid synthase
dependent epidermal growth factor receptor activation.
AB - Despite advances in diagnostic and therapeutic management, oral squamous cell
carcinoma (OSCC) patient survival rates have remained relatively unchanged. Thus,
identifying early triggers of malignant progression is critical to prevent OSCC
development. Traditionally, OSCC initiation is elicited by the frequent and
direct exposure to multiple tobacco-derived carcinogens, and not by the nicotine
contained in tobacco products. However, other nicotine-containing products,
especially the increasingly popular electronic cigarettes (e-cigs), have unknown
effects on the progression of undiagnosed tobacco-induced oral premalignant
lesions, specifically in regard to the effects of nicotine. Overexpression of
fatty acid synthase (FASN), a key hepatic de novo lipogenic enzyme, is linked to
poor OSCC patient survival. Nicotine upregulates hepatic FASN, but whether this
response occurs in oral dysplastic keratinocytes is unknown. We hypothesized that
in oral dysplastic keratinocytes, nicotine triggers a migratory phenotype through
FASN-dependent epidermal growth factor receptor (EGFR) activation, a common pro
oncogenic event supporting oral carcinogenesis. We report that in oral dysplastic
cells, nicotine markedly upregulates FASN leading to FASN-dependent EGFR
activation and increased cell migration. These results raise potential concerns
about e-cig safety, especially when used by former tobacco smokers with occult
oral premalignant lesions where nicotine could trigger oncogenic signals commonly
associated with malignant progression.
PMID- 29966663
TI - IL-1beta directly inhibits milk lipid production in lactating mammary epithelial
cells concurrently with enlargement of cytoplasmic lipid droplets.
AB - Mammary epithelial cells (MECs) in lactating mammary glands produce milk lipid,
which provides a large percentage of calories and bioactive lipids for
appropriate infant growth. However, secreted milk lipid is often reduced
concurrently with increases in IL-1beta, IL-6, and TNF-alpha in mammary glands
with mastitis. In this study, we investigated whether those cytokines directly
influenced lipid production and secretion. A lactating MEC culture model with
high lipid production ability was prepared by culture with oleic acid. TNF-alpha,
IL-1beta, and IL-6 differentially affected lipid production and secretion in
lactating MECs. In particular, IL-1beta treatment significantly reduced amounts
of secreted triglycerides by 97% compared with the control concurrently with
enlargement of cytoplasmic lipid droplets in MECs. IL-1beta also decreased mRNA
expression of Fabp3 and Srebp1 and the amount of aquaporin 3, GLUT-1 and
adipophilin in the milk lipid production pathway. Furthermore, IL-1beta
inactivated STAT5 and glucocorticoid signaling to induce milk production in MECs,
whereas STAT3 and NFkappaB signaling was activated. IL-1beta induced mRNA
expression of IL-6 and TNF-alpha in MECs. Therefore, we suggest that IL-1beta is
a key inhibitor of lipid production and secretion in lactating MECs.
PMID- 29966664
TI - ADAM17 promotes cell migration and invasion through the integrin beta1 pathway in
hepatocellular carcinoma.
AB - ADAM17 is believed to promote tumor development by facilitating both cell
proliferation and migration. In this study, we investigated the involvement of
ADAM17 and the activation of the integrin pathway in the regulation of the
malignant properties of hepatocellular carcinoma cells and tissues. ADAM17 was
positively correlated with active integrin beta1, which was determined using a
human tissue microarray and an N-nitrosodiethylamine-induced HCC mouse model. We
found elevated ADAM17 and active integrin beta1 levels in HCC tissues compared
with adjacent liver tissues, and the active integrin beta1 levels were associated
with tumor size and TNM grade. High ADAM17 and active integrin beta1 levels in
tumor tissues were significantly associated with poor survival of HCC patients.
RNAi-mediated ADAM17 knockdown and integrin beta1 blockade significantly
attenuated the migration and invasion of HCC cells, and overexpression of ADAM17
showed the reverse effects. ADAM17 interference attenuated the intrahepatic
growth and metastasis of HCC cells in an orthotopic xenograft model. ADAM17
knockdown cells showed diminished levels of active integrin beta1, p-FAK, p-AKT,
MMP-2 and MMP-9. ADAM17 knockdown significantly attenuated the translocation of
the Notch1 intracellular domain into the nucleus, whereas overexpression of the
Notch1 intracellular domain rescued the translocation and enhanced the activation
of integrin beta1. Our data provide evidence for ADAM17 as an important
determinant of malignant properties via regulation of integrin beta1 activation
and Notch1 signaling. Inhibition of ADAM17 may provide viable therapeutic
potential for preventing HCC metastasis.
PMID- 29966665
TI - Effect of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung
Transplantation Outcome.
AB - BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an
expected median survival of 3 months. Lung transplantation is a potentially
lifesaving therapy for AE-IPF. However, the current knowledge of transplantation
outcomes during AE-IPF is limited to a few small retrospective studies, reporting
only 1-year post-transplantation survival. METHODS: Study population included
patients with IPF consecutively listed for lung transplantation at a single
institution between the years 2012 and 2016. We collected lung allocation score
(LAS), hospitalization, and survival data. The primary outcome was survival among
patients transplanted during stable IPF vs during AE-IPF. RESULTS: Of 89 patients
with IPF listed for lung transplantation, 52 were transplanted during stable IPF
and 37 were hospitalized due to AE-IPF. Of these 37 patients, nine died before
transplantation, and 28 were transplanted during AE-IPF. Fifty percent of
patients transplanted during AE-IPF died in a mean follow-up of 1.6 +/- 1.2 years
compared with 12% of patients transplanted during stable IPF who died in a mean
follow-up of 2.6 +/- 1.2 years. The Kaplan-Meier survival curves post
transplantation after 1 and 3 years for patients who were transplanted during
stable IPF were 94% and 90% vs 71% and 60% in patients who were transplanted
during AE-IPF (P = .0001). LAS above 80 conferred a 3-year hazard ratio for
mortality of 5.7 vs LAS lower than 80 (95% CI, 2.33-14.0; P < .0005).
CONCLUSIONS: Patients with IPF transplanted during AE-IPF had significantly worse
short-term and long-term survival compared with patients transplanted during
stable IPF. Patients with AE-IPF and very high LAS may not experience the
survival advantage expected from lung transplantation.
PMID- 29966666
TI - Axon and Schwann Cell Degeneration in Nerves of Upper Airway Relates to
Pharyngeal Dysfunction in Snorers and Patients With Sleep Apnea.
AB - BACKGROUND: The pathophysiologic mechanism of nocturnal obstruction and
swallowing dysfunction commonly occurring in patients with sleep apnea is
unclear. The goal of this study was to investigate whether nerve injuries in the
upper airways of snorers and patients with sleep apnea are associated with
pharyngeal dysfunction and severity of sleep apnea. METHODS: Twenty-two patients
undergoing palatal surgery due to snoring and sleep apnea were investigated for a
swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring
subjects were included as control subjects. Tissue samples from the soft palate
at the base of the uvula were obtained in all patients and control subjects.
Nerves and muscle were analyzed with immunohistochemical and morphologic methods,
and the findings were correlated with swallowing function and degree of sleep
apnea. RESULTS: In the soft palate of patients, nerve fascicles exhibited a
significantly lower density of axons (5.4 vs 17.9 * 10-3 axons/MUm2; P = .02), a
smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and
a larger number of circular shaped Schwann cells lacking central axons (43.0% vs
12.7%; P < 0.001) compared with control subjects. The low density of axons was
significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and
apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed
in patients compared with control subjects (11.3 +/- 4.2% vs 4.8 +/- 2.4%; P =
.02). CONCLUSIONS: Axon degeneration in preterminal nerves of the soft palate is
associated with pharyngeal dysfunction in snorers and patients with sleep apnea.
The most likely cause for the nerve injuries is traumatic snoring vibrations and
tissue stretch, leading to swallowing dysfunction and increased risk for upper
airway obstruction during sleep.
PMID- 29966667
TI - Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With
Stable Disease.
AB - BACKGROUND: The role of the extracellular matrix (ECM) structure and remodeling
thereof in lung diseases is gaining importance. Pathology-related changes in ECM
turnover may result in deleterious changes in lung architecture, leading to
disease in the small airways. Here, degradation fragments of type I (C1M), type
IV (alpha1 chain, C4M2), and type IV (alpha3 chain, C4Ma3) collagen, all degraded
by metalloproteinases and the pro-form of collagen type V (PRO-C5) were
investigated and associated with COPD severity and outcome. METHODS: In a
prospective, observational, multicenter study including 498 patients with COPD
Gold Initiative for Chronic Obstructive Lung Disease stage 2 to 4, ECM markers
were assessed in serum at stable state, exacerbation, and at follow-up 4 weeks
after exacerbation. RESULTS: At stable state, there was a significant inverse
association between FEV1 % predicted and C1M, C4Ma3, and Pro-C5. C1M, C4M2,
C4Ma3, and Pro-C5 were associated with BMI, airflow obstruction, dyspnea, and
exercise capacity (BODE) index and the modified Medical Research Council (MMRC)
score. C1M, C4M2, C4Ma3, and Pro-C5 were significantly increased from stable
state to exacerbation and decreased at follow-up. Furthermore, the biomarkers
were significantly higher during severe exacerbation compared with moderate
exacerbation. Multivariate analysis adjusted for BMI, MMRC score, unadjusted
Charlson score, and FEV1 %predicted showed a significant influence of C1M, C4Ma3,
and C4M2 on time to exacerbation. None of the biomarkers were predictors for
mortality. CONCLUSIONS: Serologically assessed collagen remodeling appears to
play a significant role in COPD severity (airflow limitation, dyspnea) and
disease outcome (time to exacerbation and prognosis as assessed by the BODE
index).
PMID- 29966669
TI - Investigation of O-polysaccharides from bacterial strains of Pseudomonas genus as
potential receptors of bacteriophage BIM BV-45.
AB - The structure of potential bacteriophage receptors located on cell walls of Gram
negative bacteria deposited at Belarusian collection of microorganisms was
investigated. Studies by 1D and 2D 1H and 13C NMR spectroscopy enabled to
elucidate the structure of the O-specific polysaccharides (OPS) constituting
lipopolysaccharide (LPS) of some Pseudomonas species. The capacity of
bacteriophage to adsorb to LPS molecules was tested.
PMID- 29966668
TI - Preparation and characterization of MnS2/chitosan-sodium alginate and calcium
alginate nanocomposites for degradation of analgesic drug: Photocorrosion,
mechanical, antimicrobial and antioxidant properties studies.
AB - MnS2, MnS2/Chitosan-sodium Alginate (MnS2/CS-NaAlg) and MnS2/Chitosan-Calcium
Alginate (MnS2/CS-CaAlg) nanocomposites were prepared via the chemical procedure.
The characterization was performed by various instruments such as energy
dispersive X-ray spectrometer (EDX), scanning electron microscopy (SEM), X-ray
diffraction (XRD) elemental map analysis, Fourier transform infrared spectrometry
(FT-IR), Brunauer-Emmett-Teller (BET) surface area measurements, UV-Vis
absorption spectra and X-ray absorption spectroscopy. The mean crystallite sizes
of MnS2, MnS2/CS-NaAlg and MnS2/CS-CaAlg are 60.12, 71.25 and 74.54 nm,
respectively. From Kubelka-Munk equation, the energy band gaps of MnS2, MnS2/CS
NaAlg and MnS2/CS-CaAlg are estimated to be 2.83, 2.71 and 2.41 eV, respectively.
The investigation of photocatalysis properties was performed by degradation of
tramadol under UV light illumination. The optimum of experimental variables such
as pH and time on photo-degradation were found 3 and 60 min, respectively. The
results show that the efficiency photocatalysis of MnS2/CS-NaAlg and MnS2/CS
CaAlg nanocomposites under was higher than MnS2. The antibacterial and fungicidal
property of MnS2/CS-NaAlg and MnS2/CS-CaAlg nanocomposites was investigated and
demonstrates good efficiency in antimicrobial efficiency compared to MnS2. The
MnS2, MnS2/CS-NaAlg and MnS2/CS-CaAlg have been shown excellent mechanical and
antioxidant properties.
PMID- 29966670
TI - Optimization of Hericium erinaceus polysaccharide-loaded Poly (lactic-co
glycolicacid) nanoparticles by RSM and its absorption in Caco-2 cell monolayers.
AB - In present study, HEP was successfully encapsulated into the Poly (lactic
coglycolicacid) (PLGA) to constitute the HEP-PLGA. The effects of three
independent factors (the proper range of ratio of organic phase (o) to internal
water phase (w1) (X1), ratio of external water phase (w2) to the primary emulsion
(PE) (X2), and the concentration of PLGA (X3) on the extraction yield of
encapsulation efficiency (EE) from the HEP was optimized using response surface
methodology. The optimal extraction conditions for HEP-PLGA were determined as
follows: X1: 8:1, X2: 7:1 and X3: 20 mg.mL-1. Under these optimal conditions, the
mean experimental EE 90.86 +/- 0.576% was corresponded well with the predicted
value of 91.81%. In addition, to investigate the transport properties of HEP and
HEP-PLGA using a Caco-2 cell monolayer, and study the roles of the efflux
transporters (P-gp) during the transport process. These results suggested that
HEP can be absorbed more efficiently when encapsulated within the PLGA. These
findings highlight the potential to the application of HEP in the formulation of
functional foods. These results provide strategies in designing high absorbed
polysaccharides with bioactive benefits.
PMID- 29966671
TI - Comparative antibacterial effects of cellulose nanofiber, chitosan nanofiber,
chitosan/cellulose combination and chitosan alone against bacterial contamination
of Iranian banknotes.
AB - The aims of the current study were to evaluate the antibacterial effects of
cellulose nanofiber (CNF), chitosan nanofiber (ChNF), CNF/ChNF combination and
chitosan alone (Ch) against the isolated bacterial contaminations from the
surface of Iranian banknotes using biochemical, disc diffusion and molecular
analyses. The results unveiled that the CNF did not show the significant
antibacterial effect against isolated bacterial strains, whereas the combination
of CNF/ChNF (at concentration 100 MUg/disc 1:1) exhibited the synergistic effects
against Stenotrophomonas maltophilia. Also, ChNF (100 MUg/disc) and Ch (100 and
200 MUg/disc) displayed dose-dependent antibacterial effects against the
sensitive bacteria including Bacillus subtilis, Bacillus pumilus, Micrococcus sp.
Kosakonia cowanii, Brevibacterium frigoritolerans, Escherichia coli standard ATCC
25922, Staphylococcus aureus standard ATCC 25923. On the other hand, chitosan
displayed the highest inhibitory effects against Gram-positive bacteria. Our
results showed that the coating of banknotes with these compounds is a novel
strategy to reduce the bacterial contaminations and increase the durability (or
quality) of banknotes, without being toxic to the surrounding environment.
PMID- 29966672
TI - Solution plasma mediated formation of low molecular weight chitosan and its
application as a biomaterial.
AB - Low molecular weight (LMW) chitosan has been a great attention in bio-molecular
chemistry, medicine, and drug delivery system in particular. Depolymerization of
high molecular weight (HMW) chitosan to LMW chitosan was achieved by solution
plasma process (SPP) without affecting its chemical structures. Chitosan in
solution was depolymerized by discharging plasma at 800 V with 35 kHz for various
times (15-120 min). Gel permeation chromatography analysis revealed that
molecular weight of chitosan decreased from 3.0 * 105 Da to 7.8 * 103 Da in 30
min plasma treatment, and further to 4.6 * 103 Da in 90 min. Dynamic light
scattering and zeta potential studies confirmed formation of chitosan nano
aggregates. Interestingly, the LMW chitosan samples showed antimicrobial activity
against Escherichia coli, Staphylococcus aureus, and Candida albicans with
minimal inhibitory concentration of 80-1200 MUg.mL-1. They also exhibited an
excellent antioxidant activity (58-75%) and swelling ratio of 0.2-2.0 mg.mg-1.
LMW chitosan was likely to have potential for sustainable usage as carrier
molecules, biomaterials, and biomedical applications.
PMID- 29966673
TI - Starch-based dual amphiphilic graft copolymer as a new pH-sensitive maltidrug co
delivery system.
AB - Amphiphilic dual graft copolymer composed of starch (St) as main chain, poly
caprolactone (PCL) and poly (2-ethyl 2-oxazoline) (POX) as hydrophobic and
hydrophilic side chains were synthesized and characterized successfully. Firstly,
polycaprolactone with propargyl end group prepared and attached to the surface of
azido starch (St-N3) which was prepared through incomplete azidation of starch
tosylate, by click chemistry reaction. Thereafter, the polymerization of 2-ethyl
2-oxazoline initiated from the remaining tosyl groups of PCL-starch. Finally,
polymerization of POX quenched by doxorubicin (DOX) as anticancer drug as well as
terminator and curcumin (Cur) physically loaded in to the obtained copolymer.
Dual graft copolymer (PCL-St-POX) as the co-delivery system containing covalently
conjugated doxorubicin and non-covalently loaded curcumin could be promising
biocompatible system to achieve combination therapy. The SEM images showed that
resulting copolymer exhibited sphere-shaped particles ranging from 50 to 100 nm
which is completely different from ungrafted starch. The release studies also
revealed that obtained copolymer is pH-sensitive and the release rate was more
favorable at acidic pH (tumor cells) than neutral pH (normal cells) for both
drugs.
PMID- 29966674
TI - Mapping dynamic histone modification patterns during arsenic-induced malignant
transformation of human bladder cells.
AB - Arsenic is a known potent risk factor for bladder cancer. Increasing evidence
suggests that epigenetic alterations, e.g., DNA methylation and histones
posttranslational modifications (PTMs), contribute to arsenic carcinogenesis. Our
previous studies have demonstrated that exposure of human urothelial cells
(UROtsa cells) to monomethylarsonous acid (MMAIII), one of arsenic active
metabolites, changes the histone acetylation marks across the genome that are
correlated with MMAIII-induced UROtsa cell malignant transformation. In the
current study, we employed a high-resolution and high-throughput liquid
chromatography tandem mass spectrometry (LC-MS/MS) to identify and quantitatively
measure various PTM patterns during the MMAIII-induced malignant transformation.
Our data showed that MMAIII exposure caused a time-dependent increase in histone
H3 acetylation on lysine K4, K9, K14, K18, K23, and K27, but a decrease in
acetylation on lysine K5, K8, K12, and K16 of histone H4. Consistent with this
observation, H3K18ac was increased while H4K8ac was decreased in the leukocytes
collected from people exposed to high concentrations of arsenic compared to those
exposed to low concentrations. MMAIII was also able to alter histone methylation
patterns: MMAIII transformed cells experienced a loss of H3K4me1, and an increase
in H3K9me1 and H3K27me1. Collectively, our data shows that arsenic exposure
causes dynamic changes in histone acetylation and methylation patterns during
arsenic-induced cancer development. Exploring the genomic location of the altered
histone marks and the resulting aberrant expression of genes will be of
importance in deciphering the mechanism of arsenic-induced carcinogenesis.
PMID- 29966675
TI - Melatonin improves cardiac and mitochondrial function during doxorubicin-induced
cardiotoxicity: A possible role for peroxisome proliferator-activated receptor
gamma coactivator 1-alpha and sirtuin activity?
AB - Mitochondrial dysfunction is a central element in the development of doxorubicin
(DXR)-induced cardiotoxicity. In this context, melatonin is known to influence
mitochondrial homeostasis and function. This study aimed to investigate the
effects of melatonin on cardiac function, tumor growth, mitochondrial fission and
fusion, PGC1-alpha and sirtuin activity in an acute model of DXR-induced
cardiotoxicity. During the in vitro study, H9c2 rat cardiomyoblasts were pre
treated with melatonin (10 MUM, 24 h) followed by DXR exposure (3 MUM, 24 h).
Following treatment, cellular ATP levels and mitochondrial morphology were
assessed. In the in vivo study, female Sprague Dawley rats (16 weeks old), were
inoculated with a LA7 rat mammary tumor cell line and tumors were measure daily.
Animals were injected with DXR (3 * 4 mg/kg) and/or received melatonin (6 mg/kg)
for 14 days in their drinking water. Rat hearts were used to conduct isolated
heart perfusions to assess cardiac function and thereafter, heart tissue was used
for immunoblot analysis. DXR treatment increased cell death and mitochondrial
fission which were reduced with melatonin treatment. Cardiac output increased in
rats treated with DXR + melatonin compared to DXR-treated rats. Tumor volumes was
significantly reduced in DXR + melatonin-treated rats on Day 8 in comparison to
DXR-treated rats. Furthermore, DXR + melatonin treatment increased cellular ATP
levels, PGC1-alpha and SIRT1 expression which was attenuated by DXR treatment.
These results indicate that melatonin treatment confers a dual cardio-protective
and oncostatic effect by improving mitochondrial function and cardiac function
whilst simultaneously retarding tumor growth during DXR-induced cardiotoxicity.
PMID- 29966676
TI - Protective roles of NRF2 signaling pathway in cobalt chloride-induced hypoxic
cytotoxicity in human HaCaT keratinocytes.
AB - Hypoxia is a key pathological process involved in many cutaneous diseases.
Nuclear factor E2-related factor 2 (NRF2) is a central regulator of antioxidant
response element (ARE)-dependent transcription and plays a pivotal role in the
cellular adaptive response to oxidative stress. Kelch-like ECH-associated protein
1 (KEAP1) is a cullin-3-adapter protein that represses the activity of NRF2 by
mediating its ubiquitination and degradation. In the present study, we examined
the role of NRF2 signaling pathway in the cytotoxicity induced by cobalt
chloride(CoCl2), a hypoxia-mimicking agent, in human keratinocyte HaCaT cells
with stable knockdown of NRF2 (NRF2-KD) and KEAP1 (KEAP1-KD). Acute CoCl2
exposure markedly increased the levels of intracellular reactive oxygen species
(ROS), and resulted in hypoxic damage and cytotoxicity of HaCaT cells. Stable
knockdown of NRF2 dramatically reduced the expression of many antioxidant enzymes
and sensitized the cells to acute CoCl2-induced oxidative stress and
cytotoxicity. In contrast, KEAP1-KD cells observably enhanced the activity of
NRF2 and ARE-regulated genes and led to a significant resistance to CoCl2-induced
cellular damage. In addition, pretreatment of HaCaT cells with tert
butylhydroquinone, a well-known NRF2 activator, protected HaCaT cells from CoCl2
induced cellular injury in a NRF2-dependent fashion. Likewise, physical hypoxia
induced cytotoxicity could be significantly ameliorated through NRF2 signaling
pathway in HaCaT cells. Together, our results suggest that NRF2 signaling pathway
is involved in antioxidant response triggered by CoCl2-induced oxidative stress
and could protect human keratinocytes against acute CoCl2 -induced hypoxic
cytotoxicity.
PMID- 29966677
TI - Emerging functional markers for cancer stem cell-based therapies: Understanding
signaling networks for targeting metastasis.
AB - Metastasis is one of the most challenging issues in cancer patient management,
and effective therapies to specifically target disease progression are missing,
emphasizing the urgent need for developing novel anti-metastatic therapeutics.
Cancer stem cells (CSCs) gained fast attention as a minor population of highly
malignant cells within liquid and solid tumors that are responsible for tumor
onset, self-renewal, resistance to radio- and chemotherapies, and evasion of
immune surveillance accelerating recurrence and metastasis. Recent progress in
the identification of their phenotypic and molecular characteristics and
interactions with the tumor microenvironment provides great potential for the
development of CSC-based targeted therapies and radical improvement in metastasis
prevention and cancer patient prognosis. Here, we report on newly uncovered
signaling mechanisms controlling CSC's aggressiveness and treatment resistance,
and CSC-specific agents and molecular therapeutics, some of which are currently
under investigation in clinical trials, gearing towards decisive functional CSC
intrinsic or surface markers. One special research focus rests upon subverted
regulatory pathways such as insulin-like growth factor 1 receptor signaling and
its interactors in metastasis-initiating cell populations directly related to the
gain of stem cell- and EMT-associated properties, as well as key components of
the E2F transcription factor network regulating metastatic progression,
microenvironmental changes, and chemoresistance. In addition, the study provides
insight into systems biology tools to establish complex molecular relationships
behind the emergence of aggressive phenotypes from high-throughput data that rely
on network-based analysis and their use to investigate immune escape mechanisms
or predict clinical outcome-relevant CSC receptor signaling signatures. We
further propose that customized vector technologies could drastically enhance
systemic drug delivery to target sites, and summarize recent progress and
remaining challenges. This review integrates available knowledge on CSC biology,
computational modeling approaches, molecular targeting strategies, and delivery
techniques to envision future clinical therapies designed to conquer metastasis
initiating cells.
PMID- 29966678
TI - Patient-derived tumor organoids for prediction of cancer treatment response.
AB - Cancer treatment, in particular radiotherapy and chemotherapy, is often hindered
by an inherent resistance of cancer cells. Cancer stem cells in particular have
previously been shown to be more resistant than other cells within a tumor and
are thought repopulate the tumour after therapies. Therefore, it is of utmost
importance to develop tools and techniques that can be used to study mechanisms
of resistance of cancer stem cells as potential treatment targets. Organoids (and
cancer-derived organoids), are three-dimensional tissue-resembling cellular
clusters derived from tissue or tumor specific stem cells that mimic the in vivo
(tumor) characteristics, as well as (tumor) cell heterogeneity. Cancer organoids
may further enhance the in vitro and in vivo models that are currently available,
improve our understanding of cancer stem cell resistance and can be used to
develop novel cancer treatments by improved targeting of cancer stem cells. In
this review, we compare organoids with the more traditional laboratory models,
such as cell lines and xenografts, and review the literature of the current role
of cancer organoids in determining treatment responses.
PMID- 29966679
TI - Genomic analysis of multidrug-resistant Escherichia coli ST58 causing urosepsis.
AB - Sequence type 58 (ST58) phylogroup B1 Escherichia coli have been isolated from a
wide variety of mammalian and avian hosts but are not noted for their ability to
cause serious disease in humans or animals. Here we determined the genome
sequences of two multidrug-resistant E. coli ST58 strains from urine and blood of
one patient using a combination of Illumina and Single Molecule, Real-Time (SMRT)
sequencing. Both ST58 strains were clonal and were characterised as serotype
O8:H25, phylogroup B1 and carried a complex resistance locus/loci (CRL) that
featured an atypical class 1 integron with a dfrA5 (trimethoprim resistance) gene
cassette followed by only 24 bp of the 3'-CS. CRL that carry this particular
integron have been described previously in E. coli from cattle, pigs and humans
in Australia. The integron abuts a copy of Tn6029, an IS26-flanked composite
transposon encoding blaTEM, sul2 and strAB genes that confer resistance to
ampicillin, sulfathiazole and streptomycin, respectively. The CRL resides within
a novel Tn2610-like hybrid Tn1721/Tn21 transposon on an IncF, ColV plasmid
(pSDJ2009-52F) of 138 553 bp that encodes virulence associated genes implicated
in life-threatening extraintestinal pathogenic E. coli (ExPEC) infections.
Notably, pSDJ2009-52F shares high sequence identity with pSF-088-1, a plasmid
reported in an E. coli ST95 strain from a patient with blood sepsis from a
hospital in San Francisco. These data suggest that extraintestinal infections
caused by E. coli carrying ColV-like plasmids, irrespective of their phylogroup
or ST, may pose a potential threat to human health, particularly to the elderly
and immunocompromised.
PMID- 29966680
TI - Ghrelin stimulates intestinal adaptation following massive small bowel resection
in parenterally fed rats.
AB - BACKGROUND: Since short bowel syndrome (SBS) patients face life-threatening
conditions, the development of therapeutic strategies to induce intestinal
adaptation has been investigated. Ghrelin, a ligand of growth hormone (GH)
secretagogue-receptor that stimulates the release of GH and insulin like growth
factor-1 (IGF-1), has several pleiotropic effects. We investigated whether
ghrelin induces intestinal adaptation in parenterally fed rats with SBS. METHODS:
Sprague-Dawley rats underwent venous catheterization and were divided into 3
groups: those receiving 90% small bowel resection while leaving the proximal
jejunum and distal ileum (90% SBR) with TPN (SBS/TPN group), those receiving 90%
SBR with TPN + ghrelin (SBS/TPN/ghrelin group), and those receiving sham
operation and fed chow (sham group). Ghrelin was administered intravenously at 10
MUg/kg/day. On Day 13, the rats were euthanized and the small intestine
harvested, and the histology and crypt cell proliferation rates (CCPR),
apoptosis, and nutrient transporter protein levels were analyzed and the plasma
hormones were measured. RESULTS: The villus height and crypt depth of the ileum
in the SBS/TPN/ghrelin group were significantly higher than in the SBS/TPN group.
The CCPR of the jejunum and the ileum significantly increased by the
administration of ghrelin; however, the apoptosis rates did not significantly
differ between the SBS/TPN and SBS/TPN/ghrelin groups. Significant differences
did not exist in the plasma IGF-1 and nutrient transporter protein levels among
three groups. CONCLUSIONS: The intravenous administration of ghrelin stimulated
the morphological intestinal adaptation of the ileum to a greater degree than the
jejunum due to the direct effect of ghrelin.
PMID- 29966681
TI - ZNF154 is a promising diagnosis biomarker and predicts biochemical recurrence in
prostate cancer.
AB - OBJECTIVE: To screen the methylated genes for early diagnosis and biochemical
recurrence (BCR) prediction in prostate cancer (PCa) patients. METHODS:
Differentially methylated CpG sites (DMCs) of PCa were screened out from The
Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database.
Combined with TCGA RNA sequencing data and clinical information, the DMCs
associated genes with different expression and related to BCR were selected as
candidate genes. Then, the expression level of the best candidate gene ZNF154 was
validated by quantitative real-time polymerase chain reaction (qRT-PCR). Finally,
the prognosis potential of the hypermethylation gene ZNF154 was assessed by
Kaplan-Meier, univariate and multivariate cox regression analysis. RESULTS: A
total of 87 candidate genes were screened out. Compared to benign prostate (BP)
tissues, ZNF154 has three hypermethylation sites (cg03234186, cg12506930,
cg26465391) in the promoter region in PCa tissues. qRT-PCR results showed that
ZNF154 expression level was reduced in PCa tissues than in BP tissues (P =
0.004). Besides, the ZNF154 methylation level was negatively correlated with mRNA
expression (r = -0.766, P < 0.001), and was highly cancer-specific in PCa (area
under the curves (AUCs) = 90.030%). In addition, Kaplan-Meier analysis showed
ZNF154 methylation level was associated with BCR (P = 0.005), and ZNF154 could be
an independent factor for BCR prediction in PCa by using univariate and
multivariate cox regression analysis (P = 0.035, HR = 8.218). CONCLUSIONS: 87 PCa
specific genes were obtained. Further analysis gave the evidence that ZNF154 can
be used as a specific maker for PCa diagnosis. Hypermethylation level of ZNF154
lead to gene expression inhibition and function loss, which contribute to the
development and poor outcomes in PCa. In addition, the mean methylation level of
ZNF154 can be used as an independent risk factor to predict BCR.
PMID- 29966682
TI - Caspase-independence and characterization of bisnaphthalimidopropyl spermidine
induced cytotoxicity in HL60 cells.
AB - Bisnaphthalimides are DNA intercalators of potential use as chemotherapeutics but
for which the range of mechanism of action is only gradually being elucidated.
Using human promyelocytic HL-60 cells, we extend characterization of the
cytotoxicity of bisnaphthalimidopropylspermidine (BNIPSpd) and examine the
relationship with caspase-activity. Within 4 h exposure, BNIPSpd (1-10 MUM)
induced significant DNA strand breakage. Evidence of apoptosis was progressive
through the experimental period. Within 6 h, BNIPSpd increased the proportion of
cells exhibiting plasma membrane phosphatidylserine exposure. Within 12 h, active
caspase expression increased and was sustained with 5 and 10 MUM BNIPSpd. Flow
cytometric analysis revealed caspase activity in cells with and without damaged
membranes. By 24 h, 5 and 10 MUM BNIPSpd increased hypodiploid DNA content and
internucleosomal DNA fragmentation (DNA ladders) typical of the later stages of
apoptosis. 1 MUM BNIPSpd exposure also increased hypodiploid DNA content by 48 h.
Polyamine levels decreased by 24 h BNIPSpd exposure. The pan-caspase inhibitor, z
VAD-fmk, significantly decreased DNA degradation (hypodiploid DNA and DNA
ladders) and cytotoxicity. Despite this, cell growth and viability remained
significantly impaired. We propose that BNIPSpd cytotoxicity arises through DNA
damage and not polyamine depletion and that cytotoxicity is dominated by but not
dependent upon caspase driven apoptosis.
PMID- 29966683
TI - 'Kids save lives' in Hungary-Implementation, opportunities, programmes, opinions,
barriers.
PMID- 29966684
TI - Bioresponsive drug delivery systems in intestinal inflammation: State-of-the-art
and future perspectives.
AB - Oral colon-specific delivery systems emerged as the main therapeutic cargos by
making a significant impact in the field of modern medicine for local drug
delivery in intestinal inflammation. The site-specific delivery of therapeutics
(aminosalicylates, glucocorticoids, biologics) to the ulcerative mucus tissue can
provide prominent advantages in mucosal healing (MH). Attaining gut mucosal
healing and anti-fibrosis are main treatment outcomes in inflammatory bowel
disease (IBD). The pharmaceutical strategies that are commonly used to achieve a
colon-specific drug delivery system include time, pH-dependent polymer coating,
prodrug, colonic microbiota-activated delivery systems and a combination of these
approaches. Amongst the different approaches reported, the use of biodegradable
polysaccharide coated systems holds great promise in delivering drugs to the
ulcerative regions. The present review focuses on major physiological gastro
intestinal tract challenges involved in altering the pharmacokinetics of delivery
systems, pathophysiology of MH and fibrosis, reported drug-polysaccharide cargos
and focusing on conventional to advanced disease responsive delivery strategies,
highlighting their limitations and future perspectives in intestinal inflammation
therapy.
PMID- 29966685
TI - Regulatory challenges of nanomedicines and their follow-on versions: A generic or
similar approach?
AB - Nanomedicines and follow-on versions (also called nanosimilars in the EU) have
been on the market partially for decades although without recognition of their
nano properties in the beginning; a substantial number is in clinical
development. Nanomedicines are typically synthetic and belong to the non
biological complex drugs. They show a high variability in form, structure, and
size. Additionally large molecule biologics show nano-characteristics meaning
nano-dimension in size (1-100 nm) or specific properties related to these
dimensions. The high complexity of nanomedicines with their heterogeneous
structures do not allow a full physicochemical quality characterization,
challenging the regulatory evaluation especially for follow-on versions upon
comparison with the reference product. The generic paradigm with the sameness
approach for quality and bioequivalence in blood plasma is not appropriate for
nanomedicines where a similar approach is needed. After experiencing non
equivalence of authorized parenteral colloidal iron follow-on versions, EMA and
FDA issued reflection papers and draft guidances for industry to present their
current thinking on the evaluation of such complex products. A stepwise approach
to evaluate the extent of similarity, from quality, including critical quality
attributes (CQA) and assessment of nano properties, to a non-clinical
biodistribution assay, required in the the EU but not in the US, and to clinical
evaluation makes sense. The cumulated totality of evidence for the authorization
of nanomedicine follow-on versions goes case-by-case. Interchangeability, or
substitutability, is a challenge. However, a defined or even harmonized approval
pathway for these follow-versions is still missing and causes potential
differences in approval. To progress, a science-based discussion platform among
stakeholders and experts in the field is necessary. An agenda has been agreed
[5], namely CQA assessment, publication of scientific and clinical findings,
consensus on nomenclature and labelling, and regulatory actions on substandard
complex drug products. Consensus created in a public private approach will
support progress towards a defined and harmonized regulatory pathway for
nanomedicines and their follow-on versions. This will provide drug innovation but
also larger access to follow-on versions of nanomedicines, both a benefit for the
patient.
PMID- 29966686
TI - Next-generation museum genomics: Phylogenetic relationships among palpimanoid
spiders using sequence capture techniques (Araneae: Palpimanoidea).
AB - Historical museum specimens are invaluable for morphological and taxonomic
research, but typically the DNA is degraded making traditional sequencing
techniques difficult to impossible for many specimens. Recent advances in Next
Generation Sequencing, specifically target capture, makes use of short fragment
sizes typical of degraded DNA, opening up the possibilities for gathering genomic
data from museum specimens. This study uses museum specimens and recent target
capture sequencing techniques to sequence both Ultra-Conserved Elements (UCE) and
exonic regions for lineages that span the modern spiders, Araneomorphae, with a
focus on Palpimanoidea. While many previous studies have used target capture
techniques on dried museum specimens (for example, skins, pinned insects), this
study includes specimens that were collected over the last two decades and stored
in 70% ethanol at room temperature. Our findings support the utility of target
capture methods for examining deep relationships within Araneomorphae: sequences
from both UCE and exonic loci were important for resolving relationships; a
monophyletic Palpimanoidea was recovered in many analyses and there was strong
support for family and generic-level palpimanoid relationships. Ancestral
character state reconstructions reveal that the highly modified carapace observed
in mecysmaucheniids and archaeids has evolved independently.
PMID- 29966687
TI - Fish pathogen bacteria: Adhesion, parameters influencing virulence and
interaction with host cells.
AB - Wild fisheries are declining due to over-fishing, climate change, pollution and
marine habitat destructions among other factors, and, concomitantly, aquaculture
is increasing significantly around the world. Fish infections caused by
pathogenic bacteria are quite common in aquaculture, although their seriousness
depends on the season. Drug-supplemented feeds are often used to keep farmed fish
free from the diseases caused by such bacteria. However, given that bacteria can
survive well in aquatic environments independently of their hosts, bacterial
diseases have become major impediments to aquaculture development. On the other
hand, the indiscriminate uses of antimicrobial agents has led to resistant
strains and the need to switch to other antibiotics, although it seems that an
integrated approach that considers not only the pathogen but also the host and
the environment will be the most effective method in the long-term to improve
aquatic animal health. This review covers the mechanisms of bacterial
pathogenicity and details the foundations underlying the interactions occurring
between pathogenic bacteria and the fish host in the aquatic environment, as well
as the factors that influence virulence. Understanding and linking the different
phenomena that occur from adhesion to colonization of the host will offer novel
and useful means to help design suitable therapeutic strategies for disease
prevention and treatment.
PMID- 29966688
TI - Differentially expressed genes in hemocytes of Litopenaeus vannamei challenged
with Vibrio parahaemolyticus AHPND (VPAHPND) and VPAHPND toxin.
AB - While toxin-harboring Vibrio parahaemolyticus has been previously established as
the causative agent of early mortality syndrome (EMS) or acute hepatopancreatic
necrosis disease (AHPND) in shrimp, information on the mechanistic processes that
happen in the host during infection is still lacking. Here, we examined the
expression responses of the shrimp hemocyte transcriptome to V. parahaemolyticus
AHPND (VPAHPND) by RNA sequencing (RNA-seq). Using libraries (SRA accession
number SRP137285) prepared from shrimp hemocytes under experimental conditions, a
reference library was de novo assembled for gene expression analysis of VPAHPND
challenged samples at 0, 3/6, and 48 h post infection (hpi). Using the library
from 0-hpi as the control, 359 transcripts were found to be differentially
expressed in the 3/6-hpi library, while 429 were differentially expressed in the
48-hpi library. The expression patterns reported in the RNA-seq of 9
representative genes such as anti-lipopolysaccharide factor (LvALF), crustin p
(CRU), serpin 3 (SER), C-type lectin 3 (CTL), clottable protein 2 (CLO), mitogen
activated protein kinase kinase 4 (MKK4), P38 mitogen-activated protein kinase
(P38), protein kinase A regulatory subunit 1 (PKA) and DNAJ homolog subfamily C
member 1-like (DNJ) were validated by qRT-PCR. The expression of these genes was
also analyzed in shrimp that were injected with the partially purified VPAHPND
toxin. A VPAHPND toxin-responsive gene, LvALF was identified, and its function
was characterized by RNA interference. LvALF knockdown resulted in significantly
rapid increase of shrimp mortality caused by toxin injection. Protein-protein
interaction analysis by molecular docking suggested that LvALF possibly
neutralizes VPAHPND toxin through its LPS-binding domain. The data generated in
this study provide preliminary insights into the differences in the immune
response of shrimp to the bacterial and toxic aspect of VPAHPND as a disease.
PMID- 29966689
TI - Prolonged engraftment of transplanted hepatocytes in the liver by transient pro
survival factor supplementation using ex vivo mRNA transfection.
AB - Cell transplantation therapy needs engraftment efficiency improvement of
transplanted cells to the host tissues. Ex vivo transfection of a pro-survival
gene to transplanted cells is a possible solution; however prolonged expression
and/or genomic integration of the gene can be cancer promoting. To supply pro
survival protein only when it is needed, we used mRNA transfection, which
exhibits transient protein expression profiles without the risk of genomic
integration. Ex vivo transfection of mRNA encoding Bcl-2, a pro-survival factor,
led to enhanced hepatocyte engraftment in both of normal and diseased mouse
liver, effectively supporting liver function in a model of chronic hepatitis. The
transplanted hepatocytes maintained their viability and function in the liver for
at least one month, though Bcl-2 expression from mRNA was sustained for just a
few days. Mechanism analyses suggest that Bcl-2 inhibits Kupffer cell-mediated
hepatocyte clearance, which occurs within 2 days after transplantation. Within 2
days, hepatocytes migrated to the liver parenchyma, presumably a suitable place
for the hepatocytes to survive without Bcl-2 expression. Thus, the duration of
Bcl-2 expression from mRNA was sufficient to achieve prolonged engraftment. Ex
vivo mRNA transfection allows supply of pro-survival factors to transplanted
cells with minimal safety concerns accompanying prolonged expression, providing
an effective platform to improve engraftment efficiency in cell transplantation
therapy.
PMID- 29966690
TI - Two sides of a coin: GG genotype of C7 provides protection against fibrosis
severity while showing a higher risk for hepatocellular carcinoma in patients
with hepatitis C.
AB - The complement system (CS) is a key element of immunity against pathogens but
also seems to influence other events, such as tumorigenesis and tissue repair.
Complement component 7 (C7) is a key component of the lytic pathway of CS,
leading to the formation of the membrane attack complex (MAC). This study aimed
to investigate the existence of the association of a polymorphism in the C7 gene,
rs1063499, with hepatic fibrosis and the occurrence of hepatocellular carcinoma
(HCC) in patients with hepatitis C. We analyzed 456 samples from patients with
chronic hepatitis C. Real-time PCR was used for allelic discrimination. Patients
were classified by their METAVIR score as F1 (n = 100), F2 (n = 83), F3 (n = 101)
or F4 (n = 66); 106 patients were diagnosed with HCC. Patients carrying the G/G
genotype of C7 had a lower chance of developing severe fibrosis in the recessive
model (p = 0.042; OR: 0.65 95% CI 0.41-1.02). However, the G/G genotype frequency
was higher in patients with HCC (P = 0.01; OR: 2.07 95% CI 1.20-3.53) and in
those with larger tumors (p = 0.04). The G/G C7 genotype seems to be a protective
factor against advanced fibrosis; however, it was associated with a higher risk
of HCC and the occurrence of larger hepatic nodules, suggesting the involvement
of C7 in the physiopathogenesis of HCC and fibrosis in patients with hepatitis C
virus (HCV).
PMID- 29966691
TI - Interleukin-25 reduces Th17 cells and inflammatory responses in human peripheral
blood mononuclear cells.
AB - BACKGROUND: The absence of interleukin-25 (IL-25) favors the induction of Th1 and
Th17 immune responses in mice. Th1 immune responses have been associated with the
pathology of atherosclerosis, a lipid and inflammation driven disease of the
arterial wall. PURPOSE OF RESEARCH: To evaluate the effect of IL-25 on human
peripheral blood mononuclear cells (hPBMCs) in the presence and absence of
oxidized low density lipoprotein (oxLDL), a key player in atherosclerosis
development. PRINCIPAL RESULTS: Human PBMCs were incubated with recombinant human
IL-25 (rhIL-25) in the presence and absence of oxLDL and analyzed with flow
cytometry while cytokine secretion was measured in cell culture supernatants. The
IL-25 receptor, IL-17RB, was mostly expressed on T cells. Incubation of hPBMCs
with IL-25 reduced the frequency of Th17 cells. Furthermore, IL-25 inhibited the
release of the Th17-inducing cytokine IL-6 from dendritic cells isolated from
hPBMCs indicating that the IL-25 mediated Th17 suppression may be indirect.
Moreover, IL-25 reduced the secretion of the proinflammatory cytokine IFNgamma
from hPBMCs. OxLDL decreased IFNgamma release from hPBMCs regardless of the
presence or absence of IL-25. CONCLUSIONS: IL-25 reduces Th1 and Th17 immune
responses in hPBMCs raising the interesting possibility that IL-25 could have a
protective role in human atherosclerosis.
PMID- 29966692
TI - The complete mitochondrial genome of Eterusia aedea (Lepidoptera, Zygaenidae) and
comparison with other zygaenid moths.
AB - Zygaenidae comprises >1036 species, including many folivorous pests in
agriculture. In the present study, the complete mitochondrial genome (mitogenome)
of a major pest of tea trees, Eterusia aedea was determined. The 15,196-bp
circular genome contained the common set of 37 mitochondrial genes (including 13
protein-coding genes, two rRNA genes, and 22 tRNA genes) and exhibited the
similar genomic features to reported Zygaenidae mitogenome. Comparative analyses
of Zygaenidae mitogenomes showed a typical evolutionary trend of lepidopteran
mitogenomes. In addition, we also investigated the gene order of lepidopteran
mitogenomes and proposed that the novel gene order trnA-trnR-trnN-trnE-trnS-trnF
from Zygaenidae and Gelechiidae and most other gene rearrangements of this tRNA
cluster evolved independently. Finally, the mitogenomic phylogeny of Lepidoptera
was reconstructed based on multiple mitochondrial datasets. And all the
phylogenetic results revealed the sister relationships of Cossoidea and
Zygaenoidea with both BI and ML methods, which is the first stable mitogenomic
evidence for this clade.
PMID- 29966693
TI - Optimized super-selective Arterial Spin Labeling for quantitative flow territory
mapping.
AB - Flow territory mapping using Arterial Spin Labeling (ASL) methods allows for
deeper insights into the physiology of the brain. However, in most approaches
assumptions of the labeling efficiency are used for calculation of brain
perfusion which might result in inaccuracies. This becomes more important in
super-selective ASL as the labeling focus could be positioned not exactly at the
artery of interest. Therefore, measuring the labeling efficiency of the current
scan seems important to obtain reliable results and to correct for potential
errors. In this study, an optimized super-selective ASL tagging scheme is
presented and the labeling efficiency is measured using quantitative phase
contrast angiography of the tagged artery and considering the volume of the
supplied flow territory. The aim then is to evaluate the labeling efficiency of
super-selective ASL and considering these values when shifting the labeling spot
away from the artery of interest. The measured efficiency is compared to
simulations performed for the optimized super-selective ASL approach. Considering
the values of labeling efficiency after shifting the labeling focus, the values
of cerebral blood flow still show accurate results despite the expected lower SNR
up to an offset of 3 mm. Following this, to obtain accurate results for
quantifying super-selective ASL perfusion images, measuring the labeling
efficiency seems necessary to prevent false results.
PMID- 29966694
TI - From Pull to Pressure: Effects of Tourniquet Buckles and Straps.
AB - BACKGROUND: Limb tourniquet pressures > 100 mmHg before tightening system use
eases achieving arterial occlusion, minimizes tightening system problems, and
probably minimizes discomfort. This study examined effects of buckle and strap
features on converting pulling force to strap pressure. STUDY DESIGN: Twenty-two
buckle and strap combinations were evaluated using a thigh-diameter, ballistic
gel cylinder and 3 thighs. Weights of 14.11, 27.60, and 41.11 kg provided pulling
force. The contribution of buckle movement was evaluated: all buckles on gel and
12 on thighs allowed limited vertical movement, 12 on gel and 4 on thighs held
static. RESULTS: Force conversion patterns per combination were similar on gel
and thighs, including greatest force conversion with some buckle movement
allowed. Smooth, round redirect buckles without engagement of a strap-securing
mechanism had the best conversions of pulling force to tourniquet pressure; 2
achieved arterially occlusive pressures, neither commercially available. Among
hook-and-loop secured tourniquets and threaded for self-securing tourniquets, the
Generation 7 Combat Application Tourniquet (C-A-T7) and the Tactical Ratcheting
Medical Tourniquet (Tac RMT) had the best conversions of pull to pressure (thigh
applications/each weight, mean +/- SD: C-A-T7 91 +/- 11, 164 +/- 30, 228 +/- 34
mmHg; Tac RMT 82 +/- 13, 150 +/- 16, 222 +/- 17 mmHg). Other Ratcheting Medical
Tourniquets with the same buckle but different strap fabrics performed less well.
Even lower pressures occurred with the Tactical Mechanical Tourniquet, the
Special Operations Forces Tactical Tourniquet, the Parabelt, and the SAM XT
Extremity Tourniquet (165 +/- 11, 178 +/- 13, 131 +/- 14, and 106 +/- 14 mmHg,
all at 41.11 kg, respectively). CONCLUSIONS: Buckle design and strap fabric
affect the conversion of pulling force to tourniquet strap pressure. Low
friction, smooth, round redirects allow the best conversion.
PMID- 29966695
TI - Fractal dimension of EEG signals and heart dynamics in discrete emotional states.
AB - In this study, we explored the fractal dimension (FD; a measure of signal
complexity) of 28 EEG channels with positive and negative emotional states. The
EEG of participants and their ECG were registered while watching short video
clips that induced fear, disgust, humour, or neutral emotions. In order to better
understand the nature of these emotions, the Higuchi FD of EEG segments and the
heart rate variability (HRV) of the ECG associated with each emotion were
obtained. Our results exhibited similar patterns of results with both measures.
Humour elicited the highest FD scores in most EEG channels and the highest HRV,
while fear, among all emotions, produced the lowest scores in both measures.
These results may contribute to the understanding of the relationship between
cortical and heart dynamics and their role on emotion perception.
PMID- 29966696
TI - Mutation goals in the vitamin D receptor predicted by computational methods.
AB - The mechanism through which nuclear receptors respond differentially to
structurally distinct agonists is a poorly understood process. We present a
computational method that identifies nuclear receptor amino acids that are likely
involved in biological responses triggered by ligand binding. The method involves
tracing how structural changes spread from the ligand binding pocket to the sites
on the receptor surface, which makes it a good tool for studying allosteric
effects. We employ the method to the vitamin D receptor and verify that the
identified amino acids are biologically relevant using a broad range of
experimental data and a genome browser. We infer that surface vitamin D receptor
residues K141, R252, I260, T280, T287 and L417 are likely involved in cell
differentiation and antiproliferation, whereas P122, D149, K321, E353 and Q385
are linked to carcinogenesis.
PMID- 29966697
TI - Pyridine nucleotides regulate the superoxide anion flash upon permeabilization of
mitochondrial membranes: An MCLA-based study.
AB - The permeabilization of mitochondrial membranes via permeability transition pore
opening or by the pore-forming peptide alamethicin causes a flash of superoxide
anion (SA) and hydrogen peroxide production and the inhibition of matrix
aconitase. It was shown using the SA probe 3,7-dihydro-2-methyl-6-(4
methoxyphenyl)imidazol[1,2-a]pyrazine-3-one (MCLA) that the substrates of NAD
dependent dehydrogenases, inhibitors of the respiratory chain, and NAD(P)H at
millimolar concentrations suppressed or delayed SA flashes. In the presence of
added NADH and NADPH, SA flashes were observed only after considerable oxidation
of pyridine nucleotides. The production of SA was maximal at NADPH and NADH redox
potentials from -315 to -295 mV and from -325 to -270 mV, respectively, depending
on NAD(P)H concentration. SA generation supported by NADPH was severalfold
greater than that supported by NADH. In intact mitochondria, NADPH- and NADH
dependent SA generation was negligible. Respiratory substrates at physiological
or lower concentrations were incapable of suppressing the NADPH-supported SA
flash. These data indicate that, in conditions close to pathophysiological,
matrix NADPH oxidoreductase(s), presumably, an adrenodoxin reductase in complex
with adrenodoxin, can essentially contribute to SA flashes associated with
transient or irreversible permeability transition pore opening or membrane
permeabilization by another mechanism.
PMID- 29966698
TI - Cerebroprotection by salvianolic acid B after experimental subarachnoid
hemorrhage occurs via Nrf2- and SIRT1-dependent pathways.
AB - Salvianolic acid B (SalB), a natural polyphenolic compound extracted from the
herb of Salvia miltiorrhiza, possesses antioxidant and neuroprotective properties
and has been shown to be beneficial for diseases that affect vasculature and
cognitive function. Here we investigated the protective effects of SalB against
subarachnoid hemorrhage (SAH)-induced oxidative damage, and the involvement of
underlying molecular mechanisms. In a rat model of SAH, SalB inhibited SAH
induced oxidative damage. The reduction in oxidative damage was associated with
suppressed reactive oxygen species generation; decreased lipid peroxidation; and
increased glutathione peroxidase, glutathione, and superoxide dismutase
activities. Concomitant with the suppressed oxidative stress, SalB significantly
reduced neurologic impairment, brain edema, and neural cell apoptosis after SAH.
Moreover, SalB dramatically induced nuclear factor-erythroid 2-related factor 2
(Nrf2) nuclear translocation and increased expression of heme oxygenase-1 and
NADPH: quinine oxidoreductase-1. In a mouse model of SAH, Nrf2 knockout
significantly reversed the antioxidant effects of SalB against SAH. Additionally,
SalB activated sirtuin 1 (SIRT1) expression, whereas SIRT1-specific inhibitor
sirtinol pretreatment significantly suppressed SalB-induced SIRT1 activation and
Nrf2 expression. Sirtinol pretreatment also reversed the antioxidant and
neuroprotective effects of SalB. In primary cultured cortical neurons, SalB
suppressed oxidative damage, alleviated neuronal degeneration, and improved cell
viability. These beneficial effects were associated with activation of the SIRT1
and Nrf2 signaling pathway and were reversed by sirtinol treatment. Taken
together, these in vivo and in vitro findings suggest that SalB provides
protection against SAH-triggered oxidative damage by upregulating the Nrf2
antioxidant signaling pathway, which may be modulated by SIRT1 activation.
PMID- 29966699
TI - The prostanoid pathway contains potential prognostic markers for glioblastoma.
AB - Prostanoids derived from the activity of cyclooxygenases and their respective
synthases contribute to both active inflammation and immune response in the tumor
microenvironment. Their synthesis, deactivation and role in glioma biology have
not yet been fully explored and require further study. Using quantitative real
time PCR, gas chromatography/ electron impact mass spectrometry and liquid
chromatography/ electrospray ionization tandem mass spectrometry, we have further
characterized the prostanoid pathway in grade IV glioblastoma (GBM). We observed
significant correlations between high mRNA expression levels and poor patient
survival for microsomal PGE synthase 1 (mPGES1) and prostaglandin reductase 1
(PTGR1). Conversely, high mRNA expression levels for 15-hydroxyprostaglandin
dehydrogenase (15-HPGD) were correlated with better patient survival. GBMs had a
higher quantity of the prostanoid precursor, arachidonic acid, versus grade
II/III tumors and in GBMs a significant positive correlation was found between
arachidonic acid and PGE2 content. GBMs also had higher concentrations of TXB2,
PGD2, PGE2 and PGF2alpha versus grade II/III tumors. A significant decrease in
survival was detected for high versus low PGE2, PGE2 + PGE2 deactivation products
(PGEMs) and PGF2alpha in GBM patients. Our data show the potential importance of
prostanoid metabolism in the progression towards GBM and provide evidence that
higher PGE2 and PGF2alpha concentrations in the tumor are correlated with poorer
patient survival. Our findings highlight the potential importance of the enzymes
15-HPGD and PTGR1 as prognostic biomarkers which could be used to predict
survival outcome of patients with GBM.
PMID- 29966700
TI - The reproductive system of Limnopilos naiyanetri indicates a thoracotreme
affiliation of Hymenosomatidae (Decapoda, Eubrachyura).
AB - The eubrachyuran Hymenosomatoidea is widely distributed in tropical and
subtropical regions ranging from marine to freshwater habitats. Even though the
biology of this taxon has been studied to some extent, its phylogenetic
relationships are not resolved. Based on different morphological characters, some
authors suggested a close affinity of hymenosomatid crabs to heterotremes.
However, many of these characters are ambiguous, and the few molecular studies
did not provide convincing solutions either. To address this issue, we studied
the reproductive system of the hymenosomatid freshwater species Limnopilos
naiyanetri Chuang and Ng, 1991 using histology and scanning electron microscopy.
The females show the characteristic organization of the paired eubrachyuran
reproductive system. Additionally, a bursa (an accessory sperm storing cuticle
cavity) is present. The male copulatory system is characterized by paired long
first and short second gonopods, and a pair of sternal gonopores equipped with a
penis. Both, the female and male reproductive organs reveal a number of
similarities to thoracotreme crabs. The seminal receptacle is lined by a very
thin cuticle and by a mono-layered glandular epithelium. The male gonopods and
the sternal genital opening also resemble the thoracotreme condition. Thus, our
results indicate that Hymenosomatidae are most likely part of the Thoracotremata.
PMID- 29966701
TI - Draft genome sequences of two ciprofloxacin-resistant Salmonella enterica subsp.
enterica serotype Kentucky ST198 isolated from retail chicken carcasses in Egypt.
AB - OBJECTIVES: Salmonella enterica serotypes, particularly antimicrobial-resistant
strains, pose a major threat to public health worldwide. This study describes the
draft genome sequences of two ciprofloxacin-resistant Salmonella enterica subsp.
enterica serotype Kentucky isolates (H5 and H18) recovered from chicken carcass
rinsates in Mansoura, Egypt. METHODS: Antimicrobial susceptibility phenotypes
were determined for the two Salmonella Kentucky isolates by broth microdilution
using a SensititreTM system. Genomic DNA from both isolates was sequenced using
an Illumina MiSeq system. Antimicrobial resistance genes were identified using
ARG-ANNOT, and multilocus sequence typing (MLST) was performed using MLST 1.8.
RESULTS: The draft genome for Salmonella Kentucky H5 contained 4.84Mbp in 54
contigs, and that for Salmonella Kentucky isolate H18 contained 4.94Mbp in 64
contigs. Sequence analysis using ARG-ANNOT identified the presence of the
resistance genes blaTEM-57, aadA1, aadA2, cmlA1, sul3 and tetA in both isolates,
whereas dfrA, sul2, floR, and aph(3)-Ia were found in isolate H18 only. The amino
acid substitutions Ser83Phe and Asp87Gly in GyrA and Thr57Ser and Ser80Ile in
ParC were detected in both isolates. Both isolates belonged to ST198. CONCLUSION:
The draft genome sequences allowed identification of a ciprofloxacin-resistant
Salmonella Kentucky ST198 epidemic clone with multidrug resistance in poultry
products produced for human consumption in Egypt. These data indicate that
poultry continues to be a reservoir for this persistent clone.
PMID- 29966702
TI - OqxAB and variants of QepA in extended-spectrum beta-lactamase-producing
Enterobacteriaceae in hospital wastewater in Mali.
PMID- 29966703
TI - Mechanisms of allergen-specific immunotherapy: Diverse mechanisms of immune
tolerance to allergens.
AB - OBJECTIVE: The aim of this review is to provide an overview of the current
knowledge on the mechanisms of allergen immunotherapy based on the recent
publications and clinical trials. DATA SOURCES: PubMed literature review. STUDY
SELECTIONS: In this review, we focus on diverse mechanisms of AIT and provide an
insight into alternative routes of administration. Additionally, we review and
discuss the most recent studies investigating potential biomarkers and highlight
their role in clinical settings. RESULTS: Successful allergen-specific
immunotherapy (AIT) induces the reinstatement of tolerance toward allergens and
represents a disease-modifying treatment. In the last decades, substantial
progress in understanding the mechanisms of AIT has been achieved. Establishment
of long-term clinical tolerance to allergens engages a complex network of
interactions, modulating the functions of basophils, mast cells, allergen
specific regulatory T and B cells, and production of specific antibodies. The
reduction of symptoms and clinical improvement is achieved by skewing the immune
response away from allergic inflammation. CONCLUSION: Although the complex nature
of AIT mechanisms is becoming more clear, the need to discover reliable
biomarkers to define patients likely to respond to the treatment is emerging.
PMID- 29966704
TI - Specific-IgE to galactose-alpha-1,3-galactose (alpha-gal) has limited utility in
diagnosing meat allergy in a tick-endemic population.
PMID- 29966705
TI - Successful desensitization in a pediatric patient with acetazolamide allergy.
PMID- 29966706
TI - Sclerosing Cholangitis-Like Changes on Magnetic Resonance Cholangiography in
Patients With Drug Induced Liver Injury.
PMID- 29966707
TI - High-resolution Anorectal Manometry Measures Are More Accurate Than Conventional
Measures in Detecting Anal Hypocontractility in Women With Fecal Incontinence.
AB - BACKGROUND & AIMS: Anorectal manometry is a common test of anal tone and
contractility. However, existing measures are often criticized for their poor
ability to detect functional differences between individuals with presumably
normal sphincter function and individuals with fecal incontinence. We
investigated whether new measures, derived from high-resolution anal manometry
(HR-ARM), more accurately identify incontinent women with abnormal sphincter
function than measures from conventional anal manometry (C-ARM). METHODS: We
performed a prospective HR-ARM study of 85 healthy female volunteers (median age
41 years; range 18-68 years) and 403 women with fecal incontinence (median age
55; range 18-91 years) from June 2013 through December 2015. We compared the
diagnostic accuracy of conventional measurements of contractility (C-ARM squeeze
increment) and tone (C-ARM resting pressure) (the reference standard), with HR
ARM measures (HR-ARM squeeze increment, HR-ARM contractile integral, HR-ARM
resting average, HR-ARM rest integral). We also investigated associations between
symptom severity and structural sphincter integrity. RESULTS: We identified anal
hypocontractility in 129 women with fecal incontinence using the C-ARM squeeze
increment (32% sensitivity; likelihood ratio, 6.4), in 189 women using the HR-ARM
squeeze increment (47% sensitivity; likelihood ratio, 9.4), and in 220 women
using the HR-ARM contractile integral (55% sensitivity; likelihood ratio, 11.0).
In contrast, HR-ARM measures of anal tone did not particularly outperform
conventional measures (31% sensitivity for HR-ARM resting average vs 28% for C
ARM resting pressure). Ninety-eight of the 206 patients with fecal incontinence
who were classified as having normal anal function, based on C-ARM measures, were
reclassified as having abnormal function based on HR-ARM measures. CONCLUSION: In
a prospective study of healthy women and women with fecal incontinence, we
demonstrated that the newly developed HR-ARM contractile integral increased the
sensitivity of detection of anal hypocontractility, from 32% to 55%, compared
with conventional measurements of squeeze.
PMID- 29966708
TI - Evaluating the Combination of Microsatellite Instability and Mutation in BRAF as
Prognostic Factors for Patients With Colorectal Cancer.
PMID- 29966709
TI - Features of Postcolonoscopy Colorectal Cancer and Survival Times of Patients in
Korea.
PMID- 29966710
TI - Vitamin D deficiency and cardiovascular disease: Fact or fiction?
PMID- 29966711
TI - Chronic otitis media caused by Mycobacterium abscessus spp. massiliense treated
with tigecycline in a 10-year-old child.
AB - Mycobacterium abscessus is one of the most pathogenic and chemotherapy-resistant
rapidly growing mycobacteria. This Mycobacterium should always be considered as a
possible cause of chronic otitis media in children, and treatment might be
challenging because of its resistance to multiple antibiotics. There are no
reports describing the therapeutic use of tigecycline for the treatment of
chronic otitis media caused by M. abscessus. A 10-year-old boy was referred to
Tokyo Metropolitan Children's Medical Center with a 7-year history of recurrent
otitis media despite treatment with antibiotics and ventilation tubes. Cultures
of the otorrhea yielded Mycobacterium abscessus spp. massiliense, and it showed
multiple and high-level resistance. The boy required surgery and underwent
initial treatment with clarithromycin, amikacin, and tigecycline for 4 weeks. He
experienced emesis as a side-effect of tigecycline, which was well controlled
with ondansetron. He was treated successfully with 3 months of subsequent oral
clarithromycin and linezolid. This is the first pediatric case of chronic otitis
media caused by M. abscessus treated with a tigecycline-containing regimen.
Although the therapeutic use of tigecycline remains controversial, especially in
the pediatric population, it can be an acceptable option in the treatment of
chronic otitis media caused by M. abscessus.
PMID- 29966712
TI - Immigration Policy: Valuing Children.
PMID- 29966713
TI - Surgical Intervention in Patients with Tubo-Ovarian Abscess: Clinical Predictors
and a Simple Risk Score.
AB - STUDY OBJECTIVE: To identify the clinical characteristics associated with
surgical intervention in patients with tubo-ovarian abscess (TOA). DESIGN:
Retrospective cohort study (Canadian Task Force classification II-2). SETTING:
Tertiary university-affiliated hospital. PATIENTS: Three hundred thirty-five
patients were diagnosed with TOA based on sonographic and clinical criteria.
Patients who underwent surgical intervention were compared with patients managed
conservatively. INTERVENTION: Electronic medical records were used to identify
patients who were diagnosed with TOA between 2007 and 2015. All patients received
the same antibiotic regimen upon admission. The data extracted included microbial
and pathologic reports. Clinical characteristics such as disease severity and
outcomes were compared. The clinical predictors available on patient admission
for surgical intervention were identified retrospectively. A logistic regression
was used to determine the independent predictors of treatment failure. A risk
score was created by giving a nominal weight to each predictor. The score was
validated by a random bootstrap analysis. An additional validation cohort that
consisted of patients diagnosed with TOA during the 2 years after the original
study period was applied to the final score. MEASUREMENTS AND MAIN RESULTS: The
following variables of patients who underwent surgical intervention in comparison
with those successfully treated and were enrolled into the score analysis
differed significantly: age at admission (odds ratio [OR], 2.1; 95% confidence
interval [CI], 1.3-3.5), mean leukocytosis at admission (OR, 2.2; 95% CI, 1.3
3.6), ultrasonographic measurement of abscess diameter (OR, 3.6 95% CI, 2.0-6.3),
and the presence of bilateral abscess (OR, 2.2; 95% CI, 1.3-3.9). Risk groups A,
B, C, and D were positively correlated with the need for surgical intervention.
Those in the highest risk group D had an antibiotic failure rate of 92%, as
compared with those with the lowest risk group, in which there was a 20% risk of
antibiotic failure. CONCLUSIONS: Antibiotic treatment failure for TOA can be
predicted on patient admission using a novel risk assessment score.
PMID- 29966714
TI - Hematological Malignancies Associated With Primary Immunodeficiency Disorders.
AB - Primary Immunodeficiency disorders (PID) have been increasingly recognized in
association with hematologic malignancies. To better appreciate this association,
a systemic search of the Ovid MEDLINE database was performed with terms related
of hematologic malignancies and all PID described in the 2017 International Union
of Immunological Societies Expert Committee for Primary Immunodeficiency. More
than 60 PID distinct PID, caused by cell-intrinsic and extrinsic mechanisms were
associated with diverse hematologic malignancies. These occurred among all
subgroups of PID, including syndromic and non-syndromic combined PID affecting
cellular and humoral immunity, predominantly antibody deficiencies and defects of
immune regulation. In addition, defects in phagocyte numbers or functions, or in
innate immunity were associated with hematologic malignancies. Increased
awareness and vigilance for the possibility of malignancy is required when caring
for patients with PID.
PMID- 29966715
TI - CTLA-4 regulates human Natural Killer cell effector functions.
PMID- 29966717
TI - Contextual interference enhances motor learning through increased resting brain
connectivity during memory consolidation.
AB - Increasing contextual interference (CI) during practice benefits learning, making
it a desirable difficulty. For example, interleaved practice (IP) of motor
sequences is generally more difficult than repetitive practice (RP) during
practice but leads to better learning. Here we investigated whether CI in
practice modulated resting-state functional connectivity during consolidation. 26
healthy adults (11 men/15 women, age = 23.3 +/- 1.3 years) practiced two sets of
three sequences in an IP or RP condition over 2 days, followed by a retention
test on Day 5 to evaluate learning. On each practice day, functional magnetic
resonance imaging (fMRI) data were acquired during practice and also in a resting
state immediately after practice. The resting-state fMRI data were processed
using independent component analysis (ICA) followed by functional connectivity
analysis, showing that IP on Day 1 led to greater resting connectivity than RP
between the left premotor cortex and left dorsolateral prefrontal cortex (DLPFC),
bilateral posterior cingulate cortices, and bilateral inferior parietal lobules.
Moreover, greater resting connectivity after IP than RP on Day 1, between the
left premotor cortex and the hippocampus, amygdala, putamen, and thalamus on the
right, and the cerebellum, was associated with better learning following IP.
Mediation analysis further showed that the association between enhanced resting
premotor-hippocampal connectivity on Day 1 and better retention performance
following IP was mediated by greater task-related functional activation during IP
on Day 2. Our findings suggest that the benefit of CI to motor learning is likely
through enhanced resting premotor connectivity during the early phase of
consolidation.
PMID- 29966716
TI - Distinct neural processes for the perception of familiar versus unfamiliar faces
along the visual hierarchy revealed by EEG.
AB - Humans recognize faces with ease, despite the complexity of the task and of the
visual system which underlies it. Different spatial regions, including both the
core and extended face processing networks, and distinct temporal stages of
processing have been implicated in face recognition, but there is ongoing
controversy regarding the extent to which the mechanisms for recognizing a
familiar face differ from those for an unfamiliar face. Here, we used
electroencephalogram (EEG) and flicker SSVEP, a high signal-to-noise approach,
and searchlight decoding methods to elucidate the mechanisms mediating the
processing of familiar and unfamiliar faces in the time domain. Familiar and
unfamiliar faces were presented periodically at 15 Hz, 6 Hz and 3.75 Hz either
upright or inverted in separate blocks, with the rationale that faster
frequencies require shorter processing times per image and tap into fundamentally
different levels of visual processing. The 15 Hz trials, likely to reflect early
visual processing, exhibited enhanced neural responses for familiar over
unfamiliar face trials, but only when the faces were upright. In contrast,
decoding methods revealed similar classification accuracies for upright and
inverted faces for both familiar and unfamiliar faces. For the 6 Hz frequency,
familiar faces had lower amplitude responses than unfamiliar faces, and decoding
familiarity was more accurate for upright compared with inverted faces. Finally,
the 3.75 Hz frequency revealed no main effects of familiarity, but decoding
showed significant correlations with behavioral ratings of face familiarity,
suggesting that activity evoked by this slow presentation frequency reflected
higher-level, cognitive aspects of familiarity processing. This three-way
dissociation between frequencies reveals that fundamentally different stages of
the visual hierarchy are modulated by face familiarity. The combination of
experimental and analytical approaches used here represent a novel method for
elucidating spatio-temporal characteristics within the visual system.
PMID- 29966718
TI - Body mass variability is represented by distinct functional connectivity
patterns.
AB - Understanding weight-related differences in functional connectivity provides key
insight into neurocognitive factors implicated in obesity. Here, we sampled three
groups from human connectome project data: 1) 47 pairs of BMI-discordant twins (n
= 94; average BMI-discordancy 6.7 +/- 3.1 kg/m2), 2) 47 pairs of gender and BMI
matched BMI-discordant, unrelated individuals, and 3) 47 pairs of BMI-similar
twins, to test for body mass dependent differences in between network functional
connectivity. Across BMI discordant samples, three networks appeared to be highly
sensitive to weight status; specifically, a network comprised of gustatory
processing regions, a visual processing network, and the default mode network
(DMN). Further, in the BMI-discordant twin sample, twins with lower BMI had
stronger connectivity between striatal/thalamic and prefrontal networks (pFWE =
0.04). We also observed that individuals with a higher BMI than their twin had
stronger connectivity between cerebellar and insular networks (pFWE = 0.04).
Connectivity patterns observed in the BMI-discordant twin sample were not seen in
a BMI-similar sample, providing evidence that the results are specific to BMI
discordance. Beyond the involvement of gustatory and visual networks and the DMN,
little overlap in results were seen between the two BMI-discordant samples. In
concordance with previous findings, we hypothesize that stronger cortical
striatal-thalamic connectivity associated with lower body mass in twins may
facilitate increased regulation of hedonically motivated behaviors. In twins with
higher body mass, increased cerebellar-insula connectivity may be associated with
compromised satiation signaling, an interpretation dovetailing prior research.
The lack of overlapping results between the two BMI discordant samples may be a
function of higher study design sensitivity in the BMI-discordant twin sample,
relative to the more generalizable results in the unrelated sample. These
findings demonstrate that distinct connectivity patterns can represent weight
variability, adding to mounting evidence that implicates atypical brain
functioning with the accumulation and/or maintenance of elevated weight.
PMID- 29966719
TI - Reduced task durations in functional PET imaging with [18F]FDG approaching that
of functional MRI.
AB - INTRODUCTION: The brain's energy budget can be non-invasively assessed with
different imaging modalities such as functional MRI (fMRI) and PET (fPET), which
are sensitive to oxygen and glucose demands, respectively. The introduction of
hybrid PET/MRI systems further enables the simultaneous acquisition of these
parameters. Although a recently developed method offers the quantification of
task-specific changes in glucose metabolism (CMRGlu) in a single measurement,
direct comparison of the two imaging modalities is still difficult because of the
different temporal resolutions. Thus, we optimized the protocol and
systematically assessed shortened task durations of fPET to approach that of
fMRI. METHODS: Twenty healthy subjects (9 male) underwent one measurement on a
hybrid PET/MRI scanner. During the scan, tasks were completed in four blocks for
fMRI (4 * 30 s blocks) and fPET: participants tapped the fingers of their right
hand repeatedly to the thumb while watching videos of landscapes. For fPET,
subjects were randomly assigned to groups of n = 5 with varying task durations of
10, 5, 2 and 1 min, where task durations were kept constant within a measurement.
The radiolabeled glucose analogue [18F]FDG was administered as 20% bolus plus
constant infusion. The bolus increases the signal-to-noise ratio and leaves
sufficient activity to detect task-related effects but poses additional
challenges due to a discontinuity in the tracer uptake. First, three approaches
to remove task effects from the baseline term were evaluated: (1) multimodal,
based on the individual fMRI analysis, (2) atlas-based by removing presumably
activated regions and (3) model-based by fitting the baseline with exponential
functions. Second, we investigated the need to capture the arterial input
function peak with automatic blood sampling for the quantification of CMRGlu. We
finally compared the task-specific activation obtained from fPET and fMRI
qualitatively and statistically. RESULTS: CMRGlu quantified only with manual
arterial samples showed a strong correlation to that obtained with automatic
sampling (r = 0.9996). The multimodal baseline definition was superior to the
other tested approaches in terms of residuals (p < 0.001). Significant task
specific changes in CMRGlu were found in the primary visual and motor cortices
(tM1 = 18.7 and tV1 = 18.3). Significant changes of fMRI activation were found in
the same areas (tM1 = 16.0 and tV1 = 17.6) but additionally in the supplementary
motor area, ipsilateral motor cortex and secondary visual cortex. Post-hoc t
tests showed strongest effects for task durations of 5 and 2 min (all p < 0.05
FWE corrected), whereas 1 min exhibited pronounced unspecific activation. Percent
signal change (PSC) was higher for CMRGlu (~18%-27%) compared to fMRI (~2%). No
significant association between PSC of task-specific CMRGlu and fMRI was found (r
= 0.26). CONCLUSION: Using a bolus plus constant infusion protocol, the necessary
task duration for reliable quantification of task-specific CMRGlu could be
reduced to 5 and 2 min, therefore, approaching that of fMRI. Important for valid
quantification is a correct baseline definition, which was ideal when task
relevant voxels were determined with fMRI. The absence of a correlation and the
different activation pattern between fPET and fMRI suggest that glucose
metabolism and oxygen demand capture complementary aspects of energy demands.
PMID- 29966720
TI - The EADC-ADNI harmonized protocol for hippocampal segmentation: A validation
study.
AB - Recently, a group of major international experts have completed a comprehensive
effort to efficiently define a harmonized protocol for manual hippocampal
segmentation that is optimized for Alzheimer's research (known as the EADC-ADNI
Harmonized Protocol (the HarP)). This study compares the HarP with one of the
widely used hippocampal segmentation protocols (Pruessner, 2000), based on a
single automatic segmentation method trained separately with libraries made from
each manual segmentation protocol. The automatic segmentation conformity with the
corresponding manual segmentation and the ability to capture Alzheimer's disease
related hippocampal atrophy on large datasets are measured to compare the manual
protocols. In addition to the possibility of harmonizing different procedures of
hippocampal segmentation, our results show that using the HarP, the automatic
segmentation conformity with manual segmentation is also preserved (Dice's
kappa=0.88,kappa=0.87 for Pruessner and HarP respectively (p = 0.726 for common
training library)). Furthermore, the results show that the HarP can capture the
Alzheimer's disease related hippocampal volume differences in large datasets. The
HarP-derived segmentation shows large effect size (Cohen's d = 1.5883) in
separating Alzheimer's Disease patients versus normal controls (AD:NC) and medium
effect size (Cohen's d = 0.5747) in separating stable versus progressive Mild
Cognitively Impaired patients (sMCI:pMCI). Furthermore, the area under the ROC
curve for a LDA classifier trained based on age, sex and HarP-derived hippocampal
volume is 0.8858 for AD:NC, and for 0.6677 sMCI:pMCI. These results show that the
harmonized protocol-derived labels can be widely used in clinic and research, as
a sensitive and accurate way of delineating the hippocampus.
PMID- 29966721
TI - Beta-hydroxybutyrate Promotes the Expression of BDNF in Hippocampal Neurons under
Adequate Glucose Supply.
AB - Neurobiological evidence suggests that the ketone metabolite beta-hydroxybutyrate
(BHBA) exerts many neuroprotective functions for the brain. The previous study
revealed that BHBA could promote the expression of brain-derived neurotrophic
factor (BDNF) at glucose inadequate condition. Here we demonstrated that BHBA
administration induced the expression of BDNF in the hippocampus of mice fed with
normal diet. In vitro experiment results also showed that 0.02-2 mM BHBA
significantly increased BDNF expression in both the primary hippocampal neurons
and the hippocampus neuron cell line HT22 under adequate glucose supply. Bdnf
transcription induced by BHBA stimulus was mediated through the cAMP/PKA
triggered phosphorylation of CREB (S133) and the subsequent up-regulation of
histone H3 Lysine 27 acetylation (H3K27ac) binding at Bdnf promoters I, II, IV,
and VI. Moreover, BHBA stimulus induced a decrease in tri-methylation of H3K27
(H3K27me3) binding at the Bdnf promoters II and VI and the elevation of H3K27me3
specific demethylase JMJD3, which also contributed to the activation of Bdnf
transcription. These results demonstrated that BHBA within the physiological
range could promote BDNF expression in neurons via a novel signaling function.
Moreover, BHBA might possess more broad epigenetic regulatory activities, which
affected both the acetylation and demethylation of H3K27. Our findings reinforce
the beneficial effect of BHBA on the central nervous system (CNS) and suggest
that BHBA administration with no need for energy restriction might also be a
promising intervention to improve the neuronal activity and ameliorate the
degeneration of CNS.
PMID- 29966722
TI - The p38alpha MAPK Deletion in Oligodendroglia does not Attenuate Myelination
Defects in a Mouse Model of Periventricular Leukomalacia.
AB - Periventricular leukomalacia (PVL) is a severe type of white matter damage in
premature infants and the most common cause of cerebral palsy. It is generally
known to be caused by hypoxia and inflammation. Currently there is no effective
treatment available, in part due to that the pathogenesis of the disease has not
been well understood. The p38alpha mitogen-activated protein kinase (MAPK) is the
serine/threonine kinase and several in vitro studies demonstrated that p38 MAPK
is essential for oligodendroglial differentiation and myelination. Indeed, our
nerve/glial antigen 2 (NG2)-specific oligodendroglial p38alpha MAPK conditional
knockout (CKO) mice revealed its complex roles in myelination and remyelination.
To identify the specific in vivo roles of oligodendroglial p38alpha MAPK in PVL,
we generated a mouse PVL model by combination of LPS-mediated inflammation and
hypoxia-ischemia in NG2-p38alpha MAPK CKO mice. Our results demonstrate that a
selective deletion of p38alpha MAPK in oligodendrocyte did not attenuate
myelination defects in the mouse model of PVL. Myelination phenotype revealed by
MBP immunostaining was not significantly affected in the p38alpha MAPK CKO mice
compared to the wildtype after PVL induction. The electron microscopic images
demonstrated that the microstructure of myelin structures was not significantly
different between the wild-type and p38alpha MAPK CKO mice. In addition,
oligodendrocyte degeneration in the corpus callosum white matter area was
unaffected in the p38alpha MAPK CKO during and after the PVL induction. These
data indicate that p38alpha MAPK in oligodendrocyte has minimal effect on
myelination and oligodendrocyte survival in the mouse PVL model.
PMID- 29966723
TI - Up-regulation of NSP3 by Oligomeric Abeta Accelerates Neuronal Death Through Cas
independent Rap1A Activation.
AB - beta-Amyloid (Abeta) plays an important role in the early pathogenesis of
Alzheimer's disease (AD). In vitro studies have demonstrated that Abeta oligomers
induce hippocampal and neocortical neuronal death. However the neurotoxic
mechanisms by which soluble Abeta oligomers cause neuronal damage and death
remain to be fully elucidated. To this end, we analyzed the gene expression
profile of rat cerebral cortical neurons treated with Abeta oligomers in vitro.
Abeta treatment induced the expression of novel SH2-containing protein 3 (NSP3),
an adaptor molecule interacting with Cas family proteins. NSP3 expression was
upregulated not only in oligomeric-Abeta-treated cultured neurons but also in the
neocortex of aged Tg2576 mice. NSP3 overexpression in cultured cortical neurons
accelerated neuronal death. The C-terminal region of NSP3 unbound to a Cas
protein was necessary for the NSP3-induced acceleration of neuronal death, as was
Cas-independent Rap1A activation downstream of NSP3. Moreover, NSP3 RNAi
knockdown partially rescued Abeta-oligomer-treated neurons. These results
indicate that NSP3 upregulation by soluble Abeta oligomers may accelerate
neuronal death via Cas-independent Rap1A activation, implicating NSP3 in the
pathogenesis of AD.
PMID- 29966724
TI - Advanced Multimodal Methods for Cranial Pseudo-CT Generation Validated by IMRT
and VMAT Radiation Therapy Plans.
AB - PURPOSE: To investigate advanced multimodal methods for pseudo-computed
tomography (CT) generation from standard magnetic resonance imaging sequences and
to validate the results by intensity-modulated radiation therapy (IMRT) and
volumetric modulated arc therapy (VMAT) plans. We present 2 novel methods that
employ key techniques to enhance pseudo-CTs and investigate the effect on image
quality and applicability for IMRT and VMAT planning. MATERIALS AND METHODS: The
data set contains CT and magnetic resonance image scans from 15 patients who
underwent cranial radiation therapy. For each patient, pseudo-CTs of the head
were generated with a patch-based and a voxel-based algorithm. The accuracy of
the pseudo-CTs in comparison to clinical CTs was evaluated by mean absolute
error, bias, and the Dice coefficient (of bone). IMRT and VMAT plans were created
for each patient. Dose distributions were calculated with both the pseudo-CT and
the clinical CT scans and compared by gamma tests, dose-volume histograms, and
isocenter doses. RESULTS: The generated pseudo-CTs exhibited average mean
absolute errors of 118.7 +/- 10.4 HU for the voxel-based algorithm and 73.0 +/-
6.4 HU for the patch-based algorithm. The dose calculations were in good
agreement and showed gamma test (2 mm, 2%) pass rates for both beam setups (IMRT
and VMAT) of over 99% for 14 patients and over 98% for 1 patient. CONCLUSIONS: We
showed that the key techniques of our 2 novel algorithms advance the quality of
pseudo-CT significantly and generate very competitive pseudo-CTs compared with
previously published methods. This quality was confirmed by low dose error in
comparison to the ground-truth CT. With the achieved level of accuracy, our patch
based algorithm especially is a candidate for clinical routine use in IMRT and
VMAT planning.
PMID- 29966726
TI - Vegetable and fruit intake in Australian adolescents: Trends over time and
perceptions of consumption.
AB - The consumption of vegetables and fruit during adolescence is crucial to ensuring
adequate intake of the nutrients required to meet the rapid growth that
characterises this developmental period. However, significant reductions in
vegetable and fruit intake during adolescence have been observed making the
promotion of consumption an important health promotion challenge. To monitor
progress in this population segment toward meeting recommended intake levels and
identifying at-risk groups, the present study assessed changes in Australian
adolescents' vegetable and fruit consumption over time and identified the
demographic factors associated with meeting recommendations. As individuals who
are aware of their diet deficiencies are likely to be more receptive to healthy
eating interventions, the present study also assessed adolescents' perceptions of
the adequacy of their vegetable and fruit intake and identified the demographic
factors associated with correctly perceiving fruit and vegetable intake to be
inadequate. Two cross-sectional samples of Western Australian secondary school
students aged 12-17 years were surveyed in 2009-2010 (n = 1501) and 2012-2013 (n
= 1406). Only 14% of students at Wave 1 and 13% at Wave 2 met the recommended
guidelines for vegetable intake while 68% and 71% met the guidelines for fruit
intake. Females had significantly greater odds of failing to meet guidelines for
vegetable intake than males. Only 50% of students correctly identified their
vegetable and fruit intake to be inadequate. The observed very low levels of
compliance with vegetable intake recommendations suggest that addressing
deficiencies in vegetable consumption should be a primary focus of future
nutrition interventions. Efforts should also be made to increase adolescents'
perceptions of the inadequacy of their intake to optimise the effectiveness of
schemes designed to improve vegetable and fruit consumption in this population
segment.
PMID- 29966725
TI - The Use of Quantitative Imaging in Radiation Oncology: A Quantitative Imaging
Network (QIN) Perspective.
AB - Modern radiation therapy is delivered with great precision, in part by relying on
high-resolution multidimensional anatomic imaging to define targets in space and
time. The development of quantitative imaging (QI) modalities capable of
monitoring biologic parameters could provide deeper insight into tumor biology
and facilitate more personalized clinical decision-making. The Quantitative
Imaging Network (QIN) was established by the National Cancer Institute to advance
and validate these QI modalities in the context of oncology clinical trials. In
particular, the QIN has significant interest in the application of QI to widen
the therapeutic window of radiation therapy. QI modalities have great promise in
radiation oncology and will help address significant clinical needs, including
finer prognostication, more specific target delineation, reduction of normal
tissue toxicity, identification of radioresistant disease, and clearer
interpretation of treatment response. Patient-specific QI is being incorporated
into radiation treatment design in ways such as dose escalation and adaptive
replanning, with the intent of improving outcomes while lessening treatment
morbidities. This review discusses the current vision of the QIN, current areas
of investigation, and how the QIN hopes to enhance the integration of QI into the
practice of radiation oncology.
PMID- 29966727
TI - Establishing a food addiction diagnosis using the Yale Food Addiction Scale: A
closer look at the clinically significant distress/functional impairment
criterion.
AB - The concept of food addiction (FA) represents a set of problematic eating
behaviors related to overeating. According to the Yale Food Addiction Scale
(YFAS), which was based on the DSM-IV-TR substance dependence diagnostic
criteria, a FA diagnosis is assigned when at least three criteria and the
criterion evaluating clinically significant distress and/or functional impairment
are endorsed. Considering the decisive role of this last criterion, the present
study aimed to investigate its endorsement among individuals suffering from
severe obesity and awaiting bariatric surgery. A total of 146 individuals were
recruited at the Quebec Heart and Lung Institute and were invited to complete
various questionnaires. Differences between individuals who endorsed at least
three FA criteria and reported distress/impairment (FA+D/I; N = 24) and
individuals who endorsed at least three FA criteria but did not report
distress/impairment (FA-D/I; N = 27) were examined. Results revealed that 16% of
the total sample fulfilled a FA diagnosis when considering the clinically
significant distress/functional impairment criterion; however, this prevalence
rate climbed to 35% when removing the inclusion of distress/impairment.
Furthermore, individuals from the FA+D/I group showed more FA symptomatology and
hedonic hunger, but did not statistically differ from the FA-D/I group on
expected markers of psychological distress (depressive symptoms and quality of
life). Lastly, the experience of withdrawal symptoms and hedonic hunger were
found to be the best predictors of the endorsement of the distress/impairment
criterion. This study underlines the impact of this criterion in establishing a
FA diagnosis and highlights the importance of considering alternative ways to
interpret findings from the YFAS when dealing with clinical samples.
PMID- 29966728
TI - A latent class analysis of family eating habits in families with adolescents.
AB - The objectives of the present study were to identify adolescent classes based on
perceptions of their family's eating habits and to determine whether these
classes differ in terms of family meal frequency and source, parents and
adolescent diet quality, nutritional status, satisfaction with life, family life
and food-related life. Questionnaires were administered to a sample of 300 two
parent families with one child between 10 and 17 years in Chile. Questionnaires
included the Satisfaction with Life Scale (SWLS), the Satisfaction with Food
related Life scale (SWFoL), the Satisfaction with Family Life scale (SWFaL) and
the Adapted Healthy Eating Index (AHEI). Adolescents also answered the Family
Eating Habits Questionnaire (FEHQ). Latent class (LC) analysis was used to
estimate the number of classes associated with the adolescent's perceptions about
their family's eating habits, based on the three factors detected in the FEHQ.
The LC analysis yielded three classes: "medium cohesion around family
meals/healthy food-related parenting practices" (Class 1, 50.4%), "high cohesion
around family meals/healthy food-related parenting practices" (Class 2, 25.9%)
and "high cohesion around family meals/unhealthy food-related parenting
practices" (Class 3, 23.7%). Classes also differed in the adolescents AHEI score,
frequency and source of family meals; body mass index, SWLS and SWFaL scores in
mothers, fathers and adolescents, adolescent sex and household financial
situation. These findings suggest that frequent and cohesive family meals improve
the well-being in both parents and adolescents, but are not enough to achieve
healthier diets and weight statuses in adolescents.
PMID- 29966729
TI - GRADEing the un-GRADE-able: a description of challenges in applying GRADE methods
to the ethical and implementation questions of pediatric organ donation
guidelines.
AB - Good practice statements (GPSs) have been proposed by the GRADE working group as
a way of avoiding the inappropriate characterization of evidence as low quality
in support of strong recommendations justified by indirect evidence. This
commentary examines how the GPS methodology was applied to the development of a
recent guideline for pediatric deceased donation after circulatory determined
death. This guideline was informed by a broad body of indirect literature and
addressed a variety of social, legal, and ethical questions in addition to
several implementation issues. While the resulting document contained a vast
majority of GPS (63 as opposed to seven actionable GRADEd recommendations), we
maintain that this application was appropriate to develop recommendations within
the GRADE framework. This commentary explores how GPS may be applied in this
context and explores whether a new classification of recommendations focused on
these types of issues may be appropriate.
PMID- 29966730
TI - Mixed-methods research revealed the need for dementia services and Human Resource
Master Plan in an aging Philippines.
AB - OBJECTIVE: To determine the status of dementia care services and workforce in
selected public and private hospitals and geriatric care facilities in the
Philippines. STUDY DESIGN AND SETTING: Framework analysis of 54 key informant
interviews, 4 focus group discussions, and survey of 167 workers in 26
purposively selected facilities. RESULTS: Three dementia care models emerged: (1)
separate unit, seen in 2 facilities, (2) partial dementia services, 9 facilities,
and (3) integrated with the general services, 15 facilities. Only 1 of 26
facilities had specific outpatient services; only 1 provided care exclusively to
dementia patients. Community day care services were rare. Physicians, nurses, and
nursing assistants were available in all institutions. Nutrition and physical
therapy services were generally available. There was a scarcity of physician
specialists (e.g., geriatrics) and occupational therapists. Half of the workers
surveyed rated the quality of their service at 80 or higher, 27% defined dementia
correctly. Attitude toward dementia was very positive, in the form of willingness
to care for and willingness to learn more. CONCLUSION: Mixed-methods research
helped identify service and health workforce needs and elucidate understanding of
health workers' attitude and perceptions toward a disease of which there is low
knowledge and awareness.
PMID- 29966731
TI - A survey of Delphi panelists after core outcome set development revealed positive
feedback and methods to facilitate panel member participation.
AB - OBJECTIVES: The objective of this study was to elicit feedback on consensus
methodology used for core outcome set (COS) development. STUDY DESIGN AND
SETTING: An online survey of international Delphi panelists participating in a
recent COS for clinical research studies evaluating acute respiratory failure
(ARF) survivors was conducted. Panelists represented 14 countries (56% outside
the United States). RESULTS: Seventy (92%) panelists completed the survey,
including 32 researchers, 19 professional association representatives, 4 research
funding representatives, and 15 ARF survivors/caregiver members. Among
respondents, 91% reported that the time required to participate was appropriate
and 96% were not bothered by reminders for timely response. Attributes of
measurement instruments and voting results from previous rounds were evaluated
differently across stakeholder groups. When measurement properties were explained
in the stem of the survey question, 59 (84%) panelists (including 73% of
survivors/families) correctly interpreted information about an instrument's
reliability. Without a reminder in the stem, only 20 (29%) panelists (including
38% of researchers) correctly identified properties of a COS. CONCLUSION: This
international Delphi panel, including >20% patients/caregivers, favorably
reported on feasibility of the methodology. Providing all panelists pertinent
information/reminders about the project's objective at each voting round is
important to informed decision making across all stakeholder groups.
PMID- 29966732
TI - Patients and investigators prefer measures of absolute risk in subgroups for
pragmatic randomized trials.
AB - OBJECTIVES: Pragmatic randomized trials are important tools for shared decision
making, but no guidance exists on patients' preferences for types of causal
information. We aimed to assess preferences of patients and investigators toward
causal effects in pragmatic randomized trials. STUDY DESIGN AND SETTING: We (a)
held three focus groups with patients (n = 23) in Boston, MA; (b) surveyed (n =
12) and interviewed (n = 5) investigators with experience conducting pragmatic
trials; and (c) conducted a systematic literature review of pragmatic trials (n =
63). RESULTS: Patients were distrustful of new-to-market medications unless
substantially more effective than existing choices, preferred stratified absolute
risks, and valued adherence-adjusted analyses when they expected to adhere.
Investigators wanted both intention-to-treat and per-protocol effects but felt
methods for estimating per-protocol effects were lacking. When estimating per
protocol effects, many pragmatic trials used inappropriate methods to adjust for
adherence and loss to follow-up. CONCLUSION: We made four recommendations for
pragmatic trials to improve patient centeredness: (1) focus on superiority in
effectiveness or safety, rather than noninferiority; (2) involve patients in
specifying a priori subgroups; (3) report absolute measures of risk; and (4)
complement intention-to-treat effect estimates with valid per-protocol effect
estimates.
PMID- 29966733
TI - Biochemical characterization of venom from Pseudoboa neuwiedii (Neuwied's false
boa; Xenodontinae; Pseudoboini).
AB - In this work, we examined the proteolytic and phospholipase A2 (PLA2) activities
of venom from the opisthoglyphous colubrid Pseudoboa neuwiedii. Proteolytic
activity (3 and 10 MUg of venom) was comparable to that of Bothrops neuwiedii
venom but less than Bothrops atrox. This activity was inhibited by EDTA and 1,10
phenanthroline but only slightly affected (<=30% inhibition) by PMSF and AEBSF,
indicating it was mediated by snake venom metalloproteinases (SVMPs). The pH and
temperature optima for proteolytic activity were 8.0 and 37 degrees C,
respectively. The venom had no esterase activity, whereas PLA2 activity was
similar to B. atrox, greater than B. neuwiedii but less than B. jararacussu. SDS
PAGE revealed venom proteins >100 kDa, 45-70 kDa, 21-24 kDa and ~15 kDa, and mass
spectrometry of protein bands revealed SVMPs, cysteine-rich secretory proteins
(CRISPs) and PLA2, but no serine proteinases. In gelatin zymography, the most
active bands occurred at 65-68 kDa (seen with 0.05-0.25 MUg of venom).
Caseinolytic activity occurred at 50-66 kDa and was generally weaker than
gelatinolytic activity. RP-HPLC of venom yielded 15 peaks, five of which showed
gelatinolytic activity; peak 7 was the most active and apparently contained a P
III class SVMP. The venom showed alpha-fibrinogenase activity, without affecting
the beta and gamma chains; this activity was inhibited by EDTA and 1,10
phenanthroline. The venom did not clot rat citrated plasma but reduced the rate
and extent of coagulation after plasma recalcification. In conclusion, P.
neuwiedii venom is highly proteolytic and could potentially affect coagulation in
vivo by degrading fibrinogen via SVMPs.
PMID- 29966735
TI - Oleanolic acid improves diet-induced obesity by modulating fat preference and
inflammation in mice.
AB - Obesity, triggered by high-fat diet (HFD), is associated to altered gustatory
perception of dietary lipids. Oleanolic acid (OLA), a triterpene, has been
reported to exert anti-obesity effects in animal models. Hence, we investigated
the role of OLA in the modulation of oro-sensory perception of lipids in control
and HFD-induced obese mice. As expected, OLA-treated obese mice exhibited a
decrease in body, liver, and visceral adipose tissue weights. OLA treatment
improved glucose tolerance, insulin level, plasma lipopolysaccharide (LPS), and
hepatic cholesterol and triglyceride concentrations. OLA-treated obese mice
exhibited higher fat preference compared to untreated obese mice, probably due to
the increase in mRNA encoding CD36, a fat taste receptor, in mouse taste bud
cells (mTBC). This phenomenon was associated with fatty-acid induced increases in
free intracellular calcium concentrations, [Ca2+]i, induced in mTBC from OLA
treated obese mice. OLA also influenced the expression of mRNA encoding pro
inflammatory cytokines (IL-1beta and IL-6) and some lipogenic genes (PPARalpha,
SREBP1, FAS, ChREBP, and G6Pase) in liver and adipose tissue. These findings
reveal that OLA improves gustatory perception of lipids and exerts protective
effects in obesity.
PMID- 29966734
TI - G-quadruplex virtual drug screening: A review.
AB - Over the past two decades biologists and bioinformaticians have unearthed
substantial evidence supporting a role for G-quadruplexes as important mediators
of biological processes. This includes telomere damage signaling, transcriptional
activity, and splicing. Both their structural heterogeneity and their abundance
in oncogene promoters makes them ideal targets for drug discovery. Currently,
there are hundreds of deposited DNA and RNA quadruplex atomic structures which
have allowed researchers to begin using in silico drug screening approaches to
develop novel stabilizing ligands. Here we provide a review of the past decade of
G-quadruplex virtual drug discovery approaches and campaigns. With this we
introduce relevant virtual screening platforms followed by a discussion of best
practices to assist future G4 VS campaigns.
PMID- 29966736
TI - Mesoporous silica nanoparticles facilitating the dissolution of poorly soluble
drugs in orodispersible films.
AB - Orodispersible films (ODF) are immediately dissolving/disintegrating intraoral
dosage forms, presented as substitutes of conventional tablets or capsules to
ease problems associated with swallowing. Efforts have been made to be able to
exploit ODFs as dosage forms for poorly soluble drugs. In the last two decades,
mesoporous silica nanoparticles (MSNs) have been extensively used in drug
delivery applications to overcome solubility problems of drugs. The tunable
features of MSNs make them suitable candidates as drug carriers and solubility
enhancers. In this study, the feasibility of MSNs as a carrier of poorly soluble
drugs, using prednisolone as a model drug, in ODFs was investigated. Our results
revealed that the increased amount of MSNs in ODFs leads to shortening of the
disintegration time of the films. Drug content investigations showed that low
dose ODFs with prednisolone incorporation efficiencies higher than 80% could be
produced. Furthermore, the prednisolone release profile from ODFs can be tuned
with the incorporation of MSNs as drug carrier (MSNpred). The MSNpred
incorporated ODFs yield with immediate release of drug from the ODF, whereby 90%
of the prednisolone content could be released in the first minutes. By modifying
the MSNpred design with copolymer surface coating, prednisolone (cop-MSNpred)
release can be modulated into a two-step sustained release profile. To sum up,
the MSNs platform does not only provide careful low dose incorporation into ODF
with high efficiency, but it also aids in tuning the drug release profiles from
ODFs.
PMID- 29966737
TI - Phytosome complexed with chitosan for gingerol delivery in the treatment of
respiratory infection: In vitro and in vivo evaluation.
AB - Respiratory infection is a viral spreading disease and a common issue,
particularly in kids. The treatments are available but have so many limitations
because the drawback of this disease is more morbidity and mortality in the
severely immune compromised. Even, the phyto-constituent antibacterial drug
Gingerol was selected to treat respiratory infection but it exhibits low
bioavailability profile, less aqueous-solubility issue and most important is
rapidly eliminated from the body. To overcome these problems, novel drug delivery
(nanoparticle) based phytosome complexed with chitosan approach was implemented.
In this research work, the phytosome (GP) was prepared by blending of gingerol
with soya lecithin in organic solvent using anti-solvent precipitation technique
and it was further loaded in the aqueous solution of chitosan to formulate the
phytosome complexed with chitosan (GLPC). To optimize the formulations of
gingerol, it was characterized for percentage yield, percentage entrapment
efficiency, drug loading and particle size, physical compatibility studies etc.
which demonstrated the confirmation of complex of GLPC with soya lecithin and
chitosan. The % entrapment efficiency and % drug loading of GLPC was found (86.02
+/- 0.18%, 08.26 +/- 0.72%) and of GP (84.36 +/- 0.42%, 08.05 +/- 0.03%),
respectively. The average particle size and zeta potential of GLPC and GP were
254.01 +/- 0.05 nm (-13.11 mV), and 431.21 +/- 0.90 nm (-17.53 mV), respectively
which confirm the inhibition of particle aggregation by using chitosan in
complex. The in vitro release rate of GP (86.03 +/- 0.06%) was slower than GLPC
(88.93 +/- 0.33%) in pH 7.4 phosphate buffer up to 24 h by diffusion process
(Korsmeyer Peppas model). The optimized GLPC and GP were shown irregular particle
shapes & spherical and oval structures with smooth surface by SEM analysis.
Furthermore, GLPC has shown the potent in vitro antioxidant activity, susceptible
antibacterial activity and effective anti-inflammatory activity as compared to GP
against stress, microbial infection and inflammation which were causable reason
for the respiratory infections. GLPC has improved the significant bioavailability
and also correlated the hematological values on rabbit blood against the
incubation of microorganisms. Thus, the prepared nanoparticle based approach to
deliver the gingerol, has the combined effect of chitosan and phytosome which
shown better sustained-release profile and also prolonging the oral absorption
rate of gingerol with effective antibacterial activity to treat respiratory
infection.
PMID- 29966738
TI - Adult rat morphine exposure changes morphine preference, anxiety, and the brain
expression of dopamine receptors in male offspring.
AB - Addiction to drugs, including opioids is the result of an interplay between
environmental and genetic factors. It has been shown that the progeny of addict
people is at higher risk for drug addiction. However, the mechanisms of such
trans-generational effects of drugs are not so clear. Here we have evaluated the
effects of parental morphine consumption on anxiety, morphine preference, and
mRNA expression of dopamine receptors in F1 and F2 male offspring. Morphine was
chronically administered to adult male and female Wistar rats followed by 14-day
abstinence before mating. Morphine preference and anxiety-like behavior in the
offspring were measured by two-bottle-choice paradigm and elevated-plus maze,
respectively. Real-time PCR was used to measure the mRNA expression level of
dopamine receptors in the striatum, nucleus accumbens, prefrontal cortex, and
hippocampus of F1 animals. The results indicated that F1 but not the F2 male
progeny of morphine-exposed parents had a greater preference for morphine, and
more anxiety-like behavior compared to the offspring of saline-treated parents.
In F1 male progeny of morphine-treated parents, D1 and D5 dopamine receptors were
significantly increased in the prefrontal cortex and nucleus accumbens. D5 and D2
receptors were decreased in the hippocampus. D4 dopamine receptor was augmented
in striatum and hippocampus and decreased in the prefrontal cortex. Adulthood
exposure to chronic morphine in male and female rats before conception leads to
higher morphine preference and increased anxiety in F1 but not F2 male progeny.
Alterations of dopamine receptor expression in the reward system may be one
mechanism responsible for observed changes in F1 offspring.
PMID- 29966739
TI - Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido
inflammatory stress in rat model of autism.
AB - Prenatal exposure to valproic acid (VPA) induces behavioral disorders and
enhancement of oxido-inflammatory stress in Autism Spectrum Disorders (ASDs). The
aim of this study was to investigate the comparative effects of hesperetin (Hst)
and nano-hesperetin on social behavior deficits and oxido-inflammatory indexes in
prenatally valproic acid-exposed rat offspring. Pregnant Wistar rats on embryonic
day 0 (E0) were segregated into six groups; Group-1 served as vehicle, received
distillated water orally (PO) from E1 until the end of lactation and saline
intraperitoneally (i.p) on E12.5. Group-2 received sodium valproate (500 mg/kg in
0.9% saline, i.p) on E12.5 was considered as VPA-exposed group, Group-3 to 6 were
VPA-exposed which received hesperetin and nano-hesperetin (10 and 20 mg/kg/day,
PO) from E0 until the end of lactation respectively. Social interaction and open
field tests were conducted on postnatal day 28 (PND 28) and PND 30, cerebral
antioxidant enzymes activity and biochemical indexes, the level of inflammatory
factors in plasma and histopathology of cerebellum were estimated on PND 28 and
PND 30. Prenatal valproic acid-exposed rat exhibited poor sociability and high
level of anxiety-like behaviors (P < 0.05). In addition, increased level of
oxidative stress and inflammation were found by determining different oxido
inflammatory markers. Hesperetin and nano-hesperetin treatment improved the
behavioral disorder and reduced the oxidative stress in brain and significantly
(p < 0.05) plasma's inflammation indexes. In conclusion, it can be state that
nano-hesperetin exerts neuroprotective action in comparison with hesperetin and
could be efficacious for treatment of VPA animal model of autism during pregnancy
and lactation.
PMID- 29966740
TI - Frankincense upregulates the hippocampal calcium/calmodulin kinase II-alpha
during development of the rat brain and improves memory performance.
AB - BACKGROUND: Frankincense is an oleo gum resin derived from trees of genus
Boswellia. It has favorable effects on memory formation. However, the probable
underlying molecular mechanisms have not been assessed. Frankincense exerts some
of its effects via activation of protein kinases. Calcium/calmodulin kinaseII
(CaMKII) and CaMKIV are crucial mediators of learning and memory. We studied the
effect of maternal injection of the aqueous extract of frankincense during
gestation and lactation periods on spatial memory performance and the mRNA
expression levels of the hippocampal CaMKIIand CaMKIV in the offspring rats.
METHODS: Aqueous extract of Frankincense (50 and 100 mg/kg) or tap water was
gavaged to distinct female rats during gestation and lactation periods. Memory
performance was assessed in groups of male offspring using Morris water maze. In
other groups of the offspring (with no memory test), the hippocampi of the
juvenile rats were removed 30 days after labor. A real-time PCR method was used
to measure the mRNA levels of CaMKII and CaMKIV. RESULTS: Frankincense improved
spatial memory retrieval in the offspring rats in a dose-dependent manner. The
mRNA expression of hippocampal CaMKIV was unchanged between groups. However, the
mRNA expression of hippocampal CaMKII was dose-dependently upregulated in the
rats, whose mothers had received frankincense. CONCLUSIONS: Due to the crucial
role of the CaMKII in memory formation, the results provide a molecular basis for
the effect of administration of frankincense to mother rats on improvement of the
memory in the offspring.
PMID- 29966741
TI - Prenatal undernutrition decreases the anorectic response to septic doses of
lipopolysaccharides in adulthood in male rats.
AB - Prenatal undernutrition affects some physiological functions after birth, and
such changes are associated with the pathogenesis of various diseases. Recently,
we have reported that prenatally undernourished male rats exhibited stronger
febrile and anorectic responses to immune stress induced by moderate-dose
lipopolysaccharide (LPS) treatment in adulthood. In the present study, we
evaluated the effects of prenatal undernutrition on stress responses to the
administration of a septic dose (3 mg/kg) of LPS in later life, mainly focusing
on changes in hypothalamic proinflammatory cytokine expression. We also evaluated
the expression of hypothalamic and peripheral reproductive factors because it has
been suggested that the stress responses of reproductive functions are affected
by prenatal and neonatal stress and nutritional conditions. As a result, we found
that prenatal undernutrition attenuated the anorectic response to septic-dose LPS
treatment in adulthood in male rats. In addition, it attenuated the LPS-induced
suppression of serum testosterone levels and the changes in hypothalamic
proinflammatory cytokine (interleukin (IL)-1beta, tumor necrosis factor-alpha,
and IL-6) expression induced by septic-dose LPS treatment in adulthood. These
results suggest that prenatal undernutrition attenuates stress and reproductive
responses under severe immune stress conditions. The downregulation of
hypothalamic stress-related factor expression might be involved in such
attenuated stress responses, which could be one of the protective mechanisms used
to prevent excessive immune responses and aid survival.
PMID- 29966742
TI - Hierarchical supramolecular platelets from hydrophobically-modified
polysaccharides and alpha-cyclodextrin: Effect of hydrophobization and alpha
cyclodextrin concentration on platelet formation.
AB - Micro- and nano-platelets are a group of particles with typical flat surfaces and
hexagonal shape. They are obtained by hierarchical self-assembly in water of
alpha-cyclodextrin and polysaccharides hydrophobically-modified with alkyl
chains. It is expected that the formation of well structured and cohesive
platelets is driven by the interaction between alkyl chains grafted on
polysaccharides and alpha-cyclodextrin. The objective of this investigation is to
tune platelet formation by modifying these two parameters, independently on
polysaccharide composition. A systematic study was conducted by varying
polysaccharide type (dextran, pullulan, amylopectin), degree of substitution
(DS:0.1-5.6%) and alpha-cyclodextrin concentration (0-10 wt%) for a fixed
concentration of polysaccharide esterified with palmitoyl groups (1 wt%).
Characterizations include ATR-FTIR, elemental analysis, solid state 13C NMR and
transmission electron microscopy. Abundant and well-organized hexagonal platelets
were obtained with high DS (4.2-5.6%) and a concentration of alpha-cyclodextrin
higher than 2.5 wt%. Isothermal titration calorimetry revealed a sequential
binding with a stoichiometry of 2 alpha-cyclodextrin molecules for 1 palmitoyl
group grafted on dextran. This is the first report showing the possibility to
control platelet formation by modifying DS and alpha-cyclodextrin concentration,
independently on polysaccharide composition.
PMID- 29966743
TI - Design-oriented regression models for H2O2 decontamination processes in sterile
drug product manufacturing considering rapidity and sterility.
AB - We developed regression models for designing rapid and effective H2O2
decontamination processes in the manufacturing of sterile drug products such as
injectables. Decontamination, which is typically performed by using H2O2, is a
critical changeover process used to establish a sterile environment for filling
products. In the process, there is a trade-off relationship between the duration
of the process and the level of sterility assurance that needs to be considered
in the design. Our model defines these two items as objective functions and the
parameters describing the profile of H2O2 injection and the initial humidity as
design variables. Our model also considers aeration, i.e., removal of H2O2 from
the environment, as a part of the entire process. This design-oriented modeling
considering the entire process is the novelty of the work. Experiments were
performed using an industrial isolator to develop and validate a set of
regression models that describe the relationship between the design variables and
the objective functions. In the application of the model, Pareto-optimal
conditions could be indicated given the target H2O2 concentration in aeration,
which is useful for the makers of drugs and/or isolators for designing
decontamination processes.
PMID- 29966744
TI - Mediterranean essential oils as precious matrix components and active ingredients
of lipid nanoparticles.
AB - Essential oils are recognized as valuable active pharmaceutical ingredients
attributed to a set of biological properties, which include antibacterial,
antifungal, antiviral, antioxidant, anticancer, immune-modulatory, analgesic and
anti-inflammatory activities. Their use in pharmaceutics is however compromised
by their limited water solubility and low physicochemical stability (i.e.
volatility, oxidation). In order to overcome these limitations, we aimed to
develop nanostructured lipid carriers (NLC) as delivery systems for Mediterranean
essential oils, in particular Rosmarinus officinalis L., Lavandula x intermedia
"Sumian", Origanum vulgare subsp. hirtum and Thymus capitatus essential oils,
selected on the basis of their antioxidant and anti-inflammatory activities. NLC
composed of Softisan (as solid lipid) have been produced by phase inversion
temperature (PIT) and high-pressure homogenization (HPH), using two different
emulsifiers systems. Particles have been further characterized for their mean
particle size, polydispersity, zeta potential, morphology and chemical
interactions. Best NLC formulations were obtained with Kolliphor/Labrafil as
surfactants, and using Rosmarinus, Lavandula and Origanum as essential oils (PDI
between 0.126 and 0.141, Zave < 200 nm). Accelerated stability studies have also
been carried out to estimate the effect of the production method and surfactant
composition on the long-term stability of EOs-loaded NLC. In vitro biological
cell viability and anti-inflammatory activities were evaluated in Raw 264.7 cells
(macrophage cell line), while in vitro antioxidant activity was checked by DPPH
assay. Lavandula and Rosmarinus NLC were shown to be the most biocompatible
formulations up to a concentration of 0.1% (v/v), whereas they were able to
induce a dose-dependent anti-inflammatory activity in the order Lavandula >
Rosmarinus >= Origanum.
PMID- 29966745
TI - The pharmacological treatment of chronic comorbidities in COPD: mind the gap!
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is commonly associated
with other chronic diseases, which poses several diagnostic and therapeutic
problems. Indeed, important comorbidities frequently remain unrecognized and,
then, untreated, whereas respiratory drugs may have non respiratory side effects,
and selected non respiratory drugs may variably affect the respiratory function.
OBJECTIVE: to describe: how COPD affects the presentation and contributes to the
diagnostic challenges of its most common comorbidities; how coexisting COPD
impacts the therapeutic approach to selected comorbidities and viceversa.
METHODS: we distinguish comorbidities of COPD depending upon whether they are
complications of COPD or share risk factors, mainly smoke, with it or, finally,
aggravate COPD. We describe atypical presentations of and diagnostic clues to
comorbidities and suggest screening procedures. Finally, the main therapeutic
problems, as resulting from the risk of untoward effects of therapies of COPD and
its comorbidity, with special attention to drug-drug interactions and possible
overdosages, are described. RESULTS: selected complications of COPD, such as
osteoporosis, sarcopenia and dysphagia, are rarely recognized and treated, likely
due to the poor awareness of them. Important comorbidities, such as coronary
artery disease, chronic heart failure, obstructive sleep apnoea syndrome and
chronic renal failure, also should be systematically searched for because of
their commonly variant presentation. Disease-related symptoms should be
distinguished from drug effects or drug-drug interaction effects. CONCLUSIONS: a
truly comprehensive view of the complex COPD patient, hopefully capitalizing on
multidimensional geriatric assessment, is needed to dissect the many components
of health status impairment and to provide the optimal care. Selected screening
procedures are highly desirable to identify frequently missed comorbidities.
Pharmacosurveillance is an essential part of the approach to COPD and its
comorbidities.
PMID- 29966746
TI - Patient representation learning and interpretable evaluation using clinical
notes.
AB - We have three contributions in this work: 1. We explore the utility of a stacked
denoising autoencoder and a paragraph vector model to learn task-independent
dense patient representations directly from clinical notes. To analyze if these
representations are transferable across tasks, we evaluate them in multiple
supervised setups to predict patient mortality, primary diagnostic and procedural
category, and gender. We compare their performance with sparse representations
obtained from a bag-of-words model. We observe that the learned generalized
representations significantly outperform the sparse representations when we have
few positive instances to learn from, and there is an absence of strong lexical
features. 2. We compare the model performance of the feature set constructed from
a bag of words to that obtained from medical concepts. In the latter case,
concepts represent problems, treatments, and tests. We find that concept
identification does not improve the classification performance. 3. We propose
novel techniques to facilitate model interpretability. To understand and
interpret the representations, we explore the best encoded features within the
patient representations obtained from the autoencoder model. Further, we
calculate feature sensitivity across two networks to identify the most
significant input features for different classification tasks when we use these
pretrained representations as the supervised input. We successfully extract the
most influential features for the pipeline using this technique.
PMID- 29966747
TI - Re-defining kinetic lung overload: Time for new paradigms.
AB - This paper compares two previously published 13-week inhalation studies with
poorly soluble, low-toxicity particles (PSLTs) in rats to identify the unifying
key metric of kinetic lung overload. The PSLTs compared are Multi-Walled Carbon
Nanotubes (MWCNT) and black iron oxide (Fe3O4, magnetite). Their material
densities and related displacement volumes differ approximately 30-fold. This
offers an opportunity for analyzing the impact of the PSLT-density of
agglomerates on endpoints currently conceived to be involved in kinetic lung
overload. Corpuscular volumes and counts of cells retrieved by bronchoalveolar
lavage (BAL) are analyzed to interrelate modeled cumulative lung burdens of solid
aerosol to predict the no observed adverse effect concentration (NOAEC) and range
of conditions causing various degrees of kinetic lung overload up to and beyond
the maximum tolerated cumulative dose (MTD). Both descriptors are a reflection of
accumulated lung burdens and, by design, bracket repeated exposure inhalation
studies with PSLTs. This comparative analysis of high- and low-density PSLTs
reveals that the leading adverse outcome pathway (AOP) is caused by a markedly
increased pool-size of BAL-cells rather than any increased corpuscular volume of
cells. The overload-related increased pool-size of BAL-cells is shown to be the
dependent variable for the prorated increased elimination half-time of PSLTs.
This interrelationship was used to predict the exposure concentrations for
attaining a NOAEC and MTD of guideline-based repeated exposure inhalation studies
with PSLTs. Earlier approaches suggesting a loss of the migratory capabilities of
particle-laden, enlarged alveolar macrophages to be the cause for any increased
elimination half-time of PSLTs could not be confirmed. In summary, kinetic
modeling provides a versatile means to predict the cornerstones of repeated
inhalation studies with PSLTs on rats. Such possibilities leverage adjustment of
studies from different sources to identical degrees of kinetic overload. They
also facilitate and foster AOP-facilitated read-across approaches. The course
taken enables risk assessors to better differentiate lung pathologies caused by
generic lung overload and substance-specific pathologies.
PMID- 29966748
TI - Prenatal caffeine exprosure increases adult female offspring rat's susceptibility
to osteoarthritis via low-functional programming of cartilage IGF-1 with histone
acetylation.
AB - Our previous in vivo studies showed that prenatal caffeine exposure (PCE) could
restrain the development of chondrogenesis, which may delay fetal articular
cartilage development and increase susceptibility to osteoarthritis in adults.
So, the goal of the current study is to clarify theincreasing susceptibility to
adult osteoarthritis in caffeine-exposed female offspring and its'mechanism.
Pregnant rats were treated with 120 mg/kg.d caffeine or equal volumes of saline
from gestational day (GD) 9 to 20. knee joints were collected from GD20 female
fetuses and 18-week old female offspring which was treated with strenuous running
for 6 weeks (55 min/day at 20 m/min) load to induce osteoarthritis. Knee joints
from GD20 fetuses and adult offspring were collected for histochemistry and
immunohistochemistry. Next, chondrocytes were isolated from 1-day-old newborn
rats and in vitro studies were conducted where the cells in primary culture were
exposed to 1, 10, and 100 MUM caffeine and 250, 500, and 1,250 nM corticosterone.
Insulin-like growth factor 1 (IGF-1) signal pathway genes' expression levels in
fetal chondrocytes were studied, and IGF-1 histone acetylation was detected in
vitro. Immunohistochemical results showed low expression levels of IGF-1
signaling genes (IGF-1, IRS-1, AKT, and COL2A1) both in fetal and adult cartilage
with PCE. For adult offspring, histological results and Mankin score revealed
increased cartilage destruction and accelerated osteoarthritis progression in PCE
group with strenuous running exercise. Analysis in vitro revealed that caffeine
and corticosterone impeded the expression of IGF-1 signaling pathway aggrecan and
COL2A1 genes, but only corticosterone decreased H3K9 and H3K27 acetylation in the
IGF-1 promoter region. In concluson, PCE low functional programmed cartilage IGF
1 by histone acetylation modification via overexposure to corticosterone and
delayed articular cartilage development from fetus to adults. Then, the delayed
cartilage development increased susceptibility to osteoarthritis in offsprings.
PMID- 29966749
TI - Blood-brain barrier regulation in psychiatric disorders.
AB - The blood-brain barrier (BBB) is a dynamic interface between the peripheral blood
supply and the cerebral parenchyma, controlling the transport of material to and
from the brain. Tight junctions between the endothelial cells of the cerebral
microvasculature limit the passage of large, negatively charged molecules via
paracellular diffusion whereas transcellular transportation across the
endothelial cell is controlled by a number of mechanisms including transporter
proteins, endocytosis, and diffusion. Here, we review the evidence that
perturbation of these processes may underlie the development of psychiatric
disorders including schizophrenia, autism spectrum disorder (ASD), and affective
disorders. Increased permeability of the BBB appears to be a common factor in
these disorders, leading to increased infiltration of peripheral material into
the brain culminating in neuroinflammation and oxidative stress. However,
although there is no common mechanism underpinning BBB dysfunction even within
each particular disorder, the tight junction protein claudin-5 may be a
clinically relevant target given that both clinical and pre-clinical research has
linked it to schizophrenia, ASD, and depression. Additionally, we discuss the
clinical significance of the BBB in diagnosis (genetic markers, dynamic contrast
enhanced-magnetic resonance imaging, and blood biomarkers) and in treatment (drug
delivery).
PMID- 29966751
TI - The cerebellum as a movement sensor.
AB - In this article, we review a broad range of studies of cerebellar function and
dysfunction and interpret them within the framework that the cerebellum acts as
part of a mechanism of predictive control. We describe studies that span human
behaviour and consider the motor and sensory impairments that result from
cerebellar damage. We conclude that a parsimonious explanation of cerebellar
function is as a predictor of the sensory outcomes of movement. However, future
studies are needed to more rigorously test this hypothesis and determine how the
cerebellar circuit might perform this type of computation.
PMID- 29966750
TI - Autophagy mediators (FOXO1, SESN3 and TSC2) in Lewy body disease and aging.
AB - Neurodegenerative disorders such as Parkinson's disease (PD) and dementia with
Lewy bodies (DLB) are characterized by impairment of autophagy. Cellular survival
is dependent on efficient clearance of phosphorylated alpha-synuclein, which
accumulates as fibrils in the neuronal cytoplasm as Lewy bodies (LBs). The
forkhead box O 1 (FOXO1) is a member of the FOXO family that functions in various
intracellular processes including regulation of autophagy. Transcriptional
activation of FOXO1 has been reported to initiate autophagy by inhibiting the
expression of Mechanistic Target of Rapamycin (mTOR), mediated by sestrin 3
(SESN3) and tuberous sclerosis complex 2 (TSC2). Although many autophagy-related
proteins are known to be incorporated into LBs, no report has documented the
involvement of these autophagy modulators (FOXO1, SESN3 and TSC2) in the
pathogenesis of PD and DLB. In the present study, we performed immunostaining and
Western blot analysis using the brains of normal controls and patients with PD
and DLB in order to clarify the involvement of FOXO1, SESN3 and TSC2 in LBs. Our
study demonstrated for the first time the presence of FOXO1, SESN3 and TSC2 in
brainstem-type LBs. The expression levels of these proteins in the brain did not
differ between the normal controls and patients with PD or DLB. We further
utilized mice model to investigate the effect of alpha-synuclein overexpression
on these proteins, and found that TSC2 was significantly increased in alpha
synuclein transgenic mice relative to wild type mice at 9 weeks of age, but not
at 30 weeks of age. Together with expression data showing gradual increase of
these molecules with age in wild type mice, these findings suggest that autophagy
modulators are incorporated into LBs and that the expression of these proteins
can be increased by various factors including aging.
PMID- 29966752
TI - ERK1/2 inhibition increases dopamine release from differentiated PC12 cells.
AB - The release of dopamine (DA) is one of the main steps in the control of neuronal
functioning and all CNS. It was demonstrated that many factors such as protein
kinases and synaptic proteins are tightly involved in the regulation of DA
secretion, but the data are contradictory. Here we analysed an effect of ERK1/2
inhibition on DA secretion from differentiated PC12 cells and evaluated the
correlation between the activity of kinases/synaptic proteins and the level of
released DA. PC12 cells were differentiated by NGF for 6 days. On the 7th day the
cells were incubated for 1, 2 and 4 h with 10MUM U0126. Obtained data
demonstrated a significant accumulation of DA in the media after 4 h incubation
with U0126 that accompanied with upregulation of PKG activity. Analysis of
exocytosis proteins demonstrated decreased phosphorylation level of synapsin I
and content of SNAP25. Taken together our data proposed an inhibitory role of
ERK1/2 in the regulation of catecholamine secretion and demonstrated that balance
between PKG and ERK1/2 activity could have a substantial impact on the regulation
of DA release from the cells.
PMID- 29966753
TI - The influence of age in women in visuo-spatial memory in reaching and navigation
tasks with and without landmarks.
AB - Spatial memory and navigation capabilities tend to decline in normal aging, but
few studies have assessed the impact of landmarks on route learning in a large
scale environment. The objectives were to examine age-related effects on visuo
spatial working memory capabilities in various environments and to determine the
impact of landmarks in navigation skills in normal aging. 42 young women (23.6 +/
4.9 years) and 37 older women (70.7 +/- 4.7 years) with no cognitive impairment
have performed three visuo-spatial working memory tests: one in reaching space
(computerized Corsi-Block-Tapping test) and two in locomotor navigation space (a
condition without landmarks: Virtual Walking Corsi Test and a condition with
landmarks: Virtual Room Walking Test). A two-way mixed ANOVA test showed that the
young subjects performed better in all conditions than older subjects. The
performance in visuo-spatial working memory thus decreases with age. Visuo
spatial working memory performances were identical in reaching and navigation
spaces for both groups. The integration of landmarks into a navigational task
decreases performance in older women, while this performance is not altered in
younger women.
PMID- 29966754
TI - beta-eudesmol, an oxygenized sesquiterpene, affects efferent adrenal sympathetic
nerve activity via transient receptor potential ankyrin 1 in rats.
AB - The autonomic nervous system innervates various peripheral tissue functions.
Various external stimuli affect autonomic nerve activity, however, there is
little information about the involvement of sensory receptors in the responses.
The TRPA1 is a calcium-permeable non-selective cation channel which plays a
crucial role in the susceptibility to various stimuli. beta-Eudesmol, an
oxygenated sesquiterpene found in hop essential oil and beer, activates the
TRPA1. Intragastric administration of beta-eudesmol decreased efferent adrenal
sympathetic nerve activity (ASNA) in rats, whereas subcutaneous administration
did not. ASNA suppression by beta-eudesmol was not observed in TRPA1 knockout
rats. The beta-eudesmol derived ASNA suppression was partially, but
significantly, eliminated by subdiaphragmatic vagotomy in rats, suggesting the
afferent vagal nerve from the gastrointestinal tract to the brain is involved in
the effect of beta-eudesmol on ASNA. Our results indicate that beta-eudesmol
suppresses ASNA, partly through TRPA1 and the afferent vagus nerve. These
findings introduce the physiological significance of the TRPA1 in the control of
ASNA.
PMID- 29966755
TI - Interaction of obesity with smoking and inflammatory arthropathies increases the
risk of periprosthetic joint infection: a propensity score matched study in a
Chinese Han population.
AB - BACKGROUND: Although a large number of studies have identified obesity as an
independent risk factor for the development of periprosthetic joint infection
(PJI), the synergistic impacts of obesity with other factors on PJI remain
unknown. Additionally, few studies have specifically explored the risk factors of
PJI within a Chinese population. AIMS: To investigate the association between
obesity and PJI in a Chinese population, and identify synergistic impacts of
obesity with other risk factors on the development of PJI. METHODS: Three hundred
and seven patients at a single institution with a diagnosis of PJI following
primary total hip or knee arthroplasty, treated from 2008 to 2015, were
identified. Each case was matched with two controls who did not develop PJI after
primary total hip or knee arthroplasty in the study period using propensity score
matching for several important parameters. Multi-variable logistic regression
models were used to estimate the association between body mass index (BMI) and
the risk of developing PJI. Interaction and stratified analyses were conducted
according to age, sex, type of surgery, smoking status, alcohol use, diabetes,
inflammatory arthritis, liver disease and renal disease. FINDINGS: The multiple
logistic analyses showed that obesity was associated with increased risk of PJI
[odds ratio (OR) 2.48; 95% confidence interval (CI) 1.66-3.69]. When analysed as
a continuous variable, BMI was also associated with increased risk of PJI (OR per
1 kg/m2 increase in BMI 1.08; 95% CI 1.02-1.14). In the interaction analysis,
patients who were obese and smoked had a higher OR of developing PJI than non
smokers who were obese (OR 3.54 vs 1.55, P-value for interaction=0.031).
Similarly, the OR was much higher for patients with both obesity and inflammatory
arthritis than for patients who were obese with no history of inflammatory
arthritis (OR 3.9 vs 1.55, P-value for interaction=0.029). No other significant
interactions were found in the association between obesity and PJI. CONCLUSION:
Obesity is an independent risk factor for the development of PJI in the Chinese
Han population. Surgeons should be aware that obese patients who smoke or have
inflammatory arthritis are at additional increased risk of PJI.
PMID- 29966756
TI - Desiccation tolerance is associated with Staphylococcus aureus
hypertransmissibility, resistance and infection development in the operating
room.
AB - BACKGROUND: Desiccation tolerance increases Staphylococcus aureus survival and
risk of transmission. A better understanding of factors driving intraoperative
transmission of S. aureus pathogens may lead to innovative improvements in
intraoperative infection control. AIMS: To determine whether desiccation
tolerance is associated with intraoperative S. aureus transmission, and to
examine typical transmission dynamics for desiccation-tolerant isolates in the
operating room in order to provide the impetus for development of improved
intraoperative infection control strategies. METHODS: S. aureus isolates (N=173)
were collected from anaesthesia work area reservoirs in 274 operating room
environments. Desiccation tolerance was assessed and the potential association
with sequence type (ST) and clonal transmission was evaluated. Whole cell genome
analysis and pulsed-field gel electrophoresis analysis were used to compare
desiccation-tolerant isolates with causative organisms of infection. FINDINGS: S.
aureus ST 5 isolates had greater desiccation tolerance than all other
intraoperative STs [ST 5, N=34, median Day 2 colony-forming unit (cfu) survival
0.027% +/- 0.029%; other STs, N=139, median Day 2 cfu survival 0.0091% +/- 1.41%;
corrected P=0.0001]. ST 5 was associated with increased risk of clonal
transmission (relative risk 1.82, 95% confidence interval 1.23-2.71, P=0.003). ST
5 transmission was linked by whole cell genome analysis to postoperative
infection. CONCLUSIONS: Increased desiccation tolerance is associated with
intraoperative transmission of S. aureus ST 5 isolates that are linked to
postoperative infection. Future work should determine whether attenuation of
desiccation-tolerant, intraoperative ST 5 strains can impact the incidence of
healthcare-associated infections.
PMID- 29966757
TI - Development of consensus-based national antimicrobial stewardship competencies
for UK undergraduate healthcare professional education.
AB - BACKGROUND: Healthcare professionals are involved in an array of patient- and
medicine-related stewardship activities, for which an understanding and
engagement with antimicrobial stewardship (AMS) is important. Undergraduate
education provides an ideal opportunity to prepare healthcare professionals for
these roles and activities. AIM: To provide UK national consensus on a common set
of antimicrobial stewardship competencies appropriate for undergraduate
healthcare professional education. METHODS: A modified Delphi approach comprising
two online surveys delivered to a UK national panel of 21 individuals reflecting
expertise in prescribing and medicines management with regards to the education
and practice of nurses and midwives, pharmacists, physiotherapists, and
podiatrists; and antimicrobial prescribing and stewardship. Data collection took
place between October and December 2017. FINDINGS: A total of 21 participants
agreed to become members of the expert panel, of whom 19 (90%) completed round 1
questionnaire, and 17 (89%) completed round 2. Panelists reached a consensus,
with consistently high levels of agreement reached, on six overarching competency
statements (subdivided into six domains), and 55 individual descriptors essential
for antimicrobial stewardship by healthcare professionals. CONCLUSION: Due to the
consistently high levels of agreement reached on competency statements and their
associated descriptors, this competency framework should be used to direct
education for undergraduate healthcare professionals, and those working in new
clinical roles to support healthcare delivery where an understanding of, and
engagement with, AMS is important. Although the competencies target basic
education, they can also be used for continuing education.
PMID- 29966758
TI - The response of pre-osteoblasts and osteoclasts to gallium containing mesoporous
bioactive glasses.
AB - : Mesoporous bioactive glasses (MBGs) in the system SiO2-CaO-P2O5-Ga2O3 have been
synthesized by the evaporation induced self-assembly method and subsequent
impregnation with Ga cations. Two different compositions have been prepared and
the local environment of Ga(III) has been characterized using 29Si, 71Ga and 31P
NMR analysis, demonstrating that Ga(III) is efficiently incorporated as both,
network former (GaO4 units) and network modifier (GaO6 units). In vitro
bioactivity tests evidenced that Ga-containing MBGs retain their capability for
nucleation and growth of an apatite-like layer in contact with a simulated body
fluid with ion concentrations nearly equal to those of human blood plasma.
Finally, in vitro cell culture tests evidenced that Ga incorporation results in a
selective effect on osteoblasts and osteoclasts. Indeed, the presence of this
element enhances the early differentiation towards osteoblast phenotype while
disturbing osteoclastogenesis. Considering these results, Ga-doped MBGs might be
proposed as bone substitutes, especially in osteoporosis scenarios. STATEMENT OF
SIGNIFCANCE: Osteoporosis is the most prevalent bone disease affecting millions
of patients every year. However, there is a lack of bone grafts specifically
designed for the treatment of bone defects occurred because of osteoporotic
fractures. The consequence is that osteoporotic bone defects are commonly treated
with the same biomaterials intended for high quality bone tissue. In this work we
have prepared mesoporous bioactive glasses doped with gallium, demonstrating
osteoinductive capability by promoting the differentiation of pre-osteoblast
toward osteoblasts and partial inhibition of osteoclastogenesis. Through a deep
study of the local environment of gallium within the mesoporous matrix, this work
shows that gallium release is not required to produce this effect on osteoblasts
and osteoclasts. In this sense, the presence of this element at the surface of
the mesoporous bioactive glasses would be enough to locally promote bone
formation while reducing bone resorption.
PMID- 29966759
TI - Effect of age on biomaterial-mediated in situ bone tissue regeneration.
AB - : Emerging studies show the potential application of synthetic biomaterials that
are intrinsically osteoconductive and osteoinductive as bone grafts to treat
critical bone defects. Here, the biomaterial not only assists recruitment of
endogenous cells, but also supports cellular activities relevant to bone tissue
formation and function. While such biomaterial-mediated in situ tissue
engineering is highly attractive, success of such an approach relies largely on
the regenerative potential of the recruited cells, which is anticipated to vary
with age. In this study, we investigated the effect of the age of the host on
mineralized biomaterial-mediated bone tissue repair using critical-sized cranial
defects as a model system. Mice of varying ages, 1-month-old (juvenile), 2-month
old (young-adult), 6-month-old (middle-aged), and 14-month-old (elderly), were
used as recipients. Our results show that the bio-mineralized scaffolds support
bone tissue formation by recruiting endogenous cells for all groups albeit with
differences in an age-related manner. Analyses of bone tissue formation after 2
and 8 weeks post-treatment show low mineral deposition and reduced number of
osteocalcin and tartrate-resistant acid phosphatase (TRAP)-expressing cells in
elderly mice. STATEMENT OF SIGNIFICANCE: Tissue engineering strategies that
promote tissue repair through recruitment of endogenous cells will have a
significant impact in regenerative medicine. Previous studies from our group have
shown that biomineralized materials containing calcium phosphate minerals can
contribute to neo-bone tissue through recruitment and activation of endogenous
cells. In this study, we investigated the effect of age of the recipient on
biomaterial-mediated bone tissue repair. Our results show that the age of the
recipient mouse had a significant impact on the quality and quantity of the
engineered neo-bone tissues, in which delayed/compromised bone tissue formation
was observed in older mice. These findings are in agreement with the clinical
observations that age of patients is a key factor in bone repair.
PMID- 29966760
TI - Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of
Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and
Myelodysplastic Syndrome.
AB - Increasing donor-recipient HLA disparity is associated with negative outcomes of
allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative
relevance amid non-HLA donor characteristics is not well established. We
addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany
for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were
HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA
mismatched unrelated (<10/10 MMUD, n = 790). Overall survival (OS) was similar
after MRD compared with 10/10 MUD HSCT, reflecting opposing hazards of relapse
(hazard ratio [HR], 1.32; P < .002) and nonrelapse mortality (HR, .63; P < .001).
After UD HSCT, increasing HLA disparity was associated with inferior OS (HR, 1.21
[P < .02] and HR, 1.57 [P < .001] for 9/10 and <=8/10 MMUD, respectively,
compared with 10/10 MUD). Among non-HLA donor characteristics, age, sex
mismatching (male recipient-female donor), and cytomegalovirus (CMV) mismatching
(positive recipient-negative donor) impacted OS. Multivariate subgroup analysis
showed that OS was similar after HSCT from the youngest 9/10 MMUD (<30 years)
compared with the oldest 10/10 MUD (>40 years) (HR, 1.18; P = .25) and also in
male patients transplanted from female 10/10 MUD compared with male 9/10 MMUD
(HR, .89; P = .46). In contrast, OS of CMV-positive patients tended to be better
with CMV-negative 10/10 MUDs compared with CMV-positive 9/10 MMUDs (HR, 1.31; P =
.04). Because of low patient numbers in subgroups, definite conclusions and
establishment of a hierarchy among HLA matching and non-HLA donor characteristics
could not be made. Our data suggest that the impact of donor age and sex mismatch
but not CMV mismatch on outcome of allogeneic HSCT may be comparable with that of
single HLA disparity.
PMID- 29966761
TI - Translation of Clinical Research into Practice: An Impact Assessment of the
Results from the Blood and Marrow Transplant Clinical Trials Network Protocol
0201 on Unrelated Graft Source Utilization.
AB - Barriers and facilitators to adoption of results of clinical trials are
substantial and poorly understood. We sought to examine whether the results of
the randomized, multicenter Blood and Marrow Transplant Clinical Trials Network
(BMT CTN) 0201 study comparing peripheral blood (PB) with bone marrow (BM) stem
cells for unrelated donor (URD) hematopoietic cell transplantation (HCT) changed
practice from PB to BM graft utilization and explored factors that impact graft
selection and translation of research results into practice. The difference
between use of URD BM and PB in the 2 years before and after publication of
results in 2012 was examined using observational data collected by the Center for
Blood and Marrow Transplant Research. A web-based survey of transplant physicians
was conducted to understand the change in physician-reported personal and center
preferred URD graft. No significant change in use of BM versus PB grafts occurred
after 2012. Both BMT CTN participating and nonparticipating centers continued to
use PB. Ninety-two percent of respondents were aware of the study results; 18%
reported a change in personal and 16% reported a change in their center's
practice of requesting BM instead of PB for URD HCT. Patient characteristics and
the perception that engaging local champions to increase the evidence uptake were
factors associated with personal or center change in practice. Despite awareness
of the trial results, fewer than one-fifth of HCT physicians reported practice
change in response to the BMT CTN 0201 results. Observational data confirmed no
discernible change in practice.
PMID- 29966762
TI - Tau/DDX6 interaction increases microRNA activity.
AB - Tauopathies, such as Alzheimer's disease, are characterized by intracellular
aggregates of insoluble Tau proteins. Originally described as a microtubule
binding protein, recent studies demonstrated additional physiological roles for
Tau. The fact that a single protein can regulate multiple cellular functions has
posed challenge in terms of understanding mechanistic cues behind the pathology.
Here, we used tandem-affinity purification methodology coupled to mass
spectrometry to identify novel interaction partners. We found that Tau interacts
with DDX6, a DEAD box RNA helicase involved in translation repression and mRNA
decay as well as in the miRNA pathway. Our results demonstrate that Tau increases
the silencing activity of the miRNA let-7a, miR-21 and miR-124 through DDX6.
Importantly, Tau mutations (P301S, P301L) found in the inherited tauopathies,
frontotemporal dementia and parkinsonism linked to chromosome 17, disrupt
Tau/DDX6 interaction and impair gene silencing by let-7a. Altogether, these data
demonstrated a new unexpected role for Tau in regulating miRNA activity.
PMID- 29966763
TI - An exon three-way junction structure modulates splicing and degradation of the
SUS1 yeast pre-mRNA.
AB - The SUS1 gene of Saccharomyces cerevisiae is unusual as it contains two introns
and undergoes alternative splicing, retaining one or both introns depending on
growth conditions. The exon located between the two introns can be skipped during
splicing and has been detected in circular form. This exon (E2) has also been
found to influence the splicing of the flanking introns, an unusual situation in
budding yeast where splicing mainly relies on intron recognition. Using SHAPE
(selective 2'-hydroxyl acylation analyzed by primer extension), NMR spectroscopy,
gel electrophoresis and UV thermal denaturation experiments combined with
computational predictions, we show that E2 of SUS1 comprises a conserved double
helical stem topped by a three-way junction. One of the hairpins emerging from
the junction exhibited significant thermal stability and was capped by a purine
rich loop structurally related to the substrate loop of the VS ribozyme. Cellular
assays revealed that three mutants containing altered E2 structures had impaired
SUS1 expression, and that a compensatory mutation restoring the conserved stem
recovered expression to wild-type levels. Semi-quantitative RT-PCR measurements
paralleled these results, and revealed that mutations in E2 altered splicing and
transcript degradation processes. Thus, exon structure plays an important role in
SUS1 RNA metabolism.
PMID- 29966764
TI - Enhancer-driven transcriptional regulation is a potential key determinant for
human visceral and subcutaneous adipocytes.
AB - Obesity is characterized by the excess of body fat leading to impaired health.
Abdominal fat is particularly harmful and is associated with cardiovascular and
metabolic diseases and cancer. In contrast, subcutaneous fat is generally
considered less detrimental. The mechanisms that establish the cellular
characteristics of these distinct fat types in humans are not fully understood.
Here, we explored whether differences of their gene regulatory mechanisms can be
investigated in vitro. For this purpose, we in vitro differentiated human
visceral and subcutaneous pre-adipocytes into mature adipocytes and obtained
their gene expression profiles and genome-wide H3K4me3, H3K9me3 and H3K27ac
patterns. Subsequently, we compared those data with public gene expression data
from visceral and subcutaneous fat tissues. We found that the in vitro
differentiated adipocytes show significant differences in their transcriptional
landscapes, which correlate with biological pathways that are characteristic for
visceral and subcutaneous fat tissues, respectively. Unexpectedly, visceral
adipocyte enhancers are rich on motifs for transcription factors involved in the
Hippo-YAP pathway, cell growth and inflammation, which are not typically
associated with adipocyte function. In contrast, enhancers of subcutaneous
adipocytes show enrichment of motifs for common adipogenic transcription factors,
such as C/EBP, NFI and PPARgamma, implicating substantially disparate gene
regulatory networks in visceral and subcutaneous adipocytes. Consistent with the
role in obesity, predominantly the histone modification pattern of visceral
adipocytes is linked to obesity-associated diseases. Thus, this work suggests
that the properties of visceral and subcutaneous fat tissues can be studied in
vitro and provides preliminary insights into their gene regulatory processes.
PMID- 29966765
TI - Analysis of Reptarenavirus genomes indicates different selective forces acting on
the S and L segments and recent expansion of common genotypes.
AB - Reptarenaviruses, a genus of snake-infecting viruses belonging to the family
Arenaviridae, have bi-segmented genomes. The long (L) segment encodes the Z and L
(RNA polymerase) proteins, whereas the short (S) segment codes for the
glycoprotein precursor (GPC) and for the nucleoprotein (NP). Presently,
reptarenaviruses have only been described in captive snakes. In these animals,
mixed infections are common and most infected reptiles harbor multiple S and/or L
segment genotypes. Within single animals, L segments are more genetically diverse
than S segments and one S segment genotype (S6) was detected in the majority of
snakes. Whether the unbalanced L to S segment ratio is due to stochastic events,
to distinct replication/packaging efficiencies, or to differential selective
pressure is presently unknown. We addressed these open questions by analyzing the
ancient and recent evolutionary history of reptarenavirus genomes. Results
indicated that purifying selection shaped the bulk of reptarenavirus coding
sequences, although selective constraint was stronger for NP and L compared to
GPC. During the divergence of reptarenavirus genomes, episodic positive selection
contributed to the evolution of the viral polymerase, an observation that
parallels those on mammarenaviruses. Population genetics analyses indicated that
the most common S and L segment genotypes (including S6) display markedly
negative Tajima's D values, but not low nucleotide diversity, suggesting recent
population expansion. In conclusion, our data indicate that the selective
pressures were stronger for the L segment than for the S segment, at least during
reptarenavirus genotype divergence. More recently, the population sizes of some L
and S segment genotypes expanded, suggesting that they out-competed the other
genotypes, which show D values consistent with constant or decreasing population
size. Competition among segments may have driven the disappearance of some S
segment genotypes from wild and/or captive snake populations, eventually leading
to the observed L to S imbalance.
PMID- 29966766
TI - Reality check: Can transplanting more renal dialysis patients buy us an MRI
scanner?
PMID- 29966767
TI - Cutaneous Mycobacterium Chelonae infection in a patient with Rheumatoid Arthritis
treated with glucocorticoids.
PMID- 29966768
TI - Inpatient rheumatology consultation for gout flares and advice to initiate urate
lowering treatment (ULT) in hospital discharge summary increases ULT prescription
in primary care.
PMID- 29966769
TI - Angioimmunoblastic T-cell lymphoma mimicking eosinophilic granulomatosis with
polyangiitis (Churg-Strauss).
PMID- 29966770
TI - Costovertebral arthritis revealing spondyloarthritis.
PMID- 29966771
TI - Psychological Factors Associated With Ultramarathon Runners' Supranormal Pain
Tolerance: A Pilot Study.
AB - Athletes seem to have higher pain tolerance than the normally active population.
It is unknown whether psychological factors contribute to their supranormal pain
tolerance. The aim of this pilot study was to examine pain-related psychological
processes in ultramarathon runners ('ultrarunners') and to explore whether
psychological factors mediate the elevated pain tolerance displayed by
ultrarunners. Forty participants took part in the study: 20 ultrarunners and 20
age- and gender-matched controls. Participants underwent the cold pressor test
using water cooled to 0.1 to 0.5 degrees C and completed the Pain Catastrophizing
Scale, Pain Anxiety Symptoms Scale-20, Pain Vigilance and Awareness
Questionnaire, and Pain Resilience Scale. Immersion time on the cold pressor test
was significantly longer for the ultrarunners (P = .007) and they also had lower
scores on all Pain Anxiety Symptoms Scale-20 subscales (P <= .030). The 2 groups
did not differ significantly on the other questionnaires. Mediation analysis
revealed that reduced pain-related escape and avoidance behaviors accounted for
40% of the difference in immersion time between the groups (P = .020). Our
results suggest that ultrarunners have lower levels of pain-related anxiety than
the general population and that their supranormal pain tolerance is partially
mediated by reduced pain-related escape and avoidance behaviors. PERSPECTIVE:
This study investigated whether psychological factors contribute to the
supranormal pain tolerance displayed by ultrarunners. It found that ultrarunners
have lower levels of pain-related anxiety than nonrunning controls and that
reduced pain-related escape and avoidance behaviors partially mediate their
elevated pain tolerance.
PMID- 29966772
TI - Persistent Post-Mastectomy Pain: Risk Factors and Current Approaches to
Treatment.
AB - Persistent Post-Mastectomy Pain (PPMP) is a common condition that can follow
surgeries for breast cancer, the most common cancer in women. Because of the
frequency of PPMP and its potential severity, it has received increasing research
attention. This manuscript reviews the recent research literature, beginning with
a brief history and then relevant medical, surgical, demographic, and
psychosocial risk factors. Subsequently, social, psychological, and functional
sequelae that have been linked to PPMPS are considered, as is research on current
pharmacological, psychological, and rehabilitative approaches to treatment. The
review concludes with a discussion of directions for future research and
treatment that might reduce the incidence and impact of PPMP on breast cancer
survivors. PERSPECTIVE: This article describes current research literature
involving mechanisms, risks, and treatments related to persistent post-mastectomy
pain. Implications of research findings also are discussed for pre- and post
surgical approaches to pain management, current treatments, and promising
research directions.
PMID- 29966774
TI - Dietary restriction alters the fatbody transcriptome during immune responses in
Bombyx mori.
AB - Dietary restriction (DR) leads to extended lifespan in many species ranging from
yeasts to mammal, and it can also affect the immune system to some extent.
Herein, we investigated whether DR can enhance the immunity of Bombyx mori
suffering from acute pathogenic microorganism infection. The results showed that
DR could accelerate the melanisation reaction, delay the early death in
silkworms, meanwhile Staphylococcus aureus (SA) load was lower in the early stage
of infection. Moreover, more immune-related genes were identified to be down
regulated in the DR group infected with SA compared with the ad libitum - fed
(AL) group infected with SA through mRNA deep sequencing (RNAseq) and
quantitation PCR. We speculate that rapid melanization may beneficial to the
lower SA load and delay the time point of the early death, and the lower SA load
may lead to many immune-related DEGs were down-regulated. These results may help
us to understand the mechanisms by which DR affects the immune system in insects
and other animals.
PMID- 29966773
TI - Host plant-derived allelochemicals and metal components are associated with
oxidative predominance and antioxidant plasticity in the larval tissues of
silkworm, Antheraea mylitta: Further evidence of joint effects hypothesis.
AB - Tasar silkworm, Antheraea mylitta is a polyphagous insect that primarily feeds on
Terminalia arjuna, Terminalia tomentosa and Shorea robusta. However, larval
rearing on S. robusta results in poor performance for the reasons unexplored.
Oxidative burden imposed by host plants is presumed to be a determining factor
for larval fitness. With this hypothesis we have analyzed the foliar constituents
of the respective host plants, the levels of oxidative stress and antioxidant
protection in the larval tissues in response to their altered feeding on
different host plants for different durations (2 and 10 days). Results indicate
that S. robusta leaves contain the highest amount of tannin and redox active
metals compared to those of other host plants. Consequently, hemolymph and midgut
tissues of the larvae shifted to S. robusta exhibited oxidative predominance.
Increased activities of superoxide dismutase, catalase and glutathione S
transferase in the larval tissues indicated an adaptive response to host plant
driven oxidative assault. Our in vitro study also strongly supplements the in
vivo findings indicating S. robusta foliages as a strong inducer of lipid
peroxidation (LPx). Copper and Iron were found to be more potent in inducing LPx
in the midgut tissues of the larvae compared to Zinc and Manganese. This study
for the first time demonstrates the combined implications of host plant derived
allelochemicals and elements on oxidative stress and antioxidant plasticity in
this insect. The overall findings also brace up the newly emerging concept on
joint effects hypothesis (organic and elemental defence) for enhanced plant
defence.
PMID- 29966775
TI - Morphologic Variations of the Collateral Sulcus on the Mediobasal Region of the
Temporal Lobe: An Anatomical Study.
AB - OBJECTIVE: The fusiform gyrus and the collateral sulcus are the anatomical
structures located in the temporobasal region. In this study, the topographic
anatomy of the fusiform gyrus and the collateral sulcus is detailed to make a
contribution for a successful course of temporal lobe surgery. METHODS: We
studied the basal surface of the temporal lobes of 38 formalin-fixed adult human
brain specimens. In the morphometric analysis, the distance between anterior and
posterior transverse collateral sulcus and the distance between the
occipitotemporal sulcus and fusiform apex were used as parameters. The
topographic anatomy of collateral sulcus was identified in detail, and 4 sulcal
patterns were used to classify the sulcal arrangement of basal surface of
temporal lobe in each hemisphere: type 1, single-branch and unbroken collateral
sulcus with no connection; type 2, continuous with the rhinal sulcus; type 3,
continuous with the occipitotemporal sulcus and; type 4, continuous with both
rhinal and occipitotemporal sulcus. RESULTS: The current study showed that type 1
was the pattern seen most frequently (42.1%, 16/38), whereas type 4 was the least
(7.9%, 3/38). Overall, 63.2% (12/19) of subjects had the same sulcal pattern in
both temporal lobes. The morphometric analysis showed that the mean distance
between anterior and posterior transverse collateral sulcus was 50 +/- 16.2 mm
and the mean distance between occipitotemporal sulcus and fusiform apex was 26 +/
8.4 mm. CONCLUSIONS: The topographic anatomy of the collateral sulcus with its
surrounding structures is detailed in this study. This study clarifies and
supplements the knowledge presently available to help develop a more feasible
surgical concept.
PMID- 29966776
TI - Childhood Lhermitte-Duclos Disease Progressing to Medulloblastoma in Bilateral
Cerebellar Hemispheres: Report of Unusual Case.
AB - BACKGROUND: Lhermitte-Duclos disease is an extremely rare pathologic entity
characterized by a cerebellar mass composed of enlarged cerebellar folia
containing abnormal ganglion cells. This entity usually presents in young and
middle-aged adults and rarely in children. There is no study in the literature
analyzing the long-term clinical course of this disease to assess the behavior
primarily because of its rarity. CASE DESCRIPTION: We present our experience with
a 7-year-old patient of Lhermitte-Duclos disease who was followed up for 5 years
and found to have progressed to bilateral World Health Organization grade IV
medulloblastoma. This case denotes the malignant potential of this rare disorder.
CONCLUSIONS: LDD is seen rarely and demands a high degree of suspicion in
patients presenting with cerebellar mass and/or imaging characteristics. It is
prudent to keep these patients in close follow-up for early detection of
malignant transformation.
PMID- 29966777
TI - Transsphenoidal Surgery for Elderly Patients with Acromegaly and Its Outcomes:
Comparison with Younger Patients.
AB - BACKGROUND: Elderly patients with acromegaly who have comorbidities may
increasingly encounter perioperative complications; however, little data are
available on the risks and outcomes of surgical treatment in these patients. We
aimed to analyze and compare the results of transnasal transsphenoidal surgery
(TTS) in elderly and younger patients. METHODS: Eighty-seven consecutive patients
with acromegaly who underwent TTS were included. We divided the patients into
elderly (>=65 years) and younger (<65 years) groups and compared clinical
characteristics, anesthesia risk, and surgical outcomes in these 2 groups.
RESULTS: The 87 patients included 24 (27.6%) in the elderly group and 63 (73.4%)
in the younger group. Preoperative endocrinologic and radiologic assessments
showed no significant differences between the 2 groups. Although a grade 3
American Society of Anesthesiologists Physical Status classification was more
common in the elderly group (75% vs. 3%; P = 0.00001) owing to the severity of
associated diseases, no significant between-group difference in perioperative
complications was seen (17% vs. 6%; P = 0.142). Sixteen elderly patients and 45
younger patients achieved endocrinologic remission following surgery (67% vs.
71%; P = 0.426). The incidence rate of postoperative new pituitary deficit was
similar in the elderly and younger groups (4% vs. 3%; P = 0.625). Approximately
one-third of the elderly patients with diagnosed hypertension or diabetes
mellitus tapered their medication after successful tumor removal. CONCLUSIONS:
TTS can be considered a safe treatment for both younger and elderly patients with
acromegaly. Successful tumor removal provided a significant improvement in
comorbidities even in elderly patients with acromegaly.
PMID- 29966778
TI - Association of TGF-beta1 and WIF1 Expression with 36 Paired Primary/Recurrent
Nonfunctioning Pituitary Adenomas: A High-Throughput Tissue Microarrays
Immunohistochemical Study.
AB - OBJECTIVE: This study was undertaken primarily to research transforming growth
factor beta1 (TGF-beta1) and Wnt inhibitory factor 1 (WIF1) for the prediction of
nonfunctioning pituitary adenoma (NFPAs) invasion and recurrence of tumor samples
and the relations between quantitatively determined markers and clinical
characters. METHODS: We studied 104 patients, including 59 patients without
recurrence and 45 patients with recurrence (9 patients with one surgery and 36
patients operated twice, both tumors being studied). All tissues were
immunostained for TGF-beta1 and WIF1 using tissue microarrays and confirmed with
real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR)
and Western blot. RESULTS: We found that invasion, TGF-beta1, and WIF1 were
significantly associated with recurrence and that age was associated with low
expression of TGF-beta1 and WIF1 (P < 0.001). There were no statistically
significant differences in the expression of the 2 proteins between the
noninvasive and the invasive groups. The expression of TGF-beta1 and WIF1 in
primary tumors in the recurrence group was lower than in the nonrecurrence group
(P < 0.001). In the 36 paired primary or recurrent tumors, the expression of TGF
beta1 and WIF1 in recurrent tumors was higher than the expression of primary
tumors, which was confirmed with qRT-PCR and Western blot. Therefore, TGF-beta1
and WIF1 seem to be related to recurrence or progression of pituitary adenomas.
CONCLUSIONS: The expression of TGF-beta1 and WIF1 in NFPAs correlated with cell
proliferation and recurrence potential. They may be good markers of progressive
behavior in NFPAs; however, the biologic mechanism needs further study.
PMID- 29966779
TI - Delayed Intracerebral Hemorrhage After Pseudoaneurysm of Middle Meningeal Artery
Rupture: Case Report, Literature Review, and Forensic Issues.
AB - BACKGROUND: Traumatic pseudoaneurysm of the middle meningeal artery (PMMA) is
rare. Its rupture is associated with high mortality, so an early diagnosis is
recommended for this risky condition. In the absence of a specific guideline,
computed tomography (CT), digital subtraction angiography, and CT angiography
(CTA) are proposed for its diagnosis. CTA is the technique of choice even if it
is almost never performed, especially in mild head injury. We report a rare case
of a delayed rupture of PMMA, analyzed from a forensic point of view. METHODS:
Fifteen days after mild blunt head trauma, characterized by temporal fracture and
a small hemorrhage near the rim, a wide intraparenchymal hemorrhage (IPH)
occurred. The onset of IPH was marked by neurologic deterioration and arm
paralysis. Immediate head CT showed IPH, and CTA showed PMMA. Prompt surgery
could not help patient survival. The goal of autopsy was to formulate the cause
of death and to individuate potential medical negligence. RESULTS: In the
literature, 16 cases of 54 are related to PMMA (26%) and are associated with IPH.
IPH can be acute or delayed. Eight cases of acute IPH and 8 cases of delayed IPH
(including our case), both coexisting with PMMA, are described. The literature
review showed that the association of temporal rim fracture and a small
hemorrhage nearby is highly predictive of PMMA formation. CONCLUSIONS: Therefore,
in the presence of these 2 risk factors after heat trauma, CTA is strongly
suggested.
PMID- 29966780
TI - Unfavorable Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage WFNS
Grade I.
AB - BACKGROUND: Patients with an aneurysmal subarachnoid hemorrhage (aSAH) and World
Federation of Neurosurgical Societies (WFNS) grade I on admission are generally
considered to have a good clinical outcome. OBJECTIVE: The objective of this
study was to assess the actual clinical outcome of WFNS grade I aSAH patients,
and to determine which factors are associated with unfavourable outcome. METHODS:
For this prospective cohort study, 132 consecutive patients (age 18 years or
older) with a WFNS grade I aSAH admitted to our hospital between December 2011
and January 2016 were eligible. Clinical outcome was measured using the modified
Rankin Scale (mRS) at 6-month follow-up. Unfavorable outcome was defined as an
mRS score of 3-6. Univariable analyses were performed using logistic regression
models. RESULTS: Of 116 patients, only 5 patients (4%) had an mRS score of 0 and
most (65%) had an mRS score of 2. Twenty-five patients (22%) had an unfavorable
outcome. Nine (8%) patients died, of whom 4 died during admission. Factors
associated with unfavorable outcome were age (per increasing decade: odds ratio
[OR]. 1.78; 95% confidence interval [CI], 1.16-2.72), delayed cerebral ischemia
(OR, 4.32; 95% CI, 1.63-11.44), pneumonia (OR, 10.75; 95% CI, 1.94-59.46) and
meningitis (OR, 28.47; 95% CI, 1.42-571.15). CONCLUSIONS: Despite their
neurologically optimal clinical condition on admission, 1 in 5 patients with WFNS
grade I aSAH has an unfavorable clinical outcome or is dead at 6-month follow-up.
Additional multivariable analysis in larger patient cohorts is necessary to
identify the extent to which preventable complications contribute to unfavorable
outcomes in these patients.
PMID- 29966781
TI - Transcallosal Anterior Interforniceal Approach for Removal of Superior Midbrain
Cavernous Malformations in Children: A Retrospective Series of 10 Cases in a
Single Center.
AB - BACKGROUND: Surgical treatment of brainstem cavernous malformations (CMs) remains
a great challenge for neurosurgeons. Several cases published in the literature
have addressed surgical approaches. However, no surgical approach has been
reported to provide better exposure for CMs located in the superior midbrain.
METHODS: We presented 10 cases of superior midbrain CMs in children treated in
Beijing Tiantan Hospital from 2002 to 2016. The most common presenting signs and
symptoms were hydrocephalus and cranial nerve deficit. We used the transcallosal
anterior interforniceal approach in all patients to remove the CM lesion.
RESULTS: Total resection was achieved in all patients. During the follow-up
period, temporary short-term memory impairment was present in 5 patients,
unilateral ptosis occurred in 1 patient, and upward gaze dysfunction occurred in
2 patients. There was complete neurologic functional improvement for cranial
nerves. Exacerbation of hydrocephalus occurred in 4 patients requiring additional
ventriculoperitoneal shunt postoperatively. CONCLUSIONS: The transcallosal
anterior interforniceal approach can provide good exposure and direct
visualization to superior midbrain CMs. Complications are short-term and
reversible.
PMID- 29966782
TI - Subependymal Giant Cell Astrocytoma: A Surveillance, Epidemiology, and End
Results Program-Based Analysis from 2004 to 2013.
AB - BACKGROUND: Subependymal giant cell astrocytoma (SEGA) is a rare, benign neoplasm
predominantly associated with tuberous sclerosis complex. Clinical outcomes have
largely been conveyed via small- and medium-sized case series. METHODS: With the
Surveillance, Epidemiology, and End Results Program (SEER)-18 registry database,
information from all patients diagnosed with SEGA from 2004 to 2013 was obtained
(age, sex, race, marital status, tumor size, tumor location, occurrence of
surgery, receipt of radiation, and follow-up data). Age-adjusted incidence rates
and overall survival (OS) were determined. Cox proportional hazards model was
used for both univariate and multivariate analyses. RESULTS: The overall
incidence of SEGA within the SEER-18 database is 0.027 per 100,000 person-years
(95% confidence interval, 0.024-0.031). A total of 226 cases were identified. For
OS, univariate analysis revealed age younger than 18 years (hazard ratio [HR],
0.214; P = 0.004) and occurrence of surgery (HR, 0.328; P = 0.039) were
significant positive prognostic factors. Sex, marital status, race, tumor size,
tumor location, and receipt of radiation did not exhibit significant
relationships. Interestingly, subanalysis for extent of resection to gross total
resection did not show benefit. Multivariate analysis revealed that both age
younger than 18 years (HR, 0.193; P = 0.002) and occurrence of surgery (HR,
0.286; P = 0.021) remained significant. CONCLUSIONS: Based on our analysis,
younger age and occurrence of surgery are significant independent factors
associated with better OS. There was no support for radiation.
PMID- 29966783
TI - Drivers of Cost in Adult Thoracolumbar Spine Deformity Surgery.
AB - BACKGROUND: In an era of rising health care costs, it is prudent to consider
effective use of resources. Given the rapidly expanding elderly population with
an anticipated increase in adult spinal deformity, identifying the significant
cost drivers for the surgical management is an important step in the process of
increasing sustainability and cost-effectiveness of adult spinal deformity
surgery. METHODS: A total of 129 patients undergoing elective spine surgery for
thoraco-lumbar deformity were enrolled in a prospective longitudinal registry.
Patient-reported resource use during the 3-month postoperative period, including
outpatient visits, spine-related diagnostic tests, injections, emergency
department room visits, rehabilitation/skilled nursing facility utilization, and
use of all medications, was collected in a single-center prospective registry.
Multiple linear regression analysis was conducted to find the significant patient
coefficient for the cost variability. RESULTS: The study population showed
significant improvement (P < 0.001) in all patient-reported outcomes including
disability (Oswestry Disability Index), pain (Numeric Rating Scale for Back Pain
and Numeric Rating Scale for Leg Pain), and quality of life (Euro-Qol-5D). In
risk-adjusted multiple patient comorbidities including chronic obstructive
pulmonary disease and diabetes, preoperative deformity diagnosis, number of
levels involved, length of surgery and hospital stay, 90-day readmission and use
of inpatient rehabilitation were the significant drivers of the cost.
CONCLUSIONS: Our study demonstrates that several patient-specific, surgery
related factors, 90-day readmission and postdischarge inpatient rehabilitation
use, were associated with increased cost associated with the adult deformity
spine surgery.
PMID- 29966784
TI - Value of Diffusion-Weighted Imaging in the Diagnosis of Postoperative
Intracranial Infections.
AB - BACKGROUND: Magnetic resonance imaging (MRI), including diffusion-weighted
imaging (DWI), is an excellent tool for diagnosing intracranial infection, with
limitations in previous neurosurgical intervention. This study aimed to evaluate
the accuracy of DWI in the diagnosis of postoperative intracranial infection.
METHODS: We retrospectively evaluated all consecutive patients with intracranial
infection undergoing a neurosurgical intervention who had preoperative MRI,
including DWI. Patients were divided into 2 groups: spontaneous intracranial
infection (SI) and postoperative intracranial infection (PI). A control group
(CG) of patients who had undergone brain surgery without any signs of subsequent
infection was also included. Qualitatively, MRI data were evaluated for the
presence of intracranial infection. Sensitivity, specificity, and positive and
negative predictive values for PI as opposed to no infection were determined.
Quantitatively, areas with diffusion restriction within the surgery/abscess
cavity were identified for the 3 groups using semiautomated segmentation. Group
differences regarding apparent diffusion coefficient (ADC) ratios were evaluated.
Receiver operating characteristic curve analysis was used to identify a point in
time beyond which ADC ratios might show reasonable discriminatory power between
the PI and CG groups. RESULTS: A total of 78 patients were included (38 in the SI
group, 20 in the PI group, 20 in the CG group). Sensitivity, specificity, and
positive and negative predictive values in the diagnosis of PI were 80%, 95%, 4%,
and 100%, respectively. Median ADC was significantly higher in the PI group
compared with the SI group (0.98 vs. 0.69; P < 0.001) but lower compared with the
CG group (1.24; P = 0.16). The analysis suggested a possible differentiation of
PI and CG after a time interval of approximately 100 days/3 months. CONCLUSIONS:
DWI is of limited value in evaluating postoperative brain infection. Our data
show a trend toward DWI regaining its validity at approximately 3 months after
surgery.
PMID- 29966786
TI - Multiple Extradural Spinal Meningiomas in a Patient with Acquired
Immunodeficiency Syndrome: Case Report and Literature Review.
AB - BACKGROUND: Purely extradural spinal meningiomas are uncommon. Due to their
typical location in the neural foramen, they are often mistaken for schwannomas,
neurofibromas, and epidural metastases. In addition, comorbid conditions such as
immunodeficiency may obscure the diagnosis. We present a case of extradural
spinal meningiomas in a patient with human immunodeficiency virus (HIV). This is
the first reported case of multiple extradural spinal meningiomas in 2 separate
regions of the spine. CASE DESCRIPTION: A 40-year-old male with a past medical
history of HIV and hepatitis B infection presented with a 2-month history of
progressive back pain radiating to the left flank and thigh. Magnetic resonance
imaging of the thoracic and lumbar spine with intravenous gadolinium contrast
revealed 2 extramedullary masses in the left neural foramina of T6 and L1. The
patient underwent laminectomy, which revealed that the 2 lesions were entirely
extradural. Both lesions were resected, and the histological diagnosis for both
lesions was meningioma, World Health Organization grade I. CONCLUSIONS: Our
experience with this 40-year-old male with AIDS who presented with radicular
symptoms due to multiple purely extradural meningiomas underscores the importance
of considering meningioma as a possible diagnosis in patients with tumors of the
neural foramina. In addition, a wide differential diagnosis should be made for
patients with spinal lesions and history of HIV, including illnesses that are
related to immunodeficiency and those that are not.
PMID- 29966785
TI - Endovascular Retrieval of Migrated Coil within the Distal Middle Cerebral Artery
Using Stentriever Device.
AB - BACKGROUND: Displacement of endovascular coils during endovascular embolization
of an intracranial aneurysm is a potentially life-threatening complication.
Several methods for coil retrieval have been described, including the use of
microsnares and microforceps retrieval devices. With the recent surge of
stentriever implementation in the treatment of ischemic stroke, some operators
are now using such devices in the retrieval of migrated coils. We present a case
of a balloon-assisted coil embolization of a communicating segment internal
carotid artery aneurysm, complicated by coil migration far distally into the
middle cerebral artery, which was retrieved successfully with a stentriever. To
the best of our knowledge, this is the furthest migration of a coil to be
successfully retrieved with a stentriever. We review conservative and invasive
management of displaced coils and the technical advantages of stentrievers over
retrieval devices. METHODS: The patient's medical records were retrospectively
reviewed, including clinical and radiographic information. This study received
institutional review board approval. RESULTS: The patient was treated with
balloon-assisted coil embolization of the internal carotid artery aneurysm. The
migrated coil was retrieved successfully using a novel application of a
stentriever. CONCLUSIONS: In certain situations, a stentriever does not mandate
complete ensnaring of the target to be retrieved and thus need not always be
deployed distal to a migrated coil mass to be successful. Due to the mechanical
advantage of strut-engagement, stentrievers can afford to be positioned in
relatively suboptimal positions, and this is especially useful in cases involving
tortuous and small distal vessels (<2 mm diameter).
PMID- 29966787
TI - Cognitive Sequelae of Unruptured and Ruptured Intracranial Aneurysms and their
Treatment: Modalities for Neuropsychological Assessment.
AB - BACKGROUND: Cognitive sequelae frequently follow subarachnoid hemorrhage (SAH)
and include deficits across multiple domains of executive function. This factor
affects overall functional outcomes negatively, especially in younger patients.
Several clinical correlates predict development and severity of cognitive
dysfunction after SAH. Hypothetical mechanisms of cognitive dysfunction in the
absence of radiographic lesion include cerebral hypoperfusion and blood breakdown
products, resulting in perturbed interneuronal communication and network
synchrony, excitotoxicity, and altered microRNA expression. METHODS: The PubMed
database was searched for articles discussing cognitive outcomes in patients with
unruptured and ruptured intracranial aneurysmal disease, sequelae of treatment,
and modalities for neuropsychologic testing. RESULTS: Treatment of unruptured
intracranial aneurysms, although capable of preventing SAH, comes with its own
set of complications and may also affect cognitive function. Neuropsychological
tests such as the Montreal Cognitive Assessment, Mini-Mental Status Examination,
and others have proved useful in evaluating cognitive decline. Studies using
functional neurologic imaging modalities have identified regions with altered
activation patterns during various cognitive tasks. The sum of research efforts
in this field has provided useful insights and an initial understanding of
cognitive dysfunction after aneurysm treatment and SAH that should prove useful
in guiding and rendering future investigations more fruitful. CONCLUSIONS:
Development of finer and more sensitive neuropsychological tests in evaluating
the different domains of cognitive function after aneurysm treatment and SAH in
general will be useful in accurately determining outcomes after ictus and
comparing efficacy of different therapeutic strategies.
PMID- 29966788
TI - Vagal Nerve Stimulator Lead Revision Using Needle-Tip Cautery: Case Series,
Literature Review, and Technical Note.
AB - BACKGROUND: Vagal nerve stimulators (VNs) have been in use in the United States
since the 1990s as a palliative treatment option for drug-resistant epilepsy.
Over time, the electrode coils wrapped around the vagus nerve become encapsulated
by extensive scar tissue, making complete electrode removal challenging. We
present a case series of lead revision surgeries with a unique way to remove the
scar tissue around the vagus nerve, demonstrating a technique for complete
electrode removal. METHODS: This was a case series of 9 consecutive patients who
underwent complete removal of an existing VNs electrode using needle tip
monopolar electrocautery. RESULTS: Complete removal of the entire VNs electrode
array was achieved in all patients with no permanent complications seen at
postoperative follow-up at 3 months. CONCLUSIONS: Complete VNs electrode array
removal can be safely achieved by using needle tip monopolar electrocautery.
PMID- 29966789
TI - Complications Predicting Perioperative Mortality in Patients Undergoing Elective
Craniotomy: A Population-Based Study.
AB - OBJECTIVE: The objective of this study was to assess the independent effect of
complications on 30-day mortality in 32,695 patients undergoing elective
craniotomy. METHODS: The American College of Surgeons National Surgical Quality
Improvement Program was queried for patients undergoing elective craniotomy from
2006 to 2015. Multivariate logistic regression was used to examine the effect of
complications on mortality independent of preoperative risk and other
postoperative complications. This effect was further assessed in risk-stratified
patient subgroups using the American College of Surgeons National Surgical
Quality Improvement Program Surgical Risk Calculator. RESULTS: Of 13
complications analyzed, the 5 most strongly associated with mortality independent
of preoperative risk factors were unplanned intubation (odds ratio [OR], 12.1;
95% confidence interval [CI], 9.5-15.4; P < 0.001), stroke (OR, 11.1; 95% CI, 8.3
14.9; P < 0.001), ventilator requirement >48 hours after surgery (OR, 9.9; 95%
CI, 7.9-12.6; P < 0.001), and renal failure (OR, 8.5; 95% CI, 4.4-16.2; P <
0.001). These same complications were also the 5 most associated with mortality
independent of other postoperative complications. They were also associated with
mortality across all risk-stratified patient subgroups. On the contrary, venous
thromboembolism (OR, 1.3; 95% CI, 0.98-1.7; P = 0.06), urinary tract infection
(OR, 1.1; 95% CI, 0.76-1.6; P = 0.61), unplanned reoperation (OR, 1.1; 95% CI,
0.83-1.4; P = 0.55), and surgical site infection (OR, 0.35; 95% CI, 0.18-0.71; P
= 0.004) showed no significant link with increased mortality independent of other
complications. CONCLUSIONS: Of 13 complications analyzed, myocardial infarction,
unplanned intubation, prolonged ventilator requirement, stroke, and renal failure
showed the strongest association with mortality independent of preoperative risk,
independent of other complications, and across all risk-stratified subgroups.
These findings help identify causes of perioperative mortality after elective
craniotomy. Dedicating additional resources toward preventing and treating these
complications postoperatively may help reduce rates of failure-to-rescue in the
neurosurgical population.
PMID- 29966790
TI - MRI Tractography Detecting Cranial Nerve Displacement in a Cystic Skull Base
Tumor.
AB - A 37-year-old man came to our neurosurgical department with a 2-month history of
a progressive invalidating balance disorder. Cerebral magnetic resonance imaging
found a T2-weighted hypersignal lesion of the right cerebellopontine angle that
severely compressed the brainstem, however the position of cranial nerves was not
clearly identified. The new MRI diffusion tool, tractography, allowed to
reconstruct the trajectory of cranial nerves that were displaced by the tumor. As
such, the acoustic facial bundle was severely flattened posteriorly and
superiorly, while the lower nerves were pushed inferiorly. Effective
neurosurgical decompression was performed and confirmed the position of cranial
nerves V-XII. The patient was discharged and returned home without any cranial
nerve deficit. This case illustrates how advances in imaging can now better
describe the anatomy surrounding brain tumors and make surgery safer to the
benefit of patients.
PMID- 29966791
TI - Rate of Craniotomy Fusion After Free Bone Flap.
AB - BACKGROUND: Craniotomy has been performed in neurologic surgery for over a
century. Replacement of free bone flaps in routine craniotomies is widely
practiced, however, the rate of fusion after free flap replacement is unknown.
OBJECTIVE: To assess timing and rate of fusion after routine craniotomies.
METHODS: A retrospective cohort study of 2200 patients who underwent craniotomies
from 2002 to 2005. Fusion rates and time to fusion were evaluated. When time to
fusion was taken into consideration, univariate and multivariate analyses of the
impact of clinical factors on fusion rate were also examined. RESULTS: Of 171
patients with postoperative computed tomography of over 2200 patients undergoing
craniotomy, 103 (60%) demonstrated solid fusion, 26 (15%) had probable fusion,
and 42 (25%) had not achieved fusion. There were no significant differences when
fusion was compared with demographics such as age, sex, body mass index, and
history of tobacco use. Radiation therapy had a significant impact on fusion:
those receiving radiation were less likely to achieve fusion (P = 0.0082). The
fusion rates at 12, 24, and 36 months after surgery were 15%, 41%, and 54%,
respectively. CONCLUSION: As expected, craniotomy fusion rates after free flap
replacement increased steadily over time. We were not able to demonstrate that
clinical factors such as age, sex, body mass index, diagnosis, fixation material,
and radiation had an impact on fusion rate when time to fusion was accounted for.
Patients receiving radiation, however, experienced fusion less frequently.
Because of the scarcity of previous studies in this area, this current study
serves as a platform for future studies on fusion rates after free flap
replacement.
PMID- 29966792
TI - Morphometric Analysis of the Nucleus Accumbens Using the Mulligan Staining
Method.
AB - BACKGROUND: There is a need to further anatomically describe the nucleus
accumbens (NA), as there is a growing neurosurgical interest in this locus but a
limited understanding of its structure. In this study, we evaluated quantitative
NA parameters and spatial relationships with adjacent structures found in the
telencephalon. METHODS: A total of 155 NA specimens from coronal sections and 3
NA specimens from transverse sections were stained using the Mulligan technique
as modified by Barnard et al. The distance from the NA to other structures was
then measured. RESULTS: The mean radius of the 155 NAs in the coronal sections
was 6.23 +/- 0.964 mm, averaging 8.99 +/- 2.02 mm from midline (coordinate x),
27.09 +/- 3.15 mm from the insula, 12.95 +/- 3.21 mm from the outer border of the
putamen, 10.52 +/- 2.66 mm from the upper border of the caudate, and 8.84 +/-
2.93 mm from the midline of the lateral ventricle. The mean distance from the NA
center of gravity to the middle of the intercommissural line parallel to the
midline (coordinate y) was 17.08 +/-3.61 mm, and the mean vertical distance from
the intercommissural line to the NA was 8.12 +/- 1.265 mm. CONCLUSIONS: We
obtained the stereotactic coordinates of (x, y, z) = (8, 17, -8) for the NA. From
this and other delineations of the described position of the NA, it is possible
to contribute to stereotactic surgical atlases, improving neurosurgical
interventions in this structure.
PMID- 29966793
TI - Excellent Outcomes of Large-Volume Epidural Blood Patch Using an Intravenous
Catheter in 15 Consecutive Cases with Cerebrospinal Fluid Leak.
AB - OBJECTIVE: The effects of large-volume epidural blood patch (EBP) remain unclear
in patients with cerebrospinal fluid (CSF) leak. We report excellent outcomes
from 15 consecutive CSF leak cases that underwent a large-volume EBP using an
intravenous catheter from a single lumbar entry point, together with outcomes
from 4 patients who underwent direct surgical closure or drip-and-rest therapy
during the same period. METHODS: Nineteen patients with idiopathic CSF leaks were
enrolled in this study since November 2011 (12 women; mean age, 43.3 +/- 14.0
years). Patient demographic data, radiologic findings, symptoms, administrated
therapies, complications, and clinical courses were investigated retrospectively.
RESULTS: Different types of headache were observed, including typical orthostatic
headache alone (n = 10), orthostatic headache with chronic subdural hematoma
(CSDH) (n = 3), and posture-unrelated headache accompanied with CSDH (n = 6).
Regarding treatments, in 1 case, direct surgical closure was performed. In 15
cases, large-volume EBPs were performed, and the volume of injected blood was
44.8 +/- 21.6 mL. The other 3 cases were treated by simple drip infusion
regardless of the drainage for CSDH. Out of 9 cases with accompanied CSDH,
recurrence of subdural hematoma was completely prevented by the application of an
EBP after drainage in 5 cases and without drainage in 3 cases, and by simple
intravenous drip-and-rest therapy after drainage in 1 case. Among 10 patients
suffering from typical orthostatic headache alone, symptoms disappeared
completely in 7 cases and were relieved in 3 cases. CONCLUSIONS: We demonstrate
here a perfect control of spinal CSF leaks with the administration of a large
volume EBP through an intravenous catheter.
PMID- 29966794
TI - Clivus Inflammatory Pseudotumor Associated with Immunoglobulin G4-Related
Disease.
AB - BACKGROUND: Immunoglobulin G4 (IgG4)-related disease is a more recently
recognized syndrome. It is characterized by increasing IgG4-positive plasma cells
and lymphocyte infiltration. Reports of intracranial pseudotumors associated with
IgG4-related disease are very rare. We report a rare case of clivus pseudotumor
associated with IgG4-related disease mimicking meningioma. CASE DESCRIPTION: A 50
year-old man presented with abducens paralysis of the right eye. Brain magnetic
resonance imaging revealed a uniformly enhanced mass located in the right upper
clivus area, and meningioma was highly suspected. The tumor was totally resected
via a retrosigmoid approach craniotomy, which achieved sufficient decompression
of the right abducens nerve. Postoperative pathology revealed IgG4-related
disease with IgG4 strongly positive on immunohistochemical staining. The patient
had no history of autoimmune disease. Postoperative laboratory data revealed no
elevation of either IgG (6.94 g/L) or IgG4 (0.131 g/L). Follow-up contrast MRI
showed the lesion had disappeared. CONCLUSIONS: Although several cases of
intrasellar hypophysitis have been reported, reports of intracranial pseudotumors
associated with IgG4-related disease are rare. Special attention is required when
the differential diagnosis includes meningioma. Preoperative diagnosis is very
important because inflammatory pseudotumors associated with IgG4-related disease
could be treated with steroid therapy, avoiding surgery.
PMID- 29966795
TI - Breaking Bad News to Patients with Intracranial Tumors: The Patients'
Perspective.
AB - OBJECTIVE: Bad news refers to information that subjectively impedes a patient's
future prospects. Patients with intracranial tumors potentially face numerous
pieces of bad news. This study assessed the patients' perspective regarding the
content of bad news, patients' preferences for the communication of bad news, and
clinical consequences of mismatch of patients' communication preferences.
METHODS: We included 42 patients with an intracranial tumor shortly after
neurosurgical tumor removal. Patients' preferences for communication of bad news
was assessed via the Measure of Patients' Preferences Scale. Various areas of
patients' psychosocial well-being were included (e.g., depression or quality of
life). RESULTS: At this early stage of the disease trajectory, patients with a
brain tumor had already received on average 2.2 (standard deviation, 1.38; range,
0-6) pieces of bad news. For most patients, these pieces included receiving the
initial diagnosis. Patients reported a multitude of communication preferences,
some highly specific for patients with brain tumors. On average, 30% of these
preferences were not matched with the physicians' behavior. Communication
mismatch was associated with lower patient satisfaction regarding information but
no other areas of psychosocial well-being. CONCLUSIONS: Communicating bad news to
the patient with a brain tumor in a way that is appreciated by the patient is a
complex and demanding endeavor for the treating physician. Meeting patients'
needs not only requires the skills regarding the communication of cancer-related
news but also accounting for the specific needs ascribable to the neurologic
features of the disease (e.g., regarding neuropsychological impairment or
neurosurgical treatment).
PMID- 29966796
TI - Brachytherapy in Spinal Tumors: A Systematic Review.
AB - BACKGROUND: Conventional external beam radiation and stereotactic radiosurgery
are common radiation techniques used to treat spinal tumors. Intraoperative
brachytherapy (BT) may serve as an alternative when other options have been
exhausted or as an adjunct in combination with other therapies. The objective of
this study was to systematically review the literature on BT use in spinal tumor
surgery. METHODS: PubMed and Embase databases were systematically queried for
literature reporting the use of BT in the surgical treatment of spinal tumors.
PRISMA guidelines were followed. A meta-analysis was performed. RESULTS: Of the
203 initial articles queried, 15 studies were included. Of the 370 total patients
described, 78% were treated for spine metastases. Indications for BT included
tumors refractory to previous treatments and inability to tolerate chemotherapy,
radiation, and/or open surgery. Seed placement was the most common method of
delivery (58%) compared with plaques (42%). BT was placed during an open
procedure in 52%, and of the remaining percutaneous procedures, 47% were combined
with cement augmentation. Tumor recurrence rates varied from 13% to 49%. Seven
studies reporting visual analog scale scores reported significant improvement in
pain control. CONCLUSIONS: BT was used to treat metastatic disease in patients
who failed previous therapies and could not tolerate open surgery or further
therapy. This review summarizes the major findings in the available literature
pertaining to patient background, indications, and outcomes. Spinal BT seems to
be a viable option for spine tumor treatment and should be made available at
treating centers.
PMID- 29966797
TI - Pros and Cons of Tentative Clipping in Intracranial Aneurysm Surgery: Review of
867 Direct Clippings in Single Institution.
AB - OBJECTIVE: In direct aneurysm surgery, tentative clipping is frequently applied
to facilitate aneurysm dissection. However, no systemic review on the pros and
cons of tentative clipping has been conducted. This study aimed to investigate
the efficacy and concerns of tentative clipping. METHODS: A total of 867 direct
clippings in 737 patients were performed to treat intracranial aneurysms between
1994 and 2015. We retrospectively investigated the frequency, purpose, location,
and adequacy of tentative clipping. RESULTS: Tentative clipping was performed in
149 of the 867 aneurysms that were clipped (17.2%). The purpose of tentative
clipping was to dissect an aneurysm in 141 (94.6%), separate the vessels from the
surface of a sac in 5 (3.4%), and prevent slipping of the final clip in 3 (2.0%)
cases. Further dissection revealed that tentative clipping completely excluded
the blood flow into the aneurysm in 126 (84.6%) of the 149 cases and incompletely
shut it out in 23 (15.4%) cases. Five (21.7%) of the 23 patients with incomplete
clipping had intraoperative aneurysm ruptures subsequently. CONCLUSIONS:
Tentative clipping facilitates dissection of the aneurysm sac from the
surrounding structure but can occasionally lead to intraoperative rupture. Before
applying tentative clips, surgeons should prepare for temporary clipping or
additional tentative clipping in case of a rupture.
PMID- 29966798
TI - Veins of the Cerebellopontine Angle and Specific Complications of Sacrifice, with
Special Emphasis on Microvascular Decompression Surgery. A Review.
AB - Good knowledge of the anatomy of veins is of crucial importance for the
functional surgery of cranial nerve (CN) disorders, especially microvascular
decompression for trigeminal neuralgia (TN), hemifacial spasm (HFS), and
vagoglossopharyngeal neuralgia (VGPN). Although controversial, veins may be
involved in neurovascular conflicts and may constitute dangerous obstacles to
access to the CNs. With the aim of estimating the implications of veins in those
diseases and evaluating the linked surgical difficulties, we carried out a review
of the literature from 2000 to the end of February 2018. For this review,
articles found on PubMed that gave enough precision about veins were retained (39
articles on TN, 38 on HFS, 8 on VGPN, and 26 on complications related to venous
sacrifices). Before this review, we described a simplified anatomic
classification of veins, amenable to easing the surgical approach to CNs. Access
to the trigeminal nerve, via the infratentorial-supracerebellar route, is almost
always affected by the superficial superior petrosal venous system, whereas
access to the facial and cochleovestibular complex as well as to the lower CNs,
through the infrafloccular trajectory, is almost always exempt of important
venous obstacles. Respective incidences of venous compression at the origin of
hyperactive CN syndromes are given. The percentages of a venous conflict alone
were calculated at 10.8% for TN, 0.1% for HFS, and 2.9% for VGPN. We review the
complications considered in relation with venous sacrifices. Precautions to
minimize these complications are given.
PMID- 29966799
TI - Scientific Advances and New Frontiers in Mesothelioma Therapeutics.
AB - Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises
from the mesothelial surface of the pleural and peritoneal cavities, the
pericardium, and rarely, the tunica vaginalis. The incidence of MPM is expected
to increase worldwide in the next two decades. However, even with the use of
multimodality treatment, MPM remains challenging to treat, with a 5-year survival
rate of less than 5%. The International Association for the Study of Lung Cancer
has gathered experts in different areas of mesothelioma research and management
to summarize the most significant scientific advances and new frontiers related
to mesothelioma therapeutics.
PMID- 29966800
TI - Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus
Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell
Lung Cancer.
AB - INTRODUCTION: The phase III randomized PROFILE 1014 study demonstrated
superiority of crizotinib to first-line chemotherapy in prolonging progression
free survival (PFS) in previously untreated patients with ALK receptor tyrosine
kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent
with that in the smaller subset of East Asian patients in PROFILE 1014. The
subsequent study reported here prospectively evaluated crizotinib in a larger
East Asian patient population. METHODS: In this open-label phase III study
(PROFILE 1029), patients were randomized 1:1 to receive orally administered
crizotinib 250 mg twice daily continuously (3-week cycles) or intravenously
administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or
carboplatin [at a dose to produce area under the concentration-time curve of 5-6
mg.min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by
independent radiology review was the primary end point. RESULTS: Crizotinib
significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]:
0.286-0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8
months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6
93.2%) with crizotinib versus 45.6% (95% CI: 35.8-55.7%) with chemotherapy (p <
0.001). The most common adverse events were increased transaminase levels,
diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and
anemia with chemotherapy. Significantly greater improvements from baseline in
patient-reported outcomes were seen in crizotinib-treated versus chemotherapy
treated patients. CONCLUSIONS: First-line crizotinib significantly improved PFS,
objective response rate, and patient-reported outcomes compared with standard
platinum-based chemotherapy in East Asian patients with ALK-positive advanced
NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of
crizotinib and chemotherapy were consistent with those previously published.
PMID- 29966801
TI - ALLiance for sEcondary PREvention after an acute coronary syndrome. The ALLEPRE
trial: A multicenter fully nurse-coordinated intensive intervention program.
PMID- 29966802
TI - The AUStralian MEDiterranean Diet Heart Trial (AUSMED Heart Trial): A randomized
clinical trial in secondary prevention of coronary heart disease in a multiethnic
Australian population: Study protocol.
AB - The Mediterranean diet was first characterized as a heart-protective diet in the
1960s. The significant cardioprotective effects of the Mediterranean diet in
comparison to the standard-care low-fat diet have been established in the primary
prevention of cardiovascular disease (CVD); however, there is insufficient
evidence in secondary prevention research to influence the current standard of
care. Opportunity exists to assess the Mediterranean diet as a therapeutic target
for secondary CVD prevention within Australia's ethnoculturally diverse
communities. The AUSMED Heart Trial is a multisite randomized controlled trial
that will evaluate the efficacy of the Mediterranean diet for secondary
prevention of CVD in the Australian health care setting. This trial aims to
evaluate the effect of a 6-month Mediterranean diet intervention (delivered by
dietitians) versus a "standard-care" low-fat diet in reducing the composite
incidence of cardiovascular events at 12 months and at trial end in participants
with documented evidence of a previous acute myocardial infarction at trial
entry. The quality of the diet at baseline and follow-up will be assessed using
comprehensive dietary questionnaires and diaries as well as relevant dietary
biomarkers (such as urinary polyphenols and erythrocyte fatty acids).
Cardiovascular risk markers, including novel measures of immune and inflammatory
status, endothelial function, vascular compliance, platelet activity, and body
composition, will be collected to explore possible mechanisms for treatment
effect. Cost-effectiveness will also be estimated to support policy translation.
We plan to recruit 1,032 participants (516 per arm) from cardiology clinics in
major Australian hospitals in Melbourne, Adelaide, and Brisbane.
PMID- 29966803
TI - Compulsory treatment of drug use in Southeast Asian countries.
AB - BACKGROUND: Several Southeast Asian countries have implemented compulsory drug
detention centres in which people who use or are suspected of using drugs, mainly
amphetamine-type stimulants, are confined without their consent and in most cases
without due process and clinical evaluation of their substance use disorder.
Given these facilities' lack of access to evidence-based drug dependence
treatment, and the human rights implications of peoples' arbitrary detention
under the pretext of "treatment", international organizations have called for
their closure. The aim of this study was to estimate recent numbers of compulsory
drug treatment centres and of people in these centres in the region. METHODS: We
conducted an analysis of cross-sectional governmental data collected from seven
countries in the region with compulsory drug detention centres, namely Cambodia,
China, Lao PDR, Malaysia, the Philippines, Thailand and Viet Nam. We computed
descriptive data provided by government representatives for the period between
2012 and 2014. RESULTS: The total number of people in compulsory detention
centres overall decreased by only 4% between 2012 and 2014. In 2014, over 450,000
people were detained in 948 facilities in the seven countries. While only two
countries decreased the number of compulsory detention centres, most countries
increased the number of people detained. CONCLUSIONS: In spite of international
calls for the closure of compulsory detention centres, the number of facilities
and detained people remained high in the seven countries included in the
analysis. These officially reported figures are concerning regarding access to
effective drug dependence treatment and given the potential for additional human
rights abuses within compulsory detention centers. Further concerted policy and
advocacy efforts should support transition of treatment for people with drug
dependence towards human rights-based and evidence-based drug dependence
treatment. Expansion of existing drug and HIV services in the community rather
than compulsory treatment modalities will effectively address the region's drug
and HIV burden.
PMID- 29966804
TI - Developing a patient-reported experience questionnaire with and for people who
use drugs: A community engagement process in Vancouver's Downtown Eastside.
AB - People who use drugs (PWUD) frequently have complex health care needs, yet face
multiple barriers to accessing services. Involving PWUD in health service design
and evaluation can enhance the quality of data collected and ensure policy and
practice improvements reflect the expressed needs of the population. However,
PWUD remain largely excluded from the evaluation of health services that directly
affect their lives, including development of patient-reported experience measures
(PREMS) that have gained prominence in health services research and clinical
practice. Detailed descriptions of PWUD participation in survey design are
notably absent in the literature. In this commentary, we present a case that
demonstrates how PWUD can contribute meaningfully to the development of
questionnaires that assess patient-reported health care experiences. We describe
the development, implementation and outcomes of a process to engage local drug
user organizations in the evaluation of a redesign and reorientation of health
service delivery in the Downtown Eastside (DTES) neighborhood of Vancouver,
Canada. Through this process, participants contributed critical elements to the
design of a patient-reported experience measure, including: (1) identifying unmet
service needs in the neighborhood; (2) identifying local barriers and
facilitators to care; (3) formulating questions on cultural safety; and (4)
improving structure, language and clarity of the questionnaire. We highlight
lessons learned from the process, reflecting on the strengths, challenges and
ethical considerations associated with community-based approaches to
questionnaire development. The workshop model presented here illustrates one
flexible and promising approach to enabling meaningful participation of PWUD in
questionnaire development.
PMID- 29966805
TI - Tuberculosis infection among cocaine crack users in Brazil.
AB - BACKGROUND: WHO recommends treatment for latent tuberculosis infection (LTBI) in
the homeless and people who use drugs (PWUD). The optimal test for LTBI screening
is uncertain. METHODS: A cross-sectional study was conducted among the homeless
and drug-rehabilitation clinic clients chronically using crack in Western Brazil.
Participants were interviewed and offered HIV testing plus tuberculin skin
testing (TST) and QuantiFeron(r)-Gold-in-Tube (QFT). We considered LTBI when
either TST or QFT were positive. Factors associated with LTBI were adjusted in a
multivariate model. RESULTS: Among 372 subjects with at least one valid test, 216
(58%) had LTBI. TST was not read in 18.4%; QFT was indeterminate in 2.5%. TST
detected 27 (26%) extra LTBI cases among 75 QFT-negative individuals. PWUD had
over three-fold odds for LTBI. TST was 4.5 times more likely to be positive in
BCG-vaccinated individuals. CONCLUSION: Given the high risk of progression to
disease in this population, the high rates of loss to TST reading and the
possibility of false-positive TST results from BCG vaccination, we endorse
current CDC recommendations to use QFT for LTBI screening among the homeless and
PWUD. However, because adding TST to a negative QFT increased LTBI detection
considerably, TST should be considered in QFT-negative individuals.
PMID- 29966806
TI - Profile, risk practices and needs of people who inject morphine sulfate: Results
from the ANRS-AERLI study.
AB - AIMS: In France, a non-negligible proportion of opioid-dependent individuals
inject morphine sulfate. Although it has not yet been officially approved as an
opioid substitution treatment (OST), some physicians can prescribe its use for
people in methadone or buprenorphine treatment failure. Longitudinal data from
the ANRS-AERLI study, which evaluated an educational intervention for safer
injection called AERLI, provided us the opportunity to better characterize the
profile, risk practices and needs of people who inject morphine sulfate (MSI),
through comparison with other injectors, and to identify correlates of HIV/HCV
risk practices in this group. METHODS: The national multisite ANRS-AERLI study
assessed the impact of AERLI offered in volunteer harm reduction (HR) centers
("with intervention") (n = 113) through comparison with standard HR centers
("without intervention") (n = 127). All participants were scheduled to be
followed up for 12 months and have 3 telephone interviews: at baseline, 6 months
and 12 months. We compared MSI (n = 79) with other opioid injectors (n = 161) and
then used a mixed logistic model to identify factors associated with HIV/HCV risk
practices among MSI. FINDINGS: Of the 240 eligible participants, 79 were regular
MSI. They were less likely to use cocaine, crack or buprenorphine and to receive
OST than other participants. Conversely, MSI were more likely to inject drugs
more than three times a day and to report HIV/HCV risk practices. Among MSI,
multivariate analysis showed that those receiving morphine sulfate as an OST were
less likely to report such practices than other participants (aOR [95%CI] = 0.11
[0.02-0.61]). CONCLUSION: Our results show that while MSI use fewer stimulants,
they have more HIV/HCV risk practices than other injectors. However, when MSI are
prescribed morphine sulfate as a treatment, these practices tend to decrease. Our
findings suggest the importance of increasing access to morphine sulfate as a new
OST in France.
PMID- 29966807
TI - Prevalence of sleep problems and sleep-related characteristics in preschool- and
school-aged children with cerebral palsy.
AB - OBJECTIVES: To determine, in preschool- and school-aged children with cerebral
palsy (CP): (i) the prevalence of sleep disorders, including disorders of
initiation and maintenance of sleep, and (ii) the association between child
characteristics and sleep disorders. METHODS: Children with CP aged 3-12 years
were recruited from neurology clinics and a provincial CP registry. Caregivers
completed the Sleep Disturbance Scale for Children (SDSC) and a questionnaire on
sleep-related characteristics. Children's medical information was collected from
the registry and hospital records. RESULTS: 150 children with CP (mean age +/-
standard deviation: 6.9 +/- 2.9 years) completed the study (66 preschool-and 84
school-aged children). An abnormal total score on the SDSC was found in 20.7% of
children (10.6% and 28.6% of preschool-and school-aged children, respectively).
Overall, 44.0% of children had one or more sleep disorder (24.2% and 59.5% in
preschool-and school-aged children, respectively), as determined by subscales of
the SDSC. The most common sleep problem, disorders of initiation and maintenance
of sleep, was found in 26.0% of children (18.2% of preschool- and 32.1% of school
aged children, respectively). Pain was the strongest predictor of having an
abnormal total score and disorders of initiation and maintenance of sleep, with
odds ratios (95% confidence intervals) of 6.5 (2.2-18.9) and 3.4 (1.3-9.3),
respectively, adjusted for age group and degree of motor impairment. CONCLUSIONS:
Sleep disorders are prevalent in children with CP, with higher frequencies in
school-aged as compared to preschool-aged children. Health care professionals
caring for this population should routinely inquire about sleep problems and
pain.
PMID- 29966808
TI - Relationship between sleep patterns, sleep problems, and childhood enuresis.
AB - OBJECTIVE: Sleep dysfunction has been speculated to be involved in the
pathological mechanism of nocturnal enuresis (NE). However, results obtained from
previous studies were conflicting. This study evaluated and compared the sleep
patterns and problems between children with and without nocturnal enuresis (NE)
across different age and gender groups in a large epidemiological study. METHODS:
A multi-center, cross-sectional, epidemiological study was carried out in which
21,439 primary school children (10,655 boys and 10,784 girls aged 5.1-12.9 years)
and their parents participated. Chinese versions of the Children's Sleep Habits
Questionnaire and the General Condition Questionnaire were used to identify
nocturnal enuresis, sociodemographic characteristics, sleep patterns, and sleep
problems in children. The sleep patterns and problems were compared between
children with and without NE while controlling for a number of confounding
factors in different age and gender groups. RESULTS: It was observed that
children with NE (especially boys aged 11-12 years with severe NE) slept for a
shorter period and were more likely to have sleep problems such as bedtime
resistance, sleep duration disorder, night awakening, sleep anxiety, sleep
disordered breathing, and daytime sleepiness than those without NE. Girls with NE
were more likely to suffer from other types of parasomnias. CONCLUSION: Children
with NE, especially older boys with severe NE, were more sleep compromised than
those without NE. Our findings warrant further research on the mechanism of NE
and may have clinical implications for the treatment of childhood sleep problems
and NE.
PMID- 29966809
TI - Hypersomnia due to injury of the lower ventral ascending reticular activating
system in a patient with intraventricular hemorrhage.
PMID- 29966810
TI - Prospective associations between sleep problems and subtypes of anxiety symptoms
among disaster-exposed adolescents.
AB - OBJECTIVE: This study aimed to investigate longitudinal relationships between
sleep problems and subtypes of anxiety symptoms among adolescent earthquake
survivors. METHODS: Participants were 1573 adolescents (male, 45.8%; mean age at
baseline 15.01 years, standard deviation (SD) = 1.26) in the Wenchuan Earthquake
Adolescent Health Cohort. The Pittsburgh Sleep Quality Index and the Screen for
Child Anxiety Related Emotional Disorders were used to assess participants' sleep
problems and anxiety symptoms four times during 2.5 years after the earthquake.
Anxiety symptoms included subtypes of panic disorder (PD), generalized anxiety
disorder (GAD), separation anxiety disorder (SeAD), social phobia (SP), school
phobia (ScP). Longitudinal lagged generalized estimating equations (GEE) models
were used to determine the prospective associations. RESULTS: Overall, there was
a bidirectional relationship between sleep problems and anxiety symptoms. For the
specific sleep problems and anxiety subtypes, short sleep duration predicted
symptoms of PD, GAD, and ScP, and was predicted by GAD; difficulty falling asleep
predicted GAD symptoms, whereas PD symptoms increased difficulty falling asleep;
poor sleep quality predicted ScP symptoms and was predicted by symptoms of GAD
and ScP; difficulty maintaining sleep was not associated with any subtype of
anxiety symptoms in any direction; SeAD and SP were not associated with any
specific sleep problems in any direction. CONCLUSION: While sleep problems and
anxiety symptoms are bidirectional, the associations vary by subtypes of sleep
problems and anxiety symptoms. The potential biological mechanisms for the
specific associations between dimensional sleep and anxiety symptoms and their
clinical implications should be further investigated.
PMID- 29966811
TI - Vigabatrin and high-dose prednisolone therapy for patients with West syndrome.
AB - OBJECTIVE: Hormonal therapy and vigabatrin are now accepted as the first-line or
standard therapies for West syndrome (WS). However, the superiority of these
drugs in terms of monotherapy or combination therapy is still in question. In
this study, we designed a treatment protocol for WS and prospectively assessed
the efficacy of these therapies in controlling spasms, stabilizing
electroencephalography (EEG), and allowing for developmental catch-up. METHODS:
In patients diagnosed with WS, vigabatrin was first administered alone for 2
weeks, and then prednisolone was administered in combination with vigabatrin if
patients did not respond to vigabatrin. The detailed drug administration protocol
was as follows: vigabatrin 50 mg/kg/day for 1 day, followed by vigabatrin 100
mg/kg/day for 3 days, vigabatrin 150 mg/kg/day if spasms were still present or
the burden of amplitudes and epileptiform discharges (BASED) score on EEG was >=3
on day 5; 40 mg/day of prednisolone was added if spasms were still present or the
BASED score was >=3 on day 14. The prednisolone dose was increased to 60 mg/day
if spasms were still present or the BASED score was >=3 on day 21. RESULTS: Sixty
six patients newly diagnosed with WS (median seizure onset age: 5.7 [IQR, 4.1
7.1] months, median age at diagnosis: 6.6 [IQR, 5.4-8.1] months, n = 40 [60.6%]
boys) were subjected to the vigabatrin and prednisolone therapy protocol. Of the
66 patients, 22 (33.3%) patients showed resolution of spasms and a BASED score of
<=2 after vigabatrin alone, and 26 (39.4%) patients showed resolution of spasms
and a BASED score of <=2 after a combination of vigabatrin and prednisolone, for
a total of 48 (72.7%) patients who were responsive to the protocol without
relapse for at least 7 months after WS diagnosis. The mental and psychomotor age
quotients were higher at the time of diagnosis and remained significantly higher
6 months after the diagnosis in responsive patients (p < 0.001). No serious
adverse reactions leading to discontinuation or reduction of drug doses were
observed. CONCLUSION: Using a treatment protocol involving vigabatrin and
prednisolone for WS, 72.7% of patients showed resolution of spasms and a BASED
score of <=2. This study also found that this drug administration protocol was
safe. However, further studies are warranted as this study describes results from
observational study with limited sample size.
PMID- 29966812
TI - Epilepsy in classic Rett syndrome: Course and characteristics in adult age.
AB - PURPOSE: Rett syndrome (RTT) is a neurodevelopmental disorder that almost
exclusively affects females. Epilepsy is a major clinical feature, but its long
term course in RTT has not been sufficiently explored. This study addresses the
development of the epilepsy in adults with RTT. METHODS: Available females
diagnosed with RTT in Norway were asked to participate. Parents/caregivers were
interviewed, the girls/women were examined and their medical records reviewed.
Participants were categorized according to age, epilepsy, seizure patterns and
mutation severity groups. RTT severity was assessed (epilepsy score excluded).
RESULTS: 70 females with classic RTT were included. A presumed pathogenic
mutation in MECP2 was found in 96%. The presence of active epilepsy (seizures
last five years) was similar in all age groups above the age of ten: 11 (65%) in
adolescents (11-20 years), 9 (60%) in young adults (21-30 years) and 14 (67%) in
participants above 30 years of age. Tonic-clonic seizures within the last year
were present in 55, 67 and 64%, and >= weekly seizures occurred in 27, 45 and 50%
in the respective age groups. Among participants with active epilepsy, 69% had
unremitting seizures, whereas 31% had experienced remissions for more than six
months during the last five years. In the oldest group (>30 years), only 19% had
obtained seizure control for >5 years, and 14% had never experienced seizures.
Seizure activity correlated with RTT severity score, whereas the relationship to
mutation type remained ambiguous. CONCLUSION: Epilepsy continues to be a major
concern in adults with RTT. Two thirds of women above 30 years of age remained
with active epilepsy and 50% of them had seizures at least weekly.
PMID- 29966813
TI - The intensity of the inflammatory response in experimental porcine bruises
depends on time, anatomical location and sampling site.
AB - The assessment of the age of bruises inflicted on livestock is an important
component of veterinary forensic pathology investigations. However, the sampling
site within a bruise, the anatomical location and the mass and speed of the
object inflicting the blunt trauma might influence the intensity of the
inflammatory reaction. In the present study, the variation of the inflammatory
reaction within and along experimental porcine bruises was evaluated in order to
determine the optimal sampling site. Moreover, we evaluated if a combination of
histological characteristics and gene expression signatures was able to
differentiate bruises according to anatomical location, age of bruises and the
speed and mass of the object used to cause the impact. Twelve experimental
slaughter pigs were anesthetized, and on each animal four blunt traumas were
inflicted on the back using either a plastic tube or an iron bar, respectively.
The pigs were euthanized at 2, 5 or 8 h after infliction. Following gross
examination, skin and underlying muscle tissue were sampled from the center and
both ends of bruises and evaluated histologically. Subcutaneous fat tissue from
the center of the bruises was sampled for quantitative real-time polymerase chain
reaction to evaluate mRNA expression of 13 selected genes. Uninjured tissue was
sampled from the right thigh of all pigs and served as control tissue. The amount
of tissue damage and the intensity of the inflammatory reaction in bruises
depended on the sampling site within and along a bruise, the anatomical location
and the age of the bruise. The optimal site for sampling, i.e. the most
pronounced inflammatory reaction, was at the center of the bruises where the
plastic tube or iron bar first struck the skin. Moreover, bruises inflicted in
areas with a thin layer of subcutaneous fat tissue showed more damage and
inflammation in the underlying muscle tissue compared to bruises inflicted in
areas with a thicker layer of subcutaneous fat tissue. In addition, hemorrhage in
the muscle tissue was more likely present when bruises were inflicted with an
iron bar compared to a plastic tube. Combining histology and mRNA expression of
the 13 genes showed that the age of bruises could be determined with a precision
of +/-2.04 h. Moreover, the age of bruises could be determined with a precision
of +/-1.84 h based solely on mRNA expression of a selection of four genes.
PMID- 29966814
TI - Estimating age using permanent molars and third cervical vertebrae shape with a
novel semi-automated method.
AB - Estimating chronological age accurately in young adults is difficult and
additional methods are required to increase the accuracy. This study explored a
new semi-automated method to assess shape change of third cervical vertebra (C3)
with age in the living; comparing this as a method to determine whether
individuals could be categorised into being less than 18 years of age (<18), or
at least 18 years of age (>=18) with tooth formation of the second and third
mandibular molars (M2 and M3). The sample was panoramic and lateral skull
radiographs of 174 dental patients (78 males, 96 females aged 15-22 years).
Twelve variables were compared in two age categories: younger than 18 and at
least 18 years of age in males and females separately using a t-test. Tooth
formation of M2 and M3 was assessed. Mean values of eight variables of C3 in
males and one variable in females were significantly different between the two
age categories (p < 0.05). Results for males showed that the best age indicator
for age >=18 was the ratio between height and width of C3 and for females, the
ratio between diagonals. Results for molars showed that M2 was mature in 69% of
males and 83% of females, within the expected age range of 14-16 years. M3 was
highly variable ranging from stages 6-14 for both; M3 was missing in 24% of males
and 28% of females and mature in 14% of males and 15% of females. The conclusion
was that shape change of C3 has potential as an additional method to group
individuals <18 and >= 18 years of age.
PMID- 29966815
TI - Hearing and orally mimicking different acoustic-semantic categories of natural
sound engage distinct left hemisphere cortical regions.
AB - Oral mimicry is thought to represent an essential process for the
neurodevelopment of spoken language systems in infants, the evolution of language
in hominins, and a process that could possibly aid recovery in stroke patients.
Using functional magnetic resonance imaging (fMRI), we previously reported a
divergence of auditory cortical pathways mediating perception of specific
categories of natural sounds. However, it remained unclear if or how this
fundamental sensory organization by the brain might relate to motor output, such
as sound mimicry. Here, using fMRI, we revealed a dissociation of activated brain
regions preferential for hearing with the intent to imitate and the oral mimicry
of animal action sounds versus animal vocalizations as distinct acoustic-semantic
categories. This functional dissociation may reflect components of a rudimentary
cortical architecture that links systems for processing acoustic-semantic
universals of natural sound with motor-related systems mediating oral mimicry at
a category level. The observation of different brain regions involved in
different aspects of oral mimicry may inform targeted therapies for
rehabilitation of functional abilities after stroke.
PMID- 29966816
TI - A cluster randomized trial of community mobilization to reduce methamphetamine
use and HIV risk among youth in Thailand: Design, implementation and results.
AB - BACKGROUND: Use of methamphetamines (MA) and other stimulants have consistently
been associated with HIV/STI risk globally. We evaluated a community mobilization
intervention (Connect to Protect, C2P(r)) to prevent MA use among youth and
reduce HIV risk behaviors through community structural changes. DESIGN: A
community-randomized trial in northern Thailand with matched districts randomized
to C2P intervention or a standard voluntary counseling and testing (VCT) control.
Intervention districts formed stakeholders' coalitions to plan tailored local
prevention programs. Two independent random household samples of youth aged 14-24
were surveyed in 2009 and 2012. Lifetime and recent MA use was modeled with
multilevel logistic regression. RESULTS: Intervention initiatives included family
strengthening programs, school-based programs and opening a community drug
treatment center. Control communities applied the government-led "war on drugs"
approach in addition to youth and family programs. Baseline (N = 1077) and follow
up (N = 1225) samples included 47.5% females and 21.7% aged <=16. Lifetime MA use
in intervention districts reduced from 13.4% to 11.7% compared to reduction from
16.2% to 10.4% in the control districts (non-significant). In models, lifetime MA
use was associated with: time (aOR = 0.6, 95%CI: 0.38-0.83), females (aOR = 0.2,
95%CI: 0.15-0.29), increasing age (aOR = 2.4, 95%CI: 1.40-4.20, ages 16-19; aOR =
3.5, 95%CI: 2.00-6.12, ages >=20), and not being full-time students (aOR = 5.3,
95%CI: 3.77-7.37). Recent MA use showed similar results. Additionally, lifetime
MA use was significantly associated with alcohol use, risky sexual behaviors and
elevated depressive symptoms. CONCLUSIONS: Delay in developing and implementing
specific prevention programs in the intervention districts slowed diffusion of
the effect into the communities. Secular trends with contentious civil unrest and
active drug-enforcement efforts in the control communities also contributed to
the null intervention effect. Longer time and intensified efforts stressing a
public health approach are needed to demonstrate the effectiveness of community
mobilization in reducing substance use and HIV risk in this rural Thai community.
PMID- 29966817
TI - Can external interventions crowd in intrinsic motivation? A cluster randomised
field experiment on mandatory accreditation of general practice in Denmark.
AB - Motivation crowding studies have demonstrated that external interventions can
harm effort and performance through crowding out of intrinsic motivation, when
interventions are perceived as lack of trust. However, motivation crowding theory
also presents a much less investigated crowding in effect, which occurs when
external interventions increase intrinsic motivation. This study empirically
tests the motivational effect of a specific external intervention and its
associations with the perception of the intervention. We draw on a cluster
randomised stepwise introduction of a mandatory accreditation system in general
practice in Denmark combined with baseline and follow-up questionnaires of 1146
GPs. Based on a series of mixed effects multilevel models, we find no evidence of
motivation crowding out among surveyed GPs, although most GPs perceived
accreditation as a tool for external control prior to its implementation. Rather,
our results indicate that being accredited crowds in intrinsic motivation. This
is especially the case when GPs perceive accreditation as an instrument for
quality improvement. External interventions can therefore, at least in some
cases, foster intrinsic motivation of health care professionals.
PMID- 29966819
TI - The influence of affective behavior on impression formation in interactions
between black cancer patients and their oncologists.
AB - OBJECTIVE: Black patients and their physicians tend to form relatively negative
impressions of each other, and these may contribute to racial disparities in
health outcomes. The current research tested the hypothesis that the interaction
between positive and negative affective behavior predicts the most positive
impressions in clinic visits between Black patients and their oncologists.
METHOD: Naive coders rated patients' and oncologists' positive and negative
affective behavior in thin slices from 74 video recorded clinic visits. We
examined whether (a) physician positive affect, negative affect, or their
interaction predicted patients' perceptions of patient-centeredness,
trustworthiness, and confidence in recommended treatments and (b) patient
positive affect, negative affect, or their interaction predicted physicians'
perceptions of patient cognitive ability, likelihood of treatment adherence, and
likelihood of treatment tolerance. We also tested whether affective behavior
mediated relationships between race-related attitudes and post-visit impressions
or influenced post-visit impressions independently of attitudes. RESULTS: When
oncologists displayed relatively high levels of both positive and negative
affect, patients were more confident in recommended treatments but did not rate
physicians higher in patient centeredness or trustworthiness. When patients
expressed relatively high levels of positive and negative affect, oncologists
perceived patients to be higher in cognitive ability and more likely to adhere to
treatment recommendations, but no more likely to tolerate treatments. Affective
behavior influenced impressions independently of race-related attitudes.
CONCLUSIONS: Positive and negative affective behaviors jointly contribute to
impression formation in clinic visits between Black patients and oncologists, and
may have implications for patient treatment and outcomes in this underserved
patient population.
PMID- 29966818
TI - Social representations of mother-to-child transmission of HIV and its prevention
in narratives by young Africans from five countries, 1997-2014: Implications for
communication.
AB - International recommendations related to the prevention of mother-to-child
transmission (PMTCT) of HIV have evolved rapidly over time; recommendations have
also varied contextually in line with local constraints and national policies.
This study examines how young Africans made sense of mother-to-child transmission
(MTCT) and PMTCT and related barriers and facilitators between 1997 and 2014 in
the context of these complex and changing recommendations. It uses a distinctive
data source: 1343 creative narratives submitted to HIV-themed scriptwriting
competitions by young people aged 10-24 from 5 African countries (Senegal,
Burkina Faso, Nigeria, Kenya, and Swaziland) between 1997 and 2014. The study
triangulates between analysis of quantifiable characteristics of the narratives,
thematic qualitative analysis, and narrative-based approaches. MTCT occurs in 8%
of the narratives (108), while it is prevented in 5% (65). Narratives differ
according to whether they depict MTCT or PMTCT (or, rarely, both), evolve over
time, and show cross-national thematic variation. In the aggregate,
representations shift in line with increased access to testing and antiretroviral
medications, with PMTCT narratives becoming more frequent and MTCT narratives
becoming more hopeful as diagnosis becomes the gateway to ART access. However,
storylines of intergenerational tragedy in which MTCT is depicted as inevitable
persist through 2014. Alongside cross-national differences in theme and tone,
narratives from higher prevalence Swaziland and Kenya situate MTCT/PMTCT more
centrally within descriptions of life with HIV. Findings illustrate the need to
improve communication about PMTCT, reframing negative cultural narratives to
reflect the full promise of developments of the past decade and a half.
PMID- 29966820
TI - Longitudinal associations between work-family conflict and enrichment, inter
parental conflict, and child internalizing and externalizing problems.
AB - RATIONALE: Work-family conflict and enrichment refer to parents' challenges and
benefits of combining work and family roles. Emerging evidence suggests
detrimental effects of work-family conflict and facilitating effects of work
family enrichment on couple, family, and child functioning. This effect may be
more pronounced in mothers, who must juggle different roles within the family and
work context. To date, research has examined these relations as unidirectional,
but reciprocal associations may be possible. OBJECTIVE: This study investigated
the shape and direction of associations between maternal work-family conflict and
enrichment, child internalizing and externalizing problems, and inter-parental
conflict. METHOD: Growth curve modelling used six waves of biennial data spanning
ten years of childhood (4-5 to 14-15 years) for 2946 children and their employed
mothers from the Longitudinal Study of Australian Children. RESULTS: Results
indicated bidirectional associations between the work-family interface and child
outcomes; mothers' initial work-family conflict was associated with a quadratic
increase in child internalizing (but not externalizing) problems over time. Child
internalizing problems at 4-5 years predicted a linear decrease in mothers' work
family enrichment over time. However, work-family enrichment at 4-5 years was not
associated with the change in either child internalizing or externalizing
problems. Work-family conflict and inter-parental conflict at 4-5 years were not
associated with change in one another. Initial work-family enrichment was
associated with a quadratic decrease in inter-parental conflict, and initial
inter-parental conflict was associated with a linear increase in externalizing
problems; no evident reverse association was found. CONCLUSION: Findings
demonstrate the importance of the work-family interface in shaping family health
outcomes. The primary direction of influence was from work-family factors to
inter-parental conflict and child mental health problems. Thus, interventions
aimed at promoting family-friendly work environments and policies would likely
yield benefits for parents and their families.
PMID- 29966821
TI - The effect of mobility on HIV-related healthcare access and use for female sex
workers: A systematic review.
AB - Female sex workers (FSW) experience a high HIV burden and are often mobile. FSW
access to HIV-related healthcare is essential for equitable welfare and to reduce
new HIV infections. We systematically reviewed the literature on mobility and HIV
related healthcare access and use among FSW. Outcome measures included: HIV/STI
testing, STI treatment, PrEP (initiation or adherence), and ART (initiation or
adherence). We summarised the results with a narrative synthesis. From 7417 non
duplicated citations, nine studies from Canada (3), Guatamala, Honduras (2),
India, South Africa, and Vietnam were included. Only one of the studies was
designed to address mobility and healthcare access, and only six reported
adjusted effect estimates. Mobility was measured over four time-frames (from
'current' to 'ever'), as having lived or worked elsewhere or in another
town/province/country. Three studies from Canada, Guatemala, and India found
mobility associated with increased odds of poor initial access to healthcare
(adjusted odds ratios (AOR) from 1.33, 95% CI 1.02, 1.75, to 2.27, 95% CI 1.09,
4.76), and one from Vietnam found no association (odds ratio (OR): 0.92, 95% CI
0.65, 1.28). The study from South Africa found no association with initiating ART
(risk ratio: 0.86, 95% CI 0.65, 1.14). Two studies from Canada and Honduras found
increased odds of ART interruption (AOR 2.74, 95% CI 0.89, 8.42; 5.19, 95% CI
1.38, 19.56), while two other studies from Canada and Honduras found no
association with detectable viral load (OR 0.84, 95% CI 0.08, 8.33; AOR 0.79, 95%
CI 0.41, 1.69). We found that mobility is associated with reduced initial
healthcare access and interruption of ART, consistent with literature from the
general population. Discordance between effects on adherence and viral load may
be due to measurement of mobility. Future research should carefully construct
measures of mobility and consider a range of HIV-related healthcare outcomes.
PMID- 29966822
TI - Knowing less but presuming more: Dunning-Kruger effects and the endorsement of
anti-vaccine policy attitudes.
AB - OBJECTIVE: Although the benefits of vaccines are widely recognized by medical
experts, public opinion about vaccination policies is mixed. We analyze public
opinion about vaccination policies to assess whether Dunning-Kruger effects can
help to explain anti-vaccination policy attitudes. RATIONALE: People low in
autism awareness - that is, the knowledge of basic facts and dismissal of
misinformation about autism - should be the most likely to think that they are
better informed than medical experts about the causes of autism (a Dunning-Kruger
effect). This "overconfidence" should be associated with decreased support for
mandatory vaccination policies and skepticism about the role that medical
professionals play in the policymaking process. METHOD: In an original survey of
U.S. adults (N = 1310), we modeled self-reported overconfidence as a function of
responses to a knowledge test about the causes of autism, and the endorsement of
misinformation about a link between vaccines and autism. We then modeled anti
vaccination policy support and attitudes toward the role that experts play in the
policymaking process as a function of overconfidence and the autism awareness
indicators while controlling for potential confounding factors. RESULTS: More
than a third of respondents in our sample thought that they knew as much or more
than doctors (36%) and scientists (34%) about the causes of autism. Our analysis
indicates that this overconfidence is highest among those with low levels of
knowledge about the causes of autism and those with high levels of misinformation
endorsement. Further, our results suggest that this overconfidence is associated
with opposition to mandatory vaccination policy. Overconfidence is also
associated with increased support for the role that non-experts (e.g.,
celebrities) play in the policymaking process. CONCLUSION: Dunning-Kruger effects
can help to explain public opposition to vaccination policies and should be
carefully considered in future research on anti-vaccine policy attitudes.
PMID- 29966823
TI - Objectively-assessed neighbourhood destination accessibility and physical
activity in adults from 10 countries: An analysis of moderators and perceptions
as mediators.
AB - RATIONALE: Residents of neighbourhoods with high destination accessibility
(higher population density, more-interconnected streets, and better access to
services, public transport and parks) are more physically active. Evidence on the
factors that underlie these associations is sparse and inconsistent. OBJECTIVE:
We examined (1) five socio-demographic and four non-destination perceived
neighbourhood attributes as moderators of the relationship between objectively
assessed destination accessibility and moderate-to-vigorous physical activity
(MVPA); (2) perceived indicators of destination accessibility as mediators of
those relationships; and, (3) the generalizability of findings across 14 cities.
METHODS: Data were from the International Physical Activity and Environment
Network (IPEN) Adult study (N = 6822), which provided comparable objective and
perceived environmental variables and accelerometer-based MVPA from 14 cities
across 10 countries. Mediation and mediation moderation analyses were performed.
RESULTS: Objective net residential density, public transport density, and number
of parks in the neighbourhood were consistently associated with MVPA across all
examined socio-demographic groups and non-destination perceived neighbourhood
characteristics. However, only the association between number of parks and MVPA
was mediated by its conceptually-comparable perceived indicator. While the
associations of objective intersection density and land use mix with MVPA were
moderated by both gender and perceived pedestrian infrastructure/safety, only the
latter moderating effects were mediated by the conceptually-comparable perceived
indicators. Perceived neighbourhood safety and/or aesthetics moderated the
associations of objective ratio of retail/civic land to total area and distance
to nearest transport stop with MVPA. These associations were not mediated by the
conceptually-comparable perceived indicators. CONCLUSION: Densely populated
neighbourhoods with access to public transport and parks have the potential to
significantly and equitably contribute to adults' MVPA on a global scale.
Perceived neighbourhood aesthetics, pedestrian-friendliness and safety can
magnify the positive effects of mixed-use neighbourhoods on residents' MVPA by
interacting with the perceived ease of access to a variety of destinations.
PMID- 29966824
TI - Sex differences in the synergistic effect of prior binge drinking and traumatic
stress on subsequent ethanol intake and neurochemical responses in adult C57BL/6J
mice.
AB - Alcohol-use disorders (AUDs) are characterized by repeated episodes of binge
drinking. Based on reports that exposure to predator odor stress (PS)
consistently increases ethanol intake, the present studies examined whether prior
binge drinking differentially altered responsivity to PS and subsequent ethanol
intake in male and female mice, when compared to mice without prior binge
exposure. Initial studies in naive male and female C57BL/6J mice confirmed that
30-min exposure to dirty rat bedding significantly increased plasma
corticosterone (CORT) levels and anxiety-related behavior, justifying the use of
dirty rat bedding as PS in the subsequent drinking studies. Next, separate groups
of male and female C57BL/6J mice received seven binge ethanol sessions (binge) or
drank water (controls), followed by a 1-month period of abstinence. Then, 2
bottle choice ethanol intake (10% or 10E vs. water, 23 h/day) was measured in
lickometer chambers for 4 weeks. After baseline intake stabilized, exposure to
intermittent PS (2*/week * 2 weeks) significantly enhanced ethanol intake after
the 2nd PS in male, but not female, binge mice vs. baseline and vs. the increase
in controls. However, in a subgroup of females (with low baselines), PS produced
a similar increase in 10E intake in control and binge mice vs. baseline. Analysis
of lick behavior determined that the enhanced 10E intake in binge male mice and
in the female low baseline subgroup was associated with a significant increase in
10E bout frequency and 10E licks throughout the circadian dark phase. Thus, PS
significantly increased 10E intake and had a synergistic interaction with prior
binge drinking in males, whereas PS produced a similar significant increase in
10E intake in the low baseline subgroup of binge and control females. Plasma CORT
levels were increased significantly in both binge and control animals after PS.
CORT levels at 24-h withdrawal from daily 10E intake were highest in the groups
with elevated 10E licks (i.e., binge males and control females). At 24-h
withdrawal, protein levels of GABAA receptor alpha1 subunit, corticotropin
releasing factor receptor 1, and glucocorticoid receptor in prefrontal cortex
(PFC) and hippocampus (HC) were differentially altered in the male and female
mice vs. levels in separate groups of age-matched naive mice, with more changes
in HC than in PFC and in females than in males. Importantly, the sexually
divergent changes in protein levels in PFC and HC add to evidence for sex
differences in the neurochemical systems influenced by stress and binge drinking,
and argue for sex-specific pharmacological strategies to treat AUD.
PMID- 29966825
TI - Where are falls prevention resources allocated by hospitals and what do they
cost? A cross sectional survey using semi-structured interviews of key informants
at six Australian health services.
AB - BACKGROUND: Falls are a major problem for patients and hospitals, resulting in
death, disability and increased costs of healthcare. OBJECTIVES: This study aimed
to estimate the resource allocation across a partnership of large health
services, in an attempt to understand the amount and variability of resource
allocation to various falls prevention activities. DESIGN: A cross sectional
survey using semi-structured interviews. SETTING: Six tertiary health services in
Australia. PARTICIPANTS: A collaboration of six health services, spanning twenty
eight hospitals, was formed to investigate falls prevention resource allocation.
We interviewed 186 health service staff who were involved in falls prevention
activities, such as projects, audits and risk management, clinical and
operational managers responsible for falls prevention resource allocation and
clinical staff on targeted acute, subacute and mental health wards. METHODS: This
study used a mixed methods, cross sectional, observational design. To collect
data, we used key informant interviews with a purposive and snowball sampled
group of people working in the included health services. During interviews, study
participants were asked where and how falls prevention resources and equipment
were utilised and to estimate the time allocated to performing falls prevention
activities. The opportunity cost of each activity was estimated. All costs were
reported in Australian dollars. RESULTS: We estimate the annual opportunity cost
of health service attempts to prevent in-hospital falls across the six health
services to be AU$46,478,014. If we extrapolate this to a national level, health
services would be consuming AU$590 million per year in resources trying to
prevent falls in hospital. The areas of greatest resource consumption were
physiotherapy (18%), continuous patient observers (14%), falls assessments (12%)
and screens (8%), and falls prevention alarms (11%). Falls prevention alarms and
falls risk assessment screening tools were also used only for falls prevention,
and are potentially ineffective falls prevention strategies. CONCLUSIONS: Health
services are investing considerable amounts of resource in attempting to prevent
falls. However much of this resource is consumed in activities with weak or
little evidence of effectiveness. Health services may be better served by
considering tighter targeting, reduction or disinvestment in this area. This may
release time and resources which could be used to provide interventions with a
stronger evidence base, such as patient education using a structured patient
education program or in other areas of practice where evidence of benefit exist.
PMID- 29966826
TI - The work undertaken by mechanically ventilated patients in Intensive Care: A
qualitative meta-ethnography of survivors' experiences.
AB - BACKGROUND: Mechanical ventilation is a routine intervention for the critically
ill but patients' experiences of this intervention are largely hidden from
clinicians. A comprehensive understanding of Intensive Care Units survivors'
accounts is required to provide health professionals with evidence about the
patients' experience to deliver patient-centred care. OBJECTIVES: To synthesise
qualitative findings from international studies to understand Intensive Care Unit
survivors' experiences of mechanical ventilation, clarify the components of
patient-centred care from the patient perspective and understand what can be done
by health professionals to improve care processes. DESIGN: A meta-ethnography of
qualitative evidence following ENTREQ recommendations for reporting systematic
reviews. DATA SOURCES: Eight databases (MEDLINE, AMED, CINAHL, PsychINFO, Scopus,
WileyOnline, PubMed Central, TRIP) were systematically searched using a piloted
strategy described in a published protocol. Searches were completed on 31.8.16
and no date restrictions were placed. Searches were updated on 25.4.17. REVIEW
METHODS: Two researchers independently reviewed studies against pre-determined
inclusion criteria to assess their eligibility. Studies were included if they
reported on the adult patient experience of mechanical ventilation and used
qualitative data collection and analysis methods. All included studies were
quality appraised. Participant quotes and concepts, described within the
categories and themes of published studies, were extracted by one reviewer and
coded by two reviewers. A process of constant comparison, which is central to
meta-ethnography, facilitated the re-interpretation of data by a team of
researchers to generate the final qualitative synthesis. The Enhancing
Transparency in Reporting the Synthesis of Qualitative (ENTREQ) statement was
used to ensure that all synthesis stages were comprehensively reported. RESULTS:
Findings from 38 studies, with 608 participants, informed a patient-centred
trajectory model; three overlapping stages; alienation, hidden work and recovery
characterised the experiences of mechanical ventilation survivors. Health
professionals could positively influence the patient experience by promoting
'trust' and being vigilant so that patients felt 'safe'. Care provision that
promoted 'personalisation' helped participants to retain their identity as unique
human beings. CONCLUSIONS: For the first time the pooling of qualitative findings
from international studies, using meta-ethnography, has provided a patient
centred model of mechanical ventilation survivors' experiences of their care
processes. Patients may actively engage or passively endure the treatment burden
associated with mechanical ventilation.
PMID- 29966827
TI - Knowledge of, and participation in, advance care planning: A cross-sectional
study of acute and critical care nurses' perceptions.
AB - BACKGROUND: Nurses have a core role in facilitating discussions and enacting
decisions about end-of-life issues for patients in hospitals. Nurses' own
knowledge and attitudes may influence whether they engage in meaningful end-of
life conversations with patients. AIMS: To determine in a sample of nurses
working in acute and critical care hospital wards: 1) their knowledge of advance
care planning, including the authority of substitute decision-makers and legal
validity of advance directives; 2) their own participation in advance care
planning decision-making practices; and 3) associations between nurses' socio
demographic characteristics; clinical expertise; and knowledge and behaviour in
relation to advance care planning practices. DESIGN: Questionnaire-based, cross
sectional study. SETTING AND PARTICIPANTS: The study was conducted with 181
registered and enrolled nurses employed in acute and critical care wards of three
metropolitan hospitals in Australia. RESULTS: Nurses were least knowledgeable
about items relating to the authority of medical (56%) and financial (42%)
substitute decision-makers. Few nurses had prepared advance directives (10%) or
appointed medical (23%) or financial (27%) decision-makers, when compared to
discussing end-of-life wishes (53%) or organ donation (75%). Overall, 15% of
nurses had not engaged in any advance care planning practices. Nurses who had
cared for 11-30 dying patients in the last six months were more likely to have an
increased knowledge score. Older nurses were more likely to participate in a
greater number of advance care planning practices and an increase in shifts
worked per week led to a significant decrease in nurses' participation.
CONCLUSION: Nurses have a key role in providing advice and engaging dying
patients and their families in advance care planning practices. Nurses' own
knowledge and rates of participation are low. Further education and support is
needed to ensure that nurses have an accurate knowledge of advance care planning
practices, including how, when and with whom wishes should be discussed and can
be enacted.
PMID- 29966828
TI - Hospital nursing organizational factors, nursing care left undone, and nurse
burnout as predictors of patient safety: A structural equation modeling analysis.
AB - BACKGROUND: Promotion of patient safety is among the most important goals and
challenges of healthcare systems worldwide in countries including China.
Donabedian's Structure-Process-Outcome model implies that patient safety is
affected by hospital nursing organizational factors and nursing care process.
However, studies are imperative for a clear understanding about the mechanisms by
which patient safety is affected to guide practice. OBJECTIVE: The objective of
this study was to explore the impact of hospital nursing work environment,
workload, nursing care left undone, and nurse burnout on patient safety. DESIGN:
This was a cross-sectional study conducted in 23 hospitals in Guangdong province,
China in 2014. Data from nurses (n = 1542) responsible for direct care on 111
randomly sampled medical and surgical units were analyzed. METHODS: Work
environment was measured by the Practice Environment Scale of Nursing Work Index.
Workload was measured by day shift unit patient-nurse ratio and non-professional
tasks conducted by nurses. Nursing care left undone was measured by 12 items
addressing necessary nursing activities. Nurse burnout was measured by the
emotional exhaustion subscale of the Maslach Burnout Inventory-Human Services
Survey. Patient safety was measured by three items indicating nurses' perception
of overall patient safety and nine items addressing patient adverse events.
Structural equation modeling was used to examine a hypothesized model that
supposed work environment and workload have both direct and indirect effects on
patient safety through nursing care left undone and nurse burnout. RESULTS: The
findings generally supported the hypothesized model. Better work environment was
associated with better patient safety both directly and indirectly. Lower
workload primarily indirectly related to better patient safety. Nursing care left
undone and nurse burnout were mediators negatively associated with patient
safety. CONCLUSIONS: Improving work environment, increasing nurse staffing
levels, and providing sufficient support for nurses to spend more time on direct
patient care would be beneficial to patient safety improvement.
PMID- 29966829
TI - Radiologically isolated syndrome in children: Current knowledge and future
directions.
AB - As the use of magnetic resonance imaging (MRI) grows in clinical practice,
clinicians are increasingly faced with the difficult task of interpreting the
significance of incidental findings on brain MRI. Among individuals found to have
incidental brain MRI findings, a small number have white matter abnormalities on
MRI that resemble the demyelinating lesions of multiple sclerosis (MS) in the
absence of a history of relevant clinical symptoms. This has been termed
radiologically isolated syndrome (RIS). Recent years have seen growing interest
in RIS, with observational studies that have specifically focused on answering
questions regarding the subsequent risk of future clinical events and diagnosis
of MS in adults and children with these findings. Given the high rate of
subsequent clinical events seen in adult studies, knowledge related to RIS in
children is paramount, particularly given the higher disease activity and burden
in children with MS. This review examines this question, providing an overview of
RIS with a focus on its significance in children including current definitions,
its association with MS, and knowledge related to therapeutic interventions for
RIS. We conclude with suggestions for an approach to assessment of and subsequent
surveillance in children fulfilling criteria for RIS and directions for future
study.
PMID- 29966830
TI - Expression of vitamin D receptor in clear cell papillary renal cell carcinoma.
AB - Clear cell papillary renal cell carcinoma (ccpRCC) is a recently recognized
subtype of renal cell carcinoma. In this study, we investigated the
clinicopathological and immunohistochemical features in a group of 26 cases of
ccpRCC, with a special emphasis on the expression of vitamin D receptor (VDR).
The mean age of patients was 53.3 years (range 36-74 years), and the mean tumor
size was 2.5 cm (range 0.5 to 6.5 cm). During follow-up (range 12-121 months,
median 50 months), no recurrence or metastasis was observed. Histopathologically,
all cases of ccpRCC exhibited a tubular and papillary architecture, covered by
tumor cells with clear cytoplasm. Immunohistochemistry showed intermediate (5/26,
19%) to diffuse (21/26, 81%) and moderate (2/26, 8%) to strong (24/26, 92%)
membranous staining for VDR in each case. All cases (26/26, 100%) were diffuse
and strong cytoplasmic and fibrillar staining for cytokeratin 7 (CK7), but
negative foralpha-methylacyl-CoA-racemase (AMACR). Each case showed diffuse
(26/26, 100%) and moderate (4/26, 15%) to strong (22/26, 85%) membranous staining
for carbonic anhydrase IX (CA IX). In addition, the majority of cases showed
negative for cluster of differentiation 10 (CD10) (20/26, 77%) and renal cell
carcinoma maker (RCC-Ma) (24/26, 92%). This unique staining pattern is helpful
for distinguishing ccpRCC from its mimics. Furthermore, VDR positive expression
suggests that ccpRCC originates from the precursor epithelium of distal nephron.
PMID- 29966832
TI - New biomarkers of human papillomavirus infection in acute cervical
intraepithelial neoplasia.
AB - Acute human papillomavirus (HPV) infection of the cervix (cervical
intraepithelial neoplasia, CIN) is marked by high copy episomal viral DNA and
L1/L2 capsid protein expression (productive infection) in the cells towards the
surface that facilitate sexual viral transmission. Viral DNA is low copy and not
associated with viral capsid protein expression in the less differentiated lower
part of the CIN (nonproductive infection). The purpose of this study was to
examine the host response in these two areas. Serial section and co-localization
analyses demonstrated that in 29/33 (88%) of cases the NF-kappaB pathway was
activated and localized to the suprabasal nonproductively infected cells in the
CIN lesions. There was a concomitant increased expression of importin-beta,
exportin-5, Mcl1, p16, Ki67 and cFLIP in 32/33 (96%) of CIN lesions that likewise
localized primarily to the nonproductively infected cells. Only Ki67 and exportin
5 were expressed, though much less so, in the adjacent, normal squamous
epithelia. The viral proteins E1^E4 and L1 were localized to productively
infected cells whereas E6/E7 protein/RNA was rarely present in early CIN. It is
concluded that the host viral response to acute cervical HPV infection includes
strong increased expression of proteins besides p16 and Ki67. These include
importin-beta, exportin-5, Mcl1, and cFLIP in cells with low copy and relatively
quiescent viral DNA that, in turn, may serve as new biomarkers of this disease.
PMID- 29966831
TI - MiR-155 deletion reduces ischemia-induced paralysis in an aortic aneurysm repair
mouse model: Utility of immunohistochemistry and histopathology in understanding
etiology of spinal cord paralysis.
AB - Spinal cord paralysis is relatively common after surgical repair of thoraco
abdominal aortic aneurysm (TAAA) and its etiology is unknown. The present study
was designed to examine the histopathology of the disease and investigate whether
miR-155 ablation would reduce spinal cord ischemic damage and delayed hindlimb
paralysis induced by aortic cross-clamping (ACC) in our mouse model. The loss of
locomotor function in ACC-paralyzed mice correlated with the presence of
extensive gray matter damage and central cord edema, with minimal white matter
histopathology. qRTPCR and Western blotting showed that the spinal cords of wild
type ACC mice that escaped paralysis showed lower miR-155 expression and higher
levels of transcripts encoding Mfsd2a, which is implicated in the maintenance of
blood-brain barrier integrity. In situ based testing demonstrated that increased
miR-155 detection in neurons was highly correlated with the gray matter damage
and the loss of one of its targets, Mfsd2a, could serve as a good biomarker of
the endothelial cell damage. In vitro, we demonstrated that miR-155 targeted
Mfsd2a in endothelial cells and motoneurons and increased endothelial cell
permeability. Finally, miR-155 ablation slowed the progression of central cord
edema, and reduced the incidence of paralysis by 40%. In sum, the surgical
pathology findings clearly indicated that the epicenter of the ischemic-induced
paralysis was the gray matter and that endothelial cell damage correlated to
Mfsd2a loss is a good biomarker of the disease. MiR-155 targeting therefore
offers new therapeutic opportunity for edema caused by traumatic spinal cord
injury and diagnostic pathologists, by using immunohistochemistry, can clarify if
this mechanism also is important in other ischemic diseases of the CNS, including
stroke.
PMID- 29966833
TI - Non-neoplastic adrenal pseudocysts: A clinicopathologic study of 44 cases with
potential insights into pathogenesis.
AB - BACKGROUND: Literature on non-neoplastic adrenal pseudocysts (NNAPC) remains
limited and to date no large series have been reported. The pathogenesis of these
lesions remains poorly defined, however a vascular origin is most often suggested
in the literature. We aimed to evaluate the clinicopathological features and the
spectrum of vascular changes within NNAPC, in order to better understand the
mechanisms and circumstances of their pathogenesis. METHODS AND RESULTS: We
reviewed 44 cases of surgically resected NNAPC. There were 30 females and 14
males ranging from 23 to 82 years (median, 53 years). On the basis of
histopathologic and immunohistochemical analysis of the vascular changes the
following types were defined: pseudocysts with lymphatic-related changes (type 1,
n = 16), pseudocysts with large vein-related changes (type 2, n = 15) and
pseudocysts with blood vessel microvasculature-related changes (type 3, n = 13).
The median patient age of the latter group was higher than that of type 1 and 2
(64 years versus 51 and 50 years, respectively; p = 0.0002). Type 3 pseudocysts
were more frequently associated with a history of systemic vascular and vascular
related disorders than type 1 and type 2 pseudocysts (92% versus 33% and 64%,
respectively; p = 0.008). Type 1 pseudocysts were more frequently connected with
a history of previous intra-abdominal surgical procedures than type 2 and 3
pseudocysts (60% versus 7% and 25%, respectively; p = 0.0079). CONCLUSIONS: NNAPC
are clinically heterogenous and can arise on a background of various vascular
changes. They may represent end-stage processes related to lymphangiomatous
lesions, changes in adrenal venous structures or microvasculature.
PMID- 29966834
TI - OTA induces intestinal epithelial barrier dysfunction and tight junction
disruption in IPEC-J2 cells through ROS/Ca2+-mediated MLCK activation.
AB - Ochratoxin A (OTA) is a frequent contaminant of feed and food worldwide. The
toxicity of OTA on intestinal barrier was investigated in porcine intestinal
epithelial cells (IPEC-J2). We observed that OTA induced intestinal barrier
dysfunction as indicated by the reduction in transepithelial electrical
resistance (TEER) and elevation in paracellular permeability to 4 kDa dextran.
The barrier dysfunction was accompanied with tight junction disruption including
a down-regulation in ZO-1 expression and redistribution of Occludin and ZO-1.
Moreover, OTA exposure increased reactive oxygen species (ROS) generation,
elevated the intracellular calcium level ([Ca2+]c) and activated myosin light
chain kinase (MLCK). Simultaneously, NAC, a ROS scavenger, blocked OTA-induced
ROS generation, [Ca2+]c elevation, barrier dysfunction and tight junction
disruption, suggesting that OTA-induced ROS generation may act as a trigger.
Next, we found that OTA-induced MLCK activation was inhibited by BAPTA-AM, the
cytosolic Ca2+ chelator, demonstrating that OTA-induced MLCK activation is
dependent on [Ca2+]c elevation. Furthermore, inhibition of MLCK with ML-7 or
inhibition of [Ca2+]c elevation with BAPTA-AM markedly prevented OTA-induced
barrier dysfunction and tight junction disruption. Taken together, our results
indicated that OTA induces ROS generation, and then elevates the [Ca2+]c and MLCK
activity in turn, which finally induces barrier dysfunction and disrupts tight
junction in IPEC-J2 cell monolayers.
PMID- 29966835
TI - Cascading effects of elevated ozone on wheat rhizosphere microbial communities
depend on temperature and cultivar sensitivity.
AB - Tropospheric ozone (O3) concentrations have now reached levels that can
potentially affect crop production in several regions of the world. The
interacting effects of the elevated O3 and temperature on plants are still
unclear and their consequences on the rhizosphere microbial communities never
studied yet. Here, we conducted a 3-week fumigation experiment on two cultivars
of wheat with different tolerance to O3 (Premio and Soissons) at two temperatures
(20 degrees C and 30 degrees C). The impacts of O3 were measured on plants
physiology, rhizosphere chemical environment and microbial communities. Globally,
most of the results showed that elevated O3 effects were more pronounced at 20
degrees C than 30 degrees C, especially on the most O3-sensitive cultivar
(Soissons). Elevated O3 reduced significantly plant root biomass (up to -37% for
Soissons) compared to non-fumigated plants. A decrease in the dissolved organic
matter with a relative increase of aromatic compounds concentration was also
observed under elevated O3, suggesting quantitative and qualitative impacts on
roots exudation. While bacterial abundance was negatively affected by O3 plant
stress, fungal abundance was found to be stimulated (up to 12 fold compared to
non-fumigated plants for Soissons at 20 degrees C). These changes were
accompanied by modifications of the genetic structures and metabolic profiles,
with a relative increase of amino acids catabolism. This fully controlled
laboratory experiment showed that the effects of elevated O3 on soil microbial
communities i) are plant-mediated and depend on the cultivar sensitivity, ii)
decrease in warming condition, iii) increase the fungi to bacteria ratio and iv)
alter both the genetic structure and the metabolic activities. This study
highlights the importance of considering interactive effects between pollutants
and climate changes on plant-microbe relationship to better inform models and
improve predictions of future states of agroecosystems.
PMID- 29966836
TI - Silicon nutrition lowers cadmium content of wheat cultivars by regulating
transpiration rate and activity of antioxidant enzymes.
AB - Given that cadmium (Cd) uptake by plants is linked to transpiration rate and
activity of antioxidant enzymes and further that silicon (Si) can regulate them,
it was hypothesized that improved Si nutrition could reduce Cd concentration in
plants. Thus, present study was carried out to elucidate the positive effect of
Si nutrition on the growth, activities of antioxidant enzymes and tissue cadmium
(Cd) concentration in Cd-tolerant (Iqbal-2000) and Cd-sensitive wheat (Triticum
aestivum L.) cultivars. Fifteen days after seedling transplantation, 15 MUM Cd
stress alone and in combination with 0.6 mM Si was applied. Silicon application
improved root and shoot dry matter of Cd-sensitive cultivar Sehar-2006 while the
effect was non-significant in Cd-tolerant cultivar Iqbal-2000. Silicon-treated Cd
sensitive cultivar showed marked improvements in chlorophyll content and
photosynthesis, while stomatal conductance and transpiration rate decreased by Si
application. Silicon treatment enhanced the activities of enzymatic antioxidants
including catalase, ascorbate peroxidase, guaiacol peroxidase and superoxide
dismutase and the increase was higher for Cd-tolerant cultivar Iqbal-2000.
Although Si nutrition depressed malondialdehyde (MDA) content in both Cd-stressed
cultivars, the response was more evident in Cd-sensitive Sehar-2006. Lower lipid
peroxidation was related to Si-induced increase in antioxidant activities only in
Cd-sensitive cultivar. Silicon application decreased Cd accumulation in the roots
and shoots of both the cultivars. The decrease in shoot Cd was associated with a
decrease in Cd uptake by roots and Cd translocation from roots to shoots.
Overall, it is concluded that Si suppressed Cd contents by decreasing
transpiration rate in Cd-sensitive cultivar and by increasing antioxidant
activity in Cd-tolerant cultivar.
PMID- 29966837
TI - The prediction of combined toxicity of Cu-Ni for barley using an extended
concentration addition model.
AB - Environment pollution often occurs as an obvious combined effect involving two
(or more) elements, and this effect changes with the concentrations of the
different elements. The effects on barley root elongation were studied in
hydroponic systems to investigate the toxicity of Cu-Ni combined at low doses and
at a fixed concentration ratio. For low doses of Cu-Ni, the addition of Ni (<0.5
MUM) to Cu significantly decreased Cu toxicity for barley, but the addition of Cu
(<0.25 MUM) had no significant effect on Ni toxicity. At a fixed concentration
ratio, according to the single effective concentration (EC) (barley root
elongation inhibitory concentration) values of Cu and Ni, five sets of Cu-Ni
fixed ratios were used: ECn(Cu)+ECm(Ni) (n + m = 100) (ECn and ECm indicate
toxicity unit value for n% and m% inhibition of barley root length,
respectively). The calculated toxicity unit value for 50% inhibition of root
length ranged from 0.44 to 0.98 (i.e., <1), indicating a synergistic effect. To
consider the interactions between the metal ions, the extended concentration
addition model (e-CA) was established by integrating the Cu-Ni interaction into
the concentration addition model (CA), and the data of two groups (the low doses
of Cu-Ni and at a fixed concentration ratio) were respectively fitted. The e-CA
accurately predicted the root length of barley under the Cu-Ni combined action.
The correlation coefficient (r) and the root-mean-square error (RMSE) between
predicted and observed values were 0.97 and 6.6 (low-dose group) and 0.96 and
8.12 (fixed-ratio group), respectively, and e-CA significantly improved the
prediction accuracy compared to the traditional CA model without consideration of
the Cu-Ni competition (r = 0.89, RMSE = 14.16). The results provided a
theoretical basis for evaluation and remediation of soil contaminated with heavy
metal composites.
PMID- 29966839
TI - Irrelevance of accusations against Hermann Muller.
PMID- 29966838
TI - Seasonal and spatial variations in the occurrence, mass loadings and removal of
compounds of emerging concern in the Slovene aqueous environment and
environmental risk assessment.
AB - This study reports the development of a multi-residue method for determining 48
compounds of emerging concern (CEC) including three diclofenac transformation
products (TP) in Slovenian wastewater (WW) and surface water (SW). For solid
phase extraction (SPE), OasisTM Prime cartridges were favoured over Oasis HLBTM.
The validated method was then applied to 43 SW and 52 WW samples collected at
nine locations. Ten bisphenols in WW and 14 bisphenols in SW were traced in
Europe for the first time. Among all of the 48 targeted CEC, 21 were >LOQ in the
influents and 20 in the effluents. One diclofenac TP was also quantified in WWs
(3.04-78.1 ng L-1) for the first time. As expected, based on mass loads in the
wastewater treatment plant influents, caffeine is consumed in high amounts
(105,000 mg day-1 1000 inhab.-1) in Slovenia, while active pharmaceutical
ingredients (APIs) are consumed in lower amounts compared to other European
countries. Removal was lower in winter in the case of four bisphenols (17-78%),
one preservative (36%) and four APIs (-14-91%), but remained constant for
caffeine, one API, two UV-filters and three preservatives (all >85.5%). Overall,
a constructed wetland showed the lowest (0-80%) and most inconsistent removal
efficiencies (SD > 40% for some CECs) of CECs including caffeine, two UV-filters,
two preservatives and two APIs compared to other treatment technologies. The
method was also able to quantify Bisphenol S in SW (<36.2 ng L-1). Environmental
risk was assessed via risk quotients (RQs) based on WW and SW data. Two UV
filters (oxybenzone and dioxybenzone), estrone and triclosan, despite their low
abundance posed a medium to high environmental risk with RQs between 0.282 (for
HM-BP) and 15.5 (for E1).
PMID- 29966841
TI - Nonlinear elastic imaging of barely visible impact damage in composite structures
using a constructive nonlinear array sweep technique.
AB - Linear and nonlinear ultrasound imaging methods highlight different damage
features: the linear method detects large stiffness changes, while the nonlinear
technique identifies small impedance mismatches, such as microcracks or closed
delaminations. Typically, nonlinear ultrasound techniques detect damage/defects
in materials by measuring higher order harmonics. These harmonics can be
difficult to measure due to low magnitude and signal to noise ratios (SNR): hence
large excitation amplitudes are needed, which can further complicate the
reliability of these methods as equipment nonlinearities can be generated. To
overcome these issues, exciting at specific frequencies, known as local defect
resonances (LDR), produce a much larger displacements at the damaged regions.
However, estimation of LDR is time-consuming, complex and not an easily automated
process. A coupled baseline-free linear and nonlinear ultrasonic imaging approach
is proposed, using a Constructive Nonlinear Array Sweep excitation and an image
subtraction method for identifying damage in layered materials. The signal sweep
method uses a narrow band frequency excitation to increase the probability of
detection of a LDR frequency. The novel imaging approach was employed using laser
vibrometry measurements in various complex composite structures to assess barely
visible impact damage, critical for the aircraft industry. The results showed
better estimation of impact damage when compared to classical linear or nonlinear
ultrasonic methods leading to improved reliability of aircraft inspections.
PMID- 29966840
TI - Alterations in urinary metabolomic profiles due to lead exposure from a lead-acid
battery recycling site.
AB - Lead poisoning is considered a public health threat, particularly in developing
countries. Health problems from Pb exposure occur in many parts of the world,
especially near Pb mines, Pb smelters, and used lead-acid battery (ULAB)
recycling plants. In this study, we analyzed the urine metabolome of residents in
a village located near a ULAB recycling facility to investigate the biological
effects of Pb exposure (ULAB: n = 44, Reference: n = 51). Lasso linear regression
models were moderately predictive of blood Pb levels, as evaluated by a training
set (R2 = 0.813) and against an external test set (R2EXT = 0.647). In lasso
logistic regression models, areas under receiver operating characteristic curves,
as measured by 5-fold cross-validation (AUCCV = 0.871) and against an external
test set (AUCEXT = 0.917), indicated accurate classification of urine samples
from the affected village and from a reference site. Ten candidate biomarkers
identified at false discovery rates of <0.05 were associated with ATP-binding
cassette (ABC) transporters, possibly related to the disruption of small-molecule
transport in the kidney; amino acid, porphyrin, and chlorophyll metabolism; and
the heme biosynthetic pathway. Collectively, the results suggest that lead Pb is
related to the health effects in individuals residing in ULAB site by alteration
of these biological pathways.
PMID- 29966842
TI - PVCP-based anthropomorphic breast phantoms containing structures similar to
lactiferous ducts for ultrasound imaging: A comparison with human breasts.
AB - The purpose of this work was to obtain an anthropomorphic phantom with acoustic
properties similar to those of breast tissue, possessing lactiferous duct-like
structures, which would be a first for this type of phantom. Breast lesions
usually grow in glandular tissues or lactiferous ducts. Shape variations in these
structures are detectable by using ultrasound imaging. To increase early
diagnosis, it is important to develop computer-aided diagnosis (CAD) systems and
improve medical training. Using tissue-like materials that mimic known internal
structures can help achieve both of these goals. However, most breast ultrasound
phantoms described in the literature emulate only fat tissues and lesion-like
masses. In addition, commercially available phantoms claim to be realistic, but
do not contain lactiferous duct structures. In this work, we collected reference
images from both breasts of ten healthy female volunteers aged between 20 and 30
years using a 10 MHz linear transducer of a B-mode medical ultrasound system.
Histograms of the grey scale distribution of each tissue component of interest,
the grey level means, and standard deviations of the regions of interest were
obtained. Phantoms were produced using polyvinyl chloride plastisol (PVCP)
suspensions. The lactiferous duct-like structures were prepared using pure PVCP.
Solid scatterers, such as alumina (mesh #100) and graphite powders (mesh #140)
were added to the phantom matrix to mimic glandular and fat tissue, respectively.
The phantom duct-like structure diameters observed on B-mode images (1.92 mm +/-
0.44) were similar to real measures obtained with a micrometer (2.08 mm +/-
0.23). The phantom ducts are easy to produce and are largely stable for at least
one year. This phantom allows the researchers to elaborate the structure at their
will and may be used in training and as a reference for development of CAD
systems.
PMID- 29966843
TI - Defect mapping in pipes by ultrasonic wavefield cross-correlation: A synthetic
verification.
AB - This work presents a reverse-time imaging technique by cross-correlating the
forward wavefield with the reverse wavefield for the detection, localization, and
sizing of defects in pipelines. The presented technique allows to capture the
wavefield reflectivity at the places of ultrasonic wave scattering and
reflections. Thus, the method is suitable for detecting pipe defects of either
point-like or finite-size types using data from a pulse-echo setup. By using
synthetic data generated by 3D spectral element pipe models, we show that the 3D
wavefield cross-correlation imaging is capable in the case of cylindrical guided
ultrasonic waves. With a ring setup of transducers, we analyze the imaging
results obtained from the synthetic single-transducer and all-transducer firings.
The presented pipe flaw imaging method is straightforward to carry out using a
suitable wave equation solver. Also, the method does not suffer from long
iterative runs and numerical convergence issues commonly connected with imaging
methods based on either deterministic optimization or statistical inference. The
imaging procedure can be fully baseline-free by performing data processing to
remove direct arrivals from the ultrasound data.
PMID- 29966844
TI - Glutathione-protected gold nanocluster decorated cadmium sulfide with enhanced
photostability and photocatalytic activity.
AB - A Novel glutathione-protected gold nanocluster (Aux-GSH NC) decorated CdS
photocatalyst was prepared using a chemical self-assembly method. After the
photocatalyst was decorated with Aux-GSH NCs, the photocatalytic activity and
photostability of CdS were remarkably enhanced. Compared to pure CdS, the as
prepared CdS-Pt-Auc photocatalyst exhibited 9 times of photocurrent and 2.85
times of photocatalytic activity. More importantly, the photocorrosion of CdS,
which is a critical drawback for CdS-based photocatalysts, was significantly
suppressed. It is believed that the heterostructures and matched energy levels
between CdS and Aux-GSH NCs are the key for enhance catalytic activity and
photostability. The level of LUMO and HOMO of Aux-GSH NCs is higher the
conduction band and valence band of CdS respectively. Through the
heterostructures, the photogenerated electrons of Aux-GSH NCs are injected into
the CdS, while the photogenerated holes of CdS transferred to the Aux-GSH NCs.
The opposite directions of charge migration improves the charge separation
efficiency and average lifetime, which drastically enhances the photoactivity,
and the rapid transferring of holes from CdS to Aux-GSH NCs significantly
suppresses the photocorrosion of CdS.
PMID- 29966845
TI - Morphology-dependent electrochemical performance of Ni-1,3,5
benzenetricarboxylate metal-organic frameworks as an anode material for Li-ion
batteries.
AB - The performance of energy storage materials is substantially dependent on their
nanostructures. Herein, Ni-1,3,5-benzenetricarboxylate metal-organic frameworks
(Ni-BTC MOFs) with different morphologies are controllably synthesized using a
facile solvothermal method by simply adjusting the solvent and their
electrochemical performance as an anode material for lithium-ion batteries is
thoroughly investigated. Among the synthesized Ni-BTC MOFs with different
morphologies, a hierarchical mesoporous flower-like Ni-BTC MOF (Ni-BTCEtOH)
assembled from two-dimensional nanosheets shows the best electrochemical
properties including a high capacity of 1085 mA h g-1 at 100 mA g-1 (358 mA h g-1
at 5000 mA g-1), excellent cycling stability at 1000 mA g-1 for 1000 cycles, and
great rate performance, which is superior to most of the reported MOF-based anode
materials for lithium-ion batteries. The outstanding electrochemical performance
of Ni-BTCEtOH is originated from its unique and stable hierarchical mesoporous
morphology with a high specific surface area and improved electrical/ionic
conductivity. Moreover, our study demonstrates that the charge-discharge
mechanism of the Ni-BTCEtOH electrode involves the insertion/extraction of Li
ions to/from the organic moieties in Ni-BTCEtOH during the charge-discharge
process without the direct engagement of Ni2+. This work highlights that the
nanostructure design is an effective strategy to obtain promising energy storage
materials.
PMID- 29966846
TI - In-situ wrapping of tin oxide nanoparticles by bacterial cellulose derived carbon
nanofibers and its application as freestanding interlayer in lithium sulfide
based lithium-sulfur batteries.
AB - Lithium-Sulfur (Li-S) batteries are mostly known for their high energy density
and cost-effectiveness. However, their intrinsic problems hinder their
implementation into the marketplace. The most pronounced problems are the
parasitic reactions which occur between lithium polysulfides species and lithium
metal anode, the volume expansion of sulfur (80%) at the end of discharge and the
safety issues which are linked with the use of lithium metal. Herein this work,
two approaches are applied to prevent these effects; one approach is the use of
Li2S as cathode material, instead of starting from sulfur powder, both to
circumvent the volume expansion of sulfur taking place during discharge and to
enable lithium-free anodes cell assembling (i.e. Si-Li2S or Sn-Li2S cell
configurations). Second approach deals with the lithium anode protection by SnO2
containing freestanding pyrolyzed bacterial cellulose interlayers located between
anode and cathode electrodes. Since bacterial celluloses are formed in the
presence of SnO2 nanoparticles, the resulting structure enables intimate contact
between carbon and SnO2 nanoparticles. By employing Li2S cathode and freestanding
interlayer concurrently, 468 mAh g-1 discharge capacity is obtained at C/10
current density over 100 cycles.
PMID- 29966847
TI - Phosphorus-doped cobalt-iron oxyhydroxide with untrafine nanosheet structure
enable efficient oxygen evolution electrocatalysis.
AB - Although explosive progresses have been achieved in the field of water splitting,
the design and development of stable and inexpensive electrocatalysts for oxygen
evolution remain a formidable challenge. Herein, the cost-efficient two
dimensional (2D) phosphorus-doped CoFe oxyhydroxide nanosheets (denoted as CoFeP
NSs) are successfully engineered and showing exceptional oxygen evolution
reaction (OER) activity and chemical stability in 1 M KOH solution. This unique
2D nanosheet structure facilitates the mass transfer and electron transport,
resulting in the remarkable OER activity that delivers a current density of 10 mA
cm-2 at a low overpotential of 305 mV with an ultra-small Tafel slope 49.6
mV/dec. More significantly, the doped P also plays a vital role in modulating the
surface active sites, leading to the substantial enhancement of electrocatalytic
performances. Our study provides a facile one-pot method for the successful
fabrication of 2D P-doped CoFe NSs which display superior electrocatalytic
performance, shedding great promise for environment and energy-related fields.
PMID- 29966848
TI - Investigation of the adsorption mechanisms of Pb(II) and 1-naphthol by beta
cyclodextrin modified graphene oxide nanosheets from aqueous solution.
AB - beta-cyclodextrin decorated graphene oxides (beta-CD-GO) was prepared by using an
in-situ aggregation treatment, and used to remove inorganic (Pb(II)) and organic
pollutants (1-naphthol) from water environment. The batch adsorption experiments
of as-prepared beta-CD-GO were carried out as a function of pH values, initial
Pb(II) and 1-naphthol concentration, ionic strength, contact time and
temperature. beta-CD-GO kinetic results indicated that the adsorption was
dominated by chemisorptions and followed a pseudo-second order model. The maximum
adsorption capacities of beta-CD-GO toward Pb(II) and 1-naphtholon the base of
the Langmuir model were 149.56 and 207.6 mg.g-1 at 293 K, respectively. The
thermodynamic experiments revealed that the adsorption of Pb(II) and 1-naphthol
was spontaneous and endothermic. The surface compexation, hydrogen bonds and pi
pi interactions contributed to Pb(II) and 1-naphthol adsorption by means of the
hydroxy and carboxyl functional groups on the surface of the beta-CD-GO. The
experimental results indicate that the beta-CD-GO is an excellent composite for
the elimination of Pb(II) and 1-naphthol from wastewater.
PMID- 29966849
TI - Electrocatalytic enhancement of platinum and palladium metal on polydopamine
reduced graphene oxide support for alcohol oxidation.
AB - The objective of our work is to improve low-temperature fuel cell catalysts by
increasing the surface area to augment the efficiency of catalytic reactions.
Reduced graphene oxide (rGO) supports were prepared by adding N-containing
derivatives of polydopamine (PDA) and loading of Pt and Pt-based metal alloy
nanoparticles were accomplished for catalyst preparation. To study the effects of
surface modification on catalyst activity, the GO surfaces modified by addition
of PDA (PDA-rGO) were richer in oxygen- and nitrogen-containing functional
groups, which reduced the number of graphene defects. Reduction of metals (M =
Pt, Pd, PtxPdy where x and y = 1-3) by NaBH4 produced M/GO (metal on GO) and
M/PDA-rGO (metal on PDA-rGO) catalysts. Examination of morphology and chemical
composition confirmed that the existence of particle size on M/PDA-rGO catalysts
was smaller than that on M/GO catalysts in agreement with calculated
electrochemically active surface areas (ECSA). Electrochemical analysis was
conducted to evaluate the catalyst activity and stability. The prepared catalysts
had significantly greater surface areas as a result of association between the
metal nanoparticles and the oxygen and nitrogen functional groups on the rGO
supports. The catalysts also exhibited lower onset potentials and greater current
intensities, If/Ib values, and long-term stabilities for methanol and ethanol
oxidation compared with those of commercial PtRu/C. Moreover, the diameter of the
Nyquist plot of the catalysts on PDA-rGO were smaller than that of the catalysts
M/GO. The results suggest that variation of the PtxPdy atomic ratio on carbon
nanocomposites is an encouraging means of enhancing electrocatalytic performance
in direct alcohol fuel cell applications.
PMID- 29966850
TI - Adverse effects of GHB-induced coma on long-term memory and related brain
function.
AB - BACKGROUND: Gamma-Hydroxybutyric acid (GHB) is a drug of abuse associated with
increasing numbers of GHB-dependent patients and emergency attendances often
related to GHB-induced coma. Animal studies suggest that GHB induces oxidative
stress in the hippocampus, resulting in memory impairments. However, the
consequences of chronic GHB use and GHB-induced coma on human brain function and
cognition are unknown. METHODS: We recruited 27 GHB users with >=4 GHB-induced
comas (GHB-Coma), 27 GHB users without a coma (GHB-NoComa), and 27 polydrug users
who never used GHB (No-GHB). Participants completed verbal and spatial memory
tests and an associative memory encoding task during functional magnetic
resonance imaging (fMRI) to probe hippocampus functioning. RESULTS: The GHB-Coma
group showed a lower premorbid IQ (p = 0.006) and performed worse on the verbal
memory test (p = 0.017) compared to the GHB-NoComa group, despite exhibiting
similar levels of education. Compared with the other two groups, the GHB-Coma
group showed lower left hippocampus (pSVC = 0.044) and left lingual gyrus (pFWE =
0.017) activity, and a trend for lower hippocampal functional connectivity with
the left superior temporal cortex during performance of the associative memory
encoding task (pFWE = 0.063). No significant differences were observed between
the GHB-NoComa group and the No-GHB group. CONCLUSIONS: These results suggest
that multiple GHB-induced comas, but not the use of GHB per se, are associated
with alterations of memory performance and memory-related brain, although no
causal link can be inferred from this cross-sectional study. The results
highlight the need for public awareness to minimize the negative health
consequences of recreational GHB use, in particular when related with GHB-induced
comas.
PMID- 29966852
TI - Automatic visual-spatial perspective taking in alcohol-dependence: A study with
happy emotional faces.
AB - BACKGROUND: Understanding the world from another's perspective is an important
and potentially automatic human process which is crucial for efficient social
interactions. However, while deficits have repeatedly been described for various
interpersonal abilities in alcohol-dependence (AD), only one previous study has
investigated perspective taking in this pathology. AIM: The current study aimed
to explore further how AD affects visual-spatial perspective taking (VSPT) by
examining the effect of positive emotional stimuli on VSPT in both an AD and non
AD sample. METHODS: Reaction times (RT) for simple spatial judgments were
measured. Participants made these judgments from their perspective, but judgments
were either congruent or incongruent with the perspective of another agent. The
emotion conveyed by that agent (happy or neutral) was manipulated across trials.
RESULTS: Compared to baseline, both AD and non-AD groups displayed delayed RTs
for spatial judgments when these were incongruent with the perspective of a happy
agent (the expected VSPT RT cost, indicating automatic VSPT). The AD, but not the
non-AD group, further displayed a VSPT RT cost when the agent expressed a neutral
emotion. CONCLUSION: There was no evidence that AD compromised automatic VSPT.
However, as in previous research, AD was associated with differences in the
processing of emotional stimuli. Future research should explore which 'real
world' settings are likely to trigger social confusion and misunderstanding.
PMID- 29966851
TI - Do naloxone access laws increase outpatient naloxone prescriptions? Evidence from
Medicaid.
AB - BACKGROUND: Naloxone is a prescription medication that can quickly and
effectively reverse opioid overdose. Medicaid is a major payer of substance use
disorder services, and Medicaid beneficiaries experience especially high rates of
opioid overdose. As opioid overdose rates have risen sharply, every state has
modified its laws to make naloxone easier to access. The aim of this paper is to
determine whether implementation of different provisions of naloxone access laws
led to increased naloxone dispensing financed by Medicaid. METHODS: We reviewed
naloxone legislation passed by every state between 2007 and 2016. We used the
Medicaid State Drug Utilization dataset to examine the effect of different types
of state naloxone access law provisions, separately and as a whole, on the number
of outpatient naloxone prescriptions reimbursed by Medicaid from 2007 to 2016. We
included state-level covariates in our models that may be correlated with
naloxone utilization in Medicaid and passage of naloxone access laws. RESULTS: We
found that the presence of any naloxone law was significantly associated with
increases in outpatient naloxone reimbursed through Medicaid. Laws containing
standing order provisions were most consistently associated with increases in
naloxone dispensing across models. Standing order provisions led on average to an
increase of approximately 33 naloxone prescriptions per state-quarter, which is
equivalent to 74% of the average number of naloxone prescriptions per state
quarter. CONCLUSIONS: Naloxone access laws, particularly those with standing
order provisions, appear to be an effective policy approach to increasing
naloxone access among Medicaid beneficiaries.
PMID- 29966853
TI - Comparative assessment of metal-specific adipogenic activity in zinc and vanadium
citrates through associated gene expression.
AB - Diabetes mellitus comprises a group of metabolic abnormalities due to insulin
deficiency and/or resistance. Obesity contributes to diabetes, with a strong
causal relationship existing between diabetes and insulin resistance, especially
in patients with Diabetes mellitus II. Adipocytes emerge as key constituents of
adipose tissue physiology. In their pre-mature form to mature state
transformation, adipocytes fully exemplify one of the key adipogenic actions of
insulin. Poised to a) gain insight into adipogenesis leading to antidiabetic
factors, and b) investigate adipogenesis through careful examination of insulin
contributions to interwoven mechanistic pathways, a systematic comparative study
was launched involving well-defined metal-citrates (zinc and vanadium), the
chemical reactivity of which was in line with their chemistry under physiological
conditions. Selection of the specific compounds was based on their common aqueous
coordination chemistry involving the physiological chelator citric acid. Cellular
maturation of pre-adipocytes to their mature form was pursued in the presence
absence of insulin and employment of closely linked genetic targets, key to
adipocyte maturation (Peroxisome proliferator-activated receptor gamma (PPAR
gamma), Glucose transporter 1,3,4 (GLUT 1,3,4), Adiponectin (ADIPOQ), Glucokinase
(GCK), and Insulin receptor (INS-R)). The results show a) distinct adipogenic
biological profiles for the metalloforms involved in a dose-, time- and nature
dependent manner, and b) metal ion-specific adipogenic response-signals at the
same or higher level than insulin toward all selected targets. Collectively, the
foundations have been established for future exploitation of the distinct metal
specific adipogenic factors contributing to the functional maturation of adipose
tissue and their use toward hyperglycemic control in Diabetes mellitus.
PMID- 29966854
TI - Revealing how interfaces in stacked thin fibrous layers affect liquid ingress and
transport properties by single-sided NMR.
AB - Offering multifaceted applications, thin fibrous porous materials are mostly used
in stacks of layers, each layer having a defined functionality. Since only a few
pores exist across a layer a couple of hundred microns thick, the interface
between layers may significantly affect liquid ingress. Thus, the main objective
of the study is to substantiate that an interface layer is present during liquid
infiltration between stacked thin fibrous layers and that it affects the fluid
transport properties. A compact single-sided NMR device with a low static
gradient of about 2 T/m perpendicular to the sensor surface and a uniform
magnetic field in lateral directions was used to profile a 2-mm thick slice in
one shot. The liquid ingress into the thin fibrous layers and their interfaces
was visualized by Fourier-transforming the NMR signal and processing the time
dependent 1D profiles with a newly developed mathematical method. The flow
characteristics and liquid distribution profiles of a 400-um thick layer were
compared with those of two stacked 200-um thick layers from the same material but
with an interface between them. The results show major differences in
distributions and flow dynamics for the single and dual layer cases, which reveal
the importance of the interface in fluid flow.
PMID- 29966855
TI - Banning pre-event rumination in social anxiety: A preliminary randomized trial.
AB - BACKGROUND AND OBJECTIVES: Pre-event rumination has a clear role in maintaining
social anxiety according to cognitive models. However, it is unclear what
specific strategies can address pre-event rumination for individuals diagnosed
with SAD. The current study aimed to determine the effectiveness of a brief
intervention on multiple aspects of pre-event rumination, state anxiety and
performance and threat appraisals. Additionally, the trajectory of pre-event
rumination was investigated over four days. METHODS: Participants with SAD were
informed they would be required to complete a speech task in four days' time and
were randomised to an intervention (n = 27) or a non-active control group (n =
25). The intervention group were instructed to "ban" pre-event rumination using a
metacognitive therapy technique known as detached mindfulness. All participants
completed daily measures of pre-evet rumination that assessed frequency,
uncontrollability, engagement and distress associated with pre-event rumination.
On the day of the speech task, participants also completed state and cognitive
measures before delivering the speech task. RESULTS: The intervention group
reported reduced frequency, uncontrollability and distress associated with pre
event rumination, compared to the control group. There was no difference between
groups for performance and threat appraisals as well as state anxiety. Rumination
is a stable and robust process, with an increase in frequency and associated
distress 24 hours before a feared social situation. LIMITATIONS: The lack of an
active control group precludes comparisons to more traditional cognitive
behavioural therapy strategies for pre-event rumination. CONCLUSIONS: Pre-event
rumination is a durable process but banning pre-event rumination using
metacognitive therapy techniques shows promise for specifically addressing this
maladaptive process.
PMID- 29966856
TI - Cross-cultural adaptation and validity of the Italian version of the Central
Sensitization Inventory.
AB - BACKGROUND: Central sensitization (CS) is an important feature in patients with
chronic pain. The Central Sensitization Inventory (CSI) was developed with the
goal of detecting the patients' symptoms related to CS. OBJECTIVES: This study
aimed at cross-culturally adapting the CSI into Italian, and at assessing its
structural and construct validity in patients with different chronic pain
disorders. DESIGN: Clinimetric study. METHODS: The Italian version of the CSI
(CSI-I) was generated following forward and backward translations, expert
committee review, and pilot-testing. Patients with pain for >=3 months were
eligible if diagnosed with: low back pain (LBP), temporomandibular disorder
(TMD), hand osteoarthritis (HOA), fibromyalgia (FM), or rheumatoid arthritis
(RA). Structural validity was assessed with exploratory factor analysis and
parallel analysis based on minimum rank factor analysis; construct validity was
evaluated by testing ten hypotheses on: 1) expected differences between relevant
subgroups, 2) expected correlations with other instruments measuring pain
intensity, physical functioning, psychological functioning, headache symptoms,
and pain self-efficacy. RESULTS: 220 patients were included: 35% with LBP, 17%
with TMD, 19% with HOA, 9% with FM, and 20% with RA. Factor analyses revealed
that the CSI-I is a unidimensional instrument. Construct validity was
satisfactory since 80% of the hypotheses were met. CONCLUSIONS: The CSI-I was
successfully developed and exhibited satisfactory validity in patients with
chronic pain. Its reliability, responsiveness and content validity should be
investigated in future studies. Until robust evidence indicates a strong
relationship between CS and the CSI-I, caution should be adopted in claiming that
the CSI-I measures CS.
PMID- 29966858
TI - The effects of training impulse control on simulated driving.
AB - There is growing interest in young driver training that addresses age-related
factors, including incompletely developed impulse control. Two studies
investigated whether training of response inhibition can reduce risky simulated
driving in young drivers (aged 16-24 years). Each study manipulated aspects of
response inhibition training then assessed transfer of training using simulated
driving measures including speeding, risky passing, and compliance with traffic
controls. Study 1 (n = 65) used a Go/No-go task, Stop Signal Task and a Collision
Detection Task. Designed to promote engagement, learning, and transfer, training
tasks were driving-relevant and adaptive (i.e. difficulty increased as
performance improved), included performance feedback, and were distributed over
five days. Control participants completed matching "filler" tasks. Performance on
trained tasks improved with training, but there was no significant improvement in
simulated driving. Study 2 enhanced response inhibition training using Go/No-go
and SST tasks, with clearer performance feedback, and 10 days of training.
Control participants completed testing only, in order to avoid any possibility of
training response inhibition in the filler tasks. Again performance on trained
tasks improved, but there was no evidence of transfer of training to simulated
driving. These findings suggest that although training of sufficient interest and
duration can improve response inhibition task performance, a training schedule
that is likely to be acceptable to the public does not result in improvements in
simulated driving. Further research is needed to investigate whether response
inhibition training can improve risky driving in the context of real-world
motivations for risky driving.
PMID- 29966859
TI - Estimating factors of individual and regional characteristics affecting the drink
driving recidivism.
AB - Traffic violations, particularly drink driving, are a menace to the drivers
themselves, and to other road users. Drink driving crashes often cause death or
serious injury to the driver. Understanding the recidivism effect factor of drink
driving is essential for designing effective countermeasures. This study is based
on register-based data from the National Police Agency, Ministry of the Interior
of Taiwan and monthly administrative area information from 2012 to 2015 for the
entire population. Hence, this study not only focuses on the effect factor and
violation differences between recidivists and non-recidivists, but discusses the
entire regional characteristics effect for recidivism. The purpose of this study
is to offer a comprehensive econometrical framework, using a multilevel random
effect logistic model, which highlights important contributors to drink driving
recidivism from regional attributes. As the study findings from our empirical
results indicate, there are statistically significant differences with drink
driving in administrative areas, depending on the number of report on drink
driving by police, divorce rate of the population, alcohol consumption, number of
community security patrol teams, number of bus trips, and level of education. The
results of this study provide suggestions to the government for enhancing
community security and developing public transportation, both of which can
effectively decrease drink driving recidivism and improve public road safety.
PMID- 29966860
TI - A simple end-point assay for calcium channel activity.
AB - Cellular calcium signaling events are transient. Hence they are observed in real
time using fluorescence imaging or electrophysiological methods that require
sophisticated instrumentation and specialized skills. For high throughput assays
simple and inexpensive techniques are desirable. Many calcium channels that serve
as drug targets have subtypes arising from diverse subunit combinations. These
need to be targeted selectively for achieving efficacy and for avoiding side
effects in therapies. This in turn increases the number of calcium channels that
act as drug targets. We report a novel method for intracellular calcium sensing
that utilizes the calcium dependent stable interaction between CaM kinase II
(CaMKII) and its ligands such as the NMDA receptor subunit GluN2B. The CaMKII
GluN2B complex formed persists as a memory of the transient increase in calcium.
In a cell-based assay system GFP-alpha-CaMKII expressed in the cytosol responds
to calcium by translocating towards GluN2B sequence motif exogenously expressed
on mitochondria or endoplasmic reticulum. The resulting punctate fluorescence
pattern serves as the signal for intracellular calcium release. The pattern is
stable, unaffected by sample processing and is observable without real time
imaging. The activities of calcium channel proteins heterologously expressed in
HEK-293 cells were detected with specificity using this technique. A calcium
sensor vector and a calcium sensor cell line were developed as tools to perform
this technique. This technique being simple and less expensive could
significantly facilitate high throughput screening in calcium channel drug
discovery.
PMID- 29966861
TI - It wasn't me: The role of perspective in self-perceptions of responsibility.
AB - Perceiving oneself as agentic is dependent upon the integration of conscious
intention, a corresponding outcome, and body-congruent sensorimotor information.
Altering these critical cues, such as the vantage point from which an event is
viewed, can have a notable impact on one's sense of agency, including an
increased sense of ownership over another person's actions or a reduced sense of
responsibility (or control) over one's own actions. In three studies, we
investigated whether mentally simulated and written perspectives could have
similar effects. Participants were asked to consider ambiguous actions from
either a first-person or a third-person perspective. Results revealed that third
person perspectives reduced judgments of personal responsibility for positive and
negative actions. Perceptions of personal action execution as well as the
perceived overlap between one's real and imagined self were identified as
mediators of the reduced sense of responsibility that characterized negative, but
not positive, events constructed from a third-person perspective.
PMID- 29966862
TI - Cognitions about time affect perception, behavior, and physiology - A review on
effects of external clock-speed manipulations.
AB - Our understanding of (altered) time perception may benefit from investigating its
potential effects upon other psychological and physiological parameters. To date,
however, only a few rather isolated studies have experimentally manipulated the
subjective passage of time or the amount of apparently elapsed duration in order
to investigate such effects. Based on our review of these studies, first, altered
time perception can be induced effectively by means of rigged (accelerated or
decelerated) external clocks, second, these clock-speed manipulations remain
unnoticed by most participants, and third, several psychological, cognitive,
behavioral, and physiological variables can be affected, e.g., fatigue, hunger,
pain perception. However, the existing studies on time-perception manipulation do
not systematically relate to each other and the underlying mechanisms of the
observed effects are poorly understood. Based on cognitive appraisal theories and
the given empirical results, we propose a cognitive framework for interpreting
and explaining the effects of manipulations of time perception.
PMID- 29966863
TI - Dose Escalation of Lobaplatin Concurrent with IMRT for the Treatment of Stage III
IVb NPC: A Phase I Clinical Trial.
AB - The maximum tolerated dose (MTD) of lobaplatin as a single agent chemotherapy
concurrent with intensity-modulated radiotherapy (IMRT) in Asian population with
nasopharyngeal carcinoma (NPC) remains unclear. From June 2016 to December 2017,
17 patients diagnosed with stage III-IVb NPC from an Asian population were
prospectively enrolled. Patients were administered lobaplatin with 25-50 mg/m2
escalation of dosage on day 1. Every 21 days (days 1, 22, and 43) during
radiotherapy, cycles were repeated. We administered radiotherapy as 2.12-2.27 Gy
per fraction with five daily fractions each week for 6 to 7 weeks. The evaluation
of lobaplatin-related toxic effects was based on the Common Terminology Criteria
for Adverse Events version 4.0. During the weekly treatment period, complete
blood counts and biochemistry were performed. Dose-limiting toxicities (DLTs)
were determined by the following events during any cycle in which lobaplatin was
administered. Each dose group consisted of at least three cases. We proceeded to
the subsequent dose group in the absence of DLT with a dose increment of 5 mg/m2
until DLT occurred. Periods from 1 week prior to the chemotherapy initiation to 3
weeks after the last chemotherapy were defined as DLT observation periods. MTD
was determined by the dose that was immediately below the dose that produced DLT.
After analysis, DLT occurred in three patients, including a group with two of
three patients in 45 mg/m2 lobaplatin and another group with one of five patients
in 40 mg/m2 lobaplatin. No grade 3-4 toxicity was observed in patients treated
with lobaplatin <40 mg/m2. The tumor response rate at 12 weeks after treatment
was 100%. In summary, lobaplatin concurrent with IMRT was active in stage III-IVb
NPC, and the MTD for the lobaplatin as single-agent chemotherapy was 40 mg/m2
when combined with IMRT in an Asian population. This trial is registered with
ClinicalTrials.gov, number NCT03188497.
PMID- 29966865
TI - An exploratory study of Eastern Ugandan adolescents' descriptions of social
withdrawal.
AB - INTRODUCTION: Researchers have identified a variety of motivations for solitude
and for social withdrawal. These motivations may differ across cultures. The
purpose of this study was to explore Ugandan adolescents' descriptions of
solitude and social withdrawal, with the aim of guiding future research on social
withdrawal in Uganda. METHODS: Ugandan adolescents' (M = 14.23 years old, SD =
1.63 years) descriptions of solitude and social withdrawal were investigated in a
cross-sectional, exploratory study. The sample (N = 219 [106 girls, 90 boys, 23
missing sex data]) was drawn from two primary schools and a secondary school in
Eastern Uganda. Adolescents' responses to open-ended questionnaire items about
general solitude, conflicted motivations for social withdrawal, and non
conflicted motivation for social withdrawal were coded and categorized. RESULTS:
Some of the adolescents' descriptions were consistent with the literature. For
example, they described shyness and internalizing emotions, externalizing and
socially incompetent behaviors, and poor peer relationships. Some descriptions
were unique and likely reflected Uganda's challenges, for instance, family or
household factors such as being an orphan. CONCLUSIONS: Results underscored the
importance of exploring contextual processes (e.g., parental loss) that might
affect Ugandan adolescents' solitude. More generally, the results suggested that
solitude should be researched using a broad, synergistic lens that incorporates
potential determinants from adolescents and their environments at multiple levels
(e.g., person, peer, household, culture).
PMID- 29966864
TI - Biphasic Alteration of Butyrylcholinesterase (BChE) During Prostate Cancer
Development.
AB - Butyrylcholinesterase (BChE) is a plasma enzyme that hydrolyzes ghrelin and
bioactive esters, suggesting a role in modulating metabolism. Serum BChE is
reduced in cancer patients. In prostate cancer (PC), the down-regulation is
associated with disease recurrence. Nonetheless, how BChE is expressed in PC and
its impact on PC remain unclear. We report here the biphasic changes of BChE
expression in PC. In vitro, BChE expression was decreased in more tumorigenic PC
stem-like cells (PCSLCs), DU145, and PC3 cells compared to less tumorigenic non
stem PCs and LNCaP cells. On the other hand, BChE was expressed at a higher level
in LNCaP cells than immortalized but non-tumorigenic prostate epithelial BPH-1
cells. In vivo, BChE expression was up-regulated in DU145 xenografts compared to
LNCaP xenografts; DU145 cell-derived lung metastases displayed comparable levels
of BChE as subcutaneous tumors. Furthermore, LNCaP xenografts produced in
castrated mice exhibited a significant increase of BChE expression compared to
xenografts generated in intact mice. In patients, BChE expression was down
regulated in PCs (n = 340) compared to prostate tissues (n = 86). In two
independent PC populations MSKCC (n = 130) and TCGA Provisional (n = 490), BChE
mRNA levels were reduced from World Health Organization grade group 1 (WHOGG 1)
PCs to WHOGG 3 PCs, followed by a significant increase in WHOGG 5 PCs. The up
regulation was associated with a reduction in disease-free survival (P = .008).
Collectively, we demonstrated for the first time a biphasic alteration of BChE,
its down-regulation at early stage of PC and its up-regulation at advanced PC.
PMID- 29966866
TI - Non-linear dynamics of cardiac autonomic activity during cycling exercise with
varied cadence.
AB - In recent years, complex models of cardiac regulation have integrated heart rate
variability (HRV) as a measure of the cardiac autonomic activity during exercise.
Using detrended fluctuation analysis (DFA) technique, the present study examines
the influence of cycling cadence and exercise duration on non-linear dynamics of
HRV. Sixteen trained cyclists performed a 60-minute exercise bout at 90% of the
individual anaerobic threshold on a bicycle ergometer. Cadence was changed every
10 min (90-120-60-120-60-90 rpm). Heart rate (HR) and RR-intervals were recorded
continuously during exercise. HRV time domain measures (meanRR, SDNN) and
correlation properties were analyzed using short-term scaling exponent alpha1 of
DFA. Moreover, blood lactate (La) and rating of perceived exertion (RPE) were
recorded at regular intervals at the end of condition. HR, La and RPE increased
significantly at 120 rpm compared to 60 rpm. In contrast, all analyzed HRV
parameters (meanRR, SDNN, DFA-alpha1) showed a significant decrease during
cycling at 120 rpm compared to 60 rpm. The comparison of the first and last 10
min with the same cadence indicates a significant increase in HR and RPE, but
also a significant decrease in all analyzed HRV measures. The decrease of HRV
values over time and in relation to the increase in cadence indicates a decrease
in the overall variability as well as a reduction in complexity of the RR
interval-fluctuations due to the increased organismic demands. Therefore, the
decrease of DFA-alpha1 might be associated with a withdrawal of the organismic
system aiming at the maintenance of the homeostasis under the control of the
central nervous system. In this context, non-linear HRV analyses provide a more
systemic view of cardiac regulation during exercise.
PMID- 29966867
TI - Differences in accuracy and vividness of motor imagery in children with and
without Developmental Coordination Disorder.
AB - Motor imagery (MI) provides a unique window on the integrity of movement
representation. Studies have shown that children with Developmental Coordination
Disorder (DCD) experience problems with tasks thought to rely on an internal
model of movements. Therefore, the purpose of this study was to compare MI
accuracy and MI vividness between typically developing (TD) and children with
DCD. Ninety-three children with ages between 7 and 12 years (TD: n = 51; DCD: n =
42) were tested with the Movement Imagery Questionnaire (MIQ-c) to assess MI
vividness and the Florida Praxis Imagery Questionnaire (FPIQ) to assess MI
accuracy. To compare differences between the groups for each assessment and in
the subscales, two separate general linear model analyses were conducted: A 2 * 3
(Group [TD, DCD] * Subscales [internal visual imagery, external visual imagery,
kinesthetic imagery]) for MI vividness and a 2 * 4 (Group [TD, DCD] * Subscales
[position, object, kinesthetic, action]) for MI accuracy. Results indicated that
children with DCD scored significantly lower (p < .05) on MI accuracy than TD
children, but there were no significant differences between the groups on MI
vividness. Additionally, there were significant differences in the subscales for
both measurements of MI. Specifically, results showed lower scores overall for
the kinesthetic subscale. These findings indicate that the MI deficit seen in
children with DCD is probably associated with MI accuracy, not MI vividness.
These results suggest the need of further exploration into specific measurements
of MI in children with DCD.
PMID- 29966868
TI - 2-S-cysteinylhydroquinone is an intermediate for the firefly luciferin
biosynthesis that occurs in the pupal stage of the Japanese firefly, Luciola
lateralis.
AB - Firefly luciferin is a natural product that is well-known to function as the
substrate of the bioluminescence reaction in luminous beetles. However, the
details of the biosynthetic system are still unclear. In this study, we showed by
LC-MS/MS analysis that stable isotope-labeled 2-S-cysteinylhydroquinone was
incorporated into firefly luciferin in living firefly specimens. Comparison of
the incorporation efficiency among the developmental stages suggested that
firefly luciferin is biosynthesized predominantly in the pupal stage. We also
accomplished the in vitro biosynthesis of firefly luciferin using 2-S
cysteinylhydroquinone and the crude buffer extract of firefly pupae, suggesting
the presence of a biosynthetic enzyme in the pupal extract.
PMID- 29966869
TI - Design and synthesis of gallocyanine inhibitors of DKK1/LRP6 interactions for
treatment of Alzheimer's disease.
AB - Based on NCI8642, a series of gallocyanine derivatives was synthesized with
modifications of the substituent groups in position 1, 2 and 4 of the
phenoxazinone scaffold. The effectiveness of gallocyanines to inhibit DKK1/LRP6
interactions and Tau phosphorylation induced by prostaglandin J2 and DKK1 was
elucidated by both experimental data and molecular docking simulations. Bis
alkylated with flexible alkyl ester groups on C1 and bis-benzyl gallocyanines
provided the most active inhibitors, while amino derivatives on C2 of NCI8642
that have alkoxy or benzyloxy substituents on C4, were less active. Furthermore,
it is shown that treating of SHSY5Y cells with NCI8642 derivatives activates Wnt
signaling and increases the levels of pGSK3beta kinase and beta-catenin.
PMID- 29966870
TI - Design and synthesis of donepezil analogues as dual AChE and BACE-1 inhibitors.
AB - Multi-target-directed ligands (MTDLs) centered on beta-secretase 1 (BACE-1)
inhibition are emerging as innovative therapeutics in addressing the complexity
of neurodegenerative diseases. A new series of donepezil analogues was designed,
synthesized and evaluated as MTDLs against neurodegenerative diseases. Profiling
of donepezil, a potent acetylcholinesterase (hAChE) inhibitor, into BACE-1
inhibition was achieved through introduction of backbone amide linkers to the
designed compounds which are capable of hydrogen-bonding with BACE-1 catalytic
site. In vitro assays and molecular modeling studies revealed the dual mode of
action of compounds 4-6 against hAChE and BACE-1. Notably, compound 4 displayed
potent hAChE inhibition (IC50 value of 4.11 nM) and BACE-1 inhibition (IC50 value
of 18.3 nM) in comparison to donepezil (IC50 values of 6.21 and 194 nM against
hAChE and BACE-1, respectively). Moreover, 4 revealed potential metal chelating
property, low toxicity on SH-SY5Y neuroblastoma cells and ability to cross the
blood-brain barrier (BBB) in PAMPA-BBB assay which renders 4 a potential lead for
further optimization of novel small ligands for the treatment of Alzheimer's
disease.
PMID- 29966871
TI - Design, synthesis, biological activities and DFT calculation of novel 1,2,4
triazole Schiff base derivatives.
AB - Series of 1,2,4-triazole Schiff bases (2a-2d, 2f-2h and 3a-3h) have been designed
and synthesized. The structure of title compounds was confirmed on the basis of
their spectral data and elemental analysis. All the target compounds were
screened for their in vitro antifungal activity and antibacterial activity. Two
of the tested compounds (2a and 2b) exhibited significant antifungal activity
against most fungi, especially compound 2a showed better antifungal activity than
triadimefon. Meanwhile, the antibacterial activity assay also indicated compound
2a exhibited excellent antibacterial activities comparable to chloramphenicol.
The SAR manifested no substitution at position 5 of the triazole ring caused an
increase in activity, and 3-phenoxy phenyl group introduced in 1,2,4-triazole
scaffold can enhance the antibacterial activity. The DFT calculation indicated
triazole ring, S atom and benzene ring in both of the 2a and 3a make a major
contribution to the activity.
PMID- 29966872
TI - The zinc - but not cadmium - containing zeta-carbonic from the diatom
Thalassiosira weissflogii is potently activated by amines and amino acids.
AB - The activation of the zeta-class carbonic anhydrase (CAs, EC 4.2.1.1) from the
diatom Thalassiosira weissflogii (TweCAzeta) incorporating both Zn(II) and Cd(II)
at the active site, was investigated for the first time, using a panel of natural
and non-natural amino acids and amines. CdTweCAzeta was completely insensitive to
activation, whereas all these compounds were effective activators of the zinc
containing enzyme ZnTweCAzeta, with activation constants ranging between 92 nM
and 37.9 uM. The most effective ZnTweCAzeta activators were l-adrenaline, 1-(2
aminoethyl)-piperazine and 4-(2-aminoethyl)-morpholine, with KAs in the range of
92-150 nM. l-His, l- and d-Tyr and some pyridyl-alkylamines, had KAs in the range
of 0.62-0.98 uM, whereas l-/d-DOPA, d-Trp, histamine, serotonin and l-Asn were
the next most efficient activators, with KAs in the range of 1.27-3.19 uM. The
least effective activators were l-Phe (KA of 15.4 uM) and l-Asp (KA of 37.9 uM).
This in vitro study may be useful for a more complete understanding of the
activation processes of various CA enzyme families, of which the zeta-class was
scarcely investigated.
PMID- 29966873
TI - Biological properties and structural study of new aminoalkyl derivatives of
benzimidazole and benzotriazole, dual inhibitors of CK2 and PIM1 kinases.
AB - The new aminoalkyl-substituted derivatives of known CK2 inhibitors 4,5,6,7
tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt)
were synthesized, and their influence on the activity of recombinant human CK2
alpha, CK2 holoenzyme and PIM1 kinases was evaluated. All derivatives inhibited
the activity of studied kinases and the most efficient were aminopropyl
derivatives 8b and 14b. These compounds also exerted inhibition of cancer cell
lines - CCRF-CEM (acute lymphoblastoid leukemia), MCF-7 (human breast cancer),
and PC-3 (prostate cancer) proliferation and their EC50 is comparable with the
value for clinically studied CK2 inhibitor CX-4945. Preliminary structure
activity relationship analysis indicated that the spacer length affected
antitumor potency, and two to three methylene units were more favorable. The
complex of CK2 alpha1-335/8b was crystallized, both under high-salt conditions
and under low-salt conditions giving crystals which diffracted X-rays to about
2.4 A resolution, what enabled the determination of the corresponding 3D
structures.
PMID- 29966874
TI - Design, synthesis and molecular modeling study of certain 4
Methylbenzenesulfonamides with CDK2 inhibitory activity as anticancer and radio
sensitizing agents.
AB - Two series of 2-aminopyridine derivatives 6-17 and tyrphostin AG17 analogs 18-22
bearing 4-methylbenzenesulfonamide moiety were designed and synthesized as
anticancer compounds. The synthesized compounds were biologically evaluated for
their cytotoxic activity against human breast cancer cell line MCF-7. From 2
aminopyridine and tyrphostin AG17 series, compounds 14, 16 and 20 showed the best
activities with IC50 values of 20.4, 18.3 and 26.3 uM, respectively compared to
E7070 IC50 36.3 uM. Further biological evaluation of 14, 16 and 20 against cyclin
dependent kinase-2 (CDK2) revealed good inhibitory activity with IC50 of 2.53,
1.79 and 2.92 uM, respectively compared to roscovitine IC50 0.43 uM.
Additionally, capability of gamma-radiation to augment the cytotoxic activity of
14, 16 and 20 was studied and showed a dramatic increase in the cell killing
effect at lower concentrations after irradiation. Docking was used to investigate
the possible binding modes of compounds 14, 16 and 20 inside the active site of
CDK2 enzyme.
PMID- 29966875
TI - Mitigative role of garlic and vitamin E against cytotoxic, genotoxic, and
apoptotic effects of lead acetate and mercury chloride on WI-38 cells.
AB - BACKGROUND: Lead acetate (Led) and mercury chloride (Mer) represent important
ecological and public health concerns due to their hazardous toxicities.
Naturally found products play a vital role in chemopreventive agent innovation.
The current study aimed to assess the modifying effect of garlic (Gar) and/or
vitamin E (Vit E) against the half-maximal inhibitory concentration (IC50) Led
and/or Mer-induced cytotoxic, genotoxic and apoptotic effects. METHODS: Human
lung cells (WI-38) were pretreated with Gar and/or Vit E for 24h and then treated
with Led and/or Mer either alone or with their combination for 24h. Cytotoxicity
of Led and Mer and the viability of Gar and Vit E were assessed using MTT assay.
The alkaline comet assay was used to assess DNA damage, whereas QRT-PCR was
performed to evaluate p53, Bax, and Bcl2 mRNA-expression. RESULTS: The results of
this study showed that IC50 of Led was (732.72MUg/mL) and for Mer was
(885.83MUg/mL), while cell viability effective dose for Gar was (300MUg/mL) and
for Vit E was (26,800MUg/mL). Treating cells with the IC50-concentration of Led
or Mer or their combination using half IC50 of both of them induced severe DNA
damage. Bax-expression was increased, while p53 and Bcl2-expressions were
decreased. Pretreatment of cells with Gar and/or Vit E ameliorated the previous
alternations. CONCLUSIONS: Led and Mer can induce oxidative stress and change the
expressions of apoptosis-related proteins in WI-38 cells. Gar and Vit E may be
promising protective candidate agent against the toxic effect of heavy metals.
PMID- 29966876
TI - The association between whole blood concentrations of heavy metals in pregnant
women and premature births: The Japan Environment and Children's Study (JECS).
AB - BACKGROUND: Heavy metals are widely distributed in the environment. Recent
reports have demonstrated the risk of preterm birth following heavy metal
exposure. Preterm births are classified as early and late, depending on the
duration of pregnancy, and are associated with increased risk of congenital
illnesses such as heart failure, asthma, etc. Particularly, early preterm births
carry a higher risk of mortality; however, the differential effects of heavy
metal exposure on early and late preterm births are unknown. OBJECTIVES: To
analyze the association between maternal whole blood concentrations of heavy
metals, such as cadmium (Cd), lead (Pb), mercury (Hg), selenium (Se), and
manganese (Mn) that are common toxicants in Japan, and early and late preterm
births. METHODS: The data of 14,847 pregnant women who were participants of the
Japan Environment and Children's Study were used. Data of the self-questionnaire
pertaining to the first trimester (T1), second/third trimester (T2), and medical
records after delivery were analyzed. We divided preterm birth into two groups:
early preterm (22 to < 34 weeks) and late preterm (34 to < 37 weeks). Maternal
blood samples for measuring heavy metal concentrations were collected in T2
(pregnancy weeks: 14-39). The participants were classified into four quartiles
(Q1-Q4) according to increasing heavy metal levels. RESULTS: The rate of preterm
birth was 4.5%. After controlling for confounding factors, such as age, pre
pregnancy body mass index, smoking, partner's smoking, drinking habits,
gravidity, parity, number of cesarean deliveries, uterine infections, household
income, educational levels, and sex of infant, Cd levels were found, by
multivariable logistic regression analysis, to be significantly associated with
early preterm birth (p = 0.002), with odds ratio for early preterm birth of 1.91
(95% confidence interval: 1.12-3.27, P = 0.018) in subjects of Q4 compared with
in subjects with term birth (? 37 weeks). CONCLUSION: Maternal blood Cd levels
during pregnancy are positively associated with the risk of early preterm birth
among Japanese women. Identification of the main source of maternal Cd exposure
may contribute to the prevention of early preterm births and health maintenance
of mothers and their infants in the future.
PMID- 29966877
TI - Cross sectional association of arsenic and seroprevalence of hepatitis B
infection in the United States (NHANES 2003-2014).
AB - BACKGROUND: Arsenic alters immunological parameters including antibody formation
and antigen-driven T-cell proliferation. OBJECTIVE: We evaluated the cross
sectional relationship between urinary arsenic and the seroprevalence of
hepatitis B (HBV) infection in the United States using data from six pooled
cycles of the National Health and Nutrition Examination Survey (2003-2014, N =
12,447). METHODS: Using serological data, participants were classified as
susceptible, immune due to vaccination, or immune due to past natural infection.
We used multinomial logistic regression to evaluate the association between
urinary DMA and HBV classification. A sensitivity analysis using total urinary
arsenic (TUA) was also conducted. Both DMA and TUA were adjusted for
arsenobetaine using a residual regression method RESULTS: A 1-unit increase in
the natural logarithm (ln) of DMA was associated with 40% greater adjusted odds
of having immunity due to natural infection compared to being susceptible (Odds
Ratio [aOR]: 1.40, 95% Confidence Intervals [CI] 1.15, 1.69), 65% greater odds of
having immunity due to a natural infection (aOR: 1.65, 95% CI: 1.34, 2.04) and
18% greater odds of being susceptible (aOR: 1.18, 95% CI: 1.05, 1.33) compared to
being immune due to vaccination after adjusting for creatinine, age, sex, race,
income, country of birth, BMI, survey cycle, serum cotinine, recent seafood
intake, and self-reported HBV immunization status. CONCLUSION: In the U.S.
general public, higher urinary arsenic levels were associated with a greater odds
of having a serological classification consistent with a past natural hepatitis B
infection after adjusting for other risk factors. Additionally, higher urinary
arsenic levels were linked to a greater odds of not receiving hepatitis B
vaccinations. Given the cross-sectional nature of this analysis, more research is
needed to test the hypothesis that environmentally relevant exposure to arsenic
modulates host susceptibility to hepatitis B virus.
PMID- 29966878
TI - Impact of meteorological factors on mumps and potential effect modifiers: An
analysis of 10 cities in Guangxi, Southern China.
AB - BACKGROUND: In the current context of global climate change, understanding the
impact of climate on respiratory infectious diseases such as mumps and the
potential modified factors is crucial, especially in developing countries.
However, research on the climate-related incidence of mumps is rare, inconsistent
and mainly limited to a single city or region. METHODS: Daily mumps cases and
meteorological variables of 10 cities in Guangxi, Southern China were collected
for 2005-2017. Two-stage analyses were performed to assess the relationship
between meteorological factors and mumps incidence during two time-periods: 2005
2012 and 2013-2017, separately. First, a Poisson regression model that allows
over-dispersion was used to estimate the city-specific climate-related morbidity
after controlling for temporal trends, day of week, and national statutory
holidays. Then, we used a multivariate meta-analytical model to pool the city
specific effect estimates and conducted subgroup analyses. Multivariate meta
regression was applied to detect potential effect modifiers. RESULTS: Non-linear
relationships were observed among mean temperature, wind speed, and mumps
incidence in 2005-2012. The impact of high temperature on mumps incidence was
short and rapid, whereas the impact of low temperature was long and slow. The
total cumulative relative risk (RR) associated with hot temperature was 1.18 [95%
Confidence Interval (CI): 0.93, 1.48], which was calculated by comparing the
incidence of mumps above the 90th percentile of temperature with its incidence at
the median temperature at lag of 0-30 days. Meanwhile, the RR associated with
cold temperature was calculated to be 1.50 (95% CI: 1.08, 2.10) by comparing the
incidence of mumps below the 10th percentile of temperature with its incidence at
the median temperature. Similarly, the RRs associated with windless and windy
conditions for the total population were 1.23 (95% CI: 1.04, 1.46) and 0.83 (95%
CI: 0.67, 1.02), respectively. Effects based on extreme temperature and wind
speed conditions were more prominent in males than in females. Compared with
children and adults, adolescents (5-14 years old) were more sensitive to extreme
weather conditions. Geographical latitude, Population density, GDP per capita,
Number of health institutions, Highly educated population and Inoculation rate
were considered the most likely associated modifiers. In addition, the
correlation between meteorological factors and the incidence of mumps and
modification of socioeconomic factors after 2013 showed similar curves compared
with results in 2005-2012, but the cumulative effect was not statistically
significant. CONCLUSIONS: Meteorological factors, such as temperature and wind
speed, exert a significant impact on the incidence of mumps. The relationship
varies depending on gender and age. Socioeconomic factors such as vaccination,
GDP, geographical latitude, etc. may substantially affect the weather-related
mumps incidence.
PMID- 29966879
TI - A mixed methods sequential explanatory study of the psychosocial factors that
impact on midwives' confidence to provide bereavement support to parents who have
experienced a perinatal loss.
AB - BACKGROUND: Perinatal bereavement is traumatic for many parents. Not only is the
experience itself emotionally painful, the impact on their lives is made more
difficult if midwives are unable to provide appropriate care to the parents. AIM
OF THE STUDY: To explore within an Irish context, the psychosocial factors that
impact on midwives' confidence to provide bereavement support to parents who have
experienced a perinatal loss. DESIGN: A mixed methods sequential explanatory
design was used to complete this two-phased study from August 2013 to July 2014.
Ethical approval was granted from Ethics Committees of three maternity hospitals
and a University in Ireland. The recruitment process for the survey occurred in
August 2013 and July 2014 for the focus groups. METHODS: A series of univariate
and multivariate analysis were used to analyze the quantitative data using IBM
Statistical Package for the Social Sciences (SPSS; version 20). The qualitative
data were analyzed using qualitative content analysis. Steps were taken to ensure
data validity and reliability. RESULTS: The overall meta-inference of this study
is that the majority of the midwives did not have adequate levels of confidence
to provide bereavement support to grieving parents. The psychosocial factors that
impact on midwives' confidence were identified as the midwives' awareness of the
needs of bereaved parents, their own inner strength and the organizational
support they received at their place of work. CONCLUSION: Improving midwives'
bereavement support knowledge and skills is essential for promoting their
confidence. Midwives also need adequate emotional and practical support from
their organizations.
PMID- 29966880
TI - Early labour experience questionnaire: Psychometric testing and women's
experiences in a Swedish setting.
AB - OBJECTIVE: (a) to psychometrically test the Early Labour Experience Questionnaire
(ELEQ) among both primi- and multiparous women giving birth in a Swedish setting,
and (b) to describe and compare their experiences during early labour in relation
to background characteristics. DESIGN: a cross-sectional study. SETTING: a county
in Sweden. PARTICIPANTS: primi- and multiparous women with a spontaneous onset of
labour after gestational week 37 + 0. In total, n = 1193 women were invited, and
n = 754 responded the questionnaire, with a final total of n = 344 primi and n =
410 multiparous women. METHODS: the ELEQ was translated with cross-cultural
adaptation. The validity was determined using exploratory factor analysis with
principal axis factoring analyses. Reliability was estimated from the internal
consistency using Cronbach's alpha. The relationship between the questionnaire
and the demographic characteristics of the participating women were analysed
using ANOVA and t-test. FINDINGS: an explorative factor analysis showed a three
factor solution for primiparas women (SWE-ELEQ-PP) consist of 23 items and a
stable factor structure that explained 49.2% of the total variance with
sufficient reliability coefficients (0.81-0.86). A four-factor solution for
multiparous women (SWE-ELEQ-MP) consist of 22 items, with 52.62% of the total
variance explained and with adequate internal consistency reliability
coefficients (0.77-0.86) for three factors and relatively low stability (0.62)
for the fourth factor with two items. Primiparous women scored significantly
higher on items about feeling confused, and significantly lower on some items
measuring emotional wellbeing and perceptions of midwifery care compared to
multiparous women. Primiparous women with longer early labour (>18 h), scored
significantly lower on the perceptions of midwifery care. Primi- and multiparous
women who were dissatisfied with their telephone conversation or with not being
admitted during early labour, scored significantly lower on emotional wellbeing,
higher regarding emotional distress, and significantly lower about perceptions of
midwifery care. KEY CONCLUSIONS: the SWE-ELEQ-PP and SWE-ELEQ-MP are considered
valid questionnaires for use in a Swedish setting. Differences exist between
parity and the factor structure and experiences in early labour vary. Women less
content with early labour management decisions rated perceived midwifery care
lower regardless of parity. IMPLICATION FOR PRACTICE: the questionnaire can be
used to evaluate early labour care in a Swedish setting. The result suggests that
differences according to parity exist and should be addressed when managing early
labour care and a more individualised approach requires considerations.
PMID- 29966881
TI - Critical thinking dispositions in undergraduate nursing students: A case study
approach.
AB - BACKGROUND: The transition of nurse education to the higher education sector in
Ireland in autumn 2002 led to the development of a new curriculum for
undergraduate nursing with critical thinking as an expected outcome. OBJECTIVES:
To investigate critical thinking dispositions and the difference between first
and third year nursing students. DESIGN: A single embedded case study approach
incorporating a cross-sectional design. SETTING: Two similar university sites
providing a new four year undergraduate honours degree programme in nursing.
PARTICIPANTS: A cohort of first (n = 237) and a cohort of third year (n = 215)
undergraduate nursing students. METHODS: Critical thinking provided the main case
for this case study. The Delphi conceptualisation of critical thinking
underpinned the study and critical thinking dispositions were measured using the
California Critical Thinking Disposition Inventory. The data were analysed using
descriptive statistics and an independent samples t-test was used to determine
differences between the first and third year nursing students. RESULTS: First
year nursing students scored strong while third year students scored weak in
overall critical thinking disposition. Both first and third year nursing students
revealed a strong score for inquisitiveness, open-minded, analyticity and
maturity dispositions. They revealed weak scores for self-confidence,
systematicity and truth-seeking dispositions. Inquisitiveness was the strongest
while truth-seeking was the weakest disposition for both cohorts. Neither cohort
reached the higher positive scores indicative of consistent endorsement of higher
level thinking. CONCLUSIONS: Nurse educators need to develop their knowledge of
critical thinking dispositions and foster these attributes throughout the pre
registration nursing degree programme. Clinically based scenarios which challenge
nursing students and invoke questioning contribute to critical thinking
development. Statutory bodies responsible for nurse education and nurse educators
must continue to encourage critical thinking.
PMID- 29966882
TI - Nursing students' discourses on gender-based violence and their training for a
comprehensive healthcare response: A qualitative study.
AB - BACKGROUND: Gender-based violence is a worldwide major public health issue with
detrimental effects on the health of women. Nurses can play an essential role in
its identification, management and prevention. Specific training is essential to
be able to successfully address gender-based violence and accordingly, has been
incorporated into many university's training programmes for nurses and other
health care professionals. Research aimed at exploring attitudes and perceptions
of gender-based violence in undergraduate student nurses following these new
training programmes is scarce. OBJECTIVE: The aim of this qualitative study was
to explore third- and fourth-year nursing students' perceptions and attitudes
toward gender-based violence. DESIGN: A focus groups based qualitative study.
SETTING: A public University in Spain. PARTICIPANTS: Purposive sample of 42
nursing students who joined 7 focus groups. METHODS: Focus groups discussions
following a semi-structured interview guide. Discussions were transcribed and
analysed following critical discourse analysis to identify interpretative
repertoires. RESULTS: From the analysis, three interpretative repertoires
emerged. The first, 'Gender-based violence is something serious', reflected
participants' acknowledgment of the social relevance of this type of violence.
The second interpretative repertoire, 'Men are defenceless!', related to the
perception that national legislation on gender-based violence was discriminatory
to men and the perception of a lack of social sensitisation toward intimate
partner violence against men. The last one, 'Trained to address gender-based
violence but still unprepared' encompassed participants' confidence in their
ability to identify gender-based violence but uncertainty as to how to respond to
gender-based violence exposed women in terms of professional practice.
CONCLUSIONS: Participants perceived that training has increased their knowledge
and self-confidence in identifying cases. However, training should strongly
challenge widespread myths about gender-based violence that could negatively
affect their performance as nurses.
PMID- 29966883
TI - Midwifery students' experiences of their clinical internship: A qualitative
descriptive study.
AB - BACKGROUND: Globally the safety of mothers and babies is fundamental in maternity
care. Central to ensuring this safety is appropriate preparation of midwifery
students' to ensure graduates are equipped to assume the responsibilities of
delivering safe and effective maternity care. In preparation for autonomous
practice Irish midwifery students' undertake a 36 week internship in the final
year of the BSc Midwifery programme. Within this paid internship midwifery
students' have the opportunity to develop professional behaviours, consolidate
knowledge and learn necessary skills to fulfil the role of midwife under the
supervision of registered midwives. OBJECTIVE: To explore midwifery students'
experiences of the internship period. DESIGN AND METHOD: A descriptive
qualitative study using focus groups with ethical approval. SETTING AND
PARTICIPANTS: BSc Midwifery students' in the final year of their programme (n =
17) in an Irish University were invited to participate in a focus group interview
midway through their internship. All participants (n = 13) had experience of
working in two sites used for internship at the time of data collection. RESULTS:
Key findings include the importance of the internship period in consolidating
clinical skills and building confidence and competence for midwifery practice.
Midwifery students' experience considerable stress during the internship period.
Demands identified as stressors include providing care in increasingly complex
clinical areas, meeting academic deadlines and maintaining a work life balance.
Negative interpersonal experiences and dismissive attitudes to reflection on
practice were barriers to learning. Midwifery students' articulated the
importance of learning through doing, a supportive learning culture and
philosophy in the unit, protected time for reflection and being included and
valued as part of the midwifery team. CONCLUSIONS: The benefits and challenges
associated with internship in midwifery are apparent, particularly when students'
are contending with two geographically distant sites. Support mechanisms and
suggestions for improvements are considered.
PMID- 29966884
TI - Interprofessional education (IPE) in clinical practice for pre-registration
nursing students: A structured literature review.
AB - OBJECTIVES: To explore the experiences of nursing students after clinical IPE
activities through a review of contemporary literature then use the context of
nursing programmes in Singapore to consider the transferability of the findings.
DESIGN: Structured literature review. DATA SOURCES: A search of international
qualitative literature no older than five years and published in English was
conducted on CINAHL, Embase, Medline and Pubmed. REVIEW METHODS: A systematic and
structured approach was guided by Cooper's five-step approach to review the
literature. The Critical Appraisal Skills Programme qualitative checklist and the
Appraisal of Guidelines Research & Evaluation reporting checklist were used to
critically appraise literature in this review. RESULTS: 13 papers were included
for qualitative synthesis. The literature most commonly reported that students
had a better understanding of professional roles, improved communication and
teamwork. In contrast, the most commonly reported negative experience involved
some examples of disparity within the team. CONCLUSION: Overall findings show
that positive student experiences outweigh negative ones. Nursing programmes
might be able to reap similar outcomes subject to contextual and cultural
differences. However, further research is recommended before IPE in clinical
practice is implemented in current nursing programmes in the local setting.
PMID- 29966885
TI - Maternal filicide: A case series from a medico-legal psychiatry unit in India.
AB - Maternal filicide has occurred throughout history and carries along with it, a
host of paradoxical and complex clinical, legal and social dimensions. We present
findings from a case series of four women inpatients, who were undergoing trials
for filicide. All women reported severe marital discord and poor social support.
Three had severe depressive episodes before and during the time of the alleged
crime. The motive for the alleged act was 'altruistic' in three of them. Early
identification of psychiatric illness and risk assessment may help in early
intervention and protect the mother and child.
PMID- 29966886
TI - Burden of common mental disorders among pregnant women: A systematic review.
AB - INTRODUCTION: Common mental disorders (CMDs) including depressive and anxiety
disorders during antenatal period is reported to affect both mother and child
health outcomes. There is scarce evidence about burden of CMDs during pregnancy
from Lower and Middle Income Countries. OBJECTIVE: To review the evidence about
the burden of common mental disorders among pregnant women METHODS: Major
databases were searched systematically for English language studies on prevalence
of CMDs. Quality assessment of studies was done with the modified version of
Newcastle-Ottawa Scale for non-analytical studies. RESULTS: Twenty three studies
were included in the review. The prevalence of CMDs among pregnant women ranged
from 1%-37%. Depression was more commonly studied (ranged from 1%-30%).
Prevalence of GAD ranged from 1%-26%. Factors commonly associated with CMDs were
lower SES, intimate partner violence, history of previous episode of CMDs,
history of mental illness in family and unmarried status. Effect of CMDs on child
health outcome was also detected. CONCLUSION: CMDs are common during pregnancy
with varying prevalence depending on various settings and scales used.
PMID- 29966887
TI - Primary care physicians' perceived barriers on the management of depression in
China primary care settings.
AB - BACKGROUND: Chinese patients with depression have limited access to mental health
specialty care because of myriad barriers at different levels. Recently, there
has been increased interest in targeting primary care settings for managing
depression, because most depressed individuals visit their primary care
physicians (PCPs) during the course of their depressive episodes. The present
study examined PCPs' perceived barriers on the management of depression. METHODS:
A total of 295 PCPs completed a 36-item survey by mail. The survey questions
included demographics, years in primary care, mental health training experience,
and perceived barriers regarding the management of depression in their clinical
and current practices. Chi-square and t-test analyses were used to compare the
difference of demographic variables between the two districts. For the correlates
of PCPs' clinical practices and their perceived barriers, logistic regression
models were used. RESULTS: At the practice level, lack of access to mental health
specialists (37.8%) was the most commonly reported barrier and at patients'
level, reluctance toward diagnosis of depression (34.6%) was the high barrier.
Results have indicated that most PCPs (69.2%) felt comfortable discussing
psychological issues with patients. Mental health training is significantly
related to PCPs' clinical practice. When PCPs perceived moderate to high-level
practice level barriers, prescription and referral were mostly preferred.
CONCLUSION: PCPs in China perceived some barriers in the management of
depression, but they were open to modifications and enhancement of their skills
related to managing depression.
PMID- 29966888
TI - Olanzapine associated palpebral edema: An uncommon adverse effect of a commonly
prescribed drug.
PMID- 29966889
TI - The effectiveness of acupuncture on HPA functional in depressed patients under
methadone maintenance treatment, a randomized double-blind sham-controlled trial.
PMID- 29966890
TI - Isolated vocal akathisia-Does it exist?
AB - An 81 years old Jewish-Iranian lady, with a psychiatric history of postpartum
depression in her twenties and a previous hospitalization due to a depressive
episode accompanied by suicidal thoughts and a history of hearing loss and COPD,
was hospitalized in the psychogeriatric department of our Mental Health Center
due to repetitive incoherent sounds she was uttering for the past month, which
increased in intensity and caused suicidal thoughts.
PMID- 29966891
TI - The Brief Negative Symptom Scale: Validation in a multicenter Brazilian study.
AB - BACKGROUND: Negative symptoms are a core feature of schizophrenia. The Brief
Negative Symptom Scale (BNSS) is a scale developed to measure negative symptoms
in schizophrenia. METHODS: The present study aimed to examine the construct
validity of BNSS, by using convergent and divergent validities as well as factor
analysis, in a Brazilian sample of 111 outpatients diagnosed with schizophrenia
by DSM-5. Patients were evaluated by the Brazilian version of the BNSS and
positive and negative subscales of the Positive and Negative Syndrome Scale
(PANSS). RESULTS: Assessment of patients by both instruments revealed an
excellent internal consistency (Cronbach's alpha = 0.938) or inter-rater
reliability (ICC = 0.92), as well as a strong correlation between BNSS and Marder
negative PANSS (r = 0.866) and a weak correlation of the instrument with the
positive PANSS (r = 0.292), thus characterizing convergent and discriminant
validities, respectively. The exploratory factor analysis identified two distinct
factors, namely, motivation/pleasure and emotional expressivity, accounting for
68.63% of the total variance. CONCLUSION: The study shows that the Brazilian
version of the BNSS has adequate psychometric properties and is a reliable
instrument for the assessment of negative symptoms in schizophrenia, either for
clinical practice or research.
PMID- 29966892
TI - Determination of vertical ionization potential of nitroso-benzoimidazothiazole
using charge transfer interaction with a series of acceptors.
AB - This is the first report of UV-Vis spectral investigations of electron donor
acceptor complexes of bio active 3-Nitroso-2-phenylbenzo[d]imidazo[2,1-b]thiazole
(BIT1) with chloranils, nitrobenzenes and fullerenes in DMSO medium. Well defined
charge transfer (CT) absorption bands in the visible region have been sited.
Oscillator strengths, transition dipole and resonance energies of the CT
complexes have been estimated. Utilizing Mulliken's equation vertical ionization
potential of BIT1 has been determined. A possible mechanism for the interaction
between electronic subsystems of chloranils, nitrobenzenes, [60]- and [70]
fullerenes with this benzoimidazothiazole compound (BIT1) have been discussed in
comparing the parameters like degree of charge transfer and binding constant in
polar DMSO. 1H NMR study helps to explain the mechanism well. Comparison of
complexes is done with DFT/PW1PW91/6-31G* optimized gas phase geometries and FMO
features of adducts.
PMID- 29966893
TI - Investigation of adsorption performance of graphene oxide/polyaniline reinforced
hollow fiber membrane for preconcentration of Ivermectin in some environmental
samples.
AB - Herein, the application of Graphene oxide-polyaniline (GO/PANI) in one of newly
hollow fiber based microextraction techniques so called (HF-S/LPME) was
investigated successfully. Graphene oxide-polyaniline (GO/PANI) nanocomposite was
generated via an amidation reaction in the presence of N, N'
dicyclohexylcarbodiimide (DCC), N-hydroxysuccinimide (NHS) and GO as starting
material. The solid sorbent dispersed in dihexyl ether was immersed and injected
into the lumen of hollow fiber. The results indicated that GO/PANI had a higher
adsorption efficiency for the Ivermectin in comparison with GO and GO-ethylen
diamine (GO/EDA). A Taguchi experimental design with an OAD16 (45) matrix was
employed to optimize the affecting parameters such as pH, stirring rate,
extraction time, salt addition and the volume of donor phase. Under the optimized
extraction conditions, the method showed a good linear dynamic range (0.1-5000.0
ppb) with a lower limit of detection (0.03 ppb) and excellent preconcentration
factor (PF = 219.88) respectively.
PMID- 29966894
TI - Pd/Pt metallacyclopropa[60]fullerene complexes bearing versatile phosphorous
ylide ligands; a comprehensive multi-spectroscopic, electrochemistry, theoretical
and catalytic studies.
AB - The synthesis of new Pd/Pt metallacyclopropa[60]fullerene complexes containing
unsymmetrical phosphorus ylides [Ph2P(CH2)nPPh2 = C(H)C(O)C6H4-p-OMe] (n = 1,
(Y1); n = 2, (Y2)) has been reported. The synthesized complexes exhibit different
structures, including two P,C- chelated [(eta2-C60)Pd(kappa2-Y1)] (1) and [(eta2
C60)Pt(kappa2-Y1)] (2) complexes and two P-coordinated [(eta2-C60)Pd(Y2)2] (3)
and [(eta2-C60)Pt(Y2)2] (4) complexes with chain structures. Characterization of
all compounds was performed by multi-neclear NMR spectroscopies (1H, 13C and 31P
NMR) and other conventional techniques such as IR, UV-Vis, SEM and cyclic
voltammetry (CV) analyses. In this regard, the presence of all characteristic
chemical shifts in the IR and NMR spectra proposed the formation of desired
products. Also, theoretical studies were used to investigate the nature of metal
ligands in all complexes. In addition, a comparison between the catalytic
activity of Pd complexes 1 and 3 was evaluated in the Suzuki-Miyaura reaction of
various aryl chlorides with phenylboronic acid, which revealed a meaningful
difference between the catalytic activity of complexes 1 and 3.
PMID- 29966895
TI - Undulation induced tuning of electron acceptance by edge-oxidized graphene oxide.
AB - Edge-oxidized graphene oxide (EOGO) nanosheets are good acceptors of electrons.
We have employed a suitably designed pyrene-tailed fluorescent probe to establish
that the electron acceptability of EOGO can be tuned by undulation of the GO
sheet. Comparison between EOGO and single-walled carbon nanotubes (SWCNT) on
electron acceptance from the probe molecule shows that the efficiency of pi-pi
stacking between pyrene and the graphene sheet plays the key role.
PMID- 29966896
TI - A paper platform for colorimetric determination of aluminum hydrochloride in
antiperspirant samples.
AB - A simple, fast, low-cost, portable, and eco-friendly method using a spot test on
a paper platform, together with diffuse reflectance spectroscopy, was developed
and validated for the quantification of aluminum hydrochloride, a potential
neurotoxic agent, in antiperspirant samples. The determination of aluminum
hydrochloride was performed at a wavelength of 615 nm, by measuring consumption
of the purple colorimetric reagent Alizarin S, due to reaction with aluminum. The
linear range was from 10.0 to 125.0 mg L-1 and could be described by the
equation: AR = 0.4479 - 0.002543 CAl (R = 0.999). The limits of detection (LOD)
and quantification (LOQ) were 3.06 and 10.2 mg L-1, respectively. The method was
specific, accurate, and repeatable, with relative standard deviation (RSD) <5.0%.
The recovery was between 92.2 and 103.4%. The method was successfully used for
the determination of aluminum hydrochloride in commercial antiperspirant samples,
revealing concentrations below the maximum permitted by current legislation.
PMID- 29966897
TI - A new method for hydroxyl radical detection by chemiluminescence of flue-cured
tobacco extracts.
AB - Chemiluminescence (CL) reactions usually take place in a severely restricted pH
regime, thereby confining their application in media at different pH. In this
paper, the CL behavior of tobacco-methanol extract (TME) was explored.
Surprisingly, TME exhibited CL behavior upon mixing with Fe2+/H2O2, HRP/H2O2 and
gold nanoparticles/H2O2 oxidation systems, i.e., in acidic, neutral and alkaline
solution respectively. Addition of different reactive oxygen species scavengers
verified that the hydroxyl radical (OH) triggers TME CL reactions. Then, the CL
behavior of TME was applied to determine OH in tetrachloro-1,4-benzoquinone
(TCBQ)/H2O2 system in acidic, neutral and alkaline solutions. CL intensity
correlated most strongly (R2 = 0.99) with TCBQ concentration, which was used as a
means to indirectly denote OH concentration. This implies that OH could be
determined by a TME CL method in a semi-quantitative way regardless of pH value.
Therefore, the TME CL method may be a promising method for OH determination in
various OH-generating systems.
PMID- 29966898
TI - Effects of carotenoids on the absorption and fluorescence spectral properties and
fluorescence quenching of Chlorophyll a.
AB - Fluorescence and absorption characteristics of Chlorophyll a (Chl-a) were
modulated by the carotenoids (Cars) with different numbers of conjugated carbon
carbon double bonds in solutions. The Chl-a absorption appears the redshift
phenomenon with the effective conjugated of Cars increasing. The absorption of
Chl-a and Cars are linearly dependent on intrinsic factors, namely effective
conjugate length and functional groups, and on environmental factors, such as the
polarizability of the solvent. Cars can be able to quench the Chl-a fluorescence
by producing the non-emitting exciplex intermediate. The effective conjugated
length of Cars is one of the reasons that effect the fluorescence quenching of
Chl-a. According to the Stern-Volmer plots, the Chl-a fluorescence quenching
should be predominantly dynamic rather than static.
PMID- 29966899
TI - Two-photon fluorescent probe with enhanced absorption cross section for relay
recognition of Zn2+/P2O74- and in vivo imaging.
AB - A novel multifunctional probe, L, based on triphenylamine o-hydroxyl Schiff base
was constructed for the sequential detection of Zn2+/P2O74-. Interestingly, probe
L also showed two-photon fluorescent "off-on" response to Zn2+ along with a large
effective two-photon absorption cross-section value of 240 GM at 720 nm, a low
cytotoxic and a moderate photostability, which made L a good candidate for two
photon fluorescence microscopy imaging and monitoring the fluctuation of
exogenous Zn2+.
PMID- 29966900
TI - Understanding the vibrational spectra of crystalline isoniazid: Raman, IR and INS
spectroscopy and solid-state DFT study.
AB - This work presents a comprehensive spectroscopic analysis of crystalline
isoniazid, one of the main drugs in tuberculosis chemotherapy, using a blend of
spectroscopic and computational methods. Mid- and far-infrared, Raman, and
inelastic neutron scattering spectroscopies, with contribution of isotopic
substitution are combined with discrete and periodic DFT quantum chemical
calculations. This combined approach successfully reproduces the whole spectral
range, allowing a sound assignment of all the vibrational bands. Previous
misassignments have been corrected and several spectral features of isoniazid
crystal are reported for the first time. Virtues and limitations of the
computational approach (periodic and discrete) are also discussed in light of the
present state-of-the-art in the field.
PMID- 29966901
TI - All that glitters is not gold: A non-destructive probing of Thanjavur painting by
Raman spectroscopy.
AB - In this work, we demonstrate the use of Raman spectroscopy in detecting the
presence of gold and semi-precious/precious gemstones in one of the classical
paintings of India namely the Thanjavur paintings which have been awarded the
Geographical Indication. We find through Raman spectroscopy that there are
paintings where fake gold is used in the place of original gold foils. This
result has been validated by carrying out the energy dispersive X-ray analysis
(EDX) which confirms the Raman spectroscopy findings. We propose Raman
spectroscopy as a diagnostic tool for detecting the presence of gold and thereby
to frame regulations for the Thanjavur painting market which would be of utmost
importance to the artisans as well as its connoisseurs.
PMID- 29966902
TI - Validated ion pair chromatographic method for simultaneous determination and in
vitro dissolution studies of indacaterol and glycopyrronium from inhaled capsule
dosage form.
AB - A rapid, and highly sensitive analytical method were developed for the
simultaneous determination of indacaterol maleate (IND) and glycopyrronium
bromide (GLY) in their inhaler capsules. Valid ion-pairing chromatographic (IPC)
method was performed for separation of GLY in presence of IND using C18 column
and mobile phase consisting of acetonitrile: acidified deionized water (60:40%
v/v) containing 0.02% sodium dodecyl sulfate (SDS) adjusted to pH 3.0 using OPA
(orthophosphoric acid) isocratically eluted at 2.0 mL/min. Quantitation was
achieved with UV detection at 210 nm. Cyproheptadine was used as an internal
standard. The retention times were 1.9 and 2.5 min for IND, and GLY,
respectively. For the IPC method, the calibration graphs were linear in the range
of 0.66-66.0 MUg/mL for IND and 0.3-30.0 MUg/mL for GLY. The proposed method are
rapid, reproducible (R.S.D. <2.0%) and achieves satisfactory resolution between
IND and GLY (resolution factor = 4.23). The mean recoveries of the analytes in
their inhaler capsule were satisfactory. It was applied successfully to in vitro
dissolution testing using Franz diffusion cell and extended to a content
uniformity test consistent with the United States Pharmacopoeia (USP) guidelines
and were found to be precise and accurate for the capsules studied with
acceptance value of 4.53 and 1.39 for IND and GLY, respectively.
PMID- 29966903
TI - Blood mononuclear cells as speculum of emotional stress analyzed by synchrotron
infrared spectroscopy and a nootropic drug.
AB - Chronic psychological stress is an important public health issue which generates
behavioral changes, anxiety, immunosuppression and oxidative damage. Piracetam is
a cognitive enhancer, at cellular level it protects from oxidative stress. The
aim of this study was to evaluate the effect of psychological stress and of
piracetam on circulating mononuclear cells by analyzing the biochemical spectrome
using Synchrotron Radiation Fourier Transform Infrared Microspectroscopy (SR
MUFTIR). Rats were exposed for five days to a stressor (cat odor) under oral
administration of piracetam (600 mg/kg). SR-MUFTIR analysis showed a decrease in
bands associated to the lipids region (2852 cm-1, 2923 cm-1 and 2962 cm-1) and an
increase absorption of the amide I band (1654 cm-1) under stress conditions. The
principal component analysis showed increase oxidation of lipids (decrease of
3010 cm-1, 2923 cm-1 and 2852 cm-1 bands) as well as proteins denaturation
(increase of 1610 cm-1 and 1690 cm-1 bands) under stress. Piracetam provided
protection to polyunsaturated lipids (p <= 0.001) and lipids/proteins ratio (p <=
0.001). Behaviorally, this drug diminished fear and anxiety in stressed animals
by the plus maze test (p <= 0.002). However, this drug induced oxidative stress
in mononuclear cells from unstressed animals and altered their behavior.
PMID- 29966904
TI - Role of surface charge on the interaction between carbon nanodots and human serum
albumin.
AB - Carbon nanodots (Cdots) have aroused widespread concerns in the field of
biomedical applications. In order to achieve better implications of behavior of
Cdots in the biological environment, an array of spectroscopic, electrochemical
and calorimetric techniques were performed to study the interaction of Cdots
possessing different charges with human serum albumin (HSA) in physiological
condition. Two polymer, polyethylene glycol (PEG) and polyetherimide (PEI), were
applied to passivate the bare Cdots to achieve the Cdots with different surface
charge, namely negatively charged PEG Cdots and positively charged PEI Cdots. The
fluorescence of HSA was obviously quenched by both Cdots in a charge-independent
behavior through a dynamic collision mechanism. Moreover, the association
affinity of PEG Cdots or PEI Cdots bound to HSA was very close to each other. In
addition, PEG Cdots with diverse content exhibited little effects on the
secondary structure of HSA while only high content of PEI Cdots induced obvious
conformation perturbation of HSA. The electrostatic forces dominate the
association between HSA and PEI Cdots while the association of PEG Cdots to HSA
is initiated by hydrophobic and van der Waals forces. Furthermore, the results of
isothermal titration calorimetry revealed that both the interaction was driven by
favorable entropy and enthalpy, which confirmed that these association processes
are thermodynamically spontaneous. Finally, the sites marker competitive
experiment showed that the association sites of Cdots with HSA exhibit a charge
dependent manner, namely PEG Cdots effectively occupy the site I of HSA while the
association sites of PEI Cdots are mainly located in site II.
PMID- 29966905
TI - Mixed micellar system stabilized with saponins for oral delivery of vitamin K.
AB - Poorly soluble vitamin K cannot be absorbed by patients suffering from
cholestasis due to extremely low level of bile salts in the intestine. A
formulation of vitamin K including glycocholic acid (i.e. Konakion(r) MM), does
not increase bioavailability because it is unstable due to protonation of
glycocholic acid at gastric pH. To develop a stable formulation, saponins were
introduced as neutral surfactants to (partly) replace glycocholic acid.
Experimental design was made to investigate the effect of the composition on
particle size at neutral pH and upon acidification at pH 1.5. Two formulations
that were within the optimized composition window were loaded with vitamin K and
those showed superior stability at low pH as compared to Konakion(r) MM: sizes
were between 43 and 46 nm at pH 7.3 and between 46 and 58 nm after 1 h incubation
at pH 1.5, respectively, but large aggregates were formed at pH 1.5 in presence
of Konakion(r) MM. Micelles were cytocompatible with Caco-2 cells at
concentration of surfactants (saponins and glycocholic acid) up to 0.15 mg/ml.
Uptake of vitamin K by Caco-2 cells was 4.2-4.9 nmol/mg protein for saponins
containing formulations and 7.1 nmol/mg protein for Konakion(r) MM. This,
together with the superior stability at low pH, makes saponins-containing mixed
micelles promising oral formulations for vitamin K.
PMID- 29966906
TI - Multi-functional nanocarriers based on iron oxide nanoparticles conjugated with
doxorubicin, poly(ethylene glycol) and folic acid as theranostics for cancer
therapy.
AB - Multi-functional nanocarriers based on iron oxide nanoparticles (IONPs)
conjugated with doxorubicin (DOX), poly(ethylene glycol) (PEG), and folic acid
(FA) (IO-MMA-DOX-PEG-OCH3/FA) were prepared as theranostics for cancer therapy.
Using mono-methyl adipate (MMA) as a linker, the anticancer drug, DOX, was
conjugated on the surface of IONPs by acid-cleavable hydrazone bond. The average
size of the IO-MMA-DOX-PEG-OCH3/FA nanocarriers was determined as 14 and 40 nm by
TEM and DLS, respectively. The saturation magnetization (Ms) and transverse
relaxivity (r2) value of IO-MMA-DOX-PEG-OCH3/FA nanocarriers were calculated as
28.62 Am2/kg and 133 mM-1s-1, respectively. The rate and amount of DOX released
from the IO-MMA-DOX-PEG-OCH3/FA nanocarriers were higher at acidic medium (pH
5.6) than that at alkaline medium (pH 7.4) due to the presence of hydrazone bond
between the DOX and IONPs. The IO-MMA-DOX-PEG-OCH3/FA nanocarriers showed the
higher cellular uptake than FA-free nanocarriers due to the folate-receptor
mediated endocytosis, thereby presenting an enhanced cytotoxicity against folate
receptor-positive HeLa cells through apoptosis. The results confirmed that the IO
MMA-DOX-PEG-OCH3/FA nanocarriers could be promising for cancer therapy with the
improved drug loading, tumor-targeted controlled drug release and MRI abilities.
PMID- 29966907
TI - Motion analysis evaluation of adolescent athletes during dual-task walking
following a concussion: A multicenter study.
AB - BACKGROUND: Research suggests that dynamic balance in adolescents is compromised
following concussion and may worsen if patients return to sport (RTS) too soon.
Understanding if there are ongoing dynamic balance deficits in adolescents at the
time of RTS clearance would determine if more complex motor tasks are necessary
to facilitate safe RTS decisions. RESEARCH QUESTION: The purpose of this study
was to determine if there were remaining dynamic balance deficits in concussed
adolescents at the time of clearance for RTS. METHODS: Sixteen concussed
adolescent athletes (age 14.6 +/- 1.8 years; 9 males; 57 +/- 46 days post injury)
performed a simple walking task as well as two split attention gait tasks
(reciting months backwards and audio Stroop). The center of mass (COM) movement
and walking velocity during these tasks was compared to a control group of 15
healthy non-concussed adolescent athletes (age 13.8 +/- 1.4 years; 9 male).
RESULTS: The results indicated that there were no statistically significant
differences between the two groups for any of the tasks. Height-normalized
walking speed did not differ between groups during walking alone (control: 0.757
+/- 0.119, concussed: 0.739 +/- 0.108, p = 0.34), with the recitation task
(control: 0.555 +/- 0.095, concussed: 0.557 +/- 0.143, p = 0.72), or with the
Stroop task (control: 0.589 +/- 0.129, concussed: 0.567 +/- 0.141, p = 0.43).
Similarly, height-normalized medial-lateral COM displacement did not differ
between groups during walking alone (control: 0.027 +/- 0.007, concussed: 0.028
+/- 0.007, p = 0.98, with the recitation task (control: 0.037 +/- 0.012,
concussed: 0.0.037 +/- 0.016, p = 0.82), or with the Stroop task (control: 0.032
+/- 0.014, concussed: 0.033 +/- 0.009, p = 0.891). SIGNIFICANCE: These findings
indicate that the patients were returned to sport when their dynamic balance was
similar to controls suggesting that this cohort had recovered from their
concussion. However, large variability in dynamic balance measures in both the
patient and control groups may reflect ongoing neuromuscular development and
requires further exploration.
PMID- 29966908
TI - Estimation of muscle activation during different walking speeds with two
mathematical approaches compared to surface EMG.
AB - BACKGROUND: Muscle force estimation could improve clinical gait analysis by
enhancing insight into causes of impairments and informing targeted treatments.
However, it is not currently standard practice to use muscle force models to
augment clinical gait analysis, partly, because robust validations of estimated
muscle activations, underpinning force modelling processes, against recorded
electromyography (EMG) are lacking. RESEARCH QUESTION: Therefore, in order to
facilitate future clinical use, this study sought to validate estimated lower
limb muscle activation using two mathematical models (static optimisation SO,
computed muscle control CMC) against recorded muscle activations of ten healthy
participants. METHODS: Participants walked at five speeds. Visual agreement in
activation onset and offset as well as linear correlation (r) and mean absolute
error (MAE) between models and EMG were evaluated. RESULTS: MAE between measured
and recorded activations were variable across speeds (SO vs EMG 15-68%, CMC vs
EMG 13-69%). Slower speeds resulted in smaller deviations (mean MAE < 30%) than
faster speeds. Correlation was high (r > 0.5) for only 11/40 (CMC) and 6/40 (SO)
conditions (muscles X speeds) compared to EMG. SIGNIFICANCE: Modelling approaches
do not yet show sufficient consistency of agreement between estimated and
recorded muscle activation to support recommending immediate clinical adoption of
muscle force modelling. This may be because assumptions underlying muscle
activation estimations (e.g. muscles' anatomy and maximum voluntary contraction)
are not yet sufficiently individualizable. Future research needs to find timely
and cost efficient ways to scale musculoskeletal models for better
individualisation to facilitate future clinical implementation.
PMID- 29966909
TI - Life history traits and genotoxic effects on Daphnia magna exposed to waterborne
uranium and to a uranium mine effluent - A transgenerational study.
AB - Assessing the impact of uranium mining industry on aquatic ecosystems near mining
areas is critical to ensure the long-term health and sustainability of ecosystem
services. As so, a transgenerational study with Daphnia magna has been conducted
to perceive to what extent intermittent discharges of uranium mine effluents into
watercourses may impact the DNA integrity and life history traits of cladocerans.
Organisms were exposed for 48 h to a 2% dilution of an uranium mine effluent
(UME) and to a corresponding dose of waterborne uranium (WU) that, according to
our preliminary studies, induces significant DNA damage in daphnids. After
exposure, organisms were transferred to clean medium, where three successive
generations were monitored for genotoxicity and other effects at the individual
and population level. Despite some differences between WU and UME data, our
results revealed that the negative impacts of the short-term exposure gradually
disappeared after placing the organisms in clean medium. These results suggest
that, under intermittent stress, daphnids are able to recover, since after the
3rd brood release, DNA damage (measured as DNA strand breaks) is no longer
observed and has no significant impact on the detectable life traits of
offspring. Although our results indicate that populations of D. magna are not
affected by intermittent and highly diluted discharges from uranium mining,
aquatic systems under this kind of pressure should not be seen as hazardous-free.
Future studies in this field are recommended and these should consider
radionuclides in the water column, their accumulation in the sediments and also
multiple life stages.
PMID- 29966910
TI - Developmental and latent effects of diluted bitumen exposure on early life stages
of sockeye salmon (Oncorhynchus nerka).
AB - The early life stages of Pacific salmon are at risk of environmental exposure to
diluted bitumen (dilbit) as Canada's oil sands industry continues to expand. The
toxicity and latent effects of dilbit exposure were assessed in sockeye salmon
(Oncorhynchus nerka) exposed to water-soluble fractions of dilbit (WSFd) from
fertilization to the swim-up stage, and then reared in clean water for 8 months.
Mortality was significantly higher in WSFd-exposed embryos, with cumulative
mortality up to 4.6-fold higher in exposed relative to unexposed embryos. The
sublethal effects of WSFd exposure included transcriptional up-regulation of
cyp1a, a concentration-dependent delay in the onset and progression of hatching,
as well as increased prevalence of developmental deformities at total polycyclic
aromatic hydrocarbon (TPAH) concentrations >=35 MUg L-1. Growth and body
composition were negatively affected by WSFd exposure, including a concentration
specific decrease in soluble protein concentration and increases in total body
lipid and triglyceride concentrations. Mortality continued during the first 2
months after transferring fish to clean water, reaching 53% in fish exposed to
100 MUg L-1 TPAH; but there was no latent impact on swimming performance, heart
mass, or heart morphology in surviving fish after 8 months. A latent effect of
WSFd exposure on brain morphology was observed, with fish exposed to 4 MUg L-1
TPAH having significantly larger brains compared to other treatment groups after
8 months in clean water. This study provides comprehensive data on the acute, sub
chronic, and latent impacts of dilbit exposure in early life stage sockeye,
information that is critical for a proper risk analysis of the impact of a dilbit
spill on this socioeconomically important fish species.
PMID- 29966911
TI - Comprehensive Study of Cultivation Conditions and Methods on Lipid Accumulation
of a Marine Protist, Thraustochytrium striatum.
AB - This research studied the influences of cultivation conditions (carbon/nitrogen
source concentration, initial pH, salinity, and rotation speed) on cell growth
and fatty acid (FA) production/composition of a marine protist, Thraustochytrium
striatum. Fed-batch was also studied to improve cell growth and FA production.
The optimum cell growth (~5g/L dry cell mass, DCM) occurred under the cultivation
conditions of T=25 degrees C, glucose=30g/L, yeast extract/peptone (YEP)=4g/L,
salinity=100% of seawater, pH=6-7, and rotation speed=120rpm. Starch/glycerol and
yeast extract were the best carbon and nitrogen sources, respectively for
achieving the maximum cell growth. Low carbon/nitrogen (C/N) ratio benefited cell
growth while high C/N ratio was conducive to FA accumulation. The maximum lipid
content of 25% (g/g DCM) was obtained at glucose/YEP of 30/1 (w/w). Starch and
ammonia chloride were suggested to be used as carbon and nitrogen sources.
Compared to batch, fed-batch increased FA content significantly from 27 to 38%,
primarily including 35% of C16:0, 42% of C18:1, 9% of C18:2 and 5% of EPA/DHA.
The major FAs of T. striatum were palmitic, stearic, oleic, and linoleic acids
along with a small amount of docosahexaenoic and eicosapentaenoic acids, which
suggests lipid from T. striatum be suitable for biodiesel production.
PMID- 29966912
TI - Incomplete Reproductive Isolation Between Genetically Distinct Sympatric Clades
of the Pennate Model Diatom Seminavis robusta.
AB - Incomplete reproductive isolation between genetically distinct taxa provides an
interesting opportunity for speciation and adaptation studies. This phenomenon is
well-described in macro-organisms, but less experimental evidence is available
for unicellular eukaryotes. Here, we document the sympatric occurrence of
genetically differentiated populations of the pennate model diatom Seminavis
robusta in coastal subtidal biofilm communities and show widespread potential for
gene flow between them. Based on sequence variation in the plastid-encoded rbcL
gene, three distinct clades were identified. Morphological variation between the
clades reflected their phylogenetic relationships, with subtle differences in
valve morphology in the most distant clade compared to the other two clades,
which were indistinguishable. Using a large number of experimental crosses we
showed that, although reproductive output was significantly lower compared to the
majority of within-clade crosses, approximately 34.5% of the inter-clade crosses
resulted in viable and fertile progeny. While the nature of the incomplete
reproductive isolation remains unknown, its occurrence in natural diatom
populations represents an additional mechanism contributing to population genetic
structuring and adaptation and can spur further research into the mechanisms of
species divergence and the maintenance of species identity in the presence of
gene flow.
PMID- 29966913
TI - A new approach to differentiate states of mind wandering: Effects of working
memory capacity.
AB - Although widely studied, the process of how mind wandering occurs and is
subsequently sustained still remains unclear. Moreover, the traditional concept
of mind wandering tendency/frequency based on the self- or probe-caught methods
alone is incoherent and problematic. We developed a new approach to characterize
the mind wandering process by combining the self-caught and probe-caught methods
to estimate the time of focus and time of mind wandering separately, and examined
their relationship to working memory capacity. Participants performed an OSPAN
task and subsequently a basic Mindfulness Meditation Task (focus on breath).
During the meditation task, participants indicated when they became aware that
they were mind wandering (self-caught method), or were asked if they were mind
wandering when probed (probe-caught method). Results showed that time of focus
but not time of mind wandering increased with greater working memory capacity.
This suggests that individuals with higher working memory capacity were able to
focus on the current task longer, but had little effect on the ability to monitor
and terminate mind wandering once it occurred. The theoretical and methodological
implications of this new approach are discussed.
PMID- 29966914
TI - Vision dominates in perceptual language: English sensory vocabulary is optimized
for usage.
AB - Researchers have suggested that the vocabularies of languages are oriented
towards the communicative needs of language users. Here, we provide evidence
demonstrating that the higher frequency of visual words in a large variety of
English corpora is reflected in greater lexical differentiation-a greater number
of unique words-for the visual domain in the English lexicon. In comparison,
sensory modalities that are less frequently talked about, particularly taste and
smell, show less lexical differentiation. In addition, we show that even though
sensory language can be expected to change across historical time and between
contexts of use (e.g., spoken language versus fiction), the pattern of visual
dominance is a stable property of the English language. Thus, we show that across
the board, precisely those semantic domains that are more frequently talked about
are also more lexically differentiated, for perceptual experiences. This
correlation between type and token frequencies suggests that the sensory lexicon
of English is geared towards communicative efficiency.
PMID- 29966915
TI - Therapeutic potential of quercetin as a cardiovascular agent.
AB - Flavonoids are integral components of various vegetation and in foods;
consequently, they represent an inevitable part of the diet. Historical and
epidemiological proof recommend that diet plans consisting of flavonoids such as
quercetin have positive health benefits, especially on the heart. Flavonoids have
been proven to be active against hypertension, inflammation, diabetes and
vascular diseases. Quercetin exhibits significant heart related benefits as
inhibition of LDL oxidation, endothelium-independent vasodilator effects,
reduction of adhesion molecules and other inflammatory markers, the protective
effect on nitric oxide and endothelial function under conditions of oxidative
stress, prevention of neuronal oxidative and inflammatory damage and platelet
antiaggregant effects. Searching for experimental evidence to validate the
cardioprotective effects of quercetin, we review here the recent detailed in vivo
studies. Quercetin and its derivatives lead to an enhancement in heart features,
indicating the prospective for quercetin to be used therapeutically in the
treatment of cardiac diseases. Several evidence-based studies suggest mechanisms
to observe cardiovascular diseases such as aging effects, hypertension,
angiotensin-converting enzyme activity and endothelial-dependent and independent
functions. Different animal models including human are also used to elucidate the
in vivo role of quercetin in cardiovascular diseases. The role of quercetin and
its derivatives may go beyond their existence in food and has potential as a lead
molecule in drug development programs.
PMID- 29966916
TI - Design, synthesis, in vitro and in silico evaluation of a new series of
oxadiazole-based anticancer agents as potential Akt and FAK inhibitors.
AB - In the current work, new 1,3,4-oxadiazole derivatives were synthesized and
investigated for their cytotoxic effects on A549 human lung adenocarcinoma, C6
rat glioma and NIH/3T3 mouse embryonic fibroblast cell lines. Compounds 2, 6 and
9 were found to be the most potent anticancer agents against A549 and C6 cell
lines and therefore their effects on apoptosis, caspase-3 activation, Akt, FAK,
mitochondrial membrane potential and ultrastructural morphological changes were
evaluated. N-(5-Nitrothiazol-2-yl)-2-[[5-[((5,6,7,8-tetrahydronaphthalen-2
yl)oxy)methyl]-1,3,4-oxadiazol-2-yl]thio]acetamide (9) increased early and late
apoptotic cell population in A549 and C6 cells more than cisplatin and caused
more mitochondrial membrane depolarization in both cell lines than cisplatin. On
the other hand, N-(6-methoxybenzothiazol-2-yl)-2-[[5-[((5,6,7,8
tetrahydronaphthalen-2-yl)oxy)methyl]-1,3,4-oxadiazol-2-yl]thio]acetamide (6)
caused higher caspase-3 activation than cisplatin in both cell lines. Compound 6
showed significant Akt inhibitory activity in both cell lines. Moreover, compound
6 significantly inhibited FAK (Phospho-Tyr397) activity in C6 cell line.
Molecular docking simulations demonstrated that compound 6 fitted into the active
sites of Akt and FAK with high affinity and substrate-specific interactions.
Furthermore, compounds 2, 6 and 9 caused apoptotic morphological changes in both
cell lines obtained from micrographs by transmission electron microscopy. A
computational study for the prediction of ADME properties of all compounds was
also performed. These compounds did not violate Lipinski's rule, making them
potential orally bioavailable anticancer agents.
PMID- 29966917
TI - Synthesis and antibacterial bioactivities of cationic deacetyl linezolid
amphiphiles.
AB - Bacterial infections cause various life-threatening diseases and have become a
serious public health problem due to the emergence of drug-resistant strains.
Thus, novel antibiotics with excellent antibacterial activity and low
cytotoxicity are urgently needed. Here, three series of novel cationic deacetyl
linezolid amphiphiles bearing one lipophilic alkyl chain and one non-peptidic
amide bond were synthesized and tested for antimicrobial activities. Several
compounds showed excellent antibacterial activity toward drug-sensitive bacteria
such as gram-negative bacteria Escherichia coli (E. coli), Salmonella enterica
(S. enterica) and gram-positive Staphylococcus aureus (S. aureus), Enterococcus
faecalis (E. faecalis). Moreover, these amphiphilic molecules also exhibited
strong activity against drug-resistant species such as methicillin-resistant S.
aureus (MRSA), KPC (Klebsiella pneumoniae carbapenemase) and NDM-1 (New Delhi
metallo-beta-lactamase 1) producing carbapenem-resistant Enterobacteriaceae
(CRE). For example, the MICs (minimum inhibitory concentrations) of the best
compound 6e, ranged from 2 to 16 MUg/mL and linezolid ranged from 2 to >64 MUg/mL
against these strains. Therefore, 6e is a broad-spectrum antimicrobial compound
that may be a suitable lead as an antibiotic. The molecule 6e were found to
function primarily by permeabilization and depolarization of bacterial membranes.
Importantly, bacterial resistance against compound 6e was difficult to induce,
and 6e was stable under plasma conditions and showed suitable activity in
mammalian plasma. Thus, these compounds can be further developed into a potential
new class of broad-spectrum antibiotics.
PMID- 29966918
TI - Tracing simultaneous cadmium accumulation from different uptake routes in brown
crab Cancer pagurus by the use of stable isotopes.
AB - High concentrations of cadmium in brown crab are an issue of food safety, and
large variations between different areas have been found. To investigate the
relative importance of dietary and aqueous uptake regarding the overall
accumulation in brown crab, we used stable isotopes to trace the uptake from both
routes simultaneously in the same animals. We demonstrated that the analytical
challenges regarding background concentrations of natural isotope distribution
and polyatomic interferences in the different matrices can be overcome with an
appropriate analytical setup and modern mathematical corrections using a computer
software. Cadmium was accumulated via both routes and was found in all measured
organs at the end of the exposure phase. The obtained data were used to establish
accumulation curves for both uptake routes and estimate accumulation parameters
for hepatopancreas, as the most important organ in crab regarding total cadmium
body burden. Using the estimated parameters in combination with naturally
relevant cadmium concentrations in seawater and diet in a model, allowed us to
predict the relative importance of the aqueous and dietary uptake route to the
total hepatopancreas burden. According to the prediction, the dietary route is
the main route of uptake in brown crab with a minimum of 98% of the accumulated
cadmium in hepatopancreas originating from diet. Future studies addressing the
source and accumulation of cadmium in crab should therefore focus on the uptake
from feed and factors connected to foraging.
PMID- 29966919
TI - Assessing the effectiveness of New York's 911 Good Samaritan Law-Evidence from a
natural experiment.
AB - BACKGROUND: Drug overdose is the leading cause of accidental death in the United
States. Nationally, opioids are the primary drugs associated with accidental
overdoses. In response to increasing overdose deaths, 40 states and the District
of Columbia have enacted Good Samaritan Laws (GSLs). Generally, these policies
attempt to encourage witnesses or those experiencing an overdose to call 911 by
providing limited immunity from arrest, charge and/or prosecution of possession
of narcotics. The aim of the current study is to evaluate the effectiveness of
New York State's 911 GSL. METHODS: We exploit a difference in state law between
New York State, where the policy was adopted in 2011, and New Jersey, where the
policy was not adopted until 2013, to provide a reasonable comparison condition.
We examine variation in accidental opioid overdose emergency department visits
and inpatient admissions from 2010 to 2012 across 270 hospitals in New York and
New Jersey at the quarterly level controlling for hospital fixed effects and time
trends using State Emergency Department Databases (SEDD) and State Inpatient
Databases (SID). RESULTS: Accidental opioid overdose emergency department visits
and inpatient hospital admissions were increasing in both New York and New
Jersey. After the enactment of New York's 911 GSL, emergency department visits
and inpatient hospital admissions for accidental heroin overdoses increased
differently in New York and New Jersey, with an incident rate ratio (IRR) of 1.34
(95% CI = 1.00, 1.86). The results were inconclusive for accidental non-heroin
opioid overdoses (IRR = 0.98, 95% CI = 0.86, 1.13). CONCLUSIONS: Accidental
heroin overdose emergency department visits and inpatient hospital admissions
increased in New York State after the enactment of the 911 GSL, consistent with
the intended effect of the GSL. Preliminary evidence suggests that either persons
who use heroin and/or those around them were impacted by the policy change.
PMID- 29966920
TI - A DNA nanostructured aptasensor for the sensitive electrochemical detection of
HepG2 cells based on multibranched hybridization chain reaction amplification
strategy.
AB - Sensitive detection of cancer cells is beneficial to the early diagnosis of
cancer and individual treatment. In the present study, a DNA nanostructured
aptasensor was used for the sensitive electrochemical detection of human liver
hepatocellular carcinoma cells (HepG2) based on multibranched hybridization chain
reaction amplification strategy. We established a well-designed platform by
immobilizing DNA tetrahedron, a three-dimensional DNA nanostructure, on the gold
electrode to capture HepG2 cells more specifically and efficiently. Meanwhile,
functional hybrid nanoprobes consisted of MIL-101@AuNPs (Au nanoparticles),
numerous hemin/G-quadruplex DNAzyme from multibranched hybridization chain
reaction, and natural horseradish peroxidase (HRP) was designed. The hybrid
nanoprobes possessed the functions of specific discernment and enzymatic signal
amplification simultaneously. With the help of nanoprobes, HepG2 cells were
recognized and captured to form a DNA tetrahedron-cell-nanoprobe sandwich-like
structure on the electrode surface. The lower detection limit of this established
cytosensor is 5 cells per ml. Moreover, it delivered a broad detection range from
102 to 107 cells per ml. The results revealed that the as-proposed cytosensor may
be utilized as a powerful tool for early diagnosis of cancer in the future.
PMID- 29966921
TI - In situ enzymatic generation of gold for ultrasensitive amperometric sandwich
immunoassay of procalcitonin.
AB - Procalcitonin (PCT) is an important indicator for bacterial inflammatory
diseases, and its sensitive, accurate and rapid detection has important clinical
value. On the basis of sandwich immunoassay, glucose oxidase-catalyzed gold
deposition and in-situ microliter-droplet anodic stripping voltammetry (ASV) of
the enzyme-generated gold directly on the immunoelectrode, the ultrasensitive
electrochemical detection of PCT is achieved. A new method of the chemical
dissolution of gold by an appropriately diluted aqua regia and the simultaneous
cathodic preconcentration of gold on the immunoelectrode is suggested, which
gives the better performance for the ASV analysis of gold than the reported one.
Under optimized conditions, the ASV peak current is linear with the common
logarithm of PCT concentration from 0.05 fg mL-1 to 500 ng mL-1, with a limit of
detection (LOD, S/N = 3) as low as 0.04 fg mL-1. Our method has also been used
for detection of PCT in serum samples with satisfactory results.
PMID- 29966922
TI - An ultrasensitive biosensor for superoxide anion based on hollow porous PtAg
nanospheres.
AB - The accurate detection of the superoxide anion (O2*-) has vital academic and
medical diagnostic significance due to its important dual roles in biological
functioning. In this work, hollow porous PtAg nanospheres (PtAg HPNSs) were
fabricated by a facile hydrothermal method followed by a dealloying procedure.
The as-made PtAg nanospheres possessed hollow interiors and porous shells
composed of interconnected ligaments and pores with the typical size around 4 nm.
Benefitting from the unique hollow nanoporous architecture and the specific
alloying effect, the PtAg HPNSs showed high electrocatalytic activity towards
superoxide anions. The constructed biosensor based on PtAg HPNSs presented a fast
and ultrasensitive response in a wide range of 0.8-1080 nM with much higher
sensitivity of 4.5 * 10-2 MUA cm-2 nM-1 and low detection limit of 0.2 nM (S/N =
3). Moreover, the novel biosensors can achieve electrochemical detection for O2*-
released from living cells, exhibiting outstanding real time detection capability
in cell environment. The facile controllable fabrication and unique sensing
performance for PtAg HPNSs offers potential practical applications in developing
highly sensitive and stable biosensor towards superoxide anion.
PMID- 29966923
TI - Flexible deep brain neural probe for localized stimulation and detection with
metal guide.
AB - In this paper, we present the design, fabrication, and performance evaluation of
a polyimide-based flexible neural probe for the precise site stimulation and
recording in the deep brain. The probe consists of five electrodes: one for
stimulation, another for ground and the other three for recording electrodes.
This probe is designed to be foldable, enabling easy insertion into the deep
brain via temporary tungsten guide sticks. Because of its small cross-sectional
area and the flexibility of the polyimide, the probe causes minimum damage to the
neural tissue and does not show any evidence of serious immune reactions such as
high density of macrophage or microglia. Around the simulation electrodes, an
additional ground electrode prevents the stimulation of the undesired sites in
the brain. To ensure we stimulate the target point specifically, for instance STh
in this study, we confirm through both finite element analyses and in vitro
tests. With the additional ground electrodes, we observe the leakage power
decreased by about 80%. To check the performance of the probe, we demonstrate
animal experiments using rats, and neural spike signals from STh in the 7-mm deep
brain are successfully recorded after implantation.
PMID- 29966924
TI - Motivated empathy: a social neuroscience perspective.
AB - Empathy supports adaptive social behaviors such as cooperation and helping. It is
also fragile, and commonly unravels in contexts such as intergroup conflict.
Insights from neuroscience support the idea that empathy is context sensitive,
but recent findings suggest that empathy (and its fragility) reflect individuals'
motives in a given context rather than context alone. Here we explore motivated
empathy from the perspective of social neuroscience, examining how motives shape
empathy-related brain activity. We also describe recent motive-based empathy
interventions, their biological underpinnings, and their behavioral consequences.
Finally, we propose novel applications of recent neuroimaging techniques to
promote empathy, emotional wellbeing, and social adjustment.
PMID- 29966925
TI - Ensiling as pretreatment of rice straw: The effect of hemicellulase and
Lactobacillus plantarum on hemicellulose degradation and cellulose conversion.
AB - The fermentation characteristics, structural carbohydrate degradation and
enzymatic hydrolysis of rice straw ensiled with hemicellulase and Lactobacillus
plantarum were examined. Fresh rice straw was ensiled in 1-L laboratory silos
with no additive control (CK), L. plantarum (L), hemicellulase (HC) and
hemicellulase + L. plantarum (HCL) for 6, 15, 30 and 60 days. All additives
increased lactic acid concentration, and reduced pH and lignocellulosic content
of the resulting silage relative to the control. The highest organic acid and
residual sugar contents and lignocellulose degradation were observed in HCL
silage. Hemicellulase alone or combined with L. plantarum improved the enzymatic
hydrolysis with higher glucose yield and cellulose convertibility. Fresh rice
straw ensiled with the combined additives increased feedstock preservation and
cellulose conversion, and is thus recommended as a biological pretreatment for
subsequent biofuel production.
PMID- 29966926
TI - Effects of molybdenum, selenium and manganese supplementation on the performance
of anaerobic digestion and the characteristics of bacterial community in
acidogenic stage.
AB - The addition of trace elements to aid anaerobic digestion has already been widely
studied. However, the effects of rare trace elements on anaerobic digestion
remain unclear. In this study, the effects of Mo, Se and Mn on anaerobic
digestion of rice straw were explored. The results showed the methane yield
increased by 59.3%, 47.1% and 48.9% in the first 10 days following addition of Mo
(0.01 mg/L), Se (0.1 mg/L) and Mn (1.0 mg/L), respectively. Toxic effects and the
accumulation of volatile fatty acids (VFAs) were observed when the Se, Mo and Mn
concentrations were greater than 100, 1000 and 1000 mg/L, respectively. The half
maximal inhibitory concentrations (IC50) for Se, Mn and Mo were 79.9 mg/L, 773.9
mg/L and 792.3 mg/L, respectively. The addition of trace elements has changed the
bacterial structure of the bacteria, which in turn has affected the digestion
performance.
PMID- 29966927
TI - Bioreduction of azo dyes was enhanced by in-situ biogenic palladium
nanoparticles.
AB - Biogenic nanoparticles are promising materials for their green synthesis method
and good performance in stimulation on reduction of environmental contaminants.
In this study, Pd(0) nanoparticles (bio-Pd) were generated by Klebsiella oxytoca
GS-4-08 in fermentative condition and in-situ improved the azo dye reduction. The
bio-Pd was mainly located on cell membrane with a size range of 5-20 nm by TEM
and XRD data analyses. Anthraquinone-2-disulfonate (AQS) greatly increased the
reduction rate of Pd(II) with a reduction efficiency as high as 96.54 +/- 0.23%
in 24 h. The quinone respiration theory, glucose metabolism and the biohydrogen
pathway were used to explain the enhancement mechanism of the in-situ generated
bio-Pd on azo dye reduction. These results indicate that the in-situ generated
bio-Pd by K. oxytoca strain is efficient for azo dye reduction without complex
preparation processes, which is of great significance for the removal and
subsequent safe disposal of hazardous environmental compounds.
PMID- 29966928
TI - Effects of bioleaching pretreatment on nitrous oxide emission related functional
genes in sludge composting process.
AB - The effect of bioleaching pretreatment on N2O generation in sludge composting
process was firstly investigated in this study. The relationships among
physicochemical factors, N2O and NH3 emission and related functional genes were
analyzed in 60 days composting of bioleaching dewatering sludge (BDS) and filter
press dewatering sludge (FDS), respectively. The results showed the cumulative
amounts of NH3 and N2O emission from the BDS composting system were reduced by
83.52% and 54.76% after bioleaching pretreatment, respectively. The lower
moisture and pH, and the higher ORP and the concentrations of NH4+-N, NO3--N and
NO2--N were observed in BDS during the composting compared to FDS. Furthermore,
bioleaching pretreatment improved the relative abundance of hao but reduced amoA,
nirK and norB in the BDS during the composting. The low pH level and the
reduction of nirK and norB in BDS were the main reasons mitigating NH3 and N2O
emissions, respectively.
PMID- 29966929
TI - Novel kinetic studies on biomass hydrothermal carbonization.
AB - This work aims to study kinetic data on biomass hydrothermal carbonization by a
new point of view. The time course of essential properties signaling hydrochar
evolution is found to be sigmoidal ubiquitously. The logistic curve here
proposed, attributable to the Hill equation, furnished near-perfect regressions
(R2 as high as 0.999) in all cases studied. The broad applicability and the
excellent correlations stimulated the research heuristically and routed process
optimization. The evidence is reported that the success of fittings bases on
profound mechanistic reasons. Arguments are discussed supporting the hypothesis
that hydrochar formation is a stochastic phenomenon. The method deduces the Hill
equation by applying statistical methods to the hydrothermal carbonization,
modeled as a discrete Markov-chain process. The role of the model equation
parameters is also discussed. The potentiality of the method proposed in this
pioneering work could pave the way for a new paradigm in the modeling of
hydrothermal carbonization.
PMID- 29966930
TI - Immediate and long-term effects of bilateral electroconvulsive therapy on
cognitive functioning in patients with a depressive disorder.
AB - BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for
patients suffering from major depression. However, its use is limited due to
concerns about negative effects on cognition. Unilateral ECT is associated with
transient cognitive side-effects, while case-controlled studies investigating the
effect of bilateral ECT on cognition remain scarce. We investigate the effects of
bilateral ECT on cognition in depression in a longitudinal case-controlled study.
We hypothesize that adverse cognitive effects of bilateral ECT are transient
rather than long-term. METHODS: A total of 48 depressed patients and 19 controls
were included in the study and assessed with a battery of cognitive tests,
including tests of: working memory, verbal fluency, visuospatial abilities,
verbal/visual memory and learning, processing speed, inhibition, attention and
task-switching, and premorbid IQ. Patients underwent three cognitive assessments:
at baseline (n = 43), after ten ECT sessions (post-treatment; n = 39) and six
months after the tenth ECT session (follow-up; n = 25). Healthy controls
underwent the same cognitive assessment at baseline and after five-weeks.
RESULTS: Within the patient group, transient adverse cognitive side-effects were
observed for verbal memory and learning, and verbal fluency. None of the
cognitive domains tested in this study showed persisting impairments.
LIMITATIONS: A relatively high attrition rate is observed and autobiographical
memory was not assessed. CONCLUSION: This study shows that bilateral ECT has
negative cognitive effects on short-term. These effects could be explained by a
decrease in cognitive performance, a lack of learning effects or a combination.
However, the decrease in cognitive functioning appears to recover after six
months.
PMID- 29966931
TI - Prevalence and predictors of physician recommendations for medication adjustment
in bipolar disorder treatment.
AB - BACKGROUND: Successful medication management for bipolar disorder requires
clinicians to monitor and adjust regimens as needed, to achieve maximum
effectiveness and patient adherence. This study aims to measure the prevalence of
indications for medication adjustment at visits for bipolar disorder treatment;
the frequency with which physicians recommend medication adjustments; and how
strongly the indications predict the adjustments. METHODS: Data included 3,094
visits for 457 patients in Bipolar CHOICE, a comparative effectiveness study that
compared treatment with lithium versus quetiapine. A set of indications for
adjustment was matched to reports of whether the physician recommended a
medication adjustment at that visit, and what type. Associations between
indication and adjustment were examined using bivariate tests and hierarchical
logistic mixed effects models. RESULTS: Medication adjustment was recommended at
63% of the visits where one of the indications was present, and at 53% of all
visits. In multivariable analyses, adjustment was more likely to be recommended
if there was an indication of non-response or side effects, for patients who
started on quetiapine rather than lithium, or for patients who were female,
married, employed or more educated. LIMITATIONS: The study's cross-sectional
design implies that observed associations could result from confounding
variables. Also, the CHOICE trial placed certain restrictions on physicians'
medication choices, although this is not likely to have resulted in major
alterations of prescribing patterns. CONCLUSIONS: Clinical inertia may help
explain the lack of any adjustment recommendation at 37% of the visits where one
of the indications was present. Other explanations could also apply, such as
watchful waiting.
PMID- 29966932
TI - Mortality in treatment-resistant unipolar depression: A register-based cohort
study in Sweden.
AB - BACKGROUND: The impact of treatment resistant depression (TRD) on mortality is
not established. METHODS: Using Swedish national registers, 118,774 patients
between 18-69 years of age who had been prescribed an antidepressant and been
diagnosed with depression in specialized care were identified. Patients with at
least two additional treatment trials during the same depressive episode were
classified as having TRD. Data on the covariates of sex, age, history of
depression, self-harm, substance use disorders, and other psychiatric and somatic
comorbidities was also used. Relative risks comparing TRD patients with other
depressed patients were calculated as hazard ratios (HR) for all-cause mortality
and for external and non-external causes of death, as well as excess mortality
rate ratios (EMRR), with 95% confidence intervals (CI). RESULTS: In total 15,013
patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was
1.35 (95% CI 1.21-1.50). Mortality from external causes (including suicides and
accidents) was markedly higher in TRD patients than in other depressed patients
(HR 1.97; 1.69-2.29), while mortality from non-external causes was similar. The
adjusted EMRR was 1.52 (1.31-1.76), highest among patients 18-29 years old (EMRR
2.03; 1.31-1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63-2.43).
LIMITATIONS: Severity of depression and adherence to treatment were not available
in the data. CONCLUSIONS: Patients with TRD may have an increased all-cause
mortality compared to other depressed patients, mainly for external causes of
death. The relative mortality is highest among young and physically healthy
patients.
PMID- 29966933
TI - Does the preoperative lumbar sagittal profile affect the selection of osteotomy
level in pedicle subtraction osteotomy for thoracolumbar kyphosis secondary to
ankylosing spondylitis?
AB - OBJECTIVE: To investigate the different preoperative lumbar sagittal profiles of
ankylosing spondylitis (AS) patients and the selection of osteotomy level for one
level pedicle subtraction osteotomy (PSO) for the correction of thoracolumbar
kyphosis. PATIENTS AND METHODS: Seventy-one consecutive AS patients with an
average age of 35.3 years and a mean follow-up time of 35.9 months who underwent
one-level PSO for thoracolumbar kyphosis were divided into 2 groups based on
their preoperative lumbar sagittal profiles as follows: group A, lordotic lumbar
sagittal profiles; and group B, kyphotic lumbar sagittal profiles. The following
radiological parameters were measured and compared: chin-brow vertical angle
(CBVA), global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL),
sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT) and sacral
slope (SS). Clinical evaluation included Oswestry Disability Index (ODI) and
Visual Analogue Scale (VAS). Perioperative and mid-term complications were
reviewed. RESULTS: There were 28 patients in group A and 43 in group B. The
preoperative LL was -21.0 degrees in group A and 2.3 degrees in group B (P <
0.05). The preoperative SVA was 122.5 mm in group A and 184.3 mm in group B (P <
0.05). All the patients in group A (100%) underwent PSO at L1/L2, while 90% of
group B patients underwent PSO at L2/L3, with no significant difference of
postoperative GK, LL and SVA between the 2 groups (P > 0.05). No obvious loss of
correction was observed in either group at the final follow-up. The correction of
LL and SVA showed a strong but not statistically significant increasing trend as
the PSO level descended from L1 to L3 (P > 0.05). The postoperative ODI was
significantly lower in patients underwent PSO at L1 or L2 (P < 0.05).
CONCLUSIONS: Patients in group B had significantly worse preoperative sagittal
alignments compared to group A. The distribution of osteotomy levels varied
between the 2 groups due to the different lumbar profiles; however, satisfactory
correction was achieved in both groups. The preoperative lumbar profiles need to
be considered in selecting the optimal osteotomy level. Patients with kyphotic
lumbar profiles are suitable candidates for PSO at L2/L3, while L1/L2 PSO is
appropriate for patients with lordotic lumbar profiles.
PMID- 29966934
TI - 24-Epibrassinolide; an active brassinolide and its role in salt stress tolerance
in plants: A review.
AB - Salt stress is one of most dramatic abiotic stresses, reduces crop yield
significantly. Application of hormones proved effective salt stress ameliorating
approach. 24-Epibrassinolide (EBL), an active by-product from brassinolide
biosynthesis shows significant salt stress tolerance in plants. EBL application
improves plant growth and development under salt stress by playing as signalling
compound in different metabolic and physiological processes. This article
compiles all identified ways by which EBL improves plant growth and enhances crop
yield. Furthermore, EBL enhances photosynthetic rate, reduces ROS production and
plays important role in ionic homeostasis. Furthermore EBL-induced salt stress
tolerance suggest that complex transcriptional and translational reprogramming
occurs in response to EBL and salt stress therefore transcriptional and
translational changes in response to EBL application are also discussed in this
article.
PMID- 29966935
TI - Interrogation of the Gulf toadfish intestinal proteome response to hypersalinity
exposure provides insights into osmoregulatory mechanisms and regulation of
carbonate mineral precipitation.
AB - Marine bony fish live in a hyperosmotic environment and maintain osmotic
homeostasis by drinking seawater, and absorbing salt and water across their
gastrointestinal tract. Although the ion and water transport mechanisms in the
intestine have been the subject of much study, numerous questions remain
unanswered. To address some of these questions, a shotgun proteomics methodology
employing isobaric tandem mass tags (TMT) was used to interrogate the anterior
intestine, posterior intestine, and intestinal fluid proteomes of Gulf toadfish
(Opsanus beta) acclimated to normal (35 ppt) or hypersaline (60 ppt) seawater.
Relative protein abundance between tissues was also investigated using label free
quantitation. Protein products from nearly 3000 unique toadfish loci were
identified and quantified between the tissues, and pathway analysis was performed
to gain insight into biological significance. Numerous proteins potentially
involved in ion transport, digestion, nutrient absorption, and intestinal CaCO3
precipitation were found to respond to changing salinity, providing additional
insight into the molecular mechanisms behind these processes. Intestinal protein
heterogeneity was also observed with proteins involved in ion transport
responding to hypersalinity exposure primarily in the anterior intestine, and
proteins involved in digestion and nutrient absorption showing higher abundance
in the anterior intestine, regardless of salinity.
PMID- 29966936
TI - Checkpoint inhibitors as treatment for malignant gliomas: "A long way to the
top".
AB - Glioblastoma is the most common and lethal malignant brain tumor in adults, with
a very poor prognosis of less than two years despite surgical resection followed
by radiotherapy and chemotherapy. To date, targeted agents and antiangiogenic
therapy have failed to show survival benefits and novel treatment approaches are
urgently needed. Immune checkpoint inhibitors have recently revolutionized the
landscape of cancer immunotherapy achieving regulatory approvals for a number of
other 'historically' resistant cancers. These exciting successes have generated
great interest in investigating if these agents could be such effective also in
brain tumors field. Moreover, the traditional dogma that considers the central
nervous system (CNS) as an immune-privileged site lacking the potential for
immunosurveillance has been challenged as it has become clear that the CNS is
immunoactive. Critical barriers to an effective antitumor immunity in brain tumor
patients are still represented by the peculiar CNS immunological milieu and the
numerous systemic and local immunosuppressive forces exhibited by malignant
gliomas to avoid immune recognition and cellular death. This review describes the
current status of checkpoint modulation as treatment for malignant gliomas. We
start illustrating the compelling molecular and immunological rationale, than we
show striking preclinical evidence of activity and discuss available data from
prospective clinical trials. Furthermore, we explore the role of predictive
biomarkers of responsiveness to checkpoint blockade in the context of gliomas,
along with the development of combinatorial and potentially synergistic
approaches with other established anti-cancer treatments or complementary
immunotherapeutic modalities.
PMID- 29966937
TI - 1,5-Anhydro-d-glucitol in vitreous humor and cerebrospinal fluid - A helpful tool
for identification of diabetes and diabetic coma post mortem.
AB - Since there are no characteristic morphological findings post mortem diagnosis of
diabetes mellitus and identification of diabetic coma need to be confirmed by
suitable biomarkers. The postmortem identification of preexisting hyperglycemia
or diabetic coma can be difficult if the matrices for the determination of the
established biomarkers are not available or the obtained results are close to the
established cut-off values. 1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of
glucose, competes with glucose for renal reabsorption. Therefore low serum
concentrations of 1,5-AG, reflect hyperglycemic excursions over the prior 1-2
weeks in diabetic patients. To evaluate postmortem 1,5-AG concentrations in
vitreous humor (VH) and cerebrospinal fluid (CSF), a liquid chromatographic mass
spectrometric method for the quantification of 1,5-AG in VH and CSF was developed
and validated according to international guidelines. In order to establish a cut
off for the identification of an ante mortem existing diabetes and the diagnosis
of a diabetic coma in deceased the relationships between 1,5-AG concentrations in
VH and CSF to other diabetes associated biochemical parameters of 47 non
diabetic, 86 diabetic and 9 cases of diabetic coma were examined. In 83 of these
cases, both matrices could be obtained and analyzed. Comparisons of the
respective HbA1c, Glucose in VH or Sum-formula of Traub to 1,5-AG concentrations
in VH and CSF resulted in correlation coefficients R2<=0.2. For the application
of 1,5-AG concentrations in VH against CSF, a linear regression gave a
correlation coefficient of R2=0.955. Comparable linear correlations of 1,5-AG
concentrations could be observed between VH and femoral venous blood (FVB)
(R2=0.839) as well as between CSF and FVB (R2=0.756). Due to overlapping
concentration ranges, the determination of a reliable cut-off for the
differentiation of diabetic disease to diabetic coma cases was not possible.
However, the 1,5-AG concentrations in VH and CSF in cases of deceased diabetics
were significantly lower (p<0.05) than in non-diabetic deceased and therefore
indicate a pre-existing diabetes or even a diabetic coma as the cause of death.
PMID- 29966938
TI - Evaluation of different methods for measuring 89Sr and 90Sr: Measurement
uncertainty for the different methods as a function of the activity ratio.
AB - In case of a radiological emergency situation involving e.g. fission of uranium
or plutonium, analysis of radioactive strontium will be of importance. The
primary radionuclides of interest are 90Sr, its progeny 90Y and 89Sr. A few days
following an event, 89Sr will be the predominant radioisotope of strontium. Most
methods found in the literature are valid and applicable when measuring 90Sr, but
when samples contain both 89Sr/90Sr interference problematics arise. How these
interferences are dealt with will have an effect on the uncertainty of the 90Sr
determination. This work aims at evaluating three measurement approaches, all
mentioned in the literature, with respect to the measurement uncertainty when
determining 90Sr in an emergency preparedness situation and to propose a suitable
measurement strategy.
PMID- 29966939
TI - Comparative study of the sensitivity of Daphnia galeata and Daphnia magna to
heavy metals.
AB - Daphnia galeata and Daphnia magna belong to the family Daphniidae. Daphnia
galeata has a smaller body size and longer helmet than D. magna. Although D.
galeata is widely distributed in the northern hemisphere, it is not as commonly
used in aquatic ecotoxicity tests as D. magna. There have been only few
ecotoxicological studies on the toxicity of heavy metals, organic matter, and
nanomaterials in D. galeata. Thus, there is a need to discover new test species
and expand the number of currently known test species to elucidate species
sensitivity to aquatic pollutants. We carried out a comparative study on the
sensitivity of D. magna (which represents the test water flea species) and D.
galeata to heavy metal toxicity. The acute toxicity values (EC50 and LC50) of 11
heavy metal species, including silver (Ag+), arsenite (As3+), cadmium (Cd2+),
chromate (Cr6+), cupric (Cu2+), ferrous (Fe2+), mercury (Hg2+), manganese (Mn2+),
nickel (Ni2+), lead (Pb2+), and zinc (Zn2+), in D. galeata and D. magna were
compared by conducting acute toxicity assays and comparing the data with the
available data. The age of the tested Daphnia individuals and the type of
exposure medium were considered for more reliable comparison of species
sensitivity. We observed that D. galeata was more sensitive to Ag+, As3+, Cr6+,
Fe2+, Ni2+, and Pb2+ than D. magna. The sensitivity to Cu2+, Cd2+, and Zn2+ was
similar for D. magna and D. galeata. This study presents important aquatic
toxicity and sensitivity data on D. galeata, which is not a widely used species
in aquatic ecotoxicology studies. Our results recommend D. galeata as a suitable
species for aquatic ecotoxicity tests because of its higher sensitivity.
PMID- 29966940
TI - Towards intelligent robust detection of anatomical structures in incomplete
volumetric data.
AB - Robust and fast detection of anatomical structures represents an important
component of medical image analysis technologies. Current solutions for anatomy
detection are based on machine learning, and are generally driven by suboptimal
and exhaustive search strategies. In particular, these techniques do not
effectively address cases of incomplete data, i.e., scans acquired with a partial
field-of-view. We address these challenges by following a new paradigm, which
reformulates the detection task to teaching an intelligent artificial agent how
to actively search for an anatomical structure. Using the principles of deep
reinforcement learning with multi-scale image analysis, artificial agents are
taught optimal navigation paths in the scale-space representation of an image,
while accounting for structures that are missing from the field-of-view. The
spatial coherence of the observed anatomical landmarks is ensured using elements
from statistical shape modeling and robust estimation theory. Experiments show
that our solution outperforms marginal space deep learning, a powerful deep
learning method, at detecting different anatomical structures without any
failure. The dataset contains 5043 3D-CT volumes from over 2000 patients,
totaling over 2,500,000 image slices. In particular, our solution achieves 0%
false-positive and 0% false-negative rates at detecting whether the landmarks are
captured in the field-of-view of the scan (excluding all border cases), with an
average detection accuracy of 2.78 mm. In terms of runtime, we reduce the
detection-time of the marginal space deep learning method by 20-30 times to under
40 ms, an unmatched performance for high resolution incomplete 3D-CT data.
PMID- 29966941
TI - Slice-level diffusion encoding for motion and distortion correction.
AB - Advances in microstructural modelling are leading to growing requirements on
diffusion MRI acquisitions, namely sensitivity to smaller structures and better
resolution of the geometric orientations. The resulting acquisitions contain
highly attenuated images that present particular challenges when there is motion
and geometric distortion. This study proposes to address these challenges by
breaking with the conventional one-volume-one-encoding paradigm employed in
conventional diffusion imaging using single-shot Echo Planar Imaging. By enabling
free choice of the diffusion encoding on the slice level, a higher temporal
sampling of slices with low b-value can be achieved. These allow more robust
motion correction, and in combination with a second reversed phase-encoded echo,
also dynamic distortion correction. These proposed advances are validated on
phantom and adult experiments and employed in a study of eight foetal subjects.
Equivalence in obtained diffusion quantities with the conventional method is
demonstrated as well as benefits in distortion and motion correction. The
resulting capability can be combined with any acquisition parameters including
multiband imaging and allows application to diffusion MRI studies in general.
PMID- 29966942
TI - Effects of diesel exhaust particles on the expression of tau and autophagy
proteins in human neuroblastoma cells.
AB - Particulate air pollution is recognized as a potential risk factor for
neurological disorders; however, the underlying mechanisms of neurodegenerative
diseases that occur due to particulate air pollution remain unclear. The
objective of the present study was to evaluate the neurotoxic effects caused by
diesel exhaust particles (DEPs). We determined the ability of DEPs and carbon
black (CB) to induce neurotoxicity, oxidative stress and inflammation, and to
disrupt the expression of tau and autophagy proteins in human neuroblastoma IMR
32 cells. Spherical CB (dominated by C, N, and S) and DEPs (dominated by C, N,
and O) in aggregates were observed using a field emission-scanning electron
microscope (FE-SEM) equipped with energy-dispersive x-ray (EDX) microanalysis.
Cell viability was significantly decreased by CB and DEPs in IMR-32 cells, but
neither particle altered malondialdehyde (MDA) production. We observed that
exposure to DEPs significantly increased 8-isoprostane and tumor necrosis factor
(TNF)-alpha levels. Significantly increased expression of tau was induced in IMR
32 cells by DEPs but not by CB. Expression of beclin 1 was increased by DEPs,
whereas the light chain 3II (LC3II)/LC3I ratio was increased by CB. Results of
the present study suggested that DEPs induced neuroinflammation, oxidative
stress, and neurodegenerative-related tau overexpression and regulation by
autophagy in IMR-32 cells. We demonstrated that DEPs are able to induce
neurotoxicity, which could be associated with the development of
neurodegenerative diseases.
PMID- 29966943
TI - Pogostone attenuates TNF-alpha-induced injury in A549 cells via inhibiting NF
kappaB and activating Nrf2 pathways.
AB - Pogostone (PO), a major component of Pogostemon cablin, displays potent
protective effects against lipopolysaccharide-induced acute lung injury (ALI) in
mice. This study aimed to investigate the protective effect of PO on TNF-alpha
induced cell injury in human alveolar epithelial cells in vitro and its
underlying mechanism. The cell viability was measured using the MTS method. The
cell apoptosis was determined using flow cytometry. The activities of reactive
oxygen species (ROS) were detected using a fluorescence microscope. The pro
inflammatory cytokines and antioxidant genes were assessed using reverse
transcription-polymerase chain reaction. The protein expression of Kelch-like ECH
associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2),
nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor
alpha (IkappaBalpha), and nuclear factor-kappa B (NF-kappaB) p65 was analyzed
using the Western blot analysis. PO alleviated cell apoptosis and inhibited ROS
production. It alleviated TNF-alpha-induced cell injury, suppressed the levels of
inflammatory cytokines [interleukin (IL)-6, IL-1beta, and IL-8], and enhanced the
expression of antioxidant genes (quinine oxidoreductase 1, glutamate cysteine
ligase catalytic subunit, heme oxygenase-1). It increased the expression of Keap1
and promoted the activation of Nrf2. However, the phosphorylation of IkappaBalpha
and the nuclear expression of NF-kappaB p65 decreased. The anti-inflammatory and
antioxidant effects of PO were abrogated following Nrf2 and NF-kappaB p65
knockdown. The results indicated a protective effect of PO against TNF-alpha
induced cell injury in A549 cells by modulating the balance between Nrf2 and NF
kappaB p65 signaling pathways. They verified PO as a promising anti-inflammatory
adjuvant drug for treating ALI.
PMID- 29966944
TI - Protective effect of pioglitazone on ovarian ischemia reperfusion injury of
female rats via modulation of peroxisome proliferator activated receptor gamma
and heme-oxygenase 1.
AB - Ovarian torsion is a dangerous gynecological emergency condition. Early diagnosis
of this case is necessary to preserve the function of the ovaries and fallopian
tubes and prevent further damage. Ovarian torsion means complete or partial
rotation of the adnexa with ischemia followed by reperfusion period. Ovarian
torsion affects 2%-15% of patients who have surgical treatment of adnexal masses.
We investigated the effect of pioglitazone (PIO) on induced ovarian ischemia
reperfusion (OIR). PIO (10, 30 mg/kg) was administered orally in the presence or
absence of induced OIR. We measured ovarian tissue malondialdehyde (MDA), total
nitrites (NOx), reduced glutathione (GSH), heme-oxygenase 1 (HO-1), and gene
expressions of peroxisome proliferator activated receptor gamma (PPARgamma),
tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS)
and endothelial nitric oxide synthase (eNOS). Moreover, expression of p53 and
histopathological changes were also evaluated. Results showed increase in the
ovarian tissue levels of MDA and NOx and gene expressions of p53, TNFalpha, and
iNOS in the induced OIR group. The induced OIR group showed the histopathological
changes associated with cell injury, marked ovarian edema, hemorrhage and
congestion. In addition, there was reduction in the GSH, HO-1 levels and
PPARgamma, eNOS gene expressions. PIO was able to reduce these induced OIR
changes to levels insignificant from control group. This protective effect of PIO
may be attributed to its PPARgamma agonist effect, anti-inflammatory, anti
apoptotic and anti-oxidant properties.
PMID- 29966945
TI - A Quality by Design (QbD) approach to the development of a gradient high
performance liquid chromatography for the simultaneous assay of curcuminoids and
doxorubicin from long-circulating liposomes.
AB - The present study highlights the advantages of using an Analytical Quality by
Design (AQbD) approach to the optimization of a high-performance liquid
chromatography method for the simultaneous assay of curcumin (CUR),
demetoxycurcumin (DMC), bisdemetoxycurcumin (BDMC) and doxorubicin (DOX) co
encapsulated in long circulating liposomes. Within the QbD paradigm, the present
study aimed to establish the method operable design region (MODR) for the
optimization of the high-performance liquid chromatography-fluorescence (HPLC
FLD) assay by means of Design of Experiments (DOE) and response surface
methodology, in order to achieve a good separation and quantification of all
analyzed compounds along to an acceptable analysis time. A deep understanding of
the quality target product profile (QTPP) and of the analytical target profile
(ATP), followed by a risk assessment for variables that affect the efficiency of
the method led to the development of a precise, accurate and cost-effective
method. The assay was linear over the range of 2-20 MUg/ml for all investigated
compounds. The intra-and inter-day precision were less than 2%, with accuracies
between 97-104% of the true values. The method was successfully applied to the
quantification of curcuminoids and DOX from long-circulating liposomes.
PMID- 29966946
TI - Interval importance index to select relevant ATR-FTIR wavenumber Intervals for
falsified drug classification.
AB - The commerce of falsified drugs has substantially grown in recent years due to
facilitated access to technologies needed for copying authentic pharmaceutical
products. Attenuated Total Reflectance coupled with Fourier Transform Infrared
(ATR-FTIR) spectroscopy has been successfully employed as an analytical tool to
identify falsified products and support legal agents in interrupting illegal
operations. ATR-FTIR spectroscopy typically yields datasets comprised of hundreds
of highly correlated wavenumbers, which may compromise the performance of
classical multivariate techniques used for sample classification. In this paper
we propose a new wavenumber interval selection method aimed at selecting regions
of spectra that best discriminate samples of seized drugs into two classes,
authentic or falsified. The discriminative power of spectra regions is
represented by an Interval Importance Index (III) based on the Two-Sample
Kolmogorov-Smirnov test statistic, which is a novel proposition of this paper.
The III guides an iterative forward approach for wavenumber selection; different
data mining techniques are used for sample classification. In 100 replications
using the best combination of classification technique and wavenumber intervals,
we obtained average 99.87% accurate classifications on a Cialis(r) dataset, while
retaining 12.5% of the authentic wavenumbers, and average 99.43% accurate
classifications on a Viagra(r) dataset, while retaining 23.75% of the authentic
wavenumbers. Our proposition was compared with alternative approaches for
individual and interval wavenumber selection available in the literature, always
leading to more consistent and easier to interpret results.
PMID- 29966947
TI - Synchronous triple squamous cell carcinoma of the esophagus.
AB - BACKGROUND: Synchronous multiple primary malignancies of the esophagus and other
organs are relatively unusual, but only five articles have published two
synchronous cancers, both in the esophagus. This is the first published case of a
triple esophageal carcinoma. CASE REPORT: A 43-year-old man was referred to our
hospital with severe progressive dysphagia and epigastric pain for almost one
year. Endoscopy and imaging exams revealed three tumors located in upper, middle
and lower esophagus. The upper and middle esophageal cancers were irresectable,
and the patient was treated with radio- and chemotherapy. He survived 11 months
after the diagnosis and died due to severe undernutrition and bilateral
pneumonia. CONCLUSION: In presence of squamous cell carcinoma of the esophagus,
propedeutics should be carefully performed in order to verify the occurrence of
other synchronous tumors in the esophagus and other organs, mainly head and neck
and bronchial regions.
PMID- 29966948
TI - Sigmoid gallstone ileus: A case report and literature review in Japan.
AB - INTRODUCTION: Gallstone as a cause of bowel obstruction is rare, and its
occurrence in the colon is very infrequent. Here, we report the case of sigmoid
gallstone ileus treated with one-stage operation. CASE PRESENTATION: A 65-year
old man visited our hospital because of abdominal pain and nausea. On the basis
of the results of computed tomography, the patient was diagnosed with sigmoid
gallstone ileus through cholecystocolonic fistula, and an emergency laparotomy
was performed. Enterolithotomy, cholecystectomy, and fistula closure were
performed in one-stage operation. Postoperatively, the patient developed biliary
leakage, which rapidly recovered with conservative therapy. DISCUSSION AND
CONCLUSION: The surgical treatment of gallstone ileus remains controversial. For
postoperative infection control, one-stage operation can be considered for
patients with gallstone ileus associated with cholecystocolonic fistula.
PMID- 29966949
TI - Laparoscopic herniorrhaphy of bilateral inguinal herniae and an incidental
Spigelian hernia with intra corporeal suturing of the Spigelian hernia neck: A
case report.
AB - INTRODUCTION: A Spigelian hernia is a rare type of abdominal wall hernia
occurring in an area of congenital or acquired defect. These hernias occur in an
area called the Spigelian zone and are interparietal making for a difficult
diagnosis on clinical exam. PRESENTATION OF CASE: A 74-year-old female presenting
with bilateral inguinal herniae and a left sided Spigelian hernia. The repair was
done laparoscopically with an intra-corporeal suture closing the Spigelian hernia
neck. Her recovery was uneventful. DISCUSSION: The aetiology of Spigelian herniae
remains nebulous. Due to their rarity and evasive nature on clinical exam,
ultrasound imaging has become the first line in diagnosis. Open herniorrhaphy is
still the most common technique, but laparoscopic repair is becoming more
commonplace in the surgical armamentarium. CONCLUSION: Spigelian herniae are rare
with non specific symptoms. We present the first case report of a laparoscopic
repair of bilateral inguinal herniae and a left sided Spigelian hernia with intra
corporeal suturing of the Spigelian hernia neck.
PMID- 29966950
TI - Bilateral pulmonary embolism after arthroscopic anterior cruciate ligament
reconstruction: A case report.
AB - INTRODUCTION: Venous thromboembolism is a serious complication in orthopedic
surgery. It is very common in major surgery, such as total hip arthroplasty.
However, few reports have described the incidence of pulmonary embolism and its
associated risk factors following less invasive surgery, such as arthroscopic
knee surgery. PRESENTATION OF CASE: We describe a rare presentation of a young
man with bilateral pulmonary embolism of the main pulmonary arteries following
arthroscopic anterior cruciate ligament reconstruction. DISCUSSION: The present
patient is different from other similar cases in that he was an active healthy
man without any risk factors for the development of thrombosis. Despite this, he
experienced a bilateral pulmonary embolism one week after knee arthroscopy.
CONCLUSION: Although anterior cruciate ligament reconstruction is a common and
safe procedure performed on a daily basis, unexpected complications may occur.
One of these is venous thromboembolism which may be fatal.
PMID- 29966951
TI - Extraskeletal chondroma walling the temporomandibular joint: Report of a rare
case and review of the literature.
AB - INTRODUCTION: Extraskeletal or soft-tissue chondroma is a rare benign
cartilaginous neoplasm which usually affects hands and feet. Scientific
literature only reports one previous case of this pathology in the preauricular
region. PRESENTATION OF THE CASE: This report describes a rare case of
extraskeletal chondroma surrounding the temporomandibular joint of a 55-year-old
female patient. DISCUSSION AND CONCLUSION: Diagnosis of extraskeletal chondroma
is challenging since tissue swelling, diagnostic imaging and even
histopathological features may be misleading for other joint or gland
pathologies.
PMID- 29966952
TI - The first case of osteoma of the mandibular notch located both medially and
laterally and treated with a transoral endoscopy assisted approach. A case
report.
AB - INTRODUCTION: Osteomas are slow-growing benign tumours composed of mature compact
or cancellous bone and are seen in facial bones but uncommonly in the mandible;
cases that arise in the notch region are rarely reported in the literature.
PRESENTATION OF CASE: This article presents a 37-year-old woman with no
preauricular swelling, no limitation of joint motion and pain only on the left
side. DISCUSSION: The patient was evaluated based on preoperative clinical
manifestations, orthopantomography and a computed tomography (CT) scan. The CT
scan showed bone density irregularity between the coronoid process and the left
mandibular condyle in the notch region arising both medially and laterally.
Surgery was performed based on these images and the patient's indications and
symptoms. CONCLUSION: Among the cases of osteoma in the literature, only six
originated in the mandibular notch, but this is the only that was both medially
and laterally located.
PMID- 29966953
TI - Rare case of sacrococcygeal tuberculosis mimicking as an anal fistula.
AB - INTRODUCTION: Spinal tuberculosis (TB) is the most common manifestation of extra
pulmonary TB. TB of the lumbosacral junction is rare and occurs in only 1 to 2%
of all cases of spinal TB. Moreover, isolated sacrococcygeal TB is extremely
rare. Herein, we report a rare case of sacrococcygeal TB, which was difficult to
distinguish from complex anal fistula. CASE PRESENTATION: A 93-year-old man
presented with sacral pain and peri-anal discharge. He had pulmonary TB at 25
years of age. Fistulography revealed an abnormal tract that connected to the pre
sacrococcygeal area, which was not connected to the rectum. Computed tomography
scan showed fluid collection in front of the sacrum, with a lytic destruction of
the lower sacrum and coccyx. Cold abscess aspiration cytology was negative for
acid-fast bacilli. However, real-time polymerase chain reaction was positive for
Mycobacterium tuberculosis. His symptoms resolved immediately after the
initiation of anti-TB chemotherapy. CONCLUSION: This case highlights the
importance of considering tuberculosis as a diagnosis if the unusual sites are
involved.
PMID- 29966954
TI - Massive intraperitoneal free air induced by pneumothorax and pneumomediastinum.
AB - INTRODUCTION: Pneumoperitoneum (PP), or air within the abdominal cavity, is
frequently a harbinger of serious abdominal pathology and often represents
visceral perforation. We herein report a case of combined massive intraperitoneal
free air, pneumothorax and pneumomediastinum but emergency laparotomy was
negative. PRESENTATION OF CASE: A sixty-seven-year-old man was found unconscious
on a road after being hit by a car. On arrival, he showed swelling of the head
and flail chest. Computed tomography (CT) demonstrated cerebral contusion,
multiple bilateral rib fractures, minute subcutaneous emphysema and a left
hemothorax. As his consciousness and respiratory function deteriorated, tracheal
intubation with mechanical ventilation with positive end-expiratory pressure was
executed on the second day. On the third day, the CT scan revealed the new
appearance of pneumomediastinum and massive free air in his intraperitoneal
space. Emergency laparotomy was negative. DISCUSSION: The 'air leak' phenomenon,
in which an alveolar air cell ruptures into the perivascular and peribronchial
interstitial tissues, is a well-recognized consequence of positive end-expiratory
pressure therapy. Accordingly, the deterioration of traumatic pneumothorax and/or
the occurrence of pneumomediastinum after mechanical ventilation was the most
likely cause of the PP in the present case. However, it remains possible that a
minute unrecognized diaphragmatic injury caused the massive PP in the present
case. CONCLUSION: We herein described a case of PP that occurred after mechanical
ventilation in a patient with multiple injuries, but which did not originate from
perforation of the gastrointestinal tract. It is most likely that the PP had an
intrathoracic cause.
PMID- 29966955
TI - Paget-Schroetter syndrome as a result of 1st rib stress fracture due to gym
activity presenting with Urschel's sign - A case report and review of literature.
AB - BACKGROUND: Paget-Schrotter Syndrome (PSS) also known as "effort thrombosis" is a
form of primary thrombosis in the subclavian vein at the costoclavicular junction
is usually seen in younger patients after repeated strenuous activity of the
shoulders and arms. When occurring in younger patients, PSS presents itself with
predisposing factors such as unilateral dull, aching pain in the shoulder or
axilla and swelling of the arm and hand. CASE PRESENTATION: We report a rare case
of unusual left axillo-subclavian vein thrombosis following narrowing of thoracic
outlet due to stress injury of rib fracture likely during gym activity in absence
of other clear risk factors and a negative hypercoagulable workup in a 27-year
old man who was admitted as left deltoid rupture 5 days after his usual gym.
Subsequently he was transferred under vascular surgery for thrombectomy.
CONCLUSION: In addition to the unusual location in the left upper extremity in
our case, the absence of common etiologic factors makes our case of Paget
Schroetter Syndrome a very unique one. This case report aims to discuss the
common causes of PSS in order to raise a high index of suspicion in certain
groups of patients. This will allow early identification and avoidance of
catastrophic outcomes such as pulmonary embolism and stroke.
PMID- 29966956
TI - Laparoscopic treatment of an infected urachalcyst and diverticulum in a young
adult: Presentation of a case and review of the literature.
AB - INTRODUCTION: A urachal remnant is a rare anomaly in adults, with a heterogeneous
presentation. We report a case of an infected urachal cyst associated with a
urachal diverticulum. PRESENTATION OF CASE: We report the case of a 16-year-old
male who presented to our hospital with lower abdominal pain without any other
signs of general infection. A physical examination revealed umbilical erythema
with associated tenderness. All laboratory tests were normal. An ultrasound scan
revealed an urachal cyst near the umbilicus and a second cyst near the bladder
dome. We decided on a staged treatment with antibiotic administration followed by
surgical excision of the urachus during laparoscopy. The patient was discharged
on day 10 without complications. Pathology revealed chronic inflammatory tissue
without signs of malignancy. DISCUSSION: Urachus is a fibrous remnant of the
allantois that progressively obliterates after birth, forming the median
umbilical ligament. Incomplete regression of the urachal lumen results in several
anomalies. These anomalies require treatment when discovered because of an
increased risk of infection and neoplastic differentiation. A urachal cyst is the
most common type of anomaly, and infection is the usual mode of presentation.
Surgical intervention with complete excision of the urachus is the treatment of
choice. A staged approach with antibiotic administration followed by surgery is
recommended if signs of infection are present. CONCLUSION: Urachal anomalies in
adulthood are rare, with a nonspecific presentation. However, identifying a
urachal anomaly is important because of the increased risk for infection and
neoplastic differentiation. The laparoscopic approach is safe and patients
recover rapidly.
PMID- 29966957
TI - Neuroendocrine carcinoma arising in a tailgut cyst.
AB - INTRODUCTION: A tailgut cyst, also called retrorectal cystic hamartoma, is a rare
congenital lesion that forms most commonly in the retrorectal space. It is
presumed to arise from remnants of early embryogenesis. PRESENTATION OF CASE: The
following report describes a unique case of a retrorectal cystic hamartoma in a
53 year-old French Canadian man with a history of low back pain. The tumour
underwent malignant transformation into a well-differentiated neuroendocrine
carcinoma three years after the beginning of symptoms. DISCUSSION: This condition
can be found at any age, but occurs especially among middle-aged women. Not only
is it frequently misdiagnosed, but also several complications associated to the
cyst have been reported such as infection and malignant transformation. This is
why complete surgical excision of the tailgut cyst is currently recommended.
PMID- 29966958
TI - Effects of supplemental heat therapy in multimodal treated chronic low back pain
patients on strength and flexibility.
AB - BACKGROUND: The beneficial effects of thermotherapy on analgesia and relaxation
are widely known for various diseases. To date, however, thermotherapy in chronic
low back pain is not explicitly recommended in international guidelines. The
effects of thermotherapy on biomechanical parameters within a multimodal back
pain treatment concept are also unknown. METHODS: Within a multimodal treatment
concept, 176 patients with chronic low back pain were treated either with or
without supplemental heat wrap therapy. The range of movement and strength
parameters of the trunk in flexion, extension, lateral flexion and rotation were
measured before and after 12 weeks of treatment. FINDINGS: The range of movement
as well as strength parameters of the trunk improved on average within the
multimodal treatment. Patients receiving additional thermotherapy supplemental to
basic multimodal treatment showed a further improvement of strength parameters
regarding extension (P = 0.09, 1 - beta = 0.41), rotation to the right (P = 0.09,
1 - beta = 0.41) and rotation to the left (P = 0.08, 1 - beta = 0.42) in
comparison to those conducting only the multimodal treatment. No group
differences were detected in flexibility. INTERPRETATION: The implementation of
thermotherapy for several hours a day (heat wrap therapy) in daily clinical
practice additional to an individualized, evidence-based multimodal treatment
concept can be recommended to enhance strength parameters. The potential causes
of improved strength parameters as well as the meaning for the patients in
activity of daily living are discussed.
PMID- 29966959
TI - Asymmetrical loading during sit-to-stand movement in patients 1 year after total
hip arthroplasty.
AB - BACKGROUND: Asymmetrical loading during functional performance can occur after
total hip arthroplasty. We hypothesized that during sit-to-stand movements, the
loading of the limbs of patients who undergo total hip arthroplasty is more
asymmetrical than that of those who do not. The objective of the present study
was to compare asymmetrical loading during the sit-to-stand movements of patients
at 1 year after undergoing total hip arthroplasty, and that of healthy adults.
METHODS: Twenty-eight patients at 1 year after undergoing total hip arthroplasty
and 16 healthy adults were included. We measured the vertical ground reaction
force during the sit-to-stand movement for each leg and calculated the ratio of
the peak vertical ground reaction force, and the ratio at the time of peak
magnitude of the non-operated limb (control, right limb). FINDINGS: The mean peak
vertical ground reaction force ratio of the patients was 0.77 (0.2), and it was
significantly lower than that of healthy adults. The vertical ground reaction
force ratio for these patients at the time of peak magnitude of the non-operated
limb was 0.72 (0.2), and was significantly lower than that of healthy adults.
INTERPRETATION: Loading on the operated leg during the sit-to-stand movement was
lower than that on the non-operated leg in patients at 1 year after undergoing
total hip arthroplasty. Furthermore, loading during sit-to-stand movement of
patients 1 year after undergoing total hip arthroplasty was more asymmetrical
than that of healthy adults. Even at 1 year after undergoing total hip
arthroplasty, these patients performed the sit-to-stand movement asymmetrically.
PMID- 29966960
TI - Gait alterations on irregular surface in people with Parkinson's disease.
AB - BACKGROUND: Persons with Parkinson's disease are at high risk for fall-related
injuries with a large proportion of falls occurring while walking, especially
when the walking environments are complex. The aim of this study was to
characterize gait parameters on irregular surface for persons with Parkinson's
disease. METHODS: Three-dimensional gait analysis was conducted for nine persons
with Parkinson's disease and nine healthy age-matched adults on both regular and
irregular surfaces. Repeated ANOVA and paired t-test were performed to determine
the effect of surface and group for spatiotemporal, kinematic and stability
variables. FINDINGS: Individuals with Parkinson's disease showed a larger ratio
of reduction for speed, cadence and step length than controls when the surface
changed from regular to irregular. The ankle transverse range of motion and root
mean square of trunk acceleration increased on irregular surface for both groups.
Additionally, individuals with Parkinson's disease demonstrated a decreased knee
sagittal range of motion and trunk frontal and transverse range of motion
compared with controls, especially on the irregular surface. INTERPRETATION: The
irregular surface posed a greater challenge to maintain balance and stability for
individuals with Parkinson's disease. A relatively small knee range of motion in
the sagittal plane and large root mean square of trunk acceleration increased the
potential fall risk for individuals with Parkinson's disease. This information
improves the understanding of parkinsonian gait adaptations on irregular surfaces
and may guide gait training and rehabilitation interventions for this high fall
risk population.
PMID- 29966961
TI - Bilateral compensatory postural adjustments to a unilateral perturbation in
subjects with chronic ankle instability.
AB - BACKGROUND: To evaluate the magnitude of bilateral compensatory postural
adjustments in response to a unilateral sudden inversion perturbation in subjects
with chronic ankle instability. METHODS: 24 athletes with chronic ankle
instability (14 with functional ankle instability, 10 with mechanical ankle
instability) and twenty controls participated in this study. The bilateral
electromyography of ankle muscles was collected during a unilateral sudden ankle
inversion to assess the magnitude of subcortical and voluntary compensatory
postural adjustments in both the perturbed and the contralateral limb (support
limb). FINDINGS: In the support position, compared to the control group, the
group with functional ankle instability presented decreased compensatory postural
adjustments of the tibialis anterior in both the injured and the uninjured limbs
in the support position and of the soleus in the uninjured limb. In the side of
the perturbation, participants with functional ankle instability presented
decreased soleus compensatory postural adjustments in the uninjured limb when
compared to the control group. Increased values of soleus and peroneal brevis
compensatory postural adjustments were observed in the group with mechanical
instability when compared to the control group and to the group with functional
ankle instability. INTERPRETATION: Subjects with functional ankle instability
present bilateral impairment of compensatory postural adjustments of the tibialis
anterior in a support position and of the soleus of the uninjured limb regardless
of the position. Subjects with mechanical instability present bilateral increase
of these adjustments in the peroneal brevis regardless of the position and in the
soleus muscle in the side of the perturbation.
PMID- 29966962
TI - Relationship between the inflammatory tumor microenvironment and different
histologic types of canine mammary tumors.
AB - Mammary neoplasms are the tumors with higher incidence in female dogs. Among the
factors that contribute for the development of this and other neoplasms, the
inflammatory tumor microenvironment plays a crucial role. Several studies
reported important roles for lymphocytes, macrophages, plasma cells, neutrophils,
eosinophils and mast cells in this context. In the present study, our aim was to
evaluate the number of profile cells of inflammatory cells and area of tumor
fibrosis and the relation of these features with canine mammary tumors of
different histologic and clinical presentation (benign mixed tumor, carcinoma in
mixed tumor, solid carcinoma and tubular carcinoma) Counting and staining of
inflammatory cells and tumor fibrosis were performed through histochemistry,
while counting and staining of CD4+, TCD8+ and FOXP3+ lymphocytes were performed
through immunohistochemistry. Statistical analysis of the association between
densities of inflammatory cells, tumor fibrosis and histologic types revealed
significant difference for plasma cells (p = .035), neutrophils (p = .0113),
macrophages (p = .0047), and tumor fibrosis (p = .05). The found data suggest
associations between high number of neutrophils and aggressive mammary tumors,
between high densities of plasma cells, macrophages and CD8+ cells and between
low number of profile cells of CD4+ cells and less aggressive tumors. Larger
areas of tumor fibrosis showed relation to more aggressive canine mammary tumors.
PMID- 29966963
TI - Sex differences in affect-triggered lapses during smoking cessation: A daily
diary study.
AB - INTRODUCTION: Smoking lapses during a cessation attempt are common and are
thought to be a key predictor of full relapse. Positive and negative affective
states have been hypothesized as important precipitants of lapses during quit
attempts, although findings have been mixed. Accumulating evidence suggests that
women may smoke more when experiencing negative affective states, while men may
smoke more when experiencing positive affective states. The possibility that
these sex differences may play a role in predicting lapses during a smoking
cessation attempt, however, has not been well-investigated. In this study, we
hypothesized that, during a quit attempt, negative affect would be more strongly
associated with lapses among women, and positive affect would be more strongly
associated with lapses among men. METHOD: We conducted a prospective study in
which male and female nicotine-dependent smokers (n = 60) made an unaided, 'cold
turkey' quit attempt. For fourteen days following the initiation of the quit
attempt, participants completed daily diaries in which they recorded the degree
to which states of 'good mood' and 'bad mood' preceded smoking lapses. RESULTS:
Consistent with the study hypothesis, findings indicated that men reported higher
good-mood-induced smoking lapses than women across the 14-day study interval.
Conversely, while levels of bad-mood-induced smoking subsided over the 14-day
interval among men, levels persisted among women. DISCUSSION: Results further
underscore the need to address sex-specific affective triggers when developing
smoking cessation strategies.
PMID- 29966964
TI - A mediated multigroup model examining marijuana use consequences by sexual
orientation in us college students.
AB - Marijuana use holds a curvilinear relation to sexual orientation, whereby
bisexual individuals reporter higher frequency of use than exclusively hetero- or
homosexual individuals. This relation differs by gender, with more pronounced
differences among women. Bisexual individuals are at greater risk for negative
consequences of marijuana use, such as dependence. To mitigate potential risks,
individuals employ protective behavioral strategies (PBS). While differences in
use are known, research has yet to examine if consequences and PBS use vary by
sexual orientation. This study seeks to address the relations between sexual
orientation, consequences, gender, and PBS. It was hypothesized that orientation
would be associated with consequences, mediated by PBS, and these relations would
vary by gender. College students (N = 8141) from 11 different universities
completed an online survey measuring marijuana consequences, PBS use, and sexual
orientation. A final analytic sample (n = 2091) was composed of participants who
indicated past 30-day marijuana use (60% women, 64% White, mean age 19.92). Path
analysis was used to test all study hypothesis. Results indicated a curvilinear
relation between sexual orientation and consequences among men, however not
women. Moreover, PBS use mediated the relation between orientation and
consequences among men, and negatively predicted consequences among women.
Conclusions include that mixed sexual orientation men experience higher
consequences through lower PBS use. For women, PBS use buffers against
consequences. These findings reflect a general effectiveness of PBS use for
mitigating negative marijuana-related consequences. The implications of these
results are discussed.
PMID- 29966965
TI - Role of selenium and vitamin C in mitigating oxidative stress induced by
fenitrothion in rat liver.
AB - Excessive use of organophosphate insecticides, including fenitrothion (FNT) can
cause detrimental consequences in non-target organisms. Selenium (Se) and vitamin
C (Vit C) possess protective abilities against various toxic compounds due to
their antioxidative properties. Accordingly, the aim of the present study was to
examine the possible ameliorative effects of Se and Vit C in hepatotoxicity
induced by FNT. For the purpose of this study, male Wistar albino rats were
divided into control and groups treated with Se (0.5 mg/kg b.w, as Na2SeO3) and
Vit C (100 mg/kg b.w), FNT (20 mg/kg b.w) and FNT in cotreatment with Se and Vit
C for 30 days. The current data showed a reduction in absolute and relative liver
weight after FNT administration. Increased activities of liver enzymes (AST, ALT,
ALP, LDH and GGT) indicated liver damage. FNT alone caused significant
alterations in biochemical parameters (glucose and total bilirubin). Elevation in
LPO level along with decreased activities of antioxidant enzymes (SOD, CAT, GSH
Px) and GSH content reflected the presence of oxidative stress. Coadministration
of FNT with Se and Vit C exhibited hepatoprotective role confirmed by reduction
of oxidative stress levels and restoration in the values of examined parameters.
Because of their beneficial effects, Se and Vit C may be used in reducing
injuries caused by pesticides.
PMID- 29966966
TI - Application of sesquiterpene lactone: A new promising way for cancer therapy
based on anticancer activity.
AB - Cancer is one of the most dangerous diseases that are rapidly increasing
globally. After heart disease, it is the second leading cause of death,
accounting for seven million deaths each year. Chemotherapy is the use of
cytotoxic drugs on cancer cells. But the use of common chemotherapy drugs poses a
problem due their high side effects and low efficacy. As a result, efforts are on
to find new potent compounds with low side effects. The compounds extracted from
plants have been studied in this regard due to their prevalence. Sesquiterpene
lactones are a group of natural compounds that were first detected in Asteraceae
dark plants. These compounds exercise their effects by reacting with functional
groups available on proteins and enzymes, especially the thiol group. Owing to
the high side effects as an antitumor synthetic drugs, efforts are being made to
find drugs with high efficiency and low side effects. Their high structural
ranges have attracted the attention of many researchers as a potential source of
new anticancer drugs.
PMID- 29966967
TI - Conditioned medium from stimulated macrophages inhibits growth but induces an
inflammatory phenotype in breast cancer cells.
AB - Disparate roles exist for tumor-associated macrophages in breast cancer growth
and progression. The aim of this study was to explore the influence of induced
macrophages on the growth of breast cancer cells. THP-1 monocytes were
differentiated to macrophages using phorbol 12-myristate 13-acetate. The effect
of the medium from THP-1 monocytes or macrophage-conditioned medium (MphiCM) on
MCF-7 (estrogen receptor and progesterone-positive positive) and MDA-MB-231 (MB;
triple-negative) breast cancer cells was determined at 24 h, 48 h and 72 h.
Assays were conducted for cell viability, apoptosis, proliferation and cell
phenotype, and quantitative real-time polymerase chain reaction (qRT-PCR) for
expression of associated genes. MphiCM inhibited proliferation of MCF-7 and MB
cells in a time-dependent manner and, in particular, decreased viability of MCF-7
cells. MphiCM induced a markedly vacuolated phenotype in MCF-7 increased
apoptosis in MCF-7 cells, but correlative changes in Bcl-2 or Bax were absent. A
multifold and significant reduction in anti-apoptotic Bcl-2 in MB cells was not
matched by increased apoptosis. The cell cycle inhibitor CDKN1A was increased in
both cell lines, but PCNA decreased only in MB cells. Senescence-associated
galactosidase beta-1 (GLB1) mRNA was decreased in MCF-7 cells (48 and 72 h) but
increased in MB cells (72 h). Increased expression of interleukin-6 (IL-6) and IL
8 was seen in both cell lines, and increased tumor necrosis factor- alpha was
seen at 24 h for MB and 72 h for MCF-7 indicating increased inflammatory
responses of the cancer cells. The two breast cancer celllines had different
responses to MphiCM, mainly involving inhibition rather than stimulation of
growth of the cells, stimulation of senescence (MB cells) and increased
inflammatory cytokine expression. The estrogen and progesterone receptor status
of the cell lines may determine their response to MphiCM. The function of the
inflammatory cytokines in breast cancer growth remains to be identified.
PMID- 29966968
TI - Paeoniflorin inhibits Rho kinase activation in joint synovial tissues of rats
with collagen-induced rheumatoid arthritis.
AB - Paeoniflorin (PF) has many effects, such as anti-inflammation, immune-regulation,
abirritation, and so on. However, the protective mechanisms of PF on rheumatoid
arthritis (RA) was not completely known. Thus, we explored deeply the protective
mechanisms in a collagen-induced RA (CIA) rat model. CIA was induced in rats by
intradermal injection of bovine type II collagen in complete Freund's adjuvant.
Later, the CIA rats received oral administration of PF (50 and 100 mg/kg) once a
day from the day 21, with the treatment lasting for 14 days. A variety of
indicators were measured for evaluation of anti-rheumatism effect, including paw
swelling, arthritis scores, and histopathological changes. And the contents of
pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha),
interleukin-1 beta (IL-1beta), and interleukin-6 (IL-6) in the serum, as well as
p-NF-kappaB p65 and p-MYPT1 in the joint synovial tissues were detected to
explore the possible mechanisms. The results demonstrated that PF treatment
significantly ameliorated the symptoms in CIA rats, reduced the levels of pro
inflammatory cytokines and paw swelling, down-regulated the expressions of p-NF
kappaB p65 and p-MYPT1. The present results revealed that PF could effectively
improve collagen-induced RA in rats by inhibiting Rho kinase activation in the
joint synovial tissues, in turn down-regulating expression of p-NF-kappaB p65 and
reducing contents of pro-inflammatory cytokines. Moreover, PF may be an effective
agent for RA.
PMID- 29966969
TI - Enhanced expression of lncRNA TP73-AS1 predicts adverse phenotypes for
cholangiocarcinoma and exerts oncogenic properties in vitro and in vivo.
AB - Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with
increasing incidence worldwide. Various evidence documents that abnormally
expressed long non-coding RNAs (lncRNAs) play important roles in tumorigenesis
and progression. TP73-AS1 is a novel cancer-related lncRNA that contributes to
the development of several malignancies. However, its clinical value and
potential effects on CCA remains unknown. RT-qPCR was used to measure the
expression levels of TP73-AS1 in CCA tissues and paired non-tumor tissues and the
association between TP73-AS1 expression and clinicopathological characteristics
was analyzed. In addition, the functional roles of TP73-AS1 in CCA were detected
both in vitro and in vivo. The results illustrated that TP73-AS1 transcription is
enhanced in both CCA tissue samples and cell lines, and this upregulation is
closely associated with larger tumor size (p=0.008) and advanced TNM stage
(p=0.026) in patients with CCA. For the part of functional assays, silencing of
TP73-AS1 could attenuate CCA cell growth both in vitro and in vivo. Additionally,
silencing of TP73-AS1 facilitates apoptosis via activating caspase-3 and caspase
9. Importantly, TP73-AS1 expression did not affect HIBEC cell growth and
apoptosis. Moreover, TP73-AS1 could also facilitate migration and invasion
potential of CCA cells. Collectively, these findings may help to develop a
potential therapeutic target for the patients with CCA.
PMID- 29966970
TI - Down-regulated miR-148b increases resistance to CHOP in diffuse large B-cell
lymphoma cells by rescuing Ezrin.
AB - BACKGROUND: Aberrant microRNA (miRNAs) have recently been proposed as important
regulators in acquiring resistance to cyclophosphamide, doxorubicin, vincristine,
and prednisone (CHOP) in diffuse large B-cell lymphoma (DLBCL). The purpose of
this study was to establish the role of miR-148b in the development of CHOP
resistance in DLBCL. METHODS: The expression patterns of miR-148b, HDAC6, and
Ezrin were detected in CHOP-resistant clinical specimens and a DLBCL cell line.
miR-148b, HDAC6, and Ezrin in DLBCL cells were manipulated by cell transfection
to explore the functional correlation between them. Cell viability was determined
using a CCK-8 assay. RESULTS: We found that miR-148b levels were markedly reduced
and that the protein expressions of HDAC6 and Ezrin were increased in DLBCL CHOP
resistant clinical specimens and the cell line CRL2631/CHOP. Indeed, HDAC6
decreased the acetylation of histones H3 and H4 in the miR-148b promoter to
inhibit miR-148b expression in DLBCL. Moreover, down-regulated miR-148b
encouraged CHOP resistance in CRL2631 cells and miR-148b sensitized CRL2631
cells. We further revealed that Ezrin was negatively regulated by miR-148b and
that the knockdown of Ezrin significantly attenuated CHOP resistance in CRL2631
cells induced by miR-148b silencing. MiR-148b also sensitized CRL2631/CHOP cell
xenografts to CHOP in mice. CONCLUSION: Our data indicated that the high level of
HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and
H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP
resistance in DLBCL.
PMID- 29966971
TI - RGD peptide-modified, paclitaxel prodrug-based, dual-drugs loaded, and redox
sensitive lipid-polymer nanoparticles for the enhanced lung cancer therapy.
AB - One approach to improve the targeted therapeutic efficiency of lung cancer is to
deliver drugs using nano-scaled systems. In this study, RGD peptide-modified,
paclitaxel (PTX) prodrug-based, dual-drugs loaded, and redox-sensitive lipid
polymer nanoparticles were developed and the in vitro and in vivo antitumor
efficiency was evaluated in lung cancer cells and tumor bearing animal models.
RGD-modified PTX and cisplatin (CDDP) loaded LPNs (RGD-ss-PTX/CDDP LPNs) have
sizes around 190 nm, and zeta potentials of -35 mV. The half-maximal inhibitory
concentration (IC50) values were 26.7 and 75.3 MUg/mL for drugs loaded LPNs and
free drugs combination, which indicates significantly higher antitumor activity
of LPNs than free drugs. RGD-ss-PTX/CDDP LPNs also exhibited the best antitumor
efficiency in vivo, which inhibited the tumor size of mice from 1486 mm3 to 263
mm3. The results illustrated that the system could successfully load drugs and
achieve synergistic combination lung cancer treatment efficiency with lower
systemic toxicity compared with free drugs counterparts. The resulting system
could be facilitated as a promising targeted nanomedicine for the treatment of
lung cancer.
PMID- 29966972
TI - Biochemical investigation of gender-specific association between insulin
resistance and inflammatory biomarkers in types 2 diabetic patients.
AB - Inflammatory mediators play a key role in the pathogenesis of type 2 diabetes
mellitus (T2DM) and development of insulin resistance (IR). The purpose of the
present study was to investigate the gender-specific association between serum
levels of inflammatory biomarkers and development of IR in type 2 diabetic
patients. We recruited 90 study participants and collected their blood samples to
measure the serum level of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF
alpha), C-reactive protein (CRP), insulin and glucose. We found that the serum
levels of IL-6 (< 0.0001), TNF-alpha (< 0.0001) and CRP (< 0.0001) in type 2
diabetic patients were significantly high as compared to control participants.
Moreover, we also found that in female diabetic patients, a significant
association was observed between the elevated levels of IL-6 (r = 0.8819, R2 =
0.7778), TNF-alpha (r = 0.9833, R2 = 0.9669) and CRP (r = 0.9529, R2 = 0.9080)
and increased risk of developing IR when compared with that of the serum levels
of IL-6 (r = 0.7977, R2 = 0.6364), TNF-alpha (r = 0.9445, R2 = 0.8920) and CRP (r
= 0.9051, R2 = 0.8192) of male diabetic patients. Additionally, we also found
that the Body mass index (BMI) of female diabetic patients was strongly
correlated (r = 0.9694, R2 = 0.9398) with the increased incidence of IR as
compared to that of the BMI (r = 0.9188, R2 = 0.8442) of male diabetic patients.
The key findings of present study exhibit that gender differences significantly
influence the association of inflammatory biomarkers with the development of IR
in T2DM.
PMID- 29966973
TI - Anticancer effect of the water extract of a commercial Spirulina (Arthrospira
platensis) product on the human lung cancer A549 cell line.
AB - Spirulina is a well-described and popular dietary supplement derived from
Arthrospira algae. In the present study, the anticancer potential of a water
extract of a commercial Spirulina product (SE) against the human non-small-cell
lung carcinoma A549 cell line was evaluated. After qualitative analysis, we
investigated the effect of SE on cell viability, proliferation, and morphology.
Furthermore, the influence of SE on regulation of the cell cycle, induction of
apoptosis in lung cancer cells, and expression of cell cycle/apoptosis-related
proteins was evaluated. Additionally, we examined the cytotoxic effect of SE on
normal human skin fibroblasts (HSF). Our studies revealed that SE significantly
reduced cancer cell viability and proliferation, which was accompanied by cell
cycle inhibition in the G1 phase, induction of apoptosis, and prominent
morphological changes. Moreover, we detected no cytotoxic effect of the tested
Spirulina extract on normal skin fibroblasts. Our molecular studies demonstrated
that SE reduced the phosphorylation of Akt and Rb proteins, reduced the
expression of cyclin D1 and CDK4, and increased the Bax to Bcl-2 ratio in the
A549 cells. In conclusion, the results obtained provide evidence of the anti
cancer activity of the commercial Spirulina product against lung cancer cells and
strongly support the knowledge of the chemopreventive properties of Spirulina.
PMID- 29966974
TI - Effect of interleukin-6 on myocardial regeneration in mice after cardiac injury.
AB - Our aim was to investigate the role of interleukin-6 (IL-6) in myocardial
regeneration from mice after cardiac injury. The newborn mice were divided into
the following 4 groups (16 in each group): sham group, model group, IL-6-/- group
(IL-6 knockout) and IL-6 group (IL-6 overexpression). Electrocardiography was
performed on all mice and found higher LVEDD, LVESD and IVST and lower LVEF and
LVFS in the IL-6 group compared with the sham group. Using HE staining, severe
myocardial injury combined with infarction and fibrosis were observed in the IL-6
/- group, while the damaged myocardial tissue was repaired to some extent in the
IL-6 group. The expression of IL-6 in the IL-6 group were significantly up
regulated. BrdU immunofluorescence found that the IL-6-/- group had the least
number of BrdU positive cells, while the IL-6 group had more BrdU positive cells
than the model group and the IL-6-/- group. Expressions of IL-6, cyclinD1 and Bcl
2 in the IL-6 group were up-regulated compared with other groups. In conclusion,
IL-6 overexpression could enhance cardiomyocyte proliferation and relevant
protein expression in mice myocardium, thus promoting cardiac regeneration.
PMID- 29966975
TI - HUWE1 upregulation has tumor suppressive effect in human prostate cancer cell
lines through c-Myc.
AB - PURPOSE: We investigated the regulatory function of HECT, UBA and WWE domain
containing protein 1, E3 ubiquitin protein ligase (HUWE1) in human prostate
cancer (CaP). METHODS: HUWE1 was overexpressed (through transfection) or
downregulated (through lentiviral transduction) in CaP cell lines, PC3 and DU145
cells. The functions of HUWE1 overexpression or downregulation on CaP cancer cell
proliferation, migrationin vitro, and explant in vivo were examined. In addition,
the regulatory effect of HUWE1 on c-Myc expression was assessed. In HUWE1
overexpressed CaP cells, c-Myc was further upregulated to assess whether c-Myc
was directly involved in HUWE1-induced regulation in CaP. RESULTS: HUWE1
overexpression inhibited CaP proliferation and migrationin vitro, and explant
growth in vivo. On the other hand, HUWE1 downregulation had no effects on CaP in
vitro. C-Myc was downregulated in HUWE1-overexpressed, but un-changed in HUWE1
downregulated, CaP cells. Further upregulating c-Myc in HUWE1-overexpressed CaP
cells reversed the tumor-suppressing effects by HUWE1-overexpression on cancer
proliferation and migration in vitro. CONCLUSION: HUWE1 overexpression could
functionally suppress CaP development bothin vitro and in vivo, possibly by
inverse regulation on c-Myc.
PMID- 29966977
TI - Effect of herbal mixture composed of Alchemilla vulgaris and Mimosa on wound
healing process.
AB - Alchemilla vulgaris and Mimosa tenuiflora (Mimosa) have been used to treat
cutaneous wounds as a traditional remedy due to their various biological
activities. But, there are only a few studies about the effects of these herbs on
wound healing. The purpose of this study is to investigate the wound healing
effect of the herbal mixture, consisting of A. vulgaris and Mimosa, in mice and
to determine the activity of the extract in vitro. In present study, application
of an ointment containing the herbal mixture on the dorsal skin wounds of mice
showed that the wound healing process was faster than treatment of Fusidic acid.
Histological analysis demonstrated the herbal mixture promoted re
epithelialization, collagen synthesis, and especially the regeneration of skin
appendages such as hair follicles. Immunohistochemical analysis revealed the
herbal mixture improved angiogenesis and the stabilization of blood vessels, as
well as accelerated the formation of granulation tissue. In addition, we
demonstrated that herbal mixture enhanced the migration of HaCaT, fibroblasts,
and HUVECs on a two-dimensional wound, and promoted the proliferation of
macrophages and lymphatic vessels. Our results demonstrated that herbal mixture
can promote the migration of keratinocytes, fibroblasts, and endothelial cells,
and the proliferation of macrophages and lymphatic vessels. Furthermore, it
showed that herbal mixture accelerates wound healing. Therefore, we suggest that
herbal mixture may have a potential for therapeutic use for treatment and
management of cutaneous wound.
PMID- 29966976
TI - Effects of multi and selective targeted tyrosine kinase inhibitors on function
and signaling of different bladder cancer cells.
AB - BACKGROUND: Signaling of receptor tyrosine kinases (RTK) is dysregulated in
various malignancies including bladder cancer. RTKs trigger pro-proliferative,
anti-apoptotic and metastatic signaling pathways. Here, we assessed the effects
of a selective tyrosine kinase inhibitor (TKI) (BGJ398) targeting fibroblast
growth factor receptor (FGFR) and a pan-TKI (TKI258) targeting (FGFR), platelet
derived growth factor receptor (PDGFR) and vascular endothelial growth factor
receptor (VEGFR) in bladder cancer cells. METHODS: Levels of mRNA transcripts
were measured in nine human cell lines by quantitative RT-PCR. Cell function was
assessed for viability, colony formation, migration, apoptosis and proliferation.
Protein mediators of signal transduction were measured by Western-blot. RESULTS:
mRNA transcripts encoding RTK-related components, transcription factors,
epithelial and mesenchymal transition (EMT) markers as well as cell cycle and
apoptotic factors were determined in the cell lines. Principal component analysis
ordered one epithelial-like cell cluster (5637, BFTC-905, MGHU4, RT112) and one
mesenchymal-like cell cluster (T24, UMUC3, HU456, TCC-SUP). Cell response scores
towards TKI258 and BGJ398 treatment were heterogeneous between cell lines and
correlated with certain transcript levels. Analysis of signal transduction
pathways revealed inhibition of fibroblast growth factor receptor (FGFR)
signaling and induction of cell cycle dependent kinase (CDKN1A, p21) in
epithelial-like cells differing in this regard from responses to mesenchymal-like
cells that exhibited inhibition of mitogen-activated protein kinase (MAPK).
CONCLUSION: RTK and EMT related transcript analysis separate bladder cancer cells
in two clusters. Functional responses towards TKI258 and BGJ398 treatment of
bladder Fcancer cells were heterogeneous with deviating effects on signaling and
possibly different therapeutic outcome.
PMID- 29966978
TI - Silencing of PINK1 represses cell growth, migration and induces apoptosis of lung
cancer cells.
AB - PTEN induced putative kinase 1 (PINK1) has been found to be up-regulated, which
promotes the proliferation and chemoresistance in lung cancer. Nevertheless, the
role and detailed mechnisms of PINK1 in lung cancer have not been fully
understood, which need to be further clarified. In this study, the resluts showed
that silencing of PINK1 inhibited proliferation and blocked cell cycle of lung
cancer cells. Furthermore, the apoptosis rate was enhanced by PINK1 suppression,
as evidenced by increased protein levels of Bax, cleaved caspase-3 and cleaved
poly (ADP-ribose) polymerase (PARP), and decreased level of Bcl-2. The migration
and invasion abilities were also restrained by PINK1 silencing. Silencing of
PINK1 also resulted in oxygen species (ROS) overproduction and decreased
mitochondrial membrane potential. Finally, suppression of PINK1 repressed the
growth of xenograft tumor and induced apoptosis in tumor tissues in vivo. This
study might lead to PINK1 kinase as a novel therapeutic target for lung cancer
treatment.
PMID- 29966979
TI - Calycosin inhibits nasopharyngeal carcinoma cells by influencing EWSAT1
expression to regulate the TRAF6-related pathways.
AB - The incidence of nasopharyngeal carcinoma (NPC) in China is relatively higher
than that throughout the rest of the world, and NPC is geographically
distributed. Long non-coding RNA (lncRNA) plays a key role in the development of
tumors. Recent studies have found that the lncRNA Ewing sarcoma-associated
transcript 1 (EWSAT1) is highly expressed in various tumors and also in NPCs. The
isoflavone calycosin, which is a typical Chinese herbal medicine, can inhibit the
growth of breast cancer, colorectal cancer, osteosarcoma and other cancers. The
aim of our study was to select NPCs that were sensitive to calycosin and whether
calycosin had an effect on NPC cells. If it does, are the effects related to a
high expression of EWSAT1? We also verified that EWSAT1 was highly expressed in
NPC cells. At the same time, we found that calycosin inhibited the growth of NPC
cell lines. To further determine whether the effect of calycosin on NPC cells was
related to EWSAT1, we used NPC cells with different concentrations of calycosin
and found that the expression of EWSAT1 decreased significantly with increasing
concentrations of calycosin and that the expression of downstream factors and
pathways were also affected. It was demonstrated that calycosin affected NPC cell
growth by regulating EWSAT1 and its downstream pathway. In addition, we
overexpressed EWSAT1 and found that the increased expression of EWSAT1 weakened
the growth inhibitory effect of calycosin on NPC cells.
PMID- 29966980
TI - Neuroprotective effect of formononetin against TBI in rats via suppressing
inflammatory reaction in cortical neurons.
AB - Traumatic brain injury (TBI) refers to external force-induced brain damage,
characterized with necrosis and cell loss in cerebral cortex. Interestingly, a
plant-extract named formononetin (FN) is found to possess promising
pharmacological activities, including cellular neuroprotection. Thus, we propose
that FN may exert biological protection against TBI and discuss the underlying
mechanism. In the current study, a rat TBI model was established via Feeney's
classical method, followed by different concentrations of FN treatment. Nissl
special and DAPI-labeled stains were utilized to assess the proliferation of
cortical neurons nearing lesioned tissue. The contents of interleukin-6 (IL6),
tumor necrosis factor (TNF-alpha), and interleukin-10 (IL10) in serum and the
cortical neurons were determined by ELISA. Further, intracephalic IL10 expression
levels were detected through immunoassay and RT-PCR. Interestingly, the results
exhibited within the FN-treated TBI rat model indicated elevated cortical
proliferation. The levels of IL10 in serum and the cortical neurons were
increased following FN treatments, while TNF-alpha and IL6 levels in the blood
were decreased. In addition, both mRNA and protein expression levels of IL10 in
the FN-treated TBI rat model were up-regulated in a dose-dependent manner.
Collectively, our present findings indicate that FN provides effective
neuroprotection against TBI, likely by activating IL10 expression in cortical
neurons nearing lesioned tissue to inhibit neuroinflammatory reaction.
PMID- 29966981
TI - Heshouwu (Polygonum multiflorum Thunb.) ethanol extract suppresses pre-adipocytes
differentiation in 3T3-L1 cells and adiposity in obese mice.
AB - This study investigated whether Heshouwu (Polygonum multiflorum Thunb.) root
ethanol extract (PME) has anti-obesity activity using 3T3-L1 cells and high-fat
diet (HFD)-induced obese mice. Treatment with PME (5 and 10 MUg/mL) dose
dependently suppressed 3T3-L1 pre-adipocyte differentiation to adipocytes and
cellular triglyceride contents. In addition, PME inhibited mRNA and protein
expression of adipogenic transcription factors such as CCAAT/enhancer-binding
protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma
(PPARgamma), which led to down-regulation of fatty acid synthase gene expression.
After feeding mice PME (0.05%) with HFD for 12 weeks, their visceral fat mass,
size and body weight were significantly reduced compared with the HFD group.
Furthermore, PME supplementation significantly up-regulated the PPARalpha, CPT1,
CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down
regulated expression of the PPARgamma and DGAT2 genes. Finally, HFD increased
serum leptin, insulin, glucose and insulin and glucose levels; however, PME
reversed these changes. These results demonstrated that PME might relieve obesity
that occurs via inhibition of adipogenesis and lipogenesis as well as through
lipolysis and fatty acid oxidation in 3T3-L1 cells and HFD-induced obese mice.
PMID- 29966982
TI - Evidence of hypoglycemic, lipid-lowering and hepatoprotective effects of the
Bixin and Bixin: beta-CD inclusion compound in high-fat-fed obese mice.
AB - Associations between obesity, diabetes type II, and steatosis have long been
recognized. However, a pharmacotherapy that acts in a multifactorial manner
controlling the interactions between these conditions is not available. A variety
of natural plants, functional fatty acids, and other natural dietary compounds
have been used in various anti-obesity products. We investigated the effects of
oral administration of an antioxidant carotenoid pigment Bixin and Bixin: beta
Cyclodextrin in an obese murine model. C57BL/6 male mice (4-5 weeks) received
standard diet (2.18 kcal per 1 g) (CT) and high-fat diet (4.38 kcal per 1 g)
(CT/OB, BIX and BIX/betaCD) (n = 10 per group). After 16 weeks, the BIX and
BIX/betaCD were treated by gavage (100 MUL day-1) for six weeks, with water (CT
and CT/OB groups) and (50 mg kg-1 day-1), Bixin (BIX group) or Bix: beta-CD
(BIX/betaCD). Body weight, Lee's Index, adiposity, CHT, TG, CHT/HDL-c, glucose
levels (metabolic markers) and, liver markers (AST and ALT) were determined. All
metabolic and liver parameters exhibited down-regulation after oral
administration of BIX and BIX/betaCD. Particularly relevant was Lee's Index and
adiposity in BIX- and BIX/betaCD-treated groups (339.18 g/cm -BIX and 327.58 g/cm
-BIX/betaCD vs. 360.68 g/cm -CT/OB animals), this finds associated with the
insulin sensitivity test, showed a clear association between reduction of adipose
tissue and decrease of peripherical insulin resistant. In conclusion, our study
suggested that the oral administration of the Bixin and Bix: beta-CD inclusion
compound improved the metabolic parameters evaluate in obese mice, being more
palatable and hepatoprotective.
PMID- 29966983
TI - Apigenin suppresses mouse peritoneal fibrosis by down-regulating miR34a
expression.
AB - Peritoneal fibrosis is a severe side-effect of chronic peritoneal dialysis in
patients with end-stage renal disease, but not enough effective therapeutic drugs
are currently available in clinics. The aim of this study was to evaluate the
effects of apigenin and miRNA on the progression of peritoneal fibrosis. We
treated isolated mouse mesothelial peritoneal cells (MMCs) with high glucose
(HG), to induce fibrosis. We used qRT-PCR and Western blotting to measure the
expressions of multiple epithelial-mesenchymal transition (EMT) biomarkers, like
E-cadherin, transcription termination factor (TTF), N-cadherin and vimentin, as
well as several apoptosis and autophagy biomarkers. We determined the IC50 of
apigenin on MMC fibrosis. We also used qRT-PCR to assess the expressions of
miRNAs in MMC fibrosis. In addition, we by used the CCK8 assay, Hoechest staining
and flow cytometry, to measure cell viability and proliferation rates. We
successfully induced fibrosis using high glucose (HG) treatment in MMCs. This was
further validated by the observed changes in E-cadherin, TTF, N-cadherin and
vimentin expression levels. We also observed highly elevated expression levels of
miR34a during HG-induced MMC fibrosis. Apigenin treatment induced a significant
decrease in miR34a expression levels in HG-treated MMCs. Moreover, both apigenin
treatment and miR34a depletion, as well as their combination, significantly
promoted proliferation and suppressed apoptosis of MMCs treated with high
glucose. This was accompanied with a corresponding alteration in expressions of
EMT, apoptosis and autophagy biomarkers. In summary, apigenin effectively
inhibits mouse mesothelial peritoneal cell fibrosis induced by high glucose, and
this is, at least partially mediated by the suppression of miR34a expression.
PMID- 29966984
TI - Ginger alleviates hyperglycemia-induced oxidative stress, inflammation and
apoptosis and protects rats against diabetic nephropathy.
AB - Oxidative stress plays a major role in the development and progression of
diabetic nephropathy (DN). In this study, the potential protective effect of
ginger (Zingiber officinale) rhizome extract on hyperglycemia-induced oxidative
stress, inflammation and apoptosis was investigated. An experimental diabetic rat
model was induced by intraperitoneal injection of streptozotocin. Diabetic rats
were treated orally with 400 or 800 mg/kg/day Z. officinale extract for six
weeks. Diabetic animals exhibited elevated blood glucose levels and glycated
hemoglobin (HbA1c) with altered lipid profile. Blood urea nitrogen, serum
creatinine and urea, and urine albumin levels were significantly increased in
diabetic rats. Treatment with Z. officinale ameliorated hyperglycemia,
hyperlipidemia and kidney function. In addition, Z. officinale minimized the
histological alterations in the kidney of diabetic rats. Chronic hyperglycemia
resulted in a significant increase in malondialdehyde, protein carbonyl, pro
inflammatory cytokines, cytochrome c and caspase-3 in the kidney of rats. Z.
officinale extract significantly attenuated oxidative stress, inflammation and
apoptosis, and enhanced antioxidant defenses in the diabetic kidney. In
conclusion, this study strongly suggests that Z. officinale rhizome extract
exerts a protective role against diabetes-induced renal injury by ameliorating
oxidative stress, inflammation and apoptosis.
PMID- 29966985
TI - Thymoquinone: A novel strategy to combat cancer: A review.
AB - The higher consumption of fruit, herbs, spices, and vegetables is well known and
practical strategy to cure human cancers owing to their presence of bioactive
compounds. Among these, Nigella sativa is a promising source of bioactive
compounds including thymoquinone, monoterpenes, p-cymene and alpha-piene etc.
Thymoquinone has been found effective to inhibit the different cancer stages such
as proliferation, migration and invasion. It also acts as anticancer agent
against different human cancers such as breast, pancreatic, prostate, blood,
oral, bone, head and neck, cervical, liver and lung. It significantly mediated
miR-34a up-regulation, enhanced the levels of miR-34a through p53, and down
controlled Rac1 expression. Thymoquinone induces apoptosis, regulates the levels
of pro- and anti- apoptotic genes. It also has been known to lower the
phosphorylation of NF-kappaB and IKKalpha/beta and reduces the metastasis as well
as also lowered the ERK1/2 and PI3K activities. Thymoquinone inhibits the
metastasis through activation of JNK and p38. The present review article
highlights the anticancer perspectives of thymoquinone in human by various
pathways and use of this compound as diet based therapy has proven new
pharmacological agent against several types of cancers.
PMID- 29966986
TI - In vitro combinatorial anti-proliferative and immunosuppressive effects of Brucea
javanica extract with CX-4945 and imatinib in human T-cell acute lymphoblastic
leukemia cells.
AB - Since 1970, the isolated and identified components of Brucea javanica (L.) Merr.
have been known to contain anticancer effects, particularly antileukemic effect.
In this study, the inhibitory effect of Brucea javanica (BJ) on cell growth and
inflammation was confirmed in human T-cell acute lymphocytic leukemia (T-ALL)
cells, and its efficacy as an antileukemic agent was verified. Our results showed
that BJ extract induced caspase-dependent apoptosis of T-ALL Jurkat cells through
inhibition of the CK2-mediated signaling pathway, while exerting no significant
cytotoxicity in normal peripheral blood mononuclear cells. Moreover, BJ extract
suppressed the NF-kappaB signaling pathway, thus, inhibiting the interleukin (IL)
2 expression induced by phorbol 12-myristate 13-acetate (PMA) and
phytohemagglutinin (PHA). Notably, combined treatment with BJ extract plus CX
4945 or imatinib exerted enhanced inhibitory effects on T-ALL cell growth and IL
2 production. Overall, these results suggest that BJ extract can be a potent
therapeutic herbal agent for T-ALL treatment and prevention of IL-2 mediated
inflammatory immune responses.
PMID- 29966987
TI - Synthesis and characterization of carboxymethyl chitosan/Fe3O4 and MnFe2O4
nanocomposites hydrogels for loading and release of curcumin.
AB - This paper presents the preparation of hydrogel with magnetic properties derived
from carboxymethyl chitosan for controlled drug release performance. The magnetic
Fe3O4 and MnFe2O4 nanoparticles with crosslinked Carboxymethyl Chitosan hydrogel
were prepared by using epichlorohydrin as the cross-linker. The structure
characterization performed by FT-IR. The XRD analysis was applied for evaluation
of crystalline phase of MnFe2O4 and Fe3O4 in the hydrogels. The crystallite size
of Fe3O4/CMCS and MnFe2O4/CMCS was calculated to be 30.12, and 44.51 nm,
respectively. The presence of MnFe2O4 and Fe3O4 in the hydrogels can reason a
rough surface morphology which that confirmed by SEM images. The Max. Saturation
magnetization value as obtained from hysteresis loop is 105 and 75 Am2/kg for
Fe3O4/CMCS and MnFe2O4/CMCS hydrogel, respectively. The Fe3O4 and MnFe2O4 on
Carboxymethyl Chitosan hydrogels indicated a pH-sensitive for swelling behavior
process. The equal amount of Fe3O4 and MnFe2O4 on hydrogels have high swelling at
pH 6.4. The swelling capacity decreased from 214 to 172% and 144-114% at pH 6.4
with attendance of high amount of MnFe2O4 and Fe3O4 on hydrogels compared to
other samples, respectively. Drug loading and release performances were
investigated by curcumin as a model drug. The maximum curcumin release was
obtained 25.1-51.52% at pH = 6.4. The drug releases system demonstrates the high
ratio of Fe3O4 and MnFe2O4 containing Carboxymethyl Chitosan sample has a great
efficiency in curcumin release. The effect of applied magnetic field on drug
release for Fe3O4/CMCS was highest compared to MnFe2O4/CMCS. The results
demonstrated that the Fe3O4 and MnFe2O4 nanocomposites hydrogel can be applied
for novel drug delivery systems.
PMID- 29966988
TI - Photodynamic activity of Temoporfin nanoparticles induces a shift to the M1-like
phenotype in M2-polarized macrophages.
AB - The monocyte/macrophage cell lineage reveals an enormous plasticity, which is
required for tissue homeostasis, but is also undermined in various disease
states, leading to a functional involvement of macrophages in major human
diseases such as atherosclerosis and cancer. We recently generated in vivo
evidence that crystalline, nonfluorescent nanoparticles of the hydrophobic
porphyrin-related photosensitizer Aluminum phthalocyanine are selectively
dissolved and thus may be used for specific fluorescent labelling of rejected,
but not of accepted xenotransplants. This led us to hypothesize that
nanoparticles made of planar photosensitizers such as porphyrins and chlorins
were preferentially taken up and dissolved by macrophages, which was verified by
in vitro studies. Here, using an in vitro system for macrophage
differentiation/polarization of the human monocyte THP-1 cell line, we
demonstrate differential uptake/dissolution of Temoporfin-derived nanoparticles
in polarized macrophages, which resulted in differential photosensitivity. More
importantly, low dose photodynamic sensitization using Temoporfin nanoparticles
can be used to trigger M1 re-polarization of THP-1 cells previously polarized to
the M2 state. Thus, sublethal photodynamic treatment using Temoporfin
nanoparticles might be applied to induce a phenotypic shift of tumor-associated
macrophages for the correction of an immunosuppressive microenvironment in the
treatment of cancer, which may synergize with immune checkpoint inhibition.
PMID- 29966989
TI - Detecting urine metabolites related to training performance in swimming athletes
by means of Raman spectroscopy and principal component analysis.
AB - Raman spectroscopy (RS) is a vibrational technique that is suitable for
performing biochemical analyses in human tissues and fluids. This work has
investigated the identification of biochemical markers due to physical
performance in the urine of swimming athletes. This was achieved by means of the
Raman features that were found before and after the swimming training compared to
the sedentary control subjects. These particular biochemical marker
identifications refer to and infer the physiological status of individuals. The
urine samples (single stream) were collected before and after the training
(velocity, middle distance and distance) of professional swimmers, as well as
from sedentary subjects (control). The urine samples were submitted to RS (830 nm
excitation, 350 mW, 400-1800 cm-1 spectral range, 4 cm-1 resolution) and the
spectra after the training were compared to the spectra before training, and
subsequently, to the control subjects. The principal component analysis (PCA) was
employed in order to identify the biochemicals that were responsible for the
spectral differences. The Raman features of the urine samples after training
showed peaks that were related to common urine metabolites, such as urea and
creatinine. PCA analysis also revealed Raman features that were attributed to
other metabolites, such as creatine, ketone bodies, phosphate and nitrogenous
compounds in the swimmers after training. RS was a rapid and reliable technique
for the evaluation of urine metabolites that were related to the physical
performance of high-level swimmers, which then allowed for an accurate assessment
and a control of their physiological efficiencies.
PMID- 29966990
TI - Control of the incorporation and release of guest molecules by photodimerization
in liposomes.
AB - In a drug-delivery system using liposomes, the use of guest molecules bearing
hydrophilic moieties results in some leakage from lipid membranes. We suppressed
the leakage of coumarins (used as model guest molecules in a drug-delivery
system) from lipid membranes by photodimerization at 365 nm. The reason for this
phenomenon could be ascribed to an increase in the hydrophobicity of the dimers
of the coumarins. The formation of the dimers was detected by 1H NMR, UV-vis
absorption, and mass spectra and the leakage percentages of the coumarins were
determined by 1H NMR spectra based on the peak intensities. In contrast, when the
dimer reverted to a monomer by ultraviolet (254 nm) irradiation, the resulting
monomer was released from liposomes.
PMID- 29966991
TI - Rubus idaeus L. (red raspberry) blocks UVB-induced MMP production and promotes
type I procollagen synthesis via inhibition of MAPK/AP-1, NF-kappabeta and
stimulation of TGF-beta/Smad, Nrf2 in normal human dermal fibroblasts.
AB - Chronic exposure to ultraviolet (UV) radiation causes photo-oxidation, which in
turn results in the upregulation of matrix metalloproteinases (MMPs) and loss of
collagen. Rubus idaeus L. (RI), also called red raspberry, is an important cash
crop that contains abundant antioxidant compounds. Sanguiin H-6 and lambertianin
C are the major ingredients presented in the extracts. Here, we studied the
protective effect of RI on UVB-induced photoaging in normal human dermal
fibroblasts (NHDFs). We found that RI notably reduced UVB-induced MMPs secretion
and pro-inflammatory mediators production, and significantly suppressed UVB
induced activation of mitogen-activated protein kinase (MAPK), nuclear factor
kappabeta, as well as activator protein 1. Additionally, treatment of NHDFs with
the ERK inhibitor (PD98059) and JNK inhibitor (SP600125) resulted in the
reduction of UVB-induced MMP-1 and IL-6 expressions, which demonstrated that the
inhibition of MMP-1 and IL-6 by RI is associated with the MAPK pathway.
Furthermore, we also found that RI accelerated procollagen type I synthesis by
activating the transforming growth factor-beta/Smad pathway and enhanced the
expression of cytoprotective antioxidants such as heme oxygenase-1 and NHD(P)H
quinone oxidoreductase 1 by promoting nuclear factor E2-related factor 2 nuclear
transfer. Overall, these findings demonstrated that RI was potentially effective
in preventing UVB induced skin photoaging.
PMID- 29966992
TI - Adding acceptance and commitment therapy to exposure and response prevention for
obsessive-compulsive disorder: A randomized controlled trial.
AB - The objective of this study was to test whether treatment acceptability, exposure
engagement, and completion rates could be increased by integrating acceptance and
commitment therapy (ACT) with traditional exposure and response prevention (ERP).
58 adults (68% female) diagnosed with obsessive-compulsive disorder (OCD; M age =
27, 80% white) engaged in a multisite randomized controlled trial of 16
individual twice-weekly sessions of either ERP or ACT + ERP. Assessors unaware of
treatment condition administered assessments of OCD, depression, psychological
flexibility, and obsessional beliefs at pretreatment, posttreatment, and six
month follow-up. Treatment acceptability, credibility/expectancy, and exposure
engagement were also assessed. Exposure engagement was high in both conditions
and there were no significant differences in exposure engagement, treatment
acceptability, or dropout rates between ACT + ERP and ERP. OCD symptoms,
depression, psychological inflexibility, and obsessional beliefs decreased
significantly at posttreatment and were maintained at follow-up in both
conditions. No between-group differences in outcome were observed using intent to
treat and predicted data from multilevel modeling. ACT + ERP and ERP were both
highly effective treatments for OCD, and no differences were found in outcomes,
processes of change, acceptability, or exposure engagement.
PMID- 29966993
TI - Temporal context cues in human fear conditioning: Unreinforced conditional
stimuli can segment learning into distinct temporal contexts and drive fear
responding.
AB - In associative learning, if stimulus A is presented in the same temporal context
as the conditional stimulus (CS) - outcome association (but not in a way that
allows an A-CS association to form) it becomes a temporal context cue, acquiring
the ability to activate this context and retrieve the CS-outcome association. We
examined whether a CS- presented during acquisition or extinction that predicted
the absence of the unconditional stimulus (US) could act as a temporal context
cue, reducing or enhancing responding, in differential fear conditioning. Two
groups received acquisition (CSx-US, CSa-noUS) in phase 1 and extinction (CSx
noUS; CSe-noUS) in phase 2 (AE groups), and two groups received extinction in
phase 1 and acquisition in phase 2 (EA groups). After a delay, participants were
presented with either CSa (AEa and EAa groups) or CSe (AEe and EAe groups).
Responding to CSx was enhanced after presentation of CSa but reduced after
presentation of CSe, suggesting that training was segmented into two learning
episodes and that the unreinforced CS present during an episode retrieved the CSx
US or CSx-noUS association. These findings suggest that temporal context cues may
enhance or reduce fear responding, providing an exciting new avenue for relapse
prevention research.
PMID- 29966994
TI - Investigation of the Prevalence of Pediculus humanus capitis and Risk Factors in
a Village in Isparta.
AB - OBJECTIVE: The aim of this study was to investigate the prevalence of Pediculus
humanus (P.h.) capitis infestation in school children in Sucullu Village,
Isparta. METHODS: The study was conducted from April to May 2016 in Sucullu
Village. Hair of 204 students were examined for eggs, nymphs, and adults of P.h.
capitis. Data regarding age, sex, family's type of living were recorded for each
child. RESULTS: It was found that 9.3%of students were infested by P.h capitis.
The prevalence of infestation was significantly higher in girls (17.4%) than in
boys (p<0.05). School children in the age group of 8-9 years exhibited higher
prevalence rates. Infestation rate was also high in livestock families (p<0.05).
CONCLUSION: This study revealed that socioeconomic status is a major factor that
influences the occurence of pediculosis among students of both sexes in Isparta.
Infestation is more common in crowded families.
PMID- 29966995
TI - Parasitic Twin Presenting Rudimentary Upper Limbs Causes a Unique Spectrum of
Anomalies of Autosite
PMID- 29966996
TI - Treatment of Graf Type IIa Hip Dysplasia: A Cut-off Value for Decision Making
AB - Background: The rate of spontaneous normalization in type IIa hips is reported to
be high, whereas dysplsia persists or worsens in 5%-10% of cases. Aims: To
evaluate the natural course of type IIa hips using Graf's own perspective of
physiological immaturity and maturational deficit. Study Design: A single center,
retrospective cohort study. Methods: This was an institutional review board
approved retrospective review of all patients diagnosed with type IIa hip
dysplasia at a single institution from 2012 to 2014. All patients included in the
study had hip ultrasonography at about 6 weeks and 3 months of age. To assess
reliability in alpha and beta angles, ultrasonography measurements were carried
out on the same image individually by all observers. The alpha and beta angles
were used as the main outcome measurements to evaluate hip maturation at the last
follow-up. A receiver operating characteristics curve was drawn at the 3 month
ultrasonography to evaluate the cut-off values for alpha and beta angles for
persistent dysplasia. Results: Sixty-four patients and 88 affected hips (63%
unilateral and 37% bilateral) were included. The mean age at diagnosis was 6.4+/
2.7 weeks. Fifty-four hips were type IIa(+) (physiologically immature) and 34
hips were type IIa(-) (maturational deficit) at the initial ultrasonography
evaluation. Improvement to type I was seen in 52 type IIa(+) and 17 type IIa(-)
hips. Receiver operating characteristic analyses showed that patients do well if
the alpha angle was >55 degrees (area under the curve: 0.86; p<0.001 for the
left hip and area under the curve: 0.72; p=0.008 for the right hip). Conclusion:
The cut-off alpha angle value of 55 degrees on initial ultrasonography should be
considered to prevent future dysplasia. An alpha angle <55 degrees on the
initial ultrasonography was an independent predictor of worsening sonographic
findings.
PMID- 29966997
TI - Vincristine as an Adjunct to Therapeutic Plasma Exchange for Thrombotic
Thrombocytopenic Purpura: A Single-Institution Experience
AB - Background: Thrombotic thrombocytopenic purpura is a potentially life-threatening
condition. Although the introduction of therapeutic plasma exchange has reduced
mortality rates from over 90% to 10%-20%, approximately 40% of patients relapse,
and outcomes may be fatal in refractory patients. There is clearly a need for
additional therapeutic approaches. Aims: To describe the outcomes of
relapsed/refractory thrombotic thrombocytopenic purpura patients treated with
vincristine as an adjunct to therapeutic plasma exchange. Study Design: Cross
sectional study. Methods: The medical records of all relapsed/refractory patients
with thrombotic thrombocytopenic purpura treated with vincristine adjunct to
therapeutic plasma exchange between October 2000 and December 2016 were
retrospectively reviewed. Diagnosis of thrombotic thrombocytopenic purpura was
based on clinical history, physical examination, and laboratory examinations.
Patient demographics, laboratory findings, initial date and duration of
therapeutic plasma exchange, dosage and time of administration of vincristine,
and outcomes were recorded. Results: The study included 15 patients [median age:
37 years (range: 26-65); 7 women and 8 men] with either relapsed or refractory
thrombotic thrombocytopenic purpura who were treated with vincristine as an
adjunct to therapeutic plasma exchange for a total of 22 episodes. Eighty-seven
percent of patients achieved remissions in 20 of 22 episodes, with a median
duration of remission of 29.5 months (range: 3-105). After a median follow-up of
55 months, 11 patients were alive. Vincristine was well tolerated with no safety
concerns. Conclusion: Vincristine offers a reasonable option for the treatment of
patients with relapsed/refractory thrombotic thrombocytopenic purpura. Further
studies evaluating vincristine in the front-line setting and in the
relapsed/refractory setting are needed to validate the role of vincristine in
thrombotic thrombocytopenic purpura patients.
PMID- 29966998
TI - An intrahepatic Portal Vein Aneurysm Presenting with Esophageal Variceal Bleeding
in a Pediatric Patient: A Rare Clinical Entity
PMID- 29966999
TI - Can NT-pro BNP Levels Predict Prognosis of Patients with Acute Exacerbations of
Chronic Obstructive Pulmonary Disease in the Intensive Care Unit?
AB - Background: The prognostic value of amino terminal pro-brain natriuretic peptide
levels in patients with acute exacerbation of chronic obstructive pulmonary
disease has not been fully established. Aims: To investigate the predictive value
of amino terminal pro-brain natriuretic peptide levels in terms of mortality,
need for noninvasive mechanical ventilation, invasive mechanical ventilation, and
weaning success. Study Design: Cohort study. Methods: Patients who were admitted
to intensive care unit between December 2015 and December 2016 due to acute
exacerbation of chronic obstructive pulmonary disease were included in the study.
Demographic data, noninvasive mechanical ventilation application, need for
invasive mechanical ventilation, amino terminal pro-brain natriuretic peptide
level, duration of mechanical ventilation, intensive care unit and hospital stay,
weaning success, and mortality rates were recorded. Results: A total of 110
patients (75 males) were included in the study. The mean age of the participants
was 69 (61-76) years, and the mean Acute Physiology and Chronic Health Evaluation
II score was 19 (15-23). The mean amino terminal pro-brain natriuretic peptide
level was found to be lower in cases with noninvasive mechanical ventilation
success than those with noninvasive mechanical ventilation failure (p=0.053). In
addition, the mean amino terminal pro-brain natriuretic peptide level was
significantly higher (4740 pg/mL vs. 3004 pg/mL, p=0.001) in patients who needed
invasive mechanical ventilation support than in patients who did not. The
mortality rate was significantly higher in patients who had an increasing trend
of amino terminal pro-brain natriuretic peptide levels during hospitalization
than in patients who had decreasing levels (59% vs. 23%, p=0.015). Based on the
receiver operating characteristic analysis, the increasing trend of amino
terminal pro-brain natriuretic peptide levels during intensive care unit stay
predicted mortality with area under curve of 0.84 (p<0.0001, 95% CI: 0.75-0.93)
and predicted invasive mechanical ventilation need with area under curve of 0.68.
Conclusion: In cases of acute exacerbation of chronic obstructive pulmonary
disease requiring mechanical ventilation, amino terminal pro-brain natriuretic
peptide measurement and monitoring of its trend may be a valuable asset in
predicting mortality, noninvasive mechanical ventilation, weaning success, and
need for invasive mechanical ventilation.
PMID- 29967000
TI - Methodological Shortcomings of Wrist-Worn Heart Rate Monitors Validations.
AB - Wearable sensor technology could have an important role for clinical research and
in delivering health care. Accordingly, such technology should undergo rigorous
evaluation prior to market launch, and its performance should be supported by
evidence-based marketing claims. Many studies have been published attempting to
validate wrist-worn photoplethysmography (PPG)-based heart rate monitoring
devices, but their contrasting results question the utility of this technology.
The reason why many validations did not provide conclusive evidence of the
validity of wrist-worn PPG-based heart rate monitoring devices is mostly
methodological. The validation strategy should consider the nature of data
provided by both the investigational and reference devices. There should be
uniformity in the statistical approach to the analyses employed in these
validation studies. The investigators should test the technology in the
population of interest and in a setting appropriate for intended use. Device
industries and the scientific community require robust standards for the
validation of new wearable sensor technology.
PMID- 29967001
TI - Transcriptomic Characterization of Endometrioid, Clear Cell, and High-Grade
Serous Epithelial Ovarian Carcinoma.
AB - Background: Endometrioid carcinoma (EC) and clear cell carcinoma (CC) histotypes
of epithelial ovarian cancer are understudied compared with the more common high
grade serous carcinomas (HGSC). We therefore sought to characterize EC and CC
transcriptomes in relation to HGSC.Methods: Following bioinformatics processing
and gene abundance normalization, differential expression analysis of RNA
sequence data collected on fresh-frozen tumors was completed with nonparametric
statistical analysis methods (55 ECs, 19 CCs, 112 HGSCs). Association of gene
expression with progression-free survival (PFS) was completed with Cox
proportional hazards models. Eight additional multi-histotype expression array
datasets (N = 852 patients) were used for replication.Results: In the discovery
set, tumors generally clustered together by histotype. Thirty-two protein-coding
genes were differentially expressed across histotype (P < 1 * 10-10) and showed
similar associations in replication datasets, including MAP2K6, KIAA1324, CDH1,
ENTPD5, LAMB1, and DRAM1 Nine genes associated with PFS (P < 0.0001) showed
similar associations in replication datasets. In particular, we observed shorter
PFS time for CC and EC patients with high gene expression for CCNB2, CORO2A,
CSNK1G1, FRMD8, LIN54, LINC00664, PDK1, and PEX6, whereas, the converse was
observed for HGSC patients.Conclusions: The results suggest important histotype
differences that may aid in the development of treatment options, particularly
those for patients with EC or CC.Impact: We present replicated findings on
transcriptomic differences and how they relate to clinical outcome for two of the
rarer ovarian cancer histotypes of EC and CC, along with comparison with the
common histotype of HGSC. Cancer Epidemiol Biomarkers Prev; 27(9); 1101-9.
(c)2018 AACR.
PMID- 29967003
TI - Understanding abdominal aortic aneurysm epidemiology: socioeconomic position
affects outcome.
AB - BACKGROUND: Low socioeconomic position (SEP) has been demonstrated to negatively
influence outcome in several cardiovascular patient groups. The aim of this study
was to analyse time trends of incidence of intact abdominal aortic aneurysm
(iAAA) and ruptured AAA (rAAA), respectively, and to investigate whether SEP had
any influence on the probability to present with rupture and, finally, to
determine the impact of SEP on outcome. METHODS: Nationwide population-based
study including all individuals with iAAA or rAAA in Sweden during 2001-2015.
RESULTS: The number of individuals with an AAA was 41 222; the majority were
identified as iAAA 33 254 (80.7%) and 7968 (19.3%) as rAAA. Time trends showed
decreasing incidence of rAAA but increase in iAAA during the study period.
Individuals with low income or low educational level were more likely to present
with a rAAA rather than iAAA: OR 2.16 (95 % CI 1.98 to 2.36, p<0.001) and OR 1.33
(95 % CI 1.21 to 1.46, p<0.001), respectively. Low income was also associated
with increased 90-day mortality and 1-year mortality after treatment for rAAA, OR
1.42 (95% CI 1.07 to 1.89, p=0.014) and OR 1.39 (95% CI 1.13 to 1.97, p=0.005).
CONCLUSION: This large nationwide study showed a decreasing incidence of rAAA.
Individuals with low SEP were found to have an augmented risk of presenting with
rAAA rather than iAAA and, in addition, to fare worse after repair. Consequently,
SEP should be regarded as a relevant risk factor that should be included in
considerations for improved care flow of patients with AAA.
PMID- 29967002
TI - Humanized Mouse Model to Study Type 1 Diabetes.
AB - Key requirements in type 1 diabetes (T1D) are in setting up new assays as
diagnostic biomarkers that will apply to prediabetes, likely T-cell assays, and
in designing antigen-specific therapies to prevent T1D development. New
preclinical models of T1D will be required to help with advancing both aims. By
crossing mouse strains that lack either murine MHC class I and class II genes and
insulin genes, we developed YES mice that instead express human HLA-A*02:01, HLA
DQ8, and insulin genes as transgenes. The metabolic and immune phenotype of YES
mice is basically identical to that of the parental strains. YES mice remain
insulitis and diabetes free up to 1 year of follow-up, maintain normoglycemia to
an intraperitoneal glucose challenge in the long-term range, have a normal beta
cell mass, and show normal immune responses to conventional antigens. This new
model has been designed to evaluate adaptive immune responses to human insulin on
a genetic background that recapitulates a human high-susceptibility HLA-DQ8
genetic background. Although insulitis free, YES mice develop T1D when challenged
with polyinosinic-polycytidylic acid. They allow the characterization of
preproinsulin epitopes recognized by CD8+ and CD4+ T cells upon immunization
against human preproinsulin or during diabetes development.
PMID- 29967004
TI - Validity of predictive equations for resting metabolic rate in healthy humans.
AB - Background: There are several predictive equations for estimating resting
metabolic rate (RMR) in healthy humans. Concordance of these equations against
measured RMR is variable, and often dependent on the extent of RMR. Part of the
discrepancy may be due to an insufficient accuracy of metabolic carts, but this
accuracy can be improved via a correction procedure. Objective: To determine the
validity of predictive RMR equations by comparing them against measured and
corrected (i.e. the reference) RMR. Methods: RMR was measured, in 69 healthy
volunteers (29 males/40 females; 32+/-8 years old; BMI 25.5+/-3.8 kg/m2) and then
corrected by simulating gas exchange through pure gases and high-precision mass
flow regulators. RMR was predicted using 13 published equations. Bland-Altman
analyses compared predicted vs. reference RMRs. Results: All equations correlated
well with the reference RMR (r>0.67; P<0.0001), but on average, over-predicted
the reference RMR (89-312 kcal/d; P<0.05). Based on Bland-Altman analyses, 12
equations showed a constant bias across RMR, but the bias was not different from
zero for nine of them. Three equations stood out because the absolute difference
between predicted and reference RMR was equal or lower than 200 kcal/d for >60%
of individuals (the Mifflin, Oxford and Muller equations). From them, only the
Oxford equations performed better in both males and females separately.
Conclusion: The Oxford equations are a valid alternative to predict RMR in
healthy adult humans. Gas-exchange correction appears to be a good practice for
the reliable assessment of RMR.
PMID- 29967005
TI - Behavioral Evidence and Neural Correlates of Perceptual Grouping by Motion in the
Barn Owl.
AB - Perceiving an object as salient from its surround often requires a preceding
process of grouping the object and background elements as perceptual wholes. In
humans, motion homogeneity provides a strong cue for grouping, yet it is unknown
to what extent this occurs in nonprimate species. To explore this question, we
studied the effects of visual motion homogeneity in barn owls of both genders, at
the behavioral as well as the neural level. Our data show that the coherency of
the background motion modulates the perceived saliency of the target object. An
object moving in an odd direction relative to other objects attracted more
attention when the other objects moved homogeneously compared with when moved in
a variety of directions. A possible neural correlate of this effect may arise in
the population activity of the intermediate/deep layers of the optic tectum. In
these layers, the neural responses to a moving element in the receptive field
were suppressed when additional elements moved in the surround. However, when the
surrounding elements all moved in one direction (homogeneously moving), they
induced less suppression of the response compared with nonhomogeneously moving
elements. Moreover, neural responses were more sensitive to the homogeneity of
the background motion than to motion-direction contrasts between the receptive
field and the surround. The findings suggest similar principles of saliency-by
motion in an avian species as in humans and show a locus in the optic tectum
where the underlying neural circuitry may exist.SIGNIFICANCE STATEMENT A critical
task of the visual system is to arrange incoming visual information to a
meaningful scene of objects and background. In humans, elements that move
homogeneously are grouped perceptually to form a categorical whole object. We
discovered a similar principle in the barn owl's visual system, whereby the
homogeneity of the motion of elements in the scene allows perceptually
distinguishing an object from its surround. The novel findings of these visual
effects in an avian species, which lacks neocortical structure, suggest that our
basic visual perception shares more universal principles across species than
presently thought, and shed light on possible brain mechanisms for perceptual
grouping.
PMID- 29967006
TI - Stimulation of the Prefrontal Cortex Reduces Intentions to Commit Aggression: A
Randomized, Double-Blind, Placebo-Controlled, Stratified, Parallel-Group Trial.
AB - Although prefrontal brain impairments are one of the best-replicated brain
imaging findings in relation to aggression, little is known about the causal role
of this brain region. This study tests whether stimulating the dorsolateral
prefrontal cortex using transcranial direct current stimulation (tDCS) reduces
the likelihood of engaging in aggressive acts, and the mechanism underlying this
relationship. In a double-blind, stratified, placebo-controlled, parallel-group,
randomized trial, 81 human adults (36 males, 45 females) were randomly assigned
to an active (N = 39) or placebo (N = 42) condition, and then followed up 1 d
after the experiment session. Intentions to commit aggressive acts and behavioral
aggression were assessed using hypothetical vignettes and a behavioral task,
respectively. The secondary outcome was the perception of the moral wrongfulness
of the aggressive acts. Compared with the sham controls, participants who
received anodal stimulation reported being less likely to commit physical and
sexual assault (p < 0.01). They also judged aggressive acts as more morally wrong
(p < 0.05). Perceptions of greater moral wrongfulness regarding the aggressive
acts accounted for 31% of the total effect of tDCS on intentions to commit
aggression. Results provide experimental evidence that increasing activity in the
prefrontal cortex can reduce intentions to commit aggression and enhance
perceptions of the moral wrongfulness of the aggressive acts. Findings shed light
on the biological underpinnings of aggression and theoretically have the
potential to inform future interventions for aggression and violence.SIGNIFICANCE
STATEMENT Aggressive behaviors pose significant public health risks.
Understanding the etiology of aggression is paramount to violence reduction.
Investigations of the neural basis of aggression have largely supported
correlational, rather than causal, interpretations, and the mediating processes
underlying the prefrontal-aggression relationship remain to be well elucidated.
Through a double-blind, stratified, placebo-controlled, parallel-group,
randomized trial, this study tested whether upregulation of the prefrontal cortex
reduces the likelihood of engaging in aggression. Results provide experimental
evidence that increasing prefrontal cortical activity can reduce intent to commit
aggressive acts. They also shed light on moral judgment as one mechanism that may
link prefrontal deficits to aggression and, in theory, have the potential to
inform future approaches toward reducing aggression.
PMID- 29967007
TI - Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body
Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early
Intervention.
AB - Humans possess three genetic isoforms of apolipoprotein E (ApoE)-ApoE2, ApoE3,
and ApoE4-that confer differential risk for Alzheimer's disease (AD); however,
the underlying mechanisms are poorly understood. This study sought to investigate
the impact of human ApoE isoforms on brain energy metabolism, an area
significantly perturbed in preclinical AD. A TaqMan custom array was performed to
examine the expression of a total of 43 genes involved in glucose and ketone body
transport and metabolism, focusing on pathways leading to the generation of
acetyl-CoA, in human ApoE gene-targeted replacement female mice. Consistent with
our previous findings, brains expressing ApoE2 exhibited the most robust profile,
whereas brains expressing ApoE4 displayed the most deficient profile on the
uptake and metabolism of glucose, the primary fuel for the brain. Specifically,
the three ApoE brains differed significantly in facilitated glucose transporters,
which mediate the entry of glucose into neurons, and hexokinases, which act as
the "gateway enzyme" in glucose metabolism. Interestingly, on the uptake and
metabolism of ketone bodies, the secondary energy source for the brain, ApoE2 and
ApoE4 brains showed a similar level of robustness, whereas ApoE3 brains presented
a relatively deficient profile. Further, ingenuity pathway analysis indicated
that the PPAR-gamma/PGC-1alpha signaling pathway could be activated in the ApoE2
brain and inhibited in the ApoE4 brain. Notably, PGC-1alpha overexpression
ameliorated ApoE4-induced deficits in glycolysis and mitochondrial respiration.
Overall, our data provide additional evidence that human ApoE isoforms
differentially modulate brain bioenergetic metabolism, which could serve as a
potential mechanism contributing to their discrete risk impact in AD.SIGNIFICANCE
STATEMENT We uncovered hexokinase as a key cytosolic point in the glucose
metabolism that is differentially modulated by the three ApoE genotypes. The
differences in hexokinase expression and activity exhibited in the three ApoE
brains may underlie their distinct impact on brain glucose utilization and
further susceptibility to AD. Therefore, a therapeutic approach that could
circumvent the deficiencies in the cytosolic metabolism of glucose by providing
glucose metabolizing intermediates, e.g., pyruvate, may hold benefits for ApoE4
carriers, who are at high risk for AD. The bioenergetic robustness may translate
into enhanced synaptic activity and, ultimately, reduces the risk of developing
AD and/or delays the onset of clinical manifestation.
PMID- 29967009
TI - Overview of the Cytoskeleton from an Evolutionary Perspective.
AB - SUMMARYOrganisms in the three domains of life depend on protein polymers to form
a cytoskeleton that helps to establish their shapes, maintain their mechanical
integrity, divide, and, in many cases, move. Eukaryotes have the most complex
cytoskeletons, comprising three cytoskeletal polymers-actin filaments,
intermediate filaments, and microtubules-acted on by three families of motor
proteins (myosin, kinesin, and dynein). Prokaryotes have polymers of proteins
homologous to actin and tubulin but no motors, and a few bacteria have a protein
related to intermediate filament proteins.
PMID- 29967008
TI - Aspirin Induces Lysosomal Biogenesis and Attenuates Amyloid Plaque Pathology in a
Mouse Model of Alzheimer's Disease via PPARalpha.
AB - Lysosomes play a central role in cellular homeostasis by regulating the cellular
degradative machinery. Because aberrant lysosomal function has been associated
with multiple lysosomal storage and neurodegenerative disorders, enhancement of
lysosomal clearance has emerged as an attractive therapeutic strategy.
Transcription factor EB (TFEB) is known as a master regulator of lysosomal
biogenesis and, here, we reveal that aspirin, one of the most widely used
medications in the world, upregulates TFEB and increases lysosomal biogenesis in
brain cells. Interestingly, aspirin induced the activation of peroxisome
proliferator-activated receptor alpha (PPARalpha) and stimulated the
transcription of Tfeb via PPARalpha. Finally, oral administration of low-dose
aspirin decreased amyloid plaque pathology in both male and female 5X familial
Alzheimer's disease (5XFAD) mice in a PPARalpha-dependent fashion. This study
reveals a new function of aspirin in stimulating lysosomal biogenesis via
PPARalpha and suggests that low-dose aspirin may be used in lowering storage
materials in Alzheimer's disease and lysosomal storage disorders.SIGNIFICANCE
STATEMENT Developing drugs for the reduction of amyloid beta containing senile
plaques, one of the pathological hallmarks of Alzheimer's disease (AD), is an
important area of research. Aspirin, one of the most widely used medications in
the world, activates peroxisome proliferator-activated receptor alpha (PPARalpha)
to upregulate transcription factor EB and increase lysosomal biogenesis in brain
cells. Accordingly, low-dose aspirin decreases cerebral plaque load in a mouse
model of Alzheimer's disease via PPARalpha. These results reveal a new mode of
action of aspirin that may be beneficial for AD and lysosomal storage disorders.
PMID- 29967010
TI - Detecting RNA G-Quadruplexes (rG4s) in the Transcriptome.
AB - RNA G-quadruplex (rG4) secondary structures are proposed to play key roles in
fundamental biological processes that include the modulation of transcriptional,
co-transcriptional, and posttranscriptional events. Recent methodological
developments that include predictive algorithms and structure-based sequencing
have enabled the detection and mapping of rG4 structures on a transcriptome-wide
scale at high sensitivity and resolution. The data generated by these studies
provide valuable insights into the potentially diverse roles of rG4s in biology
and open up a number of mechanistic hypotheses. Herein we highlight these
methodologies and discuss the associated findings in relation to rG4-related
biological mechanisms.
PMID- 29967011
TI - A Career in Patent Law: At the Cutting Edge of Science, but Not at the Bench.
AB - Patent law is an area that many people move into after obtaining a PhD in
biomedical science. Close to the cutting edge of research, patent agents draft
detailed descriptions of new biotechnology inventions required for patent
applications and engage with patent offices during the review process known as
patent prosecution. Jobs are also available as patent examiners who examine these
patent applications, and it is common for individuals to move between the two
jobs. A law firm is generally the best place to train as a patent agent, but
biotech companies and tech-transfer offices can provide an alternative route.
Although obtaining a law degree is not essential after your PhD, it is
recommended, and all patent agents must pass rigorous qualifying exams. Further
down the road, training in patent law offers opportunities for in-house work in
biotech companies, business development, and mergers and acquisitions.
PMID- 29967013
TI - Letter by Feng et al Regarding Article, "Lacunar Infarcts, but Not Perivascular
Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease".
PMID- 29967012
TI - Regulatory BC200 RNA in peripheral blood of patients with invasive breast cancer.
AB - Regulatory brain cytoplasmic 200 RNA (BC200 RNA) is highly expressed in human
mammary carcinoma cells. Here, we ask whether BC200 RNA becomes detectable in
peripheral blood of patients with invasive breast cancer. Using quantitative
reverse-transcription PCR (qRT-PCR) methodology, we observed that BC200 RNA blood
levels were significantly elevated, in comparison with healthy subjects, in
patients with invasive breast cancer prior to tumorectomy (p=0.001) and in
patients with metastatic breast cancer (p=0.003). In patients with invasive
breast cancer who had recently undergone tumorectomy, BC200 RNA blood levels were
not distinguishable from levels in healthy subjects. However, normality analysis
revealed a heterogeneous distribution of patients in this group, including a
subgroup of individuals with high residual BC200 RNA blood levels. In blood from
patients with invasive breast cancer, BC200 RNA was specifically detected in the
mononuclear leukocyte fraction. The qRT-PCR approach is sensitive enough to
detect as few as three BC200 RNA-expressing tumor cells. Our work establishes the
potential of BC200 RNA detection in blood to serve as a molecular indicator of
invasive breast malignancy.
PMID- 29967014
TI - High Neutrophil-to-Lymphocyte Ratio Predicts Stroke-Associated Pneumonia.
AB - Background and Purpose- Although there are a variety of risk factors and
predictive models for stroke-associated pneumonia (SAP), more objective and
easily accessible markers are still needed. In this study, we evaluated the
relationship between the neutrophil-to-lymphocyte ratio (NLR) and SAP in patients
with acute ischemic stroke. Methods- We assessed 1317 consecutive patients with
acute ischemic stroke. SAP was defined according to the modified Centers for
Disease Control and Prevention criteria. The severity of pneumonia was rated
using scores from the Pneumonia Severity Index, the quick Sequential Organ
Failure Assessment, and the Acute Physiology and Chronic Health Evaluation II.
The NLR was calculated after dividing absolute neutrophil counts by absolute
lymphocyte counts. Results- Among the total patients, SAP occurred in 112 (9.0%)
patients. Using a multivariable analysis, the NLR (adjusted odds ratio=1.55; 95%
confidence interval, 1.15-2.11; P=0.005) remained significant after adjusting for
confounders. In addition, age, atrial fibrillation, previous stroke history,
initial National Institutes of Health Stroke Scale score, and high-sensitivity C
reactive protein were also significant, independent of NLR. The NLR was higher in
the severe pneumonia group when it was assessed by Pneumonia Severity Index (
P<0.001), quick Sequential Organ Failure Assessment ( P<0.001), and Acute
Physiology and Chronic Health Evaluation II scores ( P=0.004). Furthermore,
patients who had SAP had worse clinical outcomes both during hospitalization and
after discharge. Conclusions- We demonstrated that a higher NLR predicted SAP in
patients with acute ischemic stroke. The NLR may help to identify high-risk
patients in time and provide clues for further studies about preventive
antibiotic therapy.
PMID- 29967015
TI - Pembrolizumab OK'd for Cervical Cancer.
AB - The FDA approved the PD-1 inhibitor pembrolizumab as a second-line treatment for
patients with recurrent or metastatic cervical cancer who expressed PD-L1 with a
combined positive score of at least 1. The approval was based on results of a
phase II trial in which patients treated with the drug had an objective response
rate of 14.3%.
PMID- 29967016
TI - Predictors of Peripherally Inserted Central Catheter Occlusion in the Outpatient
Parenteral Antimicrobial Therapy Setting.
AB - In this retrospective study of 285 patients receiving outpatient parenteral
antibiotic therapy (OPAT), the duration of antibiotic, use of double-lumen
catheters, and receipt of penicillin G and cloxacillin appeared to increase the
risk of peripherally inserted central catheter (PICC) occlusion. Physicians
should consider these factors when prescribing long-term antibiotic therapy.
Further studies are needed to evaluate methods to reduce PICC occlusion,
particularly when double-lumen PICCs are necessary and when cloxacillin or
penicillin G are the preferred treatment.
PMID- 29967017
TI - Clinical Regimens of Favipiravir Inhibit Zika Virus Replication in the Hollow
Fiber Infection Model.
AB - Zika virus (ZIKV) infection is associated with serious, long-term neurological
manifestations. There are currently no approved therapies for the treatment or
prevention of ZIKV infection. Favipiravir (FAV) is a viral polymerase inhibitor
with broad-spectrum activity. Our prior studies used static FAV concentrations
and demonstrated promising activity. However, the anti-ZIKV activity of dynamic
FAV concentrations has never been evaluated in a human cell line. Here we
employed the hollow-fiber infection model (HFIM) to simulate the human
pharmacokinetic (PK) profiles associated with the clinically utilized FAV dosage
regimens against influenza and Ebola viruses and assessed the viral burden
profiles. Clinically achievable FAV concentrations inhibited ZIKV replication in
HUH-7 cells in a dose-dependent fashion (50% effective concentration = 236.5
MUM). The viral burden profiles under dynamic FAV concentrations were predicted
by use of a mechanism-based mathematical model (MBM) and subsequently
successfully validated in the HFIM. This validated, translational MBM can now be
used to predict the anti-ZIKV activity of other FAV dosage regimens in the
presence of between-patient variability in pharmacokinetics. This approach can be
extended to rationally optimize FAV combination dosage regimens which hold
promise to treat ZIKV infections in nonpregnant patients.
PMID- 29967018
TI - Characterization of a Novel SXT/R391 Integrative and Conjugative Element Carrying
cfr, blaCTX-M-65, fosA3, and aac(6')-Ib-cr in Proteus mirabilis.
AB - A novel 139,487-bp SXT/R391 integrative and conjugative element, ICEPmiChnBCP11,
was characterized in Proteus mirabilis of swine origin in China. ICEPmiChnBCP11
harbors 20 different antimicrobial resistance genes, including the clinically
important rRNA methyltransferase gene cfr, the extended-spectrum beta-lactamase
gene blaCTX-M-65, fosfomycin resistance gene fosA3, and fluoroquinolone
resistance gene aac(6')-Ib-cr An ISPpu12-mediated composite transposon containing
various resistance genes and 10 copies of IS26 is inserted in hot spot 4.
ICEPmiChnBCP11 was successfully transferred to Escherichia coli.
PMID- 29967019
TI - Superior Pyronaridine Single-Dose Pharmacodynamics Compared to Artesunate,
Chloroquine, and Amodiaquine in a Murine Malaria Luciferase Model.
AB - Many previous in vitro and in vivo preclinical malaria drug studies have relied
on low-parasite-number drug inhibition numerically compared to the untreated
controls. In contrast, human malaria drug studies measure the high-parasite
density killing near 100 million/ml. Here we compared the in vivo single-dose
pharmacodynamic properties of artesunate and the 4-aminoquinolines pyronaridine,
chloroquine, and amodiaquine in a Plasmodium berghei ANKA-green fluorescent
protein GFP-luciferase-based murine malaria blood-stage model. Pyronaridine
exhibited dose-dependent killing, achieving parasite reductions near 5 to 6 logs
at 48 h, with complete cure at 10 mg/kg of body weight compared to artesunate,
which exhibited a 48-h dose-dependent killing with a 2-log drop at the
noncurative 250-mg/kg dose. Chloroquine, which was noncurative, and amodiaquine,
which was partially curative, had nearly the same initial dose-independent
killing, with a lag phase of minimal parasite reduction at all doses between 6
and 24 h, followed by a 2.5-log reduction at 48 h. In experiments with drug
treated, washed infected blood transfer to naive mice, chloroquine and
amodiaquine showed fewer viable parasites at the 24-h transfer than at the 8-h
transfer, measured by a prolonged return to parasitemia, despite a similar
parasite log reduction at these time points, in contrast to the correlation of
the parasite log reduction to viable parasites with artesunate and pyronaridine.
Artesunate in combination with pyronaridine exhibited an initial parasite
reduction similar to that achieved with pyronaridine, while with chloroquine or
amodiaquine, the reduction was similar to that achieved with artesunate. Single
oral-dose pyronaridine was much more potent in vivo than artesunate, chloroquine,
and amodiaquine during the initial decline in parasites and cure.
PMID- 29967020
TI - Broad-Spectrum Adaptive Antibiotic Resistance Associated with Pseudomonas
aeruginosa Mucin-Dependent Surfing Motility.
AB - Surfing motility is a novel form of surface adaptation exhibited by the
nosocomial pathogen Pseudomonas aeruginosa in the presence of the glycoprotein
mucin, which is found in high abundance at mucosal surfaces, especially those of
the lungs of cystic fibrosis and bronchiectasis patients. Here, we investigated
the adaptive antibiotic resistance of P. aeruginosa under conditions in which
surfing occurs compared that in to cells undergoing swimming. P. aeruginosa
surfing cells were significantly more resistant to several classes of
antibiotics, including aminoglycosides, carbapenems, polymyxins, and
fluoroquinolones. This was confirmed by incorporation of antibiotics into growth
medium, which revealed a concentration-dependent inhibition of surfing motility
that occurred at concentrations much higher than those needed to inhibit
swimming. To investigate the basis of resistance, transcriptome sequencing (RNA
Seq) was performed and revealed that surfing influenced the expression of
numerous genes. Included among genes dysregulated under surfing conditions were
multiple genes from the Pseudomonas resistome; these genes are known to affect
antibiotic resistance when mutated. Screening transposon mutants in these surfing
dysregulated resistome genes revealed that several of these mutants exhibited
changes in susceptibility to one or more antibiotics under surfing conditions,
consistent with a contribution to the observed adaptive resistance. In
particular, several mutants in resistome genes, including armR, recG, atpB, clpS,
nuoB, and certain hypothetical genes, such as PA5130, PA3576, and PA4292, showed
contributions to broad-spectrum resistance under surfing conditions and could be
complemented by their respective cloned genes. Therefore, we propose that surfing
adaption led to extensive multidrug adaptive resistance as a result of the
collective dysregulation of diverse genes.
PMID- 29967021
TI - Rapid Antibiotic Combination Testing for Carbapenem-Resistant Gram-Negative
Bacteria within Six Hours Using ATP Bioluminescence.
AB - To guide the timely selection of antibiotic combinations against carbapenem
resistant Gram-negative bacteria (CR-GNB), an in vitro test with a short
turnaround time is essential. We developed an in vitro ATP bioluminescence assay
to determine effective antibiotic combinations against CR-GNB within 6 h. We
tested 42 clinical CR-GNB strains (14 Acinetobacter baumannii, 14 Pseudomonas
aeruginosa, and 14 Klebsiella pneumoniae strains) against 74 single antibiotics
and two-antibiotic combinations. Bacteria (approximately 5 log10 CFU/ml) were
incubated with an antibiotic(s) at 35 degrees C; ATP bioluminescence was measured
at 6 h and 24 h; and the measurements were compared to viable counts at 24 h.
Receiver operating characteristic (ROC) curves were used to determine the optimal
luminescence thresholds (TRLU) for distinguishing between inhibitory and
noninhibitory combinations. The areas under the 6-h and 24-h ROC curves were
compared using the DeLong method. Prospective validation of the established
thresholds was conducted using 18 additional CR-GNB. The predictive accuracy of
TRLU for the 6-h ATP bioluminescence assay was 77.5% when all species were
analyzed collectively. Predictive accuracies ranged from 73.7% to 82.7% when each
species was analyzed individually. Upon comparison of the areas under the 6-h and
24-h ROC curves, the 6-h assay performed significantly better than the 24-h assay
(P < 0.01). Predictive accuracy remained high upon prospective validation of the
6-h ATP assay (predictive accuracy, 79.8%; 95% confidence interval [CI], 77.6 to
81.9%), confirming the external validity of the assay. Our findings indicate that
our 6-h ATP bioluminescence assay can provide guidance for prospective selection
of antibiotic combinations against CR-GNB in a timely manner and may be useful in
the management of CR-GNB infections.
PMID- 29967022
TI - Pharmacodynamic Target Attainment for Cefepime, Meropenem, and Piperacillin
Tazobactam Using a Pharmacokinetic/Pharmacodynamic-Based Dosing Calculator in
Critically Ill Patients.
AB - This was a prospective study to determine if pharmacokinetic/pharmacodynamic
(PK/PD)-based antibiotic dosing software aids in achieving concentration targets
in critically ill patients receiving cefepime (n = 10), meropenem (n = 20), or
piperacillin-tazobactam (n = 19). Antibiotic calculator doses targeting a >90%
probability of target attainment (PTA) differed from package insert doses for
22.4% (11/49) of patients. Target attainment was achieved for 98% of patients
(48/49). A PK/PD-based antibiotic dosing calculator provides beta-lactam doses
with a high PTA in critically ill patients.
PMID- 29967023
TI - Spread of blaCTX-M-15-Producing Enterobacteriaceae and OXA-23-Producing
Acinetobacter baumannii Sequence Type 2 in Tunisian Seafood.
AB - Bivalves are filter-feeding animals and markers of bacterial pollution. We report
a massive spread of blaCTX-M-15 through dominant Escherichia coli and Klebsiella
pneumoniae lineages and/or plasmid subtypes (F31:A4:B1) as well as the presence
of OXA-23-producing Acinetobacter baumannii sequence type 2 (ST2) in seafood,
highlighting a direct risk for the consumer. These findings should urge
authorities to consider hospital effluents, and also farm and urban effluents, as
important sources of extended-spectrum-beta-lactamase (ESBL)/carbapenemase
producers that filter-feeding animals can concentrate and further spread to
humans.
PMID- 29967024
TI - Gold Nanoparticle-Conjugated Cinnamic Acid Exhibits Antiacanthamoebic and
Antibacterial Properties.
AB - trans-Cinnamic acid (CA) is a natural organic compound. Using amoebicidal assays,
for the first time we showed that CA affected the viability of the protist
pathogen Acanthamoeba castellanii Conjugation with gold nanoparticles (AuNPs)
enhanced the antiamoebic effects of CA. CA-coated AuNPs (CA-AuNPs) also exhibited
significant excystation and encystation activity, compared to CA and AuNPs alone.
Pretreatment of amoebae with CA-AuNPs inhibited A. castellanii-mediated host cell
cytotoxicity. Moreover, CA-AuNPs exhibited potent effects against methicillin
resistant Staphylococcus aureus and neuropathogenic Escherichia coli K1 and
protected host cells against bacteria-mediated host cell death.
PMID- 29967025
TI - Azithromycin in Combination with Ceftriaxone Reduces Systemic Inflammation and
Provides Survival Benefit in a Murine Model of Polymicrobial Sepsis.
AB - Sepsis is a life-threatening systemic inflammatory condition triggered as a
result of an excessive host immune response to infection. In the past,
immunomodulators have demonstrated a protective effect in sepsis. Azithromycin (a
macrolide antibiotic) has immunomodulatory activity and was therefore evaluated
in combination with ceftriaxone in a clinically relevant murine model of sepsis
induced by cecal ligation and puncture (CLP). First, mice underwent CLP and 3 h
later were administered the vehicle or a subprotective dose of ceftriaxone (100
mg/kg of body weight subcutaneously) alone or in combination with an
immunomodulatory dose of azithromycin (100 mg/kg intraperitoneally). Survival was
monitored for 5 days. In order to assess the immunomodulatory activity,
parameters such as plasma and lung cytokine (interleukin-6 [IL-6], IL-1beta,
tumor necrosis factor alpha) concentrations, the plasma glutathione (GSH)
concentration, plasma and lung myeloperoxidase (MPO) concentrations, body
temperature, blood glucose concentration, and total white blood cell count, along
with the bacterial load in blood, peritoneal lavage fluid, and lung homogenate,
were measured 18 h after CLP challenge. Azithromycin in the presence of
ceftriaxone significantly improved the survival of CLP-challenged mice. Further,
the combination attenuated the elevated levels of inflammatory cytokines and MPO
in plasma and lung tissue and increased the body temperature and blood glucose
and GSH concentrations, which were otherwise markedly decreased in CLP-challenged
mice. Ceftriaxone produced a significant reduction in the bacterial load, while
coadministration of azithromycin did not produce a further reduction. Therefore,
the survival benefit offered by azithromycin was due to immunomodulation and not
its antibacterial action. The findings of this study indicate that azithromycin,
in conjunction with appropriate antibacterial agents, could provide clinical
benefits in sepsis.
PMID- 29967026
TI - Prevalence and Genetic Analysis of mcr-3-Positive Aeromonas Species from Humans,
Retail Meat, and Environmental Water Samples.
AB - The mobile colistin resistance gene mcr-3 is globally disseminated in both
Enterobacteriaceae and Aeromonas species, with the latter potentially serving as
a reservoir for this gene. Here, we investigated the prevalence of mcr-3 in
rectal swabs from humans, in food-producing animals and their products, and in
the aquatic environment, and we investigated the genetic relationships between
the mcr-3-positive isolates. An enriched broth screening method was used to
detect mcr-3 in samples, and species identification of isolates from positive
samples was carried out by matrix-assisted laser desorption ionization-time of
flight mass spectrometry and shotgun sequencing. All mcr-3-positive isolates were
subjected to antimicrobial susceptibility testing, conjugation, and whole-genome
sequencing. Ten Aeromonas isolates, including 2 from human rectal swabs, 1 from
pork, 3 from chicken meat, and 4 from the aquatic environment, were positive for
mcr-3, but only 2 showed resistance to colistin. In addition to the mcr-3
variants identified previously (the novel variants were termed mcr-3.13 to mcr
3.18), all isolates harbored mcr-3-like genes downstream of the mcr-3 variants.
The MCR-3.13 to MCR-3.18 proteins exhibited only 89.2% to 96.1% amino acid
identity to the original MCR-3 protein. Whole-genome sequence analysis indicated
diversity within the genetic environments of mcr-3-positive Aeromonas isolates
and possible transmission between different sources in China and even worldwide.
Close relationships between mcr-3-positive and mcr-3-negative Aeromonas isolates
suggested that mcr-3 might be common in Aeromonas species, which are not inherent
hosts of mcr-3 but may act as an important reservoir of this mobile colistin
resistance gene.
PMID- 29967027
TI - Is It Time for Systematic Voriconazole Pharmacogenomic Investigation for Central
Nervous System Aspergillosis?
AB - Voriconazole is the standard treatment for invasive aspergillosis but requires
therapeutic drug monitoring to optimize therapy. We report two cases of central
nervous system aspergillosis treated with voriconazole. Because of low trough
plasma concentrations, we identified gain-of-function mutations in CYP2C19 that
were partially responsible for the therapeutic failure of voriconazole. We
suggest that systematic voriconazole pharmacogenomic investigation of cerebral
aspergillosis be performed to avoid effective therapy delay in this life
threatening disease.
PMID- 29967028
TI - Prevalence of Inappropriate Antibiotic Prescribing in Primary Care Clinics within
a Veterans Affairs Health Care System.
AB - Data are needed from outpatient settings to better inform antimicrobial
stewardship. In this study, a random sample of outpatient antibiotic
prescriptions by primary care providers (PCPs) at our health care system was
reviewed and compared to consensus guidelines. Over 12 months, 3,880 acute
antibiotic prescriptions were written by 76 PCPs caring for 40,734 patients
(median panel, 600 patients; range, 33 to 1,547). PCPs ordered a median of 84
antibiotic prescriptions per 1,000 patients per year. Azithromycin (25.8%),
amoxicillin-clavulanate (13.3%), doxycycline (12.4%), amoxicillin (11%),
fluoroquinolones (11%), and trimethoprim-sulfamethoxazole (10.6%) were prescribed
most commonly. Medical records corresponding to 300 prescriptions from 59 PCPs
were analyzed in depth. The most common indications for these prescriptions were
acute respiratory tract infection (28.3%), urinary tract infection (23%), skin
and soft tissue infection (15.7%), and chronic obstructive pulmonary disease
(COPD) exacerbation (6.3%). In 5.7% of cases, no reason for the prescription was
listed. No antibiotic was indicated in 49.7% of cases. In 12.3% of cases, an
antibiotic was indicated, but the prescribed agent was guideline discordant. In
another 14% of cases, a guideline-concordant antibiotic was given for a guideline
discordant duration. Therefore, 76% of reviewed prescriptions were inappropriate.
Ciprofloxacin and azithromycin were most likely to be prescribed inappropriately.
A non-face-to-face encounter prompted 34% of prescriptions. The condition for
which an antibiotic was prescribed was not listed in primary or secondary
diagnosis codes in 54.5% of clinic visits. In conclusion, there is an enormous
opportunity to reduce inappropriate outpatient antibiotic prescriptions.
PMID- 29967029
TI - A wobbly road to drug resistance in melanoma: tRNA-modifying enzymes in
translation reprogramming.
PMID- 29967031
TI - Digital consultations-overcoming cultural resistance to change.
PMID- 29967030
TI - RIM-binding proteins recruit BK-channels to presynaptic release sites adjacent to
voltage-gated Ca2+-channels.
AB - The active zone of presynaptic nerve terminals organizes the neurotransmitter
release machinery, thereby enabling fast Ca2+-triggered synaptic vesicle
exocytosis. BK-channels are Ca2+-activated large-conductance K+-channels that
require close proximity to Ca2+-channels for activation and control Ca2+
triggered neurotransmitter release by accelerating membrane repolarization during
action potential firing. How BK-channels are recruited to presynaptic Ca2+
channels, however, is unknown. Here, we show that RBPs (for RIM-binding
proteins), which are evolutionarily conserved active zone proteins containing SH3
and FN3-domains, directly bind to BK-channels. We find that RBPs interact with
RIMs and Ca2+-channels via their SH3-domains, but to BK-channels via their FN3
domains. Deletion of RBPs in calyx of Held synapses decreased and decelerated
presynaptic BK-currents and depleted BK-channels from active zones. Our data
suggest that RBPs recruit BK-channels into a RIM-based macromolecular active zone
complex that includes Ca2+-channels, synaptic vesicles, and the membrane fusion
machinery, thereby enabling tight spatio-temporal coupling of Ca2+-influx to Ca2+
triggered neurotransmitter release in a presynaptic terminal.
PMID- 29967032
TI - Lipid-dependence of target membrane stability during influenza viral fusion.
AB - Although influenza kills about a half million people each year, even after
excluding pandemics, there is only one set of antiviral drugs: neuraminidase
inhibitors. By using a new approach utilizing giant unilamellar vesicles and
infectious X-31 influenza virus, and testing for the newly identified pore
intermediate of membrane fusion, we observed ~30-87% poration, depending upon
lipid composition. Testing the hypothesis that spontaneous curvature (SC) of the
lipid monolayer controls membrane poration, our Poisson model and Boltzmann
energetic considerations suggest a transition from a leaky to a non-leaky fusion
pathway depending on the SC of the target membrane. When the target membrane SC
is below approximately -0.20 nm-1 fusion between influenza virus and target
membrane is predominantly non-leaky while above that fusion is predominantly
leaky, suggesting that influenza hemagglutinin (HA)-catalyzed topological
conversion of target membranes during fusion is associated with a loss of
membrane integrity.
PMID- 29967033
TI - Switch-like PKA responses in the nucleus of striatal neurons.
AB - Although it is known that protein kinase A (PKA) in the nucleus regulates gene
expression, the specificities of nuclear PKA signaling remain poorly understood.
Here, we combined computational modeling and live-cell imaging of PKA-dependent
phosphorylation in mouse brain slices to investigate how transient dopamine
signals are translated into nuclear PKA activity in cortical pyramidal neurons
and striatal medium spiny neurons. We observed that the nuclear PKA signal in
striatal neurons featured an ultrasensitive responsiveness, associated with fast
all-or-none responses, which is not consistent with the commonly accepted theory
of a slow and passive diffusion of catalytic PKA in the nucleus. Our numerical
model suggests that a positive feed-forward mechanism inhibiting nuclear
phosphatase activity - possibly mediated by DARPP-32 (also known as PPP1R1B) -
could be responsible for this non-linear pattern of nuclear PKA response,
allowing for a better detection of the transient dopamine signals that are often
associated with reward-mediated learning.
PMID- 29967034
TI - The ESCRT protein CHMP2B acts as a diffusion barrier on reconstituted membrane
necks.
AB - Endosomal sorting complexes required for transport (ESCRT)-III family proteins
catalyze membrane remodeling processes that stabilize and constrict membrane
structures. It has been proposed that stable ESCRT-III complexes containing
CHMP2B could establish diffusion barriers at the post-synaptic spine neck. In
order to better understand this process, we developed a novel method based on
fusion of giant unilamellar vesicles to reconstitute ESCRT-III proteins inside
GUVs, from which membrane nanotubes are pulled. The new assay ensures that ESCRT
III proteins polymerize only when they become exposed to physiologically relevant
membrane topology mimicking the complex geometry of post-synaptic spines. We
establish that CHMP2B, both full-length and with a C-terminal deletion (DeltaC),
preferentially binds to membranes containing phosphatidylinositol 4,5
bisphosphate [PI(4,5)P2]. Moreover, we show that CHMP2B preferentially
accumulates at the neck of membrane nanotubes, and provide evidence that CHMP2B
DeltaC prevents the diffusion of PI(4,5)P2 lipids and membrane-bound proteins
across the tube neck. This indicates that CHMP2B polymers formed at a membrane
neck may function as a diffusion barrier, highlighting a potential important
function of CHMP2B in maintaining synaptic spine structures.
PMID- 29967035
TI - Pharmacological Treatment of Arterial Hypertension in Children and Adolescents: A
Network Meta-Analysis.
AB - Pharmacological treatment is indicated in children and adolescents with
hypertension unresponsive to lifestyle modifications, but there is not enough
evidence to recommend 1 class of antihypertensive drugs over others. We performed
a network meta-analysis to compare the results of available randomized clinical
trials on pharmacological treatment of pediatric hypertension. From a total of
554 potentially relevant studies, 13 randomized placebo-controlled clinical
trials enrolling >=50 patients and a follow-up >=4 weeks were included. The
reduction of systolic blood pressure (SBP) and diastolic BP (DBP) after treatment
were the coprimary end points. A total of 2378 pediatric patients, with a median
age of 12 years, were included in the analysis. After a median follow-up of 35
days, lisinopril and enalapril were found to be superior to placebo in reducing
SBP and DBP, whereas only for DBP, losartan was found to be superior to placebo
and lisinopril and enalapril were found to be superior to eplerenone. Angiotensin
converting enzyme inhibitors and angiotensin receptor blockers were associated
with a greater SBP and DBP reduction compared with placebo, likewise the
mineralocorticoid receptor antagonist was inferior to angiotensin-converting
enzyme inhibitors in DBP reduction. The analysis was adjusted for study-level
mean age, percentage of women, mean baseline blood pressure, and mean weight,
only the latter significantly affected DBP reduction. According to the present
analysis, angiotensin-converting enzyme inhibitors and angiotensin receptor
blockers could represent the best choice as antihypertensive treatment for
pediatric hypertension. However, because of the paucity of available data for the
other classes of antihypertensive drugs, definitive conclusions are not allowed
and further randomized controlled trials are warranted.
PMID- 29967036
TI - Advanced and Accurate Mobile Health Tracking Devices Record New Cardiac Vital
Signs.
AB - Cardiovascular disease remains the leading cause of death and disease worldwide.
As demands on an already resource-constrained healthcare system intensify,
disease prevention in the future will likely depend on out-of-office monitoring
of cardiovascular risk factors. Mobile health tracking devices that can track
blood pressure and heart rate, in addition to new cardiac vital signs, such as
physical activity level and pulse wave velocity (PWV), offer a promising
solution. An initial barrier is the development of accurate and easily-scalable
platforms. In this study, we made a customized smartphone app and used mobile
health devices to track PWV, blood pressure, heart rate, physical activity, sleep
duration, and multiple lifestyle risk factors in ~250 adults for 17 continual
weeks. Eligible participants were identified by a company database and then were
consented and enrolled using only a smartphone app, without any special training
given. Study participants reported high overall satisfaction, and 73% of
participants were able to measure blood pressure and PWV, <1 hour apart, for at
least 14 of 17 weeks. The study population's blood pressure, PWV, heart rate,
activity levels, sleep duration, and the interrelationships among these
measurements were found to closely match either population averages or values
obtained from studies performed in a controlled setting. As a proof-of-concept,
we demonstrated the accuracy and ease, as well as many challenges, of using
mHealth technology to accurately track PWV and new cardiovascular vital signs at
home.
PMID- 29967037
TI - Self-Management of Postnatal Hypertension: The SNAP-HT Trial.
AB - : Hypertension affects 1 in 10 pregnancies, often persisting postpartum, when
antihypertensive requirements may vary substantially. This unmasked, randomized
controlled trial evaluated the feasibility and effects on blood pressure (BP) of
self-management of postpartum hypertension. Women with gestational hypertension
or preeclampsia, requiring postnatal antihypertensive treatment, were randomized
to self-management or usual care. Self-management entailed daily home BP
monitoring and automated medication reduction via telemonitoring. Women attended
5 follow-up visits during 6 months. The primary outcome was feasibility:
specifically recruitment, retention, and compliance with follow-up rates.
Secondary outcomes included BP control and safety, analyzed on an intention-to
treat basis. Forty-nine percent (91/186) of those women approached were
randomized (45 intervention, 46 control), and 90% (82/91) finished follow-up. The
groups had similar baseline characteristics. After randomization, BP was lower in
the intervention group, most markedly at 6 weeks: intervention group mean (SD),
systolic 121.6 (8.7)/diastolic 80.5 (6.6) mm Hg; control group, systolic 126.6
(11.0)/diastolic 86.0 (9.7) mm Hg; adjusted differences (95% confidence
interval), systolic -5.2 (-9.3 to -1.2)/diastolic -5.8 (-9.1 to -2.5) mm Hg.
Diastolic BP remained significantly lower in those self-managing to 6 months:
adjusted difference -4.5 (-8.1 to -0.8) mm Hg. This is the first randomized
evaluation of BP self-management postpartum and indicates it would be feasible to
trial this intervention in larger studies. Self-management resulted in better
diastolic BP control to 6 months, even beyond medication cessation. CLINICAL
TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
NCT02333240.
PMID- 29967038
TI - Genes for Preeclampsia: An Opportunity for Blood Pressure Genomics.
PMID- 29967040
TI - Association Between Prepregnancy Cardiovascular Function and Subsequent
Preeclampsia or Fetal Growth Restriction.
AB - Preeclampsia and fetal growth restriction during pregnancy are associated with
increased risk of maternal cardiovascular disease later in life. It is unclear
whether this association is causal or driven by similar antecedent risk factors.
Clarification requires recruitment before conception which is methodologically
difficult with high attrition rates and loss of outcome numbers to
nonconception/miscarriage. Few prospective studies have, therefore, been
adequately powered to address these questions. We recruited 530 healthy women
(mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac
index, stroke volume, total peripheral resistance, mean arterial pressure, and
heart rate before pregnancy. Participants were followed to completion of
subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously
conceived pregnancies, 15 (4.2%) were affected by preeclampsia and fetal growth
restriction. Women who subsequently developed preeclampsia/fetal growth
restriction had lower preconception cardiac output (4.9 versus 5.8 L/min;
P=0.002) and cardiac index (2.9 versus 3.3 L/min per meter2; P=0.031) while mean
arterial pressure (87.1 versus 82.3 mm Hg; P=0.05) and total peripheral
resistance (1396.4 versus 1156.1 dynes sec cm-5; P<0.001) were higher.
Longitudinal trajectories for cardiac output and total peripheral resistance were
similar between affected and healthy pregnancies, but the former group showed a
more exaggerated fall in mean arterial pressure in the first trimester, followed
by a steeper rise and a steeper fall to postpartum values. Significant
relationships were observed between cardiac output, total peripheral resistance,
and mean arterial pressure and gestational epoch. We conclude that in healthy
women, an altered prepregnancy hemodynamic phenotype is associated with the
subsequent development of preeclampsia/fetal growth restriction.
PMID- 29967041
TI - Does Intensive Glucose Control Cancel Out Benefits of Systolic Blood Pressure
Target <120 mm Hg in Patients With Diabetes Mellitus Participating in ACCORD?
PMID- 29967042
TI - Can Blood Pressure Self-Monitoring Improve Postpartum Management of Pregnancy
Associated Hypertension?
PMID- 29967039
TI - Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1.
AB - The genetic susceptibility to preeclampsia, a pregnancy-specific complication
with significant maternal and fetal morbidity, has been poorly characterized. To
identify maternal genes associated with preeclampsia risk, we assembled 498 cases
and 1864 controls of European ancestry from preeclampsia case-control collections
in 5 different US sites (with additional matched population controls), genotyped
samples on a cardiovascular gene-centric array composed of variants from ~2000
genes selected based on prior genetic studies of cardiovascular and metabolic
diseases and performed case-control genetic association analysis on 27 429
variants passing quality control. In silico replication testing of 9 lead signals
with P<10-4 was performed in independent European samples from the SOPHIA (Study
of Pregnancy Hypertension in Iowa) and Inova cohorts (212 cases, 456 controls).
Multiethnic assessment of lead signals was then performed in samples of black (26
cases, 136 controls), Hispanic (132 cases, 468 controls), and East Asian (9
cases, 80 controls) ancestry. Multiethnic meta-analysis (877 cases, 3004
controls) revealed a study-wide statistically significant association of the
rs9478812 variant in the pleiotropic PLEKHG1 gene (odds ratio, 1.40 [1.23-1.60];
Pmeta=5.90*10-7). The rs9478812 effect was even stronger in the subset of
European cases with known early-onset preeclampsia (236 cases diagnosed <37
weeks, 1864 controls; odds ratio, 1.59 [1.27-1.98]; P=4.01*10-5). PLEKHG1
variants have previously been implicated in genome-wide association studies of
blood pressure, body weight, and neurological disorders. Although larger studies
are required to further define maternal preeclampsia heritability, this study
identifies a novel maternal risk locus for further investigation.
PMID- 29967043
TI - Activity Tracking's Newest Companion: Pulse Wave Velocity.
PMID- 29967044
TI - Are the American Heart Association/American College of Cardiology High Blood
Pressure Guidelines Fit for Global Purpose?: Thoughts From the International
Society of Hypertension.
PMID- 29967046
TI - General practice: new technology isn't necessarily better.
PMID- 29967045
TI - Benefits of Intensive Blood Pressure Treatment in Patients With Type 2 Diabetes
Mellitus Receiving Standard but Not Intensive Glycemic Control.
AB - This study aimed to assess whether intensive blood pressure (BP) treatment has
benefits in preventing cardiovascular events, including heart failure in patients
with type 2 diabetes mellitus. Using the ACCORD BP trial (Action to Control
Cardiovascular Risk in Diabetes Blood Pressure) data, hazard ratios for
cardiovascular events with 95% confidence intervals were calculated using the Cox
proportional hazard models to compare the time to the first cardiovascular event
in patients receiving standard (n=2362) or intensive glycemic control (n=2371).
The overall mean follow-up period was 4.5 years, and cardiovascular events were
confirmed in 528 patients. The cardiovascular event risk in patients receiving
standard glycemic control was significantly lower in the intensive BP treatment
group than in the standard BP treatment group (hazard ratio, 0.71; 95% confidence
interval, 0.56-0.90; P=0.005), whereas that in patients receiving intensive
glycemic control did not differ significantly between the groups (hazard ratio,
1.06; 95% confidence interval, 0.83-1.36; P=0.61). There was a significant
interaction between the BP treatment strategy and glycemic control (P=0.02). The
stroke risk in patients receiving standard glycemic control was significantly
lower in the intensive BP treatment group, but not in patients receiving
intensive glycemic control. Although not significant, all-cause mortality in
patients receiving intensive glycemic control was higher in patients receiving
intensive BP treatment than in those receiving standard BP treatment (hazard
ratio, 1.38; 95% confidence interval, 0.99-1.92; P=0.05). Benefits of intensive
BP treatment were observed only in ACCORD BP participants receiving standard
glycemic control without additional risk factors.
PMID- 29967047
TI - HEAT INDUCIBLE LIPASE1 Remodels Chloroplastic Monogalactosyldiacylglycerol by
Liberating alpha-Linolenic Acid in Arabidopsis Leaves under Heat Stress.
AB - Under heat stress, polyunsaturated acyl groups, such as alpha-linolenate (18:3)
and hexadecatrienoate (16:3), are removed from chloroplastic glycerolipids in
various plant species. Here, we showed that a lipase designated HEAT INDUCIBLE
LIPASE1 (HIL1) induces the catabolism of monogalactosyldiacylglycerol (MGDG)
under heat stress in Arabidopsis thaliana leaves. Using thermotolerance tests, a
T-DNA insertion mutant with disrupted HIL1 was shown to have a heat stress
sensitive phenotype. Lipidomic analysis indicated that the decrease of 34:6-MGDG
under heat stress was partially impaired in the hil1 mutant. Concomitantly, the
heat-induced increment of 54:9-triacylglycerol in the hil1 mutant was 18% lower
than that in the wild-type plants. Recombinant HIL1 protein digested MGDG to
produce 18:3-free fatty acid (18:3-FFA), but not 18:0- and 16:0-FFAs. A transient
assay using fluorescent fusion proteins confirmed chloroplastic localization of
HIL1. Transcriptome coexpression network analysis using public databases
demonstrated that the HIL1 homolog expression levels in various terrestrial
plants are tightly associated with chloroplastic heat stress responses. Thus,
HIL1 encodes a chloroplastic MGDG lipase that releases 18:3-FFA in the first
committed step of 34:6 (18:3/16:3)-containing galactolipid turnover, suggesting
that HIL1 has an important role in the lipid remodeling process induced by heat
stress in plants.
PMID- 29967048
TI - Nuclear Positioning Requires a Tug-of-War between Kinesin Motors.
PMID- 29967052
TI - NHS proposes to stop funding 17 "unnecessary" procedures.
PMID- 29967051
TI - miR-876-3p regulates glucose homeostasis and insulin sensitivity by targeting
adiponectin.
AB - miRNA have been known to regulate diverse cellular and molecular functions. In
the earlier study, we have reported that adipocytes differentiated from human
mesenchymal stem cells (hMSC) on 72hr chronic insulin (CI) treatment exhibit
insulin resistance (IR). Present study has further explored above model to
investigate the role of early expressed miRNAs within human adipocytes to
modulate differential adipokine expression as observed during IR. Our results
highlight that miR-876-3p regulate glucose homeostasis and its dysregulation lead
to IR. We found that miR-876-3p level is a critical determinant of adiponectin
expression by virtue of its target within adiponectin 3'UTR. Regulatory effect of
miR-876-3p impacts crosstalk between adiponectin and insulin signaling.
Rosiglitazone treatment in CI induced IR adipocytes drastically reduced miR-876
3p expression and increased adiponectin level. In line with this, lentiviral
mediated inhibition of miR-876-3p expression ameliorated CI and high fat diet
(HFD) induced insulin resistance in adipocytes differentiated from hMSC and
C57BL/6 mice. Our findings thus suggest that modulating miR-876-3p expression
could provide novel opportunities for therapeutic intervention of obesity
associated metabolic syndrome.
PMID- 29967049
TI - Chloroplast Acetyltransferase NSI Is Required for State Transitions in
Arabidopsis thaliana.
AB - The amount of light energy received by the photosynthetic reaction centers
photosystem II (PSII) and photosystem I (PSI) is balanced through state
transitions. Reversible phosphorylation of a light-harvesting antenna trimer (L
LHCII) orchestrates the association between L-LHCII and the photosystems, thus
adjusting the amount of excitation energy received by the reaction centers. In
this study, we identified the enzyme NUCLEAR SHUTTLE INTERACTING (NSI; AT1G32070)
as an active lysine acetyltransferase in the chloroplasts of Arabidopsis thaliana
Intriguingly, nsi knockout mutant plants were defective in state transitions,
even though they had a similar LHCII phosphorylation pattern as the wild type.
Accordingly, nsi plants were not able to accumulate the PSI-LHCII state
transition complex, even though the LHCII docking site of PSI and the overall
amounts of photosynthetic protein complexes remained unchanged. Instead, the nsi
mutants showed a decreased Lys acetylation status of specific photosynthetic
proteins including PSI, PSII, and LHCII subunits. Our work demonstrates that the
chloroplast acetyltransferase NSI is needed for the dynamic reorganization of
thylakoid protein complexes during photosynthetic state transitions.
PMID- 29967053
TI - Genomics-Assisted Identification and Characterization of the Genetic Variants
Underlying Differential Nitrogen Use Efficiencies in Allotetraploid Rapeseed
Genotypes.
AB - Nitrogen (N) is a non-mineral macronutrient essential for plant growth and
development. Oilseed rape (AnAnCnCn, 2n = 4x = 38) has a high requirement for N
nutrients whereas showing the lowest N use efficiency (NUE) among crops. The
mechanisms underlying NUE regulation in Brassica napus remain unclear because of
genome complexity. In this study, we performed high-depth and -coverage whole
genome re-sequencing (WGS) of an N-efficient (higher NUE) genotype "XY15" and an
N-inefficient (lower NUE) genotype "814" of rapeseed. More than 687 million 150
bp paired-end reads were generated, which provided about 93% coverage and 50*
depth of the rapeseed genome. Applying stringent parameters, we identified a
total of 1,449,157 single-nucleotide polymorphisms (SNPs), 335,228 InDels,
175,602 structure variations (SVs) and 86,280 copy number variations (CNVs)
between the N-efficient and -inefficient genotypes. The largest proportion of
various DNA polymorphisms occurred in the inter-genic regions. Unlike CNVs, the
SNP/InDel and SV polymorphisms showed variation bias of the An and Cn subgenomes,
respectively. Gene ontology analysis showed the genetic variants were mapped onto
the genes involving N compound transport and ATPase complex metabolism, but not
including N assimilation-related genes. On basis of identification of N
starvation responsive genes through high-throughput expression profiling, we also
mapped these variants onto some key NUE-regulating genes, and validated their
significantly differential expression between the N-efficient and -inefficient
genotypes through qRT-PCR assays. Our data provide genome-wide high resolution
DNA variants underlying NUE divergence in allotetraploid rapeseed genotypes,
which would expedite the effective identification and functional validation of
key NUE-regulating genes through genomics-assisted improvement of crop nutrient
efficiency.
PMID- 29967055
TI - Social Aspects of Hookah Smoking Among US Youth.
AB - : : media-1vid110.1542/5789657771001PEDS-VA_2018-0341Video Abstract BACKGROUND:
We investigated 3 social dimensions of youth hookah smoking: frequency, places
smoked, and descriptive social norms. METHODS: Data were from the 2016 National
Youth Tobacco Survey of US sixth- to 12th-graders (n = 20 675). Hookah smoking
frequency was classified as never, former, current occasional, and current
frequent. Places where past 30-day hookah smoking occurred and students'
perceptions of their classmates' hookah smoking prevalence were assessed.
Descriptive and multivariable analyses were performed (P < .05). RESULTS:
Overall, 10.5% reported smoking hookah >=1 time in their lifetime. Of these,
65.8% were former, 26.3% were current occasional, and 7.9% were current frequent
smokers. Overall, 59.3% of students overestimated hookah smoking prevalence in
their grade. Current occasional smoking was predicted by female sex (adjusted
odds ratio [aOR] = 1.54) and peer hookah-smoking overestimation (aOR = 9.30).
Current frequent smoking was most strongly predicted by living with a hookah
smoker (aOR = 20.56), speaking a second language other than English (aOR = 2.17),
and co-use of mentholated cigarettes (aOR = 19.94) or other flavored noncigarette
tobacco products (aOR = 17.59). The top 3 places hookah was smoked were a
friend's house (47.7%), the respondent's own house (31.8%), and another family
member's house (20.8%). CONCLUSIONS: The home environment was the most common
place for youth hookah smoking. Home-tailored interventions that encourage
voluntary smoke-free rules and warn about the dangers of social smoking could
help denormalize hookah smoking.
PMID- 29967056
TI - Rural Versus Urban Hospitalizations for Firearm Injuries in Children and
Adolescents.
AB - : : media-1vid110.1542/5789654953001PEDS-VA_2017-3318Video Abstract OBJECTIVES:
Firearms are a leading cause of injury and death for children and adolescents in
the United States. We examined how hospitalization rates for firearm injuries
differ for rural and urban populations. METHODS: The Kids' Inpatient Database was
used to identify hospitalizations for firearm injuries in patients <20 years of
age by using International Classification of Diseases, Ninth Revision external
cause-of-injury codes. Data from 2006, 2009, and 2012 were analyzed to compare
demographics and intent (assault, self-inflicted, unintentional, and
undetermined). Urban-rural classification was based on patients' county of
residence. Rates were calculated by using weighted cases and US Census data.
RESULTS: There were 21 581 hospitalizations for firearm injuries. The overall
hospitalization rate was higher in urban versus rural areas (risk ratio [RR] =
1.95; 95% confidence interval [CI]: 1.81-2.10). Rates were highest for assaults
in urban 15- to 19-year-olds (RR = 7.82; 95% CI: 6.48-9.44). Unintentional
injuries were the leading cause of hospitalizations in younger age groups in all
urban and rural locations. Rates for unintentional injuries were lower among
urban versus rural 5- to 9-year-olds (RR = 0.47; 95% CI: 0.36-0.63) and 10- to 14
year-olds (RR = 0.44; 95% CI: 0.37-0.52). CONCLUSIONS: Hospitalizations for
firearm assaults among urban 15- to 19-year-olds represent the highest injury
rate. Notably, hospitalizations are lower for urban versus rural 5- to 9-year
olds and 10- to 14-year-olds, and unintentional firearm injuries are most common
among these groups. Preventative public health approaches should address these
differences in injury epidemiology.
PMID- 29967054
TI - Genome-Wide Association and Regional Heritability Mapping of Plant Architecture,
Lodging and Productivity in Phaseolus vulgaris.
AB - The availability of high-density molecular markers in common bean has allowed to
explore the genetic basis of important complex agronomic traits with increased
resolution. Genome-Wide Association Studies (GWAS) and Regional Heritability
Mapping (RHM) are two analytical approaches for the detection of genetic
variants. We carried out GWAS and RHM for plant architecture, lodging and
productivity across two important growing environments in Brazil in a germplasm
of 188 common bean varieties using DArTseq genotyping strategies. The coefficient
of determination of G * E interaction (c2int ) was equal to 17, 21 and 41%,
respectively for the traits architecture, lodging, and productivity. Trait
heritabilities were estimated at 0.81 (architecture), 0.79 (lodging) and 0.43
(productivity), and total genomic heritability accounted for large proportions
(72% to ~100%) of trait heritability. At the same probability threshold, three
marker-trait associations were detected using GWAS, while RHM detected eight QTL
encompassing 145 markers along five chromosomes. The proportion of genomic
heritability explained by RHM was considerably higher (35.48 to 58.02) than that
explained by GWAS (28.39 to 30.37). In general, RHM accounted for larger
fractions of the additive genetic variance being captured by markers effects
inside the defined regions. Nevertheless, a considerable proportion of the
heritability is still missing (~42% to ~64%), probably due to LD between markers
and genes and/or rare allele variants not sampled. RHM in autogamous species had
the potential to identify larger-effect QTL combining allelic variants that could
be effectively incorporated into whole-genome prediction models and tracked
through breeding generations using marker-assisted selection.
PMID- 29967057
TI - One Hundred Years of Linkage Disequilibrium.
AB - One hundred years ago, the first population genetic calculations were made for
two loci. They indicated that populations should settle down to a state where the
frequency of an allele at one locus is independent of the frequency of an allele
at a second locus, even if these loci are linked. Fifty years later it was
realized what is obvious in retrospect, that these calculations ignored the
effect of chance segregation of linked loci, an effect now widely recognized
following the association of closely linked markers (SNPs) with rare genetic
diseases. Linkage disequilibrium is now accepted as the norm for closely linked
loci, leading to powerful applications in the mapping of disease alleles and
quantitative trait loci, in the detection of sites of selection in the human
genome, in the application of genomic prediction of quantitative traits in animal
and plant breeding, in the estimation of population size, and in the dating of
population divergence.
PMID- 29967058
TI - Investigating Potassium Channels in Budding Yeast: A Genetic Sandbox.
AB - Like all species, the model eukaryote Saccharomyces cerevisiae, or Bakers' yeast,
concentrates potassium in the cytosol as an electrogenic osmolyte and enzyme
cofactor. Yeast are capable of robust growth on a wide variety of potassium
concentrations, ranging from 10 uM to 2.5 M, due to the presence of a high
affinity potassium uptake system and a battery of cation exchange transporters.
Genetic perturbation of either of these systems retards yeast growth on low or
high potassium, respectively. However, these potassium-sensitized yeast are a
powerful genetic tool, which has been leveraged for diverse studies. Notably, the
potassium-sensitive cells can be transformed with plasmids encoding potassium
channels from bacteria, plants, or mammals, and subsequent changes in growth rate
have been found to correlate with the activity of the introduced potassium
channel. Discoveries arising from the use of this assay over the past three
decades have increased our understanding of the structure-function relationships
of various potassium channels, the mechanisms underlying the regulation of
potassium channel function and trafficking, and the chemical basis of potassium
channel modulation. In this article, we provide an overview of the major genetic
tools used to study potassium channels in S. cerevisiae, a survey of seminal
studies utilizing these tools, and a prospective for the future use of this
elegant genetic approach.
PMID- 29967060
TI - Bioinformat-Eggs: An Educational Primer for Use with "LIN-41 and OMA
Ribonucleoprotein Complexes Mediate a Translational Repression-to-Activation
Switch Controlling Oocyte Meiotic Maturation and the Oocyte-to-Embryo Transition
in Caenorhabditis elegans".
AB - High-throughput sequencing and bioinformatic techniques have enhanced classical
genetic analysis and are essential methods for geneticists. Tsukamoto and
colleagues use numerous genomic and bioinformatics methods to explore the role of
ribonucleoprotein complexes in regulating oocyte meiotic maturation, which is the
transition between diakinesis and metaphase of meiosis I. This primer provides
guidance for both educators and students as they read "LIN-41 and OMA
Ribonucleoprotein Complexes Mediate a Translational Repression-to-Activation
Switch Controlling Oocyte Meiotic Maturation and the Oocyte-to-Embryo Transition
in Caenorhabditis elegans" The primer provides background information on the
utility of the C. elegans germ line as a model for meiotic regulation, and
further describes methods of bioinformatic analysis used to study translational
and post-translational gene regulation. Additionally, the primer provides
discussion questions and an active learning exercise designed to enhance student
learning of critical genetic concepts.
PMID- 29967062
TI - Quantifying compartment-associated variations of protein abundance in proteomics
data.
AB - Quantitative mass spectrometry enables to monitor the abundance of thousands of
proteins across biological conditions. Currently, most data analysis approaches
rely on the assumption that the majority of the observed proteins remain
unchanged across compared samples. Thus, gross morphological differences between
cell states, deriving from, e.g., differences in size or number of organelles,
are often not taken into account. Here, we analyzed multiple published datasets
and frequently observed that proteins associated with a particular cellular
compartment collectively increase or decrease in their abundance between
conditions tested. We show that such effects, arising from underlying
morphological differences, can skew the outcome of differential expression
analysis. We propose a method to detect and normalize morphological effects
underlying proteomics data. We demonstrate the applicability of our method to
different datasets and biological questions including the analysis of sub
cellular proteomes in the context of Caenorhabditis elegans aging. Our method
provides a complementary perspective to classical differential expression
analysis and enables to uncouple overall abundance changes from stoichiometric
variations within defined group of proteins.
PMID- 29967059
TI - Recent Molecular Genetic Explorations of Caenorhabditis elegans MicroRNAs.
AB - MicroRNAs are small, noncoding RNAs that regulate gene expression at the post
transcriptional level in essentially all aspects of Caenorhabditis elegans
biology. More than 140 genes that encode microRNAs in C. elegans regulate
development, behavior, metabolism, and responses to physiological and
environmental changes. Genetic analysis of C. elegans microRNA genes continues to
enhance our fundamental understanding of how microRNAs are integrated into
broader gene regulatory networks to control diverse biological processes,
including growth, cell division, cell fate determination, behavior, longevity,
and stress responses. As many of these microRNA sequences and the related
processing machinery are conserved over nearly a billion years of animal
phylogeny, the assignment of their functions via worm genetics may inform the
functions of their orthologs in other animals, including humans. In vivo
investigations are especially important for microRNAs because in silico
extrapolation of their functions using mRNA target prediction programs can easily
assign microRNAs to incorrect genetic pathways. At this mezzanine level of
microRNA bioinformatic sophistication, genetic analysis continues to be the gold
standard for pathway assignments.
PMID- 29967063
TI - Structural and functional analysis of cystatin E reveals enzymologically relevant
dimer and amyloid fibril states.
AB - Protein activity is often regulated by altering the oligomerization state. One
mechanism of multimerization involves domain swapping, wherein proteins exchange
parts of their structures and thereby form long-lived dimers or multimers. Domain
swapping has been specifically observed in amyloidogenic proteins, for example
the cystatin superfamily of cysteine protease inhibitors. Cystatins are twin
headed inhibitors, simultaneously targeting the lysosomal cathepsins and
legumain, with important roles in cancer progression and Alzheimer's disease.
Although cystatin E is the most potent legumain inhibitor identified so far,
nothing is known about its propensity to oligomerize. In this study, we show that
conformational destabilization of cystatin E leads to the formation of a domain
swapped dimer with increased conformational stability. This dimer was active as a
legumain inhibitor by forming a trimeric complex. By contrast, the binding sites
toward papain-like proteases were buried within the cystatin E dimer. We also
showed that the dimers could further convert to amyloid fibrils. Unexpectedly,
cystatin E amyloid fibrils contained functional protein, which inhibited both
legumain and papain-like enzymes. Fibril formation was further regulated by
glycosylation. We speculate that cystatin amyloid fibrils might serve as a
binding platform to stabilize the pH-sensitive legumain and cathepsins in the
extracellular environment, contributing to their physiological and pathological
functions.
PMID- 29967064
TI - Transcription factor-7-like 2 (TCF7L2) gene acts downstream of the Lkb1/Stk11
kinase to control mTOR signaling, beta cell growth, and insulin secretion.
AB - Variants in the transcription factor-7-like 2 (TCF7L2/TCF4) gene, involved in Wnt
signaling, are associated with type 2 diabetes. Loss of Tcf7l2 selectively from
the beta cell in mice has previously been shown to cause glucose intolerance and
to lower beta cell mass. Deletion of the tumor suppressor liver kinase B1
(LKB1/STK11) leads to beta cell hyperplasia and enhanced glucose-stimulated
insulin secretion, providing a convenient genetic model for increased beta cell
growth and function. The aim of this study was to explore the possibility that
Tcf7l2 may be required for the effects of Lkb1 deletion on insulin secretion in
the mouse beta cell. Mice bearing floxed Lkb1 and/or Tcf7l2 alleles were bred
with knockin mice bearing Cre recombinase inserted at the Ins1 locus (Ins1Cre),
allowing highly beta cell-selective deletion of either or both genes. Oral
glucose tolerance was unchanged by the further deletion of a single Tcf7l2 allele
in these cells. By contrast, mice lacking both Tcf7l2 alleles on this background
showed improved oral glucose tolerance and insulin secretion in vivo and in vitro
compared with mice lacking a single Tcf7l2 allele. Biallelic Tcf7l2 deletion also
enhanced beta cell proliferation, increased beta cell mass, and caused changes in
polarity as revealed by the "rosette-like" arrangement of beta cells. Tcf7l2
deletion also increased signaling by mammalian target of rapamycin (mTOR),
augmenting phospho-ribosomal S6 levels. We identified a novel signaling mechanism
through which a modifier gene, Tcf7l2, lies on a pathway through which LKB1 acts
in the beta cell to restrict insulin secretion.
PMID- 29967065
TI - The carbohydrate-binding module and linker of a modular lytic polysaccharide
monooxygenase promote localized cellulose oxidation.
AB - Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that
catalyze the oxidative cleavage of polysaccharides such as cellulose and chitin,
a feature that makes them key tools in industrial biomass conversion processes.
The catalytic domains of a considerable fraction of LPMOs and other carbohydrate
active enzymes (CAZymes) are tethered to carbohydrate-binding modules (CBMs) by
flexible linkers. These linkers preclude X-ray crystallographic studies, and the
functional implications of these modular assemblies remain partly unknown. Here,
we used NMR spectroscopy to characterize structural and dynamic features of full
length modular ScLPMO10C from Streptomyces coelicolor We observed that the linker
is disordered and extended, creating distance between the CBM and the catalytic
domain and allowing these domains to move independently of each other. Functional
studies with cellulose nanofibrils revealed that most of the substrate-binding
affinity of full-length ScLPMO10C resides in the CBM. Comparison of the catalytic
performance of full-length ScLPMO10C and its isolated catalytic domain revealed
that the CBM is beneficial for LPMO activity at lower substrate concentrations
and promotes localized and repeated oxidation of the substrate. Taken together,
these results provide a mechanistic basis for understanding the interplay between
catalytic domains linked to CBMs in LPMOs and CAZymes in general.
PMID- 29967066
TI - Force-activated catalytic pathway accelerates bacterial adhesion against flow.
AB - Mechanical cues often influence the factors affecting the transition states of
catalytic reactions and alter the activation pathway. However, tracking the real
time dynamics of such activation pathways is limited. Using single-molecule
trapping of reaction intermediates, we developed a method that enabled us to
perform one reaction at one site and simultaneously study the real-time dynamics
of the catalytic pathway. Using this, we showed single-molecule calligraphy at
nanometer resolution and deciphered the mechanism of the sortase A enzymatic
reaction that, counter-intuitively, accelerates bacterial adhesion under shear
tension. Our method captured a force-induced dissociation of the enzyme-substrate
bond that accelerates the forward reaction 100*, proposing a new mechano
activated catalytic pathway. In corroboration, our molecular dynamics simulations
in the presence of force identified a force-induced conformational switch in the
enzyme that accelerates proton transfer between CYS184 (acceptor) and HIS120
(donor) catalytic dyads by reducing the inter-residue distances. Overall, the
present study opens up the possibility of studying the influence of factors
affecting transition states in real time and paves the way for the rational
design of enzymes with enhanced efficiency.
PMID- 29967067
TI - Evidence for substrate-assisted catalysis in N-acetylphosphoglucosamine mutase.
AB - N-acetylphosphoglucosamine mutase (AGM1) is a key component of the hexosamine
biosynthetic pathway that produces UDP-GlcNAc, an essential precursor for a wide
range of glycans in eukaryotes. AGM belongs to the alpha-d-phosphohexomutase
metalloenzyme superfamily and catalyzes the interconversion of N
acetylglucosamine-6-phosphate (GlcNAc-6P) to N-acetylglucosamine-1-phosphate
(GlcNAc-1P) through N-acetylglucosamine-1,6-bisphosphate (GlcNAc-1,6-bisP) as the
catalytic intermediate. Although there is an understanding of the phosphoserine
dependent catalytic mechanism at enzymatic and structural level, the identity of
the requisite catalytic base in AGM1/phosphoglucomutases is as yet unknown. Here,
we present crystal structures of a Michaelis complex of AGM1 with GlcNAc-6P and
Mg2+, and a complex of the inactive Ser69Ala mutant together with glucose-1,6
bisphosphate (Glc-1,6-bisP) that represents key snapshots along the reaction co
ordinate. Together with mutagenesis, these structures reveal that the phosphate
group of the hexose-1,6-bisP intermediate may act as the catalytic base.
PMID- 29967068
TI - HIF-1alpha activation in myeloid cells accelerates dextran sodium sulfate-induced
colitis progression in mice.
AB - Inflammatory bowel disease (IBD) is a chronic inflammatory disease, in which the
intestinal epithelium loses its barrier function. Given the existence of the
oxygen gradient in the intestinal epithelium and that inflammation further
contributes to the tissue hypoxia, we investigated the role of hypoxia-inducible
factor (HIF), a transcription factor activated under hypoxic conditions in
myeloid cells, in the progression of IBD. To do this, we utilized myeloid
specific knockout (KO) mice targeting HIF pathways, created by a Cre-loxP system
with human MRP8 (hMRP8), an intracellular calcium-binding protein, as the myeloid
promoter. By feeding 5% dextran sodium sulfate (DSS) to hMRP8 von Hippel Lindau
(Vhl) KO mice, in which HIF-1alpha and HIF-2alpha are constitutively activated in
myeloid cells, we found that these mice were highly susceptible to DSS-induced
colitis, demonstrating greater body weight loss, increased mortality, faster
onset of rectal bleeding, shortened colon length, and increased CD11b- or Gr-1
positive myeloid cells in the colon compared with wild-type (WT) mice. These
parameters were restored to, if not better than, the WT levels when we examined
hMRP8 Hif-1a KO mice upon 5% DSS feeding. hMRP8 Hif-2a KO mice, on the other
hand, exhibited a similar degree of DSS-induced colitis to that of WT mice.
Lastly, when DSS was given together with azoxymethane to induce tumorigenesis in
the colon, we found that hMRP8 Hif-1a KO mice exhibited comparable levels of
colorectal tumors to those of WT mice, indicating that HIF-1alpha in myeloid
cells is dispensable for tumorigenesis. Collectively, our results suggest that
HIF-1alpha activation in myeloid cells critically regulates IBD progression.
PMID- 29967073
TI - Epistatic Oncogenic Interactions Determine Cancer Susceptibility to
Immunotherapy.
AB - Cancer genetic alterations and epigenetics control the malignant phenotype of
tumor cells and the stroma. Synergistic oncogenic alterations may cooperatively
dictate immunogenicity, level of infiltration by immune system cells, and
response to immunotherapy in an epistatic fashion. The work of Skoulidis and
colleagues shows that concomitant RAS and STK11/LKB1 mutations in non-small cell
lung adenocarcinomas result in primary resistance to PD-1-based immunotherapy and
poor T-cell infiltration. Cancer Discov; 8(7); 794-6. (c)2018 AACRSee related
article by Skoulidis et al., p. 822.
PMID- 29967074
TI - Stop fRETting the Target: Next-Generation RET Inhibitors Have Arrived.
AB - BLU-667 is a next-generation RET inhibitor that maximizes on-target and
minimizes off-target effects. It is an exemplar of genotype-driven drug
development followed by multi-histology basket trial validation that is becoming
a paradigm for precision oncology. Cancer Discov; 8(7); 797-9. (c)2018 AACRSee
related article by Subbiah et al., p. 836.
PMID- 29967069
TI - A carcinogenic trigger to study the function of tumor suppressor genes in
Schmidtea mediterranea.
AB - Planarians have been long known for their regenerative ability, which hinges on
pluripotency. Recently, however, the planarian model has been successfully
established for routine toxicological screens aimed to assess overproliferation,
mutagenicity and tumorigenesis. In this study, we focused on planarian tumor
suppressor genes (TSGs) and their role during chemically induced carcinogenic
stress in Schmidtea mediterranea Combining in silico and proteomic screens with
exposure to human carcinogen type 1A agent cadmium (Cd), we showed that many TSGs
have a function in stem cells and that, in general, exposure to Cd accelerated
the onset and increased the severity of the observed phenotype. This suggested
that the interaction between environmental and genetic factors plays an important
role in tumor development in S. mediterranea Therefore, we further focused on the
synergistic effects of Cd exposure and p53 knockdown (KD) at the cellular and
molecular levels. Cd also produced a specific proteomic landscape in homeostatic
animals, with 172 proteins differentially expressed, 43 of which were
downregulated. Several of these proteins have tumor suppressor function in human
and other animals, namely Wilms Tumor 1 Associated Protein (WT1), Heat Shock
Protein 90 (HSP90), Glioma Pathogenesis-Related Protein 1 (GLIPR1) and Matrix
Metalloproteinase B (Smed-MMPB). Both Glipr1 and MmpB KD produced large
outgrowths, epidermal lesions and epidermal blisters. The epidermal blisters that
formed as a consequence of Smed-MmpB KD were populated by smedwi1+ cells, many of
which were actively proliferating, while large outgrowths contained ectopically
differentiated structures, such as photoreceptors, nervous tissue and a small
pharynx. In conclusion, Smed-MmpB is a planarian TSG that prevents stem cell
proliferation and differentiation outside the proper milieu.
PMID- 29967075
TI - Macropinocytosis Fuels Prostate Cancer.
AB - Kim and colleagues identify necrotic debris as a macropinocytic cargo in PTEN
deficient prostate cancer cells, which is catabolized to generate the nutrients
and biomass necessary to support tumor cell growth and metabolism in nutrient
limiting conditions. Cancer Discov; 8(7); 800-2. (c)2018 AACR.See related article
by Kim et al., p. 866.
PMID- 29967076
TI - Corrigendum.
PMID- 29967077
TI - Genetic Counseling in Pediatrics.
AB - Genetic counseling is a communication process whereby an individual or family
obtains information about a genetic condition, is helped to understand the
implications and significance of the condition, and is given resources to help
with coping and management. It is a continuous process involving lasting
supportive relationships between the family and the genetic professional. Genetic
counselors are master's level-trained health-care professionals who work closely
with pediatricians and pediatric subspecialists alike. Genetic counselors can be
a source of information about genetic conditions, risk assessment for disease,
and genetic testing. Although most of a genetic counselor's job is patient care
and education, genetic counselors also serve as resources to educate health
professionals about genetics.
PMID- 29967078
TI - Disorders of the Umbilical Cord.
AB - The umbilical cord, a vital conduit between the placenta and the fetus, loses
much of its significance after birth. However, newborns can often present with
various abnormalities of the umbilicus, such as benign granulomas or more serious
lesions due to persistent remnants, many of which can change the normal course of
cord separation and may be associated with significant morbidities if left
unrecognized and uncorrected. Although not uncommon, sanguineous drainage from
the umbilical stump can be quite alarming to new parents. Parental counseling
regarding normal umbilical cord changes, as well as abnormal findings, such as
discharge and skin changes, are important for the recognition and timely
treatment of potentially significant umbilical cord disorders.
PMID- 29967079
TI - Vomiting in Children.
PMID- 29967080
TI - Case 1: Microcephaly, Skeletal Dysplasia, and Immunodeficiency in a Newborn.
PMID- 29967081
TI - Case 2: 3-month-old Boy with Micropenis.
PMID- 29967082
TI - Case 3: Skull Depression in a 9-month-old Girl.
PMID- 29967083
TI - Case 4: Recurrent Orange Urine and Abdominal Pain in a 13-year-old Boy.
PMID- 29967084
TI - Safety: Texting while Driving.
PMID- 29967087
TI - SGA and VLBW Infants: Outcomes and Care.
PMID- 29967088
TI - Visual Diagnosis: A Ring of Long, Dark, Coarse Hair on the Scalp of a 5-month-old
Girl.
PMID- 29967089
TI - PD-L1, TIM-3, and CTLA-4 blockade fail to promote resistance to secondary
infection with virulent strains of Toxoplasma gondii.
AB - T cell exhaustion is a state of hyporesponsiveness that develops during many
chronic infections and cancer. Neutralization of inhibitory receptors, or
'checkpoint blockade', can reverse T cell exhaustion and lead to beneficial
prognoses in experimental and clinical settings. Whether checkpoint blockade can
resolve lethal acute infections is less understood, but may be beneficial in
vaccination protocols that fail to elicit sterilizing immunity. Since a fully
protective vaccine for any human parasite has yet to be developed, we explored
the efficacy of checkpoint inhibitors in a mouse model of Toxoplasma gondii re
infection. Mice chronically infected with an avirulent type III strain survive
reinfection with the type I RH but not MAS, GUY-DOS and GT1 parasite strains. We
report here that mouse susceptibility to secondary infection correlates with
initial parasite burden and that protection to the RH strain is dependent on CD8
but not CD4 T cells in this model. When given a lethal secondary infection, CD8
and CD4 T cells upregulate several co-inhibitory receptors including PD-1, TIM-3,
4-1bb and CTLA-4. Moreover, CD8 but not CD4 T cells are significantly reduced in
their IFNgamma response during secondary infection with virulent strains,
suggesting checkpoint blockade may reduce disease severity. However, single and
combination therapies targeting TIM-3, CTLA-4, and/or PD-L1 failed to reverse
susceptibility to secondary infection. These results suggest that additional host
responses, which are refractory to checkpoint blockade, are likely required for
immunity to this pathogen.
PMID- 29967090
TI - Secreted Phosphatase and Deoxyribonuclease Are Required by Pseudomonas aeruginosa
To Defend against Neutrophil Extracellular Traps.
AB - Neutrophil extracellular traps (NETs) are produced by neutrophils as an innate
immune defense mechanism to trap and kill microbial pathogens. NETs are comprised
of ejected chromatin that forms a lattice structure enmeshed with numerous
antimicrobial proteins. In addition to forming the structural backbone of NETs,
extracellular DNA (eDNA) has membrane-disrupting antimicrobial activity that
contributes to NET killing. Many pathogens produce secreted extracellular DNases
to evade the antimicrobial activity of NETs. Pseudomonas aeruginosa encodes an
operon of two secreted enzymes, a predicted alkaline phosphatase and a DNase. The
DNase (eddB) degrades eDNA to use as a nutrient source. Here we report that both
eDNA and NETs are potent inducers of this DNase-phosphatase operon. Furthermore,
the secreted DNase contributes to degrading NET DNA and defends P. aeruginosa
against NET-mediated killing. We demonstrate that EddA has both alkaline
phosphatase and phosphodiesterase (PDase) activities and also protects against
the antimicrobial activity of NETs. Although the phosphatase does not cause DNA
degradation similar to that of the DNase, its protective function is likely a
result of removing the cation-chelating phosphates from the eDNA phosphodiester
backbone. Therefore, both the DNase and PDase contribute to defense against NET
killing of P. aeruginosa, highlighting the role of DNA-manipulating enzymes in
targeting the eDNA in neutrophil extracellular traps.
PMID- 29967091
TI - Plasmodium vivax Merozoite Surface Protein 1 Paralog as a Mediator of Parasite
Adherence to Reticulocytes.
AB - Plasmodium vivax parasites preferentially invade reticulocytes in human beings.
P. vivax merozoite surface protein 1 (PvMSP1) and PvMSP1 paralog (PvMSP1P) may
have important functions in reticulocyte adherence during invasion. These
proteins share similar structures, including the presence of two epidermal growth
factor (EGF)-like and glycosylphosphatidylinositol (GPI)-anchored domains at the
C terminus. However, there have been no reports concerning the functional
activity of PvMSP1P in reticulocyte adherence during P. vivax invasion. In this
study, the ability of PvMSP1P-19 to bind to reticulocytes and normocytes was
analyzed. The reticulocyte binding activity of PvMSP1P-19 was 4.0-fold higher
than its normocyte binding activity. The binding of PvMSP1P-19 to reticulocytes
and normocytes was inhibited in a dose-dependent manner by antibodies from
immunized rabbits and by antibodies from vivax parasite-infected patients.
Consistently, antibodies against PvMSP1P inhibited parasite invasion during short
term in vitro cultivation. Similar to the case for PvDBPII binding activity,
PvMSP1P-19 binding activity was reduced in chymotrypsin-treated reticulocytes.
However, no significant difference between the binding of PvMSP1P-19 to Duffy
positive and Duffy-negative erythrocytes was found. The minimal binding motif of
PvMSP1P-19 was characterized using synthetic peptides. The results showed that
the residues at amino acid positions 1791 to 1808 may have an important function
in mediating merozoite adherence to reticulocytes. The positively charged
residues within the EGF-like domain were shown to constitute a key binding motif.
This work presents strong evidence supporting the role of PvMSP1P in host target
cell selection and invasion of Duffy-independent pathway in P. vivax Moreover,
PvMSP1P-19-specific antibodies may confer protection against P. vivax reinvasion.
PMID- 29967093
TI - Transgenic Eimeria tenella Expressing Profilin of Eimeria maxima Elicits Enhanced
Protective Immunity and Alters Gut Microbiome of Chickens.
AB - Coccidiosis is one of the most serious diseases of livestock and birds in the
world. Vaccination with live-parasite anticoccidial vaccines with genetic
manipulation improving the immunogenicity of vaccine strains would be the best
means for controlling coccidiosis in breeder and layer stocks, even in fast
growing broilers. Profilin from apicomplexan parasites is the first molecularly
defined ligand for Toll-like receptor 11 (TLR11) and TLR12 in mice and is a
potential molecular adjuvant. Here, we constructed a transgenic Eimeria tenella
line (Et-EmPro) expressing the profilin of Eimeria maxima, the most immunogenic
species of chicken coccidia, and evaluated the adjuvant effects of EmPro on the
immunogenicity of E. tenella We found that immunization with the transgenic
Eimeria parasites, compared with the wild type, elicited greater parasite antigen
specific cell-mediated immunity, characterized by increased numbers of interferon
gamma (IFN-gamma)-secreting lymphocytes. The transgenic parasite also induced
better protective immunity against E. tenella challenge than the wild type. In
addition, the diversity of the fecal microbiome of the birds immunized with the
transgenic parasite differed from that of the microbiome of the wild-type
immunized birds, indicating interactions of Eimeria with the gut microbiome of
chickens. Our results showing enhanced immunogenicity of E. tenella by use of
EmPro as a molecular adjuvant derived from the most immunogenic affinis species
represent a large step forward in the development of the next generation of
coccidiosis vaccines using Eimeria as a vaccine platform expressing molecular
adjuvants and potentially other pathogen antigens against not only coccidiosis
but also other infectious diseases.
PMID- 29967092
TI - The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell
Translatome.
AB - The intracellular parasite Toxoplasma gondii promotes infection by targeting
multiple host cell processes; however, whether it modulates mRNA translation is
currently unknown. Here, we show that infection of primary murine macrophages
with type I or II T. gondii strains causes a profound perturbation of the host
cell translatome. Notably, translation of transcripts encoding proteins involved
in metabolic activity and components of the translation machinery was activated
upon infection. In contrast, the translational efficiency of mRNAs related to
immune cell activation and cytoskeleton/cytoplasm organization was largely
suppressed. Mechanistically, T. gondii bolstered mechanistic target of rapamycin
(mTOR) signaling to selectively activate the translation of mTOR-sensitive mRNAs,
including those with a 5'-terminal oligopyrimidine (5' TOP) motif and those
encoding mitochondrion-related proteins. Consistent with parasite modulation of
host mTOR-sensitive translation to promote infection, inhibition of mTOR activity
suppressed T. gondii replication. Thus, selective reprogramming of host mRNA
translation represents an important subversion strategy during T. gondii
infection.
PMID- 29967094
TI - Terminal Deoxynucleotidyl Transferase Is Not Required for Antibody Response to
Polysaccharide Vaccines against Streptococcus pneumoniae and Salmonella enterica
Serovar Typhi.
AB - B cell antigen receptor (BCR) diversity increases by several orders of magnitude
due to the action of terminal deoxynucleotidyl transferase (TdT) during V(D)J
recombination. Unlike adults, infants have limited BCR diversity, in part due to
reduced expression of TdT. Since human infants and young mice respond poorly to
polysaccharide vaccines, such as the pneumococcal polysaccharide vaccine
Pneumovax23 and Vi polysaccharide (ViPS) of Salmonella enterica serovar Typhi, we
tested the contribution of TdT-mediated BCR diversity in response to these
vaccines. We found that TdT+/- and TdT-/- mice generated comparable antibody
responses to Pneumovax23 and survived Streptococcus pneumoniae challenge.
Moreover, passive immunization of B cell-deficient mice with serum from
Pneumovax23-immunized TdT+/- or TdT-/- mice conferred protection. TdT+/- and TdT
/- mice generated comparable levels of anti-ViPS antibodies and antibody
dependent, complement-mediated bactericidal activity against S Typhi in vitro To
test the protective immunity conferred by ViPS immunization in vivo, TdT+/- and
TdT-/- mice were challenged with a chimeric Salmonella enterica serovar
Typhimurium strain expressing ViPS, since mice are nonpermissive hosts for S
Typhi infection. Compared to their unimmunized counterparts, immunized TdT+/- and
TdT-/- mice challenged with ViPS-expressing S Typhimurium exhibited a significant
reduction in the bacterial burden and liver pathology. These data suggest that
the impaired antibody response to the Pneumovax23 and ViPS vaccines in the young
is not due to limited TdT-mediated BCR diversification.
PMID- 29967095
TI - Gene Regulation by Redox-Sensitive Burkholderia thailandensis OhrR and Its Role
in Bacterial Killing of Caenorhabditis elegans.
AB - Fatty acid hydroperoxides are involved in host-pathogen interactions. In both
plants and mammals, polyunsaturated fatty acids are liberated during infection
and enzymatically oxidized to the corresponding toxic hydroperoxides during the
defensive oxidative burst that is designed to thwart the infection. The bacterial
transcription factor OhrR (organic hydroperoxide reductase regulator) is oxidized
by organic hydroperoxides, as a result of which the ohr gene encoding organic
hydroperoxide reductase is induced. This enzyme converts the hydroperoxides to
less toxic alcohols. We show here that OhrR from Burkholderia thailandensis
represses expression of ohr Gene expression is induced by cumene hydroperoxide
and to a lesser extent by inorganic oxidants; however, Ohr contributes to
degradation only of the organic hydroperoxide. B. thailandensis OhrR, which binds
specific sites in both ohr and ohrR promoters, as evidenced by DNase I
footprinting, belongs to the 2-Cys subfamily of OhrR proteins, and its oxidation
leads to reversible disulfide bond formation between conserved N- and C-terminal
cysteines in separate monomers. Oxidation of the N-terminal Cys is sufficient for
attenuation of DNA binding in vitro, with complete restoration of DNA binding
occurring on addition of a reducing agent. Surprisingly, both overexpression of
ohr and deletion of ohr results in enhanced survival on exposure to organic
hydroperoxide in vitro While Deltaohr cells are more virulent in a Caenorhabditis
elegans model of infection, DeltaohrR cells are less so. Taken together, our data
suggest that B. thailandensis OhrR has several unconventional features and that
both OhrR and organic hydroperoxides may contribute to virulence.
PMID- 29967096
TI - Jasmone Hydroxylase, a Key Enzyme in the Synthesis of the Alcohol Moiety of
Pyrethrin Insecticides.
AB - Pyrethrins are synthesized by the plant pyrethrum (Tanacetum cinerariifolium), a
chrysanthemum relative. These compounds possess efficient insecticidal properties
and are not toxic to humans and most vertebrates. Pyrethrum flowers, and to a
smaller extent leaves, synthesize six main types of pyrethrins, which are all
esters of a monoterpenoid acid moiety and an alcohol moiety derived from jasmonic
acid. Here, we identified and characterized the enzyme responsible for the
conversion of jasmone, a derivative of jasmonic acid, to jasmolone. Feeding
pyrethrum flowers with jasmone resulted in a 4-fold increase in the concentration
of free jasmolone as well as smaller but significant proportional increases in
free pyrethrolone and all three type I pyrethrins. We used floral transcriptomic
data to identify cytochrome P450 genes whose expression patterns were most highly
correlated with that of a key gene in pyrethrin biosynthesis, T. cinerariifolium
chrysanthemyl diphosphate synthase The candidate genes were screened for jasmone
hydroxylase activity through transient expression in Nicotiana benthamiana leaves
fed with jasmone. The expression of only one of these candidate genes produced
jasmolone; therefore, this gene was named T. cinerariifolium jasmolone
hydroxylase (TcJMH) and given the CYP designation CYP71AT148. The protein encoded
by TcJMH localized to the endoplasmic reticulum, and microsomal preparations from
N. benthamiana leaves expressing TcJMH were capable of catalyzing the
hydroxylation of jasmone to jasmolone in vitro, with a Km value of 53.9 um TcJMH
was expressed almost exclusively in trichomes of floral ovaries and was induced
in leaves by jasmonate.
PMID- 29967098
TI - Erratum: Metastases in Prostate Cancer.
PMID- 29967097
TI - The PILNCR1-miR399 Regulatory Module Is Important for Low Phosphate Tolerance in
Maize.
AB - The regulation of adaptive responses to phosphorus (P) deficiency by the
microRNA399 (miR399)/PHOSPHATE2 (PHO2) pathway has been well studied in
Arabidopsis (Arabidopsis thaliana) but not in maize (Zea mays). Here, we show
that miR399 transcripts are strongly induced in maize by phosphate (Pi)
deficiency. Transgenic maize plants that overexpressed MIR399b accumulated
excessive amounts of P in their shoots and displayed typical Pi-toxicity
phenotypes. We reannotated ZmPHO2 with an additional 1,165 bp of the 5'
untranslated region. miR399-guided posttranscriptional repression of ZmPHO2 was
mainly observed in the P-efficient lines. We identified Pi-deficiency-induced
long-noncoding RNA1 (PILNCR1) from our strand-specific RNA libraries. Transient
expression assays in Nicotiana benthamiana and maize leaf protoplasts
demonstrated that PILNCR1 inhibits ZmmiR399-guided cleavage of ZmPHO2 The
abundance of PILNCR1 was significantly higher in P-inefficient lines than in P
efficient lines, which is consistent with the abundance of ZmmiR399 transcripts.
These results indicate that the interaction between PILNCR1 and miR399 is
important for tolerance to low Pi in maize.
PMID- 29967099
TI - Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune
System in a Prenatal Immune Activation Model of Autism.
AB - Recent studies suggest that autism is often associated with dysregulated immune
responses and altered microbiota composition. This has led to growing speculation
about potential roles for hyperactive immune responses and the microbiome in
autism. Yet how microbiome-immune cross-talk contributes to neurodevelopmental
disorders currently remains poorly understood. In this study, we report critical
roles for prenatal microbiota composition in the development of behavioral
abnormalities in a murine maternal immune activation (MIA) model of autism that
is driven by the viral mimetic polyinosinic-polycytidylic acid. We show that
preconception microbiota transplantation can transfer susceptibility to MIA
associated neurodevelopmental disease and that this is associated with modulation
of the maternal immune response. Furthermore, we find that ablation of IL-17a
signaling provides protection against the development of neurodevelopmental
abnormalities in MIA offspring. Our findings suggest that microbiota landscape
can influence MIA-induced neurodevelopmental disease pathogenesis and that this
occurs as a result of microflora-associated calibration of gestational IL-17a
responses.
PMID- 29967101
TI - Rhabdovirus-Inducible MicroRNA-210 Modulates Antiviral Innate Immune Response via
Targeting STING/MITA in Fish.
AB - Viral infection induces type I IFN production, which plays critical roles in
orchestrating the antiviral defense by inducing direct antiviral activities. To
establish a persistent infection, viruses have evolved numerous strategies to
specifically interfere with IFN production or its downstream mediators, thereby
evading the immune responses. MicroRNAs (miRNAs) are a family of small noncoding
RNAs that posttranscriptionally regulate the expressions of specific target
genes. Although accumulating evidence demonstrates that miRNAs play vital roles
in regulating viral infection, miRNAs that target intracellular sensors and
adaptors of innate immunity have not been fully uncovered. In this paper, we
identify fish miR-210 as a robust regulator involved in regulating virus-host
interactions. We found that rhabdovirus significantly upregulated the expression
of fish miR-210. Inducible miR-210 modulates virus-triggered type I IFN and
inflammatory cytokine production by targeting stimulator of IFN genes (STING),
thereby promoting viral replication. Furthermore, we demonstrated that miR-210
regulates innate immune response through NF-kappaB, IFN regulatory factor 3, and
JAK/STAT signaling pathways. The collective findings indicate that inducible miR
210 plays a regulatory role in virus-host interactions through STING-mediated
singling pathway by targeting STING.
PMID- 29967100
TI - miR-155 Modulates Cockroach Allergen- and Oxidative Stress-Induced Cyclooxygenase
2 in Asthma.
AB - Exposure to cockroach allergen is a strong risk factor for developing asthma.
Asthma has been associated with allergen-induced airway epithelial damage and
heightened oxidant stress. In this study, we investigated cockroach allergen
induced oxidative stress in airway epithelium and its underlying mechanisms. We
found that cockroach extract (CRE) could induce reactive oxygen species (ROS)
production, particularly mitochondrial-derived ROS, in human bronchial epithelial
cells. We then used the RT2 Profiler PCR array and identified that cyclooxygenase
2 (COX-2) was the most significantly upregulated gene related to CRE-induced
oxidative stress. miR-155, predicted to target COX-2, was increased in CRE
treated human bronchial epithelial cells, and was showed to regulate COX-2
expression. Moreover, miR-155 can bind COX-2, induce COX-2 reporter activity, and
maintain mRNA stability. Furthermore, CRE-treated miR-155-/- mice showed reduced
levels of ROS and COX-2 expression in lung tissues and PGE2 in bronchoalveolar
lavage fluid compared with wild-type mice. These miR-155-/- mice also showed
reduced lung inflammation and Th2/Th17 cytokines. In contrast, when miR-155-/-
mice were transfected with adeno-associated virus carrying miR-155, the
phenotypic changes in CRE-treated miR-155-/- mice were remarkably reversed,
including ROS, COX-2 expression, lung inflammation, and Th2/Th17 cytokines.
Importantly, plasma miR-155 levels were elevated in severe asthmatics when
compared with nonasthmatics or mild-to-moderate asthmatics. These increased
plasma miR-155 levels were also observed in asthmatics with cockroach allergy
compared with those without cockroach allergy. Collectively, these findings
suggest that COX-2 is a major gene related to cockroach allergen-induced
oxidative stress and highlight a novel role of miR-155 in regulating the ROS-COX
2 axis in asthma.
PMID- 29967103
TI - ORNL Advances 99Mo Production Technologies.
PMID- 29967102
TI - Erratum.
PMID- 29967104
TI - Annual Report: Cancer Mortality Continues Decline.
PMID- 29967105
TI - SNMMI Leadership Update: Trailblazing and Expanding Frontiers.
PMID- 29967108
TI - NIH AD Summit 2018 Yields Research Recommendations.
PMID- 29967109
TI - A unique model for SDH-deficient GIST: an endocrine-related cancer.
AB - We describe a unique patient-derived xenograft (PDX) and cell culture model of
succinate dehydrogenase-deficient gastrointestinal stromal tumor (SDH-deficient
GIST), a rare mesenchymal tumor that can occur in association with paragangliomas
in hereditary and non-hereditary syndromes. This model is potentially important
for what it might reveal specifically pertinent to this rare tumor type and, more
broadly, to other types of SDH-deficient tumors. The primary tumor and xenografts
show a very high proliferative fraction, and distinctive morphology characterized
by tiny cells with marked autophagic activity. It is likely that these
characteristics resulted from the combination of the germline SDHB mutation and a
somatic KRAS G12D mutation. The most broadly relevant findings to date concern
oxygen and oxidative stress. In paragangliomas harboring SDHx mutations, both
hypoxic signaling and oxidative stress are putative drivers of tumor growth.
However, there are no models for SDH-deficient paragangliomas. This related model
is the first from a SDHB-mutated human tumor that can be experimentally
manipulated to study mechanisms of oxygen effects and novel treatment strategies.
Our data suggest that tumor growth and survival require a balance between
protective effects of hypoxic signaling vs deleterious effects of oxidative
stress. While reduced oxygen concentration promotes tumor cell survival, a
further survival benefit is achieved with antioxidants. This suggests potential
use of drugs that increase oxidative stress as novel therapies. In addition,
autophagy, which has not been reported as a major finding in any type of SDH
deficient tumor, is a potential target of agents that might trigger autophagic
cell death.
PMID- 29967110
TI - Adaptive Resistance to EGFR-Targeted Therapy by Calcium Signaling in NSCLC Cells.
AB - Targeted therapies against oncogenic receptor tyrosine kinases (RTK) show
promising results in the clinic. Unfortunately, despite the initial positive
response, most patients develop therapeutic resistance. Most research has focused
on acquired resistance occurring after an extensive time of treatment; however,
the question remains as to how cells can survive an initial treatment, as early
resistance to apoptosis will enable cells to develop any growth-stimulating
mechanism. Here, the non-small cell lung cancer (NSCLC) PC9 cell line was used to
systematically profile, by mass spectrometry, changes in the proteome, kinome,
and phosphoproteome during early treatment with the EGFR inhibitor afatinib.
Regardless of the response, initial drug-sensitive cells rapidly adapt to
targeted therapy, and within days, cells regained the capacity to proliferate,
despite persisting target inhibition. These data reveal a rapid reactivation of
mTOR and MAPK signaling pathways after initial inhibition and an increase in
abundance and activity of cytoskeleton and calcium signaling-related proteins.
Pharmacologic inhibition of reactivated pathways resulted in increased afatinib
efficacy. However more strikingly, cells that were restricted from accessing
extracellular calcium were extremely sensitive to afatinib treatment. These
findings were validated using three additional inhibitors tested in four
different NSCLC cell lines, and the data clearly indicated a role for Ca2+
signaling during the development of adaptive resistance. From a therapeutic point
of view, the increased inhibitor efficacy could limit or even prevent further
resistance development.Implications: Combined targeting of calcium signaling and
RTKs may limit drug resistance and improve treatment efficacy. Mol Cancer Res;
16(11); 1773-84. (c)2018 AACR.
PMID- 29967112
TI - Literature Round-Up: Impactful Published Papers: Article Recommendations from Our
Deputy and Senior Editors.
PMID- 29967111
TI - CHP2 Promotes Cell Proliferation in Breast Cancer via Suppression of FOXO3a.
AB - Calcineurin B homologous protein isoform 2 (CHP2), an essential cofactor for
Na+/H+ exchanger isoform 1 (NHE1), is identified to be expressed in various
malignant cell lines. However, the clinical significance and biological role of
CHP2 in breast cancer remain to be established. Here, CHP2 was markedly
overexpressed in breast cancer cells and clinical tumor specimens.
Immunohistochemical analysis revealed that the expression of CHP2 was
significantly correlated with patients' clinicopathologic characteristics like
clinical stage, and breast cancer patients with high CHP2 expression had shorter
overall survival compared with patients with low CHP2 expression. Moreover, it
was demonstrated that overexpressing CHP2 significantly enhanced, whereas
silencing endogenous CHP2 inhibited, the proliferation and tumorigenicity of
breast cancer cells in vitro and in vivo In addition, overexpression of CHP2
accelerated, whereas inhibition of CHP2 retarded, G1-S phase cell-cycle
transition in breast cancer cells. Mechanistically, overexpression of CHP2
activated AKT signaling and suppressed the transactivation of the forkhead box O3
(FOXO3/FOXO3a) transcription factor.Implications: This study discovers a
previously unrecognized role of CHP2 in the progression of breast cancer and
supports the significance of this gene as a novel prognostic biomarker and a
potential therapeutic target for breast cancer. Mol Cancer Res; 16(10); 1512-22.
(c)2018 AACR.
PMID- 29967113
TI - The Sixth Annual AACR-CRI Lloyd J. Old Award in Cancer Immunology.
PMID- 29967114
TI - GMC hearings: Does not attending mean I'm more likely to be struck off?
PMID- 29967115
TI - Margaret McCartney: Should doctors go to patients' funerals?
PMID- 29967116
TI - Identification and biochemical characterization of a novel PP2C-like Ser/Thr
phosphatase in E. coli.
AB - In bacteria, signaling phosphorylation is thought to occur primarily on His and
Asp residues. However, phosphoproteomic surveys in phylogenetically diverse
bacteria over the past decade have identified numerous proteins that are
phosphorylated on Ser and/or Thr residues. Consistently, genes encoding Ser/Thr
kinases are present in many bacterial genomes such as E. coli, which encodes at
least three Ser/Thr kinases. Since Ser/Thr phosphorylation is a stable
modification, a dedicated phosphatase is necessary to allow reversible
regulation. Ser/Thr phosphatases belonging to several conserved families are
found in bacteria. One family of particular interest are Ser/Thr phosphatases
which have extensive sequence and structural homology to eukaryotic Ser/Thr PP2C
phosphatases. These proteins, called eSTPs (eukaryotic-like Ser/Thr
phosphatases), have been identified in a number of bacteria, but not in E. coli
Here, we describe a previously unknown eSTP encoded by an E. coli ORF, yegK, and
characterize its biochemical properties including its kinetics, substrate
specificity and sensitivity to known phosphatase inhibitors. We investigate
differences in the activity of this protein in closely related E. coli strains.
Finally, we demonstrate that this eSTP acts to dephosphorylate a novel Ser/Thr
kinase which is encoded in the same operon.Importance Regulatory protein
phosphorylation is a conserved mechanism of signaling in all biological systems.
Recent phosphoproteomic analyses of phylogenetically diverse bacteria including
the model Gram-negative bacterium E. coli demonstrate that many proteins are
phosphorylated on serine or threonine residues. In contrast to phosphorylation on
histidine or aspartate residues, phosphorylation of serine and threonine residues
is stable and requires the action of a partner Ser/Thr phosphatase to remove the
modification. Although a number of Ser/Thr kinases have been reported in E. coli,
no partner Ser/Thr phosphatases have been identified. Here, we biochemically
characterize a novel Ser/Thr phosphatase that acts to dephosphorylate a Ser/Thr
kinase that is encoded in the same operon.
PMID- 29967117
TI - Repression of Capsule Production by XdrA and CodY in Staphylococcus aureus.
AB - Capsule is one of many virulence factors produced by Staphylococcus aureus, and
its expression is highly regulated. Here, we report the repression of capsule by
direct interaction of XdrA and CodY with the capsule promoter region. We found,
by footprinting analyses, that XdrA repressed capsule by binding to a broad
region that extended from upstream of the -35 region of the promoter to the
coding region of capA, the first gene of the 16-gene cap operon. Footprinting
analyses also revealed that CodY bound to a large region that overlapped
extensively with that of XdrA. We found that repression of the cap genes in the
xdrA mutant could be achieved by the overexpression of codY but not vice versa,
suggesting codY is epistatic to xdrA However, we found XdrA had no effect on CodY
expression. These results suggest that XdrA plays a secondary role in capsule
regulation by promoting CodY repression of the cap genes. Oxacillin slightly
induced xdrA expression and reduced cap promoter activity, but the effect of
oxacillin on capsule was not mediated through XdrA.IMPORTANCEStaphylococcus
aureus employs a complex regulatory network to coordinate the expression of
various virulence genes to achieve successful infections. How virulence genes are
coordinately regulated is still poorly understood. We have been studying capsule
regulation as a model system to explore regulatory networking in S. aureus In
this study, we found that XdrA and CodY have broad binding sites that overlap
extensively in the capsule promoter region. Our results also suggest that XdrA
assists CodY in the repression of capsule. As capsule gene regulation by DNA
binding regulators has not been fully investigated, the results presented here
fill an important knowledge gap, thereby further advancing our understanding of
the global virulence regulatory network in S. aureus.
PMID- 29967118
TI - Characterization of Three Small Proteins in Brucella abortus Linked to Fucose
Utilization.
AB - Elucidating the function of proteins <50 amino acids in length is no small task.
Nevertheless, small proteins can play vital roles in the lifestyle of bacteria
and influence the virulence of pathogens; thus, the investigation of the small
proteome is warranted. Recently, our group identified the Brucella abortus
protein VtlR as a transcriptional activator of four genes, one of which is the
well-studied small regulatory RNA AbcR2, while the other three genes encode
hypothetical small proteins, two of which are highly conserved among the order
Rhizobiales This study provides evidence that all three genes encode authentic
small proteins and that all three are highly expressed under oxidative stress,
low-pH, and stationary-phase growth conditions. Fractionation of the cells
revealed that the proteins are localized to the membranes of B. abortus We
demonstrate that the small proteins under the transcriptional control of VtlR are
not accountable for attenuation observed with the B. abortusvtlR deletion strain.
However, there is an association between VtlR-regulated genes and growth
inhibition in the presence of the sugar l-fucose. Subsequent transcriptomic
analyses revealed that B. abortus initiates the transcription of a locus encoding
a putative sugar transport and utilization system when the bacteria are cultured
in the presence of l-fucose. Altogether, our observations characterize the role
of the VtlR-controlled small proteins BAB1_0914, BAB2_0512, and BAB2_0574 in the
biology of B. abortus, particularly in the capacity of the bacteria to utilize l
fucose.IMPORTANCE Despite being one of the most common zoonoses worldwide, there
is currently no human vaccine to combat brucellosis. Therefore, a better
understanding of the pathogenesis and biology of Brucella spp., the causative
agent of brucellosis, is essential for the discovery of novel therapeutics
against these highly infectious bacteria. In this study, we further characterize
the virulence-associated transcriptional regulator VtlR in Brucella abortus Our
findings not only shed light on our current understanding of a virulence related
genetic system in Brucella spp. but also increase our knowledge of small proteins
in the field of bacteriology.
PMID- 29967120
TI - Magnesium Suppresses Defects in the Formation of 70S Ribosomes as Well as in
Sporulation Caused by Lack of Several Individual Ribosomal Proteins.
AB - Individually, the ribosomal proteins L1, L23, L36, and S6 are not essential for
cell proliferation of Bacillus subtilis, but the absence of any one of these
ribosomal proteins causes a defect in the formation of the 70S ribosomes and a
reduced growth rate. In mutant strains individually lacking these ribosomal
proteins, the cellular Mg2+ content was significantly reduced. The deletion of
YhdP, an exporter of Mg2+, and overexpression of MgtE, the main importer of Mg2+,
increased the cellular Mg2+ content and restored the formation of 70S ribosomes
in these mutants. The increase in the cellular Mg2+ content improved the growth
rate and the cellular translational activity of the DeltarplA (L1) and the
DeltarplW (L23) mutants but did not restore those of the DeltarpmJ (L36) and the
DeltarpsF (S6) mutants. The lack of L1 caused a decrease in the production of
Spo0A, the master regulator of sporulation, resulting in a decreased sporulation
frequency. However, deletion of yhdP and overexpression of mgtE increased the
production of Spo0A and partially restored the sporulation frequency in the
DeltarplA (L1) mutant. These results indicate that Mg2+ can partly complement the
function of several ribosomal proteins, probably by stabilizing the conformation
of the ribosome.IMPORTANCE We previously reported that an increase in cellular
Mg2+ content can suppress defects in 70S ribosome formation and growth rate
caused by the absence of ribosomal protein L34. In the present study, we
demonstrated that, even in mutants lacking individual ribosomal proteins other
than L34 (L1, L23, L36, and S6), an increase in the cellular Mg2+ content could
restore 70S ribosome formation. Moreover, the defect in sporulation caused by the
absence of L1 was also suppressed by an increase in the cellular Mg2+ content.
These findings indicate that at least part of the function of these ribosomal
proteins can be complemented by Mg2+, which is essential for all living cells.
PMID- 29967122
TI - An interview with Richard Gardner.
AB - Richard Gardner began his career as a PhD student with Bob Edwards and ran his
own lab, focusing on patterning of the early mammalian embryo, at the University
of Oxford from 1973 until his retirement in 2008. A Fellow of the Royal Society
since 1979, he was knighted for services to Biological Sciences in 2005 and
received an Honorary Doctorate from Cambridge University in 2012. This year he
was awarded the British Society of Developmental Biology (BSDB) Waddington Medal
for major contributions to developmental biology in the UK. We caught up with him
at the society's Spring Meeting in Warwick and discussed how a book of birds set
him on a path to science, how his research was complemented by decades of
advising government on scientific policy and why picking the right mentor in
research is so important.
PMID- 29967121
TI - Swarmer Cell Development of the Bacterium Proteus mirabilis Requires the
Conserved Enterobacterial Common Antigen Biosynthesis Gene rffG.
AB - Individual cells of the bacterium Proteus mirabilis can elongate up to 40-fold on
surfaces before engaging in a cooperative surface-based motility termed swarming.
How cells regulate this dramatic morphological remodeling remains an open
question. In this paper, we move forward the understanding of this regulation by
demonstrating that P. mirabilis requires the gene rffG for swarmer cell
elongation and subsequent swarm motility. The rffG gene encodes a protein
homologous to the dTDP-glucose 4,6-dehydratase protein of Escherichia coli, which
contributes to enterobacterial common antigen biosynthesis. Here, we characterize
the rffG gene in P. mirabilis, demonstrating that it is required for the
production of large lipopolysaccharide-linked moieties necessary for wild-type
cell envelope integrity. We show that the absence of the rffG gene induces
several stress response pathways, including those controlled by the
transcriptional regulators RpoS, CaiF, and RcsB. We further show that in rffG
deficient cells, the suppression of the Rcs phosphorelay, via loss of RcsB, is
sufficient to induce cell elongation and swarm motility. However, the loss of
RcsB does not rescue cell envelope integrity defects and instead results in
abnormally shaped cells, including cells producing more than two poles. We
conclude that an RcsB-mediated response acts to suppress the emergence of shape
defects in cell envelope-compromised cells, suggesting an additional role for
RcsB in maintaining cell morphology under stress conditions. We further propose
that the composition of the cell envelope acts as a checkpoint before cells
initiate swarmer cell elongation and motility.IMPORTANCEProteus mirabilis swarm
motility has been implicated in pathogenesis. We have found that cells deploy
multiple uncharacterized strategies to handle cell envelope stress beyond the Rcs
phosphorelay when attempting to engage in swarm motility. While RcsB is known to
directly inhibit the master transcriptional regulator for swarming, we have shown
an additional role for RcsB in protecting cell morphology. These data support a
growing appreciation that the Rcs phosphorelay is a multifunctional regulator of
cell morphology in addition to its role in microbial stress responses. These data
also strengthen the paradigm that outer membrane composition is a crucial
checkpoint for modulating entry into swarm motility. Furthermore, the rffG
dependent moieties provide a novel attractive target for potential
antimicrobials.
PMID- 29967119
TI - After the Fact(or): Posttranscriptional Gene Regulation in Enterohemorrhagic
Escherichia coli O157:H7.
AB - To adapt to ever-changing environments, pathogens quickly alter gene expression.
This can occur through transcriptional, posttranscriptional, or posttranslational
regulation. Historically, transcriptional regulation has been thoroughly studied
to understand pathogen niche adaptation, whereas posttranscriptional and
posttranslational gene regulation has only relatively recently been appreciated
to play a central role in bacterial pathogenesis. Posttranscriptional regulation
may involve chaperones, nucleases, and/or noncoding small RNAs (sRNAs) and
typically controls gene expression by altering the stability and/or translation
of the target mRNA. In this review, we highlight the global importance of
posttranscriptional regulation to enterohemorrhagic Escherichia coli (EHEC) gene
expression and discuss specific mechanisms of how EHEC regulates expression of
virulence factors critical to host colonization and disease progression. The low
infectious dose of this intestinal pathogen suggests that EHEC is particularly
well adapted to respond to the host environment.
PMID- 29967123
TI - Two independent sulfation processes regulate mouth-form plasticity in the
nematode Pristionchus pacificus.
AB - Sulfation of biomolecules, like phosphorylation, is one of the most fundamental
and ubiquitous biochemical modifications with important functions during
detoxification. This process is reversible, involving two enzyme classes: a
sulfotransferase, which adds a sulfo group to a substrate; and a sulfatase that
removes the sulfo group. However, unlike phosphorylation, the role of sulfation
in organismal development is poorly understood. In this study, we find that two
independent sulfation events regulate the development of mouth morphology in the
nematode Pristionchus pacificus. This nematode has the ability to form two
alternative mouth morphologies depending on environmental cues, an example of
phenotypic plasticity. We found that, in addition to a previously described
sulfatase, a sulfotransferase is involved in regulating the mouth-form dimorphism
in P. pacificus However, it is unlikely that both of these sulfation-associated
enzymes act upon the same substrates, as they are expressed in different cell
types. Furthermore, animals mutant in genes encoding both enzymes show condition
dependent epistatic interactions. Thus, our study highlights the role of
sulfation-associated enzymes in phenotypic plasticity of mouth structures in
Pristionchus.
PMID- 29967124
TI - Correction: Early bioelectric activities mediate redox-modulated regeneration
(doi: 10.1242/dev.142034).
PMID- 29967125
TI - Stratum recruits Rab8 at Golgi exit sites to regulate the basolateral sorting of
Notch and Sanpodo.
AB - In Drosophila, the sensory organ precursor (SOP or pI cell) divides
asymmetrically to give birth to daughter cells, the fates of which are governed
by the differential activation of the Notch pathway. Proteolytic activation of
Notch induced by ligand is based on the correct polarized sorting and
localization of the Notch ligand Delta, the Notch receptor and its trafficking
partner Sanpodo (Spdo). Here, we have identified Stratum (Strat), a presumptive
guanine nucleotide exchange factor for Rab GTPases, as a regulator of Notch
activation. Loss of Strat causes cell fate transformations associated with an
accumulation of Notch, Delta and Spdo in the trans-Golgi network (TGN), and an
apical accumulation of Spdo. The strat mutant phenotype is rescued by the
catalytically active as well as the wild-type form of Rab8, suggesting a
chaperone function for Strat rather than that of exchange factor. Strat is
required to localize Rab8 at the TGN, and rab8 phenocopies strat We propose that
Strat and Rab8 act at the exit of the Golgi apparatus to regulate the sorting and
the polarized distribution of Notch, Delta and Spdo.
PMID- 29967126
TI - Corrigendum: SQANTI: extensive characterization of long-read transcript sequences
for quality control in full-length transcriptome identification and
quantification.
PMID- 29967127
TI - Cold acclimation conditions constrain plastic responses for resistance to cold
and starvation in Drosophila immigrans.
AB - In montane Drosophila species, cold-induced plastic changes in energy metabolites
are likely developed to cope with cold and starvation stress. Adult Drosophila
immigrans reared at 15 degrees C were acclimated at 0 degrees C or 7 degrees C
for durations of up to 6 days (fed or unfed conditions). Such flies were tested
for plastic changes in resistance to cold or starvation stress as well as for
possible accumulation and utilization of four energy metabolites (body lipids,
proline, trehalose and glycogen). Adults acclimated at 7 degrees C revealed a
greater increase in cold tolerance than flies acclimated at 0 degrees C.
Different durations of cold acclimation at 7 degrees C led to increased level of
body lipids only in fed flies which were utilized under starvation stress.
However, such plastic responses were not observed in the flies acclimated at 0
degrees C, which remained unfed due to chill-coma. These observations suggest a
possible role of feeding to improve starvation resistance only in the flies
acclimated at 7 degrees C with food. Cold acclimated D. immigrans flies revealed
improved cold resistance through a possible reshuffling of trehalose and
glycogen; and starvation-induced proline which was utilized under cold stress
durations. Finally, greater reduction in mean daily fecundity due to cold or
starvation was observed in 0 degrees C acclimated flies as compared to 7 degrees
C acclimated flies. Thus, cold acclimation conditions (0 degrees C or 7 degrees
C) greatly impact resistance to cold and starvation in D. immigrans.
PMID- 29967128
TI - Extracellular vesicles in DLBCL provide abundant clues to aberrant
transcriptional programming and genomic alterations.
AB - The biological role of extracellular vesicles (EVs) in diffuse large B-cell
lymphoma (DLBCL) initiation and progression remains largely unknown. We
characterized EVs secreted by 5 DLBCL cell lines, a primary DLBCL tumor, and a
normal control B-cell sample, optimized their purification, and analyzed their
content. We found that DLBCLs secreted large quantities of CD63, Alix, TSG101,
and CD81 EVs, which can be extracted using an ultracentrifugation-based method
and traced by their cell of origin surface markers. We also showed that tumor
derived EVs can be exchanged between lymphoma cells, normal tonsillar cells, and
HK stromal cells. We then examined the content of EVs, focusing on isolation of
high-quality total RNA. We sequenced the total RNA and analyzed the nature of RNA
species, including coding and noncoding RNAs. We compared whole-cell and EV
derived RNA composition in benign and malignant B cells and discovered that
transcripts from EVs were involved in many critical cellular functions. Finally,
we performed mutational analysis and found that mutations detected in EVs
exquisitely represented mutations in the cell of origin. These results enhance
our understanding and enable future studies of the role that EVs may play in the
pathogenesis of DLBCL, particularly with regards to the exchange of genomic
information. Current findings open a new strategy for liquid biopsy approaches in
disease monitoring.
PMID- 29967130
TI - How I treat the young patient with multiple myeloma.
AB - The treatment landscape for multiple myeloma has been transformed by the
introduction of novel agents, including immunomodulatory drugs, proteasome
inhibitors, and monoclonal antibodies. These have been shown to be more effective
and generally better tolerated than conventional chemotherapy, with their
introduction into clinical practice leading to improved survival. Furthermore, a
better understanding of disease biology, improved diagnostic criteria, and the
development of sensitive and specific tools for disease prognostication have
contributed to better outcome. Treatment in the younger patient can now be
individualized based on host and disease features with enhanced monitoring of
response and use of high-sensitivity techniques for evaluating residual disease.
The current standard of care has been significantly enhanced by novel agents with
a paradigm shift toward optional or delayed autologous stem cell transplant as a
reasonable choice in selected patients. Conversely, extended treatment with
induction of remission followed by maintenance strategies is now a standard of
care, conferring prolonged disease control with more manageable toxicities in
both the short and long term, as well as improved quality of life.
PMID- 29967129
TI - Integrative genomic analysis reveals cancer-associated mutations at diagnosis of
CML in patients with high-risk disease.
AB - Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are
poorly understood. We performed whole-exome sequencing, copy-number variation,
and/or RNA sequencing for 65 patients to discover mutations at diagnosis and
blast crisis (BC). Forty-six patients with chronic-phase disease with the
extremes of outcome were studied at diagnosis. Cancer gene variants were detected
in 15 (56%) of 27 patients with subsequent BC or poor outcome and in 3 (16%) of
19 optimal responders (P = .007). Frequently mutated genes at diagnosis were
ASXL1, IKZF1, and RUNX1 The methyltransferase SETD1B was a novel recurrently
mutated gene. A novel class of variant associated with the Philadelphia (Ph)
translocation was detected at diagnosis in 11 (24%) of 46 patients comprising
fusions and/or rearrangement of genes on the translocated chromosomes, with
evidence of fragmentation, inversion, and imperfect sequence reassembly. These
were more frequent at diagnosis in patients with poor outcome: 9 (33%) of 27 vs 2
(11%) of 19 optimal responders (P = .07). Thirty-nine patients were tested at BC,
and all had cancer gene variants, including ABL1 kinase domain mutations in 58%.
However, ABL1 mutations cooccurred with other mutated cancer genes in 89% of
cases, and these predated ABL1 mutations in 62% of evaluable patients. Gene
fusions not associated with the Ph translocation occurred in 42% of patients at
BC and commonly involved fusion partners that were known cancer genes (78%).
Genomic analysis revealed numerous relevant variants at diagnosis in patients
with poor outcome and all patients at BC. Future refined biomarker testing of
specific variants will likely provide prognostic information to facilitate a risk
adapted therapeutic approach.
PMID- 29967131
TI - Pulmonary renal syndrome in Henoch-Schonlein purpura.
PMID- 29967132
TI - Routine micturating cystourethrogram for multicystic dysplastic kidneys: have we
moved on?
PMID- 29967133
TI - Novel pathogenic SMAD2 variants in five families with arterial aneurysm and
dissection: further delineation of the phenotype.
AB - BACKGROUND: Missense variants in SMAD2, encoding a key transcriptional regulator
of transforming growth factor beta signalling, were recently reported to cause
arterial aneurysmal disease. OBJECTIVES: The aims of the study were to identify
the genetic disease cause in families with aortic/arterial aneurysmal disease and
to further define SMAD2 genotype-phenotype correlations. METHODS AND RESULTS:
Using gene panel sequencing, we identified a SMAD2 nonsense variant and four
SMAD2 missense variants, all affecting highly conserved amino acids in the MH2
domain. The premature stop codon (c.612dup; p.(Asn205*)) was identified in a
marfanoid patient with aortic root dilatation and in his affected father. A
p.(Asn318Lys) missense variant was found in a Marfan syndrome (MFS)-like case who
presented with aortic root aneurysm and in her affected daughter with marfanoid
features and mild aortic dilatation. In a man clinically diagnosed with Loeys
Dietz syndrome (LDS) that presents with aortic root dilatation and marked
tortuosity of the neck vessels, another missense variant, p.(Ser397Tyr), was
identified. This variant was also found in his affected daughter with
hypertelorism and arterial tortuosity, as well as his affected mother. The third
missense variant, p.(Asn361Thr), was discovered in a man presenting with coronary
artery dissection. Variant genotyping in three unaffected family members
confirmed its absence. The last missense variant, p.(Ser467Leu), was identified
in a man with significant cardiovascular and connective tissue involvement.
CONCLUSION: Taken together, our data suggest that heterozygous loss-of-function
SMAD2 variants can cause a wide spectrum of autosomal dominant aortic and
arterial aneurysmal disease, combined with connective tissue findings reminiscent
of MFS and LDS.
PMID- 29967134
TI - Upregulated immune checkpoint HHLA2 in clear cell renal cell carcinoma: a novel
prognostic biomarker and potential therapeutic target.
AB - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a malignant urogenital
cancer with high mortality; however, current progress in understanding its
molecular mechanism and predicting clinical treatment outcome is limited.
Therefore, this study is to evaluate the clinical significance of immune
inhibitory molecular human endogenous retrovirus-H long terminal repeat
associating protein 2 (HHLA2) in ccRCC prognosis and transcriptional regulatory
network. METHODS: Expression of HHLA2 in ccRCC was examined by an online database
platform ONCOMINE. The ONCOMINE result was independently validated by qRT-PCR and
immunohistochemistry. Kaplan-Meier survival was generated using IBM SPSS
Statistics V.22. ccRCC tissues cells with high HHLA2 were sorted and subjected to
microarray transcriptional profiling and analysis. RESULTS: It was shown that
expression of HHLA2 was statistically significantly increased in ccRCC tissues
compared with normal renal tissues at both transcriptional and protein level.
Moreover, the expression of HHLA2 was closely correlated with multiple
clinicopathological features including tumour size, clinical stage and
histological grade. High HHLA2 expression was associated with poor overall
survival and clinical outcome. Comprehensive microarray analysis further
identified thousands of HHLA2 targets including mRNA, long non-coding RNA and
circular RNA that might function in various biological processes, especially,
immune response. CONCLUSION: Increased HHLA2 expression was observed in ccRCC
tumour tissue, which leads to a remarkable shorter overall survival and poorer
prognosis. Together with other molecular evidence, we have demonstrated that
HHLA2 could be a potential prognostic biomarker for ccRCC.
PMID- 29967135
TI - Folding artificial mucosa with cell-laden hydrogels guided by mechanics models.
AB - The surfaces of many hollow or tubular tissues/organs in our respiratory,
gastrointestinal, and urogenital tracts are covered by mucosa with folded
patterns. The patterns are induced by mechanical instability of the mucosa under
compression due to constrained growth. Recapitulating this folding process in
vitro will facilitate the understanding and engineering of mucosa in various
tissues/organs. However, scant attention has been paid to address the challenge
of reproducing mucosal folding. Here we mimic the mucosal folding process using a
cell-laden hydrogel film attached to a prestretched tough-hydrogel substrate. The
cell-laden hydrogel constitutes a human epithelial cell lining on stromal
component to recapitulate the physiological feature of a mucosa. Relaxation of
the prestretched tough-hydrogel substrate applies compressive strains on the cell
laden hydrogel film, which undergoes mechanical instability and evolves into
morphological patterns. We predict the conditions for mucosal folding as well as
the morphology of and strain in the folded artificial mucosa using a combination
of theory and simulation. The work not only provides a simple method to fold
artificial mucosa but also demonstrates a paradigm in tissue engineering via
harnessing mechanical instabilities guided by quantitative mechanics models.
PMID- 29967136
TI - Sinking particles promote vertical connectivity in the ocean microbiome.
AB - The sinking of organic particles formed in the photic layer is a main vector of
carbon export into the deep ocean. Although sinking particles are heavily
colonized by microbes, so far it has not been explored whether this process plays
a role in transferring prokaryotic diversity from surface to deep oceanic layers.
Using Illumina sequencing of the 16S rRNA gene, we explore here the vertical
connectivity of the ocean microbiome by characterizing marine prokaryotic
communities associated with five different size fractions and examining their
compositional variability from surface down to 4,000 m across eight stations
sampled in the Atlantic, Pacific, and Indian Oceans during the Malaspina 2010
Expedition. Our results show that the most abundant prokaryotes in the deep ocean
are also present in surface waters. This vertical community connectivity seems to
occur predominantly through the largest particles because communities in the
largest size fractions showed the highest taxonomic similarity throughout the
water column, whereas free-living communities were more isolated vertically. Our
results further suggest that particle colonization processes occurring in surface
waters determine to some extent the composition and biogeography of bathypelagic
communities. Overall, we postulate that sinking particles function as vectors
that inoculate viable particle-attached surface microbes into the deep-sea realm,
determining to a considerable extent the structure, functioning, and biogeography
of deep ocean communities.
PMID- 29967137
TI - Synthetic far-red light-mediated CRISPR-dCas9 device for inducing functional
neuronal differentiation.
AB - The ability to control the activity of CRISPR-dCas9 with precise spatiotemporal
resolution will enable tight genome regulation of user-defined endogenous genes
for studying the dynamics of transcriptional regulation. Optogenetic devices with
minimal phototoxicity and the capacity for deep tissue penetration are extremely
useful for precise spatiotemporal control of cellular behavior and for future
clinic translational research. Therefore, capitalizing on synthetic biology and
optogenetic design principles, we engineered a far-red light (FRL)-activated
CRISPR-dCas9 effector (FACE) device that induces transcription of exogenous or
endogenous genes in the presence of FRL stimulation. This versatile system
provides a robust and convenient method for precise spatiotemporal control of
endogenous gene expression and also has been demonstrated to mediate targeted
epigenetic modulation, which can be utilized to efficiently promote
differentiation of induced pluripotent stem cells into functional neurons by up
regulating a single neural transcription factor, NEUROG2 This FACE system might
facilitate genetic/epigenetic reprogramming in basic biological research and
regenerative medicine for future biomedical applications.
PMID- 29967138
TI - Vulnerability of Arctic marine mammals to vessel traffic in the increasingly ice
free Northwest Passage and Northern Sea Route.
AB - The fabled Northwest Passage and Northern Sea Route that were once the quests of
early Western explorers are now increasingly sea ice-free, with routine vessel
transits expected by midcentury. The potential impacts of this novel vessel
traffic on endemic Arctic marine mammal (AMM) species are unknown despite their
critical social and ecological roles in the ecosystem and widely recognized
susceptibility to ice loss. We developed a vulnerability assessment of 80
subpopulations of seven AMM species to vessel traffic during the ice-free season.
Vulnerability scores were based on the combined influence of spatially explicit
exposure to the sea routes and a suite of sensitivity variables. More than half
of AMM subpopulations (42/80) are exposed to open-water vessel transits in the
Arctic sea routes. Narwhals (Monodon monoceros) were estimated to be most
vulnerable to vessel impacts, given their high exposure and sensitivity, and
polar bears (Ursus maritimus) were estimated to be the least vulnerable because
of their low exposure and sensitivity. Regions with geographic bottlenecks, such
as the Bering Strait and eastern Canadian Arctic, were characterized by two to
three times higher vulnerability than more remote regions. These pinch points are
obligatory pathways for both vessels and migratory AMMs, and so represent
potentially high conflict areas but also opportunities for conservation-informed
planning. Some of the species and regions identified as least vulnerable were
also characterized by high uncertainty, highlighting additional data and
monitoring needs. Our quantification of the heterogeneity of risk across AMM
species provides a necessary first step toward developing best practices for
maritime industries poised to advance into this rapidly changing seascape.
PMID- 29967139
TI - Minor zygotic gene activation is essential for mouse preimplantation development.
AB - In mice, transcription initiates at the mid-one-cell stage and transcriptional
activity dramatically increases during the two-cell stage, a process called
zygotic gene activation (ZGA). Associated with ZGA is a marked change in the
pattern of gene expression that occurs after the second round of DNA replication.
To distinguish ZGA before and after the second-round DNA replication, the former
and latter are called minor and major ZGA, respectively. Although major ZGA are
required for development beyond the two-cell stage, the function of minor ZGA is
not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-beta-d
ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting
at the two-cell stage and retention of the H3K4me3 mark that normally decreases.
After release from DRB, at which time major ZGA normally occurred, transcription
initiated with characteristics of minor ZGA but not major ZGA, although
degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially
starting with minor ZGA that is critical for the maternal-to-zygotic transition.
PMID- 29967141
TI - US nuclear power: The vanishing low-carbon wedge.
AB - Nuclear power holds the potential to make a significant contribution to
decarbonizing the US energy system. Whether it could do so in its current form is
a critical question: Existing large light water reactors in the United States are
under economic pressure from low natural gas prices, and some have already
closed. Moreover, because of their great cost and complexity, it appears most
unlikely that any new large plants will be built over the next several decades.
While advanced reactor designs are sometimes held up as a potential solution to
nuclear power's challenges, our assessment of the advanced fission enterprise
suggests that no US design will be commercialized before midcentury. That leaves
factory-manufactured, light water small modular reactors (SMRs) as the only
option that might be deployed at significant scale in the climate-critical period
of the next several decades. We have systematically investigated how a domestic
market could develop to support that industry over the next several decades and,
in the absence of a dramatic change in the policy environment, have been unable
to make a convincing case. Achieving deep decarbonization of the energy system
will require a portfolio of every available technology and strategy we can
muster. It should be a source of profound concern for all who care about climate
change that, for entirely predictable and resolvable reasons, the United States
appears set to virtually lose nuclear power, and thus a wedge of reliable and low
carbon energy, over the next few decades.
PMID- 29967140
TI - Lifelong CMV infection improves immune defense in old mice by broadening the
mobilized TCR repertoire against third-party infection.
AB - Lifelong interactions between host and the ubiquitous and persistent
cytomegalovirus (CMV) have been proposed to contribute to the age-related decline
in immunity. Prior work from us and others found some support for that idea, yet
evidence that this led to increased vulnerability to other infections was not
obtained. Moreover, evidence has accumulated that CMV infection can be beneficial
to immune defense in young/adult mice and humans, dominantly via enhanced innate
immunity. Here, we describe an unexpected impact of murine CMV (MCMV) upon the T
cell response of old mice to Listeria monocytogenes expressing the model antigen,
OVA (Lm-OVA). Single-cell sequencing of the OVA-specific CD8 T cell receptor beta
(TCRbeta) repertoire of old mice demonstrated that old MCMV-infected mice
recruited many diverse clonotypes that afforded broad and often more efficient
recognition of antigenic peptide variants. This stood in contrast to old control
mice, which exhibited strong narrowing and homogenization of the elicited
repertoire. High-throughput sequencing of the total naive CD8 TCRbeta repertoire
showed that many of these diverse OVA-specific clonotypes were present in the
naive CD8 repertoire of mice in all groups (adult, old control, and old MCMV+)
yet were only recruited into the Lm-OVA response in MCMV+ old mice. These results
have profound implications for our understanding of T cell immunity over a life
span and suggest that our coevolution with CMV may include surprising,
potentially positive impacts on adaptive heterologous immunity in late life.
PMID- 29967142
TI - Human impact on the diversity and virulence of the ubiquitous zoonotic parasite
Toxoplasma gondii.
AB - A majority of emerging infectious diseases in humans are zoonoses. Understanding
factors that influence the emergence and transmission of zoonoses is pivotal for
their prevention and control. Toxoplasma gondii is one of the most widespread
zoonotic pathogens known today. Whereas only a few genotypes of T. gondii
dominate in the Northern Hemisphere, many genotypes coexist in South America.
Furthermore, T. gondii strains from South America are more likely to be virulent
than those from the Northern Hemisphere. However, it is not clear what factor(s)
shaped modern-day genetic diversity and virulence of T. gondii Here, our analysis
suggests that the rise and expansion of farming in the past 11,000 years
established the domestic cat/mouse transmission cycle for T. gondii, which has
undoubtedly played a significant role in the selection of certain linages of T.
gondii Our mathematical simulations showed that within the domestic transmission
cycle, intermediately mouse-virulent T. gondii genotypes have an adaptive
advantage and eventually become dominant due to a balance between lower host
mortality and the ability to superinfect mice previously infected with a less
virulent T. gondii strain. Our analysis of the global type II lineage of T.
gondii suggests its Old World origin but recent expansion in North America, which
is likely the consequence of global human migration and trading. These results
have significant implications concerning transmission and evolution of zoonotic
pathogens in the rapidly expanding anthropized environment demanded by rapid
growth of the human population and intensive international trading at present and
in the future.
PMID- 29967143
TI - Confinement generates single-crystal aragonite rods at room temperature.
AB - The topic of calcite and aragonite polymorphism attracts enormous interest from
fields including biomineralization and paleogeochemistry. While aragonite is only
slightly less thermodynamically stable than calcite under ambient conditions, it
typically only forms as a minor product in additive-free solutions at room
temperature. However, aragonite is an abundant biomineral, and certain organisms
can selectively generate calcite and aragonite. This fascinating behavior has
been the focus of decades of research, where this has been driven by a search for
specific organic macromolecules that can generate these polymorphs. However,
despite these efforts, we still have a poor understanding of how organisms
achieve such selectivity. In this work, we consider an alternative possibility
and explore whether the confined volumes in which all biomineralization occurs
could also influence polymorph. Calcium carbonate was precipitated within the
cylindrical pores of track-etched membranes, where these enabled us to
systematically investigate the relationship between the membrane pore diameter
and polymorph formation. Aragonite was obtained in increasing quantities as the
pore size was reduced, such that oriented single crystals of aragonite were the
sole product from additive-free solutions in 25-nm pores and significant
quantities of aragonite formed in pores as large as 200 nm in the presence of low
concentrations of magnesium and sulfate ions. This effect can be attributed to
the effect of the pore size on the ion distribution, which becomes of increasing
importance in small pores. These intriguing results suggest that organisms may
exploit confinement effects to gain control over crystal polymorph.
PMID- 29967144
TI - Past role and future outlook of the Conservation Reserve Program for supporting
honey bees in the Great Plains.
AB - Human dependence on insect pollinators continues to grow even as pollinators face
global declines. The Northern Great Plains (NGP), a region often referred to as
America's last honey bee (Apis mellifera) refuge, has undergone rapid land-cover
change due to cropland expansion and weakened land conservation programs. We
conducted a trend analysis and estimated conversion rates of Conservation Reserve
Program (CRP) enrollments around bee apiaries from 2006 to 2016 and developed
models to identify areas of habitat loss. Our analysis revealed that NGP apiaries
lost over 53% of lands enrolled in the CRP, and the rate of loss was highest in
areas of high apiary density. We estimated over 163,000 ha of CRP lands in 2006
within 1.6 km of apiaries was converted to row crops by 2012. We also evaluated
how alternative scenarios of future CRP acreage caps may affect habitat
suitability for supporting honey bee colonies. Our scenario revealed that a
further reduction in CRP lands to 7.7 million ha nationally would reduce the
number of apiaries in the NGP that meet defined forage criteria by 28% on
average. Alternatively, increasing the national cap to 15 million ha would
increase the number of NGP apiaries that meet defined forage criteria by 155%.
Our scenarios also show that strategic placement of CRP lands near existing
apiaries increased the number of apiaries that meet forage criteria by 182%. Our
research will be useful for informing the potential consequences of future US
farm bill policy and land management in the epicenter of the US beekeeping
industry.
PMID- 29967146
TI - QnAs with Shaul Mukamel.
PMID- 29967145
TI - Zyxin promotes colon cancer tumorigenesis in a mitotic phosphorylation-dependent
manner and through CDK8-mediated YAP activation.
AB - Zyxin is a member of the focal adhesion complex and plays a critical role in
actin filament polymerization and cell motility. Several recent studies showed
that Zyxin is a positive regulator of Yki/YAP (Yes-associated protein) signaling.
However, little is known about the mechanisms by which Zyxin itself is regulated
and how Zyxin affects Hippo-YAP activity. We first showed that Zyxin is
phosphorylated by CDK1 during mitosis. Depletion of Zyxin resulted in
significantly impaired colon cancer cell proliferation, migration, anchorage
independent growth, and tumor formation in xenograft animal models. Mitotic
phosphorylation is required for Zyxin activity in promoting growth. Zyxin
regulates YAP activity through the colon cancer oncogene CDK8. CDK8 knockout
phenocopied Zyxin knockdown in colon cancer cells, while ectopic expression of
CDK8 substantially restored the tumorigenic defects of Zyxin-depletion cells.
Mechanistically, we showed that CDK8 directly phosphorylated YAP and promoted its
activation. Fully activated YAP is required to support the growth in CDK8
knockout colon cancer cells in vitro and in vivo. Together, these observations
suggest that Zyxin promotes colon cancer tumorigenesis in a mitotic
phosphorylation-dependent manner and through CDK8-mediated YAP activation.
PMID- 29967147
TI - Feasting and the evolution of cooperative social organizations circa 2300 B.P. in
Paracas culture, southern Peru.
AB - Recent theoretical innovations in cultural evolutionary theory emphasize the role
of cooperative social organizations that unite diverse groups as a key step in
the evolution of social complexity. A principal mechanism identified by this
theory is feasting, a strategy that reinforces norms of cooperation. Feasts occur
throughout the premodern world, and the intensification of feasting is
empirically correlated to increased social complexity. A critical factor in
assessing the evolutionary significance of this practice is the scale and range
of the feast from that focused on a single community to ones that draw from a
large region or catchment zone. This work addresses the degree to which hosts
draw on a local area vs. a regional one in initial prehistoric feasting. We
report on excavations at a locus of intensive feasting-a ceremonial sunken court
in a fifth- to third-century BCE Paracas site on the south coast of Peru. We
selected 39 organic objects from the court placed as offerings during major
feasting episodes. We analyzed the radiogenic strontium isotope (87Sr/86Sr)
values to determine the geographical origin of each object. The 87Sr/86Sr data
plus additional archaeological data support a hypothesis that the catchment of
the court was quite extensive. The initial strategy of political and economic
alliance building was macroregional in scope. These data indicate that the most
effective initial strategy in early state formation in this case study was to
build wide alliances at the outset, as opposed to first consolidating local ones
that subsequently expand.
PMID- 29967148
TI - Plant height and hydraulic vulnerability to drought and cold.
AB - Understanding how plants survive drought and cold is increasingly important as
plants worldwide experience dieback with drought in moist places and grow taller
with warming in cold ones. Crucial in plant climate adaptation are the diameters
of water-transporting conduits. Sampling 537 species across climate zones
dominated by angiosperms, we find that plant size is unambiguously the main
driver of conduit diameter variation. And because taller plants have wider
conduits, and wider conduits within species are more vulnerable to conduction
blocking embolisms, taller conspecifics should be more vulnerable than shorter
ones, a prediction we confirm with a plantation experiment. As a result, maximum
plant size should be short under drought and cold, which cause embolism, or
increase if these pressures relax. That conduit diameter and embolism
vulnerability are inseparably related to plant size helps explain why factors
that interact with conduit diameter, such as drought or warming, are altering
plant heights worldwide.
PMID- 29967149
TI - Adaptation aftereffects reveal representations for encoding of contingent social
actions.
AB - A hallmark of human social behavior is the effortless ability to relate one's own
actions to that of the interaction partner, e.g., when stretching out one's arms
to catch a tripping child. What are the behavioral properties of the neural
substrates that support this indispensable human skill? Here we examined the
processes underlying the ability to relate actions to each other, namely the
recognition of spatiotemporal contingencies between actions (e.g., a "giving"
that is followed by a "taking"). We used a behavioral adaptation paradigm to
examine the response properties of perceptual mechanisms at a behavioral level.
In contrast to the common view that action-sensitive units are primarily
selective for one action (i.e., primary action, e.g., 'throwing"), we demonstrate
that these processes also exhibit sensitivity to a matching contingent action
(e.g., "catching"). Control experiments demonstrate that the sensitivity of
action recognition processes to contingent actions cannot be explained by lower
level visual features or amodal semantic adaptation. Moreover, we show that
action recognition processes are sensitive only to contingent actions, but not to
noncontingent actions, demonstrating their selective sensitivity to contingent
actions. Our findings show the selective coding mechanism for action
contingencies by action-sensitive processes and demonstrate how the
representations of individual actions in social interactions can be linked in a
unified representation.
PMID- 29967150
TI - Distinct ways of G:U recognition by conserved tRNA binding motifs.
AB - Throughout three domains of life, alanyl-tRNA synthetases (AlaRSs) recognize a
G3:U70 base pair in the acceptor stem of tRNAAla as the major identity
determinant of tRNAAla The crystal structure of the archaeon Archaeoglobus
fulgidus AlaRS in complex with tRNAAla provided the basis for G3:U70 recognition
with residues (Asp and Asn) that are conserved in the three domains [Naganuma M,
et al. (2014) Nature 510:507-511]. The recognition mode is unprecedented, with
specific accommodation of the dyad asymmetry of the G:U wobble pair and exclusion
of the dyad symmetry of a Watson-Crick pair. With this conserved mode,
specificity is based more on "fit" than on direct recognition of specific atomic
groups. Here, we show that, in contrast to the archaeal complex, the Escherichia
coli enzyme uses direct positive (energetically favorable) minor groove
recognition of the unpaired 2-amino of G3 by Asp and repulsion of a competing
base pair by Asn. Strikingly, mutations that disrupted positive recognition by
the E. coli enzyme had little or no effect on G:U recognition by the human
enzyme. Alternatively, Homo sapiens AlaRS selects G:U without positive
recognition and uses Asp instead to repel a competitor. Thus, the widely
conserved Asp-plus-Asn architecture of AlaRSs can select G:U in a straightforward
(bacteria) or two different unconventional (eukarya/archaea) ways. The adoption
of different modes for recognition of a widely conserved G:U pair in alanine
tRNAs suggests an early and insistent role for G:U in the development of the
genetic code.
PMID- 29967151
TI - Repurposing isoxazoline veterinary drugs for control of vector-borne human
diseases.
AB - Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite
control in companion animals. Here we propose their use in humans for the
reduction of vector-borne disease incidence. Fluralaner and afoxolaner rapidly
killed Anopheles, Aedes, and Culex mosquitoes and Phlebotomus sand flies after
feeding on a drug-supplemented blood meal, with IC50 values ranging from 33 to
575 nM, and were fully active against strains with preexisting resistance to
common insecticides. Based on allometric scaling of preclinical pharmacokinetics
data, we predict that a single human median dose of 260 mg (IQR, 177-407 mg) for
afoxolaner, or 410 mg (IQR, 278-648 mg) for fluralaner, could provide an
insecticidal effect lasting 50-90 days against mosquitoes and Phlebotomus sand
flies. Computational modeling showed that seasonal mass drug administration of
such a single dose to a fraction of a regional population would dramatically
reduce clinical cases of Zika and malaria in endemic settings. Isoxazolines
therefore represent a promising new component of drug-based vector control.
PMID- 29967152
TI - Traceless synthesis of ceramides in living cells reveals saturation-dependent
apoptotic effects.
AB - Mammalian cells synthesize thousands of distinct lipids, yet the function of many
of these lipid species is unknown. Ceramides, a class of sphingolipid, are
implicated in several cell-signaling pathways but poor cell permeability and lack
of selectivity in endogenous synthesis pathways have hampered direct study of
their effects. Here we report a strategy that overcomes the inherent biological
limitations of ceramide delivery by chemoselectively ligating lipid precursors in
vivo to yield natural ceramides in a traceless manner. Using this method, we
uncovered the apoptotic effects of several ceramide species and observed
differences in their apoptotic activity based on acyl-chain saturation.
Additionally, we demonstrate spatiotemporally controlled ceramide synthesis in
live cells through photoinitiated lipid ligation. Our in situ lipid ligation
approach addresses the long-standing problem of lipid-specific delivery and
enables the direct study of unique ceramide species in live cells.
PMID- 29967153
TI - Decoding on the ribosome depends on the structure of the mRNA phosphodiester
backbone.
AB - During translation, the ribosome plays an active role in ensuring that mRNA is
decoded accurately and rapidly. Recently, biochemical studies have also
implicated certain accessory factors in maintaining decoding accuracy. However,
it is currently unclear whether the mRNA itself plays an active role in the
process beyond its ability to base pair with the tRNA. Structural studies
revealed that the mRNA kinks at the interface of the P and A sites. A magnesium
ion appears to stabilize this structure through electrostatic interactions with
the phosphodiester backbone of the mRNA. Here we examined the role of the kink
structure on decoding using a well-defined in vitro translation system.
Disruption of the kink structure through site-specific phosphorothioate
modification resulted in an acute hyperaccurate phenotype. We measured rates of
peptidyl transfer for near-cognate tRNAs that were severely diminished and in
some instances were almost 100-fold slower than unmodified mRNAs. In contrast to
peptidyl transfer, the modifications had little effect on GTP hydrolysis by
elongation factor thermal unstable (EF-Tu), suggesting that only the proofreading
phase of tRNA selection depends critically on the kink structure. Although the
modifications appear to have no effect on typical cognate interactions, peptidyl
transfer for a tRNA that uses atypical base pairing is compromised. These
observations suggest that the kink structure is important for decoding in the
absence of Watson-Crick or G-U wobble base pairing at the third position. Our
findings provide evidence for a previously unappreciated role for the mRNA
backbone in ensuring uniform decoding of the genetic code.
PMID- 29967154
TI - Anthropogenic and biogenic CO2 fluxes in the Boston urban region.
AB - With the pending withdrawal of the United States from the Paris Climate Accord,
cities are now leading US actions toward reducing greenhouse gas emissions.
Implementing effective mitigation strategies requires the ability to measure and
track emissions over time and at various scales. We report CO2 emissions in the
Boston, MA, urban region from September 2013 to December 2014 based on
atmospheric observations in an inverse model framework. Continuous atmospheric
measurements of CO2 from five sites in and around Boston were combined with a
high-resolution bottom-up CO2 emission inventory and a Lagrangian particle
dispersion model to determine regional emissions. Our model-measurement framework
incorporates emissions estimates from submodels for both anthropogenic and
biological CO2 fluxes, and development of a CO2 concentration curtain at the
boundary of the study region based on a combination of tower measurements and
modeled vertical concentration gradients. We demonstrate that an emission
inventory with high spatial and temporal resolution and the inclusion of urban
biological fluxes are both essential to accurately modeling annual CO2 fluxes
using surface measurement networks. We calculated annual average emissions in the
Boston region of 0.92 kg C.m-2.y-1 (95% confidence interval: 0.79 to 1.06), which
is 14% higher than the Anthropogenic Carbon Emissions System inventory. Based on
the capability of the model-measurement approach demonstrated here, our framework
should be able to detect changes in CO2 emissions of greater than 18%, providing
stakeholders with critical information to assess mitigation efforts in Boston and
surrounding areas.
PMID- 29967155
TI - Conservation of mRNA quality control factor Ski7 and its diversification through
changes in alternative splicing and gene duplication.
AB - Eukaryotes maintain fidelity of gene expression by preferential degradation of
aberrant mRNAs that arise by errors in RNA processing reactions. In Saccharomyces
cerevisiae, Ski7 plays an important role in this mRNA quality control by
mediating mRNA degradation by the RNA exosome. Ski7 was initially thought to be
restricted to Saccharomyces cerevisiae and close relatives because the SKI7 gene
and its paralog HBS1 arose by whole genome duplication (WGD) in a recent
ancestor. We have recently shown that the preduplication gene was alternatively
spliced and that Ski7 function predates WGD. Here, we use transcriptome analysis
of diverse eukaryotes to show that diverse eukaryotes use alternative splicing of
SKI7/HBS1 to encode two proteins. Although alternative splicing affects the same
intrinsically disordered region of the protein, the pattern of splice site usage
varies. This alternative splicing event arose in an early eukaryote that is a
common ancestor of plants, animals, and fungi. Remarkably, through changes in
alternative splicing and gene duplication, the Ski7 protein has diversified such
that different species express one of four distinct Ski7-like proteins. We also
show experimentally that the Saccharomyces cerevisiae SKI7 gene has undergone
multiple changes that are incompatible with the Hbs1 function and may also have
undergone additional changes to optimize mRNA quality control. The combination of
transcriptome analysis in diverse eukaryotes and genetic analysis in yeast
clarifies the mechanism by which a Ski7-like protein is expressed across
eukaryotes and provides a unique view of changes in alternative splicing patterns
of one gene over long evolutionary time.
PMID- 29967156
TI - Ancient human parvovirus B19 in Eurasia reveals its long-term association with
humans.
AB - Human parvovirus B19 (B19V) is a ubiquitous human pathogen associated with a
number of conditions, such as fifth disease in children and arthritis and
arthralgias in adults. B19V is thought to evolve exceptionally rapidly among DNA
viruses, with substitution rates previously estimated to be closer to those
typical of RNA viruses. On the basis of genetic sequences up to ~70 years of age,
the most recent common ancestor of all B19V has been dated to the early 1800s,
and it has been suggested that genotype 1, the most common B19V genotype, only
started circulating in the 1960s. Here we present 10 genomes (63.9-99.7% genome
coverage) of B19V from dental and skeletal remains of individuals who lived in
Eurasia and Greenland from ~0.5 to ~6.9 thousand years ago (kya). In a
phylogenetic analysis, five of the ancient B19V sequences fall within or basal to
the modern genotype 1, and five fall basal to genotype 2, showing a long-term
association of B19V with humans. The most recent common ancestor of all B19V is
placed ~12.6 kya, and we find a substitution rate that is an order of magnitude
lower than inferred previously. Further, we are able to date the recombination
event between genotypes 1 and 3 that formed genotype 2 to ~5.0-6.8 kya. This
study emphasizes the importance of ancient viral sequences for our understanding
of virus evolution and phylogenetics.
PMID- 29967157
TI - Origins of equine dentistry.
AB - From the American West to the steppes of Eurasia, the domestic horse transformed
human societies, providing rapid transport, communication, and military power,
and serving as an important subsistence animal. Because of the importance of oral
equipment for horse riding, dentistry is an essential component of modern horse
care. In the open grasslands of northeast Asia, horses remain the primary form of
transport for many herders. Although free-range grazing on gritty forage
mitigates many equine dental issues, contemporary Mongolian horsemen nonetheless
practice some forms of dentistry, including the removal of problematic deciduous
teeth and the vestigial first premolar ("wolf tooth"). Here, we present
archaezoological data from equine skeletal remains spanning the past 3,200 y,
indicating that nomadic dental practices have great antiquity. Anthropogenic
modifications to malerupted deciduous central incisors in young horses from the
Late Bronze Age demonstrate their attempted removal, coinciding with the local
innovation or adoption of horseback riding and the florescence of Mongolian
pastoral society. Horse specimens from this period show no evidence of first
premolar removal, which we first identify in specimens dating to ca. 750 BCE. The
onset of premolar extraction parallels the archaeological appearance of jointed
bronze and iron bits, suggesting that this technological shift prompted
innovations in dentistry that improved horse health and horse control. These
discoveries provide the earliest directly dated evidence for veterinary
dentistry, and suggest that innovations in equine care by nomadic peoples ca.
1150 BCE enabled the use of horses for increasingly sophisticated mounted riding
and warfare.
PMID- 29967159
TI - Reprogrammable Braille on an elastic shell.
AB - We describe a minimal realization of reversibly programmable matter in the form
of a featureless smooth elastic plate that has the capacity to store information
in a Braille-like format as a sequence of stable discrete dimples. Simple
experiments with cylindrical and spherical shells show that we can control the
number, location, and the temporal order of these dimples, which can be written
and erased at will. Theoretical analysis of the governing equations in a
specialized setting and numerical simulations of the complete equations allow us
to characterize the phase diagram for the formation of these localized elastic
states, elastic bits (e-bits), consistent with our observations. Given that the
inherent bistability and hysteresis in these low-dimensional systems arise
exclusively due to the geometrical-scale separation, independent of material
properties or absolute scale, our results might serve as alternate approaches to
small-scale mechanical memories.
PMID- 29967158
TI - Role for fatty acid amide hydrolase (FAAH) in the leptin-mediated effects on
feeding and energy balance.
AB - Endocannabinoid signaling regulates feeding and metabolic processes and has been
linked to obesity development. Several hormonal signals, such as glucocorticoids
and ghrelin, regulate feeding and metabolism by engaging the endocannabinoid
system. Similarly, studies have suggested that leptin interacts with the
endocannabinoid system, yet the mechanism and functional relevance of this
interaction remain elusive. Therefore, we explored the interaction between leptin
and endocannabinoid signaling with a focus on fatty acid amide hydrolase (FAAH),
the primary degradative enzyme for the endocannabinoid N-arachidonoylethanolamine
(anandamide; AEA). Mice deficient in leptin exhibited elevated hypothalamic AEA
levels and reductions in FAAH activity while leptin administration to WT mice
reduced AEA content and increased FAAH activity. Following high fat diet
exposure, mice developed resistance to the effects of leptin administration on
hypothalamic AEA content and FAAH activity. At a functional level,
pharmacological inhibition of FAAH was sufficient to prevent leptin-mediated
effects on body weight and food intake. Using a novel knock-in mouse model
recapitulating a common human polymorphism (FAAH C385A; rs324420), which reduces
FAAH activity, we investigated whether human genetic variance in FAAH affects
leptin sensitivity. While WT (CC) mice were sensitive to leptin-induced
reductions in food intake and body weight gain, low-expressing FAAH (AA) mice
were unresponsive. These data demonstrate that FAAH activity is required for
leptin's hypophagic effects and, at a translational level, suggest that a genetic
variant in the FAAH gene contributes to differences in leptin sensitivity in
human populations.
PMID- 29967160
TI - Subsystem organization of axonal connections within and between the right and
left cerebral cortex and cerebral nuclei (endbrain).
AB - The endbrain (telencephalon) is at the rostral end of the central nervous system
and is primarily responsible for supporting cognition and affect. Structurally,
it consists of right and left cerebral hemispheres, each parceled into multiple
cortical and nuclear gray matter regions. The global network organization of
axonal macroconnections between the 244 regions forming the endbrain was analyzed
with a multiresolution consensus clustering (MRCC) method that provides a
hierarchical description of community clustering (modules or subsystems) within
the network. Experimental evidence was collated from the neuroanatomical
literature for the existence of 10,002 of a possible 59,292 connections within
the network, and they cluster into four top-level subsystems and 60 bottom-level
subsystems arranged in a 50-level hierarchy. Two top-level subsystems are
bihemispheric: One deals with auditory and visual information, and the other
corresponds broadly to the default mode network. The other two top-level
subsystems are bilaterally symmetrical, and each deals broadly with somatic and
visceral information. Because the entire endbrain connection matrix was assembled
from multiple subconnectomes, it was easy to show that the status of a region as
a connectivity hub is not absolute but, instead, depends on the size and coverage
of its anatomical neighborhood. It was also shown numerically that creating an
ultradense connection matrix by converting all "absent" connections to a "very
weak" connection weight has virtually no effect on the clustering hierarchy. The
next logical step in this project is to complete the forebrain connectome by
adding the thalamus and hypothalamus (together, the interbrain) to the endbrain
analysis.
PMID- 29967161
TI - Correction for LeClere et al., Cross-resistance to dicamba, 2,4-D, and fluroxypyr
in Kochia scoparia is endowed by a mutation in an AUX/IAA gene.
PMID- 29967162
TI - An aryl-homoserine lactone quorum-sensing signal produced by a dimorphic
prosthecate bacterium.
AB - Many species of Proteobacteria produce acyl-homoserine lactone (AHL) compounds as
quorum-sensing (QS) signals for cell density-dependent gene regulation. Most
known AHL synthases, LuxI-type enzymes, produce fatty AHLs, and the fatty acid
moiety is derived from an acyl-acyl carrier protein (ACP) intermediate in fatty
acid biosynthesis. Recently, a class of LuxI homologs has been shown to use CoA
linked aromatic or amino acid substrates for AHL synthesis. By using an
informatics approach, we found the CoA class of LuxI homologs exists primarily in
alpha-Proteobacteria. The genome of Prosthecomicrobium hirschii, a dimorphic
prosthecate bacterium, possesses a luxI-like AHL synthase gene that we predicted
to encode a CoA-utilizing enzyme. We show the P. hirschii LuxI homolog catalyzes
synthesis of phenylacetyl-homoserine lactone (PA-HSL). Our experiments show P.
hirschii obtains phenylacetate from its environment and uses a CoA ligase to
produce the phenylacetyl-CoA substrate for the LuxI homolog. By using an AHL
degrading enzyme, we showed that PA-HSL controls aggregation, biofilm formation,
and pigment production in P. hirschii These findings advance a limited
understanding of the CoA-dependent AHL synthases. We describe how to identify
putative members of the class, we describe a signal synthesized by using an
environmental aromatic acid, and we identify phenotypes controlled by the aryl
HSL.
PMID- 29967163
TI - Costs and benefits of provocation in bacterial warfare.
AB - Competition in animals involves a wide variety of aggressive behaviors. One of
the most sophisticated strategies for a focal actor is to provoke a competitor
into uncontrolled aggression toward other competitors. Like animals, bacteria
rely on a broad spectrum of molecular weapons, some of which provoke potential
rivals by triggering retaliation. While bacterial provocation is well documented,
its potential adaptive value has received little attention. Here, we examine the
costs and benefits of provocation using mathematical modeling and experiments
with Escherichia coli strains encoding colicin toxins. We show that provocation
is typically costly in one-to-one encounters because a provoking strain receives
a strong reciprocal attack compared with nonprovoking strains. By contrast,
provocation can be strongly beneficial in communities including more than two
toxin-producing strains, especially when the provoker is shielded from, or
resistant to, its opponents' toxins. In these scenarios, we demonstrate that the
benefit of provocation derives from a "divide-and-conquer" effect by which
aggression-provoking toxin producers force their competitors into increased
reciprocal aggression, leading to their cross-elimination. Furthermore, we show
that this effect can be mimicked by using antibiotics that promote warfare among
strains in a bacterial community, highlighting the potential of provocation as an
antimicrobial approach.
PMID- 29967164
TI - Disruption of divisome assembly rescued by FtsN-FtsA interaction in Escherichia
coli.
AB - Cell division requires the assembly of a protein complex called the divisome. The
divisome assembles in a hierarchical manner, with FtsA functioning as a hub to
connect the Z-ring with the rest of the divisome and FtsN arriving last to
activate the machine to synthesize peptidoglycan. FtsEX arrives as the Z-ring
forms and acts on FtsA to initiate recruitment of the other divisome components.
In the absence of FtsEX, recruitment is blocked; however, a multitude of
conditions allow FtsEX to be bypassed. Here, we find that all such FtsEX bypass
conditions, as well as the bypass of FtsK, depend upon the interaction of FtsN
with FtsA, which promotes the back-recruitment of the late components of the
divisome. Furthermore, our results suggest that these bypass conditions enhance
the weak interaction of FtsN with FtsA and its periplasmic partners so that the
divisome proteins are brought to the Z-ring when the normal hierarchical pathway
is disrupted.
PMID- 29967165
TI - Antimalarial proteasome inhibitor reveals collateral sensitivity from
intersubunit interactions and fitness cost of resistance.
AB - We describe noncovalent, reversible asparagine ethylenediamine (AsnEDA)
inhibitors of the Plasmodium falciparum proteasome (Pf20S) beta5 subunit that
spare all active subunits of human constitutive and immuno-proteasomes. The
compounds are active against erythrocytic, sexual, and liver-stage parasites,
against parasites resistant to current antimalarials, and against P. falciparum
strains from patients in Africa. The beta5 inhibitors synergize with a beta2
inhibitor in vitro and in mice and with artemisinin. P. falciparum selected for
resistance to an AsnEDA beta5 inhibitor surprisingly harbored a point mutation in
the noncatalytic beta6 subunit. The beta6 mutant was resistant to the species
selective Pf20S beta5 inhibitor but remained sensitive to the species
nonselective beta5 inhibitors bortezomib and carfilzomib. Moreover, resistance to
the Pf20S beta5 inhibitor was accompanied by increased sensitivity to a Pf20S
beta2 inhibitor. Finally, the beta5 inhibitor-resistant mutant had a fitness cost
that was exacerbated by irradiation. Thus, used in combination, multistage-active
inhibitors of the Pf20S beta5 and beta2 subunits afford synergistic antimalarial
activity with a potential to delay the emergence of resistance to artemisinins
and each other.
PMID- 29967166
TI - Repression of human and mouse brain inflammaging transcriptome by broad gene-body
histone hyperacetylation.
AB - Brain "inflammaging," a low-grade and chronic inflammation, is a major hallmark
for aging-related neurodegenerative diseases. Here, by profiling H3K27ac and gene
expression patterns in human and mouse brains, we found that age-related up
regulated (Age-Up) and down-regulated (Age-Down) genes have distinct H3K27ac
patterns. Although both groups show promoter H3K27ac, the Age-Up genes, enriched
for inflammation-related functions, are additionally marked by broad H3K27ac
distribution over their gene bodies, which is progressively reduced during aging.
Age-related gene expression changes can be predicted by gene-body H3K27ac level.
Contrary to the presumed transcription activation function of promoter H3K27ac,
we found that broad gene-body hyper H3K27ac suppresses overexpression of
inflammaging genes. Altogether, our findings revealed opposite regulations by
H3K27ac of Age-Up and Age-Down genes and a mode of broad gene-body H3K27ac in
repressing transcription.
PMID- 29967168
TI - Correction for Edwards et al., Insight from the maximal activation of the signal
transduction excitable network in Dictyostelium discoideum.
PMID- 29967167
TI - Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and
nociception.
AB - N-acyl amino acids (NAAs) are a structurally diverse class of bioactive signaling
lipids whose endogenous functions have largely remained uncharacterized. To
clarify the physiologic roles of NAAs, we generated mice deficient in the
circulating enzyme peptidase M20 domain-containing 1 (PM20D1). Global PM20D1-KO
mice have dramatically reduced NAA hydrolase/synthase activities in tissues and
blood with concomitant bidirectional dysregulation of endogenous NAAs. Compared
with control animals, PM20D1-KO mice exhibit a variety of metabolic and pain
phenotypes, including insulin resistance, altered body temperature in cold, and
antinociceptive behaviors. Guided by these phenotypes, we identify N-oleoyl
glutamine (C18:1-Gln) as a key PM20D1-regulated NAA. In addition to its
mitochondrial uncoupling bioactivity, C18:1-Gln also antagonizes certain members
of the transient receptor potential (TRP) calcium channels including TRPV1.
Direct administration of C18:1-Gln to mice is sufficient to recapitulate a subset
of phenotypes observed in PM20D1-KO animals. These data demonstrate that PM20D1
is a dominant enzymatic regulator of NAA levels in vivo and elucidate physiologic
functions for NAA signaling in metabolism and nociception.
PMID- 29967169
TI - Backbone-free duplex-stacked monomer nucleic acids exhibiting Watson-Crick
selectivity.
AB - We demonstrate that nucleic acid (NA) mononucleotide triphosphates (dNTPs and
rNTPs), at sufficiently high concentration and low temperature in aqueous
solution, can exhibit a phase transition in which chromonic columnar liquid
crystal ordering spontaneously appears. Remarkably, this polymer-free state
exhibits, in a self-assembly of NA monomers, the key structural elements of
biological nucleic acids, including: long-ranged duplex stacking of base pairs,
complementarity-dependent partitioning of molecules, and Watson-Crick
selectivity, such that, among all solutions of adenosine, cytosine, guanine, and
thymine NTPs and their binary mixtures, duplex columnar ordering is most stable
in the A-T and C-G combinations.
PMID- 29967170
TI - Ethological observations of social behavior in the operating room.
AB - Operating rooms (ORs) are inhabited by hierarchical, mixed-gender clinical teams
that are often prone to conflict. In evolutionary terms, one expects more within-
than between-gender rivalries, especially since the OR is a place where all sorts
of social interactions occur, not merely technical communications. To document
the full range of behavior, the present study used ethological observation
techniques, recording live all social behavior by the team. Using an ethogram,
6,348 spontaneous social interactions and nontechnical communications were
timestamped during 200 surgical procedures. Cooperation sequences (59.0%) were
more frequent than conflict sequences (2.8%), which ranged from constructive
differences of opinion to discord and distraction that could jeopardize patient
safety. Behavior varied by clinical role and with the gender composition in the
OR. Conflict was initiated mostly down the hierarchy between individuals several
ranks apart. Cooperation tended to increase with a rising proportion of females
in the OR, but the most pronounced effect concerned the interaction between both
genders. If the attending surgeon's gender differed from that of the majority of
other personnel in the OR, cooperation was significantly more common.
PMID- 29967171
TI - Mechanistic insights in transcription-coupled nucleotide excision repair of
ribosomal DNA.
AB - Nucleotide excision repair (NER) guarantees genome integrity against UV light
induced DNA damage. After UV irradiation, cells have to cope with a general
transcriptional block. To ensure UV lesions repair specifically on transcribed
genes, NER is coupled with transcription in an extremely organized pathway known
as transcription-coupled repair. In highly metabolic cells, more than 60% of
total cellular transcription results from RNA polymerase I activity. Repair of
the mammalian transcribed ribosomal DNA has been scarcely studied. UV lesions
severely block RNA polymerase I activity and the full transcription-coupled
repair machinery corrects damage on actively transcribed ribosomal DNAs. After UV
irradiation, RNA polymerase I is more bound to the ribosomal DNA and both are
displaced to the nucleolar periphery. Importantly, the reentry of RNA polymerase
I and the ribosomal DNA is dependent on the presence of UV lesions on DNA and
independent of transcription restart.
PMID- 29967172
TI - Molecular profiling of reticular gigantocellularis neurons indicates that eNOS
modulates environmentally dependent levels of arousal.
AB - Neurons of the medullary reticular nucleus gigantocellularis (NGC) and their
targets have recently been a focus of research on mechanisms supporting
generalized CNS arousal (GA) required for proper cognitive functions. Using the
retro-TRAP method, we characterized transcripts enriched in NGC neurons which
have projections to the thalamus. The unique expression and activation of the
endothelial nitric oxide (eNOS) signaling pathway in these cells and their
intimate connections with blood vessels indicate that these neurons exert direct
neurovascular coupling. Production of nitric oxide (NO) within eNOS-positive NGC
neurons increases after environmental perturbations, indicating a role for
eNOS/NO in modulating environmentally appropriate levels of GA. Inhibition of NO
production causes dysregulated behavioral arousal after exposure to environmental
perturbation. Further, our findings suggest interpretations for associations
between psychiatric disorders and mutations in the eNOS locus.
PMID- 29967173
TI - Host quality induces phenotypic plasticity in a wing polyphenic insect.
AB - Food quality is a critical environmental condition that impacts an animal's
growth and development. Many insects facing this challenge have evolved a
phenotypically plastic, adaptive response. For example, many species of insect
exhibit facultative wing growth, which reflects a physiological and evolutionary
trade-off between dispersal and reproduction, triggered by environmental
conditions. What the environmental cues are and how they are transduced to
produce these alternative forms, and their associated ecological shift from
dispersal to reproduction, remains an important unsolved problem in evolutionary
ecology. In this study, we investigated the role that host quality has on the
induction of wing development in a wing polyphenic insect exhibiting strong
tradeoffs in investment between dispersal and reproduction, the brown
planthopper, a serious rice pest in Asia. As rice plants grow, the short-winged
brown planthopper dominates the population, but a shift occurs as the plants
mature and senesce in the field such that long-winged brown planthoppers emerge
and migrate. It remains unknown how changes in the rice plant induce development
of the long-winged morph, despite recent discoveries on the role of the insulin
and JNK signaling pathways in wing development. We found that by mimicking the
glucose concentration of senescing rice plants, we significantly increased the
proportion of long-winged female planthoppers. The effects of glucose on wing
morph are additive with previously described effects of density. Our results show
that host quality both directly regulates phenotypic plasticity and interacts
with other factors such as density to produce the appropriate phenotype for
specific environmental conditions.
PMID- 29967174
TI - Chromatin organization by an interplay of loop extrusion and compartmental
segregation.
AB - Mammalian chromatin is spatially organized at many scales showing two prominent
features in interphase: (i) alternating regions (1-10 Mb) of active and inactive
chromatin that spatially segregate into different compartments, and (ii) domains
(<1 Mb), that is, regions that preferentially interact internally [topologically
associating domains (TADs)] and are central to gene regulation. There is growing
evidence that TADs are formed by active extrusion of chromatin loops by cohesin,
whereas compartmentalization is established according to local chromatin states.
Here, we use polymer simulations to examine how loop extrusion and compartmental
segregation work collectively and potentially interfere in shaping global
chromosome organization. A model with differential attraction between euchromatin
and heterochromatin leads to phase separation and reproduces compartmentalization
as observed in Hi-C. Loop extrusion, essential for TAD formation, in turn,
interferes with compartmentalization. Our integrated model faithfully reproduces
Hi-C data from puzzling experimental observations where altering loop extrusion
also led to changes in compartmentalization. Specifically, depletion of chromatin
associated cohesin reduced TADs and revealed finer compartments, while increased
processivity of cohesin strengthened large TADs and reduced compartmentalization;
and depletion of the TAD boundary protein CTCF weakened TADs while leaving
compartments unaffected. We reveal that these experimental perturbations are
special cases of a general polymer phenomenon of active mixing by loop extrusion.
Our results suggest that chromatin organization on the megabase scale emerges
from competition of nonequilibrium active loop extrusion and epigenetically
defined compartment structure.
PMID- 29967175
TI - Opposite outcomes of coinfection at individual and population scales.
AB - Coinfecting parasites and pathogens remain a leading challenge for global public
health due to their consequences for individual-level infection risk and disease
progression. However, a clear understanding of the population-level consequences
of coinfection is lacking. Here, we constructed a model that includes three
individual-level effects of coinfection: mortality, fecundity, and transmission.
We used the model to investigate how these individual-level consequences of
coinfection scale up to produce population-level infection patterns. To
parameterize this model, we conducted a 4-y cohort study in African buffalo to
estimate the individual-level effects of coinfection with two bacterial
pathogens, bovine tuberculosis (bTB) and brucellosis, across a range of
demographic and environmental contexts. At the individual level, our empirical
results identified bTB as a risk factor for acquiring brucellosis, but we found
no association between brucellosis and the risk of acquiring bTB. Both infections
were associated with reductions in survival and neither infection was associated
with reductions in fecundity. The model reproduced coinfection patterns in the
data and predicted opposite impacts of coinfection at individual and population
scales: Whereas bTB facilitated brucellosis infection at the individual level,
our model predicted the presence of brucellosis to have a strong negative impact
on bTB at the population level. In modeled populations where brucellosis was
present, the endemic prevalence and basic reproduction number ([Formula: see
text]) of bTB were lower than in populations without brucellosis. Therefore,
these results provide a data-driven example of competition between coinfecting
pathogens that occurs when one pathogen facilitates secondary infections at the
individual level.
PMID- 29967176
TI - Growth suppression of ice crystal basal face in the presence of a moderate ice
binding protein does not confer hyperactivity.
AB - Ice-binding proteins (IBPs) affect ice crystal growth by attaching to crystal
faces. We present the effects on the growth of an ice single crystal caused by an
ice-binding protein from the sea ice microalga Fragilariopsis cylindrus (fcIBP)
that is characterized by the widespread domain of unknown function 3494 (DUF3494)
and known to cause a moderate freezing point depression (below 1 degrees C). By
the application of interferometry, bright-field microscopy, and fluorescence
microscopy, we observed that the fcIBP attaches to the basal faces of ice
crystals, thereby inhibiting their growth in the c direction and resulting in an
increase in the effective supercooling with increasing fcIBP concentration. In
addition, we observed that the fcIBP attaches to prism faces and inhibits their
growth. In the event that the effective supercooling is small and crystals are
faceted, this process causes an emergence of prism faces and suppresses crystal
growth in the a direction. When the effective supercooling is large and ice
crystals have developed into a dendritic shape, the suppression of prism face
growth results in thinner dendrite branches, and growth in the a direction is
accelerated due to enhanced latent heat dissipation. Our observations clearly
indicate that the fcIBP occupies a separate position in the classification of
IBPs due to the fact that it suppresses the growth of basal faces, despite its
moderate freezing point depression.
PMID- 29967178
TI - QnAs with Lia Addadi.
PMID- 29967177
TI - Serum exosomes mediate delivery of arginase 1 as a novel mechanism for
endothelial dysfunction in diabetes.
AB - Exosomes, abundant in blood, deliver various molecules to recipient cells.
Endothelial cells are directly exposed to circulating substances. However, how
endothelial cells respond to serum exosomes (SExos) and the implications in
diabetes-associated vasculopathy have never been explored. In the present study,
we showed that SExos from diabetic db/db mice (db/db SExos) were taken up by
aortic endothelial cells, which severely impaired endothelial function in
nondiabetic db/m+ mice. The exosomal proteins, rather than RNAs, mostly account
for db/db SExos-induced endothelial dysfunction. Comparative proteomics analysis
showed significant increase of arginase 1 in db/db SExos. Silence or
overexpression of arginase 1 confirmed its essential role in db/db SExos-induced
endothelial dysfunction. This study is a demonstration that SExos deliver
arginase 1 protein to endothelial cells, representing a cellular mechanism during
development of diabetic endothelial dysfunction. The results expand the scope of
blood-borne substances that monitor vascular homeostasis.
PMID- 29967179
TI - Two polymorphic cholesterol monohydrate crystal structures form in macrophage
culture models of atherosclerosis.
AB - The formation of atherosclerotic plaques in the blood vessel walls is the result
of LDL particle uptake, and consequently of cholesterol accumulation in
macrophage cells. Excess cholesterol accumulation eventually results in
cholesterol crystal deposition, the hallmark of mature atheromas. We followed the
formation of cholesterol crystals in J774A.1 macrophage cells with time, during
accumulation of LDL particles, using a previously developed correlative cryosoft
X-ray tomography (cryo-SXT) and stochastic optical reconstruction microscopy
(STORM) technique. We show, in the initial accumulation stages, formation of
small quadrilateral crystal plates associated with the cell plasma membrane,
which may subsequently assemble into large aggregates. These plates match
crystals of the commonly observed cholesterol monohydrate triclinic structure.
Large rod-like cholesterol crystals form at a later stage in intracellular
locations. Using cryotransmission electron microscopy (cryo-TEM) and cryoelectron
diffraction (cryo-ED), we show that the structure of the large elongated rods
corresponds to that of monoclinic cholesterol monohydrate, a recently determined
polymorph of the triclinic crystal structure. These monoclinic crystals form with
an unusual hollow cylinder or helical architecture, which is preserved in the
mature rod-like crystals. The rod-like morphology is akin to that observed in
crystals isolated from atheromas. We suggest that the crystals in the
atherosclerotic plaques preserve in their morphology the memory of the structure
in which they were formed. The identification of the polymorph structure, besides
explaining the different crystal morphologies, may serve to elucidate mechanisms
of cholesterol segregation and precipitation in atherosclerotic plaques.
PMID- 29967181
TI - First evidence for silica condensation within the solar protoplanetary disk.
AB - Calcium-aluminum-rich inclusions (CAIs) and amoeboid olivine aggregates (AOAs), a
refractory component of chondritic meteorites, formed in a high-temperature
region of the protoplanetary disk characterized by approximately solar chemical
and oxygen isotopic (Delta17O ~ -240/00) compositions, most likely near the
protosun. Here we describe a 16O-rich (Delta17O ~ -22 +/- 20/00) AOA from the
carbonaceous Renazzo-type (CR) chondrite Yamato-793261 containing both (i) an
ultrarefractory CAI and (ii) forsterite, low-Ca pyroxene, and silica, indicating
formation by gas-solid reactions over a wide temperature range from ~1,800 to
~1,150 K. This AOA provides direct evidence for gas-solid condensation of silica
in a CAI/AOA-forming region. In a gas of solar composition, the Mg/Si ratio
exceeds 1, and, therefore, silica is not predicted to condense under equilibrium
conditions, suggesting that the AOA formed in a parcel of gas with fractionated
Mg/Si ratio, most likely due to condensation of forsterite grains. Thermodynamic
modeling suggests that silica formed by condensation of nebular gas depleted by
~10* in H and He that cooled at 50 K/hour at total pressure of 10-4 bar.
Condensation of silica from a hot, chemically fractionated gas could explain the
origin of silica identified from infrared spectroscopy of remote protostellar
disks.
PMID- 29967180
TI - Identification of a new subset of lymph node stromal cells involved in regulating
plasma cell homeostasis.
AB - Antibody-secreting plasma cells (PCs) arise rapidly during adaptive immunity to
control infections. The early PCs are retained within the reactive lymphoid organ
where their localization and homeostasis rely on extrinsic factors, presumably
produced by local niche cells. While myeloid cells have been proposed to form
those niches, the contribution by colocalizing stromal cells has remained
unclear. Here, we characterized a subset of fibroblastic reticular cells (FRCs)
that forms a dense meshwork throughout medullary cords of lymph nodes (LNs) where
PCs reside. This medullary FRC type is shown to be anatomically, phenotypically,
and functionally distinct from T zone FRCs, both in mice and humans. By using
static and dynamic imaging approaches, we provide evidence that medullary FRCs
are the main cell type in contact with PCs guiding them in their migration.
Medullary FRCs also represent a major local source of the PC survival factors IL
6, BAFF, and CXCL12, besides also producing APRIL. In vitro, medullary FRCs alone
or in combination with macrophages promote PC survival while other LN cell types
do not have this property. Thus, we propose that this FRC subset, together with
medullary macrophages, forms PC survival niches within the LN medulla, and
thereby helps in promoting the rapid development of humoral immunity, which is
critical in limiting early pathogen spread.
PMID- 29967182
TI - Redundancy in synaptic connections enables neurons to learn optimally.
AB - Recent experimental studies suggest that, in cortical microcircuits of the
mammalian brain, the majority of neuron-to-neuron connections are realized by
multiple synapses. However, it is not known whether such redundant synaptic
connections provide any functional benefit. Here, we show that redundant synaptic
connections enable near-optimal learning in cooperation with synaptic rewiring.
By constructing a simple dendritic neuron model, we demonstrate that with
multisynaptic connections synaptic plasticity approximates a sample-based
Bayesian filtering algorithm known as particle filtering, and wiring plasticity
implements its resampling process. Extending the proposed framework to a detailed
single-neuron model of perceptual learning in the primary visual cortex, we show
that the model accounts for many experimental observations. In particular, the
proposed model reproduces the dendritic position dependence of spike-timing
dependent plasticity and the functional synaptic organization on the dendritic
tree based on the stimulus selectivity of presynaptic neurons. Our study provides
a conceptual framework for synaptic plasticity and rewiring.
PMID- 29967184
TI - Physical growth, neurodevelopment and cognition outcomes in children with
abdominal wall defects: a tale with two endings?
PMID- 29967183
TI - Induction of oligoclonal CD8 T cell responses against pulmonary metastatic cancer
by a phospholipid-conjugated TLR7 agonist.
AB - Recent advances in cancer immunotherapy have improved patient survival. However,
only a minority of patients with pulmonary metastatic disease respond to
treatment with checkpoint inhibitors. As an alternate approach, we have tested
the ability of systemically administered 1V270, a toll-like receptor 7 (TLR7)
agonist conjugated to a phospholipid, to inhibit lung metastases in two variant
murine 4T1 breast cancer models, as well as in B16 melanoma, and Lewis lung
carcinoma models. In the 4T1 breast cancer models, 1V270 therapy inhibited lung
metastases if given up to a week after primary tumor initiation. The treatment
protocol was facilitated by the minimal toxic effects exerted by the phospholipid
TLR7 agonist compared with the unconjugated agonist. 1V270 exhibited a wide
therapeutic window and minimal off-target receptor binding. The 1V270 therapy
inhibited colonization by tumor cells in the lungs in an NK cell dependent
manner. Additional experiments revealed that single administration of 1V270 led
to tumor-specific CD8+ cell-dependent adaptive immune responses that suppressed
late-stage metastatic tumor growth in the lungs. T cell receptor (TCR) repertoire
analyses showed that 1V270 therapy induced oligoclonal T cells in the lungs and
mediastinal lymph nodes. Different animals displayed commonly shared TCR clones
following 1V270 therapy. Intranasal administration of 1V270 also suppressed lung
metastasis and induced tumor-specific adaptive immune responses. These results
indicate that systemic 1V270 therapy can induce tumor-specific cytotoxic T cell
responses to pulmonary metastatic cancers and that TCR repertoire analyses can be
used to monitor, and to predict, the response to therapy.
PMID- 29967185
TI - Bone metabolism in Langerhans cell histiocytosis.
AB - Langerhans cell histiocytosis (LCH) is a rare disease of not well-defined
etiology that involves immune cell activation and frequently affects the
skeleton. Bone involvement in LCH usually presents in the form of osteolytic
lesions along with low bone mineral density. Various molecules involved in bone
metabolism are implicated in the pathogenesis of LCH or may be affected during
the course of the disease, including interleukins (ILs), tumor necrosis factor
alpha, receptor activator of NF-kappaB (RANK) and its soluble ligand RANKL,
osteoprotegerin (OPG), periostin and sclerostin. Among them IL-17A, periostin and
RANKL have been proposed as potential serum biomarkers for LCH, particularly as
the interaction between RANK, RANKL and OPG not only regulates bone homeostasis
through its effects on the osteoclasts but also affects the activation and
survival of immune cells. Significant changes in circulating and lesional RANKL
levels have been observed in LCH patients irrespective of bone involvement.
Standard LCH management includes local or systematic administration of
corticosteroids and chemotherapy. Given the implication of RANK, RANKL and OPG in
the pathogenesis of the disease and the osteolytic nature of bone lesions, agents
aiming at inhibiting the RANKL pathway and/or osteoclastic activation, such as
bisphosphonates and denosumab, may have a role in the therapeutic approach of LCH
although further clinical investigation is warranted.
PMID- 29967188
TI - Correction: Regulation of Minichromosome Maintenance Gene Family by MicroRNA-1296
and Genistein in Prostate Cancer.
PMID- 29967186
TI - Intraoperative low field MRI in transsphenoidal pituitary surgery.
AB - BACKGROUND: Intraoperative low field MRI (iMRI, 0.15 T) during transsphenoidal
surgery on pituitary adenomas (PAs) may significantly improve tumor removal.
However, extensive surgery can lead to pituitary hormone deficiency. Furthermore,
introduction of iMRI will prolong duration of surgery, which may elevate risk of
postoperative infections. METHODS: Overall, 180 transsphenoidal surgeries for PAs
from 2007 to 2015 were included. IMRI was available from 2011 to 2015, during
this period 67/78 (86%) surgeries were with iMRI (iMRI, n = 67). A total of 113
surgeries were performed without iMRI (controls). All surgical procedures were
performed by microscopic technique. Tumor size, hormonal status and vision were
assessed before surgery and 3-5 months postoperatively. RESULTS: Gross total
resection (GTR), mean tumor remnant volume and ?-volumes were comparable between
iMRI and controls: 15% (10/66) vs 23% (26/109) (P = 0.17), 2.97 cm3 (0.9-5) vs
2.1 cm3 (1.6-2.6) (P = 0.3) and 4.5 cm3 (3.6-5.5) vs 5.1 cm3 (4.2-6) (P = 0.4),
respectively. Duration of surgery was significantly longer during iMRI vs
controls: 126 min (117-135) vs 98 min (92-103) (P < 0.001). New pituitary-adrenal
deficiency in iMRI vs controls was seen in 35% (17/48) and 35% (23/66) of
surgeries, respectively (P = 0.95). New thyroid deficiency was found in 33%
(13/29) and 41% (28/69) and visual field deficiencies improved in 44% (19/43) and
38% (23/60) in iMRI vs controls, respectively (P > 0.1). CONCLUSION: Tumor
remnant after pituitary surgery was not significantly reduced using
intraoperative low field MRI. Duration of surgery was increased in iMRI, but was
not associated with increased infection rate. Pituitary hormonal function and
vision were comparable between iMRI and controls.
PMID- 29967189
TI - Correction: Heterochromatin Protein HP1gamma Promotes Colorectal Cancer
Progression and Is Regulated by miR-30a.
PMID- 29967190
TI - Correction: FIH Is an Oxygen Sensor in Ovarian Cancer for G9a/GLP-Driven
Epigenetic Regulation of Metastasis-Related Genes.
PMID- 29967191
TI - Correction: Cancer Self-Defense: An Immune Stealth.
PMID- 29967192
TI - Correction: Downregulation of MicroRNA miR-520h by E1A Contributes to Anticancer
Activity.
PMID- 29967193
TI - Costs, contracts and the narrative of prosperity: an economic analysis of
smallholder tobacco farming livelihoods in Kenya.
AB - BACKGROUND: The tobacco industry has used the alleged negative impacts on
economic livelihoods for tobacco farmers as a narrative to oppose tobacco control
measures in low/middle-income countries. However, rigorous empirical evidence to
support or refute this claim remains scarce. Accordingly, we assess how much
money households earn from selling tobacco, and the costs they incur to produce
the crop, including labour inputs. We also evaluate farmers' decision to operate
under contract directly with tobacco manufacturers and tobacco leaf-buying
companies or to operate as independent farmers. METHODS: A stratified random
sampling method was used to implement a nationally representative household-level
economic survey of 585 farmers across the three main tobacco growing regions in
Kenya. The survey was augmented with focus group discussions in all three regions
to refine and enrich the context of the findings. RESULTS: Both contract and
independent farmers experience small profit margins per acre, with contract
farmers operating at a loss. Even when family labour is excluded from the
calculation, income levels remain low, particularly considering the typically
large households. Generally, tobacco farmers enter into contracts with tobacco
companies because they have a 'guaranteed' buyer for their tobacco leaf and
receive the necessary agricultural inputs (fertiliser, seeds, herbicides and so
on) without paying cash up-front. CONCLUSIONS: Tobacco farming households enter
into contract with tobacco companies to realise perceived economic benefits. The
narrative that tobacco farming is a lucrative economic undertaking for
smallholder farmers, however, is inaccurate in the context of Kenya.
PMID- 29967194
TI - Systematic approach demonstrates enrichment of multiple interactions between non
HLA risk variants and HLA-DRB1 risk alleles in rheumatoid arthritis.
AB - OBJECTIVE: In anti-citrullinated protein antibody positive rheumatoid arthritis
(ACPA-positive RA), a particular subset of HLA-DRB1 alleles, called shared
epitope (SE) alleles, is a highly influential genetic risk factor. Here, we
investigated whether non-HLA single nucleotide polymorphisms (SNP), conferring
low disease risk on their own, interact with SE alleles more frequently than
expected by chance and if such genetic interactions influence the HLA-DRB1 SE
effect concerning risk to ACPA-positive RA. METHODS: We computed the attributable
proportion (AP) due to additive interaction at genome-wide level for two
independent ACPA-positive RA cohorts: the Swedish epidemiological investigation
of rheumatoid arthritis (EIRA) and the North American rheumatoid arthritis
consortium (NARAC). Then, we tested for differences in the AP p value
distributions observed for two groups of SNPs, non-associated and associated with
disease. We also evaluated whether the SNPs in interaction with HLA-DRB1 were cis
eQTLs in the SE alleles context in peripheral blood mononuclear cells from
patients with ACPA-positive RA (SE-eQTLs). RESULTS: We found a strong enrichment
of significant interactions (AP p<0.05) between the HLA-DRB1 SE alleles and the
group of SNPs associated with ACPA-positive RA in both cohorts (Kolmogorov
Smirnov test D=0.35 for EIRA and D=0.25 for NARAC, p<2.2e-16 for both).
Interestingly, 564 out of 1492 SNPs in consistent interaction for both cohorts
were significant SE-eQTLs. Finally, we observed that the effect size of HLA-DRB1
SE alleles for disease decreases from 5.2 to 2.5 after removal of the risk
alleles of the two top interacting SNPs (rs2476601 and rs10739581). CONCLUSION:
Our data demonstrate that there are massive genetic interactions between the HLA
DRB1 SE alleles and non-HLA genetic variants in ACPA-positive RA.
PMID- 29967195
TI - IL (Interleukin)-10-STAT3-Galectin-3 Axis Is Essential for Osteopontin-Producing
Reparative Macrophage Polarization After Myocardial Infarction.
AB - BACKGROUND: Both osteopontin (OPN) and galectin-3 have been implicated in
phagocytic clearance of dead cells and reparative fibrosis during wound healing.
CD206+ macrophages are involved in tissue repair through phagocytosis and
fibrosis after myocardial infarction (MI). However, the relationship among OPN,
galectin-3, and macrophage polarization in the context of MI remains unclear.
METHODS: The time course of Spp1 (encoding OPN) expression in the heart after MI
showed a strong activation of Spp1 on day 3 after MI. To identify where in the
body and in which cells the transcriptional activity of Spp1 increased after MI,
we analyzed EGFP (enhanced green fluorescent protein)- Spp1 knockin reporter mice
on day 3 after MI. RESULTS: The transcriptional activity of Spp1 increased only
in CD206+ macrophages in the infarct myocardium, and most of CD206+ macrophages
have strong transcriptional activation of Spp1 after MI. The temporal expression
pattern of Lgal3 (encoding galectin-3) in cardiac macrophages after MI was
similar to that of Spp1, and OPN is almost exclusively produced by galectin
3hiCD206+ macrophages. Although both interleukin (IL)-4 and IL-10 were reported
to promote CD206+ macrophage-mediated cardiac repair after MI, IL-10- but not IL
4-stimulated CD11b+Ly6G- cells could differentiate into OPN-producing galectin
3hiCD206+ macrophages and showed enhanced phagocytic ability. Inhibition of STAT3
tyrosine phosphorylation suppressed IL-10-induced expression of intracellular
galectin-3 and transcriptional activation of Spp1. Knockdown of galectin-3
suppressed their ability to differentiate into OPN-producing cells, but not STAT3
activation. The tyrosine phosphorylation of STAT3 and the appearance rate of
galectin-3hiCD206+ cells on cardiac CD11b+Ly6G- cells in Spp1 knockout mice were
the same as those in wild-type mice. Spp1 knockout mice showed vulnerability to
developing post-MI left ventricular chamber dilatation and the terminal
deoxynucleo-tidyltransferase 2'-Deoxyuridine-5'-triphosphate nick-end labeling
(TUNEL)-positive cells in the infarcted myocardium after MI remained higher in
number in Spp1 knockout mice than in wild-type mice. CONCLUSIONS: OPN is almost
exclusively produced by galectin-3hiCD206+ macrophages, which specifically appear
in the infarct myocardium after MI. The IL-10-STAT3-galectin-3 axis is essential
for OPN-producing reparative macrophage polarization after myocardial infarction,
and these macrophages contribute to tissue repair by promoting fibrosis and
clearance of apoptotic cells. These results suggest that galectin-3 may
contribute to reparative fibrosis in the infarct myocardium by controlling OPN
levels.
PMID- 29967198
TI - What's happening in Neurology(r).
PMID- 29967196
TI - Global Burden of Atherosclerotic Cardiovascular Disease in People Living With
HIV.
AB - BACKGROUND: With advances in antiretroviral therapy, most deaths in people with
HIV are now attributable to noncommunicable illnesses, especially cardiovascular
disease. We determine the association between HIV and cardiovascular disease, and
estimate the national, regional, and global burden of cardiovascular disease
attributable to HIV. METHODS: We conducted a systematic review across 5 databases
from inception to August 2016 for longitudinal studies of cardiovascular disease
in HIV infection. A random-effects meta-analysis across 80 studies was used to
derive the pooled rate and risk of cardiovascular disease in people living with
HIV. We then estimated the temporal changes in the population-attributable
fraction and disability-adjusted life-years (DALYs) from HIV-associated
cardiovascular disease from 1990 to 2015 at a regional and global level. National
cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193
United Nations member states. The main outcome measure was the pooled estimate of
the rate and risk of cardiovascular disease in people living with HIV and the
national, regional, and global estimates of DALYs from cardiovascular disease
associated with HIV. RESULTS: In 793 635 people living with HIV and a total
follow-up of 3.5 million person-years, the crude rate of cardiovascular disease
was 61.8 (95% CI, 45.8-83.4) per 10 000 person-years. In comparison with
individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95%
CI, 1.68-2.77). Over the past 26 years, the global population-attributable
fraction from cardiovascular disease attributable to HIV increased from 0.36%
(95% CI, 0.21%-0.56%) to 0.92% (95% CI, 0.55%-1.41%), and DALYs increased from
0.74 (95% CI, 0.44-1.16) to 2.57 (95% CI, 1.53-3.92) million. There was marked
regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95%
CI, 0.43-1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23-0.62) regions.
The highest population-attributable fraction and burden were observed in
Swaziland, Botswana, and Lesotho. CONCLUSIONS: People living with HIV are twice
as likely to develop cardiovascular disease. The global burden of HIV-associated
cardiovascular disease has tripled over the past 2 decades and is now responsible
for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa
and the Asia Pacific regions. CLINICAL TRIAL REGISTRATION: URL:
https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.
PMID- 29967197
TI - Linking Endogenous Factor Xa Activity, a Biologically Relevant Pharmacodynamic
Marker, to Edoxaban Plasma Concentrations and Clinical Outcomes in the ENGAGE AF
TIMI 48 Trial.
AB - BACKGROUND: We previously reported exogenous antifactor Xa (FXa) activity as a
pharmacokinetic surrogate marker for edoxaban plasma concentrations. Inhibition
of endogenous FXa activity is a more biologically relevant pharmacodynamic
measure of edoxaban activity. Here we describe the value of endogenous FXa
activity as a pharmacodynamic marker linking edoxaban concentrations and clinical
outcomes in the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa
Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction
Study 48). METHODS: In ENGAGE AF-TIMI 48, edoxaban was administered in higher
dose (60/30 mg QD) and lower dose (30/15 mg QD) regimens. Both regimens
incorporated a 50% dose reduction in patients with characteristics known to
increase edoxaban concentration. Pharmacokinetic-pharmacodynamic modeling was
performed in a subgroup of 3029 patients who had samples collected for endogenous
FXa activity (measured using an assay after endogenous FX was activated with
Russell viper venom). RESULTS: Endogenous FXa activity decreased with increasing
edoxaban concentrations of <=440 ng/mL, indicating that inhibition of endogenous
FXa activity is saturated above this concentration threshold. Baseline endogenous
FXa activity averaged 92.1+/-20.9% (relative to normal control samples) and was
lower with older age, with lower body weight, and in male patients. Model
predicted 24-hour average percentages of inhibition of endogenous FXa activity
were 35.8+/-5.18, 29.1+/-3.92, 21.9+/-3.80, and 16.4+/-2.70 for the higher dose
edoxaban regimen 60 mg, dose-reduced higher dose edoxaban regimen 30 mg, lower
dose edoxaban regimen 30 mg, and dose-reduced lower dose edoxaban regimen 15 mg
groups, respectively. A greater average percentage of inhibition of endogenous
FXa activity was associated with a lower incidence of ischemic stroke or systemic
embolism and a higher risk of major bleeding ( P<0.001). In a typical subject,
the predicted risks for the 10th and 90th percentiles of inhibition of endogenous
FXa activity were 1.04% and 0.57% for incidence of ischemic stroke or systemic
embolism and 1.35% and 2.33% for major bleeding, respectively. CONCLUSIONS: The
extent of inhibition of endogenous FXa activity is influenced by edoxaban dosing
and clinical characteristics, and it is associated with both antithrombotic
benefit and risk of bleeding. This approach of linking endogenous FXa activity to
clinical outcomes may be used to guide dose selection in future clinical trials,
monitor patients in certain clinical scenarios, or refine the doses of oral FXa
inhibitors in patients who require precise anticoagulation therapy. CLINICAL
TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier:
NCT00781391.
PMID- 29967200
TI - What's happening in Neurology(r)Genetics.
PMID- 29967199
TI - What's happening in Neurology(r)Clinical Practice.
PMID- 29967201
TI - What's happening in Neurology(r)Neuroimmunology & Neuroinflammation.
PMID- 29967202
TI - Spinal myoclonus selectively affecting the platysma after cervical laminectomy.
PMID- 29967203
TI - Pearls & Oy-sters: Alternating hemiplegia of childhood mimics focal epilepsy and
paroxysmal dyskinesia in infancy.
PMID- 29967204
TI - Editors' note: Residency training: The need for an integrated diversity
curriculum for neurology residency.
PMID- 29967205
TI - Reader response: Residency training: The need for an integrated diversity
curriculum for neurology residency.
PMID- 29967206
TI - Editors' note: Infliximab for the treatment of CNS sarcoidosis: A multi
institutional series.
PMID- 29967207
TI - Reader response: Infliximab for the treatment of CNS sarcoidosis: A multi
institutional series.
PMID- 29967208
TI - Author response: Infliximab for the treatment of CNS sarcoidosis: A multi
institutional series.
PMID- 29967209
TI - Clinical Reasoning: A 41-year-old man with thunderclap headache.
PMID- 29967210
TI - Teaching NeuroImages: Presentation of diffuse large B-cell lymphoma with
bilateral sequential oculomotor neuropathy.
PMID- 29967211
TI - Teaching NeuroImages: Distinct visual anosognosia after serial lesions of Meyer
loop and the lateral geniculate body.
PMID- 29967212
TI - An observational study of patients' attitudes to tattoos and piercings on their
physicians: the ART study.
AB - INTRODUCTION: Perceptions regarding body art change over time as societal norms
change. Previous research regarding patients' perceptions of physicians with
exposed body art have been hampered by flaws in design methodology that
incorporate biases into patient responses. This study was performed to determine
whether emergency department (ED) patients perceived a difference in physician
competence, professionalism, caring, approachability, trustworthiness and
reliability in the setting of exposed body art. METHODS: Standardised surveys
about physician competence, professionalism, caring, approachability,
trustworthiness and reliability rating providers on a five point Likert scale
were administered to patients in an ED after an encounter with a physician
provider who demonstrated no body art modification, non-traditional piercings,
tattoos, or both piercings and tattoos. Each provider served as their own
control. Patients were blinded to the purpose of the survey. RESULTS: Patients
did not perceive a difference in physician competence, professionalism, caring,
approachability, trustworthiness or reliability in the setting of exposed body
art. Patients assigned top box performance in all domains >75% of the time,
regardless of physician appearance. CONCLUSION: In the clinical setting, having
exposed body art does not significantly change patients' perception of the
physician.
PMID- 29967215
TI - Targeted Therapy-based Combination Treatment in Rhabdomyosarcoma.
AB - Targeted therapies have revolutionized cancer treatment; however, progress lags
behind in alveolar (ARMS) and embryonal rhabdomyosarcoma (ERMS), a soft-tissue
sarcoma mainly occurring at pediatric and young adult age. Insulin-like growth
factor 1 receptor (IGF1R)-directed targeted therapy is one of the few single
agent treatments with clinical activity in these diseases. However, clinical
effects only occur in a small subset of patients and are often of short duration
due to treatment resistance. Rational selection of combination treatments of
either multiple targeted therapies or targeted therapies with chemotherapy could
hypothetically circumvent treatment resistance mechanisms and enhance clinical
efficacy. Simultaneous targeting of distinct mechanisms might be of particular
interest in this regard, as this affects multiple hallmarks of cancer at once. To
determine the most promising and clinically relevant targeted therapy-based
combination treatments for ARMS and ERMS, we provide an extensive overview of
preclinical and (early) clinical data concerning a variety of targeted therapy
based combination treatments. We concentrated on the most common classes of
targeted therapies investigated in rhabdomyosarcoma to date, including those
directed against receptor tyrosine kinases and associated downstream signaling
pathways, the Hedgehog signaling pathway, apoptosis pathway, DNA damage response,
cell-cycle regulators, oncogenic fusion proteins, and epigenetic modifiers. Mol
Cancer Ther; 17(7); 1365-80. (c)2018 AACR.
PMID- 29967216
TI - Gaining an Easy Visual Grasp on MCP Content.
PMID- 29967214
TI - Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms
and Management Strategies.
AB - Renal cell carcinoma (RCC) is the most common form of kidney cancer. It is
categorized into various subtypes, with clear cell RCC (ccRCC) representing about
85% of all RCC tumors. The lack of sensitivity to chemotherapy and radiation
therapy prompted research efforts into novel treatment options. The development
of targeted therapeutics, including multi-targeted tyrosine kinase inhibitors
(TKI) and mTOR inhibitors, has been a major breakthrough in ccRCC therapy. More
recently, other therapeutic strategies, including immune checkpoint inhibitors,
have emerged as effective treatment options against advanced ccRCC. Furthermore,
recent advances in disease biology, tumor microenvironment, and mechanisms of
resistance formed the basis for attempts to combine targeted therapies with newer
generation immunotherapies to take advantage of possible synergy. This review
focuses on the current status of basic, translational, and clinical studies on
mechanisms of resistance to systemic therapies in ccRCC. Mol Cancer Ther; 17(7);
1355-64. (c)2018 AACR.
PMID- 29967217
TI - Upper rate limits for one-to-one auditory-motor coordination involving whole-body
oscillation: a study of street dancers and non-dancers.
AB - The capacity for auditory-motor coordination (AMC) is shared by several species,
among which humans are most flexible in coordinating with tempo changes. We
investigated how humans lose this tempo flexibility at their upper rate limit,
and the effect of skill level on this phenomenon. Seven skilled street dancers,
including a world champion, and 10 non-dancers were instructed to bend their
knees according to a metronome beat in a standing position at eight constant beat
frequencies (3.8-5 Hz). Although maximum frequency of movement during the task
was 4.8 Hz in the non-dancers and 5.0 Hz in the dancers, the rate limit for AMC
was 4.1 Hz in the non-dancers and 4.9 Hz in the dancers. These results suggest
that the loss of AMC was not due to rate limit of movement execution but rather
to a constraint on the AMC process. In addition, mediation analysis revealed that
a kinematic bias (i.e. the extent of knee flexion during the task) causally
affected the extent of phase wandering via mediating factors (e.g. the extent to
which movement frequency was reduced relative to the beat frequency). These
results add evidence that gravity acts as constraint on AMC involving vertical
rhythmic movement.
PMID- 29967218
TI - Fin and body neuromuscular coordination changes during walking and swimming in
Polypterus senegalus.
AB - The ability to modulate the function of muscle is integral to an animal's ability
to function effectively in the face of widely disparate challenges. This
modulation of function can manifest through short-term changes in neuromuscular
control, but also through long-term changes in force profiles, fatiguability and
architecture. However, the relative extent to which shorter-term modulation and
longer-term plasticity govern locomotor flexibility remains unclear. Here, we
obtain simultaneously recorded kinematic and muscle activity data of fin and body
musculature of an amphibious fish, Polypterus senegalus After examining swimming
and walking behaviour in aquatically raised individuals, we show that walking
behaviour is characterized by greater absolute duration of muscle activity in
most muscles when compared with swimming, but that the magnitude of recruitment
during walking is only increased in the secondary bursts of fin muscle and in the
primary burst of the mid-body point. This localized increase in intensity
suggests that walking in P. senegalus is powered in a few key locations on the
fish, contrasting with the more distributed, low intensity muscle force that
characterizes the stroke cycle during swimming. Finally, the increased intensity
in secondary, but not primary, bursts of the fin muscles when walking probably
underscores the importance of antagonistic muscle activity to prevent fin
collapse, add stabilization and increase body support. Understanding the
principles that underlie the flexibility of muscle function can provide key
insights into the sources of animal functional and behavioural diversity.
PMID- 29967219
TI - Exploring nature's natural knockouts: in vivo cardiorespiratory performance of
Antarctic fishes during acute warming.
AB - We tested the hypothesis that blackfin icefish (Chaenocephalus aceratus), one of
the six species in the family Channichthyidae (the icefishes) that do not express
haemoglobin and myoglobin, lack regulatory cardiovascular flexibility during
acute warming and activity. The experimental protocols were designed to optimize
the surgical protocol and minimize stress. First, minimally invasive heart rate
(fH) measurements were made during a thermal ramp until cardiac failure in C.
aceratus and compared with those from the closely related red-blooded black
rockcod (Notothenia coriiceps). Then, integrative cardiovascular adjustments were
more extensively studied using flow probes and intravascular catheters in C.
aceratus during acute warming (from 0 to 8 degrees C) at rest and after imposed
activity. Chaenocephalus aceratus had a lower routine fH than N. coriiceps (9
beats min-1 versus 14 beats min-1) and a lower peak fH during acute warming (38
beats min-1 versus 55 beats min-1) with a similar cardiac breakpoint temperature
(13 and 14 degrees C, respectively). Routine cardiac output (Q) for C. aceratus
at ~0 degrees C was much lower (26.6 ml min-1 kg-1) than previously reported,
probably because fish in the present study had a low fH (12 beats min-1)
indicative of a high routine vagal tone and low stress. Chaenocephalus aceratus
increased oxygen consumption during acute warming and with activity.
Correspondingly, Q increased considerably (maximally 86.3 ml min-1 kg-1), as did
vascular conductance (5-fold). Thus, unlike earlier suggestions, these data
provide convincing evidence that icefish can mount a well-developed
cardiovascular regulation of heart rate, cardiac output and vascular conductance,
and this regulatory capacity provides flexibility during acute warming.
PMID- 29967220
TI - Optomotor steering and flight control requires a specific sub-section of the
compound eye in the hawkmoth, Manduca sexta.
AB - While tracking odor plumes, male hawkmoths use optic flow cues to stabilize their
flight movements with respect to their environment. We studied the responses of
freely flying moths tracking odor plumes in a laboratory wind tunnel and tethered
moths in an optomotor flight simulator to determine the locations on the compound
eye on which critical optic flow cues are detected. In these behavioral
experiments, we occluded specific regions of the compound eye and systematically
examined the moths' behavior for specific deficits in optic flow processing.
Freely flying moths with the dorsal half of the compound eye painted were unable
to maintain stable flight and track the wind-borne odor plume. However, the plume
tracking performance of moths with the ventral half of their compound eyes
painted was the same as unpainted controls. In a matched set of experiments, we
presented tethered moths with moving vertically oriented sinusoidal gratings and
found that individuals with their eyes unpainted, ventrally painted and medially
painted all responded by attempting optomotor-driven turns in the same
proportion. In contrast, individuals with their compound eyes dorsally painted,
laterally painted and completely painted showed no optomotor turning response. We
decreased the contrast of the visual stimulus and found that this relationship
was consistent down to a contrast level of 2.5%. We conclude that visual input
from the dorso-lateral region of the moth's visual world is critical for
successful maintenance of flight stability and that this species' visual
environment must meet or exceed a contrast ratio of 2.5% to support visual flight
control.
PMID- 29967221
TI - Gamifying Accelerometer Use Increases Physical Activity Levels of Sedentary
Office Workers.
AB - BACKGROUND: Sedentary work is hazardous. Over 80% of all US jobs are
predominantly sedentary, placing full-time office workers at increased risk for
cardiovascular and metabolic morbidity and mortality. Thus, there is a critical
need for effective workplace physical activity interventions. MapTrek is a mobile
health platform that gamifies Fitbit use for the purpose of promoting physical
activity. The purpose of this study was to test the efficacy of MapTrek for
increasing daily steps and moderate-intensity steps over 10 weeks in a sample of
sedentary office workers. METHODS AND RESULTS: Participants included 146 full
time sedentary office workers aged 21 to 65 who reported sitting at least 75% of
their workday. Each participant received a Fitbit Zip to wear daily throughout
the intervention. Participants were randomized to either a: (1) Fitbit-only group
or 2) Fitbit + MapTrek group. Physical activity outcomes and intervention
compliance were measured with the Fitbit activity monitor. The Fitbit + MapTrek
group significantly increased daily steps (+2092 steps per day) and active
minutes (+11.2 min/day) compared to the Fitbit-only arm, but, on average,
participants' steps declined during the study period. CONCLUSIONS: MapTrek is an
effective approach for increasing physical activity at a clinically meaningful
level in sedentary office workers, but as with accelerometer use alone, the
effect decreases over time. CLINICAL TRIAL REGISTRATION: URL:
https://www.clinicaltrials.gov. Unique identifier: NCT03109535.
PMID- 29967224
TI - The Cambridge Analytica affair and Internet-mediated research.
PMID- 29967223
TI - Notch-inducing hydrogels reveal a perivascular switch of mesenchymal stem cell
fate.
AB - The fate of mesenchymal stem cells (MSCs) in the perivascular niche, as well as
factors controlling their fate, is poorly understood. Here, we study MSCs in the
perivascular microenvironment of endothelial capillaries by modifying a synthetic
3D biomimetic poly(ethylene glycol) (PEG)-hydrogel system in vitro We show that
MSCs together with endothelial cells form micro-capillary networks specifically
in soft PEG hydrogels. Transcriptome analysis of human MSCs isolated from
engineered capillaries shows a prominent switch in extracellular matrix (ECM)
production. We demonstrate that the ECM phenotypic switch of MSCs can be
recapitulated in the absence of endothelial cells by functionalizing PEG
hydrogels with the Notch-activator Jagged1. Moreover, transient culture of MSCs
in Notch-inducing microenvironments reveals the reversibility of this ECM switch.
These findings provide insight into the perivascular commitment of MSCs by use of
engineered niche-mimicking synthetic hydrogels.
PMID- 29967226
TI - Circulation Editors and Editorial Board.
PMID- 29967225
TI - Synergistic inactivation of AXL: a (cross)road to cure ovarian cancer?
PMID- 29967227
TI - Are We Ready to Bell The Cat? A Call for Cardiologists to Embrace Glucose
Lowering Therapies Proven to Improve Cardiovascular Outcomes.
PMID- 29967228
TI - Pathways to Cardiorenal Complications in Type 2 Diabetes Mellitus: A Need to
Rethink.
PMID- 29967229
TI - Circulation Global Rounds.
PMID- 29967230
TI - Heart Failure Epidemic: It's Complicated....
PMID- 29967232
TI - Anemia and Iron Deficiency in Heart Failure: Current Concepts and Emerging
Therapies.
AB - Anemia and iron deficiency are important and common comorbidities that often
coexist in patients with heart failure. Both conditions, together or
independently, are associated with poor clinical status and worse outcomes.
Whether anemia and iron deficiency are just markers of heart failure severity or
whether they mediate heart failure progression and outcomes and therefore should
be treated is not entirely clear. Treatment of anemia in patients with heart
failure with erythropoiesis-stimulating agents has been evaluated intensively
during the past several years. Unfortunately, these agents did not improve
outcomes but were associated with a higher risk of adverse events. Iron
deficiency in patients with heart failure can be absolute, when total body iron
is decreased, or functional, when total body iron is normal or increased but is
inadequate to meet the needs of target tissues because of sequestration in the
storage pool. Whereas iron replacement is appropriate in patients with anemia
resulting from absolute iron deficiency, it has been unclear whether and how
absolute or functional iron deficiency should be treated in nonanemic patients
with heart failure. Recently, small studies found that administration of
intravenous iron in patients with heart failure and absolute or functional iron
deficiency with or without anemia improves symptoms and exercise capacity, but
long-term outcomes and safety data are not yet available. In this review, we
discuss the causes and pathogenesis of and treatment options for anemia and iron
deficiency in patients with heart failure.
PMID- 29967231
TI - Understanding Obesity-Related Cardiovascular Disease: It's All About Balance.
PMID- 29967233
TI - Wearable Defibrillator Trial Has Mixed Result.
PMID- 29967234
TI - Highlights From the Circulation Family of Journals.
PMID- 29967235
TI - The Right-Sided ECG for the Right Diagnosis.
PMID- 29967236
TI - Hypogonadism as a Reversible Cause of Torsades de Pointes in Men.
PMID- 29967237
TI - Letter by Yang et al Regarding Article, "Accelerometer-Measured Physical Activity
and Sedentary Behavior in Relation to All-Cause Mortality: The Women's Health
Study".
PMID- 29967238
TI - Response by Lee et al to Letter Regarding Article, "Accelerometer-Measured
Physical Activity and Sedentary Behavior in Relation to All-Cause Mortality: The
Women's Health Study".
PMID- 29967239
TI - Letter by Voicu et al Regarding Article, "Derivation and Validation of the CREST
Model for Very Early Prediction of Circulatory Etiology Death in Patients Without
ST-Segment-Elevation Myocardial Infarction After Cardiac Arrest".
PMID- 29967240
TI - Response by Bascom and Seder to Letter Regarding Article, "Derivation and
Validation of the CREST Model for Very Early Prediction of Circulatory Etiology
Death in Patients Without ST-Segment-Elevation Myocardial Infarction After
Cardiac Arrest".
PMID- 29967241
TI - Letter by Reiffel Regarding Article, "Treatment of Subclinical Atrial
Fibrillation: Does One Plus One Always Equal Two?"
PMID- 29967242
TI - Response by Gold to Letter Regarding Article, "Treatment of Subclinical Atrial
Fibrillation: Does One Plus One Always Equal Two?"
PMID- 29967243
TI - Rac1 nanoscale organization on the plasma membrane is driven by lipid binding
specificity encoded in the membrane anchor.
AB - Rac1 is a small guanine-nucleotide binding protein that cycles between an
inactive GDP-bound and active GTP-bound state to regulate cell motility and
migration. Rac1 signaling is initiated from the plasma membrane (PM). Here we
used high-resolution spatial mapping and manipulation of PM lipid composition to
define Rac1 nanoscale organization. We found that Rac1 in the GTP- and GDP-bound
states assemble into non-overlapping nanoclusters, thus Rac1 proteins undergo
nucleotide-dependent segregation. Rac1 also selectively interacts with
phosphatidic acid (PA) and phosphoinositol (3,4,5)-trisphosphate (PIP3),
resulting in nanoclusters enriched in these lipids. These lipids are structurally
important because depleting the PM of PA or PIP3 impairs both Rac1 PM binding and
Rac1 nanoclustering. Lipid binding specificity of Rac1 is encoded in the amino
acid sequence of the polybasic domain (PBD) of the C-terminal membrane anchor.
Point mutations within the PBD, including arginine to lysine substitutions,
profoundly alter Rac1 lipid binding specificity without changing electrostatics
of the protein, and result in impaired macropinocytosis and decreased cell
spreading. We propose that Rac1 nanoclusters act as lipid based signaling
platforms emulating the spatiotemporal organization of Ras proteins and show that
the Rac1 PBD-prenyl anchor has a biological function that extends beyond simple
electrostatic engagement with the PM.
PMID- 29967244
TI - Histone Chaperone Asf1 Is Required for the Establishment of Repressive Chromatin
in Schizosaccharomyces pombe fbp1 Gene Repression.
AB - The arrangement of nucleosomes in chromatin plays a role in transcriptional
regulation by restricting the accessibility of transcription factors and RNA
polymerase II to cis-acting elements and promoters. For gene activation, the
chromatin structure is altered to an open configuration. The mechanism for this
process has been extensively analyzed. However, the mechanism by which repressive
chromatin is reconstituted to terminate transcription has not been fully
elucidated. Here, we investigated the mechanisms by which chromatin is
reconstituted in the fission yeast Schizosaccharomyces pombefbp1 gene, which is
robustly induced upon glucose starvation but tightly repressed under glucose-rich
conditions. We found that the chromatin structure in the region upstream from
fbp1 is closed by a two-step process. When cells are returned to glucose-rich
medium following glucose starvation, changes in the nucleosome pattern alter the
chromatin configuration at the transcription factor binding site to an
inaccessible state, after which the nucleosome density upstream from fbp1
gradually increases via histone loading. Interestingly, this histone loading was
observed in the absence of the Tup family corepressors Tup11 and Tup12. Analysis
of strains carrying either gene disruptions or mutations affecting nine fission
yeast histone chaperone genes demonstrated that the histone chaperone Asf1
induces nucleosome loading during glucose repression. These data establish a
previously unappreciated chromatin reconstitution mechanism in fbp1 repression.
PMID- 29967245
TI - Heat Shock Causes a Reversible Increase in RNA Polymerase II Occupancy Downstream
of mRNA Genes, Consistent with a Global Loss in Transcriptional Termination.
AB - Cellular transcriptional programs are tightly controlled but can profoundly
change in response to environmental challenges or stress. Here we describe global
changes in mammalian RNA polymerase II (Pol II) occupancy at mRNA genes in
response to heat shock and after recovery from the stress. After a short heat
shock, Pol II occupancy across thousands of genes decreased, consistent with
widespread transcriptional repression, whereas Pol II occupancy increased at a
small number of genes in a manner consistent with activation. Most striking,
however, was loss of the Pol II peak near the 3' ends of mRNA genes, coupled to a
gain in polymerase occupancy extending tens of kilobases downstream of 3' ends.
Typical patterns of 3' end occupancy were largely restored 60 min after cells
returned to normal growth temperatures. These changes in polymerase occupancy
revealed a heat shock-induced loss of normal termination, which was potent,
global, and reversible. The occupancy of the termination factor CPSF73 at the 3'
ends of representative genes was reduced after heat shock, suggesting a mechanism
for impaired termination. The data support a model in which heat shock induces
widespread repression of transcriptional initiation and loss of transcription
termination, which reverses as cells return to homeostasis.
PMID- 29967246
TI - NHS pay should be linked more closely to performance, think tank argues.
PMID- 29967247
TI - Implications of plasma thiol redox in disease.
AB - Thiol groups are crucially involved in signaling/homeostasis through oxidation,
reduction, and disulphide exchange. The overall thiol pool is the resultant of
several individual pools of small compounds (e.g. cysteine), peptides (e.g.
glutathione), and thiol proteins (e.g. thioredoxin (Trx)), which are not in
equilibrium and present specific oxidized/reduced ratios. This review addresses
mechanisms and implications of circulating plasma thiol/disulphide redox pools,
which are involved in several physiologic processes and explored as disease
biomarkers. Thiol pools are regulated by mechanisms linked to their intrinsic
reactivity against oxidants, concentration of antioxidants, thiol-disulphide
exchange rates, and their dynamic release/removal from plasma. Major thiol
couples determining plasma redox potential (Eh) are reduced cysteine
(CyS)/cystine (the disulphide form of cysteine) (CySS), followed by
GSH/disulphide-oxidized glutathione (GSSG). Hydrogen peroxide and hypohalous
acids are the main plasma oxidants, while water-soluble and lipid-soluble small
molecules are the main antioxidants. The thiol proteome and thiol-oxidoreductases
are emerging investigative areas given their specific disease-related responses
(e.g. protein disulphide isomerases (PDIs) in thrombosis). Plasma cysteine and
glutathione redox couples exhibit pro-oxidant changes directly correlated with
ageing/age-related diseases. We further discuss changes in thiol-disulphide redox
state in specific groups of diseases: cardiovascular, cancer, and
neurodegenerative. These results indicate association with the disease states,
although not yet clear-cut to yield specific biomarkers. We also highlight
mechanisms whereby thiol pools affect atherosclerosis pathophysiology. Overall,
it is unlikely that a single measurement provides global assessment of plasma
oxidative stress. Rather, assessment of individual thiol pools and thiol-proteins
specific to any given condition has more solid and logical perspective to yield
novel relevant information on disease risk and prognosis.
PMID- 29967248
TI - A Combination of Approved Antibodies Overcomes Resistance of Lung Cancer to
Osimertinib by Blocking Bypass Pathways.
AB - Purpose: Because of emergence of resistance to osimertinib, a third-generation
EGFR tyrosine kinase inhibitor (TKI), no targeted treatments are available for
patients with lung cancer who lose sensitivity due to new mutations or bypass
mechanisms. We examined in animals and in vitro an alternative therapeutic
approach making use of antibodies.Experimental Design: An osimertinib-sensitive
animal model of lung cancer, which rapidly develops drug resistance, has been
employed. To overcome compensatory hyperactivation of ERK, which we previously
reported, an anti-EGFR antibody (cetuximab) was combined with other antibodies,
as well as with a subtherapeutic dose of osimertinib, and cancer cell apoptosis
was assayed.Results: Our animal studies identified a combination of three
clinically approved drugs, cetuximab, trastuzumab (an anti-HER2 mAb), and
osimertinib (low dose), as an effective and long-lasting treatment that is able
to prevent onset of resistance to osimertinib. A continuous schedule of
concurrent treatment was sufficient for effective tumor inhibition and for
prevention of relapses. Studies employing cultured cells and analyses of tumor
extracts indicated that the combination of two mAbs and a subtherapeutic TKI dose
sorted EGFR and HER2 for degradation; cooperatively enhanced apoptosis; inhibited
activation of ERK; and reduced abundance of several bypass proteins, namely MET,
AXL, and HER3.Conclusions: Our in vitro assays and animal studies identified an
effective combination of clinically approved drugs that might overcome resistance
to irreversible TKIs in clinical settings. The results we present attribute the
long-lasting effect of the drug combination to simultaneous blockade of several
well-characterized mechanisms of drug resistance. Clin Cancer Res; 24(22); 5610
21. (c)2018 AACR See related commentary by Fan and Yu, p. 5499.
PMID- 29967250
TI - Dynamics of Genome Alterations in Crohn's Disease-Associated Colorectal
Carcinogenesis.
AB - Purpose: Patients with inflammatory bowel diseases, that is, ulcerative colitis
and Crohn's disease (CD), face an increased risk of developing colorectal cancer
(CRC). Evidence, mainly from ulcerative colitis, suggests that TP53 mutations
represent an initial step in the progression from inflamed colonic epithelium to
CRC. However, the pathways involved in the evolution of CRC in patients with CD
are poorly characterized.Experimental Design: Here, we analyzed 73 tissue samples
from 28 patients with CD-CRC, including precursor lesions, by targeted next
generation sequencing of 563 cancer-related genes and array-based comparative
genomic hybridization. The results were compared with 24 sporadic CRCs with
similar histomorphology (i.e., mucinous adenocarcinomas), and to The Cancer
Genome Atlas data (TCGA).Results: CD-CRCs showed somatic copy-number alterations
(SCNAs) similar to sporadic CRCs with one notable exception: the gain of 5p was
significantly more prevalent in CD-CRCs. CD-CRCs had a distinct mutation
signature: TP53 (76% in CD-CRCs vs. 33% in sporadic mucinous CRCs), KRAS (24% vs.
50%), APC (17% vs. 75%), and SMAD3 (3% vs. 29%). TP53 mutations and SCNAs were
early and frequent events in CD progression, while APC, KRAS, and SMAD2/4
mutations occurred later. In four patients with CD-CRC, at least one mutation
and/or SCNAs were already present in non-dysplastic colonic mucosa, indicating
occult tumor evolution.Conclusions: Molecular profiling of CD-CRCs and precursor
lesions revealed an inflammation-associated landscape of genome alterations: 5p
gains and TP53 mutations occurred early in tumor development. Detection of these
aberrations in precursor lesions may help predicting disease progression and
distinguishes CD-associated from sporadic colorectal neoplasia. Clin Cancer Res;
24(20); 4997-5011. (c)2018 AACR.
PMID- 29967249
TI - The Anticancer Activity of a First-in-class Small-molecule Targeting PCNA.
AB - PURPOSE: Proliferating cell nuclear antigen (PCNA) plays an essential role in
regulating DNA synthesis and repair and is indispensable to cancer cell growth
and survival. We previously reported a novel cancer associated PCNA isoform
(dubbed caPCNA), which was ubiquitously expressed in a broad range of cancer
cells and tumor tissues, but not significantly in nonmalignant cells. We found
the L126-Y133 region of caPCNA is structurally altered and more accessible to
protein-protein interaction. A cell-permeable peptide harboring the L126-Y133
sequence blocked PCNA interaction in cancer cells and selectively kills cancer
cells and xenograft tumors. On the basis of these findings, we sought small
molecules targeting this peptide region as potential broad-spectrum anticancer
agents. EXPERIMENTAL DESIGN: By computer modeling and medicinal chemistry
targeting a surface pocket partly delineated by the L126-Y133 region of PCNA, we
identified a potent PCNA inhibitor (AOH1160) and characterized its therapeutic
properties and potential toxicity. RESULTS: AOH1160 selectively kills many types
of cancer cells at below micromolar concentrations without causing significant
toxicity to a broad range of nonmalignant cells. Mechanistically, AOH1160
interferes with DNA replication, blocks homologous recombination-mediated DNA
repair, and causes cell-cycle arrest. It induces apoptosis in cancer cells and
sensitizes them to cisplatin treatment. AOH1160 is orally available to animals
and suppresses tumor growth in a dosage form compatible to clinical applications.
Importantly, it does not cause significant toxicity at 2.5 times of an effective
dose. CONCLUSIONS: These results demonstrated the favorable therapeutic
properties and the potential of AOH1160 as a broad-spectrum therapeutic agent for
cancer treatment.
PMID- 29967251
TI - Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation
and Enhances Glioma Radiosensitivity.
AB - Purpose: Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)
targeted therapies in glioma. We hypothesized that inhibition of protein N-linked
glycosylation, an endoplasmic reticulum co- and posttranslational modification
crucial for RTK maturation and activation, could provide a new therapeutic
approach for glioma radiosensitization.Experimental Design: We investigated the
effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on
EGFR family receptors, MET, PDGFR, and FGFR1. The influence of glycosylation
state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA
damage, and cell-cycle arrest were determined and correlated with glioma cell
receptor expression profiles. The effects of NGI-1 on xenograft tumor growth were
tested using a nanoparticle formulation validated by in vivo molecular imaging. A
mechanistic role for RTK signaling was evaluated through the expression of a
glycosylation-independent CD8-EGFR chimera.Results: NGI-1 reduced glycosylation,
protein levels, and activation of most RTKs. NGI-1 also enhanced the
radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with
elevated ErbB family activation, but not in cells without high levels of RTK
activation. NGI-1 radiosensitization was associated with increases in both DNA
damage and G1 cell-cycle arrest. Combined treatment of glioma xenografts with
fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared
with controls. Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1
arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as
the principal mechanism for the NGI-1 effect.Conclusions: This study suggests
that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to
radiosensitize malignant gliomas with enhanced RTK signaling. Clin Cancer Res; 1
12. (c)2018 AACR.
PMID- 29967252
TI - CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy
Protocols.
AB - Purpose: Noninvasive and quantitative tracking of CD8+ T cells by PET has emerged
as a potential technique to gauge response to immunotherapy. We apply an anti-CD8
cys-diabody, labeled with 64Cu, to assess the sensitivity of PET imaging of
normal and diseased tissue.Experimental Design: Radiolabeling of an anti-CD8 cys
diabody (169cDb) with 64Cu was developed. The accumulation of 64Cu-169cDb was
evaluated with PET/CT imaging (0, 5, and 24 hours) and biodistribution (24 hours)
in wild-type mouse strains (n = 8/group studied with imaging and IHC or flow
cytometry) after intravenous administration. Tumor-infiltrating CD8+ T cells in
tumor-bearing mice treated with CpG and alphaPD-1 were quantified and mapped (n =
6-8/group studied with imaging and IHC or flow cytometry).Results: We demonstrate
the ability of immunoPET to detect small differences in CD8+ T-cell distribution
between mouse strains and across lymphoid tissues, including the intestinal tract
of normal mice. In FVB mice bearing a syngeneic HER2-driven model of mammary
adenocarcinoma (NDL), 64Cu-169cDb PET imaging accurately visualized and
quantified changes in tumor-infiltrating CD8+ T cells in response to
immunotherapy. A reduction in the circulation time of the imaging probe followed
the development of treatment-related liver and splenic hypertrophy and provided
an indication of off-target effects associated with immunotherapy
protocols.Conclusions: 64Cu-169cDb imaging can spatially map the distribution of
CD8+ T cells in normal organs and tumors. ImmunoPET imaging of tumor-infiltrating
cytotoxic CD8+ T cells detected changes in T-cell density resulting from adjuvant
and checkpoint immunotherapy protocols in our preclinical evaluation. Clin Cancer
Res; 24(20); 4976-87. (c)2018 AACR.
PMID- 29967254
TI - Cheng MP, Pandit A, Antin JH, et al. Safety and immunogenicity of conjugate
quadrivalent meningococcal vaccination after hematopoietic cell transplantation.
Blood Adv. 2018;2(11):1272-1276.
PMID- 29967253
TI - High-Throughput Functional Evaluation of Variants of Unknown Significance in
ERBB2.
AB - Purpose: The advent of next-generation sequencing technologies has enabled the
identification of several activating mutations of Erb-B2 receptor tyrosine kinase
2 (ERBB2) among various cancers. However, the significance of infrequent
mutations has not been fully investigated. Herein, we comprehensively assessed
the functional significance of the ERBB2 mutations in a high-throughput
manner.Experimental Design: We evaluated the transforming activities and drug
sensitivities of 55 nonsynonymous ERBB2 mutations using the mixed-all-nominated
in-one (MANO) method.Results: G776V, G778_S779insG, and L841V were newly revealed
to be activating mutations. Although afatinib, neratinib, and osimertinib were
shown to be effective against most of the ERBB2 mutations, only osimertinib
demonstrated good efficacy against L755P and L755S mutations, the most common
mutations in breast cancer. In contrast, afatinib and neratinib were predicted to
be more effective than other inhibitors for the A775_776insYVMA mutation, the
most frequent ERBB2 mutation in lung cancer. We surveyed the prevalence of
concurrent ERBB2 mutation with gene amplification and found that approximately
30% of ERBB2-amplified urothelial carcinomas simultaneously carried ERBB2
mutations, altering their sensitivity to trastuzumab, an mAb against ERBB2.
Furthermore, the MANO method was applied to evaluate the functional significance
of 17 compound mutations within ERBB2 reported in the COSMIC database, revealing
that compound mutations involving L755S were sensitive to osimertinib but
insensitive to afatinib and neratinib.Conclusions: Several ERBB2 mutations showed
varying sensitivities to ERBB2-targeted inhibitors. Our comprehensive assessment
of ERBB2 mutations offers a fundamental database to help customize therapy for
ERBB2-driven cancers.We identified several ERBB2 mutations as activating
mutations related to tumorigenesis. In addition, our comprehensive evaluation
revealed that several ERBB2 mutations showed varying sensitivities to ERBB2
targeted inhibitors, and thus, the functional significance of each variant should
be interpreted precisely to design the best treatment for each patient. Clin
Cancer Res; 24(20); 5112-22. (c)2018 AACR.
PMID- 29967255
TI - A B-cell-associated gene signature classification of diffuse large B-cell
lymphoma by NanoString technology.
AB - Gene expression profiling (GEP) by microarrays of diffuse large B-cell lymphoma
(DLBCL) has enabled the categorization of DLBCL into activated B-cell-like and
germinal center B-cell-like subclasses. However, as this does not fully embrace
the great diversity of B-cell subtypes, we recently developed a gene expression
assay for B-cell-associated gene signature (BAGS) classification. To facilitate
quick and easy-to-use BAGS profiling, we developed in this study the NanoString
based BAGS2Clinic assay. Microarray data from 4 different cohorts (n = 970) were
used to select genes and train the assay. The locked assay was validated in an
independent cohort of 88 sample biopsies. The assay showed good correspondence
with the original BAGS classifier, with an overall accuracy of 84% (95%
confidence interval, 72% to 93%) and a subtype-specific accuracy ranging between
80% and 99%. BAGS classification has the potential to provide valuable insight
into tumor biology as well as differences in resistance to immuno- and
chemotherapy that can lead to novel treatment strategies for DLBCL patients.
BAGS2Clinic can facilitate this and the implementation of BAGS classification as
a routine clinical tool to improve prognosis and treatment guidance for DLBCL
patients.
PMID- 29967257
TI - Microenvironmental Cues Determine Tumor Cell Susceptibility to Neutrophil
Cytotoxicity.
AB - We have recently shown that neutrophil antitumor cytotoxicity is Ca2+ dependent
and is mediated by TRPM2, an H2O2-dependent Ca2+ channel. However, neutrophil
antitumor activity is dependent on context and is manifested in the premetastatic
niche, but not at the primary site. We therefore hypothesized that expression of
TRPM2 and the consequent susceptibility to neutrophil cytotoxicity may be
associated with the epithelial/mesenchymal cellular state. We found that TRPM2
expression was upregulated during epithelial-to-mesenchymal transition (EMT), and
mesenchymal cells were more susceptible to neutrophil cytotoxicity. Conversely,
cells undergoing mesenchymal-to-epithelial transition (MET) expressed reduced
levels of TRPM2, rendering them resistant to neutrophil cytotoxicity. Cells
expressing reduced levels of TRPM2 were protected from neutrophil cytotoxicity
and seeded more efficiently in the premetastatic lung. These data identify TRPM2
as the link between environmental cues at the primary tumor site, tumor cell
susceptibility to neutrophil cytotoxicity, and disease progression. Furthermore,
these data identify EMT as a process enhancing tumor-cell immune susceptibility
and, by contrast, MET as a novel mode of immune evasion.Significance: EMT is
required for metastatic spread and concomitantly enhances tumor cell
susceptibility to neutrophil cytotoxicity. Cancer Res; 78(17); 5050-9. (c)2018
AACR.
PMID- 29967256
TI - Expression of Long Noncoding RNA YIYA Promotes Glycolysis in Breast Cancer.
AB - Long noncoding RNA (lncRNA) is yet to be linked to cancer metabolism. Here, we
report that upregulation of the lncRNA LINC00538 (YIYA) promotes glycolysis, cell
proliferation, and tumor growth in breast cancer. YIYA is associated with the
cytosolic cyclin-dependent kinase CDK6 and regulated CDK6-dependent
phosphorylation of the fructose bisphosphatase PFK2 (PFKFB3) in a cell-cycle
independent manner. In breast cancer cells, these events promoted catalysis of
glucose 6-phosphate to fructose-2,6-bisphosphate/fructose-1,6-bisphosphate.
CRISPR/Cas9-mediated deletion of YIYA or CDK6 silencing impaired glycolysis and
tumor growth in vivo In clinical specimens of breast cancer, YIYA was expressed
in approximately 40% of cases where it correlated with CDK6 expression and
unfavorable survival outcomes. Our results define a functional role for lncRNA in
metabolic reprogramming in cancer, with potential clinical implications for its
therapeutic targeting.Significance: These findings offer a first glimpse into how
a long-coding RNA influences cancer metabolism to drive tumor growth. Cancer Res;
78(16); 4524-32. (c)2018 AACR.
PMID- 29967258
TI - PDSS2 Deficiency Induces Hepatocarcinogenesis by Decreasing Mitochondrial
Respiration and Reprogramming Glucose Metabolism.
AB - Glucose metabolic reprogramming from oxidative phosphorylation to glycolysis is
one of the hallmarks of cancer development. Coenzyme Q10 (CoQ10) is essential for
electron transport in the mitochondrial respiratory chain and for antioxidant
defense. Here, we investigated the role of a key factor in CoQ10 synthesis,
prenyldiphosphate synthase subunit 2 (PDSS2), in hepatocellular carcinoma (HCC)
tumorigenesis. PDSS2 was frequently downregulated in HCC tissues and was
significantly associated with poorer HCC prognosis (P = 0.027). PDSS2
downregulation was a prognostic factor independent of T status and stage (P =
0.028). Downregulation of CoQ10 was significantly correlated with downregulation
of PDSS2 in HCC tumor tissues (R = 0.414; P < 0.001). Of the six different
splicing isoforms of PDSS2, the five variants other than full-length PDSS2 showed
loss of function in HCC. Reintroduction of full-length PDSS2 into HCC cells
increased CoQ10 and mitochondrial electron transport complex I activity and
subsequently induced a metabolic shift from aerobic glycolysis to mitochondrial
respiration in cells. Reintroduction of PDSS2 also inhibited foci formation,
colony formation in soft agar, and tumor formation in nude mice. Knockdown of
PDSS2 induced chromosomal instability in the MIHA immortalized human liver cell
line. Furthermore, knockdown of PDSS2 in MIHA induced malignant transformation.
Overall, our findings indicate that PDSS2 deficiency might be a novel driving
factor in HCC development.Significance: Downregulation of PDSS2 is a driving
factor in hepatocellular carcinoma tumorigenesis. Cancer Res; 78(16); 4471-81.
(c)2018 AACR.
PMID- 29967259
TI - Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates Mutual Regulation of
Their Immunosuppressive Effects in the Tumor Microenvironment.
AB - Recently emerging cancer immunotherapies combine the applications of therapeutics
to disrupt the immunosuppressive conditions in tumor-bearing hosts. In this
study, we found that targeting the proinflammatory cytokine IL6 enhances tumor
specific Th1 responses and subsequent antitumor effects in tumor-bearing mice.
IL6 blockade upregulated expression of the immune checkpoint molecule programmed
death-ligand 1 (PD-L1) on melanoma cells. This PD-L1 induction was canceled in
IFNgamma-deficient mice or CD4+ T cell-depleted mice, suggesting that CD4+ T cell
derived IFNgamma is important for PD-L1 induction in tumor-bearing hosts. In some
patients with melanoma, however, treatment with the anti-PD-1 antibody nivolumab
increased systemic levels of IL6, which was associated with poor clinical
responses. This PD-L1 blockade-evoked induction of IL6 was reproducible in
melanoma-bearing mice. We found that PD-1/PD-L1 blockade prompted PD-1+
macrophages to produce IL6 in the tumor microenvironment. Depletion of
macrophages in melanoma-bearing mice reduced the levels of IL6 during PD-L1
blockade, suggesting macrophages are responsible for the IL6-mediated defective
CD4+ Th1 response. Combined blockade of the mutually regulated immunosuppressive
activities of IL6 and PD-1/PD-L1 signals enhanced expression of T cell-attracting
chemokines and promoted infiltration of IFNgamma-producing CD4+ T cells in tumor
tissues, exerting a synergistic antitumor effect, whereas PD-L1 blockade alone
did not promote Th1 response. Collectively, these findings suggest that IL6 is a
rational immunosuppressive target for overcoming the narrow therapeutic window of
anti-PD-1/PD-L1 therapy.Significance: These findings advance our understanding of
IL6-PD1/PD-L1 cross-talk in the tumor microenvironment and provide clues for
targeted interventional therapy that may prove more effective against cancer.
Cancer Res; 78(17); 5011-22. (c)2018 AACR.
PMID- 29967261
TI - CRISPR/Cas9-Mediated Knockout of DGK Improves Antitumor Activities of Human T
Cells.
AB - The efficacy of T-cell therapy is inhibited by various tumor-associated
immunosuppressive ligands and soluble factors. Such inhibitory signals turn
specific T-cell signaling pathways on or off, impeding the anticancer functions
of T cells. Many studies have focused on PD-1 or CTLA-4 blockade to invigorate T
cell functions through CD28/B7 signaling, but obtaining robust clinical outcomes
remains challenging. In this study, we use CRISPR/Cas9 to potentiate T-cell
function by increasing CD3 signaling via knockout of diacylglycerol kinase (DGK),
an enzyme that metabolizes diacylglycerol to phosphatidic acid. Knockout of DGK
augmented the effector functions of CAR-T cells in vitro via increased TCR
signaling. DGK knockout from CAR-T cells rendered them resistant to soluble
immunosuppressive factors such as TGFbeta and prostaglandin E2 and sustained
effector functions under conditions of repeated tumor stimulation. Moreover, DGK
knockout caused significant regression of U87MGvIII glioblastoma tumors through
enhanced effector functions in a xenograft mouse model. Collectively, our study
shows that knockout of DGK effectively enhances the effector functions of CAR-T
cells, suggesting that CRISPR/Cas9-mediated knockout of DGK could be applicable
as part of a multifaceted clinical strategy to treat solid cancers.Significance:
This novel study demonstrates efficient ablation of diacylglycerol kinase in
human CAR-T cells that leads to improved antitumor immunity and may have
significant impact in human cancer immunotherapy. Cancer Res; 78(16); 4692-703.
(c)2018 AACR.
PMID- 29967260
TI - Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared
Fluorescence.
AB - For many solid tumors, surgical resection remains the gold standard and tumor
involved margins are associated with poor clinical outcomes. Near-infrared (NIR)
fluorescence imaging using molecular agents has shown promise for in situ imaging
during resection. However, for cancers with difficult imaging conditions,
surgical value may lie in tumor mapping of surgical specimens. We thus evaluated
a novel approach for real-time, intraoperative tumor margin assessment. Twenty
one adult patients with biopsy-confirmed squamous cell carcinoma arising from the
head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled.
Cohort 1 (n = 3) received panitumumab-IRDye800CW at an intravenous microdose of
0.06 mg/kg, cohort 2A (n = 5) received 0.5 mg/kg, cohort 2B (n = 7) received 1
mg/kg, and cohort 3 (n = 6) received 50 mg. Patients were followed 30 days
postinfusion and adverse events were recorded. Imaging was performed using
several closed- and wide-field devices. Fluorescence was histologically
correlated to determine sensitivity and specificity. In situ imaging demonstrated
tumor-to-background ratio (TBR) of 2 to 3, compared with ex vivo specimen imaging
TBR of 5 to 6. We obtained clear differentiation between tumor and normal tissue,
with a 3-fold signal difference between positive and negative specimens (P <
0.05). We achieved high correlation of fluorescence intensity with tumor location
with sensitivities and specificities >89%; fluorescence predicted distance of
tumor tissue to the cut surface of the specimen. This novel method of detecting
tumor-involved margins in surgical specimens using a cancer-specific agent
provides highly sensitive and specific, real-time, intraoperative surgical
navigation in resections with complex anatomy, which are otherwise less amenable
to image guidance.Significance: This study demonstrates that fluorescence can be
used as a sensitive and specific method of guiding surgeries for head and neck
cancers and potentially other cancers with challenging imaging conditions,
increasing the probability of complete resections and improving oncologic
outcomes. Cancer Res; 78(17); 5144-54. (c)2018 AACR.
PMID- 29967262
TI - CircNT5E Acts as a Sponge of miR-422a to Promote Glioblastoma Tumorigenesis.
AB - Circular RNA and long noncoding RNA function as efficient miRNA sponges that
regulate gene expression in eukaryotes. However, the sponges of functional miRNAs
in glioblastoma remain largely unknown. Here, we identify a subset of circRNAs
and lncRNAs that are specifically increased in miR-422a-downregulated
glioblastoma tissues. We characterized a novel circRNA derived from NT5E, named
circNT5E, that is regulated by ADARB2 binding to sites flanking circRNA-forming
introns. We hypothesized that circNT5E may serve as a sponge against miR-422a in
glioblastoma tumorigenesis. circNT5E controlled multiple pathologic processes,
including cell proliferation, migration, and invasion. circNT5E directly bound
miR-422a and inhibited miR-422a activity. Furthermore, circNT5E was observed to
sponge other miRNAs, exhibiting tumor suppressor-like features in glioblastoma.
Taken together, these findings highlight a novel oncogenic function of circRNA in
glioblastoma tumorigenesis.Significance: Microarray profiling of
circRNA/lncRNA/mRNA in glioblastoma identifies circNT5E as an oncogenic circular
RNA and a sponge of miR-422a. Cancer Res; 78(17); 4812-25. (c)2018 AACR.
PMID- 29967263
TI - High-Throughput Screening of Combinatorial Immunotherapies with Patient-Specific
In Silico Models of Metastatic Colorectal Cancer.
AB - Solid tumors are rich ecosystems of numerous different cell types whose
interactions lead to immune escape and resistance to immunotherapy in virtually
all patients with metastatic cancer. Here, we have developed a 3D model of human
solid tumor tissue that includes tumor cells, fibroblasts, and myeloid and
lymphoid immune cells and can represent over a million cells over clinically
relevant timeframes. This model accurately reproduced key features of the tissue
architecture of human colorectal cancer and could be informed by individual
patient data, yielding in silico tumor explants. Stratification of growth
kinetics of these explants corresponded to significantly different overall
survival in a cohort of patients with metastatic colorectal cancer. We used the
model to simulate the effect of chemotherapy, immunotherapies, and cell migration
inhibitors alone and in combination. We classified tumors according to tumor and
host characteristics, showing that optimal treatment strategies markedly differed
between these classes. This platform can complement other patient-specific ex
vivo models and can be used for high-throughput screening of combinatorial
immunotherapies.Significance: This patient-informed in silico tumor growth model
allows testing of different cancer treatment strategies and immunotherapies on a
cell/tissue level in a clinically relevant scenario. Cancer Res; 78(17); 5155-63.
(c)2018 AACR.
PMID- 29967264
TI - CTGF Mediates Tumor-Stroma Interactions between Hepatoma Cells and Hepatic
Stellate Cells to Accelerate HCC Progression.
AB - Connective tissue growth factor (CTGF) is a matricellular protein related to
hepatic fibrosis. This study aims to clarify the roles of CTGF in hepatocellular
carcinoma (HCC), which usually develops from fibrotic liver. CTGF was
overexpressed in 93 human HCC compared with nontumorous tissues, primarily in
tumor cells. Increased CTGF expression was associated with clinicopathologic
malignancy of HCC. CTGF was upregulated in hepatoma cells in hepatocyte-specific
Kras-mutated mice (Alb-Cre KrasLSL-G12D/+). Hepatocyte-specific knockout of CTGF
in these mice (Alb-Cre KrasLSL-G12D/+ CTGFfl/fl) decreased liver tumor number and
size. Hepatic stellate cells (HSC) were present in both human and murine liver
tumors, and alpha-SMA expression, a marker of HSC activation, positively
correlated with CTGF expression. Forced expression of CTGF did not affect growth
of PLC/PRF/5 cells, a hepatoma cell line with little CTGF expression, but
facilitated their growth in the presence of LX-2 cells, an HSC line. The growth
of HepG2 cells, which express high levels of CTGF, was promoted by coculture with
LX-2 cells compared with monoculture. Growth promotion by LX-2 cells was negated
by an anti-CTGF antibody in both culture and xenografts. Coculturing LX-2 cells
with HepG2 cells drove LX-2-derived production of IL6, which led to STAT-3
activation and proliferation of HepG2 cells. An anti-CTGF antibody reduced IL6
production in LX-2 cells and suppressed STAT-3 activation in HepG2 cells. In
conclusion, our data identify tumor cell-derived CTGF as a keystone in the HCC
microenvironment, activating nearby HSC that transmit progrowth signals to HCC
cells, and this interaction is susceptible to inhibition by an anti-CTGF
antibody.Significance: Protumor cross-talk between cancer cells and hepatic
stellate cells presents an opportunity for therapeutic intervention against
HCC.Graphical Abstract:
http://cancerres.aacrjournals.org/content/canres/78/17/4902/F1.large.jpg Cancer
Res; 78(17); 4902-14. (c)2018 AACR.
PMID- 29967265
TI - Inhibition of Rspo-Lgr4 Facilitates Checkpoint Blockade Therapy by Switching
Macrophage Polarization.
AB - Therapies targeting immune checkpoints have shown great clinical potential in a
subset of patients with cancer but may be hampered by a failure to reverse the
immunosuppressive tumor microenvironment (TME). As the most abundant immune cells
in TME, tumor-associated macrophages (TAM) play nonredundant roles in restricting
antitumor immunity. The leucine-rich repeat-containing G-protein-coupled receptor
4 (Lgr4, also known as Gpr48) has been associated with multiple physiologic and
pathologic functions. Lgr4 and its ligands R-spondin 1-4 have been shown to
promote the growth and metastasis of tumor cells. However, whether Lgr4 can
promote tumor progression by regulating the function of immune cells in the tumor
microenvironment remains largely unknown. Here, we demonstrate that Lgr4 promotes
macrophage M2 polarization through Rspo/Lgr4/Erk/Stat3 signaling. Notably,
urethane-induced lung carcinogenesis, Lewis lung carcinoma (LLC), and B16F10
melanoma tumors were all markedly reduced in Lgr4fl/flLyz2cre/+ mice,
characterized by fewer protumoral M2 TAMs and increased CD8+ T lymphocyte
infiltration in the TME. Furthermore, LLC tumor growth was greatly depressed when
Rspo/Lgr4/Erk/Stat3 signaling was blocked with either the LGR4 extracellular
domain or an anti-Rspo1 antibody. Importantly, blocking Rspo-Lgr4 signaling
overcame LLC resistance to anti-PD-1 therapy and improved the efficacy of PD-1
immunotherapy against B16F10 melanoma, indicating vital roles of Rspo-Lgr4 in
host antitumor immunity and a potential therapeutic target in cancer
immunotherapy.Significance: This study identifies a novel receptor as a critical
switch in TAM polarization whose inhibition sensitizes checkpoint therapy
resistant lung cancer to anti-PD-1 therapy.Graphical Abstract:
http://cancerres.aacrjournals.org/content/canres/78/17/4929/F1.large.jpg Cancer
Res; 78(17); 4929-42. (c)2018 AACR.
PMID- 29967266
TI - Why do models of insect respiratory patterns fail?
AB - Insects exchange respiratory gases using an astonishing diversity of patterns. Of
these, discontinuous gas exchange cycles (DGCs) have received the most study, but
there are many other patterns exhibited intraspecifically and interspecifically.
Moreover, some individual insects transition between patterns based on poorly
understood combinations of internal and external factors. Why have biologists
failed, so far, to develop a framework capable of explaining this diversity?
Here, we propose two answers. The first is that the framework will have to be
simultaneously general and highly detailed. It should describe, in a universal
way, the physical and chemical processes that any insect uses to exchange gases
through the respiratory system (i.e. tracheal tubes and spiracles) while
simultaneously containing enough morphological, physiological and neural detail
that it captures the specifics of patterns exhibited by any species or
individual. The second difficulty is that the framework will have to provide
ultimate, evolutionary explanations for why patterns vary within and among
insects as well as proximate physiological explanations for how different parts
of the respiratory system are modified to produce that diversity. Although
biologists have made significant progress on all of these problems individually,
there has been little integration among approaches. We propose that renewed
efforts be undertaken to integrate across levels and approaches with the goal of
developing a new class of general, flexible models capable of explaining a
greater fraction of the observed diversity of respiratory patterns.
PMID- 29967268
TI - Correction: Low-resolution vision in a velvet worm (Onychophora) (doi:
10.1242/jeb.175802).
PMID- 29967267
TI - Eco-immunology in the cold: the role of immunity in shaping the overwintering
survival of ectotherms.
AB - The effect of temperature on physiology mediates many of the challenges that
ectotherms face under climate change. Ectotherm immunity is thermally sensitive
and, as such, environmental change is likely to have complex effects on survival,
disease resistance and transmission. The effects of temperature on immunity will
be particularly profound in winter because cold and overwintering are important
triggers and regulators of ectotherm immune activity. Low temperatures can both
suppress and activate immune responses independent of parasites, which suggests
that temperature not only affects the rate of immune responses but also provides
information that allows overwintering ectotherms to balance investment in
immunity and other physiological processes that underlie winter survival.
Changing winter temperatures are now shifting ectotherm immunity, as well as the
demand for energy conservation and protection against parasites. Whether an
ectotherm can survive the winter will thus depend on whether new immune
phenotypes will shift to match the conditions of the new environment, or leave
ectotherms vulnerable to infection or energy depletion. Here, we synthesise
patterns of overwintering immunity in ectotherms and examine how new winter
conditions might affect ectotherm immunity. We then explore whether it is
possible to predict the effects of changing winter conditions on ectotherm
vulnerability to the direct and indirect effects of parasites.
PMID- 29967269
TI - Preparation of In Vitro-Transcribed RNA for Microinjection.
AB - Perhaps the most crucial step for success in microinjection of RNAs is the
preparation of the in vitro-transcribed RNA.
PMID- 29967270
TI - Microinjection of RNA into Mouse Zygotes.
AB - This protocol describes the injection of RNA into zygotes.
PMID- 29967271
TI - Generating Yeast One-Hybrid DNA-Bait Strains.
AB - Generating DNA-bait strains for gateway-compatible yeast one-hybrid (Y1H) screens
involves three steps. The first is to generate an Entry clone containing the DNA
bait of interest. Gateway cloning is used to clone larger baits, such as
promoters, into pDONR-P4-P1R. (An alternative set of steps is also presented in
this protocol that describes the creation of Entry clones by annealing primers
and performing conventional ligation into pMW#5-a strategy best suited for
smaller DNA-baits up to 100 bp.) The second is to transfer this DNA-bait from the
Entry clone to the two Y1H reporter Destination vectors, pMW#2 (HIS3) and pMW#3
(LacZ). A two-step process is used because Entry clones generate a versatile
resource that can be used for transfer of DNA-baits into a variety of vectors,
for instance, upstream of the green fluorescent protein-encoding ORF to study
spatiotemporal expression patterns. The final step is to integrate the HIS3 and
LacZ reporter constructs into the genome of the Y1H yeast strain, YM4271. The
entire process takes 24-32 d, plus sequence confirmation if necessary.
PMID- 29967272
TI - Generating Yeast Two-Hybrid Bait Strains.
AB - Generating DNA-binding domain (DB)-bait strains for Gateway-compatible yeast two
hybrid (Y2H) screens involves three steps. The first is to generate an Entry
clone containing a DNA fragment encoding the protein of interest (e.g., an open
reading frame, ORF). The second is to transfer this DNA fragment from the Entry
clone to the Y2H Destination vector, pDEST32. The final step is to transform this
construct into the Y2H yeast strain, MaV103. This protocol takes 24-37 d plus
sequence confirmation, if necessary, to complete.
PMID- 29967274
TI - High-Efficiency Yeast Transformation.
AB - High-efficiency yeast transformation is used for integrations into YM4271 (yeast
one-hybrid (Y1H) DNA-bait generation), for transforming libraries of activation
domain (AD)-prey clones into Y1H and yeast two-hybrid (Y2H)-bait strains, and for
gap repair. The protocol takes 2 d to complete.
PMID- 29967273
TI - Identifying Interactors from an Activation Domain Prey Library.
AB - In yeast hybrid assays, the process of identifying preys that interact with the
bait of interest involves several steps. First, in this protocol, the bait yeast
strain is transformed with a library of activation domain (AD)-prey clones and
plated on selective media containing 3-aminotriazole (3AT). This selects
transformants containing an AD-prey clone that induces HIS3 reporter expression.
Second, these "HIS-positive" colonies are analyzed for LacZ induction (and,
optionally, URA3 induction in yeast two-hybrid (Y2H) assays). Third, yeast PCR is
used on these "double-positive" colonies to amplify the insert from the AD-prey
plasmid. Fourth, some of this PCR product is used to perform a gap-repair retest
to confirm the interaction in fresh bait-strain yeast, and the remainder is used
for DNA sequencing to determine prey identity for those that successfully retest.
Finally, interactions are carefully examined to filter out likely false-positive
interactions. This protocol takes 20-43 d plus sequence confirmation to complete.
PMID- 29967275
TI - Transfection Mediated by DEAE-Dextran.
AB - Here, we describe two variations on the classical DEAE-dextran transfection
procedure. The first involves a brief exposure of cells to a high concentration
of DEAE-dextran and yields higher transfection frequencies but elevated cellular
toxicity. The second involves a longer exposure of cells to a lower concentration
of DEAE-dextran, which produces lower transfection frequencies but increased cell
survival.
PMID- 29967276
TI - Preparing Whole-Cell Lysates for Immunoblotting.
AB - In this protocol, adherent cells are grown in tissue culture dishes until ready
to be used for protein sample preparation. To analyze proteins by immunoblotting,
it is necessary to bring the proteins from the sample into soluble form using the
buffers, salts, and detergents compatible with the gel electrophoresis procedure.
If a protein sample is being prepared for immunoblotting only, the proteins can
be solubilized using sodium dodecyl sulfate polyacrylamide gel electrophoresis
(SDS-PAGE) sample loading buffer, as described in this protocol, which ensures
rapid and efficient extraction of most cellular proteins because of the presence
of SDS, a strong anionic detergent. SDS-PAGE sample loading buffer denatures
proteins and disrupts the bonds between the proteins that interact with each
other. Therefore, this lysis technique can be detrimental to the applications
when the native structure of the protein is essential, including enzymatic
activity assays and analysis of protein-protein interactions.
PMID- 29967277
TI - Preparing Protein Solutions for Immunoblotting.
AB - Most protein solutions can be mixed with sample buffer and analyzed directly by
immunoblotting. Any protein extraction buffer or solvent that is compatible with
gel electrophoresis can be used for preparing samples for immunoblotting.
Examples of the protein solutions suitable for immunoblotting include purified
proteins, detergent lysates of cells, samples prepared by subcellular
fractionation, and protein eluates from chromatography columns. The protein of
interest must be sufficiently abundant in the sample to allow for efficient
detection, but the total amount of protein in the sample should not exceed the
loading capacity of the gel. For this reason, protein antigens of very low
abundance must be partially purified from the protein mixtures containing high
concentrations of the contaminating proteins. In this protocol, solutions
containing the protein antigens of interest are mixed with SDS-PAGE sample buffer
and boiled to prepare samples for protein gel electrophoresis.
PMID- 29967278
TI - Gateway-Compatible Yeast One-Hybrid and Two-Hybrid Assays.
AB - In the first section of this introduction, we provide background information for
yeast two-hybrid (Y2H) assays that provide a genetic method for the
identification and analysis of binary protein-protein interactions and that are
complementary to biochemical methods such as immunoprecipitation. In the second
section, we discuss yeast one-hybrid (Y1H) assays that provide a "gene-centered"
(DNA-to-protein) genetic method to identify and study protein-DNA interactions
between cis-regulatory elements and transcription factors (TFs). This method is
complementary to "TF-centered" (protein-to-DNA) biochemical methods such as
chromatin immunoprecipitation.
PMID- 29967279
TI - DEAE-Dextran Transfection.
AB - Biochemical methods of transfection, including calcium phosphate-mediated and
diethylaminoethyl (DEAE)-dextran-mediated transfection, have been used for many
years to deliver nucleic acids into cultured eukaryotic cells. Here, we briefly
review the use of DEAE-dextran in transfection.
PMID- 29967280
TI - Shedding of CD16 disassembles the NK cell immune synapse and boosts serial
engagement of target cells.
AB - Natural Killer (NK) cells can engage multiple virally infected or tumor cells
sequentially and deliver perforin for cytolytic killing of these targets. Using
microscopy to visualize degranulation from individual NK cells, we found that
repeated activation via the Fc receptor CD16 decreased the amount of perforin
secreted. However, perforin secretion was restored upon subsequent activation via
a different activating receptor, NKG2D. Repeated stimulation via NKG2D also
decreased perforin secretion, but this was not rescued by stimulation via CD16.
These different outcomes of sequential stimulation could be accounted for by
shedding of CD16 being triggered by cellular activation. The use of
pharmacological inhibitors and NK cells transfected to express a noncleavable
form of CD16 revealed that CD16 shedding also increased NK cell motility and
facilitated detachment of NK cells from target cells. Disassembly of the immune
synapse caused by CD16 shedding aided NK cell survival and boosted serial
engagement of target cells. Thus, counterintuitively, shedding of CD16 may
positively impact immune responses.
PMID- 29967282
TI - Cytokinin signalling regulates organ identity via the AHK4 receptor in
Arabidopsis.
AB - Mutual interactions of the phytohormones, cytokinins and auxin determine root or
shoot identity during postembryonic de novo organogenesis in plants. However, our
understanding of the role of hormonal metabolism and perception during early
stages of cell fate reprogramming is still elusive. Here we show that auxin
activates root formation, whereas cytokinins mediate early loss of the root
identity, primordia disorganisation and initiation of shoot development.
Exogenous and endogenous cytokinins influence the initiation of newly formed
organs, as well as the pace of organ development. The process of de novo shoot
apical meristem establishment is accompanied by accumulation of endogenous
cytokinins, differential regulation of genes for individual cytokinin receptors,
strong activation of AHK4-mediated signalling and induction of the shoot-specific
homeodomain regulator WUSCHEL. The last is associated with upregulation of
isopentenyladenine-type cytokinins, revealing higher shoot-forming potential when
compared with trans-zeatin. Moreover, AHK4-controlled cytokinin signalling
negatively regulates the root stem cell organiser WUSCHEL RELATED HOMEOBOX 5 in
the root quiescent centre. We propose an important role for endogenous cytokinin
biosynthesis and AHK4-mediated cytokinin signalling in the control of de novo
induced organ identity.
PMID- 29967281
TI - SP8 and SP9 coordinately promote D2-type medium spiny neuron production by
activating Six3 expression.
AB - Dopamine receptor DRD1-expressing medium spiny neurons (D1 MSNs) and dopamine
receptor DRD2-expressing medium spiny neurons (D2 MSNs) are the principal
projection neurons in the striatum, which is divided into dorsal striatum
(caudate nucleus and putamen) and ventral striatum (nucleus accumbens and
olfactory tubercle). Progenitors of these neurons arise in the lateral ganglionic
eminence (LGE). Using conditional deletion, we show that mice lacking the
transcription factor genes Sp8 and Sp9 lose virtually all D2 MSNs as a result of
reduced neurogenesis in the LGE, whereas D1 MSNs are largely unaffected. SP8 and
SP9 together drive expression of the transcription factor Six3 in a spatially
restricted domain of the LGE subventricular zone. Conditional deletion of Six3
also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants.
Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative
enhancer of Six3 Thus, this study defines components of a transcription pathway
in a regionally restricted LGE progenitor domain that selectively drives the
generation of D2 MSNs.
PMID- 29967284
TI - Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing
Autosomal Dominant Tubulointerstitial Kidney Disease.
AB - BACKGROUND: Autosomal dominant tubulointerstitial kidney disease caused by mucin
1 gene (MUC1) mutations (ADTKD-MUC1) is characterized by progressive kidney
failure. Genetic evaluation for ADTKD-MUC1 specifically tests for a cytosine
duplication that creates a unique frameshift protein (MUC1fs). Our goal was to
develop immunohistochemical methods to detect the MUC1fs created by the cytosine
duplication and, possibly, by other similar frameshift mutations and to identify
novel MUC1 mutations in individuals with positive immunohistochemical staining
for the MUC1fs protein. METHODS: We performed MUC1fs immunostaining on urinary
cell smears and various tissues from ADTKD-MUC1-positive and -negative controls
as well as in individuals from 37 ADTKD families that were negative for mutations
in known ADTKD genes. We used novel analytic methods to identify MUC1 frameshift
mutations. RESULTS: After technique refinement, the sensitivity and specificity
for MUC1fs immunostaining of urinary cell smears were 94.2% and 88.6%,
respectively. Further genetic testing on 17 families with positive MUC1fs
immunostaining revealed six families with five novel MUC1 frameshift mutations
that all predict production of the identical MUC1fs protein. CONCLUSIONS: We
developed a noninvasive immunohistochemical method to detect MUC1fs that, after
further validation, may be useful in the future for diagnostic testing.
Production of the MUC1fs protein may be central to the pathogenesis of ADTKD
MUC1.
PMID- 29967285
TI - MCD1 Associates with FtsZ Filaments via the Membrane-Tethering Protein ARC6 to
Guide Chloroplast Division.
AB - Chloroplasts replicate by binary fission, a process driven by ring-like dynamic
division machinery at mid-chloroplast. In Arabidopsis thaliana, the first
molecular assembly of this machinery, the Z-ring, forms via the association of
FtsZ1 and FtsZ2 heteropolymers with the inner envelope membrane through the
membrane-tethering protein ACCUMULATION AND REPLICATION OF CHLOROPLASTS6 (ARC6).
Spatial control of Z-ring assembly ensures the correct placement of the division
machinery and, therefore, symmetric chloroplast division. The plant-specific
protein MULTIPLE CHLOROPLAST DIVISION SITE1 (MCD1) plays a role in Z-ring
positioning and chloroplast division site placement, but its mechanism of action
is unknown. Here, we provide evidence that MCD1 is a bitopic inner membrane
protein whose C terminus faces the chloroplast stroma. Interaction analysis
showed that MCD1 and ARC6 directly interact in the stroma and that MCD1 binds to
FtsZ2 in an ARC6-dependent manner. These results are consistent with the in vivo
observation that ARC6 influences the localization of MCD1 to membrane-tethered
FtsZ filaments. Additionally, we found that MCD1 is required for the regulation
of Z-ring positioning by ARC3 and MinE1, two components of the chloroplast Min
(minicell) system, which negatively regulates Z-ring placement. Together, our
findings indicate that MCD1 is part of the chloroplast Min system that recognizes
membrane-tethered FtsZ filaments during chloroplast division-ring positioning.
PMID- 29967286
TI - Genome-Wide Association Analyses Reveal the Importance of Alternative Splicing in
Diversifying Gene Function and Regulating Phenotypic Variation in Maize.
AB - Alternative splicing (AS) enhances transcriptome diversity and plays important
roles in regulating plant processes. Although widespread natural variation in AS
has been observed in plants, how AS is regulated and contribute to phenotypic
variation is poorly understood. Here, we report a population-level transcriptome
assembly and genome-wide association study to identify splicing quantitative
trait loci (sQTLs) in developing maize (Zea mays) kernels from 368 inbred lines.
We detected 19,554 unique sQTLs for 6570 genes. Most sQTLs showed small isoform
usage changes without involving major isoform switching between genotypes. The
sQTL-affected isoforms tend to display distinct protein functions. We demonstrate
that nonsense-mediated mRNA decay, microRNA-mediated regulation, and small
interfering peptide-mediated peptide interference are frequently involved in sQTL
regulation. The natural variation in AS and overall mRNA level appears to be
independently regulated with different cis-sequences preferentially used. We
identified 214 putative trans-acting splicing regulators, among which ZmGRP1,
encoding an hnRNP-like glycine-rich RNA binding protein, regulates the largest
trans-cluster. Knockout of ZmGRP1 by CRISPR/Cas9 altered splicing of numerous
downstream genes. We found that 739 sQTLs colocalized with previous marker-trait
associations, most of which occurred without changes in overall mRNA level. Our
findings uncover the importance of AS in diversifying gene function and
regulating phenotypic variation.
PMID- 29967287
TI - Discovery of UDP-Glycosyltransferases and BAHD-Acyltransferases Involved in the
Biosynthesis of the Antidiabetic Plant Metabolite Montbretin A.
AB - Plant specialized metabolism serves as a rich resource of biologically active
molecules for drug discovery. The acylated flavonol glycoside montbretin A (MbA)
and its precursor myricetin 3-O-(6'-O-caffeoyl)-glucosyl rhamnoside (mini-MbA)
are potent inhibitors of human pancreatic alpha-amylase and are being developed
as drug candidates to treat type-2 diabetes. MbA occurs in corms of the
ornamental plant montbretia (Crocosmia x crocosmiiflora), but a system for large
scale MbA production is currently unavailable. Biosynthesis of MbA from the
flavonol myricetin and MbA accumulation occur during early stages of corm
development. We established myricetin 3-O-rhamnoside (MR), myricetin 3-O-glucosyl
rhamnoside (MRG), and mini-MbA as the first three intermediates of MbA
biosynthesis. Contrasting the transcriptomes of young and old corms revealed
differentially expressed UDP-sugar-dependent glycosyltransferases (UGTs) and BAHD
acyltransferases (BAHD-ATs). UGT77B2 and UGT709G2 catalyze the consecutive
glycosylation of myricetin to produce MR and of MR to give MRG, respectively. In
addition, two BAHD-ATs, CcAT1 and CcAT2, catalyze the acylation of MRG to
complete the formation of mini-MbA. Transcript profiles of UGT77B2, UGT709G2,
CcAT1, and CcAT2 during corm development matched the metabolite profile of MbA
accumulation. Expression of these enzymes in wild tobacco (Nicotiana benthamiana)
resulted in the formation of a surrogate mini-MbA, validating the potential for
metabolic engineering of mini-MbA in a heterologous plant system.
PMID- 29967288
TI - Comparison of Oryza sativa and Oryza brachyantha Genomes Reveals Selection-Driven
Gene Escape from the Centromeric Regions.
AB - Centromeres are dynamic chromosomal regions, and the genetic and epigenetic
environment of the centromere is often regarded as oppressive to protein-coding
genes. Here, we used comparative genomic and phylogenomic approaches to study the
evolution of centromeres and centromere-linked genes in the genus Oryza We report
a 12.4-Mb high-quality BAC-based pericentromeric assembly for Oryza brachyantha,
which diverged from cultivated rice (Oryza sativa) ~15 million years ago. The
synteny analyses reveal seven medium (>50 kb) pericentric inversions in O. sativa
and 10 in O. brachyantha Of these inversions, three resulted in centromere
movement (Chr1, Chr7, and Chr9). Additionally, we identified a potential
centromere-repositioning event, in which the ancestral centromere on chromosome
12 in O. brachyantha jumped ~400 kb away, possibly mediated by a duplicated
transposition event (>28 kb). More strikingly, we observed an excess of syntenic
gene loss at and near the centromeric regions (P < 2.2 * 10-16). Most (33/47) of
the missing genes moved to other genomic regions; therefore such excess could be
explained by the selective loss of the copy in or near centromeric regions after
gene duplication. The pattern of gene loss immediately adjacent to centromeric
regions suggests centromere chromatin dynamics (e.g., spreading or
microrepositioning) may drive such gene loss.
PMID- 29967289
TI - Identifying a missing lineage driver in a subset of lung neuroendocrine tumors.
AB - Tumor heterogeneity of a primary histologic cancer type has major implications
for cancer research and therapeutics. An important and understudied aspect of
this heterogeneity is the role of transcription factors that serve as "lineage
oncogenes" in a tumor type. A demonstration that different subgroups have
distinct dependencies on lineage-specific transcription factors is highlighted in
a relatively homogenous cancer type: the pulmonary neuroendocrine cancer small
cell lung carcinoma (SCLC). Identification of these factors is providing new
insights into the origin of the heterogeneity and subtype-specific
vulnerabilities in SCLC and provides a template for studying heterogeneity in
other cancer types.
PMID- 29967290
TI - SCAMP4 enhances the senescent cell secretome.
AB - The senescence-associated secretory phenotype (SASP) is a major trait of
senescent cells, but the molecular regulators of SASP factor secretion are poorly
understood. Mass spectrometry analysis revealed that secretory carrier membrane
protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent
cells compared with proliferating cells. Interestingly, silencing SCAMP4 in
senescent fibroblasts reduced the secretion of SASP factors, including
interleukin 6 (IL6), IL8, growth differentiation factor 15 (GDF-15), C-X-C motif
chemokine ligand 1 (CXCL1), and IL7, while, conversely, SCAMP4 overexpression in
proliferating fibroblasts increased SASP factor secretion. Our results indicate
that SCAMP4 accumulates on the surface of senescent cells, promotes SASP factor
secretion, and critically enhances the SASP phenotype.
PMID- 29967291
TI - Polymerase pausing induced by sequence-specific RNA-binding protein drives
heterochromatin assembly.
AB - In Schizosaccharomyces pombe, transcripts derived from the pericentromeric dg and
dh repeats promote heterochromatin formation via RNAi as well as an RNAi
independent mechanism involving the RNA polymerase II (RNAPII)-associated RNA
binding protein Seb1 and RNA processing activities. We show that Seb1 promotes
long-lived RNAPII pauses at pericentromeric repeat regions and that their
presence correlates with the heterochromatin-triggering activities of the
corresponding dg and dh DNA fragments. Globally increasing RNAPII stalling by
other means induces the formation of novel large ectopic heterochromatin domains.
Such ectopic heterochromatin occurs even in cells lacking RNAi. These results
uncover Seb1-mediated polymerase stalling as a signal necessary for
heterochromatin nucleation.
PMID- 29967293
TI - Umbelliferone alleviates hepatic injury in diabetic db/db mice via inhibiting
inflammatory response and activating Nrf2-mediated antioxidant.
AB - The current study was designed to investigate the protective effect and possible
mechanisms of umbelliferone (Umb) on liver injury in diabetic C57BL/KsJ-db/db
(dbdb) mice. Mice were divided into five groups: wild-type mice group (WY), dbdb
mice group, dbdb mice + Metformin (100 mg/kg) group, dbdb mice + Umb (20, 40
mg/kg) group. Blood glucose regulation was assessed by an oral glucose tolerance
test (OGTT). At 28 days after drug administration, blood samples were obtained
for the analysis of lipids and enzymes related to hepatic function, including
alanine aminotransferase (ALT), aspartate aminotransaminase (AST) and total
cholesterol (TC) and triglyceride (TG). Expression levels of inflammatory
cytokines (TNF-alpha, IL-1beta, and IL-6) and oxidative stress indicators (SOD
and MDA) were measured with ELISA kit. The expressions of high-mobility group box
1 (HMGB1), Toll-like receptor (TLR) 4 (TLR4), Myd88, NF-kappaB, IkappaB, Nrf2,
and HO-1 proteins were also evaluated by Western blotting analysis. The results
showed that Umb significantly restored the blood glucose in OGTT, and inhibited
the levels of insulin, TG, TC, as well as activities of ALT and AST. Moreover,
Umb inhibited diabetic inflammation through down-regulating the expression of
HMGB1, TLR4, NF-kappaB, and IkappaB. In addition, Umb alleviated oxidative damage
in the liver by activating Nrf2-mediated signal pathway. These findings
demonstrated that Umb exhibited protective effect against diabetic live injury,
which may be through inhibiting HMGB1-induced inflammatory response and
activating Nrf2-mediated antioxidant.
PMID- 29967292
TI - Endoreduplication of the mouse genome in the absence of ORC1.
AB - The largest subunit of the origin recognition complex (ORC1) is essential for
assembly of the prereplicative complex, firing of DNA replication origins, and
faithful duplication of the genome. Here, we generated knock-in mice with LoxP
sites flanking exons encoding the critical ATPase domain of ORC1. Global or
tissue-specific ablation of ORC1 function in mouse embryo fibroblasts and fetal
and adult diploid tissues blocked DNA replication, cell lineage expansion, and
organ development. Remarkably, ORC1 ablation in extraembryonic trophoblasts and
hepatocytes, two polyploid cell types in mice, failed to impede genome
endoreduplication and organ development and function. Thus, ORC1 in mice is
essential for mitotic cell divisions but dispensable for endoreduplication. We
propose that DNA replication of mammalian polyploid genomes uses a distinct ORC1
independent mechanism.
PMID- 29967294
TI - TUG1 promotes prostate cancer progression by acting as a ceRNA of miR-26a.
AB - Previous studies have demonstrated that taurine-upregulated gene 1 (TUG1) was
aberrantly expressed and involved in multiple types of cancer; however, the
expression profile and potential role of TUG1 in prostate cancer (PCa) remains
unclear. The aim of the present study was to evaluate the expression and function
of TUG1 in PCa. In the present study, we analyzed TUG1 expression levels of PCa
patients in tumor and adjacent normal tissue by real-time quantitative PCR.
Knockdown of TUG1 by RNAi was performed to explore its roles in cell
proliferation, migration, and invasion. Here we report, for the first time, that
TUG1 promotes tumor cell migration, invasion, and proliferation in PCa by working
in key aspects of biological behaviors. TUG1 could negatively regulate the
expression of miR-26a in PCa cells. The bioinformatics prediction revealed
putative miR-26a-binding sites within TUG1 transcripts. In conclusion, our study
suggests that long non-coding RNA (lncRNA) TUG1 acts as a functional oncogene in
PCa development.
PMID- 29967297
TI - Correction: Synergistic Interaction between the HDAC Inhibitor, MPT0E028, and
Sorafenib in Liver Cancer Cells In Vitro and In Vivo.
PMID- 29967295
TI - APOL1 risk variants cause podocytes injury through enhancing endoplasmic
reticulum stress.
AB - Two coding sequence variants (G1 and G2) of Apolipoprotein L1 (APOL1) gene have
been implicated as a higher risk factor for chronic kidney diseases (CKD) in
African Americans when compared with European Americans. Previous studies have
suggested that the APOL1 G1 and G2 variant proteins are more toxic to kidney
cells than the wild-type APOL1 G0, but the underlying mechanisms are poorly
understood. To determine whether endoplasmic reticulum (ER) stress contributes to
podocyte toxicity, we generated human podocytes (HPs) that stably overexpressed
APOL1 G0, G1, or G2 (Vec/HPs, G0/HPs, G1/HPs, and G2/HPs). Propidium iodide
staining showed that HP overexpressing the APOL1 G1 or G2 variant exhibited a
higher rate of necrosis when compared with those overexpressing the wild-type G0
counterpart. Consistently, the expression levels of nephrin and podocin proteins
were significantly decreased in the G1- or G2-overexpressing cells despite the
maintenance of their mRNA expressions levels. In contrast, the expression of the
78-kDa glucose-regulated protein ((GRP78), also known as the binding Ig protein,
BiP) and the phosphorylation of the eukaryotic translation initiation factor 1
(eIF1) were significantly elevated in the G1/HPs and G2/HPs, suggesting a
possible occurrence of ER stress in these cells. Furthermore, ER stress
inhibitors not only restored nephrin protein expression, but also provided
protection against necrosis in G1/HPs and G2/HPs, suggesting that APOL1 risk
variants cause podocyte injury partly through enhancing ER stress.
PMID- 29967298
TI - Interdisciplinary approaches for uncovering the impacts of architecture on
collective behaviour.
AB - Built structures, such as animal nests or buildings that humans occupy, serve two
overarching purposes: shelter and a space where individuals interact. The former
has dominated much of the discussion in the literature. But, as the study of
collective behaviour expands, it is time to elucidate the role of the built
environment in shaping collective outcomes. Collective behaviour in social
animals emerges from interactions, and collective cognition in humans emerges
from communication and coordination. These collective actions have vast economic
implications in human societies and critical fitness consequences in animal
systems. Despite the obvious influence of space on interactions, because spatial
proximity is necessary for an interaction to occur, spatial constraints are
rarely considered in studies of collective behaviour or collective cognition. An
interdisciplinary exchange between behavioural ecologists, evolutionary
biologists, cognitive scientists, social scientists, architects and engineers can
facilitate a productive exchange of ideas, methods and theory that could lead us
to uncover unifying principles and novel research approaches and questions in
studies of animal and human collective behaviour. This article, along with those
in this theme issue aims to formalize and catalyse this interdisciplinary
exchange.This article is part of the theme issue 'Interdisciplinary approaches
for uncovering the impacts of architecture on collective behaviour'.